PMID- 8855619
TI  - Transmural migration of a retained surgical sponge into the intestinal lumen: an
      experimental study.
AB  - A retained surgical sponge in the peritoneal cavity is an occasional misadventure
      in modern surgery. Such a sponge can migrate into the intestinal lumen, but its
      mechanism is still unknown. A piece of surgical sponge, measuring 4 x 4
      centrimetres, was placed at different sites of the abdominal cavity of Wistar
      rats. Inspite of the absence of infection, entry of the sponge into the
      intestinal lumen was shown microscopically in 10 out of 36 rats. Parallel
      statistical analysis by Cutler-Ederer estimation was found to be 0.58 of
      condition probability at 6 months. Transmural migration of a retained surgical
      sponge was not only associated with different sites placing in the abdominal
      cavity (P = 0.680), but also whether a seromuscular incision was made or not (P =
      0.306). A hypothesis, based on a study of microscopic and macroscopic pathology,
      is proposed as four stages: foreign body reaction, secondary infection, mass
      formation and remodeling.

PMID- 8855620
TI  - Evaluation of colposcopic accuracy in diagnosis of cervical neoplasia.
AB  - OBJECTIVE: To evaluate the accuracy of colposcopy in the diagnosis of cervical
      neoplasia. STUDY DESIGN: A four year retrospective study from May, 1991 to May
      1995 was conducted in 309 patients with abnormal cervical cytology who had
      undergone colposcopic examination at the Mc Cormick Hospital. The correlation
      between cervical cytology and colposcopically directed biopsy (CDB), colposcopic
      impression and CDB, CDB and subsequent conization or hysterectomy specimens were
      analyzed. The correlation was accepted as accurate when both reports were either
      the same or within one-step disparity of pathologic diagnosis and no invasive
      cancer was missed. RESULTS: In comparison of cervical cytology and CDB, the
      correlation was accurate in 212 of 241 cases (88%). The CDB was found to be less
      and more severe than cytology in 16 cases (6.6%) and 13 cases (5.4%)
      respectively. Colposcopic impression was accurate in 221 of 241 patients (91.7%)
      when compared to the CDB results. Sixty nine patients had undergone conization.
      The results of the CDB were comparable with those of the conization specimens in
      all but 8 patients, giving a total accuracy of 88.4 per cent. Four cases of
      invasive cancer were missed at the time of colposcopy and biopsy but subsequently
      diagnosed by conization. Of 67 patients who underwent hysterectomy, the surgical
      specimens were found to be more advanced than CDB in 4 patients, giving a total
      accuracy of 94 per cent. Two cases of minimally microinvasive cancer were missed.
      CONCLUSION: This study confirms the diagnostic value of colposcopy in the
      management of patients with abnormal cervical cytology.

PMID- 8855621
TI  - Clinical efficacy of itraconazole with initial flucytosine in AIDS-related
      cryptococcal meningitis: a preliminary study.
AB  - This open, prospective study systematically examined the clinical efficacy of
      itraconazole and initial flucytosine in AIDS-associated cryptococcal meningitis.
      Clinical as well as mycological responses were evaluated in 10 patients.
      Satisfactory outcome was achieved in 8 patients (cure in 4 and improvement in 4).
      In all, 5 patients died, three as a result of cryptococcal meningitis. The
      remaining 5 patients have been followed for 5-12 months. The treatment proved to
      be well-tolerated and safe.

PMID- 8855622
TI  - Factors associated with one-year mortality of the Thai elderly living in a
      community.
AB  - A prospective study that aimed to identify the risk factors of one-year mortality
      among 703 Thai elderly living in a community was conducted. High age, having no
      work, low Barthel ADL index score, low Chula ADL index score and high OPCS
      disability score are univariate risk factors of death. Having no work and low BAI
      score were independent risk factors identified by logistic regression analysis
      using survival status as the dependent factor. Direct effect of working on
      mortality is suggested from the result of the study.

PMID- 8855623
TI  - Randomized trial radiotherapy with and without concomitant 13-cis-retinoic acid
      plus interferon-alpha for locally advanced cervical cancer: a preliminary report.
AB  - Locally advanced cervical cancer could be treated with Interferon-alpha plus
      retinoic acid concomitant with standard radiotherapy. It showed some response in
      local control. The pattern of relapse and the survival of the patients should be
      observed in the follow-up period for the conclusion.

PMID- 8855624
TI  - Radiofrequency ablation of cardiac arrhythmia: the first fifty cases experience
      in Siriraj Hospital.
AB  - In our series of 50 consecutive patients with a wide variety of cardiac
      arrhythmia, a combined approach to electrophysiological diagnosis and definitive
      treatment with catheter ablation was associated with a high degree of efficacy,
      low procedural complication and low rate of arrhythmia recurrence. The
      radiofrequency catheter ablation should be considered as the acceptable or
      preferable first line treatment in patients with supraventricular tachycardia and
      idiopathic ventricular tachycardia.

PMID- 8855625
TI  - Effectiveness of percutaneous transluminal coronary angioplasty for patients with
      unstable angina.
AB  - We have reported a series of patients with unstable angina successfully treated
      with PTCA. It can be performed safely with a high success rate in a selected
      population.

PMID- 8855626
TI  - A study of 111 cases of globus hystericus.
AB  - Videofluorography (VFG) and manometry were used to evaluate 111 patients who were
      diagnosed with globus hystericus. Most of the globus patients were affected by
      functional diseases and the underlying pathology could be revealed by VFG in 73.9
      per cent of the series and by manometry in 80.2 per cent. There were 10.8 per
      cent of the series in which VFG and manometry yieled normal findings. The most
      common abnormality determined by manometry was esophageal aperistalsis. The most
      common abnormality revealed by VFG was cricopharyngeal bar. VFG was sensitive for
      morphologic detection while manometry was sensitive for motility study.
      Functional disorders can result in morphologic abnormality and vice versa.
      Therefore, VFG and manometry complement each other and are invaluable tools in
      the investigation of globus patients.

PMID- 8855627
TI  - A study of the prevalence of and risk factors for ear diseases and hearing loss
      in primary school children in Hat Yai, Thailand.
AB  - 2,184 primary school children in Hat Yai Municipality, Southern Thailand were
      screened for ear diseases and hearing loss using screening audiometry, portable
      tympanometry and otoscopy to identify children with possible ear problems, 754
      children failed the initial screen, 728 were retested and a group of 243 were
      referred for ENT examination and standard audiometry-tympanometry. Children with
      hearing loss and otitis media were thus identified. A questionnaire to identify
      possible risk factors was administered. The prevalence of otitis media in this
      population was found to be 3.25 per cent (AOM 0.69%, OME 1.14%, COM 1.74%). No
      risk factor identified as significant were found. Non-significant factors
      included sex, age, URI last month, father smoking, mother smoking and method of
      transport to school as an indication of social status. This study contrasts with
      a previous study in 1990 which showed a 3.5 per cent prevalence of COM.

PMID- 8855628
TI  - Segawa disease.
AB  - A 14-year-old girl with Segawa disease is reported. The dystonic movement began
      at the age of three and slow progressive deterioration followed. The girl became
      bed-ridden and required assistance for all activities of daily living. Diurnal
      fluctuation and sleep benefit was clearly observed. Inheritence appears to be
      autosomal dominant. A dramatic, immediate and sustained response to L-dopa
      therapy was noted. This disorder is a form of treatable dystonia in childhood and
      adolescence and it is recommended that patients in this age group with primary
      dystonia should be given a trial of low dose L-dopa even though they have a
      chronic course or severe disability.

PMID- 8855629
TI  - Pulmonary infections in HIV infected patients.
AB  - We retrospectively reviewed causes, clinical presentations and chest radiographs
      of pulmonary infections in symptomatic HIV infected patients diagnosed in
      Srinagarind Hospital from February 1992 to 1994. We found 95 episodes of
      pulmonary infections in 88 HIV infected patients enrolled in our review. The
      three most common pathogens were Mycobacterium tuberculosis (37.2%), Pneumocystis
      carinii (23.8%), and Cryptococcus (15.2%). Coexistent pulmonary infections were
      seen in 10.5 per cent, mostly due to P. carinii and Cryptococcus neoformans.
      Extrapulmonary infections were also common, particularly with M. tuberculosis
      (49%) and C. neoformans (100%). The common clinical presentations were fever,
      dyspnea, and cough which frequency varied among the organisms. Chest radiographs
      were nonspecific, the most common finding was bilateral pulmonary infiltrates
      except that bacterial pneumonia usually presented with unilateral infiltrates.
      All patients wit PC had significant hypoxia (PaO2 < 70 mmHg). Due to nonspecific
      clinical and chest film presentations as well as frequent coinfections, definite
      diagnosis should be carried out in all HIV infected patients with pulmonary
      infections.

PMID- 8855630
TI  - Topical analgesics, indomethacin plaster and diclofenac emulgel for low back
      pain: a parallel study.

PMID- 8855631
TI  - First trimester prenatal diagnosis by transcervical chorionic villus sampling
      using curved biopsy forceps: lessons of the first 30 continuing pregnancies.
AB  - Transcervical chorionic villus sampling was performed on 30 pregnancies who were
      at risk for chromosomal abnormalities between 9 and 12 weeks of gestation to
      determine whether the developing fetus had a chromosomal disorder. Curved biopsy
      forceps were passed transcervically into the chorion frondosum under continuous
      real-time ultrasound guidance, and chorionic villi were biopsied. Chorion yield
      was assessed semiquantitatively. An adequate villus sample was obtained in all
      cases, giving a success rate of 100 per cent. The average weight of the villi was
      18.8 mg with a lower limit of 10 mg which proved sufficient for diagnostic
      purposes. The villi were processed for chromosomal analyses by cultured
      preparations. A diagnostic result was achieved in 28 of cases (93.3%) within 2
      weeks. No major maternal complications were encountered. The fetal loss rate was
      3.3 per cent. No fetal anomalies were found in the study group. It is concluded
      that transcervical chorionic villus sampling appears to be a relatively safe and
      reliable procedure, but the risk of miscarriage can only be accurately assessed
      after further investigation. In contrast to amniocentesis, the procedure is
      performed early in pregnancy and results of the genetic test are available during
      the first trimester. We believe that transcervical chorionic villus sampling
      offers an alternative to amniocentesis in the detection of genetic disorders.

PMID- 8855632
TI  - Serum vitamin D, parathyroid hormone and biochemical markers of bone turnover in
      normal Thai subjects.
AB  - The sera from 158 healthy Thai volunteers (77 males and 81 females), aged 20-80
      years, were studied. The vitamin D status, parathyroid gland activity and the
      magnitude of bone turnover were assessed by measurement of serum 25
      hydroxycholecalciferol (25-OH-D), intact parathyroid hormone (N-tact-PTH),
      osteocalcin and alkaline phosphatase. The mean serum 25-OH-D, N-tact-PTH,
      osteocalcin and alkaline phosphatase concentrations in men were 67.4 +/- 31.6
      (S.D.) [Range (R): 20.6-147.1 ng/ml], 23.3 +/- 10.3 (R: 5.6-56.6 pg/ml) 3.4 +/-
      1.5 (R: 1.2-10.5 ng/ml), and 19.9 +/- 6.6 (R: 7.5-35.7 IU/L), respectively, and
      the mean levels in women were 42.4 +/- 23.9 (R: 13.8-127.8 ng/ml), 26.1 +/- 11.3
      (R: 10.5-68.7 pg/ml), 3.7 +/- 2.1 (R: 0.5-11.5 ng/ml), and 19.5 +/- 6.0 (R: 9.1
      41.5 IU/L), respectively. There is no evidence of vitamin D deficiency in
      ambulatory elderly Thais. Serum N-tact PTH increased with advancing age in both
      men and women whereas increasing serum osteocalcin and alkaline phosphatase with
      age were observed only in women. In addition, serum alkaline phosphatase
      correlated to serum osteocalcin only in women suggesting an increase in bone
      turnover after menopause. These basic data would be useful for the study of
      metabolic bone diseases in Thai population.

PMID- 8855633
TI  - Lipoproteins and lipid peroxidation abnormalities in patients with chronic renal
      disease.
AB  - Increasing experimental and clinical evidence suggests that lipoproteins and
      lipid peroxidation can be important modulators in progressive kidney disease. A
      group of 54 patients with varying degrees of kidney impairment was studied to
      find the abnormalities in lipoproteins and lipid peroxidation. Lipoproteins and
      lipid peroxidation products, malondialdehyde (MDA) were measured in the plasma of
      54 chronic renal disease patients CGN 33, nephrosclerosis 11, 7CTIN, 1PCKD,
      unknown 2 and compared with values obtained from 32 healthy controls. The
      patients were divided into 5 groups according to serum creatinine levels: Group 1
      (serum creatinine of 2 mg/dl), group 2 (S. creatinine > 2-4 mg/dl), group 3 (S.
      creatinine > 4-8 mg/ dl), group 4 (S. creatinine > 8-12 mg/dl), group 5 (S.
      creatinine > 12 mg/dl). Plasma cholesterol was higher significantly than controls
      in patients with group 1, 2 and 3 (p < 0.01, < 0.001, < 0.05) respectively while
      plasma LDL-chol was statistically significantly different from controls only in
      group 2 patients (p < 0.001). Plasma VLDL-chol, beta-VLDL-chol, triglycerides,
      ratio of chol/HDL and LDL/ HDL showed high levels in all groups compared with
      controls but more evident in patients of group 2. Plasma HDL-chol decreased
      during the progression of renal failure. All groups had significantly elevated
      plasma malonyldialdehyde (MDA) vs controls (p < 0.001), especially highest value
      was found in group 2. Triglycerides, beta-VLDL chol, VLDL-chol LDL/HDL, chol/HDL
      correlated very closely with plasma MDA levels and also with serum creatinine.
      Patients with chronic renal disease showed lipoprotein abnormalities and
      accelerated lipid peroxidation. The evidence was more marked in patients with
      normal to mild renal insufficiency which suggested the role of oxidative stress
      early in the course of nephron injury.

PMID- 8855634
TI  - Cesarean hysterectomy in Siriraj Hospital: a 5-year review.
AB  - Cesarean hysterectomy remains a necessary procedure for life saving during
      abdominal delivery. The procedure itself is usually associated with considerable
      perioperative morbidity, especially when performed under emergency conditions.
      Obstetricians should identify patients at risk and anticipate the procedure and
      its complications. Knowledge of this operation and skill at its performance can
      be very helpful in reducing perioperative maternal and perinatal morbidity.

PMID- 8855635
TI  - Indoor radon in Thailand: a study with particular reference to its sources.
AB  - Measurements of radon gas were carried out on each floor of the four tall
      concrete buildings. The results show clearly that levels of radon concentration
      on the higher floors of the buildings were mostly comparable and occasionally
      were much higher than the ground-floor in contact with the earth. Hence, the
      findings indicate that the source of indoor radon is not only the surrounding
      soil but also other sources in the buildings, i.e. most likely radium-containing
      building materials.

PMID- 8855636
TI  - Evaluation of training medical students in patient-interviewing skills by three
      modes of learning.
AB  - Teaching interpersonal and communication skills to practice history taking is a
      part of a course on Foundation to Clinical Approach provided for third year
      medical students. They were trained in three modes: performing with SP, with
      peers and with groups. This study was conducted to assess the effect of training
      by three methods. Analysis of the assessment forms by tutors and students
      indicated that all behaviour and all methods were significantly different at
      0.001 and 0.003 and the highest score was found performing with SP. The
      behaviours which they performed were different among sections and the best
      performance was patient interview related to history taking and chief complaints.
      The students should improve their skills in beginning and ending the interview,
      asking open questions, clarifying the patient's understanding, increasing
      awareness of perceptions on patients especially the psychosocial aspects and
      feelings of patients. From the questionnaire, the tutors and students thought
      that this program was useful and every student should have a chance to practice
      with the extended time for a second performance after feedback or more than one
      rehearsal.

PMID- 8855637
TI  - P450scc deficiency (congenital lipoid adrenal hyperplasia): first reported case
      in Thailand and literature review.
AB  - A male infant presented with hyponatremia, hyperkalemia, generalized skin
      hyperpigmentation, and female type external genitalia. These clinical findings
      were compatible with mineralocorticoid, glucocorticoid and androgen
      insufficiency. Serum cortisol, progesterone and testosterone levels were
      extremely low after ACTH stimulation test, suggestive of defect in all of the
      adrenal steroidogenesis. Computed tomography demonstrated enlarged adrenal
      glands. The diagnosis of P450scc deficiency or lipoid congenital adrenal
      hyperplasia was based on all these characteristics. Physiologic replacement
      therapy with hydrocortisone and 9 alpha-fluorocortisol were effective and the
      patient achieved normal growth. The clinical characteristics, differential
      diagnoses, and prenatal diagnosis are discussed and reviewed.

PMID- 8855638
TI  - Successful implantation of transvenous automatic implantable cardioverter
      defibrillator (AICD): the first case report in Thailand.
AB  - We successfully implanted transvenously the AICD in a case of sudden cardiac
      arrest survivor. Though the device is very expensive, it is useful in some
      selected cases. With its diagnostic capabilities, the device may be useful in
      elucidating the underlying mechanism of Lai Tai.

PMID- 8855639
TI  - Sjogren-Larsson syndrome.
AB  - A 9-year-old boy with classical features of Sjogren-Larsson syndrome was
      reported. He had had diffuse dry skin with ichthyotic scales since birth. The
      skin biopsy was compatible with ichthyosis. At the age of two he was unable to
      walk normally and also had learning problems. Neurological examination revealed
      spastic paraparesis, macular degeneration and mild mental retardation. MRI of the
      brain and spinal cord revealed subcortical white matter and corpus callosal
      lesions as well as focal cerebral atrophy and diffuse spinal cord atrophy.

PMID- 8855641
TI  - Hospice care in Mississippi.

PMID- 8855640
TI  - When your patient asks: "Doctor, I'd like to get the blood test for the breast
      and ovary cancer gene".

PMID- 8855642
TI  - Case records of the Department of Medicine University of Mississippi Medical
      Center. Idiopathic sclerosing mediastinitis.

PMID- 8855643
TI  - The changing role of Medicare carriers.

PMID- 8855644
TI  - Hyperpigmentation associated with selenium sulfide lotion.

PMID- 8855645
TI  - Proper management of HIV/AIDS disease.

PMID- 8855646
TI  - Recruitment strategies for black women at risk for noninsulin-dependent diabetes
      mellitus into exercise protocols: a qualitative assessment.
AB  - The literature is devoid of any specific data describing exercise therapy in
      blacks at risk for diabetes. The increasing and striking prevalence of obesity
      and diabetes among several indigenous populations demonstrates the unfortunate
      interplay between genetic predisposition and a "modern" sedentary lifestyle. Any
      successful intervention to reduce the risk of acquiring or attenuating the
      severity of diabetes must focus on behavioral, cultural, psychosocial, and social
      factors that are amenable to change. Thus, the objective of this study is to
      present qualitative data that can be useful in the recruitment of blacks into
      exercise protocols that could prove to be beneficial in preventing diabetes.
      Focus groups were conducted on 57 black women residing in Washington, DC,
      Columbia, Maryland, and Hartford, Connecticut. Barriers to exercising included
      lack of child care, lack of transportation, neighborhood constraints, and family.
      Incentives that would increase black women's ability to participate in an
      exercise protocols include transportation, child care, and an exercise
      environment that includes blacks.

PMID- 8855647
TI  - Nontropical pyomyositis in patients with AIDS.
AB  - Nontropical pyomyositis in persons with acquired immunodeficiency syndrome (AIDS)
      is an unusual entity with only a few cases having been described in the United
      States. Staphylococcus aureus is the most common organism implicated. The
      infection usually presents in a subacute indolent fashion with minimal
      inflammation. Fever and leukocytosis may be absent, and blood cultures are
      frequently negative. The diagnosis usually can be established by a combination of
      clinical features, computed tomography or ultrasound, and prompt examination of
      material obtained by aspiration or debridement. This article describes two cases
      of S aureus pyomyositis in patients with AIDS and reviews the literature relevant
      to this infection.

PMID- 8855648
TI  - Geographic and temporal patterns of recurrent intentional injury in south-central
      Los Angeles.
AB  - To better understand geographic and temporal patterns of recurrent intentional
      injury, 285 consecutive trauma patients were evaluated prospectively. Fifteen
      were excluded because of immediate death or severe brain injury. The remaining
      270 patients were interviewed. Of these, 59 (22%) had been treated in a hospital
      for a total of 75 previous episodes of intentional trauma (mean: 1.3
      episodes/patient). In 66 of the 75 episodes, the patient recalled where treatment
      had been received (88%). Twenty-eight (42%) of the 66 episodes had been treated
      at King/Drew Medical Center (KDMC), 36 (55%) had been treated at a hospital
      within a 3-mile radius of KDMC, 48 (73%) within an 8-mile radius, and 63 (95%)
      within a 10-mile radius. Sixty-five percent of the episodes occurred 5 years or
      less prior to the current injury (range: 11 days to 30 years; mean: 4.9 years).
      Patients currently admitted for intentional injury were more likely to have had
      intentional injury previously than those with unintentional injury (27% versus
      12%). Based on these findings, we conclude that intentional trauma patients in
      our community remain in a defined geographic region and that there is a definable
      high-risk period for recurrent intentional injury. These conclusions should
      enhance the development of a framework on which future violence prevention
      programs can be designed.

PMID- 8855649
TI  - Colon trauma: primary repair evolving as the standard of care.
AB  - This study reviewed the management of colon injuries treated at the trauma
      surgical service, University of Nevada Medical Center between 1987 and 1992.
      Sixty-six patients sustained either blunt or penetrating colon injuries during
      the study period. The patients were divided into two groups: patients who
      underwent diverting colostomies and patients who underwent primary repair. Both
      groups were equally matched in terms of colon injury severity as well as trauma
      scores. The results indicated that primary colon repair was as safe if not safer
      than colostomy with less complications and at lower costs. The authors conclude
      that primary repair should be reevaluated in a critical manner as an evolving
      standard of care.

PMID- 8855650
TI  - Time management: a review for physicians.
AB  - This article reviews the basic concepts and techniques of time management as they
      relate to a medical lifestyle. Essential tools are described to help the
      physician reassess and sharpen skills for handling intensifying demands and
      constraints of juggling patient care, research, teaching, and family
      responsibilities. The historical background and principles of time management for
      three popular "best selling" techniques are critiqued. In addition, a fourth
      technique, or model, of time management is introduced for physician use.

PMID- 8855651
TI  - Radical prostatectomy: lower rates among African-American men.
AB  - This study compares radical prostatectomy rates by race among male Medicare
      patients in New York. A retrospective analysis was conducted of all radical
      prostatectomies performed on hospitalized male Medicare beneficiaries for the
      period 1991 through 1993. Basic trend data also were analyzed for 1990. Pattern
      analysis was conducted on the 4154 procedures performed between 1990 and 1993.
      The rate of radical prostatectomy rose dramatically during the 3-year period from
      1990 to 1992 among New York's 1.1 million male Medicare beneficiaries. The rates
      rose for both African Americans and whites. However, the annual rates of radical
      prostatectomy for African Americans were significantly below those for whites.
      Lower rates of radical prostatectomies were observed for African Americans in all
      age groups except the < 65-year-old group. However, the total number of radical
      prostatectomies in this age group were small in number. An important finding was
      the lower annual rates of radical prostatectomy for African Americans in the 65-
      to 69-year-old age group. During the period under study, prostate cancer among
      Medicare patients in New York rose by 33.8% for African Americans and 26.5% for
      whites. Significantly, local disease was found at the time of diagnosis in 70% of
      whites but in only 55% of African Americans. These data reflect later stage at
      diagnosis among African-American males. These results indicate that despite
      higher national rates for prostate cancer, male African-American Medicare
      patients in New York have reduced access to radical prostatectomy as a treatment
      modality. This is especially of importance in the < 70-year-old group in whom
      most authorities consider the procedure appropriate. The reasons for this reduced
      access are discussed as are the measures needed to remedy the underlying
      inequities in health care.

PMID- 8855652
TI  - David Jones Peck, MD: a dream denied.

PMID- 8855653
TI  - Long-term survival of an AIDS patient with a tuberculous cerebral abscess.
AB  - Unlike other forms of tuberculosis, tuberculous cerebral abscess is a rare
      complication of human immunodeficiency virus (HIV) infection and usually presents
      at a late stage of the disease. This article describes a case of tuberculous
      cerebral abscess in an HIV-infected patient that was effectively treated with
      surgery and chemotherapy. The patient has survived more than 5 1/2 years since
      being diagnosed and remains in good health.

PMID- 8855654
TI  - Was Urbilateria segmented?

PMID- 8855655
TI  - Myotonic dystrophy, knockouts, warts and all.

PMID- 8855656
TI  - Non-orthologous gene displacement.

PMID- 8855657
TI  - A simple and inexpensive method for RNA extraction from yeasts.

PMID- 8855658
TI  - An efficient method for the extraction of DNA from vertebrate tissues.

PMID- 8855659
TI  - A simple device to prevent contamination during spin-column gel filtration.

PMID- 8855660
TI  - A rapid and easy method for DNA recovery from agarose gels using Wizard
      minicolumns.

PMID- 8855661
TI  - A highly sensitive and non-lethal beta-galactosidase plate assay for yeast.

PMID- 8855662
TI  - DNA ligation quality control by competitive PCR.

PMID- 8855663
TI  - A quantitative model for the cdc2 control of S phase and mitosis in fission
      yeast.
AB  - In this article we consider the role of the cyclin-dependent protein kinase cdc2
      in regulating progression through the fission yeast cell cycle. The onset of
      mitosis is governed by cdc2 in partnership with the B-type cyclin, cdc13. Recent
      evidence shows that the cdc2-cdc13 complex can also control the onset of S phase
      and, in addition, ensures that there is only one S phase per cell cycle. This
      leads us to propose a novel quantitative model in which different levels of cdc2
      activity regulate cell-cycle progression: S phase is initiated when protein
      kinase activity increases from a very low to a moderate level; maintenance of
      this moderate level prevents re-initiation of S phase, and a further increase of
      activity to a high level initiates mitosis. Inactivation of the kinase activity
      at the end of mitosis resets the cell for a new cell cycle.

PMID- 8855664
TI  - Core promoters and transcriptional control.
AB  - Many biological processes are controlled, spatially and temporally, at the level
      of transcription. Thus, understanding the mechanisms of transcriptional
      regulation of gene expression is critical in deciphering the molecular modes of
      differentiation and development of a eukaryotic cell. Transcriptional control is
      mediated largely through interactions of regulatory transcription factors with
      their cognate enhancer elements. The regulatory signals generated at enhancer
      elements are communicated to the general transcription machinery formed at the
      core promoter elements of all genes. Recent observations suggest that the general
      transcription machinery can also generate regulatory signals independent of
      enhancer-generated interactions. Thus, the transcriptional regulation of gene
      expression, both in time and in space, may result from appropriate interfacing of
      independent signals generated at the core promoter and at the enhancer.

PMID- 8855665
TI  - Genetic analysis of aging in Saccharomyces cerevisiae.
AB  - The natural limits to life span are poorly understood. Yeast is a good model
      organism for studies of the aging process because single cells can be followed
      for many cell divisions and their loss of division potential follows kinetics
      identical to mortality rates in complex organisms. Recent experimental approaches
      in yeast are beginning to lead to basic models of the factors that facilitate
      aging.

PMID- 8855666
TI  - One hundred years of positional information.
AB  - One mechanism by which spatial patterns of cell differentiation could be
      specified during embryonic development and regeneration is based on positional
      information. Cells acquire a positional value with respect to boundaries and then
      interpret this in terms of a programme determined by their genetic constitution
      and developmental history. The signals and the molecular basis of such a system
      have both been rather well conserved. Recent work has shown that cells can
      respond to quite small differences in the concentrations of molecules whose
      concentration could provide positional information.

PMID- 8855667
TI  - The coevolution of gene family trees.
AB  - Gene duplication mutants arise spontaneously at a high rate in bacteria,
      bacteriophages, insects and mammalian cells, and are generally viable. Thus, the
      rate-limiting step in the evolutionary process of gene duplication and divergence
      was probably not gene duplication per se. Rather, it is likely that only a small
      fraction of all duplicated genes were retained, and were able to diverge into new
      specificities. Furthermore, gene duplications and functionally related gene
      families often show similarities in divergence dates, functional specificities,
      and phylogenetic tree topologies. These correlations suggest that the family
      trees of functionally related gene families co-evolved because functionally
      complementary gene duplication and divergence events tended to be retained by
      natural selection.

PMID- 8855668
TI  - The C. elegans expression pattern database: a beginning.

PMID- 8855669
TI  - Onchocerciasis. Progress towards elimination in the Americas.

PMID- 8855670
TI  - A study of the social and clinical characteristics of depressive illness among
      Ghanaian women--(1988-1992).
AB  - The social and clinical characteristics of one hundred and thirty-one women who
      attended the psychiatric outpatient clinic for the first time at the Department
      of Psychiatry, University of Ghana Medical School, within five years (1988-1992)
      were studied. The data suggested that the peak age of depressed women at
      consultation was between twenty and forty; and that a significant proportion of
      them were in the married group. Moreover the majority have no or very little
      education and thus little opportunity for gainful employment hence the majority
      were self employed. This finding is markedly different from the findings in the
      Western Countries, where the depressed women were much older, between thirty-five
      and fifty-four years; single and were gainfully employed. The average number of
      children per woman were between five and eight and the women had no adequate
      financial support from their husbands. These social characteristics reflected in
      the life-style and the kind of social stresses imposed upon these women in coping
      with life. These stresses showed in the clinical symptoms they represented, which
      were mainly somatisation disorder and somatic symptoms, with headaches and
      insomnia being the most prominent. However, psychological symptoms such as morbid
      thoughts were found to be few at this first consultation. It was highlighted that
      the social stresses might possibly be the causes of the clinical presentation of
      the depressed Ghanaian women. It was suggested that the specificity of headaches
      as a symptom of other psychiatric disorders other than depressive illness, for
      example schizophrenia and other endogenous psychiatric disorder among Ghanaian
      women require further research.

PMID- 8855671
TI  - Stab wounds in The Gambia.
AB  - Over a 24-month period (January 1990 to December 1991) 337 cases of stab wounds
      were managed at the Royal Victoria Hospital, Banjul, The Gambia. All stabbing
      occurred in and around Banjul and victims were predominantly male (99.1%).
      Stabbed subjects were mostly involved in fights (98.2%). The mean age of the
      subjects was 27.6 +/- 10.5 years. 155 subjects (46%) required emergency room
      treatment only while 182 (54%) needed hospitalisation. Superficial lacerations
      predominated (94.3%) while other major complications included
      haemothorax/pneumothorax (2.4%), haemopericardium/pneumopericadium (0.3%),
      cardiac lacerations (0.6%), and haemoperitoneum (2.4%). Visceral injuries managed
      were: Heart lacerations (2%), Liver lacerations (1.2%), lung lacerations (2.4%),
      peritoneal lacerations (0.6%), gut perforation (0.6%) and pericardial
      complications of inadequate initial management. Anaesthetic techniques used for
      major procedures including Thoracotomies and Laparotomies were simple to ensure
      safety and assure quick post anaesthetic recovery. All patients had an uneventful
      recovery. In a situation of restricted medical facilities, we have recorded
      successful management outcomes without resorting to mandatory exploratory
      celiotomy and expensive diagnostic procedures.

PMID- 8855672
TI  - Lymphadenopathy in Nigerian children.
AB  - The histopathologic findings on 121 excised enlarged lymph nodes from 48 female
      and 73 male Nigerian children resident in Ife-Ijesa zone of Western Nigeria over
      a period of ten years (1982-1991) form the basis of this study. Patients' ages
      ranged from 2 months to 15 years. Most of the patients (81%) were aged 6 years
      and above. The cervical region was the commonest site of lymphadenopathy (48%)
      and localized lymphadenopathy was the rule. Chronic specific inflammation
      (tuberculosis, toxoplasmosis, and histoplasmosis) predominated as a cause of
      lymphadenopathy (44%) compared with non specific lymphadenitis (31%) and
      malignant tumours (24%). Tuberculosis was the commonest cause of chronic specific
      lymphadenitis and was commoner in girls. The cervical region was the commonest
      site for chronic specific lymphadenitis, as well as Hodgkin's and non-Hodgkin's
      lymphoma. The lymphomas were more common in males. The peak incidence for
      Hodgkin's disease was between the ages of 12 and 15 years.

PMID- 8855673
TI  - Incidence of pyrexia in patients undergoing haemodialysis.
AB  - Four patients on maintenance haemodialysis at the Lagos University Teaching
      developed pyrogenic reactions during treatment. Blood cultures were negative but
      the haemodialysates were grossly contaminated, mostly with Gram-negative bacilli,
      implicating their endotoxin as the cause of the observed pyrogenicity. The water
      reservoirs supplying the dialysis centre were grossly contaminated (counts 2.0 x
      10(2) cfuml-1) with Gram-negative bacteria such as Pseudomonas aeruginosa, Ps.
      fluorescens, Alcaligenes faecalis, Achromobacter spp. and a Gram-positive
      organism, Micrococcus spp. These were the organisms isolated from the
      haemodialysates. At each sampling time, though fewer bacterial species were
      isolated from the haemodialysates, contrast the water reservoirs, the population
      of each bacterial type recovered from both samples was higher in the
      haemodialysates indicating a build up of the organisms within the haemodialysis
      machines. These findings therefore call for regular monitoring of the level of
      contamination of water use for mixing haemodialysis fluid in order to know when
      critical level is being exceeded.

PMID- 8855674
TI  - Genital herpes simplex virus infection in females in Ibadan Nigeria.
AB  - In a study of female patients attending the Sexually Transmitted Diseases Clinic
      of the University College Hospital Ibadan, Nigeria, Herpes simplex virus was
      isolated from the cervix of 5 of 117 patients, a prevalence rate of 4.3%. Two
      (1.7%) of these patients had HSV in the vagina. The viruses were identified by
      culture in HEp-2 cell line, chloroform sensitivity test, complement fixation test
      and indirect immuno-fluorescent antibody technique. Only one (20%) of the five
      patients has HSV-1 in the endocervix.

PMID- 8855675
TI  - An open evaluation of the efficacy and safety of the new macrolide roxithromycin
      in the treatment of lower respiratory tract infections and pneumonia in Nigerian
      patients.
AB  - Roxithromycin, a new introduction into the macrolide class of antibiotics
      possesses favourable pharmacokinetic properties enabling a once daily dosing.
      This study evaluates its efficacy, safety and tolerability, previously
      demonstrated in Europe and North America, in Nigeria patients suffering from
      lower respiratory tract infections. 32 patients, aged 18-65 years with acute
      bronchitis/acute exacerbation of chronic bronchitis and pneumonia were
      administered roxithromycin 300 mg once daily. 25 patients (12 males, 13 females:
      aged 39.2 +/- 2.7 years) were evaluable for clinical efficacy at the end of the
      study. The mean duration of treatment was 6.9 +/- 0.5 days. 22 patients (88.0%)
      responded to therapy. Sputum culture was positive in 5 patients (20.0%):
      Streptococcus pneumonia and resistant Klebsiella pneumonia. Therapy was
      discontinued in 3 patients due to non-response. The two patients in whom
      Klebsiella were isolated did not show any significant clinical improvement. The
      third non responding patient developed empyema. Gram negative bacilli were
      identified in the pleural aspirate but no patients with resistant Streptococcus
      pneumonia improved clinically. Adverse effects were mild, transient and included
      nausea (4) and diarrhoea (1). The study suggests that roxithromycin is an
      effective and well tolerated antibacterial in the treatment of lower respiratory
      tract infection.

PMID- 8855676
TI  - Are closed dressing of burns in children effective?
AB  - Burns are a common home accident world-wide. Sixty-six patients in the Paediatric
      Department were treated by closed dressing and were followed up for a period of
      two months. The peak age was between 2-5 years with the causative agent being hot
      water. The majority of burns were mild to moderate in severity, that is, first
      and second degree burns. In the majority of cases, a definite dressing was
      applied within 24 hours of the burn. 60% of patients were discharged home within
      15 days of admission. Three patients died from sepsis (one patient) and probable
      electrolyte imbalances (2 patients). Other complications were few. The result
      show that closed dressing of burns in our experience definitely has advantages
      over the traditional open methods and is to be preferred.

PMID- 8855677
TI  - Cervical ectopic pregnancy: a case report.
AB  - A 24 year old Nigerian woman with cervical pregnancy, a very rare type of ectopic
      pregnancy, is presented. The disorder can be life-threatening and usually there
      is difficulty in differentiating it from the cervical phase of an incomplete
      abortion as well as bleeding cervical fibroid. Ultrasound scan has been found
      helpful in the diagnosis of cervical ectopic pregnancy. The conservative
      management and the possible alternative surgical management, based on the
      clinical presentation, are discussed.

PMID- 8855678
TI  - Gastric volvulus: a report of four cases.
AB  - In this communication we report 4 cases of gastric volvulus seen at the
      Department of Surgery University College Hospital, Ibadan, over a four-year
      period giving a hospital incidence of one case per year. The often difficult
      diagnosis and mode of management is presented along with a review of world
      literature. One of our cases is the fifth case of combined organomesenteroaxial
      volvulus in a child reported in world literature.

PMID- 8855679
TI  - A cluster of Escherichia coli O157:H7 infections with the hemolytic-uremic
      syndrome and death in California. A mandate for improved surveillance.
AB  - In mid-January 1993, an outbreak of Escherichia coli O157:H7 infections
      associated with eating hamburger patties at a fast-food restaurant chain (chain
      A) was reported in Washington State. From mid-December to mid-January, 9 cases of
      E coli O157:H7-associated bloody diarrhea and the hemolytic-uremic syndrome had
      been reported in San Diego County, California. A total of 34 persons had bloody
      diarrhea, the hemolytic-uremic syndrome, or E coli O157:H7 organisms isolated
      from stool during the period November 15, 1992, through January 31, 1993.
      Organisms of E coli O157:H7 identified from 6 persons were indistinguishable from
      those of the Washington outbreak strain. Illness was associated with eating at
      chain A restaurants in San Diego (odds ratio, 13; 95% confidence interval, 1.7,
      99) and with eating regular-sized hamburgers (odds ratio, undefined; lower-limit
      95% confidence interval, 1.3). Improved surveillance by mandating laboratory- and
      physician-based reporting of cases of E coli O157:H7 infection and the hemolytic
      uremic syndrome might have alerted health officials to this outbreak sooner,
      which could have resulted in earlier investigation and the institution of
      measures to prevent more cases.

PMID- 8855680
TI  - Pediatric hospital admissions for measles. Lessons from the 1990 epidemic.
AB  - To examine the descriptive epidemiology of serious measles complications and
      associated hospital costs during a major epidemic, we used California population
      based hospital discharge data to identify hospital admissions for measles during
      1986 through 1990 (ICD-9 code 055, n = 4,201). We examined 5-year trends and, for
      1990 pediatric epidemic cases (n = 2,234), sociodemographic and hospital
      admission financial data. Hospital admission rates for measles rose significantly
      between 1986 and 1990. During the 1990 epidemic, preschool children aged 1 to 5
      years, Medi-Cal (California's Medicaid) beneficiaries, Hispanics, and those
      living in urban counties accounted for most hospital admissions. Young infants
      and residents of southern California and the San Joaquin Valley had the highest
      risks. Medi-Cal beneficiaries and Asian children were at an increased risk for
      death during the hospital stay. The average hospital admission cost was $8,201,
      and the average length of hospital stay was 4.6 days. Hospital costs amounted to
      $18 million, two thirds of which was paid for by Medi-Cal. Measles is a serious
      disease that can result in severe complications requiring lengthy and costly
      hospital stays. We must remain alert to its continuing threat, complications, and
      resulting financial burdens.

PMID- 8855681
TI  - Patient preferences for management of localized prostate cancer.
AB  - We designed this study to determine whether patients with early localized
      prostate cancer prefer surgical intervention over watchful waiting, which aspects
      of the 2 management strategies influence patient preferences, and whether there
      are patient characteristics that predict their preferences for 1 strategy over
      the other. Structured interviews were used with 140 male patients seen
      consecutively at a university-based Department of Veterans Affairs Medical Center
      outpatient clinic. The mean age of the patients was 66.3 years. Of the 140
      patients, 53% preferred surgical treatment, 42% preferred observation, 4%
      preferred that their physician make the decision, and 1% preferred radiotherapy.
      Of 74 patients selecting surgical intervention, 92% (68) reported that the
      possibility of complete tumor removal was the strongest factor influencing their
      decision. Of those selecting observation, 80% (47/59) reported being most
      influenced by the complications of an operation. Older patients were
      significantly (P < .002) more likely to prefer expectant management. We conclude
      that tumor excision is an important factor influencing patient preferences for
      treatment, irrespective of survival benefits. This factor should be considered
      when designing approaches to providing information to patients about alternative
      treatments.

PMID- 8855682
TI  - Substance-impaired physicians probationary and voluntary treatment programs
      compared.
AB  - We compared the characteristics and treatment outcomes of substance-impaired
      physicians monitored by two different programs in Oregon: a probationary program
      administered by the Oregon Board of Medical Examiners and the confidential,
      voluntary Diversion Program for Health Professionals. Demographic, substance use,
      and treatment outcome variables were obtained by a retrospective medical record
      review from 41 physicians monitored by the Oregon board and 56 physicians
      monitored by the diversion program during a 3-year study period. Compared with
      physicians monitored by the Oregon board, physicians in the diversion program
      were younger, more likely to be in training programs and less likely to be in
      hospital-based practice settings, more often reported by immediate rather than
      third-party contacts, more likely to choose in-state inpatient treatment than out
      of-state treatment, and less likely to have concurrent mental illness diagnoses
      (P < .05 for all comparisons). Short-term relapse rates did not differ
      statistically between the groups (22.0% for the Oregon board group, 14.3% for the
      diversion program group). The higher number of younger physicians and physicians
      in training and tendency toward increased reporting by immediate contacts in the
      diversion program suggested earlier intervention than in the Oregon board group.

PMID- 8855683
TI  - Western impressions of the Hong Kong health care system.
AB  - Hong Kong, Taiwan, Singapore, and Malaysia are initiating health care reform to
      meet the changing demands of populations with improved socioeconomic status and
      access to modern technologies and who are living longer than in previous
      generations. Hong Kong, in particular, is facing a unique set of circumstances as
      its people prepare for the transition in 1997 from a British colony to a Special
      Administrative Region of China. While spending only 4% of its gross domestic
      product on health care, it has a large and regulated public hospital system for
      most inpatient medical care and a separate, loosely regulated private health care
      system for most outpatient medical care. In 1993 the Secretary for Health and
      Welfare of Hong Kong initiated a year-long process to debate the pros and cons of
      5 fundamental programs for health care reform. After a year of open consultation,
      options were chosen. We describe the Hong Kong health care system, the
      fundamental changes that have been adopted, and lessons for reformers in the
      United States.

PMID- 8855685
TI  - Percutaneous core biopsy of the breast.

PMID- 8855686
TI  - Current status of thrombolysis.

PMID- 8855687
TI  - Magnetic resonance imaging, positron emission tomography, and single-photon
      emission computed tomography in epilepsy.

PMID- 8855684
TI  - Cervical spondylosis. An update.
AB  - Cervical spondylosis is caused by degenerative disc disease and usually produces
      intermittent neck pain in middle-aged and elderly patients. This pain usually
      responds to activity modification, neck immobilization, isometric exercises, and
      medication. Neurologic symptoms occur infrequently, usually in patients with
      congenital spinal stenosis. For these patients, magnetic resonance imaging is the
      preferred initial diagnostic study. Because involvement of neurologic structures
      on imaging studies may be asymptomatic, consultation with a neurologist is
      advised to rule out other neurologic diseases. In most cases of spondylotic
      radiculopathy, the results of conservative treatment are so favorable that
      surgical intervention is not considered unless pain persists or unless there is
      progressive neurologic deficit. If indicated, a surgical procedure may be done
      through the anterior or posterior cervical spine; results are gratifying, with
      long-term improvement in 70% to 80% of patients. Cervical spondylotic myelopathy
      is the most serious and disabling condition of this disease. Because many
      patients have nonprogressive minor impairment, neck immobilization is a
      reasonable treatment in patients presenting with minor neurologic findings or in
      whom an operation is contraindicated. This simple remedy will result in
      improvement in 30% to 50% of patients. Surgical intervention is indicated for
      patients presenting with severe or progressive neurologic deficits. Anterior
      cervical approaches are generally preferred, although there are still indications
      for laminectomy. Surgical results are modest, with good initial results expected
      in about 70% of patients. Functional outcome noticeably declines with long-term
      follow-up, which raises the question of whether, and how much, surgical treatment
      affects the natural course of the disease. Prospective randomized studies are
      needed to answer these questions.

PMID- 8855688
TI  - Imaging of appendicitis.

PMID- 8855689
TI  - Spiral and ultrafast computed tomography for noninvasive cardiac imaging in
      children.

PMID- 8855690
TI  - Doppler ultrasonography of transjugular intrahepatic portosystemic shunts.

PMID- 8855691
TI  - Spiral computed tomography and magnetic resonance imaging in the detection of
      pulmonary emboli.

PMID- 8855692
TI  - Magnetic resonance imaging of radiographically occult bony trauma.

PMID- 8855693
TI  - Magnetic resonance imaging of the breast.

PMID- 8855694
TI  - Radiosurgery.

PMID- 8855695
TI  - Tension pneumoperitoneum.

PMID- 8855696
TI  - Wegener's granulomatosis presenting as dilated cardiomyopathy.

PMID- 8855697
TI  - Prophylaxis against opportunistic infections in patients infected with the human
      immunodeficiency virus.

PMID- 8855698
TI  - Caution: the meter is running informing patients about health care costs.

PMID- 8855699
TI  - California's 1988-1991 measles epidemic--the last one?

PMID- 8855700
TI  - Progress in treatments for substance-impaired physicians.

PMID- 8855701
TI  - Genetics and homosexuality.

PMID- 8855702
TI  - Alcohol and the workplace.

PMID- 8855703
TI  - Alcohol and the media.

PMID- 8855705
TI  - Wisconsin must act on compulsive gambling.

PMID- 8855704
TI  - Alcohol and primary health care.

PMID- 8855706
TI  - Problem gambling hits home.

PMID- 8855707
TI  - Winning isn't easy...

PMID- 8855708
TI  - Gambling away the golden years.

PMID- 8855709
TI  - Physician's health: getting the help you may need.

PMID- 8855710
TI  - Medical approaches to gambling issues--I: The medical condition.
AB  - Gambling is a common human behavior. People who gamble encounter physicians. At
      times, gambling can produce adverse consequences for the player. Persistence of
      gambling despite adverse consequences can be called problem gambling. Roughly 1%
      of adults and 3% of adolescents exhibit signs of a medical disorder defined as
      pathological gambling. In many areas, including Wisconsin, gambling is increasing
      in legality, availability, and prevalence, and with it, pathological gambling is
      increasing in prevalence. This paper provides a descriptive review of gambling
      behaviors and the condition of pathological gambling, in the hope of increasing
      the awareness of practicing physicians, medical educators and researchers, and
      public policy makers, about what is known about these behaviors and the features
      of gambling illness that may present in a clinical setting. A companion paper
      focuses on the opportunities for constructive clinical activity by physicians
      regarding gambling problems.

PMID- 8855711
TI  - Medical approaches to gambling issues--II: The medical response.
AB  - Gambling behaviors cover a spectrum from an enjoyable benign form of social
      entertainment to a disabling and potentially lethal medical condition. A
      companion paper, Medical Approaches to Gambling Issues--I: The Medical Condition,
      provides a literature review of gambling in its pathological and nonpathological
      forms. Physicians encounter patients who gamble, patients who have a treatable
      disorder of pathological gambling and family members of problem and pathological
      gamblers. This paper is intended to aid practicing physicians in their care of
      their patients who gamble and experience problems related to gambling, as well as
      in the care of those among their patient caseload who are symptomatically
      affected by someone else's gambling.

PMID- 8855712
TI  - The burden of diabetes in Wisconsin: diabetes-related amputations, 1994.

PMID- 8855713
TI  - What's new in ... clinical pharmacology and therapeutics.

PMID- 8855714
TI  - What's new in ... obstetrics and gynecology.

PMID- 8855715
TI  - [Developments of highly stereoselective domino reactions and application to
      medicinal chemistry].
AB  - Simple and highly effective methods for the synthesis of polycyclic ring systems
      via two types of intramolecular domino reactions are developed and presented. The
      first example is an intramolecular double Michael reaction, whose scope
      limitation, mechanism and application to natural product synthesis are discussed.
      The intramolecular Michael-aldol reaction is the second case, which provides a
      nice method for the preparation of polycyclic compounds having a four-membered
      ring system. In addition, some related reactions of these methods are described.

PMID- 8855716
TI  - [Mechanisms of cytotoxic drug-induced emesis and its prevention].
AB  - In this review, I have attempted to provide an overview of the pathways by which
      cytotoxic drugs induce emesis. The mechanisms of serotonin 5-HT3 antagonists and
      new antiemetics are also discussed. Old data especially from the experiments
      employing area postrema ablation must be re-evaluated because it is likely that
      the operation has damaged other important nucleus in the brain stem. Therefore,
      the concept of the chemoreceptor trigger zone and "vomiting center" proposed by
      Borison et al. in 1950s is questionable. Nausea and vomiting caused by cytotoxic
      drugs have been a serious problem in anti-cancer therapy and prompted lots of
      scientists to find the mechanism and to develop antiemetics. Effectiveness of 5
      HT3 antagonists were shown in late 1980s, and now they are clinically available.
      I have investigated their mechanisms using Suncus murinus and proposed that the
      pathways by which cisplatin, one of most emetogenic drugs, induces emesis are as
      follows: 1) cisplatin is converted to an active metabolite(s), 2) the
      metabolite(s) somehow produces oxygen free radicals in the enterochromaffin
      cells, 3) the free radicals release serotonin, 4) the released serotonin
      stimulates 5-HT3 receptors located on the vagus afferents, 5) impulses are
      transmitted to the brain stem, or emetic pattern generator and initiate emetic
      reflex. Therefore, scavengers of free radicals and antioxidants can be a new type
      of antiemetic drug.

PMID- 8855717
TI  - [Biological properties of the colony-promoting activity in extracts prepared from
      murine kidney].
AB  - Aqueous extracts prepared from the murine kidney (MKE) promoted colony formation
      derived from murine hematopoietic progenitor cells in serum-free cultures
      stimulated by interleukin-3 (IL-3) and erythropoietin (Epo). MKE itself did not
      stimulate any colony formation. MKE preferentially enhanced granulocyte
      macrophage colony forming units (CFU-GM), but did not promote any erythroid
      colony formation. The CFU-GM colony promotion by MKE was observed at day 6 after
      the culture started, and the colony-promoting activity (CPA) was maintained at
      the same level until day 16. MKE showed no CPA in the cultures using cells
      obtained from 5-FU-injected mice and from c-kit(+)-enriched treatment.
      Furthermore, MKE acted synergistically with granulocyte-colony-stimulating factor
      (CSF), macrophage-CSF, IL-6 and IL-11 on colony formation, but did not act with
      GM-CSF, stem cell factor and Epo. From the results of various experiments and gel
      filtration chromatography, it is estimated that the colony-promoting factor
      detected in MKE is a heat stable protein with about 20 KDa molecular weight.
      These results suggest that MKE promotes colony formation by murine myeloid
      progenitor cells, and that the target cell populations of MKE are relatively
      mature in the hematopoietic differentiation pathway.

PMID- 8855718
TI  - [Study of components in crude drugs by headspace gas chromatography. II.
      Components of atractylodes].
AB  - Determination of volatile components in essential oils from Atractylodis plants
      was studied by headspace gas chromatography. The crude drug of 0.20 g with 1.0 ml
      of water in a capped vial was heated at 130 degrees C for 45 min. Then 0.5 ml of
      vaporized components were collected by gas tightsillinge, and were applied into
      the injection port of GC or GC/MS. Consequently we could analyze and confirm the
      following components; hinesol and beta-eudesmol were found to be contained in
      Atractylodis Lanceae Rhizoma and atractylon in Atractylodis Rhizoma. beta
      Eudesmol was analyzed by headspace gas chromatography, and the obtained
      calibration curve showed good linearity over the range from 2.5 micrograms to
      10.0 mg. The result agreed with those obtained using numerical analyses by the
      steam distillation method. Atractylodis was found to have a wide variety of
      components depending on the available sources and on the stored conditions. This
      method was, therefore, more rapid and simpler determination of essential oils in
      crude drugs using headspace gas chromatography than those used previously. The
      method was useful means of the analyses of components in crude drugs such as
      Atractylodis plants and quality control.

PMID- 8855719
TI  - [Studies on the synthesis of cholecystokinin A receptor antagonists. IV.
      Synthesis and cholecystokinin A receptor inhibitory activities of benzimidazole
      derivatives].
AB  - A number of benzimidazole derivatives were synthesized and tested for
      cholecystokinin A (CCK-A) receptor inhibitory activity in order to study
      structure-activity relationships. Significant CCK-A receptor inhibitory
      activities were found in the compounds having carboxyl or tetrazolyl group. As
      the most preferred compound, 4-(5,6-dichlorobenzimidazol-2-yl)-N-(3
      methoxypropyl)-N-pentylg lutaramic acid (4g) was selected.

PMID- 8855720
TI  - [Reaction of 3-hydroxy-dihydrosantonin with TsOH. A formal synthesis of
      dihydrocotunolide].
AB  - In connection with our another project a relatively large quantity of 5 was
      required. We, therefore, investigated the reaction of 3 with TsOH; this gave a
      diene mixture 7a, 7b, 6 and 5 in a ratio of 8:2:4:1. Almost the same 8:2:1
      "equilibrium mixture" of the dienes 7a, 7b and 5 was also obtained when the
      purified samples of 5 and 7a were independently treated with TsOH under the same
      conditions. The above results suggest that the dienes might be produced in the
      following way; beta-elimination of H2O from 3 gives a homoannular diene 5. The
      protonation to the more electron-rich tetrasubstituted C4-C5 double bond of 5
      from the less hindered alpha-side followed by the isomerization of the double
      bond gives 7a. 7b is formed via 7a and/or 5 by the double bond isomerizations. On
      the other hand, 6 is formed by concerted elimination of H2O between C3-OH and C6
      H. As a result of these studies, the synthetic precursor of dihydrocostunolide 7b
      which was already prepared by Corey in 6 steps (ca. 7%) from santonin was
      synthesized in 3 steps (ca. 6%) from the latter.

PMID- 8855721
TI  - Hepatitis C: sexually exposed?

PMID- 8855722
TI  - Gastroenterology and hepatology fellowships: are we meeting the needs of our
      trainees?

PMID- 8855723
TI  - Therapy in chronic hepatitis C: say goodbye to the 6-month interferon regimen.

PMID- 8855724
TI  - Critical appraisal of enteral nutrition as primary therapy in adults with Crohn's
      disease.

PMID- 8855725
TI  - Nonsteroidal anti-inflammatory drugs, Helicobacter pylori, and ulcers: where we
      stand.
AB  - BACKGROUND: Despite the progress in the diagnosis and treatment of Helicobacter
      pylori-related peptic ulcer disease, it has become apparent that we may be in the
      midst of an epidemic of nonsteroidal anti-inflammatory drug ulcers and ulcer
      complications. We also have almost no information about whether there is a link
      between ulcers in NSAID users and H. pylori infection or whether clinically
      significant interactions occur. METHODS: Current data regarding the diagnosis,
      prevention, and treatment of NSAID-induced ulcers and the possible relationship
      between H. pylori ulcers and NSAID use is reviewed. CONCLUSION: We need to
      rethink past conclusions about NSAIDs and gastroduodenal complications and also
      re-do many of the experiments, taking into account the H. pylori status of the
      patient (infected, uninfected, cured). It is predicted that the epidemic of NSAID
      complications will only get worse. Only the future will tell whether selective
      COX II inhibitors or NO-NSAIDs that incorporate a nitroxybutyl moiety will
      actually provide the same benefit at lower risk. Until then we must rely on more
      rational use of NSAIDs, and misoprostol to keep the number of complications at a
      minimum.

PMID- 8855726
TI  - Transmission of hepatitis C virus between spouses: the important role of exposure
      duration.
AB  - OBJECTIVES: Although interspousal transmission of hepatitis C virus (HCV) has
      been studied, the factors responsible for it remain unclear. METHODS: To
      investigate the transmission of HCV between spouses and the related risk factors,
      100 anti-HCV-positive index patients and their spouses were studied. RESULTS:
      Overall, anti-HCV was detected in 17 (17%) spouses, 15 of whom were also positive
      for HCV RNA, and 11 couples were infected with the same genotype. The anti-HCV
      positive rate was higher in spouses married longer than 20 yr compared with those
      married less than 20 yr (22 vs 6%, p < 0.05), and the infection was correlated
      with the duration of their actual exposure to the index patients but not with
      serum HCV titers. The infected couples had more frequent sexual contacts and more
      commonly shared tooth-brushes than those with uninfected spouses. CONCLUSION:
      Spouses of patients with chronic hepatitis C have a higher risk of acquiring HCV
      that increases with longer marriage and duration of exposure, and they should be
      educated about how to avoid contracting HCV infection from their spouses.

PMID- 8855727
TI  - Attitudes and expectations of 1995 gastroenterology graduates about
      gastroenterology.
AB  - OBJECTIVE: To learn more about current attitudes and expectations of recent (June
      1995) graduates of gastroenterology fellowship programs, why they chose either a
      private practice or academic career, and what impact managed care or health care
      reform had in their decision. METHODS: Between April and June 1995, and 8-page,
      35-question survey questionnaire was mailed to graduating fellows and returned
      for evaluation. RESULTS: Graduates believed managed care had an impact on job
      availability, but it was not a factor in their job choice. Forty percent of the
      respondents reported that finding a job was either difficult or very difficult.
      The majority of respondents (67%) are pursuing a career in private practice. Most
      private practice physicians (PP) trained in 2-yr programs whereas academic
      physicians (AC) trained for the most part in 3-yr programs. The principal
      criteria on which decisions regarding job selection were based were similar
      between the two groups: co-workers, geographic location, access to patient care,
      and ability to perform endoscopy. Respondents in PP and AC expected to work 50-70
      h/wk, care for patients with similar diseases, and have ample time for family.
      They would choose GI again as a career and believed that there is a future in GI.
      Salary expectations varied markedly between the two groups, and AC physicians
      were more concerned about their future financial needs. Twenty percent of PP
      physicians and 71% of AC physicians plan to participate in clinical research.
      CONCLUSIONS: Recent graduates of gastroenterology fellowship programs continue to
      have high expectations of their future careers. Although some had difficulty
      finding a job and stated that, although managed care had an impact on the job
      market, it had not yet become a major factor in their job selection.

PMID- 8855728
TI  - Incidence of adenomas after curative resection for colorectal cancer.
AB  - OBJECTIVE: The benefits of periodic colonoscopic surveillance after curative
      resection for colon cancer are controversial. We investigated the incidence,
      size, and time interval to the detection of recurrent adenomatous polyps in
      patients who have undergone resection of a colorectal cancer. METHODS: In this
      retrospective study, the records of 351 patients who underwent curative resection
      for colorectal carcinoma between 1967 and 1991 were reviewed. Sixty-one patients
      were excluded because of incomplete data. RESULTS: Eighty-seven patients (30%)
      were found to have had at least one adenoma. Twelve patients had more than five
      adenomas. The median time to diagnosis was 24 months. Forty-six patients of the
      87 (52.9%) had polyp recurrences within 2 yr after cancer resection. CONCLUSION:
      This group of patients is at increased risk for the development of adenomatous
      polyps. Surveillance colonoscopy and polypectomy may reduce the incidence of
      metachronous colon cancer.

PMID- 8855729
TI  - Role of small bowel biopsy in the endoscopic evaluation of adults with iron
      deficiency anemia.
AB  - OBJECTIVES: The recommended evaluation of adult patients presenting with iron
      deficiency anemia (IDA) includes the performance of colonoscopy and
      esophagogastroduodenoscopy. IDA is a common feature in patients with celiac
      disease and, in several, may be the only presenting sign. The performance of
      small bowel biopsy (SBB) for the evaluation of celiac disease as the cause of IDA
      is not routinely recommended. The aim of the present study was to determine the
      yield of SBB performed during routine endoscopy of adults with IDA. METHODS: We
      prospectively studied 93 patients with IDA. Three control groups were included:
      23 patients with steatorrhea, 37 patients with idiopathic diarrhea, and 9
      patients in whom SBB was performed for miscellaneous indications. RESULTS: Eleven
      patients with IDA and two patients with steatorrhea had SBB findings compatible
      with celiac disease. None of the patients from the other two groups had similar
      findings. Two patients with IDA, who were later diagnosed to suffer from celiac
      disease, presented: one with occult blood in the stool and the other with rectal
      bleeding. Subgroup analysis of patients with IDA revealed that patients with
      celiac disease were younger, had significantly more episodes of diarrhea, lower
      mean hemoglobin level, and longer duration of anemia than those without celiac
      disease. Other mucosal abnormalities were found in a substantial number of
      patients with celiac disease: esophagitis, gastritis, duodenitis, hemorrhoids,
      and colitis. CONCLUSIONS: A substantial number of adult Israeli patients who
      present with IDA are found, on SBB, to have mucosal abnormalities compatible with
      the diagnosis of celiac disease. The presence of esophagitis, gastritis, or
      duodenitis on esophagogastroduodenoscopy, or other abnormalities on colonoscopy,
      do not exclude the coexistence of celiac disease. Celiac disease should be
      included and routinely looked for in the differential diagnosis of adult patients
      with IDA.

PMID- 8855730
TI  - Clinical implications of the white nipple sign and its role in the diagnosis of
      esophageal variceal hemorrhage.
AB  - OBJECTIVE: Differentiation of esophageal variceal hemorrhage from other sources
      of the GI tract is often difficult. This is a prospective investigation of the
      significance of the white nipple sign in patients with recent esophageal variceal
      hemorrhage. METHODS: One hundred sixty-six patients with recent variceal
      hemorrhage were prospectively studied with respect to presence or absence of the
      white nipple sign and other stigmata of hemorrhage and compared with 100 patients
      with known varices but without a clinical history of bleeding. RESULTS: The white
      nipple sign correlated positively with severity of bleeding (patients required
      more blood transfusion), hematemesis, and signs of shock. Patients with the white
      nipple sign also tended to undergo emergency endoscopy and have active bleeding
      at the time of endoscopy. There was no correlation between rebleeding rate after
      endoscopic therapy and presence of the white nipple sign. Appearance of the white
      nipple sign was closely related to the timing of endoscopy (p < 0.0001). The
      sensitivity and specificity of the white nipple sign in the diagnosis of
      esophageal variceal hemorrhage were 21 and 100%, respectively, compared with 100
      and 54% for the red color sign. Furthermore, the sensitivity of the white nipple
      sign increased with shorter times between bleeding and endoscopy. CONCLUSIONS: In
      patients with upper GI bleeding, the white nipple sign suggests that the varices
      bled recently and that the bleeding was severe. However, it has no predictive
      value for rebleeding after endoscopic therapy. Earlier endoscopy (i.e., within 24
      h of bleeding) is suggested to improve the diagnostic rate of esophageal variceal
      hemorrhage.

PMID- 8855731
TI  - Prolonged ambulatory pH monitoring in patients with persistent gastroesophageal
      reflux disease symptoms: testing while on therapy identifies the need for more
      aggressive anti-reflux therapy.
AB  - Patients with gastroesophageal reflux disease (GERD) who remain symptomatic
      despite receiving a moderate dose of a proton pump inhibitor need accurate
      assessment to determine who will respond to high doses of the drug or even need
      surgery. AIM: To determine if prolonged ambulatory pH monitoring performed in
      patients with persistent symptoms potentially due to GERD while on therapy could
      predict which patients are likely to benefit from more aggressive anti-reflux
      therapy. METHODS: Ambulatory pH studies were reviewed for 45 patients with
      continuing reflux-type symptoms while on 20 mg omeprazole b.i.d. Patients were
      separated by typical symptoms (heartburn) versus atypical symptoms (chest pain,
      asthma, hoarseness, cough, throat burning) and for degree of symptom association
      with episodes of reflux during pH monitoring (symptom index). Control of
      esophageal acid exposure by omeprazole was defined as distal esophageal pH < 4 <
      1.6% total time. RESULTS: Of these 45 patients, 14 (31%) had acid reflux that was
      not controlled by omeprazole 20 mg b.i.d. Thirty-six patients had atypical
      symptoms of GERD, and 10 of these patients had poorly controlled reflux. Of these
      10 patients, only one patient responded to omeprazole 20 mg q.i.d. In the other
      nine patients, omeprazole at the higher dose controlled the reflux (documented by
      pH monitor), but symptoms persisted with poor association to reflux. Thus, only
      one out of 36 patients with atypical symptoms had subsequent improvement in
      symptoms. Nine patients had persistent, typical GERD symptoms, and five of these
      patients had poorly controlled GER. The three patients with good symptom
      correlation and poorly controlled reflux all responded to increased omeprazole
      whereas the two with poor symptom association did not. One patient with good
      control of reflux but good correlation of the remaining reflux to persistent
      symptoms also responded symptomatically to 80 mg of omeprazole. CONCLUSION: By
      assessing symptom correlation to reflux episodes and control of reflux by
      therapy, ambulatory pH monitoring performed in patients with persistent symptoms
      potentially due to reflux while on therapy gives valuable information concerning
      further treatment strategies.

PMID- 8855732
TI  - Parietal cell hyperactivity is not due to Helicobacter pylori infection in
      patients with duodenal ulcer.
AB  - OBJECTIVE: To determine the relationship between Helicobacter pylori infection
      and parietal cell mass and functional status in 10 patients with duodenal ulcer
      and 22 patients with functional dyspepsia. METHODS: We measured pentagastrin
      stimulated acid secretion, determined the activity status of parietal cells on
      the basis of ultrastructural morphological features, and measured parietal cell
      mass and canalicular area with computerized densitometric morphometry. The number
      of antral G cells per square millimeter of mucosa was estimated
      inmunohistochemically, and basal serum gastrinemia was determined. RESULTS: In
      patients with duodenal ulcer, acid secretion, the percentage of activated
      parietal cells, and canalicular area were increased, but there was no difference
      between patients and dyspeptic controls in parietal cell mass. Helicobacter
      pylori infection did not modify these parameters, although it was associated with
      basal hypergastrinemia. CONCLUSION: In patients with duodenal ulcer, parietal
      cells display functional hyperactivity, which causes hypersecretion of acid; this
      effect is apparently unrelated to Helicobacter pylori infection.

PMID- 8855733
TI  - Helicobacter pylori does not migrate from the antrum to the corpus in response to
      omeprazole.
AB  - BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo.
      One opinion is that H. pylori "migrates" from the antrum to the corpus in
      response to omeprazole therapy. METHODS: To determine whether H. pylori migrates
      in response to omeprazole, we assessed the presence of H. pylori in the antrum
      and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and
      histological examination of antral biopsies (Genta stain) were performed before
      patients received omeprazole, at the end of therapy, and 4-6 wk later. The end
      points were presence or absence of H. pylori and the number of H. pylori colonies
      per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and
      corpus at entry and 4-6 wk after ending therapy. Three general patterns were
      prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%),
      antrum-negative and corpus-positive (24%), both antrum- and corpus-negative
      (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation
      of the number of colonies per biopsy in those who remained H. pylori-positive in
      both the antrum and corpus throughout showed that the number of H. pylori
      decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/-
      51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus,
      respectively, and tended to return to pre-therapy levels 4-6 wk later. The number
      of H. pylori in the corpus also decreased in the antrum-negative and corpus
      positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p <
      0.05). In most of the patients studied, the number of H. pylori in the corpus was
      less posttreatment than it was pretreatment. The decrease in H. pylori load was
      also reflected in the development of false-negative urea breath tests.
      CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the
      corpus; migration from the antrum to the corpus in response to omeprazole is a
      myth.

PMID- 8855734
TI  - Diagnostic tests for Helicobacter pylori: a prospective evaluation of their
      accuracy, without selecting a single test as the gold standard.
AB  - OBJECTIVE: To assess the accuracy of six commonly used diagnostic tests for
      Helicobacter pylori in a prospective study without using any specific test as the
      gold standard (the patient was regarded as H. pylori-infected if two or more
      tests, whatever their nature, were positive). METHODS: In 105 outpatients
      undergoing upper GI endoscopy, 62 without significant abnormalities, 28 with
      gastroesophageal reflux disease, 19 with peptic ulcer, one with erosive
      gastritis, and one with atrophic gastritis (some patients had more than one
      diagnosis), antral biopsy specimens were taken for culture, polymerase chain
      reaction, histological examination (hematoxylineosin and Giemsa stains), and
      rapid urease test. Corpus biopsy specimens were taken for histological
      examination. Serology (ELISA) and a 13C-urea breath test were also performed.
      Consistency of diagnosis between two pathologists was assessed by kappa
      statistics. RESULTS: Sensitivity and specificity, respectively, were as follows:
      culture, 98.4 and 100%; polymerase chain reaction, 96.7 and 100%; histological
      examination (antrum), 96 and 98.8%; histological examination (antrum + corpus),
      98.4 and 98.8%; rapid urease test, 90.2 and 100%; 13C-urea breath test, 100 and
      100%; and serological examination, 98.4 and 88.4% (95% in those who had not been
      previously treated for H. pylori). All H. pylori-positive cases were detected by
      culture and rapid urease test. In 86.4% of these cases all antral biopsy-based
      tests were positive. Agreement between pathologists was good, with a kappa
      coefficient around 0.90 for antral biopsy specimens. CONCLUSIONS: All antral
      biopsy-based tests, as well as the 13C-urea breath test, are accurate for the
      diagnosis of H. pylori infection. Sampling error is a problem of minor
      importance. The lower specificity of serological tests may be largely explained
      by previous treatment of H. pylori.

PMID- 8855735
TI  - Etiological involvement of Helicobacter pylori in "reflux" gastritis after
      gastrectomy.
AB  - OBJECTIVES: "Reflux" gastritis after gastrectomy is associated with various
      symptoms that are often detrimental to the patients' quality of life. However,
      prevention of the reflux does not always bring relief from the symptoms of
      gastritis. Helicobacter pylori (H. pylori) is now considered one of the most
      important pathogenetic factors in gastritis. The association between H. pylori
      infection and reflux gastritis after gastrectomy was investigated in the present
      study. METHODS: In total, 115 patients who had undergone gastrectomy were entered
      in this study. Five biopsy specimens from the gastric remnant were taken during
      upper GI endoscopy. One specimen was examined pathohistologically, and the
      remaining four were examined for H. pylori infection. The histological degree of
      gastritis was determined according to the score system of Rauws et al. RESULTS:
      Forty-six patients (40%) demonstrated H. pylori infection in their stomachs. The
      prevalence of the infection was significantly higher in patients with
      conventional gastrectomy than in those with subtotal gastrectomy. The prevalence
      of H. pylori infection was significantly lower in patients who had undergone
      gastrectomy more than 4 yr ago. The histological gastritis score in patients with
      H. pylori infection was significantly higher than in those without H. pylori
      infection. Furthermore, the eradication of H. pylori in patients with both
      serious gastritis symptoms and no bile reflux improved the symptoms and
      significantly decreased the histological gastritis score. CONCLUSIONS: The
      results suggest that H. pylori is a factor in the pathogenesis of reflux
      gastritis after gastrectomy.

PMID- 8855736
TI  - Helicobacter pylori infection and blood group antigens: lack of clinical
      association.
AB  - OBJECTIVES: Blood group antigens traditionally have been associated with a risk
      of developing peptic ulcer and gastric cancer. Helicobacter pylori is a bacterium
      associated with chronic active gastritis and ulcer disease, and its attachment to
      gastric mucosa was recently shown in vitro to be mediated by blood group Lewisb
      and H antigens. This study was designed to test the clinical relevance of this
      laboratory observation in patients undergoing endoscopy and gastric biopsy.
      METHODS: Blood group phenotypes and gastric biopsies for H. pylori and histology
      were determined and correlated in 384 patients undergoing upper endoscopy. Blood
      from healthy blood donors was tested for the same blood group antigens and used
      as a control group. RESULTS: The distribution of blood groups ABO, Lewis, Rhesus,
      and MN was similar among the patients undergoing endoscopy and a control group of
      2369 healthy blood donors from the same geographic area. There was no correlation
      between H. pylori infection or the H. pylori-associated diseases, peptic ulcer or
      chronic active gastritis, with any blood group phenotype, including Lewisb, blood
      group O, or both. CONCLUSION: No in vivo correlation between H. pylori infection
      or disease and Lewisb or H antigen could be demonstrated. Moreover, patients with
      H. pylori infection and disease have a distribution of blood group antigens
      similar to a control population.

PMID- 8855737
TI  - Omeprazole and clarithromycin with and without metronidazole for the eradication
      of Helicobacter pylori.
AB  - OBJECTIVES: To treat previously untreated adult patients infected with
      Helicobacter pylori with one of two regimens in an ambulatory community setting
      to assess the efficacy and safety of these regimens. METHODS: Sixty five adult
      patients with histologically confirmed H. pylori infection were randomly assigned
      in this open cohort study to 2 wk, low dose, twice daily treatment with
      omeprazole 20 mg and clarithromycin 250 mg (OC) (n = 31) or OC plus metronidazole
      500 mg (OCM) (n = 34). At least 4 wk after treatment, H. pylori status was
      assessed by histology (four gastric biopsies, two each from antrum and body).
      RESULTS: Triple therapy with OCM was significantly better than dual therapy with
      OC in intent-to-treat (82.4 vs 58.1%, p = 0.03) and per protocol analysis (93.3
      vs 62.1%, p = 0.004). Although there were frequent side effects (OC 19/31 61.3%;
      OCM 22/34 64.7% with at least one side effect), these were generally mild, and
      patients were able to complete nearly all of their medications (OC 97.2%, OCM
      96.7% of pills taken). The only patient withdrawn due to medication side effects
      was in the OC arm. CONCLUSIONS: Triple therapy with OCM in a community setting
      eradicates H. pylori more effectively than dual therapy with OC. OCM is tolerated
      with high compliance despite frequent minor side effects and appears safe without
      the development of serious adverse events.

PMID- 8855738
TI  - Long-term prognosis of chronic hepatitis C after treatment with interferon alpha
      2b and characterization of incomplete responders.
AB  - OBJECTIVES: During the long-term follow-up of chronic hepatitis C patients
      treated with interferon alpha-2b, we have identified some patients who had
      continuous normalization, or transient elevation of the serum alanine
      aminotransferase levels within the first 6 months of follow-up and subsequent
      normalization, but HCV RNA was still found to be positive during the follow-up
      period (incomplete responder; ICR). We wished to clarify the characteristics of
      these patients, and to investigate the factors predictive of the response to
      interferon. METHODS: Seventy patients were treated with 6 MU of rIFN alpha-2b,
      three times weekly for 24 wk. Sixty-six patients (94%) completed the entire
      therapy and 2-yr follow-up protocol. RESULTS: Twenty-four months after cessation
      of IFN treatment, 24 patients (36%) were defined as complete responders (CR;
      continuously normal alanine aminotransferase levels, and HCV RNA negative). Nine
      patients (14%) were defined as ICR. Thirty-three patients (50%) were defined as
      nonresponders (NR). Compared with the CR or NR groups, the patients in the ICR
      group tended to have the mildest histological severity and lowest histological
      activity index scores, but there were no significant differences in any of the
      other histological features. The complete response rate was significantly higher
      in patients with low concentration of HCV RNA, and genotypes other than type II.
      CONCLUSIONS: After long-term follow-up of the 66 patients, 24 patients (36%) were
      CR, nine (14%) were ICR, and 33 (50%) were NR. The histological stage and indices
      of chronic hepatitis may help to predict a patient's response to IFN therapy.

PMID- 8855739
TI  - Core promoter mutations of hepatitis B virus for the response to interferon in e
      antigen-positive chronic hepatitis B.
AB  - OBJECTIVES: Mutations in the precore region are not always detected in hepatitis
      B virus (HBV) from patients with chronic hepatitis B who respond to interferon
      and lose hepatitis B e antigen (HBeAg) from serum. The other mutations may also
      be responsible for the loss of HBeAg and response. METHODS: Forty six consecutive
      patients with HBeAg-positive chronic hepatitis B received recombinant-alpha 2 a
      interferon (total dose: 702 MU). The mutation for stop codon 28 in the precore
      region was determined by restriction fragment length polymorphism, and mutations
      in the core promoter were searched for in five HBV DNA clones propagated from
      each patient. RESULTS: HBeAg was cleared at 6 months after interferon in 11 (61%)
      of 18 patients with the precore mutation and in 12 (43%) of 28 without it. Of
      these 28 patients, 19 with mutations in the core promoter in all five HBV DNA
      clones lost HBeAg more frequently than the remaining nine who had at least one
      clone among the five that lacked such mutations (58 vs 11%, p < 0.05).
      CONCLUSIONS: HBeAg-positive patients infected with HBV variants having mutations
      for an HBeAg-negative phenotype would respond better to interferon by clearing
      HBeAg from serum. Such mutations may not necessarily be in the precore region but
      also in the core promoter, which would interfere with the synthesis and secretion
      of HBeAg either at the translation or transcription level.

PMID- 8855740
TI  - Life events and daily hassles in patients with atypical chest pain.
AB  - The impact of major life events and daily hassles on atypical chest pain is
      unknown. The aim of the present study was to investigate the relationship of the
      occurrence and perception of major life events and daily hassles in atypical
      chest pain patients. Five groups of subjects were studied. They were healthy
      controls, atypical chest pain patients without motility/reflux changes, atypical
      chest pain patients with motility/reflux changes, dyspeptic patients, and
      patients with chronic obstructive airway disease/peptic ulcer/gallstone. A
      questionnaire concerning the occurrence and perception of major life events and
      daily hassles was administered to all five groups of subjects. Using analysis of
      variance, we found that atypical chest pain patients without underlying
      motility/reflux changes had significantly higher scores of negative life events
      and total life events than healthy controls, atypical chest pain patients with
      underlying motility/reflux changes, and patients with chronic obstructive airway
      disease/peptic ulcer/gallstone. There were no significant differences between
      atypical chest pain patients without underlying motility/reflux changes and
      patients with dyspepsia in terms of the number of negative life events, negative
      scores, number of positive life events, positive scores, and total life events.
      Discriminate analysis identified five of the 47 major life events (major changes
      in sleeping habits, change in work situation, major changes in financial status,
      retirement, and suffering from severe illness or injury) to be useful for
      discriminating atypical chest pain patients without underlying motility/reflux
      changes from the healthy controls and from atypical chest pain patients with
      underlying motility/reflux changes. The overall correct classification rate was
      81.8%. In conclusion, psychological factors, such as perception of negative life
      events and occurrence and perception of daily hassles, may play a role in the
      pathogenesis of atypical chest pain.

PMID- 8855741
TI  - Management of severe ulcerative colitis with the help of high resolution
      ultrasonography.
AB  - OBJECTIVES: The prognosis of attacks of ulcerative colitis is clearly linked to
      the extent and activity of the disease. The aim of this study was to investigate
      the value of high resolution ultrasonography in assessing both the extent and
      activity of severe ulcerative colitis and its response to medical treatment.
      METHODS: Fifty-seven consecutive patients affected by a severe (32 patients) or
      moderately severe (25 patients) attack of ulcerative colitis underwent
      ultrasonographic examination. The ultrasonographic extent of the disease was
      evaluated in 32 patients by comparing ultrasonography and scintigraphy. RESULTS:
      Compared with scintigraphy, sensitivity, specificity, and overall accuracy of
      ultrasonographic extent were 89%, 100%, and 91%, respectively. These results were
      also confirmed in a subgroup of patients submitted to surgery, comparing
      ultrasonographic and scintigraphic data versus specimens. Using the
      ultrasonographic score of activity, it was possible to discriminate severe and
      moderately severe attacks with a specificity, sensitivity, and diagnostic
      accuracy of 96%, 90.3%, and 92.9% respectively. A close correlation was also
      found between ultrasonographic and scintigraphic activity (r = 0.78; p < 0.001).
      After 10 days of intensive treatment, the ultrasonographic activity significantly
      decreased in severe and moderate groups (p < 0.001) and in both subgroups of
      nonoperated patients (p < 0.001) but not in operated patients (p = NS).
      CONCLUSIONS: High resolution ultrasonography can be useful in assessing both
      extent and activity of severe ulcerative colitis, in monitoring the patient's
      condition, and in objectively evaluating the response to medical therapy.

PMID- 8855742
TI  - Endoscopic variceal ligation versus endoscopic injection sclerotherapy:
      comparison of hepatic and renal function.
AB  - OBJECTIVES: The aim of the present study was to compare the safety of endoscopic
      variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) in terms of
      liver and kidney functions in patients with liver cirrhosis. METHODS: Forty-four
      patients admitted to Takatsuki General Hospital between February 1991 and March
      1993 with esophageal varices due to liver cirrhosis were randomly assigned to
      receive either EVL or EIS. Serum levels of AST, ALT, total bilirubin (T-bil),
      direct bilirubin (D-bil), prothrombin time (PT), hepaplastin test (HPT),
      antithrombin III (ATIII), creatinine (Cr), and blood urea nitrogen (BUN) were
      measured before and 24 h, 3 days, 7 days, and 14 days after both forms of
      therapy. RESULTS: Significant elevations of serum T-bil, serum D-bil, and serum
      ALT and AST levels were observed in the EIS group but not in the EVL group. No
      significant increases of serum PT, HPT, ATIII, BUN, or Cr levels were observed
      after treatment in either group. CONCLUSION: EVL should be considered a first
      choice therapy for eradicating esophageal varices.

PMID- 8855743
TI  - Jejunostomy tube placement in refractory diabetic gastroparesis: a retrospective
      review.
AB  - OBJECTIVES: Severe diabetic gastroparesis leading to recurrent episodes of
      diabetic ketoacidosis and frequent hospitalizations can be among the most
      disabling of all diabetic complications. Surgical placement of a jejunostomy tube
      (J-tube) beyond the affected stomach to deliver fluid, nutrients, and medication
      is one of the few therapeutic options remaining in the cohort of patients who
      have failed standard medical therapy. This study attempts to define the natural
      history of refractory diabetic gastroparesis and the risks and benefits of J-tube
      placement. METHODS: A total of 26 patients with diabetic gastroparesis requiring
      J-tube placement were identified between 1980 and 1994. Medical chart review and
      telephone follow-up were performed using standardized questionnaires. RESULTS:
      All patients had documented delayed gastric emptying, had failed medical therapy,
      and had been hospitalized on multiple occasions. Neuropathy, retinopathy, and
      nephropathy were observed in 88%, 81%, and 65% of patients, respectively. The
      mean duration of study follow-up was 47 months (1-130 months). The mean age of
      subjects at the time of J-tube placement was 31 yr, and a preponderance of female
      patients (73%) was noted. There were 23 major complications in 14 patients
      requiring surgery or hospitalization and 47 minor complications in 21 patients
      managed on an outpatient basis. The mean duration of J-tube use was 20 months.
      There were 10 deaths during follow-up, one related to J-tube placement.
      Retrospectively, 39% reported improved symptoms of nausea/vomiting (4% worsened),
      52% reported fewer hospitalizations (4%, more frequent), 56% reported improved
      nutritional status (4% worsened), and 83% reported improved overall health (4%
      worsened) after J-tube placement. The improvement in overall health status was
      the only symptom that reached statistical significance. CONCLUSION: Severe
      refractory gastroparesis is associated with multiple hospitalizations, a high
      incidence of concomitant diabetic complications, and a mortality rate of 38% at 4
      yr. There is a high incidence of complications following J-tube placement in this
      population. Despite this, most patients retrospectively reported improved overall
      health after J-tube placement. Therefore, placement of a J-tube may be a workable
      option with acceptable perioperative morbidity and mortality rates in selected
      patients with severe diabetic gastroparesis who have failed medical therapy. A
      prospective study of J-tube placement and other available means of nutritional
      support is needed to demonstrate further the efficacy of this intervention in
      patients with severe diabetic gastroparesis.

PMID- 8855744
TI  - Endoscopic biliary stenting for the palliation of pancreatic cancer: results,
      survival predictive factors, and comparison of 10-French with 11.5-French gauge
      stents.
AB  - OBJECTIVES: To compare the efficacy and complications of different stent lengths
      and diameters in the palliation of jaundice caused by pancreatic cancer, as well
      as investigate survival predictive factors and the success of endoscopic therapy.
      METHODS: This study summarizes our results with 103 pancreas cancer patients
      treated by endoscopic plastic biliary stenting, of whom 87 were followed up until
      death or the time of writing. Before therapy, bilirubinemia, tumor primary size,
      presence of distant metastases, and signs of duodenal involvement were evaluated
      as prognosis risk factors. In a retrospective, nonrandomized fashion, we compared
      the efficacy and complications (especially clogging) of 10-French versus 11.5
      French gauge stents and of "short" (< or = 8 cm) versus "long" (> or = 9 cm)
      prostheses. RESULTS: Thirty six men and 51 women (median age 74 yr) with
      pancreatic cancer were analyzed. Stenting could abolish jaundice or make it
      imperceptible (bilirubinemia < 3 mg %) in 74 patients (85%). Median bilirubinemia
      after treatment decreased from 13.9 mg/dl to 1.0 mg/dl. Hospital mortality was
      2.7%. The commonest long term complication was clogging, which occurred 66 times
      in 33 patients. Median stent patency was 3 and 4 months for 10-F gauge and 11.5-F
      gauge stents, respectively (p > 0.05). When analyzing the patients who were alive
      6 months after therapy, the clogging rate was 46% and 55% for 10-F and 11.5-F
      stents, respectively (p > 0.05). The length also did not influence stent patency.
      The only risk factor assessed before therapy, which independently predicted
      survival, was the presence of distant metastases. Median survival for patients
      with metastatic disease was 2.5 months and 9 months for those without metastases
      (p = 0.0015). CONCLUSIONS: We conclude that 10-F and 11.5-F stents have the same
      efficacy in the palliative management of malignant obstructive jaundice due to
      cancer of the pancreas. Detection of distant metastases is the best outcome
      predictive factor in these patients and should be regarded as a restriction to
      the insertion of biliary metal stents.

PMID- 8855745
TI  - Does gallstone formation after open cardiac surgery result only from latent
      hemolysis by replaced valves?
AB  - OBJECTIVES: To clarify the relationship between open heart surgery and gallstone
      formation. METHODS: Fifty-one patients without gallstones (Group A) underwent
      cardiac surgery using a heart-lung machine and were followed for 24 months by
      ultrasonography. Blood tests of hemolysis markers were examined before,
      immediately after, and 3, 6, and 12 months after surgery. And 52 healthy
      candidates without gallstone (Group B) also were followed for 24 months. RESULTS:
      The cumulative gallstone incidence in Group A was 15.7% at 3 months after
      surgery, 23.9% at 6 months, and 30.4% at and beyond 12 months and was
      significantly higher than that of Group B (p < 0.01). The stones showed a high
      dense pattern, indicative of pigment stones, in eight of the 10 patients assessed
      by CT. With respect to the type of surgery, latent hemolysis was seen only in
      patients who underwent mechanical valve replacement. However, there were no
      significant differences in the gallstone incidence between the patients who
      underwent mechanical valve replacement and those who underwent another cardiac
      surgery. The values of hemoglobin, haptoglobin, and lactate dehydrogenase showed
      abnormal values immediately after surgery, regardless of mechanical valve
      replacement or another cardiac surgery. CONCLUSIONS: The use of a heart-lung
      machine, which produces hemolysis, appears to have a close relation to gallstone
      formation after open cardiac surgery.

PMID- 8855746
TI  - Nitrate kinetics in patients with compensated cirrhosis: correlation with
      hemodynamics.
AB  - OBJECTIVES: The serum nitrate concentration is known to be increased in patients
      with cirrhosis. This study was designed to determine the kinetics of nitrate in
      the splanchnic vascular areas and its relationship with hepatic hemodynamics in
      patients with compensated cirrhosis. METHODS: We measured the serum nitrate
      concentration of various sites, including the femoral artery, hepatic vein,
      azygos vein, and pulmonary artery, and compared these values with hepatic
      hemodynamics. RESULTS: The nitrate concentrations of hepatic vein and azygos vein
      were significantly greater in cirrhotic patients compared with those of control
      subjects. The values were particularly elevated in patients with Child-Pugh's
      class B. In control subjects, hepatic vein and azygos vein nitrate concentrations
      were significantly lower than arterial nitrate concentrations whereas nitrate
      concentrations were significantly greater in the hepatic and azygos veins than
      femoral artery in cirrhotic patients, and nitrate kinetics was that of the net
      release of nitrate from the hepatic and azygos veins. The portal vein blood flow
      positively correlated with the nitrate concentration of azygos vein, pulmonary
      artery, and femoral artery. CONCLUSIONS: The present results implicate the
      enhanced production of nitric oxide in the mesenteric vascular beds in patients
      with cirrhosis. The positive correlation between portal vein blood flow and serum
      nitrate concentrations suggests that endogenous nitric oxide may have an
      important role in the regulation of portal hemodynamics in these patients.

PMID- 8855747
TI  - Primary signet ring cell carcinoma of colorectum: an age- and sex-matched
      controlled study.
AB  - OBJECTIVE: To evaluate the differences of clinicopathological features between
      colorectal signet ring cell carcinoma and ordinary adenocarcinoma. METHODS: The
      clinicopathological data of 28 cases with primary colorectal signet ring cell
      carcinoma was reviewed and compared with the data from 56 age- and sex-matched
      patients with ordinary adenocarcinoma. RESULTS: Fifteen cases (53.5%) with
      primary signet ring cell carcinoma were younger than 40 yr of age. Compared with
      985 ordinary adenocarcinoma cases, signet ring cell carcinoma is present in
      excess in younger patients (p < 0.005). Further comparison with 56 age- and sex
      matched ordinary adenocarcinomas showed that signet ring cell carcinomas could
      affect any sites of colon, presented as scirrhous appearance more frequently, had
      a higher percentage of stage III or IV tumors (78.6 vs 48.2%, 14.3 vs 7.2%, p <
      0.005), had a higher rate of peritoneal seeding (35.7 vs 12.5%, p < 0.005) but a
      lower rate of liver metastasis (14.3 vs 32.1%, p < 0.005), and had a lower
      curative resection rate (64.2 vs 80.4%, p < 0.005) and a higher local or distant
      metastasis rate (61.1 vs 17.8%, p < 0.05). Survival with signet ring cell
      carcinoma is lower than that of ordinary adenocarcinoma. "Stage-on-diagnosis" and
      "presence of subsequent distant metastasis" were the major factors influencing
      survival of signet ring cell carcinoma patients. CONCLUSION: The delay in
      diagnosis reduces the chance of curative resection, increases the possibility of
      local or distant metastasis postoperatively, and, thus, shortens the survival
      chances. To improve outcome, recognition of the factors responsible for this
      delay should be stressed so that this tumor may be found at a stage when cure is
      possible.

PMID- 8855748
TI  - Three histologically different tiny gastric cancers developing adjacent to each
      other, resected endoscopically in a single mucosal piece.
AB  - In this report, we describe a case with triple tiny cancers of the stomach
      developing adjacent to each other and resected endoscopically in a single mucosal
      piece. The three cancers differed from each other histologically. The surrounding
      mucosa was atrophic pyloric gland mucosa with moderate to severe intestinal
      metaplasia. Both histological and serological examinations were negative for
      Helicobacter pylori. Each of the three cancer lesions was positive for mutant p53
      product immunohistochemically. None of the cancers were positive for Epstein-Barr
      virus sequence in an in situ hybridization analysis. These lesions suggest that
      certain local conditions in the gastric mucosa can result in carcinogenesis of
      different histological types of gastric cancers.

PMID- 8855749
TI  - Clinical, pathological, and antibody pattern of latent celiac disease: report of
      three adult cases.
AB  - We report the clinical, pathological, and serological findings of three adult
      patients with latent celiac disease. The initial intestinal biopsies, which were
      normal, were carried out in the first case during an upper gastrointestinal
      endoscopy performed for a duodenal ulcer, in the second case for first-degree
      familiarity with a celiac patient, and in the third case because of the presence
      of malabsorption symptoms. In all three cases, intraepithelial lymphocytes were
      within the normal range in the first biopsy and cannot, therefore, be considered
      as a marker of latent celiac disease. In only two of the three patients was it
      possible to carry out the search for the serum antibodies connected with celiac
      disease at the time of the first biopsy. In both these cases, the antijejunal
      antibodies were present before the development of the intestinal lesions.

PMID- 8855750
TI  - Small bowel fistulae in Degos' disease: a case report and literature review.
AB  - Degos' disease (malignant atrophic papulosis) is a rare, progressive, small- and
      medium-size arterial occluding disease, leading to tissue infarction and
      initially involving the skin. We report a case with bowel involvement followed by
      enterocutaneous fistulae. Diagnostic laparoscopy with jejunal biopsy was followed
      by jejunal perforations, peritonitis, and fistulae leading to death after a 4
      month course in the intensive care unit. The usual treatment of enterocutaneous
      fistula by somatostatin and parenteral nutrition was ineffective in this case.
      The course of the disease in our patient was not usual, as can be seen in a
      literature review underlining the specific features of Degos' disease.
      Laparoscopy and bowel biopsy should be avoided in this context. Degos' disease
      should be considered in the differential diagnosis of a primary ulceration of the
      small intestine.

PMID- 8855751
TI  - Early migration of a covered self-expanding metal stent corrected by implantation
      of a second stent.

PMID- 8855752
TI  - Intractable cough and abnormal pulmonary function in benign recurrent
      intrahepatic cholestasis.
AB  - Benign recurrent intrahepatic cholestasis (BRIC) is a syndrome characterized by
      recurrent episodes of cholestasis with associated pruritus. The intensity and
      duration of cholestatic episodes, and the length of the intervening periods, vary
      unpredictably. We report the case of a patient with BRIC who was incapacitated by
      a severe intractable cough that accompanied marked pruritus during her second
      cholestatic episode. No cause for the cough was found, and it resolved
      spontaneously with amelioration of mild restrictive abnormalities of pulmonary
      function as the cholestasis subsided. Although cough has not been recognized as a
      complication of cholestasis, we postulate that it may occur either (i) as a
      result of direct stimulation of sensory nerves by circulating humoral substances
      related to the cholestasis that act either peripherally in the airways or
      centrally, or (ii) through stimulation of the vagus nerve in the liver, leading
      to cough that is mediated either centrally or by reflex.

PMID- 8855753
TI  - Bacillary angiomatosis associated with extensive esophageal polyposis: a new
      mucocutaneous manifestation of acquired immunodeficiency disease (AIDS).
AB  - Bacillary angiomatosis is a rare infection that has been associated with human
      immunodeficiency virus infection. The causative organism is Rochalimaea henselae
      and contact with cats is a risk factor. We present a case of a 37-yr-old man who
      had recent prolonged exposure to a cat and presented with fever, iron deficiency
      anemia, and guaiac-positive stools who had biopsy-proven bacillary angiomatosis
      skin lesions and on esophagogastroduodenoscopy had multiple, diffuse, friable,
      polypoid lesions in the esophagus. The histology of the esophageal polyps was
      identical to the skin lesions, and the polyps disappeared after treatment with
      erythromycin. Bacillary angiomatosis should be included in the differential
      diagnosis of infectious upper gastrointestinal manifestations associated with
      AIDS.

PMID- 8855754
TI  - Olfactory stimuli provoke diffuse esophageal spasm: reversal by ipratropium
      bromide.
AB  - Diffuse esophageal spasm (DES) is a motor disorder of the esophageal smooth
      muscle characterized by multiple spontaneous contractions and by swallow-induced
      contractions that are of simultaneous onset, large amplitude, long duration, and
      repetitive occurrence. Although the pathogenesis of DES is unknown, provocative
      studies with cholinergic stimulation, esophageal balloon distention, or acid
      instillation have suggested involvement of both sensory and motor mechanisms.
      This report describes a patient with DES who would predictably become symptomatic
      with dysphagia and chest pain upon inhalation of perfume or other strong odors.
      Using esophageal scintigraphy to quantitate and analyze esophageal transit in
      this patient, we report for the first time that olfactory stimulation triggers
      episodes of DES and that such phenomena are mediated through the vagus nerve,
      because they can be ameliorated by the administration of ipratropium bromide.
      These observations suggest a new (sensory) pathway for the induction of DES and
      raise the intriguing possibility that inhaled anticholinergics may have a
      therapeutic role in the management of spastic esophageal motility disorders.

PMID- 8855755
TI  - Cyclic vomiting: association with multiple homeostatic abnormalities and response
      to ketorolac.
AB  - Cyclic vomiting is a rare syndrome that over the years has variously been
      ascribed to psychogenic causes, sensory seizures, abdominal migraine, and more
      recently, to mechanical or electrical disturbances in gastric physiology. We
      describe the case of a 65-year-old white diabetic female with a 10-yr history of
      recurrent episodes of nausea and vomiting, occurring every 10-12 days and lasting
      approximately 1-3 days at a time. These episodes were accompanied by edema, mild
      temperature elevations, and remarkable elevations in blood pressure. In between
      these episodes, the patient remained asymptomatic. Initial screening tests were
      also negative except for moderate gastroparesis. However, antral motility was
      found to be normal, as was an electrogastrogram. Detailed neurological and
      psychiatric evaluations were negative. Trials of erythromycin, metoclopramide,
      naloxone, ondansetron, and amitryptiline were unsuccessful. Serial
      endocrinological testing revealed that an episode of vomiting was always preceded
      by an abnormal elevation in at least one of the following: serum
      adrenocorticotropic hormone, serum cortisol, or urinary cortisol. In the midst of
      an episode, all three values were exceedingly high (e.g., > 10-fold increases in
      24-hr urinary cortisol levels). Fluctuations of a milder degree, though still
      abnormally high, were also noted in between cycles at times when the patient was
      completely asymptomatic. High-dose dexamethasone suppressed these hormonal surges
      completely but not the clinical symptoms, which continued undisturbed. The
      patient was finally given a trial of intramuscular ketorolac during one of her
      episodes, which produced prompt and sustained relief. During the next few weeks,
      she was given this drug each time her symptoms commenced, and each time it
      appeared that her cycle had been aborted. She has since been able to terminate
      her episodes promptly and completely by self-administration of ketorolac. We
      speculate that her syndrome is caused by a poorly characterized disorder of
      endogenous prostaglandin release, resulting not only in derangements in the
      hypothalamic pituitary system but also in nausea and vomiting.

PMID- 8855756
TI  - Pemoline-induced autoimmune hepatitis.
AB  - We present a case of pemoline-induced autoimmune hepatitis in a 46-yr-old woman
      who received the drug for management of her multiple sclerosis. The autoimmune
      nature of the hepatitis is based on elevation of her anti-nuclear antibodies,
      anti-thyroid antibodies, IgA, and IgM globulins. These features of autoimmunity
      disappeared with normalization of her liver-associated enzymes and have remained
      negative for at least 6 months after completion of prednisone therapy.

PMID- 8855757
TI  - Endoscopic appearance of cryptosporidial duodenitis.
AB  - Cryptosporidial oocyst infection is a common cause of diarrhea in patients with
      AIDS. Concomitant symptoms can include crampy abdominal pain, nausea, vomiting,
      and anorexia. Esophagogastroduodenoscopy is then useful for delineating
      potentially treatable pathogens. We report a case of cryptosporidial duodenitis
      with characteristic endoscopic findings, biopsy correlate, and a review of the
      current literature. The endoscopic appearance illustrated strongly suggests
      proximal small bowel mucosal involvement with cryptosporidial oocysts.

PMID- 8855758
TI  - Concomitant onset of ulcerative colitis and autoimmune hemolytic anemia in an 83
      yr-old woman.

PMID- 8855759
TI  - Transjugular intrahepatic portosystemic shunt in the treatment of intermittently
      bleeding stomal varices.

PMID- 8855760
TI  - Acute appendicitis immediately after colonoscopy.
AB  - In a 69-yr-old man we treated, acute appendicitis occurred immediately after
      colonoscopy was performed. There were no signs or symptoms of appendicitis before
      colonoscopy, including in the colonoscopic findings around the cecal end and
      appendicular orifice. Because appendicitis is a rare complication of colonoscopy,
      prompt recognition should lead to early and effective treatment.

PMID- 8855761
TI  - Metastatic breast carcinoma presenting as obstructive jaundice.
AB  - A case of obstructive jaundice due to extrahepatic intraductal biliary metastasis
      from a breast carcinoma is reported. This clinical picture was a late
      manifestation and the first evidence of spread of the disease. The patient was
      treated by surgical decompression with relief of jaundice but died 5 months
      later. In patients with a history of carcinoma of the breast, the possibility of
      extrahepatic biliary metastasis should always be considered in the differential
      diagnosis of jaundice. Because this condition is amenable to palliation, it is
      important to differentiate it from jaundice due to hepatic involvement by this
      tumor.

PMID- 8855762
TI  - Vibrio cholerae 01 isolated in the gallbladder of a patient presenting with
      cholecystitis.
AB  - Cholera is a topical infection of the intestinal tract and rarely causes
      extraintestinal disease. The gallbladder has been proposed to be the reservoir of
      this organism. We present a patient from Bolivia who developed symptoms of acute
      cholecystitis and whose bile culture grew Vibrio cholerae 01 El tor.

PMID- 8855763
TI  - Primary lymphoma of the gallbladder; case report and review of the literature.
AB  - The term extranodal lymphoma refers to lymphoma arising in tissues other than
      lymph nodes or major lymphoid organs (1). The GI tract is commonly involved by
      lymphoma. Although lymphomas of the liver and the biliary tree are uncommon, they
      are well described in the literature. However, there are only nine cases of
      primary lymphoma of the gallbladder reported in the English literature. We report
      a patient with primary gallbladder lymphoma diagnosed preoperatively by
      ultrasound, with disease confined to the gallbladder on pathology specimens and
      radiological examination. His rapid disease progression to diffuse abdominal
      involvement in 6 wk points to the importance of a timely diagnosis. We postulate
      that delays in making the diagnosis may lead to the underdiagnosis of primary
      lymphoma of the gallbladder.

PMID- 8855764
TI  - Omeprazole to treat asthma?

PMID- 8855765
TI  - Nutritional hope or hype for short bowel syndrome?

PMID- 8855766
TI  - Percutaneous gastrostomy: a radiological alternative?

PMID- 8855767
TI  - Re: Alvarez et al., "Improvement of Thrombocytopenia due to Hypersplenism...".

PMID- 8855768
TI  - Breakthrough of interferon therapy.

PMID- 8855769
TI  - When should endoscopy be performed in patients with dyspepsia?

PMID- 8855770
TI  - Re: short-term treatment with lansoprazole.

PMID- 8855771
TI  - Jejunal diverticulitis.

PMID- 8855772
TI  - Enteroscopy and Peutz Jeghers syndrome.

PMID- 8855773
TI  - An unusual case of sarcoidosis presenting as a pancreatic mass.

PMID- 8855774
TI  - Cutaneous anergy to streptococcal antigens in Whipple's disease.

PMID- 8855775
TI  - Diagnose and treat Helicobacter pylori as any other infectious disease.

PMID- 8855776
TI  - Coal dust deposition--rare cause of "black esophagus".

PMID- 8855777
TI  - Intrathoracic incarceration of the colon after endoscopy.

PMID- 8855778
TI  - Acute renal failure associated with nonfulminant hepatitis A viral infection.

PMID- 8855779
TI  - Pitfalls of anticytokine autoantibody ELISA: false-positive results in Crohn's
      disease with hyperimmunoglobulinemia.

PMID- 8855780
TI  - Squamous cell papilloma of the esophagus.

PMID- 8855781
TI  - Clinical review 83: Mechanisms of glucocorticoid action in bone: implications to
      glucocorticoid-induced osteoporosis.

PMID- 8855782
TI  - Cytokines in primary hyperparathyroidism--factors that matter.

PMID- 8855784
TI  - Unusual causes of sellar/parasellar masses in a large transsphenoidal surgical
      series.

PMID- 8855783
TI  - Circulating levels of interleukin-6 and tumor necrosis factor-alpha are elevated
      in primary hyperparathyroidism and correlate with markers of bone resorption--a
      clinical research center study.
AB  - The pathogenesis of PTH-induced bone loss is uncertain. Experimental evidence
      suggests that PTH induces the production by osteoblasts of the bone-resorbing
      cytokine, interleukin-6. We measured the circulating levels of interleukin-6,
      tumor necrosis factor-alpha, and interleukin-1 beta and examined their
      relationship to biochemical markers of bone turnover in 38 patients with primary
      hyperparathyroidism (7 of whom also were studied after successful parathyroid
      adenomectomy), 6 patients with hypoparathyroidism, and 12 subjects with normal
      parathyroid function. The patients with untreated primary hyperparathyroidism had
      mean serum levels of interleukin-6 that were 16-fold higher than control values
      (mean +/- SEM; primary hyperparathyroidism 18.6 +/- 2.1 pg/mL, controls 1.1 +/-
      0.1; P < 0.001). Circulating levels of interleukin-6 soluble receptor (primary
      hyperparathyroidism 41.7 +/- 1.2 ng/ mL, controls 25.1 +/- 1.0; P < 0.001), and
      tumor necrosis factor-alpha (primary hyperparathyroidism 11.6 +/- 0.8 pg/mL,
      controls 2.5 +/- 0.2; P < 0.001) were also elevated. After successful parathyroid
      adenomectomy, levels of each of these cytokines fell into the normal range. The
      mean levels of interleukin-6, its soluble receptor, and tumor necrosis factor
      alpha in the subjects with hypoparathyroidism were lower than control values (P <
      0.001 for each variable). There was no difference between subjects with primary
      hyperparathyroidism and controls in the circulating level of interleukin-1 beta.
      In the subjects with untreated primary hyperparathyroidism, serum levels of
      interleukin-6 correlated strongly with those of intact PTH (r = 0.47, P = 0.003)
      and biochemical markers of bone resorption: serum deoxypyridinoline (r = 0.93, P
      < 0.001), serum type I collagen carboxyterminal telopeptide (r = 0.87, P <
      0.001), urinary pyridinoline (r = 0.81, P < 0.001), and urinary deoxypyridinoline
      (r = 0.63, P = 0.005). Levels of tumor necrosis factor-alpha correlated less
      strongly with the same variables: PTH (r = 0.41, P = 0.01), serum
      deoxypyridinoline (r = 0.48, P = 0.002), serum type I collagen carboxyterminal
      telopeptide (r = 0.46, P = 0.004), urinary pyridinoline (r = 0.61, P = 0.008),
      and urinary deoxypyridinoline (r = 0.61, P = 0.007). Levels of interleukin-6 also
      correlated with those of tumor necrosis factor-alpha (r = 0.44, P = 0.005).
      Multiple regression analysis indicated that interleukin-6, but not tumor necrosis
      factor-alpha, was independently predictive of bone resorption. We conclude that
      serum levels of interleukin-6 and tumor necrosis factor-alpha are increased in
      patients with primary hyperparathyroidism and are normalized by successful
      surgical treatment. The finding that these cytokines correlate with biochemical
      markers of bone resorption suggests that they play a role in the pathogenesis of
      bone loss in primary hyperparathyroidism.

PMID- 8855785
TI  - Delayed puberty.

PMID- 8855786
TI  - Severe insulin resistance, diabetes mellitus, hypertriglyceridemia, and
      pseudoacromegaly.

PMID- 8855787
TI  - Effects of testosterone replacement on muscle mass and muscle protein synthesis
      in hypogonadal men--a clinical research center study.
AB  - Testosterone replacement in hypogonadism has long been known to promote nitrogen
      retention and increase body density, but the mechanisms of nitrogen retention and
      body composition changes are poorly defined. We measured body composition and
      muscle protein synthesis in five hypogonadal men before and 6 months after
      initiating testosterone replacement. Body composition was examined using dual
      energy X-ray absorptiometry. Muscle mass was estimated both by excretion of
      creatinine on a meat-free diet and from appendicular mass measured using dual
      energy X-ray absorptiometry. Muscle protein synthesis was assessed by measuring
      the increment of [13C]leucine in mixed muscle protein and myosin heavy chain
      during a continuous infusion of L-[l-13C]leucine. In all subjects there was an
      increase in fat-free mass (average, 15%; range, 10-22%; P = 0.02) and a decrease
      in fat mass (-11%; range, -0.4% to -22.0%; P = 0.03). Muscle mass also increased
      in everybody (mean, 20%; range, 11-32%; P = 0.04) such that 65% of the increase
      in fat-free mass could be attributed to accretion of muscle. The accumulation of
      muscle was associated with a 56% (P = 0.015) increase in the fractional synthesis
      rate of mixed skeletal muscle proteins and a trend toward a similar increase in
      the fractional synthesis rate of myosin heavy chain (46%; P = 0.098). We conclude
      that testosterone replacement in hypogonadal men enhanced skeletal muscle mass by
      stimulating the muscle protein synthesis rate.

PMID- 8855788
TI  - Transfer and metabolism of thyrotropin releasing hormone across the perfused
      human term placenta.
AB  - The transport and uptake of TRH was investigated in the maternal-fetal-placental
      unit of perfused human term placenta. The degradation of TRH in biological fluid
      was first determined by incubating [125I]TRH with 100 microL 50% maternal or cord
      sera with or without pretreatment with 200 microM of p-hydroxymercuriphenyl
      sulfonic acid (p-HMSA), a proline dipeptidase inhibitor. Transplacental transfer
      of TRH was then studied by adding 10 microCi of [125I]- or [3H]TRH to the
      maternal circulation of dually perfused isolated lobule of human term placenta
      with or without 200 microM p-HMSA. Creatinine was used as an internal marker. The
      rate of degradation of TRH (P < 0.001) and inhibition by p-HMSA were
      significantly higher in maternal than cord sera (P < 0.05). In the maternal
      circulation, TRH concentration declined rapidly from 100% at time 0 to 33.5 +/-
      1.2% at 120 min. The fetal concentration increased from undetectable levels to a
      maximum of 1.8 +/- 0.3% at 120 min with a low feto-maternal ratio (0.08 +/-
      0.02). Perfusion in the presence of p-HMSA, however, did not significantly change
      fetal concentration, or the maternal and fetal concentration-time integral levels
      of TRH. Chromatography of maternal, fetal, and placental homogenates showed that
      TRH was metabolized by the placenta into small molecular weight fragments
      predominantly released in the maternal circulation. These results suggest that
      human placenta acts as an enzymatic barrier to the free passage of TRH.

PMID- 8855789
TI  - Analysis of the thyrotropin receptor as a candidate gene in familial Graves'
      disease.
AB  - Familial clustering of Graves' disease indicates a genetic etiology. Searches for
      genetic factors additional to the known human leukocyte antigen (HLA) association
      have implicated the gene for the TSH receptor (TSHR). We analyzed the linkage and
      association among three recently described microsatellite markers within the TSHR
      introns in Graves' disease in large multiply affected Welsh and English families
      (223 members, 44 affected individuals). Linkage analysis under a dominant model
      strongly rejected the hypothesis that TSHR is linked to Graves' disease in these
      families (lod score = -4.53). More detailed analyses also failed to provide
      evidence for linkage; these included combined segregation and linkage analysis,
      correction for HLA-DR3 status, allowance for the levels of thyroid autoantibodies
      in unaffected pedigree members, consideration of a recessive model for the
      disease, and linkage disequilibrium between disease and marker alleles. We also
      considered the possibility of a genetic heterogeneity of Graves' disease and thus
      analyzed separately the different families with a similar result. Although these
      results cannot eliminate a minor role of the TSHR gene locus in the genetics of
      Graves' disease, they argue against it being a major genetic determinant in this
      pathology.

PMID- 8855790
TI  - Longitudinal changes in bone mineral density and bone turnover in postmenopausal
      women with primary hyperparathyroidism.
AB  - The aims of this study were to determine 1) whether primary hyperparathyroidism
      (PHPT) is associated with accelerated bone loss in postmenopausal women, 2)
      whether bone mineral density (BMD) and bone turnover change to a similar extent
      with surgery and hormone replacement therapy (HRT) in these patients, and 3)
      whether biochemical markers of bone turnover measured at baseline can be used to
      predict the change in BMD in these patients after different therapies. We studied
      33 postmenopausal women with PHPT; their ages at the time of study ranged from 48
      80 yr (mean +/- SD, 63 +/- 10). Total body (TB), lumbar spine (LS), and femoral
      neck (FN) BMD and biochemical markers of bone turnover were measured at baseline
      and 10-30 months (19 +/- 5) after parathyroid surgery, HRT, or no treatment. BMD
      was measured in 33 age-matched healthy controls at baseline and at a mean of 24
      months. Baseline biochemical markers of bone turnover were measured in controls.
      In PHPT at baseline, the mean z-score of BMD was -1.25 at TB (95% confidence
      interval, -1.64 to -0.86), -0.95 at LS (-1.37 to -0.53), and -1.30 at FN (-1.65
      to -0.95), whereas the mean z score was 0.45 for serum carboxy-terminal
      propeptide of human type I procollagen (0.02-0.89), 1.05 for bone alkaline
      phosphatase (0.38-1.71), 2.38 for 24-h urinary excretion of cross-linked N
      terminal telopeptide of type I collagen (NTx; 1.63-3.13), and 2.36 for 24-h
      urinary excretion of galactosyl hydroxylysine (1.97-2.74). After surgery and HRT,
      BMD increased and bone turnover decreased during the follow-up. In the untreated
      group, BMD decreased at TB and FN, and levels of bone alkaline phosphatase,
      NTx/creatinine, and galactosyl hydroxylysine/creatinine increased. When the rate
      of change in BMD (percentage per yr) was compared with that in the control group,
      bone gain was significant at all three skeletal sites after surgery and HRT, and
      bone loss was significant at TB and FN, but not at LS, in the untreated group.
      There was a weak, but significant, correlation between baseline urinary NTx and
      the change in femoral neck BMD in the untreated group (r = -0.36; P = 0.05). We
      conclude that untreated postmenopausal women with PHPT have low BMD resulting
      from accelerated bone loss at the TB and FN. Surgery and HRT both restore BMD and
      bone turnover toward normal in postmenopausal women with PHPT. A single
      measurement of bone turnover is insufficient to predict BMD changes in individual
      patients with PHPT.

PMID- 8855791
TI  - Acute effect of brief low- and high-intensity exercise on circulating insulin
      like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in
      young healthy men.
AB  - We measured circulating levels of the GH insulin-like growth factor (IGF) system
      in response to brief exercise of different intensities. Ten males (mean age 28 +/
      5 yr) were studied on three separate occasions: once under resting conditions
      (control) and once each performing 10 min of low- or high-intensity exercise.
      Blood samples were assayed by RIA for GH, IGF-I and -II, IGF-binding protein-3
      (IGFBP-3), and IGFBP-3 proteolytic activity. After 10 min of low-intensity
      exercise, IGF-I and IGFBP-3 had increased over preexercise baseline by 7.7 +/-
      2.7% (P < 0.05) and 12.5 +/- 3.3% (P < 0.004), respectively. After 10 min of high
      intensity exercise, all measured components of the IGF system were increased: IGF
      I by 13.3 +/- 3.2% (P < 0.002), IGF-II by 15.7 +/- 3.1 (P < 0.01), and IGFBP-3 by
      23 +/- 6% (P < 0.001). IGFBP-3 proteolytic activity also was increased (44 +/-
      14% above baseline, P < 0.05). GH reached its peak 10 min after the cessation of
      high-intensity exercise, unlike the earlier peaks of IGF-I and II. In summary: 1)
      brief exercise leads to small but significant increases in circulating IGF-I, IGF
      II, IGFBP-3, and IGFBP-3 proteolysis; and 2) these responses may be influenced by
      exercise intensity. The IGF responses seem to be unrelated to GH. Acute exercise
      induced proteolysis of IGFBP-3 may contribute to anabolic effects of physical
      activity by increasing the bioavailability of IGF-I.

PMID- 8855792
TI  - Immunocytochemical detection of p53 in human thyroid carcinomas is associated
      with mutation and immortalization of cell lines.
AB  - Mutations in the tumor suppressor gene p53 are the most-common mutations found in
      human cancers. In thyroid cancers, p53 mutations generally are found only in
      poorly differentiated and undifferentiated tumors and in cell lines. To determine
      the prevalence of p53 mutations in thyroid neoplasms and thyroid cell lines, we
      screened 58 thyroid tissues and 3 thyroid cell lines, p53 primers bracketing
      exons 4, 5/6, 7, and 8 were used to amplify genomic DNA using the PCR. Mutations
      were screened by denaturing gradient gel electrophoresis and confirmed by
      sequencing. The two papillary thyroid cancer cell lines and the follicular
      thyroid carcinoma cell line (positive control) had transitions (CGT->CAT) in exon
      8, codon 273, resulting in the replacement of arginine with histidine. No normal
      thyroid tissues or primary tumors from which the cell lines were derived
      demonstrated exon 8 mutations, using this technique. p53 immunocytochemistry
      demonstrated a progression of p53 immunopositivity between synchronous and
      metachronous neoplasms, paralleling the neoplastic progression from a benign
      adenoma to primary carcinoma, regional, and distant metastasis and ultimately,
      the cell lines, where intense immunopositivity is noted. In addition,
      fluorescence in situ hybridization, using probes specific for the p53 locus,
      revealed the presence of 3 homologues of p53 in the follicular cell line and 2
      homologues in the papillary and Hurthle cell lines. These results suggest that a
      point mutation present in a small number of original tumor cells and
      amplification of the mutant allele may be responsible for immortalizing well
      differentiated thyroid cancer cells into cell lines.

PMID- 8855793
TI  - Selective recognition of M235T angiotensinogen variants and their determination
      in human plasma by monoclonal antibody-based immunoanalysis.
AB  - The common M235T mutation of human angiotensinogen has been shown to be
      associated with a 10-20% increase in plasma angiotensinOgen level and increased
      frequency of essential and pregnancy-induced hypertension. The detection of such
      a common factor in the plasma of individuals at risk could be a useful tool for
      modern molecular-based medicine. The recognition of M235T variants was
      investigated using four monoclonal antibodies (mAbs) directed against human
      angiotensinogen; two immunometric assays were developed. The first assay (using
      mAbS 7B2 and 4G3) allowed the direct determination of angiotensinogen
      concentrations and did not show a significant difference with the enzymatic
      measurement of angiotensinogen. The second assay (using mAbs 1H8 and 1C11) showed
      a fine distinction between the T235 mutant and M235 wild-type forms of
      angiotensinogen, with a greater affinity for the latter, as confirmed by
      biosensor BIAcore experiments. This assay was extremely sensitive in measuring
      the proportions of the M235 and T235 forms present in the test samples, the first
      time such a distinction has been achieved in the serpin family. The simple
      immunoanalysis of the plasma allowed the direct determination of the M235T
      genotype of the individual tested. Furthermore, it was shown that the T174M
      mutation, described as being in complete linkage disequilibrium with the M235T
      mutation, had no influence on these results. Moreover, this assay suggested the
      presence of the M235 and T235 angiotensinogens in approximately equal amounts in
      heterozygous plasmas. In conclusion, the immunometric assay described in this
      study should provide original tools for investigating the relationship between
      M235T genotype, plasma angiotensinogen levels, and regulation of blood pressure.

PMID- 8855794
TI  - Normalization of insulin sensitivity and glucose homeostasis in type I diabetic
      pancreas transplant recipients: a 48-month cross-sectional study--a clinical
      research center study.
AB  - Despite the establishment of heterotopic, whole cadaveric, pancreas-kidney
      transplantation as an effective form of therapy for type I diabetes with chronic
      renal insufficiency, uncertainty remains regarding the potentially deleterious
      effects of severe peripheral hyperinsulinemia and long-term immunosuppressive
      therapy on insulin sensitivity (SI) and, subsequently, on beta-cell function and
      maintenance of euglycemia over years. To examine the alterations in SI that may
      occur over time and their impact on glucose homeostasis, beta-cell function, SI,
      and glucose effectiveness (SG) were measured using the frequently sampled iv
      glucose tolerance test (FSIGTT) and minimal model method in 39 glucose-tolerant
      type I diabetic pancreas-kidney transplant recipients in a cross-sectional manner
      at 3, 6, 12, 24, 36, and 48 months post transplantation. Mean basal and
      poststimulation (oral glucose tolerance test and FSIGTT) serum glucose responses
      were similar among the groups from 3-48 months. Plasma insulin response during
      the FSIGTT was higher (P < 0.001, repeated measures ANOVA) at 6 months vs. 12-48
      months. Incremental integrated areas under the curve for 1st phase, glucose
      stimulated, tolbutamide-stimulated, and total insulin responses tended to be
      higher (P = NS) at 6 months. Glucose disappearance rate constant, kG, did not
      differ significantly from 3-48 months. Mean +/- SE S1 in the pancreas-kidney
      recipients was 4.25 +/- 1.6 x 10(-4) min-1/microU.mL-1 at 3 months (group 1, n =
      7) (vs. 7.9 +/- 0.9 x 10(-4) normal reference), decreased to 2.95 +/- 0.6 at 6
      months (group 2, n = 11), improved to baseline values of 4.6 +/- 1.0 at 12 months
      (group 3, n = 10), and normalized at 24 months (group 4, n = 6) to 7.5 +/- 1.7 (P
      = 0.008). The normalisation in SI was sustained at 36 months (group 5, n = 3, 8.0
      +/- 3.7, P = 0.03), and up to 48 months (group 6, n = 5, 6.1 +/- 1.6, P = 0.04)
      in the type I diabetic pancrease allograft recipients. Corresponding SG tended to
      increase but did not differ significantly from 3 (1.69 +/- 0.2 x 10(-2)/min), 6
      (2.33 +/- 0.39), 12 (1.9 +/- 0.2), 24 (1.9 +/- 0.4), 36 (1.98 +/- 0.15), and 48
      months (2.27 +/- 0.3). Hepatic insulin extraction did not differ among the
      groups. SI correlated significantly with prednisone dose (r = -0.45, P = 0.002).
      In summary, after successful whole cadaveric, heterotopic, pancreas-kidney
      transplantation in type I diabetic recipients: 1) euglycemia remains relatively
      stable over 48 months; 2) SI is diminished early after transplantation (3-6
      months), possibly caused by the effects of initially high doses of prednisone and
      hyperinsulinemia. However, this is compensated by a normal SG and by
      hyperinsulinemia to maintain euglycemia; 3) SI improves by 12 months and
      normalizes from 24-48 months, after transplantation, despite hyperinsulinemia and
      long-term immunosuppressive therapy. The time-dependent decrease in
      poststimulation insulin response after successful pancreas-kidney transplantation
      in type I diabetic recipients, therefore, is not caused by gradual beta-cell
      decline but rather is a response to normalization of SI. However, longitudinal
      studies pre-and post pancreas transplantation over an extended period of time
      will be necessary to confirm the present findings.

PMID- 8855795
TI  - Inhibin B secretion in males with gonadotropin-releasing hormone (GnRH)
      deficiency before and during long-term GnRH replacement: relationship to
      spontaneous puberty, testicular volume, and prior treatment--a clinical research
      center study.
AB  - To evaluate the physiology of inhibin B in the human male, we measured serum
      concentrations in normal adult men and men with isolated GnRH deficiency before
      and during long-term replacement with pulsatile GnRH. At baseline, inhibin B
      levels in the GnRH-deficient men (n = 31) were significantly lower than normal
      controls (85 +/- 10 pg/mL vs. 239 +/- 14 pg/mL; P < .01) and correlated
      positively with pretreatment testicular volume (r = .80, P = .001) and a history
      of spontaneous puberty, suggesting additional maturational influences on the both
      testicular volume and inhibin B secretion. Pulsatile GnRH administration was
      associated with significant increases in inhibin B, with levels averaging 108 +/-
      7 pg/mL when serum LH, FSH, and T concentrations had reached the normal adult
      male range (n = 22; P = .02 vs. baseline). Continued GnRH administration for at
      least an additional year was not associated with further increases in inhibin B
      concentrations. Throughout the course of long-term pulsatile GnRH replacement,
      serum FSH levels were negatively correlated with inhibin B concentrations (e.g. r
      = -.71, P < 0.01; n = 14 treated 12 months after normalization of T). Although
      inhibin B concentrations did not correlated with sperm density during therapy,
      rates of fertility were higher in patients with higher baseline levels (inhibin B
      > or = 60 pg/mL). Increases in serum concentrations of inhibin B occurring during
      GnRH replacement demonstrate the gonadotropin regulation of gonadal inhibin B
      secretion. However, the variation in baseline inhibin B levels before GnRH
      administration suggests an additional gonadotropin-independent level of
      modulation. The negative correlation between FSH and inhibin B secretion in GnRH
      deficient men receiving long-term GnRH replacement is consistent with a putative
      role of inhibin B in the negative feedback regulation of FSH, although direct
      confirmation of this role requires further investigation.

PMID- 8855796
TI  - Regulation and metabolic role of phospholipase D activity in human thyroid and
      cultured dog thyrocytes.
AB  - The actions of TSH, ATP, the ionophore A23187, the endoplasmic reticulum Ca(2+)
      ATPase inhibitor thapsigargin, and phorbol dibutyrate (PDBu) on 3H-cytidine
      monophosphate phosphatidic acid (3H-CMP-PA) accumulation were studied in human
      thyroid slices to evaluate PA generation and inositol recycling towards
      phosphatidyl-inositol synthesis. The effects of the same agonists also were
      measured on phosphatidylbutanol (PtdBut) generation in 3H-palmitate or 3H
      myristate prelabeled slices to assess the activity of phospholipase D (PLD). The
      phospholipid target of this PLD was determined on 3H-choline prelabeled human
      thyroid slices by measuring 3H-choline release in incubation medium and slices
      and 3H-choline incorporation in phospholipids. TSH (10 U/L) stimulated 3H-CMP-PA
      accumulation in an LiCl-and propranolol-insensitive way, as well as 2H-fatty
      acids incorporation into PA, diacylglycerol, and phosphatidylcholine (PtdCho)
      with on evidence of dose-dependent effects and had no detectable action on PLD
      activity. The effects of TSH were not reproduced by Bu2cAMP or forskolin.
      Thapsigargin and A23187 both increased CMP-PA accumulation and PtdBut generation,
      whereas ATP only stimulated PLD activity. The phorbol ester PDBu (5 x 10(-7)
      mol/L) increased PtdBut formation and 3-H-fatty acid incorporation into PtdCho,
      but had no effect on CMP-PA generation. Staurosporine (STSP) (5 x 10(-6) mol/L),
      a nonspecific inhibitor of protein kinase C, unexpectedly reproduced the effects
      of PDBu. The increase of 3H-choline in slices' supernatant and the decrease of 3H
      choline-labeled PtdCho induced by PDBu, ATP, thapsigargin, and STSP indicate that
      the activated PLD hydrolyzed PtdCho. We suggest that the PA generation induced by
      PLD stimulation could contribute to the stimulated H2O2 formation and iodide
      organification observed with the agonists inducing PtdBut accumulation. Indeed,
      Bu2cAMP and forskolin, known to decrease iodide organification in human thyroid,
      inhibited the PLD stimulation induced by ATP and PDBu. In cultured dog
      thyrocytes, phorbol esters, and STSP induced DNA synthesis and dedifferentiation,
      whereas thapsigargin inhibited TSH-induced growth and killed phorbol esters
      stimulated cells, suggesting a positive role of PLD stimulation towards
      dedifferentiated growth and of simultaneously raised [Ca2+)i and stimulated
      protein kinase C-PLD towards growth arrest and cellular death.

PMID- 8855797
TI  - A preliminary study of flutamide, testolactone, and reduced hydrocortisone dose
      in the treatment of congenital adrenal hyperplasia.
AB  - Treatment outcome in congenital adrenal hyperplasia is often suboptimal due to
      hyperandrogenism, treatment-induced hypercortisolism, or both. As a new approach,
      we hypothesized that the effects of androgen could be blocked by an antiandrogen
      (flutamide) and an inhibitor androgen to estrogen conversion (testolactone), thus
      allowing the hydrocortisone dose to be reduced. We conducted a short term pilot
      study in 12 children with congenital adrenal hyperplasia in a randomised cross
      over open design to determine whether flutamide, testolactone, reduced
      hydrocortisone dose, and fludrocortisone are more effective than hydrocortisone
      and fludrocortisone treatment in normalizing linear growth, weight gain, and bone
      maturation. Each regimen was administered for 6 months, with a 3-month washout
      period, consisting of hydrocortisone and fludrocortisone treatment, between
      regimens. Compared to hydrocortisone and fludrocortisone treatment, the regimen
      of flutamide, testolactone, reduced hydrocortisone dose (from 12.9 to 7.9 mg/m2
      day), and fludrocortisone produced an increase in plasma 17-hydroxyprogesterone
      levels (P < 0.05) and a decline in urinary cortisol (P < 0.01), linear growth
      rate (-0.9 +/- 0.5 vs. 1.4 +/- 0.6 SD U; P = 0.003), weight velocity (-0.80 +/-
      4.0 vs 0.6 +/- 0.4 SD U; P = 0.01), and bone maturation (0.6 +/- 0.6 vs. 1.4 +/-
      0.9 yr bone age/yr chronological age; P = 0.02). Although no important adverse
      effects were observed, the known potential for flutamide-induced hepatotoxicity
      made frequent monitoring essential. We conclude that the regimen of flutamide,
      testolactone, reduced hydrocortisone does, and fludrocortisone improve the short
      term control of growth and bone maturation in children with congenital adrenal
      hyperplasia. Long term studies are required to determine whether this approach
      can improve these children's growth and development.

PMID- 8855798
TI  - Gonadotropin-releasing hormone gene expression is increased in the medial basal
      hypothalamus of postmenopausal women.
AB  - Quantitative In situ hybridization and computer-assisted microscopy were used to
      compare GnRH gene expression in the hypothalamus of premenopausal and
      postmenopausal women. Hypothalamic sections were incubated with 35S-labeled 48
      base complementary DNA probes and dipped into nuclear emulsion for visualization
      of messenger ribonucleic acids at the single cell level. Two subtypes of GnRH
      neurons were examined: heavily labeled GnRH neurons located primarily in the
      medial basal hypothalamus (type I) and lightly labeled neurons in the dorsal
      preoptic-septal region (type II). We report a 50% increase in mean number of
      silver grains per type I neuron in the medial basal hypothalamus of
      postmenopausal women. In contrast to type I neurons, there was no difference in
      the number of grains per type II neuron in the dorsal preoptic-septal regions.
      The mean profile area and the number of type I GnRH neurons per section were not
      different between the two groups, and there was no change in the size of type II
      neurons. There was also a significant postmortem degradation of messenger
      ribonucleic acid in type I, but not type II, neurons. We hypothesize that the
      increase in GnRH gene expression in the medial basal hypothalamus of
      postmenopausal women is secondary to the ovarian failure of menopause and is not
      a nonspecific effect of age. The differential response of the two types of
      hypothalamic neurons provides additional evidence that distinct functional
      subgroups of GnRH neurons exist in the human brain.

PMID- 8855799
TI  - Establishment of anaplastic thyroid carcinoma cell lines useful for analysis of
      chemosensitivity and carcinogenesis.
AB  - Anaplastic thyroid carcinoma (ATC) is usually associated with a poor prognosis,
      with most patients dying within a few months. The mechanism of its carcinogenesis
      is unclear, and its rapid growth and spread often prevent effective surgical
      therapy. Thus, chemotherapy is necessary. However, ATC is often resistant to
      anticancer drugs. Therefore, prediction of chemosensitivity is important in
      selecting appropriate treatment. In this study, after the establishment of three
      cell lines (K119, KOA2, and IAA) from patients with ATC, we analyzed them for
      abnormalities in certain oncogenes (myc, ras, ret, and c-erbB2) and the p53 tumor
      suppressor gene. Only one of three cell lines (KOA2) had a N-ras mutation [codon
      61 CAA(Gln)-->CGA(Arg)] and a p53 gene mutation [exon 6 codon 192 Caa(Gln)-
      >TAG(stop)]. We also investigated their in vitro drug sensitivity and compared it
      with clinical chemosensitivity, retrospectively. In vitro drug sensitivity was
      determined using an adhesive tumor cell culture system. Only the K119 cells were
      sensitive to adriamycin and cisplatin in vitro. The other two were resistant to
      them in vitro. These results paralleled the clinical responses. We also evaluated
      the in vitro drug sensitivity of a poorly differentiated thyroid carcinoma cell
      line (SMP) and papillary thyroid carcinoma cell lines (NPA). None of the five
      cell lines expressed the multidrug resistance gene (mdr-1). In conclusion, we
      established ATC cell lines that are suitable models for characterizing the nature
      of multidrug resistance and carcinogenesis.

PMID- 8855800
TI  - Catecholamine content and in vitro catecholamine synthesis in peripheral human
      lymphocytes.
AB  - We studied the catecholamine (CA) content in peripheral human lymphocytes and the
      ability of these cells to synthesize CA in vitro. CA were separated by high
      performance liquid chromatography (HPLC) and determined in the supernatant by
      electrochemical detection as well as being determined after ultrasonic cell
      disruption in mononuclear leukocytes, adherent cells (monocytes/macrophages),
      total lymphocytes, and B- and T-cell enriched fractions. T lymphocytes contained
      L-Dopa and norepinephrine (NE), whereas B lymphocytes contained only L-Dopa.
      Lymphocytes seem to be able to synthesize NE from both L-tyrosine and L-Dopa
      added to the incubation medium in concentrations similar to the peripheral venous
      plasma (i.e. 5 x 10(-5) m and 10(-8) m, respectively). The addition of D-Dopa did
      not increase intracellular NE. alpha-methyl-p-L-tyrosine, benserazide,
      disulfiram, and fusaric acid (which are inhibitors of the enzymatic pathway) all
      decreased the synthesis of NE. After the addition of [3H]-L-Dopa (10(-8) m and
      10(-7) m) to the incubation medium, [3H]-NE and [3H]-dopamine appeared. By
      increasing the concentration of L-Dopa in the medium (< 10(-6) m), CA were
      detected in the supernatant as well. These data show that peripheral human T
      lymphocytes contain and are able to synthesize CA from normal precursors in
      physiologic concentrations, i.e. a CA synthetic pathway is shown in nonneural
      cells. These data seem to support the hypothesis of autocrine and paracrine loops
      in the regulation of lymphocyte activity in lymphocytes taken from human
      cerebrospinal fluid (as suggested by other authors).

PMID- 8855801
TI  - The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and
      dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from
      its low expression of 3 beta-hydroxysteroid dehydrogenase.
AB  - Based on indirect evidence, it has often been assumed that the zona reticularis
      of the adult human adrenal cortex is the source of the adrenal androgens,
      dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), but direct tests of this
      concept have been few. Using the techniques of cell culture, Northern blotting,
      and RIA, we compared the properties of separated adult zonal cells to those of
      fetal zone cells, a cell type well known to secrete large amounts of DHEA(S) due
      to its low expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). In
      nine glands from donors of a wide age range, the zona fasciculata and zona
      reticularis were separated and dissociated, and the cells were placed in culture.
      After 5 days, serum was removed by a 24-h period in serum-free defined medium
      followed by a 24-h exposure to cAMP analogs, with the optional addition of
      insulin, also in serum-free medium. The separated fasciculata and reticularis
      cells showed large differences in the DHEA(S)/cortisol (F) production ratios from
      added pregnenolone precursor, consistent with the synthesis of only F and
      essentially no DHEA(S) by fasciculata cells and with the synthesis of mostly
      DHEA(S) with little or no F by both reticularis cells and fetal zone cells. The
      different patterns of steroidogenesis were accompanied by a much lower level of
      expression of type II 3 beta HSD in reticularis cells, similar to that in fetal
      zone cells. In contrast, other genes were similarly regulated in the two adult
      zones and in the fetal zone by both cAMP and insulin. The levels of messenger
      ribonucleic acids for 17 alpha-hydroxylase, cholesterol side-chain cleavage
      enzyme, 21-hydroxylase, and 11 beta-hydroxylase responded to cAMP and insulin in
      both reticularis cells and fetal zone cells in the same pattern as that
      previously established in fasciculata cells. The central role of the limited
      expression of 3 beta HSD in the DHEA(S)-synthesizing property of reticularis
      cells was established by inhibition of 3 beta HSD in fasciculata cells with
      trilostane, which caused them to increase their DHEA/F production ratio to a
      level exceeding even that in fetal zone cells. There did not appear to any age
      related changes in gene expression that could account for the large age-related
      decline in DHEA(S) biosynthesis in humans in either reticularis or fasciculata
      cells. Thus, the most likely cause of the age-related decline in adrenal androgen
      biosynthesis is an age-related decline in the number of functional reticularis
      cells, without a major change in the differentiated properties of the zonal cells
      as a function of age.

PMID- 8855802
TI  - Pancreatic polypeptide administration improves abnormal glucose metabolism in
      patients with chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted
      nutrient-induced release of pancreatic polypeptide (PP). To investigate the
      possible role of PP on glucose metabolism, we studied male patients with
      documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic
      glucose production (HGP) and overall glucose disposal rates were determined by [3
      3H]glucose infusion during a hyperinsulinemic-euglycemic clamp during three
      separate admissions. Basal rates of HGP were higher in CP patients. In response
      to an infusion of insulin (60 pmol.m-2.min-1), HGP fell 91 +/- 5% in NL subjects
      but only 68 +/- 8% in CP subjects (P < 0.05). One month later, the clamp was
      repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol.kg-1.min
      1). HGP before the insulin infusion and its subsequent suppression (NL: 83 +/-
      5%; CP: 86 +/- 15%) were nearly identical between groups. In follow-up studies 1
      month after the PP infusion, HGP both basally and in response to insulin alone
      were similar to the first study. During oral glucose tolerance tests (OGTT)
      performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT
      responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic
      (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels
      (approximately -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month
      after the PP treatment showed a return to pretreatment responses. We conclude
      that chronic pancreatitis accompanied by PP deficiency is associated with partial
      hepatic resistance both in the basal state and in response to hyperinsulinemia.
      This impairment is reversed after iv PP administration. PP deficiency may
      therefore play a role in the development of pancreatogenic diabetes caused by
      pancreatic injury.

PMID- 8855803
TI  - Factitious Cushing syndrome.
AB  - There have been few reports of factitious Cushing syndrome. To characterize the
      clinical and laboratory features leading to this unusual diagnosis, we describe 6
      patients (5 women, 1 man), ages 31-44, identified retrospectively among 860
      patients evaluated for hypercortisolism at the National Institutes of Health
      Clinical Center. All six patients had multiple surgeries unrelated to Cushing
      syndrome and a history of depression or anxiety. Four patients had close contact
      with the medical profession, three a history of drug abuse, and three had
      undergone previous treatment for Cushing syndrome. The physical features of
      Cushing syndrome were variable and not helpful in the differential diagnosis with
      endogenous Cushing syndrome. Four patients had striking variability in urine-free
      cortisol (UFC) and 17-hydroxysteroid (17-OHCS) values from low to high. Adrenal
      computed tomography, performed in two patients, showed small adrenal glands (n =
      1) or a left-sided mass (n = 1), and adrenal magnetic resonance imaging,
      performed in one patient, showed atrophic glands. Pituitary magnetic resonance
      imaging, carried out in four patients, was either normal (n = 1) or exhibited
      questionable signs of microadenoma (n = 3). Determination of synthetic
      glucocorticoids by high pressure liquid chromatography (HPLC) was positive in the
      four patients in whom it was performed. Factitious Cushing syndrome is a
      difficult diagnosis. To conserve time and resources, high pressure liquid
      chromatography analysis of urine steroids, the most definitive test for the
      factitious disorder, should be performed whenever there is clinical suspicion of
      glucocorticoid abuse.

PMID- 8855804
TI  - Testosterone replacement therapy improves mood in hypogonadal men--a clinical
      research center study.
AB  - The effect of testosterone (T) replacement on changes in mood was studied for 60
      days in 51 hypogonadal men. All patients were withdrawn from their prior T
      replacement for at least 6 weeks before enrollment. Of these patients, 18
      received T enanthate 200 mg im every 20 days, 16 received sublingual T
      cyclodextrin (SLT) at a dose of 2.5 mg three times daily, and 17 received SLT at
      a dose of 5.0 mg three times daily. The total treatment period was 60 days. The
      patients were asked to respond to a questionnaire on 7 consecutive days before
      the start of treatment and on 7 consecutive days before their visits to the
      clinic on days 21, 41, and 60 of treatment. The following mood parameters were
      assessed using a 7-point Likert rating scale: angry, alert, irritable, full of
      pep (energy), sad/blue, tired, friendly, nervous, and well/good. When compared
      with the baseline period, T replacement led to significant decreases in anger (P
      = 0.0045), irritability (P = 0.0009), sadness (P = 0.0033), tiredness (P =
      0.0035), and nervousness (P = 0.0291), and significant improvement in energy
      level (P = 0.0020), friendliness (P = 0.0072), and sense of well-being (P =
      0.024) in all subjects as a group. Analyses of the area under the curve (AUC) of
      baseline serum T levels before T replacement showed significant positive
      correlations between serum T (AUC) and friendliness (r = 0.29, P < 0.05) and
      sense of well-being (r = 0.27, P < 0.05), and significant negative correlations
      with nervousness (r = -0.27, P < 0.05), irritability (r = -0.29, P < 0.05) and
      tiredness (r = -0.28, P < 0.05). Similar correlations were found between serum
      dihydrotestosterone (DHT) and some of the mood parameters. After T replacement in
      the hypogonadal men, these correlations between AUC of serum T levels and the
      positive and negative mood scores disappeared. These results were corroborated in
      a subsequent study in which 30 hypogonadal men were supplemented with SLT 5 mg
      three times daily for 6 months. The patients were less nervous (P = 0.0025) and
      more alert (P = 0.0004), friendly (P = 0.042), and energetic (P = 0.0001) during
      the 6-month treatment period compared with baseline. We conclude that T
      replacement therapy in hypogonadal men improved their positive mood parameters,
      such as energy, well/good feelings, and friendliness and decreased negative mood
      parameters including anger, nervousness, and irritability, and direct
      correlations between serum T and DHT with mood scores were only observed in the
      baseline period when serum androgen levels were below the normal range. The
      latter observation suggests that once a minimally adequate serum T/DHT level was
      achieved by T replacement therapy, further increases in serum T/DHT levels did
      not further contribute to the improvement in mood variables.

PMID- 8855805
TI  - Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH
      related peptide receptor: comparison with primary hyperparathyroidism.
AB  - In Jansen's disease (JD), the hypercalcemia found in about half the cases is the
      result of a mutant, constitutively overactive, form of the PTH/PTHrP receptor,
      which in these cases also causes the skeletal dysplasia. The subject of the
      present report was first seen in 1956 and is still under treatment at the same
      medical center. We report the clinical course and a detailed study of calcium and
      bone metabolism carried out in 1976 and compare the results with those of six
      typical patients with mild primary hyperparathyroidism in whom exactly the same
      studies were carried out. In the patient with JD, the hypercalcemia was of early
      onset; chronic and nonprogressive; refractory to the administration of phosphate,
      glucocorticoid, and calcitonin; and accompanied by suppressed PTH levels as
      determined by two different immunoassays, an undetectable PTHrP level, increased
      excretion of nephrogenous cAMP (an in vivo bioassay of endogenous PTH
      production), decreased tubular reabsorption of phosphate, increased tubular
      reabsorption of calcium, increased biochemical indexes of bone turnover, and
      increased histological indexes of bone turnover on iliac bone histomorphometry
      after double tetracycline labeling. There was exaggerated loss of cortical bone
      and preservation of cancellous bone. All the results in JD relating to renal or
      skeletal effects of PTH excess were within or close to the ranges found in the
      hyperparathyroid patients, except that tubular reabsorption of phosphate was more
      depressed. Because PTH secretion was suppressed, any effects mediated by putative
      alternative receptors would have been diminished. We conclude that 1) the
      hypercalcemia due to constitutive overactivity of the PTH/PTHrP receptor is
      indistinguishable from that of mild primary hyperparathyroidism in clinical
      characteristics and renal tubular and skeletal features; and 2) the classic
      laboratory manifestations of primary hyperparathyroidism, with the possible
      exception of osteitis fibrosa cystica, can all be accounted for by overactivity
      of a single receptor.

PMID- 8855806
TI  - Urinary pyridinium collagen cross-links predict growth performance in children
      with idiopathic short stature and with growth hormone (GH) deficiency treated
      with GH. Skeletal metabolism during GH treatment.
AB  - GH is able to promote longitudinal growth in children with GH-deficiency (GHD)
      and in some children with idiopathic short stature (ISS). The objectives of this
      study were to evaluate the predictive value of bone and collagen markers on the
      growth response to GH therapy in children with ISS and with GHD, and to
      characterize the effects of GH treatment on bone and collagen turnover in
      children with ISS and with GHD. Twenty prepubertal short, slowly growing,
      children treated with GH, 15 IU/m2 per week, were studied; of them 13 (10 males)
      had ISS and 7 (5 males) had GHD. An overnight 12-h urinary collection and a
      fasting morning blood sample were obtained at baseline, 1, 3, 6, and 12 months of
      treatment. Urinary levels of collagen cross-links, pyridinoline (Pyd) and
      deoxypyridinoline (Dpd), and circulating levels of osteocalcin, intact PTH,
      calcitonin, procollagen type III aminoterminal propeptide (PIIINP), insulin-like
      growth factor-I, and alkaline phosphatase were determined. Urinary collection was
      also obtained from 127 healthy children (51 males) aged 6-13 yr. In children with
      ISS, the changes in Dpd over 1 month of GH therapy were related to the changes in
      height velocity (HV) over 1 yr of therapy (r = 0.67; P < 0.05); the changes in
      Pyd after 1 month of GH treatment were related to the changes in HV at 6 months
      of GH treatment (r = 0.57; P < 0.05). All the other markers evaluated were not
      related to the HV changes in children with ISS. In children with GHD, the changes
      in Pyd and in Dpd after 1 month of GH treatment were positively related to the
      changes in HV after 12 months of therapy (r = 0.82; P < 0.05, and r = 0.82; P <
      0.05, respectively). The changes in Pyd after 1 month were also related to the HV
      changes after 6 months of GH (r = 0.77; P < 0.05). Positive relationships between
      the HV after 6 months of GH and the increases of PIIINP (r = 0.80; P < 0.05) and
      osteocalcin (r = 0.77; P < 0.05) after 3 months of GH therapy were observed. All
      patients showed urinary Dpd and Pyd excretions in the normal range. In patients
      with ISS, Pyd (P < 0.05), Dpd (P < 0.05), osteocalcin (P < 0.01), PIIINP (P <
      0.01), and alkaline phosphatase (P < 0.01) increased longitudinally during the GH
      treatment and the increments reached a maximum after 3-6 months of therapy.
      Patients with GHD showed an increase of the same markers but the increases
      occurred earlier, after 1 month of GH therapy. The collagen cross-links, Pyd and
      Dpd, could be helpful early markers in predicting the responsiveness to GH
      therapy in children with ISS and with GHD. GH treatment stimulates bone and
      collagen metabolism.

PMID- 8855807
TI  - Human ovarian expression of 17 beta-hydroxysteroid dehydrogenase types 1, 2, and
      3.
AB  - Three isozymes of 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) have been
      cloned and characterized as distinct gene products (17 beta HSD1, 17 beta HSD2,
      and 17 beta HSD3). The presence and location of these isozymes in the human ovary
      have not been defined. In this study, we utilized Northern analysis and RT-PCR to
      examine transcripts for the three isozymes of 17 beta HSD. RNA was isolated from
      ovarian cortex, stroma (pre- and postmenopausal), hilum, follicles, and corpora
      lutea obtained from adult women, as well as whole fetal ovaries. By Northern
      analysis, high levels of 17 beta HSD1 messenger RNA were found in follicles,
      corpora lutea, and cortex, whereas low levels were detected in the postmenopausal
      stroma and in fetal ovaries by RT-PCR. 17 beta HSD1 messenger RNA was not
      detected in hilar tissue by either Northern analysis or RT-PCR. Utilizing RT-PCR,
      transcripts for 17 beta HSD2 were not detectable in cortex, stroma, (pre-or
      postmenopausal), hilum, or follicles, but were present in RNA derived from the
      corpora lutea and fetal ovary. The androgenic isozyme 17 beta HSD3 was not
      detectable in any of the ovarian compartments examined by either Northern
      analysis or RT-PCR. These data provide additional insight into the mechanism of
      testosterone and estradiol synthesis within the ovary. Specifically, the high
      level of 17 beta HSD1 is clearly localized to follicles and corpora lutea
      indicating involvement in the synthesis of estradiol. Secondly, androgenic 17
      beta HSD3 is not expressed in the human ovary. Thus testosterone production
      within the human ovary, occurring under physiological conditions, arises from
      either the 17 beta HSD1 or an uncharacterized isozyme.

PMID- 8855808
TI  - Cyclic changes in lipoprotein and apolipoprotein levels during the menstrual
      cycle in healthy premenopausal women on a controlled diet.
AB  - Lipoprotein, apolipoprotein (apo), and hormone levels were measured in 12 healthy
      women over three consecutive menstrual cycles, one free-living and two under
      controlled dietary conditions. Serum hormone levels were measured to identify
      menstrual cycle phases (menses, early follicular, late follicular, and
      midluteal). After stabilization for one cycle on the controlled diet, ANOVA
      modeling of the second controlled-diet cycle revealed that low-density
      lipoprotein (LDL) cholesterol levels in the midluteal phase were significantly
      lower (by 7%) than in the early follicular phase. High-density lipoprotein (HDL)
      cholesterol levels during the late follicular phase were higher (by 6%) than
      menses levels. Differences in the HDL-cholesterol and apoA-I fluctuations
      resulted in a higher proportion of HDL-cholesterol to apoA-I during the late
      follicular phase than that during the menses phase. The ratios of LDL
      cholesterol/HDL cholesterol and apoB/apoA-I in the early follicular phase were
      greater by 5.6% and 6.0%, respectively, than those in the midluteal phase.
      Fluctuations in total cholesterol, triglyceride, apoA-I, and apoB did not reach
      significance. Thus, the cyclic fluctuations of LDL and HDL cholesterol need to be
      considered in the screening and medical monitoring of women with borderline
      lipoprotein levels, as well as in the design and the interpretation of results of
      studies involving premenopausal women.

PMID- 8855809
TI  - Hypercortisolemia increases plasma interleukin-10 concentrations during human
      endotoxemia--a clinical research center study.
AB  - Hypercortisolemia directly before the administration of endotoxin (LPS) to normal
      humans completely prevents the release of the proinflammatory cytokine tumor
      necrosis factor, whereas hypercortisolemia 12 h to 7 days before the injection of
      LPS is associated with enhanced tumor necrosis factor release. To determine the
      effect of elevated cortisol levels on the secretion of the antiinflammatory
      cytokine interleukin-10 (IL-10), 23 healthy men were given iv LPS (lot EC-5; 2
      ng/kg) alone or in combination with a continuous iv infusion of hydrocortisone (3
      micrograms/kg.min) for 6 h immediately before or 6, 12, or 144 h before LPS
      injection. LPS induced a monophasic increase in plasma IL-10 concentrations that
      peaked after 2 h (162 +/- 27 pg/mL; P < 0.0001). In subjects who were infused
      with hydrocortisone directly before LPS administration, IL-10 concentrations were
      much higher (1784 +/- 331 pg/mL; P < 0.0001 vs. LPS only), whereas
      hypercortisolemia 6, 12, or 144 h before LPS injection did not influence LPS
      induced IL-10 levels. In human whole blood in vitro, hydrocortisone caused a dose
      dependent reduction of LPS-induced IL-10 levels. Further, hydrocortisone reversed
      the increase in IL-10 concentrations by epinephrine in LPS-stimulated whole
      blood. Stimulation of IL-10 release may contribute to the antiinflammatory
      properties of glucocorticoids.

PMID- 8855810
TI  - Cytogenetic and microsatellite alterations in tumors from patients with the
      syndrome of myxomas, spotty skin pigmentation, and endocrine overactivity (Carney
      complex).
AB  - Carney complex (CC) is a familial multiple neoplasia and lentiginosis syndrome,
      transmitted in an autosomal dominant manner. It is the only familial form of
      cardiac and skin myxomas known and includes endocrine neoplasms causing Cushing's
      syndrome [primary pigmented nodular adrenocortical disease (PPNAD)] and
      acromegaly (GH-producing adenoma). The molecular defect leading to CC remains
      unknown, but was recently mapped to chromosome 2p16 by linkage analysis. This
      region has exhibited cytogenetic aberrations in atrial myxomas from patients with
      CC and harbors the hMSH2 and hMSH6 genes, which are involved in the preservation
      of microsatellite length stability of replicating human cells. In the present
      study, we examined 15 tumor and normal tissue specimens from 13 patients with CC
      [GH-producing adenoma (n = 1), adrenal tumors (PPNAD, n = 8), thyroid cancer (n =
      1), normal adrenal gland (n = 1)] and 4 cultured cell lines [heart myxoma (n = 3)
      and eyelid myxoma (n = 1)]. Chromosome analysis was obtained by standard
      cytogenetic techniques. One of the myxoma cell lines and 3 PPNAD specimens
      contained multiple telomeric associations (tas). The normal adrenocortical tissue
      from a patient with PPNAD contained no apparent chromosomal anomalies, whereas
      the neighboring PPNAD tissue demonstrated tas. DNA was extracted from peripheral
      blood, tumor cell lines, and frozen or paraffin-embedded tissues and subjected to
      PCR amplification with primers from 64 microsatellite locations covering
      chromosomes 1 and 3-22 and 14 loci covering chromosome 2. The alterations
      detected were loss and gain of heterozygosity (LOH and GOH; 49% and 26%,
      respectively), deletions of both alleles (DEL; 10%), and microsatellite length
      instability (15%). GOH and LOH were the most frequent changes, with telomeric
      markers significantly over-represented (P < 0.05). Chromosomes 6, 11, 22, 10, and
      19 demonstrated mostly LOH, GOH, or DEL in over 40% of the informative loci
      tested (73%, 59%, 47%, 46%, and 44%, respectively), whereas markers on chromosome
      2 showed only microsatellite length instability (10%). The degree of genomic
      instability and its type were independent of tumor type (P > 0.1). We conclude
      that tumors and tumor cell lines from patients with CC demonstrate significant
      genomic, but not microsatellite length, instability. Thus, the CC gene(s) on
      chromosome 2p16 is different from the hMSH2 and hMSH6 genes and has dominant,
      rather than recessive, tumorigenic function. This gene(s) appears to be involved
      in the regulation of genomic stability of dividing cells, in particular the
      structure of telomeres in replicating chromosomes and/or the function of the
      mitotic apparatus.

PMID- 8855811
TI  - A randomized, controlled trial of estradiol replacement therapy in women with
      hypergonadotropic amenorrhea.
AB  - Premature ovarian failure is classically defined as menopause occurring before
      age 40 and is associated with elevated serum FSH levels. If elevated FSH levels
      indicate lack of ovarian feedback and depletion of primordial follicles, women
      with prematurely elevated FSH levels should have infertility. However, there are
      many reports of pregnancies in affected women occurring during estrogen therapy
      leading to the hypothesis that estrogen may have a salutary effect on
      folliculogenesis and conception. This randomized, controlled trial was designed
      to investigate whether estrogen replacement therapy offered a significant
      therapeutic benefit in hypergonadotropic amenorrhea and to evaluate the potential
      pathophysiologic mechanisms that would explain the reported pregnancies. Thirty
      seven women, aged 16 to 40, with menstrual dysfunction and documented FSH levels
      elevated above the 95% confidence limits of the mid-cycle gonadotropin peak of
      the normal menstrual cycle (> 40 IU/L 2nd IRP hMG in our RIA) on at least two
      occasions, entered the study. The average duration of their amenorrhea was 15.9
      months (range 2-96 months). Subjects were randomized to begin estradiol
      replacement (micronized estradiol [Estrace TM], 2 mg orally each day) or no
      therapy for 6 weeks in a 12-week, cross-over design with weekly monitoring by
      both pelvic ultrasonography and serum hormone levels. Thirty-one women completed
      the entire randomized study. As expected, estradiol therapy increased mean serum
      estradiol levels by 98 pg/mL and was associated with a significant decrease in
      mean LH and FSH levels (LH: 45.4 IU/L 2nd IRP hMG vs. 37.1 IU/L, FSH: 63.4 IU/L
      vs. 40.6 IU/L, geometric means). However, there was no effect of estradiol
      replacement on mean ovarian volume, the number or size of new follicles, or the
      ovulation rate in all subjects or in the subset with no identified cause for
      their hypergonadotropic hypogonadism (n = 20). Two pregnancies occurred during
      the randomized trial, one on and one off estradiol. In both arms of the study,
      the majority of subjects developed cystic ovarian structures by ultrasound that
      were temporally associated with increasing serum estradiol levels, indicating
      functional ovarian follicles. Seventy-eight percent of all subjects grew at least
      one new follicle over 10 mm in diameter and 46% ovulated at least once, as
      determined by a serum progesterone level more than 4 ng/mL. Although ovulations
      were significantly more common in the 10 women subjects who had less than 3
      months of amenorrhea (all of whom ovulated) than in the 27 with greater than 3
      months of amenorrhea (only 7 of whom ovulated (26%), P < 0.001), there was no
      significant difference in eventual pregnancies (2 of the 10 women with less than
      3 months of amenorrhea vs. 3 of the 27 with greater than 3 months of amenorrhea,
      P = 0.47). We conclude that in hypergonadotropic women with amenorrhea: 1)
      folliculogenesis occurs often but is less frequently followed by ovulation and
      rarely by pregnancy, suggesting that elevated FSH is a marker of oocyte
      dysfunction occurring distinct from and earlier than granulosa cell or follicular
      dysfunction; and 2) estrogen therapy does not improve the rate of
      folliculogenesis or ovulation.

PMID- 8855812
TI  - In vivo and in vitro evidence for iodide regulation of major histocompatibility
      complex class I and class II expression in Graves' disease.
AB  - Increases in thyroid cell major histocompatibility complex (MHC) class I and
      class II expression have been suggested to be an important factor in the
      development or perpetuation of Graves' disease. It is hypothesized that
      elevations result in abnormal presentation of thyroid antigens to immune cells,
      and that iodide and/or methimazole (MMI) are effective therapeutic agents
      because, at least in part, of their suppression of MHC expression. In this
      report, we show that Graves' patients pretreated with iodide only 4 days before
      surgery have lower levels of MHC class I and class II RNA levels in their thyroid
      tissue than do patients with no iodide pretreatment (P < 0.001 and 0.03,
      respectively). Because patients in both groups are treated with MMI and because
      the change is independent of the amounts of MMI used to treat patients, the class
      I and class II changes cannot be ascribed to MMI. The iodide action to decrease
      MHC class I and class II RNA levels was duplicated using cultured human thyroid
      cells in vitro; the iodide effect was dependent on the iodide concentration, was
      not duplicated by chloride, was not associated with an alteration in cAMP levels
      or with a change in thyrotropin receptor RNA levels, and was evident in gamma
      interferon-treated cells. The data suggest, therefore, that the therapeutic
      action of iodide in Graves' patients is associated with decreased MHC gene
      expression, that this action is a direct effect of high concentrations of iodide
      on the thyroid cells, and that altered MHC gene expression in the target tissue
      may well be associated with the development or perpetuation of Graves' disease.

PMID- 8855813
TI  - Modulation of insulin-like growth factor (IGF) action by IGF-binding proteins in
      normal, benign, and malignant smooth muscle tissues.
AB  - The insulin-like growth factor (IGF) system is involved in the growth of uterine
      leiomyomas (L), as these tumors have higher IGF-II messenger ribonucleic acid
      levels, type I IGF receptor levels, and IGF-I peptide concentrations than
      myometrium (M). Furthermore, cultured L smooth muscle cells (SMC) respond with
      greater efficiency to IGF-I than M SMC. Here we investigate a possible modulating
      role of the binding proteins for the IGFs (IGFBPs) on the actions of IGFs. IGFBP
      3 is the most predominant IGFBP in conditioned medium from SMC, with levels
      ranging from 13-288 ng/mL. Incubation of SMC cultures with IGF-I and the IGF-I
      analogs long-R3IGF-I and des(1-3)-IGF-I, which have decreased affinity for
      IGFBPs, revealed a facilitating effect of IGFBPs on the growth-stimulating
      activity of a high concentration of IGF-I in cell lines with high IGFBP-3 levels.
      Both a decreased level of IGFBP-3 and a low concentration of the growth factors
      added were a disadvantage for the facilitating effect. In M and L tissue
      sections, IGFBP-3 was found exclusively bound to the constituting cells, not in
      the extracellular matrix. This suggests that a negative modulating role of IGFBP
      3 due to sequestration of IGF-I, as occurs in culture medium, is less relevant in
      vivo. In leiomyosarcoma sections, IGFBP-3 levels are decreased, indicating a
      decreasing, role for this binding protein in malignant smooth muscle tissues.

PMID- 8855814
TI  - p53 mutations in adrenal tumors: Caucasian patients do not show the exon 4 "hot
      spot" found in Taiwan.
AB  - Mutations in the p53 tumor suppressor gene are frequently present in human
      cancers but have rarely been described in benign tumors. We previously reported
      mutations in the "hot spots" between exons 5-8 of the p53 gene in adrenocortical
      carcinomas but not in adenomas. Recently, a previously unknown hot spot in exon 4
      of the p53 gene was described in adrenal adenomas and pheochromocytomas of
      Taiwanese patients. We, therefore, investigated whether these mutations are also
      present in Caucasian patients from the U.S. and Europe. We analyzed tumor tissue
      of 12 aldosterone-producing adenomas, 7 cortisol-producing adenomas, and 6
      pheochromocytomas. Overexpression of the p53 protein was investigated by
      immunohistochemistry. Point mutations within exon 4 were identified by polymerase
      chain reaction (PCR) amplification and direct sequencing of the PCR product. The
      pYNZ22 microsatellite located on chromosome 17p, close to the p53 gene, was used
      to screen for allelic loss (LOH) of the p53 gene. Overexpression of p53 was not
      identified in any of the adenomas and pheochromocytomas. Point mutations within
      exon 4 were found in 0/25 tumors. LOH was present in 1/13 informative adenomas
      and 0/2 informative pheochromocytomas. We conclude that p53 mutations do not play
      a major role in the tumorigenesis of adrenal adenomas and pheochromocytomas of
      Caucasian patients. Thus, ethnic and environmental factors may be responsible for
      the mutational spectrum found in Taiwanese patients.

PMID- 8855815
TI  - Short-term estradiol treatment enhances pituitary-adrenal axis and sympathetic
      responses to psychosocial stress in healthy young men.
AB  - Evidence from animal studies and clinical observations suggest that the activity
      of the pituitary-adrenal axis is under significant influence of sex steroids. The
      present study investigated how a short term elevation of estradiol levels affects
      ACTH, cortisol, norepinephrine, and heart rate responses to mental stress in
      healthy men. In a double blind study, 16 men received a patch delivering 0.1 mg
      estradiol/day transdermally, and age- and body mass index-matched control
      subjects received a placebo patch. Twenty-four to 48 h later, they were exposed
      to a brief psychosocial stressor (free speech and mental arithmetic in front of
      an audience). In response to the psychosocial stressor, ACTH, cortisol,
      norepinephrine, and heart rate were increased in both experimental groups (all P
      < 0.0001). However, the estradiol-treated subjects showed exaggerated peak ACTH
      (P < 0.001) and cortisol (P < 0.002) responses compared to the placebo group.
      Also, the norepinephrine area under the response curve was greater in the
      estradiol group (P < 0.05). Although heart rate responses differences failed to
      reach statistical significance, they, too, tended to be larger in the estradiol
      group. Neither mood ratings before or after the stressor, nor ratings of the
      perception of the stressor could explain the observed endocrine response
      differences. In conclusion, short term estradiol administration resulted in
      hyperresponses of the pituitary-adrenal axis and norepinephrine to psychosocial
      stress in healthy young men independent of psychological effects, as assessed in
      this study.

PMID- 8855816
TI  - Metabolism of 5 alpha-dihydroprogesterone in women and men: 3 beta- and 3 alpha
      ,6 alpha-dihydroxy-5 alpha-pregnan-20-ones are major urinary metabolites.
AB  - The metabolism of 5 alpha-dihydroprogesterone (5 alpha-DHP) in women and men was
      evaluated by defining the pattern and identity of selected metabolites excreted
      in urine after the iv infusion of radiolabeled 5 alpha-DHP. Virtually all of the
      radioactivity in urine (approximately 37% of the administered dose) was excreted
      within 72 h. Quantitatively, the 2 major urinary metabolites of 5 alpha-DHP in
      each of 13 studies conducted in 7 women and 2 men were 3 beta,6 alpha-dihydroxy-5
      alpha-pregnan-20-one and 5 alpha-pregnane-3 alpha,20 alpha-diol, which could be
      extracted after beta-glucuronidase, but not solvolysis, treatment of the urine.
      Radiolabeled 3 alpha,6 alpha dihydroxy-5 alpha-pregnan-20-one (glucuronoside), in
      lesser amounts, also was identified in the urine of each subject. The 3
      alpha/beta, 6 alpha-dihydroxy-5 alpha-pregnan-20-ones arise through specific
      extrahepatic pathways of progesterone/5 alpha-DHP metabolism. These metabolites
      are not the products of the enzyme reaction catalyzed by the cytochrome P450
      steroid 6 alpha-hydroxylase of human liver (and other tissues), which affects the
      6 alpha-hydroxylation of C19- and C21-delta 4-3-ketosteroids (e.g., progesterone,
      testosterone, and cortisol), but does not act upon 5 alpha-reduced steroids.
      Moreover, the steroid 5 alpha-reductases do not act upon 6 alpha-hydroxy-delta 4
      3-ketosteroids. In addition, the 6 alpha-hydroxylation of 5 alpha-reduced-3
      alpha/beta-hydroxysteroids is not demonstrable in adult liver tissue. Rather, the
      formation of 6 alpha-hydroxylated-5 alpha-pregnane-3 alpha/beta-ol-20-ones is
      indicative of an extrahepatic pathway of progesterone metabolism, viz.
      progesterone-->5 alpha-DHP-->5 alpha-pregnan-3 beta/alpha-ol-20-one(s)-->3
      beta/alpha,6 alpha-dihydroxy-5 alpha-pregnan-20-one(s), in which 5 alpha-pregnan
      3 alpha/beta-ol-20-ones are metabolized by an enzyme(s) that catalyzes the 6
      alpha-hydroxylation of saturated substrates. There are important differences
      among mammalian species in the enzymes that catalyze the C-6-hydroxylation of 5
      alpha-reduced C19- and C(21)-3 beta/alpha-hydroxysteroids, but in all species
      studied, these enzymatic reactions are the final steps in the extrahepatic
      inactivation of 5 alpha-reduced bioactive metabolites of progesterone (or
      testosterone).

PMID- 8855817
TI  - Antineoplastic activity of taxol against human anaplastic thyroid carcinoma cell
      lines in vitro and in vivo.
AB  - Anaplastic thyroid carcinoma is a rapidly fatal neoplasm that fails to adequately
      respond to any known chemotherapeutic regimen. We tested taxol (paclitaxel)
      against six human anaplastic thyroid carcinoma cell lines (DRO-90, ARO-81, KAT-4,
      KAT-18, SW-1736, and BHT-101). Each cell line monolayer culture, in log phase
      growth, was treated with taxol concentrations ranging from 0.001-5.0 mumol/L.
      Cell numbers, after 24-, 48-, and 72-h growth periods in separate experiments,
      were expressed as percentages of control cell numbers without taxol. All cell
      lines showed maximal inhibition with 0.05 mumol/L taxol at 3-28% of control cell
      numbers. Greater inhibition was seen with longer growth periods. Three cell lines
      (DRO-90, ARO-81, and KAT-4) were grown as sc xenograft tumors in nude mice for 18
      26 days. Treatment groups received sc taxol injections in sites distant from the
      tumors, whereas control mice received vehicle. All taxol-treated xenografts were
      inhibited to near-starting volume or disappeared, whereas control xenograft
      volumes increased 9- to 59-fold. These results suggest that taxol may have
      beneficial clinical effects in anaplastic thyroid carcinoma patients.

PMID- 8855818
TI  - Sublingual testosterone replacement improves muscle mass and strength, decreases
      bone resorption, and increases bone formation markers in hypogonadal men--a
      clinical research center study.
AB  - To study the effects of androgen replacement therapy on muscle mass and strength
      and bone turnover markers in hypogonadal men, we administered sublingual
      testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal
      men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.:
      Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12).
      Subjects who had received prior T therapy were withdrawn from injections for at
      least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle
      strength, and serum and urinary bone turnover markers were measured before and
      after 6 months of SLT. We have shown previously that this regimen for 60 days
      will maintain adequate serum T levels and restore sexual function. Total body (P
      = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34
      subjects in whom body composition was assessed. There was no significant change
      in total body fat or percent fat. The increase in lean body mass was mainly in
      the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to
      9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was
      associated with increased leg muscle strength, assessed by leg press (0 months,
      139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in
      hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029)
      and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with
      increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen
      cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen
      equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol
      BCE/mmol) and was significantly decreased in response to SLT treatment at 6
      months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in
      urinary creatinine. Serum skeletal alkaline phosphatase did not change. In
      addition, SLT replacement caused significant increases in serum osteocalcin (P =
      0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change
      during the 6 months of SLT treatment. We conclude that SLT replacement therapy
      resulted in increases in lean muscle mass and muscle strength. Like estrogen
      replacement in hypogonadal postmenopausal females, androgen replacement therapy
      led to decreased bone resorption and urinary calcium excretion. Moreover,
      androgen replacement therapy may have the additional benefit of increasing bone
      formation. A longer term study for several years duration would be necessary to
      demonstrate whether these changes in bone turnover marker levels will result in
      increased bone mineral density decreased fracture risks, and reduced frailty in
      hypogonadal men.

PMID- 8855819
TI  - Loss of chromosome arm 9p DNA and analysis of the p16 and p15 cyclin-dependent
      kinase inhibitor genes in human parathyroid adenomas.
AB  - Rearrangement and overexpression of the PRAD1/cyclin D1 oncogene, a cell cycle
      regulator, have been implicated in the pathogenesis of a subset of parathyroid
      adenomas. Recently, two cell cycle regulators that inhibit the cyclin D1
      associated kinases cdk4 and cdk6 have been identified: p16 and p15, the products
      of the INK4A (also known as CDKN2, MTS1) and INK4B (also known as MTS2) putative
      tumor suppressor genes located on 9p21. Because inactivation of the p16 or p15
      genes might be expected to result in oncogenic consequences similar to those from
      cyclin D1 overexpression, we examined 25 parathyroid adenomas for 1) allelic loss
      of polymorphic DNA loci on chromosome arm 9p, 2) homozygous deletions of the p16
      and p15 genes by Southern blot analysis, and 3) mutations of the p16 and p15
      genes by single strand conformational polymorphism analysis. Heterozygous allelic
      loss at 9p was observed in 4 of 25 adenomas (16%); their smallest shared region
      of deletion was 9p21-pter, which includes both the p16 and p15 genes. However,
      single strand conformational polymorphism analysis of all 3 exons of the p16 gene
      and both exons of the p15 gene failed to demonstrate mutation in any of the 25
      cases, and homozygous deletions of the p16 and p15 genes, which are present in
      some human cancers, were not found in any parathyroid tumors. These observations
      indicate that inactivating mutations or homozygous deletions of the p16 and p15
      genes occur uncommonly, if ever, in parathyroid adenomas; however, loss of a
      different tumor suppressor gene (or genes) on 9p appears to contribute to the
      pathogenesis of a significant percentage of these tumors.

PMID- 8855820
TI  - Growth of short children during and after discontinuation of growth hormone
      therapy.
AB  - We have attempted to evaluate the relationship between spontaneous growth hormone
      (GH) secretion and the response to GH therapy as well as the effect of
      discontinuation of GH therapy on further growth. The 24-h integrated
      concentration of GH (ICGH) was determined in 150 short children (< 2 SD for age)
      with a GH response to clonidine stimulation of more than 10 mcg/L. The patients
      were treated with GH for 4 yr and were observed for 1 yr following cessation of
      GH treatment. Twenty-two out of 52 patients who had an ICGH of less than 3.2
      mcg/L (group LICGH) and 28 out of 60 patients who had an ICGH of more than 3.2
      mcg/L (group NICGH) were followed without GH therapy. Only patients who remained
      prepubertal throughout the study were included in the analysis. The growth
      response of the LICGH to GH was better than that of the NICGH children. Patients
      regained normal growth velocity 6-12 months after discontinuation of GH therapy.
      Three children of the LICGH subsequently developed classic GH deficiency. These
      studies demonstrate that short-term GH therapy can improve the growth channel.
      Children with a low ICGH grow better on GH than children with a normal ICGH.
      Children with a low ICGH need continued observation and retesting when growth
      velocity is low.

PMID- 8855821
TI  - Hospitalization and expenditures for the treatment of general medical conditions
      among the U.S. diabetic population in 1991.
AB  - Although the medical expenditures for the treatment of acute glycemic and chronic
      complications of diabetes are well documented, little is known about the costs of
      treating general medical conditions among persons with diabetes. Accordingly,
      data from the 1991 National Hospital Discharge Survey and the 1987 National
      Medical Expenditure Survey were used to estimate the risk of hospitalization for
      general medical conditions among middle-aged (45-64 yr) and elderly (> or = 65
      yr) persons with diabetes and the associated in-patient expenditures attributable
      to diabetes in the United States. In 1991, there were 371,814 hospitalizations of
      middle-aged persons with diabetes and 712,725 hospitalizations of elderly persons
      with diabetes for treatment of general medical conditions. Both middle-aged and
      elderly persons with diabetes remained hospitalized longer than their nondiabetic
      peers (8.1 vs. 6.3 days and 10.1 vs. 8.9 days, respectively). Compared to their
      nondiabetic peers, middle-aged persons with diabetes were at greatest risk of
      hospitalization for peritonitis/intestinal abscess [relative risk, 13.1; 95%
      confidence interval (CI), 12.5-13.8] and respiratory failure (relative risk, 5.0;
      95% CI, 4.9-5.1) and elderly persons with diabetes were at greatest risk of
      hospitalization for liver diseases (relative risk, 3.0; 95% CI, 2.9-3.0) and
      septicemia (relative risk, 2.8; 95% CI, 2.8-2.9). In-patient expenditures for the
      treatment of general medical conditions attributable to diabetes were estimated
      at +4.12 billion, nearly twice the in-patient expenditures incurred for the
      treatment of chronic complications of diabetes. These results demonstrate the
      disproportionate resources devoted to treating patients with diabetes for
      conditions that are neither acute glycemic nor chronic complications of diabetes.

PMID- 8855822
TI  - Truncation at the C-terminus of the DAX-1 protein impairs its biological actions
      in patients with X-linked adrenal hypoplasia congenita.
AB  - The DAX-1 [DSS (dosage-sensitive sex)-AHC critical region in the X, gene 1] gene
      has been reported to be responsible for X-linked adrenal hypoplasia congenita
      (AHC) and hypogonadotropic hypogonadism. However, the function and structure of
      the DAX-1 protein have not been characterized. In this study, molecular analysis
      of the DAX-1 gene from 6 patients with AHC, including 2 siblings, identified 5
      novel mutations with 3 nonsense mutations and 2 frameshift mutations. Case 1 had
      a nonsense mutation at position 395 (Q395X). Cases 2 and 3, who were siblings,
      had a nonsense mutation at position 91 (Y91X). Case 4 had a 2-base deletion (AT)
      at nucleotides 1610 and 1611 and a 1-base insertion (G) resulting in a premature
      stop codon at position 462 (1610-1611 del AT ins G). Case 5 had a nonsense
      mutation at position 271 (Y271X). Case 6 had a 1-base deletion (C) at nucleotide
      1169, which induced a frame shift and a premature stop codon at position 371
      (1169 del C). All mutated DAX-1 proteins had truncated C-terminal domains. In
      addition, reverse transcription-PCR and direct sequencing characterized the
      mutant messenger ribonucleic acid in testis from case 1. Our results suggest that
      these 5 novel mutations are responsible for X-linked AHC and that the C-terminus
      of the DAX-1 protein, especially the terminal 11 amino acids, is necessary for
      normal adrenal cortical embryogenesis.

PMID- 8855823
TI  - A mechanism for the suppression of estrogen production in polycystic ovary
      syndrome.
AB  - In polycystic ovary syndrome (PCOS), follicle development arrests in the early
      antral stage when aromatase expression in the granulosa cells (GC) would normally
      occur. Despite high intrafollicular concentrations of androstenedione and
      bioactive FSH, in vivo estrogen biosynthesis remains low. When GC from PCOS
      follicles are stimulated with FSH in vitro, a marked stimulation of estrogen
      production occurs, suggesting that PCOS follicles contain an endogenous inhibitor
      of estrogen production. To test this hypothesis, GC from hyperstimulated women
      were cultured with increasing concentrations of follicular fluid (FF) from PCOS
      and normally cycling control women in the presence of androstenedione (10(-5)
      mol/L). FF from control women caused a small decrease (20%) in estradiol
      production. PCOS FF caused a dose-related inhibition of estradiol production
      (60%), indicating that there was significantly more inhibitory activity in PCOS
      FF. To determine whether abnormal androgen metabolism could play a role in
      inhibiting estradiol production in PCOS, we measured 5 alpha-androstane-3, 17
      dione, a competitive inhibitor of aromatase activity, in serum and FF of control
      and PCOS women. 5 alpha-Androstane-3, 17-dione levels in serum were significantly
      elevated in PCOS. 5 alpha-Androstane-3, 17-dione levels were 1000-fold higher in
      PCOS FF than serum. Moreover, FF levels were markedly higher in PCOS follicles (P
      < 0.0001) than in normal dominant and cohort follicles. Dose-response studies
      revealed that the concentration of 5 alpha-androstane-3, 17-dione present in FF
      form normal dominant follicles (79.4 +/- 14.6 nmol/L) had little effect on
      estradiol production. In contrast, 5 alpha-androstane-3, 17-dione levels in PCOS
      FF (581.6 +/- 62.9 nmol/L) inhibited estradiol production by 75%. These data
      support the hypothesis that PCOS FF contains one or more endogenous inhibitors of
      aromatase activity and suggest that abnormally high 5 alpha-androstane-3, 17
      dione levels in PCOS FF may be an important inhibitor of estradiol production.

PMID- 8855824
TI  - Inhibin B in males with gonadotropin-releasing hormone (GnRH) deficiency: changes
      in serum concentration after shortterm physiologic GnRH replacement--a clinical
      research center study.
AB  - To examine the role of inhibin B in the feedback regulation of FSH secretion in
      the human male, we determined serial levels in 18 men with idiopathic
      hypogonadotropic hypogonadism (IHH) during their initial 8 weeks of GnRH
      replacement. Pulsatile GnRH was administered every 2 h, with the dose increased
      at 2-week intervals (5-50 ng/kg/bolus). Every 2 weeks, sera were assayed for
      inhibin B, FSH, LH, and testosterone. Serial comparisons were performed within
      the IHH group as well as vs. normal men (n = 20). The baseline inhibin B level in
      IHH patients averaged 68 +/- 11 pg/mL (mean +/- SEM), significantly less than
      that in normal men (239 +/- 14 pg/mL; P < 0.001). After 8 weeks of pulsatile
      GnRH, inhibin B levels in the IHH patients increased significantly to 118 +/- 14
      pg/mL (P = 0.003). During GnRH replacement, FSH concentrations correlated
      negatively with inhibin B concentrations at all doses. Patients previously
      treated with testosterone began with somewhat lower inhibin B levels but
      demonstrated a significantly greater increase in serum concentrations than
      patients who had received prior gonadotropin or GnRH therapy. A history of
      cryptorchidism did not have a significant impact on inhibin B concentrations
      before or during GnRH replacement. The low inhibin B levels in IHH men at
      baseline and their prompt increase in response to pulsatile GnRH suggest acute
      regulation by gonadotropin stimulation of the testis. The variation in inhibin B
      levels at baseline and in response to GnRH suggest that prior gonadotropin
      exposure and seminiferous tubular development also modulate inhibin B secretion.
      The consistent negative correlation between FSH and inhibin B during the
      induction of sexual maturation with GnRH supports the role of gonadal inhibin B
      secretion as an important endocrine regulator of FSH in the human male.

PMID- 8855825
TI  - Low levels of sex hormone-binding globulin and testosterone are associated with
      smaller, denser low density lipoprotein in normoglycemic men.
AB  - Recently, the phenotype with a preponderance of small, dense low density
      lipoprotein (LDL) has been associated with increased coronary heart disease.
      Although previous data indicated that decreased sex hormone-binding globulin
      (SHBG) and testosterone concentrations are associated with increased triglyceride
      and decreased high density lipoprotein (HDL) cholesterol levels in men, no data
      are available on the relationship of LDL composition to sex hormones. Therefore,
      we examined the relationship of SHBG, total and free testosterone, estradiol, and
      dehydroepiandrosterone sulfate to LDL size (as determined by gradient gel
      electrophoresis) in 87 normoglycemic men. LDL size was significantly positively
      related to SHBG (r = 0.354) and total testosterone (r = 0.313) and inversely
      related to dehydroepiandrosterone sulfate (r = -0.247), but not to free
      testosterone or estradiol concentrations. After adjustment for age, waist
      circumference, overall glucose disposal, fasting glucose, triglyceride, and HDL
      cholesterol, LDL size remained significantly associated with SHBG (r = 0.312) and
      total testosterone (r = 0.269). The relationship between LDL size and total
      testosterone and SHBG tended to be stronger in nonobese subjects. We conclude
      that SHBG and total testosterone concentrations are significantly associated with
      LDL size in men, and these relationships appear to be independent of known
      confounding variables, such as triglyceride and HDL cholesterol levels. Our data
      suggest that endogenous sex hormones may have an independent modifying effect on
      LDL composition in men.

PMID- 8855826
TI  - Normal hepatic insulin sensitivity in lean, mild noninsulin-dependent diabetic
      patients.
AB  - We studied hepatic and extrahepatic insulin sensitivity and insulin release in
      seven nonobese patients with mild noninsulin-dependent diabetes mellitus (NIDDM)
      and 10 control subjects, matched for age, body mass index, and physical fitness.
      Glucose turnover was studied during sequential hyperinsulinemic euglycemic clamps
      (insulin infusion, 0.25 and 1.0 mU/kg BW.min), applying the hot-GINF (tracer
      enriched glucose infusion) technique and using [6-3H]glucose. Hepatic glucose
      production was lower in hyperglycemic NIDDM patients during the basal period (P <
      0.01), but was equivalent at similar glucose and insulin levels attained during
      both clamps. In contrast, during the low and high insulin clamps, glucose
      utilization was lower in NIDDM [14.90 +/- 1.00 vs. 17.24 +/- 0.83 (P < 0.01) and
      41.37 +/- 3.05 vs. 50.54 +/- 3.61 mumol/kg BW.min (P < 0.01)]. Accordingly, the
      glucose infusion rate necessary to maintain euglycemia was lower in NIDDM [7.72
      +/- 2.00 vs. 10.68 +/- 1.17 (P < 0.05) and 42.14 +/- 4.50 vs. 51.60 +/- 4.28
      mumol/kg BW.min (P < 0.01)]. There was, however, a considerable overlap between
      patients and controls in the parameters describing insulin sensitivity. The
      insulin response to orally administered glucose as well as that to a standardized
      glucose infusion test (GIT) were diminished in NIDDM [average incremental insulin
      secretion during an oral glucose tolerance test, 88 +/- 28 vs. 251 +/- 50
      pmol/L.min (P < 0.05); during first 10 min of GIT, 7 +/- 16 vs. 234 +/- 29
      pmol/L.min (P < 0.001)]. There was no overlap in acute phase insulin secretion
      during the GIT between the groups. In conclusion, nonobese, mild NIDDM patients
      showed no impairment in hepatic, but a slight reduction in extrahepatic insulin
      sensitivity, with extensive overlap between diabetic and control subjects. In
      contrast, impairment of insulin release was very pronounced and without overlap.

PMID- 8855827
TI  - The effect on the insulin-like growth factor system in human prostate epithelial
      cells of immortalization and transformation by simian virus-40 T antigen.
AB  - The insulin-like growth factor (IGF) system has been demonstrated to be important
      for proliferation and differentiation in tissues. This system has also been
      demonstrated to be an important regulator of the growth of normal prostate
      epithelium and has been implicated in the process of transformation to human
      epithelial prostate cancer. This study examined the function of the various
      components of the IGF system in benign prostate epithelium (BPE), simian virus-40
      (SV40)-T antigen-immortalized prostate epithelial cells, P69SV40-T (P69), and two
      sublines generated from the parental line by serial passage through athymic mice:
      one tumorigenic (M2182) and one metastatic (M12). IGF-II messenger ribonucleic
      acid (mRNA) and protein were detected in BPE cells, and each of the three P69
      cell lines. IGF-II protein levels were significantly higher in medium collected
      from the P69, M2182, and M12 cells than in BPE. Proliferation in response to IGF
      was P69 > BPE > M2182 > M12. The proliferative responses in the four cell types
      were paralleled by an increase in c-jun. In addition, as the cells became
      progressively more tumorigenic, the basal level of c-jun mRNA increased. IGF
      binding protein-2 (IGFBP-2), -3, -4, -5, and -6 could be detected in the primary
      epithelial cell medium; however, as the cells became progressively more
      tumorigenic, there was a decrease in IGFBP-2, -3, -5, and -6 in the medium. The
      type 1 IGF receptor (IGFr) also decreased as the cells became more tumorigenic.
      The M12 cells had 80% fewer receptors than the P69 cells and 70% fewer than M2182
      cells. There was no change in the Kd for IGF between the cell lines. Based on
      these data it would appear that the difference in proliferation between the BPE
      cells and P69s may be due to an increased concentration of inhibitory IGFBPs in
      the P69 medium. The decrease in proliferation seen in response to IGF in M2182
      and M12 cells compared to the P69s would appear at least in part to be due to a
      decreased IGFr number. IGFr mRNA is represented by 11.0- and 7.0-kilobase bands
      in the BPE and P69 cells, but only by an 11.0-kilobase band in M2182 and M12
      cells. These data indicate that there are significant changes that occur in the
      IGF system during the process of malignant transformation of the prostate
      epithelium. The changes described in the P69 cell system are similar to those
      seen in vivo and suggest that an intact IGF system may be important in
      maintaining a differentiated epithelial cell.

PMID- 8855828
TI  - Different responses of free and peptide-bound cross-links to vitamin D and
      calcium supplementation in elderly women with vitamin D insufficiency.
AB  - Recent findings have shown that bisphosphonates had different effects on the
      urinary excretion of free and peptide-bound cross-links. Because of this
      discrepancy, we investigated the effects of another antiresorptive therapy, i.e.
      vitamin D (vitD) and calcium (Ca) supplementation (800 IU vit D3 and 1 g
      elemental calcium daily for 6 months) in elderly women (n = 21, age: 83.5 +/- 1.5
      yr) with vitD insufficiency and secondary hyperparathyroidism (mean level 25
      hydroxy vitamin D = 3.17 +/- 1.2 ng/mL, mean level of intact parathormone = 45.3
      +/- 22.7 pg/mL) on the urinary excretion of free and peptide-bound cross-links. A
      group of free-living, healthy elderly women (n = 25, age: 76.6 +/- 3.1 yr) with a
      normal vitD status (mean level of 25 OH D = 23.4 +/- 8.9 ng/mL, intact
      parathormone = 30.2 +/- 11.2 pg/mL) was simultaneously studied. Bone resorption
      was assessed by total (T), free (F), peptidyl (P) hydroxylysylpyridinoline (HP)
      and lysylpyridinoline (LP) measured with high performance liquid chromatography,
      by F-LP determined with enzyme linked immunosorbent assay (iF-LP) and by the N-
      and C-terminal telopeptides of type I collagen (NTX and Cross-laps) before and
      after (3 and 6 months) therapy. Comparison of the two groups of elderly women at
      baseline showed that the urinary excretion of pyridinoline cross-links (T, F, and
      peptide-bound forms) and of telopeptide fragment of type I collagen were all
      increased in patients with a low vitD status. Highly significant differences were
      seen principally for T-HP, F-HP, and F-LP (P < 0.001). Correlation studies
      between each marker showed that the values of pyridinoline cross-links (T and
      peptide-bound forms) and of the telopeptide fragments of type I collagen
      correlated well, but the correlation was slightly less pronounced between free
      pyridinolines and the other markers. After treatment, the response to therapy was
      greatest for peptide-bound cross-links assessed by high performance liquid
      chromatography and for telopeptide fragments of type I collagen (percent change
      at 6 months: -21% for P-HP P < 0.05, -26% for P-LP P < 0.05, -31% for NTX P <
      0.01, and -51% for CLaps P < 0.001). In contrast, free pyridinolines excretion (F
      HP and F-LP) assessed by high performance liquid chromatography as well as by
      immunoassay remained unchanged at 3 and 6 months. Because marked and significant
      changes were seen with peptide-bound cross-links only and not with free forms, we
      conclude that vitD and Ca therapy has the same effects as bisphosphonates on the
      urinary excretion of free and peptide-bound cross-links. So far, no rational
      mechanism can be given to explain this discrepancy, and further studies are
      needed before routine application of these bone collagen degradation products as
      bone resorption markers.

PMID- 8855829
TI  - Clinical features of primary ovarian failure caused by a point mutation in the
      follicle-stimulating hormone receptor gene.
AB  - The recent finding that a mutation in the FSH receptor gene causes ovarian
      dysgenesis prompted the present study to determine the phenotype caused by this
      mutation. Twenty-two patients with ovarian dysgenesis and a 566C-->T mutation in
      the FSH receptor gene (designated FSH-resistant ovaries or FSHRO) were compared
      with 30 clinically similar patients with ovarian dysgenesis (designated ODG) who
      did not have this mutation. The genealogical studies suggested a founder effect
      of the FSH receptor gene mutation in Finland. Clinically, both groups of patients
      were characterized by primary or early secondary amenorrhea, variable development
      of secondary sex characteristics, and high serum levels of FSH and LH. Notable
      differences were observed in median adult height (FSHRO patients were shorter)
      and the occurrence of follicles judged by transvaginal sonography (observed in 6
      of 8 FSHRO vs. 1 of 11 ODG) and ovarian histology (present in all 9 FSHRO vs. 1
      of 4 ODG). These findings suggest that a subset of ovarian dysgenesis patients
      with the FSH receptor mutation 566C-->T is pathogenetically distinct, possibly
      due to residual receptor activity, and that these patients can be tentatively
      identified by demonstrating the presence of ovarian follicles and confirmed by
      mutation analysis.

PMID- 8855830
TI  - Benfluorex in obese noninsulin dependent diabetes mellitus patients poorly
      controlled by insulin: a double blind study versus placebo.
AB  - Most obese patients with noninsulin-dependent diabetes mellitus (NIDDM) are
      initially treated with diet, then with oral hypoglycemic agents, eventually with
      insulin. However several reports indicate that in these patients insulin therapy
      has little chance to control glucose metabolism, promotes weight gain and
      arterial hypertension, and is likely to aggravate insulin resistance. In this
      randomized, double-blind trial vs. placebo (P) we evaluated in 29 obese NIDDM
      patients poorly controlled by insulin (daily insulin doses 48.7 +/- 4.0 U/day,
      HbA1c 10 +/- 0.27%, mean daily blood glucose levels 12.3 +/- 0.3 mmol/L, fasting
      C-peptide 1.8 +/- 0.2, C-peptide after 1 mg iv glucagon 3.2 +/- 0.3 ng/mL, means
      +/- SE), the clinical and metabolic effects of benfluorex (B), a lipid-lowering
      drug able to improve insulin sensitivity. After a 2-3 week run-in period (1
      tablet P at dinner and diet 800 cal/day to lose 5% of the initial body weight
      (BWi), patients received a 1000 kcal/day diet and were randomized to B, 150 mg/
      tablet, or P (3 tablets/day); the time limit was set at a 10% decrease of BWi or
      at 90 days. At the end of run-in there was a significant reduction of BWi (P <
      0.001), fasting (P = 0.002) and mean daily blood glucose levels (P < 0.001),
      triglycerides (P = 0.02), cholesterol (P < 0.001) and daily insulin doses (P <
      0.001). At the end of the double-blind trial, weight-loss was greater (P < 0.05),
      faster (P = 0.018), and more frequent (P < 0.05) with B than with P, and systolic
      blood pressure (P < 0.05) decreased only with B. Considering only patients with a
      10% decrease of BWi (B = 15, P = 10), HbA1c (P < 0.001) decreased only with B,
      while fasting insulin levels decreased with both B (P < 0.01) and with P (P <
      0.05). Insulin sensitivity was evaluated by means of a double infusion test
      (LDIGIT, insulin 25 mU/Kg/h plus glucose 4 mg/kg/min, lasting 150 min) at the end
      of run-in and at the end of the double-blind trial; at the end of the double
      blind trial steady state blood glucose (SSBG, P < 0.05), free fatty acids (FFA, P
      < 0.05) and blood beta-hydroxybutyrate (P < 0.05) decreased only with B, while
      blood glycerol decreased both with both P (P < 0.05) and B (P < 0.06). At the end
      of the double-blind trial, C-peptide release was unchanged with either P or B. In
      conclusion, benfluorex potentiates the effects of hypocaloric diet on weight loss
      and on glycemic control in obese NIDDM patients treated with insulin, and this
      effect seems to be the result of an improved insulin sensitivity.

PMID- 8855831
TI  - Antigen receptor variable region repertoires expressed by T cells infiltrating
      thyroid, retroorbital, and pretibial tissue in Graves' disease.
AB  - To date, it has remained unclear whether T cells infiltrating thyroid,
      retroorbital, and pretibial tissue of patients with Graves' ophthalmopathy and
      pretibial dermopathy represent a primary immune response that is directed against
      certain antigenic determinants shared among these involved tissues. To
      characterize these T cells at the molecular level, we compared the T cell antigen
      receptor (TcR) variable (V) region gene usage in thyroid, retroorbital, pretibial
      tissue, and peripheral blood mononuclear cells of two patients with Graves'
      disease, ophthalmopathy, and pretibial dermopathy. Ribonucleic acid was
      extracted, reverse transcribed, and amplified using the PCR and 22 V alpha and 23
      V beta gene-specific oligonucleotide primers. The resulting TcR V alpha and V
      beta transcripts were verified by Southern hybridization analysis using TcR C
      region-specific, digoxigenin-labeled oligonucleotide probes. In addition,
      complementarity determining regions 3 and junctional regions of TcR V beta genes
      were sequenced. Marked similarities of intrathyroidal, retroorbital, and
      pretibial TcR V alpha and V beta gene repertoires were noted with respect to the
      degree of TcR V gene restriction and the patterns of individual V genes
      expressed. Sequence analysis of junctional domains of V beta families revealed
      oligoclonality of intrahyroidal, retroorbital, and pretibial T cells. In
      addition, certain conserved junctional motifs were shared by T cells derived the
      thyroid gland and the extrathyroidal sites. Our results suggest that in the two
      patients with Graves' disease and extrathyroidal manifestations studied, similar
      antigenic determinants may have contributed to the recruitment and oligoclonal
      expansion of T cells both within the thyroid gland and at the involved
      extrathyroidal sites.

PMID- 8855832
TI  - Relevance of RET proto-oncogene mutations in sporadic medullary thyroid
      carcinoma.
AB  - Analysis of peripheral blood or tumor DNA samples from 101 patients with apparent
      sporadic medullary thyroid carcinoma (MTC) was performed to assess the frequency
      of RET proto-oncogene mutations in this patient population. Peripheral blood
      and/or tumor DNA was amplified by polymerase chain reaction. DNA sequence or
      restriction enzyme analysis was performed to detect mutations of RET proto
      oncogene codons 609, 611, 618, 620, 634, 768, and 918. Six of 101 patients with
      apparent sporadic MTC had peripheral blood DNA mutations more commonly associated
      with hereditary MTC. In 4 patients, these mutations led to the identification of
      previously unrecognized kindreds. The remaining 2 patients were examples of de
      novo mutations. A codon 918 mutation was found in 14 of 57 (approximately 25%)
      tumor DNA samples. Mutations were not identified in the remaining patients. In
      this large cancer center population, approximately 6% of patients with sporadic
      MTC carry peripheral blood DNA mutations, either inherited or de novo, more
      commonly associated with MEN 2A or familial MTC. Seven additional gene carriers
      were identified as a direct result of these studies, a 2-fold multiplying effect.
      We conclude routine application of RET proto-oncogene testing should be included
      in all cases of apparent sporadic MTC.

PMID- 8855833
TI  - The orderliness of the growth hormone (GH) release process and the mean mass of
      GH secreted per burst are highly conserved in individual men on successive days.
AB  - Endocrine glands signal their remote target tissues via physiologically pulsatile
      release of regulatory molecules. A cardinal assumption of most pathophysiological
      experiments is that discrete attributes of pulsatile hormone secretion are stable
      over successive untreated observation intervals; i.e. repeated measurements show
      serial within-subject reproducibility. To test this hypothesis in the GH axis, we
      sampled blood every 10 min for 48 h in 14 healthy men (age range, 29-77 yr; body
      mass index, 21-51 kg/m2). The 2 consecutive 24-h serum profiles were subjected to
      ultrasensitive GH chemiluminescence assay (sensitivity, 0.002 micrograms/L) with
      a new dose-dependent variance model to estimate within-assay precision. We then
      applied deconvolution analysis to estimate the number, mass, amplitude, and
      duration of underlying GH secretory bursts as well as simultaneously calculate
      the apparent GH half-life and any concurrent basal hormone secretion. Test-retest
      consistency was assessed by the Pearson correlation coefficient, and differences
      were determined by paired nonparametric (Wilcoxon) testing. Comparing successive
      24-h profiles, no significant differences existed in any of the foregoing
      secretion or half-life measures or in a novel estimate of the relative
      disorderliness of hormone release, namely approximate entropy. Correlation was
      minimal for secretory burst amplitude and half-duration. In contrast, the
      calculated mean mass of GH secreted per burst was highly conserved across
      sessions within subjects, with an r value of 0.932 (P < 10(-6). This correlation
      equaled or exceeded that of mean and integrated serum GH concentrations on
      consecutive days (r = 0.920; P = 0.00003). The calculated daily GH production
      rate was also strongly reproduced (r = 0.784; P = 0.0009). Moreover, the within
      subject GH half-life and GH secretory burst frequency estimates were well
      correlated on successive days (P = 0.034-0.004; r = 0.568-0.711). Approximate
      entropy values were consistent at r = 0.837 (P = 0.0019). In addition, basal GH
      secretion rates correlated at r = 0.622 (P = 0.0176). We conclude that
      homeostatic control mechanisms within the GH-insulin-like growth factor I axis
      strongly preserve the day to day mean mass of GH secreted per burst and the
      serial orderliness of the GH release process in individual healthy men across a
      wide span of ages and body compositions.

PMID- 8855834
TI  - The effects of supraphysiological doses of testosterone on angry behavior in
      healthy eugonadal men--a clinical research center study.
AB  - Anecdotal reports of "roid rage" and violent crimes by androgenic steroid users
      have brought attention to the relationship between anabolic steroid use and angry
      outbursts. However, testosterone effects on human aggression remain
      controversial. Previous studies have been criticized because of the low androgen
      doses, lack of placebo control or blinding, and inclusion of competitive athletes
      and those with preexisting psychopathology. To overcome these pitfalls, we used a
      double-blind, placebo-controlled design, excluded competitive athletes and those
      with psychiatric disorders, and used 600 mg testosterone enanthate (TE)/week.
      Forty-three eugonadal men, 19-40 yr, were randomized to 1 of 4 groups: Group I,
      placebo, no exercise; Group II, TE, no exercise; Group III, placebo, exercise;
      Group IV, TE plus exercise. Exercise consisted of thrice weekly strength training
      sessions. The Multi-Dimensional Anger Inventory (MAI), which includes 5 different
      dimensions of anger (inward anger, outward anger, anger arousal, hostile outlook,
      and anger eliciting situations), and a Mood Inventory (MI), which includes items
      related to mood and behavior, were administered to subjects before, during, and
      after the 10 week intervention. The subject's significant other (spouse, live-in
      partner, or parent) also answered the same questions about the subject's mood and
      behavior (Observer Mood Inventory, OMI). No differences were observed between
      exercising and nonexercising and between placebo and TE treated subjects for any
      of the 5 subdomains of MAI. Overall there were no significant changes in MI or
      OMI during the treatment period in any group. CONCLUSION: Supraphysiological
      doses of testosterone, when administered to normal men in a controlled setting,
      do not increase angry behavior. These data do not exclude the possibility that
      still higher doses of multiple steroids might provoke angry behavior in men with
      preexisting psychopathology.

PMID- 8855835
TI  - Relationships between intact parathyroid hormone 24-hour profiles, sleep-wake
      cycle, and sleep electroencephalographic activity in man.
AB  - To determine whether the 24-h intact PTH (iPTH) profile is influenced by the
      sleep-wake cycle, and whether iPTH pulses show a temporal relationship with
      internal sleep structure, eight normal young men were studied during 24 h under
      basal conditions, once with normal nighttime sleep from 2300-0700 h and once
      after a night of sleep deprivation followed by an 8-h period of daytime sleep
      from 0700-1500 h. During the 8-h nighttime sleep period, mean iPTH levels were
      significantly increased by +13% and mean iPTH pulse amplitudes by +31% as
      compared with the 8-h subsequent waking periods. During the 8 h of total sleep
      deprivation, mean iPTH levels were not significantly different from the
      corresponding period in nighttime sleep condition, but mean iPTH pulse amplitudes
      were significantly lower (P < 0.01). The 8-h daytime sleep period was associated
      with increased mean iPTH levels and mean iPTH pulse amplitudes (+15% and +57%,
      respectively, as compared with the corresponding period in nighttime sleep
      condition). The number of pulses was similar in both experimental series and was
      not influenced by sleep or by time of day. Analysis of coincidence between iPTH
      pulses, plasma ionized calcium and plasma phosphate pulses, and slow wave sleep,
      as well as with rapid eye movement sleep episodes, did not reveal any significant
      association. Cross-correlation analysis between iPTH, plasma ionized calcium, and
      plasma phosphate fluctuations during sleep also showed no systematic association.
      Seven other subjects were studied during a nighttime sleep period in which
      temporal relationships between iPTH and internal sleep structure were reevaluated
      using spectral analysis of the sleep electroencephalogram. Cross-correlation
      analysis between iPTH levels and delta-relative power fluctuations showed
      nonsignificant results, which confirms the lack of relationship with slow wave
      sleep. This study demonstrates that the iPTH 24-h profile is influenced by sleep
      processes with a weak circadian component. However, iPTH pulses are not
      temporally linked with sleep electroencephalographic activity nor with calcemia
      and phosphatemia fluctuations. This evidence raises questions about the origin of
      iPTH pulses.

PMID- 8855836
TI  - Gastrin-releasing peptide-like immunoreactivity is present in human maternal and
      fetal placental membranes.
AB  - Extracts of human term amnion, placenta, and chorion/decidual tissue (n = 5)
      contained gastrin-releasing peptide-like immunoreactivity (GRPLI) in amounts of
      4.7 +/- 2.9 (pmol/g wet wt; mean +/- SEM), 3.6 +/- 1.1 and 2.9 +/- 1.5,
      respectively. Using C-terminally directed antisera and gel filtration
      chromatography and reverse-phase high-performance liquid chromatography (HPLC),
      each tissue contained molecular forms consistent with the presence of GRP1-27 and
      GRP18-27 but also contained larger amounts of two GRPLI peaks, which apparently
      are novel GRP-like peptides. In contrast, tissue extracts of human fetal lung
      contained only GRP1-27, GRP14-27, and GRP18-27. Using RT-PCR and specific GRP
      primers and probes, messenger RNA encoding for GRP was readily demonstrable from
      6-weeks gestation throughout pregnancy to term in full-thickness membranes,
      placental villi, and decidua. Positive immunohistochemical staining for GRP
      occurred in extravillous trophoblasts in decidual septa and fetal membranes,
      cytotrophoblasts, syncytiotrophoblast, and certain stromal cells in placental
      villi and amniotic epithelium. GRPLI and GRP messenger RNA were present from the
      earliest dates examined (6-9 weeks) throughout pregnancy to term. Given the
      proven trophic nature of GRP and related peptides, these peptides may play
      important roles in maternal, placental, and fetal development during human
      pregnancy.

PMID- 8855837
TI  - Protein and messenger ribonucleic acid (mRNA) for the type 1 insulin-like growth
      factor (IGF) receptor is decreased and IGF-II mRNA is increased in human prostate
      carcinoma compared to benign prostate epithelium.
AB  - Insulin-like growth factors (IGFs) and the type 1 IGF receptor (IGF-R) are
      involved in normal growth and development of the human prostate. Changes in
      levels of IGF-R and IGFs have been shown for several malignancies.
      Immunohistochemistry and in situ hybridization were performed to compare the
      expression of IGF-R and IGF-II in vivo in prostate tissue containing benign
      epithelium, high grade prostate intraepithelial neoplasia (PIN), and
      adenocarcinoma. Messenger ribonucleic acid (mRNA) hybridization signals and
      immunoreactivity for IGF-R were localized primarily to epithelial cells, with
      less signal in stroma. IGF-R mRNA was significantly decreased by 42% in PIN and
      35% in cancer cells compared to that in benign epithelium (P < 0.0001). IGF-R
      immunostaining was significantly decreased by 32% in PIN and by 42% in malignant
      epithelium compared to that in benign epithelium (P < 0.004). IGF-II mRNA was
      also localized primarily to epithelial cells. IGF-II mRNA was significantly
      increased by 30% in adenocarcinoma compared to that in benign epithelium (P <
      0.03). Immunoreactivity for IGF-II was localized to both stroma and epithelium.
      Protein levels for IGF-II were not significantly increased in cancer cells
      compared to those in benign epithelium. The decrease in the type 1 IGF receptor
      and increase in IGF-II mRNA may affect prostate cancer proliferation and
      differentiation.

PMID- 8855838
TI  - Insulin-like growth factor-binding proteins (IGFBP)-4, -5, and -6 in the benign
      and malignant human prostate: IGFBP-5 messenger ribonucleic acid localization
      differs from IGFBP-5 protein localization.
AB  - Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the actions
      of IGF. We have previously reported that IGFBP-2 messenger ribonucleic acid
      (mRNA) and protein are increased, and IGFBP-3 protein decreased in malignant
      prostate epithelium compared to benign epithelium. In this study, we examined the
      other IGFBPs secreted by prostate cells in vitro, namely IGFBP-4, -5, and 6.
      Immunoreactivity and mRNA signals for IGFBP-4 and -6 were localized to epithelial
      cells, with less signal in stroma. IGFBP-4 immunostaining and hybridization
      signal were significantly increased in prostate adenocarcinoma compared to those
      in benign epithelium. Immunostaining for IGFBP-5 was localized to the epithelium
      and stroma. IGFBP-5 immunoreactivity was significantly increased in malignant
      compared to benign epithelium. IGFBP-5 mRNA signal was not localized to
      epithelial cells; rather, the signal was over stromal cells surrounding the
      acinar structures. These cells are thought to be fibroblasts. We show that IGFBP
      4 mRNA and protein and IGFBP-5 protein are increased in malignant epithelium
      compared to benign epithelium, that IGFBP-6 is present in benign and malignant
      epithelium, and that there is differential localization of IGFBP-5 mRNA and
      protein in prostate tissue. IGFBP-5 that is made by fibroblasts appears to be
      sequestered by epithelial cells. IGFBP-5 may, therefore, be a factor in cellular
      interactions between stromal and epithelial cells that are of fundamental
      importance for normal prostatic development and function.

PMID- 8855839
TI  - Ectopic production of intact parathyroid hormone by a squamous cell lung
      carcinoma in vivo and in vitro.
AB  - Ectopic tumoral production of intact parathyroid hormone (PTH) is rare. The PTH
      related protein is the common cause of hypercalcemia in most solid tumors,
      particularly squamous and renal carcinomas. We report the case of a 71-yr-old man
      with a PTH-producing squamous cell lung carcinoma. Immunocytochemical analysis of
      the tumor tissue as well as of cultured tumor cells revealed PTH positive
      staining. Cultured tumor cells released PTH and were calcium sensitive, producing
      122 +/- 16 pg/microgram DNA of intact PTH (mean +/- SEM) at 0.5 mmol/L calcium
      compared with 26 +/- 2 pg/microgram DNA at 3.0 mmol/L calcium. Somatostatin
      analogues have been used in the treatment of humoral hypercalcemia of malignancy
      (HHM). However, we found that somatostatin (0.1 microgram/L) in cultured tumor
      cells increased the release of intact PTH (123 +/- 19 versus 82 +/- 1
      pg/microgram DNA, P < 0.05) and thus might have a negative effect on the HHM.
      This report is the first to describe a true ectopic PTH-producing squamous cell
      lung carcinoma associated with HHM.

PMID- 8855840
TI  - Mutation of cytochrome P-45017 alpha gene (CYP17) in a Japanese patient
      previously reported as having glucocorticoid-responsive hyperaldosteronism: with
      a review of Japanese patients with mutations of CYP17.
AB  - A 17-yr-old female Japanese patient, who was reported in 1968 as having
      glucocorticoid-responsive hyperaldosteronism but was presumed to have a defect of
      17 alpha-hydroxylation mainly in the adrenal glands as the etiology of her
      illness, was followed. The relationship between clinical manifestations and
      molecular abnormalities in cytochrome P-45017 alpha gene (CYP17) was also
      reviewed based on the literature on Japanese patients with 17 alpha-hydroxylase
      deficiency. She has been treated with dexamethasone, resulting in normal blood
      pressure and normokalemia for 28 yr. She had almost normal gonadal function with
      regular menstruation on her first admission. Because of sustained genital
      bleeding, however, she underwent total hysterectomy with an ovarian biopsy at the
      age of 42 yr. No follicles or corpus luteum were detected in the ovarian
      specimen. At the age of 45 yr, the basal levels of sex steroids were decreased,
      while those of gonadotropins were increased. A genetic study on CYP17 revealed a
      homozygous deletion of phenylalanine (Phe) codon (TTC) at either amino acid
      position 53 or 54 in exon 1. A review of the literature revealed 4 patients with
      this type of CYP17 mutation, including the present patient, out of a total of 11
      young adult Japanese patients. The clinical manifestations caused by congenitally
      deficient gonadal function were not marked in any of these 4 patients, but were
      marked in 5 of the 7 patients with different mutations of CYP17. The remaining 2
      female patients had irregular menstruation. The pretreatment urine/plasma values
      of aldosterone were variable, normal to high, in individual patients, regardless
      of the structural abnormalities of CYP17. The following conclusions were
      suggested: 1) this type of CYP17 mutation is associated with well preserved
      gonadal function in young adult patients, but it likely causes early reduction of
      gonadal function with increasing age in these patients; 2) the prevalence of this
      type of CYP17 mutation is quite high in Japanese patients; and 3) the
      pretreatment hyperaldosteronism observed in the present patient seems not to be
      related to the mutation of CYP17.

PMID- 8855841
TI  - Response to challenge with gonadotropin-releasing hormone agonist in a mother and
      her two sons with a constitutively activating mutation of the luteinizing hormone
      receptor--a clinical research center study.
AB  - The pituitary-gonadal axis was evaluated in a mother after two of her sons with
      familial male-limited pseudoprecocious puberty were found to have a
      constitutively activating mutation of the LH receptor (LHR). Genotyping
      demonstrated that all showed a mutation in one of the two alleles, a substitution
      of Gly for Asp578 in the sixth transmembrane segment of the LHR. Ovarian function
      was normal in the 36-yr-old mother as assessed by LH dynamics and FSH and
      androgen levels throughout the menstrual cycle. Hormonal responses to acute GnRH
      agonist (nafarelin) challenge, chronic GnRH agonist administration, and
      dexamethasone were also normal. Studies of the boys upon presentation at 2.4 and
      3.5 yr of age revealed that acute LH responses to nafarelin were in the
      hypogonadotropic range, and the FSH responses were prepubertal despite the
      presence of late pubertal testosterone blood levels. Upon the inception of true
      puberty at 11 yr of age in the older brother, gonadotropin responses normalized
      for the state of development. The data show that this activating LHR mutation
      does not cause functional ovarian hyperandrogenism and causes only incomplete
      pubertal activation of Leydig cells. The results are compatible with relatively
      low constitutive activity associated with this structural abnormality of LHR.

PMID- 8855842
TI  - Human placenta and fetal membranes express human urocortin mRNA and peptide.
AB  - Recently a new member of the corticotropin-releasing factor (CRF) family has been
      cloned and named urocortin. It has been localized in rat brain and to human
      chromosome 2. The present study investigated whether human placenta and related
      tissues express mRNA and immunoreactive urocortin. Using specific oligonucleotide
      primers, reverse transcriptase-polymerase chain reaction experiments were
      performed on total RNA isolated from human placenta and decidua collected both at
      early stage of gestation (8-11 weeks) and at term (39-40 weeks). In addition,
      experiments were also done on specimens of amnion and chorion collected at term.
      Independently from the gestational age, placental and decidual cells expressed
      urocortin mRNA, with a 145 bp DNA band corresponding to the expected length. The
      expression of urocortin mRNA was also found in amnion and chorion. Using specific
      antiserum and an immunoperoxidase technique, immunoreactive urocortin was then
      localized in syncytiotrophoblast cells and in some extent in cytotrophoblast
      cells of placental villi at term, as well as in fetal membranes and maternal
      decidua. The present findings revealed that human placenta and gestational
      related tissues express human urocortin gene and localize immunoreactive
      urocortin, supporting the concept that these tissues are capable of expressing a
      large number of neuroendocrine peptides.

PMID- 8855843
TI  - Steroid secretions in patients with adrenal incidentalomas.

PMID- 8855844
TI  - A longitudinal evaluation of bone mineral density in adult men with histories of
      delayed puberty.

PMID- 8855845
TI  - Frustrating survey of chronic fatigue.

PMID- 8855846
TI  - Risk of venous thrombosis with hormone-replacement therapy.

PMID- 8855847
TI  - Can iron supplementation improve cognitive functioning?

PMID- 8855848
TI  - Interferon therapy for hepatitis C.

PMID- 8855849
TI  - Application of image-based brain analysis to research and clinical problems.

PMID- 8855850
TI  - Antenatal phenobarbitone and neonatal outcome.

PMID- 8855851
TI  - Cairo dreams shattered.

PMID- 8855852
TI  - Risk of venous thromboembolism in users of hormone replacement therapy.
AB  - BACKGROUND: The association between current use of oral contraceptives and
      increased risk of venous thromboembolism (VTE) has been firmly established.
      Although data-sheets for hormone replacement therapy (HRT) carry similar warnings
      as regards VTE, evidence of an association is inconclusive. We carried out a
      hospital-based case-control study to investigate whether current use of HRT is
      associated with VTE. METHODS: We screened all women aged 45-64 years admitted to
      hospitals in the area of the Oxford Regional Health Authority with a suspected
      diagnosis of VTE between February, 1993, and December, 1994. We recruited 81
      cases of idiopathic VTE and 146 hospital controls with disorders of eyes, skin,
      ears, respiratory and alimentary tracts, kidneys, bones, and joints, and trauma;
      controls were matched to cases for age-group and date and district of admission.
      To increase the study power, an additional 22 cases of idiopathic VTE and 32
      hospital controls admitted before February, 1993, were recruited retrospectively.
      Participants were questioned about medical and gynaecological history, use of
      oral contraceptives and HRT, use of other drugs within the previous 3 months, and
      lifestyle and socioeconomic characteristics. Detailed diagnostic data were
      extracted from the notes of eligible cases. Matched analyses, adjusted for body
      mass Index, socioeconomic group, and history of varicose veins, were undertaken
      by conditional logistic regression. FINDINGS: 44 (42.7%) cases and 44 (24.7%)
      controls were current users of HRT. The adjusted odds ratio for VTE in current
      users of HRT compared with non-users (never-users and past users combined) was
      3.5 (95% CI 1.8-7.0; p < 0.001). No association was found with past use, and risk
      appeared to be highest among short-term current users (adjusted likelihood ratio
      test of trend in odds ratios across different durations of current use, p =
      0.011). INTERPRETATION: Current HRT use is associated with risk of VTE. The
      increased risk may be concentrated in new users. The number of extra cases
      appears to be only about one in 5000 users per year. These findings need to be
      weighed against the probable benefits of long-term treatment, including
      reductions in risks of osteoporotic fracture and coronary heart disease, and the
      probable modest increase in risk of breast cancer.

PMID- 8855853
TI  - Risk of hospital admission for idiopathic venous thromboembolism among users of
      postmenopausal oestrogens.
AB  - BACKGROUND: At the request of researchers in the UK, we conducted a case-control
      study to explore the relation between use of postmenopausal oestrogen hormone
      replacement therapy (HRT) and idiopathic venous thromboembolism (VTE). METHODS:
      The study was based on information derived from Group Health Cooperative of Puget
      Sound for the period 1980 to 1994. Women aged 50-74 years admitted to hospital
      for idiopathic VTE were identified from hospital records. The diagnosis of
      idiopathic VTE was validated from the clinical record. Women who had medical
      conditions predisposing to VTE (a history of VTE or cancer, recent trauma, or
      surgery) were excluded as cases. Four control subjects matched to each case by
      age, duration of Cooperative membership, and calendar time were identified from
      the base population. Various potential risk factors were recorded based on record
      review. FINDINGS: An initial analysis of 42 cases and 168 matched controls
      yielded a matched relative risk estimate of 3.6 (95% CI 1.6-7.8) for current
      users of oestrogens compared with non-users. There was a substantial effect of
      daily oestrogen dose. The matched relative risk estimates for oestrogen users of
      0.325 mg, 0.625 mg, and 1.25 mg or more daily were 2.1, 3.3, and 6.9,
      respectively. Body-mass index was independently associated with the risk of VTE
      but did not materially confound the relation of oestrogen and VTE. The absolute
      risk of idiopathic VTE is estimated to be low (0.9 x 10(-4) woman-years) in non
      users of oestrogen; the risk in current users is estimated at 3.2 x 10(-4) woman
      years. INTERPRETATION: The risk of idiopathic VTE is about three times higher
      among current users of replacement oestrogens than among non-users. However, the
      absolute risk is low for both groups and accounts for only a modest increase in
      morbidity.

PMID- 8855854
TI  - Prospective study of exogenous hormones and risk of pulmonary embolism in women.
AB  - BACKGROUND: Current use of oral contraceptives (OCs) is a well-recognised risk
      factor for venous thrombosis and consequent pulmonary embolism (PE). Little is
      known about residual effects of past OC use. Furthermore, few epidemiological
      studies have assessed the relation between postmenopausal use of hormones and
      thrombotic disease. METHODS: In this prospective study information was obtained
      through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55
      in 1976. We excluded women with previously diagnosed cardiovascular disease or
      cancer in 1976 and at the beginning of each subsequent 2-year follow-up period.
      FINDINGS: From self-reports and medical records, we documented 123 cases of
      primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation).
      Current users of postmenopausal hormones had an increased risk of primary PE
      (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However,
      past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the
      risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this
      finding was based on only five cases who were current OC users. Users of OCs in
      the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were
      consistent irrespective of cigarette-smoking status. INTERPRETATION: Primary PE
      was uncommon in this cohort. The risk was increased by current though not past
      use of postmenopausal hormones or OCs.

PMID- 8855855
TI  - HIV incidence among injecting drug users in New York City syringe-exchange
      programmes.
AB  - BACKGROUND: There have been no studies showing that participation in programmes
      which provide legal access to drug-injection equipment leads to individual-level
      protection against incident HIV infection. We have compared HIV incidence among
      injecting drug users participating in syringe-exchange programmes in New York
      City with that among non-participants. METHODS: We used meta-analytic techniques
      to combine HIV incidence data from injecting drug users in three studies: the
      Syringe Exchange Evaluation (n = 280), in which multiple interviews and saliva
      samples were collected from participants at exchange sites; the Vaccine
      Preparedness initiative cohort (n = 133 continuing exchanges and 188 non
      exchangers, in which participants were interviewed and tested for HIV every 3
      months; and very-high-seroprevalence cities in the National AIDS Demonstration
      Research (NADR) programme (n = 1029), in which street-recruited individuals were
      interviewed and tested for HIV every 6 months. In practice, participants in the
      NADR study had not used syringe exchanges. FINDINGS: HIV incidence among
      continuing exchange-users in the Syringe Exchange Evaluation was 1.58 per 100
      person-years at risk (95% CI 0.54, 4.65) and among continuing exchange-users in
      the Vaccine Preparedness Initiative it was 1.38 per 100 person-years at risk
      (0.23, 4.57). Incidence among non-users of the exchange in the Vaccine
      Preparedness Initiative was 5.26 per 100 person-years at risk (2.41, 11.49), and
      in the NADR cities, 6.23 per 100 person-years at risk (4.4, 8.6). In a pooled
      data, multivariate proportional-hazards analysis, not using the exchanges was
      associated with a hazard ratio of 3.35 (95% CI 1.29, 8.65) for incident HIV
      infection compared with using the exchanges. INTERPRETATION: We observed an
      individual-level protective effect against HIV infection associated with
      participation in a syringe-exchange programme. Sterile injection equipment should
      be legally provided to reduce the risk of HIV infection in persons who inject
      illicit drugs.

PMID- 8855856
TI  - Randomised study of cognitive effects of iron supplementation in non-anaemic iron
      deficient adolescent girls.
AB  - BACKGROUND: Up to 25% of adolescent girls in the USA are iron deficient. This
      double-blind, placebo-controlled clinical trial assessed the effects of iron
      supplementation on cognitive function in adolescent girls with non-anaemic iron
      deficiency. METHODS: 716 girls who enrolled at four Baltimore high schools were
      screened for non-anaemic iron deficiency (serum ferritin < or = 12 micrograms/L
      with normal haemoglobin). 98 (13.7%) girls had non-anaemic iron deficiency of
      whom 81 were enrolled in the trial. Participants were randomly assigned oral
      ferrous sulphate (650 mg twice daily) or placebo for 8 weeks. The effect of iron
      treatment was assessed by questionnaires and haematological and cognitive tests,
      which were done before treatment started and repeated after the intervention. We
      used four tests of attention and memory to measure cognitive functioning.
      Intention-to-treat and per-protocol analyses were done. FINDINGS: Of the 81
      enrolled girls with non-anaemic iron deficiency, 78 (96%) completed the study (39
      in each group). Five girls (three control, two treatment) developed anaemia
      during the intervention and were excluded from the analyses. Thus, 73 girls were
      included in the per-protocol analysis. Ethnic distribution, mean age, serum
      ferritin concentrations, haemoglobin concentrations, and cognitive test scores of
      the groups did not differ significantly at baseline. Postintervention
      haematological measures of iron status were significantly improved in the
      treatment group (serum ferritin 27.3 vs 12.1 micrograms/L, p < 0.001). Regression
      analysis showed that girls who received iron performed better on a test of verbal
      learning and memory than girls in the control group (p < 0.02). INTERPRETATION:
      In this urban population of non-anaemic iron-deficient adolescent girls, iron
      supplementation improved verbal learning and memory.

PMID- 8855857
TI  - Breast-duct endoscopy to study stages of cancerous breast disease.
AB  - BACKGROUND: In breast-cancer research, we lack reproducible non-invasive access
      to breast tissue. Breast cancer is thought to start in the lining of the milk
      duct or lobule. We have had no direct access to this area other than in tissue
      removed surgically or by fine-needle aspiration. Our objective was to explore an
      intraductal approach to studying breast cancer and precancerous changes by duct
      cannulation and endoscopy. METHODS: In this pilot study, women in a university
      hospital were asked to participate. Nine patients with previously diagnosed
      ductal carcinoma-in-situ (DCIS) or invasive breast cancer who were about to
      undergo mastectomy under general anaesthesia agreed. After the patient was asleep
      but before the operation, we spent 15 minutes cannulating their ducts, obtaining
      washings, and attempting endoscopy. The ducts that had been cannulated were
      marked by instillation of dye or other materials, the nipple was sutured shut,
      and the mastectomy proceeded as planned. The mastectomy specimen underwent
      extensive histopathological examination. FINDINGS: We were successful in
      intraductal cannulation and endoscopy in seven of the nine patients. In five of
      the nine, we obtained epithelial cells in the washings. In one the cells were
      consistent with proliferative disease, in three there was atypical epithelium,
      and in one there was frank DCIS. With several different contrast materials
      injected into separate duct orifices, DCIS was confined to a single duct system.
      INTERPRETATION: We found that the intraductal approach is feasible for the study
      of the early changes of breast cancer Technical difficulties include
      identification of the breast duct orifices, determining the distensibility of the
      duct, and developing a reliable technique to obtain washings.

PMID- 8855858
TI  - An emotional 13-year-old girl.

PMID- 8855859
TI  - The health care system evolves.

PMID- 8855860
TI  - Biomedical research in an era of unlimited aspirations and limited resources.

PMID- 8855861
TI  - Managed care and medical education.

PMID- 8855862
TI  - Academic institutions and primary care.

PMID- 8855863
TI  - Practice guidelines: to be or not to be.

PMID- 8855864
TI  - The federal role in health technology assessment.

PMID- 8855865
TI  - Medicine and HIV. Interview by David Frankel.

PMID- 8855866
TI  - Public health and urban medicine.

PMID- 8855867
TI  - Low-efficacy HIV vaccines: potential for community-based intervention programmes.
AB  - To combat the spread of HIV, progress on vaccine development is eagerly awaited.
      Haynes in this series has described the progress made so far with various vaccine
      types. This article describes how mathematical modelling techniques can be used
      to predict the likely impact of low-efficacy vaccines in community transmission
      of the virus. The answers are often not what one would predict by intuition
      alone, and they have great bearing on the likely success of such vaccination
      strategies.

PMID- 8855868
TI  - Literature and medicine: some major works.

PMID- 8855869
TI  - Case-control study of venous thromboembolism risk in users of hormone replacement
      therapy.

PMID- 8855870
TI  - Oestrogen and Alzheimer's disease.

PMID- 8855871
TI  - Oestrogen and Alzheimer's disease.

PMID- 8855872
TI  - Oestrogen and Alzheimer's disease.

PMID- 8855873
TI  - Oestrogen and Alzheimer's disease.

PMID- 8855874
TI  - Oestrogen and Alzheimer's disease.

PMID- 8855875
TI  - Oral rehydration solutions.

PMID- 8855876
TI  - Oesophageal stricture associated with alendronic acid.

PMID- 8855877
TI  - Ticlopidine and renal function.

PMID- 8855878
TI  - Ticlopidine and renal function.

PMID- 8855879
TI  - HGV in coagulation-factor concentrates.

PMID- 8855880
TI  - GBV-C/HGV infection and aplastic anaemia.

PMID- 8855881
TI  - Intracerebral haemorrhage after contact with Lonomia caterpillars.

PMID- 8855882
TI  - Risks with citalopram in perspective.

PMID- 8855883
TI  - Fictitious breast cancer family history.

PMID- 8855884
TI  - Performance of Indian medical colleges.

PMID- 8855885
TI  - Combating abuses in high-level adolescent sport.

PMID- 8855886
TI  - Thrombolysis after stroke.

PMID- 8855887
TI  - PCBs and HCB in serum of full-term German neonates.

PMID- 8855888
TI  - Methaemoglobinaemia after inhalation of nitric oxide for treatment of
      hydrochlorothiazide-induced pulmonary oedema.

PMID- 8855889
TI  - Preoperative testing for HIV: a survey of surgeons' attitudes and practices.

PMID- 8855890
TI  - Gastrointestinal manifestations of HIV infection.

PMID- 8855891
TI  - Methylenetetrahydrofolate reductase mutation and neural tube defects.

PMID- 8855892
TI  - Endoscopic ligation of gastric varices.

PMID- 8855893
TI  - Vancomycin-resistant enterococci in cats and dogs.

PMID- 8855894
TI  - Mycotoxins in myelopathies of man.

PMID- 8855895
TI  - Sheffield risk and treatment table for primary prevention of coronary heart
      disease.

PMID- 8855896
TI  - Sheffield risk and treatment table for primary prevention of coronary heart
      disease.

PMID- 8855897
TI  - Lamotrigine and toxic epidermal necrolysis.

PMID- 8855898
TI  - Regression of MALT lymphoma and treatment for Helicobacter pylori.

PMID- 8855900
TI  - Setting the record straight on hospital RNs.

PMID- 8855899
TI  - Horn playing and blood pressure.

PMID- 8855901
TI  - RN support seen for assisted suicide.

PMID- 8855902
TI  - Starting recovery.

PMID- 8855903
TI  - Managing urinary tract infections. Part 1: diagnosing and treating adults.

PMID- 8855904
TI  - Preparing for nursing's future.

PMID- 8855905
TI  - A care plan for living.

PMID- 8855906
TI  - Avoiding adverse reactions.

PMID- 8855907
TI  - PCA: for patients only.

PMID- 8855908
TI  - Complications of MI: beyond the acute stage.

PMID- 8855909
TI  - Six tips for caring for aging parents.

PMID- 8855910
TI  - Back to basics: choosing the correct wound dressing.

PMID- 8855911
TI  - Clinical snapshot: kidney stones.

PMID- 8855912
TI  - Delegation are you doing it right?

PMID- 8855913
TI  - Emergency! Sickle cell crisis.

PMID- 8855914
TI  - Visions of those who left too soon.

PMID- 8855915
TI  - A secret too big to keep.

PMID- 8855916
TI  - Saving the unseen patient.

PMID- 8855917
TI  - Internet and surgery.
AB  - In medicine, the Internet is already playing a significant role in the delivery
      of information on medical conditions, medical and academic institutions and non
      profit-making support groups for patients. This article explores some of the
      available information on the Internet relevant to surgery and discusses its role
      in surgical training.

PMID- 8855918
TI  - Trauma admissions in the southern highlands of Papua New Guinea.
AB  - BACKGROUND: Trauma is a common cause of surgical admission in Papua New Guinea
      (PNG) but to date there has been no study of the whole trauma burden in
      provincial hospitals. METHODS: A 1-year retrospective study was made of all
      surgical admissions to the provincial hospital at Mendi. RESULTS: Trauma was the
      third commonest reason for hospital admission and accounted for 43% of all
      surgical cases. The common causes of injury were tribal fights (24%), domestic
      violence (14.3%), assault (16.7%), road accidents (14%) and domestic accidents
      (25.1%), which comprised falls, penetrating wounds and bites. Males accounted for
      two-thirds of cases, and 19% were children below the age of 16. Only eight of 454
      patients died (1.8%), because most trauma deaths occur before the patient reaches
      hospital. There were only 37 multiple injuries and only five patients had an
      injury severity score of greater than 16. The average inpatient stay for trauma
      admissions was 10.6 days. CONCLUSIONS: The cost of trauma in Mendi is difficult
      to calculate, but is enormous. In addition to 11% of the recurrent hospital
      expenditure (over US$1.1 million, excluding pharmaceuticals), the community costs
      include loss of earnings and productivity, as well as permanent disability. The
      social disruption caused by tribal fights results in cessation of the local
      economy, burning of aid posts, schools and homes and destruction of gardens for
      subsistence farming. Those who reach hospital alive tend to have single injuries
      and survive.

PMID- 8855919
TI  - The role of core biopsy in the diagnosis of mammographically detected lesions.
AB  - BACKGROUND: Both stereotactic imaging and ultrasound have been used to localize
      non-palpable breast lesions for core biopsy analysis. In particular, stereotactic
      core breast biopsy with a dedicated recumbent mammographic unit is an accurate
      and reliable technique, and this has been substantiated in a number of recent
      prospective studies comparing percutaneous core biopsy with open excisional
      biopsy. METHODS: This article reviews biopsies of 521 lesions from 502 cases
      using both stereotactic localization (469 lesions) and ultrasound (33 lesions).
      The types of breast cancer and benign breast disease diagnosed with core sampling
      are reviewed. In this series it was not intended to compare all the results of
      core biopsies with those of open excisional biopsy, but a subset group, which
      comprised certain benign lesions and malignancies, as well as lesions diagnosed
      on core biopsy in which the radiology and pathology did not correlate, was
      further evaluated and compared to the findings with open biopsy. The cases where
      there were differences in core and excisional biopsy diagnosis are discussed.
      RESULTS: In this series the benign to malignant ratio was 2.7:1, in other words,
      27% of the lesions biopsied were malignant. The sensitivity for detecting cancer
      was 97% with the positive predictive value being 99%. CONCLUSIONS: This series
      further substantiates the accuracy of core biopsy. It is recommended that certain
      lesions diagnosed as benign on core biopsy histology should also proceed to open
      biopsy. Correlation between clinical findings, radiology and pathology further
      improves the reliability of core biopsy under imaging guidance.

PMID- 8855920
TI  - Enteral versus parenteral nutrition after oesophagogastric surgery: a prospective
      randomized comparison.
AB  - BACKGROUND: There appears to be an emerging consensus that early postoperative
      nutritional support benefits the high-risk patient by decreasing septic
      morbidity, maintaining immunocompetence and improving wound healing. Enteral
      nutrition via a feeding jejunostomy has been associated with serious
      complications, with a reported mortality rate as high as 10%, while total
      parenteral nutrition has also been associated with a wide variety of
      complications. METHODS: Ninety-seven patients undergoing oesophagectomy or
      gastrectomy underwent pre-operative nutritional assessment and were randomized to
      receive either total parenteral nutrition (47 patients) or enteral nutrition (50
      patients). RESULTS: There was no significant difference in the number of catheter
      related complications between the two groups, but 9 (45%) patients in the total
      parenteral nutrition group had major morbidity (potentially fatal in two
      patients) requiring active intervention. CONCLUSIONS: This study demonstrates
      enteral nutrition to be safe and associated with mainly reversible minor
      complications. It is probable that immediate postoperative enteral feeding
      conserves the gut's integrity. Whether this leads to a reduction in postoperative
      septic complications has not been demonstrated by this study although there
      appears to be a trend in this direction, supporting the concept of enteral
      feeding as 'primary therapy'. This can be safely, simply and economically
      achieved using a feeding jejunostomy placed at the time of surgery.

PMID- 8855921
TI  - A comparison of reusable versus disposable laparoscopic instrument costs.
AB  - BACKGROUND: Between 1991 and 1993 a single set of reusable laparoscopic
      instruments was used to perform 404 cholecystectomies, 102 hernia repairs and 66
      advanced procedures. Disposable instruments were used only when no suitable
      reusable instrument was available or when reusable instruments were not working
      to the satisfaction of the surgeon. METHODS: The cost of performing those
      laparoscopic operations using this policy was calculated by adding the purchase
      cost, the maintenance costs and the repair and replacement costs of the reusable
      instruments. To this figure was added the cost of disposable instruments which
      were used instead of reusable instruments during the study period. RESULTS: The
      total cost was $253,385, at an average of $443 per case. The cost per case for
      reusable instruments remained approximately $100 through the 3 years, while the
      cost per case of disposable instruments fell from almost $600 in 1991 to about
      $200 in 1993. CONCLUSIONS: Our future policy is to continue using reusable
      instruments initially, with backup disposable instruments.

PMID- 8855922
TI  - Surgical considerations in the Hartmann's procedure.
AB  - BACKGROUND: The present study examines the surgical outcome of the Hartmann's and
      Hartmann-type procedures, the problems with the remnant rectal stump and the
      issues related to the colorectal anastomosis as well as the differences in
      patient outcome. METHODS: One hundred and five consecutive patients (mean age 66)
      were evaluated. Surgical morbidity and mortality were analysed with regard to the
      colorectal pathology and the type of rectal stump remnant. The surviving patients
      were reviewed according to whether they had second-stage anastomosis. RESULTS: In
      65% of cases there were obstructed or perforated malignancies and in 16%
      complicated diverticular diseases. The peri-operative mortality and morbidity
      were 11.4% and 24%, respectively. Seventy-two patients had intraperitoneal rectal
      stumps and stump blowout occurred in three intraperitoneal and one
      extraperitoneal remnant stumps. Local tumour recurrence (four) and diversion
      proctitis (three) were diagnosed in the rectal stump among asymptomatic patients.
      When the second-stage reversal of Hartmann's procedure was considered (35 cases),
      twice as many were performed for diverticular and other benign conditions as for
      tumour cases. CONCLUSIONS: Although there is a good anatomical basis for
      advocating extraperitoneal rather than intraperitoneal stumps, in practice the
      stump blowout rate is not statistically significant (3% vs 4.1%). However, the
      chances of regaining normal rectal function are much better for benign disease
      (68% vs 32%--Fisher's exact test, P = 0.004). Complications from second-stage re
      anastomosis are not determined by timing of the closure, provided the septic
      episode has subsided.

PMID- 8855923
TI  - The development of a treatment protocol for patients with chronic radiation
      induced rectal bleeding.
AB  - BACKGROUNDS AND METHODS: This study reviews the clinical features and reports the
      preliminary results of treatment of 34 consecutive patients with clinically
      significant bleeding from chronic, radiation-induced proctitis, using a
      combination of endoscopic YAG Laser and the application of topical formalin
      dressings to the rectal mucosa. RESULTS: Bleeding ceased in 25 patients (74%);
      bleeding continued but occurred only slightly and occasionally in five patients
      (15%); and three patients required operation to control the bleeding (9%). One
      patient relapsed after treatment and died while receiving a further transfusion.
      CONCLUSIONS: This experience has been used to develop a management protocol for
      patients with this serious complication.

PMID- 8855924
TI  - Suspected intussusception: is ultrasound a reliable diagnostic aid?
AB  - BACKGROUND: Infantile intussusception often presents with symptoms more common to
      less dangerous conditions, and diagnosis must be established as early as
      possible. Clinical diagnosis is often wrong and contrast enema is invasive.
      Sonography is painless and harmless and if it provides a reliable method of
      diagnosis or exclusion of intussusception, diagnostic delay will be avoided.
      METHODS: In the John Hunter Hospital, Newcastle, between 1993 and 1994, the names
      of all children referred for abdominal sonography with a degree of suspicion of
      intussusception were recorded, and the histories were subsequently reviewed.
      RESULTS: Fifty patients were studied. Forty-one patients had no sonographic
      evidence of intussusception and nine patients had positive findings. None of the
      41 patients who had negative sonograms proved to have intussusception. The nine
      patients who had positive findings were subjected to air enema. In two patients
      the sonographic diagnosis was proved wrong. In the other seven patients it was
      confirmed. Thus there were two false positives and no false negatives.
      CONCLUSION: Sonography is a reliable aid to the clinical diagnosis of
      intussusception.

PMID- 8855925
TI  - Treatment principles in advanced non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) accounts for more than three quarters of all
      lung tumours and is the leading cause of deaths due to cancer in Australia. More
      than half of the patients with NSCLC present with advanced disease. Radiation
      therapy has been the mainstay of active treatment for these patients. There is
      increasing evidence supporting the benefit of chemotherapy as an addition to
      radiation therapy in locally advanced non-metastatic disease. The use of
      cisplatin-based chemotherapy prior to radiation therapy would appear to be a new
      standard of care in patients with stage III B NSCLC. In advanced (metastic)
      disease, palliation of symptoms remains the major goal of current treatment
      programmes. This can be achieved with the best supportive care, radiotherapy,
      and, in selected patients, platinum-based chemotherapy. Clinical trials to test
      new treatments, with survival, quality of life and cost-benefit as endpoints, are
      essential. The present study discusses the current status of conventional and
      newer treatment methods in locally advanced and metastatic disease.

PMID- 8855926
TI  - Bizarre parosteal osteochondromatous proliferation: a review of seven cases.
AB  - BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare
      tumour-like condition mostly affecting the tubular bones of the hands and feet.
      Although it recurs in 50% of cases after local excision, it is a form of
      heterotopic ossification and its behaviour is otherwise benign. The present study
      describes seven cases of BPOP collected by the Bone Tumour Registry of New South
      Wales. METHODS: Clinical data, radiographs and histological specimens collected
      by the Bone Tumour Registry of New South Wales were examined, and further
      clinical data were sought from the referring doctor where necessary. RESULTS: Six
      males and one female aged 18 to 37 years (median 30 years) presented between 1988
      and 1995. There were three cases involving the hands, three involving the feet
      and one involving the distal humerus. Initial treatment was by local excision in
      all cases. There was local recurrence in three cases. The initial diagnosis was
      wrong in five of the seven cases. Radiologically, BPOP appears as a well-defined
      tumour arising directly from the bony cortex, without periosteal reaction or
      change to the underlying bone. Histologically, a large amount of hypercellular
      cartilage shows maturation to trabecular bone, which frequently contains spindle
      cells in the intertrabecular spaces. CONCLUSION: BPOP is a rare, locally
      recurrent but otherwise benign condition of bone which must be distinguished from
      more sinister lesions such as parosteal osteosarcoma and chondrosarcoma.

PMID- 8855927
TI  - The new age of liver transplantation.
AB  - The advent of cyclosporin A for immunosuppression (IS) in liver transplantation
      (LTx) in the early 1980s heralded a new age for LTx, resulting in widespread
      application, rapidly expanding indications, relaxation of restrictions in donor
      selection and advances in the preservation of liver grafts and management of LTx
      operations. Liver transplantation, together with the transplantation of other
      organs (kidney, pancreas, heart, heart-lung, intestine), became possible. In
      Australia, around 125 LTx (22% in children) are performed each year. Indications
      are: primary sclerosing cholangitis; primary biliary cirrhosis; auto-immune
      hepatitis; chronic viral hepatitis; biliary atresia; metabolic disorders;
      fulminant hepatic failure (FHF); alcoholic cirrhosis; and malignancy (cancer,
      CA). Since 1965, 810 patients underwent LTx and 70 (9%) re-Tx. Patient survivals
      at 1, 5 and 9 years post-Tx are 80, 74 and 66%, respectively. Patients with
      primary diseases that recur in the LTx (hepatitis B and CA) do less well
      following LTx, with 5-year survival rates of 55 and 40%, respectively). Recent
      developments include: increasing the availability of donor organs by the use of
      living donors, 'split' cadaveric donor (CD) grafts, 'marginal' and non-heart
      beating CD grafts and xenografts; expanding the indications for LTx; development
      of effective liver support systems for patients with FHF; the treatment of
      diabetics with liver failure with islet Tx (at the time of LTx); more effective
      immunosuppression; and methods to diminish recurrent disease in LTx. Some
      understanding of the unique 'tolerogenic' capabilities of the liver has come with
      the recognition of 'two-way microchimerism'. The satisfactory 5-9 year outcomes
      for patients underline the cost-effectiveness of LTx.

PMID- 8855928
TI  - Ischaemic preconditioning of the liver: a preliminary study.
AB  - BACKGROUND: A phenomenon of 'preconditioning' exists for the heart, but has not
      been described for the liver. This study was undertaken to determine whether a
      brief episode of ischaemia (3 or 5 min) followed by a short reperfusion time (5
      or 10 min) would precondition the liver to reduce subsequent injury from
      prolonged ischaemia (30 to 90 min). METHODS: Male Wistar rats were allocated into
      five control (no preconditioning) and five preconditioned groups, each having a
      liver resection. The preconditioning times were 3 min ischaemia followed by 5 min
      reperfusion with a prolonged ischaemia of 60 or 90 min for the first two groups,
      and 5 min ischaemia followed by 10 min reperfusion with prolonged ischaemia times
      of 30 or 45 min for the other three groups. RESULTS: Of rats resected with 3-5-60
      min time sequence designed to assess survival, 9/10 died. However 9/10 died also
      in the matching control group with 60 min ischaemia. With a 5-10-45 min sequence,
      9/10 survived more than 24 h in the preconditioned group and 1/10 in the non
      preconditioned controls. With a 5-10-30+ sequence designed to measure liver
      function tests, the prothrombin time was significantly improved; bilirubin, serum
      alkaline phosphatase and the alanine aminotransferase improved but these did not
      reach significance. CONCLUSION: A brief episode of ischaemia followed by an
      episode of reperfusion before a prolonged period of ischaemia ameliorated the
      effects of ischaemia-reperfusion injury in a rat liver resection model. If
      hepatic preconditioning is confirmed in humans, ischaemic preconditioning will
      have an important role for all liver surgery.

PMID- 8855929
TI  - Pneumothorax during laparoscopic mobilization of the oesophagus.
AB  - During laparoscopic dissection of the oesophagus, the left pleura is easily
      breached, resulting in pneumothorax. This complication has not been widely
      reported, although it is likely to be common. Management depends on subsequent
      cardiorespiratory effects, which are variable. Five cases are reported from an
      initial experience of 190 laparoscopic Nissen fundoplications, illustrating a
      variety of presentations and management options.

PMID- 8855930
TI  - Solitary gastric Peutz-Jeghers polyp and angiolipoma presenting as acute
      haemorrhage.

PMID- 8855931
TI  - Control of pre-sacral haemorrhage by drawing pin tamponade.

PMID- 8855932
TI  - Congenital posterior urethral diverticulum.

PMID- 8855933
TI  - Folding intermediates of a beta-barrel membrane protein. Kinetic evidence for a
      multi-step membrane insertion mechanism.
AB  - The mechanism of folding and membrane insertion of integral membrane proteins,
      including helix bundle and beta-barrel proteins is not well understood. A key
      question is whether folding and insertion are coupled or separable processes. We
      have used the beta-barrel outer membrane protein A (OmpA) of Escherichia coli as
      a model to study the kinetics of folding and insertion into
      dioleoylphosphatidylcholine (DOPC) bilayers, as a function of temperature by gel
      electrophoresis, protease digestion, and fluorescence spectroscopy. OmpA was
      unfolded in 8 M urea solution (without detergent), and refolding and membrane
      insertion was initiated by rapid dilution of the urea concentration in the
      presence of phospholipid vesicles. In addition to the kinetically unresolved
      hydrophobic collapse in water, the time course of refolding of OmpA into DOPC
      bilayers exhibited three kinetic phases over a large temperature range. The first
      step was fast (k1 = 0.16 min-1) and not very dependent on temperature. The second
      step was up to two orders of magnitude slower at low temperatures (2 degrees C),
      but approached the rate of the first step at higher temperatures (40 degrees C).
      The activation energy for this process was 46 +/- 4 kJ/mol. A third slow process
      (k3 = 0.9 x 10(-2) min-1 at 40 degrees C) was observed at the higher
      temperatures. These results suggest that at least two membrane-bound
      intermediates exist when OmpA folds and inserts into lipid bilayers. We also show
      that both membrane-bound intermediates can be stabilized in fluid lipid bilayers
      at low temperatures. These intermediates share many properties with the
      adsorbed/partially inserted form of OmpA that was previously characterized in gel
      phase lipid bilayers [Rodionova et al. (1995) Biochemistry 34, 1921-1929].
      Temperature jump experiments demonstrate, that the low-temperature intermediates
      can be rapidly converted to fully inserted native OmpA. On the basis of these and
      previous results, we present a simple folding model for beta-barrel membrane
      proteins, in which folding and membrane insertion are coupled processes which
      involve at least four kinetically distinguishable steps.

PMID- 8855934
TI  - Nanosecond step-scan FTIR spectroscopy of hemoglobin: ligand recombination and
      protein conformational changes.
AB  - Step-scan FTIR spectroscopy with nanosecond time resolution is applied to the
      photocycle of carbonmonoxy hemoglobin (HbCO). The strong CO stretching band at
      1951 cm-1 serves as a convenient monitor of the state of ligation. Both geminate
      and second-order phases of CO recombination occur at rates which are in excellent
      agreement with previous visible absorption measurements, showing the molecular
      mechanisms to be unperturbed by the high protein concentrations (6.7 mM in heme)
      required for adequate protein signals. While the extent of photolysis (43%) was
      insufficient to drive the R-->T quaternary transition, the protein TRIR (time
      resolved infrared) difference bands (1250-1700 cm-1) nevertheless reveal
      interesting tertiary dynamics. Most of the bands are fully developed at very
      early times, possibly preceding the geminate recombination phase (tau = 50 ns).
      Some bands arise more slowly, however, with a time constant of 0.4 microsecond,
      reflecting a tertiary motion which is coincident with a quaternary motion
      previously detected by ultraviolet resonance Raman spectroscopy of fully
      photolyzed HbCO. Relaxation of the TRIR bands is either faster (tau =
      approximately 90 microseconds) or slower (tau = approximately 250 microseconds)
      than CO rebinding (effective time constant of 160 microseconds), suggesting
      either a distribution of tertiary processes or a chain inequivalence in CO
      rebinding.

PMID- 8855935
TI  - A protein kinase in the core of photosystem II.
AB  - In green plants, several intrinsic protein components of the photosystem II (PS
      II) complexes are subject to reversible phosphorylation on threonine residues.
      Evidence from mutant and inhibitor studies indicates that multiple kinases are
      involved. The protein kinases appear to be membrane-bound and redox-regulated,
      with activity requiring reducing conditions. We report the identification of a
      protein kinase activity which copurifies with a core complex of PS II and is
      capable of phosphorylating the photosystem proteins and associated light
      harvesting complex. The enzyme is a distinct and novel protein whose close
      proximity to the photosystem reaction center is confirmed by its rapid
      inactivation under strong red light irradiation in the presence of oxygen.

PMID- 8855936
TI  - Selective inhibition of free apolipoprotein-mediated cellular lipid efflux by
      probucol.
AB  - We attempted to demonstrate selective modulation of lipid-free apolipoprotein
      mediated cellular lipid efflux in order to test the hypothesis that it is an
      event independent of nonspecific physicochemical cholesterol exchange. Probucol,
      a unique cholesterol-lowering drug, was found to selectively suppress this
      pathway in vitro in mouse peritoneal macrophage. Probucol was given to the cells
      via the uptake of acetylated low-density lipoprotein (LDL) into which it had been
      incorporated. The uptake of lipoprotein-cholesteryl ester by the macrophage was
      the same whether the acetylated LDL was probucol-carrying or probucol-free, and
      probucol accumulated in the cell in parallel to cholesterol when carried by the
      lipoprotein. Incorporation of [35S]methionine into cell protein was unaffected by
      probucol accumulated in the cells. The efflux of cellular cholesterol and
      phospholipid mediated by lipid-free human apolipoproteins (apo) A-I, A-II, and E
      was all completely inhibited by probucol. Reversible binding of free apoA-I to
      the cellular surface was also completely blocked by probucol in this condition.
      On the other hand, nonspecific cholesterol exchange between LDL and macrophage
      was unaffected by probucol. Thus, probucol selectively inhibited apolipoprotein
      mediated cellular lipid efflux by blocking specific binding of free
      apolipoprotein to the cell without influencing nonspecific lipid exchange. In the
      absence of lecithin: cholesterol acyltransferase (LCAT) reaction, apparent
      cellular cholesterol efflux to high-density lipoprotein (HDL) was reduced by
      probucol by 40-70% while the rate of cholesterol influx from HDL to the cells was
      unaffected, resulting in cancellation of the net cellular cholesterol efflux to
      HDL. However, the increase of the net cholesterol efflux to HDL by LCAT was
      unaffected by probucol. Net cellular cholesterol efflux to HDL in the absence of
      LCAT, therefore, seems to depend on an apolipoprotein-mediated mechanism.

PMID- 8855937
TI  - Nonpolar interactions of thrombin and its inhibitors at the fibrinogen
      recognition exosite: thermodynamic analysis.
AB  - Nonpolar interactions play a major role in the association of the fibrinogen
      recognition exosite of thrombin with the C-terminal fragment (55-65), Asp-Phe-Glu
      IIe-Pro-Glu-Glu-Tyr-Leu-Gln, of hirudin, which is a naturally occurring thrombin
      inhibitor. The thermodynamic details (free energy, enthalpy, entropy, and heat
      capacity) of the molecular recognition are studied by using five analogs of a
      synthetic bivalent thrombin inhibitor (P552), tert-butylbenzensulfonyl-Arg-(D
      pipecolic acid)-(12-amino-dodecanoic acid)-(gamma-aminobutyric acid)-hirudin55
      65. The residue of PheH56, IleH59, ProH60, TyrH63, or LeuH64 in hirudin 55-65
      segment is substituted by Gly in each analog in order to elucidate the
      contributions of these nonpolar side chains. The results show that the
      interactions of these nonpolar side chains with thrombin are enthalpy-driven,
      except for the contribution of the PheH56 side chain which is entropy-driven.
      Interestingly, molecular modeling predicts a large conformational change due to
      the Gly substitution of PheH56. In analyzing the correlation among the
      thermodynamic and structural properties of the nonpolar interaction, a good
      correlation is observed between the binding free energy and the hydrophobicity of
      the molecular surface; i.e., tighter binding is observed as more nonpolar atoms
      are buried and more polar atoms are exposed upon molecular association.

PMID- 8855938
TI  - Bovine thrombin complexed with an uncleavable analog of residues 7-19 of
      fibrinogen A alpha: geometry of the catalytic triad and interactions of the P1',
      P2', and P3' substrate residues.
AB  - The crystal structure of the noncovalent complex of bovine thrombin and a
      fibrinogen-A alpha tridecapeptide substrate analog, G17 psi, in which the
      scissile bond amide nitrogen of Gly-17f has been replaced by a methylene carbon,
      has been determined at 2.3 A resolution with an R factor of 17.1%. The geometry
      of the active site indicates that the crystal structure is a close model of the
      true Michaelis complex. The three independently determined thrombin/G17 psi
      complexes in the crystal asymmetric unit reveal novel interactions for the P2'
      and P3' residues-Pro-18f and Arg-19f, respectively-on the carboxyl-terminal side
      of the scissile bond and confirm previously observed interactions of the P1 (Arg
      16f) through P10 (Asp-7f) positions on the amino-terminal side. The thrombin S2'
      binding site for Pro-18f, as observed in all three complexes, differs from that
      predicted by modeling studies and is notable for including two carbonyl oxygens
      of the thrombin main chain. Arg-19f occupies two binding sites on thrombin, S3'A
      and S3'B, which have dramatically different placements for the arginyl side chain
      and carboxyl terminus.

PMID- 8855939
TI  - Disulfide structure and N-glycosylation sites of an extracellular domain of
      granulocyte-colony stimulating factor receptor.
AB  - An extracellular domain containing 603 amino acid residues of human granulocyte
      colony stimulating factor receptor was expressed in Chinese hamster ovary cells.
      The affinity-purified material has previously been shown to dimerize when
      combined with the ligand. In this paper we have characterized the primary
      structure of this active receptor. Laser desorption mass spectrometry of the
      purified receptor showed a broad peak at a molecular weight of 84,000, ranging
      from 77,000 to 91,000. The molecular weight heterogeneity is due to
      glycosylation. Since the molecular weight based on the amino acid sequence is
      67,322, by subtraction the carbohydrate content is approximately 17,000.
      Disulfide structure of the receptor was determined by peptide mapping in the
      absence and presence of reducing agent. Sequence and mass spectral analyses of
      these peptides showed the receptor to contain eight disulfide bonds and three
      free cysteines. These disulfide bonds are consistent with the known domain motifs
      of the receptor in that no interdomain disulfides were present. One of the three
      free cysteines is reactive with alkylating agents, while the others are less
      reactive, probably being buried in the interior of the molecule. Blocking the
      free cysteines did not affect the ligand binding. Carbohydrate moieties are
      somewhat evenly spaced throughout the molecule, at eight different N
      glycosylation sites, some of which show heterogeneity in their compositions.
      Glycosylation seems necessary for stabilizing the molecule against disulfide
      linked oligomerization of the receptor, indicating that the free cysteine
      residues become reactive for oxidation and disulfide exchange upon
      deglycosylation.

PMID- 8855940
TI  - Interconverting receptor states at 4 degrees C for the neutrophil N-formyl
      peptide receptor.
AB  - With the aid of high time resolution kinetic data extracted from a flow
      cytometer, we determined that there are two N-formyl peptide receptor states for
      human neutrophils at 4 degrees C: a low affinity and a high affinity state.
      Competitive binding of FMLP, FNLP, and t-BOC with FNLPNTL-FL revealed different
      kinetic rate constants for two distinct reactions that control the lifetime of
      the low affinity ligand-receptor complex. For these ligands, the rate constant
      for dissociation of ligand from the low affinity receptor state (the first
      reaction) ranges in order of magnitude from 10(-2) to 1 s-1, and the conversion
      rate constant from the low affinity receptor state to the high affinity receptor
      state (the second reaction) ranges from 10(-4) to 10(-2) s-1. The antagonist t
      BOC differed most significantly from the three agonists by having an association
      rate constant for the low affinity receptor on the order of 10(5) M-1 s-1; the
      value for all three agonists was on the order of 10(7) M-1 s-1. Characterization
      of the receptor conversion at 4 degrees C revealed that it is irreversible (or
      very slow) and independent of Gi protein and that neither receptor state is a
      form of receptor precoupled to Gi protein. The affinity conversion and the
      dissociation characteristics of each receptor state determine the duration of the
      signaling complex and may contribute to differences in ligand efficacy.

PMID- 8855941
TI  - Degradation of cross-linked fibrin by matrix metalloproteinase 3 (stromelysin 1):
      hydrolysis of the gamma Gly 404-Ala 405 peptide bond.
AB  - Matrix metalloproteinases (MMPs) can degrade a number of proteins that constitute
      the extracellular matrix. Previous studies have shown that atherosclerotic
      plaques contain substantial amounts of fibrin(ogen)-related antigen, and more
      recently, MMPs have been identified in such lesions. The hypothesis that MMPs
      play a role in the degradation of fibrinogen (Fg) and cross-linked fibrin (XL-Fb)
      was investigated. Fibrinogen became thrombin-unclottable when treated with matrix
      metalloproteinase 3 (MMP-3, stromelysin 1) but not with matrix metalloproteinase
      2 (MMP-2, gelatinase A). Incubation of XL-Fb clots (made with 125I-Fg) with MMP-3
      resulted in complete lysis after 24 h. A D monomer-like fragment was generated by
      MMP-3 degradation of fibrinogen, XL-Fb, and fragment DD. Immunoreactivity with
      monoclonal antibody (MoAb)/4-2 (anti-gamma 392-406) but not with MoAb/4A5 (anti
      gamma 397-411) suggested that a major cleavage site was within the sequence
      participating in the cross-linking of two gamma-chains. NH2-terminal sequence
      analysis of they gamma-chain of the D monomer-like fragment and of a dipeptide
      isolated from the MMP-3 digest of XL-fibrin identified the hydrolysis of the
      gamma Gly 404-Ala 405 peptide bond. These data indicate that the degradation of
      Fg and XL-Fb by MMP-3 is specific and different from plasmin. This mechanism of
      fibrinolysis might be of relevance in wound healing, inflammation,
      atherosclerosis, and other pathophysiological processes.

PMID- 8855942
TI  - High-density lipoprotein 3 receptor-dependent endocytosis pathway in a human
      hepatoma cell line (HepG2).
AB  - The internalization of HLD3 into HepG2 cells at 37 degrees C was precisely
      measured, taking advantage of the previously observed rapid dissociation of HDL3
      from its two binding sites [Barbaras, R., et al. (1994) Biochemistry 33, 2335
      2340]. We observed a high level of HDL3 internalization (100 ng/mg of cell
      protein, corresponding to 45.5% of the total HDL3 associated to the cells at 37
      degrees C) reaching a plateau at 15 min. Apolipoprotein A-I (the main HDL3
      apolipoprotein) associated with dimyristoylphosphatidylcholine (DMPC) complexes
      was also internalized by HepG2 cells, at levels comparable to those obtained with
      HDL3 lipid-free apolipoprotein A-I, which can bind only to the HDL3 high-affinity
      binding site, and displayed a weak internalization (5 ng internalized/mg of cell
      protein compared to 250 ng/mg for apolipoprotein A-I complexed with DMPC).
      Clathrin-coated vesicle purification following HDL3 or LDL internalization at 37
      degrees C showed radioactivity associated with these vesicles, and further
      content analysis evidenced the presence of radiolabeled apoA-I and apoB,
      respectively. Treatment of the cells either by saccharose hypertonic shock or by
      potassium depletion, in order to block clathrin-coated vesicle formation,
      completely inhibited HDL3 internalization, as also observed with LDL. Altogether,
      these observations clearly demonstrate that HDL3 internalization into HepG2 cells
      occurs through an endocytosis pathway involving an interaction between
      apolipoprotein A-I and a cell surface protein, leading to the formation of
      clathrin-coated vesicles.

PMID- 8855943
TI  - Site-specific modification of interleukin-2 by the combined use of genetic
      engineering techniques and transglutaminase.
AB  - Exploring a new method for the site-specific incorporation of functional groups
      into proteins, we have studied the combined use of genetic engineering techniques
      and enzymatic methods. Specifically, a short peptide for use as a substrate of
      guinea pig liver transglutaminase (TGase) is introduced at the N terminus of
      human interleukin-2 (hIL-2). The expressed chimeric protein (rTG1-IL-2) is
      chemically modified at a glutamine site in the appended sequence by TGase
      catalyzed transamination with two amines, monodansylcadaverine (MDC), or a
      constructed derivative of poly (oxyethylene) (POE3). For the TGase-catalyzed
      modifications with MDC and POE3, 1 mol of donor was incorporated per mole of rTG1
      IL-2, respectively. N-Terminal sequence analysis of MDC-modified rTG1-IL-2 (MDC
      rTG1-IL-2) showed that the Gln-4 residue in the chimeric protein was site
      specifically modified with MDC. On the other hand, tryptic mapping of POE3
      modified rTG1-IL-2 (POE3-rTG1-IL-2) by matrix-assisted laser desorption/
      ionization time-of-flight mass spectrometry (MALDI-TOFMS) suggested that one of
      the Gln sites in the appended sequence was modified with POE3. The POE3-rTG1-IL-2
      retained full bioactivity relative to the unmodified molecule and rhIL-2. This
      methodology could be a new and general route for the site-specific modification
      of proteins.

PMID- 8855944
TI  - Characterization of monomeric forms of galectin-1 generated by site-directed
      mutagenesis.
AB  - Galectin-1 is a beta-galactoside-binding protein secreted by animal cells, and it
      exists in a monomer-dimer equilibrium (Kd approximately 7 microM). The
      function(s) of galectin-1 is(are) not yet defined, but dimerization and divalency
      are presumably important. Crystal structures of the mammalian galectin-1 dimer
      predict N- and C-terminal interactions at the subunit interface. To examine the
      mechanism of dimer formation and possibly generate active monomeric galectin-I,
      mutations were made in the N- and C-termini of recombinant hamster galectin-1. N
      Gal-1 contains disruptions of three hydrophobic amino acids at the N-terminus;
      V5D-Gal-1 contains a single mutation of Val5 to Asp; N/C-Gal-1 contains multiple
      changes in hydrophobic amino acids at both the N- and C-termini. All mutants
      behave as monomers in size-exclusion HPLC and native gel electrophoresis. N-Gal-1
      and V5D-Gal-1 bind weakly to lactosyl-Sepharose, but N/C-Gal-1 is nonfunctional.
      In equilibrium dialysis, N-Gal-1 and V5D-Gal-1 bind N-acetyllactosamine with a Kd
      approximately 90 microM, which is similar to that of native lectin. At high
      concentrations, V5D-Gal-1 and N-Gal-1 dimerize and can be covalently cross-linked
      with disuccinimidyl suberate. The Kd values of the monomer-dimer equilibrium for
      V5D-Gal-1 and N-Gal-1 are estimated to be approximately 60 microM and
      approximately 250 microM, respectively. The cross-linked dimers of V5D and N-Gal
      1 were isolated and were similar to native lectin in both hemagglutinating
      activity and high-affinity binding to lactosyl-Sepharose. Thus, specific
      mutations in galectin-1 can alter monomer-dimer equilibrium without affecting
      carbohydrate-binding activity. The availability of active monomers and functional
      covalent dimers of galectin-1 should aid in future studies aimed at understanding
      the biological function(s) of the lectin and the role of divalency.

PMID- 8855945
TI  - Site-directed mutagenesis of residues lining a putative proton transfer pathway
      in cytochrome c oxidase from Rhodobacter sphaeroides.
AB  - Several putative proton transfer pathways have been identified in the recent
      crystal structures of the cytochrome oxidases from Paracoccus denitrificans
      [Iwata et al. (1995) Nature 376, 660-669] and bovine [Tsukihara (1996) Science
      272, 1138-1144]. A series of residues along one face of the amphiphilic
      transmembrane helix IV lie in one of these proton transfer pathways. The possible
      role of these residues in proton transfer was examined by site-directed
      mutagenesis. The three conserved residues of helix IV that have been implicated
      in the putative proton transfer pathway (Ser-201, Asn-207, and Thr-211) were
      individually changed to alanine. The mutants were purified, analyzed for steady
      state turnover rate and proton pumping efficiency, and structurally probed with
      resonance Raman spectroscopy and FTIR difference spectroscopy. The mutation of
      Ser-201 to alanine decreased the enzyme turnover rate by half, and was therefore
      further characterized using EPR spectroscopy and rapid kinetic methods. The
      results demonstrate that none of these hydrophilic residues are essential for
      proton pumping or oxygen reduction activities, and suggest a model of redundant
      or flexible proton transfer pathways. Whereas previously reported mutants at the
      start of this putative channel (e.g., Asp-132-Asn) dramatically influence both
      enzyme turnover and coupling to proton pumping, the current work shows that this
      is not the case for all residues observed in this channel.

PMID- 8855946
TI  - Protein structural segments and their interconnections derived from optical
      spectra. Thermal unfolding of ribonuclease T1 as an example.
AB  - A novel descriptor for protein structure is examined here that goes beyond
      predictions of the average fractional components (FC) of a few conformational
      types and represents the number and interconnection of segments of continuous,
      well-defined secondary structural elements such as alpha-helices and beta-sheets.
      This matrix descriptor can be predicted from optical spectra using neural network
      methods. The new matrix plus traditional FC descriptors can be quickly and
      generally obtained to provide a level of detail not previously derived from
      optical spectra and a discrimination between proteins that might otherwise be
      viewed as being very similar using just the FC descriptor. As an example of its
      potential utilization, this matrix descriptor approach was applied to an analysis
      of both the native state and the reversible thermal denaturation of ribonuclease
      T1 in H2O. Analyses of the FTIR spectral data indicate initial loss of the major
      helical segment at 50-55 degrees C but with little accompanying change in the
      number of sheet segments or the sheet FC values. Circular dichroism (CD) and
      vibrational CD data are also used to support this interpretation based on FC
      changes with temperature. Parallel analysis of the corresponding data for this
      protein in D2O demonstrates that the method is sensitive to the match between the
      degree of H-D exchange used to prepare samples for the unknown and the reference
      data set.

PMID- 8855947
TI  - EPR detection and characterization of lignin peroxidase porphyrin pi-cation
      radical.
AB  - Lignin peroxidase (LiP) from Phanerochaete chrysosporium catalyzes the H2O2
      dependent one- and two-electron oxidations of substrates. The catalytic cycle
      involves the oxidation of ferric-LiP by H2O2 by two electrons to compound I,
      which is an oxoferryl heme and a free radical. It has been speculated that the
      unpaired electron is in a pi delocalized porphyrin radical. However, no direct
      evidence for the presence of the free radical has been reported. We present
      electron paramagnetic resonance (EPR) detection and characterization of compound
      I of LiP. The LiP compound I EPR signal is different than those reported
      previously for compound I of horseradish peroxidase and chloroperoxidase.
      However, the EPR signal of compound I of LiP (axial g tensor extending from
      gperpendicular = 3.42 to gparallel approximately 2) is very similar to the EPR
      signals of compound I of ascorbate peroxidase and catalase from Micrococcus
      lysodeikticus, in which the radical has been identified as a porphyrin pi-cation
      radical. On the basis of the analysis of our data and comparison with the earlier
      published results for compounds I of other peroxidases, we interpret the LiP
      compound I signal by a model for exchange coupling between an S = 1 oxyferryl [Fe
      = O]2+ moiety and a porphyrin pi-cation radical (S = 1/2) [Schulz, C.E., et al.
      (1979) FEBS Lett. 103, 102-105]. The exchange coupling is characterized by
      ferromagnetic rather than an antiferromagnetic interaction between the two
      species. The ferric-Lip EPR signal suggests that the iron in the heme is in near
      perfect orthogonal symmetry and provides additional evidence of the ferromagnetic
      interaction between the oxoferryl iron center and the porphyrin pi-cation
      radical.

PMID- 8855948
TI  - Role of hemopexin in protection of low-density lipoprotein against hemoglobin
      induced oxidation.
AB  - Globin-free hemin and certain hemoproteins, predominantly hemoglobin, are active
      triggers of low-density lipoprotein (LDL) peroxidation, a contributing cause of
      atherosclerosis. The role of the plasma heme-binding protein, hemopexin, in
      protecting apolipoprotein B and LDL lipids from oxidation triggered by either
      hemin or hemoglobin in the presence of low amounts of H2O2, was investigated at
      physiological pH and temperature. Significantly, hemopexin prevented not only
      hemin-mediated modification of LDL but also LDL peroxidation induced by
      hemoglobin, both by met and oxy forms. Analysis of the data revealed that the
      rate of heme transfer from methemoglobin to hemopexin was highly dependent upon
      temperature: only minimal heme transfer occurred at 20 degrees C, whereas at the
      physiological temperature of 37 degrees C, heme transfer was rapid, within the
      lag phase of LDL oxidation, regardless of the presence or absence of H2O2. Heme
      did transfer to hemopexin from oxyhemoglobin as well, but only in the presence of
      H2O2. The proposed mechanism of the inhibition of oxyhemoglobin oxidative
      reactivity by hemopexin involves peroxidation of oxyhemoglobin (Fe(II)) to
      ferrylhemoglobin (FeIV), followed by a comproportionation reaction (FeIV+FeII-
      >2FeIII), yielding methemoglobin (FeIII) from which heme is readily transferred
      to hemopexin. Taken together, the data demonstrate that hemopexin can act as an
      extracellular antioxidant against hemoglobin-mediated damage in inflammatory
      states, which is especially important when haptoglobin is depleted or absent.

PMID- 8855950
TI  - Structural polymorphism of homopurine DNA sequences. d(GGA)n and d(GGGA)n repeats
      form intramolecular hairpins stabilized by different base-pairing interactions.
AB  - DNA sequences containing homopurine d(G1-3A)n tracts are known to be capable of
      adopting non-B-DNA conformations. The structural polymorphism of these sequences
      is a direct consequence of the structural properties of the homopurine d(G1-3A)n
      tracts. Depending on the conditions, d(GA)n DNA sequences can form antiparallel
      and parallel-stranded homoduplexes, multistranded complexes, and ordered single
      stranded conformations. On the other hand, much less is known about the
      structural properties of d(GGA)n and d(GGGA)n sequences. In this paper, we show
      that d(GGA)n and d(GGGA)n repeats form antiparallel-stranded, intramolecular
      hairpins. Under physiological salt and pH conditions, the thermal stability of
      these hairpin forms is high, showing, at 50 mM NaCl, melting temperatures in the
      range of 40-50 degrees C. The base-pairing interactions involved in the formation
      of the d(GGA)n and d(GGGA)n hairpins are different. G.A pairs importantly
      contribute to the stability of the d(GGA)n hairpins. On the other hand, the
      d(GGGA)n hairpins are stabilized by the formation of G.G and A.A, but not G.A
      pairs. Homopurine d(G1-3A)n tracts are frequently found at genomic locations
      performing specialized chromosomal functions (i.e. telomeres, centromeres, and
      recombination "hot-spots"). The molecular interactions described here are
      relevant for the understanding of the peculiar structural and biological
      properties of DNA sequences containing homopurine tracts.

PMID- 8855949
TI  - Preparation and reactions of myoglobin mutants bearing both proximal cysteine
      ligand and hydrophobic distal cavity: protein models for the active site of P
      450.
AB  - We have reported that H93C human myoglobin (Mb), in which proximal histidine
      (His93, F8) was replaced by cysteine, gave nearly identical spectroscopic
      features of P-450 [Adachi, S., Nagano, S., Ishimori, K., Watanabe, Y., Morishima,
      I., Egawa, T., Kitagawa, T., & Makino R. (1993) Biochemistry 32, 241-252]. More
      importantly, the thiolate ligand enhanced its oxygenation activities when
      supported by H2O2 due to the exclusive encouragement of heterolytic O-O bond
      cleavage of peroxides. While we have attributed the enhanced heterolysis to the
      electron donation from the thiolate ligand, possible participation of the distal
      histidine (H64, E7) in H93C Mb cannot be eliminated. In addition, the racemic
      product formation catalyzed by H93C Mb implied that its distal cavity could
      prevent substrates from accessing to the heme and the reactions may proceed other
      than by the P-450 type mechanism (ferryl oxygen transfer). In order to clarify
      whether the distal histidine is involved in the O-O bond cleavage step and to
      improve accessibility of substrates, the distal histidine of H93C Mb is replaced
      by smaller and nonpolar residues, glycine (H64G/H93C Mb) and valine (H64V/H93C
      Mb), by site-directed mutagenesis. Various spectroscopic studies on these double
      mutated Mbs revealed the ligation of cysteine to the ferric heme as a thiolate
      form. In the reaction with cumene hydroperoxide, the anionic nature of the
      proximal cysteine in H64G/H93C and H64V/H93C Mbs was found to encourage the
      heterolytic O-O bond cleavage as observed for H93C Mb. The results clearly
      demonstrate that the distal histidine of H93C Mb is hardly involved in the O-O
      bond cleavage step and are in good agreement with the role of thiolate ligation
      for the formation of the reactive intermediate, equivalent to compound I, in the
      catalytic cycle of P-450 reactions. In the oxygenation of methyl p-tolyl sulfide,
      the ratios of ferryl oxygen transfer increased in H64G/H93C Mb (58%) and
      H64V/H93C Mb (78%) as compared to H93C Mb (53%). The increased ratios of ferryl
      oxygen transfer imply the active site of H64G/H93C and H64V/H93C Mbs being more
      accessible for substrates; however, the sulfoxidation by the ferric mutant
      Mbs/H2O2 system was much slower than that by H93C Mb. The poor activities of
      these mutant Mbs are attributed to the significantly discouraged binding of H2O2.

PMID- 8855951
TI  - DNA elements and protein factors involved in the transcription of the beta 2
      adrenergic receptor gene in rat liver. The negative regulatory role of C/EBP
      alpha.
AB  - Primer extension and RNase protection analyses of the rat beta 2-adrenergic
      receptor (beta 2AR) gene identify two transcription start points at -64 and -220
      nt, respectively. Transient transfections of putative promoter/pCAT constructs
      into DDT1 MF-2 cells indicate that fragments -36 to -100 (PI) and -186 to -312
      (P2) are sufficient to promote transcription, whereas -911 to -1122 contains a
      negative regulatory element(s). RNase protection analysis of the 3' untranslated
      region (3'-UTR) indicates the presence of two transcripts with 3'-UTR of 111 and
      604 nt exclusive of the poly(A+) tails. Northern blots of beta 2AR mRNA using
      full-length and partial cDNA probes indicate that a major 2.2 kb and a minor 1.6
      kb species arise from the use of alternative promoters as well as different
      polyadenylation signals. DNase I footprinting and DNA mobility shift assays
      (DMSA) using rat liver nuclear extracts identify a number of transcription
      factors binding to sequence elements within or upstream from P1 and P2, including
      Spl, CRE, CPl, AP-2, NF-1, NF-kappa B, and C/EBP. Supershift assays using
      antibodies against C/EBP alpha and C/EBP beta and mutational analyses indicate
      that the protein binding to the C/EBP consensus recognition site at -925 to -933
      is C/EBP alpha. The activity of promoter/CAT constructs containing the C/EBP
      recognition site is significantly decreased by cotransfection of C/EBP alpha but
      not C/EBP alpha but not C/EBP beta into either DDT1 MF-2 cells or primary rat
      hepatocytes. Partial hepatectomy causes a transient decrease in C/EBP alpha, as
      measured by DMSA, and an increase in beta 2 AR mRNA levels and rate of
      transcription in the remnant liver. Thus, derepression via C/EBP alpha is likely
      involved in the up-regulation of beta 2AR in the regenerating rat liver.

PMID- 8855952
TI  - Substrate specificity of Escherichia coli MutY protein.
AB  - The MutY protein of Escherichia coli removes mismatched deoxyadenine residues
      from DNA. In this study, duplex oligodeoxynucleotides containing modified bases
      are used as model substrates for this enzyme. In contrast to a recent report [Lu,
      A.-L., et al. (1995) J. Biol. Chem. 270, 23582], dA:8-oxo-dG appears to be the
      preferred natural substrate for MutY, as evidenced by the specificity constants
      (kcat/Km) for dA:8-oxo-dG and dA:dG of 39 600 x 10(-6) and 383 x 10(-6) (min-1 nM
      1), respectively. kcat for the duplex containing dA:dG was highest at lower pH;
      the rate of cleavage for the duplex containing dA:8-oxo-dG was unaffected over a
      pH range of 5.5-8.0. The presence of an 8-oxo function in dG increased
      significantly the rate of removal of dA from all substrates tested. Replacement
      of dA by rA reduced the specificity constant of dA:8-oxo-dG to 294 x 10(-6) (min
      1 nM-1), whereas replacement of dA by 2'-O-methyladenosine virtually abolished
      enzymatic activity. Modifications of the dG moiety generally were better
      tolerated than those of dA; however, introduction of a methyl ether at the 6
      position of dG produced a noncleavable substrate and replacement of dG by 2'-O
      methylguanosine generated a substrate with a low specificity constant. Rates of
      cleavage of duplexes containing dA:dC and dA:tetrahydrofuran were three orders of
      magnitude lower than the reference substrate. Duplexes containing a carbocyclic
      analog of dA were not cleaved. A model is proposed to explain the recognition of
      DNA substrates by MutY and the catalytic properties of this enzyme.

PMID- 8855953
TI  - ATP-binding site of human brain hexokinase as studied by molecular modeling and
      site-directed mutagenesis.
AB  - The interaction of ATP with the active site of hexokinase is unknown since the
      crystal structure of the hexokinase-ATP complex is unavailable. It was found that
      the ATP binding site of brain hexokinase is homologous to that of actin, heat
      shock protein hsc70, and glycerol kinase. On the basis of these similarities, the
      ATP molecule was positioned in the catalytic domain of human brain hexokinase,
      which was modeled from the X-ray structure of yeast hexokinase. Site-directed
      mutagenesis was performed to test the function of residues presumably involved in
      interaction with the tripolyphosphoryl moiety of ATP. Asp532, which is though to
      be involved in binding the Mg2+ ion of the MgATP2- complex, was mutated to Lys
      and Glu. The kcat values decreased 1000- and 200-fold, respectively, for the two
      mutants. Another residue, Thr680 was proposed to interact with the gamma
      phosphoryl group of ATP through hydrogen bonds and was mutated to Val and Ser.
      The kcat value of the Thr680Val mutant decreased 2000-fold, whereas the kcat
      value of the Thr680Ser decreased only 2.5-fold, implying the importance of the
      hydroxyl group. The Km and dissociation constant values for either ATP or glucose
      of all the above mutants showed little or no change relative to the wild-type
      enzyme. The Ki values for the glucose 6-phosphate analogue 1,5-anhydroglucitol 6
      phosphate, were the same as that of the wild-type enzyme, and the inhibition was
      reversed by inorganic phosphate (Pi) for all four mutants. The circular dichroism
      spectra of the mutants were the same as that of the wild-type enzyme. The results
      from the site-directed mutagenesis demonstrate that the presumed interactions of
      investigated residues with ATP are important for the stabilization of the
      transition state.

PMID- 8855954
TI  - Mechanistic consequences of mutation of active site carboxylates in a retaining
      beta-1,4-glycanase from Cellulomonas fimi.
AB  - The exoglucanase/xylanase Cex from Cellulomonas fimi is a retaining glycosidase
      which functions via a two-step mechanism involving the formation and hydrolysis
      of a covalent glycosyl-enzyme intermediate. The roles of three conserved active
      site carboxylic acids in this enzyme have been probed by detailed kinetic
      analysis of mutants modified at these three positions. Elimination of the
      catalytic nucleophile (E233A) results in an essentially inactive enzyme,
      consistent with the important role of this residue. However addition of small
      anions such as azide or formate restores activity, but as an inverting enzyme
      since the product formed under these conditions is the alpha-glycosyl azide.
      Shortening of the catalytic nucleophile (E233D) reduces the rates of both
      formation and hydrolysis of the glycosyl-enzyme intermediate some 3000-4000-fold.
      Elimination of the acid/base catalyst (E127A) yields a mutant for which the
      deglycosylation step is slowed some 200-300-fold as a consequence of removal of
      general base catalysis, but with little effect on the transition state structure
      at the anomeric center. Effects on the glycosylation step due to removal of the
      acid catalyst depend on the aglycon leaving group ability, with minimal effects
      on substrates requiring no general acid catalysis but large (> 10(5)-fold)
      effects on substrates with poor leaving groups. The Bronsted beta 1g value for
      hydrolysis of aryl cellobiosides was much larger (beta 1g approximately -1) for
      the mutant than for the wild-type enzyme (beta 1g = -0.3), consistent with
      removal of protonic assistance. The pH-dependence was also significantly
      perturbed. Mutation of a third conserved active site carboxylic acid (E123A)
      resulted in rate reductions of up to 1500-fold on poorer substrates, which could
      be largely restored by addition of azide, but without the formation of glycosyl
      azide products. These results suggest a simple strategy for the identification of
      the key active site nucleophile and acid/base catalyst residues in glycosidases
      without resort to active site labeling.

PMID- 8855955
TI  - Thermodynamic analysis of the effects of small inert cosolutes in the
      ultracentrifugation of noninteracting proteins.
AB  - Considerations of the effect of a small cosolute on the sedimentation equilibrium
      distribution for a noninteracting protein have led to the development of a simple
      procedure for evaluating both the molecular weight of the protein and the second
      virial coefficient describing the excluded volume interaction between protein and
      cosolute. Its application is illustrated by analysis of sedimentation equilibrium
      distributions for bovine thyroglobulin and horse liver alcohol dehydrogenase in
      the presence of a range of sucrose concentrations, and also of those for aldolase
      in the presence of urea to obtain the subunit molecular weight of this tetrameric
      enzyme. The effects of sucrose concentration on the sedimentation coefficients of
      thyroglobulin, catalase, and horse liver alcohol dehydrogenase are also examined
      to demonstrate that the second virial coefficients for protein-cosolute excluded
      volume interaction may be determined, albeit with less precision, from the
      cosolute concentration required to render the sedimentation coefficient zero by
      virtue of its effect on the buoyancy term. These findings serve to reinforce the
      fact that the effects of small cosolutes usually ascribed to changes in "protein
      solvation" are envisaged more realistically in terms of excluded volume.

PMID- 8855956
TI  - Different sensitivities to acid denaturation within a family of proteins:
      implications for acid unfolding and membrane translocation.
AB  - Colicins A, B, and N form a family of membrane pore-forming toxins with > 50%
      sequence identity in their toxic C-terminal domains. The colicin A C-terminal
      domain has been shown to insert into model membranes via an acidic molten-globule
      insertion intermediate, and thus this family provides a means to compare acid
      unfolding of related proteins. Unlike the domains of colicins A and B which are
      acidic, that of colicin N is very basic with fewer Asp and Glu residues. If
      surface positive charge density is the crucial factor in acidic molten globule
      formation, colicin N should begin to unfold at higher pH values than colicins A
      or B. However, comparison of their CD spectra reveals that colicins A and B both
      form acidic molten globules but colicin N does not. None of the proteins forms a
      denaturant-induced molten globule at neutral pH where the proteins exhibit very
      similar stabilities. The acidic unfolding cannot therefore be due to excess
      positive surface charge and may be caused by a subset of acidic residues as has
      been predicted for myoglobin. The difference between the colicins is confirmed by
      their in vivo membrane insertion, with colicins A and B inserting much faster
      than colicin N. Stopped-flow circular dichroism measurements of colicin A
      insertion into vesicles confirmed that a molten globule insertion intermediate
      occurs at the membrane surface.

PMID- 8855957
TI  - Kinetic characterization and X-ray structure of a mutant of haloalkane
      dehalogenase with higher catalytic activity and modified substrate range.
AB  - Conversion of halogenated aliphatics by haloalkane dehalogenase proceeds via the
      formation of a covalent alkyl-enzyme intermediate which is subsequently
      hydrolyzed by water. In the wild type enzyme, the slowest step for both 1,2
      dichloroethane and 1,2-dibromoethane conversion is a unimolecular enzyme
      isomerization preceding rapid halide dissociation. Phenylalanine 172 is located
      in a helix-loop-helix structure that covers the active site cavity of the enzyme,
      interacts with the C1 beta of 1,2-dichloroethane during catalysis, and could be
      involved in stabilization of this helix-loop-helix region of the cap domain of
      the enzyme. To obtain more information about the role of this residue in
      dehalogenase function, we performed a mutational analysis of position 172 and
      studied the kinetics and X-ray structure of the Phe172Trp enzyme. The Phe172Trp
      mutant had a 10-fold higher Kcat/Km for 1-chlorohexane and a 2-fold higher Kcat
      for 1,2-dibromoethane than the wild-type enzyme. The X-ray structure of the
      Phe172Trp enzyme showed a local conformational change in the helix-loop-helix
      region that covers the active site. This could explain the elevated activity for
      1-chlorohexane of the Phe172Trp enzyme, since it allows this large substrate to
      bind more easily in the active site cavity. Pre-steady-state kinetic analysis
      showed that the increase in Kcat found for 1,2-dibromoethane conversion could be
      attributed to an increase in the rate of an enzyme isomerization step that
      preceeds halide release. The observed conformational difference between the helix
      loop-helix structures of the wild-type enzyme and the faster mutant suggests that
      the isomerization required for halide release could be a conformational change
      that takes place in this region of the cap domain of the dehalogenase. It is
      proposed that Phe172 is involved in stabilization of the helix-loop-helix
      structure that covers the active site of the enzyme and creates a rigid
      hydrophobic cavity for small apolar halogenated alkanes.

PMID- 8855958
TI  - Design and synthesis of amphiphilic alpha-helical model peptides with
      systematically varied hydrophobic-hydrophilic balance and their interaction with
      lipid- and bio-membranes.
AB  - Five amphiphilic alpha-helical peptides of 18 residues containing a hydrophobic
      Trp residue as a fluorescence probe were designed. The peptides were made up of
      hydrophobic Leu and hydrophilic Lys residues of a ratio of 13:5, 11:7, 9:9, 7:11,
      and 5:13 (abbreviated as Hels 13-5, 11-7, 9-9, 7-11, and 5-13, respectively).
      These peptides generate ideal amphiphilic alpha-helical structures, which have
      systematically varied hydrophobic-hydrophilic balance (relative amphiphilic
      potential) as a result of different hydrophobicities and almost the same
      hydrophobic moments. Their hydrophobic-hydrophilic balance was estimated both
      theoretically from the calculated hydrophobicity values (or the magnitude of
      hydrophobic faces) and experimentally from the retention times in reverse phase
      high-performance liquid chromatography (RP-HPLC). Circular dichroism, liposome
      lytic, and Trp-fluorescent studies in buffer and in the presence of acidic and
      neutral liposomes clearly showed that the increasing hydrophobic face area not
      only increases the affinity for lipid but also increases the trend of self
      association. The structure-activity relationship estimated by means of leakage
      ability and hemolytic activity demonstrated that the model- and bio-membrane
      perturbation ability is completely parallel to the magnitude of the hydrophobic
      face area. The lipid-binding study in guanidine hydrochloride solution showed
      that the peptides with a hydrophobic face larger than the hydrophilic face (Hels
      13-5 and 11-7) immerse their hydrophobic regions in lipid bilayers and that the
      inverse ones (Hels 7-11 and 5-13) interact only between the anionic lipid head
      groups and cationic peptide residues on liposome surfaces. The peptide Hel 9-9,
      which has exactly the same hydrophobic and hydrophilic regions, was found to be
      at a critical boundary among these peptides in terms of (1) behavior of peptide
      self-aggregation in buffer solution and membrane perturbation ability, (2)
      transfer from bulk solution to neutral lipid bilayers, and (3) necessity of
      charge interaction in lipid-peptide binding.

PMID- 8855959
TI  - Dimerization of a His117Gly azurin mutant by external addition of 1,omega
      di(imidazol-1-yl)alkanes.
AB  - The possibility to construct non-covalently linked protein dimers was
      investigated by employing the His117Gly mutant of the Cu containing azurin and
      the bifunctional 1,omega-di(imidazol-1-yl)alkanes as linkers. The His117Gly
      mutation creates a gap in the coordination sphere of the metal through which the
      latter becomes accessible for externally added ligands. The bifunctional ligands
      gave rise to the formation of dimers provided the linker was sufficiently long,
      as in the case of 1,omega-di(imidazol-1-yl)pentane and -hexane; the butane linker
      only produced monomers. The binding of the azurin molecules to the bifunctional
      C5 and C6 linkers showed cooperativity, which is the result of the hydrophobic
      interaction of the aligned hydrophobic patches. The energy and surface area
      involved in this process have been estimated from the experimental data to be
      delta G is -1.3 to -2.1 kcal/mol and 65-105 A2. The implications for the study of
      electron transfer processes inside a protein matrix are indicated.

PMID- 8855960
TI  - Isolation and characterization of neutralizing single-chain antibodies against
      Xenopus mitogen-activated protein kinase kinase from phage display libraries.
AB  - MAP kinase kinase (MAPKK) is a dual specificity protein kinase that
      phosphorylates and activates MAP kinase in vivo. In this study, four mouse
      monoclonal single-chain Fv (scFv) antibodies (Y1-6, Y1-7, Y3-6, and Y3-11) that
      can specifically bind to Xenopus MAPKK were isolated from combinatorial scFv
      displaying phage libraries. Three scFv clones (Y1-6, Y1-7, and Y3-6) were shown
      to efficiently inhibit MAPKK activity in vitro. Point mutation (D98K) at VH-CDR3
      of one (Y1-6) of these three clones markedly reduced its neutralizing activity.
      The wild-type scFv (Y1-6) inhibited the Mos-induced MAP kinase activation and
      germinal vesicle breakdown when injected into immature Xenopus oocytes, whereas
      the mutant scFv, Y1-6 (D98K), did not. The three neutralizing scFv clones (Y1-6,
      Y1-7, and Y3-6) were shown to bind to NH2-terminal residues 1-23 of Xenopus
      MAPKK, whereas the epitope of a Y3-11 clone with no neutralizing activity was
      shown to lie between residues 33 and 67 of MAPKK. Furthermore, a synthetic
      peptide (the N16 peptide) corresponding to residues 2-17 of MAPKK suppressed the
      neutralizing activity of the wild-type Y1-6, and a rabbit polyclonal antibody
      against the N16 peptide was found to possess a strong neutralizing activity
      against MAPKK. These results demonstrate that the neutralizing antibodies
      characterized here inhibit the kinase activity of MAPKK by binding to the NH2
      terminal segment of MAPKK.

PMID- 8855961
TI  - Activation of a Ca(2+)-dependent protein kinase involves intramolecular binding
      of a calmodulin-like regulatory domain.
AB  - Ca(2+)-dependent protein kinases (CDPKs) are regulated by a C-terminal calmodulin
      like domain (CaM-LD). The CaM-LD is connected to the kinase by a short junction
      sequence which contains a pseudosubstrate autoinhibitor. To understand how the
      CaM-LD regulates a CDPK, a recombinant CDPK (isoform CPK-1 from Arabidopsis,
      accession no. L14771) was made as a fusion protein in Escherichia coli. We show
      here that a truncated CDPK lacking a CaM-LD (e.g. mutant delta NC-26H) can be
      activated by exogenous calmodulin or an isolated CaM-LD (Kact approximately 2
      microM). We propose that Ca2+ activation of a CDPK normally occurs through
      intramolecular binding of the CaM-LD to the junction. When the junction and CaM
      LD are made as two separate polypeptides, the CaM-LD can bind the junction in a
      Ca(2+)-dependent fashion with a dissociation constant (KD) of 6 x 10(-6) M, as
      determined by kinetic binding analyses. When the junction and CaM-LD are tethered
      in a single polypeptide (e.g. in protein JC-1), their ability to engage in
      bimolecular binding is suppressed (e.g. the tethered CaM-LD cannot bind a
      separate junction). A mutation which disrupts the putative CaM-LD binding
      sequence (e.g. substitution LRV-1444 to DLPG) appears to block intramolecular
      binding, as indicated by the restored ability of a tethered CaM-LD to engage in
      bimolecular binding. This mutation, in the context of a full-length enzyme
      (mutant KJM46H), appears to block Ca2+ activation. Thus, a disruption of
      intramolecular binding correlates with a disruption of the Ca2+ activation
      mechanism. CDPKs provide the first example of a member of the calmodulin
      superfamily where a target binding sequence is located within the same
      polypeptide.

PMID- 8855962
TI  - Regulation of GLUT1-mediated sugar transport by an antiport/uniport switch
      mechanism.
AB  - Avian erythrocyte sugar transport is stimulated during anoxia and during exposure
      to inhibitors of oxidative phosphorylation. This stimulation results from
      catalytic desuppression of the cell surface glucose transporter GLUT1 [Diamond,
      D., & Carruthers, A. (1993) J. Biol. Chem. 268, 6437-6444]. The present study was
      undertaken to investigate the mechanisms of GLUT1 suppression/desuppression.
      Sugar uniport (sugar uptake or exit in the absence of sugar at the opposite side
      of the membrane) is absent in normoxic avian erythrocytes, but sugar antiport
      (sugar uptake coupled to sugar exit) is present. Exposure to cyanide and/or to
      FCCP (mitochondrial inhibitors) stimulates erythrocyte sugar uniport but not
      sugar antiport. K(m)(app) for 3-O-methylglucose uniport and antiport are
      unaffected by metabolic poisoning. Ki(app) for inhibitions of 3-O-methylglucose
      uniport by cytochalasin B and forskolin (sugar export site ligands) are
      unaffected by progressive stimulation of sugar uniport. Cyanide and FCCP
      stimulation of 3-O-methylglucose uniport are associated with increased AMP
      activated protein kinase activity. Purified human GLUT1 is not phosphorylated by
      exposure to cytosol extracted from poisoned avian erythrocytes. FCCP does not
      stimulate GLUT1-mediated 3-O-methylglucose uptake in K562 cells but does increase
      K562 AMP-activated protein kinase activity. FCCP stimulation of 3-O-methylglucose
      uniport in resealed erythrocyte ghosts requires cytosolic ATP and/or glutathione.
      The nonmetabolizable ATP analog AMP-PNP cannot be substituted for ATP in this
      action. These results are contrasted with allosteric regulation of human
      erythrocyte sugar transport and suggest that avian erythrocyte sugar transport
      suppression results from inhibition of carrier uniport function. Uniport
      suppression is not mediated by interaction with cytosolic molecular species that
      bind to the sugar export site. The antiport to uniport switch mechanism requires
      ATP hydrolysis, is associated with elevated AMP-activated kinase function, and,
      if triggered by this kinase, is mediated by factors absent in K562 cells and
      downstream from the kinase.

PMID- 8855963
TI  - Physical and biological characteristics of the antitumor drug actinomycin D
      analogues derivatized at N-methyl-L-valine residues.
AB  - The crystal structure of the DNA-actinomycin D (AMD) complex and a simple
      molecular modeling study indicated that AMD analogues derivatized at N-methyl-L
      valine residues (fifth amino acid residue in the cyclic depsipeptide of AMD)
      could bind to DNA as strongly as the parent AMD. The analogues in which N-methyl
      L-valine residues were replaced with L- and D-forms of N-methylvalines, N
      methylthreonines, N-methylphenylalanies, N-methyltyrosines, and N-methyl-O
      methyltyrosines have been totally synthesized. The characteristics of binding of
      the analogues to various DNAs including DNA-1 [d(TATATATGCATATATA)], DNA-2
      [d(TATATACGCGTATATA)], DNA-3 [d(ATATATAGCTATATAT)], and DNA-4
      [d(ATATATGGCCATATAT)] have been examined by using visible absorption spectrum
      methods. The association constants calculated from the absorption spectra
      indicate that the modifications of the N-methyl-L-valine residues in the AMD
      molecule do affect the DNA binding characteristics of the analogues. The L
      aromatic analogues bind slightly better than the L-aliphatic analogues except for
      binding to DNA-1 (-TGCA-), whereas the D-aliphatic analogues bind consistently
      better than the D-aromatic analogues. In the L-form analogues, the L-Tyr analogue
      has the highest overall association constant, whereas the D-Val analogue has the
      highest association constant among the D-form analogues. In spite of substitution
      of bulky aromatic groups, the D-aromatic analogues bind to the DNA-1 quite well.
      However, D-aromatic analogues have significantly reduced their binding capacities
      to the other DNAs, indicating that the substitution of the D-aromatic residues
      creates a unique four-base sequence preference (-TGCA-). The RNA polymerase
      inhibitory activities of the AMD analogues in vivo have been examined using human
      cells (HeLa). All AMD analogues except for the L-Thr analogues severely inhibit
      RNA synthesis at relatively low drug concentrations. The D-Val, L-OMT, L-Phe, and
      D-Phe analogues inhibit RNA synthesis more strongly than the natural antibiotic
      (AMD itself).

PMID- 8855964
TI  - RNA folding topology and intermolecular contacts in the AMP-RNA aptamer complex.
AB  - We report below on the NMR structural characterization of the complex between AMP
      and a 40-mer RNA aptamer in aqueous solution. Resonance assignments are based on
      multinuclear multidimensional NMR studies on complexes uniformly 13C, 15N-labeled
      with either AMP or the RNA aptamer. AMP binds to an internal loop (labeled G7-G8
      A9-A10-G11-A12-A13-A14-C15-U16-G17) and bulge (G34 positioned opposite the
      internal loop) segment in the RNA aptamer, and our NMR study provides insights
      into features of the RNA folding topology and the molecular recognition events in
      the AMP binding pocket on the RNA. Specifically, the helical stems are extended
      by G-G mismatch formation from either direction into the internal loop/bulge
      segment of the RNA aptamer on complex formation. The internal loop adopts a
      unique fold with the purine ring of AMP intercalated between A10 and G11 in the
      complex. The G8-A9-A10-AMP segment adopts certain stacking features in common
      with a GNRA turn and is closed by the G7.G11 mismatch pair. The purine rings of
      A12 and G34 (syn) are stacked on each other and participate in stablizing the AMP
      intercalation site. A large number of intermolecular NOEs have been identified
      between the AMP ligand and the G8, A10, G11, G17, U18, and G34 residues on the
      RNA aptamer in the complex. The Watson-Crick edge of the AMP is oriented toward
      the exocyclic amino group of G8, suggestive of a hydrogen-bonding alignment
      between G8 and AMP in the complex. The AMP sugar ring is positioned in the minor
      groove of the rightward helical stem centered about the G17.G34 mismatch and
      U18.A33 Watson-Crick pairs. The AMP binds to one face of the folded internal
      loop/bulge segment of the RNA aptamer while the opposite face is capped by a
      stacked alignment of the A13-A14-C15-U16 segment located toward the 3'-end of the
      internal loop segment. Globally, the two helical stems of the RNA aptamer are
      aligned approximately orthogonal to each other with tertiary interactions
      centered about the internal loop/bulge segment generating the AMP binding site on
      the RNA.

PMID- 8855965
TI  - Expression of the extracellular matrix protein tenascin in malignant and benign
      ovarian tumours.
AB  - The extracellular matrix protein tenascin (TN) is overexpressed in a number of
      solid tumours. Thi however, is the first study to examine TN expression in
      ovarian tumours. TN protein was examined in froze sections of 50 human ovarian
      tumours by immunohistochemistry. Malignant and borderline tumours showed
      significantly greater incidence and intensity of stromal staining than benign
      tumours (P < 0.0001 and P = 0.038 respectively). Seven omental metastases were
      also examined and showed a strikingly similar protein distribution to their
      primary tumour counterparts. The expression pattern of different RNA isoforms,
      created by alternative splicing of the primary transcript, was identified using
      reverse transcription-polymerase chain reactions (RT-PCR). The smallest TN RNA
      splice variant (284 bp) was found in all tumours examined, while the appearance
      of larger molecular weight transcripts (approximately 490 and 556 bp), as major
      forms, was predominantly limited to malignant tumours, with 9/12 malignant
      tumours showing this pattern compared with 1/6 benign tumours. These data suggest
      that malignant ovarian tumours have increased expression of TN compared with
      benign tumours and this may be associated with induction of specific isoforms.

PMID- 8855966
TI  - Differential expression of gp200-MR6 molecule in benign hyperplasia and down
      regulation in invasive carcinoma of the breast.
AB  - In this study, we used immunohistochemical and biochemical analysis to show that
      gp200-MR6, a 200 kDa molecule that is functionally associated with the human
      interleukin 4 (IL-4) receptor complex, is expressed at high levels on normal
      breast epithelial tissues, at lower levels on in situ carcinomas, and that the
      expression is lost in the invasive carcinoma of the breast. Furthermore, a
      preliminary study showed that benign epithelial hyperplasia of the breast
      expresses the gp200-MR6 heterogeneously. Two populations of cells have been
      observed: MR6 positive and MR6 negative. Interestingly, MR6-positive cells were
      observed to have different morphology from those that were MR6 negative; the
      nuclei of the former were larger and rounded in shape, whereas the nuclei of the
      latter were relatively small and oval in shape. In sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, monoclonal
      antibody MR6 detects the same molecular weight molecule in both normal and
      transformed tissue, indicating that the molecule is not a product of a truncated
      gene. The intensity of the gp200-MR6 bands correlates with the
      immunohistochemical data, indicating that the molecule is expressed at high
      levels in normal tissue and at lower levels in malignant tissue. These results
      suggest that analysis of gp200-MR6 expression may be useful in tumour grading and
      prognostic evaluation in breast cancer. Moreover, the molecule may be involved
      early in the process of tumorigenesis of the breast, in which a loss or a down
      regulation of gp200-MR6 could contribute towards tumour development and
      progression via an effect on cell growth and differentiation.

PMID- 8855967
TI  - The prognostic significance of tumour cell proliferation in squamous cell
      carcinomas of the oesophagus.
AB  - Tumour samples from 150 patients with squamous cell carcinoma of the oesophagus
      were investigated immunohistochemically with the monoclonal antibody MIB-1, which
      recognises proliferating cells. Using light microscopy, the number of MIB-1
      positive tumour cells was counted in the areas with the highest proliferative
      activity. The MIB-1 index was determined as the proportion of MIB-1-positive and
      MIB-1-negative tumour cells. A considerable variation of the MIB-1 indices was
      found between the different tumours with a minimum of 6% and a maximum of 95%
      (median, 33%). The MIB-1 index correlated significantly with the mitotic activity
      in the tumour tissue (r = 0.33; P = 0.0001) and with the proportion of apoptotic
      tumour cells (r = 0.25; P = 0.0017). No significant correlation was found between
      the MIB-1 index and various other prognostic parameters including pT
      classification, pN classification, tumour grade, blood vessel invasion and
      lymphatic vessel invasion. In the univariate survival analysis no significant
      difference was found between tumours with low (< or = 33%) and high MIB-1 index
      (> 33%) 5-year survival rate: low MIB-1 index, 19.2%; high MIB-1 index, 22.2%).
      In a Cox proportional hazard regression analysis only the parameters lymphatic
      vessel invasion (P = 0.0001), pT classification (P = 0.0034) and pN
      classification (P = 0.0256), but not the MIB-1 index, could be verified as
      independent prognostic variables. In conclusion, evaluation of the MIB-1 index
      does not provide prognostic information for oesophageal cancer patients.

PMID- 8855968
TI  - BB-10010/MIP-1 alpha in vivo maintains haemopoietic recovery following repeated
      cycles of sublethal irradiation.
AB  - Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is an inhibitor of stem
      cell proliferation affording protection against damage from agents that express
      their cytotoxicity specifically in the DNA synthesis phase of the cell cycle. Its
      ability also to modify the self-renewal capacity of the regenerating cells is now
      shown to improve and maintain haemopoietic recovery following therapy (sublethal
      irradiation) whose cytotoxic damage is not limited solely to the DNA-S phase of
      this cycle. Such non-cell cycle-active cytotoxic agents are used clinically in
      repeated treatment regimens, which are often limited or terminated because of
      accumulating haemopoietic damage. BB-10010, a non-aggregating variant of MIP-1
      alpha, was administered as a continuous dose (1600 micrograms kg-1 24 h-1) via a
      subcutaneously implanted pump over a period of 7 days. A dose of 4.5 Gy total
      body gamma-rays was given 3-4 h after implantation. Day 8 and 12 spleen colony
      forming units (CFU-S) were assayed on days 1, 7 and 14 after irradiation. This
      cycle of treatment was repeated four times (total 56 days), and on day 14 of the
      last two cycles the marrow-repopulating ability (MRA) was also measured. In the
      control bone marrow (no BB-10010) CFU-S fell to < 1% of normal within 1 day of
      irradiation and recovered to 40% at 14 days. Repeated treatments increased the
      level of damage, and after four cycles CFU-S recovered to only 10% of normal. BB
      10010 afforded little benefit in the first treatment cycle, but by the end of the
      fourth cycle CFU-S still recovered to 35% of normal. MRA was reduced to 7% of
      normal by the irradiation protocol-about half that maintained by BB-10010
      protection. We conclude that BB-10010 (MIP-1 alpha) reduces the degree of
      accumulated haemopoietic stem cell damage following repeated non-cell cycle
      specific cytotoxic insults-a principle which should be valuable in repeated
      clinical cytotoxic therapy regimens.

PMID- 8855969
TI  - Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in
      vitro and in vivo.
AB  - This paper deals with the utility of immunoliposomes for the delivery of
      doxorubicin (DXR) to human ovarian carcinoma cells in vitro and in vivo. We aimed
      to investigate whether immunoliposome-mediated targeting of DXR to ovarian cancer
      cells translates in an enhanced anti-tumour effect compared with that of non
      targeted DXR liposomes (lacking the specific antibody). Target cell binding and
      anti-tumour activity of DXR immunoliposomes were studied in vitro and in vivo
      (xenograft model of ovarian carcinoma). In vitro we observed that target cell
      binding and cell growth inhibition of DXR immunoliposomes is superior to that of
      non-targeted DXR-liposomes. However, in vivo, despite the efficient target cell
      binding and good anti-tumour response of DXR-immunoliposomes, no difference in
      anti-tumour effect, compared with non-targeted DXR-liposomes, could be
      determined. The results indicate that premature DXR leakage from immunoliposomes
      occurring before the actual target cell binding and subsequent DXR association
      with the tumour cells, explains why no significant differences in anti-tumour
      activity between DXR-immunoliposomes and non-targeted DXR-liposomes were observed
      in vivo.

PMID- 8855970
TI  - 3-aminobenzamide and/or O6-benzylguanine evaluated as an adjuvant to temozolomide
      or BCNU treatment in cell lines of variable mismatch repair status and O6
      alkylguanine-DNA alkyltransferase activity.
AB  - O6-benzylguanine (O6-BG) and 3-aminobenzamide (3-AB) inhibit the DNA repair
      proteins O6-alkylguanine-DNA alkyltransferase (AGT) and poly(ADP-ribose)
      polymerase (PARP) respectively. The effect of O6-BG and/or 3-AB on temozolomide
      and 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) cytotoxicity, was assessed in seven
      human tumour cell lines: six with an AGT activity of > 80 fmol mg-1 protein
      (Mer+) and one with an AGT activity of < 3 fmol mg-1 protein (Mer-). Three of the
      Mer+ cell lines (LS174T, DLD1 and HCT116) were considered to exhibit resistance
      to methylation by a mismatch repair deficiency (MMR-), each being known to
      exhibit microsatellite instability, and DLD1 and HCT116 having well-characterised
      defects in DNA mismatch binding. Potentiation was defined as the ratio between an
      IC50 achieved without and with a particular inhibitor treatment. Temozolomide or
      BCNU cytotoxicity was not potentiated by either inhibitor in the Mer- cell line.
      Preincubation with O6-BG (100 microM for 1 h) was found to potentiate the
      cytotoxicity of temozolomide by 1.35- to 1.57-old in Mer+/MMR+ cells, but had no
      significant effect in Mer+/MMR- cells. In comparison, O6-BG pretreatment enhanced
      BCNU cytotoxicity by 1.94- to 2.57-fold in all Mer+ cell lines. Post-incubation
      with 3-AB (2 mM, 48 h) potentiated temozolomide by 1.35- to 1.59-fold in
      Mer+/MMR+ cells, and when combined with O6-BG pretreatment produced an effect
      which was at least additive, enhancing cytotoxicity by 1.97- to 2.16-fold. 3-AB
      treatment also produced marked potentiation (2.20- to 3.12-fold) of temozolomide
      cytotoxicity in Mer+/MMR- cells. In contrast, 3-AB produced marginal potentiation
      of BCNU cytotoxicity in only three cell lines (1.19- to 1.35-fold), and did not
      enhance the cytotoxicity of BCNU with O6-BG treatment in any cell line. These
      data suggest that the combination of an AGT and PARP inhibitor may have a
      therapeutic role in potentiating temozolomide activity, but that the inhibition
      of poly(ADP-ribosyl)ation has little effect on the cytotoxicity of BCNU.

PMID- 8855971
TI  - Apoptotic and non-apoptotic cell death induced by cis and trans analogues of a
      novel ammine(cyclohexylamine)dihydroxodichloroplatinum(IV) complex.
AB  - It has been previously demonstrated that cisplatin induces apoptosis in the CH1
      human ovarian carcinoma cell line. This study demonstrates that two novel
      platinum (Pt) analogues JM149 and JM335, which are the cis and trans geometry
      respectively of ammine(cyclohexylamine)dihydroxodichloroPt(IV), initiate
      apoptosis in this cell line at physiologically relevant concentrations (IC50
      values 2 h drug exposure were 35.3 microM for JM149 and 18.7 microM for JM335).
      While at equimolar drug concentrations there was a 2-fold higher level of total
      platinum-DNA adducts following exposure to JM335 vs JM149, at equitoxic
      concentrations, levels were similar (80 vs 70 pmol Pt mg-1 DNA respectively).
      Following a 2 h incubation with 2 x IC50 of both drugs, cells rounded up and
      detached in a time-dependent manner but with the kinetics of apoptosis being more
      rapid for JM335. The majority of detached cells exhibited morphology associated
      with apoptosis which was further supported by the presence of a 50 kb fragment
      detected in DNA lysates prepared from these cells. JM149 induced apoptosis across
      a range of concentrations (2 x, 5 x and 10 x IC50) with a 50 kb DNA fragment
      being detected at all concentrations. However, in marked contrast to this, JM335
      failed to cause apoptosis at 10 x IC50, the detached cells neither displaying
      apoptotic morphology nor a detectable 50 kb DNA fragment. Moreover, these
      detached cells showed evidence of extensive vesiculation while the DNA remained
      normal in appearance and thus appeared to have died by a non-apoptotic mode.
      Apoptosis also appeared to be induced to a lesser extent at 5 x IC50 of JM335 as
      demonstrated by a less intense 50 kb fragment compared with that seen at 2 x
      IC50. The main cell cycle effect of these drugs (at 2 x IC50) was a slowdown in S
      phase traverse during which most but not all of the apoptosis appeared to occur.
      However, at 5 x IC50 of JM335 cells appeared frozen in all phases of the cell
      cycle with little progress from G1 to S accompanied by a build-up of cells in G2
      indicative of a G2/M block. This difference in cell cycle effect may account for
      the reduced level of apoptosis at this concentration and a failure to engage
      apoptosis at higher concentrations. These data suggest that the nature of the
      platinum drug (and consequently, the nature of resultant DNA damage) may have
      important implications in determining the rate and mechanism of cell death in
      this cell line. The cell death effects observed with the trans complex JM335 may
      correlate with the induction of DNA single-strand breaks in this cell line.

PMID- 8855972
TI  - Quantitative analysis of multidrug resistance gene expression in human
      osteosarcomas.
AB  - We evaluated the MDR1 expression levels in 77 osteosarcomas and investigated
      whether MDR1 mRNA expression in osteosarcomas varies with location within the
      tumour, following chemotherapy, or after metastasis. We modified the
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assay
      to determine accurately the levels of MDR1 mRNA expression in clinical specimens.
      We show that specimens collected from multiple locations in six tumours revealed
      very little variation in MDR1 expression suggesting that the levels of MDR1 in
      these tumours do not vary greatly with location within the tumour mass. In a
      comparison of pre and post-chemotherapy specimens it was found that MDR1 levels
      did not change appreciably following chemotherapy in 16 of 20 cases. In addition,
      in eight of ten specimens obtained before and after metastasis, the amount of
      MDR1 mRNA was found to remain relatively constant despite metastatic spread.
      Thus, many osteosarcomas exhibited intrinsic expression of MDR1 mRNA before
      multidrug regimens which invariably included doxorubicin and, in most cases, MDR1
      expression was not induced following chemotherapeutic treatment. Our results
      suggest that some osteosarcoma patients may have primary tumours which are
      resistant to doxorubicin. These individuals may benefit from different
      chemotherapeutic regimens, e.g. the addition of MDR reversal agents.

PMID- 8855973
TI  - Codon 12 Ki-ras mutation in non-small-cell lung cancer: comparative evaluation in
      tumoural and non-tumoural lung.
AB  - Ki-ras activation by point mutation on codon 12 has been reported in non-small
      cell lung carcinomas and in various models of experimental lung tumours induced
      by chemical carcinogens. The cellular targets for carcinogenic compounds of
      tobacco smoke are usually considered to be the cells of the bronchial mucosa or
      alveolar epithelium. However, little is known about preneoplastic events in
      bronchopulmonary carcinogenesis. The hypothesis of the presence of widespread
      target cells containing Ki-ras mutation was investigated by evaluating concurrent
      neoplastic and non-neoplastic bronchial and alveolar samples from 51 patients
      with non-small-cell lung carcinomas. The polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method used can detect one cell with a
      mutation on codon 12 among 10(2) normal cells. In tumour samples, a mutation was
      detected in 20% of adenocarcinomas, but in none of the adenosquamous or squamous
      cell carcinomas. No mutation was detected in the non-neoplastic bronchial or
      parenchymal samples. When using an enriched PCR-RFLP method detecting one mutated
      allele among 10(3) normal alleles a mutation was detected in 23% of
      adenocarcinomas. In conclusion, Ki-ras activation by mutation on codon 12 was not
      observed in non-neoplastic bronchial or parenchymal tissues in patients with
      bronchopulmonary cancers and does not appear to be a genetic event present in non
      malignant epithelial target cells exposed to tobacco smoke.

PMID- 8855974
TI  - Anomalous retinoblastoma protein expression in Sternberg-Reed cells in Hodgkin's
      disease: a comparative study with p53 and Ki67 expression.
AB  - Retinoblastoma (Rb) tumour-suppressor protein plays a critical role in cell cycle
      control. Rb inactivation is a frequent phenomenon in tumours of different cell
      lineages, in which the absence of Rb protein has been considered to be a marker
      of Rb disregulation. We used modern immunohistochemical techniques to study the
      expression of Rb protein in a large series of 130 patients with Hodgkin's
      disease. Simultaneously, Western blot was used to analyse a more restricted group
      (12 patients) to confirm the immunohistochemical results and to clarify the
      phosphorylation status of Rb protein. As the level of Rb expression varied
      according to cell cycle stage, we also performed immunostaining for Ki67, a
      protein present in proliferating cells. To make comparison possible, we first
      characterised the amount and phosphorylation status of Rb protein in reactive
      lymphoid tissue and phytohaemagglutinin (PHA)-stimulated lymphocytes. The
      presence of p53 in Sternberg-Reed cells was also included in the study, as both
      proteins (p53 and Rb) have been found to be closely associated in cell cycle
      control. PHA-stimulated peripheral blood lymphocytes showed a parallel increase
      in Rb and cell cycle progression, together with progressive Rb phosphorylation.
      In reactive lymphoid tissue there was also a clear correlation between Rb
      expression and the Ki67 proliferation index (R = 0.96, P = 0.038). When analysing
      Hodgkin's disease samples, a clear difference emerges between cases of nodular
      lymphocyte predominance, which preserve the relationship between Rb and Ki67
      expression (r = 0.8727, P = 0.000), and classical forms of Hodgkin's disease
      (nodular sclerosis and mixed cellularity), which display a strong deviation from
      this pattern. Two main anomalies were found: (1) One group of 21/130 cases with
      partial or total loss of Rb protein expression, which could reflect the existence
      of genetic alterations, or an altered transcriptional or translational regulation
      of Rb gene. (2) Another group with an abnormally high Rb/Ki67 ratio, which could
      support conflicting interpretations: (i) excess Rb protein for controlling cell
      cycle progression; or (ii) adhesion of Rb protein to other cellular or viral
      proteins, such as p53 and MDM2. The results of this study indicate an anomalous
      pattern of expression of Rb in classical forms of Hodgkin's disease, and suggest
      the possibility of undertaking functional studies (E1A adhesion, p16 expression)
      with the aim of better characterising the status of Rb protein, and correlating
      these findings with clinical course in Hodgkin's disease patients.

PMID- 8855975
TI  - Nm23 expression in endometrial and cervical cancer: inverse correlation with
      lymph node involvement and myometrial invasion.
AB  - The expression of nm23 has been shown to correlate in some solid tumours with
      their metastatic potential and to be associated with a favourable prognosis in
      human breast cancer and melanoma. In breast and ovarian cancer nm23 expression is
      also correlated with lymph node involvement. We analysed the expression of nm23
      H1 and -H2 in normal endometrium and in endometrial and cervical cancer by both
      Northern and Western blotting. Cellular localisation of Nm23-H1 was visualised by
      immunohistochemistry mostly in the cytoplasm. Both isoforms of Nm23 were present
      in all the samples analysed, and a clear direct correlation between Nm23-H1 and 
      H2 levels was evident. Median nm23-H2 levels were higher than than -H1 levels in
      both tissues. Cervical cancer patients with lymph node involvement were shown to
      have significantly lower protein levels of Nm23 (P < 0.007 for H1 and P < 0.009
      for H2), and a similar trend was also evident in endometrial cancer. Furthermore,
      the degree of myometrial invasion in endometrial cancer patients was also
      inversely correlated with Nm23-H1 levels of expression (P < 0.003). Nm23 level
      may therefore be taken into consideration as a new marker in the prognostic
      characterisation and in the treatment planning of uterine tumour patients.

PMID- 8855976
TI  - Sporadic CDKN2 (MTS1/p16ink4) gene alterations in human ovarian tumours.
AB  - The cell cycle regulatory proteins p16 and p21 cause cell cycle arrest at the G1
      checkpoint by inhibiting activity of cyclin D-CDK4 complexes. The TP53 gene,
      regulating the p21 protein, is mutated at high frequency in ovarian cancer. The
      CDKN2 gene, encoding the p16 protein, has been mapped to chromosome 9p21 and
      encompasses three exons. To establish the frequency of CDKN2 gene abnormalities
      in ovarian tumour specimens, we have studied this gene in five ovarian cancer
      cell lines and in 32 primary and five metastatic ovarian adenocarcinomas. Using
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and
      sequencing techniques both exon 1 and 2 of the CDKN2 gene, encompassing 97% of
      the coding sequence, were analysed. In addition, the TP53 gene was studied for
      the presence of mutations. The cell line HOC-7 showed a 16 bp deletion in exon 2
      of the CDKN2 gene, resulting in a stop codon, whereas in cell line SK-OV-3 this
      gene was found to be homozygously deleted. Nine primary tumour specimens showed a
      migration shift on SSCP. Sequencing revealed a common polymorphism (Ala148Thr) in
      seven of these ovarian tumour specimens. The two other tumour samples were found
      to contain silent mutations, one at codon 23 (GGT-->GGA) and the other at codon
      67 (GGC-->GGT). Mutations in the TP53 gene were observed in 46% of the ovarian
      tumour specimens. We conclude that CDKN2 gene alterations are rare events in
      human ovarian cancer. The low prevalence of these alterations do not allow for
      analysis of an association of this gene with prognosis.

PMID- 8855977
TI  - Dysregulation of autocrine TGF-beta isoform production and ligand responses in
      human tumour-derived and Ha-ras-transfected keratinocytes and fibroblasts.
AB  - This study examined the autocrine production of TGF-beta 1, -beta 2 and -beta 3
      in culture supernatants from tumour-derived (H series, n = 7; BICR series, n =
      5), Ha-ras-transfected (n = 4) and normal (n = 2) human keratinocytes using a
      sandwich enzyme-linked immunosorbent assay (ELISA). Detection limits were 39.0 pg
      ml-1 for TGF-beta 1, 78.0 pg ml-1 for TGF-beta 2 and 1.9 ng ml-1 for TGF-beta 3.
      Tumour-derived oral keratinocytes predominantly produced less TGF-beta 1 than
      normal oral epithelial cells; the expression of endogenous TGF-beta 2 was
      variable. In keratinocytes containing mutant Ha-ras, TGF-beta 1 production was
      enhanced and TGF-beta 2 was undetectable. TGF-beta 3 mRNA was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) but the protein was not detected
      in conditioned media, most probably because of the low detection limits of the
      ELISA for this isoform. Neutralisation experiments indicated that the latent TGF
      beta peptide was secreted in keratinocyte conditioned medium. Seven tumour
      derived keratinocyte cell lines (H series) and fibroblasts separated from normal
      (n = 1) and tumour-derived (n = 2) keratinocyte cultures were examined for their
      response to exogenous TGF-beta 1, -beta 2 and -beta 3. Six of seven tumour
      derived keratinocyte cell lines were inhibited by TGF-beta 1 and TGF-beta 2 (
      beta 1 > -beta 2); one cell line was refractory to both TGF-beta 1 and TGF-beta
      2. Keratinocytes were inhibited (4 of 7), stimulated (1 of 7) or failed to
      respond (2 of 7) to TGF-beta 3, TGF-beta 1, -beta 2 and -beta 3 stimulated both
      normal and tumour-associated fibroblasts, but the tumour-associated fibroblasts
      showed less response to the ligands than their normal counterparts following
      prolonged treatment with each isoform. The results demonstrate variable autocrine
      production of TGF-beta isoforms by malignant keratinocytes, with loss of TGF-beta
      1 generally associated with the tumour-derived phenotype and modification of
      endogenous isoform production dependent on the genetic background of the tumour
      cells. Further, the variable response of the tumour-derived keratinocytes and
      contiguous fibroblasts to the TGF-beta isoforms suggests that dysregulation of
      TGF-beta autocrine and paracrine networks are common characteristics of squamous
      epithelial malignancy.

PMID- 8855978
TI  - Different hCG assays to measure ectopic hCG secretion in bladder carcinoma
      patients.
AB  - We evaluated the clinical performance of assays measuring intact human chorionic
      gonadotropin alone (i-hCG), intact and nicked human chorionic gonadotropin (i-hCG
      and hCGn), free beta-subunit (free beta-hCG) and total beta-human chorionic
      gonadotropin (t-hCG) using different commercial kits, in a group of bladder
      carcinoma patients with ectopic human chorionic gonadotropin (hCG) secretion, at
      diagnosis and during treatment. The diagnostic sensitivity obtained ranged
      between 63.6% and 75.7% (t-hCG assays), 72.7% (free beta-hCG assay), 18.2% (i-hCG
      and hCGn) and 6% (i-hCG assay). Median increases of hCG during treatment in
      patients with chemotherapy resistance ranged from 4.9 to 6.9 for t-hCG and free
      beta-hCG assays and from 1.4 to 3.2 for i-hCG and i-hCG plus hCGn assays. Median
      decreases when chemotherapy was efficient ranged from 2.8 to 3.3 (t-hCG and free
      beta-hCG assays) and from 1.1 to 1.5 (i-hCG and i-hCG plus hCGn assays). We
      conclude that t-hCG and free beta-hCG are the most suitable assays for the
      management of bladder carcinoma patients as the ectopic secretion of chorionic
      gonadotropin is mainly due to the free beta-subunit.

PMID- 8855979
TI  - Clonal and functional analysis for the augmentation of tumour-infiltrating
      lymphocytes by interleukin 4.
AB  - In the adoptive immunotherapy for cancer, the amounts of induced effector cells
      play a major role in improving therapeutic efficacy. We have already demonstrated
      that interleukin 4 (IL-4) augments proliferation of tumour-infiltrating
      lymphocytes (TILs) without altering the cytotoxic activity against autologous
      tumour cells. The present study is designed to investigate how IL-4 augments TILs
      by using established TIL clones in terms of IL-2/IL-2 receptor system. CD4+, CD8+
      and CD4+ CD8+ (double positive) TIL clones were established from cancer patients.
      At clonal level, IL-4 augmented the proliferation of IL-2-activated TIL clones
      irrespective of phenotypes. In order to clarify the mechanism of IL-4 at clonal
      level, the blocking assay by anti-IL-2 receptor alpha and beta chain and binding
      assay of IL-2 on the cell surface and the measurement of the internalisation of
      IL-2 in the cell were performed. It was clarified that IL-4 up-regulated the IL-2
      receptor and then augmented the action of IL-2 molecule on the cell surface
      stimulated by IL-4. Furthermore, binding IL-2 internalised rapidly into the
      cells. Thus, it is suggested that signal transduction is augmented and
      proliferation of TILs is enhanced by IL-4 via the action of IL-2/IL-2 receptor
      system.

PMID- 8855980
TI  - Molecular design of hybrid tumour necrosis factor-alpha. II: The molecular size
      of polyethylene glycol-modified tumour necrosis factor-alpha affects its anti
      tumour potency.
AB  - To design hybrid tumour necrosis factor-alpha (TNF-alpha) applicable to systemic
      anti-tumour therapeutic use, we assessed the relationships among the molecular
      size of hybrid TNF-alpha, in vitro bioactivity and in vivo anti-tumour potency.
      Natural human TNF-alpha was covalently modified with polyethylene glycol (PEG) of
      various number-average molecular weights (Mn = 2000, 5000, 12,000). The in vitro
      bioactivity of PEG-modified TNF-alpha s decreased with an increase in the degree
      of PEG modification, irrespective of the molecular weight of PEG. This decrease
      in the specific bioactivity markedly increased with an increase in the molecular
      weight of the attached PEG. The in vivo anti-tumour effects of the hybrid TNF
      alpha s with a molecular size from 100 to 110 kDa, which had more than 50% of
      specific bioactivity of native TNF-alpha, were significantly superior to other
      PEG-TNF-alpha s. These hybrid TNF-alpha s showed over ten times greater anti
      tumour effects than native TNF-alpha. Thus, the molecular size, which was
      determined by the degree of PEG modification and PEG molecular weight, influences
      the specific activity and anti-tumour effects of hybrid TNF-alpha.

PMID- 8855981
TI  - Differential responses of scirrhous and well-differentiated gastric cancer cells
      to orthotopic fibroblasts.
AB  - Scirrhous gastric cancer cells proliferate rapidly with fibrosis, when the cancer
      cells invade into the submucosa of the stomach. To investigate the mechanisms
      responsible for the rapid proliferation, the growth interaction between gastric
      cancer cells and fibroblasts was examined. Human gastric cancer cell lines
      established from scirrhous carcinoma or well-differentiated adenocarcinoma were
      used. Human fibroblast cell lines were obtained from various organs. The growth
      interaction between gastric cancer cells and fibroblasts was examined by
      calculating the number of cancer cells or by measuring [3H]thymidine
      incorporation of cancer cells. Gastric fibroblasts specifically stimulated the
      growth of scirrhous gastric cancer cells, but not that of well-differentiated
      adenocarcinoma cells. The growth factor(s) produced from gastric fibroblasts were
      then partially purified and characterised. The growth-promoting factor(s) had
      apparent molecular weights of 10000 dalton and was sensitive both to heat and
      proteinase treatment. No inhibition for the factor(s) was achieved with defined
      anti-growth factor antibodies. In this study, differential responses of scirrhous
      and well-differentiated gastric cancer cells to orthotopic fibroblasts were
      shown. Rapid proliferation of scirrhous gastric carcinoma should be partly
      controlled by orthotopic fibroblasts. The growth factor(s) from gastric
      fibroblasts, which was distinct from various defined growth factors such as
      epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF),
      transforming growth factor-alpha (TGF-alpha), keratinocyte growth factor (KGF),
      vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-I),
      hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and
      transforming growth factor beta 1 (TGF-beta 1) may play an important role in the
      progression of scirrhous gastric cancer cells.

PMID- 8855982
TI  - Infrequent alterations of the APC and MCC genes in gastric cancers from British
      patients.
AB  - We examined 26 gastric carcinomas from British patients for mutations of the APC
      gene using a single-strand conformation polymorphism (SSCP) and heteroduplex
      assay in conjunction with the protein truncation test (PTT). In addition, we
      performed loss of heterozygosity (LOH) analysis of the APC and MCC genes. We
      detected an inactivating somatic mutation in one gastric tumour. LOH of APC was
      observed in one of 12 informative cases (8%) and of MCC in two of 20 cases (10%).
      We thus find that alteration of the APC and MCC genes are infrequent in gastric
      cancers from the British population. Tumour-suppressor genes on other chromosomes
      must play a more significant role in the development of these tumours.

PMID- 8855983
TI  - A randomised dose escalation study of subcutaneous interleukin 2 with and without
      levamisole in patients with metastatic renal cell carcinoma or malignant
      melanoma.
AB  - We have examined the efficacy, toxicity and host immunological response of two
      different dose schedules of interleukin 2 (IL-2) given subcutaneously, daily for
      3 months in patients with renal cell carcinoma (RCC) or metastatic melanoma (MM).
      We also examined the effect of adding the immune modulator levamisole to the two
      different schedules of IL-2. Thirty-nine patients were entered into two
      sequential phase I/II studies. Eighteen patients entered study 1 and were
      randomised to receive IL-2, 3 x 10(6) IU m-2 day-1, subcutaneously for 3 months
      with or without levamisole 50 mg t.d.s. p.o. on days 1-3 on alternate weeks.
      Twenty-one patients entered study 2 and were randomised to receive 5.4 x 10(6) IU
      m-2 day-1 subcutaneously for 3 months with or without levamisole 50 mg t.d.s.
      p.o. on days 1-3 on alternate weeks. Blood was taken for peripheral blood
      lymphocyte (PBL) phenotype analysis, and measurement of IL-2, soluble IL-2
      receptor (sIL-2R) and neopterin concentration. Two patients with metastatic
      melanoma, one in each study, responded (11.8%); both received IL-2 alone.
      Observations of immunological parameters showed that treatment with subcutaneous
      IL-2 resulted in a significant rise in the percentage of PBLs bearing CD25,
      CD3/HLA-DR, CD56 and levels of IL-2 receptor and neopterin. The total white blood
      cell count (WBC) and total lymphocyte count rose significantly on day 18 compared
      with pretreatment levels. The addition of levamisole to either IL-2 schedule
      resulted in no significant changes in any immunological parameters. This study
      illustrates that prolonged subcutaneous IL-2 can be given safely in the
      outpatient setting. There was no evidence that levamisole acts as an
      immunomodulator in this study.

PMID- 8855984
TI  - Impact of tumour burden on chemotherapy-induced nausea and vomiting.
AB  - We investigated how residual tumour burden after cytoreductive surgery was
      related to the occurrence of acute and delayed nausea and vomiting in 101 ovarian
      cancer patients receiving their first chemotherapy course. The anti-emetic
      treatment included ondansetron combined with dexamethasone or placebo. After
      chemotherapy all patients received ondansetron only for 5 days. Two categories of
      tumour burden (TB) were formed according to the diameter of the greatest residual
      tumour (< 2 cm = minimal TB and > or = 2 cm = large TB). Self-reports of nausea
      and vomiting were obtained for 15 days. Other potential predictor variables were
      assessed and included in multivariate analyses. Patients with large compared with
      minimal TB had more delayed emesis, especially on days 2-7. They also had more
      acute nausea. The aggravating effect associated with large residual TB was more
      evident in patients > or = 55 years. During the second week after the
      chemotherapy the occurrence of nausea was higher in patients > or = 55 years than
      in those < 55 years. This was seen primarily in patients with large residual TB.
      Predictors for no delayed emesis at all were anti-emetic treatment with
      dexamethasone, minimal tumour burden, low neuroticism and no history of motion
      sickness. The increased risk of "persistent' delayed nausea and vomiting seen in
      older patients with large tumour burden may have important clinical implications
      and warrants further attention.

PMID- 8855985
TI  - pS2 protein: a marker improving prediction of response to neoadjuvant tamoxifen
      in post-menopausal breast cancer patients.
AB  - Tamoxifen as sole initial therapy is gaining importance in the management of post
      menopausal breast cancer patients. Age oestrogen (ER) and progesterone (PR)
      receptor status are accurately considered to select patients for hormonal
      treatment. However, additional markers are needed. By immunohistochemistry (IHC),
      we studied tumour expression of ER, PR, pS2, c-erbB-2 and glutathione S
      transferase pi (GST pi) on initial core biopsies of 208 post-menopausal patients
      with a non-metastatic invasive ductal carcinoma, treated by neoadjuvant tamoxifen
      therapy. A good response to tamoxifen was defined as tumoral regression > or =
      50% (110 patients). Relationship between response and age, tumour size, T, N,
      histological grade, ER and PR contents evaluated by radioimmunoassay, ER, PR,
      pS2, c-erbB-2 and GST pi expression evaluated by IHC were studied. Univariate and
      multivariate analysis showed that tumoral regression was linked only to pS2 (P =
      0.004) and ER (P = 0.018) IHC expression. According to the immunohistochemical
      profile, three groups could be defined: pS2- and ER-positive tumours, pS2- or ER
      positive tumours and pS2- and ER-negative tumours with response rates of 60%, 45%
      and 8% respectively. Although prospective studies are needed to confirm these
      results, we conclude that pS2 and ER immunohistochemical status are useful tools
      for predicting tumour regression with neoadjuvant tamoxifen in post-menopausal
      breast carcinoma patients.

PMID- 8855986
TI  - Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence
      in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3.
AB  - To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3
      in the early diagnosis of recurrence, serial serum determinations of these
      antigens were performed in 200 patients (follow-up 1-4 years, mean 2.2 years)
      with primary breast cancer and no evidence of residual disease (NED) after
      radical treatment (radical mastectomy or simple mastectomy and radiotherapy).
      Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA
      15.3 were elevated (> 20 U ml-1, > 10 ng ml-1 or > 60 U ml-1 respectively) before
      diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead
      time of 4.5 +/- 2.4, 4.9 +/- 2.4 and 4.8 +/- 2.4 months respectively. Tumour
      marker sensitivity was clearly related to the site of recurrence, with the lowest
      sensitivity found in locoregional relapse and the highest in patients with liver
      metastases. When patients with locoregional recurrences were excluded,
      sensitivity improved: 31% (c-erbB-2), 33% (CEA) and 56% (CA 15.3), with 76%
      having at least one of the three tumour markers. C-erbB-2 sensitivity in early
      diagnosis was significantly higher in patients with c-erbB-2 overexpression in
      tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P =
      0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of
      recurrence, higher sensitivity in early diagnosis of relapse and a higher lead
      time were found in PR+ patients (CA 15.3, P < 0.0001) or in PR- patients (c-erbB
      2, P = 0.009). Specificity of the tumour markers was 100% for all three markers
      (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis
      of metastases, mainly in those patients with c-erbB-2 overexpression in tissue.
      Using all three markers simultaneously it is possible to increase the sensitivity
      in the early diagnosis of recurrence by 11.2%.

PMID- 8855987
TI  - Continuous infusion or subcutaneous injection of granulocyte-macrophage colony
      stimulating factor: increased efficacy and reduced toxicity when given
      subcutaneously.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a haematopoietic
      growth factor with a wide variety of applications in the clinic. In early phase I
      studies the continuous intravenous (c.i.) route of administration was often used.
      Later it was shown that subcutaneous (s.c.) administration was also effective.
      The optimal route of administration remains, however, poorly defined, and no
      studies have made a direct comparison between these two routes of administration.
      We treated patients with advanced breast cancer with moderately high-dose
      doxorubicin and cylophosphamide and GM-CSF. The first 14 patients received GM-CSF
      by c.i, while subsequently 47 patients received it s.c. Comparison between the
      two groups showed that c.i. GM-CSF was more toxic in several respects. There was
      a higher need for erythrocyte and platelet transfusions and a significant
      deterioration in the performance status. This study indicates that subcutaneous
      GM-CSF is the preferred route of administration. Randomised trials are, however,
      needed to confirm these conclusions.

PMID- 8855988
TI  - 5-Hydroxyindoleacetic acid (5-HIAA) and cortisol excretion as predictors of
      chemotherapy-induced emesis.
AB  - This study evaluated the relationship between prechemotherapy cortisol and 5
      hydroxyindoleacetic acid (5-HIAA) excretion and chemotherapy-induced emesis. The
      urinary excretion of cortisol and the serotonin metabolite 5-HIAA in the night
      before chemotherapy administration were measured in 28 and 49 female patients
      receiving > 300 mg m-2 carboplatin. Vomiting and nausea were documented over a 3
      day observation period. Lower basal cortisol excretion was significantly
      correlated with vomiting with or without nausea occurring within the observation
      period. 5-HIAA showed only a weak correlation with emesis on days 1-3, but low 5
      HIAA excretion was correlated with a higher proportion of patients vomiting on
      days 2-3 following chemotherapy. Low basal cortisol excretion might be useful as
      a predictor for chemotherapy-induced emesis and therefore should be evaluated
      prospectively in future studies.

PMID- 8855989
TI  - Phase I study of simultaneous dose escalation and schedule acceleration of
      cyclophosphamide-doxorubicin-etoposide using granulocyte colony-stimulating
      factor with or without antimicrobial prophylaxis in patients with small-cell lung
      cancer.
AB  - A phase I study was designed to assess whether dose intensity of an 'accelerated'
      cyclophosphamide-doxorubicin-etoposide (CDE) regimen plus granulocyte colony
      stimulating factor (G-CSF) could be increased further, in an outpatient setting,
      by escalating the dose of each single drug of the regimen. Patients with
      previously untreated small-cell lung cancer (SCLC) received escalating doses of
      cyclophosphamide (C) 1100-1300 mg m-2 intravenously (i.v.) on day 1, doxorubicin
      (D) 50-60 mg m-2 i.v. on day 1, etoposide (E) 110-130 mg m-2 i.v. on days 1, 2, 3
      and every 14 days for at least three courses. Along with chemotherapy, G-CSF
      (filgastrim) 5 micrograms kg-1 from day 5 to day 11 was administered
      subcutaneously (s.c.) to all patients. Twenty-five patients were enrolled into
      the study. All patients at the first dose level (C 1100, D 50, E 110 x 3)
      completed three or more cycles at the dose and schedule planned by the protocol
      and no 'dose-limiting toxicity' (DLT) was seen. At the second dose level (C 1200,
      D 55, E 120 x 3) three out of five patients had a DLT consisting of
      'granulocytopenic fever' (GCPF). Another six patients were treated at this dose
      level with the addition of ciprofloxacin 500 mg twice a day and only two patients
      had a DLT [one episode of documented oral candidiasis and one of 'fever of
      unknown origin' (FUO) with generalised mucositis]. Accrual of patients proceeded
      to the third dose level (C 1300, D 60, E 130 x 3) with the prophylactic use of
      ciprofloxacin. Four out of six patients experienced a DLT consisting of GCPF or
      documented non-bacterial infection. Accrual of patients at the third dose level
      was then resumed adding to ciprofloxacin anti-fungal prophylaxis (fluconazole 100
      mg daily) and anti-viral prophylaxis (acyclovir 800 mg twice a day) from day 5 to
      11. Out of five patients treated three experienced a DLT consisting of severe
      leucopenia and fever or infection. With a simultaneous dose escalation and
      schedule acceleration it is indeed possible to take maximum advantage of G-CSF
      activity and to increase CDE dose intensity by a factor 1.65-1.80 for a maximum
      of 3-4 courses. The role of antimicrobial prophylaxis in this setting deserves to
      be investigated further.

PMID- 8855990
TI  - Birth characteristics and risk of Wilms' tumour: a nationwide prospective study
      in Norway.
AB  - Relationships between incidence of Wilms' tumour and information recorded at
      birth were investigated in a prospective study of the 1,489,297 children born in
      Norway between 1967 and 1992. A total of 119 individuals were diagnosed with
      Wilms' tumour in the age interval 0-14 years. A high length at birth was
      significantly associated with a high risk (incidence rate ratio 1.8 for length >
      or = 53 cm vs < or = 49 cm, 95% CI 1.0-3.2). A low Apgar score at 1 min was also
      associated with an increased risk (incidence rate ratio 2.2 for Apgar score < or
      = 8 vs a score > or = 9, 95% CI 1.2-3.9). For all variables for which an
      association was indicated, the association seemed to be restricted mainly to
      children aged less than 2 years. This suggests that Wilms' tumour diagnosed early
      in life may differ aetiologically from that of cases diagnosed later.

PMID- 8855991
TI  - Weight loss precedes dementia in community-dwelling older adults.
AB  - OBJECTIVE: To determine whether the weight loss associated with Alzheimer's
      disease precedes or follows the dementia. DESIGN: Older community-dwelling men (n
      = 134) and women (n = 165) were followed for 20 years before they were diagnosed
      as cognitively intact or demented. A repeated measures analysis was used to
      compare weight change in those who developed Alzheimer's Disease (AD) with those
      who remained cognitively intact. MEASUREMENTS: Weight was measured at three
      clinic visits between 1972-74, 1984-87, and 1990-93. Participants were classified
      as having probable or possible AD or being cognitively intact at the 1990-93
      evaluation. Diagnoses were made by two neurologists and a neuropsychometrist,
      based on neuropsychological tests and physical examination, using NINCDS-ADRDA
      criteria. RESULTS: There were 36 men and 24 women diagnosed with probable or
      possible AD; they were considered to have mild to moderate dementia based on
      their test scores and community-dwelling status. Those who developed dementia
      were older than those diagnosed as cognitively intact. In age-adjusted analyses,
      both men and women who were later diagnosed with AD had a significant decrease in
      weight after the baseline visit (P < .001 and P < .003, respectively), but there
      was no significant weight loss in the men and women who remained cognitively
      intact. These differences were not explained by lifestyle, depression, or other
      illness. CONCLUSION: Weight loss precedes mild to moderate dementia; early weight
      loss is, therefore, unlikely to be a consequence of AD patients being unable or
      unwilling to eat.

PMID- 8855992
TI  - Sequential outbreak of influenza A and B in a nursing home: efficacy of vaccine
      and amantadine.
AB  - OBJECTIVE: To describe the sequential occurrence of influenza A and B in a
      nursing home, and to determine the efficacy of influenza vaccine and/or
      amantadine treatment with respect to incidence and sequelae. SETTING: The Jewish
      Home and Hospital for Aged, a skilled-care nursing facility. PARTICIPANTS: Of 499
      frail older nursing home residents, 139 contracted influenza during the study
      period (mean age 87.5 years; SD = 6.7). The residents were followed from February
      through April 1988. INTERVENTION: Influenza vaccine and/or amantadine.
      MEASUREMENTS: Episodes of influenza and their sequelae, i.e., pneumonia,
      hospitalization, and death. RESULTS: The vaccine had no effect on the incidence
      of influenza-like illness, length of illness, or the associated death rate. It
      reduced the rate of pneumonia secondary to influenza A and B (relative risk =
      .57; 95% CI: .37 to .89; P = .023). Amantadine did not affect the attack rate of
      influenza nor the rate of pneumonia secondary to influenza. It was associated
      with decreased mortality (relative risk = 0; P = .001), and shorter length of
      influenza A illness (PWilcoxon = .082). Although the combination of amantadine
      and vaccine did not affect length of influenza (A or B) illness, it was
      associated with a significantly lower rate of sequelae (relative risk = .58; 95%
      CI: .36 to .95; P = .024). CONCLUSION: In this epidemic, the combination of
      amantadine and vaccine was most effective in reducing the rate of influenza
      associated sequelae. The possibility of a "biphasic" epidemic prompts
      consideration of vaccinating nonimmunized nursing home residents, even though it
      may be late in the influenza season.

PMID- 8855993
TI  - The relationship between alcohol consumption, cognitive performance, and daily
      functioning in an urban sample of older black Americans.
AB  - OBJECTIVE: To report on moderate alcohol consumption and measurements of
      cognitive function and activities of daily living in an older, urban, community
      dwelling sample of black Americans. DESIGN: As part of a community prevalence
      study of dementia, information on alcohol consumption and cognitive performance
      was collected on 2040 randomly selected black subjects living in Indianapolis.
      MEASUREMENTS: From questions in the screening interview, alcohol consumption was
      grouped into four categories: lifetime abstainers, regular drinkers less than 4
      drinks per week, 4 to 10 drinks per week, and more than 10 drinks per week.
      Current and past drinkers were analyzed separately. Three measurements were used:
      (1) a total cognitive score; (2) the delayed recall score from the East Boston
      Memory Test; (3) a score for daily functioning based upon information from the
      informant. Multiple regression models were fitted with drinking variables as the
      major predictor, including covariates of age, gender, education, history of
      stroke, hypertension, being treated for depression, and a family history of
      dementia. MAIN RESULTS: In all analyses, there was a very consistent pattern for
      both current and past drinkers. There was a small but significant dose effect of
      drinking for the drinkers, with subjects in the heaviest drinking category
      scoring poorest, i.e., lowest scores in cognitive tests and highest scores in
      scales of daily functioning indicating more impairment. The scores of abstainers
      were worse than those of subjects in the lightest drinking category. The pattern
      of scores for cognitive performance and daily functioning was similar between
      current and past drinkers. These patterns remained the same even after potential
      confounders were included. CONCLUSIONS: Previous research on effects of alcohol
      on health indices have suggested a J-shaped relationship between amounts of
      alcohol consumption and measurements of heart disease, stroke, and mortality
      rates. Our study provides some support for the concept of a similar J-shaped
      relationship between cognitive performance and alcohol consumption, but the
      differences between drinking categories were modest and the clinical significance
      of these findings uncertain.

PMID- 8855994
TI  - Inner-city older blacks have high levels of functional disability.
AB  - OBJECTIVES: To describe the frequency and severity of functional problems in two
      groups of noninstitutionalized inner-city blacks aged 70 years and older
      contrasted with results from appropriate groups of white and black older adults
      and with the goals of the Healthy People 2000 program. DESIGN: Cross-sectional
      descriptive study. SETTING: Community-based samples. PARTICIPANTS: A population
      based sample of 416 older adults living in a 3.5-square mile catchment area in
      north St. Louis (NSL), Missouri, and a sample of 197 older residents living in
      public housing in East St. Louis (ESL), Illinois. MEASUREMENTS: Health status,
      preventive health activities, health services utilization, and risks for
      progressive frailty were assessed by self report and observation using well
      validated, standardized instruments. Whenever possible, comparison data were
      derived from national datasets, original samples used to validate the measures,
      and other useful comparison groups. RESULTS: The NSL sample had somewhat better
      health status and risk for progressive disability than the ESL sample. However,
      compared with national or regional reference groups using age-gender adjustments,
      both study groups demonstrated increased levels of dependence in intermediate
      activities of daily living, restricted activity days, inability to walk one-half
      mile without assistance, reported poor vision, living alone, and limited income
      compared with both older whites and blacks, and increased levels of worsening
      health, inability to perform heavy work around the house, never walking a mile or
      more, and currently unmarried versus whites with variable decrements versus
      blacks. Contrasted with other comparison groups, the two samples had increased
      body fat; consistent decrements in gait speed, timed chair stands, timed one-leg
      balance, and frequency of preventive exercise; and lower levels of dental care;
      results relative to physician visits and hospital days were mixed. They also had
      high levels of measured visual and hearing impairments, unmet needs for home
      delivered meals, and problems with false teeth. Deficiencies compared with the
      goals of Healthy People 2000 were large. CONCLUSIONS: The special attributes of
      inner-city blacks, including poverty and access to and acceptance of remedial
      programs, will have to be considered if the goals of Healthy People 2000 are to
      be met in this important and growing segment of older Americans. 44:0000-0000,
      1996.

PMID- 8855995
TI  - Sex differences in survival after myocardial infarction in older adults: a
      community-based approach.
AB  - OBJECTIVE: To determine sex differences in survival after myocardial infarction
      in older individuals. DESIGN: Prospective cohort study based on a community
      sample of older individuals. All patients were followed for 1 year after hospital
      admission. SETTING: Two hospitals in New Haven, Connecticut. PARTICIPANTS: The
      study included 103 women and 120 men who were participants in the New Haven, CT
      cohort of the Established Populations for the Epidemiologic Study of the Elderly
      (EPESE) program and who were diagnosed with myocardial infarction between the
      inception of the community study in 1982 and December 31, 1992. The mean age of
      women was 79.3 and of men, 77.3. MEASUREMENTS: Data on clinical characteristics
      were abstracted from medical records. Sociodemographic, psychosocial, and
      physical function information was derived from the EPESE interview preceding the
      infarction. The main outcome measure was all-cause mortality, for which three end
      points were used: early mortality (first 30 days), late mortality (1-year
      mortality among survivors of the first 30 days), and overall mortality (1-year
      mortality from admission in the whole sample). RESULTS: Mortality in the first 30
      days did not differ significantly in the two sexes. The relative risk (RR) of
      death in women compared with men was 0.85 (95% confidence interval [CI], 0.49
      1.47) before multivariable adjustment; this was unchanged after adjustment for
      demographic factors, comorbidity, functional status, psychosocial factors, and
      clinical severity (RR, 0.85, 95% CI, 0.41-1.76). Among survivors of 30 days,
      women were almost two times more likely to survive at 1 year compared with men,
      both before multivariable adjustment (RR, 0.56, 95% CI, 0.31-1.02) and after
      controlling for demographic factors, comorbidity, physical function, psychosocial
      factors, clinical severity on admission, and hospital complications (RR, 0.44 ;
      95% CI, 0.20-0.99). Analyses involving 1-year follow-up from admission for the
      entire sample yielded intermediate results. CONCLUSION: There was little
      difference in mortality in the first 30 days after myocardial infarction between
      older men and women, but when the early deaths were excluded, women showed an
      increased survival compared with men in the first year after the myocardial
      infarction.

PMID- 8855996
TI  - Antihypertensive medication use among recruits for the Trial of Nonpharmacologic
      Interventions in the Elderly (TONE).
AB  - OBJECTIVES: To examine the distribution and correlates of the classes of
      antihypertensive medications taken by persons aged 60 to 80. DESIGN: Cross
      sectional screening. SETTING: Four academic medical centers in the southern and
      eastern United States. PARTICIPANTS: Volunteers (N = 2601) entering a clinical
      trial testing the value of nonpharmacologic approaches to control blood pressure
      who were either taking one or two (single or combined) medications for the
      treatment of hypertension and expressed willingness to be withdrawn from these
      medications according to a standardized protocol. MEASUREMENTS: Medication use,
      blood pressure, and data from self-administered questionnaires collected during
      standardized clinic visits. RESULTS: Calcium channel blockers (23.9%) were the
      most frequent single agent antihypertensive medications used by cohort members,
      followed by diuretics (17.9%) and angiotension-converting enzyme (ACE) inhibitors
      (17.5%). The most common combination agents were composed of diuretics with
      either calcium channel blockers (5.4%), ACE inhibitors (4.0%), or beta-blockers
      (3.7%). Women were twice as likely to be taking diuretics, and less likely to be
      taking ACE inhibitors and beta-blockers, than men. Blacks were more likely to be
      taking diuretics and calcium channel blockers, and less likely to be taking beta
      blockers and ACE inhibitors, than others. These relationships could not be
      attributed to differences in geographical area, other demographic factors, age,
      or medical history. CONCLUSIONS: These usage patterns appear to mirror those in
      the population of the United States as a whole, which has trended toward greater
      usage of calcium channel blockers and ACE inhibitors with declining use of
      diuretics. The distribution of antihypertensive medications among older
      hypertensives is markedly different between women and men and between black
      Americans and others.

PMID- 8855997
TI  - Prognostic value of noninvasive risk stratification in younger and older patients
      referred for evaluation of suspected coronary artery disease.
AB  - OBJECTIVES: The purpose of this investigation is to explore the relationship of
      patient gender and age on coronary artery disease diagnostic evaluation and to
      assess the impact of noninvasive testing results on coronary revascularization
      rates and cardiac event-free survival. STUDY DESIGN: Retrospective observational
      cohort. PARTICIPANTS: From a series of 5322 consecutively tested patients from a
      Midwestern university tertiary medical center, a hospital cohort of 1345 patients
      with clinically suspected coronary artery disease was enrolled from 1988 through
      1989. MEASUREMENTS AND RESULTS: Cardiac risk factor and symptom profiles were
      worse in women, whereas rates of positive test results were similar in both
      sexes. Multivariable-adjusted risk for follow-up diagnostic testing was 1.8 and
      1.9 times greater, respectively, for men < or = and > 65 years of age than for
      women (P < .01). Younger women were 4.9 times (P = .001) more likely to
      experience a cardiac event than younger men, with no differences between younger
      and older women (relative risk = 1.1; P > .20). Overall cardiac event rates were
      2.3, 7.4, 16.7, and 20.2% for young men, young women, older women, and older men,
      respectively. Initial screening was delayed 2 to 7 times longer for older and
      younger women compared with men (P < .001); the greatest delays were observed for
      younger women. Diagnostic follow-up and subsequent cost of total care from
      initial evaluation through 2 years of follow-up were higher for men than for
      women (P < .0001), with older women having the lowest rate of subsequent
      diagnostic and interventional follow-up. In the highest risk patients, subsequent
      utilization rates were 40 and 20% higher for younger and older men than for
      similarly aged women. In particular, diabetics were less likely to undergo follow
      up diagnostic testing and revascularization (67% younger women). CONCLUSIONS: Age
      appears to significantly and differently influence decisions regarding
      noninvasive and invasive medical service utilization in men and women and may
      partially account for variable outcomes in this and previous gender-based
      comparisons.

PMID- 8855998
TI  - Can a physician recognize an older driver with increased crash risk potential?
AB  - OBJECTIVE: To identify factors in a medical examination that distinguish
      convicted older drivers with traffic violations from other drivers. DESIGN:
      Matched case-control study. SETTING: Two countries in Sweden. SUBJECTS: Thirty
      seven drivers older than age 65, whose driving licenses have been temporarily
      suspended, each matched to one control subject based on age, sex, type of driving
      license, year of first license, living area, educational level, and annual
      distance driven. MEASUREMENTS: Case and control subjects were compared with
      respect to medical history, medication use, blood tests, drawing and memory
      tests, Mini-Mental State Examination, medical status findings, visual acuity, and
      brain imaging procedures. MAIN RESULTS: The group of drivers with suspended
      driving licenses did not differ from matched controls with respect to visual
      acuity or presence of cardiovascular diseases. However, persons with suspended
      driving licenses were more likely than control subjects to have suspected or mild
      dementia (P < .010) and to perform less well on two easily administrated
      screening tests: copying a cube (P < .010) and 5-item recall (P < .010). Case
      subjects with crashes had significantly more cardiovascular diseases than case
      subjects with other moving violations (P < .050). These case subjects with
      crashes also had significantly more cognitive impairments than control subjects
      without crashes as shown by a higher clinical dementia rating score (CDR) (P <
      .001), lower score on the Mini-Mental State Examination (MMSE) (P < .050), and
      lower level of performance in the copying task (cube) (P < .050) and 5-item
      recall test (P < .010). They also had evidence of greater cognitive impairment
      than those case subjects with other moving violations. CONCLUSIONS: Visual acuity
      and common medical examination did not distinguish convicted older drivers with
      crashes or other moving violations from controls. There was evidence that even
      mild cognitive impairment contributed to the risk of losing a driving license
      because of crashes.

PMID- 8855999
TI  - Suicidal ideation among older primary care patients.
AB  - OBJECTIVE: To describe the prevalence and sociodemographic and clinical
      correlates of suicidal ideation among older primary care patients. DESIGN:
      Baseline screening for depressive symptoms, functional status, and suicidal
      ideation, with prospective assessment of mortality. SETTING: An academic primary
      care group practice at an ambulatory care clinic. PARTICIPANTS: 301 patients who
      screened positive for depression and a random sample of 101 patients who screened
      negative from among 3767 patients aged 60 and older who completed screening for
      depression during routine office visits. MEASUREMENTS: Centers for Epidemiologic
      Studies Depression (CES-D) scale, Hamilton Depression Rating (HAM-D) scale,
      Sickness Impact Profile (SIP), structured psychiatric interview, sociodemographic
      and clinical variables, and mortality. RESULTS: Among the 301 patients with CES-D
      scores > or = 16, 14 (4.6%) reported suicidal ideation and received urgent
      evaluation by mental health professionals. The estimated prevalence of suicidal
      ideation in this cohort of older primary care patients was 0.7 to 1.2%. All
      patients with suicidal ideation had evidence of a current affective disorder, and
      nearly all had moderate to severe functional impairment. However, even though all
      14 patients endorsed suicidal ideation, corresponding HAM-D scores ranged from 3
      to 40, and only four of 14 met diagnostic criteria for major depression. The most
      common suicide plan involved use of a hand gun. Depressed patients with suicidal
      ideation did not differ significantly from depressed non-suicidal patients on any
      of the following variables: age, gender, race, education, alcohol abuse,
      cognitive impairment, or mean CES-D, HAM-D, or SIP scores. None of the suicidal
      patients had died within 12 months of the screening date. CONCLUSION: The
      prevalence of suicidal ideation was about 1% among this cohort of older primary
      care patients, and the prevalence approaches 5% among those older adults who
      report significant symptoms of depression. However, asking patients directly
      about the presence of active suicidal ideation appears to be the only effective
      means of identifying those at risk.

PMID- 8856000
TI  - Patient factors associated with breast cancer screening among older women.
AB  - OBJECTIVES: To identify patient factors that influence physicians' decisions to
      recommend screening mammograms for older women. DESIGN: A cross-sectional survey
      including clinical case vignettes. PARTICIPANTS: Random sample of Massachusetts
      internists, obstetrician/gynecologists, family/general practice physicians, and
      geriatricians. OUTCOME MEASURE: Proportion of screening mammograms recommended
      for women in different versions of each case vignette. RESULTS: A total of 482
      (65%) of the eligible participants responded to a mailed survey of questions
      about breast cancer screening practices, attitudes toward ACS guidelines, and
      four clinical vignettes. Vignettes tested the impact of patient's age, cognitive
      function, nursing home residence, functional limitations, and comorbidity on the
      physician's decision to recommend a mammogram. Ninety-four percent of physicians
      reported often performing periodic clinical breast exams and mammograms for women
      aged 65 to 74. For women aged 75 to 84, 89% of physicians reported often
      performing periodic clinical breast exams, and 79% recommend mammograms. Only 48%
      strongly agreed with ACS guidelines for annual mammography for women over 65.
      Age, dementia, and nursing home residence were patient factors associated with
      decreased mammogram use, but limited mobility and chronic medical problems were
      not. Physicians were more likely to recommend a mammogram for a woman aged 65 to
      74 than for a woman 75 to 84. (P = .002) Physicians were more likely to recommend
      a mammogram for a woman without dementia than for a woman with mild dementia (P <
      .05) and for a woman living with her daughter than a for a woman living in a
      nursing home (P < .001). CONCLUSIONS: Age older than 75, mild dementia, and
      nursing home residence are factors that negatively influence physicians'
      decisions to recommend mammography. Presence of chronic medical problems and
      functional limitations do not. Physicians appear to be using implicit judgments
      about quality of life and age rather than life expectancy based on comorbidity to
      determine breast cancer screening practices.

PMID- 8856001
TI  - Physician responses to a hospital policy allowing them to not offer
      cardiopulmonary resuscitation.
AB  - OBJECTIVE: To determine whether physicians followed a hospital policy permitting
      them to not offer cardiopulmonary resuscitation (CPR) to patients considered
      unlikely to benefit from this therapy. DESIGN: Prospective series. SETTING: San
      Francisco General Hospital, a university-affiliated public hospital. PATIENTS:
      Attending physicians were interviewed about patients admitted over a period of 5
      consecutive months for whom do-not resuscitate (DNR) orders were written. Only
      the first patient for whom each physician wrote a DNR order was included. MAIN
      OUTCOME MEASURES: Responses of physicians to questions regarding their initiation
      of DNR orders for these patients. RESULTS: Sixty-nine physicians responded to
      questions about DNR orders written for 69 patients. Fifty-seven of these
      physicians said that they were aware of the hospital policy, and 49 of the 57
      physicians said that they generally agreed with it. Thirty-three physicians felt
      that CPR should be offered only to patients likely to benefit from it. In
      contrast, 36 physicians said that CPR should be offered to all patients,
      regardless of benefit. CPR was offered to 41 patients and 15 surrogates; 27 of
      these patients were considered to be unlikely to benefit from CPR. CONCLUSION:
      Despite a policy that allows them to do otherwise, physicians usually offered CPR
      to patients, regardless of benefit. Most physicians believed that CPR should be
      offered to all patients. These findings suggest that policies such as that of San
      Francisco General Hospital may not be compelling because physicians hold
      attitudes that are inconsistent with the policies.

PMID- 8856002
TI  - Impact of physical illness on quality of life and antidepressant response in
      geriatric major depression. Fluoxetine Collaborative Study Group.
AB  - OBJECTIVE: Because physical illness may influence quality of life, we assessed
      its impact on functional status and treatment outcome in older depressed patients
      who participated in a clinical trial, which showed a significantly higher
      remission rate for fluoxetine over placebo (31.6% vs 18.6%, P < .001). DESIGN:
      Six-week, randomized, double-blind, placebo-controlled trial of fluoxetine, 20 mg
      daily. SETTING: Multiple clinical sites, both university and private.
      PARTICIPANTS: Outpatients (N = 671) were > or = 60 years (mean +/- SD = 67.7 +/-
      5.7), met DSM-III-R criteria for unipolar major depression and had baseline
      scores > or = 16 on the Hamilton Depression Rating Scale. MEASUREMENTS: The 36
      item short-form health survey (SF-36) was used to measure baseline and
      posttreatment functional health and well-being. Physical illness was rated by
      number of current chronic or historical illnesses. Change from baseline to
      endpoint in the Hamilton Depression Rating Scale total score was used to measure
      depression outcome. MAIN RESULTS: Most patients reported physical illness: 83%
      had one or more chronic illness, and 89% had one or more historical illness.
      Greater numbers of baseline chronic illness indicated worse physical functioning,
      general health perceptions, and vitality and greater bodily pain and role
      limitation from physical problems. Historical physical illness was associated
      with worse physical functioning, vitality, general health perceptions, social
      functioning, and mental health. Although the number of chronic illnesses did not
      influence treatment response, historical physical illness was associated with
      greater fluoxetine response and lower placebo response. CONCLUSIONS: These
      findings suggest that both current and previous physical illness are associated
      with lower quality of life in geriatric depression and that depressed older
      patients with chronic physical illness respond to antidepressants as well as
      those without such illness. Recovery from previous physical illness should be
      explored as a potential predictor of antidepressant treatment outcome.

PMID- 8856003
TI  - Five-year performance trends for older exercisers: a hierarchical model of
      endurance, strength, and flexibility.
AB  - OBJECTIVE: To examine 5-year trends in measures of physical performance, and the
      impact of disease upon performance, in three domains: cardiovascular fitness,
      musculo-skeletal strength, and flexibility among older adults participating in a
      medically supervised exercise program. DESIGN: Longitudinal analyses of data
      obtained in an observational cohort study. SETTING: Department of Veterans
      Affairs Medical Center in Durham, North Carolina. PARTICIPANTS: Seventy-three
      community-dwelling veterans between 64 and 90 years of age. INTERVENTION:
      Voluntary participation in a medically supervised outpatient exercise program
      meeting 3 days per week for 90 minutes per session. MAIN OUTCOME MEASURES:
      Changes over time in cardiovascular fitness, musculoskeletal strength, and
      flexibility. RESULTS: Forty-nine percent of the original study participants
      remained in the program for a full 5 years. They had lower baseline rates of
      cardiorespiratory and musculoskeletal diseases than did the dropouts. Dropouts
      were significantly more impaired in baseline measures of cardiovascular fitness
      (P = .038) and strength (P = .007). Changes over time for cardiovascular fitness
      and strength were similar. Only linear (P < .05) and quadratic time (P < .001)
      were significant. Only linear time was significant for measures of flexibility (P
      < .05). Baseline cardiorespiratory disease, baseline musculoskeletal disease, and
      interaction terms were not significant. Overall, measures of physical performance
      demonstrated gradual improvement for 2 to 3 years, followed by a gradual decline
      in performance irrespective of baseline disease status. CONCLUSION: Older adults
      who exercise regularly, including those with multiple chronic diseases, can
      achieve significant gains in measures of physical performance, and these gains
      can be sustained for 2 to 3 years.

PMID- 8856004
TI  - No evidence for a higher resting metabolic rate in noninstitutionalized
      Alzheimer's disease patients.
AB  - OBJECTIVE: It has previously been suggested that Alzheimer's disease patients
      have higher resting energy requirements than healthy individuals, which may
      contribute to their unexplained weight loss. We examined whether resting
      metabolic rate, the largest component of daily energy expenditure, is elevated in
      Alzheimer's patients compared with healthy older controls. DESIGN: Cross
      sectional. SETTING: General Clinical Research Center and Baltimore VA Medical
      Center. PATIENTS: Twenty-five noninstitutionalized demented patients (74 +/- 8
      years; mean +/- SD) with a wide range of Mini-Mental Examination scores (1 to 20)
      and 73 healthy older individuals (69 +/- 7 years). MEASUREMENTS: Resting
      metabolic rate was measured by indirect calorimetry, fat-free mass and fat mass
      by dual energy X-ray absorptiometry, and daily energy intake by food diaries.
      RESULTS: No differences in fat-free mass and fat mass were noted between
      Alzheimer's disease patients and healthy older controls. Resting metabolic rate
      was similar in Alzheimer's disease patients (5446 +/- 962 kJ/day) and healthy
      older individuals (5647 +/- 887 kJ/day). These results persisted when resting
      metabolic rate was statistically adjusted for differences in body composition and
      age. CONCLUSION: These results provide no evidence for an elevation in resting
      energy requirements in noninstitutionalized demented patients.

PMID- 8856005
TI  - Management of complicated urinary tract infection in older patients.
AB  - Urinary tract infection (UTI) in older persons is a common medical problem that
      is seen in both the ambulatory and institutional settings. It affects older women
      and men with a gender prevalence ratio of 2:1, respectively. UTI in older persons
      can be a complex problem in terms of the approach to diagnosis, treatment, and
      prevention. In this report the discussion will begin with the unique aspects of
      UTI in older persons, particularly as they relate to UTI in the younger, general
      population. The remaining discussion will then focus on three complicated
      clinical circumstances and conditions of UTI in the geriatric population: non
      catheter recurrent UTI, asymptomatic bacteriuria, and catheter-related
      bacteriuria and UTI.

PMID- 8856006
TI  - Recent advances in the genetics of Alzheimer's disease and vascular dementia with
      an emphasis on gene-environment interactions.
AB  - OBJECTIVE: To review recent findings in the genetics of Alzheimer's disease (AD)
      and vascular dementia (VaD) with particular emphasis on gene-environment
      interactions. DESIGN: A survey and critique of recent literature on the genetic
      etiology of AD and VaD. CONCLUSIONS: Recent research has identified several genes
      associated with AD, including loci on chromosome 1, 14, 19, and 21. Two of these
      loci, encoding the beta-amyloid precursor protein and apolipoprotein E, have gene
      products that are well characterized and of evident significance in the
      pathogenesis of AD. The four genes together probably account for little more than
      50% of all cases of AD, but other undiscovered loci are likely. Interaction of
      genetic effects with environmental influences may affect both onset and
      expression of AD. By contrast, only a small minority of VaD cases can be
      attributed to a pure genetic etiology. The majority of VaD is caused by both
      genetic and environmental factors. Many of the environmental antecedents also
      have genetic determinants (e.g., smoking). Knowledge of the gene-environment
      interactions for both AD and VaD will facilitate identification of early
      preclinical symptoms of disease, a stage of the disease process during which
      treatment may be most beneficial.

PMID- 8856007
TI  - The promise and performance of HMOs in improving outcomes in older adults.
AB  - In summary, the promise of HMOs in caring for older adults far exceeds their
      performance to date. Until recently they had neither the motivation nor the
      knowledge to revamp their delivery systems to better needs of older, chronically
      ill patients. Market pressures and skyrocketing costs have provided the
      motivation. Physicians and researchers trained in epidemiology and health
      services research from programs such as that at UCLA are providing the knowledge.
      Based on the literature and experience described above, HMOs with the
      characteristics supportive of population-based care can put into place an
      approach to geriatric care likely to improve outcomes if they heed their patients
      and professionals rather than their accountants. These organizations will give
      highest priority to preserving function and will be guided by explicit clinical
      guidelines. Care will be rendered by organized primary care teams supported by
      systematic self-management approaches, standardized interventions for key risk
      factors, clinically useful computer systems, and available geriatric expertise.
      It will require a small revolution as old approaches, roles, and relationships
      will not go quietly. We are in the early phases of this revolution, and it's not
      too late to join us on the barricades.

PMID- 8856008
TI  - Old dog, new tricks?

PMID- 8856009
TI  - Gender and survival after myocardial infarction.

PMID- 8856010
TI  - The moral implications of medical uncertainty: tube feeding demented patients.

PMID- 8856011
TI  - Tube feeding the demented nursing home resident.
AB  - Despite the many complications and minimal benefits associated with long-term
      enteral nutrition in patients with advanced dementia, it is, nevertheless, a
      widespread practice in nursing homes throughout the United States. This paper
      presents a review of the literature on dementia, geriatric nutrition, and enteral
      feeding. There appears to be limited research to support the long-term benefits
      and safety of enteral nutrition in advanced dementia. Additionally, it is not yet
      clear that long-term enteral nutrition in advanced dementia results in an
      improved quality of life.

PMID- 8856012
TI  - Socioeconomic factors and hormone replacement therapy in older British women.

PMID- 8856013
TI  - The P300 and vascular dementia: not quite ready for prime time.

PMID- 8856014
TI  - Prevalence and diagnosis of cobalamin deficiency in older people.

PMID- 8856015
TI  - Are U.S. lower normal B12 limits too low?

PMID- 8856016
TI  - Rational utilization of psychotropic agents.

PMID- 8856017
TI  - Ethnogeriatrics and functional status.

PMID- 8856018
TI  - Dementia care.

PMID- 8856019
TI  - 5th International Symposium on Resistance Arteries. Cambridge, United Kingdom,
      September 25-29, 1996. Abstracts.

PMID- 8856020
TI  - A new sequence variant of Coleus blumei viroid 3 from the Coleus blumei cultivar
      'Fairway Ruby'.
AB  - A viroid was isolated from symptomless Coleus blumei cultivar (cv) 'Fairway Ruby'
      plants using the bidirectional PAGE method for analysis of small circular RNA
      molecules. The viroid was transmitted to viroid-free plants of Coleus blumei cv.
      'Scarlet Dragonfly' by mechanical inoculation. Cloning and sequencing revealed
      that the viroid from the Coleus cv. 'Fairway Ruby' is closely related to the
      Coleus blumei viroid 3-Bv (CbVd 3-Bv) isolated from the Coleus cv. 'Bienvenue'.
      Therefore, the new viroid sequence variant has been named Coleus blumei viroid 3
      FR (CbVd 3-FR). Coleus blumei viroid 3-FR consists of 364 nucleotides, 202 G + C,
      162 A + U with a GC content of 55.5%. The most stable rod-like secondary
      structure of this viroid has 82 G:C, 50 A:U and 10 G:U base pairs with a minimum
      free energy of -670.5 kJ/mol (-160.4 kcal/mol). Due to mutations that increase
      the stability of the rod-like secondary structure, CbVd 3-FR has a lower minimum
      free energy than CbVd 3-Bv (-598.2 kJ/mol; -143.1 kcal/mol). A base-exchange in
      the upper strand of the central domain of CbVd 3-FR may stabilize the basal helix
      of hairpin I.

PMID- 8856021
TI  - A viroid from Solanum pseudocapsicum closely related to the tomato apical stunt
      viroid.
AB  - A viroid was isolated from symptomless Solanum pseudocapsicum cultivar (cv) 'New
      Patterson' plants using the bidirectional PAGE method for analysis of small
      circular RNA molecules. The viroid was transmitted to tomato by mechanical
      inoculation. Infected tomato plants developed symptoms similar to those caused by
      potato spindle tuber viroid (PSTVd). Cloning and sequencing revealed that the
      viroid from Solanum pseudocapsicum is closely related to the tomato apical stunt
      viroid (TASVd). Therefore, the new viroid sequence variant has been named TASVd
      S. The circular RNA of TASVd-S consists of 360 nucleotides which can potentially
      form a rod-like structure with a high degree of base-pairing like all the other
      known viroids. The nucleotide composition is 99 G, 72 A, 101 C and 88 U,
      corresponding to 200 G + C, 160 A + U with a GC content of 55.6%. In total 71% of
      the residues are base-paired and the basepaired residues consist of 73 G:C (57%),
      43 A:U (34%) and 11 G:U (9%) base pairs. The most stable rod-like secondary
      structure of this viroid has 80 G:C, 39 A:U and 11 G:U base pairs with a minimum
      free energy of -147.5 kcal/mol (-616.6 kJ/mol). The sequence similarity of the
      left terminal (T1) domain of TASVd-S and the T1 domain of tomato planta macho
      viroid (TPMVd) is higher than the sequence similarity of these domains of TASVd-S
      and TASV-d.

PMID- 8856022
TI  - Polygenic control of antibody production and correlation with vaccine induced
      resistance to rabies virus in high and low antibody responder mice.
AB  - The amplification of "high" (H) and "low" (L) multispecific antibody responses
      achieved respectively by H and L lines of selection GP represents a valuable tool
      in the genetic study of host-infection interactions. These lines were obtained by
      bidirectional selective breeding for high (HGP) or low (LGP) antibody production
      to natural complex antigens. HGP and LGP parental lines and reciprocal F1
      hybrids, as well as their F2 segregants and backcrosses were submitted to
      immunization and challenge with rabies virus CVS strain. Acquired resistance was
      1000-fold higher in HGP than LGP mice, with a dominance effect to low antibody
      production observed in F1 hybrids. An association between high antibody response
      and acquired resistance (P < 0.001) in F2 segregant mice was noticed. The genetic
      study was performed in these several populations, with a single dose of 104.5
      fold LD50 CVS. We could demonstrate 3 independent loci regulating the anti-rabies
      antibody production, that are distinct, at least in part, from the 10 genes
      controlling the antigen selection response (sheep erythrocytes) of selection GP.

PMID- 8856023
TI  - Antigenic analysis of type O foot-and-mouth disease virus in the persistently
      infected bovine.
AB  - The antigenic profiles of serotype O strains of FMDV collected from the
      oropharynx of persistently infected cattle were defined with a panel of
      monoclonal antibodies (mAb's) in an indirect antigen-trapping ELISA. The mAb
      profiling showed no significant loss of reactivity in two neutralising antigenic
      sites of persistent FMDV isolates collected over a period of eight months. Early
      and late serum taken from a carrier animal showed similar neutralising activity
      against early and late carrier isolates. The antigenic stability of serotype O
      strains of FMDV collected during the carrier state suggests that antigenic
      variation facilitated by pressure from the host humoral immune response is not
      critical to the establishment or maintenance of a persistent infection with FMDV.

PMID- 8856024
TI  - Oral immunization of rabbits with VP60 particles confers protection against
      rabbit hemorrhagic disease.
AB  - Rabbit hemorrhagic disease virus (RHDV) causes more than 90% mortality in adult
      rabbits. In this study, the cDNA of the VP60 coding sequence of RHDV was cloned
      under the control of the polyhedrin and p10 promoters of baculovirus to be
      expressed in insect cells. The expression of RHDV VP60 under the control of the
      p10 promoter was 5-10 times higher than using the polyhedrin promoter. The p10
      derived VP60 was able to assemble into virus-like particles (VLPs). RHDV VLPs
      were successfully used to protect rabbits against the disease even at doses as
      low as 0.5 micrograms when injected intramuscularly or subcutaneously. The
      ability to elicit an immune response was independent of the adjuvant or the route
      of immunization. Remarkably, oral administration of RHDV VLPs efficiently induced
      protecting antibodies to RHD at doses as low as 3 micrograms. The use of binary
      ethylenimine for the stabilization of the VLPs was decisive for eliciting a good
      oral immunity. This report demonstrates the potential use of these procapsids in
      obtaining RHD oral vaccines and opens the door to the use of these capsids for
      the prevention of the disease in wild animals. Therefore, a new, and potentially
      important application of recombinant VLPs in the induction of protective immunity
      by the oral route is foreseen.

PMID- 8856025
TI  - Genome analysis of the 3'-terminal part of the little cherry disease associated
      dsRNA reveals a monopartite clostero-like virus.
AB  - The high molecular weight dsRNA associated with little cherry disease (LCD) was
      extracted from infected plant tissue and cloned as cDNA. The sequence of the 3'
      8337 nucleotides was determined. Computer assisted translation of the sequence
      portion identified six open reading frames potentially encoding proteins (from 5'
      to 3') with molecular masses of 70 kDa, 61 kDa, 46 kDa, 76 kDa, 21 kDa and 27 kDa
      respectively. A 3'-terminal non-translated region of 210 nucleotides was present.
      The 70 kDa protein represents a homolog of the cellular HSP70 heat shock
      proteins, and the 61 kDa protein showed homology to the similarly encoded
      products of beet yellows (BYV), citrus tristeza (CTV) and lettuce infectious
      yellows (LIYV) closteroviruses. The putative coat protein (CP) was found to be of
      46 kDa and its diverged copy of 76 kDa. The potential coding capacity of these
      notably large closterovirus proteins was confirmed by their expression in vitro
      and immunoblotting. No proteins with significant similarity to the two C-terminal
      proteins were identified, but they are related in molecular mass and location to
      BYV. The gene arrangement as well as the alignments of the closteroviruses CPs
      and their diverged copies suggest that the mealybug transmissible virus
      associated with LCD takes an intermediate evolutionary position between the aphid
      and whitefly transmissible closteroviruses.

PMID- 8856026
TI  - Evidence that neomycin inhibits human cytomegalovirus infection of fibroblasts.
AB  - The effect of phosphoinositide-binding aminoglycosides, such as neomycin,
      gentamicin and streptomycin, on human cytomegalovirus (HCMV) infection of human
      fibroblasts MRC-5 was studied. The inhibition of HCMV infection was obtained with
      all of these molecules but neomycin was more effective than the others. We showed
      that the inoculation of the cells with cell-free viral suspension in presence of
      neomycin concentrations above 5 mM at 37 degrees C, inhibited more than 98% the
      HCMV infection. However, the preincubation of the fibroblasts with neomycin at 4
      degrees C, before the removal of the drug and the inoculation of the cells,
      induced only a 30% decrease in the number of infected cells. Addition of neomycin
      after the HCMV-binding at 4 degrees C or the infection of the cells was less
      efficient to inhibit HCMV infection than the standard incubation of neomycin
      during inoculation of the fibroblasts. Indeed, 1 hour after the inoculation of
      the cells at 37 degrees C, neomycin still inhibited HCMV infection, but 4 hours
      after the inoculation, this drug had no effect on HCMV infection. Our findings
      demonstrated that neomycin must be present at the time of infection in order to
      exert a full inhibiting effect. The effect of neomycin on the HCMV infection was
      almost immediate upon the addition of the drug (binding and/or internalization)
      and after the virus internalization (inhibition of immediate-early events). We
      suggest that neomycin and other aminoglycoside antibiotics may interact with HCMV
      glycoproteins for binding to similar structural features of cell surface heparan
      sulfate proteoglycans and may inhibit HCMV infection in fibroblasts by disrupting
      phosphoinositide-mediated events in the cells.

PMID- 8856027
TI  - Glycoprotein E2 of bovine viral diarrhea virus expressed in insect cells provides
      calves limited protection from systemic infection and disease.
AB  - Calves were vaccinated with a C-terminally truncated baculovirus expression
      product of E2 from the Singer strain of bovine viral diarrhea virus. The
      expressed E2 was glycosylated and retained antigenic authenticity. After
      induction of viral neutralizing antibody, the calves were challenge exposed with
      either the homologous Singer strain of virus or with the heterologous 890 strain
      of virus. Vaccine-induced antibody titer of > or = 2 protected calves from
      clinical signs of disease induced by homologous viral challenge exposure. An
      antibody titer of > or = 512 reduced replication of homologous challenge virus to
      a level which did not induce an appreciable increase in serologic titer of viral
      neutralizing antibody. Vaccine-induced antibody titer of < or = 4096 did not
      protect calves from systemic spread of virus or from disease after challenge
      exposure with heterologous bovine viral diarrhea virus.

PMID- 8856028
TI  - Ultrastructural studies on the replication and morphogenesis of Nairobi sheep
      disease virus, a Nairovirus.
AB  - The Nairovirus Nairobi sheep disease virus (NSDV) affects sheep and goats causing
      severe hemorrhagic gastroenteritis and high mortality. Replication and
      morphogenesis of NSDV was determined by electron microscopic examination of ultra
      thin sections of 143B and BHK-21 cells at varying times after infection. By 4 h
      post-infection (p.i.) of 143B cells, virions budding from the luminal side of the
      bilayer membrane of smooth membrane vesicles were observed. Morphologically
      mature virus particles were electron-dense, spherical and of uniform size (100 nm
      diameter) and accumulated in smooth membrane vesicles associated with the Golgi
      complex. In BHK-21 clone 13 cells, mature virus particles in smooth membrane
      vesicles were present by 8 h p.i. The morphogenesis of NSDV was restricted to the
      smooth membrane vesicles of Golgi complex, and budding of virus from other sites
      was not detected. Extracellular virus particles were observed by 10 h p.i.,
      before expression of cytopathic effects. The cytopathic effects were observed at
      24 h p.i. in 143B cells and at 36 h p.i. in BHK-21 cells. The morphology and
      morphogenesis of NSDV in BHK-21 cells and in 143B cells resembles that of other
      members of the family Bunyaviridae.

PMID- 8856029
TI  - Epitope mapping of capsid proteins VP2 and VP3 of infectious bursal disease
      virus.
AB  - Twenty hybridoma cell lines producing monoclonal antibodies (MAbs) against
      serotype 1 infectious bursal disease virus (IBDV) of GBF-1 and the attenuated GBF
      1E strains were produced. The MAbs recognized major structural proteins VP2 and
      VP3. MAb recognition sites were mapped using recombinant Escherichia coli clones
      which expressed N-terminal and (or) C-terminal truncated virus antigens, and
      competitive-binding assays. At least 3 conformation-dependent serotype 1 specific
      virus neutralizing antigenic sites and a linear antigenic site were defined on
      VP2 and VP3, respectively. Two of the conformational virus neutralizing antigenic
      sites were localized in the central area of VP2 consisting of 156 amino acid
      residues, and the linear epitope was localized in C-terminal 105 amino acid
      residues of VP3. Another conformational virus neutralizing antigenic site
      recognized with the virus neutralizing MAb GK-5 was not defined because GK-5 did
      not react with virus antigen expressed in recombinant E. coli. The conformational
      antigenic site was supposed to be composed of tertiary or quaternary protein
      structure, which may not be constructed in recombinant E. coli.

PMID- 8856030
TI  - A molecular taxonomy for cricket paralysis virus including two new isolates from
      Australian populations of Drosophila (Diptera: Drosophilidae).
AB  - Two new isolates of cricket paralysis virus, TAR and SIM, are described that were
      originally isolated from laboratory colonies of Drosophila melanogaster and
      Drosophila simulans respectively. Using a combination of biological, serological
      and molecular characters it was possible to distinguish the SIM isolate from all
      other isolates and it is thus described as a new strain; CrPVSIM. The TAR isolate
      however, was indistinguishable from the CrPV reference isolate
      CrPVVIC/GM/D2(2)/Gm/D2(2) (Teleogryllus commodus, Victoria, Australia, 1968). The
      molecular characters used in the present study were obtained by combining PCR and
      restriction endonuclease digestion of the amplified fragments. This work
      demonstrates that such molecular characters, when used in combination with
      others, provide a powerful set of taxonomic characters for classifying CrPV
      isolates and strains and assessing their genetic relatedness.

PMID- 8856031
TI  - Investigation of the transfection capability of cloned tandemly-repeated chicken
      anaemia virus DNA fragments.
AB  - Chicken anaemia virus (CAV) is an icosahedral virus, 25 nm in diameter, which, on
      the basis of its circular single-stranded DNA genome, has recently been
      classified in the family, Circoviridae. We have investigated whether infectious,
      monomeric CAV DNA from recombinant plasmids containing tandemly-repeated CAV
      replicative form (RF) DNAs, following transfection, was generated by homologous
      recombination or a replicational release mechanism involving rolling circle
      replication (RCR) of DNA. Experiments designed to locate the virus strand origin
      of RCR and/or sites of recombination were performed by sequence analyses of
      hybrid viruses generated after transfection with cloned tandemly-repeated RFs
      specified by the sequence-distinct Cux-1 and 26P4 isolates. Positive transfection
      results obtained from 2 recombinant plasmid constructs were shown to have
      resulted from homologous recombination occurring at different sites within the RF
      sequence. Three of 5 hybrid viruses analysed were "circularised" within the same
      105 bp sequence, that contains four 19bp repeats and with which promoter/enhancer
      activity has been associated. This region may represent a novel origin or
      recombination hot-spot within the CAV genome. A distinctive cruciform-loop
      structure within the non-coding region was shown to contain an S1 nuclease
      sensitive site, detected in CAV RF and in recombinant plasmids containing RF
      inserts.

PMID- 8856032
TI  - Construction and analysis of infectious transcripts from a resistance-breaking
      strain of tobacco vein mottling potyvirus.
AB  - The Burley tobacco (Nicotiana tabacum) cultivar TN 86 is "resistant" to most
      strains of tobacco vein mottling potyvirus (TVMV), the virus being restricted to
      epidermal cells of inoculated leaves. One strain, designated TVMV-S, overcomes
      this resistance and infects cv TN 86 systemically. To begin our investigation of
      the molecular basis for the resistance-breaking phenomenon, we have completed the
      cloning and sequencing of the TVMV-S RNA genome. The complete cDNA clone, under
      the control of a T7 RNA polymerase promoter, was used to produce infectious
      transcripts which were tested for their ability to reproduce the characteristics
      of TVMV-S RNA on three types of tobacco (N. tabacum cv TN 86, N. tabacum cv KY
      14, and N. benthamiana). Timing of symptom appearance, symptom type, and titer of
      virus were identical to those of plants inoculated with TVMV-S RNA. As a step
      toward mapping the responsible genetic region(s) that contribute(s) to resistance
      breaking by TVMV-S, the nucleotide and deduced amino acid sequences were compared
      to those of wild-type TVMV, a strain that does not overcome cv TN 86 resistance.
      Variant TVMV-S transcripts containing changes within the VPg cistron exhibited an
      altered pattern of infectivity on cv TN 86.

PMID- 8856033
TI  - Previous H1N1 influenza A viruses circulating in the Mongolian population.
AB  - Four influenza A viruses of the subtype H1N1, isolated from Mongolian patients in
      Ulaanbaatar between 1985 and 1991, were analysed by sequencing of various RNA
      segments. The isolate from 1985 was found to be highly related in all genes
      sequenced to strains isolated from camels in the same region and at about the
      same time. These camel isolates were presumably derived from a UV-light
      inactivated reassortant vaccine (PR8 x USSR/77) prepared in Leningrad in 1978 and
      used in the Mongolian population at that time [19]. The human isolate from 1988
      was also found to be a derivative of a reassortant between PR8 and USSR/77; in
      contrast to the 1985 isolate, however, it contained an HA closely related to PR8.
      One of the Mongolian isolates from 1991 (111/91) was in all genes sequenced
      closely related to PR8, while the other isolate from 1991 (162/91) was closely
      related to H1N1 strains isolated around 1986 in other parts of the world. About
      12% of 235 convalescent sera collected in various parts of Mongolia contained
      antibodies against PR8, while none of German control sera contained such
      antibodies. The mutational and evolutionary rates of the Mongolian strains seem
      to be significantly lower when compared to the rates of human influenza A strains
      isolated in other parts of the world. This might indicate that these rates depend
      to a certain extent on the population density. Thus, viruses from remote areas
      might keep the potential to reappear in the human population after several years
      to cause a pandemic as it had happened in 1977.

PMID- 8856034
TI  - Inhibitory effect of pulmonary surfactant on Sendai virus infection in rat lungs.
AB  - Intranasal infection of rats with active (infectious) Sendai virus enhances
      secretion of tryptase Clara, a Sendai virus-activating protease, into the
      bronchial lumen by Clara cells of the bronchial epitheliums, and inversely
      suppresses secretion of pulmonary surfactant, an inhibitor of the protease, into
      the lumen [Kido H et al. (1993) FEBS Lett 322: 115-119]. A trypsin-resistant
      mutant, TR-2, showed similar effects, although its replication was restricted to
      a single cycle in the lungs. In contrast, neither nonactive (noninfectious) wild
      type virus possessing receptor-binding activity and lacking envelope fusion
      activity nor UV-inactivated virus retaining receptor binding and envelope fusion
      activities altered the mode of secretions. These results indicate that viral
      replication is required for producing a condition in the bronchial lumen for
      proteolytic activation of progeny virus, thereby infection is extended to a fatal
      pneumonia. On the other hand, intranasal administration of infected rats with
      pulmonary surfactant suppressed activation of progeny virus and pathological
      changes in the lungs, suggesting a therapeutic use of pulmonary surfactant for
      influenza pneumonia.

PMID- 8856035
TI  - Effect of protectants in L-drying on the conformation and infectivity of rice
      dwarf phytoreovirus.
AB  - Purified rice dwarf phytoreovirus preparations, after rehydration following
      drying without freezing (L-drying) and sucrose density gradient centrifugation,
      sedimented to the same position as untreated controls. Upon storage at 65 degrees
      C, virion conformation in L-dried preparations supplemented with 1% sucrose was
      maintained better than without additives. Moreover, during storage for 6 years at
      -70 degrees C, infectivity of L-dried preparations from crude extracts of
      infected rice plants containing 5% sucrose was higher than controls based on the
      number of count of infected foci on cell monolayers and transmission to rice
      seedlings by leafhopper of the vector Nephotettix cincticeps, which had been
      injected with such extracts.

PMID- 8856036
TI  - Thogoto and Dhori virus replication is blocked by inhibitors of cellular
      polymerase II activity but does not cause shutoff of host cell protein synthesis.
AB  - Tick-transmitted Thogoto and Dhori viruses share structural and genetic
      properties with the influenza viruses. Here, we compare different steps of their
      replication cycle in mammalian cells in comparison with influenza A virus. Viral
      antigens of both viruses accumulated in the nuclei of infected cells, suggesting
      a nuclear phase of viral replication. Furthermore, as observed with influenza
      viruses, transcription of Thogoto and Dhori viruses was inhibited by alpha
      amanitin and actinomycin D, suggesting a dependence of viral transcription on
      cellular RNA polymerase II activity. In contrast to influenza viruses, Thogoto
      and Dhori virus infection did not lead to down-regulation of cellular protein
      synthesis indicating marked differences regarding the fate of infected cells.

PMID- 8856037
TI  - Oxygenation of (3Z)-alkenal to (2E)-4-hydroxy-2-alkenal in soybean seed (Glycine
      max L.).
AB  - (3Z)-Alkenals, such as (3Z)-hexenal and (3Z)-nonenal, are produced from
      polyunsaturated fatty acids via lipoxygenase and hydroperoxide lyase catalysis,
      but in soybeans (Glycine max L.) (3Z)-alkenals have a fleeting existence. In this
      study it was shown that soybean seeds possess two pathways that metabolize (3Z)
      alkenals. One is a soluble (3Z):(2E)-enal isomerase that transformed (3Z)-hexenal
      and (3Z)-nonenal into the corresponding (2E)-alkenals. The other was a membrane
      bound system that converted (3Z)-hexenal and (3Z)-nonenal into (2E)-4-hydroxy-2
      hexenal and (2E)-4-hydroxy-2-nonenal, respectively. The latter conversion was
      shown to absorb O2 with a pH optimum of 9.5. Little effect observed with
      lipoxygenase inhibitors suggested that oxidation was not catalyzed by
      lipoxygenase. Instead, a specific (3Z)-alkenal oxygenase was implicated in
      forming intermediate alkenal hydroperoxides. Hydroperoxide-dependent peroxygenase
      (epoxygenase) is known to reduce hydroperoxides to their corresponding hydroxides
      and is also known to be inhibited by hydrogen peroxide preincubation.
      Consequently, intermediate 4-hydroperoxy-2-alkenals could be observed after
      inhibiting hydroperoxide-dependent peroxygenase by preincubation with hydrogen
      peroxide. Because 4-hydroxy-2-alkenals are potent toxins, these compounds may be
      produced as nonvolatile plant defensive substances.

PMID- 8856038
TI  - Human non-pancreatic (group II) secreted phospholipase A2 expressed from a
      synthetic gene in Escherichia coli: characterisation of N-terminal mutants.
AB  - A gene coding for human non-pancreatic (group II) secreted phospholipase A2
      (hnpsPLA2) has been constructed by the single-step ligation of twelve synthetic
      oligonucleotides. The gene has been cloned into a modification of the bacterial
      expression vector pET 11 which allows protein over-expression as inclusion bodies
      and enables about 3 mg/litre of pure refolded fully active enzyme to be obtained.
      The protein was expressed as a 1-Ala mutant (N1A) to allow removal of the
      initiator methionine by the Escherichia coli amino-peptidase. This mutant had
      very similar properties to the wild-type enzyme. A double mutant, N1A, V3W was
      also constructed and expressed in high yield. This tryptophan-containing mutant
      showed similar properties to the wild-type and N1A mutant but had about 40% of
      the activity under the assay conditions used. This tryptophan was used as a
      reporter group for interfacial binding and its properties were compared to those
      of the corresponding tryptophan in PLA2 from procine pancreas. Expression of the
      wild-type gene sequence for hnpsPLA2 in E. coli gave the expected mutant protein
      still with the initiator methionine and with much reduced activity. Interfacial
      binding of all hnpsPLA2 mutants to anionic phospholipids was very similar when
      assessed by fluorescence methods. Comparisons of these mutants with the
      pancreatic enzyme revealed significant differences in terms of the effect of
      calcium on interfacial binding. The ability to express reasonably large amounts
      of the N1A mutant in E. coli will provide a basis for future site directed
      mutagenesis studies of this important human enzyme.

PMID- 8856039
TI  - Plasma phospholipid mass transfer rate: relationship to plasma phospholipid and
      cholesteryl ester transfer activities and lipid parameters.
AB  - Human plasma phospholipid transfer protein (PLTP) has been shown to facilitate
      the transfer of phospholipid from liposomes or isolated very low and low density
      lipoproteins to high density lipoproteins. Its activity in plasma and its
      physiological function are presently unknown. To elucidate the role of PLTP in
      lipoprotein metabolism and to delineate factors that may affect the rate of
      phospholipid transfer between lipoproteins, we determined the plasma phospholipid
      mass transfer rate (PLTR) in 16 healthy adult volunteers and assessed its
      relationship to plasma lipid levels, and to phospholipid transfer activity (PLTA)
      and cholesteryl ester transfer activity (CETA) measured by radioassays. The
      plasma PLTR in these subjects was 27.2 +/- 11.8 nmol/ml per h at 37 degrees C
      (mean +/- S.D.), and their PLTA and CETA were 13.0 +/- 1.7 mumol/ml per h and
      72.8 +/- 15.7 nmol/ml per h, respectively. Plasma PLTR was correlated directly
      with total, non-HDL, and HDL triglyceride (rs = 0.76, P < 0.001), total and non
      HDL phospholipid (rs > 0.53, P < 0.05), and inversely with HDL free cholesterol
      (rs = -0.54, P < 0.05), but not with plasma PLTA and CETA. When 85% to 96% of the
      PLTA in plasma was removed by polyclonal antibodies against recombinant human
      PLTP, phospholipid mass transfer from VLDL and LDL to HDL was reduced by 50% to
      72%, but 80% to 100% of CETA could still be detected. These studies demonstrate
      that PLTP plays a major role in facilitating the transfer of phospholipid between
      lipoproteins, and suggest that triglyceride is a significant modulator of
      intravascular phospholipid transport. Furthermore, most of the PLTP and CETP in
      human plasma is associated with different particles. Plasma PLTA and CETA were
      also measured in mouse, rat, hamster, guinea pig, rabbit, dog, pig, and monkey.
      Compared to human, PLTA in rat and mouse was significantly higher and in rabbit
      and guinea pig was significantly lower while the remaining animal species had
      PLTA similar to humans. No correlation between PLTA and CETA was observed among
      animal species.

PMID- 8856040
TI  - Inhibition of copper- and peroxyl radical-induced LDL lipid oxidation by ebselen:
      antioxidant actions in addition to hydroperoxide-reducing activity.
AB  - The effects of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) on human LDL
      lipid oxidation induced by different fluxes of aqueous peroxyl radicals and
      cupric ion (at a Cu2+:LDL ratio of 17:1) were investigated. Addition of ebselen
      to LDL oxidised with Cu2+ prolonged the duration of the lag-phase typical for
      this oxidising condition, with the increase being proportional to the square of
      the ebselen concentration. Ebselen also prevented the formation of lipid
      hydroperoxides and inhibited the consumption of endogenous antioxidants during
      the early period of Cu(2+)-induced oxidation, during which time the drug was
      converted stoichiometrically into ebselen oxide (2-phenyl-1,2-benzisoselenazol
      3(2H)-one-Se-oxide). Ebselen oxide itself was antioxidant inactive. Ebselen also
      inhibited formation of lipid-hydroperoxides and spared alpha-tocopherol during
      the initial stages of LDL oxidation mediated by low-flux of aqueous peroxyl
      radicals, where a lag-phase was not observed. When a higher flux of aqueous
      peroxyl radicals was used, ebselen increased the observed inhibited phase of
      peroxidation in a dose-dependent manner, though less pronounced than its
      prolongating effect on the lag-phase of Cu(2+)-induced LDL lipid oxidation.
      Ebselen was also able to directly interact with Cu1+, alkyl peroxyl radicals and
      alpha-tocopheroxyl radicals, demonstrating that the drug has a number of
      potential antioxidant activities in addition to its well-known hydroperoxide
      reducing activity. We conclude that the antioxidant activities of ebselen are
      complex and that their relative importance likely vary depending on the
      experimental system used.

PMID- 8856041
TI  - Guinea pig intestinal phospholipase B: protein expression during enterocyte
      maturation and effects of N-oligosaccharide removal on enzymatic activities and
      protein stability.
AB  - Guinea pig phospholipase B (PLB) is an intestinal brush-border hydrolase
      displaying a broad substrate specificity towards various dietary lipids. PLB was
      detected by immunoblotting as a single 140-kDa polypeptide in all cell
      populations isolated from guinea pig intestinal mucosa, but increased in parallel
      to its activity from undifferentiated to mature cells, the specific activity of
      the enzyme remaining constant. Moreover, N-glycosylation, which contributed to
      23% of the apparent molecular mass, was identical along the cell differentiation
      axis. In all cell fractions, N-linked sugar chains were of the complex type,
      since they were removed by N-glycosidase F, whereas PLB remained insensitive to
      endoglycosidase H. Moreover, lack of O-glycosylation was demonstrated by the
      insensitivity of PLB to O-glycosidase and by its failure to interact with Helix
      pomatia lectin after prior treatment with neuraminidase or alpha-fucosidase.
      Enzymatic removal of sugar chains reduced phospholipase A2, lysophospholipase and
      diacylglycerol lipase activities by 27-35%, kinetic analysis indicating a
      decrease in apparent Vmax values for the three enzymatic activities, whereas the
      Km remained unchanged. Finally, the carbohydrate-depleted form of PLB did not
      display gross changes in thermal stability, in contrast to PLB from
      microorganisms previously investigated. Our data indicate that the high level of
      PLB N-glycosylation is poorly related to its biological function. Whether
      carbohydrate chains are involved in proper targeting of the enzyme to the brush
      border membrane remains to be established.

PMID- 8856042
TI  - Biosynthesis of arachiodonic acid metabolites in Limulus polyphemus amebocytes:
      analysis by liquid chromatography-electrospray ionization mass spectrometry.
AB  - Eicosanoid metabolites were generated by isolated granular amebocytes of the
      primitive arthropod, Limulus polyphemus, when stimulated by the calcium ionophore
      A23187 and/or exogenous arachidonic acid. The metabolites were isolated,
      identified, and the major metabolite was quantified using reverse-phase high
      pressure liquid chromatography (RP-HPLC) coupled to electrospray ionization mass
      spectrometry (ESI-MS). Qualitative examination revealed putative metabolites and
      the major product, 8-hydroxyeicosatetraenoic acid (8-HETE), which was quantified
      using standard curves generated from extracted ion profiles of the molecular ion.
      Electrospray ionization of the HETEs in negative ion mode produces a base peak
      for all isomers which corresponded to the molecular ion [(M-H)-: m/z 319]. The
      molecular ion was accompanied by the neutral loss of water and carbon dioxide [(M
      H -H2O)-: m/z 301; (M-H -H2O -CO2)-: m/z 257], as well as daughter ions which
      were dependent upon the position of hydroxy substitution. Standard curves were
      generated in full scan mode for standards ranging from 6.25 to 100 ng, whereas
      selected ion recording was used for the lower levels of 0.8 to 6.25 ng.

PMID- 8856043
TI  - Remodeling of HDL containing apoA-I but not apoA-II (LpA-I) by lipoprotein
      deficient plasma and hepatic lipase: its effect on the structure and cellular
      cholesterol-reducing capacity of LpA-I.
AB  - We investigated the effects of lipoprotein-deficient plasma (LDP) and hepatic
      lipase (HL) on the structure and cellular cholesterol-reducing capacity of
      subclasses of LpA-I (HDL containing apoA-I but not apoA-II). LpA-I is composed of
      large (11.1 nm; L-LpA-I), medium (8.8 nm: M-LpA-I) and small (7.7 nm: S-LpA-I)
      particles. L-LpA-I and M- and S-LpA-I combined (MS-LpA-I) were incubated with
      lipoprotein-deficient plasma and HL in the presence of very low density
      lipoprotein (VLDL). After incubation of L-LpA-I, the proportions of cholesteryl
      esters and phospholipids decreased and as a result, the proportion of protein
      increased. The remodeled L-LpA-I particles were generally smaller (spherical: 7.8
      8.8 nm) in diameter. A small number of disc-shaped particles were also found in
      electron photomicrographs. These changes coincided with a slower electrophoretic
      mobility of remodeled L-LpA-I. In the case of MS-LpA-I, only the proportion of
      free cholesterol increased after incubation, and MS-LpA-I particles did not
      change in size. The cholesterol-reducing capacities of remodeled L-LpA-I and MS
      LpA-I from macrophage foam cell were slightly higher and lower than their
      respective original counterparts, although neither of these differences was
      statistically significant. These results suggest that LDP and HL mainly
      contribute to the remodeling of L-LpA-I particles, and may not affect the
      cellular cholesterol-reducing capacity of these particles.

PMID- 8856044
TI  - Lipid differentiation in MP26 junction enriched membranes of bovine lens fiber
      cells.
AB  - The present study was undertaken to address the question whether lipid
      differentiation occurs in junctional domains which could imply a functional
      requirement for specific lipids in junctional structures. Junction enriched
      membranes were isolated from bovine lens fiber cells using Tris and urea
      treatment, and the presence of junctional structures was ascertained by electron
      microscopy. Enrichment in major intrinsic protein (MIP, MP26) was monitored by
      SDS polyacrylamide gel electrophoresis. Junctional lipids were extracted by a
      modified Folch procedure, to quantitatively recover cholesterol, and lipid
      classes were analyzed. While 99.5% of total lens protein was solubilized in the
      course of junction isolation, 43.9% of cell phospholipids (PL) and 64.1% of cell
      cholesterol (Chol) were conserved. Cholesterol was by far the predominant lipid
      in the junction enriched lens fiber cell membranes (833 nmol/mg protein) and was
      more abundant than all phospholipids combined (682 nmol/mg protein). In isolating
      the junctional membranes, cholesterol levels increased 144-fold, and average
      phospholipid levels increased 99-fold, which resulted in an increase in Chol/PL
      ratio from 0.84 to 1.22. Different phospholipids showed substantially different
      degrees of enrichment with highest enrichments seen for the
      phosphatidylethanolamine fraction (152-fold) and sphingomyelin (101-fold). Thus,
      the phospholipids of the junction enriched membranes consisted mainly of
      ethanolamine glycerophospholipids (37.3%) and sphingomyelin (28.6%), with lesser
      amounts of choline glycerophospholipids (23.5%) and phosphatidylserine (9.2%)
      present. Our data suggest that the MP26 junction enriched membranes of bovine
      lens fiber cells contain differentiated lipid domains, and that cholesterol,
      ethanolamine glycerophospholipids and sphingomyelin are the prevalent boundary
      lipids of the major intrinsic protein in these domains.

PMID- 8856045
TI  - Albumin prevents metabolism of 12-hydroxyeicosatetraenoic acid by leukocytes in
      vitro.
AB  - In the present paper we studied the influence of albumin on the in vitro
      metabolism of 12-hydroxyeicosatetraenoic acid (12-HETE) and arachidonic acid in
      leukocytes and aspirin-treated platelets. In the presence of physiological
      concentrations of albumin, the metabolism of both 12-HETE and arachidonic acid
      was substantially altered, implicating the importance fatty acid binding proteins
      might have on the profile of products formed both in vitro and in vivo. The
      results clearly showed that albumin effectively withdraws arachidonic acid and 12
      HETE from further metabolism by the leukocytes but does not influence the
      conversion of arachidonic acid to 12-HETE by the platelets. Thus, some of the
      hypotheses concerning transcellular metabolism raised from in vitro data within
      the eicosanoid field might have little relevance for the in vivo situation.

PMID- 8856046
TI  - Gangliosides block antigen presentation by human monocytes.
AB  - Gangliosides, immunosuppressive molecules shed by tumor cells, are potent
      inhibitors of monocyte accessory cell function. However, the specific monocyte
      cellular defect caused by gangliosides is unknown. Here we sought to delineate
      whether this abnormality is in the induction of suppressor cells, in
      intracellular antigen processing, or in intercellular antigen presentation. Three
      sets of studies of the tetanus toxoid (TT)-induced lymphoproliferative response,
      which is dependent upon monocyte accessory function, address this issue: (1)
      Antigen (TT)-primed human monocytes incubated with 50-100 microM human brain
      gangliosides for 24-48 h, washed, and then combined with T-cells, were inhibited
      in triggering T-cell proliferation, showing that the effect was occurring after
      antigen processing was complete. (2) T-cell responses to immobilized anti-CD3 or
      to antigen-primed control monocytes in the presence of ganglioside-exposed
      monocytes were unaffected, showing that ganglioside-exposed monocytes did not act
      as suppressor cells. (3) Stimulation by TT peptide fragment 830-843, which does
      not require processing, was completely inhibited by exposure of monocytes to
      gangliosides. These findings identify ganglioside interference with monocyte
      accessory cell function at the level of antigen presentation. We conclude that
      tumor gangliosides may inhibit host anti-tumor cellular immune responses by
      preventing the effective cellular interactions of the antigen-primed monocyte
      with the responding T-lymphocyte.

PMID- 8856047
TI  - The regulation of human immunodeficiency virus type-1 gene expression.
AB  - Despite 15 years of intensive research we still do not have an effective
      treatment for AIDS, the disease caused by human immunodeficiency virus (HIV).
      Recent research is, however, revealing some of the secrets of the replication
      cycle of this complex retrovirus, and this may lead to the development of novel
      antiviral compounds. In particular the virus uses strategies for gene expression
      that seem to be unique in the eukaryotic world. These involve the use of virally
      encoded regulatory proteins that mediate their effects through interactions with
      specific viral target sequences present in the messenger RNA rather than in the
      proviral DNA. If there are no cellular counterparts of these RNA-dependent gene
      regulation pathways then they offer excellent targets for the development of
      antiviral compounds. The viral promoter is also subject to complex regulation by
      combinations of cellular factors that may be functional in different cell types
      and at different cell states. Selective interference of specific cellular factors
      may also provide a route to inhibiting viral replication without disrupting
      normal cellular functions. The aim of this review is to discuss the regulation of
      HIV-1 gene expression and, as far as it is possible, to relate the observations
      to viral pathogenesis. Some areas of research into the regulation of HIV-1
      replication have generated controversy and rather than rehearsing this
      controversy we have imposed our own bias on the field. To redress the balance and
      to give a broader view of HIV-1 replication and pathogenesis we refer you to a
      number of excellent reviews [Cullen, B. R. (1992) Microbiol. Rev. 56, 375-394;
      Levy, J. A. (1993) Microbiol. Rev. 57, 183-394; Antoni, B. A., Stein, S. &
      Rabson, A. B. (1994) Adv. Virus Res. 43, 53-145; Rosen, C. A. & Fenyoe, E. M.
      (1995) AIDS (Phila.) 9, S1-S3].

PMID- 8856048
TI  - The assisted self-association of ATP4- by a poly(amino acid) [poly(Lys)] and its
      significance for cell organelles that contain high concentrations of nucleotides.
AB  - The occurrence of high concentrations of ATP in certain cell organelles prompted
      us to study the self-association of ATP via the concentration dependence of the
      1H-NMR chemical shifts for H2, H8 and H1' in D2O at pD 8.4 (25 degrees C) in the
      range 0.0025-0.4 M in the presence and absence of poly(alpha, L-lysine), where
      [Lys units] was 0.4 M. The experiment in the presence of poly(Lys) was repeated
      at pD 12.1. At pD 8.4, the poly(amino acid) is protonated, i.e. poly(H.Lys)n+,
      whereas at pD 12.1 only approximately 10% of the epsilon-amino groups are
      positively charged. The results in all three systems are consistent with the
      isodesmic model of indefinite non-cooperative stacking. The stacking tendency
      follows the series: ATP4- (K = 1.3 M-1; pD 8.4) < ATP4-/poly(H.Lys)n+ (K = 11.5 M
      1; pD 8.4) > ATP4-/90% poly(Lys)/10% poly(H.Lys)n+ (K = 3.1 M-1; pD 12.1). It is
      evident that poly(H.Lys)n+ assists the association of ATP by a factor of
      approximately 10, and it is suggested that, via its positively charged epsilon
      ammonium groups, poly(H.Lys)n+ acts as a matrix by aligning ATP4- ions via ionic
      interactions with the negatively charged phosphate residues. The intragranular
      concentrations of various constituents of several storage or secretory cell
      organelles, as reported in the literature, are tabulated. The chromaffin granules
      of the adrenal medulla and the dense granules of blood platelets contain
      particularly high concentrations of nucleotides ([ATP] is approximately 0.14 M in
      the chromaffin granules and 0.5 M in the dense granules of rabbit blood
      platelets) and amines, such as epinephrine or 5-hydroxytryptamine. These
      granules, and probably also the storage vesicles of certain neurons (which seem
      to have a similar composition), appear, if the total concentrations of the
      various solutes are considered, to be osmotically unstable, which means that the
      intragranular solutes must be associated. This aggregation is discussed,
      especially with regard to the nucleotides.

PMID- 8856049
TI  - Cloning and biochemical characterisation of an Aspergillus niger glucokinase.
      Evidence for the presence of separate glucokinase and hexokinase enzymes.
AB  - The Aspergillus niger glucokinase gene glkA has been cloned using a probe
      generated by polymerase chain reaction with degenerate oligonucleotides. The DNA
      sequence of the gene was determined, and the deduced amino acid sequence shows
      significant similarity to other eukaryotic hexokinase and glucokinase proteins,
      in particular to the Saccharomyces cerevisiae glucokinase protein. The encoded
      protein was purified from a multicopy glkA transformant, and extensively
      characterised. The protein has a molecular mass of 54536 Da and a pI of 5.2. The
      enzyme has high affinity for glucose (K(m) 0.063 mM at pH 7.5) and a relatively
      low affinity for fructose (K(m) 120 mM at pH 7.5), and in vivo fructose
      phosphorylation by glucokinase is consequently negligible. The configurations at
      C1 and C4 of the substrate appear to be essential for substrate specificity. The
      A. niger glucokinase shows non-competitive inhibition by ADP towards ATP and
      uncompetitive inhibition by ADP towards glucose. The kcal (turnover number)
      decreases rapidly below pH 7.5 (56% at pH 7.0 and 17% at pH 6.5) and this may
      have important implications for the in vivo regulation of activity. In addition,
      proof is provided for the presence of a second hexosephosphorylating enzyme in A.
      niger. This enzyme is probably a hexokinase, since unlike glucokinase, this
      activity is inhibited by trehalose 6-phosphate.

PMID- 8856050
TI  - Phenylalanyl-tRNA synthetase from yeast and its discrimination of 19 amino acids
      in aminoacylation of tRNA(Phe)-C-C-A and tRNA(Phe)-C-C-A(3'NH2).
AB  - For discrimination between phenylalanine and 18 other naturally occurring non
      cognate amino acids by the class II aminoacyl-tRNA synthetase specific for
      phenylalanine, discrimination factors, D, of 190-6300 have been determined from
      kcal and K(m) values. Generally, phenylalanyl-tRNA synthetase is more specific
      than the class II enzymes specific for Lys and Thr, but works with lower accuracy
      than the class I enzymes specific for IIe, Tyr, and Arg. In aminoacylation of
      tRNA(Phe)-C-C-A(3'NH2) discrimination factors D1 vary between 80-1610. Pre
      transfer proof-reading factors II1 are in the range 2.3-74, post-transfer proof
      reading factors II2 in the range 1.0-4.6, showing that pre-transfer proof-reading
      is the main correction step, post-transfer proofreading is less effective or
      negligible. Initial discrimination factors (I1 and I2) caused by differences in
      Gibbs free energies of binding between phenylalanine and non-cognate amino acids
      have been calculated assuming a two-step binding process. Factors I1 can be
      related to hydrophobic-interaction forces depending on accessible surface areas
      of the amino acids, factors I2 scatter about a low mean value and do not show any
      relation to amino acid structures or surfaces, indicating less checking of amino
      acid side chains in the putative second binding step.

PMID- 8856051
TI  - Purification and characterization of a proline-rich antibacterial peptide, with
      sequence similarity to bactenecin-7, from the haemocytes of the shore crab,
      Carcinus maenas.
AB  - Antibacterial peptides are important for non-specific host defence in many
      animals. They have been extensively characterized from mammals, amphibians,
      insects and chelicerates but have not so far been found in crustaceans. Here we
      report the presence of several constitutive antibacterial proteins, active
      against both gram-positive and gram-negative bacteria, in the haemocytes of the
      shore crab, Carcinus maenas. These proteins have molecular masses of > 70 kDa,
      approximately 45 kDa, approximately 14 kDa and 6.5 kDa. The 6.5 kDa peptide has
      been purified to homogeneity by Sep Pak C18 extraction, gel filtration and
      reverse-phase HPLC. Partial N-terminal sequence analysis further shows that it is
      proline rich and shares more than 60% identity in a 28-amino-acid overlap with
      the mature form of bactenecin 7, an antimicrobial peptide from bovine neutrophils
      which belongs to the cathelicidin family of mammalian peptide antibiotics.

PMID- 8856052
TI  - Conformational study of [Met5]enkephalin-Arg-Phe in the presence of
      phosphatidylserine vesicles.
AB  - The interaction of [Met5]enkephalin-Arg.Phe with phosphatidylserine (PtdSer) was
      studied by circular dichroism (CD), two-dimensional nuclear magnetic resonance
      spectroscopy, hybrid distance geometry simulated annealing (DG-SA) and molecular
      dynamics (MD) calculations. The very low solubility of [Met5]enkephalin-Arg-Phe
      and the instability of the solution containing PtdSer vesicles at low pH values
      did not allow us to observe the amide proton resonances in the usual two
      dimensional NMR work. NOESY cross-peaks of protons of side chains from two
      dimensional NMR were converted into distances which were used as restraints for
      modelling with DG-SA and MD. Our results indicate that, in aqueous solutions at
      pH 7.68 [Met5]enkephalin-Arg-Phe exists in the absence of PtdSer as a random
      distribution of conformers, whereas in the presence of PtdSer it adopts
      conformations containing a common orientation of the bonds of C alpha 2, C alpha
      3, C alpha 4, and C alpha 5, although different orientations of the peptide
      planes are consistent with the results. Two of the reported conformers from MD
      simulations are characterized by the presence of a 2<--4 gamma and inverse gamma
      turns centered on Gly3. A gradual decline of order was observed when moving from
      the central moiety of the peptide to both the N-terminus and C-terminus. Finally,
      the DG-SA and MD calculations resulted in a structure such that the orientation
      of the Phe4 and Met5 side chains favours hydrophobic interactions with the apolar
      portion of the PtdSer vesicle to form a hydrophobic cluster. These data support
      the hypothesis of a role of lipids to modify the conformation of [Met5]enkephalin
      Arg-Phe to permit the interactions with the receptor site.

PMID- 8856053
TI  - A spectroscopic study of the structures of latent, active and reactive-center
      cleaved type-1 plasminogen-activator inhibitor.
AB  - Type-1 plasminogen-activator inhibitor (PAI-1) was studied by Fourier-transform
      infrared spectroscopy, far-ultraviolet CD spectroscopy, and fluorescence-emission
      spectroscopy, with the aim to obtain structural information about its active
      form. The spectra of latent, active and reactive-center-cleaved forms of PAI-1
      produced by HT-1080 cells were different. While the cleaved and the latent forms
      were similar with regard to their beta-structure content, comparison of the
      spectra of these forms with the spectra of active PAI-1 suggested a much higher
      degree of unordered structure for the active form compared with the latent and
      reactive-center-cleaved forms than previously assumed. We discuss our results
      with reference to the known three-dimensional X-ray structures of latent PAI-1,
      of reactive-center-cleaved serpins, including reactive-center-cleaved PAI-1, and
      of intact serpins, and with reference to previous results on the differences in
      the affinity of mAbs for the different PAI-1 forms. We interpret our results in
      favor of a global rearrangement of secondary structure during latency transition
      and reactive-center cleavage in PAI-1, not only involving the reactive-center
      loop and parts of beta-sheets A and C, but also the "rear' side of the molecule,
      such as helices H and G. Thus, we suggest flexibility in serpin structural
      elements that were previously regarded as rigid.

PMID- 8856054
TI  - Characterization of the binding properties of protein LG, an immunoglobulin
      binding hybrid protein.
AB  - Protein LG is a 50-kDa hybrid molecule containing four Ig-light-chain-binding
      domains from protein L of Peptostreptococcus magnus and two IgG-Fe-binding
      repeats from streptococcal protein G. Here we analyse the binding of protein LG
      to Ig from several mammalian species. Protein LG was shown to bind human IgG of
      all subclasses and other Ig classes that carry kappa chains. The binding to human
      IgG was only marginally influenced by changes in temperature (4-37 degrees C) or
      salt concentration (0-1.6 M), and was stable over a wide pH range (pH 4-10).
      Protein LG bound to Ig from 11 of 12 mammalian species, including those of
      rabbit, mouse and rat. The affinity constants obtained for the interactions
      between protein LG and polyclonal IgG from rabbit (4.0 x 10(9) M-1), mouse (1.7 x
      10(9) M-1) and rat (1.3 x 10(9) M-1) were similar to the value previously
      reported for the interaction between the hybrid protein and human polyclonal IgG
      (5.9 x 10(9) M-1). The interaction between protein LG and a mouse IgG mAb was not
      influenced by the presence of the specific protein antigen, nor was the binding
      of this antibody to its ligand affected by protein LG. Inhibition experiments
      demonstrated that the Ig-binding site of one of the fusion partners retained its
      ligand-binding capacity when the other component was occupied. Protein LG
      selectively absorbed 85-90% of the total Ig present in human and rabbit sera and
      75-80% of the Ig in sera from mouse and rat. Human serum depleted of C1q, factor
      D and properdin and preabsorbed by protein LG could be used as a source for other
      complement factors. These data demonstrate that protein LG is a very versatile Ig
      binding protein.

PMID- 8856055
TI  - Probing the domain structure of abrin-a by tryptic digestion.
AB  - Abrin-a is a potent plant toxin that consists of A and B chains linked by a
      disulfide bond. The abrin-a A chain (AaTA) has N-glycosidase activity while the
      abrin-a B chain (AaTB) has galactose-binding activity. By partial tryptic
      digestion, the domain structure of abrin-a was investigated. Seven tryptic
      fragments with molecular masses greater than 3500 Da were isolated and
      characterized. One fragment, designated T-21 and consisting of 153 amino acid
      residues, contained the major part of the second domain of AaTB and, after cross
      linking of T-21 with glutaraldehyde, the reaction product had the same level of
      hemagglutinating activity as native abrin. When the T-21 fragment was conjugated
      with AaTA, the conjugate inhibited protein biosynthesis in HeLa cells. This
      suggests that the T-21 fragment is able to bind specifically to cells; its
      conjugate facilitates membrane translocation of AaTA into cells and consequently
      inhibits protein biosynthesis. T-21, with a molecular mass less than AaTB, is
      therefore a potentially useful substance for the preparation of immunotoxins.

PMID- 8856056
TI  - Localization and properties of kinases in clathrin-coated vesicles from zucchini
      hypocotyls.
AB  - Five major polypeptides of 70, 50, 47, 19 and 17 kDa and four minor polypeptides
      (100, 65, 45 and 39 kDa) become phosphorylated when clathrin-coated vesicles
      (CCV) from zucchini hypocotyls are incubated in [gamma 32P]Mg-ATP. After
      dissociation with 0.5 M Tris/HCl the CCV coat polypeptides were subjected to gel
      filtration in order to separate clathrin triskelions from beta-adaptin-containing
      fractions. Only the latter bore kinase activities, with phosphorylated
      polypeptides of 39 kDa in addition to the 50, 19-kDa and 17-kDa polypeptides just
      mentioned. Heparin, an inhibitor of casein kinase II, permitted the
      phosphorylation of only the 19-kDa and 17-kDa polypeptides. Staurosporine, an
      inhibitor of protein kinase c-like activities, prevented the phosporylation of
      the 70-kDa polypeptide. When recombined with the triskelions the beta-adaptin
      fractions achieved the phosphorylation of the 45-kDa and 70-kDa polypeptides.
      Because of its heat stability and calcium-binding properties we interpret the 45
      kDa polypeptide as being a clathrin light chain. Antibodies raised against the 70
      kDa group of heat-shock proteins (Hsp70) recognize a 70-kDa polypeptide in the
      beta-adaptin-containing fractions. Because this polypeptide only phosphorylates
      in the presence of triskelions we consider it to be the uncoating ATPase, which
      is known to aggregate upon dissociation of the CCV coat. Our results therefore
      indicate that zucchini CCV contain a number of phosphorylable polypeptides
      equivalent to the beta, mu and sigma adaptins of bovine brain. Just as in bovine
      brain CCV a casein-kinase-II-like activity is associated with the zucchini CCV
      50/47-kDa polypeptides, further pointing to their identity as plant mu2/mu1
      adaptin equivalents.

PMID- 8856058
TI  - Cello-oligosaccharide hydrolysis by cellobiohydrolase II from Trichoderma reesei.
      Association and rate constants derived from an analysis of progress curves.
AB  - The hydrolysis of soluble cello-oligosaccharides, with a degree of polymerisation
      of 4-6, catalysed by cellobiohydrolase II from Trichoderma reesei was studied
      using 1H-NMR spectroscopy and HPLC. The experimental progress curves were
      analysed by fitting numerically integrated kinetic equations, which provided
      cleavage patterns and kinetic constants for each oligosaccharide. This analysis
      procedure accounts for product inhibition and avoids the initial slope
      approximation. No glucose was detected at the beginning of the reaction
      indicating that only the internal glycosidic linkages are attacked. For
      cellotetraose only the second glycosidic linkage was cleaved. For cellopentaose
      and cellohexaose the second and the third glycosidic linkage from the non
      reducing end were cleaved with approximately equal probability. The degradation
      rates of these cello-oligosaccharides, 1-12 s-1 at 27 degrees C, are about 10-100
      times faster than for the 4-methylumbelliferyl substituted analogs or for
      collotriose. No intermediate products larger than cellotriose were released. The
      degradation rate for cellotetraose were higher than its off-rate, which accounts
      for the processive degradation of cellohexaose. A high cellohexaose/enzyme ratio
      caused slow reversible inactivation of the enzyme.

PMID- 8856057
TI  - 2,4-dioxygenases catalyzing N-heterocyclic-ring cleavage and formation of carbon
      monoxide. Purification and some properties of 1H-3-hydroxy-4-oxoquinaldine 2,4
      dioxygenase from Arthrobacter sp. Ru61a and comparison with 1H-3-hydroxy-4
      oxoquinoline 2,4-dioxygenase from Pseudomonas putida 33/1.
AB  - 1H-3-Hydroxy-4-oxoquinaldine 2,4-dioxygenase (MeQDO) was purified from quinaldine
      grown Arthrobacter sp. Ru61a. It was enriched 59-fold in a yield of 22%, and its
      properties were compared with 1H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase (QDO)
      purified from Pseudomonas putida 33/1. The enzyme-catalyzed conversions were
      performed in an (18O)O2/(16O)O2 atmosphere. Two oxygen atoms of either (18O)O2 or
      (16O)O2 were incorporated at C2 and C4 of the respective substrates, indicating
      that these unusual enzymes, which catalyze the cleavage of two carbon-carbon
      bonds concomitant with CO formation, indeed are 2,4-dioxygenases. Both enzymes
      are small monomeric proteins of 32 kDa (MeQDO) and 30 kDa (QDO). The apparent
      K(m) values of MeQDO for 1H-3-hydroxy-4-oxoquinaldine and QDO for 1H-3-hydroxy-4
      oxoquinoline were 30 microM and 24 microM, respectively. In both 2,4
      dioxygenases, there was no spectral evidence for the presence of a chromophoric
      cofactor. EPR analyses of MeQDO did not reveal any signal that could be assigned
      to an organic radical species or to a metal, and X-ray fluorescence spectrometry
      of both enzymes did not show any metal present in stoichiometric amounts.
      Ethylxanthate, metal-chelating agents (tiron, alpha, alpha'-bipyridyl, 8
      hydroxyquinoline, o-phenanthroline, EDTA, diphenylthiocarbazone,
      diethyldithiocarbamate), reagents that modify sulfhydryl groups (iodoacetamide, N
      ethylmaleimide, p-hydroxymercuribenzoate), and reducing agents (sodium
      dithionite, dithiothreitol, mercaptoethanol) either did not affect 2,4
      dioxygenolytic activities at all or inhibited at high concentrations only. With
      respect to the supposed lack of any cofactor and with respect to the inhibitors
      of dioxygenolytic activities, MeQDO and QDO resemble aci-reductone oxidase (CO
      forming) from Klebsiella pneumoniae, which catalyzes 1,3-dioxygenolytic cleavage
      of 1,2-dihydroxy-3-keto-S-methylthiopentene anion (Wray, J. W. & Abeles, R. H.
      (1993) J. Biol. Chem. 268, 21466-21469; Wray, J. W. & Abeles, R. H. (1995) J.
      Biol. Chem. 270, 3147-3153). 1H-3-Hydroxy-4-oxoquinaldine and 1H-3-hydroxy-4
      oxoquinoline were reactive towards molecular oxygen in the presence of the base
      catalyst potassium-tert.-butoxide in the aprotic solvent N,N-dimethylformamide.
      Base-catalyzed oxidation, yielding the same products as the enzyme-catalyzed
      conversions, provides a non-enzymic model reaction for 2,4-dioxygenolytic release
      of CO from 1H-3-hydroxy-4-oxoquinaldine and 1H-3-hydroxy-4-oxoquinoline.

PMID- 8856059
TI  - 6-Phosphogluconate dehydrogenase from Trypanosoma brucei. Kinetic analysis and
      inhibition by trypanocidal drugs.
AB  - The kinetics of 6-phosphogluconate dehydrogenase from Trypanosoma brucei was
      examined and compared to those of the same enzyme from lamb's liver. Variation of
      kinetic parameters as a function of pH suggests a chemical mechanism similar to
      other 6-phosphogluconate dehydrogenases. The comparison extended to a detailed
      analysis of the effect on enzyme activity by several inhibitors including the
      trypanocidal drugs suramin, melarsoprol and analogues of these compounds. The T.
      brucei enzyme differs significantly from its mammalian counterpart with respect
      to several inhibitors, particularly the substrate analogue 6-phospho-2
      deoxygluconate and the coenzyme analogue adenosine 2',5'-bisphosphate which have
      respectively 170-fold and 40-fold higher affinity for the parasite enzyme.

PMID- 8856060
TI  - Activation and enzyme characteristics of a DNA-restrained phosphatase in
      chromatin-associated complexes.
AB  - DNA-bound polypeptide complexes composed of several non-histone polypeptides that
      resisted harsh DNA deproteinization procedures were characterized. The three
      major polypeptides of these complexes have molecular masses of 62, 52, and 40
      kDa. They constitute supramolecular structures that reside on isolated DNA in
      dense clusters. The supramolecular complexes were released from DNA as globular
      12.8 +/- 0.8-nm particles; these particles were gradually disassembled to form
      smaller supramolecular structures. The DNA-bound complexes comprise of an
      encrypted adenosinetriphosphatase/phosphatase activity, which is a minor but
      intrinsic component of the complexes. The enzyme remained inactive as long as the
      complexes were bound to DNA. However, the enzyme was activated concomitantly with
      the progression of DNA digestion, which indicated that DNA was involved in the
      downregulation of the enzyme. The inactive DNA-restrained complex could not be
      restored in vitro, which indicated its non-trivial nature. Once released from
      DNA, the enzyme was inactivated over a period of several hours. However, in the
      DNA-associated complexes its potential to become activated during DNA digestion
      was conserved for several months. In the activated state, the enzyme showed an
      optimum activity at pH 9.5, was stimulated by Mg2+, inhibited by vanadate and
      EDTA, but was not significantly inhibited by okadaic acid. The active enzyme,
      which consists of two subunits of 56 kDa and 59 kDa, can be released from the
      supramolecular structures by agarose gel electrophoresis. A regulatory mechanism
      therefore exists for the downregulation of this phosphatase by DNA.

PMID- 8856061
TI  - Soyacystatin, a novel cysteine proteinase inhibitor in soybean, is distinct in
      protein structure and gene organization from other cystatins of animal and plant
      origin.
AB  - Cystatins, cysteine proteinase inhibitors, deserve note because of their
      regulatory and protective functions in plant tissues. We isolated both genomic
      DNA and cDNA clones from soybean that encode a cystatin consisting of 245 amino
      acid residues (soyacystatin). It is, while basically similar in sequence to known
      cystatins that are generally in the range of 12-15 kDa, characterized by having
      extremely large extension sequences in both its amino and carboxyl termini. The
      genomic DNA encoding soyacystatin is also unique in that it consists of four
      exons with three introns in its coding regions. The mRNA for soyacystatin is
      distinctly expressed in soybean seeds 2 weeks after flowering. Soyacystatin
      purified from mature soybean seeds had a molecular mass of about 26 kDa on
      SDS/PAGE which suggests that it contains the extension sequences. Papain
      inhibition experiments demonstrate that this endogenous soyacystatin has almost
      the same inhibitory activity as that of its deletion mutant (102 amino acid
      residues) recombinantly produced by truncation of the amino and carboxyl terminal
      extensions, indicating that the occurrence of the extensions does not affect the
      cystatin activity. Immunohistochemical experiments reveal that soyacystatin is
      expressed nearly uniformly in the cotyledons. These results also suggest the
      possible occurrence of a cysteine proteinase as the target enzyme of
      soyacystatin.

PMID- 8856062
TI  - Transient non-native interactions in early folding intermediates do not influence
      the folding kinetics of Escherichia coli tryptophan synthase beta 2 subunits.
AB  - Local structures formed in early intermediates are thought to play a key role in
      orientating the protein folding pathway. Here, we test whether non-native
      interactions formed by eight N-terminal residues in early folding intermediates
      of tryptophan synthase beta chains [Navon, A., Schulze, A. J., Guillou, Y.,
      Zylinksii, C. A., Baleux, F., Expert-Bezancon, N., Friguet, B., Djavadi
      Ohaniance, L. & Goldberg, M. E. (1995) J. Biol. Chem. 270, 4255-4261] influence
      the folding kinetics. The kinetics of in vitro renaturation of wild-type beta
      chains and truncated beta chains lacking residues 2-9 were compared. Each step
      analyzed (molten globule formation, tryptophan shielding, closing up of distant
      residues, and complete renaturation) occurred with similar kinetics in the normal
      and truncated proteins. Thus, non-native interactions formed early during the
      folding of beta chains seem to influence neither the rate and efficiency of the
      complete renaturation, nor the kinetics of the early folding steps, which
      suggests that such non-native early intermediates are poorly stable and highly
      dynamic. This observation is consistent with the current view that productive
      folding should avoid the formation of stable intermediates.

PMID- 8856063
TI  - Contribution of specific disulphide bonds to two epitopes of thyrotropin beta
      subunit associated with receptor recognition.
AB  - In previous studies, we have shown that two epitopes of bovine thyrotropin beta
      subunit that are recognised by the monoclonal antibodies designated mAb 279 and
      mAb 299 are also associated with the receptor-binding site of bovine thyrotropin.
      The present investigation has examined the role of the six disulphide bonds of
      bovine thyrotropin beta-subunit in the conformational stabilisation of these two
      epitopes, and hence assessed the relative contribution that these disulphide
      bonds make to the stabilisation of the receptor-binding region of the beta
      subunit. The experimental procedure involved the production of several bovine
      thyrotropin beta-subunit-related derivatives in which an increasing number of the
      disulphide bonds were selectively reduced with dithiothreitol and alkylated with
      iodoacetic acid. Antibody-binding properties of these derivatives were then
      evaluated in thyrotropin beta-subunit-specific immunoassays based on the use of
      the well characterised mAb 279 and mAb 299, to determine the effect of disulphide
      bond reduction and alkylation on each epitopic specificity. In separate
      experiments, the residual disulphide bonds that remained intact following these
      selective partial reductive alkylation procedures were then fully reduced and
      alkylated with the fluorescent reagent 5-N-[(iodoacetamidoethyl)amino]naphthalene
      1-sulphonic acid. The relative contribution of individual disulphide bonds in the
      stabilisation of each epitope could then be assessed after application of reverse
      phase HPLC peptide mapping methods. Epitope recognition by mAb 279 was not
      dependent on the preservation of the so-called determinant loop Cys88-Cys95
      disulphide bond nor directly involved binding interactions via the Cys2-Cys52,
      Cys27-Cys83, and Cys31-Cys85 disulphide bonds. However, the experimental results
      indicated that the mAb 279 epitope was stabilised by the Cys19-Cys105 and Cys16
      Cys67 disulphide bonds, which is consistent with other data on the role of the C
      terminal region of the thyrotropin beta-subunit in this epitope. In contrast, the
      presence of an intact Cys88-Cys95 disulphide bond was required for the
      stabilisation of the mAb 299 epitope, although the location of this disulphide
      bond is distal to the hairpin loop structure that constitutes the mAb 299
      epitope. These results on the relative contribution of these disulphide bonds are
      also discussed in terms of their relationship to the stabilisation of the
      predicted region of bovine thyrotropin beta-subunit involved in receptor binding.

PMID- 8856064
TI  - Characterization of glycoprotein PAS-6/7 from membranes of bovine milk fat
      globules.
AB  - Glycoprotein components PAS-6 and PAS-7 were purified from bovine milk-fat
      globule membranes and the amino acid sequence of their common polypeptide core,
      PAS-6/7, was determined by peptide and cDNA sequencing. The cDNA encoded a signal
      peptide of 18 amino acid residues and a mature PAS-6/ 7 protein of 409 amino acid
      residues. A cDNA splice variant was identified by reverse transcription/ PCR.
      Results obtained by amino acid analyses, amino-acid-sequence analyses,
      carbohydrate-composition determinations, and MS analyses of glycopeptides
      revealed that both proteins were glycosylated with a carbohydrate structure that
      contained galactose, N-acetylgalactosamine and fucose, and which was O-linked to
      Ser9 in PAS-6 and to Thr16 in PAS-7. In addition, PAS-6 and PAS-7 were N
      glycosylated at Asn41 with a hybrid-type-carbohydrate structure. A high-mannose
      glycan was N-linked to Asn209 of PAS-6. The sequence of PAS-6/7 contained two
      epidermal growth factor (EGF)-like domains in the N-terminal region, the second
      of which contained an RGD cell-adhesion sequence in an extended loop. The EGF
      like domains were followed by a C-terminal tandem repeat, which showed 60-63%
      similarity to the C1-C2 domain of blood-clotting factors V and VIII. The
      disulfide bonds within the C1-C2 domain were identified.

PMID- 8856065
TI  - Different oligomeric states are involved in the allosteric behavior of uracil
      phosphoribosyltransferase from Escherichia coli.
AB  - Uracil phosphoribosyltransferase, catalyzing the formation of UMP and
      pyrophosphate from uracil and 5-phosphoribosyl-alpha-1-diphosphate (PPRibP), was
      purified from an overproducing strain of Escherichia coli. GTP was shown to
      activate the enzyme by reducing K(m) for PPRibP by about fivefold without
      affecting Vmax. When started by addition of enzyme, the reactions accelerated
      over an extended period of time, while enzyme solutions incubated first with GTP
      and PPRibP displayed constant velocities. This indicated that PPRibP and GTP
      influenced the structure of the enzyme. Gel-filtration and sedimentation analyses
      showed that the apparent oligomeric state of uracil phosphoribosyltransferase is
      defined by a dynamic equilibrium between a slowly sedimenting form (dimeric or
      trimeric) that has only a little activity, and a more highly aggregated form
      (pentameric or hexameric), which is more active. It appears that the smaller form
      predominates in the absence of substrates, while the larger form predominates in
      the presence of GTP and PPRibP. Guanosine-3',5'-bis(diphosphate) was found to
      activate the enzyme much like GTP.

PMID- 8856066
TI  - HlyA hemolysin of Vibrio cholerae O1 biotype E1 Tor. Identification of the
      hemolytic complex and evidence for the formation of anion-selective ion-permeable
      channels.
AB  - Hemolysin (HlyA) was concentrated from supernatants of different Vibrio cholerae
      O1 biotype E1 Tor strains by ammonium sulfate precipitation. The concentration of
      the toxin in the supernatants and in the precipitates was quantified using its
      hemolytic activity. The toxin formed a high molecular-mass band (about 220 kDa)
      on SDS/PAGE while the toxin monomer had a molecular mass of 60 kDa when it was
      heated. The addition of the E1 Tor hemolysin oligomers, but not that of the
      monomers, to the aqueous phase bathing lipid bilayer membranes resulted in the
      formation of ion-permeable channels, which had long lifetimes at small voltages.
      The hemolysin channel had a single-channel conductance of 350 pS in 1 M KCl.
      These results defined hemolysin (HlyA) from V. cholerae as a channel-forming
      component with properties similar to other cytolytic toxins. The long lifetime of
      the channel suggested that the channel-forming oligomer did not show a rapid
      association/dissociation reaction. At voltages larger than 50 mV, the hemolysin
      channel was voltage dependent in an asymmetric fashion dependent on the side of
      its addition. The single-channel conductance of the hemolysin (HlyA) from V.
      cholerae O1 biotype E1 Tor channel was a linear function of the bulk aqueous
      conductance, which suggested that the toxin forms aqueous channels with an
      estimated minimum diameter of about 0.7 nm. The hemolysin channel of V. cholerae
      was found to be moderately anion-selective. The pore-forming properties of
      hemolysin (HlyA) from V. cholerae O1 biotype E1 Tor were compared with those of
      aerolysin of Aeromonas sobria and alpha-toxin from Staphylococcus aureus. All
      these cytolytic toxins must probably oligomerize for activity in biological and
      artificial membranes and form anion-selective channels.

PMID- 8856067
TI  - Functional analysis of Glu380 and Leu383 of soybean beta-amylase. A proposed
      action mechanism.
AB  - Soybean beta-amylase, comprising a (beta/alpha)8-barrel core with a mobile loop,
      similar to that of triose phosphate isomerase, was mutated by site-directed
      mutagenesis at residues Glu380 and Leu383. X-ray crystallographic findings
      suggest that Glu380 is the counterpart of the catalytic site (Glu186) and that
      Leu383, located near the active-site cavity, forms an inclusion complex with
      cyclomaltohexaose. Separate substitutions of Glu380 by Gln and Asp completely
      eliminated the activity without inducing any significant changes in the circular
      dichroic spectra nor in the binding affinity for cyclomaltohexaose. Glu380, in
      cooperation with Glu186, therefore, is clearly indispensable for the liberation
      of beta-maltose from starch. Substitutions of Leu383 by Ile and Gln, in contrast,
      led to remarkable increases in the Km values of both mutants when compared to
      that of the non-mutant enzyme. The mutants also showed marked reductions in their
      binding affinities to cyclomaltohexaose. Overall, it would appear that the
      kcat/Km of soybean beta-amylase increases in proportion to the length of the
      substrate molecule, and depends also on the characteristics of the side chain of
      the residue at position 383. Leu383, therefore, may be important for both
      substrate penetration and subsequent retention at the active site. Based on the
      foregoing, we propose an action mechanism of soybean beta-amylase involving the
      interactions of three essential amino acid residues (Asp101, Glu186 and Glu380)
      in concert with Leu383, and assumed an indispensable role for Asp101.

PMID- 8856068
TI  - Further characterization of the peroxisomal 3-hydroxyacyl-CoA dehydrogenases from
      rat liver. Relationship between the different dehydrogenases and evidence that
      fatty acids and the C27 bile acids di- and tri-hydroxycoprostanic acids are
      metabolized by separate multifunctional proteins.
AB  - Recently, we purified five 3-hydroxyacyl-CoA dehydrogenases from isolated rat
      liver peroxisomal fractions. The enzymes were designated I-V according to their
      order of elution from the first column used in the purification procedure.
      Determination of the substrate (L- or D-hydroxyacyl-CoA) stereo-specificity and
      (de)hydratase measurements with the different 3-hydroxyacyl-CoA stereoisomers of
      straight-chain fatty acids and the bile acid intermediate trihydroxycoprostanic
      acid, immunoblotting analysis with antibodies raised against the different
      enzymes and peptide sequencing, all performed on enzymes I-V and molecular
      cloning of enzyme III revealed the following picture. Rat liver peroxisomes
      contain two multifunctional beta-oxidation proteins: (a) multifunctional protein
      1 (the classical multifunctional protein; MFP-1) displaying 2-enoyl-CoA
      hydratase, L-3-hydroxyacyl-CoA dehydrogenase and delta 3, delta 2-enoyl-CoA
      isomerase activity (enzyme IV) and (b) multifunctional protein 2 (MFP-2)
      displaying 2-enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase activity
      (enzyme III). Because of their substrate stereospecificity and because of the
      stereochemical configuration of the naturally occurring beta-oxidation
      intermediates, MFP-1 and MFP-2 appear to be involved in the beta-oxidation of
      fatty acids and bile acids intermediates, respectively. The deduced amino acid
      sequence of the cloned MFP-2 cDNA is highly similar to that of the recently
      described porcine endometrial estradiol 17 beta-dehydrogenase [Leenders, F.,
      Adamski, J., Husen, B., Thole, H. H. & Jungblut, P. W. (1994) Eur. J. Biochem.
      222, 221-227]. In agreement, MFP-2 also displayed estradiol 17 beta-dehydrogenase
      activity, indicating that MFP-2 and the steroid dehydrogenase are identical
      enzymes. MFP-2 is partially cleaved, most probably in vivo, in a estradiol 17
      beta-dehydrogenase/D-3-hydroxyacyl-CoA dehydrogenase that forms a dimeric complex
      (enzyme I) and a hydratase. The physiological significance of enzyme I in bile
      acid synthesis (and steroid metabolism) remains to be determined. MFP-1 (enzyme
      IV) is artefactually cleaved during purification giving rise to 3-hydroxyacyl-CoA
      dehydrogenase V. 3-Hydroxyacyl-CoA dehydrogenase II is a mitochondrial
      contaminant similar to porcine and murine mitochondrial 3-hydroxyacyl-CoA
      dehydrogenase.

PMID- 8856069
TI  - The human IgE germline promoter is regulated by interleukin-4, interleukin-13,
      interferon-alpha and interferon-gamma via an interferon-gamma-activated site and
      its flanking regions.
AB  - Class switching to IgE is preceded by the appearance of epsilon germline
      transcripts, which are induced by interleukin-4 (IL-4) and by IL-13. A 51-bp
      fragment of the human epsilon germline promoter conferred in reporter gene assays
      with the erythroleukemic cell line TF-1 upregulation of transcription by IL-4 or
      IL-13, and repression by interferon-alpha (IFN-alpha) and IFN-gamma. A central
      IFN-gamma activated sequence within the 51-bp fragment was sufficient for
      transcriptional regulation by the cytokines in the absence of its normal flanking
      regions. In contrast, deletion of either upstream or downstream sequences
      abolished repression by IFN-alpha or INF-gamma, but not upregulation by IL-4 or
      IL-13. IL-4 stimulated reporter gene transcription required more than ten times
      higher concentrations than cell proliferation or tyrosine phosphorylation of the
      IL-4 receptor.

PMID- 8856070
TI  - alpha-Oxidation of 3-methyl-substituted fatty acids in rat liver. Production of
      formic acid instead of CO2, cofactor requirements, subcellular localization and
      formation of a 2-hydroxy-3-methylacyl-CoA intermediate.
AB  - alpha-Oxidation of 3-methyl-substituted fatty acids in rat liver was studied in
      intact and permeabilized rat hepatocytes, and in homogenates and subcellular
      fractions. The experiments revealed that the primary end product of alpha
      oxidation is formic acid, which is then converted to CO2. Rates of alpha
      oxidation identical to those observed in intact hepatocytes were obtained in the
      permeabilized hepatocytes and liver homogenates when ATP, Mg2+ and CoA, and Fe2+,
      2-oxoglutarate and ascorbate were added, suggesting that alpha-oxidation involves
      a fatty acid activation reaction and a dioxygenase reaction. Subcellular
      fractionation by differential and density gradient centrifugation demonstrated
      that alpha-oxidation is confined to peroxisomes, which produce formic acid that
      is converted to CO2, mainly in the cytosol. alpha-Oxidation in broken cell
      systems went hand in hand with the formation of a 2-hydroxy-3-methylacyl-CoA
      ester. Formation of the metabolite was strictly dependent on the presence of the
      above-mentioned cofactors, was confined to peroxisomes and was inhibited by
      fenoprofen and propyl gallate, inhibitors of alpha-oxidation in intact cells,
      indicating that the 2-hydroxyacyl-CoA ester is a bona fide intermediate of alpha
      oxidation. Selective omission of cofactors from the reaction mixture and analysis
      of the incubation mixtures for 3-methyl fatty acids, 3-methyl fatty acyl-CoAs and
      their respective 2-hydroxy derivatives revealed that the activation reaction
      precedes the dioxygenase (hydroxylase) reaction. Our experiments demonstrate that
      alpha-oxidation is a peroxisomal process that consists of at least three
      reactions: fatty acid activation, hydroxylation and the reaction(s) involved in
      the release of formic acid.

PMID- 8856071
TI  - Cytochrome c' of Methylococcus capsulatus Bath.
AB  - Cytochrome c' was isolated from the obligate methylotroph Methylococcus
      capsulatus Bath. The native and subunit molecular masses of the cytochrome were
      34.9 kDa and 16.2 kDa, respectively, with an isoelectric pH of 7.0. The amino
      acid composition and N-terminal amino acid sequence were consistent with
      identification of the protein as a cytochrome c'. The electron paramagnetic
      resonance spectrum of the monoheme cytochrome indicated the presence of a high
      spin, S = 5/2, heme center that is diagnostic of cytochromes c'. The optical
      absorption spectra of ferric or ferrous cytochrome c' were also characteristic of
      cytochromes c'. The ferrocytochrome bound carbon monoxide and nitric oxide, but
      not isocyanide, cyanide, or azide. Changes in physical properties due to binding
      of CO or NO to some other c'-type cytochromes have been interpreted as an
      indication of dimer dissociation. In the case of cytochrome c' from M. capsulatus
      Bath, analytical ultracentrifugation of the ferricytochrome, the ferrocytochrome,
      and the ferrocytochrome-CO complex indicate that the changes induced by binding
      of CO are conformational and are not consistent with dimer dissociation. EPR
      spectra show that cytochrome c' was reduced in the presence of hydroxylamine only
      when in a complex with cytochrome P-460. The value of the midpoint potential, Em
      7.0, was -250 mV for cytochrome c' from M. capsulatus Bath, which is well below
      the range of values reported for other cytochromes c'. The values of midpoint
      potentials for cytochrome P-460 (Em 7.0 = -300 mV to -380 mV) and cytochrome C555
      (Em 7.0 = +175 mV to +195 mV) are less than and greater than, respectively, the
      value for cytochrome c' and suggest the possibility that the latter may function
      as an electron shuttle between cytochrome P-460 and cytochrome C555.

PMID- 8856072
TI  - Two subsites on the active center of pig kidney trehalase.
AB  - A kinetic analysis of the active site of pig kidney trehalase was made by
      examining two types of inhibitors that are monosaccharide analogs and cause a
      competitive inhibition of the trehalase. Trehalase hydrolyzes trehalose (alpha-D
      glycopyranosyl alpha-D-glucopyranoside) to give an equimolar mixture of alpha-D
      glucose and, by inversion of configuration, beta-D-glucose. 1,4-Dideoxyl-1,4
      imino-D-arabinitol is considered to be a transition state (glucosyl cation)
      analog, while methyl beta-D-glucoside, 1,5-dideoxy-1,5-imino-D-glucitol (1
      deoxynojirimycin), fagomine, and 1-epivalidamine are considered to be analogs of
      the beta-D-glucose that is derived by hydrolysis of trehalose. These glucosyl
      cation inhibitor and beta-D-glucose analog inhibitors competed with each other at
      the same site on the active center of pig kidney trehalase and were therefore put
      together in one group (group A). Methyl alpha-D-mannoside and 1
      deoxymannojirimycin were also competitive inhibitors of trehalase and competed
      with each other for the same site. However, an inhibitor in group A did not
      compete with the methyl alpha-D-mannoside or 1,5-dideoxy-1,5-imino-D-mannitol (1
      deoxymannojirimycin). Thus these latter two inhibitors were placed in group B.
      These results support the hypothesis that the active center of trehalase may
      comprise two subsites, one for catalysis and one for recognition, that act
      separately on each of the glucose of the trehalose. The catalysis site requires
      the correct D-glucose configuration at carbons 2, 3, 4, and 5 or a good
      superimposition onto the glucosyl cation intermediate. The C2 equatorial OH group
      of a glucopyranosyl residue appears to be important for binding at the catalytic
      site since 1-deoxynojirimycin is more tightly bound by two orders of magnitude
      over its 2-deoxy derivative, fagomine. The beta-D-glucose and glucosyl cation
      analogs best fit this site. The recognition site is compatible with D-glucose and
      its analogs bearing the alpha configuration at the anomeric position. alpha-D
      Mannose analogs are much more tightly bound than the corresponding D-gluco
      compound at this site. The extremely high affinity (Ki = 0.52 nM) of
      validoxylamine A, a mimic of the substrate in the transition state, derives from
      the synergistic interactions of two cyclitol units with two subsites. The value
      obtained by multiplying the Ki (1.2 microM) for 1-epivalidamine times that for 1
      deoxymannojirimycin (Ki = 0.39 mM) is very close to that for validoxylamine A.
      The results described here may be applicable to other trehalase molecules.

PMID- 8856074
TI  - Restoration of Clostridium difficile toxin-B-inhibited phospholipase D by
      phosphatidylinositol 4,5-bisphosphate.
AB  - Receptor signalling to phospholipase D (PLD) in human embryonic kidney (HEK)
      cells stably expressing the m3 muscarinic acetylcholine receptor apparently
      involves Rho proteins. Since phosphatidylinositol 4,5-bisphosphate
      [PtdIns(4,5)P2] has been recognized as an essential cofactor for PLD activity and
      since activated Rho proteins have been reported to stimulate the synthesis of
      PtdIns(4,5)P2, we studied whether in HEK cells PLD activity is regulated by
      PtdIns(4,5)P2 and, in particular, whether PtdIns(4,5)P2 can restore PLD activity
      inhibited by Clostridium difficile toxin B, which inactivates Rho proteins.
      Addition of MgATP to permeabilized HEK cells increased basal PLD activity and
      potentiated PLD stimulation by the stable GTP analogue, guanosine 5'-[gamma
      thio]triphosphate (GTP[S]), concomitant with a large increase in PtdIns(4,5)P2.
      On the other hand, neomycin, which binds to PtdIns(4,5)P2, inhibited basal and
      GTP[S]-stimulated PLD activities. Addition of PtdIns(4,5)P2 increased PLD
      activity in HEK cell membranes by 2-3-fold, whereas various other phospholipids
      were ineffective. Prior treatment of HEK cells with toxin B reduced the level of
      PtdIns(4,5)P2, measured either in intact cells or in membrane preparations, by
      about 40%. In membranes of toxin-B-treated cells, basal and GTP[S]-stimulated PLD
      activities were reduced, when measured with exogenous phosphatidylcholine as
      enzyme substrate. Inclusion of PtdIns(4,5)P2 with phosphatidylcholine in the
      substrate vesicles or addition of PtdIns(4,5)P2 fully restored basal and GTP[S]
      stimulated PLD activities in membranes of toxin-B-treated cells. In conclusion,
      the data indicate that PtdIns(4,5)P2 is an essential cofactor for PLD activity in
      HEK cells and that inhibition of PLD activity by the Rho-inactivating toxin B is
      apparently caused by depletion of the PLD cofactor, PtdIns(4,5)P2.

PMID- 8856073
TI  - Modulation of the activity of the human cholesteryl ester transfer protein by
      carboxylated derivatives. Evidence for 13-cis-retinoic acid as a potent activator
      of the protein's activity in plasma.
AB  - The influence of palmitic acid, 13-cis-retinoic acid, all-trans-retinoic acid,
      and all-trans-retinol on the activity of the human cholesteryl ester transfer
      protein (CETP) was evaluated either in total human plasma supplemented with a
      tracer dose of 3H-labeled cholesteryl-ester-containing high-density lipoprotein
      sub-fraction 3 ([3H]CE-HDL3), or in reconstituted mixtures containing [3H]CE
      HDL3, isolated low-density lipoproteins (LDL), and purified CETP. In
      reconstituted mixtures, all the carboxylated derivatives increased progressively
      and significantly the transfer of 3H-labeled cholesteryl esters from [3H]CE-HDL3
      towards LDL in the 20-100 microM concentration range. Under identical
      experimental conditions, CETP activity was only minimally modified in the
      presence of all-trans-retinol. When present at a concentration of 60, 80, or 100
      microM, 13-cis-retinoic acid was a significantly more potent activator of CETP
      activity than all the other derivatives studied (P < 0.01 in all cases). In
      contrast to observations made with reconstituted mixtures, only 13-cis-retinoic
      acid, but not palmitic acid, was able to induce a significant, concentration
      dependent stimulation of CETP activity in total human plasma. In fact,
      differences in the ability of 13-cis-retinoic acid and palmitic acid to modulate
      the plasma cholesteryl ester transfer reaction were linked to their relative
      affinity for albumin and lipoprotein substrates: fatty-acid-poor albumin reduced
      CETP activity to a significantly greater extent in reconstituted mixtures
      containing palmitic acid than in reconstituted mixtures containing 13-cis
      retinoic acid (P < 0.01 for all the incubation mixtures in the 1-10 g/l albumin
      concentration range); palmitic acid presented a markedly lower ability to
      increase the electrophoretic mobility of LDL and HDL fractions in total plasma
      than 13-cis-retinoic acid. In support of a key role of the negatively charged
      carboxylic group of 13-cis-retinoic acid in upregulating CETP activity,
      cholesteryl ester transfer rates correlated positively with the electrophoretic
      mobility of LDL (r = 0.98; P < 0.0002) and HDL (r = 0.96; P < 0.0008) in total
      plasma supplemented with the carboxylated compound. It is concluded that 13-cis
      retinoic acid can upregulate the CETP-mediated cholesteryl ester transfer
      reaction both in reconstituted mixtures containing isolated lipoproteins and
      purified CETP, and in total normolipidemic human plasma.

PMID- 8856075
TI  - Microsomal triacylglycerol transfer protein prevents presecretory degradation of
      apolipoprotein B-100. A dithiothreitol-sensitive protease is involved.
AB  - The role of microsomal triacylglycerol transfer protein (MTP) in the secretion of
      apolipoprotein B-100 (apoB-100) has been studied using an inhibitor of MTP: 4'
      bromo-3'-methylmetaqualone. In vitro, this compound inhibits trioleoylglycerol
      transfer between lipid vesicles mediated by MTP with an IC50 of 0.9 microM
      whereas it does not inhibit the lipid transfer mediated by the cholesteryl ester
      transfer protein. In HepG2 cells, 4'-bromo-3'-methylmetaqualone inhibits the
      secretion of apoB-100 with an IC50 of 0.3 microM, without affecting the secretion
      of several other proteins like apoA-I or albumin. Moreover, there is no
      accumulation of apoB-100 in treated cells. Oleic acid, which increases apoB-100
      secretion, only slightly modifies the IC50 of 4'-bromo-3'-methylmetaqualone (0.5
      microM). The latter has no effect on the synthesis of major lipids within the
      cell, but decreases the secretion of triacylglycerol into apoB-100-containing
      lipoproteins. Pulse/chase experiments reveal that 4'-bromo-3'-methylmetaqualone
      acts on apoB-100 production either at the co-translational or post-translational
      level. The cysteine protease inhibitor N-acetyl-leucyl-leucyl-norleucinal does
      not protect apoB-100 from the 4'-bromo-3'-methylmetaqualone effect but seems to
      be involved in a later step of apoB-100 intracellular degradation. By contrast,
      dithiothreitol can totally reverse the effect of the MTP inhibitor on apoB-100
      production. The mechanism of MTP-mediated lipid assembly with apoB-100 is
      discussed.

PMID- 8856076
TI  - Experimental verification of the secondary structures of guide RNA-pre-mRNA
      chimaeric molecules in Trypanosoma brucei.
AB  - RNA editing in kinetoplastid organisms is an RNA-processing reaction that adds
      and deletes U nucleotides at specific sites in mitochondrial pre-mRNAs. The
      edited sequence is specified by guide RNAs and the processing presumably occurs
      within a high-molecular-mass ribonucleoprotein complex containing several
      enzymatic activities. Although the mechanism is not currently known, potential
      intermediates or by-products of the editing process are chimaeric RNAs where
      guide (g) RNAs are covalently attached, via their non-encoded U-tail, to their
      cognate pre-mRNAs. We determined the secondary structures of three different
      ATPase 6 chimaeras of Trypanosoma brucei using a set of structure-sensitive
      chemical and enzymatic probes. The experiments revealed a bipartite domain
      structure consisting of a gRNA/pre-mRNA interaction hairpin and an independently
      folding mRNA stem/loop in all three RNAs. The connecting U-tail was a determinant
      for the length of the interaction stems with the oligo(U) nucleotides base
      pairing to internal gRNA sequences. The probed structures have calculated delta
      G27o values of -92 kJ/ mol to -134 kJ/mol, somewhat less stable than the
      predicted minimal free energy structures and support previously proposed models
      for the interaction between gRNAs and pre-mRNAs. Optical melting studies
      indicated additional, higher order structural features for all three molecules
      with four defined melting transition between 10 degrees C and 90 degrees C. A
      comparison of CD spectra in the absence and presence of mitochondrial protein
      extracts demonstrated no gross structural changes of the RNA structures induced
      by the association with polypeptides.

PMID- 8856077
TI  - Alternative processing of the tryptophanyl-tRNA synthetase mRNA from interferon
      treated human cells.
AB  - We have analysed the structure of mRNA isoforms of the human gene encoding
      tryptophanyl-tRNA synthetase (Trp-tRNA synthetase) expressed in the epithelial
      CaOv cells and MT-4 lymphocytes. The Trp-tRNA synthetase gene is induced by
      interferon-gamma in both lines and, in MT-4 lymphocytes, also by interferon
      alpha. Four Trp-tRNA synthetase mRNA isoforms have different combinations of the
      first exons IA, IB and II. Two transcription initiation sites (P1 and P2) were
      detected 90 bp from each other. Processing of the primary transcript initiated
      from the P1 start site generates the mRNA isoform where exon IA joins to exon II.
      The other three isoforms are produced by alternative splicing of the primary
      transcript produced from the P2 start site. Isoform 2 has a 3'-end fragment of
      exon IA joined to exon II. Isoform 3 contains exons IA and IB. Isoform 4 contains
      exon IA and exon III and lacks exon II encoding the N-terminus of the Trp-tRNA
      synthetase. Therefore, the two primary transcripts of the Trp-tRNA synthetase
      gene differ only in the 5' flank sequence between P1 and P2, and this fragment
      regulates their processing. Both interferon-alpha and interferon-gamma induce
      exon IA-containing and exon IB-containing isoforms of the Trp-tRNA synthetase
      mRNA.

PMID- 8856079
TI  - Replacement of Ser657 of protein kinase C-alpha by alanine leads to premature
      down regulation after phorbol-ester-induced translocation to the membrane.
AB  - Protein kinase C (PKC) is activated at the cell membrane by interacting with both
      the acidic lipid phosphatidylserine and the second messenger diacylglycerol. A
      direct activation of the kinase is also possible by substituting diacylglycerol
      with phorbol esters such as the tumor promoting agent 12-O-tetradecanoylphorbol
      13-acetate (TPA). Transphosphorylation of the activation loop followed by
      autophosphorylation at sites located on various domains of the protein have been
      suggested to be required as permissive activation of the alpha and beta isoforms
      of PKC [Cazaubon, S., Bornancin, F. & Parker, P. (1994) Biochem. J. 301, 443-448;
      Keranen, L. M., Dutil, E. M. & Newton, A. C. (1995) Curr. Biol. 5, 1393-1403].
      Ser657, located near the C-terminus of PKC-alpha, represents a site which is very
      conserved among the members of the PKC protein family. Circumstantial evidence
      suggested that this residue represents a possible site of phosphorylation. The
      conversion of Ser657 to alanine caused a 70% loss of the catalytic activity as
      well as a drastically increased down regulation upon translocation of this
      isozyme to the membrane when induced by phorbol ester. The faster electrophoretic
      mobility of the mutant protein compared to that of the wild-type enzyme suggested
      that Ser657 represents a phosphorylation site.

PMID- 8856078
TI  - Primary structure and characterization of an exopolygalacturonase from
      Aspergillus tubingensis.
AB  - From the culture fluid of the hyphal fungus Aspergillus tubingensis, an
      exopolygalacturonase with a molecular mass of 78 kDa, an isoelectric point in the
      pH-range 3.7-4.4 and a pH optimum of 4.2 was purified. The enzyme has been
      characterized as an exopolygalacturonase [poly(1,4-alpha-D
      galacturonide)galacturonohydrolase] that cleaves monomer units from the non
      reducing end of the substrate molecule. K(m) and Vmax for polygalacturonic acid
      hydrolysis were 3.2 mg ml-1 and 3.1 mg ml-1 and 255 U mg-1 and 262 U mg-1 for the
      wild-type and recombinant enzymes, respectively. The kinetic data of
      exopolygalacturonase on oligogalacturonates of different degree of polymerization
      (2-7) were interpreted in terms of a subsite model to obtain more insight into
      catalysis and substrate binding. On oligogalacturonates of different degrees of
      polymerization (2-7), the Michaelis constant (K(m)) decreased with increasing
      chain length (n). The Vmax value increased with chain length up to n = 4, then
      reached a plateau value. The enzyme was competitively inhibited by galacturonic
      acid (Ki = 0.3 mM) as well as by reduced digalacturonate (Ki = 0.4 mM). The
      exopolygalacturonase gene (pgaX) was cloned by reverse genetics and shows only
      13% overall amino acid sequence identity with A. niger endopolygalacturonases.
      The exopolygalacturonase is most related to plant polygalacturonases. Only four
      small stretches of amino acids are conserved between all known endogalacturonases
      and exopolygalacturonases. Expression of the pgaX gene is inducible with
      galacturonic acid and is subject to catabolite repression. A fusion between the
      promoter of the A. niger glycolytic gene encoding pyruvate kinase and the pgaX
      coding region was used to achieve high level production of exopolygalacturonase
      under conditions where no endopolygalacturonases were produced.

PMID- 8856080
TI  - Molecular-dynamics simulation of domain movements in aspartate aminotransferase.
AB  - Mitochondrial aspartate aminotransferase is a homodimeric protein with 2 x 402
      amino acid residues. The enzyme in solution undergoes ligand-induced and
      syncatalytic conformational changes which appear to correspond to shifts in the
      equilibrium between the crystallographically defined open and closed
      conformation. In the closed conformation, the small domain of each subunit has
      rotated as a rigid body by 13 degrees and 14 degrees towards the large coenzyme
      binding domain and has closed the active-site pocket. Molecular dynamics
      simulations at 300 K of 120-ps duration were started from the crystal structures
      of the unliganded pyridoxal form (open form) of the dimeric enzyme and the 2
      methylaspartate-liganded closed form in which the 2-methyl group had been
      removed. Both structures contained the crystal water molecules and were placed in
      a 5-A shell of water. The rms fluctuations of the individual C alpha atoms during
      the simulations agreed well with the corresponding B factors of the crystal
      structures. Superposition of the initial structures and the average structures of
      the last 20 ps showed in both simulations extensive C alpha deviations in the
      case of the whole subunit but much smaller changes in the individual large and
      small domains, indicating a movement of the two domains relative to each other.
      In the simulation of the open form, superposition of the large domains made
      evident a displacement of the small domain towards its position in the closed
      crystal structure, which can be described by a rotation of the small domain by
      about 13 degrees around the twofold symmetry (z) axis. A significantly less
      extensive rearrangement of parts of the small domain, i.e. a rotation of about 5
      degrees around the z axis, was observed in the simulation of the substrate
      liganded enzyme (closed form) which, in contrast to the open form, showed only
      small conformational changes around the active site. In both simulations an
      additional rotation of the small domain by 9 degrees around the x axis occurred.
      The actual domain movement is estimated to occur in a time range at least two
      orders of magnitude larger than the simulation time of 120 ps. Apparently, the
      surface tension of the unrestrained nonspherical shell of water accelerates the
      simulated conformational change which, however, quite closely imitates the
      geometric features of the extensive movement of the small domains (each
      approximately 130 residues).

PMID- 8856081
TI  - The purification and characterization of the catalytic domain of Src expressed in
      Schizosaccharomyces pombe. Comparison of unphosphorylated and tyrosine
      phosphorylated species.
AB  - The catalytic domain of chicken Src including the C-terminal tail (Src-CD), has
      been expressed in Schizosaccharomyces pombe and purified to homogeneity. The
      expressed protein is a mixture of unphosphorylated (80%) and mono-phosphorylated
      (20%) species, that can be separated from each other by Mono Q chromatography. By
      a novel mass spectrometric method that utilizes parent ion scans of unseparated
      peptide mixtures, we found that the mono-phosphorylated form is phosphorylated
      either at Tyr416 or at Tyr436. The stability of Src-CD is comparable to the wild
      type protein. Src-CD auto-phosphorylates and efficiently phosphorylates substrate
      peptides and proteins. Auto-phosphorylation occurs by an intermolecular mechanism
      and is completely inhibited by an excess of substrate peptide. Kinetic
      measurements for two exogenous substrates, the Src substrate peptide
      (AEEEIYGEFEAKKKK) and denatured enolase, showed that the overall activity (kcat)
      of the Src-CD molecule is about 10 times higher than that of wild-type Src. The
      kcat values for phosphorylation of the Src substrate peptide are similar for the
      unphosphorylated and monophosphorylated Src-CD (50 min-1), but the apparent K(m)
      values differ significantly (approximately 3 microM and 10 microM, respectively).
      Therefore, at low substrate concentrations in vitro the mono-phosphorylated form
      is more active, in agreement with the importance of Tyr416 for in vivo activity.
      The apparent K(m) values of the mono-phosphorylated Src-CD and wild-type Src for
      the Src substrate peptide and enolase are similar, indicating that, under these
      conditions, the kinase domain is mainly responsible for substrate binding.

PMID- 8856082
TI  - A synthetic peptide from the human immunodeficiency virus type-1 integrase
      exhibits coiled-coil properties and interferes with the in vitro integration
      activity of the enzyme. Correlated biochemical and spectroscopic results.
AB  - Integration of the human immunodeficiency virus (HIV-1) DNA into the host genome
      is catalysed by a virus-encoded protein integrase. Here, we report some of the
      structural and functional properties of two synthetic peptides: integrase-(147
      175)-peptide reproducing the residues 147-175 (SQGVVESMNKELK159KIIGQVRDQAEHLKTAY)
      of the HIV-1 integrase, and [Pro159] integrase-(147-175)-peptide where the lysine
      159 is substituted for a proline. Circular dichroism revealed that both peptides
      are mostly under unordered conformation in aqueous solution, contrasting with the
      alpha-helix exhibited by residues 147-175 in the protein crystal structure. In a
      weak alpha-helix-promoting environment, integrase-(147-175)-peptide self
      associated into stable coiled-coil oligomers, while [Pro159] integrase-(147-175)
      peptide did not. This property was further confirmed by cross-linking
      experiments. In our in vitro experiments, only integrase-(147-175)-peptide was
      able to reduce the integration activity of the enzyme. We propose that the
      inhibitory activity shown by integrase-(147-175)-peptide is dependent on its
      ability to bind to its counterpart in integrase through a peptide-protein coiled
      coil structure disturbing the catalytic properties of the enzyme.

PMID- 8856083
TI  - Interaction of human immunodeficiency virus type 1 reverse transcriptase with
      primer tRNALys3 and affinity modification of the enzyme by tRNALys3 derivatives.
AB  - The recognition of primer tRNA by retroviral reverse transcriptase is a crucial
      step in the replication of retroviruses. In the complex formed by HIV-1 reverse
      transcriptase and its natural primer tRNALys3, the heterodimeric enzyme, p66/p51,
      binds two molecules of tRNALys3 with different affinities. The same complex but
      in the presence of a non-complementary template, poly(A), gave higher Kd values.
      Preincubation of the reverse transcriptase with tRNA at concentrations comparable
      to the Kd2 value results in different levels of stimulation of the DNA polymerase
      activity: 300% in the absence and 70-80% in the presence of poly(A). The
      activation of the catalytically active p66 subunit is most probably mediated
      through tRNA interaction with the site of reverse transcriptase presenting the
      lower affinity. In this article, we describe the results obtained with new
      chemically reactive derivatives of tRNA bearing three or seven hydrophobic
      residues. Incubation of reverse transcriptase with tRNA derivatives, in the
      presence or absence of poly(A), leads to covalent binding of the reagents and
      inactivation of the enzymatic activity. However, during the initial step of the
      modification reaction, in the absence of poly(A), a slight stimulation of reverse
      transcriptase by tRNA derivatives took place, followed by a decrease in the
      enzymatic activity due to the covalent binding of tRNA derivatives to reverse
      transcriptase. In the presence of poly(A), enzyme inactivation occurs according
      to pseudo-first-order reaction kinetics. The affinities of tRNA derivatives for
      the p66/p51 heterodimer estimated from affinity modification data (Kd values) and
      from the inhibition of polymerization reaction (Ki values) were determined. Each
      analog of tRNA presented two Kd and two Ki values.

PMID- 8856084
TI  - Kinetic evidence for protein complexes between thioredoxin and NADP-malate
      dehydrogenase and presence of a thioredoxin binding site at the N-terminus of the
      enzyme.
AB  - The kinetics of activation of NADP-malate dehydrogenase (MDH; EC 1.1.1.82) from
      soybean and spinach leaves by the chloroplast thioredoxins isolated from the same
      plants, by the corresponding storage forms of the soybean chloroplast
      thioredoxins from soybean seeds, and by the bacterial Escherichia coli
      thioredoxin have been studied. The Hill equation has been applied to evaluate the
      saturation kinetics. The observed variable thioredoxin saturation characteristics
      (Vmax 0.37-14.5 mumol NADPH min-1 mg enzyme-1; K0.5 0.15-1.33 microM; Hill
      coefficient h 0.90-3.04) indicate that the activation of NADP-MDH depends
      strongly on the individual thioredoxin used. Thus, thioredoxin action is not
      solely due to simple reductive activation of the NADP-MDH. Specific thioredoxin
      complex formation between thioredoxin and NADP-MDH must be included into the
      mechanism of the activation process. To study the regulatory consequences of the
      specific thioredoxin/NADP-MDH complexes we investigated the saturation kinetics
      of the substrates NADPH and oxaloacetate in presence of different concentrations
      of each individual thioredoxin species. The kinetic characteristics of the
      substrates (S0.5, Vmax, and Hill coefficients h) varied individually in response
      to the different thioredoxin species substantiating our model of thioredoxin/
      NADP-MDH complex formation. Aminopeptidase-K-truncated pea NADP-MDH has been used
      to demonstrate that the N-terminal 37 amino residues are involved in providing a
      specific thioredoxin binding site. The fact that the versatile light-dependent
      regulation of numerous enzyme activities by only two thioredoxin species in
      chloroplasts cannot be accomplished without the formation of thioredoxin/target
      enzyme complexes is discussed in detail.

PMID- 8856085
TI  - Polydispersity in sulfation profile of oligosaccharide alditols isolated from the
      protein-linkage region and the repeating disaccharide region of chondroitin 4
      sulfate of bovine nasal septal cartilage.
AB  - Proteoglycans of bovine nasal septal cartilage bear predominantly chondroitin 4
      sulfate. After exhaustive chondroitinase ABC digestion of a chondromucoprotein
      preparation rich in proteoglycans and subsequent reductive beta-elimination, five
      hexasaccharide alditols were isolated from the glycosaminoglycan-protein linkage
      region. They were analyzed by enzymatic digestion in conjunction with HPLC and by
      one-dimensional and two-dimensional 1H-NMR spectroscopy. They share the
      conventional core saccharide structure delta 4.5HexA alpha 1-3GalNAc beta 1-4GlcA
      beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol (where delta 4.5HexA is 4,5-unsaturated
      hexuronic acid), but have different sulfation profiles. One compound (I) does not
      contain sulfate. Two of the three monosulfated compounds (II and III) have an O
      sulfate group at either C6 or at C4 of the GalNAc residue. The other monosulfated
      compound (IV) is hitherto unreported and has a O-sulfate at C4 of the Gal residue
      preceding the GlcA residue, whereas the GalNAc is not sulfated. The disulfated
      compound (V) has sulfate groups at C4 of both the Gal residue preceding GlcA and
      the GalNAc residue. The molar ratio of compounds I-V is 38.3:5.9:43.0:1.6:11.2.
      The structural heterogeneity of these hexasaccharide alditols reflects the
      polydispersity in the linkage region of the chondroitin sulfate chains. In
      addition, two trisaccharide and two tetrasaccharide alditols derived from the
      repeating disaccharide region of the chondroitin sulfate chains were also
      isolated. Their structures were unambiguously determined by enzymatic analysis
      and by 1H-NMR spectroscopy as delta 4.5HexA alpha 1-3GalNAc(4-O- or 6-O
      sulfate)beta 1-4GlcA-ol and delta 4.5HexA alpha 1-3GalNAc(4-O- or 6-O-sulfate)
      beta 1-4GlcA beta 1-3GalNAc(4-O-sulfate)-ol, respectively.

PMID- 8856086
TI  - Transbilayer phosphatidylethanolamine movements in the yeast plasma membrane.
      Evidence for a protein-mediated, energy-dependent mechanism.
AB  - Aminophospholipid movements in the plasma membrane of higher eukaryotic cells
      seem to be regulated by an ATP-dependent, protein-mediated process. To examine
      whether similar mechanisms exist in yeast cells, we have analysed
      phosphatidylethanolamine (PtdEtn) distributions in Saccharomyces cerevisiae
      (A184D) cells under a variety of conditions, with trinitrobenzenesulfonic acid
      and fluorescamine as the external membrane probes. The levels of external PtdEtn
      in the intact cells were reduced to about 50% by pretreatment of the cells with
      inhibitors of mitochondrial ATP synthesis, ATPase inhibitors or protein
      sulfhydryl-group-modifying reagents, or by depletion of the cells of ATP by
      metabolic starvation. The levels of external PtdEtn could be restored to normal
      by repletion of the energy-depleted cells with ATP. Furthermore, treatment of the
      energy-depleted cells with sulfhydryl-modifying reagents did not cause further
      reduction in the external PtdEtn levels but decreased the accessibility of PtdEtn
      to fluorescamine after restoration of the cellular ATP levels to normal in these
      cells. These results demonstrate an involvement of an ATP-dependent, protein
      mediated process(es) in the regulation of the PtdEtn distribution across the
      plasma-membrane bilayer of yeast cells. The results are discussed with regard to
      possible models that can generate and maintain the transbilayer phospholipid
      asymmetry in the yeast plasma membrane.

PMID- 8856088
TI  - Developmental change of megakaryocyte maturation and DNA ploidy in human fetus.
AB  - Megakaryocytes in fetal livers obtained from 30 water-balloon aborted normal
      fetuses of 3 to 6 months' gestation, in the bone marrow from the same 30 fetuses,
      and another 9 fetuses of 7 to 8 months' gestation and in the normal bone marrow
      of adults were analyzed by immunocytochemical staining for size and maturation
      stage distribution and by flow cytometry for ploidy distribution simultaneously.
      In human fetuses, megakaryocytes showed a shift during ontogenesis from smaller
      towards larger size and from less mature towards a more mature stage with
      advancement of gestation. This was accompanied by a significant progressive shift
      to higher ploidy. However, the proportions (78.64%) of hypoploidy (< or = 8N)
      megakaryocytes in bone marrow of 7-8 months' gestation fetuses was still much
      higher than that (33.32%) in human adults (p < 0.05), with the proportion of
      hyperploidy (> or = 16N) megakaryocytes lower than that (67.86%) in human adults.
      This result indicated that megakaryocyte polyploidization may be retarded or
      inhibited during development.

PMID- 8856087
TI  - Solubilization and characterization of a thyroid Ca(2+)-dependent and NADPH
      dependent K3Fe(CN)6 reductase. Relationship with the NADPH-dependent H2O2
      generating system.
AB  - The thyroid plasma membrane contains a Ca(2+)-regulated NADPH-dependent H2O2
      generating system which provides H2O2 for the thyroid-peroxidase-catalyzed
      biosynthesis of thyroid hormones. The molecular nature of the membrane-associated
      electron transport chain that generates H2O2 in the thyroid is unknown, but
      recent observations indicate that a flavoprotein containing a FAD prosthetic
      group is involved. Solubilization was reinvestigated using 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps), Triton X-100, and
      high salt concentrations. Chaps eliminated about 30% of the proteins, which
      included a ferricyanide reductase, without affecting the H2O2-generating system.
      Similarly, Triton X-100 alone did not extract the NADPH oxidase. An NADPH-oxidase
      activity, which was measured in the presence of the artificial electron acceptor
      potassium ferricyanide, was solubilized by increasing the ionic strength to 2 M
      KCl. This NADPH-ferricyanide reductase activity was shown to belong to the H2O2
      generating system, although it did not produce H2O2. It was still Ca2+ dependent
      and H2O2 production was restored by decreasing the ionic strength by overnight
      dialysis. No H2O2 production activity was detected after sucrose density gradient
      centrifugation of the dialyzed solubilized enzyme, but a well-defined peak of
      NADPH oxidation activity with a sedimentation coefficient of 3.71 S was found in
      the presence of K3Fe(CN)6. These results suggest that some unknown component(s)
      (phospholipid or protein) is removed during sucrose density gradient
      centrifugation. Finally, thyrotropin, which induces NADPH oxidase and regulates
      H2O2 production in porcine thyrocytes in primary culture, also induced the NADPH
      K3Fe(CN)6 reductase activity associated with the H2O2-generating system. Thus,
      this enzyme seems to be another marker of thyroid differentiation.

PMID- 8856089
TI  - Effects of combinations of stem cell factor and hemin on erythropoiesis after
      azidothymidine treatment of immunosuppressed mice.
AB  - Recombinant cytokines such as stem cell factor (SCF) are currently being tested
      for the ability to ameliorate 3'azido-3'deoxythymidine (AZT) induced anemia in
      AIDS patients. Recently, we demonstrated that SCF and hemin in vitro greatly
      increased the resistance of burst-forming units erythroid (BFU-E) to AZT. We
      therefore attempted to ameliorate AZT-induced anemia in vivo using SCF and hemin
      in immunodeficient LP-BM5 infected (MAIDS) mice. SCF and hemin were administered
      with oral AZT for 3 wk and the effects on erythropoiesis examined. Hemin
      significantly increased hematocrits of AZT-treated mice and control mice.
      However, SCF and SCF-hemin combinations failed to raise hematocrits. Reticulocyte
      numbers were significantly consistently increased only in hemin-treated mice
      receiving AZT. The numbers of CFU-E were increased in bone marrow of AZT-treated
      mice receiving hemin. Therefore, SCF did not enhance the erythropoietic effect of
      hemin in AZT-treated immunodeficient mice.

PMID- 8856090
TI  - Biological and clinical significance of in vitro prednisolone resistance in adult
      acute lymphoblastic leukaemia.
AB  - It has been reported that in vitro prednisolone (PDN) resistance provides a
      prognostic value in childhood acute lymphoblastic leukaemia (ALL). This study
      aimed at investigating the biological and clinical significance of in vitro PDN
      resistance in adult ALL. Blast cells from 30 patients were exposed to PDN (0.1
      microM-35 microM) and cytotoxicity was determined by the soluble tetrazolium
      formazan 2,3-bis (2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino) carbamyl]-2H
      tetrazolium hydroxyde (XTT) colorimetric assay. The IC50 (defined as the drug
      concentration that results in 50% growth inhibition) varied greatly among the
      samples, from 0.3 microM to > 35 microM; 15 microM was subsequently chosen as
      IC50-cut-off point between in vitro resistant and sensitive cases. PDN-induced
      cytotoxicity was significantly related to apoptosis, as demonstrated by
      regression analysis; in sensitive cases, however, the percentage of apoptotic
      cells after in vitro PDN treatment was significantly increased compared with
      control (p = 0.002). Immunofluorescence evaluation of intracellular BCL-2 protein
      showed an equal percentage of positive cells in the two groups, but in resistant
      cells a higher mean fluorescence intensity (p = 0.04) was demonstrated. In vitro
      sensitive and resistant patients did not display differences in clinical
      characteristics, in cytological, karyotypic and immunophenotypic features and in
      the outcome of induction therapy. Disease-free survival (DFS), however, was
      significantly better in sensitive patients (p = 0.02).

PMID- 8856092
TI  - Quantitation of resistance to cytosine arabinoside by myeloid leukemic cells
      expressing bcl-2.
AB  - The presence of bcl-2 in myeloid leukemias has been associated with a decrease in
      therapy-induced apoptosis, reduced patient survival and in vitro autonomous
      growth of leukemic cells. The present study focuses on the quantitation of
      resistance to increasing doses of 1-beta-d-arabinofuranosylcytosine (Ara-C) by
      using hematological tumors expressing different levels of bcl-2. Scanning
      densitometry of Western blots demonstrated that the myeloid U-937 cells express
      low levels of bcl-2 (RD = 0.008), whereas the follicular lymphoma RL-7 expressed
      very high levels (RD = 3.084). Colony formation was also examined following
      incubation with Ara-C and RL-7 cells demonstrated a higher clonogenic survival
      (LD50 = 0.5 microns) when compared with U-937 cells (LD50 = 0.005 microM).
      Similarly, the level of bcl-2 expression in each cell line was also related to
      apoptosis with U-937 cells demonstrating increased DNA fragmentation when
      compared with RL-7 cells. To further evaluate the effect of upregulated bcl-2 on
      Ara-C treatment, U-937 cells were transfected with a retroviral vector carrying
      the murine bcl-2 or vector alone. Upregulation of bcl-2 by myeloid leukemic cells
      increased the resistance by 3 logs to Ara-C when comparing LD50 values from
      clonogenic assays, and decreased apoptosis by at least 3 logs when measuring dUTP
      positive cells by flow cytometry.

PMID- 8856091
TI  - Maintenance therapy with interferon-alpha (IFN-alpha) versus IFN-alpha plus
      chemotherapy in multiple myeloma (MM). The Greek Myeloma Study Group.
AB  - Results of studies using IFN-alpha treatment for maintaining remission and
      prolonging survival in multiple myeloma (MM) are in conflict and trials seeking
      optimum use for this biological response modifier are continuing. Between 1989
      and 1993 a prospective randomized multicentre trial was undertaken to evaluate
      the role of the combination of IFN-alpha with chemotherapy (CT) in maintenance
      treatment of MM. For remission induction, in patients 65 yr or younger, we used
      VAD (group A) and for the remaining Melphalan and Prednisone (MP) (group B). For
      maintenance, patients were randomized to receive IFN-alpha 3 x 10(6) i.u. s.c.
      t.i.w. (group I) or alternating monthly cycles of IFN-alpha and CT. The CT cycles
      were also alternated (VAD, MP, CP) in an effort to prevent the development of
      multidrug resistance. Median survival of the two maintenance groups from
      randomization (36 months for group I and 31 months for group II, p = 0.3) as well
      as response duration (13 months in group I and 15 months in group II, p = 0.95)
      were similar. Toxicities were more pronounced both with VAD induction and in the
      combination maintenance arm. The addition of chemotherapy to the IFN maintenance
      regimen in MM did not have an advantage over IFN alone.

PMID- 8856093
TI  - Serum procollagen III peptide concentration in iron overload.
AB  - Patients with severe iron overload may develop hepatic fibrosis due to iron
      toxicity. Unfortunately, the follow-up of the fibrogenic activity during
      treatment by histological examination of tissue biopsies carries potential side
      effects, and may therefore not be justified ethically. Recently, the serum
      concentration of procollagen type III peptide (S-PIIINP) has been shown to be a
      valid serum marker of the activity of collagen metabolism in conditions with
      hepatic fibrosis unrelated to iron overload. In order to evaluate the potential
      usefulness of this test in patients with fibrosis due to iron overload, we
      investigated the relationship between the PIIINP serum concentration and the size
      of iron overload in 18 patients with hereditary haemochromatosis (HH) and in 14
      patients with transfusional iron overload. A close correlation was found between
      S-ferritin and S-PIIINP (r = 0.73, p < 0.0001). Follow-up of 6 patients during
      iron depletion treatment revealed a normalization of the serum aminotransferase
      concentration before normalization of S-PIIINP was found. This may indicate that
      excess iron directly induces an increase in fibrogenesis rather than the
      increased fibrogenesis is secondary to hepatocellular injury caused by iron
      excess. Thus, serial measurements S-PIIINP may be useful in follow-up of the
      fibrogenic process due to iron overload.

PMID- 8856094
TI  - A long-term follow-up study of interferon treatment for chronic hepatitis C in
      Japanese patients with congenital bleeding disorders.
AB  - Twenty-one HIV negative Japanese patients with chronic hepatitis C who had
      congenital bleeding disorders, 15 hemophilia A, 3 hemophilia B, 1 von
      Willebrand's disease, 1 afibrinogenemia and 1 thrombasthenia, were treated with 9
      million units 3 times a week of natural interferon (IFN)-alpha for 6 months. They
      were followed, biochemically and virologically, for at least 18 months after
      therapy discontinuation to evaluate the long-term results. Liver biopsy,
      hepatitis C virus (HCV) genotyping and quantification of viral load by polymerase
      chain reaction (PCR) were performed to identify the predictors of a favorable
      response to IFN treatment. One male patient with hemophilia A dropped out because
      of general fatigue and was excluded from evaluation. Ten (50.0%) patients
      continued to be HCV RNA negative in serum together with normal ALT levels
      throughout the study. Subtype 1b and a high level of viremia significantly
      associated with an unfavorable outcome on the response to IFN although liver
      histology was not definitive for predicting the response. We concluded that a 6
      month treatment with high doses of natural IFN-alpha was effective in inducing a
      long-term response without relapse of viremia in 50% of chronic hepatitis C
      patients with congenital bleeding disorders and that HCV subtype and pretreatment
      level of viremia were useful predictors of the response to IFN in treating such
      patients.

PMID- 8856095
TI  - Effect of interferon-alpha on immunoglobulin production by peripheral blood
      mononuclear cells in multiple myeloma.
AB  - To test a hypothesis that interferon-alpha (IFN) treatment might restore normal
      immunoglobulin (Ig) production in multiple myeloma (MM), the effect of IFN on Ig
      isotype (IgG and IgA) production by peripheral blood (PB) and bone marrow (BM)
      mononuclear cells (MNCs) in MM patients was analyzed by ELISA. IFN at a
      concentration of 1000 U/ml was found to enhance IgA production by PB MNCs in IgA
      MM and had a trend to stimulate IgG production in IgG-MM. The effect of IFN on
      nonparaprotein Ig isotype production was more variable, with mostly neutral or
      inhibitory effects being seen in both the MM subtypes. In contrast to the
      influences observed in MM patients, IFN at the same concentration inhibited both
      IgG and IgA production by PB MNCs in healthy controls. In studying BM cells, IFN
      was found to reduce IgA production in IgA-MM, but had a neutral effect on IgG
      production in IgG-MM. In the controls, the production of both the IgG and the IgA
      isotypes by BM MNCs was decreased by IFN. On the basis of these results it seems
      that the disease itself somehow affects the Ig-producing cells in MM, when
      measured as different responses of the cells to exogenous IFN in vitro. The
      results do not support the hypothesis that IFN treatment could restore normal Ig
      production in MM patients.

PMID- 8856096
TI  - Recurrent mutation Asn45-->Ser of glycoprotein IX in Bernard-Soulier syndrome.

PMID- 8856097
TI  - CFU-GM are not increased in peripheral blood of patients with chronic lymphocytic
      leukaemia.

PMID- 8856098
TI  - A novel mutation in the beta-globin gene causing beta-thalassaemia in a Swedish
      family.

PMID- 8856099
TI  - Leucocyte and platelet derived bioactive substances in stored standard platelet
      concentrates.

PMID- 8856100
TI  - Sweet's syndrome associated with paracentric inversion of chromosome 3q in a
      patient with multiple myeloma.

PMID- 8856102
TI  - Cloning and sequence analysis of the dimethylsulfoxide reductase structural gene
      from Rhodobacter capsulatus.
AB  - The dimethylsulfoxide reductase structural gene (dorA) of Rhodobacter capsulatus
      was cloned from a lambda expression library. The nucleotide sequence of the dorA
      gene was determined and it was found to encode a protein of 825 amino acids.
      Comparison of the deduced amino-acid sequence of DorA with N-terminal sequence of
      purified dimethylsulfoxide reductase from Rhodobacter capsulatus showed that the
      pre-protein possesses a 41-amino-acid N-terminal signal polypeptide. All of the
      conserved segments which have been described in bacterial enzymes which bind
      molybdopterin guanine dinucleotide (Berks, B.C., Ferguson, S.J., Moir, J.W.B. and
      Richardson, D.J. (1995) Biochim, Biophys. Acta 1232, 97-173) were identified in
      Rhodobacter capsulatus dimethylsulfoxide reductase.

PMID- 8856103
TI  - Effect of polyunsaturated fatty acids deficiency on oxidative phosphorylation in
      rat liver mitochondria.
AB  - Liver mitochondria isolated from controls or polyunsaturated fatty acid (PUFA)
      deficient rats were studied for oxidative phosphorylation. A PUFA-deficient diet
      led to a dramatic change in the fatty acid composition of mitochondrial lipid
      content, similar to that reported in the literature. Besides the changes in lipid
      composition, mitochondrial volume was enlarged (+45% in state 4 and two-fold in
      state 3). State 4 respiration was increased together with a decrease in
      protonmotive force. The non-ohmicity of the relationship between non
      phosphorylating respiration and protonmotive force was more pronounced in the
      PUFA-deficient group. State 3 oxygen consumption as well as the rate of ATP
      synthesis showed no difference between the two groups, whereas the protonmotive
      force decreased substantially in mitochondria from PUFA-deficient animals. In
      contrast, ATP/O ratios were decreased in the PUFA-deficient group when determined
      at subsaturating ADP concentration. Taken together, these results are in
      agreement with both an increased non-ohmic proton leak and an increased redox
      slipping. The relative importance of these two effects on the overall efficiency
      of oxidative phosphorylation depends on both the rate of oxidative
      phosphorylation and the maintained protonmotive force. Hence, in isolated
      mitochondria the respective role of each effect may vary between state 4 and
      state 3.

PMID- 8856104
TI  - Manganese as a cosubstrate for the phosphorylation of the sarcoplasmic reticulum
      Ca-dependent adenosine triphosphatase with orthophosphate.
AB  - The phosphorylation of the sarcoplasmic reticulum Ca-ATPase (EC 3.6.1.38) with
      P(i) was characterized using Mn as a Mg analogue. Steady state and transient
      fluorescence and radioisotopic techniques were used; the affinities of Mn and
      P(i) for the enzyme and the rate constants of the phosphorylation and
      dephosphorylation reactions were determined, under several conditions. The
      reactions were carried out at pH 5.5 to minimize the binding of contaminant Ca to
      the transport sites, thus avoiding the use of Ca chelators. The apparent affinity
      of Mn binding at low [Mn] is larger in the absence of P(i) (35 microM) than in
      the presence of saturating P(i) (70 microM). On the contrary, the apparent
      affinity of Mn for the formation of the phosphoenzyme increases, from 1.5 mM to
      0.15 mM, upon increasing [P(i)] in the millimolar range. The apparent affinty of
      P(i) for the formation of the phosphoenzyme also increases, from 2.2 mM to 0.2
      mM, upon increasing [Mn] in the millimolar range. The equilibrium of the
      phosphoenzyme with the noncovalent Mn.P(i). Enzyme complex favors the covalent
      species. The simulation of a reaction model including the random binding of 2 Mn
      and I P(i) per mol of ATPase and a noncovalent complex in equilibrium with the
      phosphoenzyme, using a set of equilibrium constants deduced from the results,
      agree with the experimental data.

PMID- 8856105
TI  - Structural factors of rotenone required for inhibition of various NADH-ubiquinone
      oxidoreductases.
AB  - We performed a structure-activity study of a series of synthetic rotenone
      analogues to elucidate the structural factors of rotenone required for inhibition
      and to probe the structural properties of the rotenone binding site of various
      NADH-ubiquinone oxidoreductases (NDH), including both proton-pumping (NDH-1) and
      non-proton-pumping (NDH-2) enzymes, from bovine heart mitochondria, potato tuber
      (Solanum tuberosum L.) mitochondria and Escherichia coli (GR 19N) plasma
      membranes. Using a benzyloxy group as a substitute for the E-ring moiety of
      natural rotenone, systematically selected structural modifications of the A-ring
      became feasible. The inhibitory potency of bovine NDH markedly varied depending
      upon structural modifications of the A-ring. The native chemical structure (2,3
      dimethoxy substitution) appeared to be the most favorable for the activity. The
      spatial location of the hydrogen-bond acceptable methoxy oxygens may be important
      for tight fitting into the binding site. However, replacing one of the two
      methoxy groups by an ethoxy group almost completely retained the activity,
      indicating that the binding environment of the A-ring moiety is spacious enough
      to accommodate a substituent larger than the methoxy group. The manner of action
      of the derivative lacking the 12-C = O group in the C-ring differed from that of
      natural rotenone, indicating that this functional group is important for
      supporting the inhibitory action of natural rotenone itself. Regarding potato
      tube and E. coli NDH-1, the sensitivity of the two enzymes to the inhibition by
      rotenone analogues was much lower than that of the bovine enzyme. The 2,3
      dimethoxy substitution was the most favorable for the activity with potato NDH-1,
      whereas this substitution pattern was not necessarily the best with E. coli NDH
      1. A rule governing inhibitory potency depending upon structural modifications
      was ambiguous for the two enzymes because of a small variation in the inhibitory
      potencies. These findings indicated that the local binding environment of the A
      ring moiety of rotenone in bovine NDH is specific and differs considerably from
      that in potato and E. coli NDH-1.

PMID- 8856106
TI  - Some characteristics of cytochrome f in the cyanobacterium Phormidium laminosum:
      its sequence and charge properties in the reaction with plastocyanin.
AB  - Part of the petCA operon was cloned and the sequence of the cytochrome f gene
      from the moderately thermophilic cyanobacterium Phormidium laminosum determined.
      A partial sequence of the petC gene encoding the Rieske iron-sulphur protein was
      also obtained. The cytochrome f gene encodes a mature protein of 385 residues and
      a leader sequence of 45 residues. The mature protein contains several acidic or
      neutral residues corresponding to basic residues in the turnip protein. Some of
      the latter are thought to be important for the interaction with plastocyanin via
      its "eastern' face. Many of the corresponding residues on the eastern face of P.
      laminosum plastocyanin are either basic or neutral instead of acidic. These
      comparisons suggested that the local charges on P. laminosum cytochrome f that
      are important for its interaction with the homologous plastocyanin may be
      negative rather than positive. The importance of acidic groups was confirmed by
      measuring the rates of reduction of horse heart cytochrome c and P. laminosum and
      spinach plastocyanins by the cytochrome bf complex isolated from P. laminosum. P.
      laminosum plastocyanin gave the highest rates, which decreased at high ionic
      strength, confirming the importance of positive local charges on this protein.
      When extrapolated to infinite ionic strength the rates observed with the two
      kinds of plastocyanin were similar, but cytochrome c became unreactive. An
      optimum was observed in the ionic strength response with P. laminosum
      plastocyanin.

PMID- 8856107
TI  - The agonist selectivity of a mouse B1 bradykinin receptor differs from human and
      rabbit B1 receptors.
AB  - A genomic clone encoding the mouse B1 receptor was isolated by homology to the
      human B1 receptor cDNA. The deduced amino acid sequence of the mouse B1 receptor
      is 72% identical to the human B1 receptor and 73% identical to the rabbit B1
      receptor. Ligand binding studies of the mouse B1 receptor expressed in COS cells
      indicate that it has the pharmacological properties associated with the B1
      receptor subtype. However the pharmacology of the mouse receptor is unique in
      that it possesses a 2-3-fold selectivity for the 'classical' B1 agonist des
      Arg9BK over the agonist des-Arg10 kallidin. In contrast, the human and rabbit B1
      receptors exhibit an approx. 2000- and 150-fold selectivity, respectively, for
      des-Arg10kallidin over des-Arg9BK. Thus relative to the human and rabbit B1
      receptors the mouse B1 receptor has the opposite selectivity for kinin agonists.
      The DNA sequence of the region encoding bradykinin was determined for two
      different mouse kininogen cDNA clones, both encode the sequence Arg-BK.
      Antipeptide antibodies directed against a C-terminal peptide of the human B1
      receptor were produced. Initial characterization of this antibody indicates that
      it detects specific bands by Western blot analyses that are present in membranes
      prepared from COS cells transfected with the human B1 receptor cDNA but not from
      mock transfected COS cells.

PMID- 8856108
TI  - Human lung fibroblasts express multiple means for enhanced activity of bradykinin
      receptor pathways.
AB  - Human lung fibroblasts represent important targets for the biologic activities of
      bradykinin (BK). We have identified multiple mechanisms in these cells which may
      extend their potential for BK receptor responsiveness, particularly with regard
      to generation of arachidonate metabolites. These fibroblasts can constitutively
      express B2 and B1 BK receptors concurrently, both coupled to the pathway for
      arachidonate metabolism resulting in generation of PGE2 and the potent vasoactive
      lipid mediator Thromboxane A2. Although expression patterns for B2 and B1
      receptors have classically been regarded as 'constitutive' and 'inducible',
      respectively, we demonstrate that in human lung fibroblasts both can be expressed
      spontaneously at equivalent biologic activity levels without selective induction
      by other mediators. Concurrent B2/B1 receptor expression extends the scope of
      fibroblast response potential to both BK and des-Arg9-BK in the same time frame.
      We have identified additional short-term and long-term cellular events, involving
      both protein kinase pathways through which BK receptors act and those which act
      upon BK receptors, that result in enhanced BK receptor response potential. These
      properties of BK receptors may affect whether fibroblast behaviors maintain
      controlled activities of normal homeostasis or foster escalating cellular
      responses which may influence the progression of certain human disease states.

PMID- 8856109
TI  - Interaction between growth factors and kinins in arterial smooth muscle cells.
AB  - Bradykinin receptors are present on vascular smooth muscle cells; however, the
      regulation and biological function of these receptors is unclear. To address
      these questions the interaction between growth factors and kinins in cultured
      arterial smooth muscle cells has been examined. Based upon the data a hypothesis
      is presented that platelet-derived growth factor (PDGF) upregulates cell surface
      bradykinin B2 receptors on arterial smooth muscle cells. The biological effect of
      the increase in B2 receptors is currently unclear but under certain conditions
      they may enhance mitogenesis. These mitogenic effects however, are strongly
      opposed by the effects of bradykinin acting via a B1-type of receptor which
      mediates potent inhibition of growth factor-induced mitogenesis.

PMID- 8856110
TI  - Receptors for kinins: from classical pharmacology to molecular biology.
AB  - In the past twenty years, we have focused our efforts on the study of kinin
      receptors involved in contraction or relaxation of vascular smooth muscle.
      Initial studies on rabbit vessels led to the discovery of two kinin receptors, B1
      and B2, mediating contraction of the rabbit aorta (B1) and the rabbit jugular
      vein (B2). Studies on dog vessels contributed to the identification of B2
      receptors in arterial endothelium promoting the release of NO and the relaxation
      of arterial smooth muscles; further studies on dog renal vessels led to the
      demonstration of B2 receptors in endothelia and in the smooth muscle, mediating
      relaxation through NO (endothelia) and prostanoids (smooth muscle). B1 receptors
      that relax renal arterial smooth muscle through the release of prostanoids were
      also identified. In other vessels, B2 receptors may also mediate smooth muscle
      contraction. Recent studies in human vessels (umbilical vein) have confirmed the
      existence of contractile B1 and B2 receptors in venous smooth muscles. B1 and B2
      receptors have been cloned; molecular biology has provided the reference data for
      comparison with findings of classical pharmacology and binding assays.
      Similarities and differences in B1 and B2 receptors between human and animal
      tissues demonstrate the heterogeneity (related to species) of kinin B2 and B1
      receptors and confirm the findings of early classical pharmacological
      experiments.

PMID- 8856111
TI  - Polymorphisms in the gene for the human B2-bradykinin receptor. New tools in
      assessing a genetic risk for bradykinin-associated diseases.
AB  - The B2-bradykinin receptor gene has been proposed as one of the candidate genes
      involved in the complex genetic underpinnings of common chronic disorders such as
      hypertension, ischemic heart disease or allergic asthma. Suitable genetic markers
      are needed to study these hypotheses. Therefore, it was our aim to identify
      polymorphic sites in the B2-receptor gene. Up to now, we characterized four
      polymorphisms: one in the promoter region and three other ones in each of the
      exons. Possible biological consequences are delineated and preliminary results of
      allele specific different biological action are shown.

PMID- 8856112
TI  - Transcriptional regulatory elements in the rat bradykinin B2 receptor gene.
AB  - In an attempt to elucidate the mechanisms underlying the regulation of bradykinin
      B2 receptor gene expression, the molecular structure of the rat gene including
      the 5'-flanking region was characterized (J. Biol. Chem. 269: 26920-26925, 1994).
      In this study we show that the gene spans about 32 kb, including a long first
      intron of 25 kb. The promoter region drives reporter gene expression in NG108-15
      neuroglioma cells, and its expression is upregulated by cAMP, bradykinin, phorbol
      esters and by coexpression of an activated ras oncogene but not by dexamethasone.

PMID- 8856113
TI  - On the structure of the amino-terminal domain ED1 of the B2 receptor.

PMID- 8856114
TI  - Endothelium-derived hyperpolarizing factor: a key mediator of the vasodilator
      action of bradykinin.
AB  - Bradykinin causes vasodilatation by stimulating the production of vasodilator
      prostanoids and nitric oxide (NO). However, there is an additional component that
      is mediated by a diffusible endothelium-derived hyperpolarizing factor (EDHF).
      The non-selective inhibitor of arachidonic acid metabolism eicosatetraynoic acid
      inhibits the EDHF-mediated component of the relaxation to bradykinin. Therefore,
      EDHF may be an archidonic acid metabolite. The diffusible nature of EDHF has been
      disputed because of the inability to consistently detect the factor using
      perfusion bioassay techniques. However, administration of the acyltransferase
      inhibitor thimerosal facilitates the release of EDHF by endothelial cells in
      culture. Further studies are warranted to identify EDHF and explore further its
      functions in vasomotion.

PMID- 8856115
TI  - A new generation of bradykinin antagonists.
AB  - Bradykinin B2 receptors are constitutively expressed, and require the entire
      peptide chain of bradykinin for recognition. Expression of B1 receptors is
      induced in inflammation; they recognize BK-(1-8). Heretofore blockade of all the
      actions of bradykinin required two different antagonists, one for each class of
      receptors. The new antagonists described here are full chain antagonists having
      high potency on B2 receptors, but they are also very potent antagonists for B1
      receptors. They are highly resistant to kininases and show very long action in
      vivo. These antagonists contain the novel amino acid alpha-(2-indanyl)glycine
      (IgI) at positions 5 and 7. The peptide DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg
      (designated B9430) shows all these desirable characteristics. It represents a new
      class of bradykinin antagonist peptides.

PMID- 8856116
TI  - Novel bradykinin receptor antagonists from a structurally directed non-peptide
      combinatorial library.

PMID- 8856117
TI  - 'Targeted' molecular diversity: design and development of non-peptide antagonists
      for cholecystokinin and tachykinin receptors.
AB  - A drug design strategy to non-peptide small molecule antagonists of neuropeptides
      is described that targets the molecular diversity which exists in the
      'privileged' data set of the physico-chemical properties represented by the side
      chains of the 20 genetically encoded amino acids. The strategy is exemplified by
      the design of a selective and high affinity cholecystokinin CCK-A antagonist PD
      140548, CCK-B antagonist CI-988 (formerly PD 134308) tachykinin NK-1 antagonist
      PD 154075 and NK-2 antagonist Cam-2291. The NK-3 antagonists, PD 157672 and the
      non-peptide PD 161182, were developed from an information-rich dipeptide library
      constructed from 256 N-protected dipeptides and 64 hydrophobic biased dipeptides.

PMID- 8856118
TI  - A new type of bradykinin B2 receptor antagonists: bradykinin analogs with N-alkyl
      amino acids at position 2.
AB  - It is commonly assumed that bradykinin B2 receptor antagonists bind to a receptor
      site partially different from that for agonists. Thus, it is likely that there
      exists more than one key modification to convert bradykinin receptor agonists
      into antagonists. In this respect, [L-NMePhe2]-BK represents the basic structure
      of a new type of bradykinin B2 receptor antagonists without any replacement at
      position 7. This compound inhibits both in vitro bradykinin-induced contraction
      of the guinea pig lung strip and in vivo bradykinin-induced bronchoconstriction.
      Furthermore, this analog shows analgesic activity, blocks in a dose-dependent
      manner the bradykinin-induced Ca2+ release from macrophages and inhibits at a
      concentration of 10(-13) M the bradykinin-induced cytokine release from
      mononuclear cells. Combinations with structural modifications previously
      performed for other B2 receptor antagonists rather reduce than enhance the
      potency.

PMID- 8856119
TI  - Effect of combined B1 and B2 kinin receptor blockade in porcine endotoxin shock.
AB  - In order to investigate the contribution of kinin receptor antagonism in the
      treatment of LPS-induced shock we conducted a randomized study with anaesthetized
      piglets. Before randomization the animals were stratified according to
      predetermined health criteria under baseline conditions. One group of control
      animals received LPS from S. abortus equi (2 micrograms/kg/h i.v. for 8 h) and
      saline (Group 1). Another group received LPS and the B2 antagonist CP-0127 (3
      micrograms/kg/min), beginning 1 h after LPS (Group 2). Group 3 received LPS and
      the B2 antagonist in the aforementioned doses, and the B1 antagonist Leu9-des
      Arg10-kallidin (3 micrograms/kg/min), also beginning 1 h after LPS. Overall
      survival figures after 8 h of LPS infusion were: Group 1, 10/22 (45%); Group 2,
      10/17 (59%); Group 3, 10/28 (36%). Fifty percent (29/58) of animals that were
      healthy at baseline survived, but only 11% (1/9) of sick animals survived (Log
      Rank p = 0.0001). In the subset of healthy animals, survival rates for Groups 2
      and 3 were 77% and 38%, respectively (p = 0.0519). It appears, therefore, that B2
      blockade attenuates LPS-induced mortality whereas additional B1 blockade seems to
      reverse these beneficial effects. This suggests that in this animal model the B1
      receptor does not serve the same purpose as the B2 receptor, and that up
      regulation of B1 receptors during LPS shock may be an important mechanism of host
      defence.

PMID- 8856120
TI  - Rat bradykinin B2 receptor: immunochemical characterization and
      immunovizualization in epithelial and smooth muscle cells.

PMID- 8856121
TI  - Exon 1 sequence of the human B2 bradykinin receptor gene and its transcript.

PMID- 8856123
TI  - Autoradiographic visualization of B1 bradykinin receptors in porcine vascular
      tissues in the presence or absence of inflammation.
AB  - B1 bradykinin receptors were visualized by using the B1 bradykinin receptor
      agonist [3H]des-Arg10-kallidin in receptor autoradiography experiments.
      Cryosections were prepared from arterial vessels from a healthy control pig, a
      pig with pre-existing inflammation and an animal with experimental sepsis induced
      by an infusion of bacterial lipopolysaccharide (LPS). Only diffusely scattered
      silver grains with no preference for a distinct tissue structure were detected on
      emulsion-coated coverslips above the cryosections from the healthy control
      animal. This indicates that under normal circumstances no or only minute amounts
      of B1 bradykinin receptors are present in these tissues. In contrast, a 3-fold
      increase in specific B1 bradykinin receptor binding was observed on both the
      corresponding preparations of the sick piglet and of that with experimentally
      induced sepsis. A similar enhancement of specific [3H]des-Arg10-kallidin binding
      occurred in preparations devoid of endothelium. By comparison with the stained
      cryosection on the slide the silver grains showed a preferential distribution
      above smooth muscle cells. Taken together our data are consistent with the
      hypothesis that B1 bradykinin receptors are induced in the muscle layer of large
      vessels not only after experimentally-induced sepsis but also in pre-existing
      inflammatory disease.

PMID- 8856122
TI  - Potentiation of the biological efficacy of bradykinin by ACE inhibitors: a shift
      in the affinity of the B2 receptor?
AB  - We have recently demonstrated that the angiotensin I-converting enzyme (ACE)
      inhibitor ramiprilat augments the endothelium-dependent dilator response to
      bradykinin in the isolated perfused rat heart by an interaction at the B2
      receptor level. We have now investigated whether this is an effect of the ACE
      inhibitor class of compounds by studying the bradykinin-induced vasoconstriction
      in isolated segments of the rabbit jugular vein. Among five different ACE
      inhibitors, moexiprilat and ramiprilat proved to be the most effective in
      potentiating the constrictor response to bradykinin. This effect was not mimicked
      by other protease inhibitors or the synthetic ACE substrate hippuryl-L-histidyl-L
      leucine. The ACE inhibitors, on the other hand, failed to affect the constrictor
      or dilator responses elicited by other receptor-dependent agonists in this
      vascular model. These findings demonstrate that ACE inhibitors selectively
      potentiate the B2 receptor-mediated constrictor response to bradykinin in the
      rabbit jugular vein, possibly by increasing the affinity of the B2 receptor.

PMID- 8856124
TI  - Induction of a B1-receptor mediating hypotensive response in young brown Norway
      rats.
AB  - A hypotensive response to intravenously injected des-Arg9-bradykinin was elicited
      in young male Brown Norway rats (8-12 weeks-old), when the rats were
      intravenously injected with endotoxin (30 micrograms/kg) 24 h before they were
      repeatedly injected with bradykinin or des-Arg9-bradykinin. The potency of this
      inducible dose-dependent hypotensive response to des-Arg9-bradykinin was
      comparable to that induced by bradykinin on a molar base (3-30 nmol/kg). A
      hypotensive response to des-Arg9-bradykinin could also be induced when the rats
      were pretreated with endotoxin 6 h before. However, the potency of the response
      was less than that induced by 24-h pretreatment. This inducible response to des
      Arg9-bradykinin did not occur in old rats (8-10 months old). Intravenous infusion
      of a B1-receptor antagonist, des-Arg9-[Leu8]-bradykinin, suppressed the
      hypotensive response of des-Arg9-bradykinin. These results suggest that the B1
      receptor, mediating hypotension in rats, was inducible through time-dependent and
      age-dependent sensitization by endotoxin pretreatment.

PMID- 8856125
TI  - Visualisation of bradykinin B2 receptors on human brain neurons.

PMID- 8856126
TI  - Localization of bradykinin B2 receptors in sheep uterus.
AB  - The localization and characterization of bradykinin B2 receptors in sheep uterus
      was carried out using a radiolabelled B2 receptor ligand, 3,4
      hydroxyphenypropionyl-D-Arg0-[Hyp3,Thi5,D-++ +Tic7,D-Oic8] bradykinin (HPP
      HOE140). Competition of the radioligand, [125I]HPP-HOE140, from membrane
      preparations of anoestrus sheep uterus by bradykinin agonists and antagonists
      revealed the presence of high- and low-affinity binding sites with ligand
      specificity typical of the bradykinin B2 receptor. Using in vitro autoradiography
      on tissue sections, intense binding was visible over the superficial epithelial
      layer of the endometrium and inner third of the myometrium of anoestrus sheep
      uterus. Bradykinin B2 receptors in the myometrium were down regulated in pregnant
      sheep uterus. We demonstrate that binding studies using [125I]HPP-HOE140 offer
      high sensitivity and specificity for characterization, quantitation and
      localization of the bradykinin B2 receptors in tissues and offers new information
      on uterine bradykinin B2 receptors.

PMID- 8856127
TI  - Inducible bradykinin B1 receptor in isolated human ileum.

PMID- 8856128
TI  - Receptors for kinins: from classical pharmacology to molecular biology.
AB  - In the past 20 years, we have focused our efforts on the study of kinin receptors
      involved in contraction or relaxation of vascular smooth muscle. Initial studies
      on rabbit vessels led to the discovery of two kinin receptors, B1 and B2,
      mediating contraction of the rabbit aorta (B1) and the rabbit jugular vein (B2).
      Studies on dog vessels contributed to the identification of B2 receptors in
      arterial endothelium promoting the release of NO and the relaxation of arterial
      smooth muscles; further studies on dog renal vessels led to the demonstration of
      B2 receptors in endothelia and in the smooth muscle, mediating relaxation through
      NO (endothelia) and prostanoids (smooth muscle). B1 receptors that relax renal
      arterial smooth muscle through the release of prostanoids were also identified.
      In other vessels, B2 receptors may also mediate smooth muscle contraction. Recent
      studies in human vessels (umbilical vein) have confirmed the existence of
      contractile B1 and B2 receptors in venous smooth muscles. B1 and B2 receptors
      have been cloned; molecular biology has provided the reference data for
      comparison with findings of classical pharmacology and binding assays.
      Similarities and differences in B1 and B2 receptors between human and animal
      tissues demonstrate the heterogeneity (related to species) of kinin B2 and B1
      receptors and confirm the findings of early classical pharmacological
      experiments.

PMID- 8856129
TI  - Investigation into the role of cyclooxygenase products in the bradykinin response
      on isolated human myometrium and umbilical artery.
AB  - The aim of this study was to investigate the response to bradykinin (BK) on human
      myometrium and umbilical artery with respect to cyclo-oxygenase (CO) products.
      Dose/concentration response curves to BK were performed +/-2.79 microM
      indomethacin. On human myometrium the response to BK (0.001-50 nmol) was biphasic
      and consisted of a dose-related increase in myometrial tension which was followed
      by a period of inhibition of myogenic activity. In tissues from P donors the
      presence of indomethacin had no significant effect on the excitatory response,
      but the inhibitory component of the response was reduced. In tissues from NP
      donors indomethacin significantly enhanced the BK effect at higher doses and the
      inhibitory component of the response was reduced. On the HUA cumulative addition
      of BK (1-1000 nM) resulted in dose dependent constriction with desensitisation at
      the highest dose (EC50 = 38 nM). The presence of indomethacin had no significant
      effect on BK response on HUA. These findings suggest that CO products contribute
      significantly to response to BK on the human myometrium but not on HUA and that
      different CO products are produced by P and NP tissue.

PMID- 8856130
TI  - Comparison of the effects of bradykinin and related compounds on isolated mouse
      and human uterus.
AB  - The purpose of this study was to investigate and compare the response of the
      isolated human myometrium (non-pregnant donors) and mouse uterus to bradykinin
      (BK), Lys-BK and des-Arg9-BK (+/-2.79 microM indomethacin). The uterine strips
      were set up for superfusion using Kerbs' solution. On the human myometrium the
      responses to BK and Lys-BK were biphasic and consisted of an increase in
      myometrial tension which was followed by a period of inhibition of myogenic
      activity. Des-Arg9-BK evoked a monophasic contractile response. On the mouse
      uterus the responses to BK, Lys-BK and des-Arg9-BK were monophasic and
      contractile only. On both of the tissues the contractile responses to BK and Lys
      BK were bell shaped and indomethacin abolished the bell-shaped part of the dose
      response curves. The response to des-Arg9-BK and the inhibitory response to BK
      and Lys-BK, on the human tissue, was also significantly reduced in the presence
      of indomethacin. The results of this study suggest that the human and mouse
      uterus do posses kinin receptors of the B2 type but on human myometrium these are
      biphasic responses.

PMID- 8856131
TI  - A preliminary study of prostaglandin release by bradykinin (BK) on isolated human
      myometrium.
AB  - The aim of this study was to investigate whether the response to BK on isolated
      human myometrium from non-pregnant (NP) and pregnant (P) donors involves the
      release of prostaglandin I2 (PGI2) and/or of PGE2. BK was injected as a bolus
      dose into the flow of the superfusate. The perfusate was collected during a
      response to BK and PG concentration measured by enzymoimmunoassay for PGE2 or
      PGI2. The BK response was biphasic, consisting of contraction followed by
      inhibition of myogenic activity. In tissues from both NP and P donors BK was
      found to cause a dose related release of PGE2 and PGI2. BK evoked PGE2 release
      which was greater during the contractile response than in the inhibitory
      response. Following the same dose of BK, PGI2 release was found to be greater in
      the inhibitory response than in the contractile phase. The findings indicate that
      in isolated human myometrium the response to BK does involve the release of PGE2
      and PGI2 and in both NP and P tissue PGE2 release is greater in the contractile
      response phase whilst PGI2 predominates the inhibitory phase.

PMID- 8856132
TI  - Evidence for the promoting role of the intra-uterine kinin release in the
      development of late hypertonic saline-induced abortion.
AB  - Blood plasma kininogen (K), kininases (KS), kallikrein (KK), prekallikrein (PKK),
      and PGF2a were estimated in the common circulation of pregnant women during late
      saline-induced abortion and also in retroplacental blood after foetus delivery.
      The results provide evidence for intra-uterine kinin release from circulating
      blood K by locally activated KK from the very beginning of abortion. The greatest
      kinin release coincided with the strongest KS activity decrease at the time of
      foetus delivery. The pre-abortive KS levels correlated directly with abortus
      duration. Uterine PG biosynthesis was activated, but appeared to be a secondary
      process.

PMID- 8856133
TI  - Kinin-induced stimulation of bovine sperm motility and its relation to seminal
      plasma tissue kallikrein.

PMID- 8856134
TI  - Effect of protein C inhibitor (PCI) on in vitro fertilization.

PMID- 8856135
TI  - Effect of acute volume expansion associated with salt load on the profile of
      plasma angiotensins in rats.
AB  - We measured the changes produced in renin and the peptide components of the
      circulating renin-angiotensin system by acute volume expansion alone or
      associated with salt load in rats. With both maneuvers, there was a decrease of
      plasma renin activity (PRA) and plasma angiotensin (Ang) concentrations, but the
      changes were more pronounced in the salt-load group. In contrasting to Ang I and
      Ang II, plasma Ang-(1-7) concentration decreased significantly only within 60 min
      of 5.0% NaCl infusion (19.5 +/- 2.9 vs 30.5 +/- 1.9 pg/ml in the control group).
      As expected, plasma vasopressin increased markedly in the animals submitted to
      acute salt load (144.0 +/- 42.0 vs 5.0 +/- 0.2 pg/ml in the control group). The
      dissociation between the changes in plasma Ang-(1-7) and that of other plasma
      angiotensins is consistent with our previous studies using chronic salt load, and
      suggests that during acute volume expansion associated with salt load Ang I is
      preferentially converted to Ang-(1-7). In contrast to vasopressin, however,
      plasma Ang-(1-7) concentration increased only after chronic salt load, suggesting
      that this angiotensin may be more involved with long-term mechanisms of control
      of hydromineral balance.

PMID- 8856136
TI  - Cellular distribution and fate of the bradykinin antagonist HOE 140 in the rat
      kidney. Colocalization with the bradykinin B2 receptor.

PMID- 8856137
TI  - Cellular localization of bradykinin B1 receptor mRNA in the human kidney.
AB  - Cellular localization of the B1 receptor mRNA in the human kidney was identified
      by in situ hybridization histochemistry using digoxigenin-labeled riboprobe. With
      the antisense riboprobe, the B1 receptor mRNA was found mostly in the parietal
      layer of Bowman's capsule and the thin segment of Henle's loop. The renal
      carcinoma cells were stained with the B1 receptor riboprobe. These results showed
      the cellular localization of human renal B1 receptor mRNA and revealed sites of
      bradykinin action in regulating renal function under normal and pathological
      conditions.

PMID- 8856138
TI  - The status of B2 receptors in acute renal transplant rejection.

PMID- 8856139
TI  - Functional role of atrial natriuretic peptide in acute renal transplant
      rejection.

PMID- 8856140
TI  - The B2 receptor on cultured human decidua cells: release of arachidonic acid by
      bradykinin.
AB  - In vitro studies on cultured human decidual cells present evidence for the
      expression of the bradykinin B2 receptor. This protein was localized by
      immunocytochemical methods at the cellular plasma membrane and the mRNA was found
      in cellular extracts by RT-PCR. As a biological effect the release of 14C-AA was
      observed. Cells that had been incubated for 24 h with 14C-AA showed a bradykinin
      (BK)-induced release of radioactivity into the culture medium. This response was
      prevented by the specific bradykinin B2 receptor antagonist HOE 140. Pretreatment
      with LPS resulted in an increase of the spontaneous release of radioactivity.
      Adding BK, a further release of about 40-50% was to be shown. We conclude that BK
      can play a role in the case of bacterial infection of the fetal membranes AND may
      stimulate labour by an augmented production of prostaglandins.

PMID- 8856141
TI  - The effect of bradykinin and substance P on the arachidonate cascade of
      platelets.
AB  - Several peptide receptors are expressed on the surface of platelets, including B1
      and NK1, through which Bk and SP might influence platelet functions including
      their arachidonate cascade. The metabolites of the arachidonate cascade might
      play a regulatory role in the inter- and intracellular functions of platelets.
      Platelets were separated from fresh rat blood by differential centrifugation.
      Platelets (10(8) ml-1 in each sample) were preincubated with Bk or SP. The
      arachidonate cascade was investigated with [1-14C]arachidonic acid, as tracer
      substrate. The synthesised [14C]eicosanoids were isolated and quantitatively
      determined. Bradykinin elicited a biphasic dose-response curve in the formation
      of the vasoconstrictor and platelet aggregating thromboxane A2 (TxA2). Bk both
      inhibited (10(-8) mol/l), and elevated (10(-6) mol/l) the synthesis of TxA2 in
      the thrombocytes. The 12-HETE synthesis was inhibited by Bk (10(-8), 10(-7), 10(
      5) mol/l); 12-HETE is an endogenous regulator of prostacyclin synthesis. The
      formation of 12-HETE in platelets was stimulated by SP (10(-11), 10(-9), 10(-8)
      mol/l). The synthesis of TxA2 in platelets was either attenuated (10(-12) mol/l),
      or stimulated (10(-9) mol/l) by SP. According to our observations Bk and SP might
      play a regulatory role in the activation or deactivation of platelets.

PMID- 8856142
TI  - RT-PCR microlocalization of bradykinin B2 receptor mRNA in microdissected rat
      nephron segments.
AB  - Microlocalization of mRNA coding for the bradykinin 2 (BK2) receptor was carried
      out in the rat kidney. We combined reverse transcription and polymerase chain
      reaction (RT-PCR) with microdissection of individual renal tubule segments.
      Relative quantitation of the resulting amplified cDNA utilized densitometry of
      autoradiograms from Southern blots probed with a specific 32P labeled probe. The
      largest signals for BK2 receptor PCR product were detected in the cortical
      collecting tubule (CCT) and the proximal straight tubule (PST). BK2 receptor mRNA
      expression was also detected in the glomerulus, inner medullary thin limb (IMTL)
      and in the distal tubule (DT). Small but detectable signals were founded in the
      medullary thick ascending limb (MTAL). This distribution is consistent with
      multiple sites of BK action to account for different renal effects such as
      hemodynamics, water and electrolytic balance regulations.

PMID- 8856143
TI  - A new class of bradykinin antagonists containing indanylglycine.

PMID- 8856144
TI  - A new class of potent bradykinin antagonist dimers.

PMID- 8856145
TI  - New bradykinin antagonists having very high potency at B1 receptors.

PMID- 8856146
TI  - Comparative profile of novel potent bradykinin antagonists at human B1 and B2
      receptors.
AB  - We have undertaken a comparative pharmacological profile of novel bradykinin
      antagonists on human B1 and B2 receptor binding and functional assays. We found
      that there was an excellent correlation between binding and functional data for
      the compounds at the B1 receptor. In general, although there was a good
      correlation between the binding and functional data at the B2 receptor there was
      a greater degree of scatter in the correlation, particularly with compounds that
      possessed both B1 and B2 binding and antagonist activity. Of the compounds that
      were highly selective for the B2 receptor, CP-0597 had high binding activity but
      showed an unexpectedly low functional potency in the human ileum. The reason for
      this discrepancy is unclear. In general we found that binding activity with both
      the B1 and B2 antagonist compounds correlated well with their functional
      activity.

PMID- 8856147
TI  - In vivo pharmacological profile of novel, potent, stable BK antagonists at B1 and
      B2 receptors.

PMID- 8856148
TI  - Hybrid peptides having mixed substance P (NK1), neurokinin A (NK2) and bradykinin
      (BK2) antagonist properties.

PMID- 8856149
TI  - An NMR, CD, molecular dynamics and fluorometric study of the conformation of
      bradykinin antagonists B9340, B9430, B9436 and B9452 in water and in aqueous
      micellar solutions.

PMID- 8856150
TI  - Novel bradykinin antagonist dimers for the treatment of human lung cancers.

PMID- 8856151
TI  - Dissociation of blood-brain barrier permeability and the hypotensive effects of
      the bradykinin B2 agonist, RMP-7.

PMID- 8856152
TI  - Kinins in the cardiovascular system.
AB  - Growing evidence points to the existence of the components of the kallikrein
      kinin-system (KKS) in cardiac and vascular tissue forming systemic and local KKS
      pathways involving different cell types like endothelial cells, cardiomyocytes
      and vascular smooth muscle cells. Kinins may contribute to the regulation of the
      cardiovascular system in health and disease and to the pharmacological effects of
      cardiovascular agents via autocrine-paracrine mechanisms. Based on observations
      from experimental models of hypertension, hypertrophy, ischemia, remodelling and
      preconditioning one can assume that modulation of local KKS pathways is
      instrumental for endogenous cardio- and vasculoprotective mechanisms. The role of
      kinins as possible mediators of such protective mechanisms is not only based on
      the existence of their generating pathways and their release, but also on
      observations that kinins, when given locally or being increased by inhibition of
      their breakdown, exert beneficial cardiovascular effects, whereas antagonism of
      their receptors worsens these effects. Indispensable pharmacological tools like
      ACE inhibitors and kinin receptor antagonists have helped to clarify these
      assumptions, which are now further elucidated by molecular biology and by
      clinical research. Especially the wealth of experimental and clinical findings
      with ACE inhibitors present a continuous challenge to investigate the role of
      kinins in the cardiovascular system and to have a closer look at the
      interdependence of KKS and the Renin-Angiotensin-System (RAS). Within our decade
      one might not only reach a clearer molecular perception of kinins in the
      cardiovascular system, and their role in human health and disease, but might also
      come to improved innovative treatment by modulation of the KKS pathways.

PMID- 8856153
TI  - Removal and restoration of epithelial chloride secretory activity of kinins by
      gene manipulation.
AB  - Kinins are known to stimulate electrogenic chloride secretion in many mammalian
      epithelia, including those of the airways and the alimentary tract. In this study
      the chloride secretory activity of lysylbradykinin (LBK) on murine colonic
      epithelium has been examined, specifically to discover the primary and final
      effector mechanisms in this process, i.e., which kinin receptors are involved and
      which chloride channels are responsible for chloride secretion. The approach used
      was to modify the mice genetically and assess the effects on kinin mediated
      chloride secretion using voltage clamping at zero potential. Briefly, LBK
      increased SCC in mouse colon by approximately 150 microA cm-2 with an EC50 of
      approximately 5 nM. In null CF mice LBK, 1 microM had no effect on chloride
      secretion, but reduced SCC due to K+ secretion. This effect is normally masked in
      wild-type tissues by dominant chloride secretion, but can be shown to occur to
      the same extent by measuring K+ secretion with radioisotopes. Null CF mice
      produce no cftr, but CFTR was introduced into CF mice by injecting a YAC
      containing the human CF gene into the pronucleus of CF zygotes. Colonic epithelia
      from mice with the incorporated YAC showed the same sensitivity to LBK as wild
      type tissues and achieved the same maximal chloride secretory response. Colonic
      epithelia from mice in which the B2r gene had been disrupted showed no response
      to LBK at normally supramaximally effective concentrations, although responses to
      other secretagogues were normal. Similarly des-Arg-BK caused no acute chloride
      secretory response in colonic epithelia from B2 knockout mice, however small
      responses appeared if tissues were incubated in vitro for 3-6 h. It is concluded
      that cftr chloride channels and B2rs are required for electrogenic chloride
      secretion. Further CFTR can replace cftr with no effect on either the sensitivity
      or extent of chloride secretion. In vitro, colonic epithelia may generate B1rs
      which, upon activation, have a minor effect on chloride secretory activity.

PMID- 8856154
TI  - Bradykinin and nitric oxide in infectious disease and cancer.
AB  - Vascular pathophysiology at the sites of bacterial infection and cancerous
      tissues share numerous common events similar to inflammatory tissue. Among them
      enhanced vascular permeability is the universal and hallmark event mediated by
      bradykinin. All 16 or more bacterial or fungal proteases we have examined
      activated one or more steps of the kinin generating Hageman-factor-kallikrein
      cascade. In the meantime, most of the microbial proteases rapidly inactivated
      various plasma inhibitors such as alpha 1-protease inhibitor and alpha 2
      macroglobulin. In addition to the extracellular proteases, bacterial cell wall
      components (negatively charged LPS) of gram-negative bacteria and teichoic acid
      moieties of gram-positive bacteria activate the Hageman-factor-kallikrein system
      and exert hypotensive effects via kinin generation. Endotoxin (LPS) also induces
      nitric oxide synthase (NOS) which appears to exhibit a rather slow, but
      significant, effect in relaxing the vascular tone of the infected animal (thus
      hypotension). Furthermore, bacterial proteases can activate the matrix
      metalloproteinase (collagenase) resulting in exacerbation of tissue injury in the
      diseased animal. Many tumor cells or tissues excrete plasminogen activator, and
      hence activate plasminogen. The plasmin thus generated activates procollagenases,
      as well as the Hageman-factor-kallikrein system, resulting in pronounced
      extravasation. Fluid accumulation in pleural and ascitic carcinomatoses is
      largely due to the activated bradykinin-generating system. We can also
      demonstrate and control enhanced vascular permeability using kallikrein
      inhibitors, especially the polymer-conjugated soybean trypsin inhibitor which
      exhibits a prolonged plasma t1/2, kinin antagonists, NOS inhibitors, NO
      scavengers, inhibitors of prostaglandins and others. Bacterial proteases induce
      shock in mice which can be prevented by the soybean trypsin inhibitor by blocking
      the kallikrein-kinin cascade. Therapeutic use of kinin antagonists and a
      kallikrein inhibitor has been made for infectious diseases such as septicemia and
      in tumor pathology.

PMID- 8856155
TI  - Activation of the contact and fibrinolytic systems after intravenous
      administration of endotoxin to normal human volunteers: correlation with the
      cytokine profile.
AB  - Severe progressive failure of multiple organ systems has emerged during the past
      three decades as a common cause of death among patients in intensive care units.
      Sepsis is now better defined as systemic inflammatory response syndrome (SIRS),
      but its mortality rate has not changed and it continues to be a major health
      problem. Endotoxin interacts with plasma proteins and contributes to the
      pathophysiology of SIRS. Information is limited on the effect of endotoxin on
      human coagulation and fibrinolytic proteins in vivo, as well as on the cell
      response involved in the cytokine cascade. For this reason we performed
      quantitative assays to establish the sequence of events that occurs in vivo in
      the regulation of the contact and fibrinolytic pathways as well as in the
      cytokine cascade as a response to a single dose administration of endotoxin to
      normal non-smoking human volunteers.

PMID- 8856156
TI  - Efficacy and tolerability of Icatibant (Hoe 140) in patients with moderately
      severe chronic bronchial asthma.
AB  - Bradykinin (BK) has been identified as a mediator in human bronchial asthma. The
      current phase II study was designed as a multicentered, double blinded,
      randomized, placebo-controlled, parallel-group pilot study to investigate the
      efficacy of the B2 BK receptor antagonist Icatibant in adult patients with
      chronic asthma. Patients were treated t.i.d. with 900 micrograms or 3000
      micrograms of nebulized Icatibant, or placebo. Treatment was for 4 weeks,
      followed by a 2-week placebo run-out. Icatibant was very well tolerated, and led
      to a dose-dependent improvement in objective pulmonary function tests (PFTs)
      measured by the investigators (e.g. FEV1 and PEFR). At 3 mg t.i.d., a
      statistically significant difference (p < 0.001) between Icatibant and placebo of
      about 10% was achieved after 4 weeks of treatment for all PFTs. At 900 micrograms
      t.i.d., the improvement in PFTs was smaller. By contrast, no clinically relevant
      improvement in global symptom score (nor a reduction of rescue medication) was
      found when compared with placebo. The observed improvement in objective PFTs
      started between weeks one and two, gradually increased until the end of active
      treatment, and slowly decreased during the placebo run-out phase, suggesting an
      anti-inflammatory effect. No acute bronchodilator effect was found. In
      conclusion, Icatibant showed a profile expected for an anti-inflammatory asthma
      drug.

PMID- 8856157
TI  - The bradykinin antagonist CP-0597 can limit the progression of postischemic
      pancreatitis.
AB  - Bradykinin mediates the inflammatory process of acute pancreatitis characterized
      by an increase of microvascular permeability, vasodilation and leukocyte
      activation. These phenomena are characteristic also for the ischemia/reperfusion
      injury of the pancreas, which in time is considered a causative factor in the
      pathogenesis of acute pancreatitis. The aim of this study was to investigate the
      influence of the bradykinin B2 receptor antagonist CP-0597. After complete
      ischemia/reperfusion of the pancreas in rats there is progression from
      postischemic acute edema to necrotizing pancreatitis over a reperfusion period of
      5 days. In 8 Sprague-Dawley rats (treatment group) 18 micrograms/kg/h CP-0597 was
      administered intraperitoneally over 5 days with an osmotic minipump starting 15
      min before release of 2 h ischemia. Animals of the placebo group (n = 8) were
      identically treated, but received the solvent, phosphate buffer. Animals of a
      control group (n = 7) underwent sham operation without ischemia. After 5 days the
      animals were sacrificed for histology. No morphological changes of the pancreatic
      gland were observed in the control group. Ischemia for 2 h resulted in
      necrotizing pancreatitis with high mortality (4/8 animals) during the reperfusion
      period of 5 days. In contrast, all animals in the treatment group survived
      without clinical or histological signs of necrotizing pancreatitis.

PMID- 8856158
TI  - Translocation of the neutrophil kinin moiety and changes in the regulation of
      kinin receptors in inflammation.
AB  - A molecular response to cell injury is the formation of chemotactic mediators
      that attract neutrophils to sites of inflammation. The question whether
      neutrophils contribute to circulating levels of kinins was examined in infections
      and inflammatory disorders. This novel hypothesis was tested using circulating
      neutrophils harvested from patients with tuberculosis meningitis and pneumonia.
      These neutrophils showed a distinct loss of only the kinin moiety from the
      kininogen located on the external surface. A similar loss of the kinin peptide
      was observed on the synovial fluid neutrophils obtained from the swollen,
      inflamed joints of patients with rheumatoid arthritis. The intriguing question is
      whether the circulating neutrophils simply reflect those cells re-entering the
      circulation from sites of inflammation. Anti-peptide antibodies to the peptide
      loops of cloned B1 and B2 receptors have provided a powerful probe for the
      cellular identification of the two kinin receptor families. We report the first
      localisation of B1 receptors on the basement membranes of bronchopulmonary cells
      and the surrounding fibrous stroma in transbronchial biopsies taken from patients
      with interstitial lung disease associated with progressive systemic sclerosis.
      Although binding of labelled bradykinin to neuronal membranes has been
      demonstrated, this is the first conclusive evidence for the presence of B1 kinin
      receptors in the neurons of human hypothalamus, caudate nucleus and the
      substancia gelatinosa of the spinal cord. Mapping of the B2 receptors in human
      tissues shows upregulation on the neutrophils gathered from inflamed joints, and
      absence from cell membranes of acutely rejecting transplant kidney. In addition,
      B2 receptors have also been demonstrated in neurons of the brain hypothalamus,
      caudate nucleus and cerebral cortex. Kinin receptor localisations in human tissue
      has considerable therapeutic implications.

PMID- 8856159
TI  - Vasomotor and permeability effects of bradykinin in the cerebral
      microcirculation.
AB  - All components of an intracerebral kallikrein-kinin system have been described.
      Thus, bradykinin (BK) acting from the parenchymal site as well as from the blood
      site may influence cerebral microcirculation. BK is a potent dilator of extra-
      and intraparenchymal cerebral arteries when acting from the perivascular site.
      The vasomotor effect of BK is mediated by B2 receptors which appear to be located
      at the abluminal membrane of the endothelial cell. The effect of BK is mediated
      by NO. prostanoids, free radicals, H2O2 or leukotrienes depending on the animal
      species and on the location of the artery. Selective opening of the blood-brain
      barrier for small tracers (Na(+)-fluorescein; MW, 376) has been found in cats
      during cortical superfusion or intraarterial application of BK. This leakage is
      mediated by B2 receptors located at the luminal and abluminal membrane of the
      endothelial cells. Formation of brain edema has been found after ventriculo
      cisternal perfusion or interstitial infusion of BK. This can be explained by
      increase of vascular permeability and cerebral blood flow due to arterial
      dilation thus enhancing driving forces for the extravasation. An increase of the
      BK concentration in the interstitial space of the brain up to concentrations
      which induce extravasation, dilatation and oedema formation has been found under
      several pathological conditions. Thus, BK may be involved in oedema formation
      after cold lesion, concussive brain injury, traumatic spinal cord and ischemic
      brain injury. The mediator role of BK in brain edema is further supported by
      therapeutic results. Brain swelling due to cold lesion or ischemia could be
      diminished by treatment with kallikrein-inhibitors. Similarly, dilatation of
      cerebral arterioles after concussive brain injury was reduced by blockade of B2
      receptors. Thus, all criteria favour BK as one mediator of vasogenic oedema.

PMID- 8856160
TI  - Development of hyperthermia and hyperalgesia following intracerebroventricular
      administration of endotoxin in the rat: effect of kinin B1 and B2 receptor
      antagonists.
AB  - The present study investigated the development of hyperthermia and thermal and
      mechanical hyperalgesia following i.c.v. injections of E. coli lipopolysaccharide
      (LPS) in rats. LPS increased core temperature and this was prevented by i.c.v.
      administration of HOE 140, a kinin B2 receptor antagonist or by indomethacin
      i.c.v. or i.v. B1 receptor antagonists had no effect. LPS induced thermal and
      mechanical hyperalgesia which was reversed by i.c.v. HOE 140 and indomethacin
      i.c.v. and i.v., but not by B1 receptor antagonists. These results indicate that
      injections of endotoxin to the CNS induces hyperthermia and hyperalgesia and that
      kinins, acting on centrally located B2 receptors, and prostanoids are involved.

PMID- 8856161
TI  - Permeability of the blood brain barrier by the bradykinin agonist, RMP-7:
      evidence for a sensitive, auto-regulated, receptor-mediated system.
AB  - The novel bradykinin (BK) analog, RMP-7, was characterized in a series of in
      vitro tests to establish its selectivity as a B2 agonist. It was then used to
      study bradykinin's role in permeabilizing the blood brain barrier (BBB) and blood
      brain-tumor barrier (BTB), using an RG2 rat glioma model. These studies
      demonstrated that: (1) B2 receptor stimulation permeabilizes both the BBB and BTB
      in a dose-related fashion with greater effects observed in brain tumor-associated
      tissue, (2) the increased permeability is sensitive, rapid and transient, and (3)
      tachyphylaxis occurs with continuous agonist administration, suggesting
      autoregulation of the system's effects. These data therefore support the
      existence of a sophisticated, responsive and tightly regulated BK system whose
      activity modulates the permeability of the BBB.

PMID- 8856162
TI  - The kallikrein/kinin system and kinin antagonists in trauma.
AB  - These data and others indicate that the kallikrein/kinin system is activated in
      both systemic and central nervous system trauma and that specific kinin
      antagonists are active in animal models of systemic and CNS trauma. In addition,
      preliminary data in humans suggest that kinin antagonists may have a role in the
      management of traumatic brain injury. Clearly, further studies in these
      indications are indicated.

PMID- 8856163
TI  - In vivo characterization of B2 receptors mediating hypotension in anesthetized
      rabbits and guinea pigs.

PMID- 8856164
TI  - Biosynthesis of endothelium-derived nitric oxide by bradykinin as endogenous
      precursor.

PMID- 8856165
TI  - Lack of contribution of circulatory kinin elevated by captopril to induce
      hypotension in normotensive and hypertensive rats.
AB  - Captopril (10 mg/kg, i.p.) increased the arterial bradykinin (BK) level (Art-BK)
      of non-treated Sprague-Dawley rats (SD), determined by an ELISA, from 10.8 +/-
      3.2 pg/ml to 32.9 +/- 5.4 pg/ml significantly (p < 0.05, n = 6). Intravenous
      infusion of BK (100-3000 ng/kg/min) dose-dependently increased heart rate (HR)
      and decreased mean blood pressure (MBP), the former at lower doses than the
      latter, and the hypotensive response became significant at 3000 ng/kg/min. Art-BK
      determined during infusion of the lowest dose of BK (100 ng/kg/min) was 12 times
      the endogenous Art-BK after captopril administration. In spontaneously
      hypertensive rats, Wistar Kyoto rats, and deoxycorticosterone acetate-salt
      treated hypertensive rats, Art-BK (450-1280 pg/ml) determined during intravenous
      BK-infusion (1000-3000 ng/kg/min), which induced significant hypotension, was 20
      to 100 times the endogenous Art-BK (4.5-64 pg/ml) with captopril treatment. These
      results suggest that the increased Art-BK due to inhibition of kinin degradation
      by captopril could not account for the hypotension due to this angiotensin
      converting enzyme inhibitor in normotensive and hypertensive rats.

PMID- 8856166
TI  - Modulation of kinin outflow from isolated perfused rat hearts by endothelin-1.
AB  - Bradykinin has previously been shown to suppress ET-1 secretion by endothelial
      cells. In the present study, rat isolated hearts have been perfused with Krebs
      solution using the Langendorff method. Immunoreactive bradykinin (IRBK) was
      measured in the perfusate and the basal level was found to be constant for up to
      3 h. Ten min perfusions of the hearts with ET-1 at concentrations of 0.2-20 pM
      produced a dose-related suppression of kinin outflow by over 90% (P < 0.05). At
      these concentrations ET-1 had no detectable effect on the coronary vasculature or
      ECG. At 200 pM ET-1 and above, the hearts showed arrhythmias of increasing
      severity, accompanied at the highest doses by marked coronary constriction and an
      increase in IRBK outflow.

PMID- 8856167
TI  - Kinin release from normally perfused and ischaemic isolated rat hearts: effect of
      strain.
AB  - The release of kinin during 30 min of left descending coronary artery was
      observed in WKY, SHR and SD rat isolated hearts. The kinin levels were compared
      with the ECG abnormalities in these strains. It was observed that low level of
      kinin could not be a reason for increased ECG abnormalities. IRBK in the
      perfusate was also characterised.

PMID- 8856168
TI  - The release of kininase from rat isolated hearts during myocardial ischaemia.
AB  - BK destroying activity was observed in rat isolated heart perfusates. BK was
      optimally degraded at pH 8.4 in rat heart. The results indicated that myocardial
      kinin degradation was due to ACE and a serine protease. These results suggest
      that bradykinin may have some cardioprotective role during myocardial ischaemia
      at acidic pH.

PMID- 8856169
TI  - Blood pressure sensitivity to salt in rats with low urinary kallikrein excretion.
AB  - We evaluated if a rat strain inbred for reduced urinary kallikrein excretion
      differs from normal-kallikrein Wistar rats regarding blood pressure in basal
      conditions and during alterations in sodium balance. Low-kallikrein rats showed
      greater systolic blood pressure values (125 +/- 3 vs. 114 +/- 2 mmHg in controls,
      P < 0.01) at 9 weeks of age. Systolic blood pressure was increased after 20 days
      of dietary sodium loading in the low-kallikrein group and remained unchanged in
      controls (150 +/- 6 vs. 112 +/- 2 mmHg, P < 0.01) and this effect was associated
      with a reduced cumulative excretion of sodium (23% less in the low-kallikrein
      group compared with controls, P < 0.01). Urinary creatinine excretion was
      decreased by sodium loading in both groups, and this effect was more pronounced
      in the low-kallikrein group. The group-difference in urinary kallikrein excretion
      found in basal conditions (2.49 +/- 0.10 vs. 7.78 +/- 0.53 Pkat/100 g body
      weight, P < 0.01) was enhanced by high salt diet (1.05 +/- 0.21 vs. 8.31 +/- 0.70
      Pkat/100 g body weight, P < 0.01). The ratio of heart weight to body weight was
      significantly greater in low-kallikrein rats (331 +/- 7 vs. 275 +/- 4 mg/100 g
      body weight, P < 0.01), whereas the ratio of kidney weight to body weight was
      lower (329 +/- 5 vs. 370 +/- 8 mg/100 body weight, P < 0.01). Our results
      indicate that a genetically-determined defect in urinary kallikrein excretion is
      associated with a greater blood pressure sensitivity to salt, possibly due to
      altered renal sodium handling.

PMID- 8856170
TI  - Pressor action of angiotensin I at the ventrolateral medulla: effect of selective
      angiotensin blockade.
AB  - In this study we explored the possibility that angiotensin-(1-7) (Ang-(1-7)) is
      involved in the control of blood pressure at the rostral ventrolateral medulla
      (RVLM) by determining the effect of angiotensin antagonists (DuP 753 and A-779)
      and the effect of the angiotensin converting enzyme inhibitor, ramiprilat on the
      pressor action produced by angiotensin I (Ang I). The pressor effect produced by
      bilateral microinjection of Ang I into the RVLM of anesthetized rats was not
      significantly altered by DuP 753 or by the ACE inhibitor ramiprilat. Conversely,
      the Ang-(1-7) antagonist, A-779, reduced significantly the pressor effect
      produced by Ang I. These data suggest that in our experimental condition Ang I
      was preferentially converted to Ang-(1-7) at RVLM, or that Ang I and/or one of
      its fragments acts through a receptor blocked by A-779.

PMID- 8856171
TI  - Reduction by a kallikrein inhibitor of the increased nasal airway resistance of
      allergic patients after antigen challenge.
AB  - Kallikrein activity in nasal lavage fluid, which was measured with a synthetic
      substrate, Pro-Phe-Arg-methylcoumarilamide, was increased in accordance with the
      severity of the symptoms of house-dust-mite allergic rhinitis. Antigen challenge
      was applied to patients with allergic rhinitis by placing a disk containing
      allergen on the nasal mucosa of the right inferior turbinate. Kallikrein
      activities and kinin levels in the nasal lavage fluid had increased significantly
      15 min after the antigen challenge. These increases were accompanied by a marked
      increase in nasal airway resistance 15 min after antigen challenge. Pretreatment
      of the patients with camostat mesilate (60 mg/kg, p.o), a non-peptide serine
      proteinase inhibitor clinically used in Japan, inhibited the kallikrein activity
      in the nasal lavage fluid. The increase in nasal airway resistance after antigen
      challenge was also markedly reduced by oral administration of the inhibitor,
      indicating involvement of the kallikrein-kinin system in induction of the nasal
      symptoms.

PMID- 8856172
TI  - Bradykinin levels during experimental nasal infection with rhinovirus and
      attenuated influenza virus.

PMID- 8856173
TI  - The contact system in experimental enterocolitis.

PMID- 8856174
TI  - Immunoreactive B1 receptors in human transbronchial tissue.

PMID- 8856175
TI  - Immunolocalisation of the kinin moiety and bradykinin (B2) receptors on synovial
      fluid neutrophils in rheumatoid arthritis.

PMID- 8856177
TI  - Effect of a serine proteinase inhibitor from Leucaena leucocephala on plasma
      kallikrein and plasmin.

PMID- 8856176
TI  - Involvement of bradykinin B1 and B2 receptors in human PMN elastase release and
      increase in endothelial cell monolayer permeability.
AB  - Bradykinin (BK) is a potent inflammatory mediator, which can release other
      inflammatory mediators by interacting with bradykinin B1 and B2 receptors. The
      role of kinins in regulating human PMN elastase release was studied. BK induced
      elastase release 5-fold over basal levels. Elastase release was inhibited by both
      B1 and B2 receptor antagonists. A specific B1 agonist des-Arg10-KD increased
      elastase release 4-fold. Since elastase has been implicated in vascular leak, the
      effect of BK on endothelial cell monolayer (EM) permeability was assessed. BK
      increased EM leak (I125 flux) across the EM, whereas des-Arg10-KD was inactive.
      When co-cultured with human umbilical vein endothelial cells, des-Arg10-KD
      treated PMNs increased EM leak by 35%. The elastase inhibitor AAVPK blocked des
      Arg10-KD-induced leak by 80% suggesting that elastase is responsible for the
      increase in permeability. It is concluded that BK causes increased leak by
      inducing PMN elastase release via activation of both B1 and B2 receptors. BK
      blockade and elastase inhibition may be beneficial in inflammatory diseases such
      as ARDS which is characterized by increased lung permeability and both kinin and
      PMN activation are thought to participate.

PMID- 8856178
TI  - Nociception and inflammatory hyperalgesia in B2 bradykinin receptor knockout
      mice.

PMID- 8856179
TI  - Pathophysiological and possible physiological roles of kinins in the pancreas.
AB  - The i.v. infusion of a low dose of the cholecystokinin agonist caerulein elicited
      a sustained secretion of amylase into the biliopancreatic duct of rats.
      Pretreatment with the bradykinin antagonist icatibant (Hoe-140) had no effect on
      unstimulated amylase release and did not affect caerulein-induced amylase
      secretion. An i.v. infusion of bradykinin in doses not producing a pancreatic
      oedema elicited an increase in pancreatic juice production lasting 20-40 min
      after the end of the infusion. This pro-secretory effect was also visible at
      higher doses in captopril-pretreated rats producing an oedema similar to that
      observed in caerulein-induced pancreatitis. Using the Monastral blue method, it
      was found that the kininase II blocker captopril induced an opening of
      endothelial gaps in pancreatic capillaries. This effect was blocked by icatibant
      suggesting that kinins are formed in the pancreas under basal conditions. Thus,
      kinins appear not to be involved in the regulation of the production of digestive
      enzymes. However, kinins may have a modulatory role in the production of
      pancreatic juice and in the microcirculatory regulation in the pancreas.

PMID- 8856180
TI  - The role of kallikrein-kinin system in the diabetic placental rats.

PMID- 8856181
TI  - Cardiac kallikrein in hypertensive and normotensive rats with and without
      diabetes.
AB  - This study examined the effects of streptozotocin-induced diabetes on blood
      pressure and cardiac tissue kallikrein levels in WKYR and SHR. Streptozotocin
      induced diabetes caused significant (p < 0.001) increase in SBP and DBP in WKYR
      and SHR as compared with their respective controls. We also observed that the
      active cardiac tissue kallikrein levels reduced greatly (p < 0.001) in diabetic
      WKYR and SHR than the normal rats. These findings suggest for the first time that
      the cardiac tissue kallikrein formation may have a greater role in the regulation
      of blood pressure and cardiac function.

PMID- 8856182
TI  - Bradykinin excretion is increased in severely hyperglycemic streptozotocin
      diabetic rats.
AB  - The renal kallikrein-kinin system (KKS) was studied in pair-fed streptozotocin
      (STZ)-induced diabetic rats and compared with age-matched controls. Twelve weeks
      after STZ injection, rats were normotensive, showed hyperglycemia, proteinuria,
      polydipsia and reduced glomerular filtration rate (GFR) and body weight. The
      activities of urinary prekallikrein (PKLK) and kallikrein (KLK) were reduced
      accompanied by an up to 3-fold increase of bradykinin (BK) excretion compared to
      controls. The increased BK excretion suggests that the renal KKS in STZ-diabetes
      is activated and that the reduction in urinary PKLK and KLK activity may be due
      to an increased consumption of these enzymes or to a negative feedback mechanism.
      The stimulation of the renal KKS in STZ-diabetes could reflect an attempt of the
      organism to balance glomerular hypertension.

PMID- 8856183
TI  - The role of the kallikrein-kinin system in type I diabetes (insulitis).

PMID- 8856184
TI  - The relationship between urinary kallikrein and glomerular filtration rate (GFR)
      in type-1 diabetes: studies with lithium.

PMID- 8856185
TI  - Kininogen changes in human plasma following a test meal or insulin
      administration.
AB  - In healthy, fasted volunteers, the ingestion of a test meal produced within 30
      min, a decrease of ca. 40% of high molecular weight kininogen (HK) in plasma.
      Return to control (fasting) levels occurred after 90-120 min. Low molecular
      weight kininogen (LK) remained unchanged or was slightly elevated. On another
      occasion, the same group of fasted volunteers received an intravenous, euglycemic
      clamped infusion of insulin. This treatment reproduced the effects of the test
      meal on HK. Insulin had no effect on kininogen following incubation with plasma
      or whole blood. Slight systemic hypotension and increased leg muscle blood flow
      accompanied postprandial plasma kininogen change. It is suggested that such
      vascular changes may in part, be due to bradykinin (BK) released from HK cleaved
      at vascular, possibly endothelial sites activated by insulin following its
      release by alimentary stimulation. A decreased capacity to release BK due to
      absence of, or lowered sensitivity to, insulin may play a role in the origin of
      hypertension in diabetes.

PMID- 8856186
TI  - Activation of the complement, coagulation, fibrinolytic and kallikrein-kinin
      systems during attacks of hereditary angioedema.

PMID- 8856187
TI  - Activation of factor XII and cleavage of high molecular weight kininogen during
      acute attacks in hereditary and acquired C1-inhibitor deficiencies.
AB  - Hereditary and acquired C1-inhibitor (C1-INH) deficiencies (hereditary
      angioedema, HAE and acquired angioedema, AAE) are characterized by episodic
      increases in vasopermeability due to kinin release. Despite continuously
      defective C1-INH levels, symptoms only recur occasionally suggesting an episodic
      generation of pathogenetic factors induced by activation of the protease systems
      regulated by C1-INH. We evaluated activation of factor XII by measuring plasma
      levels of FXIIa with a commercial ELISA and cleavage of high molecular weight
      kininogen by performing SDS PAGE and immunoblotting analysis during 5 attacks in
      5 different patients with HAE and during 7 attacks in 3 patients with AAE. The
      patients were also studied during remission. We confirmed our previous data
      indicating that during attacks both HAE and AAE patients had very high levels of
      cleaved HK (p < 0.0001) whereas during remission cleaved HK levels were normal in
      HAE and significantly increased in AAE (p < 0.0001). Both in HAE and in AAE,
      plasma levels of FXIIa were normal during remission and significantly increased
      during acute attacks (p = 0.0126; p = 0.0003). Our data suggest that the
      activation of a contact system is required to produce clinical symptoms.

PMID- 8856188
TI  - Bradykinin release from high molecular weight kininogen in surgical ICU patients.
AB  - The purpose of this prospective study was to characterize kininogens in plasma
      from surgical ICU patients. Thirty-five patients, ages 19-79 years, were divided
      into 2 groups: sepsis (defined by standard criteria) and nonsepsis. Studies of
      proteolytic degradation of H-kininogen showed degradation in both patient groups
      compared to healthy controls. Functional quantification of prekallikrein showed a
      reduction of prekallikrein in plasma from both patient groups. Functional
      quantification of kininogens by a CPI (cysteine proteinase inhibitor) assay
      showed no significant differences between the patients and the controls.
      Immunological levels of H-kininogen and total kininogen were not significantly
      different from normal plasma. No differences could be detected between the two
      patient groups in any of the parameters studied. In conclusion, this study
      supported contact activation taking place in surgical ICU patients, a partial
      kinin release and a consumption of prekallikrein has taken place in vivo.

PMID- 8856189
TI  - Further evidence of bradykinin involvement in septic shock: reduction of kinin
      production in vivo and improved survival in rats by use of polymer tailored SBTI
      with longer t1/2.
AB  - Involvement of bradykinin in septic shock and its therapeutic endeavor using
      soybean trypsin inhibitor (SBTI, Kunitz type) were investigated in an in vivo
      model of septic shock induced by pseudomonal elastase. Pseudomonal elastase
      injection at 0.5 mg/kg i.v. to guinea pigs resulted in elevation level of
      bradykinin in the blood from < 1 ng/ml to 25 ng/ml which was accompanied by a
      drop of mean arterial blood pressure (MABP) (about 45 mmHg). When native soybean
      trypsin inhibitor (SBTI, Kunitz type, 20 kDa) was injected, into this model,
      induction of bradykinin generation and hypotension by the bacterial protease
      treatment was completely obliterated as judged by the both levels of bradykinin
      and MABP. Specifically, by the treatment with SBTI, bradykinin levels did not
      increase and the drop of the blood pressure was minimal (< 10 mmHg) in this time
      frame (< 30 min). We designed and prepared succinylated gelatin-conjugated SBTI
      (suc-gel SBTI) with enlarged molecular mass (M(r) approximately 110,000) and
      higher area under the curve of the plasma concentration, which exhibits about 6
      times longer plasma half-life (t1/2) and about 4 times larger area under the
      curve of plasma concentration. Suc-gel-SBTI suppressed the pseudomonal protease
      induced shock much more effectively than native SBTI, the conjugate exhibited its
      effect for more than 3 h, while the native SBTI showed the effect only within 2 h
      after i.v. injection.

PMID- 8856190
TI  - Does resistance to endotoxin in primates correlate with levels of plasma
      prekallikrein?
AB  - Increased release of BK by HK hydrolysis has been correlated with the severity of
      hypotension in septic patients and animals challenged with gram-negative bacteria
      or endotoxin (ETX). Since HK hydrolysis in vivo is attributed mainly to the
      catalytic reaction of kallikrein (KAL) formed by activation of plasma PK, I
      tested whether the known resistance to ETX-rhesus and baboon > man and chimp
      correlated with PK levels. Immunoblots and amidolytic assays showed that PK
      levels did not correlate. They were in rhesus and man > baboon and chimp. Also,
      PK did not correlate with levels of other modulators of free KAL levels in plasma
      factor XII, HK and KAL inhibitors. Nonetheless, the distribution of PK and its
      activation products in plasmas activated with kaolin at 37 degrees C is analogous
      in the 4 primates, suggesting a similar mechanism for KAL inhibition in vitro.
      The results suggest that factors not yet known must contribute to the
      differential resistance of primates to ETX. Knowledge of these factors will help
      in prophylaxis and therapy of septicemia.

PMID- 8856192
TI  - Tissue kallikrein excretion in acute and chronic renal transplant rejection.

PMID- 8856191
TI  - Activation of bradykinin generating cascade by Vibrio cholerae protease.

PMID- 8856193
TI  - Activity of leukocyte elastase in patients' plasma is a significant indicator of
      atopic diseases.
AB  - It is commonly known that activation of plasma kallikrein-kinin system is of
      great importance in the pathogenesis of atopic diseases. Plasma kallikrein most
      likely activates other arginine-esterases in human plasma. Diagnostic and
      prognostic values of the total arginine-esterase activity and the activity of
      leukocyte elastase (LE) in plasma of patients with allergic rhinitis (AR), atopic
      bronchial asthma (ABA) and atopic dermatitis (AD) were examined in this study.
      Our results demonstrate that the level of arginine-esterase activity was slightly
      elevated only in plasma of patients with ABA (424 +/- 24; N-360 +/- 20 mU/ml),
      but not with AR and AD. Elastase-like activity in human plasma proved to be a far
      more informative indicator of the atopic states than arginine-esterase activity.
      In plasma of patients with AR, ABA and AD the activity of LE exceeded the normal
      level in 1.7, 1.8, and 2.4 times, respectively. Treatment of these atopic states
      with Ditec (Boehringer Ingelheim) led to some improvements of the patient'
      states. The main component of this drug (disodium chromoglycate) inhibited the
      activity of leukocyte elastase in experiments in vitro.

PMID- 8856194
TI  - Role of neutrophil kinin in infection.

PMID- 8856195
TI  - Interstitial inflammation and scarring: messages from the proximal tubular cell.

PMID- 8856196
TI  - Cell calcium and arterial blood pressure.

PMID- 8856197
TI  - How to diagnose and how to interpret microalbuminuria in the diabetic patient.

PMID- 8856198
TI  - The diabetic patient with ESRD: how to select the modality of renal replacement.

PMID- 8856199
TI  - Mortality in diabetic nephropathy: the importance of the QT interval.

PMID- 8856200
TI  - Renal atheroembolic disease: the Cinderella of nephrology?

PMID- 8856201
TI  - Non-dialytic management of the patient with acute renal failure.

PMID- 8856202
TI  - Hepatitis C in transplantation.

PMID- 8856203
TI  - Hepatitis G virus: an old, but newly discovered hepatotropic virus--is it of
      interest for the nephrologist?

PMID- 8856204
TI  - Will pimagidine improve survival of diabetics on dialysis?

PMID- 8856205
TI  - Alteration of growth-related proto-oncogene expression in diabetic glomeruli by a
      specific endothelin receptor A antagonist.
AB  - BACKGROUND: The early phase of glomerular growth in diabetic rats is accompanied
      by increased c-fos and c-jun expression. The renal endothelin (ET)-1 mRNA levels
      increased with the progression of diabetic nephropathy. This study was designed
      to assess whether glomerular mRNA expression of growth-related proto-oncogenes in
      diabetic rat glomeruli is affected by a specific ET receptor A antagonist,
      FR139317. METHODS: Diabetes was produced by streptozotocin (STZ) injection.
      Animals were divided into four groups: (1) untreated diabetic rats (n = 25); (2)
      FR139317-treated diabetic rats (n = 20); (3) control non-diabetic rats (n = 20);
      and (4) FR139317-treated controls (n = 20). FR139317 treatment was continued for
      24 weeks. c-myc, c-fos, c-jun and proliferating cell nuclear antigen (PCNA) mRNA
      expression in rat glomeruli from each group (n = 7) at 4, 12 and 24 weeks after
      STZ or saline injection was evaluated. RESULTS: Glomerular mRNA levels for c-myc,
      c-fos, c-jun and PCNA in group 1 increased with the progression of diabetic
      nephropathy (24 weeks: c-myc, 4.6-fold; c-fos, 3.8-fold; c-jun, 4.2-fold; and
      PCNA, 4.4-fold). FR139317 treatment attenuated increases in glomerular mRNA
      levels of these genes (24 weeks, c-myc, 0.4-fold; c-fos, 0.4-fold; c-jun, 0.5
      fold; and PCNA, 0.4-fold) in group 2. However, FR139317 did not affect mRNA
      levels in control glomeruli. CONCLUSIONS: These data suggest that FR139317 may
      protect against glomerular injury of diabetes in rats by reducing mRNA levels of
      growth-related genes.

PMID- 8856206
TI  - Actions of endothelin-1 on calcium homeostasis in Madin-Darby canine kidney
      tubule cells.
AB  - BACKGROUND: In both ischaemic and nephrotoxic models, renal failure is associated
      with increased endothelin-1 (ET-1) and cell calcium overload, and ET receptor
      antagonists are protective. Vascular and tubular actions of endothelins appear to
      be involved. This study examines the actions of ET-1 on intracellular Ca
      ([Ca2+]i) in the tubule model cell line MDCK (Madin-Darby canine kidney).
      METHODS: Single-cell [Ca2+]i was measured using fura-2 and actions of ET-1 were
      compared with thapsigargin, which empties IP3-sensitive intracellular Ca stores.
      RESULTS: Mean resting [Ca2+]i was 84 nM (s.e.m. 6, n = 87). 1 microM thapsigargin
      and 100 nM ET-1 each caused a transient increase in [Ca2+]i by 696 nM (s.e.m.
      160, n = 9) and 727 nM (s.e.m. 121, n = 5) respectively. After 1 microM
      thapsigargin, 100 nM ET-1 had no effect on [Ca2+]i. Oscillations in [Ca2+]i were
      frequently observed following 100 nM ET-1. In Ca(2+)-free extracellular solution,
      mean resting [Ca2+]i was reduced by 37 nM (s.e.m. 5, n = 11) and the mean
      transient increase in [Ca2+]i in response to ET-1 was 419 nM (s.e.m. 97, n = 5).
      Inhibition of the plasma membrane Ca-ATPase with La3+ halved the rate of [Ca2+]i
      removal from the cytoplasm following ET-1. The PKC inhibitor, chelerythrine (1
      microM), reduced the ET-1 induced increase in [Ca2+]i to 349 nM (s.e.m. 97, n =
      5) and also reduced the rate of removal of [Ca2+]i. Ligand binding studies
      demonstrated ETA receptor expression in MDCK cells sensitive to ET-1.
      CONCLUSIONS: ET-1 releases Ca2+ from IP3-sensitive stores in MDCK cells as well
      as stimulating extracellular Ca2+ entry leading to oscillations of [Ca2+]i. Ca2+
      responses to ET-1 are potentiated by PKC; the plasma membrane Ca-ATPase
      contributes to removal of Ca2+ from the cytoplasm.

PMID- 8856207
TI  - Angiotensinogen-M235T genotype and post-transplant hypertension.
AB  - BACKGROUND: The angiotensinogen gene has been linked to the development of
      essential hypertension, and a M235T variant of this gene, associated with
      increased plasma levels of angiotensinogen, is more common in hypertensives than
      in normotensive controls in various populations. The present study was conducted
      to examine whether the M235T variant of the angiotensinogen gene may be a risk
      factor for the development of hypertension in patients undergoing renal
      transplantation. METHODS: DNA for genetic analysis was prospectively collected
      from 269 consecutive patients undergoing kidney transplantation between 1988 and
      1993 and their corresponding donors. Presence of hypertension and graft survival
      was analysed by blinded review of all case records over a follow-up period up to
      30 months. Angiotensinogen genotype was determined by a mutagenically separated
      allele-specific polymerase-chain-reaction technique. RESULTS: While post
      transplant hypertension was present in 78% of all patients, no relationship was
      found between either donor or recipient genotype and the presence or severity of
      post-transplant hypertension. Furthermore, there was no relationship between
      angio-tensinogen genotype and graft survival during the course of the study.
      CONCLUSIONS: These findings do not support the hypothesis that the M235T variant
      of the angiotensinogen gene is a risk factor for the development of post
      transplant hypertension.

PMID- 8856208
TI  - Age and gender-related incidence of chronic renal failure in a French urban area:
      a prospective epidemiologic study.
AB  - OBJECTIVE: To determine the age- and gender-related incidence of chronic renal
      failure in a French urban area. METHODS: Prospective study of adult patients
      newly identified as having established, chronic renal failure defined by serum
      creatinine (Scr) > or = 200 mumol/l, with the cooperation of all nephrology and
      dialysis units in the Ile de France district (10,660,000 inhabitants) during a 1
      year period. RESULTS: 2775 patients (1780 males, 995 females) were referred with
      Scr > or = 200 mumol/l between July 1991 and June 1992, an overall incidence of
      260/million population. 847 had advanced renal failure (Scr > or = 500 mumol/l)
      and 541 patients (19.5%) were > or = 75 years of age. The age-related incidence
      was 92, 264, 523 and 619/million population in the age groups 20-39, 40-59, 60-74
      and > or = 75 years old, respectively. The annual incidence was twice as high in
      males than in females up to 75 years and three times as high in patients > or =
      75 years (1124 vs 356/million population). Based on the proportion of patients
      reaching end-stage renal failure within one year of referral, the minimal
      estimation of the need for supportive therapy is 81/million/year. CONCLUSIONS:
      This epidemiological study in a large French urban area indicates an incidence of
      260 patients per million population annually referred to nephrology units for
      chronic renal failure defined by Scr > or = 200 mumol/l, with a marked
      preponderance of males and a dramatic increase of incidence with age in both
      genders.

PMID- 8856209
TI  - Reduced left ventricular hypertrophy in type 1 diabetic patients with end-stage
      renal failure. A comparison between groups investigated 1977-80 and 1991-93.
AB  - BACKGROUND: During the last decade, control of hypertension, oedema, anaemia,
      uraemia, and blood glucose has improved in patients with diabetic nephropathy. We
      have investigated whether this has influenced cardiac function at the time of end
      stage renal failure. STUDY DESIGN: Echocardiographic investigations were
      performed in 26 type 1 diabetic patients evaluated for kidney transplantation and
      the results compared with those obtained in healthy controls and in a similar
      group of patients investigated in 1977-1980. RESULTS: Blood pressure was 153 +/-
      21/85 +/- 12 mmHg versus 174 +/- 17/91 +/- 9 (recent group versus early group).
      The left ventricular (LV) diameter index, a measure of volaemia, was increased in
      systole and diastole in the early but not in the recent group. Both groups had LV
      hypertrophy, but this was much less pronounced in the recent group; posterior
      wall thickness was 1.1 +/- 0.16 cm versus 1.3 +/- 0.26 cm (P = 0.0001) and LV
      mass index 132 +/- 43 g/m2 versus 166 +/- 44 g/m2 (P = 0.009). Blood pressure
      correlated significantly with indices of LV hypertrophy in the recent group.
      Systolic function was normal in both groups but diastolic function was disturbed
      in both and to the same extent, atrial systole contributing by 27 +/- 14% to
      ventricular filling. CONCLUSION: Better treatment of hypertension, fluid
      overload, and uraemia has led to less pronounced LV hypertrophy. The remaining
      correlation with blood pressure suggests that more could be gained by intensified
      antihypertensive treatment.

PMID- 8856210
TI  - The interaction of PTH and dietary phosphorus and calcium on serum calcitriol
      levels in the rat with experimental renal failure.
AB  - BACKGROUND: Renal failure results in decreased calcitriol production, a key
      factor in the development of secondary hyperparathyroidism. Phosphorus
      accumulation and high parathyroid hormone (PTH) levels, both inherent to renal
      failure, have different effects on calcitriol production; moreover, dietary
      calcium loading may have a separate inhibitory effect on calcitriol production.
      This study was designed to evaluate the relative effects of PTH and dietary
      phosphorus and calcium on serum calcitriol levels. METHODS: Renal failure was
      surgically induced and rats were divided into normal, moderate renal failure, and
      advanced renal failure based on the serum creatinine. Each group was subdivided
      and received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or high-calcium
      diet (HCaD, 1.2% Ca, 0.6% P) for 14-16 days to determine the relative effects of
      dietary calcium and phosphorus loading on serum calcitriol. In addition the
      effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h
      PTH infusion combined with either a low (0.16%) or high (1%) phosphorus diet;
      both diets had negligible calcium (< 0.05%). RESULTS: With decreasing renal
      function, PTH increased and was greater in rats fed the HPD than the HCaD; serum
      calcitriol decreased as renal function decreased and was lower in normal rats and
      rats with moderate renal failure fed a HCaD (P < 0.01). The calcitriol response
      to a PTH infusion decreased as renal function decreased (P < 0.05) but was
      greater on a low- (0.16%) than a high- (1%) phosphorus diet (P < 0.05).
      CONCLUSIONS: Dietary calcium loading either directly decreases serum calcitriol
      or acts by modifying the stimulatory effect of PTH; the stimulatory effect of PTH
      on serum calcitriol is modified by dietary phosphorus; in moderate renal failure,
      serum calcitriol levels depend on a complex interaction between PTH and dietary
      calcium and phosphorus; and in advanced renal failure, serum calcitriol levels
      are low and are difficult to stimulate, presumably because of the loss of renal
      mass.

PMID- 8856211
TI  - Response to the hepatitis B virus vaccine in haemodialysis patients: influence of
      malnutrition and its importance as a risk factor for morbidity and mortality.
AB  - OBJECTIVE: To assess if malnutrition influences the response to the hepatitis B
      virus vaccine in haemodialysis patients and whether this correlates with
      morbidity and mortality in these patients. DESIGN: A 4-year prospective open
      study. SETTING: Haemodialysis unit of a 434-bed University Hospital. PATIENTS:
      Sixty-four patients with end-stage chronic renal failure on maintenance
      haemodialysis. INTERVENTIONS: Three-dose vaccination series with recombinant
      hepatitis B virus vaccine. MEASUREMENTS: Antibody formation against the vaccine,
      predialysis serum urea, serum albumin and prealbumin, dialysis efficacy (Kt/V),
      protein catabolic rate (PCR), arm muscle circumference, triceps skinfold, serum
      parathyroid hormone concentration, mortality and morbidity (hospital days per
      year of dialysis). RESULTS: Increase in age negatively influences the formation
      of antibodies (P = 0.01), whereas serum albumin (P = 0.008) and predialysis blood
      urea concentration (P = 0.004) are positively correlated with the formation of
      antibodies. Responders had significantly higher levels of serum albumin and
      prealbumin and predialysis blood urea than non-responders. The percentage of non
      responders was higher (70%) in the group with predialysis blood urea
      concentration between 90 and 125 mg/dl than in those with predialysis blood urea
      concentrations between 176 and 225 mg/dl (14.2%). Patients with serum albumin
      levels between 3 and 3.5 g/dl were non-responders in a higher percentage (87.5%)
      than those with serum albumin levels between 4.5 and 5 g/dl (18.8%). After a 4
      year follow-up, survival was 20% higher in the responder group (P < 0.05).
      Morbidity, expressed as hospital days per year of haemodialysis, was markedly
      lower in the responder group (10.4 +/- 2 versus 32 +/- 14 days, P = 0.03).
      CONCLUSIONS: Malnutrition negatively influences the response to the hepatitis B
      virus vaccine in haemodialysis patients. Non-responders have higher morbidity and
      mortality than responders, and therefore the absence of response to the hepatitis
      B vaccine can be considered as a risk factor in the haemodialysis population.

PMID- 8856212
TI  - The adjustment of post-dialysis dry weight based on non-invasive measurements in
      children.
AB  - BACKGROUND: The clinical criteria to assess hydration status are not always
      reliable. Hence, the development of techniques to estimate more accurately post
      dialysis dry weight (DW) remains a major challenge. The present study evaluates
      the value of the inferior vena cava (IVC) diameter, plasma concentration of
      atrial natriuretic peptide (ANP), and plasma renin activity (PRA) in determining
      the DW in chronic haemodialysis children. METHODS: Twelve overhydrated
      haemodialysis patients (4 girls, 8 boys) with a mean age of 12.8 were admitted to
      the study. Clinical, electrocardiographic, telecardiographic and
      echocardiographic findings, IVC and collapsibility indices and plasma
      concentrations of ANP and PRA were investigated before and after ultrafiltration
      (UF) therapy. Twelve age-matched normal children were studied as controls.
      Analysis of variance and Dunnett's test were applied for comparisons between
      patients and controls. RESULTS: Following UF therapy the patients' mean IVC
      collapsibility index was increased from 42.3 to 53.6% and IVC index was decreased
      from 1.08 to 0.81 cm/m2, both statistically significant. The pre-UF therapy
      collapsibility and IVC indices of the patient group were significantly different
      from those of the control group (56.9% and 0.70 cm/m2 respectively). The
      patients' mean plasma concentrations of ANP were 171 +/- 47.4 pg/ml before UF,
      129 +/- 51.3 pg/ml after UF and 102 +/- 38.7 pg/ml in the control group. The ANP
      levels of the patients showed a significant decrease following the UF therapy.
      PRA was measured as 0.82 ng/ml/h before UF and 1.08 ng/ml/h after UF, but the
      increase was not statistically significant. CONCLUSIONS: Our findings revealed
      increased diameter of the IVC and plasma ANP concentrations and decreased
      collapsibility due to overhydration. Echography of IVC may be a promising non
      invasive tool to estimate the DW in haemodialysis children. Further studies
      providing normative values for the IVC indices in both haemodialysis and normal
      children are required.

PMID- 8856213
TI  - Adequacy of haemodialysis and nutrition in maintenance haemodialysis patients:
      clinical evaluation of a new on-line urea monitor.
AB  - BACKGROUND: Recent developments in urea sensing monitoring show a good agreement
      between on-line and direct dialysis quantification which permits evaluation of
      both effective dialysis efficiency and protein catabolic rate of dialysis
      patients. METHODS: Fifty chronic haemodialysis patients were enrolled in a
      prospective study using an automatic urea sensing monitor operating on spent
      dialysate (U.M. 1000, Baxter). Dietary protein intake (DPI) and energy intake
      (DEI) were carefully evaluated by a skilled dietitian over 1 week. During this
      run U.M. 1000 was used to provide urea mass removed, effective Kt/V, and
      normalized nPCR. Blood samples were drawn pre- and post-dialysis for classical
      blood-based single pool Kt/V calculations at each session. RESULTS: For all
      patients results were as follows (mean +/- SD): Effective Kt/V 1.4 +/- 0.3, nPCR
      1.2 +/- 0.3 g/Kg/day, DPI 1.2 +/- 0.3 g/Kg/day and DEI 30.1 +/- 7.2 Kcal/kg/day;
      blood-based single pool Kt/V 1.5 +/- 0.3. A strong correlation was found between
      nPCR and DPI for the 50 patients over 1 week (r = 0.75, P < 0.0001) and between
      effective Kt/V and single pool calculated Kt/V (r = 0.76). CONCLUSIONS: Urea
      Monitor 1000 is easy and convenient to use and there was a good correlation of
      the predialysis BUN and effective Kt/V with standard blood-side measurements. In
      stable haemodialysis patients who are not strongly catabolic or anabolic, the
      urea monitor measurement of nPCR correlated with DPI measured by a 7-day dietary
      record.

PMID- 8856214
TI  - The equivalent renal urea clearance: a new parameter to assess dialysis dose.
AB  - BACKGROUND: Currently the total (dialytic plus renal) urea clearance (KT) is
      computed as Kt/V plus the equivalent Kt/V (KT/VKR) provided by the renal urea
      clearance (KR). However, KT/VKR is computed with two different formulae, by Gotch
      and Keshaviah respectively. Moreover Teschan suggested a weekly KT, that is a
      multiple of Keshaviah's KT. We suggest the equivalent renal urea clearance (EKR),
      that kinetically quantifies the "time-averaged KT' and is independent of
      treatment type and schedule. METHODS: Computer simulation has been used to
      analyse the relationship between EKR, as corrected for urea volume (EKRc), and
      Kt/V. Data from 66 HD patients, of whom eight were on once-weekly and 11 on twice
      weekly HD, had been used to compare EKR with current KTs. RESULTS: For each
      individual schedule, the relationship between EKRc and Kt/V is linear and each
      ml/min of KR increases EKR by the same amount. For instance, for thrice-weekly HD
      patients, EKRc = 1 + 10 x Kt/V: so that, the critical Kt/V values of 0.8 and 1.0
      correspond to EKRc values of 9.0 and 11 ml/min respectively, independently from
      treatment type and schedule. As to the clinical data, all once- and twice-weekly
      patients had a significant KR and excellent clinical status, but most of them had
      9 < or = EKRc < 11 ml/min. After appropriate reconciliation of units, it has been
      found that kinetic KT was overestimated by about 10-12% (range, 2-23%) by
      Keshaviah and Teschan's KT, and by about 2-7% (range, 0.3-15%) by Gotch's KT.
      CONCLUSIONS: EKRc can account for KR and provide guidelines for all types of
      dialysis treatments: as far as urea is concerned, dialysis adequacy should
      require EKRc > or = 11 ml/min. However, it is likely that EKRc > or = 9 ml/min
      could suffice for patients with a substantial residual renal function.

PMID- 8856215
TI  - Pharmacokinetics of antimicrobial agents in anuric patients during continuous
      venovenous haemofiltration.
AB  - BACKGROUND: The optimal drug dosing in anuric patients undergoing continuous
      haemofiltration is a difficult task. More pharmacokinetic data is needed to
      derive practical guidelines for dosage adjustments. METHODS: Drug elimination of
      various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin,
      flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin,
      sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute
      renal failure treated by pump-assisted continuous venovenous haemofiltration
      (CVVH). Concentrations of serial blood and ultrafiltrate samples were determined
      by HPLC or by fluorescence polarization immunoassay. Total body clearance (CL)
      and haemofilter clearance (CLf) rates were determined by standard model
      independent equations. Data from published literature on fractions not bound to
      proteins (fu), non-renal drug clearance fractions (Qo), and normal clearance
      values (CLn) were used to derive a pharmacokinetic model, taking into account
      drug removal by ultrafiltration and by non-renal clearance. RESULTS: A total of
      37 treatment periods was studied. Blood flow through the haemofilters was 100
      ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2 +/- 4.6
      (range 3.2-22.1) ml/min. Acceptable correlations of calculated and measured
      haemofilter clearances and total body clearances were obtained. CONCLUSIONS:
      Total body clearance in anuric patients during CVVH is predictable from drug
      properties, which are generally known. The individual dosage requirements may be
      calculated by multiplying Qo + fu.UFR/CLn with the dose considered appropriate in
      the absence of renal impairment.

PMID- 8856216
TI  - High-normal calcium (1.35 mmol/l) dialysate in patients on CAPD: efficient and
      safe long-term control of plasma calcium, phosphate, and parathyroid hormone.
AB  - AIM: The aim of the present study was to examine the long-term efficacy and
      safety of treatment with a high-normal calcium dialysate with a calcium
      concentration of 1.35 mmol/l in patients on CAPD. This dialysate calcium
      concentration is close to the high-normal plasma ionized calcium level aimed at
      in dialysis patients in order to suppress the parathyroid hormone secretion. The
      end-points of the study were (1) plasma ionized calcium (iCa) and phosphate (P)
      levels, (2) plasma intact parathyroid hormone (PTH) levels, (3) doses of calcium
      carbonate and alfacalcidol, (4) requirements of Al-containing phosphate binders,
      and (5) bone mineral density (BMD). RESULTS: Thirty-seven non-selected patients
      on CAPD treatment were followed for an average of 10 months after switching from
      a dialysate Ca of 1.75 to 1.35 mmol/l. After 1 week, a significant decrease of
      mean iCa from 1.26 +/- 0.01 to 1.23 +/- 0.01 mmol/l (P < 0.05) and an increase of
      median PTH from 80 to 135 pg/ml (P < 0.01) were seen. From the 2nd week and
      onwards, however, basal levels of iCa and PTH were restored and remained stable.
      mean plasma iCa was kept within 1.23-1.31 mmol/l; mean plasma P below 1.65 mmol/l
      and median PTH within 52-135 pg/ml. Episodes of hypercalcaemia were few (1.2
      cases of plasma iCa > 1.45 mmol/l per 100 treatment weeks), and the need for Al
      containing P binders low with only five patients requring this treatment for
      isolated and four patients for repeated episodes of hyperphosphataemia or
      hypercalcaemia. After switching from a dialysate Ca of 1.75 to 1.35 mmol/l, the
      doses of calcium carbonate and alfacalcidol could be significantly increased.
      Furthermore, using the dialysate Ca of 1.35 mmol/l made it possible to induce a
      controlled increase of PTH levels to 80-100 pg/ml by a temporarily
      discontinuation of alfacalcidol and/or a reduction of calcium carbonate dosage in
      the patients where PTH had become suppressed to levels below the upper normal
      limit. The intention of the treatment was to maintain PTH levels within 1.5-2.5
      times the upper normal limit for non-uraemic patients. Pre-study BMD of the
      vertebral bodies L2-L4 and of the femoral neck were normal and not significantly
      different from post-study measurements. CONCLUSION: The present study
      demonstrated that when using a high-normal dialysate Ca concentration of 1.35
      mmol/l in non-selected patients on CAPD treatment, high-normal plasma iCa and
      near-normal plasma P levels could be readily achieved with a minimal risk of
      incidental hypercalcaemia despite use of calcium carbonate as the main P binder.
      As a consequence of the tight Ca and P regulation, minimal doses of alfacalcidol
      were required to keep PTH within acceptable limits. We recommend this dialysate
      Ca concentration as a first-choice therapy for the majority of patients starting
      on CAPD treatment.

PMID- 8856217
TI  - Protein nitrogen appearance in CAPD patients: what is the best formula?
AB  - BACKGROUND: The protein equivalent of nitrogen appearance is an indirect index
      commonly used to assess dietary protein intake in patients on CAPD. Moreover it
      has been suggested that the ratio between nitrogen appearance and dietary
      nitrogen intake (fractional urea synthesis) can predict nitrogen balance in
      uraemic patients. Several formulae to directly calculate the protein equivalent
      of nitrogen appearance have been published. It has not been established, however,
      what formulae give the most appropriate estimate of protein intake and nitrogen
      appearance. STUDY DESIGN: Nitrogen balance studies were carried out in seven
      stable patients on CAPD. All of the patients were receiving a diet whose protein
      content (1.2 g/kg/body wt/day) and calorie content (35 kcal/kg/body wt/day) were
      rigorously controlled. Six formulae for calculating protein equivalent of
      nitrogen appearance and nitrogen appearance were tested and the agreement of the
      estimating formulae was evaluated by means of the Bland and Altman method.
      RESULT: Net nitrogen balance was 1.68 +/- 0.9 g/N day, protein intake (g/day) 81
      +/- 19, protein intake (g/kg) 1.05 +/- 0.17. Differences in protein equivalent of
      nitrogen appearance of up to about 20% were found. The smallest differences
      between protein equivalent of nitrogen appearance and protein intake were
      obtained by the formulae of Bergstrom (1 +/- 7 g, limits of agreement -12 and +15
      g) and Blumenkrantz (-2 +/- 5 g, limits of agreement -11 and +7 g). The formula
      of Bergstrom most closely estimated nitrogen appearance (-0.35 +/- 0.89 g). Using
      such formula, the fractional urea synthesis was 54 +/- 12%, giving evidence of
      positive nitrogen balances. CONCLUSION: For the routine monitoring of protein
      equivalent of nitrogen appearance in CAPD patients, we recommend Bergstrom's
      formula with the determination of dialysate protein losses.

PMID- 8856218
TI  - Do cyclosporin profiles provide useful information in the management of renal
      transplant recipients?
AB  - BACKGROUND: This study investigated the relationships between cyclosporin A (CsA)
      blood levels and episodes of renal allograft rejection and nephrotoxicity
      following renal transplantation, with the aim of establishing whether CsA
      profiles provided more useful information than single CsA blood levels in respect
      of these relationships. METHODS: One hundred and sixty-two profiles were
      performed over 16 months in 40 patients and analysed retrospectively. Blood
      samples were taken at 0, 2, 4, 6 and 8 h after the morning CsA dose. Rejection
      episodes were diagnosed by renal biopsy and CsA nephrotoxicity by a fall in serum
      creatinine 1 week after a cut in CsA dose. RESULTS: The mean area under the curve
      (AUC) was lower for profiles performed at the time of rejection (3821 h.ng/ml)
      than that of a matched group of non-rejecting profiles (5479 h.ng/ml; P < 0.02).
      An AUC above 6400 h.ng/ml significantly discriminated rejection from non
      rejection, whereas pre-dose and peak CsA concentrations did not have such
      discriminating cut-off values. A comparison of CsA-toxic and non-toxic profiles
      showed that there were no significant differences between mean CsA concentrations
      nor between the mean AUCs of these groups. CONCLUSION: We conclude that basing
      CsA dosing on CsA profiles could help to avoid some early episodes of rejection
      without increasing the risk of nephrotoxicity.

PMID- 8856219
TI  - Low prevalence of human papillomavirus infection of the cervix in renal
      transplant recipients.
AB  - BACKGROUND: An increased risk of anogenital tract malignancies has been noted
      among renal transplant recipients. A high prevalence of human papillomavirus
      (HPV) infection of the cervix in the female renal-transplant population has been
      assumed based on increasing evidence suggesting that HPV infection is the major
      risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. It
      has been assumed that immunosuppression leads to either a reactivation of latent
      HPV or a reduction in the host's ability to contain a primary HPV infection,
      thereby increasing the risk of CIN and cervical cancer. The objective of this
      study was to evaluate the prevalence of human papillomavirus (HPV) infection in a
      population of iatrogenically immunosuppressed renal transplant recipients.
      METHODS: Twenty-one women were recruited from the renal transplant clinic at
      Presbyterian Hospital and underwent a gynaecological examination which included
      colposcopy, a Papanicolaou smear, and a cervicovaginal lavage. Lavage samples
      were analysed for HPV DNA using L1 consensus primers and the polymerase chain
      reaction (PCR). RESULTS: No cases of cervical intraepithelial neoplasia (CIN)
      were detected in this cohort of 21 immuno-suppressed renal transplant recipients.
      HPV DNA was detected in only a single patient. CONCLUSIONS: Our data suggests
      that HPV infection is not highly prevalent among older, cytologically normal
      renal transplant recipients, particularly those who are currently monogamous or
      not presently sexually active. This study suggests that recent sexual behaviours
      are more important than past behaviours as a determinant of HPV status in
      transplant recipients, and also suggests that education concerning the avoidance
      of high-risk sexual behaviour is an important part of the care of the female
      renal transplant recipient. Our data is consistent with previous work suggesting
      that the incidence of CIN is declining in transplant recipients, and it also
      suggests that the prevalence of HPV infection may be declining as well.

PMID- 8856220
TI  - Cholesterol atheromatous embolism: an increasingly recognized cause of acute
      renal failure.
AB  - BACKGROUND: Cholesterol atheromatous embolism is a systemic disease resulting
      from cholesterol crystal embolization to many organs, including the kidney.
      Vascular surgery, vascular radiology investigations and anticoagulation have been
      identified as inciting factors. METHODS: Fifteen patients with extensive
      atherosclerosis, presenting with simultaneous occurrence of acute renal failure
      and peripheral ischaemic changes were diagnosed as having acute renal failure due
      to cholesterol atheromatous embolism. RESULTS: The patients, 12 men and three
      women, had an average age of 65 years. In one patient, spontaneous occurrence of
      the disease was observed. An inciting factor was identified in 14 patients:
      aortography in 10, aortic surgery in two, and thrombolysis in two. Clinical
      course of acute renal failure was quite variable. Four patients required
      dialysis; 11 were conservatively managed. All patients had concomitant skin
      lesions, including digital mottling, cyanosis and gangrene of the toes, and
      livedo reticularis of the lower limb and abdomen. Eosinophilia was the most
      common laboratory abnormality. The diagnosis of cholesterol atheromatous embolism
      was confirmed by tissue examination in eight; in three it was based on the
      finding of retinal cholesterol emboli; in four patients it was made on clinical
      grounds. Seven patients died within 36 months. Death was most commonly from
      cardiac causes. CONCLUSIONS: Since the population at risk for cholesterol
      embolism is growing and the disease is iatrogenic in origin, we should expect to
      detect cholesterol embolism with greater frequency as cause of acute renal
      failure in the future.

PMID- 8856221
TI  - Whole body and regional body composition in patients with chronic renal failure.
AB  - BACKGROUND: Nutritional state is a powerful prognostic factor in chronic renal
      failure (CRF). Techniques for the assessment of nutrition have limitations which
      are often most marked in the presence of renal disease. We have used techniques
      of body composition analysis to assess the nutritional state of groups of
      patients with CRF. METHODS: Body composition was measured in groups of patients
      with advanced CRF on conservative treatment, peritoneal dialysis, and
      haemodialysis and the results compared with a healthy control group. The
      selection criteria for the CRF patients ensured that they were "stable' with no
      recent intercurrent illness, and dialysis adequacy was satisfactory according to
      currently accepted targets. RESULTS: Whole body dual energy X-ray absorptiometry
      (DEXA) found significant reduction in lean tissue in haemodialysis patients and
      female peritoneal dialysis patients. Regional analysis with DEXA showed reduction
      in limb (especially arm), lean tissue in CRF patients, with arm lean tissue being
      reduced in all three CRF groups for females and both dialysis groups for males.
      Limb/trunk lean tissue ratios were significantly reduced for all CRF groups.
      Bioelectrical impedance showed reductions of fat-free mass in the same groups who
      had reduced whole body lean tissue with DEXA, but skinfold anthropometry failed
      to detect any significant reduction in fat-free mass. CONCLUSIONS: We conclude
      that even in "healthy' groups of CRF patients receiving adequate dialytic and
      dietary management, lean tissue depletion is a common problem. Regional analysis
      by DEXA, with measurement of limb lean tissue mass is a more sensitive method for
      the detection of lean tissue depletion than measurement of whole body lean tissue
      in patients with CRF.

PMID- 8856222
TI  - Immunotactoid glomerulopathy with extrarenal deposits in the bone, and chronic
      cholestatic liver disease.

PMID- 8856223
TI  - Membranous nephropathy associated with an inflammatory myelopathy.

PMID- 8856224
TI  - Intracardiac thrombus in an adult patient with nephrotic syndrome.

PMID- 8856225
TI  - Sarcoidosis and primary systemic vasculitis.

PMID- 8856226
TI  - A case of thyrotoxic hypokalaemic periodic paralysis in a Greek man.

PMID- 8856227
TI  - Intermittent ureteric obstruction caused by 'floating' renal transplant.

PMID- 8856228
TI  - Aspergillus infection of a renal allograft without evidence of a site of origin.

PMID- 8856229
TI  - Acute renal failure following ACE inhibition in a patient with coarctation of the
      aorta.

PMID- 8856230
TI  - The patient with chronic renal failure of unknown origin--don't forget Sjogren's
      syndrome.

PMID- 8856231
TI  - The erythrocyte cast.

PMID- 8856232
TI  - An acid-base conundrum for a rainy afternoon.

PMID- 8856233
TI  - Programme for harmonization of training in nephrology in the European Union.

PMID- 8856234
TI  - Adhesion molecules in rejection and tolerance of allografts.

PMID- 8856235
TI  - View from across the Atlantic. America struggles with health care reform.

PMID- 8856236
TI  - SLE; should a rise in dsDNA antibody be treated?

PMID- 8856237
TI  - Effects of angiotensin-receptor antagonists on erythrocytosis after renal
      transplantation.

PMID- 8856238
TI  - Brown tumours and secondary hyperparathyroidism--a continuing saga.

PMID- 8856239
TI  - Diabetic patients on renal replacement therapy.

PMID- 8856240
TI  - Usefulness and risk of erythropoietin therapy in pregnancies of patients with
      chronic renal insufficiency.

PMID- 8856241
TI  - Azathioprine-induced hepatic veno-occlusive disease in a renal transplant
      recipient: histological regression following azathioprine withdrawal.

PMID- 8856242
TI  - Outcome of acute renal failure in the elderly: a different approach.

PMID- 8856243
TI  - Role of cytokines and growth factors in glomerulonephritis: a chance for future
      therapeutic intervention.
AB  - Recent studies using experimental models of glomerular disease have not only
      elucidated the pathophysiologic basis of glomerular disease, but have also
      identified potential new treatments. In this review, we will provide examples of
      how cytokines and cytokine antagonists may be used in the future treatment of
      glomerular disease. Treatments will be presented for each of the pathophysiologic
      phases of disease, beginning with the etiology, the development of a
      nephritogenic immune response, the mechanisms by which glomerular injury occurs,
      the response of the glomerulus to injury that results in cell proliferation and
      matrix expansion, and the factors that lead to healing or scarring. Special
      emphasis is placed on the cytokines interleukin 1 beta and tumor necrosis factor
      alpha, which are proinflammatory cytokines that potentiate neutrophil- and
      monocyte-mediated glomerular injury, and on the growth factors platelet-derived
      growth factor and transforming growth factor beta, which are involved in cell
      proliferation and matrix expansion that occur as glomerular cells respond to
      injury. The identification of the specific mediators involved in glomerular
      disease should provide new therapies that are more specific and less toxic than
      current conventional immunosuppressive regimens.

PMID- 8856244
TI  - Heparins for proliferative nephritides? Short review on an advancing topic.
AB  - The rationale behind a proposed use of heparins for the control of proliferative
      nephritides is presented. Heparins stop adhesion of leucocytes to endothelial
      cells, they are anti-complementary, they modulate the activities of phagocytes
      and they stop the proliferation of mesangial cells or vascular smooth muscle
      cells. Heparins prevent the release of endothelin-1 and potentiate the action of
      constitutive nitric oxide. Low-molecular-weight heparins or pentosan polysulphate
      are now favoured.

PMID- 8856245
TI  - Diabetic renal failure and serum accumulation of the creatinine oxidative
      metabolites creatol and methylguanidine.
AB  - Diabetic patients (n = 23) with chronic renal failure (CRF) accumulate the
      creatinine (Cr) oxidative metabolites creatol (CTL) and methylguanidine (MG; a
      uremic toxin) in their sera. Analysis of serum CTL, a key intermediate in
      mammalian Cr catabolism into MG, is shown to offer some useful diagnostic
      information on CRF, especially in the determination of an initial stage of
      pathological renal failure. The sera of all diabetic (n = 23) and nondiabetic (n
      = 20) patients with CRF (s-Cr > 1.25 mg/dl) contained s-CTL (> 2 micrograms/dl),
      whereas those from normal subjects (n = 18) and diabetic patients (n = 18)
      without CRF contained no detectable s-CTL. A similar accumulation of s-MG was
      observed, but only when s-Cr was higher than 2.0 mg/dl. Although each s-CTL (Y:
      microgram/dl, Y': mol/l) and s-MG level (Z: microgram/dl, Z': mol/l) is highly
      correlated with s-Cr (X: mg/dl, X': mol/l) in a normal equation, Y or Z = AX + B,
      an alternative correlation in a second-order equation, Y or Z = alpha X2 + beta
      X, could also fit well. Since the quadratic equation can be convertible to Y/X or
      Z/X = alpha X + beta [Y'/X' or Z'/X' = alpha' X+ beta'] and active oxygen
      species, especially hydroxyl radicals, convert Cr into CTL, Y/X, Y'/X', Z/X and
      Z'/X' values which might be a kind of indices for oxygen stress (oxidative
      stress) increased in proportion to the increased severity of CRF in such
      patients. Although its meaning and interpretation are still debatable, diabetic
      CRF patients had a significantly higher alpha' value (2.2) than that (0.89) of
      nondiabetic CRF patients. All serum values for Cr, CTL and MG were measured with
      HPLC.

PMID- 8856246
TI  - Morphine modulates migration of monocytes.
AB  - Macrophages seem to play an important role in the development of
      glomerulosclerosis. In the present study we evaluated the effect of morphine, an
      active metabolite of heroin, on the migration of monocytes across a filter in a
      modified Boyden chamber. Morphine-mesangial cell interaction enhanced (p < 0.004)
      the migration of monocytes across the filter (control 14.2 +/- 0.6 vs. morphine
      22.1 +/- 1.7 monocytes/HPF). Dimethylthiourea (DMTU), a free radical scavenger,
      attenuated this effect of morphine. Morphine-monocyte secretory products (MMSP)
      did not modulate the migration of monocytes. However, the products of interaction
      between mesangial cells and MMSP enhanced (p < 0.001) the passage of monocytes
      across the filter. Mesangial cells treated with MMSP showed mRNA expression for
      monocyte chemoat-tractant peptide-1 (MCP-1). Superoxide also induced mRNA
      expression for MCP-1 on MC. DMTU attenuated this effect of superoxide. Since
      morphine activates MC to produce superoxide and DMTU attenuated the effect of
      superoxide on MC, the effect of morphine on the migration of macrophages may be
      mediated through superoxide-induced generation of MCP-1. We conclude that
      morphine enhances the migration of monocytes. This effect of morphine may be
      contributing to the development of glomerulosclerosis in patients with heroin
      addiction.

PMID- 8856247
TI  - The periodicity of vascular access thrombosis.
AB  - A periodicity has been observed in thrombotic events that occur in a variety of
      vascular beds. There also has been a recent suggestion that there is an increased
      failure of hemodialysis vascular accesses due to thrombosis during the summer
      months. We reviewed the last 949 episodes of vascular access thrombosis and found
      no seasonal pattern, but a weekly pattern was noted that corresponded to the
      patients' dialysis schedule. That pattern was apparently due to our technique of
      observation and not due to any intrinsic periodicity in the thrombosis itself. We
      find no evidence to support the belief in any intrinsic periodicity in
      hemodialysis vascular access thrombosis and since the thrombotic event itself is
      usually asymptomatic, any accurate assessment of a diurnal or circumseptan
      pattern is not possible under ordinary clinical conditions.

PMID- 8856248
TI  - An analysis of monocyte/macrophage subsets and granulocyte-macrophage colony
      stimulating factor expression in renal allograft biopsies.
AB  - The role of infiltrating macrophages in the pathogenesis of acute rejection was
      investigated in biopsy specimens obtained from human transplanted kidneys using
      immunohistochemical methods. Thirty-one allograft tissue specimens obtained from
      26 patients were histologically classified into 18 with acute rejection, 7 with
      borderline change and 6 with chronic rejection according to the Banff working
      classification (1993). These specimens were analyzed by avidin-biotin peroxidase
      complex method on frozen sections in order to examine the utility of some
      antimonocyte/macrophage monoclonal antibodies in differentiating acute rejection
      from other conditions. The ratio of CD68, CD11b, LeuM3, OKM5 and HAM56-positive
      infiltrating monocytes/macrophages to leukocyte common antigen (LCA)-positive
      cells in the renal cortex were calculated. As a result, the ratio of the positive
      cells for CD68, which stains mature macrophages, significantly increased in the
      cases of acute rejection compared with those of other groups. In addition, a
      strong expression of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      was observed in the acute rejection group. In our study, the expression of class
      II major histocompatibility antigens (HLA-DR) in the proximal epithelial tubules
      was also strongly observed in the cases of acute rejection. It was thus concluded
      that the increase of CD68-positive infiltrating cells and the expression of GM
      CSF may play a possible role as a reaction effector in the process of acute renal
      allograft rejection.

PMID- 8856249
TI  - Laser Doppler flowmeter assessment of skin microcirculation in uremic patients on
      hemodialysis treatment.
AB  - Vascular disease is frequent in uremics and may contribute to tissue malnutrition
      and damage. The aim of this study was to detect whether uremic patients show also
      changes of microcirculation and to evaluate the effects induced by hemodialysis
      (HD) session. Eleven uremics on HD (7 males, 4 females, aged 25-65 years) were
      studied; 11 healthy subjects, age- and sex-matched, served as controls. Skin
      microcirculatory basal flow (BF), maximal postischemic flow (PIF-max) and flow
      motion index (FMI) were determined at the upper limb contralateral to
      arteriovenous fistula, by means of a laser Doppler flowmeter. The measurements
      were taken before, at 1 and 2 h after starting HD and 30 min after the end of HD.
      In uremics, FMI was lower than in controls (mean +/- SD: 15.2 +/- 13.6 vs. 29.1
      +/- 7.4%; p < 0.005); just 1 h after the start of HD, a significant improvement
      (28.4 +/- 17.7%; p < 0.01) versus basal values was observed and it persisted
      throughout the HD session. No statistical correlation was observed between the
      changes of FMI and those of plasma levels of Na+, K+, HCO-3, urea, iPTH or rate
      of ultrafiltration. BF and PIF-max were similar in uremics and controls, and no
      changes were observed during HD. Our study shows that the physiological flow
      motion is reduced in the skin microcirculation of uremics on HD. This abnormality
      is rapidly corrected by HD.

PMID- 8856250
TI  - Angiography with nonionic X-ray contrast media in severe chronic renal failure:
      renal function and contrast retention.
AB  - The effects of contrast media on renal function and the cortical retention of
      contrast media after abdominal angiography were investigated. Sixteen nondiabetic
      patients with predialytic chronic renal failure received either the nonionic
      dimeric contrast medium iodixanol or the monomeric contrast medium iohexol in a
      double-blind randomized study. All patients were well hydrated before, during and
      after angiography. Mean 99mTc-DTPA clearance was 14.0 ml/min/1.73 m2 in the
      iodixanol group, and 9.3 ml/min/1.73 m2 in the iohexol group at baseline. No
      statistically significant changes were seen after angiography. Serum creatinine
      increased significantly 48 and 72 h after angiography in both groups, and then
      normalized. Creatinine clearance was reduced only in the iohexol group, at 72-96
      h. The urinary excretion of renal enzymes and of total protein did not change
      significantly. No patients developed oliguria or required dialysis during the 7
      day observation period. Increased attenuation in the renal cortex, measured by
      computed tomography and probably reflecting intracellular retention of contrast
      medium, peaked at 24 h, and was observed in both groups during the follow-up
      period. Thus, although transient and minor changes in glomerular filtration rate
      were noted, both iodixanol and iohexol were safe for use in angiography in
      nondiabetic patients with severe chronic failure when the patients were well
      hydrated.

PMID- 8856251
TI  - Bone mineral density in patients with hypercalciuric nephrolithiasis.
AB  - Bone mineral density was studied in 50 adult patients with renal lithiasis and
      metabolic diagnosis of idiopathic hypercalciuria. Thirty were premenopausal women
      and 20 were men under 55 years of age, Bone density at the lumbar spine (LSBD)
      was 0.940 +/- 0.106 g/cm2 in the hypercalciuric patients compared to 1.112 +/-
      0.037 g/cm2 in a cohort of age- and sex-matched controls (p < 0.001). LSBD was
      independent of age and was negatively correlated with the duration of stone
      disease (r = -0.52, p < 0.001). Thus we conclude that patients with idiopathic
      hypercalciuria have a decrease in their LSBD that is probably related to a
      negative calcium balance sustained over time.

PMID- 8856252
TI  - Study of the effects of different substances on the early stages of papillary
      stone formation.
AB  - We have studied the early stages of calcium oxalate monohydrate (COM)
      crystallization, mainly heterogeneous nucleation, on fixed particles. Experiments
      were performed using a flow system that closely simulates the human renal
      conditions related to COM heterogeneous nucleation. The effects of citrate,
      phytate, aescin and glycyrrhinic acid in the COM heterogeneous nucleation on
      different solid surfaces as calcium phosphate, a mixture of mucin and calcium
      phosphate and wax were studied. The presence of citrate at normal urinary
      concentrations (1.85.10(-3) M) totally inhibited the development of COM crystals
      only on the most hydrophobic assayed material (wax). Saponins (aescin and
      glycyrrhinic acid) only exhibited important inhibitory effects of COM
      crystallization on the hydrophobic wax substrate but in no case the formation of
      COM crystals was totally prevented. Phytate exerted the most remarkable effects
      on the heterogeneous nucleation of COM crystals, thus, when it was present at
      1.43.10(-7) M, it totally prevented the development of COM crystals on the three
      assayed solid substrates.

PMID- 8856253
TI  - Hypertension in kidney stone patients.
AB  - The prevalence of arterial hypertension (HT) was investigated in 258 patients
      (171 m, 87 f, 22-68 years) with a history of primary stone disease. HT was
      detected in 64 patients (24.8%), with no difference between males (25.7%) and
      females (23.0%). The prevalence of HT by age was very similar to that of a
      general population, especially in the calcium stone group. The discriminant
      analysis demonstrated that the composition of stones, other than the age and body
      weight of the patients, were the main factors associated with HT. As far as the
      different kind of stone is concerned, the prevalence of HT was higher in patients
      with uric acid (17/37, 45.9%) and struvite stones (11/27, 40.7%) than in calcium
      stone formers (35/188, 18.6%) (chi 2 16.31, p < 0.001). The prevalence of
      hypercalciuria was higher in the calcium stone group than in uric acid or
      struvite stone patients (36.4 vs. 9.7 vs. 13.7%; chi 2 10.35, p < 0.01).
      Furthermore, the hypercalciuria showed a trend to be more prevalent in the
      untreated (47.0%) than in the treated (31.2%) hypertensives, or normotensives
      (35.1%). Uric acid stone formers were older, heavier and with higher
      triglycerides and uric acid plasma levels than calcium or struvite patients. Also
      the struvite stone formers were older than the calcium stone ones. Our data
      suggest that the prevalence of HT in kidney stone patients and particularly in
      calcium stone formers is similar to that of a general population. The role of
      hypercalciuria as the link for HT-urolithiasis association seems quite uncertain.
      Struvite and uric acid stone formers have higher risk for HT than calcium stone
      formers, probably due to the old age or to the associated metabolic
      abnormalities.

PMID- 8856254
TI  - The changes of Mac-1 and L-selectin expression on granulocytes and soluble L
      selectin level during hemodialysis.
AB  - L-selectin and Mac-1 expressed on leukocytes are critical for leukocyte adhesion
      to inflamed endothelium. L-selectin is known to be rapidly shed from the cell
      surface of granulocytes after activation. In the present study the change of
      expressions of these adhesion molecules on granulocytes were analyzed by flow
      cytometry, and the serum concentration of shed L-selectin (soluble L-selectin; sL
      selectin) was measured by enzyme-linked immunosorbent assay (ELISA) during
      hemodialysis in patients treated with regenerated cellulose membranes (RC group)
      versus polysulfone membranes (PS group). In the RC group, Mac-1 expression on
      granulocytes increased significantly at 30 min after the initiation of
      hemodialysis (p < 0.05) compared with predialysis values, coinciding with the
      nadir of dialysis-induced granulocytopenia. Granulocyte L-selectin expression
      decreased significantly at 15 min after the initiation of hemodialysis (p < 0.05)
      and remained decreased through the course of dialysis session, compared with
      predialysis values. Serum sL-selectin level significantly increased at 15 min
      after the initiation of hemodialysis (p < 0.05), compared with predialysis
      values. In the PS group, no significant variation in Mac-1 and L-selectin
      expression on granulocytes and serum sL-selectin level were detected. This
      reciprocal change of Mac-1 and L-selectin on granulocyte cell surface was
      attributed to development of granulocytopenia and subsequent reversal during
      dialysis with cellulose membranes. In this study, we confirmed the shedding of L
      selectin during cellulosic dialysis by ELISA. The increase in sL-selectin, which
      has potential activity of inhibiting L-selectin-dependent adhesion of granulocyte
      to endothelium, might be involved in rebound granulocytosis during dialysis with
      cellulose membranes and impairment of the granulocyte function in patients on
      chronic hemodialysis.

PMID- 8856255
TI  - Oxyphil cell function in secondary parathyroid hyperplasia.
AB  - Oxyphil cell function in secondary parathyroid hyperplasia due to chronic renal
      failure was evaluated using in situ hybridization and heterotransplantation of
      parathyroid tissue. In situ hybridization and histologic analysis were performed
      on continuous frozen sections using 22 parathyroid tissues. A restricted area
      composed exclusively of oxyphil cells was observed in 10 specimens, and an area
      of only chief cells was found in 12 specimens. Silver grains demonstrating the
      existence of parathyroid hormone (PTH) mRNA were 18.8 +/- 7.8 (mean +/- SD) in
      oxyphil cells while those in chief cells were 17.2 +/- 7.5. PTH mRNA was abundant
      in both the oxyphil and chief cells. Further analysis of oxyphil cell function
      was assessed by the heterotransplantation of parathyroid nodules, consisting
      exclusively of oxyphil or chief cells, into nude mice. The function of these
      implants was assessed by measuring the concentration of human intact PTH which
      did not cross-react with mouse PTH. Serum PTH concentrations were correlated with
      the volume of implanted tissue. Elevations of PTH concentrations were similar in
      the mice transplanted with oxyphil or chief cells, indicating that both cell
      types had similar PTH secretory activity. The basic histologic characteristics of
      both cell types were not altered following transplantation. These results
      demonstrate that oxyphil cells in secondary parathyroid hyperplasia synthesize
      and secrete PTH, and that this secretion contributes to the pathophysiology of
      hyperparathyroidism.

PMID- 8856256
TI  - Escherichia coli-macrophage interactions modulate mesangial cell proliferation
      and matrix synthesis.
AB  - Patients with chronic renal interstitital diseases often develop glomerular
      lesions (focal segmental glomerular sclerosis). Because mesangial expansion
      (enhanced mesangial cell (MC) growth and matrix accumulation) has been
      demonstrated to precede the development of focal segmental glomerulosclerosis, we
      studied the effect of the interaction between bacteria such as Escherichia coli
      and macrophages on MC proliferation and matrix synthesis. We determined the
      effect of control media (CM), E. coli supernatant (ESP), serum-free macrophage
      supernatant (MSP), and E. coli-treated macrophage supernatants (HB101-MSP, H10
      MSP) on the proliferation of MCs and synthesis of laminin (a component of
      mesangial matrix). ESP did not alter MC growth, whereas E. coli MSP increased the
      mean MC number by 5- to 6-fold when compared to cells treated with CM. Both HB101
      MSP and H10-MSP stimulated greater (p < 0.05) incorporation of [3H]thymidine when
      compared with MSP (HB101-MSP 3.1 +/- 0.4, H10-MSP 2.7 +/- 0.3 vs. MSP 1.6 +/- 0.2
      x 10(6) cpm/micrograms protein). When MC proliferation was judged by
      incorporation of bromodeoxyuridine, both HB101-MSP- and H10-MSP-treated cells
      showed a greater (p < 0.01) number of proliferating cells compared with cells
      treated with either MSP or CM. MC treated with H10-MSP grew in a specific pattern
      and showed a tendency to form hillocks (foci of cell proliferation and matrix
      aggregation). Both HB101-MSP and H10-MSP enhanced (p < 0.01) synthesis of laminin
      compared with CM. HB101-MSP-induced enhanced laminin synthesis was attenuated
      when MCs were treated with anti-transforming growth factor (TGF)-beta antibodies.
      HB101-MSP also increased mRNA expression of TGF-beta by MCs. These results
      indicate that E. coli-macrophage interaction has the potential to cause mesangial
      expansion.

PMID- 8856257
TI  - Quenching the thirst in dialysis patients.
AB  - In a double-blind cross-over trial, 22 stable end-stage renal failure patients on
      maintenance haemodialysis were subjected to conventional dialysis with dialysate
      containing 137 mEq/l sodium and constant ultrafiltration (UF) and to a different
      dialysis therapy, in which, by linear sodium modelling, the dialysate sodium was
      reduced from 137 to 128 mEq/l. A computerized UF program was used to gradually
      reduce the UF to a minimum towards the end of the session. Severity of thirst,
      interdialytic weight gain and intradialytic complications were less with low
      sodium dialysate. It allowed adequate UF with absolute hemodynamic stability. The
      reduced incidence of complication with low sodium dialysate therapy was probably
      because they required less UF.

PMID- 8856258
TI  - Difference of serum levels of type IV collagen 7S between early or overt
      nephropathy and nondiabetic renal disease in diabetic patients with micro- or
      macroalbuminuria.
AB  - We determined serum levels of type IV collagen 7S (IV 7S) in 73 (23 with
      normoalbuminuria, 21 with microalbuminuria, 17 with macroalbuminuria, and 12
      primarily affected by nondiabetic renal disease (NDRD)) and 24 (10 with only
      macroangiopathy and 14 with retinopathy and macroangiopathy) diabetic patients to
      see whether IV 7S can be a useful index for differentiating early or overt
      diabetic nephropathy from NDRD in micro- or macroalbuminuric diabetics. IV 7S was
      significantly elevated in diabetic patients with micro-or macroalbuminuria
      compared to those with normoalbuminuria and healthy controls (p < 0.001). On the
      contrary, all 12 diabetic patients with micro- or macroalbuminuria due to NDRD
      showed normal or low IV 7S level. IV 7S was significantly higher in diabetic
      patients with both retinopathy and macroangiopathy than in those with only
      macroangiopathy (p < 0.001). We conclude that IV 7S levels may be a useful index
      to differentiate diabetic early or overt nephropathy from NDRD, especially
      nephrosclerosis, in micro- or macroalbuminuric diabetics.

PMID- 8856259
TI  - Lipoprotein derangement during steroid treatment in minimal-change nephrotic
      syndrome.
AB  - To study the pathophysiology of hyperlipidemia in nephrotic syndrome, we compared
      lipid metabolism in the nephrotic stage (stage 1) and in stage 2, when
      albuminuria had subsided, in 11 patients with minimal-change disease treated with
      corticosteroid. High-density lipoprotein (HDL) levels were decreased and HDL
      contained more cholesterol and triglyceride per unit of protein in stage 1 in the
      patients than in age-matched healthy controls. The urinary protein level was
      positively correlated only with low-density lipoprotein (LDL) levels, suggesting
      that the increased albumin clearance stimulated LDL production. Serum cholesterol
      levels were positively correlated with apolipoprotein E levels and were
      negatively correlated with lecithin-cholesterol acyltransferase activity in the
      nephrotic stage; the opposite correlations were seen in controls. Although
      triglycerides in HDL had normalized at stage 2, triglycerides in LDL and very-low
      density lipoprotein did not return toward normal until stage 3, when serum
      cholesterol levels were normalized.

PMID- 8856260
TI  - Measures of tubular function in normoalbuminuric insulin-dependent diabetic
      patients and their relationship with sodium lithium countertransport activity.
AB  - The aim of this study was to assess the relationship between markers of tubular
      function, markers of glycaemic control and erythrocyte sodium-lithium
      countertransport activity (SLC) in 40 normotensive, normoalbuminuric insulin
      dependent diabetic (IDDM) subjects and 11 normal control subjects. Nine IDDM
      subjects had SLC > 0.40 mmol lithium h-1 litre RBC-1. Glomerular filtration rate
      (GFR) and the excretion rate of retinol-binding protein (RBP), N-acetyl-beta-D
      glucosaminidase (beta-NAG) and glucose were significantly higher in IDDM subjects
      compared to control subjects (Mann-Whitney test, p = 0.02, < 0.001, < 0.001 and <
      0.001, respectively), whilst the two groups had similar SLC and TmPO4 levels.
      There was no significant relationship between SLC and the other variables in IDDM
      subjects, even when comparing IDDM subjects with normal and high SLC. beta-NAG
      excretion rate was correlated to urinary glucose (rs 0.47, p = 0.001) and,
      weakly, to the other markers of glycaemic control (fasting blood glucose rs =
      0.31, p = 0.03, fructosamine rs 0.28, p = 0.04, HbA1 rs 0.27, p = 0.04). RBP
      excretion rate was correlated to the excretion rate of beta-NAG (rs 0.38; p =
      0.007) and albumin (rs 0.45; p = 0.002); the excretion rates of beta-NAG and
      albumin were significantly associated (rs 0.37, p = 0.009). Diabetes duration did
      not correlate to any of the aforementioned variables. In this study, beta-NAG and
      RBP overnight excretion rates were higher in normoalbuminuric IDDM subjects
      compared to control subjects but no relationship was present between SLC and
      tubular function in IDDM patients without complications. Excretion rates of
      different proteins appear to be interrelated and, in IDDM, beta-NAG excretion is
      associated with glycaemic control.

PMID- 8856261
TI  - Abnormal expression and regulation of vitamin D receptor in experimental uremia.
AB  - The low concentration of the biologically active metabolite of vitamin D, namely
      1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), is critical to the pathogenesis of
      secondary hyperparathyroidism in chronic renal failure. The actions of
      1,25(OH)2D3 are mediated through binding to a cellular receptor protein, the
      vitamin D receptor (VDR). In order to further investigate expression and
      regulation of VDR in uremia, we measured specific [3H]-1,25(OH)2D3 binding
      capacity and VDR mRNA concentration in intestinal mucosa and in parathyroid
      glands of subtotally nephrectomized rats (Nx) and compared Nx to sham-operated
      rats with normal kidney function (Intact). Intestinal [3H]-1,25(OH)2D3 binding
      capacity in short-term Nx (6-10 days after nephrectomy) was 663 +/- 114 fmol/mg
      protein; it was 517 +/- 34 in Intact (p = 0.06, n = 6 experiments). Intestinal
      VDR mRNA concentration was comparable between Nx and Intact. Specific 1,25(OH)2D3
      binding capacity in parathyroid glands was higher in Nx (195 +/- 9 fmol/mg
      protein) than in Intact (116 +/- 14 fmol/mg protein, n = 5, p < 0.05). The
      affinity of the VDR for 1,25(OH)2D3 (KD) did not change in Nx. The 1,25(OH)2D3
      binding capacity in intestinal mucosa of more long-term uremic animals (14-16
      weeks after subtotal Nx) was 519 +/- 32 fmol/mg protein versus 349 +/- 31 in
      Intact (n = 3, p < 0.01). Parathyroid VDR was 171 +/- 9 fmol/mg protein in long
      term Nx and 125 +/- 3 in Intact (p < 0.01). These results were confirmed when
      1,25(OH)2D3 binding capacity in uremic rats with hereditary polycystic kidney
      disease was compared to control rats with normal kidney function (757 +/- 54
      fmol/mg protein versus 495 +/- 59 in intestinal mucosa, p < 0.05; 273 +/- 48
      versus 104 +/- 27 in parathyroid glands, p < 0.05). In parallel to changes in
      intestinal 1,25(OH)2D3 binding capacity, 1,25(OH)2D3-mediated stimulation of
      intestinal 25(OH)D3-24-hydroxylase activity was significantly higher in long-term
      subtotally Nx (1.43 +/- 0.06 pmol 24,25-dihydroxyvitamin D3/mg protein) than in
      sham-operated normal rats (1.04 +/- 0.10, p < 0.05). Administration of
      1,25(OH)2D3 to sham-operated normal rats resulted in an increase of 1,25(OH)2D3
      binding capacity by 20-40% in intestinal mucosa and by 40-50% in parathyroid
      glands. In contrast, 1,25(OH)2D3 caused down-regulation of mean 1,25(OH)2D3
      binding capacity in short-term Nx by 38% in intestinal mucosa (p < 0.01) and by
      43% in parathyroid glands (p < 0.01). In long-term Nx, mean 1,25(OH)2D3 binding
      capacity was reduced by 20% in intestinal mucosa (p < 0.05) and by 22% in
      parathyroid glands (p < 0.01). After prolonged exposure to 1,25(OH)2D3 for 6
      weeks, intestinal 1,25(OH)2D3 binding capacity was markedly down-regulated in
      uremic rats (43% versus vehicle-treated animals p < 0.05). Taken together, our
      results provide evidence for abnormal expression and regulation of VDR in
      experimental uremia. This may be relevant for responsiveness to 1,25(OH)2D3 in
      renal insufficiency.

PMID- 8856262
TI  - Effect of a nonpeptide vasopressin V1 antagonist (OPC-21268) on experimental
      accelerated focal glomerulosclerosis.
AB  - The effects of the nonpeptide orally effective vasopressin V1 receptor antagonist
      OPC-21268 were studied in progressive focal glomerulosclerosis (FGS) which
      developed in spontaneously hypercholesterolemic (SHC) rats with manifestations of
      hypercholesterolemia and proteinuria. Unilateral nephrectomy was performed at 7
      weeks of age to accelerate spontaneous FGS. After nephrectomy, OPC-administered
      rats were fed chow containing 1% OPC-21268 for 9 weeks. Treatment with
      vasopressin V1 antagonist significantly reduced the rate of increase in the
      levels of triglyceride, systolic blood pressure, serum creatinine and BUN, and
      prevented a significant deterioration in creatinine clearance. Rats were
      sacrificed at 16 weeks of age. Histologically, the index of glomerular sclerosis
      in the OPC group showed a significant decrease compared to that in the control
      group (2.2 +/- 0.1 vs. 2.6 +/- 0.1, p < 0.01). Relative interstitial volume and
      glomerular volume in the OPC group showed a tendency to decrease compared to
      those in the control group. These results indicate that vasopressin plays an
      important role through V1 receptors in the development of glomerulosclerosis, and
      vasopressin V1 antagonist may prevent the progression of renal injury in
      glomerulosclerosis.

PMID- 8856263
TI  - Effects of the PGI2 analog beraprost sodium on glomerular prostanoid synthesis in
      rats with streptozotocin-induced diabetes.
AB  - A study of albuminuria, creatinine clearance (CCr) and blood pressure of
      streptozotocin (STZ)-induced diabetic rats with or without treatment by a
      prostacyclin (PGI2) analog, beraprost sodium (BPS), is described. Glomerular
      prostanoid synthesis was measured by gas chromatography (GC) mass spectrometry.
      Renal specimens stained with hematoxylin and eosin and periodic acid-Schiff were
      examined by light microscopy. Mean values of albuminuria in BPS-treated diabetic
      rats were significantly decreased compared with those in nontreated diabetic
      rats. The ratio of kidney to body weight in the BPS-treated diabetic rats was
      significantly lower than that in the nontreated diabetic rats. Levels of CCr and
      blood pressure were decreased in diabetic rats after the treatment with BPS. GC
      mass spectrometry showed that BPS did not influence the glomerular synthesis of
      PGI2 and TXB2. No histologic injury in the renal tissues was observed in the
      diabetic rats with or without BPS treatment. We concluded that BPS (PGI2 analog)
      might decrease the levels of urinary albumin excretion and CCr due to its
      vasodilating effects in the early phase of STZ-induced diabetes in rats.

PMID- 8856264
TI  - Recovery from ischemic acute renal failure: independence from dialysis membrane
      type.
AB  - Exposure to complement-activating cellulosic dialysis membranes has been claimed
      to adversely affect the course of acute renal failure. To test this hypothesis,
      male Sprague-Dawley rats were allocated to two groups: in group I, acute renal
      failure was induced by bilateral renal artery clamping, while group II animals
      underwent a sham procedure. In each group, the rats were further allocated to
      undergo hemodialysis with either a Cuprophan, a Hemophan, or a PAN miniDialyzer
      membrane 3 and 7 days after surgery or no dialysis. The renal function was
      measured by inulin clearance on the days following dialysis. Temporary occlusion
      of the renal arteries led to a rapid increase in serum urea and creatinine levels
      that peaked between 24 and 48 h after surgery and declined slowly thereafter.
      Peak urea values were similar in the acute renal failure groups. The hemodialysis
      sessions were well tolerated. Degree and rate of recovery were similar in all
      acute renal failure groups irrespective of whether they underwent dialysis or not
      or the type of the dialysis membrane. Complete recovery was observed in all the
      acute renal failure groups by the end of the observation period. Our findings
      refute the hypothesis that in ischemic acute renal failure exposure to complement
      activating cellulosic dialysis membranes impairs the recovery of renal function.

PMID- 8856265
TI  - Cytochrome P450 4A expression and arachidonic acid omega-hydroxylation in the
      kidney of the spontaneously hypertensive rat.
AB  - 20-Hydroxyeicosatetraenoic acid (20-HETE) is a major arachidonate metabolite in
      the kidney of the spontaneously hypertensive rat (SHR). The increase in its
      synthesis has been associated with the elevation of blood pressure in the SHR.
      The omega-hydroxylation of arachidonic acid is an activity associated with
      members of the CYP4A gene family which, in the rat, comprises three major
      isoforms: 4A1, 4A2 and 4A3. 20-HETE displays potent and diverse biological
      activities which can affect pro- and anti-hypertensive mechanisms dependent upon
      where, when and by which isoform it has been produced. Therefore, it is important
      to identify and characterize its biosynthetic system. We compared CYP4A mRNA and
      protein expression to patterns of 20-HETE synthesis in the SHR kidney. The
      reverse transcription/polymerase chain reaction (RT/PCR) technique was used to
      amplify CYP4A mRNA in microdissected nephron segments. Southern blot
      hybridization of PCR products obtained from nephron segments with the CYP4A1 cDNA
      probe demonstrated strong signals in S2 and S3 segments of the proximal tubule.
      Immunoblots of nephron segments using a polyclonal anti-rat liver CYP4A1 antibody
      which cross-reacts with CYP4A2 and CYP4A3, and 14C-arachidonic acid metabolism,
      confirmed that arachidonic acid omega-hydroxylation, i.e., 14C-20HETE formation,
      and CYP4A proteins were also localized mainly in the S2 and S3 segments.
      Correlation also existed between the age-dependent increase in arachidonate omega
      hydroxylation in the kidney and CYP4A mRNA levels as measured by Northern
      hybridization of total RNA using the CYP4A1 cDNA probe. Immunoblot analysis
      revealed that at 7 weeks, where 20-HETE production is at its maximum, all three
      proteins are expressed. CYP4A3 and 4A1 immunoreactive proteins appeared at 3
      weeks, showed maximum levels at 5 and 7 weeks, respectively, and gradually
      decreased to lower levels at 13 and 20 weeks, whereas CYP4A2 levels were
      undetectable at 3, 5 and 7 weeks but appeared at 13-20 weeks. Additional
      immunoblots indicated that renal cortical CYP4A1 protein levels were higher in
      SHR compared to Sprague-Dawley and Wistar-Kyoto rats. The increased levels of
      CYP4A1-immunoreactive band at 7 weeks corresponded to the maximal activity of
      arachidonate omega-hydroxylation. Thus, CYP4A1 might play a significant role in
      contributing to the increased cortical/proximal production of 20-HETE seen in 7
      week-old SHR. However, given the high homology among members of the CYP4A gene
      family and the lack of specific tools to discern among these isoforms, additional
      studies have to be carried out to substantiate our findings.

PMID- 8856266
TI  - Sex chromosomes do not influence renal injury in borderline hypertensive rats.
AB  - The present study was undertaken to investigate whether the development of
      proteinuria in the borderline hypertensive rat (BHR) is influenced by the Y
      chromosome and to determine if the onset of proteinuria in the BHR is delayed
      when blood pressure is lowered with enalapril, an angiotensin I converting enzyme
      inhibitor. Male F1, rats were the first-generation offspring of the mating of
      spontaneously hypertensive (SHR) females and Wistar-Kyoto (WKY) males and the
      mating of SHR males and WKY females. At 20 weeks of age, enalapril (125 mg/l) was
      added to the drinking water. Untreated BHR and enalapril-treated BHR (BHRE) were
      followed to 90-100 weeks of age. Urine was collected every 10-20 weeks for
      determination of protein, albumin, and nitric oxide (NO2/NO3) metabolite
      excretion. Indirect blood pressure in BHR from both crosses was approximately 175
      mm Hg from 20 to 90-100 weeks of age. Enalapril lowered blood pressure by about
      30 mm Hg, but was ineffective in reducing urinary protein or albumin excretion
      rates at any age. Urinary excretion of nitric oxide metabolites was similar in
      all groups at all time periods. There were significant differences in the percent
      of glomerulosclerosis between the two matings. Based on these results, renal
      injury in the BHR is not associated with the Y chromosome and can be dissociated
      from hypertension. Further studies using congenic and transgenic technology will
      be necessary to identify functions of genes and associations with hypertension in
      order to understand the kidney disease in this model of hypertension.

PMID- 8856267
TI  - Minimal change glomerulonephritis in a 90-year-old patient: what is the ideal
      approach?
AB  - We report the case of a 90-year-old lady who presented with full-blown nephrotic
      syndrome. Percutaneous renal biopsy allowed us to confirm the diagnosis of
      minimal change glomerulopathy; she entered a 2-year period of remission after a 6
      month course of prednisone (starting dose 1.5 mg/kg). The patient sustained minor
      effects of both renal biopsy and corticotherapy. Percutaneous renal biopsy is
      justified in the very elderly because the risk of mortality and morbidity related
      to corticotherapy outweigh the risk related to percutaneous renal biopsy,
      providing high-risk patients are excluded, such as amyloidosis or abnormal
      coagulation or uncontrolled arterial hypertension.

PMID- 8856269
TI  - Renal wedge-shaped lesions on computed tomography and ultrasonography in two
      patients who developed acute renal failure with severe loin pain after exercise.
AB  - Acute renal failure (ARF) with loin pain after exercise with development of wedge
      shaped contrast enhancement on computed tomography (CT) has been described as a
      new disease entity. We report 2 patients who developed ARF with severe loin pain
      after exercise, showing wedge-shaped lesions both on CT and ultrasonography.
      Renal ultrasonography showed indistinct wedge-shaped lesions when performed at
      oliguric or recovery phase of ARF, whereas it showed distinct lesions when done
      between these two phases. Contrast CT performed at the recovery phase disclosed
      distinct wedge-shaped lesions. Our findings suggested that the best time to
      detect these lesions by ultrasonography is between at the beginning of diuresis
      and at the time of serum creatinine levels of 2 mg/dl.

PMID- 8856268
TI  - Hypophosphatemia in end stage renal disease.
AB  - A case of hypophosphatemia in a 55-year-old black female on maintenance
      hemodialysis is described. She developed multiple bone fractures and congestive
      heart failure during her 10-year period on hemodialysis. Iliac crest bone biopsy
      revealed osteomalacia with absent aluminium stores. Management was difficult due
      to her noncompliance secondary to severe depression. Though osteomalacia and
      cardiomyopathy due to hypophosphatemia are described in patients with end stage
      renal disease on dialysis, it is an uncommon entity.

PMID- 8856270
TI  - Pyomyositis in a renal transplant patient with Kyrle's disease.
AB  - Pyomyositis, an endemic disease of tropical origin, is increasingly reported in
      temperate zones, especially in patients with diabetes mellitus and in the
      immunocompromised. A 28-year-old renal transplant recipient presented with
      perforating skin lesions (Kyrle's disease), thigh pain, and swelling associated
      with fever. A gallium scan of the thigh led to surgical exploration and a
      diagnosis of pyomyositis. To our knowledge, the association of Kyrle's disease
      with pyomyositis has not been reported before. The significance of this
      combination of conditions in our patient remains unexplained.

PMID- 8856271
TI  - A case of nephrotic syndrome developing during postoperative gamma interferon
      therapy for renal cell carcinoma.
AB  - A 70-year-old man developed minimal-change nephrotic syndrome and acute
      interstitial nephritis while undergoing gamma interferon therapy following right
      nephrectomy for renal cell carcinoma. It appears that gamma interferon as well as
      renal cell carcinoma may have played a role as etiologic factors in this
      nephropathy. We report this extremely rare case of renal cell carcinoma
      complicated by minimal-change nephrotic syndrome and acute interstitial
      nephritis, and present a review of the literature.

PMID- 8856272
TI  - Renal involvement in Behcet's disease. Case report and review of the literature.
AB  - A female patient has suffered from Behcet's disease (BD) for 15 years. During one
      recurrent episode proteinuria and microscopic hematuria were discovered. Renal
      biopsy revealed focal segmental glomerulopathy with IgA deposits. Renal
      involvement in BD is uncommon and includes amyloidosis, crescentic
      glomerulonephritis and IgA nephropathy. BD is a cause of secondary IgA
      nephropathy. Immunologic features of the two diseases, particularly increased
      serum IgA, are reviewed.

PMID- 8856273
TI  - Membranous nephropathy complicating adenolymphoma of the parotid (Warthin's
      tumour).
AB  - Membranous nephropathy has been described in association with many malignancies
      including various lymphomas. However, it has not been previously described as a
      complication of benign solid adenolymphoma of the parotid, also called Warthin's
      tumour. We describe a patient who presented with an adenolymphoma of the parotid,
      and developed a severe nephrotic syndrome due to membranous nephropathy 6 months
      after the parotid swelling. The nephrotic syndrome resolved following
      parotidectomy and a short course of immunosuppression with prednisolone and
      cyclophosphamide. The possible pathophysiologic mechanisms are discussed.

PMID- 8856274
TI  - Case of a parathyroidectomized patient observed longitudinally by
      ultrasonography. Relationship between the growth rates and 1,25-dihydroxyvitamin
      D3 receptor contents in the parathyroid glands.
AB  - Parathyroid glands enlarge gradually with the progression of secondary
      hyperparathyroidism. The significance of down-regulation of the 1,25
      dihydroxyvitamin D receptor (VDR) in parathyroid glands has been emphasized. Here
      we report a case in whom the relationship between the growth rates of the
      parathyroid glands and their VDR content was examined. A 36-year-old man, who had
      been hemodialyzed for 8.8 years because of chronic renal failure due to chronic
      glomerulonephritis, developed severe secondary hyperparathyroidism. The first
      ultrasonographic examination of the parathyroid glands, performed 10 months
      before parathyroidectomy, revealed that the sizes of the right upper (RU) and
      left upper (LU) glands were 10 x 8 x 5 and 14 x 10 x 9 mm3, respectively,
      although the right lower (RL) and left lower (LL) glands were not detected. The
      second ultrasonographic examination performed 5 days before PTX revealed that the
      RU gland had enlarged up to 24 x 12 x 10 mm3, while the LU gland remained
      unchanged at 16 x 9 x 8 mm3. At this time, the sizes of the RL and LL glands were
      determined only in the longitudinal section to be 10 x 5 and 4 x 3 mm2,
      respectively. In the excised specimens, the sizes and weights of the RU and RL
      glands were 25 x 10 x 9 mm3 and 1,950 mg and 17 x 10 x 8 mm3 and 1,160 mg,
      respectively, while those of the LU and LL glands were 16 x 10 x 7 mm3 and 850 mg
      and 9 x 8 x 7 mm3 and 350 mg, respectively. Histopathologic study demonstrated
      that the RU and RL glands exhibited nodular hyperplasia, while the LU and LL
      glands exhibited diffuse hyperplasia. Using a ligand binding assay, the VDR
      content of the rapidly growing RU and RL glands were significantly reduced to
      32.6 +/- 9.6 and 32.7 +/- 5.2 fmol/mg protein, respectively, as compared to that
      of the LU gland with no significant proliferating activity (111.8 +/- 0.8 fmol/mg
      protein). It is of great interest that the smallest LL gland, which showed some
      proliferating potential in spite of a histologic pattern of diffuse hyperplasia,
      has a VDR content of 41.0 +/- 2.6 fmol/mg protein. In summary, it was implied
      from this case that the VDR content in the parathyroid gland might reduce as the
      growth rate of the parathyroid gland increases and, furthermore, that the VDR
      content seems to depend to some degree on the histopathologic pattern rather than
      on gland weight.

PMID- 8856275
TI  - Antineutrophil cytoplasmic antibodies (ANCA)-associated crescentic
      glomerulonephritis and propylthiouracil therapy.
AB  - Cutaneous vasculitis is an uncommon complication of propylthiouracil therapy.
      Although its pathogenesis remains to be established, detection of antineutrophil
      cytoplasmic antibodies (ANCA) in association with this type of vasculitis has
      recently been described. We report here 2 patients who developed ANCA-associated
      crescentic glomerulonephritis without evidence of cutaneous vasculitis during
      propylthiouracil treatment of hyperthyroidism. Improvement of the renal function
      and the disappearance of ANCA were correlately found after discontinuation of
      propylthiouracil and by corticosteroid therapy in both patients.

PMID- 8856276
TI  - Significance of lymphocyte fatty acid changes in chronic renal failure.
AB  - In the present study we describe fatty acid fluctuations in peripheral blood
      lymphocytes of patients with chronic renal failure who were undergoing
      maintenance hemodialysis. The decreased concentrations of linoleic acid and
      arachidonic acid and the increase in stearic acid are discussed in relation to
      the lymphocyte immune response and lymphocyte membrane enzymic systems in the
      disease.

PMID- 8856277
TI  - 1,5-anhydroglucitol as a marker for the differential diagnosis of acute and
      chronic renal failure.
AB  - Serum creatinine and 1,5-anhydroglucitol (1,5-AG) were measured in 21 non
      dialysis acute renal failure (ARF) and 32 chronic renal failure (CRF) patients.
      Fasting blood glucose was under 100 mg/dl and no patient had a history of
      diabetes mellitus. Serum 1,5-AG decreased with increase in serum creatinine in
      CRF, but not in ARF patients. A significant negative correlation was found
      between serum 1,5-AG and creatinine in CRF patients (r = -0.592, p < 0.001).
      Serum 1,5-AG in patients with serum creatinine of 4 mg/dl or more was less than
      the lowest limit of the normal range in 14 of 15 CRF patients, but only 2 of 12
      ARF patients. In these 27 patients, serum 1,5-AG was significantly higher in ARF
      than CRF (19.0 +/- 5.9 vs. 7.2 +/- 4.1 micrograms/ml, p < 0.01). From these
      results, it would follow that serum 1,5-AG should serve effectively as a marker
      for the differential diagnosis of nondiabetic ARF and CRF.

PMID- 8856278
TI  - Malignant tumors in hemodialysis patients.
AB  - We reviewed the incidence of malignant tumors among 923 patients with chronic
      renal failure, treated with hemodialysis (HD) in seven dialysis centers in Serbia
      between January 1983 and July 1993. Neoplasms were diagnosed in 45 cases (4.9%).
      The mean age of the cancer patients was 58.7 years. Eighteen cases (40.0%) were
      diagnosed in the first year after starting HD treatment and 21 (46.7%) cases were
      detected less than 5 years after induction of HD treatment. Most of the cancer
      patients (60.0%), especially the patients with Balkan endemic nephropathy
      (31.1%), developed cancer of the urinary tract. We concluded that HD patients
      have a several times greater risk of developing malignant tumors than the general
      population.

PMID- 8856279
TI  - Cholesterol and triglyceride content in lipoprotein fractions of rats treated
      with bovine serum albumin.

PMID- 8856280
TI  - Leukocyte flow properties, polymorphonuclear membrane fluidity and cytosolic Ca2+
      content in chronic renal failure.

PMID- 8856281
TI  - Treatment of severe leukopenia with RHG-CSF in systemic lupus erythematosus
      treated with cyclophosphamide.

PMID- 8856282
TI  - Membranoproliferative glomerulonephritis associated with insulin-dependent
      diabetes mellitus. A case report.

PMID- 8856283
TI  - Serum lipoprotein (a) levels in renal transplantation: role of renal function.

PMID- 8856284
TI  - Intravenous immunoglobulins modify the response to erythropoietin in a CAPD
      patient.

PMID- 8856285
TI  - Teicoplanin-induced thrombocytopenia.

PMID- 8856286
TI  - Clinical evaluation of bone metabolism after renal transplantation to support the
      theory to perform 1,25(OH)2D3 pulse therapy before transplantation.

PMID- 8856287
TI  - Interaction between azithromycin and cyclosporin?

PMID- 8856288
TI  - Acute interstitial nephritis due to cefotaxime.

PMID- 8856289
TI  - High risk of retinal damage by desferrioxamine in dialysis patients.

PMID- 8856290
TI  - Persistent renal failure in acute myelomonocytic leukemia. Possible role of
      massive leukemic infiltration in the renal interstitium.

PMID- 8856291
TI  - Primary biliary cirrhosis complicated with Sjogren syndrome and multiple myeloma.
      A case report.

PMID- 8856292
TI  - Acute renal failure associated with mannitol infusion and reversal with
      ultrafiltration and hemodialysis.

PMID- 8856293
TI  - Blood hepatocyte growth factor levels in chronic renal failure patients.

PMID- 8856294
TI  - Severe rhabdomyolysis induced by a retard formulation of bezafibrate in a CAPD
      patient.

PMID- 8856295
TI  - Death from suicide and discontinuation of renal replacement therapy: 23-years'
      clinical experience.

PMID- 8856296
TI  - Effects of the intravenous magnesium administration on aldosterone and atrial
      natriuretic factor plasma concentrations.

PMID- 8856297
TI  - Influence of bioethics in investigation and treatment in oncology.

PMID- 8856298
TI  - Two synchronous primary tumors of the ovary and kidney: a case report.
AB  - Multiple malignancies in the same patient account for 1.84% to 3.9% of all
      cancers. However, multiple synchronous primary tumors in the same patient are
      extremely rare. Most synchronous double primary cancers are seen in both the
      genitourinary and gastrointestinal tracts. Synchronous double primary tumors
      involving kidney and ovary have been reported once in the Japanese literature;
      however, there are no reported cases in the English literature. This 66-year-old
      woman underwent radical nephrectomy for her renal cancer and optimal tumor
      reductive surgery for her ovarian cancer. She was started on carboplatin and
      cyclophosphamide therapy for her residual ovarian cancer. On follow-up after 8
      months, the patient is alive and well with no evidence of disease. In this report
      we present the first case in the English language literature of synchronous
      primary cancers in the right ovary and right kidney.

PMID- 8856299
TI  - Hyperestrogenemia and presence of estrogen receptors associated with an
      epithelial ovarian tumor of low malignant potential.
AB  - An 80-year-old woman presented with breast congestion, tenderness and pain.
      Mammography was normal. Circulating estradiol was markedly elevated, while LH and
      FSH were low. Pelvic examination and imaging revealed an ovarian mass which was
      extirpated during total abdominal hysterectomy and bilateral salpingo
      oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of
      low malignant potential, stage 1. The tumor was positively stained for estrogen
      receptors. Estradiol levels returned to normal post-operatively, with a
      corresponding adjustment of LH/FSH. Possible autocrine steroid production is
      discussed.

PMID- 8856300
TI  - Prolonged stabilization of progressive platinum-refractory ovarian cancer with
      paclitaxel: brief report.
AB  - Platinum-based chemotherapy is the standard treatment for ovarian cancer, with
      response rates of 70-80% and pathologic complete remissions of 20-25%. Salvage
      therapy with paclitaxel has an established role in patients with platinum
      refractory ovarian cancer. In non-randomized trials, high doses have tended to be
      more effective. In this report, we describe two patients with platinum-refractory
      ovarian cancer who received paclitaxel and had long-term stabilization of their
      disease. One patient received 250 mg/m2 paclitaxel for 38 cycles; the other 135
      mg/m2 for 30 cycles. Both patients received granulocyte colony-stimulating factor
      (G-CSF) support to prevent severe granulocytopenia; neither experienced
      cumulative hematopoietic nor neurologic toxicity. Their quality of life was good
      throughout the treatment.

PMID- 8856301
TI  - Prognostic significance of epidermal growth factor receptor (EGFR) and c-erbB-2
      protein overexpression in adenocarcinoma of the uterine cervix.
AB  - The authors studied the prognostic value of EGFR and c-erbB-2 overexpression in
      adenocarcinoma of the uterine cervix. The aim of this research was to find a new
      pathway to prognosis for more adequate therapy.

PMID- 8856303
TI  - Hysteroscopy in gestational trophoblastic diseases.
AB  - Hysteroscopic evaluations were performed in eight women with gestational
      trophoblastic diseases. Seven of the eight patients had abnormal hysteroscopic
      findings and biopsies were obtained from the endometrium and adjacent myometrium.
      Five patients had histopathological proof of tumour. This preliminary report
      shows the feasibility of the method. The potential risks involved are discussed.
      A correct histopathological diagnosis in patients evaluated for gestational
      trophoblastic diseases may be useful in order to tailor the treatment.

PMID- 8856302
TI  - Unusual presentation of a metastatic choriocarcinoma following a full term
      pregnancy: a case report.
AB  - Choriocarcinoma most commonly follows a molar pregnancy, but it may develop after
      any gestational event. If choriocarcinoma follows a term pregnancy, it is
      associated with an unfavorable outcome and a 60% survival rate. A 33 year female
      who had delivered a normal girl 4 months before, presented with a nodule on the
      scalp behind the right ear. The pathologic diagnosis was compatible with
      metastatic choriocarcinoma. This tumor did not respond to chemotherapy, and she
      died a year later of multiple liver and pulmonary metastases. The development of
      a choriocarcinoma following a full term pregnancy is associated with a poor
      prognosis. We suggest that patients who do not achieve a clinical or serological
      remission after EMA-CO treatment be considered for high dose chemotherapy such as
      transplant.

PMID- 8856304
TI  - Comparison of surgical and postoperative complications of vaginal hysterectomy
      and Manchester procedure.
AB  - OBJECTIVE: The Manchester procedure (MP) was compared to vaginal hysterectomy
      (VH). Surgical and postoperative complications were evaluated. MATERIAL AND
      METHODS: A retrospective review of women undergoing VH and MP for uterine
      prolapse was performed. All the operations were performed between 1974-1994. MP
      was performed in 190 patients and VH (Heaney technique) in 231 women. RESULTS: MP
      patients, when compared to VH patients, were more likely to be older and
      postmenopausal at the time of surgery. Statistically significant differences were
      found for operative time and blood loss. This difference was not dependent on the
      performance of anterior or posterior repair. CONCLUSIONS: We suggest the use of
      MP as an alternative to VH in the absence of uterine pathology in appropriate
      candidates with uterine prolapse.

PMID- 8856305
TI  - Symptomatic hypocalcemia and hypomagnesiemia in cisplatinum-based chemotherapy
      treated patients: case report.

PMID- 8856306
TI  - Relation between infection with human papilloma viruses and expression of p21 and
      p53 oncoproteins in patients with cancer of the uterine cervix.
AB  - Infection with HPV type 16 was demonstrated in 54% of the cases and infection
      with HPV type 18 in 36.5% of the cases of uterine cervix carcinoma. Both types of
      viruses were present in 24.3% of the patients. P53 protein accumulation in cell
      nuclei was observed in 12.2% of the cases of uterine cervix carcinomas and the
      cases were mostly HPV negative while the cytoplasmic expression of p53 protein
      was present in 39% of the cases and was frequently accompanied by HPV infection.
      Presence of p21 protein was detected in 85.3% of the cases, independently of HPV
      infection or expression of p53 protein.

PMID- 8856307
TI  - Leuprolide acetate as a salvage-therapy in relapsed epithelial ovarian cancer.
AB  - A large number of studies have been conducted in patients affected by epithelial
      ovarian cancer to assess the potential utility of a variety of different regimens
      in patients who have relapsed after primary surgery and adjuvant chemotherapy. In
      this open prospective study, 32 patients with ovarian cancer of epithelial
      histology who had relapsed after platinum-based line chemotherapy and had
      exhausted all standard treatments, received Leuprolide acetate depot 3.75 mg,
      intramuscularly once a month until tumor progression. Four patients (12.5%) had
      clinical and/or radiological partial response; remission was then maintained for
      a mean duration of 8.7 months (range 6-11 months) before new progression
      occurred. Five patients (15.6%) remained stable for a mean time of 5.2 months
      (range 4-6 months) and 23 patients (71.9%) continued to progress following
      therapy and have since died by tumor with a median survival of 3.6 months after
      initiation of the protocol. Treatment is well-tolerated and no toxicity has been
      noted. These data stress the significant activity of Leuprolide acetate as a
      salvage therapy in patients with relapsed advanced epithelial ovarian cancer
      after previous platinum-based chemotherapies.

PMID- 8856308
TI  - The use of combined chemotherapy for the treatment of advanced sarcoma of the
      uterus.

PMID- 8856309
TI  - Epidemiology and clinical management of endometrial carcinoma in the Republic of
      Georgia in the last 30 years.
AB  - Endometrial carcinoma incidence in Georgia from 1965 to 1992 was 5.3 women per
      100,000 and in the structure of gynecological malignant tumors this pathology
      occupied third place (19.1%). Morbidity incidence varied from 2 to 8 depending on
      ethnic regions overall a 2.5 times rise in morbidity was observed. Within the
      period of 1968-1994 1731 patients with uterine carcinoma were subjected to
      surgical intervention (stage I-81.2%; stage II-9.4%; stage III-9.0%; stage IV
      0.3%). Surgical intervention is the optimal method to determine the stage of the
      disease and planning of adjuvant treatment. Metastases in regional lymph nodes
      were found in 13.0% (T1-7.7%; T2-20.07%; T3-35.3%). Adenocarcinoma was
      histologically confirmed in 97.4% (G1-21.3%; G2-57.8%; G3-18.8%). Management of
      the disease was predominantly started with surgical intervention. In pathogenetic
      version I (71.4%) total extirpation of the uterine was carried out, while in
      cases of the pathogenetic version II (28.6%) patients were subjected to the
      modified extended extirpation. Postoperative management was prescribed based on
      the peculiarities of the organism and tumor. Highly sensitive classification of
      endometrial carcinoma of stage I (including 5 subgroups) as well as a synoptic
      table of optimal management were worked out. As a result, 5 year survival
      increased by 15%, and 29% of the women operated were spared from additional
      treatment. On the whole, five-year-survival was observed in 71.0% of women (stage
      I-77.7%; Early Form-95.5%; stage II-51.5%; stage III-34.2%).

PMID- 8856310
TI  - Detection of HPV 16 and HPV 18 infection in patients with cervical neoplasia.
AB  - Definite types of human papillomaviruses (HPV) are considered an etiological
      factor in the occurrence of cervical carcinoma. Determining the persistence of
      some HPV types associated with cervical carcinoma is important in defining and
      following precancerous lesions. The most sensitive method in the determination of
      these viruses is polymerase chain reaction (PCR). Because of the convenience and
      the fastness it provides, cytological cervical material is preferred for the
      analysis. In our study infection with HPV 16 and HPV 18 was investigated in the
      cervical scrapes of 33 subjects with cervical carcinoma. The DNAs isolated from
      the samples were amplified by PCR. HPV 16 and HPV 18 types were identified by
      Southern Blot hybridization. The positivity rates for HPV 16 and HPV 18 in 33
      subjects with cervical carcinoma were 54.5% and 45.4%, respectively. The
      corresponding value in the control group was only 5.5%. PCR combined with
      Southern Blot is the most sensitive method for scanning programmes and in
      defining and monitoring the risk groups for developing cervical neoplasia.

PMID- 8856312
TI  - Relapse of acute lymphoblastic leukemia during pregnancy.
AB  - A young woman had a late relapse from acute lymphoblastic leukemia during her
      first pregnancy at the 17th week of gestation and decided not to interrupt the
      pregnancy. A partial remission was obtained with mild chemotherapy (vincristine
      and prednisone) in a month, then the treatment was intensified, but only partial
      remission was achieved. A cesarean section was performed at the end of the 7th
      month, with the delivery of a normal male infant. The patient died of refractory
      leukemia 9 months later. The baby is now 3 years old with no medical problems.
      This case suggests that: a) pregnancy might be associated with an increased risk
      of relapse in women in continuous complete remission from leukemia; b)
      chemotherapy, even intensive, can be safely administered to pregnant women
      without damaging the fetus, after the first trimester.

PMID- 8856311
TI  - Recurrent mucinous adenocarcinoma of the ovary presenting as an inguino-labial
      hernia.
AB  - We report a case of a 65-year-old woman who nine years previously had undergone
      total abdominal hysterectomy and bilateral salpingoophorectomy for a large
      ovarian cyst. During surgery the cyst had ruptured and some mucinous material had
      been spilled intraabdominally. Histopathological studies demonstrated the cyst to
      be a mucinous adenocarcinoma of low malignant potential. Appendectomy had also
      been performed due to an enlarged appendix, which proved to be a mucocoele. The
      patient had been lost to subsequent follow-up. Her current presenting symptom was
      a giant inguino-labial hernia of 25 cm diameter with two small skin perforations
      leaking a gelatinous discharge. Subsequent laparotomy and inguinal exploration
      have disclosed herniated small intestine with an attached metastatic multicystic
      mucinous adenocarcinoma. This case represents a case of borderline mucinous adeno
      carcinoma-pseudomyxoma peritonei recurring in a unique pattern as a huge inguino
      labial hernia, and serves to emphasize the possible consequences of spillage of
      ovarian cyst contents during surgery.

PMID- 8856313
TI  - Rapidly progressive squamous cell carcinoma of the cervix in a patient with
      acquired immunodeficiency syndrome: case report.
AB  - Recent evidence suggests an association between cervical condyloma, dysplasia and
      HIV infection. However, the course of cervical cancer in immunodeficient patients
      has not yet been thoroughly researched. Cervical cancer presently amounts to 1%
      of the causes of death in AIDS patients. This percentage is bound to increase not
      only because an improved life expectancy has been obtained, but mainly because
      the virus is widely spreading among the female population. A 28 year-old AIDS
      patient, parity 1/0/1/1, underwent gynecological examination and colposcopy
      following an episode of vaginal bleeding. Biopsy revealed an invasive cervical
      carcinoma. The last gynecologic investigation, which included a Pap smear and
      colposcopy, was performed 14 months earlier and resulted negative. Cytologic
      reexamination of the specimen confirmed the previous Pap smear result.
      Proctoscopy and cystoscopy showed no mucose involvement. Urography was negative.
      The cat scan indicated minor spleen and liver enlargement but no signs of
      malignant abdominal spread were found. The neoplasia was classified as a stage
      IIB cervical carcinoma (according to the FIGO classification) due to the spread
      to the left cardinal ligament. In spite of radiation therapy, the disease rapidly
      progressed leading to a monolateral ureteral involvement which created a
      juxtavescical stenosis. The patient died three months later. Necroscopic
      examination revealed lung metastasis. Such a rapidly progressive form of cervical
      cancer could be related to the acquired immunodeficiency condition. Recurrent
      cytological and colposcopic examinations are to be considered mandatory in HIV
      patients.

PMID- 8856314
TI  - Enteric type villoglandular papillary adenocarcinoma of the uterine cervix
      associated with in situ squamous cell carcinoma. Case report and review of the
      literature.
AB  - A very rare case of enteric-type villoglandular papillary adenocarcinoma of the
      uterine cervix associated with in situ squamous cell carcinoma in a 21-year-old
      nulliparous caucasian woman is reported. Adjacent to the infiltrative component
      of an enteric-type lesion, cervical intraepithelial glandular neoplasia (CIGN)
      was also noticed. Histochemical detection of acetylated sialomucins demonstrates
      the enteric-type nature of this neoplastic (via metaplasia) process. The patient
      was treated by conization. Follow-up was uneventful one year after diagnosis.

PMID- 8856315
TI  - Tumor-associated urokinase-type plasminogen activator: significance in breast
      cancer.
AB  - Urokinase-type plasminogen activator (u-PA), a proteolitic enzyme, capable of
      degrading type 4 collagen, is supposed to be involved in degradation of
      extracellular matrix during cancer invasion. Evidence has been presented that
      primary breast cancer patients with tumors containing high levels of u-PA
      experience a worse prognosis. u-PA and its inhibitor, type 1 plasminogen
      activator inhibitor (PAI-1), are potentially important prognostic factors in
      breast cancer to identify patients at high risk for recurrence and also in the
      classification of clinically important subgroups.

PMID- 8856316
TI  - Metastatic breast carcinoma manifesting as postmenopausal uterine bleeding in a
      patient on tamoxifen therapy.
AB  - A rare case of breast carcinoma metastasizing to the endometrial and endocervical
      mucosa during tamoxifen treatment is presented. Routine histologic evaluation has
      been supplemented by immunohistochemical staining for intermediate filaments.
      Although the association of tamoxifen therapy for breast carcinoma with the
      development of endometrial carcinoma is well known, this is, to the best of our
      knowledge, the first report of metastatic breast carcinoma to the uterus of a
      patient on tamoxifen therapy.

PMID- 8856317
TI  - Enzyme electrophoresis combined with serogrouping for improved differentiation of
      Clostridium difficile strains.
AB  - We used enzyme electrophoresis to study a set of epidemiologically related and
      unrelated isolates of Clostridium difficile. The 53 strains belonged to the most
      frequent serogroups (A1, C, G, H and K). Nine electrophoretic profiles were
      defined on the basis of five enzymes, and two were characteristic of a single
      strain. Each serogroup was resolved into two or three different enzyme patterns.
      By combining the two methods we were able to resolve the strains into 12 types.
      There was an excellent correlation between enzyme electrophoresis and
      serogrouping data. This method may be of use in investigating nosocomial
      transmission.

PMID- 8856318
TI  - Role of capsular sialic acid in virulence and resistance to phagocytosis of
      Streptococcus suis capsular type 2.
AB  - Streptococcus suis capsular type 2 has a capsule rich in sialic acid (NANA).
      Sialic acid, known to be an antiphagocytic factor for many bacterial species,
      inhibits the activation of the alternative complement pathway. The role of
      capsular NANA in virulence, resistance to phagocytosis and intracellular survival
      of S. suis capsular type 2 was evaluated. In general, a low concentration of NANA
      was observed for all the S. suis strains tested. In addition, no difference could
      be found in NANA concentrations between strains of different virulence degrees.
      Sialic acid concentration increased in the virulent strain 89-1591 and the
      avirulent strain 90-1330 after in vivo growth with an increased capsular material
      thickness compared to growth in vitro. No significant difference could be found
      in the phagocytosis rate by porcine blood monocytes of either strain and strain
      89-1591 treated with sialidase or the sialic acid-binding lectin from Sambucus
      nigra (SNA I). Intracellular survival of strain 89-1591 decreased after
      treatments with sialidase or lectin, becoming comparable to that of strain 90
      1330. Finally, no difference could be seen in virulence using a murine model,
      even if strain 89-1591 was treated with the enzyme or the lectin. Thus, NANA does
      not seem to be a critical virulence factor for S. suis capsular type 2.

PMID- 8856319
TI  - Inhibition of adhesion of Clostridium difficile to Caco-2 cells.
AB  - For many microorganisms, including Clostridium difficile, mucosal association is
      an important factor influencing intestinal colonisation and subsequent infection.
      Inhibition of adhesion of C. difficile to intestinal mucosa could be a new
      promising strategy for prevention and treatment of antibiotic-associated
      diarrhoea. We investigated the possibilities of influencing the adhesion of C.
      difficile by xylitol and bovine colostrum whey. Caco-2 cells and C. difficile
      cells were incubated with 1%, 5% and 10% solutions of xylitol and colostrum. Our
      study revealed that both xylitol and colostrum inhibited the adhesion of C.
      difficile to Caco-2 cells. Inhibition by xylitol was dose-dependent. When
      compared to the control, the count of adherent C. difficile decreased 3.4 times
      when treated with 1% xylitol, 12 times when 5% xylitol was applied, and 18.7
      times when treated with 10% xylitol. The inhibition of adherence by colostrum was
      partially dose-dependent: 3.1 times in the case of 1%, and 5.5 times in the cases
      of 5% and 10% colostrum. Further experimental and clinical studies are needed for
      the application of xylitol and colostrum in the treatment and prophylaxis of
      pseudomembraneous colitis.

PMID- 8856320
TI  - Binding diversity of monoclonal antibodies to alpha(2-->8) polysialic acid
      conjugated to outer membrane vesicle via adipic acid dihydrazide.
AB  - Murine monoclonal antibodies (mAbs) were generated using group B Neisseria
      meningitidis and Escherichia coli K1 polysaccharides (PSs) conjugated to outer
      membrane vesicle (OMV) via adipic acid dihydrazide, and were used to identify the
      immunodeterminants expressed on these capsular PSs. Ten mAbs representative of
      IgM and all subclasses of IgG were obtained which recognized diverse
      immunodeterminants on alpha(2-->8) polysialic acid (PSA). The specificity of mAbs
      to different antigenic determinants was assessed by their differential binding to
      PSA attached to a solid phase by different methods and confirmed by absorption
      studies. Two mAbs from the E. coli K1 fusion were directed to the O-acetyl
      epitope and the rest reacted with both the PSs only when attached to a solid
      phase by certain means. The methods by which PSA was coated on the solid phase
      had an impact on the epitope expression and binding pattern. At the
      concentrations used, the O-acetyl-specific mAbs, IgG1 and IgG3 mAbs were not
      bactericidal against group B N. meningitidis, whereas other mAbs were. The
      conjugates B and K1 PSs present to the murine immune system different antigenic
      determinants, some of which elicit bactericidal antibodies.

PMID- 8856321
TI  - DNA immunization: effects of vehicle and route of administration on the induction
      of protective antiviral immunity.
AB  - The effectiveness of DNA immunization has been demonstrated in several model
      systems, usually following intramuscular injection of DNA in saline, or topical
      administration to the skin. In this study we have compared DNA delivered by three
      routes (intramuscular, intravenous, and intraperitoneal) and, for each route, in
      two vehicles (cationic liposome complex and pH sensitive liposome). These two
      lipid vehicles were evaluated because they are frequently used in gene therapy
      studies, but their immunogenicity has not been extensively studied. Each of these
      six combinations has been evaluated not only by assay of marker gene expression
      in a variety of tissues, but also by measurement of biologically-relevant
      parameters of immunity induction of antibodies, cytotoxic T lymphocytes, and
      protection against viral challenge. By both criteria (marker gene expression and
      induced immunity), the outcomes vary markedly among the six combinations. The
      combination leading to maximal marker gene expression (DNA with cationic lipid,
      administered i.v.) also induces detectable antibodies and CTL, and is the only
      one of the six combinations to induce immune responses comparable to those seen
      following i.m. injection of DNA in saline. However, marker gene expression can be
      detected in other combinations in the absence of induced immunity thus the value
      of marker gene expression in predicting the protection induced by a microbial
      antigen is questionable suggesting that, when evaluating various promoter
      constructs, marker gene expression may not adequately replace the direct
      measurement of biological outcomes.

PMID- 8856322
TI  - Molecular evidence supporting the existence of two major groups in uropathogenic
      Escherichia coli.
AB  - Molecular methods allow an extremely fine strain typing that can be used to
      establish the population structure of bacterial species. This methodology has
      been used to characterize a collection of 74 uropathogenic Escherichia coli
      obtained from three hospitals located in geographically distant towns in Spain,
      some representatives of the ECOR collection and other reference strains. Genomic
      DNA was analyzed by RAPD (Random Amplified Polymorphic DNA) that can characterize
      a bacterial strain to the level of defining individual clones. The 16S rDNA-23S
      rDNA spacers were amplified by PCR and submitted to restriction analysis.
      Finally, the presence or absence of G adhesins in Escherichia coli as well as the
      type of adhesin (three types are known) have been shown by PCR amplification
      followed by digestion with restriction enzymes. As expected a wide diversity was
      shown by RAPD and identical patterns were only found in the case of strains
      isolated from the same individual, an obvious case of relapse. Analysis of the
      spacers' restriction patterns showed the presence of two markedly differentiated
      clusters that we have named alpha and beta. Both RAPD and spacer restriction
      patterns originated similar clusters of strains showing a consistency in the
      evolution of the global genome with the sequence variation of the ribosomal
      spacers. Furthermore, most of the strains having G-adhesin, with only a few
      exceptions, corresponded to the alpha rRNA spacer group. The two spacer types
      detected were also consistent with some phenotypic markers such as sucrose and
      raffinose utilization. The alpha and beta clusters could be intraspecific groups
      produced by partial sexual isolation or other barriers that are originating a
      divergent evolution.

PMID- 8856323
TI  - Ultrastructural localization of glycogen phosphorylase predominantly in
      astrocytes of the gerbil brain.
AB  - The localization of glycogen phosphorylase in gerbil brain was determined by
      immunoelectron microscopy using the pre-embedding peroxidase technique. Electron
      dense granular reaction product of peroxidase activity was observed in astrocytes
      of all brain regions examined (cerebral cortex, striatum, cerebellar cortex,
      hippocampal formation, corpus callosum, mesencephalic trigeminal nucleus). The
      reaction product was distributed in a diffuse pattern throughout the cytoplasmic
      matrix of perikarya and processes; sometimes the nucleus of labeled astrocytes
      also contains immunopositive material. The light microscopically visible glycogen
      phosphorylase immunoreactivity associated with capillaries could be characterized
      as a staining of astrocytic endfeet ensheathing capillaries. Endothelial cells
      and pericytes were never labeled. In addition to astrocytes, ependymal cells also
      presented immunopositive material in their cytoplasm. On the other hand, no
      reaction product was observed in cells identified as oligodendroglia or
      microglia. Neurons (with the exception of neurons of the mesencephalic trigeminal
      nucleus), their processes, and their synaptic endings were free of reaction
      product. In the neuropil we frequently observed immunopositive glial processes
      adjacent to synaptic structures. This intimate spatial relationship may be
      interpreted as a morphological sign of a metabolic interaction. The data support
      the hypothesis that astroglia play a key role in glycogen metabolism and
      energization of the brain.

PMID- 8856324
TI  - Electrical coupling among Bergmann glial cells and its modulation by glutamate
      receptor activation.
AB  - We studied the characteristics of electrical coupling between Bergmann glial
      cells in mouse cerebellar slices using Lucifer Yellow injection, patch-clamping
      cell pairs, and ultrastructural inspection. While early postnatal cells (days 5
      7) were not coupled, coupling was abundant at postnatal days 20-24. Coupled cells
      were arranged perpendicular to the parallel fibers in a parasagittal section,
      forming a string, rather than a cluster of cells. Electron microscopy revealed
      that gap junctions were abundant in the distal parts of the processes. Gap
      junctions between cell bodies and processes were very rare, and no gap junctions
      were found between cell bodies of adjacent Bergmann glial cells. The junctional
      conductance was voltage and time independent and could be markedly reduced by
      halothane. Alkalization of cells (by applying NH4+) increased the junctional
      conductance to 150%, while acidification of the cell interior (by removing NH4+)
      led to a decrease to 70%. Activation of AMPA receptors induced a blockade of the
      junctional conductance to 30% of the control. This link is most likely mediated
      by the influx of Ca2+ via the receptor since this effect was not observed in
      Ca(2+)-free medium, suggesting that Ca2+ entry via the kainate receptor pore led
      to the closure of gap junctions. These studies indicate that electrical coupling
      between Bergmann glial cells is not only developmentally regulated but also
      controlled by physiological stimuli.

PMID- 8856325
TI  - Swelling of Muller cells induced by AP3 and glutamate transport substrates in rat
      retina.
AB  - Previous studies have shown that a single systemic injection of 2-amino-3
      phosphonopropionate (AP3), an agonist/antagonist at metabotropic glutamate
      receptors, produces marked swelling of rodent Muller cells. To investigate the
      effects of AP3 on Muller cells, we used in vitro retinal segments prepared from
      30 day old rats. Incubation with AP3 for 1 h or more caused severe swelling of
      Muller cells with the appearance of mitotic cellular profiles in the outer
      nuclear layer. The Muller cell swelling was mimicked by substrates for glutamate
      transporters, suggesting that AP3 may produce its effects via transport into
      glial cells. To determine whether AP3 is a substrate for glutamate transporters,
      we studied cultured rat hippocampal astrocytes using whole-cell patch clamp
      recordings. In hippocampal astrocytes, AP3 activated currents via an Na(+)
      dependent glutamate transporter. Consistent with this, substitution of
      extracellular sodium with choline blocked Muller cell swelling in the rat retina.
      These results indicate that the acute glial swelling produced by AP3 results
      primarily from a fluid shift that accompanies the transport of AP3 and sodium
      into Muller cells.

PMID- 8856326
TI  - Beta 4 integrin and other Schwann cell markers in axonal neuropathy.
AB  - Schwann cell gene expression is dynamically regulated after peripheral nerve
      injury and during regeneration. We hypothesized that the changes in protein
      expression described after rat peripheral nerve injury could be used to identify
      single Schwann cell-axon units in human axonal neuropathy. Therefore, we
      performed immuno-fluorescence staining on sections of injured rat sciatic nerves
      compared with sections of neuropathic human sural nerves. We chose the markers
      beta 4 integrin, P0 glycoprotein, and glial fibrillary acidic protein (GFAP) to
      characterize Schwann cells, and neurofilament-heavy (NF-H) to recognize axons.
      Normal rat or human myelin-forming units demonstrated a sharp ring of beta 4
      staining at their outer surface, P0 staining in the myelin sheath, and NF-H
      staining in the axon. Acutely denervated rat units transited from broken rings of
      beta 4 and P0 staining, to diffuse beta 4 and absent P0 and NF-H staining.
      Chronically denervated rat Schwann cells re-expressed beta 4 more highly, but in
      a diffuse, non-polarized pattern. In contrast, regenerating units re-expressed
      beta 4, P0, and NF-H; beta 4 staining was polarized to the outer surface of
      Schwann cells. Finally, GFAP staining increased progressively after injury and
      decreased during regeneration in the distal nerve stump. In neuropathic human
      sural nerves, we identified units exhibiting each of these beta 4, P0, and NF-H
      staining patterns; the proportion of each pattern correlated best with the extent
      and chronicity of axonal injury. Thus, synchronous injury of rat sciatic nerve
      predicts patterns of Schwann cell marker expression in human axonal neuropathy.
      In addition, the unique changes in the polarity of beta 4 integrin expression, in
      combination with changes in P0 and NF-H expression, may distinguish normal from
      denervated or reinnervated myelin-forming Schwann cells in human sural nerve
      biopsies.

PMID- 8856327
TI  - The ordered array of perivascular macrophages is disrupted by IL-1-induced
      inflammation in the rabbit retina.
AB  - In this study we have shown that an antibody to CD18 identified a population of
      cells in the rabbit retina that resembled the perivascular macrophage found in
      other regions of the central nervous system. In the normal retina these cells
      possessed a ramified morphology and presented in an ordered array on the vitreal
      surface in association with the epiretinal vessels. Approximately 50% of the
      perivascular macrophages constitutively expressed MHC class II. In response to
      interleukin-1 beta (IL-1 beta)-induced inflammation, these cells became
      activated, as evidenced by a change from a ramified to an ameboid morphology and
      increased expression of MHC class II, and migrated away from the vessels. These
      changes were first detected around 3 h post-intraocular challenge coincident with
      the onset of inflammation. At the peak of the inflammatory response
      (approximately 24 h post-challenge), many activated perivascular macrophages were
      no longer associated with the vessels and formed long "cord" of MHC class II+
      cells associated with underlying deposits of fibrin. In eyes challenged with heat
      inactivated IL-1, no change in the morphology or distribution of the perivascular
      macrophage was noted. At 3 weeks post-challenge with IL-1, the number and
      distribution of the perivascular macrophages were restored to baseline values,
      although with a reduced cell size. Since these changes closely resemble those
      that occur in non-lymphoid dendritic cells in the skin, heart, and/or kidney
      following activation with cytokines or bacterial products, the results suggest
      that the perivascular macrophage represents the dendritic cell of the retina and
      may thus play an important role in immune surveillance in the eye and maintenance
      of the blood-retina barrier.

PMID- 8856328
TI  - The 5HT5A serotonin receptor is expressed predominantly by astrocytes in which it
      inhibits cAMP accumulation: a mechanism for neuronal suppression of reactive
      astrocytes.
AB  - The mRNA for the 5-hydroxytryptamine receptor 5-HT5A was detected at embryonic
      day 18 in the rat central nervous system and peaked by postnatal day 20. At all
      time points examined, 5-HT5A immunoreactivity observed on astrocyte cell bodies
      and in the stellate processes not only colocalized with the astrocyte-specific
      marker glial fibrillary acidic protein (GFAP) but was coordinately regulated with
      GFAP, increasing during development and during gliosis. Transfection of 5-HT5A
      into glioma cells prevented the 5-HT-induced increase in cAMP observed in
      untransfected cells and decreased the relative forskolin response by
      approximately 20%, suggesting that the 5-HT5A receptor couples negatively to
      adenylyl cyclase in astrocytes. Together, these results indicate a neuron-to
      astrocyte serotonergic signaling pathway mediating cAMP concentrations, which
      could provide a neuronally driven mechanism for regulating astrocyte physiology
      with relevance to gliosis.

PMID- 8856329
TI  - Improved method for harvesting human Schwann cells from mature peripheral nerve
      and expansion in vitro.
AB  - The use of cellular prostheses containing large populations of Schwann cells (SC)
      has been proposed as a future therapeutic approach in the repair of neural
      tissue. We have sought to define an efficient protocol for the harvest and
      expansion of human SC from mature human peripheral nerve. We evaluated SC
      proliferation occurring within fresh explants and studied the relationship
      between certain parameters (cell yield, purity, and rate of SC proliferation) and
      the conditions of maintenance of nerve explants prior to dissociation. In
      addition, we studied SC proliferation after dissociation in a variety of
      conditions. We observed that SC within explants divide at a low rate during the
      first 3 weeks following explantation; this proliferation falls to near zero
      during the fourth week. The cell yield, SC purity, and proliferation rate
      following dissociation were all increased when nerve explants were exposed to
      heregulin/ forskolin for 2 weeks prior to dissociation. Electron microscopic
      analysis showed that heregulin/forskolin exerted trophic effects on SC within
      explants. Following dissociation, SC growth in heregulin/forskolin-containing
      medium was more rapid on laminin or collagen than on poly-L-lysine. These results
      provide new insights into human SC biology and suggest several procedural
      improvements for harvesting and expanding these cells. The new method we describe
      shortens our previous procedure by 4-6 weeks and provides a 30-50-fold increase
      in the number of SC obtained relative to the earlier procedure.

PMID- 8856330
TI  - Compartmental distribution of sulfated glycosaminoglycans in lateral and medial
      midbrain astroglial cultures.
AB  - Sulfated glycosaminoglycans (S-GAGs) were isolated from the pericellular (P),
      intracellular (I), and extracellular (E) compartments of astrocytes cultures from
      lateral (L) and medial (M) sectors of embryonic mouse midbrain; these sectors
      differ in their ability to support neurite growth (L, permissive, M, non
      permissive for growth) and laminin deposition patterns (L, fibrillar; M, punctate
      pattern). The total amount of S-GAGs in M cultures was twice that in L cultures
      and was particularly high in the P compartment of M glia. Both glial cultures
      showed heparan sulfate (HS) in the three cellular compartments but chondroitin
      sulfate (CS) GAGs were vestigial in I and P compartments of L glia. Our results
      suggest that M and L astrocytes are heterogeneous concerning the ability to
      synthesize GAGs and distribute them among the different cellular compartments.
      Together with other data (Garcia-Abreu et al: J Neurosci Res 40:471, 1995; Garcia
      Abreu et al: Neuroreport 6:761, 1995), the present results suggest that this
      heterogeneous features might be at least partially responsible for the
      differential effects of L and M glial cultures on the growth of midbrain neurons
      and may also be involved in complex ways in the guidance of axons at the brain
      midline.

PMID- 8856331
TI  - Ependymocytes and supra-ependymal axons in rat brain contain glutamate.
AB  - The cilated ependymocytes that line the ventricles are decorated by a network of
      serotoninergic supra-ependymal axons, which are thought to regulate their
      function. The neurones of origin contain both serotonin and phosphate-activated
      glutaminase, which raises the possibility that the supra-ependymal axons are also
      glutamatergic. Using immunocytochemistry, the present study has demonstrated the
      presence of glutamate in many supra-ependymal axons, as well as in the cilia of
      ependymocytes. We suggest that glutamate in supra-ependymal axons,
      counterbalances or opposes the action elicited by serotonin. Glutamate taken up
      by ependymocytes may supplement metabolic pathways in these cells and could be
      used to fuel the high energy demands of their cilia.

PMID- 8856332
TI  - Transfer of horseradish peroxidase from oligodendrocyte to axon in the
      myelinating neonatal rat optic nerve: artefact or transcellular exchange?
AB  - In this paper we make the surprising observation that intracellular injection of
      horseradish peroxidase (HRP) into a single myelinating oligodendrocyte also
      resulted in localised HRP labelling at the nodes of Ranvier of some axons of the
      unit. It appeared that HRP had been transferred to the nodal axoplasm from the
      paranodal loops of the HRP-filled oligodendrocyte. Three HRP-filled
      oligodendrocytes from isolated optic nerves of 14-day-old rats were analysed by
      serial section electron microscopy, and HRP was observed in the axonal cytoplasm
      at three of the nodes of Ranvier delineated by one of the cells. At labelled
      nodes, HRP was of a uniform intensity throughout the nodal axoplasm. Axonal
      labelling gradually diminished along the paranodal regions and was not evident in
      the contiguous internodal axoplasm beyond 20 microns from the node. The myelin
      sheaths, paranodal loops, and axons appeared normal at labelled nodes, and the
      paranodal loops and astrocyte perinodal processes adjacent to those of the HRP
      filled oligodendrocyte unit did not contain HRP. There was no evidence of
      extracellular HRP or tissue damage in the surrounding neuropil, and axons
      neighbouring those enwrapped by the HRP-filled oligodendrocyte did not contain
      HRP. The possibility that axonal labelling was an artefact of either
      iontophoretic injection or tissue preparation is discussed. This provocative
      finding is not definite proof of exchange, but the balance of evidence supports
      the possibility that there was transcellular exchange of HRP at paranodes between
      the labelled oligodendrocyte and some of the axons in the unit. The rarity of HRP
      transfer to axons suggests that it may be a transient or labile event. It is not
      clear whether oligodendrocyte to axon macromolecular exchange has real
      physiological and/or pathological significance.

PMID- 8856333
TI  - An in vitro model of diabetes.

PMID- 8856334
TI  - A novel model for studying lens fiber elongation.

PMID- 8856335
TI  - Efficiency of different lipofection agents in Drosophila S-2 cells.

PMID- 8856336
TI  - Purification of primary human hepatocytes using ricin A chain.

PMID- 8856337
TI  - Epithelial cell line from turbot (Scophthalmus maximus L.)

PMID- 8856338
TI  - Photodynamic effects of protoporphyrin on the cellular level-an in vitro
      approach.
AB  - The purpose of this study was characterizing the phototoxic action of
      protoporphyrin and cellular protection mechanisms, as studied on the cellular
      level. In this process, active oxygen is involved. As a biological system, rat
      hepatocyte short-term and primary cultures were used. Phototoxicity of
      protoporphyrin could be observed, after previous absorption of protoporphyrin to
      membrane structures. Damaging of several cell organelles occurred, such as
      mitochondria and lysosomes. Peroxisomes were not affected. Coated vesicles
      located at the periphery of the cells' interior suggested that protoporphyrin
      absorption is mediated by an active uptake (endocytosis), as well as passive
      diffusion. Lipid peroxidation played a role in protoporphyrin phototoxicity.
      Cellular protection mechanisms such as superoxide dismutase and the scavenger
      glutathione (GSH) protected the cells from active oxygen toxicity. In conclusion,
      protoporphyrin entered the cells by diffusion and endocytosis. Previous
      adsorption to the membrane structures was necessary for the expression of
      protoporphyrin phototoxicity. However, active oxygen itself could not be
      demonstrated. Lipid peroxidation was involved in cell-damaging processes.
      Mechanisms of protoporphyrin phototoxicity on the cellular level were studied.
      Rat hepatocyte primary and short-term cultures proved to be suitable in vitro
      systems for studying biochemical and morphological effects on the cellular level.

PMID- 8856339
TI  - Production of rotenone-inactivating substance(s) by rotenone-resistant insect
      cell line.
AB  - In a previous paper, we showed that a cell line derived from hemocytes of the
      cabbage armyworm, Mamestra brassicae (R-cell) was a thousand times as resistant
      to rotenone as that from ovaries of the same species (S-cell). The S-cells were
      killed by rotenone at concentrations higher than 10(-9) M, while R-cells at
      higher than 10(-6) M. When the R-cells were cultured in the medium containing 10(
      9) M rotenone, the ability of rotenone to kill the S-cells was lost in the used
      medium. Also, when rotenone was incubated in the medium conditioned with R-cells,
      it lost its cell killing activity. It became evident that rotenone-inactivating
      substance(s) were produced in cells and stored in water-soluble form or liberated
      into the medium. The substance(s) were inactivated by heat treatment.

PMID- 8856340
TI  - Isolation and characterization of microvascular endothelial cells from chicken
      fat pads.
AB  - Microvascular endothelial cells from abdominal fat pads of 6-wk-old broiler
      chickens were isolated to provide an in vitro system to study their physiological
      functions. The isolation procedure produced clumps of 10-30 cells, which attached
      to culture vessels in 4 h and attained confluency in 2 wk. At confluency, cells
      had a cobblestone appearance but were not contact inhibited and detached from the
      bottom of the culture vessel 2 wk after reaching confluency. The cells
      internalized acetylated low density lipoproteins, a characteristic of endothelial
      cells. This property was used to obtain pure endothelial cell cultures using the
      cell sorter. When cultured over Matrigel, a reconstituted matrix, the cells
      aligned themselves into chordlike structures and formed branching microvessels.
      Cells plated on type I collagen-coated culture flasks occasionally formed
      chordlike structures and proliferated at a faster rate than cells plated on
      Matrigel. Cells cultured on laminin-coated plates were slender and had long
      cytoplasmic extensions; however, cells cultured on uncoated plastic had
      fibroblastic morphology. These properties are similar to those described for
      microvessel endothelial cells isolated from tissues of other species.

PMID- 8856341
TI  - Angiogenic potential of microvessel fragments established in three-dimensional
      collagen gels.
AB  - During angiogenesis, the microvasculature displays both vessel remodeling and
      expansion under the control of both cellular and extracellular influences. We
      have evaluated the role of angiogenic and angiostatic molecules on angiogenesis
      in an in vitro model that more appropriately duplicates the cellular and
      extracellular components of this process. Freshly isolated microvessel fragments
      from rat adipose tissue (RFMF) were cultured within three-dimensional collagen I
      gels. These fragments were characterized at the time of isolation and were
      composed of vessel segments observed in the microvasculature of fat in situ
      (i.e., arterioles, venules, and capillaries). Fragments also exhibited
      characteristic ablumenally associated cells including smooth muscle cells and
      pericytes. Finally, fragments were encased in an extracellular matrix composed of
      collagen type IV and collagen type I/III. The elongation of microvascular
      elements was subsequently evaluated using morphologic and immunocytochemical
      techniques. The proliferation, migration, and elongation of cellular elements in
      microvessel fragments from rat adipose tissue was dependent on initial fragment
      density, matrix density, and required serum. Inclusion of endothelial cell growth
      factors to microvessel fragments from rat adipose tissue 3-D cultures resulted in
      the accelerated elongation of tube structures and the expression of von
      Willebrand factor in cells constituting these tubes. Molecules with reported
      angiostatic capacity (e.g., transforming growth factor and hydrocortisone)
      inhibited vessel tube elongation. In vitro methods have been developed to
      evaluate numerous mechanisms associated with angiogenesis, including endothelial
      cell proliferation, migration, and phenotypic modulation. Microvascular
      endothelial cell fragments described in this study represent an in vitro
      population of cells that accurately duplicate the in vivo microcirculatory
      elements of fat. The proliferation of cells and elongation of microvascular
      elements subsequently observed in three-dimensional cultures provides an in vitro
      model of angiogenesis. Microvascular formation in this system results from pre
      existing microvessel fragments unlike tube formation observed when cultured
      endothelial cells are placed in three-dimensional gels. This form of tube
      formation from cultured endothelium is more characteristic of vasculogenesis.
      Thus, the formation of microvascular elements from microvessel fragments provides
      the opportunity to examine the mechanisms regulating angiogenesis in an in vitro
      system amenable to precise experimental manipulation.

PMID- 8856342
TI  - The interaction of human fetal neurons and epidermal cells in vitro.
AB  - The interaction of autologous human fetal neurons with epidermal cells was
      studied by culturing fetal dorsal root ganglia (DRG) in the center of a dual
      chamber system with epidermal explants in the outer chamber. The two chambers
      were separated by two concentric stainless steel annular rings adherent to the
      substratum by silicon grease and agarose. Axons from the DRG penetrated the
      agarose barrier, growing into the exterior chamber by 10 d in vitro (DIV) and
      extended past sparse peripheral fibroblasts to interact specifically with
      epidermal cells by 12 to 16 DIV. Scanning electron microscopy (SEM) showed single
      or multiple neuronal fascicles terminating on epidermal cells with spatular,
      veillike or bulbous axon termini. Transmission electron microscopy (TEM) showed
      fine axonal termini between epidermal cells, separated by an intercellular gap.
      The specificity of axonal targeting for epidermal cells rather than fibroblasts
      was also demonstrated by infecting the DRG with Herpes simplex virus type-1 (HSV
      1). Specific anterograde transport of HSV-1 along axons to keratin-expressing
      epidermal cells was demonstrated by immunofluorescence and immunoperoxidase
      staining using monoclonal antibodies to viral glycoprotein D. This model allows
      the study of the mechanism of the specific interactions between neurons and
      epidermal cells analogous to those in fetal development and after cutaneous nerve
      regeneration.

PMID- 8856343
TI  - Regulation of fibroblast proliferation in three-dimensional collagen gel matrix.
AB  - Fibroblasts in vivo reside in a three-dimensional (3-D) matrix. The 3-D culture
      method using collagen gels provides valuable information, but it also has some
      practical difficulties. In particular, the changes caused by the contraction of
      gels and the occasional abrupt detachment from the underlying surface have made
      extended culture difficult. In this study, the 3-D culture method was modified in
      order to observe the cells with minimal change of substrata for longer periods.
      The proliferation characteristics of fibroblasts cultured in gels in response to
      fetal calf serum (FCS), to two defined growth factors, insulin and platelet
      derived growth factor (PDGF), and to a growth inhibitory factor, prostaglandin E2
      (PGE2), were evaluated with this system in comparison with monolayer cultured
      fibroblasts. The DNA content of fibroblasts cultured both in gels and on dishes
      increased in response to FCS in a concentration-dependent manner. The
      proliferation of gel-cultured fibroblasts, however, was lower than that of dish
      cultured cells, and higher concentrations of serum were necessary for
      proliferation. The response of gel-cultured cells to PDGF was also less than that
      of dish-cultured cells. In addition, fibroblasts cultured in gel culture did not
      respond to insulin, while the fibroblasts on dishes responded to insulin in a
      concentration-dependent manner. In contrast to the reduced response to growth
      stimulators, PGE2 inhibited proliferation in gel culture and in monolayer culture
      similarly. The reduced responsiveness to growth stimulation but equivalent
      response to growth inhibition may account for reduced proliferation of
      fibroblasts in 3-D culture.

PMID- 8856344
TI  - Two-dimensional gel analysis of proteins in cell lines from the central nervous
      system of larval Drosophila.
AB  - High resolution two-dimensional gel electrophoresis was used to quantitatively
      analyze the patterns of protein synthesis in three different clones of a nerve
      cell line (ML-DmBG2) of Drosophila melanogaster. When patterns of pulse-labeled
      proteins of the three different clones were compared, I observed quantitative
      variations affecting the rate of synthesis by twofold or more in 25-30% of the
      polypeptides and qualitative differences, always affecting less than 2% of the
      polypeptides. Patterns of protein synthesis were analyzed during the 24 d of
      culture, revealing both quantitative (increase or decrease; 40%) and qualitative
      (presence or absence; 3%) differences. More than 70 proteins synthesized in these
      cultures were secreted into the medium. Among them were two major groups of
      acidic proteins which disappeared with culture time. When cell lines and intact
      central nervous systems were compared, large differences in protein synthesis
      were observed. In fact, only 20% of the synthesized proteins were common to both
      isolated cells grown in vitro and the original nervous system in vivo.

PMID- 8856347
TI  - Varicella-zoster virus. The virus.
AB  - Varicella-zoster virus (VZV) causes chickenpox and herpes zoster. After acute
      infection the virus becomes latent in dorsal root and trigeminal ganglia for the
      lifetime of the individual. The viral genome encodes about 70 proteins, at least
      three of which are thought to be expressed during latency in humans. VZV grows in
      cell culture, but is very cell-associated; it is relatively difficult to obtain
      high titers of cell-free virus.

PMID- 8856345
TI  - Wnt-mediated relocalization of dishevelled proteins.
AB  - The Wnt family of proto-oncogenes encodes secreted signaling proteins that are
      required for mouse development. The Drosophila Wnt homolog, the wingless (Wg)
      segment polarity gene, mediates a signal transduction pathway in which the
      downstream elements appear to be conserved through evolution. One such element,
      the dishevelled gene product, becomes hyperphosphorylated and translocates to the
      plasma membrane in response to Wg (Yanagawa et al., 1995). We report here that
      the mouse Dishevelled-1 (Dvl-1) and Dishevelled-2 genes encode proteins that are
      differentially localized in Wnt-overexpressing PC12 cell lines (PC12/Wnt).
      Whereas Dvl-1 and Dvl-2 proteins are limited to the soluble fraction of parental
      PC12 cells, PC12/Wnt cells display a subset of Dvl-1 protein associated with the
      membrane and Dvl-2 protein with the cytoskeletal fraction. These results suggest
      a conserved role for Dvl in Wnt/wg signal transduction.

PMID- 8856346
TI  - Mycobacterium tuberculosis heat shock protein 10 increases both proliferation and
      death in mouse P19 teratocarcinoma cells.
AB  - Exogenously added Mycobacterium tuberculosis Hsp10, either synthetic or
      recombinant, but not other related heat shock proteins (GroES from Escherichia
      coli or bovine Ubiquitin), increases apoptosis in serum-deprived P19 mouse
      teratocarcinoma cells. The effect is dose-dependent, with a bell-shaped curve and
      peak activity at 10(-9) M (maximal effect: 62.9 +/- 17.7% increase, mean +/- SD,
      n = 10) and is specifically inhibited by a polyclonal antibody raised against the
      synthetic protein. On the other hand, when the same cells are exponentially
      growing, M. tuberculosis Hsp10 increases cell proliferation with a bell-shaped
      dose-response curve and a moderate decrease in potency (peak-activity at 10(-8)
      10(-7) M, with a 43.7 +/- 8.1% increase, mean +/- SD, n = 3). Therefore, it
      appears that this bacterial protein can exert two opposite effects, behaving
      either as a death- or as a growth-promoting factor, depending on the conditions
      of the target.

PMID- 8856348
TI  - The varicella vaccine. Vaccine development.
AB  - In this article, rationales and method of development of attenuated live
      varicella (Oka) vaccine are described, with biologic and biophysical
      characteristics of the vaccine virus. The results of early clinical trials in
      Japan are also described, along with the results of detection of viremia in
      vaccinees and a follow-up of incidence of zoster in acute leukemic children,
      which indicate possible immunopathogenesis of varicella and zoster.

PMID- 8856349
TI  - Pathogenesis of infection with varicella vaccine.
AB  - Because of its exanthem, the disease varicella has been known since antiquity.
      Even late in the 19th century, however, there remained considerable confusion
      between mild smallpox and chickenpox. The name varicella itself is an irregular
      diminutive form of variola. Yet, early in the 20th century, detailed histologic
      studies began to differentiate the exanthems. The investigation of the varicella
      vesicle by Tyzzer 90 years ago remains a classic example (see Fig. 2). Although
      the pathogenesis of varicella vaccine virus infection appears to mimic that of wt
      VZV infection, a vaccine virus-related exanthem is more common in immunized
      children with an underlying immunosuppressive condition, such as leukemia, than
      in normal children. Those immunized children who never develop a rash presumably
      have an abrogated infection in which the host immune response has eliminated the
      virus prior to a major viremic spread. There may be a correlation between the
      presence of an exanthem and the ability of an immunized child to spread the
      varicella vaccine virus. The differences in capsid structure and assembly may
      explain in part the attenuation of the vaccine strain. Because the majority of
      varicella vaccine virus particles in the nucleus have aberrant cores lacking an
      electron-dense center, they are never enveloped. Therefore, they do not become
      infectious virions. In a recent article, Grose et al applied the technique of
      three-dimensional (3-D) computer modeling in an attempt to reconstruct an
      aberrant VZV capsid with the hubcap or pinwheel core. Each 3-D model was then
      sliced by computer to obtain a series of two-dimensional models that represented
      the images commonly seen by traditional electron microscopy. The 3-D model that
      best represented the capsid with a pinwheel core contained particulate matter in
      each of the 12 vertices of the icosahedral capsid (Fig. 14). This model strongly
      suggested that VZV may form in the nucleus an intermediary or end-stage capsid
      with an aberrant distribution of assembly protein or viral DNA within its core.
      Herpes simplex viral particles with pinwheel cores are rarely seen in cell
      culture, so this type of aberrant capsid appears to be associated mainly with VZV
      replication. Thus, the strategy of Takahashi and colleagues to serially passage
      the varicella vaccine virus in human embryonic lung cells, guinea pig embryo
      cells, and Wistar Institute strain 38 (WI-38) cells may have exploited in as yet
      unknown ways the profound cell-associated nature of VZV to achieve an end product
      with attenuated pathogenic potential.

PMID- 8856350
TI  - Assays for antibodies to varicella-zoster virus.
AB  - Anti-varicella-zoster virus serum antibody assays and their use in vaccine
      development are described. Of particular interest are FAMA and neutralization
      assays and the gpELISA. These and other assays are compared and summarized in
      terms of characteristics including biologic relevance, sensitivity, specificity,
      and suitability for different laboratory and clinical applications.

PMID- 8856351
TI  - Immune responses to varicella-zoster virus.
AB  - The host response to VZV is critical to the outcome of primary VZV infection. The
      maintenance of immune memory to the virus is required to prevent symptomatic re
      infection on exogenous re-exposure to VZV and to prevent symptomatic reactivation
      of endogenous virus. Immunization with live varicella (Oka) vaccine elicits
      primary and memory immunity to VZV. Humoral and cell-mediated host responses
      induced by the wild-type virus and by the vaccine strain are comparable, which is
      consistent with the clinical observation that varicella vaccine protects against
      or significantly reduces the clinical symptoms caused by primary VZV infection.
      Widespread use of the varicella vaccine in healthy children will yield further
      knowledge about host-virus interactions, such as the role of exogenous re
      exposure in maintaining persistent immunity, which will be relevant to vaccine
      strategies to prevent other human herpesvirus infections.

PMID- 8856352
TI  - The epidemiology of varicella-zoster virus infections.
AB  - Historically, varicella has been a disease predominantly affecting preschool and
      school-aged children in the United States. The live attenuated varicella vaccine
      was licensed in this country in 1995 and has been recommended for routine use in
      immunization of children 12 to 18 months of age. As an increasing proportion of
      the children in the United States are protected from varicella by vaccination,
      changes in the current epidemiology of the disease are anticipated. This article
      reviews the current epidemiology of VZV infection and outlines issues related to
      possible changes in varicella epidemiology that may follow widespread use of the
      live varicella (Oka) vaccine.

PMID- 8856353
TI  - The varicella vaccine. Clinical trials in immunocompromised individuals.
AB  - A review of the use of live attenuated varicella vaccine in immunocompromised
      children, particularly those with underlying leukemia in remission, is presented.
      Data concerning safety, immunogenicity, and efficacy of this vaccine in high-risk
      children are reviewed. The unique contributions toward our understanding of
      varicella vaccine, including spread of vaccine-type virus, incidence of zoster,
      and immune correlates provided by studies of immunocompromised patients are
      discussed. The importance of protecting high-risk children against severe
      varicella by the use of varicella vaccine is apparent.

PMID- 8856354
TI  - Clinical trials of varicella vaccine in healthy children.
AB  - The Oka varicella vaccine has been tested in clinical trials worldwide in
      thousands of children. Following licensure in Japan, Korea, Germany, and the
      United States, the vaccine has been used in several millions of children. The
      vaccine has been generally well-tolerated with the most common complaints being
      pain and redness at the injection site and a mild rash following vaccination. The
      incidence of herpes zoster has not increased in vaccinees and may have decreased.
      Efficacy rates vary between 65% and 100% depending on the intensity of exposure
      to natural varicella and the potency of the vaccine. In those few vaccinees who
      develop MVLS, the rash is generally milder than seen following natural infection
      (median < 50 versus 300 lesions, respectively, as well as a lower incidence of
      fever). There has been no evidence to date to indicate waning immunity
      postvaccination. Studies are in progress in the United States to evaluate whether
      this will occur and the effect of booster doses of vaccine. It is expected that
      in countries where there is widespread use of the vaccine in healthy children,
      disease rates will fall dramatically as will the morbidity and mortality
      associated with natural varicella in this population.

PMID- 8856355
TI  - Clinical trials of varicella vaccine in healthy adolescents and adults.
AB  - Adolescents and adults have an increased risk of severe and, rarely, fatal
      varicella. Increased risk of exposure of susceptible teens and adults occurs
      because of the more common use of day care and nursery programs, and more common
      exposure of health care workers to herpes zoster. The exposure of susceptible
      parents to their own children represents an important hazard. Live attenuated
      varicella vaccine requires two doses to be adequately immunogenic in adults.
      Safety and clinical tolerability have been well documented, and persistent
      antibody protection from infection and virtual absence of early herpes zoster
      infections are inferred from encouraging preliminary data.

PMID- 8856356
TI  - Modified varicella-like syndrome.
AB  - After incidental exposure to natural varicella, up to 18% of vaccinees reported a
      breakthrough infection known as modified varicella-like syndrome (MVLS) over up
      to 10 years of postvaccination follow-up, compared with natural varicella
      occurring in similarly aged unvaccinated children at the rate of 9% per year.
      Children with MVLS are frequently asymptomatic, and their disease is
      characterized by having fewer lesions, less fever, and lasting fewer days than
      natural varicella. When a case of MVLS occurs there are few secondary cases,
      suggesting that it is infrequently transmitted. Sequelae such as secondary
      bacterial infection, cerebellar ataxia, encephalitis, and pneumonia occur
      infrequently.

PMID- 8856357
TI  - Epidemiologic effects of varicella vaccination.
AB  - For a plausible range of values for the different efficacy characteristics of the
      live varicella (Oka) vaccine at different levels of coverage, modeling results
      suggest that routine immunization of preschool children would greatly reduce the
      number of primary varicella cases, whereas the shift in age distribution of cases
      would not result in increased overall morbidity as measured by number of
      hospitalizations. Although information about some of the vaccine assumptions is
      scanty, the combinations of assumptions leading to an increase in morbidity seem
      unlikely. A catch-up program in older children who have not yet had chickenpox
      will be important. The number and age distribution of the cases in vaccinees are
      sensitive to assumptions about the vaccine, especially the degree and
      distribution of partial protection against infection, relative residual
      infectiousness, and waning of immunity. Responsiveness to boosting by wild-type
      VZV infection was especially important in reducing the number of older cases. The
      advantage conferred by responsiveness to boosting depends on the level of
      transmission. The direct and indirect effects of vaccines and vaccination
      programs interact. Understanding how a vaccine works at the individual level is
      important for the vaccinated individual, but it also influences the overall
      public health benefits of an immunization programs. Lieu et al based a cost
      effectiveness analysis of varicella vaccines on this model of varicella dynamics
      and assumptions about how the vaccines work. Models cannot replace biologic
      understanding. The purpose of such models is not to predict the number of cases
      of varicella, but to examine some possible consequences of introducing a vaccine
      into the routine immunization schedule of preschool children in the United
      States, effects of different vaccination strategies, and the benefits of a
      temporary catch-up program for older children. Modeling exercises of this sort
      force us to formalize our thinking, for instance about the vaccine mechanisms,
      and to admit our uncertainties, such as about the vaccine efficacy assumptions.
      Such models also show where more data need to be collected, for example, on
      boosting and waning of immunity and relative residual infectiousness.
      Improvements in the design of vaccine efficacy studies are necessary to provide
      the input to these models for looking at the long-term effects of vaccination
      programs. Frailty models can be used to analyze the data in the presence of
      heterogeneities in susceptibility. Waning can also be estimated using appropriate
      methods. Relative infectiousness of vaccinees with breakthrough cases can be
      measured by comparing the relative secondary attack rates when the index infected
      person is vaccinated and when the index infected person is unvaccinated. More
      studies are needed to understand how to evaluate responsiveness to boosting.
      Vaccine efficacy studies in the field should be designed to obtain better
      estimates of residual susceptibility, residual infectiousness, duration of
      protection, and the effects of boosting by reinfection with wild-type VZV.

PMID- 8856358
TI  - The varicella vaccine. Prevention of herpes zoster.
AB  - The live attenuated varicella vaccine offers some hope that the frequency or
      severity of herpes zoster might be reduced. Universal immunization with this
      vaccine should result in less latent varicella-zoster virus in dorsal root and
      cranial nerve ganglia than that which occurs following varicella. Moreover, the
      vaccine virus is not well adapted for growth in human cells at normal body
      temperature. Thus, reduced virus for reactivation, and less robust replication,
      may lessen the problem of herpes zoster in vaccinees. For those individuals who
      have already had varicella, the risk of herpes zoster is closely related to the
      loss of varicella-zoster virus cell-mediated immune responses, which decline with
      aging (or immune suppression). In aging individuals these immune responses can be
      enhanced by booster immunization with the varicella vaccine, suggesting that a
      vaccine to prevent herpes zoster is feasible.

PMID- 8856359
TI  - New varicella vaccines.
AB  - The live attenuated varicella vaccine, which is available for the prevention of
      chickenpox, was produced by a classic technology that also has been used for
      polio, measles, mumps, and rubella vaccines. There are many newer technologies
      that have been applied to the research and development of other vaccines. Each of
      these other approaches offers potential advantages and disadvantages relative to
      the current varicella vaccine.

PMID- 8856360
TI  - Chemokines: a superfamily of chemotactic cytokines.
AB  - Chemokines are a bipartite family of chemotactic proteins that bear the
      structural hallmark of four cysteine residues, the first two of which are in
      tandem. The spectrum of action of chemokines encompasses a large number of
      leukocyte populations, including monocytes, granulocytes, lymphocytes, NK and
      dendritic cells. Although the spectrum of action of chemokines largely overlaps,
      clear differences are still present. Chemokines play an important role in the
      recruitment of leukocytes at the site of inflammation, allergic reaction and
      tumors. Available information on receptor usage by MCP-1 and related chemokines
      and signal transduction pathways is reviewed. The better understanding of
      signaling mechanisms will provide a new basis for the development of therapeutic
      strategies.

PMID- 8856361
TI  - Development of Th 1- or Th 2-dominated immune responses: what about the
      polarizing signals?
AB  - Type 1 helper T cells and type 2 helper T cells represent two extremely polarized
      forms of the effector specific immune response, based on a distinctive profile of
      cytokine production. Type 1- and type 2 helper T cell-dominated immune responses
      play a different role in both protection and immunopathology. The differentiation
      of effector phenotypes depends on a complex matrix of interconnecting factors
      resulting from the evolutionary interplay between vertebrates and microorganisms.
      These include the physical form of the antigen, as well as the density and
      affinity of the peptide ligand, the cytokines produced by "natural" immunity
      cells at the time of antigen presentation, costimulatory signals provided by
      antigen-presenting cells, and hormones released into the microenvironment. The
      elucidation of genetic and environmental factors that regulate type 1 or type 2
      helper T cell development in response to different antigenic stimulation is the
      basis for new immunotherapeutic strategies in allergic and autoimmune disorders,
      as well as for the improvement of vaccines.

PMID- 8856362
TI  - Preanalytical factors and the measurement of cytokines in human subjects.
AB  - Cytokines are widely measured in research. However, cytokine analyses are
      influenced by a myriad of factors. For instance, a delay in the separation of
      plasma from cells may lead to a 50% decrease in the concentration of tumor
      necrosis factor in plasma. Another example is the secretion of interleukin-1 beta
      in women which can be twice as high during the follicular phase as in the luteal
      phase. The factors influencing the outcome of these tests can be divided into in
      vivo preanalytical factors (e.g., aging, chronobiological rhythms, diet, etc), in
      vitro preanalytical factors (e.g., specimen collection, equipment, transport,
      storage, etc), and analytical factors. To improve the value of the cytokine
      tests, factors strongly influencing the results have to be controlled. This can
      be done by using standardized assays and specimen collection procedures. In
      general, sufficient attention is not given to the preanalytical factors,
      especially in the measurement of cytokines. This article reviews the
      preanalytical factors which may influence the outcome of these tests in human
      subjects.

PMID- 8856363
TI  - Effect of substance P and its precursor alpha-protachykinin on intracellular free
      calcium concentration in human polymorphonuclear leukocytes.
AB  - The increase in intracellular free calcium concentration is an important step in
      signal transduction leading to phagocyte activation. The undecapeptide substance
      P can influence various functions of human polymorphonuclear leukocytes,
      including chemotaxis, phagocytosis, and respiratory burst. In this study we
      investigated the ability of low-concentration (that can occur in vivo) substance
      P (10(-7) M) and its precursor alpha-protachykinin (3 x 10(-7) M) to increase the
      intracellular free calcium concentration in human polymorphonuclear leukocytes.
      Cells isolated from ten healthy donors were incubated with substance P or alpha
      protachykinin in 1 mM calcium medium for 5 min and the intracellular free calcium
      concentration was monitored using the fluorescent calcium indicator Fura-2am.
      Polymorphonuclear leukocytes from 40% of donors responded to both agonists. The
      substance P- and alpha-protachykinin-induced increase in intracellular free
      calcium concentration was 59 +/- 13 nM and 58 +/- 12 nM and the extracellular
      calcium influx contributed to 87 +/- 8% and 54 +/- 8% of the calcium response,
      respectively. alpha-Protachykinin released almost all the calcium from
      intracellular stores, while substance P mobilized only 24 +/- 5% of this calcium
      pool. Finally, cells that responded to a single challenge with substance P and
      alpha-protachykinin were able to increase their intracellular free calcium
      concentration in response to each of three consecutive stimulations with these
      agonists. This may be an additional mechanism by which substance P and its
      precursor modify the function of human polymorphonuclear leukocytes.

PMID- 8856364
TI  - Phagocyte chemiluminescence in pre-term infants.
AB  - Intact phagocyte function is a pre-requisite for successful defence against
      infection, but paradoxically, these cells may also play a major role in the
      pathogenesis of the infant respiratory distress syndrome. Phagocyte function is
      known to be deficient in pre-term infants, who are at risk of infection as a
      result, but these infants are also at risk of respiratory distress syndrome as a
      result of surfactant deficiency. Despite this, few longitudinal studies of
      phagocyte function have been performed in pre-term infants. We have used
      lucigenin-enhanced chemiluminescence to examine the respiratory burst of mixed
      samples containing polymorphonuclear leucocytes and monocytes of 100 pre-term
      infants at 48- to 72-h intervals during their admission to a neonatal care unit.
      Increased polymorphonuclear leucocyte chemiluminescence was associated with
      respiratory distress syndrome and the use of intermittent positive pressure
      ventilation. Multiple linear regression analysis revealed a slight, but
      significant depression of chemiluminescence in association with the use of
      gentamicin and penicillin when stronger influencing factors such as the presence
      of respiratory distress syndrome were taken into consideration. Measurement of
      phagocyte function by sensitive luminescence assays requires very little blood
      and may be useful in pre-term infants to follow the severity of respiratory
      distress syndrome. However, it is probable that other factors such as antioxidant
      capacity also have an important influence on the degree of tissue damage.

PMID- 8856365
TI  - The role of antioxidants in the prevention of t-butyl hydroperoxide-induced
      chemiluminescence.
AB  - An experimental system which assesses the antioxidant potential of ascorbic acid,
      glutathione, uric acid, and taurine was developed. The system comprised
      hemoglobin, luminol, t-butyl hydroperoxide, and different concentrations of
      antioxidants in TRIS-HCl buffer (pH 7.4). Control assays were performed by
      excluding antioxidants. Chemiluminescence was detected using a liquid
      scintillation counter in single photon mode. All antioxidants, when applied in
      the appropriate concentrations, decreased the maximum chemiluminescence values.
      The minimum concentrations which decreased the chemiluminescence values were
      defined for each of the antioxidants.

PMID- 8856366
TI  - Inhibition of HIV-1 infectivity by low molecular weight heparin. Results of in
      vitro studies and a pilot clinical trial in patients with advanced AIDS.
AB  - Several sulfated polysaccharides have been shown to have anti-HIV activity in
      vitro. However, many of these compounds are not suited for use in vivo because
      they present an increased risk of bleeding or cannot be administered chronically.
      We tested the anti-HIV effects of low molecular weight heparin (LMW-heparin)
      (Enoxaparin) in vitro using a model system of HIV infectivity because LMW-heparin
      can be given to patients on a long-term basis with little risk. In vitro, LMW
      heparin was shown to inhibit HIV-1 production from a T cell lymphoma line (H9)
      and phytohemagglutinin-stimulated lymphoblasts. Inhibition of infectivity was
      dose dependent at concentrations achievable in vivo. We then performed a pilot
      clinical trial in 13 patients with advanced AIDS of 6 months of chronic, self
      administered Enoxaparin given in standard prophylactic doses. CD4 counts appeared
      to stabilize or increase in most patients during the first 3 months of treatment,
      then remained stable or declined after 6 months. There was no appreciable change
      in serum p24 levels. There was no evidence of drug toxicity and no bleeding
      episodes. These findings demonstrate that a commercially available, relatively
      non-toxic form of LMW-heparin is a potent inhibitor of HIV-1 production in
      cultured cells and that it is feasible to treat patients with AIDS with LMW
      heparin on a long-term basis. Definitive clinical trials of LMW-heparins and
      related compounds as experimental anti-viral agents in patients with HIV
      infection are indicated.

PMID- 8856367
TI  - Giardiasis as a cause of hypokalemic myopathy in congenital immunodeficiency.
AB  - Hypokalemic myopathy may occur in several infections. We report a case of severe
      and transient myopathy secondary to hypokalemia induced by chronic intestinal
      infection with Giardia lamblia in a patient with common variable
      hypogammaglobulinemia. Hypokalemic myopathy is documented by serum enzymes,
      electromyography (reduction in the number of voluntarily activated motor unit
      action potentials and an increase in polyphasic motor unit action potentials, and
      pathological changes (hematoxylin-eosin, ATPase staining). The case reported
      involves hypokalemic myopathy induced by giardiasis in a patient with primary
      immunodeficiency; the histopathological changes observed in a skin/muscle biopsy
      from this patient are described for the first time.

PMID- 8856368
TI  - Detection of eight beta-thalassemia mutations using a DNA enzyme immunoassay.
AB  - We describe the use of a polymerase chain reaction-based method followed by a DNA
      enzyme immunoassay for the simultaneous detection of the eight most common beta
      thalassemia mutations in the Mediterranean population. The method is specific,
      sensitive, and easily applicable in routine clinical laboratories for the
      molecular diagnosis of beta-thalassemia patients and at risk couples.

PMID- 8856369
TI  - Lipoprotein(a) after acute exercise in healthy subjects.
AB  - Some acute-phase proteins increase during exercise, and lipoprotein(a) has been
      considered an acute-phase protein on the basis of an increase in its serum level
      after acute cardiovascular episodes or surgery. We found no significant effect of
      acute physical exercise (600 kpm/min for 20 min) on lipoprotein(a) levels in ten
      healthy subjects [pre exercise 6.25 (0.1-14), median (range), mg/dl; at the end
      of exercise 6 (0.1-12) mg/dl; 30 min post exercise 5.9 (0.1-23) mg/dl; 60 min
      post exercise 5.95 (0.1-11) mg/dl]. This suggest that activation of the
      adrenergic system does not induce changes in lipoprotein(a) levels.

PMID- 8856370
TI  - Quantitative risk analysis and the production of microbiologically safe food: an
      introduction.
AB  - There is increasing interest in the application of quantitative risk analysis
      (QRA) in the production of microbiologically safe food products. QRA can be
      defined as a stepwise analysis of health risks which may be associated with a
      particular type of food product, resulting in an estimation of the probability of
      occurrence of negative health effects following the consumption of that food and
      the nature of these risks. Starting with this definition, the following
      successive components can be recognised: (1) hazard identification, which is a
      qualitative indication of the potential microbial hazards that may be associated
      with the consumption of a particular food product; (2) exposure assessment, which
      is the quantitative estimation of the dose of potentially hazardous organisms to
      which the consumer is exposed at the time of consumption of the food; (3) dose
      response assessment, which is the process of obtaining quantitative information
      on the negative effects of different levels of exposure to potentially hazardous
      organisms on the health of the consumer; (4) risk characterization, which
      comprises the activities that are carried out to rank the disorders according to
      severity, perception, economic and social consequences etc., enabling a decision
      to be made about the acceptance of a particular risk; and (5) risk management,
      which is the complex of analyses and judgements to reduce the probability of
      occurrence of unacceptable risks.

PMID- 8856371
TI  - Hazard identification in swine slaughter with respect to foodborne bacteria.
AB  - Swine slaughter is an open process with many opportunities for the contamination
      of the pork carcass with potentially pathogenic bacteria; however, it does not
      contain any point where hazards are completely eliminated. Data on the prevalence
      of various pathogenic bacteria (Aeromonas hydrophila, Campylobacter coli/jejuni,
      Listeria monocytogenes, Salmonella spp., Staphylococcus aureus and Yersinia
      enterocolitica) in pigs, their growth and survival characteristics and ability to
      become established on the slaughter line are presented. The presentation covers
      the processing steps from lairage to chilling and is based on swine slaughter
      practices in Denmark, Norway and Sweden. The major contamination points during
      swine slaughter are pig-related, such as faecal and pharyngeal, and
      environmental. HACCP (Hazard Analysis Critical Control Point) and GMP (Good
      Manufacturing Practice) in swine slaughter must be focused on limiting this
      spread. The pathogenic bacteria show differences in their general mechanism of
      distribution. The major contamination source of Campylobacter spp., Salmonella
      spp. and Y. enterocolitica is the pig, and the contamination of carcasses with
      these bacteria may be limited, provided that only strict slaughtering procedures
      are used. Other organisms such as Aeromonas spp., L. moncytogenes/Listeria spp.
      and S. aureus can be endemic in the processing environment. Since endemic
      bacteria can be controlled by proper cleaning and disinfection, these organisms
      are useful as indicators for the success of GMP rules. The following affiliation
      to CPs or CCPs made for specific steps during slaughter and dressing may serve as
      a guidance: (i) lairage (CP), (ii) killing (CP), (iii) scalding (CP), (iv)
      dehairing (CP), (v) singeing/flaming (CP), (vi) polishing (CP), (vii) circumanal
      incision and removal of the intestines (CCP), (viii) excision of the tongue,
      pharynx, and in particular the tonsils (CCP), (ix) splitting (CP), (x) post
      mortem inspection procedures (CCP) and (xi) deboning of the head (CCP).

PMID- 8856372
TI  - Suggestions for the construction, analysis and use of descriptive epidemiological
      models for the modernization of meat inspection.
AB  - There is consensus that scientifically validated, quantitative assessments of
      actual public health risks are a prerequisite for any sound modernization of
      current meat inspection procedures. This article outlines how such analyses could
      be conducted. Approaches that rely heavily upon extrapolations from theoretical
      dose-effect relationships are inadequate for the assessment of microbiological
      health risks associated with the production and consumption of meat. The use of
      highly structured and very elaborate descriptive epidemiological models covering
      the entire period from stable to table can be considered a promising solution.
      Health risks can be quantified by means of incidence rates and the influence of
      risk factors by means of odds ratios and (population) attributable fractions. A
      great advantage is that when it is not possible to quantify risks exactly, the
      descriptive models are detailed enough to be used in a hazard analysis critical
      control point (HACCP)-like approach and for writing validated codes of good
      manufacturing practice (GMP). There are, however, several conditions which have
      to be met before risk assessment can become the foundation of safety assurances
      for meat, such as active legislative support and the setting up of monitoring
      systems for zoonoses and other health hazards in animals and humans.

PMID- 8856373
TI  - Identification and quantification of risk factors in animal management and
      transport regarding Salmonella spp. in pigs.
AB  - This article discusses the main elements of a descriptive epidemiological model
      for Salmonella spp. in the pre-harvest stages of pork production, and the
      subsequent quantification of risk factors. About two thirds of all Dutch pig
      farms are more or less permanently infected. At infected finishing farms, the
      current probability that Salmonella-free pigs will become infected is about 85%.
      In the case that a certain pen is infected, the current probability that further
      pen-to-pen transmission will occur is about 90% and that (human) vectors will
      also spread the infection 60%. Between 5-30% of the animals may still excrete
      Salmonella spp. at the end of the finishing period, and this percentage can
      double during transport and lairage. In infected pigs at slaughter weight, the
      Salmonella spp. are foremost located in the digestive tract, its contents and the
      closely associated lymph nodes. Under the current circumstances, the lack of farm
      hygiene (odds ratio (OR) 39.7), (re)contaminated feed (OR 1.6), the use of broad
      spectrum antibiotics (OR 5.6), a positive Salmonella-status of animals before
      transport (roughly estimated OR 4.0), the lack of transport hygiene (roughly
      estimated OR 1.1) and transport stress (OR 1.9) are the most important risk
      factors regarding infections with Salmonella spp. Currently the role of on-farm
      contamination cycles with endemic ('house flora') Salmonella spp. is so
      important, that the role of other factors is difficult to ascertain. It is also
      concluded that the farm-phase forms the core of all current problems, and that
      better prevention and control can be achieved by, (i) very strict and consistent
      farm hygiene in combination with promotion of the colonization resistance of
      animals kept together with a prudent use of broad spectrum antibiotics; (ii)
      simultaneous execution of control programmes at breeding farms, multiplying farms
      and finishing farms; (iii) separate transport, lairage and slaughter of the
      animals thus produced.

PMID- 8856375
TI  - Assessment of alimentary exposure to Listeria monocytogenes.
AB  - Survey data on the frequency of foodborne occurrence and dietary exposure to
      Listeria monocytogenes were used to estimate the mininmal mean per person annual
      rate of exposure in the United States during the late 1980s. The estimate was
      restricted to ready-to-eat (RTE) foods because proper cooking was assumed to be
      listericidal. The mean amount of each food type per L. monocytogenes occurrence
      was calculated in about 100 sources, and dietary intake data were used to
      calculate the mean number of occurrences of L. monocytogenes consumption per
      person per year. The mean number of occurrences consumed annually per person was
      determined to be 10 to 100 for RTE food values of 2 to 20% of the total dietary
      intake, respectively. The frequency of foodborne listeriosis (approximately 10(
      5)) was consistent with the estimated exposure rate only if the susceptible
      population was unexpectedly small or extremely high doses were necessary for
      infection. Because little evidence is available to support a high rate of
      unreported non-severe infections, this study was concerned only with severe
      listeriosis cases. Published frequencies of L. monocytogenes concentrations in
      food were used to convert occurrences to colony forming units (CFU). Low L.
      monocytogenes concentrations (approximately 1 CFU/g) were too frequent to be
      responsible for listeriosis in susceptible subjects, would have caused
      listeriosis only with extremely low probability in a one-cell threshold infection
      model. The probability of exposure to a higher dose (> or = 10(3) CFU) was large
      enough to account for the observed rate of listeriosis.

PMID- 8856374
TI  - Application of predictive microbiology to estimate the number of Bacillus cereus
      in pasteurised milk at the point of consumption.
AB  - A procedure is presented to quantitatively estimate the growth of a particular
      organism in a food product during chilled storage using predictive microbiology.
      This results in a quantification of the contribution of every individual process
      step to the total number of organisms, which may be a useful tool to support
      decisions on existing process lines as well as in process and product design. It
      is demonstrated that predictive microbiology will only estimate to within orders
      of magnitude of bacterial growth. This helps to pinpoint the most important
      aspects of a line. The calculations can be helpful to set critical limits and to
      detect hazards by performing 'what if' analyses. The procedure is explained for
      the growth of Bacillus cereus in milk. It is indicated, that with the current
      information, the effect of time/temperature can be estimated. However, to make an
      accurate exposure analysis, more information will be needed.

PMID- 8856376
TI  - Prevalence of shigellosis in the U.S.: consistency with dose-response
      information.
AB  - Every year there are estimated 300000 cases of Shigella in the United States
      (Bennett et al., 1987, Am. J. Prev. Med. 3, 102-114). A beta-poisson model was
      fit to human dose-response information on pathogenic Shigella using the Maximum
      Likelihood Estimation technique (Haas, 1983, Am. J. Epidemiol. 118, 573-582).
      Pooled and separate data sets for the Shigella species were fit to the beta
      Poisson model and 95% confidence limits and regions were calculated. Shigella
      dysentariae and Shigella flexneri confidence regions and limits overlapped with
      each other and with the pooled data set, suggesting that this model can describe
      Shigella in general. The pooled Shigella model as well as the upper and lower
      confidence limits of the three data sets showed average exposures based on the
      estimated U.S. caseload of pathogenic Shigella of 0.01 to 0.014 organisms
      (confidence limits 0.001-0.05) for a 7-day per annum period of exposure and
      ranges from 0.07 to 0.1 organisms (confidence limits 0.006-0.4). for a 1-day per
      annum period of exposure. The plausibility of the pooled dose-response model was
      then evaluated by comparison with two known cruise ship outbreaks. The pooled
      model estimated that the two outbreaks studied could have been due to ingestion
      of 344 (confidence limits 72-915) Shigella cells per meal and 10.5-12 (confidence
      limits 1-44) Shigella cells per glass of water by passengers.

PMID- 8856377
TI  - Assessment of the dose-response relationship of Campylobacter jejuni.
AB  - Mathematical relations describing the risk of infection after exposure to
      enteropathogens are important tools for the evaluation of the potential health
      risk from exposure via food and water. A quantitative description of the dose
      response relation for Campylobacter jejuni with the Beta-Poisson model was fitted
      to experimental data of infection with Campylobacter jejuni (as determined by
      shedding of C. jejuni) obtained in human feeding studies performed by Black et
      al. (1988). The maximum likelihood estimates for the Beta-Poisson model
      parameters based on these data are: alpha = 0.145 and beta = 7.59. The fit of the
      model on the experimental data was good: the difference between the likelihood
      obtained with the Beta-Poisson model and the maximum possible likelihood was not
      significant. The occurrence of symptoms of intestinal illness did not follow a
      similar dose-related trend. Overall, 22% of the infected volunteers developed
      symptoms (diarrhea, fever). The highest illness-to-infection ratio was found at
      an intermediate dose (9 x 10(4)). The dose-response relation and the illness-to
      infection ratio appeared to differ between different C. jejuni isolates. The dose
      response relation derived from feeding studies with a single isolate should
      therefore be considered indicative. The absence of experimental data in the low
      dose range resulted in a relatively large confidence interval at low doses.
      However, in cases where the dose-response relation has been applied so far to
      estimate the health risk of exposure to C. jejuni in water, the uncertainty in
      the dose-response relation was insignificant compared to the uncertainty in the
      exposure estimate.

PMID- 8856378
TI  - Sensitive populations: who is at the greatest risk?
AB  - The purpose of this article was to review the existing literature to define those
      groups of individuals who would be at the greatest risk of serious illness and
      mortality from water and foodborne enteric microorganisms. This group was found
      to include the very young, the elderly, pregnant women, and the
      immunocompromised. This segment of the population currently represents almost 20%
      of the population in the United States and is expected to increase significantly
      by the beginning of the next century, because of increases in life-span and the
      number of immunocompromised individuals. More than half of documented deaths from
      gastroenteritis and hepatitis A illness occur in the elderly in developed
      countries. The overall case fatality ratio for foodborne bacterial
      gastroenteritis outbreaks in nursing homes is 10 times greater than the general
      population. Pregnant mothers suffer from a case fatality ratio from hepatitis E
      infections ten times greater than the general population during waterborne
      disease outbreaks. Enteric diseases are most common and devastating among the
      immunocompromised. Cryptosporidium is a serious problem among patients with
      acquired immuno-deficiency syndrome (AIDS). Cancer patients undergoing
      chemotherapy and transplant patients, are also at significantly greater risk of
      dying from enteric viral infections than the general population. This review
      indicates the need for consideration of enhanced protection for certain segments
      of the population who will suffer the most from food and waterborne pathogens.

PMID- 8856379
TI  - Risk assessment of use of cracked eggs in Canada.
AB  - In 1992, Agriculture and Agri-Food Canada (AAFC) amended its Egg Regulations to
      restrict movement of Canada C eggs (cracks) to federally registered processed egg
      stations for pasteurization. This was questioned by egg producers and some
      provinces on economic grounds. It was also in conflict with long-standing
      practices of marketing eggs in some provinces to retail stores, bakeries,
      restaurants and institutions or at the farm gate. In order to determine how much
      of a risk these eggs were to human health, AAFC requested that the Health
      Protection Branch (HPB) of Health Canada (HC) conduct a risk assessment. On the
      basis of outbreak data, the main hazard in these eggs was identified as
      Salmonella. Salmonellae may occasionally be present on shell eggs even after
      washing, and any Salmonella reaching the membranes can be transferred to an egg
      mixture through breaking, and will rapidly grow under improper storage
      conditions. A Relative Risk analysis showed that cracked eggs are 3 to 93 times
      more likely than uncracked shell eggs to cause outbreaks. A probability of
      illness of 1 in 3800 was derived from the 40 million cracked eggs produced in
      Canada and not pasteurized and the probable 10,500 illnesses arising from these.
      This was for the general population, but this would be greater for those who
      consume many shell eggs or would do so in an unsafe manner, or are more likely to
      be infected (5% of consumers who eat raw or lightly cooked eggs daily, rural
      communities with more opportunities for obtaining cracked eggs, and those who are
      immunocompromised and in institutions). Even though it is not possible to
      precisely determine the risk of salmonellosis through cracked eggs, this
      assessment indicated that there was enough of a concern that a management
      strategy was needed. Eight options for managing the risk were considered and
      ranked for acceptability by both HC and AAFC. Ideally, all cracked eggs should be
      broken and pasteurized, but this is impractical in certain regions of the
      country, and other options, such as sales to food processors operating under Good
      Manufacturing Practices (GMP), and at the farm gate in marked cartons and under
      controlled conditions, were considered to be acceptable, whereas sales to
      institutions and bakeries were not. This is the first fromal food-related
      microbiological risk assessment that HC has completed. Although this is a
      Canadian problem, any country producing eggs has to recognise that despite any
      regulations controlling the use of cracked eggs, economics will dictate that some
      of these will be consumed as whole eggs or egg products, and a management plan is
      desirable to limit hazardous practices associated with these eggs.

PMID- 8856380
TI  - Health risk assessment of Listeria monocytogenes in Canada.
AB  - In this review, the major steps used in the formulation of a health risk
      assessment for Listeria monocytogenes in foods are discussed. Data is given on
      the numbers of human listeriosis cases reported in Canada along with the current
      Canadian regulatory policy on L. monocytogenes. Four major steps in the health
      risk assessment of this organism in foods, namely, hazard identification, hazard
      characterization, exposure assessment and risk characterization, were examined.
      For hazard characterization, since it is known that no direct human dose response
      data is available for L.monocytogenes, a flexible dose response model called the
      Weibull-Gamma model was evaluated. For the exposure assessment, pate and soft
      cheese, both high-risk foods in terms of listeriosis infection, were used as
      prototypes in some of the models that were used. Using disappearance data for
      cheese and 100 g as a typical serving, the data suggested an average of 102
      servings per capita, per year in Canada. As a rough approximation, for L.
      monocytogenes, reference ID10 and ID90 dose levels of response for both normal
      and high risk populations were given as 10(7) and 10(9) for normal individuals,
      and 10(5) and 10(7) for high-risk people. The corresponding dose response models
      were graphically displayed. These models exhibited a higher degree of
      susceptibility and less host/pathogen heterogeneity for the higher risk group.
      The range of doses between the ID10 and ID90 reference values corresponded
      roughly to levels associated with cases of listeriosis. In the risk
      characterization stage, dose response data was combined with some predictive
      growth modeling data of L. monocytogenes on pate, assuming an initial exposure of
      a single cell for food stored at 4 degrees and 8 degrees C. Storage of pate at 4
      degrees C for more than 35 days resulted in a rapidly increasing risk for the
      high risk population, while storage at 8 degrees C produced a similar risk after
      about 13 days. In addition, an equation, used to calculate the average
      probability of acquiring human listeriosis in Canada from soft and semi-soft
      cheese consumption, was formulated. Computations derived from this equation
      indicated a substantial level consistency between reported data and assumptions
      of the risk assessment model. An important part of risk characterization or
      possibly risk management is characterizing the economic and social consequences
      of estimated risks. The total annual estimated cost of listeriosis illnesses and
      deaths in Canada was estimated to be between 11.1 and 12.6 million dollars.

PMID- 8856381
TI  - Incorporation of elements of quantitative risk analysis in the HACCP system.
AB  - Foodborne bacterial diseases cause considerable morbidity and mortality
      throughout the world. Preventive measures such as good manufacturing practices
      (GMP), supplemented by the hazard analysis critical control point (HACCP) system,
      have been introduced as a means of ensuring the production of safe food. However,
      their use does not necessarily provide quantitative information on the risks
      associated with the consumption of a particular food product. To obtain such
      information, elements of quantitative risk analysis (QRA) need to be used. QRA is
      defined as a stepwise analysis of the health risks associated with a specific
      type of food product, resulting in an estimation of the probability of occurrence
      of adverse effects on health following consumption of the food in question. It
      also includes an analysis of the nature of the risks. Taking this definition,
      five successive steps can be recognized: hazard identification, exposure
      assessment, dose response assessment, risk characterization and risk management.
      Food production is a dynamic activity, involving changes in, e.g. the composition
      and microbial quality of raw materials due to seasonal variation. Also, there may
      be continuing changes in processing conditions and in product composition due to
      consumer demands. Therefore, it will be desirable to incorporate QRA in existing
      safety assurance systems, such as HACCP, when sufficient information is available
      to permit this approach.

PMID- 8856382
TI  - Food products and consumer protection: a conceptual approach and a glossary of
      terms.
AB  - There is greatly increased activity in measures being taken to ensure the
      production of safe food. Several concepts, increasingly based on quantitative
      risk analysis, are being introduced and new terminology and definitions are being
      proposed. This article presents a general approach to the production of
      microbiologically safe food and a glossary of appropriate terms. Where possible,
      an attempt is made to provide a more adequate terminology, based on that used in
      risk analysis; background information is also presented.

PMID- 8856383
TI  - Protein concentration of subcutaneous interstitial fluid in the human leg. A
      comparison between the wick technique and the blister suction technique.
AB  - The wick technique and the blister suction technique are the most common methods
      for sampling of subcutaneous interstitial tissue fluid in man. The blister
      suction technique has the advantage of being less invasive than the wick
      technique, but the reliability of this method is still controversial. The aim of
      this study was to evaluate whether the simpler blister suction technique using
      large (8 mm) blisters could replace the wick technique in the investigation of
      patients with postreconstructive leg edema. Fifteen patients with ipsilateral leg
      edema following infrainguinal bypass surgery for lower limb atherosclerosis were
      investigated. The two different fluid sampling techniques were applied
      simultaneously on both legs. The concentration of total protein and albumin as
      well as colloid osmotic pressure of the subcutaneous interstitial tissue fluid in
      the leg were measured in all fluid samples. Agreement analysis was applied to
      compare the two methods, while the correspondence between the methods was
      estimated with linear regression analysis. The agreement index was found to be
      positive for all variables from the operated as well as from the contralateral
      control limb. Furthermore, all values were within the agreement limit. The best
      agreement between the two methods was found for colloid osmotic pressure on the
      operated side. According to the equation of linear regression, there was a slight
      overestimation of the wick values compared to the observed blister values. In
      conclusion, there was a good methodological agreement between the blister suction
      technique and the wick technique. The less invasive blister suction technique
      should be regarded as the method of choice for the investigation of subcutaneous
      interstitial tissue fluid in patients with postreconstructive leg edema.

PMID- 8856384
TI  - Oxygen extraction rates in inflamed human skin using the tuberculin reaction as a
      model.
AB  - The microcirculation of inflamed human skin was assessed non-invasively using the
      techniques of laser Doppler flowmetry, hydrogen clearance flowmetry, visible
      light spectrophotometry and transcutaneous oximetry. Increases in red cell flux
      (from a mean of 1.1 in normal skin to 11.5 V in inflamed skin) and haemoglobin
      saturation (from 49 to 87 and from 38 to 60% with macro- and micro-light-guide
      spectrophotometry, respectively), contrasted with decreases in transcutaneous pO2
      (from 86 to 39 mm Hg). The more intense reactions tended to lead to a lower value
      of oxygen tension at the surface of the skin than the weaker reactions. A barrier
      to oxygen diffusion, presented by the infiltrating inflammatory cells, has
      previously been suggested as the reason for this. The oxygen extraction rate was
      estimated from spectrophotometry and blood flow measurements, using the Fick
      principle, and this showed an increase (from 42 to 130 arbitrary units, AU). When
      the skin was heated to 44 degrees C there was no change seen in this parameter in
      inflamed skin compared with normal skin (from 114 to 133 and from 14.1 to 14.5
      AU), although it tended to increase in the stronger reactions while decreasing in
      the weaker ones. Extraction measured by a cuff occlusion method (with the same
      skin temperature) did show an increase however (from 28 to 57 and from 3.2 to 7.2
      AU), and this was more pronounced in the stronger reactions. It is suggested that
      there may be a critical transit time for a red cell, during which it is able to
      effectively off-load its oxygen. In conditions of very high flow the transit time
      is reduced and oxygen extraction may be compromised further when diffusion is
      already limited.

PMID- 8856385
TI  - Evaluation of two sympathetic cutaneous vasomotor reflexes using laser Doppler
      fluxmetry.
AB  - Disturbances in sympathetic cutaneous vasomotor reflexes may be of pathogenetic
      importance in several microvascular problems. Laser Doppler fluxmetry (LDF)
      enables one to study the influence of sympathetic reflexes on skin blood flow. A
      matter of concern is the high variability of skin blood flow and its reactivity
      to sympathetic reflex test resulting in a poor reproducibility. In this study we
      evaluated two sympathetic stimulation tests, distant cooling and inspiratory
      gasp, and their influence on LDF-measured skin blood flow of the pulp of the big
      toe in 63 healthy volunteers. No age or sex dependency of the LDF test results
      was found. Absolute and relative LDF decrease during distant cooling was highly
      variable between the subjects (LDF decrease, mean +/-SD: 0.7 +/- 5.3%) compared
      to an LDF decrease of 46.5 +/- 3.1% during an inspiratory gasp test. The
      reproducibility, however, was better for the distant cooling test [coefficient of
      variation (CV): distant cooling: 5.8%, inspiratory gasp test: 35.4%]. With the
      use of a thermostatically controlled LDF probe holder fixed at a temperature of
      36 degrees C, the short-term reproducibility of the two sympathetic vasomotor
      tests did not improve, probably because of a steady increase in baseline skin
      blood flow during the test. Surprisingly long-term variability of the percentage
      LDF decrease during the inspiratory gasp test, performed with the heated LDF
      probe, was lower compared to the short-term variability (CV 19.2 vs. 39.0%, p <
      0.05). In conclusion to study sympathetic skin vasomotor reflexes with LDF,
      vasoconstriction during the inspiratory gasp test was more uniform compared to
      the distant cooling test, although the latter was more reproducible. Measuring
      skin blood flow reactivity with a heated LDF probe (36 degrees C) did not improve
      reproducibility.

PMID- 8856386
TI  - Newly developed software for capillary blood pressure analysis in
      microcirculatory research.
AB  - The introduction of the servonulling technique by Wiederhielm in 1963 allowed for
      the first time continuous and dynamic recording of capillary blood pressure (CP).
      In 1979 Mahler used this technique for the first measurements in humans. Data
      analysis was limited to manual analysis of chart recordings. Nowadays fast analog
      digital converters with ay high sampling frequency are used for data recordings,
      and consequently there is a need for an easy-to-use software for data analysis of
      CP data. The presented newly developed computer software allows analysis of mean
      CP, taking into account the zero pressure measured before and after capillary
      cannulation. The simultaneously recorded electrocardiogram R wave is used as a
      marker for the calculation of the mean capillary pulse pressure waves and of
      their characteristic data. This may help determine the significance of the
      capillary pulse waveform for microvascular function. Changes in the pulse
      waveform may be the only detectable difference between patients and healthy
      controls. Analysis of simultaneously recorded temperature, the display of markers
      for valid readings, and the possibility of excluding nonvalid data or artefacts
      from analysis are additional features.

PMID- 8856387
TI  - Impaired microcirculation in heart failure.
AB  - The aim of the present study was to examine the nailfold capillary morphology and
      dynamics in treated chronic heart failure (CHF) in relation to parameters of left
      ventricular structure and function. Twenty patients with CHF class II according
      to the New York Heart Association underwent a capillaroscopic examination at the
      finger nailfold using a computerized videophotometric system (Capiflow) at rest
      and after 1 min arterial occlusion. Study parameters ere number, length and
      diameter of the capillaries as well as capillary blood velocity (CBV). Further
      experiments included echocardiography and determination of left ventricular
      ejection fraction by Tc scintigraphy. Nailfold capillaries in established CHF are
      enlarged and the CBV is dramatically decreased. The reactive hyperemic response
      to 1 min arterial occlusion is attenuated. CBV correlates positively with left
      ventricular ejection fraction (r = 0.61, p = 0.01) and inversely with left
      ventricular end-diastolic (r = -0.56, p = 0.04) and end-systolic (r = -0.69, p =
      0.01) diameters. The time-to-peak flow after 1 min arterial occlusion is
      positively related (r = 0.68, p < 0.05) to the duration of CHF. Our data indicate
      that finger microcirculation in CHF deteriorates as a function of the severity
      and duration of heart failure.

PMID- 8856388
TI  - Serotonin--one possible link between oxygen metabolism and the regulation of
      blood flow in the brain?
AB  - Hyperoxemia is known to alter tissue oxygenation, which in the brain results in a
      scattered and an uneven distribution of cerebrocortical tissue oxygen pressures
      (PtO2). This study examined the effect of ritanserin (a highly specific serotonin
      receptor antagonist, 5-HT2) on the PtO2 distribution during hyperoxemia. The
      measurements of brain oxygenation were performed on the motor cortex in
      anesthetized pigs with a multiwire Clark-type microelectrode. Ritanserin was
      administered (0.035 mg/kg i.v.) during hyperoxemia (inspired oxygen fraction =
      0.70). In 4 of 5 animals, the disturbed oxygenation that was registered during
      hyperoxemia was normalized after the ritanserin injection. These results indicate
      that serotonin may be involved in the regulation of brain oxygenation during
      hyperoxemia, and they also suggest that serotonin may be a link in the coupling
      between the oxygen metabolism and the regulation of blood flow in the brain.

PMID- 8856389
TI  - Suppression of cytokine-induced neutrophil accumulation in rat mesenteric venules
      in vivo by general anesthesia.
AB  - Most studies of neutrophil-endothelial interactions in vivo necessarily require
      the use of general anesthetic agents which are well known to be
      immunosuppressive. By using whole-mount preparations of the rat mesoappendix, we
      were able to study tumor necrosis factor alpha (TNF-alpha) induced neutrophil
      adhesion to the mesenteric venular endothelium in vivo without necessarily using
      general anesthesia. TNF-alpha significantly increased venular-neutrophil
      accumulation in a dose-dependent manner, accumulation was markedly increased at
      1, 2, and 4 h, but returned to baseline after 24 h. After these preliminary dose
      response and time-course studies, we evaluated the influence of standard
      clinically effective doses of several commonly used anesthetic agents
      (thiopental, pentobarbital, ketamine, alpha-chloralose, methoxyflurane, and
      halothane) on the extent of neutrophil-venular accumulation induced 2 h after
      intraperitoneal injection of 0.4 mg/kg TNF-alpha, compared to unanesthetized
      rats. All general anesthetics tested, with the exception of methoxyflurane,
      significantly suppressed this response. In most cases this suppression was
      striking (from 60 to 85%) such that a statistically significant proinflammatory
      response was obscured. Although methoxyflurane also tended to suppress this
      response to TNF-alpha, it was the only agent that allowed the response to be
      clearly seen. Because anesthesia markedly suppresses cytokine-induced neutrophil
      venular adhesion, this model should provide an important complementary technique
      to the classical in vivo microcirculatory approaches which do necessarily require
      general anesthesia.

PMID- 8856390
TI  - Risk factors for childhood obesity in a transitional society in Thailand.
AB  - OBJECTIVE: To identify factors associated with childhood obesity among the
      population of Hat Yai municipality, a transitional society in Thailand. DESIGN:
      Cross-sectional study. SUBJECTS: 2161 primary schoolchildren, aged 6-13 completed
      years. MEASUREMENTS: Weight-for-height of children by measurement, parental
      weight and height, parental income, family history of disease and children's
      activities by questionnaire. RESULTS: Prevalence of obesity was 14.1%. Using
      polytomous logistic regression, statistically significant associations with
      obesity were found for family history of obesity (relative rate ratio, RRR =
      3.1), low exercise level (RRR = 2.6 vs normal), obesity in mother and father (RRR
      = 1.9 and 2.2, respectively vs normal weight status). Significant trends of
      increased risk were associated with higher family income and smaller family size.
      The highest population attributable fraction was that for family history of
      obesity (34%), followed by those for low exercise level (12%) and an obese or
      overweight mother (10%). CONCLUSION: As the parental and family factors
      identified in this study cannot be readily modified, increasing exercise may be
      the most appropriate intervention to prevent obesity in childhood.

PMID- 8856391
TI  - Weight variability and mortality: the Iowa Women's Health Study.
AB  - OBJECTIVE: To evaluate the association between weight variability and risk of
      mortality in women. DESIGN: Prospective cohort study, 1986-1991. SUBJECTS:
      Participants were a population-based sample of 33,760 Iowa women aged 55-69 y,
      free of cancer and heart disease, who completed a mailed questionnaire including
      self-reported weight at ages 18, 30, 40, 50 y, and currently. Weight variability
      was defined by (1) a measure of deviation from the linear regression of each
      woman's five weights on age (the root mean squared error, RMSE) and (2)
      categories of weight gain or loss. MEASUREMENTS: All-cause (n = 1068) and cause
      specific mortality. RESULTS: After adjustment for age and the regression slope of
      weight on age, women who displayed higher weight variability (RMSE) over their
      adult years had an increased subsequent 6-y mortality. The relative risks of
      death for increasing quartiles of RMSE were 1.00 (referent), 1.17, 1.45 and 1.82
      (ptrend < 0.001). Positive linear trends were seen across quartiles of RMSE for
      cardiovascular disease, cancer, and for non-cancer/non-cardiovascular deaths.
      These associations were attenuated increasingly with (1) statistical adjustment
      for body mass index, waist-to-hip ratio, smoking, education level, physical
      activity, alcohol intake, marital status and hormone replacement therapy; (2)
      further adjustment for diabetes and hypertension; and (3) exclusion of women in
      poor or fair health in 1986. Even so, with all adjustments, relative risks of
      coronary heart disease mortality for increasing quartiles of RMSE were 1.00
      (referent), 1.22, 1.63 and 1.67 (ptrend = 0.049). Using the categorical approach,
      age-adjusted risks of death were highest in women who had a large weight loss (>
      10%) or a large cycle of weight change (> or = 10% loss-gain or gain-loss),
      compared with women who had a stable weight (within 5%). Adjustment for
      covariates attenuated these relative risks. CONCLUSIONS: Women who displayed
      greater weight variability in adulthood had an increased risk of dying in later
      life, especially from coronary heart disease. However, to a considerable degree
      this association seems to be due to other unhealthy characteristics and pre
      existing disease among those displaying increased weight variability.

PMID- 8856392
TI  - Influence of insulin on beta-endorphin plasma levels in obese and normal weight
      subjects.
AB  - OBJECTIVE: To establish the possible role of hyperinsulinemia in the elevation of
      plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral
      glucose load. DESIGN: Oral glucose tolerance test (OGTT) and euglycemic
      hyperinsulinemic clamp. SUBJECTS: Two groups of six (age: 22-39 y, BMI: 30-48
      kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and
      five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). MEASUREMENTS:
      Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min
      during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at
      baseline and in steady state condition (i.e. during the last 30 min of insulin
      infusion) in the euglycemic-hyperinsulinemic clamp studies. RESULTS: In the six
      obese patients undergoing the OGTT a significant elevation of beta-EP plasma
      levels was observed between 60 and 90 min after glucose ingestion. In the clamp
      studies no significant differences in beta-EP plasma levels, blood glucose and
      serum insulin were observed between obese and normal weight subjects both at
      baseline and at steady state. A markedly diminished insulin sensitivity along
      with a lower inhibition of C-peptide during insulin infusion was observed in
      obese patients compared to control subjects. CONCLUSION: A rise in serum insulin
      levels unaccompanied by a concomitant increase in blood glucose concentration is
      unable to elicit a beta-EP response in obese patients.

PMID- 8856394
TI  - Genetic influences on central abdominal fat: a twin study.
AB  - INTRODUCTION: Recent studies of regional fat distribution have focused on the
      clinical importance of central abdominal obesity. Central adiposity is strongly
      related to insulin resistance, non-insulin dependent diabetes mellitus (NIDDM),
      dyslipidaemia and cardiovascular disease. While significant genetic influences on
      body mass index (BMI), total body and subcutaneous fat have been demonstrated,
      the inheritance of central abdominal obesity, has not been studied. OBJECTIVE: To
      assess genetic effects on regional fat distribution and associated metabolic
      parameters. DESIGN AND SUBJECTS: We directly measured total body, central
      abdominal (C-abd) and non-abdominal fat using dual energy X-ray absorptiometry in
      50 monozygotic (MZ) and 36 dizygotic (DZ) female twins, of age (mean +/- SD), 44
      +/- 12 and 47 +/- 14 y; BMI 24 +/- 5 and 24 +/- 3 kg/m2; C-abd fat 33 +/- 9 and
      32 +/- 9%, respectively. Total variance in all parameters was independent of
      zygosity and genetic analyses of regional adiposity were performed before and
      after adjusting for age and percentage total body fat. RESULTS: A genetic
      influence was observed on the population variance in total fat, C-abd fat (C-abd
      fat rMZ = 0.66 vs rDZ = 0.20, p = 0.03) and non abdominal fat. After adjusting C
      abd fat for age and total body fat there was a independent genetic influence on C
      abd fat accounting for approximately 70% of the population variance (rMZ = 0.61
      vs rDZ = 0.40, p = 0.001). CONCLUSION: The majority of inter-subject variance in
      central abdominal fat in non-obese individuals is due to genetic factors. The
      inheritance of abdominal obesity, with its associated metabolic consequences, may
      contribute to the familial aggregation of insulin resistance, diabetes and
      cardiovascular disease.

PMID- 8856393
TI  - Use of weight-for-height indices in children to predict adult overweight: the
      Bogalusa Heart Study.
AB  - OBJECTIVE: To compare the body mass index (BMI) (weight/height2) and the Ponderal
      index (PI) (weight/height3) in childhood as predictors of adult overweight in a
      biracial group of children. DESIGN: Prospective, 15-y follow-up. SUBJECTS: 835
      children aged 10-15 y at baseline. MEASUREMENTS: Weight in kg and height in m.
      OUTCOME VARIABLE: Overweight, defined as a BMI greater than 27 kg/m2 in young
      adults. RESULTS: Overall, the BMI and the PI at baseline were identically
      correlated with the BMI at follow-up (r = 0.64, p < 0.001). However, the
      predictions of overweight based on each index were distinctively affected by age,
      sex and race. The probability of adult overweight among 10-year old children was
      greater than 0.5 (50% overweight threshold) if their BMI exceeded 17 kg/m2 in
      black girls, 20 in white girls and 18 in boys of either race. Similarly, the 50%
      BMI overweight thresholds among 15-year-old children were 23 kg/m2 for black
      girls, 25 for white girls and 22 for boys of either race. The 50% PI overweight
      thresholds (in kg/m2) were 12 and 14 for 10-year-old black girls and white girls,
      respectively; and 14 and 16 for 15-year-old black girls and white girls,
      respectively. Among boys, the 50% PI threshold was 13 kg/m3 regardless of age or
      race. CONCLUSION: The BMI and the PI in childhood were both useful in assessing
      sex-and race-specific risks of adult overweight. However, assessments based on
      the Ponderal index were less affected by age and race than those based on the
      BMI, particularly among boys. Hence, to establish general weight goals for
      children, aimed at preventing adult obesity, the PI could be a much better choice
      than the BMI.

PMID- 8856395
TI  - The effect of protein intake on 24-h energy expenditure during energy
      restriction.
AB  - OBJECTIVE: To investigate whether protein intake influences the decline in energy
      expenditure during energy restriction. DESIGN: Cross-over study of three diets of
      4.2 MJ/d for 7 days: one diet with 36% energy as protein and two with 15% energy
      as protein, one high in carbohydrate and the other high in fat. SUBJECTS: Two men
      and six women aged 31-57 y. BMI 27.B-34.1 kg/m2. MEASUREMENTS: 24-h energy
      expenditure (24-h EE), sleeping metabolic rate (SMR) and body weight on days 0
      and 7 of each diet; 24-h urinary nitrogen excretion (24-h UN) on days 0-7 of each
      diet. RESULTS: 24-h EE and SMR declined on all three diets but the decrease was
      significantly less on the high protein diet than on the two low protein diets.
      Weight loss was similar on all three diets. 24-h UN was less than N intake on the
      high protein diet but greater than N intake on the two low protein diets.
      CONCLUSIONS: Maintaining protein intake reduces the decrease in energy
      expenditure during energy restriction.

PMID- 8856396
TI  - Brown adipose tissue temperature in lean and obese rats during exercise.
AB  - OBJECTIVE: To determine the extent to which brown adipose tissue (BAT) heat
      output is influenced by treadmill exercise. DESIGN: The aortic blood core and
      interscapular BAT temperatures were recorded continuously during a short bout of
      intense exercise (different for each rat stock) in a treadmill and the ensuing 1
      h recovery, sampling blood flows at timed intervals. SUBJECTS: Conscious Wistar,
      Zucker lean and Zucker obese rats. MEASUREMENTS: Aortic and interscapular BAT
      temperatures and tissue blood flow. RESULTS: Basal mean temperatures were highest
      for Wistar. Exercise provoked increases in aortic core temperatures in all three
      groups, slowly cooling off during recovery. Exercise and/or fatigue induced
      increases (vs aortic core temperature) of IBAT temperature. The effects were less
      marked in obese rats. CONCLUSION: Increases in BAT temperatures induced by
      exercise were counteracted by parallel decreases in blood flow, resulting in
      insignificant losses of heat from intarscapular BAT during exercise and recovery
      both in lean and obese rats.

PMID- 8856397
TI  - The effects of the inhibition of fatty acid oxidation on pyruvate dehydrogenase
      complex activity in tissues of lean and obese mice.
AB  - OBJECTIVE: To investigate the effects of an acute dose of the fatty acid
      oxidation inhibitor, Etomoxir, on the activity of the pyruvate dehydrogenase
      complex (PDHC) in different tissues in lean and obese mice. DESIGN: An acute dose
      of Etomoxir was given to mice in which obesity had been induced by an injection
      of gold thioglucose and to age-matched controls. The effects of time, dose and
      nutritional state were studied. MEASUREMENTS: PDHC activity in heart, quadricaps
      muscle, liver and white adipose tissue, glycogen content of liver and quadricaps
      muscle, serum glucose and insulin were measured in fed and fasted animals and in
      fasted animals after the ingestion of a glucose load. RESULTS: Etomoxir caused an
      increase in the activity of the active form of the PDHC (PDHCa) in the heart,
      liver and WAT of fed lean mice and in the heart and liver of fed obese mice. In
      fasted mice, increased PDHCa was seen in the heart of lean mice and in the liver
      of obese mice. Etomoxir increased the PDHC response to an oral glucose challenge
      in the liver and WAT of lean mice and in the liver of obese mice. Etomoxir had no
      effect on PDHCa in quadricaps muscle. Serum glucose levels were decreased in
      fasted mice with no change in the fed mice. Etomoxir decreased liver glycogen
      content in both fed and fasted animals and inhibited the accumulation of muscle
      glycogen following the glucose load. CONCLUSIONS: Acute inhibition of fatty acid
      oxidation results in tissue specific increases in PDHCa. Improvements in glucose
      oxidation in tissues other than skeletal muscle may contribute to the improved
      glucose tolerance seen following acute Etomoxir administration.

PMID- 8856398
TI  - Regulation of lipolysis in fat cells of obese women during long-term hypocaloric
      diet.
AB  - OBJECTIVE: To investigate the influence of four weeks treatment with a strictly
      defined very low calorie diet (VLCD) on the regulation of adipocyte matabolism in
      vitro in subcutaneous fat cells of obese subjects. DESIGN: Prospective study.
      SUBJECTS: Nine obese, but otherwise healthy and drug-free women aged 26-48 years
      with BMI 36.4-51.9 kg/m2 were investigated before and during the fourth week on a
      calorie restricted diet. MEASUREMENTS: A subcutaneous adipose tissue biopsy was
      obtained from the abdominal area. Isolated fat cells were prepared and incubated
      in vitro with different agents acting on lipolysis at defined steps in the
      lipolytic cascade. Glycerol (lipolytic index), hormone-sensitive lipase activity
      and incorporation of glucose into lipids were measured. RESULTS: VLCD caused a
      two-fold rise in basal lipolysis (p < 0.005). In spite of this, the maximal
      lipolytic response of noradrenaline, isoprenaline (non-selective beta
      adrenoceptor agonist), dobutamine (beta 1-adrenoceptor agonist), terbutaline
      (beta 2-adrenoceptor agonist), CGP 12177 (beta 3-adrenoceptor agonist), forskolin
      (stimulating adenylyl cyclase), dibuturyl cyclic AMP and 8-bromo cyclic AMP
      (cyclic AMP analogues resistant or sensitive to phosphodiesterase, respectively)
      were maintained. No differences were found in the hormone-sensitive lipase
      activity before or during VLCD. The specific alpha 2-adrenoceptor agonist UK
      14304 was equally effective in inducing antilipolysis both before and during
      calorie restriction. However, during VLCD, the sensitivity and maximal
      antilipolytic effect of insulin were significantly reduced (p < 0.05) and the
      ability of insulin to stimulate lipogenesis was almost completely blunted.
      CONCLUSIONS: Four weeks of VLCD induced elevated basal lipolysis, a resistance to
      the ability of insulin to induce antilipolysis and lipogenesis in subcutaneous
      fat cells, but preserved lipolytic catecholamine action. These are factors that
      together promote fat mobilization and thereby weight reduction during long-term
      calorie restriction.

PMID- 8856399
TI  - Anthropometric equations for estimating abdominal adipose tissue distribution in
      women.
AB  - OBJECTIVES: (1) to develop multiple regression equations for predicting computed
      tomography (CT) derived intra-abdominal (IAF), subcutaneous (SCF) and total (TOTF
      = IAF + SCF) abdominal adipose tissue areas from anthropometric measures and (2)
      to validate the equations. DESIGN: Cross-sectional study. SUBJECTS: 204 healthy
      Caucasian females subjects with a large range of age (17-76 years) and percentage
      body fat (8.8%-48.1%). Fifty-one subjects served as an independent sub-sample for
      the validation of the equations. MEASUREMENTS: Various fatness and fat
      distribution parameters (hydrodensitometry, single CT scan, skinfold and
      circumference measures). RESULTS: Multiple regression equations were developed to
      estimate IAF, SCF and TOTF. R2 for IAF, SCF and TOTF was 0.75, 0.81 and 0.85,
      respectively. The equations were validated on an independent sub-sample of 51
      subjects. All three equations met validation criteria with R2 validations of
      0.79, 0.71 and 0.84 for IAF, SCF and TOTF, respectively. CONCLUSION: These
      equations might be used as an inexpensive estimation of IAF, SCF and TOTF in
      adult Caucasian females varying greatly in age and percentage body fat.

PMID- 8856400
TI  - Role of food familiarity and taste quality in food preferences of individuals
      with Prader-Willi syndrome.
AB  - OBJECTIVE: To investigate the chemosensory function and food attribute
      preferences of individuals with Prader-Willi Syndrome. DESIGN: Cross-sectional,
      matched-groups comparison. SUBJECTS: Fifteen (eight female and seven male)
      individuals with Prader-Willi Syndrome and an age- and sex-matched non-affected
      sample. MEASUREMENTS: Intensity ratings of taste and odor stimuli and hedonic
      ranking of 20 foods varying in sensory attributes (e.g. taste familiarity).
      RESULTS: Sensory test performance was comparable in the PWS and control groups.
      In addition, individuals with Prader-Willi Syndrome showed a pattern of food
      preferences that was similar to their non-affected counterparts. CONCLUSION:
      Abnormal chemosensory function does not underlie the ingestive behavior of
      individuals with Prader-Willi Syndrome.

PMID- 8856401
TI  - Regional body fat distribution in New Zealand girls aged 4-16 years: a cross
      sectional study by dual energy X-ray absorptiometry.
AB  - OBJECTIVE: To measure total body fat content and its regional distribution within
      the body (head, arms, legs and trunk) in young girls and adolescents in relation
      to age and body mass index (BMI). DESIGN: Cross-sectional observational study.
      SUBJECTS: 196 healthy Caucasian girls aged 4-16 years living in an urban town in
      the South Island of New Zealand. MEASUREMENTS: Body weight, height and BMI. Total
      body fat mass (kg) and the regional distribution of this fat (measured by dual
      energy X-ray absorptiometry). RESULTS: All the measured variables, including
      total and % fat mass were higher in older age groups. Regional distribution of
      fat differed, with older girls having a higher proportion of their body fat in
      the trunk and a smaller proportion of their body fat in the heat than younger
      girls. BMI was positively correlated with % trunk fat (r = 0.700) and negatively
      correlated with % leg fat (r = -0.465). Girls with higher levels of adiposity (>
      75th percentile for BMI) stored more fat in the trunk and correspondingly less in
      the legs than girls with lower adiposity (< or = 75th percentile for BMI) at five
      of the six age groups (P < 0.05). CONCLUSION: It is concluded that body fat mass
      increases and shows a more central distribution in young girls as they grow
      older. Increasing adiposity as determined by BMI is associated with an increase
      in fat deposition in the trunk and a decrease in the legs.

PMID- 8856402
TI  - Metabolic indices in relation to body composition changes during weight loss on
      Dexfenfluramine in obese women from two South African ethnic groups.
AB  - OBJECTIVE: To characterize differences in metabolic indices as well as body
      composition in two ethnic groups. SUBJECTS: Eight black and eight white obese
      urban women were studied. DESIGN: Eight black and eight white obse (BMI > 34)
      urban women (BW, WW) were matched for age, BMI, WHR, diet and physical activity
      and investigated before and after 12 weeks of Dexfenfluramine treatment.
      MEASUREMENTS: Anthropometric measurements; Post 75 g OGTT, plasma glucose,
      insulin and C-peptide levels were done. FFA and lactate levels were done at
      onset. Skinfold thickness with Harpenden calipers, bio-impedance for analyses of
      body composition and CT scan for assessment of regional adiposity (at onset and
      after 3 months). RESULTS: In the postabsorptive state the WW had significantly
      higher plasma total cholesterol and triglyceride levels and an unfavourable HDL :
      total cholesterol ratio. Their FFA levels were significantly lower (324 +/- 51 vs
      985 +/- 84 mumol/l; p < 0.0001) and their lactate levels were significantly
      higher (3045 +/- 245 vs 1938 +/- 358 mumol/l; p < 0.001) as compared with the BW.
      During a 75 g OGTT the BW had significantly higher glucose levels at 1 h (8.6 +/-
      0.8 vs 5.1 +/- 0.4 mmol/l; p < 0.005) and 2 h (7.6 +/- 0.6 vs 4.4 +/- 0.3 mmol/l)
      but not at fasting. In contrast the BW had lower insulin concentrations (fasting:
      77 +/- 9 vs 139 +/- 19 pmol/l; p < 0.04 and 1 h 318 +/- 56 vs 624 +/- 75 pmol/l;
      p < 0.005), and C-peptide concentrations (fasting: 400 +/- 99 vs 1600 +/- 99
      pmol/l; p < 0.000 04, 1 h 1400 +/- 433 vs 5966 +/- 333 pmol/l; p < 0.0007 and 2 h
      1266 +/- 333 vs 4066 +/- 366 pmol/l; p < 0.0005). CT scan measurements showed
      that the WW had significantly more visceral fat than the BW (148.5 +/- 2.0 vs
      115.5 +/- 6.9 cm2; p < 0.05) but lost less weight during Dexfenfluramine
      treatment (-4 kg vs -9 kg). Despite this, the WW lost more visceral fat than the
      BW (-27.3 cm2/-18.5%; p < 0.03 vs -15.5 cm2/-13.2%; p < 0.04). In contrast the BW
      had a larger reduction in subcutaneous (SC) fat (-13.9% vs -1.7%; p < 0.01), with
      the greatest reduction in the SC gluteofemoral adipose tissue (widest hip
      circumference -20.8% vs -0.2%; p < 0.001) and mid-femur region (-13.1% vs -0.7%;
      p < 0.08). CONCLUSION: Weight loss in obese black women is associated with a
      major reduction in SC fat mass with the most active mobilization of fat tissue
      occurring in the gluteofemoral area. In contrast the WW had more visceral fat
      that was more readily mobilized. The difference in adipose tissue distribution
      and pattern of mobilization was associated with lower plasma insulin, C-peptide
      and triglyceride concentrations in the BW despite increased FFA and glucose
      levels. These data suggest that plasma insulin concentrations are important in
      regulating differences in regional adipose tissue metabolism as well as the serum
      lipid profile.

PMID- 8856403
TI  - Adiposity and regional body fat distribution in physically active young and
      middle-aged women.
AB  - OBJECTIVE: To test the hypothesis that age does not directly influence body
      composition or regional body fat distribution throughout middle age in women.
      DESIGN: Cross-sectional. SUBJECTS: Thirty female endurance athletes of similar
      competitive ranking ranging in age from 23-56 years. MEASUREMENTS: Body
      composition (hydrodensitometry and skinfolds) and regional body fat distribution
      (waist and hip circumference and tricep, subscapular, suprailiac, abdomen and
      thigh skinfolds); maximal oxygen uptake. RESULTS: In contrast to the age-related
      increases in total and regional body fat levels and decreases in fat-free mass in
      the general population of women, there were no significant trends for changes in
      body composition or regional body fat distribution in our cross-section of highly
      physically active subjects with age. CONCLUSION: These findings suggest that age
      related increases in total body fat and decreases in fat-free mass may be a
      result of reduced chronic physical activity levels with age rather than an
      inevitable consequence of the aging process.

PMID- 8856404
TI  - Male-female differences in the relationship between obesity and
      lipids/lipoproteins.
AB  - OBJECTIVE: To examine the effect of gender on the relationship between obesity
      measures and lipids/lipoproteins. DESIGN: Cross-sectional, matched observational
      study of adult men and women. SUBJECTS: 225 spousal pairs from Cincinnati, Ohio
      (age range, 28-66 years; mean +/- SD (yr), 44.0 +/- 6.7 (men), 42.1 +/- 5.9
      (women). MEASUREMENTS: Body mass measures, lipids, lipoproteins, apolipoproteins,
      physical activity levels, cigarette use and dietary variables. RESULTS:
      Correlations between the lipids/lipoproteins and body mass index (BMI) were
      stronger in women than in men for cholesterol (r = 0.24 vs 0.10), LDL-c (r = 0.27
      vs 0.12), triglycerides (TG) (r = 0.48 vs 0.23) and the ratio cholesterol/HDL-c
      (r = 0.47 vs 0.28). Utilizing statistical regression models which included
      potentially confounding environmental factors, BMI and WHR both contributed
      significant information to describe cholesterol, HDL-c, TG and cholesterol/HDL-c
      values in women, whereas WHR alone provided information for these
      lipids/lipoproteins in men. CONCLUSION: The association between BMI and
      lipids/lipoproteins appears to be stronger in women than in men. In women, in
      contrast to men, BMI and WHR, measures which are easily attainable in the
      clinical setting, provide separate, independent information in the explanation of
      these lipid/lipoprotein levels.

PMID- 8856405
TI  - Waist circumference as a screening measurement for overweight or centrally obese
      Chinese.
AB  - The hypothesis that a single measurement, waist circumference, might be useful to
      identify people at health risk both from being overweight and from having central
      obesity was tested using data on 1513 subjects from a prevalence survey of
      diabetes mellitus in Hong Kong Chinese. It was found that a waist circumference >
      or = 94 cm for men and > or = 80 cm for women identified subjects with high BMI
      (> or = 25 kg/m2), and those with lower BMI but high WHR (> or = 0.95 for men, >
      or = 0.80 for women) with a sensitivity of < 31% and specificity of 100%.
      Decreasing the waist circumference cut-off to 85 cm for men and 75 cm for women
      increased the sensitivity to 79.2% in men and 56.4% in women. It was concluded
      that a single waist circumference measurement did not allow sensitive
      identification of people at health risk from being overweight or from having
      central obesity.

PMID- 8856406
TI  - Binge eating in obesity.
AB  - OBJECTIVE: To investigate the influence of dieting and of body shape
      dissatisfaction on binge eating. DESIGN: Longitudinal study following
      billiopancreatic diversion (BPD), when the body shape has become normal or nearly
      normal, and any worries over weight, dieting and food have probably been
      abandoned completely. SUBJECTS: 65 severely obese patients, evaluated by clinical
      semistructured interview for occurrence of binge eating episodes prior to, and at
      one and at two years following BPD. RESULTS: Whereas preoperative binge eating
      had been reported by 65% of the obese individuals, at two years following BPD
      binge eating occurred only in 9.2% of them. CONCLUSIONS: Weight stabilisation
      following BPD is associated with a sharp improvement in control over food intake,
      and this suggests the central role of dieting and/or of body dissatisfaction in
      causing binge eating episodes.

PMID- 8856407
TI  - Update on genetics of Huntington's disease: availability of direct and accurate
      predictive test.

PMID- 8856408
TI  - Multiple sclerosis and psychiatric disturbances: clinical aspects and a review of
      the literature.
AB  - Psychiatric disturbances during the course of multiple sclerosis (MS) may derive
      from the particular emotional situation induced by a more or less manifest
      awareness of the disease, or be directly attributable to the pathological process
      itself. In this latter case, the range of clinical manifestations is somewhat
      characteristic, as there is often a concomitant impairment of the superior
      nervous functions, particularly those relating to memory and attention.
      Interpretation of the role played by affective disorders is particularly
      controversial, as it is not possible to establish with precision (and the result
      would in any case be a simplistic interpretation of the problem) a direct
      relationship between the sites of cerebral lesions and the psychiatric
      manifestations observed in MS.

PMID- 8856409
TI  - Dermatomal somatosensory evoked potentials in the diagnosis of lumbosacral
      radiculopathies.
AB  - The diagnostic sensitivity of dermatomal somatosensory evoked potentials (DSEPs)
      was evaluated in a homogeneous group of fifteen patients with low back pain due
      to isolated lumbosacral radiculopathy. The normative values from L3 to S1 were
      defined, as were the parameters of abnormality. In seven patients with
      pseudoradicular or referred leg pain, a negative neurological examination and
      images indicative of protrusion or paramedian disc hernia, the DSEPs were normal
      in six cases and slightly altered in one. In eight patients with deafferentation
      leg pain, clinical signs of root damage and images indicative of an
      intraforaminal hernia, the DSEPs showed varying degrees of alteration which could
      generally be correlated to the severity of the clinical picture. This method can
      therefore be useful in differentiating pain due to stimulation of the receptors
      of the osteoarticular structures or the root sheath, in which the DSEPs are
      normal, from pain due to direct root damage, in which the DSEPs are altered. This
      functional evaluation of anatomical damage provides further information which may
      help to achieve a better therapeutic approach.

PMID- 8856410
TI  - Normative data for two neuropsychological tests sensitive to frontal dysfunction.
AB  - Interest in frontal functions has progressively increased over recent years;
      however, despite this, there are only a few "frontal" tasks for which Italian
      normative data are available. The objective of this study was to obtain reference
      values for two frontal tests from a random sample of normal adults: the first
      (the Test of Classification and Recall of Pictures) has been shown to reveal
      selective impairment in patients with unilateral frontal excision; the second
      (the Odd-Man-Out Test) derives from tasks which have been used to evaluate
      frontal functions in animals and detect frontal impairment in Parkinson patients.
      We tested 100 normal subjects, aged 22 to 79 years, stratified by education
      according to the Italian school system. The correction grids for both tests are
      also presented. The usefulness of these tests is represented not only by their
      sensitivity to frontal impairment, but also by the possibility of dissociating
      the various cognitive aspects of frontal lobe dysfunction.

PMID- 8856411
TI  - Transient global amnesia: disease or syndrome?
AB  - Transient global amnesia (TGA) has been defined as the presence of an impairment
      of short-term memory, retrograde amnesia and repetitive queries, without any
      other neurological signs or symptoms. The precise pathophysiology of TGA is
      unclear, although thromboembolic, epileptic, migrainous and metabolic mechanisms
      have been suggested. We have studied the clinical, biohumoral,
      electroencephalographic and neuro-imaging data relating to 25 patients with TGA,
      and found a prevalence of hypertension and hypercholesterolemia. We also found a
      higher incidence of electrical changes in the patients whose TGA was of shorter
      duration, whereas brain CT scans revealed ischemic lesions more frequently in the
      patients with TGA of longer duration. Our findings seem to confirm the hypothesis
      that TGA is a heterogeneous clinical syndrome consisting of pure and ischemic
      forms.

PMID- 8856412
TI  - Prognostic use of ultrasonography in acute non-hemorrhagic carotid stroke.
AB  - In order to evaluate whether the results of ultrasound examination may be
      associated with 30-day outcome, 76 consecutive patients (43 men and 33 women;
      mean age 68.1 +/- 8.9 years) underwent duplex scanning of the carotid
      bifurcations and transcranial doppler investigation of the basal skull arteries
      within the first few hours of the onset of an acute carotid stroke. Forty-three
      patients (56.6%) had appropriate arterial occlusion at ultrasounds examination.
      On day 30, 22 patients (28.9%) were self-sufficient, 41 (53.9%) were disabled and
      13 (17.1%) were dead. The chi-squared test showed that the ultrasound results
      were significantly related to 30-day outcome (p = .0003). After logistic
      regression analysis, the ultrasound results remained independent predictors of 30
      days outcome (p = .0129), together with neurological impairment 24 hours after
      stroke onset and lesion size at control computed tomography. Our study suggests
      that the results of ultrasound examination may be useful in the management of
      acute carotid stroke as an early indicator of patients with a worse prognosis.

PMID- 8856413
TI  - Response variability to ischemic injury in the Mongolian gerbil: an
      electroencephalographic and behavioral study.
AB  - The early effects of 5 or 10 min global cerebral ischemia, sham operation and
      halothane anesthesia were evaluated in Mongolian gerbils by means of
      electroencephalography (EEG), neurological examination and passive avoidance
      training. The "ischemia-sensitive" gerbils (33% and 64% of the 5 and 10 min
      ischemic groups, respectively) died during carotid ligation or within 24 h; the
      "ischemia-resistant" gerbils showed variable behavioral responses. Six hours
      after ischemia, all of the animals presented EEG activity characterized by
      increased delta (1-4 Hz) activity and a decreased theta 2 (6-9 Hz) band, with a
      tendency to recovery at 24 h. Learning impairment was observed in 5 of the 5 min
      ischemic animals (83%) and in 1 sham (17%) and 1 halothane (17%) control.
      Fourteen days after ischemia, histologic damage was observed in 4 ischemic
      gerbils and 1 sham control. On the whole, this study confirms the widely variable
      susceptibility of gerbils to cerebral ischemia. Moreover, although the variable
      effects of carotid occlusion have been attributed to multiple factors involving
      the cerebrovascular system, our data suggest that endogenous cellular mechanisms
      might protect against ischemia. In view of this consideration, it would be useful
      to investigate the molecular causes of the variable cerebral ischemic tolerance
      shown by Mongolian gerbils.

PMID- 8856414
TI  - Evolution of segmental myoclonus during sleep: polygraphic study of two cases.
AB  - We describe the sleep evolution of two cases of segmental myoclonus. The first
      patient had symptomatic palatal myoclonus which, as in most reported cases,
      persisted during sleep with a slight but significant reduction in frequency. The
      second patient presented apparently essential spinal myoclonus, which disappeared
      on falling asleep and recurred for short periods during arousals. This patient
      also had nocturnal myoclonus involving the legs, as well as those muscles
      affected by spinal myoclonus. The physiopathological significance of this unusual
      association is discussed.

PMID- 8856415
TI  - Accidental choke-cherry poisoning: early symptoms and neurological sequelae of an
      unusual case of cyanide intoxication.
AB  - We report the case of a 56-year-old woman who was accidentally poisoned when she
      ingested choke cherries whose pulp contained cyanide, and describe the acute
      clinical picture, the neurological sequelae and the neuroradiological findings.
      After recovery from coma, the patient showed signs of a parkinsonian syndrome,
      retrobulbar neuritis and sensory-motor neuropathy. MRI showed abnormal signal
      intensities involving the basal ganglia. Since no memory deficits were observed,
      we argue that the parkinsonian syndrome was caused by cyanide intoxication rather
      than by subcortical damage due to hypoxia.

PMID- 8856416
TI  - A new case of atypical cerebral dominance.
AB  - A.V., a 73-year-old right-handed man, developed right hemiplegia and hemi
      hypoaesthesia following a cerebrovascular accident. A large, left hemispheric
      lesion was revealed by CT scan but, despite this, the patient did not show any
      language impairment in either Italian or English (which he spoke fluently).
      However, he did show right visual neglect and visuo-spatial deficits, a
      neuropsychological picture that usually follows lesions to the non-dominant
      hemisphere. Given these clinical data, A.V.'s cerebral organisation seems to be
      reversed. This and previous cases reported in the literature are discussed.

PMID- 8856417
TI  - Selective drawing disorders after right subcortical stroke: a neuropsychological
      premorbid and follow-up case study.
AB  - We report the case of a patient affected by a subcortical lesion of the right non
      dominant hemisphere, and demonstrate that he had selective constructional
      disorders by comparing his post-stroke performances with those assessed 18 months
      before the stroke. A detailed analysis was made of the visuospatial, perceptual,
      representational and executive competences involved in drawing tasks at one, two
      and six months post-stroke. Neuropsychological follow-up revealed the progressive
      recovery of all visuospatial abilities. This study provides some interpretative
      elements for constructional disorders and, in particular, for the closing-in
      phenomenon observed only during the subacute phase.

PMID- 8856418
TI  - Acquired dysgraphia with selective damage to the graphemic buffer: a single case
      report.
AB  - We describe one patient with acquired dysgraphia who showed spelling errors
      (mainly deletions and substitutions), both for words and non-words, across all
      output modalities (oral and written spelling, and delayed copying). Spelling
      accuracy was not affected by lexical factors, but was a function of word length.
      The patient's performance in oral and written tasks suggests the hypothesis of
      selective damage to the Graphemic Buffer.

PMID- 8856419
TI  - Role of neurological research in rehabilitation after central nervous system
      diseases.

PMID- 8856420
TI  - Psychosocial stress and anxiety in senile dementia.
AB  - Seventy dementia patients in hospital and two control groups comprising 50
      dementia sufferers in the community and 50 mentally fit elderly people, were
      investigated to determine which social factors such as life events were
      associated with the presence of anxiety symptoms. Very high levels of social
      contact, problems in the patient-carer relationship and high physical dependency
      were all associated with anxiety in the dementia sufferers. Independent severe
      threat life events were associated with anxiety in the dementia patient group.
      Multivariate analyses suggested that this link was mediated by depressive
      symptoms. The results suggest a number of social factors may lead to anxiety in
      dementia sufferers. This has implications for understanding how social factors
      relate to psychopathology in dementia. Clinicians should be more aware of anxiety
      in dementia and consider how social interventions may help reduce and alleviate
      distress.

PMID- 8856421
TI  - Quantitative EEG in the prediction of antidepressant response to imipramine.
AB  - The purpose of this study was to examine the utility of quantitative
      electroencephalography (QEEG) in the prediction of response to imipramine in
      depressed patients. Forty patients with a diagnosis of unipolar depression were
      subjected to a placebo washout and were assessed at pre-drug, 3 h after their
      first dose of imipramine, and again 2 weeks into treatment. Following 4 weeks of
      open imipramine treatment, patients were separated into responder (R) and non
      responder (NR) groups. Statistical analysis of the 29 patients who completed the
      study focused on group comparisons of power spectral estimates in four frequency
      bands from multi-channel recordings. Results showed that theta power
      differentiated R and NR groups prior to treatment, in response to an acute test
      dose, as well as after 2 weeks of active drug treatment. Results based on this
      exploratory study suggest that QEEG may be a useful early predictor of response
      to imipramine.

PMID- 8856422
TI  - Validation of the Edinburgh Postnatal Depression Scale (EPDS) in non-postnatal
      women.
AB  - This paper reports the validation of the EPDS against a Research Diagnostic
      Criteria diagnosis of Major and Minor depression. The EPDS was administered to
      non-postnatal women with older children (mean age of youngest child 3 years 9
      months) and to postnatal women (baby aged 6 months). All who scored 9 or above
      and one third of low scorers were interviewed, using Goldberg's Clinical
      Interview Schedule. The study confirmed good user acceptability of the EPDS when
      administered as a postal questionnaire (92% response rate). The EPDS was found to
      have satisfactory sensitivity (79%) and specificity (85%). Our findings suggest
      that the EPDS take a place alongside other screening scales for depression in
      Community samples. It is proposed that when used in these settings it is referred
      to as the Edinburgh Depression Scale.

PMID- 8856423
TI  - Discriminating depression and anxiety in youth: a role for diagnostic criteria.
AB  - OBJECTIVE: To test the hypothesis that anxiety and depression in youth, as in
      adults, become increasingly discriminable when youth meet criteria for an
      emotional disorder. METHOD: The study uses cross-sectional data at two points in
      time from a large (n = 776) community sample of youths, aged eight to twenty.
      Associations between major depression and five anxiety disorders (overanxious,
      obsessive compulsive and separation anxiety disorders, and social and simple
      phobias) are examined by symptom scale and diagnosis. RESULTS: Anxiety and
      depression are moderately correlated, and substantially comorbid by diagnostic
      category. Symptoms are more discriminable among youths with diagnoses of at least
      one emotional disorder than among those without. A single factor accounts for
      symptoms among the non-diagnosed but multiple factors are required for the
      diagnosed group. CONCLUSIONS: Anxiety and depression are discriminable among
      youth who meet criteria for a specific emotional disorder but more highly
      associated among youths without such a diagnosis. This suggests that in youth, as
      has been shown in adults, depression and anxiety become increasingly
      discriminable as emotional psychopathology becomes more severe.

PMID- 8856424
TI  - Lack of effect of antidepressants on mononuclear leukocyte G-protein levels or
      function in depressed outpatients.
AB  - Evidence from studies in animal and cultured cell models suggests that
      antidepressants (ADs) may enhance postreceptor signalling through the G protein
      coupled adenylyl cyclase (AC) pathways. To test whether this also occurs in
      patients receiving AD treatment, G-protein-activated-AC activity and the levels
      of alpha s and alpha i were measured in mononuclear leukocytes (MNLs) from 12
      subjects with major depressive disorder (MDD) at baseline and after a 5 week
      trial of AD treatment. Although no differences were found in GTP gamma S-and
      forskolin-stimulated AC activity or the levels of alpha s and alpha i in MDD
      subjects compared with age- and sex-matched healthy subjects, pretreatment basal
      AC activity was significantly lower in treatment responders compared with healthy
      subjects. No significant changes were evident in any of these biochemical
      measures following 5 weeks of AD treatment in the patient group as a whole or
      stratified by response. These findings do not support an effect of ADs on the G
      protein AC pathway, at least in MNLs. Lower pretreatment basal AC activity in
      responders suggests some change(s) in post-receptor signalling processes may be
      associated with an increased likelihood of therapeutic response to ADs.

PMID- 8856425
TI  - Counselling of postnatal depression: a controlled study on a population based
      Swedish sample.
AB  - In a two-stage screening procedure using the Edinburgh Postnatal Depression Scale
      (EPDS) at 8 and 12 weeks postpartum and the Montgomery-Asberg Depression Rating
      Scale (MADRS) and DSM-III-R at about 13 weeks postpartum, 41 women identified as
      depressed were randomly allocated to a study and a control group. The women in
      the study group received 6 weekly, counselling visits by the Child Health Clinic
      nurse and the control group received routine primary care. Twelve (80%) of 15
      women with major depression in the study group were fully recovered after the
      intervention compared to 4 (25%) of 16 in the control group. Counselling by
      health nurses is helpful in managing postnatal depression and seems to work well
      within the Swedish Primary Health Care system.

PMID- 8856427
TI  - Relationships of serum insulin-like growth factor II concentrations to growth,
      compositional, and reproductive traits of swine.
AB  - Insulin-like growth factors I and II (IGF-I and -II) are peptide hormones
      involved in metabolic regulation of growth. The objective of this study was to
      determine whether IGF-II concentration was predictive of growth, compositional,
      and reproductive traits of pigs. Forty male and sixty female pigs, divided
      equally between two locations, were weighed at 3-wk intervals from birth to 21 wk
      and bled at 9 and 21 wk of age. At each sampling, two blood samples were
      collected via jugular venipuncture at an interval of at least 1 h. Serum was
      separated and IGF-I, IGF-II, and growth hormone (GH) concentrations were
      determined via RIA. Traits measured included age at puberty and first parity
      litter size for gilts and backfat and longissimus muscle area. Blood was
      collected from a random sample of 52 progeny from 13 litters at 9 wk of age and
      serum was assayed for IGF-II concentrations. Effects of age, sex, location, and
      pig within sex x location on square-root transformed IGF-II concentrations were
      determined by analyzing data as a splitplot. Performance traits were fitted to a
      model including the effects of IGF-II concentration and combinations with IGF-I
      concentration, sex, location, and interactions. Concentrations of IGF-II were
      greater at 9 than at 21 wk of age (226.7 vs 159.3 ng/mL, respectively; P < .001)
      but did not differ between sexes. The correlation between serum IGF-II
      concentrations assayed from samples collected at 9 and 21 wk was .08. The partial
      correlations between IGF-I and IGF-II concentrations were .33 and .14 at 9 and 21
      wk, respectively. The heritability of IGF-II concentration estimated from
      offspring-midparent regression was .08 +/- .20. Nine-week IGF-II concentration
      was positively associated with increased weight from weaning to 12 wk (P < .001).
      However, the sum of 9-wk IGF-I and IGF-II concentrations had a greater
      relationship to weight and gain in the growing phase than the concentration of
      either hormone alone. Concentration of IGF-II at 9 or 21 wk alone did not affect
      backfat thickness, longissimus muscle area, percentage lean, days to 100 kg,
      weight at 21 wk, age at puberty, or litter size. The sum of IGF-I and IGF-II
      concentrations was, however, associated with increased backfat and decreased days
      to 100 kg.

PMID- 8856428
TI  - Lifetime lamb and wool production of targhee or Finn-Dorset-Targhee ewes managed
      as farm or range flock: I. Average annual ewe performance.
AB  - Lifetime (5 yr) lamb production and wool production from 207 straightbred Targhee
      (T) and 474 1/4 Finn-1/4 Dorset-1/2 Targhee (FDT) crossbred ewes managed in a
      range or farm flock system were evaluated for ewe fertility, prolificacy, ewe
      fleece weight, and total lamb weight weaned per ewe exposed. Data included 2,620
      ewe exposures, 2,384 parturitions, 4,638 lambs born, and 3,498 lambs weaned. Ewes
      were born in 1984 through 1987 and lambed the first time as 2-yr-olds. Expressed
      as mean annual values, ewe fertility rates were similar (92.2 vs 91.0%, P = .30)
      for FDT and T ewes. Finn-Dorset-Targhee ewes had higher (P < .001) prolificacy
      (2.11 vs 1.75), weaned more lambs per ewe exposed (1.41 vs 1.18), produced more
      total lamb weight weaned per ewe exposed (33.8 vs 29.9 kg), and lambed 2 d
      earlier than T ewes. Targhee ewes produced more (P < .001) wool (4.5 vs 3.5 kg)
      than FDT ewes. Range flock ewes had a higher (P < .001) fertility rate (94.5 vs
      88.7%), higher number of lambs weaned per ewe exposed (1.38 vs 1.22), and higher
      total lamb weight weaned per ewe exposed (34.7 vs 29.0 kg) than farm flock ewes.
      Farm flock ewes had a higher (P < .001) prolificacy (2.00 vs 1.86) and produced
      more wool (4.2 vs 3.8 kg) than range flock ewes. Targhee ewes had heavier lambs
      at birth (5.2 vs 4.6 kg; P < .001) and at weaning (25.8 vs 25.4 kg; P < .05).
      Range flock lambs were heavier (P < .001) at weaning than farm flock lambs (26.2
      vs 24.9 kg). Lambs from FDT dams had a higher (P < .01) survival rate than lambs
      from T dams (75.6 vs 71.4%). Lamb survival from birth to weaning was higher (P <
      .001) for range flock lambs than for farm flock lambs (76.6 vs 70.4%).
      Incorporation of Finnsheep and Dorset breeding increased the reproductive
      performance in both management systems but decreased wool production.

PMID- 8856429
TI  - Lifetime lamb and wool production of targhee or Finn-Dorset-Targhee ewes managed
      as farm or range flock: II. Cumulative lamb and wool production.
AB  - Cumulative lifetime (five lamb crops) lamb production and wool production of 681
      ewes were evaluated in this study. Lamb production and wool production from each
      ewe at the end of age 2, 3, 4, 5, and 6 yr were added to the previous year's
      production and analyzed within age of ewe. If a ewe failed to lamb, died, or was
      culled, it received a zero for that year and subsequent years. Main effects in
      the model included ewe breed and management system. Per ewe entering the study,
      Finn-Dorset-Targhee (FDT) ewes had a higher (P < .01) number of lambs born (7.42
      vs 5.70), number of lambs weaned (5.39 vs 4.48), and total lamb weight weaned
      (131.7 vs 110.5 kg) than did Targhee ewes. Targhee ewes produced more (P < .01)
      wool (16.1 vs 13.6 kg) than FDT ewes. Range flock ewes had a higher number of
      lambs born (6.74 vs 6.38; P < .05), number of lambs weaned (5.39 vs 4.48; P <
      .01), and total lamb weight weaned (135.8 vs 106.5 kg; P < .01) than did farm
      flock ewes. Farm flock ewes produced more (P < .01) wool (15.2 vs 14.5 kg). A
      second analysis based on only those ewes retained at the start of each subsequent
      breeding season showed FDT ewes had a higher (P < .01) number of lambs born (9.96
      vs 8.11), number of lambs weaned (7.61 vs 6.57), and total lamb weight weaned
      (183.8 vs 165.7 kg) after five lamb crops. Targhee ewes produced more (P < .01)
      wool (22.5 vs 17.6 kg). Farm flock ewes had a higher (P < .10) number of lambs
      born (9.18 vs 8.89) and produced more (P < .01) wool (21.1 vs 19.0 kg) than range
      flock ewes. Range flock ewes weaned more (P < .05) lambs (7.27 vs 6.92) and had
      more (P < .01) total lamb weight weaned (184.3 vs 165.2 kg) than farm flock ewes.

PMID- 8856430
TI  - Influence of steroid implants and concentrate feeding on performance and carcass
      composition of cull beef cows.
AB  - Sixty nonpregnant, mature beef cows were used to evaluate the influence of
      steroid implants on performance and carcass composition of beef cows fed a high
      concentrate diet. Twelve nonfed cows were slaughtered at 0 d. Remaining cows were
      stratified by weight and randomly assigned to an implant treatment and feeding
      period (28 or 56 d). Treatments included 1) no implant (control), 2) a 200-mg
      trenbolone acetate (TBA) implant, 3) a 200-mg testosterone propionate +20 mg of
      estradiol benzoate (TEB) implant, or 4) both implants (TBA + TEB). As days on
      feed increased, hot carcass weight (HCW), carcass soft tissue (CST) weight,
      adjusted fat thickness (AFT), longissimus muscle area (LMA), percentage of CST,
      and percentage of CST lipid increased (P < .05) and percentage of CST crude
      protein and moisture decreased (P < .05). Cows fed for 56 d accumulated (P < .05)
      more kilograms of lean than cows fed for 28 d, and cows fed for 28 d tended (P =
      .08) to have more kilograms of lean than nonfed cows. Cows fed for 56 d had (P <
      .05) higher dressing percentages than nonfed cows or cows fed for 28 d, and
      nonfed cows had (P < .05) higher dressing percentages than cows fed for 28 d.
      Implanted cows compared with control cows had (P < .05) heavier final weights,
      increased gains, improved feed efficiency, heavier hot carcass weights, larger
      LMA, higher cutability yield grades, compositionally leaner CST (higher
      percentage of moisture and protein and lower percentage of lipid), and more
      kilograms of lean. In addition, double-implanted (TBA + TEB) cows had (P < .05)
      more kilograms of CST than control and TBA-implanted cows. Furthermore, cows
      implanted with TBA had (P < .05) lower dressing percentages than TEB-implanted
      cows, less AFT than controls, and fewer kilograms of lipid than cows on the other
      three treatments. Full feeding of thin beef cows for 28 or 56 d increased carcass
      weight through an increase in CST lean as well as fat (lipid). The live
      performance and accretion of lean during realimentation can be enhanced by using
      anabolic implants.

PMID- 8856431
TI  - Influence of steroid implants and concentrate feeding on carcass and longissimus
      muscle sensory and collagen characteristics of cull beef cows.
AB  - Sixty nonpregnant, mature beef cows were used to determine the effects of steroid
      implants and concentrate feeding on carcass quality, longissimus muscle (LM)
      collagen characteristics, and LM sensory traits. Twelve nonfed cows were
      slaughtered at 0 d to establish basal carcass values. The remaining 48 cows were
      assigned randomly in a 2 x 4 factorial arrangement to an implant treatment and
      fed for either 28 or 56 d. The implant treatments were 1) nonimplanted
      (controls), 2) a 200-mg trenbolone acetate (TBA) implant, 3) a 200-mg
      testosterone propionate +20 mg estradiol benzoate (TEB) implant, or 4) both
      implants (TBA+TEB). Carcasses from cows fed for 28 and 56 d had improved (P <
      .05) LM marbling, lean maturity, and quality grade; a lighter (P < .05) LM color
      (higher Hunter L* values); a higher (P < .05) percentage of LM soluble (heat
      labile) collagen; and a lower (P < .05) LM Warner-Bratzler shear force value
      (more tender) than carcasses from nonfed cows. Feeding for 28 and 56 d also
      improved (P < .05) LM sensory panel traits of flavor intensity, connective tissue
      amount, myofibrillar tenderness, and overall tenderness. Feeding cows for an
      additional 28 d (to 56 d) improved (P < .05) LM visual lean color, texture, and
      firmness and carcass fat color. All LM HunterLab color measurements were higher
      (P < .05) for cows fed for 56 d compared to 28 d, indicating a brighter, redder,
      more vivid color. Implant treatments did not influence (P > .05) carcass quality
      or LM color. Steaks from implanted cows compared to controls had (P < .05) more
      soluble (heat-labile) collagen, a higher percentage of soluble collagen, and
      improved sensory traits of tenderness (myofibrillar and overall) and connective
      tissue amount. Steaks from TBA-implanted cows compared to the other implant
      treatments had superior (P < .05) LM sensory evaluations for myofibrillar and
      overall tenderness. Feeding thin cows a high-concentrate diet for 28 d improved
      quality grade and LM sensory traits, and feeding for 56 d improved LM lean and
      carcass fat color. Implanting fed cows improved LM sensory panel tenderness.

PMID- 8856432
TI  - Characterization of DNA polymorphisms in three populations of hereford cattle and
      their associations with growth and maternal EPD in line 1 herefords.
AB  - Three populations of Hereford cattle differing in inbreeding levels and genetic
      potential for growth were genotyped for seven DNA polymorphisms. The populations
      were compared to determine differences in allele frequency and genetic variation.
      Significant differences in allele frequency among the populations were found at
      six of the seven polymorphisms genotyped, and average genetic variation differed
      as expected when inbreeding levels were considered. Effects of several
      polymorphisms on growth and maternal EPD were evaluated for one population (Miles
      City Line 1 Herefords) using regression analysis. Substitution of a B allele for
      an A allele of the kappa-casein polymorphism accounted for significant decreases
      in direct birth weight and maternal 180-d gain from birth to weaning EPD
      explaining 15% and 8%, respectively, of EPD variability. Several other
      significant effects accounting for small portions of EPD variability were also
      detected.

PMID- 8856433
TI  - Systematic error in genetic evaluation of miles city line 1 hereford cattle
      resulting from preadjustment for age of dam.
AB  - Differences in preweaning growth of calves nursing 2- and 3-yr-old dams compared
      with contemporaries nursing older dams are accentuated in the Miles City Line 1
      Hereford herd relative to age-of-dam (AOD) effects implied by preadjustment of
      205-d weight in national cattle evaluation. Mixed-model analyses of 205-d weight
      that fit random individual direct effects and maternal genetic and permanent
      environmental effects on 4,998 calves were conducted to 1) determine the
      magnitude of residual AOD effects after preadjustment (PA) using industry
      standard procedures and 2) compare changes in genetic predictions resulting from
      either PA or simultaneous adjustment (SA) for AOD. Expressed as differences from
      the 5- to 10-yr-old age effect, simultaneously estimated AOD effects were 45 +/-
      1, 19 +/- 1, 6 +/- 1, and 19 +/- 3 kg for 2, 3, 4, and 11+ AOD classes,
      respectively. Comparable estimates of residual AOD effects after PA were 20 +/-
      1, 6 +/- 1, 1 +/- 1, and 14 +/- 3 kg. Rank correlations of direct (BVd) and
      maternal (BVm) breeding values (BV) for 205-d weight from the analysis using PA
      with BV predicted using SA for AOD were .98 and .77, respectively. Estimated
      genetic trends were also affected by the method of accounting for AOD effects.
      One hundred fifty replicate simulations of 205-d weights with pedigree, fixed
      effect, and variance-covariance structures corresponding to the experimental
      population were used to establish correlations (r) of predicted BV with
      underlying true values. The r of predicted BVd with true values were reduced less
      than .02 by PA compared to SA in accounting for AOD. However, r of predicted BVm
      with true values were reduced more than .13 by PA compared to SA in accounting
      for AOD. These data indicate potential for systematic error in genetic
      evaluations that apply standard adjustments for AOD to 205-d weight.

PMID- 8856434
TI  - Direct and maternal genetic covariances by age of dam for weaning weight.
AB  - Weaning weights of calves of dams at ages in years of 2, 3, and older were
      modeled to be three separate traits. Fixed effects were sex of calf-year of birth
      combinations for nine pure breeds and sex of calf-year of birth-generation for
      three composite populations. Random effects fitted for each trait were correlated
      direct and maternal genetic, maternal permanent environmental, and temporary
      environmental. Direct and maternal effects were correlated across traits. A
      multiple-trait, derivative-free REML algorithm was used to estimate the 30
      (co)variance components. Number of animals per breed group ranged from 1,244 to
      4,326. For the three traits for pure breeds, average proportions of phenotypic
      variance were .34, .31, and .27 for direct genetic; .16, .15, and .12 for
      maternal genetic; and .18, .20, and .17 for maternal environmental effects.
      Average correlations among the three traits were .84 for direct genetic, .78 for
      maternal genetic, and .71 for maternal environmental effects. Average of direct
      maternal genetic correlations for pure breeds was .05. For the composite breeds,
      average proportions of phenotypic variances were .44, .46, and .36 for direct
      genetic; .06, .06, and .05 for maternal genetic; and .16, .14, and .14 for
      maternal environmental effects. Average correlations among the three traits were
      .93 for direct genetic, .76 for maternal genetic, and .85 for maternal
      environmental effects. Average direct-maternal genetic correlation was .09 for
      composites. No evidence was found for greater direct-maternal genetic correlation
      for earlier than for later ages of dam. Sign and magnitudes of direct-maternal
      genetic correlations seemed to differ among pure breeds and were reflected in
      composites from those parent breeds.

PMID- 8856435
TI  - Adrenocorticotropic hormone dose response and some physiological effects of
      transportation on pregnant Brahman cattle.
AB  - The appropriate dose and the ability of exogenous ACTH to mimic the physiological
      effects of a real stressor need to be determined. In Exp. 1, 25 pregnant Brahman
      heifers were injected i.v. with either 0 (saline), .125, .25, .5, or 1 i.u. of
      ACTH/kg BW. Plasma cortisol was determined in blood samples collected during a 5
      h period, and an integrated cortisol response was calculated for each cow. The
      greater the dose of ACTH, the greater was the integrated cortisol response (P <
      .001). However, peak plasma cortisol in response to the four doses of ACTH did
      not differ (P > .6). The plasma cortisol concentrations returned to baseline more
      slowly in those cows receiving the greater doses of ACTH, making their integrated
      areas of response greater. In Exp. 2, pregnant Brahman cows were either
      transported 48 km (n = 28), injected with 1 i.u. of ACTH/kg BW (n = 21), or
      served as shams (n = 28). Each treatment was repeated at 60, 80, 100, 120, and
      140 d of gestation. Shrink was greater for the transported cows than for either
      the ACTH-treated or sham cows, 14.3, 6.0, and 5.2 kg (P < .001). Shrink also
      decreased in response to each subsequent application of treatment for all three
      treatment groups (P < .001). Transported cows had lower plasma cortisol
      concentrations after the first two applications of treatments (P < .006). The
      range of doses of ACTH caused a similar peak cortisol release; however, it took
      cortisol longer to return to baseline as ACTH dose increased. Repeated
      administration of exogenous ACTH did not cause the same amount of shrinkage as
      transportation, and the resultant cortisol concentrations remained consistent for
      each administration. There was no apparent carryover effect of repeated
      administration of ACTH at 20-d intervals. Maximal plasma cortisol concentrations
      in Brahman cattle can be obtained with doses of ACTH much smaller than those
      traditionally injected. However, larger doses of ACTH maintained plasma cortisol
      concentrations for a longer duration. Repeated transportation caused a decrease
      in cortisol release and shrinkage indicative of psychological habituation.
      Injections of ACTH did not cause the same physiological response as
      transportation.

PMID- 8856436
TI  - Patterns of nutrient interchange and oxygen use among portal-drained viscera,
      liver, and hindquarters of beef steers from 235 to 525 kg body weight.
AB  - Our objective was to quantify changes in supply and use of nutrients and O2 by
      large-frame, multicatheterized beef steers as they grew from 235 to 525 kg BW.
      Steers consumed 5.25 to 9.87 kg DM/d of a 62% concentrate diet that provided 126
      to 217 g N/d and 1 kg ADG. Steers were assigned to three groups (eight, nine, and
      eight steers each) that divided the BW range into thirds. Weights at first
      sampling for the three groups were 236, 319, and 445 kg, respectively. Each group
      was sampled twice. Groups were killed after the second sampling. Tissue weights
      and hindquarters (HQ) contents of fat, protein, and ash were measured. Blood
      flow, oxygen uptake, and net uptake or release of metabolites were regressed
      against functions of BW.75 to assess changes during growth. Blood flow in all
      tissues except liver and oxygen use by all tissues decreased per unit tissue
      weight as BW.75 and age increased. Changes with age per unit liver weight were as
      follows: decreased uptake of propionate and lactate, increased uptake of alpha
      amino N and glutamine, decreased production of urea and glutamate, and increased
      production of acetate and beta-hydroxybutyrate. Glucose and urea production per
      unit liver weight was constant. Changes with age per unit HQ weight were as
      follows: increased uptake of glucose, decreased uptake of alpha-amino N and
      glutamate, decreased release of lactate, and increased release of glutamine.
      Weight of the portal-drained viscera (PDV) increased from 91 to 97 g/kg EBW as BW
      increased from 236 to 522 kg; PDV fat increased from 375 to 552 g/kg PDV tissues.
      Liver decreased from 16 to 12 g/kg EBW. Hindquarters decreased from 286 to 266
      g/kg EBW; HQ protein was 200, 197, and 200 g/kg HQ tissue for Groups 1, 2, and 3,
      respectively. Corresponding fat was 131, 182, and 177 g/kg HQ tissue. Changes in
      net flux reflect changes in nutrient partitioning and tissue deposition as steers
      grew and aged.

PMID- 8856437
TI  - Effects of growth hormone administration and dietary protein intake on insulin
      like growth factor I and growth hormone receptor mRNA Expression in porcine
      liver, skeletal muscle, and adipose tissue.
AB  - The effects of growth hormone (GH) and dietary protein on expression of IGF-I and
      GH receptor (GHR) genes in liver, muscle, and fat of pigs were investigated.
      Forty-eight intact male Large White x Landrace pigs were allotted to eight
      treatment groups (four diets with or without GH). The pigs were restriction-fed
      one of four diets, which differed only in their protein content (9.9, 13.1, 16.2,
      and 19.4%, as-fed basis), for a total of 3 wk. The pigs were then injected
      intramuscularly with either porcine GH (50 micrograms.kg-1.d-1 of rpST) or
      vehicle for the last 7 d. Pigs were slaughtered 4 h after the final injection.
      Total RNA was extracted from all tissues and then RNase protection assays were
      performed to measure expression of IGF-I and GHR genes. Expression of IGF-I mRNA
      was found to be GH responsive in the liver, semitendinosus (ST), and adipose
      tissue (P < .01) but not in longissimus muscle (LD). Dietary protein increased
      IGF-I expression only in the adipose tissue (P < .01). Expression of class 2
      transcripts of IGF-I were observed only in the livers of GH-treated pigs, with no
      effect of dietary protein. Expression of GHR mRNA was found to increase with GH
      administration in liver and skeletal muscle (LD and ST, P < .05) but not in
      adipose tissue. There were diet x GH interactions on GHR expression in liver, ST,
      and adipose tissue, resulting in the highest GHR expression being in the high
      protein-fed, GH-treated group for liver, but in the low protein-fed, GH-treated
      group for muscle and adipose tissue. This study demonstrates tissue-specific
      control of expression of the two genes and also tissue-specific promoter usage
      (IGF-I exon 2 in liver) in response to GH administration.

PMID- 8856438
TI  - Effects of blast chilling and postmortem calcium chloride injection on tenderness
      of pork longissimus muscle.
AB  - Two studies were conducted to evaluate the effects of blast chilling of carcasses
      and injection with calcium chloride (CaCl2) at 24 h postmortem on Warner-Bratzler
      shear values (WBS) and moisture losses of pork longissimus muscles (LM). In a
      preliminary study, Exp. 1 was conducted to determine whether the injection
      procedure using 100% water had an influence on WBS of pork LM. Injecting pork LM
      with water at 24 h postmortem had no effect on WBS (P = .64). In Exp. 2, 27
      carcass sides were assigned to 1) blast chilling for 1 h at 25 degrees C and then
      chilling for 23 h at 1 degree C or 2) standard chilling for 24 h at 1 degree C.
      At 24 h postmortem, the LM was removed from each side and divided into anterior
      (AL) and posterior (PL) halves. For each LM, the CaCl2 treatment was assigned
      randomly to either the AL or PL. Those receiving CaCl2 were injected with a .3 M
      solution at 10% by weight. Muscles then were stored for 3 d at 1 degree C before
      2.54-cm chops were removed, cooked to an internal temperature of 70 degrees C,
      and allowed to cool for 2 h, then six 1.27-cm cores were taken and sheared. No
      differences (P > .05) in purge or cooking loss were observed, but rapid chilling
      reduced (P < .05) the combination of purge and cooking loss without influencing
      WBS (P = .77). The injection of CaCl2 at 24 h postmortem lowered (P < .05) WBS of
      pork LM muscle. Therefore, the tenderness of pork can be enhanced by injection of
      CaCl2.

PMID- 8856439
TI  - Effect of vitamin C concentration and co-injection with calcium chloride on beef
      retail display color.
AB  - The objectives of these experiments were to determine 1) the most effective
      vitamin C concentration to stabilize color of beef cuts during retail display and
      2) the effect on color of incorporating vitamin C into a calcium chloride (CaCl2)
      injection solution. Top round cuts (semimembranosus and adductor) were injected
      with 5% by weight of a 0, .25, .5, 1, 2, or 4% sodium ascorbate solution (Exp. 1)
      or a 0, .5, 1, or 1.5% sodium ascorbate solution (Exp. 2). In Exp. 1, vitamin C
      resulted in more (P < .05) stable lean color during 9 degrees C display, and .5,
      1, and 2% vitamin C were most (P < .05) effective. In Exp. 2, all concentrations
      of vitamin C maintained redder (P < .05) steaks after 3, 5, and 7 d of display
      than control steaks and had a lower (P < .05) percentage of surface discoloration
      after 5 and 7 d of display at 1 degree C. Experiment 3 used beef bottom round
      cuts (biceps femoris) to compare control, vitamin C- (1%), CaCl2-(200 mM) and
      vitamin C + CaCl2-treated steaks displayed at 1 degree C. Calcium chloride
      treated steaks were more (P < .05) brown and had a higher (P < .05) percentage of
      surface discoloration on d 5 and 7 than control steaks, whereas steaks treated
      with vitamin C or vitamin C + CaCl2 were more (P < .05) red and had lower (P <
      .05) discoloration on d 5 and 7 than control steaks. Vitamin C can be injected
      into beef subprimals to enhance lean color stability and extend retail display
      life. Vitamin C also can be used in combination with CaCl2 to offset potential
      color deterioration, after 5 d of display, due to salt-induced oxidation.

PMID- 8856440
TI  - Effect of halothane genotype, breed, feed withdrawal, and lairage on pork quality
      of belgian slaughter pigs.
AB  - A total of 434 Belgian Landrace (B) or Pietrain x B (PB) pigs, of known halothane
      genotype (NN, Nn, and nn), were slaughtered in a commercial abattoir. Pigs were
      either fed until loading or deprived of food overnight before delivery. Upon
      arrival at the abattoir, pigs were slaughtered after different lairage times
      (within 1 h after arrival, after 2 to 3 h lairage, or 4 to 5 h lairage). Meat
      quality traits were measured on the carcass, as well as on a piece of loin.
      Halothane genotype was the predominant factor determining meat quality traits
      related to the PSE condition (P < .001 for pH 40 min after death, internal
      reflectance, color L value; P < .01 for drip losses, transmission value). For
      these traits, nn pigs were always significantly different from Nn and NN pigs.
      Depending on the specific trait, Nn pigs were intermediate between NN and nn
      pigs, or close to NN pigs. For pH 40 min after death and drip losses, Nn and NN
      pigs were significantly different, whereas the difference between Nn and NN pigs
      was not significant for internal reflectance, color L value, and transmission
      value. Shear force and intramuscular fat content were apparently not related to
      the PSE condition and were not influenced by the halothane genotype (P > .05).
      Differences in meat quality between B and PB pigs and between gilts and barrows
      were rather unimportant compared with the effect of halothane genotype. Overnight
      feed withdrawal had no effect on meat quality (P > .05 for all PSE-related
      traits). On the other hand, holding pigs a few hours in lairage improved meat
      quality compared with immediate slaughtering (P < .05 for pH and temperature in
      the loin 40 min after death, internal reflectance, color L value, transmission
      value, drip losses). This effect was more pronounced in stress-susceptible pigs
      than in stress-resistant pigs.

PMID- 8856441
TI  - Prediction of live lamb chemical composition utilizing electromagnetic scanning
      (ToBEC).
AB  - Electromagnetic scanning was investigated to determine its accuracy in predicting
      chemical composition in live lambs. Forty-seven Rambouillet wether lambs were
      scanned with an electromagnetic instrument (ToBEC Model HA-2). Lambs were
      serially scanned and slaughtered over the weight range of 29.5 to 63.5 kg. Each
      lamb was scanned twice: before and immediately after 24 h of food deprivation.
      Chemical composition was determined from whole-animal ground samples by AOAC
      methods for percentage of DM, CP, ether extract (EE), and Ash. Percentage of fat
      free mass (FFM) was calculated from the percentage of moisture and CP.
      Correlation and stepwise regression procedures were used to identify the most
      reliable independent variables for predicting chemical composition. Independent
      variables included electromagnetic scan data and live animal measures for weight,
      body length, and chest girth circumference. Electromagnetic data included the
      average scan response curve (PH0) and Fourier transformations (P1T, P1R, P2T, and
      P2R). Repeatability of the HA-2 model was extremely high (r = .98). Reliable
      prediction equations were obtained for DM, CP, EE, and FFM (R2 > .66). The
      percentage of ash could not be predicted from the independent variables.
      Electromagnetic scan responses contributed little to the model sum of squares.
      Body weight accounted for the majority of the model sum of squares. Depriving
      lambs of food for 24 h slightly improved the R2 value and significantly decreased
      scan responses (P < .01). Body weight was a better predictor of chemical
      composition over a large weight range than any of the scan responses. Further
      investigation of the HA-2 is needed to determine whether it is effective in
      determining differences in live body composition between animals of equal weight.

PMID- 8856442
TI  - Mathematical modeling of digestion and nutrient absorption in pigs.
AB  - A simple simulation model of digestion and absorption in pigs was developed. The
      structure of the model is a set of four anatomical compartments for DM: stomach,
      two portions of small intestine, and the large intestine. In each of these
      anatomical compartments, subcompartments correspond to the major biochemical
      components of feed and their products of degradation. The major degradation and
      absorption events are considered as well as the effect of microbial activity in
      the large intestine. The total number of compartments is 44. The numerical
      integration with a time step of 1 min allows prediction of kinetic features of
      digestion phenomena such as absorption patterns and transit flows. First
      validation of the model shows that the global dynamic behavior of the model is
      realistic and promising. However, some additional factors must be considered for
      improved accuracy, in particular the susceptibility of the feed components to
      enzymatic degradation. The outputs of such a model could be used as inputs for
      metabolic or growth models running with time steps smaller than the 24-h basis
      often used in nutrition.

PMID- 8856443
TI  - Effect of dietary copper and fat on nutrient utilization, digestive enzyme
      activities, and tissue mineral levels in weanling pigs.
AB  - Two 15-d nutrient balance trials were conducted using a total of 32 weanling
      barrows (averaging 6.8 kg, 26 d). The effect of the addition of 15 or 250 ppm Cu
      (as CuSO4.5H2O) to diets containing 0 or 5% added animal fat on nutrient
      utilization, digestive enzyme activities, and tissue mineral levels in weanling
      pigs was investigated. In each trial, four groups of four littermate barrows were
      randomly assigned to one of four treatments in a 2 x 2 factorial arrangement. The
      addition of 250 ppm Cu improved apparent fat digestibility and apparent nitrogen
      retention (P < .02). The addition of 5% fat increased apparent fat digestibility
      (P < .01). There were no Cu x fat interactions (P > .10) for any of the
      digestibility indices measured. The addition of 250 ppm of Cu stimulated small
      intestinal lipase (P < .01) and phospholipase A (P < .05) activities but had no
      effect (P > .10) on pancreatic lipase or phospholipase activities and no effect
      on trypsin, chymotrypsin, or amylase activities in the small intestine or the
      pancreas. The addition of 250 ppm Cu to the diet increased Cu (P < .001) in
      plasma, liver, and kidney and decreased Fe in plasma (P < .05) and liver (P <
      .02). The addition of 5% fat increased Fe in kidney (P < .05) and heart (P <
      .08). Copper x fat interactions were observed for spleen Ca (P < .01), Mg (P <
      .08), Na (P < .05), and K (P < .08) and spleen weight (P < .05). In additional in
      vitro assays, increased Cu concentrations tended to consistently stimulate
      purified porcine pancreatic lipase activity (linear, P < .01) but not purified
      porcine pancreatic phospholipase A activity (P > .10). The results from this
      study indicate that 250 ppm Cu stimulated intestinal lipase and phospholipase A
      activities, leading to an improvement of dietary fat digestibility in weanling
      pigs.

PMID- 8856444
TI  - Effect of feeding raw soybeans on polyamine metabolism in chicks and the
      therapeutic effect of exogenous putrescine.
AB  - The inclusion of isolated soy protein in milk replacer diets for calves and
      neonatal pigs inhibits development of intestinal mucosal cells. Simultaneous
      administration of putrescine partially overcomes this effect. We therefore
      conducted experiments to determine the potential for dietary putrescine to
      overcome the toxicity of raw soybeans in chicks. In the first experiment, week
      old chicks were fed either an isolated soy protein-based control diet or an
      isoenergetic and isonitrogenous diet containing 52% raw, ground soybeans for 14
      d. The feeding of raw soybeans depressed (P < .001) growth and feed consumption,
      caused enlargement (P < .001) of the duodenum and pancreas, depressed (P < .001)
      activities of polyamine synthetic enzymes in the duodenum, and reduced (P < .01)
      duodenal tissue concentrations of putrescine. In the second experiment, the diet
      containing raw soybeans was fed with and without .2, .3, and .4% supplemental
      putrescine. The feeding of supplemental putrescine largely overcame the
      inhibition of growth due to the feeding of raw soybeans and increased intestinal
      putrescine concentrations. Putrescine supplementation had no effect, however, on
      pancreatic and intestinal enlargement in birds fed raw soybeans and tended to
      depress the activity of polyamine synthetic enzymes. The beneficial effects of
      putrescine supplementation were confirmed in the third experiment when up to 1.0%
      supplemental putrescine was fed. We conclude that the toxicity of raw soybeans to
      chicks can be overcome by feeding putrescine. These effects are likely due to
      improved nutrient uptake by overcoming the adverse effects of lectins in the
      intestinal tract and are not likely due to alleviation of the pancreatic
      enlargement caused by protease inhibitors.

PMID- 8856446
TI  - A cellular and endocrine characterization of the original and induced corpus
      luteum after administration of a gonadotropin-releasing hormone agonist or human
      chorionic gonadotropin on day five of the estrous cycle.
AB  - To determine whether injection of hCG or GnRH-agonist on d 5 after estrus (d 0)
      has a differential functional effect on an induced and the original corpus luteum
      (CL), two experiments were conducted. In Exp. 1, nonlactating Holstein cows were
      injected on d 5 with saline (n = 4; T1), a GnRH-agonist (Buserelin, 8 micrograms
      i.m.; n = 4; T2), or hCG (1,000 i.u., i.v., and 2,000 i.u., i.m.; n = 4; T3).
      Induced CL were removed on d 13 and weights were different (GnRH-agonist < hCG).
      In vitro production of progesterone by CL tissue (microgram/g; microgram/CL) was
      affected by treatment (GnRH-agonist < hCG) and dose of LH (ng.mL) in culture
      media. Experiment 2 was a replicate of Exp. 1, except that the original CL was
      removed on d 17 for in vitro culture. Day-17 CL weights and in vitro production
      of progesterone by original CL were not affected by treatment. The daily rate of
      increase of plasma progesterone from d 6 to d 13 differed: saline < GnRH-agonist
      < hCG (P < .01). From d 14 to 17, the rate of plasma progesterone decrease was
      not different between treatments. Electron micrographic study of the original and
      induced CL indicates that LH-like exposure delays involution of steroidogenic
      luteal cells. In summary, the higher levels of progesterone from d 6 to d 13 of
      the estrous cycle following an injection of hCG vs GnRH-agonist on d 5 is due to
      a greater response of hCG-induced CL.

PMID- 8856445
TI  - Comparison of circulating concentrations of reproductive hormones in boars of
      lines selected for size of testes or number of ovulations and embryonal survival
      to concentrations in respective control lines.
AB  - The objectives of this study were to determine whether circulating concentrations
      of genadotropins and gonadal hormones of boars were altered as a result of
      selection of pigs for size of testes or for embryonal survival and(or) number of
      ovulations. Included in Exp. 1 and 2 were boars with the greatest estimated
      paired weight of testes (TS) and boars from a control (C) line. Concentrations of
      FSH were similar (P > .10) in boars from the TS and C lines. In Exp. 3, 4, and 5,
      circulating concentrations of FSH and 17 beta-estradiol (E2) were evaluated in
      neonates, during pubertal development, and in mature boars of lines selected for
      an index of number of ovulations and embryonal survival (I), and data were
      compared to those for boars from a respective C line. Concentrations of E2 were
      not different in boars from the I line and those from the C line during the early
      neonatal period but were greater (P < .05) in boars of the C line than in those
      from the I line during pubertal development. Concentrations of FSH were greater
      (P < .05) in mature boars from the I line than in those from the C line. In
      summary, selection for size of testes did not influence circulating
      concentrations of FSH in mature boars. The secretory pattern of E2 in boars
      before puberty changed as a result of selection for embryonal survival and number
      of ovulations in females of the I line, and the different patterns of circulating
      E2 early in life may result in enhanced circulating concentrations of FSH in
      adult boars of the I line compared with boars of the C line.

PMID- 8856447
TI  - Luteal function in unilaterally hysterectomized ewes treated with gonadotropin
      releasing hormone.
AB  - An experiment was conducted to examine effects of GnRH administered to ewes
      during metestrus on subsequent luteal and uterine functional interrelationships.
      Treatments consisted of GnRH (0 or 100 micrograms/d) and uterine status (intact
      or unilaterally hysterectomized [UHYST]). On d 12 of an estrous cycle, all ewes
      were unilaterally ovariectomized and one-half of these ewes were subjected to
      contralateral UHYST. Corpora lutea in the remaining ovary were enucleated. One
      half of the intact and UHYST ewes were injected i.v. with 2 mL of GnRH on d 2 and
      3 after subsequent estrus, and the remaining ewes were injected similarly with 2
      mL of saline. Jugular blood samples were collected at 15-min intervals after GnRH
      or saline injection and analyzed for serum LH. Caudal vena caval and(or) jugular
      blood were collected daily from d 5 to 10 and on d 12 and 14 of the cycle and
      analyzed for progesterone, oxytocin, and prostaglandin F2 alpha (PGF2 alpha).
      Injection of ewes with GnRH increased serum concentrations of LH within 60 min
      compared with those of saline-treated ewes (P = .01). Treatment with GnRH did not
      alter concentrations of oxytocin in intact or UHYST ewes (P > .10) but on d 12
      and 14 mean jugular concentrations of oxytocin were greater (P = .01) in intact
      than in UHYST ewes. Vena cava plasma concentrations of PGF2 alpha did not differ
      (P > .10) among treatments. Treatment with GnRH did not affect (P > .10) serum
      concentrations of progesterone, but concentrations of this steroid over the
      sampling period tended to be greater (P = .09) in UHYST ewes than in intact ewes.
      In conclusion, treatment of intact and UHYST ewes with GnRH failed to alter
      systemic concentrations of oxytocin, PGF2 alpha, and progesterone; however, the
      concentrations of oxytocin were affected by unilateral hysterectomy.

PMID- 8856448
TI  - Age and breed differences in thyroid hormones, insulin-like growth factor (IGF)-I
      and IGF binding proteins in female horses.
AB  - A survey with horses was conducted to determine whether plasma concentrations of
      triiodothyronine (T3), thyroxine (T4), insulin-like growth factor (IGF)-I and IGF
      binding proteins (IGFBP) change as horses grow, mature sexually, and age. Jugular
      blood was sampled from Standardbred fillies and mares at ages 0, 1, 7, and 14 d,
      at 1, 2, 4, 5, 6, and 9 mo, and at 5 to 8 and 16 to 22 yr (n = 5 to 18). In a
      second survey, we measured the same variables in eight breeds of horses with
      markedly different adult body sizes, from Miniatures to Friesians. Plasma T3, T4,
      and IGF-I were determined by radioimmunoassays validated for horses, and IGFBP
      were estimated from radioligand assay following separation of the IGFBP by SDS
      PAGE electrophoresis. Plasma T3 decreased (P < .01) nearly continuously from 7.9
      ng/mL on the day of birth to .9 ng/mL at 6 mo, and then changed little from .7
      ng/mL at 9 mo to .5 ng/mL in mares 16 to 22 yr old. Similarly, T4 declined (P <
      .01) from 233 ng/mL on the day of birth to 49 ng/mL at 14 d and varied from 35 to
      9 ng/mL among all of the older age groups. Plasma concentrations of IGF-I
      increased (P < .01) from 285 ng/mL on the day of birth to 572 ng/mL at 14 d,
      remained relatively constant until 9 mo of age (530 ng/mL), and then declined (P
      < .01) to low levels (295 ng/mL) in the oldest mares. We detected six IGFBP. The
      two smallest IGFBP (26 and 39 kDa) were highest during the first 14 d after birth
      and lowest (P < .01) in aged mares. The four larger IGFBP were lowest at birth
      and increased to the highest values during the most rapid growth period, but
      these changes were not significant (P > .20). In agreement with data for other
      species, our data suggest that IGF-I and IGFBP modulate growth in horses.
      Although there were impressive interbreed differences in circulating
      concentrations of T3, T4, IGF-I, and IGFBP, these were not related to differences
      in adult body size.

PMID- 8856449
TI  - Relationship of fertility to patterns of ovarian follicular development and
      associated hormonal profiles in dairy cows and heifers. Cooperative Regional
      Research Project.
AB  - Ovarian follicular development, hormonal patterns, and fertility were compared
      for growing and persistent follicles in 98 lactating dairy cows and in 89
      heifers. Pregnancy rates were greater in animals that ovulated the first-wave
      dominant follicle while it was growing (GF) vs persistent (PF; for cows 54.2 vs
      14.0%, P < .001; for heifers 62.0 vs 35.9%, P < .05). Follicles were larger in
      cows than in heifers (P < .05). Preovulatory growth rate (mm/d) for PF in cows
      was parallel to that of GF in both groups; in heifers, PF grew more slowly. At
      estrus, PF were larger than GF in cows and overall (P < .001), but not in
      heifers. Estradiol in plasma was greater (P < .05 in animals with PF than in
      those with GF before estrus (for 6 d in heifers, 8 d in cows). During d -6
      through -2, progesterone in plasma tended to be lower (P = .12) in cows with PF
      than in heifers with PF. Pulse frequency of LH in plasma increased on d 7 in
      animals with GF and more frequent LH pulses continued through d 13 and 14 in
      animals with PF. After AI, progesterone in plasma did not differ between GF and
      PF, in either cows or heifers. However, among cows with GF, progesterone was
      greater (P < .01) by d 6 to 7 after estrus in pregnant than in nonpregnant cows.
      In summary, fertility was lower in animals that ovulated a persistent rather than
      a growing follicle, especially in lactating cows. Lower fertility in animals with
      PF was associated with prolonged increases in concentrations of LH and estradiol
      in plasma before estrus and ovulation.

PMID- 8856450
TI  - Immunogenicity of cholecystokinin octapeptide-conjugated antigens in pigs.
AB  - An improved antigen is required to raise antiserum titers against cholecystokinin
      higher than those observed in previous studies to demonstrate the effect of
      immunoneutralization of cholecystokinin on feed intake in swine. Four immunogenic
      carrier proteins were compared. Unsulfated cholecystokinin octapeptide (CCK8ns)
      was conjugated to each of human serum globulin (HSG), BSA, Keyhole limpet
      hemocyanin (KLH), and Tuberculin purified protein derivative (PPD). Forty
      crossbred swine (four from each of 10 litters, 78 d of age, 22 kg BW) were
      randomly assigned to the four conjugated antigens by litter. The primary and
      three booster doses of antigen were injected at 14-d intervals. A blood sample
      was drawn before the primary dose on d 1 to assess basal nonspecific binding of
      antigen. Additional blood samples were drawn on d 22, 29, 36, 43, 50, 57, 71, and
      92 to follow the time course of antiserum titer expression (d 1 = day of primary
      dose). Titer is the serum dilution that binds 50% of 1 fmol of radiolabeled
      antigen. Titers, compared by ANOVA of log titer values, were different between
      antigens (P < .01) and between litters (P < .01). Mean titer (n = 40; 10 pigs,
      four samples/pig) during the period after the immune response (d 50, 57, 71, and
      92) was 55, 115, 176, and 535 for BSA, HSG, KLH, and PPD, respectively. It is
      concluded that the carrier protein component has an important effect on
      immunogenicity of conjugated CCK antigens in pigs; BSA was inferior and KLH and
      PPD were superior to HSG.

PMID- 8856451
TI  - Early-vegetative tall fescue hay vs alfalfa hay as a supplement for cattle
      consuming low-quality roughages.
AB  - Two studies were conducted to evaluate high-quality tall fescue hay as a
      supplement to beef cattle fed low-quality roughages. In Exp. 1, 15 ruminally
      cannulated Hereford x Angus steers (average weight 390 kg) were blocked by weight
      and assigned randomly to one of three treatments: 1) tall fescue straw, no
      supplement; 2) tall fescue straw plus tall fescue hay supplement; 3) tall fescue
      straw plus alfalfa hay supplement. The 28-d digestion study consisted of 14 d of
      adaption, 6 d of intake data, and 6 d of collection of feces, respectively, with
      a 1-d ruminal sampling (d 27) and ruminal evacuations (d 28). In Exp. 2, 90
      gestating Hereford x Angus cows were stratified by age and body condition and,
      within stratum, assigned randomly to three replications of the same treatments as
      described for Exp. 1. In both studies, a basal diet of tall fescue straw was fed
      with ad libitum access, alfalfa hay was fed at .4% BW, and tall fescue hay was
      fed at a level isonitrogenous with the alfalfa hay (.61% BW). In Exp. 1, DMI was
      at least 13% greater (P < .01) for supplemented steers than for nonsupplemented
      steers and was 12% greater (P < .10) for steers receiving supplemental tall
      fescue hay than for alfalfa hay-supplemented steers. Digestibility of DM was
      greater for supplemented steers than for nonsupplemented steers (P < .05) and,
      between supplement treatments, greater for tall fescue hay-supplemented steers
      than for alfalfa hay-supplemented steers (P < .10). Ruminal ammonia values peaked
      at 3 h after feeding and were higher for steers fed supplement treatments than
      for those fed the control treatment from just before feeding through 6 h after
      feeding (P < .10). In Exp. 2, supplemented cows gained more BW than
      nonsupplemented cows (P < .01), and the tall fescue hay-supplemented cows gained
      more BW (P < .10) than cows supplemented with alfalfa hay. Likewise, supplemented
      cows lost less condition (P < .01) than their nonsupplemented counterparts during
      the 84-d supplementation period, and cows receiving tall fescue hay supplement
      tended (P = .23) to lose less condition than cows receiving alfalfa hay
      supplement. No differences in calf growth were noted among treatment groups (P <
      .10). In conclusion, supplementation of high-quality tall fescue hay to cows fed
      low-quality forage diets seems to result in performance that is similar to or
      better than that of cows receiving alfalfa hay supplements when fed on an
      isonitrogenous basis.

PMID- 8856452
TI  - Barley varieties for finishing steers: I. Feedlot performance, in vivo diet
      digestion, and carcass characteristics.
AB  - Eighty Angus x Hereford steers (average initial weight 287 kg) were used in a 168
      d finishing study to evaluate the effects of barley variety on feedlot
      performance, diet digestion, and carcass characteristics. The four treatments
      compared in this completely randomized design (four pens/ treatment) were high
      concentrate diets based on 1) corn, 2) Gunhilde barley (GUN), 3) Harrington
      barley (HAR), or 4) Medallion barley (MED). Steers consuming corn gained 10%
      faster (P < .01) than steers fed HAR, and HAR resulted in 8% faster (P < .01)
      gains than GUN or MED. Dry matter intake was greater (P < .01) for steers fed
      corn than for steers fed GUN, HAR, or MED, and HAR-fed steers consumed more than
      MED-fed steers. Efficiency (kilograms of gain/100 kg of feed) was higher (P <
      .05) for steers fed GUN, HAR, and MED than for corn-fed steers. Estimated NEm and
      NEg of barley varieties ranged from 2.32 to 2.51 Mcal of NEm/kg and 1.61 and 1.77
      Mcal of NEg/kg. Carcass weight was greater (P < .01) for steers fed corn rather
      than HAR and greater (P < .01) for HAR-fed steers than for those fed GUN or MED.
      Quality grade was higher (P < .05) for HAR-fed steers than for steers fed corn,
      GUN, or MED. Steers fed corn had the highest (P < .01) digestible starch intake,
      followed by steers fed HAR, GUN, and, finally, MED, the same approximate ranking
      as for ADG. A diet based on Harrington barley resulted in greater DMI, ADG, and
      carcass quality grade compared with diets based on Gunhilde or Medallion barleys.

PMID- 8856453
TI  - Barley varieties for finishing steers: II. Ruminal characteristics and rate,
      site, and extent of digestion.
AB  - Four ruminally and abomasally cannulated steers were used to evaluate the effects
      of barely variety on rate, site, and extent of digestion of high-concentrate
      diets. The treatments compared were 1) corn, 2) Gunhilde barley (GUN), Harrington
      barley (HAR), and 4) Medallion barley (MED). Diets were balanced to be isocaloric
      and isonitrogenous. Ruminal OM digestion was greater (P = .04) in steers fed corn
      than in those fed GUN, HAR, and MED (61.9 vs average 53.7%). No differences (P >
      .10) were seen in ruminal starch digestion (average 92.8%) or in starch flow to
      the abomasum (average 199 g/d) between diets. Total tract digestion of starch was
      greater (P = .09) in steers fed barley than in those fed corn (average 98.6 vs
      95.7%). Total and nonammonia N presented to the abomasum were greater (P < .05)
      for steers fed HAR and GUN than for those fed MED and corn. Microbial N flow was
      lowest (P = .01) in corn-fed steers, highest in steers fed GUN and HAR, and
      intermediate in steers fed MED. Microbial efficiency was 59% greater (P = .03) in
      steers fed barley than in steers consuming corn. Ruminal acetate: propionate was
      lower (P = .002) in steers fed corn and HAR than in those fed GUN and MED.
      Compared to GUN, HAR, and MED barleys, corn had a lower (P < .03) rate (-.11 vs
      average -.47) and extent (15 h; 70.3 vs average 98.1%) of in situ starch
      disappearance. Differences in digestive characteristics found between barley
      varieties may contribute to differences in animal performance.

PMID- 8856454
TI  - Effects of organic acid and monensin treatment on in vitro mixed ruminal
      microorganism fermentation of cracked corn.
AB  - The objective of this study was to determine the effects of organic acids and
      monensin on the in vitro fermentation of cracked corn by mixed ruminal
      microorganisms. Ruminal fluid was collected from a steer fed 36.3 kg of wheat
      silage and 4.5 kg of concentrate supplement once daily. Mixed ruminal
      microorganisms were incubated in anaerobic media that contained 20% (vol/vol)
      ruminal fluid and .4 g of cracked corn. Incubations were carried out in batch
      culture for 24 h at 39 degrees C. Organic acids (L-aspartate, fumarate, and DL
      malate) were added to serum bottles (n = 4) to achieve final concentrations of 0,
      4, 8, or 12 mM. Monensin, dissolved in ethanol, was included in serum bottles at
      a final concentration of 0 or 5 ppm of culture fluid. The addition of 8 and 12 mM
      organic acids to cracked corn fermentations increased final pH (P < .05), tended
      to increase total gas production and CO2 concentration, and decreased the
      acetate:propionate ratio (P < .05). Organic acids tended to decrease methane
      concentrations and hydrogen concentration was not altered. DL-Malate addition at
      all levels reduced (P < .05) lactate accumulation. Additive effects of monensin
      and organic acids were observed in some fermentations. In conclusion, organic
      acid addition to in vitro mixed ruminal microorganism fermentations yielded
      beneficial results independent of monensin treatment by decreasing the acetate:
      propionate ratio and increasing final pH.

PMID- 8856455
TI  - Using aversion learning techniques to assess the mental state, suffering, and
      welfare of farm animals.
AB  - The extent that handling farm animals causes them to suffer is a central concern
      when assessing their welfare. "Suffering" is a mental state, resulting from
      different emotions, such as fear, pain, or boredom, which have different causes
      and effects on the animal's behavior and physiology. What is common is that they
      are aversive; animals will seek to avoid such experiences. The degree of
      aversiveness can be measured using behavioral techniques, which are based on an
      animal's ability to learn the predictive relationships between events. Compared
      with physiological stress responses, aversion learning techniques are more easily
      interpreted in terms of animal suffering and are more able to discriminate
      between handling treatments. They can sometimes be used to predict physiological
      responses to handling. The outcome of experiments in aversion learning can be
      affected by factors influencing the learning ability and memory of animals, and
      researchers need be aware of potential confounding in experimental design. Such
      techniques have been used to compare sheep handling practices, examine which
      components of transport are aversive for pigs and poultry, and examine the
      relationship between animals and handlers.

PMID- 8856456
TI  - Assessing sensory capacity of animals using operant technology.
AB  - Operant technology is often employed in farm management (e.g., waterers in which
      an animal pushes a valve with its nose or snout [response] to receive water
      [reinforcement]). An animal learns when successive approximations to the desired
      response are reinforced, thereby establishing the operant behavior (shaping).
      Animals are challenged by schedules of reinforcement that increase level of
      operant response. The method has been used to obtain quantitative measures of
      preference for prepared feeds, flavors, and harvest methods and feed processing.
      Basic information on what an animal sees in terms of color, patterns, and
      illumination are cited. Innovative research on animals' ability to smell and to
      hear are reviewed. Studies on regulation of environmental conditions by the
      animals themselves through operant methods will contribute to needed knowledge
      about animal welfare. Several examples of these studies are included in this
      review. Results of numerous studies indicate that operant technology can be a
      powerful tool to assess the sensory capacity of animals.

PMID- 8856457
TI  - Acquired aversions as the basis for varied diets of ruminants foraging on
      rangelands.
AB  - Ruminants eat an array of plant species that vary in nutrients and toxins. This
      selection makes intuitive sense, but no theories adequately explain this
      diversity. Some maintain it reduces the likelihood of overingesting toxins,
      whereas others contend it meets nutritional needs. Nevertheless, herbivores seek
      variety even when toxins are not a concern and nutritional needs are met. I offer
      another explanation for this behavior, one which encompasses the avoidance of
      toxins and the acquisition of nutrients. A key concept in this theory is
      aversion, the decrease in preference for food just eaten as a result of sensory
      input (a food's taste, odor, texture, i.e., its flavor) and postingestive effects
      (effects of nutrients and toxins on chemo-, osmo-, and mechano-receptors) unique
      to each food. Aversions are pronounced when foods contain toxins or high levels
      of rapidly digestible nutrients; they also occur when foods are deficient in
      specific nutrients. Aversions occur even when animals eat nutritionally adequate
      foods because satiety (satisfied to the full) and surfeit (filled to nauseating
      excess) represent points along a continuum, and there is a fine line between
      satiety and aversion. Thus, eating any food is likely to cause a mild aversion,
      and eating a food too frequently or in excess is likely to cause a strong
      aversion. Aversions are involuntary and are not the result of conscious decisions
      by an animal. Aversions yield benefits (e.g., obtain a balanced diet, reduce
      ingestion of toxic foods, optimize foraging and rumination times, sample foods,
      maintain a diverse microflora in the rumen) that are often mistaken as the cause
      of varied diets. In this article, I discuss the subtle ways in which aversions
      diminish preference and cause animals to eat a variety of foods.

PMID- 8856458
TI  - Characterization of growth parameters needed as inputs for pig growth models.
AB  - Swine growth models have the potential to evaluate alternative management
      decisions and optimize production systems. However, the lack of economical, yet
      accurate methods to obtain the growth parameters required to characterize pig
      genotypes, and which are required by growth models, limits their widespread
      implementation. The four primary parameters required are 1) daily whole-body
      protein accretion potential, 2) partitioning of energy, intake over maintenance
      between protein and lipid accretion, 3) maintenance requirements for energy, and
      4) daily feed intake. Estimation of daily protein accretion rates requires that
      serial estimates of composition and growth be fitted to flexible nonlinear
      functions. Serial dissection and chemical analysis are too expensive to be
      routinely conducted on an adequate number of pigs for precise daily protein
      accretion rates at different live weights. Three alternate methods include 1)
      serial slaughter and double sampling; 2) use of serial live measurements to
      estimate composition, i.e., serial ultrasonic measurements; and 3) use of
      generalized functions that estimate daily protein accretion as a function of mean
      daily fat-free lean gain over a specified weight interval. The energy
      partitioning between lipid and protein accretion can be expressed as two
      interchangeable measurements, either as the slope of protein accretion or the
      change in the lipid: protein gain ratio as a function of energy intake at each
      live weight. Both methods require serial estimates of composition and scale
      feeding of pigs to specified energy intake levels. Maintenance requirements for
      energy are better expressed as a function of protein mass than body weight.
      However, differences in body protein mass do not fully explain difference in
      maintenance requirements between various pig genotypes. Daily feed intakes at
      each live weight can be estimated by accurately collecting feed intake data at
      least three live weight ranges and fitting the data to nonlinear functions. An
      alternative method to estimate daily feed intake is to develop daily lipid and
      protein accretion curves. On the basis of their energetic costs of lipid and
      protein deposition and assumed maintenance requirements, daily energy intakes can
      be estimated. Genetic selection changes the underlying growth parameters. The
      selection criteria and testing environment direct the relative genetic change for
      each growth parameter. The different sexes may also be affected differently by
      selection. For this reason, each closed uniformly selected population must be
      evaluated for each parameter for each sex.

PMID- 8856459
TI  - Persistence of single echo beat inducibility after selective ablation of the slow
      pathway in patients with atrioventricular nodal reentrant tachycardia:
      relationship to the functional properties of the atrioventricular node and
      clinical implications.
AB  - INTRODUCTION: Residual slow pathway conduction with or without reentrant echo
      beats has been reported in 25% to 30% of patients undergoing ablation for AV
      nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: Fifty-eight consecutive
      patients (aged 45 +/- 12 years) with slow-fast AVNRT underwent radiofrequency
      catheter ablation of the slow AV nodal pathway (SP). Residual slow-fast echo beat
      was documented in 21 (36%) of 58 patients (group A). The pre- and postablation AH
      intervals triggering the echo beats were similar (346 +/- 8 msec vs 352 +/- 6
      msec, P = NS), as were the pre- and postablation echo zones (55 +/- 6 msec vs 52
      +/- 5 msec, P = NS) and functional refractory period of the SP. A consistent
      prolongation of the AV nodal effective refractory period (AVN-ERP; from 265 +/-
      28 msec to 340 +/- 50 msec, P < 0.001) and the Wenckebach cycle length (WBCL;
      from 298 +/- 41 msec to 438 +/- 43 msec, P < 0.001) was observed in all patients
      with abolition of SP conduction (group B). In group A patients, the prolongation
      of WBCL was less (285 +/- 33 msec preablation, and 334 +/- 41 msec postablation,
      P < 0.001). Additional pulses abolished the residual echo in 16 of 21 patients,
      and further prolongation of the AVN-ERP and WBCL comparable to those found in
      patients without a residual echo beat was observed. During 19 +/- 8 months follow
      up, no patient had clinical recurrence of AVNRT. CONCLUSION: Residual single echo
      beat after SP ablation for AVNRT reflects the persistence of some portion of the
      SP with unchanged functional conduction properties whose prognostic significance
      is uncertain. A consistent increase of WBCL can be a reliable marker of complete
      abolition of slow pathway conduction and termination of AVNRT.

PMID- 8856460
TI  - Serial defibrillation lead impedance in patients with epicardial and
      nonthoracotomy lead systems.
AB  - INTRODUCTION: The stability of implantable cardiac defibrillation lead impedance
      subsequent to implantation has not been reported and may have important clinical
      implications. The objective was to characterize the incidence and degree of
      impedance changes occurring after implantation of defibrillation lead systems.
      METHODS AND RESULTS: The study cohort consisted of patients who received
      epicardial or nonthoracotomy lead systems. Defibrillation impedance was recorded
      at implantation, prior to hospital discharge (predischarge), and during follow
      up. For each individual the magnitude of the impedance change relative to
      implantation was characterized. Among patients with an epicardial system, a
      significant decrease in impedance was observed at predischarge (mean 9.3 omega).
      The magnitude of the decrease was large in 39% and moderate in 31% of
      individuals. Subsequently, a gradual rise in mean impedance was apparent. At 18
      21 months postimplantation, impedance was significantly increased relative to
      implantation (mean 6.8 omega). At this time, the magnitude of the increase was
      large in 46% and moderate in 23% of patients. Among patients with a
      nonthoracotomy lead system including a subcutaneous patch, a significant decrease
      in mean impedance was observed at predischarge (mean 3.5 omega). The magnitude of
      the decrease was large in 8% and moderate in 50% of individuals. Subsequently, a
      gradual rise in impedance was apparent. At 5-6 months, it was significantly
      increased relative to implantation (mean 2.3 omega). The magnitude of the
      increase was large in 10% and moderate in 33% of patients. Among the group of
      patients whose nonthoracotomy lead system did not include a subcutaneous patch,
      there was no significant change in mean impedance at predischarge relative to
      implantation. In subsequent intervals, a gradual rise was apparent. At 5-6
      months, impedance was significantly increased relative to implantation (mean 4.3
      omega). The magnitude of the increase was large in 16% and moderate in 47% of
      individuals. CONCLUSION: Significant changes in defibrillation lead impedance
      occur after implantation of epicardial and nonthoracotomy defibrillation lead
      systems. These data may serve as a standard for identifying the anticipated
      maximum change in lead impedance and thus may be useful as a tool for recognizing
      problems with defibrillation lead integrity.

PMID- 8856461
TI  - Recurrence of conduction following radiofrequency catheter ablation procedures:
      relationship to ablation target and electrode temperature. The Atakr Multicenter
      Investigators Group.
AB  - INTRODUCTION: More than 1 in 10 patients may develop recurrence of conduction
      after undergoing a successful radiofrequency catheter ablation procedure. The
      physiologic basis for recurrence following successful ablation procedures remains
      uncertain. The purpose of this study was to evaluate the role of electrode
      temperature as a predictor of recurrence following radiofrequency catheter
      ablation procedures. METHODS AND RESULTS: The subjects of this study were 538
      patients who underwent a successful attempt at radiofrequency catheter ablation
      of AV nodal reentrant tachycardia, an accessory pathway, and/or the AV junction.
      Patients were followed for a mean of 215 +/- 138 days. Conduction recurred in 35
      (6.5%) of the 538 patients. Recurrence of conduction occurred in 25 (9.3%) of 270
      patients undergoing ablation of an accessory pathway, 7 (3.5%) of 201 patients
      undergoing ablation of AV nodal reentrant tachycardia, and in 3 (4.5%) of 67
      patients undergoing ablation of the AV junction. The electrode temperature
      achieved at successful sites associated with recurrence was not different from
      the temperature achieved at successful sites without recurrence (61.1 +/- 8.9 vs
      61.6 +/- 9.1; P = 0.8). The likelihood of developing a recurrence was higher
      following ablation of accessory pathways than following ablation of AV nodal
      reentrant tachycardia or the AV junction (P = 0.03). Patients experiencing a
      recurrence following ablation of an accessory pathway had longer procedure
      durations (P = 0.0001). Ablation of left free-wall pathways was associated with a
      lower incidence of recurrence as compared with all other locations (P = 0.008).
      CONCLUSION: The results of this study suggest that electrode temperature at the
      successful ablation site cannot be used to identify patients at highest risk of
      recurrence.

PMID- 8856462
TI  - Amiodarone instilled into the canine pericardial sac migrates transmurally to
      produce electrophysiologic effects and suppress atrial fibrillation.
AB  - INTRODUCTION: We investigated whether amiodarone delivered into the pericardial
      sac exerted an effect on atrial and ventricular refractoriness, impulse
      generation, and conduction and on induced atrial fibrillation. METHODS AND
      RESULTS: All animals were anesthetized with alpha-chloralose. After a sternotomy,
      the pericardium was opened and cradled to produce a "container" of approximately
      75 mL. Part I experimental animals received amiodarone, 0.5, 1.0, or 5.0 mg/mL,
      dissolved in 3 mL polysorbate 80 and 5% dextrose in water (D5W) instilled into
      their pericardial sac for 3-hour intervals. Part II experimental animals received
      either 1.0 or 5.0 mg/mL of amiodarone. Control dogs received a pericardial
      solution of 3 mL polysorbate 80 in D5W. Pre- and postinstillation
      electrophysiologic studies were performed. In part I, the increase in sinus cycle
      length, 1:1 AV conduction, and effective refractory period (ERP) of atrium, right
      ventricular (RV) and left ventricular epicardium, and RV endocardium were
      significantly greater in animals receiving amiodarone compared with controls.
      Amiodarone concentrations in the tissue samples were highest in the superficial
      sites of the atria, sinoatrial node, and ventricular epicardial samples and
      lowest in the interventricular septum. Only trace concentrations of amiodarone
      and no desethylamiodarone were found in the blood samples. In part II, atrial ERP
      significantly increased in the animals receiving amiodarone, and the number of
      episodes of sustained atrial fibrillation that could be induced decreased.
      CONCLUSIONS: Amiodarone instilled into the pericardial sac migrates transmurally
      to produce significant electrophysiologic effects at superficial sites and
      appears to suppress electrically induced atrial fibrillation.

PMID- 8856463
TI  - Strength-interval curves for cardiac tissue predicted using the bidomain model.
AB  - INTRODUCTION: Strength-interval curves are predicted for unipolar anodal and
      cathodal stimulation of cardiac muscle. METHODS AND RESULTS: Cardiac tissue is
      represented by the bidomain model, and the active properties of the membrane are
      described by the Beeler-Reuter model. Two successive stimuli (S1 and S2) are
      delivered through a single extracellular electrode. The S2 threshold is
      determined as a function of the S1-S2 interval, for anodal and cathodal S2
      stimuli with 2-, 5-, 10-, and 20-msec durations. Each of the resulting cathodal
      and anodal strength-interval curves is divided into two parts: one section
      corresponding to make stimulation (long intervals) and the other section
      corresponding to break stimulation (short intervals). Generally, the cathodal
      strength-interval curves are decreasing functions of interval, except for an
      anomalous section of the 20-msec duration cathodal curve in the interval range
      from 310 to 318 msec. At short intervals, the anodal strength-interval curve
      contains a deep dip, which is more prominent for longer S2 durations. The
      cathodal threshold is less than the anodal threshold for all intervals except
      those corresponding to the end of the refractory period. CONCLUSION: The bidomain
      model predicts complex anodal and cathodal strength-interval curves, with the
      anodal curve containing a dip (supernormal stimulation). These results resemble
      the experimental observations of Dekker.

PMID- 8856464
TI  - Long reflections on the QT interval: the sixth annual Gordon K. Moe Lecture.
AB  - This review of accumulated knowledge about the long QT syndromes begins with an
      iteration of the original papers and then proceeds to a broader historic
      reflection that includes my personal work as well as many studies by others. Next
      come reflections upon the current status of knowledge on the subject, combined
      with comments about remaining challenges and questions grouped as follows: (1)
      morphologic abnormalities of the cardiac conduction system and their
      pathophysiologic significance in the long QT syndromes; (2) cardioneuropathy in
      the pathogenesis of long QT syndromes; (3) variability of QT prolongation,
      including consideration of peripheral and central dysautonomic conditions with
      certain diagnostic and therapeutic implications; (4) some caveats about the
      popular use of left cervical sympathectomy to treat symptomatic individuals with
      long QT syndrome, emphasizing hazards for future electrical instability of the
      heart; (5) consideration of genetic influences in the long QT syndromes, a field
      holding great promise as well as fraught with many puzzling dilemmas; and (6)
      apoptosis and the pathogenesis of the long QT syndromes, based upon personal
      observations previously made with electron microscopic studies of the sinus node
      and now including new immunohistochemical evidence expanding the relevance of
      this novel view-point. These intentionally provocative presentations are made to
      stimulate physicians and other scientists to consider these several different
      perspectives in planning future studies aimed at better understanding of one of
      the most challenging medical entities facing cardiology today.

PMID- 8856465
TI  - Syncope and the autonomic nervous system.
AB  - The autonomic nervous system plays a central role in the maintenance of
      hemodynamic stability. Dysfunction of this complex regulatory system can lead to
      the development of loss of consciousness. This article summarizes our current
      understanding of the role of the autonomic nervous system in maintaining a stable
      blood pressure and heart rate under normal and abnormal physiologic conditions.
      The role of baroreceptors, mechanoreceptors, chemoreceptors, vascular reactivity,
      and the interaction of these sensor systems with the central nervous system as a
      whole are reviewed. Current concepts related to the mechanisms of unexplained
      syncope and the "state-of-the-art" diagnostic and treatment options are also
      discussed.

PMID- 8856466
TI  - Will QT dispersion play a role in clinical decision-making?
AB  - (1) Dispersion of QT intervals is the difference between the longest and the
      shortest QT interval in the ECG. Owing to the relative ease of measurement and
      the perceived need for new markers of arrhythmogenicity, the method has attracted
      the interest of clinical investigators but has not reached the level of practical
      utility. (2) It is postulated that to pass the test of practical utility, the
      method must meet the following criteria: (a) standardization; (b) establishment
      of normal values; (c) established sensitivity and/or specificity for diagnosis
      and/or prognosis; and (d) uniqueness of relevant information. (3) Analysis of the
      data from the literature suggests that standardization of the method and the
      range of normal values have not been established, and that the method lacks
      specificity for separating healthy persons from patients with heart disease. (4)
      Large values, such as average QT dispersion > 65 msec, have been found
      predominantly in patients with serious, life-threatening ventricular
      tachyarrhythmias, and the largest values, i.e., > 110 msec in patients with
      congenital long QT syndrome. (5) The prognostic value of QT dispersion has been
      disputed, and the uniqueness of the relevant information has not been tested. (6)
      It is concluded that the acceptance of QT dispersion as a useful test in practice
      faces manifold and serious obstacles. It remains to be established whether these
      obstacles are insurmountable.

PMID- 8856467
TI  - His electrogram analysis: is it anterograde or retrograde?

PMID- 8856468
TI  - Therapy of Wolff-Parkinson-White syndrome.

PMID- 8856469
TI  - T wave memory.

PMID- 8856470
TI  - Transvenous defibrillators without EP testing.

PMID- 8856471
TI  - Hemostatic changes after dietary coenzyme Q10 supplementation in swine.
AB  - Improved cardiovascular morbidity and mortality have been observed in several
      clinical studies of dietary supplementation with coenzyme Q10 (CoQ10). We
      elucidated the effect of CoQ10 on certain hemostatic parameters that may
      influence the progression of heart disease. Twelve Yorkshire swine were
      randomized to receive diet supplementation with either CoQ10 or placebo for 20
      days. Blood samples were obtained at baseline and at the end of the feeding
      period. At the end of the protocol, there were no significant differences in
      hemostatic parameters in the placebo group. A significant increase in total serum
      CoQ10 level (from 0.39 +/- 0.06 to 0.96 +/- 0.04 microgram/ml, p < 0.001) was
      noted after the feeding period in the CoQ10-supplemented group. We observed
      significant inhibition of ADP-induced platelet aggregation (-9.9%) and a decrease
      in plasma fibronectin (-20.2%), thromboxane B2 (TXB2, -20.6%), prostacyclin (
      23.2%), and endothelin-1 (ET-1, -17.9%) level. There were no changes in the
      plasma concentrations of the natural antithrombotics [antithrombin-III (AT-III),
      protein S, and protein C] after CoQ10 supplementation. CoQ10 supplementation in a
      dose of 200 mg daily is associated with mild antiaggregatory changes in the
      hemostatic profile. Clinical beneficial effects of CoQ10 may be related in part
      to a diminished incidence of thrombotic complications.

PMID- 8856472
TI  - Electrophysiological and inotropic characterization of a novel class III
      antiarrhythmic agent, GLG-V-13, in the mammalian heart.
AB  - GLG-V-13, a novel 3,7-diheterabicyclo(3.3.1)nonane, was examined both in vivo and
      in vitro to characterize its electrophysiological, hemodynamic, and inotropic
      properties. In anesthetized guinea pigs, GLG-V-13 [0.5-500 micrograms/kg
      intravenously (i.v.), n = 6] lengthened the epicardial monophasic action
      potential (MAP) duration, the atrioventricular (AV) conduction time and the RR
      interval in a dose-dependent manner. At the highest dose, these variables were
      increased by 30, 13, and 23%, respectively. No significant effects were noted on
      QRS duration or blood pressure (BP). In rabbit atrial and papillary muscle
      preparations, GLG-V-13 (0.32-3.2 mg/L) did not exert a negative inotropic action
      and in isolated rabbit cardiomyocytes the agent blocked the rapidly activating
      delayed rectifier K+ current (IKr, EC50 = 48 micrograms/L). In 10 intact
      anesthetized mongrel dogs, the left ventricular (LV) endocardial MAP was measured
      during atrial pacing before and after administration of GLG-V-13 (3 and 6 mg/kg
      i.v.). As compared with the drug-free state, the agent induced a significant
      prolongation of the MAP at all pacing frequencies (2.0-4.5 Hz). In 15
      anesthetized dogs studied 1-4 days after two-stage ligation of the left anterior
      descending coronary artery (LAD), the antiarrhythmic/proarrhythmic potential of
      GLG-V-13 was compared with that of lidocaine. ECG, His bundle, LV (IZepi), and
      composite and normal zone composite electrograms were recorded. Programmed
      electrical stimulation (PES) and burst pacing (4.0-7.0 Hz) were delivered to the
      right ventricular outflow tract. In the drug-free state, sustained monomorphic
      ventricular tachycardia (SMVT) was inducible in 6 dogs (6 of 15). After
      lidocaine, SMVT was induced in 7 other dogs (13 of 15). GLG-V-13 prevented
      induction of SMVT in 5 of 6 dogs; a proarrhythmic action was noted in 1 dog only.
      GLG-V-13 slowed the heart rate (HR), increased the AH and the HV intervals,
      prolonged the paced (2.5 Hz) QT interval, and increased the ventricular effective
      refractory period (VERP). These effects were associated with 2:1 block of late
      potentials in the IZepi electrograms, a phenomenon also observed during rapid
      atrial pacing (2.5-3.5 Hz), suggestive of a marked prolongation of refractoriness
      in the ischemically damaged myocardium. In light of the recent Cardiac Arrhythmia
      Suppression Trial (CAST) study, the antiarrhythmic efficacy, together with the
      low proarrhythmic potential and lack of cardiodepressant properties of GLG-V-13,
      may merit further investigation of this novel class III antiarrhythmic agent.

PMID- 8856473
TI  - Characterization of signaling pathways of P2Y and P2U purinoceptors in bovine
      pulmonary artery endothelial cells.
AB  - The actions of ATP on the endothelium are mediated by P2 purinoceptors. We have
      shown that P2Y and P2U purinoceptors coexist in bovine pulmonary artery
      endothelial cells (CPAE), where they induce phosphoinositide (PI) turnover and
      Ca2+ mobilization. The relative order of potency (based on the threshold
      concentration) of nucleotide analogues (1-100 microM) in stimulating the
      accumulation of inositol phosphate (IP) was 2-methylthio-ATP (2MeSATP) = 2
      methylthio-ADP (2MeSADP) > or = 2ClATP > UTP = ATP = ADP. alpha, beta-methylene
      ATP, beta, gamma-methylene ATP, UDP, adenosine-5'-tetraphospho-5'-adenosine, and
      adenosine-5'-pentaphospho-5'-adenosine had no effect at concentrations as high as
      100 microM. At maximal concentrations, the IP responses to 2MeSATP and UTP were
      additive, whereas those to ATP and either 2MeSATP or UTP were not. Moreover, the
      maximal response to 2MeSADP was additive to that to UTP but not to that of
      2MeSATP. Pretreatment with pertussis toxin slightly inhibited 2MeSATP- and UTP
      stimulated IP generation by 15%. Under Ca(2+)-free conditions, UTP-induced IP
      formation was inhibited more markedly than that induced by 2MeSATP. Short-term
      treatment of the cells with phorbol 12-myristate-13-acetate (PMA) resulted in a
      dose-dependent inhibition of 2MeSATP-induced IP formation greater and more
      sensitive than that induced by UTP; similar results were obtained for the
      sensitivity of inhibition by suramin and reactive blue. Stimulation of the cells
      with either 2MeSATP or UTP induced a rapid increase in intracellular Ca2+ level,
      followed by a slow decrease to basal levels, followed by Ca2+ level oscillation.
      In the absence of extracellular Ca2+, [Ca2+]i responses were quantitatively less
      and did not show the slow phase and oscillation. Together these results suggest
      that both P2Y and P2U purinoceptors are expressed in bovine pulmonary artery
      endothelial cells and are coupled to phospholipase C (PLC) activation and Ca2+
      mobilization through pertussis toxininsensitive G proteins.

PMID- 8856474
TI  - Tranilast restores cytokine-induced nitric oxide production against platelet
      derived growth factor in vascular smooth muscle cells.
AB  - Tranilast has been reported to reduce restenosis rate after angioplasty, but its
      mechanism is still unclear. We investigated the effect of tranilast against
      platelet-derived growth factor (PDGF) in PDGF's proliferative effect and PDGF's
      inhibitory effect on cytokine-induced nitric oxide (NO) production in vascular
      smooth muscle cells (VSMC). NO production was measured by Griess reaction. NO
      synthase (NOS) protein was evaluated by Western blot with monoclonal anti-rat
      inducible NOS antibody. A combination of interleukin-1 beta (IL-1 beta 1 ng/ml),
      tumor necrosis factor-alpha (TNF-alpha 2,000 U/ml), and lipopolysaccharide (100
      ng/ml) significantly increased NO production and NOS protein, and tranilast
      significantly enhanced both in a dose-dependent manner. PDGF (100 ng/ml)
      significantly reduced both cytokine-induced NO production and NOS protein
      induction, but tranilast completely abolished these inhibitory effects. In the
      presence of cytokines, serum-stimulated cell proliferation was significantly
      inhibited by cytokine-induced NO, whereas PDGF-stimulated proliferation was not.
      On the other hand, tranilast not only inhibited the proliferative effect of PDGF
      directly, but also restored cytokine-induced NO production and its
      antiproliferative effect in the presence of PDGF.

PMID- 8856475
TI  - Inhibition of vasoconstriction by phosphodiesterase III inhibitor milrinone in
      human conduit arteries used as coronary bypass grafts.
AB  - We wished to determine the effect of phosphodiesterase III (PDE III) inhibitor
      milrinone on human arteries used as coronary bypass grafts. Human internal
      mammary artery segments (IMA, n = 109) taken from 25 patients were studied.
      Concentration-relaxation curves for milrinone were established in IMA
      precontracted with four vasoconstrictors [K+, endothelin-1 (ET-1), U46619, and
      phenylephrine (PE)]. In IMA rings incubated with therapeutic plasma
      concentrations of milrinone (7 and 70 microM) for 10 min, concentration
      contraction curves for the four vasoconstrictors were constructed. Milrinone
      caused a complete relaxation in U46619, ET-1, PE (100%), or K+ (97.7%)
      precontracted IMA. The EC50 value was higher against K+ (-5.31 +/- 0.27 log M)
      than PE (-6.20 +/- 0.25 log M, p = 0.036) or endothelin-1 (-6.41 +/- 0.28 log M,
      p = 0.018). Pretreatment with milrinone decreased the contraction induced by ET-1
      from 186.0 +/- 23.3 to 66.9 +/- 9.6% (p = 0.002) and that induced by PE from
      140.6 +/- 27.6 to 54.1 +/- 7.0% (p = 0.03) and shifted the EC50 7.6-fold higher
      (p = 0.003). Treatment of milrinone reduced the K+ and U46619 contraction (p <
      0.05) at lower concentrations (between 10 and 80 mM for K+ and -8.5 and -7.5 log
      M for U46619) and shifted the concentration-contraction curves rightward (2.56
      fold higher for K+, p < 0.0001; 3.18-fold higher for U46619, p = 0.007).
      Denudation of endothelium did not affect the milrinone-induced relaxation. These
      results demonstrate that milrinone is a potent vasodilator of human conduit
      arteries used as coronary bypass grafts and may have a slight selectivity with
      greater potency to receptor stimulants than to the depolarizing agent K+. The
      results may prove a particular indication for milrinone for use in patients
      receiving arterial grafts for coronary bypass.

PMID- 8856476
TI  - Intracellular levels of cyclic AMP and cyclic GMP differentially modify platelet
      aggregate size in human platelets activated with epinephrine or ADP.
AB  - We investigated the effects on human platelet aggregation of several agents that
      increase either intracellular cyclic AMP or cyclic GMP, using a platelet
      aggregometer that allows quantification of the size and number of platelet
      aggregates. During the initial phase of aggregation induced by epinephrine and
      ADP, small aggregates consisting of < 100 cells predominated; large aggregates
      formed later. Prostaglandin I2 (PGI2), which increases intracellular cyclic AMP,
      suppressed the formation of small as well as large aggregates induced by
      epinephrine, with ID50 values of 10.7 +/- 2.8 and 3.8 +/- 0.5 nM, respectively.
      ADP-induced formation of small and large aggregates was also inhibited by PGI2,
      with similar ID50 values. Dibutyryl cyclic AMP (db cyclic AMP), a cell-permeant
      form of cyclic AMP, also inhibited small and large aggregate formation induced by
      epinephrine or ADP, with ID50 values of 420-560 microM for small aggregates and
      139-166 microM for large aggregates, respectively. On the other hand,
      nitroprusside, which increases intracellular cyclic GMP, inhibited only the
      formation of large aggregates, with an ID50 value of 454 +/- 191 nM for
      epinephrine-induced activation and of 2.1 +/- 0.6 microM for ADP-induced
      activation. Nitroprusside at 1 mM did not affect the formation of small
      aggregates induced by epinephrine, whereas that of large aggregates was
      completely blocked at 10 microM. 8-Bromo cyclic GMP (8-br cyclic GMP) also
      inhibited only the formation of large aggregates, with ID50 values of 140-170
      microM, but not that of small aggregates induced by epinephrine and ADP.
      Milrinone, which increases the intracellular level of both cyclic AMP and cyclic
      GMP, suppressed the formation of small and large aggregates induced by
      epinephrine and ADP. These findings suggest that cyclic AMP and cyclic GMP
      differentially modify the size of aggregates formed during epinephrine or ADP
      activation.

PMID- 8856477
TI  - Effects of angiotensin II receptor blockade during exercise: comparison of
      losartan and saralasin.
AB  - Previous studies indicate that angiotensin II (ANG II) plays a minor role in the
      hemodynamic responses during dynamic exercise. However, nonspecific effects
      associated with methods used to block its production [e.g., angiotensin
      converting enzyme (ACE) inhibitors] or receptors (e.g., saralasin) may have
      contributed to these findings. Losartan is a nonpeptide ANG II receptor
      antagonist that is devoid of such nonspecific effects. We hypothesized that the
      contribution of ANG II to the cardiovascular response to dynamic exercise is
      characterized more precisely with losartan than with saralasin. On separate days,
      6 miniswine performed treadmill running at 80% of their maximal heart rate (HR)
      reserve (HRR) in the presence of vehicle (0.9% saline), saralasin (10 or 20
      micrograms/kg/min intraleft arterially, i.a.), or losartan (15 or 20 mg/kg i.a.).
      Cardiac output (CO), HR, and myocardial contractility were similar among all
      exercise conditions. As compared with the vehicle, losartan decreased mean
      arterial pressure (MAP) and systemic vascular resistance (SVR) during exercise,
      whereas no differences occurred between the vehicle and saralasin conditions.
      Both receptor antagonists increased blood flow and/or decreased vascular
      resistance during exercise in the myocardium, stomach, small intestine, and
      colon. As compared with that during treadmill running with vehicle infusion,
      renal blood flow (RBF) was increased by losartan and decreased by saralasin. We
      conclude that the contribution of ANG II to the cardiovascular response to
      dynamic exercise is demonstrated more clearly with losartan than with saralasin.

PMID- 8856478
TI  - Impaired coronary sensitivity to diltiazem in experimental heart failure:
      involvement of the cyclooxygenase but not the nitric oxide-synthase pathway.
AB  - Because controversies surround the increased negative inotropic effects of
      calcium antagonists in heart failure, other mechanisms may explain their lack of
      efficacy in this condition. We hypothesized that altered coronary sensitivity
      through endothelial dysfunctions may be involved. Our goal was to evaluate the
      effects of heart failure on coronary and cardiac sensitivity to the calcium
      antagonist diltiazem. Left ventricular developed pressure (LVP) and coronary flow
      (CF) were assessed in isovolumetrically beating, perfused, failing hearts from
      cardiomyopathic hamsters (UM-X7.1) and hearts from normal hamsters. Diltiazem
      concentration-response curves for both coronary dilation and its negative
      inotropic effects were charted under control conditions and in the presence of
      the specific nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl
      ester (L-NAME, 30 microM), and the cyclooxygenase inhibitor, indomethacin (10
      microM). Diltiazem concentration-response curves for its negative inotropic
      action were similar in normal and failing hearts (IC50 1.2 and 2.3 microM,
      respectively). In contrast, the coronary dilator effects of diltiazem were
      impaired in failing hearts (EC50 for diltiazem-induced coronary dilation
      increased from 90 nM in normal hearts to 1.1 microM in failing hearts, p < 0.01).
      The involvement of endothelial dysfunctions in the observed coronary
      "desensitization" to diltiazem in heart failure was evaluated through the NO
      synthase and cyclooxygenase pathways. Diltiazem concentration-response curves
      from failing hearts were not modified in the presence of L-NAME, whereas
      indomethacin normalized the coronary response to diltiazem in heart failure.
      These findings suggest that coronary "desensitization" to diltiazem occurs
      through parallel production and/or release of a vasoconstricting factor or
      factors originating from the cyclooxygenase pathway. Heart failure was not
      associated with increased cardiac sensitivity to diltiazem but rather with
      altered coronary sensitivity. These findings suggest that coronary
      desensitization may play a role in the lack of efficacy of diltiazem in heart
      failure and provide a better understanding of factors modulating the effects of
      calcium antagonists in heart failure.

PMID- 8856479
TI  - Tumor necrosis factor-alpha, platelet-activating factor, and hydrogen peroxide
      activate protein kinase C subtypes alpha and epsilon in human saphenous vein
      endothelial cells.
AB  - Protein kinase C (PKC), the major receptor for tumor-promoting phorbol esters,
      consists of a family of at least 12 distinct lipid-regulated enzymes. We examined
      the expression and regulation of PKC isoforms in human saphenous vein endothelial
      cells (HSVEC). Western blot analysis with PKC isoform-specific antibodies
      indicated that PKC alpha, PKC epsilon and PKC zeta were expressed in these cells.
      Translocation and down-regulation of PKC alpha and epsilon but not zeta were
      detected by short-term and long-term treatment with TPA (12-O
      tetradecanoylphorbol 13-acetate), respectively. Tumor necrosis factor-alpha (TNF
      alpha 1,600 U/ml) and platelet activating factor (PAF 50 nM) increased the
      membrane content of PKC alpha and epsilon but not zeta. H2O2 (10 mM) induced the
      translocation of PKC alpha from the cytosol to the membrane and increased PKC
      epsilon content in both cytosol and membrane. However, 12-(S)-HETE (12
      hydroxyeicosatetraenoic acid) (100 nM), a lipoxygenase metabolite of arachidonic
      acid, did not affect the two isoforms. These results suggest that the molecular
      action of TNF-alpha, PAF, and H2O2 in HSVEC might occur through PKC alpha and
      epsilon activation.

PMID- 8856480
TI  - Regional hyperinsulinemia induces vasodilation but does not modulate adrenergic
      responsiveness in humans.
AB  - The relation between insulin resistance/ hyperinsulinemia and cardiovascular
      disease may be related to one of the cardiovascular effects of insulin. In acute
      experiments in humans, systemic euglycemic hyperinsulinemia induced vasodilation
      in skeletal muscle. Furthermore, the sympathetic nervous system is activated,
      although this does not lead to increase in blood pressure (BP). We hypothesized
      that insulin could induce vasodilation either by reduction of alpha- or by
      augmentation of beta-adrenergic responsiveness. The effect of insulin infusion
      into the brachial artery (regional forearm hyperinsulinemia; venous insulin
      concentration approximately 500 pM) on forearm blood flow (FBF: plethysmography)
      was studied. Responses to the alpha-adrenoceptor-mediated vasoconstrictor
      norepinephrine (NE: once with and once without the beta-adrenoceptor antagonist
      propranolol, 2 x n = 12; 9 participated in both), and to the beta-adrenoceptor
      mediated vasodilator isoproterenol (n = 12) were measured before and during local
      hyperinsulinemia. Time/control studies (n = 6) were performed. Insulin alone
      induced vasodilation, as indicated by an increase in FBF-ratio (infused/ control
      arm) from 1.2 +/- 0.1 to 1.6 +/- 0.2, p = 0.009. Increasing dosages of NE (1.25
      to 240 ng.dl-1.ml-1) induced vasoconstriction that was more pronounced during
      concomitant propranolol infusion (p < 0.001), indicating a dose-dependent
      vasodilatory component in the effect of NE. Isoproterenol (ISO 0.03 to 10 ng.dl
      1.ml-1), a pure beta-adrenoceptor agonist, induced vasodilation. The percentage
      changes of FBF-ratio during NE+propranolol were similar and not significantly
      different before and during hyperinsulinemia. The same was true of the response
      to NE alone and the response to ISO. Neither was the intrinsic beta-agonist
      component of NE influenced by insulin. Repeated NE infusion showed no time- or
      vehicle effect. We conclude that regional hyperinsulinemia in the physiological
      range induces local vasodilation in the skeletal muscle vascular bed, but this
      vasodilation is not mediated through modulation of alpha- or beta-adrenergic
      responsiveness.

PMID- 8856481
TI  - Clinical and hormonal effects of the new angiotensin II receptor antagonist
      LRB081.
AB  - The renin-angiotensin system is a major contributor to the pathophysiology of
      cardiovascular diseases such as congestive heart failure and hypertension.
      Antagonizing angiotensin (Ang) II at the receptor site may produce fewer side
      effects than inhibition of the promiscuous converting enzyme. The present study
      was designed to assess in healthy human subjects the effect of LRB081, a new
      orally active AT1-receptor antagonist, on the pressor action of exogenous Ang II.
      At the same time, plasma hormones and drug levels were monitored. At 1-week
      intervals and in a double-blind randomized fashion, 8 male volunteers received
      three doses of LRB081 (10, 40, and 80 mg) and placebo. Blood pressure (BP) was
      measured at a finger by photoplethysmograph. The peak BP response to intravenous
      injection of a standard dose of Ang II was determined before and for < or = 24 h
      after administration of an oral dose of LRB081 or placebo. After drug
      administration, the blood BP response to Ang II was expressed in percent of the
      response before drug administration. At the same time, plasma renin activity
      (PRA), Ang II, aldosterone, catecholamine (radioassays), and drug levels (by high
      performance liquid chromatography) were monitored. After LRB081 administration, a
      dose dependent inhibition of the BP response to Ang II was observed. Maximal
      inhibition of the systolic BP response was 54 +/- 3 (mean +/- SEM), 63 +/- 2, and
      93 +/- 1% with 10, 40, and 80 mg LRB081, respectively. The time to peak was 3 h
      for 6 subjects and 4 and 6 h for 2 others. Preliminary plasma half-life (t1/2)
      was calculated at 2 h. With the highest dose, the inhibition remained significant
      for 24 h (31 +/- 5%, p < 0.05). Maximal BP-blocking effect and maximal plasma
      drug level coincided, suggesting that the unmetabolized LRB081 is responsible for
      the antagonistic effect. PRA and Ang II increased dose dependently after LRB081
      intake. Aldosterone, epinephrine, and norepinephrine concentrations remained
      unchanged. No clinically significant adverse reaction was observed during the
      study. LRB081 is a well-tolerated, orally active, potent, and long-acting Ang II
      receptor antagonist. Unlike in the case of losartan, no active metabolite of
      LRB081 has been shown to be responsible for the main effects.

PMID- 8856482
TI  - Effects of losartan on renal function in patients with essential hypertension.
AB  - We examined the renal hemodynamic modifications induced by a selective
      angiotensin II (AII) AT1 receptor antagonist, losartan, in 10 patients with
      essential hypertension. In this single-blind study, renal hemodynamic parameters
      were determined twice (patients were their own controls) first after a 15-day
      single-blind placebo run-in period and again after a 1-month losartan period. The
      dosage of losartan was 50 mg/day. Glomerular filtration rate (GFR, inulin
      clearance), renal plasma flow [RPF; para-aminohippurate (PAH) clearance],
      microalbuminuria, sodium excretion, proximal sodium tubular reabsorption (lithium
      clearance), and acid uric metabolism were measured. After 1-month losartan
      treatment, systolic and diastolic BP (SBP, DBP) decreased significantly
      throughout the 210-min recording whereas heart rate (HR) was unchanged. GFR (100
      +/- 19 vs. 96 +/- 17 ml/min/1.73 m2) and RPF (471 +/- 118 vs. 468 +/- 108 ml/
      min/1.73 m2) were not altered by losartan. Rather than occurrence of any
      modification in filtration fraction (FF), a significant decrease in
      microalbuminuria was evident (57 +/- 77 vs. 40 +/- 59 mg/24 h, p < 0.05). Urinary
      sodium excretion was not modified, but an almost significant (p = 0.07) decrease
      in proximal sodium reabsorption was observed (72.9 +/- 7.7 vs. 68.1 +/- 6.4% of
      filtered sodium). The increase in renal uric clearance accounted for the
      significant decrease in serum uric acid (195 +/- 49 vs. 183 +/- 43 microM; p <
      0.05). After 1-month losartan treatment, renal function was well preserved; the
      decrease in uric acid may be of clinical interest when adjuvent diuretic therapy
      is required.

PMID- 8856483
TI  - Effects of adenine nucleotide analogues on myocardial dysfunction during
      reperfusion after ischemia in dogs.
AB  - We examined effects of adenine nucleotide on ischemic myocardial stunning in
      dogs. Pentobarbitalanesthetized open-chest dogs were subjected to 20-min ligation
      of the left anterior descending coronary artery (LAD), followed by reperfusion
      for 30 min. Either saline, 5 mM 8-bromo-5'-AMP (tributyryl-AMP), or 30 mM N6, 2',
      3'-tributyryl-5'-AMP (tributyryl-AMP), 5 mM 5-amino-4-imidazole carboxamide
      riboside (AICAr) as a positive reference, was infused at 0.1 ml/kg/min in the
      left femoral vein throughout the experiment. The myocardial contractile function
      was measured by ultrasonometry. The tissue levels of high-energy phosphates in
      the reperfused heart were determined. Myocardial contractile function assessed by
      % segment shortening (%SS) in the saline-infused group decreased during ischemia
      and returned toward the preischemic level during reperfusion but incompletely. A
      significant improvement in the %SS during reperfusion was observed in the 8-bromo
      AMP- and AICAr-infused groups but not in the tributyryl-AMP-infused group. The
      magnitude of the protective effect of the drugs on myocardial contractility
      during reperfusion was 8-bromo-AMP > AICAr > tributyryl-AMP = saline. Only in the
      8-bromo-AMP-infused group were the levels of ATP, ADP, and total adenine
      nucleotides in the reperfused heart significantly higher than those in the saline
      infused group. The present result indicates that 8-bromo-AMP improves the ability
      of the heart to recover from ischemia and reperfusion associated with a
      significant restoration of ATP.

PMID- 8856484
TI  - Effects of mibefradil on large and small coronary arteries in conscious dogs:
      role of vascular endothelium.
AB  - The systemic and coronary hemodynamic effects of mibefradil, a
      "nondihydropyridine" calcium antagonist acting on both L- and T-type calcium
      channels, were investigated in chronically instrumented conscious dogs before and
      after local endothelium removal of the circumflex coronary artery by angioplasty.
      After intravenous infusion, mibefradil (0.2 mg kg-1 min-1) decreased mean
      arterial blood pressure (MAP; -15 +/- 1%), increased heart rate (HR; 58 +/- 9%),
      and coronary blood flow (CBF; 103 +/- 14%) (all p < 0.05). Before endothelium
      removal, mibefradil increased the diameter of the left circumflex epicardial
      coronary artery (LCX) by 7.8 +/- 1.2% from 3,006 +/- 219 microns, but this
      dilatory effect was significantly reduced by 69% (p < 0.001) and 45% (p < 0.01),
      3 and 21 days after endothelium removal, respectively. Mibefradil also reduced by
      46% (p < 0.01) the potent coronary constrictor effect of ergonovine (300
      micrograms intravenous bolus). These results demonstrate that mibefradil is a
      potent dilator of large and small coronary arteries in conscious dogs and that
      approximately 30% of its dilatory effect on large coronary artery is endothelium
      independent. In addition, mibefradil prevents ergonovine-induced epicardial
      coronary constriction.

PMID- 8856485
TI  - Inhibitory effects of endothelin-3 on antidiuresis and norepinephrine overflow
      induced by stimulation of renal nerves in anesthetized dogs.
AB  - The effects of endothelin-3 (ET-3) on changes in renal hemodynamics, urine
      formation, and norepinephrine (NE) overflow induced by renal nerve stimulation
      (RNS) were examined in anesthetized dogs. RNS at a low frequency (0.5-2.0 Hz)
      produced significant decreases in urine flow (UF), urinary excretion of sodium
      (UNaV), and fractional excretion of sodium (FENa), and increased the NE secretion
      rate (NESR) without affecting systemic or renal hemodynamics. RNS at a high
      frequency (2.5-5.0 Hz), which diminishes renal hemodynamics by causing renal
      vasoconstriction, affected urine formation and NESR more potently than did low
      frequency RNS. When ET-3 (2.0 ng/kg/min) was infused into the renal artery, there
      was a slight and transient increase in renal blood flow (RBF); this response was
      followed by a gradual reduction. ET-3 infusion tended to increase the basal
      levels of UF without affecting UNaV, indicating the excretion of hypotonic urine
      with administration of this peptide. During ET-3 infusion, low-frequency RNS
      induced antidiuretic action was significantly attenuated. Simultaneously,
      increase in NESR elicited by low-frequency RNS was markedly suppressed.
      Qualitatively similar results were observed in the case of high-frequency RNS. In
      addition, high-frequency RNS-induced decreases in the glomerular filtration rate
      (GFR) and the filtration fraction (FF) were suppressed by ET-3 infusion. These
      findings suggest that ET-3 suppresses renal responses to stimulated renal
      noradrenergic neurotransmission by inhibiting the release of NE. These findings,
      together with our previous findings, suggest that ET-3 (and/or ET-1) functions as
      an inhibitory modulator of the renal noradrenergic nervous system through the
      prejunctional ETB-receptor mechanism.

PMID- 8856486
TI  - Inhibitor of angiotensin-converting enzyme modifies myointimal origin in an
      arterial autograft model.
AB  - Pharmacologic modulation by an inhibitor of angiotensin-converting enzyme (IACE:
      cilazapril) of vascular proliferative response to a full-thickness arterial
      injury (autograft) was studied in rats. An arterial autograft 5 mm long was made
      in the right common iliac artery of 50 female Sprague-Dawley rats (weight 250-300
      g) by microsurgical techniques. The animals were divided into two study groups:
      group I (controls), 20 animals that underwent arterial autograft but received no
      other treatment; and group II (cilazapril-treated), 20 rats that underwent
      arterial autograft and received cilazapril (Roche), 10 mg/day orally (p.o.) in an
      excipient of 2% arabic gum, for 4 days before operation. Animals were killed on
      postoperative days 7, 14, 21, 30, and 50, and grafts were studied by light
      microscopy, scanning and transmission electron microscopy, and morphometry. In
      the control group, the hyperplasic response had begun by postoperative day 14 and
      was established by postoperative day 50. In the medial layer, the muscle cells
      changed in phenotype from contractile to secretory cells. The adventitia had a
      highly proliferative appearance. In the cilazapril-treated group, fibrin deposits
      and platelets formed a layer on the internal elastic lamina. This layer appeared
      to evolve toward an intimal hyperplasia that became quantifiable by postoperative
      day 21. The medial layer was clearly thinned and showed intense accumulation of
      lipid microvacuoles, elastic degeneration, and vacuolized cells. Our results
      suggest that the use of an inhibitor of ACE modified the origin of the intimal
      hyperplasia in the arterial autograft model. Enhancement of the thrombogenicity
      of the luminal surface favors myointimal development by thrombus reorganization.

PMID- 8856487
TI  - Hypotensive and reflex bradycardic effects of ketanserin, but not of prazosin,
      enhanced selectively in aging conscious rats.
AB  - To determine whether cardiovascular effects of ketanserin are altered differently
      with aging as compared with those of prazosin, we recorded blood pressure (BP)
      and heart rate (HR) changes produced by treatment with either drug in three age
      groups of conscious Sprague-Dawley rats. BP was decreased more by ketanserin in
      24-month than in 4- or 14-month-old rats, but was decreased equally by prazosin
      in all age groups. Pressor responses to phenylephrine (PE) were consistently
      abolished by both drugs, indicating that the greater hypotensive effects of
      ketanserin in 24-month-old rats were not due simply to alpha 1-adrenergic
      blockade. By contrast, baroreflex sensitivity, determined from reflex HR
      responses to infused angiotensin or sodium nitroprusside (SNP), was altered
      differently in old rats by ketanserin but not by prazosin. Whereas enhancement of
      reflex bradycardia by prazosin occurred at all ages, it was demonstrable only
      with ketanserin in older rats. Moreover, reflex tachycardia was unaffected by
      prazosin but was reversed to bradycardia by ketanserin in older rats. Because
      these differences persisted even after the data had been normalized to compensate
      for differences in baseline pressures, effects on HR reflexes were considered age
      dependent for ketanserin but not for prazosin. Although the underlying mechanisms
      are not clear, the selective enhancement of reflex bradycardia and reversal of
      reflex tachycardia in old rats by ketanserin, but not by prazosin, could explain
      why hypotensive responses to ketanserin increase with age whereas those to
      prazosin do not.

PMID- 8856488
TI  - Central effects of caffeine on renal renin secretion and norepinephrine
      spillover.
AB  - Endogenous adenosine in the brain may inhibit central sympathetic tone and
      thereby restrain renin release, a mechanism that may be particularly important
      when sympathetic activity is enhanced. The purpose of our study was to test the
      hypothesis that the adenosine receptor antagonist caffeine increases renin
      release in part by disabling the central nervous system (CNS) adenosine brake on
      renin release. This hypothesis was tested by conducting three protocols in
      anesthetized rats. In the first protocol, intracerebroventricular (i.c.v.)
      infusions of caffeine (10 micrograms/kg/min) did not alter either bradycardic
      responses to intravenous (i.v.) infusion of N6-cyclopentyladenosine (CPA, A1
      receptor agonist) or depressor responses to i.v. infusions of CGS21680 (A1
      receptor agonist). However, i.c.v. caffeine did block bradycardic responses to
      i.c.v. boluses of CPA and depressor responses to i.c.v. boluses of CGS21680, thus
      demonstrating that i.c.v. caffeine at the dose used blocks CNS but not peripheral
      adenosine receptors. In the second protocol, hydralazine (1 and 10 mg/kg,
      administered intraperitoneally) significantly enhanced both the renal secretion
      of renin and the renal spillover of norepinephrine (NE), thus confirming that
      hydralazine can increase renin release by unloading arterial baroreceptors and
      increasing sympathetic tone to the kidneys. In the third protocol, the effects of
      i.c.v. caffeine (10 micrograms/kg/min) on hydralazine-induced (1 and 10 mg/kg,
      administered intraperitoneally) changes in renal secretion of renin and renal NE
      spillover were investigated. In this protocol, i.c.v. caffeine did not alter
      baseline values for either the renal secretion of renin or NE. In contrast,
      i.c.v. caffeine significantly (p = 0.03) enhanced the increase in renal renin
      secretion induced by 1 and 10 mg/kg hydralazine (for 1 mg/kg hydralazine delta of
      6.4 +/- 46.7 and 142.4 +/- 142.9 renin activity/min/kg body weight in control and
      caffeine-treated animals, respectively; for 10 mg/kg hydralazine, delta 227.8 +/-
      73.9 and 600.8 +/- 168.9 renin activity/min/kg body weight in control and
      caffeine-treated animals, respectively). The enhanced renin-secretion response to
      hydralazine in caffeine-treated rats was accompanied by augmented hydralazine
      induced increase in renal NE spillover (p = 0.035). These data strongly support
      the hypothesis of a CNS adenosine brake on renin release that is disabled by
      caffeine.

PMID- 8856489
TI  - Differential class III antiarrhythmic effects of ambasilide and dofetilide at
      different extracellular potassium and pacing frequencies.
AB  - We studied the effect of two new class II antiarrhythmics, ambasilide and
      dofetilide, on the action potential duration (APD) of guinea pig right
      ventricular papillary muscle at different extracellular potassium concentrations
      ([K+e]) and pacing frequencies. Under normal [K+e], both drugs significantly
      prolonged APD90 (APD at 90% repolarization) at 0.5 Hz. The effect of ambasilide
      was well preserved at rapid pacing rates, independent of [K+e]. The effect of
      dofetilide was markedly reduced with increasing pacing rate, especially in high
      [K+e]. Therefore, ambasilide may be useful in treating tachyarrhythmias in
      normal, as well as in altered [K+e] conditions.

PMID- 8856490
TI  - Electrophysiologic effects of a class I antiarrhythmic agent, cibenzoline, on the
      refractoriness and conduction of the human atrium in vivo.
AB  - We investigated the effects of a class I antiarrhythmic drug, cibenzoline, on
      human atrial muscle in vivo. Electrophysiologic measurements were performed in 44
      patients (mean age 49 +/- 15 years), before and after an intravenous infusion of
      cibenzoline 1.4 mg/kg in 5 min. Extrastimuli at a basic cycle length (BCL) of 500
      ms were delivered from the right atrial appendage. The effective refractory
      period of the right atrium (ERP-A), the conduction time from the high right
      atrium to the coronary sinus, maximum conduction delay (Max. CD), repetitive
      atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction
      delay zone (CDZ) were measured. Patients were divided into two groups according
      to whether repetitive atrial firing (RAF) was induced (group A, n = 18) or not
      (group B, n = 26). Cibenzoline increased ERP-A from 198 +/- 25 to 214 +/- 26 ms
      (p < 0.05) and decreased Max. CD from 55 +/- 23 to 43 +/- 19 ms (p < 0.05). There
      were significant decreases in the RAFZ (10 +/- 17 to 4 +/- 10 ms, p < 0.05), the
      FAAZ (20 +/- 25 to 12 +/- 18, ms p < 0.05), and the CDZ (41 +/- 21 to 32 +/- 19
      ms, p < 0.05). Cibenzoline significantly increased ERP.A (186 +/- 25 to 212 +/-
      26 ms, p < 0.05) in group A, but not in group B. There were significant decreases
      in the RAFZ [25 +/- 19 to 9 +/- 15 ms (p < 0.05) and FAAZ 22 +/- 29 to 11 +/- 21
      ms, (p < 0.05)] in group A, but not in group B. The results suggest that
      cibenzoline can suppress paroxysmal atrial fibrillation by prolongation of ERP-A
      and may also have preferential effects on the substrate of atrial fibrillation
      and RAF.

PMID- 8856491
TI  - Relative efficacy and tolerability of lacidipine and amlodipine in patients with
      mild-to-moderate hypertension: a randomized double-blind study.
AB  - Calcium channel blockers are increasingly used in the treatment of hypertension.
      Newer calcium channel blockers of the dihydropyridine group have longer
      elimination half-lives (t1/2) that permit once-daily dosage and are generally
      better tolerated than their parent compound. In this study, the efficacy and
      safety of lacidipine and amlodipine were compared in 65 patients with mild-to
      moderate hypertension attending the hypertension outpatient clinic of a teaching
      hospital in a randomized double-blind cross-over trial with dose titration.
      Lacidipine and amlodipine both significantly reduced systolic blood pressure
      (SBP: by 19.2 +/- 13.5 and 22.3 +/- 15.3 mm Hg, respectively) and diastolic BP
      (DBP: 13.3 +/- 4.2 and 12.3 +/- 5.3 mm Hg, respectively) 24 h postdose. There
      were no significant differences in their antihypertensive effects. The incidence
      of adverse events (AE) was 3% for lacidipine and 8% for amlodipine. The incidence
      of withdrawal from the study due to side effects was 0% for lacidipine and 3% for
      amlodipine. These results suggest that lacidipine is well-tolerated, and is as
      effective as amlodipine as a once-daily antihypertensive agent.

PMID- 8856492
TI  - Cardiovascular effects of (-)-11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl
      in rats.
AB  - The effects of the stereochemically pure psychoactive cannabinoid (-)-11-OH-delta
      8-tetrahydrocannabinol-dimethylheptyl (HU-210) on blood pressure (BP) and heart
      rate (HR) were determined in rats. In pentobarbital-anesthetized animals, the
      compound produced dose-related, long-lasting hypotension and bradycardia at doses
      between 10 and 1,000 micrograms/kg. BP began to decrease immediately after drug
      administration, and in no case was an initial pressor response observed. Previous
      vagotomy (VX) or pretreatment with 6-hydroxydopamine (6-OHDA) did not affect
      hypotension. Bradycardia was inhibited by VX, but only 60 min after
      administration of HU-210; it was enhanced by 6-OHDA. The cannabinoid blocked
      reflex bradycardia induced by phenylephrine (PE). HU-210 also decreased BP and HR
      in conscious rats. Hypotension lasted 2 h, whereas bradycardia was still present
      8 h after drug administration. HU-210 thus shares with delta 9
      tetrahydrocannabinol (THC) the ability to decrease BP and HR, but is 5-10 times
      more potent than the natural compound. Its lack of an initial pressor effect,
      such as that described for THC, could be related to its specificity for the type
      1 cannabinoid (CB1) receptor. Hypotension and bradycardia after HU-210
      administration are not due to sympathetic withdrawal. Enhanced parasympathetic
      tone is involved in bradycardia only at a late stage of the response.

PMID- 8856493
TI  - Kinin-induced prolongation of action-potential duration in right ventricular
      muscle from rat: involvement of B1 and B2 receptors.
AB  - Previous work has shown that, in rat ventricular muscle, bradykinin (BK) causes a
      dose-dependent increase in action potential duration (APD), an action that may be
      responsible for APD prolongation by captopril (kininase II). To determine which
      kinin receptor might be involved in APD prolongation, we studied the effects of
      B1- and B2-receptor agonists, as well as those of antagonists and mergepta (a
      kininase I inhibitor) added during BK superfusion. Action potentials were
      recorded by using the standard glass microelectrode technique in rat ventricular
      muscle preparations. Action-potential characteristics were compared between
      preparations superfused with peptide/drug-free Tyrode's solution (control group)
      and preparations superfused with peptide/drug-containing solution. APD was
      significantly longer in preparations superfused with BK (10(-8) M) than in the
      control group. The APD prolongation induced by BK, a known B2-receptor agonist,
      was significantly reduced by Hoe 140 (a B2 antagonist) and also by Lys[Leu8]des
      Arg9-BK (a B1 antagonist), an action presumably related to inhibition of B1
      receptor stimulation by the BK metabolite des-Arg9-BK. When mergepta was added in
      the presence of BK, APD prolongation by BK was significantly reduced, an effect
      that could have been related to reduced B1-receptor stimulation after inhibition
      of the endogenous generation of des-Arg9-BK by kininase I. Sar4-[d-Phe8]des-Arg9
      BK, a B1-receptor agonist that is not degraded by kininase II, also prolonged
      APD. We conclude that both B1 and B2 receptors may be involved in APD
      prolongation induced in rat ventricular muscle preparations.

PMID- 8856494
TI  - Functional compartmentalization of the nucleus.
AB  - Recent applications of cell biology and molecular genetics have built an image of
      nuclear organization in which the molecular machines involved in transcription,
      RNA processing and replication assemble morphologically distinct nuclear
      organelles with defined functional properties. These observations indicate a very
      high level of structural organization for the various metabolic activities
      occurring within the nucleus. We discuss the possible existence of novel
      regulatory functions inherent to nuclear architecture itself.

PMID- 8856495
TI  - Constructing the mammalian egg zona pellucida: some new pieces of an old puzzle.

PMID- 8856496
TI  - v-Src induces constitutive macropinocytosis in rat fibroblasts.
AB  - The role of v-Src as regulator of fluid-phase pinocytosis was investigated in Rat
      1 cells expressing a stable (Rat-1/BB16) or a thermosensitive (Rat-1/tsLA29) v
      Src protein. In the second cell line, this protein is inactive when cells are
      cultured at 40 degrees C but recovers its tyrosine kinase activity upon transfer
      to 34 degrees C, resulting into a transformed phenotype. The rate of fluid-phase
      pinocytosis of the tracer horseradish peroxidase was 2-fold higher in v-Src
      transformed fibroblasts (Rat-1/BB16, Rat-1/tsLA29 cultured at 34 degrees C) as
      compared to non-transformed cells (Rat-1, Rat-1/tsLA29 kept at 40 degrees C). In
      contrast, receptor-mediated endocytosis of transferrin was poorly affected,
      suggesting that structures distinct from clathrin-coated pits are involved in
      pinocytosis stimulation. By light and electron microscopy, transformed cells
      frequently contained large peroxidase-labeled pinocytic vesicles located near to
      membrane ruffles, demonstrating that stimulation of pinocytosis corresponds to
      induction of constitutive macropinocytosis. Stimulation of pinocytosis occurred
      more than 8 hours after transfer to the permissive temperature, whereas transfer
      to the non-permissive temperature partially reversed the stimulation within 2
      hours. Protein synthesis inhibition for 6 hours abrogated pinocytosis stimulation
      in transformed cells, indicating that constitutive macropinocytosis induced by v
      Src depends on continuous synthesis of a short-lived regulatory machinery.

PMID- 8856497
TI  - Role of laminin-1 and TGF-beta 3 in acinar differentiation of a human
      submandibular gland cell line (HSG).
AB  - Previous studies show that culturing an immortalized human submandibular gland
      cell line (HSG) on Matrigel, a basement membrane extract, induces
      cytodifferentiation. We have further defined this model system and identified
      factors involved in HSG cell acinar development and cyto-differentiation. Acinar
      development is marked by cell migration into multi-cellular spherical structures,
      cell proliferation and apoptosis of the centrally localized cells. In addition,
      functional differentiation was determined by indirect immunofluorescence and
      immunoblot analysis for cystatin, a salivary gland acinar cell-specific protein
      found to be produced by differentiated HSG cells. Matrigel contains multiple
      extracellular matrix proteins, however, laminin-1 was identified as the major
      matrix component that induced HSG cell acinar development and
      cytodifferentiation. Antibodies against specific components of Matrigel and
      against cell surface adhesion molecules were added to cells in culture to
      identify components important for HSG cell acinar differentiation. Immunostaining
      of HSG cell acini identified TGF-beta 2 and beta 3 as the predominant isoforms
      within the cells. Neutralizing antibodies directed against TGF-beta 3
      significantly decreased (P < or = 0.0002) the size of acini formed. These results
      indicate that multiple components, including laminin-1 and TGF-beta 3, contribute
      to HSG cell acinar development. This model system will be useful to study acinar
      differentiation and salivary gland-specific protein expression in vitro.

PMID- 8856498
TI  - Induction of constitutive melanogenesis in amelanotic mouse melanoma cells by
      transfection of the human melanocortin-1 receptor gene.
AB  - The human melanocortin-1 (MC1) receptor was stably expressed in the amelanotic
      mouse melanoma cell clone B16-G4F which does not express its own (mouse) MC1
      receptor and hence is unresponsive to alpha melanocyte stimulating hormone (alpha
      MSH). From several stable transfectant cell lines expressing the human MC1
      receptor in relatively high numbers, three melanin producing clones (G4F-12, 14,
      and 15) and one amelanotic clone (G4F-7) were further analyzed in competition
      binding experiments and in cAMP and melanin assays. The dissociation constants
      (KD) for [Nle4, D-Phe7]-alpha MSH in all four clones ranged from 0.187 to 0.705
      nmol/l, thus corresponding to the KD observed with the different human melanoma
      cell lines so far studied. Intracellular cAMP content was 3- to 5-fold higher
      than that of control cells, and alpha MSH induced an additional 1.5- to 1.7-fold
      increase. G4F-15 cells secreted melanin into the medium whereas the other clones
      did not secrete melanin. The extent of melanin secretion was similar to that of
      fully alpha MSH-stimulated B16-F1 mouse melanoma cells but the onset of secretion
      was delayed. alpha MSH induced an additional dose-related increase (up to 1.3
      fold) in melanin production which could be suppressed by the addition of specific
      alpha MSH antibodies without altering the constitutive part of melanogenesis.
      Human and mouse agouti proteins, which inhibit basal and alpha MSH-induced
      melanogenesis in B16-F1 cells, both reduced alpha MSH-induced melanin production
      in G4F-15 cells but did not affect the constitutive melanogenesis. These results
      indicate that human MC1 receptor expressed in mouse B16-G4F cells induces
      constitutive activation of the signalling pathway controlling melanogenesis, most
      likely by tightly coupling to Gs alpha, in a similar manner to that reported for
      constitutively active receptor mutants in other systems.

PMID- 8856499
TI  - Actin filament bundles are required for microtubule reorientation during growth
      cone turning to avoid an inhibitory guidance cue.
AB  - The extracellular matrix through which growth cones navigate contains molecules,
      such as chondroitin sulfate proteoglycan, that can inhibit growth cone advance
      and induce branching and turning. Growth cone turning is accompanied by
      rearrangement of the cytoskeleton. To identify changes in the organization of
      actin filaments and microtubules that occur as growth cones turn, we used time
      lapse phase contrast videomicroscopy to observe embryonic chick dorsal root
      ganglion neuronal growth cones at a substratum border between fibronectin and
      chondroitin sulfate proteoglycan, in the presence and absence of cytochalasin B.
      Growth cones were fixed and immunocytochemically labeled to identify actin
      filaments and dynamic and stable microtubules. Our results suggest that
      microtubules are rearranged within growth cones to accomplish turning to avoid
      chondroitin sulfate proteoglycan. Compared to growth cones migrating on
      fibronectin, turning growth cones were more narrow, and they contained dynamic
      microtubules that were closer to the leading edge and were more bundled.
      Cytochalasin B-treated growth cones sidestepped laterally along the border
      instead of turning, and in sidestepping growth cones, microtubules were not
      bundled and aligned. We conclude that actin filament bundles are required for
      microtubule reorientation and growth cone turning to avoid chondroitin sulfate
      proteoglycan.

PMID- 8856500
TI  - Function of spindle microtubules in directing cortical movement and actin
      filament organization in dividing cultured cells.
AB  - The mitotic spindle has long been recognized to play an essential role in
      determining the position of the cleavage furrow during cell division, however
      little is known about the mechanisms involved in this process. One attractive
      hypothesis is that signals from the spindle may function to induce reorganization
      of cortical structures and transport of actin filaments to the equator during
      cytokinesis. While an important idea, few experiments have directly tested this
      model. In the present study, we have used a variety of experimental approaches to
      identify microtubule-dependent effects on key cortical events during normal cell
      cleavage, including cortical flow, reorientation of actin filaments, and
      formation of the contractile apparatus. Single-particle tracking experiments
      showed that the microtubule disrupting drug nocodazole induces an inhibition of
      the movements of cell surface receptors following anaphase onset, while the
      microtubule stabilizing drug taxol causes profound changes in the overall pattern
      of receptor movements. These effects were accompanied by a related set of changes
      in the organization of the actin cytoskeleton. In nocodazole-treated cells, the
      three-dimensional organization of cortical actin filaments appeared less ordered
      than in controls. Measurements with fluorescence-detected linear dichroism
      indicated a decrease in the alignment of filaments along the spindle axis. In
      contrast, actin filaments in taxol-treated cells showed an increased alignment
      along the equator on both the ventral and dorsal cortical surfaces, mirroring the
      redistribution pattern of surface receptors. Together, these experiments show
      that spindle microtubules are involved in directing bipolar flow of surface
      receptors and reorganization of actin filaments during cell division, thus acting
      as a stimulus for positioning cortical cytoskeletal components and organizing the
      contractile apparatus of dividing tissue culture cells.

PMID- 8856501
TI  - Granular cells are required for encapsulation of foreign targets by insect
      haemocytes.
AB  - Haemocytes play an essential role in defending invertebrates against pathogens
      and parasites that enter their haemocoel. A primary defense response is
      encapsulation; a process in which haemocytes attach to the foreign organism and
      kill it. Whether encapsulation requires cooperation between specific
      subpopulations of haemocytes is unknown. Using purified subpopulations of
      haemocytes and an in vitro encapsulation assay, we investigated the process of
      capsule formation in the insect Pseudoplusia includens. Immunocytochemical
      staining revealed that capsule formation involves a three step process.
      Encapsulation began when granular cells attached to the foreign target. This was
      followed by attachment of multiple layers of plasmatocytes. Termination of
      capsule formation occurred when a subpopulation of granular cells formed a
      monolayer around the periphery of the capsule. Neither granular cells nor
      plasmatocytes were capable of forming a capsule independently. However,
      plasmatocytes encapsulated targets if granular cells were present or if targets
      were preincubated in medium conditioned by granular cells. The effect of granular
      cell-conditioned medium could be blocked by the addition of the cell adhesion
      recognition sequence, RGDS, but not by RGES. These results demonstrate
      experimentally that granular cells are required for encapsulation of foreign
      targets by plasmatocytes in vitro, and that the role of granular cells in this
      process involves an RGD-dependent cell adhesion mechanism.

PMID- 8856502
TI  - Determination of spatial patterns of DNA damage and repair in intestinal crypts
      by multi-cell gel electrophoresis.
AB  - We have developed a method to quantitate DNA strand breaks as a measure of DNA
      damage and repair in intact, isolated intestinal crypts. The assay is a modified
      form of the single-cell gel electrophoresis or 'comet' assay. By maintaining the
      spatial relationship between the cells we were able to characterise the repair
      response and the susceptibility to DNA damage of cells as a function of their
      position in the crypt. All cells were equally repair competent over the first 30
      minutes of the repair of UV-C and gamma-radiation induced lesions. DNA damage was
      equally distributed following gamma-radiation but following incubation with the
      topoisomerase II inhibitor etoposide, damage was greater in the lower crypt with
      an unusual component to the comet tall which was tapered, implying an incremental
      change in susceptibility by cell position. This tapered component of the comet
      tail resolved rapidly after removal of etoposide. The pattern of damage produced
      by hydrogen peroxide was dose dependent with lower doses producing more strand
      breaks in the base of the crypt-an effect lost at higher doses. The assay has the
      ability to detect differences between cells in their susceptibility to DNA damage
      and their subsequent repair response which may vary with their proliferative or
      differentiative status.

PMID- 8856503
TI  - Tenascin-X expression in tumor cells and fibroblasts: glucocorticoids as negative
      regulators in fibroblasts.
AB  - Tenascin-X has recently been shown to be a novel member of the tenascin family
      and its distribution is often reciprocal to that of tenascin-C in the developing
      mouse embryo. We have investigated the expression of tenascin-X in fibroblasts
      and carcinoma cells in culture. Tenascin-X protein was secreted in vitro in the
      conditioned media at an apparent molecular mass of approximately 450 kDa. In
      addition fibroblasts contained a major tenascin-X isoform of 220 kDa. On northern
      blots, a single major transcript with a size of approximately 13 kb was detected.
      No overexpression of tenascin-X protein was found in primary fibroblasts of the
      tenascin-C-gene knockout mice. Steroid hormone glucocorticoids, were found to
      downregulate tenascin-X mRNA levels and protein synthesis in fibroblasts but not
      carcinoma cells at physiological concentrations. None of the growth factors or
      cytokines examined affected the expression level of tenascin-X. As in vivo study,
      carcinoma cells were transplanted into nude mice. In contrast to the ubiquitous
      presence of tenascin-X in adult skin, expression of tenascin-X protein during
      tumorigenesis was found to be down-regulated considerably not only in tumor cells
      themselves but also in tumor stroma. These findings provide evidence that the
      expression of tenascin-X can be influenced by stromal-epithelial interactions. We
      have identified glucocorticoids as physiological inhibitors of tenascin-X and
      suggest that glucocorticoids may in part participate in the downregulation of
      tenascin-X in fibroblasts in vivo.

PMID- 8856504
TI  - Identification of two distinctly localized mitochondrial creatine kinase
      isoenzymes in spermatozoa.
AB  - The creatine kinase (CK) isoenzyme system is essential for motility in rooster
      and sea urchin sperm. In the present study, biochemical characterization as well
      as immunofluorescence and confocal laser microscopy with highly specific
      antibodies against various chicken CK isoenzymes revealed that cytosolic brain
      type CK isoenzyme (B-CK) is the only CK isoenzyme in rooster seminal plasma,
      while three isoenzymes, cytosolic B-CK, sarcomeric mitochondrial CK (Mib-CK), and
      a variant of ubiquitous Mi-CK ('Mia-CK variant'), are found in rooster
      spermatozoa. These three isoenzymes are localized in different regions of the
      sperm cell. B-CK and Mib-CK were localized along the entire sperm tail and in the
      mitochondria-rich midpiece, respectively. The 'Mia-CK variant', on the other
      hand, was found predominantly at the head-midpiece boundary, in a non-uniform
      manner in the midpiece itself and, surprisingly, at the distal end of the sperm
      tail as well as at the acrosome. Several lines of evidence show that the 'Mia-CK
      variant' shares some characteristics with purified Mia-CK from chicken brain, but
      also displays distinctive features. This is the first evidence for two different
      Mi-CK isoenzymes occurring in one cell and, additionally, for the co-expression
      of Mib-CK and cytosolic brain-type B-CK in the same cell. The relevance of these
      findings for sperm physiology and energetics is discussed.

PMID- 8856505
TI  - The intracompartmental sorting of myosin alkali light chain isoproteins reflects
      the sequence of developmental expression as determined by double epitope-tagging
      competition.
AB  - In order to compare within the same cell the various degrees of specificity of
      myosin alkali light chain (MLC) isoproteins sorting to sarcomeres, a competition
      assay was established using double epitope tagging. Various combinations of two
      different MLC isoform cDNAs tagged with either a vesicular stomatitis virus VSV-G
      (VSV) or a medium T (mT) protein epitope were co-expressed in cultured
      cardiomyocytes from adult and neonatal rat ventricles. Expressed isoproteins were
      detected by means of anti-VSV and anti-mT antibodies and their sorting patterns
      were analyzed by confocal microscopy. The sorting specificity of MLC isoforms to
      sarcomeric sites was shown to increase in the order MLC3nm, to ML1sa, to MLC1sb,
      to MLC1f and MLC3f following the sequence of developmental expression. Expressed
      fast skeletal muscle isoforms (MLC1f and MLC3f) were always localized at the A
      bands of myofibrils, while nonmuscle type (MLC3nm) was distributed throughout the
      cytoplasm. The slow skeletal muscle type (MLC1sa) showed a weak sarcomeric
      pattern if it was co-expressed with MLC3nm, but it was distributed throughout the
      cytoplasm when expressed in combination with MLC1f, MLC3f or the slow
      skeletal/ventricular muscle isoform (MLC1sb). The MLC1sb was localized at the A
      bands when it was co-expressed with MLC3nm or MLC1sa, while it was also
      distributed to the cytoplasm if co-expressed with MLC1f or MLC3f. Further,
      expression of chimeric cDNAs revealed that the N-terminal lobe of each isoprotein
      is responsible for the isoform-specific sorting pattern.

PMID- 8856506
TI  - Single particle tracking of cell-surface HLA-DR molecules using R-phycoerythrin
      labeled monoclonal antibodies and fluorescence digital imaging.
AB  - The mobility of cell surface MHC molecules and their ability to form dynamic
      associations may be related to the physiological status of the cell and to the
      potential to bind effector T lymphocytes. To investigate these properties, we
      have prepared HLA DR specific monoclonal antibodies coupled in a 1:1 mole ratio
      to the fluorescent phycobiliprotein, R-phycoerythrin (PE). We show that these
      small particles can be sequentially imaged using a cooled slow-scan charge
      coupled device camera and hence can be used for single particle tracking
      experiments. We have applied this technique to investigate the movements of HLA
      DR molecules on fibroblasts transfected with human DR alpha and DR beta genes. PE
      IgG was bound to the transfected fibroblasts and particle tracks were obtained by
      sequential imaging over a period of typically 30 minutes. Analysis of particle
      tracks revealed the presence of directed motion and domain-limited diffusion in
      addition to random diffusion. The contributions of these three types of motion
      showed cell to cell variability. Velocities of directed motion were of the order
      of 2 nm second-1 whilst domain diameters were in the range 200-800 nm. Diffusion
      coefficients for random diffusion were in the range 1 x 10(-13)-5 x 10(-12) cm2
      second-1. The higher mobilities were observed for the lower intensity fluorescent
      spots, which possibly correspond to images of single particles. Much lower
      mobility was observed with a cell where the spot intensities were approximately
      double that of the lower intensity spots. These spots could be images of double
      particles implying the association of at least two HLA DR alpha beta dimers.
      These data are relevant to the study of MHC class II cell surface redistribution
      and antigen presentation in specific immunity.

PMID- 8856507
TI  - The internalization of a short acyl chain analogue of ganglioside GM1 in
      polarized neurons.
AB  - In order to study the endocytosis of membrane lipids during the development of
      neuronal polarity, we examined the internalization of a short acyl chain
      fluorescent derivative of ganglioside GM1, N-(6-(4-nitrobenz-2-oxa-1,3-diazole-7
      yl)-aminohexanoyl)-GM1 (C6-NBD-GM1), in hippocampal neurons cultured at low
      density. C6-NBD-GM1 was internalized by temperature- and energy-dependent
      mechanisms, and after short times of incubation, accumulated in endosomes in the
      axon, cell body and dendrites of neurons maintained for up to 4-5 days in
      culture. C6-NBD-GM1 was subsequently transported in a retrograde direction to a
      pool of recycling endosomes in the cell body, with little transport to lysosomes,
      as indicated by the lack of degradation of C6-NBD-GM1 even after long times, and
      the re-appearance of intact C6-NBD-GM1 at the cell surface after recycling;
      similarly, little degradation of C6-NBD-GM1 was detected in N18TG-2 neuroblastoma
      cells. In hippocampal neurons maintained for longer than 6 days in culture, there
      was little internalization of C6-NBD-GM1 along the length of axons, but the
      amount of endocytosis from dendrites was similar to that observed in younger
      neurons. These results demonstrate that gangliosides turnover rapidly in
      dendritic membranes at all stages of neuronal development, whereas ganglioside
      turnover in axons is much less rapid, at least in mature, polarized neurons.

PMID- 8856508
TI  - The envelope of vaccinia virus reveals an unusual phospholipid in Golgi complex
      membranes.
AB  - We isolated forms of enveloped vaccinia virus from infected HeLa cells to obtain
      membranes for the analysis of lipids of the cis-Golgi network and trans-Golgi
      network. The intracellular mature virus obtains its envelope by wrapping itself
      in the membranes of the cis-Golgi network. A fraction of these virions then
      acquires a second envelope by enwrapping trans-Golgi network membranes to form
      the intracellular enveloped virus. Lipids were analyzed by high performance thin
      layer chromatography and digital densitometry to establish a steady-state lipid
      profile of viral membranes, which should reflect the compositions of the cis
      Golgi network and trans-Golgi network. Phosphatidyl-inositol was slightly
      enriched in the cis-Golgi network of HeLa cells, whereas the trans-Golgi network
      showed a minor increase in phosphatidylserine and sphingomyelin. Similarly,
      cholesterol was only slightly more abundant in the trans-Golgi compared to the
      cis-Golgi. An unusual lipid, semilysobisphosphatidic acid, was present in
      significant amounts in vaccinia envelopes. Semilysobisphosphatidic acid was
      present in similar levels in infected and uninfected cells, and was therefore not
      induced by vaccinia infection. Subcellular fractionation of HeLa cells indicated
      that the recovery of semilysobisphosphatidic acid paralleled the recovery of a
      Golgi marker. Furthermore, a lipid species that comigrated with
      semilysobisphosphatidic acid was also present in lipids extracted from highly
      purified, intact Golgi complexes from rat liver. Together, these results suggest
      that semilysobisphosphatidic acid is a normal component of Golgi membranes.

PMID- 8856509
TI  - The basolateral sorting signal of the polymeric immunoglobulin receptor contains
      two functional domains.
AB  - Basolateral sorting of the polymeric immunoglobulin receptor (pIgR) expressed in
      Madin-Darby canine kidney (MDCK) cells is mediated by a 17-residue sorting signal
      that resides in the cytoplasmic domain. We have recently analyzed the sequence
      requirements of the signal by alanine scanning mutagenesis. We found that
      basolateral sorting is mediated primarily by three amino acids: H656, R657 and
      V660. Individual mutations of each of these residues to Ala caused a substantial
      decrease in basolateral sorting and a corresponding increase in targeting to the
      apical surface. Structural analysis of 17-residue peptides corresponding to the
      signal revealed that V660 is in a beta-turn (probably type I) secondary
      structure, and its mutation to Ala destabilized the turn. H656 and R657 were not
      part of the turn and substitution of Arg657 to Ala had no effect on the turn
      stability. These results suggested that the signal is comprised of two
      structurally distinct domains: a critical V660 in the context of the beta-turn
      and an additional two residues (H656 and R657) that are not in the turn and
      probably are unimportant for its stability. Here we provide evidence suggesting
      that the two domains are distinguishable not only by their structure but also by
      their function. Basolateral targeting of pIgR mutants bearing Ala mutations at
      either 656 or 657 was not affected by treatment with brefeldin A (BFA), while
      basolateral targeting of pIgR containing an Ala substitution at position 660 was
      markedly and uniquely stimulated by BFA. Compared to single Ala substitutions,
      simultaneous mutations of H656 and R657 to Ala caused an additional minor effect
      on basolateral and apical sorting, whereas double mutations of V660 and either
      H656 or R657 resulted in a maximal decrease in basolateral targeting and
      corresponding increase in apical targeting. These results suggest the existence
      of two domains in the signal. When both domains are destroyed, basolateral
      targeting is maximally inhibited. The results also imply that V660 mediates
      basolateral sorting by a different mechanism from H656 and R657. We suggest that
      V660 and perhaps more generally the beta-turn may interact with BFA-sensitive
      adaptor complexes.

PMID- 8856510
TI  - Desmoplakin expression and organization at human umbilical vein endothelial cell
      to-cell junctions.
AB  - Desmoplakin is an intracellular component of desmosomes which plays a role in the
      anchorage of intermediate filaments to these structures. We report here that,
      despite the absence of desmosomes, cultured endothelial cells from human
      umbilical vein express desmoplakin I and II both at mRNA and protein level.
      Desmoplakin I/II are found only in the detergent insoluble fraction suggesting
      that most of the protein is linked to the cytoskeleton. Desmoplakin I/II could be
      detected by western blot only in long confluent cells even if desmoplakin mRNA
      levels are unchanged by cell confluency. This suggests that desmoplakin might be
      stabilized at protein level by its association with junctional components.
      Immunofluorescence confocal microscopy showed that desmoplakin codistributes with
      VE-cadherin and plakoglobin along the lateral cell membrane. In contrast,
      desmoplakin localization was distinct from that of PECAM, an endothelial specific
      junctional protein localized outside adherence junctions. Endothelial cells do
      not have keratins but they express vimentin. In confluent cells vimentin forms
      peripheral filaments which attach to the cell membrane in areas at desmoplakin
      localization. These data suggest that desmoplakin may participate in the
      molecular organization of interendothelial junctions by interacting with VE
      cadherin and promoting vimentin anchorage. This new type of intercellular
      junction seems to correspond to the "complexus adhaerentes' described in vivo in
      lymphatic endothelium.

PMID- 8856511
TI  - Focal cellular origin and regulation of interstitial collagenase (matrix
      metalloproteinase-1) are related to menstrual breakdown in the human endometrium.
AB  - Recent studies suggest that interstitial collagenase (MMP-1) is an essential
      enzyme in the early events leading to menstruation. This study analyses its
      cellular origin, regulation and relation to extracellular matrix breakdown in the
      human endometrium, both in cultured and non-cultured samples. The source of MMP-1
      was identified by in situ hybridization and by immunohistochemistry on serial
      sections. This was compared with the immunolocalization of other MMPs, steroid
      receptors, macrophages, and laminin. In non-cultured endometrium, MMP-1 was only
      expressed during the perimenstrual period. It was either restricted to
      superficial foci of stromal cells or extended towards the entire functional
      layer. MMP-1 expression remarkably correlated with matrix breakdown, as assessed
      by silver staining, and was prominent at the periphery of shedding fragments and
      along some arterioles. In cultured non-menstrual explants, MMP-1 expression was
      induced within two days after deprivation of sex steroids. Both in cultured and
      non-cultured samples, progesterone receptors were not detectable in epithelial
      cells at foci of MMP-1 expression. The same stromal cells could synthesize MMP-1,
      MMP-2 (gelatinase A) and MMP-3 (stromelysin-1), as well as laminin, and did not
      correspond to macrophages. In conclusion, MMP-1 is focally expressed in stromal
      cells of the functional layer of the endometrium, when and where steroid
      receptors disappear, and especially where tissue breakdown is prominent. These
      observations point to an essential role for MMP-1 in the early stages of
      menstruation.

PMID- 8856513
TI  - Dot-like focal contacts in adherent eosinophils, their redistribution into
      peripheral belts, and correlated effects on cell migration and protected zone
      formation.
AB  - We have examined the organization of F-actin and focal contacts in eosinophils
      and the functional consequences correlated with their predistribution. In
      activated eosinophils adherent to laminin, F-actin is localized in large,
      uniformly distributed, dot-like structures. Co-localized with the F-actin are a
      variety of typical components of focal contacts including: the alpha 6 and beta 1
      integrins subunits (which mediate eosinophil adhesion to laminin), vinculin,
      talin, pp125FAK, paxillin, and tyrosine phosphorylated proteins, but not the beta
      2 integrin subunit which is not involved in eosinophil adhesion to laminin. In
      unactivated eosinophils on laminin (which do not adhere well) and in activated
      eosinophils on non-adhesive surfaces (human serum albumin, tenascin, or a mixture
      of tenascin and laminin), dot-like accumulations of F-actin do not form. When
      activated eosinophils are incubated on laminin in the presence of low
      concentrations of 1,1'-ethylidenebis(L-tryptophan), a remarkable rearrangement
      occurs. Both conventional and confocal microscopy suggest that the dot-like
      structures rearrange from a uniform distribution into thick, peripheral belts
      surrounding each cell with few dot-like structures internal to the belt.
      Functional consequences occur as a result of this rearrangement of focal contacts
      and the cytoskeleton. The belt of focal contacts acts as a size-dependent
      permeability barrier; fluorescent 8 kDa polyethylene glycol does not label the
      substrate underneath the cells whereas 3.5 kDa polyethylene glycol labels the
      substrate uniformly. The formation of belts of focal contacts also blocks the
      ability of eosinophils to migrate on laminin in response to a chemotactic
      gradient. While the mechanism of 1,1'-ethylidenebis(L-tryptophan) action remains
      to be determined, experiments indicate that the function of 1,1'-ethylidenebis(L
      tryptophan) is distinct from the function of drugs that alter tyrosine kinase and
      serine/threonine kinase activities. Our observations reveal a novel mechanism for
      regulating cell behavior in invasive cells in which the rearrangement of focal
      contacts and the associated cytoskeleton may control cell migration and the
      sequestration of secreted cytotoxic and degradatory molecules. We propose that
      1,1'-ethylidenebis(L-tryptophan) may mimic the function of an endogenous
      regulator of eosinophil morphology and behavior.

PMID- 8856512
TI  - Contrasting migratory response of astrocytoma cells to tenascin mediated by
      different integrins.
AB  - Tenascin, an extracellular matrix protein, is expressed in human gliomas in vitro
      and in vivo. The distribution of tenascin at the invasive edge of these tumors,
      even surrounding solitary invading cells, suggests a role for this protein as a
      regulator of glioma cell migration. We tested whether purified tenascin,
      passively deposited on surfaces, influenced the adhesion or migration of a human
      gliomaderived cell line, SF-767. Adhesion of glioma cells to tenascin increased
      in a dose-dependent fashion up to a coating concentration of 10 micrograms/ml.
      Higher coating concentrations resulted in progressively fewer cells attaching.
      Cell adhesion could be blocked to basal levels using anti-beta 1 integrin
      antibodies. In contrast, when anti-alpha v antibodies were added to the medium of
      cells on tenascin, cell adhesion was enhanced slightly. Using a microliter scale
      migration assay, we found that cell motility on tenascin was dose dependently
      stimulated at coating concentrations of 1 and 3 micrograms/ml, but migration was
      inhibited below levels of non-specific motility when tested at coating
      concentrations of 30 and 100 micrograms/ml. Migration on permissive
      concentrations of tenascin could be reversibly inhibited with anti-beta 1, while
      treatment with anti-alpha v antibodies increased migration rates. We conclude
      that SF-767 glioma cells express two separate integrin receptors that mediate
      contrasting adhesive and migratory responses to tenascin.

PMID- 8856514
TI  - Cytokinesis in Aspergillus nidulans is controlled by cell size, nuclear
      positioning and mitosis.
AB  - The mycelium of Aspergillus nidulans is composed of multinucleate cellular
      compartments delimited by crosswalls called septa. Septum formation is dependent
      on mitosis and requires the recruitment of actin to the site of septum formation.
      Employing a collection of temperature sensitive nuclear distribution (nudA2,
      nudC3 and nudF7), nuclear division (nimA5, hfaB3), and septation (sepD5, sepG1)
      mutants, we have investigated the interdependency among nuclear positioning,
      mitosis, and cell growth in structuring the cellular compartments of A. nidulans.
      The cellular compartments of nud+ strains were highly uniform with regard to
      nuclear distribution and averaged 38 microns in length. Incubation of nud mutants
      at semi-restrictive temperature resulted in aberrant nuclear distribution that
      appeared to direct the formation of variable-sized cellular compartments, ranging
      from 5 microns to greater than 81 microns. In germinating spores, the first
      septum forms at the basal end of the germ tube following the third round of
      nuclear division. Germlings must undergo mitosis in order to form a septum.
      Temperature-sensitive mitotic mutants were used to show that a single nuclear
      division is sufficient to activate septum formation, provided a critical cell
      size has been attained. In mitotic mutants and wild-type cells, delays in nuclear
      division resulted in the misplacement of the first septum. These results strongly
      support the role of mitotic nuclei in determining septal placement, and suggest
      that cell size control is post-mitotic in A. nidulans.

PMID- 8856515
TI  - Validation of a measure for adolescent self-report of attention deficit disorder
      symptoms.
AB  - The internal consistency, criterion-related, and concurrent validity of the ADD/H
      Adolescent Self-Report Scale was evaluated using 150 adolescent males ages 12 to
      17 years; 103 cases were diagnosed with attention-deficit hyperactivity disorder
      (ADHD) and 47 with no known psychiatric condition. Participants completed the
      ADD/H Adolescent Self-Report Scale; their mothers completed the Conners Parent
      Questionnaire and Child Behavior Checklist. For the ADD/H Adolescent Self-Report
      Scale, Cronbach's alpha coefficients ranged from .81 to .91. Criterion-related
      validity was established when it was found that ADHD adolescents reported
      significantly more problems than controls on all 11 scales. Concurrent validity
      was established through the finding of moderately strong correlations between
      comparable scales of the adolescent and parent measures.

PMID- 8856516
TI  - A firearm safety program for children: they just can't say no.
AB  - The purpose of this study was to compare children's play and aggressive behavior
      with firearms before and after an information-based intervention. Correlates of
      aggression and gun play were also analyzed. Subjects were 24 pairs of preschool
      children videotaped for 10 minutes in a structured play setting, in which they
      had access to a variety of toys and to real and toy guns. One child from each
      dyad was then exposed to an information-based intervention and told not to play
      with guns. The children were again videotaped in the same setting approximately 1
      week later. Results indicated that the intervention was ineffective in modifying
      the behavior of the children. Regression analyses revealed that access to a
      parent's firearm was correlated with gun play and that gun play and handling of
      firearms in the home were correlated with aggressive behavior. The findings in
      this study represent the first systematic attempt to decrease gun play in
      children and suggest that information provision alone is an insufficient
      intervention.

PMID- 8856517
TI  - The 2-year stability of parental perceptions of child vulnerability and parental
      overprotection.
AB  - Clinicians often identify parent-child relationships that are believed to be
      problematic for the child's future emotional growth, yet there are minimal
      outcome data on which to base anticipatory guidance. This 2-year follow-up study
      examined the stability and child behavioral correlates of parental perceptions of
      increased child vulnerability and parental overprotection. Of 192 potential
      participants, 114 parents (93% mothers, 86% white, 75% married, 90% middle-upper
      socioeconomic status) with children age 4 to 7 years successfully completed the
      Parent Protection Scale, Child Vulnerability Scale, Child Behavior Checklist 4
      18, and the Parental Bonding Instrument. The 2-year stability of high parental
      overprotection was 37%; for high parental perception of child vulnerability, it
      was 31%. High perceived vulnerability at enrollment was significantly associated
      with both internalizing (somatic complaints, anxious/depressed) and externalizing
      (aggressive) behaviors at follow-up. A history of overprotection in the parent's
      childhood was not associated with current parental report of overprotective
      behaviors toward the child.

PMID- 8856518
TI  - Children and adolescents with neurofibromatosis 1: a behavioral phenotype.
AB  - Twenty 6- to 17-year-old children with neurofibromatosis 1. (NF1) were compared
      to 20 age- and sex-matched siblings on a wide range of neuropsychological and
      behavioral dimensions. In familial cases, diagnostic status was confirmed by gene
      linkage with greater than 98% accuracy. Visual examinations that included
      assessments of visual evoked responses (VER) were performed on subjects with NF1.
      Forty-two percent of NF1 subjects had abnormal VER and underwent magnetic
      resonance imagery or computed tomography scans of the brain. On a variety of
      skills, subjects with NF1 performed more poorly than unaffected siblings.
      Children with NF1 were found to be less competent on measures of cognitive,
      language, and motor development, visual-spatial judgment, visual-motor
      integration, and academic achievement. Learning disabilities were common in
      children with NF1. Parents and teachers reported that NF1 subjects had
      internalizing problems and difficulty interacting with peers. A behavioral
      phenotype for NF1 and recommendations for preventative interventions are
      proposed.

PMID- 8856519
TI  - Effects of prenatal exposure to opioids on focused attention in toddlers during
      free play.
AB  - The goals of this study were: (1) to determine if 24-month-old children exposed
      to opioids show decreased focused attention during free play compared with
      children of the same age who were not prenatally exposed; (2) to identify medical
      and social risk factors other than drug exposure that are related to focused
      attention; and (3) to determine if mothers' teaching ability had an effect on
      attention. Focused attention was rated during a 3-minute free play session for 30
      toddlers who were methadone-exposed and for 44 comparison toddlers. The mother
      teaching the child to use a toy was also rated separately from the free play
      session. There was no difference in focused attention of 24 month olds during
      free play based only on prenatal exposure. Despite group differences in medical
      and social risk factors, only maternal IQ was significantly related to focused
      attention. Maternal instruction was strongly related to focused attention and
      mediated the effects of maternal IQ on attention.

PMID- 8856520
TI  - Initiation of cigarette smoking among children with and without learning
      disabilities.
AB  - The goals of this study were to determine if: (1) children with learning
      disabilities should be included in school-based smoking prevention programs and
      (2) existing prevention curricula are appropriate for children with learning
      disabilities. Initiation of cigarette smoking and several correlates of smoking,
      including personal attribute, peer influence, and parent influence variables,
      were measured in a sample of 1470 3rd and 5th grade children. The rates of
      smoking initiation were 17% and 15% for children with and without learning
      disabilities, respectively. In addition, several of the known correlates of
      smoking among youth, including low self-control, negative orientation toward
      school, and peer smoking, were also significantly associated with smoking by
      children with learning disabilities. Children with learning disabilities are as
      much in need of smoking prevention programs as children without learning
      disabilities. Although current smoking prevention curricula address issues
      relevant to children with learning disabilities, additional research is needed to
      identify the special needs of these children and to determine the type of smoking
      prevention program most likely to be effective with them.

PMID- 8856521
TI  - Attention-deficit hyperactivity disorder: sometimes a disorder, often a clinical
      tautology.

PMID- 8856522
TI  - Searching for solutions: the importance of including teenagers in the research
      process.

PMID- 8856523
TI  - Drug rehabilitation in a treatment farm setting: the Nitawgi farm experience,
      1978-1990.

PMID- 8856524
TI  - Maria: stubborn, willful, and always full of energy.

PMID- 8856526
TI  - Challenging case: Beyond infant colic.

PMID- 8856525
TI  - Schools, families, and early adolescents: what are we doing wrong and what can we
      do instead?
AB  - Although most individuals pass through adolescence without excessively high
      levels of "storm and stress," many individuals experience difficulty during this
      period. Why? Is there something unique about this developmental period that puts
      individuals at greater risk for difficulty? This paper focuses on these questions
      and advances the hypothesis that some of the "negative" psychological and
      behavioral changes associated with adolescent development result from a mismatch
      between the needs of developing adolescents and their experiences at school and
      at home. It provides theoretical and empirical examples of how this mismatch
      develops, how it is linked to negative age-related changes in early adolescents'
      motivation, self-perceptions, self-evaluations, and psychological competence, and
      how we could provide more developmentally appropriate social environments,
      particularly at school.

PMID- 8856527
TI  - Total wrist fusion. A functional assessment.
AB  - Twenty cases of total wrist fusion, performed for post-traumatic conditions, were
      reviewed objectively, subjectively and radiologically. All patients were
      satisfied with the position of the fused wrist and had good pain relief. All
      patients would have had the procedure sooner, having had an average of three
      operations on the wrist before the fusion. There was a high complication rate
      (45%), although only four patients required further procedures for those
      complications. Hand function, as assessed by the Jebsen and Purdue tests, was
      found to be poor; this may be due to a reduced range of finger movements. There
      was no correlation between position of fusion, carpal height or number of joints
      radiologically fused, and the pain score, grip strength or Buck-Gramcko score.

PMID- 8856528
TI  - A modified dorsal approach to the wrist for arthrodesis of the non-rheumatoid
      wrist. An anatomical study.
AB  - Fourteen cadaveric wrists were dissected to investigate a modified dorsal
      approach that involved osteotomy of the small and dorsal tubercles without
      opening the third compartment. This approach could be safely made with good
      exposure of the dorsum of the wrist. The mean normal angle formed by the extensor
      pollicis longus tendon at the level of the dorsal tubercle was 144 degrees. An
      approach that involves division of the third compartment may lead to effective
      lengthening of the extensor pollicis longus musculotendinous unit by 8 to 17 mm
      with corresponding decrease in the tension generated by its contraction. The
      modified approach permits restoration of the normal alignment of the extensor
      pollicis longus tendon, and may be useful for performing arthrodesis of the non
      rheumatoid wrist in young manual workers.

PMID- 8856529
TI  - Wrist arthrodesis using a dynamic compression plate.
AB  - In order to determine the effectiveness of wrist arthrodesis using dynamic
      compression plating and bone grafting, we reviewed 18 consecutive procedures in
      17 patients performed using a standardized technique over a 6-year period.
      Fourteen patients had previously undergone an average of 2.1 operations prior to
      arthrodesis. Mean follow-up was 48 months. All but one patient reported
      considerable pain relief and were satisfied with their results. Grip strength
      remained limited compared to the contralateral wrist. Complications were limited
      to one case of reflex sympathetic dystrophy and metacarpophalangeal joint
      contracture, and minor problems related to the bone graft donor site.

PMID- 8856530
TI  - The role of arthroscopy in the investigation of wrist disorders.
AB  - The findings at arthroscopy of the wrist in 48 consecutive cases carried out over
      a 4.5 year period have been retrospectively reviewed. In correlating the clinical
      and arthroscopic findings in the 36 patients with wrist instability and
      triangular fibrocartilage injuries we found concurrence in 28 of the cases. In
      the six patients in whom we were unable to make any provisional clinical
      diagnosis we did not find arthroscopy helpful. Arthroscopy usefully influenced
      the management in two of the six patients in whom the articular surface was
      assessed. We feel that a careful clinical examination of the wrist is the
      mainstay of diagnosis in wrist disorders. Arthroscopy remains useful in selected
      cases but has a limited specialized role which should continue to be provided
      from specialist centres.

PMID- 8856531
TI  - Combined fracture of the hook of the hamate and palmar dislocation of the fifth
      carpometacarpal joint.
AB  - A case of fracture of the hook of the hamate associated with a palmar dislocation
      of the fifth carpometacarpal joint is described. Surgical exploration revealed
      that the different elements of the flexor carpi ulnaris musculotendinous unit,
      which includes the pisiform, the pisohamate and pisometacarpal ligaments, were
      displaced proximally together with the avulsed fragment of the hook of the hamate
      and the fifth metacarpal. These findings suggest that such an injury results from
      a sudden, violent contraction of the flexor carpi ulnaris against the fixed
      wrist. It was successfully treated by open reduction and fixation of the hook of
      the hamate fracture and stabilization of the carpometacarpal joint.

PMID- 8856532
TI  - The capitohamate ligaments. A comparison of biomechanical properties.
AB  - The physical attributes of the three capitohamate interosseous ligaments were
      tested in a computer-controlled multi-axis testing machine using 12 human cadaver
      specimens. After an intact test run, selected ligaments were cut in random
      sequence and the test repeated. The remaining ligaments were tested to failure
      with servohydrolic stress at 5 mm/second. In the intact joint complex, the
      average dorsopalmar rotational displacement was approximately 9 degrees in each
      direction. Under the load limit, the dorsopalmar translational displacement
      averaged 0.9 mm and 0.5 mm respectively, proximal-distal translational
      displacement averaged 0.8 mm and 0.4 mm respectively, and distractional
      displacement averaged 0.3 mm. Based on the sequential sectioning it was found
      that the dorsal ligament provided 76% (SD 14) of the rotational resistance with
      palmar rotation of the capitate and 44% (SD 19) of translational constraint with
      palmar translation of the capitate. The deep ligament provided 51% (SD 15) of the
      rotational resistance with dorsal rotation of the capitate and 63% (SD 24) of
      translational resistance with dorsal translation of the capitate. With proximal
      distal translation, the dorsal ligament was the most important constraint in each
      direction. In resisting distraction, each of the three ligaments was equally
      effective. Failure testing showed the deep ligament was strongest at 289 N,
      followed by the palmar at 171 N and the dorsal at 133 N.

PMID- 8856533
TI  - The Galeazzi-equivalent lesion in children revisited.
AB  - A fracture at the medial end of the distal third of the radius with an epiphyseal
      separation of the distal ulna in a 16-year-old boy is described. This injury,
      known as the Galeazzi-equivalent lesion in children, is characterized by complete
      distal ulnar epiphyseal separation without rupture of the distal ligamentous
      stabilizing system between the radius and ulna, which includes the triangular
      fibrocartilage complex, interosseous ligaments and periosteal tube of the ulnar.
      The Galeazzi fracture-dislocation and the Galeazzi-equivalent lesion appear to be
      completely dissimilar in their pathological anatomy. We suggest calling the
      latter a "pseudo-Galeazzi injury".

PMID- 8856534
TI  - Excision of the trapezium for osteoarthritis of the trapeziometacarpal joint of
      the thumb.
AB  - We assessed the results of 86 trapeziectomies in 83 patients. Simple excision of
      the trapezium was performed in 54 thumbs. This was combined with shortening of
      the abductor pollicis longus tendon in 14 thumbs and with soft-tissue
      interposition and/or ligamentous reconstruction in 17 thumbs. 88% of the patients
      were satisfied with the result, 76% had relief of pain and 74% had no functional
      disability. The subjective results achieved with the three different techniques
      were similar. Clinical assessment of 57 thumbs revealed no statistical difference
      in web span, thumb adduction-flexion, key pinch and grip strength between the
      three operative procedures, nor in comparison with the non-operated contralateral
      hand.

PMID- 8856535
TI  - The direct midlateral approach with lateral enlargement of the pulley system for
      repair of flexor tendons in fingers.
AB  - The direct midlateral approach and the lateral enlarging procedure of the pulley
      system have been utilized in our service since 1972. The incision runs directly
      behind the neurovascular pedicle, which is left in the palmar skin flap of the
      anterior compartment of the finger, in order to ensure its blood supply and
      sensibility. The transverse digital lamina of Landsmeer's skin anchoring system
      and Cleland's ligament are preserved and are used to perform a lateral
      enlargement of the pulleys after tendon repair. The technique allows wide
      surgical exposure of the digital fibro-osseous tunnel, enlargement and
      reconstruction of the pulley system and tendon sheath, flexor tendon repair
      (using the technique of choice) and reduces postoperative impingement in zone 2.

PMID- 8856537
TI  - Mechanical properties of various circumferential tendon suture techniques.
AB  - We evaluated the mechanical properties of six different circumferential tendon
      sutures with a variable number of suture strands. Seventy-two human cadaver
      flexor profundus tendons were cut and repaired using only a 6/0 polypropylene
      circumferential suture. The six running suture techniques were: Simple; Simple
      locking; Lembert; Halsted; Cross-stitch; Lin-locking; using 10, 14 and 18 suture
      passes. The increased suture passes increased both tensile and gap strengths. The
      tensile strength of the Lin-locking technique (29 to 63 N) was significantly
      stronger than the others, followed by Cross-stitch (27 to 38 N), Halsted (21 to
      27N), Lembert (20 to 27N), Simple (11 to 22 N) and Simple-locking (10 to 17 N).
      The gap strength values were between 3 to 14N, with no significant differences
      between the techniques. The resistance to gliding, as measured by work of
      flexion, was not affected by the number of strands. However, the Lin-locking
      significantly increased the resistance to gliding (33-36%) compared to the other
      techniques (6-21%); there were no significant differences between these five
      techniques.

PMID- 8856536
TI  - Colour doppler ultrasound examination of hand tendon pathologies. A preliminary
      report.
AB  - Apart from real-time sonography, in most of the imaging techniques used to
      examine the musculoskeletal system, such as X-ray, computerized tomography scan
      and magnetic resonance imaging produce mainly static images. Although colour
      Doppler imaging (CDI) is generally used in the examination of blood flow, it may
      offer the opportunity to study the dynamic characteristics of tendons and
      muscles. The purpose of this study was to examine the unilateral flexor and
      extensor tendon pathologies of the hand and compare these images with the healthy
      side. A Phillips Quantum Doppler was used to study patients with tendon adhesions
      and trigger finger. The normal and pathological tendons were scanned at three
      anatomical levels: wrist, metacarpal and proximal phalanx. The results obtained
      from the comparison of pathological images with normal ones indicate that CDI
      offers a promising approach to image dynamically and, in the future, to quantify
      the function of the tendons and muscles in the musculoskeletal system and to
      define their pathologies.

PMID- 8856538
TI  - Dupuytren's disease occurring after a surgical injury to the hand.
AB  - We report three clinical cases in which Dupuytren's disease was triggered by
      surgical trauma. All patients developed the contracture between 3 weeks and 3
      months after operation for unrelated pathology of the hand. They had significant
      swelling of the hand postoperatively, preventing full mobilization. They did not
      have a strong diathesis for the disease. Since the appearance of the contracture,
      they have not developed the disease in the contralateral hand or anywhere else in
      the body. In one case, a similar operation on the contralateral band has not
      provoked onset of the disease.

PMID- 8856539
TI  - Dupuytren's disease treated by palmar fasciectomy and an open palm technique.
AB  - The results of long-term follow-up (range 9-19 years) are presented in a
      continuous series of patients treated for Dupuytren's contracture by one surgeon
      using the open palm technique. Mean preoperative total range of movement was 48%
      rising to 96% postoperatively. Mean total range of movement was 92% at follow-up.
      Survivorship analysis revealed 86% survival at 10 years and 77% survival at 19
      years. There was one digital nerve injury and one case of algodystrophy. This
      technique gives good long-term results without the use of night splintage or
      physiotherapy.

PMID- 8856540
TI  - Simultaneous tendon transfer and autogenous augmentation of the first web space
      of the hand with intrinsic paralysis.
AB  - Simultaneous tendon transfer and dermofat graft augmentation of the first web
      space of the hand with intrinsic paralysis is described. Fifty per cent over
      correction of the web space volume is recommended in anticipation of
      postoperative graft resorption. Other techniques of fat auto-transplantation are
      discussed.

PMID- 8856541
TI  - High resolution magnetic resonance imaging of the proximal interphalangeal
      joints. Correlation with histology and production of a three-dimensional data
      set.
AB  - The magnetic resonance imaging appearance of the proximal interphalangeal joints
      of cadavers was correlated with histology of the same specimen allowing many
      small-scale features to be identified that might otherwise have been
      misinterpreted. It enabled the magnetic resonance signal to be understood at a
      tissue and cellular level, allowing identification of synovial folds extending
      from the extensor tendon and volar plate, the entheses of the proper collateral
      ligament, the epitenon of the flexor tendons and the presence of osteophytes and
      sites of cartilage erosion. The main difficulties in matching two-dimensional
      magnetic resonance images with histology were the differing section thicknesses
      of the two methods and shrinkage of histological specimens. There are many
      advantages in producing high resolution three-dimensional datasets-the magnetic
      resonance section thickness is reduced and the individual components of the joint
      can be viewed simultaneously in two or more planes. A unique magnetic resonance
      atlas of three dimensional joint structure is presented.

PMID- 8856542
TI  - Apparent and partial non-union of the scaphoid.
AB  - Ten patients with radiological non-union of the scaphoid and four patients with
      suspected non-union were explored surgically. At operation, ten scaphoids looked
      united; five of these went on to definite union but the other five to non-union
      (in one case, despite a Herbert screw). In another four patients, there appeared
      at operation to be partial union; all proceeded to complete union. Even with the
      scaphoid in front of you, it can be difficult to decide whether it has united or
      not.

PMID- 8856543
TI  - The unstable capitolunate and radiolunate joints as a source of wrist pain in
      young women.
AB  - A retrospective study of 12 young women (14 cases) complaining of chronic wrist
      pain, obscure numbness and reduction of grip strength is presented. The average
      duration of the complaints was 7.3 years. All wrists were in VISI alignment, with
      normal motion series and normal intrinsic interosseous ligaments demonstrated
      arthrographically. The dorsal-displacement stress test showed subluxation of the
      capitolunate (in nine cases) or both the capitolunate and the radiolunate joints
      accompanied by a marked feeling of apprehension. Surgical management consisted of
      ligamentous reefing of the whole palmar aspect of the midcarpal joint and the
      radiolunate joint when needed. Additionally, a neurectomy of the terminal branch
      of the anterior interosseous nerve was done in four cases. The result was
      excellent in eight cases, good in five cases and fair in 1 case. Young women with
      "delicate" wrists and obscure wrist pain may have isolated instabilities of the
      capitolunate and radiolunate joints. In cases that do not respond to conservative
      measures ligamentous reefing should be considered.

PMID- 8856544
TI  - Biodegradable pins versus Kirschner wires in hand surgery.
AB  - We compared biodegradable pins with standard Kirschner wires in the fixation of
      fractures, arthrodeses and osteotomies in the hand in a prospective, randomized
      study. Eleven patients were allocated to the biodegradable pin group and 12 to
      the Kirschner wire group. Age, gender, operative procedure and postoperative
      treatment did not differ in the two groups. All patients were evaluated after 6
      months. No differences in time to union or complication rates were found, but the
      number of additional operative procedures in the Kirschner wire group
      significantly exceeded the number needed in the biodegradable pin group.

PMID- 8856545
TI  - Irreducible fracture of the neck of the fifth metacarpal.
AB  - We report a rare case of fracture of the neck of the fifth metacarpal which
      required open reduction. The radial and ulnar collateral ligaments entrapped the
      displaced metacarpal head. This patho-anatomy resembles that of rotational
      supracondylar fractures of the proximal phalanx.

PMID- 8856546
TI  - Nerve growth factor enhances nerve regeneration through fibronectin grafts.
AB  - Soluble fibronectin and nerve growth factor (NGF) promote axonal regeneration
      when placed in silicone tubes. We investigated the ability of orientated
      fibronectin mats to bind and release bioactive NGF and the possibility of
      augmenting axonal regeneration following axotomy by using fibronectin conduits
      impregnated with NGF. The release of NGF was quantified using a fluorometric
      ELISA and bioactivity confirmed with a neuronal culture bioassay.
      Immunohistochemical techniques and computerized image analysis were used to
      assess the rate and volume of axonal and Schwann cell regeneration. The delivery
      of NGF to the site of injury produced an increase in the rate (P < or = 0.007)
      and volume (P < or = 0.004) of both axonal and Schwann cell regeneration when
      compared to conduits of plain fibronectin. We conclude that the local delivery of
      NGF by impregnated fibronectin conduits enhances axonal regeneration.

PMID- 8856547
TI  - Tennis elbow: treatment of resistant cases by denervation.
AB  - Anatomical and clinical research has shown that the entire lateral epicondylar
      region is innervated only by radial nerve branches. Based on these investigations
      we have developed a surgical procedure for complete denervation which is
      indicated only in resistant cases of tennis elbow. Only one nerve pathway calls
      for careful exposure, otherwise denervation is accomplished blindly by
      disinsertion of certain muscles. The result of this procedure also depends on
      simultaneous indirect decompression of the posterior interosseous nerve.
      Excellent or good results were obtained in 90% on average. Results of denervation
      did not improve by additional direct radial nerve release.

PMID- 8856548
TI  - Closure of wounds in the upper extremity using a skin stretching device.
AB  - A skin stretching device (SSD) harnessing the viscoelastic properties of skin
      using incremental traction has been used in 20 patients with skin deficits in the
      upper extremity. Complications were few considering the extensive damage to the
      skin and included slight partial dehiscence, necrosis of skin edges, local
      infection and hypertrophic scars. All wounds healed without the need for further
      surgical procedures. Application of the SSD is simple and it can even be used at
      the bedside under local anaesthesia. It reduces the need for more complicated
      surgical procedures like grafts or flaps.

PMID- 8856549
TI  - Flexor tenosynovectomy and tenolysis in longstanding rheumatoid arthritis.
AB  - A total of 43 patients (49 hands; 424 flexor tendons), who had rheumatoid
      arthritis of more than 15 years duration at the time of surgery, were clinically
      assessed at a mean follow-up of 5.7 years (range, 1.2-12 years). Pain and
      inability to flex actively despite a good passive range of motion were the main
      surgical indications. The results suggest that the patients had excellent
      sustained pain relief (mean score = 0.9) and were highly satisfied with the
      outcome of the procedure (mean score = 2.2). 81% had adequate pulp-to-pulp and
      key pinch. Range of finger motion (total active motion, TAM) was excellent to
      good in 45% and fair in 22%. Thirty-three per cent were graded as poor and these
      were found to be multifactorial in origin, with associated significant joint
      disease, preoperative tendon ruptures, extensive digital surgery, readhesions and
      combinations of operative procedures which adversely affect the rehabilitation
      programme. Flexor tenosynovectomy with tenolysis is a useful procedure with a low
      rate of recurrence.

PMID- 8856550
TI  - Metastases to the hand from carcinoma of the lower alveolus.
AB  - A case of carcinoma of the lower alveolus metastasizing to the phalanges of the
      hand is reported. The possible mechanism of such metastases, the clinical and
      radiological features and the role of fine needle aspiration cytology are
      discussed.

PMID- 8856551
TI  - Metastatic tumours of the hand. Report of six additional cases.
AB  - Six metastatic tumours of the hand are reported. Five were located in long bones
      of the hand and one in the soft tissues without bone involvement. The primary
      tumours arose in the lung, kidney, hard palate, larynx and pharynx. Treatment was
      palliative and consisted of amputation for distal lesions and local excision
      and/or radiation for proximal lesions when symptomatic. Short-term prognosis was
      poor with a median survival of 7 months. In two patients, hand metastases were
      the first sign of malignant disease.

PMID- 8856552
TI  - Eccrine spiradenoma of the hand clinically mimicking a lipoma.
AB  - A rare case of eccrine spiradenoma of the hand is described. The tumour mimicked
      a lipoma on clinical examination and in macroscopic appearance. The
      classification and treatment of eccrine tumours are discussed.

PMID- 8856553
TI  - Carpal tunnel syndrome in amyotrophic lateral sclerosis and late onset cerebellar
      ataxia.
AB  - We report on clinical and electrophysiological findings and management in nine
      patients who developed carpal tunnel syndrome during the course of amyotrophic
      lateral sclerosis and late onset cerebellar ataxia, two neurodegenerative
      diseases. The patients were treated with surgical decompression (five cases) and
      local steroid injections (four cases). Only one showed lasting relief of symptoms
      and significantly improved distal conduction in the median nerve at follow-up
      after 2 to 3 months. The symptoms and conduction data remained unchanged in three
      patients who could be followed for more than 1 year. We think that axonal
      neuropathy plays an important role in the development of carpal tunnel syndrome
      in these patients and accounts for the failure of the standard treatments.

PMID- 8856554
TI  - Cubital tunnel syndrome caused by tophaceous gout.
AB  - We report a case of cubital tunnel syndrome caused by tophaceous gout. The ulnar
      nerve was compressed by a tophus at the distal cubital tunnel. Surgical
      decompression relieved the symptoms.

PMID- 8856555
TI  - Radial tunnel syndrome.

PMID- 8856556
TI  - Radial tunnel syndrome.

PMID- 8856557
TI  - Wrist denervation.

PMID- 8856558
TI  - Wrist denervation.

PMID- 8856559
TI  - A method of two-dimensional measurement for evaluating finger motion impairment.

PMID- 8856560
TI  - Review of carpal tunnel syndrome in children.

PMID- 8856561
TI  - Carpal tunnel syndrome in childhood.

PMID- 8856562
TI  - Dupuytren's disease.

PMID- 8856563
TI  - Rotation-angulation osteotomy in the hand.

PMID- 8856564
TI  - Body and soul.

PMID- 8856565
TI  - Practice analysis of hand therapy.
AB  - In 1994, a practice analysis (role delineation study) was conducted on the
      profession of hand therapy. This study was conducted as a follow-up to the
      original study conducted by the American Society of Hand Therapists (ASHT) in
      1985. A representative group of content experts developed a description of hand
      therapy practice, and this description was validated using a questionnaire. The
      questionnaire was distributed to a random sample of 400 certified hand therapists
      (CHTs), of whom 50% responded. The respondents provided confirmation of the
      accuracy of the description of hand therapy. The survey results were used to
      update the test specifications for the Hand Therapy Certification Examination.
      The results enabled the Hand Therapy Certification Commission to improve upon its
      certification program by clarifying and expanding the definition of hand therapy.
      The 1994 findings were also compared with the results of the 1985 study.

PMID- 8856566
TI  - The hand therapy certification examination: results of the first five years.
AB  - In 1991, the first Hand Therapy Certification Examination was administered to
      candidates throughout the United States. Since then, the examination has been
      given annually. The purpose of this paper is to summarize the processes that have
      been used to develop the examination as well as to report demographic data about
      the examination and certification candidates. Overall, the results of test
      administration have been very good. Twenty-two hundred therapists have become
      certified hand therapists. Eighty-five percent are occupational therapists, and
      88% are female. Most candidates have practiced for ten years or less and have
      maintained caseloads of upper-extremity patients for three to six years. The
      examination has performed well. Reliability coefficients have been 0.91 or
      greater for each administration. The mean scores on the examination have
      decreased each year, from 148.4 in 1991 to 129.4 in 1995.

PMID- 8856567
TI  - The abductores pollicis muscles. Clinical considerations based on
      electromyographical and anatomical studies.
AB  - The abductor pollicis longus (APL) muscle consists of two separate functional
      divisions with separate insertions. The muscle is composed of a deep and a
      superficial division. The APL and the abductor pollicis brevis (APB) are
      discussed in relation to assessment and clinical conditions on the basis of
      anatomic and electromyographic studies. It has been found that in some movements
      of the thumb and the hand, the function of the APL is related to the function of
      the APB, and vice versa. The APL is an important muscle for the function of the
      human thumb and hand, and knowledge of its function is important in clinical
      assessment and reconstructive surgery.

PMID- 8856568
TI  - Reliability of the manual dynamic mode of the Baltimore Therapeutic Equipment
      Work Simulator.
AB  - Twelve Baltimore Therapeutic Equipment Work Simulators (BTEWS) were tested for
      consistency of resistance in the manual dynamic mode using a previously described
      timed weight-drop test. Fifty weight-drop measurements were made at five
      different weight levels: 5, 10, 20, 30, and 40 lb. Alterations in weight-drop
      times indicate changes in exercise-head resistance. Substantial resistance
      variation was found in the manual dynamic mode. With console resistance set
      consistently at 92% of applied weight, weight-drop times varied from failures of
      the weight to drop to times that were not recognized by the electronic timing
      system. Measurable weight-drop times ranged from 0.75 to 16.97 seconds. Ten
      Simulators had weight-drop times greater than +/-3 standard deviations (SD) from
      the mean; eight Simulators had times +/-4 SD from the mean; and four had times +/
      5 SD from the mean. Console printout data did not accurately reflect resistance
      produced by the exercise head. While intermachine correlations based on Simulator
      printout data ranged from +1.0 to +0.9906, correlations derived from resistance
      based weight-drop times ranged from +0.9866 to -0.9956. For a constant externally
      applied torque, the weight-drop times should have been constant but were not.
      Resistance produced in the manual dynamic mode is inconsistent, both within and
      between machines (p = 0.0001).

PMID- 8856569
TI  - Principles of conservative management for a non-orthotic tenodesis grip in
      tetraplegics.
AB  - The effectiveness of a tenodesis grip is determined by the passive properties of
      the hand. An effective tenodesis grip can be achieved by encouraging a decrease
      in the resting length (i.e., adaptive shortening) of the flexor digitorum
      profundus and the flexor digitorum superficialis so that the fingers flex when
      the wrist is extended. Also, adaptive shortening of the flexor pollicis longus
      needs to be encouraged so that the thumb approximates the flexed fingers when the
      wrist is extended. The length of the adductor pollicis will in part dictate where
      along the radial side of the index finger the thumb will contact. Development of
      an effective tenodesis grip also requires that excessive metacarpophalangeal and
      interphalangeal joint stiffness of the fingers be prevented and that the
      interphalangeal joint of the thumb become stiff in extension. Careful management
      of the tetraplegic hand can ensure the development of the musculoskeletal changes
      necessary for an effective tenodesis grip.

PMID- 8856570
TI  - Training of muscle excursion after tendon transfer.
AB  - In tendon transfer (TT) surgery there is usually a discrepancy in excursion
      between the muscle(s) to be replaced and the transferred muscle(s). For example,
      in patients with radial palsy the pronator terres (PT) muscle is frequently used
      to replace the wrist extensors. However, the excursion of the PT is less than the
      extensor of the wrist and therefore needs to double its length to allow for full
      wrist movement. Questions arise about whether or not the PT will increase its
      fiber length after transfer for wrist extension and how therapy can positively
      influence usable excursion of the transferred muscle-tendon unit. Most
      classifications of results accept the flexion of the wrist will remain limited
      after TT of the PT. This article presents a patient with TT of the PT who
      accomplished a wrist total active range of motion (TAM) of 125 degrees (wrist
      extension 0-60 degrees, flexion 0-65 degrees). Based on this observation, the
      authors assume that the PT muscle has indeed increased its excursion after TT.
      The authors conclude that limited wrist excursion should not be accepted too
      soon, but therapists have to familiarize themselves with methods for "excursion
      training" and possibly change the existing methods of evaluating the results of
      TT of the PT.

PMID- 8856571
TI  - MP/PIP adjustable digit blocking splint.

PMID- 8856572
TI  - Adjustable first webspace splint.

PMID- 8856573
TI  - Interferon-alpha for viral hepatitis.
AB  - IFN-alpha has emerged as a promising treatment of chronic viral hepatitis.
      Although therapeutic response to IFN is far from universal, efficacy has been
      demonstrated; and studies combining IFN-alpha with other agents, as well as
      trials with new preparations of IFN-alpha, are under way. Children do not
      represent a large part of the identified population with chronic viral hepatitis.
      Yet children, by simple virtue of age, are more recently infected. In addition,
      longer life expectancies can be expected to be associated with greater morbidity
      from chronic viral hepatitis. Children seem to tolerate therapy with IFN-alpha
      well. Treatment of children with chronic viral hepatitis should be strongly
      considered, with protocols designed to ascertain specific pediatric safety and
      efficacy.

PMID- 8856574
TI  - Indications for pediatric gastrointestinal endoscopy: a medical position
      statement of the North American Society for Pediatric Gastroenterology and
      Nutrition.

PMID- 8856575
TI  - The 13C-octanoic acid breath test: a noninvasive technique to assess gastric
      emptying in preterm infants.
AB  - Gastric emptying (GE) is difficult to evaluate properly in preterm infants
      because of the lack of safe and reliable noninvasive methods. The 13C-octanoic
      acid breath test, a noninvasive method to assess GE, was validated in adults. The
      aim of this study was to adapt the methodology of the 13C-octanoic acid breath
      test regarding test meal and sampling methods and to define normal values for
      healthy preterm infants. We tested 11 clinically stable preterm infants who
      demonstrated normal fetal growth. The infants mean gestational age at birth was
      33 weeks, mean birth weight was 1754 g, mean postnatal age at the day of study
      was 26 days, and mean weight was 2296 g. After a fasting period of 3 h, the
      subject was fed a test meal with low and stable 13C background activity mixed
      with 50 microliters of 13C-labeled octanoic acid and 1 g polyethylene glycol
      3350. Breath samples were collected using a nasal prong in basal conditions and
      after the test meal. CO2 production according to weight and age was used in the
      calculations for 13CO2 enrichment of exhaled air. Results were expressed as
      percentage of 13C dose excretion per hour and percentage of cumulative 13C after
      4h. gastric emptying coefficient (GEC), and gastric half-emptying time (t1/2b).
      The values for percent of cumulative 13C after 4 h ranged from 30.7 to 52.6%
      (mean, 40.2%), GEC ranged from 2.7 to 3.4 (mean, 3.0), and the values for t1/2b
      ranged from 17 to 100 min (mean, 57 min). We conclude that the 13C-octanoic acid
      breath test can be adapted to preterm infants to allow the study of GE in various
      conditions.

PMID- 8856576
TI  - Facilitating effect of amino acids on fructose and sorbitol absorption in
      children.
AB  - The facilitating effect of glucose on free fructose absorption has been suggested
      to be due to a sucrase-related transport mechanism. In contrast, the conditions
      influencing the absorption of sorbitol have hardly been investigated. As amino
      acids promote transcellular water flow, we investigated their effects on the
      absorption of fructose and sorbitol. We studied 15 healthy children using breath
      hydrogen tests following the ingestion of fructose and sorbitol, alone and in
      combination with glucose or amino acids. Similarly, the effect of acarbose
      pretreatment on sucrose and fructose-glucose absorption was investigated. The
      inhibition of sucrase isomaltase by acarbose impedes the absorption of sucrose
      but not of the fructose-glucose mixture. Fructose absorption is enhanced by
      glucose and by the amino acids L-alanine, L-glutamine, L-phenylalanine, and L
      proline. Similarly, the absorption of sorbitol is facilitated by glucose and L
      alanine. These results are not in concordance with a sucrase-related fructose
      transport system and suggest another mechanism for glucose-induced enhancement of
      fructose (and sorbitol) absorption. We hypothesize that the absorption of
      fructose and sorbitol may be stimulated by the increased water flux induced by
      active absorption of glucose as well as amino acids.

PMID- 8856577
TI  - Zinc content and distribution in the newborn liver.
AB  - The newborn liver is a proven model for the study of liver storage of copper and
      iron. We analyzed zinc concentration and distribution in the livers of newborns
      and infants using a systematic tissue-sampling technique. We studied 14 newborns
      of 26-41 weeks of gestation (WG). One stillborn, and three infants (52-90 days
      old). At autopsy, a longitudinal liver slice extending from the right to the left
      lobe was subdivided into 10 samples that were analyzed for zinc concentration by
      atomic absorption spectroscopy. The mean zinc concentration in the newborn liver
      was 639 micrograms/g of dry tissue (dt). A striking interindividual variability
      in zinc liver stores was observed; the hepatic concentration of the metal ranged
      from 300 to 1,400 micrograms/g dt. We found a correlation between zinc liver
      content and gestational age. In newborns of 27-32 WG, the hepatic zinc
      concentration was significantly higher (p < 0.01) than in newborns of 34-41 WG.
      Zinc stores decreased in the postnatal period; in the infant group, the mean
      liver zinc concentration was 148 micrograms/g dt. The analysis of zinc
      concentration in 10 blocks from each liver revealed a regular distribution of the
      metal, without significant differences between liver lobes. Our data show that
      the newborn liver can be considered an interesting model for the study of zinc
      storage, which appears to correlate inversely with gestational age. From a
      practical point of view, the observed regular distribution of zinc implies that,
      at least in this model, zinc content determined in a small liver sample is
      representative of zinc content in the whole liver.

PMID- 8856578
TI  - Evaluation of bone density in newborn infants by computed x-ray densitometry.
AB  - We evaluated bone density in term and preterm infants using computed x-ray
      densitometry, which permits measurement of bone density with minimal disturbance
      to the infants in their incubators. Bone density, bone width, and bone length of
      the right radius were determined in 155 infants of appropriate weights for their
      gestational ages (23 to 41 weeks). A curve for intrauterine bone growth was
      extrapolated from these data. The mean coefficients of variations for
      variabilities for intra- and interobserver error for all measurements were <
      3.5%. In 18 infants, measurements of the right forearm were obtained in two
      positions to confirm the validity of densitometric measurements. The mean
      coefficients of variation were 3.42% for bone density, 3.48% for bone width, and
      0.21% for bone length. Bone density was significantly correlated with gestational
      age (r = 0.924) and birth weight (r = 0.921). Bone width and length were also
      correlated with gestational age (r = 0.866 and 0.937) and birth weight (r = 0.878
      and 0.954). Our results suggest that computed x-ray densitometry is a useful
      method for evaluation of bone density in preterm infants, including those in an
      intensive care environment.

PMID- 8856579
TI  - Growth hormone insensitivity in children with biliary atresia.
AB  - Malnutrition is a critical predictor of mortality and morbidity in children with
      biliary atresia who undergo orthotopic liver transplantation. Growth hormone (GH)
      enhances nitrogen retention in patients with chronic obstructive lung disease,
      sepsis, and in fasted adult volunteers. The goal of this study was to assess the
      acute response to recombinant human GH (rhGH) treatment in children with biliary
      atresia to determine whether GH therapy was likely to improve pretransplant
      nutritional status. Five children, aged 10-32 months, with biliary atresia and
      persistent cholestasis despite surgical attempts to reestablish bile flow, were
      studied. All five children had portal hypertension, conjugated
      hyperbilirubinemia, and decreased serum albumin concentrations. Length, weight,
      and growth velocity were decreased in all five children. Despite adequate energy
      and protein intake, fat stores were depleted in all five subjects, and somatic
      protein stores were diminished in all except one child. Baseline serum
      concentrations of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3
      (IGFBP-3) were low (8.4 +/- 2 ng/ml and 0.2 +/- 0.1 mg/l respectively). In the
      four children who completed the study, serum IGF-I and IGFBP-3 levels did not
      change after treatment with rhGH (0.1 mg/kg/day) for 4 days. Our findings
      indicate that children with biliary atresia awaiting liver transplantation are
      insensitive to GH and that treatment with GH is unlikely to promote anabolism. A
      rationale exists for examining the effect of treatment with IGF-I, which mediates
      the anabolic effects of GH.

PMID- 8856580
TI  - Plasma and urine riboflavin and pyridoxine concentrations in enterally fed very
      low-birth-weight neonates.
AB  - Preterm infant formulas (PIFs) for very-low-birth-weight (VLBW) infants (birth
      weight, < 1,500 g) are augmented to provide daily riboflavin and pyridoxine at
      levels up to five-fold greater than in term infant formula and 18-fold greater
      than in human milk. We evaluated plasma riboflavin and pyridoxine concentrations
      in VLBW infants who received PIF during their first postnatal month. Eighty-eight
      plasma and 124 urine samples were collected for riboflavin- and pyridoxine
      concentration measurements from 57 clinically healthy VLBW infants weekly during
      their first postnatal month. Concentrations were measured using high-performance
      liquid chromatography. At the time of the sample, patients were receiving > or =
      80% of their total calories via enteral feedings. Plasma riboflavin
      concentrations rose from 45.3 +/- 7.3 ng/ml at baseline (mean +/- SEM) to 173.5
      +/- 20.3 ng/ml by 1 week of age and remained at 177.3-199.7 ng/ml during the
      following three weekly measurements; values were up to 14-fold above baseline
      concentration. Urine riboflavin concentration increased from 534 +/- 137 ng/ml at
      baseline to 3,521 +/- 423 ng/ml by 1 week of age and remained at 4,451-5,216
      ng/ml during the next 3 weeks. In a similar pattern, baseline plasma (69.4 +/-
      10.4 ng/ml) and urine (145 +/- 30 ng/ml) pyridoxine concentrations were
      significantly increased by 1 week postnatal age; they remained at 163-248 ng/ml
      (plasma) and 1,573-2,394 ng/ml (urine) through the first postnatal month. Plasma
      and urine riboflavin and pyridoxine concentrations in enterally fed VLBW infants
      increased from baseline concentrations by 1 week of postnatal age and remained
      elevated for the first postnatal month. High daily intake and immature renal
      development are probable contributing causes of the elevated plasma riboflavin
      and pyridoxine concentrations. We suggest that lower daily enteral administration
      of riboflavin and pyridoxine should maintain adequate blood concentrations and
      minimize potential toxicity.

PMID- 8856581
TI  - Characteristics of gallbladder bile of infants and children.
AB  - In the past, biliary lipids of infants and children were studied in duodenal
      aspirates. This study was performed on original bile aspirated from the
      gallbladder. The analysis of lipids in bile demonstrated a significantly lower
      total lipid content in the bile of infants than in children (3.3 g/dl vs. 9.1
      g/dl). The most prominent difference was demonstrated in the bile salt
      concentration (43.2 mM vs. 126.7 mM) and thereafter in the phospholipid content.
      Infants had a shorter nucleation time and a higher cholesterol saturation index
      than did children. These results may explain the increased tendency of infants to
      produce sludge and gallstones during total parenteral nutrition.

PMID- 8856582
TI  - Prognostic factors in hospitalized children with persistent diarrhea:
      implications for diet therapy.
AB  - A dietary algorithm for management of persistent diarrhea in developing
      countries, using locally available foods, is yet to be standardized. We
      identified factors related to poor outcome among 75 malnourished hospitalized
      male patients aged 3-48 months with persistent diarrhea (> or = 14 days) treated
      on soy and cereal-based diet (Diet I). The 28 patients with stool output > 60 g/k
      body weight on the sixth or the seventh treatment day were considered diarrhea
      treatment failures on Diet I. In the univariate analysis, breast feeding (p <
      0.001), carbohydrate malabsorption based on low stool pH or reducing substances >
      0.5% (p = 0.03), initial 24-h purge rate (p = 0.001), pneumonia (p = 0.003), or
      probable septicemia (p = 0.03) were associated with diarrhea treatment failures.
      Although 16 of these 28 patients responded to systemic antibiotics without
      dietary modification, all but one of the remaining recovered on a chicken puree,
      glucose, and oil formulation. Twenty-six children had weight loss after 7 days on
      Diet I as compared with the postrehydration weight. These children had lower mean
      age (p = 0.05), lower food intake in the first 24 h (p = 0.05) and during the
      initial 7 days (p < 0.01), and a higher initial excretion of enteroaggregative
      Escherichia coli (32 vs. 8%; p = 0.01). In the logistic regression model,
      significant risk factors for diarrhea treatment failures were initial purge
      rates, carbohydrate malabsorption, and intercurrent systemic infection; only low
      food intake was associated with significant risk for weight loss. The significant
      association of diarrhea treatment failures with carbohydrate malabsorption
      suggests that in the initial diet itself, part of polysaccharide be substituted
      with sucrose or glucose to obtain the right balance between osmolarity and energy
      density. Our data suggest that prompt identification and treatment of systemic
      infection is critical, as its eradication achieved recovery in more than half of
      the treatment failures without a dietary change.

PMID- 8856583
TI  - Frequency and clinical pattern of celiac disease among siblings of celiac
      children.
AB  - To investigate the prevalence and clinical and genetic patterns of celiac disease
      (CD) among siblings of CD patients, 103 siblings and one twin of 80 celiac
      children were evaluated by means of their clinical history, physical examination,
      blood indices of nutritional status, and antigliadin antibodies (AGA).
      Antiendomysium antibody (AEA) levels were determined in 70 patients and 85
      subjects were human leucocyte antigen (HLA) typed. On the basis of clinical or
      laboratory data or both, 21 siblings (20.2%) were submitted to intestinal biopsy,
      whereas intestinal biopsy in six siblings with positive serologic screening (AGA
      IgA or AEA or both) was not performed because of parental refusal. In a high
      percentage of cases (18%), all on a gluten-containing diet, the intestinal mucosa
      was atrophic, and CD was subsequently diagnosed. Because we could not submit all
      the siblings to intestinal biopsy, this figure could underestimate the real
      prevalence of the disease in our series; consequently, it was not possible to
      calculate accurately the sensitivity and specificity of AGA and AEA.
      Nevertheless, AEA (positive in all the nine siblings with mucosal atrophy),
      followed by AGA IgA, proved to be the best screening for CD. Eighteen of 19 CD
      siblings showed HLA-predisposing antigens. Among the 19 CD siblings, one showed a
      typical form with gastrointestinal symptoms, two had short stature, one suffered
      from recurrent vomiting, and in 15, the disease was clinically silent. On the
      contrary, among siblings who were first diagnosed (index cases), the majority
      (73.7%) had a typical form of CD, and no clinically silent cases were observed.
      We did not find any difference between index cases and CD siblings in food habits
      and distribution of HLA antigens. In 15 of 18 cases, the sibling diagnosed
      subsequently was the older one. Finally, the typical form of CD was significantly
      more frequent among the younger brother than the older. In conclusion, the high
      prevalence of the silent form of CD in our cases indicates that siblings of CD
      subjects should always be screened for CD. The combination of AGA IgA and AEA
      represent a good screening method to use in selecting children for the intestinal
      biopsy.

PMID- 8856584
TI  - Elevation of serum interleukin-6 but not serum-soluble interleukin-2 receptor in
      children with Crohn's disease.
AB  - Previous studies have demonstrated elevated serum levels of interleukin-6 (IL-6)
      and the soluble interleukin-2 receptor (IL-2R, CD25) in individuals with
      inflammatory bowel disease (IBD). The aim of our study was to compare serum IL-6
      and IL-2R levels to see if one marker better distinguished IBD from other
      intestinal disorders or better reflected disease activity. Blood samples were
      obtained from 41 pediatric patients with Crohn's disease, 22 with ulcerative
      colitis, 19 with other gastrointestinal inflammatory disorders, and 13 with
      functional abdominal pain. Disease activity and disease location were determined
      for patients with Crohn's disease and ulcerative colitis. Serum levels of IL-6
      and IL-2R were determined by using an enzyme-linked immunosorbent assay. Mean
      serum levels of IL-6 were significantly elevated (p < 0.05) in patients with
      Crohn's disease when compared with individuals with ulcerative colitis, other
      gastrointestinal inflammatory disorders, or functional abdominal pain. By
      comparison, there was no significant difference in mean serum levels of IL-2R in
      individuals with Crohn's disease compared with these other groups. Patients with
      moderate/severe Crohn's disease had elevated mean serum levels of IL-6 and IL-2R
      when compared with those with mild and inactive disease (p < 0.05); however,
      neither marker distinguished between inactive and mild disease. IL-6 correlated
      better with the erythrocyte sedimentation rate (ESR; r = 0.57, p < 0.001) than
      did IL-2R (r = 0.28, p < 0.01). Our results suggest that elevated IL-6 levels a.e
      more likely to be seen in patients with Crohn's disease. Although IL-6 may be a
      better marker for Crohn's disease and active disease than IL-2R, it does not
      appear to offer any advantage over the ESR.

PMID- 8856586
TI  - Gastroesophageal reflux and esophagitis-associated hypertrophic osteoarthropathy.

PMID- 8856585
TI  - Management and ultrasonographic appearance of infantile hypertrophic pyloric
      stenosis with intravenous atropine sulfate.
AB  - Some infants with hypertrophic pyloric stenosis (HPS) have responded to oral
      atropine treatment. To achieve sufficient effect of atropine, it must be
      administered intravenously (i.v.). Therefore, with ultrasonography, we studied
      the changes in the pyloric muscle in HPS during and after intravenous
      administration of atropine. Twenty-three infants were studied. Atropine sulfate
      was initially administered at a dose of 0.04 mg/kg day i.v., and the dose was
      increased by 0.01 mg/kg/day until vomiting ceased. When vomiting ceased after
      administration of intravenous atropine sulfate, the infants received oral
      atropine sulfate at twice the effective intravenous dose; this was continued for
      2 weeks. Ultrasonography was repeated until pyloric muscles normalized. Twenty
      two infants were free from vomiting after 1-8 days of intravenous atropine
      sulfate (dosages of 0.04-0.11 mg/kg/day). In 21 infants, weight gain continued
      after atropine treatment even though no change in thickness of the pyloric
      muscles was demonstrated ultrasonographically. Only 2 infants required
      pyloromyotomy because of prolonged treatment or a mistake in underdosing of oral
      atropine. All of the 21 infants who recovered after intravenous atropine without
      surgery had normalization of pyloric muscle caliber, as shown by ultrasonography
      4-12 months after treatment. Atropine is an effective medicine for HPS.
      Regression of pyloric thickening after vomiting has been controlled implies that
      pyloric muscle hypertrophy could be worsened by the spasm that occurs in HPS.

PMID- 8856587
TI  - Steroid-responsive esophageal obstruction in a child with chronic granulomatous
      disease (CGD).

PMID- 8856588
TI  - Cytomegalovirus infection of the colon in ulcerative colitis: a pediatric case.

PMID- 8856589
TI  - Ciliated hepatic foregut cyst.

PMID- 8856590
TI  - Occipital cerebral calcifications and celiac disease: an additional case.

PMID- 8856591
TI  - Are multiple Broviac catheters safe in newborns? A comparison of single and
      multiple Broviac catheters.

PMID- 8856592
TI  - The infectivity of Cryptosporidium parvum in healthy volunteers.

PMID- 8856593
TI  - Dependability of esophageal pH monitoring data on software.

PMID- 8856594
TI  - Confusion surrounding nitric oxide synthase/NADPH-diaphorase.

PMID- 8856595
TI  - Burkitt-type lymphoma.

PMID- 8856596
TI  - Antidepressants a turn-off for many patients.

PMID- 8856597
TI  - Home test system for HIV approved by FDA.

PMID- 8856598
TI  - Nursing education goals changing with the times.

PMID- 8856599
TI  - The placebogenic phenomenon: art in psychiatric nursing.
AB  - 1. Nearly half of all orders for psychotropic medications are written "as needed"
      (PRN); therefore, the nurse must assume a vital function in the assessment, use,
      and evaluation of medication. 2. Placebo agents are known to have an
      effectiveness rate between 30% and 50%. Nurses and other health professionals
      severely underestimate the magnitude of this effect. 3. The patient's perception
      of the medication experience, beliefs, degree of trust, expectation, and the
      psychosocial context in which medications are used, contribute to agent
      effectiveness. 4. The nurse's personal beliefs, nonverbal cues, anticipation, and
      interpersonal style can influence effectiveness of agents in relieving symptoms;
      likewise, by understanding and increasing various interpersonal skills,
      professionals can enhance effectiveness of psychotropic agents.

PMID- 8856600
TI  - Stressors and coping strategies of homeless men.
AB  - 1 Major stressors commonly encountered by homeless men are violence to self,
      theft of belongings, inability to meet basic needs, inconsistent enforcement of
      rules by shelter staff, and other people's dehumanization or humiliation caused
      by behavior toward the men. 2 Cognitive, sociocultural, and spiritual coping
      strategies were frequently used and found to be effective in coping with
      stressors by homeless men who were either in crisis or alcohol/drug dependent. 3
      Severely and persistently mentally ill men had lower mean scores for both use and
      effectiveness of coping strategies in physical, cognitive, psychological,
      sociocultural, and spiritual strategies. 4 The longer the duration of
      homelessness, the lower the mean scores for frequency and effectiveness of use of
      coping strategies in any of the dimensions.

PMID- 8856601
TI  - Not gone and not forgotten: a spouse's experience of late-stage Alzheimer's
      disease.
AB  - 1. Late-stage caregiving is different from earlier stages, is difficult, and
      requires an empathic response from staff. 2. Ethical decision-making, supportive
      care, and the inevitability of death are important late-stage caregiver topics.
      Staff should understand the concept of palliative care. 3. Current educational
      programs and family support groups should be assessed for attention to late-stage
      caregiver issues. Further research is needed on helping families prepare for and
      cope with late stage caregiving.

PMID- 8856602
TI  - The impact of biological psychiatry on psychiatric nursing.
AB  - 1. The evidence supporting a solely biological basis for mental disorder is
      equivocal. Although any evidence may be used in support of the theory, no
      evidence is deemed sufficient to disprove it. 2. Psychiatric nursing must be
      cautious in adopting this paradigm and the view of human existence it entails,
      given the conflicting nature of the evidence, and the social, political, and
      economic forces that drive research in this field. 3. It is neither in the best
      interests of the clients we serve, nor of the profession as a whole, to surrender
      the formerly eclectic approach of nursing theory and practice in favor of a one
      dimensional model.

PMID- 8856603
TI  - Mall walking. An effective mental health intervention for older adults.
AB  - 1. Traditional goals of health promotion and disease prevention are actually
      secondary factors in many walkers' motivations for mall-walking activity. 2. The
      routine of mall walking and the social relationships they form keep older adults
      going back to the mall. 3. Successful mall-walking program directors are
      beginning to understand the need to emphasize the social benefits of
      participating in a mall-walking group as much, if not more than, the health
      benefits of regular exercise.

PMID- 8856604
TI  - Olanzapine: a new atypical antipsychotic.

PMID- 8856606
TI  - If men are really from Mars and women are really from Venus, then how are you
      changing your psychosocial care?

PMID- 8856605
TI  - Consumers as faculty: experts on their own lives.

PMID- 8856607
TI  - The antiphospholipid/cofactor syndromes.

PMID- 8856608
TI  - Synovial surfactant and the hydrophobic articular surface.

PMID- 8856609
TI  - Inflammatory polyarthritis in the community is not a benign disease: predicting
      functional disability one year after presentation.
AB  - OBJECTIVE: To predict which patients with early inflammatory polyarthritis
      presenting to primary care will be functionally disabled one year after
      presentation, in order to inform treatment and referral decisions. METHODS: The
      study population consisted of 381 patients notified to the Norfolk Arthritis
      Register, a primary care based inception cohort of patients with inflammatory
      polyarthritis. Patients were regarded as functionally disabled if they had a
      Health Assessment Questionnaire (HAQ) score of one or more. Clinical, laboratory,
      and demographic variables easily measured at baseline were analyzed for their
      ability to predict future disability. Recursive partitioning was used to create a
      simple decision tree to predict those patients who would be disabled at one year.
      A logistic regression model was generated on a sample of 277 patients and tested
      on an independent sample of 104 patients. This was compared with other models,
      one of which consisted of the 1987 ARA criteria. RESULTS: 112 (29%) patients had
      a HAQ score of at least 1 at one year. The strongest predictors of future
      disability were a high baseline HAQ, large joint involvement, female sex, and
      longer disease duration. The decision tree predicted disability accurately in 67%
      of patients. CONCLUSION: It is possible to predict functional outcome at one year
      among patients with early inflammatory polyarthritis presenting to primary care
      using simple clinical variables measured at baseline. Satisfying the 1987 ARA
      criteria could not be used to predict future disability.

PMID- 8856610
TI  - Novel mechanisms of selective apoptosis in synovial T cells of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To analyze whether T cells infiltrating the synovium of patients with
      rheumatoid arthritis (RA) express functional Fas antigen. METHODS: Mononuclear T
      cells, mainly from synovial tissues, synovial fluids (SF), and peripheral blood
      mononuclear cells (PBMC) from 14 patients with RA and 5 with osteoarthritis (OA),
      were treated with anti-Fas monoclonal antibody (Mab) (CH11) for 24 h in vitro.
      Cell viability and DNA fragmentation were examined. The expression of Fas
      antigen, Fas ligand, and T cell subpopulations was examined using flow cytometry
      and reverse transcription polymerase chain reaction. RESULTS: More than 50% of T
      cells from synovial tissue and SF of patients with RA underwent apoptosis,
      whereas no effect was observed in PBMC from RA or PBMC and synovial T cells from
      OA, suggesting that functional Fas antigens are specifically expressed on
      synovial T cells. Flow cytometric analysis demonstrated higher expression of Fas
      antigen in T cells from RA synovium than from PBMC. The T cell subpopulations
      susceptible to anti-Fas Mab were mainly CD45RO+ and CD4 or CD8 single positive T
      cells, indicating that activated mature T cells express functional Fas antigen.
      Fas ligand was overexpressed only in synovial nonadherent cells in RA at the
      level of mRNA, whereas T cells account for more than 60% of the total, but not in
      OA. CONCLUSION: These findings suggest the majority of activated T cells
      infiltrating the synovium express functional Fas antigen and Fas ligand
      specifically in patients with RA but not OA. This phenomenon may provide a clue
      to understanding the pathogenesis of RA.

PMID- 8856611
TI  - A phase I/II open label study of the safety and efficacy of an anti-ICAM-1
      (intercellular adhesion molecule-1; CD54) monoclonal antibody in early rheumatoid
      arthritis.
AB  - OBJECTIVE: Previous work suggested the potential utility of therapy with a
      monoclonal antibody (Mab) to intercellular adhesion molecule-1 (ICAM-1; CD54) in
      patients with longstanding rheumatoid arthritis (RA). Immunomodulatory
      interventions, including adhesion receptor directed therapies, might be expected
      to have greater efficacy in patients with less established or less aggressive
      disease. Therefore, we assessed the efficacy and safety of an anti-ICAM-1 Mab in
      patients with early RA. METHODS: An open label study of a 5 day infusion of an
      anti-ICAM-1 Mab in 10 patients with early or indolent RA was conducted. These
      patients were defined as having previously used < or = 1 disease modifying
      antirheumatic drug. RESULTS: Based on composite criteria, 7/10 patients had a
      marked or moderate response to therapy at one month of followup. Clinical benefit
      was sustained through 2 months for 5/10 patients and 3/10 had extended benefit
      (11, 8, and > 7 months). Clinical benefit was more likely to be obtained in
      patients with subacute onset of disease than in those with a fulminant onset.
      CONCLUSION: A single course of therapy with an anti-ICAM-1 Mab was associated
      with clinical improvement in a group of patients with early or indolent RA to an
      extent apparently greater than previously observed in patients with longstanding,
      aggressive RA.

PMID- 8856612
TI  - Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of
      rheumatoid synovial fibroblasts.
AB  - OBJECTIVE: There is evidence that proliferation of synovial fibroblasts and
      invasive growth in rheumatoid arthritis (RA) is due to impaired regulation of the
      cell cycle, i.e., the balance between proliferation and physiological cell death
      (apoptosis) We examined synovial tissues from patients with RA and osteoarthritis
      (OA) to determine the ultrastructural changes during apoptosis and the expression
      of the apoptosis regulating molecules Fas and Bcl-2 in synovial fibroblasts.
      METHODS: We examined synovial tissues obtained from patients with RA and OA by
      electron microscopy and immunoelectron microscopy to evaluate the characteristics
      of apoptosis in RA synovial fibroblasts as well as Fas and Bcl-2 antigen
      expression. RESULTS: Ultrastructurally, the majority of the RA synovial
      fibroblasts appeared transformed, and 3% of these were in different stages of
      apoptosis. In OA, no apoptotic cells could be observed. Apoptosis of synovial
      fibroblasts in RA showed a characteristic multistage pattern. In each of the
      distinguishable 4 stages, specific ultrastructural changes could be detected. The
      apoptotic synovial fibroblasts were mainly located in the deeper sublining layers
      of the synovium. Immunoelectron microscopy revealed that Fas antigen expression
      was limited to the first stage of apoptosis. Conversely, the synovial fibroblasts
      located in the synovial lining layer neither underwent apoptosis nor expressed
      Fas antigen. Several synovial lining cells expressed the cell death suppressor
      (anti-apoptosis) gene product Bcl-2. CONCLUSION: Apoptosis of fibroblasts in the
      RA synovial sublining is characterized by a distinct multistep ultrastructural
      pattern with a detectable initial Fas antigen expression; conversely, reduced
      apoptosis in the synovial lining associated with the expression of Bcl-2 results
      in extended life of matrix degrading synovial fibroblasts at the site of synovial
      invasion into cartilage and bone.

PMID- 8856613
TI  - V beta 17 T cell receptor peptide vaccination in rheumatoid arthritis: results of
      phase I dose escalation study.
AB  - OBJECTIVE: To determine whether modulation of activated T cells occurs in
      patients with rheumatoid arthritis (RA) after immunization with T cell receptor
      (TCR) V beta 17 peptides, a phase I trial was initiated to investigate the safety
      and feasibility of TCR peptide immunization as a therapeutic approach in RA.
      METHODS: 15 patients with moderate to severe RA were given an intramuscular
      injection of one of 4 doses (10, 30, 100, and 300 micrograms) of the V beta 17
      peptide vaccination, followed by a booster injection of the same dose of vaccine
      3 weeks later. Patients were followed for 48 weeks. RESULTS: The product was well
      tolerated and no serious adverse events attributable to the vaccine were
      observed. This was an uncontrolled phase I trial, however; decreases in patients
      joint scores were observed at all followup visits starting at 4 weeks after
      primary immunization. Activated V beta 17 T cells (IL-2R+) in peripheral blood
      were decreased (> or = 20%) in 3/5 patients in the 100 micrograms group after
      initial measurement at Week 2 and 3/4 patients in the 300 micrograms group 3
      weeks after immunization. Lymphocyte proliferation in response to the V beta 17
      peptide was detected at 6 weeks or later after primary inoculation in 6/15
      patients (40%) immunized. CONCLUSION: Further controlled studies are required to
      assess the biologic and clinical efficacy of this treatment approach.

PMID- 8856614
TI  - HLA-DRB1 and DQB typing of Hispanic American patients with rheumatoid arthritis:
      the "shared epitope" hypothesis may not apply.
AB  - OBJECTIVE: To determine whether the association of particular MHC class II
      alleles and the DRB1 "shared epitope" with disease susceptibility and severity in
      rheumatoid arthritis (RA) applies to ethnic groups other than Caucasian
      Americans. METHODS: 67 Hispanic American patients with RA and a similar number of
      ethnically matched controls were typed for DRB1 using polymerase chain reaction
      methods. DR4 subtype and DQB1 type were determined for the subjects positive for
      DR4. Disease severity in the patients with RA was assessed by clinical,
      radiographic and laboratory variables. RESULTS: The frequency of DR4 was
      significantly increased in the subjects with RA compared to the control group.
      However, the "shared" DRB1 amino acid sequence was relatively infrequent in the
      Hispanic American patients with RA, and there was no association of specific DR4
      or DQ alleles with more severe disease or extraarticular manifestations.
      CONCLUSION: The HLA markers that predict poor prognosis and suggest that more
      aggressive clinical management may be appropriate in Caucasian American patients
      with RA may not be useful in other ethnic groups.

PMID- 8856615
TI  - Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies.
      I. Association with thrombosis and vascular cutaneous diseases.
AB  - OBJECTIVE: To detect antiphosphatidylethanolamine antibodies (aPE) as the only
      antiphospholipid antibodies (aPL) in 122 patients we investigated for aPL and to
      correlate the presence of aPL with clinical manifestations. METHODS: Patients
      with autoimmune diseases (n = 41), thromboembolic episodes (TEE) (n = 34), livedo
      reticularis (LR) without (n = 17) or with (n = 14) thrombosis or recurrent fetal
      losses (RFL), systemic vasculitides (n = 10), and miscellaneous disorders (n = 6)
      were investigated for antibodies directed against 4 anionic phospholipids (PL)
      (cardiolipin, phosphatidylserine, inositol, phosphatidic acid) and lupus
      anticoagulant (LAC) and then for aPE by modified ELISA. RESULTS: 15 patients had
      aPE and no antibodies to anionic PL including LAC. 7 had IgM, 4 had IgG plus IgM,
      and 4 had IgG. These aPE were significantly more often associated with TEE alone,
      with TEE and LR, or with LR alone (p = 0.004) than with autoimmune diseases.
      CONCLUSION: The detection of aPE as the sole aPL in one patient with mesenteric
      infarcts and RFL led to the diagnosis of primary antiphospholipid syndrome.
      Followup of 3 patients showed that aPE cannot be considered as transient
      autoantibodies. Therefore, patients whose clinical symptoms suggest
      antiphospholipid syndrome but whose sera are negative for antibodies to
      cardiolipin or another anionic PL should be screened for aPE, particularly
      patients with thrombosis, RFL, and/or LR.

PMID- 8856616
TI  - Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies
      detected by ELISA. II. Kininogen reactivity.
AB  - OBJECTIVE: To study the requirement for serum and for low (LMWK) and high
      molecular weight kininogen (HMWK) and/or HMWK binding proteins to detect
      antiphosphatidylethanolamine antibodies (aPE) in ELISA. METHODS: Eighteen
      patients with aPE (9 IgG and 13 IgM) as the only antiphospholipid antibody (aPL)
      detected by ELISA were assigned to 4 groups: thromboembolic episodes (TEE) (Group
      I, n = 6); livedo reticularis (LR) without TEE, (Group II, n = 4); both LR and
      thrombosis (Group III, n = 4); and systemic lupus erythematosus (SLE) or primary
      antiphospholipid syndrome (APS) (Group IV, n = 4). All sera were analyzed in
      ELISA with and without bovine serum and with a purified chromatographic fraction
      containing LMWK, HMWK, and HMWK binding proteins. RESULTS: Eleven aPE were serum
      dependent: mostly IgG (7/9) and some IgM (4/13). Among the 11 serum dependent
      aPE, all the 7 IgG and 2 IgM were kininogen reactive. Some serum independent IgM
      were better detected in the absence than in the presence of serum in the ELISA.
      CONCLUSION: In the 18 patients, kininogens and/or HMWK binding proteins served as
      a "cofactor" significantly more often for aPE IgG than for aPE IgM (p = 0.007).
      Kininogen dependent aPE Ig were observed more often in patients with LR with or
      without TEE (6/8) than in those with SLE or primary APS (0/4) but this difference
      merely tended to significance (p = 0.06). In 2 patients, one with TEE, the other
      with primary APS, the IgM aPE was dependent on a serum "cofactor" that was not
      kininogen.

PMID- 8856617
TI  - A functional index in myositis.
AB  - OBJECTIVE: To evaluate the interrater reliability and the construct validity of a
      specially constructed functional index and to assess functional status in 23
      patients with myositis; and to describe the occurrence, intensity, and
      distribution of pain in these patients. METHODS: The functional test scored
      muscle endurance in extremities, neck, and trunk, grip strength, peak expiratory
      flow, turning in bed, and transferring from lying in bed to sitting. The scores
      of the different functions were added to create a functional index. The patients'
      subjective gradings of disability and pain intensity were indicated on a category
      scale. Blood samples for analyses of muscle enzyme levels were obtained in
      connection with the functional tests. RESULTS: The interrater reliability of the
      functional index was high. Grip strength and muscle endurance in shoulder
      abduction and flexion, hip flexion, and a step test and heel and toe lifting were
      significantly reduced compared to controls. Peak expiratory flow was lowered in 4
      patients. The functional index did not correlate significantly with the
      laboratory tests, but there was significant correlation between the weakness of
      the lower extremities and the subjective grading of disability. All patients but
      one had experienced severe pain during the course of the disease. CONCLUSION: The
      described functional index has high interrater reliability, but its construct
      validity and sensitivity as a monitor of response to medication and training need
      further confirmation.

PMID- 8856618
TI  - Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac
      sodium in patients with knee osteoarthritis.
AB  - OBJECTIVE: To assess the clinical efficacy of chondroitin sulfate (CS) in
      comparison with the nonsteroidal antiinflammatory drug (NSAID) diclofenac sodium
      (DS) in a medium/longterm clinical study in patients with knee osteoarthritis
      (OA). METHODS: This was a randomized, multicenter, double blind, double dummy
      study. 146 patients with knee OA were recruited into 2 groups. During the first
      month, patients in the NSAID group were treated with 3 x 50 mg DS tablets/day and
      3 x 400 mg placebo (for CS) sachets; from Month 2 to Month 3, patients were given
      placebo sachets alone. In the CS group, patients were treated with 3 x 50 mg
      placebo (for diclofenac) tablets/day and 3 x 400 mg CS sachets/day during the
      first month; from Month 2 to Month 3, these patients received only CS sachets.
      Both groups were treated with 3 x 400 mg placebo sachets from Month 4 to Month 6.
      Clinical efficacy was evaluated by assessing the Lequesne Index, spontaneous pain
      (using the Huskisson visual analog scale), pain on load (using a 4 point ordinal
      scale), and paracetamol consumption. RESULTS: Patients treated with the NSAID
      showed prompt and plain reduction of clinical symptoms, which, however,
      reappeared after the end of treatment; in the CS group, the therapeutic response
      appeared later in time but lasted for up to 3 months after the end of treatment.
      CONCLUSION: CS seems to have slow but gradually increasing clinical activity in
      OA; these benefits last for a long period after the end of treatment.

PMID- 8856619
TI  - Clinical and neurocognitive features of the post Lyme syndrome.
AB  - OBJECTIVE: To evaluate neurocognitive impairment in patients with persistent
      arthralgia, fatigue, and subjective memory loss in patients after Lyme disease
      (post-Lyme syndrome, PLS). METHODS: We compared the clinical, neurocognitive, and
      psychological features of 23 patients with PLS to 23 age, sex, and education
      matched recovered patients (REC). All met Centers for Disease Control criteria
      for Lyme disease, were ELISA positive at onset of Lyme disease and were
      previously treated with standard antibiotic regimens. RESULTS: Of the patients
      with PLS, 7 (30%) had fibromyalgia (FM), 3 (13%) had chronic fatigue syndrome,
      and 10 (43%) had similar but milder symptoms but did not meet the criteria for
      either. 22 of 23 patients with PLS complained of decreased memory or
      concentration problems. Patients with PLS had significantly lower scores on the
      attention/concentration scale (p = 0.012) of the Wechsler Memory Scale-Revised
      (WMS-R), indicating lowered attention/concentration. 52% of patients with PLS and
      35% in the REC group had significantly lower (p < 0.05) WMS-R verbal memory
      scores than visual memory scores. The PLS group had subjectively more problems
      with sleep and mood changes and higher scores on several scales of Symptom Check
      List 90-R (p < 0.01), indicating greater physical distress. Beck Depression
      Inventory scores were also higher for the PLS than the REC group (p < 0.005), but
      were within the normal range. CONCLUSION: Despite antibiotic treatment, a
      sequelae of Lyme disease may be a PLS characterized by persistent arthralgia,
      fatigue, and neurocognitive impairment that is probably induced by Lyme disease.

PMID- 8856620
TI  - Altered dermatan sulfate proteoglycan synthesis in fibroblast cultures
      established from skin of patients with systemic sclerosis.
AB  - OBJECTIVE: To study whether changes in the properties of skin from patients with
      systemic sclerosis (SSc) are the result of altered metabolism of dermatan sulfate
      proteoglycans. METHODS: Fibroblast cultures were established from skin of healthy
      controls, and from affected and unaffected skin of patients with SSc. Synthesized
      proteoglycans were labeled with 3H glucosamine and 35S sulfate. The amount of
      mRNA of the different dermatan sulfate proteoglycans was determined by
      hybridization with the corresponding cDNA probes. RESULTS: A 2-fold increase in
      secretion of total proteoglycans was found in cell cultures from affected and
      normal appearing skin from patients with SSc. The production of 2 different
      dermatan sulfate proteoglycans was increased. Aggrecan/versican increased 4-fold
      and decorin 2-fold in cultures of affected skin from patients with SSc. The mRNA
      for decorin increased 3-fold, while the mRNA level for versican increased only
      slightly. Similar but less marked changes were noted in cultures from normal
      appearing skin. In contrast, the biglycan mRNA level decreased and the product
      could only be found in very small amounts in SSc cultures. CONCLUSION: This
      marked alteration of dermatan sulfate proteoglycan metabolism distinguishes not
      only affected skin but also normal appearing SSc skin from that of controls. The
      altered proteoglycan production may affect organization of matrix fibers and
      thereby the fibrotic process observed in patients with SSc.

PMID- 8856621
TI  - The prevalence and meaning of fatigue in rheumatic disease.
AB  - OBJECTIVE: To determine the prevalence of fatigue in rheumatic disease; to
      characterize the strength of associations between demographic and clinical
      features and fatigue; to identify predictors of fatigue, and to determine the
      consequence of clinically significant fatigue. METHODS: 1488 consecutive patients
      with rheumatic disease were assessed with the Clinical Health Assessment
      Questionnaire, a health status instrument with scales for fatigue, pain, global
      severity, sleep disturbance, gastrointestinal problems, anxiety, depression,
      health status, health satisfaction, and work ability. All patients underwent
      rheumatic disease examinations and laboratory testing. RESULTS: Fatigue measured
      by visual analog scale (VAS) was present in 88-98% of patients, but clinically
      important levels of fatigue (> or = 2.0 on VAS) were present in more than 41% of
      patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and 76% of those
      with fibromyalgia (FM). Fatigue was related to almost all demographic and
      clinical variables, but in multivariate analyses the strongest independent
      predictors of fatigue were pain, sleep disturbance, depression, tender point
      count and Health Assessment Questionnaire (HAQ) disability. About 90% of the R2
      of the model (all patients = 0.51, RA = 0.49, OA = 0.45, FM = 0.41) was explained
      by pain, sleep disturbance, and depression. In RA assessed by erythrocyte
      sedimentation rate, joint count and grip strength, no association of the
      inflammatory process with fatigue could be found in the multivariate analyses. In
      measuring health status, fatigue was strongly associated with work dysfunction
      and general measures of health (VAS of global severity, health status, and health
      satisfaction). CONCLUSION: Fatigue is common across all rheumatic diseases,
      associates with all measures of distress, and is a predictor of work dysfunction
      and overall health status. The correlates of fatigue are generally similar across
      RA, OA and FM. Fatigue assessment adds much to understanding and management of
      patients and diseases.

PMID- 8856622
TI  - Pathogenetic aspects of responsiveness to ondansetron (5-hydroxytryptamine type 3
      receptor antagonist) in patients with primary fibromyalgia syndrome--a
      preliminary study.
AB  - OBJECTIVE: To study the efficacy of 5-hydroxytryptamine type 3 receptor (5-HT-3R)
      antagonist (ondansetron) vs paracetamol in primary fibromyalgia (FM) syndrome.
      METHODS: A double blind, crossover, latin square study of 21 patients with FM.
      Visual analog scale (VAS) and body drawings were used to record pain intensity.
      Functional symptoms were determined for using a Likert-type self-developed
      protocol. Quantitative dolorimetry was applied to assess the number of painful
      tender points and the average pain threshold. Serum serotonin levels were
      measured by a commercial ELISA. RESULTS: A marked improvement in pain intensity
      measured by VAS (p < 0.005), pain score (p < 0.05), tender points (p < 0.05), and
      average pain threshold (p < 0.01) was obtained with ondansetron, whereas no
      improvement was seen with paracetamol. After ondansetron treatment, there was
      also significant reduction in both functional symptoms (p < 0.01) and headache
      intensity (p < 0.05). In patients who did not respond to ondansetron there was
      higher baseline pain intensity measured by VAS (p < 0.05) and pain score (p <
      0.01), and a lower pain threshold (p < 0.05) compared to those who did respond
      well. In the responsive group, no significant differences were seen in the
      serotonin level before and after therapy. Whereas a significant increase in serum
      serotonin concentration (p < 0.01) was observed in nonresponders after
      ondansetron treatment. CONCLUSION: Ondansetron appears to be an effective drug in
      about 50% of patients with FM. There may be 2 subsets of patients with FM that
      differ clinically and pathogenetically with regard to the disturbance in the 5-HT
      3R system.

PMID- 8856623
TI  - Cyclosporin a therapy in refractory juvenile dermatomyositis. Experience and
      longterm followup of 6 cases.
AB  - OBJECTIVE: Cyclosporin A (CyA) has been reported to be an effective treatment of
      adult polymyositis (PM) and dermatomyositis (DM) refractory to corticosteroid
      therapy. We aimed to determine the effectiveness of CyA in the treatment of
      juvenile dermatomyositis (JDM) refractory to corticosteroids and cytotoxic
      agents. METHODS: Retrospective study of 6 patients with refractory JDM based on
      medical charts. RESULTS: Better clinical control of the disease was obtained in
      all cases and corticosteroid doses could be markedly decreased or stopped. 4
      patients relapsed, 3 after discontinuation of CyA, but recovered after its
      reinitiation. Trough CyA levels were maintained between 51 and 247 ng/ml, and
      side effects were rare and minor during a mean followup of 51.5 months.
      CONCLUSION: CyA seems to be an effective treatment of JDM and should be
      considered in case of severe or refractory disease.

PMID- 8856624
TI  - Cerebral infarction and antiphospholipid syndrome in children.
AB  - OBJECTIVE: To investigate the prevalence of antiphospholipid antibodies (aPL) in
      children with acute cerebral infarction. METHODS: The study was carried out in 10
      consecutive patients during the first days of neurological symptoms. aPL detected
      as lupus anticoagulant or anticardiolipin antibodies (aCL) and natural
      anticoagulant proteins C, S, and antithrombin III were determined in all
      patients. RESULTS: Seven patients had acute cerebral infarctions associated with
      aCL; 4 of these patients had high serum aCL concentrations in 2 different
      determinations (antiphospholipid syndrome). Two patients had temporary protein C
      deficiency. In one patient with negative aCL, protein C, S, and antithrombin III
      determinations were not carried out. No patient had evidence of connective tissue
      disease or family history of hypercoagulable state. After followup of 15.7
      months, no patient had recurrent infarction while taking aspirin. CONCLUSION: Our
      study demonstrates high prevalence of aCL in children who suffer acute cerebral
      infarction and our results suggest aspirin may be effective therapy to prevent
      recurrences.

PMID- 8856625
TI  - Synovial cyst as differential diagnosis of supraclavicular mass in rheumatoid
      arthritis.
AB  - We describe a mass located at the supraclavicular space in a patient with a 5
      year history of erosive rheumatoid arthritis. The mass was initially diagnosed as
      a suspected metastasis, but direct puncture and magnetic resonance imaging
      revealed a cyst. Clinical and radiological characteristics are described and
      pathogenesis and treatment are discussed.

PMID- 8856626
TI  - Graves' disease associated with the primary antiphospholipid syndrome.
AB  - We describe a patient in whom highly active Graves' disease occurred in close
      temportal relationship with extensive, recurrent, venous thrombosis due to
      primary antiphospholipid syndrome. (J. Rheumatol 1996;23:1435-7).

PMID- 8856627
TI  - Synovial cyst at the C1-C2 junction and spondyloarthropathy.
AB  - A spinal synovial cyst is a rare extradural benign tumor generally located at the
      lumbar spine, arising at the facet joint capsule, and usually associated with
      degenerative changes. We describe a 64-year-old woman with a synovial cyst
      involving the quadrate ligament of the odontoid process, which caused neurologic
      signs. Her family history was positive for spondyloarthropathy. The radiologic
      investigations, preoperative differential diagnosis, and association of
      spondyloarthropathy with this rare benign foramen magnum tumor are of particular
      interest.

PMID- 8856628
TI  - Anterior atlantoaxial subluxation in a patient with diffuse idiopathic skeletal
      hyperostosis.
AB  - We describe an 80-year-old woman with neck pain that radiated to the back and
      left side of her head. Radiographs of the cervical spine showed calcification and
      ossification of the anterior longitudinal ligament of the spine from the C3 to
      the C7 level, erosive destruction of the lateral masses of the atlas and axis,
      and anterior atlantoaxial subluxation (AAS). Diffuse idiopathic skeletal
      hyperostosis (DISH) was diagnosed. This is to the best of our knowledge the first
      reported case of DISH accompanied by AAS.

PMID- 8856629
TI  - Cervical spine pseudogout with myelopathy and Charcot joints.
AB  - Myelopathy due to calcium pyrophosphate dihydrate (CPPD) crystals in the cervical
      spine is rare. Neuropathic-like joints are also uncommon manifestations of CPPD
      crystal disease. We describe a 79-year-old woman with multiple neuropathic joints
      containing CPPD crystals. She also had a large mass containing CPPD crystals
      impinging on the cervical spinal cord, causing a myelopathy. She appears to be
      the first patient with this combination of unusual clinical features with CPPD
      disease.

PMID- 8856630
TI  - Inguinal lymph node foreign body granulomas after placement of a silicone rubber
      (Silflex) implant of the first metatarsophalangeal joint.
AB  - We describe a woman who developed foreign body granulomas 8 years after
      metatarsophalangeal (MTP) joint silicone rubber implantation for hallux rigidus.
      She developed overnight swelling and tenderness in the inguinal region on the
      ipsilateral side. Histological evaluation of the lymph node showed foreign body
      granulomas. Electron microscopy and dispersion x-ray analysis identified the
      foreign body material in the inguinal lymph node and fibrous capsule surrounding
      the implant as silicone. Foreign body granulomas of surrounding tissues and
      regional lymph nodes are infrequently reported postoperative complications in
      patients with small joint silicone rubber implants. A fractured or eroded implant
      surface attributed to wear is usually noted at prosthesis excision. Granulomas in
      normal or enlarged lymph nodes have been described in both symptomatic and
      asymptomatic patients, with intact or fractured prostheses. Many related joint
      and lymph node symptoms resolve with removal of the silicone rubber prosthesis.

PMID- 8856631
TI  - Hemochromatosis-like arthropathy in diabetes mellitus without hemochromatosis.
AB  - We describe 3 patients with non-insulin-dependent diabetes mellitus who presented
      with hand pain and swollen joints. All 3 had radiographic changes in the affected
      joints typical of those associated with hemochromatosis. None of these patients
      had hemochromatosis. This is the first description of hemochromatosis-like
      arthropathy in diabetes mellitus without hemochromatosis.

PMID- 8856632
TI  - The Dunlop-Dottridge Memorial Lecture. Paleopathology as a clinical science with
      implications for patient care, education, and research.

PMID- 8856633
TI  - Soluble interleukin 2 receptors and treatment with hydroxychloroquine in erosive
      osteoarthritis.

PMID- 8856634
TI  - Lipoprotein(a) and anticardiolipin antibodies as risk factors for thrombotic
      events in polymyalgia rheumatica and giant cell arteritis.

PMID- 8856635
TI  - Systemic lupus erythematosus and pheochromocytoma.

PMID- 8856636
TI  - Arthritis after bacillus Calmette-Guerin therapy.

PMID- 8856637
TI  - SAPHO syndrome and pulmonary disease.

PMID- 8856638
TI  - Hyperprolactinemia preceding development of autoimmune disease.

PMID- 8856639
TI  - Excess risk of lung cancer in patients with rheumatoid arthritis.

PMID- 8856640
TI  - Reactive arthritis associated with bacillus Calmette-Guerin immunotherapy for
      carcinoma of the bladder: immune reactivity against mycobacterial antigens.

PMID- 8856641
TI  - Cardiac valve disease in Wegener's granulomatosis.

PMID- 8856642
TI  - Acanthosis nigricans associated with longstanding dermatomyositis.

PMID- 8856643
TI  - The epidemiology of osteoporosis.
AB  - Osteoporosis is defined as "...a systemic skeletal disease characterized by low
      bone mass and microarchitectural deterioration of bone tissue, with a consequent
      increase in bone fragility and susceptibility to fracture." Compared to normal
      bone, osteoporotic bone shows a reduction in the number of trabeculae, thinning
      of the trabeculae, and loss of connectivity of the trabeculae. The overall result
      is deterioration of bone strength and an increase in the susceptibility to
      fracture. Osteoporosis is essentially a "silent" disease until a fracture occurs.
      When multiple fractures occur, they can cause significant deformity of the spine,
      leading to kyphosis, loss of vertebral height, and subsequent loss of overall
      height. The patient with osteoporosis experiences chronic pain and back fatigue.
      In addition, gastrointestinal and respiratory symptoms may occur as a consequence
      of the changes in the skeletal shape.

PMID- 8856644
TI  - Mechanisms of bone loss.
AB  - We have seen rapid and important advances in the understanding of bone resorption
      processes at the cellular and molecular levels. Indeed, the field of molecular
      and cellular biology of bone is proliferating at a virtually exponential rate.
      Osteoclastic bone resorption, the major process involved in Type 1 osteoporosis,
      is the target of several pharmacological agents for the treatment of
      osteoporosis, and is the potential target of several agents that are proposed for
      the treatment of osteoporosis. This review will focus on (1) the factors known or
      postulated to affect bone loss; (2) the function of the differentiated osteoclast
      and the pharmacological effects on osteoclast function; (3) the processes
      involved in the generation and differentiation of mature osteoclasts and, again,
      the pharmacological implications of these processes.

PMID- 8856645
TI  - Current treatment options for osteoporosis.
AB  - The goals of treatment for patients with osteoporosis are to maintain normal bone
      and to prevent the deterioration of normal bone to osteoporotic bone. Achievement
      of these goals, combined with a successful approach to prevention of falls, may
      substantially decrease the incidence and risk of fractures. Strategies for
      osteoporosis therapy include patient strategies (e.g., administration of calcium,
      exercise), drug therapy to stimulate bone formation (e.g., fluoride, anabolic
      steroids), and drugs to inhibit bone resorption (e.g., estrogen replacement
      therapy, calcitonin, bisphosphonates).

PMID- 8856646
TI  - The role of vitamin D in the pathogenesis and treatment of osteoporosis.
AB  - It is well recognized that patients with postmenopausal osteoporosis usually
      exhibit some degree of calcium malabsorption and commonly have low serum
      concentrations of 1,25-dihydroxyvitamin D (calcitriol). Administration of
      calcitriol has been shown to normalize calcium absorption in patients with
      osteoporosis and, over the long term may have a stimulating effect on bone
      formation. Clinical trials have shown a significant reduction in osteoporotic
      fractures among calcitriol-treated patients. Hypercalcemia and hypercalciuria are
      infrequent complications of calcitriol therapy with physiologic doses (0.25
      microgram twice daily), and are most commonly related to excessive calcium intake
      (i.e., > 1000 mg daily).

PMID- 8856647
TI  - Corticosteroid induced osteoporosis.
AB  - In contrast to most other forms of osteoporosis, the major clinical manifestation
      of corticosteroid induced osteoporosis, in terms of fracture, is at the spine
      and, to a lesser extent, the ribs. Accordingly, the most important consideration
      in the selection of therapy for corticosteroid induced osteoporosis is the effect
      of particular agents on spine bone mineral density. Calcitriol (the active
      hormonal from of vitamin D) and the bisphosphonates appear to be effective agents
      in the treatment of corticosteroid induced spinal bone loss.

PMID- 8856648
TI  - Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits
      and neuronal damage after global ischemia in rats.
AB  - Glutamate antagonists have been shown to be neuroprotective in animal models of
      cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal
      damage in the hippocampus and striatum. Following ischemia a deficit in spatial
      learning and memory occurs. The aim of the present study was to investigate the
      potential neuroprotective effect of GYKI 52466, an antagonist at the non-N-methyl
      D-aspartate receptor, with behavioural and histological measures of global
      ischemia in rats. Global ischemia was induced by four-vessel-occlusion (4VO) for
      20 min in rats. GYKI 52466 (30 mg/kg i.p.) was administered either 20 min before
      induction of ischemia or immediately after onset of reperfusion. One week after
      surgery spatial learning was tested in the Morris water maze. After behavioural
      testing the animals were sacrificed and the neuronal damaged was assessed. GYKI
      52466 reduced the increase in escape latency and in swim distance induced by 4VO
      when given before ischemia but not when applied after ischemia. Neuronal damage
      in the CA1 sector of the hippocampus produced by 4VO was significantly attenuated
      by pretreatment but not by posttreatment with GYKI 52466. Striatal neuronal
      damage was not affected by either treatment with GYKI 52466. GYKI 52466 had
      neuroprotective effects in a rat model of global cerebral ischemia. Pretreatment
      with GYKI 52466 protected rats against behavioural deficits and hippocampal
      neuronal damage induced by 4VO.

PMID- 8856649
TI  - Delayed intravenous administration of basic fibroblast growth factor (bFGF)
      reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the
      rat.
AB  - Basic fibroblast growth factor (bFGF) is a potent neurotrophic and vasoactive
      peptide. Previous studies have shown that intraventricularly-administered bFGF
      reduces the size of cerebral infarcts following focal ischemia. In the current
      study, we tested the effects of intravenously-administered bFGF in a model of
      focal ischemia/reperfusion. The right middle cerebral artery of mature male
      Wistar rats was occluded by intraluminal suture. After 2 h of occlusion, the
      suture was removed and intravenous infusion of bFGF in vehicle (45
      micrograms/kg/h) or vehicle alone was begun, lasting 3 h. Animals were weighed
      and evaluated neurologically until sacrifice 7 days after ischemia. The volume of
      cerebral infarcts was then determined by H and E staining and image analysis. We
      found a 40% reduction in infarct volume in bFGF- vs. vehicle-treated rats (n = 11
      vs. 11, P < 0.05). Reduction in infarct volume was associated with improved
      neurological outcome and regained body weight in bFGF-treated animals (both P <
      0.05). No change in blood pressure was found during bFGF treatment. These results
      show that the delayed intravenous administration of bFGF reduces infarct size in
      this model of focal ischemia/reperfusion. The mechanisms of infarct reduction may
      include direct cytoprotective and/or vasoactive effects.

PMID- 8856650
TI  - Extraocular, limb and diaphragm muscle group-specific antioxidant enzyme activity
      patterns in control and mdx mice.
AB  - The mechanisms primarily responsible for the degenerative processes occurring in
      dystrophic skeletal muscle remain unresolved. The identification of the
      mechanisms that lead to the complete sparing of extraocular muscle in
      dystrophinopathies is of particular interest. A number of studies have provided
      evidence to suggest that the muscle pathology that characterizes muscular
      dystrophy may be, in part, free radical mediated. In the present study, we
      examined the antioxidant enzyme status of extraocular, diaphragm and
      gastrocnemius muscles in control strain and mdx mice. Our results revealed that
      in the control strain, both extraocular and diaphragm muscles had higher
      copper/zinc superoxide dismutase, manganese superoxide dismutase and selenium
      dependent glutathione peroxidase activities as compared to the gastrocnemius.
      Furthermore, the diaphragm had higher glutathione reductase activity as compared
      to the gastrocnemius. These findings indicate that the highly aerobic extraocular
      and diaphragm muscles have higher antioxidant enzyme capacity than the
      gastrocnemius, a muscle more dependent on anaerobic energy metabolism. Changes in
      the antioxidant enzyme status of the mdx mouse correlated, in part, with the
      degree of histopathological involvement of the three muscle groups assessed.

PMID- 8856651
TI  - Hereditary neuropathy with liability to pressure palsies: distinguishing clinical
      and electrophysiological features among patients with multiple entrapment
      neuropathy.
AB  - Hereditary neuropathy with liability to pressure palsies is caused by deletion of
      the PMP-22 gene. As its relatively mild symptoms may escape detection by clinical
      examination alone, we screened the gene in patients with multiple entrapment
      neuropathy (MEN) that had been diagnosed by nerve conduction studies (NCS). Two
      of the eight patients with MEN had deletion of the gene. The characteristic
      features that distinguished them from the other MEN patients were predominantly
      sensory deficits associated with mild weakness and subclinical polyneuropathy as
      detected by NCS.

PMID- 8856652
TI  - Sporadic early adult-onset distal myopathy with rimmed vacuoles:
      immunohistochemistry and electron microscopy.
AB  - We report the histoenzymology, immunohistochemistry and electron microscopy of
      the tibialis anterior muscle of a 50-year-old male patient affected by a sporadic
      distal myopathy with onset during adolescence. There was no family history of
      muscle disorder and no clinical signs of cardiomyopathy. Extremely large
      variations in muscle fibre diameter (the size of some fibres exceeding 200-250
      microns), rimmed vacuoles, necrotic fibres invaded by macrophages, atrophic
      fibres and perimysial fibrosis were observed. Using a wide range of antibodies
      raised against membrane- and cytoskeletal muscle proteins, granular desmin
      immunoreactivity was observed in muscle fibre lesions. There were no inflammatory
      parameters. Of special interest was the occurrence of autophagic vacuoles without
      18-20 nm thick sarcoplasmic filaments and the presence of small aggregates of
      intermediate desmin-like filaments among a great diversity of ultrastructural
      findings. The morphological differential diagnosis is discussed. Our results
      stress the importance of combined immunohistochemistry and electron microscopy in
      the delineation of distal myopathies. DNA defects, however, still have to be
      identified which would improve the present classifications of distal myopathies.

PMID- 8856653
TI  - The cortical representation of somatosensory evoked potentials of the phrenic
      nerve.
AB  - Respiratory electrophysiological studies are of essential value in diagnosing and
      managing patients with respiratory failure, but assessment of the sensory phrenic
      nerve fibres has been neglected. We recorded phrenic nerve somatosensory evoked
      potentials (SSEPs) by combining neurophysiological and neuroimaging techniques in
      three healthy subjects. Evoked potentials of the phrenic nerve showed the highest
      amplitude at CP3, determined by the modified 10-20 EEG system, and occurred at a
      constant latency, PI at 12.0 +/- 0.6 ms, and NI at 17.3 +/- 0.8 ms. Single photon
      emission computer tomography (SPECT) performed during phrenic nerve stimulation
      revealed focal neuronal activation in the somatosensory pathways. Intravenously
      administered Tc-99m Ethyl Cysteinate Dimer (ECD) was used as a blood flow tracer
      to obtain baseline and activated images. After image registration, baseline
      images were compared voxel-by-voxel with the activation images. The mean inter
      subject summation image of the activated state was compared with that of the
      baseline state using ten normal subjects. The extent of the total voxel volume
      increase on the mean images of the 3 activated SPECT images was 0.7%, and a mean
      signal increase of 22%. For further anatomic localization of regional increases
      in signal, the magnetic resonance image (MRI) scan of each subject was registered
      and superimposed on the activated stage SPECT image. This method may be used
      clinically to study the pathophysiology of impaired central respiratory drive.

PMID- 8856654
TI  - Tenascin in denervated human muscle.
AB  - Tenascin is a large oligomeric glycoprotein of the extracellular matrix. Its
      location is innervated muscle tissues. We investigated immunohistologically,
      using two monoclonal antibodies (mah) against Tenascin, biopsied denervated human
      muscle of children and adults. Tenascin was present in the interstitial space
      among denervated muscle fibres. Accumulation of Tenascin in denervated adult
      muscle tissue was frequent, accumulation in denervated muscle tissue of children
      was sparse and weak. The two antibodies reacted correspondingly. Tenascin was not
      only found in the vicinity of atrophic muscle fibres, but also close to normally
      sized fibres, suggesting an early stage of denervation even before reduction of
      muscle fibre volume.

PMID- 8856655
TI  - PET study of cerebral glucose metabolism and fluorodopa uptake in patients with
      corticobasal degeneration.
AB  - We measured cerebral glucose utilization and fluorodopa metabolism in the brain
      of patients with corticobasal degeneration using position emission tomography.
      The clinical pictures are distinctive, comprising features referable to both
      cerebral cortical and basal ganglionic dysfunctions. Brain images of glucose
      metabolism can demonstrate specific abnormalities with a marked asymmetry in the
      parietal cortex (the primary motor and sensory cortex and the lateral parietal
      cortex), the thalamus, the caudate nucleus and the putamen of the dominantly
      affected hemisphere related to clinical symptoms in six patients. [18F]dopa
      uptake also reduced in an asymmetric pattern, both the caudate nucleus and the
      putamen in four patients. This unique combination study measuring both cerebral
      glucose utilization and fluorodopa metabolism in the nigrostriatal system can
      provide efficient information about the dysfunctions which are correlated with
      individual clinical symptoms.

PMID- 8856656
TI  - Motor skill learning in Parkinson's disease.
AB  - The motor performance of patients with Parkinson's disease is degraded, but it is
      unclear whether their motor learning (adaptation learning and skill learning)
      ability is impaired. To assess the ability of these patients to learn motor
      tasks, we studied nine Parkinson's disease patients and eight age-matched normal
      (control) subjects who repetitively traced, as rapidly and accurately as
      possible, irregular geometric patterns with normal and mirror-reversed vision.
      The outcome was measured by statistical analysis and graphic plotting of values
      for actual and standardized performance variables and correlation of data from
      initial and final performance variables with indicators of disease severity. The
      results showed that, with normal vision, total movement time was reduced in both
      patients and normal subjects, but movement errors increased with repetition,
      apparently reflecting a speed-accuracy trade-off and adaptation learning. With
      mirror-reversed vision, total movement time and movement errors were reduced
      equally with repetition in both groups. These concomitant improvements in time
      and accuracy violate the rule of speed-accuracy trade-off and suggest that this
      behavior reflects true motor skill learning. We conclude that patients with
      Parkinson's disease do not differ from normal subjects in the processes of motor
      adaptation and motor skill learning.

PMID- 8856657
TI  - Subacute sclerosing panencephalitis (SSPE): early diagnosis, prognostic factors
      and natural history.
AB  - We studied the value of long video-split electroencephalographic monitoring
      (VSEEG) in detecting myoclonus in nearly SSPE and evaluated the natural history
      and outcome-affecting factors. The 32 newly diagnosed patients had VSEEG to
      detect myoclonus and its correlations with EEG periodic complexes. Disease
      progression was monitored by a special "outcome score'; the chi-square test and
      multi-variable statistics analysed the outcome score in relation to different
      variables, such as age at onset, sex, duration of symptoms at presentation, CSF
      measles antibody titre, type and interval between periodic complexes (EEG
      discharges). Myoclonus or atonia occurred in all patients and was time-related to
      the EEG periodic complexes; in 32% of patients, myoclonus or atonia were not
      clinically evident. The EEG periodic complexes were of 3 types: Type I (16
      patients) periodic giant delta waves; Type II (10 patients) periodic giant delta
      waves intermixed with rapid spikes or fast activity; and Type III (6 patients),
      long spike-wave discharges interrupted by giant delta waves. Outcome score was
      associated with symptoms duration (P < 0.01) and EEG periodic complexes (P <
      0.05). Symptom duration was inversely related to final outcome (multi-variable
      analysis). Long VSEEG monitoring greatly improves early diagnosis and detection
      of subtle atonia or segmental myoclonus. Prognostic factors were the type of EEG
      periodic complexes and duration of symptoms at presentation.

PMID- 8856658
TI  - Recurrent demyelinating transverse myelitis in a high titer HBs-antigen carrier.
AB  - A 46-year-old man who was an extremely high titer hepatitis B surface (HBs)
      antigen carrier had three attacks of acute demyelinating transverse myelitis
      associated with signs of meningeal irritation. Each episode showed good response
      to corticosteroid therapy. The cerebrospinal fluid was characterized by elevated
      levels of myelin basic protein (MBP) and predominating CD4+CD29+ helper-inducer T
      cells during the acute stages, and also by persistently positive HBs antigen.
      There were neither autoantibodies nor evidence of vasculitis. However,
      circulating immune complexes composed of HBs antigen disappeared after treatment,
      indicating that immunity to hepatitis B virus played a role in the demyelinative
      lesion formation in the central nervous system (CNS). In light of the animal
      studies demonstrating autoimmunity triggered by molecular mimicry between MBP and
      hepatitis B virus antigens, this patient may serve as a rare example of CNS
      demyelination in humans with the same autoimmune etiology.

PMID- 8856659
TI  - Analysis of ballistic movements in ataxic hemiparesis following a pontine stroke.
AB  - Although cerebellar-like ataxia is a well known component of the ataxic
      hemiparesis (AH), the mechanism of hypermetria in AH has not been established. We
      describe a patient presenting a left AH following a right pontine infarction. We
      investigated the ballistic flexion movements of both wrists and the associated
      agonist and antagonist electromyographic (EMG) activities, before and after
      addition of inertial loads. At the time of motion analysis, neurological
      examination showed cerebellar-like dysmetria of the left side but the patient had
      recovered a normal strength. In the basal state (without addition of loads),
      movements of the left wrist were hypermetric. The duration of the agonist EMG
      activity was prolonged and the onset latency of the antagonist EMG activity was
      not delayed. Moreover, when a mass was added, the hypermetria was unchanged
      because the patient was unable to adapt appropriately neither the agonist, nor
      the antagonist EMG activity. We suggest that the hypermetria was due to an
      imbalance between the duration of the agonist EMG activity (the launching force)
      and the duration of the antagonist EMG activity (the braking force).

PMID- 8856660
TI  - Yes/yes head tremor without appendicular tremor after bilateral cerebellar
      infarction.
AB  - We report a 67-year-old man who developed yes/yes head tremor without
      appendicular tremor six weeks after right occipital and bilateral cerebellar
      infarction. The tremor was resting-postural. Its activity increased with
      excitement, decreased either after ethanol, lateroflexion or rest and stopped at
      sleep. Four-vessel angiography revealed a well collateralised occlusion of both
      vertebral arteries. Needle-EMG recordings showed rhythmic, synchronous
      agonist/antagonist activity in both the splenius capitis and
      sternocleidomastoideus muscles at a frequency of 2-3 Hz. After administration of
      botulinum toxin A (DysportR), the tremor markedly improved and vanished
      completely after a booster. Since then the tremor did not reappear. Delayed
      onset, yes/yes head tremor without appendicular tremor may be caused by bilateral
      cerebellar infarction and can be successfully relieved with botulinum toxin A.

PMID- 8856661
TI  - Phytol metabolites are circulating dietary factors that activate the nuclear
      receptor RXR.
AB  - RXR is a nuclear receptor that plays a central role in cell signaling by pairing
      with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was
      defined as a potent RXR activator. Here we describe a unique RXR effector
      identified from organic extracts of bovine serum by following RXR-dependent
      transcriptional activity. Structural analyses of material in active fractions
      pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent
      transcription at concentrations between 4 and 64 microM. Although 200 times more
      potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract
      and cannot be present at a concentration that could account for the activity.
      Phytanic acid, another phytol metabolite, was synthesized and stimulated RXR with
      a potency and efficacy similar to phytanic acid. These metabolites specifically
      displaced [3H]-9cRA from RXR with Ki values of 4 microM, indicating that their
      transcriptional effects are mediated by direct receptor interactions. Phytol
      metabolites are compelling candidates for physiological effectors, because their
      RXR binding affinities and activation potencies match their micromolar
      circulating concentrations. Given their exclusive dietary origin, these
      chlorophyll metabolites may represent essential nutrients that coordinate
      cellular metabolism through RXR-dependent signaling pathways.

PMID- 8856662
TI  - Functionally distinct isoforms of dynactin are expressed in human neurons.
AB  - P150Glued is the largest subunit of dynactin, which binds to cytoplasmic dynein
      and activates vesicle transport along microtubules. We have isolated human cDNAs
      encoding p150Glued as well as a 135-kDa isoform; these isoforms are expressed in
      human brain by alternative mRNA splicing of the human DCTN1 gene. The p135
      isoform lacks the consensus microtubule-binding motif shared by members of the
      p150Glued/Glued/CLIP-170/BIK1 family of microtubule-associated proteins and,
      therefore, is predicted not to bind directly to microtubules. We used transient
      transfection assays and in vitro microtubule-binding assays to demonstrate that
      the p150 isoform binds to microtubules, but the p135 isoform does not. However,
      both isoforms bind to cytoplasmic dynein, and both partition similarly into
      cytosolic and membrane cellular fractions. Sequential immunoprecipitations with
      an isoform-specific antibody for p150 followed by a pan-isoform antibody revealed
      that, in brain, these polypeptides assemble to form distinct complexes, each of
      which sediments at approximately 20 S. On the basis of these observations, we
      hypothesize that there is a conserved neuronal function for a distinct form of
      the dynactin complex that cannot bind directly to cellular microtubules.

PMID- 8856663
TI  - Talin requires beta-integrin, but not vinculin, for its assembly into focal
      adhesion-like structures in the nematode Caenorhabditis elegans.
AB  - In cultured cells, the 230-kDa protein talin is found at discrete plasma membrane
      foci known as focal adhesions, sites that anchor the intracellular actin
      cytoskeleton to the extracellular matrix. The regulated assembly of focal
      adhesions influences the direction of cell migrations or the reorientation of
      cell shapes. Biochemical studies of talin have shown that it binds to the
      proteins integrin, vinculin, and actin in vitro. To understand the function of
      talin in vivo and to correlate its in vitro and in vivo biochemical properties,
      various genetic approaches have been adopted. With the intention of using
      genetics in the study of talin, we identified a homologue to mouse talin in a
      genetic model system, the nematode Caenorhabditis elegans. C. elegans talin is
      39% identical and 59% similar to mouse talin. In wild-type adult C. elegans,
      talin colocalizes with integrin, vinculin, and alpha-actinin in the focal
      adhesion-like structures found in the body-wall muscle. By examining the
      organization of talin in two different C. elegans mutant strains that do not make
      either beta-integrin or vinculin, we were able to determine that talin does not
      require vinculin for its initial organization at the membrane, but that it
      depends critically on the presence of integrin for its initial assembly at
      membrane foci.

PMID- 8856664
TI  - Abnormal kinetochore structure activates the spindle assembly checkpoint in
      budding yeast.
AB  - Saccharomyces cerevisiae cells containing one or more abnormal kinetochores delay
      anaphase entry. The delay can be produced by using centromere DNA mutations
      present in single-copy or kinetochore protein mutations. This observation is
      strikingly similar to the preanaphase delay or arrest exhibited in animal cells
      that experience spontaneous or induced failures in bipolar attachment of one or
      more chromosomes and may reveal the existence of a conserved surveillance pathway
      that monitors the state of chromosome attachment to the spindle before anaphase.
      We find that three genes (MAD2, BUB1, and BUB2) that are required for the spindle
      assembly checkpoint in budding yeast (defined by antimicrotubule drug-induced
      arrest or delay) are also required in the establishment and/or maintenance of
      kinetochore-induced delays. This was tested in strains in which the delays were
      generated by limited function of a mutant kinetochore protein (ctf13-30) or by
      the presence of a single-copy centromere DNA mutation (CDEII delta 31). Whereas
      the MAD2 and BUB1 genes were absolutely required for delay, loss of BUB2 function
      resulted in a partial delay defect, and we suggest that BUB2 is required for
      delay maintenance. The inability of mad2-1 and bub1 delta mutants to execute
      kinetochore-induced delay is correlated with striking increases in chromosome
      missegregation, indicating that the delay does indeed have a role in chromosome
      transmission fidelity. Our results also indicated that the yeast RAD9 gene,
      necessary for DNA damage-induced arrest, had no role in the kinetochore-induced
      delays. We conclude that abnormal kinetochore structures induce preanaphase delay
      by activating the same functions that have defined the spindle assembly
      checkpoint in budding yeast.

PMID- 8856666
TI  - Activation-induced subcellular redistribution of Gs alpha.
AB  - We have examined the subcellular distribution of alpha s, the alpha subunit of
      the heterotrimeric G protein Gs, by using immunofluorescence microscopy. In
      transiently transfected HEK293 cells, wild-type alpha s localizes to the plasma
      membrane. However, a mutationally activated alpha s (alpha sR201C) is diffusely
      distributed throughout the cytoplasm. Similarly, cholera toxin activation of
      alpha s causes it to redistribute from the plasma membrane to cytoplasm in stably
      transfected cells. In HEK293 cells stably transfected with alpha s and the beta 2
      adrenergic receptor (beta-AR), stimulation of the beta-AR by the agonist
      isoproterenol also causes a translocation of alpha s from the plasma membrane to
      cytoplasm. Replacing the agonist with antagonist allows alpha s to return to the
      plasma membrane, demonstrating the reversibility of alpha s translocation.
      Receptor-activated alpha s does not colocalize with internalized beta-AR at
      endosomes. Incubation of cells in hypertonic sucrose to inhibit clathrin-coated
      pit-mediated endocytosis of agonist-activated beta-AR failed to block agonist
      stimulated redistribution of alpha s. These findings demonstrate that activated
      alpha s reversibly undergoes a translocation from the plasma membrane to
      cytoplasm and begin to address the relationship between regulated trafficking of
      a seven-transmembrane receptor and its cognate G protein.

PMID- 8856665
TI  - Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases
      cell motility and proliferation.
AB  - It has been proposed that the focal adhesion kinase (FAK) mediates focal adhesion
      formation through tyrosine phosphorylation during cell adhesion. We investigated
      the role of FAK in focal adhesion structure and function. Loading cells with a
      glutathione-S-transferase fusion protein (GST-Cterm) containing the FAK focal
      adhesion targeting sequence, but not the kinase domain, decreased the association
      of endogenous FAK with focal adhesions. This displacement of endogenous FAK in
      both BALB/c 3T3 cells and human umbilical vein endothelial cells loaded with GST
      Cterm decreased focal adhesion phosphotyrosine content. Neither cell type,
      however, exhibited a reduction in focal adhesions after GST-Cterm loading. These
      results indicate that FAK mediates adhesion-associated tyrosine phosphorylation,
      but not the formation of focal adhesions. We then examined the effect of
      inhibiting FAK function on other adhesion-dependent cell behavior. Cells
      microinjected with GST-Cterm exhibited decreased migration. In addition, cells
      injected with GST-Cterm had decreased DNA synthesis compared with control
      injected or noninjected cells. These findings suggest that FAK functions in the
      regulation of cell migration and cell proliferation.

PMID- 8856667
TI  - A sex recognition glycoprotein is encoded by the plus mating-type gene fus1 of
      Chlamydomonas reinhardtii.
AB  - Sexual fusion between plus and minus gametes of the unicellular green alga
      Chlamydomonas reinhardtii entails adhesion between plus-specific and minus
      specific "fringe" proteins displayed on the plasma membrane of gametic mating
      structures. We report the identification of the gene (fus1) encoding the plus
      fringe glycoprotein, which resides in a unique domain of the mating-type plus
      (mt+) locus, and which was identified by transposon insertions in three fusion
      defective mutant strains. Transformation with fus1+ restores fringe and fusion
      competence to these mutants and to the pseudo-plus mutant imp11 mt-, defective in
      minus differentiation. The fus1 gene is remarkable in lacking the codon bias
      found in all other nuclear genes of C. reinhardtii.

PMID- 8856668
TI  - Methylation of high molecular weight fibroblast growth factor-2 determines post
      translational increases in molecular weight and affects its intracellular
      distribution.
AB  - The high molecular weight (HMW) forms (24, 22.5, and 22 kDa) of basic fibroblast
      growth factor-2 (FGF-2) contain an N-terminal extension responsible for their
      predominantly nuclear localization. These forms of FGF-2 are post-translationally
      modified, resulting in a 1- to 2-kDa increase in apparent molecular mass. Here we
      show that this post-translational modification is inhibited by methionine
      starvation and by the methyltransferase inhibitors 5'-deoxy-5'
      methylthioadenosine (MTA) and 3-deaza-adenosine. Inhibition of the methylation
      dependent modification results in a significant decrease in HMW FGF-2 nuclear
      accumulation, suggesting that methylation is relevant to the intracellular
      distribution of these forms of FGF-2. Treatment with MTA does not affect either
      the synthesis or the intracellular fate of another nuclear protein, the SV40
      large T antigen, demonstrating that this drug does not have a generalized effect
      on nuclear protein accumulation. These results link HMW FGF-2 post-translational
      modification to its intracellular distribution.

PMID- 8856669
TI  - Myosin II transport, organization, and phosphorylation: evidence for cortical
      flow/solation-contraction coupling during cytokinesis and cell locomotion.
AB  - The mechanism of cytokinesis has been difficult to define because of the short
      duration and the temporal-spatial dynamics involved in the formation, activation,
      force production, and disappearance of the cleavage furrow. We have investigated
      the structural and chemical dynamics of myosin II in living Swiss 3T3 cells from
      prometaphase through the separation and migration of daughter cells. The
      structural and chemical dynamics of myosin II have been defined using the
      semiautomated, multimode light microscope, together with a fluorescent analogue
      of myosin II and a fluorescent biosensor of myosin II regulatory light chain
      (RLC) phosphorylation at serine 19. The correlation of image data from live cells
      using different modes of light microscopy allowed interpretations not possible
      from single-mode investigations. Myosin II transported toward the equatorial
      plane from adjacent regions, forming three-dimensional fibers that spanned the
      volume of the equator during anaphase and telophase. A global phosphorylation of
      myosin II at serine 19 of the RLC was initiated at anaphase when cortical myosin
      II transport started. The phosphorylation of myosin II remained high near the
      equatorial plane through telophase and into cytokinesis, whereas the
      phosphorylation of myosin II at serine 19 of the RLC decreased at the poles. The
      timing and pattern of phosphorylation was the same as the shortening of myosin II
      based fibers in the cleavage furrow. Myosin II-based fibers shortened and
      transported out of the cleavage furrow into the tails of the two daughter cells
      late in cytokinesis. The patterns of myosin II transport, phosphorylation, and
      shortening of fibers in the migrating daughter cells were similar to that
      previously defined for cells migrating in a wound in vitro. The temporal-spatial
      patterns and dynamics of myosin II transport, phosphorylation at serine 19 of the
      RLC, and the shortening and disappearance of myosin II-based fibers support the
      proposal that a combination of the cortical flow hypothesis and the solation
      contraction coupling hypothesis explain key aspects of cytokinesis and polarized
      cell locomotion.

PMID- 8856670
TI  - The G alpha i homologue gna-1 controls multiple differentiation pathways in
      Neurospora crassa.
AB  - Heterotrimeric G proteins are components of principal signaling pathways in
      eukaryotes. In higher organisms, alpha subunits of G proteins have been divided
      into four families, Gi, Gs, Gq, and G12. We previously identified a G alpha i
      homologue gna-1 in the filamentous fungus Neurospora crassa. Now we report that
      deletion of gna-1 leads to multiple phenotypes during the vegetative and sexual
      cycles in N. crassa. On solid medium, delta gna-1 strains have a slower rate of
      hyphal apical extension than wild type, a rate that is more pronounced under
      hyperosmotic conditions or in the presence of a cellophane overlay. delta gna-1
      mutants accumulate less mass than wild-type strains, and their mass accumulation
      is not affected in the same way by exposure to light. delta gna-1 strains are
      defective in macroconidiation, possessing aerial hyphae that are shorter, contain
      abnormal swellings, and differentiate adherent macroconidia. During the sexual
      cycle, delta gna-1 strains are fertile as males. However, the mutants are female
      sterile, producing small, aberrant female reproductive structures. After
      fertilization, delta gna-1 female structures do not enlarge and develop normally,
      and no sexual spores are produced. Thus, mutation of gna-1 results in sex
      specific loss of fertility.

PMID- 8856672
TI  - Organization of face representation in the cingulate cortex of the rhesus monkey.
AB  - Neuroanatomical and electrophysiological methods were used to investigate the
      organization of face representation in the cingulate gyrus of four rhesus
      monkeys. Injections of fluorescent tracers placed into electrophysiologically
      defined sectors of the primary (M1) and supplementary (M2) motor cortices
      demonstrated that the rostral part of area 24c and the rostral part of area 23c
      send projections to the face representations of M1 and M2. Injections of
      biotinylated dextran amine involving the rostral part of area 24c and rostral
      part of area 23c demonstrated a direct projection from both areas to the facial
      nucleus of the pons. Our data suggest that areas 24c (M3) and 23c (M4) each
      contain a face representation which directly affects cortical as well as
      subcortical neural centers controlling facial activity.

PMID- 8856673
TI  - Gene expression of angiotensin II receptor subtypes in the cerebellar cortex of
      young rats.
AB  - Both AT1 and AT2 receptors were detected in the cerebellar cortex of 2-week-old
      rats by [125I]Sar1-angiotensin II binding. In contrast, using in situ
      hybridization histochemistry we found only AT1A and AT1B but not AT2 receptor
      mRNA in the cerebellar cortex of young rats. Expression of AT1A and AT1B receptor
      mRNA coding for either receptor subtype was found in the molecular or granular
      cell layers. Our results suggest that AT1 receptors may be located on dendrites
      of Purkinje cells expressing AT1A and AT1B receptor mRNA, whereas the AT2
      receptor binding in the molecular layer may be located on nerve terminals of
      fibers projecting to the cerebellar, cortex from distant areas.

PMID- 8856671
TI  - Nuclear accumulation of fibroblast growth factor receptors is regulated by
      multiple signals in adrenal medullary cells.
AB  - In an effort to determine the localization of fibroblast growth factor (FGF)
      receptors (FGFR) that could mediate the intracellular action of FGF-2, we
      discovered the presence of high-affinity. FGF-2 binding sites in the nuclei of
      bovine adrenal medullary cells (BAMC). Western blot analysis demonstrated the
      presence of 103-, 118-, and 145-kDa forms of FGFR1 in nuclei isolated from BAMC.
      125I-FGF-2 cross-linking to nuclear extracts followed by FGFR1
      immunoprecipitation showed that FGFR1 can account for the nuclear FGF-2 binding
      sites. Nuclear FGFR1 has kinase activity and undergoes autophosphorylation.
      Immunocytochemistry with the use of confocal and electron microscopes
      demonstrated the presence of FGFR1 within the nuclear interior. Nuclear
      subfractionation followed by Western blot or immunoelectron microscopic analysis
      showed that the nuclear FGFR1 is contained in the nuclear matrix and the
      nucleoplasm. Agents that induce translocation of endogenous FGF-2 to the nucleus
      (forskolin, carbachol, or angiotensin II) increased the intranuclear accumulation
      of FGFR1. This accumulation was accompanied by an overall increase in FGF-2
      inducible tyrosine kinase activity. Our findings suggest a novel mode for growth
      factor action whereby growth factor receptors translocate to the nucleus in
      parallel with their ligand and act as direct mediators of nuclear responses to
      cell stimulation.

PMID- 8856674
TI  - Decreased neurofilament gene expression is an index of selective axonal
      hypotrophy in ageing.
AB  - Axonal atrophy may reflect earlier and more reversible events in
      neurodegeneration and ageing than somatic atrophy. Innervation density by
      sympathetic fibres from the rat superior cervical ganglion (SCG) to the middle
      cerebral artery (MCA) decreases dramatically in old age, while that to the iris
      is largely unchanged. In situ hybridization was used in conjunction with
      retrograde tracers to examine the role of the neuronal cytoskeleton in this
      selective axonal vulnerability. Using a riboprobe complementary to neurofilament
      light chain (NF-L) mRNA, there was a 22-25% decrease in the mean grain density in
      aged neurones when all neurones were examined. A small subset of these neurones
      was shown to project to the MCA and another to the iris. In young SCG, both
      subpopulations expressed intermediate grain densities for NF-L mRNA. In MCA
      projecting neurones, there was a 40% decline in grain density with ageing (p <
      0.05), with no change in iris-projecting neurones. Our results demonstrate that
      major decreases in NF-L expression may represent cellular markers of selective
      axonal hypotrophy by aged neurones.

PMID- 8856675
TI  - Neglect for low luminance contrast stimuli but not for high colour contrast
      stimuli: a behavioural and electrophysiological case study.
AB  - We describe a patient with a right hemisphere lesion involving the frontal lobe,
      the post-central gyrus and the superior parietal lobule. Behavioural testing
      demonstrated severe left unilateral neglect to low luminance contrast stimuli,
      but not to high colour contrast stimuli. Evoked potentials to low contrast
      luminance gratings presented in the left hemifield were not reliable. However,
      equiluminant coloured gratings presented in the same hemifield evoked reliable
      electrophysiological responses, although longer in latency than those evoked in
      the right hemifield. These findings suggest that the patient has severe damage of
      the high contrast sensitivity magnocellular pathway in the right hemisphere, with
      minor involvement of the parvocellular pathway.

PMID- 8856676
TI  - Alzheimer's disease affects parallel processing between the auditory cortices.
AB  - Auditory evoked magnetic fields (AEFs) were recorded from 11 patients with
      Alzheimer's disease (AD) and 11 age-matched controls using the 122-channel whole
      head magnetometer. Auditory stimuli were monaurally presented with interstimulus
      intervals (ISI) of 0.5 and 2.5 s in different blocks. The peak latencies of P50m
      and N100m responses were significantly longer in AD patients than in controls
      over the ipsilateral but not over the contralateral auditory cortex with respect
      to the ear stimulated. This finding suggests that parallel auditory processing is
      impaired between the auditory cortices in AD patients. The present MEG
      measurement might provide an objective index to evaluate auditory dysfunction in
      AD.

PMID- 8856677
TI  - Orphanin FQ/nociceptin-immunoreactive nerve fibers parallel those containing
      endogenous opioids in rat spinal cord.
AB  - Antisera were developed that specifically recognize orphanin FQ/nociceptin, the
      17 amino acid peptide reported to be the endogenous ligand for the orphan opioid
      receptor. Immunocytochemical localizations in rat spinal cord demonstrated that
      orphanin FQ /nociceptin-immunoreactivity (-ir) was abundant in superficial dorsal
      horn, lateral spinal nucleus and the region dorsal to the central canal, areas
      that also exhibit prominent enkephalin-and dynorphin-ir. Orphanin FQ/nociceptin
      ir was not affected by dorsal rhizotomy, indicating that in spinal cord the
      peptide is produced by central rather than primary afferent neurons. thus, the
      distribution of orphanin FQ/nociceptin-ir appeared in neuronal circuits that
      parallel those containing enkephalin- and dynorphin-ir, with only modest co
      existence of these peptides.

PMID- 8856678
TI  - Tyrosine hydroxylase-immunoreactive cells in the nodose ganglion for the canine
      larynx.
AB  - Several substances have been reported as candidates for the neurotransmitter in
      the laryngeal afferent system. In the present study we demonstrated that
      catecholamine is also a candidate neurotransmitter in the canine laryngeal
      afferent system using tyrosine hydroxylase (TH) immunochemistry in combination
      with retrograde labelling with cholera toxin B in subunit-conjugated gold (CTBG).
      A few cells in the nodose ganglion labelled by application of CTBG to the
      internal branch of the superior laryngeal nerve were also TH-immunoreactive.
      These cells were also labelled following application of CTBG to the nucleus of
      the solitary tract. These results indicate that some of the TH-IR cells in the
      nodose ganglion could be primary afferent neurones for the canine larynx.

PMID- 8856679
TI  - Abundance of the longer A beta 42 in neocortical and cerebrovascular amyloid beta
      deposits in Swedish familial Alzheimer's disease and Down's syndrome.
AB  - Recent studies have demonstrated the deposition of amyloid beta (A beta) protein
      with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular
      deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific
      antibodies to A beta peptides, we examined the immunocytochemical distribution of
      A beta 40 and A beta 42 species in brain tissue from a Swedish subject with
      familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid
      beta precursor protein (A beta PP), and from subjects with Down's syndrome and
      sporadic AD. In the Swedish subject, we found profound parenchymal A beta
      deposits and cerebral amyloid angiopathy in all four cortical lobes and
      cerebellum. A beta 42 was evident in almost all parenchymal deposits as well as
      many vascular deposits. Although A beta 40 was present in meningeal and
      intraparenchymal vessels, deposits containing this shorter peptide reactivity
      were sparse. Surprisingly, our observations in Swedish FAD showing a remarkable
      abundance of A beta 42 in both parenchymal and vascular deposits were
      qualitatively similar to the Down's syndrome and most sporadic AD cases, and to
      previously published A beta PP717 FAD. While previous transfection studies in
      different cell cultures indicate substantially increased soluble A beta
      production and A beta 40 species to be predominant, it would appear that the
      double A beta PP mutations in Swedish FAD largely result in the deposition of the
      longer A beta 42 in vivo.

PMID- 8856680
TI  - A novel antioxidant alleviates heat hyperalgesia in rats with an experimental
      painful peripheral neuropathy.
AB  - Rats with an experimental painful peripheral neuropathy (the chronic injury (CCI)
      model) display heatevoked hyperalgesia. There is now considerable evidence that
      nitric oxide (NO) and nitric oxide synthase are involved in the development of
      hyperalgesia in acute inflammatory pain states. The mechanisms responsible for
      hyperalgesia in chronic pain state may involve not only NO itself, but also
      peroxynitrite, the product of its reaction with superoxide radical, .O2- that can
      lead to the formation of the free radicals .OH and NO2- Under normal metabolic
      conditions, the cellular enzyme super oxide dismutase (SOD) provides
      physiological defence against superoxide radicals. TEMPOL mimics SOD and acts as
      a catalyst to remove the .O2- radical. The present work shows the efficacy of a
      stable nitroxide radical, 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-1-oxyl
      (TEMPOL), against heat-evoked hyperalgesia.

PMID- 8856681
TI  - Injured nerve block alters adjacent nerves spinal interaction in neuropathic
      rats.
AB  - Baseline activity and responses to simultaneous saphenous stimulation of pairs of
      neurones recorded from sciatic (L5-6) and saphenous (L2) spinal cord segments, in
      rats with thermal hyperalgesia following sciatic constriction, were analysed
      before, during and after a sciatic nerve block with a local anaesthetic. In
      sciatic neurones, during the block, reductions of baseline activity (p < 0.001),
      increases in threshold of saphenous electrical stimulation (p < 0.01) and
      reductions of responses to electrical and to natural noxious saphenous stimuli (p
      < 0.001) were consistently found. The neuronal baseline and evoked activities
      remained unmodified in saphenous neurones. The contribution of input from injured
      periphery to central neurone circuitry mechanisms underlying the unmasking of
      improper afferents is discussed.

PMID- 8856682
TI  - Persisting versus sustained neural activity: effects on transient N100m response.
AB  - Previous evidence from animal and human studies suggests that neural activity,
      both during a continuous tone and persisting after the offset of a first tone,
      can prolong the latency and enhance the amplitude of a transient response to a
      second tone. Our results showed that the latency of N100m to a second tone
      presented to the opposite ear was prolonged equally in both conditions.
      Unexpectedly, the effects on response strength strongly depended on stimulus
      laterality: the ipsilateral but not the contralateral N100m to the second tone
      was enhanced by the simultaneous presence of the first when compared with the
      effect of the preceding tone. This suggests that sustained neural activity during
      a continuous tone can release inhibition normally induced by ipsilateral
      stimulation.

PMID- 8856683
TI  - Increased density of I2-imidazoline receptors in human glioblastomas.
AB  - A glial location has been proposed for the non-adrenoceptor [3H]idazoxan binding
      site termed the I2-imidazoline receptor. The specific binding of [3H]idazoxan in
      the presence of (-)adrenaline was measured in membranes from excised human
      glioblastomas (n = 6), meningiomas (n = 6) and normal brains (n = 6). The
      pharmacological profile of the [3H]idazoxan binding in astrocytic tumours was
      similar to that in normal brain, compatible with the presence of I2-imidazoline
      receptors. There was a higher density of I2-imidazoline receptors in astrocytic
      tumours (Bmax = 266 +/- 18 fmol mg-1 protein; p < 0.001) than in normal brain
      (Bmax = 54 +/- 4 fmol mg-1 protein), with no differences in affinity values.
      Almost no [3H]idazoxan-specific binding was shown in meningiomas. The results
      suggest that I2-imidazoline receptors may be a selective marker for glial tumours
      in the evaluation of intracranial neoplasms.

PMID- 8856684
TI  - Inhibition of N-acetylaspartate production: implications for 1H MRS studies in
      vivo.
AB  - The effect of specific irreversible inhibitors of complexes I, III, IV and V of
      the mitochondrial respiratory chain, (rotenone, myxothiazol, cyanide and
      oligomycin, respectively) on mitochondrial N-acetylaspartate production, and its
      relationship to oxidative phosphorylation (ATP production and oxygen consumption)
      were investigated in isolated rat brain mitochondria. Mitochondrial N
      acetylaspartate production, ATP production and oxygen consumption were all
      significantly decreased in the presence of each of the inhibitors used compared
      with control incubations, and correlated positively with each other. It is
      postulated that decreased N-acetylaspartate levels seen in disease states by 1H
      NMR spectroscopy in vivo may reflect primarily an impaired mitochondrial energy
      production rather than neuronal cell loss.

PMID- 8856685
TI  - Carbachol mimics effects of sensory input on tyrosine phosphorylation in cortex.
AB  - We have recently shown that in the gustatory cortex of the rat, taste learning
      enhances protein tyrosine phosphorylation and taste memory is blocked by
      muscarinic antagonists. A major protein whose tyrosine phosphorylation is
      stimulated by taste learning in cortex is a 180 kDa synaptic glycoprotein
      identified as the NMDA receptor subunit 2B (NR2B). Here we report that
      microinjection of carbachol into the taste cortex modulates protein tyrosine
      phosphorylation similarly to the effect of unfamiliar taste, and that a 180 kDa
      protein whose tyrosine phosphorylation is enhanced in vivo by carbachol is NR2B.
      These data, combined with our previous findings, are in line with the hypothesis
      that muscarinic input plays a role in encoding new items in memory, and that
      tyrosine phosphorylation of NR2B is involved in this process.

PMID- 8856686
TI  - High-affinity binding of [3H]paroxetine to caudate nucleus and microvessels from
      porcine brain.
AB  - Serotonin (5-HT) is an important signal molecule not only for neurones but also
      for a variety of other cell types. Targeting the brain endothelium, the
      constitutive element of the blood-brain barrier (BBB), it elicits permeability
      changes. Using the selective 5-HT uptake inhibitor [3H]paroxetine we demonstrated
      the presence of a 5-HT transporter-like protein at the BBB. The binding
      capacities (Bmax) at the BBB (382 fmol mg-1) and on caudate nucleus membranes
      (392 fmol mg-1) were similar. However, the binding affinities differed by a
      factor of 5 (membranes: Kd = 0.10 nM, BBB: 0.47 nM). The affinities of various
      specific uptake inhibitors were also 2- to 13-fold lower in the microvessel
      preparation. It is suggested that the 5-HT transporter(s) in the brain and
      microvessels are different or differently regulated proteins.

PMID- 8856687
TI  - Altered responsiveness of medullary depressor neurones to L-glutamate and D
      serine in SHR rats.
AB  - We have investigated the effects of microinjection of L-glutamate, D-serine and
      glycine into the caudal ventrolateral medulla (CVLM) of spontaneously
      hypertensive (SHR) and Wistar Kyoto (WKY) rats. In SHR the depressor responses to
      L-glutamate were significantly enhanced compared to WKY rats, while those to the
      NMDA-glycine site agonists, D-serine and glycine (in the presence of strychnine)
      were significantly diminished. Depressor responses to NMDA and D-serine could be
      blocked with 5-fluro-indole-2-carboxylic acid (FICA, an NMDA-glycine site
      antagonist). In support of our previous findings, the larger responses of NMDA
      glutamate site agonists and smaller responses of NMDA-glycine site agonists in
      SHR, may suggest that SHR have reduced levels of the endogenous glutamate
      antagonist, kynurenic acid.

PMID- 8856688
TI  - A null mutation allele in the CNTF gene and schizophrenic psychoses.
AB  - The maldevelopmental theory postulates disturbances in neural development as
      crucial factors in the aetiopathogenesis of schizophrenia. Neurotrophic factors,
      including ciliary neurotrophic factor (CNTF), play a central role in the
      regulation of such development. A mutation has been described for the CNTF gene,
      whereby subjects homozygous for the mutation lack CNTF. The polymerase chain
      reaction was used to amplify the CNTF gene region containing this mutation in
      whole blood genomic DNA. The mutation was detected by analysis of restriction
      fragment length polymorphisms. Patients suffering from schizophrenic psychosis
      (ICD-10 criteria) (51 from Wurzburg, 83 from Barcelona), and healthy controls (62
      from Wurzburg, 50 from Barcelona) were investigated. In the Wurzburg group, the
      frequency of subjects homozygous or heterozygous for the mutation was
      significantly higher among schizophrenic patients than in controls. However, no
      difference could be detected in the Spanish sample; the possible reasons for the
      different allele distribution in the two patient groups is discussed. It is
      concluded that the CNTF null mutation may be relevant to the aetiopathogenesis of
      schizophrenia in some patients, but further work is required to identify
      specifically the patient group for which it is important.

PMID- 8856689
TI  - Intact spatial learning following lesions of basal forebrain cholinergic neurons.
AB  - The role of the basal forebrain cholinergic system in learning and memory has
      held considerable interest since the discovery of cholinergic neurodegeneration
      in the basal forebrain in Alzheimer's disease. Contrary to expectation, selective
      removal of basal forebrain cholinergic neurons projecting to either hippocampus
      or neocortex fails to impair learning in a spatial task widely used to study
      hippocampal/cortical function. If cholinergic neurons contribute to learning and
      memory by integrated regulation of hippocampal and cortical processing, combined
      removal of hippocampal and cortical cholinergic projections might be necessary to
      produce impairment. However, this combined lesion failed to impair spatial
      learning. These data argue against the view that basal forebrain cholinergic
      deficiency plays a prominent role in disorders of learning and memory.

PMID- 8856690
TI  - Interaction between the intracellular Ca2+ stores in rat dissociated hippocampal
      neurones.
AB  - The interaction between the Ca(2+)-activated K+ currents (IK(Ca)) induced by
      acetylcholine (ACh), 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R)-ACPD)
      and caffeine in rat hippocampal CA1 neurones was investigated to examine the
      functional independence between IP3- and Ca(2+)-sensitive Ca2+ stores.
      Pretreatment with either ACh or (1S,3R)-ACPD almost completely suppressed the
      subsequent IK(Ca) induced by another. Pretreatment with caffeine partially
      suppressed the IK(Ca) induced by either ACh or (1S,3R)-ACPD, although the
      inhibitory effect varied among the neurones, while pretreatment with either ACh
      or (1S,3R)-ACPD also partially inhibited the caffeine-induced IK(Ca). Continuous
      treatment with ryanodine and thapsigargin nonselectively decreased both the
      caffeine- and ACh-induced IK(Ca). These results thus indicate a close interaction
      between IP3- and Ca(2+)-sensitive stores and also suggest that the relative size
      of both stores and the closeness between them differ among neurones.

PMID- 8856691
TI  - Neuromuscular function impairment is not caused by motor neurone loss in FALS
      mice: an electromyographic study.
AB  - Dominant mutations of human Cu/Zn superoxide dismutase (SOD1) are found in about
      20% of patients with familial amyotrophic lateral sclerosis (FALS). A transgenic
      mouse model of FALS (FALSG93A mice) has been generated by overexpression of a
      mutated form of SOD1. Using electromyography we first show that FALSG93A mice
      suffer from motoneurone dysfunction similar to that observed in ALS patients and
      fulfill Lambert's criteria for ALS. We also showed that FALSG93A mice demonstrate
      a massive loss of functional motor units starting at 47 days of age. Impairment
      of motor neurone function preceeds by 6 weeks the onset of apparent clinical
      signs (shaking, tremor) and the beginning of motor neurone loss. Neuromuscular
      deficits in FALS mice do not result from motoneuronal cell death but rather from
      loss of axonal integrity.

PMID- 8856692
TI  - The Kolliker-Fuse nucleus mediates the trigeminally induced apnoea in the rat.
AB  - The present study examined whether the Kolliker-Fuse nucleus (KF) plays a role in
      mediating the trigeminally induced apnoea which occurs after noxious perturbation
      of the nasal mucosa. We stimulated the ethmoidal nerve (EN5) electrically and
      recorded respiratory responses before and after injections of the calcium channel
      blocker CoCl2 into the KF. Unilateral EN5 stimulations resulted in an apnoea or
      in a reduction of respiratory frequency and tidal volume. EN5 stimulations
      immediately after ipsilateral CoCl2 injections into the caudal KF caused only
      minor respiratory suppression, indicating a blockade of synaptic transmission.
      Recovery of the respiratory responses was observed 15-120 min after the CoCl2
      injection. Our data strongly suggest that the caudal KF is an obligatory relay
      site for trigeminally induced apnoea.

PMID- 8856693
TI  - Mediodorsal thalamic evoked responses in the rat prefrontal cortex: influence of
      the mesocortical DA system.
AB  - The prefrontal cortex (PFC) receives a dopaminergic (DA) innervation from the
      ventral tegmental area (VTA) and is reciprocally connected with the mediodorsal
      thalamic nucleus (MD). The present study was performed in anaesthetized rats to
      determine the influence of the mesocortical DA system on excitatory responses
      evoked in the PFC by stimulation of MD: (1) short latency (< 4 ms) responses
      resulting from activation of the MD-PFC pathway; (2) long latency responses (> 10
      ms) resulting from activation of recurrent collaterals of PFC neurons projecting
      to MD. Local DA application and VTA stimulation did not affect short latency
      responses but blocked long latency responses. These results suggest that the
      mesocortical DA system inhibits excitations by recurrent collaterals of the PFC
      MD neurones but not the excitatory MD inputs to the PFC.

PMID- 8856694
TI  - Pleasure-attenuation of startle is disrupted by lesions of the nucleus accumbens.
AB  - The nucleus accumbens (NAC) and the amygdala have been implicated in processes by
      which reinforcers control instrumental behaviour. Reinforcement has both
      motivational and motor components, and it is necessary to differentiate between
      these two aspects. The acoustic startle response (ASR) is attenuated in the
      presence of a secondary reinforcer. In contrast to other paradigms used for
      investigating mechanisms of reward, the "pleasure-attenuated startle" (PAS)
      paradigm indicates the rewarding properties of a treatment by an attenuation
      rather than by reinforcement of a response, thus allowing determination of the
      motivational impact of a treatment independent from its motor stimulating
      effects. Here, we report that the ASR was attenuated in the presence of a
      positive conditioned stimulus in shamoperated animals and in rats with lesions of
      the amygdala, but not in animals bearing 6-hydroxydopamine lesions of the NAC.
      These findings suggest that the catecholaminergic innervation of the NAC is
      important for behavioural control by conditioned reward.

PMID- 8856695
TI  - Do amphibians have a true locus coeruleus?
AB  - Much controversy surrounds the identity of a locus coeruleus in amphibians
      because although previous studies on the isthmic region of the brain of anurans
      and urodeles revealed the presence of noradrenergic cell bodies they failed to
      demonstrate their projection to the telencephalon or the spinal cord. In the
      present study applications of Texas Red-conjugated dextran amines to the basal
      telencephalon or to the spinal cord in combination with tyrosine hydroxylase
      immunohistochemistry revealed that the noradrenergic cell bodies in the isthmic
      region of anuran (Rana perezi) and urodele (Pleurodeles waltl) amphibians project
      to the telencephalon as well as to the spinal cord. On the basis of location,
      neurotransmitter content and efferent projections, the isthmic noradrenergic cell
      group of amphibians is, therefore, considered homologous to the locus coeruleus
      of amniotes.

PMID- 8856696
TI  - The effects of mitochondrial failure upon cholinergic toxicity in the nucleus
      basalis.
AB  - Increased glutamate or acetylcholine receptor stimulation may interact with
      mitochondrial failure to increase the vulnerability of cholinergic neurons within
      the nucleus basalis. Understanding of the mechanisms that underlie this
      vulnerability may lead to a therapy to prevent the degeneration of these neurons
      in Alzheimer's disease. In the presence of a mitochondrial energy deficit, excess
      stimulation of N-methyl-D-aspartate (NMDA) receptors was not required for
      cytotoxicity. Furthermore, stimulation of cholinergic receptors was cytotoxic to
      cholinergic neurons but this toxicity was not enhanced by NMDA stimulation.
      Chronic administration of NMDA antagonists, such as memantine, amantadine or MK
      801, attenuated the effects of mitochondrial failure in the presence or absence
      of excessive cholinergic or NMDA receptor stimulation.

PMID- 8856697
TI  - m-Chlorophenylpiperazine (mCPP) is an antagonist at the cloned human 5-HT2B
      receptor.
AB  - The behavioural effects of m-chlorophenylpiperazine (mCPP) in rats and its
      clinical effects in man are thought to be related to its action at 5-HT2B/2C
      receptors. However, although mCPP is a partial agonist at these subtypes in rat,
      its efficacy at human 5-HT2B/2C receptors is unknown. We therefore investigated
      the activity of mCPP at cloned human 5-HT2B and 5-HT2C receptors. mCPP was a
      partial agonist at the human 5-HT2C receptor but antagonized the human 5-HT2B
      receptor. Therefore, while supporting the proposal that at least some of the
      clinical effects of mCPP are likely to be mediated via stimulation of the 5-HT2C
      receptor, this study also suggests that any 5-HT2B receptor-mediated effects are
      more likely to result from receptor blockade than from receptor activation.

PMID- 8856698
TI  - bFGF enhances the protective effects of MK-801 against ischemic neuronal injury
      in vitro.
AB  - The neuroprotective activity of basic fibroblast growth factor (bFGF) in
      combination with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 was
      evaluated in organotypic hippocampal slice cultures. Oxygen/glucose deprivation
      produced neuronal damage which was assessed using propidium iodide fluorescence.
      Treatment with increasing doses of bFGF demonstrated significant neuroprotection
      that was optimal at 10 ng ml-t. This effect was diminished at higher
      concentrations. MK-801, at the optimal concentration of 30 microM, demonstrated
      greater neuroprotective efficacy than bFGF. However, bFGF significantly enhanced
      the protection conferred by MK-801 alone. These results suggest that neurotrophic
      factors such as bFGF may augment the neuroprotective effects of NMDA antagonists
      against ischemic neuronal injury.

PMID- 8856699
TI  - An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat.
AB  - Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) cleaves pro-IL-1 beta to
      produce mature IL-beta, and is a member of a family of proteases implicated in
      apoptosis. Intracerebroventricular (i.c.v.) administration of an irreversible ICE
      inhibitor, z-VAD-DCB (1 pmol, 30 min before and 15 min, 2, 4, 6 and 8 h after
      surgery) markedly reduced (50 +/- 4%, p < 0.001) infarct volume measured 24 h
      after focal cerebral ischaemia (middle cerebral artery occlusion, MCAo) in the
      rat. Inhibition of damage was observed in the cortex (51 +/- 5% reduction) and
      striatum (42 +/- 6% reduction). These data implicate ICE in ischaemic neuronal
      death in vivo. Inhibition of ICE could reduce ischaemic damage either by
      preventing IL-1 beta synthesis or by inhibiting apoptosis or by both of these
      processes, and may provide a useful therapeutic approach to the inhibition of
      ischaemic brain damage.

PMID- 8856700
TI  - Convulsant and anticonvulsant actions of agonists and antagonists of group III
      mGluRs.
AB  - Group III metabotropic glutamate receptors (mGluR4, 6, 7, 8) are negatively
      coupled to adenylate cyclase and, when activated presynaptically, decrease the
      release of glutamate and GABA. We have used intracerebroventricular injections of
      agonists and antagonists believed to act selectively on these receptors to study
      the pro- or anti-convulsant effects of mGluR III activation in nonepileptic
      (Swiss-Webster) and epileptic (DBA/2) mice. In both mouse strains the prototypic
      agonists L-2-amino-4-phosphonobutanoate (LAP4) and L-serine-O-phosphate are
      proconvulsant. The supposed antagonists (S)-2-methyl-2-amino-4-phosphonobutanoate
      (MAP4) and (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG), have a
      predominantly proconvulsant effect. (S)-alpha-methyl-3-carboxyphenylalanine,
      which is a potent and selective antagonist for LAP4 in the cortex, is
      anticonvulsant in DBA/2 mice and decreases the convulsant effect of N-methyl-D
      aspartate, 3,5-dihydroxyphenylglycine, LAP4 and MPPG in Swiss-Webster mice. These
      data suggest that reduced inhibitory transmission may be more significant than
      reduced synaptic release of glutamate following group III mGluR activation.

PMID- 8856701
TI  - Cellular localization of neuropeptide-Y receptors in the rat hippocampus: long
      term effects of limbic seizures.
AB  - To clarify the cellular localization of neuropeptide-Y receptor subtypes in the
      dentate gyrus and CA3 sector of the rat dorsal hippocampus and their changes
      after kainic acid-induced seizures, we used receptor autoradiography to measure
      [125I]PYY binding to Y1 and Y2 receptors after colchicine treatment. Fifteen days
      after colchicine infusion in the dorsal hippocampus granule cells and their mossy
      fibres degenerated while the hilar interneurons and CA3 pyramidal cells were
      spared. This treatment markedly decreased [125I]PYY binding to Y1 receptors in
      the molecular layer of the dentate gyrus (-82%) and in the hilus (-70%).
      [125I]PYY binding to Y2 receptors was reduced by 40% and 48%, respectively, in
      the CA3 region and in the hilus. Thirty days after kainic acid treatment,
      [125I]PYY binding to Y1 receptors was decreased by 35% in the molecular layer of
      the dentate gyrus whereas the binding to Y2 receptors was increased by 116% in
      the hilus. The effect of colchicine in kainic acid-treated rats indicates that
      these plastic changes occur selectively on granule cell projections.

PMID- 8856702
TI  - Male sexual behaviour not abolished after medial preoptic lesion in adult rats.
AB  - N-methyl-D-aspartic acid (NMDA) was injected into the medial preoptic area (mPOA)
      of 10 rats to destroy the neurones in this region. Male sexual behaviour was
      scored before, and on days 2, 6, 10, 17, 24 and 31 after the administration of
      NMDA. The neurones in the injection site were destroyed in all the rats, but male
      sexual behaviour was only transiently reduced in the animals with lesions largely
      restricted to the mPOA. These findings are in contrast to the earlier reports of
      permanent suppression of sexual behaviour after electrolytic lesion, with damage
      to the neurones and fibres of passage. The present study shows that the mating
      behaviour could be expressed even after the destruction of the neurones in the
      mPOA.

PMID- 8856703
TI  - Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally
      but not centrally.
AB  - Peripheral and central injections of recombinant rat interleukin-1 beta (IL-1
      beta) have been shown to decrease social exploration in rats. To test the
      involvement of vagal afferents in the communication between the immune system and
      the brain, sham-operated and vagotomized rats were injected peripherally or
      centrally with physiological saline or IL-1 beta 4 weeks after surgery. Vagotomy
      attenuated the depression in social exploration induced by i.p. administration of
      IL-1 beta (15 micrograms) but did not alter the behaviour-depressing effects of
      an intracerebroventricular (i.c.v.) injection of IL-1 beta (45 ng). These results
      confirm the role of vagal afferent nerves in the transmission of an immune
      message from the periphery to the brain, and show that vagotomy does not impair
      the direct sensitivity of the brain itself to immune signals.

PMID- 8856704
TI  - Evidence that short ACTH fragments enhance vestibular compensation via direct
      action on the ipsilateral vestibular nucleus.
AB  - The aim of the present study was to determine whether administration of the
      synthetic ACTH-(4-9) analogue, Org 2766, directly into the ipsilateral vestibular
      nucleus complex (VNC), would enhance vestibular compensation following unilateral
      labyrinthectomy (UL). Either artificial cerebrospinal fluid (ACSF; n = 4) or Org
      2766 (0.67 nmol kg-1 every 4 h for 52 h; n = 4), was administered directly into
      the VNC via a stainless steel cannula connected to an osmotic minipump implanted
      s.c. Three symptoms of UL, spontaneous ocular nystagmus (SN), roll head tilt
      (RHT) and yaw head tilt (YHT), were measured at 10, 20, 25, 30, 40, 45 and 50 h
      post-UL. Org 2766 produced a significant decrease in the frequency of SN and
      accelerated its compensation. Org 2766 had no significant effect on either the
      compensation of RHT or YHT. This result suggests that vestibular compensation is
      enhanced by short ACTH fragments as a result of direct action on the ipsilateral
      VNC itself.

PMID- 8856705
TI  - The cervicothalamic tract terminates in Cat301-sparse regions of the cat VPL.
AB  - The termination pattern of the cervicothalamic tract (CTI), labelled with
      anterogradely transported WGA-HRP, was compared with the immunolabelling pattern
      obtained with the monoclonal antibody Cat301 in adjacent sections through the
      ventral posterolateral nucleus (VPL). CTT terminations are located in peripheral
      parts of the medial and lateral parts of the VPL (VPLm and VPL1), being more
      extensive in the caudal than in the rostral parts of the subnuclei, and in the
      dorsal part of VPL1 and dorsolateral part of VPLm, regions that are all sparse in
      CAt301 immunoreactivity. Central regions of the VPL with dense Cat301
      immunolabelling contain only very sparse CTT termination. Thus, our findings show
      that the CTT innervates a compartment of the VPL that is characterized by sparse
      Cat301 immunoreactivity.

PMID- 8856706
TI  - An I2 imidazoline ligand, RS 45041, potentiates hyperalgesia in acute arthritis.
AB  - Descending inhibition is increased after the induction of inflammation of the
      knee. The present study investigated whether this effect is mediated through
      alpha 2-adrenoceptors and/or I2 imidazoline receptors in the rat. An alpha 2
      adrenoceptor antagonist, RX 821002, a selective I2 imidazoline ligand, RS 45041,
      and idazoxan, which has affinity for both these receptor types, were
      administered. After the induction of acute arthritis by intra-articular injection
      of kaolin and carrageenan, the agents binding to I2 imidazoline receptors further
      reduced the paw withdrawal latency to radiant heat beyond that induced by acute
      arthritis, i.e. these drugs were pronociceptive, potentiating hyperalgesia. These
      results suggest that I2 imidazoline receptors have an important role to play in
      modulation of hyperalgesia during acute inflammation. Development of I2
      imidazoline drugs may prove useful in the treatment of hyperalgesia.

PMID- 8856707
TI  - Nerve length and volume in synaptic vs diffusion neurotransmission: a model.
AB  - Non-synaptic diffusion neurotransmission (NDN) may be an important factor in
      brain space and energy conservation, especially within cell assemblies and for
      mass sustained functions. We have illustrated the extreme cases of total synaptic
      and total ND neurotransmission for the purpose of noting the differences between
      the two. For these modeling studies, in which we assume assemblies of 1000 to 100
      000 cells supplied by at least one fiber and a single synapse from each of the
      other cells, each cell assembly would have approximately 200 m to 8000 km of
      nerve fibers more than when innervated by diffusion. For coeruleo-cortical
      synaptic innervation, linking each to a common origin (the locus coeruelus), the
      fiber lengths are 38 cm (1000 cells) to 170 m (100,000 cells). It is likely ,
      however, that neuronal arrays include both 'wireless' (NDN) as well as synaptic
      intercellular communication systems.

PMID- 8856708
TI  - Mu and delta opioid receptor gene expression after chronic treatment with opioid
      agonist.
AB  - Levels of mRNA coding for mu and delta opioid receptors were evaluated by
      competitive PCR in regions of rat brain where adaptive changes in opioid
      regulation of adenylyl cyclase occur following chronic morphine treatment.
      Correlation between receptor protein and mRNA levels after exposure to full and
      partial agonists were also investigated in NG108-15 cells. Different basal gene
      expression levels of mu and delta opioid receptors were found in the caudate
      putamen, nucleus accumbens, thalamus and periaquaductal gray. After continuous
      morphine treatment for 7 days both mu and delta opioid receptor mRNA levels were
      unchanged in all four regions compared with saline-treated controls. In NG108-15
      cells marked down-regulation of delta opioid receptors as measured by radioligand
      binding was observed after 5 or 24 h full agonist (D-Ser3-Leuenkephalin; DSLET)
      treatment. Morphine, a partial agonist at delta receptors, did not reduce
      receptor number at either time point. The reduction in delta receptor binding
      after DSLET treatment was not accompanied by significantly diminished levels of
      delta receptor mRNA. Unaltered mu and delta receptor mRNA levels in brain after
      chronic morphine exposure make it unlikely that adaptive changes in the
      transcription of these genes play a role in the observed tolerance in opioid
      regulation of adenylyl cyclase.

PMID- 8856709
TI  - Viable cultured neurons in ambient carbon dioxide and hibernation storage for a
      month.
AB  - Neurobasal is a bicarbonate-buffered medium optimized for the growth of embryonic
      rat hippocampal neurons at pH 7.3 in 5% CO2. Neurons die within hours in this or
      in other 26 mM bicarbonate buffers when transferred to ambient CO2 (0.2%). Death
      is associated with a rapid rise in medium pH to 8.1. A new CO2-independent
      modification of Neurobasal (Hibernate E), when supplemented with B27, can
      maintain neuron viability for at least 2 days in ambient CO2. This same medium
      can also be used to store viable brain tissue for up to a month with
      refrigeration. These advances should facilitate studies of neuron physiology
      outside the incubator as well as storing and transporting neuronal tissue.

PMID- 8856710
TI  - Non-conscious choice in cutaneous backward masking.
AB  - A simple but effective method has been devised to explore backward masking in
      cutaneous sensation. In this method a weak electrical shock to the palm (test
      stimulus) is followed by a stronger shock to the same site (masking stimulus). By
      combining this stimulation strategy with a choice reaction time paradigm, it has
      been possible to show that the nervous system responds to the test stimuli even
      though they are not consciously perceived. Further, the distribution of errors in
      the different types of trial suggests that, under these experimental conditions,
      the identification of the stimulus and the choice of response may also be made at
      a non-conscious level. A tentative scheme for the timing of the various neural
      events is proposed.

PMID- 8856711
TI  - Event-related gamma band activity during passive and active oddball tasks.
AB  - The EEG was recorded during passive listening and active attending to tone pips
      of an oddball stimulus sequence, and the time course of event-related gamma band
      activity (30-60 Hz) was compared with event-related potential (ERP) components.
      In the conventional frequency range (0.1-4.3 Hz) mismatch negativity (MMN) was
      produced in the passive listening condition. Concurrent with MMN, the power of
      event-related gamma activity to the deviant stimulus was higher than gamma
      activity elicited by the preceding standard stimulus. The transition from the N2b
      to the P3 wave, produced during active attention, was associated with a decrease
      in gamma band power upon the deviant tone. The results show the differential
      generation of gamma band power depending on preattentive and attentive stimulus
      processing.

PMID- 8856712
TI  - Analgesic effects of adenosine during exercise-provoked myocardial ischaemia.
AB  - The analgesic potential of adenosine during myocardial ischaemia was studied in
      patients with coronary artery disease and exercise-limiting angina pectoris.
      Patients were given a low dose of adenosine or placebo in a double-blind cross
      over fashion by continuous i.v. infusion before and during two exercise tests.
      Adenosine decreased chest pain by 45 +/- 13% (p < 0.02) while heart rate-blood
      pressure product and electrocardiographic signs of myocardial ischaemia did not
      change. Ten healthy volunteers received increasing doses of adenosine by
      continuous i.v. infusion. The heat pain threshold increased in skin covering the
      chest (p < 0.03) and also tended to increase at the left thenar eminence (p <
      0.07). In conclusion, the neuromodulator adenosine can therefore act as an
      analgesic in myocardial ischaemia.

PMID- 8856713
TI  - Remyelination in the CNS of the hypothyroid rat.
AB  - A number of studies have provided good evidence to indicate a role for thyroid
      hormone in myelination. Since myelination and remyelination have many shared
      objectives, and may therefore involve similar mechanisms, we examined whether
      thyroid hormone may also have a role in remyelination by both Schwann cells and
      oligodendrocytes of spinal cord axons that had been demyelinated by the injection
      of ethidium bromide in thyroidectomized rats. Neither the extent of
      oligodendrocyte remyelination nor the thickness of myelin sheath formed by
      remyelinating oligodendrocytes was affected by hypothyroidism. However, the
      extent of remyelination carried out by Schwann cells was decreased in hypothyroid
      rats compared with normal control animals.

PMID- 8856714
TI  - Extraocular proprioception is required for spatial localization in man.
AB  - We studied the effect of extraocular muscle deafferentation on the performance of
      manual pointing to foveated visual targets at different craniotopic locations.
      Five patients who underwent unilateral thermocoagulation of the trigeminal nerve
      (V) for trigeminal neuralgia were tested before and after surgery. Only the group
      of patients with postsurgical corneal anaesthesia, attesting to involvement of
      the ophthalmic branch (which carries the ocular proprioceptive fibres), presented
      deficits in accuracy of pointing. The position of initial and final pointing was
      shifted toward the lesioned side predominantly in the ipsilateral hemispace.
      These data support a model in which balanced ocular proprioceptive inputs are
      required for accuracy of visually guided movements in egocentric space.

PMID- 8856715
TI  - Glutamatergic projections from the rostral hypothalamus to the periaqueductal
      grey.
AB  - Retrograde transport of fluorescent latex microspheres was combined with
      immunocytochemistry for glutamate to determine the organization of the
      projections from glutamate-containing neurones in the rostral hypothalamus to the
      different subdivisions of the periaqueductal grey (PAG). Double-labelled
      neurones, i.e. neurones immunoreactive for glutamate and projecting to the PAG,
      were found throughout the rostral hypothalamus. There were no apparent
      differences, however, in the origins of presumed glutamatergic projections from
      the rostral hypothalamus to the different subdivisions of the PAG.

PMID- 8856716
TI  - Trypsin promotes C6 glioma cell proliferation in serum- and growth factor-free
      medium.
AB  - C6 glioma cells could be successively subcultured and maintained in serum- and
      growth factor-free medium (SF/GFF medium). C6 cell proliferation in SF/GFF medium
      was positively correlated with the initial cell density at plating. This
      correlation disappeared when the medium had been renewed early after cell
      adhesion (3 h after plating), suggesting that C6 cell growth depends on some
      diffusible factor in the medium before renewal, and that this factor is not
      secreted from C6 cells in the assay culture but is transferred from the cell
      suspension. The supernatant of trypsinized C6 cell suspension (SCS), trypsin-EDTA
      solution for routine cell harvesting use, and modified trypsin of protein
      sequencing grade all promoted C6 cell proliferation at, appropriate dilutions or
      concentrations under SF/GFF conditions. The growth promoting effects of SCS and
      trypsin-EDTA solution were completely inhibited by soybean trypsin inhibitor.
      These results demonstrate that the serine protease trypsin has a proliferative
      effect on C6 cells continuously subcultured in SF/GFF medium. In addition, it is
      suggested that trypsin used for cell dispersion is transferred from cell
      suspension into the culture, where it promotes C6 cell growth after passage in
      our SF/GFF subculture system.

PMID- 8856717
TI  - Putative neuroendocrine cells in the Aplysia cerebral ganglion.
AB  - We report on a special population of cells in the Aplysia cerebral ganglion that
      are characterized by several features compatible with neuroendocrine function.
      These cells can be recognized in living ganglia by their small size, white color
      and their typical distribution as a compact cluster in the central medial region
      of the dorsal ganglion surface. Upon intracellular recording, these cells
      generate action potentials of relatively long duration (about 25 ms), as compared
      with the faster action potentials of larger white cells or of non-white cells
      (about 4 ms). Intracellular injection of the small white cells with Lucifer
      yellow after recording revealed a dual projection area: single cells have one
      process which branches extensively into many varicose terminals as it courses
      through the neuropil, and then sends varicose terminals to the vascular sheath at
      the periphery of the ganglion. In cryostat sections, these cells were
      specifically characterized by their content of large granules, the staining
      characteristics of which distinguish them from lipochondria or lysosomes. Their
      ability to bind fluorochromes nonspecifically is of particular importance for the
      interpretation of histochemical localization studies based on immunofluorescence
      techniques.

PMID- 8856718
TI  - Origin of thalamocortical projections to the presupplementary motor area (pre
      SMA) in the macaque monkey.
AB  - The presupplementary motor area (pre-SMA) is a recently defined cortical motor
      area that is located immediately rostral to the supplementary motor area (SMA)
      and is considered to play more complex roles in motor control than the SMA. In
      the present study, we examined the distribution of cells of origin of
      thalamocortical projections to the pre-SMA in the macaque monkey. Under the
      guidance of intracortical microstimulation mapping, the retrograde tracer
      biotinylated dextran amine was injected into the pre-SMA. Retrogradely labeled
      neurons were distributed primarily in the parvicellular division of the
      ventroanterior nucleus (VApc), oral division of the ventrolateral nucleus (VLo),
      area X, and mediodorsal nucleus (MD). Some labeled neurons were also observed in
      the medial and caudal divisions of the ventrolateral nucleus. The results
      indicate that the pre-SMA may receive not only basal ganglia inputs via the VApc,
      VLo, and MD, but also a cerebellar input via the X.

PMID- 8856720
TI  - The role of the external nucleus of the inferior colliculus in the construction
      of the superior collicular auditory space map in the guinea-pig.
AB  - In the guinea-pig two subcortical structures have been shown to contain
      representations of auditory space, the deep layers of the superior colliculus
      (SC) and the external nucleus of the inferior colliculus (ICX). The following
      investigation was undertaken to determine if the ICX influences the development
      of the SC auditory space map. A portion of the ICX was lesioned unilaterally when
      guinea-pigs were between 8 and 13 days old. Following a period of recovery, the
      SC mapping experiments commenced in the adult guinea-pig. Electrophysiological
      auditory responses were recorded from the deep layers of the SC to free-field
      azimuthal auditory stimulation. The data from the ICX lesioned animals revealed
      that the spatial tuning parameter values of the auditory receptive fields from
      the SC were significantly greater than those recorded in the normal control group
      of animals. The pooled data from the ICX lesioned group indicated that the peak
      angle of the response of the auditory receptive fields did not display normal
      topographic order. Furthermore, in several cases where the ICX lesion site was
      small, the position of the lesion could be correlated with the site of SC
      auditory space map disruption. These data indicate that, during early
      development, the presence of the ICX is essential for the normal emergence of an
      azimuthal map of auditory space in the deep layers of the guinea-pig SC.

PMID- 8856719
TI  - GTP-binding protein activation underlies LTP induction by mast cell degranulating
      peptide.
AB  - Mast cell degranulating peptide (MCD) induces long-term potentiation (LTP) in the
      CA1 region of the hippocampus. MCD has been shown to bind to a voltage-dependent
      A-type potassium channel with high-affinity (less than 1 nM). However, the
      concentration necessary to induce LTP is more than 500 nM, suggesting that some
      other functions of MCD are also fundamental to LTP induction. The concentration
      of MCD required for LTP induction was greatly reduced by preactivating G
      proteins. This fact suggests that G protein activation by MCD also plays an
      important role in LTP induction. MCD-binding proteins were purified from rat
      brain. G proteins were found to exist in a non-denatured state in this affinity
      purified fraction. When reconstituted into a planar lipid bilayer membrane, a
      potassium-selective and voltage-dependent current could be observed. This channel
      was blocked by MCD at a high concentration equal to the effective concentration
      for G protein activation. Addition of GTP-gamma-S significantly blocked the
      reconstituted current. Thus, we identified a pathway for LTP induction by MCD in
      which high concentrations of MCD activate G protein which in turns leads to
      blocking of a potassium channel.

PMID- 8856721
TI  - Exogenous estrogen acts differently on production of estrogen receptor in the
      preoptic area and the mediobasal hypothalamic nuclei in the newborn rat.
AB  - Expression of the estrogen receptor (ER) in the preoptic area (POA) and the
      mediobasal hypothalamus (MBH) in newborn female rats was studied by
      immunohistochemistry (IHC) and in situ hybridization histochemistry (ISHH). The
      number of ER immunoreactive (ER-IR) cells decreased and expression of ER mRNA was
      suppressed in the arcuate (ARH) and the ventromedial (VMH) hypothalamic nuclei by
      daily injections of estradiol benzoate (EB) for ten consecutive days. In
      contrast, in the POA, expression of ER mRNA was not suppressed by EB treatment,
      while the ER immunoreactivity and the number of ER-IR cells was decreased by EB
      treatment. Results of quantification of ER mRNA by reverse transcription
      polymerase chain reaction correlated well with results from ISHH: that is, ER
      mRNA expression decreased in the MBH but not in the POA. Thus, estrogen affects
      ER gene expression differently in these two brain regions.

PMID- 8856722
TI  - Cross axis vestibulo-ocular reflex induced by pursuit training in alert monkeys.
AB  - We examined the effect of conflicting vestibular and smooth pursuit information
      on the vestibulo-ocular reflex (VOR) in alert monkeys. Sinusoidal whole body
      rotation was applied either in the pitch or yaw plane while presenting a target
      spot that moved orthogonally to the rotation plane. The monkeys were rewarded for
      tracking the spot and eye movements induced by rotation alone were examined every
      15-30 min in complete darkness. Orthogonal eye movement responses to rotation
      were not observed before training but appeared after about 30 min of training.
      The gains (eye/chair) of the orthogonal component increased up to 0.2 after 1-2 h
      and were largest at the training frequency and approximately in phase with the
      stimulus; phase advanced at lower frequencies and lagged at higher frequencies.
      Amplitude tuning was also demonstrated when examined using different amplitudes
      at a constant frequency after training. Two hours of training to fixate an earth
      stationary spot projected onto a patterned visual background that moved
      orthogonally to the rotation plane during rotation, did not induce a cross axis
      response. These results indicate that pursuit training during VOR is effective in
      inducing cross-axis eye movement responses that are tuned to the metrics of the
      training stimulus.

PMID- 8856723
TI  - Trigeminocerebellar and trigemino-olivary projections in rats.
AB  - Retrograde and anterograde neuronal tracers (HRP, biocytin, biotinylated dextran
      amine) were used to study the organisation of trigeminocerebellar and trigemino
      olivary connections, focusing on the connectivity between trigeminal nuclear
      regions and the sagittal zones of the rat cerebellar cortex. Trigeminocerebellar
      projections were bilateral, but mostly ipsilateral. Direct trigeminocerebellar
      fibres originated mostly in the principal trigeminal nucleus (VP) and pars oralis
      (Vo), pars interpolaris (Vi), and to a lesser extent in pars caudalis (Vc) of the
      spinal trigeminal nucleus. Consistent projections were found from the Vc to
      cerebellar lobules IX and X. The trigeminal fibres terminated in the cerebellum
      in an organised fashion. The ventral part of the VP, Vo and Vi projected to the
      medial A zone and the C3 and D2 subzones, whereas the dorsal part of the nuclei
      projected to the lateral A zone and the C2, D0 and D1 subzones. In lobules IX and
      X, the organisation was different. The medial half of the VP, Vo, Vi and Vc
      projected to the lateral aspects of these lobules whereas their lateral part
      projected to their medial aspects. Trigeminal projections to the deep cerebellar
      nuclei were also present. Projections to a given sagittal zone concomitantly
      reached its corresponding nuclear target. Trigemino-olivary projections were
      principally contralateral. The Vo, Vi and Vc projected to the rostromedial dorsal
      accessory olive, the adjacent dorsal leaf and the dorsomedial part of the ventral
      leaf of the principal olive, which are known to project subzones C3, D0 and D1 of
      the rat cerebellar cortex.

PMID- 8856724
TI  - Spinal cord blood flow decreases following microinjection of sodium nitroprusside
      into the nucleus tractus solitarii of anesthetized rats.
AB  - This study was undertaken to examine whether or not nitric oxide (NO) is involved
      in synaptic transmission in the nucleus tractus solitarius (NTS) during control
      of the spinal cord circulation. Employing urethane-anesthetized, paralyzed and
      artificially ventilated rats, sodium nitroprusside (SNP), which produces NO, was
      microinjected unilaterally into the NTS and the spinal cord blood flow (SCBF) was
      determined using labeled microspheres. Arterial blood pressure (ABP) was
      decreased by unilateral microinjection of SNP into the NTS, but its value was
      kept within the normotensive range by blood transfusion, in order to measure SCBF
      at normotension. After microinjection of SNP into the NTS, the SCBFs of the
      cervical, thoracic and lumbar cords decreased significantly from 63 +/- 8 (mean
      +/- S.E.M.) to 49 +/- 7 (P < 0.05), from 54 +/- 7 to 37 +/- 7 (P < 0.05), and
      from 77 +/- 9 to 58 +/- 8 (P < 0.05) ml/min/(100 g), respectively (n = 10). Prior
      microinjection of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of the
      formation of NO from L-arginine, into the NTS blocked the spinal cord
      vasoconstrictor response produced by microinjection of L-glutamate into the NTS
      (n = 10). Prior microinjection of NG-monomethyl-D-arginine (D-NMMA), which does
      not inhibit the formation of NO from L-arginine, did not block the spinal cord
      vasoconstrictor response elicited by microinjection of L-glutamate (n = 11).
      Unilateral microinjection of L-NMMA into the NTS exerted no effect on the spinal
      cord circulation (n = 9). These findings suggest that NO may be involved in the
      control of the spinal cord circulation in the NTS.

PMID- 8856725
TI  - Coexistence of calcitonin gene-related peptide- and substance P-like
      immunoreactivity in retrogradely labeled superior spermatic neurons in the dog.
AB  - The coexistence of calcitonin gene-related peptide (CGRP) and substance P (SP)
      was determined in primary afferent neurons of the superior spermatic nerve of the
      dog. Testicular afferent neurons were visualized by retrograde labeling with the
      fluorescent dye fast blue. CGRP-like immunoreactivity (LI) was found in about 80%
      of testicular L1 and L2 dorsal root ganglion cells, and 81% of CGRP-positive
      neurons also contained SP. Conversely, SP-LI was found in 66% of testicular
      afferents, and 96% of SP-positive neurons simultaneously contained CGRP. Both
      CGRP- and SP-LI were observed in the whole size range of the testicular afferent
      neurons. No significant difference in the diameter was detected between CGRP- and
      SP-positive testicular afferent neurons. In contrast, the diameter of SP-positive
      cells was significantly smaller than that of CGRP-positive cells in the whole
      population of dorsal root ganglion (DRG) neurons. Compared to skin and muscle
      afferents, a larger population of the testicular afferents contain these
      peptides. This is considered to be one of the characteristic features of visceral
      afferents. Coexistence of CGRP and SP in testicular afferent neurons suggest a
      close functional relationship between these two neuropeptides in the sensory
      nervous system.

PMID- 8856726
TI  - Activity of the intercostal muscle spindle afferents in the lower thoracic
      segments during spontaneous breathing in the cat.
AB  - Intraaxonal recordings of 33 spindle afferents from the inspiratory (n = 8) and
      expiratory (n = 25) intercostal muscles in the lower thoracic segment (T9-11),
      were made during spontaneous breathing in the anesthetized cat. All of them
      showed respiration-related activity. However, only three spindle afferents (one
      from the inspiratory and two from the expiratory intercostal muscles) showed
      higher firing frequency during the active contraction phase of the receptor
      bearing muscle. The remaining 30 spindle afferents (seven from the inspiratory
      and 23 from the expiratory muscles) showed the maximum firing discharge during
      the passive stretch phase of the parent muscles. On the other hand, in the middle
      thoracic segments (T6-7), five of six spindle afferents from the inspiratory
      muscles and four of nine spindle afferents from the expiratory muscles showed
      maximum firing rate during parent muscle contraction in agreement with previous
      study. These results suggest that the spindle activity in the lower thoracic
      segments is dominated by muscle length changes, whereas that in the middle
      thoracic segments is largely via the fusimotor pathway.

PMID- 8856727
TI  - Neurotoxicology: The Cinderella of neuroscience.
AB  - This commentary wishes to open a discussion to identify new paths for progress in
      neurotoxicology research and to better face some criticism and inquiry from
      outside observers, particularly from those of closely related neurosciences.
      Examples representative of research in neurotoxicology as carried out over the
      last 20 years are presented. They are ranked, according to their approaches, into
      three main categories: molecular-mechanistic research, correlative research and
      black box research. There are many reasons for the relatively modest achievements
      of neurotoxicology as compared to those in other neuroscience fields. Most
      studies tend to be superficial and fail to address important biological questions
      because the pressure of politics demands swift and practical solutions to
      problems. Also, little advantage was taken from the interdisciplinary nature of
      neurotoxicology. A happy ending is possible when neurotoxicology research is
      encouraged within the mainstream of neurobiology, thus actively participating in
      the continuing neuroscience revolution.

PMID- 8856728
TI  - 6-Hydroxydopamine-mediated induction of rat brain metallothionein I mRNA.
AB  - Oxidative stress, resulting either from excess generation or reduced scavenging
      of free radicals, has been proposed to play a role in damaging striatal neurons
      in Parkinson's disease. Since metallothionein is able to regulate the
      intracellular redox potential, we have undertaken a group of experiments to learn
      whether or not 6-hydroxydopamine, which generates free radicals and is toxic to
      dopaminergic neurons, could alter the levels of zinc and metallothionein in the
      brain. The lesioning of the rat striatum with 6-hydroxydopamine (8.0 micrograms
      in 4 microliter 0.02% ascorbic acid) resulted in a reduction in the levels of
      zinc and metallothionein in the striatum but not other brain regions tested.
      However, the intracerebroventricular administration of 6-hydroxydopamine, in a
      dosage regimen that does not lesion catecholaminergic pathways but causes
      oxidative stress, enhanced dramatically the level of metallothionein I mRNA in
      some brain areas such as hippocampus, arcuate nucleus, choroid plexus, and
      granular layer of cerebellum, but not in the caudate putamen. The results of
      these studies are interpreted to suggest that zinc or metallothionein are altered
      in conditions where oxidative stress has taken place. Moreover, it is proposed
      that areas of brain, such as striatum containing high concentrations of iron, but
      low levels of inducible metallothionein are particularly vulnerable to oxidative
      stress.

PMID- 8856729
TI  - Tetrandrine blocks voltage-dependent calcium entry and inhibits the bradykinin
      induced elevation of intracellular calcium in NG108-15 cells.
AB  - Tetrandrine, a plant alkaloid used in Chinese traditional medicine blocks voltage
      dependent Ca2+ entry in NG108-15 cells as assessed using fura-2 microfluorimetry.
      Cells were depolarized with 50 mM KCI for one min resulting in a transient
      increase in the 340/380 nm ratio of fura 2 fluorescence, indicative of an
      increase in [Ca2+]i. Treatment of the same cell with 100 microM tetrandrine for
      seven min followed by an identical K+ depolarization blocked the increase in
      340/380 nm fluorescence ratio. Washing with tetrandrine-free solutions for 20 min
      partially reversed this effect. Bradykinin (Bk) induces transient and repetitive
      increases in [Ca2+] due to release of Ca2+ from intracellular stores via
      activation of the inositol trisphosphate (IP3) second messenger system. After pre
      treatment with 100 microM tetrandrine for seven min, the Bk (1 microM, 1 min)
      response was significantly reduced. Likewise, the effect of angiotensin II (AT
      II), which also causes an IP3 dependent release of Ca2+ from intracellular
      stores, was ablated by tetrandrine. Thus, in addition to block of voltage
      dependent Ca2+ channels, tetrandrine also caused disturbances in intracellular
      Ca2+ signalling.

PMID- 8856730
TI  - Increased inorganic mercury in spinal motor neurons following chelating agents.
AB  - Heavy metal toxicity has been implicated in the pathogenesis of motor neuron
      diseases. In an attempt to assess the efficacy of chelating agents to remove
      mercury from motor neurons, we quantitated the effect of the chelating agents
      meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3- dimercaptopropane -1-sulphonate
      (DMPS) on the burden of inorganic mercury in mouse spinal motor neurons. Mice
      were injected intraperitoneally with 1.0 mg HgCl2/kg body weight and one week
      later with either 4,400 mg/kg DMPS, 3,600 mg/kg DMSA or 5% NaHCO3 (control) over
      4 weeks. Mercury deposits in motor neurons of 50 micron frozen sections of lumbar
      spinal cord were visualised with an autometallographic technique. Optical
      sections of silver-enhanced deposits were acquired using a confocal microscope in
      reflective mode and the volume of the deposits within the perikaryon was
      estimated. Mercury deposits occupied significantly more volume in motor neurons
      after both DMPS (7.4%, SD +/- 0.7%) and DMSA (8.0% +/- SD 0.7%) treatment than in
      controls (4.3%, SD +/- 1.7%). The higher levels of neuronal inorganic mercury may
      be due to increased entry of mercury into motor axons across the neuromuscular
      junction as a result of chelator-induced elevated circulating mercury.

PMID- 8856731
TI  - Exposure to threshold doses of nicotine in utero: III. Augmentation of the
      prolactin and ACTH response to 8-OH DPAT by desipramine treatment is compromised
      in adult male offspring.
AB  - Gravid female rats were injected subcutaneously with saline (SAL) or nicotine
      (3.0 mg/kg and 0.05 mg/kg, bid) from days 14-21 of gestation. Adult 105-day old
      male offspring from each of the three groups were treated daily with saline or
      desipramine (DMI) (10 mg/kg, sc) for 14 days. Twenty-four hours after the last
      injection, animals were challenged with saline or 8-hydroxy-2- (di-n-propylamino)
      tetralin (8-OH DPAT) (0.1 mg/kg, sc), a serotonin IA(5-HT(IA)) agonist, and
      plasma prolactin and ACTH concentrations were measured 15 minutes later. DMI
      treatment augmented both the prolactin and ACTH responses to 8-OH DPAT in the SAL
      controls. Neither the prolactin nor the ACTH response was augmented significantly
      in the animals exposed prenatally to either nicotine dosage regimen, although
      there was a strong trend for the augmentation to occur in the low-dose nicotine
      exposed animals. The results indicate the capacity of 5-HT systems to adapt
      normally to DMI administration, as manifested by neuroendocrine responsivity to 8
      OH DPAT, was compromised in adult animals exposed to nicotine in utero.

PMID- 8856732
TI  - Neuronal loss in hippocampus in rats exposed to toluene.
AB  - Both clinical and epidemiological studies of the effects of exposure to toluene
      have shown that long-term exposure may result in chronic toxic encephalopathy,
      where one of the major symptoms is memory deficits. We have attempted to identify
      the structural basis of the toxic effects of toluene in the hippocampus, a region
      of the brain known to be involved in learning and memory processes and well
      suited for stereological analysis. Rats were exposed to 1500 ppm of toluene, six
      hours per day, five days per week for six months. This was followed by a four
      month-period without exposure prior to sacrifice. The total number of neurons in
      each of the five subdivisions of hippocampus of six exposed and six control rats
      was estimated with the optical fractionator. A statistically significant neuron
      loss of 16% was found in regio inferior (CA3 and CA2) of the exposed rats.

PMID- 8856733
TI  - Color vision loss among styrene-exposed workers neurotoxicological threshold
      assessment.
AB  - Styrene represents nowadays one of the most used organic solvent. The current
      exposure limit proposed for this chemical differs significantly from country to
      country: the Threshold Limit Value-Time Weighted Average (TLV-TWA) proposed by
      the American Conference of Governmental Industrial Hygienists (ACGIH) is 50 ppm
      while the German, Finnish and Swedish occupational exposure limit is 20 ppm.
      Nevertheless, effects on the nervous system were recently reported in workers
      exposed at TWA styrene levels below the current TLV. Neuro-optic pathways have
      been shown to be particularly vulnerable to organic solvent exposure. Analysis
      and measurements of visual functions can provide important information on early
      neurotoxic effects. Previous studies support the hypothesis that styrene exposure
      can induce a dose-dependent color vision loss. The aim of this study is to assess
      a threshold level below which no detectable effect occurs for color vision. We
      applied a sub-application of the change point problem in two-phase regression
      considering one phase as a constant line. In accordance with this model the
      maximum-likelihood technique was used as a method to examine the dose- effect
      relationship between external styrene exposure and chromatic discrimination. The
      present article presents a joint analysis of data from two previously published
      studies, one carried out in Canada and the other in Italy. The age and seniority
      of the workers from both countries were remarkably similar, as were the process
      type, the chemicals used and the work-tasks of exposed subjects. The mathematical
      method presented here shows the existence of a statistically significant
      threshold. This finding shows that, in fiberglass-reinforced plastics industry,
      visual color impairment could be significantly detected above 4 ppm (upper limit
      of the confidence interval at 5% = 26 ppm). The exact clinical meaning of this
      effect, and also the progress of the impairment in exposed workers, is still to
      be assessed in further studies. The results of our study support the need of a
      reduction of the occupational limits for styrene in workplaces to values close to
      or lower than German, Finnish or Swedish exposure limits.

PMID- 8856734
TI  - The effects of dextromethorphan on kainic acid-induced seizures in the rat.
AB  - Several studies have shown that dextromethorphan (DM) has both anticonvulsant and
      proconvulsant effects depending on the animal model. In this study, we examined
      the effects of DM on three parameters associated with kainic acid (KA)-induced
      seizures: cell loss in the hippocampus, increased AP-1 DNA binding activity and
      increased c-Jun and fos-related antigen (FRA) expression. KA administration (8
      mg/kg, ip) produced robust behavioral convulsions lasting 4-6 hr. Pretreatment
      with DM (12.5-75 mg/kg, po) 15 min before KA injections reduced the seizures as
      well as mortality in a dose-dependent manner. Histological studies revealed a
      severe loss of cells in the CA1 and CA3 fields of the hippocampus in KA-treated
      rats. DM pretreatment also reduced this cell loss in a dose-dependent fashion.
      Biochemical studies showed that DM pretreatment also attenuated the KA-induced
      increase of AP-1 binding activity and c-Jun/FRA expression in the hippocampus.
      These results indicate that DM is an effective antagonist of KA.

PMID- 8856735
TI  - Cardiorespiratory effects of cocaine and procaine at the ventral brainstem.
AB  - The caudal ventrolateral medulla (CVLM) is an area of the brainstem, in the
      vicinity of the hypoglossal nerve roots, where cholinergic and adrenergic neurons
      participate in respiratory and vasomotor control. Cardiorespiratory depression
      has been produced by topical application of cocaine to the CVLM. In the present
      studies, the effects of topical pretreatments of the CVLM with alpha-adrenergic
      blockers (prazosin 4.8 mM) and beta-adrenergic blockers (propranolol 11.3 mM) on
      the cardiorespiratory responses to topically administered cocaine (37 mM) were
      investigated in urethane anesthetized cats. Both prazosin and propranolol failed
      to produce ventilatory responses and to counteract cocaine-induced apneustic
      breathing. However, the cocaine-induced decrement in mean arterial blood pressure
      (MABP) following pretreatment of the CVLM with propranolol was found to be 11 +/-
      5%, compared to the 18 +/- 5% decrement produced by cocaine alone. These
      differences were not statistically significant. Procaine (37 mM) in equimolar
      doses to cocaine, produced a small statistically significant decrement in MABP (P
      < 0.05) without ventilatory effects. Topical administration of procaine (73.3
      mM), at approximately twice the equimolar dosage of cocaine, produced apneustic
      breathing that was indistinguishable from that produced by cocaine. The
      neurotoxic properties of cocaine that produce apneustic breathing appear to be
      similar to that produced by the anesthetic agent procaine, and the alpha- and
      beta-adrenoceptor blockers prazosin and propranolol do not appear to antagonize
      the vasomotor depression induced by cocaine at the CVLM.

PMID- 8856736
TI  - Decreased GAP-43 accumulation in neurite tips of cultured hippocampal neurons by
      acrylamide.
AB  - The critical axonopathy- producing effect of acrylamide (ACR) is hypothesized to
      be an interruption of fast vesicular transport resulting in a deficiency of
      distal axonal proteins. This study used the accumulation of growth associated
      protein- 43 (GAP-43) in neurite tips of cultured hippocampal neurons as a model
      to examine the effect of an ACR block of fast transport on the eventual protein
      concentration within the distal axon. Twenty-four hour incubation with ACR
      produced a dose-dependent reduction with 0.5mM and 1.0mM concentrations in the
      percent of neurites with a terminal GAP-43 accumulation. No change in cell size
      (area), cell body GAP-43 fluorescence, distal neurite fluorescence, absolute tip
      fluorescence or neurite length were observed. Another known inhibitor of
      transport, colchicine (COL) also caused a significant decrease in the percent of
      neurites with a GAP-43 accumulation; propionamide (PA), a non-neurotoxic analogue
      of ACR, had no effect on protein accumulation. These findings support the
      hypothesis that the disruption of fast transport by ACR can lead to depletion of
      vital proteins in the distal axon.

PMID- 8856737
TI  - GAP-43 mRNA expression in the developing rat brain: alterations following lead
      acetate exposure.
AB  - The developmental neurotoxicity of environmental lead exposure manifests as
      alterations in neural functioning and perturbed axonal and dendritic development.
      To examine the hypothesis that such lead-induced alterations in the neural
      network are associated with an altered mRNA expression of a specific neural cell
      growth associated protein, mRNA levels of GAP-43 (growth associated protein 43)
      were measured in the cortex and hippocampus of developing Long-Evans hooded rats
      following various lead exposure paradigms. Postnatal developmental profiles (PND
      6, 9, 12, 15, 20, and 25) of mRNA expression were generated following either
      prenatal (gestational day 13 to birth), postnatal (postnatal day 1 to postnatal
      day 20), or perinatal (gestational day 13 to postnatal day 20) exposure to lead
      acetate (0.2% in the drinking water of the dam). In control rats, GAP-43 mRNA
      levels displayed a distinct developmentally regulated profile of expression in
      both the cortex and hippocampus, characterized by an elevated level of expression
      within the first week of life. This peak level of expression was significantly
      depressed following either postnatal or perinatal exposure to lead acetate, while
      prenatal lead exposure produced an initial elevation of GAP-43 mRNA on postnatal
      day 6 followed by a sharp decline. These data suggest that lead exposure results
      in altered mRNA expression of a specific neural cell growth associated protein
      critical to the normal process of development. This perturbation in expression
      may play a role in the previously reported effects of lead acetate on axonal
      elongation during development of the nervous system and the subsequent alteration
      in nervous system functioning.

PMID- 8856738
TI  - Systemic application of pyrethroid insecticides evokes differential expression of
      c-Fos and c-Jun proteins in rat brain.
AB  - Expression of the c-Fos and c-Jun transcription factor was investigated by
      immunocytochemistry in the thalamus, hypothalamus, hippocampus and cortex of
      adult rats following intraperitoneal application of proconvulsant doses of the
      pyrethroid insecticides, cypermethrin and permethrin. Pyrethroid insecticides are
      used world-wide and their uptake, e.g., by nutrition and inhalation evokes severe
      neurological symptoms in animals and humans, but their effects on neuronal gene
      expression has not been elucidated. Cypermethrin induced a strong expression of c
      Fos and c-Jun in all the thalamic nuclei, except the ventro-posterior complex and
      substantia nigra, and in all the hypothalamic nuclei. In general, the
      immunoreactivities (IR) persisted for 8 h on their maximal levels, and were still
      above control levels after 24 h in several thalamic and hypothalamic areas. c-Fos
      IR was strongly increased in all cortical layers with a predominance in the
      superficial layers II-IV, whereas c-Jun-IR was only slightly increased. In the
      hippocampus, cypermethrin induced a weak expression of c-Fos, but not of c-Jun,
      in the dentate gyrus and CA-3 area. Permethrin that has a lower pharmacological
      potency, evoked a similar pattern of c-Fos and c-Jun expression, however,
      intensity and persistence of the neuronal labeling were less pronounced. Our
      results demonstrate that the neurotoxic effects of pyrethroid insecticides
      comprise molecular genetic alterations in the brain such as early and lasting
      induction of Fos and Jun transcription factor proteins. These changes in the
      neuronal program are prominent in the hypothalamus and thalamus that are involved
      in the regulation of the autonomic and visceral nervous systems.

PMID- 8856739
TI  - Characterization of the MDCK cell line for screening neurotoxicants.
AB  - The adoption of cell culture models to screen putative neurotoxicants is
      recognized in view of the consequences of nerve damage by environmental
      chemicals. Developing cell culture models that mimic certain properties of the
      blood-brain barrier (BBB) would be especially useful in view of the barrier's
      strategic role in the neurotoxic process. The present study evaluates a kidney
      epithelial cell line for its functional and enzymatic resemblance to cerebral
      endothelial cells. Madin-Darby canine kidney (i.e., MDCK) cells display
      morphological (i.e., ultrastructurally defined tight junctions), enzymatic
      (acetylcholinesterase, butyrylcholinesterase, gamma-glutamyl transpeptidase,
      superoxide dismutase, alkaline phosphatase, lactate dehydrogenase), and antigenic
      cell markers (i.e., Factor VIII), also found in cerebral endothelial cells. In
      addition, MDCK cells develop electrical resistance which is increased in response
      to conditioned media from astroglial cell lines (i.e., C6). These results suggest
      that the MDCK cell line might be useful for identifying neurotoxic chemicals that
      affect BBB integrity through similar endpoints.

PMID- 8856740
TI  - Lead-induced changes in dopamine D1 sensitivity: modulation by drug
      discrimination training.
AB  - Prior studies have reported that Pb exposure results in enhanced sensitivity to
      both D1 and D2 dopamine agonists as indicated by left shifts of the dose-effect
      functions for the discrimination of these agonists from saline in drug
      discrimination procedures (Cory-Slechta and Widzowski, 1991). To further
      determine mechanisms of such Pb-induced changes in dopamine system functions,
      this study evaluated the potential contribution to Pb-induced D1 supersensitivity
      of:i) synergistic D1-D2 receptor interactions, and ii) the effects of the chronic
      D1 agonist administration inherent in the drug discrimination procedures
      themselves. As in Cory-Slechta and Widzowski (1991), rats exposed from weaning to
      50 or 150 ppm Pb acetate in drinking water and trained using standard operant
      drug discrimination procedures to discriminate 6.0 mg/kg of the partial D1
      agonist SKF38393 from saline showed greater sensitivity to SKF38393 (left-shifted
      dose effect curves) than did the 0 ppm group. To determine the role of D1/D2
      interactions in this supersensitivity, SKF38393 dose-effect curves of the groups
      were compared in the presence and absence of a dose of 0.04 mg/kg of the D2
      antagonist haloperidol. The impact of the chronic administration of the D1
      agonist utilized in drug discrimination training was determined by comparing the
      dose-effect curves of the groups before and after a 24 day period of
      discontinuation of drug discrimination training. D1/D2 interactions do not appear
      to contribute to Pb-induced enhancement of sensitivity to the D1 agonist
      SKF38393, as it was maintained even in the presence of the D2 antagonist
      haloperidol. Discontinuation of drug discrimination training resulted in
      sensitization in control but not Pb-treated rats, a pattern indicative of Pb
      induced D1 subsensitivity. These data raise questions about the depletion of
      dopamine (DA) availability as a mechanism of Pb-induced alterations in DA system
      function and suggest that Pb-induced D1 supersensitivity may represent altered
      effects of chronic D1 administration imposed on DA systems modified by Pb
      exposure per se.

PMID- 8856741
TI  - Neurotoxicity induced by prenatal aluminum exposure in rats.
AB  - Aluminum has been implicated as a neurotoxic agent in a number of experimental
      laboratories and epidemiological studies. Dementia has been correlated to
      elevated aluminum levels in Alzheimer's disease and has been related to impaired
      motor function and to a number of cognitive deficits in both humans and animals.
      To determine the neurotoxicity of aluminum (Al) lactate exposure in rat pups,
      postnatal behavioral effects of 0, 2.5, 5, 10 mg/kg daily s.c. treatment during
      gestation days 7th-15th were investigated. Offspring were tested for motor
      coordination, stress tolerance in a swimming test, behavioral patterns in an open
      field, in the acquisition and extinction of an avoidance responding and in a
      reconditioning task. In the open field test the horizontal activity was
      diminished at the top dose of Al exposure. The motor coordination and the stress
      tolerance were not altered by prenatal Al treatment. The main sign of
      neurotoxicity was diminished performance and lengthened latency in an avoidance
      responding task in all treated groups. Our findings confirm that postnatal
      behavioral effects can be induced in offspring prenatally exposed to aluminum
      lactate.

PMID- 8856742
TI  - Neuropathological changes in rat brain following oral administration of 2
      chloropropionic acid.
AB  - The agrochemical intermediate, L-2-Chloropropionic acid (L-2-CPA) and D-2
      chloropropionic acid (D-CPA), when administered separately by oral gavage to
      rats, produced extensive cerebellar granule cell necrosis (> 80%) characterised
      by varying degrees of nuclear condensation and nuclear karyorrhexis. In contrast
      a few necrotic Purkinje cells (< 5%) were observed. Purkinje cell damage
      consisted of cytoplasmic and nuclear shrinkage and hyperchromasia. Karyorrhexis
      was not seen in Purkinje cells. Extensive vacuolation (edema) was present both in
      the cerebellar granular layer and Purkinje cell layer. Astrogliosis (hypertrophy
      and hyperplasia) was seen at lesion sites and activity was recognised by positive
      glial fibrillary acidic protein (GFAP) staining. Proliferative activity of
      astrocytes at lesion sites was confirmed by positive proliferating cell nuclear
      antigen (PCNA) immunostaining. Astrogliosis was focused exclusively in the
      necrotic granule cell layer. A single oral dose of 750 mg/kg of either
      stereoisomer or three consecutive daily doses of 250mg/kg L-2-CPA. produced the
      lesion. Cerebellar water content increased with time in parallel with the
      edematous response noted by neuropathological examination. The earliest onset of
      the lesion was observed at 36 hours appearing more extensive at 48 and 72 hours
      post-dosing. No other major neuropathological changes were detected in the brain,
      spinal cord, spinal ganglia, Gasserian ganglia, peripheral nerves and voluntary
      muscle following L-2-CPA administration. In conclusion, both stereoisomers of CPA
      were found to be selective neurotoxicants of the rat central nervous system.

PMID- 8856743
TI  - A dynamic model of the blood-brain barrier "in vitro".
AB  - Cell culture models have been widely used for screening of neurotoxicants and
      represent a viable alternative to direct in vivo experiments. We have developed a
      dynamic in vitro blood-brain barrier model designed to allow for extensive
      toxicological, pharmacological and physiological testing. Induction of blood
      brain barrier properties in a tri-dimensional hollow fiber culturing apparatus
      was investigated by co-culturing a bovine aortic endothelial cell line (or rat
      brain endothelial cells) with rat brain astrocytes (or C6 rat glioma cells) under
      pulsatile flow conditions to mimic intraluminal blood flow. Cell growth was
      monitored over time by measuring glucose consumption and lactate production:
      these experiments confirmed that the hollow fiber cell culturing systems can
      maintain viable cells in culture for extended (> 1 month) periods of time. Cells
      were visually inspected after culturing and dissociation from the hollow fiber
      cartridge and identified as endothelial (by fluorescent Dil-Ac-LDL uptake) or
      glial (by GFAP immunoreactivity). Blood-brain barrier properties were tested by
      intraluminal injection of horse-radish peroxidase (HRP, mol. weight 44,000),
      glucose (m.w. 180) or potassium. Either procedure demonstrated that aortic cells
      co-cultured with astrocytes (or C6 cells) developed a selective barrier with an
      estimated electrical resistance of 2,900 omega/cm2. The electrophysiological and
      morphological properties of BAEC were also affected by the co-culturing process,
      suggesting that astrocytes induced CNS properties in these cells. These results
      demonstrate that the hollow fiber cell co-culturing system may be used as a
      dynamic model of the mammalian blood-brain barrier.

PMID- 8856744
TI  - Characterization of the morphological variations of astrocytes in culture
      following ethanol exposure.
AB  - The nervous system is one of the main targets of ethanol toxicity and it has been
      suggested that astrocytes might play an important role as their integrity is
      essential for the normal growth and functioning of neurons. Morphological
      variations of astrocyte cultures were therefore examined after exposure to
      various doses of ethanol (0.5, 1 and 2%) for different durations (24, 48, 72 and
      96 h). The percentage of cell viability and the cell density were calculated and
      the changes in astrocyte morphology were assessed by an image analysis system
      (Samba 2005) allowing the characterization of 5 parameters (perimeter, surface,
      elongation factor, convexity factor and the form factor) of a great number of
      cells (over 6500). This was necessary because of the high variability in normal
      cultured astrocyte morphology. A two-way statistical approach (2-factors ANOVA
      completed by stepwise discriminant analysis) was adopted to emphasize the
      differences between control and exposed cells. In such conditions, ethanol
      treated cells became more elongated, less circular and more concave and did not
      grow like non-exposed cells. The mean pooled values of these parameters tended to
      be modified as a function of the dose of ethanol. The relationships between
      parameters clearly separated the groups as a function of the different doses.
      Finally no significant difference was observed in cell viability and cell density
      despite lower scores in the groups exposed to the highest dose of ethanol for the
      longest time. Our results suggest that ethanol might affect astrocytes in two
      different but probably complementary ways by modifying the cell shape and by
      altering normal cell development.

PMID- 8856745
TI  - Postweaning lead exposure enhances the stimulus properties of N-methyl-D
      aspartate: possible dopaminergic involvement?
AB  - This study sought to determine whether previously reported Pb-induced biochemical
      changes in the NMDA receptor complex also resulted in changes in NMDA sensitivity
      in vivo. Rats chronically exposed to 0, 50 or 150 ppm Pb acetate in drinking
      water postweaning were trained to discriminate the stimulus properties of 30
      mg/kg NMDA from saline using standard operant food-reinforced drug discrimination
      procedures. Following acquisition of the discrimination, various doses of NMDA,
      of the competitive antagonist CPP, the D2 antagonist spiperone and the D1
      antagonist SCH23390 were substituted for the NMDA training dose and percent NMDA
      responding to each determined. In addition, the efficacy of CPP in antagonizing
      the NMDA stimulus was assessed. NMDA increased drug lever responding to levels >
      90%, an effect antagonized by CPP. Spiperone substituted for NMDA, whereas
      SCH23390 engendered partial substitution and CPP only minimal substitution. Pb
      exposure did enhance NMDA sensitivity, as indicated by an increased frequency of
      full NMDA substitution at lower NMDA doses, although the effect size was somewhat
      modest. Pb exposure, at least at one dose, also attenuated the substitution of
      spiperone for NMDA, raising the possibility that dopaminergic systems may be
      involved in mediating Pb-induced changes in NMDA sensitivity.

PMID- 8856746
TI  - Effects of organophosphate exposure on muscarinic acetylcholine receptor subtype
      mRNA levels in the adult rat.
AB  - Repeated exposure to organophosphorus (OP) insecticides results in a decrease of
      muscarinic acetylcholine receptors (MRs) in the central nervous system. OP
      induced MR down-regulation in vivo is modeled by chronic in vitro exposure to
      muscarinic agonists. Many studies, both in vivo and in vitro, indicate that the
      treatment-induced decrease in MR number is accompanied by a decrease in the mRNA
      levels of specific MR subtypes. In this study, the in vivo effects of OP exposure
      on the mRNA levels of three MR subtypes (m1, m2, and m3) were examined in brain
      tissue and in peripheral mononuclear cells, which express the m3 subtype. Adult
      male Sprague-Dawley rats were orally administered disulfoton (2 mg/kg/day) for 14
      days, and a subset of exposed animals was allowed to recover for 28 days. This
      treatment caused a 28% and 81% decrease, respectively, in [3H]-QNB binding and
      acetylcholinesterase activity in the cortex, similar to that observed in previous
      studies; after recovery, these levels had returned to 99% and 90%, respectively,
      of controls. There was a significant decrease in m1 mRNA levels in hippocampus
      (23%) after disulfoton treatment, while no change was observed in the cortex,
      corpus striatum, medulla, or cerebellum. The m2 subtype mRNA was significantly
      decreased in both hippocampus (24%) and medulla (19%), but not in cortex,
      striatum, or cerebellum. m3 mRNA levels were significantly decreased in cortex
      (10%), but no change was observed in hippocampus, medulla, cerebellum, or
      lymphocytes. After recovery, no differences in m1 or m3 mRNA levels were observed
      in any tissue examined, whereas the decrease in m2 mRNA in the hippocampus
      remained significant (29%). These results indicate that OP exposure can
      differentially regulate mRNA levels for MR subtypes in different brain areas, and
      suggest that m2 muscarinic receptors in the hippocampus are most affected by this
      treatment.

PMID- 8856748
TI  - Antimicrobial resistance: an overview.

PMID- 8856747
TI  - Exposure to methylmercury results in serum autoantibodies to neurotypic and
      gliotypic proteins.
AB  - Environmental exposure to methylmercury (MeHg) continues to pose a threat to
      humans, making early detection of neurotoxic effects a pressing concern. An
      enzyme-linked immunosorbent assay (ELISA) to measure serum autoantibodies (lg) to
      neurotypic and gliotypic proteins [neurofilament triplet (NF68; NF160; NF200),
      myelin basic protein (MBP) and glial fibrillary acid protein (GFAP)] as markers
      of subclinical neurotoxicity was developed and tested in Fisher 344 rats exposed
      orally to 16 or 32 ppm MeHg. Both levels of MeHg resulted in serum lg to all 5
      proteins, not normally seen in controls. For anti-NFs and anti-GFAP, lgM isotype
      predominated significantly (p < 0.05) over lgG. lg for MBP were of the lgG
      isotype, lgM were not detected. Significant differences (p < 0.05) between 16 and
      32 ppm MeHg in levels of anti-NF 68 and GFAP, lgM, were evident at 7 days of
      exposure, but not at 14 days. Anti-NF 160, lgM, was significantly (p < 0.01)
      elevated in rats exposed to 32 ppm vs 16 ppm at 14 days. However, at both dose
      levels anti-NF 68 titers were the most elevated of the three NF proteins (p <
      0.0001). For anti-NF 200 and anti-MBP it was the lgG isotype that was
      significantly (p < 0.01) elevated in the 32 ppm group at 7 days. GFAP levels as a
      marker of neurotoxicity were determined in the cortex, hippocampus and
      cerebellum. Exposure to 32ppm MeHg resulted in decreased (p < 0.05) levels in the
      cortex at 14 days. Both levels of MeHg resulted in increased GFAP in the
      cerebellum at 14 days. This study suggests that assay of autoantibodies against
      nervous system proteins may provide a means of assessing the early neurotoxic
      effects of environmental MeHg exposure.

PMID- 8856749
TI  - Mechanisms of bacterial antibiotic resistance.
AB  - Infectious complications are major contributing factors to morbidity and
      mortality in the ICU setting. Organisms frequently encountered in the ICU include
      Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae
      (particularly in trauma victims), enterococci, Klebsiella pneumoniae,
      Enterobacter spp., Acinetobacter baumanii, Escherichia coli, and Stenotrophomonas
      (Xanthomonas) maltophilia. Antibiotics have played a major role in the treatment
      of infections caused by such bacterial pathogens. Organisms have responded to the
      antibiotic challenge, however, evolving and developing resistance to all
      available antimicrobial agents to a greater or lesser degree. Specific mechanisms
      of resistance include reductions in cell-wall membrane permeability, alterations
      of antimicrobial agent target sites, enzymatic inactivation of antibiotics, and
      development of bypass pathways around antimicrobial targets. This article
      describes, pathogen by pathogen, antimicrobial agents that are useful for the
      treatment of infection in the ICU setting and the mechanisms whereby bacteria
      have short-circuited our antimicrobial armamentarium.

PMID- 8856750
TI  - A model of the transmission of antibiotic-resistant bacteria in the intensive
      care unit.
AB  - Antibiotic resistance is a growing problem, affecting microorganisms found both
      in hospitals and in the community. In most patients, resistant organisms arise by
      transmission of already resistant microorganisms from another person, rather than
      arising by mutation in the index patient. Antibiotic resistance genes are often
      borne on plasmids or transposons on which they may be spread rapidly to other
      organisms in the same species or in other species. Plasmids and transposons
      readily pick up genes for resistance to other antibiotics or nonantibiotic agents
      ("linked resistance"). Control of the spread of antibiotic resistance may require
      limitation of the usage of other agents with linked resistance as well as of the
      antibiotics of primary interest. A model is described for the analysis of the
      transmission of antibiotic-resistant enteric bacteria in the ICU. The model deals
      with the baseline level of antibiotic resistance in the "source" patient, the
      effect of antibiotics in augmenting the concentration of resistant organisms in
      that patient, the role of patient-to-patient contact, and factors which may
      influence the "colonizability" of the recipient patient. Possible measures to
      reduce the spread of antibiotic resistance are discussed. It is hoped that the
      model may serve to focus discussion on some key ingredients of the transmission
      cycle.

PMID- 8856751
TI  - Resistance to antifungal agents in the critical care setting: problems and
      perspectives.
AB  - As is the case with antibacterial agents, the increasing use of antifungal agents
      has led to development of antifungal resistance, the most clinically important of
      which is the resistance of Candida to fluconazole. While mutation to high-level
      fluconazole resistance is possible, the most important aspect of fluconazole
      resistance for patients in the ICU is the possibility of an epidemiologic shift
      away from such susceptible species as C. albicans and C. parapsilosis toward the
      most resistant species, such as C. glabrata and C. krusei. Resistance to
      amphotericin B by Candida is also possible, but less frequent. Strategies for
      treating invasive Candida infections must consider the relative rates of non-C.
      albicans Candida infection and the likelihood of antifungal resistance. The
      agents that cause invasive mold infections in the ICU are intrinsically
      moderately resistant to the available antifungal agents, and therapy depends less
      on the choice of antifungal therapy than on the correction of predisposing
      factors. The role of susceptibility testing as a guide in selecting appropriate
      therapy for all of these infections is as yet incompletely defined, but testing
      for resistance to fluconazole may soon be ready for clinical use.

PMID- 8856752
TI  - Could invasive diagnostic techniques for ventilator-associated pneumonia be
      associated with reduced antibiotic usage in the ICU?
AB  - ICUs are often viewed as the epicenter of bacterial resistance. Overuse of
      antibiotics is one factor associated with this characteristic; other such factors
      include overcrowding, suboptimal observance of hygienic practices, cross
      transmission of resistant strains, and high susceptibility of patients housed in
      ICUs. Evidence is scarce that different approaches to diagnosing infections,
      especially of the lower respiratory tract, can influence overall patterns of
      antibiotic usage and resistance. However, it is likely that more antibiotics are
      being administered to patients with suspected respiratory tract infections when
      diagnosed using nonspecific techniques than when more specific techniques are
      being used routinely. Additionally, the evidence is mounting that prior
      antibiotic usage is associated with increased risk of lower respiratory tract
      infection (LRTI), and also of infection caused by high-risk antibiotic-resistant
      pathogens, which in turn are associated with higher risk of treatment failure and
      mortality than their susceptible counterparts. A logical approach that may
      partially resolve this problem is to use specific diagnostic techniques, which
      will result in avoiding overtreating patients with suspected LRTI.

PMID- 8856753
TI  - Problems with resistance in pediatric intensive care.
AB  - Antibiotic resistance in the neonatal and pediatric intensive care environments
      has not been rigorously investigated. There is reason to believe that the
      epidemiology of antibiotic resistance in these settings may be different from
      that in other hospital settings because the patients' preadmission health status,
      the maturity of their immune systems, and their outpatient exposure to
      antibiotics are different from those seen in adults. At the present time, the
      areas of greatest concern are the outbreaks of infection caused by methicillin
      resistant Staphylococcus aureus in the neonatal ICUs and the emergence of
      antibiotic-resistant Gram-negative bacteria in pediatric intensive care units
      (PICU). In the former, colonization and transmission by nursery personnel remains
      one of the great challenges in infection control. In the latter, new information
      is emerging which challenges the notion that antibiotic-restriction policies
      might be an effective means for modulating the emergence of antibiotic-resistant
      Gram-negative pathogens in the pediatric intensive care environment. It appears
      that these organisms are largely imported into the ICU from the community and are
      not a result of antibiotic practices within the unit itself. This observation
      requires that strategies to control these organisms in the PICU be reassessed.

PMID- 8856754
TI  - Role of the microbiology laboratory in monitoring and identifying resistance: use
      of molecular biology.
AB  - Antimicrobial resistance is an increasing problem in the United States. Early
      detection of emerging trends in antimicrobial resistance may facilitate
      implementation of effective control measures. Most antimicrobial susceptibility
      testing is qualitative, in that it categorizes isolates as susceptible,
      intermediate, or resistant. This approach is relatively inexpensive and generally
      adequate for clinical purposes. Qualitative susceptibility testing has some
      limitations for monitoring for emerging resistance. Selective quantitative
      susceptibility testing may be useful in detecting early trends toward elevated
      minimal inhibitory concentrations. Molecular methods have a role also in
      characterizing mechanisms of resistance and in the typing of resistant strains to
      determine patterns of spread. Laboratory monitoring of emerging resistance must
      be associated with an effective infection control policy and a willingness to
      modify practice in a rational manner based upon the trends detected.

PMID- 8856755
TI  - Does antibiotic restriction prevent resistance?
AB  - Antimicrobial resistance among some hospital organisms has increased to a stage
      where it can no longer be tolerated. The need for preventive and corrective
      measures is urgent. There is an association between the use of antimicrobial
      agents and resistance that is likely causal. Alterations in antimicrobial usage
      have been shown to affect antimicrobial resistance rates, particularly with use
      of aminoglycosides. Efforts to improve antimicrobial use through educational
      efforts alone have been largely ineffective, even when coupled with quality
      management or clinical guideline aspects. Thus, further work is urgently needed
      to determine the impact of antimicrobial-use controls. Additional large-scale,
      well controlled trials of antimicrobial-use regulation employing sophisticated
      epidemiologic methods, molecular biological organism typing, and precise
      resistance mechanism analysis will be required to determine the best methods to
      prevent and control this problem and ensure our optimal antimicrobial-use
      "stewardship." Consideration of the long-term effects of antimicrobial selection,
      dosage, and duration of treatment on resistance development should be a part of
      every antimicrobial treatment decision.

PMID- 8856756
TI  - Efforts of pharmacy to reduce antibiotic resistance.
AB  - Pharmacists have an integral role in the care of ICU patients, including those
      with infections. Antibiotics continue to be among the most widely prescribed
      drugs in the ICU environment. This article focuses on the impact pharmacists have
      on the care and economics for the critically ill infected patient and on
      mechanisms used in hospitals to control antibiotic misuse. Numerous studies point
      to inappropriate antibiotic use and resultant selection pressure on antimicrobial
      resistance. The critical care pharmacist can impact this prescribing by assuring
      optimal pharmacotherapy specific for the organism and associated disease.
      Furthermore, policies have been implemented to modify antibiotic use, including
      formulary manipulations, antibiotic stop order forms, care plans, antibiotic
      cycling, oral switching, and computer-assisted antimicrobial therapy. Future
      research is needed to determine the optimal method for preventing resistance.
      However, a multidisciplinary approach to rational antimicrobial use is suggested.

PMID- 8856757
TI  - Vancomycin-resistant Enterococcus faecium infections in the ICU and
      quinupristin/dalfopristin.
AB  - The incidence of vancomycin resistance among enterococci, and Enterococcus
      faecium in particular, has increased sharply in the last few years. This shift
      toward infection with resistant Gram-positive organisms is thought to be the
      consequence of certain features specific to the intensive care setting: a high
      concentration of severely compromised patients; continued use of indwelling
      devices and invasive procedures; and widespread, empiric use of antimicrobial
      agents directed against Gram-negative bacilli. Measures that can be taken to
      prevent the development of bacterial resistance in the ICU include strict
      adherence to infection control policies and asepsis, and rational use of
      antibiotics. Current antimicrobial regimens for serious enterococcal infections
      consist of a combination of ampicillin, penicillin G, or vancomycin plus
      streptomycin or gentamicin. High levels of resistances among some enterococcal
      isolates, however, may render these strategies ineffective. A new agent,
      quinupristin/dalfopristin (RP 59500), has demonstrated encouraging in vitro
      activity against vancomycin-resistant E. faecium. Initial clinical reports,
      though limited, are similarly promising. Although phase III clinical trials with
      RP 59500 are not completed, the agent is available through an emergency-use
      program for patients with severe Gram-positive infections who cannot tolerate or
      do not respond to all other clinically appropriate antibiotics.

PMID- 8856758
TI  - The distribution, diagnoses and estimated economic impact of plant poisonings and
      mycotoxicoses in South Africa.
AB  - Maps are provided showing the national and provincial distributions of many plant
      poisonings and mycotoxicoses in South Africa. The various poisonings are briefly
      described and criteria for their diagnoses are given. The annual mortalities of
      cattle from plant poisonings/mycotoxicoses in South Africa were calculated as c.
      37 665 head with a current cash value of c. R57 627 450, and that of small stock
      as c. 264851 head with a value of c. R46 878 627. The annual total cost of plant
      poisonings/mycotoxicoses to the livestock industry of South Africa is
      conservatively estimated at R104 506 077. These figures do not include hidden
      losses such as diminished production, reproductive failure, the cost of not
      utilizing toxic pastures and the fall in price of infested land.

PMID- 8856759
TI  - The efficacy of amitraz against cattle ticks in Tanzania.
AB  - The efficacy of amitraz on cattle ticks was assessed by susceptibility tests,
      spraying and dipping trials. Tests on the susceptibility of three tick species,
      Rhipicephalus appendiculatus, Amblyomma variegatum and Boophilus decoloratus to
      amitraz (technical grade-purity 98.6% w/w) showed all 15 tick strains tested to
      be highly susceptible, with LC50 ranging between 0.001% and 0.03%, and LC99,
      between 0.01% and 0.07%. Spraying trials were carried out on calves infested with
      R. appendiculatus, A. variegatum and B. decoloratus. Amitraz wettable powder [as
      Taktic total replacement (TR)] was tested against B. decoloratus, and amitraz
      emulsifiable concentrate (as Taktic EC) against the other two species. Both
      formulations showed instant action, with ticks detaching from the calves between
      30 min and 8 h after spraying. More than 50% of the detached engorged females
      failed to lay eggs. The remainder laid few eggs, and these had a low hatching
      rate of 0-2%, compared with 90-98% in the controls. The detached nymphs failed to
      moult, and the males and non-engorged females also detached, were immobilized and
      finally died. In the dipping trials, cattle heavily infested with ticks (mean
      tick counts of about 800) were dipped once weekly in amitraz (Taktic TR). Weekly
      tick counts showed that the reinfestation rate was reduced to zero after the
      ninth dipping. The results of the three trials complement each other, showing
      that amitraz is at present effective in the control of African tick species on
      cattle in Tanzania.

PMID- 8856760
TI  - Demarcation of potentially mineral-deficient areas in central and northern
      Namibia by means of natural classification systems.
AB  - Mineral deficiencies that lead to production losses often occur concurrently with
      climatic and management changes. To diagnose these deficiencies in time to
      prevent production losses, long-term monitoring of mineral status is advisable.
      Different classification systems were examined to determine whether areas of
      possible mineral deficiencies could be identified, so that those which were
      promising could then be selected for further monitoring purposes. The
      classification systems addressed differences in soil, vegetation and geology, and
      were used to define the cattle-ranching areas in the central and northern
      districts of Namibia. Copper (Cu), Iron (Fe), zinc (Zn), manganese (Mn) and
      cobalt (Co) concentrations were determined in cattle livers collected at
      abattoirs. Pooled faecal grab samples and milk samples were collected by farmers,
      and used to determine phosphorus (P) and calcium (Ca), and iodine (I) status,
      respectively. Areas of low P concentrations could be identified by all
      classification systems. The lowest P concentrations were recorded in samples from
      the Kalahari-sand area, whereas faecal samples collected from cattle on farms in
      the more arid areas, where the harder soils are mostly found, rarely showed low P
      concentrations. In the north of the country, low iodine levels were found in milk
      samples collected from cows grazing on farms in the northern Kalahari broad
      leaved woodland. Areas supporting animals with marginal Cu status, could be
      effectively identified by the detailed soil-classification system of irrigation
      potential. Copper concentrations were lowest in areas of arid soils, but no
      indication of Co, Fe, Zn, or Mn deficiencies were found. For most minerals, the
      geological classification was the best single indicator of areas of lower
      concentrations. Significant monthly variation for all minerals could also be
      detected within the classification system. It is concluded that specific
      classification systems can be useful as indicators of areas with lower mineral
      concentrations or possible deficiencies.

PMID- 8856761
TI  - The usefulness of faecal phosphorus and nitrogen in interpreting differences in
      live-mass gain and the response to P supplementation in grazing cattle in arid
      regions.
AB  - The average daily gains of heifers and oxen on commercial and experimental farms
      in Namibia were used to indicate production differences in several areas and at
      different rates of phosphorus and protein supplementation. Faecal concentrations
      of phosphorus and nitrogen were used to indicate concentrations of these
      nutrients in grazing. Areas with high concentrations of nitrogen in faeces proved
      to support high levels of average daily gain. Animals responded positively to
      phosphorus supplementation only when faecal nitrogen concentrations were above 12
      g/kg DM. Nitrogen concentrations in faeces were directly related to average daily
      gain of heifers, but protein supplementation did not have a significantly
      positive effect on average daily gain.

PMID- 8856762
TI  - Screening of the venoms of two Parabuthus scorpion species on isolated
      cardiomyocytes.
AB  - Crude, diluted venoms of Parabuthus transvaalicus and P. granulatus were tested
      on isolated cardiomyocytes. Ventricular myocytes were subjected to
      hypercontractility tests and whole-cell voltage clamp. Both venoms had a profound
      influence on the hypercontractility of cardiomyocytes, which was markedly
      decreased when they were pre-absorbed with commercial antiserum. Whole-cell clamp
      results showed an increase in the sodium current, and a retardation of the time
      course of inactivation, implicating the presence of an alpha toxin in both
      venoms.

PMID- 8856763
TI  - The osteology of the African elephant (Loxodonta africana): vertebral column,
      ribs and sternum.
AB  - The vertebral column, sternum and ribs of the African elephant were studied and
      illustrated. In the cervical series, the vertebrae are characterized by very
      short (compressed) vertebral bodies and short spinous processes. There are 20-21
      thoracic vertebrae that carry ribs, and three lumbar vertebrae. The neural arches
      of the five sacral vertebrae fuse with each other as well as with the wings of
      the ilium, while the intervertebral discs do not ossify and the vertebral bodies
      remain separate. There are 19-21 caudal vertebrae. In the latter, the neural
      arches of only the first five to six vertebrae fuse dorsally, the vertebral
      foramens of the other vertebrae as well as the vertebral canal remain open
      dorsally. The body of the first rib is greatly expanded while that of the last
      three to four ribs are reduced. The cartilages of the first six ribs articulate
      with the sternum, the last five to six ribs do not bear costal cartilages and are
      not attached to the costal arch. The sternum consists of five sternabrae that
      form three approximately equal, but separate, segments. The first segment is
      formed by the first sternabra, the second segment is formed by the second to
      fourth sternabrae and the last segment is formed by the fifth sternabra. The
      first and second sternabrae articulate with each other by means of a synovial
      joint, the second to fourth sternabrae are fused to each other and the fourth and
      fifth sternabrae are loosely attached to each other by connective tissue.

PMID- 8856764
TI  - The comparative host status of red veld rats (Aethomys chrysophilus) and bushveld
      gerbils (Tatera leucogaster) for epifaunal arthropods in the southern Kruger
      National Park, South Africa.
AB  - Red veld rats (Aethomys chrysophilus) and bushveld gerbils (Tatera leucogaster)
      were trapped at monthly intervals, when possible, over a 2-year period, in the
      southern Kruger National Park, Mpumalanga Province. Forty-six specimens of each
      species were caught, euthenased and microscopically examined for fleas, lice,
      ticks and mites. Clear differences existed between the two rodent hosts in
      infestation intensity and also parasite species. The flea, Xenopsylla
      brasiliensis, commonly and exclusively utilized red veld rats, whereas Xenopsylla
      frayi was common and specific to bushveld gerbils. T. leucogaster were commonly
      infested with the lice Hoplopleura biseriata and Polyplax biseriata, while only a
      single A. chrysophilus hosted the louse, Hoplopleura patersoni. Red veld rats
      harboured small numbers of the immature stages of Haemaphysalis leachi/spinulosa
      and relatively large numbers of Rhipicephalus simus. The larvae of R. simus were
      irregularly collected from February to September and the nymphs from March to
      November. Bushveld gerbils hosted fewer ticks than did the rats, with a single
      specimen of H. leachi/spinulosa and low numbers of immature Hyalomma truncatum,
      the latter erratically present from June to October. Miles were abundant on both
      rodent hosts, A. chrysophilus hosting 13 species in six families, and T.
      leucogaster hosting 12 species representing seven families, with clear
      differences in mite assemblages between the two rodents. As the rats and gerbils
      were collected from the same trap lines at the same times, the differences in
      species composition and infestation intensity of their parasites, suggest that
      immunological behavioural or other segregating mechanisms are in operation to
      maintain discrete parasite assemblages.

PMID- 8856765
TI  - Heartwater in sheep and goats: a review.
AB  - Heartwater (cowdriosis) is an important, often fatal, tick-borne disease of
      domestic and wild ruminants in sub-Saharan Africa and some Indian Ocean and
      Caribbean islands. The causal agent, Cowdria ruminantium (Cowdry 1925), is a
      rickettsia closely related to members of the genus Ehrlichia, and is probably a
      part of a complex of genomic species. Imported breeds of sheep and goats
      (especially Angoras) are highly susceptible, but indigenous populations of
      endemic areas may be resistant to infection. Very young stock (less than 9 d old)
      possess a natural resistance that is unrelated to the immune status of the dams.
      Symptoms of heartwater vary, but usually begin with fever and may involve
      neurological signs and respiratory distress. Clinical diagnosis is based on
      symptoms, history of tick-exposure and post-mortem findings, and is confirmed by
      demonstration of characteristic rickettsial organisms in vascular endothelial
      cells. Laboratory diagnosis is retrospective and includes fluorescent antibody
      and enzyme-linked immunosorbent assays. Serological tests are compromised by non
      specific reactions with certain Ehrlichia spp. DNA and oligonucleotide probes
      have been developed, but are thus far unavailable in many countries affected by
      heartwater. Treatment with tetracyclines is effective if begun in the early
      stages of infection. Control is based on a knowledge of the disease cycle in
      nature, and is achieved through judicious tick control, vaccination or both. A
      virulent, blood-based vaccine is available. Existence of a carrier state in
      recovered animals, including wild ruminants, complicates control efforts, and
      eradication is feasible only in circumscribed foci. Problem areas in fundamental
      and applied research on heartwater, as it affects sheep and goats, are discussed.

PMID- 8856766
TI  - Selenium toxicosis with focal symmetrical poliomyelomalacia in postweaning pigs
      in South Africa.
AB  - An outbreak of paralysis in finisher pigs in South Africa after ingestion of feed
      containing 54,581 mg/kg of selenium is described. The main and entirely
      consistent lesion was bilaterally symmetrical focal poliomalacia of the ventral
      horns of the spinal cord, which was most severe and consistent in the lumbar
      intumescence. Acute and subacute lesions were characterized by malacia with large
      numbers of gitter cells. The main features of chronic lesions were loss of
      neurons and gliosis. Focal degeneration and necrosis of the myocardium and
      skeletal muscles were also consistent, but there were fewer specific changes.
      Endothelial swelling, mild fibrinoid degeneration and perivascular leukocytic
      infiltration were present in the acute stage. Dermatitis, coronitis and hoof
      sloughing, usually present in more chronic cases of intoxication, were not a
      feature of the present outbreak, although alopecia and crusting were evident on
      the backs of a few pigs several weeks after the episode of intoxication. Serum
      and tissue-selenium levels were elevated in the early stages after intoxication.
      Serum levels were nearly normal in chronic cases two months after the episode,
      while liver and kidney levels were still higher than normal. Higher levels were
      found in liver, kidney and serum than in muscle, with the highest levels in the
      kidney. Less than 20% of affected pigs recovered sufficiently to be marketed.

PMID- 8856767
TI  - Cryopreservation of sheathed third-stage larvae of Ancylostoma caninum (hookworm
      of dogs) and Ancylostoma tubaeforme (hookworm of cats).
AB  - Sheathed infective third-stage larvae of Ancylostoma caninum and Ancylostoma
      tubaeforme were successfully cryopreserved in liquid nitrogen. The survival
      rates, as assessed by motility, were A. caninum 49.2% and A. tubaeforme 51,5%
      after 30 d of cryopreservation.

PMID- 8856768
TI  - Brucella melitensis biotype 1 outbreak in goats in northern KwaZulu-Natal.
AB  - Brucella melitensis biotype 1 was confirmed in indigenous, outbred goats in three
      northern districts of the KwaZulu-Natal province following the diagnosis of human
      Malta fever in the same area. Six foci of infection were found during an
      extensive serological survey involving 6266 goats carried out in most of the
      districts of the KwaZulu-Natal province. The prevalence in the positive herds
      varied between 17% and 100%. The diagnosis was confirmed by culturing milk
      samples from serologically positive animals. Infected goats were found in only
      three districts (Ubombo, Ingwavuma and Pongola) and all infected herds fell
      within a 50-km radius.

PMID- 8856769
TI  - Managed care--orthopedists must clean own house first.

PMID- 8856770
TI  - Managed health care ideology--capitalism or communism?

PMID- 8856771
TI  - More comments on tennis calf or tennis leg.

PMID- 8856772
TI  - More comments on tennis calf or tennis leg.

PMID- 8856773
TI  - Quality improvement may be in the equation--but not for now.

PMID- 8856774
TI  - Biomechanical effects of gamma irradiation on fresh frozen allografts in vivo.
AB  - The effect of gamma irradiation on the mechanical properties of allograft in a
      rabbit model was examined. Tibial allografts were tested in torsion to failure to
      determine maximum torque and maximum stress. Statistically significant
      degradation in the torsional strength of irradiated tibias vs controls was
      demonstrated. Femoral allografts were orthotopically implanted into experimental
      rabbits and secured with an intramedullary pin. Rates of incorporation and
      failure patterns were significantly altered by irradiation. These data suggest
      that sterilization of fresh-frozen allografts with 2.5 Mrad or greater severely
      degrades the ability of the graft to resist torsion. The rate of incorporation of
      fresh-frozen allografts also may be dramatically decreased as a result of
      irradiation.

PMID- 8856775
TI  - Fractures in children treated with radiotherapy for soft tissue sarcoma.
AB  - There is a clear association between multimodal therapy for bone tumors and the
      development of skeletal complications; however, this has not been addressed in
      children with soft tissue sarcomas. We reviewed records of the 70 children
      treated for soft tissue sarcoma of the lower extremity at St. Jude Children's
      Research Hospital between 1962 and 1991. Of the 12 patients who received
      radiation after surgical excision of their tumors, three subsequently developed
      fractures. Two of the three had also received chemotherapy. Our findings indicate
      that, although the risk of fracture after therapy for soft tissue sarcoma may be
      multifactorial, radiation may play a significant role. Minimizing the size of
      surgical incisions, improving radiotherapy techniques, maximizing chemotherapy,
      and emphasizing physical therapy and appropriate follow up can all serve to
      decrease long-term toxicities. Such optimal use of therapy could subsequently
      reduce side effects, such as osteoporosis and muscle and bone atrophy, that
      predispose patients to fractures.

PMID- 8856776
TI  - Activity relationships of total hip arthroplasty in patients with osteonecrosis
      and osteoarthritis.
AB  - We compared the age adjusted results of all primary Osteonics total hip
      arthroplasties with osteonecrosis and osteoarthritis. The Harris index hip score
      was used for the analysis. Twenty-eight patients had osteoarthritis and 26
      patients had osteonecrosis. The Harris hip score was used to compare the
      osteoarthritis and osteonecrosis gross. Patients with osteoarthritis gradually
      increased in Harris hip score, whereas osteonecrosis patients gradually decreased
      in Harris hip score over 60 months. However, after the patients were adjusted for
      age above and below 50 years, the trend for each group was similar despite the
      diagnosis. All patients below 50 years of age, regardless of diagnosis, gradually
      decreased in hip score over time. On the other hand, all patients over 50 had a
      gradual increase in hip score with time. The poor results seen in patients with
      osteonecrosis may be related more to age and activity level than to the primary
      diagnosis. We do not believe that the diagnosis of osteonecrosis plays as
      significant a role in the final outcome of a total hip arthroplasty as does the
      patient's age and, more importantly, activity level following hip arthroplasty.

PMID- 8856777
TI  - Results of the total bi-metric cementless hip arthroplasty.
AB  - A 2.9-year follow up of 50 primary Bi-Metric System cementless, porous-coated hip
      arthroplasties (Biomet) is presented. Four patients were operated bilaterally. In
      two patients, revision arthroplasty was carried out, in one because of infection,
      in the other because of loosening of the stem. The average Harris hip score was
      96 points. The pain level according to d'Aubigne was 5.87. All patients belonged
      to Jensen's social function group 1. According to Engh's x-ray score, the femoral
      component achieved an average total of 19 points. Twenty-three patients with
      heterotopic ossification were graded according to Brooker et al; 18 patients
      belonged to group I-II, and 5 patients to group III. Discrepancy of leg length
      was measured in 20 patients, and averaged 0.52 cm (range: 0 cm to 2.5 cm). Four
      patients complained of thigh pain, but they had no radiographic evidence of
      loosening of components. The mean age was 63.4 years for women and 58.1 for men.
      Acceptably high Harris Hip Scores were obtained for the Bi-Metric hip prosthesis
      at 2-year follow up.

PMID- 8856778
TI  - Carpectomy and fusion in adult-acquired hand spasticity.
AB  - Five adult patients with voluntary hand control, complicated by severe flexion
      contracture and spasticity secondary to brain injury, underwent subtotal
      carpectomy and radio-carpal or radio-metacarpal fusion. None of the patients were
      capable of functional prehension before surgery, and all had difficulty with
      hygiene due to their deformity. The deformities were beyond the scope of
      correction with soft tissue release. Two of the patients had previously undergone
      flexor-pronator origin release, musculo-tendinous lengthening of the wrist and
      finger flexors, or a combination of both. All five patients progressed to union
      without complication. Four achieved meaningful gains in functional grasp-release
      of the hand following the surgery.

PMID- 8856779
TI  - Fibrous dysplasia.
AB  - Fibrous dysplasia provides the orthopedic surgeon with tremendous reconstructive
      challenges. The manifestations of the condition are very diverse and often
      involve organ systems not routinely cared for by the orthopedic surgeon. We
      present a concise review of the radiography, histology, clinical manifestations,
      and complications of this condition, with the main focus on the non-orthopedic
      management challenges.

PMID- 8856780
TI  - Chronic postpartum pelvic pain treated by surgical stabilization.

PMID- 8856781
TI  - Lawn mower injury resulting in Chopart amputation in a young child.

PMID- 8856782
TI  - Radiographic progression to dorsal intercalated segment instability.
AB  - We present a case of an acute hyper-extension wrist injury that progressed from
      normal carpal alignment to dorsal intercalated segment instability over a short
      period of time. Disruption of the scapholunate interosseous and radioscapholunate
      ligaments was proven arthroscopically, while the intercapsular ligaments were
      demonstrated to be intact. We have shown that lunate malalignment can occur over
      time, as secondary lunate ligamentous supports attenuate under abnormal carpal
      kinetics.

PMID- 8856783
TI  - Radiologic case study. Tuberculous osteomyelitis and arthritis.

PMID- 8856784
TI  - Establishing a universal protocol for deep vein thrombosis following orthopedic
      surgery: total knee arthroplasty.
AB  - The incidence of deep vein thrombosis (DVT) after total knee replacement surgery
      is reported to occur in 84% of all unprotected patients and may be as high as 68%
      in patients who receive DVT prophylaxis. Moreover, controversy exists as to which
      pharmacologic or mechanical agent is most effective. Although the scientific
      literature provides some answers, many issues of DVT prophylaxis are not
      completely addressed, especially with regard to the duration of prophylaxis. The
      most recent report from the American College of Chest Physicians Consensus
      Conference on Antithrombotic Therapy reconfirms the recommendations offered from
      previous consensus groups on the importance of establishing and applying a
      universal protocol for the prevention of DVT in orthopedic surgery.

PMID- 8856785
TI  - Physician practices in the prevention of deep vein thrombosis: the MassPRO DVT
      Study.
AB  - Numerous well-designed clinical trials have demonstrated that prophylaxis reduces
      the incidence of acute deep vein thrombosis (DVT) in high-risk surgical patients
      by two-thirds, with a corresponding reduction in mortality from pulmonary
      embolism. However, studies of clinical practices suggest that DVT prophylaxis is
      underused-for example, only 39% of high-risk surgical patients in 16 central
      Massachusetts hospitals were administered DVT prophylaxis in 1986. Subsequently,
      an intensive educational initiative was launched to improve utilization of DVT
      prophylaxis. Although some improvement was reported, the level of use was not
      optimal. The Massachusetts Peer Review Organization (MassPRO) DVT study was
      designed to gather data on recent practice patterns among Massachusetts surgeons
      and determine the need for additional educational and quality assurance efforts.
      The results indicate that there is broad compliance among orthopedic surgeons
      with consensus recommendations for the use of DVT prophylaxis. Nearly all
      patients who undergo total hip replacement in Massachusetts are protected from
      DVT by one or more methods of prophylaxis. These data suggest that the ongoing
      efforts to improve the use of DVT prophylaxis in Massachusetts since 1986 have
      come to fruition, at least with respect to total hip replacement.

PMID- 8856786
TI  - Implementation of guidelines for prevention of deep vein thrombosis in a managed
      care environment.
AB  - Implementation strategies are key factors in determining the overall success of
      clinical guidelines. They are important for changing physician practices and
      expected to result in clinical improvement or cost savings. Within an
      organization, the method of implementation should be a major component of the
      development of the guideline itself. In a group practice system, clinical
      guidelines must be clear and provide numeric thresholds or explicit criteria for
      decision points and subsequent action. Assessing the overall impact of a clinical
      practice guideline provides excellent feedback in determining whether goals are
      being met and provides guidance for fine-tuning strategic approaches. With regard
      to the prevention of deep vein thrombosis (DVT) monitoring, the overall results
      of a clinical practice guideline would assess guideline compliance, complications
      of the guideline interventions, as well as the incidence of DVT, pulmonary
      embolism, hospital readmissions, and mortality.

PMID- 8856787
TI  - Post-discharge prevention of deep vein thrombosis following total joint
      replacement.
AB  - Recent prospective studies demonstrate that the peak incidence of deep vein
      thrombosis (DVT) occurs on the fifth postoperative day. If the patient is to be
      discharged from an acute care facility on day 3 through 6, then the patient will
      be removed from direct supervision by professionals-frequently observing the
      patient in an acute care hospital during the high-risk period for the development
      of DVT or pulmonary embolism. In addition, the period of vulnerability for the
      development of thromboembolic disease in this group of patients appears to occur
      for an extended period of time, eg, 3 months. This change in practice has altered
      the surgeon's approach to the selection of agents for the prevention of
      thromboembolic complications. Most surgeons wish to administer an agent in the
      acute care setting that can be continued after the patient is discharged to the
      rehabilitation facility, subacute care facility, or home. This information
      reflects the belief of most orthopedic surgeons that prophylactic therapy should
      be continued beyond the time frame in which the patient is confined to the acute
      care facility. Although progress has been made in identifying effective
      prophylactic agents, questions remain as to the appropriate duration of
      prophylaxis. Based upon available data, it would appear that prophylaxis against
      thromboembolic disorders should be continued until the patient is spending the
      majority of his or her day ambulating with or without external aides.

PMID- 8856788
TI  - Balancing the clinical outcomes and economics associated with thromboembolic
      prophylaxis.
AB  - The approach to the treatment of patients is being influenced by the movement
      towards integrating health care services. This trend presents several challenges
      to health care professionals as patients move through the cycles of wellness,
      prevention, acute treatment, and after-care. Consequently, the development of
      treatment guidelines based upon clinical and economic parameters is critical.
      Preventing thromboembolic complications is receiving a great deal of attention
      due to the tremendous medical and economic consequences of deep venous thrombosis
      and pulmonary embolism. The early discharge of patients from acute surgical and
      medical facilities is increasing the need to consider outpatient prophylaxis.
      Pharmacoeconomic modeling demonstrates that enoxaparin may be more cost-effective
      than warfarin for outpatient prophylaxis when used for 3 weeks or less. The
      requirement of a subcutaneous injection of enoxaparin is not a detraction to this
      recommendation. Patient self-medication is a common practice and is growing in
      prevalence. Patients are eager to learn about their illnesses and treatment
      options as a result of their attitudes regarding empowerment and responsibility
      for their own health care.

PMID- 8856789
TI  - Severe stealth virus encephalopathy following chronic-fatigue-syndrome-like
      illness: clinical and histopathological features.
AB  - The clinical histories and brain biopsy findings of 3 patients with severe
      stealth virus encephalopathy are reviewed. The patients initially developed
      symptoms consistent with a chronic fatigue syndrome. One patient has remained in
      a vegetative state for several years, while the other 2 patients have shown
      significant, although incomplete, recovery. Histological and electron-microscopic
      studies revealed vacuolated cells with distorted nuclei and various cytoplasmic
      inclusions suggestive of incomplete viral expression. There was no significant
      inflammatory response. Viral cultures provided further evidence of stealth viral
      infections occurring in these patients.

PMID- 8856790
TI  - Genetic instability and fragmentation of a stealth viral genome.
AB  - Partial sequencing was performed on cloned DNA obtained from cultures of a
      stealth virus isolated from a patient with the chronic fatigue syndrome. The
      results extend earlier findings showing regions of homology to cytomegalovirus
      (CMV). Although the virus is much more closely related to simian CMV than to
      human CMV, many of the cloned viral segments could be aligned with the human CMV
      genome. The aggregate size of the aligned segments exceeds 100 kilobase pairs
      (kbp). Undigested viral DNA has a mobility in agarose gel electrophoresis
      corresponding to approximately 20 kbp. The virus, therefore, apparently exists in
      multiple fragments. Considerable sequence variation exists between individual
      clones which overlap to similar regions of the human CMV genome. The fragmented
      genome and sequence microheterogeneity suggest that both the processivity and the
      fidelity of replication of the viral genome are defective. An unstable viral
      genome may provide a potential mechanism of recovery from stealth viral illness.

PMID- 8856791
TI  - Chemical characterization of peroxidized low-density lipoprotein in plasma and
      aortic atheroma.
AB  - Hydroperoxidized cholesteryl linoleate (HPO-CL, spot X1) was produced by
      peroxidation of normal LDL isolated from plasma of healthy persons. Spot X
      stained on thin-layer chromatography plate (silica 60) between triglycerides and
      free fatty acids. The solvent mixture used consisted of petroleum ether 75, ethyl
      ether 25, and acetic acid 1. Spot X1 of plasma from healthy subjects stained
      slightly. It was also identified in plasma LDL of patients with atherosclerotic
      diseases, and in total lipids extracted from aortic atheroma obtained at autopsy.
      Whereas spot X1 obtained from plasma LDL of patients with atherosclerotic
      diseases consisted of HPO-CL, spot X1 obtained from aortic atheroma was reduced
      HPO-CL (hydroxide CL). Spot X1 of obtained from aortic atheroma was reduced HPO
      CL (hydroxide CL). Spot X1 of aortic atheroma did not react to p
      methoxydiphenylpyrenylphosphine (MP3)-an agent which shows only positive reaction
      to hydroperoxide chemical structures-although spot X1 of plasma LDL from
      atherosclerotic diseases reacted positively to MP3. Moreover, spot X1 obtained
      from aortic atheroma showed the same Rf value as that of the reduced HPO-CL. The
      IR profile of spot X1 obtained from aortic atheroma was similar to that of
      hydroxide CL, although the IR profiled HPO-CL was similar to that obtained from
      plasma LDL of atherosclerotic patients. In addition, HPO-CL was not recognized in
      the LDL fraction with clathrin-coated pits from aortic atheroma.

PMID- 8856792
TI  - Effects of unsaturated fatty acids on expression of early response genes in human
      T lymphocytes.
AB  - Administration of gamma-linolenic acid, which is converted rapidly to dihomo
      gamma-linolenic acid (DGLA), reduces joint swelling and tenderness in patients
      with rheumatoid arthritis. Joint tissue inflammation in patients with rheumatoid
      arthritis is due in part to activation of T lymphocytes. DGLA suppresses T cell
      activation and production of interleukin-2 (IL-2). The protooncogenes c-myc and c
      fos are early response genes which are critical to regulation of T cell
      proliferation. We therefore examined the effects of gamma-linolenic acid and
      other unsaturated fatty acids on c-myc and c-fos expression by means of the
      polymerase chain reaction and Northern blotting. IL-2 production by the human T
      cell line Jurkat is dependent on a fall in mRNA for c-myc and a rise in mRNA for
      c-fos. The data presented here indicate that reduction of steady-state levels of
      mRNA for c-myc and rises in steady-state levels of mRNA for c-fos are both
      reduced markedly in cells incubated with DGLA. Cells incubated with arachidonic
      acid, eicosapentaenoic acid or oleic acid exhibit more modest changes in
      expression of these early response genes.

PMID- 8856793
TI  - The diverse pathogenic potential of anti-DNA antibodies from various sources to
      induce experimental systemic lupus erythematosus.
AB  - It has previously been shown that immunization with pathogenic anti-DNA idiotypes
      (Ids; e.g. 16/6 Id) leads to the induction of experimental system lupus
      erythematosus (SLF) in naive mice. The disease is characterized by serological
      (e.g. anti-double-strand DNA), clinical (elevation of erythrocyte sedimentation
      rate, leukopenia and proteinuria) and histological (immune complex deposition in
      kidneys) parameters. To determine whether the 16/6 Id carrying anti-DNA
      antibodies has unique pathogenic ability, in the current study we have employed
      diverse sources of anti-DNA antibodies to induce experimental SLE. An IgM anti
      DNA antibody lacking the 16/6 Id was able to induce the production of the
      serological markers of experimental SLE, but not the clinico-histological
      findings. Furthermore, an IgA anti-DNA (16/6 Id derived from the serum of a
      patient with celiac disease was very effective in inducing the whole presentation
      of experimental SLE. Other anti-DNA antibodies failed to induce the autoimmune
      condition. Combined with our previous experience, the current study points to the
      diverse potential of various anti-DNA antibodies to induce SLE. The 16/6 Id is
      only one of a list of the potent pathogenic anti-DNA Ids. These facts may explain
      in part the diversity of clinical presentations of SLE, including asymptomatic
      subjects who carry high serum titers of anti-DNA antibodies.

PMID- 8856794
TI  - Increased applied pressure enhances the uptake of IgG complexes by macrophages.
AB  - Increased pressure, as may occur with hypertension, may alter cellular function
      by inducing repetitive mechanical strain. However, increased pressure itself may
      directly alter cellular function independent of stretching of cells. We undertook
      the present study to determine whether increased applied pressure could alter
      uptake of IgG complexes by macrophages. Increased pressure was applied to
      confluent macrophages grown on plastic culture plates using a pressure chamber
      apparatus kept inside the incubator at 37 degrees C and pressure regulated using
      a rotator pump and adjustable outlet valve. Macrophages that were subjected to
      increased pressure were found to have a significantly greater uptake of IgG
      complexes in a dose-dependent manner. The effect of increased pressure could be
      abrogated by carrying out experiments in calcium-free medium while this exerted
      no effect on uptake by macrophages under control conditions. Increased uptake of
      IgG complexes by macrophages subjected to increased applied pressure could also
      be attenuated by incubation with the calcium channel blockers amlodipine and
      cinnarizine. To determine whether the effect of increased pressure was related to
      the plastic substrate on which the cells are grown, cells were also seeded onto
      type I collagen gels and uptake of IgG complexes was measured. Uptake by
      macrophages on the type I collagen substrate was significantly enhanced with
      increased applied pressure compared to control (p < 0.01). These studies
      demonstrate that exposure of macrophages to increased pressure enhances their
      uptake of IgG complexes via a mechanism that appears to involve an increase in
      intracellular calcium. This effect might play a role in some of the consequences
      of systemic arterial and glomerular capillary hypertension.

PMID- 8856795
TI  - Relevance of ICAM-1 to alcoholic liver cirrhosis.
AB  - An elevated serum concentration of soluble intercellular adhesion molecule-1
      (sICAM-1) was observed in patients with alcoholic liver cirrhosis in strong
      correlation with the current activity of the liver disease and the history of
      alcohol consumption. Circulating ICAM-1 levels were significantly elevated in the
      sera of all of 25 patients (1,400 +/- 850 ng/ml) compared with normal healthy
      subjects. The highest levels of sICAM-1 (2,650 +/- 560 ng/ml) were measured in
      those patients who suffered from superimposed acute alcoholic hepatitis (SAH).
      Regularly drinking cirrhotic patients without SAH also exhibited significantly
      higher results than those who had stopped drinking. The serum ICAM-1
      concentration showed a negative correlation with the duration of abstinence. No
      elevated sICAM-1 was found in ascitic fluid of cirrhotic patients, which tends to
      discount a significant intraperitoneal production of this molecule. flow
      cytometric analysis revealed an increased expression of ICAM-1 molecules on
      peripheral blood monocytes of cirrhotic patients. Proliferating bile ducts and
      parenchymal cells of cirrhotic livers displayed a positive ICAM-1
      immunohistochemical reaction in 3 autopsy cases. It is concluded that the
      elevated levels of sICAM-1 in the serum of patients with alcoholic liver diseases
      may provide useful diagnostic or prognostic information. However, determination
      of the exact source of circulating ICAM-1 in patients with alcoholic cirrhosis
      still demands further investigations.

PMID- 8856796
TI  - HIV-1-related mechanisms of suppression of CD34+ hematopoietic progenitors.
AB  - Peripheral blood cytopenias and bone marrow abnormalities are frequently observed
      in HIV-1-seropositive subjects. Two major mechanisms have been proposed to
      explain the hematopoietic failure often observed in patients with advanced HIV-1
      disease: (i) infection of cells composing the bone marrow microenvironment with a
      deranged production of hematopoietic growth factors; (ii) direct suppression of
      hematopoietic progenitor cells mediated by HIV-1 virions and/or viral proteins.
      In vivo and in vitro experimental evidence supports a combination of both
      mechanisms. In fact, it has been shown that: (i) infection with HIV-1 and/or
      exposure of bone marrow accessory cells to envelope glycoprotein 120 (env gp 120)
      increases the production of inhibitory cytokines such as tumor necrosis factor
      alpha; (ii) a subset of CD34+ hematopoietic progenitor cells co-expresses the CD4
      antigen and may be infected in vivo with HIV-1; (iii) HIV-1 virions or immune
      complexes containing env gp 120 are able to induce apoptosis of uninfected CD34+
      hematopoietic progenitors. This last inhibitory effect appears to be mediated by
      the upregulation of transforming growth factor beta 1, which is endogenously
      produced by hematopoietic progenitors. Both the load and the biological
      characteristics of the virus play an important role in causing these suppressive
      effects, since different HIV-1 isolates display varying abilities to suppress
      hematopoiesis, and some isolates are not cytopathic at all.

PMID- 8856797
TI  - Effect of age, height, and prechallenge respiratory resistance on bronchial
      hyperresponsiveness in childhood asthma using the forced oscillation technique.
AB  - To evaluate the effects of age, height and prechallenge respiratory system
      resistance (Rrs) on bronchial responsiveness to methacholine inhalation (BRm) as
      measured by the oscillation technique in children with mild asthma, we studied
      BRm in 92 atopic children aged from 8 to 13 years (mean +/- SD, 10.5 +/- 1.7
      years). Inhalation challenge was performed by administering progressively
      doubling doses of methacholine, until a twofold increase in Rrs from baseline had
      been reached. The minimum cumulative dose of methacholine (Dmin) at which Rrs
      deviated from baseline was identified by the point of deflection of the
      continuously recorded Rrs tracing. The Dmin represented the amount of
      methacholine which elicited BRm. By using single-regression analysis, height was
      negatively correlated with Rrs (p < 0.001). Height was positively and Rrs was
      negatively correlated with age (p < 0.001 and p < 0.001, respectively).
      Furthermore, height and age were correlated with Dmin (p < 0.001 and p < 0.001,
      respectively), but prechallenge Rrs was not correlated with Dmin (p > 0.1). To
      minimize the effect of height and prechallenge Rrs on BRm, the relationships
      between Dmin and age was studied in a subgroup with a narrow range of heights
      (135-155 cm, n = 32), and a narrow range of prechallenge Rrs (5.0-6.9 cmH2 O/L/s,
      n = 42); there remained a statistically significant correlation between Dmin and
      age in the groups with comparable heights (p = 0.026) and Rrs (p = 0.003). These
      data suggest that the BHR in childhood asthma may be affected by height and age
      when measured by the oscillation technique. Considering the many advantages of
      the oscillation method, this technique may be very suitable for measuring BHR in
      childhood asthma.

PMID- 8856798
TI  - Respiratory system reactance as an indicator of the intrathoracic airway response
      to methacholine in children.
AB  - The upper airways may contribute to increases in airway resistance in response to
      a bronchial challenge, and thus decrease the specificity of such challenge tests
      to diagnose airway hyperresponsiveness when forced oscillation techniques are
      used to evaluate changes in respiratory system resistance (Rrs). A concomitent
      decrease in respiratory system reactance (Xrs) may indicate a change in the
      intrathoracic airways and/or lung parenchyma, provided that extrathoracic airway
      wall motion is prevented. To test the value of Xrs in the evaluation of bronchial
      hyperresponsiveness, we studied the respiratory impedance response to
      methacholine in 38 children with a history of asthma (aged 6-14.5 years), and
      compared the results to changes in the forced expiratory volume in one second
      (FEV1). Rrs and Xrs were measured by the forced oscillation technique with
      pseudorandom (11 subjects) or sinusoidal (27 subjects) pressure variations
      applied around the child's head to minimize upper airway wall motion. Changes in
      Rrs and in Xrs at 12 Hz (Rrs12, Xrs 12) correlated significantly with changes in
      FEV1 (P < 0.005). A decrease in FEV1 > or = 20% was observed in 23 subjects. When
      these 23 subjects were compared with the 15 children who did not show significant
      changes in FEV1, the responding group had larger mean +/- SEM changes in Rrs
      (116.0 +/- 13.2% vs 60.4 +/- 11.4%, P < 0.006) and in Xrs (-2.1 +/- 0.4 hPa.s/L
      vs -0.9 +/- 0.3 hPa.s/L, P < 0.03) than the nonresponders. The receiver operating
      characteristics (ROC) curve analysis was used to assess the diagnostic value,
      i.e., specificity and sensitivity, of different levels of change in Rrs and Xrs,
      with reference to FEV1. The overall incidence of false results was similar for
      Rrs and Xrs. The optimum diagnostic value for Rrs was a 70% increase, which
      corresponded to a sensitivity of 87% and a specificity of 67%. For Xrs the
      optimum decision level was -1 hPa.s/L, corresponding to a sensitivity of 70% and
      a specificity of 80%. It is concluded that Xrs may improve the specificity of the
      forced oscillation technique in interpreting the airway response to methacholine.
      This may be of particular interest in young children unable to perform forced
      expirations.

PMID- 8856799
TI  - Transferrin modifies surfactant responsiveness in acute respiratory failure: role
      of iron-free transferrin as an antioxidant.
AB  - In respiratory failure, transferrin (TF) with variable iron saturation
      accumulates in the alveolar space. Binding free iron to TF may inhibit metal
      catalyzed formation of free radicals. The aim of this study was to evaluate
      whether the degree of the iron-saturation of TF influences the severity of
      respiratory failure and surfactant responsiveness. Surfactant deficiency and lung
      edema was induced in 42 paralyzed and ventilated young rabbits by bronchoalveolar
      lavage (BAL); 19 of these animals were preexposed to 100% O2 for 40 hours. The
      animals received (1) exogenous surfactant intratracheally (100 mg/kg in 4 ml/kg
      saline); (2) surfactant and Fe(3+)-TF (50 or 25 mg/kg); or (3) surfactant and
      iron-free TF (50 mg/kg). One hour after administration of TF, 13-25% of exogenous
      TF was recovered by BAL. Administration of Iron-free TF significantly decreased
      the iron saturation of TF in BAL. In acute respiratory failure induced by BAL,
      Fe(3+)-TF decreased the efficacy of exogenous surfactant in improving the gas
      exchange, and increased surfactant inhibition, while iron-free TF had no effect.
      By contrast, in respiratory failure induced by hyperoxia and BAL, iron-free TF
      improved the efficacy of exogenous surfactant, but Fe(2+)-TF had no effect. After
      administration of iron-free TF, surfactant isolated from BAL was more surface
      active than surfactant from BAL of the other hyperoxia-treated animals. In
      animals exposed to hyperoxia, treatment with iron-free TF decreased
      malondialdehyde content of BAL. We propose that low iron saturation of TF
      decreases oxidant stress and favors the recovery from respiratory failure.

PMID- 8856800
TI  - Study of interobserver reliability in clinical assessment of RSV lower
      respiratory illness: a Pediatric Investigators Collaborative Network for
      Infections in Canada (PICNIC) study.
AB  - Randomized trials of ribavirin therapy have used clinical scores to assess
      illness severity. Little information on agreement for these findings between
      observers has been published. We decided to determine interobserver agreement for
      (1) a history for apnea or respiratory failure; (2) assessment of cyanosis,
      respiratory rate, retractions, and oximetry; and (3) determination of reason for
      hospitalization (requirement for medications, supportive care, underlying
      illness, poor home environment). At eight centers 137 RSV-infected patients were
      assessed by two observers blinded to the assessments by others with no
      interventions made between assessments. Observations were categorized, and
      agreement was summarized as percentage of observed agreement, Pearson
      correlation, or as a kappa statistic. Observed agreement for a history of either
      apnea or a respiratory arrest was at least 90% at all centers, with seven of the
      eight centers in total agreement. At all centers except one, the agreement on the
      reason why the patient remained in hospital was at least 80%. The observed
      agreement for assessing cyanosis was at least 94% at all eight centers. The
      correlation coefficient for respiratory rate varied from 0.42 to 0.97 across
      centers. The kappa values for agreement beyond chance for retractions varied from
      0.05 to 1.00. The kappa values for oxygen saturation measures varied from 0.31 to
      0.70. Although not statistically significant, there appeared to be more variation
      as the time between assessments increased. In conclusion, agreement for
      historical findings and assessment of cyanosis was high. However, there was wide
      variation in agreement in the other assessments. Training to ensure consistent
      and reproducible assessment by different examiners will be necessary if these
      findings are to be used as outcome variables in clinical trials.

PMID- 8856801
TI  - Patient-triggered ventilation: a comparison of tidal volume and chestwall and
      abdominal motion as trigger signals.
AB  - Patient-triggered synchronized ventilation requires reliable and early detection
      of the infant's inspiratory effort. Several trigger methods have been developed
      that frequently lack the sensitivity to detect inspiration in small preterm
      infants (trigger failure), or show a high rate of breaths triggered by artifacts
      in the respiratory signal (autotrigger). The purpose of this study was to
      determine the effectiveness of the following trigger signals: abdominal movement
      sensed by a newly developed induction technique, chestwall motion detected by
      changes in transthoracic impedance, and tidal volume measured by anemometry at
      the endotracheal tube connector. Ten preterm infants (birth weight, 580-1,424 g;
      median weight, 943 g; study weight, 535-1,415 g; median weight, 838 g; gestation
      age, 26-32 weeks, median gestational age, 28 weeks, study age, 1-50 days, median
      study age, 11 days) were included in the study. A Sechrist SAVI ventilator was
      triggered by one of three signals: chestwall or abdominal movement, or tidal
      volume generated by the infants. Response time between beginning of inspiratory
      flow, the occurrence of the trigger signal (signal delay), and the onset of the
      triggered breath (trigger delay) were determined for each of the three signals.
      The signal response time was -13.5 msec (95% CI, -33 to -2 msec) for the
      abdominal movement signal, indicating that it started before inspiratory flow;
      0.0 msec for the volume signal; and 44.0 msec (95% CI, 29-73 msec) for the
      chestwall signal (P < 0.002); this long delay was secondary to chestwall
      distortion and a subsequent delay in outward ribcage movement in many infants.
      The trigger delay for the abdominal signal was 90.0 msec (95% CI, 55-104 msec),
      135.5 msec (95% CI: 82-186 msec) for the volume signal, and 176.5 msec (95% CI:
      165-232 msec) for the chestwall signal, indicating that there was a difference in
      the rise time of signal voltage between the three methods (P < 0.01). The rate of
      autotriggered breaths was 3.2% (95% CI, 0.3-9.3%) when using the abdominal
      signal, 0.55% (95% CI, 0.0-2.1%) for the tidal volume signal, and 11.25% (95% CI,
      0.5-27.8%) for the chestwall signal (P < 0.05). The incidence of trigger failure
      was low with all three signals and was not significantly different between the
      techniques. In summary, the chestwall signal had a long trigger delay and was
      highly susceptible to false triggering. It is, therefore, not a reliable trigger
      signal for synchronized mechanical ventilation in preterm infants. In contrast,
      tidal volume and abdominal movement signals had an acceptable trigger delay and a
      low rate of autotriggering, making them useful clinical trigger signals.

PMID- 8856802
TI  - Effect of leak around the endotracheal tube on measurements of pulmonary
      compliance and resistance during mechanical ventilation: a lung model study.
AB  - We studied the effect of leaks around the endotracheal tube (ETT) on the
      measurement of pulmonary mechanics during mechanical ventilation. We also
      evaluated the influence of different ventilator settings on the magnitude of
      leak. An adjustable leak was created at the end of the ETT in a lung model with
      constant compliance. Flow, tidal volume, and pressure changes were measured above
      and below the leak. Compliance (Ci) and resistance (Ri) during inspiration were
      determined by linear regression analysis (LRA) using the equation of motion and
      the Mead and Wittenberger method (MWM). The ventilatory change that influenced
      the degree of leak most was prolongation of inspiratory time (Ti). The presence
      of a leak around the ETT resulted in an overestimation of the Ci and Ri values,
      which was proportional to the size of the leak. This overestimation was also
      influenced by the method used to determine Ci and Ri. Because the contribution of
      the leak to the fidal volume progressively increases as inspiration continued,
      methods of analysis that depended mainly on measurement points at the end of
      inspiration showed a larger deviation from the true Ci and Ri values than methods
      mainly influenced by measurement points at the beginning of inspiration. Because
      of this, shortening of inspiration, or analysis of points at the beginning of
      inspiration reduces the error in the measurements of Ci and Ri when a leak is
      present. Breaths with a large leak should be excluded from any analysis of
      pulmonary mechanics.

PMID- 8856803
TI  - The role of corticosteroids in respiratory diseases of children.
AB  - Glucocorticosteroids are potent anti-inflammatory agents and have an important
      role in a variety of respiratory diseases. Although their exact mode of action is
      unknown, it is thought that they exert their effects by binding to cytoplasmic
      glucocorticoid receptors. In certain conditions, such as asthma, the value of
      steroids cannot be questioned, and inhaled steroids have revolutionized
      management. In other situations, such as interstitial lung disease, the true role
      of steroids is still to be defined. In the management of diseases such as
      tuberculosis, the use of steroids is solely based on anecdotal experience.

PMID- 8856804
TI  - Comparison of total resistive work of breathing in two generations of ventilators
      in an animal model.
AB  - Spontaneous breathing through an endotracheal tube and ventilator circuit is
      associated with an increased work of breathing (WOB). Recently, pediatric
      ventilators have introduced improved features to optimize patient-ventilator
      interactions. We performed an experiment utilizing an animal model to compare
      total resistive WOB of two widely used ventilators, the Siemens Servo Ventilator
      300 (SV300) with patient-optimized features, such as flow-triggering and rapid
      response time, and the Siemens 900C (S900C) without those features. A total of
      120 experiments of 10 minutes duration each were performed in 6 anesthetized,
      intubated lambs. In each experiment, the animal was randomized to either pressure
      support ventilation (PSV) of 5 cm H2O, or continuous positive airway pressure
      (CPAP) with 0 cmH2O end expiratory pressure (ZEEP) while supported by the SV300
      or the S900C. Each animal was used as its own control. WOB was measured with a
      Bicore monitoring device as WOB of the animal (WOBp), WOB of the ventilator
      (WOBv), and the pressure time product (PTP) for each breath during the
      experiment. Oxygen consumption (Vo2) of the animal was measured using breath-by
      breath gas analysis with a customized metabolic monitoring system. A Wilcoxon
      signed rank sum test was used for analysis. All comparisons between the
      ventilators for both CPAP and PSV showed a statistically significant difference
      (p < 0.001). WOBp was reduced by 47% during pressure support ventilation (PSV)
      and by 47% during CPAP when the SV300 was used compared to the S900C. We conclude
      that WOB is significantly lower in animals ventilated with the SV300 than with
      the S900C ventilator, and we speculate that ventilators with the features of the
      SV300 may offer advantages in ventilating pediatric patients.

PMID- 8856805
TI  - Idiopathic bronchiolitis obliterans organizing pneumonia (idiopathic BOOP) in
      childhood.
AB  - Idiopathic bronchiolitis obliterans organizing pneumonia (idiopathic BOOP) is a
      clinicopathological entity of unknown origin first described by Epler and
      colleagues in 1985. We report our findings from a study of two Japanese boys aged
      12 and 13 years with idiopathic BOOP. The patients showed no respiratory symptoms
      nor signs of infection. There was no history of exposure to noxious agents or
      medications in either case. Laboratory data, including hematological,
      biochemical, and immunological tests, were normal, and pulmonary function tests
      showed only a slight nonprogressive decrease from normal predicted values in
      vital capacity and diffusing capacity. Serial radiographs in both cases showed
      migration of patchy infiltrates. Fiberoptic bronchoscopy was performed for
      evaluation of eosinophilic pneumonia, but the bronchoalveolar lavage (BAL)
      revealed no increase in eosinophils and a decrease in CD4/CD8 ratio in the BAL
      fluid. Histopathological findings of transbronchial lung biopsy (TBLB) specimens
      were compatible with a diagnosis of BOOP. As neither case has shown clinical
      abnormalities apart from migratory patchy infiltrates on chest radiographs, both
      patients have been observed without drug therapy for 3-4 years.

PMID- 8856806
TI  - Blood pressure and flow rate in the giraffe jugular vein.
AB  - Experimental measurements in the jugular veins of upright giraffes have shown
      that the internal pressure is somewhat above atmospheric and increases with
      height above the heart. A simple model of steady viscous flow in an inverted U
      tube shows that these observations are inconsistent with a model in which the
      blood vessels in the head and neck are effectively rigid and the system resembles
      a siphon. Instead, the observations indicate that the veins are collapsed and
      have a high resistance to flow. However, laboratory experiments with collapsible
      drain tubing in place of the down arm of the U-tube show internal pressure to be
      exactly atmospheric and uniform with height. A model of viscous flow in a
      collapsible tube with non-uniform properties is used to suggest that the observed
      pressure distribution may be a consequence of the intrinsic cross-sectional area
      and/or compliance of the veins increasing with distance towards the heart, or the
      external, tissue pressure falling. Finally, the effect of fluid inertia on steady
      flow in vertical collapsible tubes with uniform intrinsic properties is analysed,
      and it is shown that a phenomenon of flow limitation is theoretically possible,
      in which the supercritical flow in the collapsed vein cannot return to the
      presumably subcritical flow in the open vena cava, even with the help of an
      'elastic jump', if the flow rate is too large. The computed critical flow-rate,
      of about 80 ml s-1, is about twice the flow-rate estimated to be present in the
      normal giraffe jugular vein. If there were circumstances in which flow limitation
      occurred in the jugular veins, it would mean that the cerebral blood flow would
      be limited by downstream conditions, not directly by local requirements.

PMID- 8856807
TI  - DNA, morphology and fossils: phylogeny and evolutionary rates of the gastropod
      genus Littorina.
AB  - Using data from the direct sequencing of fragments of three mitochondrial genes
      (12S and 16S ribosomal RNA, and cytochrome-b; total length 1469 b.p.) we have
      reconstructed a gene phylogeny for all 19 living species of the gastropod genus
      Littorina. Members of the closely related genera Nodilittorina, Littoraria and
      Mainwaringia have been used as outgroups, and it appears that Littorina is
      monophyletic. An earlier morphological phylogeny has been revised, and its
      topology found to be almost entirely consistent with that from the molecular
      data. The fossil record is sparse, but likewise consistent. A consensus tree is
      presented, showing clear resolution of basal and terminal branches, and a central
      unresolved polychotomy. We have used fossil evidence and geological events to
      estimate the ages of some clades, and thus to calculate average rates of
      molecular evolution, which in turn provide approximate dates for all branches of
      the molecular phylogeny. The central polychotomy may be explained by a burst of
      rapid speciation in the northwestern Pacific during the Middle Miocene, perhaps
      driven by climatic fluctuation. Our results support the hypothesis that the two
      clades of Littorina in the northern Atlantic originated from Pacific ancestors
      which took part in the Pliocene trans-Arctic migration of marine organisms.

PMID- 8856808
TI  - Separating the environmental and genetic factors that may be causes of bovine
      spongiform encephalopathy.
AB  - The initial cause of the bovine spongiform encephalopathy (BSE) epidemic is
      generally accepted to have been the feeding of infected animal protein to cattle.
      The proportion of animals affected in any year in a particular herd has generally
      been low. This suggests either considerable variation in the extent of challenge
      of the individual animals or variation in their susceptibility to challenge or
      both. There is known to be genetic variation in susceptibility in other
      spongiform encephalopathies, such as scrapie in sheep. However, earlier
      indications that there may be associations between the incidence of BSE in cattle
      and polymorphisms and mutations in the PrP gene have not been confirmed (Hunter
      et al. 1994). Here, we attempt to model the likely extent of challenge of the
      individual animals in five Holstein Friesian pedigree herds and also the
      distribution of incubation times to the date of clinical onset. By studying the
      incidence of the disease in related animals we first found that single locus
      genetic models fitted the data much better than a non-genetic model. This was the
      first statistical evidence found of genetic variation in susceptibility to BSE. A
      check on the model in which individual animals were randomly allocated to
      'parents' showed that the result was due to the lack of allowance in the non
      genetic model for those animals insufficiently challenged or, for non-genetic
      reasons, resistant to their level of challenge. Thus there is still no evidence,
      molecular or statistical, for genetic variation in susceptibility. The importance
      of checking the attribution of genetic effects in complex models by the random
      allocation of progeny to parents is clear.

PMID- 8856810
TI  - Delirium. Advances in diagnosis, pathophysiology, and treatment.
AB  - This article discusses research in the areas of morbidity and mortality,
      epidemiologic risk factors, phenomenology, pathophysiology, and treatment of
      delirium. Delirium assessment instruments are reviewed. The neuropathophysiologic
      understanding of delirium is discussed in the context of important CNS neural
      circuitry. Pharmacologic treatments of delirium in adults and children are
      outlined, with particular emphasis on intravenous use of butyrophenone
      neuroleptics.

PMID- 8856809
TI  - Psychiatry and physician-assisted suicide.
AB  - The psychiatric literature on physician-assisted suicide is scant and almost
      universally opposed to legalization. This opposition stems from the traditional
      perspective of suicide as a symptom of mental illness and the tendency of
      psychiatrists to extend their view of suicide in the medically well to the
      terminally ill. This article examines the basis for and validity of this
      opposition and makes recommendations about the role of the psychiatrist in
      physician-assisted suicide.

PMID- 8856811
TI  - Consultation-liaison psychiatry in the managed care arena.
AB  - This article describes the history and current state of consultation-liaison
      psychiatry and managed care, the impact of managed care on consultation-liaison
      psychiatry, including service delivery and ethical issues, and recommendations
      for survival. The implications of managed health care delivery system
      reorganization for consultation-liaison psychiatry are important and offer
      challenges as well as opportunities for the field.

PMID- 8856812
TI  - Psychiatric interventions in the medically ill. Outcome and effectiveness
      research.
AB  - This article reviews the current status and emerging trends of outcome data from
      research studies of psychiatric and psychosocial interventions for mental
      disorders in patients in the general medical sector. Although data from such
      studies have had limited success to date in influencing health policy,
      legislators and administrators are increasingly likely to turn to outcome data to
      inform their decisions. The impact of psychiatric disorders, the recognition and
      treatment or referral of psychiatric-disordered patients by general medical
      practitioners, and the outcome results of psychiatric intervention programs are
      examined for both the inpatient and outpatient general medical sectors.

PMID- 8856814
TI  - New antidepressant drugs and the treatment of depression in the medically ill
      patient.
AB  - The advent of the SSRIs, venlafaxine, bupropion, and nefazodone, has greatly
      expanded pharmacologic treatment options for the depressed medically ill patient.
      Although the relatively benign side effects of these medications on cardiac
      conduction and blood pressure allow for more liberal use in the medically ill,
      these drugs nevertheless have different capacities for adverse drug interactions
      that must be considered. Nevertheless, such interactions can usually be avoided
      or managed by knowledgeable clinicians cognizant of the pharmacodynamic and
      pharmacokinetic principles outlined in this article.

PMID- 8856813
TI  - Psychiatric sequelae in seriously ill children and their families.
AB  - Going through a life-threatening illness as a child or adolescent is a
      tremendously stressful experience for the entire family. Although the majority of
      survivors do go on to adjust and function well, some have ongoing problems. These
      problems include evidence of posttraumatic stress, learning difficulties,
      depression, and anxiety. Their parents appear to be even more severely affected,
      possibly because they had a better appreciation at the time of the true dangers
      posed by the illness and the treatment. Little is yet known about their siblings,
      although it is clear that the acute stage of illness and treatment effects the
      entire family. Areas needing study include the long-term sequelae on siblings of
      survivors, as well as a better understanding of the precipitants and mediators of
      the problems noted in survivors and parents. Only then can interventions and
      preventative measures be undertaken and tested. Also needed is a better
      understanding of the impact of cultural differences on precipitants, mediators,
      and symptoms.

PMID- 8856815
TI  - Use of stimulants in the medically ill.
AB  - This article discusses the use of psychostimulants, such as dextroamphetamine,
      methylphenidate, and pemoline, in a variety of illnesses, including depression in
      the medically ill, cancer, HIV, and AIDS. The chemistry and pharmacology, side
      effects, drug interactions, dosing, and abuse potential also are reviewed.

PMID- 8856816
TI  - Chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized
      by chronic, disabling fatigue, impaired concentration, muscle pain, and other
      somatic symptoms. The conceptual difficulties associated with all medically
      unexplained illnesses contribute to the controversy surrounding CFS, which has
      centered around whether it is best regarded as a medical or as a psychiatric
      condition. Clinically, such an approach is not helpful, and current research
      suggests that both pathophysiologic changes and psychosocial factors are
      important. Pragmatic management based on a detailed assessment of the individual
      is outlined.

PMID- 8856817
TI  - Psychiatric aspects of rheumatology.
AB  - The rheumatic diseases pose significant and challenging problems for the
      consulting psychiatrist because of their multifaceted clinical features.
      Consideration must be given to the complexity of the social system in which the
      patient lives, the rheumatologist-patient relationship, the losses incurred by
      the illness, immunologic vulnerability to opportunistic infections, the effects
      of concurrent medical treatments (especially drug treatments), and any antecedent
      pathologic conditions. This article examines the clinical and treatment
      highlights of two representative rheumatologic diseases: rheumatoid arthritis and
      systemic lupus erythematosus.

PMID- 8856818
TI  - Advances in comprehensive pain management.
AB  - Chronic pain is a significant public health problem and frustrating for everyone
      affected by it. Psychiatrists should take an active role in the care of patients
      with chronic pain. They no longer should wait to make a psychiatric diagnosis by
      exclusion in the patient who has failed to respond to multiple treatments over a
      period of years. Recent advances in the treatment of chronic pain include the
      diagnosis and treatment of psychiatric comorbidity, the application of primary
      psychiatric treatments to chronic pain, and the development of interdisciplinary
      efforts to provide comprehensive health care to the patient suffering with
      chronic pain.

PMID- 8856819
TI  - Psychiatric aspects of cardiovascular disease.
AB  - The co-occurrence of psychiatric and cardiac disease in many patients exemplifies
      the complexity of psychosomatic medicine, with both psychosomatic and
      somatopsychic effects. Psychological factors including depression, anxiety, and
      hostility influence the development, clinical expression, and prognosis of
      coronary heart disease. Depression and anxiety are especially common problems
      complicating cardiac disease. The physician must approach the patient with an
      appreciation of the confounding aspects of diagnosis and a readiness to think
      flexibly about the nature of the problems encountered. SSRIs play an increasingly
      prominent role in psychopharmacotherapy of this population. Innovative treatments
      in cardiology, such as heart transplantation, defibrillators and mechanical
      ventricular assist devices are associated with characteristic psychiatric
      problems for which psychiatrists must devise treatment strategies.

PMID- 8856820
TI  - A phobia of the couch: a clinical study of psychoanalytic process.
AB  - Conversion from psychotherapy to psychoanalysis and the differences between the
      two have been the subject of discussion and controversy in recent years. The
      theoretical and technical questions that have been raised suffer from the lack of
      detailed clinical accounts that might help to elucidate the processes involved.
      The author presents a case of a woman whose refusal to use the couch for three
      years became a central organizing resistance and took on the structure of a
      phobia. It is argued that the case, rather than a conversion from psychotherapy
      to psychoanalysis, was one of psychoanalysis from the beginning, with the
      conflicts about the couch analyzed as are any other resistances.

PMID- 8856821
TI  - The perils of neutrality.
AB  - The concept of analytic neutrality is reviewed with respect to its utility as a
      technical guideline. Participation of an analyst's personal judgments and affects
      in clinical work is discussed in relation to differing conceptions of how
      learning takes place in analysis. The question of what actually protects a
      patient from being exploited by an analyst is considered. A case example is
      provided as a basis for discussion.

PMID- 8856822
TI  - The moth as an allusion to (symbol of?) mother.
AB  - The meanings of the image of the moth are examined. The use of the moth as both
      victim and predator, with allusive and symbolic reference to parent and child, is
      elucidated. My emphasis is on the equation of the moth by children with their
      intrapsychic registration of a destructive yet vulnerable parent (usually mother)
      whom the child both wants to destroy and feels it cannot live without. This
      simple thesis is made use of chiefly to explicate aspects of the life and works
      of the great American writer, Elizabeth Bishop.

PMID- 8856823
TI  - Love and illusion.
AB  - The interplay between idealization and disillusionment in the evolution of
      romantic love is examined. Idealization refers to the reawakening of conscious
      and unconscious fantasies that lovers project onto each other. Disillusionment
      refers to a change in perception that occurs when projections are not sustained.
      The optimal balance between idealization and disillusionment facilitates the
      deepening of intimacy in a process similar to the one Kohut describes in the
      development of self structure. Conversely, a great imbalance between idealization
      and disillusionment can lead to heartache. Works by Freud, Kernberg, and Kohut
      are discussed.

PMID- 8856824
TI  - Franz Kafka's The Trial: guilty or innocent?
AB  - Through an examination of The Trial by Kafka I attempt to show that the depiction
      of the Court apparatus is dynamically related to the commission of unconscious
      crimes of the type we encounter in our patients. To provide a context for the
      novel, I discuss Kafka's biography and some possible unconscious motivations. My
      goal is to show how the concept of a particular type of superego pressure can be
      used to understand the subtle irony in The Trial. Although Joseph K.'s behavior
      frequently involves oedipal crimes, there are many preoedipal themes that help
      account for his experience of the Court. I contrast this psychoanalytic
      understanding of K.'s guilt with that of literary critics who interpret The Trial
      as an allegory of guilt but who minimize the psychological dimensions.

PMID- 8856825
TI  - Diving the wreck: risk and injury in sport scuba diving.
AB  - This paper utilizes psychoanalytic theory to examine risk and injury in the case
      of a male deep sea diver. It examines the unconscious conflicts which appeared to
      fuel the diver's involvement in deep diving and to lead to a near fatal incident
      of decompression sickness. Particular attention is paid to the role of the
      diver's father in the evolution of the preoedipal and oedipal fantasies and
      conflicts which appear to be linked to the injury. The research is based on
      interviews with and fieldwork among recreational and deep divers.

PMID- 8856826
TI  - Samuel A. Guttman. 1914-1995.

PMID- 8856827
TI  - Tryptophan depletion and aggressive responding in healthy males.
AB  - In order to study the effect of decreasing plasma tryptophan levels on aggressive
      responding in a controlled laboratory setting, we administered two doses (25 g
      and 100 g) of a tryptophan-free amino acid mixture to ten healthy male subjects
      after 24 h of a low tryptophan diet. Subjects were screened for current or past
      psychiatric, or non-psychiatric medical illness. Aggressive responding on a free
      operant laboratory measure of aggression (the Point Subtraction Aggression
      Paradigm) and plasma tryptophan levels were measured before and after drinking
      the amino acid mixture. There was a significant increase in aggressive responding
      5 h after the 100 g mixture and a significant increase in aggressive responding 6
      h after the 25 g mixture compared to a baseline day when no drink was
      administered. There was also a significant decrease in plasma tryptophan at 5
      hours after ingestion compared to baseline for both doses of amino acid mixture.
      This study supports the hypothesis that tryptophan depletion increases aggressive
      responding in healthy males in a laboratory setting, probably by decreasing brain
      serotonin.

PMID- 8856828
TI  - Fear-potentiated startle response is remarkably similar in two laboratories.
AB  - The fear-potentiated startle response paradigm is used to investigate anxiolytic
      properties of drugs. The first objective of the present study was to further
      investigate the predictive validity of this paradigm. The anxiolytics
      chlordiazepoxide (2.5-10 mg/ kg IP) and oxazepam (1-10 mg/kg PO) and the putative
      anxiolytic flesinoxan (1-10 mg/kg PO) decreased startle potentiation dose
      dependently, indicating an anxiolytic effect. The antidepressant fluvoxamine (5
      20 mg/kg PO) did not affect startle potentiation. Ideally, anxiolytic drugs
      attenuate startle potentiation without affecting control startle levels, although
      some studies report altered control startle amplitudes. The second objective was
      to investigate whether different effects on control startle amplitudes are
      related to different startle devices. Therefore, the drugs were tested in two
      laboratories. Results showed no significant differences between laboratories,
      indicating that equipment is not a critical factor in the drug-induced alteration
      of control startle levels. In an additional experiment, it was shown that
      flesinoxan (10 mg/kg PO) did not affect strychnine-induced startle potentiation,
      supporting the idea that the attenuating effect of flesinoxan on the fear
      potentiated startle response is due to its anxiolytic properties. Thus, the fear
      potentiated startle response paradigm appears a valid and reliable model for
      anxiolytic properties of drugs.

PMID- 8856829
TI  - Naloxone effects on sucrose-motivated behavior.
AB  - The opioid system plays an important role in feeding. In general, opioid agonists
      typically increase feeding and opioid antagonists decrease feeding in non-food
      restricted animals. In food restricted animals the effects of these drugs are
      substantially reduced. Opioid antagonists have shown a marked effectiveness at
      reducing consumption of sweet foods. Explanations for this robust effect have
      typically focused on drug induced changes in taste, taste perception, or
      palatability. The current study relates the effects of the opioid antagonist
      naloxone on motivation to obtain different sucrose concentrations to the drug's
      effects on unrestricted sucrose solution consumption. Changes in motivation to
      respond were assessed under a progressive ratio reinforcement schedule (PR) which
      required increased response cost for each successive unit of sucrose solution.
      Motivation, as measured by the PR, increased as sucrose concentration increased
      and naloxone produced a dose-dependent decrease in motivation to respond for a
      given sucrose concentration. Thus, the effectiveness of naloxone was indirectly
      related to strength of the sucrose concentration. Under unrestricted access to
      sucrose solutions, naloxone reduced consumption greatest under the higher
      concentrations. The data suggest at least part of naloxone's effects on sweet
      tasting food may be mediated through endogenous opioid reward systems that are
      reflected in measures of motivation.

PMID- 8856830
TI  - Alprazolam, caffeine and their interaction: relating DRL performance to
      pharmacokinetics.
AB  - Three-hour sessions of differential reinforcement of low-rate behavior (DRL 45-s)
      in rats were used to investigate alprazolam, caffeine, and their interactions at
      the onset, peak and disappearance of serum alprazolam, while caffeine level
      remained constant. The dose-response curve (DRC) method of Poch permitted an
      extensive evaluation of the kind (additivity or independence) of interactions
      occurring in combined drug effects. The alprazolam and caffeine DRCs were used to
      derive theoretical additive and independent relations, and the observed combined
      effects compared to these functions. Behavior-time profiles of the combined
      effects were similarly compared. Serum alprazolam and caffeine concentrations
      correlated with their respective behavior-time profiles. No acute tolerance was
      observed either for the individual drugs or their combinations. Alprazolam was
      more potent than caffeine in disrupting DRL behavior. Because alprazolam is much
      shorter-lived (t1/2 = 32 min) than caffeine (t1/2 = 3 h) in rats, potency ratios
      between alprazolam and caffeine changed across session time (from 123 to 4),
      which determined the expression of the combined effects. Although the combined
      effects were not distinguishable in terms of additivity or independence in both
      the DRCs and in the behavior-time profiles, they showed neither synergism nor
      antagonism. The pharmacokinetics of alprazolam were not altered by caffeine, but
      those of caffeine were affected by alprazolam.

PMID- 8856831
TI  - Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid
      receptor mechanism.
AB  - The purpose of the present study was to investigate whether the cannabinoid and
      cholinergic systems impair working memory through a common mechanism. This
      hypothesis was tested by examining whether the cannabinoid antagonist SR141716A
      would ameliorate radial-arm performance deficits caused by either the naturally
      occurring cannabinoid, delta 9-THC, or scopolamine, a muscarinic antagonist. In
      addition, we evaluated whether the cholinesterase inhibitor, physostigmine, would
      prevent delta 9-THC-induced impairment of spatial memory. Finally, because the
      locomotor suppressive effects of cannabinoids may decrease radial arm choice
      accuracy independent of a direct effect on memory, we examined the impact of
      increasing the intertrial error on radial arm choice accuracy. As previously
      reported, delta 9-THC impaired maze performance (ED50 = 3.0 mg/kg). Increasing
      the intertrial interval from 5 s to 30 s resulted in a three-fold increase in the
      amount of time required to complete the maze without affecting choice accuracy.
      Importantly, SR141716A prevented delta 9-THC-induced deficits in radial-arm
      choice accuracy in a dose-dependent manner (AD50 = 2.4 mg/kg); however, the
      cannabinoid antagonist failed to improve the disruptive effects of scopolamine.
      Conversely, physostigmine failed to improve performance deficits produced by
      delta 9-THC. These data provide strong evidence that delta 9-THC impairs working
      memory through direct action at cannabinoid receptors. Moreover, these results
      suggest that scopolamine and delta 9-THC do not impair spatial memory in a common
      serial pathway, though they may converge on a third neurochemical system.

PMID- 8856832
TI  - Influence of training dose on nicotine discrimination in humans.
AB  - Non-human research indicates that drug discrimination results may depend largely
      on the specific training conditions, including initial training dose. It has
      recently been shown that humans can discriminate among different doses of
      nicotine delivered by nasal spray. In this study, we examined the influence of
      training dose on subsequent behavioral discrimination of a range of nicotine
      doses. Male (n = 17) and female smokers (n = 16) were randomly assigned to "low"
      (10 micrograms/kg) versus "high" (30 micrograms/kg) nicotine training dose groups
      and trained reliably to discriminate this dose from placebo (0) on day 1 (> or =
      80% correct identification). All but six subjects (four in low, two in high)
      learned this discrimination and continued on to day 2, in which both groups
      received 0, 5, 10, 20, and 30 micrograms/kg in ascending order (30 min between
      dosings) and were tested for generalization with their training dose using
      quantal and quantitative behavioral discrimination tasks. Subjective responses
      via traditional self-report measures were also assessed. Nicotine-appropriate
      responding on day 2 was significantly greater in low- versus high-dose groups,
      especially at 5 micrograms/kg. However, this difference due to training dose was
      seen more in women than in men. Discrimination behavior was associated with
      subjective effects of head rush in males, and with head rush and decline in urge
      to smoke in females. These results show that discriminative stimulus effects of
      nicotine are not fixed properties of the drug, but can be influenced by training
      conditions, and that effects associated with this discrimination may differ
      between men and women.

PMID- 8856833
TI  - The discriminative stimulus effects of tripelennamine in humans.
AB  - Twenty volunteers were trained to discriminate between 75 mg tripelennamine (TP)
      and placebo. During the first four sessions, the drugs were identified prior to
      ingestion by letter code. During the next six sessions, the procedure was the
      same except the capsules were not identified. At the end of the 3-h session,
      participants indicated which capsule they believed they received using the letter
      codes. When correct, they received a monetary bonus. If they were correct on five
      sessions, they entered the third phase which had ten additional training and 12
      test sessions. During tests, participants received capsules that contained other
      drugs, including diphenhydramine (50 and 75 mg), chlorpheniramine (4 and 6 mg),
      diazepam (5 and 10 mg), d-amphetamine (5 and 10 mg), as well as tripelennamine
      (25, 50 and 75 mg) and placebo. Thirteen participants learned the discrimination
      and nine entered the third phase. Except for placebo, most participants
      identified the test compounds as TP and labeled them as sedatives. TP produced
      significant changes on several subjective and physiological measures. The test
      compounds produced varied effects which were neither clearly dose-related nor
      related to the identification as TP or placebo. These results indicate that
      tripelennamine can function as a discriminative stimulus, but with little
      evidence of pharmacological specificity.

PMID- 8856834
TI  - Genetic differences in naloxone enhancement of ethanol-induced conditioned taste
      aversion.
AB  - The influence of the opioid system on acquisition of an ethanol-induced
      conditioned taste aversion was examined in alcohol-preferring and avoiding inbred
      strains of mice (C57BL/6J and DBA/2J). Fluid-deprived mice from each strain
      received either ethanol alone, naloxone alone, or both ethanol and naloxone
      immediately after access to a novel tasting fluid. Naloxone alone (1 or 3 mg/kg)
      did not induce a conditioned taste aversion in either strain of mice.
      Administration of ethanol (1.5 g/kg) to DBA/2J mice produced a moderate taste
      aversion that was not affected by co-administration of naloxone. Although ethanol
      administered alone (3 g/kg) did not cause a taste aversion in C57BL/6J mice, the
      combination of ethanol and the higher dose of naloxone produced a significant
      taste aversion that increased across trials. A second experiment addressed the
      possibility that naloxone failed to enhance the ethanol-induced condition taste
      aversion in DBA/2J mice due to a "floor" effect on consumption. A lower ethanol
      dose (1 g/kg) was given alone or in combination with naloxone (1 or 3 mg/kg).
      Again, ethanol produced a moderate conditioned taste aversion that was not
      potentiated by naloxone. Subsequent conditioning with a high ethanol dose
      produced further suppression of intake, confirming that naloxone's failure to
      enhance aversion on earlier trials was not due to a "floor" effect. These data
      demonstrate a strain specific interaction between the aversive effect of ethanol
      and naloxone. More specifically, the results indicate that blockade of opioid
      receptors enhances the aversive effect of ethanol in C57BL/6J but not DBA/2J
      mice, suggesting that genetically determined differences in the endogenous opioid
      system of alcohol-preferring mice may mitigate ethanol's aversive effect.

PMID- 8856835
TI  - Pavlovian conditioning of morphine hyperthermia: assessment of interstimulus
      interval and CS-US overlap.
AB  - The present study examined the effect of interstimulus interval on acquisition of
      conditioned thermal responses produced by trials in which a light/noise stimulus
      (CS) was repeatedly paired with infusion of morphine sulphate (US). Rats were
      implanted with a chronic intravenous catheter for drug delivery and a
      biotelemetry device for remote monitoring of core body temperature. In experiment
      1, different groups received morphine either 0.5 (group P0.5) or 15 min (group
      P15) after onset of the 15-min CS. A third group was exposed to an identical
      number of CS and US presentations but in an explicitly unpaired manner (group
      UP). After repeated exposure to morphine, all groups showed a more rapid rise in
      body temperature in response to drug infusion. Test presentations of CS alone
      revealed conditioned hyperthermic responses to CS in groups P0.5 and P15.
      However, the response of the P15 group was smaller than that of the P0.5 group,
      suggesting weaker conditioning at the longer interstimulus interval. The
      contribution of CS-US overlap to the diminished associative strength observed in
      the P15 group was assessed in experiment 2. Groups P0.5/15 and P0.5/30 received
      infusions of morphine 0.5 min after onset of a 15- or 30-min CS, respectively.
      Group P15/30 received morphine 15 min after onset of a 30 min CS, whereas group
      UP/30 received explicitly unpaired presentations of the US and a 30-min CS.
      Enhancement of the hyperthermic effect of morphine was observed in all groups
      after ten conditioning trials. Test presentations of the CS without drug revealed
      that all paired groups had acquired conditioned hyperthermic responses. These
      results support the conclusion that drug-induced conditioning can occur at
      relatively long interstimulus intervals when there is sufficient temporal overlap
      between the CS and unconditioned response evoked by the drug US.

PMID- 8856836
TI  - Improvement of memory in rodents by the selective CB1 cannabinoid receptor
      antagonist, SR 141716.
AB  - Social short-term memory in rodents is based on the recognition of a juvenile by
      an adult conspecific when the juvenile is presented on two successive occasions.
      Cannabimimetics are claimed to induce memory deficits in both humans and animals.
      In the brain, they mainly bind to CB1 receptors for which anandamide is a
      purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors,
      dose-dependently reverses biochemical and pharmacological effects of
      cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal
      long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases
      arousal when given alone. The present experiments study the ability of SR 141716
      (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social
      recognition test in rodents. SR 141716 improved social recognition in a long
      intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it
      antagonized the memory disturbance elicited by retroactive inhibition.
      Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect.
      Moreover, SR 141716 reduced memory deficit in aged rats (0.03-0.1 mg/kg) and mice
      (0.3-1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity
      which is not mediated by CB1 receptors, the results strongly support the concept
      that blockade of CB1 receptors plays an important role in consolidation of short
      term memory in rodents and suggest there may be a role for an endogenous
      cannabinoid agonist tone (anandaminergic) in forgetting.

PMID- 8856837
TI  - Anxiolytic properties of endogenously occurring pregnanediols in two rodent
      models of anxiety.
AB  - Certain endogenously occurring 3 alpha-hydroxylated, 5-reduced pregnane steroids
      act at a specific site on the GABAA receptor complex (GRC) to modulate the
      effects of GABA at its receptor. Modulators that potentiate GABA at the GABAA
      receptor often possess anxiolytic properties. The anxiolytic potential of four 5
      reduced, 3 alpha, 20-pregnanediols, differing only in the stereochemical
      orientation of the steroid A-ring and the 20-hydroxyl group, were tested in the
      Vogel test following intracerebroventricular (ICV) administration. The effects of
      these pregnanediols were compared to those of their 20-ketone analogues, 3 alpha
      hydroxy-5 alpha-pregnan-20-one (3 alpha, 5 alpha-P) and 3 alpha-hydroxy-5 beta
      pregnan-20-one (3 alpha, 5 beta-P). All four pregnanediols tested significantly
      enhanced punished drinking at doses ranging from 10 to 60 micrograms. The rank
      order of potency based on the minimum effective dose (MED) observed was 5 alpha
      pregnan-3 alpha,20 alpha-diol = 5 beta-pregnan-3 alpha,20 alpha-diol > 5 beta
      pregnan-3 alpha,20 beta-diol > 5 alpha-pregnan-3 alpha, 20 beta-diol. 3 alpha,5
      beta-P and 3 alpha,5 alpha-P enhanced punished responding when administered at
      2.5 and 5 micrograms, respectively. 3 beta,5 alpha-P which is inactive at the GRC
      was also inactive (up to 100 micrograms) in the Vogel test. The benzodiazepine
      control diazepam was efficacious when administered at 2.5 micrograms. 5 alpha
      Pregnan-3 alpha,20 alpha-diol was further tested in the mouse elevated plus-maze
      model following systemic administration where it was found to be active in a dose
      range of 10-40 mg/kg IP. These results raise the possibility that in addition to
      3 alpha,5 alpha-P and 3 alpha,5 beta-P, some of their endogenously occurring
      pregnanediol metabolites may also influence physiological processes related to
      anxiety via the GRC.

PMID- 8856838
TI  - Low dose melatonin improves sleep in healthy middle-aged subjects.
AB  - We studied the effects of single evening doses of melatonin (0.3 mg and 1.0 mg
      orally) on polysomnographically measured sleep in 15 healthy middle-aged
      volunteers, using a placebo-controlled, double-blind, cross-over design. Compared
      to placebo, the 1.0 mg dose of melatonin significantly increased Actual Sleep
      Time, Sleep Efficiency, non-REM Sleep and REM Sleep Latency. These data are
      consistent with the hypothesis that low dose melatonin has hypnotic effects in
      humans. It is possible that administered melatonin may have a role to play in the
      treatment of sleep disorders.

PMID- 8856839
TI  - Agonizing over antagonizing: what do benzodiazepine receptor antagonists
      demonstrate?

PMID- 8856840
TI  - The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia
      reperfusion injury.
AB  - Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and
      superoxide, which reacts with proteins, lipids, and DNA under conditions of
      inflammation and shock. Here we overview the role of peroxynitrite in circulatory
      shock and inflammation. Immunohistochemical and biochemical evidence demonstrate
      production of peroxynitrite in endotoxic and hemorrhagic shock, chronic bowel
      inflammation, and in various forms of ischemia-reperfusion injury. The reactivity
      and decomposition of peroxynitrite is determined by the chemical environment, and
      the ratio of superoxide versus NO. Peroxynitrite can initiate toxic oxidative
      reactions in vitro and in vivo. Initiation of lipid peroxidation, direct
      inhibition of mitochondrial respiratory chain enzymes, inactivation of
      glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATP-ase
      activity, inactivation of membrane sodium channels, and other oxidative protein
      modifications contribute to the cytotoxic effect of peroxynitrite. In addition,
      peroxynitrite is a potent trigger of DNA strand breakage, with subsequent
      activation of the nuclear enzyme poly-ADP ribosyl synthetase, with eventual
      severe energy depletion of the cells. Pharmacological evidence suggests that the
      peroxynitrite-poly-ADP ribosyl synthetase pathway importantly contributes to the
      cellular injury in endotoxic shock, inflammatory pancreatic islet cell
      destruction, and central nervous system ischemia. The proposal that peroxynitrite
      is a major cytotoxic mediator would change the interpretation of previous data on
      the effects of NO donors, NO synthase inhibitors, and superoxide neutralizing
      strategies in shock and inflammation.

PMID- 8856841
TI  - Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat
      skeletal muscle: effects on plasma lactate.
AB  - The pyruvate dehydrogenase (PDH) complex undergoes reversible phosphorylation
      catalyzed by a PDH kinase (inactivating) and a PDH phosphatase (activating). In
      skeletal muscle, a decreased proportion of PDH complex in the active,
      nonphosphorylated form (PDHa) limits glucose oxidation and promotes the
      conversion of pyruvate to lactate. Increased lactate formation with the
      accompanying hyperlactatemia is a frequent metabolic complication of sepsis. The
      time course for inactivation of the PDH complex in skeletal muscle during sepsis
      was contrasted with changes in PDHa during sterile inflammation 3,7, or 14 days
      following the implantation of the foreign body nidus. Total PDH complex activity
      was not altered in any of the conditions examined. Sepsis, but not sterile
      inflammation, caused a reduction in the muscle PDHa measured 3 or 7 days
      following induction of sepsis. The inhibition of the muscle PDHa during sepsis
      was associated with a sustained hyperlactatemia. PDH kinase activity measured in
      extracts of mitochondria was enhanced twofold during this period. Fourteen days
      after induction of sepsis, there were no differences in the PDHa or plasma
      lactate concentrations in septic rats compared with either control or sterile
      inflammation. Furthermore, the PDH kinase activity was decreased to values
      observed in control values. The results are consistent with the hypothesis that a
      reduced PDHa in skeletal muscle during sepsis is responsible, in part, for the
      hyperlactatemia characteristic of septic hypermetabolism. Furthermore, the
      results provide evidence that the decrease in PDHa results from a stable
      stimulation of PDH kinase activity.

PMID- 8856842
TI  - Effects of the angiotensin converting enzyme inhibitor enalapril on bacterial
      translocation after thermal injury and bacterial challenge.
AB  - Burn injury and sepsis produce acute gastrointestinal derangements that may
      predispose patients to bacterial translocation. We studied the effects of
      enalapril, an angiotensin converting enzyme inhibitor (ACEI), on gastrointestinal
      anatomic alterations, bacterial translocation, and related mortality during gut
      derived sepsis in burned mice that had received a prior bacterial challenge.
      BALB/c mice (n = 111) were treated with enalapril 10 or 1 mg/kg body weight or
      sterile saline as control twice daily for 3 days. They were then gavaged with
      10(a)111 in radiolabeled or unlabeled Escherichia coli and given a 20% total body
      surface area (TBSA) burn injury. Animals gavaged with unlabeled bacteria were
      observed for survival (n = 60). Survival was significantly higher in the group
      receiving enalapril 10 mg/Kg compared with control (75% vs. 10%). Mice treated
      with enalapril maintained small intestine weight, measured 4 h postburn, and
      ileal mucosal height was preserved, whereas burned untreated animals lost
      intestinal weight and mucosal height. Bacterial translocation was decreased in
      mice treated with enalapril, but killing was unaffected. This study suggests that
      treatment with enalapril positively affects the outcome in gut-derived sepsis by
      ameliorating gastrointestinal structural and functional damage and decreasing
      bacterial translocation.

PMID- 8856843
TI  - Calcium signaling restitution prevents T-cell proliferative suppression by
      prostaglandin E2.
AB  - Previous studies from our laboratory have implicated a role for Ca2+ in
      prostaglandin E2 (PGE2)-induced suppression in T-cell proliferation during
      sepsis. The present study further elucidated the mechanism of PGE2-induced
      suppression in T-cell proliferation. We assessed whether prevention of the
      suppression in Ca2+ mobilization in PGE2-treated T-cells would restore
      proliferation. Rat splenic T-cell Ca2+ mobilization and proliferation were
      measured after stimulation of cells with concanavalin A (Con A) employing Fura-2
      spectroscopy and cellular [3H]thymidine uptake techniques, respectively. PGE2 and
      other agents that directly up-regulate the PGE2-mediated cell signaling events
      (e.g., cholera toxin and forskolin), substantially suppressed both Con A-induced
      proliferation (p < .01) and Ca2+ mobilization in T-cells (p < .01). When
      stimulated with Con A plus ionomycin, [Ca2+]i in PGE2 treated T-cells (395 +/-
      21, nM) was not significantly different (p > .05) from that observed in Con A
      stimulated T-cells without the PGE2 exposure (351 +/- 8.6). The stimulation of
      PGE2-treated T-cells with ionomycin and Con A also significantly (p < .025), if
      not completely, prevented the PGE2-induced suppression in T-cell proliferation.
      These results suggest that the cross-talk between the TCR- and PGE2-mediated
      signaling in T-cells negatively modulates the TCR signals at the Ca2+
      mobilization step and/or earlier to it.

PMID- 8856844
TI  - Effect of endotoxin-enhanced hepatic reperfusion injury on endothelium-dependent
      relaxation in rat aorta.
AB  - We have investigated endothelial function in a two-hit model of multiple organ
      failure. Male Fischer rats were subjected to 20 min of partial hepatic ischemia
      followed by reperfusion and administration of .5 mg/kg Salmonella enteritidis
      endotoxin at 30 min of reperfusion. After either 4 or 24 h of reperfusion, rings
      of aorta were prepared and suspended in bioassay baths, contracted with
      phenylephrine, and examined for endothelium-dependent relaxation in response to
      acetylcholine and endothelium-independent relaxation using nitroglycerin.
      Endothelium-dependent relaxation to acetylcholine was impaired in rings from
      animals exposed to endotoxin-enhanced reperfusion injury at both 4 h and 24 h. At
      24 h of reperfusion the EC50 for acetylcholine relaxation was significantly
      increased from 45 +/- 8 nM to 258 +/- 105 nM. Endothelium-independent relaxation
      to nitroglycerin was not affected. The 21-aminosteroid Tirilazad mesylate (U
      74006F) prevented endothelial dysfunction; at 24 h of reperfusion the EC50 for
      acetylcholine relaxation in U-74006F-treated animals was 55 +/- 8 nM. Thus,
      endothelial function is impaired in this model of multiple organ failure and this
      impairment is prevented by Tirilazad mesylate.

PMID- 8856845
TI  - ABT-299, a novel PAF antagonist, attenuates multiple effects of endotoxemia in
      conscious rats.
AB  - ABT-299, a highly potent and selective platelet activating factor (PAF)
      antagonist, was found to be effective in rat models of endotoxic shock. ABT-299
      inhibited and reversed LPS-induced hypotension (ED50 of .008 mg/kg,
      intraarterially). When given prior to LPS challenge, ABT-299 (.1 mg/kg,
      intravenously) completely inhibited LPS-induced intestinal damage for as long as
      8 h after the administration of the antagonist. Pretreatment of rats with ABT-299
      (5 mg/kg, intravenously over 4 h) prevented by 85-95% symptoms of disseminated
      intravascular coagulation (DIC) induced by LPS, including thrombocytopenia,
      prolongation of prothrombin and partial thromboplastin time, decreased serum
      fibrinogen, and elevation of serum fibrinogen/fibrin degradation products. A .1
      mg/kg dose of ABT-299 administered orally or intravenously improved long-term
      survival to 80% and 90%, respectively, following a lethal dose (LD65) of LPS. ABT
      299 (.1 mg/kg) was also effective in preventing hypotension and gastrointestinal
      damage induced by lipoteichoic acid (LTA), a putative causative agent of shock in
      Gram-positive infections. These results illustrate the impressive potency and
      duration of action of ABT-299 and support the putative role of PAF in acute
      models of endotoxic shock.

PMID- 8856846
TI  - Differential effects of transforming growth factor-beta 1 on lipopolysaccharide
      induction of endothelial adhesion molecules.
AB  - In this report, we studied the effects of transforming growth factor (TGF)-beta 1
      on lipopolysaccharide (LPS)-induced expression of endothelial cell (EC) adhesion
      molecules. Confluent human umbilical cord vein EC cultures were stimulated with
      Escherichia coli LPS and TGF-beta 1, alone or in combination for various times
      and evaluated for expression of ICAM-1, E-selectin, and VCAM-1 by
      immunofluorescence and radioimmunoassay. Effects of LPS and/or TGF-beta 1 on cell
      growth were also studied by 3H-thymidine incorporation. Both LPS and TGF-beta 1
      alone stimulated EC expression of the adhesion molecules in a dose-dependent
      manner. The effects of TGF-beta 1 on LPS induction of the adhesion molecules
      varied with LPS concentration and treatment time, mode, and duration.
      Pretreatment with TGF-beta 1 for 24 h greatly augmented LPS induction of ICAM-1
      and VCAM-1 expression, but decreased E-selectin expression. TGF-beta 1 also
      enhanced expression of the adhesion molecules in cells that were pretreated with
      1 microgram/mL LPS for 60 min. Concomitant treatment with TGF-beta 1/LPS resulted
      in significant increases in ICAM-1 but decreases in VCAM-1 expression. TGF-beta 1
      effects on LPS induction of the adhesion molecules were more prominent at lower
      LPS levels (.001, .01 microgram/mL). Both LPS and TGF-beta 1 suppressed thymidine
      incorporation in a dose-related pattern. These data suggest that TGF-beta 1 has
      additive and antagonistic effects on LPS induction of the adhesion molecules and
      that the cell responsiveness to the stimuli in the expression is related to
      growth condition of the cells. In conclusion, our findings suggest that TGF-beta
      1 exhibits pro-inflammatory and anti-inflammatory activities in human endothelial
      cells and may play an important role in regulating leukocyte adherence and
      extravasation under LPS-induced inflammatory conditions.

PMID- 8856847
TI  - Alterations in endothelial barrier permeability in multiple organs during
      overactivation of macrophages in rats.
AB  - Macrophage hyperactivity has been suggested to play an important role in septic
      complications and the development of multiple organ failure. Intraperitoneal
      administration of macrophage stimulants, e.g., zymosan, induce a systemic
      inflammatory response, with concomitant gut origin sepsis, and organ dysfunction.
      However, little is known about alterations in endothelial permeability during
      macrophage hyperactivation. In the present study, the effect of macrophage
      hyperactivation on endothelial permeability, assessed by 125I-labeled HSA and
      51Cr-labeled EDTA, and the difference between cytolytic and noncytolytic
      inflammatory macrophages induced by i.p. injection of .25 or .50 mg/g of zymosan,
      concanavalin A (Con A) or thioglycollate medium (TM) diluted in 4 mL of paraffin,
      as well as the potential relationship with the doses used, were evaluated in the
      rat. Overactivation of cytolytic inflammatory macrophages induced a pronounced
      alteration in endothelial barrier permeability, characterized by a decrease in
      whole body plasma volume and an increase in whole body interstitial fluid volume,
      while overactivation of noncytolytic inflammatory macrophages only induced
      leakage of proteins and plasma to several of the organs studied. Macrophage
      activators, like zymosan, Con A and TM, exhibited varying effects on endothelial
      permeability related to the dose used. The results in the present study imply
      that overactivation of cytolytic inflammatory macrophages may play an important
      role in endothelial barrier injury and that zymosan possesses a more potent
      effect as compared to Con A when administered at the same dose.

PMID- 8856848
TI  - Heat shock pretreatment prevents hydrogen peroxide injury of pulmonary
      endothelial cells and macrophages in culture.
AB  - The purpose of the present study was to determine whether heat shock pretreatment
      would protect pulmonary endothelial cells and alveolar macrophages against
      hydrogen peroxide (H2O2)-induced injury. The bovine pulmonary artery endothelial
      cells (BPAECs) heat-shocked (42 degrees C for 2 h) prior to exposure to H2O2 (1
      mmol/L for 45 min) showed significant decrease in H2O2-mediated increment of
      release of lactate dehydrogenase and production of thiobarbituric acid-reactive
      substances, and obvious alleviation in H2O2-induced decrease in activities of
      catalase and superoxide dismutase. Heat-shocked (42 degrees C for 2 h) rat
      pulmonary alveolar macrophages (PAMs) also obtained acquired resistance to injury
      by subsequent exposure of 1, 2, or 3 mmol/L H2O2 for 45 min. Simultaneously with
      this acquired oxidative resistance, Northern blot analysis showed that heat
      shocked BPAECs and PAMs, contained an increased level of mRNA coding for the
      inducible form of heat shock protein 70 (HSP70), and Western blot analysis
      indicated that there were increased expression of HSP70. Inhibition of protein
      synthesis by cycloheximide (25 micrograms/mL) and inhibition of RNA synthesis by
      actinomycin D (5 micrograms/mL) prevented the cytoprotection against H2O2. These
      results are consistent with the hypothesis that heat shock pretreatment would
      protect pulmonary endothelial cells and alveolar macrophages against H2O2-induced
      injury, and possibly that HSPs play a role in this cytoprotection.

PMID- 8856849
TI  - Evaluation of enzyme-linked immunosorbent assays for quantitation of eicosanoid
      mediators of sepsis syndrome.
AB  - Thromboxane, prostacyclin, and the leukotrienes are eicosanoids that have been
      implicated as mediators of the host inflammatory response to infection and
      injury. Commercial enzyme-linked immunosorbent assays (ELISA) are being
      increasingly utilized to quantitate plasma eicosanoid concentrations in both
      clinical and experimental systemic inflammatory conditions. The objectives of
      this study were to 1) critically examine the performance characteristics of
      commercial ELISA kits for thromboxane B2, 6 keto-prostaglandin F1 alpha,
      leukotriene B4, and leukotrienes C4, D4, and E4; 2) apply the four ELISA kits in
      obtaining actual eicosanoid plasma values under both baseline and septic
      conditions; and 3) recommend quality control measures for general use. Although
      averages of multiple standard curves from individual assays were variable, there
      was a strong linear regression relationship between the backfit dose and nominal
      dose for each level of standard. Precision profiles constructed for each assay
      type defined a working range where the intra-assay coefficient of variation is
      less than 10%. Backfit doses deviated most from nominal doses at both extremes of
      the standard curves and this variation is reflected in the higher percentage
      errors in these regions. Recovery of each eicosanoid analyte was 96-103%.
      Calculated sensitivities were somewhat higher than the manufacturer's
      specifications. When applied to actual measurements in human and porcine plasma,
      the assays yielded values that fell within the working ranges of the standard
      curves with the exception of leukotriene B4. Thus, the ELISAs examined were
      reproducible, precise, and accurate within a specific working range for each
      assay type. However, internal controls were lacking in the commercial kits
      examined, which made assessment of intra- and inter-assay variation difficult.

PMID- 8856850
TI  - Steroid hormone alterations following induction of chronic intraperitoneal sepsis
      in male rats.
AB  - The influence of sepsis on male reproductive function in chronic animal models
      has not been extensively investigated. On the basis of earlier clinical studies,
      it was hypothesized that chronic intraperitoneal (i.p.) sepsis in rats would
      modulate the circulating levels of steroid reproductive hormones. Male Sprague
      Dawley rats (300-375 g) were randomized to septic and nonseptic groups. Sepsis
      was induced with cecal slurry (200 mg/kg/5 mL 5% dextrose in water (D5W); i.p.)
      in septic rats, while nonseptic rats received only sterile D5W. The rats (n = 8
      12) were catheterized to measure systemic hemodynamics and to collect blood at 0,
      12, 24, and 48 h after induction of sepsis/sham sepsis. A separate group of
      normal rats was included to serve as an unoperated control group. The plasma
      concentration of corticosterone, progesterone, and testosterone in serum was
      determined using radioimmunoassay. The heart rate was significantly increased at
      t = 12, 24, and 48 h following induction of sepsis. However, septic rats did not
      display any significant alterations in the mean arterial pressure and pulse
      pressure. Basal circulating concentrations of serum corticosterone, progesterone,
      and testosterone were 356 +/- 124 ng/mL, 2.37 +/- 1.03 ng/mL, and 1.88 +/- .29
      ng/mL, respectively, in the unoperated rats. At t = 0 h there was a significant
      increase in the levels of corticosterone in septic rats and in the levels of
      progesterone in both septic and nonseptic rats. The elevations in the
      concentrations of corticosterone and progesterone returned to basal values after
      24 and 48 h. The septic animals had significantly decreased levels of
      testosterone at t = 24 and 48 h as compared with basal values and nonseptic
      groups. Our model of sepsis produced a time-dependent decrease in levels of
      testosterone, an end product of male steroidogenesis. This, along with unchanged
      levels of corticosterone and progesterone at 24 and 48 h following sepsis,
      indicates that separate mechanisms for steroidogenesis regulating synthesis of
      these steroid hormones (progesterone and testosterone) occur with sepsis. It is
      concluded that in our chronic septic rat model, induction of i.p. sepsis produced
      dysfunction in steroidogenesis, which selectively affected the synthesis of
      testosterone.

PMID- 8856851
TI  - The International Spinal Research Trust's strategic approach to the development
      of treatments for the repair of spinal cord injury.
AB  - The International Spinal Research Trust (ISRT) has selected a sub-set of the key
      molecular and cellular events underlying spinal injury and nerve regeneration, to
      be focus of their funding and other means of research support. These priority
      targets are (i) to understand and to minimise the damage caused by spinal injury
      and the resulting inflammatory and fibrotic events, in order to prevent the
      establishment of a post-acute situation that is ill-placed for regeneration; and
      (ii) to understand and then to manipulate the integrated environment for regrowth
      that is created by the interplay of soluble and matrix- or membrane-associated
      factors, both trophic and inhibitory. Investigation and, ultimately, exploitation
      of these targets requires the development of standardised and representative
      animal models and the application of quantitative methods for assessing
      functional re-innervation. The ISRT will also sponsor the networking of different
      disciplines and technologies to apply the most productive skills to spinal
      repair.

PMID- 8856852
TI  - Folic acid and neural tube defects.

PMID- 8856853
TI  - Memorial lecture in honour of Dr Ailie Key.

PMID- 8856854
TI  - Cost of traumatic spinal cord injury in a population-based registry.
AB  - This prospective study examines a population based cohort of 115 Coloradans
      identified as having an acute traumatic spinal cord injury by the Spinal Cord
      Injury Early Notification System in 1989. Comprehensive medical cost and
      complication data were collected for the first 2 years of survival. Unlike
      previous cost studies, this group represents the broad spectrum of spinal cord
      injured persons, reflected in a truly population based sample. Nearly 22 million
      dollars were spent during the first 2 years post injury on behalf of these
      Coloradans. Care provided to the 27 persons with Frankel A, B or C tetraplegia
      accounted for $10.9 million (50%); $7.6 million (35%) was spent providing care
      for the 36 people with Frankel A, B or C paraplegia; and the remaining $3.3
      million (15%) was required for services provided to the 52 persons who had
      resolved to either Frankel D or E at acute care discharge. Of the $6.3 million
      that was spent post hospital discharge, $2.5 million (39%) is directly
      attributable to in-home care, and another $2.0 million (32%) is directly
      attributable to secondary medical complications. The most expensive complications
      occurred in the neurological, skin, respiratory and orthopedic body systems.

PMID- 8856855
TI  - Micturition disturbance in acute transverse myelitis.
AB  - In ten patients with acute transverse myelitis (ATM), seven patients had urinary
      retention, and the other three patients had difficulty in voiding within 1 month
      from the onset of the disease. Five of the patients with retention became able to
      urinate. After the mean follow-up period of 40 months, nine still had urinary
      symptoms including difficulty in voiding in five and urinary frequency, urgency
      and incontinence in four patients. Four patients had urinary disturbance as the
      sole sequel of ATM. Urodynamic studies performed on nine patients revealed that
      all of the three patients with the urgent incontinence had detrusor
      hyperreflexia, all of the four patients with retention had an areflexic
      cystometrogram as well as sphincter hyperreflexia, and three of five patients
      with voiding difficulty had detrusor-sphincter dyssynergia. An areflexic
      cystometrogram tended to change to a low compliance bladder, followed by detrusor
      hyperreflexia or a normal cystometrogram. Analysis of the motor unit potentials
      of the external sphincter revealed that two of the three patients had high
      amplitude or polyphasic neurogenic changes. Supranuclear as well as nuclear types
      of parasympathetic and somatic nerve dysfunctions seemed to be responsible for
      micturition disturbance in our patients with ATM.

PMID- 8856856
TI  - The prognosis and the treatment of patients with a C3/4 spinal cord injury.
AB  - Twenty patients with a C3/4 spinal cord injury have been treated in our hospital
      since 1974. There were 15 new patients. The average follow up period was 68
      months, ranging from 7 to 162 months. The 15 new cases were classified as Frankel
      A in nine cases, B in one, and C in five. Frankel A or B were usually accompanied
      by either an unstable spinal fracture or by spinal canal stenosis at the C3/4
      level. Twelve patients received surgery. At the most recent follow up, eight of
      the 15 patients (53.3%) had improved according to Frankel's classification. Five,
      all Frankel A on remission, have died between 2 and 156 months after injury.
      Seven patients required tracheotomy on account of severe respiratory disturbance.

PMID- 8856857
TI  - Radiculomedullary complications of cervical spinal manipulation.
AB  - Spinal manipulation is commonly used by some therapists for the treatment of
      cervical pain. Flexion-extension of the cervical spine produces sliding movements
      of one vertebra over the one below it, which leads to physiological reduction in
      the antero-posterior diameter of the spinal canal. Spinal manipulation provokes
      movements that exceed the physiological limits of these articulations and thereby
      lead to a more significant reduction of the canal diameter. In patients with pre
      existing stenosis of the canal or those with vertebral instability, these
      movements may cause (or aggravate) myelopathy. For this reason, a thorough
      neurological examination and cervical spine films should be considered mandatory
      in patients being considered for spinal manipulation. This report describes four
      patients with cervical myelopathy and/or radiculopathy caused or aggravated by
      spinal manipulation. In one patient, magnetic resonance scans before and after
      chiropractic treatment strongly suggests that the disc prolapse syndrome
      experienced by the patient was provoked by the spinal manipulation.

PMID- 8856858
TI  - Urethral opening pressure in patients with myelodysplasia.
AB  - We evaluated 60 patients with myelodysplasia using the urethral opening pressure
      (UOP) which is defined as the total intravesical pressure at the moment when
      urine passes through the external sphincter by the Crede or the Valsalva
      maneuver. Twenty nine of the patients showed UOP value greater than 35 cmH2O and
      31 below 35 cmH2O. In the high pressure group, patients showed a tendency to
      preserve sphincter activity and had mild paralysis of the lower extremities. In
      contrast, most of patients in the low pressure group showed an underactive
      sphincter and severe paralysis of the lower extremities. The incidence of
      deterioration of the upper urinary tract, vesicoureteral reflux (VUR) and bladder
      deformity were significantly high in the high pressure group than those in the
      low pressure group (75.9% vs 16.1%, 72.4% vs 22.6%, 82.8% vs 29.0%, respectively,
      P < 0.05). During the follow-up period (42 months on average), the voiding
      methods were changed in 15 patients from the Crede maneuver to clean intermittent
      catheterization, and total of 12 operations were performed (10 antiVUR operation
      and two with an ileocystoplasty). Finally, approximately 90% of the patients in
      both the high and the low pressure groups were evaluated as improved or stable in
      the upper urinary tract, VUR and bladder deformity after conservative or surgical
      managements. UOP is considered to be one of the useful parameters to select the
      high risk patient in the urological management of myelodysplastic patients.

PMID- 8856859
TI  - Traumatic spinal cord injuries in Istanbul.

PMID- 8856860
TI  - Plaque and gingivitis in spinal paralysed individuals.

PMID- 8856861
TI  - Importance of bladder biopsies in spinal paralysed individuals (SPI)

PMID- 8856862
TI  - Association between muscle trauma and heterotopic ossification in spinal cord
      injured patients.

PMID- 8856863
TI  - Noninvasive techniques for studying pathogenic bacteria in the whole animal.

PMID- 8856864
TI  - Toward anti-adhesion therapy for microbial diseases.

PMID- 8856865
TI  - Recent developments in theories of pathogenesis of AIDS.

PMID- 8856866
TI  - Immunological determinants of disease caused by respiratory syncytial virus.

PMID- 8856867
TI  - The life and times of an intestinal M cell.
AB  - Intestinal M cells are specialized epithelial antigen-sampling cells,
      strategically located over mucosal lymphoid follicles. They regulate the entry of
      antigen required for mucosal immune responses. There are several potential
      mechanisms involved in the induction of intestinal M cells. Both luminal antigen
      and B cells appear to have an influence on these altered epithelial
      differentiation pathways.

PMID- 8856868
TI  - DNA immunization.
AB  - Inoculation with plasmid DNA vectors encoding immunogenic proteins induces both
      humoral and cell-mediated immune responses, which often provide protective
      immunity. Although many questions regarding the mechanism, efficacy and safety of
      DNA immunization remain to be addressed, this approach may offer a safer and more
      cost-effective alternative to conventional vaccines.

PMID- 8856870
TI  - Environmental regulation of rhizobial symbiotic nitrogen fixation genes.
AB  - Adaptation of rhizobia to a symbiotic life style and synthesis of the nitrogen
      fixing apparatus are coordinated with nodule development by the microaerobic
      conditions prevailing in the central nodule tissue. Sensing and transduction of
      the "low oxygen' signal involves similar regulatory elements in different
      rhizobia, yet, these are combined in species-specific circuits.

PMID- 8856869
TI  - Viral inhibition of apoptosis.
AB  - Viral propagation is limited both by the host immune response and by apoptosis of
      infected cells. Viruses circumvent apoptosis by different mechanisms: direct
      inhibition of particular proteases involved in cell death, stimulation of anti
      death pathways or regulation of the activity of transcription factors monitoring
      cell survival.

PMID- 8856871
TI  - Receptors for gamma-interferon encoded by poxviruses: implications for the
      unknown origin of vaccinia virus.
AB  - Poxviruses encode soluble interferon-gamma receptors (IFN-gamma Rs) that inhibit
      IFN-gamma activity and play a major role in virus pathogenesis. In contrast to
      the highly species specific cellular homologues, the vaccinia IFN-gamma R has
      novel broad species specificity. This has implications for the unknown origin and
      natural host(s) of vaccinia virus, the vaccine used for smallpox eradication.

PMID- 8856872
TI  - Signal transduction in the cell cycle regulation of Caulobacter differentiation.
AB  - Caulobacter crescentus differentiates to form a new cell type during asymmetric
      cell division. Recent results indicate that signal transduction pathways mediated
      by protein kinases and essential response regulators play a central role in the
      regulation of development and cell division in response to cell cycle
      checkpoints.

PMID- 8856873
TI  - Instrument sterilization, skin preparation, and wound management.
AB  - Recent advances in instrument sterilization include the introduction of gas
      plasma sterilization and the increased use of glutaraldehyde. Gas plasma
      sterilization has the advantages of no toxic residue effects, reduced turnover
      time, and applicability for sterilization of heat- and moisture-sensitive
      instruments. Chlorhexidine gluconate (4%) appears to be a superior preoperative
      surgical scrub for both the surgeon and the patient because of its increased
      antimicrobial efficacy, residual activity, and minimal tissue reactions. There
      are many new wound dressings and topical medications for treatment of wounds, but
      the efficacy of most of these preparations has been evaluated only in humans,
      dogs, and cats. The ideal topical wound preparation and dressing for equine
      wounds, particularly wounds affecting the distal limb, have not yet been found.

PMID- 8856874
TI  - Surgical materials and wound closure techniques.
AB  - Recent innovations in surgical materials have helped to enhance wound healing and
      protect surgical wounds from infection. Materials such as polyglyconate have been
      evaluated in equine tissues and found efficacious. Other materials, such as
      poliglecaprone 25, appear to have qualities useful to equine surgery but are
      untested in equine tissues. Care must be taken to fully evaluate a new surgical
      material because its usefulness in equine tissues may not match that in human or
      laboratory animal tissues. Furthermore, use of disposable materials in surgery,
      although considered ideal for maintenance of sterility, may come under more
      scrutiny in the future as environmental issues gain prominence. We tend to
      reserve disposable materials for prolonged procedures and for procedures that
      carry high risk of failure if infection develops.

PMID- 8856876
TI  - Instrumentation and techniques for laparoscopic and thoracoscopic surgery in the
      horse.
AB  - Equine surgery continues to benefit from advances in laparoscopic techniques.
      Descriptions of the normal anatomy of the standing horse and advances in
      instrumentation have improved our ability to perform laparoscopic surgery in both
      standing and dorsally recumbent horses. The common uses for laparoscopy are
      diagnostic laparoscopy, cryptorchidectomy, ovariectomy, and diagnostic
      thoracoscopy. Other reported uses include inguinal hernia repair, ruptured
      bladder repair, and ventral colopexy.

PMID- 8856875
TI  - Instrumentation and techniques in equine gastrointestinal surgery.
AB  - Recent advances in abdominal surgical techniques in the horse have resulted in
      improved survival rates and reduced postoperative morbidity. The development of
      abdominal surgical procedures in horses has paralleled the development of safe
      anesthetic protocols and innovative technological advancements in humans.
      Irrespective of the species, the application of sound surgical principles is
      still the foundation of surgical intervention. This article describes recent
      advances in equine gastrointestinal surgical techniques. The availability and
      application of innovative intestinal surgical devices and their specific uses in
      equine gastrointestinal surgery are also described.

PMID- 8856877
TI  - Advances in equine arthroscopy.
AB  - Surgical procedures completed under arthroscopic guidance have become commonplace
      in many equine practices and have largely replaced surgery using arthrotomy
      incisions. With a limited amount of equipment, numerous diagnostic and surgical
      procedures can be completed. Surgeons need to become familiar with regional and
      intraarticular (intrasynovial) anatomy to ensure that proper surgical approaches
      are used, access to the lesion will be realized, and potential complications will
      be minimized. Specialized motorized instruments and surgical lasers are now
      available and may be useful in the treatment of selected clinical cases.

PMID- 8856878
TI  - Instrumentation and techniques in equine fracture fixation.
AB  - In recent years fracture fixation in the horse has changed significantly. New
      devices, mainly adapted from the human field, have been successfully introduced
      into large animal surgery. Examples of such implants include the DCS/DHS implant
      system, the self-tapping screw, the cannulated screw, and the pinless external
      fixator. However, new devices have also been developed exclusively for equine
      fracture management, including the interlocking intramedullary nail and the
      external skeletal fixation device. With these devices the surgeon has more
      options for repairing fractures in horses. Nevertheless, many problems are still
      unsolved. Indications exist that during the next few years new, exciting fracture
      fixation systems will be developed, providing further advancements in the quest
      for the ideal implant for horses. However, the development stages of these
      devices are such that mentioning the possibilities here is premature.

PMID- 8856879
TI  - Instrumentation and techniques for treating orthopedic infections in horses.
AB  - Orthopedic infections-those involving bones, joints, tendon sheaths, or bursae
      are some of the most difficult problems for equine surgeons to treat
      successfully. Sources of the infection are usually hematogenous, traumatic, or
      iatrogenic and knowledge of the most likely causative bacteria is very useful in
      selecting the most appropriate antimicrobial(s) to either prevent or treat these
      infections in horses. This article discusses the clinical findings, diagnosis,
      treatment, and prevention of orthopedic infections in horses. More recent
      treatment methods such as synovial drainage techniques (arthroscopy and
      arthrotomy), intrasynovial antimicrobials, regional perfusion of antimicrobials,
      and antimicrobial-impregnated polymethylmethacrylate (PMMA) beads or cylinders
      are also addressed.

PMID- 8856880
TI  - Instrumentation and techniques in locomotion and lameness.
AB  - The success of a clinical gait laboratory depends on choosing the right
      equipment, installing it correctly, running calibration checks, and having
      skilled technical and professional personnel. For kinematic analysis,
      videographic or optoelectronic systems are the method of choice, with 2-D data
      being adequate for the majority of equine evaluations. A force plate provides a
      precise description of the 3-D ground reaction force; transmission of the force
      through the body tissues is measured using strain gauges attached to the bones
      and tendons. Accelerometers bonded to the hoof wall provide information
      describing the properties of the work surface. To date, clinical applications of
      these techniques has been limited by the time and expertise required to extract
      appropriate data. In the future, as more of the data manipulation is automated,
      gait analysis will become more practical in a clinical setting; already,
      artificial neural networks are being trained to diagnose lameness using kinematic
      data input.

PMID- 8856881
TI  - Instrumentation and techniques in respiratory surgery.
AB  - In this article, videoendoscopy in conjunction with high-speed treadmill exercise
      and other specialized diagnostic techniques used to measure upper airway function
      are reviewed as they pertain to the four most commonly diagnosed functional upper
      airway obstructions: (1) laryngeal hemiplegia, (2) arytenoid chondritis, (3)
      epiglottic entrapment, and (4) intermittent dorsal displacement of the soft
      palate. Using experimental and clinical findings obtained with these new
      instruments and diagnostic techniques, current recommendations for surgery of
      these obstructions are presented.

PMID- 8856882
TI  - Instrumentation and techniques in transendoscopic upper respiratory tract laser
      surgery.
AB  - Transendoscopic laser surgery provides equine surgeons with a safe, reliable, and
      minimally invasive method of performing many surgical procedures in the upper
      respiratory tract. Although the Nd:YAG laser has proven efficacy, other newer
      lasers such as the diode and holmium: YAG lasers may prove to be useful tools for
      equine upper respiratory tract surgery. Long grasping forceps and a high quality
      fiberoptic or video endoscope are critical components necessary for performing
      transendoscopic laser surgery. For many of the most common upper respiratory
      tract abnormalities, a laryngotomy can be eliminated, morbidity is minimal, the
      horse can often return to normal exercise in approximately 7 to 14 days, and
      trainer and owner acceptance is excellent. Transendoscopic laser surgery is most
      likely to be cost effective in large referral practices or in a university
      setting.

PMID- 8856884
TI  - Government proposes precautionary controls on ovine offals.

PMID- 8856883
TI  - Instrumentation and techniques for carbon dioxide lasers in equine general
      surgery.
AB  - The carbon dioxide laser has become an important surgical instrument in human and
      veterinary medicine. The unique properties of this laser make it the instrument
      of choice for precise incision, coagulation, and vaporization of tissue at the
      body surface with minimal morbidity to the patient. This article describes the
      instrumentation and techniques used to perform a variety of equine general
      surgical procedures with the carbon dioxide laser. The benefits of surgery using
      the carbon dioxide laser include precise dissection with minimal trauma to
      adjacent tissues, good hemostasis, and the ability of the laser beam's thermal
      properties to kill bacteria or tumor cells in the operative field.

PMID- 8856885
TI  - Conservation of British wildlife.

PMID- 8856886
TI  - Progress in treating equine shock.

PMID- 8856887
TI  - Use of the relationship between blood lactate and running speed to determine the
      exercise intensity of horses.
AB  - Eight thoroughbred horses, trained for racing competition, were subjected to a
      standardised incremental speed test to determine the relationship between their
      blood lactate concentrations and running speed. Between 14 days before and 14
      days after completing the standardised exercise test, the horses were timed for
      runs of 2000 to 6000 m. The blood lactate concentration after each run was
      measured and compared with the blood lactate concentration predicted from the
      individual horse's blood lactate-running speed relationship curve determined from
      the standardised exercise test. The relationship between the predicted and
      measured lactate concentrations was evaluated by linear regression. For 42
      exercise runs there was a significant positive correlation between the measured
      and the predicted lactate concentrations and a significant regression: measured
      lactate (mmol/litre) = 1.01 predicted lactate (mmol/litre) -0.36 (r2 = 0.79,
      standard error of estimate 0-63 mmol/litre, P < 0.001). It was concluded that the
      standardised exercise test was a useful technique for predicting the blood
      lactate concentrations of horses after field exercise.

PMID- 8856888
TI  - Reduced conception rates in dairy cattle associated with serological evidence of
      Leptospira interrogans serovar hardjo infection.
AB  - Fertility data from 673 cows in five dairy herds with a moderate to high
      seroprevalence of microscopic agglutination titres (MAT) of > or = 1:10 against
      Leptospira interrogans serovar hardjo were collated to assess the relationship
      between pregnancy rates and antibody titres to serovar hardjo. A significant
      proportion of failures of conception (10 to 13 per cent, P < 0.001) were
      associated with MATs of 1:10 to 1:100; the overall pregnancy rate of the
      seronegative cows was 28.5 per cent higher (P < 0.001) than that of the cows with
      MATs of > or = 1:100. First service pregnancy rates showed a similar trend but
      the differences were significant (P < 0.05) only in cows with antibody titres >
      or = 1:30. An assessment of other possible risk factors for reduced pregnancy
      rates, such as lactation number and calving to first service interval, had no
      effect on the statistical results of the study or its conclusions.

PMID- 8856889
TI  - Viral aetiology of enzootic pneumonia in Danish dairy herds: diagnostic tools and
      epidemiology.
AB  - Ten outbreaks of calf respiratory disease in Danish dairy herds were investigated
      by lung lavage, and in eight of the herds paired blood samples were tested
      serologically. In six of the 10 herds bovine respiratory syncytial virus (BRSV)
      antigen was detected in the lung lavage fluids. In only one calf was coronavirus
      and BRSV detected simultaneously. The paired blood samples confirmed that four of
      the herds were BRSV-infected, and in one herd the BRSV infection was diagnosed by
      the paired blood samples alone. Significant increases in antibody titres against
      coronavirus were observed in two herds, both in combination with other
      virological agents. No adenovirus antigen was detected in any of the lavage
      samples, but in two herds a significant increase in antibody titres against
      adenovirus was observed. Parainfluenza-3 (PI-3) virus was not detected in the
      lung lavage fluids, and in four of the herds, no antibodies to PI-3 were
      detected. In three herds no viral involvement could be found. The findings
      suggest that BRSV may be an important causative agent in calf respiratory disease
      in Denmark, even in very young calves.

PMID- 8856890
TI  - Watery mouth disease in lambs: biochemical parameters before and after treatment.

PMID- 8856891
TI  - Peste des petits ruminants in goats in Pakistan.

PMID- 8856892
TI  - Effect of GnRH and hCG on ovulation and pregnancy in mares.

PMID- 8856893
TI  - Mandibular fibroblastic osteosarcoma in a three-month-old dog.

PMID- 8856894
TI  - Resistance to levamisole.

PMID- 8856895
TI  - Report of the first workshop on the genetic map of bovine chromosome 23.
AB  - A report of the first workshop on the genetic map of bovine chromosome 23 (BTA23)
      is given. Five laboratories contributed data from 29 loci, including a total
      11586 informative genotypes. The combined pedigrees represented 1930 potentially
      informative meioses. Eighteen of the 29 loci were common to two or more data sets
      and were used to construct a framework linkage map of BTA23. Twelve of the 18
      could be ordered on the linkage map with a likelihood ratio of greater than
      1000:1. Thus, a low resolution consensus map was constructed with a high level of
      support for order. The sex-averaged, female and male maps span 54.5, 52.7 and
      55.8 cM, respectively. Sex-specific differences in recombination frequency were
      identified for eight pairs of framework loci. Average genetic distance between
      framework loci on the sex-averaged map is 5.0 cM.

PMID- 8856896
TI  - Porcine alpha-1-antitrypsin (PI): cDNA sequence, polymorphism and assignment to
      chromosome 7q2.4- > q2.6.
AB  - A cDNA clone encoding the complete coding sequence for porcine alpha-1
      antitrypsin (or alpha 1-protease inhibitor, PI) was isolated and its DNA sequence
      determined. The cDNA is assumed to encode alpha-1-antitrypsin on the basis of its
      sequence similarity to the corresponding cDNAs for human, baboon, rat, mouse,
      sheep and cow. The porcine cDNA clone was used in conjunction with BamHI, KpnI,
      MspI, SacI, TaqI and XbaI to develop restriction fragment length polymorphism
      based genetic markers for linkage mapping in pigs. The cDNA has also been used to
      map the porcine PI locus to chromosome 7q2.4- > q2.6 by radioactive in situ
      hybridization. Thus, the PI locus has been added to the developing physical and
      genetic maps of the porcine genome.

PMID- 8856897
TI  - Sequence comparison of mitochondrial tRNA genes and origin of light strand
      replication in Bos taurus and Nellore (Bos indicus) breeds.
AB  - Although the complete bovine mitochondrial DNA molecule has been previously
      sequenced and sequence comparisons of the mitochondrial displacement loop have
      been performed, detailed sequence information is limited on coding regions of
      mitochondrial DNA within and among breeds of Bos taurus and Bos indicus. This
      study analysed polymorphism of the mitochondrial DNA transfer RNA genes for
      tryptophan, alanine, asparagine, cysteine, tyrosine and the origin of light
      strand replication among Ayrshire, Canadian, Belgium Blue, Brown Swiss, Hereford,
      Jersey, Limousine, Piedmontaise, Red Angus, Simmental (Bos taurus) and a Nellore
      (Bos indicus). Nucleotide sequence analysis of a 420-bp fragment of mitochondrial
      DNA comprising the five transfer RNA genes showed 100% homology among single
      individuals of the Bos taurus breeds. The Nellore breed showed guanine to adenine
      substitutions in the DHU arm of asparagine tRNA and in the origin of light-strand
      replication. This equates to a 0.5% sequence difference between the Nellore and
      Bos taurus breeds and may reflect an independent evolutionary origin of the
      species.

PMID- 8856898
TI  - A swine SINE (PRE-1 sequence) distribution in swine-related animal species and
      its phylogenetic analysis in swine genome.
AB  - The distribution of PRE-1 sequence (a swine SINE) among the animal species
      related to Sus scrofa, i.e. Phacochoerus aethiopicus and Tayassu tajacu, was
      examined by dot-blot analysis using PRE-1 sequences as a probe. This revealed
      that Phacochoerus aethiopicus and Tayassu tajacu contained PRE-1 sequences,
      amounts of which in their genomes are almost the same as that in the swine
      genome, indicating that these species separated after PRE-1 sequences
      proliferated to diversify in the genome. In order to estimate the time when the
      PRE-1 started to diversify in the swine genome, PRE-1 sequences were extracted
      from GenBank DNA database by homology analysis using the PRE-1 consensus sequence
      as a probe. The 22 PRE-1 sequences obtained were aligned and their phylogenetic
      relation was calculated by the neighbour-joining method. The result of the
      calculation combined with the mutation rate of the pseudogenes (r = 4.6 x 10(-9))
      indicated that the PRE-1 sequence diversified at least 43.2 million years ago.
      Taken together, the period of time since the separation of the three species, Sus
      scrofa, Phacochoerus aethiopicus and Tayassu tajacu, is currently estimated to be
      less than 43.2 million years.

PMID- 8856899
TI  - Denaturing gradient gel electrophoresis detection of polymorphism in a PCR
      fragment of sheep epidermal growth factor gene.
AB  - The ovine map is not yet well-developed, which represents a problem when looking
      for markers of a region of interest in sheep. A means of circumventing this is to
      use comparative mapping. In this study primers were determined using consensus
      sequences for the epidermal growth factor gene of humans, rats and mice, and an
      ovine epidermal growth factor gene fragment was amplified by polymerase chain
      reaction (PCR). A new set of specific ovine primers was chosen to study the
      polymorphism of this DNA fragment by denaturing gradient gel electrophoresis.
      Eighty-four individuals belonging to seven sheep breeds were studied with this
      technique and four alleles were detected. The heterozygosity rate was 0.57.
      Family analysis showed mendelian inheritance of the alleles. Usually, genetic
      analysis of type-I loci used in the comparative mapping is based on the detection
      of restriction fragment length polymorphisms in sheep DNA using cDNA probes from
      other species. Our work shows that another method, based on PCR and denaturing
      gradient gel electrophoresis techniques, can be efficiently used.

PMID- 8856900
TI  - Unequivocal identification of the equine Dcfmqr phenogroup.
AB  - An alloimmune reagent has been produced that distinguishes the equine factor Df
      in the D phenogroup, cfmqr, from that occurring in cefmqr and dfklr. Using this
      reagent it has been possible to correctly genotype Dc, d, f, k, l, m, q and r
      positive cells without recourse to family data.

PMID- 8856901
TI  - Detection of a new kappa-casein variant in milk of Pinzgauer cattle.
AB  - A new kappa-casein variant (kappa-CN G) with a frequency of 0.003 was
      demonstrated in Pinzgauer cattle from Austria and Bavaria, Germany by isoelectric
      focusing in polyacrylamide gels and by alkaline polyacrylamide gel
      electrophoresis. Kappa-CN G was not present in milk samples of Limpurger, another
      endangered breed.

PMID- 8856902
TI  - Chromosomal assignment of porcine EAD, EAO, LPR and P3 genes by linkage analysis.
AB  - A two-point linkage analysis was performed between blood group (14), allotype
      (8), polymorphic protein (11), DNA type I (2), and microsatellite (2) loci in
      Wild Boar x Pietrain and Meishan x Pietrain three-generation families. The
      following new pairwise linkages were detected: LPR-EAN (Zmax = 60.68, theta =
      0.055), EAD-GH1 (Zmax = 17.43, theta = 0.246), EAO-P3 (Zmax = 15.81, theta =
      0.239), and P3-S0003 (Zmax = 5.43, theta = 0.312). This study and published
      mapping data enabled the localization of LPR (LPR allotype) to chromosome 9, EAD
      (erythrocyte antigen D) to chromosome 12, and EAO (erythrocyte antigen O) and P3
      (P3 allotype) to the q arm of chromosome 6 with gene order S0003-P3-EAO, EAO
      being the most distal.

PMID- 8856903
TI  - A new DNA marker, U15557, is linked to protease inhibitor and adenylate kinase-1
      in the laboratory opossum, Monodelphis domestica.
AB  - A 323-bp DNA fragment (U15557) was isolated, cloned, and sequenced after
      polymerase chain reaction (PCR) amplification from Monodelphis domestica genomic
      DNA. A HindIII restriction fragment length polymorphism was identified in this
      species using the U15557 PCR, fragment as a hybridization probe. DNA samples
      exhibited either a 6.4 kb band, a 7.2 kb band, or both bands simultaneously.
      Behaviour of these two variants in family studies was consistent with codominant
      autosomal inheritance. Linkage between this marker and the loci encoding protease
      inhibitor (PI) and adenylate kinase 1 (AK1) was found in M. domestica.

PMID- 8856904
TI  - A parentage evaluation test in North American elk (Wapiti) using microsatellites
      of ovine and bovine origin.
AB  - DNA microsatellites originally detected in sheep and cattle are also detectable
      in North American elk (Wapiti) using polymerase chain reactions. We have
      developed a parentage test in elk using eleven microsatellite markers that are
      highly polymorphic and informative.

PMID- 8856905
TI  - Characterization and mapping of three bovine polymorphic microsatellite loci.

PMID- 8856906
TI  - Haplotypes of restriction polymorphisms as informative genetic markers at the
      ovine glutathione reductase (GSR) locus.

PMID- 8856907
TI  - Characterization of two polymorphic horse microsatellites: HMS15 and HMS20.

PMID- 8856908
TI  - A BalI RFLP at the goat beta-casein gene.

PMID- 8856909
TI  - A high-frequency TaqI polymorphism at the ovine phenylalanine hydroxylase
      (PAH)locus.

PMID- 8856910
TI  - A polymorphic microsatellite within the immunorelevant bovine lysozyme-encoding
      gene.

PMID- 8856911
TI  - Three polymorphic microsatellites for bovine chromosomes 7, 12 and 19.

PMID- 8856912
TI  - Equine dinucleotide repeat polymorphisms at loci LEX002, -003, -004, -005, -007, 
      008, -009, -010, -011, -013 and -014.

PMID- 8856913
TI  - A chinook salmon PCR-RFLP marker in the p53 locus.

PMID- 8856914
TI  - Identification of a G/C transversion polymorphism in intron 38 of the porcine
      skeletal muscle ryanodine receptor gene.

PMID- 8856915
TI  - Four equine dinucleotide repeats at microsatellite loci UCDEQ5, UCDEQ14, UCDEQ46
      and UCDEQ62.

PMID- 8856916
TI  - Detection of an MboI RFLP at the porcine clotting factor IX locus and
      verification of sex linkage.

PMID- 8856917
TI  - Trinucleotide repeat polymorphism at the alpha-enolase/tau-crystallin locus in
      ducks.

PMID- 8856918
TI  - Genetic variation in Australian Merino sheep.
AB  - Variation at 22 gene loci was investigated in a flock of Australian Merino sheep
      using restriction fragment length polymorphism (RFLP) analysis. Polymorphism was
      observed at 20 loci, including loci for wool keratin, hormone and immunoglobulin
      light chain genes. Eleven loci yielded unambiguous genotypes suitable for
      population data analysis. Average heterozygosity, determined from these and two
      monomorphic loci, was estimated as 0.107 (SE = 0.024). Average heterozygosity
      excluding all monomorphic data as estimated at 0.377 (SE = 0.031), which is
      comparable with human RFLP heterozygosities for loci chosen in the same way that
      we selected sheep loci.

PMID- 8856919
TI  - Development and mapping of polymorphic microsatellite markers derived from a
      chicken brain cDNA library.
AB  - Until now the genetic linkage map in chicken has ben based mainly on random
      genomic markers. The addition of expressed sequence tags (ESTs) to the genetic
      linkage maps is becoming more important because ESTs can form the basis for
      comparative mapping studies. This may be helpful for the detection of candidate
      genes for quantitative trait loci (QTLs). In our study we used a (TG)13 repeat as
      probe for the detection of microsatellites in a chicken brain cDNA library. After
      hybridization 0.15% of the cDNA clones gave a positive signal. The cDNA
      complexity of the library was high; of the 90 cDNA clones that were sequenced 60
      occurred only once. For 29 clones primer sets for the polymerase chain reaction
      could be developed. Twenty-one microsatellites were polymorphic on one or more of
      the test panels and 15 markers could be mapped on either or both of the
      international reference families. Because sequence homology between chicken and
      mammalian cDNAs is sometimes low it was difficult to assess the level of sequence
      homology that indicated a true homologous transcript. In our study seven cDNA
      cones, of which three could be mapped, showed a relatively high percentage of
      sequence homology with sequences found in other species. Because sequencing and
      mapping of expressed sequence tags in human and mouse is progressing very
      rapidly, it is predicted that further information will soon be readily available.
      Therefore, increasing the number of expressed sequences on the chicken genetic
      linkage map will be of value for comparative mapping studies in the near future.

PMID- 8856920
TI  - Mapping economic trait loci for somatic cell score in Holstein cattle using
      microsatellite markers and selective genotyping.
AB  - Marker-assisted selection (MAS) uses genetic marker genotypes to predict an
      animal's production potential and will provide additional selection information
      for progeny testing. With the discovery of highly polymorphic microsatellite
      markers, the tools now exist to begin the search for economic trait loci (ETL),
      which is the first step toward MAS. The objective of this study was to identify
      ETL for somatic cell score in an existing Holstein population. Using the
      granddaughter design, sons from seven grandsire families were genotyped with 20
      autosomal microsatellites from five chromosomes (4, 8, 13, 17, 23), with an
      emphasis on chromosome 23, which is the location of the bovine major
      histocompatibility complex (BoLA). Selective genotyping was used to reduce the
      number of genotypes required, in which the 10 highest and 10 lowest sons from the
      phenotypic distribution curve were tested (140 sons in seven families). One
      marker (513), located near BoLA, showed evidence of an ETL in three of five
      polymorphic families. Additional sons were genotyped from the five families to
      estimate the effect and to compare selective and 'complete' genotyping. Both
      methods detected an ETL at marker 513, but in different families. This study
      provides evidence of the usefulness of microsatellite markers and the
      granddaughter design in the detection of ETL; however, additional markers need to
      be evaluated to determine the usefulness of selective genotyping. Based on the
      results from the 20 studied markers, the most likely position of a somatic cell
      score ETL lies near marker 513, located on chromosome 23.

PMID- 8856921
TI  - Creation of a SINE enriched library for the isolation of polymorphic (AGC)n
      microsatellite markers in the bovine genome.
AB  - Trinucleotide (AGC)n microsatellites are found as 3' tails of the artiodactyl
      short insterspersed nuclear element (SINE) A-dimer. We describe a polymerase
      chain reaction (PCR)-based method for the construction of a plasmid library
      enriched for SINE (AGC)n microsatellites. By amplifying Sau3AI inserts with a
      conserved SINE primer and a flanking vector primer, a 35-fold enrichment of
      (AGC)n microsatellites over a conventional genomic library was obtained. The SINE
      primer was used for both sequencing of AGC-containing inserts and analysis of
      polymorphism. Twenty-three unique reverse primers were synthesized and used on
      bovine genomic DNA, 21 producing PCR products of expected size. Five polymorphic
      (AGC)n microsatellites with 2-4 alleles each were characterized. Allele sizes
      differed by a 3 bp motif and lacked the stutter bands associated with
      dinucleotide repeats. A tendency of increased polymorphism for longer AGC repeat
      arrays was observed. High stringency selection for positive clones containing
      eight or more AGC repeats can thus facilitate the isolation of polymorphic (AGC)n
      microsatellites. Enrichment for (AGC)n microsatellites by SINE-vector PCR can be
      applied to other bovidae species, such as sheep or goat, containing the
      artiodactyl SINE elements.

PMID- 8856922
TI  - Physical mapping confirms that sheep chromosome 10 has extensive conserved
      synteny with cattle chromosome 12 and human chromosome 13.
AB  - The following loci, on human chromosome 13, have been newly assigned to sheep
      chromosome 10 using chromosomally characterized sheep-hamster cell hybrids: gap
      junction protein, beta 2, 26 kDa (connexin 26) (GJB2); gap junction protein,
      alpha 3, 46 kDa (connexin 46) (GJA3), and esterase D/formylglutathione hydrolase
      (ESD). This assignment of ESD is consistent with comparative mapping evidence,
      but not with an earlier report of it on sheep chromosome 3p26-p24. Cell hybrid
      analysis confirmed the location of another chromosome 13 locus, retinoblastoma 1
      (including osteosarcoma) (RB1), and the anonymous ovine genomic sequence RP11 on
      sheep chromosome 10. Isotopic in situ hybridization was used to regionally
      localize RP11 on to sheep 10q15-q22. The location of microsatellites AGLA226,
      OarDB3, OarHH41, OarVH58, and TGLA441, previously assigned to sheep chromosome 10
      by linkage analysis, was confirmed by polymerase chain reaction using the cell
      hybrid panel. These mapping data provide further evidence that sheep chromosome
      10 is the equivalent of cattle chromosome 12, and that these chromosomes show
      extensive conserved synteny with human chromosome 13.

PMID- 8856923
TI  - A comprehensive linkage map of the pig based on a wild pig-Large White
      intercross.
AB  - A comprehensive linkage map, including 236 linked markers with a total sex
      average map length of about 2300 cM, covering nearly all parts of the pig genome
      has been established. Linkage groups were assigned to approximately all 18
      autosomes, the X chromosome and the X/Y pseudoautosomal region. Several new gene
      assignments were made including the assignment of linkage group U1 (EAK-HPX) to
      chromosome 9. The linkage map includes 77 types I loci informative for
      comparative mapping and 72 in situ mapped markers physically anchoring the
      linkage groups on chromosomes. A highly significant heterogeneity in
      recombination rates between sexes was observed with a general tendency towards an
      excess of female recombination. The average ratio of female to male recombination
      was estimated at 1.4:1 but this parameter varied between chromosomes as well as
      between regions within chromosomes. An intriguing finding was that blood group
      loci were overrepresented at the distal ends of linkage groups.

PMID- 8856924
TI  - Detection of a common BoLA-DRB3 deletion by sequence-specific oligonucleotide
      typing.
AB  - The bovine MHC clas II allele BoLA-DRB3*2A has an amino acid deletion of unknown
      function at codon 65 in the second exon, which codes for the antigen-binding
      site. Sequence-specific oligonucleotides were designed based on published
      nucleotide sequences on BoLA-DRRB3 alleles, and used to detect this deletion in
      51 Hereford cattle. Probes 65+ and 65- detect the presence or absence of codon 65
      respectively. Oligonucleotide probes were labelled with Digoxigenin (DIG),
      hybridized to dot blots of BoLA-DRB3 exon 2 polymerase chain reaction (PCR)
      product, and detected by chemiluminescence. Of the 51 animals screened, two were
      homozygous and 11 were heterozygous for the deletion at codon 65. The methodology
      described here provides the necessary tools to screen rapidly for this deletion
      in a large number of animals in order to study its effect on antigen binding and
      immune response.

PMID- 8856925
TI  - Partial characterization of porcine obesity gene (OBS) and its localization to
      chromosome 18 by somatic cell hybrids.
AB  - Degenerate primers based on human and mouse obesity gene (OBS) sequencing data
      were used in the reverse transcriptase-polymerase chain reaction (RT-PCR) of
      total RNA from pig white adipose tissue. Both strands of the resultant pig-
      specific 325 bp DNA fragment were sequenced. Comparison of the obtained sequence
      with known sequences revealed an 86% identity with the human and 84% identity
      with the mouse OBS cDNA. The OBS gene was physically mapped to pig chromosome 18
      by PCR analysis of somatic cell hybrids, using pig-specific primers. This result
      is consistent with the recent assignment of the human OBS gene to chromosome 7
      and the observation made by comparative mapping that by using a human chromosome
      7 specific library two segments of conserved synteny were detected on porcine
      chromosomes 9 and 18. We conclude the border of conserved synteny to be in the
      7q31-7q32 region of the human chromosome.

PMID- 8856926
TI  - Evidence for a single pedigree source of the hyperkalemic periodic paralysis
      susceptibility gene in quarter horses.
AB  - The pedigree origin of a base pair substitution in the horse muscle sodium
      channel gene that confers susceptibility to the muscle disease hyperkalemic
      periodic paralysis (HYPP) was investigated with a set of 978 Quarter Horses. The
      horses were chosen at random, based on a collection of blood samples taken
      between 1989 and 1991 to meet parentage testing requirements, primarily but not
      exclusively from breeding stallions. The frequency of Quarter Horses positive for
      the base pair substitution, all heterozygotes, was 4.4%, which corresponds to an
      allelic frequency of 0.02. All horses positive for the gene traced to a single
      previously identified stallion as first, second or third generation descendants.
      A higher frequency of the HYPP susceptibility trait than expected by random
      occurrence was found among his descendants in this study.

PMID- 8856927
TI  - A MspI polymorphism in the bovine ornithine decarboxylase gene and its possible
      association with selection for milk production in Holstein bulls.
AB  - A polymerase chain reaction (PCR)-based method for detection of a MspI
      restriction fragment length polymorphism (RFLP) in the bovine ornithine
      decarboxylase gene was developed, and the allele frequencies of the polymorphism
      in two groups of Holstein bulls representing progeny-tested bulls during the
      1950s-1960s and 1980s, respectively, were estimated. The frequencies of the MspI(
      ) allele ere 0.229 and 0.077 and that of MspI(+) were 0.771 and 0.923 in the
      progeny-tested bulls of the 1950s-1960s and 1980s, respectively. The difference
      in allele frequencies between the two groups was statistically significant (P <
      0.005). Genetic drift could be responsible for the changes in allele frequencies;
      however, it could also be possible that selection for milk production was
      associated with the changes of the allele frequencies in the two bull
      populations.

PMID- 8856928
TI  - An anonymous horse probe detects a HaeIII RFLP.

PMID- 8856929
TI  - A PvuII RFLP at the ovine placental lactogen CSH1 locus.

PMID- 8856930
TI  - Four horse genomic fragments containing minisatellites detect highly polymorphic
      DNA fingerprints.

PMID- 8856931
TI  - A polymorphic bovine dinucleotide repeat DXYS4 (IOZARA 1489) at the pseudo
      autosomal region of the sex chromosomes.

PMID- 8856932
TI  - A polymorphic bovine dinucleotide repeat D17S29 (IOZARA 975) at chromosome 17q26.

PMID- 8856933
TI  - Ovine dinucleotide repeat polymorphism at seven anonymous loci.

PMID- 8856934
TI  - A BsmAI PCR/RFLP in the bovine microtubule-associated protein-5 (MAP1B)gene.

PMID- 8856935
TI  - Microsatellite mapping of the brain natriuretic peptide (BNP1) locus to porcine
      chromosome 6.

PMID- 8856936
TI  - Equine dinucleotide repeat loci from LEX025 to LEX033.

PMID- 8856937
TI  - VNTR at porcine GPI locus.

PMID- 8856938
TI  - Fifteen polymorphic dinucleotide microsatellites in llamas and alpacas.

PMID- 8856939
TI  - PCR/RFLP marker in the canine opsin gene.

PMID- 8856940
TI  - Determination of cyanide using a microbial sensor.
AB  - A microbial cyanide sensor was prepared, consisting of immobilized Saccharomyces
      cerevisiae and an oxygen electrode. When the electrode was inserted into a
      solution containing glucose, the respiration activity of the microorganisms
      increased. The change in the respiration activity is monitored with the oxygen
      electrode. When cyanide is added to the sample solution, the electron transport
      chain reaction of the respiration system in the mitochondria is inhibited,
      resulting in a decrease in respiration. The inhibition is caused by cyanide
      binding with respiration enzymes such as the cytochrome oxidase complex in the
      mitochondrial inner membrane. Therefore, the cyanide concentration can be
      measured from the change in the respiration rate. When the sensor was applied to
      a batch system at pH 8.0 and 30 degrees C, the cyanide calibration curve showed
      linearity in the concentration range between 0.3 microM and 150 microM CN-.

PMID- 8856941
TI  - Antigen-antibody binding kinetics for biosensors. Changes in the fractal
      dimension (surface roughness) and in the binding rate coefficient.
AB  - The diffusion-limited binding kinetics of antigen in solution to antibody
      immobilized on a biosensor surface is analyzed within a fractal framework.
      Changes in the fractal dimension, Df observed are in the same and in the reverse
      directions as the forward binding rate coefficient k. For example, an increase in
      the concentration of the isoenzyme human creatine kinase isoenzyme MB form (CK
      MB) (antigen) solution from 0.1 to 50 ng/mL and bound to anti-CK-MB antibody
      immobilized on fused silica fiber rods leads to increases in the fractal
      dimension Df from 0.294 to 0.5080, and in the forward binding rate coefficient k
      from 0.1194 to 9.716, respectively. The error in the fractal dimension Df
      decreases with an increase in the CK-MB isoenzyme concentration in solution. An
      increase in the concentration of human chorionic gonadotrophin (hCG) in solution
      from 4000 to 6000 mIU/mL hCG and bound to anti-hCG antibody immobilized on a
      fluorescence capillary fill device leads to a decrease in the fractal dimension
      Df from 2.6806 to 2.6164, and to an increase in the forward binding rate
      coefficient k from 3.571 to 4.033, respectively. The different examples analyzed
      and presented together indicate one means by which the forward binding rate
      coefficient k may be controlled, that is by changing the fractal dimension or the
      "disorder' on the surface. The analysis should assist in helping to improve the
      stability, the sensitivity, and the response time of biosensors.

PMID- 8856942
TI  - Purification and properties of carnitine acetyltransferase from citric acid
      producing Aspergillus niger.
AB  - Carnitine acetyltransferase was purified from the citric acid producing A. niger
      mycelium with a protein band showing a relative molecular weight of 77,000 and a
      pH optimum of 7.3. The K(m) values for the purified enzyme for acetyl-CoA and for
      carnitine were 0.1 mM and 1 mM, respectively. Carnitine acetyltransferase was
      located both in the mitochondria and in the cytosol. Both mitochondrial and
      cytosolic enzyme were purified using ammonium sulfate precipitation, Mono Q and
      Superose 12 separation. Regarding the localization, except for maximum velocity,
      there were no differences observed in substrate specificity and inhibition.
      Inhibition of the enzyme with micromolar concentrations of Cu2+ could contribute
      to a greater citric acid biosynthesis. Carnitine acetyltransferase can be
      considered as an enzyme necessary for the transport of acetyl groups through
      mitochondrial membrane in both directions.

PMID- 8856943
TI  - Biomethanation of a mixture of salty cheese whey and poultry waste or cattle
      dung. A study of effect of temperature and retention time.
AB  - This paper describes the results of a study aimed at improving the efficiency of
      anaerobic digestion of salty cheese whey in combination with poultry waste or
      cattle dung. Best results were obtained when salty cheese whey was mixed with
      poultry waste in the ratio of 7:3, or cattle dung in the ration of 1:1, both on
      dry weight basis giving maximum gas production of 1.2 L/L of digester/d with
      enriched methane content of 64% and 1.3 L/L of digester/d having methane content
      of 63% respectively. Various conditions such as temperature and retention time
      have been optimized for maximum process performance.

PMID- 8856944
TI  - Effect of glucan immunomodulator on the immune response and larval burdens in
      mice with experimental toxocarosis.
AB  - Glucan immunomodulator, combined with immunoglobulin and zinc (GI), was tested in
      mice infected with Toxocara canis for its effects on the immune response and
      parasite recovery. Infection with 2 500 T. canis eggs per mouse induced a short
      term depression of the proliferative response of T cells to phytohemaglutinin
      from Day 35 to a Day 49 post infection (p.i.). GI given in two doses at the start
      of the experiment markedly stimulated and restored cell proliferation at Days 21
      63 p.i. Infection resulted in significant increase in specific circulating
      antibody level at Days 21 and 35 p.i. A striking reduction in the number of T.
      canis larvae, after GI administration was observed in the muscles of the GI
      treated mice, compared with the untreated animals.

PMID- 8856945
TI  - Eimeria alabamensis coccidiosis in grazing calves: control by a long-acting
      baquiloprim/sulphadimidine bolus.
AB  - The excretion of Eimeria oocysts, the faecal dry matter and the weight gain of
      three groups of 12 calves, were compared during their first 20 days of grazing on
      a pasture known to have been contaminated with oocysts of Eimeria alabamensis
      during the previous year. On the day of turnout (day 0) the calves in group 1
      were each treated with one bolus per 200 kg bodyweight containing 1.6 g
      baquiloprim and 14.4 g sulphadimidine. The calves of group 2 received the same
      treatment on day 3, and the calves of group 3 were left untreated. Eleven of the
      untreated calves developed clinical coccidiosis due to E. alabamensis and
      excreted more than 850,000 oocysts/g of faeces 8-10 days after turnout. Seven of
      the calves in group 1 and five of those in group 2 developed diarrhoea, but it
      was milder and/or less persistent than in the untreated calves. The treated
      calves excreted significantly fewer oocysts and lost significantly less weight
      than the untreated calves. On day 21 all the calves were housed and on day 27
      they were challenged with 10 million sporulated oocysts of E. alabamensis and
      turned out on to the same pasture. Only minor clinical signs were observed in
      some of the calves, indicating development of immunity in all groups. However,
      there was a tendency for the calves treated on day 3 to excrete more oocysts and
      to gain less weight than the other calves.

PMID- 8856946
TI  - Genetic variability in Italian sheep isolates of Echinococcus granulosus.
AB  - The possible polymorphism of distinct Italian Echinococcus granulosus isolates
      was evaluated by RAPD-PCR using five arbitrarily chosen random primers. Sheep DNA
      was used as control in each RAPD-PCR to ascertain the host DNA contamination.
      Distinct amplification patterns were detected for each isolate revealing
      identical bands, with the same or different intensity, as well as distinct bands.
      The results of this study confirm the usefulness of RAPD-PCR technique in genetic
      typing of parasites and show the existence of genetic variability within the
      Italian E. granulosus sheep strain.

PMID- 8856947
TI  - Immunisation of calves against Eimeria alabamensis coccidiosis.
AB  - Twelve calves which had been immunised with a trickle dose of altogether 100,000
      oocysts of Eimeria alabamensis 16 days before turnout and 12 uninoculated calves
      were monitored during their first 20 days of grazing on a pasture naturally
      contaminated with oocysts of E. alabamensis. Eleven of the uninoculated calves
      developed gruel-like diarrhoea 3-6 days after turnout and excreted more than
      850,000 oocysts/g of faeces (OPG) a few days later. In contrast, none of the
      immunised calves developed clinical coccidiosis and most of them excreted only a
      few oocysts. They lost on average 18 kg less in bodyweight than the unimmunised
      control calves. On day 21 all the calves were rehoused and on day 27 they were
      challenged with 10 million sporulated oocysts of E. alabamensis and turned out
      onto the same pasture. Only insignificant clinical signs were observed in 2 of
      the immunised calves and in one of the control calves. It was concluded that
      immunisation is a promising control measure for E. alabamensis coccidiosis.
      However, fewer or attenuated oocysts must be used, as 9 of the 12 inoculated
      calves developed clinical coccidiosis before turnout as a result of the
      immunisation doses.

PMID- 8856948
TI  - Studies on the effect of fenbendazole and mebendazole on some enzymes of swine
      kidney worm Stephanurus dentatus.
AB  - The effect of fenbendazole and mebendazole on the activity of some enzymes of the
      homogenates of swine kidney worm Stephanurus dentatus was investigated.
      Fenbendazole at 10(-5) M inhibited malate oxidation by 49% and 51% and
      oxaloacetate reduction by 33% and 40% whereas, mebendazole at 10(-5) M diminished
      malate oxidation by 25% and 35% and oxaloacetate reduction by 12% and 14% in male
      and female S. dentatus, respectively. Lactate dehydrogenase activity was
      inhibited by 45% and 50% in male and female worm respectively by 10(-5) M
      fenbendazole. Aldolase activity in both male and female S. dentatus was inhibited
      by 10(-5) M fenbendazole and mebendazole. Fenbendazole at 10(-5) M caused
      moderate inhibition of acid and alkaline phosphomonoesterases but mebendazole did
      not show a significant effect on these enzymes. Cholinesterase activity was not
      affected significantly with either compound. The possible mode of action of the
      two compounds is compared.

PMID- 8856949
TI  - Living systems theory as a paradigm for organizational behavior: understanding
      humans, organizations, and social processes.
AB  - Living systems theories have been used to model human, organization, and
      communication processes. This paper attempts to describe these models and to
      highlight the isomorphisms among the models. Particular emphasis is given to self
      regulating properties of humans as a subsystem of social systems. Attention is
      given to the advantages of generalizing across levels and phenomena and
      integrating the middle-range theories that dominate the field of organizational
      behavior. Three broad recommendations for future research are discussed.

PMID- 8856950
TI  - Langsian psychology and physics.
AB  - This paper relates the primitives of Robert J. Langs' psychology to those of
      physics. The off-boundary properties of all known natural processes are decided
      by their boundary behavior. Langs' formulations add the process of psychotherapy
      and general interpersonal exchange, that is two or more party dialogues, to this.
      His theory distinguishes the boundary, as does physics, into a frame and two
      sided action site, referred to as a gate here. His ideas develop by moving from
      data on the boundary as a gate to the nature of the frame. His line of approach
      contrasts with Freud's direction toward the process interior and to Jung's across
      it. Placing his boundary ideas into where he enters psychology repeats a line of
      thought in the history of physics on the relation of a system to its environment.
      This paper notes that much of Freud's theory is grounded in the first law of
      thermodynamics and Jung's the second. Langs' theory subsumes both laws with a
      holistic boundary model.

PMID- 8856951
TI  - Gender, status and 'powerless' speech: interactions of students and lecturers.
AB  - The present study investigated whether the use of 'powerless' speech was affected
      by role status, speaker's gender and gender of another participant. Fifty-two
      university lecturers and 156 students participated. Students were paired with a
      lecturer or student of the same or opposite sex. The findings placed a question
      mark over the link between powerless speech and individuals of low role status.
      Moreover, against hypothesis, speaker's gender and gender of partner did not
      affect the use of qualifiers or fillers, although they affected the use of tag
      questions and some types of hesitation. A qualitative analysis was also conducted
      which suggested that the powerless features were, in fact, multi-functional with
      respect to power. In addition, the importance of a variety of interactional
      techniques, such as credibility techniques, in the creation or negotiation of
      relational power was documented. As a whole, these findings highlight problems
      with the concept of 'powerless' speech, at least with respect to relational
      power.

PMID- 8856952
TI  - A methodological note on the application of the generalized grid technique in the
      measurement of perceived intercultural distance.
AB  - A renewed interest in the concept of perceived 'social distance' has recently
      occurred in relation to intercultural perception. The research reported here
      examines the utility of the generalized grid technique in measuring intercultural
      distance in a sample of English adolescents. The methodology described offers
      some advantages in ease of administration and comprehension by participants and a
      form of analysis that allows for the representation and examination of patterns
      of response of numerous individuals collectively.

PMID- 8856953
TI  - Disinfection by-products in the chlorination of organic nitrogen compounds: by
      products from kynurenine.
AB  - Volatile by-products in the chlorination of 3 humic acids as naturally-occurring
      substances and 37 nitrogen compounds normally found in excrement were analyzed,
      and as result kynurenine, a urinary metabolite of tryptophan was found a suitable
      model compound for dichloroacetonitrile-forming precursors. Possible pathways for
      the formation of chlorination by-products from kynurenine were also proposed by
      identification and kinetic properties of by-products decomposed further from each
      product.

PMID- 8856954
TI  - Estimated intake of PCDDs, PCDFs and co-planar PCBs in individuals from Madrid
      (Spain) eating an average diet.
AB  - The estimated intake of PCDD/Fs and co-planar PCBs associated with an average
      diet consumed in Spain was investigated. The estimated total average intake for
      PCDDs and PCDFs from an average spanish diet was found to be 142 pg I-TEQ/day
      (2.4 pg I-TEQ/Kg b.w./day, for a 60 Kg person). PCDDs provided almost 80% of the
      total dioxin equivalents. This represents the upper bound estimate. If
      concentrations less than the LOD are taken as equal to zero, then the estimated
      average intake would be 81 pg I-TEQ/day which is the lower bound estimate. Data
      reported are in good agreement with those reported for other countries.

PMID- 8856955
TI  - Occurrence of persistent organochlorine contaminants in human milk collected in
      several regions of Czech Republic.
AB  - The concentrations of persistent organochlorine contaminants including
      polychlorinated biphenyls (PCBs), DDT (its isomers and metabolites),
      hexachlorobenzene (HCB) and isomers of hexachlorocyclohexane (HCH) have been
      determined in human milk samples from the three regions in the Czech Republic.
      Results were generated by the congener-specific analyses (two-dimensional high
      resolution gas chromatography). The results are compared with the similar studies
      from other industrial countries (Norway, Great Britain, the Netherlands and
      Germany). Typical patterns of major PCBs contained in analyzed breast milk
      samples are presented. PCB No.153 was the dominant congener in all the samples. A
      good correlation was found between the sum of PCBs and PCB No.:153 (r = 0.99),
      constitutes approx. 30% of calculated PCBs content.

PMID- 8856956
TI  - Solid phase extraction of 2,4-D from human urine.
AB  - A method for determining urinary concentrations of 2,4-D in samples collected
      from non-occupationally, environmentally exposed individuals was developed. The
      2,4-D was extracted from fortified human urine samples using octadecylsilane
      solid phase extraction cartridges. The average percent recovery for urine samples
      spiked at 2 and 20 ng/mL was 100% and 93%, respectively. The method detection
      limit was estimated to be 0.75 ng of 2,4-D per mL of urine based on a 10 mL
      sample size. The potential use of 2,4-dichlorophenylacetic acid as a surrogate
      standard was also investigated.

PMID- 8856957
TI  - L-cystine-di-beta-naphthylamidase activity in plasma of the snake Bothrops
      jararaca after chronic challenges of water balance.
AB  - Plasma protein, osmolality and L-cystine-di-beta-naphthylamidase activity were
      measured in Bothrops jararaca snakes submitted to normal hydration, water
      deprivation, water loading, salt loading or argvasotocin injections. Protein and
      osmolality were similar for male and female snakes in all treatments. Protein
      content was similar in all treatments, indicating the ability of the animals to
      maintain fluid balance between the vascular and extravascular compartment under
      osmotic challenges. Osmolality was increased in water-deprived and salt-loaded
      and was decreased in water-loaded animals compared with normally hydrated or
      argvasotocin-injected snakes. Enzymatic activity differed between males and
      females and was higher in salt-loaded females and in arg-vasotocin-injected
      females and males than in water-loaded snakes. A positive linear regression
      between osmolality and L-cystine-di-beta-naphthylamidase was obtained for female
      snakes (correlation coefficient = 0.6162, P < 0.01). The data show a role of arg
      vasotocin in the consistent relationship between water balance and this sex
      related aminopeptidase activity.

PMID- 8856958
TI  - Comparison of endothelium-derived relaxing factor activity between nonpregnant
      and pregnant rats.
AB  - The tension of isolated ring preparation of aorta from nonpregnant and pregnant
      rats was measured isometrically to study the effect of pregnancy on endothelium
      derived relaxing factor activity. Contraction in response to norepinephrine and
      potassium chloride was greater in aortae from nonpregnant rats than in those from
      pregnant rats. The endothelium-dependent relaxation that was caused by
      acetylcholine (10(-10)-3 x 10(-9) M) in aortae precontracted with norepinephrine
      was significantly enhanced in aortae from pregnant rats compared with the
      relaxation in those from nonpregnant rats. NG-nitro-L-arginine methyl ester (L
      NAME) inhibited the endothelium-dependent relaxation in both aorta from pregnant
      and nonpregnant rats. L-Arginine reversed the inhibition of L-NAME. Those results
      suggest that the enhanced endothelium-derived relaxing factor activity in rats
      aortae is associated with pregnancy.

PMID- 8856959
TI  - Glucose-6-phosphate dehydrogenase activity in erythrocytes from chronically
      copper-poisoned sheep.
AB  - The present study was undertaken to investigate the capacity to generate reducing
      equivalents in erythrocytes from experimentally copper-poisoned sheep. Ten ewes
      were dosed orally with CuSO4 to induce the Cu toxicity. Copper dosing was stopped
      at the first day of hemolysis. The activity of glucose-6-phosphate dehydrogenase
      (G6PD) in the erythrocytes, the levels of reduced glutathione (GSH) and glucose
      (in serum and erythrocytes) was examined at frequent intervals. The copper
      poisoned sheep had reduced levels (25-35% less) of glucose in serum and
      erythrocytes than controls. The activity of G6PD in erythrocytes from sheep was
      50-60% of typical levels found in human erythrocytes. Immediately before the
      hemolytic period, the copper-poisoned sheep showed decreased activity of G6PD,
      declining to 65% of the initial activity. In addition, we found decreased blood
      levels of reduced GSH in copper-poisoned sheep. There appears to be a
      relationship between decreased capacity to generate reducing equivalents and the
      overload of copper in sheep erythrocytes.

PMID- 8856960
TI  - Effects of destruxins, cyclic depsipeptide mycotoxins, on calcium balance and
      phosphorylation of intracellular proteins in lepidopteran cell lines.
AB  - The influence of the destruxin E, cyclodepsipeptidic mycotoxin produced by the
      filamentous entomopathogenic fungus Metarhizium anisopliae, on calcium fluxes and
      protein phosphorylation of in vitro cultivated lepidopteran cell lines have been
      studied. The use of the fluorescent calcium indicator Fura 2 AM did not show a
      fast increase in the level of cytosolic calcium in lepidopteran and human cell
      lines treated with dtx E. In contrast, 45Ca+2 assays detected a late but
      significant calcium influx in insect cells exposed to dtx E and A for at least 30
      min. This effect was not inhibited by calcium channel blockers with the exception
      of nifedipine 25 microM. A viral treatment potentiated the effect of dtx E on
      calcium balance. Dtx E also induced a strong, fast (10 min), transient
      phosphorylation of high molecular weight (250 kDa) cellular proteins. The
      activation of phosphorylation was only partially inhibited by EDTA. This study
      provides the first direct evidence of dtx E influence on calcium fluxes and
      protein phosphorylation.

PMID- 8856961
TI  - Scleroglucan.
AB  - Cultures of filamentous fungi that secrete significant amounts of
      exopolysaccharides are among the most difficult of fermentation fluids,
      presenting difficulties in the areas of aeration, agitation, mixing, and control
      that may in turn impact the physiology of the microorganism in an undesirable
      manner. The fungus Sclerotium glucanicum, which produces a potentially useful
      exopolysaccharide known as scleroglucan, illustrates many such difficulties. This
      review discusses in detail the range of physiological studies on the producing
      microorganism itself, including those concerning formation of "undesirable"
      byproducts, principally oxalate, but also, under certain conditions, other TCA
      cycle acids. In addition, the bioreactor technology in use for production of this
      type of biopolymer is discussed in relation to the difficulties such fluid types
      present. The potential of pneumatically agitated reactors for such production is
      evaluated, and the lack of fundamental studies on such reactors and on the
      hydrodynamics and mixing behavior of such complex fluids is pointed out.

PMID- 8856962
TI  - Developments in biotechnological research in Austria.
AB  - Austria is a small European country with a small number of universities and
      biotechnological industries, but with great efforts in the implementation of
      environmental consciousness and corresponding legal standards. This review
      attempts to describe the biotechnological landscape of Austria, thereby focusing
      on the highlights in research by industry, universities, and research
      laboratories, as published during 1990 to early 1995. These will include
      microbial metabolite (organic acids, antibiotics) and biopolymer
      (polyhydroxibutyrate, S-layers) production; enzyme (cellulases, hemicellulases,
      ligninases) technology and biocatalysis; environmental biotechnology; plant
      breeding and plant protection; mammalian cell products; fermenter design; and
      bioprocess engineering.

PMID- 8856963
TI  - Wolbachia: intracellular manipulators of mite reproduction.
AB  - Cytoplasmically transmitted Wolbachia (alpha-Proteobacteria) are a group of
      closely related intracellular microorganisms that alter reproduction in
      arthropods. They are found in a few isopods and are widespread in insects.
      Wolbachia are implicated as the cause of parthenogenesis in parasitic wasps,
      feminization in isopods and reproductive (cytoplasmic) incompatibility in many
      insects. Here we report on the widespread occurrence of Wolbachia in spider mites
      and predatory mites based on a PCR assay for a 730 bp fragment of the ftsZ gene
      with primers that are specific for Wolbachia. An additional PCR, using two primer
      pairs that amplify a 259 bp region of the ftsZ gene that are diagnostic for the
      two Wolbachia subdivisions A and B, showed that infected mites only carried type
      B and not type A Wolbachia. The fact that some species tested negative for
      Wolbachia does not mean that the entire species is uninfected. We found that
      natural populations of Tetranychus urticae are polymorphic for the infection. The
      possible effects of Wolbachia on mite reproduction and post-zygotic reproductive
      isolation are discussed.

PMID- 8856964
TI  - Sex ratio characteristics in Ixodes rubicundus (Acari:Ixodidae), the Karoo
      paralysis tick.
AB  - The sex ratio is an important parameter which characterizes the state and
      dynamics of natural populations of animals. Although ixodid ticks are specialized
      ectoparasites, most species are bisexual and are characterized by a 1:1 sex ratio
      for their progeny. In natural populations and even in laboratory colonies, biased
      sex ratios are often observed. Ixodes rubicundus, the Karoo paralysis tick,
      parasitizes domestic stock and wild ungulates in South Africa. Adults quest from
      vegetation, can mate off or on the host and males are seldom parasitic. We
      hypothesized that the sex ratio for I. rubicundus would be 1:1 when observed
      directly in the progeny but that it would be strongly biased towards females in
      samples of parasitic adults. The results mostly supported the hypothesis but it
      was also shown that unexplained and unpredictable variations can occur. On hosts,
      females dominated strongly, except on adult angora goats where the sex ratio was
      biased in favour of the males. This disparity may be related to a greater
      retention of males in the coarse, curly hair of angora goats compared to the
      other hosts. Monthly variations in the sex ratios of the tick on hosts are
      believed to be related to the large fluctuations in sex ratios of questing ticks.

PMID- 8856965
TI  - Stress-inducible cellular responses. Introduction.

PMID- 8856966
TI  - Normal protein folding machinery.
AB  - A highly conserved protein folding machine has been maintained in the cytosol of
      both prokaryotic and eukaryotic organisms and in eukaryotic mitochondria.
      Homologous components of this machinery have also been identified in other
      organelles such as the endoplasmic reticulum in which HSP70 and DnaJ-like
      homologs reside. The high degree of conservation presumably reflects the
      proficiency with which these molecules have evolved to mediate the folding of
      proteins to their native functional states.

PMID- 8856967
TI  - Roles for hsp70 in protein translocation across membranes of organelles.
AB  - The family of hsp70 molecular chaperones plays an essential and diverse role in
      cellular physiology. Hsp70 proteins appear to elicit their effects by interaction
      with polypeptides that present domains which exhibit non-native conformations at
      distinct stages during their life in the cell. Work pertaining to the functions
      of hsp70 proteins in driving protein translocation across membranes is reviewed
      herein. Hsp70 proteins function to deliver polypeptides to protein translocation
      channels, unfold polypeptides during transit across membranes and drive the
      translocation process. All these reactions are facilitated in an ATP-dependent
      reaction cycle with the assistance of different partner proteins that modulate
      the function of hsp70.

PMID- 8856968
TI  - Protein folding and assembly in the endoplasmic reticulum.
AB  - The newly synthesized protein emerging through the ER membrane enters a unique
      environment for folding and assembly. Unlike the cytosol, the ER provides an
      oxidizing environment, has high levels of calcium, and contains enzymes for N
      linked glycosylation. The growing nascent polypeptide chain is in many cases
      modified co-translationally with N-linked sugars and begins to fold while still
      attached to the ribosome. Disulfide bond formation stabilizes the tertiary
      structure of the protein. The in vivo folding and assembly of nascent proteins
      requires a delicate balance between allowing folding to occur and preventing
      incorrect interactions that would ultimately lead to improper folding and/or
      aggregation. In the past several years, two groups of proteins that interact
      transiently with incompletely folded and assembled proteins in the ER have been
      identified and characterized. The first group consists of enzymes that promote or
      stabilize protein folding. The second is composed of proteins termed "molecular
      chaperones" that bind transiently to nascent polypeptides and apparently prevent
      misfolding by masking those regions that could lead to incorrect interactions
      between protein domains or aggregation.

PMID- 8856969
TI  - Involvement of molecular chaperones in intracellular protein breakdown.
AB  - In all cells and organelles, there exist multiple molecular chaperones, which not
      only can facilitate the proper folding, transport and assembly of multimeric
      structures, but also appear to function in intracellular protein degradation.
      Recent findings in E. coli indicate that the major chaperones of the Hsp70 (DnaK)
      and Hsp60 (GroEL) families and their cofactors (DnaJ, GrpE or GroEL and Trigger
      Factor) associate with certain short-lived proteins (e.g. mutant polypeptides or
      regulatory proteins) and promote their degradation by the ATP-dependent
      proteases, La (lon or ClpP). Moreover, ATPases of ClpA/B family not only function
      in ATP-dependent proteolysis in association with the Clp protease, but by
      themselves can facilitate or act as chaperones in protein assembly. In
      eukaryotes, Hsp70 and their cofactors, the DnaJ homologs, are essential for the
      ubiquitination of certain abnormal and regulatory proteins and in the breakdown
      of certain polyubiquitinated polypeptides by 26S proteasome. It is likely that
      the chaperones function in proteolysis either as elements that faciliate the
      recognition of unfolded proteins or that the chaperones partially unfold
      substrates to make them more susceptible to proteases or ubiquitinating enzymes.

PMID- 8856970
TI  - Molecular chaperoning of steroid hormone receptors.
AB  - The study of the large, unactivated form of steroid receptors has led to the
      discovery of an hsp90/hsp70-based multicomponent protein folding system(s). For
      steroid receptors, the hsp90 chaperone system determines both repression of
      transcriptional activity in the absence of hormone and the proper folding of the
      hormone binding domain to produce the steroid binding conformation. Like steroid
      receptors, a number of other regulators of transcription and some protein kinases
      are now known to be associated with hsp90. Given the abundance of the proteins
      comprising the hsp90 chaperone system and the apparent ubiquity of the system in
      the animal and plant kingdoms, this system is thought to serve a fundamental role
      for protein folding, function and possibly trafficking within the cytoplasm and
      nucleus. In this chapter, we discuss the work on steroid receptor heterocomplex
      composition that has led to the discovery of new chaperone proteins and we
      summarize the mechanistic information developed in cell-free studies of receptor
      heterocomplex assembly.

PMID- 8856971
TI  - Protein disulfide isomerase: a multifunctional protein of the endoplasmic
      reticulum.
AB  - Protein disulfide isomerase (PDI) is a resident enzyme of the endoplasmic
      reticulum (ER) that was discovered over three decades ago. Contemporary
      biochemical and molecular biology techniques have revealed that it is present in
      all eukaryotic cells studied and retained in the ER via a -KDEL or -HDEL sequence
      at its C-terminus. However, evidence is accumulating that in certain cell types,
      PDI can be found in other subcellular compartments, despite possessing an intact
      retention sequence. A wide range of studies has established that in presence of a
      redox pair, PDI acts catalytically to both form and reduce disulfide bonds,
      therefore acting as a disulfide isomerase. Recent studies have focused on the
      mechanism of the isomerization process and the precise role of the two active
      site sequences (-CGHC-) in the process. In addition, prokaryotes have been shown
      to possess a set of proteins that function in a similar fashion, being able to
      generate disulfide bonds on polypeptides translocated into the periplasmic space.
      Following the recent discovery that PDI binds peptides, coupled with earlier
      findings that PDI is a subunit of at least two enzymatic complexes (prolyl 4
      hydroxylase and microsomal triglyceride transfer protein), it seems that it may
      serve functions other than merely that of a disulfide isomerase. In fact, it is
      now clear that PDI can facilitate protein folding independently of its disulfide
      isomerase activity. A major challenge for the future is to define mechanistically
      how it accomplishes isomerization and the relationship between this process and
      the protein folding steps that culminate in the final, fully mature protein.

PMID- 8856972
TI  - Sensing stress and responding to stress.
AB  - Heat shock protein gene expression is enhanced by proteotoxic stress, i.e., by
      conditions favoring protein unfolding. This upregulation of heat shock protein
      genes is mediated by heat shock transcription factor HSF1. A mechanism, the
      details of which are still elusive, senses adverse conditions and causes HSF1 to
      oligomerize and to acquire DNA-binding ability. The DNA-binding form of HSF1 then
      undergoes further conformational changes that render it transcriptionally
      competent. The current model in which heat shock protein 70 acts both as sensor
      of stress and as negative regulator of HSF1 oligomerization as well as
      alternative models involving additional protein factors are discussed.

PMID- 8856973
TI  - The transcriptional regulation of heat shock genes: a plethora of heat shock
      factors and regulatory conditions.
AB  - The inducible regulation of heat shock gene transcription is mediated by a family
      of heat shock factors (HSF) that respond to diverse forms of physiological and
      environmental stress including elevated temperature, amino acid analogs, heavy
      metals, oxidative stress, anti-inflammatory drugs, arachidonic acid, and a number
      of pathophysiological disease states. The vertebrate genome encodes a family of
      HSFs which are expressed ubiquitously, yet the DNA binding properties of each
      factor are negatively regulated and activated in response to specific conditions.
      This chapter will discuss the regulation of the HSF multi-gene family and the
      role of these transcriptional activators in the inducible expression of genes
      encoding heat shock proteins and molecular chaperones.

PMID- 8856974
TI  - Transcriptional regulation of stress-inducible genes in procaryotes.
AB  - In procaryotes such as Escherichia coli, transcriptional activation of heat shock
      genes in response to elevated temperature is caused primarily by transient
      increase in the amount of sigma 32 (rpoH gene product) specifically required for
      transcription from the heat shock promoters. The increase in sigma 32 level
      results from increased translation of rpoH mRNA and from stabilization of sigma
      32 which is ordinarily very unstable. Some of the factors and cis-acting elements
      that constitute the complex regulatory circuits have been identified and
      characterized, but detailed mechanisms as well as nature of sensors and signals
      remain to be elucidated. Whereas this "classical" heat shock regulon (sigma 32
      regulon) provides major protective functions against thermal stress, a second
      heat shock regulon mediated by sigma E (sigma 24) encodes functions apparently
      required under more extreme conditions, and is activated by responding to
      extracytoplasmic signals. These regulons mediated by minor sigma factors (sigma
      32 in particular) appear to be conserved in most gram-negative bacteria, but not
      in gram-positive bacteria.

PMID- 8856975
TI  - The impact of oxidative stress on eukaryotic iron metabolism.
AB  - The processes of iron uptake and distribution are highly regulated in mammalian
      cells. Expression of the transferrin receptor is increased when cells are iron
      depleted, while expression of the iron sequestration protein ferritin is
      increased in cells that are iron-replete. Regulation of expression of proteins of
      iron uptake (transferrin receptor) and iron sequestration (ferritin) presumably
      ensures that levels of reactive free iron are not high in cells. Formation of
      reactive oxygen species occurs when free iron reacts with oxygen, and tight
      regulation of iron metabolism may enable cells to avoid engaging in destructive
      chemical reactions. Levels of intracellular iron are directly sensed by two iron
      sensing proteins. Iron regulatory protein 1 (IRP1) is a bifunctional protein; in
      cells that are iron-replete, IRP1 contains an iron-sulfur cluster and functions
      as cytosolic aconitase. In cells that are iron-depleted, IRP1 binds stem-loop
      structures in RNA transcripts known as iron responsive elements (IREs). Iron
      regulatory protein 2 (IRP2) binds similar stem-loop structures, but the mode of
      regulation of IRP2 is different in that IRP2 is rapidly degraded in iron-replete
      cells. The post-transcriptional regulation of genes of iron metabolism in
      mammalian cells ensures that cells have an adequate supply of iron, and also
      ensures that cells do not generate excess reactive oxygen species through the
      interaction of free iron and oxygen.

PMID- 8856976
TI  - Heat-shock induced protein modifications and modulation of enzyme activities.
AB  - Upon heat stress, the cell physiology is profoundly altered. The extent of the
      alterations depends on the severity of the stress and may lead to cell death. The
      heat shock response is an array of metabolic changes characterized by the
      impairment of major cellular functions and by an adaptative reprogramming of the
      cell metabolism. The enhanced synthesis of the HSPs is a spectacular
      manifestation of this reprogramming. Numerous post translational modifications of
      proteins occur in response to heat stress and can be related to altered cellular
      functions. Some proteins are heat-denatured and temporarily inactivated. Heat
      denaturation is reversible, chaperones may contribute to the repair. The extent
      of heat-denaturation depends on the cell metabolism: (a) it is attenuated in
      thermotolerant cells or in cells overexpressing the appropriate chaperones (b) it
      is enhanced in energy-deprived cells. Covalent modifications may also rapidly
      alter protein function. Changes in protein glycosylation, methylation,
      acetylation, farnesylation, ubiquitination have been found to occur during
      stress. But protein phosphorylation is the most studied modification. Several
      protein kinase cascades are activated, among which the various mitogen activated
      protein kinase (MAP kinase) cascades which are also triggered by a wide range of
      stimuli. As a possible consequence, stress modifies the phosphorylation status
      and the activity of components from the transcriptional and translational
      apparatuses. The same kinases also target key enzymes of the cellular metabolism.
      Protein denaturation results in constitutive hsp titration, this titration is a
      signal to trigger the heat-shock gene transcription and to activate some of the
      protein kinase cascades.

PMID- 8856977
TI  - SOS response as an adaptive response to DNA damage in prokaryotes.
AB  - Escherichia coli possesses an elaborate adaptive mechanism called the "SOS
      response" to cope with various types of DNA damage. More than 20 SOS genes, most
      of which are known to be involved in the functions that promote the survival of
      DNA-damaged cells, are induced by treatments that damage DNA or inhibit DNA
      synthesis. All the SOS genes share similar sequences in the regulatory regions
      called the "SOS box", to which LexA repressor binds to repress the transcription
      in the absence of DNA damage. The SOS signal appears to be the single-stranded
      DNA produced in vicinity of DNA damage, to which RecA protein binds to be
      activated as a coprotease. The activated RecA promotes autocleavage of LexA
      protein by allosteric interaction, which activates the latent serine protease
      activity of LexA. The induced products of the SOS genes repair DNA lesions by
      various mechanisms, including recombination, excision repair and error-prone
      repair, and as the consequence, the SOS signal in the cell decreases and the
      repression of the SOS genes is restored.

PMID- 8856978
TI  - Transcriptional regulators of oxidative stress-inducible genes in prokaryotes and
      eukaryotes.
AB  - It appears that redox regulation is an important mechanism for the control of
      transcription factor activation. The role of oxidation-reduction is probably
      determined in part by the structure of the transcription factors. For example,
      the presence of cysteine residues within the DNA binding sites may sensitize a
      transcription factor to ROS. The ROS-mediated regulation of transcription factors
      is specific, some ROS are more efficient than other ROS in activating defined
      regulators. While the protective antioxidant responses induced by ROS in
      prokaryotes and eukaryotes are rather conserved (for example, SOD, HSP...), the
      regulators for these genes do not appear to be conserved. Further studies
      designed to fully characterize these regulators and understand the subtle
      mechanisms involved in redox gene regulation are ongoing, and should provide the
      theoretical basis for clinical approaches using antioxidant therapies in human
      diseases in which oxidative stress is implicated.

PMID- 8856979
TI  - UV activation of mammalian stress proteins.
AB  - Ultraviolet radiation may be divided into the non-solar UVC region, the solar UVB
      (290-320 nm) region which is strongly absorbed by nucleic acids, and the solar
      UVA (320-380 nm) region which is less strongly absorbed by nucleic acids and
      proteins but causes a variety of oxidative events. As a consequence of these
      different properties, UVC/UVB radiations induce an array of stress proteins quite
      distinct from those induced by UVA radiations. Although many studies with UVC and
      UVB radiations involve lethal doses, it is clear that these radiations have the
      property of mimicking growth factor responses and stimulate various signal
      transduction pathways that lead to gene activation including transcriptional
      activation of the jun and fos proto-oncogenes. Furthermore, UVB irradiation of
      skin, at physiologically relevant doses can increase the levels of various stress
      proteins including ornithine decarboxylase, various cytokines, the p53 tumor
      suppressor protein and to a limited extent, nuclear oncogene products. Non
      cytoxic exposures of UVA radiation can lead to the up-regulation of several genes
      including collagenase, heme oxygenase 1, a specific protein phosphatase (CL 100)
      and phospholipases. At least for heme oxygenase 1, there is evidence that the
      alteration may be involved in a pathway of defense against oxidative stress.
      However, much information is lacking in the quest to build up a complete picture
      of the physiological and pathological significance of the many UV inducible
      stress responses reported.

PMID- 8856980
TI  - Signaling events controlling the molecular response to genotoxic stress.
AB  - Recently, much progress has been made in defining the signal transduction
      pathways mediating the cellular response to genotoxic stress. Multiple pathways
      involving several distinct MAP kinases (ERK, JNK/SAPK, and p38/HOG1) as well as
      the tumor suppressor protein p53 contribute to the response; the various pathways
      being differentially activated by particular genotoxic agents. Although both DNA
      damage and extranuclear events are important in initiating the response, recent
      evidence suggests the response is controlled primarily through events occurring
      at the plasma membrane, overlapping significantly with those important in
      initiating mitogenic responses. Attenuation of the responses appears to be
      largely controlled through feedback mechanisms involving gene products produced
      during the activation process.

PMID- 8856981
TI  - Mammalian DNA repair responses and genomic instability.
AB  - A cell responds to damage to its DNA in one of three ways: by tolerating the
      damage, by repairing the damage or by undergoing apoptosis. The latter two
      responses represent defenses against genomic instability and tumorigenesis
      resulting from unrepaired damage. There are multiple DNA repair pathways to cope
      with a variety of damage reflecting the importance of DNA repair in maintaining
      both cell viability and genomic stability. These include base excision repair,
      mismatch repair, double-strand break repair and nucleotide excision repair.
      Several signal transduction pathways are activated by DNA damage resulting in
      cell-cycle arrest. Cell-cycle arrest increases the time available for DNA repair
      before DNA replication and mutation fixation. Recently, there has been tremendous
      progress in our understanding of the molecular components repair processes and to
      examine recently observed interactions between DNA repair, signal transduction
      pathways and other cellular processes such as cell-cycle control, transcription,
      replication and recombination.

PMID- 8856982
TI  - Toxic metal-responsive gene transcription.
AB  - Metals play a dual role in biological systems, serving as essential co-factors
      for a wide range of biochemical reactions yet these same metals may be extremely
      toxic to cells. To cope with the stress of increases in environmental metal
      concentrations, eukaryotic cells have developed sophisticated toxic metal sensing
      proteins which respond to elevations in metal concentrations. This signal is
      transmitted to stimulate the cellular transcriptional machinery to activate
      expression of metal detoxification and homeostasis genes. This review summarizes
      our current understanding of the biochemical and genetic mechanisms which
      underlie cellular responses to toxic metals via metalloregulatory transcription
      factors.

PMID- 8856983
TI  - Tumor necrosis factor and lymphotoxin: protection against oxidative stress
      through induction of MnSOD.
AB  - Tumor necrosis factor (TNF) and lymphotoxin (LT) are related cytokines produced
      in response to infection or oxidative insults such as radiation. These cytokines
      bind to the same receptors and have pleiotropic effects on a variety of cell
      types. TNF or LT pretreatment, which can induce the synthesis of "protective"
      proteins such as mitochondrial manganese superoxide dismutase (MnSOD), protects
      animals from lethal doses of radiation or the chemotherapeutic drug doxorubicin.
      In contrast, TNF or LT pretreatment of tumor cells, which do not express MnSOD,
      results in sensitization to these insults. Therefore, radio- or chemoprotection
      of normal cells may act partially through enhanced expression of MnSOD. On the
      other hand, tumor sensitization may result from activation of "killing" proteins
      such as interleukin-1 beta converting enzyme (ICE) or other ICE-like proteases,
      possibly through TNF/LT-induced oxygen free radicals. In addition to their
      originally described anti-tumor activity, these cytokines may have new
      therapeutic indications in protecting normal cells while sensitizing tumor cells
      to radiation or chemotherapeutic drugs.

PMID- 8856984
TI  - Viral infection.
AB  - The relationship between viruses and the cellular stress response is a
      multifaceted and complex phenomenon which depends on the structural and genetic
      characteristics of the virus, on the type of infection, as well as on the
      environmental conditions. It is now well documented that infection of mammalian
      cells by several types of RNA and DNA viruses often results in alterations of the
      cellular stress response. Interactions between stress proteins and viral
      components have been described in a large variety of experimental models at
      different stages of the viral life cycle, depending on the type of virus and host
      cell. The presence of heat shock proteins in intact virions has also been
      described. On the other hand, induction of HSP expression by hyperthermia or
      other agents results in alterations of the virus replication cycle during acute
      or persistent infections of mammalian cells, and a possible role of heat shock
      proteins in the beneficial effect of fever and local hyperthermia during acute
      infection has been hypothesized. This chapter describes the different aspects of
      the interaction between viruses and the stress response, and discusses the
      possible role of stress proteins in the control of virus replication and
      morphogenesis.

PMID- 8856985
TI  - Infection, autoimmunity and autoimmune disease.
AB  - Studies of the immune response of mammals to infectious agents have revealed that
      members of the hsp60 and hsp 70 family are highly immunodominant. Given their
      high conservation during evolution this was surprising, because of the apparent
      risk of triggering of autoimmunity and autoimmune disease during the defense of a
      mammal against infection. However, detailed studies of the immune responses to
      HSP in models of autoimmune diseases in animals resulted in a change of the view
      that autoimmunity necessarily leads to autoimmune disease. It has been found that
      modulation of autoimmunity to HSP is one way to prevent autoimmune disease. At
      least in some cases even treatment of autoimmune diseases by immunization with
      heat shock protein appears feasible. This was shown in adjuvant arthritis in
      Lewis rats and insulin dependent diabetes in NOD mice. Hsp60 and hsp70 are
      ubiquitous proteins. Their involvement in regulatory loops of autoimmunity may
      serve as basis for the development of strategies, to prevent and/or treat
      autoimmune diseases even without knowledge of the causative (auto-)antigen.

PMID- 8856986
TI  - Stress proteins in inflammation.
AB  - Inflammation provides those searching in the field with a number of "models"
      allowing them to study, in vivo, in humans and in animals, the regulation and the
      functions of HSP, which are being considered as a new and promising marker for
      the severity and the prognosis of inflammatory diseases. HSP are differentially
      regulated according to the type of inflammation, whether acute or chronic,
      whether self-limiting (inflammatory cell elimination by apoptosis) or self
      perpetuating (inflammatory cell death by necrosis). We propose that mitochondria
      are a key organelle in determining the outcome of inflammation, because they are
      both the cellular "switchboard" for apoptosis and a selective target for the
      protective effects of HSP against the cytotoxic effects of TNF alpha and ROS. On
      the other hand, HSP exert multiple protective effects in inflammation, including
      self/non-self discrimination, enhancement of immune responses, immune protection,
      thermotolerance and protection against the cytotoxicity of inflammatory
      mediators. The latter protective effects against the deleterious effects of the
      mediators of inflammation, including ROS and cytokines, open new avenues for the
      development of original anti-inflammatory therapies, such as non-toxic inducers
      of a complete HS response. It may well be that the "beneficial effects of fever"
      already described by Hippocrates actually relate to increased HSP expression
      during fever, and to their protective effects....

PMID- 8856987
TI  - Attenuated heat shock transcriptional response in aging: molecular mechanism and
      implication in the biology of aging.
AB  - A characteristic feature of aging is a progressive impairment in the ability to
      adapt to environmental challenges. The purpose of this review is to present the
      experimental evidence of an attenuated heat shock transcriptional response to
      heat and physiological stresses in a number of aging mammalian model systems.
      These include the human diploid fibroblasts in culture, whole animals and animal
      derived cells and cell cultures, as well as peripheral blood mononuclear cells
      obtained from human donors. The possibility that age-dependent changes in
      cellular redox status, as exemplified by the increased production of reactive
      oxygen inter-mediates and accumulation of oxidatively-modified proteins, affects
      the regulation and function of the heat shock factor 1 (HSF1) and contributes to
      the attenuated heat shock transcriptional response in aging cells and organisms
      is discussed. Given the fundamentally important role of HSPs in many aspects of
      protein homeostasis and signal transduction, it seems likely that the inability,
      or compromised ability, of aging cells and organisms to produce HSPs in response
      to stress would contribute to the well known increase in morbidity and mortality
      of the aged when challenged.

PMID- 8856988
TI  - Stress proteins as molecular biomarkers for environmental toxicology.
AB  - Biomarkers are increasingly being used in environmental monitoring to provide
      evidence that organisms have been exposed to, or affected by, xenobiotic
      chemicals. Usually, these biomarkers rely on biochemical, histological,
      morphological, and physiological changes in whole organisms; however, changes at
      the cellular and molecular levels of organization, especially in nucleic acids
      and proteins, are increasingly being used to supplement these more traditional
      biomarkers. This chapter starts by giving a brief overview of biomarkers and some
      of the basic requirements for their effective use. Then stress-inducible proteins
      that are potentially useful as environmental biomarkers are explored, and some
      examples of their application as biomarkers and methods of detecting them are
      presented.

PMID- 8856989
TI  - Thermotolerance and heat shock proteins: possible involvement of Ku autoantigen
      in regulating Hsp70 expression.
AB  - Here we characterize and compare the phenomenon of thermotolerance and permanent
      heat resistance in mammalian cells. The biochemical and molecular mechanisms
      underlying the induction of thermotolerance, and the role that heat shock
      proteins play in its development and decay are discussed. Finally, we describe a
      novel constitutive HSE-binding factor (CHBF/Ku) that appears to be involved in
      the regulation of the heat shock response.

PMID- 8856990
TI  - Heat shock proteins as immunological carriers and vaccines.
AB  - HSPs are among the major targets of the immune response to bacterial, fungal and
      parasitic pathogens. The antigenic nature of HSPs is emphasized by evidence that
      mammals are capable of recognizing multiple B- and T cell epitopes in these
      proteins. The powerful immunological features of HSPs have led to their
      experimental use as immunomodulators and as subunit vaccine candidates.
      Mycobacterial hsp70 and hsp60 have been found to be excellent immunological
      carriers of molecules against which an immune response is desired; in the absence
      of adjuvants, the HSPs can stimulate strong and long-lasting immune responses
      against molecules which have been covalently attached to the HSPs. When used as
      subunit vaccines, HSPs derived from a variety of bacterial and fungal pathogens
      have been found to stimulate protective immunity in animal models. These studies
      suggest that HSPs might be used as immunomodulators or subunit vaccines against
      infectious disease in man.

PMID- 8856991
TI  - Regulation of thermotolerance and ischemic tolerance.
AB  - Thermotolerance and ischemic tolerance are two major biological aspects where
      heat shock (stress) proteins exert essential roles for survival in cells as well
      as in various tissues. Bioflavonoids prevent the cells from acquiring
      thermotolerance after stresses through specific inhibition in the induction of
      heat shock proteins. The mechanism of this inhibition is revealed to be due to
      the prevention of the activation of heat shock factor 1 after heat shock. The
      induction of stress proteins during the ischemic stress is then described in
      global as well as focal cerebral ischemic model in rats. The activation of heat
      shock factor 1 after ischemia is first shown to induce various stress proteins in
      the central nervous system.

PMID- 8856992
TI  - Outlook.

PMID- 8856993
TI  - Prague's season of discontent.

PMID- 8856994
TI  - Susceptibility and reactivity of sheep to Trichinella spiralis infection.
AB  - Susceptibility and reactive manifestation to Trichinella spiralis infection were
      studied in atypical hosts (sheep) for the period of 247 days. Sheep produced anti
      Trichinella antibodies as early on Day 11 (low titer 1:200), with maximum reached
      at Day 35 (titer 1:800). From Day 42 the antibody level was declining with a
      negative result of examination on Day 70. Mice exhibited anti-Trichinella
      antibodies only on Day 32 (titer 1:200). This level was rising, reaching high
      titer (1:1600) on Day 56. This antibody level persisted until Day 156. In the
      following period, a rapid decrease in the titer was observed (Graph). On Day 32,
      T. spiralis larvae in sheep were present in all groups of the muscles examined.
      The highest larval counts during the entire experiment were detected in the
      masseter. The initially high counts in the diaphragm and tongue were reduced to
      only 1/4 or 1/10 at the end of the experiment. In mice, the larvae occurred
      evenly throughout the entire experiment (Tab. I). The first appearance of a
      capsule around the T. spiralis larva in muscles was observed on Day 32 p. i. No
      cell response was detected around the capsule (Fig. 1). Neither was any response
      observed around necrotizing larvae, even though the surrounding myofibrils were
      caused to die off (Fig. 2). Certain differences in the degree of myofibril
      degradation by larvae were evident as early as on Day 32. The least damaged
      myofibrils were those in the masseter, tongue and diaphragm. This finding
      correlates with the histological recovery of a different number of necrotized
      larvae from the individual muscle groups examined. Fresh blood extravassations
      around larvae were observed on Day 59 (Fig. 3). They could be caused by the
      migration of larvae to a parasitation site. Live uncapsulated larvae were also
      found on Day 115 p. i. (Fig. 4). An increased cellular presence around some
      larvae was observed on Day 84. The larvae surrounded by lymphocytes consequently
      died off, those without lymphocytic responses formed capsules and survived (Fig.
      5). The necrotizing larvae were subject to a powerful phagocytic process,
      presented by histiocytes, forming multinuclear symplasms (Fig. 6). On Day 11 p.
      i., larvae inside a capsule were dying off as well. The initial stage of larval
      necrosis in a capsule is also accompanied by an increased lymphocytic response
      (Fig. 7). The condition of larvae in capsules and the cellular unresponsiveness
      as late as on Day 247 indicate the long-lasting viability of the larvae. The
      capsules surrounding T. spiralis larvae in mice were distinctly seen as early as
      on Day 32 p. i. Lymphocytic aggregations around the capsule were observed
      throughout the entire experiment (247 days)-Fig. 8.

PMID- 8856995
TI  - Lymphocyte blastogenesis to concanavalin A in dogs with localized demodicosis
      according to duration of clinical disease.
AB  - The aim of the study was to determine the degree of Con A induced lymphocyte
      blastogenesis in dogs with localized demodicosis (LD) within 1-3 and 6-8 weeks
      from appearance of the clinical signs. Ethidium bromide fluorescence assay was
      used for evaluation. In observation 9 clinically normal dogs, 6 dogs with LD a 4
      dogs with generalized demodicosis (GD) were used. The results showed a
      statistically significant depression (P < 0.01) of blastogenesis in the LD dogs
      in comparison with that in the healthy dogs (Fig. 1). Responses to Con A were
      normal in dogs with LD in 1-3 weeks. However, a significantly depressed response
      to Con A (P < 0.025-0.001) was demonstrated in the LD dogs in 6-8 weeks (average
      6.7 weeks) and it was comparable with that in the GD dogs with the duration of
      clinical disease on average for 8.7 weeks (Fig. 2; Tab. II). Thus,
      immunosuppression is not a necessary condition for dogs to develop spontaneous
      clinical LD and immunosuppression develops with the clinical signs of disease.

PMID- 8856996
TI  - Gender differences in the development of depression.
AB  - The present study attempted to examine possible gender differences in the
      vulnerability to depression, specifically with regard to eliciting factors,
      marital status, age of onset, season of hospitalization, and type of treatment.
      The records of all patients (67 women and 34 men), treated during 1991 for major
      depression, dysthymia, or depression NOS at a psychiatric hospital in
      Southeastern Sweden were examined, and placed in empirically derived categories
      regarding eliciting factors. The results indicated significant gender differences
      with regard to eliciting factors, marital status, and age. The eliciting factor
      in female depression was most commonly "threat to social bonds" whereas in male
      depression it was "threat to self esteem" or "threat to self respect". Married
      women were more prone to depression than were married men, as were men living
      alone compared to women living alone. Women above 60 years of age were
      significantly more prone to depression than were men of this age group. The
      results were discussed from two theoretical perspectives: gender role theory and
      gender-specific developmental theory.

PMID- 8856997
TI  - Prevalence and severity of anxiety, depression and Type A behaviors in angina
      pectoris.
AB  - The role of psychological factors in coronary heart disease was examined by
      administering the Bech Rating Scale (BRS) of mood disorders and the Jenkins
      Activity Survey (JAS) for Type A behavior patterns (TABP) to a consecutive sample
      of angina patients (N = 94), to a consecutive sample of noncardiac patients (N =
      47), and to a random sample of adults from the general population (N = 217).
      Anxiety and depression were both more frequent and more severe in angina patients
      than in noncardiac patients or in the general population. There was a tendency
      for certain components of TABP (i.e. speed, impatience, hard-driving and
      competitive disposition) to be elevated in angina patients, but a similar trend
      was noted in noncardiac patients. Although no consistent relations were observed
      between negative emotions and TABP scores in angina patients, their anxiety and
      depression scores were reliably related to their use of nitroglycerin. The
      findings concur with previous studies concerning the presence of anxiety and
      depression in patients with angina pectoris and indicate that such negative
      emotions are not closely related to Type A personality trails.

PMID- 8856998
TI  - Long-term rod dark adaptation in man. Threshold measurements, rhodopsin
      regeneration and allosteric sensitivity regulation. An evaluation.
AB  - Recent evidence strongly suggests that the relationship between threshold
      elevation (T) and fraction of bleached rhodopsin (B), obtained during a major,
      middle period of long-term rod dark adaptation in man, is well described by a
      power function, i.e., T = k.Bn, where k is a multiplicative constant and n is the
      exponent. Due primarily to the low reliability of measurements of rhodopsin
      regeneration, however, the exponent n of the power function cannot, at present,
      be given an exact value. Available information indicates that the value of the
      exponent ranges between 2.4 and 4. Implications of this uncertainty are discussed
      within the framework of the allosteric, tetrameric model of rod dark adaptation.
      It is concluded that this model in its simplest form may only offer a first
      approximation of the real system implicated in the process.

PMID- 8856999
TI  - Activity during unemployment and mental health.
AB  - The main purpose of this study was to investigate activity during unemployment
      and the relationship between such activity and mental health in a sample (n =
      213) of unemployed Norwegians. The results indicate that the unemployed are
      generally more passive than the average population, and that they are
      considerably less involved in social activities. However, the unemployed do not
      constitute a homogeneous group in terms of activity level and activity profile.
      Women were somewhat more active that men, particularly in connection with
      domestic chores. Young people were more active than the other age groups,
      particularly in connection with extra-familial activities. Several significant
      relationships were found between different activity categories and mental health.
      The more active the unemployed were, the better their mental health. The results
      are discussed in relation to similar data for the average population, other
      unemployment research, subjective and objective factors which can be of
      importance to the activity level and profile of the unemployed, sex role issues,
      theoretical models developed to explain and understand the effects of
      unemployment, methodological considerations, and the possible functions of
      activity for mental health.

PMID- 8857000
TI  - Sequencing actions: an information-search study of tradeoffs of priorities
      against spatiotemporal constraints.
AB  - How people choose between sequences of actions was investigated in an everyday
      errand-planning task. In this task subjects chose the preferred sequence of
      performing a number of errands in a fictitious environment. Two experiments were
      conducted with undergraduate students serving as subjects. One group searched
      information about each alternative. The same information was directly available
      to another group. In Experiment 1 the results showed that for two errands
      subjects took into account all attributes describing the errands, thus suggesting
      a tradeoff between priority, wait time, and travel distance with priority being
      the most important. Consistent with this finding predominantly intraalternative
      information search was observed. These results were replicated in Experiment 2
      for three errands. In addition choice outcomes, information search, and sequence
      of responding suggested that for more than two actions sequence choices are made
      in stages.

PMID- 8857001
TI  - Visual search for positional relationships between pattern elements.
AB  - The purpose of these experiments was to illustrate how a search for positional
      relationships between the elements in a stimulus pattern is effortful and serial,
      whereas a search for pattern elements (without requiring any positional
      information) takes place rapidly and in parallel. In all three experiments of
      this study, the target and distractor patterns consisted of two vertical line
      segments. In the experiment concerning the search for positional relationships
      between pattern elements, one of the line segments in a line pair had a gap, and
      the observer's task was to indicate whether the positional order of the two lines
      was identical in all the line pairs of the display, or whether the line segments
      were in a mirror-image order in one line pair (the target). In the two
      experiments concerning the search for pattern elements (no positional information
      was required), the observer's task was to look for a line pair with one gap line
      (the target) among line pairs containing two broken lines or among line pairs
      with unbroken lines. In all three tasks, the reaction time for a correct target
      detection was measured. The results showed that the search in the first task was
      highly serial, and in the second and third tasks of "feature" searches, the
      search time was nearly independent of the number of distractor pairs. It is
      suggested that this dissociation may be interpreted in the context of the quality
      of information processing in extrafoveal vision, i.e. the elements of a stimulus
      pattern can be clearly visible outside the fovca, but it is not possible to
      perceive accurately the positional relationships between them.

PMID- 8857002
TI  - Impaired tactual perception in children with Down's syndrome.
AB  - Using standardized neuropsychological tests, tactual finger discrimination,
      graphaesthesia and stereognosis were studied in a group of 11 children aged 7-11
      years with Down's syndrome (DS). All tasks were solved without visual control.
      The performance was subnormal in each test and the results of the stereognosis
      test were particularly poor. It was ascertained that the DS children could
      understand test instructions. Moreover, under visual control all objects used in
      the stereognosis test were handled correctly. The results suggest that tactual
      perception is subnormal in children with DS. The pathogenesis of the
      somatosensory abnormalities should be explored.

PMID- 8857003
TI  - Semantic distance and single cue use in category search.
AB  - Perceptual classification may be based either on the physical features of target
      and background items or on the semantic attributes of the presented items. In
      this paper we used enumeration tasks to study the role of semantic features in a
      categorial classification task. This means that subjects were asked to count the
      number of target words in a display belonging to one semantic category among a
      number of background items of other categories. Our goal was to study the
      decision logic in category search by manipulating target background conditions
      and the semantic distance between target and background classes. In the first
      experiment we found that the larger the semantic distance between targets and
      background words, the easier it was to find the targets. In the second experiment
      we found a "pop-out" effect, in which subjects could use and benefit from a
      single distinctive semantic feature, "part-likeness", in categorial
      classification. The results of the two experiments imply that the categorization
      decision logic is basically the same in physical and semantic perceptual
      classification.

PMID- 8857004
TI  - A comparison of thrombolytic therapy with primary coronary angioplasty for acute
      myocardial infarction. Myocardial Infarction Triage and Intervention
      Investigators.
AB  - BACKGROUND: Several relatively small randomized trials have shown that primary
      angioplasty results in a better short-term outcome than thrombolytic therapy in
      patients with acute myocardial infarction. These results, however, have not been
      duplicated other than in investigational trials. METHODS: We compared mortality
      during hospitalization and long-term mortality, as well as the use of resources,
      among 1050 patients in a primary-angioplasty group and 2095 patients in a
      thrombolytic-therapy group. Patients were selected from the Myocardial Infarction
      Triage and Intervention Project Registry cohort of 12,331 consecutive patients
      admitted with acute myocardial infarction to 19 Seattle hospitals between 1988
      and 1994. Because of the potential for selection bias, several subgroup analyses
      were performed that included patients eligible for thrombolysis, high-risk
      patients, and patients in the primary-angioplasty group who were treated at
      hospitals with high volumes of angioplasty. RESULTS: There was no significant
      difference in mortality during hospitalization or long-term follow-up between
      patients in the thrombolytic-therapy group and those in the primary-angioplasty
      group (mortality during hospitalization, 5.6 percent and 5.5 percent,
      respectively; P=0.93; adjusted hazard ratio for the risk of death within three
      years after primary angioplasty, 0.95; 95 percent confidence interval, 0.8 to
      1.2). There was also no significant difference in mortality between high-risk
      subgroups of patients in the two treatment groups. The rates of procedures and
      costs were lower among patients in the thrombolytic-therapy group both at the
      time of hospital discharge and after three years of follow-up (30 percent fewer
      coronary angiograms, 15 percent fewer coronary angioplasties, and 13 percent
      lower costs after three years of follow-up). CONCLUSIONS: In a community setting,
      we observed no benefit in terms of either mortality or the use of resources with
      a strategy of primary angioplasty rather than thrombolytic therapy in a large
      cohort of patients with acute myocardial infarction.

PMID- 8857005
TI  - The effects of preparations of human chorionic gonadotropin on AIDS-related
      Kaposi's sarcoma.
AB  - BACKGROUND: Kaposi's sarcoma is the most common cancer in patients with the
      acquired immunodeficiency syndrome (AIDS). Recently, certain preparations of
      human chorionic gonadotropin (hCG) have been shown to inhibit the growth of
      Kaposi's sarcoma cell lines in vitro and in immunodeficient mice. METHODS: After
      in vitro evaluation of four commercially available hCG preparations, the most
      active product was evaluated in 36 patients with AIDS-related Kaposi's sarcoma.
      In a phase 1-2 trial, 24 patients received intralesional injections of hCG three
      times a week for two weeks at doses of 250, 500, 1000, or 2000 IU (6 patients
      each). In each patient three nodular lesions were injected, two with the drug and
      one with diluent alone. In a double-blind trial, 12 additional patients were
      randomly assigned to receive intralesional injections of 2000 IU of hCG or
      diluent alone (6 patients each; two lesions per patient). At the conclusion of
      therapy, the lesions were measured, their gross appearance assessed, and biopsy
      specimens evaluated. RESULTS: A.P.L. (Wyeth-Ayerst), which had the most in vitro
      activity against Kaposi's sarcoma cell lines, was selected for the clinical
      investigation. Treatment with A.P.L. was well tolerated at all doses. In the
      cohorts given 250, 500, 1000, and 2000 IU, 1, 5, 5, and 10 of the 12 injected
      lesions responded, respectively (P=0.03 for trend). Complete tumor regression was
      observed in one lesion each at the 250-IU and 500-IU doses, in two lesions given
      the 1000-IU dose, and in five lesions given the 2000-IU dose. In the double-blind
      study, none of the 12 lesions in the six patients injected with diluent had
      responses, as compared with 10 of the 12 lesions in the six patients injected
      with hCG (P=0.015). Microscopical evidence of apoptosis was observed only in hCG
      treated lesions. The percentage of cells that died increased in a dose-dependent
      manner (P<0.001). Serum levels of follicle-stimulating hormone (P=0.002) and
      luteinizing hormone (P=0.001) declined after the last injection of hCG, but there
      was no effect on these hormones in the diluent-treated patients. CONCLUSIONS: The
      intralesional injection of hCG induces the regression of AIDS-related Kaposi's
      sarcoma lesions in a dose-dependent manner. The response of these tumors appears
      to be mediated by the induction of apoptosis.

PMID- 8857006
TI  - Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease
      Study Group.
AB  - BACKGROUND: Although the incidence of Lyme disease is highest in children, there
      are few prospective data on the clinical manifestations and outcomes in children.
      METHODS: We conducted a prospective, longitudinal, community-based cohort study
      of children with newly diagnosed Lyme disease in an area of Connecticut in which
      the disease is highly endemic. We obtained clinical and demographic information
      and performed serial antibody tests and follow-up evaluations. RESULTS: Over a
      period of 20 months, 201 consecutive patients were enrolled; their median age was
      7 years (range, 1 to 21). The initial clinical manifestations of Lyme disease
      were a single erythema migrans lesion in 66 percent, multiple erythema migrans
      lesions in 23 percent, arthritis in 6 percent, facial-nerve palsy in 3 percent,
      aseptic meningitis in 2 percent, and carditis in 0.5 percent. At presentation, 37
      percent of the patients with a single erythema migrans lesion and 89 percent of
      those with multiple erythema migrans lesions had antibodies against Borrelia
      burgdorferi. All but 3 of the 201 patients were treated for two to four weeks
      with conventional antimicrobial therapy, which was administered orally in 96
      percent. All had prompt clinical responses. After four weeks, 94 percent were
      completely asymptomatic (including the two patients whose parents had refused to
      allow antimicrobial treatment). At follow-up a mean of 25.4 months later, none of
      the patients had evidence of either chronic or recurrent Lyme disease. Six
      patients subsequently had a new episode of erythema migrans. CONCLUSIONS: About
      90 percent of children with Lyme disease present with erythema migrans, which is
      an early stage of the disease. The prognosis is excellent for those with early
      Lyme disease who are treated promptly with conventional courses of antimicrobial
      agents.

PMID- 8857007
TI  - Lung transplantation for lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis is a rare disease of unknown origin that
      usually leads to progressive deterioration of lung function and eventual death
      from respiratory failure. It occurs in women of reproductive age and people with
      tuberous sclerosis. Lung transplantation is a recent therapeutic approach.
      METHODS: We conducted a retrospective study by questionnaire of 34 patients,
      treated at 16 transplantation centers, who underwent lung transplantation for end
      stage lymphangioleiomyomatosis between 1983 and 1995. RESULTS: Of the 34
      patients, 27 received single-lung transplants; 6, bilateral transplants; and 1, a
      heart-lung transplant. As of August 31, 1995, the actuarial survival calculated
      by the Kaplan-Meier method was 69 percent after one year and 58 percent after two
      years. Eighteen patients were alive 33 +/- 20 months (range, 3 to 74) after
      transplantation. Forced expiratory volume in one second increased from 24 +/- 12
      percent of the predicted value before transplantation to 48 +/- 16 percent six
      months after transplantation. Five early deaths (within one month) were due to
      hemorrhage (in one patient), acute lung injury (in three), and dehiscence of the
      bronchial anastomosis (in one). Eleven late deaths (after one month) were due to
      infections (in eight patients), bronchiolitis obliterans (in two), and metastatic
      nephroblastoma (in one). Disease-associated problems were extensive pleural
      adhesions in 18 patients, leading to moderate-to-severe intraoperative hemorrhage
      in 4; pneumothorax in the native lung after single-lung transplantation in 6
      patients; postoperative chylothorax in 3; and recurrent lymphangioleiomyomatosis
      in the allograft in 1 patient, who died of disseminated aspergillosis.
      CONCLUSIONS: Although disease-related complications are frequent, lung
      transplantation can be a valuable therapy for patients with end-stage
      lymphangioleiomyomatosis.

PMID- 8857008
TI  - Images in clinical medicine. Consequences of cupping.

PMID- 8857009
TI  - Sex differences in academic advancement. Results of a national study of
      pediatricians.
AB  - BACKGROUND: Although the numbers of women in training and in entry-level academic
      positions in medicine have increased substantially in recent years, the
      proportion of women in senior faculty positions has not changed. We conducted a
      study to determine the contributions of background and training, academic
      productivity, distribution of work time, institutional support, career attitudes,
      and family responsibilities to sex differences in academic rank and salary among
      faculty members of academic pediatric departments. METHODS: We conducted a cross
      sectional survey of all salaried physicians in 126 academic departments of
      pediatrics in the United States in January 1992. Of the 6441 questionnaires
      distributed, 4285 (67 percent) were returned. The sample was representative of
      U.S. pediatric faculty members. Multivariate models were used to relate academic
      rank and salary to 16 independent variables. RESULTS: Significantly fewer women
      than men achieved the rank of associate professor or higher. For both men and
      women, higher salaries and ranks were related to greater academic productivity
      (more publications and grants), more hours worked, more institutional support of
      research, greater overall career satisfaction, and fewer career problems. Less
      time spent in teaching and patient care was related to greater academic
      productivity for both sexes. Women in the low ranks were less academically
      productive and spent significantly more time in teaching and patient care than
      men in those ranks. Adjustment for all independent variables eliminated sex
      differences in academic rank but not in salary. CONCLUSIONS: Lower rates of
      academic productivity, more time spent in teaching and patient care and less time
      spent in research, less institutional support for research, and lower rates of
      specialization in highly paid subspecialties contributed to the lower ranks and
      salaries of female faculty members.

PMID- 8857010
TI  - Advances in coronary angioplasty.

PMID- 8857011
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 33-1996. A 55-year-old man with a long-term tracheostomy and acid
      fast bacilli in peristomal granulations.

PMID- 8857012
TI  - Kaposi's sarcoma--what's human chorionic gonadotropin got to do with it?

PMID- 8857013
TI  - Should thrombolysis or primary angioplasty be the treatment of choice for acute
      myocardial infarction? Thrombolysis--the preferred treatment.

PMID- 8857014
TI  - Should thrombolysis or primary angioplasty be the treatment of choice for acute
      myocardial infarction? Primary angioplasty--the strategy of choice.

PMID- 8857015
TI  - Quality of health care. Part 6: The role of physicians in the future of quality
      management.

PMID- 8857016
TI  - Cardiac troponin T levels for risk stratification in acute myocardial ischemia.
      GUSTO IIA Investigators.
AB  - BACKGROUND: The prognosis of patients hospitalized with acute myocardial ischemia
      is quite variable. We examined the value of serum levels of cardiac troponin T,
      serum creatine kinase MB (CK-MB) levels, and electrocardiographic abnormalities
      for risk stratification in patients with acute myocardial ischemia. METHODS: We
      studied 855 patients within 12 hours of the onset of symptoms. Cardiac troponin T
      levels, CK-MB levels, and electrocardiograms were analyzed in a blinded fashion
      at the core laboratory. We used logistic regression to assess the usefulness of
      baseline levels of cardiac troponin T and CK-MB and the electrocardiographic
      category assigned at admission-ST-segment elevation, ST-segment depression, T
      wave inversion, or the presence of confounding factors that impair the detection
      of ischemia (bundle-branch block and paced rhythms)-in predicting outcome.
      RESULTS: On admission, 289 of 801 patients with base-line serum samples had
      elevated troponin T levels (> 0.1 ng per milliliter). Mortality within 30 days
      was significantly higher in these patients than in patients with lower levels of
      troponin T (11.8 percent vs. 3.9 percent, P < 0.001). The troponin T level was
      the variable most strongly related to 30-day mortality (chi-square = 21, P <
      0.001), followed by the electrocardiographic category (chi-square = 14, P =
      0.003) and the CK-MB level (chi-square = 11, P = 0.004). Troponin T levels
      remained significantly predictive of 30-day mortality in a model that contained
      the electrocardiographic categories and CK-MB levels (chi-square = 9.2, P =
      0.027). CONCLUSIONS: The cardiac troponin T level is a powerful, independent risk
      marker in patients who present with acute myocardial ischemia. It allows further
      stratification of risk when combined with standard measures such as
      electrocardiography and the CK-MB level.

PMID- 8857017
TI  - Cardiac-specific troponin I levels to predict the risk of mortality in patients
      with acute coronary syndromes.
AB  - BACKGROUND: In patients with acute coronary syndromes, it is desirable to
      identify a sensitive serum marker that is closely related to the degree of
      myocardial damage, provides prognostic information, and can be measured rapidly.
      We studied the prognostic value of cardiac troponin I levels in patients with
      unstable angina or non-Q-wave myocardial infarction. METHODS: In a multicenter
      study, blood specimens from 1404 symptomatic patients were analyzed for cardiac
      troponin I, a serum marker not detected in the blood of healthy persons. The
      relation between mortality at 42 days and the level of cardiac troponin I in the
      specimen obtained on enrollment was determined both before and after adjustment
      for baseline characteristics. RESULTS: The mortality rate at 42 days was
      significantly higher in the 573 patients with cardiac troponin I levels of at
      least 0.4 ng per milliliter (21 deaths, or 3.7 percent) than in the 831 patients
      with cardiac troponin I levels below 0.4 ng per milliliter (8 deaths, or 1.0
      percent; P < 0.001). There were statistically significant increases in mortality
      with increasing levels of cardiac troponin I (P < 0.001). Each increase of 1 ng
      per milliliter in the cardiac troponin I level was associated with a significant
      increase (P = 0.03) in the risk ratio for death after adjustment for the base
      line characteristics that were independently predictive of mortality (ST-segment
      depression and age > or = 65 years). CONCLUSIONS: In patients with acute coronary
      syndromes, cardiac troponin I levels provide useful prognostic information and
      permit the early identification of patients with an increased risk of death.

PMID- 8857018
TI  - Controlled trial of interleukin-2 infusions in patients infected with the human
      immunodeficiency virus.
AB  - BACKGROUND: Interleukin-2 is a cytokine that regulates the proliferation and
      differentiation of lymphocytes. In preliminary studies, intermittent infusions of
      interleukin-2 led to increases in CD4 counts in patients with human
      immunodeficiency virus (HIV) infection and more than 200 CD4 cells per cubic
      millimeter. We conducted a controlled study to evaluate the long-term effects of
      such therapy on both CD4 counts and the viral burden. METHODS: Sixty HIV-infected
      patients with base-line CD4 counts above 200 cells per cubic millimeter were
      randomly assigned to receive either interleukin-2 plus antiretroviral therapy (31
      patients, 1 of whom was lost to follow-up) or antiretroviral therapy alone (29
      patients). Interleukin-2 was administered every two months for six cycles of five
      days each, starting at a dosage of 18 million i.u. per day. Safety and
      immunologic and virologic measures were monitored monthly until four months after
      the last treatment cycle. RESULTS: In patients treated with interleukin-2, the
      mean (+/-SE) CD4 count increased from 428 +/- 25 cells per cubic millimeter at
      base line to 916 +/- 128 at month 12, whereas in the control group, the mean CD4
      count decreased from 406 +/- 29 cells per cubic millimeter to 349 +/- 41 (P <
      0.001). There were no significant differences between the groups in serial
      measurements of the plasma HIV RNA or p24 antigen concentration during the 12
      months of treatment. Constitutional symptoms (fever, malaise, and fatigue) and
      asymptomatic hyperbilirubinemia were the chief dose-limiting toxic effects of
      interleukin-2 therapy. CONCLUSIONS: In patients with HIV infection and base-line
      CD4 counts above 200 cells per cubic millimeter, intermittent infusions of
      interleukin-2 produced substantial and sustained increases in CD4 counts with no
      associated increase in plasma HIV RNA levels.

PMID- 8857019
TI  - Increased glucose transport-phosphorylation and muscle glycogen synthesis after
      exercise training in insulin-resistant subjects.
AB  - BACKGROUND: Insulin resistance in the offspring of parents with non-insulin
      dependent diabetes mellitus (NIDDM) is the best predictor of development of the
      disease and probably plays an important part in its pathogenesis. We studied the
      mechanism and degree to which exercise training improves insulin sensitivity in
      these subjects. METHODS: Ten adult children of parents with NIDDM and eight
      normal subjects were studied before starting an aerobic exercise-training
      program, after one session of exercise, and after six weeks of exercise. Insulin
      sensitivity was measured by the hyperglycemic-hyperinsulinemic clamp technique
      combined with indirect calorimetry, and the rate of glycogen synthesis in muscle
      and the intramuscular glucose-6-phosphate concentration were measured by carbon
      13 and phosphorus-31 nuclear magnetic resonance spectroscopy, respectively.
      RESULTS: During the base-line study, the mean (+/-SE) rate of muscle glycogen
      synthesis was 63 +/- 9 percent lower in the offspring of diabetic parents than in
      the normal subjects (P < 0.001). The mean value increased 69 +/- 10 percent (P =
      0.04) and 62 +/- 11 percent (P = 0.04) after the first exercise session and 102
      +/- 11 percent (P = 0.02) and 97 +/- 9 percent (P = 0.008) after six weeks of
      exercise training in the offspring and the normal subjects, respectively. The
      increment in glucose-6-phosphate during hyperglycemic-hyperinsulinemic clamping
      was lower in the offspring than in the normal subjects (0.039 +/- 0.013 vs. 0.089
      +/- 0.009 mmol per liter, P = 0.005), reflecting reduced glucose transport
      phosphorylation, but this increment was normal in the offspring after the first
      exercise session and after exercise training. Basal and stimulated insulin
      secretion was higher in the offspring than the normal subjects and was not
      altered by the exercise training program. CONCLUSIONS: Exercise increases insulin
      sensitivity in both normal subjects and the insulin-resistant offspring of
      diabetic parents because of a twofold increase in insulin-stimulated glycogen
      synthesis in muscle, due to an increase in insulin-stimulated glucose transport
      phosphorylation.

PMID- 8857020
TI  - Intrauterine growth retardation and postnatal growth failure associated with
      deletion of the insulin-like growth factor I gene.

PMID- 8857021
TI  - Images in clinical medicine. Traumatic carotid-artery dissection.

PMID- 8857022
TI  - Costimulatory B7 molecules in the pathogenesis of infectious and autoimmune
      diseases.

PMID- 8857023
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 34-1996. A 50-year-old woman with cardiac disease, an electronic
      pacemaker, and cardiac arrest in ventricular fibrillation.

PMID- 8857024
TI  - Cardiac troponins in acute coronary syndromes.

PMID- 8857025
TI  - Insulin-like growth factor I--an important intrauterine growth factor.

PMID- 8857026
TI  - Reform of the Veterans Affairs health care system.

PMID- 8857027
TI  - [Plasma renin activity in tachistin-stimulated hypercalcemia and under the effect
      of chlorazine].
AB  - The aim of the present study was to elucidate the correlation between the Renin
      secretion and increased Plasma Calcium concentration and the role of Calmodulin
      in this process. Plasma Renin activity was determined radioimmunologically in 31
      white rats, that were grouped as follows: group I - 7 controls loaded for 6 days
      perorally with 0.5 ml/200 g b.w. glycerin and injected i.m. for 6 days with 0.1
      ml/200 g b.w. with 0.9% NaCl; group II - 8 rats, treated for 6 days with
      Tachistin 0.0025 mg/200 g b.w., dissolved in glycerin 0.5 ml/200 g b.w.; group
      III - 5 rats, treated with Tachistin 0.005 mg/200 g b.w. in the same manner;
      group IV - 5 rats injected i.m. with Chlorazin 0.5 mg/200 g b.w. for 6 days;
      group V - 6 rats, loaded with double dose Tachistin and with Chlorazin 0.5 mg/200
      g b.w. for 6 days. Blood samples were taken intracardially on the seventh day
      from the beginning of the experiment and were analyzed with kits of Sorin
      Biomedica-Italy. Our results suggest that the hypercalcemia induced by Tachistin
      caused a dose-dependent increase of PRA and Ca-Calmodulin complex is the dominant
      second messenger of Renin secretion.

PMID- 8857028
TI  - [Morphological changes in the pancreas after ligation of the excretory duct].
AB  - The rabbit pancreatic structure at histological and ultrastructural level, in
      different intervals after ligature of pancreatic duct, was studied. Changes in
      the exo- and endocrine parenchyma were observed. Canalicular structures and
      conjunctive tissue replace the destroyed acinar cells. In some of the islets the
      B cells are degranulated or necrotic. Some islets contain infiltrations of
      lymphocytes, macrophages and granulocytes. Cavities formed by necrotic endocrine
      cells could appear. The A and B cells proliferation is observed in the new-formed
      clusters of endocrine cells and ductless. The mechanism of this process is
      similar to that of the islet formation during the embryonic development or in
      nesidioblastosis, but they are never transformed in the definitive islet of
      Langerhans.

PMID- 8857029
TI  - [The role of a growth-related cytosol protein kinase in the pathogenesis of
      psoriasis].
AB  - A Growth-related protein kinase's activity was studied in clinically affected and
      unaffected psoriatic epidermis. This activity was about 3 fold higher in
      clinically affected skin. Additionally, the unaffected psoriatic epidermis shows
      higher activity than the normal one. We conclude that the Growth-related protein
      kinase might be involved in the pathogenesis of psoriasis.

PMID- 8857030
TI  - [The ultrastructural changes in type-2 pneumocytes in experimental heat and
      endotoxic shock].
AB  - The early ultrastructural changes in type 2 pneumocytes (PN2) as a result of burn
      and endotoxic shock in rats and rabbits were studied. Stereotype morphological
      damages in PN2 were established. Differences between experimental models were
      quantitative and depend mainly from the severity of shock and animals species.
      Morphofunctional heterogenity of PN2 population leads to the appearance of three
      groups of PN2: 1) PN2 with degenerative changes; 2) PN2 with "stress"
      hyperactivity and exocytosis of lamelar bodies; and 3) PN2 with increased number
      of lamelar bodies. Disturbances of lamelar bodies morphogenesis (conglomerates,
      giant lamelar bodies) as well as lamelar bodies formation by alternative way -
      directly from rough endoplasmic reticulum were observed. The predominant part of
      the described PN2 lesins were adaptive in character.

PMID- 8857031
TI  - [The morphological characteristics of the pit cells in the rat liver after the
      use of the glycopeptide preparation Polyerga].
AB  - Pit cells are morphological equivalent of large granular lymphocytes with NK
      activity. The aim of our study is to define the morphological changes of pit
      cells in the liver of the rat after stimulation with the biological response
      modifier Polyerga. Polyerga was applied intramuscularly in a single dose of 6 mu
      g per kg body weight. The animals were perfused on the 24-th hour, 48-th hour, on
      the 4-th day and on the 7-th day after injection. The perfusion was done through
      the portal vein and the liver was processed for electron microscopical
      cytochemistry for endogeneous peroxidase demonstration. A 3-to-4-fold increase in
      the number of pit cells was observed within a period of 1 to 4 days after
      injection. Pit cell granules were negative for endogeneous peroxidase. After
      Polyerga stimulation pit cells showed a tendency of orientation of their
      organelles toward the contact area with Kupffer and endothelial cells. These
      changes are considered to represent the morphological expression of rat liver pit
      cell activation.

PMID- 8857032
TI  - [The effect of erythropoietin on megakaryocytopoiesis depressed by dialysable
      substances in experimental animals].
AB  - The aim of the study is to examine influence of r-Hu-Ero on megakaryocytopoiesis
      in rats with depressed by dialysable substances thrombocytopoiesis. Experimental
      animals are male Wistar rats, treated with bidestilled water, used dialysis
      solution and r-Hu-Ero. We investigate bone marrow of experimental rats. More
      expressed increase of megakaryocyte count "pro mile" in rats with depressed
      megakaryocytopoiesis, as well as influence on megakaryocyte maturation for
      shorter period of time, provide evidence to be accepted that
      megakaryocytopoiesis, depressed by dialysable substances is more sensitive to
      stimulating effect of r-Hu-Ero. The reason for this enhanced sensitivity at
      present appear unclear.

PMID- 8857033
TI  - [The genotoxicity and carcinogenic potential of gastrofenzin].
AB  - Genotoxicity of the Bulgarian drug gastrophensin was studied by using a battery
      of two genotoxicity assays "in vitro" - Salmonella/mutation assay and "in vivo" -
      the rodent bone marrow micronucleus test. Mutagenicity of water solution of
      gastrophensin towards Salmonella "in vitro" - the rodent bone marrow micronucleus
      test. Mutagenicity of water solution of gastrophensin towards Salmonella "in
      vitro" was tested in five mutant, histidine auxotrophic strains - TA 1535, TA
      1537, TA 1538, TA 98 and TA 100 without and in the presence of metabolic
      activation (+/- S9) at concentration of 0.4, 2 and 10 mg center dot ml-1.
      Gastrophensin did not induce mutagenic response in the Salmonella/mutation assay
      in a range of tested concentrations in both series of assays (+/- S9).
      Gastrophensin did not induce micronuclei in bone marrow cells of male C57Bl6 mice
      at 24, 48 and 72 hours after single oral treatment with 236 mg center dot kg-1
      (80% DL50 oral, mice) and 118 mg center dot kg-1 (40% DL50 oral, mice). Based on
      the present data a conclusion of the lack of mutagenicity and of carcinogenic
      potency of gastrophensin was made.

PMID- 8857034
TI  - [The relationship between resorption and the morphological changes in the gastric
      mucosa of rats after acute and chronic exposures to acetylsalicylic acid].
AB  - The effect of acute and chronic ASA administration on stomach and duodenal mucosa
      was studied on white male Wistar rats. ASA (250 mg/kg b.w.) was administered by
      esophageal intubation in a single dose, and the rats were sacrificed at 2, 6, 24
      hours, or after two, three, ten and twenty days, 24 hours after the last ASA
      application. Two types of erosions were found in the first 24 hours: superficial
      and deep. Superficial erosions showed advanced healing by the 24th hour. Deep
      erosions appearing between 6 and 24 hours from the beginning of experiment became
      deeper, after two and three days ASA application. They had morphological features
      of chronic ones by the 10-20th day. ASA resorbtion was most expressed by the 3rd
      day from the experimental onset (plasma concentration 0.348 +/- 0.052 g/l). The
      resorbtion was decreased in chronic experiment, and plasma concentration (0.236
      +/- 0.046 g/l, 0.244 +/- 0.045 g/l) showed statistically reliable lower values.

PMID- 8857036
TI  - Conquering the common cough with ayurveda.

PMID- 8857035
TI  - Physical mapping of several heat-shock genes in Pseudomonas aeruginosa and the
      cloning of the mopA (GroEL) gene.
AB  - Using a series of oligonucleotides synthesized on the basis of conserved
      nucleotide or amino acid motifs in heat-shock genes/proteins, we have physically
      mapped the dnaK, lon, and hptG genes of Pseudomonas aeruginosa. Hybridization
      data suggest that there is a single copy of the mopBA (GroES/GroEL) operon but
      several additional copies of mopA. In addition, the map coordinates for the rpoD,
      rpoS, and rpoH genes were determined. The mopA gene from the mopBA operon was
      cloned and sequenced. The protein product of this gene showed 79% amino acid
      identity to the Escherichia coli GroEL and 98% identity to the GroEL sequence
      from P. aeruginosa ATCC 27853. A number of discrepancies were found with the
      latter sequence.

PMID- 8857037
TI  - Vagotomy in India.

PMID- 8857038
TI  - Truncal vagotomy and gastrojejunostomy for chronic duodenal ulcer in India.
AB  - BACKGROUND: Insufficient information is available on long term results of truncal
      vagotomy and gastrojejunostomy since most previous series have relied on
      functional grading using the Visick scale which possibly both overdiagnoses and
      underdiagnoses complications. We used endoscopy to assess the results following
      truncal vagotomy and gastrojejunostomy as well as functional grading and compared
      them with published results of highly selective vagotomy. METHODS: Two hundred
      patients were reviewed (5-11 years after truncal vagotomy and gastrojejunostomy)
      by clinical examination and endoscopy. Completeness of vagotomy was assessed by
      estimation of the postprandial alkaline tide in the urine and gall bladder using
      ultrasonography. RESULTS: The ulcer recurrence rate was 15 (7%). Nine (60%) of
      the recurrent ulcers were asymptomatic and detected only on endoscopy. In all
      patients with recurrence, the urinary alkaline tide estimation revealed an
      incomplete vagotomy. Dumping was present in 12%, it was troublesome in 4%,
      occasional episodes of post-vagotomy diarrhoea in 6% (all in Visick grades I or
      II) and bile vomiting in 17% (affecting the lifestyle in only 5%). Recurrence and
      other complications were not related to the experience of the operating surgeon
      or the type of gastroenterostomy. There was no mortality. Overall, satisfactory
      long term functional results (Visick grades I and II) were found in 8% of
      patients. CONCLUSIONS: Truncal vagotomy and gastrojejunostomy still remains the
      best option in the surgical management of chronic duodenal ulcer. Long term
      results are good with a relatively low incidence of troublesome complications.

PMID- 8857039
TI  - The quality of prescribing in an Indian district.
AB  - BACKGROUND: There has been no previous broad-based study in India which analyses
      the rationality of prescriptions in relation to the diseases for which they are
      given. We performed such an analysis in a representative district of Maharashtra.
      METHODS: During 1993, 3582 prescriptions of a district-level stratified purposive
      sample of 49 doctors from the Satara district in Maharashtra were assessed. The
      prescriptions were collected prospectively from the outdoor clinics of these
      doctors from widely varying health sectors--private practice, government
      employment, differing educational qualifications and diverse socio-economic zones
      and geographic locations. With the help of Prescription Analysis Guidelines
      (PAGs) and a scoring system developed for this study, these prescriptions were
      compared with standard prescriptions, and were ranked on a quantitative
      rationality scale. The rationality scores of various categories of doctors were
      then compared. RESULTS: The average score per prescription was 14.2 out of 30.
      The score increased significantly with educational qualification. The use of
      drugs was irrational in 19% of prescriptions, unnecessary in 47% and hazardous in
      11%. Unnecessary injections were given in 24% of cases. Prescriptions given by
      doctors working in the public sector were significantly better than those given
      by private sector doctors in all respects, except for the use of unnecessary
      injections. CONCLUSIONS: Overall, the quality of prescriptions, especially in the
      private sector is low with a high prevalence of undesirable drug use.

PMID- 8857040
TI  - Preoperative bile salt administration versus bile refeeding in obstructive
      jaundice.
AB  - BACKGROUND: Endotoxaemia due to intraluminal bile salt depletion may be a cause
      of renal failure in patients with obstructive jaundice. Administration of bile
      salts to these patients has been reported to decrease portal and systemic
      endotoxaemia during surgery and improve renal function. However, such changes
      have not been shown with bile refeeding. We compared the effect of preoperative
      bile salt administration with preoperative bile refeeding on renal function in
      patients with obstructive jaundice. METHODS: Sixteen patients with obstructive
      jaundice underwent percutaneous transhepatic biliary drainage--eight received
      oral bile salts (500 mg of sodium deoxycholate 8-hourly for 48 hours
      preoperatively) and the other 8 were refed the total bile output for the entire
      period of biliary drainage (median 13 days). Blood endotoxin levels and renal
      function were assessed before, during and after the operation. RESULTS: The
      number of patients with intraoperative portal and postoperative systemic
      endotoxaemia decreased after both forms of therapy. Renal function also improved
      in both the groups--all 4 patients with renal failure recovered. There was a
      significant increase in creatinine clearance postoperatively after bile salt
      therapy (from 65 ml/minute preoperatively to 87 ml/minute postoperatively).
      CONCLUSION: Refeeding of bile obtained by percutaneous catheter drainage is an
      effective, cost-free substitute for oral bile salts in patients with obstructive
      jaundice.

PMID- 8857042
TI  - Prevention of gastrointestinal diseases.
AB  - The prevalence of gastrointestinal diseases markedly differs between developed
      and developing countries because of the poor sanitation, hygiene, impure water
      and food ingestion, widespread illiteracy and poverty in the developing world.
      The incidence of gastrointestinal diseases such as diarrhoea, cholera, typhoid,
      dysentery, viral hepatitis (A and E virus) can be substantially reduced by
      providing clean water and food to the population. Restricting consumption of
      tobacco and nonsteroidal anti-inflammatory drugs will reduce diseases and/or
      complications of the upper gastrointestinal tract. Diminishing alcohol intake and
      overuse of blood transfusion and improving blood banks would prevent many acute
      and chronic liver diseases. Costly passive and active immunoprophylaxis will
      become unnecessary if these measures are undertaken.

PMID- 8857041
TI  - Prenatal diagnosis of beta-thalassaemia mutations using the reverse dot blot
      technique.
AB  - BACKGROUND: Beta-thalassaemia is the most common genetic disorder among Indians
      and a number of mutations causing this disease have been reported. Since
      effective treatment of thalassaemia major is complicated and very expensive,
      prenatal diagnosis has become an important option for those at risk of having an
      affected foetus. We report the use of a rapid hybridization method called
      'reverse dot blot' for detection of specific mutations of the beta-globin gene.
      METHODS: DNA was obtained from a 12-week-old foetus by chorionic villus sampling
      and was amplified using specific primers by the polymerase chain reaction and
      analysed by the reverse dot blot test. Results were available within 36 hours
      after sampling. RESULT: The father and mother were found to be heterozygous for
      codon 15 (G-A) mutation of the beta-globin gene. The foetus was normal.
      CONCLUSION: Reverse dot blot is a rapid and reliable technique for mutation
      detection in the beta-globin gene and can be useful for antenatal diagnosis.

PMID- 8857043
TI  - Urine analysis in clinical practice.

PMID- 8857044
TI  - Indo-German Multidisciplinary Symposium: Medical Ethics Today., 27-28 October
      1995, New Delhi.

PMID- 8857045
TI  - International Medical Commission, Bhopal: a model for the future.

PMID- 8857046
TI  - Tobacco--the public and the politics.

PMID- 8857047
TI  - Byssinosis.

PMID- 8857048
TI  - Antibiotic therapy in tuberculin-positive children with lung lesions.

PMID- 8857049
TI  - Doctors' awareness of CPA.

PMID- 8857050
TI  - Safe sex: does it exist?
AB  - Safe sex is alive and well. However, it is unsafe sex and the circumstances
      around it that clinicians need to identify. The difficulties in defining safe and
      unsafe sex will be described in an effort to highlight the great diversity and
      individuality that surrounds notions of safety and of sexual activity. It is
      emphasised that safe sex cannot be reduced to the use of a condom and that there
      are many complex personal, social, political, legislative and economic factors
      involved in an individual's decision to have safe sex and their ability to carry
      it out.

PMID- 8857051
TI  - Managing impotence. A general practice approach.
AB  - The burgeoning interest in men's health, together with the greater recognition
      given to the existence of erectile dysfunction, suggests that many more men will
      in future expect their family doctors to be able to deal with this problem. This
      article attempts to present options for management in practical terms that
      translate readily into actual clinical practice.

PMID- 8857052
TI  - STD screening. Practical tips.
AB  - General practitioners can contribute to community STD control by using the
      important tools of a sexual history, appropriate examination and tests. These
      screening tools allow early detection of disease, in 'high risk' people, accurate
      diagnosis of people with signs or symptoms, examination of sexual partners and
      the provision of preventive education and counselling.

PMID- 8857053
TI  - Sex and the postmenopausal woman.
AB  - Sexual behaviour is a combination of biological, psychosocial and cultural
      factors. Each factor involves particular issues and requires specific management
      for the postmenopausal woman. These will be identified and straightforward
      management discussed. A combination of counselling and hormone therapy has
      enabled those women with problems to improve their sexual activity.

PMID- 8857054
TI  - Adult survivors of childhood sexual abuse. Do I have them in my practice?
AB  - The long term sequelae of childhood sexual abuse include many symptoms commonly
      encountered in general practice settings. Guidelines to empathic history taking,
      comprehensive assessment, and an overview of management are presented, together
      with a contextual background.

PMID- 8857055
TI  - Locums. A guide on how to use them.
AB  - This article outlines a range of issues that should be resolved with each locum
      before placement in a general practice. It also provides some measures by which
      the service provided to the practice can be evaluated. Through a series of
      checklists, general practitioners can prepare their practice for locums and
      assess the impact of the service.

PMID- 8857056
TI  - The use of role plays in teaching drug and alcohol management.
AB  - This is an evaluation of the use of role plays to teach drug and alcohol
      assessment and management skills to medical students as part of their general
      practice training. Role plays of 'real life' scenarios enable students to
      evaluate their own learning experiences. This method facilitates effective peer
      discussion of clinical and ethical issues with a high degree of acceptability to
      both students and teachers.

PMID- 8857057
TI  - Integrating general practice and hospital services.
AB  - OBJECTIVES: To evaluate a model of negotiations between six Divisions of General
      Practice and four teaching hospitals, aimed at creating formal agreements to
      improve the GP-hospital interface. METHOD: The evaluation examined the model's
      outcomes and participants' experiences. Outcomes were investigated via
      unstructured interviews with key informants, and analysis of relevant
      documentation. Participants' experiences were elicited via structured interviews
      with 11 Divisional members and 14 hospital representatives. RESULTS: Progress
      towards agreements was made in all cases, with a full agreement being reached at
      one hospital. Negotiations are continuing in the remaining hospitals. Additional
      outcomes were achieved during the process, and included resources and structural
      arrangements involving GPs. Participants were satisfied with the model, but
      certain key issues were identified. CONCLUSION: This evaluation suggests that for
      negotiations between GPs and hospitals to be successful, Divisions must be
      involved and be representative, hospitals must see value in formal agreements,
      their structure must be considered and the process must be collaborative. In the
      current policy context, which emphasises primary care, hospitals and GPs are
      increasingly likely to start working more cooperatively. This model has
      significant potential to improve the interface between the two parties, through
      its formal negotiation process, and could easily be adapted to other settings.

PMID- 8857058
TI  - Sports medicine. Overuse injuries. Part 1: bone.
AB  - Musculoskeletal problems have always been a large part of the general
      practitioner's case load. The development of sports medicine as a separate entity
      has helped define and increase understanding of these problems, many of which are
      managed in a general practice environment. This monthly series is designed to
      improve and update knowledge in this area and provide useful pointers for
      management.

PMID- 8857059
TI  - Disorders of male genitalia.

PMID- 8857060
TI  - An itchy serpiginous lesion.

PMID- 8857061
TI  - A simple case of viral lethargy--or is it?

PMID- 8857062
TI  - Recognition of fellowship.

PMID- 8857063
TI  - Management of allergic rhinitis.

PMID- 8857064
TI  - 30 gauge needles not suitable for babies.

PMID- 8857065
TI  - Diabetic diet allows some indulgence.

PMID- 8857066
TI  - Euthanasia debate.

PMID- 8857067
TI  - Euthanasia debate.

PMID- 8857068
TI  - Practical experience and issues in designing and performing population
      pharmacokinetic/pharmacodynamic studies.
AB  - An expert meeting to discuss issues relating to the design of population
      pharmacokinetic/pharmacodynamic (PK/PD) studies was held in Brussels in March
      1995, under the auspices of the European Co-operation in Science and Technology
      (COST), Medicine (B1) programme. The purpose of the meeting was to discuss the
      experts' experience in designing and performing population PK/PD studies. The
      topics discussed were current practice, logistical issues, ensuring the accuracy
      of data, covariate assessment, communication, and protocol design.

PMID- 8857069
TI  - Elderly patients' problems with medication. An in-hospital and follow-up study.
AB  - OBJECTIVES: To examine medication problems during a stay in hospital and after
      discharge and to identify risk factors that contribute to poor compliance with
      medication a prospective observational study was carried out in an university
      affiliated geriatric hospital and a patients' home. PATIENTS: One hundred and
      nineteen patients admitted from home to the geriatric hospital underwent a
      comprehensive geriatric assessment. They were also tested in opening and removing
      tablets from various common medicine containers. Drug prescriptions before,
      during and after the hospital stay were recorded. Medication use at home was
      observed by a member of a hospital-based home intervention team. The patients'
      reports of their drug therapy was compared with those by their family doctors.
      RESULTS: Of all tested patients 10.1% failed to open at least one container. This
      inability was associated with poor vision, impaired cognitive function and low
      manual dexterity. Compliance with prescribed medication was associated with
      cognitive function, ability to handle medication containers, number of prescribed
      drugs and recent changes in drug prescriptions. Of the patients only 39.5% had
      stable drug prescriptions during the 3-month study period. Doctor/patient
      agreement concerning drug therapy was low in all age groups. The agreement rate
      and patients' knowledge of their treatment was correlated with cognitive function
      and the number of prescribed drugs. CONCLUSION: Patients' ability to open and
      remove tablets from common commercial packages/containers should be tested
      routinely during a stay in hospital. Management of medication should be taught
      and supervised within the first few days after discharge from hospital.

PMID- 8857070
TI  - Increased risk of ischaemic heart disease mortality in elderly men using
      anxiolytics-hypnotics and analgesics. Results of the 10-year follow-up of the
      prospective population study "Men born in 1914", Malmo, Sweden.
AB  - OBJECTIVES: An increased risk of all-cause and cardiovascular mortality in users
      of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may
      be an additional factor. Therefore, we examined the association of AHD and
      analgesic use, alone and in combination, with all-cause and ischaemic heart
      disease (IHD) mortality. METHODS: Multivariate 10-year survival analysis in a
      population based cohort of 500 men born in 1914. Relative risks (RR) were
      adjusted by relevant confounders (blood pressure, serum cholesterol, diabetes
      mellitus, smoking habit, high alcohol consumption, history of previous IHD,
      cancer, and other diseases). RESULTS: The RR of both all-cause and IHD mortality
      were significantly increased among those using both AHD and analgesics compared
      to those who took neither of these drugs: RR = 1.8 for all-cause mortality, and
      RR = 2.7 for IHD mortality. CONCLUSION: Although the number of cases was small,
      warranting interpretative caution, the current study suggests that the combined
      use of AHD (mainly benzodiazepines) and analgesics seems to be associated with an
      increase in all-cause and IHD mortality in elderly men.

PMID- 8857071
TI  - Lisinopril reduces postexercise albuminuria more effectively than atenolol in
      primary hypertension.
AB  - Physical exercise causes transient albuminuria. The mechanisms of postexercise
      albuminuria are not fully clarified but stimulation of the reninangiotensin
      system (RAS) probably plays a major role through intrarenal haemodynamic changes
      causing an elevated filtration pressure. In a randomised, double-blind, crossover
      study we compared the effects on urinary albumin excretion (UAE) of lisinopril
      (L) and atenolol (A) therapy, i.e. we aimed to investigate whether inhibition of
      the RAS or inhibition of beta1-adrenoceptor-mediated effects of the sympathetic
      nervous system differed with regard to changes in UAE. Sixteen patients with
      uncomplicated primary hypertension were studied. Four standardised bicycle
      ergometer exercise tests were performed, before and after each active treatment
      period. UAE 30 min postexercise, determined by radioimmunoassay, was
      significantly lowered by both treatments: -278 mu g center dot min-1 (L) and -199
      mu g center dot min-1 (A). The reduction of postexercise UAE achieved by
      treatment with the angiotensin-converting enzyme (ACE) inhibitor (L) was
      significantly greater than that achieved by the beta1-selective adrenoceptor
      blocker treatment. Blood pressure (BP) at rest and during exercise were equally
      reduced by both drugs. In conclusion, this study showed that antihypertensive
      treatment with an ACE inhibitor was more effective in reducing exercise-induced
      albuminuria than a beta1-selective adrenoceptor-blocking agent with a similar
      degree of BP reduction in patients with uncomplicated primary hypertension. This
      suggests that the RAS plays a major role in postexercise albuminuria in
      hypertensive subjects. The clinical significance of this finding, however,
      remains to be clarified.

PMID- 8857072
TI  - Tyramine pressor sensitivity in healthy subjects during combined treatment with
      moclobemide and selegiline.
AB  - OBJECTIVE: The objectives of this double-blind study were to assess the
      tolerability and i.v. tyramine pressor response during combined treatment with
      moclobemide and selegiline. SUBJECTS: Two parallel groups of 12 healthy male and
      female subjects were treated with 200 mg moclobemide or 5 mg selegiline b.d. for
      14 days. On Day 7, selegiline or moclobemide was added to the other treatment. IV
      tyramine pressor tests were conducted at baseline and at steady state during mono
      and combined treatment. RESULTS: Treatment with moclobemide and selegiline alone
      was well tolerated, whereas combined treatment led to a slight increase in
      adverse events. Tyramine pressor sensitivity during moclobemide, selegiline and
      moclobemide + selegiline treatment was enhanced, on average, by 2.4-, 1.3- and
      8.4-times, respectively. CONCLUSION: Although combined treatment with moclobemide
      and selegiline was well tolerated, the supra-additive potentiation of the
      tyramine pressor effects means that dietary restriction of tyramine intake will
      be necessary during such combination therapy.

PMID- 8857073
TI  - Design of a suitable formulation of FK613, a novel antiallergic agent, based on
      its pharmacokinetic and pharmacodynamic properties in healthy subjects.
AB  - The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl
      piperidine derivative, were investigated after oral administrations of 5, 10 and
      20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and
      almost completely absorbed, and >89% was recovered in the urine as the unchanged
      form. The urinary excretion of FK613 was linearly correlated with plasma
      concentration and its low water solubility was the main concern regarding the
      safety. In another experiment using a double-blind crossover design, in which 0
      (placebo), 5 and 20 mg FK613 were administered to determine the plasma
      concentration-effect relationship, suppression of the intradermal histamine
      induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma
      concentration of FK613 in the range of 80-250 ng center dot ml-1 was recommended
      to ensure the suppression of histamine-induced wheal by >50% and not to exceed
      the solubility in urine. To achieve this, a new hydrogel-type formulation of
      FK613 was developed, with the aim both of delaying its absorption, so as to
      suppress the sharp rise in plasma concentration, and of maintaining the effective
      concentration for a longer period of time. This formulation was administered
      after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40
      mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in
      healthy subjects. The area under the plasma concentration curve increased
      linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as
      dose increased, indicating the desirable properties of this formulation. Although
      Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation
      was observed on careful inspection of urine.

PMID- 8857074
TI  - A limited sampling method to estimate methotrexate pharmacokinetics in patients
      with rheumatoid arthritis using a Bayesian approach and the population data
      modeling program P-PHARM.
AB  - This paper describes a methodology to calculate methotrexate (MTX)
      pharmacokinetic parameters after intramuscular administration using two samples
      and the population parameters. Total and free MTX were measured over a 36-h
      period in 56 rheumatoid arthritis patients; 14 patients were studied after a two
      dose scheme at 15-day intervals. The Hill equation was used to relate the free
      MTX to the total MTX changes in plasma concentrations, and a two-compartment open
      model was used to fit the total MTX plasma concentrations. A non-linear mixed
      effect procedure was used to estimate the population parameters and to explore
      the interindividual variability in relation to the following covariables: age,
      weight, height, haemoglobin, erythrocyte sedimentation rate, platelet count,
      creatinine clearance, rheumatoid factor, C-reactive protein, swelling joint
      count, and Ritchie's articular index. Population parameters were evaluated for 40
      patients using a three-step approach. The population average parameters and the
      interindividual variabilities expressed as coefficients of variation (CV%) were:
      CL, 6.94 l center dot h-1 (20.5%); V, 34.8 l (32.2%); k12, 0.0838 h-1 (47.7%);
      k21, 0.0769 h-1 (61.6%); ka, 4.31 h-1 (58%); Emax, 1.12 mu mol center dot l-1
      (19.7%); gamma, 0.932 (12.3%); and EC50, 2.14 mu mol center dot l-1 (27.3%).
      Thirty additional data sets (16 new patients and 14 patients of the previous
      population but treated on a separate occasion) were used to evaluate the
      predictive performance of the population parameters. Twelve blood samples were
      collected from each individual in order to calculate individual parameters using
      standard fitting procedures. These values were compared to the ones estimated
      using a Bayesian approach with population parameters as a priori information
      together with two samples, selected from the individual observations. The results
      show that the bias was not statistically different from zero and the precision of
      these parameters was excellent.

PMID- 8857075
TI  - Rectal pharmacokinetics of budesonide.
AB  - The pharmacokinetics and systemic availability of budesonide after rectal
      administration of two single enema doses (2 mg in 100 ml fluid of almost
      identical composition) were compared in 15 healthy volunteers. In 11 of these
      subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate
      occasion. An intravenous administration (0.5 mg) was given as reference. With
      this design, individual hepatic bypass of the rectally administered budesonide
      dose could be estimated. The pharmacokinetics of the two enema formulations were
      similar, although not bioequivalent. Mean systemic availability was 16% (range
      4.2-43%) and 15% (3.2-50%) after rectal administration and 6.3% (2.4-10%) after
      oral administration. The rectal data revealed a small intra- but a substantial
      inter-subject variability in systemic availability. Cmax was 3.3 nmol center dot
      l-1 (0.95-8.2), 3.0 nmol center dot l-1 (0.64%-8.9) and 1.3 nmol center dot l-1
      (0.61-3.0), respectively, for the three formulations. Absorption was rapid and
      essentially terminated within 3 h after rectal dosing [tmax = 1.3 h for both
      formulations (range 0.5-2.0)], but was slower after oral dosing [tmax = 2.1 h
      (1.0-6.0)]. If a complete absorption after oral and rectal dosing is assumed, the
      fraction of the rectal dose entering the liver at first pass can be calculated to
      be 88% (55-99%). The higher systemic availability and intersubject variability
      after rectal dosing does not seem to be caused by differences in first-pass liver
      metabolism but rather by hepatic bypass of a varying portion of administered
      drug. This portion seems to be typical for an individual and might be explained
      by anatomical differences between subjects.

PMID- 8857076
TI  - Interindividual variability in the rate of salbutamol sulphation in the human
      lung.
AB  - The beta2-adrenergic agonist salbutamol is administered by inhalation to treat
      lung-obstructive disease. Salbutamol is metabolized by conjugation with sulphate,
      and the sulphation of salbutamol was investigated in human lung. Specimens of
      lung were obtained at lobectomy from 11 non-smokers, 39 smokers and 46 ex
      smokers, the latter refraining from smoking at least 6 months before surgery.
      Neither sex nor ageing influenced the activity of sulphotransferase. The rate of
      salbutamol sulphation (pmol center dot min-1 center dot mg-1) was greater in non
      smokers (27.7) than in smokers (21.3), whereas it was similar in smoker and ex
      smokers (22.8). The rate of salbutamol sulphation ranged up to six fold and its
      distribution did not deviate from normality. As the rate of formation of the
      inactive salbutamol sulphate varied in the lung, the availability of salbutamol
      and, in turn, the evoked pharmacological effect should vary in parallel. The
      activities of salbutamol and dopamine sulphotransferase correlated, suggesting
      that catechol sulphotransferase takes part in the sulphation of salbutamol. The
      sulphation of salbutamol is stereoselective in the human lung, the kM estimate
      for (+)- salbutamol (1198 mu M) being greater than those for either (-)
      salbutamol (190 mu M) and racemic salbutamol (142 mu M). These results are
      consistent with the view that (-)-salbutamol is a better substrate than (+)
      salbutamol for sulphotransferase.

PMID- 8857077
TI  - Role of human liver microsomal CYP2C9 in the biotransformation of lornoxicam.
AB  - OBJECTIVE: The nature of the enzyme(s) catalysing the biotransformation of
      lornoxicam to one of its major metabolites, 5'-hydroxy-lornoxicam, has been
      investigated in human liver microsomes. The reaction kinetics were characterised,
      the affinity of lornoxicam for three major human drug metabolising cytochrome P
      450 isozymes (CYP2C9, CYP2D6 and CYP3A4) was determined, and inhibition of the
      reaction by known substrates (diclofenac, ibuprofen, mefenamic acid, phenytoin,
      tolbutamide and warfarin) and the prototype inhibitor (sulphaphenazole) of CYP2C9
      was investigated. RESULTS: Lornoxicam 5'-hydroxylation displayed single enzyme
      Michaelis-Menten kinetics, with a KM of 3.6 mu mol center dot l-1 and a Vmax of
      2.6 nmol center dot h-1 center dot mg-1 microsomal protein. The apparent affinity
      of lornoxicam was high for CYP2C9, but negligible for CYP3A4 and CYP2D6.
      Inhibition of lornoxicam 5'-hydroxylation by CYP2C9 substrates and
      sulphaphenazole competitively and completely inhibited lornoxicam 5'
      hydroxylation (Ki = 0.31 mu mol center dot l-1 as well as lornoxicam clearance
      (Ki = 0.33 mu mol center dot l-1), partial metabolic clearance (fm) = 0.95).
      CONCLUSION: 5'-Hydroxylation appears to be the only cytochrome P-450 catalysed
      metabolic reaction of lornoxicam by human liver microsomes and this major in vivo
      biotransformation pathway is catalysed virtually exclusively by CYP2C9.

PMID- 8857078
TI  - Biotransformation of caffeine by cDNA-expressed human cytochromes P-450.
AB  - OBJECTIVES: The biotransformation of caffeine has been studied in vitro using
      human cytochrome P-450 isoenzymes (CYPs) expressed in human B-lymphoblastoid cell
      lines, namely CYP1A1, 1A2, 2A6, 2B6, 2D6-Val, 2E1 and 3A4, and microsomal epoxide
      hydroxylase (EH). In addition, CYP2D6-Met was also studied, in which a valine in
      the wild type (CYP2D6-Val) has been replaced by a methionine due to a G to A
      mutation in position 112. RESULTS: At caffeine 3 mmol center dot l-1, five CYPs
      (1A1, 1A2, 2D6-Met, 2E1 and 3A4) catalysed the biotransformation of caffeine.
      Among the enzymes studied, CYP1A2, which predominantly catalysed paraxanthine
      formation, had the highest intrinsic clearance (160 l center dot h-1 center dot
      mmol-1 CYP). Together with its high abundance in liver, it should be considered,
      therefore, to be the most important isoenzyme in caffeine metabolism. The
      affinity of caffeine for CYP1A1 was comparable to that of its homologue 1A2.
      CYP2D6-Met, which catalysed caffeine metabolism by demethylation and 8
      hydroxylation, also had a relatively high intrinsic clearance (3.0 l center dot h
      1 mmol-1 CYP), in particular for theophylline and paraxanthine formation, with kM
      values between 9-16 mmol center dot l-1. In contrast, the wild type, CYP2D6-Val,
      had no detectable activity. In comparison, CYP2E1 played a less important role in
      in vitro caffeine metabolism. CYP3A4 predominantly catalysed 8-hydroxylation with
      a kM value of 46 mmol center dot l-1 and an intrinsic clearance of 0.60 l center
      dot h-1 center dot mmol-1 CYP. Due to its high abundance in human liver, the
      latter CYP may contribute significantly to the in vivo formation of TMU.
      CONCLUSION: The findings of this study indicate that i) microsomes from
      transfected human B-lymphoblastoid cell lines give results close to those
      obtained with microsomes isolated from human liver, ii) at least four CYP
      isoforms are involved in caffeine metabolism, iii) at a substrate concentration
      <0.1 mmol center dot l-1, CYP1A2 and 1A1 are the most important isoenzymes, iv)
      at higher concentrations the participation of other isoenzymes, in particular
      CYP3A4, 2E1 and possibly also CYP2D6-Met, are important in caffeine metabolism,
      and v) the nucleotide composition at position 1120 of CYP2D6 determines the
      activity of this isoenzyme in caffeine metabolism.

PMID- 8857079
TI  - Increase in magnesium plasma level after orally administered trimagnesium
      dicitrate.
AB  - Magnesium plasma concentrations were measured in healthy probands before and
      after administration of trimagnesium dicitrate by the oral and intravenous
      routes. There was a notable circadian fluctuation of the plasma concentration
      with a peak in the evening hours. After oral administration of 12 and 24 mmol
      magnesium, a long-lasting, statistically significant increase in plasma magnesium
      concentration measured as the increase in area under the curve (AUC) between 0
      and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous
      administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%,
      respectively. The decline in the plasma magnesium concentration after i.v.
      administration was compatible with a three-compartment model with a terminal half
      time of about 8 h. Although no absolute value of the oral bioavailability of
      trimagnesium dicitrate could be determined from the data, our results may be
      important in helping to elucidate the influence of magnesium preparations on the
      plasma magnesium concentration. By comparing the effects of different
      preparations, it should be possible to estimate the relative oral bioavailability
      and the bioequivalence of these preparations.

PMID- 8857080
TI  - A pharmacokinetic-pharmacodynamic model for a muscle relaxant: atracurium.
AB  - Our goal was to develop a pharmacokinetic-pharmacodynamic model that describes
      the fate of atracurium and its metabolite laudanosine as well as the time course
      of the neuromuscular block. The model was based on the consideration of mass
      balance of atracurium and was constructed by postulating an effect compartment
      linked to the central compartment in the previously described open mammillary
      model for atracurium. The entry and exit rate constants, kCE and kEC, were
      adjusted to satisfy the requirement that the peak amount in the effect
      compartment coincides with the peak submaximal block. We used previously
      published clinical data to arrive at the times to 50% neuromuscular block either
      during the onset of the block following an ED50 dose or during the recovery
      following larger doses of atracurium. Laplace transforms were used to define the
      model, and the solution was obtained by iterative numeric adjustments of the rate
      constants. The model provides an excellent fit of the observed plasma
      concentrations of atracurium and laudanosine and simulates well the development
      and waning of the neuromuscular block. The model projects that the peak amount of
      atracurium in the effect compartment amounts to 14% of the injected dose and is
      reached at 7.6 min after the injection.

PMID- 8857081
TI  - [Hospital system in the year 2000].

PMID- 8857083
TI  - [Hospital reform in Copenhagen. Rationalization, cost saving, quality
      development, research and education].

PMID- 8857082
TI  - [Research in the frontline. Consequences for hospital function and hospital
      structure].

PMID- 8857084
TI  - [Research must be profiled within a new health care structure. Interview by Eva
      Oldinger].

PMID- 8857085
TI  - [What can we do with the smaller hospitals?].

PMID- 8857086
TI  - [The Anders Jahres Prize. Intracellular signal transmission via dioxin
      receptors].
AB  - The intracellular dioxin receptor mediates the biological effects of dioxins and
      related environmental pollutants. The dioxin receptor belongs to a novel subclass
      of DNA binding transcription factors. In addition to the receptor, this very
      class comprises a neurodevelopmental factor in Drosophila [correction of
      Drosphila] melanogaster, and a gene on chromosome 21 that is possibly critical
      for Down syndrome in man. In analogy to the dioxin receptor these factors may
      represent "orphan" receptors with as yet unidentified classes of ligands. The
      mechanism of action of the dioxin receptors is similar to that of members of the
      steroid hormone receptor gene family. Structurally, however, the dioxin receptor
      is distinct from steroid hormone receptors.

PMID- 8857087
TI  - [Crib death and infant mortality in Scandinavia 1988-1993].
AB  - During the years 1970-1989 there was a marked increase in cot death in the Nordic
      countries Denmark, Finland, Norway and Sweden. Since 1990 cot death has decreased
      dramatically, especially in Norway and Denmark. Mortality rates have decreased by
      74 per cent between 1989 and 1993 in Norway and by 69 per cent between 1991 and
      1993 in Denmark. Investigations in Norway during the same period have shown a
      change in the sleeping positions of infants, from prone positions to supine/side
      positions. Infant mortality rates have decreased in all the Nordic countries and
      in 1993 varied from 5.45 per thousand live births in Denmark to 4.40 in Finland.

PMID- 8857088
TI  - [Thrombolysis or angioplasty in acute heart infarct?].
AB  - PTCA (percutaneous transluminal coronary angioplasty) has proved to be safe and
      effective treatment for myocardial infarction which, as compared with
      thrombolytic treatment, yields more complete revascularisation, better coronary
      blood flow, reduced mortality, lower relapse rates, and shorter treatment times.
      There are strong indications that in the near future PTCA will also be accorded a
      prominent place in the treatment of infarction in the Nordic countries. This will
      entail changes in the structure of myocardial infarction care.

PMID- 8857089
TI  - [Detail and suppressed wholeness].

PMID- 8857090
TI  - [What can be expected from a cardiologist in Europe?].

PMID- 8857091
TI  - [Role of MR imaging in the differentiation of benign and nonbenign intracranial
      meningiomas: the utility of contrast-enhanced T1-weighted images].
AB  - The purpose of this study was to develop useful criteria for distinguishing
      nonbenign (atypical and malignant) primary intracranial meningiomas from their
      benign counterparts by using magnetic resonance imaging (MRI). To determine
      useful MRI findings for this purpose, 12 benign and five nonbenign meningiomas
      were retrospectively evaluated according to the following items: 1) tumor signal
      intensity on plain T1-, T2- and proton density-weighted images, 2) degree of
      perifocal edema on T2-weighted images, 3) morphology of the tumor margin on
      contrast-enhanced T1-weighted images, 4) presence of irregular nodule and/or
      mushrooming pattern on contrast-enhanced T1-weighted images, 5) homogeneity of
      the tumor on contrast-enhanced T1-weighted images and 6) presence of marked skull
      destruction. Markedly irregular tumor margin, presence of irregular nodule and/or
      mushrooming pattern and markedly inhomogeneous enhancing pattern were
      significantly more frequent in nonbenign meningiomas. We defined these three MRI
      findings as nonbenign findings, and tried to categorize meningiomas by the number
      of nonbenign findings. It was found that 10 meningiomas with no or one nonbenign
      finding were benign lesions, of four meningiomas with two nonbenign findings two
      were benign lesions and two were nonbenign lesions, and three meningiomas with
      three nonbenign findings were nonbenign lesions. The two benign meningiomas with
      two nonbenign findings were accompanied by increased mitotic activity or brain
      invasion. Contrast-enhanced T1-weighted images were considered very useful in
      distinguishing benign and nonbenign meningiomas.

PMID- 8857092
TI  - [MR imaging of hematopoietic regions in bone marrow of aplastic anemia :
      diagnostic usefulness of opposed phase T1-weighted images].
AB  - The signal intensity of hematopoietic regions in the marrow of aplastic anemia
      were investigated on opposed phase T1-weighted images (op-T1WI) with a 0.5-Tesla
      MR unit. Hematopoietic regions were classified into two groups : 1) low intensity
      hematopoietic areas (LH) isointense to normal marrow and 2) high intensity
      hematopoietic regions (HH) with higher intensity than normal marrow on op-T1WI.
      a) The signal intensity of LH was significantly lower than that of HH on STIR. b)
      LH converted in to HH with improvement of laboratory data after therapy, whereas
      HH decreased with impairment of data. c) In addition, HH were hyperintense to
      cerebrospinal fluid on op-T1WI. These results indicated that the signal intensity
      of hematopoietic regions on op-T1WI reflected the cellularity in these regions
      and that aplastic anemia included hypercellular regions relative to normal
      marrow.

PMID- 8857093
TI  - [Quantification of blood flow using MR imaging with pre-saturation band].
AB  - A velocity profile was obtained by magnetic resonance (MR) imaging with a pre
      saturation band (PSB) and automatically analyzed using a personal computer with
      the data transferred through the picture archiving communication system (PACS). A
      phantom study showed a good correlation of the measured flow rate to the actual
      volumetric flow rate (R?2 = .984; MR rate = 0.11 + 0.90 x actual rate ml/min).
      Images were also obtained in 11 healthy fasting male volunteers during a 16-sec
      breath-hold. The average portal blood flow of these subjects was 16.2 + 5.0
      mil/min/kg body weight. Quantitative MR imaging with PSB is a practical and
      noninvasive technique for measuring volumetric flow rate in the portal venous
      system.

PMID- 8857094
TI  - [A new embolic material: super absorbent polymer (SAP) microsphere and its
      embolic effects].
AB  - SAP-Microsphere (sodium acrylic acid-vinyl alcohol copolymer) has the ability to
      absorb fluids within a few minutes and increase its diameter. Its diameter can
      also be calibrated. The diameters in ionic contrast material and human serum are
      2.1 and 3.5 times larger, respectively, than the original size. It can pass
      through a microcatheter with an ionic contrast material, and swells at the
      occluding point into the desired size. It can be recognized under fluoroscopy due
      to its absorption of contrast material. A total of 10 rabbit kidney embolizations
      were done followed by resection in 1-14 weeks. Recanalization was absent in all
      cases. No adhesion to the perirenal tissue was found. Limited reactive change in
      endothelial cells was found at one week. No changes in the smooth muscle layer
      were found at any time during the study. Limited infiltration of neutrophil cells
      was found in perivascular tissue within a period of one week. SAP-Microspheres
      maintained their spherical shape during a 14-week period. Extensive fibrosis and
      calcification were found after 4 weeks. SAP-Microspheres are promising as an
      embolic agent to obtain satisfactory results of embolization therapy.

PMID- 8857095
TI  - [Serial magnetic resonance imaging of acute disseminated encephalomyelitis,
      including evaluation of the contrast-enhancing effect of lesions by Gd-DTPA].
AB  - Many papers on the MR features of acute disseminated encephalomyelitis (ADEM)
      have been published, but only a few described contrast-enhanced MRI for this
      disease. In this study, we analyzed serial changes in MR features and the
      contrast-enhancing effect on lesions in five patients (5 men, 4-19 years old)
      discharged with the final diagnosis of ADEM. Hyperintense lesions in brain/spinal
      cord were demonstrated on T2-weighted MR images in all cases, but not all lesions
      were enhanced by Gd-DTPA. In the follow-up study many lesions disappeared, but
      some lesions were enlarged and some new lesions were found. These findings
      suggest that, although ADEM is clinically monophasic, some cases may progress
      with the coexistence of reducing, vanishing, and new lesions. Some clinically
      acute lesions were not enhanced. This might be explained by the following reasons
      ; lesions on various phases coexist ; the damage to the blood-brain barrier in
      the lesions is of different degrees even if it is on the same phase ; the
      duration of acute phase activity is short. Additionally, some hyperintense
      lesions remained for a long time on T2-weighted images in spite of the absence of
      clinical manifestation. That hyperintense area might reflect edema caused by
      incomplete repair of the blood-brain barrier. From our evaluation of these five
      cases, MRI is not useful for the diagnosis and follow-up study of ADEM.

PMID- 8857096
TI  - [Standardization of use of 4-F size catheter for selective transcatheter
      angiography and intervention of abdomen].
AB  - To evaluate the safety and efficacy of a new 4 French (F) catheter/sheath system
      with large lumina for selective abdominal arteriography and intervention, the
      usefulness of the 4F sheath (4F group, 88 patients) was compared with that of a
      5.5F sheath and a 7F sheath (5.5F group, 7F group, 156 patients). The compression
      time of the arterial puncture site and the ambulation time in the 4F group were
      significantly shorter than those in the 5.5F and 7F groups. The hemorrhagic
      complication rate in the 4F group (15%) was less than those in the 5.5F group
      (23%) and 7F group (27%). The severity of hemorrhagic complications in the 4F
      group (hematoma 2.3%, woozing 14%, and rhexis 0%) was significantly less than in
      the 5F group (3%, 21%, 0%) and 7F group (11%, 19%, 2.4%). The controlability of
      the 4F catheter as compared with a 5F catheter was estimated in 35 patients by
      questionnaire. The torque transmissibility and the endurability of the kink of
      the 4F catheter were poor in comparison with the 5F catheter. However, with
      respect to the ability to follow over a guidewire, the 4F catheter showed great
      advantage over the 5F catheter. It is concluded that the 4F catheter/sheath
      system is feasible for general use in selective abdominal arteriography and
      interventions.

PMID- 8857097
TI  - [Evaluation of the usefulness of whole body bone mineral measurement using dual
      energy x-ray absorptiometry for the diagnosis of osteoporosis in Japanese women].
AB  - Although dual energy X-ray absorptiometry (DXA) of the anterior-posterior lumbar
      spine (AP L2-3-4 spine) has been established as a standard procedure by which to
      assess bone mineral content (BMC), in some cases it does not reflect the true
      value because of focal sclerosis or other pathological conditions. The purpose of
      this investigation was to determine the most reliable index of BMC for assessing
      osteopenia. Bone mineral densitometry was performed at various sites (whole body,
      AP L2-3-4 spine, lateral L3 spine, femur, and distal radius) in 340 Japanese
      women. Vertebral fracture, a reliable indicator of osteopenia, was disclosed in
      37 subjects. DXA measurements of various sites were obtained, and the bone
      mineral information was evaluated by comparing the procedure's discriminative
      ability between women with and without fractures. In addition to conventional
      whole body BMC (WBBMC) and whole body BMD (WBBMD), the total bone index (TBI),
      which was defined as WBBMC divided by the BMI (body mass index), was also
      evaluated. Of all the bone mineral information, TBI showed the best
      discriminative ability. Whole body bone mineral densitometry was useful.

PMID- 8857098
TI  - [Endobronchial brachytherapy with high dose rate 192Ir afterloading technique
      using a new applicator].
AB  - Recently, high dose rate endobronchial brachytherapy has been carried out for the
      treatment of lung cancer. We devised a new applicator for Ir-192 high dose rate
      brachytherapy that can position the source in the center of the bronchial lumen,
      and tried to set up reference points according to bronchial diameter, for optimal
      dose distribution. Treatment consisted of external beam radiotherapy (40-60 Gy in
      4-6 weeks) and endobronchial brachytherapy (6 Gy x 3 fractions for curative
      intent, 10 Gy x 1 fraction for palliative intent). Reference dose points were 3,
      5, 7 and 10 mm from the center of the source according to bronchial diameter. We
      treated 19 patients with endobronchial brachytherapy and used the new applicator
      in 13 of them. We could place the applicator in all 13 patients, and no
      remarkable side effects were observed during the observation period. Our newly
      designed applicator will help to reduce radiation side effects caused by
      irradiation overdose due to adherence of the source to the bronchial wall. The
      reference point should be set according to bronchial diameter not only for
      curative intent but also palliative intent.

PMID- 8857099
TI  - [Characteristics of radiopharmaceutical delivered from 99mTc-DTPA in the
      technegas generator].
AB  - 99mTc-DTPA aerosol permeates the alveolar membrane by an intercellular pathway.
      Measurement of the clearance rate of 99mTc-DTPA aerosol is useful for assessing
      injury of the lung epithelium. Pertechnegas (P-gas) is also used to assess
      epithelial permeability, but its clearance is too rapid to evaluate lung
      epithelial permeability. The aims of this study were first to generate 99mTc-DTPA
      fine aerosol (D-gas), second to characterize D-gas by radiochromatography and an
      in vivo study in the rat, and third to investigate the clinical significance of D
      gas in comparison with 99mTc-DTPA aerosol and P-gas. We generated D-gas in a
      chamber with an atmosphere of 3% oxygen and 97% argon inside the Technegas
      Generator. The clearance half-time of D-gas was 19.8 +/- 4.0 min in eight normal
      non-smoker subjects, 12.0 +/- 2.8 min in four smoker subjects, and 31 +/- 11.2
      min in three with idiopathic interstitial pneumonia (IIP). In
      radiochromatography, the development of D-gas was the same as that of P-gas and
      different from that of 99mTc-DTPA solution. In the in vivo study using a rat, the
      distribution of intravenously injected D-gas solution was the same as that of
      99mTcO4-, but different from that of 99mTc-DTPA solution. These results suggest
      that 99mTc-DTPA separates to free 99mTcO4- in the chamber of the Technegas
      Generator and that D-gas behaves in the same manner as P-gas. In conclusion, D
      gas has no clinical significance for the assessment of epithelial permeability.

PMID- 8857100
TI  - [Diagnostic value of high N-isopropyl-p-[123I] iodoamphetamine (IMP) uptake in
      brain tumors].
AB  - The diagnostic value of high N-isopropyl-p-[123I] iodoamphetamine (123I-IMP)
      uptake in histologically proven intracranial tumors was evaluated in 54 patients
      with both early (15-35 min after injection) and delayed (4 hours) SPECT before
      treatment. Higher uptake in the tumor compared with normal cerebral cortex was
      observed in early scans in all of the five patients with primary intracranial
      malignant lymphoma, in two of 16 meningiomas, two of seven astrocytomas, one of
      three pituitary adenomas, and one central neurocytoma. Among these 11 cases all
      the malignant lymphomas showed persistent high uptake in delayed scans, whereas
      other tumors showed decreased uptake in delayed scans. This persistent high 123I
      IMP uptake was characteristic of primary intracranial malignant lymphomas and was
      useful in the diagnosis of intracranial malignant lymphoma.

PMID- 8857101
TI  - [Double lumen--coaxial catheter system for combined CT during arterial
      portography and CT hepatic angiography].
AB  - The high sensitivity of CT during arterial portography (CTAP) for hepatic lesions
      is accompanied with a lack of specificity for diagnosis. Combined CTAP and CT
      hepatic angiograpy (CTHA) had been proved to improves lesion detection and
      heightens confidence in interpreting perfusion abnormalities. We describe a new
      double lumen - coaxial catheter system for performing combined CTAP and CTHA
      without the need for repeated transfer of the patient or bilateral arterial
      punctures. This technique was employed in eight patients with liver neoplasms. In
      all eight patients, CTAP and CTA images were obtained successfully. We concluded
      that this method was useful for the evaluation of liver tumors.

PMID- 8857102
TI  - [Ultra-low-dose spiral (helical) CT of the thorax: a filtering technique].
AB  - To reduce the radiation dose from spiral (helical) CT, a custom-made aluminium
      filter was installed in the X-ray tube and a reduction of effective tube current
      was attempted. A pronounced reduction of effective tube current, namely, 6 and 3
      mA, was achieved with 26 and 37 mm thick aluminium filters, respectively.
      Visualization of normal lung structure was accomplished with both 6 and 3 mA
      settings. However, images of 3 mA failed to delineate mediastinal structures
      because of marked beam hardening resulting from the bone structure of the
      thoracic inlet. Six mA was considered the lowest dose setting of spiral (helical)
      CT of the thorax that could be used for lung cancer screening.

PMID- 8857103
TI  - [3D contrast MR angiography of lower extremity : additional imaging with
      subtraction].
AB  - Immediately after pelvic contrast MRA, subtraction MRA with additional
      administration of contrast agent was performed for evaluation of the
      femoropopliteal artery. Mask images were taken with three- dimensional spoiled
      GRASS (24/6.9/40 degrees), followed by contrast images with 7.5 - 10 ml of Gd
      DTPA. The subtracted images provided excellent depiction of the arteries without
      the disruption of overlapping from the venous system or surrounding tissues.
      Seven lesions of arterial occlusion or stenosis were pointed out by subtraction
      MRA in the nine lesions confirmed with IADSA. Subtraction MRA is feasible for
      long segment imaging of the lower extremities with Gd-DTPA.

PMID- 8857104
TI  - [Etiology of sarcoidosis].

PMID- 8857105
TI  - [Clinical significant correlation between to the onset of bronchial asthma in
      children and family history of allergic diseases. Part 1. Comparison of various
      allergic diseases in the family history and onset of bronchial asthma in
      children].
AB  - Two hundred and forty seven asthmatic and 246 non-asthmatic children were
      evaluated in order to find out the relationship between onset of asthma, family
      history of allergic diseases (FH) and environmental factors. The results are as
      it follows. Child with asthmatic symptoms shows high total serum IgE levels
      with/without FH. Asthma occurs significantly often with FH than without FH. There
      is no significant difference in onset of asthma between father and mother. Child
      has more asthma when either father or mother has asthma than allergic rhinitis.
      We concluded that family history of allergic diseases especially asthma is
      asthmogenic and environmental factors work as aggravating but not asthmogenic
      factors. The specific IgE is influenced by condition of the sensitization than
      family history of allergic diseases.

PMID- 8857106
TI  - [Measurement of serum and sputum eosinophil cationic protein concentrations in
      asthma].
AB  - Concentrations of eosinophil cationic protein (ECP) were measured in serum from
      patients with asthma, patients with chronic obstructive pulmonary disease (COPD),
      and healthy subjects. The relationships between serum ECP concentration and
      percent of predicted FEV1 (%FEV1), and between serum and sputum ECP
      concentrations were also examined in patients with asthma. Serum ECP
      concentration in asthma was significantly higher than those in COPD patients and
      healthy subjects. There was a significant inverse correlation between serum ECP
      concentration and %FEV1 when analysis was restricted to data from asthma patients
      less than 60 years old. ECP concentration in serum and in sputum were
      significantly correlated. These results suggest that in asthma patients,
      eosinophils are activated in serum, and that the degree of eosinophil activation
      in the airway can be estimated by measuring serum ECP to some extent. Because it
      does not require bronchial biopsy or bronchoalveolar lavage, measurement of serum
      ECP may be useful as a minimally invasive monitoring of asthma.

PMID- 8857107
TI  - [Inhibitory effect of low molecular weight heparin on the bronchoconstriction in
      ovalbumin-sensitized guinea pigs after antigen exposure].
AB  - To elucidate the effect of low molecular weight heparin (LMWH) on the
      bronchoconstriction, we examined the serial changes of the resistance of
      respiratory system (Rrs) in ovalbumin (OA)-sensitized guinea pigs after antigen
      exposure. After sensitization of guinea pigs with repeated OA inhalation, Rrs was
      measured at immediate asthmatic response (IAR) and late asthmatic response (LAR)
      with or without LMWH inhalation. Alteration in the number of inflammatory cells
      of the lung by LMWH inhalation was examined in the broncholaveolar lavage fluid
      (BALF) and in the histological sections of airway walls. Peak Rrs at 1 min up to
      9 min, except 8 min, after antigen exposure significantly decreased by the
      pretreatment with LMWH inhalation as compared with saline inhalation. Peak Rrs at
      LAR (after 4 hours up to 24 hours, except 6 hours) also showed a significant
      decrease in the pretreatment with LMWH inhalation. Pretreatment of LMWH exhibited
      a decrease of eosinophil percentage in BALF (5.5 +/- 1.2% from 8.2 +/- 0.4% in
      saline inhalation) and a decrease of infiltrated eosinophil count in airway walls
      (71.0 +/- 7.3 from 155 +/- 15.8 in saline inhalation). These data show LMWH might
      play an important role as an inhibitory factor to bronchial asthma.

PMID- 8857108
TI  - IgE-mediated allergy to spider mite, Panonychus citri in occupationally exposed
      individuals.
AB  - This paper is the first report on allergy caused by a spider mite, Panonychus
      citri. Some of fruitgrowers cultivating Citrus junos were manifested immediate
      allergic symptoms by farming, especially by harvest. By examining C. junos trees,
      we found the trees cultivated by the fruitgrowers were infested with P. citri.
      Twelve subjects complaining of immediate allergic symptoms were examined by
      intradermal test and RAST using allergen extracts prepared from P. citri and
      Dermatophagoides spp. In intradermal test, ten out of twelve showed a positive
      response to P. citri and twelve positive to D. farinae. Positive RAST to P. citri
      were obtained in seven of twelve. Six of them also had positive RAST to D.
      farinae and D. pteronyssinus. In ELISA inhibition using a serum from Case 4, the
      inhibition with P. citri extract reached to 92% at the highest concentration used
      but at the same concentration D. farinae and D. pteronyssinus extracts did not
      inhibit the binding of specific IgE antibodies to allergen of P. citri. In Case
      7, the extracts of P. citri, D. farinae and D. pteronyssinus inhibited at the
      same concentration 94%, 81%, and 87%, respectively. These results lead to the
      following conclusions: Seven subjects positive to P. citri in intradermal test
      and RAST are sensitized to P. citri. P. citri has a specific allergenic
      determinant in addition to a common determinant with Dermatophagoides spp.

PMID- 8857109
TI  - [A case of food-dependent exercise-induced anaphylaxis induced by shrimp].
AB  - The clinical study and in vitro study used with leukocytes were made of a case of
      food-dependent exercise-induced anaphylaxis induced by shrimp. A 26-year-old man
      experienced anaphylactic reaction of nasal obstruction, face edema and dyspnea
      while running 90 minutes after eating shrimp. He experienced similar episodes two
      years ago in his past history. IgE-RAST was positive for shrimp. Anaphylactic
      reaction and elevation of plasma histamine levels were verified by exercise
      challenge test after eating 100 g shrimp. At the same time, we verified the
      dedine of plasma cAMP levels after eating shrimp. In leukocyte stimulating test
      used with shrimp antigen, histamine level elevations, which were lower compared
      with calcium ionophore A23187 (Ca I 10(-6) M) stimulation, were recognized in
      dose dependent manner in this patient. But in normal subject, histamine level
      elevations were not recognized. We diagnosed him food-dependent exercise-induced
      anaphylaxis. It was suggested that there was relation between histamine release
      and decline of cAMP levels of plasma after eating shrimp in this case.

PMID- 8857110
TI  - [Olive pollinosis in Japan].
AB  - Olive (Olea europaes) is the most important allergic tree in the Mediterranean
      area. That is widely distributed at Syodoshima in Japan. I observed olive
      pollination period and studied the patients with pollinosis. The patients were
      examined by skin test, measuring of specific IgE antibody and nasal provocation
      test with olive pollen extract. Allergic responses to olive pollen were found to
      be present in 16.3% of pollinosis patients. And cross-reactivity between olive
      and grass pollen (Dactylis glomerata) was suggested. Other literature reported
      the cross reactivity between the pollens of the Oleaceae family, containing
      olive, and grass family. From our study we suppose that Oleaceae pollens cause
      allergic reaction of Gramineae pollinosis patients in Japan.

PMID- 8857111
TI  - [The detection of factors that may promote the hepatocyte proliferation in the
      serum of a patient with crow-fukase syndrome].
AB  - We reported a case of Crow-Fukase syndrome and examined the mechanism of
      hepatomegaly in Crow-Fukase syndrome. A 67-year-old woman was presented with
      polyneruopathy, hepatosplenomegaly, pericardial effusion and M proteinemia. On
      examination, all laboratory data and clinical symptoms were compatible with Crow
      Fukase syndrome. The patient was treated with prednisolone and immunoadsorption
      plasmaphresis therapy. All the clinical manifestations including hepatomegaly
      gradually improved. In order to examine whether some factors that promote the
      prolifelation of hepatocyte may exist in the patient's serum, we cultured mouse
      hepatocyte in the presence of patient's or control serum together. Though the
      number of hepatocytes decreased after 2 days culture, the number of hepatocytes
      cultured with patient's serum in active disease stage remained significantly
      greater than of hepatocytes cultured with either control serum or patient's serum
      in healing stage. There were no abnormal pathological findings in biopsied liver.
      Liver suggesting that hepatomegaly was the results of normal hepatocytes
      proliferation. Taken together, these findings suggest there were some factors
      that may promote the proliferation of hepatocytes or may have protective effect
      of hepatocyte in patient's serum. Though the level of human hepatocyte growth
      factor (h-HGF) in patient's serum in active disease stage was slightly increased,
      hepatomegaly cannot be attributable solely to h-HGF. Organomegaly is one of the
      important symptoms of the Crow-Fukase syndrome, however, in so far as we are
      aware its mechanism is not examined. In this report it is suggested that several
      unknown factors other than h-HGF may contribute the hepatomegaly of the Crow
      Fukase syndrome.

PMID- 8857112
TI  - [Eosinophil colony stimulating factor (Eo-CSF) activity and soluble interleukin-2
      receptor (sIL-2R) in patients with reactive eosinophilia].
AB  - To explore the pathophysiology of patients with reactive eosinophilia from
      unknown cause, we measured the eosinophil colony stimulating factor (Eo-CSF)
      activity in the interleukin-2 (IL-2) stimulated lymphocyte conditioned medium
      (CM) prepared from 22 patients with reactive eosinophilia. Eo-CSF activity, the
      levels of interleukin-5 (IL-5) and granulocyte-macrophage colony stimulating
      factor (GM-CSF) were increased in the CM from patients with high IgE levels.
      Hydrocortisone decreased the level of Elo-CSF in the CM. Elevated serum levels of
      soluble IL-2 receptor (sIL-2R) were presented in 13 out of 15 patients with
      eosinophilia. The sIL-2R levels in patients with marked eosinophilia (>3000/mu l)
      were higher than those in patients with mild eosinophilia (< or = 3000/mu l).
      High sIL-2R levels were noted in T cell CM from 3 out of 15 patients and in
      eosinophil CM from 1 out of 4 patients. These data suggested that lymphocyte from
      eosinophilic patients with elevated IgE produce Eo-CSF, IL-5 and GM-CSF by IL-2
      stimulation. Eo-CSF production is inhibited by hydrocortisone. SIL-2R is released
      from lymphocyte and in some case may be released from eosinophils.

PMID- 8857113
TI  - Suppression of cytokine production of human memory T cells by roxithromycin.
AB  - Recent reports have suggested that erythromycin (EM) might have immunomodulatory
      activities. Roxithromycin (Rox) is a new macrolide, which has more favorable
      pharmacokinetic properties than EM. The current studies therefore examined the
      effects of Rox on the in vitro function of human T cells. Interferon-gamma (IFN
      gamma) production was induced from highly purified T cells and CD45RA (-) T cell
      subsets from normal individuals by stimulation with immobilized anti-CD3. Rox at
      its pharmacologically attainable concentrations suppressed the IFN-gamma
      production of CD45RA (-) T cells stimulated with immobilized anti-CD3, but not
      that of unfractionated T cells. EM also preferentially suppressed the IFN-gamma
      production of CD45RA (-) T cells, but less effectively than Rox. Rox also
      preferentially suppressed the IL-2 production of immobilized anti-CD3 stimulated
      CD45RA (-) T cells. These results suggest that Rox may preferentially suppress
      the IFN-gamma production of memory T cells, but not that of naive T cells.
      Moreover, the data call for considering Rox as a possible immunomodulator for the
      treatment of various autoimmune disorders in which the abnormal function of
      CD45RA (-) T cells is involved, especially Behcet's disease.

PMID- 8857114
TI  - Intracorporeal gas exchange: current status and future development.

PMID- 8857115
TI  - Non-invasive mechanical ventilation in severe chronic obstructive lung disease
      and acute respiratory failure: short- and long-term prognosis.
AB  - OBJECTIVE: To evaluate the short- and long-term prognosis of patients with
      chronic obstructive lung disease (COLD) who had noninvasive mechanical
      ventilation (NMV) for acute respiratory failure (ARF). DESIGN: Retrospective
      study. SETTING: Two respiratory intermediate intensive care units. PATIENTS: Two
      groups of patients suffering from COLD and an ARF episode requiring mechanical
      ventilation. Group 1 (30 patients) was given NMV using face masks (aged 64 +/- 9
      years; pH = 7.28 +/- 0.05; PaCO2 = 83 +/- 18 mmHg; PaO2/FIO2 = 141 +/- 61). Group
      2 (27 patients) was composed of control patients (aged = 65 +/- 8 years; pH =
      7.26 +/- 0.05; PaCO2 = 75 +/- 17 mmHg; PaO2/FIO2 = 167 +/- 41) given MV using
      endotracheal intubation (EI) when clinical and functional conditions had further
      deteriorated because the medical therapy failed and NMV was not available at the
      time. Causes of ARF were in group 1 and 2 respectively: pneumonia in 8 (27%) and
      11 (41%), acute exacerbation of COLD in 19 (63%) and 14 (52%) and pulmonary
      embolism in 3 (10%) and 2 (7%) patients. MEASUREMENTS AND RESULTS: Success rate,
      mortality during stay in ICU (at 3 months and at 1 year), and the need for
      rehospitalization during the year following ARF were measured in this study.
      Group 1 showed a success rate of 74%, only 8/30 patients needing EI and
      conventional MV. In group 2, the weaning success was 74% (20/27 patients). The
      mortality for group 1 was 20% in IICU, 23% at 3 months and 30% at 1 year; and 26%
      for group 2 in ICU, 48% at 3 months and 63% at 1 year. Within each group 1-year
      mortality was greater (p < 0.01) in patients with pneumonia. The number of new
      ICU admissions during the follow-up at 1 year was 0.12 versus 0.30 in groups 1
      and 2 respectively (p < 0.05). CONCLUSION: For patients suffering from COLD who
      have undergone ARF, avoiding EI by early treatment with NMV is associated with
      better survival in comparison to patients bound to invasive MV. Pneumonia as a
      cause of ARF may worsen the prognosis in both groups of patients.

PMID- 8857116
TI  - Pulmonary oedema, pneumonia and mortality in submersion victims; a retrospective
      study in 125 patients.
AB  - OBJECTIVE: The identification of risk factors contributing to the development of
      pulmonary oedema, pneumonia and late mortality in submersion victims. DESIGN: A
      retrospective study of 125 submersion victims. SETTING: The medical intensive
      care unit in a university hospital. METHODS: Baseline examination on admission
      consisted of history, physical examination, arterial blood gas analysis and a
      chest radiograph. Patients were then classified into four groups: class I,
      baseline examination negative; class II, baseline examination positive, but
      mechanical ventilation not needed on admission; class III, mechanical ventilation
      required on admission; class IV, patients suffering from cardiopulmonary arrest.
      All patients who were not successfully resuscitated or who had expired within 24
      h after admission were excluded for determination of the risk of pulmonary oedema
      and pneumonia. RESULTS: Class I patients did not develop pulmonary complications;
      neither pulmonary oedema nor pneumonia occurred in this group. In the remaining
      classes the incidence of pulmonary oedema was 72% and that of pneumonia, 14.7%.
      Stepwise logistic regression showed that pulmonary oedema was related to the type
      of water (seawater, ditch water, swimming pool) victims were submerged in and to
      the neurological state both at the time of rescue and on admission. The
      development of pneumonia was related to the use of mechanical ventilation (the
      risk was 52%). Pneumonia was not related to neurological state at the time of
      rescue or on admission, to body temperature on admission, to the prophylactic
      administration of antibiotics or to the use of corticosteroids. Mortality was
      high in class IV patients, but low in all other patients. Early mortality was
      18.4% while late mortality was 5.6%. CONCLUSIONS: There is no need to hospitalise
      submersion victims when there are no signs or symptoms of aspiration upon arrival
      in the emergency room. All other patients should be admitted to an intensive care
      unit. The risk of pneumonia is high when mechanical ventilation is necessary.
      Mortality is high in patients with circulatory arrest on admission, but low in
      all other patients.

PMID- 8857117
TI  - Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles.
AB  - BACKGROUND: Hydroxocobalamin has been shown to be a rapid and powerful antidote
      in acute cyanide poisoning and to prevent cyanide poisoning during sodium
      nitroprusside administration. This cobalt-containing compound has been shown to
      be devoid of significant immediate side effects during acute administration.
      However, its potential delayed toxicity related to cobalt accumulation in tissue
      remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as
      compared with that of cobalt salts on rat cardiac and diaphragmatic muscles.
      METHODS: For a 21-day period, rats were treated intraperitoneally with either
      hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg
      kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride
      groups received equimolar doses of cobalt. We studied: (1) the mechanical
      properties of isolated left ventricular papillary muscles and diaphragmatic
      strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3)
      the myocardial histological aspect. RESULTS: During the study period, no
      significant increase in body weight was noted in the cobalt-treated group (-4 +/-
      1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and
      the saline-treated group (22 +/- 2%). Compared with controls, the mechanical
      properties of cardiac and diaphragmatic muscles were unchanged after either
      hydroxocobalamin or cobalt salt treatments, and myocardial histological
      characteristics were similar in all groups. Conversely, large amounts of cobalt
      deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/
      16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the
      myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P
      < 0.001). After hydroxocobalamin administration, cobalt concentrations were
      significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs
      cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs
      cobalt-treated group). CONCLUSION: These results indicate that repeated
      administration of hydroxocobalamin was devoid of significant diaphragmatic and
      cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide
      poisoning.

PMID- 8857118
TI  - Calcium free hemodialysis: experience in the treatment of 33 patients with severe
      hypercalcemia.
AB  - OBJECTIVE: To assess the efficacy, adverse effects and relevance of calcium-free
      hemodialysis (CFHD) in the treatment of major hypercalcemia. DESIGN:
      Retrospective chart review. SETTING: Medical ICU. PATIENTS: All patients admitted
      over a 9-year period for hypercalcemia requiring urgent treatment and who
      underwent hemodialysis. INTERVENTIONS: CFHD with an acetate dialysate. MAIN
      RESULTS: Thirty-three patients with severe hypercalcemia from various etiologies
      received CFHD. Marked and rapid decrease of serum total calcium was obtained
      during all sessions (mean decrease: 1.71 +/- 0.54 mmol/l). Calcium rebound within
      24 h after CFHD was observed in all evaluable cases (1 +/- 0.45 mmol/l; mean
      delay 13.7 +/- 5.8 h). Adverse cardiovascular effects occurred in 17 of 48
      sessions (35%) and in 13 of 30 evaluable patients (43%). CONCLUSIONS: Adverse
      effects are frequent during CFHD. After correction of hypovolemia, its use should
      be restricted to patients with severe clinical symptoms or advanced renal
      impairment.

PMID- 8857119
TI  - Circulating adhesion molecules in the critically ill: a comparison between trauma
      and sepsis patients.
AB  - OBJECTIVE: The time course of circulating adhesion molecules was monitored in
      traumatized and sepsis patients. DESIGN: Prospective, descriptive. SETTING: A
      surgical intensive care unit of a university hospital. PATIENTS: A total of 30
      consecutive critically ill patients suffering either from trauma (n = 15) or
      postoperative sepsis (n = 15). INTERVENTIONS: All patients were on continuous
      analgo-sedation and mechanical ventilation. MEASUREMENTS AND RESULTS: From
      arterial blood samples, plasma levels of soluble adhesion molecules [endothelial
      leukocyte adhesion molecules (sELAM-1), intercellular adhesion molecule-1 (sICAM
      1)], and vascular cell adhesion molecule-1 (sVCAM-1) were measured on the day of
      admission (trauma patients) or on the day of diagnosis of sepsis (= baseline
      values), and during the following 5 days. In the trauma group, sELAM-1 (57.9 +/-
      11.0 ng/ml) and sVCAM-1 (698 +/- 93 ng/ml) were within normal ranges at baseline,
      whereas they were markedly elevated in the sepsis group (sELAM-1: 340 +/- 95
      ng/ml; sVCAM-1; 1,042 +/- 449 ng/ml). In the sepsis patients, sELAM-1
      significantly decreased and sVCAM-1 increased, but remained almost unchanged in
      the trauma patients. Non-survivors showed markedly elevated plasma levels of
      sELAM-1 and sVCAM-1. sICAM-1 was elevated in both groups at baseline and was
      higher in the sepsis group (1,266 +/- 261 ng/ml) than in the trauma group. In the
      septic patients, sICAM-1 increased further (2,022 +/- 609 ng/ml) and remained
      unchanged in the trauma group. All non-survivors showed sICAM-1 plasma levels of
      > 800 ng/ml. CONCLUSIONS: Endothelial damage may result in multiple-organ
      dysfunction syndrome. Adhesion molecules are considered to be a cornerstone in
      this process. Trauma patients showed lower plasma levels of circulating adhesion
      molecules than did sepsis patients indicating more pronounced (inflammatory
      related) endothelial activation or damage in sepsis. Therapeutic modulation of
      circulating adhesion molecules may be of benefit to the patients outcome and
      therefore warrants further study.

PMID- 8857120
TI  - Intratracheal administration of fentanyl: pharmacokinetics and local tissue
      effects.
AB  - OBJECTIVE: To study the pharmacokinetics and local tissue effects resulting from
      the intratracheal administration of preservative-free fentanyl. DESIGN:
      Prospective, randomized, blinded and controlled animal study. SETTING: University
      research laboratory. SUBJECTS: Eighteen adult male New Zealand rabbits.
      INTERVENTIONS: Preservative-free fentanyl citrate or normal saline was
      administered by the intratracheal (i.t.) and intravenous (i.v.) routes to
      randomized groups of rabbits. The animals were killed at 24, 48 and 72 h
      following administration. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of
      fentanyl were measured before administration and at 2, 5, 10, 30, 60 and 120 min
      following administration by a specific radioimmunoassay. A detailed histological
      examination of the lung and tracheal tissue was performed to identify local side
      effects. There were no significant differences in the plasma fentanyl
      concentrations resulting from the i.v. or i.t. route of administration. In both
      groups, the concentrations of fentanyl were within the therapeutic range (i.t.
      2.37 ng/ml, i.v. 2.53 ng/ml) by 2 min after injection and reached a maximum
      concentration within 5 min. The bioavailability of i.t. fentanyl was 71%.
      Microscopic examination of the respiratory system did not show significant
      differences between the two random groups overall. However, in the sub-group of
      animals killed at 24 h, more animals in the i.t. group showed signs of
      inflammation in the lung parenchyma. CONCLUSIONS: There is rapid absorption of
      fentanyl following i.t. administration. Pharmacokinetic parameters for fentanyl
      were not significantly altered by the route of administration. Although there
      were no signs that i.t. administration of preservative-free fentanyl produces
      lung injury, a transient and mild inflammatory response was detected at 24 h
      after administration.

PMID- 8857121
TI  - Fatigue of the respiratory muscles.

PMID- 8857122
TI  - International comparisons of intensive care: meeting the challenges of different
      worlds of intensive care.

PMID- 8857124
TI  - Guidelines for a training programme in intensive care medicine. European Society
      of Intensive Care Medicine, European Society of Pediatric Intensive Care.

PMID- 8857123
TI  - The role of nitric oxide in sepsis and ARDS: synopsis of a roundtable conference
      held in Brussels on 18-20 March 1995.

PMID- 8857125
TI  - Reversible hepatic cytolysis during almitrine bismesylate treatment for
      posttraumatic ARDS.

PMID- 8857126
TI  - Nocturnal hypoxemia and oxygen desaturation events in neutropenic patients with
      sepsis or pneumonia.

PMID- 8857127
TI  - Prognosis of stroke patients undergoing mechanical ventilation.

PMID- 8857128
TI  - Long-term intravenous cimetidine treatment does not alter cortisol response in
      hemodynamically stable intensive care unit patients.

PMID- 8857129
TI  - Enhancement of hypoxemia by right-to-left atrial shunting in severe asthma.

PMID- 8857130
TI  - Reference accuracy in Intensive Care Medicine.

PMID- 8857131
TI  - Endoscopic snare excision of "giant" colorectal polyps.
AB  - BACKGROUND: Endoscopic treatment of giant colorectal polyps remains controversial
      because of concerns regarding coexistent malignancy, incomplete resection, and
      safety. METHODS: We reviewed the clinical course after removal of 176 benign
      appearing large (>3 cm) colorectal polyps, which were removed by endoscopic snare
      resection in 170 patients. These were termed "giant" polyps. Sessile polyps (n =
      129) were removed piecemeal and pedunculated polyps (n = 47) transected at the
      stalk. RESULTS: Bleeding was the only complication in 24% of polypectomy
      procedures (procedural in 58, immediate in 3, delayed in 6 patients). Except for
      one conservatively treated delayed bleed, all bleeds were treated endoscopically.
      Histology of resected polyps showed coexistent malignancy in 12%. Eight patients
      had malignant polyps that met "unfavorable" criteria and underwent surgery.
      Following complete endoscopic resection, 16 patients were lost to follow-up and
      124 patients had follow-up of at least 6 months (117 benign and 7 "favorable"
      malignant polyps). Nineteen patients with benign polyps developed recurrences (18
      benign, 1 malignant); one patient with a favorable malignant polyp had a
      malignant recurrence and underwent surgery. CONCLUSION: Endoscopic resection of
      benign-appearing giant colorectal polyps is feasible and safe. Complete excision
      is possible in patients with benign and favorable malignant polyps, but
      recurrence rates are high. Close surveillance to detect and treat recurrence is
      required.

PMID- 8857132
TI  - Injection-incision--assisted snare resection of large sessile colorectal polyps.
AB  - BACKGROUND: It can be difficult, even for experienced endoscopists, to completely
      remove large sessile colorectal polyps. We attempted to remove large sessile
      colorectal polyps without complication and residual tumors. METHOD: Our new
      technique is characterized by submucosal pre-injection with a large volume of
      saline solution and then circumferential incision outside the lesion before
      resection using a special needle-tipped snare. The mean size of 33 polyps
      (including 9 elevated sessile, 20 flat nodular [villous], and 4 flat sessile
      polyps), was 4.0 cm (range, 3.0-8.5 cm). RESULTS: Twenty-five (76%) were resected
      piecemeal and the remainder as a single specimen. Mild to moderate bleeding
      occurred in 3 (9.1%), but there was no clinically significant bleeding or
      perforation. No residual or recurrent tumors were recognized. Invasive carcinoma
      was revealed most frequently (44%) in elevated sessile polyps; none occurred in
      flat nodular polyps. CONCLUSION: Our removal technique appears to be safe and
      effective. Flat nodular polyps of any size are a particularly good indication for
      removal by this technique.

PMID- 8857133
TI  - Prior radiation and chemotherapy increase the risk of life-threatening
      complications after insertion of metallic stents for esophagogastric malignancy.
AB  - BACKGROUND: Self-expanding metallic stents (SEMS) are effective in relieving the
      symptoms of obstructing esophagogastric malignancy. While complications with SEMS
      have been described, factors influencing such occurrence have not been defined.
      METHODS: Self-expanding Gianturco-Rosch Z-stents were placed successfully in 59
      patients with obstructing esophagogastric malignancies. RESULTS: Early procedure
      related complications occurred in 6 patients (10%) and were usually minor. Twenty
      three late complications occurred in 22 patients (37.5%). Life-threatening
      complications occurred in 9 patients (15%), including gastrointestinal bleeding
      (7), perforation (1), and tracheoesophageal fistula (1) and contributed to all
      five deaths. Eight of 22 patients with prior radiation and/or chemotherapy
      (36.4%) had life-threatening complications compared to 1 of 37 (2.5%) without
      prior therapy (p = 0.001). Stent-related mortality occurred in 5 of 22 (23%)
      patients with prior therapy compared to none of the 37 without prior therapy (p =
      0.005). Multivariate analysis confirmed the association between prior radiation
      and/or chemotherapy and life-threatening complications (p = 0.012; odds ratio,
      32.63) and also an association with female gender (p = 0.032; odds ratio, 13.9).
      There was no association with tumor location or length, histologic type, age,
      prestent dysphagia grade, or previous surgical resection. CONCLUSION: Patients
      with prior radiation and/or chemotherapy have an increased risk of severe
      complications following placement of SEMS.

PMID- 8857134
TI  - Expandable versus conventional esophageal prostheses: easier insertion may not
      preclude subsequent stent-related problems.
AB  - BACKGROUND: Although expandable esophageal endoprostheses may be easier to insert
      and are associated with fewer procedure-related perforations, data comparing
      clinical results with these stents to those obtained with conventional prostheses
      are sparse. METHODS: We reviewed the records of all patients undergoing
      esophageal stent placement at our institution between October 1983 and July 1995
      to define relative risks, clinical results, and need for reintervention prior to
      death, contrasting conventional to a variety of expandable esophageal
      endoprostheses. RESULTS: Over the period of review, 47 patients had conventional
      prostheses (CP) and 38 had expandable prostheses (EP) placed. Fifteen of 44
      patients with CP and 14 of 38 with EP for malignancy also had esophago-airway
      fistulas. Insertion complications, prestent and poststent dysphagia scores, and
      complete fistula occlusion rates were comparable. Subacute complications were
      higher in the patients receiving EP (80%) than in those receiving CP (60%),
      possibly related to the prospective accumulation of data in patients receiving
      EP. Survival data were virtually identical and approximated 3 months for either
      group. CONCLUSIONS: Although both CP and EP improve dysphagia and occlude
      tracheoesophageal fistulae, patients ill enough to require a prosthesis do poorly
      regardless of prosthesis design. Moreover, although EP may be easier to insert
      than CP, stent- and patient-related problems persist and may require additional
      intervention.

PMID- 8857135
TI  - Premedication with intravenous antispasmodic speeds colonoscope insertion.
AB  - BACKGROUND: Use of antispasmodic medication prior to colonoscopy is controversial
      but may improve visualization of colonic mucosa and ease colonoscope insertion.
      METHOD: The effects on the performance of colonoscopy by premedication with the
      antispasmodic hyoscine n-butyl bromide were studied in a prospective, double
      blind, placebo-controlled trial. Fifty-six consecutive patients were randomly
      assigned to receive intravenous hyoscine 20 mg (n = 29) or placebo (n = 27) in
      conjunction with our standard initial medications (meperidine 0.7 mg/kg and
      midazolam 0.03 mg/kg). Insertion and withdrawal of the colonoscope were timed,
      and 100 mm visual analogue scales were used to assess procedure difficulty,
      colonic motility, and the degree of discomfort experienced by the patients.
      RESULTS: In those patients receiving hyoscine, intubation time was quicker
      (median hyoscine, 13 minutes; median placebo, 17.5 minutes, p = 0.045) and
      colonic spasm less (median hyoscine, 19 mm; median placebo, 53.5 mm, p = 0.01).
      The procedure was considered significantly less difficult in the hyoscine group
      (median, 23.5 mm) compared to the placebo group (median, 50), p <0.05. No
      significant differences in withdrawal time or patient pain scores were found.
      CONCLUSIONS: Premedication with intravenous hyoscine n-butyl bromide reduces
      colonic spasm and in this study made colonoscope insertion significantly quicker
      and easier.

PMID- 8857136
TI  - Selective use of preoperative endoscopic retrograde cholangiopancreatography in
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The management of possible common bile duct (CBD) stones in patients
      scheduled for laparoscopic cholecystectomy remains controversial. METHODS:
      Prospective evaluation of 609 patients who underwent laparoscopic cholecystectomy
      was carried out in relation to the use of selective preoperative ERCP for
      detection of common duct stones. Preoperative ERCP was performed if there is or
      has been (1) cholangitis, biliary pancreatitis, or jaundice; (2) abnormal serum
      liver tests or (3) ultrasonogram showing a dilated CBD or ductal stones. RESULTS:
      A total of 139 patients underwent preoperative ERCP, and cannulation of CBD was
      successful in 133 patients (96%). CBD stones were found in 60 patients (45%) and
      extracted after sphincterotomy. High prevalence of CBD stones was noted in
      patients with acute cholangitis and CBD stones on ultrasonogram. There were six
      endoscopic sphincterotomy-related complications (complication rate, 4.5%):
      bleeding (2), pancreatitis (3), retroduodenal perforation (1). No patient
      required surgery as the result of a complication. The prediction of the
      occurrence of ductal stones was further analyzed using stepwise logistic
      regression. Acute cholangitis and CBD stones on ultrasonogram were shown to be
      independent significant risk factors with odds ratios of 8.9 and 13.5,
      respectively. CONCLUSIONS: With selective preoperative ERCP, suspected CBD stones
      can be identified and removed prior to laparoscopic cholecystectomy.

PMID- 8857137
TI  - A randomized blinded comparison of omeprazole and ranitidine in the treatment of
      chronic esophageal stricture secondary to acid peptic esophagitis.
AB  - BACKGROUND: Esophageal strictures due to gastroesophageal reflux disease are
      often resistant to medical therapy and require repeated dilation procedures. Our
      aim was to compare the efficacy of therapy with omeprazole (20 mg/day) to
      ranitidine (150 mg twice daily) in the treatment of chronic esophageal
      strictures. METHODS: Thirty-three patients with chronic esophageal stricture
      disease (mean length of prior treatment, 50.9 months) were entered into a
      randomized blinded trial. The majority (88%) of the patients had received
      multiple prior esophageal dilations (mean, 7.9 per patient). Endoscopy and barium
      esophagograms were performed initially and at the end of 10 months. Symptoms were
      considered every 2 months and dilations performed as needed. The patient groups
      were equivalent. RESULTS: One patient in each group was subsequently lost to
      follow-up. No significant differences were seen in symptom improvement or need of
      dilation. At the final endoscopy, 8 of 17 (47%) patients receiving ranitidine had
      residual erosions or ulceration, compared with 1 of 14 (7%) patients receiving
      omeprazole (p >0.2). All patients receiving ranitidine had persistent strictures,
      whereas 8 of 14 (57.1%) patients receiving omeprazole had radiographic and
      endoscopic resolution of their strictures (p <0.004). CONCLUSION: These data
      further emphasize the need for vigorously treating esophagitis in patients with
      acid peptic strictures.

PMID- 8857138
TI  - Detection of Helicobacter pylori by rapid urease tests: is biopsy size a critical
      variable?
AB  - BACKGROUND: The variables responsible for false-positive and false-negative rapid
      urease tests are largely unexplored. OBJECTIVES: We compared the results of rapid
      urease testing with jumbo cup forceps (3.3 mm diameter) and tiny cup forceps (1.8
      mm diameter) with two rapid urease tests. METHODS: Antral biopsies were obtained.
      The order of forceps and rapid urease tests was randomized. Biopsies were also
      taken for Genta staining. RESULTS: One hundred and two patients were studied; 59
      had Helicobacter pylori infection. There were 22 false-negative tests (8 CLOtest,
      16 hpfast) and 5 false-positive tests (3 CLOtest, 2 hpfast). All 5 false-positive
      tests were among those positive only in the second 12 hours. There was no
      difference in results with the jumbo and tiny cup forceps. Five percent to nine
      percent (average, 6.6%; 95% confidence interval, 4.4% to 9.6%) of tests with any
      of the combinations gave an erroneous categorization of H. pylori status. There
      were no clinical or statistical differences in H. pylori categorizations by
      CLOtest or hpfast. CONCLUSION: The diagnostic yield for detecting H. pylori
      infection by rapid urease tests is not adversely affected by small biopsy size,
      possibly because tiny biopsies obtain superficial tissue where H. pylori reside.

PMID- 8857139
TI  - Laryngeal manifestations of gastroesophageal reflux disease: endoscopic
      appearance and management.

PMID- 8857140
TI  - A new way to obtain contrast-free bile during ERCP.

PMID- 8857141
TI  - Peroral cholangioscopy using new fine-caliber flexible scope for detailed
      examination without papillotomy.

PMID- 8857142
TI  - A new biopsy handle instrument for endoscopic ultrasound-guided fine-needle
      aspiration biopsy.

PMID- 8857143
TI  - Laparoscopic Taylor procedure in Chinese patients.

PMID- 8857144
TI  - Endoscopic injection of gelatin solution for severe hemorrhagic gastric cancer.

PMID- 8857145
TI  - Bleeding from bile duct varices: an unexpected hazard during therapeutic ERCP.

PMID- 8857146
TI  - A new approach to sphincterotomy in patients with Billroth II gastrectomy.

PMID- 8857147
TI  - How big is too big?

PMID- 8857148
TI  - Stents, cloggology, and esophageal cancer.

PMID- 8857149
TI  - Does using a warmer influence the results of rapid urease testing for
      Helicobacter pylori?

PMID- 8857150
TI  - Retrieval of a pin from the stomach by endoscopic aspiration through an inner
      tube.

PMID- 8857152
TI  - Simple method for making triple-lumen needle-knife papillotome.

PMID- 8857151
TI  - Another approach to the buried bumper syndrome.

PMID- 8857153
TI  - An improved approach to delivery of enteral nutrition in the intensive care unit.

PMID- 8857154
TI  - Poor result after insertions of multiple esophageal metal stents in the cervical
      esophagus.

PMID- 8857155
TI  - Key issues affecting school-based health centers and Medicaid.
AB  - Public support for establishing school-based health centers has outstripped
      understanding of how to pay for them in the long term. As a result, a large
      number of school-based health centers have been started without a clear notion of
      how they will be sustained. Since 1990, the number of school-based health centers
      has grown from an estimated 200 to almost 700. A substantial portion of these
      centers face staffing and service cuts if stable funding mechanisms to support
      school-based health centers are not put into place. This article addresses issues
      raised as state governments and the centers consider the possibility of patient
      care revenue as a component of a long-term funding strategy.

PMID- 8857157
TI  - Medicaid reimbursement for school nursing services: a position paper of the
      National Association of State School Nurse Consultants.
AB  - The National Association of State School Nurse Consultants (NASSNC) believes that
      school nursing services should be provided to all students and that Medicaid
      funds should be incorporated as a funding source for school nursing services
      provided to eligible children. The list of nursing services and procedures in
      this document, therefore, should be reimbursable by Medicaid to school districts.
      These services are outlined in categories of 1) case finding, 2) nursing care
      procedures, 3) care coordination, 4) patient/student counseling/instruction, and
      5) emergency care. We adhere to this philosophy and promote incorporation of
      these services as Medicaid reimbursable services provided by qualified
      professional school nurses.

PMID- 8857156
TI  - Safer Choices: a multicomponent school-based HIV/STD and pregnancy prevention
      program for adolescents.
AB  - Given the serious consequences of HIV infection, other STDs, and pregnancy among
      teens, professionals must develop and evaluate new approaches to reduce risks
      associated with adolescent sexual behavior. The Safer Choices intervention is a
      comprehensive, theoretically based program designed to reduce risk behaviors and
      increase protective behaviors to prevent HIV, other STDs, and pregnancy among
      high school adolescents. The program includes five components: a School Health
      Promotion Council involving administrators, school staff, students, parents, and
      community members; curriculum and staff development activities; school
      environment activities designed and implemented by a team of peer educators;
      parent education activities; and school-community linkage activities. The School
      Health Promotion Council is responsible for planning and overseeing program
      implementation. This article describes the theoretical framework, process for
      intervention development, and key intervention strategies used in Safer Choices.

PMID- 8857158
TI  - Sexual risk-taking by Muscovite youth attending school.
AB  - Sexual behaviors of adolescents place them at a high risk for HIV and other
      sexually transmissible infections. Studies of sexual risk-taking and other health
      compromising practices by youth in countries other than the United States are
      relatively rare. Examination of health practices across cultures provides
      insights with respect to explaining international differences in disease rates,
      helps predict future trends in disease transmission, and identifies health
      education needs of particular populations or settings. Sexual behavioral risk
      factors were studied in a sample of 1,090 youth (mean age = 14 years) in Moscow
      using a translated version of the Youth Risk Behavior Surveillance (YRBS) survey
      developed by the U.S. Centers for Disease Control and Prevention. Only 26.3% of
      Muscovite youth report being taught about HIV/AIDS infection in school, and just
      41.7% indicate discussion of HIV/AIDS occurred with parents or other familial
      adults. Overall, 15.7% of females and 23.7% of males report at least one sexual
      intercourse in their lifetime. About 8.8% of the sample reported participation in
      sexual intercourse before age 12, and 34.9% indicated having had sexual
      intercourse with four or more partners. Concomitant use of alcohol and other
      drugs is common (24.4%) prior to the most recent intercourse, and use of a condom
      occurs in fewer than half (41.7%) of recent sexual episodes.

PMID- 8857159
TI  - The Youth Health Survey: reliability and validity of an instrument for assessing
      cardiovascular health habits in adolescents.
AB  - The Youth Health Survey (YHS) was developed as part of a school-based
      longitudinal study (Cardiovascular Health in Children and Youth) to assess and
      track behavior and attitudes related to cardiovascular risk factors in children
      and adolescents. This paper reports the psychometric properties of each of the
      subscales of the YHS and the results of a pilot study with sixth, seventh and
      eighth grade students (n = 205) at two schools in the Southeast. The eight
      subscales of the YHS assess health habits and attitudes of the adolescent as well
      as selected peer and family influences on those health behaviors. Internal
      consistencies for seven of the eight subscales ranged from .74 to .89. Test
      retest reliability for six of the eight subscales ranged from .67 to .89.
      Construct validity was established through factor analyses of four of six of the
      subscales. Findings support using the YHS with some minor revisions to assess
      behaviors, attitudes and influences which may lead to CVD in adulthood.

PMID- 8857160
TI  - Black and white adolescent females' perceptions of ideal body size.
AB  - A stratified, random sample of 344 White and Black adolescent females
      participated in a survey of ideal body size beliefs, which included responses to
      a questionnaire and a series of nine female and male body size drawings. Using
      SES and race as independent variables and BMI (kg/m2) as a covariate. Black
      females preferred a significantly heavier ideal female body size than Whites.
      They also perceived their parents and both male and female friends would select
      as ideal a significantly heavier female body size than White subjects. Black
      subjects' body size preferences were significantly more influenced by family
      members than were White subjects, who were significantly more influenced by their
      peer group. These findings suggest a greater social approval of increasing weight
      and body size for Black adolescent females, a desire for a smaller size by White
      adolescent females, and cultural differences in the influencing factors that help
      to communicate these body size preferences.

PMID- 8857161
TI  - Connecting nutrition and mathematics: the 5-A-Day for Better Health Plan.

PMID- 8857162
TI  - [Clinical feature of dementia of the Alzheimer type].
AB  - Dementia of the Alzheimer type (DAT) is a disorder in the elderly, showing
      progressive decline of memory and various cognitive functions. There is no known
      effective treatment for DAT. Symptoms appear gradually and the course is steadily
      progressive. Neuropathologically, limbic and posterior association cortices of
      the cerebrum are preferentially affected. Abundant neuritic plaque,
      neurofibrillary tangles, and neuronal loss are detected in these areas. DAT is
      one of major disorders among senile dementia, frequent next to vascular dementia,
      in the Japanese. According to the age at onset, DAT has been classified into
      Alzheimer's disease (age at onset < or = 65) and senile dementia of Alzheimer
      type (age at onset >65). However, the rate of progression and clinical severity
      differ in these two groups, indicating that etiology of DAT is heterogeneous
      [correction of heterogenous]. Clinical diagnosis of DAT is mostly based on
      symptoms, mode of progression, and neuropsychiatric evaluation. DSM-IV has been
      recommended as a standard criteria. X-ray CT or MR imaging study can estimate
      atrophic alteration of DAT brain, and is of value in the differential diagnosis.
      In addition, PET or SPECT are useful tools for evaluating functional deficits of
      the cerebral cortex, since such abnormalities can be detected even from an early
      stage. Recent molecular genetic studies have disclosed that genetic background of
      DAT is heterogeneous [correction of heterogenous]. Not only mutation in a
      causative gene but also certain predisposing genes play roles in generating DAT
      pathology. However, it is still uncertain whether such genetic factors are
      correlated with the divergence of DAT phenotype.

PMID- 8857163
TI  - [Biological characteristics of amyloid precursor protein and Alzheimer's
      disease].
AB  - Recent advances in Alzheimer's disease (AD) research were briefly reviewed. AD is
      the most common cause of progressive intellectual decline in the aged in the
      Western world and also in Japan. The AD-affected brain is characterized by
      numerous amyloid plaques, neurofibrillary tangles, and neuronal losses. The
      amyloid deposition is considered to be more important because it appears first,
      and is followed by NFTs. The amyloid is composed of amyloid beta peptide (Abeta),
      a 40 approximately 42 amino acid fragment of the large membrane protein, amyloid
      precursor protein (APP). Abeta is cleaved by the proteolytic enzymes, beta, and
      gamma secretase. Considerable effort has been directed to identify these enzymes,
      and to find the intracellular compartments where Abeta is generated. The
      lysosome, or related acidic compartment is one of the candidates. The N and C
      terminis of the Abeta is known to vary slightly. Biochemical and
      immunopathological studies implicate that Abeta42 is more important than Abeta40
      in the pathogenesis of AD. On the other hand, many missense mutations in APP gene
      and other genes, e.g. S182, and STM 2 have been identified in familial AD.
      Neuropathologically, AD is regarded as cerebral Abeta amyloidosis. The AD amyloid
      is composed of many proteins other than Abeta, designated as amyloid associated
      proteins. These proteins may play important roles in amyloid formation, since
      Abeta itself is soluble. Transgenic mice and chloroquine myopathy rat are
      available as animal models for AD. Elucidation of the roles of these missense
      mutations, and amyloid associated proteins in the cascade of AD, may provide a
      breakthrough to therapeutics for AD.

PMID- 8857164
TI  - [A comparative study on histopathological findings between Alzheimer's disease
      and senile dementia of Alzheimer type].
AB  - Histopathological findings of the brains in 2 cases of Alzheimer's disease (AD)
      were comparatively studied with those in 2 cases of senile dementia of
      Alzheimer's type (SDAT). Marked atrophy of the temporal lobe, most conspicuous at
      the hippocampus and entorhinal cortex was commonly observed in all 4 cases.
      Microscopic examination revealed in the AD cases various forms of senile plaques
      including those of primitive type or ones with an amyloid core, while plaques in
      the cases of SDAT were mostly composed of non-typical forms without an amyloid
      core. The senile plaques and neurofibrillary tangles (NFT) were widely
      distributed in the neocortices such as in the frontal, parietal and occipital
      lobes as well as in the hippocampal and parahippocampal gyri in the cases of AD,
      while the density of SPs in the neocortices was lower than that in the
      hippocampal and parahippocampal gyri, and NFTs were scarcely observed in the
      neocortices in the cases of SDAT. This suggests that we should
      histopathologically differentiate SDAT from AD, although we found no marked
      macroscopic differences between the AD brain and SDAT brain.

PMID- 8857165
TI  - [Physiology and pathology of the lipid transport in the brain].
AB  - Apolipoprotein E is the major lipid carrier protein in the brain. This protein is
      contained in HDL1-like particles in human and rat cerebrospinal fluid.
      Cerebrospinal fluid apolipoprotein metabolism is resistant to the alteration in
      plasma lipoprotein metabolism and to age-related changes. In a patient with
      multiple sclerosis, immunoreactive apolipoprotein E was seen in astrocytes and
      macrophages in the brain section with a pathological change, indicating that
      apolipoprotein E has a significant role in the lipid redistribution process after
      demyelination. The epsilon4 allele is more frequent in Japanese patients with
      Alzheimer's disease than in control, as well as Caucasians, suggesting the
      significant contribution of the epsilon4 allele to the pathogenesis of the
      disease.

PMID- 8857166
TI  - [Reference intervals, discussed again].
AB  - The concept of 'reference intervals' proposed by NCCLS DOCUMENT C28-P has been
      introduced in Japan, and it has been widely accepted among laboratory scientists
      and clinicians. However, the terms 'reference values' and 'reference intervals'
      appear to be misunderstood by some. Normal ranges which have been used
      conventionally should not be simply renamed 'reference intervals'. The term
      'reference intervals' should be strictly reserved for the ones which are
      determined based on the NCCLS recommendation. However, it is not an easy work,
      almost impractical for most clinical laboratories to follow strictly the NCCLS
      document C28-P. Therefore, the author suggests [correction of suggest] a multi
      institutional cooperative activity to establish the reference intervals; the
      reference intervals for 13 serum proteins among Japanese adults have been
      successfully determined with the cooperative work of 7 clinical laboratories.
      'Reference values' in a strict sense has been defined by NCCLS to be the observed
      values among reference individuals. However, 'reference values' in a broad sense
      should be understood to be any consensus value set by a professional group(s) for
      the purpose of clinical decision making.

PMID- 8857167
TI  - [Practical subjects of reference interval].
AB  - A concept of reference interval was first proposed by Dybkaer in 1973 in order to
      avoid an ambiguous definition of so-called normal range. This concept was
      succeeded by IFCC Expert Panel on Theory of Reference Value and the
      recommendation for the concept of reference value was documented in 1987 from
      IFCC scientific committee. Finally, NCCLS proposed the document for Reference
      Interval, how to determine, utilize the reference interval in clinical
      laboratory, in 1992. In this paper, how to determine and utilize the reference
      interval in clinical laboratory are described and discussed based on the concepts
      of NCCLS and IFCC.

PMID- 8857168
TI  - [Derivation of latent reference intervals from routine laboratory database: its
      principle, validity and methodological implications for laboratory informatics].
AB  - A new method to derive reference from routine laboratory database intervals was
      developed. It depends on (1) availability of multiple screening tests results,
      (2) initial estimates for the reference intervals (RI) and (3) exclusion of data
      with multiple abnormalities in "related" test items. We designated those data
      which remained after exclusion as "latent reference values". RI was calculated
      from them parametrically employing a modified Box-Cox power transformation and
      maximal likelihood method. After RI were derived for all the items, they were
      used as a new set of RI estimates and the series of exclusion/calculation
      procedures were repeated for 7 times. The validity of the latent reference
      intervals (LRI) derived from routine biochemical screening test results were
      evaluated in three ways, by comparing them (1) with RIs determined conventionally
      from healthy individuals, and (2) with LRIs derived from qusi-normal individuals
      (blood donors), and (3) with LRIs obtained from a simulated healthy population
      which was generated as multivariate normal random values.

PMID- 8857169
TI  - [Pathogenesis-screening tests for liver dysfunction in the asymptomatic patients
      with elevated ALT values and their diagnostic efficacies in primary care
      medicine].
AB  - We have evaluated the diagnostic efficacies of ultrasonography and hepatitis C
      virus (HCV) antibody measurement to differentiate pathogenesis of liver
      dysfunction in the asymptomatic adults with elevated ALT value. Among 4256
      visitors to PL Tokyo Health Control Center for their health examination, 463
      cases (11%) showed abnormal liver function including elevation of ALT value.
      Ultrasonography and HCV antibody measurement using the second generation reagent
      had been applied to 362 cases in order to screen the etiology of liver
      dysfunction. The ultrasonography succeeded to establish the diagnosis of fatty
      liver in 137 cases (38%) and 41 cases (11%) demonstrated positive HCV antibody.
      There were 4 cases with positive HBs antigen, however, it was found that their
      abnormal liver function was attributed to other etiology such as fatty liver and
      alcoholic liver dysfunction rather than chronic type B hepatitis. HCV antibody
      positive cases showed higher levels of total protein, ZTT, AST, ALT, and lower
      levels of albumin, A/G, total cholesterol, triglyceride, gamma-GT and
      cholinesterase value than other cases. HCV antibody titers were not correlated to
      hepatic parenchymal damage estimated by ALT or cholinesterase value. Only a
      little correlation was observed between HCV antibody titers and HCV-RNA amounts
      determined by the competitive reverse transcription-polymerase chain reaction (RT
      PCR) method. These results indicate sufficient diagnostic efficacies of
      ultrasonography and HCV antibody measurement for a pathogenesis differentiation
      in the asymptomatic patients with liver dysfunction, and these examinations
      should be employed as the first-step screening tests for the etiology
      determination of liver diseases in the primary care medicine.

PMID- 8857170
TI  - [Direct detection of human cytomegalovirus in urine specimens from bone marrow
      transplant patients by polymerase chain reaction].
AB  - Human cytomegalovirus (HCMV) infection is a major causative life-threatening
      agent that results in opportunistic infections in bone marrow transplant
      patients. Since antiviral therapy is available for severe HCMV infections,
      methods to rapidly identify infected patients are needed so that therapy can be
      promptly instituted. In this study, we used direct method to detect HCMV in urine
      specimens by nested polymerase chain reaction (nested-PCR) to monitor urinary
      excretion of HCMV in patients undergoing bone marrow transplantation. The viral
      DNA was amplified directly from preheated urine without further treatment prior
      to amplification. Five microliter of urine proved to give the most efficient
      amplification. The detection limit of the PCR assay for detection of HCMV was 10
      copies/microl. The positive rate of the PCR assay and the tissue culture method
      for detection of HCMV were 15 of 61 (24.6%) and 4 of 61 (6.6%), respectively.
      Sensitivity and specificity of the PCR assay were 100% and 81% respectively.
      Based on these data, urinary excretion of HCMV in 21 patients undergoing bone
      marrow transplantation were monitored weekly by the PCR assay. As a result, in
      addition to a higher sensitivity, the PCR assay allowed to identify HCMV
      infection 3.1 (1 approximately 5) weeks earlier than culture method or antibody
      elevation. Repeated monitoring of virus excretion by this rapid and simple method
      was useful to promptly detect HCMV infection, allowing proper institution of
      antiviral drug therapy in patients undergoing bone marrow transplantation.

PMID- 8857171
TI  - [Median nerve somatosensory evoked potentials--studies on latency variability as
      a function of subject height and age].
AB  - Somatosensory evoked potentials (SEP) to median nerve stimulation were studied in
      a group of 61 healthy volunteers (36 men, 25 women) between 15 and 79 years of
      age. The absolute peak latencies of peripheral N9, Erb, cervical N11 and N13,
      cortical N20, N32 and N60 were analyzed as a function of height and age. Three
      interpeak latencies, Erb-N13, Erb-N20 and N13-N20, were equally studied. There
      was no gender difference in the latencies and interpeak latencies of SEP in
      multiple correlation analysis involving height and age. Multiple regression
      analysis showed that except for N60 peak latency, the subject's height and age
      provided better prediction of other SEP latencies, and Erb-N13 and Erb-N20
      interpeak latencies than simple and polynomial [correction of polynominal] linear
      regression. Multiple regression analysis was found to provide better optimal
      clinical upper limits for individual SEP latencies and interpeak latencies, and
      may increase the diagnostic sensitivity. The t-value of the multiple regression
      coefficient for standardized height and standardized age showed that the effects
      of age on N32 and N60 peak latencies, and on Erb-N13 and Erb-N20 interpeak
      latencies were a more important factor than those of height. A negative
      correlation was found between height and age in our subjects. Although this may
      be a characteristic of modern Japanese, it suggests the necessity of renewing
      regression models at intervals of 5 or 10 years.

PMID- 8857172
TI  - [Discrepancy of CAP survey results on urinary sediment between all participants
      and Japanese participants].

PMID- 8857173
TI  - [Report of Ad hoc Lp(a) Standardization Subcommittee in Standardization Committee
      of the Japan Society of Clinical Pathology. I. Summary of the results of
      questionnaire to the Lp(a) test reagent markers].

PMID- 8857174
TI  - [Report of Ad hoc Lp (a) standardization subcommittee in Standardization
      Committee of the Japan Society of Clinical Pathology. II. Results of the survey
      for the correction of-inter-laboratory variations by the unified reference
      material].

PMID- 8857175
TI  - The distribution of West Virginia women targeted for screening of breast and
      cervical cancers.
AB  - The primary strategy for the control of female breast and cervical cancers is
      early diagnosis and treatment from periodic screenings. To effectively provide
      screenings, it is important to target the populations that especially need these
      services. Based on state health objectives and an analysis of data from the 1990
      Census, about 33% of the women in West Virginia are targeted for routine
      screening for breast cancer by clinical breast examination and mammograms, while
      about 77% are targeted for routine screening for cervical cancer by the
      Papanicolaou test. Since the racial and age distributions of women vary across
      Public Health Management Districts in the state, it is critical to determine the
      exact extent of breast and cervical cancers in West Virginia for geographic and
      other populations of women. In addition, the results demonstrate a need for age
      adjustment when comparing measures of the cancers across geographic areas.

PMID- 8857176
TI  - The difficult diagnosis of subdural empyema: report of three cases and review of
      the literature.
AB  - Subdural empyema remains a frequently misdiagnosed clinical entity. This article
      presents three cases of subdural empyema and a review of recent literature.

PMID- 8857177
TI  - Enhanced limb salvage for peripheral vascular disease with the use of spinal cord
      stimulation.
AB  - For patients with peripheral vascular disease that have exhausted all means for
      surgical repair, spinal cord stimulation is an alternative treatment that could
      offer them significant pain relief or possibly delay the need for limb
      amputation. Spinal cord stimulation (SCS) has proven to offer many of these
      patients a return to a more normal lifestyle by relieving pain to such a degree
      that their mobility is improved. In addition, increases in blood flow to the
      affected extremity have helped to improve overall foot salvage. Since SCS is
      minimally invasive and has few reported complications, it is a viable alternative
      for patients with multiple health risks, and with proper patient selection and
      early referral, it can reduce health care costs in many cases.

PMID- 8857178
TI  - Granuloma of the lacrimal sac.
AB  - This article describes a rare case of granuloma of the lacrimal sac, which was
      treated with dacryocistorhinostomy and glabellar flap. In addition, the possible
      etiologic factors, the differential diagnosis and reconstructive techniques
      indicated in such cases are described.

PMID- 8857179
TI  - Stereoselective metabolic pathways of ketoprofen in the rat: incorporation into
      triacylglycerols and enantiomeric inversion.
AB  - The enantiomeric bioinversion of ketoprofen (KP) enantiomers and their
      incorporation into triacylglycerols were investigated in the rat (1) in vitro,
      using liver homogenates, subcellular fractions, and hepatocytes, and (2) in vivo,
      in different tissue samples after oral administration of the radiolabelled
      compounds. In liver homogenates or subcellular fractions, the enantiomer (S)
      ketoprofen (S-KP) was recovered unchanged, whereas (R)-ketoprofen (R-KP) was
      partially converted into its Coenzyme A (CoA) thioester and inverted to S-KP.
      Both processes occurred mainly in the mitochondrial fraction. This supports the
      mechanism of inversion via stereoselective formation of CoA thioester of R-KP,
      already described for other non-steroidal anti-inflammatory drugs. Incorporation
      into triacylglycerols was detected after incubation with intact hepatocytes in
      the presence of added glycerol. The process was stereoselective for R-KP vs. S-KP
      (covalently bound radioactivity 26,742 +/- 4,665 dpm/10(6) cells vs. 6,644 +/-
      3,179 dpm/10(6) cells, respectively). However, no incorporation was found in
      liver samples after oral administration of either R-KP or S-KP. On the contrary,
      in adipose tissue samples a significant and stereoselective formation of hybrid
      triacylglycerols was observed: 11,076 +/- 2,790 dpm.g-1 for R-KP vs. 660 +/- 268
      dpm.g-1 for S-KP. The incorporated R/S ratio, higher in adipose tissue (R/S = 17)
      than in hepatocytes (R/S = 4), indicates that fat may be the main tissue store
      for the xenobiotic R-KP in rats.

PMID- 8857180
TI  - Copper(II) complexes of N2-alkyl-(S)-amino acid amides as chiral selectors for
      dynamically coated chiral stationary phases in RP-HPLC.
AB  - Copper(II) complexes of N2-octyl-(S)-phenylalaninamide (Noc-Phe-NH2), N2-dodecyl
      (S)-phenylalaninamide (Ndo-Phe-NH2), and N2-octyl-(S)-norleucinamide (Noc-NLeu
      NH2), dynamically adsorbed on a reversed-phase C18 column, were able to perform
      the direct enantiomeric separation of unmodified amino acids, amino acid amides
      and esters, hydroxy acids, and dipeptides by elution with aqueous or mixed
      aqueous-organic solutions containing copper(II) sulphate or acetate. The role
      played by several parameters in the separation procedure was examined with the
      copper(II) complex of Noc-Phe-NH2 [concentration of the copper(II) ion in the
      eluent, pH and eluent polarity, amount of adsorbed selector]. The separation was
      shown to occur entirely on the stationary phase. The mechanism of chiral
      discrimination is discussed in terms of the chromatographic parameters and of the
      structure of the copper(II) complexes in solution and in the solid state. The
      chiral stationary phase maintained its separation ability for about 3 months.
      However, the column could be easily restored by recovering the selector with
      methanol and repeating the loading procedure.

PMID- 8857181
TI  - Stereoselective binding of carbenicillin epimers to human serum albumin.
AB  - Binding of carbenicillin (CBPC) epimers to human serum albumin (HSA) was found to
      be stereoselective. Epimer-epimer interaction was also observed in the binding to
      HSA. There were at least three binding sites on HSA for CBPC epimers, one of
      which (stereoselective site) was more in favor of S-CBPC than R-CBPC. At the
      stereoselective site, the binding constant of S-CBPC was approximately 4-fold
      greater than that of R-CBPC. The affinities to other binding sites (non
      stereoselective sites) were similar between the epimers, and the affinity of S
      CBPC of the non-stereoselective sites was much smaller than that for the
      stereoselective site. R-CBPC and S-CBPC appeared to displace each other at all
      the binding sites, i.e., the binding of the epimers was competitive at the non
      stereoselective sites as well as at the stereoselective site. By using site
      marker ligands, it was revealed that CBPC epimers may bind to Site I (warfarin
      binding site), but not to Site II (diazepam binding site). A binding model with
      an assumption of competitive interactions at all the binding sites simulated the
      binding characteristics of CBPC epimers fairly well.

PMID- 8857182
TI  - Disposition of CS-670, a novel nonsteroidal anit-inflammatory drug, and its
      metabolites in healthy human volunteers.
AB  - CS-670, a novel nonsteroidal anti-inflammatory drug, is a racemic prodrug. Plasma
      concentrations and urinary excretion of CS-670 and its metabolites were
      determined in experimental subjects after oral administration at a single 120 mg
      dose. CS-670 and four metabolites, the saturated ketone (M-A), unsaturated
      alcohol (M-B), cis-alcohol (M-C), and trans-alcohol (M-D), were quantitated by GC
      MS. The major metabolites in human plasma were M-B, M-C, and M-D and their
      terminal half-lives (t1/2) were 0.9, 2.6, and 1.2 h, respectively. The total
      recovery in the urine was 26% of the dose, but unchanged CS-670 accounted for
      less than 2% over a 48 h period. In addition, the absolute configurations of the
      metabolites were examined by HPLC after derivatization with chiral reagents. It
      was found that the configuration of the propionic acid moiety of the metabolites,
      M-B, M-C, and M-D, in human plasma, was rapidly inverted from (-)-(R) to the (+)
      (S) configuration in stereoselective biotransformation. Furthermore, the
      configurations of the 1'- and 2'-carbons of M-C and M-D, were found to be (1'R,
      2'S) and (1'R, 2'S), respectively. These results show that CS-670 is readily
      biotransformed by chiral inversion of the 2-arylpropionic acid moiety and
      stereoselective reduction of the alpha, beta-unsaturated ketone moiety in humans.

PMID- 8857183
TI  - Stereoselective nucleophilic substitution of oxazepam and racemization in acidic
      methanol and ethanol.
AB  - Enantiomeric and racemic oxazepam (OX), 3-O-methyloxazepam (MeOX), and 3-O
      ethyloxazepam (EtOX) were used to study racemization, heteronucleophilic, and
      homonucleophilic substitution reactions in anhydrous acidic methanol and ethanol.
      Kinetics of racemization and nucleophilic substitution reactions in nondeuterated
      and deuterated solvents were determined by circular dichroism spectropolarimetry,
      chiral stationary phase high-performance liquid chromatography (HPLC), reversed
      phase HPLC, and mass spectrometry. Several reactions occurred when (S)-OX, for
      example, was dissolved in acidic methanol: (1) (S)-OX itself underwent
      spontaneous racemization, (2) the 3-hydroxyl group of (S)-OX was
      stereoselectively substituted by the methoxy group of methanol to form MeOX
      enriched in (S)-MeOX, and (3) the 3-methoxy group of (R)-MeOX was
      stereoselectively substituted by the methoxy group of methanol to form MeOX
      enriched in (S)-MeOX, and (4) the 3-methoxy group of (R)-MeOX was
      stereoselectively substituted by the methoxy group of methanol to form MeOX
      enriched in (R)-MeOX. Repetitive reactions 3 and 4 eventually resulted in a
      racemic MeOX. Similar reactions occurred for an enantiomeric OX in acidic
      ethanol.

PMID- 8857184
TI  - Adsorption of protein from several commercial lipase preparations onto a hollow
      fiber membrane module.
AB  - Ten commercially available crude preparations of lipase from various microbial
      sources were adsorbed from aqueous buffers at several initial concentrations onto
      a bundle of hydrophobic hollow fibers made of poly(propylene) at pH 7.0 and 40
      degrees C. The kinetics of adsorption were evaluated from measurements at various
      times of the protein content of the supernatant solution (using BSA as
      equivalent) in a well-mixed reservoir placed in series with the hollow fiber
      module. Preliminary tracer experiments have indicated that the module and the
      tank can be simulated as a system consisting of a plug flow reactor in series
      with a continuous stirred tank reactor. A mechanistic model based on the
      hydrodynamic assumptions associated with this system coupled with the postulation
      of two reversible first-order steps for the adsorption of protein was
      successfully fitted to the experimental data via nonlinear regression analysis.
      The statistical significance of the model was checked using tests for lack of
      fit. This work is useful in predicting the time period required to immobilize a
      (crude) lipase by adsorption onto a hydrophobic hollow fiber module, a
      configuration which has proved successful in the recent past for the performance
      of lipase-catalyzed reactions.

PMID- 8857185
TI  - Influence of polymer structure on protein partitioning in two-phase aqueous
      systems.
AB  - Copolymers of acrylamide and styrene with two distinct structures were
      synthesized to study the effect of polymer structure on protein partitioning in
      two-phase aqueous systems. Micellar copolymerization was used to prepare a
      multiblock copolymer, while homogeneous copolymerization was used to prepare a
      random copolymer, both with the same composition and molecular weight. Phase
      behavior studies of the copolymers with poly(ethylene glycol) in water showed
      little difference in the phase boundaries. However, the partitioning of bovine
      serum albumin between the two aqueous phases was sensitive to the polymer
      structure. A molecular picture is proposed for the interactions between the
      protein and block copolymers. The effect of pH on the protein partition is
      analyzed in terms of the hydrophobic interactions, and the polymer and protein
      partitioning was correlated using a model based on the Flory-Huggins theory.

PMID- 8857186
TI  - Chromatography for rapid buffer exchange and refolding of secretory leukocyte
      protease inhibitor.
AB  - A DEAE-cellulose stationary phase in a rolled configuration was used to separate
      recombinant secretory leukocyte protease inhibitor (rSLPI) from denaturants and
      reducing agents (3 M guanidine-HCl and 5 mM DTT) in less than 5 min to promote
      refolding of the protein to an active form. The mobile phase consisted of buffer
      and 500 mM NaCl, where NaCl suppressed binding of protein to this stationary
      phase. Separation of an initial concentration of 2 mg/mL protein from the other
      constituents resulted in 96% recovery of the rSLPI at an average concentration of
      1.28 mg/mL. When incubated for 4 h at 20 degrees C, the fractionated rSLPI gave a
      46% yield of properly refolded protein. The protein concentration was 6.4 times
      higher than that reported in a previously published method, where refolding was
      carried out by diluting the mixture of protein, denaturants, and reducing agents
      by a factor of 10. The results show that a combination of rapid chromatographic
      separation over a cellulosic stationary phase followed by protein refolding will
      significantly enhance process throughput by minimizing tankage, water
      requirements, and process time.

PMID- 8857187
TI  - Cell segregation and lysis have profound effects on the growth of Escherichia
      coli in high cell density fed batch cultures.
AB  - Cell segregation into nondividing states and lysis was found to dominate the
      growth behavior of high cell density fed batch cultures of Escherichia coli. When
      the specific growth rate declined below a critical value, the biomass production,
      oxygen consumption, and carbon dioxide formation rates declined sharply.
      Concomitantly, an extensive loss of colony-forming ability (cfu) and accumulation
      of extracellular proteins was observed. A segregated model that considered
      different physiological states, including dividing, nondividing, and lysed cells,
      was developed and applied to experimental data from high cell density cultures of
      E. coli.

PMID- 8857189
TI  - Optimization study of Escherichia coli TB1 cell disruption for cytochrome b5
      recovery in a small-scale bead mill.
AB  - The recovery of a recombinant intracellular protein, cytochrome b5, from
      Escherichia coli TB1 cells was carried out by bead mill disintegration in a
      discontinuous small-scale instrument. This process was optimized by the use of
      experimental factorial design. Several parameters were studied: operating time,
      amount and size of beads, cellular suspension concentration, and presence of
      toluene and lysozyme. For the experimental conditions used, only the time of
      treatment and bead load had significant effects. The optimal values of these
      variables were found by applying the response surface methodology.

PMID- 8857188
TI  - Synthesis rates of cellular proteins involved in translation and protein folding
      are strongly altered in response to overproduction of basic fibroblast growth
      factor by recombinant Escherichia coli.
AB  - The cellular response to temperature-induced production of human basic fibroblast
      growth (bFGF) factor by recombinant E. coli (bacteriophage lambda PRPL
      promoter/cI857 repressor expression system) was studied by one- and two
      dimensional gel electrophoresis. Temperature shift from 30 to 42 degrees C caused
      the induction of heat-shock protein synthesis and the repression of synthesis of
      ribosomal proteins and the protein folding catalyst trigger factor. Compared to
      control cells, carrying the expression vector without structural bFGF gene cells,
      producing the heterologous protein exhibited a stronger increase in the synthesis
      rate of heat-shock proteins ClpB (HtpM), DnaK, HtpG, GroEL, GrpE, and IbpB (HtpE)
      in response to temperature upshift. Unexpectedly, formation of the chaperone heat
      shock protein GroES was not detected after temperature shift to 42 degrees C in
      cells producing bFGF. In addition to amplified heat-shock protein formation, the
      syntheses of ribosomal proteins and of the protein folding catalyst trigger
      factor were more severely repressed after temperature upshift in cells producing
      bFGF. In conclusion, the normal cellular stress response caused by the high
      inducing temperature was strongly amplified by heterologous protein synthesis. In
      particular, syntheses of proteins involved in translation and protein folding
      were affected by the overproduction of the heterologous protein.

PMID- 8857190
TI  - Effects of glycerol of beta-lactamase production during high cell density
      cultivation of recombinant Escherichia coli.
AB  - Recombinant Escherichia coli was cultured up to OD600 90 with glycerol fed by the
      DO-STAT method to produce recombinant beta-lactamase. Optimum feeding and
      induction conditions were determined. When glycerol was maintained at a high
      concentration (40-50 g/L) after isopropyl thiogalactoside (IPTG) induction at
      OD600 75, a 2-fold increase in the amount of soluble beta-lactamase was obtained.
      Similarly, a 3-fold increase was obtained by the addition of NaCl (0.4 M) at low
      glycerol concentration (10 g/L).

PMID- 8857191
TI  - Analysis of nutritional factors and physical conditions affecting growth and
      monoclonal antibody production of the hybridoma KB-26.5 cell line.
AB  - The effect of medium composition and physical conditions on the growth pattern
      and monoclonal antibody production of the hybridoma cell line KB-26.5 has been
      studied in batch and fed-batch cultures. Different aspects have been analyzed
      both individually and in combination, as it is expected that not only one
      component plays a predominant role in this process but a combination of a number
      of them. Modification of the concentrations of glucose and glutamine,
      supplementation of the medium with vitamins and amino acids, influence of lactate
      and ammonium accumulation, and pulse addition of fetal calf serum have been
      studied in detail, contributing to an improvement in the cell growth and IgG3
      production. Finally, the combined effect of all these factors in a fed-batch
      culture leads clearly to a major improvement in the cultures, with a 10-fold
      increase in the final monoclonal antibody concentration with respect to
      nonoptimized batch experiments.

PMID- 8857192
TI  - Binding of antithrombin III and thrombin to immobilized heparin under flow
      conditions.
AB  - The chemical immobilization of heparin onto polymeric materials through
      hydrophilic spacer groups was performed to improve the hemocompatibility of blood
      contacting devices. Significant data have been gathered attesting to the
      biological activity of immobilized heparin in static in vitro studies (clotting
      times) and dynamic in vivo studies (thrombus formation). However, few studies
      have been performed to investigate the binding kinetics of spacer-immobilized
      heparin under flow (shear stress) with antithrombin III (ATIII) and thrombin. To
      help elucidate this binding mechanism, a mathematical model was developed which
      parallels experiments to measure protein binding and dissociation at the heparin
      immobilized surface under flow conditions. Heparinized tubing was prepared by
      chemically immobilizing a high-ATIII-affinity fraction of heparin onto the
      surface of poly(ethylene)-oxide grafted, poly(styrene-co-p-aminostyrene)-coated
      polyethylene tubing. ATIII was first bound onto the immobilized heparin, followed
      by the introduction of thrombin to interact with ATIII. The concentration of
      thrombin-ATIII complex (TAT) flowing from the tubing was determined, and the
      dissociation rate constants (kD) of TAT from immobilized heparin were calculated
      as a function of flow rate. The results indicate that the dissociation rate
      constant of TAT varied with flow rate, especially low flow rates, high flow
      rates, and turbulent flow. As the TAT complex dissociates from immobilized
      heparin, this "recovered" heparin is available for subsequent binding of more
      ATIII and thrombin. These in vitro mathematical results may help support
      mechanisms and hypotheses generated for the biological activity of spacer
      immobilized heparin observed during long-term in vivo and ex vivo experiments.

PMID- 8857193
TI  - Growth and induction kinetics of inducible and autoinducible expression of
      heterologous protein in suspension cultures of recombinant mouse L cell lines.
AB  - Mouse Ltk- cells were transfected with four different plasmids for autoinducible
      and highly-inducible expression of the bacterial lacZ gene and cultivated in
      suspension. Two selection genes, thymidine kinase (tk) and neomycin resistance
      (neor), were used to select the clones in both cell lines. The resulting two cell
      lines, designated M4 and R2, differ in that the inducible MMTV promoter from
      mouse mammary tumor virus (MMTV) controls glucocorticoid receptor (gr) gene and
      lacZ gene expression in the M4 cell line ("autoinducible"), while the
      constitutive rous sarcoma virus (RSV) promoter controls gr gene expression and
      the MMTV promoter controls lacZ gene expression in the R2 cell line ("highly
      inducible"). Both cell lines were stable with respect to reproducibility of
      growth rate in spinner flasks and inducibility of beta-galactosidase expression.
      The exponential growth rate of R2 cells was slower than that of M4 cells before
      induction because the R2 cell line continuously expressed gr genes under the
      constitutive RSV promoter, and the percent reduction of exponential growth rate
      mainly caused by gr gene expression was about 20%. The inducibility of the M4
      cell line was greater than that of the R2 cell line because in the M4 cell line
      MMTV promoter controlled gr and lacZ gene expression autoinducibly. Maximum
      induction of the M4 cell line occurred after induction with the hormone
      dexamethasone (Dex) at 10(-7) M, and the final beta-galactosidase content
      increased 400-fold after induction. The optimum conditions for inducer
      concentration and induction time were determined, and the highest production of
      beta-galactosidase occurred when Dex was added after the cell concentration had
      reached its maximum in batch culture. Dex (10(-9) M) is a critical inducer
      concentration in view of inducibility between M4 and R2 cell lines. The
      inducibility of R2 cell line is higher than that of the M4 cell line from 0 to
      10(-9) M Dex, but the inducibility of M4 was higher than that of the R2 cell line
      at Dex concentrations of more than 10(-9) M.

PMID- 8857194
TI  - Influence of aeration on cytoplasmic pH of yeast in an NMR airlift bioreactor.
AB  - Nuclear magnetic resonance spectroscopy has been increasingly pursued as a tool
      for noninvasive, real-time studies of metabolic processes of cell suspension in
      bioreactors. One acute challenge in NMR bioreactor design has been supplying
      enough oxygen for cell respiration in a suspension that contains sufficient cells
      for NMR signal detection. The use of cytoplasmic pH as an intracellular marker of
      adequate oxygenation was evaluated from 31P NMR spectra of the yeast
      Saccharomyces cerevisiae at several cell densities, ranging from low (0.9% (v/v))
      to very high (45% (v/v)) cell densities, in an airlift bioreactor. 31P NMR
      spectra were obtained for derepressed yeast cells prior to, and during,
      glycolysis under nongrowth conditions. During endogenous respiration, pHcyt can
      be used as an intracellular marker for aeration for cell densities up to 18%
      (v/v) based on two criteria: a value of pHcyt at least 0.2 pH units higher under
      aerobic than anaerobic conditions and an absolute pHcyt value of 7.1-7.2. These
      results were more conservative than values of the maximum cell density obtained
      from calculations using kLa and respiration rate estimates and highlight the
      utility of intracellular measurements in conjunction with engineering design
      calculations. During glycolysis, pHcyt values were similar under aerobic and
      anaerobic conditions and hence pHcyt cannot be used as a marker under these
      conditions. Carbon dioxide in the influent gas was observed to aid cells in
      maintaining physiological pHcyt at high cell densities.

PMID- 8857195
TI  - Application of antibody and fluorophore-derivatized liposomes to heterogeneous
      immunoassays for d-dimer.
AB  - Small unilamellar liposomes comprised of cholesterol and phospholipids, in which
      one of the lipids is labeled with a fluorophore, have been covalently
      functionalized with antibodies. The liposomes were conjugated with thousands of
      fluorescein molecules and 10-20 monoclonal antibodies per liposome. These
      bifunctional liposomes were used in a direct (sandwich-type) immunoassay for the
      detection of thromboembolic disorders by assaying for d-dimer. D-dimer is the
      final and the smallest proteolytic product in the degradation of cross-linked
      fibrin by the plasma protein plasmin. The immunoassay using liposomes was
      compared to a conventional immunoassay that uses a fluor-antibody conjugate. The
      liposomes, by virtue of having thousands of fluorophores coupled to one liposome
      in contrast to one or a few reporter molecules in the conventional fluor-antibody
      conjugate, performed better on two counts: (1) they lowered the detection limit
      by a factor of 120 and (2) they provided a 1 order of magnitude amplification in
      signal. The minimum detectable concentration (MDC) of d-dimer was 5.6 ng/mL with
      the liposomal assay as compared to an MDC of 674 ng/mL with conventional fluor
      antibody conjugate. The results of fluorescence assays were also compared with
      the results obtained by Singh et al. (Biotechnol. Prog. 1995, 11, 333-341) in an
      enzyme immunoassay developed using liposomes. These results demonstrate the
      potential of liposomes in lowering detection limits and increasing the
      sensitivity of immunoassays.

PMID- 8857196
TI  - Health interview surveys. Towards international harmonization of methods and
      instruments.
AB  - With the strategy for health for all and its 38 targets, the WHO Regional Office
      for Europe has created a common health policy for Europe, and has developed
      internationally agreed indicators for measuring progress towards the attainment
      of the targets. Some of these indicators are "classical" health indicators, such
      as mortality rates and the incidence of notifiable diseases, while others reflect
      more recent public health concerns such as health-related behaviour and quality
      of life. For the latter group, gathering the information necessary for monitoring
      and evaluating progress is somewhat haphazard. Health interview surveys provide
      the best -- in some cases the only -- means of collecting data on many of these
      indicators, since they mirror the information that only properly approached
      individuals may be able to provide and ensure that all subgroups of the
      population are covered. Yet such surveys have enjoyed a long tradition only in a
      few countries. Moreover, when these indicators are covered, the results are often
      not comparable. The methods and instruments used to collect data have often been
      developed without international coordination or adapted from those used in other
      countries, usually with substantial modification to suit what are perceived to be
      local requirements. There has also tended to be considerable uncertainty among
      those countries lacking a tradition of health interviewing as to the best way of
      conducting surveys. Against this background, the WHO Regional Office and
      Statistics Netherlands organized a series of consultations, which have resulted
      in the internationally agreed methods and instruments for health interview
      surveys set out in this book. These methods and instruments are likely in the
      longer term to become standards, thus improving comparability of information.
      This book provides practical guidance on methods for health interview surveys. It
      is thus essential reading for all concerned in the planning and carrying out of
      such surveys, whether in national statistical offices or in public or private
      interviewing agencies. It will also be useful to all in the public health
      community, including students and academics.

PMID- 8857197
TI  - Acute otitis media.

PMID- 8857198
TI  - Violence.
AB  - Violence affects children and adolescents widely. Pediatricians see many of these
      effects and need to be prepared to address them. A key role for providers in
      addressing violence, however, lies in working to prevent it. In this endeavor,
      the provider must be knowledgeable about the risk factors and vigilant for
      discerning these risks during office visits. Family factors, peer group issues,
      other risky behaviors, and weapons availability and use all are within the range
      of topics that a provider might choose to address. At the same time,
      pediatricians have a key role to play as advocates for children in working with
      community partners to increase supports for children and families, to institute
      new programs to prevent violence, and to help remove firearms from the hands of
      children and youth.

PMID- 8857199
TI  - The pediatrician's role in caring for the developmentally disabled child.

PMID- 8857200
TI  - Gastroesophageal reflux in infants and children who have neurodevelopmental
      disabilities.

PMID- 8857202
TI  - Index of suspicion. Case 1. Diagnosis: erythema infectiosum (EI).

PMID- 8857201
TI  - Ambiguous genitalia.
AB  - The newborn whose genitalia are ambiguous presents a challenge to the
      pediatrician and the family. A clear understanding of the basis of sex
      differentiation and timely consultation with a pediatric endocrinologist is
      critical in the evaluation and determination of sex of rearing in a newborn who
      has ambiguous genitalia. Sex karyotype and a 17-OHP level may suffice in the
      initial evaluation of female pseudohermaphroditism because most patients will
      have virilizing CAH. If male pseudohermaphroditism is suspected on the basis of
      palpable gonads, we routinely obtain a karyotype, basal adrenal steroid levels,
      and levels of hCG-stimulated serum testosterone and DHT, then consider a
      testosterone treatment trial. Physicians who care for children who have ambiguous
      genitalia must appreciate the family's cultural, religious, and psychological
      needs and avoid determining sex of rearing before accurate diagnosis is reached.

PMID- 8857203
TI  - Peptide secondary structure mimetics: applications to vaccines and
      pharmaceuticals.
AB  - An important goal of structural biochemistry is the reduction of complex
      molecules to small functional units that are amenable to high-resolution
      structural analysis and rapid modification. The dissection of multidomain
      proteins into small synthetic conformationally restricted components is an
      important step in the design of low molecular weight nonpeptides that mimic the
      activity of the native protein. Mimetics of critical functional domains might
      possess beneficial properties in comparison to the intact proteinaceous species
      with regard to specificity and therapeutic potential, and are valuable probes for
      the study of molecular recognition events, and the development of novel vaccines
      and pharmaceuticals.

PMID- 8857204
TI  - Perspectives in receptor research.

PMID- 8857205
TI  - Differential eudismic ratios in the antagonism of human platelet function by
      phenoxy- and thiophenoxyacetic acids.
AB  - The antilipidemic drug clofibric acid (CPIB) exhibits antiplatelet effects. In
      order to examine the role of enantioselectivity and hydrophobicity, the
      mono(desmethyl) enantiomers of 2-(4-chlorophenoxy)propanoic acid (CPPA), related
      butanoate homologs, 2-(4-chlorophenoxy)butanoic acid (CPBA), thioether relatives,
      2-(4-chlorothiophenoxy)propanoic acid (CTPA) and corresponding butanoate
      homologs, 2-(4-chlorothiophenoxy)butanoic acid (CTBA) were studied. All compounds
      inhibit prostaglandin-dependent human platelet aggregation and serotonin
      secretion induced by ADP. For the phenoxy acid series, (+)-(R)-CPPA is 5-fold
      more potent than either (-)-(S)-CPPA or CPIB giving a rank order potency of (+)
      (R)-CPPA > (+)-(R)-CPBA > (-)-(S)-CPPA > (-)-(S)-CPBA. With the exception of (-)
      (S)-CTPA, all thiophenoxy acid enantiomers are less potent than their respective
      phenoxy acid isomers [(+)-(R)-CTPA > (-)-(S)-CTPA > (+)-(R)-CTBA > (-)-(S)-CTBA].
      The same rank order of potencies are observed against responses induced by
      arachidonic acid (AA) with the exception of CPIB which is inactive. However,
      inhibition of thrombin-induced [3H]-AA release by phenoxyacetic acids is not
      stereoselective but correlates with hydrophobicity.

PMID- 8857206
TI  - A comparative evaluation of three detectors in the HPLC analysis of sodium
      fusidate.
AB  - A reversed phase liquid chromatographic (HPLC) method is proposed for the
      determination of sodium fusidate, a steroid antibiotic, in a commercial ointment
      using three different detectors: a) fluorescence detector, after a preliminary
      derivatization with 2-bromoacetyl-6-methoxynaphthalene (Br-AMN), b) UV detection
      and c) evaporative light scattering detector (ELSD). Fluorescent derivatization
      was applied directly to the diluted sample, without any purification, whilst UV
      and ELSD detectors involved a preliminary liquid-liquid extraction procedure to
      obtain accurate analysis data.

PMID- 8857208
TI  - Synthesis and antitumor activity evaluation of Delta2-1,2,4-oxadiazoline
      derivatives.
AB  - 4-Adamantyl-5-aryl-3-phenyl-Delta2-1,2,4-oxadiazolines were synthesized and
      evaluated in vitro as antitumor agents against 60 human tumor cell lines. Some
      derivatives exhibit both cell selectivity and tumor growth inhibition activity.
      In particular, 2,6-dichlorophenyl derivative (2q), the most active of the series,
      possesses significant activity on 26 cell lines at 10(-5) M.

PMID- 8857207
TI  - Synthesis of 6,6-dicarboxy-3,4-methano-L-proline, a new constrained glutamate
      analog endowed with neuroprotective properties.
AB  - 6,6-Dicarboxy-3,4-methano-L-proline (L-DCMP, 7) has been prepared by the
      rhodium(II)acetate dimer catalyzed decomposition of dimethyl diazomalonate in the
      presence of a 3,4-didehydroproline derivative. When evaluated against NMDA- and
      kainate-induced toxicity in cultured cortical neurons, L-DCMP (7) exhibited good
      neuroprotective activity.

PMID- 8857209
TI  - 1,2,3-triazolo[1.5-a]quinazolines: synthesis, benzodiazepine receptor binding and
      theoretical calculations.
AB  - This paper reports the synthesis of 3-substituted-1,2,3-triazolo[1,5-a]quinazolin
      5-ones prepared by 1,3-dipolar cycloaddition reaction of 2-azidobenzoic acid to
      methylenic compounds activated by a cyano group. The new derivatives were
      submitted to benzodiazepine receptor binding assays: the results indicated an
      interesting receptorial affinity of the 1,2,3-triazolo[1,5-a]quinazoline ring. On
      the basis of the biological results, theoretical calculations were performed,
      which suggested useful structural modifications.

PMID- 8857210
TI  - Synthesis and pharmacological profile of novel N-substituted N-[5H
      [1]benzopyrano[4,3-d]pyrimidin-2-YL]-N-methylglycinamides.
AB  - The title compounds were synthesized by cyclizing 3-dimethylaminomethylene-4
      chromanone with creatine to give the acid 2 that was successively converted into
      the corresponding amides 3a-f via diphenylphosphorylazide and the relevant
      amines. The free acid 2 and some of 3a-f showed antiinflammatory, hypotensive and
      antiarrhythmic properties.

PMID- 8857211
TI  - Synthesis and antiinflammatory activity of some imidazolinylpyrazole derivatives.
AB  - Some new imidazolinyl-pyrazoles (4) were synthesized by condensation of 2
      imidazolylhydrazine hydroiodid (1a) with beta-ketoesters to afford the
      intermediate 3 that, as free base, ring closes only to 4. The attempt to obtain
      the imidazo-triazepinone 5, starting from 2-imidazolinyl-2-methylhydrazine, was
      accomplished, in low yield, only in reacting with ethyl acetoacetate. The
      pharmacological evaluation of antiinflammatory and analgesic activities of
      pyrazoles 4a-f revealed an appreciable antiinflammatory activity.

PMID- 8857212
TI  - Gulf war syndrome and vasodilation.

PMID- 8857213
TI  - Tobacco sales--intrusion is justified.

PMID- 8857214
TI  - Tobacco sales should stop.

PMID- 8857215
TI  - Parachuting injuries: a medical analysis of an airborne operation.
AB  - The purpose of this paper is to discuss parachuting variables as they affect
      support and planning. The authors retrospectively analyzed an operation in which
      a Ranger battalion parachuted onto an airfield drop zone. Leaders weighed Rangers
      to estimate the soldiers' load. The advance team failed to adequately coordinate
      administrative medical assistance on the drop zone. Forty-one Rangers were
      injured and evacuated from the drop zone (8.6% of the jumpers). Variables in such
      operations include drop zone selection, equipment weight, drop altitude, wind
      speed, the wind-flight angle, drop height, and jumper density over the drop zone.
      Solutions include cargo drops and leaders' repeated emphasis on minimizing the
      soldiers' loads in accordance with mission accomplishment.

PMID- 8857216
TI  - Health risk appraisal and serum cholesterol nutrition education: an outcome
      study.
AB  - Records of 59 U.S. Army service members identified as at-risk for coronary heart
      disease were reviewed. Soldiers were divided into groups that completed and did
      not complete cholesterol nutrition education classes. Differences in the means of
      repeated cholesterol measures were compared within each group. Results showed
      statistically significant declines in total cholesterol, with t(35) = 2.94, p <
      0.01 for the class completion group and t(22) = 2.18, p < 0.05 for the dropout
      group. Similar results were noted for low-density lipoprotein measures. However,
      cholesterol differences in the means between the two groups were not
      statistically significant. Results indicate that decreases in serum cholesterol
      may occur due to at-risk reactive behavior, but that full compliance with the
      current nutrition education program does not appear to further reduce cholesterol
      levels to any appreciable degree.

PMID- 8857217
TI  - Ergometry as a predictor of basic military training success.
AB  - One hundred U.S. Air Force recruits were administered the cycle ergometry test to
      determine their aerobic fitness and timed on a 2-mile run before beginning the
      physical conditioning phase of training. The estimated oxygen consumption (vO2)
      was calculated for all trainees completing the ergometry test. The mean estimated
      vO2 for those successfully completing basic military training (BMT) on schedule
      was 27.95 +/- 1.74 ml/kg/minute, whereas the mean estimated vO2 for those not
      completing the program on schedule was 32.94 +/- 3.55 ml/kg/minute (not
      statistically different). For the 2-mile run, the times ranged from 14 minutes 17
      seconds to 29 minutes 11 seconds. The mean run time for those completing BMT on
      schedule was 22 minutes 28.15 seconds +/- 25.79 seconds, compared to 21 minutes
      19.46 seconds +/- 1 minute 26.30 seconds for those not completing the program on
      schedule (not statistically different). Neither relative risk nor chi-square
      calculations were statistically significant. No significant associations between
      run times or a passing cycle ergometry score at the beginning of BMT and
      successful completion of BMT were found.

PMID- 8857218
TI  - Military psychiatry: a cross-cultural perspective.
AB  - Although previous authors have noted that U.S. military personnel share beliefs,
      values, and behaviors defining the military as a separate culture, military
      psychiatry has not previously been presented from a cross-cultural perspective.
      Viewing the military psychiatrist from this perspective reveals new observations
      and explanations for the role he or she plays within that culture, for
      differences in demographic data regarding diagnoses and patient population, and
      for different treatment issues surrounding military patients and their
      dependents. It also has implications for the recruitment, training, and retention
      of military psychiatrists. Learning to navigate within the minority culture of
      the military and to act as a liaison between that culture and the dominant one
      serves to broaden the skills of the military psychiatrist.

PMID- 8857219
TI  - A comprehensive weight-loss program for soldiers.
AB  - A weight-loss treatment program for active duty military personnel is discussed
      and evaluated. The Fat Loss and Exercise Program at U.S. Army Hospital,
      Bremerhaven, Germany, consisted of a 3-week inpatient treatment program and 6
      months of weekly outpatient follow-up. The program combined a multidisciplinary
      team approach to the treatment of obesity--psychology, internal medicine,
      nursing, nutrition care, and physical therapy. Patients showed a significant
      weight and body fat loss [F(2,90) = 52.91 and 65.85, p < 0.001, respectively]
      from the initiation of treatment (mean = 205.9 pounds, 28.91%) to the end of the
      inpatient program (mean = 192.8 pounds, 25.97%) with maintenance over 6 months
      (mean = 190.4 pounds, 25.03%). Changes in cholesterol levels by treatment phase
      are also discussed. Results demonstrate positive increases in high-density
      lipoprotein at each phase. These results support a comprehensive,
      multidisciplinary inpatient treatment of obesity within the military.

PMID- 8857220
TI  - A prospective study of the application of transfusions in a field hospital during
      the war in Croatia.
AB  - Use of blood products are recommended worldwide as a substitution for whole
      blood. In the case of war wounds, because of their specificity, this is not
      possible. We studied prospectively the use of blood and blood products during
      management of the wounded in a field hospital during the war in Croatia. During a
      6-month period, 178 soldiers out of a total number of 593 were hospitalized, and
      of this number 64 (36%) received transfusions. Localization of the wound, and
      speed and quality of first aid had significant effects on the average amount of
      blood used. Consequently, norms for blood use in wartime in west European
      countries and NATO are lower than what we used for each wounded patient. Ensuring
      an adequate amount of whole blood still remains one of the primary tasks of the
      transfusion service in wartime.

PMID- 8857221
TI  - A proposal for improving the acquisition of medical data in forward field
      hospitals.
AB  - Current medical recording policy in forward field hospitals adequately delineates
      battle and non-battle injuries and incapacitation from sickness or disease.
      Although useful for planning, such data do not often provide insights that could
      improve medical care. The author has gathered combat medical data in Vietnam and
      Desert Storm and concludes that by providing and storing carbon copies of
      admission and operating room logs plus operative notes, discharge summaries, and
      the clinical record cover sheet, the Army Medical Corps would have a permanent,
      analyzable account of field hospital medical activities. Digital copying and disk
      storage of these specific documents would greatly increase their usefulness,
      especially if coupled with standard data formats for admission and operating logs
      and a simple diagnosis coding scheme to aid data retrieval either by hand or
      computer. Medical data should be made available to concerned forward medical
      personnel because in past wars some of the most insightful medical observations
      of immediate help to the sick and wounded have been made by individual physicians
      analyzing medical data at the front.

PMID- 8857222
TI  - Suicide prevention in an army infantry division: a multi-disciplinary program.
AB  - This article is intended to provide an overview of the 25th Infantry Division
      (Light) Suicide Prevention Program. A multidisciplinary intervention model, it
      outlines the role of chaplains and division mental health officers as well as
      indicators or warning signs relevant to army personnel who have committed
      suicide. Prevention strategies applicable to the military community, including
      Crisis Intervention Command Consultations, will be recommended. It is hoped that
      this information will not only assist professionals in identifying personnel at
      risk for suicide, but aid in the development of other suicide prevention
      programs.

PMID- 8857223
TI  - Graduate medical education in the Department of Defense.
AB  - The Department of Defense supports over 3,000 physician trainees in graduate
      medical education (GME) programs in military hospitals located throughout the
      United States. The number of trainees has been gradually declining over the past
      5 years because of budget constraints and the personnel draw-down in the military
      that are results of the end of the Cold War. The Department of Defense has
      developed a GME strategy for determining the proper size of its GME programs. The
      tenets of the GME strategy include closing GME programs that do not fill trainee
      positions and that are not of the highest quality in accordance with
      Accreditation Council for Graduate Medical Education standards, ensuring that the
      number of GME trainees does not exceed one-quarter of the total number of the
      active duty physicians in the Department of Defense, and minimizing the number of
      civilian trainees in military hospital GME programs.

PMID- 8857224
TI  - Osteoarthritis of the knee among Saudi Arabian security forces personnel.
AB  - The prevalence and pattern of osteoarthritis of the knee and its association with
      obesity among security forces personnel was investigated. A single survey with a
      control group was done at the Mobile Hospital, Ministry of Interior, Makkah Al
      Mukarramah. One hundred twenty-five patients presenting to the orthopedic clinic
      with painful knees of at least 12 months duration gave detailed histories and
      were treated with bi-planar conventional radiography; they were matched with a
      similar number from the clinics of internal medicine without painful knees. One
      hundred three patients (82.4%) with 126 painful knees had various degrees of
      osteoarthritis. The mean age was 41 and 41.76 years for the patient and control
      group, respectively. The medial tibio-femoral and patello-femoral compartment
      were involved in 116 cases (92%). Fifty-nine knees (46.8%) had mild, 46 (36.5%)
      had moderate, and 21 (16.6%) had severe osteoarthritis changes. There were
      statistically significant differences between the two groups for weight and
      Quetelet index of body mass (p < 0.047 and < 0.0001). In the study group, the
      mean Quetelet body index was 31.6638 kg/m2, and in the control group it was
      28.5633 kg/m2. The prevalence of osteoarthritis among the security forces
      personnel was 1.19%. The medial and patello-femoral compartment was affected in
      the majority of cases, and obesity was confirmed as one of the important causes
      of osteoarthritis in the Saudi Arabian population.

PMID- 8857225
TI  - Delayed diagnosis of large cerebello-pontine angle tumors, despite hearing
      conservation training.
AB  - Recently, at the National Naval Medical Center in Bethesda, Maryland, we have
      encountered several patients with large cerebello-pontine angle tumors. All were
      active duty and had evaded the military's stringent hearing screening program
      until the tumors were of life-threatening size. Early detection of these tumors
      can reduce overall morbidity and improve the patient's chances of returning to a
      normal lifestyle. We have analyzed each of these cases and discovered weaknesses
      in the program. The primary difficulty was in accurately following the algorithms
      set forth by military regulations. To that end we recommend: (1) establishing a
      cutoff for identification of those who should be evaluated after they obtain
      their enlistment/annual physical examinations; (2) specific training for hearing
      conservation program managers in the algorithms for hearing screening; (3)
      establishment of specific guidelines for primary care physicians for further
      evaluation of abnormal audiograms; and (4) reevaluation of form DD 2216.

PMID- 8857226
TI  - Perception and use of insect repellent among soldiers in the Singapore Armed
      Forces.
AB  - The Singapore Armed Forces currently uses the 75% DEET formulation insect
      repellent. To study the perception, use, and acceptability of this insect
      repellent, a survey was carried out on servicemen who had participated in field
      exercises. Although over 80% of the servicemen knew the proper use of the insect
      repellent and brought along the army-issued repellent in the field, less than
      half used this repellent frequently while on exercise. Eighty-three percent felt
      that the army repellent was only effective sometimes and that it lasted for 4
      hours or less. Skin irritation was a common side effect when using the repellent.
      About 70.4% had used commercial insect repellents and perceived them to be more
      long lasting and with fewer side effects. The results from our study indicate
      that the army-issued insect repellent currently used is not totally acceptable to
      our servicemen. Thus, there is a pressing need to develop or acquire a better
      insect repellent that is more or just as effective, has fewer side effects in
      terms of smell and skin irritation, and with an improved mode of delivery, such
      as aerosol or pump spray.

PMID- 8857227
TI  - The U.S. Army HIV testing program: the first decade.
AB  - In response to the human immunodeficiency virus (HIV) epidemic, the U.S. military
      established comprehensive policies to protect individual and public health and to
      assure military readiness. Central to this effort was the creation of a total
      force HIV screening program. As representative of these military programs, the
      U.S. Army's HIV testing program is described. The first decade of this program is
      assessed from financial, research, policy, and epidemic-control perspectives. We
      conclude that the government's investment has been a prudent one, leaving the
      U.S. military better positioned to counter the threats posed by the HIV pandemic.

PMID- 8857228
TI  - Prevention and treatment of HIV infections in minorities in the US military: a
      review of military research.
AB  - The prevalence and incidence of HIV-1 infection in the U.S. military has been
      higher in minorities than in whites. In order to understand the reason for this
      disproportionate impact of the epidemic, military HIV research efforts were
      reviewed for race/ethnic-specific differences in a conference held in July 1993.
      Studies presented were from the areas of epidemiology, natural history,
      treatment, and prevention. This report summarizes the presentations made at that
      conference. Few race/ethnic-related differences were identified in this setting
      of early diagnosis of HIV-1 infection and equal access to a quality health care
      system. More information of this type will be needed to allow the targeting of
      interventions for maximal effect in decreasing the risk of HIV infection.

PMID- 8857229
TI  - A case of tungiasis.
AB  - Tunga penetrans is a burrowing flea that is prevalent in Central and South
      America, the Caribbean, tropical Africa, India, and Pakistan, and rarely is
      imported to the United States. Tungiasis results from the cutaneous infestation
      of humans by the gravid female flea, T. penetrans. We report a case of tungiasis
      in a female who had been on a missionary expedition along the Brazilian Amazon
      River. The clinical presentation, life cycle, differential diagnosis, military
      and historical aspects, and treatment are discussed.

PMID- 8857230
TI  - Surgery for hydatid cysts of the liver.
AB  - This report details the perioperative management of 488 patients who underwent
      surgery for hydatid cysts of the liver. The most common pathology was a single
      cyst in the right lobe of the liver (53%). The preferred surgical procedures were
      partial cystectomy with closure of the residual cavity by suturing (31%) and
      total cystectomy (18%). Communication with the biliary system was found in 13% of
      cysts. The presence of multiple cysts and the need for additional procedures
      contributed to the overall perioperative morbidity (42%) and mortality (1%).

PMID- 8857231
TI  - A mapping of histology and cell proliferation in human bladder cancer: an
      immunohistochemical study.
AB  - Transitional cell carcinoma of the urinary bladder is a multifocal disease and
      the whole bladder mucosa is more or less involved in the neoplastic process. A
      mapping study of 5 cystectomy specimens was performed, and cell proliferation was
      evaluated immunohistochemically using anti-proliferating cell nuclear antigen
      (PCNA) monoclonal antibody. A correlation between the pathological findings and
      the rates of PCNA-positive cells was observed in both the tumor and the
      surrounding mucosa in 4 of the 5 cases. The rates of PCNA-positive cells
      increased in areas with normal mucosa adjacent to those with dysplasia or
      transitional cell carcinoma, and in areas with normal mucosa or dysplasia
      adjacent to those with carcinoma in situ or transitional cell carcinoma in 2
      cases. These features may indicate that a field change observed in the mapping
      study of a bladder with cancer is a manifestation of a stepwise progression of
      the mucosal disease.

PMID- 8857232
TI  - Clinical evaluation of human granulocyte colony-stimulating factor in
      chemotherapy for ovarian cancer.
AB  - The clinical evaluation of human granulocyte colony-stimulating factor (G-CSF) in
      38 patients treated with chemotherapy for ovarian cancer stage III was
      investigated among 3 groups. G-CSF was not given in group A (19 courses), was
      administered from day 5 of chemotherapy in group B (53 courses), and was given
      when the WBC count decreased to below 2,000/mm3 in group C (29 courses). The time
      to nadir was significantly shorter in group B compared with groups A and C and
      revealed 10 days for the WBC count and 11 days for the neutrophil count (p
      <0.01), with mean nadir values of 2,896/mm3 and 982/mm3 respectively, and so the
      count of WBC and neutrophil have been kept during the course. The effect of G-CSF
      was not modified by age, body weight or the number of chemotherapy courses in
      groups B and C. These results demonstrate that early treatment with G-CSF may
      allow increased intensity of chemotherapy by using greater doses or by shortening
      of the interval between cycles.

PMID- 8857233
TI  - Cytology and microenvironment of somatostatin (D) cells in the gastric fundic
      mucosa of rodents.
AB  - Somatostatin from gastric D-cells exerts an inhibitory effect upon the release of
      gastric acid, enzymes and gastrin. From previous investigations, a paracrine mode
      of action of somatostatin has been postulated. However, the exact route of the
      delivery of gastric somatostatin remains still uncertain and controversial. To
      obtain a closer view of fundic D-cells, the complete shapes and their
      microanatomical relationships to neighboring tissue elements were examined in
      immunostained serial semithin (0.5 mu m) sections of the fundic mucosa of rats,
      mice and golden hamsters, exemplarily by the combined utilization of computer
      assisted 3D reconstructions. All the D cells examined in the present study were
      found to belong to the 'closed-type' of entero-endocrine cells lacking contiguity
      to the luminal surface. In their shape, the D cells in this region displayed an
      expressed 'pleomorphism'. A subpopulation of D cells, ovoid in shape, were
      thoroughly enclosed by single parietal cells. Most of the D cells appeared to be
      intimately juxtaposed to parietal cells and/or chief cells with their cell bodies
      or cytoplasmic processes, but simultaneously blood capillaries were regularly
      located in close vicinity to such D cells. Thus, somatostatin from the fundic D
      cells may act upon parietal cells and chief cells via both paracrine (direct cell
      to cell or diffusion) and endocrine (local circulatory system). The morphological
      heterogeneity of gastric fundic D cells may reflect certain functional states.

PMID- 8857234
TI  - Factors related to the outcome of M-VAC in 101 patients with advanced urothelial
      cancer.
AB  - The objective of this study is to identify factors related to the results of
      intravenous methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for 101
      patients with advanced urothelial cancer. The effects of various factors on
      response and survival were evaluated using univariate and multivariate analyses.
      The factors included in the analyses were sex, age, performance status (PS),
      primary site, histological type, grade, T category, N category, M category, prior
      chemotherapy, prior radiotherapy, and dose of chemotherapeutic drugs. Univariate
      analysis revealed that M category and prior chemotherapy had a significant
      correlation with the response, and that factors significantly related to survival
      were PS, primary site, N category, M category, prior chemotherapy and prior
      radiotherapy. A multiple logistic regression model showed that N category, M
      category and prior chemotherapy were related to response. The response rates of
      patients with N1-4 or M1 or prior chemotherapy were lower than those with N0 or
      M0 or without prior chemotherapy. A Cox regression model demonstrated that PS and
      M category independently contributed to survival. Patients with high grade PS or
      distant metastases showed a lower survival rate than those with low grade PS or
      localized diseases. M category was the most important factor related to response
      and survival. These results seem to indicate the low effectiveness of M-VAC for
      distant metastases, and the inability of this regimen to improve the outcome of
      patients with advanced urothelial cancer.

PMID- 8857235
TI  - The effects of modulation of the L-arginine-nitric oxide pathway on myocardial
      stunning following repetitive coronary occlusion in dogs.
AB  - In order to determine the role of nitric oxide (NO) in myocardial stunning, the
      effects of both augmenting and inhibiting NO production on contractile function,
      following repetitive coronary occlusions, were evaluated in anesthetized dogs.
      The effect of the experimental protocol on endothelial function was also
      assessed. The increases in coronary blood flow in response to acetylcholine and
      nitroglycerin at 30 and 60 min after reperfusion were similar to those before
      coronary occlusions. Therefore, loss in vasodilator reserve was not observed
      following the multiple coronary occlusions used in this study. NG-nitro-L
      arginine methyl ester (L-NAME) elevated blood pressure slightly, but did not
      change left ventricular end-diastolic pressure, left ventricular maximum positive
      dp/dt, and coronary blood flow. Although the degree of systolic bulging and
      collateral circulation during coronary occlusions was comparable to the control
      group, contractile function after reperfusion was significantly worse in the
      presence of L-NAME than in the control. The recovery of contractile function was
      also considerably delayed with administration of L-arginine. This deleterious
      effect on contractile function was not observed with its enantiomer D-arginine.
      Differences in collateral blood flow determined with microspheres and hemodynamic
      variables did not account for the effects of L-arginine. These results suggest
      that endogenous NO is important in limiting myocardial stunning following
      repetitive coronary occlusion. However, NO may be cytotoxic when present in
      substantial excess.

PMID- 8857237
TI  - Lipoprotein(a) in cerebrovascular and coronary atherosclerosis.
AB  - Serum lipoprotein(a) [Lp(a)] was determined in 85 healthy controls (control
      group), in 49 patients with cerebrovascular disease (CVD group), and in 87
      patients with acute myocardial infarction (AMI group). Lp(a) concentration was
      measured using a single radial immunodiffusion method. Because Lp(a) showed a
      skewed distribution, Lp(a) was plotted in each group on a box plot and analyzed
      using non-parametric methods. The following results were obtained: 1) Lp(a)
      levels were significantly higher in both the AMI and CVD groups than in the
      control group. 2) The CVD group was divided into 4 groups: [1] cerebral
      hemorrhage (HEM); [2] cardioembolic infarction (EMB); [3] lacunar infarction
      (LAC); and [4] atherothrombotic infarction (THR). In the THR group, Lp(a)
      concentration was higher than those in the control and LAC groups. 3) In the CVD
      group, patients with an elevated Lp(a) value showed severe lesions in the major
      cerebral arteries evaluated by cerebral arteriograms. 4) In the AMI patients who
      underwent coronary angiography, the Lp(a) level showed a marked increase with an
      increase in the number of affected vessels. The correlation between coronary
      index (CI) and Lp(a) was also investigated. The lesion severity of coronary
      arteries was correlated with serum Lp(a) concentration. These results suggest
      that a high Lp(a) value is linked to atherosclerosis of the cerebral and coronary
      arteries, and influences its severity.

PMID- 8857236
TI  - Cisplatin-based neoadjuvant chemotherapy for invasive bladder cancer.
AB  - Between February 1988 and March 1993, 24 patients with locally advanced bladder
      cancer (stages T2-4N0-3M0) were included in this study. Combination chemotherapy
      consisting of methotrexate, vinblastine, epirubicin (doxorubicin) and cisplatin
      (M-VAC) was given to the patients in a neoadjuvant setting. The clinical stage
      was T2N0M0 in eight patients, T3aN0M0 in three, T3bN0M0 in seven, T4N0M0 in five
      and T4N3M0 in one. After chemotherapy, total cystectomy was performed in 20
      patients and partial cystectomy 4. Of 24 patients, one (4%) showed a pathological
      complete response, and eight (33%) had a pathological partial response, for an
      overall response rate of 38% (95% confidence limits 20 to 57%). Nine patients who
      achieved a pathological response to chemotherapy had a significantly higher
      survival rate than the nonresponders (p <0.01). In the relationship between the
      clinical stage and the response to chemotherapy, clinical T2 and T3a diseases
      were more likely to respond to chemotherapy than clinical T3b and T4 diseases,
      with a response rate of 64% and 15%, respectively. While a positive relationship
      between the pathological response and survival was observed, adequate follow-up
      is needed to assess the ability of neoadjuvant chemotherapy to improve the
      prognosis of patients with locally advanced bladder cancer.

PMID- 8857238
TI  - Intussusception due to inflammatory fibroid polyp of the ileum. A report of two
      cases from Turkiye.
AB  - Intussusception due to inflammatory fibroid polyps is a very rare entity. In this
      article two cases of inflammatory fibroid polyps of the ileum (A 32-year old man
      and a 50-year old woman) in Turkiye are described. Both patients were admitted to
      the hospital because of acute intestinal obstruction as a result of an
      intussusception caused by a polyp. The lesions were characterized by an
      eozinophil containing loosely structured fibrous tissue comprising an onion-skin
      like arrangement of reticular fibers with spindle-shaped nuclei localised in the
      submucosa and the base of the mucosa, and variable proliferation of fibroblasts
      and small vessels. The aetiology of these polyps remains obscure but they appear
      to be a reactive process (allergic or foreign body reaction) rather than
      neoplastic. Nkanze et al reported 12 cases of intussusception due to fibroid
      polyps in Africa. Our two cases are the first cases in Turkiye.

PMID- 8857240
TI  - A thesis for our times.

PMID- 8857241
TI  - Palliative performance scale (PPS): a new tool.
AB  - The Palliative Performance Scale (PPS), a modification of the Karnofsky
      Performance Scale, is presented as a new tool for measurement of physical status
      in palliative care. Its initial uses in Victoria include communication, analysis
      of home nursing care workload, profiling admissions and discharges to the hospice
      unit, and, possibly, prognostication. We assessed 119 patients at home, of whom
      87 (73%) had a PPS rating between 40% and 70%. Of 213 patients admitted to the
      hospice unit, 175 (83%) were PPS 20%-50% on admission. The average period until
      death for 129 patients who died on the unit was 1.88 days at 10% PPS upon
      admission, 2.62 days at 20%, 6.70 days at 30%, 10.30 days at 40%, 13.87 days at
      50%. Only two patients at 60% or higher died in the unit. The PPS may become a
      basis for comparing drug costs at home and for studying the effects of treatments
      (e.g. hypodermoclysis) at various levels of physical performance. Validity and
      reliability testing are currently being undertaken.

PMID- 8857239
TI  - A case of traumatic pseudoaneurysm of the ascending aorta occurring in a
      postoperative patient who underwent arch replacement and Bentall's operation.
AB  - A case of traumatic pseudoaneurysm of the ascending aorta occurring in a
      postoperative patient who underwent an arch replacement and Bentall's operation
      was reported. A bleeding point was clear at the graft of the ascending aorta, and
      a pseudoaneurysmal formation was suspected following an echocardiogram. An
      aortogram demonstrated the presence of an aneurysm approximately 8 cm by 4 cm in
      size originating 5 cm above the right coronary ostia. An emergency operation was
      carried out. A Trans-femoral bypass was established before sternotomy. The
      Operative findings showed that adhesive connective tissue covered a
      pseudoaneurysm 8 cm by 4 cm in size, and that there was a tear in the anastomosis
      of the grafts between the ascending aorta and the arch 5 cm above the coronary
      ostia. Direct suture was performed, using hypothermic circulatory arrest. In this
      paper, We discuss the mechanism, classification, and operative strategy of
      traumatic pseudoaneurysm.

PMID- 8857242
TI  - Bereavement follow-up: what do palliative support teams actually do?
AB  - Care for the family and bereavement follow-up is considered part of good
      palliative practice. Risk assessment schedules and recommended methods of follow
      up are available but the extent to which these are used in practice is not known.
      This study examines the bereavement follow-up to families and carers by five
      palliative support teams in England, UK. We report the bereavement follow-up
      provided and compare the responses of different teams. Data were collected on all
      patients using standardized records. This included patient and family details and
      the initial bereavement follow-up after the death. A total of 320 patients were
      cared for until death: 55% men, 45% women, mean age 64 years. All patients had
      cancer except one who had AIDS. Civil status was 64% married, 20% widowed, 5%
      divorced or separated, 9% single, and 2% other. 49% lived with one other person,
      19% alone, and the remainder with two or more people. Spouses were the most
      significant carers at 62%. Bereavement follow-up was offered to 215 or 67% of
      families, but this varied greatly between the teams (10%-94%). Initial follow-up
      was made mainly by the nurses (78%). 50% of follow-ups were by visits, 45% by
      telephone contact, 3% by letter, and 1% other. Reasons for no follow-up included
      (a) no relatives 12%, (b) staff did not know the family well enough 29%, (c)
      carers lived outside the visiting area of the team 25%, (d) carers were judged as
      having no need 23%, (e) carers refused 1%, (e) other 4%, and (f) not recorded 5%.
      The results indicate the diversity of bereavement follow-up and suggest a need
      for training, clear protocols, and further research into the needs of families.

PMID- 8857243
TI  - A reliability and validity study of the McMaster Quality of Life Scale (MQLS) for
      a palliative population.
AB  - The McMaster Quality of Life Scale (MQLS) was developed to measure the quality of
      life in a palliative patient population. This paper describes the tool and its
      psychometric properties. Palliative stage patients could assess their condition
      using this tool (r = 0.84; 95% Cl 0.76-0.94). Although ratings by different
      raters (patient, family, staff) were correlated, systematic differences were
      found by source of rating, which suggests that proxy rating (substituting family
      or staff ratings for a patient rating) should be avoided. The MQLS was sensitive
      to changes in the patient's quality of life. Neither age nor sex of patient
      influenced total score obtained. Persons close to death rated their quality of
      life as being poorer than those who were alive at the end of the data collection
      period. People who needed to have the MQLS read to them rated their quality of
      life somewhat lower than patients who could complete the task by themselves.
      Staff-rated MQLS scores correlated significantly with the staff-rated Spitzer
      Quality of Life Index. This study suggests the MQLS is a reliable and valid
      measure of quality of life during the palliative phase.

PMID- 8857244
TI  - Life expectancy in hospitalized patients with AIDS: prognostic factors on
      admission.
AB  - In the course of the inevitable hospitalizations of AIDS patients, many difficult
      questions concerning curative and palliative approaches to care have to be
      answered. In order to guide these strategies, we conducted a prospective study to
      identify those variables which can be easily quantified on admission which might
      be predictive of patient outcomes. Between 1 June 1990 and 25 April 1991, 140
      consecutive hospitalizations of 83 AIDS patients were recorded. Demographic,
      clinical, and biological data were collected within 48 hours of admission.
      Probable (p <0.10) or definite (p <0.05) factors contributing to a higher
      mortality included type of opportunistic infections, serum albumin level, total
      lymphocyte count, weight, CD4 cell count, and neurological manifestations. In the
      multivariate proportional hazards model, two factors were significantly and
      independently predictive of lower survival: body weight less than 90% of ideal
      body weight and neurologic manifestations. The probability of survival was
      significantly affected by the number of predictive factors present on admission,
      and patients were significantly more likely to die when these latter two factors
      were present concomitantly. These factors might be useful to define the optimal
      mode of care for hospitalized AIDS patients, considering both patients' wishes
      and an objective assessment of the prognosis.

PMID- 8857245
TI  - Funeral rituals following the death of a child in Taiwan.
AB  - This study explores the practices of 25 Taiwanese families following the death of
      a child from cancer. Detailed description of the families' post-death practices
      was obtained through semi-structured interviews with at least one family member.
      Through content analysis of the data, 10 categories were identified. These were:
      caring for the body, funeral arrangements, mourning clothes, ashes, spirit
      tablets, child's belongings, child's room, visits to the grave or the temple,
      dreams, and talking about the dead child. The findings show that although the
      rituals performed following the death of a child are simpler than those
      traditionally performed for an adult, they are still an important part of the
      families' lives during the post-death period.

PMID- 8857246
TI  - Platelet transfusions in advanced hematological malignancies: a position paper.
AB  - Treatment of patients with advanced-stage hematological malignancies (HM)
      includes frequent transfusions. Given present limited hospital budgets,
      administrative pressure is increasing on hematology services to limit the cost of
      these transfusions. An expert multidisciplinary panel involved in hematology
      formed a working party to draw up a series of proposals, including definitions of
      advanced stage disease and the indications for platelet transfusion. Their
      proposals included: (a) Platelet transfusions are indicated for the treatment of
      bleeding caused by low platelet counts; (b) Patients should receive full
      information, including the basic criteria for platelet transfusion; (c) Doctors
      should be trained to assess whether or not platelet transfusions are urgently
      required; and (d) The practice of home transfusions should be encouraged.

PMID- 8857247
TI  - A circular diagram for representing symptom status in advanced cancer patients.
AB  - Symptom relief is the major goal of palliative care. Its assessment is essential
      and several methods have been described. To evaluate immediately the clinical
      situation, a circular diagram for a visual representation of the physical
      symptoms is proposed. Particular patterns derived from the given data emerge from
      the diagrams. Certain critical situations often observed in palliative care,
      especially in the last weeks of life, show specific patterns that are easily
      distinguished. Effective treatments may change the appearance of different
      pictures.

PMID- 8857248
TI  - Symptomatic hypocalcemia after intravenous pamidronate.
AB  - A 65-year-old woman admitted for palliative care of metastatic renal/bladder
      carcinoma developed symptomatic hypocalcemia nine days following a single dose of
      pamidronate. This may have implications for management of patients following
      discharge from hospital.

PMID- 8857249
TI  - How should we use transdermal fentanyl (TF) for pain management in palliative
      care patients?

PMID- 8857250
TI  - Clinical application of chemiluminescent immunoassay for thyroid stimulating
      hormone, free-T4 and intact-parathyroid hormone.
AB  - To meet the demands of clinical practice, rapid, sensitive and specific
      laboratory tests are essential. We evaluated the performance of a newer
      generation of chemiluminescent immunoassay (CLIA) system (Immulite, Diagnostic
      Products Corp, Los Angeles, CA, USA) and compared it with a popular
      immunoradiometric immunoassay (IRMA) system. The data of 158 patients whose
      thyroid function was assessed and that of another 158 patients whose parathyroid
      function was assessed were analyzed. The thyroid stimulating hormone (TSH) CLIA
      is an ultrasensitive TSH (us-TSH) assay that provides more detailed, reliable
      results for low TSH concentrations than TSH IRMA. Coupled with the free-T4 assay,
      the us-TSH assay enhances the ability to detect and monitor the status of thyroid
      dysfunction. Intact-parathyroid hormone (PTH) CLIA can detect lower serum intact
      PTH levels, is more sensitive and is as reliable as IRMA. Combined with serum
      calcium levels and clinical conditions, it proved efficient and discriminated
      reliably between hypercalcemia associated with malignancy and that of
      hyperparathyroidism.

PMID- 8857251
TI  - Preimplantation diagnosis of alpha-thalassemia by blastomere aspiration and
      polymerase chain reaction: preliminary experience.
AB  - The ability to diagnose and detect the presence of debilitating and life
      threatening diseases would be an invaluable asset to those involved in in vitro
      fertilization programs. To investigate the possibility of diagnosing severe alpha
      thalassemia before implantation, DNA sequences targeting the abnormal deletion
      breakpoint and the normal region of the alpha-globin gene were amplified by
      polymerase chain reaction from blastomeres aspirated from human preimplantation
      embryos. Before performing this experiment, a mouse model blastomere aspiration
      technique was examined to confirm embryo survival and normal development
      capability. The mouse embryos showed undisturbed development in the five- to
      seven-, as well as the eight-cell stages when one, or two (eight-cell stage only)
      blastomeres were aspirated. The four-cell embryos had a lower survival rate but
      had a blastocyst formation rate comparable to the more advanced stages and the
      control embryos. In the human embryo experiment, no homozygous Southeast Asian
      alpha-thalassemia was detected in the aspirated blastomeres, although two
      heterozygotic alpha-thalassemia embryos were discovered. The sensitivities of
      targeting sequence detection in the mouse and human blastomeres were between 50%
      and 76% in the respective groups. This study supports the feasibility of
      preimplantation diagnosis of severe alpha-thalassemia when both father and mother
      are carriers of this inheritable disease.

PMID- 8857252
TI  - Neurologic complications of pediatric systemic malignancies.
AB  - From 1991 to 1995, we reviewed the medical records of 200 pediatric patients with
      systemic malignancies to study the occurrence of neurologic complications and
      their treatment. A total of 25 patients with neurologic complications were found.
      Complications included intracranial metastasis (one patient), intraspinal
      metastasis (one), spinal epidural compressions (three), leptomeningeal metastases
      (six), metabolic encephalopathy (10), opportunistic infection (one),
      cerebrovascular disorders (three), treatment complications (six) and
      paraneoplastic syndromes (two). Ten patients had seizures. One patient with acute
      lymphoblastic leukemia (ALL) had the unusual complication of cytomegalovirus
      retinitis and glaucoma. Seven patients had neurologic features at presentation.
      ALL was the most common malignancy (56%) and neuroblastoma (20%) was the second.
      Neurologic deficits are frequently seen in pediatric patients with systemic
      malignancies and can, in fact, be the presenting signs. Early diagnosis and
      treatment is important to prevent further neurologic disability.

PMID- 8857253
TI  - Bronchial foreign bodies in adults.
AB  - Aspiration of foreign bodies into the bronchial tree is infrequently seen in
      adults. We reviewed 40 such cases during an 8-year period at Chang Gung Memorial
      Hospital, Kaohsiung. Only six patients had underlying conditions that contributed
      to the aspiration of foreign bodies. A positive history of aspiration was found
      in 18 patients (48%). Clinical manifestations were nonspecific. Chest
      roentgenograms were useful in 11 of the 40 patients. Bronchoscopic findings were
      classified into three groups: foreign bodies in the bronchial tree without
      granulation tissue, foreign bodies in the bronchial tree with marked granulation
      tissue and foreign bodies embedded in the granulation tissue. The diagnoses and
      removal of foreign bodies were successful in 37 patients (92%) using grasping
      forceps or biopsy forceps and in one patient using basket type grasping forceps.
      Complications of bronchoscopy were rare and not serious. The diagnosis of occult
      foreign bodies is often difficult and demands a high index of suspicion. Removal
      of endobronchial foreign bodies is usually possible with a flexible fiberoptic
      bronchoscope and has a high success rate.

PMID- 8857254
TI  - Neonatal endotracheal tube leakage and compliance and resistance measurements.
AB  - The effects of neonatal endotracheal tube (ETT) leakage on inspiratory compliance
      (Ci) and resistance (Ri) were examined using a lung model with constant
      compliance. An air leak was created at the end of an ETT. Flow was measured at,
      above and below the leak by a hot wire anemometer and a pneumotach. Tidal volume
      (VT) was derived from digitally integrated flow. Pressure was measured at the
      side port of the ETT adaptors above and below the leak. Percent of air leak (%
      leak) was defined as the difference between inspiratory volume above (VTa) and
      below (VTb) the leak divided by VTa and multiplied by 100. Ci and Ri were
      analyzed conventionally and by linear regression. Percent error of Ci was defined
      as the difference between inspiratory compliance above the leak (Cia) and below
      the leak (Cib) divided by Cia and multiplied by 100. The results showed that the
      inspiratory time (Ti) of the ventilatory setting is the most important factor for
      determining %leak. Percent error of Ci is in proportion to %leak. The change in
      inspiratory resistance is complicated, depending on the ventilatory setting, leak
      site resistance and the method of analysis. This study demonstrates the origin of
      the computational error in breaths with ETT leakage diagramatically and by use of
      mathematics. It suggests that air leakage may contribute to a high variability in
      compliance and resistance measurements.

PMID- 8857255
TI  - Excimer laser photorefractive keratectomy for myopia.
AB  - To evaluate the safety, effectiveness and stability of excimer laser
      photorefractive keratectomy (PRK) treatment, we studied its posttreatment results
      in 44 normal-sighted myopic eyes where a 193-nm emission wavelength excimer laser
      was used to correct myopia. The eyes were divided into three groups according to
      the preoperative refractive error and attempted correction: group I, preoperative
      myopia < or = 6.00 diopters (D), full correction; group II, preoperative myopia
      between 6.00 and 8.00 D, full correction; group III, preoperative myopia > 8.00
      D, attempted correction of 8.00 D. Percentages of relative spherical equivalents
      (ie, observed spherical equivalent -- expected spherical equivalent) within +/-
      1.0 D 3 months after treatment were 95% in group I, 64% in group II and 67% in
      group III. Uncorrected visual acuity of 20/40, or better, was achieved in 100% of
      eyes in group I, and 92% in group II at 6 months. Initial overcorrection followed
      by myopic regression was observed in all groups. The refractive outcome in our
      study was stable 3 months after surgery. Anterior stromal haze was mild and
      disappeared gradually 3 months postoperatively. The greater the diopter
      correction needed, the higher the grade of corneal haze (p < 0.01). There were no
      significant complications. The results of this study demonstrated that excimer
      laser PRK appears to be a reasonably predictable and stable procedure to correct
      low to moderate myopia.

PMID- 8857256
TI  - Implications of prolonged fetal heart rate deceleration during the second stage
      of labor.
AB  - In order to evaluate the neonatal outcomes of infants who had prolonged fetal
      heart rate (FHR) deceleration during the second stage of labor, the neonatal
      outcomes of 24 infants born after vaginal delivery at 37 to 42 weeks of gestation
      with prolonged FHR deceleration during the second stage of labor were compared
      with the outcomes of 28 infants of a similar gestational age who had normal FHR
      patterns. No differences in the Apgar scores, mean umbilical PaCO2, PaO2, HCO3-
      or base deficit values were observed between the two groups, but the mean pH
      values differed significantly. The occurrences of a 1-minute Apgar score < 7,
      umbilical arterial pH < 7.20, presence of meconium and admission to the neonatal
      intensive care unit were higher in the study group, but were not significantly
      different. None of the 24 infants with prolonged FHR deceleration experienced
      birth trauma, meconium aspiration, neonatal seizure or neonatal death, but three
      were found to have congenital heart disease. We conclude that prolonged FHR
      deceleration during the second stage of labor without FHR abnormalities during
      the first stage of labor is not always associated with an adverse neonatal
      outcome and does not mandate the need for surgical or immediate vaginal delivery.
      Their appearance on FHR tracings requires the implementation of additional
      methods to assess fetal well-being and also to diagnose fetal distress.

PMID- 8857257
TI  - Induction of superoxide dismutase isozymes by tumor necrosis factor-alpha and
      lipopolysaccharide in cultured normal and hyperplastic gingival fibroblasts.
AB  - To determine whether lipopolysaccharide (LPS) and tumor necrosis factor-alpha
      (TNF-alpha) are involved in the induction of superoxide dismutase (SOD) in
      gingival tissue, we examined their effect on induction of SOD isozymes in
      cultured normal (NGF) and phenytoin-induced hyperplastic (PHF) gingival
      fibroblasts. Treatment of both NGFs and PHFs with 10 to 50 ng/mL TNF-alpha for 24
      hours increased the level of manganese SOD (MnSOD) to as much as four times the
      level of untreated cultures. PHFs, but not NGFs, were shown to be responsive to
      TNF-alpha in eliciting a significant increase in copper-zinc SOD (Cu/ZnSOD),
      albeit in a lesser amount than MnSOD. Additionally, treatment of both types of
      cells with 5 to 50 mg/mL of LPS for 24 hours also elicited an increase in the
      levels of MnSOD. Again, an LPS-induced increase in Cu/ZnSOD levels could only be
      demonstrated in PHFs, but not in NGFs. These observations were further confirmed
      by comparing the achromatic bands associated with SOD isozymes exhibited in the
      electrophoretogram using a nondenaturing polyacrylamide electrophoresis
      technique. These results indicate that TNF-alpha and LPS were capable of inducing
      both MnSOD and Cu/ZnSOD simultaneously in PHF fibroblasts. PHFs may be inherently
      more capable than NGFs in combating oxidative stress.

PMID- 8857258
TI  - Adverse drug reactions in a medical ward.
AB  - The preliminary results of an interdisciplinary active surveillance adverse drug
      reaction (ADR) reporting program conducted from April 1992 to December 1993 in
      the family medicine ward of National Taiwan University Hospital are presented.
      During this period, every admitted patient was screened for any possible drug
      related problems; suspected ADRs were evaluated and documented. The USA Food and
      Drug Administration's definition of ADR was used, and Naranjo's scale was used to
      estimate the probability of drug-induced events. A total of 41 ADRs were
      identified in 38 patients. Among these 41 cases, 18 ADRs occurred during
      hospitalization, and 23 were the reason for hospitalization. The incidence of
      ADRs rated as probable or highly probable during hospital stay was 2.0%, or 2.7%
      if possible reactions were included (based upon 666 hospital admissions to the
      unit during the study period). The occurrence of admissions due to ADRs rated as
      highly probable or probable was 2.7%, or 3.5% if possible reactions were
      included. Twenty-one ADRs (51.2%) were type A reactions and 20 (48.8%) were type
      B. Thirty-three ADRs (80.5%) were classified as serious or moderate. There was no
      mortality. Further studies are warranted to determine the incidence of ADRs in
      different patient populations in Taiwan.

PMID- 8857259
TI  - Hemosuccus pancreaticus from a splenic artery pseudoaneurysm: an unusual cause of
      upper gastrointestinal bleeding.
AB  - Hemorrhage through the pancreatic duct into the duodenum, so called "hemosuccus
      pancreaticus", is a rare cause of gastrointestinal bleeding with diagnostic
      difficulties. We report a 60-year-old man with recurrent upper gastrointestinal
      bleeding due to rupture of a splenic artery pseudoaneurysm into the pancreatic
      duct. Initial upper gastrointestinal endoscopy failed to identify the site of the
      hemorrhage. Abdominal computed tomography disclosed a cystic mass containing a
      well-enhanced spherical area at the pancreatic tail. Arterial blood flow was
      demonstrated in the lesion by Doppler ultrasound. Celiac angiography demonstrated
      a saccular pseudoaneurysm arising from the splenic artery. Bleeding from the
      ampulla of Vater located in a big duodenal diverticulum was found on repeat
      endoscopy. Surgical resection of the pseudoaneurysm with distal pancreatectomy
      and splenectomy was successfully performed. The patient remained symptom-free 5
      months after the operation. Hemosuccus pancreaticus, although rare, remains
      important in the differential diagnosis of upper gastrointestinal bleeding of
      obscure origin.

PMID- 8857260
TI  - Intrathecal morphine for neuropathic pain in a pregnant cancer patient.
AB  - Although they have been documented, opioid treatments in obstetrics are mostly
      limited to methadone maintenance treatment in pregnant addicts or
      analgesia/anesthesia for labor. A literature search revealed no previous studies
      describing analgesic techniques for relief of severe cancer pain in pregnant
      patients. As response to morphine is dose-dependent, its conventional use can be
      problematic in pregnant women suffering from severe cancer pain because it is
      important to prevent opioid intoxication of the fetus. Furthermore, long-term
      exposure to morphine may result in physical dependence on the drug by the fetus,
      causing acute withdrawal syndrome and growth retardation after delivery. We
      report our experience in treating a 35-year-old pregnant female, in her 32nd
      gestational week, suffering from neuropathic pain due to advanced ovarian cancer.
      Using a microcatheter technique, we administered small doses of morphine
      intrathecally and successfully controlled the pain before delivery without
      complications in the mother and fetus. Treatment options of systemic vs spinal
      and epidural vs intrathecal opioids under such unique circumstances are
      discussed.

PMID- 8857261
TI  - Mediastinal lymphangioma in an infant.
AB  - Lymphangioma confined exclusively to the mediastinum occurs rarely in patients
      under 2 years of age. A 17-month-old girl presented with recurrent respiratory
      symptoms and signs. Chest radiographs taken at 9 and 17 months of age showed a
      large mediastinal mass, which had increased in size during the interval.
      Sonography revealed the mass to be cystic and multiloculated. Magnetic resonance
      imaging demonstrated a heterogeneous mass lying in the anterior and superior
      mediastinum and enveloping the great vessels. The child underwent a left
      thoracotomy and the tumor was almost completely removed. The pathologic diagnosis
      was cavernous lymphangioma. The postoperative course was uneventful.
      Lymphangioma, though rare, should be considered in the differential list of
      mediastinal tumors and cysts in infants.

PMID- 8857262
TI  - Continuous monitoring of venous oxygen saturation in critically-ill infants.
AB  - A 4-French gauge Opticath catheter, inserted into a neonate's right atrium
      through the right internal jugular vein, can be used to continuously monitor
      venous blood oxygen saturation in the right atrium. This method instantly detects
      subtle changes in cardiopulmonary function in small infants and neonates and
      enables the appropriate treatment to be given in cases of critical infantile and
      neonatal cardiopulmonary deterioration. This report discusses four neonatal and
      infantile patients who underwent continuous monitoring of venous blood oxygen
      saturation in the right atrium. Continuous monitoring allowed appropriate
      treatment to be given earlier compared to conventional monitoring methods of
      blood pressure and heart rate.

PMID- 8857263
TI  - Exfoliation syndrome.
AB  - Increasing pathophysiologic evidence indicates that exfoliation syndrome, a
      systemic process involving various visceral organs, frequently manifests itself
      first in the eyes as exfoliation of the lens and glaucoma. Exfoliation syndrome
      occurs when several tissues synthesize an abnormal basement membrane protein.
      This protein may obstruct the trabecular meshwork in the eye and cause glaucoma.
      We present a case of exfoliation syndrome associated with angle-closure glaucoma
      in a 57-year-old male patient from Taiwan. After peripheral iridectomy and
      topical antiglaucoma medications, intraocular pressure in both eyes was well
      controlled in the range of 15 to 20 mmHg. The mechanism of the glaucomatous optic
      neuropathy in this patient was probably caused by chronic angle-closure glaucoma
      superimposed with the exfoliation syndrome.

PMID- 8857264
TI  - Pituitary abscess: CT and MRI findings.
AB  - We report a patient with a pituitary abscess which was incidentally found after
      he had sustained a head injury. This 61-year-old man had no clinical or
      laboratory evidence suggestive of a pituitary lesion. A precontrast-enhanced
      brain computed tomograph (CT) showed a slightly hyperdense tumor. Magnetic
      resonance imaging (MRI) showed hyperintensity on T1-weighted images, but central
      hypointensity with peripheral ring-form hyperintensity on proton density-weighted
      and T2-weighted images. These CT and MRI characteristics may have been
      attributable to the abundant proteinaceous content of the abscess. Therefore, the
      appearance of a pituitary abscess in image studies may be variable depending on
      the abscess composition.

PMID- 8857265
TI  - Isolation and characterization of a new arsenic methylating bacterium from soil.
AB  - An arsenic resistant and arsenic methylating bacterium belonging to the
      Flavobacterium-Cytophaga group was isolated from soil with an arsenic content of
      1.5 ppm. The growth of the bacterium is enhanced in the presence of As compounds
      in concentrations up to 200 ppm in the cultural media with a stronger effect of
      As(V) than of As(III) compounds. As a volatile product of the methylation of both
      NaH2AsO3 and NaH2AsO4 exclusively, Me3As was formed and detected by mass
      spectrometry. Quantitative aspects of the methylation were studied with GC/MS.
      The intracellular accumulation of arsenic in the methylating strain was compared
      with two non methylating strains from the same soil.

PMID- 8857267
TI  - Influence of phosphate on development of the nematode-trapping fungus
      Arthrobotrys oligospora.
AB  - Arthrobotrys oligospora captures and digests nematodes by means of adhesive
      networks. These traps are formed in the presence of nematodes but can also be
      induced by low nutrient media containing amino acids. Influence of phosphate on
      growth and development of A. oligospora was studied in a liquid culture system
      known to allow heavy trap formation. Substrate-induced but not nematode-induced
      trap, formation was inhibited by phosphate at concentrations above 30 mu M. High
      numbers of chlamydospores were formed in aging cultures irrespective of phosphate
      concentration.

PMID- 8857266
TI  - Isolation and partial characterization of polymyxin B-resistant isolates of
      Vibrio parahaemolyticus.
AB  - Two polymyxin-resistant isolates V2PXR and P1R4PXR of Vibrio parahaemolyticus
      were spontaneously isolated and compared with the polymyxin-sensitive strains as
      to their chemical compositions of cell envelopes and their outer membrane protein
      compositions. When grown in the presence or absence of polymyxin, the cell
      envelopes of polymyxin-resistant isolates showed a significantly increased
      content of protein as compared with those of respective polymyxin-sensitive
      strains. Both polymyxin-resistant isolates produced the major outer membrane
      protein b' after growth in the presence or absence of polymyxin. A new major
      outer membrane protein with an apparent molecular weight of 26,000 (26 K protein)
      was produced by polymyxin-resistant isolates grown in the presence of polymyxin.
      The production of 26 K protein was also observed in the polymyxin-resistant
      isolates grown in the medium containing low concentrations of NaCl (0.2% and
      0.5%).

PMID- 8857268
TI  - Long-term effects of restrictive culture conditions on Saccharomyces cerevisiae
      sec7 cells.
AB  - Long-term effects of restrictive conditions on the temperature-sensitive S.
      cerevisiae sec7 mutant were studied. By microscopic analysis no cell lysis could
      be detected of cells cultured for up to 19 days at 37 degrees C. The optical
      density as well as the cell number remained constant during the whole period
      under restrictive conditions. However, restrictive conditions decreased the
      incorporation of 35S-methionine into intracellular proteins in a reversible
      manner indicating that protein biosynthesis was inhibited whereas the cells
      remained alive. Northern blot experiments revealed that restrictive conditions
      did not markedly decrease the ratio of the mRNA levels to total RNA for the genes
      TEF1, TEF2, SUC2, and BGL2 up to 73 hours. However the content of total RNA
      decreased drastically with increasing incubation times at restrictive
      temperature. In spite of the reduced total RNA content, cells are capable of new
      synthesis of mRNA under restrictive conditions which was shown by incubation of
      the cells in the presence of actinomycin D--an inhibitor of the mRNA synthesis.
      Most of the cells which survived a long-term incubation at 37 degrees C are not
      able to divide and to form colonies immediately after their transfer to
      permissive conditions.

PMID- 8857269
TI  - Influence of relA locus on electrophoretic mobility of a stringent/relaxed
      Escherichia coli K 12 strain pair.
AB  - Stringent (relA+) and relaxed (rel A-) controlled Escherichia coli cells differ
      in their regulation of many biochemical pathways such as phospholipid and
      lipopolysaccharide metabolism (LPS) after amino acid limitation. Because such
      differences could result in various cell envelopes, cells of stringent controlled
      E. coli strain CP78 (relA+) and relaxed controlled E. coli strain CP79 (relA)
      were studied regarding their electrophoretic mobility. The graphs of the mobility
      distributions of both strains were different: cells of strain CP79 caused
      secondary peaks in addition to the main peaks whereas the mobility distributions
      of cells of strain CP78 showed only one maximum. In the pH range from 6.0 to 8.0
      the location of the main peaks of cells of strain CP79 were changed to less
      negative values after induction of relaxed response. In contrast to this the
      stringent response in strain CP78 caused no change of the mobility distributions.

PMID- 8857270
TI  - Influence of the herbicide bentazon on soil microbial community.
AB  - Changes in microbial numbers and activities in a soil in response to bentazon
      applied at 10 and 100 ppm were studied after 4 and 30 weeks of incubation in
      laboratory conditions. As regards the eight general and functional microbial
      groups studied (aerobic and anaerobic bacteria, fungi, aerobic and anaerobic N2
      fixing bacteria, nitrifiers, aerobic and anaerobic cellulolytic microorganisms),
      only the number of anaerobic N2-fixing bacteria significantly decreased, in the
      presence of the highest herbicide concentration for 30 weeks. At both the
      incubation times, only the higher dose of bentazon markedly inhibited soil
      nitrification and CO2 emission. Methanogenesis was inhibited by 1000 ppm bentazon
      added to anaerobic liquid cultures containing 5% soil for at least 2 weeks. There
      was an incomplete recovery of the herbicide at the two incubation times: < 5% of
      10 ppm after 4 weeks and about 30% of 100 ppm after 30 weeks. No biodegradation
      of the compound was observed in liquid cultures under aerobic or anaerobic
      conditions. It is concluded that a bentazon concentration no higher than the
      field rate distributed within a 2-cm layer of soil does not considerably affect
      the microflora even in the absence of microbial degradation.

PMID- 8857271
TI  - Diarrheal and environmental isolates of Aeromonas spp. produce a toxin similar to
      Shiga-like toxin 1.
AB  - Diarrheal and environmental isolates of 39 strains of Aeromonas spp. were studied
      for detection of virulence factors. Although these 39 strains did not produce
      either heat-labile or heat-stable enterotoxins, culture filtrates of 31 strains
      produced cytopathic effects on Vero cells. Among these, culture filtrates of
      three strains of Aeromonas hydrophila and one strain of Aeromonas caviae could be
      neutralized by Escherichia coli O157:H7 Shiga-like toxin 1 antiserum. A single
      band of plasmid DNA of 2.14 kbp was isolated from these strains of Aeromonas spp.
      and E. coli O157:H7, which could be amplified by the polymerase chain reaction
      (PCR), employing oligonucleotide primers from the Shiga-like toxin 1 (SLT1) gene
      of E. coli O157:H7. E. coli HB 101 cells when transformed with the same plasmid
      showed cytopathic effects on Vero cells, which indicates that the SLT 1 homolog
      gene(s) of Aeromonas spp. is plasmid encoded. These results suggest that
      Aeromonas spp. may also produce Shiga-like toxin 1, or at least a cytotoxin with
      some homology with the Shiga-like toxin 1 of E. coli O157:H7.

PMID- 8857272
TI  - Glycoside and polysaccharide hydrolase activity of the rumen anaerobic fungus
      Caecomyces communis (Sphaeromonas communis SENSU ORPIN) at early and final stages
      of the developmental cycle.
AB  - The rumen anaerobic fungus Caecomyces communis was grown in a fermentor in Lowe
      medium. We studied four polysaccharide hydrolases and three glycoside hydrolases
      at early and final stages. We found a difference in cell association for these
      enzymes depending on the developmental stage. The endocellulase and beta-D
      fucosidase were early synthesized, and their activities decreased at the end of
      the developmental cycle. On the contrary, the beta-D-glucosidase, beta-D
      xylosidase and xylanase activities increased during the cycle. The avicelase and
      the CM-cellulase activities linked with thalli increased, whereas the
      extracellular activities of these enzymes decreased.

PMID- 8857273
TI  - Starvation-induced multiresistance in Enterococcus faecalis JH2-2.
AB  - Compared with growing bacteria, carbohydrate-starved cells of Enterococcus
      faecalis show development of a multiresistance state against heat, H2O2, acid,
      and ethanol, but not against UV irradiation. The kinetics of acquisition of
      resistance is different according to the stress. Three hours of starvation
      provide maximal resistance against ethanol, while the tolerance to heat, H2O2,
      and acid increases progressively with the duration of starvation. Chloramphenicol
      treatment does not abolish the ethanol tolerance. Protein synthesis inhibition
      during the transitional growth phase and the first hours of starvation partially
      inhibit the acquisition of heat and oxidative resistances. Antibiotic treatment
      after 3 h of starvation does not affect the increase of these resistances. We
      suggest that synthesis of specific proteins revealed by 2-D gel analysis in the
      first 3 h of starvation, followed by a second mechanism related to protein
      degradation or alteration, is necessary for acquisition of maximal resistance
      towards heat and oxidative stresses.

PMID- 8857274
TI  - A phage-mediated transfer of chromosomally integrated tetracycline resistance
      plasmid in Staphylococcus aureus.
AB  - The ability of a Staphylococcus aureus isolate WBG7416 to transfer its resistance
      determinants was studied in conjugation and mixed-culture transfer experiments.
      It carried plasmid-borne resistance to kanamycin, trimethoprim, chloramphenicol,
      cadmium, propamidine isethionate, and chromosomal resistance to methicillin,
      gentamicin, streptomycin, erythromycin, clindamycin, tetracycline, and
      minocycline. It transferred tetracycline resistance in mixed-culture transfer but
      not in conjugation experiments. DNA-DNA hybridization of genomic DNA from the
      tetracycline-resistant transferrants against a labeled tetracycline resistance
      plasmid, pWBG3, probe revealed the presence of an integrated plasmid in their
      chromosomes. In contrast, no homology to the probe was detected in the chromosome
      of a tetracycline-resistant mutant of the recipient strain. The results
      established a role for a bacteriophage in the transfer of chromosomal
      tetracycline resistance in WBG7416 besides demonstrating the presence of an
      integrated tetracycline resistance plasmid in the transferrants. It also offered
      an insight into the nature of the integrated plasmid.

PMID- 8857275
TI  - Growth inhibition of Pseudomonas aeruginosa and Enterococcus faecalis by crude
      extractives of Mansonia altisima timber sawdust.
AB  - Crude, aqueous methanol and ethanol extracts of sawdust of Mansonia (Mansonia
      altisima) timber inhibited Pseudomonas aeruginosa and Enterococcus faecalis. The
      minimum inhibitory concentration ranged from 4.4 to 9.3 mg/ml, while the minimum
      bactericidal concentration was 10.0-25.0 mg/ml. Enterococcus faecalis was more
      susceptible, but no marked difference occurred in the antibacterial effect of
      methanol and ethanol extracts. The aqueous extract was less active.

PMID- 8857276
TI  - Accumulation of VDT work-related visual fatigue assessed by visual evoked
      potential, near point distance and critical flicker fusion.
AB  - To confirm daily accumulation of visual fatigue induced by work with visual
      display terminals (VDT), visual evoked potential (VEP), near point distance (NPD)
      and critical flicker fusion (CFF) were measured in three VDT workers and three
      sex- and age-matched controls (non-VDT workers) in the morning, noontime and
      evening for five consecutive days (Monday to Friday), totally 15 times per
      subject. The workers had been engaged in wireless handling operation, with VDTs,
      of an unmanned power shovel (Worker 1), an unmanned 78-ton dump truck (Worker 2)
      and mobile monitor-cameras (Worker 3), for 10 months. Their working hours were
      about 6.5 hours per day; but, the Worker 2 could take a 10-minute recess (a
      period without VDT work) per about 30 minutes during working hours. Significant
      daily variations in the VEP latency, NPD and CFF were found in the Worker 1 or
      Worker 3 despite the absence of any significant daily or diurnal variations in
      the non-VDT workers; the trends in the variations were getting worse from Monday
      to Friday. The NPD in the VDT workers was significantly longer than that in each
      of the matched controls; also, the CFF in the Workers 1 and 3 was significantly
      depressed. The changes in the VEP latency from morning to noontime and in the NPD
      and CFF from noontime to evening were significantly larger in the VDT worker than
      in the matched control. These findings suggest that VDT work probably affects
      visual function assessed by the VEP, NPD and CFF. Visual fatigue due to long-term
      VDT work may tend to be accumulated day by day.

PMID- 8857277
TI  - Time series investigation of job-events and depression in computer software
      engineers.
AB  - The aim of the present study is to conduct an observation of a time series of job
      event/life event and depressive symptoms, prospectively. Ten male computer
      software engineers were observed every two weeks for five months and every
      following week for two months. In total, one hundred and eighty-one observations
      were made. A semi-structured interview was conducted to survey the week-unit job
      events on each sampling day. The depressive symptoms were measured using Zung's
      Self-reporting Depressive Scale (SDS). It was found that the events had a
      significant effect on the SDS raw score. It also showed that the effective time
      period of the events on depression is within two weeks. With a week-based
      analysis in a prospective approach, the present study showed the immediate
      effects of job events or life events on depressive symptoms.

PMID- 8857278
TI  - Studies on fatigue of night duty workers at a newspaper office.
AB  - Fatigue of night duty workers in different divisions of a newspaper office was
      investigated by physiological methods such as the Blinker, Flicker and grip
      methods. The relationship between fatigue and hematological parameters such as
      hemoglobin (Hb), the hematocrit (Ht), serum-free amino acid levels, and indices
      of liver function such as the GOT and GPT levels were also examined. The
      composing and press room workers mainly complained of the subjective symptom of
      muscle fatigue, while workers in the photo-engraving and editorial departments
      mainly complained of mental fatigue. The overall rate of fatigue in the newspaper
      office was about 38.1%, but varied from one division to another, being especially
      high in the photo-engraving and editorial departments. The subjects with fatigue
      had low levels of serum GOT and GPT and high levels of serum-gluconeogenic amino
      acids, such as aspartic acid, glutamic acid, prolin, glycine, and alanine. These
      altered levels of serum-free amino acids and GOT and GPT seemed to be due to
      increased secretion of adrenal corticoid hormone caused by the stress of fatigue.

PMID- 8857279
TI  - An experimental study on changes in finger blood pressure during chain-saw
      operation.
AB  - In this study finger blood pressure was observed by using a new method to
      determine if vasoconstriction activated by sympathetic nervous system takes part
      in changes in peripheral circulation with exposure to vibration, noise and tool
      weight. Finger blood pressure was measured every one minute by ambulatory
      monitoring system. The time profile of a single experiment consisted of 5 minutes
      pre-exposure period followed by one exposure period lasting 2 minutes and a post
      exposure period of 5 minutes. Measurement was carried out as a factorial
      experiment of combination of vibration (17.8 m/s2 in X-axis, 20.0 m/s2 in Y-axis
      and 50 m/s2 in Z-axis), noise (105 dBA) and tool weight (7.9 kg). Finger blood
      pressure increased significantly under the following conditions: vibration +
      noise + tool weight > vibration + noise .=. vibration .=. tool weight > noise .=.
      control. During exposure period the combination with vibration, noise and finger
      grip exercise induced 29.7 mmHg of increases on average in finger blood pressure.
      On the other hand, finger blood pressure was increased 9.5 mmHg by vibration
      alone. These results agreed with our previous studies which observed the
      decreases of finger skin temperature and finger blood flow during the same
      conditions. The present study suggests that possible activation of the
      sympathetic nervous system may be involved in the physiological mechanisms of the
      changes in blood flow during chain-saw operation.

PMID- 8857280
TI  - Status of health promotion program implementation and future tasks in Japanese
      companies.
AB  - This study was performed to elucidate the status of the implementation of health
      promotion programs (HPPs) and future tasks in occupational settings in Japan. A
      survey was conducted using a multiple type questionnaire mailed to 395 companies
      throughout Japan in 1993. The questionnaire was mailed back, after having been
      answered anonymously, with a response rate of 59%. Companies with more than 300
      employees accounted for 76% of the sample. Approximately 70% of the companies
      implemented HPPs of which health guidance and fitness programs were the two most
      frequently adopted programs. Nutrition education and mental health programs
      seemed to be emphasized as future possibilities. Smoking cessation programs were
      not as common as segregation policies, such as zoning of smoking areas.
      Currently, 45% of the companies used only in-house health personnel for HPPs, but
      the prospective percentage in the future was 24%. Most of the companies shared
      the cost of HPPs with a Health Insurance Society. Lack of health personnel and
      budgetary restrictions on HPPs constituted the major barriers to the
      implementation of HPPs. Small-scale enterprises were noted to be particularly
      influenced by these barriers.

PMID- 8857281
TI  - A 100 mT-class ELF magnetic field exposure system for cultured cells.
AB  - We developed a system for exposure of cultured cells to extremely low frequency
      (ELF) magnetic fields much stronger than those used in previous in vitro studies.
      The system consists of an electromagnet, a commercial incubator with a custom
      designed door and a custom-designed shelf, and other components, and exposes
      cells in the incubator to ELF magnetic field. We confirmed that it has good
      performance characteristics in terms of field intensity, field uniformity,
      waveform, field stability, temperature uniformity, and temperature stability. Its
      features include: (1) strong ELF magnetic fields (at most, 170 mTRMS), (2) long
      term exposure (at least, 5.5 h), and (3) variable frequencies (10-100 Hz). This
      exposure system is expected to contribute significantly to research on possible
      hazards of ELF magnetic fields.

PMID- 8857282
TI  - Breakthrough times for vapors of organic solvents with low boiling points in
      steady-state and pulsating flows on respirator cartridges.
AB  - The breakthrough times of five organic solvents at various vapor concentrations
      were measured in steady-state and pulsating flows on commercially available
      respirator cartridges. The relationship between the logarithmic vapor
      concentration and the logarithmic breakthrough time of each organic solvent
      showed an inverse correlation in both of the flow patterns. The organic solvents
      with lower boiling points exhibited the shorter breakthrough times in both of the
      flow patterns. The ratios of the breakthrough times in the pulsating flow to
      those in the steady-state flow were lower than 0.9 when the vapor concentrations
      were higher than 600 ppm for ethyl acetate, methyl acetate, acetone and
      dichloromethane. From the present study, the breakthrough in the pulsating flow
      tends to occur earlier than in the steady-state flow when using a highly
      concentrated vapor of an organic solvent with a low boiling point.

PMID- 8857284
TI  - Antinucleolar autoantibody induced by mercuric chloride in mice: does sodium
      selenite inhibit autoantibody production?
AB  - Repeated exposure of subtoxic doses of mercuric chloride (HgCl2) can induce
      antinucleolar autoantibodies in susceptible mice. To study the immunopathological
      mechanism(s), sodium selenite (Na2SeO3), which is known to reduce the toxicity of
      mercury, is injected simultaneously with HgCl2 into mice. Equimolar Na2SeO3 nor
      the same amount of Se in Na2SeO3 as Hg in HgCl2 could not reduce antinucleolar
      autoantibody induction by HgCl2. These results indicate that the mechanism of
      autoimmunity induction by HgCl2 might be independent of its toxicity.

PMID- 8857283
TI  - Adaptation of circadian corticosterone and catecholamine rhythms to light-dark
      cycle reversal in the rat.
AB  - Circadian rhythms of urinary excretion of corticosterone and catecholamines were
      examined in the rat before and after phase reversal of a 12-hour light and 12
      hour dark cycle. After the reversal, the acrophase of rhythm was delayed and
      became constant again on the 6th day for corticosterone and on the 7th or 8th day
      for adrenaline. The ratios of light-period output to 24-hour output of adrenaline
      and noradrenaline, however, adjusted to the new light-dark cycle on 10th day,
      whereas this ratio became constant on 6th day for corticosterone. Thus, circadian
      corticosterone rhythm seems to adapt to light-dark reversal more quickly than
      catecholamine rhythm.

PMID- 8857286
TI  - Surface sampling isn't widely applicable.

PMID- 8857285
TI  - Characterization of steroid/cyclodextrin inclusion compounds by x-ray powder
      diffractometry and thermal analysis.
AB  - Two inclusion compounds, progesterone with beta- and gamma-cyclodextrin, were
      studied with X-ray powder diffractometry and thermal analysis. Disappearance of
      characteristic X-ray diffraction patterns of the two compounds as well as the
      appearance of a new diffraction pattern for each were found when formation of the
      inclusion compounds was completed. The X-ray diffraction patterns of beta
      cyclodextrin measured at various temperatures showed a structural change
      occurring between 60 degrees C to 80 degrees C, which coincided well with the DSC
      endothermic peak around 75 degrees C. Results suggest that changes in the X-ray
      diffraction patterns of cyclodextrin during inclusion formation and during
      heating is due to the displacement of adsorbed water by progesterone in the
      cavity of cyclodextrin.

PMID- 8857287
TI  - NLRB intrusions are dangerous.

PMID- 8857288
TI  - Developing new safety markets.

PMID- 8857290
TI  - Providing first aid assistance in confined spaces.

PMID- 8857289
TI  - Stop the bleeding at industrial sites.

PMID- 8857291
TI  - Workplace AIDS/HIV: are you immune?

PMID- 8857292
TI  - Same game, new strains. Learn how to recognize TB's warning signs.

PMID- 8857293
TI  - Triple compliance: FMLA, ADA, and workers' comp.
AB  - The major nightmare many employers have encountered is that they fail to notify
      an employee out on workers' comp leave in writing that the FMLA leave period
      began when they stopped working.

PMID- 8857294
TI  - Alternative cures for workers' comp injuries.
AB  - Despite the AMA's skepticism, employers are using chiropractic and preventive
      acupuncture. Is homeopathy next?

PMID- 8857295
TI  - Disabled doesn't mean deficient.

PMID- 8857296
TI  - ASTM completing long-awaited apparel standards.

PMID- 8857297
TI  - The lockout/tagout missing link: maintenance.
AB  - Often employees provide a false economy--saving time, balancing schedules, and
      then moving on to the next task. This motive is well intentioned, however
      misguided.

PMID- 8857298
TI  - State-of-the-art burn treatment.
AB  - The death rate per 100,000 workers fell to just four in 1994, but there were 3.5
      million disabling injuries. The cost associated with deaths and injuries was
      $120.7 billion that year.

PMID- 8857299
TI  - Colorimetric tubes: cost-effective gear in the IH toolbox.

PMID- 8857300
TI  - Cytokine gene-modified vaccines in the therapy of cancer.
AB  - Therapeutic strategies based on the insertion of cytokine genes into the genome
      of tumour cells, followed by vaccination with the resulting genetically modified,
      cytokine-producing cells, represent a new potential prospect for treatment of
      cancer patients. In this review, the concept of cytokine gene-modified cancer
      vaccines is discussed; the discussion is focused on the rationale,
      characterization, progress in the development, preclinical testing, and first
      clinical trials. An effort is made to analyse and integrate the results obtained
      in different experimental model systems in order to determine the needed
      approaches and directions for further research.

PMID- 8857301
TI  - Chronobiotics--drugs that shift rhythms.
AB  - A chronobiotic is defined and levels of action within the mammalian circadian
      pacemaker system, such as the retina, retinohypothalamic tract,
      geniculohypothalamic tract, suprachiasmatic nuclei, output and feedback systems
      are identified. Classes of drug that include the indoleamines, cholinergic
      agents, peptides, and benzodiazepines, which might act as chronobiotics within
      these levels, are evaluated. Particular emphasis is placed on the indole,
      melatonin (MLT). The clinical circumstances for use of chronobiotics in sleep
      disturbances of the circadian kind, such as jet lag, shift work, delayed sleep
      phase syndrome, advanced sleep-phase syndrome, irregular and non-24-hr sleep-wake
      cycles, are described under reorganized headings of disorders of entrainment,
      partial entrainment, and desynchronization. Specific attention is given to the
      blind and the aged. Both human and animal studies suggest that MLT has powerful
      chronobiotic properties. MLT shows considerable promise as a prophylactic and
      therapeutic alternative or supplement to the use of natural and artificial bright
      light for resetting the circadian pacemaker. Throughout this discussion, the
      hypnotic and hypothermic versus the chronobiotic actions of MLT are raised.
      Finally, problems in the design of delivery systems for MLT are discussed.

PMID- 8857302
TI  - How has molecular pharmacology contributed to our understanding of the
      mechanism(s) of general anesthesia?
AB  - This review discusses the mechanism(s) of general anesthesia from a
      pharmacological viewpoint; in particular, the ability of drugs to produce many
      different effects is emphasised. The problems of experimental measurement of
      general anesthesia are discussed, and the possibilities for antagonism and
      potentiation of anesthesia considered. Physicochemical studies on anesthesia are
      described, as are the advancement of ideas beyond consideration of lipids and
      proteins as separate sites of action. The importance of studies on different
      areas of the brain is highlighted, and the review finishes with a survey of the
      effects of general anesthetics on synaptic transmission which emphasises the
      problems of extrapolation from in vitro to in vivo.

PMID- 8857303
TI  - Adrenergic mechanisms in the control of gastrointestinal motility: from basic
      science to clinical applications.
AB  - Over the years, a vast literature has accumulated on the adrenergic mechanisms
      controlling gut motility, blood flow, and mucosal transport. The present review
      is intended as a survey of key information on the relevance of adrenergic
      mechanisms modulating gut motility and will provide an outline of our knowledge
      on the distribution and functional role of adrenoceptor subtypes mediating motor
      responses. alpha1-Adrenoceptors are located postsynaptically on smooth muscle
      cells and, to a lesser extent, on intrinsic neurons; alpha2-adrenoceptors may be
      present both pre- and postsynaptically, with presynaptic auto- and hetero
      receptors playing an important role in the modulation of neurotransmitter
      release; beta-adrenoceptors are found mainly on smooth muscle cells. From a
      clinical standpoint, adrenoceptor agonists/antagonists have been investigated as
      potential motility inhibiting (antidiarrheal/antispasmodic) or prokinetic agents,
      although at present their field of application is limited to select patient
      groups.

PMID- 8857304
TI  - The chemotherapeutic effects of H+/K+ inhibitors on Helicobacter pylori
      infection.
AB  - Helicobacter pylori's powerful urease enzyme is essential for colonisation and
      adaptation to the acid milieu of the stomach. Eradication of infection with
      "standard triple therapy" abolishes the chronic immunological and inflammatory
      responses to H. pylori and, thus, cures gastritis and peptic ulcer. In vitro,
      proton pump inhibitors (PPI) are active against H. pylori with minimum inhibitory
      concentrations that compare favourably with bismuth salts. PPIs are also potent
      urease inhibitors, but because PPIs are also active against urease-negative
      mutant Helicobacter spp., it is unlikely that urease inhibition alone accounts
      for their anti-H. pylori activity. Early reports suggested that omeprazole
      monotherapy was able to eradicate H. pylori. This has not been confirmed by more
      comprehensive studies, which have shown that treatment with omeprazole is
      associated with a shift of infection from the antrum to the corpus. The
      explanation for this observation is unclear, but does not appear to be due to
      bacterial overgrowth. Raising the intragastric pH with a PPI lowers the minimum
      inhibitory concentration of the many antimicrobials, while decreasing the acid
      storage pool increases the intramucosal concentration. Dual therapy (omeprazole
      with either amoxycillin or clarithromycin) is a more logical and highly effective
      alternative to standard triple therapy, with fewer side effects and better
      patient compliance. However, H. pylori eradication regimens based on a PPI and
      two antimicrobials will be the first-line treatment for H. pylori gastritis and
      peptic ulcer in the future.

PMID- 8857305
TI  - Laser Doppler flowmetry: characteristics of a modified single-fibre technique.
AB  - The single-fibre percutaneous laser Doppler technique has been used in previous
      studies of intramuscular blood flow. This method facilitates studies of blood
      flow in deep tissue volumes and minimises the tissue trauma. The technique has
      been further developed with the aim of improving the signal quality. This has
      been accomplished by modifying the geometry of the fibre tip. By melting the
      fibre core material, lenses of different shapes are formed. Flat, spherical and
      'pear'-type tips have been manufactured and are evaluated theoretically and
      experimentally. The paraxial theory cannot accurately predict the position of
      zones of highest irradiance. Therefore, a ray-tracing program has been developed
      in the C language, by means of which some of the optical properties of the
      modified fibre tips can be simulated. Iso-irradiance graphs and beam profiles are
      calculated for the three different fibre tips. Measured and calculated irradiance
      curves are used for evaluation of the properties of the ray-tracing model. The
      three types of fibre tips are also evaluated and compared in flow models. The
      sphere and pear-type probes show a higher flow sensitivity than the flat-end
      type. These improvements in flow sensitivity are interpreted as being related to
      the larger, strongly irradiated tissue volumes in front of the fibres.
      Intramuscular measurements with the pear-type probe show high sensitivities to
      induced blood flow changes.

PMID- 8857306
TI  - Implantable multiprogrammable microstimulator dedicated to bladder control.
AB  - An implantable multiprogrammable microstimulator that is intended to restore
      normal bladder functions (retention and incontinence) to spinal cord injured
      patients is presented. The implantable microstimulator circuitry is externally
      controlled and is powered by a single encoded radio frequency carrier and has
      four bipolar (eight monopolar) independently controlled channels. It offers a
      higher degree of reprogrammability and flexibility and can be used in any
      neuromuscular applications. The implant system is adaptable to the patient's
      needs and to future developments in stimulation algorithms, without changing the
      implant. Features of the microstimulator include its capabilities to generate a
      wide range of waveforms and to combine up to four different programmable
      frequencies in each wave train. By using a forward error detection and correction
      communication protocol, the reliability of the implant is increased. The chip has
      been designed for structural testability by means of a scan-based test approach
      and uses circuit techniques to reduce power consumption and ensure long-term
      stability.

PMID- 8857307
TI  - Descriptive multidimensional statistical methods for analysing signals in a
      multifactorial biomedical database.
AB  - A methodology is presented to analyse multidimensional signals from several
      recording periods resulting from an experimental study on human or other living
      systems. The methodology is divided into two stages: intra-period analysis and
      inter-period analysis. The purpose of the first stage is to highlight general
      trends in multidimensional signal changes and the more informative components of
      the signals. The purpose of the second stage is to assess the influence of
      environmental or individual difference factors on a given signal component that
      appears to be discriminant in the first stage. To take into account the
      multivariable state of the system and the multi-observational aspect, a
      multidimensional descriptive statistical approach is used. The methods are
      correspondence analysis and hierarchical clustering. They are illustrated through
      an occupational medicine application from a study of sedentary posture.

PMID- 8857308
TI  - Computation of neuromagnetic fields using finite-element method and Biot-Savart
      law.
AB  - The finite-element method in combination with the Biot-Savart law is described to
      compute the magnetic field distribution generated by a dipolar source within a
      homogeneous volume conductor of an arbitrary shape. In order to calculate the
      three independent components of the magnetic field outside the volume conductor
      by means of the Biot-Savart law, the distribution of the current throughout the
      medium is required. A finite-element mesh is constructed using four-node
      tetrahedral elements. The potential in each node is computed numerically by the
      finite-element method using the proper continuity conditions across the
      boundaries. The gradient of the potential denotes the current density within an
      element. The components of the magnetic induction are calculated by numerical
      integration, applying the current density within the tetrahedrons. Simulations
      are carried out to assess the numerical accuracy for a homogeneous spherical
      volume conductor. Errors of 3% can be obtained with a locally refined spherical
      mesh containing about 1000 nodes, for dipoles at any depth and any orientation. A
      homogeneous realistically shaped model with the shape of the inside of the skull
      is obtained from magnetic resonance images.

PMID- 8857309
TI  - Importance of partitioning membranes of the brain and the influence of the neck
      in head injury modelling.
AB  - A head injury model consisting of the skull, the CSF, the brain and its
      partitioning membranes and the neck region is simulated by considering its near
      actual geometry. Three-dimensional finite-element analysis is carried out to
      investigate the influence of the partitioning membranes of the brain and the neck
      in head injury analysis through free-vibration analysis and transient analysis.
      In free-vibration analysis, the first five modal frequencies are calculated, and
      in transient analysis intracranial pressure and maximum shear stress in the brain
      are determined for a given occipital impact load.

PMID- 8857311
TI  - Adaptive motor unit action potential clustering using shape and temporal
      information.
AB  - An adaptive algorithm is described that groups motor unit action potentials
      (MUAPs), detected in a composite EMG signal during signal decomposition, and
      creates partial motor unit action potential trains (MUAPTs). Data-driven MUAP
      shape and motor unit firing-pattern based criteria are used to form the clusters.
      An algorithm for estimating MUAPT temporal parameters, which provides accurate
      estimates even for partially defined trains, is used to obtain firing-pattern
      information. No a priori knowledge is required regarding the number of clusters
      or the distribution of their template shapes. The clustering algorithm when
      applied to real concentric-needle detected MUAP data provides accurate and useful
      clustering results. Compared to a classical leader-based algorithm, it provides
      more robust performance, is better able to estimate the true number of motor
      units represented in a set of detected MUAPs, and obtains more complete and
      accurate MUAPTs.

PMID- 8857310
TI  - Resolving superimposed motor unit action potentials.
AB  - A new algorithm to resolve superimposed motor unit action potentials (MUAPs) is
      described, which uses a reduced search space and is based on the peel off
      approach. Knowledge specific to the problem domain, such as temporal
      relationships between and within motor unit action potential trains and MUAP
      energy information, is used to reduce the search space of motor units, possibly
      contributing to a superposition. The algorithm is tested using real
      electromyographic signals, and it demonstrates robust performance across the
      signals tested. For the signals tested, the average total resolution rate is 94%,
      the average correct resolution rate is 99.2% and the average error rate is 0.85%.

PMID- 8857312
TI  - Robust method for estimating motor unit firing-pattern statistics.
AB  - An error-filtered estimation (EFE) algorithm for estimating the mean and standard
      deviation of a set of time intervals between consecutive motor unit firing times
      (inter-pulse intervals (IPIs)) is described. As the input IPI data are filtered
      and only valid IPIs are used to estimate mean and standard deviation values, the
      EFE algorithm provides accurate estimates even when the data defining the train
      of motor unit firing times are only partially complete or have several erroneous
      firing times. The algorithm has been evaluated using both simulated and real
      motor unit firing time data, and has been found to provide accurate and unbiased
      mean and standard deviation estimates, even when up to 70% of the IPI data are
      incorrect.

PMID- 8857313
TI  - Adaptive estimation of QRS complex wave features of ECG signal by the Hermite
      model.
AB  - The most characteristic wave set in ECG signals is the QRS complex. Automatic
      procedures to classify the QRS are very useful in the diagnosis of cardiac
      dysfunctions. Early detection and classification of QRS changes are important in
      real-time monitoring. ECG data compression is also important for storage and data
      transmission. An Adaptive Hermite Model Estimation System (AHMES) is presented
      for on-line beat-to-beat estimation of the features that describe the QRS complex
      with the Hermite model. The AHMES is based on the multiple-input adaptive linear
      combiner, using as inputs the succession of the QRS complexes and the Hermite
      functions, where a procedure has been incorporated to adaptively estimate a width
      related parameter b. The system allows an efficient real-time parameter
      extraction for classification and data compression. The performance of the AHMES
      is compared with that of direct feature estimation, studying the improvement in
      signal-to-noise ratio. In addition, the effect of misalignment at the QRS mark is
      shown to become a neglecting low-pass effect. The results allow the conditions in
      which the AHMES improves the direct estimate to be established. The application
      is shown, for subsequent classification, of the AHMES in extracting the QRS
      features of an ECG signal with the bigeminy phenomena. Another application is
      highlighted that helps wide ectopic beats detection using the width parameter b.

PMID- 8857314
TI  - Monitoring set-up for selection of parameters for detection of hypoglycaemia in
      diabetic patients.
AB  - Recurrent severe hypoglycaemia is often an unsolved problem in diabetic patients
      under intensified insulin treatment. As no reliable long-term stable blood
      glucose sensor has yet been developed, registration of other body function
      changes could help to detect severe hypoglycaemia. A measuring system is
      described, capable on the one hand of recording EEG, heart rate, peripheral
      pulse, skin temperature, respiratory movements, skin impedance and arterial blood
      pressure, and capable of registering plasma glucose, counter-regulatory hormones,
      symptoms and cognitive performance under experimental conditions during
      hypoglycaemia, on the other. In a clinical study involving both insulin-induced
      hypoglycaemia in healthy subjects and insulin-dependent diabetic patients, the
      practical value and the character of changes of the recorded parameters are
      investigated. Currently insensitivity to hypoglycaemia, impracticability,
      complexity or susceptibility to artefacts make use of most parameters unsuitable
      for hypoglycaemia prevention. It is believed, however, that future efforts could
      result in indirect registration of hypoglycaemia, including a qualified
      combination of different parameters, individual adaptation in accordance with
      particular responses of individual patients, together with new measuring and
      sensor techniques.

PMID- 8857315
TI  - Description and validation of a technique for the removal of ECG contamination
      from diaphragmatic EMG signal.

PMID- 8857316
TI  - Standard algorithm for blood pressure measurement by sphygmo-oscillographic
      method.

PMID- 8857317
TI  - Optimalisation of the spot electrode array in impedance cardiography.

PMID- 8857318
TI  - Optimised method for locating reference markers in rontgen stereophotogrammetric
      analysis of orthopaedic radiographs.

PMID- 8857319
TI  - Reduction of motion artefacts during paediatric/infant apnoea monitoring.

PMID- 8857320
TI  - Monitoring rectal core temperature in marathon swimmers.

PMID- 8857321
TI  - Optical lever method for video-based micro-kinematic analysis.

PMID- 8857322
TI  - Obstructive symptoms in athletes: is it asthma and what to do about it?

PMID- 8857323
TI  - Value of preoperative spirometry to predict postoperative pulmonary
      complications.
AB  - In order to determine the incidence of postoperative pulmonary complications
      (POPC) and the value of preoperative spirometry to predict pulmonary
      complications after upper abdominal surgery, 24 women and 36 men (total 60
      patients) were studied prospectively (mean age 48 center dot 3 years). On the day
      before the operation and for 15 days after the operation, each patient's
      respiratory status was assessed by clinical examination, chest radiography,
      spirometry and blood gas analysis, and patients were monitored for pulmonary
      complications by a chest physician and a surgeon independently. In this study,
      postoperative pulmonary complications developed in 21 (35%) patients (pneumonia
      in 10 patients, bronchitis in nine patients, atelectasis in one patient,
      pulmonary embolism in one patient). Of 31 patients with abnormal preoperative
      spirometry, 14 (45 center dot 2%) patients showed complications, whereas among 29
      patients with normal preoperative spirometry, 7 (24 center dot 1%) patients
      showed complications (P <0 center dot 05). The incidence of POPC was higher in
      patients with advanced age, smoking, preoperative abnormal findings obtained from
      physical examination of the chest, higher ASA class and longer duration of
      operation. The sensitivity (0 center dot 76) and specificity (0 center dot 79) of
      abnormal preoperative findings obtained from physical examination to predict POPC
      were higher than abnormal preoperative spirometry (0 center dot 67 and 0 center
      dot 56 retrospectively). There was no significant difference between patients
      with and without pulmonary complications in regard to weight, serum albumin, type
      of incision, incidence of abnormal preoperative blood gases and duration of
      postoperative hospital stay. We conclude that POPC is still a serious cause of
      postoperative morbidity. Multiple risk factors include preoperative abnormal
      spirometry responsible for development of POPC. If used alone, spirometry has
      limited clinical value as a screening test to predict POPC after upper abdominal
      surgery.

PMID- 8857324
TI  - Clinical features of Stenotrophomonas maltophilia pneumonia in immunocompromised
      patients.
AB  - Between January 1988 and December 1992, 68 patients admitted to our Department of
      Internal Medicine with haematological malignancies or solid tumours showed
      colonization of the respiratory tract with Stenotrophomonas maltophilia. To
      characterize the significance of respiratory tract colonization by S.
      maltophilia, we retrospectively reviewed the medical records of the 68 patients
      colonized with this organism. Twenty-nine of these 68 patients developed
      pneumonia, with S. maltophilia being implicated in 10 cases. The majority of
      these 10 patients showed lobular infiltration on chest X-ray. Pleural effusion
      was observed in two (20%) of the 10 patients. All 68 strains of S. maltophilia
      were resistant to imipenem. Latamoxef was effective against 98 center dot 5% of
      strains, while minocycline was effective against 100% of strains. This report
      describes the clinical features of nosocomial S. maltophilia pneumonia in
      immunocompromised patients.

PMID- 8857325
TI  - Eosinophil peroxidase: a new serum marker of atopy and bronchial hyper
      responsiveness.
AB  - Do markers of eosinophil activation differ in their ability to detect subjects
      with atopy or bronchial hyper-responsiveness (BHR)? Comparisons of serum levels
      of eosinophil peroxidase (S-EPO), of eosinophil cationic protein (S-ECP) and the
      blood eosinophil count (B-Eos) have been made between 154 subjects aged 20-44
      years, participating in the European Community Respiratory Health Survey in
      Uppsala, Sweden. Subjects with atopy had significantly higher levels of S-EPO and
      S-ECP than those without atopy (P <0 center dot 001). Subjects with BHR had
      significantly higher levels of S-EPO (P <0 center dot 001) and B-Eos (P <0 center
      dot 01) than subjects without BHR. Persons reporting asthma-related symptoms had
      significantly higher levels of S-EPO and B-Eos than subjects without such
      symptoms (P <0 center dot 001 and P <0 center dot 01, respectively). Asthma
      symptom score correlated significantly to S-EPO (r = 0 center dot 26, P <0 center
      dot 01), S-ECP (r = 0 center dot 20, P <0 center dot 05) and B-Eos (r = 0 center
      dot 18, P <0 center dot 05). Finally, S-EPO was significantly more sensitive than
      S-ECP for detecting subjects with BHR (P <0 center dot 05) and significantly more
      sensitive than B-Eos for detecting both subjects with BHR and subjects with a
      combination of atopy and BHR (P <0 center dot 05). It is concluded that S-EPO is
      a promising marker with a higher sensitivity for BHR than S-ECP or B-Eos. Further
      studies are needed to define the value of S-EPO when following disease activity.

PMID- 8857326
TI  - Transdermal nicotine plus support in patients attending hospital with smoking
      related diseases: a placebo-controlled study.
AB  - BACKGROUND: Cessation rates in smokers attending special clinics or their General
      Practitioners can be increased by transdermal nicotine (TNS). This study assesses
      the efficacy of TNS as an adjunct to advice and support in helping patients
      attending hospital with smoking-related diseases to stop smoking. METHODS: In a
      double-blind, placebo-controlled, randomized manner, 234 inpatients and
      outpatients with smoking-related respiratory or cardiovascular disease, aged 18
      75 years, who were willing to try to stop smoking, were advised by their hospital
      doctor to stop smoking. This was reinforced by repeated advice and encouragement
      from the Smoking Cessation Counsellor initially and at 2, 4, 8 and 12 weeks,
      supplemented by a 24 h patch in adjusted doses over that period. Those not
      smoking at 12 weeks were followed up at 26 and 52 weeks. Self-reported complete
      abstinence from 12 to 52 weeks was validated by expired air carbon monoxide
      measurement at 12, 26 and 52 weeks. RESULTS: Twenty-four (21%) of 115 TNS
      patients were verified as non-smokers at 12, 26 and 52 weeks and claimed
      continued abstinence, compared with 17 (14%) of 119 in the placebo (P) group (P =
      0 center dot 15) -5% confidence limits for odds ratio of abstinence on TNS
      compared to P: 0 center dot 83, 3 center dot 37. Cessation was related to
      increasing age (P = 0 center dot 02) and lower Fagerstrom score (P = 0 center dot
      05). Minor skin reactions were more frequent in the TNS group (47% TNS; 34% P),
      as was nausea (12% TNS; 3% P). Severe skin reactions were rare (5% TNS; 4% P).
      CONCLUSION: The suggestion that TNS produces an increase of 50% in relative terms
      (7% absolute increase) in smoking cessation over placebo in this population of
      hospital patients is sufficiently strong to warrant a further study large enough
      to answer whether or not this result was due to chance.

PMID- 8857327
TI  - Recurrent respiratory papillomatosis with malignant transformation in a young
      adult.
AB  - The term 'papilloma' was first used by Mackenzie 100 years ago, who claimed that
      this was the most benign tumour of the larynx. Today papillomas are considered to
      be caused by the Human Papilloma Virus group (H.P.V.). The majority of patients
      suffering from this disease which is also referred to as 'recurrent respiratory
      papillomatosis' require multiple surgical operations for tumour removal.
      Malignant transformation of papillomas, which is a rare condition, is considered
      to occur mainly to irradiated patients. The following report describes the case
      of a male patient, with a history of vocal cord papillomas since his first year
      of age, who developed bronchial and pulmonary spread of the disease. He died at
      the age of 26 years because of squamous cell carcinoma which was related to the
      malignant transformation of the pulmonary papillomas.

PMID- 8857328
TI  - Cryptogenic organizing pneumonia in association with Sweet's syndrome.

PMID- 8857329
TI  - Cirrhosis of the liver, an exceptional cause of chylothorax: two cases.
AB  - Chylothorax, a condition featuring an infrequent form of pleural effusion, is
      generally caused by tumours or traumatism. Only about 1% of chylothorax cases are
      caused by cirrhosis of the liver. Two such cases are described in these case
      reports.

PMID- 8857330
TI  - Synergetic mechanisms in energy and signal transduction: photo oscillating proton
      transport in bacteriorhodopsin.
AB  - Receptor proteins, linked with G-proteins and effector proteins, which act in
      signal information and energy transduction are key elements in biochemical
      systems that dissipate energy and rely on maintenance of order. Until now they
      have not yet been considered as elements for synergetic mechanisms. This paper
      describes the synergetic mechanisms of the archaebacterial signal and energy
      receptor bacteriorhodopsin (bR), for which, recently, light induced oscillations
      have been experimentally demonstrated. A synergetic mechanisms for proton pumping
      by this protein is presented. An important precondition is the ability of the
      molecule to significantly reduce its entropy (i.e. to increase its order through
      export of entropy) during the photo cycle. This should be paralleled by a
      systematic and organized change of pK values along the proton transducting
      "channel". The interaction of occupied and vacant protonation sites at such
      energized amino acid chains gives rise to feedback loops leading to an
      autocatalytic mechanism of proton transfer which, in combination with
      nonlinearities at the membrane interfaces and a time delay during the proton back
      flux, provides a simplified mechanism for oscillative light induced proton
      pumping. The expected relevance of autocatalytic and synergetic processes as
      inbuilt mechanisms for energy conversion and signal processing and the
      maintenance of order is discussed.

PMID- 8857331
TI  - A simple model of recurrent epidemics.
AB  - A cellular automaton conceived as a simple model of disease spreading is
      investigated. We show that the steady-state of the model is described by a
      spatial organization of the infectious individuals on fronts and undamped
      temporal oscillations in the number of infectious individuals. This behaviour is
      observed both for a deterministic and a stochastic input of susceptible
      individuals, hence showing that recurrent epidemic behaviour can be persistent
      without any external forcing. The simplicity of the model suggests that such
      spatio--temporal behaviour can be obtained from nothing, but a direct
      transmission mechanism between nearest neighbors provided some mechanism for the
      introduction of new susceptible individuals, e.g., loss of immunity is present.

PMID- 8857332
TI  - Evaluation of feline leukemia virus control measures.
AB  - A susceptible-infected-recovered-susceptible (SIRS) model of the epidemiology of
      feline leukemia virus is formulated and analysed. The dynamics of the disease are
      dramatically different in no-risk, low-risk and high-risk subpopulations of
      asocial, free roaming, and multiple cat household cats. Among low risk (<1%
      prevalence) free roaming cats, the model predicts that an effective immunization
      rate of 4% year-1, or an effective removal rate of 8% year-1 are adequate to
      control the disease completely. Under higher risk (10% prevalence) conditions, an
      effective immunization rate of 23-72% year-1 or a removal rate of 69-145% year-1
      are required for control. At very high (30%) prevalence rates, even heroic
      measures may not suffice to substantially reduce disease prevalence: a
      vaccination rate of 100% year-1 even if attainable, would only slightly reduce
      disease prevalence from 30% to 29%. We conclude that the current estimated
      effective feline leukemia virus immunization rate of 11-19% of the general
      population is inadequate to provide herd immunity in the subpopulation of cats
      which are genuinely at risk of infection. A substantial increase in the
      vaccination rate and/or intensification of test and removal efforts in the at
      risk population would be required to attain an effective level of protection.

PMID- 8857333
TI  - On evolutive systems and the initial evolution of structure and function.
AB  - As an instrument for the study of the early stages of evolution, we introduce
      evolutive systems, defined as systems that have the capacity to evolve given
      appropriate conditions in their environment. They consist of building blocks
      (e.g. monomers) that are either stable or in steady supply, and of transient
      assemblies (e.g. polymers) that are entities of great variety, some of which are
      capable of function. Evolution leads to the accumulation of structure within the
      transient assemblies during repeated cycles of disintegration (partial or total)
      and reassembly, on account of the selective advantages associated with transient
      assembly functions. Transient assemblies must be either inherently unstable or
      subject to disintegration by agents in their environment. Evolutive systems must
      have access to a negentropy input in the form of energy in packets larger than
      typical thermal energies. Reproduction, although not a prerequisite, greatly
      affects the capacity of evolutive systems to evolve, and thus can be expected to
      appear in an evolutive system if at all possible. Similarly, functions that
      require the expenditure of negentropy (for example mobility, breathing,
      circulation, sensing, communicating, etc.) are not prerequisites for evolution,
      but can be expected to become established in evolutive systems during evolution
      through the selective advantages that they confer. A computer-based evolutive
      automaton is used to explore possible evolutionary scenarios. In the presence of
      spatial and temporal inhomogeneities, one can construct a multitude of
      evolutionary scenarios through which various functions, such as the operation of
      genetic code, can become established within the evolutive automaton. This variety
      of possible evolutionary scenarios is all the more remarkable because the
      automaton does not include many important physical processes that would be
      present in a real system and would greatly multiply the number of possible
      evolutionary mechanisms and scenarios. Some evolutionary mechanisms are based on
      survival related selection, while others are based on generation related
      selection. Previously explored scenarios for the initiation of life have been
      based mostly on generation related selection. In this paper, we give particular
      emphasis to survival related selection which is more general in that it does
      apply to structures and functions related to reproduction but, unlike generation
      related selection, it is not limited to them. Some of the most basic features of
      terrestrial living systems can be seen either as prerequisite features of an
      evolutive system (such as the mortality of living organisms, instability of
      biological polymers, imperfect reproduction caused by mutations, and the need for
      a negentropy input) or as features that one can reasonably expect to become
      established in an evolutive system (such as reproduction and the multitude of
      living functions that require expenditure of negentropy). This suggests the
      possibility that an independent definition of living systems may not be necessary
      if features of living systems substantially overlap with features that one may
      expect to find in evolutive systems.

PMID- 8857334
TI  - Bullous pemphigoid and multiple sclerosis: a report of three cases and review of
      the literature.
AB  - Three patients with longstanding multiple sclerosis (MS) who developed bullous
      pemphigoid (BP) are reported. All patients had immunological features of typical
      BP as determined by immunofluorescence and Western immunoblotting studies. The
      clinical features, however, differed from those observed in typical BP. In two
      the BP started near an indwelling catheter and two had striking involvement of
      the soles. None of our patients, or a further nine cases reported in the
      literature, had mucous membrane involvement. In MS patients BP appears to develop
      at a younger age. Multiple drugs were taken by the MS patients; these, however,
      appear not to play a role in triggering their BP. The course of BP in patients
      with MS is moderate, although the majority require systemic treatment.

PMID- 8857335
TI  - Comparative study of autoantigens for various bullous skin diseases by
      immunoblotting using different dermo-epidermal separation techniques.
AB  - We investigated the reactivity of pemphigus vulgaris (PV), pemphigus vegetans,
      pemphigus foliaceus (Pf), Brazilian Pf, bullous pemphigoid (BP), and
      epidermolysis bullosa acquisita (EBA) sera with an immunoblot analysis using
      human epidermal and dermal extracts as a source of antigen. To obtain epidermal
      and dermal extracts three different dermo-epidermal separation methods were used:
      namely, ethylenediaminetetraacetic acid (EDTA) separation, heat separation, and
      dispase separation. All the 15 PV and the seven pemphigus vegetans sera
      demonstrated a 130-kDa PV antigen in epidermal extracts obtained by all the three
      methods. Furthermore, three PV sera also showed a 160-kDa Pf antigen, desmoglein.
      Ten of 14 Pf sera and six of 15 Brazilian Pf sera reacted with desmoglein in the
      same pattern in all the three epidermal extracts. Fifteen of the 22 BP sera
      showed reactivity with 230-kDa BP antigen in the same pattern in all the three
      epidermal extracts, whereas 14 BP sera detected the 180-kDa BP antigen in
      extracts of EDTA- and heat-separated epidermis but not in dispase-separated
      epidermal extract. Dermal extracts were obtained by EDTA- and heat-separated
      dermis, and all six EBA sera labelled a 290-kDa EBA antigen in both samples.
      These results suggest that heat-separated skin is as useful as EDTA-separated
      skin for detecting various autoantigens, but heat separation is preferable
      because the preparation time is shorter.

PMID- 8857336
TI  - Mitozantrone-induced onycholysis. A series of five cases.
AB  - The anthracenedione cytotoxic agent, mitozantrone, has a well-established place
      in the treatment of acute leukaemia, lymphoma, breast carcinoma and other
      malignant tumours. In general it is well tolerated apart from myelosuppression
      and dose-related cardiotoxicity. Alopecia is a common side-effect with
      mitozantrone but otherwise the skin and its appendages are rarely affected. We
      present five cases of mitozantrone-induced onycholysis.

PMID- 8857337
TI  - Neuropeptides in the skin of patients with atopic dermatitis.
AB  - There is increasing evidence that neuropeptides may be involved in the
      pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide
      distribution in the skin of patients with AD differs from normal controls. The
      distribution and density of several neuropeptides were examined in lesional and
      non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using
      indirect immunofluorescence and image analysis. Cholinergic innervation was
      studied using cholinesterase histochemistry. Staining with the general neuronal
      marker protein gene product 9 x 5 showed a subepidermal network of nerves with
      fibres penetrating the epidermis, and nerves around blood vessels, sweat glands
      and hair follicles. Image analysis of nerves around sweat glands showed a
      significantly higher nerve density in non-lesional compared with both normal
      controls and lesional skin (P < 0.05); lesional compared with control skin showed
      no significant difference. In the epidermis the density of nerves was not
      significantly greater in non-lesional compared with lesional skin and controls.
      Calcitonin gene-related peptide immunoreactivity was similar in all subjects
      except in three of the AD patients, where more nerves appeared to penetrate the
      epidermis. Substance P immunoreactivity in the papillary dermis was seen in all
      AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y
      staining were similar in all groups. Acetylcholinesterase-positive nerves were
      found around sweat glands in all subjects, the staining being greatest in non
      lesional and least in lesional skin. Occasional nerves were seen in the papillary
      dermis in lesional skin of two out of the four patients. We have demonstrated
      quantitative differences in nerve growth in clinically normal skin of AD
      patients, and altered cutaneous neuropeptide expression in these patients which
      may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has
      not been fully established but it is believed that there is a complex interaction
      between genetic susceptibility, precipitating environmental factors and
      disordered immune responsiveness. There is increasing evidence that neuropeptides
      may be involved in the pathogenesis of AD. Exacerbations of the disease can be
      provoked by stress, scratching and sweating which may be the result of neurogenic
      inflammation. One of the first features of an exacerbation is flushing of the
      affected skin and pruritus. Several neuropeptides that have been identified in
      human skin are potent inducers of vasodilation and may induce pruritus. Substance
      P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal
      polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and
      CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a
      competitive antagonist of SP, has been shown to inhibit immediate and delayed
      type hypersensitivity reactions. Part of these responses may be due to release of
      histamine and indeed elevated concentrations of histamine have been found in vivo
      in the skin and plasma of patients with AD. In this study the distribution and
      density of several neuropeptides were examined in lesional and nonlesional skin
      of AD patients and in normal controls using indirect immunofluorescence and image
      analysis. Cholinergic innervation was studied using cholinesterase
      histochemistry. Because many afferent fibres do not express CGRP or SP, the
      general neuronal marker protein gene product (PGP 9 x 5) was used to assess the
      overall nerve supply to the skin.

PMID- 8857338
TI  - Serum sickness-like illness following streptokinase therapy. A case report.
AB  - We report a patient who developed a serum sickness-like illness characterized by
      fever, arthritis, haematuria and a purpuric eruption 7 days following
      streptokinase therapy for myocardial infarction. Blood tests demonstrated
      increased circulating immune complexes. The skin involvement resulted in
      extensive, painful cutaneous infarction with secondary bacterial infection. Serum
      sickness is an uncommon but recognized complication of streptokinase therapy.

PMID- 8857339
TI  - Generalized endemic Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is a multicentric neoplasm thought to arise from both
      vascular and lymphatic endothelium. It is subdivided into four main categories on
      the basis of clinical features, course and prognosis. We report a 54-year-old
      Afro-Caribbean male, living in the UK for the past 26 years, with classic
      features of generalized endemic KS. Because he has never lived on the African
      continent, the role of genetic rather than environmental factors is favoured in
      the aetiology of KS in this individual. This disorder is rarely seen in Afro
      Caribbeans living in the UK, who have never actually lived in Africa.

PMID- 8857340
TI  - Multiple dermatofibromas in a patient with HIV infection.
AB  - We report the case of a 26-year-old man with haemophilia B and human
      immunodeficiency virus infection (HIV) who presented with a short history of
      multiple dermatofibromas. He also had troublesome psoriasis for which he was
      receiving acitretin with UVB therapy and had recently discontinued low-dose daily
      prednisolone for associated arthropathy. Multiple dermatofibromas are rare and
      have been reported previously in association with autoimmune disease, especially
      in individuals receiving immunosuppressive therapy. We believe this to be the
      first report of multiple dermatofibromas in an individual with advanced HIV
      infection and propose that it may be related to his viral-mediated
      immunodeficiency, possibly augmented by UVB and systemic corticosteroid therapy.

PMID- 8857341
TI  - Reticulate acropigmentation of Dohi.
AB  - Two cases of reticulate acropigmentation of Dohi are reported, both patients
      demonstrating the typical features of this disorder. Reticulate acropigmentation
      of Dohi (dyschromatosis symmetrica hereditaria or symmetrical dyschromatosis of
      the extremities) is characterized by pigmented and depigmented macules mixed in a
      reticulate pattern on the extremities. It was first described in 12 patients from
      Japan, where it appears to be a well-established condition. Patients have been
      reported from Europe and a family from India has recently been described. We
      report two cases of reticulate acropigmentation of Dohi occurring in an Afro
      Caribbean and an Indian patient, in order to alert clinicians to the possibility
      that this disorder may present in the UK.

PMID- 8857342
TI  - Cutaneous cryptococcosis and Kaposi's sarcoma occurring in the same lesions in a
      patient with the acquired immunodeficiency syndrome.
AB  - A 34-year-old woman presented with a history of fever, malaise and skin lesions.
      A diagnosis of Kaposi's sarcoma and acquired immunodeficiency syndrome (AIDS) was
      established, and in addition, the skin lesion which was biopsied also
      demonstrated cryptococcal infection. Disseminated cryptococcosis was later
      confirmed and the disease ran a florid course. The co-existence of different
      diseases within the same lesion is a feature of human immunodeficiency virus
      (HIV) infection, this being the third documented case of simultaneous Kaposi's
      sarcoma and cutaneous cryptococcosis occurring at the same site in a patient with
      AIDS. The nature of this co-existence is discussed with reference to the
      pathogenesis of Kaposi's sarcoma.

PMID- 8857343
TI  - Penile basal cell carcinoma with eccrine differentiation.
AB  - Basal cell carcinoma (BCC) is rare on the penis. There have been only 17 cases of
      penile BCC reported in the literature. Eccrine differentiation may not be
      uncommon in BCC but has not been reported in penile BCC. We report here a 75-year
      old man with multiple penile BCC with histological features of eccrine
      differentiation. A brief review of the literature is included. Basal cell
      carcinoma (BCC) is the most commonly diagnosed malignant skin tumour; it probably
      originates from pluripotential cells in the epidermis or hair follicle. More than
      90% of BCCs are located on the head or neck, and its occurrence on the penis is
      rare. Seventeen cases of penile BCC have been reported in the literature.

PMID- 8857344
TI  - Pyoderma gangrenosum complicating hysterectomy for fibroids.
AB  - Pyoderma gangrenosum is a destructive, non-infective ulceration of the skin. The
      case presented illustrates a rare but important presentation in a patient
      following a total abdominal hysterectomy and bilaterial salpingo-oophorectomy
      (TAH and BSO).

PMID- 8857345
TI  - Acquired localized elastolysis associated with varicose veins.
AB  - Localized elastolysis refers to a group of heterogeneous conditions which
      includes cutis laxa. We report a form of localized and non-inflammatory
      elastolysis evocative of cutis laxa, localized to the anteromedial aspect of the
      left thigh and knee, acquired at the age of 8 years and associated with
      unilateral adjacent venous dilatations appearing at the age of 39 years. Our case
      is clinically and ultrastructurally compatible with cutis laxa. Localized forms
      of cutis laxa not preceded by inflammation are exceptional; localization on the
      leg has never been described. This clinical form of elastolysis calls into
      question the classification of acquired elastolysis. The adjacent varicose veins
      also raise the question of the risk of subcutaneous damage in this condition.

PMID- 8857346
TI  - Pyoderma gangrenosum associated with acne conglobata.
AB  - We report a 16-year-old male in whom pyoderma gangrenosum appeared in conjunction
      with acne conglobata. The patient also developed a seronegative
      spondyloarthropathy that was the main presenting complaint. There was no evidence
      of inflammatory bowel disease. Treatment with isotretinoin was successful. Both
      acne and pyoderma lesions healed and the articular symptoms improved. The present
      case, together with other reports in the literature show that acne conglobata
      must be included in the list of possible associations of pyoderma gangrenosum. We
      also comment on acne arthritis, a relatively frequent phenomenon, although still
      not generally known, in acne conglobata.

PMID- 8857347
TI  - 'Naevophobia'.
AB  - In recent years there has been intensive media interest in pigmented lesions and
      several skin cancer prevention/early detection campaigns. Pigmented lesions may
      cause great anxiety, although patients are usually reassured once their moles
      have been examined by a dermatologist. We describe a case in which a young man
      with multiple pigmented naevi attempted to remove all the lesions himself. This
      self-mutilation occurred despite his having attended a dermatology clinic.

PMID- 8857348
TI  - Sarcoidosis presenting as erythema annulare centrifugum.
AB  - Erythema annulare centrifugum (EAC), a disease belonging to the poorly
      characterized category of 'figurate erythemas', has been associated with a
      variety of conditions, such as connective tissue diseases, infections, neoplasms
      and drug reactions. Here we report a case of EAC associated with sarcoidosis, the
      first case in the literature to our knowledge. EAC was the sole sign of the
      granulomatous disease process, which was diagnosed by means of appropriate
      investigations only after the patient reported the sudden resolution of a long
      standing sensitization to perfumes and parabens. Steroid treatment for
      sarcoidosis improved the patient's condition, and restored the allergic response
      to these substances.

PMID- 8857349
TI  - Verruciform xanthoma of the penis with acantholytic cells.
AB  - Verucciform xanthoma is an unusual lesion characterized by verrucous epithelial
      proliferation accompanied by a prominent replacement of the dermal papillae with
      foamy histiocytes. We describe a case of verruciform xanthoma on the glans penis.
      The most striking histopathological finding was the presence of numerous
      acantholytic cells in the upper layers of the epithelium. We discuss the
      differential diagnosis with other acantholytic disorders of the genital area and
      conclude that our findings can be interpreted as an additional example of
      incidental acantholysis.

PMID- 8857350
TI  - Gymnasium acne.

PMID- 8857351
TI  - Piezoelectricity of biopolymers.
AB  - The piezoelectricity of semicrystalline biopolymers was first discovered for wood
      and bone in the 1950's. Piezoelectric properties have since been investigated for
      a number of biological substances, including polysaccharides, proteins and
      deoxyribonucleates. The shear piezoelectric constants -d14 = d25 were determined
      for their oriented structures with a uniaxial symmetry Dinfinity. From studies of
      synthetic polypeptides and optically active polymers, it was concluded that the
      origin of piezoelectricity lies in the internal rotation of dipoles such as CONH.
      Values of d14 = -10 pC/N were determined for highly elongated films of poly-L
      lactic acid, optically active and biodegradable. The implantation of this polymer
      induced the growth of bone, possibly because ionic current caused by
      piezoelectric polarization stimulated the activity of bone cells. Submicron-thick
      polyurea films were prepared by evaporating diisocyanate and diamine monomers in
      vacuum. After poling, the films exhibited pyro- and piezoelectric effects. The
      tensile piezoelectric constant d31 = 10 pC/N persisting up to 200 degrees C was
      also observed for aliphatic polyurea films.

PMID- 8857352
TI  - Nonlinear viscoelasticity and the thrombelastograph: 1. Studies on bovine plasma
      clots.
AB  - To study the possible role of nonlinear viscoelastic effects in the
      thrombelastograph (TEG), clotting of bovine plasma was studied by both
      thrombelastography and with a controlled strain rheometer. Clot rheology is
      dominated by elastic effects at frequencies of interest. There is a well-defined
      regime of linear elasticity for strains less than around 2%, while at larger
      strains the clots show significant strain hardening. Oscillatory shear applied
      during clotting has little effect on the resulting clot provided that the strain
      is less than 2%, but leads to substantial weakening of clots formed at larger
      strains. The TEG operates within the regime of nonlinear elasticity,
      significantly obscuring the interpretation of TEG amplitude in terms of an
      elastic modulus. Comparing the results of standard TEG experiments with those
      conducted with a modified TEG, having no oscillation during clotting, shows that
      deformation during standard thrombelastography leads to weaker clots than are
      produced under quiescent conditions.

PMID- 8857353
TI  - Recording of unexpectedly high frequency vibrations of blood vessel walls in
      experimental arteriovenous fistulae of rabbits using a laser vibrometer.
AB  - Because arteriovenous fistulae are associated with a palpable thrill and an
      audible murmur, the vibrational activity of the blood vessel walls about
      experimental arteriovenous fistulae in rabbits was investigated using, for the
      first time, a high-resolution laser vibrometer. Frequencies of mural vibrations
      up to 2200 Hz were recorded at different sites about the fistulae. The
      relationship of this vibratory activity of blood vessel walls to physiological
      and pathological conditions warrants further investigation.

PMID- 8857354
TI  - The effects of temperature on the filtration of diluted blood through 3 mu m and
      5 mu m filters.
AB  - The effect of temperature on the flow of diluted blood [Hct = 0.21], through 5 mu
      m Nuclepore filters, is described by the Arrhenius equation with an energy of
      activation of 27.7 kJ/mol. Plasma, diluted with PBS, is almost three times less
      sensitive to temperature, with an energy of activation of 9.8 kJ/mol, while red
      cells are of intermediate sensitivity, with an energy of activation of 14.7
      kJ/mol. The most sensitive elements to changes in temperature are leukocytes,
      with energies of activation of 31 kJ/mol and 35 kJ/mol for fast-flowing
      leukocytes (granulocytes and lymphocytes) and slow-flowing leukocytes (monocytes)
      respectively. Hence, the major determinants of the decline in filterability of
      blood through micropore filters are the leukocytes. This effect is compounded
      when blood is kept for 10 minutes or more at 10 degrees C due to activation of
      granulocytes, which leads to permanent pore blocking when the affected blood is
      filtered at room temperature. The combination of increased passage time of
      leukocytes through peripheral areas at abnormally low temperatures and subsequent
      activation might influence the flow of blood in non-affected tissues. The effect
      of temperature on the filterability of red blood cells through 3 mu m filters is
      not described by the Arrhenius equation and the deviations are seen as a gradual
      change of slope rather than a sharp break between two straight lines. The data
      are consistent with a gradual shift in rate limiting step away from the entry
      event into pores, which dominates at low temperature but becomes progressively
      less important at elevated temperatures. The changing parameter is probably the
      volume of the red cell, which is less important when flow is measured through 5
      mu m pores.

PMID- 8857355
TI  - Flow-pressure drop measurement and calculation in a tapered femoral artery of a
      dog.
AB  - This study describes the in vivo measurement of pressure drop and flow during the
      cardiac cycle in the femoral artery of a dog, and the computer simulation of the
      experiment based on the use of the measured flow, vessel dimensions and blood
      viscosity. In view of the experimental uncertainty in obtaining the accurate
      velocity profile at the wall region, the velocity pulse at the center was
      measured and numerical calculations were performed for the center line
      instantaneous velocity and within the two limits of spatial distribution of inlet
      flow conditions: uniform and parabolic. Temporal and spatial variations of flow
      parameters, i.e., velocity profile, shear rate, non-Newtonian viscosity, wall
      shear stress, and pressure drop were calculated. There existed both positive and
      negative shear rates during a pulse cycle, i.e., the arterial wall experiences
      zero shear three times during a cardiac cycle. For the parabolic inlet condition,
      the taper of the artery not only increased the magnitude of the positive and
      negative shear rates, but caused a steep gradient in shear rate, a phenomenon
      which in turn affects wall shear stress and pressure. In contrast, for the
      uniform inlet condition, the flow through the tapered artery was predominantly
      the developing type, which resulted in reduction in magnitude of wall shear rate
      along the axial direction.

PMID- 8857356
TI  - Does Michigan have a shortage or a surplus?

PMID- 8857357
TI  - Federal labor laws. Are you in compliance?

PMID- 8857358
TI  - Outcomes measurement. A review of Michigan initiatives.

PMID- 8857359
TI  - MSMS task force explores alternatives.

PMID- 8857360
TI  - Thomas L. Haynes, MD. Making a small dent in the big problem of addiction.

PMID- 8857361
TI  - Rabies. New threats loom in Michigan.

PMID- 8857362
TI  - Formulating a functional model of attention deficit hyperactivity disorder for
      the practicing speech-language pathologist.
AB  - Speech-language pathologists need to embrace new models of service delivery if
      their work with children having ADHD is to be successful. Old models that are
      oriented toward deficits have proven to be ineffective, but application of a
      systems-theory approach from the social sciences to ADHD, together with support
      from recent educational research, provides a contextually-related model of
      service delivery. This model is discussed in terms of three major issues-
      identifying and describing students with ADHD, helping them overcome their
      problems, and meeting the needs of their teachers and parents--and how it may
      guide more effective assessment and intervention of ADHD students in educational
      settings.

PMID- 8857363
TI  - Intervention strategies for students with ADHD: creating a holistic approach.
AB  - An overview of therapy approaches commonly used by speech-language pathologists
      with students having ADHD and their primary intervention responsibilities with
      these students is presented. Several strategies for establishing the kinds of
      learning contexts necessary for success are described, which emphasize the
      importance of empowering students in meaningful and relevant contexts. Five major
      intervention strategies for working with ADHD students are reviewed briefly-
      modifying learning environments, pharmacological therapy, behavioral management,
      cognitive-behavior modification, and classroom academic management--and detailed
      references for each are provided.

PMID- 8857364
TI  - Treatment of attention deficit hyperactivity disorder: a multi-modal model for
      schools.
AB  - Treatment of ADHD in schools has received comparatively little attention, even
      though children spend more time in school than in most other structured
      environments and have their most consistent, extensive contact with a variety of
      trained professionals there. Because schools could play a strategic role in
      treating ADHD children, a multi-modal treatment model for children with ADHD in
      school settings is presented, and logistic factors likely to increase its
      effective implementation are reviewed. Then, a functional approach to the
      assessment and treatment of ADHD that focuses on identifying individual-specific
      deficiencies and environmental factors that may prevent these children from
      performing appropriate behavior is discussed.

PMID- 8857365
TI  - Attaining, sustaining, and focusing attention: intervention for children with
      ADHD.
AB  - An alternative intervention approach for children with ADHD, a "situational
      discourse-semantic model," is described. This approach examines the interactions
      between environmental factors and a student with ADHD and determines the roles of
      these factors in the establishment of a student's "deficit." Once this is
      accomplished, selected factors can be manipulated to increase the student's
      ability to attain the attention needed for academic tasks, to sustain such
      attention during academic tasks, and then to focus attention on key task elements
      so that a more effective environment for learning and communication is achieved.
      The application of the model's principles is illustrated through case study
      descriptions of therapy interactions with a young boy with ADHD.

PMID- 8857366
TI  - Educating every teacher, every year: the public schools and parents of children
      with ADHD.
AB  - This article reports findings from interviews with 20 parents about their
      experiences in obtaining services for their ADHD children in school systems.
      Grounded theory methods were used to analyze data at both individual and
      organizational levels. Parents saw school personnel as varying widely in their
      knowledge about ADHD and their acceptance of its associated problems. At the
      individual level, parents felt that they had to educate a succession of different
      school personnel each year. At the organizational level, they had to work
      actively to obtain continuity of services for their children from year to year
      and school to school, but for most parents, this outcome was desired more often
      than realized. On the whole, parents perceived schools as having failed to
      respond adequately to their children's educational needs.

PMID- 8857367
TI  - Waiting for a match: the future of psychosocial treatment for alcohol problems.

PMID- 8857368
TI  - Preventing fetal alcohol syndrome: where are we now?

PMID- 8857369
TI  - Alcohol policy and the public good: a good public debate.

PMID- 8857370
TI  - Alcohol misuse and juvenile offending in adolescence.
AB  - The associations between alcohol misuse and juvenile offending during the period
      from 15 to 16 years of age were studied in a birth cohort of New Zealand
      adolescents. This analysis showed that young people who misused alcohol had
      significantly (p <0.001) higher rates of both violent and property offences.
      These associations were similar for males and females. Further analysis suggested
      that a substantial component of the association between alcohol misuse and
      juvenile offending arose from shared risk factors that were common to both
      outcomes. These risk factors included measures of family social background,
      family and parental characteristics, individual characteristics and adolescent
      peer affiliations. After adjustment for antecedent risk factors there was no
      significant association between alcohol misuse and odds of property offences.
      However, young people who abused alcohol had odds of violent offending that were
      3.2 times (p< 0.001) the odds of those offences for young people who did not
      misuse alcohol. It is concluded: (a) that a large component of the association
      between alcohol misuse and juvenile offending arises because of the effects of
      shared risk factors that are associated with both outcomes; (b) none the less,
      the unexplained association between alcohol misuse and violent offending may
      suggest the presence of a direct cause and effect association in which adolescent
      alcohol misuse is associated with increased risks of violent offending.

PMID- 8857371
TI  - Comments on Fergusson et al.'s "Alcohol misuse and juvenile offending in
      adolescence".

PMID- 8857372
TI  - Explaining the link between problem drinking and delinquency.

PMID- 8857373
TI  - Significant connections.

PMID- 8857374
TI  - 'Unraveling juvenile delinquency' revisited--cohort studies at risk.

PMID- 8857375
TI  - The substance use-delinquency nexus.

PMID- 8857376
TI  - Alcohol misuse and juvenile offending in adolescence: a response to the
      commentaries.

PMID- 8857377
TI  - Places and patterns of drug use in the Scottish dance scene.
AB  - Interviews were conducted with 135 participants in the Glasgow dance (rave)
      scene. Drug use in this group was varied and not merely restricted to drugs
      associated with dance events, such as MDMA (Ecstasy). The setting in which each
      drug was used varied greatly. Amphetamine, nitrites and Ecstasy were the drugs
      most commonly used at dance events. Pharmaceuticals were least likely to be used
      in such settings. However, some drugs, such as Temazepam, were sometimes used
      prior to or after attending rave events. It is suggested that dance drug users
      are polydrug users who use drugs in a setting specific fashion. As such it would
      be wrong to classify such users solely on the grounds of their very visible
      behaviour in the public arena (at dance events). Other forms of substance use
      engaged in by this group may have a greater potential for harm than that seen at
      raves. The implications of these findings are discussed.

PMID- 8857378
TI  - Associations between drug use and behavioral repertoire in urban youths.
AB  - Converging with psycho-social research findings, animal and human laboratory
      studies indicate that behavioral alternatives are important determinants of drug
      taking. To investigate associations between how early adolescents spend their
      time, i.e. their behavioral repertoire and drug use (use of marijuana,
      crack/cocaine or inhalants), we analyzed data from an epidemiological sample of
      1516 urban middle-school students who had completed private interviews in spring
      1993. The interview included a 36-item questionnaire to assess how frequently the
      youth engaged in different activities; history of drug-taking was assessed
      separately. Multiple logistic regression was used to estimate associations
      between drug use and each of seven behavioral domains as well as sex, age and
      racial-ethnic status. Youths spending a great deal of time working for pay and
      assuming other adult-like roles were more likely to have initiated drug use
      (estimated odds ratio, OR = 3.49; p = 0.002). Those who spent much time in
      religious activities were less likely (OR = 0.2, p <0.001). An exploratory search
      for interactions disclosed other associations that merit attention in future
      research. These results corroborate evidence on the potential etiological
      significance of behavioral repertoire in relation to risk of drug use.

PMID- 8857379
TI  - Development of the cocaine relapse interview: an initial report.
AB  - Although fine-grained analyses of circumstances surrounding relapses have been
      conducted with alcoholics, smokers and opiate users, there is comparatively
      little information about the relapse process in cocaine abusers. The Cocaine
      Relapse Interview (CRI) is a structured interview that gathers information on the
      onset, course and termination of cocaine relapse episodes. This article describes
      the development of the CRI and presents initial data on its reliability and
      validity. Sections of the CRI assess experiences on the day of the relapse,
      experiences during the week prior to the relapse, attributions for the relapse,
      experiences following initial use of cocaine and factors in terminating the
      relapse. Most of the subscales in each section of the CRI had adequate internal
      consistency and test-retest reliabilities. Validity studies indicated that most
      of the subscales that assess experiences prior to relapse differentiated
      relapsers from two control groups of non-relapsers, and that several subscales
      and individual items from the sections that assess experiences following initial
      use and factors in termination differentiated "lapsers" from "relapsers".
      Limitations of the CRI and recommendations for its use were also discussed.

PMID- 8857380
TI  - Benzodiazepines in primary health care: a survey of general practitioners
      prescribing patterns.
AB  - This paper presents the results of a survey carried out to investigate the
      benzodiazepine (BZD) prescribing patterns of the general practitioners (GP) in
      the catchment area of a Drug Dependence Unit located in a general hospital in
      Mataro (Barcelona, Spain). The aims of the survey were: (i) to obtain descriptive
      information on the knowledge of the GPs about BZD and its potential for
      dependence; (ii) to study the frequency of their prescribing; and (iii) to
      examine different factors linked to their prescribing. The study was carried out
      using a combination of a personal interview and a self-administered
      questionnaire. A total of 68 doctors (88.3%) completed the questionnaire. The
      results show that the GPs have, in general, correct knowledge about the
      therapeutic indications for BZD prescribing, but are far less aware of their
      potential to induce dependence and how to manage withdrawal. The rate of
      prescribing seems to be high. Furthermore, the results of the external check of
      validity point out that doctors tend to underestimate the number of
      prescriptions. The majority of GPs express the need for alternative resources to
      BZD prescribing. No significant associations have been found between doctor's
      characteristics, such as postgraduate training and type of practice, and their
      knowledge about BZD and frequency of their prescribing. In our view, a more
      accurate knowledge about BZD and alternatives to its use, both factors closely
      linked to training, together with the availability of non-pharmacological
      resources, are likely to improve the quality of doctors prescribing habits, thus
      preventing risks such as dependence of BZD.

PMID- 8857381
TI  - Selection bias in national surveys due to screening: implications from a county
      general population survey.
AB  - National alcohol surveys using face-to-face interviews, such as the US 1988
      National Health Interview Survey Alcohol Supplement and the 1990 US National
      Alcohol Survey, for reasons of efficiency often use screener items to identify
      individuals who are likely to have experienced alcohol-related problems and only
      those individuals are chosen to respond to a list of alcohol-related problem
      questions. The consequence of screening is that only a subset of the current
      drinkers have complete data on such items. This paper examines the bias
      introduced by the exclusion of cases with incomplete information due to
      screening. Data from a regional general population survey were used to
      investigate possible bias due to screening because it included the screening
      questions used in NHIS and NAS but did not screen on those items. Risk curves and
      estimated probabilities from logistic regressions of three alcohol dependence
      symptom items and two problem indices were compared by gender across three
      subsamples: (1) all current drinkers (without screening); (2) those who passed
      the screener item for the NHIS and (3); the NAS, respectively. Results indicate
      that the effect of the screener items on the estimated prevalence of the measures
      concerned are minimal, supporting the practice, judiciously applied, when greater
      survey efficiency is required.

PMID- 8857382
TI  - Alcohol and sexual victimization: a longitudinal study of Norwegian girls.
AB  - In a study of sexual victimization and alcohol consumption, a population sample
      of Norwegian adolescents from the Oslo area was followed-up through five data
      collections over a 6-year time span. By means of generalized structural equation
      modeling, alcohol-related predictors and consequences of sexual assaults were
      investigated; 17% of the girls reported that they had been sexually assaulted at
      some time: 7% in childhood, 6% in early adolescence (13-16 years) and 4% in late
      adolescence (17-19 years). Only 1% of the boys reported having been sexually
      victimized. Female childhood sex victims reported increased alcohol consumption
      from their mid-teens, with dramatic increase in alcohol-related problems (using
      DSM-III-R criteria) at the end of their teens. However, the analyses showed that
      alcohol consumption was not influenced by childhood sexual abuse when parental
      use of tobacco and alcohol and normative standards imparted to their children
      were taken into consideration as confounding variables. There was, on the other
      hand, a strong effect on alcohol problems. Thus, the victims of childhood sexual
      abuse seem to be at high risk for alcohol abuse and dependency. Further, early
      alcohol debut and high alcohol consumption combined with permissive parental
      norms increased the risk of sexual assault in early adolescence. The girls who
      were assaulted in early adolescence also reported a high number of sexual
      partners and early intercourse debut. There was no increase in subsequent alcohol
      consumption after assaults in this group. Late adolescent victims did not report
      increased alcohol consumption either prior to or after the assault.

PMID- 8857383
TI  - The latent dimensionality of DIS/DSM-III-R nicotine dependence: exploratory
      analyses.
AB  - Decisions on DSM-IV criteria for alcohol dependence were based in part on latent
      structure analyses of field survey data on alcohol problems. Analogously, to
      investigate the latent structure of nicotine dependence in an epidemiological
      sample, we carried out a dichotomous item factor analysis of DSM-III-R symptom
      data gathered from 394 young adults who reported a history of sustained daily
      smoking. Smokers and their dependence symptoms were identified by means of the
      NIMH Diagnostic Interview Schedule version III revised, administered to a random
      sample of 1007 21-30-year-olds who were members of a health maintenance
      organization in the Detroit area. Comparing different latent structure models
      using LISCOMP software with bootstrap re-sampling, followed by multiple logistic
      regression, we found that a two-factor model indicating a 'general dependence'
      and a 'failed cessation' dimension best accounted for the observed data. Current
      smoking status (persistent vs. past smoking) was associated with the two factors
      independently. Replication and additional research on construct, discriminant and
      convergent validity are needed.

PMID- 8857385
TI  - Shades of grey: some observations on Sobell & Sobell's "Controlled drinking after
      25 years: how important was the great debate?".

PMID- 8857384
TI  - Alcohol outlet policies and practices concerning sales to underage people.
AB  - Little is known about the relationship between alcohol outlet policies and
      practices in the United States and the likelihood that outlets will sell
      alcoholic beverages to persons under the legal drinking age. This study assessed
      the prevalence of such outlet-level policies and practices, and analyzed the
      relationships between outlet variables and outlets' actual propensity to sell
      alcoholic beverages to youth. The sample consisted of all outlets licensed for
      off-premise and a 40% random sample of outlets licensed for on-premise sale of
      alcoholic beverages in 15 small to medium-sized communities in Minnesota and
      Wisconsin (USA). Data on outlet characteristics, policies and practices were
      collected by a telephone survey of the owner or manager of each outlet. In
      addition, alcohol purchase attempts were conducted at each outlet by youthful
      appearing study confederates. Generally, policies and practices that may reduce
      the likelihood of sales to youth were reported by a minority of outlets. Purchase
      success was found to be associated with a number of outlet characteristics,
      policies and practices. The implications of these findings for policy and future
      research are discussed.

PMID- 8857386
TI  - Contemplating the Stages of Change.

PMID- 8857387
TI  - Standing up for ourselves.

PMID- 8857388
TI  - Cultural bias and weaning.

PMID- 8857389
TI  - Should nursing mothers take ibuprofen?

PMID- 8857391
TI  - Maxed out? Mellow out with these personal stress management strategies.

PMID- 8857390
TI  - Should nursing mothers take ibuprofen?

PMID- 8857392
TI  - Drug use during pregnancy.

PMID- 8857393
TI  - Meeting the challenge of early postpartum discharge.

PMID- 8857394
TI  - Principles of informed consent.

PMID- 8857395
TI  - Inreach: linking walk-ins and their infants to community-based care.

PMID- 8857396
TI  - Nursing implications of self-care in pregnancy.

PMID- 8857397
TI  - Oral rehydration therapy. A neglected treatment for pediatric diarrhea.

PMID- 8857398
TI  - Promoting automobile safety for young children.

PMID- 8857399
TI  - Lowering the rate of unscheduled extubations.

PMID- 8857401
TI  - Laminated cards for helping battered women.

PMID- 8857400
TI  - Postpartum nursing for Korean mothers.

PMID- 8857402
TI  - Azithromycin: only once a day.

PMID- 8857403
TI  - Cancer pain.

PMID- 8857404
TI  - Pharmacologic management of cancer pain.

PMID- 8857405
TI  - Interventional management of cancer pain.

PMID- 8857406
TI  - The role of radiation therapy in the management of bone metastases.
AB  - Bone metastases are a common problem in patients with cancer and frequently
      result in significant pain and functional disability. An understanding of the
      pathogenesis of metastatic bone involvement and appropriate diagnostic evaluation
      often leads to earlier institution of palliative therapy. A substantial
      percentage of patients with bone metastases may benefit from palliative
      radiotherapy. Often, this treatment leads to rapid symptomatic improvement with
      minimal side effects.

PMID- 8857407
TI  - Rhode Island Cancer Pain Initiative and its role in physician education.

PMID- 8857408
TI  - Regulatory issues relating to the management of patients with cancer pain and
      pain of non-malignant origin.

PMID- 8857409
TI  - The costs of unrelieved pain.

PMID- 8857410
TI  - Of rodents, humankind, and cholesterol.

PMID- 8857411
TI  - Hospital stays for newborns in Rhode Island, 1993-1995.

PMID- 8857412
TI  - Rhode Island Monthly Vital Statistics Report. Provisional occurrence data from
      the Division of Vital Records.

PMID- 8857413
TI  - Andreas Vesalius, anatomist of Padua.

PMID- 8857414
TI  - Informed consent: a primer for health care practitioners.

PMID- 8857415
TI  - Coping with current issues in clinical practice:introduction.

PMID- 8857416
TI  - Clinical assessment of sexual trauma: interviewing adult survivors of childhood
      abuse.
AB  - Clinicians often feel reticent about exploring sexual trauma and its aftermath
      too soon. The author contends that, properly implemented, early exploration can
      actually foster the treatment of patients who have experienced sexual trauma.
      Appropriate clinical assessment can promote a therapeutic relationship and help
      both clinician and patient develop a comprehensive view of how the past trauma
      continues to influence the patient's current life. The author presents a detailed
      assessment outline and suggests that the findings from such an assessment can
      serve as an effective guide for further therapeutic work.

PMID- 8857417
TI  - Integrating pharmacotherapy and psychotherapy: an emerging field of study.
AB  - The mind-brain barrier is being challenged by clinicians using both medications
      and psychotherapy for the major psychiatric disorders. In this article, six
      categories of study are outlined: (1) diagnosis-specific questions, (2)
      psychotherapeutic aspects of randomized controlled medication trials, (3)
      psychotherapeutic aspects of pharmacotherapy, (4) the pharmacotherapist and the
      nonmedical psychotherapist triangle, (5) the meaning of medications during the
      stages of psychotherapy, and (6) a neurology of psychotherapy. Three categories
      are elaborated upon: (1) diagnosis-specific questions as they relate to disorder,
      (2) the meaning of medications during the stages of psychotherapy, and (3)
      neurology of psychotherapy.

PMID- 8857418
TI  - The diagnosis and treatment of mania in the elderly.
AB  - Mania in late life is often complicated by comorbid medical conditions,
      medication intolerance, and inadequate medication response. Lithium remains the
      primary medication in the acute and prophylactic treatment of mania in the
      elderly. However, certain anticonvulsants (valproic acid and carbamazepine) have
      a number of advantages, including a more tolerable side effect profile and
      increased efficacy in subgroups of patients, such as patients with secondary
      mania due to neurological and other medical disorders. Future research is needed
      to focus on the double-blind trials of somatic treatments, including ECT, in the
      elderly.

PMID- 8857419
TI  - Practitioner, heal thyself: coping with stress in clinical practice.
AB  - These are stressful times for clinical practitioners, who can benefit from
      increasing their understanding of stress response syndromes and from an enhanced
      appreciation of the constellation of stressors confronted in daily practice. The
      author reviews these stressors, as well as the signs and symptoms of the stress
      response syndrome, and suggests strategies for coping with personal and
      professional challenges.

PMID- 8857420
TI  - The manifestation and management of staff countertransference on a pediatric AIDS
      team.
AB  - The authors discuss the countertransference reactions that arise in staff who
      work in a hospital outpatient clinic with children with HIV and AIDS.
      Countertransference feelings such as guilt, anger, and helplessness can be easily
      aroused when working with a young, impoverished, dying population. Factors that
      precipitate these feelings and their manifestations are discussed, as well as the
      antitherapeutic effects of acting on one's countertransference. Psychodynamic
      explanations are offered for some of the more salient countertransference
      reactions. Finally, suggestions are made for management of countertransference,
      such as strong team leadership, ongoing support groups, and redefinition of
      therapeutic objectives.

PMID- 8857421
TI  - Understanding countertransference reactions in working with adolescent
      perpetrators of sexual abuse.
AB  - Recognizing countertransference reactions in working with adolescent perpetrators
      of sexual abuse is essential in order to provide optimal treatment. The author
      examines the broad societal reaction to these patients' acts as well as
      individual therapists' personal reactions to the material and transferences
      presented by the teenagers. Therapists' awareness of their reactions can help
      them understand the internal world of the patient and avoid destructive acting
      out of countertransference reactions.

PMID- 8857422
TI  - Munchausen-by-proxy syndrome: countertransference as a diagnostic tool.
AB  - The authors report on an unusual reaction in clinicians interviewing known
      perpetrators of Munchausen-by-proxy syndrome (MBPS): an uncanny, ego-dystonic,
      and cognitively dissonant sense that the parent could not be the perpetrator,
      despite all clinical/forensic evidence. The authors suggest that this reaction
      can have various sources: One may be "as-if" character pathology in the parent,
      with the capacity to evoke, unconsciously, disbelief in the clinician. Given the
      poor treatment outcome reported in MBPS perpetrators, the authors suggest that,
      if confirmed, this finding will lead to more accurate psychiatric diagnosis of
      the parent, and more informed treatment of this potentially harmful or lethal
      syndrome.

PMID- 8857423
TI  - Introduction. Panic disorder: critical issues in treatment.

PMID- 8857424
TI  - Quality of life and cost factors in panic disorder.
AB  - Quality of life encompasses domains of personal happiness, role fulfillment, and
      health status. Increasing attention has been paid to the relationship between
      quality of life and panic disorder, with accumulating evidence now available to
      suggest impairment in several domains among subjects with panic disorder. This
      review summarizes the results of community-based and treatment-seeking
      populations of subjects with panic disorder. Impaired personal happiness,
      restricted role functioning, and increased use of health services are all
      described. Evidence suggests that accurate diagnosis and effective treatment can
      significantly lessen health service utilization, resulting in substantial cost
      offset and also leading to increased work productivity and personal
      effectiveness.

PMID- 8857425
TI  - Panic disorder and medical comorbidity: a review of the medical and psychiatric
      literature.
AB  - Epidemiological studies have found significant comorbidity between panic disorder
      and many medical illnesses. The authors discuss the accumulating psychiatric and
      medical literature addressing comorbidity between panic disorder and cardiac,
      respiratory, gastrointestinal, and neurological illnesses. Cardiac symptoms such
      as chest pain and palpitations, as well as certain disorders such as mitral valve
      prolapse, hypertension, and cardiomyopathy, share significant comorbidity with
      panic disorder. Researchers have also shown significant comorbidity between panic
      disorder and chronic obstructive pulmonary disease, irritable bowel syndrome, and
      migraine headache. Pathophysiological mechanisms that may explain the association
      between panic disorder and comorbid medical illnesses, such as autonomic
      dysregulation of cardiac activity and smooth muscle tone and dynamic
      abnormalities of the coronary microvasculature, are discussed as well.

PMID- 8857426
TI  - Comorbidity and its effects on panic disorder.
AB  - Comorbid conditions require attention in the planning of treatment strategies for
      panic disorder, as they affect the course and prognosis of the disorder as well
      as its response to treatment. The literature documents high rates of comorbidity
      for depression, bipolar disorders, generalized anxiety disorder, social phobia,
      other anxiety disorders, and personality disorders (especially dependent and
      avoidant personality disorders). The alcohol abuse research shows comorbidity
      rates that are lower than expected from clinical reports. Although agoraphobia is
      no longer considered a comorbid disorder, its presence with panic disorder
      represents more severe disturbance and involves a higher likelihood of one or
      more comorbid diagnoses. The disorders of depression and panic are usually more
      severe when they co-occur than when only one is present. Research on the role of
      specific comorbid conditions in the outcome of treatment for panic disorder is
      reviewed.

PMID- 8857427
TI  - The pharmacotherapy of panic disorder.
AB  - The biological model for panic disorder posits a specific, genetically inherent
      neurochemical dysfunction; pharmacological treatment attempts to reregulate the
      dysregulated physiological system, thereby achieving remission (or, ideally,
      recovery) or amelioration of the symptoms sufficient for nonpharmacological
      therapies to be viable. This article will review the evidence of the efficacy of
      single classes of pharmacological agents (antidepressants, including TCAs, MAOIs,
      and SSRIs; benzodiazepines; and other agents) and integrated treatments,
      involving coadministration of medications within or across classes or a
      combination of pharmacological and nonpharmacological therapies, such as
      cognitive-behavioral therapy. Research pertaining to the relative efficacy of
      administering combination treatments concurrently or sequentially is examined.
      Individualized treatment plans for patients maximize the benefits of integrated
      treatments.

PMID- 8857428
TI  - Placebo response in the treatment of panic disorder.
AB  - A review of key placebo-controlled studies of benzodiazepines and selective
      serotonin reuptake inhibitors (SSRIs) over the past decade challenges the
      widespread view that placebo response rates resulting from clinical trials of
      pharmacotherapy for panic disorder are excessively high. Statistically and
      clinically significant drug-placebo differences have been demonstrated in large
      scale trials. Further research is needed on the impact of pharmacological
      treatments on the medium- and long-term course of the disorder.

PMID- 8857429
TI  - An integrated treatment approach to panic disorder.
AB  - After a brief description of cognitive-behavioral approaches for the treatment of
      panic disorder, the advantages and disadvantages of an integrated approach that
      combines cognitive-behavioral methods and medications are presented. This is
      followed by presentation of outcome data regarding combined treatment, and of
      methods for enhancing the implementation of an integrated approach. Finally,
      directions for future research are listed. Other psychological treatments are not
      covered due to lack of evidence for their efficacy.

PMID- 8857430
TI  - Splanchnic hypoxia after cardiac surgery.

PMID- 8857431
TI  - End-points of resuscitation: arterial blood pressure, oxygen delivery, blood
      lactate, or...?

PMID- 8857432
TI  - Lactic acidosis in sepsis: a commentary.

PMID- 8857433
TI  - Blood pressure and arterial lactate level are early indicators of short-term
      survival in human septic shock.
AB  - OBJECTIVE: To identify early prognostic markers of septic shock among
      catheterization-derived hemodynamic and metabolic data. DESIGN: Prospective
      cohort study. SETTING: A medical intensive care unit in a university hospital.
      PATIENTS: Thirty-two consecutive patients with septic shock, separated into two
      groups according to short-term (10-day) evolution: 18 acute survivors and 14
      fatalities. MEASUREMENTS: Usual hemodynamic and metabolic variables were measured
      at the onset of shock, i.e., when the catheter was inserted (T0), and 24 h later
      (T24). The values collected for each group at T0 and T24 and their 24-h changes
      were compared. RESULTS: On admission, no difference was found between acute
      survivors and eventual fatalities. After 24 h, fatalities presented with
      significantly lower mean arterial pressure (p <0.01), left ventricular stroke
      work index (p <0.05) and higher lactate levels (p <0.01) than acute survivors.
      Moreover, the 24-h changes of lactate and blood pressure were also of prognostic
      value (p <0.05). Oxygen delivery and oxygen consumption did not differ
      statistically between the two groups. At T24, a mean arterial pressure of less
      than 85 mmHg and a lactate level equal to or greater than 3.5 mmol/l were
      independently associated with poor survival (37.5% and 30.7%, respectively). Day
      10 survival was only 12.5% when both criteria were present at T24. CONCLUSIONS:
      Changes in mean arterial pressure and arterial blood lactate within the first 24
      h of treatment are strong prognostic indicators of short-term survival in
      patients with septic shock. After 24 h of treatment, maintenance of a mean blood
      pressure equal to or greater than 85 mmHg correlates with survival at day 10.
      Data suggest that early reductions in both cardiac function and vascular tone
      play a determining role in the hypotension observed in fatalities. Persistence of
      hyperlactatemia in hypotensive patients bodes particularly ill. Blood pressure
      and lactate level are simple bedside parameters that can enable the clinician to
      identify patients with a high risk of mortality.

PMID- 8857434
TI  - Splanchnic oxygen transport after cardiac surgery: evidence for inadequate tissue
      perfusion after stabilization of hemodynamics.
AB  - OBJECTIVE: To evaluate the adequacy of visceral oxygen transport and gastric pHi
      after open heart surgery in patients with stable hemodynamics. DESIGN:
      Nonrandomized control trial. SETTING: A general intensive care unit in a tertiary
      care center. PATIENTS: Sixteen postoperative cardiac surgery patients were
      studied after stabilization of systemic hemodynamics. INTERVENTIONS: The effect
      of dobutamine infusion (6 mu g kg-1 min-1) on systemic and regional oxygen
      transport was studied in ten patients, with six patients serving as controls.
      Systemic oxygen consumption was measured by indirect calorimetry and splanchnic
      and femoral blood flow, by continuous infusion of indocyanine green using
      regional catheters and gastric mucosal pHi by gastric tonometer. MEASUREMENTS AND
      RESULTS: Gastric mucosal acidosis was observed in half of the patients.
      Dobutamine increased cardiac output (3.2 +/- 0.6 vs 4.4 +/- 0.7 l x min-1 x min
      2; P <0.05), splanchnic blood flow (0.68 +/- 0.28 vs 0.91 +/- 0.28 l x min-1 x m
      2; p <0.05) and femoral blood flow (0.25 +/- 0.08 vs 0.32 +/- 0.11 l x min-1 x m
      2; p <0.05). Changes in splanchnic oxygen delivery and consumption were parallel
      in the two study groups. In response to dobutamine, gastric pHi did not change
      (7.30 +/- 0.08 vs 7.31 +/- 0.06; NS), while in the control group, gastric pHi
      tended to decrease (7.32 +/- 0.04 vs 7.28 +/- 0.06; NS). Systemic oxygen
      consumption increased in response to dobutamine (141 +/- 11 vs 149 +/- 11 ml x
      min-1 x m-2; P <0.05) but did not change in the control group. CONCLUSIONS: We
      conclude that a mismatch between splanchnic oxygen delivery and demand may be
      present despite stabilization of systemic hemodynamics after cardiac surgery.
      This is suggested by the parallel changes in splanchnic oxygen delivery and
      consumption. Dobutamine is likely to improve splanchnic tissue perfusion at this
      phase.

PMID- 8857435
TI  - Transgastric, pulsed Doppler echocardiographic determination of cardiac output.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of cardiac output
      measurement with transesophageal echocardiography (TEE) using a transgastric,
      pulsed Doppler method in acutely ill patients. DESIGN: Cardiac output was
      simultaneously measured by thermodilution (TD) and a transgastric, pulsed Doppler
      method. SETTING: The study was carried out in a surgical intensive care unit as
      part of the management protocol of the patients. PATIENTS: Thirty consecutive
      acutely ill patients with a Swan-Ganz catheter, mechanically ventilated, sedated
      and with a stable hemodynamic condition were included. MEASUREMENTS: Pulsed
      Doppler TEE was performed using a transgastric approach in order to obtain a long
      axis view of the left ventricle. Cardiac output was calculated from the left
      ventricular outflow tract diameter, the velocity time integral of the blood flow
      profile and heart rate. RESULTS: One patient was excluded because of the presence
      of aortic regurgitation and another, because of the impossibility of obtaining a
      transgastric view. Twenty-eight simultaneous measurements were performed in 28
      patients. A clinically acceptable correlation and agreement were found between
      the two methods (Doppler cardiac output = 0.889 thermodilution cardiac output
      +0.74 l/min, r = 0.975, p <0.0001). CONCLUSION: Transgastric pulsed Doppler
      measurement across the left ventricular outflow tract with TEE is a very feasible
      and clinically acceptable method for cardiac output measurement in acutely ill
      patients.

PMID- 8857436
TI  - Event-related potentials--neurophysiological tools for predicting emergence and
      early outcome from traumatic coma.
AB  - OBJECTIVE: To determine the prognostic value of multimodal evoked potentials
      (EPs) and event-related (ERPs) potentials in coma (Glasgow Coma Score <8), after
      severe traumatic brain injury (TBI). DESIGN: Prospective, longitudinal study of
      neurophysiological responses recorded during traumatic coma. SETTING: Intensive
      Care Unit, Frenchay Hospital, Bristol, UK. PARTICIPANTS: Fifty-four comatose TBI
      patients (age range 1-80 years, mean 36.4). METHODS: Neurophysiological responses
      were recorded from 11 scalp electrodes with earlobe reference. Conduction times
      were measured for brainstem auditory, flash visual and somatosensory, short
      latency EPs. Peak latencies and amplitudes were determined for long-latency
      components of visual and auditory ERPs, generated by passive "oddball" paradigms.
      These neurophysiological and various clinical parameters were correlated with
      patient outcome using Pearson's coefficient. MAIN OUTCOME MEASURE: Three month
      Glasgow Outcome Scale (GOS). RESULTS AND CONCLUSION: Highly significant (P
      <0.001) correlations exist between long-latency ERP components and 3-month
      outcome. Short-latency EPs, brainstem (wave I-V) and somatosensory conduction
      times also correlate significantly with the GOS (P <0.01). Of the clinical
      measurements, pupillary response patterns, APACHE II and Glasgow Coma Scores
      (GCS) correlate significantly with outcome, as do the retrospective measures of
      duration of coma and post-traumatic amnesia (PTA) in survivors. Unfortunately,
      due to variance of long-latency responses, even in controls, absolute values
      cannot be relied upon as prognosticators. The presence of "mismatch negativity"
      predicted the return of consciousness (89.7% sensitivity and 100% specificity)
      and preceded changes in GCS. Its latency was the single best indicator of 90-day
      outcome from coma (r = -0.641).

PMID- 8857437
TI  - Influence of severe hemodilution on brain function and brain oxidative metabolism
      in the cat.
AB  - OBJECTIVE: It has been established that during constant pressure arterio-venous
      bypass perfusion, brain metabolism gradually deteriorates in parallel with the
      declining hematocrit. However, whether this is due to a disturbance of flow
      regulation or to the decline in the oxygen-carrying capacity of the blood has not
      been documented. Therefore, intact animals were submitted to severe hemodilution
      to determine the threshold for the beginning of functional and biochemical
      impairment of the brain. METHODS: Six anesthetized and paralyzed adult mongrel
      cats were submitted to gradual isovolemic hemodilution by stepwise exchange of
      blood with Ringer lactate/dextran (1 : 1) solution. Exchange of 80 ml/kg body
      weight resulted in a final hematocrit level ranging from 6.1% to 11%. RESULTS:
      Cerebral blood flow gradually increased during hemodilution, with a sharp rise to
      eight times the prehemodilution value when the hematocrit fell below 10%. The
      calculated oxygen delivery to the brain remained relatively unchanged.
      Hemodilution did not cause suppression of spontaneous ECoG or somatically evoked
      primary cortical potentials, even at the lowest hematocrit value of 6.1%. Brain
      tissue ATP and phosphocreatine content were largely maintained, although tissue
      lactate content was elevated (9.54 +/- 5.99 micromol/g). CONCLUSIONS: The
      hemodynamically unimpaired healthy mammal is able to support a substantial degree
      of hemodilution without major functional or biochemical disturbance to the brain.
      The previously observed disturbances during prolonged bypass perfusion are,
      therefore, most probably due to the associated abnormalities of flow regulation.

PMID- 8857438
TI  - Endothelin production in sepsis and the adult respiratory distress syndrome.
AB  - OBJECTIVE: Septic shock is characterised by a decrease in systemic vascular
      resistance. Nevertheless, regional increases in vascular resistance can occur
      which may predispose to organ dysfunction, including the adult respiratory
      distress syndrome (ARDS). Because endothelial damage is a major feature of acute
      lung injury, we examined whether the potent endothelial vasoconstrictor peptide
      endothelin-1 plays a pathophysiological role in sepsis or ARDS. DESIGN: Plasma
      endothelin was measured in mixed venous, pulmonary capillary and arterial blood,
      and the relationship with outcome measures was determined. SETTING: The intensive
      care unit of a university teaching hospital. PATIENTS AND PARTICIPANTS: A
      consecutive series of well-characterised patients with sepsis syndrome, both with
      (n = 11) and without (n = 15) ARDS, and ventilated controls without sepsis or
      ARDS (n = 7). MEASUREMENTS AND RESULTS: Plasma endothelin was significantly
      elevated in patients with sepsis alone and in patients with sepsis and ARDS.
      Plasma endothelin did not differ among mixed venous, pulmonary capillary and
      systemic arterial blood. On multiple regression analysis, plasma endothelin
      correlated positively with organ failure score and with oxygen consumption, and
      negatively with the PaO2 : FiO2 ratio. There was no correlation with plasma
      creatinine, suggesting that decreased renal clearance did not account for the
      high plasma endothelin concentrations. CONCLUSIONS: Although the lung does not
      appear to be the major site of endothelin production in critically ill patients
      with sepsis, increased endothelin production may contribute to regional increases
      in vascular [correction of vacular] resistance, hyperfusion, and the development
      of organ failure, including ARDS, in patients with sepsis.

PMID- 8857439
TI  - Buflomedil poisoning: five cases with cardiotoxicity.
AB  - OBJECTIVE: To report cardiotoxicity of buflomedil. SETTING: Medical intensive
      care unit of a university hospital. PATIENTS: Five patients admitted to the
      hospital since 1985 for buflomedil poisoning. The amount ingested was known for
      only three patients (3-10.8 g). RESULTS: The five young women were admitted to
      the hospital because of generalized seizures or myoclonic jerks. Cardiac arrest
      (asystole) occurred for two of them on admission, 1 and 3 h after ingestion.
      Electrocardiogram revealed atrio-ventricular and intraventricular conduction
      abnormalities, increased QT interval and flattened T wave, decreasing after
      sodium bicarbonate infusion in two cases. The patients received mechanical
      ventilation, gastric lavage, oral activated charcoal, and clonazepam or valproic
      acid for convulsions or myoclonic jerks. Epinephrine was administered for cardiac
      arrest. Sodium bicarbonate was infused in one patient on the basis of slightly
      prolonged QRS duration and in two patients due to cardiac arrest. Clinical
      outcome was good and without sequelae for all five patients after a few days in
      the intensive care unit. CONCLUSION: Clinical and electrocardiographic
      symptomatology of buflomedil poisoning suggests direct cardiotoxicity, which
      could be related to possible sodium antagonist properties.

PMID- 8857440
TI  - Arrhythmias and ischemia-like ECG changes in Reye's syndrome.
AB  - We report a fatal case of a child presenting Reye's syndrome associated with a
      variety of arrhythmias and ischemia-like ST-T ECG changes. At autopsy, fatty
      infiltration and patchy myocytolysis were detected in sections of the heart. This
      case report emphasizes cardiac involvement in Reye's syndrome and the possible
      mechanisms of arrhythmias in this disease.

PMID- 8857441
TI  - Circulatory and diuretic effects of dopexamine infusion in low-birth-weight
      infants with respiratory failure.
AB  - OBJECTIVE: To investigate the effects of infusion of dopexamine hydrochloride, a
      new synthetic catecholamine, on cardiopulmonary status and urine output in
      neonates with respiratory and circulatory failure. DESIGN: Prospective clinical
      study with each patient serving as his own control. SETTING: Intensive care unit
      (14 beds) in a 300-bed paediatric teaching hospital. PATIENTS: Seventeen neonates
      with low birth weight (LBW) requiring mechanical ventilation in the first 4 days
      of life, who initially had two of the following symptoms: hypotension, oliguria,
      metabolic acidosis with base deficit >10 and failure to respond to volume
      loading. INTERVENTIONS: Cardiopulmonary variables, diuresis and acid-base status
      were measured before and after volume loading, in patients who did not improve
      infusion of dopexamine was started at a dose of 2 microg kg-1 min-1 which was
      titrated to achieve blood pressure, urine output, and base deficit in normal
      range. Observations were continued for a period of 5 h. MEASUREMENTS AND RESULTS:
      Systolic blood pressure increased significantly after 3 h. of dopexamine infusion
      and remained elevated up to the end of the study period. Diastolic and mean blood
      pressure increased slightly (NS). Diuresis increased significantly from the 4th h
      of dopexamine infusion. Arterial blood pH increased significantly from baseline
      at 5 h after the start of dopexamine administration. There was also a significant
      improvement in the PtcO2/PaO2 index. CONCLUSION: In neonates with respiratory and
      circulatory failure, dopexamine increases blood pressure and improves arterial pH
      and urine output.

PMID- 8857442
TI  - Inhaled nitric oxide for avoidance of extracorporeal membrane oxygenation in the
      treatment of severe persistent pulmonary hypertension of the newborn.
AB  - Inhaled nitric oxide (NO) is thought to provide a noninvasive therapeutic
      alternative to extracorporeal membrane oxygenation (ECMO) in the treatment of
      persistent pulmonary hypertension of the newborn (PPHN). OBJECTIVE: Since January
      1993, we have studied inhalation of NO in PPHN patients meeting the ECMO criteria
      of our institution. We focused on the questions of whether or not the need for
      ECMO could be obviated and whether differences could be found between NO
      responders and nonresponders. DESIGN: NO gas was delivered via conventional IPPV
      ventilation in incrementally increasing concentrations from 20 to 80 ppm.
      PATIENTS: NO therapy was attempted in ten ECMO candidates with clinical and
      echocardiographical evidence of PPHN (mean OI 51.9, SD 10.4). RESULTS: At various
      NO levels (30-60 ppm), five patients showed a significant increase in mean PaO2
      (range 32.9-85.9 mmHg). Improvement was transient in three patients (6-10 h) and
      prolonged in two others (54-80 h); in the latter cases, ECMO was avoided. Five
      patients did not respond at all to treatment. Responders and nonresponders
      differed in their mean respiratory tidal volume (8.9 vs 4.18 ml/kg, P <0.05).
      CONCLUSIONS: In our study, inhalation of NO obviated the necessity of ECMO
      therapy in only two out of ten PPHN patients. Thus, we would discourage any
      overoptimistic expectations about the effectiveness of NO therapy in PPHN until
      larger clinical trials have been performed.

PMID- 8857443
TI  - Delivery and monitoring of inhaled nitric oxide.
AB  - Inhaled nitric oxide is rapidly gaining popularity as a selective pulmonary
      vasodilator in patients with acute lung injury and pulmonary hypertension. The
      development of nitric oxide as a drug has bypassed the usual regulatory and
      commercial processes, and as a result clinicians have devised a wide range of
      delivery and monitoring systems. This review describes these systems, and
      discusses their advantages, disadvantages and safety. The monitoring of nitric
      oxide metabolites is also discussed.

PMID- 8857444
TI  - Exogenous surfactant therapy for acute respiratory distress in infancy.

PMID- 8857445
TI  - Use of the flow-volume loop to detect secretions in ventilated children.

PMID- 8857446
TI  - Overview of biliary diseases.

PMID- 8857447
TI  - Can we do away with PTBD?
AB  - Percutaneous Transhepatic Biliary Drainage (PTBD) is performed in surgical
      jaundice to decompress the biliary tree and improve hepatic functions. However,
      the risk of sepsis is high in these patients due to immunosuppression and
      surgical outcome remains poor. This raises a question--can we do away with PTBD?
      To answer this query a study was carried out in 4 groups of patients bearing in
      mind the high incidence of sepsis and our earlier studies, which have
      demonstrated immunotherapeutic potential of Tinospora cordifolia (TC): (A) those
      undergoing surgery without PTBD (n = 14), (B) those undergoing surgery after PTBD
      (n = 13). The mortality was 57.14% in Group A as compared to 61.54% in Group B.
      Serial estimations of bilirubin levels carried out during the course of drainage
      (3 Wks) revealed a gradual and significant decrease from 12.52 +/- 8.3 mg% to
      5.85 +/- 3.0 mg%. Antipyrine half-life did not change significantly (18.35 +/-
      4.2 hrs compared to basal values 21.96 +/- 3.78 hrs). The phagocytic and
      intracellular killing (ICK) capacities of PMN remained suppressed (Basal: 22.13
      +/- 3.68% phago. and 19.1 +/- 4.49% ICK; Post drainage: 20 +/- 8.48% Phago and
      11.15 +/- 3.05% ICK). Thus PTBD did not improve the metabolic capacity of the
      liver and mortality was higher due to sepsis. Group (C) patients received TC
      during PTBD (n = 16) and Group (D) patients received TC without PTBD (n = 14). A
      significant improvement in PMN functions occurred by 3 weeks in both groups
      (30.29 +/- 4.68% phago, 30 +/- 4.84% ICK in Group C and 30.4 +/- 2.99% phago,
      27.15 +/- 6.19% ICK in Group D). The mortality in Groups C and D was 25% and
      14.2% respectively during the preoperative period. There was no mortality after
      surgery. It appears from this study that host defenses as reflected by PMN
      functions play an important role in influencing prognosis. Further decompression
      of the biliary tree by PTBD seems unwarranted.

PMID- 8857448
TI  - Evaluation of liver function tests to predict operative risk in liver surgery.
AB  - Despite numerous studies in the past it is not possible yet to predict
      postoperative liver failure and safe limits for hepatectomy. In this study the
      following liver function tests ICG-ER (indocyaninegreen elimination rate), GEC
      (galactose elimination capacity) and MEGX-F (monoethylglycinexylidid formation)
      are examined with regard to loss of liver tissue and prediction of operative
      risk. Liver function tests were assessed in 20 patients prior to liver resection
      and on the 10th. postoperative day. Liver and tumor volume were measured by
      ultrasound and pathologic specimen and the parenchymal resection rate was
      calculated. In patients without cirrhosis (n = 10) ICG-ER and MEGX-F remained
      unchanged after resection, GEC was reduced but did not correspond to the
      resection rate. Patients with cirrhosis (n = 10) had a significantly lower ICG-ER
      and GEC before resection than patients without cirrhosis. After resection these
      tests were unchanged. Patients with liver related complications and cirrhosis (n
      = 5) had lower ICG-ER and GEC than patients with cirrhosis and no complications.
      In the postoperative course all liver function tests in these patients were
      significantly lower compared to preoperative results. Comparing liver function
      tests ICG serves best to indicate postoperative liver failure. Liver function
      tests do not correspond with loss of liver tissue.

PMID- 8857449
TI  - Surgical workshop on liver surgery using isolated perfused livers in moulded
      casts of the upper abdomen.
AB  - The basic training in liver surgery on isolated perfused livers used at the
      workshop in the First Surgical Course of the Alps--Adriatic Hepatobiliary School
      is presented. The methods for the excision, preservation, perfusion and
      preparation of the liver are described, as is the manner of manufacturing the
      upper abdomen moulded casts, into which an isolated perfused liver is placed for
      training. The methods proved to be sufficiently successful, enabling participants
      to perform basic liver surgery like an intraoperative ultrasound investigation,
      as well as liver dissection techniques, liver suturing, segmental resection and
      even hepatectomy. Some technical improvements are proposed for future surgical
      workshops, such as washing out the blood from the liver, and a triple perfusion.

PMID- 8857450
TI  - Emblica officinalis: a novel therapy for acute pancreatitis--an experimental
      study.
AB  - Acute necrotising pancreatitis is associated with an unacceptably high mortality
      for which no satisfactory remedy exists. Emblica officinalis (E.o.) is a plant
      prescribed in Ayurveda, the Indian traditional system of medicine, for pancreas
      related disorders. This study was carried out to evaluate the protective effect
      of E.o. against acute necrotising pancreatitis in dogs. Pancreatitis was induced
      by injecting a mixture of trypsin, bile and blood into the duodenal opening of
      the pancreatic duct. Twenty eight dogs were divided into 4 groups (n = 6-8 each):
      GpI--control, GpII--acute pancreatitis, GpIII--sham-operated, GpIV--pretreatment
      with 28 mg E.o./kg/day for 15 days before inducing pancreatitis. Serum amylase
      increased from 541.99 +/- 129.13 IU/ml to 1592.63 +/- 327.83 IU (p <0.02) 2 hrs
      after the induction of pancreatitis in GpII. The rise in serum amylase in both
      GpIII and GpIV was not significant. On light microscopic examination, acinar cell
      damage was less and the total inflammatory score was significantly lower in the
      E.o. treated group as compared to GpII. Electron microscopy confirmed this and
      showed an increased amount of smooth endoplasmic reticulum and small, condensed
      granules embedded in a vacuole. More studies are needed to explore the clinical
      potential of E.o. and its mechanism of action.

PMID- 8857451
TI  - Duodenal varices: a case report and review of the literature.

PMID- 8857452
TI  - Long-term results of hepatic resection for hepatolithiasis.
AB  - Long-term results of hepatic resection for hepatolithiasis in 34 patients having
      intrahepatic biliary strictures were studied. The left lateral and the right
      posterior segmental ducts were commonly and often simultaneously involved.
      Fourteen patients had multiple segmental involvement. Hepatic resection included
      left sided resection (n = 27), right sided resection (n = 6), and repeated
      bilateral resection (n = 1). Seven patients had biliary tumors: 3
      cholangiocarcinomas, 2 gall bladder cancers, 1 cystadenocarcinoma, and 1
      dysplasia of intrahepatic ducts. Nineteen patients received bilioenteric
      anastomosis. Retained stones and recurrent stones developed in 3 and 4 patients,
      respectively. Twenty-six patients had no remaining symptoms; 2 died of operative
      complication or cholangiocarcinoma; 6 presented symptoms caused by retained
      stones (n = 2), recurrent stones (n = 2), bile stasis (n = 1), or neuralgia (n =
      1). In 4 of the 6 patients, unrelieved posterior duct strictures caused the
      symptoms. With a mean follow-up period of 4.5 years, 30 patients are symptoms
      free, and 27 are stone free. In patients with right lobar or bilobar type, intra-
      and extrahepatic type, and confluence strictures, bilioenteric anastomosis is
      required. Hepatic resection is a rational treatment for hepatolithiasis, however,
      meticulous management of biliary tract abnormalities, particularly the posterior
      duct stricture, is mandatory.

PMID- 8857453
TI  - Definitive surgical treatment for cholelithiasis in selected patients with liver
      cirrhosis.
AB  - To determine whether definitive surgery such as cholecysectomy or extraction of
      bile duct stones is appropriate in cirrhotic patients the results of definitive
      surgery have been reviewed retrospectively in a group of 112 cirrhotic patients
      with cholelithiasis. Eighty-seven of these patients underwent definitive surgery
      for gallstones and the remaining 25 were treated conservatively. Child's criteria
      were applied to each patient. Patients with Child's grade A disease had fewer
      emergency procedures, operative blood loss and transfusion were less and they had
      a shorter hospital stay compared with patients with grades B and C. There were 4
      deaths after definitive surgery for emergency conditions and these were all in
      Child's grade C. Of the 83 survivors after definitive procedures 78 patients
      (93.9%) were still alive 52.8 months later without any biliary tract symptoms. Of
      the 25 patients undergoing conservative treatment 2 were Child's B and 23 were
      Child's C grade. We suggest that definitive surgery can be carried out safely, in
      Child's A and B cirrhotic patients, either electively or as an emergency.
      However, a more conservative approach is advisable in Child C patients with acute
      conditions and definitive surgery is recommended as an elective procedure after
      the liver function has improved.

PMID- 8857454
TI  - Hepatoblastoma in an adult with biliary obstruction and associated portal venous
      thrombosis.
AB  - We present a case of adult hepatoblastoma. This young female presented with
      severe acute cholangitis. Preoperative diagnosis was common bile duct (CBD)
      obstruction with portal vein thrombosis. On exploration she had a tumor mass in
      the CBD. The unusual features of this case are discussed in this report.

PMID- 8857455
TI  - Fibrolamellar hepatocellular carcinoma "it is not a ordinary case for
      Mediterranean countries".
AB  - The fibrolamellar variant of hepatocellular carcinoma (HCC) is an uncommon tumour
      with distinctive clinical and histological features. Although the first case of
      fibrolamellar hepatocellular carcinoma (FI-HCC) was described by Edmondson in
      1956, and later confirmed in five patients by Peters, the majority of reports
      followed those of Berman et al. and Craig et al. A case of FI-HCC, which is
      rarely diagnosed in Mediterranean countries including Turkey, is presented in the
      following report.

PMID- 8857456
TI  - Hypersplenism in liver cirrhosis: is conservative treatment still best?

PMID- 8857457
TI  - Activation of liver cirrhosis: control by lymphosorbtion.

PMID- 8857458
TI  - Question on gender.

PMID- 8857459
TI  - In-hospital patients with aphasia, dysarthria deserve our attention.

PMID- 8857460
TI  - State Tech Act projects reach out to families.

PMID- 8857461
TI  - AFA takes issue with ASHA.

PMID- 8857462
TI  - Your association, past, present, and ...future perfect?

PMID- 8857463
TI  - (Un)civilized speech. Should ASHA care?

PMID- 8857464
TI  - GADabouts!

PMID- 8857466
TI  - Orofacial myofunctional disorders.

PMID- 8857465
TI  - Actuary data: what's in it for you?

PMID- 8857467
TI  - Internet. More commands to remember.

PMID- 8857468
TI  - The perils of free speech. Carefully craft your compliments!

PMID- 8857469
TI  - Contamination in reasoning about false belief: an instance of realist bias in
      adults but not children.
AB  - Children aged around 5 and 9 years and adults were presented with stories and
      videos about a protagonist who heard a message purporting to provide factual
      information. Observing subjects knew whether the message was true or false. In
      some cases, this message contradicted the listener's existing belief based on
      what he or she had seen previously. Subjects judged whether the listener would
      believe or disbelieve the message. Child subjects frequently judged that a
      contradicting message would be disbelieved, irrespective of whether they (the
      child subjects) knew it to be true or false. In contrast, adult subjects made
      judgements that were contaminated by their own privileged knowledge of the truth.
      For three different scenarios, adult subjects judged more frequently that the
      message would be believed if they (but not the listener protagonist) knew it to
      be true, than if they thought it was false.

PMID- 8857470
TI  - Recency preference in the human sentence processing mechanism.
AB  - Cuetos and Mitchell (1988) observed that in constructions in which a relative
      clause can attach to one of two possible sites, English speakers prefer the more
      recent attachment site, but Spanish speakers prefer the least recent attachment
      site, in violation of the proposed universal principle Late Closure (Recency
      Preference), which favors attachments to the most recent sites. Based on this
      evidence, Cuetos and Mitchell concluded that Late Closure is not a universal
      principle of the human sentence processing mechanism. In this paper, we provide
      new evidence from Spanish and English self-paced reading experiments on relative
      clause attachment ambiguities that involve three possible attachment sites. The
      results of our experiments suggest that a principle like Late Closure is in fact
      universally operative in the human parser, but that it is modulated by at least
      one other factor in the processing of relative clause attachment ambiguities. We
      propose that the second factor involved in the processing of these and related
      constructions is the principle of Predicate Proximity, according to which
      attachments are preferred to be as structurally close to the head of a predicate
      phrase as possible, and we further consider the origins and predictions of the
      theory combining these two factors.

PMID- 8857471
TI  - Sequential and coordinative processing dynamics in figural transformations across
      the life span.
AB  - This work tests the proposition that two distinct factors involved in life span
      cognitive development are mental speed and coordination efficiency. Dynamics of
      information processing in a figural transformation task were assessed via time
      accuracy functions for children (mean age = 9.5 years), young adults (mean age =
      23.7 years), and old adults (mean age = 73.7 years). Corresponding to the two
      proposed factors, speed and coordination, both sequential and coordinative
      aspects of complexity were varied. Sequential complexity was manipulated through
      the number of objects to be checked for transformations; coordinative complexity
      was manipulated through the number of transformations to be considered
      simultaneously. Individual time--accuracy operating characteristics were
      adequately described by exponential functions for all age and complexity levels.
      Complexity-specific effects confirmed the general expectation of a particularly
      large age sensitivity of coordinative functions. Proportional adult age effects
      in the processing time parameter were larger for coordinatively complex than for
      sequentially complex conditions. For the contrast between children and young
      adults this was the case only for high coordinative complexity. Results are
      interpreted in terms of (a) dissociable developmental changes in speed of
      processing and working memory functioning across the life span and (b)
      differential effects of coordinative demands in children and old adults.

PMID- 8857472
TI  - When do speakers take into account common ground?
AB  - What role does common ground play in the production of utterances? We outline and
      test two models. One model assumes that common ground is involved in initial
      utterance planning, while the other model assumes that it only plays a role in
      monitoring. To compare these models, we focus on common ground as evidenced in
      physical co-presence. We had speakers describe objects for listeners in a
      modified version of the referential communication task. While descriptions under
      no time constraints appeared to incorporate common ground with the listener,
      common ground was not used when the speakers were under time pressure. These
      results suggest that speakers do not engage in audience design in the initial
      planning of utterances; instead, they monitor those plans for violations of
      common ground.

PMID- 8857473
TI  - Effect of late percutaneous angioplastic recanalization of total coronary artery
      occlusion on left ventricular remodeling, ejection fraction, and regional wall
      motion.
AB  - The clinical benefit of late recanalization of complete coronary occlusion is
      debated. Left ventricular (LV) function and volumes are major prognostic
      determinants in patients with coronary artery disease. We sought to assess
      comprehensively the evolution of global and regional LV function and LV volumes
      after percutaneous recanalization of chronic complete coronary artery occlusions.
      A consecutive series of 55 patients who underwent successful percutaneous
      recanalization of a chronic (> or = 10 days), total (Thrombolysis in Myocardial
      Infarction trial flow grade 0) occlusion of the left anterior descending or
      dominant right coronary arteries, and in whom a complete angiographic evaluation
      was available before angioplasty and at follow-up was studied. At follow-up, 38
      patients had a patent artery (group 1) and 17 had a reocclusion (group 2).
      Baseline parameters were similar in the 2 groups. In group 1, LV ejection
      fraction increased from 55 +/- 14% to 62 +/- 13% (p <0.001), with an increase in
      fractional shortening in the occluded artery territory (0.43 +/- 0.30 to 0.71 +/-
      0.34, p <0.001), while LV end-diastolic volume remained unchanged. In group 2,
      ejection fraction and regional wall motion were unchanged, while LV end-diastolic
      volume index increased (86 +/- 22 ml/m2 to 99 +/- 34 ml/m2, p <0.02). The
      evolution in LV global and regional function was similar in patients with or
      without previous myocardial infarction; however, prevention of LV remodeling was
      observed only in patients with previous infarction. Maintained potency after
      successful recanalization of totally occluded coronary arteries improves global
      and regional LV function and, in patients with previous myocardial infarction,
      avoids LV remodeling.

PMID- 8857474
TI  - Prediction of late cardiac events by dipyridamole thallium scintigraphy in
      patients with intermittent claudication and occult coronary artery disease.
AB  - Concomitant coronary artery disease often occurs in patients with peripheral
      vascular disease, but it may be asymptomatic. Despite being asymptomatic,
      cardiovascular events are the main source of morbidity and mortality in this
      group of patients. Dipyridamole thallium scintigraphy has been shown to be of
      prognostic value in patients with peripheral vascular disease and symptomatic
      coronary artery disease, but its effect on the long-term outcome in the
      asymptomatic group of patients is less defined. Eighty-four consecutive patients
      with peripheral vascular disease and no symptoms of coronary artery disease were
      therefore evaluated by clinical assessment, dipyridamole thallium imaging,
      radionuclide ventriculography, and cardiac catheterization and followed for a
      mean of 66 months. Abnormal perfusion patterns were found on thallium
      scintigraphy in 48 patients (57%); fixed, mixed, and reversible defects were
      present in 14 (17%), 11 (13%), and 23 (27%) patients, respectively. Significant
      coronary artery disease was present in 52 patients (69%) and mean left
      ventricular ejection fraction was 44%. During the follow-up period, 23 patients
      had a cardiac event (nonfatal myocardial infarction or cardiac death). Univariate
      analysis of 15 clinical, scintigraphic, radionuclide, and angiographic variables
      revealed that age, angiographic extent of coronary artery disease, and an
      abnormal thallium scan were significant predictors of subsequent cardiac events.
      Multivariate stepwise logistic regression analyses selected fixed and mixed
      thallium defects and diffuse coronary artery disease as the only significant
      independent predictors of outcome. Thus, the present study shows the value of
      dipyridamole thallium scintigraphy as a valuable prognostic indicator for long
      term event-free survival in a cohort of patients with peripheral vascular disease
      and no history or symptoms of coronary artery disease.

PMID- 8857475
TI  - Effect of coronary artery size on the prevalence of atherosclerosis.
AB  - To investigate the effect of coronary artery size on the prevalence of
      atherosclerosis, we measured the diameters of the major coronary arteries
      prospectively in 884 consecutive patients referred for coronary arteriography.
      For each artery, we assigned patients to 3 groups: group S (small) and group L
      (large) with diameters >1SD smaller and larger, respectively, than the mean; and
      group A (average), with diameters within 1SD of the mean. As specified during
      study design, we compared the frequency of lesions > or = 50% diameter stenosis
      in groups S and L for each artery. We adjusted for relevant covariates by
      performing logistic regression on data from all 884 patients with coronary
      diameter entered as a continuous variable. In group S versus L, respectively, the
      frequency of > or = 50% lesion was 6.5% versus 2.4% (p = 0.13) in the left main
      artery; 61.3% versus 35.8% (p = 0.0001) in the right coronary artery; 58.1%
      versus 40.7% (p = 0.008) in the left anterior descending artery, and 47.4% versus
      22.2% (p = 0.0001) in the circumflex artery. Multivariate analysis showed that
      coronary diameter was a significant independent predictor of lesions in the right
      coronary artery (p = 0.000001), left anterior descending artery (p = 0.001), and
      circumflex artery (p = 0.0002) and nearly significant in the left main artery (p
      = 0.077). Thus, small coronary artery size may be a risk factor for
      atherosclerosis.

PMID- 8857476
TI  - Poloxamer-188 as an adjunct to primary percutaneous transluminal coronary
      angioplasty for acute myocardial infarction.
AB  - Poloxamer-188 is a surfactant polymer with antithrombotic and hemorheologic
      properties that make it potentially useful as an adjunct to acute reperfusion
      strategies. Animal studies and early human studies have documented poloxamer-188
      to be effective at improving myocardial salvage when used as an adjunct to
      intravenous thrombolytic therapy for acute myocardial infarction. The current
      trial was a prospective pilot study involving 150 patients who were randomized in
      a 2:1 fashion to a poloxamer-188 infusion for 48-hours versus placebo. The
      poloxamer-188 infusion was well tolerated subjectively. The only clinically
      significant laboratory abnormality noted was an elevation in the serum creatinine
      above 2.0 g/dl in 12% (n = 12) of the 98 poloxamer-188 treated patients versus 1
      of the 52 (2%) of the placebo treated patients (p = 0.048). Clinical end points
      including reinfarction (1% vs 4%), cardiogenic shock (7% vs 6%), and death (9% vs
      4%) were statistically similar in the poloxamer-188 and placebo groups,
      respectively (p = NS). Using quantitative nuclear techniques, final infarct size
      and myocardial salvage were statistically similar in the poloxamer-188 and
      placebo groups. Mean left ventricular ejection fractions 1 week post after
      infarction were 51% +/- 12% in the poloxamer-188 group and 52% +/- 13% in the
      placebo group (p = NS). Final infarct size, was not altered by the poloxamer- 188
      infusion; however, it was significantly correlated with normal perfusion
      (Thrombolysis in Myocardial Infarction grade 3 flow) in the infarct vessel after
      angioplasty. This study documented poloxamer-188 to be ineffective as an adjunct
      to primary angioplasty for acute myocardial infarction and resulted in azotemia
      in 12% of the patients.

PMID- 8857477
TI  - Myocardial infarction as a complication of new interventional devices.
AB  - Percutaneous transluminal coronary balloon angioplasty has been associated with
      acute myocardial infarction (MI) as a complication of the procedure. Abrupt
      closure, distal coronary embolization, intimal dissection, coronary spasm, and
      acute thrombosis are the principal etiologies. New interventional devices (stent,
      laser, and atherectomy catheters) have been introduced as alternatives or
      adjuncts to balloon angioplasty. With use of the New Approaches to Coronary
      Intervention Registry, the incidence, predictors, and outcome of MI as a
      complication of using these devices as the primary mode of intervention were
      studied. There were 3,265 patients from 39 participating centers in the cohort
      treated with new devices. MI was reported as an in-hospital complication of using
      new devices in 154 patients (4.7%), including Q-wave MI in 36 patients (1.1%),
      and non-Q-wave MI in 119 patients (3.6%). MI rates were not significantly
      different among all patients with devices in the cohort treated with atherectomy
      (directional, extractional, rotational), laser (AIS, Spectranetics) or the Palmaz
      Schatz stent. Multivariate logistic regression showed that post-procedure MI was
      associated with multivessel disease, high surgical risk, postinfarction angina,
      and presence of a thrombus prior to the procedure. Prior percutaneous
      transluminal coronary angioplasty was inversely related to the incidence of MI.
      When a specific cause of MI could be detected, the main etiologies were: coronary
      embolus 16.9%, and abrupt closure 27.3%. Other major in-hospital complications
      were higher in the MI group than the non-MI group: death 7.8% versus 0.8% (p
      <0.001), and bypass surgery 13.6% versus 1.7% (p <0.001). At 1 year, mortality
      rates remain higher at 12.9% in the MI group versus 4.9% in the non-MI group (p
      <0.01). Despite different indications for the use of new devices, they were not
      predictors for MI with the exception of the rotablator. The incidence of MI (1.1%
      Q-wave, 3.6% non-Q-wave) was comparable to previously reported rates for balloon
      angioplasty. The occurrence of MI is associated with an increase in other in
      hospital complications and a doubling of 1-year mortality.

PMID- 8857478
TI  - Excimer laser angioplasty versus balloon angioplasty in functional and total
      coronary occlusions.
AB  - Registries of excimer laser coronary angioplasty have reported good results in
      the treatment of complex coronary artery disease, including total or subtotal
      coronary occlusions. One hundred three patients (103 lesions) with a functional
      or total coronary occlusion were included in a randomized trial (Amsterdam
      Rotterdam [AMRO] trial, total of 308 patients), 49 patients were allocated to
      laser angioplasty and 54 patients to balloon angioplasty. The primary clinical
      end points were death, myocardial infarction, coronary bypass surgery, or
      repeated coronary angioplasty of the randomized segment during a 6-month follow
      up period. The primary angiographic end point was the minimal lumen diameter at
      follow-up in relation to the baseline value (net gain), as determined by an
      automated contour-detection algorithm. Laser angioplasty was followed by balloon
      angioplasty in all procedures. The angiographic success rate was 65% in patients
      treated with excimer laser-assisted balloon angioplasty compared with 61% in
      patients treated with balloon angioplasty alone. No deaths occurred. There were
      no significant differences between the laser angioplasty group and the balloon
      angioplasty group in the incidence of myocardial infarctions (1 patient vs 3,
      respectively, p = 0.36), coronary bypass surgery (4 patients vs 2, respectively,
      p = 0.34), repeat angioplasty (10 patients vs 8, respectively, p = 0.46) or
      primary clinical end point (15 patients vs 12, respectively, p = 0.34). The net
      gain in minimal lumen diameter and restenosis rate (>50% diameter stenosis at
      follow-up) were 0.81 +/- 0.74 mm and 66.7%, respectively, in patients treated
      with laser angioplasty compared with 1.04 +/- 0.68 mm and 48.5%, respectively, in
      patients treated with balloon angioplasty (p = 0.59 and p = 0.15, respectively).
      Excimer laser-assisted balloon angioplasty demonstrated no benefit over balloon
      angioplasty with respect to initial and long-term clinical and angiographic
      outcome in the treatment of patients with functional or total coronary occlusions
      of >10 mm in length.

PMID- 8857479
TI  - Effects of short-term reduction in serum cholesterol with simvastatin in patients
      with stable angina pectoris and mild to moderate hypercholesterolemia.
AB  - To evaluate the effects of short-term cholesterol-lowering treatment on
      myocardial effort ischemia, 22 patients with stable effort ischemia and mild to
      moderate hypercholesterolemia (low density lipoprotein [LDL] cholesterol 160 to
      220 mg/dl) were randomly allocated at baseline (TO) in 2 groups. Group A included
      12 patients treated with simvastatin 10 mg bid; group B included 10 patients
      treated with placebo. All patients underwent a treadmill electrocardiography
      (ECG) test; total cholesterol, HDL and LDL cholesterol, triglycerides, plasma,
      and blood viscosity were measured. All tests were repeated after 4 and 12 weeks.
      For 18 of the same patients (11 taking simvastatin, 7 receiving placebo), forearm
      strain-gouge plethysmography was performed at baseline and after 4 weeks, both at
      rest and during reactive hyperemia. At 4 and 12 weeks, group A showed a
      significant reduction in total cholesterol (p <0.05) and LDL (p <0.05), with
      unchanged HDL, triglycerides, blood, and plasma viscosity. Effort was unmodified,
      ST-segment depression at peak effort and ischemic threshold were significantly
      improved after 4 and 12 weeks (all p <0.05) with unchanged heart rate x systolic
      blood pressure product. A significant increase in the excess flow response to
      reactive hyperemia was detected in group A (p <0.03); group B showed no changes
      in hematochemical and ergometric parameters. These data suggest that cholesterol
      lowering treatment is associated with an improvement in myocardial effort
      ischemia; this might be explained by a more pronounced increase of coronary blood
      flow and capacity of vasodilation in response to effort.

PMID- 8857480
TI  - Comparison of standard- and extended-length participation in cardiac
      rehabilitation on body composition, functional capacity, and blood lipids.
AB  - Participation in a standard-length outpatient cardiac rehabilitation program
      (CRP) for 3 months is known to result in positive changes in body composition,
      functional capacity, and blood lipids in patients with coronary artery disease.
      However, there has been little attempt to compare patients who remain active in a
      formal CRP for an extended length of >1 year with patients who exit after a
      standard length of 3 months. Consequently, 50 patients underwent a series of
      tests including a maximal graded exercise treadmill test, assessment of body
      composition, and fasting blood lipid analysis, at entry to CRP and after a follow
      up period that ranged from 1 to 5 years. All patients participated in a standard
      multidisciplinary cardiac rehabilitation program for 3 months. Twenty-five
      patients discontinued participation after 3 months and received no other contact
      from the program staff until follow-up, whereas 25 patients remained active in
      the program until follow-up. After statistically adjusting for baseline
      differences between the groups, significant differences were observed between the
      extended- and standard-length groups at follow-up for body weight (177 vs 183
      lbs), percent fat (22% vs 24%), METS (10.5 vs 8.4), high-density lipoprotein
      level cholesterol (44 vs 39 mg/dl), total cholesterol/high-density lipoprotein
      ratio (5.2 vs 6.1), and triglycerides (134 vs 204 mg/dl), respectively. No
      significant differences in the adjusted means were observed between the groups at
      follow-up for total cholesterol (209 vs 219 mg/dl) and low-density lipoprotein
      cholesterol (136 vs 138 mg/dl). Data from this study demonstrate the efficacy of
      extended participation in CRP on body composition, functional capacity, and blood
      lipids. Greater efforts need to be directed at retaining patients in low-cost,
      center-based maintenance programs and at extending monitoring of patients exiting
      standard length CRPs.

PMID- 8857481
TI  - Evaluation of left atrial appendage anatomy and function in recent-onset atrial
      fibrillation by transesophageal echocardiography.
AB  - Data regarding left atrial (LA) and LA appendage anatomy and function among
      patients with newly recognized atrial fibrillation (AF) who have not received
      long-term warfarin are currently unknown. To identify echocardiographic indexes
      which characterize those at increased risk for thrombus formation, we analyzed
      transesophageal echocardiographic studies in 100 consecutive patients with newly
      recognized AF (duration 2.6 +/- 0.3 week) who had not received long-term
      warfarin. Fourteen percent of patients had LA thrombi. LA thrombi were associated
      with larger LA appendages, more depressed LA appendage outflow velocities, and a
      higher prevalence of severe spontaneous LA contrast. Patients with spontaneous
      contrast had larger LA and LA appendage anatomy and lower LA appendage ejection
      velocity. Among patients presenting with their first episode of AF, greater LA
      appendage ejection and filling velocities and smaller LA and LA appendage sizes
      were seen among those with AF of <2 weeks duration compared with those with AF of
      >2 weeks. Thus, patients with recent onset AF and LA thrombi or spontaneous echo
      contrast have more dilated LA and LA appendage anatomy, and more depressed LA
      appendage systolic function. Data from patients with their first episode of AF
      suggests that AF is associated with rapid LA remodeling.

PMID- 8857482
TI  - Effects of carvedilol on systolic and diastolic left ventricular performance in
      idiopathic dilated cardiomyopathy or ischemic cardiomyopathy.
AB  - Recent evidence has shown that improvement in left ventricular (LV) systolic
      function in patients with New York Heart Association class II to III heart
      failure occurs with beta-adrenergic blocking agents. However the specific effects
      on LV diastolic function have been subjected to only limited examination. This
      study investigated the effects of the combined beta blocker/vasodilator,
      carvedilol, on systolic and diastolic LV performance in dilated cardiomyopathy.
      Thirty-six patients with New York Heart Association II to III heart failure and
      LV ejection fraction < or = 0.35 were entered into either arm of this placebo
      controlled, double-blind 4-month trial. Twenty-one subjects were entered into the
      carvedilol treatment arm and 15 patients were entered into the placebo arm in a
      3:2 ratio. Carvedilol therapy resulted in a significant improvement in LV
      ejection fraction, from 0.22 +/- 0.02 to 0.30 +/- 0.02 when compared with the
      placebo group (0.19 +/- 0.02 to 0.21 +/- 0.02 at baseline and after 4 months of
      therapy, respectively; p = 0.0001). However, no significant change in
      radionuclide parameters of LV diastolic function, including peak filling rate or
      time to peak filling rate, was observed. LV end-diastolic volume index did not
      change with carvedilol therapy, whereas end-diastolic volume index increased in
      the placebo group, although the difference between groups at 4 months was
      significant (p = 0.02). In conjunction with these changes, end-systolic volume
      index was smaller at 4 months after carvedilol treatment compared with that of
      the placebo group (p = 0.04). Thus, these results demonstrate that in moderate
      chronic heart failure, systolic LV performance improves but diastolic LV function
      does not improve when compared with placebo after treatment with carvedilol.

PMID- 8857483
TI  - Estimation of pulmonary artery pressure by spectral analysis of the second heart
      sound.
AB  - The objective of the present work was to test and validate a noninvasive method
      based on spectral analysis of the second heart sound (S2) to estimate the
      pulmonary artery (PA) systolic pressure in 89 patients with a bioprosthetic heart
      valve. The technique was compared with continuous-wave Doppler estimation of PA
      systolic pressure in these patients. The heart sounds recorded at the pulmonary
      area on the chest wall were digitized by computer. The spectra of S2 and those of
      the aortic (A2) and the pulmonary (P2) components of S2 were computed with a fast
      Fourier transform. Seven features were extracted from these spectra. The
      statistical analysis performed with the Pearson linear correlation coefficient
      showed that the best estimation of PA systolic pressure obtained by spectral
      phonocardiography (r = 0.84, SEE +/- 5.6 mm Hg, p <0.0001) was provided by the
      following equation: PA systolic pressure = 47 + 0.68 Fp - 4.4 Qp - 17 Fp/Fa -
      0.15 Fs, where Fs and Fp are dominant frequencies associated with the maximal
      amplitude of the power spectra of S2 and P2, respectively, Qp is the quality of
      resonance of P2, and Fp/Fa is the ratio of the dominant frequencies of P2 and A2,
      respectively.

PMID- 8857484
TI  - Echocardiographic score as a predictor of in-hospital cost in patients undergoing
      percutaneous balloon mitral valvuloplasty.
AB  - Percutaneous balloon mitral valvuloplasty (PBMV) is an effective means of
      palliating mitral stenosis, but it sometimes leads to adverse clinical outcomes
      and exorbitant in-hospital costs. Because echocardiographic score is known to be
      predictive of clinical outcome in patients undergoing PBMV, we examined whether
      it could also be used to predict in-hospital cost. Preprocedure echocardiographic
      scores, baseline clinical characteristics, and total in-hospital costs were
      examined among 45 patients who underwent PBMV between January 1, 1992, and
      January 1, 1994. Patients ranged in age from 18 to 71 years and had preprocedure
      echocardiographic scores that ranged from 4 to 12. Following PBMV, mean mitral
      valve area increased from 1.1 +/- 0.3 to 2.4 +/- 0.6 cm2 (p = 0.0001), and mean
      pressure gradient decreased from 18.3 +/- 5.9 to 6.7 +/- 2.7 mm Hg (p = 0.0001).
      In-hospital cost for the 45 patients ranged from $3,591 to $70,975 (mean $9,417;
      median $5,311). Univariate and multiple linear regression analyses demonstrated
      that among the variables examined, echocardiographic score (p = 0.0007), age (p =
      0.01), and preprocedure mitral valve gradient (p = 0.03) were associated with in
      hospital cost. Regression modeling suggested that every increase in preprocedure
      echocardiographic score of one grade was associated with an increase in in
      hospital cost of $2,663. Because echocardiographic score is predictive of both
      clinical outcome and in-hospital cost, we conclude that patients with elevated
      scores should be considered for alternative therapy.

PMID- 8857485
TI  - Frequency and characteristics of coronary thrombosis in the epicardial coronary
      arteries after cardiac transplantation.
AB  - We investigated at autopsy or at retransplantation the frequency and
      characteristics of coronary thrombosis in 76 cardiac allografts: 37 in place for
      < or = 2 months (early) and 39 in place >2 to 99 months (late). The 76 allografts
      were inserted in 69 patients: a single 1 in 56 patients and 2 allografts in 13
      patients, 7 of whom subsequently died and had an autopsy. An average of 140
      sections from 70 5-mm-long segments of 8 epicardial coronary arteries were
      examined from each of the 76 allografts with both hematoxylin-eosin and Movat
      pentachrome stains. Thrombus was found in only 1 coronary artery (3%) (the right
      one) of the 37 early allografts, and in 24 of 39 late allografts (61%). Of the
      latter 39 grafts, 29 (79%) had allograft vascular disease (AVD) and 24 (83%) of
      them had coronary thrombosis. Of the 312 epicardial coronary arteries (4 major
      and 4 minor) examined in the 39 late cases, 66 arteries (21%) contained thrombus.
      Of the 24 late cases with thrombus in at least 1 artery, thrombus was present in
      66 (34%) of the 192 epicardial coronary arteries examined: in 6 of the 8 arteries
      in 3 patients; in 5 arteries in 2 patients; in 4 arteries in 1 patient; in 3
      arteries in 5 patients; in 2 arteries in 6 patients, and in a single artery in 7
      patients. In all 66 arteries with thrombus (24 patients) the thrombus was longer
      than 5 mm. The thrombus in the late cases was entirely nonocclusive (mural) in 51
      (77%) of the 66 epicardial coronary arteries containing thrombus and entirely
      occlusive in 10 arteries (15%). It consisted exclusively of multiluminal channels
      in 6 arteries (9%) and combinations in 1 artery (2%). Acute myocardial infarcts
      were present in 3 patients, all of whom had occlusive thrombi. In all 10 arteries
      with occlusive thrombi, the thrombus was larger than the underlying plaque and no
      occlusive thrombi were located over ulcerated plaques. These observations
      demonstrate that thrombus is common in epicardial coronary arteries >2 months
      after cardiac transplantation.

PMID- 8857486
TI  - Estimation of left ventricular chamber and stroke volume by limited M-mode
      echocardiography and validation by two-dimensional and Doppler echocardiography.
AB  - This study has been designed to improve estimation of stroke volume from linear
      left ventricular (LV) dimensions measured by M-mode echocardiography, in
      symmetrically contracting ventricles. In experimental studies, the ratio of LV
      epicardial long/short axes "Z" is about 1.3. We measured systolic and diastolic
      epicardial long and short axes by 2-dimensional echocardiography in 115 adults
      with widely varying LV short-axis dimensions (LV end-diastolic dimension = 3.95
      to 8.3 cm). In a learning series of 23 normotensive and 27 hypertensive subjects,
      Z(diastole) was 1.3 +/- 0.1 and Z(systole) = 1.2 +/- 0.1, similar to findings in
      experimental animals. Regression equations were developed by comparing LV volumes
      by M-mode and 2-dimensional echocardiography. In a test series (65 subjects), LV
      volumes were calculated using separate regression equations for end-diastolic
      volume ([LV end-diastolic dimension] 4.765 - 0.288 x posterior wall thickness])
      and for end-systolic volume ([LV end-systolic dimension] [4.136 - 0.288 x
      posterior wall thickness]). Because the term 0.288 x wall thickness was only
      about 8% of the first term between brackets, the average wall thickness in the
      learning series was substituted in the Z-volume formulas applied to the test
      series: end-diastolic volume = (4.5 x [LV end-diastolic dimensions]2) and end
      systolic volume = (3.72 x [LV end-diastolic dimension]2). The mean relative error
      produced with this simplified method was 0.9%. in diastole and 1.4% in systole.
      Compared with Teichholz' M-mode volume method, Z-derived end-diastolic volume in
      the test series was equally well related to 2-dimensional volumes (both r =
      0.88), with a better intercept (1.5 vs -23 ml, p <0.001) and a slope closer to
      the identity line (1.1 vs 1.4). Similar results were found for systolic volumes.
      In a second test series of 1,721 American Indian participants in the Strong Heart
      Study without mitral regurgitation or segmental LV wall motion abnormalities,
      Doppler-derived LV stroke volume (70 +/- 14 ml/beat) was similarly predicted by
      the Z-derived method (r = 0.65, 70 +/- 11 ml/beat) and Teichholz formulas (r =
      0.64, 72 +/- 13 ml/beat), but Z-derived volumes had a regression line
      significantly closer to the identity line (p <0.005). Thus, LV chamber and stroke
      volumes can be determined from M-mode LV diameters over a wide range of LV sizes
      and in epidemiologic as well as clinical populations. The performance of this new
      method appears better than that obtained using the Teichholz formula, with a
      formula that is easy to handle and makes calculation of LV volumes by pocket
      calculator possible, even from limited echocardiographic studies.

PMID- 8857487
TI  - The Sir James Mackenzie Cardiological Society and the American College of
      Cardiology.
AB  - Documents have recently been discovered that detail the origin and emergence of
      the New York Cardiological Society in 1928 from an earlier local organization
      that was founded in 1926 and named in honor of the Scottish cardiologist Sir
      James Mackenzie. These documents shed light on the earliest evolution of
      antecedent societies to the present American College of Cardiology and provide
      important insight into the early professional organization of clinical cardiology
      in the United States.

PMID- 8857488
TI  - Morphological observations in the epicardial coronary arteries and their
      surroundings late after cardiac transplantation (allograft vascular disease)
AB  - Conclusions from this review, based primarily on study of 39 cardiac allografts
      in place for >2 months, but also on a study of 37 grafts in place for </=2
      months, might include the following: (1) allograft vascular disease affects all
      layers of the epicardial coronary arteries and usually the intramural coronary
      arteries in the outer one-half of the left ventricular wall; (2) the resulting
      intimal lesion is relatively uniform, consisting mainly of cellular and acellular
      fibrous tissue; it is diffuse, affecting all segments of the major and minor
      epicardial coronary arteries; (3) the degree of resulting luminal narrowing is
      similar in most 5-mm coronary segments, making coronary angiography hazardous in
      reliably predicting accurately the degree of luminal narrowing; (4) the extensive
      adventitial fibrosis and the extensive fibrous tissue infiltration of the
      subepicardial tissues probably inhibit dilation and remodeling of the epicardial
      coronary arteries and indeed may constrict them; (5) luminal narrowing of the
      epicardial coronary arteries after transplantation may be the consequence of both
      intraluminal lesions and exterior compression from the surrounding fibrous
      tissue; (6) intraluminal and intralesion thrombus is commonly observed as are
      multiluminal channels in coronary plaques, suggesting that organization of
      thrombi plays some role in the progression of post-transplant epicardial coronary
      disease; (7) the coronary lesions developing after cardiac transplantation are
      morphologically quite different in composition than those occurring in natural
      (nontransplantation) atherosclerosis; and (8) inflammatory cellular infiltrates
      are often extensive in the subepicardial tissues and the infiltrates in this area
      may be extensive even when interstitial myocardial inflammatory infiltrates are
      minimal or absent.

PMID- 8857489
TI  - Beta blockers prevent cardiac death following a myocardial infarction: so why are
      so many infarct survivors discharged without beta blockers?
AB  - Too often, infarct survivors are discharged from physician's care and/or hospital
      stay without beta-blocker therapy. This reflects concerns by physicians regarding
      precipitation of adverse effects. Ironically, many of the infarct survivors not
      receiving beta blockers could actually derive the greatest benefits from this
      treatment.

PMID- 8857490
TI  - Excimer laser angioplasty: focus on total occlusions.
AB  - This commentary reviews two studies published in the current issue of The
      American Journal of Cardiology, which provide important information about the use
      of excimer laser angioplasty for the treatment of chronic total occlusions. The
      commentary also summarizes fundamental laser mechanisms to clarify the
      shortcomings of excimer laser angioplasty--modest lumen improvement, prevalent
      vessel dissection, and troublesome restenosis--and to identify new applications
      of excimer laser technology.

PMID- 8857491
TI  - Time course of troponin I, myoglobulin, and cardiac enzyme release after
      electrical cardioversion.
AB  - The results of this study, conducted in 25 patients without myocardial
      infarction, showed that all the biologic markers of myocardial infarction, except
      the highly cardiospecific cardiac troponin I, increased in some patients after
      electrical cardioversion. These results allow us to conclude that electrical
      cardioversion, even preceded by a mechanical resuscitation of short duration,
      does not result in myocardial damage, and that cardiac troponin I is more
      accurate than creatine kinase-MB activity and creatine kinase-MB mass
      determination for the diagnosis of myocardial damage in patients who have
      undergone electrical cardioversion.

PMID- 8857492
TI  - Intravascular ultrasound assessment of plaque distribution in the ostium of the
      left anterior descending coronary artery.
AB  - Intravascular ultrasound revealed that coronary plaque is localized at the site
      opposite the segment of the left circumflex artery branching in the ostium of the
      angiographically normal left anterior descending artery.

PMID- 8857493
TI  - A two-step program of competitive bidding and physician feedback to reduce
      coronary angioplasty equipment costs.
AB  - We demonstrated that a program of competitive bidding among vendors and feedback
      to operating physicians was successful in reducing percutaneous transluminal
      coronary angioplasty equipment costs.

PMID- 8857494
TI  - Stent embolization during intracoronary stenting.
AB  - Nine patients with systemic embolization complicating intracoronary stenting
      (incidence 1.8%) are described. Although this rare complication was not
      associated with any clinical sequelae, great care should be taken to prevent this
      possibility, especially in patients with unfavorable anatomic characteristics,
      including lesions in the left circumflex artery, at bend points, and calcified
      lesions.

PMID- 8857495
TI  - Recanalization of chronic coronary artery occlusions using laser followed by
      balloon angioplasty.
AB  - Excimer laser angioplasty with adjunctive percutaneous transluminal coronary
      angioplasty of chronic coronary artery occlusions was performed using the Litvack
      1.3 Z laser catheter in 80 patients in whom the occlusion could be passed by a
      guidewire; success rate was 89%. Angiographic follow-up revealed a restenosis
      rate of 33% and a reocclusion rate of 20%, and clinical follow-up showed a
      significant symptomatic improvement. It is concluded that laser angioplasty is a
      promising method for the treatment of chronic coronary artery occlusions.

PMID- 8857496
TI  - Gender dimorphism in cardiac adaptation to hypertension is unveiled by prior
      treatment and efficacy.
AB  - The gender dimorphism in cardiac remodeling, previously recognized in primary
      hypertension, is unveiled in the group of patients with uncontrolled hypertension
      despite medical therapy. Prior antihypertensive treatment and its efficacy should
      be considered in population studies designed to evaluate the impact of left
      ventricular hypertrophy or its regression.

PMID- 8857497
TI  - Skeletal muscle hypoperfusion during recovery from maximal supine bicycle
      exercise in patients with heart failure.
AB  - Leg blood flow (LBF) and its relation to central hemodynamics were examined
      during recovery following maximal supine bicycle exercise in 11 patients with
      heart failure and 20 patients with normal exercise capacity after myocardial
      infarction. The results indicate that LBF was markedly reduced in patients with
      heart failure, and that decreased cardiac output response and enhanced peripheral
      vasoconstriction, which functioned to prevent hypoperfusion in the nonexercising
      vital regions and to maintain arterial blood pressure, were responsible for the
      reduced LBF during recovery in heart failure.

PMID- 8857498
TI  - Importance of left atrial appendage function as a risk factor for systemic
      thromboembolism in patients with rheumatic mitral valve disease.
AB  - One hundred fifty-six patients with rheumatic mitral valve disease were studied
      with transesophageal echocardiography to assess the influence of left atrial (LA)
      appendage size and contractile function on the occurrence of systemic embolism.
      LA appendage function, represented by peak emptying velocity, was found to be a
      better indicator than LA spontaneous echo contrast as a risk factor for systemic
      thromboembolism.

PMID- 8857499
TI  - Parasympathetic activity in Friedrich's ataxia.
AB  - We compared 19 patients with Friedreich's ataxia, a progressive hereditary
      neuromuscular disorder, with 19 healthy age-matched subjects. During nighttime,
      patients had shorter mean RR and decreased heart rate variability parameters
      related to parasympathetic activity than healthy subjects, whereas no difference
      occurred during daytime.

PMID- 8857500
TI  - Hemodynamic effects of acute ethanol in young adults.
AB  - Hemodynamics effects of ethanol were studied in young adults at specific
      predetermined ethanol levels of 0.025%, 0.05%, and 0.75%. Findings included a
      decrease in end-systolic wall stress (afterload) and myocardial contractility
      following ingestion of ethanol at concentrations found in "social drinking."

PMID- 8857501
TI  - Reproducibility of wall motion score and its correlation with left ventricular
      ejection fraction in patients with acute myocardial infarction.
AB  - The inter- and intraobserver variability, as well as the relation to left
      ventricular (LV) function indexes, of LV wall motion score calculated using the
      16- and 11-segment models of LV segmentation were assessed in 105 patients with
      acute myocardial infarction who were examined at 36 +/- 7 hours from onset of
      symptoms. In these patients, the use of the 16-segment model of LV segmentation
      portends to a significantly higher inter- and intraobserver reproducibility of
      segmental wall motion score than the use of the 11-segment model. In addition,
      wall motion score assessed with the more detailed 16-segment model of LV
      segmentation showed a significantly higher correlation with LV ejection fraction
      than the wall motion score assessed using the 11-segment model.

PMID- 8857502
TI  - A conversation between two cardiologists.

PMID- 8857503
TI  - Hypertriglyceridemia and elevated lipoprotein(a) are major risk factors for
      coronary events in middle-aged men.

PMID- 8857504
TI  - Modification of myocardial biopsy technique with long sheath.

PMID- 8857505
TI  - James Smith Dinning (1922-1991).

PMID- 8857506
TI  - Nickel deficiency alters liver lipid metabolism in rats.
AB  - The present investigation was designed to examine the effect of nickel deficiency
      on lipid metabolism in liver and serum lipoproteins of rats. Therefore, a study
      over two generations was conducted feeding a nickel-deficient diet containing 13
      microg/kg nickel or a nickel-adequate diet supplemented with 1 mg/kg nickel. Male
      7-wk-old pups from the second offspring were studied. Pups fed a diet poor in
      nickel tended to have lower weight gains (P < 0.15), nickel concentrations in
      liver (P < or = 0.1) and iron levels in serum (P < 0.1) than nickel-adequate
      rats. They were classified as nickel-deficient on the basis of significantly
      lower erythrocyte counts, hemoglobin concentrations, hematocrits and nickel
      concentrations in kidney compared with nickel-adequate rats. Nickel deficiency
      caused a significant triacylglycerol accumulation in liver, with greater
      concentrations of saturated fatty acids, monounsaturated fatty acids, and
      polyunsaturated fatty acids than nickel-adequate rats. Nickel deficiency had
      slight but significant effects on the fatty acid composition of liver total
      lipids and phosphatidylcholine and phosphatidylethanolamine. Moreover, nickel
      deficient rats had significantly lower activities of the lipogenic enzymes
      glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme
      and fatty acid synthase than nickel-adequate rats. Nickel-depleted pups had
      significantly higher concentrations of triacylglycerols and phospholipids in
      serum VLDL, and cholesterol in serum LDL than nickel-adequate pups. Most of these
      alterations in lipid metabolism are similar to those obtained in several iron
      deficiency studies. Because nickel deficiency also slightly compromised iron
      status, it is possible that at least some of the observed alterations are due to
      the moderate iron deficiency.

PMID- 8857507
TI  - N-(4-hydroxyphenyl)-retinamide increases lecithin:retinol acyltransferase
      activity in rat liver.
AB  - N-(4-Hydroxyphenyl)-retinamide (4-HPR; Fenretinide) is a synthetic retinoid which
      is undergoing investigation as a cancer chemopreventive agent. However, 4-HPR
      alters vitamin A kinetics and reduces the concentration of plasma retinol. We
      have conducted studies to examine the effects of 4-HPR on the activity of the
      enzyme lecithin:retinol acyltransferase (LRAT). This enzyme is implicated in the
      absorption and storage of vitamin A and is regulated, in liver, by vitamin A
      nutritional status. To determine whether 4-HPR, like retinoic acid, is able to
      induce liver LRAT activity, vitamin A-deficient rats having negligible liver LRAT
      activity were treated with single doses of 4-HPR (0.02-2.5 mg) and liver
      homogenates were assayed for LRAT activity using 3H-retinol bound to the cellular
      retinol binding protein, CRBP, as substrate. Treatment with 4-HPR resulted in a
      dose- and time-dependent increase in liver LRAT activity which reached a maximum
      at 24 h. The activity of LRAT assayed in vitro and of hepatic 3H-retinyl ester
      content determined after an in vivo pulse of 3H-retinol were highly correlated (r
      = 0.802, P < 0.0002). When vitamin A-sufficient rats were fed a 4-HPR
      supplemented diet for 30 d, LRAT activity differed significantly from control
      values in the liver (P < 0.0001) but not the small intestines. Changes in hepatic
      retinol metabolism which favor the esterification of vitamin A may be related to
      the mechanism by which 4-HPR alters vitamin A kinetics in vivo.

PMID- 8857508
TI  - A sucrose-rich diet affects triglyceride metabolism differently in pregnant and
      nonpregnant rats and has negative effects on fetal growth.
AB  - A sucrose-rich diet (SRD) causes hypertriglyceridemia in nonpregnant rats. To
      determine whether a SRD further enhances gestational hypertriglyceridemia, female
      rats were divided into the following two groups: 1) rats fed a SRD (63 g
      sucrose/100 g), and 2) rats that received the same diet except that the sucrose
      was replaced by an equal amount of cornstarch (CD). Half of the rats were mated
      and studied at d 20 of gestation. Body weight increase did not differ between
      virgin rats fed either diet, but the final body weight of pregnant rats fed SRD
      was lower than that of rats fed CD due to fewer fetuses per litter and lower
      fetal and placental weights. The SRD enhanced plasma glucose and insulin
      concentrations in virgin but not in pregnant rats; plasma triglycerides and FFA
      concentrations and the rate of triglyceride secretion into the plasma were higher
      in pregnant than in virgin rats fed SRD, but the increase in liver triglycerides
      due to SRD was higher in virgin rats. Both removal rate of a fat emulsion and
      adipose tissue lipoprotein lipase activity (LPL) were lower in virgin rats fed
      SRD than in those fed CD. They were lower in pregnant than in virgin rats fed CD.
      Placental and fetal liver triglyceride concentration and placental LPL were
      higher in rats fed SRD than in those fed CD. Both the increased triglyceride
      secretion by the liver and the decreased triglyceride removal from blood
      resulting in maternal hypertriglyceridemia may contribute to the negative effect
      of SRD on the developing fetus.

PMID- 8857509
TI  - Dietary fat and sex modify heterozygote effects of the rat fatty (fa) allele.
AB  - Rats carrying one copy of the obesity gene fa may exhibit intermediate phenotypes
      between lean (+/+) and homozygous mutants (fa/fa). Previous data suggested to us
      that fa heterozygotes may be more sensitive than wild-type rats to high fat
      diets. To test this hypothesis, we generated +/+ and fa/+ rats and fed them diets
      containing 12% or 48% energy as fat for 7 wk. Energy efficiency was significantly
      greater in males than in females and in high fat-fed vs. low fat-fed rats.
      Perirenal fat pad weights were significantly greater in males than in females, in
      high fat-vs. low fat-fed rats and in fa/+ vs. +/+ rats. Adipose and soleus plasma
      membrane calcium-ATPase concentrations were significantly lower in rats fed the
      high fat diet. This protein was also lower in soleus of fa/+ rats compared with
      +/+ rats. There were significant diet x genotype interactions such that the high
      fat diet had the greatest effect on fat pads and calcium-ATPase in fa/+ rats. The
      results of the present study show heterozygote effects of the fa allele and
      suggest that these effects may be modulated by both sex-related factors and
      dietary manipulation.

PMID- 8857510
TI  - Dietary carbohydrate type and fat amount alter VLDL and LDL metabolism in guinea
      pigs.
AB  - The effects of low/high fat diets and simple/complex carbohydrate intake on
      specific aspects of plasma VLDL and LDL metabolism were evaluated. Guinea pigs
      were fed for 4 wk two different fat/carbohydrate concentrations: 2.5/58 (g/100 g)
      or 25/29 (g/100 g) with either sucrose or cornstarch as the sole carbohydrate
      source. Intake of high fat diets resulted in higher plasma cholesterol (P <
      0.001), whereas sucrose intake resulted in higher plasma triacyglycerol (TAG)
      concentrations (P < 0.03). Intake of starch increased apolipoprotein (apo) B
      secretion rates (P < 0.001), and nascent VLDL were smaller and contained less
      TAG/apo B than particles from the sucrose-fed group (P < 0.01). Guinea pigs fed
      the starch diets had higher plasma VLDL apo B flux and faster VLDL apo B
      clearance than those fed sucrose diets (P < 0.01). In addition, more rapid VLDL
      removal from plasma in guinea pigs fed complex carbohydrate/high fat diets was
      associated with less conversion of VLDL to LDL and lower plasma cholesterol
      concentrations compared with the high fat/sucrose group (P < 0.01). Low fat
      compared with high fat intake resulted in 60% more rapid plasma LDL apo B
      fractional catabolic rates (FCR). The LDL apo B fractional catabolic rate of all
      dietary groups was inversely correlated with plasma cholesterol concentrations (r
      = -0.83, P < 0.001). These results demonstrate that in guinea pigs, low fat diets
      decrease plasma LDL cholesterol concentrations by increasing LDL turnover rates,
      and complex carbohydrates reduce plasma TAG by affecting the composition of
      nascent VLDL particles and by increasing VLDL apo B catabolism.

PMID- 8857511
TI  - Ascorbic acid deficiency reduces hepatic apolipoprotein A-I mRNA in scurvy-prone
      ODS rats.
AB  - Using the ODS rat (genotype od/od) as a model, we investigated the effect of
      ascorbic acid deficiency on the expression of the apolipoprotein A-I gene. Male
      ODS rats (7 wk old, body weight approximately 140 g) were fed a basal diet
      containing ascorbic acid (300 mg/kg) or a diet without ascorbic acid for 14 d.
      Ascorbic acid deficiency lowered the serum apolipoprotein A-I concentration. The
      apolipoprotein A-I mRNA level in the liver of ascorbic acid-deficient rats was
      lowered to about 40% (P < 0.05) of that of control rats fed sufficient ascorbic
      acid. The mRNA level in jejunum was not affected by ascorbic acid deficiency.
      Ascorbic acid deficiency did not change the transcriptional rate of the hepatic
      apolipoprotein A-I gene, suggesting that post-transcriptional regulation was
      involved in lowering the mRNA level. The low level of hepatic apolipoprotein A-I
      mRNA was restored to the control level within 3 d after the administration of
      sufficient ascorbic acid. These data indicate that ascorbic acid deficiency
      lowers serum apolipoprotein A-I concentration through lowering its mRNA level and
      subsequent depression of its synthesis in liver.

PMID- 8857512
TI  - Vitamin B-6 status indicators decrease in women consuming a diet high in
      pyridoxine glucoside.
AB  - Previous research has shown that the pyridoxine glucoside (PNG) form of vitamin B
      6 has a reduced bioavailability compared with pyridoxine, but its effect on
      vitamin B-6 status has not been assessed. Following an 8-d adjustment period,
      nine women consumed diets containing a high or low amount of PNG for 18 d each,
      in a crossover design. The high and low PNG diets provided 1.52 mg/d (8.98
      micromol/d) and 1.44 mg/d (8.57 micromol/d) of vitamin B-6, of which 27% and 9%
      was PNG, respectively. The dietary vitamin B-6 to protein ratio of both diets was
      0.017 mg/g. Urinary excretions of 4-pyridoxic acid and total vitamin B-6 were
      significantly lower (P < 0.05) during the high PNG diet period than when the low
      PNG diet was consumed. Urinary PNG excretion was equal to about 9% of the total
      PNG intake during both periods. Plasma total vitamin B-6 (P < 0.01) and red blood
      cell pyridoxal 5'-phosphate (PLP) (P < 0.05) were significantly lower when the
      high PNG diet was consumed than during the low PNG diet period. Fecal total
      vitamin B-6 excretion was significantly higher (P < 0.001) when the high PNG diet
      was consumed. Women consuming a diet containing a higher percentage of the total
      vitamin B-6 intake as PNG exhibited a decrease in vitamin B-6 status indicators,
      consistent with the reduced bioavailability of PNG demonstrated in other studies,
      equal to a loss of 15-18% of the total vitamin B-6 intake. During the
      determination of Recommended Dietary Allowances, the reduced bioavailability of
      PNG and its presence in higher amounts in some diets should be considered.

PMID- 8857513
TI  - Milk growth factors enriched from cheese whey ameliorate intestinal damage by
      methotrexate when administered orally to rats.
AB  - Currently, there are no truly effective therapies for the treatment of
      chemotherapy-induced intestinal mucositis, a debilitating side effect with a
      pathophysiology common to many chemotherapy regimens. We tested the efficacy of a
      growth factor extract derived from cheese whey against experimental intestinal
      mucositis in rats. Rats were subcutaneously injected with the chemotherapeutic
      drug methotrexate on d 1, 2 and 3 to induce severe damage in the small bowel and
      bacterial translocation across the gut. Whey extract (15 to 514 mg/d) was given
      orally for 5-12 d, starting on d 1. Controls were fed an isonitrogenous diet.
      Histological indices of villus and crypt integrity were utilized to assess
      potential efficacy of the extract. Administration of the whey extract for 5 d
      increased the villus surface length indices in the jejunum and ileum by 52% and
      56%, respectively (P< 0.001) compared with controls not receiving the whey
      extract. The crypt area index was 64% greater (P < 0.001) in the jejunum, but not
      significantly greater in the duodenum or ileum compared with controls not
      receiving whey extract. Similarly, sucrase activity was significantly higher in
      the ileum (P < 0.001) but not significantly elevated in the jejunum, whereas
      bacterial translocation (incidence and number of colonies) was significantly
      reduced compared with controls not receiving whey extract. We conclude that oral
      whey growth factor extract reduces methotrexate-induced damage in the small
      bowel, which suggests clinical applications for the treatment of intestinal
      mucositis.

PMID- 8857514
TI  - Postabsorptive and postprandial energy expenditure and substrate oxidation do not
      change during the menstrual cycle in young women.
AB  - There is little information on the effects of the menstrual cycle on the thermic
      effect of feeding (TEF) and postprandial substrate oxidation. To address these
      issues, a dose-response study was conducted in eight young women to whom test
      meals containing 0, 1046, 2092 and 4148 kJ were administered on nonconsecutive
      days, once each during the follicular phase and once during the luteal phase of
      the menstrual cycle. Postprandial energy expenditure was measured until it
      returned to base line (test duration for the 0 kJ meal was matched to duration of
      4184 kJ meal). There was no significant difference between menstrual cycle phases
      in the duration of the thermogenic response to any size meal. TEF, calculated by
      four different methods, did not differ between follicular and luteal phases, and
      a comparable dose-response was observed in both phases. Similarly, there was no
      effect of menstrual cycle phase on postabsorptive or postprandial protein, fat,
      or carbohydrate oxidation. In conclusion, postabsorptive and postprandial energy
      expenditure and substrate oxidations did not differ in young women during the
      follicular and luteal phases of the menstrual cycle.

PMID- 8857515
TI  - Biodiscrimination of the eight alpha-tocopherol stereoisomers results in
      preferential accumulation of the four 2R forms in tissues and plasma of rats.
AB  - According to the USP, 2R,4'R,8'R-alpha-tocopheryl acetate (RRR-alpha-TAc) is 1.36
      times more active than all-rac-alpha-tocopheryl acetate (all-rac-alpha-TAc). The
      all-rac form contains 12.5% each of the stereoisomers RRR, RRS, RSR, RSS, SSS,
      SSR, SRS and SRR, which display different biopotencies. In the present study,
      female rats fed a vitamin E-deficient diet were administered 0.82 mg of all-rac
      alpha-TAc or 0.60 mg of RRR-alpha-TAc daily for up to 90 d. alpha-Tocopherol
      concentrations in liver, brain, adipose tissue and plasma were not significantly
      different among groups on treatment d 64 and 90. Thus, equipotent dosages of all
      rac-alpha-TAc or RRR-alpha-TAc resulted in equimolar alpha-tocopherol plasma and
      tissue concentrations. A comparison with rats administered tocopherol-free
      placebo showed that plasma and tissue alpha-tocopherol of alpha-TAc-treated rats
      represented alpha-tocopherol uptake during the repletion period. The eight
      individual alpha-tocopherol stereoisomers in tissues and plasma were determined
      by chiral HPLC and capillary gas chromatography. Rats treated with all-rac-alpha
      TAc preferentially accumulated the four 2R alpha-tocopherol stereoisomers (15-22%
      each, sum of all 2R = 70-86%) in tissues and plasma. The remaining 14-30% were 2S
      stereoisomers with a predominance of the SRS form. In conclusion, all-rac-alpha
      TAc administration led to the presence of all eight alpha-tocopherol
      stereoisomers in rat liver, brain, adipose tissue and plasma. The four 2R
      stereoisomers including RRR-alpha-tocopherol were equally and significantly
      enriched. This confirmed that the configuration at C-2 of the alpha-tocopherol
      molecule has a major impact on stereoisomer biodiscrimination. Furthermore, the
      results are in agreement with the hypothesis that for alpha-tocopherol
      stereoisomers, biopotency differences are related to corresponding differences of
      alpha-tocopherol concentrations.

PMID- 8857516
TI  - Rat intestinal beta-carotene dioxygenase activity is located primarily in the
      cytosol of mature jejunal enterocytes.
AB  - The purposes of this study were to determine the location of beta-carotene
      dioxygenase (EC 1.13.11.21) activity within the rat gastrointestinal tract,
      within the villus and within enterocytes, and to identify the metabolites
      produced in each intestinal fraction. In Wistar female rats, maximal activity was
      detected in the cytosol (74-93% of the total cellular activity) of mature
      functional enterocytes harvested from the jejunum (67% of the intestinal
      activity). The specific activity, expressed in pmol of retinoids/(h x mg protein)
      rose from 49 +/- 3 in the stem cells to 199 +/- 12 in the mature functional cells
      (P < 0.05). Thus the intestinal beta-carotene cleavage activity might be
      regulated during the enterocyte maturation process. By using HPLC with diode
      array and radioactive detectors, retinal, and in the presence of NAD+, retinoic
      acid, were identified as the only metabolites produced. No beta-12'-, 10'-, and
      8'-apo-carotenals were detected, even when various enzyme sources were tested.
      These results suggest that the major, if not the sole, pathway for the formation
      of vitamin A from beta-carotene in the rat intestine is central cleavage.

PMID- 8857517
TI  - The epsilon-(gamma-glutamyl)lysine moiety in crosslinked casein is an available
      source of lysine for rats.
AB  - To determine bioavailability, expressed as the protein efficiency ratio (PER) and
      biological value (BV) in rats, of the epsilon-(gamma-glutamyl)lysine [epsilon
      (gamma-Glu)Lys] moiety in crosslinked proteins, we prepared heavily crosslinked
      [21.5 /micromol epsilon-(gamma-Glu)Lys/g casein] and intermediately crosslinked
      [13.6 micromol epsilon-(gamma-Glu)Lys/g casein] casein, using microbial
      transglutaminase. In Experiment 1, rats were assigned to one of four diets
      (heavily or intermediately crosslinked caseins, intact casein or non-protein
      diet) for 4 wk to evaluate the bioavailability of the epsilon-(gamma-Glu)Lys
      moiety in crosslinked casein as the sole source of dietary protein. Rats that
      were fed intact casein and the two crosslinked caseins had similar growth rates,
      PER, and BV, indicating that crosslinked caseins supported the growth of rats
      similarly to the intact casein. In Experiment 2, heavily crosslinked casein was
      added to wheat gluten-based diets in concentrations of 20 and 40 g/kg diet to
      evaluate the bioavailability of lysine in the epsilon-(gamma-Glu)Lys moiety of
      the casein as a lysine supplement for lysine-poor gluten. One of six diets
      (heavily crosslinked or intact casein diets in the two concentrations, gluten
      diet, or non-protein diet) was fed to rats for 4 wk. No significant differences
      in food intake, body weight gain, PER or BV were observed among rats fed the
      intact or crosslinked casein diets at either 2 or 4 g/100 g casein. These results
      suggest that the epsilon-(gamma-Glu)Lys moiety in crosslinked caseins are
      absorbed and therefore supplement the gluten. HPLC analysis of urine and feces of
      rats fed the crosslinked caseins actually confirmed that approximately 99% of the
      epsilon-(gamma-Glu)Lys moiety was absorbed in the body.

PMID- 8857518
TI  - Feeding rats the nitric oxide synthase inhibitor, L-N(omega)nitroarginine,
      elevates serum triglyceride and cholesterol and lowers hepatic fatty acid
      oxidation.
AB  - This study was conducted to examine whether nitric oxide regulates lipid
      metabolism. In Experiment 1, rats were fed for 5 wk diets with or without 0.2
      g/kg L-N-nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase,
      that were or were not supplemented with 40 g/kg L-arginine. Rats fed L-NNA had
      significantly higher concentrations of serum triglyceride and total cholesterol,
      lower concentrations of serum nitrate, and a lower ratio of HDL-cholesterol to
      total cholesterol than rats fed the basal diet. These alterations were suppressed
      by supplementing L-arginine to the L-NNA-containing diet. In Experiment 2, rats
      were fed diets with or without 0.2 g/kg L-NNA. Dietary L-NNA elevated serum
      concentrations of free fatty acids without affecting those of ketone bodies. L
      NNA lowered the activity of hepatic carnitine palmitoyltransferase, the rate
      limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic
      glucose-6-phosphate dehydrogenase and fatty acid synthase which are lipogenic
      enzymes. These results suggest that the lower nitric oxide level in rats fed L
      NNA leads to hyperlipidemia and that the elevation in serum triglyceride might be
      due to reduced fatty acid oxidation.

PMID- 8857519
TI  - Porcine somatotrophin differentially down-regulates expression of the GLUT4 and
      fatty acid synthase genes in pig adipose tissue.
AB  - The present study was conducted to determine whether porcine somatotropin (pST)
      differentially regulates expression of the GLUT4 and fatty acid synthase (FAS)
      genes in pig adipose tissue. Three different experiments were conducted in which
      pigs were treated daily with different doses of pST for different time periods (7
      or 14 d and from 60 to 90 kg of body wt). In these experiments, pST significantly
      and consistently decreased FAS mRNA levels (80%, 66% and 85%, respectively);
      however, GLUT4 mRNA was not affected by pST in two of the three experiments, and
      in the one showing an effect (Experiment 2), the decrease was less than observed
      for FAS (44%). Because of these results, we conducted subsequent experiments to
      see if the effects of pST on glucose metabolism in cultured pig adipose tissue
      (48 h) differed when glucose concentrations were changed from 1 to 5 mmol/L.
      These studies revealed that the antagonistic effect of pST on insulin action was
      more potent when glucose transport was saturated (5 mmol/L) than when glucose
      concentration limited glucose entry into the cell (1 mmol/L). In summary, these
      results suggest that the effects of pST on glucose transport in pig adipocytes
      are secondary to changes elicited by the hormone on intracellular glucose use for
      lipogenesis. When considered in the context of the decrease previously observed
      in glucose transport in pig adipocytes, the findings reported herein suggest that
      pST acts to decrease GLUT4 protein activity and/or distribution between the
      plasma membrane and the intracellular pool with little alteration in GLUT4 gene
      expression or total cell GLUT4 protein.

PMID- 8857520
TI  - Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs.
AB  - The early-weaned pig develops intestinal atrophy and provides a readily
      accessible animal model for determining the role of dietary supplementation of
      glutamine (Gln, a major fuel for enterocytes) in preventing intestinal damage.
      Three experiments were conducted to determine the stability of dietary Gln in the
      acidic part of the gastrointestinal tract using pigs surgically fitted with a T
      cannula in mid-duodenum (Exp. 1), and the effects of dietary Gln supplementation
      on the villus height and lamina propria depth of duodenum and jejunum (Exp. 2) as
      well as growth performance (Exp. 3) of pigs weaned at 21 d of age. Postweaning
      pigs were fed for 14 d corn- and soybean meal-based diets supplemented with 0.0,
      0.2, 0.6 or 1.0% free L-Gln. Dietary Gln was not subject to measurable acid
      hydrolysis in the stomach and upper part of duodenum and was substantially
      available for the small intestine for metabolic utilization. Glutamine
      supplementation (1.0%) prevented jejunal atrophy (as indicated by villus height)
      during the first week postweaning and increased the gain:feed ratio (an indicator
      of growth performance) by 25% during the second week postweaning. Glutamine
      supplementation (1.0%) increased plasma concentrations of aspartate, glutamate
      and alanine and reduced the extent to which plasma taurine concentration fell in
      postweaning pigs. These results provide an experimental basis for enteral use of
      Gln in swine production and clinical nutrition to prevent intestinal epithelial
      damage.

PMID- 8857521
TI  - Statistical interaction model for exchangeability of food folates in rat growth
      bioassay.
AB  - The comparative value of several sources of dietary folate in promoting growth of
      folate-depleted rats was determined in a folate depletion-repletion rat growth
      bioassay. Folate-depleted rats were fed an amino acid-based diet supplemented
      with 11 different concentrations of folate (227, 272, 317, 363, 408, 454, 499,
      544, 590, 635 and 680 nmol/kg) from each of 12 different sources of folate (folic
      acid, fried beef liver, cooked pinto beans individually, or as 1/3, 1/1, or 3/1
      combinations of folate from the folic acid/beans, folic acid/beef liver and
      beans/beef liver) for a total of 132 treatments. Growth response to folic acid
      and bean folate was linear, whereas that to beef liver folate was distinctly
      nonlinear, beef liver folate being more potent at lower dietary concentrations
      but less potent at higher concentrations compared with folic acid and bean
      folate. Folic acid and bean folate were equivalent to and exchangeable with one
      another in promoting growth. Beef liver folate and folic acid/bean folate had an
      interactive effect in promoting growth. The nature of the interaction was
      antagonistic in that the presence of folic acid and/or bean folate reduced the
      efficacy of beef liver folate and vice versa. Beef liver folate is not
      exchangeable with either folic acid or bean folate. We conclude that food folates
      generally are not exchangeable and do interact adversely. A statistical
      interaction model that predicted the growth-promoting effect of several sources
      of dietary folate was developed and validated.

PMID- 8857522
TI  - Funds for nutrition related research. Aging.

PMID- 8857523
TI  - Distrust in genetically altered foods.

PMID- 8857524
TI  - Genetic resistance spreads to consumers.

PMID- 8857525
TI  - Funding row delays Brussels BSE research.

PMID- 8857526
TI  - Funding cuts put pressure on peer review.

PMID- 8857527
TI  - Genetics and ethics in China.

PMID- 8857528
TI  - Haematopoiesis. Master regulator unmasked.

PMID- 8857529
TI  - DNA repair. A little help for my ends.

PMID- 8857530
TI  - Hyakutake's interstellar ices.

PMID- 8857531
TI  - DNA replication. Tussle with a terminator.

PMID- 8857532
TI  - Gene acquisition in HIV and SIV.

PMID- 8857533
TI  - Structure of a replication-terminator protein complexed with DNA.
AB  - The crystal structure of the Escherichia coli replication-terminator protein
      (Tus) bound to terminus-site (Ter) DNA has been determined at 2.7 A resolution.
      The Tus protein folds into a previously undescribed architecture divided into two
      domains by a central basic cleft. This cleft accommodates locally deformed B-form
      Ter DNA and makes extensive contacts with the major groove, mainly through two
      interdomain beta-strands. The unusual structural features of this complex may
      explain how the replication fork is halted in only one direction.

PMID- 8857534
TI  - Detection of acetylene in the infrared spectrum of comet Hyakutake.
AB  - Comets are rich in volatile materials, of which roughly 80% (by number) are water
      molecules. Considerable progress is being made in identifying the other volatile
      species, the abundances of which should enable us to determine whether comets
      formed primarily from ice-covered interstellar grains, or from material that was
      chemically processed in the early solar nebula. Here we report the detection of
      acetylene (C2H2) in the infrared spectrum of comet C/1996 B2 (Hyakutake). The
      estimated abundance is 0.3-0.9%, relative to water, which is comparable to the
      predicted solid-phase abundance in cold interstellar clouds. This suggests that
      the volatiles in comet Hyakotake may have come from ice-covered interstellar
      grains, rather than material processed in the accretion disk out of which the
      Solar System formed.

PMID- 8857535
TI  - Word meanings can be accessed but not reported during the attentional blink.
AB  - After the detection of a target item in a rapid stream of visual stimuli, there
      is a period of 400-600 ms during which subsequent targets are missed. This
      impairment has been labelled the 'attentional blink'. It has been suggested that,
      unlike an eye blink, the additional blink does not reflect a suppression of
      perceptual processing, but instead reflects a loss of information at a
      postperceptual stage, such as visual short-term memory. Here we provide
      electrophysiological evidence that words presented during the attentional blink
      period are analysed to the point of meaning extraction, even though these
      extracted meanings cannot be reported 1-2s later. This shows that the attentional
      blink does indeed reflect a loss of information at a postperceptual stage of
      processing, and provides a demonstration of the modularity of human brain
      function.

PMID- 8857536
TI  - Role of posterior parietal cortex in the recalibration of visually guided
      reaching.
AB  - Visually guided reaching requires complex neural transformations to link visual
      and proprioceptive inputs with appropriate motor outputs. Despite the complexity
      of these transformations, hand-eye coordination in humans is remarkably flexible,
      as demonstrated by the ease with which reaching can be adapted to distortions in
      visual feedback. If subjects attempt to reach to visual targets while wearing
      displacing prisms, they initially misreach in the direction of visual
      displacement. Given feedback about their reaching errors, however, they quickly
      adapt to the visual distortion. This is shown by the gradual resumption of
      accurate reaching while the prisms remain in place, and by the immediate onset of
      reaching errors in the opposite direction after the prisms have been removed.
      Despite an abundance of psychophysical data on adaptation to prisms, the
      functional localization of this form of sensorimotor adaptation is uncertain.
      Here we use positron emission tomography (PET) to localize changes in regional
      cerebral blood flow (rCBF) in subjects who performed a prism-adaptation task as
      well as a task that controlled for the sensory, motor and cognitive conditions of
      the adaptation experiment. Difference images that reflected the net effects of
      the adaptation process showed selective activation of posterior parietal cortex
      contralateral to the reaching limb.

PMID- 8857537
TI  - A mechanism for generation of long-range synchronous fast oscillations in the
      cortex.
AB  - Synchronous neuronal oscillations in the 30-70 Hz range, known as gamma
      oscillations, occur in the cortex of many species. This synchronization can occur
      over large distances, and in some cases over multiple cortical areas and in both
      hemispheres; it has been proposed to underlie the binding of several features
      into a single perceptual entity. The mechanism by which coherent oscillations are
      generated remains unclear, because they often show zero or near-zero phase lags
      over long distances, whereas much greater phase lags would be expected from the
      slow speed of axonal conduction. We have previously shown that interneuron
      networks alone can generate gamma oscillations; here we propose a simple model to
      explain how an interconnected chain of such networks can generate coherent
      oscillations. The model incorporates known properties of excitatory pyramidal
      cells and inhibitory interneurons; it predicts that when excitation of
      interneurons reaches a level sufficient to induce pairs of spikes in rapid
      succession (spike doublets), the network will generate gamma oscillations that
      are synchronized on a millisecond time-scale from one end of the chain to the
      other. We show that in rat hippocampal slices interneurons do indeed fire spike
      doublets under conditions in which gamma oscillations are synchronized over
      several millimetres, whereas they fire single spikes under other conditions.
      Thus, known properties of neurons and local synaptic circuits can account for
      tightly synchronized oscillations in large neuronal ensembles.

PMID- 8857538
TI  - Differentiation of adult hippocampus-derived progenitors into olfactory neurons
      in vivo.
AB  - Neurogenesis continues throughout adulthood in discrete regions. Proliferative
      zones include the subependymal zone, from where progenitors migrate along the
      rostral migratory pathway to differentiate into neurons in the olfactory bulb,
      and the hippocampal subgranular zone, where they migrate and differentiate into
      granule neurons. Progenitors isolated from adult subependymal zone exhibit in
      vitro neurogenesis when stimulated with epidermal or fibroblast growth factor.
      Cultured adult rat hippocampal progenitors (AHPs) grafted to adult rat
      hippocampus show site-specific neuronal differentiation. Here we investigate
      determinants of multipotentiality in the adult central nervous system, by
      grafting AHPs into homotypic (hippocampus) or heterotypic (the rostral migratory
      pathway) neurogenic sites or a heterotypic, non-neurogenic site (the cerebellum).
      We found that grafts into neurogenic, but not nonneurogenic sites, showed
      neuronal differentiation. Furthermore, AHPs grafted in the rostral migratory
      pathway migrated into the olfactory bulb, differentiating into tyrosine
      hydroxylase-positive neurons, a non-hippocampus phenotype. These results reveal
      that AHP populations can respond to persistent neuronal differentiation cues in
      the adult central nervous system.

PMID- 8857539
TI  - Uncoupling cadherin-based adhesion from wingless signalling in Drosophila.
AB  - The Wnt genes encode secreted glycoproteins used in intercellular communication
      at multiple steps during development. Signalling by Wingless, the Drosophila Wnt
      1 homologue, requires the activity of Armadillo, the homologue of vertebrate beta
      catenin, which is a component of the cadherin/catenin complex at adherens
      junctions. The genetic link between wingless and armadillo suggests that cell
      fate specification and cell-cell adhesion might be controlled concurrently. For
      instance, in one extreme view, Wingless could specify cell fate entirely by
      modulating cell adhesion. Alternatively, it might signal independently of
      adherens junctions. To distinguish between these alternatives, we have expressed
      two polypeptides that have opposite effects on cadherin-dependent adhesion: full
      length Drosophila E-cadherin and a dominant-negative truncated form. We found
      that overexpression of either construct mimics wingless phenotypes, thereby
      uncoupling changes in adhesion from signalling effects. We demonstrate that both
      constructs titrate Armadillo from a 'signalling' pool which is functionally
      distinct from the junctional pool.

PMID- 8857540
TI  - Nuclear import of the homeodomain protein extradenticle in response to Wg and Dpp
      signalling.
AB  - In Drosophila, Decapentaplegic (Dpp) and Wingless (Wg) are two secreted
      signalling proteins of the transforming growth factor (TGF)-beta and Wnt
      families, respectively. Although both are often required during development, only
      a few downstream components of these signalling pathways have been described.
      Here we present evidence that in the embryonic midgut both signalling pathways
      control the subcellular localization of the homeodomain protein encoded by the
      extradenticle (exd) gene. Exd protein is predominantly nuclear in endoderm cells
      close to Dpp-and Wg-secreting cells of the visceral mesoderm, but is in the
      cytoplasm in more distant endoderm cells. Both dpp and wg are required for the
      nuclear localization of Exd in the endoderm, whereas ectopic expression of dpp
      and wg expands the domain of nuclear Exd. Furthermore, the nuclear import of Exd
      correlates with the transcription of an exd-dependent reporter gene in the
      endoderm. Thus one mechanism by which extracellular signals might control pattern
      is by directing the graded nuclear localization of homeodomain proteins such as
      Exd that directly control the expression of target genes.

PMID- 8857541
TI  - Flux coupling in a neuronal glutamate transporter.
AB  - Synaptic transmission is commonly terminated by diffusion and reuptake of
      neurotransmitter from the synaptic cleft. Glutamate reuptake prevents
      neurotoxicity and sets the lower limit for the concentration of extracellular
      glutamate, so it is important to understand the thermodynamics of this process.
      Here we use voltage clamping with a pH-sensitive fluorescent dye to monitor
      electrical currents and pH changes associated with flux of glutamate mediated by
      the human neuronal glutamate transporter EAAT3. In contrast to a previous model,
      we find that three sodium ions and one proton are cotransported with each
      glutamate ion into the cell, while one potassium ion is transported out of the
      cell. This coupling can support a transmembrane glutamate concentration gradient
      ([Glu]in/[Glu]out) exceeding 10(6) under equilibrium conditions, and would allow
      the transporter to continue removing glutamate over a wide range of ionic
      conditions.

PMID- 8857542
TI  - Cyclophilin-related protein RanBP2 acts as chaperone for red/green opsin.
AB  - Cyclophilins are ubiquitous and abundant proteins that exhibit peptidyl prolyl
      cis-trans isomerization (PPlase) activity in vitro. Their functions in vivo,
      however, are not well understood. Two new retinal cyclophilin isoforms, types I
      and II, are highly expressed in cone photoreceptors of the vertebrate retina.
      Type-II cyclophilin is identical to RanBP2, a large protein that binds the GTPase
      Ran. Here we report that two contiguous domains in RanBP2, Ran-binding domain 4
      (RBD4) and cyclophilin, act in concert as a chaperone for the opsin molecule of
      the red/green-sensitive visual pigment of a dichromatic vertebrate. In
      Drosophila, the cyclophilin NinaA is expressed in all photoreceptors and is
      required for the expression of only a subset of opsins. The molecular basis of
      these photoreceptor class-specific effects and the functions of NinaA and other
      cyclophilins in vivo remain unclear. Unlike NinaA, which forms a stable complex
      with opsin from retinular cells R1-6, we find that the cyclophilin domain of
      RanBP2 does not bind opsin directly; rather, it augments and stabilizes the
      interaction between red/green (R/G) opsin and the RBD4 domain. This involves a
      cyclophilin-mediated modification of R/G opsin, possibly involving proline
      isomerization. The RBD4-cyclophilin supradomain of RanBP2, therefore, is a form
      of vertebrate chaperone of defined substrate specificity, which may be involved
      in the processing and/or transport of long-wavelength opsin in cone photoreceptor
      cells.

PMID- 8857543
TI  - Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaks.
AB  - The abundance of short and long interspersed nuclear sequences (SINEs and LINEs)
      and pseudogenes in eukaryotic genomes indicates that reverse transcriptase (RT)
      mediated phenomena are important in genome evolution. However, the mechanisms
      involved in their spread are largely unknown. We have developed a selection
      system in the yeast Saccharomyces cerevisiae to test whether RT-mediated events
      could be linked to the repair of double-strand breaks (DSBs). Here we show that
      DSBs can be fixed by the insertion of complementary DNAs at the break site. In
      the presence of functional RT (from human L1, yeast Tyl or Crithidia CRE1), and
      in the absence of homologous recombination, an HO endonuclease-induced DSB at the
      mating type (MAT) locus is the primary site at which a marked cDNA is observed
      among surviving cells. The structure and junctional sequences of these insertions
      suggest that repair occurs primarily by non-homologous recombination. Our data
      support a role for endogenous retroelements in the repair of chromosomal breaks.

PMID- 8857544
TI  - Capture of retrotransposon DNA at the sites of chromosomal double-strand breaks.
AB  - Non-homologous repair of broken chromosomes in Saccharomyces cerevisiae can be
      studied at a defined location by expressing the site-specific HO endonuclease
      that cuts the mating-type (MAT) locus. When homologous recombination is
      prevented, most double-strand breaks are repaired by non-homologous end-joinings
      similar to those observed in mammalian cells. About 1% of non-homologous repair
      events were exceptional, having 'captured' approximately 100 base pairs of DNA
      within the HO cleavage site. In each case, the insertion came from yeast's
      retrotransposon Tyl element. Four of the five contained the R-U5 region, which is
      the first part of Tyl messenger RNA to be converted to complementary DNA. The
      capture of cDNA fragments at the sites of double-strand breaks may account for
      the way that pseudogenes and long and short interspersed sequences (LINES and
      SINES) have been inserted at many locations in the mammalian genome.

PMID- 8857545
TI  - Gene transfer and therapeutic drug monitoring.
AB  - During the next decade, gene therapy will evolve from a medical curiosity into an
      essential component of medical practice. One of the elements necessary for this
      transition will be the development of simple and accurate ways of monitoring both
      the vectors used to transfer the genes of interest and the function of the genes
      themselves. This article reviews the difficulties in achieving these aims and
      describes ways in which the technology of gene transfer offers a novel means of
      monitoring current therapies.

PMID- 8857546
TI  - Individualizing therapy with 6-mercaptopurine and 6-thioguanine related to the
      thiopurine methyltransferase genetic polymorphism.
AB  - The formation of intracellular thionucleotides are a prerequisite for
      mercaptopurine (MP) cytotoxicity, and interindividual variations in the inherited
      level of thiopurine methyltransferase (TPMT) activity regulate their formation.
      Measurement of pretreatment TPMT activities can identify the TPMT "deficient"
      patient and, conversely, the individual with very high enzyme activities. The
      former are at higher risk of acute toxicity and potentially fatal bone marrow
      failure and the latter of suboptimal treatment. Leukaemic children taking MP
      therapy who form inadequate amounts of thioguanine nucleotides (TGNs) do not
      experience drug toxicity and are at an increased risk of disease relapse. When
      low TGNs are due to very high TPMT activities, thioguanine may be a more
      appropriate thiopurine. Another cause of inadequate TGN concentrations is partial
      or noncompliance with oral chemotherapy. Compliance problems can be identified by
      the measurement of both TGNs and methylated drug metabolites.

PMID- 8857547
TI  - Individualizing therapy with 5-fluorouracil related to dihydropyrimidine
      dehydrogenase: theory and limits.
AB  - 5-Fluorouracil (FU) is metabolized by dihydropyrimidine dehydrogenase (DPD).
      Patients with suspected or proven DPD deficiency develop more or less severe FU
      related side effects including death. In these reported cases, DPD activity in
      peripheral blood mononuclear cells (PBMC-DPD) was < 100 pmol/min/mg protein. A
      circadian rhythm in PBMC-DPD activity has been observed, with a peak at 1 a.m.
      and a trough at 1 p.m. on average. As a corollary, a circadian rhythm was
      observed in FU plasma concentration, with a peak at 11 a.m. and a trough at 11
      p.m. on average. A significant relationship between PBMC-DPD activity and FU
      clearance was established but the link was weak (r = 0.31). Thus, a FU dose
      adaptation based on PBMC-DPD is not justified whereas a pharmacokinetically based
      FU dose adaptation is recommended. Experimental studies have shown that DPD
      activity in tumor cell lines is related to FU cytotoxicity. Although resistance
      to FU depends on many factors, recent clinical studies in head and neck cancer
      patients treated by FU suggest that tumoral DPD activity is a determining factor
      in predicting FU-responsiveness.

PMID- 8857548
TI  - Optimizing therapy for acute myeloid leukemia based on differences in
      intracellular metabolism of cytosine arabinoside between leukemic blasts and
      normal mononuclear blood cells.
AB  - The increasing insights into the pharmacokinetics and the metabolism of
      arabinoside C (AraC) have improved the rationale for its application in leukemia
      therapy and have led to a pharmacologically directed design of antileukemic
      treatment. The current study aims at adding to this approach by detecting
      differences in the intracellular metabolism of AraC 5'-triphosphate (AraCTP)
      between leukemic and normal mononuclear blood cells. Measurements of
      intracellular AraCTP levels were complemented by determinations of plasma AraC
      and arabinoside uridine (AraU) concentrations and were performed in 26 patients
      with acute myeloid leukemia (AML) who were undergoing combination therapy,
      including high-dose (1.0 or 3.0 g/m2 x 2/day) AraC. Plasma AraC concentrations
      showed a linear relationship to the applied AraC dose but did not correlate with
      intracellular AraCTP levels. Substantial differences in AraCTP retention times
      were revealed, during 3-h infusions of either 1.0 or 3.0 g/m2 AraC in leukemic
      blasts from 10 patients with t1/2 values of 1.60-7.63 h (median, 2.42 h). In
      addition, AraCTP levels declined in only one patient by > 10% within the first
      hour after the end of therapy and remained constant or even increased up to 1.5
      fold during a posttreatment period of 1-2.5 h in the other nine cases. In
      contrast, AraCTP retention times were relatively uniform in normal mononuclear
      blood cells from 11 patients, with t1/2 values of 3.34-5.29 h (median, 3.85 h).
      More importantly, AraCTP levels dropped by > 10% within the first hour after the
      end of the high-dose AraC infusion in eight of 11 cases. A posttherapeutic
      increase of > 10% was not observed in any patient. These differences in AraCTP
      pharmacokinetics between leukemic and normal blood cells provided the basis for a
      modified timing of AraC administration with the aim of selectively maintaining
      cytotoxic AraCTP levels in leukemic blasts while allowing an intermittent drop of
      AraCTP levels in normal cells. This modification may result in higher
      antileukemic activity without increasing the damaging effect on normal cells and
      may, thus, improve the therapeutic index for AraC.

PMID- 8857549
TI  - Are the major effects of P-glycoprotein modulators due to altered
      pharmacokinetics of anticancer drugs?
AB  - Agents (modulators) that reverse the in vitro resistance of tumor cells to
      anticancer drugs that are substrates for P-glycoprotein (Pgp, the product of the
      MDR1 gene) have been given to patients concurrently with anticancer drugs in an
      attempt to improve therapeutic response. The vast majority of investigations into
      these drugs indicate that Pgp modulators decrease the systemic clearance of
      anticancer drugs, thus potentially nonselectively increasing exposure to normal
      and malignant cells and thereby potentially increasing the severity and/or
      incidence of adverse effects associated with the anticancer therapy. Mechanisms
      by which Pgp modulators could alter the pharmacokinetics of the anticancer agent
      include competition for cytochrome P450 intestinal or liver metabolism,
      inhibition of Pgp-mediated biliary excretion or intestinal transport, or
      inhibition of renal elimination. It is suggested that administration of Pgp
      modulators is unlikely to improve the therapeutic index for anticancer drugs
      unless agents that lack significant pharmacokinetic interactions are found.
      Moreover, it will likely be required that there be some cancer-tissue selectivity
      for modulators in order to avoid collaterally increasing the sensitivity of
      normal Pgp-expressing tissues to the anticancer drug.

PMID- 8857550
TI  - Mycophenolate mofetil--clinical and experimental experience.
AB  - Mycophenolate mofetil (MMF) is the first drug approved for the prevention of
      renal allograft rejection in the United States in the last 10 years. MMF is the
      morpholinoethyl ester of mycophenolic acid (MPA) and is a selective, reversible
      inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme that is
      critical for the production of guanine monophosphate. MPA is a potent inhibitor
      of IMPDH, particularly the type II isoform. Compared with other cell types,
      lymphocytes appear to be more sensitive to inhibition of the type II isoform of
      IMPDH. This decreases the metabolism of guanine nucleotides, which are necessary
      for cell function. MMF is rapidly converted to MPA, which is the
      pharmacologically active drug. MPA is highly bound to serum albumin, and recent
      evidence suggests that the pharmacologic activity of MPA is a function of the
      unbound drug. Recent studies in human clinical transplantation have demonstrated
      the efficacy of this compound in renal transplantation. A major clinical study
      with > 1,499 patients demonstrated a 50% reduction in the incidence of acute
      rejection when compared with azathioprine or placebo control. The primary side
      effects in these studies were leukopenia, gastrointestinal problems, and
      cytomegalovirus disease. MMF represents a major advance in immunosuppression for
      renal transplant recipients. Ongoing studies are being performed in other types
      of solid organ transplantation.

PMID- 8857551
TI  - Quality assessment issues of new immunosuppressive drugs and experimental
      experience.
AB  - There are established quality assessment schemes for the two immunosuppressive
      drugs that have entered routine clinical use: cyclosporine and tacrolimus. These
      two drugs, together with sirolimus and mycophenolic acid, have been the subject
      of recent consensus panel reports that have reached broad agreement on several
      issues relating to therapeutic monitoring of these agents. While the current
      quality assessment schemes are not based on validated reference methods, the data
      they yield on comparative assay performance are of value as a guide to patient
      management and for clinical studies of drug efficacy.

PMID- 8857552
TI  - Erythromycin breath test and clinical transplantation.
AB  - The intravenous 14C-erythromycin breath test (ERMBT) appears to be a convenient
      and reproducible means of measuring the activity of a major drug-metabolizing
      enzyme present in the liver, termed CYP3A4. Interpatient differences in liver
      CYP3A4 activity, as measured by the ERMBT, seem to account, for the most part,
      for interindividual differences in the kinetics of cyclosporin A and FK506. The
      predictability of the test may be improved as an oral form of the test and
      improved oral formulations of transplant medications are developed. Although the
      ERMBT is a promising research tool, its role in clinical transplantation has yet
      to be defined.

PMID- 8857553
TI  - Use of hepatic lidocaine metabolism to monitor patients with chronic liver
      disease.
AB  - Lidocaine is converted to its primary metabolic product monoethylglycinexylodide
      (MEGX) via cytochrome P-4503A4 within the liver. A steady-state concentration of
      MEGX appears in serum within 15 min following the intravenous administration of
      lidocaine. The present article reviews some of the data suggesting that this MEGX
      value can be utilized to assess hepatic function. MEGX production declines
      stepwise with the severity of chronic hepatitis. In patients with cirrhosis, MEGX
      declines further with worsening Child class. Nearly all persons with MEGX of < 20
      ng/ml had cirrhosis confirmed upon histologic evaluation. Severe life-threatening
      complications of cirrhosis were observed only in patients with MEGX production
      below 20 ng/ml. One-year survival for patients with an MEGX value of < 10 ng/ml
      was only 50%. In contrast, 1-year survival for patients with MEGX of > 10 ng/ml
      was approximately 80%. These data suggest that MEGX could be utilized as an
      accurate test of hepatic function and to predict morbidity and mortality related
      to complications of chronic liver disease. However, this test does have several
      limitations. There is wide interpatient variability between MEGX and hepatic
      histology, which severely impairs the ability of this test to accurately predict
      hepatic histology. In addition, MEGX is affected by gender and several
      medications. However, since MEGX does decline stepwise with advancing histology
      in any given patient, the available data suggest that serial monitoring of MEGX
      could be utilized to track hepatic metabolic capacity in patients with chronic
      hepatitis and cirrhosis.

PMID- 8857554
TI  - Prognostic value of the monoethylglycinexylidide test in pediatric liver
      transplant candidates.
AB  - The objective of this prospective study was to assess the prognostic value of
      dynamic and static liver function tests and clinical symptoms in pediatric
      patients with chronic end-stage liver disease in a serial examination including
      three evaluations at 3-month intervals. Of the 24 patients entering the study,
      six were given transplants within the observation period of 10 months. Of the
      remaining 18 patients who were considered in the final evaluation, five died
      before transplantation was possible. The variables included in the analysis were
      monoethylglycinexylidide (MEGX) formation from lidocaine, bilirubin, albumin, and
      creatinine serum concentrations, catalytic serum concentration of cholinesterase
      (CHE), prothrombin time (PT), factors II and V, serum amino acids, body weight,
      and presence of ascites. In nonsurvivors (n = 5), MEGX serum concentrations 30
      min after intravenous administration of lidocaine (1 mg/kg body weight) were < 10
      micrograms/L at the first examination. Statistically significant differences
      between nonsurvivors and survivors were observed for initial MEGX test results (p
      = 0.0089) and serum bilirubin concentrations (p = 0.009), as well as for the last
      available MEGX and bilirubin data from each patient (p = 0.017 and 0.016,
      respectively). At a diagnostic sensitivity of 100%, the corresponding diagnostic
      specificities for MEGX and bilirubin from the first examination were 77 and 62%,
      respectively. These data show that consistently low MEGX test results < 10
      micrograms/L, obtained 30 min after intravenous administration of lidocaine (1
      mg/kg body weight), are a prognostically unfavorable sign in pediatric transplant
      candidates.

PMID- 8857555
TI  - The use of the lidocaine-monoethylglycinexylidide test in the liver transplant
      recipient.
AB  - The lidocaine-monoethylglycinexylidide (MEGX) test is used to monitor liver
      function in liver transplant recipients. Serial studies have been undertaken
      after 155 allografts. The initial MEGX concentration is significantly correlated
      with the donor MEGX concentration. It is also influenced by the recipient's
      pretransplant bilirubin concentration, being lowest among patients with very high
      bilirubin levels. Use of segmental grafts is also accompanied by low MEGX
      concentrations. The flow-dependent clearance of lidocaine makes it a sensitive
      indicator of disturbed liver blood flow, with decreased MEGX concentrations
      occurring in hepatic artery thrombosis and rejection and as a result of cardiac
      failure and pulmonary effusions. Significant hepatic ischemia resulting in
      delayed initial function or cholestasis also is associated with low MEGX
      concentrations. The initial median MEGX concentrations were lowest among patients
      who required retransplantation or who died within 2 months of allografting.

PMID- 8857556
TI  - Stereoselectivity in drug metabolism and action: effects of enzyme inhibition and
      induction.
AB  - Many synthetic drugs that contain a chiral center are marketed as racemates.
      Taking into account the composite nature of chiral rugs has improved our
      understanding of the dose/effect relationship of these compounds. It is widely
      accepted that drug metabolism is often responsible for stereoselective
      disposition and hence factors modulating the activity of drug-metabolizing
      enzymes can modify this effect. The present article highlights the influence of
      some of these factors (induction and inhibition of drug-metabolizing enzymes) on
      stereoselective drug disposition. The latter topic includes an
      enantiomer/enantiomer interaction that alters drug disposition and drug action.

PMID- 8857557
TI  - Drug-metabolizing enzymes and therapeutic drug monitoring in psychiatry.
AB  - The multiplicity of the drug-metabolizing cytochrome P450 system was discovered
      20 years ago. During the past 10 years the complementary DNAs of the most
      important P450 enzymes have been cloned and sequenced, and much has been learned
      about their substrate specificities, selective inhibitors, and functional
      characteristics. Cytochrome P4501A2 (CYP1A2), CYP2C19, CYP2D6, and CYP3A4 are the
      most important P450s catalyzing the biotransformation of psychotropic drugs.
      Assessment of the activity of individual P450 enzymes makes it possible to
      forecast an appropriate initial dose in a patient. At present, this strategy can
      be recommended only for CYP2D6 before treatment with tricyclic antidepressants
      and certain neuroleptics. Important drug-drug interactions can be predicted if
      two substrates or a substrate and an inhibitor of a particular P450 are co
      administered. Therapeutic drug monitoring is of invaluable help in discovering
      and handling this type of interaction.

PMID- 8857558
TI  - Drug metabolism in liver disease: implications for therapeutic drug monitoring.
AB  - Over the last decades, a bulk of evidence has accumulated on the effect of liver
      disease on drug metabolism. It has convincingly been demonstrated that liver
      disease is associated with a reduced metabolic capacity with respect to drugs
      undergoing oxidative biotransformation, whereas conjugation reactions, especially
      glucuronidation, seem less affected. Nevertheless, many data have been
      conflicting, and it has become increasingly clear that differences in patient
      selection and severity of disease can account for these. Further, more recent
      communications suggest that liver disease led to a differential alteration of the
      cytochrome P-450s with regard to protein content and activity. From a clinical
      point of view, these findings may have important implications. However, when
      treating liver patients, we still have no generally accepted model for dose
      predictions; the best approach should be empiric and based on the clinical
      response. In selected cases, monitoring of plasma drug concentrations and liver
      function is recommended.

PMID- 8857559
TI  - Overview of therapeutic drug monitoring and biotechnologic drugs.
AB  - Therapeutic drug monitoring (TDM) is the science that combines measurement of
      serum drug concentrations with clinical pharmacokinetics. Biotechnological drugs
      may be obtained by recombinant DNA technology, monoclonal antibody technology,
      polymerase chain reaction, gene therapy, nucleotide blockade, peptide technology,
      and carbohydrate technology. Examples of biotechnological drugs include antisense
      drugs, clotting factors, hematopoietic factors, hormones, interferons,
      interleukins, monoclonal antibodies, tissue growth factors, and vaccines. For
      drugs that are physiological peptides used for substitution therapy, TDM is not
      indicated. For other biotechnological drugs, the criteria developed for
      monitoring of "classical" therapeutic agents should be used on an individual
      basis to determine whether there is a role for TDM.

PMID- 8857560
TI  - Immunoassays in monitoring biotechnological drugs.
AB  - For the evaluation and interpretation of pharmacokinetic data reliable
      quantitative determinations are a requirement that can only be met by well
      characterized and fully validated analytical methods. To cope with these
      requirements a method is being established that is based on an integrated and
      automated fiber-optic biospecific interaction analysis system (FOBIA) for
      immunoassays. Performance characteristics of this system used in monitoring of
      recombinant hirudin (CGP 39 393) are presented. Recombinant hirudin is a highly
      potent and selective inhibitor of human thrombin. Owing to its size and charge,
      recombinant hirudin is mainly eliminated by glomerular filtration. But only a
      fraction of the hirudin dose seems to be reabsorbed at the proximal tubule by
      luminal endocytosis and hydrolyzed by lysosomal enzymes, leaving approximately
      50% of the dose to be extracted in the urine. Thus, renal clearance of
      recombinant hirudin in the absence of renal insufficiency appears to depend
      primarily on the glomerular filtration rate. During a 3-month i.v. tolerability
      study in dogs, some of the dogs developed antibodies against recombinant hirudin.
      The hirudin-antibody complex accumulated in plasma and apparent hirudin plasma
      concentrations were therefore much higher than expected from single-dose
      kinetics. Hirudin captured by antibodies showed an extended half-life and the
      hirudin-antibody complex is still pharmacologically active, as demonstrated by
      the observed increase in thrombin time. In conclusion, only appropriate
      analytical methods allow adequate monitoring and pharmacokinetic characterization
      of biotechnology drugs in biological materials.

PMID- 8857561
TI  - Cardiovascular gene therapy: current concepts.
AB  - Gene therapy techniques are under development for many areas of medicine,
      including cardiovascular disease. Identifying appropriate gene targets will
      require more detailed knowledge of the molecular pathophysiology of these
      disorders, and choosing appropriate vectors and delivery systems will contribute
      significantly to the challenge of developing this approach for clinical use. The
      concepts of toxicology and therapeutic drug monitoring will need to be broadened
      to account for the unique chemical, biological, and genetic characteristics of
      gene therapeutic agents. This review will provide an overview of strategy
      development, currently available vectors, and examples of their application to
      cardiovascular gene transfer. Considerations of the potential toxicities
      associated with particular vectors and delivery systems, as well as the types of
      genetic modifications possible, will provide some guidelines regarding
      appropriate monitoring of their clinical application.

PMID- 8857562
TI  - Role of pharmacokinetic-pharmacodynamic principles in rational and cost-effective
      drug development.
AB  - An important goal of drug development is to define dose and concentration
      response relationships for new drugs and biologics. Such critical information
      from controlled clinical trials can provide primary evidence of efficacy and
      safety and an informative database for devising dosing instructions for clinical
      use. This article describes applications of pharmacologic principles
      [pharmacokinetic-pharmacodynamic (PK-PD)] and modeling methods for drugs in which
      the evaluation process is guided by and/or identifies significant PK and/or PD
      variability in drug response. In the case of the recently registered
      immunosuppressive agent, tacrolimus, preclinical PK-PD in model systems can be
      used to rationally design safe and effective immunomodulatory dosing regimens for
      phase 1 clinical studies. Furthermore, a study design based on concentration
      control guided by a novel artificial intelligence modeling system (AIMS) can be
      efficiently applied to conduct randomized clinical trials in auto-immunity and to
      implement cost-effective therapeutic drug monitoring of tacrolimus and
      cyclosporine in clinical transplantation. In the case of a cardioselective beta
      adrenergic blocking agent, betaxolol, marketed for essential hypertension,
      population PD modeling can be shown to be a more efficient method for estimating
      dose response compared with standard statistical tests. Using a sigmoid Emax PD
      model, only a fraction (40 of 300) of the randomized patients was needed to
      demonstrate dose response. Therefore, two methods, i.e., PD modeling of dose
      response and AIMS-guided dosing, can achieve significant cost benefits for drug
      developers, patient care, and the health care system.

PMID- 8857563
TI  - Clinical development of a cyclosporine microemulsion in transplantation.
AB  - Current clinical difficulties in the use of cyclosporine in transplantation are
      in part due to its narrow therapeutic window between effective immunosuppression
      and adverse events and in part due to suboptimal absorption associated with wide
      pharmacokinetic variability. Under the assumption that the latter aspects are
      largely formulation-related, a clinical development program was undertaken to
      compare the conventional formulation (Sandimmun) with a new microemulsion
      preconcentrate (Neoral). After oral administration, Neoral immediately forms a
      microemulsion in aqueous gastrointestinal fluids yielding a homogeneous
      dispersion from which cyclosporine is more readily absorbed. Single-dose
      crossover studies in healthy subjects were initially performed to document
      improved bioavailability and dose linearity, lower intrasubject pharmacokinetic
      variability, and reduced food effect with Neoral. In a subsequent phase of the
      development program, questions that could only be assessed in transplant patients
      at steady state were addressed in small, open-label studies under a trough
      concentration-guided strategy. This approach was necessary to maintain effective
      immunosuppression while determining appropriate and safe guidelines for
      converting between formulations, assessing the trough: area under the curve
      correlation and exploring for potential differences in metabolism. Multicenter,
      double-blind, randomized investigations were then performed to compare the
      formulations in stable and de novo transplant populations. In this context, the
      conversion approach, the safety/tolerability profile, and the attendant
      pharmacokinetic advantages of the microemulsion formulation were confirmed in
      larger populations under clinical conditions. It is anticipated that the more
      precise pharmacokinetic control possible with Neoral will provide a firmer base
      from which to elucidate the relationship between cyclosporine exposure and graft
      survival to optimize cyclosporine-based immunosuppressive regimens.

PMID- 8857564
TI  - Computer-guided randomized concentration-controlled trials of tacrolimus in
      autoimmunity: multiple sclerosis and primary biliary cirrhosis.
AB  - A randomized concentration-controlled clinical trial (RCCCT) is a trial design in
      which patients are randomized to predefined blood drug concentrations (low,
      medium, high). If the concentration ranges are sufficiently separated, this study
      design can reveal important blood concentration-response relations. Tacrolimus is
      a potent yet "infant" immunosuppressant for the treatment and prevention of graft
      rejection and has been shown to exhibit significant clinical activity in some
      immune-mediated disorders. A tacrolimus artificial intelligence modeling system
      (AIMS) was used to guide patient dosing to achieve target concentrations
      specified by the study protocols. In the Multiple Sclerosis study group, we were
      able to define a concentration range (0.3-0.7 ng/ml) that appeared to show
      efficacy and minimal tacrolimus toxicity. Patients randomized to the high zone
      (0.6-1.2 ng/ml) in the Primary Biliary Cirrhosis study group showed significant
      reduction (approximately 50%) in surrogate efficacy markers [aspartate
      aminotransferase (SGOT), alanine aminotransferase (SGPT)] compared with patients
      in the low zone (0.1-0.6 ng/ml). Therefore the RCCCT allowed the detection and
      delineation of clinically significant concentration-response relations in an
      ethical and efficient manner.

PMID- 8857565
TI  - Mechanisms of drug incorporation into hair.
AB  - Hair testing for drugs of abuse is a developing technology that offers the
      possibility of longer detection times than is commonly obtained with urine or
      blood analysis. There are many uncertainties concerning how drugs enter hair and
      factors that affect drug deposition and residence in hair. Possible routes of
      drug entry include diffusion from blood, sweat, sebum, and skin and entry from
      the environment. Evidence is reviewed regarding the importance of each of these
      routes as possible contributors to drug deposition in hair. Binding to specific
      sites in hair may involve both electrostatic forces and weaker attractions, such
      as van der Waals forces. Melanin and protein constituents of hair may serve as
      binding sites. Recent in vitro studies suggest that the color of hair or melanin
      content may be the major determinant of cocaine binding and, consequently, may
      result in color or ethnic bias in hair testing.

PMID- 8857566
TI  - Hair analysis as evidence in forensic cases.
AB  - The analysis of hair for drugs of abuse is a powerful tool useful in answering
      questions that cannot be solved by the detection of drugs in body fluids, e.g.,
      blood, urine, or saliva. The most frequent forensic investigations occur in cases
      where narcotics laws are offended and in questions of criminal responsibility
      where the chronic use of a drug is an issue. In the list of drugs of abuse,
      heroin, cocaine, amphetamine, and cannabis are the drugs of abuse that are most
      frequently involved in judicial inquiries.

PMID- 8857567
TI  - Drug testing in addicts: a comparison between urine, sweat, and hair.
AB  - The standard in drug testing is the immunoassay screen, followed by a gas
      chromatography/mass spectrometry confirmation conducted on a urine sample.
      Recently sweat and hair analyses were proposed for identifying drug abusers.
      Specimens can be collected under close supervision without embarrassment and are
      not subject to evasive maneuvers. In contrast with urine, hair analysis has a
      wide window of detection, ranging from months to years, and provides information
      concerning the severity and pattern of an individual's drug abuse. Testing
      individuals for illicit drugs with sweat patches worn continually would provide
      effective coverage for a week. Studies conducted in a detoxification center have
      shown that hair analysis is more sensitive for detecting illicit drug use than is
      urine screening. My experience in drug testing is discussed in the light of the
      existing literature.

PMID- 8857568
TI  - Judicial acceptance of hair tests for substances of abuse in the United States
      courts: scientific, forensic, and ethical aspects.
AB  - Changes in the acceptance of hair test results in the United States courts have
      resulted from two factors: the rapidly evolving scientific understanding of hair
      test data; and modification of the admissibility standards for forensic evidence
      in United States courts. The scientific, forensic, and ethical aspects of drug
      testing in hair impact the acceptance of hair test results. Our knowledge and
      experience with this new analytical technology have been developing rapidly,
      although there are many unanswered questions that influence acceptance of data. A
      consequence of the recent U.S. Supreme Court decision to have the Federal Rules
      of Evidence take precedence over the Frye standard in the admissibility of
      scientific evidence has enabled judges to determine if evidence will assist in
      obtaining a fuller understanding of a given case. A summation of the scientific,
      forensic, and ethical aspects of judicial acceptance of hair test results may be:
      If hair test results are positive, have we proven beyond a reasonable doubt
      and/or demonstrated that the preponderance of evidence supports a finding of drug
      use? In general, recent court decisions indicate that hair test results provide
      information that the courts should consider. However, unresolved scientific,
      forensic, and ethical issues may have a greater effect on the weight applied to
      hair test evidence rather than its admissibility in future court proceedings.

PMID- 8857570
TI  - On the metabolism and the toxicological analysis of
      methylenedioxyphenylalkylamine designer drugs by gas chromatography-mass
      spectrometry.
AB  - Designer drugs of the methylenedioxyphenylalkylamine type are increasingly
      abused. Studies on their metabolism in humans are necessary to develop a reliable
      gas chromatography--mass spectrometry (GC-MS) screening procedure. Such a method
      must allow their detection in urine for drug testing in clinical and forensic
      toxicology. Studies on racemic methylenedioxyamphetamine (MDA),
      methylenedioxymetamphetamine (MDMA), methylenedioxyethylamphetamine (MDE),
      benzodioxazolylbutanamine (BDB), and N-methylbenzodioxazolylbutanamine (MBDB) are
      presented. The metabolites were identified by GC-MS after enzymatic hydrolysis,
      isolation (pH 4.5 and 8-9), and derivatization (acetylation followed by
      methylation). The drugs undergo two overlapping metabolic pathways: O
      dealkylation of the methylenedioxy group to dihydroxy derivatives followed by
      methylation of one of the hydroxy groups and successive degradation of the side
      chain to N-dealkyl and deaminooxo metabolites. MDA, MDMA, and MDE are
      subsequently metabolized to glycine conjugates of the corresponding 3,4
      disubstituted benzoic acids. The hydroxy metabolites are excreted in a conjugated
      form. Based on these results, a GC-MS procedure was developed for simultaneous
      screening and identification of these designer drugs and/or their metabolites in
      urine after acid hydrolysis, isolation at pH 8-9, and acetylation. With use of
      mass chromatography with the most characteristic fragment ions m/z 58, 72, 86,
      150, 162, 164, 176, and 178, the presence of the designer drugs was indicated and
      the peak underlying spectra could be identified by computerized comparison with
      reference spectra recorded during the presented studies. The procedure was
      suitable to detect an abuse of or an intoxication with the studied designer drugs
      (detection limit 5-50 ng/ml).

PMID- 8857569
TI  - Alcohol plus cocaine: the whole is more than the sum of its parts.
AB  - Cocaethylene, an active metabolite that arises through hepatic
      transesterification of cocaine when cocaine and ethanol are used together, shares
      many neurochemical and pharmacological properties with cocaine. Cocaethylene is
      similar to cocaine in its properties as an indirect dopamine agonist, and human
      subjects cannot distinguish its effects from those of cocaine. Cocaethylene, and
      especially its isopropyl analog, are more selective indirect dopamine agonists
      than cocaine, with relatively weak potency at the serotonin transporter.
      Cocaethylene may contribute to the manifestations and consequences of combined
      cocaine and ethanol use, although its relative importance remains unclear.

PMID- 8857571
TI  - Doping control in sports medicine.
AB  - Doping control has become one of the strongest measures to reduce the impact of
      doping in sports. The rationale for doping control is based on the need to
      maintain both ethical and medical principles. Among the banned pharmacological
      substances, the most relevant to sports medicine are anabolic agents, stimulants,
      narcotic, peptide hormones, diuretics, masking agents, and adrenergic beta
      blockers. Optimized use of state-of-the-art analytical methodology and suitable
      quality control mechanisms warrant reliability in the laboratory. Adequate
      interpretation of results requires knowledge of pharmacology, toxicology, drug
      metabolism, and pharmacokinetics. The detection and confirmation of doping using
      endogenous substances are especially difficult for urine testing. The alteration
      caused in indirect markers in other biological materials, such as blood, will be
      the focus of further developments in the field.

PMID- 8857572
TI  - Quality in environmental toxicology measurements.
AB  - From the clinical chemist's point of view, environmental toxicology can be
      defined as the identification or quantitation or both of environmental toxicants,
      their metabolites, and the biochemical consequences in easily accessible human
      specimens. Requirements as to specificity, accuracy, precision, and sensitivity
      will vary depending on the purpose of the analysis (e.g., diagnosis of acute
      intoxication vs. population baseline study). Laboratories must therefore clearly
      indicate the scope of their analytic methods. To ensure consistency of results,
      quality guidelines, such as International Standards Organization (ISO) guide 25,
      should be adhered to. However, to demonstrate accuracy, external proficiency
      assessment is required. Interlaboratory comparison programs, by using
      representative reference material, can document laboratory performance over time.
      Examples taken from the Quebec Toxicology Centre's program for toxic metals in
      biologic fluids indicate that laboratory performance has improved in recent
      years. The quality of results is generally adequate for most applications of
      environmental toxicology measurements.

PMID- 8857573
TI  - Thin-layer chromatography: a neglected technique.
AB  - Thin-layer (or planar) chromatography (TLC) is critically reviewed from the point
      of view of drug analysis in biological fluids. The capabilities of the various
      techniques of TLC are described and their advantages and disadvantages are
      discussed. An example of the use of high-performance TLC with scanning
      densitometry for the quantitative determination of antipyrine in human plasma is
      provided. The use of TLC-mass spectrometry and TLC-tandem mass spectrometry,
      directly from the sorbent, in the identification of the compounds separated by
      TLC is discussed.

PMID- 8857574
TI  - Molecular aspects of design of immunoassays for drugs.
AB  - An understanding of the molecular structure of the antibody binding site, the
      epitope complementary to the antibody, and the intermolecular forces that
      determine the affinity and specificity of the interaction of antibody and epitope
      is fundamental to the design of immunoassays. This is particularly important for
      haptens because their small size results in small changes in substituent
      functional groups, e.g., optical rotation and carboxyl substitution for amide
      resulting in large changes in binding affinity. It should be possible to predict
      the effect of haptenic structure on binding affinity by considering the resulting
      changes in balance between the different intermolecular forces. This information
      can be used in designing immunogens and modifying the reaction conditions used
      during assay optimization, such as pH or ionic strength, that enhance the
      predominant intermolecular forces to increase the binding affinity but leave
      minimal matrix effects. Improved understanding of the molecular aspects of the
      immunological interaction can facilitate more rapid and economic immunoassay
      development.

PMID- 8857575
TI  - Nuclear magnetic resonance and high-performance liquid chromatography-nuclear
      magnetic resonance studies on the toxicity and metabolism of ifosfamide.
AB  - A combination of high-resolution nuclear magnetic resonance (NMR) and high
      performance liquid chromatography (HPLC)-NMR spectroscopic methods has been used
      to analyse urine from humans and rats treated with the anticancer drug
      ifosfamide. It was possible to detect a range of abnormal endogenous metabolites
      in urine after ifosfamide administration to human subjects undergoing cancer
      therapy and to relate the metabolic perturbations to the nephrotoxic effects of
      the drug. Changes observed by 1H NMR included increases in levels of urinary
      glucose, glycine, alanine, histidine, lactate, acetate, succinate, and
      trimethylamine-N-oxide and decreases in the levels of hippurate and citrate.
      Additional evidence was gained that ifosfamide-induced nephrotoxicity might be
      related to the level of oxidation of the coadministered drug mesna. By using both
      directly coupled continuous-flow 31P HPLC-NMR spectroscopy to determine the
      retention times of the phosphorus-containing metabolites and, subsequently, stop
      flow 1H HPLC-NMR of the urine, it was possible to isolate and identify on-line
      the metabolites ifosfamide mustard, 4-hydroxy-ifosfamide, 2
      dechloroethylifosfamide, and the parent compound itself. These studies illustrate
      the potential of combining 1H NMR spectroscopy of biofluids and HPLC-NMR
      spectroscopy for the investigation of drug metabolism and toxicity in humans and
      animals.

PMID- 8857576
TI  - Capillary electrophoresis for drug analysis in body fluids.
AB  - Capillary zone electrophoresis (CZE) and micellar electrokinetic capillary
      chromatography (MECC) represent attractive methods for the determination of drugs
      and metabolites in body fluids. In CZE, minute (nanoliter) quantities of samples
      are applied to the beginning of a fused-silica capillary filled with buffer. On
      application of a high-voltage DC field, charged solutes begin to separate and are
      swept through the capillary by the combined action of electrophoresis and
      electroosmotic bulk flow and are on-column detected toward the capillary end. In
      MECC, the buffer contains charged micelles (e.g., dodecyl sulfate micelles) and
      both uncharged and charged solutes separate based on differential partitioning
      between the micelles and the surrounding buffer and, if charged, also by
      differential charge effects, including electrophoresis. Based on validated MECC
      drug assays developed in our laboratory, key aspects of measuring drug levels by
      MECC, including sample preparation, solute detection and identification,
      quantitation, reproducibility, and quality assurance are discussed. Drug levels
      determined by MECC are shown to be in good agreement with those obtained by
      nonisotopic immunoassays and/or high-performance liquid chromatography (HPLC).
      Using on-column multi-wavelength detection, this technology is also well suited
      for toxicological drug screening and confirmation and for the exploration of drug
      metabolism. Compared with HPLC and gas chromatography, capillary electrophoresis
      has distinct advantages, including automation, small sample size, minimal sample
      preparation, use of very small amounts of organic solvents and inexpensive
      chemicals, ease of buffer change and method development, and low cost of
      capillary columns. Electrokinetic capillary assays are complementary to the
      widely employed immunoassays. The state of the art and the pros and cons of
      capillary electrophoresis for the determination of drugs in body fluids are
      discussed with the goal of encouraging newcomers to start using this emerging
      analytical methodology.

PMID- 8857577
TI  - Evaluation of the effect of the fenbendazole sustained-release intraruminal
      device on the immunity of calves to lungworm.
AB  - Each of 10 set-stocked calves was given a fenbendazole sustained-release
      intraruminal bolus at turnout for the control of parasitic bronchitis while a
      group of 10 similar calves was left untreated. The respiratory rates of the
      control calves were not greatly increased during the grazing season, but
      persistent coughing was evident from early July when they all had patent lungworm
      infections. Only occasional coughing was reported from the bolus-treated calves
      except for a transient increase in its frequency in late September. In mid
      August, one of the treated calves was passing lungworm larvae and when they were
      housed six of the 10 had patent infections. In August tracer calves picked up an
      average of 23.5 lungworms per day from the control paddock but only 2.1 from the
      paddock grazed by the treated calves. In September the corresponding figures were
      7.6 and 19.2 lungworms per day, respectively, from the control and 'treated'
      paddocks. After housing, the post mortem worm counts after an experimental
      challenge with Dictyocaulus viviparus larvae were reduced by 99.2 and 98.7 per
      cent (P < 0.0001), respectively, for the control and bolus-treated calves in
      comparison with weight-matched parasite-naive calves. Thus, despite a relatively
      low level of challenge during the grazing season, the treated animals had
      developed a considerable degree of protective immunity.

PMID- 8857578
TI  - Risk factors for perinatal and postnatal mortality in lambs.
AB  - Factors associated with preweaning mortality in lambs were identified by
      developing risk profiles with logistic regressions for perinatal and postnatal
      mortality. Compared with heavy lambs, lambs of low birth weight had almost twice
      the risk of perinatal mortality (odds ratio [OR] = 1.9) and lambs of average
      weight had a slightly lower risk (OR = 0.7). Two of four lambing location
      categories affected perinatal mortality, with lambs born at unmonitored areas at
      greatest risk (OR = 2.7). Multiple births increased the risk of perinatal
      mortality (OR = 1.5), especially among Targhee lambs (OR = 4.0). Breed variations
      in perinatal mortality were significant in Suffolk lambs (OR = 1.9) and Booroola
      Rambouillet lambs (OR = 2.1). Lambs born weak had an increased risk of postnatal
      mortality while strong lambs had a decreased risk (OR = 3.7 and 0.6,
      respectively) if the dam had an adequate milk supply. Poor milk supply increased
      the risk of postnatal mortality for lambs of average vigour (OR = 3.3), but did
      not change the risk for weak or strong lambs. Male lambs castrated at 30 days of
      age were at less risk of postnatal mortality (OR = 0.3) than females. There were
      slight increases in the risk of postnatal mortality for intact males (OR = 1.3),
      low birth weight lambs (OR = 1.6), and lambs born in sheds (OR = 1.3). Suffolk
      lambs (OR = 1.8) and Targhee lambs (OR = 1.6) had a higher risk of postweaning
      mortality.

PMID- 8857579
TI  - An attempt to reproduce 'mal seco' in horses by feeding them Festuca argentina.
AB  - 'Mal seco' is an almost invariably fatal disease of horses in Argentina and
      Chile, which resembles grass sickness, a dysautonomia of horses in Europe. The
      aetiology of mal seco remains unknown. An attempt to reproduce the disease was
      made by feeding horses with Festuca argentina, a plant considered to be toxic to
      animals and which was consistently found in the diet of nine horses suffering
      from mal seco. Three horses were fed with F argentina ad libitum for 28 days. The
      plant was infected with an endophytic fungus, whose morphological characteristics
      were in agreement with descriptions of Acremonium chlamydosporioides. No clinical
      abnormalities were observed in two of the horses, but one died on the fifth day
      of the trial after becoming incoordinated, unsteady and ataxic in the fore- and
      hindlimbs. No gross changes were observed post mortem in any of the horses, with
      the exception of a small number of Fasciola hepatica in the liver of the horse
      which died, and a moderate number of Gasterophilus species in the stomach of all
      three horses. No histopathological changes were observed in any of the organs
      examined, including several autonomic ganglia, brain including most brain stem
      nuclei, spinal cord, liver, kidney, stomach and small and large intestine. The
      results of this study suggest that F argentina is either not implicated in the
      aetiology of mal seco or produces its effects only when they are triggered by
      other unknown factors.

PMID- 8857580
TI  - Animal reservoirs of Escherichia coli O157:[H7].

PMID- 8857581
TI  - Use of a related ELISA antigen for efficient TRT serological testing following
      live vaccination.

PMID- 8857582
TI  - Time spent by turkeys in transit to processing plants.

PMID- 8857583
TI  - Flexion tests during horse-purchase examination.

PMID- 8857584
TI  - A role for Rho in receptor- and G protein-stimulated phospholipase C. Reduction
      in phosphatidylinositol 4,5-bisphosphate by Clostridium difficile toxin B.
AB  - Receptors coupled to heterotrimeric guanine nucleotide-binding proteins (G
      proteins) activate phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
      hydrolyzing phospholipase C (PLC) enzymes by activated alpha of free beta gamma
      subunits of the relevant G proteins. To study whether low molecular weight G
      proteins of the Rho family are involved in receptor signaling to PLC, we examined
      the effect of Clostridium difficile toxin B, which glucosylates and thereby
      inactivates Rho proteins, on the regulation of PLC activity in human embryonic
      kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor
      (mAChR) subtype. Toxin B treatment of HEK cells did not affect basal PLC
      activity, but potently and efficiently inhibited mAChR-stimulated inositol
      phosphate formation. PLC activation by the endogenously expressed thrombin
      receptor and by the direct G protein activators, A1F-4 and guanosine 5'-[gamma
      thio]triphosphate (GTP gamma S), studied in intact and permeabilized cells,
      respectively, were also inhibited by toxin B treatment. C3 exoenzyme, which ADP
      ribosylates Rho proteins, mimicked the inhibitory effect of toxin B on GTP gamma
      S-stimulated PLC activity. Finally both toxin B and C3 exoenzyme significantly
      reduced, by 40 to 50%, the total level of PtdIns(4,5)P2 in HEK cells, without
      affecting the levels of phosphatidylinositol and phosphatidylinositol 4
      phosphate. Accordingly, When PLC activity was measured with exogenous
      PtdIns(4,5)P2 as enzyme substrate, Ca(2+)- as well as GTP gamma S- or A1F-4
      stimulated PLC activities were not altered by prior toxin B treatment. In
      conclusion, evidence is provided that toxin B and C3 exoenzyme, apparently by
      inactivating Rho proteins, inhibit G protein-coupled receptor signalling to PLC,
      most likely by reducing the cellular substrate supply.

PMID- 8857585
TI  - The phosphatase inhibitor okadaic acid blocks KCl-depolarization-induced rise of
      cytosolic calcium of rat insulinoma cells (RINm5F).
AB  - It has been shown that okadaic acid (OA) diminishes insulin secretion of rat
      pancreatic islets in response to glucose, glyceraldehyde and KCl. Glucose,
      glyceraldehyde and KCl cause release of insulin by depolarization and subsequent
      opening of L-type calcium channels. Calcium entry into cells is thought to be
      related to protein phosphorylation. To evaluate whether or not OA mediated
      inhibition of insulin secretion in response to depolarization might be due to an
      interference with calcium uptake, we studied its effect on KCl (30 mM)-induced
      increases of cytosolic calcium and discharge of insulin in the insulin secreting
      clonal tumor cell line RINm5F. OA inhibited KCl-stimulated insulin release in
      concentrations > or = 1 microM. In intact RINm5F cells similar concentrations of
      OA decreased the activity of protein phosphates PP-1/PP-2A and inhibited the
      depolarization-induced rise of cytosolic calcium ([Ca2+]i). The latter action
      could also be achieved with the protein phosphatase inhibitor calyculin A,
      whereas the OA analogue 1-nor-okadaone, which is without effect on phosphatases,
      did not affect [Ca2+]i or insulin release. It is concluded that depression of
      depolarization-induced insulin secretion by OA is due to inhibition of calcium
      entry along voltage dependent calcium channels. The data also suggest that in
      RINm5F cells protein phosphatases PP-1/PP-2A are related to the function of
      voltage-dependent calcium channels.

PMID- 8857586
TI  - Dose-dependent effects of berberine on cell cycle pause and apoptosis in Balb/c
      3T3 cells.
AB  - In determining the morphological appearance of Balb/c 3T3 cells from berberine
      treated (100 and 200 micrograms/ml) cultures by light microscopy demonstrated
      that the high berberine concentration (200 micrograms/ml) treatment was
      associated with the accumulation of numerous apoptotic cells, as identified by
      condensed nuclei and decrease in cell size. On the other hand, accumulation of
      cells in G2/M phase instead of induction of apoptosis was observed after 48-72 h
      of 100 micrograms/ml berberine treatment. Berberine was found mainly in cytoplasm
      during berberine-induced (100 micrograms/ml) cell cycle G2/M arrest, while it was
      highly concentrated in nuclei in the induction of apoptosis under high dose of
      berberine (200 micrograms/ml) treatment. Further addition of berberine (100-200
      micrograms/ml) had little effect on the induction of apoptosis in the cells that
      had already been exposed to 100 micrograms/ml of berberine for 48 h. Our results
      suggest that there may exist in Balb/c 3T3 cells an important threshold for
      regulation of cell cycle pause and induction of apoptosis, that is dose
      dependent.

PMID- 8857587
TI  - Exposure to the n-3 polyunsaturated fatty acid docosahexaenoic acid impairs alpha
      1-adrenoceptor-mediated contractile responses and inositol phosphate formation in
      rat cardiomyocytes.
AB  - The beneficial effects of n-3 polyunsaturated fatty acids of fish oil in the
      prevention of fatal arrhythmias in myocardial ischemia were suggested to be at
      least in part mediated by a modulation of dihydropyridine-sensitive L-type
      calcium channels. As cardiac alpha 1-adrenoceptor stimulation has been suggested
      to have no significant effect on L-type calcium channels, the aim of this study
      using cultured neonatal rat cardiomyocytes was to investigate whether chronic n-3
      polyunsaturated fatty acid exposure may have an influence on alpha 1-adrenoceptor
      induced positive inotropic effects and induction of arrhythmias. Pretreatment of
      the rat cardiomyocytes for 3 days in the presence of the n-3 polyunsaturated fish
      oil-derived fatty acid docosahexaenoic acid (60 mumol/l) markedly decreased alpha
      1-adrenoceptor-stimulated increase in contraction velocity and induction of
      arrhythmias. The increase in contraction velocity of the cardiomyocytes induced
      by the beta-adrenoceptor agonist isoprenaline was also markedly reduced by the n
      3 fatty acid pretreatment. Basal contractile amplitude and spontaneous beating
      frequency of the cardiomyocytes were not significantly altered by the
      docosahexaenoic acid exposure. The pretreatment of the rat cardiomyocytes for 3
      days in the presence of docosahexaenoic acid (60 mumol/l) decreased alpha 1
      adrenoceptor-stimulated formation of the calcium-mobilizing second messenger IP3
      and its metabolites IP2 and IP1 by 55%. The depression of IP3 formation by
      docosahexaenoic acid treatment was not mediated by a decreased uptake of myo
      inositol into the cardiomyocytes nor by a decreased synthesis of
      phosphatidylinositol bisphosphate (PIP2), the substrate of phospholipase C. The
      level of glycerol-3-phosphate, an important substrate of the phosphoinositide
      cycle, was unaltered by the docosahexaenoic acid pretreatment. Receptor binding
      studies revealed that the dissociation constant and maximal binding capacity of
      the alpha 1-adrenoceptor antagonist (3H)prazosin was unchanged by the n-3
      polyunsaturated fatty acid exposure. Beta-Adrenoceptor-and forskolin-stimulated
      adenylyl cyclase activities were not diminished by the docosahexaenoic acid
      pretreatment. Chronic exposure of the cardiomyocytes to the n-6 polyunsaturated
      fatty acid arachidonic acid (60 mumol/l) did neither significantly alter alpha 1
      adrenoceptor-induced inositol phosphate formation nor alpha 1-adrenoceptor
      stimulated increase in contraction velocity. The results presented show that
      chronic n-3 polyunsaturated fatty acid pretreatment of rat cardiomyocytes leads
      to a marked impairment of alpha 1-adrenoceptor-induced positive inotropic effects
      and induction of arrhythmias concomitant with a n-3 fatty acid-induced decrease
      in IP3 formation. This derangement of the phosphoinositide pathway by chronic n-3
      fatty acid exposure may, thus, contribute to the beneficial effects of fish oil
      derived fatty acids in the prevention of fatal arrhythmias in myocardial
      ischemia.

PMID- 8857588
TI  - Effects of a myosin light chain kinase inhibitor, wortmannin, on cytoplasmic Ca2+
      levels, myosin light chain phosphorylation and force in vascular smooth muscle.
AB  - Biochemical studies have shown that wortmannin is an inhibitor of myosin light
      chain (MLC) kinase (Nakanishi et al. (1992) J. Biol. Chem. 267: 2157-2163). To
      investigate the role of MLC kinase in smooth muscle contractions, we examined the
      effects of wortmannin on isolated smooth muscles of the rat aorta. Wortmannin (1
      microM) decreased MLC phosphorylation and the amplitude of contractions induced
      by high K+ (72.7 mM) to a level seen at rest. This occurred without a change in
      cytosolic Ca2+ levels ([Ca2+]i). In contrast, wortmannin only partially inhibited
      the sustained contractions induced by phenylephrine (1 microM) and prostaglandin
      F2 alpha (PGF2 alpha, 10 microM) without a change in the [Ca2+]i. On the other
      hand, wortmannin (1 or 10 microM) reduced the increase in MLC phosphorylation
      induced by phenylephrine and PGF2 alpha to a level seen at rest. In the absence
      of external Ca2+, caffeine (20 mM) induced a transient increase in [Ca2+]i and
      force with an increase in MLC phosphorylation. Wortmannin completely inhibited
      the increase in MLC phosphorylation and contraction induced by caffeine without
      affecting the increase in [Ca2+]i. In the absence of external Ca2+, phenylephrine
      induced a small transient increase in [Ca2+]i, MLC phosphorylation and generation
      of force. This was followed by a small sustained contraction without an increase
      in [Ca2+]i and MLC phosphorylation. Wortmannin (1 microM) inhibited the transient
      phase of the contraction and the increase in MLC phosphorylation without
      affecting the transient increase in [Ca2+]i nor the sustained contraction.
      Wortmannin inhibited the Ca2(+)-induced contraction in permeabilized rat
      mesenteric artery, although it did not inhibit the Ca(2+)-independent, ATP
      induced contraction in the thiophosphorylated muscle. These results suggest that
      wortmannin inhibits MLC phosphorylation due to an increase in the entry of Ca2+
      or through the release of Ca2+ from the sarcoplasmic reticulum. The results also
      suggest that the activation of receptors by norepinephrine and PGF2 alpha induces
      a contraction via a MLC phosphorylation-independent pathway or through a pathway
      which is dependent on the resting level of MLC phosphorylation. We conclude that
      wortmannin is a useful tool in studies of the physiological role of MLC kinase.

PMID- 8857589
TI  - Muscarinic acetylcholine receptor trafficking in streptolysin O-permeabilized
      MDCK cells.
AB  - We investigated the validity of streptolysin O (SLO)-permeabilized Madin-Darbin
      canine kidney (MDCK) cells which express muscarinic acetylcholine receptors
      (mAChRs) coupled to pertussis toxin-sensitive guanine nucleotide-binding proteins
      (G proteins) for the study of the molecular machinery that regulated mAChR
      internalization and recycling. Exposure of SLO-permeabilized cells to carbachol
      reduced cell surface receptor number by up to 40% without changing total receptor
      number. The kinetics and maximal extent of receptor internalization as well as
      the potency of carbachol to induce receptor internalization were almost identical
      in SLO-permeabilized and non-permeabilized cells. Using this semi-intact cell
      system, we studied the effect of various agents affecting components potentially
      involved in receptor trafficking. Internalization was prevented by treatment of
      the SLO-permeabilized MDCK cells with (i) the stable ATP analogues, adenosine 5'
      O-(3-thiotriphosphate) and adenylylimidodiphosphate, to block ATP-dependent
      processes, and (ii) heparin to block G protein-coupled receptor kinases.
      Inclusion of the stable GTP analogue, guanosine 5'-O-(3-thiotriphosphate),
      increased the rate but not the extent of receptor internalization. None of the
      membrane-impermeant agents affected receptor internalization in intact MDCK
      cells. This model system also allowed recycling of internalized receptors back to
      the plasma membrane. After removal of the agonist, cell surface receptor number
      in SLO-permeabilized cells returned to control values within 90 min with the same
      kinetics as seen in intact cells. Inclusion of guanosine 5'O-(3-thiotriphosphate)
      shortened the recovery time. These data suggest that both ATP-dependent kinases
      including G protein-coupled receptor kinases and G proteins participate in
      receptor internalization and recycling. In summary, the SLO-permeabilized MDCK
      cell is a feasible model system for the study of mAChR internalization and
      recycling and allows manipulation of the intracellular milieu with membrane
      impermeable macromolecules.

PMID- 8857590
TI  - Promotion of cell growth by stimulation of cloned human 5-HT1D receptor sites in
      transfected C6-glial cells is highly sensitive to intrinsic activity at 5-HT1D
      receptors.
AB  - 5-Hydroxytryptamine (serotonin, 5-HT), essentially known as a neurotransmitter
      and vasoactive agent, also functions as a mitogen in various cell types through
      several different second messenger systems. Stimulation of cloned human 5-HT1D
      receptor sites by sumatriptan in stably transfected rat C6-glial/5-HT1D cells
      promotes cell growth (Pauwels et al. (1996) Naunyn-Schmiedeberg's Arch Pharmacol
      353:144-156). In the present study, the pharmacology of this growth response was
      investigated using a broad series of 5-HT receptor ligands. The data were
      compared with the responses obtained by measuring inhibition of forskolin
      stimulated cAMP formation. 5-HT (EC50: 25 nM) promoted cell growth of C6
      glial/5HT1D cells, and this in contrast to the absence of any measurable effect
      in pcDNA3-plasmid transfected and non-transfected C6-glial cells. The 5-HT effect
      could be mimicked by the following compounds (EC50 in nM): zolmitriptan (0.41),
      2'-methyl-4'-(-methyl[1,2,4] oxadiazol-3-yl)biphenyl-4-carboxylic acid [4-methoxy
      3-(4-methylpiperazin-1-yl)phenyl]amid (GR 127,935;0.86), naratriptan (0.92),
      metergoline (1.9), sumatriptan (2.9), (N,N-dimethyl-2-[5-(1,2,4-triazol-1
      ylmethyl)-1H-indol-3-yl] ethylamine (MK-462; 3.0), and R(+)-8-(hydroxy-2-(di-n
      propylamino)tetralin (R(+)-8-OH-DPAT; 30.7). These EC50 -values correspond to the
      compounds binding affinities at the human 5-HT1D receptor site and, with the
      exception of GR 127,935 and metergoline also to the EC50-values found by
      measuring over 5 min inhibition of forskolin (100 microM)-stimulated cAMP
      formation. Prolonged exposure of GR 127,935(3 h) and metergoline (30 min) to
      cells yielded EC50 values in the cAMP assay more close to those measured in the
      mitogenic response. The growth response to sumatriptan, 5-HT, GR 127,935 and
      metergoline was blocked by the apparently silent antagonist methiothepin,
      ritanserin and ketanserin with potencies similar to blockade of inhibition of
      stimulated cAMP formation. The 8-OH-DPAT effect also is likely mediated by 5-HT1D
      receptors; stereoselectivity was found with its enantiomers at this receptor site
      and the effect was blocked by ketanserin (1 microM) but not by spiperone (1
      microM). Micromolar concentrations of the 5-HT1B receptor agonist 3-(1,2,5,6
      tetrahydro)-4-pyridil-5-pyrrolo[3,2-b]pyril-5-one (CP 93,129) and of the 5-HT2
      receptor agonist 1-(2,5-dimethoxy-4-iodophenyl_-2-aminopropane (DOI) induced cell
      growth with a potency that accorded with the affinity of these compounds for the
      human 5-HT1D receptor site. These effects were sensitive to ketanserin (1 microM)
      antagonism, but not to blockade by beta-adrenergic blockers and the 5-HT2
      receptor antagonist 2-anilino-N-[2-(3-chlorophenoxy)-propyl] acetamidine
      hydroiodide (BW 501-C-67). The findings suggest that 5-HT1A, 5-HT1B and 5-HT2
      receptors are not implicated in 5-HT-stimulated C6-glial/5-HT1D cell growth. In
      conclusion, human 5-HT1D receptors are involved in the growth of C6-glial/5-HT1D
      cells. This cellular response is highly sensitive to the intrinsic activity of
      compounds at 5-HT1D receptors.

PMID- 8857591
TI  - Comparison of 5-HT4 receptors in guinea-pig colon and rat oesophagus: effects of
      novel agonists and antagonists.
AB  - 5-HT4 receptors in isolated distal colon myenteric plexus of guinea-pig,
      mediating contraction of longitudinal smooth muscle, have been further
      characterized by selective agonists and antagonists. The indole agonists, 5-HT
      and 5-methoxytryptamine (5-MeOT), were full agonists (relative to 5-HT) with
      potency values (pEC50) of 8.0 +/- 0.1 (n = 50) and 7.8 +/- 0.1 (n = 12),
      respectively. 5-HT4 receptor agonists of other structural classes, including
      benzimidazolones (BIMU 1 and BIMU 8), and benzamides ((S)-zacopride, (R)
      zacopride, renzapride, SC 49518) were partial agonists with intrinsic activities
      less than that of 5-HT. In general, the potencies for these compounds at 5-HT4
      receptors in guinea-pig colon were similar to the potencies seen in the rat
      isolated oesophagus, where 5-HT4 receptors mediate relaxation. GR 113808 ?[1-[2
      [(methylsulfonyl)amino]ethyl]-4-piperidinyl] methyl1-methyl-1H-indole-3
      carboxylate?, RS 39604 ?1-[4-amino-5-chloro-2-(3, 5-dimethoxybenzyloxy)phenyl]
      3[1-[2-[(methylsulfonyl)amino] ethyl]-4-piperidinyl]-1-propanone hydrochloride
      and SB 204070 ?(1-n-butyl-4-piperidinyl)methyl 8-amino-7-chloro-1, 4-benzodioxane
      5-carboxylate? antagonized 5-HT responses with pA2 values of 9.1 +/- 0.1, 9.0 +/-
      0.2 and 11.0 +/- 0.1, respectively. These affinity values were similar to those
      obtained at 5-HT4 receptors in isolated rat oesophagus (9.0+/- 0.4, 9.3 +/- 0.1
      and 10.6 +/- 0.1 respectively). Despite these operational similarities between 5
      HT4 receptors in guinea-pig colon and rat oesophagus, several novel compounds
      have revealed important differences between 5-HT4 receptors in the two tissues.
      For example, the substituted benzoate, RS 23597 ?3-(piperidine-1-yl) propyl-4
      amino-5-chloro-2-methoxybenzoate hydrochloride, acted as a partial agonist
      (intrinsic activity 0.5) in guinea-pig colon with a potency of 7.6 +/-0.1 (n =
      16). In isolated rat oesophagus, however, this compound was a surmountable
      antagonist (pA2 = 7.8 +/- 0.1) with no intrinsic activity. In contrast, the
      substituted naphthalimide (S)RS 56532 ?(S)-6-amino-5-chloro-2-(1-azabicyclo[2, 2,
      2]octan-3-yl) 2,3-dihydro-1H-benz[de] isoquinoline-1,3-dione hydrochloride?, was
      a potent (pEC50 = 7.9 +/- 0.1), efficacious partial agonist (intrinsic activity =
      0.8) in the rat oesophagus. However, in guinea-pig colon, it was a surmountable
      antagonist with an affinity (pKB) of 9.4 +/- 0.1. Furthermore, several novel,
      selective, 5-HT4 compounds also showed opposing patterns of intrinsic activities
      similar to those described for RS 23597 and (S)RS 56532. It is concluded that
      these differences are inconsistent with differences in 5-HT4 receptor reserves,
      and may suggest that 5-HT4 receptors in the guinea-pig colon and the rat
      oesophagus can be operationally distinguished.

PMID- 8857592
TI  - A microdialysis study of glycinamide, glycine and other amino acid
      neurotransmitters in rat frontal cortex and hippocampus after the administration
      of milacemide, a glycine pro-drug.
AB  - Milacemide is a glycinamide derivative which readily enters the brain and is
      metabolised to glycine. As its mechanism of action as an anticonvulsant drug is
      unknown we used the technique of microdialysis to study the temporal inter
      relationship of glycinamide, glycine and other amino acid neurotransmitters in
      the extracellular fluid of rat hippocampus and frontal cortex. After milacemide
      administration (400 or 800 mg/kg i.p.), glycinamide concentrations rose linearly
      and dose-dependently in both hippocampus and frontal cortex. In contrast, whilst
      glycine concentrations rose in the hippocampus, glycine was unaffected in the
      frontal cortex. Concomitant increases in taurine hippocampal concentrations were
      observed. An increase in serine and a decrease in alanine concentrations was only
      observed at the highest milacemide dose (800 mg/kg). Other amino acids were
      affected. Thus, while glycinamide appears to be universally distributed
      throughout the brain, its metabolism to glycine and its effects on brain amino
      acids appear to be region specific.

PMID- 8857593
TI  - Effect of carbamazepine, oxcarbazepine and lamotrigine on the increase in
      extracellular glutamate elicited by veratridine in rat cortex and striatum.
AB  - Lamotrigine, carbamazepine and oxcarbazepine inhibit veratrine-induced
      neurotransmitter release from rat brain slices in concentrations corresponding to
      those reached in plasma or brain in experimental animals or humans after
      anticonvulsant doses, presumably due to their sodium channel blocking properties.
      Microdialysis measurements of extracellular glutamate and aspartate were carried
      out in conscious rats in order to investigate whether corresponding effects occur
      in vivo Veratridine (10 microM) was applied via the perfusion medium to the
      cortex and the corpus striatum in the presence of the glutamate uptake inhibitor
      L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM in perfusion medium). Maximally
      effective anticonvulsant doses of carbamazepine (30 mg/kg), oxcarbazepine (60
      mg/kg) and lamotrigine (15 mg/kg) were given orally. The uptake inhibitor
      increased extracellular glutamate and aspartate about 2-fold in striatum and
      about 7-fold and 3-fold, respectively, in cortex. Veratridine caused a further 2
      3-fold increase in extracellular glutamate in striatum and cortex, respectively,
      but its effect on extracellular aspartate was less marked in both areas. None of
      the anticonvulsant compounds affected the veratridine-induced increases in
      extracellular glutamate or aspartate in the striatum which were, however,
      markedly inhibited by tetrodotoxin (1 microM) and thus are sensitive to sodium
      channel blockade. In the cortex the same drugs at the same doses did cause about
      50% inhibition of the veratridine-induced increase in extracellular glutamate.
      Carbamazepine and to a lesser extent lamotrigine, but not oxcarbazepine, also
      inhibited the veratridine-induced increase in extracellular aspartate in the
      cortex. Although our results might seem to support the view that inhibition of
      glutamate and aspartate release is responsible for the anticonvulsant effects of
      lamotrigine, carbamazepine and oxcarbazepine, two complementary findings argue
      against this interpretation. First, as previously shown, inhibition of
      electrically induced released of glutamate requires 5 to 7 times higher
      concentrations of these compounds than release elicited by veratrine. Second, the
      present study indicates that doses totally suppressing convulsions caused no
      inhibition in the striatum and at best a 50% inhibition in the brain cortex. From
      this we conclude that the doses used here, although to some extent effective
      against veratridine, did not suppress the release of GLU and ASP elicited by the
      normal ongoing electrical activity of the glutamatergic and aspartatergic neurons
      and that the mechanism of the suppression of convulsions must be sought
      elsewhere.

PMID- 8857594
TI  - Anticonvulsant effect of felbamate in the pentylenetetrazole kindling model of
      epilepsy in the rat.
AB  - The present study was designed to examine the ability of felbamate, a novel
      antiepileptic agent, to antagonize the increase in seizure severity (i.e.,
      chemical kindling) produced by chronic treatment with initially subconvulsant
      doses of pentylenetetrazol (PTZ). Rats were treated with PTZ (30 mg/kg, i.p.,
      three times a week) for 8 consecutive weeks. Two other groups of rats received
      felbamate (300 or 400 mg/kg, i.p.), 90 min before each dose of PTZ. Pretreatment
      with felbamate at either dose prevented the progression of rank of seizures
      during chronic treatment with PTZ. Thus, the mean seizure score by the end of the
      chronic treatment (0-5 scale) was 0 in vehicle treated controls, 3.3 in rats
      treated with PTZ alone, 1.5 in rats treated with PTZ plus felbamate (300 mg/kg,
      i.p.) and 0.9 in the group treated with PTZ plus felbamate (400 mg/kg, i.p.).
      Felbamate also antagonized the long-term increase in the sensitivity to the
      convulsant effects of GABA function inhibitors observed in PTZ-kindled rats.
      Thus, the administration of a challenge dose of isoniazid (120 mg/kg, s.c.),
      picrotoxin (1.5 mg/kg, i.p.) or PTZ itself (15 mg/kg, i.p.), 15 to 45 days after
      the end of the chronic treatment regimen, induced convulsions in > 80% of PTZ
      kindled rats and in < 20% of rats treated with PTZ + felbamate (400 mg/kg). The
      results are discussed in terms of the multiple mechanisms that can contribute to
      the anticonvulsant action of felbamate in the PTZ kindling model of epilepsy.

PMID- 8857595
TI  - The adenosine receptor antagonist theophylline induces a monoamine-dependent
      increase of the anticataleptic effects of NMDA receptor antagonists.
AB  - Previous work revealed that adenosine antagonists as theophylline reversed
      neuroleptic-induced catalepsy and potentiated anticataleptic effects of dopamine
      agonists reflecting specific adenosine-dopamine receptor interactions in the
      central nervous system. We tested whether similar functional interactions exist
      between adenosine receptors and glutamate receptors of the N-methyl-D-asparte
      (NMDA) subtype. The present study demonstrates that the anticataleptic effects of
      the competitive NMDA receptor antagonist CGP37849 and the non-competitive NMDA
      receptor antagonist dizocilpine can be potentiated by coadministration of a
      threshold dose of the adenosine receptor antagonist theophylline (2.5 mg/kg,
      i.p.) in haloperidol (0.5 mg/kg, i.p.)-pretreated rats. This potentiation was
      elicited only with higher doses of CGP37849 (4 and 8 mg/kg, i.p.) or dizocilpine
      (0.16 mg/kg, i.p.) in haloperidol (0.5 mg/kg, i.p.), but not in reserpine (5
      mg/kg, i.p.) plus alpha-methyl-p-tyrosine (100 mg/kg, i.p.)-pretreated animals.
      Therefore, these synergistic interactions seem to be brought about by indirect
      monoamine-dependent mechanisms rather than direct functional interrelationships
      between NMDA and adenosine A2a receptors.

PMID- 8857596
TI  - Chronic intrathecal morphine treatment does not cause down-regulation of spinal
      adenosine A1 receptors in rats.
AB  - We have shown previously that systemic chronic morphine treatment causes down
      regulation of spinal adenosine A1 receptors in rats. Recently, we have found that
      chronic supraspinal morphine treatment also causes this effect. In the present
      study, we investigated whether chronic spinal morphine treatment has the same
      effect of down-regulation of spinal adenosine A1 receptors. Adult male Sprague
      Dawley rats were rendered tolerant to morphine either by multiple intrathecal
      (i.t.) injections or continuous i.t. infusion by osmotic pump administration for
      2 or 4 days. Spinal A1-adenosine receptor binding activity was measured by using
      the selective A1 adenosine agonist [3H]cyclohexyladenosine. No significant
      decrease in [3H]cyclohexyladenosine binding was found in the spinal cord after 2
      or 4 days of multiple i.t. injections of morphine. There was also no significant
      change in the amount of spinal [3H]cyclohexyladenosine bound after 4 days of
      continuous i.t. infusion of morphine by osmotic pump. From these and our previous
      results, it is concluded that only supraspinal chronic morphine treatment down
      regulates the spinal A1 adenosine receptor and this may play a role in the
      mechanism of supraspinal morphine tolerance but not spinal morphine tolerance.

PMID- 8857597
TI  - Morphine-6-O-beta-D-glucuronide but not morphine-3-O-beta-D-glucuronide binds to
      mu-, delta- and kappa- specific opioid binding sites in cerebral membranes.
AB  - We investigated the nature of interaction of morphine-3-O-beta-D-glucuronide
      (M3G) and morphine-6-O-beta-D-glucuronide (M6G) with opioid binding sites at the
      mu-, delta- and kappa-opioid receptors (mu-OR, delta-OR and kappa-OR) in cerebral
      membranes. Saturation binding experiments revealed a competitive interaction of
      M6G with all three opioid receptors. Inhibition binding experiments at the mu-OR
      employing combinations of morphine and M6G resulted in a rightward shift of the
      IC50 for morphine proportional to the M6G concentration, thus strengthening the
      finding of competitive interaction of M6G at the mu-opioid binding site. Data in
      absence and presence of M6G were included in a three-dimensional model. Compared
      to a model with one binding site a model with two binding sites significantly
      improved the fits. This might indicate that different mu-OR subtypes are
      involved. Hydrolysis of M6G to morphine was investigated and did not occur.
      Therefore the effects of M6G on binding to the mu-OR were due to M6G and not due
      to morphine. In contrast, M3G at the three opioid receptors was found to inhibit
      binding being about 300 times weaker than morphine. This effect was well
      explained by the amount of contaminating morphine (about 0.3%) identified by
      HPLC. We conclude that M6G binds to mu-, delta- and kappa-OR in a competitive
      manner. Some of our results on the mu-OR suggest two binding sites for agonists
      at the mu-OR and that M6G binds to both sites. Our results suggest that the high
      potency of M6G as an analgesic is mediated through opioid receptors. In contrast,
      M3G does not interact with the mu-, delta- or kappa-OR. We therefore doubt that
      any effect of M3G is mediated via opioid receptors.

PMID- 8857598
TI  - A complex interaction between topical verapamil and timolol on intraocular
      pressure in conscious rabbits.
AB  - Calcium channel blockers have complex actions on aqueous humour dynamics that
      seem to depend on the route of drug administration. When applied topically,
      verapamil and nifedipine effectively lower intraocular pressure. However, these
      drugs also produce a slight reduction in aqueous humor outflow through the
      trabecular meshwork whereby they could modify the effect of other drugs on
      intraocular pressure. As calcium channel blockers could be effective in the
      management of ocular hypertension and low-tension glaucoma, the aim of the
      present work was to assess the interaction between verapamil and timolol when
      both drugs are topically applied to the eye of albino rabbits. Intraocular
      pressure was measured with a manual applanation tonometer. The effects of 5-6
      different doses of each drug alone and the effects of five mixtures of both drugs
      at fixed concentration ratios (timolol: verapamil 4:1, 2:1, 1:1, 1:2 and 1:4)
      were evaluated. After measuring baseline intraocular pressure, one 50 microliters
      drop of the different solutions was instilled in the left eye. Measures of the
      intraocular pressure were repeated at intervals of 30 min until the maximal
      effect was reached. Each set of experiments was carried out in a group of 9-11
      rabbits. Dose-response curves were fitted with a nonlinear regression
      microcomputer programme. The median effect plot was constructed as proposed by
      Chou and Talalay (1981, 1983, 1984). In order to analyse the nature of the
      interaction between both drugs, the observed effect was compared with the
      theoretically expected one and the combination indices, that relate the doses of
      verapamil and timolol present in the mixtures with the doses of both drugs
      separately which are equieffective with the combination, were calculated. The
      effects of verapamil and timolol followed the principle of the mass action law
      when administered alone. Nevertheless, no adequate dose-response relationship was
      obtained when the mixtures of both drugs were applied. In general, the observed
      effects were lower than the expected ones. Combination indices also indicate the
      presence of antagonism, except for the lowest concentrations of mixtures where
      verapamil predominates. In this case, combination indices suggest summation of
      effects or synergy. Both drugs seem to decrease intraocular pressure by reducing
      aqueous humor secretion through different mechanisms. However, due to the
      reduction of aqueous humor outflow caused by verapamil, the ocular hypotensive
      effect of timolol may be antagonized when high doses of verapamil are
      administered.

PMID- 8857599
TI  - [3H]MDL 100,907: a novel selective 5-HT2A receptor ligand.
AB  - In studies using standard radioligands, unlabeled MDL 100,907 (R-(+)-alpha-(2,3
      dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidinemethanol) has been
      shown to have a high degree of selectivity for the 5-HT2A receptor. The present
      study was undertaken to investigate the receptor binding characteristics of
      [3H]MDL 100,907 in rat cortical homogenates. [3H]MDL 100,907 was found to reach
      equilibrium at 37 degrees C after 15 min. Saturation experiments indicated
      binding to a single site with a KD of 0.56 nM, Hill slope of 1.15, and a Bmax of
      512 fmol/mg protein. In parallel experiments with the standard 5-HT2A receptor
      radioligand, [3H]ketanserin, with prazosin added to block alpha 1 receptors, a
      similar Hill slope and Bmax was noted but a two-fold higher KD was found. In
      competition binding studies using 0.5 nM [3H]MDL 100,907, some 19 standard
      ligands to various receptors including the 5-HT1A, D2, alpha 1, and sigma
      receptors resulted in estimated KI values that were consistent with [3H]MDL
      100,907 selectively binding to the 5-HT2A receptor. A comparison of the KI values
      for 17 standard 5-HT2A receptor agonists and antagonists displacing [3H]MDL
      100,907 versus [3H]ketanserin resulted in a highly significant linear correlation
      (R2 = 0.96, P < 0.001). Taken together these results suggest that [3H]MDL 100,907
      is binding to the 5-HT2A receptor with a sub-nanomolar affinity without the use
      of secondary blocking agents.

PMID- 8857600
TI  - Distribution of 5-HT4 receptor mRNA in the rat brain.
AB  - We have analyzed the brain distribution of the rat 5-HT4 receptor mRNA. A
      receptor specific probe was used for in situ hybridization of rat brain sections.
      Abundant expression of the 5-HT4 receptor mRNA was observed in the olfactory
      system, striatum, medial habenula and the hippocampal formation, while faint or
      no specific signals could be detected in most other areas of the brain. Several
      brain areas which display strong ligand binding do not contain mRNA, suggesting
      an axonal localization of the 5-HT4 receptor.

PMID- 8857602
TI  - Regulation of the promoter of the human corticotropin-releasing hormone gene in
      transfected human endometrial cells.
AB  - Corticotropin-releasing hormone (CRH) is expressed in several peripheral tissues,
      including normal epithelial cells of the human and rodent uterus. However, the
      biological role of endometrial CRH is known in neither species. As a first step
      to clarify this role, we studied the regulation of CRH promoter in endometrial
      cells. We performed homologous transfection experiments in Ishikawa cells, a
      human endometrial cell line, using a 0.9-kb fragment of the 5'-flanking region of
      the human CRH gene coupled to luciferase. Transfected cells were exposed for 18 h
      to 8-bromo cyclic adenosine monophosphate, forskolin, epidermal growth factor,
      steroids (estradiol, progesterone, and the synthetic glucocorticoid dexamethasone
      and their antagonists), and prostaglandin E2; then the activity of the luciferase
      reporter was determined in the cell lysates. We found that the activity of the 5'
      flanking region of the CRH gene was stimulated by cyclic adenosine monophosphate
      and epidermal growth factor and inhibited in a receptor-mediated, dose-dependent
      fashion by estradiol and dexamethasone. The antiglucocorticoid RU 486 acted as a
      glucocorticoid agonist, suppressing the CRH gene activation, while progesterone
      was devoid of any activity. Prostaglandin E2 stimulated the CRH activation, and
      the prostanoid inhibitor indomethacin suppressed it, most probably by inhibiting
      endogenous prostaglandins. These findings suggest that endometrial CRH gene
      expression may be under the negative control of estrogens and glucocorticoids and
      under the positive control of prostaglandin E2.

PMID- 8857601
TI  - Further studies on the mechanism of action of the endogenous benzodiazepine
      receptor ligand octadecaneuropeptide on gonadotropin-releasing hormone gene
      expression in the rat brain.
AB  - We have recently reported that the intracerebroventricular injection of the
      endogenous benzodiazepine (BZD) receptor ligand octadecaneuropeptide (ODN) (30
      micrograms/kg b.w.) could induce a decrease in gonadotropin-releasing hormone
      (GnRH) mRNA levels in the male rat brain. This inhibitory effect could be
      completely reversed by the concomitant administration of the GABAA antagonist
      picrotoxin. In order to further investigate the mechanism of action of ODN, we
      investigated the effects of intracerebroventricular injection of a smaller dose
      of ODN (3 micrograms/kg b.w.) and the influence of the GABAA receptor agonist
      muscimol and the antagonist to BZD receptors flumazenil on GnRH gene expression.
      Treatment with ODN induced a 40% decrease in mRNA levels, an effect which was
      potentiated by the concomitant administration of muscimol. The administration of
      flumazenil produced a small increase in GnRH mRNA while the inhibitory effect of
      ODN on GnRH mRNA levels was completely prevented by the administration of this
      BZD antagonist. Moreover, the intravenous administration of increasing doses of
      ODN also induced a marked decrease of 33, 32 and 38% for 75, 150 and 300
      micrograms/kg b.w., an effect which was completely abolished by picrotoxin. These
      data clearly indicate that an endogenous neuropeptide can activate the GABAA BZD
      receptor complex to negatively modulate the activity of GnRH neurons. They also
      suggest that this peptide or other endogenous activators of the GABAA BZD
      receptors might exert a tonic inhibitory influence on GnRH gene expression.

PMID- 8857603
TI  - Evidence that brain nitric oxide synthase is the major nitric oxide synthase
      isoform in the hypothalamus of the adult female rat and that nitric oxide
      potently regulates hypothalamic cGMP levels.
AB  - Recent studies suggest that nitric oxide (NO) may function as a neurotransmitter
      in the hypothalamus. In order to provide further evidence supporting this
      contention, we examined: (1) whether the hypothalamus displays significant NO
      synthase (NOS) activity and whether the activity is inhibited by an NOS
      inhibitor, (2) whether the different NOS isoforms [brain (b)-NOS, endothelial (e)
      NOS and macrophage (m)-NOS] are expressed in the various nuclei of the
      hypothalamus of the random cycling adult female rat, (3) whether the NO donor
      molecule, sodium nitroprusside (SNP), regulates the heme-containing enzyme,
      guanylate cyclase in the preoptic area and medial basal hypothalamus of the
      random cycling adult female rat as well as the ovariectomized steroid (estradiol
      17 beta)-treated rat. The results of the study showed that the preoptic area
      (POA) and medial basal hypothalamus (MBH) of the adult female rat displays
      significant NOS activity which can be dose-dependently inhibited by an NOS
      inhibitor. All three NOS isoform mRNA transcripts were present in the
      hypothalamus, with the order of expression being b-NOS > e-NOS > m-NOS.
      Immunohistochemical localization using monoclonal antibodies to the specific NOS
      isoform proteins revealed that b-NOS represented the major form of NOS in the
      hypothalamus based on density and distribution of immunostaining. b-NOS
      immunostaining was especially dense in the organum vasculosum laminae terminalis
      (OVLT), medial preoptic area (MPOA), supraoptic nucleus, and moderately dense in
      the arcuate nucleus/median eminence. The pattern and density of b-NOS staining
      closely mirrored our previously reported pattern of NADPH-diaphorase staining in
      the hypothalamus, and a polyclonal antibody to b-NOS yielded a similar staining
      pattern as that observed for the monoclonal antibody. In contrast to the dense
      staining observed for b-NOS in the hypothalamus, we observed no specific staining
      for m-NOS in the hypothalamus. e-NOS immunostaining, on the other hand, was
      present in the hypothalamus, but to a much lesser extent than b-NOS. Light e-NOS
      staining was observed in the OVLT, MPOA, supraoptic nucleus and arcuate
      nucleus/median eminence. That NO can regulate guanylate cyclase as a potential
      mediator of its effects was demonstrated using SNP which dose-dependently
      elevated cGMP levels in the POA and MBH of random cycling rats and estrogen
      primed ovariectomized rats. The effect of SNP was due to its NO donor ability as
      it was blocked by the NO scavenger molecule, hemoglobin. Interestingly,
      hemoglobin alone caused a 50-60% reduction in basal cGMP levels, suggesting that
      endogenously produced NO regulates basal guanylate cyclase activity. Taken as a
      whole, the present study demonstrates that b-NOS is the major NOS isoform in the
      hypothalamus and it also provides evidence that cGMP may be a mediator of NO
      effects in the female hypothalamus as evidenced by the potent ability of SNP to
      elevate cGMP levels in the POA and MBH.

PMID- 8857604
TI  - GABAA receptor-mediated responses in the ventromedial nucleus of the hypothalamus
      of female and male neonatal rats.
AB  - Perinatal exposure of the developing brain to gonadal steroids during a limited
      critical period induces permanent, organizational differences in neural
      structures between male and female animals. These differences are believed to
      underlie the manifestation of sexually dimorphic behaviors. Gamma-aminobutyric
      acid type A (GABAA) receptors expressed in the ventromedial nucleus (VMN) of the
      hypothalamus appear to be a key component underlying the expression of sexually
      dimorphic, and GABAA-mediated transmission within the VMN is critical for the
      expression of sexual behavior in female, but not male, rats. Here we report that
      analysis of VMN neurons from neonatal rats revealed significant sex-specific
      differences in GABAA receptor channel properties. Specifically, GABAA-mediated
      currents elicited by direct agonist application decayed more rapidly in VMN
      neurons from females than from males. Kinetic differences became more pronounced
      during the first 2 weeks of postnatal development. Analysis of small, spontaneous
      inhibitory postsynaptic currents recorded in intact slices indicated a trend
      towards slower responses in neurons from males than females, but the differences
      in decay kinetics were not significant. Sex-specific differences in GABAA
      receptor kinetics may arise from activation of receptors not receiving synaptic
      contacts in the slice preparation or may become apparent at intact synapses under
      conditions of increased activity and evoked release.

PMID- 8857606
TI  - Participation of opioid and serotoninergic systems in prolactin secretion induced
      by hypothalamic action of estradiol.
AB  - The aim of the present study was to determine the central effect of estradiol
      (E2) on the pattern of secretion of prolactin (PRL) in virgin rats and the
      participation of opioid and serotoninergic systems in the regulation of this
      secretion. Bilateral cannulae containing E2 (group E) or cholesterol (group C)
      were implanted in the arcuate nucleus on the day of estrus (day 0). Blood samples
      were obtained at 09.00, 14.00, or 18.00 h on days 1, 3, 6, or 9. All rats were
      blood sampled once. In group E, the PRL levels at 09.00 h on days 1 and 3 were
      similar to those from group C. However, higher values were obtained at 14.00 and
      18.00 h, thus showing a diurnal rhythm with low levels in the morning and high
      values during the afternoon. No rhythm in PRL secretion was observed on days 6
      and 9 in group E in which serum PRL was similarly increased with respect to group
      C at all times. The progesterone (P) levels paralleled PRL concentration, being
      significantly higher in group E at 18.00 h on day 1, at 14.00 and 18.00 h on day
      3, and at all three times on days 6 and 9; the P measurements were consistent
      with luteotropic actions of PRL. Naloxone (NAL; 2 mg/kg i.p.) was injected at
      17.30 h on days 3, 6, or 17, and 30 min later the animals were blood sampled. p
      Chlorophenylalanine (pCPA; 200 mg/kg s.c.) was administered at 07.00 h on days 2,
      5, or 16, and blood samples were taken 35 h later. Control E rats were injected
      with vehicle and blood 18.00 h on days 3 and 6 was not modified by pretreatment
      with NAL or pCPA. Serum P was significantly reduced after pCPA administration on
      days 3 and 6 and after NAL only on day 6. The increase in PRL at 18.00 h on day
      17 induced by E2 was dramatically enhanced by NAL or pCPA, while these treatments
      did not significantly modify serum P levels. Our results indicate an inhibitory
      influence from both opioid and serotoninergic systems on PRL secretion induced by
      the long-term application of E2 in the arcuate nucleus.

PMID- 8857605
TI  - Estrogen rapidly attenuates a GABAB response in hypothalamic neurons.
AB  - GABA is a predominant neurotransmitter in the hypothalamus and an important
      regulator of hypothalamic function. To elucidate the cellular basis for GABAergic
      action in this region, we used intracellular recordings from identified
      hypothalamic neurons. Ninety-three percent of the mediobasal hypothalamic neurons
      responded to GABAB receptor stimulation, and the presence of bicuculline
      sensitive synaptic potentials indicated a tonic, GABAA receptor-mediated input.
      Stimulation of GABAB receptors hyperpolarized these cells by activating an
      inwardly rectifying potassium conductance. We characterized GABAB responses by
      generating concentration-response curves to the GABAB agonist baclofen. There was
      heterogeneity in the responses to baclofen, with one third of the cells having
      low baclofen potency (EC50 = 5.0 microM). Two thirds of the neurons had a 4-fold
      higher potency (EC50 = 1.2 microM), larger somas and a more lateral distribution.
      Previous work has shown that hypothalamic GABAB and mu-opioid receptors open the
      same K+ channels and that the response to mu-opioid agonists is rapidly
      attenuated by 17 beta-estradiol (E2). In order to test the hypothesis that the
      coupling of GABAB receptors to K+ channels is also altered, baclofen
      concentration-response curves were generated before and after an E2 challenge
      (100 nM, 20 min). Consistent with our hypothesis, the potency of baclofen was
      decreased nearly 4-fold in a subset of the cells that had a high potency response
      to baclofen. Furthermore, decreased baclofen potency only occurred in those cells
      in which E2 also altered the mu-opioid responses. Therefore, our findings suggest
      that a discrete subpopulation of hypothalamic neurons is sensitive to estrogen
      actions to alter inhibitory transmission. We propose that the alteration of GABAB
      and mu-opioid input is consistent with estrogen's rapid inhibition of the
      reproductive axis.

PMID- 8857607
TI  - Immunocytochemical and molecular analysis of the effects of glucocorticoid
      treatment on the hypothalamic-somatotropic axis in the rat.
AB  - Glucocorticoids are potent inhibitors of linear growth and growth hormone (GH)
      secretion when secreted or administered in pharmacological amounts in vivo. The
      mechanisms involved require further clarification although enhanced somatostatin
      tone has been suggested to play a role. In this study, we investigated the
      effects of excess glucocorticoids on pituitary GH, hypothalamic GHRH and
      hypothalamic somatostatin through immunocytochemical (ICC) and mRNA analysis.
      Twelve adult male rats were injected daily with dexamethasone (40 micrograms/day,
      i.p.) or saline for 4 days. ICC studies were performed on brain sections from the
      rostral, middle and caudal regions of the median eminence of the hypothalamus
      using the avidin-biotin-peroxidase method. Messenger RNA analyses were performed
      using sense and antisense riboprobes produced from GH, GHRH and somatostatin
      cDNAs. Immunocytochemical results were generated for the percent area and
      intensity (optical density) of immunostaining in the median eminence.
      Glucocorticoids increased somatostatin immunostaining of the rostral, middle and
      caudal regions of the median eminence while GHRH staining was only reduced in the
      rostral region of the median eminence and unchanged in the other hypothalamic
      regions. GH and somatostatin mRNA levels dramatically increased following
      glucocorticoid treatment concomitantly with a decrease in GHRH mRNA levels. Our
      data suggest that increased somatostatin synthesis and storage and a decrease in
      GHRH mRNA synthesis play a major role in the GH inhibitory effects of
      glucocorticoids.

PMID- 8857608
TI  - Sex differences in androgen responsiveness in the rat brain: regional differences
      in the induction of aromatase activity.
AB  - The transformation of testosterone (T) to estrogens in brain tissue by cytochrome
      P-450 aromatase is required for the expression of sexual behaviors in adult male
      rats. Androgens regulate aromatase activity in the medial preoptic nucleus (MPN),
      as well as in a reciprocally connected group of forebrain nuclei involved in the
      regulation of male sexual behaviors. The levels of aromatase in these nuclei are
      generally greater in males than in females due to sex differences in circulating
      androgen levels. However, the mechanism of enzyme induction also appears to be
      sexually dimorphic. The current experiments were undertaken: (1) to characterize
      and compare the kinetic properties of aromatase in male and female rats and (2)
      to study sex differences in the dose-response relationship between the
      administered doses of T and the induction of aromatase in microdissected brain
      regions. Saturation analysis of aromatase activity in the MPN, bed nucleus of the
      stria terminalis (BNST), periventricular preoptic area (PVPOA), anterior
      hypothalamus (AH), and ventromedial hypothalamic nucleus (VMN) indicates that the
      greater aromatase activity observed in intact males reflects a sex difference in
      the maximal enzyme velocity, and not a sex difference in the apparent affinity of
      enzyme for substrate (Michaelis constant). The dose-response study of aromatase
      induction in the BNST, PVPOA, and VMN indicated a sex difference in aromatase
      activity over a range of circulating T levels varying from 0.3 to 35 ng/ml. No
      sex difference in inducible aromatase activity in AH was observed at any dose of
      T. The results of this study clearly demonstrate a sexually dimorphic effect of
      androgen action in the rat brain. Since T both regulates and is the substrate for
      aromatase in the brain, this sexual dimorphism is potentially an important
      limitation to the action of T in females and may relate to the enhanced
      expression of T-stimulated copulatory behavior in males compared to females.

PMID- 8857609
TI  - Involvement of endogneous nitric oxide in the control of pituitary responsiveness
      to different elicitors of growth hormone release in prepubertal rats.
AB  - Recently, nitric oxide (NO) has emerged as an important modulator of several
      neuroendocrine events. Present studies were designed in order to evaluate the
      involvement of endogenous NO in the control of GH secretion. In a first set of
      experiments, in vivo pituitary responsiveness to the elicitors of GH release, GH
      releasing hormone (GHRH), GH-releasing hexapeptide (GHRP-6) and the agonist of
      excitatory amino acid receptors, N-methyl-D-aspartate (NMDA) was tested in
      prepubertal male rats after blockade of endogenous NO by pretreatment (45 min
      before the tests) with the competitive NO synthase (NOS) inhibitors NW-nitro-L
      arginine methyl ester (NAME) and NW-nitro-L-arginine (NA). In addition,
      simultaneous administration of NAME and GHRH to prepubertal males was performed
      and the effects of NO deprivation on GHRH- and NMDA-stimulated GH release in
      prepubertal female rats were studied. In a second set of experiments, the
      involvement of NO in the modulation of GH secretion was analyzed in vitro. GH
      release by dispersed adenohypophysial cells was evaluated after challenge with
      the NO donors, sodium nitroprusside (SNP) and S-nitrosoacetylpenicillamine
      (SNAP), and cGMP, the classical second messenger for NO actions. In addition, the
      ability of NAME, SNP and cGMP to affect the GHRH-induced GH release in vitro was
      also tested. Our results showed that endogenous NO deprivation significantly
      attenuated in vivo GHRH-, GHRP-6- and NMDA-induced GH secretion in prepubertal
      male rats. However, the releasing ability of GHRH was not abolished by
      simultaneous administration of NAME. In addition, pretreatment with NAME blunted
      GHRH- and NMDA-stimulated GH release in prepubertal females. In vitro, neither
      SNP, SNAP, NAME nor cGMP modified GH secretion by pituitary cells in culture but
      NO deprivation by NAME completely blocked GHRH-induced GH release. In addition,
      cGMP but not SNP slightly enhanced GHRH-stimulated GH secretion. Taken together,
      these data strongly suggest that endogenous NO plays a permissive role in the
      control of stimulated GH release and that endogenous NO is an important factor
      eliciting GH secretion in prepubertal rats.

PMID- 8857610
TI  - Evidence for the presence of receptors for pituitary adenylate cyclase-activating
      polypeptide in the neurohypophysis that are positively coupled to cyclic AMP
      formation and neurohypophyseal hormone secretion.
AB  - This study examines the neural lobe of the pituitary gland for the presence of
      receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) and
      their possible involvement in the regulation of neurosecretion. The presence of
      PACAP receptors of type I was revealed in the neural lobe, as well as in anterior
      and intermediate lobes, by means of RT-PCR amplification using selective
      oligonucleotide pairs of primers. They appeared to be expressed in the tissues as
      a short form together with an isoform of heavier molecular weight. Activation of
      receptors in the presence of PACAP stimulated both formation of cyclic AMP (cAMP)
      and secretion of arginine vasopressin (AVP) in neural lobes, in a dose-related
      fashion, with half-maximum (EC50) values of 1.0 +/- 0.2 x 10(-9) M and 1.4 +/-
      0.3 x 10(-8) M, respectively. Parallel with AVP, PACAP also stimulated oxytocin
      (OXT) output, with an EC50 value of 0.6 +/- 0.1 x 10(-8) M. In an attempt to
      localize receptors on cells (mainly astrocyte-like glials or pituicytes) and/or
      on nerve fibers of the gland, we used cultures of neural lobe cells and explants
      (in which nerve fibers undergo degeneration), as well as isolated nerve endings.
      In both cells and nerve terminals, PACAP enhanced accumulation of cAMP, while it
      triggered AVP secretion from the latter. The stimulatory effect of PACAP on both
      AVP and OXT release was mimicked by dbcAMP and blocked by H89, an inhibitor of
      cAMP-dependent protein kinase. We conclude that in the neural lobe, PACAP
      receptors are localized on both nerve terminals and pituicytes, which participate
      in the modulation of secretion of neurohypophyseal hormones in an interactive way
      and mainly through the cAMP signalling route.

PMID- 8857612
TI  - The bladder is an unreliable witness.

PMID- 8857611
TI  - Electrophysiological characterization of non-NMDA glutamate receptors on cultured
      intermediate lobe cells of the rat pituitary.
AB  - Glutamate is the major excitatory neurotransmitter in the central nervous system,
      yet little is known about its actions on endocrine cells. We have investigated
      the membrane effects of glutamate in cultured neonatal rat pituitary intermediate
      lobe (IL) cells using the whole-cell configuration of the patch-clamp technique.
      In a standard Na(+)-based extracellular solution, glutamate failed to induce a
      detectable membrane current at a holding potential (HP) of -60 mV (n = 40).
      However, when cyclothiazide (50 microM), a benzothiazide that blocks
      desensitization of alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazole-propanoic
      acid (AMPA)-type receptors, was added to the extracellular solution, glutamate
      (0.5-1 mM) induced an inward current at a HP of -60 mV in 65% of the cells tested
      (n = 72). This response was usually small in amplitude (mean amplitude: 28.6 +/-
      37.5 pA, n = 47). The glutamate-induced current reversed polarity close to 0 mV
      and was reversibly blocked when extracellular Na+ was replaced by the impermeant
      cation N-methyl-D-glucamine, suggesting that this current was a nonselective
      cation current. The response to glutamate (1 mM) was reproduced by AMPA (50
      microM), kainate (200 microM), and quisqualate (200 microM). N-Methyl-D-aspartate
      (NMDA, 100 microM) in the presence of 10 microM glycine did not induce any
      membrane current in cells responding to glutamate (n = 8). The non-NMDA receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) reversibly inhibited
      the response to glutamate (0.5 mM) by 85 +/- 14% (n = 7), whereas D(-)-2-amino-5
      phosphonopentanoic acid (20 microM), an antagonist of NMDA receptors, had no
      effect on the glutamate-induced current (n = 3). Moreover, we show that although
      the amplitude of the glutamate currents was small, the latter induced large (30
      mV) membrane depolarizations and triggered the firing of action potentials. Taken
      together, our results indicate that neonatal rat IL cells possess AMPA-type
      glutamate receptors that could possibly underlie a fast excitatory glutamatergic
      synaptic input to these cells.

PMID- 8857613
TI  - Lack of correlation of the American Urological Association Symptom 7 Index with
      urodynamic bladder outlet obstruction.
AB  - The objective of this study is to assess whether subjective information from the
      American Urological Association (AUA) Symptom 7 Index correlates with or predicts
      objective urodynamic parameters of bladder outlet obstruction. Seventy-five men,
      mean age 67 years (range 42-85 years), were referred for evaluation of
      "prostatism." Evaluation consisted of the AUA Symptom 7 Index, noninvasive
      uroflow, post-void residual (PVR) urine measurement, and pressure-flow analysis.
      Men were categorized as "obstructed," "equivocal," or "unobstructed" according to
      pressure-flow nomogram of Abrams and Griffiths. The total AUA 7 score, and all
      individual components, were compared with all invasive urodynamic parameters, and
      to the pressure-flow categories of obstructed, equivocal, or unobstructed. The
      AUA index severity categories (mild 0-7, moderate 8-19, and severe > or = 20)
      were compared to the urodynamic pressure flow categories. Thirty-three men had
      severe symptoms, and 42 had moderate or mild symptoms. Forty men were
      urodynamically obstructed, and 35 men were equivocal or unobstructed. There was
      no correlation of any AUA index parameter (total symptom score, obstructive or
      irritative score component, or any individual question) with any noninvasive
      urodynamic parameter. The sensitivity and specificity of the AUA index for
      urodynamic obstruction was 42.5% and 54.3% respectively. Multivariable logistic
      regression analysis was used to determine whether clinical data easily obtained
      in the office setting (age, PVR, noninvasive maximum and average flow rates)
      could predict urodynamic obstruction when combined with any component of the AUA
      index. Only age was found to be a significant predictor of obstruction status (P
      = 0.026). Subjective information from the AUA Symptom 7 Index does not correlate
      with objective data assessing bladder outlet obstruction. Though the AUA index is
      a valid clinical tool, it should not be used to gauge the presence or severity of
      bladder outlet obstruction.

PMID- 8857614
TI  - Combinations of maximum urinary flow rate and American Urological Association
      symptom index that are more specific for identifying obstructive and non
      obstructive prostatism.
AB  - Uroflowmetry and the American Urological Association symptom index (AUASI) are
      often used clinically to evaluate patients with benign prostatic hyperplasia
      (BPH). Since results from these tests may be used to determine a treatment
      course, including surgical intervention, we investigated if specific combinations
      of uroflowmetry and AUASI parameters could better predict urodynamically
      confirmed prostatic obstruction. Data from 134 men (mean age: 67.8 +/- 8.9 years)
      with prostatism were analyzed. The patients underwent uroflowmetry in the
      standing position after completing the AUASI; the post-void residual volume (PVR)
      was determined. The presence and severity of prostatic obstruction was assessed
      by video urodynamics, which included micturitional urethral pressure profilometry
      (MUPP). Of the 134 total patients, 66 were found to be obstructed by MUPP.
      Correlations of maximum urinary flow rate (Qmax), PVR, and AUASI with the degree
      of obstruction were poor and not substantially improved using combinations of
      these parameters. Threshold values of Qmax and AUASI, when used in combination,
      allowed accurate prediction of obstruction or non-obstruction in a small subset
      of the patient population. Of 14 men with both Qmax < 10 ml/s and AUASI > or =
      20, 13 were obstructed (specificity = 98%). Eight of 9 men with both Qmax > or =
      15 ml/s and AUASI < 10 were non-obstructed. The combined Qmax and AUASI criteria
      categorized only 20% of the patients as obstructed or non-obstructed. Once other
      causes of urinary dysfunction are ruled out, use of these criteria will enable
      the urologist to make an accurate diagnosis of obstruction, select a treatment
      more likely to benefit the patient, and make further diagnostic testing
      unnecessary in this small subset of patients. In a large volume clinical practice
      of adult male voiding dysfunctions, diagnosis of even this small proportion of
      patients using this simple approach can reduce patient care costs.

PMID- 8857615
TI  - Impact of different sized catheters on pressure-flow studies in patients with
      benign prostatic hyperplasia.
AB  - The importance of pressure-flow studies for the diagnostic work-up of patients
      suffering from benign prostatic hyperplasia (BPH) has recently been recognized
      more widely. For these studies, several different types and sizes of catheters
      have been used. According to our experience, the degree of obstruction seems to
      be dependent on the catheter size applied. To evaluate the impact of catheter
      size on urodynamic results, 64 male patients underwent pressure-flow studies; 41
      had the clinical diagnosis BPH; 23 were a nonobstructed control group. The 41 BPH
      patients were randomized into two groups: group BPH 1 (n = 20) had a 5F catheter
      and group BPH 2 (n = 21) had a 10F filling catheter in addition to the 5F
      pressure transmission catheter in the urethra. All patients underwent three
      filling and pressure-flow studies. The filling catheter was removed for the third
      pressure-flow study. Peak flow rates (Qmax; ml/s), the corresponding detrusor
      pressure at maximum uroflow (PdetQmax; cm H2O) and the degree of obstruction,
      rated according to the linear passive urethral resistance relation (linear-PURR),
      were assessed. The removal of the 5F (group BPH 1) or 10F (group BPH 2) filling
      catheter resulted in a 21.1% and 55.7% increase of maximum uroflow rate
      respectively. In parallel, we observed a 9.9% and 18.8% decrease of detrusor
      pressure at maximum flow. The degree of obstruction classified according to
      linear-PURR decreased by 14.6% and 21.1% respectively. Furthermore, it became
      evident that five patients (21.7%) of the unobstructed control group could have
      been wrongly interpreted as being obstructed if measured with the filling (10F)
      and the pressure measurement (5F) catheter in situ. In conclusion, the degree of
      obstruction is dependent on the cross-sectional diameter of the used catheters.
      Consequently, standardization with regard to catheter size is mandatory if data
      from different institutions are to be compared.

PMID- 8857616
TI  - Bladder compliance in neurologically intact women.
AB  - No data currently exist to define normal bladder compliance (C) in women. This
      study was undertaken to establish normative data for C in neurologically intact
      women and to determine if detrusor instability (DI) is associated with changes in
      C. The multichannel urodynamic tracings of 270 patients (195 stable, 75 unstable)
      were reviewed according to a standard written protocol. Vesical and abdominal
      pressures (Pves, Pabd) were measured during retrograde filling after a stable
      baseline was established (< 50 ml) and just prior to cessation of infusion. If a
      detrusor contraction occurred, measurements were taken during a 5-sec window
      preceding onset of contraction. The vesical volume used to calculate C was the
      total bladder volume determined by completely emptying the bladder at the end of
      cystometry. Compliance was calculated by dividing this volume by the change in
      detrusor pressure (Pdet). For the purpose of some analyses, infinite C, i.e., no
      observed rise in Pdet, was arbitrarily assigned a value of 1,000. Overall, 47.6%
      of women had no increase in Pdet with filling to maximum cystometric capacity
      (MCC) and had infinite C. Women with instability were significantly less likely
      to have infinite C than those with stable bladders (32% vs. 53%; P = 0.003). In
      75% of women, C was > 130 ml/cm; in 90%, C was > 60 ml/cm; and in 95%, C was > 40
      ml/cm. There were significant differences between the distribution of stable and
      unstable bladders above and below each of these percentile cutoffs. Only 2 women,
      both of whom had unstable bladders, had C < 20 ml/cm water. Ninety-five percent
      of neurologically intact women have C > 40 ml/cm, and nearly half have no
      increase in Pdet during filling to MCC. Patients with DI have significantly less
      compliant bladders than do those with stable bladders. If C is < 40 ml/cm, a
      woman is 16 times more likely to have DI. Decreased C may suggest the diagnosis
      of DI in patients with urge incontinence whose symptoms are not reproduced in the
      laboratory.

PMID- 8857617
TI  - Restoration of micturition in patients with acontractile and hypocontractile
      detrusor by transurethral electrical bladder stimulation.
AB  - The aim of transurethral electrical bladder stimulation (TEBS) treatment in
      patients with diminished detrusor contractility is to attain complete voiding,
      i.e., micturition without residual urine, which is under volitional control. In
      contrast to other types of electrical bladder stimulation, the physiological
      basis for this kind of treatment is sensitizing of the bladder mechanoreceptor
      afferents. The latency of afferent stimuli in normal conditions indicates that
      myelinated A-delta-fibers are used for neurotransmission from these
      mechanoreceptors. Forty-eight patients with hypocontractile or acontractile
      detrusor underwent intravesical electrical stimulation. All patients had a
      history pointing to neurogenic pathology. Forty patients had an acontractile and
      8 a hypocontractile bladder. Prior to therapy, the mean residual urine volume was
      461 ml. After stimulation, 32 of 48 patients were able to void with a mean
      residual of 57 ml. Detrusor contraction was achieved in 39% and bladder sensation
      was perceived by 75% of patients who failed these conditions before treatment.
      Following therapy, 19 of 35 patients were able to empty their bladder without the
      previously needed catheterization. Side effects were epididymitis in 1 and
      cystitis in 7 patients.

PMID- 8857618
TI  - Standardization of terminology and assessment of functional characteristics of
      intestinal urinary reservoirs.

PMID- 8857619
TI  - Analysis of pressure/flow characteristics in the female rat and their
      pharmacologic modulation.
AB  - A new in vivo urodynamic animal model was developed to analyze the micturition
      characteristics of the rat. This model was used to study the modulating effect of
      pharmacological agents on vesicourethral function, using cystometry and
      uroflowmetry. Pressure-flow studies were done in 25 female rats anesthetized with
      urethane. Filling cystometry was recorded using a physiological rate of bladder
      filling through transvesical infusion. Micturition characterization was done by
      identifying the time course and amount of voided volume. Voided volume was
      measured by a novel application of a mechanotransducer, which provided the data
      to measure flow rate and compute the voided volume-time curve. Flow rate was
      calculated by differentiating the curve produced by the mechanotransducer. Using
      this system, comparative tests of pharmacological stimulus were done using
      anticholinergic stimulation, alpha 1, and a new N-methyl-D aspartate (NMDA)
      receptor antagonist. The effects of the intravenous use of these drugs in the
      lower urinary tract were evaluated at various dose levels. The results showed
      that anticholinergic stimulation produced an increase of bladder capacity and
      decreases of detrusor pressure and maximum flow rate. Although the alpha 1
      blocker decreased detrusor pressure, flow rate did not change significantly. By
      contrast, NMDA receptor antagonism produced a depressant effect on bladder reflex
      contraction, and increased bladder capacity in a dose-dependent way. However,
      maximum flow rate increased at a dose of 10 mg/kg and decreased at 30 mg/kg
      significantly. These results suggest that a decrease in flow resistance through
      the outlet region was due to the effects of NMDA receptor inhibition at lower
      doses. In conclusion, this model enables the evaluation of drugs regarding lower
      urinary tract function and provides in small animals the possibility of
      evaluating the relationships between pressure and flow in various experimental
      models.

PMID- 8857620
TI  - Detrusor internal and external work in relation to passive urethral resistance in
      a canine model of the lower urinary tract.
AB  - This study was conducted to evaluate whether passive urethral resistance,
      detrusor internal work, and detrusor external work are independent measures of
      the voiding process. Passive urethral resistance, detrusor internal work,
      detrusor external work, and detrusor total work of 5 canines were determined
      under nonobstructive and obstructive outlet conditions. All urodynamic analyses
      were performed on a surgically exposed urinary tract. Solid-state pressure
      transducers were used to measure the intravesical and distal urethral pressures,
      while an ultrasonic flow meter was used to obtain a simultaneous measure of
      urinary flow rate. Detrusor contractions were induced using bilateral electrical
      stimulation of the pelvic nerves. Varying degrees of outlet obstruction were
      created using an inflatable sphincter cuff secured around the proximal urethra.
      Urethral resistance, internal work, and total work increased with increasing
      obstruction, while external work decreased with increasing obstruction. Internal
      work was linearly and negatively correlated to external work. At low degrees of
      obstruction, internal and external work changed more rapidly than passive
      urethral resistance per unit change in obstruction. As obstruction was increased,
      the change in work parameters per unit change in obstruction decreased, while the
      change in passive urethral resistance per unit change in obstruction increased.
      Our results indicate that at low degrees of outlet obstruction (cuff volume < 60%
      of isometric cuff volume), detrusor internal and external work are more sensitive
      to changes in obstruction than passive urethral resistance. It therefore appears
      prudent to use these work parameters with a passive urethral resistance relation
      (PURR) when evaluating early BPH and also when monitoring its progression. The
      data also show that a detrusor will acutely respond to a change in outlet
      obstruction by modulating its total work output. The mechanisms responsible for
      this response are presently under investigation.

PMID- 8857621
TI  - Electrical stimulated graciloplasty in the male goat: an animal model for
      urethral pressure measurement.
AB  - The feasibility of dynamic urinary graciloplasty as a treatment for incontinence
      is currently investigated. Therefore an animal model is developed to improve the
      technique of dynamic urinary graciloplasty. This article is a report of the
      urethral pressure measurements in the male goat. This study compares the
      graciloplasty around the bulbous urethra with the graciloplasty around the
      bladderneck. The male goat as an animal model of urethral pressure measurements
      is discussed. Under anaesthesia in ten male goats the penile shaft outside the
      pelvis was dissected. Urethral pressure profilometry was performed. The bulbous
      urethra was dissected and a split sling graciloplasty was performed around the
      bulbous urethra. The contralateral gracilis was used for bladderneck
      graciloplasty. Urethral pressure profilometry was done without and with
      electrical muscle stimulation. The highest native urethral pressure was 136 cm
      water at the pelvic outrance. Without stimulation the bladderneck graciloplasty
      pressure was 97 cm water. The bulbous urethra graciloplasty pressure was 122 cm
      water. These pressures were not significantly different from the pelvic outrance
      pressure. With stimulation the highest bladderneck and bulbous urethra
      graciloplasty pressures were 183 cm water and 294 cm water respectively. The
      stimulated bulbous urethra graciloplasty pressure was significantly higher than
      the highest native urethral pressure. In conclusion, the male goat is a suitable
      animal model for urethral pressure measurement. The highest native urethral
      pressure is located at the pelvic outrance. A non-stimulated graciloplasty acts
      like a sling with regard to generated urethral pressure. With stimulation
      sphincterlike activity of the graciloplasty can be observed. In male goats the
      graciloplasty around the bulbous urethra is superior to the bladderneck
      graciloplasty.

PMID- 8857622
TI  - Properties of Ca2(+)-Mg2+ ATP-ase in rabbit bladder muscle and mucosa: effect of
      urinary outlet obstruction.
AB  - The contractile response of the smooth muscle of the urinary bladder is dependent
      upon both the entrance of extracellular calcium through receptor-operated calcium
      channels and the stimulated release of calcium from the sarcoplasmic reticulum.
      In addition, partial outlet obstruction induces marked alterations in the
      utilization of intracellular calcium. Although calcium ATP-ase provides the
      energy for the translocation of intracellular free calcium into storage sites
      within the sarcoplasmic reticulum, very little is known about the properties of
      this enzyme in bladder muscle and mucosa. As an initial study, divalent ion
      specific ATP-ase activity was measured in extracts of rabbit bladder muscle and
      mucosa from control animals and from rabbits following partial urinary outlet
      obstruction. In both normal bladder muscle and mucosa, magnesium and calcium ions
      were equally effective in activating the enzyme. Seven days following partial
      urinary outlet obstruction, the ATP-ase activity in both bladder muscle and
      mucosa was significantly depressed by over 70%. The degree of the decreased
      enzyme activities observed within the muscularis and mucosa would indicate that
      specific membrane functions supported by divalent-ion-ATP-ase are dysfunctional.
      This hypothesis is supported by marked alterations in the utilization of
      intracellular calcium following partial outlet obstruction and the marked
      dysfunctions in both mucosal permeability and bacterial adherence to mucosa
      observed following partial outlet obstruction.

PMID- 8857623
TI  - Age-related differential susceptibility to calcium channel blocker and low
      calcium medium in rat detrusor muscle: response to field stimulation.
AB  - The influences of aging on the response of urinary bladder detrusor smooth muscle
      in response to neurogenic stimulation (electric field stimulation) were
      investigated in rats aged 3-4 months (young) and 18-20 months (old). In addition,
      age-associated changes in calcium homeostasis were evaluated by comparing the
      basal intracellular free calcium concentration ([Ca2+]i), the change of [Ca2+]i
      in response to field stimulation, the contractile response at different
      extracellular calcium concentrations (Ca2+ = 1.8, 0.6, and 0 mM), and the
      sensitivity to the L-type calcium channel blocker. In both groups, the frequency
      response curve in response to field stimulation (1-32 Hz) was similar. The
      contractile response to field stimulation was biphasic (phasic and tonic). The
      phasic/tonic ratio at different frequencies was similar between the two groups.
      The contractile responses were equally inhibited by atropine (1 microM) and
      preincubation with alpha, beta-methylene ATP (50 microM). Tetrodotoxin (1 microM)
      virtually abolished the responses to field stimulation in both groups. The
      biphasic components showed different sensitivities to diltiazem and low calcium.
      The tonic component was more readily inhibited by diltiazem, whereas the phasic
      component was more sensitive to low calcium medium. In general, the response to
      lower frequency stimulations was more sensitive to both diltiazem and low
      calcium. The aged group was more sensitive to the inhibitory effects of both low
      calcium and diltiazem. In Ca2(+)-free medium, the contractile response to higher
      frequency (e.g., 32 Hz) was temporarily preserved in most of the preparations.
      This response disappeared after repeated stimulation. The magnitude of this
      Ca2(+)-free response to 32 Hz stimulation was significantly lower in the aged
      group than in the young group (18.1 +/- 1.4 vs.29.1 +/- 3.2% of the control
      response in normal Tyrode medium, P < 0.05). The basal [Ca2+]i levels were
      similar in the two groups (young: 131 +/- 12 nM, n = 5; old: 118 +/- 10 nM, n =
      4, P > 0.05). The magnitude and time course of the [Ca2+]i response to field
      stimulation were also similar in the two groups. It is concluded that aging seems
      to have little effect on the neuromuscular activities of rat urinary bladder.
      However, the calcium homeostasis may be altered as evidenced by the increased
      sensitivity to diltiazem and low extracellular calcium.

PMID- 8857624
TI  - Significance of rectal contraction noted on multichannel urodynamics.

PMID- 8857625
TI  - Patients' memories of painful medical treatments: real-time and retrospective
      evaluations of two minimally invasive procedures.
AB  - Patients' memories of painful medical procedures may influence their decisions
      about future treatments, yet memories are imperfect and susceptible to bias. We
      recorded in real-time the intensity of pain experienced by patients undergoing
      colonoscopy (n = 154) and lithotripsy (n = 133). We subsequently examined
      patients' retrospective evaluations of the total pain of the procedure, and
      related these evaluations to the real-time recording obtained during the
      experience. We found that individuals varied substantially in the total amount of
      pain they remembered. Patients' judgments of total pain were strongly correlated
      with the peak intensity of pain (P < 0.005) and with the intensity of pain
      recorded during the last 3 min of the procedure (P < 0.005). Despite substantial
      variation in the duration of the experience, lengthy procedures were not
      remembered as particularly aversive. We suggest that patients' memories of
      painful medical procedures largely reflect the intensity of pain at the worst
      part and at the final part of the experience.

PMID- 8857626
TI  - The effect of ethnicity on prescriptions for patient-controlled analgesia for
      post-operative pain.
AB  - We studied if ethnicity influences patient-controlled analgesia (PCA) for the
      treatment of post-operative pain. Using a retrospective record review, we
      examined data from all patients treated with PCA for post-operative pain from
      January to June 1993. We excluded patients who did not have surgery prior to the
      prescription of PCA or were not prescribed PCA in the immediate post-operative
      period. The sample consisted of 454 subjects. While there were no differences in
      the amount of narcotic self-administered, there were significant differences in
      the amount of narcotic prescribed among Asians, Blacks, Hispanics, and Whites (F-
      7,352, P < 0.01). The ethnic differences in prescribed analgesic persisted after
      controlling for age, gender, pre-operative use of narcotics, pain site, and
      insurance status. Patient's ethnicity has a greater impact on the amount of
      narcotic prescribed by the physician than on the amount of narcotic self
      administered by the patient.

PMID- 8857627
TI  - Inpatient vs. outpatient pain management: results of a randomised controlled
      trial.
AB  - Inpatient and outpatient cognitive behavioural pain management programmes for
      mixed chronic pain patients were compared. Patients were randomly allocated to
      the 4 week inpatient programme or to the 8 half day per week outpatient
      programme, or to a waiting list control group. Staff, teaching materials, and
      setting were the same for the two treatment groups. Patients were assessed pre
      treatment, and at 1 month after discharge, and treated patients also at 6 months
      and 1 year after discharge, by assessors blind to treatment group; assessments
      included physical, functional and psychological measures, and medication use. In
      total, 121 mixed chronic pain patients (mean age 50 years; mean chronicity 8.1
      years) were included in the study, following medical examination to ensure that
      no further medical treatment was appropriate. There was no change in the control
      group; inpatients and outpatients, comparable before treatment, both made
      significant improvements in physical performance and psychological function, and
      reduced medication use. Inpatients made greater gains, and maintained them better
      at 1 year; they also used less health care than outpatients. There were no
      outstanding predictors of improvement other than treatment group.

PMID- 8857628
TI  - Spatial summation of heat pain: a reassessment.
AB  - Heat pain threshold is commonly considered to be an 'absolute' value, which is
      not dependent on the area stimulated. In contrast, suprathreshold heat pain
      sensation has been shown to be highly dependent on the area stimulated, with
      considerable spatial summation demonstrated both within and between dermatomes.
      The present study sought to reevaluate two major issues: (a) Whether nociceptive
      thresholds are, indeed, independent of stimulation area. (b) Whether the spatial
      summation of suprathreshold heat pain sensation is independent of threshold
      changes. Using noxious heat we evaluated nociceptive thresholds and perceived
      pain intensity for contact areas of 0.25, 2.25, 6.25 and 15.36 cm2. Our results
      show that considerable spatial summation of heat pain thresholds is obtained and
      an apparent spatial summation of perceived intensity can also be observed.
      However, these apparent changes in perceived pain intensity can be accounted for
      completely by the changes in noxious heat thresholds. Furthermore, when using a
      stimulus configuration in which stimulation area was increased without changing
      nociceptive threshold, no spatial summation of perceived pain intensity was seen.
      Our results suggest that the spatial summation of perceived heat pain intensity
      can be attributed to reduced heat pain threshold. Furthermore, our findings
      stress the importance of determining pain thresholds in studies examining the
      psychophysics of suprathreshold noxious stimuli.

PMID- 8857629
TI  - A parsimonious set of verbal descriptors of pain sensation derived from the
      McGill Pain Questionnaire.
AB  - In view of some recent disagreements about the vocabulary of pain as suggested in
      the McGill Pain Questionnaire (MPQ), the present study re-examined all MPQ pain
      descriptors with regard to their appropriateness as descriptors of pain
      sensation. A sample of 70 undergraduate students (whose first language was
      English) assigned descriptors to individual sensory subcategories and then rated
      them in terms of implied intensity of pain. Data were evaluated using three
      criteria related to the absolute frequency, relative frequency, and unimodality
      of word assignments to each subcategory. Results revealed that about 40% of the
      supposed MPQ sensory descriptors could not be classified within any of the
      sensory subcategories because of incomprehension, underuse, or ambiguity of
      usage. The majority of the words, however, were classified in the same
      subcategories and given similar intensity ratings as in the MPQ. These words
      constitute a parsimonious subset of MPQ descriptors of pain sensation. Such words
      promise more diagnostic specificity in the assessment of pain. Further research
      could serve to replicate these findings as part of the ongoing refinement of the
      MPQ.

PMID- 8857630
TI  - The P300 in pain evoked potentials.
AB  - Pain evoked potentials (EPs) have been used in the last two decades as means of
      obtaining objective measures of pain, in clinical and experimental setups. The
      possibility that the pain EP wave contains elements of the endogenous P300
      potential rather than being a neurophysiological correlate of pain has been
      raised by a number of authors, but the issue has not been resolved. In this
      study, two experiments were performed to study the effect of nonmodality-specific
      factors on the laser EP: (1) a stimulus attend as opposed to a stimulus-ignore
      condition and (2) counterbalanced oddball and task P300 stimulus presentations.
      The latter was to permit full examination of the separate and combined influences
      of each condition on the EP. Stimuli were given to the radial hand of 10 healthy
      volunteers using a CO2 laser. The positive component of the laser EP was affected
      by both manipulations relating to (1) attention (P = 0.0146) and (2) the
      frequency condition (P = 0.003) in the P300 paradigm. The task condition in the
      second paradigm did not affect the positive wave on its own, although its effect
      was visible in interaction with frequency (P = 0.033). In conclusion, although
      the presence of a somatic component in the laser EP cannot be rules out, we
      suggest that the laser EP contains a definite non-modality-specific P300
      component, and is not a pure neurophysiological correlate of pain intensity.

PMID- 8857631
TI  - The effect of Ketamine on stimulation of primary and secondary hyperalgesic areas
      induced by capsaicin--a double-blind, placebo-controlled, human experimental
      study.
AB  - The non-competitive NMDA-antagonist, Ketamine, was infused (i.v.) in healthy
      volunteers to study the effect on central excitability with the presence of
      cutaneous hyperalgesia. Hyperalgesia was established experimentally on the dorsum
      of the foot by topical application of capsaicin (1%). Different thermal and
      mechanical conditioning stimuli were applied to the primary and secondary
      hyperalgesic areas to modulate the central nociceptive excitability monitored by
      the nociceptive reflex. When the elicited reflex was combined with an activation
      of the secondary hyperalgesic area by continuous, non-painful, electrical
      stimulation, a facilitation of the reflex was observed. This indicates that
      summation of activity in non-nociceptive and nociceptive afferents can occur
      under mild pathological conditions. Conditioning thermal stimuli of the primary
      hyperalgesic area were employed to intensify the allodynia prior to testing this
      interaction between tactile and nociceptive activity. The same reflex
      facilitation was inhibited by Ketamine. Furthermore, Ketamine decreased the pain
      intensity associated with the stimuli eliciting the reflex. Psychophysical
      measures to single and repeated electrical and thermal (laser) stimuli applied
      within the hyperalgesic areas were also obtained. The intensity of pain
      sensations produced by single, painful, electrical stimuli applied to the primary
      hyperalgesic region was reduced after Ketamine infusion. Finally, five repeated,
      electrical stimuli applied to the secondary hyperalgesic area were used to assess
      the temporal summation threshold. Ketamine caused an increase in the summation
      threshold compared to the placebo treatment. In conclusion, these results
      demonstrate that (1) summation of activity in non-nociceptive and nociceptive
      afferents occurs under hyperalgesic conditions and, (2) this summation can be
      inhibited by NMDA-antagonists. Therefore, the study shows an apparent involvement
      of NMDA-receptors in some of the central mechanisms underlying secondary
      hyperalgesia.

PMID- 8857632
TI  - Successful treatment of shoulder pain syndrome due to supraspinatus tendinitis
      with transdermal nitroglycerin. A double blind study.
AB  - We have conducted a prospective double blind randomized and placebo controlled
      clinical study in 20 patients with shoulder pain syndrome caused by supraspinatus
      tendinitis to determine whether transdermal nitroglycerin (NTG) has analgesic
      action in this condition. In a randomized manner we used a 5-mg NTG (Nitroplast)
      patch per day over 3 days or similar placebo patches applied in the most painful
      area. Patients were evaluated before treatment was initiated and after 24 and 48
      h. The assessment was made blindly by the same clinical investigator. The follow
      up showed a significant decrease in intensity of pain at 24 h (7.05 +/- 0.4 to
      4.5 +/- 0.5) and 48 h (2 +/- 0.3) in the NTG group (P < 0.003). No changes were
      observed in the placebo group. The mean pain duration, activity of the extremity
      and hours of sleep also improved in the NTG group, with no significant
      modification in the placebo group. Two patients experienced headache as a side
      effect 24 h after treatment was started. Patients in the NTG group remained free
      of symptoms when they were assessed 15 days later. We conclude that NTG is useful
      in the treatment of shoulder pain syndrome caused by supraspinatus tendinitis and
      that this treatment could be a useful approach to the management of this common
      disturbance and probably also in other tendon musculoskeletal disorders.

PMID- 8857633
TI  - Computer-controlled lidocaine infusion for the evaluation of neuropathic pain
      after peripheral nerve injury.
AB  - BACKGROUND: Systemic lidocaine has been reported to be effective in treating
      several neuropathic pain syndromes. Few reports relate plasma lidocaine
      concentration to analgesia and the available studies have been complicated by
      labile plasma lidocaine concentrations. We used a computer-controlled infusion
      pump (CCIP) to target and maintain stable plasma lidocaine concentrations and
      study the effect of intravenous lidocaine on (1) pain scores, (2) current
      perception thresholds, (3) side effects, and (4) pain distribution in patients
      suffering from peripheral nerve injury pain. METHODS: This study used a
      randomized double-blind placebo-controlled design. Eleven patients suffering from
      neuropathic pain after peripheral nerve injury received both a lidocaine and
      saline infusion in separate study sessions. The order of the study sessions was
      randomized and separated from each other by 1 week. The CCIP was programmed to
      target plasma lidocaine concentrations of 0.5, 1, 1.5, 2, and 2.5 micrograms/ml,
      each held for 10 min. Pain scores and pain distribution were assessed in the
      painful area, and electrical current perception thresholds (CPT) of the ring
      finger were measured using a cutaneous perception threshold neurometer
      (Neurometer CPT, Neurotron, Baltimore, MD). Side effects were recorded at fixed
      intervals. Plasma lidocaine concentrations were measured at 4 and 9 min after
      each step increase in infusion and correlated with the observed effects. RESULTS:
      Saline infusion had no effect. However, with lidocaine there was a significant
      plasma concentration-dependent decrease in pain scores starting at 1.5
      micrograms/ml. This effect typically corresponded with a decrease in the size of
      the receptive field to which the pain was referred. For the electrical stimulus,
      there was no significant effect on cutaneous perception at 2000-Hz stimulation at
      the highest concentration examined; however, there was a significant increase in
      thresholds at 250-Hz (starting at 1.5 micrograms/ml) and 5-Hz (starting at 1.0
      micrograms/ml) stimulation. There were no serious side effects. In all, 54.5% of
      patients reported lightheadedness (average plasma lidocaine concentration: 1.5
      micrograms/ml) and one patient reported nausea (2.3 micrograms/ml). DISCUSSION:
      The computer-controlled delivery of intravenous lidocaine results in relatively
      stable plasma concentrations which allows a more thorough evaluation of the
      relationship between plasma concentration and patient response. This
      administration methodology for intravenous lidocaine may prove to be a valuable
      clinical and research tool.

PMID- 8857634
TI  - CO2 laser activation of nociceptive and non-nociceptive thermal afferents from
      hairy and glabrous skin.
AB  - In 8 healthy subjects we have recorded cerebral evoked potentials and reaction
      time (RT) to CO2 laser stimulation of the hairy and glabrous skin at low and high
      stimulus intensities, corresponding to subjective reporting of detection and
      pain, respectively. At each intensity we were able to identify an evoked
      potential; the latencies of the major vertex positive (VP) components fell into 2
      distinct populations 320 +/- 30 (VP300) and 778 +/- 80 (VP800) which did not
      differ between stimulation sites. The frequency of the VP300 responses was
      greatest in the high stimulus conditions and lower in the low stimulus conditions
      whilst the opposite was true for the VP800 responses. BImodal distributions of RT
      were seen at both stimulus intensities. In a further group of of 10 subjects we
      recorded the latency shift of the vertex negativity following proximal and distal
      stimulation of hairy skin of the left upper limb and derived conduction
      velocities for the VP300 (13.21 +/- 2.8 m/sec) and VP800 (1.26 +/- 0.29 m/sec)
      responses. These results suggest that, following CO2 laser stimulation of both
      hairy and glabrous skin, two different fibre populations are activated. The VP300
      responses appear to be related to A delta activation, while the characteristics
      of the VP800 responses are consistent with activation of thermoreceptors mediated
      by C fibres.

PMID- 8857635
TI  - Sensitisation of visceral afferents by nerve growth factor in the adult rat.
AB  - Since there is growing evidence that nerve growth factor (NGF) acts as a mediator
      of persistent pain states, here we have studied its acute effects on the
      properties of primary afferent neurones innervating adult rat urinary bladder.
      Single A delta and C fibres were dissected from the L6 or S1 dorsal roots of
      urethane anaesthetized rats. The stimulus-response function of these afferents
      was evaluated with a series of isotonic distensions of the bladder (0-60 cm H2O).
      The afferents were then studied after filling the bladder with a vehicle solution
      of 10% DMSO for 30 min, and then again after filling the bladder with a 10
      micrograms/ml solution of human recombinant NGF in 10% DMSO. In the control
      state, and after filling with 10% DMSO, the myelinated and about one-half of the
      unmyelinated afferents were mechanosensitive with pressure thresholds in the
      innocuous range and responsiveness extending into the supra physiological,
      presumed noxious range. The remaining one-half of unmyelinated afferents showed
      no mechanosensitivity. After filling with NGF, the large majority of units, both
      myelinated and unmyelinated, sensitised, evidenced by the development of ongoing
      activity and a leftward shift of stimulus-response functions. Some of the
      initially nonmechanosensitive units developed a novel mechanosensitivity. The
      sensitisation began within 30 min of exposure to NGF, and persisted for the
      period studied (up to the 3 h). In separate experiments, intravesical NGF at
      concentrations greater than 1 microgram/ml was found to elicit a dose-dependent
      extravasation of Evan's blue into the bladder. These data support the notion that
      NGF may be an endogenous mediator in some persistent pain states.

PMID- 8857636
TI  - Stimulus properties and antinociceptive effects of selective bradykinin B1 and B2
      receptor antagonists in rats.
AB  - Research has documented the differential role of bradykinin (BK) B1 and B2
      receptors in the mediation of inflammatory nociception and this research suggests
      that selective B1 antagonists may have therapeutic potential against chronic
      inflammatory pain. The present study sought to further define the stimulus
      properties (reinforcing and aversive effects) of the selective B1 antagonist des
      Arg9,(Leu8)-BK (0.0, 0.03, 0.1, and 0.3 mg/kg) and the selective B2 antagonist
      HOE 140 (0.0, 0.1, 0.5, and 1.0 mumol/kg) in the Freund's adjuvant (100
      microliters, i.p.) model of chronic inflammatory nociception using the place
      preference paradigm. In addition, this research examined the differential
      antinociceptive effects of these antagonists on the formalin test (2.5%). Des
      Arg9,(Leu8)-BK exhibited antinociceptive effects against both the first and
      second phases of the formalin response; HOE 140 tended to increase nociceptive
      responding on both phases of the formalin response. In the place preference
      paradigm, des-Arg9,(Leu8)-BK, but not HOE 140, exhibited negatively reinforcing
      effects (i.e. analgesia) in adjuvant-inflamed animals and aversive effects in
      noninflamed control animals. Neither compound exhibited positively reinforcing
      effects (i.e. abuse potential). These results further define the stimulus
      properties of these selective BK antagonists and provide additional evidence to
      support the notion that B1 antagonists may possess therapeutic potential for
      conditions of chronic inflammatory pain.

PMID- 8857637
TI  - Intracranial ependymomas of childhood. Lack of correlation of histopathology and
      clinical outcome.
AB  - The histopathology of 66 children with the diagnosis of ependymoma who were
      operated on at our institution between 1954 and 1994 were reviewed. We performed
      an initial analysis using the entire study cohort to determine which
      histopathological features associated with each other in a statistically
      significant fashion in an attempt to identify combinations of features that
      together might be useful in predicting outcome. A detailed outcome analysis was
      then performed on the 37 most recent cases who survived the postoperative period,
      in whom pre- and post-imaging studies as well as long term follow-up were
      obtained, in order to identify the histopathological features and combinations of
      features that were predictive of overall and progression-free survival. Five- and
      ten-year progression-free survivals were 45.1% and 36.1%, respectively. Overall
      survivals were 57.1% and 45.0%, respectively. Of the eight individual
      histopathological features, only the presence of necrosis was found to correlate
      with a less favorable overall and progression-free survival (PFS) (p = 0.06 and
      0.03, respectively). In addition, the combination of necrosis with vascular
      proliferation or nuclear pleomorphism was associated with a worse PFS (p = 0.01
      and 0.02, respectively). However, when other clinical predictive factors were
      included in a multivariate regression analysis, none of the histological features
      or combinations of features were independently associated with outcome. In
      addition, no relationship was found between the pattern of rosettes (true
      rosette, pseudorosette, or perivascular pseudorosette) and clinical outcome. In
      conclusion, although this study found an association between certain
      histopathological features and clinical outcome in children with ependymomas,
      these relationships did not reach statistical significance on multivariate
      analysis and, thus, do not provide sufficient evidence for modifying therapy
      based on histopathology alone.

PMID- 8857638
TI  - Molecular analysis of ocular adnexal lymphoid proliferations. Characteristics of
      immunoglobulin VH, D and J segment usage.
AB  - We investigated the molecular characteristics of six cases of ocular adnexal
      lymphoid proliferation. Although their clinical diagnoses varied, all of them
      were diagnosed as having malignant lymphomas by immunohistochemical examinations
      and molecular approaches. Proliferating cells showed the B cell phenotype,
      positive for L26/CD20 and negative for UCHL1/CD45RO, and genotypic study by
      Southern blotting revealed that all cases had gene rearrangements of the
      immunoglobulin heavy chain with or without those of the kappa (kappa) light
      chain. Epstein-Barr virus infection was not identified. Usage of variable domains
      of the immunoglobulin heavy chain was analyzed. Subgroup 3 of the VH gene was
      present relatively often, in 3 of 6 cases, perhaps due to its having the largest
      number of VH gene segments. On the other hand, an unexpectedly high frequency of
      the DLR family of the D gene segment was observed by sequencing the third
      complementarity determining region. These molecular characteristics in ocular
      adnexal lymphoid neoplasms might be related to the clinical course.

PMID- 8857639
TI  - Detection of ras oncogene point mutations and simultaneous proliferative fraction
      estimation in gallbladder cancer.
AB  - Gallbladder cancer is notorious for its poor clinical evolution; so, a study of
      parameters with any prognostic potential is of particular interest. In this
      study, we investigated 23 adenocarcinomas regarding both the presence of point
      mutations in the ras gene family and the quantitative expression of Proliferating
      Cell Nuclear Antigen (PCNA). We respectively used molecular biology techniques
      and immunohistochemistry. Our results were related to several clinicopathologic
      determinators as well as to patients' survival. Mutations in codon 12 of the K
      ras gene were detected in four gallbladder neoplasms (17%). This specific type of
      mutation is likely to be partially involved in this organ's tumourigenesis,
      particularly since no H-ras codon 12 or K-ras codon 13 (aspartic acid) mutations
      were detected in any of our specimens. PCNA immunoreactivity was generally
      limited in all tumours studied except for those morphologically characterized as
      being particularly aggressive. Notably, the four tumours in which K-ras mutation
      was detected, demonstrated relatively high PCNA positive immunoexpression in
      their malignant cells. This finding reinforces a possible correlation between the
      presence of ras mutations and increased cell growth. Staging was the only factor
      which was statistically associated with survival (p < 0.01). Therefore, the poor
      evolution of this cancer is probably due to late diagnosis and not related to a
      model of increased biologic aggressiveness.

PMID- 8857640
TI  - Granular cell ameloblastoma. An immunocytochemical study.
AB  - Granular cell ameloblastoma is characterized by nests of large, eosinophilic
      granular cells. These latter have long been the subject of debate. Two cases of
      granular cell ameloblastomas have been immunocytochemically stained with a panel
      of antibodies against human mitochondria, S-100 protein, CD 68, low molecular
      weight cytokeratins, chromogranin, laminin, vimentin, PCNA, bcl-2 and p-53.
      Granular cells exhibited a membranous positivity with cytokeratins while the non
      granular cells of the same tumors showed a diffuse cytoplasmic reactivity.
      Moreover, granular cells showed marked cytoplasmic positivity with CD68 antiserum
      only while human mitochondria, as well as S-100 protein antisera, were
      consistently negative. PCNA, bcl-2 and p-53 did not stain the granular cells.
      These results allow easy distinction of granular cell ameloblastomas from similar
      tumors exhibiting granular cell changes and indicate that the granularity in
      ameloblastoma cells is consequent to lysosomal overload.

PMID- 8857641
TI  - Localized amyloid in the menisci of the knee joint.
AB  - This is, to the best of our knowledge, the first report on amyloid deposits in
      menisci. Fragments of menisci gained by arthroscopy from 316 patients between 20
      and 80 years of age were examined. Amyloid was found in 70% of the cases from
      male, as well as female patients. The amyloid amount found was always very small,
      but the deposits seemed to increase with age. Patients more than 50 years of age
      all had menisceal amyloid. Two types of deposits were observed: a)stroma-deposits
      in the deep central portions of the menisci (tiny dots of intensely stained
      amyloid and/or ill defined patches of low staining intensity) and b) surface
      associated deposits: band-like amyloid imbibition of the collagenous stroma
      immediately beneath the surface of the menisci but not deeper than 0.2 mm. In all
      cases, amyloid was resistant when pretreated by KMn04 and immunohistologically
      antisera against amyloid types AA, AB and AF were negative. 3/25 cases showed a
      reaction with an amyloid-lambda-antibody. We assume, that amyloid in menisci is a
      further type of localized senile amyloidosis.

PMID- 8857642
TI  - Cytokeratin expression in preneoplastic lesions and early squamous cell carcinoma
      of the bronchi.
AB  - Cytokeratins are expressed in varying combination in the course of
      differentiation of epithelial cells and tumor cells. This is the first report of
      systematic immunohistochemical (ABC-method) investigations concerning the
      expression of different cytokeratin types (KL 1, CK 4, 10 and 17) within the
      transformation of the bronchial mucosal epithelium with epithelial hyperplasia to
      potential preneoplasia and early squamous cell carcinoma of the lung. In
      bioptical obtained specimens from 35 patients, 63 areas with diagnosis of regular
      bronchial mucosa (n = 10), basal cell hyperplasia (n = 9), goblet cell
      hyperplasia (n = 10), squamous cell metaplasia (n = 11), dysplasia I-III (n =
      13), carcinoma in situ in the border zone of squamous cell carcinoma (n = 10) and
      in 5 surgically obtained specimens with findings of an early squamous cell
      carcinoma of the bronchus (n = 5), the expression of different cytokeratin types
      was investigated. The specimens were fixed in formalin and embedded in paraffin
      for lightmicroscopical and immunohistochemical investigations (ABC-method). KL 1
      was detected in all regular and pathological mucosal epithelia, CK 4 in basal
      cells, squamous cell metaplasia, potentially preneoplastic changes and early
      squamous cell carcinoma of the bronchus. CK 10 was expressed only in early
      squamous cell carcinoma of the bronchus, and CK 17 in varying quantity in
      hyperplastic, preneoplastic and cancerous lesions of the bronchial mucosa. Our
      results reveal an increasing expression of squamous epithelial type-cytokeratins
      (CK 4, CK 17) in hyperplastic and metaplastic lesions of the bronchial mucosa. In
      dysplastic lesions and carcinomata in situ, a quantitative, as well as
      qualitative decrease of the CK 4- and CK 17-expression with a heterogeneous
      expression pattern for CK 17 was found. The heterogeneous neo-expression of CK 10
      in early squamous cell carcinoma of the bronchus has to be emphasized.

PMID- 8857643
TI  - Atypical lymphoid infiltrations of the gastric mucosa--their interpretation and
      management by eradication of Helicobacter pylori.
AB  - Low-grade gastric lymphomas of mucosa-associated lymphoid tissue (MALT) may be
      extremely difficult to differentiate from atypical lymphoid infiltrations of the
      gastric mucosa caused by Helicobacter pylori (H. pylori) infection, especially if
      lympho-epithelial destructions are not detected. In order to clarify this
      diagnostic problem and to evaluate the potential benefit of clearing H. pylori
      induced lymphoid infiltration a prospective study was performed. Our study
      included biopsy specimens from 61 patients, that showed excessive lymphoid
      infiltrations. Using histology and immunohistochemistry no definite diagnosis
      could be delivered. In 46 (76.4%) cases histological regression occurred 4 weeks
      after the end of therapy suggesting a reactive infiltrate. In 7 patients (11.5%)
      the histological picture remained unchanged, and in 8 (13.1%) the follow-up
      biopsies revealed lympho-epithelial destructions allowing the diagnosis of low
      grade MALT lymphoma. On the basis of our data we conclude that eradication of H.
      pylori could provide an additional tool in the differential diagnosis between
      atypical lymphoid infiltrations of the gastric mucosa caused by H. pylori and an
      early primary gastric MALT lymphoma.

PMID- 8857644
TI  - 4D confocal microscopy for visualisation of bone remodelling.
AB  - Until recently it was very time consuming and difficult to make three-dimensional
      (3D) images of newly formed bone. With the advent of confocal technologies and
      increased computer power, 3D imaging is greatly facilitated. In this paper we
      demonstrate that enhanced confocal visualisation of newly formed bone is possible
      when bone is labelled in vivo sequentially with two osteotropic markers (xylenol
      orange and tetracycline). Computer-assisted reconstruction of the confocal
      optical sections was achieved through the use of the CONVEX Application
      Visualisation System (AVS). The computerised image data provides the researcher
      with ample flexibility in displaying the results. It was found that CSLM combined
      with AVS is excellent for visualising the remodelling process in three and four
      dimensions, in which the fourth dimension is time. With this approach visualised
      bone remodelling has become possible in a manner not easily achieved by other
      techniques.

PMID- 8857645
TI  - Osteoclast cytomorphometry in patients with femoral neck fracture.
AB  - In patients with femoral neck fracture, nutritional deficiencies have been shown
      to be common. A low calcium diet and/or a reduced vitamin D intake have been
      suspected to cause secondary hyperparathyroidism responsible for increased bone
      turn over and bone loss. Parathyroid hormone (PTH) levels are increased in these
      patients, data which are in accordance with the pronounced changes observed on
      bone biopsies reflecting a true hyperparathyroidism. We have used a
      cytomorphometrical approach to characterize PTH-induced changes on the
      osteoclastic population. Osteoclasts were detected histochemically (by tartrate
      resistant acid phosphatase staining) on bone biopsies from 10 control subjects, 8
      patients with primary hyperparathyroidism and 10 patients with a femoral neck
      fracture of osteoporotic origin. The maximum Feret's diameter of each osteoclast
      (Oc.Le) was determined with a semiautomatic image analyzer. In all groups, the
      frequency distribution of Oc.Le appeared positively skewed. In both hip fractured
      patients and primary hyperparathyroid patients, the mode of the distribution was
      higher (25-30 microns) than in controls (20-25 microns). When graphically
      converted on a probability graph, the osteoclastic populations appeared
      homogeneous and well described by a lognormal distribution in the three groups.
      However, osteoclasts appeared similarly enlarged in the groups of patients with
      primary hyperparathyroidism and with femoral neck fracture. PTH has been shown to
      increase both the recruitment of mononucleated precursors and their fusion into
      larger osteoclasts than controls. In the present study, a cytomorphometric method
      appeared able to identify the border line hyperparathyroidism in the hip
      fractured patients.

PMID- 8857646
TI  - Histopathology of the frozen prostate. The microscopic bases of prostatic
      carcinoma cryoablation.
AB  - In the last few years percutaneous cryoablation surgery of the prostate has been
      re-introduced as an alternative means to treat prostatic carcinoma. Advantages of
      the technique include local effectiveness in eradicating tumors, minimal
      morbidity rate and lower costs when compared to radical surgery. We report a
      study documenting the histopathological changes seen in 317 biopsy specimens
      obtained from 30 patients (age range 59-83 years, median 73 years) treated with
      cryosurgical ablation for prostate cancer. Pre- and postoperatory assessment was
      inclusive of plain clinical, laboratory and instrumental data (digital rectal
      examination, transrectal ultrasound scan, serum prostatic specific antigen
      concentration) and systematic biopsies obtained from conventional and modified
      prostate sextants. Fifteen patients had tumors extending through the prostate
      capsule (pT3 and pT4). Six patients had stage PT1 tumors and 9 had stage pT2.
      Tissues were sampled at 3, 6 and between 12-18 months postoperatively. The
      histologic findings, in decreasing order of frequency, were: full core fibrosis,
      necrosis, granulation tissue, basal cell hyperplasia, cell swelling, hemosiderin
      deposits, chronic inflammation, thick nerves and prostatic hyperplasia. Necrosis
      was of the coagulative type, sometimes associated with nuclear debris, and seen
      at relatively short interval from cryotherapy. Fibrosis with hyaline qualities
      was seen especially at 12-18 month interval. The presence of necrosis, as well as
      granulation tissue, hemosiderin deposits and cell swelling, strongly correlate to
      intervals from cryosurgical ablation. Residual tumor tissue was focal (0.5-1 mm)
      and recognizable in 9 cores from 4 patients (13.3%) sampled especially from the
      prostatic apex. Incipient tumor necrosis was seen in 11 cores, without particular
      distribution. These findings indicate that cryosurgery results in distinctive
      changes in both tumoral and non-tumoral prostate tissue. Knowledge of the
      histopathologic patterns is important since it provides the clinicians with
      information on treatment efficacy or failure, and could assist in the selection
      of larger groups of patients eligible to cryosurgical ablation.

PMID- 8857647
TI  - Microwave pretreatment improves RNA-ISH in various formalin-fixed tissues using a
      uniform protocol.
AB  - RNA is situ hybridization technique (RNA-ISH) is hampered by formalin fixation of
      tissues. This necessitates a pretreatment step of enzymatic digestion. However,
      to achieve the best results, digestion times and concentrations of enzymes have
      to be adapted for every specimen in a cumbersome procedure. Microwave
      pretreatment (MP) of formalin-fixed tissues has developed to become a powerful
      tool in immunohistochemistry (IHC) in recent years. To evaluate whether MP could
      also be helpful for RNA-ISH, we compared MP and conventional enzymatic
      pretreatment systematically using different tissues and various fixation times.
      As a model for RNA-ISH we chose the detection of kappa/lambda light chain mRNA in
      tonsils and lymph nodes with follicular hyperplasia and lymph nodes of patients
      with lymphocyte predominant Hodgkin's Disease (LPHD). Signal intensity obtained
      after MP was at least as good or dramatically enhanced as that obtained with
      optimized, single case adapted conventional pretreatment, the morphology being
      much better preserved after MP. These results confirm MP as a suitable method to
      unify the staining protocols in RNA-ISH, regardless of the duration of formalin
      fixation. Based on our results we recommend MP as a reliable and inexpensive
      method to enhance, standardized and simplify RNA-ISH.

PMID- 8857648
TI  - Mixed germ-cell tumor of the brain. Pathologic study of six autopsy cases.
AB  - Intracranial mixed germ-cell tumors are rare. We describe the findings from six
      autopsies of patients with these tumors. The patients were all young at
      presentation (mean age, 16 years), and five of the six were male. Headache,
      vomiting, polyuria and diplopia were common symptoms. Radiographic evaluation
      demonstrated a mass on the midline of the brain. The patients were treated mainly
      with radiation, but survival (mean, 3.7 years) was not as long as predicted. At
      autopsy, the tumors occupied most of the ventricular spaces, and ranged from
      being well-circumscribed to invasive. All tumors contained both germinoma
      components and nongerminomatous germ-cell tumor components. Because the
      distribution of these components was not homogenous, at least two sections were
      necessary for the diagnosis. Immunoreactivity for placental alkaline phosphatase
      was found in all tumors. Immunostaining for human chorional gonadotropin, alpha
      fetoprotein and carcinoembryonic antigen was usually associated with abnormally
      high serum levels of these tumors markers in life. A number of the cells in both
      kinds of tumor components expressed proliferating cell nuclear antigen, probably
      reflecting the intense malignant potential.

PMID- 8857649
TI  - Double sarcomatoid carcinomas of the oesophagus.
AB  - Sarcomatoid carcinoma of the oesophagus is uncommon. A case of double sarcomatoid
      carcinomas was identified in the oesophagus of a 48-year-old man. This is the
      fourth case of multiple primary sarcomatoid carcinomas of the oesophagus and the
      first case with detailed pathological features presented. The clinicopathological
      features of multiple primary tumours and sarcomatoid carcinoma of the oesophagus
      are also reviewed.

PMID- 8857650
TI  - Carcinoma arising in ectopic hamartomatous thymoma. An ultrastructural study.
AB  - We present the ultrastructural features of a case of adenocarcinoma arising in
      ectopic hamartomatous thymoma in a 31 year old man, in the supraclavicular
      location. The tumor had a cribriform adenomatous component with a granular cell
      quality and mimicked a metastatic carcinoma. Ultrastructurally, the spindle cell
      component revealed clusters of tonofilaments and the tumor cells were attached by
      well developed desmosomes. The cytoplasm of adenocarcinoma cells contained
      peculiar cup-shaped bodies derived from the endoplasmic reticulum wrapped around
      the mitochondria.

PMID- 8857651
TI  - Metastasizing uterine leiomyoma. A case with cardiac and pulmonary metastasis.
AB  - A case of histologically benign cardiac and pulmonary metastases from a uterine
      leiomyoma in a 45-year-old woman is reported. The solitary cardiac tumor
      consisted of five lobules with a stalk attached to the anterior papillary muscle
      of the right ventricle, which occupied the right ventricular cavity and almost
      completely obstructed the pulmonary main trunk in the systolic cycle. Multiple
      small nodules were found throughout both lungs. The cardiac tumor was resected at
      open heart surgery and open lung biopsy of the pulmonary lesion was
      simultaneously performed. Both of them were histologically identical to the
      apparently histologically benign uterine leiomyoma which had been resected five
      years previously. Based on the clinical and laboratory findings, it is postulated
      that antegrade metastases via the venous system resulted in the cardiac
      metastasis from the uterine leiomyoma and the secondary pulmonary metastasis from
      the cardiac tumor. In contrast to the light microscopic findings, ultrastructural
      examination suggested the possibility of malignancy associated with the presence
      of immature smooth muscle cells. This is the first reported case of a so-called
      benign metastasizing leiomyoma occurring in the heart.

PMID- 8857652
TI  - Reestablishment of rabbit gallbladder epithelial cells in collagen gel culture
      and their alterations by cytochalasin B and transforming growth factor beta-1. A
      morphologic study.
AB  - We previously developed a model in which rabbit gall bladder epithelial cells in
      collagen gels proliferated and formed multicellular spherical cysts after 2 to 4
      days. In the present study, we examined in depth the dynamic processes of loss
      and reestablishment of cell polarity of rabbit gallbladder epithelial cells
      isolated and cultured in collagen gel. Six hours after being place in culture,
      the isolated epithelial cells had lost the morphologic features and phenotypic
      markers inherent in the in vivo gallbladder mucosa, and autophagic vacuoles
      appeared transiently, reflecting epithelial cell injury, or remodelling, or both.
      After 12 hours, mucin dots appeared in clumps of epithelial cells and gradually
      became larger, and the epithelial cell clumps were transformed into multicellular
      cysts after 1 to 2 days. The luminal surfaces of the mucin dots (intracytoplasmic
      inclusions or small lumens sealed by several epithelial cells) and multicellular
      cysts were covered by microvilli and presented profiles of mucus glycoprotein and
      carbohydrate residues shared with the in vivo gallbladder mucosa. The presence of
      cellular adhesion structures and the distribution of cellular organelles toward
      the luminal surface implied the reestablishment of epithelial cell polarity. The
      addition of cytochalasin B induced many mucin-positive cytoplasmic inclusions
      covered by microvilli in the epithelial cells of the multicellular cysts, while
      the addition of transforming growth factor beta 1 promoted maturation of the
      multicellular cysts. This short term culture is useful for the analysis of the
      polarity of biliary epithelial cells and for examining disorders in this
      polarity.

PMID- 8857653
TI  - An outcomes assessment of 15 years of patient care experiences in predoctoral
      pediatric dentistry.
AB  - The purpose of this study was to examine the trends in numbers, demographic
      characteristics, and treatment history of pediatric dental patients under the
      care of dental students over the period 1980 through 1994. Data were collected
      for: exams, sealants, surfaces of amalgam, composite resin surfaces, pulpotomies,
      stainless steel crowns, and extractions. Correlations were done across the 15
      year period to determine significant trends over time. During the 15-year period,
      the average number of patient visits required for each student to complete the
      requisite number of patients, declined from 45 appointments to complete 10
      patients in 1980, to 35 visits to complete 13 patients in 1994. Over time, the
      numbers of amalgam surfaces, pulpotomies, extractions and stainless steel crowns
      decreased significantly, while the number of composite resin surfaces increased
      (P < 0.05). Based on a previous outcome assessment that indicated declining
      numbers of procedures performed between 1980 and 1985, the required number of
      patients treated per student was raised from 10 to 13, beginning with the 1986
      class.

PMID- 8857654
TI  - Fluoride levels in whole saliva of preschool children after brushing with 0.25 g
      (pea-sized) as compared to 1.0 g (full-brush) of a fluoride dentifrice.
AB  - Concerns regarding an increased risk of dental fluorosis related to ingesting
      fluoride-containing toothpastes by preschool children have led to recommendations
      to reduce the amount of toothpaste used for young children to a pea-sized amount.
      The purpose of this study was to determine the effect on salivary fluoride levels
      of reducing the amount of toothpaste used in a preschool-age (4-5 years)
      population. Salivary fluoride concentrations were determined for 10 children
      whose teeth were brushed with both 0.25 g and 1.0 g of a fluoridated toothpaste
      on two separate days. Initial salivary fluoride levels following the use of 0.25
      g of toothpaste were less than half of the salivary fluoride concentrations when
      1.0 g of toothpaste was used, and levels returned to baseline more rapidly. The
      reduced salivary fluoride levels when less toothpaste is used may result in a
      reduced efficacy for caries prevention. However, any potential reduction in
      caries prevention may still be outweighed by the risk of increased fluoride
      ingestion with larger amounts of toothpaste in preschool children. The results of
      this study suggest that a reduction in the amount of a fluoridated toothpaste to
      a pea-sized amount be limited only to young children who are at risk of ingesting
      toothpaste.

PMID- 8857655
TI  - The influence of midazolam and nitrous oxide on respiratory depression in
      laboratory rats.
AB  - Midazolam in combination with nitrous oxide (N2O) is a commonly used sedative
      approach for pediatric dental patients. Respiratory morbidity and mortality have
      been reported with midazolam administration, particularly when used in
      combination with other drugs in the absence of supplemental oxygen. Thus, the
      purpose of this investigation was to determine the effect of midazolam alone and
      in combination with N2O on respiration in laboratory rats by measuring arterial
      blood gas levels. Sixty-four Sprague-Dawley rats, weighing 250-320 g, were
      assigned to one of eight groups (eight per group). Groups were allocated based
      upon the dosage of midazolam administered (0, 1.0, 2.0 or 4.0 mg/kg i.p.) and
      exposure to N2O/02 (50%/50%) or room air. Arterial blood was obtained from a
      femoral artery catheter and pH, O2, CO2 (mm Hg), and oxygen saturation (%) were
      determined. Samples were analyzed using a System 1306 pH/Blood Gas Analyzer.
      Baseline arterial blood gasses were obtained for each animal and at 15-min
      intervals following midazolam administration throughout the 45-min experiment.
      Following midazolam administration, animals were placed into a sealed chamber
      through which flowed either N2O or room air. Group comparisons demonstrated that:
      1) arterial CO2 levels increased in midazolam-exposed animals breathing room air,
      but not in those exposed to N2O (P < 0.05), and 2) as expected, N2O/O2-exposed
      animals showed an increase in arterial O2 and a %saturation that was not observed
      in room air groups (P < 0.01). This investigation demonstrated that
      coadministration of N2O/O to midazolam-exposed animals did not result in
      hypercarbia, an early indicator of respiratory depression.

PMID- 8857656
TI  - A survey of the American Academy of Pediatric Dentistry membership: nitrous oxide
      and sedation.
AB  - Issues concerning the use of nitrous oxide (N2O) and sedative agents by pediatric
      dentists in relation to recent changes in sedation guidelines of the American
      Academy of Pediatric Dentistry (AAPD) and the American Academy of Pediatrics
      (AAP) are relatively unexplored. A 48-item questionnaire addressing demographics,
      N2O equipment, N2O use, safety, and personnel was mailed to 2,650 active AAPD
      members in the United States and Canada. The 1,758 (66.3%) responses were
      reviewed and descriptive statistics were obtained using SPSS/PC+ statistics
      package. Results suggest that respondents were representative of the demographics
      of the AAPD membership. The majority of respondents (89%) used N2O, with a
      central delivery system being most popular. The majority (74%) did not use any
      monitors when using N2O alone; 10% did not use monitors when N2O was used in
      combination with other sedative agents. A majority (59%) did not use a time-based
      recording of physiological parameters. In conclusion, a mixed impression was
      found about practitioners' use of N2O and sedative agents, suggesting wide
      variability in practitioner habits related to pharmacologic patient management.

PMID- 8857657
TI  - A comparison of two oral ketamine-diazepam regimens for sedating anxious
      pediatric dental patients.
AB  - This double-blind, crossover study assessed physiology and behaviour following
      administration of two oral ketamine-diazepam sedation regimens (4 mg/kg and 8 mg/
      kg ketamine in conjunction with 0.1 mg/kg diazepam). Clinical success was
      achieved in 50% of sedations with 4 mg/kg and 78% of sedations with 8 mg/kg with
      no significant differences between the two regimens (Fisher's exact test). Within
      the crossover group, clinical success was achieved in 56% of sedations with 4
      mg/kg and 87% of sedations with 8 mg/kg with no significant differences between
      the two regimens (Fisher's exact). Although clinically insignificant, ANOVA
      revealed statistical elevations in blood pressures and heart rates and decreases
      in oxygen saturations (P < 0.05). The 4-mg/kg regimen resulted in more negative
      behavior and less sleep. The 8-mg/kg regimen resulted in less negative behavior
      and more sleep.

PMID- 8857658
TI  - The effectiveness of mandibular infiltration compared to mandibular block
      anesthesia in treating primary molars in children.
AB  - Mandibular infiltration has been routinely avoided in treating mandibular molars
      because of its questionable adequacy. The purpose of our investigation was to
      determine the effectiveness of mandibular infiltration compared with mandibular
      block in treating primary molars in children, and to relate the effectiveness to
      age and type of treatment performed. The study population consisted of 89
      cooperative children, 3 to 9 years old, requiring the same type of treatment on
      contralateral mandibular molars. The half-mouth study design was used. Dental
      procedures included class I and II amalgam restorations, stainless steel crowns,
      formocresol pulpotomies, and extractions. Evaluations of pain and behavior for
      each anesthesia technique and type of treatment were made using sounds, motor,
      and ocular changes indicating pain and the Frankl Behavior Rating Scale.
      Evaluations were made upon probing, rubber dam placement, and during tooth
      preparation and extraction. No statistically significant differences was found
      between the two anesthetic techniques for either behavior or pain when performing
      amalgam or stainless steel crown restorations (P = 0.05). Mandibular infiltration
      was less effective than mandibular block for pulpotomy and extraction (P = 0.05).
      No significant relationship to age as determined by primary or mixed dentition,
      for effectiveness was noticed.

PMID- 8857659
TI  - Salivary factors in children and adolescents with insulin-dependent diabetes
      mellitus.
AB  - To determine whether hyperglycemia in IDDM (insulin-dependent diabetes mellitus)
      could interfere with salivary secretion rates, salivary glucose levels, and
      salivary microbial counts, we studied salivary factors in two groups of children
      and adolescents with IDDM. One study group included 14 children with newly
      diagnosed IDDM )mean age 11 years, SD +/- 2.4 years). Samples of saliva were
      collected on admission to hospital and after 2 weeks on insulin treatment. The
      other study group were 50 IDDM children (mean age 14.4 years, SD +/- 1.7 years,
      mean duration of diabetes 6.2 years, SD +/- 1.4 years) visiting the outpatient
      diabetic clinic. Samples of saliva were collected during two visits,
      approximately 3 months apart. In the newly diagnosed IDDM cases, mean salivary
      glucose level decreased from 54.1 +/- 31.7 mg/l to 35.2 +/- 29.5 mg/l (P = 0.096)
      after beginning insulin treatment. During hyperglycemia, salivary glucose levels
      correlated with mean blood glucose levels for the day concerned (r = 0.65, P <
      0.05). The results suggest that high blood glucose levels can increase salivary
      glucose levels. Stimulated saliva secretion increased significantly from 5.4 +/-
      3.3 ml/5 min to 7.3 +/- 2.6 ml/5 min (P < 0.01) while glucose balance improved.
      In the long-term IDDM cases, salivary flow rates and salivary glucose levels were
      not significantly related to the glycosylated hemoglobin (HbA1) values. Salivary
      glucose levels and salivary secretion rates were inversely correlated (P < 0.05).
      In conclusion, hyperglycemia was observed to be associated with decreased
      salivary secretion and high salivary glucose levels. As a consequence, salivary
      lactobacilli and yeast counts tended to increase.

PMID- 8857660
TI  - The temporomandibular joint in juvenile rheumatoid arthritis: Part II.
      Relationship between computed tomographic and clinical findings.
AB  - A study was undertaken to examine the relationship between the clinical signs and
      symptoms of temporomandibular joint (TMJ) disorder and computed tomographic (CT)
      evidence of destruction of these joints in children afflicted with juvenile
      rheumatoid arthritis (JRA). A thorough clinical examination including
      determination of the craniomandibular index (CMI) was performed on each of 37
      consecutive JRA patients (6-17 years old), who had also received comprehensive
      evaluations of TMJ morphology by axial CT (see Part I, Pediatr Dent, 17:46-53,
      1995). Measures of facial asymmetry (photographic) and mandibular size
      (cephalometric) also were collected. Published norms for mandibular dimensions
      and for prevalences of symptoms and signs of TMJ disorders served as control
      data. Various ANOVA and nonparametric statistical models were used for analysis.
      Average maximal opening was significantly less in the JRA subjects compared with
      the controls, and more than 50% of the JRA children manifested chin deviations or
      vertical disparities between mandibular angle regions, indicating compromised
      mandibular function and form. With the exception of facial asymmetry, however,
      none of the clinical signs or symptoms of TMJ dysfunction were remarkable
      predictors of bony destruction of the TMJ. Subjects with definitive evidence (CT)
      of TMJ destruction (62%) could not be identified reliably by any of the clinical
      measures used here. These findings indicate that clinical examination alone is
      inadequate for detecting condylar degeneration in the TMJ of children with JRA.

PMID- 8857661
TI  - Plasma levels of intranasal midazolam at 0.4 mg/kg and 0.2 mg/kg doses.

PMID- 8857662
TI  - High-flow vascular malformations: literature review and case report.

PMID- 8857663
TI  - Birooted primary canines: report of three cases.

PMID- 8857664
TI  - Monilethrix: a review and case report.

PMID- 8857665
TI  - Chemical characterization of melanins in sheep wool and human hair.
AB  - The color of hair and wool in mammals and feathers in birds is mostly determined
      by the quantity and quality of melanins that are synthesized in follicular
      melanocytes and transferred to keratinocytes. These are two chemically distinct
      types of melanin pigments: the black to brown eumelanins and the yellow to
      reddish pheomelanins. Melanins in sheep wool and human hair of various colors
      were characterized by HPLC methods to estimate 5,6-dihydroxyindole-2-carboxylic
      acid (DHICA)-derived units in eumelanins and benzothiazine units in pheomelanins.
      Melanins were also characterized by spectrophotometric methods after differential
      solubilization in alkalies. It was demonstrated that 1) black wool in Asiatic
      sheep contains eumelanin with the DHICA content similar to black mouse melanin,
      while black to brown melanins from human hair contain much lower ratios of DHICA
      derived units, comparable to the slaty mutation in mice, 2) dark brown to brown
      hair in human contains eumelanin whose chemical properties are indistinguishable
      from those of black hair; 3) dark red wool and red human hair contain pheomelanic
      pigments whose chemical properties are rather different from those of yellow
      pheomelanins in mice, and 4) light brown, blonde, and red hairs in human can be
      differentiated from each other with this methodology.

PMID- 8857666
TI  - Effective elimination of fibroblasts in cultures of melanocytes by lowering
      calcium concentration in TPA depleted medium following geneticin treatment.
AB  - Melanocytes grow well in culture media supplemented with phorbol ester. However,
      phorbol ester is metabolically stable and has prolonged effects on multiple
      cellular responses. Different groups have reported that they could cultivate
      melanocytes without phorbol ester. However, in medium without phorbol esters
      contaminating fibroblasts are often difficult to eliminate. We have developed an
      improved method of eliminating fibroblasts using geneticin in serum free medium
      with bFGF, endothelin-1 and no phorbol ester. Treatment with a low concentration
      of geneticin effectively eliminated contaminating fibroblasts and was not harmful
      to melanocytes if geneticin was added initially in a high calcium media (2 mM)
      followed by a change to a low (0.09 mM) calcium media immediately after removal
      of the geneticin. With this technique we could easily establish pure melanocyte
      culture. This culture method will provide a useful tool for studies on melanocyte
      cellular response without the influence of phorbol ester.

PMID- 8857667
TI  - Composition of mammalian eumelanins: analyses of DHICA-derived units in pigments
      from hair and melanoma cells.
AB  - The proportions in which two eumelanin monomers, namely 5,6-dihydroxyindole-2
      carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI), compose the eumelanin
      polymer are believed to determine properties of the pigment including its color.
      These proportions are, however, not well elucidated for naturally occurring
      eumelanins, largely because of methodological difficulties. In this study we
      estimate the content of DHICA-derived units in mammalian eumelanins using a
      combination of two analytical techniques: 1) quantitation of DHICA-derived
      eumelanin by measuring the yield of pyrrole-2,3,5-tricarboxylic acid (PTCA index)
      and 2) spectrophotometrical quantitation of total (DHI + DHICA) eumelanin at 350
      nm (A350 index). The ratio of PTCA/A350 measured for melanins synthesized from
      DHI and DHICA mixed in various molar proportions correlates well with the content
      of DHICA in synthetic polymers. Using this relationship as a standard curve we
      estimated the proportion of DHICA-derived units in mammalian eumelanins from hair
      and melanoma cells and found it to be much higher in rodent pigments (58.8%
      98.3%; two species, mouse and hamster were examined) as compared to human
      eumelanins (19.2%-41.8%; one Caucasian and one Oriental individual were
      examined). No relationship between proportion of DHICA-derived units in eumelanin
      and hair color is found. The latter seems to be determined predominantly by the
      ratio of pheo- to eumelanin synthesis.

PMID- 8857669
TI  - Monoclonal antibody MAT-1 against human tyrosinase can detect melanogenic cells
      on formalin-fixed paraffin-embedded sections.
AB  - Immunohistochemical localization of tyrosinase was examined with a monoclonal
      antibody (MoAb MAT-1) against human tyrosinase on routine formalin-fixed paraffin
      embedded sections of 3 normal skin specimens, 15 melanocytic tumors (6 pigmented
      nevi, 3 juvenile melanomas and 6 malignant melanomas) and 3 non-melanocytic
      tumors. In the melanotic melanomas, almost all tumor cells were clearly stained
      with the antibody. In the nevocytic nevi, the nevus cells in lower epidermis and
      upper dermis were positive for MoAb MAT-1, but negative in middle and lower
      dermis. All three juvenile melanomas, one amelanotic melanoma, and three non
      melanocytic tumors were entirely negative for MoAb MAT-1. Thus, MoAb MAT-1 could
      recognize the cells with melanogenic activity on routine formalin-fixed paraffin
      embedded sections. However, the staining quality was not adequate for normal
      epidermal melanocytes, indicating that small technical innovations in the
      immunostaining process such as formalin fixation after PBS washing are required.
      Nevertheless, MoAb MAT-1 can be expected to be very useful for identifying
      melanogenic cells on paraffin-embedded sections, because we have to date no other
      antibody available for it.

PMID- 8857668
TI  - Interference by cellular melanin with assay of DNA-protein crosslinks by the
      potassium dodecyl sulfate precipitation method.
AB  - The potassium dodecyl sulfate precipitation method was used to quantify DNA
      protein crosslinks (DPCs) in lysates of melanoma cells exposed to ultraviolet
      radiation. Inducing melanin production in these cells before exposure to
      ultraviolet radiation decreased the apparent yield of DPCs. The decrease could
      also be produced by addition of melanin to lysates after exposure to crosslinking
      conditions. Experimental models could attribute this decrease to neither
      quenching of scintillations from the tritium label used nor to an effect of
      single strand breaks of DNA. This assay appears to be inappropriate for
      quantification of DPCs in melanized cells.

PMID- 8857670
TI  - Activation of tyrosinase reduces the cytotoxic effects of the superoxide anion in
      B16 mouse melanoma cells.
AB  - Tyrosinase may protect against oxidative stress by using the superoxide anion (O2
      1.) in the production of melanin. We have examined this by comparing its
      cytotoxic effects in B16/F10 and B16/F10-differential deficient (-DD) mouse
      melanoma cells that express high and low levels of tyrosinase activity
      respectively. Xanthine oxidase (XO) was used to generate O2.1 and cytotoxicity
      assessed by measuring cell survival. XO increased O2.- concentrations and 3 h
      later dose related decreases in cell survival were seen. F10 cells were more
      resistant to these cytotoxic effects than the F10-DD cells. [Nle4, DPhe7]MSH
      increased tyrosinase activity and melanin content, reduced O2.- concentration and
      increased the resistance of F10 cells to the cytotoxic effects of O2.-. No such
      effects were seen in F10-DD cells. The effect of [Nle4, DPhe7]MSH on the
      resistance of the F10 cells was time-dependent and noticeable when tyrosinase
      activity but not melanin was increased. This suggests that it was the activation
      of tyrosinase rather than the increase in the melanin that provided the
      protection against O2.-. In support of this, inhibition of tyrosinase with
      phenylthiocarbamide reduced the increased resistance induced by [Nle4, DPhe7]MSH.
      Moreover, although melanin was capable of scavenging O2.- it had little effect at
      concentrations comparable to those in the activated F10 cells. XO also increased
      the melanin content of F10 but not F10-DD cells. We conclude that tyrosinase is
      able to utilise O2.- to produce melanin and this provides pigment cells with a
      unique anti-oxidant mechanism.

PMID- 8857671
TI  - Tumor suppressor p53 down-regulates tissue-specific expression of tyrosinase gene
      in human melanoma cell lines.
AB  - Tyrosinase, the key gene in melanin pigment synthesis, is tissue-specifically
      expressed in melanocytic cells. Expression of this gene is regulated by various
      hormones, carcinogens, and environmental factors. The molecular basis underlying
      tyrosinase gene regulation is still not clear. In this report, we present the
      effects of tumor suppressor p53 protein in tyrosinase gene expression and melanin
      synthesis in human melanoma. After stable transfection of wild type p53
      expression plasmid into a highly pigmented melanoma cell line, overexpression of
      wt p53 suppressed the pigmentation of the melanoma cells. The loss of
      pigmentation was associated with the loss of endogenous tyrosinase expression at
      the activity and mRNA levels. In order to determine whether the p53 repression of
      tyrosinase mRNA involved modulation of tyrosinase promoter activity, transient
      transfection approaches involving p53 expression plasmid and construct containing
      chloramphenicol acetyl transferase (CAT) reporter gene linked to 270 bp tissue
      specific tyrosinase promoter have been used. p53 specifically repressed CAT gene
      expression from the tyrosinase promoter and not from the Rous sarcoma virus
      promoter. These data suggest that in human melanoma p53 down-regulates the tissue
      specific expression of tyrosinase gene and subsequent melanin synthesis.

PMID- 8857672
TI  - Enzymatic and non-enzymatic oxygenation of tyrosine.
AB  - Tyrosinase isolated from cultured human melanoma cells was studied for tyrosine
      oxygenation activity. L-Tyrosine and D-tyrosine were used as substrates and dopa
      was measured with HPLC and electrochemical detection as the product of
      oxygenation. Incubations were performed in the presence or absence of dopamine as
      co-substrate. Oxygenation of L-tyrosine occurred only in the presence of dopamine
      as co-substrate. No oxygenation of D-tyrosine was found, and we conclude that
      human tyrosinase is characterised by exclusive specificity for the L-isomer of
      tyrosine in its oxygenase function. It has recently been suggested that
      superoxide anion is a preferential oxygen substrate for human tyrosinase.
      Incubations were therefore performed with L- and D-tyrosine, human tyrosine, and
      xanthine/xanthine oxidase in the system, generating superoxide anion and hydrogen
      peroxide. Considerable formation of dopa was observed, but the quantity was the
      same irrespective of whether D-tyrosine or L-tyrosine was used as the substrate.
      Furthermore, formation of dopa occurred in a xanthine/xanthine oxidase system
      when bovine serum albumin (BSA) was substituted for tyrosinase. Our results
      provide no evidence that superoxide anion is an oxygen substrate for human
      tyrosinase. In the incubate containing xanthine/xanthine oxidase, catalase
      completely inhibited dopa formation, and superoxide dismutase and mannitol each
      strongly inhibited dopa formation. The results are compatible with hydroxyl
      radicals being responsible for the formation of dopa, since such radicals may be
      secondarily formed in the presence of superoxide anion and hydrogen peroxide.

PMID- 8857673
TI  - Characterization of the reflective materials and organelles in the bright irides
      of North American blackbirds (Icterinae).
AB  - The reflective materials in the iris stroma of bright-irised American blackbirds
      (Icterinae, Emberizidae) and the red-eyed vireo (vireo olivaceus) (Vireonidae)
      were characterized using high-performance liquid chromatography (HPLC) and diode
      array detection. Two purines, guanine and hypoxanthine, and two pteridines,
      leucopterin and xanthopterin, were detected in large amounts in all bright
      irides. The brown iris of the red-winged blackbird (Agelaius phoeniceus) by
      comparison contained only small amounts of these and additional unidentified
      compounds. The absolute and relative amounts of light-absorbing compounds in the
      iris varied somewhat among species of blackbirds with bright irides, and markedly
      within one species (brewer's blackbird, Euphagus cyanocephalus) between sexes and
      age classes that very in eye color. Differences in the types, numbers, and sizes
      of pigment organelles in the irides appeared to underlie the differences in
      amounts of light-absorbing compounds. Guanine was the most abundant light
      absorbing compound in all bright irides, accounting for about 90% of the total
      absorption at 250 nm. A wide range of concentrations of guanine, from 96 to 9
      micrograms per iris, produced bright irides. The primary pigment organelles of
      pigment cells in bright irides were reflecting platelets, which typically
      appeared as open spaces on electron micrographs. In the red-eyed vireo there were
      in addition red pterinosome-like pigment organelles in the pigment cells on the
      anterior surface of the iris stroma. Guanine was present even in irides with no
      overt reflecting platelets.

PMID- 8857674
TI  - Sterno-laparotomy and extracorporeal circulation for liver transplantation after
      repeat-surgery for Budd-Chiari syndrome.
AB  - The surgical management of two patients undergoing living transplantation for
      Budd-Chiari syndrome is reported. Mesenteriocaval shunt had previously been
      performed in both cases, followed by transcaval liver resection and hepatoatrial
      anastomosis after 3 and 5 years, respectively. Liver transplantation was
      necessitated by deteriorating liver function with portal hypertension and
      recurrent bleeding. The successful operation was performed via sternolaparotomy.
      Atrioatrial anastomosis was constructed during cardiopulmonary bypass,
      considerably simplifying the technical procedure and dramatically reducing blood
      loss.

PMID- 8857675
TI  - Release of interleukin-8 and calprotectin during and after paediatric
      cardiopulmonary bypass with and without ultrafiltration.
AB  - Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and
      subsets and influence of extracorporeal ultrafiltration were evaluated during and
      after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery
      for congenital heart anomalies. Ultrafiltration was used in nine cases and nine
      were controls. Calprotectin concentration rose after start of CPB, peaking 48
      hours postoperatively, with no significant intergroup difference. Positive
      correlation was found between duration of CPB and calprotectin (peak level and
      accumulated total). Circulating IL-8 was detected in all patients
      perioperatively, peaking at wound closure in the ultrafiltration group and at
      termination of bypass in the controls. CPB duration correlated significantly to
      peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples
      contained IL-8 at levels similar to the plasma concentration. Changes in white
      cell counts were mainly attributable to neutrophils. The two subgroups did not
      differ significantly in neutrophil counts. Neutropenia found after 10 minutes of
      CPB was replaced by neutrophilia, with maximal values postoperatively.
      Calprotectin and IL-8 thus were released into the circulation during CPB in
      children. Ultrafiltration did not affect the plasma concentrations of these
      substances, and only IL-8 was detected in the ultrafiltrate.

PMID- 8857676
TI  - Depressed thyroid function following paediatric cardiopulmonary bypass:
      association with interleukin-6 release?
AB  - Cellular activation with release of cytokines such as interleukin-6 (IL-6) occurs
      during cardiopulmonary bypass. IL-6 regulates a number of physiologic processes,
      and a possible role of IL-6 was recently postulated in the pathogenesis of
      changes in serum thyroid hormone concentrations in patients with nonthyroidal
      illness. The perioperative concentrations of triiodothyronine (T3) and IL-6 were
      determined in ten children undergoing open-heart surgery. Significant fall in T3
      concentration was found postoperatively, while IL-6 increased significantly,
      peaking 2 hours postoperatively. The total accumulated IL-6 level 2 hours
      postoperatively was correlated to postoperative T3 concentration. A significant
      inverse correlation was found between T3 levels 24 and 48 hours postoperatively
      and total accumulated IL-6, and also between the percentage decrease in T3
      concentrations and total accumulated IL-6. IL-6 release thus correlated inversely
      to T3 levels after cardiopulmonary bypass.

PMID- 8857677
TI  - Blood cardioplegia does not increase haemolysis. A comparison between crystalloid
      and blood cardioplegia in coronary artery bypass grafting.
AB  - To study the effect of cardioprotection type on haemolysis, 100 patients
      scheduled for elective coronary artery bypass grafting were allocated to receive
      either blood cardioplegia (BCP) or crystalloid cardioplegia (CCP). Haemoglobin
      concentrations in plasma and urine were measured after induction of anaesthesia,
      1 hour postoperatively and the next morning; blood acid-base status was
      determined at the end of cardiopulmonary perfusion; serum electrolytes and
      creatinine were measured before and 1 and 3 hours after the operation and serum
      creatinine also the next morning. Plasma haemoglobin values tended to be higher
      in the CCP than in the BCP group (47.6, 200.2 and 69.1 vs 31.5, 207.5 and 39.2
      mg/l, p = 0.084). The urinary haemoglobin concentrations did not differ between
      the groups. The acid-base status showed greater buffer capacity with BCP
      technique. These results contradict association of blood cardioplegia technique
      with increased haemolysis during coronary artery bypass grafting.

PMID- 8857678
TI  - Diabetes mellitus and morbidity and mortality risks after coronary artery bypass
      surgery.
AB  - Of 1025 patients (912 men, 113 women) who underwent coronary artery bypass
      grafting and were followed up for a mean of 7.4 years, 45 (4.4%) had diabetes
      mellitus. Norwegian population is 1.8-2%). Early mortality was not significantly
      greater among diabetics than in non-diabetics (2.2 vs. 3.1%, odds ratio--OR-0.44,
      confidence interval--CI- 0.05-3.56). Diabetic patients had no increased risk of
      perioperative myocardial infarction (OR = 0.87, CI 0.36-2.10) or of low-output
      syndrome necessitating intraortic balloon pumping (OR = 0.42, CI 0.55-3.05), and
      no excess incidence of late non-fatal myocardial infarction (relative risk =
      0.69, CI 0.10-1.28) or late chronic heart failure (OR = 2.50, CI 0.5-11.0). Long
      term mortality was increased in the diabetic patients (relative risk 1.87, CI
      1.60-2.14). Thus diabetes did not entail heightened risk of early mortality,
      perioperative myocardial infarction or low-output syndrome. Nor was there excess
      risk of recurrent angina pectoris, late non-fatal myocardial infarction or
      chronic heart failure among the diabetic patients, but the late mortality risk
      was increased.

PMID- 8857679
TI  - Elevated circulating levels of von Willebrand factor and D-dimer in patients with
      heart failure and mechanical prosthesis.
AB  - To test the hypothesis of association between heart failure and altered
      haemostatic balance in patients with a mechanical valve prosthesis, comparisons
      were made between 20 patients with mitral valve replacement and stable chronic
      heart failure (group A), 20 with the same prosthesis but satisfactory
      haemodynamics (group B) and 20 age-matched controls (group C). The left
      ventricular ejection fraction was significantly highest (p < 0.001) in group A.
      The pulmonary artery systolic pressure was also highest in group A (p < 0.001),
      without significant difference between groups B and C. Two group A patients had a
      transient ischaemic attack. The D-dimer plasma concentrations and the antigenic
      and biologic von Willebrand factor activities were significantly greatest in
      group A. Significant correlation was found between the plasma concentrations of
      these activities and pulmonary artery systolic pressure and between D-dimer and
      ejection fraction. Platelet-activating factor was detected only in six group A
      patients. The observed relationship between haemostatic factors and heart failure
      in patients with mechanical heart-valve prosthesis advocates careful evaluation
      of von Willebrand factor and D-dimer in order to prevent embolic events in such
      cases.

PMID- 8857680
TI  - Surgical treatment of acute infective endocarditis at Tartu University Hospital
      1984-1993.
AB  - Acute infective endocarditis was surgically treated in 42 patients (36 male, 6
      female), aged 6-66 (mean 43.9) years. The causal microorganism was identified in
      26 cases (61.9%) and the portal of entry in 12. The main indication for surgery
      was cardiac failure. In 23 cases (54.7%) only the aortic valve was affected. The
      mean NYHA function class was 3.35 preoperatively and 1.85 postoperatively. All
      typical surgical findings were preoperatively recognized at echocardiography.
      Twenty-six ball-type and 16 tilting disk valves were inserted. The early
      mortality was 4.7% (2 cases), due to low cardiac output and bleeding. High early
      postoperative morbidity (23%), possibly resulted from too long interval from
      onset of disease to surgery, viz. 1-18 (mean 6.3) months. It is concluded that
      timely operation for acute infective endocarditis is effective.

PMID- 8857681
TI  - Ten-year survival after resection for lung carcinoma. Effect of blood transfusion
      and tumour stage on outcome.
AB  - The objectives were to evaluate the prognosis in resected lung cancer and to
      observe if perioperative blood transfusion adversely affects the prognosis. Of
      208 patients with resection for lung cancer in 1978-1980, all but five were
      smokers: 127 had squamous cell and 81 non-squamous cell carcinoma. Stage I
      disease was found in 143 patients. (69%), stage II in 18 (9%) and stage IIIa in
      47 (23%). Five-year survival was 52% in stage I, 29% in stage II and 7% in stage
      IIIa tumour; the respective 10-year rates were 37, 19 and 3%. Patients given
      perioperative blood transfusion (n = 95) had poorer prognosis than the non
      transfused patients. According to Cox multivariate analysis, however, the
      relative risk of death was only slightly increased by perioperative transfusion
      (p = 0.07). In patients with stage II or IIIa carcinoma at diagnosis, this
      relative risk was 2.17 and 4.99 times higher than in stage I (p = 0.004 and p =
      0.0001). Long-term survival thus was related to extent of the disease at
      diagnosis rather than to numbers of blood transfusions.

PMID- 8857682
TI  - Clinical experience with minitracheotomy.
AB  - In minitracheotomy, a relatively simple percutaneous technique for tracheal
      cannulation, a small-bore tube is inserted via the cricothyroid membrane to
      provide access to suction removal of excess secretion or aspirated material from
      the tracheobronchial tree. It allows efficient tracheobronchial toilet while
      preserving glottic function and avoiding the disadvantages of conventional
      tracheostomy and endotracheal intubation. The indications for minitracheotomy in
      20 cases were excessive postoperative or postpneumonic secretion (14), difficulty
      with endotracheal suction (5) and acute airway obstruction (1). The only major
      complication was bleeding in one case. Minor bleeding occurred at the incision in
      two cases. The cannula was retained for 3-8 days and removal was followed by
      closure within 48 hours. There were no adverse laryngeal effects. Minitracheotomy
      was well tolerated by the patients and is a useful adjunct for removal of airway
      secretion and hospitalized patients.

PMID- 8857683
TI  - Unilateral Fontan operation for tricuspid atresia.
AB  - A 12-year-old child with tricuspid atresia and acquired hypoplasia of the left
      pulmonary artery was successfully treated with unilateral Fontan operation.
      Angiography at age 2 months had shown a normal left pulmonary artery, and a
      modified Potts shunt was performed. An emergency central shunt was required a
      year later. Reinvestigation 5 years after the initial operation revealed severe
      hypoplasia of the left pulmonary artery.

PMID- 8857684
TI  - Diaphragmatic hernia following transhiatal esophagectomy.
AB  - Transitional esophagectomy (THE) has been advocated as an alternative to the
      classic transthoracic approach. A variety of complications have been previously
      described with THE however, these can be avoided with meticulous detail to its
      technique. We report a patient who developed a complete small bowel obstruction
      secondary to a diaphragmatic hernia following transhiatal esophagectomy.
      Techniques to prevent such a rare complication is described.

PMID- 8857685
TI  - Successful repair of tricuspid regurgitation 46 years after causal blunt trauma.
AB  - Tricuspid regurgitation arising from chest trauma 46 years earlier was
      successfully corrected by valve reconstruction in a 67-year-old man. As the
      merits of valve repair are well established, it can be advocated for traumatic
      tricuspid regurgitation, regardless of the time from the causal injury.

PMID- 8857686
TI  - The impact of health care changes on home health.
AB  - OBJECTIVES: To provide an overview of the economic impact of changes on home care
      services. DATA SOURCES: Published articles and organizational and government
      reports pertaining to home care and health care economics. CONCLUSIONS: In
      general, home care organizations are struggling to survive and retain fiscal
      stability. Understanding the economic impact of change on home care services is
      facilitated by a better understanding of three major components: the insurance
      company, the home health service agency, and the client. IMPLICATIONS FOR NURSING
      PRACTICE: The home health nurse who chose this care setting for role autonomy and
      family-centered direct care must now be concerned about productivity, costs, and
      reimbursement. Oncology nurses need to provide administrators and financial
      officers with the information to provide services in the most cost-effective
      manner, and be advocates for the provision of quality care.

PMID- 8857687
TI  - Role of the oncology nurse in home care: family-centered practice.
AB  - OBJECTIVES: To provide an overview of the role of the oncology nurse in home care
      with emphasis on family-centered practice. DATA SOURCES: Review articles, book
      chapters, and case records. CONCLUSIONS: The expansion of care from the hospital
      to the home has resulted in increasing complexity of cancer care at home. The
      goal of home health care is to initiate, manage, and evaluate the resources
      necessary to promote the patient's optimal level of wellness. The family as the
      unit of care is essential in achieving this goal. IMPLICATIONS FOR NURSING
      PRACTICE: The acuity level and complex needs of cancer patients at home requires
      home care nurses to have a broad knowledge base and to be efficient in high
      technology skills. Competency in family assessment, teaching, counseling,
      supervising and coordinating community and family resources are essential to
      provide effective home care.

PMID- 8857688
TI  - Home infusion therapy.
AB  - OBJECTIVES: To examine issues related to the planning of an effective home
      infusion therapy program and to provide an overview of specific home infusion
      therapies for patients with cancer. DATA SOURCES: Published articles, research
      studies, guidelines, and standards pertaining to infusion therapies. CONCLUSIONS:
      Advances in technology have expanded and increased the scope and success of home
      infusion therapy. Antimicrobial therapy, chemotherapy, pain management, total
      parenteral nutrition, and blood transfusion therapy are commonly administered to
      cancer patients at home. IMPLICATIONS FOR NURSING PRACTICE: A competent and
      experienced nursing staff is the cornerstone of a successful home infusion
      program. Safe provision of infusion therapy and care can be assured through
      selection of appropriate patients, effective patient education, well-defined
      agency policies, and effective coordination of home care services.

PMID- 8857689
TI  - Pain management in home care.
AB  - OBJECTIVES: To provide an overview of pain management of the cancer patient in
      the home setting, including assessment, planning and implementation of care and
      evaluation if interventions. DATA SOURCES: Review articles, research studies, and
      book chapters pertaining to pain management. CONCLUSION: A major concern of
      cancer patients and caregivers is their ability to control the pain at home. With
      competent, consistent care, 24-hour access, and working in collaboration with
      other healthcare professionals, nurses can be a decisive force in maintaining
      patient, comfort, supporting and educating the patient and caregiver at home and
      preventing rehospitalization for pain control. IMPLICATIONS FOR NURSING PRACTICE:
      The goal of achieving effective pain control is one of the greatest challenges
      facing the home, care nurse. Meeting this challenge can decrease patients'
      suffering and relieve caregivers' stress.

PMID- 8857690
TI  - Rehabilitation of the cancer patient at home.
AB  - OBJECTIVES: To provide a framework for considering home nursing care of the
      cancer patient within the context of cancer rehabilitation and to briefly review
      various aspects of cancer rehabilitation. DATA SOURCES: Review articles and
      reference books of current and classic works that discuss cancer rehabilitation.
      CONCLUSIONS: Rehabilitation is an important concept that should transcend cancer
      care in all settings, and one that naturally fits with home care. The effects of
      cancer and cancer treatment on the individual's quality of life, eg,
      psychological and social factors, sexual functioning, nutrition, fitness and
      exercise, symptom management, and physical disabilities are important
      considerations in the rehabilitation needs of persons with cancer. IMPLICATIONS
      FOR NURSING PRACTICE: It is the challenge of the home health nurse to promote
      optimal functioning of cancer patients in their home environment. Assessment of
      the cancer patient's rehabilitation needs, skilled interventions, establishment
      of realistic goals, and coordinating care between members of the rehabilitation
      team are major responsibilities.

PMID- 8857691
TI  - Ethical considerations in home care of the oncology patient.
AB  - OBJECTIVES: To examine the context of home care and the values of providers and
      patients that lead to potential ethical conflicts. To discuss a normative model
      of ethical decision making, and to suggest resources for resolving ethical
      issues. DATA SOURCES: Published articles pertaining to ethical issues and home
      health care. CONCLUSIONS: Home care is a viable and beneficial alternative to
      hospital care for a variety of patients, yet home care can result in unique value
      conflicts between patients and their families, and patients and home care
      providers. Loss of privacy and determining who is in charge are several unique
      areas to home care that can lead to ethical problems. Policies, guidelines, value
      statements, and ethics committees are excellent resources to assist in ethical
      decision-making. IMPLICATIONS FOR NURSING PRACTICE: A workable method or model to
      resolve ethical problems, and resources to assist in ethical decision-making can
      provide home care providers with guidelines to analyze an ethical problem and the
      support to choose and act on the best option.

PMID- 8857692
TI  - Selected issues in quality improvement and risk management.
AB  - OBJECTIVE: To provide an overview of selected issues in quality improvement and
      risk management. DATA SOURCES: Published articles, books, and standards
      pertaining to quality improvement and risk management. CONCLUSION: The changing
      health care environment has intensified the need for monitoring processes of home
      care, patient outcomes, and risk management issues. Quality improvement and risk
      management programs can provide guidelines for the home health staff to impact
      outcomes of patient care and patient and caregiver satisfaction. IMPLICATIONS FOR
      NURSING PRACTICE: Home health care nurses are involved in the evaluation of
      systems, processes, and outcomes. Their involvement in identifying problems,
      providing creative solutions, and successfully implementing systems and processes
      is essential for quality improvement. They also must be knowledgeable of risk
      management and be involved in the identification and resolution of potential
      risks to themselves and their patients.

PMID- 8857693
TI  - Hospice nursing.
AB  - OBJECTIVE: To provide an overview of hospice services provided, and hospices
      affiliated with home health agencies. DATA SOURCES: Published articles, book
      chapters, and organizational standards. CONCLUSION: Hospice programs recognize
      that dying is a part of life that requires a redirection of goals from cure to
      palliation. Hospice nursing practice is the provision of palliative nursing care
      for terminally ill patients and their families, with emphasis on addressing
      physical, psychosocial, emotional, and spiritual needs. IMPLICATIONS FOR NURSING
      PRACTICE: Hospice nurses must expand their scope of practice beyond the walls of
      the hospital and home to provide holistic nursing care in collaboration with
      staff from many disciplines. Hospice nurses need to provide support to the
      patient and family in achieving the quality of life of their choosing.

PMID- 8857694
TI  - Teratogenic potential of cocaine.
AB  - Cocaine has been implicated as a potential cause of congenital abnormalities
      since the mid 1980s. Clinical studies have reported an increased risk of
      cardiovascular and central nervous system abnormalities as well as an increased
      incidence of limb reduction defects and intestinal atresias. The published data
      have not established an unequivocal link between cocaine and these abnormalities.
      The most compelling evidence for the role of cocaine as a teratogen is the
      increased risk of genitourinary tract defects. Although animal models have also
      yielded contradictory conclusions, it is intriguing to note that the
      abnormalities observed in these models are similar to those seen clinically. This
      review summarizes the clinical and basic research relating to the teratogenic
      potential of cocaine.

PMID- 8857695
TI  - The impact of prenatal cocaine exposure: studies of the developing infant.
AB  - This article traces several major phases of research evaluating the development
      of infants exposed to cocaine. Although initial studies focused on the medical
      neurobehavioral status of the neonate, these studies often lacked appropriate
      comparison groups, attention to polydrug use, and follow-up after hospital
      discharge. As studies began to include longer follow-up periods and the types of
      comparison groups necessary to evaluate the unique effects of cocaine versus
      factors such as poverty and polydrug use, the deleterious effects of cocaine
      exposure were not as apparent. Although most early studies focused only on mental
      and motor outcomes, recent studies evaluating learning processes, emotional
      development, and the effects of cocaine-exposed infants' unique caretaking
      environments may provide more detailed descriptions of the outcomes of this
      growing population. This article discusses numerous methodological issues that
      continue to challenge this complex research area and recent research efforts that
      may prove beneficial in guiding future studies.

PMID- 8857696
TI  - Cardiovascular effects of cocaine during pregnancy.
AB  - Cocaine administration during pregnancy results in major maternal cardiovascular
      effects that in some cases exceed those observed in the nonpregnant state. Animal
      studies have shown increases in heart rate and blood pressure and decreases in
      regional organ blood flow. Fetal effects include arterial hypoxemia, increases in
      blood pressure and heart rate, and increases in cerebral blood flow that may be
      related not only to hypertension and hypoxemia, but also to direct effects on
      cerebral blood vessels. Fetal intestinal blood flow is decreased. These effects
      may be related to the clinical consequences of cocaine use during pregnancy.

PMID- 8857697
TI  - The maternal and fetal physiologic effects of nicotine.
AB  - The effects of nicotine are seen in every trimester of pregnancy, from increased
      spontaneous abortions in the first trimester, to increased premature delivery
      rates and decreased birth weights in the final trimester. The birth weight of a
      baby is dependent on two factors: the gestational age of the fetus at the time of
      delivery and the rate of fetal growth. Nicotine has been shown to affect both of
      these factors. Carbon monoxide, also found in tobacco, forms carboxyhemoglobin,
      which inhibits the release of oxygen into fetal tissues. Nicotine readily gains
      access to the fetal compartment via the placenta, with fetal concentrations
      generally 15% higher than maternal levels. The primary metabolite of nicotine,
      cotinine, has a half-life of 15 to 20 hours and serum concentrations that are 10
      fold higher than nicotine; thus, cotinine provides a better index of nicotine
      exposure because of its longer half-life. Nicotine concentrates in fetal blood,
      amniotic fluid, and breastmilk. The fetus and neonate may also have environmental
      tobacco exposure that may be significant. In animal models and humans, nicotine
      increases maternal blood pressure and heart rate, with a concomitant reduction in
      uterine blood flow. An increase in fetal heart rate is also seen, which is
      thought to be caused by catecholamine release. The impact of nicotine on the
      respiratory and central nervous system is also reviewed. In conclusion, the
      physiological effect of tobacco on fetal growth seems to be a culmination of both
      the vasoconstrictive effects of nicotine on the uterine and potentially the
      umbilical artery and the effects on oxygenation by carboxyhemoglobin.

PMID- 8857698
TI  - Exposure of embryonic cells to alcohol: contrasting effects during
      preimplantation and postimplantation development.
AB  - Alcohol is a known teratogen that causes a broad variety of developmental
      anomalies, including fetal growth retardation, craniofacial anomalies, and
      neurological disorders. The etiology of this multiple defect syndrome, known as
      fetal alcohol syndrome, has been studied in animal models that reproduce many of
      the attributes of the human disease. These studies show that ethanol is most
      teratogenic during organogenesis and development of the nervous system. The
      molecular basis of fetal alcohol effects has been further investigated using
      embryo and cell culture systems. Recent studies show that signal transduction
      pathways controlling cell proliferation are perturbed during ethanol exposure.
      Ethanol can induce the release of intracellular calcium stores, which stimulates
      the cell cycle, and it also up-regulates the expression of myc proteins
      associated with cell proliferation. Increased proliferation is advantageous
      during the preimplantation period, but ethanol interference with terminal
      differentiation events within developing tissues during organogenesis may
      underlie alcohol teratogenicity.

PMID- 8857699
TI  - The effect of cocaine on myometrial contractile activity: basic mechanisms.
AB  - Several clinical studies have reported an association between cocaine use in
      pregnancy and preterm labor. The mechanism by which cocaine exerts this effect is
      unclear. Although cocaine stimulates isolated myometrial contractile activity,
      results using whole animal models are conflicting. Although cocaine inhibits
      uterine neuronal and extraneuronal uptake of catecholamines and increases
      circulating levels of catecholamines in experimental animals, it is unlikely that
      facilitation of the alpha-adrenergic pathway is the sole mechanism of cocaine's
      action. Further investigation of possible indirect mechanisms of action including
      altered prostaglandin production, inhibition of beta-adrenergic response, and
      direct effects on intracellular calcium mobilization may lead to enhanced
      understanding of the clinical ramifications of cocaine use during pregnancy.

PMID- 8857700
TI  - Placental transfer of selected substances of abuse.
AB  - The placenta was classically considered a barrier, but in 1957 this notion was
      shattered. This organ is only a selective filter and metabolic site. In this
      review, the placental transfer of the top 17 substances of abuse are analyzed. In
      the National Library of Medicine only 41 papers that documented placental
      transfer of the major substances of abuse could be located, and these data
      excluded approximately one-sixth of the most commonly abused substances.
      Nonetheless, it was possible to evaluate placental transfer of all substances of
      abuse based on their physical chemical properties. It is with despair that it
      must be reported that virtually all substances of abuse freely cross the
      placenta, exposing the embryo/fetus to whatever substances the mother may be
      using.

PMID- 8857701
TI  - The association of cigarette smoking with placenta previa and abruptio placentae.
AB  - Smoking was recognized as having an adverse effect of pregnancy outcome as early
      as the mid 1950s. Smoking is a well recognized risk factor for low birthweight
      infants and has been implicated in preterm birth. The increased risk of both
      placenta previa and abruptio placentae among women who continue to smoke during
      pregnancy, is in general, less well recognized, but supported by numerous
      studies. The purpose of this article is to review the published literature
      dealing with the risk of placenta previa and abruptio placentae in women who
      smoke during their pregnancy.

PMID- 8857702
TI  - Physical activity and risk of cardiovascular disease in middle-aged individuals.
      Recommendations.

PMID- 8857703
TI  - Effects of wetsuit use in swimming events. Practical recommendations.

PMID- 8857705
TI  - Significance of the velocity at VO2max and time to exhaustion at this velocity.
AB  - In 1923, Hill and Lupton pointed out that for Hill himself, 'the rate of oxygen
      intake due to exercise increases as speed increases, reaching a maximum for the
      speeds beyond about 256 m/min. At this particular speed, for which no further
      increases in O2 intake can occur, the heart, lungs, circulation, and the
      diffusion of oxygen to the active muscle-fibres have attained their maximum
      activity. At higher speeds the requirement of the body for oxygen is far higher
      but cannot be satisfied, and the oxygen debt continuously increases'. In 1975,
      this minimal velocity which elicits maximal oxygen uptake (VO2max) was called
      'critical speed' and was used to measure the maximal aerobic capacity (max Eox),
      i.e. the total oxygen consumed at VO2max. This should not be confused with the
      term 'critical power' which is closes to the power output at the 'lactate
      threshold'. In 1984, the term 'velocity at VO2max' and the abbreviation 'vVO2max'
      was introduced. It was reported that vVO2max is a useful variable that combines
      VO2max and economy into a single factor which can identify aerobic differences
      between various runners or categories of runners. vVO2max explained individual
      differences in performance that VO2max or running economy alone did not.
      Following that, the concept of a maximal aerobic running velocity (Vamax in
      m/sec) was formulated. This was a running velocity at which VO2max occurred and
      was calculated as the ratio between VO2max (ml/kg/min) minus oxygen consumption
      at rest, and the energy cost of running (ml/kg/sec). There are many ways to
      determine the velocity associated with VO2max making it difficult to compare
      maintenance times. In fact, the time to exhaustion (tlim) at vVO2max is
      reproducible in an individual, however, there is a great variability among
      individuals with a low coefficient of variation for vVO2max. For an average value
      of about 6 minutes, the coefficient of variation is about 25%. It seems that the
      lactate threshold which is correlated with the tlim at vVO2max can explain this
      difference among individuals, the role of the anaerobic contribution being
      significant. An inverse relationship has been found between tlim at vVO2max and
      VO2max, and a positive one between vVO2max and the velocity at the lactate
      threshold expressed as a fraction of vVO2max. These results are similar for
      different sports (e.g. running, cycling, kayaking, swimming). It seems that the
      real time spent at VO2max is significantly different from an exhaustive run at a
      velocity close to vVO2max (105% vVO2max). However, the minimal velocity which
      elicits VO2max, and the tlim at this velocity appear to convey valuable
      information when analysing a runner's performance over 1500m to a marathon.

PMID- 8857704
TI  - Biomechanics and running economy.
AB  - Running economy, which has traditionally been measured as the oxygen cost of
      running at a given velocity, has been accepted as the physiological criterion for
      'efficient' performance and has been identified as a critical element of overall
      distance running performance. There is an intuitive link between running
      mechanics and energy cost of running, but research to date has not established a
      clear mechanical profile of an economic runner. It appears that through training,
      individuals are able to integrate and accommodate their own unique combination of
      dimensions and mechanical characteristics so that they arrive at a running motion
      which is most economical for them. Information in the literature suggests that
      biomechanical factors are likely to contribute to better economy in any runner. A
      variety of anthropometric dimensions could influence biomechanical effectiveness.
      These include: average or slightly smaller than average height for men and
      slightly greater than average height for women; high ponderal index and
      ectomorphic or ectomesomorphic physique; low percentage body fat; leg morphology
      which distributes mass closer to the hip joint; narrow pelvis and smaller than
      average feet. Gait patterns, kinematics and the kinetics of running may also be
      related to running economy. These factors include: stride length which is freely
      chosen over considerable running time; low vertical oscillation of body centre of
      mass; more acute knee angle during swing; less range of motion but greater
      angular velocity of plantar flexion during toe-off; arm motion of smaller
      amplitude; low peak ground reaction forces; faster rotation of shoulders in the
      transverse plane; greater angular excursion of the hips and shoulders about the
      polar axis in the transverse plane; and effective exploitation of stored elastic
      energy. Other factors which may improve running economy are: lightweight but well
      cushioned shoes; more comprehensive training history; and the running surface of
      intermediate compliance. At the developmental level, this information might be
      useful in identifying athletes with favourable characteristics for economical
      distance running. At higher levels of competition, it is likely that 'natural
      selection' tends to eliminate athletes who failed to either inherit or develop
      characteristics which favour economy.

PMID- 8857707
TI  - Tennis elbow. Current concepts of treatment and rehabilitation.
AB  - Tennis elbow occurs as a result of repetitive microtrauma to the musculotendinous
      unit causing inflammatory and degenerative tissue damage. A good understanding of
      the aetiology and pathoanatomy will aid the clinician in preventing and
      recognising this condition. Early recognition with a quality rehabilitative
      programme, and the judicious use of surgical intervention usually results in full
      recovery and excellent functional outcomes.

PMID- 8857709
TI  - Guidelines for physicians with patients on IFN beta-1b: the use of an assay for
      neutralizing antibodies (NAB)

PMID- 8857706
TI  - Carnitine and physical exercise.
AB  - Carnitine plays a central role in fatty acid (FA) metabolism. It transports long
      chain fatty acids into mitochondria for beta-oxidation. Carnitine also modulates
      the metabolism of coenzyme-A (CoA). It is not surprising that the use of
      supplementary carnitine to improve physical performance has become widespread in
      recent years, although there is no unequivocal support to this practice. However,
      critical reflections and current scientific-based knowledge are important because
      the implications of reduced or increased carnitine concentrations in vivo are not
      thoroughly understood. Several rationales have been forwarded in support of the
      potential ergogenic effects of oral carnitine supplementation. However, the
      following arguments derived from established scientific observations may be
      forwarded: (i) carnitine supplementation neither enhances FA oxidation in vivo or
      spares glycogen or postpones fatigue during exercise. Carnitine supplementation
      does not unequivocally improve performance of athletes; (ii) carnitine
      supplementation does not reduce body fat or help to lose weight; (iii) in vivo
      pyruvate dehydrogenase complex (PDC) is fully active already after a few seconds
      of intense exercise. Carnitine supplementation induces no further activation of
      PDC in vivo; (iv) despite an increased acetyl-CoA/free CoA ratio, PDC is not
      depressed during exercise in vivo and therefore supplementary carnitine has no
      effect on lactate accumulation; (v) carnitine supplementation per se does not
      affect the maximal oxygen uptake (VO2max); (vi) during exercise there is a
      redistribution of free carnitine and acylcarnitines in the muscle but there is no
      loss of total carnitine. Athletes are not at risk for carnitine deficiency and do
      not have an increased need for carnitine. Although there are some theoretical
      points favouring potential ergogenic effects of carnitine supplementation, there
      is currently no scientific basis for healthy individuals or athletes to use
      carnitine supplementation to improve exercise performance.

PMID- 8857708
TI  - Cut-off effects in biological activities of surfactants.
AB  - In the homologous series of long hydrocarbon chain surface active compounds,
      their various biological activities increase progressively with increasing chain
      length up to a critical point, beyond which the compounds cease to be active. The
      paper reviews several hypotheses of this cut-off effect in biological activities
      and experimental evidences supporting them. It is suggested that the lateral
      expansion of the phospholipid bilayer of biological membranes caused by the
      intercalation of long-chain amphiphile molecules between the phospholipid
      molecules and the mismatch between their hydrocarbon chain lengths results in the
      creation of free volume in the bilayer hydrophobic region. The elimination of the
      free volume via the hydrocarbon chain trans-gauche isomerisation or
      interdigitation results in the bilayer thickness change or in its destabilisation
      and formation of non-bilayer phase(s). In combination with the partition and
      ionisation equilibria of amphiphiles in the lipid/aqueous phase systems, the free
      volume predicts similar chain length and pH dependencies as observed in
      biological experiments. It is suggested that the free volume mechanism, in
      combination with other mechanisms, could be responsible for the cut-off effects
      in biological activities of amphiphiles.

PMID- 8857710
TI  - Ethical use of placebos and provocative testing in diagnosing nonepileptic
      seizures.

PMID- 8857711
TI  - Classification of daily and near-daily headaches: field trial of revised IHS
      criteria.
AB  - Primary chronic daily headache can be subdivided into transformed migraine,
      chronic tension-type headache, hemicrania continua, and new daily persistent
      headache. We proposed and tested criteria in 150 consecutive outpatients with
      chronic daily headache. Based on preliminary analysis, we revised the criteria
      for transformed migraine. Using the International Headache Society criteria, 43%
      of the patients could not be classified; using our old criteria, 25% could not be
      classified; however, using our new criteria, we were able to classify 100%.
      Seventy-eight percent had transformed migraine, 15.3% had chronic tension-type
      headache, and 6.7% had other headache disorders.

PMID- 8857712
TI  - Neuropsychiatric aspects of Alzheimer's disease: the cholinergic hypothesis
      revisited.
AB  - Altered cholinergic function is a prominent feature of AD. The neuropsychological
      impairments of AD are attributed, at least partially, to the cholinergic
      disturbance, and current approaches to treatment of the cognitive abnormalities
      attempt to enhance cholinergic function. Behavioral changes are common in AD and
      include psychosis, agitation, depression, anxiety, personality alterations, and
      neurovegetative changes. The contribution of the cholinergic deficiency to the
      behavioral alterations has been little explored, but neurochemical,
      neuroanatomic, pharmacologic, and clinical observations suggest that the
      cholinergic deficiency contributes importantly to the neuropsychiatric dimension
      of AD. Investigation of the role of cholinergic dysfunction in the behavioral
      changes of AD will improve understanding of the pathophysiologic basis of these
      abnormalities and may lead to new types of therapy for the neuropsychiatric
      disturbances associated with this common dementing disorder.

PMID- 8857713
TI  - Evolving stroke and the ischemic penumbra.

PMID- 8857714
TI  - Neutralizing antibodies during treatment of multiple sclerosis with interferon
      beta-1b: experience during the first three years. The IFNB Multiple Sclerosis
      Study Group and the University of British Columbia MS/MRI Analysis Group.
AB  - Evidence of diminution of therapeutic efficacy in 35% of interferon beta-1b
      (IFNB)-treated multiple sclerosis (MS) patients who developed neutralizing
      antibodies (NABs) led to extensive study of the effects of NABs on therapeutic
      benefits, side effects, and magnetic resonance imaging (MRI) data. First, we
      validated the IFNB NAB assay used in the multicenter trial by having
      representative stored serum samples reanalyzed by an independent laboratory. When
      NABs developed (as defined), usually in the first year, the exacerbation rates
      after 18 months resembled placebo rates, the numbers of enlarging MRI lesions
      significantly increased compared with those in NAB-negative patients, and there
      was increased new lesion formation in the MRI (p = 0.067). However, worsening of
      the mean Expanded Disability Status Scale score in the 8-MIU treatment arm was
      higher in patients who remained NAB-negative in the third year (p = 0.083). NAB
      positive patients were not overrepresented among the noncompleters, or in five
      patients having at least one episode of skin-site necrosis. After 18 months, flu
      like symptoms were about twice as common in NAB-negative as in NAB-positive
      patients, although the frequency did not exceed 21% in any semester. Decisions to
      discontinue IFNB therapy should be made individually based on clinical response
      and a positive titer of NABs in the serum with the use of a reliable assay. ELISA
      and Western blot techniques measure binding antibodies, not NABs specifically,
      and are unsuitable for use. Possible, but as yet unproven, means of dealing with
      NAB positivity should be studied in properly designed trials. IFNB-1b remains an
      effective therapy for a majority (65%) of MS patients having relapses. The annual
      exacerbation rates in NAB-negative patients receiving the 8-MIU dosage regimen
      are about 50% of those seen in untreated patients, a greater reduction than the
      one-third reduction earlier reported for the entire high-dose arm, and a
      meaningful treatment benefit.

PMID- 8857715
TI  - Linomide reduces the rate of active lesions in relapsing-remitting multiple
      sclerosis.
AB  - The synthetic immunomodulator Linomide, a quinoline-3-carboxamide, has a profound
      inhibitory influence in several experimental autoimmune diseases, including acute
      and chronic experimental allergic encephalomyelitis. In a double-blind trial, 31
      patients with relapsing-remitting multiple sclerosis were randomized to oral
      doses of 2.5 mg Linomide or placebo once a day for six months. Fourteen patients
      receiving Linomide and 14 receiving placebo completed the trial, and the results
      were based on this population. The mean number of active (new and enlarged T2
      weighted) lesions per monthly MRI scan was 1.37 in the patients receiving
      Linomide and 4.22 in the patients receiving placebo (p = 0.043). The percentage
      of scans with active MRI lesions was lower in the Linomide-treated group (p =
      0.0064). When neurologic deficit was assessed by the Regional Functional Scoring
      System (RFSS), the Linomide group showed an improvement of 1% of the maximal RFSS
      range and the placebo group a deterioration of 0.2% (p = 0.14). There were three
      patients with relapses in the Linomide-treated group and six in the placebo group
      (p = 0.22). A slightly decreased proportion of natural killer cells in
      cerebrospinal fluid and peripheral blood was noted in the Linomide group. A
      severe adverse event of pleuropericarditis occurred in one of the Linomide
      treated patients. The most frequent adverse event was musculoskeletal pain, of
      mild to severe degree, which tended to diminish after three months on Linomide
      therapy.

PMID- 8857716
TI  - Malignant supratentorial glioma in the elderly: is radiotherapy useful?
AB  - OBJECTIVES: To determine (1) if radiotherapy (RT) improves survival or neurologic
      function in elderly patients with malignant supratentorial glioma (MSG) and (2)
      which prognostic factors predict survival. BACKGROUND: The prevalence of MSG is
      increasing because both the number of elderly patients and the age-adjusted
      incidence are increasing. Because age is a powerful negative prognostic factor in
      MSG, it is not clear if RT is useful in the elderly. DESIGN/METHODS: We
      retrospectively studied 103 patients from the Southern Alberta Cancer Registry
      diagnosed January 1, 1978, to December 31, 1993, aged 70 yrs, with MSG in whom
      sufficient clinical and follow-up information was available. Multiple treatment
      and patient factors were compared with survival and neurologic function score.
      Diagnosis was confirmed in 15 (14.6%) by biopsy, in 66 (64.1%) by resection, and
      in 22 (21.4%) by clinical course and typical radiographic appearance only.
      RESULTS: All patients died and median survival was 3.9 months. Better neurologic
      function at diagnosis and administration of RT were independently associated with
      significantly longer survivals (p = 0.001 and < 0.001; log rank test). However,
      RT was only associated with longer survival in patients aged less than 80 years.
      Neurologic status only rarely improved following RT. CONCLUSIONS: The prognosis
      for elderly patients with MSG is poor. RT is unlikely to benefit patients who are
      aged 80 years or older. RT has a short-lived benefit for patients who are
      functionally disabled.

PMID- 8857717
TI  - Intramedullary spinal cord metastases: clinical features and treatment outcome.
AB  - Our objective was to delineate clinical features and treatment outcome of
      patients with intramedullary spinal cord metastasis (ISCM). There are no reports
      of a large experience with this rare cancer complication. We reviewed records
      retrospectively from 1980 to 1993 to identify patients with histologically
      confirmed systemic cancer, clinical features of myelopathy, and either tissue
      proven ISCM or abnormal neuroimaging findings consistent with ISCM. We identified
      40 patients who fulfilled these criteria. In nine, ISCM was the initial
      presentation of cancer. Nineteen patients had lung primaries (small cell in 12).
      Twenty-one patients had pain, 35 had demonstrable sensory loss, 37 had weakness,
      and 25 had urinary incontinence at presentation. Nine patients had true Brown
      Sequard syndrome and nine others had pseudo-Brown-Sequard syndrome. Median
      duration of symptoms at diagnosis was 28 days (range 3 days to 18 months).
      Thirteen patients had prior brain metastasis, nine had brain metastasis
      simultaneous with ISCM, and one had brain metastasis after ISCM; 11 had
      concomitant leptomeningeal metastases. Spinal magnetic resonance findings were
      abnormal in 30/30 patients, myelographic results were abnormal in 16/20, and
      eight had pathologic confirmation of ISCM. Thirty-five patients had radiotherapy
      and five had surgery; four were untreated or treated elsewhere. Median survival
      was 4 months for patients receiving radiotherapy and 2 months for patients not
      receiving radiotherapy. Eleven patients survived > 6 months. Twenty-three were
      ambulatory at ISCM diagnosis, and 21 were ambulatory at letest follow-up. We
      conclude that ISCM as the initial presentation of malignancy is not rare, and
      hemicord syndromes occur frequently. Although long-term survival is poor,
      treatment preserves ambulation in most patients still ambulatory at diagnosis.
      Focal radiotherapy is indicated in most patients.

PMID- 8857718
TI  - Long-term prognosis of typical childhood absence epilepsy: remission or
      progression to juvenile myoclonic epilepsy.
AB  - OBJECTIVE: To determine the proportion and characteristics of children presenting
      with childhood absence epilepsy (CAE) who were not taking anti-epileptic drugs
      (AEDs) and were seizure-free over the last year of long-term follow-up. METHODS:
      For case finding, centralized EEG records for the province of Nova Scotia allowed
      identification of all children with typical CAE diagnosed between 1977 and 1985.
      Follow-up was done in 1994 to 1995. RESULTS: Of 81 children with CAE, 72 (89%)
      were contacted for follow-up. Mean age at seizure onset was 5.7 years (range, 1
      to 14 years) and at follow-up was 20.4 years (range, 12 to 31 years). Forty-seven
      (65%) were in remission. Twelve others (17%) were not taking AEDs but continued
      to have seizures. Thirteen (18%) were taking AEDs; five were seizure-free over
      the last year (in four of these a trial without AEDs had previously failed).
      Fifteen percent of the total cohort had progressed to juvenile myoclonic epilepsy
      (JME). Multiple clinical and EEG factors were examined as predictors of outcome.
      Factors predicting no remission (p < 0.05) included cognitive difficulties at
      diagnosis, absence status prior to or during AED treatment, development of
      generalized tonic clonic or myoclonic seizures after onset of AEDs, abnormal
      background on initial EEG, and family history of generalized seizures in first
      degree relatives. CONCLUSIONS: Only 65% of children presenting with CAE had
      remission of their epilepsy. Forty-four percent of those without remission had
      developed JME. At the time of diagnosis, remission is difficult to predict
      accurately in most patients. However, development of generalized tonic-clonic
      seizures or myoclonic seizures during AED treatment is ominous, predicting both
      lack of remission of CAE and progression to JME.

PMID- 8857719
TI  - Is the comorbidity of epilepsy and migraine due to a shared genetic
      susceptibility?
AB  - We tested the hypothesis that the comorbidity of migraine and epilepsy results
      from a shared genetic susceptibility to the two disorders. We used semistructured
      telephone interviews to collect information on migraine and epilepsy in the
      families (parents, siblings, and offspring) of 1,967 adult probands with
      epilepsy. Epilepsy was defined as a lifetime history of two or more unprovoked
      seizures, and migraine as self-reported severe headaches with two or more of the
      following symptoms: unilateral pain, throbbing pain, visual aura, or nausea. As a
      first test of the hypothesis of shared susceptibility, we assessed risk of
      migraine in relatives of probands with genetic versus nongenetic forms of
      epilepsy, using two proxy measures of genetic susceptibility-a first-degree
      family history of epilepsy and idiopathic/cryptogenic (versus postnatal
      symptomatic) etiology. Neither of these two measures was associated with risk of
      migraine in relatives. As a second test, we assessed risk of epilepsy in the
      relatives of probands with versus without migraine. With the exception of one
      subgroup (sons of female probands), risk of epilepsy in relatives was not
      associated with the proband's history of migraine. This pattern of results is
      inconsistent with the hypothesis of a shared genetic susceptibility to migraine
      and epilepsy.

PMID- 8857720
TI  - Treatment of Rasmussen's syndrome with ganciclovir.
AB  - Since cytomegalovirus (CMV) has been implicated in the pathogenesis of
      Rasmussen's syndrome, we treated four patients with ganciclovir, a potent anti
      CMV drug. A 7-year-old girl with seizures escalating to 60/day over 3 months
      despite triple antiepileptic drug therapy became seizure-free 5 days after
      initiation of treatment with no recurrence at 1.5 years follow-up. Focal
      neurologic signs, cognitive function, and the EEG returned to normal. Two
      patients treated 34 and 72 months after disease onset in association with
      epilepsy surgery had a reduction in seizures and one had no response. CMV genome
      was detected in the brains of two of the three patients in whom it was assessed.
      The response to antiviral therapy supports a viral etiology for chronic
      encephalitis of Rasmussen. If the disease is suspected, treatment with
      ganciclovir should be considered as early as possible.

PMID- 8857722
TI  - Motor neuron disease with pyramidal tract dysfunction involves the cortical
      generators of the early somatosensory evoked potential to tibial nerve
      stimulation.
AB  - We evaluated somatosensory evoked potentials (SEPs) to tibial nerve stimulation
      in 39 patients with sporadic motor neuron disease using multiple scalp
      derivations (earlobe reference). SEPs were altered in 22 of 29 amyotrophic
      lateral sclerosis (ALS) patients, whereas they were unaffected in 10 progressive
      muscular atrophy (PMA) patients. The main changes involved the amplitude and the
      field distribution of the early P40 and N37 cortical potentials with different
      modalities varying from a selective loss of the P40 potential (33% of tested
      sides) to absence of all early cortical SEPs (22% of tested sides). The later
      components following N50 were generally spared. The commonly used Cz-Fz montage
      was inadequate for detecting these alterations. Central afferent conduction was
      slightly affected. The selective loss of cortical SEPs and their close
      correlation with clinicoelectrophysiologic evidence of central motor system
      involvement strongly support a cortical origin of the SEP alterations in ALS. We
      suggest that neuronal loss in the somatosensory cortex may selectively affect the
      generator sites of the cortical SEPs to lower limb stimulation.

PMID- 8857721
TI  - Zoster myelitis: improvement with antiviral therapy in two cases.
AB  - This report describes two patients with acquired immunodeficiency syndrome (AIDS)
      and herpes zoster myelopathy. Patient one had a T-8 myelitis that preceded the
      onset of T-8-distribution zoster and was followed by cervical myelopathy.
      Antibody to varicella zoster virus (VZV) was present in the CSF. He never
      received steroids or other immunosuppressive drugs, and his condition improved
      dramatically after treatment with intravenous acyclovir. The second patient had a
      rapidly progressive myelitis with paralysis of both legs. Detection of VZV DNA
      and antibody to VZV in his CSF led to successful treatment with famciclovir
      despite discontinuation of dexamethasone and earlier treatment failure with
      acyclovir. These cases support the idea that VZV myelopathy in the
      immunosuppressed host is caused by virus invasion. CSF analysis for antiviral
      antibody and for VZV DNA by polymerase chain reaction are helpful in establishing
      the diagnosis. Aggressive antiviral therapy is advised.

PMID- 8857723
TI  - Botulinum toxin in severe upper extremity spasticity among patients with
      traumatic brain injury: an open-labeled trial.
AB  - We studied the effect of botulinum toxin A (BTXA) among patients with traumatic
      brain injury (TBI) and severe spasticity unresponsive to conservative management.
      Twenty-one consecutive adult patients with severe spasticity involving the wrist
      and finger flexor musculature were treated with BTXA injection (20 to 40 units
      per muscle) under EMG guidance. After injection, patients received passive range
      of motion (ROM) exercise, with modalities and casting as clinically indicated.
      Outcome measures, including wrist ROM and the modified Ashworth Scale (MAS), were
      assessed 2 to 4 weeks after injection. Among the respective acute and chronic
      groups, mean ROM improved 42.9 (p = 0.001) and 36.2 degrees (p < 0.001). Mean MAS
      rating improved 1.5 (p = 0.01) and 1.47 (p = 0.002) points. There were no
      significant adverse effects. BTXA, in conjunction with conventional modalities,
      significantly improves spasticity and ROM in the distal upper extremity
      musculature of patients with TBI.

PMID- 8857724
TI  - Improvement in the polyneuropathy associated with familial amyloid polyneuropathy
      after liver transplantation.
AB  - OBJECTIVE: To study, following liver transplantation, the neurologic progression
      or regression of the polyneuropathy in a cohort of patients with familial
      amyloidotic polyneuropathy (FAP). BACKGROUND: FAP is characterized by the
      relentless progression of neurologic and cardiac impairment, leading to death
      within 7 to 15 years after disease onset. No effective treatment to slow or halt
      the progression of this disease has been found to date. DESIGN/METHODS: Over the
      past 3 years, our FAP patients were offered liver transplantation as treatment.
      We report on nine patients who were followed longitudinally with serial
      neurologic examinations since transplantation. RESULTS: Clinically, all patients
      evaluated for neurologic progression reported significant improvement in general
      well being. No patient showed any progression in neurologic disease since
      receiving a liver transplant. Improvements are documented in symptomatic,
      autonomic, and sensorimotor neurologic disease in all patients. CONCLUSION: Our
      experience suggests that liver transplantation may offer hope for arrest of
      progression and neurologic improvement in patients with FAP.

PMID- 8857725
TI  - The sensitivity and specificity of anti-GM1 antibody testing.
AB  - Elevated titers of antibodies directed at ganglioside epitopes have been
      associated with multifocal motor neuropathy (MMN), motor variant of chronic
      inflammatory demyelinating polyradiculoneuropathy (CIDP), amyolrophic lateral
      sclerosis (ALS), and other motor neuropathies. Anti-GM1 antibodies were measured
      in 675 patients: 180 age- and sex-stratified healthy blood bank controls, 132
      normal controls who had full neurologic assessment including electromyography,
      121 patients with definite ALS, 19 patients with pure sensory neuropathy, and 173
      consecutive patient serum samples submitted for GM1 antibody testing. Antibodies
      to three ganglioside epitopes were determined by ELISA: IgM and IgG anti
      monosialo GM1, asialo GM1, and disialo GD1b. Antibody titers for normal subjects
      and patients with ALS were used to determine normal values and borderline levels
      below which 99% of normal and 99% of ALS patient titers were found. Clinical
      evaluation of the next 173 consecutive patients referred for anti-GM1 antibody
      testing revealed 36 patients with motor neuropathies. Sera from 18 of these
      patients had titers above the 99% normal threshold and 14 had titers above the
      ALS and normal borderline threshold. All 14 with elevated sera titers were from
      patients with motor neuropathy or neuronopathy. Sixteen patients met the clinical
      and electrophysiologic criteria for MMN; 10 had elevated titers. Ten patients had
      the motor variant of CIDP without conduction block and three had elevated titers.
      Anti-IgM asialo GM1 antibodies had the highest sensitivity and specificity. High
      titer IgM antibodies against monosialo GM1 occurred only in patients with various
      forms of pure motor neuropathy (100% specificity). The sensitivity was 50% for
      this referral-based population.

PMID- 8857726
TI  - Heat-sensitive myotonia in proximal myotonic myopathy.
AB  - Two siblings with proximal myotonic myopathy (PROMM), a hereditary disorder, had
      predominantly proximal weakness, pain, and gait impairment aggravated by warm
      temperatures. EMG of the deltoid showed sparse abnormal spontaneous activity at
      room temperature and with cooling. Warming induced frequent myotonic discharges
      and fibrillations. Profuse myotonia recorded at room temperature in the first
      dorsal interosseous abated following cooling. Repetitive stimulation did not
      reveal a decrement recording from distal muscles, but recording from the deltoid,
      in the one patient tested, revealed a significant decrement that did not improve
      with edrophonium. Myopathic motor units were recorded only in distal musculature.
      The myotonia of PROMM is provoked by heat and diminished by cold and may have a
      different physiologic basis than traditional myotonic syndromes.

PMID- 8857727
TI  - Myotonia and the muscle chloride channel: dominant mutations show variable
      penetrance and founder effect.
AB  - The delayed relaxation or sustained contraction of skeletal muscle-myotonia-is
      frequently seen in myotonic dystrophy and sodium channelopathies (hyperkalemic
      periodic paralysis, paramyotonia congenita). Many cases of congenital myotonia
      without other clinical symptoms have been associated with mutations in the muscle
      chloride channel gene. Most cases reported to date show a recessive inheritance
      pattern, with loss of function of the corresponding protein. Six families have
      been reported with dominantly inherited myotonia and mutations of the chloride
      channel gene. Here we report clinical and molecular data on 38 family members
      from four new families with dominantly inherited myotonia congenita. Three
      families show a previously characterized G230E mutation, and we show that these
      three share a common affected ancestor despite living in different regions of the
      United States (linkage disequilibrium). One Italian family is shown to have a
      novel dominant mutation-I290M. This is the sixth mutation identified in Thomsen's
      myotonia. Genotype/phenotype correlations in these four families showed that both
      of the dominant mutations resulted in a mild clinical picture in 90% of the
      patients, and no symptoms in 10% of mutation-positive patients. The EMG was the
      clinical feature that most closely correlated with mutation data; however, 3 of
      16 (19%) mutation-positive patients tested negative by electromyography at least
      once, and 1 (6%) tested negative despite multiple tests. Only about half (55%) of
      the mutation-positive patients tested positive for percussion myotonia. Most of
      the clinically symptomatic individuals stated that cold temperatures and stress
      substantially worsened their myotonia. Our data show that dominantly inherited
      Thomsen's myotonia is most often a very mild disorder that shows considerable
      clinical heterogeneity.

PMID- 8857728
TI  - Reliability of the NINDS Myotatic Reflex Scale.
AB  - The assessment of deep tendon reflexes is useful for localization and diagnosis
      of neurologic disorders, but only a few studies have evaluated their reliability.
      We assessed the reliability of four neurologists, instructed in two different
      countries, in using the National Institute of Neurological Disorders and Stroke
      (NINDS) Myotatic Reflex Scale. To evaluate the role of training in using the
      scale, the neurologists randomly and blindly evaluated a total of 80 patients, 40
      before and 40 after a training session. Inter- and intraobserver reliability were
      measured with kappa statistics. Our results showed substantial to near-perfect
      intraobserver reliability, and moderate-to-substantial interobserver reliability
      of the NINDS Myotatic Reflex Scale. The reproducibility was better for reflexes
      in the lower than in the upper extremities. Neither educational background nor
      the training session influenced the reliability of our results. The NINDS
      Myotatic Reflex Scale has sufficient reliability to be adopted as a universal
      scale.

PMID- 8857729
TI  - Function changes in spinal muscular atrophy II and III. The DCN/SMA Group.
AB  - The course of spinal muscular atrophy (SMA) is not well established except for
      those patients whose age of onset is before 6 months and who achieve only "sit
      with support" as their maximum function (Werdnig-Hoffmann disease or SMA I). This
      study shows that there is another group of SMA patients whose age of onset and
      maximum function achieved can be used as prognostic guides. Fifty percent of SMA
      patients who could walk without assistance and whose onset was prior to age 2
      years lost the ability to walk independently by age 12. Fifty percent of SMA
      patients who walked and whose onset was between 2 and 6 years of age lost walking
      ability by age 44 years. Fifty percent of SMA patients who could walk with
      assistance as their best function ever achieved lost this ability by age 7 years,
      unrelated to age of onset; none could walk with assistance after age 14 years.
      Seventy-five percent of SMA patients who developed the ability to sit
      independently as their best function were still sitting after age 7 years
      independent of age of onset; 50% of this group could sit independently after age
      14 years. Eighty-five percent of SMA patients who could walk could not negotiate
      stairs without holding onto a rail. They could raise their hands above the head;
      however, as they lost walking ability, they lost this function as well. Only one
      SMA patient whose maximum function was sitting independently could get to the
      sitting position on his own. Only two of these patients could hold their hands
      above their heads. All patients with SMA lose function over time. This function
      loss occurs slowly and is related primarily to maximum function achieved;
      knowledge of age of onset provides helpful information, especially for predicting
      the loss of independent walking.

PMID- 8857730
TI  - The spectrum of familial inclusion body myopathies in 13 families and a
      description of a quadriceps-sparing phenotype in non-Iranian Jews.
AB  - The frequency, patterns of inheritance and clinical phenotypes of inherited
      myopathies with histologic features of rimmed vacuoles, tubulofilamentous
      inclusions and absence of inflammation (familial and hereditary inclusion body
      myopathy [f-IBM]) are poorly defined. Quadriceps sparing is a characteristic of f
      IBM seen in the Iranian Jewish population. Among 101 patients with the feature of
      a red-rimmed vacuolar myopathy, characterized as inclusion body myopathy, seen
      during the last 4 years, we identified 13 families with f-IBM (12.8% frequency
      when one member per family was considered). Five families had an autosomal
      dominant and eight had an autosomal recessive form of inheritance. Among the
      latter group, five patients with early-onset disease (two Caucasian Americans, an
      Asian Indian, and two unrelated Iranian Jews) had the distinct feature of
      quadriceps sparing, which was confirmed by MRI of the thighs. Their disease began
      with weakness and strophy of the foot extensors, forearm flexors, and first
      dorsal interossei muscles and progressed to the forearm flexors, girdle, and
      axial muscles, but spared the quadriceps. Serum CK was normal. Muscle biopsies
      showed rimmed vacuoles, small fibers in groups, amyloid deposition (in one
      patient), tubulofilaments, and no inflammation. Immunocytochemistry did not
      reveal abnormalities of various membrane or cytoskeletal proteins. Major
      histocompatibility complex (MHC) class I antigen was expressed only in a few
      degenerating fibers invaded by macrophages. T-cell infiltrates were not present.
      We conclude that in a large referral population, dominant and recessive
      hereditary and familial forms of IBM are not rare. Quadriceps-sparing myopathy
      appears to be a clinically distinct, autosomal recessive, nonimmune, distal
      vacuolar myopathy that is not limited to Iranian-Jewish ethnic groups.

PMID- 8857731
TI  - Intestinal pseudo-obstruction, myasthenia gravis, and thymoma.
AB  - Two patients presented with abdominal pain, recurrent vomiting, weight loss, and
      constipation secondary to intestinal pseudo-obstruction. Both patients had
      symptoms and signs of myasthenia gravis, acetylcholine receptor antibodies, and
      thymoma. In one patient inflammatory cell infiltrates and occasional degenerate
      neurons were found in the myenteric plexus. The gastrointestinal symptoms
      resolved during treatment with pyridostigmine. The close temporal relationship
      between the onset of the gastrointestinal symptoms and the detection of
      myasthenia gravis and thymoma suggests that intestinal pseudo-obstruction can be
      a paraneoplastic syndrome associated with thymoma.

PMID- 8857732
TI  - Massive leptomeningeal amyloidosis associated with a Val30Met transthyretin gene.
AB  - We report a 69-year-old woman of Mexican origin with a 6-year history of
      progressive paresis, mild peripheral neuropathy, and recent onset of fluctuating
      mental status. Head and spinal MRI revealed contrast enhancing thickened meninges
      which on biopsy disclosed amyloid deposition. Immunohistochemistry identified the
      amyloid as transthyretin (TTR), and polymerase chain reaction/restriction
      fragment length polymorphism analysis of blood revealed a Val30Met mutation in
      one of her TTR genes. This mutation causes familial (hereditary) amyloidotic
      polyneuropathy of the Portuguese type (FAP 1). However, unlike FAP 1, in which
      peripheral neuropathy is a dominant feature, our patient's clinical
      manifestations, which included communicating hydrocephalus and myelopathy, were
      more suggestive of familial oculoleptomeningeal amyloidosis (FOLMA). In summary,
      the clinical presentation of TTR Met 30 mutation is more varied than previously
      suspected, and leptomeningeal amyloidosis should be considered in the
      differential diagnosis of obscure conditions involving meninges.

PMID- 8857733
TI  - Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated
      with dominant and recessive myotonia congenita.
AB  - Myotonia, defined as delayed relaxation of muscle after contraction, is seen in a
      group of genetic disorders that includes autosomal dominant myotonia congenita
      (Thomsen's disease) and autosomal recessive myotonia congenita (Becker's
      disease). Both disorders are characterized electrophysiologically by increased
      excitability of muscle fibers, reflected in clinical myotonia. These diseases are
      similar except that transient weakness is seen in patients with Becker's, but not
      Thomsen's disease. Becker's and Thomsen's diseases are caused by mutations in the
      skeletal muscle voltage-gated chloride channel gene (CLCN1). Genetic screening of
      a panel of 18 consecutive myotonia congenita (MC) probands for mutation in CLCN1
      revealed that a novel Gln-68-Stop nonsense mutation predicts premature truncation
      of the chloride channel protein. Four previously reported mutations, Arg-894
      stop, Arg-338-Gln, Gly-230-Glu, and del 1437-1450, were also noted in our sample
      set. The Arg-338-Gln and Gly-230-Glu mutations were found in patients with
      different phenotypes from those of previous reports. Further study of the Arg-338
      Gln and Gln-230-Glu alleles may shed light on variable modes of transmission
      (dominant versus recessive) in different families. Physiologic study of these
      mutations may lead to better understanding of the pathophysiology of myotonia in
      these patients and of voltage-gated chloride channel structure/function
      relationships in skeletal muscles.

PMID- 8857734
TI  - Intraoperative monitoring of motor evoked potentials: a review of 116 cases.
AB  - We reviewed the results of motor evoked potential (MEP) and somatosensory evoked
      potential (SEP) monitoring during 116 operations on the spine or spinal cord. We
      monitored MEPs by electrically stimulating the spinal cord and recording compound
      muscle action potentials from lower extremity muscles and monitored SEPs by
      stimulating posterior tibial or peroneal nerves and recording both cortical and
      subcortical evoked potentials. We maintained anesthesia with an N2O/O2/opioid
      technique supplemented with a halogenated inhalational agent and maintained
      partial neuromuscular blockade using a vecuronium infusion. Both MEPs and SEPs
      could be recorded in 99 cases (85%). Neither MEPs nor SEPs were recorded in eight
      patients, all of whom had preexisting severe myelopathies. Only SEPs could be
      recorded in two patients, and only MEPs were obtained in seven cases.
      Deterioration of evoked potentials occurred during nine operations (8%). In eight
      cases, both SEPs and MEPs deteriorated; in one case, only MEPs deteriorated. In
      four cases, the changes in the monitored signals led to major alterations in the
      surgery. We believe that optimal monitoring during spinal surgery requires
      recording both SEPs and MEPs. This provides independent verification of spinal
      cord integrity using two parallel but independent systems, and also allows
      detection of the occasional insults that selectively affect either motor or
      sensory systems.

PMID- 8857735
TI  - Effects of stimulus asymmetry on line bisection.
AB  - There is an upward bias in bisecting radial and vertical lines under visual
      guidance. We investigated whether illusory visual factors might contribute to a
      previously reported representational upward bias in this task. In two
      experiments, subjects performed a line-bisection task along the three orthogonal
      axes (horizontal, radial, vertical). In Experiment 1, the stimuli consisted of a
      line terminated at each end by two equal- or different-sized bars. In Experiment
      2, the stimuli were formed by a line terminated by two equal- or different-sized
      directional labels: SOPRA ("top") and SOTTO ("bottom"). The results showed a
      bisection bias towards the smaller bar (Experiment 1) and the smaller directional
      label (Experiment 2) on all three spatial axes, supporting the existence of an
      illusory visual effect. Contrary to a previous report, the data failed to show
      any representational (semantic) bias related to directional label meaning. These
      findings suggest that perceptual/attentional factors play a significant role in
      normal subjects' upward bias.

PMID- 8857736
TI  - Angiotropic large-cell lymphoma with peripheral nerve and skeletal muscle
      involvement: early diagnosis and treatment.
AB  - Angiotropic large-cell lymphoma is a disorder characterized by an intravascular
      proliferation of malignant lymphoid cells. We present a patient with
      polyradiculoneuropathy, myelopathy, and myopathy diagnosed by peripheral nerve
      and muscle biopsy, who was treated and remains in stable neurologic condition.

PMID- 8857737
TI  - Single large-scale mitochondrial DNA deletion in a patient with mitochondrial
      myopathy associated with multiple symmetric lipomatosis.
AB  - In a nonalcoholic woman with multiple symmetric lipomatosis (MSL), muscle
      histochemistry showed ragged-red fibers and cytochrome c oxidase negative fibers.
      Southern blot analysis revealed a single deletion of mitochondrial DNA (mtDNA).
      We suggest that MSL is an uncommon manifestation of the wide clinical spectrum of
      mitochondrial disorders, in particular of those associated with single mtDNA
      deletions.

PMID- 8857738
TI  - Localization of temporal lobe epileptic foci with iodine-123 iododexetimide
      cholinergic neuroreceptor single-photon emission computed tomography.
AB  - There is evidence suggesting that muscarinic cholinergic neuroreceptors (mChR)
      are reduced at seizure foci. Iodine-123 (I-123) iododexetimide (IDEX) single
      photon emission computed tomography (SPECT) permits in vivo imaging of mChR. We
      assessed 23 patients with temporal lobe epilepsy (TLE) undergoing preoperative
      assessment. Regions of interest were placed over the amygdala, hippocampus, and
      lateral temporal cortex on IDEX SPECT images. Eighteen patients had unilateral
      TLE. In these, IDEX binding in the ipsilateral hippocampal region was reduced by
      19.1 +/- 12%. This was significantly greater than blood flow asymmetry (p < 0.02
      by Wilcoxon's signed-rank test). Changes were less marked in the amygdala (11.3
      +/- 6.4%) and lateral cortex (7.6 +/- 12.1%). Blinded visual analysis gave
      correct localization in 14 (78%) patients, and hexamethylpropylenamine oxide
      (HMPAO) SPECT gave correct localization in 50%. MRI revealed hippocampal
      sclerosis in 13 (72%) patients and was normal in 5 patients. Of the latter group,
      four were correctly localized by IDEX. This study confirms that mChR receptors
      are altered in medial temporal lobe structures in TLE. IDEX SPECT appears to be
      superior to interictal HMPAO SPECT and complimentary to MRI for seizure focus
      localization.

PMID- 8857739
TI  - The amygdala and intractable temporal lobe epilepsy: a quantitative magnetic
      resonance imaging study.
AB  - OBJECTIVE: To establish a quantitative MRI technique using T2 relaxation time
      mapping to study systematically the amygdala in patients with intractable
      temporal lobe epilepsy (TLE). BACKGROUND: Identification of a focal abnormality
      on MRI in patients with intractable TLE is important, because outcome from
      surgery depends largely on the removal of the underlying pathology. Hippocampal
      sclerosis (HS) is the most common cause of intractable TLE, but epileptogenic
      lesions can be confined to the amygdala. METHODS: Twenty control subjects and 82
      patients with intractable TLE were studied. Patients who had foreign tissue
      lesions visible on routine MRI were excluded. All subjects had a hippocampal T2
      map and volumetry and an amygdala T2 (AT2) map. RESULTS: Forty-four of the 82
      patients (54%) had an abnormal AT2, which was bilateral in 18. Forty-four
      patients (54%) had unilateral HS on MRI, 25 (57%) of whom had an abnormal AT2.
      Seven patients (8%) had bilateral HS, four of whom had an abnormal AT2. Thirty
      one patients (38%) had normal quantitative hippocampal measures, 15 of whom had
      an abnormal AT2, which was bilateral in seven. Fluid attenuated inversion
      recovery (FLAIR) imaging, where appropriate, confirmed that the increased AT2
      signal was due to parenchymal changes. Neuropathologic correlates of an increased
      AT2 included microdysgenesis in one and gliosis in three patients. Patients with
      an isolated AT2 abnormality were significantly older at the onset of habitual
      epilepsy and rarely had a history of febrile convulsions, in comparison with
      patients who had HS. An isolated AT2 abnormality correlated well with interictal
      EEG findings. CONCLUSIONS: The combination of AT2 mapping and FLAIR is a
      sensitive method to detect lesions that are not seen on routine MRI in the
      amygdalae of patients with intractable TLE. Further correlational studies will be
      required to define the role of this technique in the presurgical evaluation of
      patients with intractable TLE.

PMID- 8857740
TI  - Subregional loss of putaminal efferents to the basal ganglia output nuclei may
      cause parkinsonism in striatonigral degeneration.
AB  - In this study, we examined the topographic involvement of the putaminal
      projection neurons and their axons in the globus pallidus and substantia nigra,
      which we visualized by calcineurin immunostaining, in the basal ganglia of
      patients with striatonigral degeneration (SND). In all cases examined, there was
      a marked decrease in number of calcineurin-immunopositive neurons in the caudal
      and lateral portion of the putamen. Also, marked depletion of calcineurin
      immunoreactive putaminal efferents was consistently present in the
      posteroventrolateral portions of the globus pallidus interna (GPi) and externa,
      and in the ventrolateral portion of the substantia nigra pars reticulata (SNr)
      topographically corresponding to the putaminal lesion. In view of the functional
      model of the basal ganglia "motor" circuit, these findings suggest that
      subregional deafferentation of the GPi/SNr (i.e., basal ganglia output nuclei)
      from putaminal inputs may be responsible for parkinsonism in patients with SND.

PMID- 8857741
TI  - Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease
      patients: dose-response study and correlations with plasma levels.
AB  - OBJECTIVE: To determine if ventricular cerebrospinal fluid (vCSF) alpha
      tocopherol levels in Parkinson's disease (PD) patients can be increased by oral
      alpha-tocopherol supplementation and whether vCSF levels are linearly related to
      plasma alpha-tocopherol levels. BACKGROUND: In spite of its putative
      neuroprotective properties, alpha-tocopherol has failed to alter PD clinical
      progression. However, the ability of supplemental alpha-tocopherol to affect
      brain or vCSF levels has never been assessed in humans nor has a dose response
      curve for alpha-tocopherol in vCSF been established. METHODS: Five PD patients
      with Ommaya catheters received oral dl-alpha-tocopherol over 5 months. Each
      patient ingested alpha-tocopherol daily with monthly dosage increases (400, 800,
      1,600, 3,200, 4,000 IU/day). Plasma and vCSF samples were obtained at baseline
      and at the end of each month. Alpha-tocopherol levels were determined in
      triplicate by high-pressure liquid chromatography with fluorometric and
      electrochemical detection. RESULTS: At baseline, endogenous alpha-tocopherol was
      detected in plasma and vCSF, with a greater than one-hundred-fold difference
      between the fluid compartments (mean plasma level 18.76 microM/l (SD +/- 4.69)
      versus mean CSF level 0.114 microM/l (SD +/- 0.084). A clear dose-response curve
      occurred in plasma, with statistically significant increases over baseline
      developing even with 400 IU/d. With higher doses, a significant increase
      continued without evidence of saturation. However, there was no significant
      increase in vCSF alpha-tocopherol levels at any dose, including the supraclinical
      (4,000 IU/d). There was no correlation between plasma and vCSF alpha-tocopherol
      levels. CONCLUSION: Oral alpha-tocopherol supplementation, even at supraclinical
      doses, fails to increase vCSF alpha-tocopherol levels. This lack of change may be
      due to limited passage across the blood-brain barrier or very rapid alpha
      tocopherol metabolism. All prior negative studies on efficacy of alpha-tocopherol
      in PD may need reevaluation in light of these pharmacologic data.

PMID- 8857742
TI  - Quantitation of epidermal nerves in diabetic neuropathy.
AB  - We describe methods to quantify epidermal nerve fibers (ENFs) in skin biopsy
      specimens from diabetic candidates for pancreas transplantation and control
      subjects. ENFs and the dermal-epidermal basement membrane were stained by
      immunohistochemical methods, imaged with a confocal microscope, and quantified
      using a neuron tracing system. The number of ENFs per surface of epidermis was
      diminished in diabetic subjects. ENF number and summed length of all ENFs per
      volume of epidermis examined were also decreased. Length and number of branch
      points of single surviving ENFs were similar in skin of control and diabetic
      subjects. The methods and results constitute a basis for continued study of the
      effects of the euglycemia that attends successful pancreas transplantation and
      the effects of therapy in patients with various types of polyneuropathy.

PMID- 8857743
TI  - T-cell receptor alpha, beta, gamma, and delta chain gene microsatellites show no
      association with multiple sclerosis.
AB  - Genetic predisposition to multiple sclerosis (MS) is determined, in part, by
      certain HLA genotypes, but the contribution of T-cell receptor (TCR) germline
      polymorphisms to MS susceptibility is less clear. Reports of disease associations
      with restriction fragment length polymorphisms of TCR alpha and beta chain genes
      have been difficult to confirm, and little data is available on the influence of
      the TCR gamma delta germline in MS. We investigated the TCR alpha, beta, gamma,
      and delta chain genes of Northern Irish patients with MS using four
      microsatellite markers of high heterozygosity. There were similar allele
      frequencies in patients and controls for all microsatellites studied. We conclude
      there is no convincing evidence for an association of MS with TCR alpha, beta,
      gamma, and delta chain gene polymorphisms.

PMID- 8857744
TI  - Evidence for a prolonged role of alpha 4 integrin throughout active experimental
      allergic encephalomyelitis.
AB  - The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand,
      vascular cell adhesion molecule 1, appear to be of critical importance in the
      leukocyte trafficking that accompanies CNS damage in experimental allergic
      encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4
      beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease
      reversal up to 1 month following disease onset. Limited treatment with a
      monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant
      decrease in both clinical and histopathologic signs. This was not observed in
      isotype control experiments. In the latter phase of progressive disease,
      widespread demyelination occurred in the animals that did not respond to 6 days
      of anti-alpha 4 treatment. These results demonstrate an essential role for alpha
      4 beta 1 interactions throughout active EAE and illustrate the difference between
      reversible clinical deficits caused by edema and irreversible deficits associated
      with demyelination.

PMID- 8857745
TI  - Amyotrophic lateral sclerosis: oxidative energy metabolism and calcium
      homeostasis in peripheral blood lymphocytes.
AB  - There is evidence of oxidative injury in postmortem brain, spinal cord, and CSF
      of patients with sporadic amyotrophic lateral sclerosis (SALS patients). We
      investigated the oxidative metabolism and calcium homeostasis in peripheral blood
      lymphocytes from such patients and did not find statistical differences in the
      basal oxygen consumption rate (QO2), cytochrome c oxidase activity, catalase
      activity, and lactate production. However the increase in QO2, induced by an
      uncoupler of oxidative phosphorylation, was depressed and the basal (resting)
      level of free cytosolic calcium ([Ca2+]in) was higher in lymphocytes from SALS
      patients (p < 0.01). Further increase in free [Ca2+]in challenged by a K+ channel
      blocker or by an uncoupler of oxidative phosphorylation was similar in SALS and
      control lymphocytes. The results show that systemic changes consistent with the
      presence of mitochondrial and of calcium metabolism dysfunction are present in
      SALS.

PMID- 8857746
TI  - Reduced striatal dopamine receptors in Alzheimer's disease: single photon
      emission tomography study with the D2 tracer [123I]-IBZM.
AB  - Many patients with Alzheimer's disease (AD) develop parkinsonian symptoms,
      suggesting an overlapping between AD and Parkinson's disease (PD). However,
      pathologic and neurochemical studies indicate that the involvement of the
      dopamine system may be different in the two conditions. Using single photon
      emission tomography, we determined the relative specific striatal uptake
      (striatum to cerebellum ratio) of the D2 receptor ligand [123I]-IBZM in 15 AD
      patients without overt extrapyramidal symptoms (three subjects presented mild
      rigidity and bradykinesia) and nine age-matched controls. Mean specific activity
      in striatal regions of AD patients (1.35 +/- 0.09) was significantly reduced from
      control mean (1.59 +/- 0.03). Because such changes were evident even in the
      absence of overt parkinsonian symptomatology, our data indicate that alterations
      of striatal D2 receptors may be part of the pathologic abnormalities of AD. In
      addition, the mechanisms underlying extrapyramidal symptoms in AD (decline of
      postsynaptic striatal dopamine receptors) appear different from the prevalent
      presynaptic nigrostriatal alterations typical of PD.

PMID- 8857748
TI  - Good clinical outcome in a patient with a large CT scan hypodensity treated with
      intra-arterial urokinase after an embolic stroke.
AB  - Hypodense regions demonstrated by CT within 6 hours of the onset of stroke may
      reflect irreversibly damaged tissue, and some have suggested that patients with
      such findings should be spared the risks of thrombolytic therapy since they are
      unable to benefit from it. We report here a patient with a low-density area
      demonstrated by CT less than 6 hours after onset of symptoms who improved
      dramatically after successful intra-arterial thrombolysis.

PMID- 8857747
TI  - Fibroblasts of patients affected by Down's syndrome oversecrete amyloid precursor
      protein and are hyporesponsive to protein kinase C stimulation.
AB  - The present study investigates the ability of the pharmacologic activation of
      protein kinase C (PKC) to modulate amyloid precursor protein (APP) secretion in
      human skin fibroblasts from patients affected by Down's syndrome (DS). We
      assessed DS subjects at the Hospital Institute of Sospiro, Cremona, and at the
      Alzheimer's Disease Unit of the Sacred Heart Hospital in Brescia, and we
      subdivided them into nondemented (NDS) and demented (DDS) patients. All DS
      patients were trisomy 21 karyotype. DS fibroblasts had an increased content of
      APP immunoreactive material as revealed by immunocytochemistry analysis. The
      basal secretion of soluble APP was higher (+94.6%) in Down's cells with respect
      to controls. The observation on the fibroblasts prepared from DS is consistent
      with these patients' possessing an extra copy of the APP gene (mapped on
      chromosome 21) leading to increased APP expression. Phorbol-12,13-dibutyrate
      (PdBu, 9 to 150 nM) treatment promoted a dose-dependent increase of secreted APP
      in the conditioned medium of control fibroblasts. The peak response (+102.2%) was
      attained using 150 nM PdBu. In Down's fibroblasts, PdBu stimulated APP secretion
      already maximally at low concentrations (9 nM), but the peak response, due to the
      higher basal release, was lower on a percentage basis (+16.4%) than in control
      fibroblasts. The results indicate that in Down's fibroblasts the mechanisms
      controlling APP release are at least quantitatively altered. In addition, these
      results suggest caution when using information obtained from Down's patients to
      model Alzheimer's disease biochemical defects.

PMID- 8857749
TI  - Nonconvulsive status epilepticus in thrombotic thrombocytopenic purpura.
AB  - Fluctuating neurologic symptoms, including confusion, stupor, and convulsions,
      are common signs in thrombotic thrombocytopenic purpura (TTP). We describe a
      patient with TTP who had a clinical seizure, intermittent stupor, and a declining
      course despite aggressive treatment. An EEG showed continuous rhythmic
      epileptiform discharges, and she improved with anticonvulsants. Fluctuating
      stupor in TTP has generally been attributed to microvascular occlusive disease,
      but nonconvulsive status epilepticus is a treatable condition that can cause
      similar symptoms.

PMID- 8857750
TI  - Spinal cord venous infarction following endoscopic sclerotherapy for esophageal
      varices.
AB  - The authors report an unusual case of venous infarction of the spinal cord
      associated with endoscopic sclerotherapy for esophageal varices. MR imaging
      findings included signal abnormalities and abnormal enhancement of the affected
      spinal cord and T-8 vertebral body. A review of the hemodynamic changes
      associated with portal hypertension and the normal venous drainage of the spinal
      cord is presented.

PMID- 8857751
TI  - Olanzapine in the treatment of dopaminomimetic psychosis in patients with
      Parkinson's disease.
AB  - We studied the effect of olanzapine (1 to 15 mg/d) in 15 nondemented parkinsonian
      patients with drug-induced psychosis. Psychotic symptoms decreased significantly
      during treatment, and there was no worsening of extrapyramidal symptoms. These
      results suggest that olanzapine is a well-tolerated and effective treatment for
      drug-induced psychosis in nondemented patients with Parkinson's disease.

PMID- 8857752
TI  - Regional subacute cranial neuropathies following internal carotid cisplatin
      infusion.
AB  - The inferolateral trunk arises from the internal carotid artery at C-4 and
      provides vascular supply to cranial nerves III to VI. We report a patient who
      developed neuropathies of cranial nerves III, V1-3, and VI, 48 hours after
      infusion of cisplatin into the right internal carotid artery for an anaplastic
      oligoastrocytoma. The clinical and radiographic findings implicated direct
      toxicity to nerves in the distribution of the inferolateral trunk. We found
      additional cases by review of published brain tumor chemotherapy trials, thus
      identifying a novel, toxic neurovascular mechanism for injury to cranial nerves
      III to VI.

PMID- 8857753
TI  - Anterior choroidal artery aneurysm and stroke.
AB  - We report the unique combination of a mid anterior choroidal artery (AChA)
      aneurysm and ischemic stroke presenting as a movement disorder in a young man.
      The mechanism for stroke in the AChA territory may either reflect a cause or an
      effect of aneurysm formation. We provide evidence for both arguments and
      speculate on the anatomic basis for the initial presentation of hemibody spasm.

PMID- 8857754
TI  - Elevation of cerebral lactate detected by localized 1H-magnetic resonance
      spectroscopy in migraine during the interictal period.
AB  - We used localized 1H-magnetic resonance spectroscopy (MRS) to study the metabolic
      changes in the brains of patients with migraine during the interictal period.
      Measurement of metabolite levels in the occipital visual cortex in six normal
      subjects and six patients disclosed high lactate levels in the five patients who
      had experienced a migraine attack within the previous 2 months. One patient who
      had not experienced a migraine attack in the previous 4 years did not show a
      lactate peak. We speculate that anaerobic glycolysis occurs in the brains of
      patients with migraine during the interictal period, and a long attack-free
      period may normalize the subclinical metabolic disturbance.

PMID- 8857756
TI  - Use of sumatriptan in post-ictal migraine headache.

PMID- 8857755
TI  - Neurology's witness to history: the Combined Intelligence Operative Sub-Committee
      and reports of Leo Alexander.

PMID- 8857757
TI  - Exquisite sensitivity of paroxysmal kinesigenic choreoathetosis to carbamazepine.

PMID- 8857758
TI  - Gabapentin interaction with felbamate.

PMID- 8857759
TI  - Nine families with the SCA3/Machado-Joseph disease type of inherited ataxia.

PMID- 8857760
TI  - Worth of neurologists.

PMID- 8857761
TI  - Worth of neurologists.

PMID- 8857762
TI  - Spinal A-V fistula.

PMID- 8857763
TI  - Risk factors for lacunes.

PMID- 8857764
TI  - IFNB in MS.

PMID- 8857765
TI  - IFNB in MS.

PMID- 8857766
TI  - IFNB in MS.

PMID- 8857767
TI  - Screening for group B streptococcal disease.

PMID- 8857768
TI  - Rural physicians as educators: why take on another job?

PMID- 8857769
TI  - Obtaining credentials for osteopathic manipulative medicine.

PMID- 8857770
TI  - Chiropractic manipulation and incidence of complications.

PMID- 8857771
TI  - A case of inflammatory breast cancer.

PMID- 8857772
TI  - Histamine H2-receptor antagonists and chronic theophylline toxicity.

PMID- 8857773
TI  - Identifying the reasons for increased asthma mortality.

PMID- 8857774
TI  - AAFP position on use of ultrasonography in obstetrics.

PMID- 8857775
TI  - Family planning using the ecologic breast feeding method.

PMID- 8857776
TI  - Solitary metastatic melanoma of the small intestine.

PMID- 8857777
TI  - Practical management of pressure ulcers.
AB  - The use of wound dressings that are based on the principles of moist wound
      healing has recently changed the management of pressure ulcers. These products
      may improve healing rates but also offer improved comfort to the patient, reduced
      dressing time and improved cosmesis. However, healing is unlikely to be achieved
      unless the factors that contribute to ulcer formation are addressed. Principles
      of management include the elimination or reduction of pressure and other
      contributing factors, treatment of infection, appropriate wound management,
      involvement and education of the patient and caregivers, and maintenance of
      healed tissue. It is estimated that 95 percent of all pressure ulcers are
      preventable. Prevention rather than mere treatment of established ulcers remains
      a top priority in the effort to reduce the incidence of this common, complex and
      difficult problem. Use of assessment tools that quantify the primary risk factors
      for the development of pressure ulcers is helpful in predicting and preventing
      compromise of tissue.

PMID- 8857778
TI  - HIV infection in women: an escalating health concern.
AB  - The proportion of women infected with the human immunodeficiency virus (HIV)
      continues to increase. Over one-half of women acquire the virus through
      heterosexual contact. The diagnoses that define the acquired immunodeficiency
      syndrome and the use of antiretroviral therapy are similar in men and women,
      except in pregnancy. However, management decisions differ significantly regarding
      contraceptive and gynecologic care. Besides abstinence, use of the latex condom
      continues to be the most effective way of preventing transmission of HIV. The
      management of human papillomavirus-associated disease, pelvic inflammatory
      disease and vaginal candidiasis is especially challenging in women with HIV
      infection. A positive status for the virus does not appear to affect pregnancy
      outcome. Each year, up to 2,000 infants are born infected with HIV. Transmission
      can occur by transplacental or intrapartum spread or through breast milk. Since
      1994, prophylaxis with zidovudine has been shown to be an effective method of
      limiting transmission to infants. It is important to offer all pregnant women a
      test for HIV, with counseling provided both before and after the test, even if
      testing does not become mandatory under the law.

PMID- 8857779
TI  - Diagnosis and management of fecal incontinence in elderly patients.
AB  - Fecal incontinence is a physically and psychologically disabling condition that
      affects millions of Americans, especially those over the age of 65 years. The
      pathophysiology is often multifactorial, with decreased anorectal sensation,
      reduced rectal compliance. anal sphincter dysfunction, altered stool consistency
      and immobility playing significant roles. A detailed history and a thorough
      physical examination are always necessary in patients with fecal incontinence and
      physiologic tests, including anorectal manometry, cinedefecography and
      electromyography, may be required for proper diagnosis and treatment. In most
      patients fecal incontinence is initially treated with conservative measures, such
      as biofeedback training or alteration of the stool consistency (if appropriate).
      If conservative management fails, surgical intervention, such as sphincteroplasty
      or gracilis muscle transposition, may be considered.

PMID- 8857780
TI  - Differentiating wide complex tachycardias.
AB  - Wide complex tachycardias are cardiac rhythm disorders with three or more
      consecutive beats, rates exceeding 100 beats per minute and a QRS duration of 120
      msec (0.12 second) or greater. The width of the QRS complex should be verified in
      a number of leads, since the QRS complex often appears mistakenly narrower (i.e.,
      a QRS duration of less than 120 msec) in one or two of the 12 leads. Most wide
      complex tachycardias are ventricular tachycardia, and they are managed with
      antiarrhythmic drugs and correction of serum potassium and magnesium levels.
      Electrical cardioversion/defibrillation may be used in patients with serious
      cardiac compromise. Supraventricular tachycardias occur with or without
      ventricular conduction abnormalities. The management of supraventricular
      tachycardia requires careful evaluation for aberrant ventricular conduction or
      preexcitation. The cause of a wide complex tachycardia must be identified,
      because certain therapies can result in potentially fatal arrhythmias. If the
      cause cannot be determined, a test dose of intravenous adenosine can be used.
      Another approach is intravenous administration of procainamide and a beta
      adrenergic blocker.

PMID- 8857781
TI  - Transient synovitis of the hip in children.
AB  - Transient synovitis is the most common cause of acute hip pain in children three
      to 10 years of age. Children with this condition typically present with hip pain
      for one to three days, accompanied by limping or the refusal to bear weight.
      Transient synovitis has an uncertain etiology and remains a diagnosis of
      exclusion. First, septic arthritis must be ruled out, since femoral head
      destruction, degenerative arthritis and permanent deformity can occur if septic
      arthritis is not treated promptly. Septic arthritis should be suspected in a
      patient with severe pain or spasm on hip movement or palpation, a temperature
      higher than 37.5 degrees C (99.5 degrees F) and an erythrocyte sedimentation rate
      of 20 mm per hour or greater. Hip aspiration is the diagnostic procedure of
      choice if septic arthritis is suspected. Treatment of transient synovitis
      consists of bed rest and nonsteroidal anti-inflammatory drugs, with regular
      temperature checks to exclude the onset of fever. If significant pain and limping
      persist seven to 10 days after the initial presentation, the patient should be
      reevaluated.

PMID- 8857782
TI  - Treatment of chronic hepatitis B and hepatitis C with interferon alfa-2b.
AB  - Chronic viral hepatitis B and C are problems of immense proportions. Interferon
      alfa-2b is the only agent currently approved by the U.S. Food and Drug
      Administration for the treatment of chronic hepatitis B and C. Initial enthusiasm
      for this therapy has waned with the realization that response rates are low and
      relapses are common. Recent studies, however, provide evidence of improved
      response rates with higher doses of interferon alfa-2b and the use of this agent
      in combination with iron reduction therapy consisting of repeated phlebotomies.
      Predictors of an increased likelihood of response to interferon alfa-2b therapy
      have also been identified, and their use may improve the cost-benefit ratio for
      this treatment.

PMID- 8857783
TI  - Evaluation and diagnosis of ankle injuries.
AB  - The evaluation of ankle injuries is a common challenge for family physicians.
      Diagnosis is made by using knowledge of the anatomy and function of the ankle
      joint to aid in taking an adequate history and performing an appropriate physical
      examination. The patient should be questioned about the mechanism of injury,
      previous injury, disability, treatment and pain. The ankle should be evaluated
      for ecchymosis, swelling, areas of tenderness and laxity. These measures help to
      determine what, if any, additional diagnostic procedures may be needed. Most
      ankle sprains are lateral, affecting the anterior talofibular, calcaneofibular
      and posterior talofibular ligaments. Other injuries include medial ankle sprains
      affecting the deltoid ligament, trauma to the Achilles and peroneal tendons,
      tarsal tunnel syndrome, fractures, syndesmotic sprains, synovial impingement and
      chronic instability. Criteria for radiographic evaluation include inability to
      bear weight initially or when examined, and tenderness over the medial or lateral
      malleolus. Accurate diagnosis is critical for appropriate treatment and
      minimizing functional disability.

PMID- 8857784
TI  - Surgical treatment of Parkinson's disease.
AB  - Improved understanding of the pathophysiologic mechanisms underlying parkinsonian
      signs and symptoms, as well as refinement of methods and techniques in
      neurosurgery, neuroradiology and neurophysiology, have stimulated the current
      interest in and expanded the role of surgical treatment of Parkinson's disease.
      Pallidotomy and thalamotomy are the stereotactic procedures most commonly
      performed in patients who fall to obtain satisfactory relief of their symptoms
      despite optimal medical therapy. Small lesions disrupt the abnormal activity of
      basal ganglia circuitry. Other options currently being studied include chronic
      high-frequency stimulation and transplantation of fetal mesencephalic tissue.
      Chronic thalamic stimulation, involving permanent implantation of a deep brain
      electrode and a pulse generator, effectively controls contralateral tremor. Fetal
      nigral transplantation, which is still an experimental procedure, has the
      potential of restoring lost nigrostriatal pathway. The choice of treatment
      depends on the severity of the symptoms and their response, or lack of response,
      to pharmacologic therapy. With appropriate selection criteria, functional and
      symptomatic improvement can be achieved in most patients with Parkinson's disease
      who are treated with neurosurgical procedures. The long-term effects of these
      treatments, however, await the results of longitudinal studies.

PMID- 8857785
TI  - Use of the rapid streptococcus test in extrapharyngeal sites.
AB  - The rapid "strep" test is established as a valuable tool for the management of
      pharyngitis. Because of the recent increase in reports of serious, rapidly
      progressive streptococcal soft tissue infections, the test can also be useful in
      determining early management of skin infections. Patients with positive results
      can be treated immediately with specific therapy, usually with an excellent
      outcome. As an illustration, use of this technique in 15 patients is described.

PMID- 8857786
TI  - Three-phase bone scan in osteomyelitis and other musculoskeletal disorders.
AB  - The three-phase bone scan is very sensitive and is the study of choice in the
      evaluation of patients with suspected osteomyelitis and normal radiographs. If
      the underlying bone pathology, such as a healing fracture or degenerative
      disease, is detected on radiographs of the bone, the indium-111-labeled
      autologous leukocyte scan is the most cost-effective second study. When fracture
      of the long bones is clinically suspected but radiographs are normal and a delay
      in definitive diagnosis is acceptable, it is practical and economical to take
      follow-up films in 10 to 14 days. In cases requiring prompt diagnosis or when
      follow-up radiographic films are not diagnostic, the three-phase bone scan is the
      most cost-effective study. The three-phase bone scan is also used in the
      evaluation of occupational and sports injuries, including shin splints, stress
      and occult fractures, enthesiopathies and reflex sympathetic dystrophy.

PMID- 8857787
TI  - Environmental control of dust mite allergens.
AB  - House dust mites are a major cause of allergic airway disease. Ninety percent of
      patients with asthma show dermal reactivity to house dust mite allergens. Control
      of these arachnids in the home environment can reduce the morbidity from atopic
      diseases and may moderate or even prevent the development of clinical disease in
      atopic individuals.

PMID- 8857788
TI  - Managing acute and chronic urinary incontinence. AHCPR Urinary Incontinence in
      Adults Guideline Update Panel.

PMID- 8857789
TI  - Erectile dysfunction.
AB  - Erectile dysfunction affects millions of men in this country. Impairment of
      neurologic, hormonal and vascular function can inhibit the corporal smooth muscle
      relaxation necessary for erectile function. Physicians should employ a diagnostic
      work-up that proceeds from a history and physical examination to laboratory
      studies and physiologic testing. Treatment, which should be prescribed with
      constant patient input, is successful in a high percentage of cases. For erectile
      dysfunction with psychogenic or hormonal etiologies, treatments target the
      specific underlying problem. For dysfunction caused by nonspecific vascular and
      neurogenic problems, useful treatments include medication, vacuum devices,
      intracavernosal injections and penile implants.

PMID- 8857790
TI  - Topical antifungal agents: an update.
AB  - So many topical antifungal agents have been introduced that it has become very
      difficult to select the proper agent for a given infection. Nonspecific agents
      have been available for many years, and they are still effective in many
      situations. These agents include Whitfield's ointment, Castellani paint, gentian
      violet, potassium permanganate, undecylenic acid and selenium sulfide. Specific
      antifungal agents include, among others, the polyenes (nystatin, amphotericin B),
      the imidazoles (metronidazole, clotrimazole) and the allylamines (terbinafine,
      naftifine). Although the choice of an antifungal agent should be based on an
      accurate diagnosis, many clinicians believe that topical miconazole is a
      relatively effective agent for the treatment of most mycotic infections.
      Terbinafine and other newer drugs have primary fungicidal effects. Compared with
      older antifungal agents, these newer drugs can be used in lower concentrations
      and shorter therapeutic courses. Studies are needed to evaluate the clinical
      efficacies and cost advantages of both newer and traditional agents.

PMID- 8857796
TI  - CDC issues recommendations for the prevention of perinatal group B streptococcal
      disease.

PMID- 8857797
TI  - ACOG releases a report on chronic pelvic pain. American College of Obstetricians
      and Gynecologists.

PMID- 8857798
TI  - American Academy of Pediatrics develops guidelines for acute gastroenteritis in
      young children.

PMID- 8857799
TI  - FDA approval of nevirapine for HIV.

PMID- 8857800
TI  - Acute hypoglycemia masquerading as head trauma: a report of four cases.
AB  - Hypoglycemia, a commonly encountered metabolic emergency, is most often easily
      diagnosed and rapidly treated with satisfactory patient outcome. If not
      recognized and treated promptly, hypoglycemia may cause irreversible central
      nervous system injury; it rarely results in death. The classic presentation of
      hypoglycemia, a patient with diabetes mellitus on medical therapy (Insulin or
      oral hypoglycemic agents) who presents with an altered sensorium, is frequently
      seen in the emergency department (ED). Less often, patients with this metabolic
      emergency present to the ED in a manner suggestive of a situation other than
      hypoglycemia. Patients may present with seizure activity or focal neurological
      deficits, leading the physician to treat a primary neurological syndrome and not
      immediately recognize the primary cause of the problem. Alternatively, patients
      with hypoglycemia will present to the ED with an altered mental status after a
      traumatic event. The physician may again assume that the alteration in
      consciousness has resulted from a head injury and not a metabolic disorder. Four
      cases are presented in which the medical history of the event (i.e., trauma)
      suggested head injury as an explanation of the presentation when, in fact,
      hypoglycemia was responsible for the altered sensorium. The diagnosis of
      hypoglycemia is easily made with the performance of a bedside screening test
      which can be subsequently confirmed by laboratory blood analysis. It is
      imperative that emergency physicians consider hypoglycemia in all patients with
      any mental status abnormality, focal neurological deficit, or seizure activity,
      even when the findings seem to be explained initially by other etiologies.

PMID- 8857801
TI  - Interaction between the trauma team and families: lack of timely communication.
AB  - Families of critically ill patients desire early information regarding the
      condition of their relative. The purpose of this study was to determine how long
      family members waited before someone from the trauma team met with them to
      discuss the condition of their relative. This was a prospective, single-blinded
      study of a convenience sample of 63 trauma patients conducted at a trauma center.
      Observers recorded the time of arrival of the patient, time of family arrival,
      and the time the family was first contacted by the trauma team. Families arrived
      38 +/- 35 minutes after the patient. The mean time families waited before contact
      with the trauma team was 37 +/- 34 minutes. This study shows that the trauma team
      is often slow in communicating with the family of the victim. One member of the
      caregiving team should be designated to advise the family on the condition of the
      patient as soon as possible.

PMID- 8857802
TI  - Simultaneous uvulitis and epiglottitis without fever or leukocytosis.
AB  - A case is presented of simultaneous uvulitis and epiglottitis in an afebrile
      patient without elevation in the white blood cell count. This case is reported to
      illustrate the need for a high index of suspicion for the rare association of
      uvulitis and epiglottitis.

PMID- 8857803
TI  - Vomiting, ataxia, and altered mental status in an adolescent: late-onset
      ornithine transcarbamylase deficiency.
AB  - A case of a 13-year-old boy with protracted vomiting, ataxia, and altered mental
      status, ultimately diagnosed with late-onset ornithine transcarbamylase (OTC)
      deficiency, is presented. OTC deficiency is the most common urea cycle defect and
      typically is diagnosed in male infants with irritability, poor feeding, vomiting,
      lethargy, and often death caused by the effects of hyperammonemia. Late-onset OTC
      deficiency has been described in patients of all ages. The presenting symptoms in
      these patients vary but the most common are vomiting and lethargy. The
      pathophysiology, clinical features, differential diagnosis, and treatment of this
      disorder are discussed. Because of the risks of serious consequences, early
      detection and treatment of OTC deficiency and hyperammonemic episodes are
      mandatory. Emergency physicians caring for children and adults need to be aware
      of the spectrum of clinical presentations of OTC deficiency, including late-onset
      disease.

PMID- 8857804
TI  - Deep vein thrombosis, pulmonary embolism, and the white clot syndrome.
AB  - Thromboembolic events such as deep vein thrombosis (DVT) and pulmonary embolism
      (PE) are very uncommon in the pediatric age group; even more rare is the white
      clot syndrome. We present the case of a 13-year-old girl who presented with no
      known risk factors for thromboembolic disease or cardiopulmonary complaints, yet
      was found to have extensive lower extremity DVT and PE. This patient also
      suffered the rare but potentially devastating complication of heparin therapy
      referred to as the white clot syndrome, resulting in amputation of the lower
      extremity. Greater awareness of both thromboembolic disease in children and the
      white clot syndrome may lessen the morbidity and mortality associated with these
      entities.

PMID- 8857805
TI  - Enhancing the value of journal club: use of a structured review instrument.
AB  - A study was undertaken to determine if use of a structured review instrument
      (SRI) increased the perceived overall satisfaction with a journal club in a group
      of emergency medicine residents. Before and 6 months after the introduction of a
      structured checklist format for article review, a 5-point Likert scale (1 =
      worst, 5 = best) was used to assess residents' satisfaction with the journal
      club, as well as the following subsidiary outcome parameters resident and leader
      workload, educational value in interpreting the medical literature, and
      application of the information to clinical practice. Additional measured outcome
      variables included resident attendance and number of articles read per attendee.
      Continuous and categorical data were compared using the Wilcoxon Rank Sum test
      and Fisher's exact test, respectively. Following introduction of the SRI,
      residents were more satisfied with the journal club (3.8 v 3.2, P < .05). There
      was no change in resident attendance (92% v 71%, P = .65), total articles read
      (75% v 70%, P = .33), or perceived workload (3.3 v 3.1; P = .3). The use of a SRI
      was found to increase resident satisfaction and improve the perceived educational
      value of a journal club without increasing residents' workload or decreasing
      attendance.

PMID- 8857806
TI  - Video assessment of trauma response: adherence to ATLS protocols.
AB  - A novel strategy using videotape recordings of initial trauma resuscitations was
      incorporated into the quality assurance program at a level 1 trauma center.
      Described are the process of taping the resuscitations, the multidisciplinary
      nature of the resuscitation team, the security measures taken to assure patient
      confidentiality, and the review process involved. The videotape review process
      was incorporated into a multidisciplinary educational trauma conference. The
      videotapes were used to evaluate the adherence to Advanced Trauma Life Support
      (ATLS) resuscitation protocols. Resident performance in six aspects of the ATLS
      resuscitation process were specifically highlighted on each videotape and graded
      for adherence to preestablished standards. The videotape process allowed an
      unblased, indisputable accurate documentation of the sequential application of
      the protocols of evaluation and resuscitation espoused in the ATLS course. We
      found 23% overall deviation from ATLS resuscitation principles, with at least one
      aspect of the resuscitation deviating from expected ATLS performance in 64% of
      the patients. In addition to documenting adherence to ATLS principles, this study
      illustrated the impact of the videotape review process on the education of eight
      senior residents in surgery.

PMID- 8857807
TI  - Acute myocardial infarction in a previously healthy adolescent.
AB  - Acute myocardial infarction in an adolescent is rare, with most episodes
      occurring in individuals with preexisting traumatic or medical conditions. Acute
      myocardial infarction in a previously healthy adolescent is an even more rare
      event. This report details such an event and briefly reviews the recent medical
      literature.

PMID- 8857808
TI  - An association between snowfall and ED presentation of cardiac arrest.
AB  - Studies from several cities have reported increased cardiovascular mortality
      associated with snowfall; whether this weather also results in increased
      emergency department (ED) presentation of cardiac arrests is not known. A
      retrospective review was conducted of cardiac arrest patients presenting to a New
      England ED during the months of October through May, from 1991 to 1994. Comparing
      daily frequency of cardiac arrest patients with climactic data, a 27% increase
      was observed in the frequency of cardiac arrest presentation to the ED on days
      with snowfall (P = .0004). ED physicians and staff should anticipate an increased
      frequency of cardiac arrest patients on days with snowfall.

PMID- 8857809
TI  - Rhabdomyolysis: a rare adverse effect of diphenhydramine overdose.
AB  - Drug- and toxin-induced rhabdomyolysis is a nonspecific clinical syndrome
      resulting from the release of skeletal muscle cell contents into the plasma and
      urine. Antihistamine drugs are the active ingredients in a number of over-the
      counter preparations and are frequently ingested in suicide attempts. We report
      rhabdomyolysis as a rare adverse effect of diphenhydramine toxicity in a 29-year
      old man who ingested an unknown quantity of an over-the-counter sleep preparation
      in a suicide attempt. The patient had documented toxic concentration of
      diphenhydramine in his cerebrospinal fluid and no history of seizures, coma, or
      hypothermia. A high index of suspicion and an evaluation for rhabdomyolysis is
      warranted in antihistamine toxicity.

PMID- 8857810
TI  - Sulfonamide-induced iritis.
AB  - Anterior uveitis is a relatively rare adverse drug reaction when the prescription
      rate of sulfonamides is considered. Current medications should be included in the
      differential diagnosis of patients who present with uveitis, because
      discontinuation of the offending agent is mandatory to resolution of the problem.
      Lack of recognition and failure to discontinue the medication will increase the
      patient's risk of ocular injury.

PMID- 8857811
TI  - Respiratory arrest after intramuscular ketamine in a 2-year-old child.

PMID- 8857812
TI  - Extra-articular calcium pyrophosphate deposition disease presenting as neck pain
      and fever.

PMID- 8857813
TI  - A portable quantitative capnometer in test.
AB  - A new hand-held quantitative capnometer (BCI Capnocheck) was tested in the animal
      lab setting. The end-tidal CO2 values, as measured with this device, showed good
      agreement with arterial (Paco2) values. This device seems suited for quantitative
      capnometry in the prehospital setting. It must be noted, however, that this
      device has no alarms.

PMID- 8857814
TI  - Dermatologic problems encountered in the emergency department.

PMID- 8857815
TI  - Resuscitation after nifedipine overdose exclusively with intravenous calcium
      chloride.

PMID- 8857816
TI  - Acute esophageal food impaction treated by water-soluble contrast esophagography
      with maneuvers.
AB  - This report describes a case of acute esophageal food impaction in the lower
      esophagus treated by proper physical motions during esophagography using water
      soluble contrast medium (WSCM). WSCM was used to avoid the complication from
      unexpected perforation during the examination. Relief of esophageal obstruction
      may be accomplished by asking the patient to jump up and down on the ground.
      Esophagography using WSCM combined with appropriate physical motions may be
      helpful in treating patients suffering from acute esophageal food impaction.

PMID- 8857817
TI  - Treatment of theophylline overdose.

PMID- 8857818
TI  - First aid and transportation of burned patients during mass disasters.
AB  - Twenty-eight mass burn disasters in Bulgaria with 381 injuries in the last 27
      years (1968-1994) were reviewed. Mass burn disasters were classified as follows:
      industrial accidents, 23, with 273 injured and 103 dead; traffic accidents, 2,
      with 97 injured and 30 dead; domestic accidents, 2, with 11 injured and 6 dead.
      Organization of first aid at the disaster site and in the regional hospitals is
      described, as well as the time of transport of the patients to major hospitals
      near the site of the accident. As a priority, the injured were transported early
      to the biggest center for burns and plastic surgery in the capital.

PMID- 8857819
TI  - Vasectomy and prostate cancer: a case-control study in a health maintenance
      organization.
AB  - A case-control study was conducted within Group Health Cooperative of Puget Sound
      to evaluate the relation between prior vasectomy and the risk of prostate cancer.
      Cases consisted of 175 men newly diagnosed with histologically confirmed prostate
      cancer during 1989-1991. A total of 258 controls, matched to cases on birth year
      and membership status, were randomly selected from the general membership of the
      plan. Information was collected from mailed questionnaires and medical records on
      medical history, including prior vasectomy, anthropometric measures, family
      history of prostate cancer, personal habits, and medical care utilization, and
      demographic factors. Conditional logistic regression analyses showed that the
      odds ratio for prostate cancer associated with vasectomy was 0.86 (95% confidence
      interval 0.57-1.32) after adjustment for confounders. The odds ratio estimate did
      not differ substantially by age at vasectomy or time since vasectomy. However,
      the odds ratio estimate for prostate cancer associated with vasectomy tended to
      be increased among men who had a father or brother with prostate cancer.
      Nevertheless, the increased risk may be related to detection bias or differential
      participation rates due to both vasectomy status and a family history of prostate
      cancer. These results suggest no overall association between vasectomy and
      prostate cancer.

PMID- 8857820
TI  - Oncogene-related serum proteins and cancer risk: a nested case-control study.
AB  - Proto-oncogenes are genes coding for factors involved in cellular growth,
      reproduction, and differentiation. Cancer results through mutations of proto
      oncogenes or through other mechanisms involving the products of proto-oncogenes.
      This study asks whether serum proteins immunologically related to the products of
      proto-oncogenes distinguish older men and women who manifest a new cancer during
      a 2-year follow-up. The authors conducted a nested case-control study that
      involved 248 men and women selected from a larger group of older (age > or = 65
      years) healthy volunteers in a randomized clinical trial of preventive clinical
      services. Study subjects included 37 with a fatal cancer, 59 non-fatal breast,
      prostate, colon, or lung cancer, 58 hospitalized with at least one discharge
      diagnosis that coded to benign neoplasia (International Classification of
      Diseases, 9th Revision codes 210-239), and 94 randomly selected controls. Using
      seven monoclonal antibodies prepared against ras, erb-B, FES, myb, and SIS
      polypeptide sequences, immunoblots detected 17 proteins in serum collected from
      subjects before the clinical recognition of cancer. Five oncogene-related serum
      proteins appeared to distinguish older persons who manifested fatal (but not non
      fatal) cancer over a brief (2-year) follow-up. Older persons hospitalized with
      benign neoplasia also had higher levels of these serum proteins. Relative to the
      94 control subjects, a 52,000 dalton SIS-related protein (odd ratio (OR) = 5.9,
      95% confidence interval (CI) 1.4-24.9) and a 35,000 dalton k-ras-related protein
      (OR = 11.3, 95% CI 1.2-104) were particularly common in serum from the 37
      subjects who manifested a fatal cancer.

PMID- 8857821
TI  - Benign thyroid tumors: general risk factors and their effects on radiation risk
      estimation.
AB  - The authors examined risk factors for benign thyroid nodules and their influence
      on radiation effects among 544 subjects who were exposed to childhood radiation
      treatment for benign head and neck conditions at a Chicago, Illinois hospital
      during 1939-1962. In follow-up through 1991, benign thyroid nodules were
      diagnosed in 131 patients. The risk of benign nodules was elevated in women
      (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.6-3.2), Jews (RR = 1.7,
      95% CI 1.2-2.5), college graduates (RR = 1.8, 95% CI 1.2-2.8), and subjects whose
      mother had cancer (RR = 1.7, 95% CI 1.2-2.5). There were increasing trends for
      risk with increasing body mass index in women and decreasing height in men. Risk
      was increased for women who never married (RR = 3.7, 95% CI 1.6-7.3) or who never
      had a full-term pregnancy (RR = 2.0, 95% CI 1.1-3.3). A significant radiation
      dose-response relationship was observed that was not modified by sex, education,
      Jewish religion, or reproductive factors. The data suggest that there are
      genetic, life-style (including ascertainment), and hormonal factors associated
      with the development of benign thyroid nodules.

PMID- 8857822
TI  - Longitudinal relation between smoking and white blood cells.
AB  - Higher white blood cell counts in smokers compared with nonsmokers have been well
      documented, but the longitudinal relation between changes in smoking and changes
      in white blood cells has not been well described. Since 1984, data have been
      collected semiannually by the Multicenter AIDS Cohort Study (MACS), a four-center
      prospective cohort study of acquired immunodeficiency syndrome (AIDS) in
      homosexual men. The study population includes 2,435 participants who were human
      immunodeficiency virus (HIV) seronegative as of September 1994 and who
      contributed 20,918 person-visits for this analysis. For individuals who modified
      their smoking behavior, changes in white blood cell counts occurred primarily
      during the first 6 months following changes in the amount of cigarettes smoked.
      Among former smokers who resumed smoking, the extent of the increase in white
      blood cell count depended on the number of cigarettes smoked. Specifically,
      increases of 241, 340, and 740 cells/microliter were observed for smokers who
      resumed smoking < 1, 1 to < 2, and > or = 2 packs/day, respectively. Conversely,
      smokers who quit smoking had a decrease of white blood cell count: -32, -629, and
      -1,122 cells/microliter for men who previously smoked < 1, 1 to < 2, and > or = 2
      packs/day, respectively. Long-term ex-smokers, however, still had higher white
      blood cell counts than did never smokers. There was a high within-individual
      correlation of white blood cell count in persons who reported a consistent level
      of smoking (i.e., average correlations between two white blood cell counts 6
      years apart were 0.51 for never smokers, 0.48 for ex-smokers, 0.56 for men who
      smoked < 1 pack/day, and 0.43 for men who smoked > or = 1 pack/day). These
      analyses indicate an acute effect of changes in smoking on changes in white blood
      cell count, a residual effect of having been a smoker, and high long-term
      tracking for white blood cell count.

PMID- 8857823
TI  - Femoral atherosclerosis in middle-aged subjects: association with cardiovascular
      risk factors and insulin resistance.
AB  - The aim of this 8-year follow-up study was to investigate the role of
      conventional cardiovascular risk factors as predictors for asymptomatic femoral
      atherosclerosis. The authors also evaluated the association of insulin resistance
      with atherosclerosis in a cross-sectional setting. Cardiovascular risk factors of
      118 subjects were studied at the baseline study in 1983-1985 in Kuopio, Finland.
      Femoral atherosclerosis, defined as a presence of plaques, was investigated by
      ultrasonography in the follow-up study in 1992-1993. In the univariate logistic
      regression analyses, age (p = 0.002), systolic and diastolic blood pressure (p =
      0.002 and p = 0.013, respectively), total cholesterol (p = 0.005), low density
      lipoprotein (LDL) cholesterol (p = 0.005), total triglycerides (p = 0.033), LDL
      triglycerides (p = 0.033), apolipoprotein B (p = 0.045), and fasting plasma
      glucose (p = 0.011) had a significant association with the presence of femoral
      plaques. Plasma insulin levels and insulin sensitivity index, determined in 87
      subjects by an intravenous glucose tolerance test and minimal model at the follow
      up study, were not associated with femoral plaques. The results demonstrate that
      atherogenic lipid and lipoprotein pattern and blood pressure are strongly
      associated with femoral atherosclerosis, whereas insulin sensitivity and
      hyperinsulinemia seem not to play such a significant role.

PMID- 8857824
TI  - Determinants of bone and blood lead levels among community-exposed middle-aged to
      elderly men. The normative aging study.
AB  - Levels of lead in bone serve as a dosimeter for cumulative exposure to lead;
      moreover, lead in bone may serve as an internal source of circulating lead many
      years after environmental exposure has ceased. The authors measured lead in blood
      and used a K-x-ray fluorescence instrument to measure lead in the tibia
      (cortical) and patella (trabecular) bones in a cross-sectional survey of 719
      middle-aged to elderly male participants in the Normative Aging Study who were
      without unusual occupational exposures to lead and who were healthy when enrolled
      in 1962-1965. Blood lead levels ranged from < 1 to 27.9 micrograms/dl, with a
      geometric mean of 5.7 micrograms/dl. Tibia and patella lead level ranges
      (geometric means) were < 1-51 (20.8) micrograms/g and 3-77 (29.8) micrograms/g,
      respectively. In backwards elimination multivariate regression models that
      considered age, race, education, retirement status, measures of both current and
      cumulative smoking, and alcohol consumption, the factors that remained
      significantly related to higher levels of both tibia and patella lead were higher
      age and measures of cumulative smoking, and lower levels of education. In the
      final model predicting blood lead that began with these same covariates and also
      included tibia and patella lead, the factor that accounted for the dominant
      portion of the variance in blood lead was patella lead. After adjustment for
      measurement error, a rise in patella lead from the median of the lowest to the
      median of the highest quintiles (13-56 micrograms/g) corresponded to a rise in
      blood lead of 4.3 micrograms/dl. The authors conclude that bone lead levels are
      substantial and comprise the major source of circulating lead in these men.

PMID- 8857825
TI  - Prevalence of dementia and its subtypes in the Japanese American population of
      King County, Washington state. The Kame Project.
AB  - Studies of Asian populations generally have reported prevalence rates for
      dementia similar to those of predominantly Caucasian populations, but relative
      prevalence rates of Alzheimer's disease and vascular dementia have differed.
      Between May 1, 1992 and May 1, 1994, the prevalence rates of dementia,
      Alzheimer's disease, and vascular dementia were examined in the Japanese American
      population aged over 65 years in King County, Washington State. A total of 3,045
      eligible individuals were identified in a census of persons who were of at least
      50% Japanese heritage. Of 1,985 persons who participated in the baseline
      examination, 382 individuals of 450 sampled from all cognitive performance strata
      received a diagnostic evaluation. A total of 107 cases with a Clinical Dementia
      Rating (CDR) of > or = 1 met criteria for dementia according to the Diagnostic
      and Statistical Manual, 3rd edition, revised (DSM-III-R); 58 of these cases were
      diagnosed with Alzheimer's disease and 24 with multi-infarct dementia. The
      estimated prevalence rate for all dementias was 6.3% (95% confidence interval 5.9
      6.8). Prevalence rates for dementia increased continuously with age and were 30%,
      50%, and 74% for participants aged 85-89, 90-94, and > or = 95 years,
      respectively; for Alzheimer's disease, prevalence rates were 14%, 36%, and 58%
      for these three age groups. Rates for Alzheimer's disease were generally higher
      among women; for multi-infarct dementia, rates for men and women were similar. In
      the institutional population, the prevalence rate was 66%, and in the community,
      2.9%. Persons with lower education had higher overall rates of dementia than
      those with higher education, but this tendency became weak and inconsistent when
      rates were age-stratified. The prevalence of dementia in this geographically
      defined population of Japanese Americans was somewhat higher than prevalence
      rates reported from Japan, and the distribution of dementia subtypes more closely
      resembled that found in Caucasian populations in North America and Europe than
      previously reported in Asian populations.

PMID- 8857826
TI  - Large declines in sexual risk behavior with noncommercial partners among
      heterosexual injection drug users in Amsterdam, 1989-1995.
AB  - Previous studies among injection drug users have reported small or nonexistent
      reductions in sexual risk behavior with noncommercial partners, and a large
      potential for further heterosexual spread of human immunodeficiency virus (HIV)
      is thought to be present. In the present study, a long-term follow-up and
      detailed data on sexual behavior were available. Trends were determined using
      data collected at 5,214 visits of 653 heterosexual injection drug users who
      participated in the Amsterdam Cohort Study in Amsterdam, the Netherlands between
      April 1989 and May 1995. Analysis accounted for repeated measurements of one
      individual and the effect of participation in the study itself. The authors
      observed a large reduction in sexual risk behavior with noncommercial partners
      that became apparent only after stratification of trends by knowledge of HIV
      serostatus. Sex with noncommercial partners and inconsistent condom use both
      decreased, especially among known HIV-positive individuals. Apart from nonrandom
      condom use, there also was nonrandom mixing (selective partner choice). Because
      this was like-with-like mixing, the risk for further sexual transmission of HIV
      is diminished. In future studies, more detailed information on sexual behavior,
      mixing, and knowledge of serostatus should be collected. HIV-epidemic modelers
      should incorporate nonrandom condom use and nonrandom mixing to improve
      forecasting.

PMID- 8857827
TI  - Misclassification model for person-time analysis of automated medical care
      databases.
AB  - A misclassification model is presented for the assessment of bias in rate ratios
      estimated by person-time analyses of automated medical care databases. The model
      allows for misclassification of events and person-time and applies to both
      differential and nondifferential errors. The focus is on medical care exposures
      that occur at discrete points in time (e.g., vaccinations) and on adverse events
      that are closely associated in time. Bias corrections for rate ratios and
      binomial tests of equality of event rates during exposed and unexposed person
      time are developed and illustrated. For nondifferential under- or over
      ascertainment of events, the observed rate ratio (r) is unbiased at the null
      hypothesis (true rate ratio R = 1), negatively biased when R > 1, and positively
      biased when R < 1 (i.e., biased toward the null). Differential under
      ascertainment of unexposed events and differential over-ascertainment of exposed
      events positively bias r when R = 1. Differential event sensitivities cause
      larger biases in rate ratios than differential false event rates. False positive
      exposures bias observed event rate ratios more than false negative exposures.
      Biases are small when event sensitivities are nondifferential and when less than
      10% of database exposures and events are false. The usefulness of the model for
      critical sensitivity analysis is illustrated by an example from a linked database
      study of childhood vaccine safety. Greater dissemination of data quality
      assessments, sensitivity analyses, and methods used to supplement automated
      databases are needed to further our understanding of the appropriate role of
      medical care databases in epidemiologic research.

PMID- 8857828
TI  - Natural history of leisure-time physical activity and its correlates:
      associations with mortality from all causes and cardiovascular disease over 28
      years.
AB  - The association between leisure-time physical activity and 28-year (1965-1993)
      risk of death from all causes and cardiovascular disease was studied in 6,131
      adults who participated in the Alameda County Study in Northern California.
      Because study participants were interviewed on a number of occasions, it was
      possible to include in the analyses information on changes over time in levels of
      leisure-time physical activity as well as changes in a wide variety of other risk
      factors. There were 47,616 person-years of observation for males (639 deaths from
      all causes and 321 from cardiovascular disease) and 57,666 person-years of
      observation for females (587 deaths from all causes and 388 from cardiovascular
      disease). In analyses in which only the baseline values of all covariates were
      included, a four-point increase on the leisure-time physical activity scale, the
      interquartile range, was associated with reduced risk of death from all causes
      (relative risk (RR) = 0.90, 95% confidence interval (CI) 0.83-0.99) and
      cardiovascular disease (RR = 0.85, 95% CI 0.75-0.97). When time-varying
      information on leisure-time physical activity and all other covariates was
      included, there was still a protective effect for all-cause and cardiovascular
      disease mortality (RR = 0.84, 95% CI 0.77-0.92 and RR = 0.81, 95% CI 0.71-0.93,
      respectively). The association between leisure-time physical activity and risk of
      death was not altered when information on variations over time in leisure-time
      physical activity and many determinants and consequences of physical activity
      were explicitly included in survival models.

PMID- 8857829
TI  - Re: "Long-term hormone replacement therapy and risk of breast cancer in
      postmenopausal women".

PMID- 8857830
TI  - Re: "Effects of caffeine consumption on delayed conception".

PMID- 8857831
TI  - Re: Effects of caffeine consumption on delayed conception.

PMID- 8857832
TI  - Re: Effects of caffeine consumption on delayed conception.

PMID- 8857833
TI  - Re: "Heterogeneity of hip fracture: age, race, sex, and geographic patterns of
      femoral neck and trochanteric fractures among the US elderly".

PMID- 8857834
TI  - Re: "Morton Levin (1904-1995): history in the making".

PMID- 8857835
TI  - Re: "Magnetic fields and cancer in children residing near Swedish high-voltage
      power lines".

PMID- 8857836
TI  - Alexander D. Langmuir--his impact on public health.

PMID- 8857837
TI  - Training field epidemiologists: Alexander D. Langmuir and the epidemic
      intelligence service.

PMID- 8857838
TI  - Implementing the concepts of William Farr: the contributions of Alexander D.
      Langmuir to Public Health Surveillance and Communications.

PMID- 8857839
TI  - Statistical methods in public health: the influence of Alexander D. Langmuir.

PMID- 8857840
TI  - Infectious Disease Epidemiology.

PMID- 8857841
TI  - Airborne disease: including chemical and biological warfare.

PMID- 8857842
TI  - Veterinary public health and Alexander D. Langmuir.

PMID- 8857843
TI  - Contributions of Alexander D. Langmuir to the epidemiologic study of population
      change and family planning.

PMID- 8857845
TI  - Passing the epidemiologic torch from Farr to the world. The legacy of Alexander
      D. Langmuir.

PMID- 8857844
TI  - Cancer, environmental health, and birth defects--examples of new directions in
      public health practice.

PMID- 8857846
TI  - Alexander Duncan Langmuir.

PMID- 8857847
TI  - Patient, hospital, and surgeon factors associated with breast conservation
      surgery. A statewide analysis in North Carolina.
AB  - OBJECTIVE: The objective of this study was to determine the trend of breast
      conservation surgery (BCS) in North Carolina over a 6-year period and to identify
      patient, hospital, and surgeon factors associated with the use of BCS. SUMMARY
      BACKGROUND DATA: Despite evidence that BCS is an appropriate method of treatment
      for early stage breast cancer, surgeons in the United States have been slow to
      adopt this treatment method. METHODS: Cases of primary breast cancer surgery in
      all 157 hospitals in the state from 1988 to 1993, inclusive (N = 20,760), were
      obtained from the State Medical Database Commission, Area Resource File, American
      Hospital Association and State Board of Medical Examiner's Databases. Multiple
      logistic regression was used to generate odds ratios (ORs) and 95% confidence
      intervals (CIs) to determine factors associated with BCS. RESULTS: The rate of
      BCS doubled from 7.3% in 1988 to 14.3% in 1993, with an overall rate of 10.2%
      (2117/ 20.760). Multiple logistic regression identified the following factors
      associated with BCS: patient age younger than 50 years of age (OR = 1.7, 95% CI =
      1.4, 2.1), patient age 50 to 69 years of age (OR = 1.2, 95% CI = 1.1, 1.4),
      private insurance (OR = 1.2, 95% CI = 1.0, 1.4), hospital bed size 401+(OR = 2.0,
      95% CI = 1.6, 2.5), bed size 101 to 400 (OR = 1.7, 95% CI = 1.3, 2.1), and
      surgeon graduation from medical school since 1981 (OR = 1.6, 95% CI = 1.2, 2.0).
      CONCLUSIONS: Rates of BCS in North Carolina are low. Least likely to have BCS
      were women older than 70 years of age, without private insurance, treated at
      small hospitals by older surgeons. To increase the use of BCS, widespread
      education of surgeons, other health care providers, policy makers, and the
      general public is warranted.

PMID- 8857848
TI  - Prenatal glucocorticoid therapy reverses pulmonary immaturity in congenital
      diaphragmatic hernia in fetal sheep.
AB  - OBJECTIVE: To assess the feasibility of conducting clinical trials of prenatal
      steroid therapy for congenital diaphragmatic hernia (CDH) in humans, the authors
      tested whether prenatal glucocorticoid, currently the standard treatment to
      minimize respiratory distress syndrome in premature infants, might improve the
      pulmonary immaturity in severe CDH in a large animal model. SUMMARY BACKGROUND
      DATA: The authors have used the nitrofen-induced rat model of CDH, which
      demonstrates immature lungs by biochemical, morphometric, and molecular biologic
      criteria. They also have shown that the lethally immature lungs of the full-term
      CDH rats can be improved by biochemical, morphometric, physiologic, and molecular
      criteria by treating the mothers with parenteral steroids at doses extrapolated
      from the current therapy used to accelerate lung development of premature human
      babies. METHODS: During a 3-year period in 88 fetal sheep, 1) left-sided
      diaphragmatic hernias were created surgically at varying gestational ages (day 78
      90; term = 142-145 days) and size to maximize severity (n = 45), 2) placement and
      design of indwelling fetal intravenous catheters were optimized (n = 13), and 3)
      timing and dosage of cortisol administration were determined (n = 17). As a
      result, diaphragmatic hernias were created on day 80, intravenous catheters were
      placed on day 120, and twice-daily intravenous cortisol injections (n = 8) or
      saline as the control (n = 5) were administered (days 133-135). Lambs were
      delivered on day 136 via cesarean section to avoid steroid-induced abortion;
      vascular access was obtained, and the fetuses were ventilated at standard
      settings. Physiologic data were collected, and lungs were harvested for
      biochemical and histologic analysis. RESULTS: Significant improvements were
      measured in postductal arterial oxygen pressure ([PaO2] 38 +/- 6 mmHg after
      cortisol therapy compared with 20 +/- 3 mmHg for saline controls; p = 0.002) and
      in dynamic compliance (0.42 +/- 0.05 mL/cm H2O vs. 0.29 +/- 0.01 mL/cm H2O; p =
      0.01). Lung glycogen levels in the right lung of the cortisol group were
      significantly better than controls (4.6 +/- 0.3 mg/g lung vs. 6.8 +/- 0.4 mg/g; p
      = 0.002), as were protein/DNA levels (8.3 +/- 0.9 mg/mg vs. 14.5 +/- mg/mg; p <
      0.05). Striking morphologic maturation of airway architecture was observed in the
      treated lungs. CONCLUSIONS: Prenatal glucocorticoids correct the pulmonary
      immaturity of fetal sheep with CDH by physiologic, biochemical, and histologic
      criteria. These data, combined with previous small animal studies, have prompted
      the authors to initiate a prospective phase I/II clinical trial to examine the
      efficacy of prenatal glucocorticoids to improve the maturation of hypoplastic
      lungs associated with CDH.

PMID- 8857849
TI  - Equivalent success of simultaneous pancreas kidney and solitary pancreas
      transplantation. A prospective trial of tacrolimus immunosuppression with
      percutaneous biopsy.
AB  - OBJECTIVE: This study was designed to evaluate the results of solitary pancreas
      transplantation in a protocol that uses the new immunosuppressant tacrolimus (FK)
      and liberally applies ultrasound-guided percutaneous pancreas biopsy to diagnose
      rejection. SUMMARY BACKGROUND DATA: Pancreas graft survival in patients who
      simultaneously receive a kidney transplant (SPK) historically has been 75% to 90%
      at 1 year, approaching that of cadaveric kidney transplantations. In sharp
      contrast, graft survival rates in patients who receive a pancreas atone (PA) have
      remained static over the past decade, with approximately 50% functional at 1
      year. It was hypothesized that the results of PA transplantations would improve
      with newer maintenance immunosuppressants and biopsy techniques. METHODS: Twenty
      seven PA recipients prospectively were treated with FK-based immunosuppression
      (PA-FK). Percutaneous biopsy was performed for hyperamylasemia, hyperlipasemia,
      hypoamylasuria, or unexplained fever. One year pancreas graft survival in these
      patients was compared to 15 cyclosporine treated PA cases (PA-CsA) and 113 SPK
      recipients. RESULTS: The 1-year pancreas graft survival rate of 90.1% in
      technically successful PA-FK patients was significantly better than the 53.4%
      rate in PA-CsA recipients (p = 0.002) and no different than the 87.4% rate in SPK
      recipients. The only graft lost to acute rejection in the PA-FK group was because
      of acknowledged patient noncompliance. Percutaneous biopsy substantially improved
      the diagnostic certainty in cases of suspected rejection and was associated with
      a low complication rate (3/178 = 1.5%). CONCLUSIONS: Modern immunosuppression and
      biopsy techniques have improved the success of solitary pancreas transplantations
      to the point where outcome is now equivalent to that of SPKs.

PMID- 8857850
TI  - "Keyhole" coronary artery bypass surgery.
AB  - OBJECTIVE: The objective of this study was to identify the utility of "keyhole"
      thoracotomy approaches to single vessel coronary artery bypass surgery. SUMMARY
      BACKGROUND DATA: Although minimally invasive surgery is efficacious in a wide
      variety of surgical disciplines, it has been slow to emerge in cardiac surgery.
      Among 49 selected patients, the authors have used a left anterior keyhole
      thoracotomy (6 cm in length) combined with complete dissection of the eternal
      mammary artery (IMA) pedicle under thoracoscopic guidance or directly through the
      keyhole incision to accomplish IMA coronary artery bypass grafting (CABG) to the
      left anterior descending (LAD) coronary artery circulation or to the right
      coronary artery (RCA). METHODS: Keyhole CABG was accomplished in 46 of 49
      patients in which this approach was attempted. All patients had significant (>
      70%) obstruction of a dominant coronary artery that had failed or that was
      inappropriate for endovascular catheter treatment (percutaneous transluminal
      coronary angioplasty or stenting). Forty-four of the 49 patients had proximal LAD
      and 5 had proximal RCA stenoses. The mean age of the patients (35 men and 14
      women) was 61 years, and their median New York Heart Association anginal class
      was III. The mean left ventricular ejection fraction was 42%. Femoral
      cardiopulmonary bypass support was used in 9 (19%) of 46 patients successfully
      managed with the keyhole procedure. Short-acting beta-blockade was used in the
      majority of patients (38 of 46) to reduce heart rate and the vigor of cardiac
      contraction. RESULTS: As 49 patients have survived operation, which averaged 248
      minutes in duration. Median, postoperative endotracheal intubation time for
      keyhole patients was 6 hours with 25 of 46 patients being extubated before
      leaving the operating room. The median hospital stay was 4.3 days. Conversion to
      sternotomy was required in three patients to accomplish bypass because of
      inadequate internal mammary conduits or acute cardiovascular decompensation
      during an attempted off-bypass keyhole procedure Postoperative complications were
      limited to respiratory difficulty in three patients and the development of a deep
      wound infection in one patient. Nine (19%) of 46 patients received postoperative
      transfusion. There have been no intraoperative or postoperative infarctions, and
      angina has been controlled in all but one patient who subsequently had an IMA-RCA
      anastomotic stenosis managed successfully with percutaneous transluminal coronary
      angioplasty. CONCLUSIONS: These early results with keyhole CABG are encouraging.
      As experience broadens, keyhole CABG may become a reasonable alternative to
      repeated endovascular interventions or sternotomy approaches to recalcitrant
      single-vessel coronary arterial disease involving the proximal LAD or RCA.

PMID- 8857851
TI  - Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors.
AB  - OBJECTIVE: The objective of this article is to introduce a simple method for
      classifying cholangiocarcinomas and to apply this system to analyze a large
      number of patients from a single institution. SUMMARY BACKGROUND DATA: For the
      past 2 decades, most western reports on cholangiocarcinoma have separated
      intrahepatic from extrahepatic tumors and have subclassified this latter group
      into proximal, middle, and distal subgroups. However, "middle" lesions are
      uncommon and are managed most often either with hilar resection or with
      pancreatoduodenectomy. The spectrum of cholangiocarcinoma, therefore, is best
      classified into three broad groups: 1) intrahepatic, 2) perihilar, and 3) distal
      tumors. These categories correlate with anatomic distribution and imply preferred
      treatment. METHODS: The records of all patients with histologically confirmed
      cholangiocarcinoma who underwent surgical exploration at The Johns Hopkins
      Hospital over a 23-year period were reviewed. RESULTS: Of 294 patients with
      cholangiocarcinoma, 18 (6%) had intrahepatic, 196 (67%) had perihilar, and 80
      (27%) had distal tumors. Age, gender, race, and associated diseases were similar
      among the three groups. Patients with intrahepatic tumors, by definition, were
      less likely (p < 0.01) to be jaundiced and more likely (p < 0.05) to present with
      abdominal pain. The resectability rate increased with a more distal location (50%
      vs. 56% vs. 91%), and resection improved survival at each site. Five-year
      survival rates for resected intrahepatic, perihilar, and distal tumors were 44%,
      11%, and 28%, and median survival rates were 26, 19, and 22 months, respectively.
      Postoperative radiation therapy did not improve survival. In a multivariate
      analysis resection (p < 0.001. hazard ratio 2.80), negative microscopic margins
      (p < 0.01, hazard ratio 1.79), preoperative serum albumin (p < 0.04, hazard ratio
      0.82), and postoperative sepsis (p < 0.001, hard ratio 0.27) were the best
      predictors of outcome. CONCLUSIONS: Cholangiocarcinoma is best classified into
      three broad categories. Resection remains the primary treatment, whereas
      postoperative adjuvant radiation has no influence on survival. Therefore, new
      agents or strategies to deliver adjuvant therapy are needed to improve survival.

PMID- 8857852
TI  - A sarcoma-derived protein regulates hepatocyte metabolism via autocrine
      production of tumor necrosis factor-alpha.
AB  - OBJECTIVE: The effects of conditioned media from the methylcholanthrene (MCA)
      fibrosarcoma on hepatocyte albumin production and amino acid transport were
      studied. The authors characterized a factor responsible for the observed effects
      and investigated the role of tumor necrosis factor-alpha (TNF-alpha) in these
      events. SUMMARY BACKGROUND DATA: Cancer cachexia is mediated in part by TNF
      alpha. However, few tumors secrete TNF-alpha, implicating host production of this
      cytokine in response to as yet uncharacterized tumor-derived factors. Autocrine
      production of TNF-alpha recently has been described as a potent mechanism for
      orchestrating hepatic metabolism. METHODS: Conditioned media from the MCA
      fibrosarcoma was incubated with isolated primary rat hepatocytes. Albumin
      production and TNF-alpha production by hepatocytes was measured by enzyme-linked
      immunosorbent assay and amino acid transport assayed by tritium (3H)-labeled
      amino acid uptake. Dialysis membranes ranging from 3 kD to 100 kD were used to
      determine the size of the factor/factors responsible for the observed effects.
      RESULTS: Conditioned media from the MCA fibrosarcoma contained no TNF-alpha,
      whereas treatment of primary rat hepatocytes with the conditioned media resulted
      in a 53-fold increase in TNF-alpha production by hepatocytes compared with
      control. Treatment of hepatocytes with MCA fibrosarcoma-conditioned media
      resulted in decreases in hepatic albumin production of 46%, 61%, and 42% over 3
      days of treatment, and these effects were reversible by the addition of antibody
      to TNF-alpha. Treatment of hepatocytes with MCA fibrosarcoma conditioned media
      resulted in increases in hepatocyte amino acid transport via inductions of System
      N (1.87 fold) and System A (1.93 fold). These effects were partially abrogated by
      the addition of antibody to TNF-alpha. Dialysis experiments determined the
      molecular weight of the factor or factors responsible for the observed effects to
      be greater than 100 kD. The effects of the MCA fibrosarcoma conditioned media
      were abolished by both trypsin treatment and heat inactivation, indicating the
      protein nature of the factor being studied. CONCLUSIONS: A tumor-derived protein
      has been isolated from the MCA fibrosarcoma. The protein inhibits hepatocyte
      albumin production and increases amino acid transport in vitro via the autocrine
      production of TNF-alpha.

PMID- 8857853
TI  - Gender-based mortality follow-up from the Program on the Surgical Control of the
      Hyperlipidemias (POSCH) and meta-analysis of lipid intervention trials. Women in
      POSCH and other lipid trials.
AB  - OBJECTIVE: The authors assessed the clinical results of lipid-lowering therapy in
      women. SUMMARY BACKGROUND DATA: The Program on the Surgical Control of the
      Hyperlipidemias (POSCH) has demonstrated that effective lowering of total
      cholesterol and low-density lipoprotein cholesterol in a postmyocardial
      infarction population significantly reduces atherosclerotic coronary heart
      disease (ACHD) mortality, ACHD mortality combined with a new confirmed nonfatal
      myocardial infarction, and the number of coronary artery bypass grafting and
      angioplasty procedures performed. METHODS: A review and meta-analysis were
      performed of the seven primary or secondary lipid/ atherosclerosis intervention
      trials-including POSCH-published in the English-language literature that included
      women and published results in women separate from the results in men or in the
      entire trial population. The main outcome measure analyzed was overall mortality.
      RESULTS: The Scottish Physicians Clofibrate Study, the Newcastle upon Tyne
      Clofibrate Study, and the Pravastatin Limitation of Atherosclerosis in the
      Coronary Arteries (PLAC I) Trial may have demonstrated a possible benefit in ACHD
      prognosis from effective lipid intervention in women. The other four available
      trials did not. The Minnesota Coronary Survey reported a 15.6% increase in
      overall mortality rate and a 30.6% increase in a combined cardiovascular endpoint
      rate in the lipid-intervention group. The Upjohn Colestipol Study demonstrated
      statistically significant reductions in overall and ACHD mortality in the men,
      but not in the women. The Scandinavian.

PMID- 8857854
TI  - Current status of the use of retroperitoneal approach for reconstructions of the
      aorta and its branches.
AB  - OBJECTIVE: The objective of this article is to determine whether retroperitoneal
      approach for aortic surgery has certain physiologic, technical advantages.
      SUMMARY BACKGROUND DATA: The retroperitoneal approach for abdominal aortic
      reconstruction classically had been reserved for select patients with either high
      risk comorbid disease or specific anatomic problems that preclude the
      transabdominal approach. With increasing appreciation of the physiologic,
      anatomic, and technical advantages of the extended posterolateral retroperitoneal
      approach, the authors have expanded its use for repair of all types of aortic
      visceral and renal artery disease as well as ruptured abdominal aortic aneurysm
      and infected aortic grafts. METHODS: From January 1981 to September 1995, 2340
      retroperitoneal aortoiliac reconstructions were performed in 2243 patients.
      Aortic reconstructions accounted for 1756 cases: 1109 for elective abdominal
      aortic aneurysms, 210 for ruptured and symptomatic aortic aneurysms, 399 for
      occlusive disease, 18 for infected aortic grafts, and 20 for other indications.
      Iliofemoral disease was the indication for 584 procedures. As experience was
      gained, this approach also was used for 417 renal and 50 celiac and superior
      mesenteric artery reconstructions. RESULTS: The mean age was 67 years with 1590
      men and 653 women. Overall mortality was 5.2% for all aortic cases: 2.4% for
      elective, 12.6% for symptomatic, and 29.0% for ruptured aortic aneurysms. Major
      complications occurred in 12.5% of the elective procedures and in 38.3% of
      emergency procedures. Over the past 5 years, the average length of hospital for
      uncomplicated elective abdominal aortic aneurysms was 6.1 days, intensive care
      unit stay was 0.7 day, and diet was resumed by postoperative day 1. Five-year
      graft patency was 99% for aneurysms and 95% for occlusive disease. CONCLUSIONS:
      The retroperitoneal approach offers certain physiologic advantages associated
      with minimal disturbance of gastrointestinal and respiratory function, thereby
      reducing the length of intensive care unit and hospital stay. In addition, its
      technical advantages and flexibility facilitates visceral and juxtarenal aortic
      reconstructions without the need for thoracotomy.

PMID- 8857855
TI  - Resection of nonresectable liver metastases from colorectal cancer after
      neoadjuvant chemotherapy.
AB  - OBJECTIVE: The authors discuss the technique and evaluate the results of an
      aggressive surgical approach in patients with primarily unresectable colorectal
      liver metastases that were downstaged by chronomodulated chemotherapy.
      BACKGROUND: Resection is the best treatment of colorectal liver metastases, but
      it may be achieved in only 10% of patients. In the remaining 90%, survival is
      poor, even after partial response to chemotherapy. Little is known about the
      results of curative hepatectomy in patients whose metastases are downstaged by
      chemotherapy. PATIENTS AND METHODS: Fifty-three patients with colorectal liver
      metastases initially unresectable because of ill located (8), large (8),
      multinodular (24) lesions, or because of extrahepatic disease (13) were
      downstaged by a systemic chronomodulated chemotherapy associating 5-fluorouracil,
      folinic acid and Oxaliplatin to the point that operation could be performed. This
      consisted of a major hepatectomy in 37 patients and a minor resection in 16.
      Associated procedures (including 5 two-stage hepatectomies and 3 pulmonary
      resections) were performed in 25 patients. RESULTS: There was no operative
      mortality. Complications occurred in 14 patients. The cumulative 3- and 5-year
      survival rates were 54% and 40% (according to the type of lesions: ill-located,
      75% and 48%; large, 62% and 62%; multinodular, 54% and 40%; extrahepatic, 43% and
      14%). Hepatic recurrence (34 patients, 64%) was amenable to repeat surgery in 15
      cases. CONCLUSIONS: Liver resection may be achieved in some previously
      unresectable patients with the help of an effective chemotherapy. The benefit in
      survival seems comparable to that obtained with primary liver resection (40% at 5
      years). This therapeutic strategy involves a multimodal approach, including
      repeat hepatectomies and extrahepatic surgery.

PMID- 8857856
TI  - Adenosine reduces postbypass transfusion requirements in humans after heart
      surgery.
AB  - OBJECTIVE: The objective of this study was to determine the effect, if any, of
      adenosine blood cardioplegia on blood component usage after heart surgery.
      SUMMARY BACKGROUND DATA: The most common cause of nonsurgical postcardiopulmonary
      bypass bleeding is platelet dysfunction. For this reason, pharmacologic agents
      are under investigation in an effort to reduce the need for transfusion in this
      setting. METHODS: A posthoc analysis of blood product usage was performed in data
      obtained from a Phase I, single center, open label, randomized study performed in
      63 patients. The trial was designed to test the safety and tolerance of adenosine
      when added to blood cardioplegia in increasing doses to enhance myocardial
      protection. The database provided information regarding the effect of adenosine
      cardioplegia on venous plasma adenosine concentrations, the amount of platelets,
      fresh frozen plasma and packed erythrocytes used, and the association between the
      adenosine dose and postoperative thoracic drainage. RESULTS: The postoperative
      thoracic drainage at 6 hours, 24 hours, and at the time of chest tube removal in
      the high-dose adenosine cardioplegia group was 68%, 76%, and 75% of the placebo
      and low-dose adenosine cardioplegia group (p < 0.05). The highest dose of
      adenosine studied increased baseline adenosine venous plasma levels 360-fold,
      from 0.17 +/- 0.09 mumol/L to 42.30 +/- 11.20 mumol/L (p < 0.05). This marked
      increase was associated with a 68%, 56%, and 58% reduction in platelet, fresh
      frozen plasma, and packed erythrocyte usage, respectively (p < 0.05).
      CONCLUSIONS: In addition to enhancing the heart's tolerance to ischemia,
      adenosine-supplemented cardioplegic solution also may reduce bleeding after
      cardiopulmonary bypass.

PMID- 8857857
TI  - A randomized trial of isonitrogenous enteral diets after severe trauma. An immune
      enhancing diet reduces septic complications.
AB  - OBJECTIVE: The authors randomized patients to an enteral diet containing
      glutamine, arginine, omega-3 fatty acids, and nucleotides or to an
      isonitrogenous, isocaloric diet to investigate the effect of septic outcome. A
      third group of patients, without enteral access but eligible by severity of
      injury, served as unfed controls and were studied prospectively to determine the
      risk of infection. SUMMARY BACKGROUND DATA: Laboratory and clinical studies
      suggest that diets containing specialty nutrients, such as arginine, glutamine,
      nucleotides, and omega-3 fatty acids, reduce septic complications. Unfortunately,
      most clinical trials have not compared these diets versus isonitrogenous,
      isocaloric controls. This prospective, blinded study randomized 35 severely
      injured patients with an Abdominal Trauma Index > or = 25 or a Injury Severity
      Score > or = 21 who had early enteral access to an immune-enhancing diet ([IED]
      Immun-Aid, McGaw, Inc., Irvine, CA; n = 17) or an isonitrogenous, isocaloric diet
      (Promote [Ross Laboratories, Columbus, OH] and Casec [Mead-Johnson Nutritionals,
      Evansville, IN]; n = 18) diet. Patients without early enteral access but eligible
      by severity of injury served as contemporaneous controls (n = 19). Patients were
      evaluated for septic complications, antibiotic usage, hospital and intensive care
      unit (ICU) stay, and hospital costs. RESULTS: Two patients died in the treatment
      group and were dropped from the study. Significantly fewer major infectious
      complications (6%) developed in patients randomized to the IED than patients in
      the isonitrogenous group (41%, p = 0.02) or the control group (58%, p = 0.002).
      Hospital stay, therapeutic antibiotics, and the development of intra-abdominal
      abscess was significantly lower in patients receiving the IED than the other two
      groups. This improved clinical outcome was reflected in reduced hospital costs.
      CONCLUSIONS: An IED significantly reduces major infectious complications in
      severely injured patients compared with those receiving isonitrogenous diet or no
      early enteral nutrition. An IED is the preferred diet for early enteral feeding
      after severe blunt and penetrating trauma in patients at risk of subsequent
      septic complications. Unfed patients have the highest complication rate.

PMID- 8857858
TI  - Functional analysis of grafts from living donors. Implications for the treatment
      of older recipients.
AB  - OBJECTIVE: Living-related liver transplantation (LRLT) has established efficacy
      in children. In a larger recipient, LRLT requires the use of a small graft
      because of limits on the donor hepatectomy. SUMMARY BACKGROUND DATA: The minimum
      graft weight required for successful transplantation has not been well
      established, although a characteristic pattern of graft dysfunction has been
      observed in our patients who receive small grafts. The authors present a
      clinicopathologic study of small liver grafts obtained from living donors.
      METHODS: Clinical and histologic data were reviewed for 25 patients receiving
      LRLT. In five older recipients (small group), the graft represented 50% or less
      of expected liver weight, whereas in 20 others (large group), the graft
      represented at least 60% of expected liver weight. A retrospective analysis of
      graft function was conducted by analyzing clinical parameters and histology.
      RESULTS: In the small group, 2 of 5 grafts (40%) were lost due to poor function,
      leading to one patient death (20% mortality), whereas in the large group, 2 of 20
      grafts (10%) were lost due to arterial thrombosis without patient mortality.
      Early ischemic damage related to transplant was comparable with aspartate
      aminotransferase 203 +/- 23 (small group) and 290 +/- 120 (large group) at 24
      hours (p = not significant). Early function was significantly decreased in the
      small group, with prothrombin time 18.2 +/- 2.2 seconds versus 14.8 +/- 1.6
      seconds (large group) on day 3 (p = 0.034). All small group patients developed
      cholestasis with significantly increased total bilirubin levels at day 7 (16 +/-
      5.2 mg% vs. 3.7 +/- 2.7 mg%; p = 0.021) and day 14 (12.0 +/- 7.4 vs. 1.8 +/- 0.7;
      p = 0.021) compared with the large group. Protocol biopsies in the small group
      revealed a diffuse ischemic pattern with cellular ballooning on day 7, which
      progressed to cholestasis in subsequent biopsies. Large group biopsies showed
      minimal ischemic changes. Three small group patients recovered with normal liver
      function by 12 weeks. CONCLUSIONS: Clinical recovery after a small-for-size
      transplant is characterized by significant functional impairment associated with
      paradoxical histologic changes typical of ischemia. These changes apparently are
      due to graft injury, which can only be the result of small graft size. These
      findings have significant implications for the extension of LRLT to adults.

PMID- 8857859
TI  - Expression of secreted platelet-derived growth factor-B by recombinant
      nonreplicating and noncytopathic vaccina virus.
AB  - OBJECTIVE: The purpose of this study was to develop a noncytopathic vector for
      transient delivery of biologically active platelet-derived growth factor (PDGF)
      to wounds. BACKGROUND: Topical application of the protein PDGF-B has improved
      wound healing in experimental studies of healing-impaired wounds. However, use of
      PDGF-B has been limited by availability of recombinant protein, short half-life,
      and inability to reliably apply to the wounded area. One approach to supply local
      PDGF-B is through transient gene transfer and expression. METHODS: Treatment of
      vaccinia virus with psoralen and long-wave ultraviolet irradiation makes it
      noncytopathic and nonreplicative. The authors inserted various transgenes
      encoding different forms of PDGF into recombinant vaccinia virus at the
      hemaglutinin locus by homologous recombination. Because the PDGF-B expressed from
      full length cDNA is not secreted because of the membrane retention sequence at
      the C-terminal end of the polypeptide, the authors inserted a 3'-truncated form
      of human PDGF-B cDNA in recombinant vaccinia virus to achieve secretion. To avoid
      interference in bioassays by a virally encoded epidermal growth factor homologue
      called vaccinia growth factor (VGF) in wild type vaccinia virus (CR-19), we used
      a VGF-negative strain to express PDGF-B (vSC20PDGF-B). Biologic activity of PDGF
      was tested by measuring proliferation of a 3T3 fibroblast cell line. RESULTS:
      Supernatant from CR-19-infected cells (VGF+) and from truncated vSC20PDGF
      infected cells caused mild and marked proliferation of 3T3 cells, respectively,
      whereas supernatant from full-length vSC20PDGF virally infected cells did not.
      Furthermore, in vitro infection of a confluent 3T3 monolayer with noncytopathic
      and nonreplicative vaccinia encoding either VGF or truncated PDGF also caused
      similar proliferation. CONCLUSIONS: These results provide important preliminary
      evidence for the ability to treat nonhealing wounds with nonreplicating and
      noncytopathic recombinant vaccinia viruses encoding cytokine growth factors.

PMID- 8857860
TI  - Effect of resection margins on the recurrence of Crohn's disease in the small
      bowel. A randomized controlled trial.
AB  - OBJECTIVE: The authors assess the effect of surgical margin width on recurrence
      rates after intestinal resection of Crohn's Disease (CD). BACKGROUND: The optimal
      width of margins when resecting DC of the small bowel is controversial. Most
      studies have been retrospective and have had conflicting results. METHODS:
      Patients undergoing ileocolic resection for CD (N = 152) were randomly assigned
      to two groups in which the proximal line of resection was 2 cm (limited
      resection) or 12 cm (extended resection) from the macroscopically involved area.
      Patients also were classified by whether the margin of resection was
      microscopically normal (category 1), contained nonspecific changes (category 2),
      were suggestive but not diagnostic for CD (category 3), or were diagnostic for CD
      (category 4). Recurrence was defined as reoperation for recurrent preanastomotic
      disease. RESULTS: Data were collected on 131 patients. Median follow-up time was
      55.7 months. Disease recurred in 29 patients: 25% of patients in the limited
      resection group and 18% of patients in the extended resection group. In the 90
      patients in category 1 with normal tissue, recurrence occurred in 16, whereas in
      the 41 patients with some degree of microscopic involvement, recurrence occurred
      in 13. Recurrence rates were 36% in category 2, 39% in category 3, and 21% in
      category 4. No group differences were statistically at the 0.01 level.
      CONCLUSION: Recurrence of CD is unaffected by the width of the margin of
      resection from macroscopically involved bowel. Recurrence rates also do not
      increase when microscopic CD is present at the resection margins. Therefore,
      extensive resection margins are unnecessary.

PMID- 8857861
TI  - Retirement age and the work force in general surgery.
AB  - OBJECTIVE: This study examines the age of retirement of general surgery Fellows
      of the American College of Surgeons from 1984 through 1995 and analyzes the
      potential effect on the work force in general surgery of age of retirement.
      SUMMARY BACKGROUND DATA: Data from the Fellowship files of the American College
      of Surgeons, the American Board of Medical Specialties, and the American Medical
      Association disclosed that the number of practicing general surgeons in the
      United States in 1994 was between 17,289 and 23,502, or approximately 7 general
      surgeons per 100,000 population in the United States. METHODS: The Fellowship
      files of the American College of Surgeons from 1984 through 1995 were searched
      for general surgeons who had written to ask for retirement status or who had died
      before retirement. Calculations were made of the effect of years in practice on
      the total general surgeon work force. All living retirees from 1984 to 1985 and
      1994 to 1995 were questioned to learn the factors leading to a decision to
      retire. RESULTS: The average age of retirement for general surgeon Fellows has
      risen from 60.45 in 1984 to 62.97 in 1995. Because of increasing diversion of
      general surgery graduates into surgical specialties, total practice years are
      declining despite increasing length of practice time. The principal factors for
      retirement decisions in 1984 and 1985 were disability (26%), leisure time (20%),
      and unfavorable changes in surgery (29%). In 1994 and 1995, disability was a
      major factor in 14% of decisions, leisure time in 20%, and unfavorable changes in
      surgery in 56%. CONCLUSIONS: Fewer general surgeons enter the work force each
      year. Thus, despite working longer, the total number of years practiced by each
      cohort of new general surgeons has decreased.

PMID- 8857862
TI  - Improved outcome of surgical flaps treated with topical dimethylsulfoxide.
AB  - OBJECTIVE: The objective of this study was to analyze the effect of
      dimethylsulfoxide (DMSO) on skin flap viability. BACKGROUND: Dimethylsulfoxide
      has been shown to decrease necrosis of random skin flaps in the rat model, but no
      human studies have been performed. The authors performed a randomized,
      prospective study on the effect of DMSO on skin flap viability in patients
      undergoing mastectomy and inguinal lymphadenectomy. METHODS: Twenty-four patients
      had topical 60% DMSO applied to their flaps every 4 hours x 10 days after
      operation and 27 patients had operation alone. The maximum area of flap ischemia
      was traced by a masked observer and measured by cut and weigh technique.
      Significance of differences between the treatment and control group was
      determined by Student's test. RESULTS: The mean area of ischemia for the DMSO
      group was 16.33 U versus 44.93 U for the control group. This difference was
      statistically significant (p = 0.01). CONCLUSIONS: The authors conclude that
      topical application of DMSO reduces skin flap ischemia in humans and recommend
      its use after operation in which skin flaps are created.

PMID- 8857863
TI  - Peering into the 'black box'. Measuring outcomes of managed care.
AB  - Research on the impact of managed care on access, quality, outcomes, and costs of
      mental health and substance abuse services has been limited because of the lack
      of generalizability of studies, the "black box" focus of much of the research,
      the dynamic changes in mental health and substance abuse managed care, and the
      proprietary nature of the health care industry. This article provides a framework
      for understanding the organizational, financial, and procedural features of
      health plans and the effect of these features on the characteristics and flow of
      patients through health plans and the selection and utilization of treatments.
      The diverse research priorities of key stakeholders, i.e., public and private
      purchasers, managed care organizations, providers, and patients and their
      families, are described along with a broader societal agenda for delineating the
      outcomes of health care plans. Critical research and methodologic issues in
      studying the effects of managed care are outlined, including issues related to
      identifying and selecting appropriate outcome measures and developing appropriate
      methods for risk adjustment to adequately control for patient selection bias.
      This article asserts that government, purchasers, health care plans, providers,
      consumers, and researchers must collaboratively develop resources and research
      approaches to fully evaluate the effects of managed care. To realize this
      objective, auspices with reasonable objectivity are needed along with access to
      necessary data within the black box of health care systems, a cadre of trained
      investigators, and sufficient research funding, including the development of an
      all payers fund to support clinical and health services research.

PMID- 8857864
TI  - Subthreshold psychiatric symptoms in a primary care group practice.
AB  - BACKGROUND: The authors define 6 groups of subthreshold psychiatric symptoms that
      do not meet the full criteria for a DSM-IV Axis I disorder and examine the
      clinical significance of these symptoms in an outpatient primary care sample.
      METHODS: The subjects were 1001 adult primary care patients in a large health
      maintenance organization. Data on sociodemographic characteristics and functional
      impairment, including scores on the Sheehan Disability Scale, were collected at
      the time of the medical visit, and a structured diagnostic interview for DSM-IV
      disorders was completed by telephone within 4 days of the visit. Subthreshold
      symptoms were defined for depressive, anxiety, panic, obsessive-compulsive, drug,
      and alcohol symptoms. RESULTS: Subthreshold symptoms were as or more common than
      their respective Axis I disorders: panic (10.5% vs 4.8%), depression (9.1% vs
      7.3%), anxiety (6.6% vs 3.7%), obsessive-compulsive (5.8% vs 1.4%), and alcohol
      (5.3% vs 5.2%) and other drug (3.7% vs 2.4%) cases. Patients with each of the
      subthreshold symptoms had significantly higher Sheehan Disability Scale scores
      (greater impairment) than did patients with no psychiatric symptoms. Many
      patients (22.6%-53.4%) with subthreshold symptoms also met the full criteria for
      other Axis I disorders. After adjusting for the confounding effects of other Axis
      I disorders, other subthreshold symptoms, age, sex, race, marital status, and
      perceived physical health status, only depressive symptoms, major depressive
      disorder, and, to a lesser extent, panic symptoms were significantly correlated
      with the impairment measures. CONCLUSIONS: In these primary care patients, the
      morbidity of subthreshold symptoms was often explained by confounding mental,
      physical, or demographic factors. However, depressive symptoms and, to a lesser
      extent, panic symptoms were disabling even after controlling for these factors.
      Primary care clinicians who detect subthreshold psychiatric symptoms should
      consider a broad psychiatric assessment.

PMID- 8857865
TI  - Comorbid anxiety disorder and the functioning and well-being of chronically ill
      patients of general medical providers.
AB  - BACKGROUND: The comorbidity of psychiatric disorders with chronic health
      conditions has emerged as a topic of considerable clinical and policy interest,
      in part owing to the evidence that anxiety disorders themselves are associated
      with morbidity. However, the implications for health-related quality of life that
      result from anxiety disorders, which are comorbid to chronic medical or
      psychiatric illness, are not well understood, especially in primary care samples.
      METHODS: A 2-year observational study of 875 adult patients with hypertension,
      diabetes, heart disease, and current depressive disorder or subthreshold
      depression receiving care from general medical providers was conducted. The
      unique effect of any comorbid anxiety disorder on functioning and well-being
      (determined with the use of the 36-Item Short-Form Health Survey [SF-36]) was
      estimated, as well as the differential impact at baseline, 2-year follow-up, and
      change over time, of any comorbid anxiety disorder for patients with chronic
      medical conditions or depression. RESULTS: Patients with comorbid anxiety who
      received general medical care had lower levels of functioning and well-being than
      those without comorbid anxiety. These differences were most pronounced in mental
      health-related quality-of-life measures and when anxiety was comorbid with
      chronic medical conditions rather than with depression. Hypertensive and diabetic
      patients with comorbid anxiety were as debilitated as patients with depression or
      heart disease, and this low health-related quality of life persisted over time.
      Comorbid anxiety had less of an effect on patients with heart disease who already
      had a low health-related quality of life. CONCLUSION: The finding of substantial
      differences in the quality of life between hypertensive and diabetic patients
      with and without comorbid anxiety disorder highlights the clinical and societal
      importance of identifying comorbid anxiety in these patients.

PMID- 8857866
TI  - Medical costs attributed to depression among patients with a history of high
      medical expenses in a health maintenance organization.
AB  - BACKGROUND: While previous studies have compared medical utilization between
      depressed and nondepressed patients, we conducted a study that focused
      specifically on patients who had a history of high medical expenditures. METHODS:
      This study was designed to determine whether a positive screen for depression is
      predictive of continued high medical expenditures. Medical utilization data were
      obtained on 50,000 patients enrolled in the DeanCare health maintenance
      organization for 2 consecutive years. Consistent high utilizers were identified
      based on the medical utilization costs (paid by the health maintenance
      organization) for those 2 consecutive years, 1992 and 1993. A depression screen
      based on the Medical Outcomes Survey was mailed to 786 high utilizers. Their
      costs were determined for 1994. Regression analyses identified 1994 costs
      associated with depression, adjusting for age, sex, benefits package, and medical
      comorbidity. RESULTS: Depressed high utilizers were more likely than nondepressed
      high utilizers to have higher medical costs in 1994. Among high utilizers,
      depressed patients' 1994 costs were significantly higher ($5764 vs $4227; P <
      .001), although expenditures for depressed and nondepressed high utilizers were
      similar for the previous 2 years. The total medical cost associated with
      depression in 1994, adjusted for age, sex, benefits package, and medical
      comorbidity, was $1498 per patient. CONCLUSIONS: In the third year (1994), a
      positive Medical Outcomes Survey screen for depression in high utilizers was
      associated with $1498 in higher medical costs. The average actual amount spent on
      depression treatment accounted for only a small portion of total medical costs
      for depressed high utilizers in the third year.

PMID- 8857867
TI  - Counseling typically provided for depression. Role of clinician specialty and
      payment system.
AB  - BACKGROUND: To assess how current policy trends may affect the use of counseling
      for depression, we examined the variation in the use of counseling and usual
      clinician counseling style for depression across specialty sectors (psychiatry,
      psychology, and general medicine) and reimbursement type (fee-for-service or
      prepaid). METHODS: Three types of observational data from the RAND Medical
      Outcomes Study: (1) patient-reported demographics, depressive symptoms, clinical
      status, and perceptions about participation style; (2) clinician reports of
      counseling during specific patient encounters; and (3) clinician reports of the
      usual counseling and interpersonal style across patients who were seen in a
      practice. RESULTS: While almost all depressed patients who were being treated by
      mental health specialists received brief counseling for at least 3 minutes, less
      than half of the depressed patients in the general medical sector received such
      counseling--even for those patients with a current depressive disorder.
      Counseling rates were lower under prepaid than fee-for-service care in general
      medical practices. Psychiatrists relied more on psychodynamic approaches, and
      psychologists relied more on behavioral therapies relative to each other, but
      both specialty groups provided longer sessions and used more formal
      psychotherapeutic techniques (e.g., interpretation) than did general medical
      clinicians. Clinicians who were treating more patients who had prepaid plans
      reported a lower proclivity for face-to-face counseling, and they spent less time
      when they were counseling patients compared with clinician who were treating more
      patients who had fee-for-service plans; however, these differences were not
      large. CONCLUSION: The use of counseling in the usual care for depression varied
      by both specialty and payment system, while the usual clinician counseling style
      differed markedly by specialty, but only slightly by payment system.

PMID- 8857868
TI  - Treating major depression in primary care practice. Eight-month clinical
      outcomes.
AB  - BACKGROUND: We studied whether standardized treatments of major depression whose
      efficacy was established with psychiatric patients are equally effective when
      provided to primary care patients, and whether standardized treatments are more
      effective than a primary care physician's usual care. METHODS: A randomized
      controlled trial was conducted, in which primary care patients meeting DSM-III-R
      criteria for a current major depression were assigned to nortriptyline (n = 91)
      or interpersonal psychotherapy (n = 93) provided within well-structured
      parameters, or a physician's usual care (n = 92). The main outcome measures were
      degree and rate of improvement in severity of depressive symptoms and proportion
      of patients recovered at 8 months. RESULTS: Severity of depressive symptoms was
      reduced more rapidly and more effectively among patients randomized to
      pharmacotherapy or psychotherapy than among patients assigned to a physician's
      usual care. Among treatment completers, approximately 70% of patients
      participating in the full pharmacotherapy or psychotherapy protocol but only 20%
      of usual care patients were judged as recovered at 8 months. CONCLUSIONS:
      Pharmacotherapy and psychotherapy effectively treat major depression among
      primary care patients when provided within specific parameters and for the full
      acute and continuation phases. Treatment principles recommended by the Depression
      Guideline Panel of the Agency for Health Care Policy and Research are supported.

PMID- 8857869
TI  - A multifaceted intervention to improve treatment of depression in primary care.
AB  - BACKGROUND: This research study evaluates the effectiveness of a multifaceted
      intervention program to improve the management of depression in primary care.
      METHODS: One hundred fifty-three primary care patients with current depression
      were entered into a randomized controlled trial. Intervention patients received a
      structured depression treatment program in the primary care setting that included
      both behavioral treatment to increase use of adaptive coping strategies and
      counseling to improve medication adherence. Control patients received "usual"
      care by their primary care physicians. Outcome measures included adherence to
      antidepressant medication, satisfaction with care of depression and with
      antidepressant treatment, and reduction of depressive symptoms over time.
      RESULTS: At 4-month follow-up, significantly more intervention patients with
      major and minor depression than usual care patients adhered to antidepressant
      medication and rated the quality of care they received for depression as good to
      excellent. Intervention patients with major depression demonstrated a
      significantly greater decrease in depression severity over time compared with
      usual care patients on all 4 outcome analyses. Intervention patients with minor
      depression were found to have a significant decrease over time in depression
      severity on only 1 of 4 study outcome analyses compared with usual care patients.
      CONCLUSION: A multifaceted primary care intervention improved adherence to
      antidepressant regimens and satisfaction with care in patients with major and
      minor depression. The intervention consistently resulted in more favorable
      depression outcomes among patients with major depression, while outcome effects
      were ambiguous among patients with minor depression.

PMID- 8857870
TI  - Some economics of mental health 'carve-outs'.
AB  - We discuss the rationale for benefit carve-out contracts in general and for
      mental health and substance abuse in particular. We focus on the control of
      adverse selection as a principal explanation and find that this is consistent
      with the wide-spread use of sole-source contracting with periodic rebidding. We
      also find that some degree of risk sharing is common; we interpret this as a
      method of balancing cost-containment incentives with incentives to maintain
      access and quality on unmeasured dimensions.

PMID- 8857871
TI  - Enrollment duration, service use, and costs of care for severely mentally ill
      members of a health maintenance organization.
AB  - BACKGROUND: The rapid growth of prepaid health care and the increasing enrollment
      of Medicaid clients in health maintenance organizations (HMOs) raise concerns
      about the adequacy of services for persons with severe mental illness in
      capitated health plans. Uncontrolled studies have suggested that enrollment of
      HMO members with mental illness may be prematurely terminated. METHODS: We
      identified 250 adult Kaiser Permanente Northwest Region (Portland, Ore) members
      who were enrolled during 1986 or 1987 and had chart diagnoses of schizophrenia or
      bipolar disorder. Severely mentally ill subjects were matched by age and sex with
      control HMO members with and without diabetes mellitus. Records of the HMO and
      the state mental health agency were reviewed to determine HMO enrollment
      duration, private and public service utilization, and HMO costs of care during
      the 4-year follow-up period. RESULTS: The severely mentally ill subjects had 42
      months of HMO enrollment during the follow-up period compared with 37 months for
      the controls without diabetes mellitus and 47 months for the patients with
      diabetes mellitus (P < .001). When HMO enrollment prior to the study was taken
      into account, the severely mentally ill subjects and those with diabetes mellitus
      had similar membership duration. Among the severely mentally ill subjects,
      community mental health service use was related to longer duration of HMO
      enrollment (P < .05) but HMO costs of care per member per month were not related
      to retention. The severely mentally ill subjects were high users of mental health
      services but their use of general medical care was similar to that of the
      controls without diabetes mellitus. CONCLUSIONS: This controlled study found no
      evidence for early termination of HMO members with costly mental illness. Use of
      community mental health care was associated with longer duration of HMO
      enrollment.

PMID- 8857872
TI  - Managing the care of schizophrenia. Lessons from a 4-year Massachusetts Medicaid
      study.
AB  - BACKGROUND: In 1992, Massachusetts launched a state-wide managed care plan for
      all Medicaid beneficiaries. METHODS: This retrospective, multi-year, cross
      sectional study used administrative data from the Massachusetts Division of
      Medical Assistance and Department of Mental Health, consisting of claims for
      16,400 disabled adult patients insured by Medicaid in Massachusetts between July
      1, 1990, and June 30, 1994. The main outcome measures include annual rates of
      hospitalization, emergency department utilization, and follow-up care 30 days
      after discharge; length of inpatient stay; and per-person inpatient and
      outpatient expenditures. RESULTS: Between 1991 and 1994, the likelihood of an
      inpatient admission decreased from 29% to 24% and was accompanied by a slight
      reduction in length of stay (median number of bed-days per admission dropped by
      3.3 days). There was a slight decrease in the number of patients who sought care
      in general hospital emergency department utilization. However, there was a small
      increase in the fraction of patients readmitted within 30 days of discharge.
      Medicaid and Department of Mental Health expenditures for mental health per
      treated beneficiary decreased slightly, from $11,060 to $10,640, during the 4
      year study period. CONCLUSION: Although per-person expenditures dropped and most
      patient patterns of care remained the same, longer-term study is recommended to
      asses whether the trends can be maintained.

PMID- 8857873
TI  - Cost-effectiveness of clozapine monitoring after the first 6 months.
AB  - BACKGROUND: Clozapine is effective in treating patients with schizophrenia who do
      not respond to conventional neuroleptic drugs. The drug is unique in that it is
      available only with a US Food and Drug Administration-mandated system for weekly
      monitoring of patients' white blood cell counts. No study has been conducted to
      evaluate the cost-effectiveness of this mandatory monitoring system. METHODS: A
      benchmark case was established by utilizing cumulative incidence rates of
      agranulocytosis from a recent study with a large sample of clozapine-treated
      patients. We assumed a 20% mortality among patients with agranulocytosis, $30.61
      in monitoring costs each week, and 14.4 years of remaining life expectancy after
      detection of agranulocytosis. Based on these bench-mark assumptions, cost
      effectiveness ratios in dollars per quality-adjusted life-year were calculated
      for the first, second, and third 6-month periods during which a patient was
      receiving clozapine. Sensitivity analyses were performed with more conservative
      assumptions in 5 alternative scenarios. RESULTS: In the benchmark case, costs per
      quality-adjusted life-year gained were $61,694, $925,418, and $420,644 for the
      first, second, and third 6-month periods of clozapine treatment, respectively. In
      the alternative scenarios, these costs ranged from $7923 to $46,056 for the first
      6-month period and from $54,025 to $690,850 for the second and third 6-month
      periods. CONCLUSIONS: While the costs of monitoring patients with schizophrenia
      in the first 6-month period of clozapine treatment seem to be justifiable,
      monitoring thereafter may not be cost-effective because of the very low incidence
      of agranulocytosis in the later periods.

PMID- 8857874
TI  - A funny thing happened on the way to reform.

PMID- 8857875
TI  - TPH replication study: not!

PMID- 8857876
TI  - Educational performance and vocational participation after spinal cord injury in
      childhood.
AB  - OBJECTIVE: To examine educational achievement and vocational success of children
      with SCI. DESIGN: Surveys administered to students and teachers, and content
      analysis of school records. SETTING: Regional pediatric rehabilitation program.
      PARTICIPANTS: Participants were selected from 144 children with SCI treated from
      1979 through 1992; 98 met inclusion criteria of onset of SCI before the age of 18
      years, older than 3 years, residual paresis, and no cognitive impairment; 29%
      were lost to follow-up, and 53 of the 70 contacted were enrolled. MAIN OUTCOME
      MEASURES: School completion rates, absenteeism, grades, ratings of participation;
      education and living situations after high school; history of paid employment.
      RESULTS: The 53 responders were: 33 boys, 20 girls; 25 with paraplegia (47%), 28
      with tetraplegia (53%); mean length of disability = 9.4 years; 12 primary
      students (23%), 19 secondary students (36%), and 22 postsecondary participants
      (41%). Students and teachers rated student participation and performance as
      average or above compared to peers; 84% of secondary students planned to attend
      college after graduation. Only 33% of high school students over age 15 had been
      employed. Ninety-one percent of postsecondary subjects had graduated from high
      school. Seven (32%) had graduated from college or a vocational program, 11 (50%)
      were enrolled in college full- or part-time, and 4 others (18%) were neither in
      school nor employed. Current employment rates were 71% of college graduates, 36%
      of those in college, and 0% of those who had never enrolled. Level of SCI was not
      related to employment. CONCLUSIONS: Students with SCI demonstrate adequate
      participation and performance in educational settings, but may benefit from more
      vocational counseling and opportunities for paid employment.

PMID- 8857877
TI  - Preloading and range of motion effect on plantarflexor muscle performance.
AB  - OBJECTIVE: To determine the effects of maximal preloading and range of motion
      (ROM) on the mechanical parameters of the plantarflexor muscles obtained while
      using the isotonic mode of testing of a Biodex dynamometer. DESIGN: A convenience
      sample of healthy subjects in the context of a descriptive comparative study.
      SETTING: Research laboratory in Canada. SUBJECTS: Fifteen volunteered subjects
      without history of injury or disorder to the right lower extremity. MEASUREMENTS:
      Four maximal isotonic tests were performed against a selected load of 27Nm. For
      the first two tests, the movement at the ankle ranged from -12 degrees
      (dorsiflexion) to +32 degrees (plantarflexion); one of these tests was preceded
      by a 2-second maximal preloading contraction, while the other was performed
      without preloading. For the other two tests, the ROM at the ankle was increased
      by 15 degrees of plantarflexion and thus ranged from -12 degrees to +47 degrees;
      again one of these tests was executed with preloading and the other without
      preloading. RESULTS: The four tests showed differences in the mechanical
      parameters (MANOVA p < .05). At angles of -10 degrees and +5 degrees, subjects
      produced higher torque and power but lower velocity values for the two tests
      preceded by a maximal preloading. The effect of ROM was demonstrated at +20
      degrees where tests performed in a small amplitude reached a lower velocity than
      the corresponding tests performed in a larger amplitude. Based on the velocity
      profiles, the results also revealed that maximal preloading changed the selected
      isotonic movement of the Biodex dynamometer to an isoaccelerative movement
      characterized by high torque and power production. CONCLUSIONS: Isotonic
      assessment using the Biodex dynamometer provides different values of torque,
      velocity, and power depending on the testing conditions used. In clinical
      settings, it would be important to control these testing conditions.

PMID- 8857878
TI  - Home use of a functional electrical stimulation system for standing and mobility
      in adolescents with spinal cord injury.
AB  - OBJECTIVE: Functional electrical stimulation (FES) is a technology that may allow
      some patients with spinal cord injury (SCI) to integrate standing and upright
      mobility with wheelchair mobility. The purpose of this study was to document the
      patterns of home and community use of a FES system for standing and mobility.
      DESIGN: A telephone questionnaire was administered every 1 to 4 weeks for a
      minimum of 1 year. An interview was given at the end of the study to probe the
      motivators and barriers to home use. SETTING: Training for use of the FES system
      was performed in an inpatient pediatric rehabilitation setting. Data collection
      began after the subjects were discharged to home. PARTICIPANTS: Five adolescents
      with complete, thoracic-level SCI. INTERVENTION: Subjects participated in a
      program of FES exercise followed by training in basic mobility skills such as
      standing transfers, maneuvering, level ambulation, one-handed and reaching
      activities, and stair ascent/descent. MAIN OUTCOME MEASURE: The frequency with
      which the FES system was used at home and the activities for which it was
      utilized were documented. Motivators and barriers to FES home use were examined.
      RESULTS: Subjects donned the FES system on the average once every 3 to 4 days.
      Between 51% and 84% of the times donned, the system was used for exercise. The
      remaining times it was used for standing activities, most commonly reaching, one
      handed tasks, and standing for exercise. "Motivators" included being able to do
      things that would otherwise be difficult, perceiving a healthful benefit or a
      sense of well-being from standing and exercise, and feeling an obligation to
      stand as a participant in a research study. "Barriers" to FES use included not
      finding time to use the system, having difficulty seeing opportunities to stand,
      and being reluctant to wear the FES system all day.

PMID- 8857879
TI  - Clinical use of percutaneous intramuscular electrodes for functional electrical
      stimulation.
AB  - OBJECTIVE: To evaluate the clinical use of the percutaneous intramuscular
      electrode in functional electrical stimulation (FES). DESIGN: Randomized and
      controlled study. SETTING: A referral center and institutional practice providing
      outpatient care. PATIENTS: Seventeen patients (12 men, 5 women) who had implanted
      percutaneous intramuscular electrodes for more than 1 year were examined. The
      average follow-up time after implantation of electrodes was 2.2 years (range, 1yr
      to 4yr 10mo). Overall, there were 327 electrodes (83 upper extremities and 244
      lower extremities). INTERVENTION: The indwelling electrode was composed of
      helically coiled Teflon-coated rope stranded from 19 hard drawn wires of SUS 316L
      stainless steel (SES 114). MAIN OUTCOME MEASURES: The rates of breakage,
      movement, and infection, and the number of electrodes that needed reimplantation
      were evaluated. RESULTS: Only one electrode broke (0.3%) in the iliopsoas muscle
      at 12 weeks after implantation. Eight electrodes (2.4%) were removed because of
      loss of sufficient contraction force caused by movement of the electrodes.
      Movements occurred at 9 weeks in 6 electrodes and at 5 months in two. The failure
      rate of electrodes in the lower extremities was 3.7%. No failures occurred in the
      upper extremities. Ten electrodes (3.1%) required reimplantation. Although ten
      superficial infections (3.1%) were seen around the site of electrode insertion,
      no removals of electrode were needed. All electrodes in one patient were removed,
      however, because of generalized methicillin-resistant Staphylococcus aureus
      infection complicated with renal disease. Electrodes were reimplanted after
      improvement of the infection. CONCLUSIONS: The ultrafine percutaneous
      intramuscular electrode was considered practical for long-term FES use.

PMID- 8857880
TI  - Male and female performance on the assessment of motor and process skills.
AB  - OBJECTIVE: To examine the validity of the assertion that men and women do not
      differ significantly on the Assessment of Motor and Process Skills (AMPS), a
      functional assessment tool used to evaluate the interaction between component
      motor and process skills and IADL (instrumental or domestic activities of daily
      living) performance capacity. DESIGN: Descriptive comparison. Using many-faceted
      Rasch analysis, the AMPS motor and process scales were examined for differential
      item response between gender subgroups. Mean motor and process ability measures
      of age-matched groups of male and female subjects were also compared.
      PARTICIPANTS: A convenience sample of more than 3,500 men and women from the
      standardization sample for the pilot version of the AMPS computer-scoring
      software. The subjects had a variety of physical disabilities or psychiatric
      diagnoses. MAIN OUTCOME MEASURES: Hypotheses were as follows: (1) no differential
      item response would be found on the motor or process scales; (2) if differential
      item response was found, it would not have an impact on the final estimation of
      client ability; (3) men and women would not differ in mean AMPS motor or process
      ability. RESULTS: Of the 36 AMPS items, only one (Lifts) differed between men and
      women. This differential item response did not disrupt the final estimation of
      client ability. Men and women did not differ in mean motor ability. Women on the
      whole were more able than men in mean process ability. CONCLUSIONS: The AMPS is
      valid for use across gender subgroups. Men and women do not differ in AMPS motor
      ability, but overall, women are slightly more able than men in AMPS process
      ability.

PMID- 8857881
TI  - Fear of falling revisited.
AB  - OBJECTIVE: To evaluate the measurement properties of an expanded version of the
      Falls Efficacy Scale (FES)-a measure of fear of falling. The original FES
      measures fear on almost exclusively indoor activities, which may limit the
      usefulness of the scale in identifying early stages of fear of falling in active
      community-dwelling older people. DESIGN: Two-group convenience sample. SETTING:
      An outpatient referral clinic, and community-dwelling older people recruited from
      various sources. SUBJECTS: A volunteer sample of 111 healthy community-dwelling
      elderly (mean age 74.0 years) and a sample of 68 older people referred to a Falls
      and Balance Clinic (FBC) (mean age 79.2). Twenty-one subjects (9 healthy elderly
      and 12 FBC patients) were tested twice 1 week apart to investigate retest
      reliability. MAIN OUTCOME MEASURES: A 14-activity questionnaire (the Modified
      Falls Efficacy Scale [MFES]) was used that incorporated the original 10-activity
      FES and four additional activities. Falls efficacy was rated on a 10-point visual
      analogue scale for each activity. RESULTS AND CONCLUSIONS: The MFES demonstrated
      high internal consistency (Cronbach's alpha.95) and less skew than the original
      FES (-2.4 and -3.3, respectively). Factor analysis of the MFES revealed two
      factors accounting for 75% of the sample variance, grouping into an "indoor type
      activity" factor and an "outdoor type activity" factor. Retest reliability for
      the MFES was high (intraclass correlation coefficients = .93). Significant
      differences were evident between the FBC group and the healthy older group on all
      items of the MFES and on the total MFES score (p < .05). On the basis of these
      preliminary findings, the MFES appears to be a reliable and valid measure of
      falls self-efficacy, and could be a useful addition in the comprehensive
      assessment of older people with balance disturbance or falls.

PMID- 8857882
TI  - Rehabilitation of elderly fallers: pilot study of a low to moderate intensity
      exercise program.
AB  - OBJECTIVE: The role of exercise in the prevention of falls and fall-related
      injuries among elderly persons is unclear. The objective of this study was to
      assess the response to an exercise-based rehabilitation program intended to
      improve balance and mobility and reduce or prevent falls. DESIGN: Pretest
      posttest experimental design with repeated measures at baseline, immediately
      postintervention, and 6 months postintervention. To assess the effect of repeated
      exposure to our main outcome measure (the obstacle course), half of the
      participants (randomly selected) were allowed to practice on the obstacle course.
      SETTING: A veterans affairs medical center. PARTICIPANTS: Elderly, ambulatory,
      community-dwelling volunteers recruited from among local outpatients at our
      medical center. INTERVENTION: Sixty-five volunteers completed a 6-week supervised
      low to moderate intensity program of stretching, postural control, endurance
      walking, and coordination exercises designed to improve balance and mobility.
      Participants were divided into 2 groups: 34 participants who did not practice on
      the obstacle course during their exercise program and 31 participants who
      practiced on the obstacle course in addition to their otherwise identical
      exercise program. MAIN OUTCOME MEASURES: Performance on a functionally oriented
      obstacle course and self-reported falls and fall-related injuries. RESULTS: No
      significant performance differences were found between the two groups. After
      intervention, mean qualitative obstacle course scores improved modestly (5%) and
      mean obstacle course completion time decreased by 15% from baseline. These
      postintervention pairwise performance differences were clinically important but
      not statistically significant. Relative to baseline levels, postintervention
      falls and injuries did not change significantly. CONCLUSIONS: Our exercise
      intervention may have the potential to improve functional performance. However,
      some modifications are necessary to enhance efficacy. The obstacle course may be
      a useful tool in the evaluation of elderly persons with balance and mobility
      impairment in the rehabilitation setting.

PMID- 8857883
TI  - Inpatient hospital utilization among veterans with traumatic spinal cord injury.
AB  - OBJECTIVE: To describe the pattern of inpatient hospital utilization, up to 15
      years after injury, among a cohort of veterans with service-connected traumatic
      spinal cord injury (SCI). PATIENTS: A cohort of 1,250 male veterans, with
      traumatic SCI occurring between 1970 and 1986, who visited the VA within 1 year
      of injury, was assembled from VA administrative files; diagnosis was verified by
      examining hospital discharge summaries. DESIGN: Computerized record linkage among
      Department of Veterans Affairs (VA) administrative files was used to determine
      patterns of inpatient hospital utilization. MAIN OUTCOME MEASURE: Pattern of
      inpatient admissions and length of stay (LOS). RESULTS: Patients were typically
      white males injured in their mid-twenties. The initial VA hospitalization began
      approximately 6 weeks after injury and lasted 4 to 7 months, depending on injury
      level and completeness. Subsequent hospitalizations usually lasted approximately
      10 days, but 22% of stays exceeded 1 months. Most hospitalizations took place in
      specialized SCI Centers. Comparing the 1980s with the 1970s, patients in the
      1980s entered VA facilities sooner after injury, were more likely to visit SCI
      Centers, and had shorter initial stays. Rates for the incidence of
      rehospitalization decreased rapidly in years 2-5 after injury and declined less
      rapidly thereafter. Occupancy rates and proportion rehospitalized followed
      similar patterns. The incidence rate for persons with complete quadriplegia was
      approximately twice that of patients with incomplete paraplegia. Between 1970 and
      1991, both the rehospitalization incidence rate and LOS decreased by
      approximately 20%. Only 10% of patients accounted for 46% of the total LOS. LOS
      during the first five years was predictive of later LOS. CONCLUSIONS: The pattern
      of rehospitalization in VA facilities was generally consistent with that of the
      Model Systems. Efforts toward preventing rehospitalization should target persons
      with previous high utilization.

PMID- 8857884
TI  - Reduction in thigh muscle cross-sectional area and strength in a 4-year follow-up
      in late polio.
AB  - OBJECTIVE: To study changes in cross-sectional thigh muscle area and muscle
      strength in late polio subjects over a 4-year period. DESIGN: Longitudinal study
      of a cohort of polio survivors, comparing subjects who acknowledge (unstable)
      with those who do not acknowledge (stable) new muscle weakness. SETTING:
      University hospital. SUBJECTS: Eighteen subjects (6 men, 12 women) with polio
      myelitis sequelae (39 to 46 years of age) were studied on two occasions 4 years
      apart; the first examination was 37 to 44 years after onset of polio. Subjects
      were recruited through hospital registers, newspaper advertisement, and a patient
      organization. OUTCOME MEASUREMENTS: Thigh muscle and intermuscular and
      intramuscular adipose tissue (AT) cross-sectional areas were measured by computed
      tomography. Isometric muscle strength for knee extension and flexion was measured
      using a Kin-Com dynamometer. RESULTS: Cross-sectional muscle area decreased on
      average 1.3 +/- 3.6 cm2 (1.4%, p < .05); the intermuscular and intramuscular AT
      area increased 1.8 +/- 3.4 cm2 (12.1%, p < .05). When divided by legs in which
      subjects reported (unstable) or did not report (unstable) or did not report
      (stable) increased muscle weakness, unstable legs showed significant reduction (p
      < .05) in muscle area, whereas stable legs did not. Estimated total thigh muscle
      strength decreased 7.8% +/- 2.9% (p < .01), with a significant (p < .001)
      reduction in unstable legs (13.4% +/- 4.3%) but not in stable legs. The reduction
      in strength appears to be greater than the reduction in cross-sectional muscle
      area, but there is still a significant correlation (r = .44, p < .05).
      CONCLUSION: The present results demonstrate not only progress of muscle weakness,
      but also of muscle atrophy in postpolio subjects.

PMID- 8857885
TI  - Risk factors for death and emergency transfer in acute and subacute inpatient
      rehabilitation.
AB  - OBJECTIVES: To compare the risk of death or emergency transfer (ET) to an acute
      care hospital for acute and subacute rehabilitation inpatients, to identify risk
      factors, and to determine whether the risk factors vary by level of care. DESIGN:
      Proportional hazards regression analysis of retrospective cohort data.
      Explanatory variables included level of care, age, sex, medical stability at
      admission, and diagnosis. SETTING: An acute inpatient rehabilitation hospital and
      a skilled nursing facility-based subacute rehabilitation program. PATIENTS:
      Patients were selected from a database of all acute and subacute inpatients
      discharged between January 1992 and August 1994 (N = 4,755). Readmissions and
      pediatric patients were excluded (n = 896). Patients who had complete data (n =
      3,185) were included in the survival analysis; a separate univariable analysis
      was performed for patients who lacked complete data (n = 674). OUTCOME MEASURE:
      Rate of death or emergency transfer during rehabilitation. RESULTS: The overall
      risk was greater for subacute patients than for acute inpatients, 20.6% vs 11.6%,
      odds ratio = 2.0, CI = 1.6 to 2.5. The survival analysis indicated that age,
      level of care, sex, and stability were associated with the risk of death or
      emergency transfer (2.1 < or = zeta < or = 4.7; p < .05 for each). However, the
      difference in risk between subacute and acute care was greatest among younger
      patients. CONCLUSIONS: Careful consideration of risk factors is critical for
      proper assignment of patients to rehabilitation levels of care. However, research
      is needed to test these findings in other settings and to improve identification
      of high-risk patients.

PMID- 8857886
TI  - Reliability and validity of the FIM for persons aged 80 years and above from a
      multilevel continuing care retirement community.
AB  - OBJECTIVE: Development of accurate functional assessment instruments will help
      clinicians evaluate treatment outcome and plan realistic rehabilitation goals for
      elderly patients. The reliability, validity, and appropriateness of the
      Functional Independence Measure (FIM) were examined for a population aged 80
      years and more from a multilevel, continuing care retirement community. DESIGN:
      Forty-nine residents (average age 89.7 years, range 80 to 104 years; 46 women),
      were randomly selected. SETTING: Subjects were grouped according to their
      residence in either an Independent community (18 subjects), Sheltered Care (16
      subjects), or Skilled Nursing Facility (15 subjects). MEASUREMENTS: Subjects were
      evaluated twice using the FIM. Motor and cognitive scores were converted into
      interval measures (logits) using Rasch Analysis with the BIGSTEPS statistical
      package. Parametric statistical procedures were utilized to further analyze data.
      RESULTS: FIM motor and cognitive items formed 2 unidimensional and linear
      subscales. Hierarchical levels of FIM item difficulties were identified. Bladder
      management, bowel management, and grooming were misfitting motor items. Memory
      misfit for the cognitive subscale. High test-retest reliability for 45 repeated
      FIM assessments for the motor, (ICC = .9) and cognitive subscales (ICC = .8) was
      demonstrated. One way ANOVA for FIM ratings for the 3 groups demonstrated
      significant differences for both the motor subscale, F(2,46) = 34.71, p < .05,
      and the cognitive subscales, F(2,46) = 12.42, p < .05. CONCLUSION: Construct
      validity of the FIM was demonstrated. High test-retest reliability was
      demonstrated. Environmental context and operational definitions influenced FIM
      ratings. Subjects' FIM ratings, abilities, and time to complete the locomotor
      walking item correlated with their current residence in increasingly dependent
      environments. These findings suggest that with certain caveats, the FIM may be
      useful as a functional assessment instrument for persons who are 80 or more years
      old.

PMID- 8857887
TI  - Motor fitness in children and adolescents with traumatic brain injury.
AB  - OBJECTIVE: This study examined the test-retest reliability of selected motor
      fitness test items among children with severe traumatic brain injury. DESIGN: A
      cohort study consisting of two testing session, one week apart. SETTING: All
      subjects were recruited from among the former clients of a pediatric
      rehabilitation center. SUBJECTS: A convenience sample of 19 subjects, 13 boys and
      6 girls aged 8 to 17 years, volunteered to participate. All participants had a
      diagnosis of a severe traumatic brain injury (X +/- SD = 5.88 +/- 1.71 on the
      Glascow Coma Scale), had completed a program of physical rehabilitation, and were
      evaluated at 4.16 +/- 2.61 years after their injury. MAIN OUTCOME MEASURES:
      Performance on twelve motor fitness test items (including flexibility, agility,
      muscular strength, cardiorespiratory endurance, power, muscular endurance, and
      coordination) was measured at each of two structured evaluation sessions.
      RESULTS: No differences (t tests, p < or = .05) were found between the
      performances on the two testing sessions for any of the variables. The test
      retest reliability was established via the intraclass correlation (ICC) and
      ranged from .84 to .98, indicating "almost perfect" agreement. CONCLUSION: The
      data indicate that these motor fitness testing protocols are reliable and
      applicable to traumatic brain injured children in a clinical setting and can thus
      be used by therapists to plan future interventions to improve the fitness of this
      clientele.

PMID- 8857888
TI  - Stroke rehabilitation: are highly structured units more conducive to physical
      activity than less structured units?
AB  - OBJECTIVE: To determine if the physical design and organizational structure of
      rehabilitation units is related to the amount of patients' motor activity.
      DESIGN: An observational study was conducted; time samples of the motor activity
      of patients following stroke were taken between 7AM and 7PM both on weekdays and
      weekends. SETTING: Two rehabilitation units associated with general hospitals
      with different physical design and organizational structure. One unit was spread
      over a large area and had a highly organized daily structure; the other was small
      and informally organized. SUBJECTS: Inpatients with hemiplegia as a result of
      stroke who gave consent to participate. MAIN OUTCOME MEASURE: The nature and
      frequency of 14 motor activities were compared between units. RESULTS: No
      significant difference was found in any of the observed motor activities between
      the units when using independent groups t tests (p = 0.1-0.8). Subjects in both
      units spent more than 70% of their day in activities largely unrelated to
      physical outcome (eg, conversing with visitors or doing nothing observable) and
      less than 20% of the day in activities that could potentially contribute to their
      recovery (eg, in therapy or exercising independently). CONCLUSIONS:
      Rehabilitation units are not functioning as learning environments. The challenge
      is to identify and implement measures that will change this finding.

PMID- 8857889
TI  - Changes in spine height throughout 32 hours of bedrest.
AB  - OBJECTIVE: To examine the changes in length of the spine during prolonged
      bedrest. DESIGN: The height of subjects was recorded over two control days and
      subsequently during the course of 32 hours of bedrest. SETTING: Data were
      collected in a student dormitory. PARTICIPANTS: Eight male volunteers from an
      undergraduate student population. RESULTS: Subjects lost approximately 10mm in
      spine height over the course of each of two control days. When they remained in
      bed after a usual night's rest, their spine height did not increase further. Even
      after 32 hours of continuous bedrest, the spine did not increase its length
      beyond the normal morning height. CONCLUSIONS: Bedrest does not allow normal
      expulsion of fluids from the disc leading to higher stresses associated with
      fully imbibed discs.

PMID- 8857890
TI  - Deficit and change in gait velocity during rehabilitation after stroke.
AB  - OBJECTIVE: To quantify the initial deficit, change, and outcome in gait velocity
      during inpatient rehabilitation following stroke. DESIGN: The initial deficit on
      admission to rehabilitation was quantified by comparing 42 stroke patients with
      42 controls matched by gender and age. The change in the stroke patients during
      the next 8 weeks was quantified and gait outcome was compared with functional and
      normal criteria. SETTING: Patients were referred from four inpatient
      rehabilitation centers at the time of admission following a median of 16.5 days
      in the acute hospital. PATIENTS:  SELECTION CRITERIA: ability to give informed
      consent; unilateral first stroke; ability to walk 10 meters. INTERVENTION:
      Patients participated in a median of 17.38 hours of individual physical therapy
      including a median of 6.92 hours of gait training during the 8 weeks. MAIN
      OUTCOME MEASURE: Gait velocity. RESULTS: Gait velocity was initially 38.6%
      (26.7m/min SD = 14.9) of the performance of controls and improved to 55.1%
      (38.1m/min). At outcome only 24% exceeded the 5th percentile of controls
      (48.1m/min) or the velocity required to cross the typical signalled intersection
      (46.2m/min). The change was only 26% of the initial deficit. Fifty-five percent
      of the patients improved beyond the 95% confidence intervals surrounding the
      error of measuring change. Indices of responsiveness indicated that there was a
      high signal-to-noise ratio and a robust effect size. CONCLUSION: Gait velocity
      discriminated the effect of stroke and the change during rehabilitation.

PMID- 8857891
TI  - Functional outcome measures to assess interventions for spasticity.
AB  - PURPOSE: Clinicians use functional loss as a criterion to treat spasticity, but
      the connection between function and severity of spasticity is not well
      established for monitoring spasticity treatment effect. Studies were reviewed
      which have implemented outcome measures to assess functional changes relative to
      changes in spasticity. Criteria for review included the reliability and internal
      validity of the functional measures used and the strengths/weaknesses of the
      study designs that likely affected the external validity of the measures for this
      application. Guidelines are provided for the use and development of functional
      outcome measures in futures studies of spasticity treatment based on this review.
      DATA IDENTIFICATION: An English-language literature search using MEDLINE and
      bibliographies of published articles and textbooks was conducted. RESULTS: Very
      few functional measures demonstrated changes concurrent to a reduction in
      spasticity. There were multiple potential confounding factors in study protocols,
      reporting of results, and data analysis that might account for the limited number
      of measures shown to be valid for this application. Selected standardized ordinal
      functional outcome scales (the PECS and PEDI) and specific functional tasks were
      identified as measures that show promise for assessing changes concurrent with
      altered spasticity level. CONCLUSION: Based on a review of previous studies,
      functional measures involving posture, positioning, balance, and certain mobility
      skills have potential, with further test development, to provide needed
      information regarding the impact of spasticity on functional outcome.

PMID- 8857892
TI  - Lower extremity amputation secondary to heparin-associated thrombocytopenia with
      thrombosis.
AB  - A rare cause of limb amputation is heparin-associated thrombocytopenia with
      thrombosis (HATT). There have been no case reports in the rehabilitation
      literature of lower extremity amputation secondary to HATT. Three case reports
      are presented to illustrate how HATT can develop and cause limb ischemia with
      subsequent amputation. HATT occurs in less than 1% of patients receiving heparin,
      has an immunological basis for its etiology, and is diagnosed both clinically and
      with laboratory confirmation. In addition, there are various treatment options,
      with the most fundamental being cessation of heparin therapy. HATT does present
      in the rehabilitation setting and physiatrists should be prepared to diagnose and
      manage it effectively.

PMID- 8857893
TI  - Cisapride as a treatment for gastroparesis in traumatic brain injury.
AB  - Gastroparesis is a well-documented finding among patients with severe traumatic
      brain injuries. The treatment of choice has been metoclopramide, but it is less
      than ideal given its central dopaminergic blocking activity. Cisapride is a newer
      prokinetic agent without side effects on the central nervous system and might be
      a superior treatment. The case of a healthy 22-year-old man who suffered a severe
      traumatic brain injury and multiple trauma in a motor vehicle accident is
      reported. The patient required gastrostomy tube placement but developed recurrent
      aspiration pneumonia once feedings were initiated. Despite receiving
      metoclopramide, barium studies revealed gastroparesis, a significant decrease in
      gastric peristalsis, and reflux. A jejunostomy tube was placed to prevent further
      aspiration. The administration of cisapride was begun, and 2 days later the
      patient was changed back to G-tube feedings with no evidence of residual
      aspirates. Repeat barium study showed definite improvement in peristalsis. This
      case demonstrates the potential usefulness of cisapride in patients with
      traumatic brain injury. Although further research is necessary, efficacy without
      central dopamine blockage may make cisapride the treatment of choice for
      gastroparesis and reflux in traumatic brain injury.

PMID- 8857894
TI  - A national treasure. The 82nd Clinical Congress of the American College of
      Surgeons.

PMID- 8857895
TI  - The diagnosis and treatment of gastroesophageal reflux disease in a managed care
      environment. A surgeon's response.

PMID- 8857896
TI  - Managed care and the community surgeon.
AB  - Managed care is rapidly spreading in the United States. Although it has led to
      reduced costs, the patient-physician relationship has been negatively affected.
      Managed care has an impact on patient care, student learning, and residency
      training. Physicians must act together to maintain a quality medical care system
      in this country.

PMID- 8857897
TI  - The shift toward a managed care environment in a multispecialty group practice
      model. Looking for reciprocal benefits.
AB  - Managed care is notably affecting the practice of surgery in the United States.
      Four principal elements are subject to change: (1) patient care patterns, (2)
      ethics, (3) education and research, and (4) surgeon compensation. The Virginia
      Mason Clinic, a multispecialty group practice, is adapting to the demands of
      managed and capitated care. With the patient as the primary focus of effort, the
      goal is to create optimum value in health care. The principles of Continuous
      Quality Improvement are used to increase value in health care by ensuring
      appropriate treatment with optimum outcome at reasonable cost. Practice patterns
      are shifting to provide value to patients and payers. Ethical conflicts threaten
      but have been avoided. Surgical education remains unaffected, but future funding
      is problematic. The emphasis in surgical research has shifted toward outcome
      based studies. The conflict between work effort and resource conservation as
      determinants of physician compensation is less for surgical than for medical
      practitioners. Although the principal benefactors of the shift toward managed
      care have been the payers, patients have gained modestly through efficiencies in
      the health care process and more stable insurance premiums. The satisfaction
      level of the surgeons in our multispecialty group practice remains high. Surgical
      research is thriving, volumes and case mix remain excellent, and changes in
      practice pattern have enabled us to increase efficiency without compromising
      patient care.

PMID- 8857898
TI  - The myths of managed care. Surgical perspectives.
AB  - Managed care is the contemporary and near-future system of medicine in which we
      must learn to exist. Many are afraid of managed care only because they are not
      familiar with the concept. Misconceptions abound in the medical community
      concerning the sudden rise of managed care systems. Surgeons, their postgraduate
      training and experience, daily practice, multiple outside interests, and future
      governance of their craft are not at risk in the managed care environment.

PMID- 8857899
TI  - Combined preoperative irradiation and local hyperthermia delays early healing of
      experimental colonic anastomoses.
AB  - OBJECTIVE: To determine if a combination of preoperative irradiation and local
      hyperthermia of a colonic segment is detrimental to subsequent early anastomotic
      healing. DESIGN: A prospective randomized experimental trial. SETTING: An animal
      research laboratory. INTERVENTIONS: Eighty male Wistar rats were randomly divided
      into 4 groups. In each animal, a segment of the colon was treated successively by
      (sham) irradiation and (sham) hyperthermia. After 5 days, a colonic resection was
      performed and an anastomosis was constructed; the distal limb consisted of (sham)
      irradiated, (sham) hyperthermia-treated bowel. The rats were killed 3 or 7 days
      after surgery. MAIN OUTCOME MEASURES: Body weight, serum albumin and protein
      levels, anastomotic bursting pressure, breaking strength, and hydroxyproline
      content. RESULTS: All animals tolerated (sham) treatment well. Weight was
      diminished, though not notably, in treated animals vs the control group. After
      combined preoperative irradiation and hyperthermia, the frequency of local
      anastomotic complications increased: 4 of 20 animals had a covered perforation
      when they were killed. In this group, the bursting pressure was lower 3 days
      after the operation (P = .008). The breaking strength was also lower but not
      notably. The serum albumin level was significantly lower in this group vs the
      control group (P = .006); the serum protein level was not decreased. After 7
      days, no differences existed between the groups. The hydroxyproline content of
      the anastomotic tissue was notably higher in rats treated with radiation plus
      hyperthermia vs control rats (in both the 3- and 7-day groups). The anastomotic
      hydroxyproline concentration did not differ between the groups. CONCLUSIONS: The
      combination of preoperative irradiation and hyperthermia results in increased
      local anastomotic complications. Anastomotic strength is at risk in the first
      days after the anastomotic reconstruction. Preoperative irradiation or
      hyperthermia alone does not lead to impaired anastomotic healing in the early
      phase.

PMID- 8857900
TI  - Refeeding hypophosphatemia in critically ill patients in an intensive care unit.
      A prospective study.
AB  - BACKGROUND: Hypophosphatemia has been reported after refeeding of malnourished
      patients. Nutritional support is often delayed in patients in the intensive care
      unit (ICU) as a consequence of enteral intolerance and bowel hypomotility.
      OBJECTIVE: To determine the incidence, risk factors, and clinical impact of
      refeeding hypophosphatemia in a heterogeneous group of patients in an ICU.
      DESIGN: Prospective, noninterventional study. SETTINGS: Surgical and medical ICUs
      of a university-affiliated community hospital. PATIENTS: Sixty-two patients in
      the ICU who were refed after being starved for at least 48 hours were
      prospectively followed up. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Each
      patient had a nutritional assessment prior to the initiation of nutritional
      support. Serum phosphate, magnesium, and calcium levels were measured at
      baseline, and these measurements were repeated daily. Refeeding hypophosphatemia
      was considered to have developed in patients whose serum phosphorus level fell by
      more than 0.16 mmol/L to below 0.65 mmol/L. RESULTS: Twenty-one patients (34%)
      experienced refeeding hypophosphatemia. In 6 patients, the serum phosphorus level
      fell below 0.32 mmol/L. The only risk factor studied that could predict the
      development of hypophosphatemia was the serum prealbumin concentration (mean +/-
      SD, 127 +/- 34 vs 79 +/- 40 g/L, P < .001). Seventeen (81%) of these 21 patients
      in whom hypophosphatemia developed had a prealbumin concentration less than 110
      g/L compared with that in 12 (30%) of the patients who did not experience this
      complication (P < .001). In those patients in whom refeeding hypophosphatemia
      developed, the serum phosphorus level reached a mean +/- SD nadir of 1.9 +/- 1.1
      days after feeding was started. Although the Acute Physiology and Chronic Health
      Evaluation II score was similar (mean +/- SD, 19 +/- 6 vs 18 +/- 7), the length
      of mechanical ventilation (mean +/- SD, 10.5 +/- 5.2 vs 7.1 +/- 2.8 days; P =
      .04) and the length of hospital stay (mean +/- SD, 12.1 +/- 7.1 vs 8.2 +/- 4.6
      days; P = .01) were significantly longer in those patients who experienced
      hypophosphatemia compared with those patients who did not experience this
      complication. CONCLUSIONS: Refeeding hypophosphatemia occurs commonly in
      critically ill patients in the ICU. Starvation for a period as short as 48 hours
      and poor nutritional status predispose to this syndrome. Patients at risk should
      be refed slowly, and the serum phosphorus level should be closely monitored and
      supplemented as required.

PMID- 8857901
TI  - Secondary hyperparathyroidism following biliopancreatic diversion.
AB  - OBJECTIVE: To investigate the cause of osteomalacia following biliopancreatic
      diversion(BPD) surgery for obesity. DESIGN: A retrospective, case-comparison
      study. SETTING: A tertiary care center. PATIENTS: A case group of 12 subjects
      (including 9 women; mean age +/- SEM, 48.5 +/- 3.0 years; mean preoperative body
      mass index +/- SEM, 43.7 +/- 2.3 kg/m2, and mean weight loss +/- SEM, 75 +/- 14
      kg) who have undergone BPD (referred to as BPD group hereafter) and a comparison
      group of 10 subjects (including 9 women; mean age +/- SEM, 49.6 +/- 3.3 years;
      mean preoperative body mass index +/- SEM, 44.0 +/- 2.5 kg/m2; and mean weight
      loss +/- SEM, 55 +/- 15 kg) following vertical banded gastroplasty (VBG)
      (referred to as VBG group hereafter). MAIN OUTCOME MEASURES: Serum and urine
      markers for bone metabolism. RESULTS: Compared with the VBG group, the BPD group
      had significantly lower concentrations of the following components: serum calcium
      (2.14 +/- 0.05 mmol/L vs 2.37 +/- 0.05 mmol/L [8.6 +/- 0.2 mg/dL vs 9.5 +/- 0.2
      mg/dL]), serum 25-hydroxyvitamin D (24 +/- 6 nmol/L vs 64 +/- 6 nmol/L), urine
      calcium excretion (1.7 +/- 0.7 mmol/d vs 4.5 +/- 0.7 mmol/d [68 +/- 28 mg/d vs
      180 +/- 28 mg/d]), and serum carotene (0.40 +/- 0.15 mmol/L vs 1.29 +/- 0.16
      mmol/L). The BPD group had significantly higher concentrations of the following
      components: serum parathyroid hormone (13.6 +/- 2.1 pmol/L vs 5.2 +/- 2.3
      pmol/L), serum alkaline phosphatase (139 +/- 8 U/L vs 86 +/- 9 U/L), and urinary
      hydroxyproline/creatine (52 +/- 5 mumol/mmol vs 19 +/- 5 mumol/mmol). CONCLUSION:
      These data suggest that following BPD, secondary hyperparathyroidism attributed
      to hypocalcemia results from malabsorption of vitamin D. However, we cannot
      exclude the possibility of concurrent calcium malabsorption with vitamin D
      malabsorption.

PMID- 8857902
TI  - Pancreas graft loss caused by intra-abdominal infection. A risk factor for a
      subsequent pancreas retransplantation.
AB  - OBJECTIVE: To investigate whether previous pancreas graft loss caused by intra
      abdominal infection is a risk factor for a subsequent pancreas retransplantation.
      DESIGN: Retrospective case-series analysis. SETTING: Large university hospital.
      PATIENTS: Of 97 pancreatic retransplantations (July 1, 1985 to June 30, 1994), 13
      (13%) were performed after previous pancreas grafts had been lost because of
      intra-abdominal infection. MAIN OUTCOME MEASURES: Cause of retransplant graft
      loss; patient survival. RESULTS: Of 13 cases of pancreatic retransplantations
      performed after previous grafts had been lost because of intra-abdominal
      infection, 12 (92%) were again complicated by intra-abdominal infection. Of these
      12 retransplantation infections, 10 were caused by the same microbial species
      that had caused failure of the previous graft 1 to 5 years earlier (8 required
      graft pancreatectomy [mortality rate, 25%], and 2 were successfully treated) and
      2 were caused by different microbial species (both required graft pancreatectomy
      [mortality rate, 0%]). In 1 of the 13 retransplantations, prophylactic
      antimicrobial treatment was directed at the microbial species that had caused
      failure of the previous graft; no recurrent intra-abdominal infection developed.
      CONCLUSIONS: Intra-abdominal infection after a previous pancreas transplantation
      is a risk factor for recurrence of infection by the same microbial species after
      a subsequent retransplantation. For the selected patients who are considered for
      retransplantation in spite of their previous graft loss caused by intra-abdominal
      infection, periretransplantation antimicrobial prophylaxis should include a
      prolonged course of an agent directed against the previously identified microbial
      species.

PMID- 8857903
TI  - Surgical Infection Society position on vancomycin-resistant Enterococcus.
AB  - The risk of transfer of vancomycin resistance to staphylococci is a real
      possibility and has been achieved in the laboratory. Prolonged colonization
      occurs with vancomycin-resistant Enterococcus (VRE), and many more patients are
      colonized than infected. The failure to identify, isolate, and adhere to
      infection control measures when caring for VRE-colonized patients dooms to
      failure any means to control its spread. Control of vancomycin use alone is
      unlikely to greatly affect the number of patients at risk for VRE colonization.
      The global spread of VRE may be impossible to stop, but infection control
      measures are the most important line of defense inside hospitals.

PMID- 8857904
TI  - Low-dose heparin thromboembolism prophylaxis.
AB  - OBJECTIVE: To determine a rational approach to heparin dosing for thromboembolism
      prophylaxis. DESIGN: Literature review. RESULTS: Three commonly used heparin
      dosing regimens were identified: (1) standard low-dose heparin (5000 U
      administered subcutaneously 2-3 times per day); (2) adjusted-dose heparin
      (adequate to elevate the activated partial thromboplastin time to 5 seconds above
      the upper limit of normal); and (3) low-molecular-weight heparin (30 mg
      subcutaneously twice daily without monitoring). CONCLUSIONS: Adjusted-dose
      heparin thromboembolism prophylaxis is both the safest and most reliable method
      currently available.

PMID- 8857905
TI  - Ambulatory parathyroidectomy for primary hyperparathyroidism.
AB  - OBJECTIVE: To evaluate whether the combined application of preoperative
      localization and intraoperative monitoring of intact parathyroid hormone (iPTH)
      levels could facilitate safe outpatient parathyroidectomy. DESIGN: Consecutive
      patients, who had no antecedent social or medical conditions mandating
      hospitalization, were prospectively offered ambulatory parathyroidectomy with a
      mean follow-up of 7 months (range, 1-25 months). SETTING: Tertiary care referral
      center PATIENTS: From 85 patients who had primary hyperparathyroidism with
      hypercalcemia and elevated iPTH levels, 57 were offered outpatient
      parathyroidectomy. Nineteen patients were asymptomatic, 3 had hypercalcemic
      crisis, and the others gave a history of renal stones or had complaints
      consistent with bone disease. INTERVENTIONS: Technetium Tc 99m sestamibi
      scintiscans were used for preoperative localization. Monitoring iPTH levels
      during parathyroidectomy quantitatively assured the surgeon (G.L.I. only) when
      all hyperfunctioning glands were excised. MAIN OUTCOME MEASURE: The number of
      patients without complications and with short operative times who were discharged
      without hospital admission or overnight stay. RESULTS: The combination of
      preoperative localization of abnormal parathyroid glands and a decline in
      circulating iPTH levels predicting postoperative normocalcemia after excision of
      all hyperfunctioning glands resulted in successful parathyroidectomy in 84 of 85
      patients. A decreased operative time (average, 52 minutes) with minimal neck
      dissection permitted outpatient parathyroidectomy in 42 of 57 eligible patients.
      CONCLUSIONS: The combination of preoperative parathyroid scintiscan localization
      and iPTH level monitoring during surgery permitted successful parathyroidectomy
      in an ambulatory setting in half of a consecutive series of patients with primary
      hyperparathyroidism. The safety, success, and likely cost savings of this
      approach suggest wider application.

PMID- 8857906
TI  - Reduced inflammatory response in minimal invasive surgery of pneumothorax.
AB  - OBJECTIVE: To elucidate whether thoracoscopy for surgical therapy of pneumothorax
      leads to a reduction of inflammatory responses in comparison with standard
      thoracotomy. DESIGN: A prospective randomized study PATIENTS: Eleven patients (9
      men and 2 women; median age, 28 years; range, 21-44 years) were treated by
      thoracotomy; 10 patients (9 men and 1 woman; median age, 26 years; range, 21-28
      years) were managed thoracoscopically. The plasma concentrations of the following
      were determined: polymorphonuclear granulocyte elastase and C-reactive protein as
      inflammatory parameters and prostanoids (prostacyclin, thromboxane A2,
      prostaglandin F2 alpha, prostaglandin M, and prostaglandin E2) as vasoactive
      parameters. Blood sampling was performed perioperatively and on day 3 after
      surgery. RESULTS: The thoracoscopy group revealed a shorter hospital stay (5 vs 7
      days; P < .05) and a significantly reduced need for intravenous pain medication
      within 48 hours (1 vs 3 requirements; P < .01) vs the thoracotomy group. The
      release of inflammatory (C-reactive protein, P < .01) and vasoactive
      (prostacyclin and thromboxane A2, P < .01) mediators was less during thoracoscopy
      compared with standard thoracotomy. CONCLUSIONS: The thoracoscopic procedure is
      less invasive when performing wedge resection of apical blebs. With intracavitary
      management being equivalent to the conventional technique, the curtailed
      morbidity after thoracoscopic surgery is considered to be related to the minimal
      trauma associated with the access to lung tissue and the reduced handling of lung
      tissue.

PMID- 8857907
TI  - Risk of recurrent biliary tract disease after cholecystectomy in patients with
      duodenal diverticula.
AB  - OBJECTIVE: To determine if the presence of duodenal diverticula predisposes to
      the development of common bile duct stones. DESIGN: Cohort study; median follow
      up, 10.0 years (25th and 75th percentiles, 5.2 and 16.1 years, respectively).
      SETTING: Tertiary care center. PATIENTS: One hundred fifty-seven patients with
      radiologically diagnosed duodenal diverticula who had undergone cholecystectomy
      from 1950 through 1987 and were asymptomatic at the initiation of follow-up. MAIN
      OUTCOME MEASURES: All patients were followed up for evidence of recurrent biliary
      tract disease to the following end points: (1) evidence of choledocholithiasis
      demonstrated by radiologic surgical, or biochemical means and (2) clinical or
      biochemical evidence of biliary pancreatitis. RESULTS: Of the 157 patients in the
      study cohort, 13 patients were categorized as having had recurrent biliary tract
      disease. Using the Kaplan-Meier survivorship method, the cumulative probabilities
      of recurrent biliary tract disease in patients with radiologically diagnosed
      duodenal diverticula were 3.6% at 5 years (95% confidence interval, 0.5-6.9),
      5.5% at 10 years (95% confidence interval, 1.5-9.4), and 10.2% at 15 years (95%
      confidence interval, 3.8-16.7). Age, common bile duct exploration and
      choledochotomy, and the presence of common bile duct dilatation were not found to
      be significantly associated with recurrence based on a univariate analysis of
      risk factors by means of the log-rank statistic. CONCLUSIONS: For patients with
      radiologically diagnosed, second-portion duodenal diverticula, the risk of
      developing recurrent bile duct stones after cholecystectomy is lower than has
      been suggested in previous studies. In the absence of concurrent
      choledocholithiasis, sphincterotomy or biliary bypass at the time of
      cholecystectomy seems unwarranted.

PMID- 8857908
TI  - Local irrigation with tissue factor pathway inhibitor inhibits intimal
      hyperplasia induced by arterial interventions.
AB  - OBJECTIVE: To evaluate the capacity of local irrigation with tissue factor
      pathway inhibitor (TFPI) to inhibit vessels from neointimal lesion formation
      following intimectomy or balloon angioplasty. DESIGN: The common carotid arteries
      in New Zealand white rabbits were subjected to either intimectomy or balloon
      angioplasty. INTERVENTION: Before restoring blood flow, the lumina of the vessels
      were irrigated with 1 mL of Dulbecco phosphate-buffered saline either with TFPI
      (100 micrograms/mL [TFPI group, n = 10]) or without TFPI (control group, n = 10).
      MAIN OUTCOME MEASURES: The area of neointimal formation and the ratio of the
      intimal to medial areas (I/M) were determined from elastin-stained sections.
      RESULTS: The area of neointima and the I/M ratio were not significantly different
      at 2 weeks postoperatively. However, at 4 weeks, TFPI-treated vessels
      demonstrated a significant reduction in the neointimal lesion and the I/M ratio
      compared with those of controls, following both angioplasty and intimectomy.
      Transmission electron microscopy showed a lack of platelet aggregation and
      thrombus formation at the intimal surface in the TFPI-treated vessels.
      CONCLUSIONS: Local irrigation with TFPI at the time of arterial interventional
      therapy inhibits intimal hyperplasia following either balloon angioplasty or
      intimectomy. We hypothesize that TFPI binds to the injured vessel surface and
      inhibits the cascade of thrombotic events that promote intimal hyperplasia.

PMID- 8857909
TI  - Endoscopic sympathectomy treatment for craniofacial hyperhidrosis.
AB  - OBJECTIVE: To present endoscopic T-2 sympathectomy as a minimally invasive
      therapy for craniofacial hyperhidrosis (CH). DESIGN: Follow-up study of 30
      patients with CH treated by the new method in a 4-year period. The duration of
      follow-up was from 8 to 44 months (mean, 15 months). SETTING: University
      hospital. PATIENTS: Thirty consecutive patients with CH (18 men, 12 women)
      treated by the new method. All patients were essentially in good health except
      that they suffered from distressing CH to the extent that their daily activities
      were often disturbed. Their ages ranged from 7 to 63 years (mean age, 42.8
      years). INTERVENTION: Endoscopic sympathectomy on both sides was carried out in a
      1-stage operation for all patients. MAIN OUTCOME MEASURES: The patients were
      interviewed 1 week and then 3 months after surgery and then followed up by
      telephone interview about the alleviation or recurrence of CH and complications.
      RESULTS: All of the treated patients obtained a satisfactory alleviation of CH.
      One case was complicated by a mild and transient ptosis of the left eye. No
      recurrence of CH was noticed during the follow-up period. CONCLUSIONS: This
      therapeutic procedure is minimally invasive and effective. It causes minimal
      discomfort and was associated with no major complications in this series. The
      patients require only an overnight hospital stay and the operation scars are
      small. Endoscopic sympathectomy has proven to be an effective method in treating
      patients with distressing CH.

PMID- 8857910
TI  - Usefulness of ultrasound-guided, fine-needle aspiration biopsy for palpable
      breast tumors.
AB  - OBJECTIVE: To investigate whether ultrasound (US) guidance improves the
      sensitivity of fine-needle aspiration biopsy (FNAB) in patients with palpable
      breast tumors. DESIGN: A retrospective study. SETTING: A university hospital.
      PATIENTS: A total of 107 patients with breast tumors (114 lesions) underwent US
      guided FNAB and 138 patients (143 lesions) underwent FNAB guided by palpation
      (standard FNAB). MAIN OUTCOME MEASURES: The diagnoses obtained by FNAB were
      compared with the surgical findings and the diagnostic value of US-guided FNAB
      was evaluated. RESULTS: The sensitivity of US-guided FNAB was 89.3%, the
      specificity was 82.9%, and the accuracy was 86.9%. In contrast, the sensitivity
      of standard FNAB was 61.1%, the specificity was 73.3%, and the accuracy was
      65.0%. For breast tumors 2.0 cm or less in diameter, the sensitivity and accuracy
      of US-guided FNAB were significantly higher than those of standard FNAB.
      CONCLUSION: Ultrasound-guided FNAB can improve the preoperative diagnosis of
      breast cancer, especially in patients with tumors that are 2 cm or less in
      diameter.

PMID- 8857911
TI  - Prognostic value of the monoethylglycinexylidide liver function test in assessing
      donor liver suitability.
AB  - BACKGROUND: Liver graft assessment prior to transplantation continues to be
      controversial. Various donor organ parameters must be evaluated to ensure that
      the transplanted organ will function and that the number of organs discarded will
      be minimized. Recent attempts to quantify liver function have utilized the
      metabolism of lidocaine to monoethylglycinexylidide (MEGX), and the MEGX test has
      been employed to evaluate the functional characteristics of donor livers prior to
      transplantation, with conflicting results. OBJECTIVE: To ascertain the role of
      quantitating the metabolic rate of lidocaine in predicting the results of liver
      transplantation. METHODS: Consecutive liver donors (N = 37) underwent
      quantitation of the amount of lidocaine converted to MEGX at 15 minutes. The
      donor patients were divided arbitrarily into efficient and poor lidocaine
      metabolizers, and the results of liver transplantation were evaluated. RESULTS:
      Patients who received livers that produced MEGX values of 80 ng/mL or less in 15
      minutes had no definable alteration in transplantation outcome compared with
      patients who received livers that were more efficient lidocaine metabolizers. In
      a collected series, 46 patients who received livers that produced MEGX values of
      80 ng/mL or less had a 1-month graft survival rate of 89% (41/46), while 74
      patients who received livers that produced MEGX values greater than 80 ng/mL had
      a 1-month graft survival rate of 86% (64/74). CONCLUSIONS: The MEGX test had no
      practical utility in predicting liver graft functional status.

PMID- 8857912
TI  - Vascular reconstruction for limb salvage in sarcoma of the lower extremity.
AB  - OBJECTIVES: To examine the patency and limb-salvage characteristics of vascular
      reconstruction in patients with sarcomas of the lower extremity who had been
      treated with limb-preserving resection and to examine patient survival during a
      long follow-up period. DESIGN: Retrospective cohort study. SETTING: University
      hospital, tertiary referral center. PATIENTS: From 1984 to 1992, 14 patients
      underwent limb-preserving resection of sarcomas in the proximal lower extremity,
      with 20 vascular reconstructions performed. OUTCOME MEASURES: Color Doppler scans
      documented patency of the vascular reconstructions. Clinical evaluation included
      functional results in terms of limb movement and quality of life. Local tumor
      control and systemic recurrence were examined by repeated radiologic examination.
      Overall survival as well as time and cause of death were assessed. RESULTS: A
      total of 13 patients had patent vascular grafts, while the venous graft became
      occluded in 1 patient. Limb function was rated as excellent or good in 9
      patients, as fair in 3, as poor in 1, and could not be clinically estimated in 1.
      Postoperative thrombosis of the venous graft was detected in 3 patients and was
      effectively managed by thrombectomy in 2. Three patients underwent reoperation
      because of hematoma or complications caused by local infection. The tumor
      endoprosthesis had to be replaced in 3 patients. During follow-up periods that
      ranged from 15 to 132 months (mean, 55 months), 4 patients died. In all of these
      patients the cause of death was systemic recurrence in the lung. Two additional
      patients developed pulmonary metastases, but at the time of this report, they
      were still alive as long as 132 months after operative resection or chemotherapy.
      No local recurrence was found. CONCLUSION: Limb-preserving resection of sarcoma
      of the lower extremity can be performed with satisfactory function of the limb
      maintained, even if it becomes necessary to resect the femoral vessels.
      Autologous venous graft for vascular reconstruction is the treatment of choice.
      In spite of the high incidence of metastases, considerable long-term survival is
      possible.

PMID- 8857913
TI  - Primary adenocarcinoma of the angle of Treitz. Case report and review of the
      literature.
AB  - We describe a 54-year-old man who was referred with the diagnosis of
      adenocarcinoma of the angle of Treitz and treated with the use of a
      duodenojejunal segmentary resection. After a review of the literature, we
      emphasize the difficulty of making an early diagnosis and discuss the most
      appropriate surgical treatment of tumors of the angle of Treitz. The better
      prognosis of these neoplasms compared with those of the proximal duodenum can be
      supported by some embryological findings observed from a different research
      project currently in progress.

PMID- 8857914
TI  - A rare complication of splenic artery aneurysm: mesenteric steal syndrome.

PMID- 8857915
TI  - Changes in intracranial pressure associated with apneumic retractors.

PMID- 8857916
TI  - Hormone replacement therapy lowers plasma Lp(a) concentrations. Comparison of
      cyclic transdermal and continuous estrogen-progestin regimens.
AB  - To study the responses of serum lipoproteins, apoproteins (apo's), and
      lipoprotein(a) (Lp[a]) to two frequently used hormone replacement therapies
      (HRTs), 120 postmenopausal women were randomly allocated to receive either
      transdermal therapy consisting of 28-day cycles with patches that delivered 17
      beta-estradiol (50 micrograms/d) combined with cyclic oral medroxyprogesterone
      acetate (10 mg/d for 12 days per cycle) or continuous oral 17 beta-estradiol (2
      mg/d) together with norethisterone acetate (1 mg/d) for 12 months. Blood samples
      were taken before and at 6 and 12 months of HRT. Concentrations of serum total,
      low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol
      decreased by 14% (P < .001), 17% (P < .001), and 9% (P < .001) in the oral HRT
      group. Respective changes were 5.7% (P < .001), 4.8% (P < .05), and 4.7% (NS) in
      the transdermal group. Serum triglycerides remained unchanged in the oral group
      but decreased by 15.7% (P < .001) in the transdermal group. We observed only
      trivial changes in serum apo B levels. The changes in apo A-I levels paralleled
      those of HDL cholesterol in the oral HRT group. The concentration of serum Lp(a)
      decreased by 31% (P < .001) and 16% (P < .001) in the two groups. The combination
      of progestin and transdermal estrogen was not associated with any further change
      of Lp(a). The decrement in Lp(a) during therapy was positively associated with
      baseline Lp(a) levels in both groups (r = .96, P < .001 and r = .88, P < .001).
      Thus, both HRT regimens were highly effective in lowering elevated Lp(a) levels
      in postmenopausal women. The divergent responses of LDL and HDL cholesterol in
      the two HRT groups may influence the potential cardioprotective effects of the
      two HRT regimens. Prospective trials are needed to define the long-term effects
      with respect to coronary heart disease risk.

PMID- 8857917
TI  - Dietary cholesterol feeding suppresses human cholesterol synthesis measured by
      deuterium incorporation and urinary mevalonic acid levels.
AB  - The objective of this study was to measure the response of cholesterol
      biosynthesis in subjects to three different amounts of dietary cholesterol: 50
      (low), 350 (medium), and 650 (high) mg cholesterol per 2800 kcal. Individuals
      with low (n = 7), normal (n = 12), and elevated (n = 11) plasma cholesterol
      concentrations consumed in random order solid-food test diets (15%, 55%, and 30%
      of energy as protein, carbohydrate, and fat, respectively) at each dietary
      cholesterol level. The three diets were consumed for 4 weeks each, and each
      dietary phase was separated by a 4-week washout period. During the final week of
      each diet, 0.7 g D2O was given per kilogram of body water and deuterium
      incorporation into the erythrocyte cholesterol pool was measured for 24 hours.
      Urinary mevalonate levels were also determined in samples obtained during two
      consecutive 24-hour periods. Both techniques provided measurements of whole-body
      cholesterol biosynthesis. In all subjects the cholesterol synthesis rate as
      measured by deuterium incorporation was significantly lower (P < .05) after the
      transition from low- to medium- and low- to high-cholesterol diets. Urinary
      mevalonate excretion decreased after the change from the medium- to high- (P <
      .05) and low- to high- (P < .01) cholesterol diets. Although correspondence
      between the two methods was poor, they both indicated some suppression of
      cholesterol synthesis by dietary cholesterol. The response of cholesterogenesis
      to different amounts of dietary cholesterol was related to the rate of synthesis
      under depressed conditions of the low-cholesterol diet. These findings indicate
      modest downregulation of synthesis in response to dietary cholesterol in humans,
      independent of plasma cholesterol levels.

PMID- 8857918
TI  - ApoB-100 secretion by HepG2 cells is regulated by the rate of triglyceride
      biosynthesis but not by intracellular lipid pools.
AB  - Triglycerides (TGs), cholesteryl esters (CEs), cholesterol, and
      phosphatidylcholine have been independently proposed as playing regulatory roles
      in apoB-100 secretion; the results depended on the cellular model used. In this
      study, we reinvestigate the role of lipids in apoB-100 production in HepG2 cells
      and in particular, we clarify the respective roles of intracellular mass and the
      biosynthesis of lipids in the regulation of apoB-100 production. In a first set
      of experiments, the pool size of cholesterol, CEs, and TGs was modulated by a 3
      day treatment with either lipid precursors or inhibitors of enzymes involved in
      lipid synthesis. We used simvastatin (a hydroxymethylglutaryl coenzyme A
      reductase inhibitor), 58-035 (an acyl coenzyme A cholesterol acyltransferase
      inhibitor), 5-tetradecyloxy-2-furancarboxylic acid (TOFA, an inhibitor of fatty
      acid synthesis), and oleic acid. The secretion rate of apoB-100 was not affected
      by the large modulation of lipid mass induced by these various pre-treatments. In
      a second set of experiments, the same lipid modulators were added during a 4-hour
      labeling period. Simvastatin and 58-035 inhibited cholesterol and CE synthesis
      without affecting apoB-100 secretion. By contrast, treatment of HepG2 cells with
      TOFA resulted in the inhibition of TG synthesis and apoB-100 secretion. This
      effect was highly specific for apoB-100 and was reversed by adding oleic acid,
      which stimulated both TG synthesis and apoB-100 secretion. Moreover, a
      combination of oleic acid and 58-035 inhibited CE biosynthesis and increased both
      TG synthesis and apoB-100 secretion. These results show that in HepG2 cells TG
      biosynthesis regulates apoB-100 secretion, whereas the rate of cholesterol or CE
      biosynthesis has no effect.

PMID- 8857919
TI  - Autoantibodies against oxidized LDL do not predict atherosclerotic vascular
      disease in non-insulin-dependent diabetes mellitus.
AB  - Accelerated atherosclerosis in diabetes has been suggested as being due to an
      enhanced oxidative modification of LDL. We hypothesized that the titers of
      autoantibodies against oxidized LDL (oxLDL) may be increased in patients with non
      insulin-dependent diabetes mellitus (NIDDM) and that they may contribute to
      various manifestations of atherosclerosis among such patients. In a 10-year
      follow-up study of 91 newly diagnosed NIDDM patients and 82 nondiabetic control
      subjects, autoantibodies against oxLDL (expressed as the ratio of autoantibodies
      against oxLDL and native LDL) were measured at baseline and after 10 years.
      Quantitative ultrasonography to examine the intimal-medial thickness of the
      common carotid artery (a morphological index of arterial wall injury) and carotid
      bifurcation was performed at the 10-year examination. The relationship of
      autoantibodies against oxLDL to the occurrence of cardiovascular death, fatal and
      nonfatal myocardial infarction, stroke, and any cardiovascular event as well as
      to the intimal-medial thickness of the common carotid artery and carotid
      bifurcation was evaluated. Associations between these autoantibodies and
      metabolic variables (fasting glucose, glycosylated hemoglobin, insulin, and serum
      lipids) in NIDDM patients were also examined. Autoantibodies against oxLDL did
      not differ between NIDDM and control subjects (NIDDM: baseline, 1.63 and 0.61 to
      23.6; 10-year examination, 1.64 and 0.06 to 59.0; control group: baseline, 1.84
      and 0.13 to 36.0; 10-year examination, 1.50 and 0.25 to 8.29; median and range, P
      = .62, baseline; P = .45, 10 year). In both groups, the titers of these
      autoantibodies measured at baseline and after 10 years significantly correlated
      with each other (r = .63 for the diabetic and r = .51 for the control group,
      respectively, P < .001 for each). The frequency of all cardiovascular events was
      markedly higher in the NIDDM group than in the control group, but autoantibodies
      against oxLDL had no significant association with any of these events, including
      cardiovascular mortality. At the 10-year examination the intimal-medial thickness
      of the common carotid artery (1.24 +/- 0.36 versus 1.06 +/- 0.30 mm, P = .002)
      and carotid bifurcation (2.11 +/- 0.73 versus 1.77 +/- 0.82 mm, P = .01) were
      greater in NIDDM patients than in control subjects, but autoantibodies did not
      show any association with the intimal-medial thicknesses in either the diabetic
      or control groups. Autoantibodies against oxLDL indicate the presence of
      oxidatively modified LDL in vivo, but their titers in the serum do not seem to
      associate with the excess cardiovascular mortality, morbidity, or intimal-medial
      thickness of the carotid artery.

PMID- 8857920
TI  - Paraoxonase genotypes, lipoprotein lipase activity, and HDL.
AB  - Paraxonase, an enzyme associated with the high density lipoprotein (HDL)
      particle, hydrolyzes paraoxon, the active metabolite of the insecticide
      parathion. Several studies have shown that paraxonase levels in humans have a
      distribution characteristic of two alleles, one with low activity and the other
      with high activity. Paraoxonase also has arylesterase activity, which does not
      exhibit activity polymorphism and can therefore serve as an estimate of enzyme
      protein. Although the ability of paraoxon to irreversibly inhibit lipoprotein
      lipase (LPL) has been exploited experimentally for many years, the role of plasma
      paraoxonase in lipoprotein metabolism is unknown. Seventy-two normal individuals
      were examined for paraoxonase genotypes, plasma paraoxonase and arylesterase
      activities, postheparin LPL and hepatic lipase (HL) activities, and lipoprotein
      levels to determine whether (1) paraoxonase activity or genotype determines
      lipoprotein levels via an effect on LPL or HL activity or (2) variation in LPL
      and HL activities determines HDL levels and indirectly affects paraoxonase
      activity and protein levels in plasma. In the entire group, paraoxonase activity
      was related to arylesterase activity and genotype. Whereas arylesterase activity
      was correlated with HDL cholesterol (HDL-C) and apolipoproteinA-I (apoA-I)
      levels, neither arylesterase nor paraoxonase was correlated with LPL or HL
      activity. Furthermore, LPL activity was positively correlated and HL inversely
      correlated with HDL cholesterol and apoA-I levels, whereas LPL was inversely
      correlated with triglyceride levels. The paraoxonase genotypes of the study group
      were 30 individuals homozygous for the low-activity allele, 38 heterozygotes, and
      4 individuals homozygous for the high-activity allele. Paraoxonase genotype
      accounted for approximately .75 of the variation in paraoxonase activity.
      Paraoxonase activity was linearly related to arylesterase activity within each
      subgroup. No difference in either LPL or HL activity was seen as a function of
      paraoxonase genotype, nor were differences seen in plasma triglyceride or HDL-C
      by genotype by ANOVA. The relation between LPL and HL and components of HDL in
      the paraoxonase genotypic subgroups in general reflected the associations seen in
      the group as a whole. Multivariate analysis showed that LPL, HL, and
      arylesterase, a measure of paraoxonase mass, were independent predictors of HDL
      cholesterol, while paraoxonase genotype or activity was not. Thus, variation in
      LPL and HL appears to be significantly related to HDL cholesterol and apoA-I
      levels. The levels of HDL are a major correlate of paraoxonase protein levels,
      while paraoxonase genotype is the major predictor of plasma paraoxonase activity.

PMID- 8857921
TI  - Apolipoprotein E alleles and risk of coronary disease. A meta-analysis.
AB  - A meta-analysis was undertaken to assess the impact of apolipoprotein E (apo E)
      alleles (epsilon 2, epsilon 3, and epsilon 4) on coronary disease in 14 published
      observational studies (9 clinical coronary disease and 5 coronary angiography).
      In comparison with epsilon 3, the epsilon 4 allele was associated with greater
      odds for coronary heart disease, and summary estimates of the odds ratios (ORs)
      and (95% confidence intervals) for both sexes combined were OR = 0.98 (0.85-1.14)
      for epsilon 2 and OR = 1.26 (1.13-1.41) for epsilon 4. Separate analyses for men
      and women showed similar associations. In angiographic studies the relative odds
      for significant coronary artery disease among both sexes combined was OR = 0.76
      (0.55-1.05) for epsilon 2 and OR = 1.11 (0.88-1.40) for epsilon 4. The overall
      impression is that epsilon 4 is associated with clinical and coronary disease and
      that results are similar in men and women.

PMID- 8857922
TI  - Role of NO in flow-induced remodeling of the rabbit common carotid artery.
AB  - Flow-induced changes in vessel caliber tend to restore baseline wall shear stress
      (WSS) and have been reported to be endothelium-dependent. To investigate the role
      of endothelium-derived nitric oxide (NO) in the adaptive increase in artery
      diameter in response to a chronic increase in blood flow, an arteriovenous
      fistula was constructed between the left common carotid artery (CCA) and the
      external jugular vein in 22 New Zealand White rabbits, and NO synthesis was
      inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl
      ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals
      served as controls. Mean arterial blood pressure was not significantly altered by
      L-NAME treatment (91 +/- 2 in control versus 98 +/- 3 mm Hg in L-NAME-treated
      rabbits). Blood flow significantly increased in the left CCA in both groups but
      was lower in L-NAME-treated than control animals (106.1 +/- 10.7 versus 196.2 +/-
      32.3 mL/min, P < .003). The diameter of the flow-loaded left CCA also increased
      significantly in both groups compared with the right CCA (2.15 +/- 0.12 and 2.54
      +/- 0.1 mm, respectively, P < .02), but the increase was less in the L-NAME
      treated than the control group (3.24 +/- 0.09 and 4.64 +/- 0.17 mm, respectively,
      P < .0001). The diameter of the anastomosed veins was also increased but to a
      much lesser degree in L-NAME-treated animals than in controls (4.14 +/- 0.29
      versus 7.94 +/- 0.51 mm, P < .0001). As a result of artery enlargement, WSS was
      normalized in the flow-loaded left CCA of the control group (8.87 +/- 0.77
      dynes/cm2) regardless of blood flow values. In L-NAME-treated animals, however,
      WSS was only partially regulated, the mean value being significantly increased
      (18.7 +/- 2.2 dynes/cm2, P < .006). Moreover, a highly significant positive
      correlation between WSS and blood flow was obtained in L-NAME-treated animals (r
      = .84, P < .0001). We also found remodeling of the artery wall, with a larger
      increase in the medial cross-sectional area associated with an increased number
      of smooth muscle cells, in the control group compared with the L-NAME-treated
      group (0.75 +/- 0.09 versus 0.49 +/- 0.04 mm2 and 4504 +/- 722 versus 2717 +/-
      282 cells/mm2, P < .03). We conclude that NO plays a role in the increase of
      vessel caliber in response to chronic increase in blood flow. As yet unidentified
      additional metabolic processes appear to be necessary for a complete regulatory
      response.

PMID- 8857923
TI  - Endothelial cells inhibit NO generation by vascular smooth muscle cells. Role of
      transforming growth factor-beta.
AB  - Endothelial cell (EC)-released agents are active regulators of vascular smooth
      muscle cell (VSMC) functions. The first aim of the present work was to analyze
      the effect of ECs on interleukin-1 beta (IL-1 beta)-induced NO production by
      SMCs. Bovine aortic ECs (BAECs) and BVSMCs in culture were used for the study. IL
      1 beta (0.03 U/L) stimulated nitrite production by BVSMCs. This increase was
      smaller in the presence of BAECs. This effect was accompanied by reduced
      expression of inducible NO synthase (iNOS) in BVSMCs coincubated with BAECs, as
      analyzed by Western blot analysis. The reduction in iNOS protein expression was
      partially reversed by a polyclonal antibody against transforming growth factor
      beta (TGF-beta). Furthermore, we examined the cytotoxic effect of the NO released
      from BVSMCs on both BAECs and the BVSMCs themselves. Incubation of BAECs with IL
      1 beta-prestimulated BVSMCs induced EC toxicity, which was partially inhibited by
      an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester, or an inhibitor
      of iNOS expression, dexamethasone. No cytotoxic effect of IL-1 beta on BVSMCs
      themselves was detected. ECs modulate iNOS expression in SMCs by mechanisms that
      include a TGF-beta-dependent pathway. The NO released from SMCs exerts cytotoxic
      effects on the adjacent endothelium without altering the viability of the SMCs.

PMID- 8857924
TI  - Contrasting effects of plasminogen activators, urokinase receptor, and LDL
      receptor-related protein on smooth muscle cell migration and invasion.
AB  - Smooth muscle cell (SMC) migration is an early response to vascular injury and
      contributes to the development of intimal thickening. Upregulation of several
      components of the plasminogen activator (PA) system has been documented after
      vascular injury. Utilizing a Transwell filter assay system and human umbilical
      vein SMCs, we sought to define the role of four different PA system components on
      SMC migration and matrix invasion: (1) PAs, (2) plasmin, (3) PA receptors, and
      (4) PA clearance receptors (ie, low density lipoprotein receptor-related protein
      [LRP]). Addition of active two-chain urokinase-type PA (UPA) stimulated random
      migration (192 +/- 30% of control, 0.36 nmol/L, P < .001). The stimulation was
      inhibited by pretreatment with diisopropylfluorophosphate, PA inhibitor type 1
      (PAI-1), or aprotinin, a plasmin inhibitor. Augmented migration was also observed
      with either low-molecular-weight UPA or the amino terminal fragment of UPA (ATF),
      with the effects being additive. Stimulation by ATF alone, however, was not
      inhibited by aprotinin. The stimulatory effect was not specific for UPA, in that
      tissue-type PA (TPA) also increased migration (169 +/- 9% of control, 10 nmol/L,
      P < .001); the augmentation was inhibited by pretreatment with DFP, PAI-1, or
      aprotinin and was additive to the UPA effect. Antibodies to the UPA receptor but
      not 5'-nucleotidase (another glycosylphosphatidylinositol-anchored cell surface
      protein) inhibited baseline and UPA-stimulated migration. Similarly, both UPA and
      TPA stimulated invasion of a collagen gel; this augmentation was inhibited by
      aprotinin, whereas antibodies to the UPA receptor reduced baseline invasion.
      Finally, we tested whether inhibition of LRP function, which mediates
      internalization of PA/inhibitor complexes, affected either process. Both
      antibodies to LRP and recombinant receptor associated protein, a known inhibitor
      of ligand binding to the LRP, significantly inhibited migration but did not
      affect collagen gel invasion. These data demonstrate the ability of several
      components of the PA system to modulate SMC migration and invasion in vitro via
      plasmin-dependent and -independent mechanisms.

PMID- 8857925
TI  - High concentrations of active plasminogen activator inhibitor-1 in porcine
      coronary artery thrombi.
AB  - Addition of exogenous plasminogen activator inhibitor-1 (PAI-1) to fibrin clots
      inhibits fibrinolysis in vivo. However, it is unknown whether the localized
      concentrations of active PAI-1 necessary to produce this antifibrinolytic effect
      can be recruited to acute arterial thrombi by endogenous mechanisms. We measured
      PAI-1 activity and antigen in porcine coronary artery thrombi that formed in
      response to acute vascular injury. Mean PAI-1 activity in thrombi (n = 5) was 36
      +/- 5.1 micrograms/mL, which is > 2000 times its concentration in normal porcine
      plasma. The presence of markedly elevated concentrations of active PAI-1 in
      thrombi was confirmed by an immunoactivity assay and by demonstrating formation
      of sodium dodecyl sulfate-stable complexes after addition of 125I-urokinase to
      thrombus extracts. Comparative analysis of PAI-1 antigen by Western blotting and
      urokinase inhibition assay suggested that approximately one third of thrombus
      associated PAI-1 was active. Histological examination of coronary thrombi
      revealed that they consisted predominantly of dense aggregates of platelets with
      interspersed islands of fibrin, which closely resemble the histological
      appearance of thrombi in patients with myocardial infarction and unstable angina
      pectoris. Washed porcine platelets prepared from peripheral blood contained
      sufficient PAI-1 antigen and activity to account for the concentrations observed
      in coronary artery thrombi. However, the specific activity of human platelet PAI
      1 was lower than that of porcine platelet PAI-1 (2% versus 50% active,
      respectively), and human platelets inhibited in vitro fibrinolysis to a lesser
      extent than did porcine platelets. These results indicate that active PAI-1
      accumulates in porcine coronary artery thrombi in concentrations markedly higher
      than those present in plasma and that PAI-1 may be an important determinant of
      the known resistance of platelet-rich thrombi to lysis by tissue-type plasminogen
      activator. These studies also underscore the importance of considering possible
      species differences in protein function when comparing animal models of
      thrombosis to acute coronary thrombosis in humans.

PMID- 8857926
TI  - Sustained inhibition of whole-blood clot procoagulant activity by inhibition of
      thrombus-associated factor Xa.
AB  - Progression of arterial thrombosis partly depends on thrombus-associated thrombin
      and activated factor X (Xa) activity. However, whether Xa or thrombin is the most
      appropriate target for inhibition of recurrent thrombosis is unknown. This study
      was designed to determine whether inhibition of Xa results in more sustained
      attenuation of thrombus-associated precoagulant activity than does inhibition of
      thrombin. Clots prepared ex vivo from human whole blood and pathological arterial
      thrombi from patients were preincubated in citrated plasma containing no
      inhibitor, 0.5 to 1 U/mL heparin, 0.5 to 1 mumol/L hirudin, 5 to 10 mumol/L tick
      anticoagulant peptide (TAP), 0.15 to 3 mumol/L tissue factor pathway inhibitor
      (TFPI), or a combination of 1 mumol/L hirudin and 10 mumol/L TAP for 2 hours.
      After preincubation the clots were removed from first-stage plasma, extensively
      washed in phosphate-buffered saline, and added to nonanticoagulated whole blood.
      Clots preincubated in plasma without inhibitors induced marked activation of the
      coagulation system in whole blood, as characterized by greater increases in the
      concentration of fibrinopeptide A (FPA) over 7 minutes than in blood without
      added clots (1522 +/- 568 compared with 117 +/- 170 ng/mL, P < .01).
      Preincubation of clots with heparin or hirudin did not attenuate the increases in
      FPA in wholeblood. In contrast, compared with incubation without an inhibitor,
      preincubation of clots with TAP or TFPI markedly attenuated the increases in FPA
      when clots were added to whole blood (551 +/- 316 and 508 +/- 208 ng/mL,
      respectively, P < .01). Similar results were obtained with arterial thrombi from
      patients. Inhibition of Xa but not of thrombin results in sustained attenuation
      of thrombus-associated procoagulant activity. Uninhibited thrombus-associated Xa
      activity may account for the increases in thrombin activity that are commonly
      observed in clinical trials after discontinuation of thrombin inhibitors.

PMID- 8857927
TI  - Thrombin inhibition by antithrombin III on the subendothelium is explained by the
      isoform AT beta.
AB  - Balloon injury of the rabbit aorta results in thrombin coagulant activity on the
      injured vessel wall that causes fibrin formation. The anticoagulant activity of
      both the intact and injured vessel wall has been partly explained by
      glycosaminoglycans with heparin-like activity that augment that activity of
      antithrombin III (AT). AT exists in two isoforms, alpha and beta, AT beta, which
      constitutes only 5% to 10% of AT in plasma, lacks one carbohydrate side chain,
      has higher affinity for glycosaminoglycans, and associates more readily with the
      subendothelium. This study evaluated whether AT can inhibit thrombin on the
      injured vessel wall and, if so, whether one of the isoforms is more effective
      then the other. The two isoforms were isolated from human plasma by heparin
      Sepharose chromatography, and the purity was investigated by isoelectric focusing
      and crossed immunoelectrophoresis. Rabbits were subjected to balloon injury of
      the aorta; 3 hours after injury the aorta was excised. Thrombin coagulant
      activity on the aorta was measured by exposure to fibrinogen and thereafter by
      measuring the generation of fibrinopeptide A. Injured animals were treated with
      AT, AT alpha, or AT beta and were compared with control animals. AT was
      demonstrated on the injured vessel wall by using an immunohistochemical method.
      Animals receiving crude AT had significantly lower amounts of thrombin coagulant
      activity on the injured aortic wall than control animals, but AT alpha at a
      comparable dose had no effect. AT beta was given in the same dose as crude AT and
      also at a dose (10%) proportional to its presence in plasma. Animals receiving AT
      beta had significantly lower values of thrombin on the injured aortic wall than
      control animals. We conclude that the inhibitory effect of AT on thrombin
      coagulant activity on the injured vessel wall in explained by its AT beta
      content.

PMID- 8857928
TI  - Transforming growth factor-beta 1 expression and myofibroblast formation during
      arterial repair.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) plays a central role in tissue
      repair owing to its modulating effects on cell growth and the synthesis of
      extracellular matrix. We have previously shown that adventitial fibroblasts
      differentiate to myofibroblasts after endoluminal injury, thereby contributing to
      arterial remodeling. Since TGF-beta 1 exerts several biologic actions attributed
      to myofibroblasts, we examined its role in myofibroblast formation in a porcine
      model of balloon overstretch coronary artery injury. TGF-beta 1 transcripts were
      induced in numerous adventitial cells 2 days after injury (47 +/- 10%, P < .001
      versus control). These cells displayed no smooth muscle (SM) markers, i.e., alpha
      SM actin or desmin, which suggested their fibroblastic origin. This was further
      corroborated by the rare presence of macrophages in the injured adventitia (3 +/-
      1%). At 7 to 8 days, most TGF-beta 1-expressing cells demonstrated alpha-SM actin
      immunoreactivity. Their myofibroblast phenotype was confirmed by electron
      microscopy, which revealed microfilaments (stress fibers) and a well-developed
      rough endoplasmic reticulum. The distribution of TGF-beta 1 transcripts by in
      situ hybridization was paralleled by the immunolocalization of intracellular and
      extracellular TGF-beta 1 epitopes. At later times (> 14 days after injury), the
      decrease in TGF-beta 1 coincided with the disappearance of adventitial
      myofibroblasts, whereas the neointima exhibited longer TGF-beta 1 expression. In
      conclusion temporal and spatial relationships between TGF-beta 1 and
      myofibroblast formation suggest an important role for autocrine TGF-beta 1 in the
      phenotypic modulation of vascular fibroblasts. Induction of TGF-beta 1 expression
      may provide a differentiation signal for adventitial fibroblasts to become
      myofibroblasts, which affect arterial remodeling via their mechanical and
      synthetic properties.

PMID- 8857929
TI  - Comparison of the effects of the thrombin inhibitor r-hirudin in four animal
      models of neointima formation after arterial injury.
AB  - Thrombin has been implicated as a contributing factor to restenosis after vessel
      reopening procedures. We compared the ability of the direct thrombin inhibitor
      recombinant (r-) hirudin to reduce neointimal growth in different animal models
      of arterial injury. Carotid arteries of rats, rabbits, and hypercholesterolemic
      minipigs were injured by withdrawal of an inflated balloon catheter. In addition,
      we used a double-lesion model in rabbits, which involved balloon angioplasty of a
      preexisting lesion induced by carotid denudation 4 weeks earlier. r-Hirudin was
      given in all four animal models as a short-term application (bolus of 1 mg/kg
      i.v. immediately before injury, followed by infusion of 1 mg.kg-1.h-1 for 2
      hours, and an injection of 6 mg/kg SC). Additionally, we investigated the effects
      of prolonged treatment (intravenous infusion for 3 and 14 days) in rats.
      Inhibition of thrombin was monitored by determination of activated partial
      thromboplastin time, and histomorphometric analysis of the arteries was performed
      after 2 (rats) or 4 (rabbits and minipigs) weeks. In rabbits, short-term r
      hirudin treatment reduced neointimal area by 59% (single-injury model, P = .05)
      and 44% (double-injury model, P = .02). In rats and minipigs no inhibition of
      neointimal growth was observed after short-term r-hirudin application. A 3- or 14
      day infusion of r-hirudin in rats, however, resulted in 25% (P = .007) and 27% (P
      = .003) reductions in neointimal area, respectively. In conclusion, there is
      considerable interspecies variation in the time frame of susceptibility for
      reduction of neointimal growth by inhibition of thrombin after arterial injury.
      These results demonstrate the importance of testing potential antirestenotic
      treatments in an array of different animal models.

PMID- 8857930
TI  - Monocyte recruitment and neointimal hyperplasia in rabbits. Coupled inhibitory
      effects of heparin.
AB  - Among the many effects of heparin independent of its effects on coagulation are
      inhibition of vascular smooth muscle cell proliferation and regulation of
      leukocyte-blood vessel interactions. The potential link between these effects was
      examined in an animal model of vascular injury rich in inflammatory cells: the
      placement of endovascular metal stents in rabbit iliac arteries. Monocyte
      adhesion stimulated by early focal thrombus was maximal after 3 days, with
      infiltrating monocytes and intimal cell proliferation maximal after 7 days.
      Tissue monocyte number dictated cell proliferation at each time point (R2 = .92,
      P < .0001). Heparin reduced both early monocyte adhesion as well as monocyte
      infiltration within the neointima 7 and 14 days after stent placement. Reductions
      in adherent and tissue monocytes were commensurate with reductions in intimal
      cell proliferation and intimal thickening. At 14 days, heparin's inhibition of
      mononuclear cell adhesion was correlated with its suppression of intimal
      thickening (R2 = .82, P < .0001). Monocytes have been hypothesized to serve as
      markers, initiators, and promoters of arterial occlusive diseases. Heparin's
      ability to inhibit mononuclear cell adhesion and penetration and reduce
      neointimal size and cell proliferation after vascular injury may further
      implicate monocytes in the pathogenesis of neointimal hyperplasia after
      mechanical arterial injury.

PMID- 8857931
TI  - Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome.
AB  - Hypereosinophilic syndromes may result either from eosinophilic differentiation
      of a clone of neoplastic cells or from reactive eosinophilia. In other patients
      HES is idiopathic. It appears likely that in many patients the "idiopathic'
      hypereosinophilic syndrome is actually a chronic myeloproliferative disorder.
      Those cases showing an increase of blast cells or a demonstrable clonal
      cytogenetic abnormality should be classified as eosinophilic leukaemia. In other
      cases the neoplastic nature of the disease can be recognized only in retrospect
      when a granulocytic sarcoma or AMI, develops. A few cases of idiopathic HES are
      consequent on cytokine secretion whereas others remain idiopathic at the time of
      death. When eosinophilia occurs as a feature of an acute or chronic myeloid
      leukaemia or a chronic myeloproliferative disorder the eosinophils are usually
      part of the leukaemic clone. However, eosinophilia in association with acute
      lymphoblastic leukaemia is usually reactive. Rare cases have a biphenotypic
      leukaemia/lymphoma with both eosinophils and lymphoid cells arising from a mutant
      pluripotent stem cell.

PMID- 8857932
TI  - Cellular and molecular mechanisms in chronic myeloid leukaemia: biology and
      treatment.

PMID- 8857933
TI  - Guidelines on the investigation and management of thrombocytopenia in pregnancy
      and neonatal alloimmune thrombocytopenia. Maternal and Neonatal Haemostasis
      Working Party of the Haemostasis and Thrombosis Task Force of the British Society
      for Haematology.

PMID- 8857934
TI  - Erythropoietin production by interstitial cells of hypoxic monkey kidneys.
AB  - Previous studies which demonstrated that interstitial cells of the peritubular
      capillary bed of the kidneys are the site of erythropoietin (Epo) production have
      been performed in non-primate species. In this study, kidneys from adult rhesus
      monkeys exposed to 18 h hypoxia (0.42 atm) with high serum (5685 mU/ml) and
      kidney (814 mU/g. includes serum EPO in the kidney) levels of Epo were compared
      with a kidney from a nonhypoxic normal rhesus monkey. Localization of Epo mRNA by
      in situ hybridization was carried out with either anti-sense or sense RNA probes
      generated from a 645 base pair KpnI-BgIII fragment of a monkey Epo cDNA. Epo mRNA
      was demonstrated only in interstitial cells in the peritubular capillary bed of
      the hypoxic and normal monkey kidneys utilizing the antisense probe. The finding
      that the same type of cell that produces EPO in mice, rats and sheep also
      produces EPO in a higher primate species strongly supports the contention that
      renal interstitial cells also produce EPO in the human.

PMID- 8857935
TI  - Effects of immunosuppressive drugs and antibiotics on GM-CSF and G-CSF secretion
      in vitro by monocytes, T lymphocytes and endothelial cells.
AB  - We studied the effects of eight antibiotics, cyclosporin and corticosteroids on
      the in vitro secretion of GM-CSF and G-CSF by monocytes. T lymphocytes and
      endothelial cells. The aim was to evaluate a possible mechanism for these drugs
      in the delay of haemopoietic recovery after high-dose chemotherapy or bone marrow
      transplantation. Corticosteroids were prominent inhibitors of GM-CSF secretion by
      monocytes and T lymphocytes, but not by endothelial cells. In contrast, G-CSF
      secretion by monocytes was unchanged whereas that of endothelial cells was
      enhanced in the presence of corticosteroids. Cyclosporin efficiently down
      regulated GM-CSF secretion by T lymphocytes and had also a minor effect on CSF
      secretion by endothelial cells, whereas monocyte secretion was unaffected.
      Stimulated T lymphocytes derived from patients under treatment with cyclosporin
      had impaired capacity to secrete GM-CSF compared to controls. Among the
      antibiotics, cephalosporins inhibited GM-CSF secretion by T lymphocytes, and GM-
      and G-CSF secretion by endothelial cells. Ciprofloxacin and sulphmethoxazole had
      minor effects on GM-CSF secretion by T lymphocytes and endothelial cells. No
      antibiotic significantly influenced GM-CSF secretion by monocytes.

PMID- 8857936
TI  - Progenitor cell yield in sequential blood stem cell mobilization in the same
      patients: insights into chemotherapy dose escalation and combination of
      haemopoietic growth factor and chemotherapy.
AB  - Between April 1988 and March 1994 a total of 23 patients with haematological or
      non-haematological malignancies received serial peripheral blood stem cell (PBSC)
      mobilization to attain sufficient harvest for PBSC transplant at our institution.
      There was no improvement in yield with the second mobilization for group A
      patients (n = 12) who had the same dose of cyclophosphamide twice as mobilizing
      agent. For group B patients (n = 6). who had a higher dose of cyclophosphamide
      with the second mobilization, there was significant increase in CFU-GM yield.
      CD34+ cell yield was not measured. For group C patients, who received interleukin
      3 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with the first
      mobilization and chemotherapy plus GM-CSF with the second, there was significant
      increase in CFU-GM as well as CD34+ cell yield. Our results demonstrate that, at
      the doses studied, chemotherapy dose escalation and combining haemopoietic growth
      factor with chemotherapy improve progenitor cell yield in PBSC mobilization.

PMID- 8857937
TI  - Impaired migration in vitro of neutrophils from patients with paroxysmal
      nocturnal haemoglobinuria.
AB  - Migration of neutrophils in patients with paroxysmal nocturnal haemoglobinuria
      (PNH) was studied using two different complement-free in vitro model systems,
      subagarose and transendothelial migration. In the subagarose migration assay the
      mean migration distance of PNH neutrophils was slightly, but significantly,
      reduced to 1236 microns (range 753-1586, n = 6) compared to a normal mean of 1476
      microns (range 1076-1768, n = 6, P = 0.016). By immunocytochemical staining for
      the urokinase type plasminogen activator receptor (uPAR) which is a glycosyl
      phosphatidyl-inositol (GPI) anchored protein expressed by normal, but not by PNH
      affected, neutrophils, it was shown that the uPAR-positive subpopulation of
      normal neutrophils predominated among the faster migrating cells (60-80% normal
      cells at the front of migration) while uPAR-negative (i.e. PNH-affected
      neutrophils) were more numerous close to the application well (5-30% normal
      cells). When migration of neutrophils was tested across a monolayer of human
      umbilical vein endothelial cells (HUVEC) cultured on polycarbonate filters, there
      was a 3-4-fold impairment of the migration of the PNH-affected neutrophils both
      in the absence of stimulation and after stimulation with fMLP (P < 0.001 in both
      cases). After IL-1 stimulation of the endothelium the impairment was even more
      pronounced (8-fold difference, P < 0.001). When the endothelial cells were grown
      on collagen-coated filters the impairment of the migration of PNH neutrophils was
      less pronounced, but still significant after stimulation with fMLP and IL-1 (2
      fold, P < 0.05 in both cases). These results demonstrate that there is a
      complement-independent impairment of migration of neutrophils from patients with
      PNH which may be related to their failure to express GPI-linked proteins involved
      in cell migration and/or adhesion such as the uPA receptor and the CD66b antigen.

PMID- 8857938
TI  - Thymoma and agranulocytosis: two case reports and literature review.
AB  - Thymoma with agranulocytosis is a rare association. We describe two cases of
      agranulocytosis presenting with sepsis which were both found to have coincident
      benign spindle cell thymomas. One case, associated with promyelocyte arrest and
      hypogammaglobulinaemia, was treated successfully with granulocyte colony
      stimulating factor (G-CSF). Thymectomy had no effect. The other case, associated
      with complete myeloid aplasia, proceeded to a fatal outcome after failure of
      treatment with granulocyte-macrophage colony stimulating factor (GM-CSF),
      plasmapheresis, thymectomy, intravenous immunoglobulin, cyclophosphamide and
      methylprednisolone. We also review the literature of thymoma in association with
      agranulocytosis.

PMID- 8857939
TI  - Epidemiological studies of spectrin mutations related to hereditary
      elliptocytosis and spectrin polymorphisms in Benin.
AB  - We studied an African population in Benin and discovered an unexpectedly high
      frequency (1.6%) of hereditary elliptocytosis (HE) among the 1447 subjects
      studied. In approximately two-thirds of HE individuals we identified molecular
      defects, primarily those in erythrocyte alpha-spectrin (dupL154, L260P and L207P
      mutations), as well as a novel mutation of erythrocyte beta-spectrin (beta-W2061R
      mutation). We also identified the genetic basis of a previously identified
      protein polymorphism of the alpha III domain of spectrin (R1331I mutation). The
      genetic background of HE in the African population was studied using a number of
      polymorphisms of the alpha-spectrin gene, including the alpha III domain
      polymorphism. These studies suggest that the HE mutations appear to have
      originated from separate genetic backgrounds in this population.

PMID- 8857940
TI  - A new type of hereditary persistence of fetal haemoglobin (HPFH): HPFH Tunisia
      beta + (+C-200)G gamma.
AB  - Nd-HPFH are haematological conditions which are natural models to aid
      understanding of the haemoglobin (Hb) switch. In this paper we describe a new non
      deletional hereditary persistence of fetal haemoglobin (nd-HPFH) associated with
      the highest Hb F level observed to date (up to 49% without haemopoietic stress).
      Sequence of the G gamma promoter revealed a cytidine insertion within a stretch
      of four cytidines, located between -200 and -203 bp with respect to the cap site.
      This insertion is situated within a polypyrimidine-polypurine region which can
      adopt a triple helix structure, and is therefore of particular interest with
      respect to the Hb switch mechanism.

PMID- 8857941
TI  - Congenital dyserythropoiesis characterized by marked macrocytosis, vitamin B12-
      and folate-independent megaloblastic change and absence of the defining features
      of congenital dyserythropoietic anaemia types I or III.
AB  - Four patients with congenital dyserythropoiesis characterized by marked
      macrocytosis, little or no anaemia, and vitamin B12- and folate-independent
      megaloblastic erythropoiesis are reported. Their erythroblasts also showed
      various dysplastic changes but not those diagnostic for congenital
      dyserythropoietic anaemia (CDA) types I or III. The haematological features of
      the four patients, who included two siblings, resemble those of a previously
      reported patient and together these patients form a recognizable subgroup within
      those cases of CDA not belonging to CDA types I-III. In two of the cases studied,
      and possibly a third, the inheritance was as an autosomal recessive character.

PMID- 8857942
TI  - The effect of the chemokine rhMIP-1 alpha, and a non-aggregating variant BB
      10010, on blast cells from patients with acute myeloid leukaemia.
AB  - The effects of recombinant macrophage inflammatory protein 1 alpha (rhMIP-1
      alpha) on the proliferation of leukaemic blast cells from patients with acute
      myeloid leukaemia was assessed. Using the previously described [3H]thymidine
      incorporation index assay, the response of autonomous and growth factor
      responsive AML blast cells to the chemokine rhMIP-1 alpha was measured. In the
      case of autonomous proliferators, rhMIP-1 alpha had no inhibitory effect on
      [3H]thymidine incorporation and in 4/6 cases [3H]-thymidine incorporation was
      stimulated by rhMIP-1 alpha. In the presence of stem cell factor (SCF), a
      majority (8/9) of the samples which responded to this growth factor were
      inhibited when rhMIP-1 alpha was included in the assay medium. Similar results
      were obtained with GM-CSF-responsive samples; however, when these two cytokines
      were combined, only 3/14 were significantly inhibited. In the presence of human
      placental conditioned medium (HPCM), rhMIP-1 alpha significantly inhibited
      [3H]thymidine incorporation in only 2/10 of HPCM-responsive samples. In
      methylcellulose assays rhMIP-1 alpha had no consistent effect on colony/cluster
      formation in the presence of either GM-CSF + SCF or HPCM. Similar results were
      obtained with BB-10010, a mutant of rhMIP-1 alpha which has defined aggregation
      properties in solution. These data suggest that autonomously proliferating AML
      cells, and also some AML samples which require cytokines to proliferate, are non
      responsive to the growth inhibitors rhMIP-1 alpha and BB-10010 in the presence of
      multiple growth factors.

PMID- 8857943
TI  - Serial quantification of minimal residual disease of t(8;21) acute myelogenous
      leukaemia with RT-competitive PCR assay.
AB  - The chromosomal translocation (8;21)(q22;q22) in the AML M2 subtype according to
      the FAB classification, results in the production of a novel fusion gene
      AML1/ETO. The chimaeric AML1/ETO transcript is useful for the detection of
      minimal residual disease (MRD). Recently, several studies on the detection of
      AML1/ETO transcripts in t(8;21) AML have been reported. However, the clinical
      significance of a small number of AML1/ETO transcripts by a reverse transcription
      polymerase chain reaction (RT-PCR) remains to be elucidated. We have developed a
      novel quantitative RT-competitive PCR assay and evaluated the clinical usefulness
      of this method by the monitoring of MRD in eight patients with t(8;21) AML. In
      four patients in first continuous complete remission (CR) the value of MRD was
      always < 0.1 fg of the competitor dose throughout their courses, whereas in four
      relapsed patients there was an increase in the value of MRD to > 0.1 fg of the
      competitor dose before cytogenetic relapse. We conclude that the detection of the
      presence of cells with AML1/ETO fusion transcripts by our RT-competitive PCR
      assay may be useful to monitor disease progression and to predict subsequent
      relapse.

PMID- 8857944
TI  - Quantification of PML-RAR alpha transcripts in acute promyelocytic leukaemia:
      explanation for the lack of sensitivity of RT-PCR for the detection of minimal
      residual disease and induction of the leukaemia-specific mRNA by alpha
      interferon.
AB  - The RT-PCR technique for the identification of the PML-RAR alpha fusion mRNA is
      widely used for the detection of minimal residual in acute promyelocytic
      leukaemia (APL). A positive result after remission induction is highly predictive
      of early relapse, but the vast majority of patients have no detectable disease by
      this technique after chemotherapy consolidation, despite the fact that many later
      relapse. We report a quantitative PCR technique for the PML-RAR alpha cDNA which
      was used to show that less than 1000 PML-RAR alpha molecules are obtained from 1
      microgram of diagnostic bone marrow RNA derived from approximately 1 million APL
      blasts. The lack of sensitivity of currently employed RT-PCR methods may
      therefore be explained by their poor yield of PML-RAR alpha cDNA. Minor
      modifications to the reverse transcription procedure improved this yield 3 fold.
      Furthermore, expression of the leukaemia-specific transcript increased by
      approximately one order of magnitude after incubation of the patient's cells for
      24 h in vitro with 100 iu/ml alpha interferon.

PMID- 8857945
TI  - Expression of the nerve growth factor receptor c-TRK in human myeloid leukaemia
      cells.
AB  - Nerve growth factor (NGF) is of major importance for the survival, development
      and maintenance of peripheral sympathetic and central neuronal tissue. Most of
      the cellular effects are mediated by binding to their high-affinity receptor c
      TRK, a transmembrane receptor tyrosine kinase. C-TRK protein has been detected in
      neuronal tissue and also in mast cells, monocytes and some haemopoletic
      progenitor cells. Here we report c-TRK gene expression in myeloid leukaemic cell
      lines (HEL, K562 and KG-1) and for the first time in the primary leukaemic cells
      of 44% (n = 59) of patients with acute myelogenous leukaemia (AML). Moreover, in
      the human promyelocytic cell line HL-60, c-TRK expression was inducible by
      differentiation induction with tetradecanoyl-phorbol 13-acetate (TPA). In c-TRK
      gene-expressing cells the transmembrane receptor tyrosine kinase was detectable
      by Western blotting and by in vitro kinase assay. In the AML group, c-TRK
      expression was not correlated to the FAB-classified morphology or any other
      clinical parameter. In all cases tested we could not detect NGF mRNA by means of
      reverse transcriptase PCR, excluding an autocrine loop involving the TRK/NGF
      receptor-ligand system in leukaemogenesis. Our results show another example of
      possible communication between neuronal and haemopoietic tissue. However, we
      still lack positive evidence of a c-TRK function in haemopoiesis.

PMID- 8857947
TI  - Chronic persistent Epstein-Barr virus infection of natural killer cells and B
      cells associated with granular lymphocytes expansion.
AB  - B lymphocytes and epithelial cells are the only cell types known to be infected
      with Epstein-Barr virus (EBV) in normal individuals. Rarely, EBV also infects
      other cells, including natural killer (NK) cells, almost always in the context of
      fatal leukaemias or lymphoproliferative disorders. We report on a 6-year-old
      previously healthy girl who developed fevers and liver function abnormalities for
      3 months. The peripheral blood revealed an abnormal expansion of large granular
      lymphocytes, comprising 24% of the white blood cells. Flow cytometric analysis of
      the peripheral blood mononuclear cells showed an abnormal increase of CD16
      positive NK cells, 62% of which were EBV-infected by in situ EBER-1
      hybridization. The circulating B cells were normal in number, but 18% were
      infected with EBV by in situ EBER-1 hybridization. Approximately 2 years after
      resolution of all symptoms and continued good health. 35% of the circulating
      mononuclear cells were EBV-infected, indicative of persistent expansion of EBV
      infected cells. We conclude that abnormal expansions of EBV-infected NK and B
      cells can be associated with a chronic benign course.

PMID- 8857946
TI  - High response rates with short infusional 2-chlorodeoxyadenosine in de novo and
      relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.
AB  - Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non
      Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell,
      follicular mixed cell, and lymphoplasmacytoid) were treated with 2
      chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion)
      for an average of three cycles. Minor treatment delays, generally due to
      haematological toxicities, occurred in nine of 105 cycles. Major toxicities were
      lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred
      in seven patients. Overall response rate was 69% (five complete, 19 partial)
      reaching 88% for de novo patients (two complete, five partial). Elevated beta 2
      microglobulin level was negatively predictive of response (P = 0.0014). Eight of
      24 responders relapsed, with a median follow-up of 13 months. 2CdA administered
      as an intermittent infusion shows considerable single-agent activity in low-grade
      lymphomas achieving high response rates of prolonged duration. Consideration of
      schedules where 2CdA is alternatively administered with combination chemotherapy
      appears warranted.

PMID- 8857948
TI  - Changes in coagulation and fibrinolysis in childhood ALL: a two-step dose
      reduction of one E. coli asparaginase preparation.
AB  - The influence of two different E. coli asparaginase (ASP) preparations on
      fibrinolytic proteins in childhood ALL was recently reported, demonstrating a
      clearly significant association between ASP activity and haemostatic changes.
      Since the Bayer preparation is no longer available for treatment of large series
      of patients with ALL, the present study was designed to prospectively evaluate
      coagulation and fibrinolytic changes in leukaemic children receiving different
      doses of Medac ASP, which is now available for treatment of childhood ALL.
      Leukaemic children in whom ASP Medac was administered at 3 d intervals in a two
      step dose reduction (5000 IU/m2, n = 10; 2500 IU/m2, n = 15) were compared with
      children who had received Bayer ASP 10,000 IU/m2 in the same time schedule in a
      former randomized trial; at the same venipuncture, blood samples for coagulation
      studies were obtained before each ASP administration together with serum samples
      for pharmacokinetic monitoring. Compared with Bayer ASP 10,000 IU/m2, patients
      receiving Medac ASP 5000 IU/m2 showed significantly decreased values of
      fibrinogen, plasminogen, and alpha 2-antiplasmin, along with significantly
      enhanced thrombin generation. Improvement occurred in children treated with 2500
      IU/m2 Medac ASP; alpha 2-antiplasmin and D-dimer no longer differed from the
      Bayer group. Since both patient groups showed complete asparagine depletion
      during the course of ASP administration, the lower dosage of 2500 IU/m2
      administered at 3 d intervals should guarantee the specific metabolic therapy for
      ALL, leading to depletion of the circulating pool of asparagine.

PMID- 8857949
TI  - In vivo mobilization of karyotypically normal peripheral blood progenitor cells
      in high-risk MDS, secondary or therapy-related acute myelogenous leukaemia.
AB  - We have previously reported that mobilization of Philadelphia (Ph) chromosome
      negative progenitors is possible in a significant number of Ph1-positive acute
      lymphoblastic leukaemia (ALL) and chronic myelogenous leukaemia (CML) patients.
      In this pilot study we employed the same approach for patients with RAEB-t,
      secondary AML (sAML) and therapy-related AML (t-AML). All patients except one had
      double or complex cytogenetic abnormalities in marrow cells before mobilization
      therapy. All patients received an idarubicin-containing regimen (mini-ICE
      protocol) followed by rh-G-CSF and the first leukapheresis was performed as they
      were recovering from aplasia. In six out of nine patients the leukapheresis
      product was entirely karyotypically normal, combined with a significant number of
      CFU-GM. CD34+ cells and LTC-IC. Recovery time from mobilization therapy was short
      and no patient died as a result of the procedure. To date, three patients have
      undergone autografting using their karyotypically normal collections, of which
      two (sAML) are alive with karyotypically normal marrow a few months after
      autografting.

PMID- 8857950
TI  - Translocation t(3;17)(q23;q21): a new translocation in acute lymphoblastic
      leukaemia.
AB  - We report on two adult patients with CD10+ positive acute lymphoblastic leukaemia
      (ALL) who presented with similar clinical and laboratory features and with a new
      chromosomal translocation: t(3;17)(q23;q21). This translocation may be involved
      in the formation of a new chimaeric transcription factor. Both patients shared
      several poor prognostic factors at presentation and an adverse clinical course.
      The t(3;17)(q23;q21) translocation may therefore predict a poor outcome in ALL.

PMID- 8857951
TI  - Detection of microsatellite markers in leukaemia using DNA from archival bone
      marrow smears.
AB  - We describe a simple PCR method to detect highly polymorphic repetitive DNA
      markers (microsatellites) in leukaemia using DNA from fresh and archival bone
      marrow smears. Neither the period of storage nor staining of the slides affected
      microsatellite PCR. Comparison of slide DNA with constitutive DNA from buccal
      epithelium revealed loss of heterozygosity (LOH) with at least one marker in four
      of 11 leukaemias. Marrow smears offer an attractive archival source of DNA for
      the detection of microsatellite markers. Applications include detection of LOH or
      tracing the origin of cell populations, e.g. in bone marrow transplant
      recipients.

PMID- 8857952
TI  - CMV infection after allogeneic bone marrow transplantation is associated with the
      occurrence of various autoantibodies and monoclonal gammopathies.
AB  - Recent findings indicate that the kinetics of B-cell reconstitution after marrow
      transplantation mimic normal ontogeny. The early B-cell repertoire during
      ontogeny is characterized by a high degree of autoreactivity and
      interconnectivity. Therefore, in a prospective analysis, 95 consecutive
      recipients of an allogeneic marrow transplant were screened for the occurrence of
      various autoantibodies and 47 of these 95 were also screened for monoclonal
      gammopathies. None of the patients developed antibodies specific for systemic
      autoimmune disorders. In contrast, a high prevalence of natural antibodies
      (79/95) was found early post-transplant, with 58 of these 79 patients developing
      two or more autoantibodies. According to multiple regression, the mean number of
      natural antibodies (95% confidence limits in parentheses) depends significantly
      (P = 0.006) on the status of CMV infection: 0.9 (0.4; 1.6) CMV-negative: 2.0
      (1.0; 3.3) asymptomatic CMV infection; 3.1 (1.7; 5.0) CMV disease. Sex, age,
      underlying disease, conditioning therapy, acute graft-versus-host disease and CMV
      serology of donor and recipient pretransplant did not affect the number of
      natural autoantibodies. Monoclonal gammopathies were detected in 12/47 patients
      with a predominance of the IgG-kappa subtype. All these 12 patients suffered from
      a viral infection (CMV, n = 11: influenza strain A, n = 1). The high degree of
      self-reactivity post-transplant further supports the hypothesis that B-cell
      reconstitution mimics ontogeny. Moreover, these data indicate nonspecific
      polyclonal, CMV-mediated, presumably T-cell independent B-cell stimulation and
      disturbed T-cell regulatory function following allogeneic BMT.

PMID- 8857953
TI  - Characterization of platelet-reactive antibodies in children with varicella
      associated acute immune thrombocytopenic purpura (ITP).
AB  - Biochemical analyses were performed on blood samples obtained from two children
      (P1, P2) who presented with acute immune thrombocytopenic purpura (ITP) following
      a recent varicella zoster virus (VZV) infection. Patient sera had antibodies that
      were reactive with normal blood-group O platelets as measured by flow-cytometric
      assay. Western blot analysis of electrophoretically separated normal blood-group
      O platelets under reducing and non-reducing conditions demonstrated that these
      sera were reactive with platelet antigens of approximately 50 and approximately
      110 kD, respectively. These 50/110 kD antigens were not reactive with seven sera
      from acute ITP patients whose illness was not preceded by VZV infection, with
      serum from a patient with a prior history of VZV and no thrombocytopenia, nor
      with normal healthy control sera. VZV antibodies (IgG and IgM), isolated from
      patient sera by affinity chromatography using immobilized purified VZV
      glycoproteins, were found to bind to gel-filtered autologous platelets and with
      normal blood-group O platelets, as analysed by flow cytometry. No binding was
      observed using antibodies similarly prepared from healthy volunteer sera. To
      investigate their ability to sensitize platelets to complement activation,
      affinity-purified VZV antibodies were incubated with platelets and then with
      purified complement components C1 and 125 I-labelled C4. Platelets reacted with
      VZV-specific antibodies from the two patients and showed increases of 2.3-2.4
      fold of platelet-surface deposition of 125 I-C4b, compared to controls. These
      data provide evidence that virus-specific antibodies occurring in children with
      varicella-associated acute ITP cross-react with normal platelet antigens, and may
      contribute to platelet clearance.

PMID- 8857954
TI  - Autoantibodies and anti-mouse antibodies in thrombocytopenic patients as assessed
      by different MAIPA assays.
AB  - Two MAIPA (monoclonal antibody [MAb] immobilization of platelet antigen) assays
      were performed to determine (a) autoantibodies to platelet glycoproteins (GP) and
      (b) serum antibodies recognizing mouse MAbs used in the assay. In MAIPA I,
      control platelets were incubated simultaneously with human serum and a mouse MAb
      to a platelet glycoprotein (GP IIb-IIIa, Ib-IX, Ia-IIa, IV and p24). In MAIPA II,
      the control platelets were incubated first with the human serum and then, after
      washing, with the selected mouse MAb. A series of 25 patients with autoimmune
      thrombocytopenic purpura (ATP) associated or not with other autoimmune states
      were examined. Autoantibodies (both MAIPA I and MAIPA II positive) or anti-mouse
      Abs (MAIPA I positive and MAIPA II negative) were frequent in both groups of
      patients. Statistically significant differences existed in the incidence of anti
      mouse Abs between patients (56.5%) and healthy donors (10%). This suggests that
      their production may be related to thrombocytopenias associated with autoimmune
      disease. We speculate that the presence of anti-mouse antibodies could reflect an
      abnormality in the immunological modulation of the idiotypic network.

PMID- 8857955
TI  - The epitope specificity of heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is caused by antibodies (HIT-Abs) that
      bind to a complex of heparin and platelet factor 4. We investigated the epitope
      specificity of the HIT-Abs, and found that the HIT-Abs recognized solid-phase
      immobilized complexes with an optimum ratio of four to eight molecules of PF4 per
      molecule of heparin. To try to define the epitopes within the PF4 molecule,
      intact and reduced (linearized) PF4 was tested against 29 different sera from
      patients with HIT. In addition, eight different peptides that spanned the PF4
      molecule were studied for their ability to bind to the HIT-Abs either alone or in
      the presence of heparin. With the exception of a subpopulation of patient samples
      (5/29, 17%), we found that reduced PF4 and the peptides were uniformly non
      reactive with the HIT-Abs in the presence of heparin. Reduced PF4 and PF4 carboxy
      terminal peptides with a minimum size of 19 amino acids were recognized by a
      minority (5/29) of HIT-Abs samples but only when heparin was present. The
      specificity of this subgroup of samples from patients with HIT was highly
      restricted and the loss of one amino acid (peptide reduced in length from 19 to
      18 amino acids) rendered the peptides non-reactive. The clinical characteristics
      of these patients were similar to the other HIT patients. These studies
      demonstrate that the majority of HIT-Abs recognize a noncontiguous conformational
      epitope on the PF4 molecule that is produced when four to eight PF4 molecules are
      bound together by heparin.

PMID- 8857956
TI  - Endothelial cell surface actin serves as a binding site for plasminogen, tissue
      plasminogen activator and lipoprotein(a).
AB  - One of the mechanisms by which endothelial cells (ECs) regulate fibrinolysis is
      through the regulated assembly of proteins such as plasminogen, tissue
      plasminogen activator (tPA) and urokinase (uPA) on their membrane surface.
      Receptors for many of these fibrinolytic factors have been isolated and
      characterized. A unique 45 kD plasminogen receptor present on ECs derived from
      vein vasculature has been identified and resolved into two plasminogen binding
      components. One component consists of the unique 45 kD plasminogen receptor (pI =
      6.3) whereas the other component (pI = 5.1) is identified as the cytoskeletal
      protein, actin. Immunofluorescent studies of isolated ECs confirm the presence of
      actin on their extracellular surface. This observation is consistent with a
      number of other recent reports of actin externally localized on other cell types.
      In vitro studies using purified actin confirm that plasminogen binds to actin
      both saturably and with relatively high affinity. Competition studies with lysine
      indicated that the binding was largely kringle-dependent, and when binding of tPA
      to actin was assessed, it also bound to actin with 70-80% of binding inhibited by
      lysine. Lipoprotein (a), which shows homology with plasminogen, also interacted
      with actin. Addition of plasminogen and low-density lipoproteins inhibited Lp(a)
      binding to actin in a dose-dependent fashion. Moreover, in competition with tPA,
      partial inhibition of plasminogen binding to actin was also observed. In
      experiments using anti-actin antibodies added in excess to cultured ECs, binding
      of plasminogen was inhibited by 45%, tPA binding was inhibited by 46% and Lp(a)
      binding was reduced by 56%, confirming actin as a binding site for these various
      ligands whilst attesting to the presence of other EC receptors for these
      proteins. Collectively, the data presented are consistent with actin playing a
      major role in localizing binding not only of plasminogen, but also of tissue
      plasminogen activator and Lp(a) to the surface of human endothelial cells.

PMID- 8857957
TI  - Activated protein C inhibits thrombus formation in a system with flowing blood.
AB  - We studied the effect of increasing concentrations of protein C (PC) and
      activated protein C (APC) on haemostasis in an in vitro thrombosis model. Blood
      from healthy donors was anticoagulated with citrate-phosphate-dextrose (final
      citrate concentration 19 mM) or a low molecular weight heparin (LMWH, 20 IU/ml).
      Enzymatically denuded rabbit aorta segments were exposed to flowing blood for 10
      min in an annular perfusion chamber. PC and APC were added to the perfusate
      immediately prior to exposure. In citrated blood at a shear rate of 800/s, PC and
      APC induced a statistically significant decrease in platelet deposit at 16
      micrograms/ml and 32 micrograms/ml. In perfusions performed with blood
      anticoagulated with LMWH, there was no effect on platelet deposition at 16 and 32
      micrograms/ml either at shear rates of 300/s or 800/s. Addition of PC showed no
      effect on fibrin deposition at a shear rate of 300/s; in contrast, a
      nonstatistically significant 40% reduction was seen at a shear rate of 800/s,
      compared to controls. Addition of APC caused a 100% reduction in fibrin formation
      at 16 and 32 micrograms/ml at both shear rates studied. PC and APC inhibited
      platelet deposition on the exposed subendothelial surface, in a dose-dependent
      manner. Effects of PC and APC on platelet function might be mediated through
      inhibition of thrombin generation at the platelet microenvironment.

PMID- 8857958
TI  - A common frameshift mutation in von Willebrand factor does not alter mRNA
      stability but interferes with normal propeptide processing.
AB  - Quantitative defects in von Willebrand factor (VWF) result in type 1 and type 3
      von Willebrand disease (VWD). This study characterizes the defect in VWF
      expression resulting from a single nucleotide deletion in VWF exon 18, a mutation
      previously reported to be common among type 3 VWD patients. A severely affected
      (type 3) VWD patient in the current pedigree is homozygous for the mutation,
      whereas heterozygous individuals exhibit variable expression of type 1 VWD. In
      contrast to the previously reported high frequency of the exon 18 deletion in
      Sweden and Germany, this mutation appears to be infrequent among type 3 VWD
      patients in the United States. Although this frameshift mutation results in
      proximal premature termination of VWF translation, the abnormal VWF mRNA is
      stable. The mutant truncated recombinant VWF protein is retained within the
      transfected cell, and no propeptide processing is observed, suggesting a defect
      in protein folding. Cotransfection of mutant and wild-type recombinant VWF fails
      to demonstrate a dominant effect of the mutant on the normal allele. Consistent
      with these results, plasma VWF propeptide of the homozygous individual was
      markedly reduced whereas heterozygotes exhibited moderately reduced levels. In
      contrast to type 2A VWD (group 1), the misfolded mutant protein does not appear
      to exert a dominant-negative effect on normal VWF subunits expressed from the
      wild-type allele.

PMID- 8857959
TI  - Soluble L-selectin in the connective tissue diseases.
AB  - Plasma levels of the leucocyte adhesion molecule L-selectin were measured by
      ELISA in 41 patients with rheumatoid arthritis, 18 with ankylosing spondylitis,
      18 with systemic sclerosis and 27 with vasculitis together with 42 age- and sex
      matched controls. Low levels of soluble L-selectin were found in systemic
      sclerosis (797 +/- 302 ng/ml, P < 0.05) and vasculitis (941 +/- 329 ng/ml, P <
      0.05) relative to controls (1244 +/- 269 ng/ml). The exact reasons for low levels
      of soluble L-selectin are unclear, but may reflect reduced shedding from
      leucocytes and/or strong binding to its cell membrane ligand(s). An approximate
      inverse relationship between soluble L-selectin and disease severity may have
      clinical relevance.

PMID- 8857960
TI  - Epistaxis in anticoagulated patients: educating an at-risk population.
AB  - Epistaxis is a common problem amongst anti-coagulated patients. Application of
      first-aid principles can control the majority of bleeds. In our sample of 60
      patients attending the anticoagulant clinic, 40% were unable to think of a single
      measure that would be helpful in controlling a nose bleed. 6 weeks after being
      given first-aid advice the proportion of patients able to recall at least three
      first-aid principles had improved from 8% to 50%. First-aid education in this
      respect was well received and there was a good recall rate. Provision of advice
      verbally backed up by a printed sheet gave best rates of recall.

PMID- 8857961
TI  - Large-scale DNA typing for human platelet alloantigens by PCR-PHFA (preferential
      homoduplex formation assay).
AB  - Alloimmunization against human platelet alloantigens (HPA) is known to be
      involved in disorders such as neonatal alloimmune thrombocytopenic purpura,
      posttransfusion purpura, and refractoriness to platelet transfusion therapy. HPA
      typing is essential in diagnosis and management of patients. Therefore a reliable
      and speedy method is necessary for HPA typing. We have successfully applied a new
      DNA typing method, PCR-preferential homoduplex formation assay (PHFA) method, to
      typing for the HPA-1, -2, -3, -4, -5 and -6 systems. This method is based on DNA
      strand competition during hybridization under a precisely controlled temperature
      gradient between a double-labelled amplicon (standard DNA), prepared from biotin-
      and DNP-labelled primers, and an unlabelled amplicon (sample DNA). The results
      obtained by PCR-PHFA typing were in good agreement with the allotypes determined
      by serological typing and by other DNA typing methods. The PCR-PHFA method can be
      easily automated, is suitable for typing both small and large numbers of samples,
      and thus is applicable to routine HPA typing.

PMID- 8857962
TI  - High prevalence of autoimmune phenomena in hepatitis C virus antibody positive
      patients with lymphoproliferative and connective tissue disorders.
AB  - The aim of this study was to investigate whether hepatitis C virus (HCV) may
      perturb the immune system towards autoreactivity. We studied the relationship
      between the prevalence of anti-HCV and the presence of laboratory and/or clinical
      autoimmune features in 300 patients: lymphoid malignancies (167) and autoimmune
      disorders (connective tissue diseases 100; idiopathic thrombocytopenic purpura
      (ITP) 33). As a control, hepatitis B surface antigen (HBV) and anti-hepatitis B
      core antigen (anti-HBc) were related to the same parameters. Anti-HCV and anti
      HBV were detected in 68/300 (22.6%) and 70/300 (24.6%) patients, respectively.
      HCV prevalence was 18% in lymphoproliferative disorders (anti-HBc 28.1%) and 26%
      in connective tissue disease (anti-HBc 16.3%). Among ITP cases, 12/33 (36.4%)
      were anti-HCV+ and 10/33 (30.3%) anti-HBc+. In 24/30 (80%) anti-HCV+ patients
      with lymphoproliferative disorders at least one serologic or clinical autoimmune
      abnormality was detected. To the contrary, only 10/45 (22.2%) anti-HBc+ patients
      with lymphoproliferative disorders had at least one serologic or clinical
      abnormality (P < 0.0001). A statistically significant correlation was observed
      between HCV prevalence and the number of autoimmune alterations in both
      lymphoproliferative and connective tissue disorders, which was not found for anti
      HBc. These data suggest that HCV may skew the immune system toward the production
      of autoantibodies and also support the possibility that some cases of ITP may be
      linked to both HCV and HBV infection.

PMID- 8857963
TI  - Myelodysplastic syndrome in childhood.

PMID- 8857964
TI  - ICE, mini-ICE or high-dose hydroxyurea to mobilize Philadelphia (Ph1)-negative
      PBPC in chronic myelogenous leukaemia.

PMID- 8857965
TI  - Effects of steroids on acute myeloblastic leukaemia.

PMID- 8857966
TI  - A critique of the picture archiving and communication system at the Hammersmith
      Hospital, London, U.K.

PMID- 8857967
TI  - Computed tomography of retroperitoneal and mesenteric sarcomas: a pictorial
      essay.
AB  - Retroperitoneal and mesenteric sarcomas are rare tumours that often do not
      present until they are very large. Computed tomography (CT) is helpful for
      diagnosis and for planning therapy. This pictorial essay illustrates the spectrum
      of CT manifestations of these tumours that the authors have encountered and
      includes a review of the various aspects of clinical presentation and treatment.

PMID- 8857968
TI  - Tear of the distal biceps tendon presenting as an antecubital mass: magnetic
      resonance imaging appearances.
AB  - OBJECTIVE: To present the magnetic resonance imaging (MRI) findings for tear of
      the distal biceps tendon presenting as a soft-tissue mass in the antecubital
      fossa. PATIENTS AND METHODS: The authors identified four patients who had been
      referred for MRI of an antecubital soft-tissue mass and in whom a tear of the
      distal biceps tendon was found. RESULTS: All four patients had typical MRI
      findings for a tear of the distal biceps tendon. In three, a tear at the
      insertion of the tendon onto the radial tuberosity was associated with small
      fluid collections at the site of the tear. In one patient there was thinning of
      the tendon and fluid within the tendon sheath. The diagnosis was confirmed by
      clinical correlation and follow-up of at least 1 year (in two patients) or by
      surgical exploration (in two). CONCLUSIONS: With knowledge of the MRI appearance
      of distal biceps tendon tear, it should be possible to correctly diagnose the
      problem, even when the clinical presentation does not suggest the diagnosis.

PMID- 8857969
TI  - Discoid meniscus in children: magnetic resonance imaging characteristics.
AB  - OBJECTIVE: To describe the magnetic resonance imaging (MRI) appearance and
      associated abnormalities of discoid menisci in children. PATIENTS AND METHODS:
      The MRI findings for a total of 30 knees (in 20 children ranging in age from 4.5
      to 16 [mean 9] years) in which discoid meniscus had been diagnosed were reviewed
      and correlated with clinical symptoms and arthroscopy findings. RESULTS: The
      symptoms, bilateral in 5 patients and unilateral in 15, included pain in 15
      knees, snapping or clunking in 8, reduced mobility in 8, locking in 2 and "giving
      way" in 2; there were flexion contractures in 2 patients. Five patients had
      unilateral symptoms but bilateral discoid menisci. The transverse diameter of the
      meniscus ranged from 18 to 37 mm and the depth from 14 to 36 mm. The lateral
      meniscal height was significantly greater than the medial meniscal height (p =
      0.0001). On T1-weighted and T2-weighted images the meniscal signal was increased
      heterogeneously in 11 knees, in a central, horizontal, linear fashion in 9,
      diffusely in 6 and in a partly linear, partly diffuse fashion in 3. Thirteen
      joint effusions, 10 lateral meniscal tears and 4 meniscal cysts were identified.
      Eight arthroscopy procedures were performed in six of the children (for seven
      knees). Discoid meniscus was confirmed in six knees (with one initial false
      negative result), tears were confirmed in four, and an additional tear was
      identified in one; in addition, one meniscus was characterized as Wrisberg type.
      CONCLUSIONS: Discoid meniscus commonly occurs bilaterally. High intrameniscal
      signal is found, especially in symptomatic patients. The size criteria for
      diagnosing this condition in children are similar to those for adults.

PMID- 8857970
TI  - Comparison of colour Doppler imaging with conventional duplex scanning in the
      evaluation of extracranial carotid stenosis.
AB  - OBJECTIVE: To assess the concordance between conventional duplex scanning and
      colour Doppler imaging in the grading of extracranial carotid artery stenosis.
      PATIENTS AND METHOD: A total of 67 carotid bifurcations in 48 patients were
      studied independently by two observers. First, each observer obtained a
      conventional duplex scan and recorded peak systolic and diastolic velocities.
      Then, each observer performed a colour Doppler study in which only the point of
      maximal colour shift was sampled. The stenosis in each case was subsequently
      classified, first as one of four classes (mild, moderate, severe or critical) on
      the basis of percent stenosis and peak systolic and diastolic velocities, and
      then as one of two groups (less than 70% or 70% or greater, with a peak systolic
      velocity of 2.3 m/second as the cut-off point). RESULTS: For the first observer,
      the two methods disagreed in 10 (15%) of the 67 cases. In five of these cases,
      colour Doppler imaging indicated a higher class of stenosis, and in the other
      five cases conventional duplex scanning indicated a higher class of stenosis. For
      this observer, the mean of the difference between conventional duplex and colour
      Doppler scanning for peak systolic and diastolic values was not statistically
      different from 0 (three-way analysis of variance). With colour Doppler imaging
      observer 1 detected all of the 14 cases of stenosis of 70% or greater that were
      detected by conventional duplex scanning. For observer 2, the results of the two
      methods differed in 12 (18%) of the 67 cases. For all 12 cases, conventional
      duplex scanning indicated a higher class of stenosis. The mean of the difference
      between the two methods was -23.8 cm/second (standard deviation 46.0) for peak
      systolic velocity and -10.7 cm/second (standard deviation 24.7) for peak
      diastolic velocity (both significantly different from 0). With colour Doppler
      imaging observer 2 did not identify 3 of the 16 cases of stenosis of 70% or
      greater that were detected by conventional duplex scanning. CONCLUSION:
      Discrepancies may exist between conventional duplex scanning and colour Doppler
      imaging in assessing extracranial carotid artery stenosis.

PMID- 8857971
TI  - Intracranial gas: a pictorial essay.
AB  - Intracranial gas is a common finding on postcraniotomy computed tomography scans.
      It can also be found in a wide variety of other benign and life-threatening
      clinical settings. Because intracranial gas is never normal, its presence must be
      explained. This pictorial essay describes the imaging features of intracranial
      gas and demonstrates the findings for many of the causes of this condition.

PMID- 8857972
TI  - Bilateral spontaneous dissecting aneurysm of the internal carotid arteries:
      report of two cases.
AB  - Spontaneous dissection (dissecting aneurysm) of the internal carotid artery is a
      common cause of ischemic stroke in young patients. Very infrequently, dissecting
      aneurysm of the internal carotid artery occurs bilaterally. This paper presents
      two such cases and discusses in detail variations in the time of occurrence, the
      angiographic characteristics and possible predisposing factors.

PMID- 8857973
TI  - Spinal metastases as a first presentation of malignant astrocytoma.
AB  - A 46-year-old man presented with low dorsal pain and paresthesia. Computed
      tomography showed an osteolytic lesion involving most of the vertebral body and
      the left pedicle of the 12th thoracic vertebra (T12). Contrast-enhanced magnetic
      resonance imaging (MRI) of the spine showed an enhancing soft-tissue mass that
      involved the T11 and T12 vertebral bodies, as well as that of the first lumbar
      vertebra; the mass caused cord compression. Another lesion was identified at T9.
      The findings of percutaneous needle aspiration biopsy of the lesion were
      consistent with metastatic astrocytoma, a diagnosis confirmed at surgery. MRI of
      the brain showed an asymptomatic lesion of the left temporal lobe; histologic
      confirmation of malignant astrocytoma was obtained by stereotactic biopsy. This
      report shows that metastatic bone disease secondary to malignant astrocytoma may
      manifest itself before the primary lesion becomes symptomatic. This presentation
      of astrocytoma was unusual because there were no symptoms of the intracranial
      tumour and because metastatic disease to the bones is less common than to the
      chest and the lymph nodes.

PMID- 8857974
TI  - High-attenuation mucous plugging in allergic bronchopulmonary aspergillosis.
AB  - OBJECTIVE: To assess the prevalence of high-attenuation mucous plugs observed on
      chest computed tomography (CT) scans in patients with allergic bronchopulmonary
      aspergillosis. PATIENTS AND METHODS: The CT scans of 14 patients with allergic
      bronchopulmonary aspergillosis, seen between July 1990 and July 1994 at a single
      tertiary-care institution, were reviewed. The presence and distribution of high
      attenuation mucous plugs were recorded in each case. RESULTS: High-attenuation
      mucous plugs were present in 4 (28%) of the 14 patients. Mucous plugging was
      unilobar in three of these four patients. Mucous plugging with attenuation
      similar to that of chest wall muscle was not found in any of the patients with
      high-attenuation plugging. CONCLUSIONS: High-attenuation mucous plugs occur in
      approximately one quarter of patients with allergic bronchopulmonary
      aspergillosis and may be more common in patients with unilobar plugging.

PMID- 8857975
TI  - Residents' corner. Answer to case of the month #40. Hypertension caused by left
      renal reninoma.

PMID- 8857976
TI  - Residents' corner. Answer to case of the month #41. Mature ovarian cystic
      teratoma.

PMID- 8857977
TI  - The value (and limitations) of surgical rate variation analysis.

PMID- 8857978
TI  - To freeze or not to freeze.

PMID- 8857979
TI  - Devolution of hip and knee replacement surgery?

PMID- 8857981
TI  - Radiology for the surgeon. Case 11. Presentation. Midgut volvulus.

PMID- 8857980
TI  - Neurilemoma of the ulnar nerve.

PMID- 8857982
TI  - Surgical rates in subprovincial areas across Canada: rankings of 39 procedures in
      order of variation.
AB  - OBJECTIVE: To rank 39 surgical procedures in order of variation of inpatient
      surgical rates, according to a new index of variation and to test the hypothesis
      that there is greater variation for primarily discretionary operations than for
      primarily non-discretionary operations. DESIGN: A population-based retrospective
      cohort study. SETTING: Nine provinces (99.19% of Canada's population).
      PARTICIPANTS: All hospital inpatients who underwent any of 39 types of surgery
      and were separated from hospital between Apr. 1, 1988 and Mar. 31, 1990 (the most
      recent time period for which Canada-wide data were available at the subprovincial
      level analysed). MAIN OUTCOME MEASURE: Rankings of the 39 procedures according to
      the index of variation, calculated from inpatient surgery rates in 255 census
      divisions across Canada. RESULTS: The 13 procedures with the greatest variation
      were all primarily discretionary. Thirteen of the 14 procedures with the lowest
      variation were primarily non-discretionary. All but one of the procedures whose
      degree of discretion was deemed intermediate were in the middle third of the
      rankings. CONCLUSIONS: The greatest variation is found in primarily discretionary
      operations. Further investigation should be focused on identified geographical
      locations where rates for operations that are primarily discretionary are
      unusually high or low, and particularly on those operations for which there is
      disagreement regarding the indications for surgery.

PMID- 8857983
TI  - Quality-of-life assessment: recent trends in surgery.
AB  - A literature review conducted for a 1989 article on assessing the quality of life
      in surgical studies revealed that quality of life was more often mentioned than
      measured. Few authors reported the use of known, standardized scales. The
      objective of this study was to determine if and to what extent this situation has
      changed. A MEDLINE search of surgical studies published between 1989 and 1995
      produced over 277 abstracts of surgical studies containing the words "quality of
      life." The abstracts were studied in three time periods: 1989-1990, 1991-1992 and
      1993-1995. Findings indicated that the use of the term "quality of life"
      increased markedly over the study period, and studies using standardized measures
      escalated from 27.4% in 1989-1990 to 48.3% in 1993-1995. Those abstracts not
      stating how quality of life was assessed decreased from 48.4% in the early period
      to 21.7% in the last period. Of the abstracts reporting studies that used quality
      of life measures, 33% came from cancer studies, 21.7% from cardiovascular or
      respiratory studies, 14.8% from gastroenterology studies, 13.4% from nephrology
      studies and 6.1% from orthopedic studies. Surgical investigators selected a
      variety of global measures of quality of life as well as disease-specific
      instruments. The abstracts also revealed that surgeons are using quality-of-life
      assessment to monitor patients over time, to help select patients for surgery, to
      determine the effect of surgical treatment and for making policy decisions.
      Notwithstanding the limitations of this project, there is evidence in the
      literature that surgeons are increasingly willing to assess the impact of the
      surgical interventions by quality-of-life measures and are becoming more familiar
      with the diverse measures used to assess quality of life.

PMID- 8857984
TI  - Devolution of hip and knee replacement surgery?
AB  - The objectives of this study were to assess trends in referral patterns for joint
      replacements (JRs) in Ontario between the fiscal year 1988/89 and the fiscal year
      1993/94; to assess the redistribution of financial resources if services were
      provided to residents in the region where they reside; and to estimate the
      financial implications of the devolution of primary JRs from tertiary-care
      hospitals to community hospitals. Despite rapid growth in the provision of JRs,
      there was no significant change in their regional distribution. Community
      hospitals have increased their share of JRs at the expense of teaching hospitals.
      For hospitals located in Central east Ontario, the cost of providing JRs to
      nonresidents increased from $ 5.9 million in 1988/89 to $8.3 million in 1993/94.
      Devolution of primary JRs requires a minimum reallocation sum of $25.1 million,
      with potential cost savings of $4.3 million. Many obstacles limit the devolution
      and local provision of health care services, including modifications to referral
      patterns and the availability of provider expertise, especially when a
      substantial redistribution of resources is required. Better clinical data to
      evaluate outcomes and better patient-specific costing data are required.
      Devolution of services should be addressed in the context of appropriate
      institutional compensation for medical education.

PMID- 8857985
TI  - Establishment and cost analysis of an office surgical suite.
AB  - The objective of this study was to show that minor operative procedures done in a
      nonhospital setting can be provided more efficiently than those done in hospital
      and are agreeable to both patient and surgeon. A description of the facility,
      equipment required and types of procedures that can be performed provides a guide
      for other surgeons who may wish to establish an office surgical suite. The senior
      author's experience from 1993 to 1995 is described. Costs were compared on a
      procedure basis from financial data obtained from the practice and from a local
      400-bed community hospital. Experience shows that patients are receptive to
      undergoing minor procedures outside the traditional hospital setting. An office
      surgical suite allows the surgeon greater flexibility in work scheduling, thereby
      improving productivity. The cost per case appears to be less in the office than
      in the hospital for the particular costs identified. The current method of
      funding minor surgical procedures provides an incentive to the surgeon to perform
      these procedures in hospital, because the individual practitioner is not
      responsible for any operating expenses. Thus, if costs are to be reduced and
      quality maintained, funding mechanisms must be reformed to allow less costly
      service to evolve.

PMID- 8857986
TI  - Minimally invasive cardiac surgery for removal of the greater saphenous vein.
AB  - OBJECTIVE: To determine if saphenous vein required for coronary bypass could be
      quickly, easily and safely removed with a minimally invasive technique. DESIGN: A
      consecutive series. SETTING: A university centre. MATERIAL AND METHODS: In
      cadavers, a standard mediastinoscope was used to remove segments of the greater
      saphenous vein. Thigh segments, superior leg segments and ankle segments were
      removed. Fifteen minutes were allowed for removal of a segment. RESULTS: Segments
      of vein 15 to 17 cm long could be removed. One segment could not be removed
      within 15 minutes. Thigh segments were easy to remove, calf segments were the
      most difficult. There were no avulsed side branches. All incisions were less than
      5 cm long. CONCLUSIONS: Saphenous vein can be harvested quickly and safely by a
      minimally invasive method. Lower extremity complications may be reduced and long
      term patency improved with this in-situ technique of vein removal.

PMID- 8857987
TI  - The cementless anatomic medullary locking femoral component: an independent
      clinical and radiographic assessment.
AB  - OBJECTIVE: To review the clinical performance of the anatomic medullary locking
      (AML) femoral stem in total hip arthroplasty. DESIGN: A clinical and radiographic
      review. SETTING: A tertiary lower limb joint replacement centre. PATIENTS: Two
      hundred and twenty-one patients with noninflammatory gonarthrosis. INTERVENTIONS:
      Two hundred and twenty-seven primary total hip arthroplasties with the
      noncemented AML component completed by two surgeons. MAIN OUTCOME MEASURES:
      Independent review by two experienced reviewers of the postoperative Harris hip
      score, radiographs of component fixation, size and degree of diaphyseal fill.
      RESULTS: Harris hip score was 84 (range from 43 to 98); component fixation showed
      bone ingrowth in 41%, stable fixation with fibrous ingrowth in 56% and unstable
      fixation in 3%; severe thigh pain in 4% of cases correlated with unstable
      fixation, and there was mild thigh pain in 20% of cases. CONCLUSION: The AML
      femoral stem performs well in replacement arthroplasty compared with other
      noncemented stems.

PMID- 8857988
TI  - Interpretation by radiologists of orthopedic total joint radiographs: is it
      necessary or cost-effective?
AB  - OBJECTIVE: To examine the necessity and cost-effectiveness of interpretation by
      radiologists of orthopedic radiographs obtained for patients who undergo total
      hip or knee replacement. DESIGN: A prospective study. Serial preoperative and
      postoperative x-ray films of the joint in patients scheduled to undergo total hip
      or knee joint replacement during one calendar year were interpreted by both
      radiology and orthopedic department staff and compared. Intraoperative findings
      were used to confirm the radiologic interpretation. The follow-up was 1 year.
      SETTING: A university teaching hospital. INTERVENTIONS: Primary or revision total
      hip or knee replacement. MAIN OUTCOME MEASURES: Differences in interpretation of
      radiographs by radiologists and orthopedic surgeons for any of the four
      procedures. A change in orthopedic management. RESULTS: For preoperative
      radiographs, there were no discrepancies between the radiologists and orthopedic
      surgeons with respect to primary joint replacement. For 100 revision procedures
      there were 15 discrepancies, but in all cases the orthopedic surgeon's
      interpretation proved to be correct. For the postoperative radiographs, there
      were no discrepancies in the group of revision hip replacements. For the other
      three groups there were a total of six discrepancies and in all cases the
      orthopedic surgeon's interpretation was correct. In two cases conditions were
      present that were not recognized by staff from either the radiology department or
      orthopedic department. CONCLUSION: Interpretation by radiologists of total joint
      radiographs in patients who undergo primary or revision total hip or knee
      replacement arthroplasty is not necessary or cost-effective.

PMID- 8857989
TI  - Magnesium in cardioplegia: is it necessary?
AB  - OBJECTIVE: To study the effectiveness of magnesium in cardioplegic solution in
      preventing postoperative arrhythmias and perioperative ischemia. DESIGN:
      Randomized, control study. SETTING: The cardiovascular surgery division of a
      major referral centre for the maritime provinces of Canada. PATIENTS: Fifty
      patients scheduled to undergo coronary artery bypass who had a normal ejection
      fraction, normal preoperative serum magnesium level and no history of atrial or
      ventricular arrhythmia were randomized into two groups of 25 patients. One group
      received magnesium sulfate (15 mmol/L) in the cardioplegic solution (group 1),
      the other (control) group did not receive magnesium sulfate in the cardioplegic
      solution (group 2). INTERVENTION: Coronary artery bypass grafting during which
      myocardial protection was provided by intermittent cold blood cardioplegia.
      OUTCOME MEASURES: Postoperative serum magnesium levels, cardiac-related death,
      infarction and arrhythmias. RESULTS: All group 2 patients had a lower
      postoperative serum magnesium level than group 1 patients. There were no cardiac
      related deaths in either group. More group 2 patients had ischemic
      electrocardiographic changes than group 1 patients (p < 0.03). Non-Q wave
      myocardial infarction occurred in two patients (one in each group). Eight
      patients in group 2 had atrial fibrillation compared with five patients in group
      1. Ventricular ectopia occurred significantly (p < 0.01) more frequently in group
      2 than in group 1. CONCLUSION: The addition of magnesium to the cardioplegic
      solution is beneficial in reducing the incidence of perioperative ischemia and
      ventricular arrhythmia in patients who undergo coronary bypass grafting.

PMID- 8857990
TI  - Cryosurgery for malignant tumours of the liver.
AB  - OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided cryosurgery
      to treat malignant tumours of the liver. DESIGN: A prospective nonrandomized
      trial. The follow-up was complete and ranged from 8 to 35 months. SETTING: A
      university-affiliated hospital. PATIENTS: Ten patients with secondary malignant
      tumours of the liver; 1 with primary hepatoma. INTERVENTIONS: Computed
      portography for preoperative staging; laparotomy and ultrasonographic examination
      of the liver; cryosurgical ablation of liver tumours with or without a
      concomitant resection. Thirteen procedures were performed on 11 patients. MAIN
      OUTCOME MEASURES: Preoperative morbidity, disease-free and overall survival.
      RESULTS: Of 24 lesions frozen, the procedure on 4 lesions was considered a
      technical failure because of persistent disease. There were no perioperative
      deaths. One patient had a liver abscess that resolved with percutaneous drainage.
      One patient had a biliary fistula that resolved spontaneously, and one had a
      transient rise in the serum creatinine level. Of 11 patients treated, 7 had a
      recurrence in the liver (persistent disease in 2 and new liver metastases in 5);
      2 of these patients died. One patient died of distant disease with no local
      recurrence. At the time of writing, one patient was alive with extrahepatic
      disease and no local recurrence and two were free of disease. CONCLUSIONS:
      Cryosurgery of the liver is a relatively safe procedure that allows treatment of
      otherwise unresectable malignant disease. Proof of long-term benefit requires
      further experience and follow-up.

PMID- 8857991
TI  - Synovial chondromatosis of the metacarpophalangeal joint: case report and review
      of the literature.
AB  - Intra-articular synovial chondromatosis in the hand is rare but should be
      considered in the differential diagnosis of a swollen, stiff or painful joint.
      Other possible diagnoses include osteoarthritis, rheumatoid arthritis, gout,
      trauma and chronic infection, and unless enchondral ossification of loose bodies
      is seen the diagnosis of synovial chondromatosis may not be made preoperatively.
      A 69-year-old man with synovial chondromatosis of the metacarpophalangeal joint
      is reported. The joint was swollen and tender. He had not sustained trauma and
      there was no evidence of arthritis, involvement of other joints or infection.
      Complete synovectomy with removal of all loose bodies was successful and his
      symptoms resolved. Intra-articular synovial chondromatosis is a benign condition,
      but spontaneous resolution is the exception and surgical synovectomy remains the
      most effective treatment.

PMID- 8857992
TI  - Recurrent superior mesenteric artery (Wilkie's) syndrome: a case report.
AB  - Superior mesenteric artery syndrome (SMAS) is a rare condition. The diagnosis is
      usually made by exclusion. A previously healthy 20-year-old woman who had
      recurrent SMAS is described. Diagnosis of the condition was difficult. Initially,
      small-bowel enteroclysis, upper gastrointestinal series and endoscopy, biopsy of
      gastric and duodenal mucosa, abdominal computed tomography (CT) and
      ultrasonography were used to make the diagnosis. Abdominal CT suggested
      pancreatitis causing compressive obstruction of the superior mesenteric artery.
      Conservative management was helpful at first, but cramping and projectile emesis
      recurred. Upper gastrointestinal series suggested duodenal distension and a
      filling defect in the region of the superior mesenteric artery. Repeat endoscopy
      showed a lateral pulsatile compression in the region of the distal duodenum and
      SMAS was diagnosed. Medical therapy was not helpful so duodenojejunostomy was
      carried out. The operation was successful and the patient was symptom-free for 1
      year, when the syndrome recurred, with symptoms of periumbilical pain,
      intermittent episodes of vomiting and loose stools. At reoperation the
      duodenojejunal anastomosis was found to be displaced to the left of the superior
      mesenteric artery pedicle causing recurrent obstruction. The duodenojejunostomy
      was converted to a Roux-en-Y duodenojejunostomy. The patient has since remained
      well. A MEDLINE search of the literature for the period 1961 to October 1994
      revealed that there were no reported cases of a recurrence of SMAS in an
      otherwise healthy adult patient. In spite of the difficulty in diagnosing this
      condition, heightened awareness can lead to early diagnosis and avoid unnecessary
      suffering for the patient.

PMID- 8857993
TI  - Does evaluation of medical students produce any positive feedback?

PMID- 8857994
TI  - Sir William Hingston.
AB  - Sir William Hingston was one of Canada's most illustrious surgeons in the second
      half of the 19th century. Not only was he a very innovative surgeon but he was an
      excellent teacher and wrote many medical articles during a career that spanned
      over 50 years. Active as he was medically, he found time to serve a term as mayor
      of Montreal and was on the board of directors of various banks and companies. As
      recognition of his many talents, he was knighted by Queen Victoria in 1895. He
      died in 1907 at the age of 78 years.

PMID- 8857995
TI  - Surgical rate variation analysis.

PMID- 8857996
TI  - Alternative management for post-thoracotomy pain syndrome.

PMID- 8857997
TI  - Monitoring patients in the intensive care unit after carotid endarterectomy.

PMID- 8857998
TI  - The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis.
AB  - This paper attempts to put together in the form of a flow sheet (Fig. 1) the
      several known alterations, both chemical and structural, of brain tissue in
      Alzheimer disease, which ultimately result in dementia. While most investigators
      in the field believe strongly that amyloid deposition is at the core of the
      disease, this writer finds that a more coherent, and thus more satisfying, schema
      can be based on the centrality of cytoskeletal abnormality. Not only do all four
      identified genes interact one way or another with the cytoskeleton, but
      abnormality of the latter leads to alterations of the Golgi apparatus with
      effects on protein processing, and on axoplasmic flow such that one can expect
      loss of synapses and subsequent loss of neurons with consequent disconnection and
      loss of neurotransmitters. Dementia is the result.

PMID- 8857999
TI  - Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67
      proliferation indices.
AB  - p16 is involved in a cell-cycle regulatory cascade that includes cyclin-dependent
      kinase 4 (cdk4), cyclin D1 and pRb. Alterations of each of these components have
      been described in primary human glioblastoma multiforme (GBM) or GBM cell lines,
      and alterations of the individual components of this pathway appear inversely
      correlated with one another. While this suggests that disruption of any
      individual component has similar oncogenic effects, homozygous deletions of the
      CDKN2/p16 gene are the most common genetic alteration. We investigated the
      relationship between homozygous CDKN2/ p16 deletions and cellular proliferation
      in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma, 15 grade II
      astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a
      comparative multiplex PCR assay, homozygous deletions of the CDKN2/p16 gene were
      detected in 5 anaplastic astrocytomas (25%) and 6 GBMs (46%), but in none of the
      lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of
      proliferating cells in the same samples used for molecular genetic analysis. In
      both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were
      significantly higher in tumors with CDKN2/p16 deletions (20%) than in those
      without deletions (10%; p = 0.0001). These results suggest that homozygous
      CDKN2/p16 deletions in high-grade astrocytomas may have a more deleterious effect
      on cell cycle control than the other aberrations in the p16-cdk4-cyclin D1-pRb
      pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions
      are more common genetic events in high-grade astrocytomas than RB mutations or
      CDK4 amplification.

PMID- 8858000
TI  - Stereological analysis of cerebral atrophy in human immunodeficiency virus
      associated dementia.
AB  - Brain atrophy is a common finding in patients with AIDS, but the relationship of
      atrophy to HIV-associated dementia is unclear. We used unbiased, stereological
      methods on postmortem brain specimens to estimate volumes of different brain
      regions in patients prospectively diagnosed with and without HIV-associated
      dementia. Thirty HIV-seropositive (9 without AIDS/without dementia, 6 with
      AIDS/without dementia, 15 with AIDS/with dementia) and 7 HIV-seronegative
      controls were studied using the technique of point counting and Cavalieri's
      principle of volume estimation. There was a significant reduction in the mean
      neocortical volume (15%, p = 0.032) in the group with AIDS when compared to the
      seronegative controls, and this difference was accentuated when comparing only
      the group with HIV-associated dementia to the seronegatives (neocortex: 18%, p =
      0.020). There were no significant differences between the AIDS groups with and
      without HIV-associated dementia, although there was a trend for smaller volumes
      in the most severely demented patients. There were no differences in white matter
      volumes between groups. In conclusion, patients dying with AIDS and particularly
      those with HIV-associated dementia, show significant neocortical atrophy when
      compared to seronegative controls. The lack of a significant difference in
      cerebral atrophy between HIV-seropositive patients with and without dementia
      suggests that atrophy may be a more generalized phenomenon of AIDS as opposed to
      a specific marker for HIV-associated dementia.

PMID- 8858001
TI  - Profiles of neuronal thread protein expression in Alzheimer's disease.
AB  - Neuronal thread proteins (NTPs) comprise a family of molecules expressed in brain
      and primitive neuroectodermal tumor cell lines. In Alzheimer's disease (AD),
      increased CNS levels of the 21 kD NTP species are correlated with dementia. The
      present study characterizes the nature and distribution of NTP expression using
      recently generated brain-derived polyclonal and monoclonal antibodies (MoAbs) to
      recombinant AD7c-NTP protein. In AD, high levels of NTP immunoreactivity were
      detected in neuronal perikarya, neuropil fibers, and white matter fibers (axons).
      In addition, 4 of the 23 AD7c-NTP MoAbs labeled degenerating neurons (with or
      without neurofibrillary tangles), axonal spheroids, dystrophic neurites, or
      irregular, wavy threadlike neuropil fibers in AD. Increased neuronal AD7c-NTP
      immunoreactivity in AD colocalized with perikaryal accumulations of tau-1,
      phosphorylated neurofilament, and the ganglioside, A2B5. In addition, AD7c-NTP
      immunoreactivity was detected in early neuritic plaques along with beta-amyloid
      containing fibrils, but not in mature plaques, nor was it colocalized in beta A4
      immunoreactive fibrils. This study demonstrates the profiles of NTP
      overexpression in relation to paired helical filament-associated
      neurodegenerative lesions in AD.

PMID- 8858002
TI  - Identification of phosphorylation sites in PHF-TAU from patients with Guam
      amyotrophic lateral sclerosis/parkinsonism-dementia complex.
AB  - Guam Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (Guam ALS/PDC)
      is a progressive neurodegenerative disorder characterized by abundant
      neurofibrillary tangles (NFTs) composed of aggregated paired helical filaments
      (PHFs). These abnormal filaments resemble the PHFs in neurofibrillary lesions of
      classic Alzheimer's disease (AD), and recent studies demonstrated that tau in
      Guam ALS/PDC is aberrantly phosphorylated and biochemically similar to the
      abnormal tau proteins (PHFtau) in classic AD. However, unlike PHFtau in AD, there
      is little information on the specific sites of phosphorylation in PHFtau from
      Guam ALS/PDC. Thus, to address this important issue, we examined tangle-rich Guam
      ALS/PDC and AD brains by Western blot, immunoelectron microscopy and
      immunohistochemistry using 13 antibodies to defined phosphate-dependent or 
      independent epitopes distributed throughout AD PHFtau. These studies identified 7
      previously unknown sites of phosphorylation in PHFtau from Guam ALS/PDC (i.e.
      Thr181, Thr231, Ser262, Ser396, Ser404, Ser422, and the site defined by
      monoclonal antibody AT10), all of which also are found in AD PHFtau. Indeed, the
      Western blot, light and immunoelectron microscopic data suggest that NFTs, PHFs
      and PHFtau in Guam ALS/PDC are very similar to their counterparts in classic AD.
      Thus, insights into mechanisms leading to the accumulation of neurofibrillary
      lesions in Guam ALS/PDC may advance understanding of the pathogenesis and
      biological consequences of these lesions in classic AD.

PMID- 8858003
TI  - Distribution of immunoglobulin superfamily members ICAM-1, -2, -3, and the beta 2
      integrin LFA-1 in multiple sclerosis lesions.
AB  - To identify potential molecular substrates for leukocyte trafficking and
      activation in multiple sclerosis (MS) brain, we determined the immunocytochemical
      distribution of the beta, integrin lymphocyte-function-associated antigen-1 (LFA
      1) and its major ligands, intercellular adhesion molecule (ICAM)-1, ICAM-2, and
      ICAM-3 in MS tissue. Colocalization of these adhesion molecules with lineage
      specific markers was analyzed by dual-labeling immunocytochemistry and confocal
      microscopy. ICAM-1 and ICAM-2 were detected on endothelial cells, and ICAM-3
      immunoreactivity was restricted to infiltrating leukocytes. In control brain, 10%
      of glucose transporter-1 positive vessels contained ICAM-1 immunoreactivity on
      their luminal surface and 21% were ICAM-2-positive. A significant increase in
      ICAM-1-positive vessels was found in MS brains. This increase was greater in MS
      lesions (81% of vessels) than in nonlesion areas (37% of vessels). A significant
      increase in ICAM-1-positive vessels was found in encephalitis (55% of vessels)
      but not in Parkinson's (17% of vessels) brains. The percentage of vessels
      expressing ICAM-2 was not increased in MS, encephalitis, or Parkinson's brains.
      Both ICAM-3 and LFA-1 were detected on the vast majority of infiltrating
      lymphocytes and monocytes in and near MS lesions, and these cells were often
      closely apposed to each other. In addition, LFA-1 was detected on activated
      microglia located close to the edge of demyelinating lesions. ICAM-3-positive
      leukocytes were often closely apposed to LFA-1-positive microglia. These results
      suggest a role for ICAM-1, -2, and LFA-1 in the transendothelial migration of
      leukocytes into MS brain and a role for ICAM 3/LFA-1 interactions in the
      activation of lymphocytes, monocytes, and microglia in MS lesions.

PMID- 8858004
TI  - Distribution of beta-amyloid precursor and B-cell lymphoma protooncogene proteins
      in the rat retina after optic nerve transection or vascular lesion.
AB  - The expression of beta-amyloid precursor protein (APP) and B-cell lymphoma
      protooncogene protein (Bcl-2) in retinal cells in the rat was studied using
      immunocytochemistry at different times after intraorbital optic nerve transection
      or vascular lesion. Three hours to one month after transection of the optic
      nerve, a significant increase in APP and Bcl-2 immunostaining was observed in
      retinal Muller glia but not in retinal neurons. In contrast, injury to blood
      vessels that supply the eye without cutting the optic nerve resulted in a
      complete loss of APP and Bcl-2 immunostaining in Muller cells and an increase in
      immunoreactivity in distinct populations of retinal neurons. The overall pattern
      of APP immunostaining in Muller cells and neurons was essentially the same as
      that of Bcl-2 under identical experimental conditions. These results suggest that
      the expression of APP and Bcl-2 in retinal cells is dependent on the nature and
      severity of injury, and that rapid and common mechanisms are involved in
      regulating the expression of these molecules.

PMID- 8858005
TI  - Inflammation, A beta deposition, and neurofibrillary tangle formation as
      correlates of Alzheimer's disease neurodegeneration.
AB  - We evaluated entorhinal cortex and superior frontal gyrus for hallmarks of
      Alzheimer's disease (AD) pathology, including inflammation, in three patient
      sets: AD patients, nondemented elderly patients with few or no neurofibrillary
      tangles (NFTs) and amyloid beta peptide (A beta) deposits, i.e. normal controls
      (NC), and nondemented elderly patients with profuse entorhinal cortex NFTs and
      neocortical A beta deposits, i.e. high pathology controls (HPC). Membrane attack
      complex (C5b-9) immunoreactivity and immune activation of microglia (MHCII
      expression) were used as general markers for inflammation. Compared to NC
      patients, AD patients exhibited significant cortical synapse loss, A beta
      deposition, NFT formation, and inflammation. HPC patients also had significantly
      elevated A beta deposition and NFT formation, but there was no evidence of
      synapse loss and little or no evidence of inflammation. Across patients and brain
      regions the measures of inflammation each accounted for significant percentages
      of the variance in synaptophysin immunoreactivity and each was more highly
      correlated with synapse estimates than NFT formation or A beta deposition.

PMID- 8858006
TI  - Familial amyotrophic lateral sclerosis with a two base pair deletion in
      superoxide dismutase 1: gene multisystem degeneration with intracytoplasmic
      hyaline inclusions in astrocytes.
AB  - We performed a comparative neuropathological study on two siblings with familial
      amyotrophic lateral sclerosis (FALS). The clinical course of the sister who died
      at age 46 was 18 months, and that of the brother who died at age 65, 11 years.
      The neuropathological findings of the female were compatible with FALS with
      posterior column involvement. Her brother had multisystem degeneration in
      addition to the motor neuron disturbance; Lewy body-like hyaline inclusions
      (LBHIs) were present in the affected neurons of the degenerative lesions.
      Eosinophilic inclusions were seen in many astrocytes of the affected areas of the
      male FALS patient. Immunohistochemical assays revealed that most astrocytic
      inclusions reacted with the antibodies against Cu/Zn-superoxide dismutase 1
      (SOD1) and ubiquitin; immunoreactivity was essentially the same as that of the
      neuronal LBHIs. Ultrastructurally the astrocytic inclusions were composed mainly
      of 15- to 25-nm granule-coated fibrils and granular material, resembling LBHIs of
      the neurons. Despite the dissimilar neuropathological features, both patients had
      the same two base pair deletion in exon 5 of the SOD1 gene. These findings
      suggest that FALS due to an SOD1 gene mutation is potentially a multisystem
      degenerative disorder, affecting not only neurons, but also astrocytes.

PMID- 8858007
TI  - Recommendations for the preferred future of nursing.

PMID- 8858009
TI  - Outcomes of an adjunct executive appointment for faculty.
AB  - The Council on Graduate Education for Administration in Nursing (CGEAN) was
      established to further develop and improve graduate education for administration
      in nursing. The Council seeks to identify the nature and direction of education
      for administration in nursing in various healthcare systems, providing guidelines
      for programs offering administration. A major goal of CGEAN is facilitating
      dialogue between nursing service administrators and graduate level educators who
      are engaged in teaching and research related to administration in nursing. This
      column, sponsored by the members of the Council, analyzes and responds to
      position statements and trends related to the delivery of health services and
      graduate education for administrators in nursing.

PMID- 8858010
TI  - Development of a nurse executive decision support database. A model for outcomes
      evaluation.
AB  - It is increasingly more important that nurse executives systematically evaluate
      innovations and changes in nursing practice and management. To plan effectively,
      data elements that are most appropriate for decision making must be identified
      and strategies for data collection and analysis must be formulated. The author
      describes a model in which an identifiable group of clinical, fiscal, quality,
      productivity, and care provider variables serve as data for baseline and later
      comparative evaluations.

PMID- 8858011
TI  - Nurse relationships and work group disruption.
AB  - As nursing administrators and managers respond to healthcare reform pressures
      with downsizing, rightsizing, and work group reorganization, they need to pay
      attention to and support the nursing work group relationships. A study of 908
      registered nurses (RNs) in a variety of nursing work environments in four
      hospitals indicates that interpersonal relationships are an important part of job
      satisfaction, that there is a relationship between some types of work group
      disruption and RN satisfaction with interpersonal relationships, and that there
      is a relationship between work group disruption and RN perceptions of patient
      safety/quality of care.

PMID- 8858012
TI  - Developing nurse leaders for today and tomorrow. Part 2, Implementing a model of
      leadership for community-based practice.
AB  - In part 1 of this two-part series, the authors described the Manager as Developer
      Model and its use in acute care settings and a community-based nursing
      administration curriculum. In this article, they predict its use to guide
      development of leadership and education for the future of community-based
      practice.

PMID- 8858013
TI  - Results-oriented committee restructuring.
AB  - Identifying delays in accomplishing key initiatives and maintaining competent
      staff in an environment of decision-making chaos and bureaucracy, nursing leaders
      created an environment of change that was more controlled, with greater input
      from the staff who would have to implement these changes in their clinical
      practice. Creative committee restructuring in the nursing department has been
      recognized institutionally as a model for cost-effective utilization of staff,
      prompt attention to current issues, and expediting change. The authors discuss
      how they redesigned committee structure, solicited using multidisciplinary
      forums, and created a decentralized mechanism for staff participation.

PMID- 8858014
TI  - The Patient Self-Determination Act. The chief nurse executive's perspective.
AB  - Ensuring patient autonomy in the medical treatment process, particularly in
      decisions involving death and dying made a major stride with the implementation
      of the Patient Self-Determination Act in 1991. Compliance with the act was not
      difficult in terms of providing information and education for patients and
      providers. However, role comfort for professional staff, as well as complex
      issues involving the activation process, still are of major concern. The author
      reports 4 years of implementation experience of chief nurse executives.

PMID- 8858015
TI  - "Sepsis/SIRS," physiologic classification, severity stratification, relation to
      cytokine elaboration and outcome prediction in posttrauma critical illness.
AB  - OBJECTIVE: To develop a quantitative severity stratification within the framework
      of a Physiologic State Classification (PSSC) system that can be applied to
      critically ill post-trauma patients with "sepsis/SIRS" and to relate PSSC to the
      nature of the plasma cytokine response. MATERIALS AND METHODS: At each study time
      period, a patient was classified into one of seven physiologic States previously
      derived from clustering 17 cardiopulmonary and metabolic variables from 338
      critically ill patients: R = reference, A = normal stress response, B = metabolic
      insufficiency, C1 (early) and C2 (late) = respiratory insufficiency, D =
      cardiogenic insufficiency, H = nonshock hypovolemia. MAIN RESULTS: The PSSC used
      State data from a developmental set of 159 trauma patients in a logistic model
      (L2PDEATH) to provide a quantitative index of severity. This severity index was
      tested on 80 new trauma patients (mean injury Severity Score (ISS) = 27.6, 64%
      survivors). Using PSSC State distributions for evaluation of enzyme-linked
      immunosorbent assay (ELISA) measured cytokines interleukin (IL)-1, IL-6, IL-8,
      tumor necrosis factor (TNF) showed the multicytokine score to be greatest in
      those C2- and B-State regions associated with a higher severity as measured by
      L2PDEATH. Compared with ARDEATH of the Acute Physiology and Chronic Health
      Evaluation (APACHE) II scoring system, L2PDEATH provided a better indicator of
      severity of sepsis/systemic inflammatory response syndrome (SIRS) for posttrauma
      patients. CONCLUSIONS: PSSC allows classification of the physiologic and cytokine
      mediator response to trauma and permits stratification of severity in posttrauma
      critical illness.

PMID- 8858016
TI  - Physiologic stability and physiologic state.
AB  - Several disease states (e.g., disseminated inflammation) demonstrate physiologic
      stability: they resolve only slowly and are resistant to both specific and
      symptomatic therapies. The existence of multiple stable physiologic states,
      including both health and disease states, is not anticipated by classical, linear
      descriptions of physiologic control mechanisms. Multiple stable states are,
      however, predicted by a simple nonlinear model in which the resistance to
      perturbation derives from interconnections among the model's elements. If the
      stability of selected disease states derives from nonlinear interactions among
      cells, tissues, and organs, then some therapies aimed at supporting or
      normalizing performance of specific organs may be misdirected.

PMID- 8858017
TI  - Intraoperative end-tidal carbon dioxide levels and derived calculations
      correlated with outcome in trauma patients.
AB  - BACKGROUND: To determine the relationship between the prognosis of seriously
      injured patients requiring emergency surgery and intraoperative end-tidal CO2
      variables and "excess Pco2." METHOD: Retrospective chart review of 100 seriously
      injured patients admitted to Detroit Receiving Hospital and requiring major
      surgery (mortality rate of 40%). Standard intraoperative monitoring, including
      continuous capnography, plus arterial blood analyses every 15 to 30 minutes
      during surgery. RESULTS: After resuscitation for 45 to 90 minutes, 11 patients
      had a systolic blood pressure < 100 mm Hg and, of these patients, 10 (91%) died.
      Of the remaining 89 patients, mortality rates were 53% (16/30), with an end-tidal
      CO2 of 22 mm Hg or less, versus 24% (14/59) with an end-tidal CO2 of 23 mm Hg or
      more (p = 0.011). An arterial to end-tidal Pco2 difference of 13 mm Hg or more
      after resuscitation was associated with an increased mortality rate (50% (20/34
      vs. 18% (20/55)) (p < 0.005). The mortality rate was particularly high, with a
      final arterial to end-tidal Pco2 difference of 12 mm Hg or more (73% (30/41)
      versus 17% (10/59) (p < 0.001). A final Paco2 excess (i.e., the amount by which
      the Paco2 was higher than expected from the bicarbonate) > 1.0 mm Hg was also
      associated with an increased mortality rate ((62% (33/53) vs. 15% (7/47)) (p <
      0.001). CONCLUSION: Values derived from the end-tidal CO2 and the excess Pco2
      should be monitored intraoperatively in critically injured patients. Efforts
      should be made to improve cardiac output and adjust ventilation to maintain an
      end-tidal Pco2 of 25 mm Hg or more, an arterial to end-tidal CO2 difference of 12
      mm Hg or less, and an excess Paco2 of 1.0 mm Hg or less.

PMID- 8858018
TI  - Effect of cyclo-oxygenase inhibition on in vitro B-cell function after burn
      injury.
AB  - The role of PGE2 in suppression of B-cell function after burn injury was
      investigated. Splenocytes from burned or sham-burned mice were isolated 8 days
      after burn injury and cultured with lipopolysaccharide with or without the
      addition of prostaglandin E2 (PGE2) or indomethacin (Indo). Anti-peptidoglycan
      polysaccharide immunoglobulin (Ig)M (specific antibody to a bacterial antigen),
      total IgM, and total IgG levels in culture supernatant and lymphocyte
      proliferation were measured. All B-cell functions were significantly suppressed
      by burn injury. PGE2 suppressed all B-cell functions except for IgG synthesis.
      Indo restored anti-peptidoglycan polysaccharide IgM to normal levels, but did not
      have a significant effect on suppressed proliferation and total IgM synthesis.
      IgG synthesis was increased by PGE2 and inhibited by Indo. Although not all B
      cell suppression was accounted for by PGE2, this prostaglandin appeared to be a
      mechanism responsible for impaired antigen specific antibody response and isotype
      switching. Successful restoration of specific antibody synthesis to bacterial
      antigen suggests a potential therapeutic role for a cyclo-oxygenase blocking
      agent after burn injury.

PMID- 8858019
TI  - Fluid resuscitation attenuates early cytokine mRNA expression after peritonitis.
AB  - OBJECTIVE: To study the hypothesis that fluid resuscitation alters cytokine gene
      expression after experimental murine peritonitis. MATERIALS AND METHODS: Mice
      underwent cecal ligation and puncture (CLP) to induce peritonitis and were
      randomized to receive variable amounts of normal saline (0, 0.25, 1.0 ml.
      subcutaneously) and serum (0 or 0.1 mL) after operation. Hepatic and small
      intestinal (ileal) tissue were harvested at 3 or 6 hours after CLP, and total
      tissue RNA was extracted. Reverse transcriptase polymerase chain reaction was
      used to provide relative quantitation of tumor necrosis factor-alpha and
      interleukin (IL)-1 beta messenger RNA (mRNA) compared with beta-actin. RESULTS:
      CLP without resuscitation resulted in significant increases in hepatic tumor
      necrosis factor-alpha mRNA (1190% at 6 hours compared with normal animals), and
      IL-1 beta mRNA (1475%), and intestinal IL-1 beta mRNA (1243%). Volume
      administration attenuated cytokine expression at both 3 and 6 hours, and saline
      seemed to have more potent effects than serum. The volume of resuscitation
      correlated with survival at 18 hours. Survival in the saline (1 mL) + serum group
      was 90% at 18 hours compared with 20 to 40% in the groups with little or no
      resuscitation. Overall, there were no survivors at 30 hours. CONCLUSIONS: Fluid
      resuscitation (amount, composition, timing) should be an important consideration
      in the utilization of experimental infection models. Furthermore, optimization of
      the patient's intravascular volume status during sepsis may have important
      effects on immune responses, in addition to improving hemodynamic variables.

PMID- 8858020
TI  - Depressed osteoblast activity and increased osteocyte necrosis after closed bone
      fracture and hemorrhagic shock.
AB  - BACKGROUND: Although bone fracture and hemorrhagic shock are frequent
      complications in trauma patients, it remains unknown whether hemorrhagic shock
      after bone fracture produces any deleterious effects on osteoblast function and
      osteocyte necrosis. METHODS: Sham-operation, closed bone fracture (right tibia)
      with and without hemorrhagic shock (mean arterial blood pressure 35 +/- 5 mm Hg
      for 90 minutes followed by fluid resuscitation) were induced in 18 male C3H/HeN
      mice (25 g body weight) At 72 hours after the experiment, all animals were
      killed, whole blood was obtained by cardiac puncture, and plasma assayed for
      circulating levels of osteocalcin. RESULTS: Plasma osteocalcin levels were found
      to be significantly depressed after closed bone fracture in conjunction with
      hemorrhagic shock. Closed bone fracture alone increased plasma osteocalcin.
      Histologic analysis of the fracture sites revealed that hemorrhagic shock after
      closed bone fracture significantly increased osteocyte necrosis adjacent to the
      fracture site, when compared to animals with closed bone fracture alone.
      CONCLUSIONS: These findings suggest that severe hemorrhage after closed bone
      fracture depresses osteoblast activity and increases osteocyte necrosis, which
      should compromise fracture healing under those conditions.

PMID- 8858021
TI  - Role of platelet-activating factor antagonism in posthemorrhage septic shock in
      pigs.
AB  - OBJECTIVES: To study the role of platelet-activating factor (PAF) antagonism in
      posthemorrhage septic shock in pigs. DESIGN: Experimental study. MATERIALS AND
      METHODS: Twelve anesthetized pigs were bled, kept with a mean arterial pressure
      of 30 mm Hg for 30 minutes, and then resuscitated with 50 mL/kg of isotonic
      saline. A continuous infusion of Escherichia coli endotoxin 36 micrograms/kg/hour
      was given intravenously for 3.5 hours starting 30 minutes after resuscitation.
      The animals were divided into two groups of six each. One group received I mg/kg
      of BB-882 (a potent specific PAF receptor antagonist) as a bolus during
      resuscitation, followed by a continuous infusion of BB-882 1 mg/kg/hour. The
      other group received vehicle alone. MEASUREMENTS AND MAIN RESULTS: The measured
      variables were blood temperature, heart rate, intravascular pressures, cardiac
      output, systemic and pulmonary vascular resistance, lung-thorax compliance, blood
      gases, hemoglobin oxygen saturation, packed cell volume and blood sugar and serum
      lactic acid concentrations. The group treated with BB-882 had significantly
      higher intracardiac pressures and cardiac output, and had less increase in
      systemic vascular resistance. The BB-882 group had significantly less lactic
      acidemia than the control group (p < 0.05, analysis of variance appropriate for
      repeated measurement design). BB-882 had no effect on endotoxin-induced hypoxia
      or reduced lung-thorax compliance. CONCLUSIONS: PAF antagonism reduced the
      increase in systemic vascular resistance, improved cardiac output, and reduced
      lactic acidemia in posthemorrhage septic shock in pigs, but it did not improve
      hypoxia or reduced lung-thorax compliance.

PMID- 8858022
TI  - Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric
      oxide in porcine endotoxic shock.
AB  - BACKGROUND: Nitric oxide synthase (NOS) inhibition has been shown to potentiate
      lipopolysaccharide (LPS) associated pulmonary hypertension, which may worsen
      right ventricular (RV) dysfunction and decrease cardiac output during sepsis.
      This study evaluates whether inhaled nitric oxide can ameliorate the adverse
      cardiopulmonary effects of NOS inhibition during endotoxemia. METHODS: After an
      infusion of Escherichia coli LPS (200 micrograms/kg), animals were resuscitated
      with saline (1 mL/kg/min) and observed for 3 hours while mechanically ventilated
      (FIO2, 0.6; VT, 12 mL/kg; positive end-expiratory pressure, 5 cm H2O). The LPS
      group (n = 6) received no additional treatment. The N-nitro-L-arginine methyl
      ester (NAME) group (n = 5) received L-NAME, a NOS inhibitor, 50 micrograms/kg/min
      for the last 2 hours. The NO+NAME group (n = 6) received inhaled NO (40 ppm) and
      L-NAME for the last 2 hours. The control group (n = 5) received only saline
      without LPS. Hemodynamic data and blood gases were collected hourly for 3 hours.
      RESULTS: L-NAME worsened LPS-associated pulmonary hypertension and RV dysfunction
      as reflected by decreased RV ejection fraction. Inhaled nitric oxide
      significantly decreased pulmonary hypertension and improved RV ejection fraction
      and stroke work index. There were no adverse systemic effects. CONCLUSIONS:
      Inhaled nitric oxide reverses pulmonary hypertension seen with L-NAME treatment
      during endotoxemia and may be a useful adjunct to NOS inhibition in the treatment
      of septic shock.

PMID- 8858023
TI  - Role of calcium in lipopolysaccharide-stimulated tumor necrosis factor and
      interleukin-1 signal transduction in naive and endotoxin-tolerant murine
      macrophages.
AB  - OBJECTIVE: Dysregulated macrophage cytokine production may predispose to organ
      failure during sepsis. Macrophages pretreated in vitro with low-dose endotoxin
      (LPSp) become "tolerant" to subsequent lipopolysaccharide (LPS) activation
      (LPSa), characterized by inhibition of tumor necrosis factor (TNF) and
      augmentation of interleukin-1 (IL-1). To understand cytokine dysregulation we
      examined the Ca2+ dependence of TNF and IL-1 signal transduction to LPSa and
      whether it was altered by LPSp. METHODS: Murine peritoneal exudate macrophages
      received +/- 100 ng/mL of LPSp for 24 hours. Cultures were pretreated for 2 hours
      with specific signal transduction inhibitors (verapamil, a Ca2+ channel
      inhibitor; TMB-8, an inhibitor of intracellular Ca2+ release; U73122, an
      inhibitor of phospholipase C; or W7, a calmodulin inhibitor) before 24 hours LPSa
      stimulation. TNF and IL-1 mRNA were estimated 6 hours after LPSa by using reverse
      transcriptase polymerase chain reaction. Supernatant TNF and IL-1 were measured
      by bioassay. RESULTS: Treatment with verapamil, TMB-8, U73122, or W7 markedly
      inhibited TNF release by LPSa, but had little effect on IL-1 release.
      Reprogramming by LPSp did not alter the Ca2+ signal transduction pathways for
      either cytokine. U73122 and verapamil did prevent the augmentation of IL-1
      release seen after LPSp. TNF message was present after LPSa despite reprogrammed
      inhibition of TNF protein by LPSp. Signal transduction inhibitors that blocked
      Ca2+ altered TNF and IL-1 message in reprogrammed macrophages in a pattern
      similar to their effects on naive cells. CONCLUSIONS: Intracellular Ca2+ is
      required for TNF protein release by naive macrophages and TNF mRNA transcription
      of both naive and LPSp reprogrammed cells, however LPSa-stimulated IL-1 release
      in peritoneal macrophages does not require Ca2+ dependent signaling pathways.

PMID- 8858024
TI  - Elevated selectin levels after severe trauma: a marker for sepsis and organ
      failure and a potential target for immunomodulatory therapy.
AB  - Severe injury is frequently complicated by sepsis and organ failure. Activated
      neutrophils adherent to inflamed endothelia have been implicated in the
      pathogenesis of these complications. Identification of high-risk patients to
      target immunomodulatory therapy, however, remains an elusive goal. We postulated
      that (1) patients at risk for sepsis and organ failure could be identified by
      measuring shed selectin adhesions molecules as a marker of endothelial activation
      after injury and reperfusion, and (2) these elevated selectin levels would
      correlate with injury severity, shock, major complications, and mortality.
      METHODS: Blood samples were drawn from 50 patients with multiple trauma every 2
      hours after admission for the first 24 hours, and every 6 hours for the
      subsequent 24 hours, and assayed for levels of shed E- and P-selectin. Patients
      were then stratified according to Injury Severity Score (ISS), presence or
      absence of shock, presence or absence of organ failure and/or infectious
      complications, and finally, death versus survival. RESULTS: Trauma patients who
      had ISS < 30, who did not develop shock, sepsis, or organ dysfunction, had
      minimal increase in circulating E- and P-selectin over admission levels. In
      patients who subsequently developed infectious complications, organ dysfunction,
      or both, or subsequently went on to die, elevated levels of E-selectin levels
      were evident by 36 hours, and in some cases, earlier. Differences between
      nonsurvivors and survivors was statistically significant. There was also a trend
      toward increased levels of P-selectin in the same group of patients, although
      these differences were not significant. There was no differentiation in either of
      the two selections when patients were stratified according to ISS or presence of
      shock. CONCLUSION: A subset of major trauma patients manifest increased levels of
      circulating E-selectin adhesion molecules after resuscitation. These patients
      seem to be at increased risk of death and possibly at risk for infections
      complications and organ failure. Selectin blockade is a potential new
      immunomodulatory strategy in this subgroup of patients.

PMID- 8858025
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances pulmonary
      defenses against pneumococcal infections after splenectomy.
AB  - BACKGROUND: Splenectomized individuals are at risk for pneumococcal sepsis.
      Alveolar macrophage bactericidal function is depressed after splenectomy.
      Granulocyte-macrophage colony-stimulating factor (GM-CSF) has pronounced effects
      on the number and function of macrophages. We hypothesized that GM-CSF treatment
      could improve alveolar macrophage bactericidal activity against pneumococci, and
      improve survival with pneumococcal infection. METHODS: Two weeks after
      splenectomy or sham operation, mice were treated with GM-CSF or saline twice
      daily for varying times. Alveolar macrophages were obtained by bronchopulmonary
      lavage, and bactericidal activity was measured. Survival was assessed after
      pneumococcal aerosol challenge. RESULTS: Alveolar macrophage bactericidal
      activity was improved with GM-CSF treatment in both eusplenic and asplenic mice
      (p < 0.001). GM-CSF treatment improved survival in both groups (p < 0.001).
      CONCLUSIONS: GM-CSF can augment alveolar macrophage function and provide
      protection against pneumococcal infections. It may be a useful adjuvant therapy
      for normal and splenectomized individuals.

PMID- 8858027
TI  - Air-powered guns: too much firepower to be a toy.
AB  - OBJECTIVE: This study reviews our experience and calls attention to the potential
      danger of air-powered guns. DESIGN: Retrospective analysis. MATERIALS AND
      METHODS: Review of patients with air-powered gun-injuries admitted to a Level I
      trauma center and air gun deaths reported to the United States Consumer Product
      Safety Commission over a 5-year period ending July 1994. RESULTS: Sixteen
      children (median age 10) were admitted after sustaining BB or pellet gun
      injuries. Three children had cranial penetration; one remains severely brain
      impaired. One of two thoracic injuries required left ventriculorrhaphy. All five
      children sustaining abdominal wounds underwent laparotomy for enteric
      perforations; one was complicated by an intra-arterial pellet embolus. Three of
      five children with neck wounds had penetrating tracheal injury. Overall nine
      children required operative intervention. No deaths occurred in our series, but
      there were 33 air gun deaths reported to the United States Consumer Product
      Safety Commission during this period. CONCLUSION: Our data demonstrate that
      injuries from air-powered guns should be treated in a manner similar to those
      from low velocity powder firearms. We can no longer continue to underestimate the
      potential for life-threatening injury from these weapons.

PMID- 8858026
TI  - Epidemiology and prevention of severe assault and gun injuries to children in an
      urban community.
AB  - OBJECTIVES: To describe the epidemiology of severe assault and gun injuries to
      children in an urban population and consider the impact of a comprehensive injury
      prevention program. MATERIALS AND METHODS: Pediatric injury deaths and hospital
      admissions for Northern Manhattan (1983-1992) were linked to census counts to
      compute incidence. Poisson regression was used to compare trends in incidence of
      assault and gun injuries before and during a community-wide pediatric injury
      prevention program in Central Harlem. MAIN RESULTS: The incidence of severe
      nonfatal assault injury was 60.94/100,000/year, 10 times the fatality rate. The
      incidence of all gun injuries was 31.13. In adolescence, guns were the leading
      cause of both fatal and severe nonfatal assault injury, and were the most lethal
      method of assault (case-fatality = 18.5% for gun vs. 1.2% for all non-gun assault
      injury). Rates of assault and gun injuries declined by nearly 50% in the
      intervention community, while they increased in a neighboring community.
      CONCLUSIONS: Comprehensive interventions may be effective in curbing the
      incidence of severe assault injuries to urban youth. Further controlled
      evaluations are needed to confirm the effectiveness of programs such as this and
      to better understand the prevention of violent injuries.

PMID- 8858028
TI  - Compelling evidence for discretionary brain computed tomographic imaging in those
      patients with mild cognitive impairment after blunt trauma.
AB  - OBJECTIVE: To identify computed tomographic-detected intracranial hemorrhage
      (CTIH) risk factors and outcome in mild cognitive impairment (MCI) blunt trauma
      patients. METHODS: In 2,587 consecutive patients, 251 (9.7%) had CTIH. RESULTS:
      Analysis is on 2,252 direct transports with 163 CTIH, because transfers were
      different (7.2 vs. 26.3%, p < 0.0001). CTIH rates for patients age 14-60 and > 60
      years were 6.3 and 15.9%, p = 0.001. In those 14-60 years (n = 2,032), CTIH (n =
      128) was independently related to arrival Glasgow Coma Scale (GCS) score and
      cranial soft tissue injury (CSTI) (p = 0.0001). [table: see text] Craniotomy was
      < or = 0.6% in each group except GCS score of 13 with CSTI, 7.4%. Of those with
      CTIH, 98.4% survived. Of those at low risk (GCS score of 14 without CSTI and GCS
      score of 15), 1,504 had no CTIH. Of these, 64.4% were available for serial
      cognitive evaluation (noncranial injuries mandated hospitalization; tracheal
      intubation was not required). In those > 60 years (n = 220), CTIH (n = 35) was
      independently related to GCS and CSTI (p = 0.003). CTIH for GCS score of 15
      without CSTI was 5.8%, but > or = 16% for others. One craniotomy was required. Of
      those with CTIH, 91.4% survived. CONCLUSIONS: In mild cognitive impairment
      patients triaged directly to a Level I trauma center, age, arrival GCS score, and
      cranial soft tissue injury are risk factors for CT-detected intracranial
      hemorrhage. Neurologic deterioration and death are infrequent. These data
      strongly suggest that observation and discretionary brain CT imaging are a
      rational approach for blunt-injury mild cognitive impairment.

PMID- 8858029
TI  - Arterial-jugular vein free amino acid levels in patients with head injuries:
      important role of glutamine in cerebral nitrogen metabolism.
AB  - Traumatic brain injury is the single largest contributor of trauma center deaths.
      Injury to the brain cannot be considered as an isolated event, affecting only
      this organ. Profound hypoglutaminemia commonly seen in patients with head
      injuries may be caused by the diminished release of glutamine from the brain to
      the systemic circulation. To assess this hypothesis, we have simultaneously
      measured the free amino acid (AA) levels in systemic arterial (A, radial artery),
      cerebral venous (JV, jugular bulb), and systemic venous (PA, pulmonary artery)
      plasma in 11 adult patients with severe head injuries once within 48 hours of the
      initial injury before starting nutritional support and again after 3 to 4 days of
      enteral feeding. Cerebral organ (A-JV) changes of AA levels were compared with
      whole body systemic (A-PA) changes. Arterial total AA levels when compared with
      reported normal values are diminished by 46% in patients with isolated severe
      injuries. Cerebral outflow of glutamine is 6% of the total AA output compared
      with 73% in normals. The systemic outflow of glutamine in patients with brain
      injuries is 28% of total AA flow. Despite this high systemic output, significant
      hypoglutaminemia persists. Feeding for 3 days did not appreciably change the
      arterial plasma AA levels except that of glutamate and citrulline. A significant
      (p = 0.01) linear relationship between glutamine (product) and glutamate
      (precursor) was seen in JV samples but not in A or PA samples. The ratio of
      plasma glutamine to glutamate was decreased significantly only in JV during
      nutritional support, and this was caused mainly by an increase in glutamate
      levels. This may be owing to defective amidation to glutamine, inasmuch as gamma
      aminobutyric acid (GABA) levels were only minimally affected. Nutritional support
      improves the net release of glutamine from the brain. This suggests that
      supplementing the diet with glutamine may be beneficial to support systemic
      requirements in patients with severe head injuries.

PMID- 8858030
TI  - Nonoperative treatment of acute extradural hematomas: analysis of 80 cases.
AB  - Between 1986 and 1994, 270 patients with an acute extradural hematoma (EDH) were
      treated in the Department of Neurosurgery, Izmir State Hospital in Izmir, Turkey.
      Eighty patients with a supratentorial EDH of less than 30 mL in volume were
      treated conservatively. The 69 male and 11 female patients ranged in age from 5
      to 68 years. Five of the patients subsequently underwent surgery because of the
      deterioration in the level of consciousness and enlargement of EDH. One patient
      died after the operation. EDHs were localized in the temporal region in all five
      patients who subsequently required the surgical intervention. It has been
      emphasized that the findings on a computed tomographic (CT) scan performed very
      early may be misleading in patients with an EDH in progress. We concluded that
      the temporal location of EDHs with heterogeneous density in patients whose CT
      scan was performed less than 6 hours after trauma had a higher risk of hematoma
      growth and thus should be treated surgically. Periodic CT scans should be
      performed at brief intervals during the early phase of hospitalization.

PMID- 8858031
TI  - Biomechanical analysis of location of lag screw of a dynamic hip screw in
      treatment of unstable intertrochanteric fracture.
AB  - OBJECTIVE: The aim of this study was to assess the most adequate location of a
      lag screw of a dynamic hip screw in the treatment of an unstable
      intertrochanteric fracture. METHODS: Six pairs of proximal femora obtained from
      fresh adult cadavers were inflicted with iatrogenic unstable intertrochanteric
      fractures. Fractures of both sides were stabilized with two different favored
      locations of a lag screw and tested by a Material Testing System machine with
      increased loads to evaluate the relative migration of the femoral head. RESULTS:
      There was significant difference (p < 0.05) with less migration of the femoral
      head by inferior insertion of a lag screw in the frontal plane and central
      insertion in the coronal plane. CONCLUSIONS: Based on theoretical and
      experimental considerations, the most adequate location of a lag screw of a
      dynamic hip screw should be inferior in the frontal plane and central in the
      coronal plane.

PMID- 8858032
TI  - Comparison of nonbronchoscopic techniques with bronchoscopic brushing in the
      diagnosis of ventilator-associated pneumonia.
AB  - OBJECTIVE: To determine the diagnostic accuracy of quantitative cultures obtained
      via nonbronchoscopic protected specimen brushing (PSB) and nonbronchoscopic
      bronchoalveolar lavage (BAL) compared with quantitative cultures obtained by
      bronchoscopic PSB in surgical patients suspected of ventilator-associated
      pneumonia. DESIGN: Prospective, crossover controlled study of 15 ventilated
      surgical intensive care unit patients in a university teaching hospital. METHODS:
      Fifteen consecutive ventilated patients suspected of ventilator-associated
      pneumonia on the basis of leukocytosis, purulent sputum, and appearance of chest
      roentgenogram were enrolled. All patients underwent nonbronchoscopic PSB and BAL
      followed by bronchoscopic PSB. The duration of each procedure was noted. Culture
      results were considered positive only if greater than 10(4) colony forming units
      (CFU) per milliliter were present. MAIN RESULTS: Perfect concordance was noted
      between bronchoscopic PSB and nonbronchoscopic BAL (kappa = 1.0). The concordance
      between bronchoscopic PSB and nonbronchoscopic PSB was 93% ((kappa = 0.86). The
      nonbronchoscopic procedures were performed in significantly less time than the
      bronchoscopic procedure. CONCLUSION: Nonbronchoscopic PSB and BAL provide similar
      microbiologic data to bronchoscopic PSB in the diagnosis of ventilator-associated
      pneumonia while shortening procedure time significantly.

PMID- 8858033
TI  - Injury pattern and severity in lateral motor vehicle collisions: a Canadian
      experience.
AB  - OBJECTIVE: To determine the pattern and severity of injury and the outcome of
      front seat motor vehicle occupants after lateral impact crashes. DESIGN:
      Retrospective review undertaken in a Regional Trauma Unit (Sunnybrook Health
      Science Centre). MATERIALS AND METHODS: Review of seriously injured front seat
      motor vehicle occupants admitted to a Regional Trauma Unit over a 46-month period
      (September 15, 1989, to July 15, 1993) for whom vehicle crash information and
      occupant seat belt use were known. MEASUREMENTS AND MAIN RESULTS: Three hundred
      forty-eight front seat vehicle occupants were available for study; one hundred
      forty-one (41%) were involved in a lateral impact motor vehicle crash. Driver
      side lateral crashes (57%) were more common than passenger side impacts. Victims
      of lateral impact crashes had a significantly higher mean Injury Severity Score
      (25 compared with 20 for nonlateral crashes: p < 0.05), and the direction of
      impact was strongly associated with injury severity (p < 0.05). Lateral impact
      crashes resulted in substantially more significant chest (p < 0.01) and intra
      abdominal (p < 0.0001) injuries. Type of injury was significantly different
      between the lateral and nonlateral impact groups for facial, chest, abdominal,
      and musculoskeletal injuries. CONCLUSIONS: The direction of impact in motor
      vehicle crashes is strongly associated with the pattern and severity of organ
      injuries. Further attention to automobile safety design is necessary to better
      protect occupants involved in lateral impact crashes.

PMID- 8858034
TI  - Learning to not know: results of a program for ancillary cost reduction in
      surgical critical care.
AB  - OBJECTIVE: Compelling internal and external influences are stimulating global re
      evaluations of care standards for efficacy and cost. Critical care uses huge
      amounts of resources despite widespread shortages of beds and nurses. This study
      tested the hypothesis that ancillary expenditures can be decreased without
      compromising care. METHODS: Costs for laboratory tests, radiographs, blood
      products, nutritional supplements, and drugs were compared prospectively for all
      surgical intensive care unit care for two 4-month periods (January 1 to April 30,
      1994 and January 1 to April 30, 1995) at a urban university center. A systematic,
      multidisciplinary cost-reduction program began May 1, 1994, with emphasis on
      laboratory and radiographic testing and procedures, and blood product,
      nutritional, and drug therapies. Cohorts were compared by age, Acute Physiology
      and Chronic Health Evaluation (APACHE) II and III admission scores, and case mix.
      Outcome variables were hospital mortality, days in the intensive care unit and
      hospital, the development of multiple organ dysfunction syndrome, and
      expenditures. Cost data were taken weekly from the hospital's clinical
      information system. No new equipment was introduced during the study period
      except for pumps for patient-controlled analgesia, and there were no new critical
      pathways or other patient care guidelines. RESULTS: Case mix and all noncost
      variables were identical. Overall costs were reduced by 29% when normalized by
      the number of patient-days in each period. Laboratory testing was reduced in
      frequency by 24 to 32%, and cost by 26 to 28%. Comparable reductions in the cost
      of blood products (32%) were exceeded by the reductions in expenditures for
      nutritional supplements (49%) and pharmaceuticals (45%) (all, p < 0.01 or less).
      Modestly increased (2%) x-ray charges in 1995 were owing entirely to insertion of
      prophylactic inferior vena cava filters (each, $2,800, n = 5) and computed
      tomography scans for sinusitis (each, $350, n = 5), although the 7% reduction in
      portable chest radiographs that was achieved did not meet expectations.
      CONCLUSIONS: Substantial reductions in physician-ordered ancillary expenditures
      are possible without compromising the standard of care of critically ill
      patients, or the support of an elaborate framework of defined care plans. With
      additional experience, incremental savings may accrue from refinement of
      successful strategies and new approaches to intractable problems.

PMID- 8858035
TI  - Response after out-of-hospital cardiac arrest in the trauma patient should
      determine aeromedical transport to a trauma center.
AB  - OBJECTIVE: To evaluate whether aeromedical transport of trauma patients who
      sustain an out-of-hospital cardiac arrest (OHCA) is justified. DESIGN:
      Retrospective chart review. METHODS: We reviewed the outcome of 67 consecutive
      patients after OHCA with initial resuscitation who were transported to a Level I
      trauma center. Statistical analysis was used to develop a predictive model for
      survival. RESULTS: The overall survival was 19%. One of 28 patients with a second
      OHCA survived (p = 0.005). Logistic regression analysis demonstrated that the
      Revised Trauma Score at trauma center arrival (1.0 +/- 0.25, nonsurvivors vs.
      5.15 +/- 0.86, survivors, p = 0.0001), Injury Severity Score (34.9 +/- 2.9,
      nonsurvivors vs. 21.3 +/- 4.1, p = 0.037) and a sinus-based cardiac rhythm at the
      time of aeromedical team arrival were predictive of survival (R2 = 0.57, p =
      0.0001). Survivors were more likely to have been transported from an outside
      hospital (28% vs. 8% for scene runs), had a sinus rhythm on team arrival (42% vs.
      3%), and maintained a sinus rhythm on arrival at the trauma center (41% vs. 0%);
      however, these parameters were not predictive of survival in the statistical
      model. The neurologic outcome of the 13 survivors was good (preinjury state) in
      three cases, moderate disability (independent living) in three, severe disability
      (needing assistance) in five, and persistent vegetative state in two. Regression
      analysis was unable to differentiate survivors with a good neurologic recovery
      from the rest of the patient population. CONCLUSIONS: These results suggest that:
      (1) trauma patients who are resuscitated to a sinus rhythm after OHCA should be
      transported to a trauma center; (2) Revised Trauma Score and Injury Severity
      Score are useful to predict survival; and (3) neurologic outcome is not
      accurately predicted by this model.

PMID- 8858036
TI  - Defining "dead on arrival": impact on a level I trauma center.
AB  - OBJECTIVE: To determine the potential impact of defining criteria for "dead on
      arrival" (DOA) on a Level I trauma center. METHODS: From 1990 to 1994, trauma
      patients having cardiopulmonary resuscitation (CPR) performed by certified
      prehospital personnel were reviewed for time of CPR, outcome, and costs to
      determine whether any benefit would have been realized had DOA criteria been
      followed. RESULTS: A total of 106 patients had prehospital CPR; 20 did not meet
      DOA criteria and underwent resuscitation, three survived (15%). Eighty-six
      patients met DOA criteria; 16 were pronounced dead without further resuscitative
      efforts (in-hospital costs of $200/patient), while 70 (81%) had continued
      resuscitation with no survivors (in-hospital costs of $4150/patient). The
      positive predictive value for criteria was 100%. Had criteria been implemented,
      total cost savings over the 5-year period would have been $290,000. CONCLUSIONS:
      National DOA criteria could dramatically reduce the burden on trauma centers with
      an estimated minimum annual savings of $14 million.

PMID- 8858037
TI  - An evaluation of Ontario trauma outcomes and the development of regional norms
      for Trauma and Injury Severity Score (TRISS) analysis.
AB  - Outcomes analysis of patient care programs has become increasingly necessary for
      a variety of reasons in recent years. This has been particularly true for trauma
      programs. The Trauma and Injury Severity Score (TRISS) methodology was developed
      for this purpose in the context of the Major Trauma Outcome Study (MTOS). It
      provides an estimate of the probability of survival for individual patients,
      based on anatomic, physiologic, and etiologic factors. In addition, it allows
      hospitals and groups of hospitals to compare survival rates with other hospitals
      submitting data to the data base. However, the published coefficients for TRISS
      analysis have been derived from the MTOS data base. Patterns of practice, time to
      treatment, and other variables may be significantly different in other
      jurisdictions. To compare outcomes among similar hospitals within the province of
      Ontario, Canada, a regression analysis was performed to develop TRISS
      coefficients specific to the province. Data were obtained from the 12 trauma
      centers in the province treating the most severely injured patients (Injury
      Severity Score > 12). A total of 3,880 cases were eligible for TRISS analysis,
      over a 3-year period. Of these, 3,672 were patients with blunt trauma, and 208
      were victims of penetrating injury. Standard TRISS analysis of the patients with
      blunt trauma revealed z scores ranging from -10.260 to +1.849, with a mean of 
      6.648. Four centers had negative z scores that were significant (an absolute
      value of > 1.96 is considered statistically significant). Using Ontario TRISS
      coefficients, z scores ranged from -4.125 to +2.782, with a mean of 0.000. Four
      scores were significant with the Ontario coefficients, only one of which had been
      significant using the MTOS norms. The other three z scores were all positive,
      indicating more deaths than would have been predicted, but they were not
      significant when compared to the MTOS norms. The mean was also, of course, no
      longer significant. The area under the receiver operating characteristic curve
      analysis was strongly positive, and the Hosmer-Lemeshow Goodness-of-Fit analysis
      indicated good calibration. The new coefficients were subsequently validated by
      applying them to a subsequent year's data from patient records that did not form
      part of the original data set. This resulted in slightly improved z scores
      overall, and in most of the hospitals. This use of regional norms allows
      comparison with outcomes of patients cared for in hospitals within the same
      jurisdiction that are more similar to one another than to those in the MTOS, and
      helps to identify unexpected outcomes and outliers.

PMID- 8858038
TI  - Impact of a two-tiered trauma response in the emergency department: promoting
      efficient resource utilization.
AB  - OBJECTIVE: The purpose of this prospective study was to assess the impact of a
      two-tiered trauma response protocol on the expediency of identification,
      evaluation, and treatment of trauma patients in the Emergency Department.
      MATERIALS AND METHODS: At a Level I Trauma Center serving a suburban/urban
      population of approximately one million people, Emergency Department length of
      stay was tabulated for all consecutive Trauma Service admissions 6 months before
      and 6 months after implementation of a two-tiered trauma response protocol. This
      protocol, which uses specific triage criteria, consisted of the standard Surgery
      supervised trauma code response and an additional Emergency Medicine-supervised
      trauma alert response. RESULTS: Trauma Service admissions numbered 532 in the pre
      protocol period and 512 in the period after implementation of the protocol. In
      the first period, the Emergency Department length of stay was 289 minutes; in the
      second period, it was 241 minutes. Of the 512 patients in the post-protocol
      period, 183 were triaged to the new trauma alert group, reducing the number of
      Trauma Service consultations and decreasing Emergency Department length of stay
      by 139 minutes. The two levels of trauma response allowed accurate identification
      of the most seriously injured patients and improved the ability to predict those
      patients who would require direct disposition to the operating room or intensive
      care unit. CONCLUSIONS: Implementation of a two-tiered trauma response
      significantly decreased Emergency Department length of stay, allowed Emergency
      Medicine physicians to more rapidly identify, evaluate, and treat trauma patients
      requiring hospitalization, improved identification of patients requiring
      operating room or intensive care unit resources, and was time efficient and
      resource efficient.

PMID- 8858039
TI  - Trauma patients: an analysis of rural ambulance trip reports.
AB  - This study summarizes all 2,550 trauma-related rural ambulance trip reports filed
      for the period January 1 through December 31, 1991 from the 12 rural counties
      surrounding Augusta, Georgia. There were 13.1 trauma-related ambulance runs per
      1,000 population. Nearly one third of all rural ambulance runs are trauma
      related. Severe trauma constituted less than 8.0% of trauma cases. Forty-one
      cases died at the scene and 19 additional cases died from any cause within 30
      days of transport. The mean response time was 8.5 minutes and in 90% of all rural
      trauma runs the ambulance arrived in 17 minutes or less. Only 51.5% of runs had a
      rural hospital as a destination, 14.2% went directly to a trauma center, and
      nearly 20% to another urban hospital. Of the 71 severe trauma cases received by
      ambulance, rural hospitals transferred out only 13 cases, most of these to the
      regional trauma center. Of the 47 trauma cases transferred to the trauma center,
      33 were not severe.

PMID- 8858040
TI  - Direct injury to the cervical spine of a child by a lap-shoulder belt resulting
      in quadriplegia: case report.
AB  - Most pediatric cervical spine injuries from seat-belt restraints result from
      hyperflexion of the neck without direct injury to the spine from the restraining
      device. We report what we believe to be the first case of direct injury to the
      cervical spine by the shoulder component of a lap-shoulder seat belt. This
      resulted in quadriplegia. The mechanism of injury and recommendations to obviate
      such injuries are discussed.

PMID- 8858041
TI  - Multiple noncontiguous spine fractures at four levels in a neurologically intact
      patient.

PMID- 8858042
TI  - Arterial injury of the axilla: an unusual case after blunt trauma of the
      shoulder.
AB  - The lesion of an axillary artery after a shoulder dislocation without bone
      fractures is very rare. The most common lesion is the subtotal transection of the
      vessel. Vascular injuries may be associated with nervous lesions whose incidence
      ranges from 27 to 44%. The nervous lesions are highly invalidating. The symptoms
      which recur most frequently are motor and sensitive deficiencies and a distal
      ischemia which, in some cases, may not be noted owing to the extensive collateral
      network. Whenever these symptoms are covered or absent, as in this case report,
      an angiography of the upper limb becomes essential for correct diagnosis and
      treatment.

PMID- 8858043
TI  - Open knee dislocation associated with vascular injury successfully salvaged by
      primary arthrodesis in an elderly patient: a case report.
AB  - Treatment by primary arthrodesis of the knee joint after temporary intraluminal
      shunt placement in a 70-year-old man with open knee dislocation involving the
      popliteal vessels is reported. After temporary shunting, the definitive vascular
      reconstruction of both the popliteal artery and vein was established by end-to
      end anastomoses because of the shortening effect of the arthrodesis. Two skin
      coverage procedures were performed on day 0 and day 18. The patient recovered
      activity to a level near his pretrauma status. Primary arthrodesis for open knee
      dislocation associated with vascular injury in an elderly patient may be an
      efficacious procedure, depending on the patient's age, occupation, and level of
      activity.

PMID- 8858044
TI  - Carotid injury: postrevascularization hemorrhagic infarction.

PMID- 8858045
TI  - Angiographic embolization of a penetrating traumatic renal arteriovenous fistula.

PMID- 8858046
TI  - Advances in ALS.

PMID- 8858047
TI  - Excitotoxicity hypothesis.

PMID- 8858048
TI  - Molecular genetic basis of familial ALS.
AB  - Familial amytrophic lateral sclerosis (FALS) is transmitted in a mendelian
      fashion as an autosomal dominant (DFALS) or an autosomal recessive (RFALS) trait.
      Both DFALS and RFALS are genetically heterogeneous. Fifteen percent of DFALS
      families have mutations in the gene for Cu, Zn superoxide dismutase (SOD1) which
      is coded on chromosome 21. The locus for one form of RFALS maps to chromosome
      2q33. Forty-six mutations in the SOD1 gene have been reported in DFALS families.
      These mutations result in decreased SOD1 activity and shortened half-life of the
      protein in most instances. Transgenic mice overexpressing mutated SOD1 protein
      develop an ALS-like disease which suggests that the degeneration of motor neurons
      in DFALS is caused by the gain of a novel toxic function by mutated SOD1 rather
      than by the decrease of SOD1 activity. Several possible mechanisms of the novel
      neurotoxic function of mutated SOD1 are discussed.

PMID- 8858049
TI  - Cell death mechanisms in ALS.
AB  - Mutations in copper-zinc superoxide dismutase (CuZnSOD) that are associated with
      familial ALS (FALS) are dominant, gain-of-function mutations, but the nature of
      the function gained has not been identified. In addition to catalyzing the
      dismutation of superoxide, copper-zinc superoxide dismutase also displays
      peroxidase activity. Whereas mutants A4V and G93A retained superoxide dismutase
      activity, they demonstrated a markedly enhanced copper-dependent peroxidase
      activity in comparison with that of the wild type enzyme as detected by the spin
      trap 5,5'-dimethyl-1-pyrroline N-oxide (DMPO) in electron paramagnetic resonance
      measurements. Two copper chelators, diethyldithiocarbamate and penicillamine,
      inhibited the mutants' peroxidase activity, but not that of the wild type enzyme,
      at stoichiometric concentrations; furthermore, these copper chelators enhanced
      neural survival in a cell-culture model of ALS but did not alter survival of
      cells expressing only wild type copper-zinc superoxide dismutase. These
      observations suggest that oxidative reactions catalyzed by mutant copper-zinc
      superoxide dismutases may initiate the neuropathologic changes of FALS.

PMID- 8858050
TI  - Autoimmunity and ALS.
AB  - Significant evidence has accrued suggesting that antibodies to voltage-gated
      calcium channel are observed in at least some patients with sporadic ALS (SALS)
      and that such antibodies alter the function of these ion channels in vitro and in
      vivo. Further, passive transfer of these immunoglobulin-containing fractions into
      mice produces changes at the neuromuscular junction that are very similar to
      changes observed in patients with SALS. These changes reflect local alterations
      in intracellular Ca2+ homeostasis and, in animal models, may also evidence early
      changes of motoneuron injury, such as Golgi apparatus swelling and fragmentation.
      Although not yet documented to induce motoneuron death in vivo, SALS
      immunoglobulins induce Ca(2+)-dependent apoptosis in a differentiated motoneuron
      hybrid cell line via a mechanism that involves oxidative injury. SALS
      immunoglobulin-mediated apoptosis in these cells is regulated by the presence of
      the same calcium-binding proteins that may modulate selective motoneuron
      vulnerability in SALS.

PMID- 8858051
TI  - Motor neuron growth factors.

PMID- 8858052
TI  - Mechanisms of selective motor neuron death in transgenic mouse models of motor
      neuron disease.
AB  - To examine the mechanism(s) of disease underlying ALS, transgenic mouse models
      have been constructed that express aberrant neurofilaments or mutations in the
      abundant, cytoplasmic enzyme superoxide dismutase 1 (SOD1). In addition to
      progressive weakness arising from selective motor neuron death, mice expressing a
      modest level of a point mutant in neurofilament subunit NF-L show most of the
      pathologic hallmarks observed in familial and sporadic ALS, including perikaryal
      proximal axonal swellings, axonal degeneration, and severe skeletal muscle
      atrophy. Additional mice expressing familial ALS-linked mutations in the
      cytoplasmic enzyme SOD1, the only proven cause of ALS and which accounts for
      approximately 20% of familial disease, have demonstrated that at least one
      mutation causes disease through acquisition of an adverse property by the mutant
      enzyme, rather than elevation or loss of SOD1 activity. These animals not only
      provide a detailed look at the pathogenic progression of disease, but also
      represent a tool for testing hypotheses concerning the specific mechanism(s) of
      neuronal death and for testing therapeutic strategies.

PMID- 8858053
TI  - Neuropathology of ALS: an overview.

PMID- 8858054
TI  - Diagnostic criteria in clinical trials.

PMID- 8858055
TI  - Natural history of ALS: symptoms, strength, pulmonary function, and disability.

PMID- 8858056
TI  - Development of measurement techniques.

PMID- 8858057
TI  - Clinical trials of riluzole in patients with ALS. ALS/Riluzole Study Group-II.
AB  - Two double-blinded, placebo-controlled clinical trials of riluzole have now been
      carried out in more than 1,100 patients with ALS. The results of both studies
      show a modest benefit in prolonging survival that is statistically significant.
      These results led to the availability of this drug by the Food and Drug
      Administration for use in the United States beginning in early 1996. This is the
      first drug that has been available for ALS. It begins a new era in both basic and
      clinical research in an attempt to find a cure for this disease.

PMID- 8858058
TI  - Recombinant human insulin-like growth factor-I in ALS: description of a double
      blind, placebo-controlled study. North American ALS/IGF-I Study Group.

PMID- 8858059
TI  - Issues in clinical trial design I: Use of natural history controls. A protagonist
      view.

PMID- 8858060
TI  - Issues in clinical trial design I: Use of natural history controls. An antagonist
      view.

PMID- 8858061
TI  - Issues in clinical trial design. II: Selection of end point measures.

PMID- 8858062
TI  - Drug combination treatment in patients with ALS: current status and future
      directions.

PMID- 8858063
TI  - Advances in ALS workshop summary: Research and future goals.

PMID- 8858064
TI  - ALS care: a resource for measuring and improving ALS outcomes.
AB  - The Amyotrophic Lateral Sclerosis Clinical Assessment, Research, and Education
      Project (ALS CARE) will conduct outcomes research and develop educational
      programs that benefit ALS patients and neurologists. An advisory board of
      neurologists, who are experts in ALS, will establish the policies governing this
      project and control the dissemination of aggregate data on ALS practices and
      outcomes. As a first step toward improving the care of ALS patients, a data
      coordinating center has been established in the Center for Outcomes Research at
      the University of Massachusetts Medical Center, which will manage a North
      American Database of ALS Outcomes. This voluntary database is designed to (1)
      guide the development of educational programs to improve the care of ALS patients
      and (2) provide a mechanism for neurologists to evaluate the impact of their
      diagnostic and therapeutic decisions in a manner that is timely, confidential,
      and objective.

PMID- 8858065
TI  - The impact of the approval of riluzole.

PMID- 8858066
TI  - Management of ALS: nutritional care.

PMID- 8858067
TI  - Improving education for physicians and for patients.

PMID- 8858068
TI  - Management of ALS: respiratory care.

PMID- 8858069
TI  - The economic impact of ALS.
AB  - ALS is a progressive degenerative neuromuscular disease for which there is no
      known cause, treatment, or cure. The steady disease progression of muscle
      weakness eventually causes paralysis, disabling the patient. Day-to-day patient
      care and management most frequently fall to family members. The resultant
      financial burden can be enormous. We review financial issues related to the
      diagnosis, management of disease progression, and issues of life support. Cost
      effective solutions are discussed. It is believed the key to reduction of costs
      is education of the health care community, patients and families, and third-party
      payers.

PMID- 8858070
TI  - Management of common pediatric fractures.
AB  - Pediatric fractures are seen commonly in emergency departments. Pediatricians are
      usually the first physicians to assess injured children. Pediatricians should be
      comfortable in evaluating the fracture and interpreting radiographs prior to
      consulting an orthopedist. An understanding of the differences between pediatric
      and adult bone makes the assessment of children and their radiographs easier.
      Musculoskeletal injuries, fractures, and sprains are common, most of which
      require minimal care. Growth plate injuries, however, pose a risk for permanent
      deformity and must be managed with care.

PMID- 8858071
TI  - Pediatric and adolescent sports medicine.
AB  - The majority of pediatric sports-related injuries are relatively benign and are
      easily treated with conservative measures. When surgical intervention is
      required, it is usually effective in returning the athlete to participation
      within a reasonable time frame. Effective care of pediatric athletes, however,
      involves not only knowledge of the many types of injuries and their treatments
      but also insight into the demands of the various sports and the needs of
      individual athletes. Treatment and resumption of participation recommendations
      frequently vary depending on the patient's sport, level of participation, and
      willingness to substitute alternative sports for his or her primary one. As
      always, individualizing treatment leads to greater patient satisfaction and
      improved results.

PMID- 8858072
TI  - Orthopedic aspects of child abuse.
AB  - Fractures are one of the most common manifestations of child abuse. Pediatricians
      and other physicians caring for children must have a clear understanding of the
      injury patterns sustained by children in abusive situations and be able to
      recognize those injuries. A thorough history and physical examination and
      accurate radiographic interpretation are essential. Early identification of
      nonaccidental trauma is imperative because proper intervention has been shown to
      be effective.

PMID- 8858073
TI  - Three common causes of childhood hip pain.
AB  - Disorders of the hip that result in pain during childhood are not random and
      chaotic events. The work of numerous investigators demonstrates that each
      condition has distinguishing characteristics. These characteristics are found in
      the manner of presentation, the physical examination, and the diagnostic study.
      Familiarity, with these conditions, attention to the details of the patients'
      history, and a careful eye for the details of physical examination allow skillful
      physicians to devise a plan of investigation that results in a successful
      diagnosis.

PMID- 8858074
TI  - Pediatric knee. Clinical assessment and common disorders.
AB  - Knee pain and injury are commonly seen in children and adolescents. A
      comprehensive evaluation of the knee is built on an appreciation of the anatomy,
      biomechanics, and pathophysiology of common disorders. This article considers
      these issues and describes a sequential technique for physical examination of the
      knee. Relevant imaging options and management strategies also are discussed.

PMID- 8858075
TI  - Evaluation and management of pediatric foot deformities.
AB  - There are myriad diagnoses that can occur in children's feet, and this article
      presents only a handful. Systematic evaluation beginning with a detailed history
      and careful physical examination, together with a knowledge of the natural
      history of these conditions, allows the primary care physician to be a much
      needed resource for the family and provide cost-effective, efficient care while
      referring patients that need pediatric orthopedic intervention.

PMID- 8858076
TI  - Congenital disorders of the hand and upper extremity.
AB  - This article summarizes normal formation and growth of the upper limb as a basis
      for understanding malformation. Shoulder anomalies, including Sprengel's
      undescended scapula, clavicle pseudarthrosis, cleidocraniodystostosis, and
      Poland's syndrome, are presented. Classification and examples of limb
      malformations are discussed as well as neuromuscular disorders, such as obstetric
      brachial plexopathy, cerebral palsy, and arthrogryposis. The author hopes that
      this article provides a basic understanding of the evaluation necessary for
      appropriate counseling and referrals for treatment of the child with hand and
      upper extremity congenital deformities.

PMID- 8858077
TI  - The musculoskeletal management of children with cerebral palsy.
AB  - Orthopedic management of children with cerebral palsy is best accomplished with a
      team approach, which generally is effective in the other neuromotor disabilities
      of childhood, such as myelomeningocele and muscle disease. Because contracture
      development is inevitable in growing children with spastic musculature or muscle
      imbalance and is a prime cause of musculoskeletal dysfunction, its control over
      time using therapy, bracing, and medication is essential. Problems such as severe
      contracture, joint deformity, and scoliosis interfere with the basic requirement
      of comfortable seating in children with quadriplegic involvement and frequently
      require surgery. In ambulatory children, the use of three-dimensional gait
      analysis has allowed multilevel surgery to be appropriately planned, minimizing
      exposure to surgery and therapy.

PMID- 8858078
TI  - Spina bifida.
AB  - Spina bifida (myelomeningocele) is the most common major birth defect among live
      born infants. It is now recognized that half of those cases are preventable if
      folate is given periconceptionally. Epidemiology is discussed, together with an
      overview of approaches to orthopedic problems from birth to maturity.

PMID- 8858079
TI  - Mentoring: leaving a legacy of opportunity and responsibility.

PMID- 8858080
TI  - Top 10 easy eats. A physician's bread and butter.

PMID- 8858081
TI  - Drug therapy for chronic urticaria.

PMID- 8858082
TI  - Hypertension in women and the elderly. Some puzzling and some expected findings
      of treatment studies.
AB  - Almost 65% of the US population over age 60 has hypertension (systolic blood
      pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg), which is
      strongly related to increased rates of coronary artery disease (CAD), stroke, and
      death. The need for treatment seems obvious. However, in young and middle-aged
      women, treatment is not straightforward, and trials have not specifically
      targeted this group. Data extrapolated from existing studies suggest that
      treatment of hypertension does not confer the same protection against CAD and
      stroke in women as it does in men. In fact, a trend toward harm in young and
      middle-aged white women receiving stepped care for hypertension has been
      reported. Therefore, for now, treatment of women in this age-group should be
      conservative; drugs should be prescribed only after a focused trial of lifestyle
      modification has failed. Until recently, elderly subjects were also excluded from
      treatment studies, despite the fact that they are at high risk for morbidity and
      death from hypertension-related diseases. Recent studies have established that
      treatment of hypertension in the elderly is extremely effective, that elderly
      women should be treated as aggressively as elderly men, and that low-dose
      diuretic or beta-blocker therapy should be initiated if lifestyle modifications
      are not effective.

PMID- 8858083
TI  - Lifestyle modifications for hypertension. The many benefits are worth the effort.
AB  - Any approach to antihypertensive therapy should include lifestyle modifications.
      In the beginning, emphasis should be on weight loss and exercise, along with
      moderation of alcohol use and cessation of smoking. Patients should be encouraged
      to consume fresh rather than processed (and thus high-salt) foods and to limit
      use of salt in cooking and at the table. Even if patients eventually require
      antihypertensive medications, lifestyle modifications should continue, since
      there is evidence that such measures minimize the number and dose of medications
      required.

PMID- 8858084
TI  - Options in antihypertensive drug therapy. Help in choosing from among the many
      agents.
AB  - The fifth report of the Joint National Committee on Detection, Evaluation, and
      Treatment of High Blood Pressure (JNC V) states that "because diuretics and beta
      blockers are the only classes of drugs that have been used in long-term
      controlled trials and shown to reduce morbidity and mortality, they are
      recommended as first choice agents unless they are contraindicated or
      unacceptable." These guidelines are important, but practitioners should remember
      that many effective and well-tolerated classes of drugs are available for
      treating hypertension, and one may have greater usefulness than another in a
      given patient. For example, an angiotensin-converting enzyme inhibitor may be
      appropriate in a patient with hypertension and congestive heart failure or
      diabetic nephropathy. A calcium channel blocker may be beneficial in a patient
      with hypertension and concomitant angina. Results of prospective studies
      comparing classes of antihypertensive drugs and measuring clinically significant
      end points may help guide pharmacotherapy in the future.

PMID- 8858085
TI  - Resistant hypertension. Suggestions for dealing with the problem.
AB  - With appropriate evaluation of both patient- and physician-related factors, many
      cases of resistant hypertension can be resolved. Patients often do not understand
      the implications of their disease and need specific information regarding the
      importance of compliance with medication schedules and dietary restrictions.
      Physicians should also consider the possibility of drug resistance or the
      presence of an identifiable secondary cause, such as renal artery stenosis,
      chronic renal parenchymal disease, or pheochromocytoma.

PMID- 8858086
TI  - New and improved vaccines. Promising weapons against varicella, hepatitis A, and
      typhoid fever.
AB  - The initial motives behind development of vaccines were to protect against life
      threatening infections (eg, rabies, diphtheria), to eradicate sweeping outbreaks
      of serious diseases (eg, paralytic poliomyelitis, smallpox), and to prevent
      diseases in a vulnerable population by the immunization of surrogates (eg,
      rubella immunization to prevent congenital rubella syndrome). Now a fourth motive
      emerges: prevention of less serious infections to improve quality of life. The
      advantages of new vaccines and immunization programs should no longer be measured
      exclusively in terms of the number of lives saved but should take into account
      direct and indirect cost savings and overall benefit to individual and societal
      health and well-being. Although varicella and hepatitis A infections can be life
      threatening, most cases are self-limited and have no significant sequelae.
      Immunization is more likely to improve quality of life than to save lives.
      Vaccination against typhoid remains a potentially lifesaving act in developing
      nations, but even the newer typhoid vaccines were developed primarily to reduce
      the frequency and severity of adverse reactions to immunization rather than to
      improve the protective efficacy of the original heat-phenol inactivated vaccine.
      Varicella virus vaccine, hepatitis A virus vaccines, and the typhoid
      polysaccharide Vi capsular vaccine represent important additions to immunization
      agents. These vaccines are immunogenic, clinically effective, and generally safe,
      with infrequent and usually mild adverse reactions. Their favorable benefit-risk
      ratio should encourage their appropriate use. The Centers for Disease Control and
      Prevention, the American Academy of Pediatrics, and the American Academy of
      Family Physicians have already recommended varicella vaccine for universal
      immunization of children. Formal recommendations that hepatitis A vaccine also be
      routinely used for all children may be forthcoming in the next few years; in the
      meantime, persons at high risk should be immunized. Typhoid vaccination will
      likely continue to be used selectively for those who have significant contact
      with the organism or those who travel to typhoid-endemic countries.

PMID- 8858087
TI  - Urinary calculi during pregnancy. When are they cause for concern?
AB  - Urolithiasis during pregnancy, though rare, can be challenging both
      diagnostically and therapeutically. It is helpful if the physician is quick to
      suspect the presence of stones in the presence of appropriate signs and symptoms,
      particularly flank pain and tenderness, hematuria, or unresolved bacteriuria.
      Ultrasonography is the diagnostic imaging method of choice, but modified
      intravenous urography should be performed whenever this study is necessary for a
      prompt diagnosis. In the absence of sepsis, renal failure, or intractable pain,
      conservative management with hydration, analgesics, and (if infection is present)
      antibiotics is the favored initial approach. If conservative management fails,
      stent insertion or placement of a percutaneous nephrostomy tube may be
      appropriate. Ureteroscopy with stone manipulation for distal ureteral stones
      during pregnancy has also been reported in some cases. If these methods fail,
      open surgery should be used for stone removal.

PMID- 8858088
TI  - Depression in late life. Diagnosis, course, and consequences.
AB  - Both major depression and dysthymia are common disorders in late life. However,
      making an accurate diagnosis may be more challenging than diagnosing depression
      in younger persons both because of comorbid general medical conditions and
      because of the illnesses, cognitive disturbances, and myriad adverse life
      experiences the elderly face. Often, dysphoria is sloughed off as an
      understandable response to adversity, and the diagnosis of depression is missed.
      Thus, elderly persons with major depression and dysthymia may be exposed to
      unnecessary prolonged suffering and to the disruptions of family life, impairment
      of functioning, worsening of comorbid general medical illness, and premature
      death that are the hallmarks of untreated depression.

PMID- 8858089
TI  - Depression in late life. Special considerations in treatment.
AB  - In late life, depression and dysthymia are prevalent, serious, but treatable
      disorders. Unfortunately, treatment often is delayed or withheld because of
      difficulties in recognizing and diagnosing the condition. Treatment may also be
      withheld when the depression is incorrectly perceived as hopeless or its
      treatment as futile. Optimal treatment includes educating the patient and family
      about depression and its treatment, selecting the appropriate antidepressant
      regimen, and providing psychosocial intervention to instill hope, improve
      compliance, and minimize disability. Treatment must be geared toward not only
      helping patients get well but helping them keep well.

PMID- 8858090
TI  - Urologic emergencies. Conditions affecting the kidney, ureter, bladder, prostate,
      and urethra.
AB  - Prompt, thorough evaluation is needed when patients present with symptoms of
      renal colic, acute urinary retention, prostatitis, pyelonephritis, and other
      urologic emergencies. Primary care physicians have an important role in initial
      workup and treatment. Once the diagnosis is determined, urologic consultation may
      be necessary for definitive treatment.

PMID- 8858091
TI  - Urologic emergencies. Trauma injuries and conditions affecting the penis,
      scrotum, and testicles.
AB  - Urologic emergencies involving the penis, scrotum, and testicles include
      priapism, paraphimosis, testicular torsion, and Fournier's gangrene. Familiarity
      with the signs and symptoms of these conditions can lead to prompt diagnosis.
      Special care is needed in differentiating testicular torsion from the more common
      condition of epididymitis. Evaluation of trauma injuries of the genito-urinary
      tract includes classification (blunt or penetrating), assessment of the extent of
      injury, and urologic consultation if appropriate.

PMID- 8858092
TI  - Tuberculosis. Recommendations for screening, prevention, and treatment.
AB  - The incidence of tuberculosis has been increasing in recent years. Therefore,
      routine screening with the Mantoux test is important in persons at high risk of
      infection or progression to active disease. Test results are interpreted on the
      basis of each patient's risk factors. Persons at high risk may benefit from
      preventive therapy. Active tuberculosis is treated with multidrug regimens to
      avoid the development of bacterial resistance. Healthcare workers at risk for
      occupational exposure should undergo routine screening. Required notification of
      the public health department ensures that patients receive appropriate treatment
      and that proper investigation is done to prevent further spread of the disease.

PMID- 8858093
TI  - Alcoholism in women. More common--and serious--than you might think.
AB  - Rising rates of alcohol use disorders and disproportionate medical complications
      in alcoholic women, plus the dire consequences to their fetuses and children,
      suggest the need for increased attention to this problem in medical practice.
      Direct, systematic inquiry about drinking patterns is the most practical and
      efficient way to detect cases of alcoholism. The potential dangers of prescribing
      abusable psychoactive drugs for alcoholic women, because of their greater demand
      or apparent need for these agents, should dictate attention to alcohol use in all
      medical practice settings.

PMID- 8858094
TI  - Stress-activated protein kinase activation is the earliest direct correlate to
      the induction of secretagogue-induced pancreatitis in rats.
AB  - We compared the cellular events induced by hyperstimulation of rats with
      caerulein which induces acute pancreatitis, to bombesin, which does not induce
      pancreatitis. Both secretogogues induced the intracellular activation of
      trypsinogen and the colocalization of lysosomal hydrolases and zymogen granules
      within 10-15 minutes. These data indicate that these parameters, previously
      thought to be crucial initiating events of pancreatitis, are not definitive
      cellular markers of the disease. We then compared the abilities of the two
      secretagogues to activate stress-activated protein kinase (SAPK). Significant
      effects of caerulein hyperstimulation on SAPK activity were observed within 5
      minutes, the maximum (57-fold) activation was evident after 15 minutes, and
      levels remained above control for at least 3 hours. In comparison,
      hyperstimulation with bombesin induced a maximal 5-fold increase of SAPK activity
      which returned to basal within one hour. These data indicate that SAPK activity
      is the earliest and best correlated cellular marker associated with secretagogue
      induced pancreatitis.

PMID- 8858096
TI  - Direct inhibitory effects of an antisense oligodeoxynucleotide upon the volume
      sensitive chloride current in rat osteoblast-like (ROS 17/2.8) cells.
AB  - The effects of a 15-mer antisense c-myc phosphorothioate modified
      oligodeoxynucleotide (OdN) upon the volume-sensitive Cl- current in ROS 17/2.8
      cells were investigated using the whole-cell configuration of the patch clamp
      technique. At 5 microM, the OdN reversibly inhibited the current in a voltage-
      and time-dependent fashion. This was evident from the reduction in the peak
      current as assessed at the termination of each voltage pulse and an acceleration
      of the time-dependent inactivation present at strongly depolarised potentials.
      The kinetic modifications induced by the OdN suggest it may act by blocking the
      pore of open channels when the cell membrane potential is depolarised.

PMID- 8858095
TI  - Novel difference in IF1 reactivity to Zn2+ in rabbit versus rat cardiomyocytes,
      mitochondria, and submitochondrial particles.
AB  - Zn2+ has a paradoxical effect on IF1-ATPase interaction in cardiac muscle
      mitochondria in so-called slow heart-rate mammalian species like rabbit. In such
      slow heart-rate mammalian species, it completely prevents IF1-mediated ATPase
      inhibition regardless of pH while concomitantly causing full IF1 binding to the
      ATPase, again, regardless of pH (Rouslin et al. (1993) J. Bioenerget. Biomembr.
      25, 297-306). While our earlier study suggested that there are two kinds of IF1
      ATPase interaction, a docking interaction and an ATPase inhibitory interaction
      with Zn2+ promoting docking and interfering with inhibition, it did not yield
      information on whether Zn2+ interacted primarily with IF1, with the ATPase, or
      with both. In the present study we show that, in contrast to its effects in
      rabbit cardiomyocytes, mitochondria, and SMP in which Zn2+ fully blocked IF1
      mediated ATPase inhibition, Zn2+ actually enhanced ATPase inhibition in rat
      cardiomyocytes, although the extent of this effect was limited by the low level
      of IF1 in rat cardiomyocytes. Moreover, Zn2+ had no effect on IF1-mediated ATPase
      inhibition in rat heart mitochondria and, as suggested by inter and intra-species
      IF1 binding to SMP, the different effects of Zn2+ in rabbit versus those in rat
      appear to be mediated primarily through the different reactivities of rabbit and
      rat IF1 to Zn2+.

PMID- 8858097
TI  - Inhibition of Raf/MAPK signaling in Xenopus oocyte extracts by Raf-1-specific
      peptides.
AB  - Raf-1 is an upstream element of the mitogen-activated protein kinase (MAPK)
      pathway which leads to cell proliferation and differentiation. In this study Raf
      1 derived peptides comprising the conserved amino acid residues Arg89 and Ser259,
      involved in binding of activated Ras and 14-3-3 proteins, respectively, were
      shown to interfere with MAPK activation in extracts from immature Xenopus
      oocytes. Lipids prepared from oocyte extracts can stimulate MAPK in a Ras- and
      protein kinase C-independent manner. This lipid-induced MAPK activation is
      blocked by a Raf-1 derived peptide comprising Ser259.

PMID- 8858098
TI  - Insulin-induced in situ phosphorylation of the insulin receptor located in the
      plasma membrane versus endosomes.
AB  - The binding of insulin to the plasma membrane insulin receptor initiates two
      dynamic processes: (i) autophosphorylation of the receptor on tyrosine residues,
      activating the intrinsic tyrosine kinase activity required for insulin signaling,
      and (ii) endocytosis of the receptor. Recent evidence (Kublaoui et al., J. Biol.
      Chem. 270, 59-65, 1995) demonstrates that in stimulated adipocytes, the
      internalized insulin receptor is not only more highly phosphorylated than the
      receptor remaining on the plasma membrane of the cell, but that IRS-1 binding and
      phosphorylation also occur in the endosomes. These data suggest that the
      intracellular insulin receptor mediates insulin action. Utilizing 3T3-L1
      adipocytes, we substantiate and extend these findings to document the
      distribution of receptor between the plasma membrane and the endosomal
      compartment of insulin-stimulated cells and map the extent and location of the
      tyrosine phosphorylation sites on the receptor residing in these two cellular
      locations. We find that following insulin stimulation (i) 90% of the receptor
      associated phosphate is located in the endosomal compartment, (ii) the endosomal
      receptor is most highly phosphorylated in the tyrosine kinase domain, and (iii)
      significant levels of juxtamembrane domain phosphorylation are detected in the
      endosomal receptor. These data support the role of the endosomal insulin receptor
      as the major transducer of insulin action.

PMID- 8858099
TI  - Eotaxin stimulates eosinophil adhesion to human lung microvascular endothelial
      cells.
AB  - Effects of the human C-C chemokines eotaxin, MIP-1 alpha, and RANTES on human
      eosinophil or neutrophil adhesion to human lung microvascular endothelial cells
      (LMVEC) were investigated. Basal adhesion of unstimulated eosinophils to LMVEC
      was increased following pretreatment of LMVEC with TNF alpha (10ng/ml) for 6h.
      Stimulation of eosinophils with eotaxin (30 and 100ng/ml) resulted in increased
      adhesion to LMVEC pretreated with TNF alpha but not culture medium. Neutrophil
      adhesion was not increased by eotaxin under similar conditions. Neither MIP-1
      alpha (3-100 ng/ml) nor RANTES (3-100 ng/ml) increased eosinophil or neutrophil
      adhesion to LMVEC pretreated for 6 h with either TNF alpha (10 ng/ml) or culture
      medium. Monoclonal antibodies (mAb) against eosinophil adhesion molecule VLA-4
      (2B4; 30 micrograms/ml) but not CD18 (6.5E; 10 micrograms/ml) inhibited eotaxin
      induced eosinophil adhesion to TNF alpha-activated LMVEC. 2B4 in combination with
      6.5E reduced adhesion to basal levels. These data show that eotaxin, but not MIP
      1 alpha or RANTES, stimulates eosinophil adhesion to LMVEC and that this effect
      can be abolished by anti-VLA-4 and CD18 mAb in combination. These results suggest
      that eotaxin may facilitate eosinophil migration from blood vessels in the lung
      by increasing eosinophil adhesion to endothelial cells.

PMID- 8858100
TI  - Kinetic analysis and comparison of models of xylose metabolism by Klebsiella
      planticola.
AB  - A model for the degradation of xylose and ethanol production by Klebsiella
      planticola is proposed and compared with the exponential and Michaelis-Menten
      approaches. This model is based on the energy system diagrams and it is a
      simplified version of a previous model developed for the glucose and ethanol
      kinetics of the yeast Saccharomices cerevisiae. In this model the dynamics of the
      substrate and of the final product are strictly related by means of the cellular
      activity. This model shows superior performances with respect to the two
      alternatives, behaving better along the whole dynamics.

PMID- 8858101
TI  - Retinoic acid induces cell proliferation and modulates gelatinases activity in
      human osteoclast-like cell lines.
AB  - The effect of Retinoic Acid (RA) on human osteoclast-like cell lines, obtained
      from Giant Cell tumors (GCT) of bone, has been investigated evaluating its action
      on bone resorption, cell proliferation, microtubular organization and gelatinases
      expression and activity. Increasing concentrations of RA significantly dose
      dependently decreased GCTs bone resorption, while 10(-7) M RA promoted an
      increase of cell proliferation. By immunofluorescence we demonstrated that GCTs
      express A and B gelatinases and, by zymography, that their activity was enhanced
      in medium collected from GCTs cultured in the presence of 10(-7) M RA. These data
      indicate that RA increases cell proliferation and modulates metalloproteinases
      (MMPs) activity, crucial events during the migration of osteoclast precursors
      toward bone surfaces.

PMID- 8858102
TI  - Modeling interpretation of microbe metabolism detected by nuclear magnetic
      resonance.
AB  - A new modeling approach is discussed for the analysis of microbial dynamics. It
      is based on structurally nonlinear compartmental models and on the dynamics of
      the substrate and product. Experimental data were acquired by NMR spectroscopy
      which is a noninvasive technique. This combined approach was tested with the
      fermentation of glucose to ethanol by Saccharomyces cerevisiae. The model was
      fitted with the experimental data to obtain the values of the parameters of the
      model. Similar processes can be analyzed and compared using this approach.

PMID- 8858103
TI  - Protein engineering of venom toxins by synthetic approach and NMR dynamic
      simulation: status of basic amino acid residues in waglerin I.
AB  - The tertiary structure of waglerin I has been determined by NMR and dynamic
      simulated annealing [Chuang et al., Biochim. Biophys. Acta 1292, 145-155 (1996)].
      It is believed that the peptide basicity of waglerin may play an important role
      for its activity due to its high content of basic amino acids. In order to
      investigate the active site of the toxin, seven analogues of waglerin, [Ala3]
      waglerin, [Ala7]-waglerin, [Ala10]-waglerin, [Ala14]-waglerin, [Ala18]-waglerin,
      [Ala20]-waglerin and [Ala22]-waglerin have been synthesized chemically by single
      replacement of basic amino acid residues one by one with Ala. By correlation of
      structures for each analogue with LD50 toxicity bioassays, it is found that the
      [Ala10]-waglerin exhibits no toxicity and the active site of the native toxin
      seems to reside in the proximity of the disulfide loop, which is spatially close
      to His10. Furthermore, the closer is the disulfide loop to the basic amino acid
      in waglerin, the more influential is the basic amino acid on the toxicity of
      waglerin. Based on the tertiary structure of waglerin, the structures of all
      synthetic analogues were derived based on computer-simulated modelling. By the
      pair-wise structural comparison, the disulfide loop in [Ala10]-waglerin analogue
      is found to be twisted as compared to the native form, in agreement with the lack
      of toxicity for this synthetic analogue.

PMID- 8858104
TI  - Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma
      cells.
AB  - Gap junction-mediated communication is required for normal cellular growth and
      differentiation. As cancer is thought to be a manifestation of the breakdown of
      cell-cell communication, with the concomitant loss of growth control, it would be
      expected that alterations in the primary structure, processing, oligomerization
      or trafficking of connexin (cxn) molecules would have a profound effect on the
      neoplastic process. Here we a present a preliminary immunohistochemical and
      molecular analysis of cxn 43 expression in prostatic epithelial cells from
      resected human tissue. Our data indicate that benign prostatic epithelial cells
      express cxn 43 protein, but that this expression is diminished in more advanced,
      anaplastic cancer cells. These data suggest that decreased connexin expression is
      not involved in the initiation of prostate cancer, but rather occurs during the
      progression of the disease.

PMID- 8858105
TI  - The mouse genes for the EP1 prostanoid receptor and the PKN protein kinase
      overlap.
AB  - PKN is a newly discovered protein kinase that has been shown to mediate GTPase
      Rho dependent intracellular signalling. We show in this report that the mouse PKN
      gene is situated at the mouse EP1 prostanoid receptor gene locus and that the two
      genes are overlapping in a tail-to-tail manner. An "exon trap" strategy was used
      to identify the overlap phenomenon. By using RT-PCR and 3' RACE we have
      identified two major PKN transcripts that are produced by alternative
      polyadenylation. The 3' end of the short PKN transcript overlaps the 3'
      untranslated region of the EP1 gene with approximately 280 bp, while the long PKN
      transcript overlaps the whole EP1 gene. Remarkably, none of the three transcripts
      originating from this locus display the consensus AAUAAA polyadenylation signal.
      The last seven exons of the PKN gene, corresponding to the last third of the PKN
      cDNA, have been recognised in 7.2 kb of continuous genomic sequence that we have
      collected from the EP1/PKN genetic locus. The 3' part of the PKN gene is highly
      fragmented and its intron/exon organisation is reminiscent of that of the
      Drosophila protein kinase C gene. The possibility of a natural antisense
      regulation of these genes is discussed.

PMID- 8858106
TI  - The ras-related protein Ral is monoglucosylated by Clostridium sordellii lethal
      toxin.
AB  - Clostridium sordellii lethal toxin (LT), a cytotoxin which causes preferential
      destruction of the actin cytoskeleton, has been recently identified as
      glucosyltransferase to modify the low molecular mass GTPases Rac, Ras and Rap. We
      report here on LT produced by C. sordellii strain 6018 which glucosylates in
      addition to Rac, Ras and Rap the Ral protein. LT from strain VPI9048 however does
      not glucosylate Ral. Besides recombinant Ral, cellular Ral is also substrate. In
      the GDP-bound form, Ral is a superior substrate to the GTP form. Acceptor amino
      acid for glucose is threonine-46 which is equivalent to threonine-35 in H-Ras
      located in the effector region. The Ral-glucosylating toxin is a novel isoform of
      Ras-modifying clostridial cytotoxins.

PMID- 8858107
TI  - The metastasis suppressor candidate nucleotide diphosphate kinase NM23
      specifically interacts with members of the ROR/RZR nuclear orphan receptor
      subfamily.
AB  - We have cloned proteins that interact with the nuclear orphan receptor RZR beta
      using the yeast two-hybrid system. We identified, amongst a number of other
      genes, the nucleoside diphosphate kinase (NDPK)-2 also known as Nm23-2, c-myc
      regulatory factor PuF and differentiation inhibitory factor, RZR beta
      specifically interacts with Nm23-2 but not with the closely related tumor
      metastasis suppressor candidate gene product Nm23-1. In contrast ROR alpha
      interacts with both Nm23 proteins. These findings were corroborated by in vitro
      interaction assays based on GST-pulldown experiments. With-n-myc we propose a
      candidate gene regulated by ROR alpha/RZR beta and Nm23, based on the finding
      that the respective DNA binding sites in the first intron are conserved in
      several mammalian species.

PMID- 8858108
TI  - Localization of nitric oxide synthase in human skeletal muscle.
AB  - The present study investigated the cellular localization of the neuronal type I
      and endothelial type III nitric oxide synthase in human skeletal muscle. Type I
      NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all
      muscle fibres. Stronger immunoreactivity was expressed in the sarcolemma as well
      as the cytoplasm of type I muscle fibres. NADPH diaphorase activity confirmed a
      higher level of NO synthase activity in the sarcolemma as well as the cytoplasm
      of type I muscle fibers. Histochemical staining for cytochrome oxidase showed a
      staining pattern similar to that observed for type I NO synthase immunoreactivity
      and NADPH diaphorase activity. Type III NO synthase immunoreactivity was observed
      both in the endothelium of larger vessels and of microvessels. The results
      establish that human skeletal muscle expresses two different constitutive
      isoforms of NO synthase in different cellular compartments and suggest that NO
      may have specific actions in relation to its site of production. The localization
      of type I NO synthase in the vicinity of mitochondria supports a specific action
      of NO on mitochondrial respiration, whereas the localization of type III NO
      synthase in vascular endothelium is consistent with a role for NO in the control
      of blood flow in human skeletal muscle.

PMID- 8858109
TI  - Establishment and characterization of a Chinese hamster ovary cell line, CHO-4J,
      stably expressing a number of Na+/I- symporters.
AB  - The cDNA of the Na+/I- symporter playing a key role in thyroid iodide transport
      was cloned very recently. To characterize its function, we transfected the Na+/I-
      symporter gene into Chinese hamster ovary (CHO) cells and established a cell line
      stably expressing a number of rat Na+/I- symporters, named CHO-4J. Iodide uptake
      was dependent on [Na+] and reached a plateau within 30 min. Kinetic studies
      revealed that the K(m) for iodide was 35 microM, similar to that of FRTL-5
      thyroid cells. The maximal velocity (Vmax) at cell protein level was 6-10-fold
      higher than in FRTL-5 cells and that at single cell level was approximately 1000
      fold higher. CIO4- and SCN- dose-dependently inhibited iodide uptake in a
      competitive manner. The Ki was 1.5 and 16 microM, respectively. Iodide efflux
      from CHO-4J cells was apparently slower (t1/2 = 15 min) than FRTL-5 cells (t/2 =
      2 min). Electrophysiological characteristics were examined using the whole cell
      patch clamp technique. Rapid inward current was observed when CHO-4J cells were
      perfused with 50-1000 microM Nal, suggesting a transport stoichiometry of at
      least 2 Na+ per I-. The current-voltage relation revealed that this current was
      membrane potential-dependent. The reversal potential was very close to that of
      Na+ in agreement with dependency on the Na+ electrochemical gradient. CHO-4J
      cells with a slow iodide efflux, expressing a number of Na+/I-symporters whose
      characteristics are identical to those of FRTL-5 cells will function as a new
      tool for sensitive of iodide uptake.

PMID- 8858110
TI  - Identification of glycyrrhizin-binding protein kinase as casein kinase II and
      characterization of its associated phosphate acceptors in mouse liver.
AB  - Two forms (G-I and G-II kinases) of casein kinase II(CK-II) in a partially
      purified CK-II fraction (Mono Q fraction) of mouse liver were separated by means
      of glycyrrhizin (GL)-affinity column chromatography. Biochemical characterization
      revealed that these two GL-binding kinases were identical to CK-II. Two phosphate
      acceptors [p99 (pI 7.0) and p56] copurified with CK-II were identified as ERp99
      (Hsp-90-family protein) and calreticulin, respectively. Another protein [p100 (pI
      9.0)], which crossreacted with anti-serum against human glucocorticoid receptor
      (GR), was associated with ERp99. Phosphorylation of p99 [a hetero-complex of p99
      (pI 7.0) and p100 (pI 9.0)] and p56 by CK-II in vitro was stimulated
      significantly by low levels (1-3 microM) of GL, but inhibited significantly at
      doses above 20 microM. However, no effect of GL on autophosphorylation of ERp99
      was detected. The data provided here suggest that GL can regulate CK-II-mediated
      phosphorylation involved in the GL-induced biological effects in mammalian cells.

PMID- 8858111
TI  - O-linked glycosylation modifies CD44 adhesion to hyaluronate in colon carcinoma
      cells.
AB  - CD44 alternative splicing patterns differ between normal and malignant tissue,
      and accordingly, modulation of CD44 splicing has received the most attention in
      studies that have examined the role of CD44 in tumor progression. Many
      investigators have examined functional differences between individual CD44
      alternative splice variants. However, specific CD44 isoforms function uniquely
      depending on the type of cell on which they are expressed, thereby suggesting
      that additional tissue-specific mechanisms regulate CD44 function. In the present
      study we have demonstrated that colon carcinoma cells modify CD44 with O-linked
      glycosyl groups, and blockade of this glycosylation enhances their CD44-mediated
      adhesion to hyaluronate. This enhancement is attributable principally to CD44H
      (CD44s) rather than high molecular weight CD44 variants. Use of site-directed
      mutant CD44H cDNA transfectants demonstrated that CD44 O-linked glycosylation
      modulates interaction between hyaluronate and the B loop domain of CD44. The
      influence of glycosylation on CD44 function in colon carcinoma cells is specific
      to the presence of O-linked sugars; inhibition of N-linked glycosylation had
      minimal influence on CD44 function. These findings indicate that O-linked
      glycosylation may be as important as alternative splicing in the regulation of
      CD44 function and the broad spectrum of biological processes attributed to it,
      including normal development, tumor metastases, and lymphocyte function.

PMID- 8858112
TI  - Phosphorothioate-capped antisense oligonucleotides to Ras GAP inhibit cell
      proliferation and trigger apoptosis but fail to downregulate GAP gene expression.
AB  - We have studied the effects of an antisense oligonucleotide to Ras GAP in
      leukaemia cell lines. When terminal phosphorothioate linkages were introduced
      into this oligonucleotide, it caused major growth inhibition and apoptosis in the
      chronic myeloid leukaemia (CML) cell line K562, but had little effect on the
      promyelocytic leukaemia cell line HL60. Neither the expression of Ras GAP mRNA
      nor p120 GAP protein was downregulated by the antisense oligonucleotide,
      suggesting a non-antisense mechanism for growth inhibition. The antisense
      oligonucleotide contained GGC triplets which have previously been reported to
      inhibit the activity of p210bcr-abl both in vitro and in vivo. However, cellular
      phosphotyrosine levels were found to be unaffected, suggesting that the activity
      of p210bcr-abl was normal and that the antisense oligonucleotide may be
      interacting aptamerically with a different cellular protein. Since K562 is very
      resistant to apoptotic cell death, the identity of the putative target molecule
      would be of considerable interest.

PMID- 8858113
TI  - Naturally occurring protease inhibitors potent against the human immunodeficiency
      virus.
AB  - Inhibition of protease enzymes can render the human immunodeficiency virus (HIV)
      non-infectious in vitro. To enhance bioavailability and pharmacokinetic activity,
      86 new blocking agents against HIV-I protease are derived by screening genome
      sequences from naturally occurring enzymes. The new agents are rank-ordered
      according to their chemical distance from a known set of HIV-protease inhibitors;
      the scoring methods have previously demonstrated 92% success in classifying a
      given amino acid sequence prior to testing for antiviral potency. The work has:
      1) generalized the empirical work on HIV-PR to more than double the number of
      published peptides for blocking PR activity; 2) rank-ordered the inhibitors
      according to their chemical distance from the consensus sequence; 3) identified
      at least 28 gut enzymes with known bioavailability (> 10%) in vivo; 4) classified
      the family groupings of protease inhibitors in a hierarchical tree. Compared to
      the library of best known peptides, 19 of the natural sequences are closer to the
      consensus library than existing inhibitors.

PMID- 8858114
TI  - Defective degradation of leukotrienes in peroxisomal-deficient human hepatocytes.
AB  - Chain-shortening via beta-oxidation from the omega-end has been recognized as the
      major pathway for the degradation of the biologically active cysteinyl
      leukotrienes as well as LTB4. The metabolic compartmentation of this pathway was
      investigated in peroxisomal-deficient (Zellweger syndrome) and normal human
      hepatocytes. Leukotriene metabolism was studied in isolated hepatocytes by
      incubation with omega-carboxy-[3H]LTE4 as well as omega-carboxy-[3H]LTB4.
      Analysis was done by HPLC, UV-detection and radioactivity measurements.
      Incubation of normal hepatocytes with omega-carboxy-[3H]LTE4 or omega-carboxy
      [3H]LTB4 resulted in the formation of the corresponding beta-oxidation products,
      whereas beta-oxidation derivatives were not detected as products formed by
      peroxisome-deficient human hepatocytes. These results underline the essential
      contribution of peroxisomes in the catabolism and inactivation of cysteinyl
      leukotrienes and LTB4 in humans.

PMID- 8858115
TI  - Intersubunit interactions in the bovine mitochondrial complex I as revealed by
      ligand blotting.
AB  - Bovine mitochondrial complex I (NADH: ubiquinone oxidoreductase) is composed of 3
      structural domains, designated FP (flavoprotein, 3 subunits), IP (iron-sulfur
      protein, 7-8 subunits) and HP (hydrophobic protein, > 30 subunits). IP intervenes
      between FP and HP, and in complex I its 75 kDa subunit appears to interact with
      the 51 kDa subunit of FP. In this study, we show by the technique of ligand
      blotting that isolated IP binds (a) only to the 51 kDa subunit of FP, and (b) to
      the 42, 39, 23, 20 and 16 kDa subunits of HP. Because a 23 kDa and a 20 kDa
      subunit of complex I are potential iron-sulfur proteins, these and our previous
      results are consistent with the following possible path of electrons in complex
      I: NADH-->51 and 24 kDa subunit of FP-->75 kDa subunit of IP-->23 and 20 kDa
      subunits of HP-->ubiquinone.

PMID- 8858116
TI  - The inhibition of estrogen receptor-mediated responses by chloro-S-triazine
      derived compounds is dependent on estradiol concentration in yeast.
AB  - The chloro-S-triazine derived compounds atrazine, atrazine desisopropyl,
      cyanazine, and simazine are commonly used herbicides. These compounds do not have
      estrogenic activity in yeast expressing human estrogen receptor (hER) and an
      estrogen-sensitive reporter. In the presence of a concentration of estradiol (20
      nM) that induced maximal reporter activity in yeast, the triazines did not
      inhibit reporter activity. However, the triazines decreased reporter activity in
      a dose dependent manner in the presence of a submaximal concentration of
      estradiol (0.5 nM). The estradiol-dependent activity of a mutant hER lacking the
      amino terminus was not inhibited by the triazines in yeast. Competition binding
      assays demonstrated that the triazines displaced radiolabeled estradiol from
      recombinant hER. These results suggest that the ability of the triazines to
      inhibit estrogen receptor-mediated responses in yeast occur through their
      interaction with hER and is dependent on the concentration of estradiol.

PMID- 8858117
TI  - A G-to-A substitution at nucleotide position 3316 in mitochondrial DNA is
      associated with Japanese non-insulin-dependent diabetes mellitus.
AB  - By directly sequencing amplified DNA from 30 patients with non-insulin-dependent
      diabetes mellitus (NIDDM) who had diabetic family members, we identified a G-to-A
      mutation at np 3316 in the ND-1 gene of the mitochondrial DNA (mtDNA). DNA from
      254 patients with NIDDM or impaired glucose tolerance (IGT), from 154 patients
      with insulin dependent diabetes mellitus (IDDM) and from 207 non-diabetic control
      subjects was screened for this substitution. The mutation existed in 5 of 254
      Japanese NIDDM or IGT patients (2.0%), but not in other subjects. Its prevalence
      was significantly higher in NIDDM than in other patients or non-diabetic control
      subjects. The association of the G-A mutation at np 3316 with glucose intolerance
      suggests the importance of this area for the development of diabetes.

PMID- 8858118
TI  - Evidence that the human homologue of a rat initiation factor-2 associated protein
      (p67) is a methionine aminopeptidase.
AB  - Previously, we cloned a human cDNA encoding a protein which has a 92% amino acid
      sequence identity to a rat initiation factor-2 associated protein (p67). Rat p67
      plays an important role in translational regulation by preventing the
      phosphorylation of the alpha subunit of initiation factor-2. Interestingly,
      several lines of indirect evidence suggested that this protein may also function
      as a methionine aminopeptidase (MetAP). To test this hypothesis, we expressed the
      human cDNA in a baculovirus system, purified it to homogeneity and characterized
      it. Using 13 different peptide substrates, we found that the human p67 has a
      similar substrate specificity with other MetAPs. Kinetic analyses revealed that
      the Kcat/K(m) values of the human MetAP on two representative substrates are
      similar to those of yeast and porcine MetAPs. Furthermore, we found that this
      enzyme, like other MetAPs, is also a cobalt-dependent metalloenzyme.

PMID- 8858119
TI  - An in vivo cytokine and endotoxin-independent pathway for induction of nitric
      oxide synthase II mRNA, enzyme, and nitrate/nitrite in alveolar macrophages.
AB  - Dibutyryl cyclic AMP (DB-cAMP, 0.1 and 1.0 mg/kg) and the purine-2-receptor
      agonist methyl-thio-ATP (MT-ATP mg/kg) given by intratracheal (i.t.)
      administration to rats two hr before bronchoalveolar lavage (BAL) increased iNOS
      mRNA to be equal to or greater than that produced by i.t. LPS, without eliciting
      neutrophil infiltration into the alveolar space or the upregulation of tumor
      necrosis factor alpha (TNF alpha). Translation of DB-cAMP and MT-ATP stimulated
      iNOS mRNA into protein and activation of iNOS to produce RNI was slower than that
      resulting from LPS-stimulated iNOS mRNA. Diethyldithiocarbamate (5 mg/kg, i.t.) a
      sequestrant of reactive oxygen intermediates and an inhibitor of NFkappaB
      attenuated LPS-induced upregulation of iNOS mRNA without affecting that produced
      by DB-cAMP or MT-ATP. We conclude that an LPS and cytokine-independent pathway of
      transcription of iNOS mRNA exists in vivo, which can be directly activated by DB
      cAMP and purine-2 receptor stimulation. It is possible that the increase in iNOS
      found in asthmatic patients and those with other diseases that are treated with
      drugs which affect the cAMP and purine systems may be iatrogenic rather than
      pathogenetic in origin.

PMID- 8858120
TI  - Contractile agonists preferentially activate CL- over K+ currents in arterial
      myocytes.
AB  - Simultaneous patch-clamp and Ca2+ fluorescence measurements have revealed
      depolarising oscillations in the membrane potential of arterial (pulmonary)
      myocytes in response to adenosine 5'-triphosphate (ATP) and endothelin-1 (ET-1).
      These oscillations (i) are due to the preferential activation of Ca(2+)-activated
      Cl-, over K+ currents, (ii) occur through a mechanism involving Ca2+ release from
      intracellular Ca2+ stores and (iii) are likely to promote constriction. These
      results provide a novel perspective into the relative contribution and importance
      of Ca2+ activated Cl- and K+ channels in controlling membrane potential of
      arterial smooth muscle in response to contractile agonists.

PMID- 8858121
TI  - In vitro and in vivo evaluation of an endothelin inhibitor reveals novel K+
      channel opening activity.
AB  - A low molecular weight endothelin (ET-1) inhibitor (Ex. 127, European Patent
      Application 404 525 A2, Takeda Chemical Ind., 1991), CGS 26061, was synthesized
      and evaluated to determine its mechanism of action. CGS 26061 (10 microM) failed
      to inhibit binding of [125I]ET-1 in porcine thoracic aorta and was without effect
      on ET-1-induced [3H]inositol phosphate accumulation in A7r5 cells. However, CGS
      26061 relaxed porcine coronary arterial rings precontracted with ET-1. In
      addition, contractions to PGF2 alpha and low K+ (20 mM) but not high K+ were
      attenuated, suggesting that CGS 26061 (1, 10 microM) is a potassium channel
      opener. Patch-clamp experiments confirmed the K+ channel activity (0.1-10
      microM). The originally re ported inhibition of ET-1-induced pressor responses by
      Ex. 127 (CGS 26061) was not replicated in the anesthetized dog or conscious rat
      nor was it shown to be antihypertensive in SHR. These data have identified CGS
      26061 as a novel K+ channel opener with a unique cardiovascular profile.

PMID- 8858122
TI  - CFTR is involved in membrane endocytosis but not in fluid-phase and receptor
      mediated endocytosis in human respiratory epithelial cells.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) protein has been
      reported to be a cAMP-regulator of plasma membrane recycling in epithelial cells
      overexpressing CFTR. To assess its role in the different endocytic processes in
      human respiratory epithelial cells, the rates of internalization of membrane,
      fluid-phase and receptor-mediator tracers were compared, under control conditions
      and after treatment with the cAMP agonist forskolin in normal and cystic fibrosis
      (CF) cells. In both control and treated-cells, CFTR was only present in the
      plasma membrane of normal but not in CF cells. Similarly, activation of Cl-
      efflux only occurred in normal and not in CF-treated cells. The rate of membrane
      endocytosis was significantly decreased by 35% in normal treated-cells, whereas
      it was not significantly decreased (12%) in CF-treated cells. Upon forskolin
      treatment, the decrease of the rate of both fluid-phase and receptor-mediated
      endocytosis was not significantly different between normal and CF cells. These
      results demonstrate that CFTR is involved in membrane endocytosis but not in
      fluid-phase and receptor-mediated endocytosis in human respiratory epithelial
      cells.

PMID- 8858123
TI  - A new mutation destroying disulphide bridging in the C-terminal domain of
      lipoprotein lipase.
AB  - Lipoprotein lipase (LPL) is one of two intravascular lipases involved in the
      lipolysis of the triglyceride core of circulating lipoproteins. The occurrence of
      patients with genetic deficiencies has provided insight into the structure and
      function relationships of this lipase. It is now known that LPL manifests a two
      domain structure with the N-terminal domain of greater structural and functional
      significance as it contains the active site and interfacial binding motifs. We
      report on a Cys418Tyr substitution in the C-terminal domain which disrupts the
      only disulphide bridge in the region and is associated with catalytic deficiency
      in post-heparin plasma. This result was unexpected as previous in vitro
      assessment of the functional significance of disulphide bridging had shown that
      while the 3, N-terminal disulphides were critical for enzyme function, loss of
      the only C-terminal disulphide minimally affected catalytic activity. We
      generated the Cys418Tyr mutant by site-directed mutagenesis and show that it
      manifests 48% of normal activity in vitro, while the companion variants,
      Cys438Ser and Cys418Ser-Cys438Ser, are less affected with activities at 76% and
      78% of normal.

PMID- 8858124
TI  - Oxidation of porphyrinogens by horseradish peroxidase and formation of a green
      pyrrole pigment.
AB  - When humans or plants are exposed to certain chemicals which interfere with heme
      biosynthetic enzymes, porphyrinogen intermediates accumulate and are oxidized to
      cytotoxic porphyrins. Here we have investigated the role of peroxidases in
      porphyrinogen oxidation. Horseradish peroxidase (HRP) rapidly oxidizes
      uroporphyrinogen to uroporphyrin and this is inhibited by ascorbic acid. HRP also
      oxidizes deuteroporphyrinogen (a synthetic porphyrin similar to
      protoporphyrinogen), but the yield of porphyrin is lower than with
      uroporphyrinogen as substrate. This low yield is in part due to a rapid, HRP
      dependent conversion of deuteroporphyrin (but not uroporphyrin) to a green
      compound with spectral characteristics of a chlorin with a large peak at 638 nm.
      This reaction requires addition of a sulfhydryl reductant such as glutathione and
      is inhibited by ascorbic acid. These findings suggest that cellular peroxidases
      and ascorbic acid levels may play a role in modifying the phototoxic
      tetrapyrroles which accumulate in plants and humans after certain environmental
      exposures.

PMID- 8858125
TI  - Dopamine D2 receptor dimers and receptor-blocking peptides.
AB  - Dopamine D2 receptors exist as dimers in whole cell lysate, crude membranes
      prepared from human caudate, and following solubilization and immunoprecipitation
      of the receptor from these tissues. Photoaffinity labelling experiments confirmed
      that D2 receptors exist either as monomers that are selective targets for
      spiperone or as dimers that are targets for nemonapride. Incubation of D2 dimers
      with peptides derived from the putative transmembrane (TM) domains of the D2
      receptor, or incubation under high temperatures or low pH resulted in the
      dissociation of the dimer to monomer. D2-TM peptides were unable to dissociate
      dopamine D1 and serotonin 5-HT1B receptor dimers, suggesting that receptor dimers
      are formed by specific intermolecular noncovalent interactions involving TM
      regions. This opens a path to new selective therapeutic receptor-blocking
      compounds based on this principle of mimicking transmembrane portions of
      neurotransmitter receptors.

PMID- 8858126
TI  - Recombinant alpha 1(VIII) collagen chains form homotrimers in vitro.
AB  - Type VIII collagen, a member of the short chain collagen family, is expressed in
      large blood vessels and in the subendothelium and mesangium of the glomerulus.
      While two genetically distinct type VIII collagen chains, alpha 1 and alpha 2,
      have been identified, it is not known whether type VIII collagen exists as
      homotrimers or heterotrimers. To determine whether alpha 1(VIII) collagen chains
      can associate to form homotrimers, a full length human alpha 1(VIII) collagen
      cDNA was generated by overlap extension PCR and used as a substrate for coupled
      in vitro transcription/translation. A translation product of 80kDa, the predicted
      size of alpha 1(VIII) collagen, was identified by autoradiography of SDS-gels
      containing radiolabelled translation products. Sensitivity of the in vitro
      translated protein to digestion with bacterial collagenase and trypsin and the
      size of the proteins generated by these digestions provide evidence that alpha
      1(VIII) collagen can participate in the formation of homotrimers.

PMID- 8858127
TI  - Electron paramagnetic resonance (EPR) studies on hydrogenase-1 (HYD1) purified
      from a mutant strain (AP6) of Escherichia coli enhanced in HYD1.
AB  - Hydrogenase-1 (HYD1), overexpressed by twofold, has been purified to homogeneity
      and to a high specific activity from a mutant strain (AP6) of Escherichia coli
      which lacks hydrogenase-2. Plasma emission spectroscopy indicated that 0.93 atom
      of nickel and 11.4 iron atoms were present in HYD1. EPR studies on the as
      isolated HYD1 detected a complex 3Fe-4S signal and a Ni(III) species. Reduction
      with hydrogen gas caused disappearance of both the 3Fe-4S cluster and initial
      Ni(III) signals. At the same time the EPR signature (small g = 2.19 signal) of
      the activated hydrogenase appeared. The detection of a 4Fe-4S cluster signal was
      noted. Reduction of HYD1 with sodium dithionite caused all nickel signals to
      disappear. The 4Fe-4S complex intensity was slightly increased. The EPR responses
      in the three oxidation-reduction states are consistent with other known (NiFe)
      hydrogenases.

PMID- 8858128
TI  - Reevaluation of superoxide scavenging activity of dihydrolipoic acid and its
      analogues by chemiluminescent method using 2-methyl-6-[p-methoxyphenyl]-3,7
      dihydroimidazo-[1,2-a]pyrazine-3-one (MCLA) as a superoxide probe.
AB  - The superoxide scavenging activity of dihydrolipoic acid and its analogues has
      been reevaluated by a chemiluminescence method using MCLA as a superoxide
      indicator. The results demonstrated that all the compounds having the thiol
      chromophore in the molecule showed scavenging activity toward superoxide. The
      short-chain analogue, tetranor-dihydrolipoic acid, showed almost the same
      scavenging activity as that of dihydrolipoic acid; however, bisnor-dihydrolipoic
      acid showed weaker scavenging activity than that of dihydrolipoic acid. The
      reaction rates of dihydrolipoic acid, bisnor-dihydrolipoic acid, and tetranor
      dihydrolipoic acid were calculated from the competitive inhibition of MCLA
      superoxide reaction. Thus, it was concluded that dihydrolipoic acid and the
      analogues are good scavengers of superoxide radical anion.

PMID- 8858129
TI  - In vivo characteristics and localisation of carotenoid pigments in psychrotrophic
      and mesophilic Micrococcus roseus using photoacoustic spectroscopy.
AB  - Photoacoustic spectra of cells of M. roseus were recorded to study the in vivo
      characteristics and localisation of the carotenoid pigments in these cells. The
      PA spectra indicated that both the psychrotrophic and mesophilic strains had
      similar chromophores. The cis carotenoids were prominent in the psychrotrophic
      M.roseus whereas shorter polyenes were more prominent in mesophilic M.roseus.
      Further, depth profiling photoacoustic studies revealed that in both the strains
      of M.roseus the bulk of the chromophore was associated with the cell membrane.

PMID- 8858130
TI  - Structural requirements of taxoids for nitric oxide and tumor necrosis factor
      production by murine macrophages.
AB  - Taxol (paclitaxel), a microtubule stabilizer with antitumor activity, mimics the
      actions of lipopolysaccharide (LPS) on murine macrophages (M phi). In the present
      study, a variety of synthetic analogs of paclitaxel were examined for their
      potencies to induce nitric oxide (NO) and tumor necrosis factor (TNF) production
      by peritoneal M phi from LPS-responsive C3H/HeN, and LPS-hyporesponsive C3H/HeJ
      mice, and by M phi-like LPS-responsive J774.1 and its mutant LPS-hyporesponsive
      J7.DEF3 cells. In this structure-activity relationship study, we found that (i)
      the benzoyl group at the C-3' position of paclitaxel is the most important site
      to activate C3H/HeN M phi; (ii) the phenyl group at C-3' is not a requisite for
      the activity; (iii) there is good correlation between NO and TNF production by
      the M phi in response to compounds, except for the analogs having a tert
      butoxycarbonyl (10-acetyldocetaxel) or a thiophene-2-carbonyl group at C-3'-N
      instead of a benzoyl group, which is more dominant in TNF than in NO production;
      (iv) the compounds tested induce neither NO nor TNF production by C3H/HeJ M phi;
      (v) active compounds to C3H/He M phi induce TNF production by J7.DEF3 cells as
      well as J774.1 cells; and (vi) 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. These data also suggest that the binding of taxoid/LPS
      to tubulin is not essential for the M phi activation.

PMID- 8858131
TI  - Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T
      transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene.
AB  - Type I thanatophoric dysplasia (TD) is typically a lethal neonatal dwarfism, but
      a limited number of cases of type I TD cases survive more than one year,
      suggesting genetic heterogeneity. In this study, we analyzed the fibroblast
      growth factor receptor 3 (FGFR3) gene in 5 Japanese cases of type I TD with
      clinical symptoms ranging from lethal to long-survival. In every case, nucleotide
      sequence analysis of cDNA revealed a C to T transition at nucleotide 742 (C742T)
      in one allele of the FGFR3 gene, suggesting that type I TD is a rather
      homogeneous genetic condition, irrespective of clinical course. No association
      was found between C742T and C882T, although both nucleotides changes were from
      CpG dinucleotide in a near location.

PMID- 8858132
TI  - Identification of domains of the cardiac inward rectifying K+ channel, CIR,
      involved in the heteromultimer formation and in the G-protein gating.
AB  - The cardiac inward rectifying K+ channel, CIR, and the strongly inward rectifying
      K+ channel, IRK1, exhibited clearly different electrophysiological properties.
      CIR formed a heteromultimer with the G-protein coupled inward rectifying K+
      channel, GIRK1, whereas IRK1 did not, and CTR homo- and heteromultimeric channels
      were activated by G-protein beta 1 gamma 2 subunits (G beta 1 gamma 2), whereas
      IRK1 channels were not. To identify the domains of CIR involved in the
      heteromultimer formation with GIRK1 and in the G beta 1 gamma 2 gating, we
      constructed chimeras of CIR and IRK1 and examined their electrophysiological
      properties. The channels were divided into three domains; the N-terminal
      cytoplasmic domain, the C-terminal cytoplasmic domain and the residual core
      domain. By the analysis, it was concluded that (i) the core region of CIR, but
      not the N and C cytoplasmic domains, is critical for the heteromultimer formation
      with GIRK1; and (ii) the N and C terminal cytoplasmic regions of CIR are
      sufficient for the G beta 1 gamma 2 gating. We also showed that the N terminal
      cytoplasmic region is involved in the determination of the rate of activation
      upon hyperpolarization.

PMID- 8858133
TI  - Role for Bcl-xL in the regulation of apoptosis by EGF and TGF beta 1 in c-myc
      overexpressing mammary epithelial cells.
AB  - We previously showed that TGF alpha synergizes with c-myc in mammary
      tumorigenesis through inhibition of Myc-induced apoptosis. We therefore examined
      the effects of growth factors on apoptosis induction in several cell lines from
      MMTV-myc mammary tumors. When EGF was withdrawn or TGF beta 1 was added, cells
      became apoptotic after 15 h (by ELISA and morphology). Northern and Western
      analysis revealed high levels of Bax and p53, and low or undetectable levels of
      Bcl-2 and Bcl-xS under all treatment condition. In contrast, Bcl-xL expression
      was highest in the presence of EGF or TGF alpha, with a significant reduction
      upon removal of EGF or exposure to TGF beta. In mouse mammary tumors, the
      relative Bcl-xL/Bax ratio was higher in TGF alpha/Myc double transgenics than in
      Myc single transgenics, in agreement with the in vitro data. Our results suggest
      a role for Bcl-xL in the regulation of apoptosis by EGF and TGF beta in mammary
      epithelial cells.

PMID- 8858134
TI  - Rapid identification of homeodomain binding sites in the Wnt-5a gene using an
      immunoprecipitation strategy.
AB  - Here we describe an immunoprecipitation approach for identifying homeodomain
      binding sites within uncharacterized genomic sequences of a putative downstream
      target gene, Wnt-5a. Immunoprecipitation of Wnt-5a genomic fragments was
      performed using a purified Msx1 homeodomain polypeptide (Msx1) and its
      corresponding antisera (alpha-Msx1). This resulted in isolation of three
      fragments containing multiple DNA binding sites for Msx1, as confirmed by DNA
      binding studies. The three fragments were contiguous within a 3.4 kb intronic
      sequence of Wnt-5a. Moreover, at least one of the Msx1 sites has been conserved
      throughout evolution, suggesting that these sites may comprise or contribute to a
      regulatory element for Wnt-5a. We propose that the immunoprecipitation strategy
      permits a rapid, initial approach for identifying functionally-relevant
      homeodomain binding sites within target genes whose regulatory sequences have not
      yet been previously elucidated.

PMID- 8858135
TI  - Regulation of tumor necrosis factor-and Fas-mediated apoptotic cell death by a
      novel cDNA TR2L.
AB  - A novel cDNA, TR2L, isolated from murine NIH 3T3 fibroblasts, was found to
      modulate tumor necrosis factor (TNF)-mediated apoptosis in murine L929
      fibrosarcoma cells. The full-length cDNA (853 bp) encodes a predicted coding
      region of 56 amino acids (6.3 kD), with 53.6% identity to the C-terminus of rat
      transcriptional activator FE65. When expressed stably in L929 cells, TR2L protein
      inhibited TNF cytotoxic response. In contrast, TR2L enhanced anti-Fas
      antibodies/actinomycin D (ActD)-mediated L929 apoptosis. Alteration of TR2L
      function occurred by tagging this protein with a 6xHis fragment to the N-terminus
      (designated 6xH-TR2L). L929 cells which stably expressed 6xH-TR2L acquired a
      significantly enhanced TNF apoptotic response and increased genomic DNA
      fragmentation compared to control cells. Enhanced cell death also occurred in
      these 6xH-TR2L-expressing cells under serum starvation conditions. In contrast,
      the anti-Fas/ActD-mediated apoptosis was blocked by the 6xH-TR2L protein.
      Functional role of TR2L protein in regulation of cancer cell susceptibility to
      TNF-and Fas ligand-mediated apoptosis is suggested.

PMID- 8858137
TI  - Potential biosynthetic connections between the two cannabimimetic eicosanoids,
      anandamide and 2-arachidonoyl-glycerol, in mouse neuroblastoma cells.
AB  - Anandamide (arachidonoyl-ethanolamide, AnNH) and 2-arachidonoyl-glycerol (2-AG)
      have been suggested to act as endogenous agonists at the brain cannabinoid
      receptor, and their biosynthetic and degradative mechanisms in nervous tissues
      and cells have also been partially elucidated. Here we present evidence for the
      presence, in mouse N18TG2 neuroblastoma cells, of enzymatic activities
      potentially responsible for the biosynthesis of AnNH and 2-AG from a common
      phospholipid precursor. Cell homogenates were shown to catalyze: (a) the transfer
      of an arachidonoyl moiety from the sn-1 position of sn-1,2-di-arachidonoyl
      phosphatidylcholine (AAPC) to phosphatidyl-ethanolamine (PE) to form N
      arachidonoyl-PE (N-ArPE) and sn-1-lyso-2-arachidonoyl-PC (lyso-APC), (b) the
      hydrolysis of N-AtPE to AnNH, (c) the hydrolysis of lyso-APC to 2-AG, (d) the
      hydrolysis of AAPC to sn-1,2-di-arachidonoyl-glycerol (AAG), and (e) the
      hydrolysis of AAG to 2-AG. From these findings it is possible to suggest that
      AAPC may serve as precursor for both AnNH and 2-AG biosynthesis through three
      different pathways.

PMID- 8858136
TI  - Molecular cloning of rat macrophage-stimulating protein and its involvement in
      the male reproductive system.
AB  - Macrophage-stimulating protein (MSP), a member of the hepatocyte growth factor
      family, is a ligand for receptor tyrosine kinase STK/RON. Here we isolated a full
      length cDNA of rat MSP and a partial cDNA of rat STK/RON, then characterized
      their expression in the male reproductive system. In situ hybridization revealed
      that MSP mRNA was localized to spermatogonia and spermatocytes in the testis and
      the epithelium lining the lumen of the epididymis. On the other hand, RT-PCR
      analysis showed that STK/RON mRNA was expressed in sperm collected from both
      testis and epididymis. These findings suggest that locally produced MSP may play
      a vital role in germ cell-germ cell interaction during spermatogenesis as well as
      in the acquisition of sperm motility and/or fertilizing capacity in the
      epididymis. Our findings reveal new possible roles of the MSP-STK/RON signaling
      pathway.

PMID- 8858139
TI  - Acasp, a gene encoding a cathepsin D-like aspartic protease from the hookworm
      Ancylostoma caninum.
AB  - Intestinal infection with the zoonotic hookworm Ancylostoma caninum can provoke
      human eosinophilic enteritis. A cDNA was isolated from A. caninum, using an
      oligonucleotide primer designed to hybridize to the region encoding the
      consensus, catalytic site residues D32TGSSNLW of aspartic proteases. This novel
      cDNA encoded an aspartic protease zymogen of 422 amino acids, exhibiting 47%
      identity to the lysosomal aspartic protease of Aedes aegypti, 46% identity to the
      aspartic protease of Schistosoma japonicum, and 48.5% to human cathepsin D. Its
      deduced structure differed from that of cathepsin D in the loop 2 "flap," which
      holds the substrate at the active site, and by the presence of a COOH-terminal
      extension of approximately 30 residues.

PMID- 8858138
TI  - Interleukin-1 beta activates PI 3-kinase in renal mesangial cells.
AB  - Interleukin-1 beta rapidly stimulates the activation of phosphatidylinositol 3
      hydroxyl kinase in renal mesangial cells. This interleukin-1 beta dependent
      activation is associated with a rapid increase in phosphatidyl inositol 3,4,5
      phosphate in renal mesangial cells. The increase in PI 3-kinase activity is
      inhibited by wortmannin. In addition wortmannin partially inhibited IL-1 beta
      induced PGE2 production and potentiated IL-1 beta induced nitric oxide
      production. These experiments suggest that IL-1 beta can activate PI 3-kinase in
      renal mesangial cells and that the enzyme plays a role in IL-1 beta induced PGE2
      and NO formation in the renal mesangial cell.

PMID- 8858140
TI  - Role of N-terminal domain of streptokinase in protein transport.
AB  - Streptokinase (SK), an extracellular protein of several haemolytic strains of
      Streptococcus, is utilized as a potent thrombolytic agent for the treatment of
      various myocardial disorders. Functional properties of SK remain unchanged when
      the first 13 N-terminal amino acid (aa) residues are removed. At present, role of
      this segment in protein structure function is unclear. skc gene encoding for the
      mature SK and its deletion variant, lacking its first 13 aa residues, were cloned
      and expressed in E. coli. Full length SK, deprived of any leader sequences, was
      able to translocate slowly, across the cyto-plasmic and outer membranes of
      E.coli. Whereas, SK derivative, devoid of its first 13 N-terminal aa residues,
      could not do so. Cell fractionation studies as well as genetic evidences
      utilizing alkaline phosphatase fusion, point towards the existence of additional
      information for protein transport, within the N-terminal domain of SK. To further
      investigate the role of this region in protein secretion, genetic fusions were
      created in between full length and 13 aa deleted SK with OmpA leader peptide.
      Studies on kinetics of SK export from E.coli, revealed that translocation of
      protein is 3-4 times faster when the first 13 N-terminal residues of SK are
      intact. On the basis of results obtained, it has been proposed that the N
      terminus of mature SK maintains the export competent status of protein and, thus,
      confer speed and efficiency upon the translocation process of streptokinase.

PMID- 8858141
TI  - A GTPase controlling nuclear trafficking: running the right way or walking
      RANdomly?

PMID- 8858142
TI  - Histone acetylation and chromatin assembly: a single escort, multiple dances?

PMID- 8858143
TI  - Epigenetic programming of developmental genome rearrangements in ciliates.

PMID- 8858144
TI  - NF-kappa B: ten years after.

PMID- 8858145
TI  - Importin provides a link between nuclear protein import and U snRNA export.
AB  - Importin-alpha mediates nuclear protein import by binding nuclear localization
      signals and importin-beta. We find approximately 30% of SRP1p, the yeast importin
      alpha, in a nuclear complex with the Saccharomyces cerevisiae nuclear cap-binding
      protein complex (CBC). Similarly, a large fraction of Xenopus CBC is associated
      with importin-alpha in the nucleus. CBC promotes nuclear export of capped U
      snRNAs and shuttles between nucleus and cytoplasm. The CBC-importin-alpha complex
      binds specifically to capped RNA, suggesting that CBC might shuttle while bound
      to importin-alpha. Strikingly, importin-beta binding displaces the RNA from the
      CBC-importin-alpha complex. Thus, the commitment of CBC for nuclear reentry
      triggers the release of the export substrate into the cytoplasm. We provide
      evidence for a mechanism that ensures that importin-mediated RNA release is a
      specifically cytoplasmic event.

PMID- 8858146
TI  - Role of Tim23 as voltage sensor and presequence receptor in protein import into
      mitochondria.
AB  - Tim23, an essential component of the protein import machinery of the inner
      membrane of mitochondria (TIM complex), forms dimers that display a dynamic
      behavior. Dimer formation is promoted by the membrane potential delta psi.
      Binding of a matrix targeting sequence to Tim23 triggers dimer dissociation.
      Monomeric Tim23 is present when a preprotein chain is in transit across the TIM
      complex. Dimerization of Tim23 is dependent on the second half of its N-terminal
      hydrophilic domain, which is exposed to the intermembrane space. This segment
      contains a heptad leucine repeat motif with a predicted capacity for dimer
      formation. We propose that Tim23 exerts a key function in protein import: Tim23
      dimers formed in response to delta psi act as receptors for matrix targeting
      sequences on the surface of the inner membrane. The ensuring dissociation of
      Tim23 dimer triggers opening of the TIM channel and insertion of the preprotein.

PMID- 8858147
TI  - Identification of neurogenin, a vertebrate neuronal determination gene.
AB  - Several bHLH proteins are involved in vertebrate neurogenesis, but those
      controlling early stages of neuronal determination have not yet been identified.
      Here we describe a novel, NeuroD-related bHLH protein, NEUROGENIN, whose
      expression precedes that of NeuroD in both mouse and Xenopus. Expression of
      Xenopus NEUROGENIN-related-1 (X-NGNR-1) defines the three prospective territories
      of primary neurogenesis. Overexpression of X-NGNR-1 (or NEUROGENIN) induces
      ectopic neurogenesis and ectopic expression of XNeuroD mRNA. Endogenous X-ngnr-1
      expression becomes restricted to subsets of cells by lateral inhibition, mediated
      by X-Delta-1 and X-Notch. The properties of X-NGNR-1 are thus analogous to those
      of the Drosophila proneural genes, suggesting that it functions as a vertebrate
      neuronal determination factor.

PMID- 8858148
TI  - The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA
      replication in cell-free extracts.
AB  - We have cloned a Xenopus Cdc6 homolog (Xcdc6) and characterized its role in DNA
      replication with Xenopus egg extracts. Immunodepletion of Xcdc6 abolishes
      chromosomal replication but not elongation on single-stranded DNA templates.
      Xcdc6 binds to chromatin at the beginning of interphase but disappears from
      chromatin upon initiation of replication. Immunodepletion studies indicate that
      binding of Xcdc6 to chromatin requires Xorc2, a component of the origin
      recognition complex. Moreover, Xmcm3 cannot bind to chromatin lacking Xcdc6,
      suggesting that Xorc2, Xcdc6, and Xmcm3 associate with the DNA sequentially. In
      postreplicative nuclei, Xcdc6 is associated with the nuclear envelope. These
      studies indicate that Xcdc6, is essential for initiation of replication in
      vertebrates and that interaction with the nuclear envelope may regulate its
      function.

PMID- 8858149
TI  - Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis.
AB  - A two-hybrid system was used to screen yeast and human expression libraries for
      proteins that interact with mismatch repair proteins. PCNA was recovered from
      both libraries and shown in the case of yeast to interact with both MLH1 and
      MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly
      elevated mutation rate in a dinucleotide repeat, and the rate was not further
      elevated in a strain also containing a mutation in MLH1. Mismatch repair activity
      was examined in human cell extracts using an assay that does not require DNA
      repair synthesis. Activity was inhibited by p21WAF1 or a p21 peptide, both of
      which bind to PCNA, and activity was restored to inhibited reactions by addition
      of PCNA. The data suggest a PCNA requirement in mismatch repair at a step
      preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may
      reflect linkage between mismatch repair and replication and may be relevant to
      the roles of mismatch repair proteins in other DNA transactions.

PMID- 8858150
TI  - Pdd1p, a novel chromodomain-containing protein, links heterochromatin assembly
      and DNA elimination in Tetrahymena.
AB  - During Tetrahymena conjugation, programmed DNA degradation occurs in two separate
      nuclei. Thousands of germline-specific deletion elements are removed from the
      genome of the developing somatic macronucleus, and the old parental macronucleus
      is degraded by an apoptotic mechanism. An abundant polypeptide, Pdd1p (formerly
      p65), localizes to both of these nuclei at the time of DNA degradation. Here we
      report that, in developing macronuclei, Pdd1p localizes to electron-dense,
      heterochromatic structures that contain germline-specific deletion elements.
      Pdd1p also associates with parental macronuclei during terminal stages of
      apoptosis. Sequencing of the PDD1 gene reveals it to be a member of the
      chromodomain family, suggesting a molecular link between heterochromatin assembly
      and programmed DNA degradation.

PMID- 8858151
TI  - The major cytoplasmic histone acetyltransferase in yeast: links to chromatin
      replication and histone metabolism.
AB  - We have isolated the predominant cytoplasmic histone acetyltransferase activity
      from Saccharomyces cerevisiae. This enzyme acetylates the lysine at residue 12 of
      free histone H4 but does not modify histone H4 when packaged in chromatin. The
      activity contains two proteins, Hat1p and Hat2p. Hat1p is the catalytic subunit
      of the histone acetyltransferase and has an intrinsic substrate specificity that
      modifies lysine in the recognition sequence GXGKXG. The specificity of the enzyme
      in the yeast cytoplasm is restricted relative to recombinant Hat1p suggesting
      that it is negatively regulated in vivo. Hat2p, which is required for high
      affinity binding of the acetyltransferase to histone H4, is highly related to
      Rbap48, which is a subunit of the chromatin assembly factor, CAF-1, and
      copurifies with the human histone deacetylase HD1. We propose that the
      Hat2p/Rbap48 family serve as escorts of histone metabolism enzymes to facilitate
      their interaction with histone H4.

PMID- 8858152
TI  - Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
AB  - Chromatin assembly factor 1 (CAF-1) assembles nucleosomes in a replication
      dependent manner. The small subunit of CAF-1 (p48) is a member of a highly
      conserved subfamily of WD-repeat proteins. There are at least two members of this
      subfamily in both human (p46 and p48) and yeast cells (Hat2p, a subunit of the B
      type H4 acetyltransferase, and Msi1p). Human p48 can bind to histone H4 in the
      absence of CAF-1 p150 and p60. p48, also a known subunit of a histone
      deacetylase, copurifies with a chromatin assembly complex (CAC), which contains
      the three subunits of CAF-1 (p150, p60, p48) and H3 and H4, and promotes DNA
      replication-dependent chromatin assembly. CAC histone H4 exhibits a novel pattern
      of lysine acetylation that overlaps with, but is distinct from, that reported for
      newly synthesized H4 isolated from nascent chromatin. Our data suggest that CAC
      is a key intermediate of the de novo nucleosome assembly pathway and that the p48
      subunit participates in other aspects of histone metabolism.

PMID- 8858153
TI  - Heterochromatin effects on the frequency and duration of LCR-mediated gene
      transcription.
AB  - Locus control regions (LCRs) are responsible for initiating and maintaining a
      stable tissue-specific open chromatin structure of a locus. In transgenic mice,
      LCRs confer high level expression on linked genes independent of position in the
      mouse genome. Here we show that an incomplete LCR loses this property when
      integrated into heterochromatic regions. Two disruption mechanisms were observed.
      One is classical position-effect variegation, resulting in continuous
      transcription in a clonal subpopulation of cells. The other is a novel mechanism
      resulting in intermittent gene transcription in all cells. We conclude that only
      a complete LCR fully overcomes heterochromatin silencing and that it controls the
      level of transcription by ensuring activity in all cells at all times rather than
      directly controlling the rate of transcription.

PMID- 8858154
TI  - A structural model for the HIV-1 Rev-RRE complex deduced from altered-specificity
      rev variants isolated by a rapid genetic strategy.
AB  - A broadly applicable genetic strategy was developed for investigating RNA-protein
      interactions and applied to the HIV-1 Rev protein. By rapidly screening thousands
      of Rev-RNA interactions in Escherichia coli, we isolated Rev suppressor mutations
      that alleviated the deleterious effect of mutations in RRE stem-loop IIB, the
      high affinity RNA-binding site for Rev. All of these suppressor mutations map to
      a single arginine-deficient face of a Rev alpha-helix, and some alter the binding
      specificity of the protein, providing genetic evidence for direct contacts
      between specific Rev amino acids and RNA nucleotides in the RNA complex of Rev.
      The spatial constraints suggested by these data have enabled us to model the
      structure of this complex.

PMID- 8858155
TI  - Crystal structure of a sigma 70 subunit fragment from E. coli RNA polymerase.
AB  - The 2.6 A crystal structure of a fragment of the sigma 70 promoter specificity
      subunit of E. coli RNA polymerase is described. Residues involved in core RNA
      polymerase binding lie on one face of the structure. On the opposite face,
      aligned along one helix, are exposed residues that interact with the -10
      consensus promoter element (the Pribnow box), including four aromatic residues
      involved in promoter melting. The structure suggests one way in which DNA
      interactions may be inhibited in the absence of RNA polymerase and provides a
      framework for the interpretation of a large number of genetic and biochemical
      analyses.

PMID- 8858156
TI  - Human TAFII 105 is a cell type-specific TFIID subunit related to hTAFII130.
AB  - We previously characterized Drosophila and human TAF subunits that make up the
      core TFIID complex found in all cells. Here, we report that differentiated B
      cells contain a novel substoichiometric TAF of 105 kDa not found associated with
      TFIID isolated from other cell types. The cDNA encoding hTAFII105 reveals a
      highly conserved C-terminal domain shared by hTAFII130 and oTAFII110, while the N
      terminal coactivator domain has diverged significantly. All cells tested express
      TAFII105 mRNA, but only B cells contain significant levels of protein associated
      with TFIID. Transient overexpression of hTAFII105 selectively squelches the
      transcription of some genes in B cells. These properties suggest that TAFII105 is
      a cell type-specific subunit of TFIID that may be responsible for mediating
      transcription by a subset of activators in B cells.

PMID- 8858157
TI  - A unified nomenclature for peroxisome biogenesis factors.

PMID- 8858158
TI  - Protofilaments and rings, two conformations of the tubulin family conserved from
      bacterial FtsZ to alpha/beta and gamma tubulin.

PMID- 8858159
TI  - Localization of HIV-1 RNA in mammalian nuclei.
AB  - The Rev protein of human immunodeficiency virus type 1 (HIV-1) facilitates the
      nuclear export of unspliced and partially spliced viral RNAs. In the absence of
      Rev, these intron-containing HIV-1 RNAs are retained in the nucleus. The basis
      for nuclear retention is unclear and is an important aspect of Rev regulation.
      Here we use in situ hybridization and digital imaging microscopy to examine the
      intranuclear distributions of intron-containing HIV RNAs and to determine their
      spatial relationships to intranuclear structures. HeLa cells were transfected
      with an HIV-1 expression vector, and viral transcripts were localized using
      oligonucleotide probes specific for the unspliced or spliced forms of a
      particular viral RNA. In the absence of Rev, the unspliced viral RNAs were
      predominantly nuclear and had two distinct distributions. First, a population of
      viral transcripts was distributed as approximately 10-20 intranuclear punctate
      signals. Actinomycin D chase experiments indicate that these signals represent
      nascent transcripts. A second, stable population of viral transcripts was
      dispersed throughout the nucleoplasm excluding nucleoli. Rev promoted the export
      of this stable population of viral RNAs to the cytoplasm in a time-dependent
      fashion. Significantly, the distributions of neither the nascent nor the stable
      populations of viral RNAs coincided with intranuclear speckles in which splicing
      factors are enriched. Using splice-junction-specific probes, splicing of human
      beta-globin pre-mRNA occurred cotranscriptionally, whereas splicing of HIV-1 pre
      mRNA did not. Taken together, our results indicate that the nucleolus and
      intranuclear speckles are not involved in Rev regulation, and provide further
      evidence that efficient splicing signals are critical for cotranscriptional
      splicing.

PMID- 8858160
TI  - The organization of endoplasmic reticulum export complexes.
AB  - Export of cargo from the ER occurs through the formation of 60-70nm COPII-coated
      vesicular carriers. We have applied serial-thin sectioning and stereology to
      quantitatively characterize the three-dimensional organization of ER export sites
      in vivo and in vitro. We find that ER buds in vivo are nonrandomly distributed,
      being concentrated in regional foci we refer to as export complexes. The basic
      organization of an export complex can be divided into an active COPII-containing
      budding zone on a single ER cisterna, which is adjacent to budding zones found on
      distantly connected ER cisternae. These budding foci surround and face a central
      cluster of morphologically independent vesicular-tubular elements that contain
      COPI coats involved in retrograde transport. Vesicles within these export
      complexes contain concentrated cargo molecules. The structure of vesicular
      tubular clusters in export complexes is particularly striking in replicas
      generated using a quick-freeze, deep-etch approach to visualize for the first
      time their three-dimensional organization and cargo composition. We conclude that
      budding from the ER through recruitment of COPII is confined to highly
      specialized export complexes that topologically restrict anterograde transport to
      regional foci to facilitate efficient coupling to retrograde recycling by COPI.

PMID- 8858161
TI  - Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane
      association: possible involvement of phosphatidylinositol turnover and Rho
      dependent signaling pathway.
AB  - The ERM proteins, ezrin, radixin, and moesin, are involved in the actin
      filament/plasma membrane interaction as cross-linkers. CD44 has been identified
      as one of the major membrane binding partners for ERM proteins. To examine the
      CD44/ERM protein interaction in vitro, we produced mouse ezrin, radixin, moesin,
      and the glutathione-S-transferase (GST)/CD44 cytoplasmic domain fusion protein
      (GST-CD44cyt) by means of recombinant baculovirus infection, and constructed an
      in vitro assay for the binding between ERM proteins and the cytoplasmic domain of
      CD44. In this system, ERM proteins bound to GST-CD44cyt with high affinity (Kd of
      moesin was 9.3 +/- 1.6nM) at a low ionic strength, but with low affinity at a
      physiological ionic strength. However, in the presence of phosphoinositides
      (phosphatidylinositol [PI], phosphatidylinositol 4-monophosphate [4-PIP], and
      phosphatidylinositol 4.5-bisphosphate [4,5-PIP2]), ERM proteins bound with a
      relatively high affinity to GST-CD44cyt even at a physiological ionic strength:
      4,5-PIP2 showed a marked effect (Kd of moesin in the presence of 4,5-PIP2 was 9.3
      +/- 4.8 nM). Next, to examine the regulation mechanism of CD44/ERM interaction in
      vivo, we reexamined the immunoprecipitated CD44/ERM complex from BHK cells and
      found that it contains Rho-GDP dissociation inhibitor (GDI), a regulator of Rho
      GTPase. We then evaluated the involvement of Rho in the regulation of the
      CD44/ERM complex formation. When recombinant ERM proteins were added and
      incubated with lysates of cultured BHK cells followed by centrifugation, a
      portion of the recombinant ERM proteins was recovered in the insoluble fraction.
      This binding was enhanced by GTP gamma S and markedly suppressed by C3 toxin, a
      specific inhibitor of Rho, indicating that the GTP form of Rho in the lysate is
      required for this binding. A mAb specific for the cytoplasmic domain of CD44 also
      markedly suppressed this binding, identifying most of the binding partners for
      exogenous ERM proteins in the insoluble fraction as CD44. Consistent with this
      binding analysis, in living BHK cells treated with C3 toxin, most insoluble ERM
      proteins moved to soluble compartments in the cytoplasm, leaving CD44 free from
      ERM. These findings indicate that Rho regulates the CD44/ERM complex formation in
      vivo and that the phosphatidylinositol turnover may be involved in this
      regulation mechanism.

PMID- 8858162
TI  - Architecture of coatomer: molecular characterization of delta-COP and protein
      interactions within the complex.
AB  - Coatomer is a cytosolic protein complex that forms the coat of COP I-coated
      transport vesicles. In our attempt to analyze the physical and functional
      interactions between its seven subunits (coat proteins, [COPs] alpha-zeta), we
      engaged in a program to clone and characterize the individual coatomer subunits.
      We have now cloned, sequenced, and overexpressed bovine alpha-COP, the 135-kD
      subunit of coatomer as well as delta-COP, the 57-kD subunit and have identified a
      yeast homolog of delta-COP by cDNA sequence comparison and by NH2-terminal
      peptide sequencing. delta-COP shows homologies to subunits of the clathrin
      adaptor complexes AP1 and AP2. We show that in Golgi-enriched membrane fractions,
      the protein is predominantly found in COP I-coated transport vesicles and in the
      budding regions of the Golgi membranes. A knock-out of the delta-COP gene in
      yeast is lethal. Immunoprecipitation, as well as analysis exploiting the two
      hybrid system in a complete COP screen, showed physical interactions between
      alpha- and epsilon-COPs and between beta- and delta-COPs. Moreover, the two
      hybrid system indicates interactions between gamma- and zeta-COPs as well as
      between alpha- and beta' COPs. We propose that these interactions reflect in vivo
      associations of those subunits and thus play a functional role in the assembly of
      coatomer and/or serve to maintain the molecular architecture of the complex.

PMID- 8858163
TI  - Dilation of the influenza hemagglutinin fusion pore revealed by the kinetics of
      individual cell-cell fusion events.
AB  - We have monitored kinetics of fusion between cell pairs consisting of a single
      influenza hemaglutinin (HA)-expressing cell and a single erythrocyte (RBC) that
      had been labeled with both a fluorescent lipid (Dil) in the membrane and a
      fluorescent solute (calcein) in the aqueous space. Initial fusion pore opening
      between the RBC and HA-expressing cell produced a change in RBC membrane
      potential (delta psi) that was monitored by a decrease in Dil fluorescence. This
      event was followed by two distinct stages of fusion pore dilation: the flux of
      fluorescent lipid (phi L) and the flux of a large aqueous fluorescent dye (phi
      s). We have analyzed the kinetics of events that occur as a result of transitions
      between a fusion pore (FP) and a solute permissive fusion pore (FPs). Our data
      are consistent with a fusion pore comprising six HA trimers.

PMID- 8858164
TI  - Truncation of the COOH-terminal region of the paramyxovirus SV5 fusion protein
      leads to hemifusion but not complete fusion.
AB  - The role of the simian virus 5 (SV5) fusion (F) protein 20 residue COOH-terminal
      region, thought to represent the cytoplasmic tail, in fusion activity was
      examined by constructing a series of COOH-terminal truncation mutants. When the
      altered F proteins were expressed in eukaryotic cells, by using the vaccinia
      virus-T7 transient expression system, all the F proteins exhibited similar
      intracellular transport properties and all were expressed abundantly on the cell
      surface. Quantitative and qualitative cell fusion assays indicated that all of
      the F protein COOH-terminal truncation mutants mediated lipid mixing with similar
      kinetics and efficiency as that of wild-type F protein. However, the cytoplasmic
      content mixing activity decreased in parallel with the extent of the deletion in
      the F protein COOH-terminal truncation mutants. These data indicate that it is
      possible to separate the presumptive early step in the fusion reaction,
      hemifusion, and the final stage of fusion, content mixing, and that the presence
      of the F protein COOH-terminal region is important for the final steps of fusion.

PMID- 8858165
TI  - Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the
      predominantly cytoplasmic PTs1 receptor.
AB  - Import of newly synthesized PTS1 proteins into the peroxisome requires the PTS1
      receptor (Pex5p), a predominantly cytoplasmic protein that cycles between the
      cytoplasm and peroxisome. We have identified Pex13p, a novel integral peroxisomal
      membrane from both yeast and humans that binds the PTS1 receptor via a
      cytoplasmically oriented SH3 domain. Although only a small amount of Pex5p is
      bound to peroxisomes at steady state (< 5%), loss of Pex13p further reduces the
      amount of peroxisome-associated Pex5p by approximately 40-fold. Furthermore, loss
      of Pex13p eliminates import of peroxisomal matrix proteins that contain either
      the type-1 or type-2 peroxisomal targeting signal but does not affect targeting
      and insertion of integral peroxisomal membrane proteins. We conclude that Pex13p
      functions as a docking factor for the predominantly cytoplasmic PTS1 receptor.

PMID- 8858166
TI  - The SH3 domain of the Saccharomyces cerevisiae peroxisomal membrane protein
      Pex13p functions as a docking site for Pex5p, a mobile receptor for the import
      PTS1-containing proteins.
AB  - We identified a Saccharomyces cerevisiae peroxisomal membrane protein, Pex13p,
      that is essential for protein import. A point mutation in the COOH-terminal Src
      homology 3 (SH3) domain of Pex13p inactivated the protein but did not affect its
      membrane targeting. A two-hybrid screen with the SH3 domain of Pex13p identified
      Pex5p, a receptor for proteins with a type I peroxisomal targeting signal (PTS1),
      as its ligand. Pex13p SH3 interacted specifically with Pex5p in vitro. We
      determined, furthermore, that Pex5p was mainly present in the cytosol and only a
      small fraction was associated with peroxisomes. We therefore propose that Pex13p
      is a component of the peroxisomal protein import machinery onto which the mobile
      Pex5p receptor docks for the delivery of the selected PTS1 protein.

PMID- 8858167
TI  - Identification of Pex13p a peroxisomal membrane receptor for the PTS1 recognition
      factor.
AB  - We have identified an S. cerevisiae integral peroxisomal membrane protein of M of
      42,705 (Pex13p) that is a component of the peroxisomal protein import apparatus.
      Pex13p's most striking feature is an src homology 3 (SH3) domain that interacts
      directly with yeast Pex5p (former Pas10p), the recognition factor for the COOH
      terminal tripeptide signal sequence (PTS1), but not with Pex7p (former Pas7p),
      the recognition factor for the NH2-terminal nonapeptide signal (PTS2) of
      peroxisomal matrix proteins. Hence, Pex13p serves as peroxisomal membrane
      receptor for at least one of the two peroxisomal signal recognition factors.
      Cells deficient in Pex13p are unable to import peroxisomal matrix proteins
      containing PTS1 and, surprisingly, also those containing PTS2. Pex13p deficient
      cells retain membranes containing the peroxisomal membrane protein Pex11p (former
      Pmp27p), consistent with the existence of independent pathways for the
      integration of peroxisomal membrane proteins and for the translocation of
      peroxisomal matrix proteins.

PMID- 8858168
TI  - Redox-sensitive homodimerization of Pex11p: a proposed mechanism to regulate
      peroxisomal division.
AB  - Pex11p (formerly Pmp27) has been implicated in peroxisomal proliferation
      (Erdmann, R., and G. Blobel. 1995. J. Cell Biol. 128; 509-523; Marshall, P.A.,
      Y.I. Krimkevich, R.H. Lark, J.M. Dyer, M. Veenhuis, and J.M. Goodman, 1995. J.
      Cell Biol. 129; 345-355). In its absence, peroxisomes in Saccharomyces cerevisiae
      fail to proliferate in response to oleic acid; instead, one or two large
      peroxisomes are formed. Conversely, overproduction of Pex11p causes an increase
      in peroxisomal number. In this report, we confirm the function of Pex11p in
      organelle proliferation by demonstrating that this protein can cause
      fragmentation in vivo of large peroxisomes into smaller organelles. Pex11p is on
      the inner surface of the peroxisomal membrane. It can form homodimers, and this
      species is more abundant in mature peroxisomes than in proliferating organelles.
      Removing one of the three cysteines in the protein inhibits homodimerization.
      This cysteine 3-->alanine mutation leads to an increase in number and a decrease
      in peroxisomal density, compared with the wild-type protein, in response to oleic
      acid. We propose that the active species is the "monomeric" form, and that the
      increasing oxidative metabolism within maturing peroxisomes causes dimer
      formation and inhibition of further organelle division.

PMID- 8858169
TI  - Apical and basolateral endosomes of MDCK cells are interconnected and contain a
      polarized sorting mechanism.
AB  - We have evaluated transcytotic routes in MDCK cells for their ability to generate
      a polarized surface distribution of trafficking proteins by following the
      intracellular sorting of transferrin receptors (TRs). We find that the selective
      basolateral expression of TRs is maintained in the face of extensive trafficking
      between the apical and basolateral surfaces. Biochemical studies of receptors
      loaded with tracer under conditions approaching steady state indicate that TRs
      internalized from the two surfaces are extensively colocalized within MDCK cells
      and that both populations of receptors are selectively delivered to the
      basolateral surface. Tailless TRs in which the cytoplasmic domain has been
      deleted display an unpolarized cell surface distribution and recycle in an
      unpolarized fashion. We show by EM that wild-type receptors internalized from
      each surface are colocalized within endosomal elements distributed throughout the
      cytoplasm. By preloading endosomal elements directly accessible from the
      basolateral surface with transferrin (Tf)-HRP, we show that apically internalized
      TRs rapidly enter the same compartment. We also show that both transcytosing
      (apically internalized) and recycling (basolaterally internalized) TRs are
      delivered to the basolateral border by a distinctive subset of exocytotic, 60-nm
      diam vesicles. Together, the biochemical and morphological data show that apical
      and basolateral endosomes of MDCK cells are interconnected and contain a signal
      dependent polarized sorting mechanism. We propose a dynamic model of polarized
      sorting in MDCK cells in which a single endosome-based, signal-dependent sorting
      step is sufficient to maintain the polarized phenotype.

PMID- 8858170
TI  - Rab8 promotes polarized membrane transport through reorganization of actin and
      microtubules in fibroblasts.
AB  - Rab8 is a small Ras-like GTPase that regulates polarized membrane transport to
      the basolateral membrane in epithelial cells and to the dendrites in neurons. It
      has recently been demonstrated that fibroblasts sort newly synthesized proteins
      into two different pathways for delivery to the cell surface that are equivalent
      to the apical and the basolateral post-Golgi routes in epithelial cells
      (Yoshimori, T., P. Keller, M.G. Roth, and K. Simons. 1996. J. Cell Biol. 133:247
      256). To determine the role of Rab8 in fibroblasts, we used both transient
      expression systems and stable cell lines expressing mutant or wild-type (wt)
      Rab8. A dramatic change in cell morphology occurred in BHK cells expressing both
      the wt Rab8 and the activated form of the GTPase, the Rab8Q67L mutant. These
      cells formed processes as a result of a reorganization of both their actin
      filaments and microtubules. Newly synthesized vesicular stomatitis virus G
      glycoprotein, a basolateral marker protein in MDCK cells, was preferentially
      delivered into these cell outgrowths. Based on these findings, we propose that
      Rab8 provides a link between the machinery responsible for the formation of cell
      protrusions and polarized biosynthetic membrane traffic.

PMID- 8858171
TI  - Dynamics of capping protein and actin assembly in vitro: uncapping barbed ends by
      polyphosphoinositides.
AB  - Bursts of actin polymerization in vivo involve the transient appearance of free
      barbed ends. To determine how rapidly barbed ends might appear and how long they
      might remain free in vivo, we studied the kinetics of capping protein, the major
      barbed end capper, binding to barbed ends in vitro. First, the off-rate constant
      for capping protein leaving a barbed end is slow, predicting a half-life for a
      capped barbed end of approximately 30 min. This half-life implies that cells
      cannot wait for capping protein to spontaneously dissociate from capped barbed
      ends in order to create free barbed ends. However, we find that
      phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-mono
      phosphate (PIP) cause rapid and efficient dissociation of capping protein from
      capped filaments. PIP2 is a strong candidate for a second messenger regulating
      actin polymerization; therefore, the ability of PIP2 to remove capping protein
      from barbed ends is a potential mechanism for stimulating actin polymerization in
      vivo. Second, the on-rate constant for capping protein binding to free barbed
      ends predicts that actin filaments could grow to the length of filaments observed
      in vivo during one lifetime. Third, capping protein beta-subunit isoforms did not
      differ in their actin binding properties, even in tests with different actin
      isoforms. A major hypothesis for why capping protein beta-subunit isoforms exist
      is thereby excluded. Fourth, the proposed capping protein regulators, Hsc70 and
      S100, had no effect on capping protein binding to actin in vitro.

PMID- 8858172
TI  - Calcium waves along the cleavage furrows in cleavage-stage Xenopus embryos and
      its inhibition by heparin.
AB  - Calcium signaling is known to be associated with cytokinesis; however, the
      detailed spatio-temporal pattern of calcium dynamics has remained unclear. We
      have studied changes of intracellular free calcium in cleavage-stage Xenopus
      embryos using fluorescent calcium indicator dyes, mainly Calcium Green-1.
      Cleavage formation was followed by calcium transients that localized to cleavage
      furrows and propagated along the furrows as calcium waves. The calcium transients
      at the cleavage furrows were observed at each cleavage furrow at least until
      blastula stage. The velocity of the calcium waves at the first cleavage furrow
      was approximately 3 microns/s, which was much slower than that associated with
      fertilization/egg activation. These calcium waves traveled only along the
      cleavage furrows and not in the direction orthogonal to the furrows. These
      observations imply that there exists an intracellular calcium-releasing activity
      specifically associated with cleavage furrows. The calcium waves occurred in the
      absence of extracellular calcium and were inhibited in embryos injected with
      heparin an inositol 1,4,5-trisphosphate (InsP3) receptor antagonist. These
      results suggest that InsP3 receptor-mediated calcium mobilization plays an
      essential role in calcium wave formation at the cleavage furrows.

PMID- 8858173
TI  - Local perinuclear calcium signals associated with mitosis-entry in early sea
      urchin embryos.
AB  - Using calcium-sensitive dyes together with their dextran conjugates and confocal
      microscopy, we have looked for evidence of localized calcium signaling in the
      region of the nucleus before entry into mitosis, using the sea urchin egg first
      mitotic cell cycle as a model. Global calcium transients that appear to originate
      from the nuclear area are often observed just before nuclear envelope breakdown
      (NEB). In the absence of global increases in calcium, confocal microscopy using
      Calcium Green-1 dextran indicator dye revealed localized calcium transients in
      the perinuclear region. We have also used a photoinactivatable calcium chelator,
      nitrophenyl EGTA (NP-EGTA), to test whether the chelator-induced block of mitosis
      entry can be reversed after inactivation of the chelator. Cells arrested before
      NEB by injection of NP-EGTA resume the cell cycle after flash photolysis of the
      chelator. Photolysis of chelator triggers calcium release. TreatmenT with
      caFfeine to enhance calcium-induced calcium release increases the amplitude of
      NEB-associated calcium transients. These results indicate that calcium increases
      local to the nucleus are required to trigger entry into mitosis. Local calcium
      transients arise in the perinuclear region and can spread from this region into
      the cytoplasm. Thus, cell cycle calcium signals are generated by the perinuclear
      mitotic machinery in early sea urchin embryos.

PMID- 8858174
TI  - Microtubule dynamics at the G2/M transition: abrupt breakdown of cytoplasmic
      microtubules at nuclear envelope breakdown and implications for spindle
      morphogenesis.
AB  - We recently developed a direct fluorescence ratio assay (Zhai, Y., and G.G.
      Borisy. 1994. J. Cell Sci. 107:881-890) to quantify microtubule (MT) polymer in
      order to determine if net MT depolymerization occurred upon anaphase onset as the
      spindle was disassembled. Our results showed no net decrease in polymer,
      indicating that the disassembly of kinetochore MTs was balanced by assembly of
      midbody and astral MTs. Thus, the mitosis-interphase transition occurs by a
      redistribution of tubulin among different classes of MTs at essentially constant
      polymer level. We now examine the reverse process, the interphase-mitosis
      transition. Specifically, we quantitated both the level of MT polymer and the
      dynamics of MTs during the G2/M transition using the fluorescence ratio assay and
      a fluorescence photoactivation approach, respectively. Prophase cells before
      nuclear envelope breakdown (NEB) had high levels of MT polymer (62%) similar to
      that previously reported for random interphase populations (68%). However,
      prophase cells just after NEB had significantly reduced levels (23%) which
      recovered as MT attachments to chromosomes were made (prometaphase, 47%;
      metaphase, 56%). The abrupt reorganization of MTs at NEB was corroborated by anti
      tubulin immunofluorescence staining using a variety of fixation protocols.
      Sensitivity to nocodazole also increased at NEB. Photoactivation analyses of MT
      dynamics showed a similar abrupt change at NEB, basal rates of MT turnover (pre
      NEB) increased post-NEB and then became slower later in mitosis. Our results
      indicate that the interphase-mitosis (G2/M) transition of the MT array does not
      occur by a simple redistribution of tubulin at constant polymer level as the
      mitosis-interphase (M/G1) transition. Rather, an abrupt decrease in MT polymer
      level and increase in MT dynamics occurs tightly correlated with NEB. A
      subsequent increase in MT polymer level and decrease in MT dynamics occurs
      correlated with chromosome attachment. These results carry implications for
      understanding spindle morphogenesis. They indicate that changes in MT dynamics
      may cause the steady-state MT polymer level in mitotic cells to be lower than in
      interphase. We propose that tension exerted on the kMTs may lead to their
      lengthening and thereby lead to an increase in the MT polymer level as
      chromosomes attach to the spindle.

PMID- 8858175
TI  - Targeted mutation of plakoglobin in mice reveals essential functions of
      desmosomes in the embryonic heart.
AB  - Plakoglobin (gamma-catenin), a member of the armadillo family of proteins, is a
      constituent of the cytoplasmic plaque of desmosomes as well as of other adhering
      cell junctions, and is involved in anchorage of cytoskeletal filaments to
      specific cadherins. We have generated a null mutation of the plakoglobin gene in
      mice. Homozygous -/- mutant animals die between days 12-16 of embryogenesis due
      to defects in heart function. Often, heart ventricles burst and blood floods the
      pericard. This tissue instability correlates with the absence of desmosomes in
      heart, but not in epithelia organs. Instead, extended adherens junctions are
      formed in the heart, which contain desmosomal proteins, i.e., desmoplakin. Thus,
      plakoglobin is an essential component of myocardiac desmosomes and seems to play
      a crucial role in the sorting out of desmosomal and adherens junction components,
      and consequently in the architecture of intercalated discs and the stabilization
      of heart tissue.

PMID- 8858176
TI  - Overexpression of bone morphogenetic protein-6 (BMP-6) in the epidermis of
      transgenic mice: inhibition or stimulation of proliferation depending on the
      pattern of transgene expression and formation of psoriatic lesions.
AB  - Bone morphogenetic protein-6 (BMP-6) belongs to the family of TGF-beta-related
      growth factors. In the developing epidermis, expression of BMP-6 coincides with
      the onset of stratification. Expression persists perinatally but declines after
      day 6 postpartum, although it can still be detected in adult skin by reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis. We constitutively
      overexpressed BMP-6 in suprabasal layers of interfollicular epidermis in
      transgenic mice using a keratin 10 promoter. All mice expressing the transgene
      developed abnormalities in the skin, indicating an active transgene-derived
      factor. Depending on the pattern of transgene expression, the effects on
      proliferation and differentiation were completely opposite. Strong and uniform
      expression of the BMP-6 transgene resulted in severe repression of cell
      proliferation in embryonic and perinatal epidermis but had marginal effects on
      differentiation. Weaker and patchy expression of the transgene evoked strong
      hyperproliferation and parakeratosis in adult epidermis and severe perturbations
      of the usual pattern of differentiation. These perturbations included changes in
      the expression of keratins and integrins. Together with an inflammatory
      infiltrate both in the dermis and in the epidermis, these aspects present all
      typical histological and biochemical hallmarks of a human skin disease:
      psoriasis.

PMID- 8858177
TI  - Altered secondary myogenesis in transgenic animals expressing the neural cell
      adhesion molecule under the control of a skeletal muscle alpha-actin promoter.
AB  - The majority of skeletal muscle fibers are generated through the process of
      secondary myogenesis. Cell adhesion molecules such as NCAM are thought to be
      intricately involved in the cell-cell interactions between developing secondary
      and primary myotubes. During secondary myogenesis, the expression of NCAM in
      skeletal muscle is under strict spatial and temporal control. To investigate the
      role of NCAM in the regulation of primary-secondary myotube interactions and
      muscle fusion in vivo, we have examined muscle development in transgenic mice
      expressing the 125-kD muscle-specific, glycosylphosphatidylinositol-anchored
      isoform of human NCAM, under the control of a human skeletal muscle alpha-actin
      promoter that is active from about embryonic day 15 onward. Analysis of
      developing muscle from transgenic animals revealed a significantly lower number
      of myofibers encased by basal lamina at postnatal day 1 compared with
      nontransgenic littermates, although the total number of developing myofibers was
      similar. An increase in muscle fiber size and decreased numbers of VCAM-1
      positive secondary myoblasts at postnatal day 1 was also found, indicating
      enhanced secondary myoblast fusion in the transgenic animals. There was also a
      significant decrease in myofiber number but no increase in overall muscle size in
      adult transgenic animals; other measurements such as the number of nuclei per
      fiber and the size of individual muscle fibers were significantly increased,
      again suggesting increased secondary myoblast fusion. Thus the level of NCAM in
      the sarcolemma is a key regulator of cell-cell interactions occurring during
      secondary myogenesis in vivo and fulfills the prediction derived from
      transfection studies in vitro that the 125-kD NCAM isoform can enhance myoblast
      fusion.

PMID- 8858178
TI  - Intracellular signaling is changed after clustering of the neural cell adhesion
      molecules axonin-1 and NgCAM during neurite fasciculation.
AB  - Neural cell adhesion molecules of the immunoglobulin/fibronectin type III family
      on axons have been implicated in promotion of neurite outgrowth, fasciculation,
      and the mediation of specific cell adhesion. The present study demonstrates that
      two of these molecules on dorsal root ganglion neurons are associated with
      distinct protein kinases, axonin-1 with the src-related nonreceptor tyrosine
      kinase fyn and NgCAM with a casein kinase II-related activity and a serine/
      threonine kinase related to S6 kinase. When neurites grew without contacts
      involving axonin-1 and NgCAM, strong fyn kinase activity was associated with
      axonin-1, whereas the NgCAM-associated kinase activities were low. Clustering of
      axonin-1 with NgCAM induced by the formation of cell-cell contacts correlated
      with a reduction of the axonin-1-associated fyn activity and an increased
      phosphorylation of NgCAM by the associated casein kinase II-related activity.
      Thus, axonin-1 and NgCAM trigger distinctive intracellular signals during in
      vitro differentiation depending on their state of association.

PMID- 8858179
TI  - A developmental defect in Plasmodium falciparum male gametogenesis.
AB  - Asexually replicating populations of Plasmodium parasites, including those from
      cloned lines, generate both male and female gametes to complete the malaria life
      cycle through the mosquito. The generation of these sexual forms begins with the
      induction of gametocytes from haploid asexual stage parasites in the blood of the
      vertebrate host. The molecular processes that govern the differentiation and
      development of the sexual forms are largely unknown. Here we describe a defect
      that affects the development of competent male gametocytes from a mutant clone of
      P. falciparum (Dd2). Comparison of the Dd2 clone to the predecessor clone from
      which it was derived (W2'82) shows that the defect is a mutation that arose
      during the long-term cultivation of asexual stages in vitro. Light and electron
      microscopic images, and indirect immunofluorescence assays with male-specific
      anti-alpha-tubulin II antibodies, indicate a global disruption of male
      development at the gametocyte level with at least a 70-90% reduction in the
      proportion of mature male gametocytes by the Dd2 clone relative to W2'82. A high
      prevalence of abnormal gametocyte forms, frequently containing multiple and
      unusually large vacuoles, is associated with the defect. The reduced production
      of mature male gametocytes may reflect a problem in processes that commit a
      gametocyte to male development or a progressive attrition of viable male
      gametocytes during maturation. The defect is genetically linked to an almost
      complete absence of male gamete production and of infectivity to mosquitoes. This
      is the first sex-specific developmental mutation identified and characterized in
      Plasmodium.

PMID- 8858181
TI  - Presenile because of presenilin: the presenilin genes and early onset Alzheimer's
      disease.
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by the massive
      and invariant accumulation of amyloid plaques in the brains of affected patients.
      In many cases Alzheimer's disease occurs in the absence of a prior history of the
      disease in other family members and is designated as sporadic, whereas in
      approximately 10% of patients, dominantly transmitted mutations within one of
      three genes are found. A few mutations have been identified within the gene
      encoding the beta-amyloid precursor protein; however, these mutations account for
      only about 1-3% of cases with familial Alzheimer's disease. In the majority of
      autosomal dominant cases (40-50%), mutations have been found in a gene localized
      to chromosome 14. The responsible gene, now called presenilin-1, has recently
      been identified and shown to encode a putative seven transmembrane domain
      protein. Surprisingly, a second highly homologous gene (named presenilin-2) was
      cloned shortly thereafter. It is localized on human chromosome 1 and is also
      involved in a small number of cases with familial Alzheimer's disease. Early data
      suggest that mutations found within the two genes cause early onset Alzheimer's
      disease by influencing the proteolytic processing of amyloid beta-peptide in a
      pathological manner.

PMID- 8858180
TI  - Mast cells that reside at different locations in the jejunum of mice infected
      with Trichinella spiralis exhibit sequential changes in their granule
      ultrastructure and chymase phenotype.
AB  - Whether or not a nontransformed, mature mouse mast cell (MC) or its committed
      progenitor can change its granule protease phenotype during inflammatory
      responses, has not been determined. To address this issue, the granule morphology
      and protease content of the MC in the jejunum of BALB/c mice exposed to
      Trichinella spiralis were assessed during the course of the infection. Within 1
      wk after helminth infection of the mice, increased numbers of MC appeared in the
      crypts at the base of the villi, and by wk 2 the number of MC throughout the
      villi increased by approximately 25-fold. Shortly after the peak of the
      mastocytosis, the intraepithelial population of MC disappeared, followed by a
      progressive loss of lamina propria MC. The presence of stellate-shaped granules
      containing crystalline structures in intraepithelial MC at the height of
      infection and the retention of such granules with fragmented crystals in lamina
      propria MC during resolution of the mastocytosis suggest that MC migrate during
      the various phases of the inflammation. As assessed by immunohistochemical
      analyses of serial sections, predominant chymase phenotypes were observed at the
      height of the infection in the muscle that expressed mouse MC protease (mMCP) 5
      without mMCP-1 or mMCP-2 and in the epithelium that expressed mMCP-1 and mMCP-2
      without mMCP-5. Accompanying these two MC populations were transitional forms in
      the submucosa that expressed mMCP-2 and mMCP-5 without mMCP-1 and in the lamina
      propria that expressed mMCP-2 alone. These data suggest that jejunal MC
      sequentially express mMCP-2, cease expressing mMCP-5, and finally express mMCP-1
      as the cells progressively appear in the submucosa, lamina propria, and
      epithelium, respectively. In the recovery phase of the disease, MC sequentially
      cease expressing mMCP-1, express mMCP-5, and finally cease expressing mMCP-2 as
      they present at the tips of the villi, the base of the villi, and the submucosa,
      respectively. That MC can reversibly alter their protease phenotypes suggests
      that a static nomenclature with fixed functional implications is inadequate to
      describe MC populations during an inflammatory process within a particular
      tissue.

PMID- 8858182
TI  - Oxidative stress and mitochondrial dysfunction in neurodegeneration.
AB  - Rapid advances are being made in our understanding of the pathogenesis of
      neurodegenerative diseases, particularly those in which specific DNA mutations
      have been identified. beta-amyloid has been shown to induce free radical
      formation both directly and via an effect on endothelial function. There is
      presuasive evidence for cytochrome oxidase dysfunction with oxidative stress and
      damage in the brains of patients with Alzheimer's disease. The confirmation of
      the complex II inhibitor 3-nitropropionic acid as a toxin model for Huntington's
      disease, together with the demonstration of reduced mitochondrial function in
      Huntington's disease caudate, supports the proposition that mutant huntingtin may
      exert its effect through an abnormality of energy metabolism.

PMID- 8858183
TI  - Apolipoprotein E in neurology.
AB  - Apolipoprotein E became relevant for neurologists in 1993 when the association of
      the apolipoprotein E-epsilon 4 allele with familial and sporadic late-onset
      Alzheimer disease was reported. Since that time, more than 100 confirmations and
      many research papers have appeared. A large neurobiological literature concerning
      the role of apolipoprotein E in the metabolism of the central nervous system is
      developing.

PMID- 8858184
TI  - Dementia with Lewy bodies.
AB  - Dementia with Lewy bodies is a generic term which was proposed at the first
      International Workshop on Lewy Body Dementia (Newcastle upon Tyne, 1995). It is
      an all encompassing term that includes various types of disorder such as diffuse
      Lewy body disease, senile dementia of Lewy body type, and Lewy body variant of
      Alzheimer's disease. Epidemiological, clinical, neuropathological, biochemical,
      molecular biological, and therapeutic contributions to the understanding of
      dementia with Lewy bodies are reviewed.

PMID- 8858185
TI  - Asymmetric cortical degeneration syndromes.
AB  - Asymmetric cortical degeneration syndromes (aphasic, perceptual-motor, frontal
      lobe and bitemporal categories) encompass the majority of atypical cortical
      dementia patterns. New insights suggest the group is genetically heterogeneous.
      Debate continues over whether individual syndromes are points along a continuum
      or distinct nosologic entities.

PMID- 8858186
TI  - Spectrum of memory dysfunction in degenerative disease.
AB  - We have summarized relevant literature on the patterns of memory deficit found in
      Alzheimer's disease, the focal lobar atrophies (semantic dementia and dementia of
      frontal type) and three forms of subcortical dementia (progressive supranuclear
      palsy, Huntington's and Parkinson's disease). We have stressed an approach based
      on the joint principals of cognitive neuropsychology and applied neuroanatomy.
      Alzheimer's disease results in a severe deficit in the establishment of new
      episodic memories which reflects the perihippocampal locus of the early
      pathology. In semantic dementia, there is profound progressive and relatively
      pure loss of semantic memory associated with focal left temporal neocortical
      atrophy. By contrast, in the subcortical dementias the major impairments are in
      working (immediate) memory and retrieval of information from longer term memory
      stores, deficits which reflect dysfunction of frontostriatal systems.

PMID- 8858187
TI  - Genetics of movement disorders.
AB  - Trinucleotide repeat expansions or unstable mutations are the cause of a growing
      number of hereditary movement disorders, especially inherited ataxias. Diagnostic
      practice as well as disease classifications have altered accordingly. Genes
      responsible for "Parkinsonian plus' syndromes and episodic movement disorders
      have also been recently mapped.

PMID- 8858188
TI  - Chorea.
AB  - The Huntington's disease mutation and its protein product are widely expressed in
      the brain, although the link to presumed excitotoxic damage is unknown. The
      availability of the genetic test increased the study of preclinical changes in
      the disease and the identification of more rare choreic illnesses. Other types of
      transient or permanent basal ganglia dysfunction might cause chorea.

PMID- 8858189
TI  - Parkinson's disease: biology and aetiology.
AB  - The cause of dopamine cell death, thought to be the primary neurocytologic defect
      in idiopathic Parkinson's disease, remains unknown. Mitochondrial oxidative
      dysfunction causes premature cell death, and may be linked to accelerated
      apoptosis, excessive free and toxic radicals, deficient neurotrophic factors or
      combinations of these detrimental factors. Neurochemical imbalances result both
      in the substantia nigra and neostriatum, resulting in compensatory mechanisms
      that make this chronic neurodegenerative disease difficult to evaluate. Acute
      parkinsonism models have limitations when compared with chronic disease states,
      and caution should be present when comparing 'parkinsonism' data with human
      disease. Better understanding of classical neurotransmitters, neuroactive
      peptides and neurotrophic factors, will hopefully lead to more rational treatment
      approaches, cellular support strategies, and an understanding of the causes of
      this disease. Glial derived neurotrophic factor looks the most promising
      neurotrophic candidate so far tested in culture and in vivo. The result of
      clinical trials utilizing neurotrophic factors, both as mesencephalic implant
      support strategies and as definitive treatment of idiopathic Parkinson's disease,
      are awaited with cautious optimism.

PMID- 8858190
TI  - Controversies in the treatment of Parkinson's disease.
AB  - Although theoretical reasons exist for believing that selegiline slows the
      progression of Parkinson's disease, this has not been shown in clinical trials.
      Selegiline improves the symptoms of Parkinson's disease, allowing the
      introduction of levodopa to be delayed in de-novo patients and, later, for
      levodopa to be used at a lower dose. It does not lessen the long-term problems of
      dyskinesia and fluctuations associated with levodopa therapy. The report of an
      increased mortality associated with selegiline therapy awaits further evaluation.
      Of the dopamine agonists, pergolide appears to be more potent than bromocriptine;
      cabergoline looks promising. The catechol-O-methyltransferase inhibitors,
      tolcapone and entacopone, prolong the duration of action of levodopa and also
      show promise. The main objective in the drug treatment of Parkinson's disease
      remains the optimization of the dose and frequency of levodopa administration.

PMID- 8858191
TI  - Myoclonus.
AB  - Physiological investigations continue to define the processes underlying
      different types of myoclonus, particularly cortical forms. Several new
      aetiologies have been described and genetic advances have revealed the basic
      deficit in familial hyperekplexia.

PMID- 8858192
TI  - Torsion dystonia.
AB  - We review the experimental evidence from genetic and neurophysiological studies
      on idiopathic and secondary torsion dystonias. We also discuss the treatment of
      dystonia by botulinum toxin injections and surgical therapy.

PMID- 8858193
TI  - Non-Parkinson akinetic-rigid syndromes.
AB  - We review developments in the study of akinetic-rigid syndromes other than
      Parkinson's disease within three main categories: recording of new etiologies,
      advancing knowledge on previously known causes, and studies of Parkinson's
      disease imitators and clinical and investigational means of accurately
      distinguishing them from Parkinson's disease.

PMID- 8858194
TI  - Degenerative diseases.

PMID- 8858195
TI  - Movement disorders.

PMID- 8858196
TI  - Evaluation of recurrent respiratory tract infections in children.

PMID- 8858197
TI  - America's families: then and now.

PMID- 8858198
TI  - Functional recovery following head injury among children.

PMID- 8858199
TI  - Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile
      visceral steatosis mice with systemic carnitine deficiency.
AB  - A quantitative study of the effect of carnitine deficiency on expression of
      glycolytic and gluconeogenic enzymes was performed using juvenile visceral
      steatosis mice which are systemically deficient in carnitine. The amounts of
      glucokinase and L-type pyruvate kinase mRNA were reduced in homozygotes, compared
      to heterozygotes and normal controls at 2 and 8 weeks. Liver-type
      phosphofructokinase, however, did not differ significantly. The abundance of
      fructose 1,6-bisphosphatase mRNA was unchanged at 2 and 8 weeks. The level of
      phosphoenolpyruvate carboxykinase mRNA was increased slightly at 2 weeks, but not
      at 8 weeks. A part of these changes could not be explained by the plasma glucose
      or insulin level. Carnitine administration restored the mRNA of these enzymes to
      normal levels. These results suggest that carnitine deficiency affects the
      expression of these liver enzymes.

PMID- 8858200
TI  - Rectification of diabetic state in C57BL/KsJ-db/db mice by the implantation of
      pancreatic beta cell line MIN6.
AB  - C57BL/KsJ mice carrying homozygous db/db mutation (db/db mice) are characterized
      by extreme obesity and early onset of hyperglycemia. In an attempt to rectify
      diabetes of these mice, a pancreatic beta cell line MIN6, which retains glucose
      inducible insulin secretion, was transplanted subcutaneously into the back of the
      mice. Glucose and insulin levels of individual mice were examined biweekly and
      their weight gain weekly. All mice were sacrificed at 100 days after the
      transplantation of MIN6 cells. In db/db mice that had received MIN6 cells, blood
      insulin levels were restored and blood glucose levels were reduced to those of
      non-diabetic mice, although they remained obese. Glucose tolerance test suggested
      that transplanted MIN6 cells responded to loaded glucose as beta cells of non
      diabetic mice. Immunohistochemical study showed that transplanted MIN6 cells
      produced insulin. Fatty liver associated with diabetes mellitus observed in db/db
      mice was not found in the MIN6 cell-transplanted mice. Implication of the results
      is discussed with reference to potential therapies for severe diabetes.

PMID- 8858201
TI  - Failure of nimodipine to prevent or correct the long-term nerve conduction defect
      and increased neuronal Ca(2+)-currents in the diabetic BB/W-rat.
AB  - It has been suggested that L-type Ca2+ channel antagonists exert a beneficial
      effect on nerve conduction velocity (NCV) slowing in short-term experimental
      diabetic neuropathy. We examined the effects of long-term treatment with the L
      channel blocker, nimodipine, on two aspects of neuronal function previously
      documented to be abnormal in the spontaneously diabetic BB/W-rat: nerve
      conduction velocity and calcium influx in dorsal root ganglion (DRG) neurons.
      Treatment with 20 mg/kg nimodipine i.p. every 48 h from onset of diabetes for 6
      months led to a transient, non-significant (30%) improvement in NCV. Intervention
      with the same regimen from 3 to 6 months of diabetes had no corrective effect on
      the already established NCV defect. Voltage activated calcium currents were
      recorded in isolated DRG neurons from nimodipine-treated and untreated diabetic
      and non-diabetic age-matched BB/W control rats. The peak high-threshold calcium
      current density (IDCa, pA/pF) was significantly larger in non-treated diabetic
      rats compared with control rats (157 +/- 12 vs. 66 +/- 5.5 (P < or = 0.05)). Long
      term treatment with nimodipine was associated with a non-significant (28%)
      decrease (112 +/- 29) in the IDCa compared with non-treated diabetic rats. We
      conclude that L-channel mediated perturbations of cytosolic Ca2+ levels are only
      of minor pathophysiologic significance in the development of chronic diabetic
      neuropathy.

PMID- 8858203
TI  - Macular recovery time in diabetic children without retinopathy.
AB  - The aim of this study was to evaluate whether patients with initial diabetic
      nephropathy (defined as persistent microalbuminuria) have an impairment of
      macular recovery time and if this impairment changes in a long-term follow-up.
      Eighty insulin-dependent diabetic children without fluorescein angiographic signs
      of retinopathy and 80 controls were included in the study. All patients underwent
      nyctometry at the beginning of the study; diabetic children repeated the same
      test after 7 years. Diabetics were divided into two subgroups as regards presence
      of persistent microalbuminuria (albumin excretion rate > 20 micrograms/min/1.73
      m2). At the beginning of the study, diabetics as a whole and normoalbuminuric
      patients showed similar data to controls, while microalbuminuric ones showed
      worse data at nyctometry (initial recovery time (IRT): 44.89 +/- 12.50; Summation
      method (SM): 509.1 +/- 312.0) in comparison with normoalbuminuric (IRT: 38.12 +/-
      10.31, P = 0.010; SM 648.6 +/- 272.2, P = 0.036) and control subjects (IRT: 37.77
      +/- 11.82, P = 0.004; SM: 661.5 +/- 297.5, P = 0.013). After 7 years,
      normoalbuminuric subjects showed a slight, but not significant worsening of
      nyctometry, while in microalbuminuric ones a significant difference between
      baseline and the end of follow-up was found (IRT: 44.89 +/- 12.50 vs. 52.91 +/-
      13.9, P < 0.01; SM: 509.1 +/- 312.0 vs. 374.8 +/- 271.9, P < 0.05). Diabetic
      patients had a higher rate of abnormal IRT and SM than controls (P = 0.0004 and P
      = 0.0006, respectively). A higher number of patients in microalbuminuric subgroup
      than in normoalbuminuric one were found (both at baseline and at the end of
      follow-up) above the 95th centile of IRT (baseline 3 vs. 15; P = 0.0002; end of
      follow-up 5 vs. 23; P < 0.0001) and below the 5th centile of SM (baseline 5 vs.
      14; P = 0.004; end of follow-up 5 vs. 19; P < 0.0001). Nyctometry was found more
      altered in microalbuminuric patients than in normoalbuminuric and controls.
      Unfortunately, there is a large overlap between the two diabetic subgroups and
      between diabetics and controls; for this reason, this technique is not suited for
      everyday practice.

PMID- 8858202
TI  - Favourable, significant effect of the dose-dependent treatment with RU 38486 (RU)
      on the alterations of the hepatic mitochondrial function of diabetic rats.
AB  - In the present work, the effect "in vivo' of increasing doses of RU 38486 upon
      the hepatic mitochondrial function of diabetic rats has been studied. At the same
      time, the action of adrenalectomy and corticosterone restitution on this function
      were comparatively demonstrated. The parameters measured were oxygen consumption
      with the substrates: 3-hydroxybutyrate (HB), succinate (Suc) and malate-glutamate
      (Mal-glut) in intact liver mitochondria and the activities of 3-hydroxybutyrate
      dehydrogenase (HBD) and cytochrome c oxidase (Cyt.c oxid.) enzymes in broken
      liver mitochondria. The groups of animals studied were normal controls (N) and
      the following groups of diabetic rats: rats without any treatment (D),
      adrenalectomized rats (D+ADX), rats that were adrenalectomized and treated with
      corticosterone (D+ADX+C) and four groups treated with increasing oral doses of RU
      (in mg/kg body wt.), that is, 12.5 (D+RU1), 25.0 (D+RU2), 37.5 (D+RU3) and 50.0
      (D+RU4). The results showed a tendency of increasing values of mitochondrial
      oxygen consumption in diabetic animals treated with RU. The favourable effect of
      increasing doses of RU on O2 consumption of diabetic rat liver mitochondria with
      each of the substrates showed a significant association as indicated by the
      values obtained for the correlation coefficients r (0.95, 0.97 and 0.99 according
      to the substrate HB, Succ or Mal-glut, respectively). Likewise, the correlation
      between the treatment with increasing doses of RU and the recovery of enzyme
      activities showed a significant dose-effect association with r 0.94 for HBD and r
      = 0.95 for Cyt.c oxid. Adrenalectomy showed a similar effect to treatment with
      the maximum dose of RU while corticosterone restitution gave measured values
      similar to those of the D group. In conclusion, the favourable, significant
      variation of the hepatic mitochondrial function of diabetic rats was demonstrated
      by the dose-dependent treatment with RU as seen by the correlation statistical
      study performed. At the same time, the pernicious effect that glucocorticoids
      exert upon such function in experimental diabetes was confirmed.

PMID- 8858204
TI  - Epidemiology of renal involvement in type II diabetics (NIDDM) in Catalonia. The
      Catalan Diabetic Nephropathy Study Group.
AB  - The aim of this cross-sectional study was to establish the prevalence of renal
      involvement and to identify associations with its most important possible risk
      factors in a group of patients with Type II diabetes mellitus, representative of
      the population living in Catalonia. One thousand two hundred and three patients
      (47% males, mean age: 61 +/- 6 years, diabetes duration 9 +/- 6 years) were
      studied. Overnight urine samples were collected to determine urinary albumin
      excretion (UAE). If UAE was > 15 micrograms/min, a new 24-h urine collection for
      UAE measurement to establish the existence of microalbuminuria (20-200
      micrograms/min) or macroalbuminuria (> 200 micrograms/min) was obtained. Clinic
      and metabolic evaluations were also performed. The prevalence (%) of
      microalbuminuria, macroalbuminuria and hypertension were, respectively, 23. 1,
      5.4 and 42. In comparison with normoalbuminurics, patients with microalbuminuria
      were predominately male (P < 0.03), with a significantly higher systolic (P <
      0.001) and diastolic (P < 0.001) blood pressure and body mass index (P < 0.001).
      The prevalence of smokers (former + current) was higher in patients with
      microalbuminuria (43 vs 32%, P < 0.025). Moreover, patients with nephropathy had
      more prevalence of retinopathy (P < 0.001), neuropathy (P < 0.001), peripheral
      angiopathy (P < 0.001) and coronary disease (P < 0.001). The prevalence of
      microalbuminuria in Type II diabetes in Catalonia is similar to that observed in
      other european countries. The existence of microalbuminuria is associated with
      several diabetic complications, as well as tobacco consumption and obesity.

PMID- 8858205
TI  - Incidence of insulin-dependent diabetes (IDDM) and non-insulin-dependent diabetes
      (NIDDM) (0-34 years at onset) in Benghazi, Libya.
AB  - The incidence of insulin-dependent diabetes (IDDM) and non-insulin-dependent
      diabetes (NIDDM) in Benghazi, Libya in the < 35-year age group during the period
      1981-1990 are reported. Incidence data for IDDM were based on prospective
      registration of patients while incidence data for NIDDM were based on analysis of
      files. Case ascertainment of IDDM cases was estimated to be > 95%. Incidence of
      total diabetes (IDDM and NIDDM) (per 100000 population) was significantly higher
      in females (43.8; 95% confidence Interval (CI) 40.6-47.2) than in males (28.9,
      26.6-31.3) (P < 0.001). The overall incidence rates of IDDM and NIDDM were 9.0
      (CI, 8.1-10.0) and 27.3 (CI, 25.4-28.2), respectively. Rates of IDDM were 9.4
      (CI, 8.1-10.9) among males and 8.5 (CI, 7.3-10.0) among females. Rates of NIDDM
      were 19.6 (CI, 18.1-22.2) among males and 35.3 (CI, 32.4-37.8) among females.
      IDDM patients showed a female predominance in the 0- to 14-year age range (P >
      0.05) and a male predominance in the 15- to 34-year age range (P > 0.05). NIDDM
      showed equal incidence in males and females in the 0- to 14-year age range and
      twofold higher incidence in females than in males in the 15- to 34-year age group
      (P < 0.001). Yearly variation and seasonality of onset were not significant in
      IDDM cases (P > 0.05). Fifty-six percent of NIDDM cases were obese compared to
      only 6% of IDDM cases. The study revealed that diabetes mellitus is a common
      chronic disease in children and young Libyan Arabs. It has shown that NIDDM in
      Benghazi is twofold higher in females than in males in the 15- to 34-year age
      group. It has also shown that age per se is not a reliable criterion for the
      classification of diabetes into IDDM and NIDDM.

PMID- 8858206
TI  - Standardization of HbA1c value and its comparison to immunoassay--two years of
      experience.
AB  - In spite of the routine use of hemoglobin Alc (HbAlc) value to guide diabetes
      therapy, substantial differences have been noted between results obtained by
      different instruments and laboratories. It was suggested that confusion between
      the terms used for HbA1c, i.e. between "total HbA1c' which includes labile
      content, and "stable HbA1c', which does not, may account for some of these inter
      instrument and inter-laboratory differences. However, an undesirable difference
      was found even in measurements of only the stable component of HbAlc using the
      two most commonly used HPLC analyzers in our country. We found that a two-point
      calibration using lyophilized hemoglobin at lower and higher ranges was effective
      in matching up results of HbA1c measurement. This finding was concordant with a
      report by the Committee of the Japan Diabetes Society and other reports. Two
      methods of HbA1c immunoassay, one performed with the DCA 2000 automated analyzer
      and another performed using the Liquitech kit or a general automated analyzer,
      were evaluated and found to perform as well as HPLC analyzers in all respects
      except precision. The results derived from immunoassay were in good agreement
      with the calibrated results by HPLC, with (Liquitech) and without (DCA 2000)
      conversions.

PMID- 8858207
TI  - Restricted geographical extension of the association of a glucagon receptor gene
      mutation (Gly40Ser) with non-insulin-dependent diabetes mellitus.
AB  - A mutation within the glucagon receptor gene (GRG) at codon 40 (Gly40Ser) was
      reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM) in
      France and Sardinia. Since the frequency of the mutation, about 5% in the French
      and 8% in the Sardinian group was higher than that of any of the candidate gene
      mutations described so far, it appeared to be relevant to determine the
      prevalence within different populations. While a single mutation has not been
      found recently either in a Japanese, a Finnish or a Dutch cohort, but only in a
      British study in 2.2% of NIDDM patients, in this study we investigated the
      association of this mutation with NIDDM in 104 German patients by polymerase
      chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). None
      of the German NIDDM patients had a Gly40Ser mutation. The results indicate that
      the mutation plays little role in susceptibility to NIDDM in this German region,
      and also indicate the genetic heterogeneity in NIDDM, and further emphasize the
      importance of studies in different ethnic groups.

PMID- 8858208
TI  - Lack of acute insulin effect on plasma endothelin-1 levels in humans.
AB  - Acute hyperinsulinemia does not increase circulating ET-1 levels in subjects with
      normal and deranged glucose metabolism.

PMID- 8858209
TI  - The harmony of the spheres: inducible nitric oxide synthase and related genes in
      pancreatic beta cells.
AB  - The radical nitric oxide (NO) is a possible mediator of pancreatic beta-cell
      damage in insulin-dependent diabetes mellitus (IDDM). NO is produced by the
      enzyme nitric oxide synthase (NOS), in a reaction where arginine is the main
      substrate. There are different isoforms of NOS, but in the context of immune
      mediated beta-cell damage the inducible form of NOS (iNOS) is the most relevant.
      The beta-cell iNOS is similar and encoded by the same gene on chromosome 17 as
      the iNOS expressed in macrophages and other nucleated cells. iNOS activation
      depends on gene transcription and de novo enzyme synthesis, and NO seems to
      induce a negative feedback on iNOS expression. While iNOS mRNA is induced by
      interleukin-1 beta (IL-1 beta) alone in rodent insulin-producing cells, a
      combination of two (IL-1 beta + interferon gamma) (IFN-gamma) or three (IL-1 beta
      + IFN gamma + tumour necrosis factor alpha) cytokines is required for iNOS
      activation in human pancreatic islets. The promoter region of the murine iNOS
      gene has at least 25 binding sites for different transcription factors, and the
      nuclear transcription factor kappa B is necessary for cytokine-induced iNOS
      transcription in both rodent and human pancreatic islets. The nature of other
      transcription factors relevant for iNOS regulation in these cells remains to be
      determined. Induction of iNOS is paralleled by induction of several other
      cytokine-dependent genes in beta cells, including argininosuccinate synthetase,
      cyclooxygenase and manganese superoxide dismutase. Some of these genes may
      contribute to beta-cell damage, while others are probably involved in beta-cell
      defence and/or repair. Regulation of iNOS and other related genes in beta cells
      is complex, and differs in several aspects from that observed in macrophages.
      There are also important differences in iNOS regulation between rodent and human
      pancreatic islets. A detailed knowledge of the molecular regulation of these
      genes in beta cells may be instrumental in the development of new approaches to
      prevent beta-cell destruction in early IDDM.

PMID- 8858210
TI  - Cloning of human pancreatic islet large conductance Ca(2+)-activated K+ channel
      (hSlo) cDNAs: evidence for high levels of expression in pancreatic islets and
      identification of a flanking genetic marker.
AB  - Insulin secretion from pancreatic beta cells is dependent on membrane potential
      changes that result from the concerted regulation of multiple ion channels. Among
      the distinct K+ channels known to be expressed in beta cells, large conductance
      Ca(2+)-activated K+ channels have been suggested to play an important role in
      stimulus-secretion coupling. In the course of a strategy to identify transcripts
      that are enriched in human pancreatic islet cells, we isolated a partial cDNA
      encoding a human large conductance Ca(2+)-activated K+ channel mRNA (hSlo).
      Northern analysis of mRNA showed that among a panel of human tissues hSlo is
      expressed at its highest levels in pancreatic islets. Screening of human
      insulinoma and islet cDNA libraries with the partial cDNA resulted in the
      isolation of 19 hSlo cDNAs. These comprised three splice variants: one shared the
      common underlying structure of previously reported Slo cDNAs, another variant
      encoded a novel 60-amino acid insertion in the putative Ca(2+)-sensing domain of
      hSlo, while the third group of clones had an alternate exon encoding eight amino
      acids in the predicted COOH-terminal end. Analysis of somatic-cell hybrids
      containing different portions of chromosome 10 indicated that hSlo maps to
      chromosome 10q22.2-q23.1. Furthermore, high resolution localization was obtained
      by analysis of genome-wide radiation hybrids and the CEPH "B" mega-YAC library,
      both of which identified for the first time a highly polymorphic genetic marker
      (D10S195) linked to hSlo. These studies provide tools with which to explore the
      physiological role of Ca(2+)-activated K+ channel proteins in pancreatic islets,
      and also to investigate the contribution of this locus to the inherited
      susceptibility to non-insulin-dependent diabetes mellitus.

PMID- 8858211
TI  - GTPase activating protein activity for Rab4 is enriched in the plasma membrane of
      3T3-L1 adipocytes. Possible involvement in the regulation of Rab4 subcellular
      localization.
AB  - The small guanosine 5'-triphosphate (GTP)ase Rab4 has been suggested to play a
      role in insulin-induced GLUT4 translocation. Under insulin stimulation, GLUT4
      translocates to the plasma membranes, while Rab4 leaves the GLUT4-containing
      vesicles and becomes cytosolic. Rab proteins cycle between a GTP-bound active
      form and a guanosine 5'-diphosphate (GDP)-bound inactive form. The intrinsic
      GTPase activity of Rab proteins is low and the interconversion between the two
      forms is dependent on accessory factors. In the present work, we searched for a
      GTPase activating protein (GAP) for Rab4 in 3T3-L1 adipocytes. We used a
      glutathione-S-transferase (GST)-Rab4 protein which possesses the properties of a
      small GTPase (ability to bind GDP and GTP and to hydrolyse GTP) and can be
      isolated in a rapid and efficient way. This GAP activity was observed in 3T3-L1
      adipocyte lysates, and was able to accelerate the hydrolysis of the [alpha
      32P]GTP bound to GST-Rab4 into [alpha-32P]GDP. This activity, tentatively called
      Rab4-GAP, was also present in 3T3-L1 fibroblasts. The Rab4-GAP activity was
      present in total membrane fractions and nearly undetectable in cytosol. Following
      subcellular fractionation, Rab4-GAP was found to be enriched in plasma membranes
      when compared to internal microsomes. Insulin treatment of the cells had no
      effect on the total Rab4-GAP activity or on its subcellular localization. Taking
      our results together with the accepted model of Rab cycling in intracellular
      traffic, we propose that Rab4-GAP activity plays a role in the cycling between
      the GTP- and GDP-bound forms of Rab4, and thus possibly in the traffic of GLUT4
      containing vesicles.

PMID- 8858212
TI  - Impairment of afferent arteriolar myogenic responsiveness in the galactose-fed
      rat is prevented by tolrestat.
AB  - By permitting the separation of increased aldose reductase activity from
      hyperglycaemia and insulin deficiency, galactose-fed rats have constituted a
      useful model for investigating diabetic complications. Such rats manifest an
      impaired afferent arteriolar responsiveness to pressure similar to that of rats 4
      to 6 weeks after induction of diabetes with streptozotocin. In the present study,
      we investigated whether treatment of galactose-fed rats with the aldose reductase
      inhibitor tolrestat prevent this autoregulatory defect and whether the blunted
      afferent arteriolar responsiveness to pressure is associated with impaired
      responsiveness to angiotensin II. Pressure-induced vasoconstriction of afferent
      arterioles was assessed in kidneys made hydronephrotic to allow direct
      visualization of renal microvessels by computer-assisted image processing. Vessel
      diameters were quantitated following stepwise increments of renal perfusion
      pressure (RAP; from 80 to 180 mm Hg) in kidneys of control rats and rats fed a
      diet for 2 weeks with 50% galactose with or without tolrestat. Subsequent to the
      pressure studies, angiotensin II (0.3 nmol/l) was added to the perfusate, and
      vessel diameters were reassessed. Control rats exhibited progressive afferent
      arteriolar vasoconstriction when RAP was increased from 80 to 180 mm Hg (-17.2 +/
      1.0%; p < 0.001). In contrast, myogenic responses to increases in pressure were
      absent in the arterioles of the galactose-fed rats (-4.1 +/- 1.9%; N.S.).
      Treatment with tolrestat completely prevented this impairment in afferent
      arteriolar responsiveness (-16.5 +/- 1.8%; p < 0.001). The angiotensin II-induced
      vasoconstriction did not differ between control rats and galactose-fed rats. We
      conclude that increased aldose reductase activity contributes to impaired renal
      auto-regulation in galactose-fed rats, a model of diabetic nephropathy, but is
      not involved in the loss of afferent arteriolar responsiveness to angiotensin II.

PMID- 8858213
TI  - Diabetes mellitus affects prostaglandin E2 levels in mouse embryos during
      neurulation.
AB  - The arachidonic acid cascade leading to prostaglandins has been implicated in
      diabetic embryopathy. Both arachidonic acid and prostaglandin E2 reverse the
      teratogenic effects of high glucose concentrations on neural tube development in
      mouse embryos in culture. Arachidonic acid supplementation also protects against
      diabetes-induced neural tube defects in vivo. In the present study, prostaglandin
      E2 was measured directly in embryos from normal and diabetic mice. In normal mice
      a clear developmental pattern was seen. Prostaglandin E2 levels were high during
      early formation of the cranial neural folds (day 8), declined during convergence
      and fusion of the cranial neural folds to form the neural tube (day 9), and were
      low after neurulation was complete (days 10 and 11). In addition, evidence in
      this study indicates that embryos have cyclooxygenase activity capable of
      generating prostaglandin E2 during a brief developmental period preceding neural
      tube closure. In embryos from mice made diabetic (> 13.9 mmol/l glucose) with
      streptozotocin, prostaglandin E2 levels were significantly lower than normal
      during early development of the cranial neural folds (day 8), but similar to
      normal after the cranial neural tube had closed (late day 9 and day 10). The
      findings suggest that diabetes mellitus, as ascertained by high blood glucose,
      promotes cranial neural tube malformations by causing a functional deficiency of
      prostaglandin E2 during early neurulation. Whether the altered PGE2 pattern in
      the embryo indicates a diabetic effect on the arachidonic acid-prostaglandin
      cascade in cells of the embryo or in cells of extraembryonic or maternal tissues
      is uncertain.

PMID- 8858214
TI  - Adipocyte lipolysis in normal weight subjects with obesity among first-degree
      relatives.
AB  - In this study we investigated whether fat cell lipolysis could be involved in the
      aetiology of obesity by comparing non-obese subjects with (Hob) or without
      (Hnorm) a family trait for overweight. A family history of obesity was present
      when at least one of the first-degree relatives had body mass index of 27 kg/m2
      or more. Twenty-seven healthy, drug-free non-obese adult subjects were
      investigated; 13 were Hob and the remaining 14 were Hnorm. Eleven Hob had at
      least one obese parent. Isolated fat cells from abdominal subcutaneous adipose
      tissue were incubated in vitro. Glycerol release (lipolysis index), mRNA levels
      and enzymatic activity of hormone-sensitive lipase and radioligand binding to
      beta 1- and beta 2-adrenoceptors were determined. The lipolytic effects of
      noradrenaline (major endogenous lipolytic agent), isoprenaline (a non-selective
      beta-adrenoceptor agonist), forskolin (a direct activator of adenylyl cyclase)
      and dibutyryl cyclic AMP (activating protein kinase and thereby hormone-sensitive
      lipase) were reduced by about 50% (p from 0.001 to 0.01). The maximum activity of
      hormone-sensitive lipase was reduced 50% in Hob (p < 0.05) and correlated with
      the lipolytic responsiveness of fat cells in the whole population (r = 0.71).
      However, there was no difference between the groups in steady-state mRNA levels
      for the enzyme. Beta 1-->, beta 2- and alpha 2-adrenoceptor sensitivity as well
      as beta 1- and beta 2-adrenoceptor numbers were normal in Hob. Fasting plasma
      insulin was 49.1 and 32.6 pmol/l, respectively in Hob and Hnorm (p = 0.01). There
      was, however, no significant correlation between lipolysis in vitro and plasma
      insulin. Thus, lipolytic catecholamine resistance in fat cells, at least partly
      due to impaired function of hormone-sensitive lipase, is an adipocyte abnormality
      associated with a family tendency to obesity.

PMID- 8858215
TI  - Nutritional intake of 2868 IDDM patients from 30 centres in Europe. EURODIAB IDDM
      Complications Study Group.
AB  - The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was
      designed to measure the prevalence of diabetic complications in stratified
      samples of European insulin-dependent diabetic (IDDM) patients. As diet may be
      related to diabetic complications, nutritional intake was analysed in the study
      population. The aims of this first nutritional paper are to describe the nutrient
      intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe,
      to investigate the degree of regional differences in nutrient intake and to
      compare current intakes with recommended levels. Nutritional intake from 1458
      male and 1410 female IDDM patients was assessed by a validated 3-day record (two
      weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was
      2390 +/- 707 kcal/day. Mean protein intake was 1.5 +/- 0.5 g/kg body weight.
      Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the
      total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from
      saturated fat. The Italian centres reported lower total and saturated fat intakes
      compared with other centres. Recommendations from the Diabetes and Nutrition
      Study Group of the EASD for total fat, saturated fatty acids and carbohydrate
      were only achieved by 14%, 14% and 15% of patients, respectively. The data of the
      present study clearly indicate current problems in the nutritional intake of
      European IDDM patients. These findings contribute to the definition of future
      targets in the nutritional management of IDDM patients, to be achieved as part of
      the initiatives taken by the St. Vincent Declaration action programme.

PMID- 8858216
TI  - Familial factors determine the development of diabetic nephropathy in patients
      with IDDM.
AB  - To evaluate familial factors in the development of diabetic nephropathy in
      insulin-dependent diabetes mellitus (IDDM) we examined concordance for diabetic
      nephropathy in families with multiple IDDM siblings. Families (n = 110) were
      identified through Joslin Clinic patients (probands) with a sibling having IDDM.
      To be eligible, the probands' and siblings' ages at IDDM diagnosis were less than
      21 years, and IDDM duration was more than 15 years for probands and more than 10
      years for siblings. Mean post-pubertal diabetes duration was 23 years for
      probands (n = 110) and 21 years for siblings (n = 125). Nephropathy history was
      determined by medical record review for deceased patients and those with
      persistent proteinuria or end-stage renal disease to ascertain the date of onset
      of persistent proteinuria. For patients without documented nephropathy, the
      albumin/creatinin ratio was measured in multiple urine samples. The cumulative
      incidence of persistent proteinuria according to post-pubertal duration of IDDM
      was determined by life-table analysis. For probands and siblings combined, the
      cumulative incidence of advanced diabetic nephropathy after 30 years of IDDM was
      35%, but the risk in siblings varied according to the proband's renal status. The
      cumulative risk in siblings after 25 years of IDDM (post-puberty) was 71.5% if
      the proband had persistent proteinuria but only 25.4% if the proband did not (p <
      0.001). A difference of nearly 50% in the risk to IDDM siblings, depending upon
      the IDDM proband's renal status, is consistent with a major gene effect that
      predisposes an individual with IDDM to develop advanced diabetic nephropathy.

PMID- 8858217
TI  - The role of glycation cross-links in diabetic vascular stiffening.
AB  - Previous studies have shown that biomechanical analysis of aorta from diabetic
      subjects reveals a marked increase in stiffness compared to aorta from age
      matched control subjects. In the present paper we have proposed that this
      increased stiffness can be attributed to glycation-induced inter-molecular cross
      links based on a direct analysis of the two known glycation cross-links, the
      fluorescent pentosidine and the non-fluorescent NFC-1. There was a significant
      difference in the increase in concentration of both cross-links with increasing
      age for both the intima (p < 0.0025) and the media (p < 0.0005) from the diabetic
      compared to the control subjects, but no correlation with the mature enzymic
      cross-link hy droxylysyl-pyridinoline. Finally, we have obtained a significant
      correlation of stiffness with both glycation cross-links (NFC-1, r = 0.86; p <
      0.005 and pentosidine r = 0.75, p < 0.05), but the concentration of NFC-1 is
      about 50 times greater than that of pentosidine, indicating that it is the major
      glycation cross-link responsible for the stiffening of the aorta.

PMID- 8858218
TI  - Increased expression of low-affinity insulin receptor isoform and insulin/insulin
      like growth factor-I hybrid receptors in term placenta from insulin-resistant
      women with gestational hypertension.
AB  - Gestational hypertension is associated with insulin-resistance; insulin and
      insulin-like growth factor-1 (IGF-1), acting through their receptors, play a role
      in the growth of the feto-placental unit. Since both receptors are exposed to the
      maternal circulation, it has been suggested that maternal metabolic abnormalities
      might affect placental insulin (HIR) and IGF-1 (IGF-1R) receptors. To clarify
      this issue, we characterized HIR and IGF-1R in placenta at term from normal
      women, normoinsulinaemic women with gestational hypertension (NGH), and
      hyperinsulinaemic women with gestational hypertension (HGH). Insulin binding was
      decreased in HGH women (B/T 0.12 +/- 0.03) compared to control and NGH women (B/T
      0.18 +/- 0.07, p < 0.036; and 0.22 +/- 0.5, p < 0.009 respectively). Receptor
      affinity was lower in HGH women (ED50 0.95 +/- 0.32 nmol/l) than control and NGH
      women (ED50 0.42 +/- 0.19 nmol/l, p < 0.01; and 0.40 +/- 0.1 nmol/l, p < 0.007,
      respectively), whereas low-affinity Ex11+ isoform was higher in HGH women (Ex11+
      50 +/- 7, %) than in control and NGH women (Ex11+ 34 +/- 9%, p < 0.001; and 39 +/
      4%, p < 0.01, respectively). Increased expression of Ex11+ isoform was
      correlated with ED50 (r = 0.71; p < 0.002) and insulinaemia (r = 0.70, p <
      0.002). IGF-I binding was increased in HGH women (B/T 0.17 +/- 0.03) compared to
      control and NGH women (B/T 0.09 +/- 0.05, p < 0.002; and 0.11 +/- 0.03, p <
      0.002, respectively). IGF-IR affinity was similar in the three groups. The
      percentage of insulin/IGF-I hybrid receptors was increased in HGH women (85 +/-
      3%) compared to control and NGH women (68 +/- 7%, p < 0.001; and 63 +/- 9%, p <
      0.001, respectively), and was positively correlated with insulinaemia (r = 0.62,
      p < 0.018), ED50 of insulin binding (r = 0.62, p < 0.05), and maximal IGF-I
      binding (r = 0.69, p < 0.004); whereas it was inversely correlated with maximal
      insulin binding (r = -0.69, p < 0.004). Results provide the first evidence for
      altered expression of insulin/IGF-I hybrids found in insulin-resistance states.

PMID- 8858219
TI  - Insulin-like growth factor-I in man enhances lipid mobilization and oxidation
      induced by a growth hormone pulse.
AB  - Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I
      (IGF-I) administration. The aim of the study was to examine whether IGF-I alters
      the metabolic response to a GH pulse. Seven healthy male subjects (age 27 +/- 4
      years, BMI 21.8 +/- 1.7 kg/m2) were treated with NaCl 0.9% (saline) or IGF-I (8
      micrograms.kg-1.h-1) for 5 days by continuous subcutaneous infusion in a
      randomized, crossover fashion while receiving an isocaloric diet (30 kcal.kg
      1.day-1). On the third treatment day an intravenous bolus of 0.5 U GH was
      administered. Forearm muscle metabolism was examined by measuring arterialized
      and deep venous blood samples, forearm blood flow by occlusion plethysmography
      and substrate oxidation by indirect calorimetry. IGF-I treatment significantly
      reduced insulin concentrations by 80% (p < 0.02) and C-peptide levels by 78% (p <
      0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA),
      glycerol and 3-OH-butyrate levels were elevated and alanine concentration
      decreased. Forearm blood flow rose from 2.10 +/- 0.43 (saline) to 2.79 +/- 0.37
      ml.100ml-1. min-1 (IGF-I) (p < 0.02). GH-pulse: 10 h after i.v. GH injection
      serum GH peaked at 40.9 +/- 7.4 ng/ml. GH did not influence circulating levels of
      total IGF-I, C-peptide, insulin or glucose, but caused a further increase in
      NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and
      ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose
      from 702 +/- 267 (saline) and 885 +/- 236 (IGF-I) to 963 +/- 215 (saline) (p <
      0.05) and 1815 +/- 586 mumol/l (IGF-I) (p < 0.02), respectively; after 5 h, 3-OH
      butyrate rose from 242 +/- 234 (saline) and 340 +/- 280 (IGF-I) to 678 +/- 638
      (saline) (p < 0.02) and 1115 +/- 578 mumol/l (IGF-I) (p < 0.02) respectively.
      After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only
      in the subjects treated with IGF-I: from 44 +/- 195 to 300 +/- 370 after 20 min
      (p < 0.03) and to 287 +/- 91 nmol.100 ml-1. min-1 after 120 min (p < 0.02). In
      conclusion, the lipolytic and ketogenic response to GH was grossly enhanced
      during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was
      increased.

PMID- 8858220
TI  - Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic
      dysinnervation in newly diagnosed and long-term IDDM patients.
AB  - To investigate the presence of autoantibodies against sympathetic nervous tissue
      and their correlation with cardiac sympathetic dysinnervation in insulin
      dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26 +/- 6 years) and
      48 long-term IDDM patients (age 40 +/- 13 years, duration of diabetes 22 +/- 12
      years) without myocardial perfusion abnormalities (normal 99mTC
      methoxyisobutylisonitrile uptake) were assessed for myocardial 123I-metaiodo
      benzylguanidine (123I-MIBG) uptake and complement-fixing sympathetic ganglia (CF
      SG) autoantibodies. Both groups of patients were also studied for islet cell
      antibodies (ICA) and ECG-based cardiac autonomic neuropathy. Eighty control
      subjects (age 18-49 years) were investigated for CF-SG autoantibodies. Eight
      newly diagnosed (40%) and 12 long-term (25%) IDDM patients exhibited CF-SG
      autoantibodies, compared to 4 control subjects (5%; p < 0.01, p < 0.05). In long
      term diabetic patients, the reduction of global but not of regional myocardial
      123I-MIBG uptake correlated with CF-SG autoantibodies (r = 0.34, p = 0.02). Newly
      diagnosed diabetic patients did not show an association between CF-SG
      autoantibodies and global or regional myocardial 123I-MIBG uptake. ECG-based
      cardiac autonomic neuropathy (> or = two of five cardiac reflex tests abnormal)
      was present in 22 and absent in 26 long-term IDDM patients, of whom 9 (41%) and 3
      (12%), respectively were positive for CF-SG autoantibodies (p = 0.02). Only 1
      newly diagnosed IDDM patient demonstrated ECG-based cardiac autonomic neuropathy
      and was also positive for CF-SG autoantibodies. Although they are somewhat
      suggestive, results concerning autoantibodies against sympathetic nervous tissue
      and cardiac sympathetic dysinnervation do not strongly support the view that
      autoimmune mechanisms play a major role in the pathogenesis of cardiac
      sympathetic neuropathy in IDDM.

PMID- 8858221
TI  - Measurement of glucose metabolism and insulin secretion during normal pregnancy
      and pregnancy complicated by gestational diabetes.
AB  - Gestational diabetes affects 2-3% of pregnant women and is associated with foetal
      complications including macrosomia and an increased likelihood of developing
      diabetes in later life. We have therefore studied seven women with gestational
      diabetes and five control women both during the third trimester of pregnancy and
      again 2-3 months post-partum, using the minimal model analysis of the frequently
      sampled labelled ([6,6-2H2]-glucose) intravenous glucose tolerance test. Glucose
      tolerance (glucose Kd) was significantly reduced in the women with gestational
      diabetes compared with the normal pregnant women both in pregnancy (1.16 +/- 0.11
      vs 1.78 +/- 0.23%/min; p < 0.05) and post-partum (1.47 +/- 0.22 vs 2.59 +/-
      0.43%/min; p < 0.05) and increased significantly in the control women after
      delivery (p < 0.05). Glucose effectiveness was not significantly different
      between the women with gestational diabetes and the control group either during
      or after pregnancy. Insulin sensitivity was significantly lower during pregnancy
      than after delivery in the women with gestational diabetes (p < 0.05). There was
      no significant difference in basal insulin secretion in the two groups during
      pregnancy or post-partum. However, during pregnancy the control subjects
      significantly increased (p < 0.001) their insulin secretion over a period of 20
      min in response to an intravenous glucose tolerance test (96.2 +/- 42.7 pmol/kg)
      compared with post-partum values (58.3 +/- 25.2 pmol/kg) while in the women with
      gestational diabetes insulin secretion was similar in pregnancy (65.5 +/- 9.3
      pmol/kg) and after delivery (57.7 +/- 15.7 pmol/kg). These data suggest that the
      glucose intolerance in gestational diabetes compared to normal pregnancy is due
      to reduced insulin sensitivity and an impaired ability in gestational diabetes to
      increase insulin secretion in response to glucose.

PMID- 8858223
TI  - Enzyme-to-enzyme channelling of symmetric Krebs cycle intermediates in pancreatic
      islet cells.
AB  - Tumoural islet cells of the RINm5F line were incubated for 120 min in the
      presence of [2-13C]propionate (10 mmol/l), and the 13C enrichment of lactate
      released in the incubation medium was monitored by 13C nuclear magnetic
      resonance. The C3/C2 ratio of resonance areas was much lower than that found with
      naturally 13C-enriched lactate. This reveals that symmetric Krebs cycle
      intermediates undergo oriented transfer in the sequence of reactions catalysed by
      succinate thiokinase, succinate dehydrogenate and fumarase in the mitochondria of
      islet cells.

PMID- 8858222
TI  - The effect of acute hyperglycaemia on small intestinal motility in normal
      subjects.
AB  - The effects of hyperglycaemia on postprandial small intestinal motor activity are
      unclear. Duodenal and jejunal pressures and duodeno-caecal transit were measured
      in eight healthy male volunteers during euglycaemia (blood glucose 4-6 mmol/l)
      and hyperglycaemia (blood glucose 12-15 mmol/l). Duodenal and jejunal pressures
      were recorded with a manometric assembly during intraduodenal infusion of 100 ml
      nutrient liquid comprising 14% protein, 31.5% fat and 54.5% carbohydrate together
      with 15 glactulose. Duodeno-caecal transit was determined by a breath hydrogen
      technique. The number of duodenal (p < 0.05) and jejunal (p < 0.01) pressure
      waves, excluding phase III episodes was reduced during hyperglycaemia compared to
      euglycaemia Hyperglycaemia was associated with earlier onset of phase III
      activity (30 +/- 12 vs 132 +/- 20 min; p < 0.05) Duodeno-caecal transit was
      slower during hyperglycaemia when compared to euglycaemia (114 +/- 17 vs 49 +/- 6
      min, p < 0.01). We conclude that induced hyperglycaemia has major effects on
      postprandial small intestinal motility. The reduction in duodenal and jejunal
      motor activity is likely to explain the retardation of small intestinal transit
      during hyperglycaemia.

PMID- 8858224
TI  - Insulin increases plasma leptin concentrations in normal subjects and patients
      with NIDDM.
AB  - Insulin is known to increase expression of the ob gene product leptin in adipose
      tissue of rodents. We determined whether insulin increases circulating leptin
      concentrations in humans, and whether this effect might be altered in patients
      with noninsulin-dependent diabetes mellitus (NIDDM). Plasma leptin concentrations
      were determined during an 8.5-h hyperinsulinaemic clamp (serum free insulin
      approximately 480 pmol/l) and during an 8.5-h infusion of physiological NaCl
      solution (saline) in eight normal subjects (age 51 +/- 3 years, BMI 26.3 +/- 0.6
      kg/m2, fasting plasma glucose 5.6 +/- 0.2 mmol/l) and seven patients with NIDDM
      (age 54 +/- 2 years, 27.0 +/- 0.9 kg/m2, 11.1 +/- 0.8 mmol/l). Fasting serum
      insulin level correlated with plasma leptin (r = 0.72, p < 0.005), even after
      adjusting for the percentage of body fat (p < 0.005). During the insulin
      infusion, a significant increase in the plasma leptin concentration was observed
      after 6 h (37 +/- 14%; 5.2 +/- 0.8. vs 3.9 +/- 0.6 ng/ml, 6 vs 0 h, p < 0.05) in
      the normal subjects and after 8.5 h (38 +/- 11%; 7.1 +/- 1.0 vs 5.5 +/- 0.9
      ng/ml, 8.5 vs 0 h, p < 0.05) in the patients with NIDDM. During the saline
      infusion, plasma leptin concentrations decreased significantly in the normal
      subjects by 11 +/- 1% (p < 0.005) and in the patients with NIDDM by 14 +/- 1% (p
      < 0.01) after 2 h. During the infusion of insulin as compared to saline, plasma
      leptin concentrations were 32 +/- 13 (p < 0.05), 53 +/- 14 (p < 0.001), 106 +/-
      15 (p < 0.001) and 165 +/- 21 (p < 0.001) % higher at 2, 4, 6 and 8.5 h in the
      normal subjects, and 11 +/- 9 (p < 0.05), 27 +/- 10 (p < 0.05), 58 +/- 7 (p <
      0.001) and 106 +/- 13 (p < 0.001) % higher in the patients with NIDDM,
      respectively. No differences were observed in plasma leptin concentrations
      between the normal subjects and patients with NIDDM, under any conditions. We
      conclude that prolonged exposure to insulin increases plasma leptin
      concentrations in humans implying a role for insulin in chronic but not acute
      regulation of plasma leptin concentrations. The decrease in plasma leptin
      concentrations during saline infusion was greater than that expected on the basis
      of change in serum insulin concentrations, suggesting that factors other than
      insulin also contribute to regulation of plasma leptin concentrations.

PMID- 8858225
TI  - Is the minimal model too minimal?

PMID- 8858226
TI  - Assignment of the IA-2 gene encoding an autoantigen in IDDM to chromosome 2q35.

PMID- 8858227
TI  - Are insulin resistance and atherosclerosis the consequences of oxidative stress?

PMID- 8858228
TI  - Long-term follow-up after treatment of common bile duct stones by extracorporeal
      shock-wave lithotripsy.
AB  - BACKGROUND AND STUDY AIMS: The efficacy of extracorporeal shock-wave lithotripsy
      (ESWL) of difficult bile duct stones that were not amenable to routine endoscopic
      extraction was assessed, with evaluation of the long-term follow-up after
      successful treatment. PATIENTS AND METHODS: Fifty-four patients (mean age 74
      years, range 33-92) were treated with ESWL for difficult bile duct stones.
      Treatment was performed either with the Dornier HM3 kidney lithotriptor (49
      patients) or with the MPL 9000 lithotriptor (five patients). RESULTS: Stone
      disintegration was achieved in 50 patients (93%), with complete stone clearance
      in 45 patients (83%) (mean 1.2 session). Patients with successful stone removal
      after one session had significantly smaller stones than patients with treatment
      failure (20 +/- 9 versus 27 +/- 8 mm; p < 0.05). An intrahepatic location of
      stones was significantly associated with treatment failure (p < 0.005). Serve
      complications occurred in 7% (procedure-related 5%), with a 30-day mortality rate
      of 0% (in-hospital mortality rate of 2%). Minor side effects such as fever,
      petechiae, and mild arrhythmias were frequent (37%), and microhematuria (95%)
      occurred in nearly all of the patients. Symptomatic recurrent bile duct stones
      were observed in two patients (5%) after three and four years, respectively (mean
      follow-up 5.3 years). CONCLUSION: Extracorporeal shock wave lithotripsy
      represents a safe and effective treatment modality for difficult bile duct
      stones, with a low rate of symptomatic recurrences.

PMID- 8858229
TI  - Wallstents for metastatic biliary obstruction.
AB  - BACKGROUND AND STUDY AIMS: In patients with obstruction of the common bile duct
      caused by primary pancreaticoblliary tumors, Wallstents have been shown to remain
      patent for a median duration of 273 days (range: 14-363). However, in one study
      that included both patients with primary pancreaticobillary malignancies and
      patients with metastatic malignant disease, the reported median Wallstent patency
      was found to be significantly shorter. We have studied the patency of Wall-stents
      in patients with metastatic billary obstruction. PATIENTS AND METHODS: All
      patients who had received a Wallstent for metastatic biliary obstruction between
      January 1990 and August 1994 were analyzed retrospectively. Follow-up was
      achieved by contacting referring physicians and general practitioners, and lasted
      up to the end of the study period (November 1994) or death of the patient. Follow
      up was discontinued if a polyethylene stent was inserted through the Wallstent
      for treatment of stent dysfunction. RESULTS: 28 patients were identified,
      including 14 men and 14 women, with a mean age of 61.3 years (range 24-87). Long
      term follow-up was possible in 27 patients (96%), for a median duration of 140
      days (range 29- 561). Eleven patients died during the study period, and there
      were three deaths related to Wallstent dysfunction. The median duration of
      Wallstent patency was 265 days (range 11-519). Wallstent obstruction occurred in
      13 patients; seven patients presented with cholangitis, six patients had
      jaundice. The cause of obstruction was established at endoscopic retrograde
      cholangiopancreatography in ten patients: seven had tumor ingrowth, and three had
      tumor overgrowth. Treatment consisted of insertion of a polyethylene stent in
      seven and placement of a second Wallstent in three patients. CONCLUSION: In
      patients with metastatic obstruction of the common bile duct, the duration of
      patency of Wallstents is comparable to that reported in series of Wallstents for
      primary pancreaticobiliary malignancies.

PMID- 8858230
TI  - Prospective comparison of nasal versus oral insertion of a thin video endoscope
      in healthy volunteers.
AB  - BACKGROUND AND STUDY AIMS: Attempts have been made to improve patient's tolerance
      of upper gastrointestinal endoscopy and to decrease the need for sedation, using
      thinner endoscopes and a nasal introduction route. We prospectively compared the
      oral and nasal routes in volunteers, using a thin prototype video endoscope.
      METHODS: Ten healthy volunteers underwent two upper gastrointestinal endoscopies
      in a random order on two different days, with the procedure being carried out by
      a single experienced endoscopist. Parameters assessed were the tolerance of scope
      insertion and the assessment of the entire procedure (0-10 scale), the method of
      insertion preferred by the volunteers, the completeness of the examination
      (assessed by an independent endoscopist), and the time required for the
      procedure. RESULTS: In one patient, nasal insertion failed, and she was excluded
      from further analysis. The insertion of the scope was easier via the oral route,
      as reflected in a shorter examination time (mean 165 vs. 210 seconds, p = 0.017)
      and patients' tolerance for the scope insertion (mean score: 8 for oral vs. 4 for
      nasal route; p = 0.03). On the other hand, gagging occurred more frequently
      during oral endoscopy (6/9 vs 1/9, p = 0.05). Three of the volunteers in each
      case preferred the oral or the nasal route, and three were not decided, in case
      of a repeated endoscopy. Similarly, the overall tolerance for the procedure did
      not between the two groups. CONCLUSION: Thin-diameter gastroscopes seem to
      improve patient's tolerance. In this small study in volunteers, nasal
      introduction showed no overall benefit over oral introduction. Modifications of
      the scope to achieve better nasal passage are necessary.

PMID- 8858231
TI  - Diagnosis of borderline adenomas of the stomach by endoscopic mucosal resection.
AB  - BACKGROUND AND STUDY AIMS: The correct histological diagnosis of gastric
      borderline adenomas is often difficult, especially in excluding malignancy, since
      the usual diagnostic methods, such as radiography and histological examination of
      forceps biopsy specimens, are of limited accuracy. The aim of this study was to
      retrospectively analyze the value of endoscopic mucosal resection in establishing
      the correct diagnosis of borderline adenomas. RESULTS: Fourteen borderline
      adenomas were finally diagnosed as containing early gastric cancer type IIa (well
      differentiated tubular adenocarcinoma) after endoscopic mucosal resection, of the
      remaining 36 tubular adenomas, six represented mild dysplasia, 24 moderate
      dysplasia, and six severe dysplasia. Most parts of the 14 adenomas containing
      early gastric cancers had regions of structural atypia, and cellular atypia was
      moderate in all. Seven of 14 cancers were completely resected, all patients being
      tumor-free after a follow-up of 33-61 months. CONCLUSIONS: These results suggest
      that diagnosing borderline adenoma on the basis of radiographic and endoscopic
      bioptic findings is generally unreliable, because biopsy specimens may not be
      representative of the entire lesion. Borderline adenomas of the stomach should be
      completely resected by endoscopic mucosal resection to obtain a final diagnosis
      and - depending on the size and type of the lesion - possibly also definitive
      treatment.

PMID- 8858233
TI  - Upper and lower gastrointestinal endoscopy: are thinner endoscopes preferable?

PMID- 8858234
TI  - ERCP versus laparoscopic surgery: the contest over common bile duct stones.

PMID- 8858232
TI  - Laparoscopic transcystic cholangioscopic lithotripsy for common bile duct stones
      during laparoscopic cholecystectomy.
AB  - BACKGROUND AND STUDY AIMS: Following the recent introduction of laparoscopic
      cholecystectomy (LC) for cholecystolithiasis, treatment of concomitant common
      bile duct (CBD) stones has been evaluated by using laparoscopic choledochotomy, a
      transcystic approach, or by means of endoscopic sphincterotomy (ES) before or
      after LC. PATIENTS AND METHODS: During laparoscopic cholecystectomy, we attempted
      lithotripsy of CBD stones using laparoscopic transcystic cholangioscopy with
      lithotripsy (LTCL), in 70 patients out of 950 laparoscopic cholecystectomies.
      Preparatory tests included laboratory values, ultrasound, and performance of
      endoscopic retrograde cholangiography (ERC) with placement of a nasobillary tube
      (without sphincterotomy). RESULTS: Introduction of the cholangioscope into the
      CBD was successful in 65 patients (92.9%) and CBD clearance was completely
      achieved by LTCL alone in 51 (78.5%). The overall success rate was therefore 73%.
      The remaining 19 cases required postoperative procedures such as extracorporeal
      shock-wave lithotripsy without ERC or ES (successful in all). The average
      hospital stay period was 9.4 days for patients in whom CBD clearance was achieved
      by LTCL alone. This period did not differ significantly from that of patients who
      underwent LC alone (8.4) days. The operation time was about 70 minutes longer for
      the LTCL group (total time 174 minutes on average) than for the LC group (107
      minutes). We did not observe any series complications during or after LTCL (mean
      follow-up period: 34 months). CONCLUSION: LTCL in combination with LC allows
      shortening of the hospital stay and a swift return to work for patients with CBD
      stones. This procedure also preserves the function of the sphincter of Oddi, so
      that the longterm prognosis for patients is likely to be very good.

PMID- 8858235
TI  - Recent publications in laparoscopic surgery: an overview.

PMID- 8858236
TI  - Prolapsing gastric polyp, an unusual cause of gastric outlet obstruction: a
      review of the pathology and management of gastric polyps.
AB  - Gastric polyps are rare and largely asymptomatic, but attract importance because
      of their strong potential to progress to carcinoma. Rarely, pedunculated polyps
      arising in the antrum may prolapse through the pylorus, causing intermittent
      gastric outlet obstruction. We describe here our experience of four cases
      collected over a ten-year period, each presenting dissimilarly with this
      phenomenon. We review the literature referring to the pathogenesis of gastric
      polyps and their association with malignancy and other disorders. We proceed to
      discuss the efficacy of barium studies versus gastroscopy in detecting these
      lesions, the relative roles and merits of endoscopic polypectomy and surgery, and
      the importance of prolonged follow-up of patients harbouring gastric polyps.

PMID- 8858237
TI  - Colon decompression using an anatomically adapted, large-caliber decompression
      probe.
AB  - Intestinal pseudo-obstruction, paralytic (e.g. postoperative or drug-induced)
      hyperdistension of the large bowel and colonic stenosis often require endoscopic
      decompression. The decompression probes currently available have the disadvantage
      of an insufficiently large diameter or inadequate adaptation to the given
      anatomic configuration of colon, or both. A new decompression probe system
      consisting of a guide wire, a 12-Fr polyethylene guide catheter, and a 24-Fr
      polyurethane decompression probe, is presented and two cases are described. The
      probe was tested in a pilot study in 16 patients. In all patients, implantation
      was successfully performed without complications. No undesired dislocation was
      observed. The introduction time varied between four and 16 minutes. Clinically
      successful decompression was achieved in 14 of the 16 patients.

PMID- 8858238
TI  - Endosonographic findings in pseudomyxoma peritonei.

PMID- 8858239
TI  - Lichen planus esophagitis with secondary candidiasis: successful combination
      treatment with ketoconazole and a corticosteroid.

PMID- 8858240
TI  - A case of portal and splenic vein thrombosis after Histoacryl injection therapy
      in gastric varices.

PMID- 8858241
TI  - Intramural rupture of the oesophagus: a case report of a unique endoscopic
      appearance.

PMID- 8858242
TI  - Laparoscopy as an adjuvant in appendectomy.

PMID- 8858243
TI  - Laser-assisted removal of a foreign body from the esophagus.

PMID- 8858244
TI  - Sequential endoscopic findings in spontaneous intramural hematoma of the
      esophagus.

PMID- 8858245
TI  - A new steerable catheter for improving the efficiency of fluoroscopy-guided laser
      lithotripsy.

PMID- 8858246
TI  - Massive loss of bile from the nasobiliary tube.

PMID- 8858247
TI  - Endosonographic follow-up after local excision of a pT1 rectal carcinoma.

PMID- 8858248
TI  - Subobstructive symptoms caused by a pedunculated polyp of the terminal ileum in
      stenosing ileocolonic Crohn's disease.

PMID- 8858249
TI  - Sigmoid perforation: a rare complication of a migrated biliary endoprosthesis.

PMID- 8858250
TI  - Endoscopic treatment of gallstone-impacted choledochocele precisely diagnosed by
      endoscopic ultrasonography.

PMID- 8858251
TI  - Idiopathic esophageal ulceration associated with human immunodeficiency virus
      infection: efficacy of thalidomide treatment.

PMID- 8858252
TI  - A new balloon system for complete dilation of self-expanding mesh stents in
      malignant esophageal stenosis.

PMID- 8858253
TI  - Guidelines of the European Society of Gastrointestinal Endoscopy (E.S.G.E.).
      Endoscopic ultrasonography. Part I: Technique and upper gastrointestinal tract.
      European Endosonography Club.

PMID- 8858254
TI  - Panendoscopy as a screening procedure for simultaneous primary tumors in head and
      neck cancer.
AB  - Head and neck cancer is often associated with second primary neoplasms. These
      cancers most commonly involve other regions of the head and neck, esophagus, and
      lung. The majority of cases are also squamous cell carcinomas. In view of this
      rather frequent occurrence of multiple primary cancers and how they adversely
      affect the patient's survival, it becomes imperative to analyze how the clinician
      can intervene effectively. One such approach is to detect multiple primaries as
      early as possible. As such, panendoscopy as a part of the tumor-staging procedure
      has been advocated by many investigators to search for simultaneous second
      primary malignant neoplasms in patients presenting with head and neck cancer. In
      a 24-month period, data were gathered from 127 consecutive patients referred to
      University Hospital, Gheni with previously untreated, squamous cell carcinomas of
      the head and neck. One hundred-eighteen patients underwent an endoscopic
      examination under general anesthesia, during which 4 simultaneous second primary
      tumors were found in 3 patients. This represents an incidence of 3.4% of
      simultaneous second primary neoplasms. The results for the different parts of the
      endoscopy are discussed and compared with literature findings. Guidelines are
      given for the initial evaluation of the head and neck cancer patient.

PMID- 8858255
TI  - Preformation of microvascular composite free flaps in the rat as an animal model.
AB  - For optimal reconstruction of large defects after tumor surgery of the head and
      neck, composite flaps may be necessary. We describe the design of microsurgically
      reanastomosed composite skin flaps, using porous polyethylene or titanium
      implants as a "back side" in an animal model. The epigastric skin of 48 healthy
      adult Wistar rats was prepared for the subdermal insertion of porous polyethylene
      implants (pore size: 100-200 microns) and titanium mesh implants having different
      forms and sizes. Two to 6 weeks after this procedure the flaps were lifted,
      transposed to the other side and the epigastric vessels were reanastomosed
      microsurgically. Eighty-three per cent of the skin flaps containing the titanium
      implants survived when the transplantation occurred 2 weeks after insertion of
      the implants. Concurrently all flaps with the implanted porous polyethylene (1 mm
      thick) showed signs of skin necrosis. Survival of the polyethylene loaded flaps
      improved to 50% when the flaps were left 4 weeks at the donor site. The influence
      of the implant form on the survival of the flaps was investigated with different
      implant shapes with flap necrosis being greatest when concave implants were used.
      Histopathological evaluation of the titanium flaps showed a thin capsule around
      the implants and a minimal inflammatory reaction. All porous polyethylene
      implants resulted in a pronounced chronic infection. Transplantation of flaps
      containing perforated metals (such as the titanium mesh) was possible 2 weeks
      after insertion of the implant, whereas neovascularization of flaps with porous
      material required more than 4 weeks growth in situ to ensure at least a 50%
      viability of the skin. An advantage of the metal implants is the possibility of
      its use in correcting form by modelling.

PMID- 8858256
TI  - Selective neck dissection in the management of squamous cell carcinoma of the
      upper digestive tract.
AB  - Selective neck dissection has been used clinically in elective treatment of
      carcinoma, although many surgeons continue to advocate modified radical or
      radical neck dissection for therapeutic management of the neck. In a
      retrospective study 167 previously untreated patients were reviewed following
      curative laser microsurgical resections of oral or pharyngeal primary tumors and
      a unior bilateral selective neck dissection. In all, 221 (54 bilateral) neck
      dissections were performed. In patients with oral primary disease lymph nodes of
      levels I-III were removed, while nodes in levels II and III were removed in
      patients with pharyngeal tumors. Level IV was dissected when several metastases
      were suspected during operation. The posterior triangle was not dissected. Lymph
      nodes were histopathologically negative in 73 patients and positive in 94
      patients. Twenty-five of these latter cases had pN1 disease, 55 had pN2b disease
      and 10 had bilateral lymph node metastases. Twenty patients in the pN0 group and
      63 patients in the pN+ group received postoperative radiotherapy (to 56.7 Gy to
      the primary site and 52.5 Gy to the neck). With a median follow-up interval of 34
      months, recurrence in the dissected neck occurred in 3 of 73 patients (4.1%) with
      pN0 disease and 6 of 90 patients (6.6%) with pN+ necks. Four patients with pN+
      necks had simultaneous recurrences at the primary site. The addition of adjuvant
      radiotherapy seemed to improve disease control in the neck and improve overall
      survival in patients with an unfavorable prognosis due to multiple metastases or
      metastases with extracapsular spread.

PMID- 8858257
TI  - Effect of growth factors on matrix synthesis by human nasal chondrocytes cultured
      in monolayer and in agar.
AB  - Reconstructive surgery of multiple areas of the body may require replacement bone
      or cartilage transplants to repair defects or lesions of skeletal tissue.
      Advances in cell and tissue culture techniques now permit synthesis of autologous
      human cartilage in vitro. Several growth factors regulate the metabolism and
      activation of cartilage cells. To enhance culture conditions and effectiveness
      for in vitro cartilage engineering, the aim of our investigations was to
      characterize the influence of transforming growth factor (TGF)-beta and basic
      fibroblast growth factor (bFGF) on human nasal septal chondrocytes. The isolated
      cells were cultured as monolayers on plastic and in soft agar. The biological
      effects of the growth factors were assessed by determining synthesis of total
      protein and proteoglycan. TGF-beta caused a dose-dependent stimulation of total
      protein as well as glycosaminoglycan synthesis by all chondrocytes cultured. This
      stimulatory effect of TGF-beta was greater for chondrocytes cultured in soft agar
      than for chondrocytes cultured on plastic. No stimulatory effects of matrix
      synthesis was observed for bFGF in either culture condition. Our results show
      that TGF-beta can be employed to enhance in vitro production of cartilage grafts
      for reconstructive surgery.

PMID- 8858258
TI  - Antiproliferative effects of the biologically active metabolite of vitamin D3
      (1,25 [OH]2 D3) on head and neck squamous cell carcinoma cell lines.
AB  - In addition to a role in calcium and phosphate homeostasis other vitamin D
      receptor (VDR) mediated effects have been discovered during the past few years
      for the biologically active metabolite of vitamin D, 1,25(OH)2D3. An
      antiproliferative, differentiation-inducing effect on non-malignant and
      neoplastic cells of different origin has now been described. We examined the
      influence of 1,25(OH)2D3 on human squamous cell carcinomas of the head and neck
      (SCCHN). A differentiated (JP-PA) and undifferentiated (LF-FR) SCCHN line was
      studied with respect to proliferative capacity (using [3H]-thymidine uptake and
      cell number) and cell cycle distribution as determined by flow cytometry (FACS).
      Both cell lines were positive for VDR, which was found to be increased after the
      addition of 10(-7) M 1,25(OH)2D3, as shown by FACS analyses. The administration
      of 1,25(OH)2D3 at a concentration between 10(-7) M and 10(-10) M caused a dose
      dependent moderate growth inhibition, as reflected by down-regulation of DNA
      synthesis (reduced [3H]-thymidine uptake) and a decrease in cell numbers. The JP
      PA cell line showed a significant growth reduction for both concentrations
      tested, whereas for LF-FR a significant inhibition was detected only for 10(-7)
      M. The addition of 10(-7) M 1,25(OH)2D3 caused a blockade in the transition of
      cells from G1 to S phase in both cell lines, with a significant accumulation of
      cells in the G0/G1 phase. Our results demonstrate a receptor-mediated, dose
      dependent inhibition of neoplastic growth by 1,25(OH)2D3 in human SCCHN lines.

PMID- 8858259
TI  - Effects of pentoxifylline and nitroprusside on guinea pig cochlear blood flow in
      relationship to various hematocrit values.
AB  - To understand better the microcirculation in the inner ear in relation to blood
      viscosity, we examined the effects of pentoxifylline (PXF) and nitroprusside (NP)
      on cochlear blood flow (CBF) in healthy adult guinea pigs in relationship to
      various hematocrit (H1) values. There was no correlation between Ht value and the
      maximum decrease of mean blood pressure after PXF infusion, whereas there was a
      positive correlation between Ht and the maximum increase in CBF. No such
      relationship was found after NP infusion. A graph plot of each animal's blood
      oxygen transport capacity (i.e., Ht/blood viscosity) was found to have a convex
      form and to increase with a shift of the peak to a higher Ht area after PXF
      infusion. These findings indicate that a decrease in blood viscosity may improve
      CBF and increase oxygen transport capacity of blood.

PMID- 8858260
TI  - Effect of cisplatin on the negative charge barrier in strial vessels of the
      guinea pig. A transmission electron microscopic study using polyethyleneimine
      molecules.
AB  - The anionic sites on the basement membrane in the cochlea are believed to act as
      a charge barrier. Using polyethyleneimine (PEI) as a cationic tracer, we examined
      the effects of cisplatin (CDDP) on anionic sites in the basement membrane in the
      cochlea. Eight Hartley-strain guinea pigs were separated into control (buffer
      administration) and CDDP groups. Ultrathin sections of the basal and third turns
      of the cochlear ducts were examined using a transmission electron microscope. A
      marked decrease of PEI distribution was noted in the strial vessels of the CDDP
      group compared to the control group. However, the two groups showed no
      significant differences in PEI particles on the basement membranes in the basilar
      and Reissner's membranes, or in the basal and third turns. These findings suggest
      that the charge barrier in the stria vascularis may be easily injured by the
      administration of CDDP.

PMID- 8858261
TI  - Vocal fold vibration in simulated head voice phonation in excised canine
      larynges.
AB  - In order to establish precise vibratory patterns and their clinical implication
      for phonation, the mode of vibration of the vocal folds around the time of
      register transition in excised canine larynges was analyzed multi-directionally
      according to various acoustic parameters. Phonation was simulated by artificially
      tensing the cricothyroid muscles. Vibration of the vocal folds around the time of
      register transition was filmed from above using ultra-high-speed cinematography
      and in a frontal plane using X-ray stroboscopy. Acoustic parameters included
      subglottic pressure, pitch, intensity and tension and were recorded
      simultaneously during register transition. The fundamental vibration patterns
      observed during vocal phonation were the same as that involved in chest voice
      phonation in excised canine larynges, with respect to the traveling wave of the
      vocal fold vibration. Changes in the physical properties of the vocal folds were
      considered to occur at register transition. These changes were probably strongly
      dependent upon changes in the structure of the lamina propria. Head voice
      phonation requires adaptability of the lamina propria and is less efficient than
      chest voice phonation. Hence, head voice phonation would be one method for
      assessing the condition of the vocal folds.

PMID- 8858262
TI  - Susceptibility of microorganisms isolated from chronic suppurative otitis media
      to ciprofloxacin.
AB  - In order to evaluate the susceptibility of the microorganisms isolated from
      chronic suppurative otitis media to ciprofloxacin, cultures of specimens from 127
      patients with chronic suppurative otitis media and their antibiotic sensitivity
      results were examined. The most common aerobic isolates were Pseudomonas sp.,
      Proteus sp., and Staphylococcus aureus with recovery rates of 40.7%, 21.6% and
      19.1% respectively. Sensitivity results showed that 6.2% of Pseudomonas isolates,
      2.9% of Proteus isolates, 10% of Staphylococcus aureus isolates and 8.3% of
      Escherichia coli isolates were resistant to ciprofloxacin.

PMID- 8858263
TI  - Effects of furosemide on intracochlear oxygen tension in the guinea pig.
AB  - The effects of intravenous furosemide on the perilymphatic oxygen tension of the
      scala tympani (OT) in the guinea pig and the relationship between changes in OT
      and changes in auditory cortical-evoked responses were studied, as well as
      changes in cochlear morphology. Furosemide in dosages of 25 mg/kg and 50 mg/kg
      caused a sharp decline in OT in addition to elevation of the threshold of
      auditory cortical-evoked responses. Ischemia of the cochlear stria vascularis was
      also found but without any damage of hair cells at the light microscopic level.
      Changes in OT were associated with transient threshold elevations and ischemia of
      the stria vascularis. Improvements in hearing were directly proportional to the
      recovery of OT.

PMID- 8858264
TI  - Apoptosis in the normal olfactory epithelium of the adult guinea pig.
AB  - Among nerve cells of vertebrates, the olfactory epithelia are uncommon in their
      capacity for cell turnover. Apoptosis is well known to play a key role in
      maintaining homeostasis in continuously renewing tissues. We examined whether
      true apoptosis occurred in the normal olfactory epithelia of healthy adult guinea
      pigs using nucleic acid labeling. Subsequently, apoptosis was recognized in
      olfactory nerve cells, indicating that apoptosis might play a role in turnover of
      the olfactory epithelium.

PMID- 8858265
TI  - Intracochlear schwannoma.
AB  - In the case reported evaluation of unilateral endocochlear deafness in a 44-year
      old man led to a diagnosis of a small intracanalicular neurinoma of the cochlear
      nerve which had invaded the first turn of the cochlear spiral.

PMID- 8858266
TI  - The incidence of laryngeal cancer by anatomical site in south-western Finland.

PMID- 8858267
TI  - Actinomycosis of the middle ear and mastoid.

PMID- 8858268
TI  - Adaptive changes in the acute haemodynamic effects of cilazapril during chronic
      treatment. Comparison with long-term clinical effect.
AB  - OBJECTIVE: To study the adaptive changes in the acute haemodynamic response to
      ACE inhibition during chronic treatment in CHF. METHODS: The acute and chronic
      effects of oral cilazapril (CLZ) treatment, an ACE-inhibitor with prolonged
      duration on haemodynamic measures (PCWP, PAP, RAP, CI and SVR) and clinical
      parameters (Quality-of-Life and NYHA class) were investigated in a double-blind,
      randomised, placebo-controlled trial in CHF. One hundred and thirty five patients
      (112 completing) in NYHA Classes II-III, on digitalis and diuretic treatment,
      were randomised after 2 weeks of placebo run-in, to receive either placebo or CLZ
      0.5 mg, 1.0 mg or 2.5 mg daily for 12 weeks, followed by 2 week placebo wash-out.
      Haemodynamic studies, including exercise tests before and 3 h after medication,
      were performed on the first and last days of treatment. Measurements were
      performed at rest and at the maximum exercise level. RESULTS: In ACEI-naive
      patients oral CLZ 0.5 and 1 mg/d caused a dose dependent decrease in PCWP and
      diastolic PAP, and a significant reduction of SVR mg. A slight increase in CI was
      observed in all groups. The maximum effect was observed 3-5 h post dose. After 12
      weeks of oral treatment, the acute response was similar but was attenuated
      relative to the first dose. Exercise tolerance improved in a dose dependent
      manner. The NYHA classification remained unchanged or improved in the majority of
      patients. Entry into the 2.5 mg group had to be terminated at an early stage due
      to severe adverse events observed after the first dose. CONCLUSION: During
      chronic treatment, the haemodynamic response to oral cilazapril was attenuated,
      indicating that continued clinical improvement in patients with CHF on CLZ is
      independent of to its acute haemodynamic effects.

PMID- 8858269
TI  - Leg oedema protection from a buckwheat herb tea in patients with chronic venous
      insufficiency: a single-centre, randomised, double-blind, placebo-controlled
      clinical trial.
AB  - OBJECTIVES: The efficacy of a buckwheat herb tea was determined in patients with
      chronic venous insufficiency (CVI) in a single-centre, randomised, double-blind,
      placebo-controlled clinical trial. METHODS: Sixty-seven male and female patients
      (22-74 years) with CVI were randomly divided into two groups after a 2-week run
      in period. They received either buckwheat herb tea (Fagopyrum esculentum) or a
      placebo tea for a period of 3 months. The main outcome measure was the lower leg
      volume determined by ultrasound. Subjective symptoms were assessed by a clinical
      symptom score system. The femoral vein diameters were measured by B-scan
      sonography. In a subgroup of patients capillary permeability was determined by
      cutaneous fluorescence angiography. RESULTS: Although the mean partial leg volume
      did not change in the treatment group (from 2041 to 2073 ml), it increased in the
      placebo group by 110 ml (from 1972 to 2082 ml) according to intent to treat. The
      difference between the groups was significant. The subjective clinical symptoms
      were significantly reduced in both groups. The mean diameters of the femoral
      veins were reduced and capillary permeability was improved, but neither change
      was statistically significant. No drug-related adverse effects were observed.
      CONCLUSION: CVI is a very placebo-sensitive condition. The treatment with
      buckwheat herb tea is safe and could have a favourable influence on patients with
      CVI such that further oedema development is prevented.

PMID- 8858270
TI  - Statistical interpretation of the antisecretory effect of famotidine measured by
      intragastric pH-metry.
AB  - OBJECTIVE: Intragastric pH-metry is widely used to evaluate the efficacy of
      antisecretory drugs, but statistical interpretation of the measurements has not
      yet been standardised. METHODS: The effects of single morning (N = 9) or evening
      (N = 7) doses of the H2-receptor antagonist famotidine, 20 mg (QUAMATELR. Gedeon
      Richter, Hungary) were compared by 24-hour intragastric pH-metry in hyperacid
      patients, in a prospective, controlled clinicopharmacological study. Intragastric
      pH was repeatedly measured with or without administration of famotidine, and ?1?
      the minute to minute median pH values were calculated. RESULTS: ?2? Both
      treatments significantly reduced gastric acidity according to the "traditional"
      parameters of the time at pH > or = 3, or median pH in the first 12 hours.
      Famotidine treatment in the evening was more effective than in the morning (634
      vs 463 min or 5.22 vs 3.10). The morning and evening treatment groups did not
      differ from each other in these parameters when compared on the days without
      famotidine. ?3? After demonstration of the significant differences between the
      treatment vs control days, and morning vs evening administrations we applied the
      Pattern Recognition by Independent Multicategory Analysis (PRIMA) method to
      select the most sensitive parameters for evaluation of the H2-receptor antagonist
      drug effect. The PRIMA method was developed to determine the sensitivity of each
      statistical parameter analysed in a comparison of different groups
      (discriminating power), and to determine the separability of groups using several
      parameters concomitantly (separation of groups). The mean pH, the period at pH >
      or = 3, and the duration of pH-increase > or = 1 on the day of treatment compared
      to the control day were found to be the most sensitive parameters both in
      demonstrating H2-receptor antagonist effect and in differentiation of morning and
      evening doses. ?4? High separability of morning and evening treatment groups was
      achieved using these three parameters concomitantly according to the PRIMA
      method. CONCLUSION: This method may be of value in other clinical or
      clinicopharmacological trials to standardise the statistical analysis of data by
      selection of the most sensitive parameters for comparison of the patient groups.
      In subsequent studies it might also increase the sensitivity of discrimination by
      concomitant analysis of different parameters using the smallest appropriate
      number of patients.

PMID- 8858271
TI  - Effect of N-acetylcysteine(NAC) treatment on HIV-1 infection: a double-blind
      placebo-controlled trial.
AB  - OBJECTIVE: In a double-blind placebo-controlled trial, human immunodeficiency
      virus (HIV)-seropositive patients with a CD4 lymphocyte cell count of more than
      200 x 10(6) . l-1 were randomised to receive either 800 mg N-acetylcysteine (NAC)
      or placebo for 4 months. Before treatment low plasma cysteine levels, high free
      radical activity in neutrophils in the presence of autologous plasma-measured by
      the nitroblue tetrazolium (NBT) test- and increased tumor necrosis factor (TNF)
      alpha levels were found in the HIV positive patients. RESULTS: After treatment
      the low plasma cysteine level in the NAC group increased to normal, and the
      decline of the CD4+ lymphocyte count before the study start, was less steep in
      the NAC group than in the placebo group after treatment. There was also a
      reduction in TNF-alpha level. However, NAC had no effect on the radical
      production by neutrophils, and although it did not increase the CD4+ cell count,
      it may have decreased the decline in CD4+ cells. CONCLUSION: Further controlled
      trials with NAC are needed to determine whether it has a beneficial effect in the
      treatment of asymptomatic HIV-infected individuals.

PMID- 8858272
TI  - Effect of clonidine and yohimbine on sleep in healthy men: a double-blind,
      randomized, controlled trial.
AB  - OBJECTIVE: To study the acute effect of clonidine, an alpha 2-adrenoceptor
      agonist, and yohimbine, an alpha 2-adrenoceptor antagonist, on nocturnal sleep in
      healthy men. SETTING: McGuire Veteran Affairs Medical Center, Richmond, Virginia,
      USA. SUBJECTS: Eight healthy male volunteers. METHODS: Each subject slept in the
      sleep laboratory for 2 consecutive nights on three separate sessions, at 3-week
      intervals. On the 2nd night of each session, the subjects received yohimbine (5.4
      mg), clonidine (0.1 mg), or placebo in a double-blind, randomized, placebo
      controlled, crossover design. RESULTS: There were no apparent effects of
      yohimbine. In contrast, clonidine completely suppressed rapid eye movement (REM)
      sleep in one subject and reduced REM sleep in the remaining seven subjects.
      CONCLUSION: Our study confirms that clonidine markedly decreases REM, even at a
      low single dose, and supports the hypothesis of the important role of alpha 2
      receptors in controlling REM sleep.

PMID- 8858273
TI  - Relative efficacy of three different inhalers containing salbutamol in patients
      with asthma.
AB  - OBJECTIVE: To investigate the relative efficacy of three inhalers containing
      salbutamol: Turbuhaler (TBH), Rotahaler (RH) and Diskhaler (DH). METHODS: A
      randomized, open, three-way crossover, cumulative dose response study was
      performed in 20 patients with asthma with mean forced expiratory volume in ls
      (FEV1) values of 60% of predicted (range 41-90%) and a 27% reversibility in FEV1
      (range 15-61%). Four doses of salbutamol were inhaled at 30-min intervals: 50
      micrograms, 50 micrograms, 100 micrograms and 200 micrograms by TBH and 200
      micrograms, 200 micrograms, 400 micrograms and 800 micrograms by both RH and DH.
      FEV1 was measured at baseline and 25 min after each dose. RESULTS: The increases
      in FEV1 after the first doses (50 micrograms by TBH, 200 micrograms by RH and by
      DH) were not statistically significantly different (23.6%, 25.1% and 28%,
      respectively). Based on the parallel shift in the dose response curves,
      salbutamol TBH was calculated to be 2.4 times as potent as salbutamol RH (95%
      confidence interval 1.4-3.3) and 2.2 times as potent as salbutamol DH (90% CI 1.3
      3.3). Additionally, during dosing with TBH, fewer patients experienced adverse
      events than during dosing with RH or DH. CONCLUSION: Turbuhaler is a twofold more
      efficient inhaler for salbutamol than Rotahaler or Diskhaler as measured by its
      bronchodilating effect.

PMID- 8858274
TI  - Oculo-bulbar myasthenia gravis induced by cytokine treatment of a patient with
      metastasized renal cell carcinoma.
AB  - OBJECTIVE: The occurrence of autoimmune diseases or deterioration of pre-existing
      disorders has recently been described after cytokine treatment. The present
      report gives evidence for acquired myasthenia gravis induced by externally
      administered interferon-alpha and interleukin-2 in a patient with metastasized
      renal cell carcinoma. Electromyographic investigations did not reveal generalised
      myasthenia gravis. However, a highly elevated titre of antibodies against the
      human acetylcholine receptor and a significant improvement in clinical symptoms
      during therapy with anticholinesterase drugs, combined with a decremental
      response in electronystagmography, indicated an intermittent mainly oculo-bulbar
      form of myasthenia gravis.

PMID- 8858275
TI  - Effects of mefloquine alone and with alcohol on psychomotor and driving
      performance.
AB  - OBJECTIVE: To determine whether mefloquine, a quinoline antimalarial drug,
      affects psychomotor and actual driving performance when given in prophylactic
      regimen, alone or in combination with alcohol. METHODS: Forty male and female
      volunteers were randomly assigned in equal numbers to two groups, and were
      treated double-blind for one month with mefloquine and placebo. The medication
      was taken in a 250 mg dose on the evenings of Days 1, 2, 3, 8, 15, 22 and 29.
      Testing was done on Days 4, 23 and 30, the latter after repeated doses of alcohol
      sufficient to sustain a blood concentration of about 0.35 mg.ml-1. Two real
      driving tests were used to measure prolonged (1 h) road tracking and car
      following performance. Critical Flicker/Fusion Frequency (CFF), critical
      instability tracking and body sway were also measured in the laboratory. RESULTS:
      Mefloquine caused no significant impairment in any test at any time relative to
      placebo. It significantly improved road tracking performance on Day 4. A
      significant interaction between prior treatment and alcohol was found in the body
      sway test, as the alcohol-induced change was less after mefloquine than placebo.
      The sensitivity of the driving test and the CFF test were shown by the
      significant overall effect of alcohol which did not discriminate between the two
      prior treatments. CONCLUSION: Mefloquine did not impair driving performance but
      rather improved it in the longer test, suggesting that the drug may possess
      psychostimulating properties.

PMID- 8858276
TI  - Effects of carvedilol and atenolol on arterial pulse curves (plethysmography) and
      finger temperature after hand cooling.
AB  - OBJECTIVE: In a double-blind, parallel study, the effects of 25 mg carvedilol and
      50 mg atenolol on peripheral finger circulation and arterial pulse curve
      configuration were compared. METHODS: Healthy volunteers (n = 17) were examined
      at baseline and for 15 min after 60 s of hand cooling in ice-water. Finger
      temperature and digital plethysmography were recorded each minute from the cooled
      and the control hands. Measurements were also made before and 2 h after drug
      administration. RESULTS: Blood pressure declined from 120/86 to 108/74 mm Hg
      after atenolol (n = 9), and from 122/88 to 108/73 mm Hg after carvedilol (n = 8).
      In both groups, baseline finger temperature increased slightly after drug, and a
      more rapid rise in finger temperature was observed after cooling. There was no
      group difference in the drug effect on finger temperature, except in the first
      few minutes after cooling, when temperature recovery was greater after
      carvedilol. Carvedilol reduced the vasoconstrictor response to local cooling
      (digital plethysmography), compared both to the value before drug and after
      atenolol. At rest, carvedilol changed the pulse curves (control hand) towards
      vasodilatation and high compliance, expressed as a mean change in the relative
      height of the dicrotic notch of -10.3% versus 0.0% after atenolol. CONCLUSION:
      Future studies should clarify whether the vasoactive profile of carvedilol may
      translate into reduced occurrence of cold hands and feet amongst patients treated
      for hypertension.

PMID- 8858277
TI  - Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor
      (aprotinin) from the small intestine in healthy volunteers.
AB  - OBJECTIVE: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine
      vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six
      healthy, male volunteers aged 19-34 years, followed for 8 h after each drug
      administration. METHODS: For i.v. administration the subjects received 4
      micrograms dDAVP. For intestinal administration 500 micrograms dDAVP was
      administered directly, in two separate sessions, in the first part of the
      duodenum via a triple-lumen channel tube. In one session a solution of isotonic
      polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the
      other session a solution of PEG and aprotinin was administered enterally at the
      constant rate of 5 ml.min-1 for 4 h. Plasma dDAVP was measured using a specific,
      sensitive radioimmunoassay and intestinal juice was collected for measurement of
      lipase, chymotrypsin and pH every 30 min for 5 h. RESULTS: The intestinal
      chymotrypsin activity was decreased after perfusion of aprotinin while the lipase
      activity was not modified. After i.v. administration, the half-life of
      elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml.min.kg-1. The mean
      bioavailability after duodenal administration of dDAVP+ aprotinin was 0.46%
      compared with 0.09% after duodenal administration of dDAVP alone. The
      bioavailability of dDAVP after direct duodenal administration of an aqueous
      solution was similar to that after swallowing a tablet in a previous study and
      increased 5 times when given together with a perfusion of an enzyme inhibitor.

PMID- 8858278
TI  - Effect of stiripentol on carbamazepine plasma concentration and metabolism in
      epileptic children.
AB  - OBJECTIVE: To study the relationship between the plasma concentration of
      stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the
      formation of carbamazepine epoxide (CBZE) in epileptic children treated with
      carbamazepine (CBZ) either alone or in combination with another antiepileptic
      drug. METHODS: Minimum plasma concentration of antiepileptic drugs was measured
      before initiation of STP therapy (day 0) and on days 28 (STP 60 mg.kg-1.day-1)
      and 84 (STP 90 mg.kg-1.day-1) by HPLC. RESULTS: The CBZE/CBZ plasma concentration
      ratio decreased exponentially with increasing minimum plasma STP concentration (r
      = 0.80). The asymptote of the curve allowed the calculation of the minimum plasma
      STP concentration required to obtain the maximum inhibitory effect, i.e. 6.7 mg.l
      1. CONCLUSION: The inhibitory effect of STP on CBZ metabolism expressed as the
      CBZE/CBZ plasma concentration ratio is dependent on STP plasma concentration,
      with a maximum effect at an average of 7 mg.l-1. The present data suggest that in
      order to evaluate the anticonvulsant efficacy of STP as add-on therapy, the
      minimum plasma STP concentration should be maintained above 7 mg.l-1 and the
      dosage of CBZ should simultaneously be decreased in steps by more than 50% to
      minimize the change in CBZ plasma concentration.

PMID- 8858279
TI  - Grapefruit juice does not enhance the effects of midazolam and triazolam in man.
AB  - OBJECTIVES: Since grapefruit juice (Gra) inhibits hepatic P450 (CYP3A4), we
      studied its potential to enhance the effects of midazolam (Mid) and triazolam
      (Trz), which are metabolized by the CYP3A4 isoenzyme. METHODS: In Study I
      parallel groups of healthy students were given orally Mid 10 mg with water or
      grapefruit juice (GraMid), two placebo groups receiving water or Gra. The effects
      of Mid were measured by psychomotor tests and by self-rating on visual analogue
      scales before and 30 and 90 min after intake. Study II was similar, but the post
      treatment tests were at 45 and 90 min, and the active drugs used were 0.250 mg
      Trz, GraTrz, and Mid 10 mg. In the crossover Study III, 6 subjects took Mid 10 mg
      alone and with Gra (GraMid) and 750 mg erythromycin (EryMid). Performance tests
      were made and blood was sampled before and 30, 60 and 90 min after intake.
      Midazolam and its active metabolite alpha-OH-midazolam were assayed by gas
      chromatography (GC) and radioreceptor assay (RRA). RESULTS: In Study I, both Mid
      and GraMid impaired digit symbol substitution (DSS), letter cancellation (LC) and
      flicker fusion (CFF) at 90 min. GraMid had more effect (P < 0.05) than Mid on the
      DSS performance. Mid caused drowsiness at 30 and 90 min. Both Mid and GraMid
      caused clumsiness and a feeling of impaired performance at 90 min. In Study II,
      the active drugs impaired objective test performances (DSS, LC, CFF) at 90 min,
      without having a clear subjective effect. In Study III, Mid, EryMid and GraMid
      impaired performance in the DSS, LC and CFF tests. EryMid proved stronger than
      Mid and GraMid on DSS and LC tests at 30 min. Mean values of plasma midazolam
      (and alpha-OH-midazolam) at 30, 60, 90 and 120 min after Mid 10 mg were 68(19),
      61(19), 43(14) and 42(12) micrograms.l-1. The corresponding values after EryMid
      were 164(14), 137(13), 104(10) and 89(10) micrograms.l-1, and after GraMid
      60(12), 69(16), 61(15) and 57 (14) micrograms.l-1. CONCLUSIONS: The grapefruit
      juice used did have any particular interaction with oral doses of 10 mg midazolam
      and 0.25 mg triazolam in healthy young subjects.

PMID- 8858280
TI  - Amnestic syndrome induced by zoplclone.

PMID- 8858281
TI  - Bioavailability of ciprofloxacin in patients with acute infectious diarrhoe.

PMID- 8858282
TI  - Influence of food intake on the bioavailability of thioctic acid enantiomers.

PMID- 8858283
TI  - HLA-A2 polymorphism and immune functions.

PMID- 8858284
TI  - Immunogenetic factors in HPV-associated cervical cancer: influence on disease
      progression.
AB  - No HLA allele or specificity was significantly different in frequency between a
      group of 150 cervical cancer patients from north-west England and controls
      (corrected P values). HLA-DRB1*1501/DQB1*0602 was non-significantly increased,
      particularly among patients with HPV16-positive tumours. HLA-B7-positive patients
      had a significantly poorer clinical outcome than HLA-B7-negative patients. A
      significant component of the genotypic effect is down-regulation of HLA-B7
      expression by the tumour cells.

PMID- 8858285
TI  - HLA class II region genes and susceptibility to dermatitis herpetiformis: DPB1
      and TAP2 associations are secondary to those of the DQ subregion.
AB  - Classical dermatitis herpetiformis (DH) is associated with similar HLA class I,
      II and III polymorphisms to coeliac disease (CD). The two diseases share
      distinctive pathological changes to the small intestinal mucosa which reverse on
      withdrawal of dietary gluten. In order to determine the locus primarily
      associated with DH, and to examine whether there is a common genetic link
      predisposing to the enteropathy seen in both DH and coeliac disease, HLA-DR, DQ
      and DP subregion associations were investigated by HLA genotyping in 23 DH
      patients and 64 healthy controls. We also studied polymorphisms of the TAP2
      locus, which is located between the DP and DQ subregions. Genotyping was carried
      out by PCR of genomic DNA with allelic assignment by sequence-specific
      oligonucleotide (SSO) hybridization or amplification refractory mutation system
      (ARMS). The strongest associations in the patient group were with HLA DRB1*0301
      (91% vs 22% of controls), HLA DQB1*02 (100% vs 32% of controls) and DPB1*0101
      (39% and 14%). These associations are similar to those described for CD. 100% of
      DH patients were positive for the DQA1*0501/DQB1*02 dimer in cis or trans and, by
      analogy with CD, this is probably responsible for presenting gliadin peptide
      implicated in the disease process. Homozygosity for DQ2 was significantly
      increased in the CD patient group compared to the DH patient group (65% versus
      39%), and so differences in dosage of HLA class II genotypes between DH and CD
      may be responsible for the milder gastrointestinal symptoms characteristic of DH.

PMID- 8858286
TI  - Long-range PCR amplification as an alternative strategy for characterizing novel
      HLA-B alleles.
AB  - We have developed a simple, rapid and reliable method for specifically amplifying
      and cloning full-length HLA-B genes from genomic DNA. Using this methodology we
      characterized three alleles of interest at the molecular level. Two of the
      alleles appeared in our routine class I PCR-SSOP typing system, a variant of
      B*5801 found in the Daudi cell line and RCE 56 and a variant of B*4101 found in a
      number of volunteer donors on our Bone Marrow Donor Registry. The third, a
      variant B35 allele found in RCE 80, was first identified as unusual by serology.
      Our sequencing analysis of exon 2 and exon 3 identified two of these alleles as
      the recently reported novel HLA-B*5802 and HLA-B*4102 alleles, while the third
      represents a new B35 allele officially designated B*3513.

PMID- 8858287
TI  - Distribution of HLA-G alternative mRNAs including soluble forms in normal
      lymphocytes and in lymphoid cell-derived leukemia.
AB  - The non-classical HLA-G gene is the only class I antigen expressed in
      trophoblasts at the maternofetal interface. In placenta, the HLA-G gene produces
      several alternatively spliced isoforms encoding bound-membrane proteins (G1, G2,
      G3 and G4) lacking, respectively, exon 7; exons 7 and 3; exons 7, 3 and 4, and
      exons 7 and 4. In addition, two isoforms (G1s and G2s) containing an intron 4
      sequence are able to encode soluble antigens. We have recently reported that the
      HLA-G gene is transcriptionally active in lymphocytes and is not transcribed in
      CD34+ cells, polynuclear cells or monocytes. To investigate the functional
      significance of the different isoforms in lymphocytes, we studied their
      distribution in normal T and B lymphocytes and in malignant lymphoid cells by
      using the RT-PCR technique followed by hybridization with exon-specific probes
      and sequencing assays. In transcriptionally active lymphocytes, the HLA-G primary
      transcript is the major form and is differentially spliced in B and T
      lymphocytes: (i) G1s is found in several samples of T and B cells whereas G2s is
      only transcribed in T lymphocytes, (ii) the G4 isoform is never detected in B
      lymphocytes. In addition, we have shown that HLA-G is inactive in some samples of
      lymphocytes. Our data suggest that HLA-G transcription is regulated at the
      initiation level and at the subsequent splicing. These two levels of regulation
      may be dysregulated in some cases of T-ALL and CLL. The potential functions of
      the HLA-G alternative forms in lymphocytes, such as peptide binding and
      modulation of the immune response, are discussed.

PMID- 8858288
TI  - HLA five-locus haplotypes in Finns.
AB  - The extreme polymorphism of HLA genes makes them a powerful tool for
      distinguishing between different genetic populations. Five-locus HLA haplotypes
      of Finns (from Oulu, Northern Finland) are described here in order to
      characterize further the migration pathways of the population to Finland after
      the Ice Age. From random families, 364 haplotypes were obtained. The most
      frequent Finnish haplotype A3,Cw4,B35,DR1,DQ1 (7.7%) is a Caucasoid ancestral
      haplotype and is shared with Italians of Celtic and non-Celtic origin. The
      haplotype A1,Cw7,B8,DR3,DQ2, which occurs in 4.7% of Finns, is the most frequent
      haplotype in Caucasoids. The haplotypes A3,Cw7,B7,DR2,DQ1 (3.6%) and
      A2,Cw7,B7,DR2,DQ1 (2.5%) are shared with several Caucasoid populations and the
      latter also with Jamaican blacks. A2,Cw5,B44,DR5,DQ3 (0.8%) is shared with
      Italians of Celtic and non-Celtic origin, A2,Cw6,B13,DR7,DQ2 (1.1%) with
      Caucasoids in the USA and A9,Cw4,B35,DR1,DQ1 (0.8%) with Mongoloids. The
      haplotypes A2,CW3,B62,DR4,DQ3 (3.0%), A2,Cw2,B27,DR8,DQ4 (1.7%),
      A2,Cw3,B62,DR6,DQ1 (1.4%) and A2,Cw1,B27,DR4,DQ3 (1.4%) were also found to be
      among the most frequent in the Finnish population. The most frequent HLA
      haplotypes are consistent with the postulated ancient migration of populations
      from southern Scandinavia and Germany to Finland, the most frequent haplotype
      suggesting a common Celtic origin and one less frequent haplotype suggesting an
      influence from the east.

PMID- 8858289
TI  - Nomenclature for factors of the HLA system, update February 1996.

PMID- 8858290
TI  - Nomenclature for factors of the HLA system, update March 1996.

PMID- 8858291
TI  - Nomenclature for factors of the HLA system, update April 1996.

PMID- 8858292
TI  - Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2
      receptors in the shell of the nucleus accumbens; jaw movements.
AB  - The goal of this study was to determine whether the dopamine D3 receptor in
      limbic structures plays a role in the shell-specific and dopamine-dependent
      display of jaw movements in rats. When combined with the dopamine D1 receptor
      agonist (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1- phenyl-2,3,4,5-tetrahydro-1 H-3
      benzazepine (SKF 82958, 5 micrograms), the putative dopamine D3 receptor agonist
      (+/-)-7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 10 micrograms)
      produced repetitive jaw movements following injection into the shell, but not the
      core, of the nucleus accumbens. This behaviour was only partially inhibited by
      local blockade of dopamine D1 receptors (R(+)-7-chloro-8-hydroxy-3-methyl-1
      phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390, 500 ng), dopamine D2
      receptors (domperidone, 50 and 100 ng) or dopamine D2/3 receptors (l-sulpiride,
      25 ng). Combined blockade of both dopamine D1 and D2 receptors in the shell
      completely antagonized the jaw movements elicited by the cocktail of SKF 82958
      and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor
      agonist, S(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[I]benzopyrano[4,
      3-b]-1, 4-oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did not
      produce jaw movements, when administered into the shell. Injection of the
      cocktail of SKF 82958 and 7-OH-DPAT into the ventrolateral striatum, which
      contains nearly no dopamine D3 receptors, also elicited jaw movements. It is
      concluded that mesolimbic dopamine D3 receptors play no role in the dopamine
      dependent and shell-specific jaw movements: the contribution of 7-OH-DPAT in the
      cocktail of SKF 82958 and 7-OH-DPAT to the display of jaw movements is solely due
      to its ability to activate dopamine D2 receptors.

PMID- 8858293
TI  - Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2
      receptors in the shell of the nucleus accumbens; turning behaviour.
AB  - The goal of this study was to determine whether the dopamine D3 receptor in
      limbic structures plays a role in the shell-specific and dopamine-dependent
      display of turning behaviour in rats. When combined with the dopamine D1 receptor
      agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7,8-diol (SKF-38393,
      5 micrograms), the putative dopamine D3 receptor agonist (+/-)-7-hydroxy-N,N-di-n
      propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 micrograms) elicited contralateral
      turning in a dose-dependent manner following unilateral injection into the shell,
      but not the core, of the nucleus accumbens. The turning pattern displayed was
      identical to that reported previously after intra-accumbens administration of the
      cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The
      behaviour under study was dose-dependently attenuated by local administration of
      the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3- methyl-I-phroyl
      2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390: 10 and 100 ng), the dopamine D2
      receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor
      antagonist l-sulpiride (5 and 25 ng). Combined blockade of both dopamine D1 and
      D2 receptors in the shell with a dose of either antagonist alone that produced
      just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely
      antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH
      DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist,S(+)
      (4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4, 3-b]-1, 4
      oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did produce no turning
      behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no
      role in the dopamine-dependent and shell-specific turning behaviour: the
      contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the
      display of turning behaviour is solely due to its ability to activate dopamine D2
      receptors.

PMID- 8858294
TI  - Depletion of serotonin, dopamine and noradrenaline in aged rats decreases the
      therapeutic effect of nicotine, but not of tetrahydroaminoacridine.
AB  - The present study investigates the effects of nicotine (0.1 and 0.3 mg/kg) and
      tetrahydroaminoacridine (3 mg/kg) treatment on spatial navigation in aged control
      and p-chlorophenylalanine (a serotonin (5-hydroxytryptamine, 5-HT) synthesis
      inhibitor, 400 mg/kg on 3 successive days, i.p.)-treated rats. p
      Chlorophenylalanine did not aggravate the water maze failure of aged rats.
      Nicotine (0.3 mg/kg) was more effective than tetrahydroaminoacridine (3 mg/kg) in
      promoting water maze navigation by aged control rats. p-Chlorophenylalanine
      blocked the therapeutic effect of nicotine (0.3 mg/kg),but did not decrease the
      effect of tetrahydroaminoacridine (3 mg/kg) in aged rats. Frontal cortex dopamine
      levels and choline acetyltransferase activity were lower in aged rats, but 5-HT
      and noradrenaline levels were unaltered. p-Chlorophenylalanine decreased
      selectively 5-HT levels in young rats, but in aged rats 5-HT, dopamine and
      noradrenaline levels were decreased. These results suggest that aged rats are
      neurochemically more sensitive to p-chlorophenylalanine treatment and that
      tetrahydroaminoacridine may more effectively than nicotine stimulate spatial
      learning if 5-HT, dopamine and noradrenaline systems are severely affected.

PMID- 8858295
TI  - Antinociceptive effects of oral clonidine and S12813-4 in acute colon
      inflammation in rats.
AB  - Acute colonic inflammation was induced by perendoscopic injection of 50
      microleters of dilute formalin (5%) in the depth of the colonic wall (c.w.) in
      rats. Compared to saline injection, the procedure was followed by nociceptive
      behaviors from which visceral nociception was quantified. The alpha 2
      adrenoceptor agonist, clonidine 2-[2,6-dichlorophenylamine]-2-imidazole
      hydrochloride (75, 150 and 300 mg/kg), administered orally 15 min after c.w.
      injection of formalin significantly reduced the nociceptive responses at the high
      dose only. However, when administered 30 min prior to nociceptive stimulation,
      the compound exhibited an antinociceptive effect at the three doses. A novel
      analgesic, the compound "S12813-4' 3-[2-(4-phenylpiperazine-1-yl)-ethyl]-2-oxo
      2,3-dihydro-oxazolo[b] pyridine, chlorydrate (10, 30 and 90 mg/kg), given orally
      displayed antinociceptive effects whatever the administration schedule, before or
      after c.w. injection of formalin. The antinociceptive effect of S12813-4 (30
      mg/kg given orally) was prevented by subcutaneous (s.c.) injection of yohimbine
      or idazoxan (1 mg/kg). We conclude that visceral nociception elicited by formalin
      induced colonic inflammation is attenuated by clonidine and S12813-4. The
      pharmacological profiles of the two compounds and the inhibition of the
      antinociceptive effect of S12813-4 by yohimbine and idazoxan suggest that
      noradrenergic mechanisms are involved in the transmission and/or modulation of
      the nociceptive influx arising from the inflamed colon.

PMID- 8858296
TI  - In vivo evidence for preferential role of dopamine D3 receptor in the presynaptic
      regulation of dopamine release but not synthesis.
AB  - Brain microdialysis was used to investigate the effects of the putative dopamine
      D3 receptor agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT)
      on dopamine release, metabolism and synthesis in the dorsal striatum and nucleus
      accumbens of awake rats. The drug administered i.p. dose dependently decreased
      the release, metabolism and synthesis of dopamine in both brain areas. The
      potency of 7-OH-DPAT to decrease dopamine release was found to be higher in the
      nucleus accumbens than in the dorsal striatum (ED50 for nucleus accumbens 0.0096
      mg/kg, i.p.; for dorsal striatum 0.068 mg/kg, i.p.). Dopamine metabolism,
      assessed by measuring 3,4-dihydroxyphenylacetic acid extracellular levels, and
      dopamine synthesis, determined as 3,4-dihydroxyphenylalanine output following
      perfusion with the L-aromatic acid decarboxylase inhibitor 3
      hydroxybenzylhydrazine (10(-5) M), were decreased at higher dose ranges of 7-OH
      DPAT (ED50 for decrease of 3,4-dihydroxyphenylalanine output in nucleus accumbens
      0.124 mg/kg, i.p.; in dorsal striatum 0.101 mg/kg, i.p.). The hypomotility of
      rats induced by 7-OH-DPAT in doses of 0.002-0.25 mg/kg, i.p., was shown to
      correlate with the decreased dopamine release in the nucleus accumbens.
      Pretreatment of animals with 7-OH-DPAT at the putative dopamine D3 receptor
      'selective' dose of 0.05 mg/kg, i.p., was found to prevent the increase of
      dopamine release but not the increase in metabolism in the dorsal striatum of
      freely moving rats induced by (+)-AJ76, cis (+)-(1S,2R)-5-methoxy-1-methyl-1-2-(n
      propylamino)tetralin HCI (7 mg/kg, i.p.) and haloperidol (0.1 mg/kg, i.p.). Local
      application of 7-OH-DPAT by addition into the perfusing medium also resulted in a
      preferential decrease of dopamine release in the nucleus accumbens as compared
      with the dorsal striatum (EC50 for nucleus accumbens 1.9 nM; for dorsal striatum
      11.3 nM). The present results give further support to the hypothesis that the
      dopamine D3 autoreceptor is preferentially involved in the presynaptic regulation
      of dopamine release, while the D2 autoreceptor controls dopamine synthesis.

PMID- 8858297
TI  - Involvement of locus coeruleus projections in opiate withdrawal but not in opiate
      tolerance in mice.
AB  - The ability of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a potent and
      selective noradrenergic neurotoxic compound, to modify morphine tolerance and
      dependence was investigated in mice DSP-4 pretreatment, either 50 or 100 mg/kg
      i.p., had no effect on the development of tolerance to the analgesic effect of
      morphine evaluated by the tail-flick test. On the contrary, the higher dose of
      DSP-4 prevented repetitive vertical jumping, a major naloxone-precipitated
      withdrawal symptom in mice. These results demonstrate that coerulean neuronal
      projections are not necessary for the development of tolerance but are clearly
      involved in the expression of withdrawal-induced jumping in mice.

PMID- 8858298
TI  - Effect of caffeine coadministration and of nitric oxide synthesis inhibition on
      the antinociceptive action of ketorolac.
AB  - The effects of caffeine and nitric oxide synthesis inhibition on the
      antinociceptive action of ketorolac were assessed using the pain-induced
      functional impairment model in the rat. Nociception was induced by the intra
      articular injection of uric acid. Ketorolac, but not caffeine, produced an
      antinociceptive effect which was reduced by NG nitro-L-arginine methyl ester (L
      NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration
      potentiated the ketorolac effect. L-NAME induced a dose-dependent reduction of
      this potentiation. The results suggest the participation of the L-arginine-nitric
      oxide-cyclic GMP pathway in the caffeine potentiation of ketorolac-induced
      antinociception.

PMID- 8858299
TI  - Duration-dependent increase in striatal glutamate following prolonged
      fluphenazine administration in rats.
AB  - Chronic neuroleptic administration has been shown to selectively increase
      striatal extracellular glutamate concentration. In the current study, age-matched
      female rats were administered chronic oral fluphenazime or no drug via their
      drinking water for 3 or 32 weeks. Microdialysis probes were inserted into the
      ventrolateral caudate putamen and the medial nucleus accumbens and dialysis
      samples were analyzed for glutamate and gamma-aminobutyric acid (GABA)
      concentrations Glutamate levels were significantly increased only in the
      ventrolateral caudate putamen after 32 weeks. No significant effects were seen
      for GABA levels. Neuroleptic-induced enhancement of striatal glutamate levels
      thus appears to increase with chronic exposure and this increase may relate to
      late onset motor side effects.

PMID- 8858300
TI  - Dopamine D3 receptor density elevation in aged Fischer-344 x Brown-Norway (F1)
      rats.
AB  - The density of dopamine D3 receptors was determined in young (4-month-old) and
      aged (37-month-old) Fischer-344 x Brown-Norway (F1) male rats using the putative
      D3 receptor-preferring agonist, [3H](+)-7.hydroxy-2-(N,N-di-n
      propylamino)tetralin ([3H](+)-7-OH-DPAT). In the presence of the non-hydrolyzable
      GTP analog, 5'-guanylylimidodiphosphate (Gpp(NH)p), the density of dopamine D3
      receptors in the striatum and nucleus accumbens was significantly increased (29
      102%, respectively) in aged Fischer-344 x Brown-Norway (F1) rats compared to
      young adults. These findings suggest that dopaminergic activity in aged rats is
      compromised by increased D3 receptor density, resulting in altered
      striatal/nucleus accumbens function via presynaptic or postsynaptic
      modifications.

PMID- 8858301
TI  - Pharmacological evidence of a role for platelet activating factor as a modulator
      of vasomotor tone and blood pressure.
AB  - The purpose of the present study was to investigate the role of platelet
      activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine),
      a phospholipid mediator synthesized by endothelial and smooth muscle cells, in
      the modulation of vascular tone and blood pressure. In pentobarbitone
      anaesthetised rabbits, unloading of the carotid sinus baroreceptors by a
      bilateral carotid artery occlusion elicited a reflex rise in arterial pressure
      which was markedly potentiated by pretreating the animals with the PAF receptor
      antagonists WEB 2086 [3-4-(2-chlorphenyl)-9-methyl-6H-thieno-3,2f-1,2,4-triazolo
      4, 3 a-1,4-diazepin-2-yl-(4-morpholinyl)-I-propanone; 2, 5 or 10 mg kg-1, i.v.]
      or BN 52021 (ginkgolide B; 0.1, 0.3 or 1.0 mg kg-1, i.v.). The increases in
      systemic vascular resistance induced by noradrenaline (30 micrograms kg-1, i.v.)
      or by the central activation of the sympathetic nervous system with glutamate (1
      mg kg-1, intracerebroventricular) were also significantly potentiated in animals
      pretreated with WEB 2086 (5 mg kg-1, i.v.). In contrast, pretreatment with the
      cyclooxygenase inhibitor indomethacin (3 mg kg-1, i.v.) did not affect the
      haemodynamic actions of noradrenaline, thus excluding the possibility that
      prostacyclin may modulate the potentiating effect. To further confirm that PAF is
      released during systemic vasoconstriction, the cardiovascular PAF receptors were
      desensitized by the daily administration of PAF (3 micrograms kg-1, i.v.) for
      seven days. This procedure significantly reduced the intensity and duration of
      the hypotensive response to a subsequent PAF injection (3 micrograms kg-1, i.v.).
      In desensitized animals, the hypertensive response to bilateral carotid artery
      occlusion was potentiated to the same extent as in the animals treated with PAF
      receptor antagonists. Inhibition of PAF biosynthesis by pretreatment of the
      animals with the phospholipase A2 inhibitor mepacrine (5 mg kg-1, i.v.) also
      enhanced the increase in blood pressure elicited by carotid artery occlusion. We
      conclude that PAF is involved in the acute but not basal modulation of vasomotor
      tone and, hence, arterial pressure, probably by a negative feedback mechanism
      triggered by important increases in the vascular tone.

PMID- 8858302
TI  - Stretch-induced increase in atrial natriuretic peptide secretion is blocked by
      thapsigargin.
AB  - The cellular mechanisms by which mechanical forces regulate myocardial function
      such as secretion of atrial natriuretic peptide (ANP), are uncertain. We studied
      the effects of thapsigargin, a specific inhibitor of sarcoplasmic reticulum Ca2+
      adenosine triphosphatase, that depletes intracellular Ca2+ stores, on basal and
      atrial stretch-induced ANP secretion in the isolated, perfused, paced rat heart
      preparation. Addition of 300 nM thapsigargin into the perfusate caused gradual
      increase in perfusion pressure, contractile force and ANP release (P < 0.001).
      Thapsigargin pretreatment at concentrations (30 and 100 nM) that did not affect
      baseline cardiac function or hormone secretion blocked mechanical stretch-induced
      increase in ANP secretion. These results suggest that thapsigargin-sensitive
      intracellular Ca2+ pools serve as mechanotransducers in the mechanical loading
      induced changes in cardiac myocytes.

PMID- 8858303
TI  - Agmatine is not a good candidate as endogenous ligand for imidazoline sites of
      pancreatic B cells and vascular bed.
AB  - In order to determine whether agmatine could be a putative endogenous ligand for
      imidazoline receptors mediating insulin secretion and vasoconstriction, we
      compared its effects with those of the imidazoline, efaroxan. Agmatine exhibited
      a much lower potency and efficacy than efaroxan on insulin secretion from rat
      pancreas perfused with 8.3 mM glucose. On the other hand, in contrast to efaroxan
      (100 microM), agmatine (3 mM) did not increase arginine-induced insulin release.
      In addition, agmatine failed to reproduce the vasoconstrictor effect of efaroxan
      on pancreatic vessels. These results show that agmatine does not behave like
      efaroxan, an agonist for the imidazoline receptors mediating insulin secretion or
      vasoconstriction in the pancreas.

PMID- 8858304
TI  - Relaxant effects of 17 beta-estradiol in the rat tail artery are greater in
      females than males.
AB  - To investigate whether sex differences contribute to the variability reported for
      acute effects of 17 beta-estradiol on vascular reactivity, the response to 17
      beta-estradiol was compared in male and female isolated perfused rat tail
      arteries. 17 beta-Estradiol (10(-7)-10(-5) M) attenuated the contractile response
      to norepinephrine in female, but not male, arteries, but had no effect when the
      endothelium was removed. Relaxation to 17 beta-estradiol reached a steady state
      within approximately 15 min. This hormone appears to acutely relax pre-contracted
      arteries from females but not males by a non-genomic effect requiring an intact
      endothelium.

PMID- 8858305
TI  - Hemodynamic effects and histamine release elicited by the selective adenosine A3
      receptor agonist 2-Cl-IB-MECA in conscious rats.
AB  - The hemodynamic effects of the novel, selective adenosine A3 receptor agonist 2
      chloro-N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IB-MECA) were
      investigated in conscious rats. Intravenous administration of 200 micrograms/kg 2
      Cl-IB-MECA resulted in a short-lasting hypotension, which was accompanied by a 50
      100-fold increase in plasma histamine concentrations. Administration of a second
      dose of 2-Cl-IB-MECA did not elicit any hemodynamic effects. Also no histamine
      release was observed after the second dose. The observation of rapid
      tachyphylaxis in combination with histamine release suggests that mast cell
      mediator release plays a key role in the hemodynamic effects of adenosine A3
      receptor agonists.

PMID- 8858306
TI  - Pharmacological characterization of 5-hydroxytryptamine-induced motor activity
      (in vitro) in the guinea pig gastric antrum and corpus.
AB  - In order to characterize the receptor subtypes involved in 5-hydroxytryptamine (5
      HT)-induced circular muscle motor responses of the guinea pig gastric antrum and
      corpus, we examined the effects of several antagonists in vitro. 5-HT evoked
      concentration-dependent contractions of the gastric antrum and relaxations of the
      corpus. 5-HT induced antral contractions were abolished by pretreatment with
      atropine and tetrodotoxin. Methysergide, ketanserin, granisetron and [1-[2
      (methylsulphonylamino)ethyl]-4-piperidinyl]methyl 1-methyl-1 H-indole-3
      carboxylate maleate salt (GRl13808A), but neither 1-(2-methoxyphenyl)-4-[4-(2
      phthalimido)butyl]piperazine (NAN-190) nor N2-[(4R)-4-hydroxy-1-(1-methyl-1 H
      indol-3-yl)carbonyl-L-prolyl]-N- methyl-N-phenylmethyl-3-(2-naphthyl)-L
      alaninamide (FK888), inhibited 5-HT (3 x 10(-6) M: submaximal concentration)
      induced antral contractions concentration dependently and shifted the 5-HT
      concentration-response curve to the right. 5-HT (3 x 10(-6) M)-induced corporal
      relaxation was not affected by tetrodotoxin, ketanserin, granisetron or
      GR113808A. At 10(-7) M, neither methysergide nor NAN-190 affected corporal
      relaxation, but at a high concentration (10(-6) M) they both inhibited it and
      shifted the 5-HT concentration-response curve to the right. We conclude that 5-HT
      induced antral contraction is mediated by cholinergic neurons via 5-HT2A, 5-HT3
      and 5-HT4 receptors, whereas corporal relaxation is mediated via 5-HT1-like
      receptors on smooth muscle that are sensitive to methysergide and NAN-190.

PMID- 8858307
TI  - SR 140333 prevents potentiation by citric acid of plasma exudation induced by
      histamine in airways.
AB  - We here report a model of potentiation by citric acid of airway microvascular
      leakage induced by histamine and its modification by the tachykinin NK1 and NK2
      receptor antagonists, SR 140333 ((S)1-{2-[3-(3,4-dichlorophenyl)-1-(3-iso
      propoxyphenylacetyl)p iperidin- 3-yl]ethyl}-phenyl-1-azoniabicyclo[2.2.2]octane,
      chloride) and SR 48968 (S)-N-methyl-N-[4-(4-acetyl-amino-4-phenylpiperidino)-2
      (3,4- dichlorophenyl-butyl]benzamide. Guinea-pigs exposed to an acrosol of citric
      acid 0.4 M for 1 h developed 24 h later a hyperresponsiveness to histamine
      induced microvascular leakage measured by Evans blue dye extravasation. SR
      140333, but not SR 48968 (1 mg kg-1 given each once 30 min before citric acid
      exposure), prevented this potentiation. These results provide further evidence of
      the role of tachykinin and tachykinin NK1 receptor stimulation on airway
      hyperresponsiveness and its neurogenic inflammatory component.

PMID- 8858308
TI  - NMDA receptor antagonists block development of tolerance to m-CPP-induced
      increases in ACTH concentrations in rats.
AB  - We have recently demonstrated that a single administration of m
      chlorophenylpiperazine (m-CPP, a preferential 5-HT2C receptor agonist) produces
      tolerance to its stimulatory effect on adrenocorticotropic hormone (ACTH)
      concentrations when challenged 24 h later with the same dose of m-CPP. In the
      present study, we studied the effects of pretreatment with various N-methyl-D
      aspartate (NMDA) receptor antagonists on development of tolerance to m-CPP's
      stimulatory effect on ACTH concentrations. Pretreatment with various NMDA
      receptor antagonists such as 5.7-dichlorokynurenic acid (1.0 mg/kg), 3-amino-1
      hydroxy 2-pyrrolidone (1.0 mg/kg), dizocilpine (0.1 mg/kg) and ifenprodil (1.0
      mg/kg) injected 30 min before the first injection of m-CPP (2.5 mg/kg) blocked
      development of tolerance to m-CPP's stimulatory effect on ACTH concentrations in
      rats injected 24 h later with the same dose (2.5 mg/kg) of m-CPP. These findings
      suggest that tolerance to postsynaptic 5-HT2C receptor-mediated response is
      initiated though stimulation of NMDA receptor complex and, furthermore,
      demonstrate a functional interaction between the 5-HT and glutamate systems.

PMID- 8858309
TI  - Effect of the bradykinin B2 receptor antagonist Hoe140 in experimental
      pneumococcal meningitis in the rat.
AB  - To elucidate the role of bradykinin in the complex pathophysiology of bacterial
      meningitis we investigated the effect of the bradykinin B2 receptor antagonist
      Hoe140, icatibant (D-Arg[Hyp3-Thi5-D-Tic7-Oic8]-bradykinin), on
      pathophysiological alterations in experimental pneumococcal meningitis. Untreated
      rats injected intracisternally (i.c.) with heat-killed pneumococci developed an
      increase of regional cerebral blood flow (185.4 +/- 27.4%, baseline 100%, mean +/
      S.D.), brain water content (79.16 +/- 0.23%), intracranial pressure (21.4 +/-
      6.0 mm Hg), and white blood cell count in the cerebrospinal fluid (CSF) (4621 +/-
      1894 cells/microliter) within 6 h after i.c. challenge. Treatment with Hoe140
      (0.1 mg/kg i.v. at baseline and 0.05 mg/kg s.c. at 2 h after i.c. challenge)
      attenuated the increase of brain water content (78.53 +/- 0.28%; P < 0.05),
      intracranial pressure (7.5 +/- 2.2 mm Hg; P < 0.05), and regional cerebral blood
      flow (128.6 +/- 23.1%; P < 0.05), and reduced CSF pleocytosis (2690 +/- 1898
      cells/microliter. N.S.). When treatment was started 4 h after i.c. challenge
      Hoe140 reduced intracranial pressure (P < 0.05), but was no more capable to
      significantly influence the other pathophysiological parameters. Treatment with
      lower (0.01 mg/kg i.v. at baseline, followed by 0.005 mg/kg s.c. at 2 h) and
      higher (2 mg/kg i.v., followed by 1 mg/kg s.c. at 2 h) concentrations of Hoe140
      was ineffective. Likewise, i.c. injection of Hoe140, at different dosages (4
      nmol, 40 nmol, 400 nmol) did not significantly alter the pathophysiological
      parameters in pneumococci-induced meningitis, but caused changes in mean arterial
      blood pressure at dosages greater than 4 nmol. We conclude that bradykinin is
      involved as an inflammatory mediator of microvascular changes, brain edema, and
      increased intracranial pressure during the early phase of experimental
      pneumococcal meningitis.

PMID- 8858310
TI  - Dual effect of glyburide, an antagonist of KATP channels, on metabolic inhibition
      induced Ca2+ loading in cardiomyocytes.
AB  - Whether sulfonylurea therapy, which blocks ATP-sensitive K+ (KATP) channels,
      impedes endogenous cardioprotective mechanisms during cellular metabolic
      impairment remains controversial. Therefore, the effect of glyburide, a prototype
      sulphonylurea drug, on cytosolic Ca2+ concentration and KATP channel activity,
      was measured in 2-4-dinitrophenol-treated guinea-pig cardiomyocytes, using
      epifluorescent digital-imaging and cell-attached patch-clamp electrophysiology.
      Dinitrophenol (200 microM), which uncouples oxidative phosphorylation, induced
      opening of KATP channels and Ca2+ loading. Glyburide (6 microM) which reduced the
      opening of KATP channels, aggravated Ca2+ loading only when applied to
      dinitrophenol-pretreated myocytes but not when applied with dinitrophenol
      treatment. We conclude that a blocker of KATP channels has differential effects
      upon dinitrophenol-induced intracellular Ca2+ loading, which appear to depend
      upon the stage of metabolic insult.

PMID- 8858311
TI  - Dual effects of endothelin-1 on the L-type Ca2+ current in ventricular
      cardiomyocytes.
AB  - The effects of endothelin-1 on the L-type Ca2+ current were studied in rabbit
      ventricular cardiomyocytes, using both the 'perforated' and the conventional
      'ruptured' whole-cell patch-clamp techniques. Endothelin-1 exerts a dual effect
      on ventricular cardiomyocytes using experimental conditions which minimize
      intracellular dialysis; endothelin-1 produced both an increase (10(-9) M) and a
      decrease (10(-8) M) in the L-type Ca2+ current using the perforated patch-clamp
      technique. However, using the ruptured patch-clamp technique, endothelin-1
      produced a similar decrease in L-type Ca2+ current at 10(-8) M, but no effect was
      observed at a concentration of 10(-9) M. These effects suggest multiplicity in
      the receptor-effector coupling mechanism.

PMID- 8858312
TI  - GABAB receptor antagonism by resolved (R)-saclofen in the guinea-pig ileum.
AB  - The GABAB receptor antagonist saclofen (3-amino-2-(4-chlorophenyl)propylsulphonic
      acid) has been resolved by chiral high-performance liquid chromatography. The
      enantiomer (R)-saclofen, but not (S)-saclofen, reversibly antagonised the (R,S)
      baclofen-induced depression of cholinergic twitch contractions in the guinea-pig
      ileum with an apparent pA2 of 5.3. Also, 2-hydroxy-saclofen was resolved by the
      same method, its (S)-enantiomer yielding an apparent pA2 of 5.0. This method
      provides a convenient resolution of these antagonists.

PMID- 8858313
TI  - Neoplasia distal to the splenic flexure in patients with proximal colon cancer.
AB  - BACKGROUND: Current American Cancer Society recommendations are that persons aged
      50 years or older undergo screening flexible sigmoidoscopy every 3 to 5 years. In
      clinical practice, persons with adenomas at sigmoidoscopy are generally referred
      for full colonoscopy. However, cancers proximal to the splenic flexure may not be
      accompanied by neoplasia distal to the splenic flexure. METHODS: In order to
      estimate how often screening flexible sigmoidoscopy would be negative in persons
      with proximal cancer, we retrospectively reviewed 2053 consecutive colorectal
      cancer cases diagnosed from 1988 to 1994. Seven hundred ninety-nine (38.9%) had
      tumors proximal to the splenic flexure. We selected 358 study cases based on full
      colonoscopy performed and the colonoscopy reports available. RESULTS: Colonoscopy
      demonstrated distal adenomas in 77 cases (21.5%): 29 (8.1%) had hyperplastic
      polyps only, 4 (1.1%) had synchronous cancer, and 248 (69.3%) had no distal
      polyps. In this population, 77.4% of patients with proximal colon cancer had no
      distal neoplasia. We estimate that 30% of all patients with colorectal cancer
      would have a negative screening flexible sigmoidoscopy. CONCLUSIONS: Prospective
      evaluation of colonoscopic findings in persons with proximal cancers is needed.
      Ongoing evaluation of colonoscopy as a general screening test is appropriate.

PMID- 8858314
TI  - Prevalence of proximal colonic polyps in average-risk asymptomatic patients with
      negative fecal occult blood tests and flexible sigmoidoscopy.
AB  - BACKGROUND: Proximal colonic adenomas were found in 13% to 37% of patients
      without distal adenomas who underwent colonoscopy. Fiberoptic flexible
      sigmoidoscopy (FFS) was not performed prior to colonoscopy in all studies except
      one. The proximal colon at colonoscopy was defined as that portion of the colon
      proximal to either the descending-sigmoid junction or 60 cm from the anus while
      withdrawing the colonoscope. These estimates may not reflect exact colonic
      location when a 60 cm length sigmoidoscope is fully inserted. Therefore, the aim
      of our study was to determine the prevalence of proximal colonic neoplasms in
      asymptomatic patients with average risk for colon cancer, aged 50 years and over,
      with negative fecal occult blood tests and without adenomas at FFS. METHODS:
      Colonoscopy was performed in 80 patients without and 95 patients with adenomas at
      FFS. Polypectomy was done using hot biopsy forceps or snare cautery. RESULTS:
      Twenty-four proximal colonic adenomas (19 < 1 cm and 5 > or = 1 cm) were found in
      18 of 80 patients (23%) with normal FFS compared with 39 proximal colonic
      adenomas (32 < 1 cm and 7 > or = 1 cm), in 28 of 95 patients (29%) with adenomas
      at FFS (p = 0.31). In patients with normal FFS, there were 20 tubular, 2
      tubulovillous, and 2 villous (1 with severe dysplasia) adenomas. In patients with
      adenomas at FFS, there were 31 tubular, 5 tubulovillous, and 3 villous (1 with
      severe dysplasia) adenomas. CONCLUSIONS: Proximal colonic adenomas are found in
      up to one fourth of asymptomatic average-risk patients with negative fecal occult
      blood test and both with and without adenomas at FFS. The adenomas in both groups
      have similar size, histology, and location. Severe dysplasia is rarely present.

PMID- 8858315
TI  - Should ERCP be routine after an episode of "idiopathic" pancreatitis? A cost
      utility analysis.
AB  - BACKGROUND: Patients often recover from an episode of acute pancreatitis with
      conservative therapy and without an identified cause. The options include
      proceeding with ERCP to identify and treat an occult common bile duct stone or
      performing the procedure only after a second episode of idiopathic pancreatitis
      occurs. METHODS: Decision analysis (SMLTREE software) was used to determine
      incremental cost-utility. Variables were estimated from a search of the
      literature, a utility analysis involving health professionals familiar with the
      question, and a retrospective review of hospital charts and costs. RESULTS: This
      model estimates an incremental utility gain for the prompt ERCP approach of 1.0
      quality-adjusted life weeks per patient at an incremental cost of $245
      (Canadian). This yields a cost-utility ratio of $12,740 (Canadian) per quality
      adjusted life year. The result was highly sensitive to the probability of finding
      an occult common bile duct stone. CONCLUSION: Routine ERCP is of marginal overall
      benefit, but is of more substantial benefit and is more cost-effective in a
      subgroup of patients with a greater probability of having an occult common duct
      stone.

PMID- 8858316
TI  - Hypoxemia during diagnostic laparoscopy: a prospective study.
AB  - BACKGROUND: Laparoscopic liver biopsy can be safely performed using local
      anesthesia and intravenous sedation, but the frequency of hypoxemia is unknown.
      METHODS: We prospectively studied 68 patients undergoing diagnostic laparoscopy
      and liver biopsy managed by a standard protocol. RESULTS: The mean duration of
      laparoscopy was 27 +/- 5.53 minutes; the mean dose of diamorphine administered
      was 6.9 +/- 2.7 mg; diazepam, 7.05 +/- 3.52 mg. The baseline arterial oxygen
      saturation was 95.6% +/- 2.5% and trough was 85% +/- 5.1%. A fall of greater than
      4% saturation from the baseline occurred in 64 out of 68 patients (94%). The mean
      decrease in saturation was 10.1% +/- 5.4%. An arterial oxygen saturation of less
      than 85% was seen in 32 patients (47%). There was no correlation between the fall
      in oxygen saturation and the dose of diamorphine or diazepam, the duration of
      procedure, body mass index, hemoglobin, or volume of pneumoperitoneum induced.
      One-way analysis of the variance failed to show a significant relationship
      between the degree of oxygen saturation and Child's class, etiology of liver
      disease, or smoking habit. CONCLUSIONS: In this study, we demonstrated that
      significant desaturation is common in diagnostic laparoscopy with liver biopsy
      and is likely due to a combination of different pharmacologic and physiologic
      effects. We recommend continuous monitoring of both arterial oxygen saturation
      and supplemental oxygen for all patients throughout laparoscopy.

PMID- 8858317
TI  - Evaluation of per-procedure equipment costs in an outpatient endoscopy center.
AB  - BACKGROUND: As disposable endoscopes become available, we need baseline costs
      associated with reusable instruments to make financially intelligent choices.
      Accordingly, we analyzed the per-use cost of several types of gastrointestinal
      endoscopes at our institution. METHODS: Records of 44 gastrointestinal endoscopes
      were analyzed. Data defined included purchase price, repair and cleaning expense
      (labor and materials), and number of uses. The labor cost per-use associated with
      endoscope cleaning was estimated by taking an average time required to clean an
      endoscope multiplied by the technician's salary. RESULTS: The average number of
      years of endoscope use varied from 4.6 to 6.9 years contingent on the type of
      endoscope. For flexible sigmoidoscopes, the average total cost per use was $8.35,
      and for colonoscopes the cost was $21.81. For gastroscopes and diagnostic and
      therapeutic duodenoscopes, costs were $20.99, $49.15, and $45.16, respectively.
      CONCLUSIONS: (1) Excluding costs associated with the procedure itself (admit
      recovery, drugs, disposable equipment, and procedural personnel), total peruse
      scope cost ranged from a low of $8.35 for the flexible sigmoidoscope to $49.15
      for the diagnostic duodenoscope. (2) The most important variables associated with
      per-use endoscope cost included number of uses, initial purchase price, and
      repair costs. (3) Techniques such as the above can be used to define per
      procedure costs for a particular practitioner or institution.

PMID- 8858318
TI  - Antireflux operations at flexible endoscopy using endoluminal stitching
      techniques: an experimental study.
AB  - BACKGROUND: Three antireflux operations-gastroplasty, fundoplication, and
      anterior gastropexy-were developed for performance at flexible endoscopy without
      laparotomy or laparoscopy. METHODS: An endoscopic sewing machine mounted on a
      standard gastroscope, endoscopic knotting devices, overtube, and nylon thread
      were used to perform these operations in adult beagle dogs. RESULTS: Gastroplasty
      (n = 10) was accomplished by suturing the anterior and posterior wall of the
      stomach to create a gastric tube (neoesophagus) along the lesser curve. An
      anatomic arrangement similar to fundoplication (n = 6) was achieved by
      invaginating the esophagus and fixing it to the stomach 2 cm distal to the
      cardioesophageal junction. Anterior gastropexy (n = 6) was performed using a
      technique similar to that used in creating percutaneous gastrostomies. There was
      no mortality. Ninety percent of sutures were seen at repeat endoscopy at 4 to 8
      week intervals. The gastroplasty group was selected for more extensive
      evaluation. Manometry using a three-channel perfused catheter system before and
      after the procedures showed an increase in the lower esophageal sphincter
      pressure (preoperative median 4.6 mm Hg; post-operative median 13.33 mm Hg, p =
      0.008) and cardiac yield pressures (preoperative median 10 mm Hg; postoperative
      median 19 mm Hg, p = 0.007). CONCLUSIONS: This study demonstrates the feasibility
      of performing antireflux operations at flexible endoscopy, without laparoscopy or
      laparotomy, by use of endoluminal suturing techniques.

PMID- 8858319
TI  - Endoscopic decompression for acute colonic pseudo-obstruction.
AB  - BACKGROUND: Acute colonic pseudo-obstruction is often treated by colonoscopic
      decompression. Efficacy, safety, and outcome of endoscopic decompression was
      assessed. METHODS: Colonoscopic decompressions from 1988 to 1994 were reviewed.
      Resolution without further endoscopic intervention was defined as clinical
      success. RESULTS: Acute colonic pseudo-obstruction was diagnosed in 50 patients.
      Thirty-three cases followed surgery or trauma and 17 developed during severe
      medical illness. Orthopedic joint surgery was most common. Nineteen of 50
      patients (38%) had severe underlying medical disease. Forty-one patients (82%)
      had one colonoscopic decompression with clinical success in 39 (95%). Nine
      patients (18%) required multiple (2 to 4) colonoscopic decompressions with
      clinical success in 5 (56%). A decompression tube positioned in the right colon
      (57%) and in the transverse colon (33%) had similar clinical success. In 8
      procedures a decompression tube was not placed, with poor clinical success (25%).
      The overall clinical success of colonoscopic decompression was 88% (44 of 50). An
      endoscopic perforation occurred in 1 patient (2%). Overall hospital mortality was
      30%. CONCLUSIONS: Colonoscopic decompression is effective and safe for acute
      colonic pseudo-obstruction that does not respond to conservative therapy. Most
      patients will respond to one colonoscopic decompression with decompression tube
      placement. Complete colonoscopy and cecal tube placement is unnecessary.

PMID- 8858320
TI  - Use of high-resolution endoscopic ultrasonography to assess esophageal wall
      damage after pneumatic dilation and botulinum toxin injection to treat achalasia.
AB  - OBJECTIVE: The purpose of this study was to utilize high-resolution endoscopic
      ultrasonography to assess esophageal wall damage in patients with achalasia
      treated by either pneumatic dilation or botulinum toxin injection and to compare
      their symptomatic response. METHODS: Twenty-nine patients were treated with
      pneumatic dilation (11) or botulinum toxin injection (18) in a nonrandomized,
      controlled manner. An achalasia balloon dilator inflated at the gastroesophageal
      junction was used for dilation. Botulinum toxin was injected during endoscopy
      into the gastroesophageal junction. Endoscopic ultrasonography was performed at
      the level of the diaphragm before, immediately after, and 24 hours after
      treatment. Symptoms were assessed before and 7, 30, 60, and 90 days after
      therapy. RESULTS: The mucosal-submucosal thickness increased significantly
      immediately after pneumatic dilation, but normalized by 24 hours. No significant
      change in mucosal-submucosal thickness occurred after botulinum toxin injection.
      No significant alteration in muscularis propria thickness was observed after
      either procedure. Dysphagia and regurgitation improved significantly at 7, 30,
      60, and 90 days after both procedures. CONCLUSIONS: Pneumatic dilation produced
      transient thickening of the mucosa-submucosa, but no thickening or breaks in the
      muscularis propria. This transient wall damage suggestive of edema was not seen
      after botulinum toxin injection. Over a 3-month period, botulinum toxin was
      equivalent to pneumatic dilation in relieving dysphagia and regurgitation in
      patients with achalasia.

PMID- 8858321
TI  - Diagnosis of common bile duct stones by intravenous cholangiography: prediction
      by ultrasound and liver function tests compared with endoscopic retrograde
      cholangiography.
AB  - BACKGROUND: Routine intravenous cholangiography using the safer contrast medium,
      meglumine iotroxate, may be a useful investigation prior to laparoscopic
      cholecystectomy for the detection of suspected common bile duct stones. We
      compared this with endoscopic cholangiography. METHODS: Eighty-one consecutive
      nonjaundiced patients (mean age 62 years; range 20 to 90) with suspected common
      bile duct stones referred for endoscopic cholangiography to one center underwent
      intravenous cholangiography that was considered positive if it detected ductal
      stones. The ability of ultrasound scans and liver function tests to predict
      ductal stones was also assessed. RESULTS: Sixty patients had both endoscopic and
      intravenous cholangiograms performed. Thirteen out of 27 patients with ductal
      stones confirmed by endoscopic cholangiography had positive intravenous
      cholangiograms, and 29 out of 30 with no stones had negative intravenous
      cholangiograms. The sensitivity for intravenous cholangiography was 48%,
      specificity 97%, positive predictive value 93%, negative predictive value 67%,
      and accuracy 73%. For ultrasound scans the positive predictive value was 69%;
      negative predictive value was 78%. For liver function tests the positive
      predictive value was 68%; negative predictive value was 93%. CONCLUSIONS:
      Intravenous cholangiography cannot be recommended instead of endoscopic
      cholangiography except in situations where the latter is not readily available.
      Ultrasound and liver function tests are useful in predicting ductal stones.

PMID- 8858322
TI  - Percutaneous endoscopic gastrostomy: a randomized prospective comparison of early
      and delayed feeding.
AB  - BACKGROUND: It has been customary to initiate feeding through percutaneous
      endoscopic gastrostomy (PEG) tubes 24 hours or more after placement of these
      tubes. Recent changes in practice environment and emphasis on early discharge of
      hospitalized patients prompted us to evaluate early PEG feeding in a randomized
      prospective manner. METHODS: Forty-one patients were included in the study. After
      an informed consent, the patients were randomly assigned to two groups. Groups I
      (21 patients) received tube feedings 3 hours and Group II (20 patients) received
      feedings 24 hours after PEG placement. All patients received an Iso-osmolar
      formula by continuous infusion at 30 ml/hour for the first 24 hours of feeding.
      The rates were then increased to 70 ml/hour. Residual volumes, tube length,
      peristomal leakage, and vital signs were checked, and a global assessment was
      done every 4 hours. Evaluation by a physician was done every 24 hours for 72
      hours. If the residual volume was more than 60 ml (significant residual volume),
      the tube feedings were held for 2 hours. Patients exited the study at 72 hours
      from the time of procedure. All deaths were recorded to calculate 30-day
      mortality. RESULTS: One patient (Group 2) died during the study period. Three
      patients (two in Group 1 and one in Group 2) had a significant residual volume.
      One patient (Group 1) had local skin infection requiring treatment. None of the
      patients had any signs of peritonitis or systemic infection. CONCLUSION: Early
      PEG tube feeding (3 hours after tube placement) is as safe as next day feeding in
      elderly patients.

PMID- 8858324
TI  - Colonoscopy without premedication versus barium enema: a comparison of patient
      discomfort.
AB  - BACKGROUND: Colonoscopy is considered a painful procedure requiring routine
      intravenous sedation. We investigated whether unsedated colonoscopy causes more
      discomfort than barium enema. METHODS: Procedure-related discomfort was
      determined in 100 consecutive patients undergoing colonoscopy without
      premedication and in an equal number of patients referred for sigmoidoscopy and
      barium enema. All patients underwent such examinations for the first time and had
      no history of previous bowel surgery. During colonoscopy, sedation was offered if
      significant pain or discomfort occurred. RESULTS: In patients without stenosis
      and with satisfactory preparation, the completion rate of colonoscopy was 95%.
      Five percent of all patients undergoing endoscopy required sedation. On an analog
      scale ranging from 1 to 9, patients undergoing colonoscopy and barium enema
      reported similar ratings for procedure related discomfort (3.2 +/- 1.7 and 3.1 +/
      1.9) and for discomfort caused by bowel preparation (3.2 +/- 2.1 and 3.1 +/-
      1.8). Eighty-seven percent of all patients undergoing colonoscopy stated that
      they would prefer no premedication in the event of repeated examinations.
      CONCLUSIONS: Colonoscopy with sedation on demand does not cause more discomfort
      than barium enema and will be accepted by the vast majority of patients
      undergoing this procedure.

PMID- 8858323
TI  - Detection of dysplasia at colonoscopy using laser-induced fluorescence: a blinded
      study.
AB  - BACKGROUND: Laser-induced fluorescence spectroscopy has the potential to detect
      colonic dysplasia in vivo. However, previous studies have limited their analyses
      to multivariate regression techniques and unblinded retrospective evaluation. The
      purpose of this study was to develop a probability-based algorithm to detect
      colonic dysplasia using laser-induced fluorescence spectroscopy and to evaluate
      it in a blinded manner. METHODS: Fluorescence spectra were collected from normal
      mucosa and colonic polyps during colonoscopy using 370 nm excitation. Tissue was
      classified as normal, hyperplastic, or adenomatous by histologic examination.
      Preliminary data was used to devise an algorithm to differentiate tissue type
      based on probability distributions of the fluorescence intensity at 460 nm and
      the ratio of the intensity at 680 nm to that at 600 nm. The algorithm was then
      tested in a blinded fashion. RESULTS: The algorithm correctly determined the
      tissue type in 88% of cases, equal to the agreement of independent pathologists.
      Sensitivity, specificity, and positive predictive value for the detection of
      dysplasia was 90%, 95%, and 90%, respectively. CONCLUSIONS: Dysplasia was
      detected in vivo using fluorescence spectroscopy and a probability-based
      algorithm. This method may form the basis for a new surveillance technique for
      patients with increased risk for dysplastic transformation.

PMID- 8858325
TI  - Standardization of clinical criteria required for use of the 12.5 millimeter
      barium tablet in evaluating esophageal lumenal patency.
AB  - BACKGROUND: Although the barium tablet is commonly used in evaluating lumenal
      patency of the esophagus, the conditions under which the tablet should traverse a
      normal esophagus have not been established. This study was designed to
      standardize the minimal criteria required to ensure successful esophageal transit
      of a commercially available barium tablet in normal subjects. METHODS: Each of 20
      volunteers swallowed a standard 12.5 mm barium tablet under fluoroscopy in the
      supine, 45 degrees incline, and upright positions. Tablets were swallowed dry and
      with fixed volumes of water (15, 30, 60, and 100 cc). Success of pill passage
      into the stomach was determined by fluoroscopy at 20, 40, 60, and 90 seconds.
      RESULTS: Successful pill passage correlated significantly with position (passing
      17.0%, 66.5%, and 69.7% in the supine, incline, and upright position,
      respectively; p < .0001) and volume of water ingested (passing 9.1% when
      swallowing dry, and 38.7%, 55.8%, 70.0%, and 81.6% with 15, 30, 60, and 100 cc of
      water, respectively; p < or = .004). Duration of time beyond 20 seconds failed to
      affect rate of pill passage. Ingestion of 60 cc of water in the incline position
      was associated with a 95% pill passage, a rate significantly greater than any
      position at lower volumes. Increasing water volume above 60 cc or assuming the
      upright position did not increase this passage rate further. CONCLUSIONS: The
      minimum criteria required to optimize successful transit of a 12.5 mm barium
      tablet through a normal esophagus is to perform the test in the 45 degrees
      incline position with 60 cc of water for a period of 20 seconds. Failure of the
      pill to pass under these conditions may suggest a true structural abnormality of
      the esophagus.

PMID- 8858327
TI  - Directed guide wire placement during ERCP using a papillotome.

PMID- 8858328
TI  - Simultaneous cannulation and needle-knife papillotomy using a large-channel
      duodenoscope.

PMID- 8858326
TI  - Snare beside-a-wire biliary stent exchange: a method that maintains access across
      biliary strictures.

PMID- 8858329
TI  - Initial experience with a new babyscope for endoscopic retrograde
      cholangiopancreaticoscopy.

PMID- 8858330
TI  - Obstructive jaundice caused by ampullary metastases of an endometrioid
      adenocarcinoma.

PMID- 8858331
TI  - Endosonography of an abdominal bronchogenic cyst.

PMID- 8858332
TI  - Diaphragm-like strictures of the right colon induced by indomethacin
      suppositories: evidence of a systemic effect.

PMID- 8858333
TI  - Colon cancer screening: what is the question?

PMID- 8858334
TI  - Ensuring quality care for patients with digestive diseases.

PMID- 8858335
TI  - Biopsies of the ampullary region in sphincter of Oddi dysfunction.

PMID- 8858336
TI  - Laparoscopically assisted panenteroscopy for snare excision.

PMID- 8858337
TI  - Whistle-tip suction catheter for pre-endoscopic aspiration in achalasia.

PMID- 8858338
TI  - Angioedema from oral polyethylene glycol electrolyte lavage solution.

PMID- 8858339
TI  - Perforation of the endoscope covering by needle-like ends of esophageal metal
      mesh stents.

PMID- 8858340
TI  - Perspectives: sequence data base searching in the era of large-scale genomic
      sequencing.
AB  - Large-scale sequencing of human and model organism genomes will have a profound
      impact on our ability to use sequence data base searching to predict the
      biochemical functions of sequences of interest. Despite the great value of more
      sequences in the data bases, a huge increase in data base size will also have
      adverse effects on data base searches. Upcoming problems will include (1) greatly
      increased search times, (2) an increase in background noise of high-scoring but
      biologically irrelevant matches, (3) inaccurate coding region prediction, leading
      to problems in protein data base searching, and (4) limited first-pass sequence
      annotation, making it difficult to determine the biological relevance of data
      base hits. Improved data base annotation tools and construction of smaller data
      bases of representative and highly-annotated sequences for first-pass analyses
      will be essential to deal with the impending flood of new genomic sequence.

PMID- 8858341
TI  - The Japanese Rice Genome Research Program.

PMID- 8858342
TI  - A linkage map of the ovine X chromosome.
AB  - A genetic linkage map of the ovine X chromosome containing type I and type II
      markers has been constructed. The map contains 7 known gene markers and 14
      microsatellite markers with a recombination length of 141.9 cM. Segregation of
      polymorphic markers was observed in a three-generation pedigree containing 480
      animals. The maximum number of informative meioses was 912. Additional
      information was obtained for some markers by following segregation in the
      AgResearch International Mapping Flock, consisting of nine three-generation full
      sib pedigrees. A pseudoautosomal region containing two markers has been
      identified at one end of the linkage map. Comparisons with mouse and human X
      chromosomes confirms the observation of Ohno (1973) that the gene content of the
      mammalian X chromosome is retained. In particular, the conserved grouping of the
      genes PHKA1, ATP7A, and XIST observed in both the human and the mouse X
      chromosome appears to be conserved in the sheep X chromosome, and XIST has been
      mapped to near the center of the chromosome. This study provides the first
      reported genetic linkage map combining both type I and type II markers for any
      ruminant X chromosome.

PMID- 8858343
TI  - Direct cDNA selection with DNA microdissected from mouse chromosome 16: isolation
      of novel clones and construction of a partial transcription map of the C3-C4
      region.
AB  - A group of cDNA segments was selected by direct hybridization of mouse cerebellar
      cDNAs against genomic DNA pools generated by microdissection of the mouse
      chromosome 16 (MMU16) C3-C4 region. After elimination of repetitive sequences and
      adjustment for redundancy among clones, 34 novel cDNA fragments were isolated.
      The MMU16 origin of clones was confirmed by genetic linkage mapping. Reverse
      transcription PCR indicated that approximately 68% of the cDNAs represent
      transcripts that are expressed in adult mouse cerebellum. Northern blotting
      showed that some of these are predominantly or solely expressed in brain. This
      work demonstrates that DNA microdissected from banded MMU16 can be used for
      direct cDNA selection, thus enabling construction of a new, region-specific
      partial transcription map. This selected cDNA library should be a useful reagent
      for further molecular neurobiological studies.

PMID- 8858344
TI  - Characterization of the mouse histone gene cluster on chromosome 13: 45 histone
      genes in three patches spread over 1Mb.
AB  - The histone gene cluster on mouse chromosome 13 has been isolated and
      characterized. Using overlapping YAC clones containing histone genes from
      chromosome 13, a contig of approximately 2 Mb has been defined. It contains 45
      histone genes, organized in three patches containing tightly clustered genes. An
      80-kb patch (patch III) containing 12 histone genes is near one end of the
      contig, and a similar-sized patch (patch I) containing 15 histone genes is near
      the other end of the contig, located at least 500 kb from the central patch
      (patch II) of histone genes. The entire cluster contains six histone H1 genes,
      including the testis-specific histone H1t gene that maps to the middle of the
      cluster. All nine histone H3 genes in this cluster have been sequenced, and their
      level of expression determined. Each histone H3 gene is distinct, with five genes
      encoding the H3.2 protein subtype and four genes encoding the H3.1 protein. They
      are all expressed, with each histone H3 gene accounting for a small proportion of
      the total histone H3 mRNA.

PMID- 8858345
TI  - Characterization of the 55-kb mouse histone gene cluster on chromosome 3.
AB  - The histone gene cluster on mouse chromosome 3 has been isolated as a series of
      overlapping P1 clones, covering 110-120 kb, by probing with the histone H3-614
      gene that had been mapped previously to mouse chromosome 3. There are genes for
      10 core histone proteins present in a 55-kb cluster within this contig. There are
      three histone H3 genes, two of which are identical; four histone H2a genes, two
      of which are identical, one histone H4 gene; and two histone H2b genes. These
      histone H3 and H2a genes encode approximately 40% of the total H3 and H2a mRNA,
      whereas the histone H4 and histone H2b genes encode < 10% of the total H4 and H2b
      mRNA. There are no histone H1 genes present in this cluster. All of the histone
      H2a genes encode histone H2a.2 proteins (or variants of H2a.2), and account for
      all the H2a.2 genes in the mouse genome. All three histone H3 genes encode the
      histone H3.2 protein. A 21-kb region containing the adjacent H3-614 and H2a-614
      genes has been duplicated and is present in an inverted repeat separated by 4.5
      kb. The other two H2a genes are adjacent, with the 3' ends of their mRNAs
      separated by only 49 nucleotides in the DNA and the U7 snRNP binding sites
      separated by only 20 nucleotides. One of the histone H2b genes has lost the stem
      loop sequence characteristic of the replication-dependent histone mRNAs and
      encodes only polyadenylated mRNAs.

PMID- 8858347
TI  - Evidence for linkage of regions on chromosomes 6 and 11 to plasma glucose
      concentrations in Mexican Americans.
AB  - The genetic factors involved in type II diabetes are still unknown. To address
      this problem, we are creating a 10 to 15 cM genetic map on 444 individuals from
      32 Mexican American families ascertained on a type II diabetic proband. Using
      highly polymorphic microsatellite markers and a multipoint variance components
      method, we found evidence for linkage of plasma glucose concentration 2 hr after
      oral glucose administration to two regions on chromosome 11: beta-hemoglobin
      (HBB) and markers D11S899/D11S1324 near the sulfonylurea receptor (SUR) gene. Iod
      scores at these two loci were 2.77 and 3.37, respectively. The SUR gene region
      accounted for 44.7% of the phenotypic variance. Evidence for linkage to fasting
      glucose concentration was also observed for two loci on chromosome 6, one of
      which is identical to a proposed susceptibility locus for type I diabetes
      (D6S290). When diabetics were excluded from the analyses, all Iod scores became
      zero, suggesting that the observed linkages were with the trait diabetes rather
      than with normal variation in glucose levels. Results were similar whether all
      diabetics were included in the analyses or only those who were not under
      treatment with oral antidiabetic agents or insulin.

PMID- 8858346
TI  - Isolation and mapping of novel mouse brain cDNA clones containing trinucleotide
      repeats, and demonstration of novel alleles in recombinant inbred strains.
AB  - Abnormal expansion of trinucleotide repeats (TRs) has now been implicated in the
      pathogenesis of at least nine human genetic disorders, particularly those in
      which anticipation and/or fragile sites have been demonstrated. Anticipation, the
      phenomenon of increasing severity of phenotype in successive generations, has
      never been seen in species other than man. Nevertheless, animal models for the
      dynamic mutation of TRs would be extremely valuable. We have screened a mouse
      brain cDNA library in an attempt to identify clones representing each of the 10
      possible classes of trinucleotide repeat. Thirty-seven clones were analyzed in
      detail. Of the 37 sequences, 18 displayed significant levels of homology with
      sequences in GenBank, 10 of them with human expressed sequence tags (ESTs). We
      then analyzed 25 of the clones by PCR of the sequence containing the repeat in a
      number of different mouse strains and species to assess levels of variability of
      repeat length. Of the 25 clones analyzed in this way, 64% showed length variation
      between Mus musculus spp. and Mus spretus, and 32% showed variation between Mus
      musculus musculus-derived standard laboratory inbred strains. Where variation was
      detected (17 repeat-containing clones in all), the gene was mapped by linkage
      analysis. None of the repeats isolated showed any signs of extreme expansion.
      However, two of the repeats were shown to have undergone size changes during the
      establishment of a number of recombinant inbred strains, suggesting that these
      repeats are at least moderately unstable.

PMID- 8858348
TI  - 14-3-3 epsilon has no homology to LIS1 and lies telomeric to it on chromosome
      17p13.3 outside the Miller-Dieker syndrome chromosome region.
AB  - Previously, we isolated several cDNA clones of the LIS1 gene implicated in Miller
      Dieker syndrome. Analysis of the 5' end of one of the clones (8-1), which was
      originally thought to represent the 5' end of LIS1, indicates a striking
      similarity to mouse 14-3-3 epsilon. We have isolated a full-length cDNA of human
      14-3-3 epsilon, for which sequence analysis reveals a strong nucleotide
      conservation with mouse 14-3-3 epsilon in both translated and untranslated
      regions (UTRs). Additionally, the predicted peptides of human, sheep, rat, and
      mouse 14-3-3 epsilon are identical. Using a 205-bp fragment common to LIS1 (8-1)
      and 14-3-3 epsilon as probe on adult and fetal multiple-tissue Northern blots, a 
      2-kb transcript is detected, identical to the pattern observed with a full-length
      14-3-3 epsilon cDNA probe. LIS1-specific transcripts of approximately 7.5 and
      approximately 5 kb are not detected by the 0.2-kb probe, indicating that the
      similarity between the 5' sequence of LIS1 (8-1) and the 3' UTR of 14-3-3 epsilon
      is not the result of shared homology between the two genes. Instead, clone 8-1 is
      a chimera of 14-3-3 epsilon and LIS1 partial cDNAs, and therefore its 5' sequence
      does not represent the LIS1 5' end. Interestingly, we have mapped the 14-3-3
      epsilon gene to the same chromosomal sub-band as LIS1 (17p13.3). However, 14-3-3
      epsilon lies telomeric to LIS1 and outside the Miller-Dieker syndrome chromosome
      region but in a region frequently deleted in several types of cancer, and is a
      reasonable candidate tumor suppressor gene.

PMID- 8858349
TI  - Identification of a novel paternally expressed transcript adjacent to snRPN in
      the Prader-Willi syndrome critical region.
AB  - Small nuclear ribonucleoprotein-associated polypeptide N (snRPN) and an anonymous
      transcript, PAR-5, are two of the paternally expressed transcripts mapped to the
      Prader-Willi syndrome critical region. Using long-range PCR, we have isolated the
      genomic interval between snRPN and PAR-5, identified a novel transcript in this
      region, and termed it PAR-SN. Northern analysis demonstrates that PAR-SN is
      expressed in brain, skeletal muscle, and heart. Like snRPN and PAR-5, PAR-SN is
      expressed exclusively from the paternal homolog in cultured lymphoblasts.
      Sequence analysis of the transcript revealed no significant open reading frame
      but did include a polymorphic dinucleotide repeat (CA)17.

PMID- 8858350
TI  - Cloning of 559 potential exons of genes of human chromosome 21 by exon trapping.
AB  - Chromosome 21 represents approximately 1% of the human genome, and its long arm
      has been estimated to contain 600-1000 genes. A dense linkage map and almost
      complete physical maps based on yeast artificial chromosomes (YACs) and cosmids
      have been developed. We have used exon trapping to identify portions of genes
      from randomly picked chromosome 21-specific cosmids, to contribute to the
      creation of the transcription (genic) map of this chromosome and the cloning of
      its genes. A total of 559 different sequences were identified after elimination
      of false-positive clones and repetitive elements. Among these, exons for 13 of
      the 30 known chromosome 21 genes have been "trapped." In addition, a considerable
      number of trapped sequences showed homologies to genes from other species and to
      human expressed sequence tags (ESTs). One hundred thirty-three trapped sequences
      were mapped, and every one mapped back to chromosome 21. We estimate that we have
      identified portions of up to approximately 40% of all genes on chromosome 21. The
      genic map of chromosome 21 provides a valuable tool for the elucidation of
      function of the genes and will enhance our understanding of the pathophysiology
      of Down syndrome and other disorders of chromosome 21 genes.

PMID- 8858351
TI  - Hybrid selection as a method of increasing mapping power for radiation hybrids.
AB  - Radiation hybrids have become a widely used tool for physical mapping. A drawback
      of the technique is that large numbers of hybrids are required to construct
      robust, high-resolution maps. The information contained within a panel of
      radiation hybrids is limited by the frequency of retention of chromosomal
      fragments from the donor cell line. In almost all experiments to date, the
      retention frequency has been below the optimal level; therefore, many hybrids are
      needed to produce high-quality maps. Because of the labor-intensive nature of
      large-scale mapping projects, it is important to make panels as small as
      possible. One method that has been adopted is to produce initially a large number
      of hybrids that are all typed with a few loci. Those hybrids showing
      satisfactorily high retention are admitted to the final panel and the rest are
      discarded. In this way, a panel of radiation hybrids with higher than expected
      retention can be created. Methods for conducting such a selection regime are
      discussed. To investigate the potential advantages of selecting hybrids based on
      their retention frequency, simulations were run under a variety of conditions. As
      expected panels with high retention (40%) provided better mapping resources than
      panels with lower (20%) retention. Beginning with an initial panel of 200
      hybrids, comparisons of a random sample of 100 hybrids and the set of those 100
      hybrids showing the highest marker retention demonstrated that selection may not
      be always the best strategy despite the increase in mean retention it yields. The
      selection of hybrids containing large numbers of fragments leads to an
      overestimation of the frequency of radiation-induced breaks. When breaks occur
      with high frequency (for example, when high radiation doses are used), the
      selection of hybrids leads to a loss of linkage and hence an inability to order
      the markers. As such, the merits of screening hybrids depends on both the
      radiation dose and the desired map resolution.

PMID- 8858352
TI  - Lasers, optical systems and safety in ophthalmology: a review.
AB  - This is a review of optical methods related to biomicroscopy and laser treatment
      of the posterior segment of the eye. Contact lenses can be used to observe
      optical structures and couple laser radiation into the eye for a vast range of
      conditions and techniques. A small laser spot size is indispensable for
      photodisruptive work, though this requires a large beam diameter at the pupil and
      therefore optical systems and techniques such as scleral indentation which
      maximize the pupillary beam diameter are preferred. For coagulation work the
      choice of beam focusing optics is crucial for optimum safety. Vitreous
      replacement can be used to change the refractive power of the eye and permit new
      combinations of treatment and optical systems. This review covers many aspects of
      laser irradiation of the eye. It should be clear that, with the multitude of
      different procedures and optical systems involved, the laser surgeon is faced
      with a daunting task in assessing and meeting safety limits.

PMID- 8858353
TI  - Vitreous laser absorption following fluorescein angiography in diabetic patients.
AB  - BACKGROUND: Sodium fluorescein staining of the vitreous following fluorescein
      angiography may interact with laser photocoagulation. METHODS: We evaluated the
      laser absorption by fluorescein in the vitreous when photocoagulation is
      performed following fluorescein angiography in 15 eyes of nine diabetic patients.
      Axial fluorescein concentration in the vitreous was measured by a scanning
      vitreal fluorophotometer. The amount of light absorbed by the fluorescein within
      the vitreous was calculated according to the Lambert-Beer law. RESULTS: The mean
      fluorescein concentration ranged from 2.93 ng cm-3 to 105.16 ng cm-3 at 1 h after
      injection of fluorescein and from 8.03 to 188.56 ng cm-3 after 4 h. Maximum laser
      absorption at 488 nm ranged from 6.79% (after 1 h) to 14.53% (after 4 h); at
      514.5 nm it ranged from 0.96% to 2.14%; at 532 nm it ranged from 0.03% to 0.07%.
      At lambda > 550 nm, laser absorption was found to be negligible. CONCLUSIONS: In
      order to optimize the effect of photocoagulation, especially during long
      photocoagulation sessions, argon blue laser (488 nm) should be avoided following
      fluorescein angiography. Argon green laser (514.5 nm) should be used within 1 h
      after fluorescein injection. Frequency-doubled Nd:YAG laser (532 nm), krypton
      laser (647 nm) or semiconductor diode laser (810 nm) may be used at any time.

PMID- 8858354
TI  - The prevalence of Toxoplasma antibody in patients with various ocular diseases in
      central Japan.
AB  - BACKGROUND: Ocular toxoplasmosis has been considered to be a largely asymptomatic
      infection because of the high seroprevalence of Toxoplasma antibodies and the low
      rate of clinical diagnosis. On the other hand, Toxoplasma infection has been
      reported to be associated with the other ocular disease. To investigate the
      association of Toxoplasma infection with the development of various ocular
      diseases, we studied Toxoplasma seroprevalence in patients with various ocular
      diseases. METHODS: We investigated Toxoplasma seroprevalence in 982 patients with
      various ocular diseases in central Japan. Then we compared the seroprevalence of
      anti-Toxoplasma antibodies. RESULTS: Of 982 patients with various ocular
      diseases, 122 (12.4%) had serological evidence of previous exposure to Toxoplasma
      gondii. There were no statistically significant differences among the patients
      with various ocular diseases. However, the seroprevalence in patients aged 40 to
      99 years with macular degenerative lesions was significantly higher than that in
      patients without these lesions (P < 0.05, Yates' correction). CONCLUSION: This
      result suggests that Toxoplasma infection could play some role in the development
      of a type of macular degenerative lesion.

PMID- 8858355
TI  - Does the presence of heparin and dexamethasone in the vitrectomy infusate reduce
      reproliferation in proliferative vitreoretinopathy?
AB  - BACKGROUND: Reproliferation following vitrectomy for proliferative
      vitreoretinopathy (PVR) causes redetachment in up to 55% of cases. Heparin and
      corticosteroids have each been shown to inhibit the development of proliferative
      vitreoretinopathy (PVR) in experimental models. However, little information is
      available on the use of these agents in humans. METHODS: In this pilot study, 62
      eyes of 62 patients with severe PVR requiring vitrectomy were prospectively
      randomized to receive either BSS Plus (control) or BSS Plus with heparin and
      dexamethasone (HD) in the infusate. RESULTS: After one operation, the retina was
      reattached in 42 (71%) of 59 eyes: 22 (65%) of 34 eyes in the control group and
      20 (80%) of 25 eyes in the HD group (P = 0.16). Reproliferation developed in
      26.5% of the control group (9 of 34 eyes) and 16% of the HD group (4 of 25 eyes;
      P = 0.26). Postoperative hemorrhage was significantly more frequent in the HD
      group (P = 0.02) but did not influence final visual or anatomic outcome. Hypotony
      was less frequent in the HD group but the difference was not significant (P =
      0.063). CONCLUSION: The trend from this randomized pilot study suggests that HD
      supplementation of the vitrectomy infusate may reduce the reproliferation rate in
      PVR and possibly reduce the rate of hypotony. Postoperative hemorrhage was more
      frequent with HD but did not cause redetachment or alter visual outcome. A
      multicenter trial involving more patients would be required to better evaluate
      the efficacy of HD as a pharmacologic adjunct to PVR surgery.

PMID- 8858356
TI  - Clinical and radiological presentation of 95 orbital lymphoid tumors.
AB  - BACKGROUND: Although most orbital lymphoid tumors are characterized by a slow,
      painless onset and a mass that molds to orbital structures, different
      presentations may occur. Intensity on T2-weighted MRI is a possible means for
      differentiating lymphoid tumors (hyperintense) from pseudotumors (hypointense).
      In addition, it is generally assumed that 75% of orbital lymphomas are at stage I
      on presentation. METHODS: The clinical, CT, and MRI presentation of 95 primary
      and secondary orbital lymphoid tumors (63 non-Hodgkin lymphomas and 32 lymphoid
      hyperplasias) and their histological grade and staging were reviewed.
      Immunohistochemistry and PCR were used to determine clonality. RESULTS: No
      significant differences were found between non-Hodgkin lymphomas and lymphoid
      hyperplasias, except for the mean age of the patients (6.3 years older in non
      Hodgkin lymphomas). In both groups the most common presentation was a mass with
      an indolent course; visual impairment was seen in 13%, conjunctival redness in
      25%, pain in 12%, and acute orbital inflammation in 15% of the patients. In most
      cases, the CT showed one or more lobulated or rounded masses, molding to adjacent
      structures, or a wedge-shaped enlargement of the lacrimal gland. Intramuscular
      lymphomas were rare and always associated with extramuscular masses. On T2
      weighted MRI, only 35% of lymphoid tumors were hyperintense. Only 49% of
      lymphomas were at stage I on presentation. CONCLUSION: An inflammatory
      presentation is not uncommon in orbital lymphoid tumors. Shape, molding and
      multiple masses can help radiological diagnosis, whereas MRI T2 intensity is
      unreliable. Accurate staging can disclose systemic disease in more than 50% of
      cases of non-Hodgkin lymphoma.

PMID- 8858357
TI  - Evaluation of two nonculture antigen tests and three serotests for detection of
      anti-chlamydial antibodies in the diagnosis of ocular chlamydial infections.
AB  - BACKGROUND: Diagnosis of chlamydial conjuctivitis is difficult in chronic
      diseases because chlamydial elementary bodies are mostly undetectable in
      conjunctival scrapings by cell culture. We therefore compared two nonculture
      antigen tests and three different serotests for anti-chlamydial antibodies with
      McCoy cell culture, the "gold standard" of chlamydial diagnosis. Conjunctival
      scrapings and serum samples of 93 patients attending the outpatient eye clinic in
      Graz because of chronic follicular conjunctivitis were tested. METHODS: A total
      of 558 conjunctival scrapings and 93 serum samples were investigated. Chlamydial
      antigen detection was done by McCoy cell culture, polymerase chain reaction (PCR;
      Amplicor, Roche), and direct immunofluorescence assay (DFA; Microtrak, Syva).
      Antichlamydial IgA and IgG antibodies in the sera were detected by an
      immunoperoxidase assay (IPAzyme, Savyon) and two different enzyme-linked
      immunosorbent assays (SeroELISA, Savyon and rELISA, medac). RESULTS: Cell culture
      and PCR yielded identical results. The positivity rate for chlamydial
      conjunctivitis was 8.6% (8 of 93 patients). PCR proved most sensitive and most
      specific. IPAzyme was 75% sensitive for IgA and 100% for IgG; SeroELISA and
      rELISA were less sensitive. IPAzyme was 81% specific for IgA and 47.3% for IgG.
      SeroELISA and rELISA were less specific for IgA, but more specific for IgG. Post
      test likelihood of disease was greatest in IPAzyme. CONCLUSIONS: PCR proved to be
      a good alternative to cell culture; DFA is useful for quick diagnosis. Genus
      specific serotests cannot compete with chlamydial antigen detection. They differ
      in sensitivity and specificity because of the antigen type they present. They are
      still of only supportive value in cases where chlamydial antigen detection is not
      possible. Recently introduced species-specific antibody tests should be of
      greater value.

PMID- 8858359
TI  - Employment of bioluminescence for the quantification of adenosine phosphates in
      the human cornea.
AB  - BACKGROUND: Quantification of adenosine phosphates in human corneal extracts has
      been performed using spectrophotometry. We employed the bioluminescence technique
      to obtain a more sensitive assay for adenosine phosphates and to reduce the
      volume of the test sample. METHODS: The bioluminescence assay for ATP, already
      known from sterility control, was modified and expanded. Standard curves were
      established using a standard solution with equimolar concentrations of ATP, ADP
      and AMP. To monitor the method, adenosine phosphates were measured in 35 human
      corneal extracts using both spectrophometry and bioluminescence. RESULTS: Linear
      standard curves ranging from 1 to 45 pmol were established. The two methods
      yielded comparable results despite the use of a basic dilution of 1:100 for the
      new technique. CONCLUSION: Bioluminescence provides a highly sensitive
      quantification of adenosine phosphates in the human cornea and facilitates an
      extremely detailed evaluation of the metabolic status of the cornea.

PMID- 8858358
TI  - Experimental intravitreous cysticercosis.
AB  - BACKGROUND: Cysticercosis is one of the parasitic diseases that most frequently
      affects the eye. The most common and severe manifestations of ocular infection
      are secondary to posterior segment involvement, which often leads to blindness
      and atrophy of the eye. The pathogenesis of ocular injury in this disease is
      poorly understood. The authors have developed an experimental animal model for
      intravitreous cysticercosis using New Zealand rabbits and Taenia crassiceps
      cysticerci. METHODS: Twelve rabbits were divided into two groups. Rabbits in
      group I were inoculated with one living cysticercus in the vitreous cavity.
      Rabbits in group II received an intramuscular dose of steroids prior to
      inoculation of parasites. RESULTS: An intense inflammatory reaction, which lead
      to a severe ocular injury, was observed in rabbits of group I, while rabbits in
      group II had minimal inflammatory changes. Histopathological studies showed a
      severe histiocytic infiltrate with generalized retinal damage in group I, and a
      mild inflammatory infiltrate, limited to the area of direct contact with the
      parasite in group II. The ocular lesions found in rabbits which did not receive
      steroids (group I) resembled those found in human ocular cysticercosis.
      CONCLUSION: These observations indicate that ocular damage in this parasitic
      disease might be directly related to inflammatory changes produced by the
      presence of cysticerci. This model appears to be useful for future
      investigations.

PMID- 8858360
TI  - Influence of physical exercise and nifedipine on ocular pulse amplitude.
AB  - BACKGROUND: Ocular pulse amplitude (OPA) was measured to investigate the
      influence of peripheral vasoconstriction and vasodilation on choroidal perfusion
      in healthy volunteers and to determine whether low OPA in low-tension glaucoma
      (LTG) patients is associated with a vasospastic reaction and its response to the
      calcium channel blocker nifedipine. METHODS: OPA was determined using the Langham
      ocular blood flow (OBF) system, applanation intraocular pressure (IOP), systemic
      blood pressure, and heart rate were measured, and ocular perfusion pressure was
      calculated before and after exercise and smoking in 12 otherwise nonsmoking,
      healthy volunteers and prior to and for 3 months after initiation of nifedipine
      therapy in 32 LTG patients with and without a vasospastic reaction as manifested
      by a nailfold capillary blood flow test. RESULTS: Exercise significantly (P <
      0.05) increased heart rate, systolic blood pressure and ocular perfusion
      pressure, while it significantly (P < 0.05) reduced IOP and diastolic blood
      pressure. However, OPA was not significantly (P > 0.1) affected by changes in
      these parameters. Smoking significantly (P < 0.05) increased systolic and
      diastolic blood pressure, heart rate, and ocular perfusion pressure but did not
      significantly (P > 0.09) alter OPA. There were two distinct LTG subtypes, with
      and without a vasospastic reaction. Only those with a vasospastic reaction showed
      a significant (P < 0.001) increase in OPA after 3 months of nifedipine treatment,
      while all other parameters tested were not significantly altered. CONCLUSION:
      Despite affecting ocular and systemic perfusion parameters, exercise and smoking
      did not alter OPA, suggesting functional isolation, i.e. autoregulation of the
      choroidal and/or ophthalmic artery circulation in healthy volunteers. Low OPA in
      LTG was increased by nifedipine only in vasospastic LTG patients, suggesting
      different, vasotonus-related pathologies. Calcium channel blockers and other
      vasodilators may be useful in vasoreactive LTG patients with reduced OPA.

PMID- 8858361
TI  - Multiple ocular impairment in a patient affected by Waldenstrom's
      macroglobulinaemia.
AB  - BACKGROUND: We studied a bilateral tumefaction of the lacrimal gland in a female
      patient. METHOD: Ocular and general clinical examinations were carried out.
      RESULT: Computerized tomography (CT) of the cranial orbit showed a tumefaction of
      solid density in the lacrimal gland. Histological examination of material removed
      by needle aspiration revealed the presence of elements of a lymphoplasmacytoid
      nature. Fluorescein angiography showed dilatation of the veins, intraretinal
      flame haemorrhages and small ischaemic areas. Chest CT showed an increase in the
      size of the middle and upper mediastinal lymph nodes, and examination of a
      specimen of bone marrow from the chest revealed the presence of small lymphocytes
      with a plasmacytoid tendency. CONCLUSION: On the basis of the findings, we
      diagnosed Waldenstrom's disease with rare multiple ocular impairment (lacrimal
      gland and retina) in an early stage.

PMID- 8858363
TI  - Immunogold silver staining for light microscopy.
AB  - The immunogold silver staining method (IGSS) is widely used as a sensitive and
      specific immunohistochemical visualisation technique. IGSS involves the specific
      deposition of metallic silver at the site of immunogold labelling and provides a
      means of visualisation at low magnification by light or electron microscopy.
      Silver developers for IGSS rapidly deposit metallic silver only at the site of
      heavy metals, including gold and silver, because of their catalytic activity. The
      developing solution contains the silver ions and reducing agent necessary for
      this reaction. Using different silver salts as ion donors and by selecting an
      appropriate temperature and pH, visible amounts of silver can be deposited in a
      few minutes at the site of colloidal gold labelling while little non-specific
      background deposition occurs. Inclusion of protective colloids in the solution
      can also be used to control the reaction. Although studies of the chemical basis
      of silver deposition around unlabelled colloidal gold date back to 1939,
      immunogold enhancement by silver was established in 1983. The IGSS method evolved
      from the combination of disparate photographic, histochemical and immunogold
      techniques which have been effectively combined and optimised over the last 10
      years to provide a visualisation system which is well suited to many
      immunohistochemical studies.

PMID- 8858362
TI  - The silver anniversary of gold: 25 years of the colloidal gold marker system for
      immunocytochemistry and histochemistry.
AB  - Since 1971, when W.P. Faulk and G.M. Taylor published "An immunocolloid method
      for the electron microscope", colloidal gold has become a very widely used marker
      in microscopy. It has been used to detect a huge range of cellular and
      extracellular constituents by in situ hybridization, immunogold, lectin-gold, and
      enzyme-gold labeling. Besides its use in light microscopic immunogold and lectin
      gold silver staining, colloidal gold remains the label of choice for transmission
      electron microscopy studying thin sections, freeze-etch, and surface replicas, as
      well as for scanning electron microscopy. The year 1996 is the 25th anniversary
      of the introduction of colloidal gold as a marker in immunoelectron microscopy
      and this overview outlines some of the major milestones in the development of the
      colloidal gold marker system.

PMID- 8858364
TI  - Freeze-fracture immunogold labeling.
AB  - Several approaches have been developed to combine immunogold cytochemistry and
      freeze-fracture techniques. These methods are highly heterogeneous regarding both
      the sequence of the procedural steps and the aspect of the resulting images. They
      imply immunolabeling either before or after freeze-fracture or even
      immunolabeling of platinum/carbon replicas of the freeze-fractured membranes, and
      have been used alternatively or in parallel to address different questions
      related to cell membrane structure, composition and dynamics or to intracellular
      membrane traffic. This review will briefly describe these methods and report most
      of their immunogold cytochemical applications, with the aim of facilitating
      selection of the most appropriate approach.

PMID- 8858365
TI  - Immunogold labeling in scanning electron microscopy.

PMID- 8858366
TI  - Improving structural integrity of cryosections for immunogold labeling.
AB  - Cryosections of aldehyde-fixed material prepared according to Tokuyasu are a good
      substrate for immunocytochemistry. However, structural defects occur that limit
      the resolution of this approach. We found that the step during which sections are
      thawed and transferred from the cryochamber to the supporting film on an EM grid
      is most critical for structural preservation. Surface tension of the transfer
      medium, on which sections are spread during thawing, can easily damage their
      structure by overstretching. By substituting a mixture of methylcellulose and
      sucrose for the conventional sucrose transfer medium, we were able to alleviate
      the problem of overstretching, thus improving greatly the structural integrity of
      thin cryosections. Also, material extraction from the sections after thawing
      causes structural damage, particularly when cross-linking is deficient.
      Incorporation of uranyl acetate in the transfer medium can then further help to
      maintain the structural integrity of the sections during the immunolabeling
      procedure. Excellent ultrastructure was featured in sections picked up and dried
      directly in methylcellulose/uranyl acetate mixtures. Such preparations can
      provide new insight into subcellular details and is an efficient back-up for
      immunolabeled sections in respect of their morphology. Cryosections from fresh
      frozen tissue can be preserved for immunolabeling by using transfer media that
      contain fixatives. This approach may have advantages if chemical fixation of
      tissue is thought to induce morphological artifacts or antigen redistribution.

PMID- 8858367
TI  - Non-isotopic electron microscope in situ hybridization for studying the
      functional sub-compartmentalization of the cell nucleus.
AB  - Post-embedding electron microscope in situ hybridization using gold particles as
      label permits the clear identification of the cellular structures which contain
      the nucleic acid molecules under study. It has yielded information on the
      distribution of defined nucleic acid sequences of different origins-cellular or
      viral, DNA or RNA, single- or double-stranded molecules-which has revolutionized
      the study of the nucleus. Application of this powerful technique in combination
      with other refined techniques to studies on transcription and replication of
      cellular and viral genes has augmented our knowledge of the functional
      organization of the cell nucleus. One can now ask mechanistically meaningful
      questions concerning the successive steps of gene replication and expression not
      only under normal conditions of cell growth, but also when the cellular
      metabolism is altered by a drug treatment or a viral infection. This chapter aims
      (a) to present the established methods of post-embedding electron microscope in
      situ hybridization for localizing, precisely and specifically, a nucleic acid
      target in its normal environment and (b) to present some contributions of this
      technique to investigations of the functional compartmentalization of the cell
      nucleus and to elucidate the cell-virus relationships in infected cells.

PMID- 8858369
TI  - Immunogold labelling of neuroendocrine peptides with special reference to
      antibody specificity and multiple staining techniques.
AB  - Immunogold methods have been very important for research on the neuroendocrine
      system. The compatibility of immunogold probes with optimal contrasting for
      electron microscopy has made localizations of neuroendocrine peptides to
      different subtypes of secretory organelles possible and, currently, methods using
      covalent attachment of nanogold particles to antibodies and neuropeptide ligands
      hold promise for immunocytochemistry, receptor localizations and in situ
      hybridizations. Multihormonal phenotypes are a hallmark of both the developing
      and mature neuroendocrine system. The possibility to localize multiple coexisting
      messengers by multilabelling immunogold methods is emphasized, and different
      methods for achieving this are discussed. The most difficult part of
      immunocytochemistry involves definitions and interpretations of specificity, and
      a number of limitations and control procedures are discussed.

PMID- 8858368
TI  - Protein glycosylation in the endoplasmic reticulum and the Golgi apparatus and
      cell type-specificity of cell surface glycoconjugate expression: analysis by the
      protein A-gold and lectin-gold techniques.
AB  - High resolution immunolabeling applying the protein A-gold technique and
      carbohydrate cytochemistry using lectin-gold labeling on Lowicryl K4M and thawed
      frozen thin sections are most useful approaches for the detection of protein
      antigens and lectin binding sites in intracellular organelles and the plasma
      membrane. They provided the basis for modern electron microscopic studies on
      protein glycosylation reactions and the identification of their subcellular
      localization as reviewed here. These studies have demonstrated organelle
      subcompartments and the cell type-specific compartmentation of endoplasmic
      reticulum and Golgi apparatus-associated glycosylation reactions. The other
      subject reviewed in this paper is cell surface glycoconjugates, as they are
      expressed in relation to specific cell types present in various organs and during
      cellular differentiation processes.

PMID- 8858371
TI  - Immunogold labeling of yeast cells: an efficient tool for the study of protein
      targeting and morphological alterations due to overexpression and inactivation of
      genes.
AB  - Immunogold labeling on Lowicryl HM20 resin sections is a valuable complement to
      biochemical methods as well as methods of molecular biology in the study of basic
      mechanisms in the yeast system. This contribution presents an overview of the
      state of the art. Emphasis is put on the explanation of caveats and pitfalls
      rather than on detailed bench protocols. In the Applications section the
      morphological aspect of genetic manipulation is accentuated and links to human
      pathology are indicated. The morphological consequences of genetic manipulations
      may gain importance in view of the efforts made to establish gene therapies. In
      particular, the contribution of immunoelectron microscopy to the elucidation of
      peroxisomal targeting signals and to the detection and identification of
      morphological alteration due to overexpressed, mutated or deleted genes in the
      context of peroxisome biogenesis is described.

PMID- 8858370
TI  - Contributions of the immunogold technique to investigation of the biology of
      peroxisomes.
AB  - The immunogold labeling technique has been extremely useful in investigation of
      the structure and function of peroxisomes. In this report a few examples of the
      application of this technique with significant implications in the field are
      briefly reviewed. The problem of extra-peroxisomal catalase, the subject of long
      controversy between the biochemists and cytochemists, was settled with the
      immunogold technique, which unequivocally revealed the presence of that enzyme
      not only in the cytoplasm, but also in the euchromatin region of nucleus, in
      addition to peroxisomes. On the other hand, lactate dehydrogenase, a typical
      cytoplasmic protein, has also been shown recently to be present in peroxisomes
      and to be involved in the reoxidation of NADH produced by the peroxisomal beta
      oxidation system. The immunogold technique has revealed several distinct
      compartments in the matrix of mammalian peroxisomes: urate oxidase in the
      crystalline cores, alpha-hydroxy acid oxidase B in the marginal plates and D
      amino acid oxidase in a non-crystalline condensed region of matrix. The specific
      alterations of peroxisomal proteins are reflected in their immunolabeling density
      with gold particles. Quantitation of gold-label by automatic image analysis has
      revealed that the induction of lipid beta-oxidation enzyme proteins by diverse
      hypolipidemic drugs is initiated and more pronounced in the pericentral regions
      of the liver lobule. Finally, immunogold labeling with an antibody to 70 kDa
      peroxisomal membrane protein has identified a novel class of small peroxisomes
      that initially incorporate radioactive amino acids more efficiently than regular
      peroxisomes and thus may represent early stages in the biogenesis of peroxisomes.

PMID- 8858373
TI  - In-situ end labelling with bromodeoxyuridine--an advanced technique for the
      visualization of apoptotic cells in histological specimens.
AB  - The fragmentation of nuclear DNA is considered to be a biochemical indication of
      programmed cell death (PCD) in various tissues. Several light microscopical
      approaches have been employed for the visualization of such fragmentation and
      have used either in-situ nick end labelling (ISEL) or in-situ nick translation
      (ISNT) with labelled dUTP. In the current paper, we can report a new method in
      which 0.5 micron Epon sections of mouse jejunum were incubated with terminal
      deoxynucleotidyl transferase (TdT) and 5-bromo-2-deoxyuridine (BrdU) for the in
      situ tailing of fragmented DNA. Anti BrdU and the peroxidase anti peroxidase
      method (PAP) were used for staining the reaction product. Semithin sections of
      jejunum revealed high resolution images of labelled nuclei in the intestinal
      mucosa. An examination with confocal laser scanning microscopy indicated the
      differential distribution of immunoprecipitates in cellular nuclei, perhaps
      representing those distinct levels of DNA cleavage that may characterise the
      discrete stages of apoptosis. This new method is likely to offer new
      possibilities for the high resolution imaging of PCD, including the assessment of
      time courses and apoptosis statuses in histochemically characterized cells.

PMID- 8858372
TI  - Applications of immunogold and lectin-gold labeling in tumor research and
      diagnosis.
AB  - Immunohistochemistry and carbohydrate histochemistry have had an enormous impact
      on both tumor research and diagnosis. In particular, immunogold labeling has
      provided significant advantages over classical fluorescence and enzyme-based
      techniques. In light microscopy, the silver-intensified gold labeling has proven
      highly sensitive and precise in localization. In electron microscopy, the gold
      particle marker was a prerequisite for successful and unequivocal antigen
      detection in electron-dense cellular structures such as secretory granules. In
      this review we demonstrate the usefulness of light and electron microscopical
      gold labeling techniques as applied in tumor research and diagnosis. The examples
      include expression of beta-1,6 branches and specific sialoglycoconjugates in
      colon carcinoma, b-12 carbohydrate epitope in breast carcinoma, polysialic acid
      in neuroendocrine tumors of lung, adrenal and thyroid, as well as studies on
      proinsulin to insulin conversion in insulinomas. In addition, practical hints for
      prevention of background staining, tissue fixation, and silver intensification of
      gold labeling are given.

PMID- 8858374
TI  - Influence of feeding pattern on thyroid hormones in long-term food-restricted
      rats.
AB  - The effect of a long-term 50% food restriction on plasma thyroid hormone levels
      was studied in adult male rats, which received their reduced daily amount of food
      either as one meal or 5 different meals. Compared to controls, a long-term food
      restriction reduced total 24 h-mean plasma T4, T3 and TSH concentrations. The
      total T4 level was more reduced in rats fed their reduced ration in one meal than
      in rats given food in several meals. This resulted in a higher T3/T4 ratio in the
      former group of rats than in the other groups (free access to food; food in
      several meals). In the control group and in the food-restricted group receiving
      their food in one meal, significant diurnal variations in total T4, T3 and TSH
      levels were seen. The T3 rhythm was abolished in food-restricted rats receiving
      their food spread over several meals, but T4 and TSH rhythms were not. We
      conclude that total peripheral thyroid hormone levels infood-restricted rats are
      influenced, not only by the amount of food but also by the feeding pattern.

PMID- 8858375
TI  - Absence of circulating adrenal autoantibodies in adult-onset X-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (ALD) is a frequent cause of adrenal insufficiency
      in young-adult patients with Addison's disease. As the contribution of an
      autoimmune process in the destruction of steroid cells in ALD is unclear, the aim
      of the present study was to evaluate the occurrence of adrenal-, thyroid- and
      islet-specific and non organ-specific autoantibodies in adult ALD patients. In
      all 5 patients, Addison's disease was the first manifestation of ALD. None of the
      ALD patients were positive for adrenal cortex autoantibodies in an indirect
      immunofluorescence assay, or for 21-hydroxylase autoantibodies in a radiobinding
      assay with recombinant human antigen. Similarly, we found neither non-organ
      specific autoantibodies (such as anti-nuclear, anti-ribosomal, anti-mitochondria,
      anti-smooth-muscle, anti-liver/kidney microsomal or anti-reticulin
      autoantibodies), nor islet-cell antibodies or glutamic acid decarboxylase (GAD65
      or GAD67) autoantibodies, nor thyroglobulin autoantibodies in the sera of the 5
      ALD patients. Two out of five patients were positive for thyroid microsomal
      autoantibodies. One of the two latter thyroid antibody-positive patients had
      clinical symptoms of hypothyroidism, and the other presented high levels of
      circulating TSH but no clinical signs or symptoms of hypothyroidism. Our study
      demonstrates that adult ALD is not immediately associated with the presence of
      adrenal autoantibodies and suggests that adrenal insufficiency is not mediated by
      an autoimmune process in adult ALD patients.

PMID- 8858376
TI  - Morphologic and functional alterations of the thyroid gland in rabbits treated
      with lithium.

PMID- 8858377
TI  - Insulin resistance in non-obese hypertensive subjects--its role in free fatty
      acid metabolism.

PMID- 8858378
TI  - The minimum dose of acarbose suppresses triglyceride concentration in remnant
      like particles from fasted diabetic subjects.

PMID- 8858379
TI  - Chronic autoimmunity of type I diabetes.
AB  - A considerable body of data supports the hypothesis that type I diabetes is a
      chronic progressive autoimmune disorder. Individuals with very high probability
      of progressing to diabetes can now be readily identified. Assays for
      autoantibodies reacting with insulin (IAA), glutamic acid decarboxylase
      (GAD65AA), and the neuroendocrine tyrosine phosphatase ICA512/IA-2 (ICA512AA)
      allow for the identification of more than 95% of individuals developing type I
      diabetes. The expression of a single autoantibody does not indicate high risk for
      diabetes and in general, prediabetic individuals express a series of
      biochemically defined autoantibodies. Levels of such autoantibodies are usually
      stable over years of follow-up. Unusual variants of autoantibody expression (e.g.
      GAD-ICA with high titers of GAD65 autoantibodies as the sole autoantibody) have
      low prognostic significance. Given the presence of multiple autoantibodies, low
      first phase insulin secretion (following intravenous glucose) is the best
      predictor of time to diabetes onset. Measurement of autoantibodies can now be
      automated and applied to large populations such that screening and prediction in
      the general population is now feasible. We favor the hypothesis that insulin may
      be the primary autoantigen for type I diabetes, and therapies which after the
      immune response to insulin may lead to safe and effective preventive modalities.

PMID- 8858380
TI  - The etiology of insulin-dependent diabetes--insights from epidemiological
      studies.

PMID- 8858381
TI  - Epidemiology of insulin-dependent diabetes mellitus around the Baltic Sea. The
      DIABALT Study Group.
AB  - Great spatial variation in the incidence of IDDM is found among countries around
      the Baltic Sea, a relative small area on the global scale. We present recent data
      on IDDM incidence from countries around the Baltic Sea, monthly variation and
      time trends in incidence from the early 1980s to the early 1990s. The change in
      IDDM incidence was calculated from logarithms of incidence using linear
      regression. The incidence was high in the countries to the north and west from
      the Baltic Sea, being the highest in Finland (35 per 100,000/year) followed by
      Sweden (26), Denmark (22) and Norway (21). In the countries on the eastern and
      southern coast of the Baltic Sea the incidence was markedly lower, in Estonia the
      incidence (10) was the highest within these countries, though slightly less than
      one third of that in Finland, while it was in Lithuania 7, Latvia 7 and Poland 6.
      There was an increasing trend in incidence of IDDM in Finland, Norway and Poland.
      In Sweden the incidence increased from 1978 to 1984, but since then the trend has
      been flat. In Estonia, Latvia and Lithuania, no significant change in incidence
      was seen. The reasons for large differences observed in the incidence of IDDM
      between countries around the Baltic Sea area are unknown, but a complex
      interaction between genetic and environmental risk factors that can vary in
      different ethnic, socio-economic and cultural settings play an important role in
      this variation.

PMID- 8858382
TI  - Genetic and immunological findings in patients with newly diagnosed insulin
      dependent diabetes mellitus. The Swedish Childhood Diabetes Study Group and The
      Diabetes Incidence in Sweden Study (DISS) Group.
AB  - Two large population-based case-control studies are reviewed. The aim is to
      determine the effects of HLA, other genetic factors and immune markers (ICA, IAA
      and GAD65Ab) on the age at onset of insulin-dependent diabetes mellitus (IDDM) in
      0-34 year olds. The primary HLA risk gene sequence for IDDM was difficult to
      identify because of the low recombination frequency within the HLA region. The
      frequency of the DR3-DQA1*0501-DQB1*0201 haplotype and the DR3-DQA1*0501
      DQB1*0201 (DQ2)/DR4-DQA1*0301-DQB1*0302 (DQ8) genotype were higher among patients
      diagnosed before the age of 10 compared with those diagnosed after the age of 30.
      The negatively associated haplotype, DR15-DQA1*0102-DQB1*0602 was absent before
      the age of 10, but the frequency increased with increasing age at onset. The
      IDDM2 gene representing the variable number of tandem repeat (VNTR) sequences and
      5' of the insulin gene on chromosome 11 were associated with IDDM since
      homozygous short VNTR was positive but not homozygous, and heterozygous long VNTR
      was negatively associated with the disease. The diagnostic sensitivity and
      specificity of GAD65 (GA65Ab) and insulin (IAA) autoantibodies varied with the
      age at onset and gender. GAD65Ab had the highest sensitivity (> 80%) in patients
      older than 20 years of age with no difference in gender. The lowest sensitivity
      (54%) was in 0-10 year old boys, while age did not affect the sensitivity in
      girls. In contrast, the sensitivity of IAA was highest (46%) before the age of 15
      but decreased thereafter as did the sensitivity for ICA. Classification of
      patients who develop IDDM above 20-25 years of age was inadequate since many
      patients classified with NIDDM either had GAD65Ab or ICA or developed these
      antibodies after 1-2 years of NIDDM. We conclude that not only age but also
      gender affect the risk for IDDM associated with HLA, other IDDM genes as well as
      commonly used immunological markers for IDDM.

PMID- 8858383
TI  - Autoimmune (type 1) diabetes in young adults in Sweden.

PMID- 8858384
TI  - Autoimmune endocrine disease.
AB  - Endocrine cells may become targets for autoimmune processes resulting in cellular
      dysfunction and diseases which cause considerable morbidity. The thyroid
      follicular cells, the parietal cells of the gastric mucosa, the insulin-producing
      islet cells and the adrenal cortical cells are most often affected. This rank
      order may indicate a relationship between antigen mass and prevalence of disease
      in a given organ (15).

PMID- 8858386
TI  - T cell autoimmunity to glutamic acid decarboxylase in human insulin-dependent
      diabetes mellitus.

PMID- 8858385
TI  - Autoimmune polyendocrinopathy--candidiasis--ectodermal dystrophy (APECED).
AB  - APECED, an autosomal recessive disease manifests itself as a widely variable
      combination of three groups of components: 1) autoimmune destruction of tissues,
      predominantly endocrine glands, 2) chronic superficial candidiasis, and 3)
      ectodermal dystrophy. Clinical and basic information obtained from Finnish series
      of 72 patients is reviewed.

PMID- 8858387
TI  - Nicotinamide: potential for the prevention of type 1 diabetes?

PMID- 8858388
TI  - Intracavernous pharmacotherapy: comparison of Moxisylyte and prostaglandin E1.
AB  - We report in this retrospective study the results obtained with the first two
      drugs proposed to reduce the relatively high rates of priapism and fibrosis bound
      to the papaverine intracavernous injections, i.e. the alpha-blocking agent
      Moxisylyte (Mox), and prostaglandin E1 (PGE1). Each drug was used for auto
      injections in 130 patients with a comparable mean follow up (14.8 months with Mox
      compared to 14.6 with PGE1). PGE1 proved to be significantly more efficacious
      (good results in 71% of the patients vs 50% with Mox), especially in the
      arteriogenic patients (respectively 96% vs 46%). Conversely PGE1 induced
      prolonged erections in significantly more patients (11 vs 1 with Mox), including
      2 priapisms, and also induced pain in more patients (12 vs 1 with Mox). The rate
      of fibrotic nodules and plaques was low (2 and 3 patients). Despite the better
      tolerance of Mox, its continuation rate was significantly lower than that of
      PGE1, PGE1 can be the first choice agent in most cases. Mox is mainly indicated
      in the patients with supersensitivity to the injections and in those with
      significant pain following PGE1.

PMID- 8858390
TI  - Self-injection devices for intracavernosal pharmacotherapy: operational
      classification and safety considerations.
AB  - Several self-injection devices have been recently proposed as an aid to home
      intracavernosal self-injection treatment for erectile dysfunction, with the
      purpose of allowing an easier drug administration, decreasing the artificiality
      of intracavernosal pharmacotheraphy, with the overall goal of increasing the
      acceptability of this treatment. We propose a classification of these devices
      according to the type of mechanical impact on the cavernosal tissue: self
      injection pens, allowing for manual needle insertion and manual drug delivery;
      autoinsertors, with automatic needle insertion and manual drug delivery, and
      autoinjectors, that provide both automatic needle insertion and automatic drug
      delivery. The use of autoinjectors bears two theoretical risks: extra-corporal
      drug delivery in cases of wrong injection site, and trabecular damage due to high
      delivery pressure. In one device pressures 15 times higher the values reached by
      manual injection, and statistically higher than pressures obtained by maximal
      strength manual injection, were observed in an in-vitro investigation. Specific
      studies are needed to define a threshold pressure value for trabecular damage in
      the flaccid state; accordingly, information on autoinjector developed pressures
      should be provided by manufacturers. Clinical studies with adequate follow-up are
      needed as well, to verify the risk of autoinjector-induced extracorporal drug
      delivery, and the occurrence of intracavernosal nodules or penile curvature,
      compared to manual self-injection.

PMID- 8858389
TI  - Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase
      inhibitor for the treatment of penile erectile dysfunction.
AB  - Sildenafil (Viagra, UK-92,480) is a novel oral agent under development for the
      treatment of penile erectile dysfunction. Erection is dependent on nitric oxide
      and its second messenger, cyclic guanosine monophosphate (cGMP). However, the
      relative importance of phosphodiesterase (PDE) isozymes is not clear. We have
      identified both cGMP- and cyclic adenosine monophosphate-specific
      phosphodiesterases (PDEs) in human corpora cavernosa in vitro. The main PDE
      activity in this tissue was due to PDE5, with PDE2 and 3 also identified.
      Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In
      human volunteers, we have shown sildenafil to have suitable pharmacokinetic and
      pharmacodynamic properties (rapid absorption, relatively short half-life, no
      significant effect on heart rate and blood pressure) for an oral agent to be
      taken, as required, prior to sexual activity. Moreover, in a clinical study of 12
      patients with erectile dysfunction without an established organic cause, we have
      shown sildenafil to enhance the erectile response (duration and rigidity of
      erection) to visual sexual stimulation, thus highlighting the important role of
      PDE5 in human penile erection. Sildenafil holds promise as a new effective oral
      treatment for penile erectile dysfunction.

PMID- 8858391
TI  - The post-investigation questionnaire (PIO-R): a practical instrument to assess
      erectile response after intracavernous injection.
AB  - Erectile response to intracavernous pharmacological stimulation is highly
      susceptible to stress and anxiety provoked by the test-situation. To reduce false
      positive diagnosis of veno-occlusive dysfunction and to limit the need for high
      dosage pharmacotesting, we developed the Post-Investigation Questionnaire (PIQ
      R), a self-report instrument to assess erectile response to pharmacological
      stimulation after the patient has left the office. In this study veno-occlusive
      sufficiency was not demonstrated in 80 of 105 patients with erectile dysfunction
      at the time of pharmaco-penile duplex ultrasonography. PIQ-R detected sufficient
      erectile response in 40 of these patients, thus reducing false-positive diagnosis
      of veno-occlusive dysfunction by 50%. We also found that reports of sexual
      activity after investigation increased interest in auto-injection therapy. PIQ-R
      is a practical self-report measure to assess erectile response after clinical
      pharmacotesting, and to more carefully select patients for auto-injection
      therapy.

PMID- 8858392
TI  - Compliance to longterm vasoactive intracavernous therapy.
AB  - From December 1986 to December 1991, 107 patients with organic impotence were
      advised to intracavernous pharmacological therapy with papaverine. Sixteen
      patients refused such treatment: 91 patients, after the determination of the
      therapeutical dose, underwent self injection. The follow up was 30-90 months.
      Thirty-seven patients (40.7%) withdraw the treatment within 3 months: 3 patients
      (3.3%) after losing the partner; 9 (9.9%) for intercurrent disease; 23 (25.3%)
      were unsatisfied for the therapy; 2 (2.2%) regained spontaneous erections.
      Complications were: local haematomas in 23 (42.6%); prolonged erections in 6
      (11.1%); fibrotic changes of the corpora cavernosa in 9 patients (16.7%); liver
      enzymes changes in 2 (3.7%). The reasons for the low compliance to the
      intracavernous pharmacological therapy with papaverine were analysed.

PMID- 8858393
TI  - Polyneuropathy in impotence.
AB  - Three hundred and forty-one consecutive impotent patients were evaluated for the
      presence of polyneuropathy (PNP) by neurophysiological and psychophysical tools,
      including nerve conduction and quantitative sensory tests (thermal and
      vibratory). PNP was present in 38% of diabetics, and 10% of non diabetics.
      Overall, PNP was found in 19% of impotent patients. PNP is relatively common
      among impotent patients, and might play a causative role. Patients judged
      'neurogenic' and those judged 'vasculogenic', based on nocturnal tumescence test
      (NPT) and vasoactive drug injection tests, had very similar rates of PNP (21 and
      23%, respectively). Thus it is suggested that the vasoactive drug injection test
      does not serve in discriminating neurogenic from non-neurogenic impotence. NPT,
      however, faithfully discriminates psychogenic from organic impotence, as far as
      PNP is involved, since a very low percentage of patients with normal NPT had PNP.

PMID- 8858394
TI  - Identification of a down-regulated mRNA transcript in corpus cavernosum from
      diabetic patients with erectile dysfunction.
AB  - Fifty per cent of men with diabetes have erectile dysfunction. Previous studies
      demonstrated that cultured smooth muscle cells from corpus cavernosum display
      significantly altered K+ channel function, PGE-induced cAMP accumulation, and
      endothelin-1 induced Ca2+ mobilization that are consistent with the
      pathophysiology of erectile dysfunction. Since defects in signal transduction
      frequently lead to altered gene expression, we examined differences in gene
      expression in corporal tissue excised from three diabetic patients with erectile
      dysfunction function and one patient with neurogenic erectile dysfunction. Using
      differential display, we identify a transcript expressed in tissue derived from
      the patient with impotence secondary to a radical prostectomy, but which was
      greatly reduced or absent in corporal tissue from all three diabetic patients
      examined. DNA sequence analysis indicates that this transcript has no significant
      homology to sequences presently deposited in the GenBank database. This suggests
      that altered gene expression may play a significant part in the etiology of
      erectile dysfunction.

PMID- 8858395
TI  - A consensus on the normal characteristics of corpus cavernosum EMG.
AB  - Corpus cavernosum EMG (CC-EMG) has raised much controversy since its
      introduction. The first workshop on CC-EMG has resulted in acceptance of a
      standardized technique of recording. Using this technique 110 normal potent
      volunteers have been examined in different centres. One year later there is an
      agreement among participants that an analogous recording of CC-EMG during
      flaccidity in normal subject results in reproducible findings. CC-EMG is
      characterized by highly reproducible waveforms (potentials) within the individual
      subject and mostly of comparable shape interindividually. Maximum peak to peak
      amplitude lies between 75 and > 500 microV and potentials have a mean duration of
      12 s.

PMID- 8858396
TI  - AMS 700 CX inflatable penile implants for Peyronie's disease: functional results,
      morbidity and patient-partner satisfaction.
AB  - This study was designed to clarify the functional results, morbidity and the
      patient-partner satisfaction observed with, the American Medical System 700 CX
      three-piece inflatable prosthesis in the treatment of impotence associated with
      Peyronie's disease. Thirty-three patients were treated and additional plaque
      surgery was performed in 13 cases (40%). Within 10 days of surgery, four patients
      (12%) developed a wound infection which was treated conservatively and one
      patient (3%) experienced glandular ischemia. At the 6-week follow-up, complete
      penile straightening was achieved in 23 patients (70%), while penile rigidity was
      considered optimal by all patients. On the contrary, the penis was considered
      short by 10 patients (30%). Five diabetic patients (15%) complained of severe
      scrotal and penile pain during full activation of the implant and in one of these
      patients (3%) the implant had to be removed. Due to spontaneous erections
      occurring after implant activation one patient (3%) required replacement of the
      reservoir from the Retzius space into the peritoneum. At the long-term follow-up
      (mean +/- SE: 17 +/- 2.2 months), 23 patients were evaluated and all found to be
      engaging in intercourse with the prosthesis. However, five patients (21%) and
      three of the 13 partners (25%) assessed were not yet completely satisfied. The
      American Medical System CX700 inflatable penile prosthesis obtains complete
      penile straightening in 70% and rigidity in 100% of impotent patients with
      Peyronie's disease. Patients should be fully informed about possible surgical
      morbidity and actual post-operative penile length.

PMID- 8858397
TI  - Antibiotic prophylaxis in prosthetic penile surgery: critical assessment of
      results in 75 consecutive patients.
AB  - OBJECTIVE: Antibiotic prophylaxis in prosthetic surgery was administered
      prospectively according an original protocol. Routine pre-operative preparation
      included also scrupulous, repeated disinfection of the skin of the genital and
      perineal region. METHODS: Vancomycin 500 mg i.v. every 6 h on the day of surgery
      and gentamicin 1 mg/kg i.v. every 8 h on the day of surgery and for the following
      48 h were administered to 75 consecutive patients. Overall 87 prosthetic devices
      were implanted. The patients were evaluated at 6 weeks and at 6 months after
      surgery. RESULTS: No infection was observed. CONCLUSION: Support from this study
      to antibiotic prophylaxis in penile prosthetic surgery is uncertain. The
      importance of scrupulous routine pre-operative preparation is probably
      underestimated.

PMID- 8858398
TI  - The hemodynamics of erectile dysfunction following nerve-sparing radical
      retropubic prostatectomy.
AB  - OBJECTIVE: Despite the advent of the nerve-sparing radical retropubic
      prostatectomy (NSRRP) a significant number of men still suffer from post radical
      prostatectomy impotence. The purpose of this study was to investigate the
      pathogenesis of erectile dysfunction following NSRRP and to define the previously
      reported vascular mechanism. Furthermore, it was our goal to clarify the
      respective contributions of arterial and venous components. PATIENTS AND METHODS:
      Sixteen potent males with localized prostate carcinoma underwent dynamic infusion
      cavernosometry preoperatively to assess arterial and venous hemodynamics. Ten of
      these men were impotent following the operation and had repeat cavernosometric
      evaluation six months postoperatively. RESULTS: On cavernosometry all 10 patients
      had arterial insufficiency on at least one side, six patients had bilateral
      changes. The mean reduction in CAOP was 50% (range 30-70%). Four patients met
      criteria for the diagnosis of corporovenocclusive dysfunction on cavernosometry.
      CONCLUSIONS: These data strongly support a vascular mechanism in the genesis of
      post-NSRRP impotence. This mechanism is predominantly arterial in nature, but
      some men have a mixed pattern with both arterial and venous components. The
      postoperative arterial insufficiency may be the result of intraoperative injury
      to the accessory pudendal artery. The exact means by which CVOD develops in this
      situation remains unclear at this time.

PMID- 8858399
TI  - Clinical practice guidelines for screening and monitoring male patients receiving
      testosterone supplementation therapy.

PMID- 8858400
TI  - Plasma and urinary markers of oral testosterone misuse by healthy men in presence
      of masking epitestosterone administration.
AB  - There is a potential need for the official criterion of testosterone abuse in
      sport (the urinary concentration ratio of testosterone
      glucuronide/epitestosterone glucuronide, TG/EG > 6) to be backed-up by some
      complementary markers, more particularly in cases of physiologically high TG/EG
      and when there is suspicion of joint administration of testosterone and
      epitestosterone. Testosterone, epitestosterone, their glucuro- and
      sulfoconjugates, 5-androstene-3 beta, 17 alpha-diol glucuronide and 17
      hydroxyprogesterone have been analysed by isotope dilution-gas chromatography
      mass spectrometry in plasma and urine of seven subjects supplemented with a
      single oral dose of undecanoates of testosterone and epitestosterone
      (respectively 40 mg and 1.5 mg). Adequate plasma criteria for testosterone abuse
      were the ratios of testosterone glucuronide/17-hydroxyprogesterone and
      testosterone glucuronide/testosterone which increased significantly above basal
      values for up to 10 h. The same trend was observed for the ratio of urinary
      glucuronides of testosterone/5-androstene-3 beta, 17 alpha-diol, while TG/EG was
      not affected by simultaneous administration of epitestosterone. One subject with
      low basal TG/EG failed to respond to testosterone administration by any
      significant increase of analysed parameters.

PMID- 8858401
TI  - Effects of prolonged L-carnitine administration on delayed muscle pain and CK
      release after eccentric effort.
AB  - Eccentric muscle effort is known to induce delayed muscle soreness (DOMS) and
      muscle damage which are not responsive to medical treatment with the most common
      analgesic agents. The aim of the study was to investigate the effects of oral L
      carnitine supplementation on pain (VAS scale), tenderness (pain thresholds) and
      CK release induced by a 20-min eccentric effort of the quadriceps muscle. A
      single-blind study was carried out on 6 untrained subjects (mean age: 26 +/- 3.8
      yrs; mean height: 173 +/- 4.6 cm; mean body weight, 68.3 +/- 4.5 kg) over 7 weeks
      during which each subject: a) was given 3 g/day of placebo for 3 weeks and, after
      a week's interval, 3 g/day of L-carnitine for 3 weeks: b) performed 2 step tests
      on the first day of the 3rd and 7th week inverting the order of the exercising
      limb. In a separate set of experiments carried out 8 months later, the possible
      effects of training on pain parameters and CK levels were also investigated in
      the same subjects who performed 2 step tests at a 4-weeks' interval, without
      medication. L-carnitine significantly reduced pain, tenderness and CK release
      after the effort with respect to placebo. In contrast, no significant difference
      was found in the parameters measured between the two tests performed without
      medication. It is concluded that L-carnitine has a protective effect against pain
      and damage from eccentric effort. This effect is mainly attributed to the
      vasodilatation property of the compound, which both improves energetic metabolism
      of the hypoxic/damaged muscle and enhances wash-out of algogenic metabolites.

PMID- 8858402
TI  - Relationships between exhaustive mood state and changes in stress hormones
      following an ultraendurance race.
AB  - To investigate how the pituitary-adrenal and sympathetic nervous hormones change
      in psychologically exhaustive states following an ultraendurance race, the
      Profile of Mood States (POMS), plasma ACTH, beta-endorphin, adrenaline,
      noradrenaline, and serum cortisol were measured in 29 male athletes two days
      before, immediately after, and one day after a triathlon. Psychological
      exhaustion was defined as possessing low POMS vigour and high fatigue immediately
      post-race. Eleven subjects met the criteria for the exhaustive group, and another
      ten were placed in the vigour group, which possessed high vigour regardless of
      fatigue score and the remaining eight subjects were excluded from analysis
      because they did not satisfy experimental protocol. Student's t-tests revealed no
      significant group differences in age, race time, pre-race POMS and hormone
      values. Immediately post-race, serum cortisol and plasma adrenaline did not
      differ between groups. However, significantly lower levels of plasma beta
      endorphin (p = 0.03) and noradrenaline (p = 0.05), and relatively lower levels of
      plasma ACTH (P = 0.08) immediately post-race were observed in the exhaustive
      group when compared with the vigour group. We conclude that pituitary and
      sympathetic nervous hormone reactivity is attenuated following ultraendurance
      race in athletes showing psychological exhaustion and this is independent of race
      performance.

PMID- 8858403
TI  - Comparison of exercise and normal variability on HDL cholesterol concentrations
      and lipolytic activity.
AB  - In order to compare the influence of a single bout of exercise on HDL-C
      metabolism with normal variability, 12 male runners (mean age: 24.9 +/- 4 yr) who
      ran 15-30 miles per week underwent exercise (E) and control (C) experimental
      conditions. During the E trial subjects ran on a motor driven treadmill at 75%
      (42.5 +/- 4.7 ml.kg-1.min-1) VO2max until 800 Kcals were expended. The C trial
      consisted of no exercise. Subjects were instructed to follow the same diet and
      keep a four d food diary during each experimental condition. Fasted blood samples
      were obtained at the same time of day in each condition at time points
      corresponding to 24 h pre-exercise (24 PRE), 6 h post- (6 h) and 24 h post
      exercise (24 h). Plasma was analyzed for HDL-C, HDL2-C and HDL3-C (mg.dl-1). In
      addition post-heparin plasma samples were analyzed for lipoprotein lipase (LPL)
      and hepatic lipase (HL) activity (mumol.FFA-1.ml-1). All values were adjusted for
      changes in plasma volume and compared to Baseline. HDL-C levels were unaltered
      following the C trial. However, following the E trial, HDL-C increased (p < 0.01)
      above baseline values at 24 h. The increase in HDL-C was reflected in the HDL3-C
      subfraction (p < 0.05). Analysis of lipolytic activity revealed an overall
      greater LPL activity (p < 0.05) in the E trial vs the C trial. In addition, a
      decrease in HL was observed at 24 h (p < 0.05) but was not different between
      experimental conditions. These data suggest that exercise and not normal
      variability are responsible for alterations in lipolytic activity and
      corresponding increases in HDL-C levels.

PMID- 8858404
TI  - Effects of unilateral concentric-only dynamic constant external resistance
      training.
AB  - The purposes of this investigation were to examine the effects of unilateral
      concentric-only leg extension dynamic constant external resistance (DCER)
      training on: (a) concentric DCER strength in the trained and contralateral
      (untrained) legs, (b) concentric isokinetic peak torque-velocity curves in the
      trained and contralateral legs, and (c) retention of concentric DCER strength and
      concentric isokinetic peak torque in the trained and contralateral legs following
      detraining. Sixteen adult male (mean age +/- SD = 24.0 +/- 4.0 yr) volunteers
      comprised training (TR, n = 8) and control (CTL, n = 8) groups. The TR group
      trained the nondominant limb with concentric-only leg extension DCER exercise (3
      5 sets of 6 repetitions at 80% of one-repetition maximum load) for eight weeks
      followed by eight additional weeks of detraining. The CTL group did not train.
      All subjects were tested pretraining, posttraining and detraining for unilateral
      concentric-only leg extension DCER strength as well as concentric isokinetic peak
      torque at 1.05, 2.09, 3.14, 4.19, and 5.24 rad.s-1 in both legs. Mixed factorial
      ANOVAs, follow-up, and post-hoc analyses indicated that the training resulted in
      increased DCER strength in both the trained (42%) and contralateral (15%) legs as
      well as isokinetic peak torque in the trained leg (7-19%) at velocities ranging
      from 1.05 to 5.24 rad.s-1. There was no cross-training effect, however, for
      isokinetic peak torque. Furthermore, the training-induced increases in DCER
      strength and isokinetic peak torque were retained across eight weeks of
      detraining.

PMID- 8858405
TI  - Inspiratory resistance effects on exercise breathing pattern relationships to
      chemoresponsiveness.
AB  - This study examined the effects of added inspiratory resistance (R5 5 cm H2O.L
      1.S-1) on the relationship between exercise breathing pattern and resting
      hypercapnic ventilatory responsiveness (HCVR). Twelve men completed an HCVR test
      and two progressive intensity exercise tasks with minimal (R0) and elevated (R5)
      resistance. Peak oxygen uptake, and peak power output were not different, but
      peak VE was decreased with the R5 load. Exercise ventilation (VE was tightly
      coupled to VCO2 (r = 0.97) as was mean inspiratory flow rate (VT/TI, r = 0.95),
      but not duty cycle (TI/TTOT, r = 0.39). With imposition of R5, VT/TI was
      depressed (p < 0.05) at mild (approximately 40% VO2peak) to peak exercise
      intensities, whereas TI/TTOT was relatively unaffected. At both moderate
      (approximately 60% peak VO2) and peak exercise intensities, VE was positively
      correlated (r = 0.62, p < 0.05 and r = 0.82, p < 0.01, respectively) to subjects'
      HCVR. However, when normalized, VE.VCO2(-1) was significantly correlated to HCVR
      only at peak exercise ventilation during the R0 load. Analysis of the exercise
      breathing pattern revealed that at both moderate and peak exercise intensities,
      VT/TI was positively correlated to HCVR, but TI/TTOT was not. The imposition of
      R5 decreased the slope of the relationship between exercise VT/TI and HCVR at
      both moderate and peak exercise intensities, and weakened the positive
      correlation at the moderate exercise intensity. Our analysis indicates that: 1)
      the positive correlation between exercise hyperpnea and HCVR is mediated by the
      mean inspiratory flow rate rather than the duty cycle component of the breathing
      pattern and, 2) at moderate exercise the relationship between mean inspiratory
      flow rate and resting HCVR is more sensitive to added inspiratory resistance than
      minute ventilation per se. These findings suggest that the degree of influence
      resting HCVR has on exercise hyperpnea is dependent upon the magnitudes of both
      the ventilatory hyperpnea and mechanical loading placed on the ventilatory
      system.

PMID- 8858406
TI  - Haemoconcentration in neurological decompression illness.
AB  - Decompression illness (DCI) is attributed to the formation of bubbles, resulting
      from the reduction of the ambient pressure. Circulating bubbles lead to capillary
      leak syndrome, extravasation of plasma and haemoconcentration. Experimental model
      on animals has shown that a haemoconcentration carried a poor prognosis. We
      measured the haematocrit level in fifty-eight consecutive sport divers, victims
      of neurological DCI, admitted to our hyperbaric center, and in sixteen control
      divers. No significant difference was found in the haematocrit values between the
      divers with neurological DCI (median 42.5%) and the controls (median 41.75%). The
      median haematocrit level was significantly higher for divers with neurological
      sequelae when compared with control (p = 0.01) or with divers without sequelae (p
      < 0.05). A haematocrit level > or = 48% was correlated with persistent
      neurological sequelae one month after the accident (p = 0.01). However, a
      haematocrit < 48% had no prognostic value.

PMID- 8858407
TI  - Is peak VO2 a maximal index of children's aerobic fitness?
AB  - A levelling of oxygen uptake (VO2 plateau) at high exercise intensities is
      conventionally used as the criterion for establishing VO2max during progressive,
      incremental exercise testing. Only a minority of children, however, demonstrate a
      VO2 plateau during exercise to voluntary exhaustion. This study was therefore
      designed to investigate whether a VO2 plateau is required before peak VO2 can be
      considered a maximal index of children's aerobic fitness. Eighteen girls and 17
      boys (age 9.9 +/- 0.4 yrs) carried out three treadmill tests to exhaustion one
      week apart. The first test comprised a discontinuous, incremental protocol to
      voluntary exhaustion. In test two each child warmed up and then ran to exhaustion
      at the same belt speed but on a gradient 2.5% greater than that which had
      produced an exhaustive effort on the first test. The third test was conducted
      similarly but the treadmill gradient was raised to 5% greater than that which had
      produced an exhaustive effort on the first test. Seven girls and 6 boys
      demonstrated a VO2 plateau (< or = 2 ml.kg-1.min-7) on the first test but no
      significant differences in either anthropometrical or peak physiological data
      were detected between those who demonstrated a plateau and those who did not.
      Mean peak VO2 values during tests two and three (supramaximal tests) did not
      increase significantly above that achieved on test one although indicators of an
      increased anaerobic contribution were significantly higher in both supramaximal
      tests. These findings indicate that peak VO2 in test one was a maximal value
      despite the absence of a VO2 plateau. The requirement of a VO2 plateau before
      peak VO2 can be regarded as a maximal index of young children's aerobic fitness
      is therefore untenable.

PMID- 8858408
TI  - Comparison of blood lactate concentrations obtained during incremental and
      constant intensity exercise.
AB  - Differences in blood lactate concentrations obtained during step-wise incremental
      and constant running exercise at the same intensities were investigated. In
      addition, the effect of endurance running at a constant intensity obtained by
      three different incremental modes (OBLA-4, 6 or 8 min) on the blood lactate
      concentration were studied. Eight firemen and six marathon runners performed: 1)
      three step-wise incremental running (IR) treadmill tests, each consisting of
      either 5 x 4, 5 x 6 or 5 x 8 min, and, 2) six 50 min constant intensity running
      (CR) treadmill tests. Capillary hemolyzed blood was used for lactate
      determination. The blood lactate during the 5 x 4 min IR-test was 32% (p < 0.001)
      lower for the firemen and 22% (p < 0.001) lower for the marathon runners compared
      with the steady state concentration. These differences were diminished in both
      groups when the 5 x 8 min IR test was used. In the marathon group, constant
      intensity running at the OBLA intensities obtained by the 5 x 4, 5 x 6 and 5 x 8
      min resulted in a lactate accumulation to a mean level of 8.1 mmol.I-1. Also, the
      marathon runners interrupted the exercise due to maximal perceived exertion after
      only 19 +/- 3, 26 +/- 4 and 30 +/- 6 min, respectively. In the firemen group, a
      majority of the subjects were able to complete the 50 min runs, despite a blood
      lactate accumulation to a mean level of 7.3 mmol.l-1 at the OBLA 5 x 4 and 5 x 6
      min intensities. When OBLA 5 x 8 min intensity was performed in this groups, a
      steady state blood lactate concentration to a mean level of 5.3 mmol.l-1
      occurred. It is concluded that step-wise incremental exercise with durations of 4
      or 6 min will lead to a high risk of overestimating the maximal lactate steady
      state exercise intensity and the endurance running capacity.

PMID- 8858409
TI  - The effects of pre-exercise starch ingestion on endurance performance.
AB  - This study compared the physiological responses and performance following the
      ingestion of a waxy starch (WS), resistant starch (RS), glucose (GL) and an
      artificially-sweetened placebo (PL) ingested prior to exercise. Ten college-age,
      male competitive cyclists completed four experimental protocols consisting of a
      30 min isokinetic, self-paced performance ride preceded by 90 min of constant
      load cycling at 66% VO2max. Thirty min prior to exercise, they ingested 1 g.kg-1
      body weight of GL, WS, RS, or PL At rest, GL elicited greater (p < 0.05) serum
      glucose and insulin responses than all other trials. During exercise, however,
      serum glucose, insulin, blood C-peptide and glucagon responses were similar among
      trials. The mean total carbohydrate oxidation rates (CHOox) were higher (p <
      0.05) during the GL, WS, and RS trials (2.59 +/- 0.13, 2.49 +/- 0.10, and 2.71 +/
      0.15 g.min-1, respectively) compared to PL (2.35 +/- 0.12 g.min-1). Subjects
      were able to complete more work (p < 0.05) during the performance ride when they
      ingested GL (434 +/- 25.2 kj) or WS (428 +/- 22.5 kj) compared to PL (403 +/-
      35.1 kj). They also tended to produce more work with RS ingestion (418 +/- 31.4
      kj), although this did not reach statistical significance (p < 0.09). These
      results indicate that preexercise CHO ingestion in the form of starch or glucose
      maintained higher rates of total carbohydrate oxidation during exercise and
      provided an ergogenic benefit during self-paced cycling.

PMID- 8858410
TI  - The influence of starch structure on glycogen resynthesis and subsequent cycling
      performance.
AB  - The present study was designed to evaluate the influence of starch structure on
      muscle glycogen resynthesis and cycling performance. Eight male cyclists (22 +/-
      1 yr) completed an exercise protocol (DP) to decrease vastus lateralis glycogen
      concentration. This exercise consisted of 60 min cycling at 75% VO2max, followed
      by six 1-min sprints at approximately 125% VO2max with 1 min rest intervals. In
      the 12 hr after the exercise each subject consumed approximately 3000 kcal
      (65:20:15% carbohydrate, fat and protein). All of the carbohydrate (CHO) consumed
      was derived from one of four solutions; 1) glucose, 2) maltodextrin (glucose
      polymer), 3) waxy starch (100% amylopectin), or 4) resistant starch (100%
      amylose). Muscle biopsies were taken from the vastus lateralis muscle after DP
      and 24 hr later to determine glycogen concentrations. A 30 min cycling time trial
      (TT) was performed following the 24 hr post-DP muscle biopsy to examine the
      influence of the feeding regimen on total work output. The post-DP glycogen
      concentrations were similar among the four trials, ranging from 220.3 +/- 29.2 to
      264 +/- 48.3 mmol.kg-1 dry weight (d.w.) muscle. Twenty-four hours after DP,
      muscle glycogen concentration had increased less (p < 0.05) in the resistant
      starch trial (+90.8 +/- 12.8 mmol.kg-1 d.w.) than in the glucose (+197.7 +/- 31.6
      mmol.kg-1 d.w.), maltodextrin (+136.7 +/- 24.5 mmol.kg-1 d.w.) and waxy starch
      (+171.8 +/- 37.1 mmol.kg-1 d.w.) trials. There were no differences in total work
      output during the TT, or blood lactate concentration immediately following the TT
      in any of the CHO trials. In summary, glycogen resynthesis was attenuated
      following ingestion of starch with a high amylose content, relative to
      amylopectin or glucose; however, short duration time trial performance was
      unaffected.

PMID- 8858411
TI  - Vitamin C and common cold incidence: a review of studies with subjects under
      heavy physical stress.
AB  - Several studies have observed an increased risk of respiratory infections in
      subjects doing heavy physical exercise. Vitamin C has been shown to affect some
      parts of the immune system, and accordingly it seems biologically conceivable
      that it could have effects on the increased incidence of respiratory infections
      caused by heavy physical stress. In this report the results of three placebo
      controlled studies that have examined the effect of vitamin C supplementation on
      common cold incidence in subjects under acute physical stress are analyzed. In
      one study the subjects were school-children at a skiing camp in the Swiss Alps,
      in another they were military troops training in Northern Canada, and in the
      third they were participants in a 90 km running race. In each of the three
      studies a considerable reduction in common cold incidence in the group
      supplemented with vitamin C(0.6-1.0 g/day) was found. The pooled rate ratio (RR)
      of common cold infections in the studies was 0.50 (95% CI: 0.35-0.69) in favour
      of vitamin C groups. Accordingly, the results of the three studies suggest that
      vitamin C supplementation may be beneficial for some of the subjects doing heavy
      exercise who have problems with frequent upper respiratory infections.

PMID- 8858412
TI  - The effect of moderate aerobic training on lymphocyte proliferation.
AB  - The purpose of this study was to determine the effect of 12 wks of aerobic
      training on resting lymphocyte number and proliferation, and immunoglobulin and
      cytokine levels. Eleven college-aged males (training group = EX) performed 30 min
      of cycling at 75% of VO2peak, 3 days/wk with VO2peak assessment and blood samples
      taken at 0,8 and 12 wks. A group of 10 sedentary controls (CT) underwent the same
      testing protocol. Lymphocyte proliferation response to phytohemagglutinin (PHA)
      and pokeweed mitogen (PWM) was quantified as a stimulation index (SI) based on
      the ratio of stimulated versus control cultures, and as total counts per min
      (CPM). Immunoglobulin (Ig) levels (IgG, IgA, and IgM), and lymphocyte counts were
      also determined. There was a significant increase in VO2 in the EX group (41.0 +/
      1.8 vs. 46.3 +/- 1.4 ml.kg-1.min-1 pre and post training, respectively).
      Training had no effect on the PHA SI for the EX group (23.9 +/- 3.3, 27.7 +/-
      4.1, and 26.3 +/- 4.0 at 0, 8 and 12 wks, respectively), or the responses of the
      CT group (28.8 +/- 6.0, 23.9 +/- 3.1, and 30.6 +/- 4.3). No changes were observed
      for the PWM SI. Significant increases were observed in the CPM for both groups.
      No differences in the Ig or lymphocyte levels were found during the study. These
      data indicate that 12 wks of moderate endurance training did not alter resting
      immune function as determined by mitogen stimulated lymphocyte proliferation,
      total circulating lymphocytes, or Ig levels.

PMID- 8858413
TI  - Increased prolactin response to hyperoxia at rest and during endurance exercise.
AB  - Neuroendocrine responses were investigated in 8 male athletes before, during and
      after 60 min of bicycle ergometry at an intensity corresponding to 1.5 mmol/l
      blood lactate in an incremental bicycle test. Hyperoxic gas (HE: 100% O2),
      hypoxic gas (HO: 14% O2, 86% N2) or normoxic gas (NO) were inhaled continuously
      during exercise as well as for 30 min before and after. During exercise,
      prolactin (PRL) increased in HO while it did not change significantly in NO. Only
      HE induced a PRL increase (400%) during 30 min of rest before exercise. PRL
      decreased in HE during exercise but remained higher than in HO. Growth hormone
      (GH), ACTH and norepinephrine (NE) did not increase in a similar pattern during
      HE. In comparison to NO and HE, increase of NE, GH and ACTH was significantly
      higher in HO, NE declined significantly in HE before exercise. Our results
      demonstrate that only PRL is affected by acute exposure to hyperoxia. Changes in
      inhibition of the dopaminergic system might contribute to augmentation of PRL
      before exercise. The exact underlying mechanisms are yet unknown.

PMID- 8858414
TI  - Attention exercise physiologists.

PMID- 8858415
TI  - Overview: performance measures--the next generation.
AB  - Can our existing quality toolkit respond adequately to the unprecedented changes
      in the health care system? The guest editor highlights the lessons offered by the
      articles in the issue and reflects on the challenges in identifying performance
      measures and using the data for quality improvement.

PMID- 8858416
TI  - Improving performance with clinical decision support.
AB  - BACKGROUND: CADU/CIS (Clinical and Administrative Decision-support Utility and
      Clinical Information System) is a clinical decision-support workstation that
      allows large volumes of clinical information systems data to be analyzed in a
      timely and user-friendly fashion. CARE PROCESS MEASUREMENT: For any given
      disease, subgroups of patients are identified, and automated, customized
      "clinical pathways" are generated. For each subgroup, the best practice norms for
      use of test and therapies are identified. Practice style variations are then
      compared to outcomes to focus inquiry on decisions that significantly affect
      outcomes. CASE STUDY: INTESTINAL OBSTRUCTION: Graduate Health Systems, a
      multisite integrated provider in the Philadelphia area, has used CADU/CIS to
      improve quality problems, reduce treatment-intensity variations, and improve
      clinical participation in care process evaluation and decision making. A task
      force selected intestinal obstruction without hernia as its first study because
      of the related high-volume and high-morbidity complications. Use of a ten-step
      method for clinical performance improvement showed that the intravenous
      administration of unnecessary fluids to 104 patients with intestinal obstruction
      induced congestive heart failure (CHF) in 5 patients. Task force members and
      other practicing physicians are now developing guidelines and other interventions
      aimed at fluid use. Indeed, the task force used CADU/CIS to identify an
      additional 250 patients in one year whose conditions were complicated by CHF.
      CONCLUSION: A clinical decision support tool can be instrumental in detecting
      problems with important clinical and economic implications, identifying their
      important underlying causes, tracking the associated tests and therapies, and
      monitoring interventions.

PMID- 8858417
TI  - Improving hospital-acquired infection rates: the CDC experience.
AB  - BACKGROUND: The National Nosocomial Infections Surveillance (NNIS) System, begun
      in 1970 by the Centers for Disease Control to collect data on hospital-acquired
      infections, is one of the oldest continuously operating clinical performance
      indicator systems in the United States. Growth of the system, from 19 to 230
      hospitals, has been accompanied by developments such as the evolution from
      hospitalwide to targeted surveillance, improved data processing and
      telecommunications for data collection and reporting, and risk adjustment.
      ELEMENTS OF A SUCCESSFUL SYSTEM: The NNIS System provides specific, standardized
      methods for data collection and uses device-associated, device-day rates to risk
      adjust the data and make it meaningful for interhospital comparison. The system
      has been used as a tool for improving quality of care through prevention of
      nosocomial infections. For example, an 800-bed teaching hospital's rate of
      ventilator-associated nosocomial pneumonia in the surgical intensive care unit
      49.5 infections per 1,000 ventilator days-was in excess of the 90th percentile.
      Improvements in care, including changing tubing and cascades every 48 hours and
      Ambu bags every 24 hours, as well as increased clinical evaluation of patients,
      was followed 12 months later by a decrease to 25.8 infections, well below the
      90th percentile. INFORMATION DISSEMINATION: Since 1992, staff from NNIS hospitals
      have met in a biennial conference to learn about advances in nosocomial infection
      surveillance and to share information with one another on infection control and
      quality improvement programs. CONCLUSIONS: The NNIS experience can be used as a
      source of guidance for assessing the effectiveness and utility of other indicator
      systems.

PMID- 8858418
TI  - Adapting a statewide patient database for comparative analysis and quality
      improvement.
AB  - BACKGROUND: In 1991 the Michigan Health and Hospital Association established the
      Michigan Patient Outcome Measures Program to support quality improvement
      activities among member hospitals. Data submitted by each hospital are based on
      the Uniform Hospital Discharge Data Set (UHDDS). REPORTING THE MEASURES: Each
      participating hospital is provided with tabulations for each of the 18
      indicators, along with comparative data for each of five hospital peer groups.
      CASE STUDY 1: FACILITATING DEVELOPMENT OF A CLINICAL PATHWAY: Review of data on
      stroke patients indicated that patients discharged to home represented the single
      largest group of patients and that their length of stay was lower than for other
      groups of stroke patients. Hospital A used a clinical pathway to achieve
      reduction in length of stay of almost a day for this group. CASE STUDY 2:
      IMPROVING OBSTETRICS AND GYNECOLOGIC SERVICES THROUGH EDUCATION: The Department
      of Obstetrics and Gynecological Surgery at Hospital B achieved improvement in
      birth trauma, hysterectomy, cesarean section (C-section) births, and vaginal
      births after C-section. Program participants are considering adopting a birth
      trauma indicator. CASE STUDY 3: ESTABLISHING A HOSPITALWIDE QI PROGRAM: The
      Newborn Team at Hospital C initiated several QI initiatives aimed at reducing the
      newborn mortality rate, including guidelines for earlier identification of high
      risk obstetric cases and for earlier intervention by the perinatalogist.
      CONCLUSIONS: Data that are not risk or severity adjusted have value in assessing
      hospital procedures and systems and can be used to educate and effect change in
      practice patterns.

PMID- 8858419
TI  - Do performance indicators make a difference?
AB  - BACKGROUND: The Maryland Hospital Association, Inc (MHA) Quality Indicator (QI)
      Project, a program of indicator development and application, includes more than
      1,100 participating hospitals. Access to data is limited to participants to
      promote improvement through comparison across hospitals. Participating hospitals
      have identified and acted on opportunities for improvement in information
      systems, communication across departments and functions, processes of care,
      identification of appropriateness of practice, and improvement ?beyond the
      hospital door?. CASE STUDY 1: Two teams were formed to address waiting time in
      the emergency department and failure of patients to find treatment. Improvements,
      including rapid notification of available inpatient beds, additional staffing
      during high-census periods, and streamlined processes for lab work and imaging
      turnaround times, were followed by better indicator performance. CASE STUDY 2: A
      hospital discovered three causes for a high rate of unscheduled admissions
      following ambulatory surgery. Interventions included extending the hours of the
      Same Day Surgery Unit (to solve a urination problem) and changing the anesthesia
      used (to reduce nausea and vomiting). CASE STUDY 4: To successfully bring its
      cesarean section (C-section) rate down closer to the statewide rate, one hospital
      had physicians encourage patients with previous C-sections to undergo a trial of
      labor, promoted the use of epidural anesthesia, and took advantage of new
      packaging to facilitate the use of prostaglandin gel to induce cervical dilation.
      CONCLUSIONS: The QI Project continues to deal with issues concerning quality of
      data versus quality of care, the correlation between indicator rates and care
      processes, and the usefulness of severity adjustment.

PMID- 8858420
TI  - Using clinical and functional data for quality improvement in outcomes
      measurement consortia.
AB  - BACKGROUND: Using standardized measures, American Group Practice Association care
      providers compiled a national database from which patients could be tracked,
      allowing for epidemiologic comparisons among treatments, sources of care, and
      results. Within five years, the consortia expanded from 6 to 55 clinics and from
      a focus on total hip replacement surgery to eight different health conditions.
      DATA COLLECTION PROCESS: Reflecting areas of significant public concern, high
      prevalence, high cost, or research needs, both patient- and provider-source data
      are collected at group practices at standardized intervals: 6 months, 12 months,
      and annually thereafter. OUTCOMES DATA MANAGEMENT AND REPORTING: A readily
      adaptable database infrastructure allows data-collection tools to adapt
      individual questions to changing conditions in the health care environment while
      maintaining the integrity of the whole structure. Aggregate-level reports
      complement individual clinics' own internal analysis efforts by providing a
      context for the interpretation of results. CASE STUDIES: In a total hip
      replacement consortium (including more than 2,300 patients), early findings have
      shown that patients do not fully recover from surgery as quickly as they
      themselves anticipated. In the cataract consortium, data scores on near, distant,
      day, night, glare, and overall vision scales improve considerably after cataract
      surgery, giving clinics a new tool to monitor and improve performance. In the
      asthma consortium, one clinic reevaluated the distribution of peak flow meters
      and the reasons for their underuse after noting the low number of patients in the
      clinic that had peak flow meters. LESSONS LEARNED: Provider participation in
      study design, instrumentation, data analysis, and feedback is important, and
      physician buy-in and support are critical to the success of any outcomes
      initiative. Missing data are the greatest limitations of a longitudinal data set
      and are difficult to collect through follow-up. There is still much to be learned
      about what functional status and well being measures can show about the
      relationship between health care services and patient health.

PMID- 8858421
TI  - Applying performance measures to long-term care.
AB  - BACKGROUND: Nine nursing facilities in Mississippi participated in the American
      Health Care Association's Quality Indicator Index and Education (QUIIX-Ed)
      project to apply quantitative performance measurements to continuous quality
      improvement in long-term care. Begun in May 1994, with the first collection of
      performance measurement data in March 1995, the project used 15 measures of
      clinical care based on standardized assessments of resident conditions.
      METHODOLOGY: QUIIX-Ed assessed the impact of quality indicator information in
      nursing facilities based on Minimum Data Set resident assessments. Comparison
      reports allow each facility to profile its performance against that of other
      providers in the project. The project does not standardize the quality
      improvement process: the focus is on the incorporation of information into
      existing nursing care and quality improvement practices. OPERATIONAL ISSUES: Each
      month the facilities updated their quality indicator scores and exported those
      scores to a central database that aggregated scores to generate benchmarking
      statistics for each facility, including project medians, percentiles, and
      facility performance rankings. EXAMPLES: Two case studies on bedfast residents
      and restraint use illustrate the process of examining care issues identified by
      quality indicators, developing appropriate interventions, and evaluating the
      efficacy of the intervention. DISCUSSION: The limited intervention of introducing
      quantitative care measurements had a significant impact on resident outcomes and
      the nursing process. These measurements are readily incorporated into existing
      nursing practices and facility improvement efforts, regardless of the extent to
      which the quality improvement process has been developed.

PMID- 8858422
TI  - Putting it (performance measures) together: an interview with Jerod Loeb.
      Interview by Steven Berman.

PMID- 8858423
TI  - Pulling it all together: the importance of integrative research reviews and meta
      analyses in nursing.

PMID- 8858424
TI  - Does sharing a mother-tongue affect how closely patients and nurses agree when
      rating the patient's pain, worry and knowledge?
AB  - A convenience sample of 50 hospitalized patients who had experienced major care
      from two nurses, one of whom shared their mother-tongue (Arabic) and one of whom
      did not, were asked to rate, using 10-point visual analogue scales, their current
      pain, worry about their medical condition, and knowledge about the medical
      investigations carried out. The two nurses nominated by each patient were asked
      to rate their patient's pain, worry and knowledge using the same scales. Pain
      assessments by the three respondent groups did not differ significantly; but only
      nurses sharing a mother-tongue with the patient provided pain ratings which
      correlated significantly with those of their patients. Both groups of nurses
      consistently rated patients as being more worried and more knowledgable than
      patients rated themselves. Nurses, unlike patients, associated greater knowledge
      with greater worry. The limitations of the study undertaken are reviewed.
      Discussion centres on the implications of these findings for optimizing nursing
      care, including situations where nurse and patient do not share a cultural
      background and cannot converse readily.

PMID- 8858426
TI  - Patient compliance: recognition of factors involved and suggestions for promoting
      compliance with therapeutic regimens.
AB  - Patient compliance is paramount in the effectiveness of therapeutic regimens.
      Without compliance therapeutic goals cannot be achieved, resulting in poorer
      patient outcomes. The social and psychological factors thought to influence
      compliance are identified as (a) knowledge and understanding including
      communication, (b) quality of the interaction including the patient-provider
      relationship and patient satisfaction, (c) social isolation and social support
      including the effect of the family, (d) health beliefs and attitudes-health
      belief model variables, and (e) factors associated with the illness and the
      treatment including the duration and the complexity of the regimen. Noncompliance
      is a significant problem and a major challenge for the health care team.
      Practical advice is offered for nurses and other health care professionals to
      increase patient compliance with therapeutic regimens. These include factors
      involved in the patient-provider relationship, communication skills and
      information-giving, and the mobilization of existing social support networks.
      Further research is needed to provide more conclusive results into the factors
      involved in patient compliance and to test the effectiveness of compliance
      enhancing strategies.

PMID- 8858425
TI  - The development of the Pain Management Inventory for patients with arthritis.
AB  - The initial development of the Pain Management Inventory (PMI), a precise
      clinical index of pain management methods intended for use with patients with
      arthritis, is reported. The PMI differs from available instruments in its intent
      to assess specific methods that the individual is currently using for arthritis
      pain management and the perceived helpfulness of these methods, thus providing
      information to be used in combination with other clinical indicators for planning
      and evaluating ongoing pain self-management. Sixteen of 17 items, or methods,
      initially demonstrated content validity. Using methods appropriate for an index
      of independent items, psychometric testing with a sample of 82 persons having a
      primary diagnosis of osteoarthritis or rheumatoid arthritis then focused on
      estimating the construct validity and test-retest reliability of each item.
      Findings assist in better understanding how various methods relate to overall
      pain management when it is defined as successfully taking care of or handling the
      pain as viewed within a cognitive-behavioural framework. Findings suggest that
      there are eight items that represent valid and reliable pain management methods.
      These items should be used and evaluated with additional arthritis samples to
      determine whether the findings replicate.

PMID- 8858427
TI  - Female genital mutilation: an overview.
AB  - The literature on female genital mutilation (also known as female circumcision)
      within a feminist theoretical context is discussed. Issues of culture, politics
      and religion in the literature will be examined in relation to feminist thought
      and the paper will also assess the effects of female genital mutilation on
      women's health and status within developing societies. Parallels with other
      similar practices in developed and developing countries will be drawn and policy
      strategies discussed.

PMID- 8858428
TI  - Comfort and nurses' moral choices.
AB  - Caring has been advocated as integral to nursing ethics, and much theorizing has
      suggested that it may be a partial or the entire foundation for nursing's ethic.
      Yet few research studies have examined the practical expression of caring in the
      clinical setting. The author describes the concept of comfort as an aspect of
      care experienced by long-term care nurses in their daily practice related to
      moral choices. The design of the study was descriptive and qualitative. The
      sample consisted of 15 registered nurses who were participants in the author's
      previous study of moral certainty and uncertainty. Their responses to interview
      questions during the previous study suggested the topic for the present study. A
      semi-structured interview consisting of eight neutral open-ended questions was
      conducted with each participant. The findings suggest that long-term-care nurses
      function in the roles of mediator and communicator. In these roles, they try to
      meet a mental ideal of "good nursing practice'. They use multiple criteria on
      which to base their moral choices including comfort, their own and their
      residents. The author examines the providing and feeling of comfort as related to
      the nurses' moral choices.

PMID- 8858429
TI  - Entry to care: positive choice or fait accompli? developing a more proactive
      nursing response to the needs of older people and their carers.
AB  - A range of issues surrounding admission to either residential or nursing home
      care are considered from the perspectives of older people and their family
      carers. Drawing on the literature and a number of studies conducted by the
      authors, the processes and perceptions that shape and influence admission to care
      are identified. On the basis of the interaction of these factors a four-stage
      typology of admission is suggested: the positive choice, the rationalized
      alternative, the discredited option, and the fait accompli. The characteristics
      of each admission type are discussed and the implications for professionals,
      particularly nurses, working with older people and their carers are addressed.

PMID- 8858430
TI  - Illness careers: the chronic illness experience.
AB  - The provision of skillful psychosocial care to patients suffering from chronic
      illnesses starts with an appreciation of what it is like to live with a chronic
      condition. Definitions of self-esteem may be realigned when patients encounter a
      prolonged problem, and reliance upon professional help. Getting inside the
      experience of such illness may be key to understanding patient motivation,
      noncompliance with therapy and altered patterns of social engagement.
      Individuals' personal constructs may usefully then be used to explore the extent
      to which chronic illness sufferers share common problems and needs.

PMID- 8858431
TI  - The grief experience of older women whose husbands had hospice care.
AB  - Grief is a universal phenomenon, affecting every age and culture. However, the
      literature reveals that this concept is surrounded with ambiguity and conflicting
      research findings. There are few studies which focus on the grief of older
      widows, and none which focuses on the grief of older women whose husbands
      received hospice care. The purpose of this longitudinal study was to generate a
      conceptual definition and theory of grief for older adult women using grounded
      theory methodology. Informants comprised six older widows whose husbands were
      enrolled in a hospice programme in a southern metropolitan setting in the United
      States. Each informant was asked to respond to the initial question: "What is
      your experience in dealing with the loss of your husband?' Interviews were
      conducted in the widows' homes after the deaths of their husbands during the
      following three time frames of bereavement: 1-4 months, 7-10 months and 13-16
      months. Interviews were audio-taped, transcribed, coded and analysed using the
      constant comparative method. Oracle, a text-oriented database management computer
      program, was used to facilitate the creation, storage, coding, analysis and
      retrieval of data. Cross-comparisons of the findings from the three phases of
      data collection were made and these findings were compared with the literature.
      The following core concepts emerged from the data: "being aware', "experiencing
      distress', "supporting', "coping' and "facing new realities'. Core concepts were
      combined into a conceptual definition of grief and a grounded theory of grief of
      older adult women whose husbands experienced hospice care was developed. The
      results of this study expand our knowledge of the grief process of older widows
      whose husbands received hospice care and have implications for the development of
      effective bereavement intervention programmes.

PMID- 8858432
TI  - Using factor analysis to explore nurses' fear of AIDS in the United States of
      America.
AB  - The purpose of this study was to create a reliable research instrument to test
      the fear of AIDS (FOA) and to explore the dimension of FOA among nurses. We
      hypothesized that certain factors, such as physical closeness to AIDS patients or
      HIV-positive blood and nontolerance of homosexuals, increase fear of AIDS among
      nurses. A sample of 365 nurses in a mid-Atlantic state of the United States was
      surveyed with an 82-item Knowledge, Attitudes, and Practice (KAP) questionnaire
      to examine the fear of AIDS among nurses in the United States. Using correlation,
      item and factorial analysis, a 23-item FOA Scale II (alpha = 0.826) was created
      and seven FOA factors were identified. Factor analysis was used to help
      understand the dimensions of FOA as measured by FOA Scale II. Principal
      components analysis was used to analyse the correlation matrix because some items
      were on a five-point scale and some were on a three-point scale. The varimax
      rotation was used, because if one were to define dimensions then these dimensions
      should be as independent of each other as possible. The coefficient alpha of
      0.826 obtained from using FOA Scale II indicated that FOA could be considered to
      be a general factor; but the general factor could be exhibited through several
      avenues. It was determined that FOA could be represented by four or by seven
      dimensions, and if one uses the eigenvalue of 1 for a cut-off point then one
      would argue that there were seven factors. If one used the screen test, then one
      could assume that there were four factors of interest. Our decision for the
      analysis of this paper was to attempt the interpretation of the seven factors. We
      used both the factor loadings-the correlation of the item score with the linear
      combination-and the factor score coefficients (the weights of the items to form
      the linear combinations) to interpret the factor. The factor analysis thus seems
      to give insight into the dimensions of FOA as measured by FOA Scale II. Fear of
      AIDS seems to be exhibited in the following seven ways: (a) support for policies
      which would protect me from AIDS, (b) fear of contact with blood and bodily
      fluids of AIDS patient, (c) turning against those who have AIDS, (d) only care
      for those who deserve to be helped, (e)concern that I would have no help if I had
      AIDS, (f) concern about the financial burden of AIDS, and (g) loss of self-worth
      for one who has AIDS.

PMID- 8858433
TI  - Effects of group discussion and guided patient care experience on nurses'
      attitudes towards care of patients with AIDS.
AB  - Nurses with limited experience in caring for persons with AIDS (PWAs) were
      randomized into three groups receiving an educational session on universal
      precautions and (a) three group discussion sessions; (b) three sessions of caring
      for a PWA; or (c) assessment materials only. Both interventions were conducted by
      a nursing instructor experienced in care of PWAs and infectious diseases over a 3
      4 week period. Measures included instruments for assessing prejudicial attitudes
      towards homosexual PWAs, self-ratings of infectious disease knowledge, ratings of
      perceived comfort and confidence in caring for PWAs, and a measure of willingness
      to provide care to PWAs. Results showed no significant change in willingness to
      provide care over time in any of the groups. Multiple regression exploring
      predictors of willingness to provide care found only the measure of AIDS
      prejudice to be an independent predictor of willingness to provide care to PWAs 6
      months after completion of the intervention phase.

PMID- 8858434
TI  - Effect of preparatory information prior to elective total hip replacement on
      psychological coping outcomes.
AB  - The objective of this study was to evaluate the effects of preparatory
      information on psychological coping outcomes among total hip replacement (THR)
      patients. A quasi-experimental design within an ethnographic clinical context was
      used. Eighty-two healthy individuals, scheduled for elective THR were recruited
      for the study and nonrandom selection techniques were used. The subjects in the
      experimental group were given procedural, sensory and coping information relating
      to the whole surgical procedure of a THR. In addition, written information was
      given to support the verbal information. Subjects in the control group received
      only the advice and support that would routinely be given to THR patients by
      ward, medical and nursing staff. The main outcomes were measured using standard
      questionnaires, Hospital Anxiety and Depression Scale (HADS) measuring anxiety
      and depression, Rosenburg Self-Esteem Scale measuring self-esteem, and Health
      Illness Questionnaire measuring sense of control. Lastly, a Linear Analogue
      Coping Scale was developed and applied to assess a subject's personal perception
      of coping with a THR. Providing information had positive effects on the
      psychological coping outcomes measured. Subjects in the experimental group had
      significantly less anxiety and depression with a high self-esteem and sense of
      control. The Linear Analogue Coping Scale demonstrated a strong correlation
      between how subjects believed they were coping and that measured using the
      standard questionnaires. The study concluded that preparatory information of
      various types and in different forms appears to have positive effects on
      psychological coping outcomes for THR patients, which may have influenced
      postoperative recovery.

PMID- 8858435
TI  - The treatment of decubitus ulcers: a century of misinformation in the textbooks.
AB  - Decubitus ulcers are slow healing; in many cases they stagnate and fail to heal.
      Examination of the literature concerning decubitus ulcers reveals that there is a
      large body of treatments which have been suggested to stimulate the healing
      wound. This study examines the clinical effectiveness of the various treatments,
      and the scientific basis behind them. The treatments currently available are
      compared with those discussed in the literature over the last century, and common
      threads emerge which have a bearing on how literally one should accept the advice
      offered in current textbooks.

PMID- 8858436
TI  - Nurses' accounts of cardiopulmonary resuscitation.
AB  - The relationship between theory and practice has received considerable attention
      within the nursing literature. This paper uses qualitative data from debriefing
      interviews with nurses following episodes of cardiopulmonary resuscitation (CPR)
      to illustrate the complexities of translating sanitized theory into the messiness
      of practice. The interplay of affect and cognition on both learning from
      experience and on professional practice are explored. The feelings engendered by
      the CPR event and the labour required for their management form the second and
      major part of the paper. These are explored by examining the realities of a CPR
      event with its accompanying threat of death; success and failure, dignity versus
      indignity and the place of appropriate emotions throughout.

PMID- 8858437
TI  - Violence to staff in a general hospital setting.
AB  - The problem of aggression to staff in a general hospital was examined from the
      perspective of Poyner & Warne's (1986) model of workplace violence. A total of
      396 staff (39% response rate) provided information on their experience of
      violence in the past year and a subsample were additionally interviewed about
      their current levels of mental health (GHQ). Some 72 staff (21% of respondents
      had been physically assaulted and 90% of these assaulted staff worked beyond the
      accident and emergency department, e.g. in medical wards. Nurses were physically
      assaulted, threatened and verbally abused at higher rates than other
      professionals. Employee factors (younger age, shorter National Health Service
      experience and attendance at violence training) were significantly associated
      with assault (P < 0.05). Postoperative confusion, receiving treatment and delayed
      treatment were common precursors of aggression. Mental health was significantly
      worse amongst staff exposed to threats (P < 0.01). This exploratory study
      establishes that violence is a problem across a number of general hospital
      departments and occupations and we argue that effective training should be made
      more available for staff at risk of assault.

PMID- 8858438
TI  - Do clinical nurse specialists and nursing unit managers believe that the
      provision of quality care is important?
AB  - The nursing profession has a long tradition of evaluating the quality of its
      product in order to ensure that the best possible care can be given. However, in
      the climate of economic rationalism which prevails worldwide, it is possible that
      the emphasis on fiscal restraint has distracted nurses from their previous focus
      on quality. This paper discusses the findings of two research studies designed to
      determine the competencies expected of nursing unit managers and clinical nurse
      specialists. Discussion focuses specifically on their roles in the provision of
      quality care.

PMID- 8858439
TI  - Using Spradley: an ethnosemantic approach to research.
AB  - The purpose of this paper is to demonstrate the use of Spradley's (1979)
      Developmental Research Sequence (DRS) as a research method. In a recent study
      which I have carried out exploring the practice of expatriate nurses, I chose to
      use this method for data collection and analysis. One major reason for the choice
      was that as a method within the qualitative paradigm it offered an explicit,
      systematic and rigorous approach to the collection and collation of the research
      data. The aim of my study was to explore the common experience of expatriate
      nurses working in developing countries in primary health care and to identify the
      common values that influenced their practices. DRS utilizes an ethnoscientific
      approach which incorporates a systematic study of the way of life of an
      individual or a community or group of people, understood through the process of
      ethnosemantic analysis or the study of the meaning within language. Or more
      simply, it offers a way of understanding something of the reality of another
      person's experience from the way that he or she talks about it. A major
      assumption of the method is that cultural groups or individuals organize their
      knowledge and subsequent rules for behaviour on the basis of culturally
      designated similarities and differences. The paper sets out the DRS method using
      examples from my study. It provides an opportunity to share my experience of
      using this method with others.

PMID- 8858440
TI  - The relevance of health visiting policy to contemporary mothers.
AB  - This research project examines whether health visiting policy, which developed at
      the beginning of the twentieth century, is relevant to contemporary mothers.
      Although previous studies have looked at clients' perceptions of the health
      visiting service, the fundamental question of whether or not such provision is
      needed or wanted by mothers of today has not been addressed. This research
      provides evidence that a client-centred health visiting service is very relevant
      to the needs of contemporary first-time mothers and is a service which they
      greatly value.

PMID- 8858441
TI  - Nurse researcher: a study of a contradiction in terms?
AB  - Despite considerable top-down pressure and numerous professional body
      initiatives, a persistent shortfall in published nursing research has been noted.
      Numerous explanations have been put forward to account for this which implicate
      issues at both the individual/psychological and the structural/ organizational
      levels. However, one area which has not yet been properly addressed is that of
      role appropriateness, in that research skills and activities may be construed as
      being incompatible with the traditional role expectations and values of nursing.
      To test this proposition, two groups of qualifed nurses were each required to
      consider six descriptors of an imaginary nurse following the paradigm of Asch's
      (1946) seminal Central Trait Theory study. Of these, five adjectives were
      identical for both groups, but the sixth descriptor was manipulated, such that
      one group received "good clinician' and the other "good researcher'. The subjects
      then had to rate this imaginary nurse along each of 15 bipolar traits. The
      groups' ratings were compared using a series of unrelated t-tests. The results
      indicated that if a nurse was described as a good researcher she or he was also
      assumed to be more ambitious, a poorer communicator, less kind, stronger, more
      logical, more controlled, more confident, less popular, more ruthless, more
      rational and more analytical than if she or he was described as a good clinician.
      These findings suggest that the qualities attributed to a good nurse are
      dissonant with those attributed to a good researcher and, in this way, the mutual
      incompatibility of each role's requirements may serve as an obstacle to the
      development of research with nursing.

PMID- 8858442
TI  - Reforming the practice of nurses: decolonization or getting out from under.
AB  - The practice of nurses has been formed and informed by many disciplinary
      discourses. We argue that this leads to the subjugation and colonization of
      nurses' practices and the discipline. By debating and challenging current
      development in knowledge the opportunity is created for nurses to reform
      representations of our practices in a way that can privilege diversity,
      complexity and ambiguity. In particular, modernism and postmodernism are
      critiqued to highlight the impact of particular philosophical traditions on the
      practices of nurses.

PMID- 8858443
TI  - Living a caring presence in nursing: a Heideggerian hermeneutical analysis.
AB  - While the claim has been made that caring is the most important, central focus of
      nursing, often the meaning of caring presence in nursing and human caring in
      general is so deeply embedded in our consciousness and our cultural practices
      that its presence is invisible or taken for granted. The purpose of this
      Heideggerian hermeneutical study was to illuminate nurses' shared practices and
      common meanings of living a caring presence in nursing. Five nurses wrote a
      story, one they would never forget, of living a caring presence. The stories were
      analysed and interpreted against a background of Heideggerian philosophy to
      reveal the constitutive pattern, "caring as the presencing of being'. Meaning and
      complexity of the pattern were revealed in themes that illuminate and articulate
      the essence of nursing and the phenomenon of caring. Themes were: the
      timelessness and spacelessness of caring, creating home, and the call to care as
      the call of conscience. The results can help to answer the Heideggerian question
      of what a marginalized cultural practice like the profession of nursing can teach
      a levelling technological society about the meaning of being.

PMID- 8858444
TI  - Nurses' representations of the positive and negative features of nursing.
AB  - Nurses' representations of their work are defined as their cognitive 'work
      spaces', a theoretical concept derived from Newell & Simon's (1977) problem
      solving model and Lewin's (1935) concept of interacting positive and negative
      valences. Using a structural equation modelling technique, a network of positive
      and negative features in nurses' work spaces is described in patterns of response
      to a questionnaire eliciting nurses' ratings of their professional opportunities
      and difficulties. The modelling technique revealed the dominance of positive over
      negative features, and the overall significance of social recognition for
      encouraging nurses to remain in nursing. Comparative analyses revealed that
      dominant features of work space representations did not differ for nurses from
      four city and country hospitals, nor in relation to positions in the nursing
      hierarchy. The importance of understanding the perceptions of nurses is discussed
      in relation to changes and development in nursing as a profession.

PMID- 8858446
TI  - Reflection as infiltration: learning in the experiential domain.
AB  - This paper discusses part of an ethnomethodological study of a short, post
      registration course in communication in palliative care. The study describes the
      different perceptions, expectations and reflections of the participants and the
      facilitators as they engaged together in learning through role-play, simulated
      interviews with patients and discussion. The emotionally challenging nature of
      experiential teaching in palliative care appeared to present the facilitators of
      the course with a number of dilemmas. The facilitators' reflections upon these
      dilemmas appeared to lead them to develop a series of strategies in an attempt to
      resolve them. During the study it became clear that some aspects of these
      strategies were withheld from the participants. These strategies and the
      reasoning behind them are described together with the participants' response. The
      study demonstrates how the participants' reflections upon the facilitator-led
      exercises led them to infiltrate the strategies adopted by the facilitators. The
      purpose of these strategies and the significance of the participants' unearthing
      of them are interpreted within the conceptual framework of Schon's "reflective
      practitioner'. The findings are discussed in relation to current nurse education
      and the possible implications for curriculum planning and development.

PMID- 8858445
TI  - Criteria for concept evaluation.
AB  - One of the roles of qualitative enquiry is the utilization of qualitative methods
      for the development, refinement or modification of concepts. Yet, to date, there
      are no criteria for evaluating the adequacy of a concept. In this paper, the
      anatomy of a concept is presented, methods of concept analysis critiqued, and
      criteria for evaluation of the level of maturity of a concept suggested.
      Evaluation of criteria include assessment of: the definition of the concept, the
      characteristics of the concept, the conceptual preconditions and outcomes, and
      the conceptual boundaries. The authors argue that evaluation of a concept must
      necessarily precede concept development research (using a Wilsonian-derived
      method, a critical analysis of the literature, or qualitative enquiry) and
      precede more formal research procedures (such as operationalization or
      identification of the variables).

PMID- 8858447
TI  - An analysis and evaluation of Watson's theory of human care.
AB  - Despite a high priority placed on theory-testing in nursing, there continues to
      be minimal research undertaken which adequately tests nursing theories. A study
      was planned to contribute to theory-testing in nursing by testing an aspect of
      Watson's (1988) theory of human care. Watson essentially believes that nursing is
      an intersubjective human process and places a high value on the caring
      relationship between the nurse and the recipient of care. Before proceeding with
      the intended study, the following analysis and evaluation of Watson's theory
      presented here was undertaken, with guidance from a tool developed by Fawcett &
      Downs (1992). In this tool, the analysis identifies the concepts and propositions
      that make up the theory and the evaluation includes the criteria of significance,
      internal consistency, parsimony, testability and empirical adequacy of the theory
      being tested. Overall, this analysis and evaluation found two areas of Watson's
      work which were in need of further development.

PMID- 8858448
TI  - Job satisfaction and organizational characteristics: results of a nationwide
      survey of baccalaureate nursing faculty in the United States.
AB  - This study examines the relationship between job satisfaction of nursing faculty
      and the organizational characteristics of the institutions and nursing programmes
      in which they teach. A stratified random sample of 48 baccalaureate nursing
      programmes throughout the United States was selected for the study, of which 25
      (52%) of the programme deans agreed to participate. Two questionnaires were used
      in data collection: (a) The Job Descriptive Index (Revised), which was sent to
      576 nursing faculty at the participating programmes, resulting in 327 (57%)
      usable questionnaires; and (b) The Organizational Characteristics Questionnaire
      which was completed by the nursing programmes deans. Dimensions of job
      satisfaction measured were: work on present job, present pay, opportunities for
      promotion, supervision, coworkers and job in general. The organizational
      characteristics examined were: institutional control (public, private), size
      (student enrolment), nursing degrees offered, programmes offered (undergraduate,
      graduate), number of nursing faculty, number of nursing students, budget, tenure
      and salary. Although nursing faculty tended to be satisfied with their jobs,
      correlation and multiple regression analyses indicated weak to negligible
      relationships between job satisfaction and the organizational characteristics
      examined. Further study of the dimensions of job satisfaction within the academic
      environment is needed to understand the complexity of these relationships fully.

PMID- 8858449
TI  - Breaking the boundaries between nursing and sociology: a critical realist
      ethnography of the theory-practice gap.
AB  - This paper is a response to the challenges laid down by Hannah Cooke in a paper
      in the Journal of Advanced Nursing entitled "Boundary work in the nursing
      curriculum: the case of sociology' (Cooke 1993a). In her paper, Cooke noted that
      the outlook of nursing and sociology are inimicable because nursing's
      concentration on individuals is at variance with sociology's concern with wider
      social issues. We argue that it is possible for nursing research to give due
      attention to social structures without losing its focus on individuals. One
      methodology that could facilitate this broadening of nursing's epistemological
      boundaries is critical realist ethnography, which works under the assumption that
      the relationship between social structures and individual actors involves a two
      way process, in that while the enablements and constraints imposed by structures
      influence individual actions, those actions in turn either maintain or transform
      social structures. To demonstrate how such a methodology could be applied in
      nursing research, we work through a case study concerning the theory-practice
      gap, arguing that the gap is neither the result of clinicians' ignorance of nor
      antipathy to theory, but is largely generated by the lack of resources enjoyed by
      nurses, which in turn is a reflection of the social structure of capitalism
      within which nurses operate.

PMID- 8858450
TI  - Does the use of antimicrobial agents in veterinary medicine and animal husbandry
      select antibiotic-resistant bacteria that infect man and compromise antimicrobial
      chemotherapy?

PMID- 8858451
TI  - Is continuous infusion of beta-lactam antibiotics worthwhile?--efficacy and
      pharmacokinetic considerations.
AB  - The most important pharmacodynamic parameter for beta-lactam antibiotics has been
      shown to be the time above the MIC, which is used as an argument to administer
      beta-lactam antibiotics by continuous infusion. Studies in vitro and in
      laboratory animals comparing efficacy of continuous and intermittent infusion of
      beta-lactam antibiotics generally show continuous infusion to be more
      efficacious. While comparative trials in humans are scarce and a significant
      difference was only found in subgroup analysis in one study, several case-reports
      support the use of continuous infusion. Arguments in favour and against
      continuous infusion are discussed. Although dose-ranging studies have not yet
      been performed in humans, the results from in-vitro and in-vivo experiments
      indicate that 4 x MIC for the infecting bacterium would be the target
      concentration. Pharmacokinetic studies which have been performed in humans during
      continuous infusion show that serum concentrations can be predicted from total
      clearance or, using population pharmacokinetic modelling, the elimination rate
      constant as obtained during intermittent infusion. A nomogram is presented which
      allows calculation of the daily dose to obtain the target steady state blood
      concentrations suggested by the susceptibility of the infecting bacterium,
      usually 4 x MIC. For bacteria with a low MIC, the daily dose may be substantially
      lower than that used in conventional dosing regimens, while in infections which
      are difficult to treat as a result of more resistant bacteria, continuous
      infusion may be more effective than an equivalent bolus dose.

PMID- 8858452
TI  - Fixed or variable concentrations of beta-lactamase inhibitors in in-vitro tests?

PMID- 8858453
TI  - Critical appraisal of E test for the detection of fluoroquinolone resistance.
AB  - The ability of E test to accurately detect fluoroquinolone resistance was
      compared with an agar dilution reference method. Nearly 300 isolates belonging to
      26 different species (62.5% with documented ciprofloxacin resistance) were tested
      with ciprofloxacin, fleroxacin, levofloxacin, norfloxacin, ofloxacin, and
      sparfloxacin. In contrast to earlier reports, E test MIC values for pneumococci
      and all rapid growing aerobes were routinely higher (approximately 0.5 log2
      dilution step) than agar dilution results. The E test stable-gradient method also
      efficiently identified fluoroquinolone-resistant subpopulations which were not
      detected by the reference procedure with the standard inoculum. Categorical
      agreement for 1710 test comparisons was approximately 90% with no very major,
      false-susceptible errors. We found the E test to be a valid, reproducible method
      for fluoroquinolone susceptibility testing that provided quantitative results and
      produced a conservative (1.6% false-resistant results) assessment of
      susceptibility of bacteria including isolates of Streptococcus pneumoniae and
      Pseudomonas aeruginosa to compounds in this antimicrobial class.

PMID- 8858454
TI  - Brodimoprim synergy against Enterococcus faecalis evaluated in vitro.
AB  - Combinations of either brodimoprim or trimethoprim plus either carbenicillin,
      gentamicin, ciprofloxacin or rifampicin showed synergy at sub-inhibitory
      concentrations against both Enterococcus faecalis NCTC 5957 and 775. Brodimoprim
      alone and in combination showed greater antibacterial activity against both
      strains of E. faecalis than trimethoprim. MBCs of brodimoprim and trimethoprim
      were 14.4 and 25.6 mg/L for E. faecalis NCTC 5957 and 7.2 and 12.8 mg/L for E.
      faecalis NCTC 775. Combinations of either brodimoprim or trimethoprim plus the
      other antibacterial agents, except gentamicin and dibromopropamidine isethionate,
      were bactericidal at achievable plasma concentrations. Viable count
      determinations of cultures of both test organisms in the presence of 3/4 of the
      MIC of each of the four antibiotics and the two antifolates alone and
      combinations of each antibiotic with either brodimoprim or trimethoprim indicated
      that only the combinations prevented recovery and regrowth of the cultures over
      24 h. The ATP released from cultures of both strains of E. faecalis treated with
      brodimoprim and trimethoprim at the same concentrations was approximately 1.5
      times greater with brodimoprim than with trimethoprim. Combinations of 3/4 of the
      MIC of each of the antibiotics in combination with 3/4 of the MIC of brodimoprim
      against cultures of both strains of E. faecalis resulted in greater release of
      ATP than occurred with equivalent trimethoprim combinations. It is postulated
      that the increased activities observed with the brodimoprim combinations resulted
      from an effect of brodimoprim on the bacterial cell permeability control. These
      results indicate that both brodimoprim and trimethoprim offer potential benefits
      for use with either carbenicillin, gentamicin, ciprofloxacin or rifampicin for
      the treatment of E. faecalis infections.

PMID- 8858455
TI  - Carbapenem resistance in Pseudomonas aeruginosa from cystic fibrosis patients.
AB  - The evolution of imipenem resistance was evaluated in Pseudomonas aeruginosa
      sequentially isolated from 42 patients with cystic fibrosis. Susceptibility was
      determined using a commercial microdilution system and imipenem resistance was
      confirmed by the agar dilution technique. Resistance to imipenem increased during
      the years from 1988 to 1992. A total of 12 patients (28.5%) carried resistant
      strains (11.6% of the total P. aeruginosa isolates) but only two of them were
      treated with the carbapenem. The other patient under imipenem treatment did not
      harbour resistant isolates. Sixty-four per cent of the imipenem resistant
      isolates were also meropenem resistant and showed low susceptibility to the other
      beta-lactams and tobramycin and amikacin. Twenty-one strains were selected for
      biochemical study. Imipenem susceptible strains showed normal OprD in two strains
      and diminished OprD in two more. Five strains with MIC of imipenem of 4-8 mg/L
      lacked OprD while another two had a band with decreased density. All strains with
      MIC higher than 8 completely lacked this band in western-blot analysis. Imipenem
      MICs of 0.5-2 mg/L only slightly increased to 1-4 mg/L when a pattern of beta
      lactamase derepression was observed. While those with imipenem MICs between 8-16
      mg/L increased the imipenem MIC to 16-64 mg/L in the population with a beta
      lactamase derepression phenotype.

PMID- 8858456
TI  - Evaluation of high-level carbapenem resistance in atypical Serratia marcescens by
      a comparison with its revertants.
AB  - A clinical isolate of Serratia marcescens (FHSM4055) was highly resistant to
      carbapenem (MIC of imipenem, 100 mg/L) and was atypical in that it was negative
      in the aesculin-hydrolysis test. This parent strain was compared with the
      revertants S1 and S5, which had lost resistance to imipenem alone and to imipenem
      and piperacillin respectively. The MICs of imipenem for the revertants were 16-
      to 32-fold lower than that for the parent strain. Only the crude extract of the
      parent strain had imipenem-hydrolyzing activity (0.27 unit/mg: panipenem-,
      meropenem- and biapenem-hydrolyzing activities were 53.4, 22.6 and 26.7% of the
      imipenem-hydrolyzing activity, respectively). From the isoelectric focusing
      profiles of beta-lactamases detected with nitrocefin, the parent strain produced
      beta-lactamases with pls of 9.2, 8.7 and 5.5, whereas the revertants did not
      produce the pI 8.7 beta-lactamase, which is a metalloenzyme. In the induction
      test, the pI 8.7 beta-lactamase was constitutive. These results indicated that
      the constitutive pI 8.7 beta-lactamase contributes to the carbapenem resistance
      of the parent strain. On the other hand, the MICs of imipenem for the revertants
      were 8- to 16-fold higher than that for the typical S. marcescens reference
      strain IFO3736, which was susceptible to various beta-lactam antibiotics other
      than first generation cephalosporins (according to the disk sensitivity test).
      This result revealed that the revertants were low-level resistant to carbapenem.
      The protein corresponding to the 42 kDa porin of strain IFO3736 (the major
      transport-channel) was absent on the outer membrane protein profiles of the
      parent strain and the revertants, and [3H]glucose uptake concomitantly decreased.
      Hence a combination of constitutive pI 8.7 metallo-beta-lactamase and decreased
      outer membrane permeability are major factors involved in the high-level
      carbapenem resistance of S. marcescens.

PMID- 8858458
TI  - Spectrophotometric determination of the morphogenetic transformation by
      synchronous Candida albicans: effects of antifungal agents.
AB  - A spectrophotometric method for studying the morphogenetic transformation by
      Candida albicans is described. Synchronous yeast-phase C. albicans cells
      incubated at 35 degrees C formed germ-tubes and resulted in an absorbance
      increase at 340 nm but not at 595 nm. Furthermore, measurements of germ tube
      length increases correlated strongly (r2 > 0.95) with increases in absorbance at
      340 nm during the morphogenetic transformation. Amphotericin B significantly
      affected the morphogenetic transformation, at the MIC and 1/10 MIC, whereby no
      increase in absorbance was observed at 340 nm. In contrast, identical
      measurements demonstrated that ketoconazole, at the MIC and 1/10 MIC, did not
      exhibit the same effects on the morphogenetic transformation by C. albicans
      cells.

PMID- 8858457
TI  - Comparative in-vitro activity of cefaclor against urinary tract isolates of
      Escherichia coli.
AB  - Insusceptibility levels of cefaclor and other commonly prescribed antibiotics
      were determined for 489 consecutive hospital and community-associated urinary
      tract isolates of Escherichia coli from the Nottingham area of the UK.
      Significant resistance (MIC of > or = 8 mg/L) to cefaclor was found to be
      uncommon in the UK, with insusceptibility percentages as low as 1.5% and 1.4%
      amongst hospital and community isolates, respectively. When compared with other
      antimicrobials used commonly for treating urinary tract infection, only
      ciprofloxacin showed greater activity, though cefaclor showed significantly
      greater in-vitro activity than cephalexin, ampicillin and trimethoprim. Only
      seven isolates were insusceptible to cefaclor at a concentration of 8 mg/L. Each
      of these isolates produced a beta-lactamase, but it is unlikely that beta
      lactamase production was the sole reason for insusceptibility since these
      isolates were also insusceptible to co-amoxiclav. Cefaclor compared extremely
      well with co-amoxiclav against ampicillin-insusceptible isolates, with none of
      the pharmacokinetic difficulties and considerations associated with the use of
      beta-lactam:beta-lactamase inhibitor combinations. Cefaclor appears to be a
      useful cost-effective alternative to current therapeutic options, particularly
      for long-term low-dose treatment of recurrent urinary tract infection in those
      geographical areas where the likelihood of resistance to other possible agents is
      becoming unacceptably high.

PMID- 8858459
TI  - Anti-toxoplasma effect of pyrimethamine, trimethoprim and sulphonamides alone and
      in combination: implications for therapy.
AB  - The aim of the present study was to determine the in-vitro susceptibility of
      Toxoplasma gondii to dihydrofolate reductase inhibitors and sulphonamides alone,
      and in combination. It was found that pyrimethamine had the most potent anti
      Toxoplasma activity, while sulphadiazine, sulphamethoxazole and sulphametrole
      were approximately equally effective, but only at a high concentration. The 50%
      inhibitory concentration of sulphamethoxazole was determined using different
      fixed concentrations of pyrimethamine or trimethoprim. It was found that a ten
      fold increment of the concentration of pyrimethamine, reduced the IC50 of
      sulphamethoxazole 1000 times. The influence of trimethoprim on the IC50 of
      sulphamethoxazole was less concentration dependent. Addition of dihydrofolate or
      tetrahydrofolate did not influence the IC50 of pyrimethamine. In conclusion, the
      present dose recommendations for sulphonamides, when combined with pyrimethamine,
      may be unnecessarily high. There may be a justification for dose reduction of
      sulphonamides in order to prevent side effects.

PMID- 8858460
TI  - Comparison of various macrolides on stimulation of human neutrophil degranulation
      in vitro.
AB  - Macrolide antibiotics are taken up and concentrated by host cells, particularly
      phagocytes, and are likely candidates to modify cell functions. In this study, we
      extended our previous work concerning the effect of three 14-membered-ring
      macrolides (dirithromycin, erythromycin and erythromycylamine) on human
      neutrophil exocytosis, and found that three other erythromycin A derivatives
      (roxithromycin, clarithromycin and the azalide, azithromycin) also triggered
      neutrophil degranulation in a time- and concentration-dependent manner. After 30
      min of incubation, the correlation coefficients for concentration-dependence for
      roxithromycin were 0.885, 0.739 and 0.750 (P < 0.005) and for clarithromycin were
      0.795, 0.599, 0.733 (P < 0.02), respectively, for lysozyme, beta-glucuronidase
      and lactoferrin release. Although the underlying mechanism was not elucidated,
      these and previous data suggest that intracellular accumulation is a
      prerequisite. Furthermore, comparison of the characteristics of macrolide-induced
      exocytosis with those of exocytosis triggered by the synthetic chemotactic
      stimulus FMLP suggested that different mechanisms are involved. In keeping with
      this possibility, we showed that combined treatment (macrolides plus FMLP)
      resulted in totally additive exocytosis of azurophilic but not specific granules.
      The clinical relevance of our data remains to be ascertained.

PMID- 8858461
TI  - Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei
      infected mice after rescue therapy with chloroquine or artemether.
AB  - Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a
      parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghei infected mice
      were treated with artemether, chloroquine or clindamycin in order to prevent the
      occurrence of cerebral malaria. Artemether and chloroquine were highly efficient.
      Functional tests revealed that zymosan stimulated spleen cells from untreated
      mice with cerebral malaria showed a slight decrease in their capacity to produce
      reactive oxygen intermediates (ROI) when compared with naive mice. After
      artemether or chloroquine treatment, the ROI production was significantly
      enhanced. The interferon-gamma induced production of reactive nitrogen
      intermediates (RNI) was slightly elevated in mice with cerebral malaria, but
      markedly elevated in artemether or chloroquine treated mice when compared with
      naive mice. Moreover, high levels of inducible nitric oxide synthase gene
      expression could be detected by in-situ hybridization in spleen sections of mice
      which had been treated with artemether or chloroquine. These findings suggest
      that increased production of ROI and RNI after chemotherapy may play a protective
      role for the host during malaria.

PMID- 8858462
TI  - Pharmacokinetics of intravenous ciprofloxacin in normal and renally impaired
      subjects.
AB  - The pharmacokinetics of intravenous ciprofloxacin and its metabolites were
      characterized in 42 subjects with various degrees of renal function (group 1,
      Clcr (mL/min/1.73 m2) > 90, n = 10; group 2, Clcr 61-90, n = 11; group 3, Clcr 31
      60, n = 11; group 4, Clcr < or = 30, n = 10). The dosage regimens were-groups 1
      and 2: 400 mg i.v. at 8 hourly intervals; group 3: 400 mg i.v. at 12 hourly
      intervals and group 4: 300 mg i.v. at 12 hourly intervals. Subjects received a
      single dose on days 1 and 5 and multiple doses on days 2-4. Multiple plasma and
      urine samples were collected on days 1 and 5 for the analysis of ciprofloxacin
      and its metabolites (M1, M2 and M3). Plasma concentrations (Cmax and AUC) of
      ciprofloxacin and its M1 and M2 metabolites were significantly increased in
      subjects with reduced Clcr values (Clcr < 60 mL/min/1.73 m2) compared with normal
      subjects (Clcr > 90 mL/min/1.73 m2). A positive correlation was observed between
      ciprofloxacin clearance (Cl) and Clcr with a slope of 0.29 (r2 = 0.78) and
      between renal clearance (Clr) and Clcr with a slope of 0.19 (r2 = 0.84). For
      patients with severe infections a dosage regimen of 400 mg iv 8 hourly is
      appropriate in patients with Clcr > 60 mL/min/1.73 m2. In patients with Clcr
      values of 31-60 mL/min/1.73 m2 a dosage regimen of 400 mg 12 hourly provides
      similar plasma concentrations to those observed for subjects with Clcr 61-90
      mL/min/1.73 m2 receiving 400 mg 8 hourly. Based on modeling of the plasma
      concentrations in subjects with Clcr < or = 30 ml/min/1.73 m2, a dosage regimen
      of 400 mg every 24 h will provide plasma concentrations similar to those observed
      in subjects with Clcr between 61-90 mL/min/1.73 m2 given 400 mg every 8 h.

PMID- 8858463
TI  - Amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis
      in AIDS patients.
AB  - We determined the safety and efficacy of deoxycholate-amphotericin B (d-AmB)
      mixed with Intralipid (IL) as the initial treatment of AIDS-associated
      cryptococcal meningitis in a phase II, multicentre, non-comparative open study,
      assessing two dosages of ILd-AmB: 1 mg/kg (group A, n = 9) and 1.5 mg/kg (group
      B, n = 6). Patients were treated daily for 2 weeks, then three times weekly for 4
      weeks. The ILd-AmB dosage was decreased due to toxicity in three patients in each
      group. Serum creatinine increased significantly on day 14 in group A and on day 7
      in group B. Nephrotoxicity, (serum creatinine level > 165 mumol/L) was noted in
      two and five patients in groups A and B, respectively. Nine adverse
      haematological events were noted (seven cases of anaemia requiring transfusion,
      and two cases of neutropenia < 750/mm). Two patients had an increase in serum
      alkaline phosphatase. In each cohort, 15% of the infusions were associated with
      fever and/or chills. Successful outcome was obtained in half of the patients. We
      conclude that, in AIDS patients with cryptococcosis, tolerance to ILd-AmB was
      acceptable when the daily dosage did not exceed 1 mg/kg, but the higher 1.5 mg/kg
      daily dosage was associated with an unacceptable rate of nephrotoxicity. Neither
      of these relatively high daily dosages of ILd-AmB achieved an improved rate of
      successful outcomes compared with lower daily dosages of conventional d-AmB in
      glucose.

PMID- 8858464
TI  - Survey of prevalence of extended spectrum beta-lactamases among
      enterobacteriaceae.
AB  - During the first six months of 1990 and 1994 respectively, 3179 and 2721 non
      repetitive strains of Enterobacteriaceae were isolated at the teaching hospital
      of Clermont-Ferrand. Extended-spectrum beta-lactamases were found in 147
      isolates, mainly in Klebsiella pneumoniae (n = 73), Enterobacter aerogenes (n =
      37) and Proteus mirabilis (n = 15). TEM-3/CTX-1, SHV-4/CAZ-5 and TEM-24/CAZ-6
      were the prevalent enzymes. However, the most frequently involved enzyme in 1990
      was TEM-3 (48.6%) whereas in 1994 it was SHV-4 (56.0%). Two salient features
      emerged from this study: the high frequency of TEM-3 production in P. mirabilis
      and the production of SHV-4 enzyme, heretofore observed solely in K. pneumoniae,
      in two other species, E. aerogenes and Escherichia coli.

PMID- 8858465
TI  - A mechanism of rifamycin inhibition and resistance in Pseudomonas aeruginosa.
AB  - We sought to study the nature of rifampicin resistance in Pseudomonas aeruginosa.
      We hypothesized that the rifamycin regions of RNA polymerase are conserved in P.
      aeruginosa and that rifampicin resistance is mediated by a mutation in the rpoB
      gene encoding the beta subunit of RNA polymerase. Transcription assays showed
      that 50 nM of rifampicin inhibited transcription > 99% in a clinical isolate (MIC
      = 32 mg/L) and only < 40% in the rifampicin resistant mutant (MIC = 1000 mg/L).
      DNA sequencing revealed that the rifampicin regions are conserved in P.
      aeruginosa and the rifampicin regions of the rifampicin-resistant strain
      contained a mutation. Sodium hexametaphosphate lowered rifamycin MIC in a
      rifamycin-resistant mutant four-fold and in the clinical isolate 32-fold,
      suggesting that P. aeruginosa has a natural membrane barrier to rifamycins.

PMID- 8858466
TI  - Effect of ciprofloxacin on ciliary motility of rabbit airway epithelium.
AB  - To determine the effect of the new quinolone ciprofloxacin on airway ciliary
      motility, we studied ciliary beat frequency (CBF) of rabbit tracheal epithelium
      using an in-vitro microphoto-oscillation method. Incubation of the cells with
      ciprofloxacin increased CBF in a concentration-dependent manner, the maximal
      increase from the baseline value and the EC50 being 17.1 +/- 2.0% (P < 0.01) and
      10(-7.25) M, respectively. This ciliary stimulatory effect was not affected by
      propranolol or indomethacin but was nullified by verapamil. These results suggest
      that ciprofloxacin probably increases airway epithelial ciliary motility by
      facilitating Ca2+ influx through a voltage-dependent channel.

PMID- 8858467
TI  - Drug delivery system: targeting of pentamidines to specific sites using sugar
      grafted liposomes.
AB  - Different sugar-grafted liposomes were prepared and tested against experimental
      leishmaniasis in vivo using the classical drug pentamidine isethionate and its
      methoxy derivative. Both the drugs, when encapsulated in sugar-grafted liposomes
      were found to be more potent in comparison to normal liposome-encapsulated drug
      or to the free drug. Moreover, the mannose-grafted liposomes were adjudged to be
      the best in lowering of spleen parasite load in comparison with those bearing
      glucose or galactose. When encapsulated in mannose-grafted liposomes the
      therapeutic efficacy of pentamidine isethionate was found to be better than that
      of its methoxy derivative, although the latter seemed to be less toxic than the
      pentamidine isethionate itself.

PMID- 8858468
TI  - Acidic pH and beta-lactam activity.

PMID- 8858469
TI  - Are ciprofloxacin susceptibility tests relevant for Streptococcus pneumoniae?

PMID- 8858470
TI  - In-vitro activity of antiviral agents used in AIDS against Salmonella typhi and
      non-typhoid salmonella.

PMID- 8858471
TI  - Efficacy and tolerance of amphotericin B in a lipid emulsion in the treatment of
      visceral leishmaniasis in AIDS patients.

PMID- 8858472
TI  - A multicentre collaborative study of the antimicrobial susceptibility of
      community-acquired, lower respiratory tract pathogens 1992-1993: the Alexander
      Project.
AB  - The Alexander Project is a unique, international, collaborative antimicrobial
      susceptibility surveillance study of bacterial pathogens causing community
      acquired lower respiratory tract infection. Fifteen centres, ten in the European
      Union (EU) and five in the USA, each submitted up to 400 isolated per year for 2
      years (1992 and 1993) to a central laboratory for re-identification and
      determination of MICs of 15 antimicrobials using the Sensititre microbroth
      incorporation technique. Of the total of 6385 isolates collected, Haemophilus
      influenzae (2718), Streptococcus pneumoniae (1856) and Moraxella catarrhalis
      (818) were the most frequently identified pathogens. Staphylococcus aureus (690).
      Haemophilus parainfluenzae (183) and Klebsiella pneumoniae (120) were identified
      less commonly. High-level penicillin resistance in S. pneumoniae (MIC > or = 2
      mg/L) was found in 222 isolates, an overall prevalence of 12% which varied from <
      1% in Germany, Italy, UK and two of the five USA centres, to 3.8-40.4% in the
      remainder, with the highest prevalence found in France and Spain. Intermediate
      penicillin resistance (MIC 0.12-1 mg/L) was identified in 228 isolates of S.
      pneumoniae, an overall prevalence of 12.3%, with individual centre prevalence
      varying widely (EU, 0-52.3%; USA, 0-20.9%) and not always following that of high
      level resistance. Resistance to other, unrelated, antimicrobials, except notably
      the fluoroquinolones, was strongly associated with beta-lactam resistance. beta
      lactamase production was detected in 492 isolates of H. influenzae, an overall
      prevalence of 18.1%. Rates of detection varied widely between centres from 1.4%
      in Weingarten, Germany in 1993 to 38.5% in Barcelona, Spain in 1992. In general,
      the prevalence of beta-lactamase production was higher and less variable in USA
      centres than in those of the EU. beta-Lactamase was detected consistently in the
      majority of isolates of M. catarrhalis with an overall prevalence of 81.7%.
      Virtually no other resistance phenotype was recognised in this species. Of the
      690 collected, most isolates of S. aureus produced beta-lactamase with rates of
      detection varying from 52.2%-89.1%. Isolates from two centres, Genoa, Italy in
      1992 and Paris, France in 1993, were associated with a high prevalence of
      methicillin-resistance (34.8% and 43.8%, respectively). Combined isolates of H.
      parainfluenzae and K. pneumoniae accounted for only 4.7% of the total collection.
      Although the current data are insufficient to allow analysis of trends in
      resistance, the study participants have continued to collect further isolates in
      1994 and 1995 which will be reported in the future.

PMID- 8858473
TI  - Antimicrobial resistance among lower respiratory tract isolates of Haemophilus
      influenzae: results of a 1992-93 western Europe and USA collaborative
      surveillance study. The Alexander Project Collaborative Group.
AB  - During 1992 and 1993, 2718 respiratory tract isolates of Haemophilus influenzae
      were obtained from two study centres in each of five West European countries and
      five study centres in the USA. beta-Lactamase production was assessed and MICs of
      14 antimicrobial agents determined in a single co-ordinating laboratory using a
      broth microdilution method in Mueller-Hinton-lysed horse blood medium. The
      prevalence of strains producing beta-lactamase varied between 0 and 37.9%. In
      general, the highest prevalence was in study centres from Spain and the USA with
      slightly lower rates observed in France and the UK. Only a single confirmed beta
      lactamase-negative, ampicillin resistant strain was recovered during the entire
      study. Erythromycin resistance, defined as an MIC of > or = 4.0 mg/L, was noted
      in 57.5% of isolates. Among the other antimicrobials tested, resistance rates >
      or = 1.0% were observed only with cefaclor (3.7%), chloramphenicol (1.4%) and co
      trimoxazole (2.5%). In no case, was the prevalence of resistance or beta
      lactamase production significantly greater in 1993 than in 1992.

PMID- 8858474
TI  - Antimicrobial resistance among lower respiratory tract isolates of Streptococcus
      pneumoniae: results of a 1992-93 western Europe and USA collaborative
      surveillance study. The Alexander Project Collaborative Group.
AB  - One thousand, eight hundred and fifty-six Streptococcus pneumoniae strains,
      collected in 1992 and 1993 from 15 centres in Western Europe and USA were tested
      for susceptibility to 16 antibiotics. The overall resistance to penicillin was
      23% (range 6-54%), with the highest prevalences in Madrid, Barcelona, Toulouse
      and Cleveland. Seven centres reported low-level penicillin resistance only.
      Amoxycillin was more active than ceftriaxone against strains with intermediate
      resistance to penicillin, and at least four-fold more active than cefuroxime;
      cefaclor and cefixime had poor activity. Against penicillin-resistant strains,
      ceftriaxone was slightly more active than amoxycillin, cefuroxime exhibited
      borderline activity and cefixime and cefaclor were inactive. Ten strains fully
      susceptible to penicillin had MICs of ceftriaxone > or = 0.1 mg/L; this may
      represent a first step towards the development of cephalosporin resistance. With
      the exception of fluoroquinolones, resistance to non-beta-lactam antibiotics
      (chloramphenicol, doxycycline, co-trimoxazole, erythromycin, clarithromycin and
      azithromycin) was considerably higher in penicillin-resistant strains compared
      with penicillin-susceptible isolates. Erythromycin-resistant isolates were also
      resistant to the other macrolides tested.

PMID- 8858475
TI  - Antibiotic susceptibility patterns of community-acquired respiratory isolates of
      Moraxella catarrhalis in western Europe and in the USA. The Alexander Project
      Collaborative Group.
AB  - Eight hundred and eighteen Moraxella catarrhalis strains, isolated in 1992 and
      1993 at 15 centres in Western Europe and the USA were tested for beta-lactamase
      production and resistance to 15 antibiotics. The proportion of beta-lactamase
      producing strains in Europe rose significantly from 70% in 1992 to 82% in 1993,
      whilst in the USA the increase (85-92%) was not significant. Penicillin and
      amoxycillin resistance was more prevalent in the USA than in Europe. All
      penicillin-resistant strains isolated in the USA exhibited beta-lactamase
      activity, whilst 8% of beta-lactamase-negative strains isolated in Europe were
      also penicillin resistant. All but three isolates were sensitive to cefaclor,
      cefuroxime, cefixime and ceftriaxone, all but one were sensitive to ofloxacin and
      all were sensitive to ciprofloxacin and amoxycillin cluvulanate. Resistance to
      erythromycin was not encountered, although 19 strains had MICs > or = 0.5 mg/L.
      Of these, 15 came from European centres. Almost all strains were highly
      susceptible to clarithromycin, azithromycin, doxycycline and co-trimoxazole.

PMID- 8858476
TI  - Susceptibility of respiratory strains of Staphylococcus aureus to fifteen
      antibiotics: results of a collaborative surveillance study (1992-1993). The
      Alexander Project Collaborative Group.
AB  - As part of the Alexander Project during 1992 and 1993, 690 Staphylococcus aureus
      strains isolated from community-acquired lower respiratory tract infections by
      clinical microbiology centres located in Europe and the USA were analysed by a co
      ordinating laboratory that determined minimal inhibitory concentrations of 15
      antimicrobial agents using a standardised microdilution technique. The prevalence
      of penicillin-susceptible microorganisms in this collection of pathogens was
      significantly higher in Europe (21.2%) than it was in the USA (12.1%). Most
      isolates (72.5%), however, were strains that had acquired the ability to
      synthesise a beta-lactamase but which were sensitive to methicillin. The
      incidence of methicillin-resistance (9.1% overall) was highly variable depending
      on geographic location and year of isolation. Analysis of MIC50, MIC90, MIC range
      and modal MIC of the 15 antibiotics assayed disclosed no major differences
      between the data sets obtained during the 2-year survey. Except for methicillin
      resistant S. aureus, the activity of all the beta-lactams tested, with the
      exclusion of penicillin, amoxycillin and cefixime (that were completely
      inactive), was satisfactory. The effect of beta-lactamase synthesis was inhibited
      by the combination of amoxycillin with clavulanate, and by cefuroxime and
      ceftriaxone. Cefaclor was slightly less effective. Erythromycin, clarithromycin
      and azithromycin showed identical cross-resistance rates (around 10%). Resistance
      to the macrolides was more frequent in the USA than in Europe and was the sole
      trait found to increase during the survey. Doxycycline, chloramphenicol, co
      trimoxazole and the two fluoroquinolones tested (ofloxacin and ciprofloxacin)
      were remarkably effective (resistance lower than 1%). Only doxycycline and, to a
      lesser extent, co-trimoxazole were partially active against methicillin-resistant
      strains.

PMID- 8858477
TI  - Antibiotic susceptibility patterns of respiratory isolates of Klebsiella
      pneumoniae in Europe and the USA in 1992 and 1993. The Alexander Project
      Collaborative Group.
AB  - The overall antibiotic susceptibility of Klebsiella pneumoniae isolates collected
      in 1992 (n = 35) and 1993 (n = 85) was highly variable ranging from 0.8% for
      amoxycillin to 95.8% for ceftriaxone. On a weight for weight basis, the activity
      of the compounds decreased in the following sequence: ceftriaxone, cefixime, co
      trimoxazole, ciprofloxacin, ofloxacin, cefaclor, amoxycillin/clavulanate,
      doxycycline, cefuroxime, chloramphenicol, amoxycillin. A small percentage of
      resistant strains was found for each of the compounds (between 0.8% for
      ceftriaxone and 12.5% for chloramphenicol) with the exception of amoxycillin
      which was almost uniformly resistant. There was a trend for the percentage of
      resistant strains to increase between the two study years for all compounds
      except for chloramphenicol. Resistance to beta-lactams in France and the USA is
      likely to have been due to strains producing extended spectrum beta-lactamases.

PMID- 8858478
TI  - Trends in antibiotic resistance of respiratory pathogens: an analysis and
      commentary on a collaborative surveillance study.
AB  - The evolution of antibiotic resistance was studied among common respiratory tract
      pathogens in five countries of the European Union and in the USA during 1992
      1993. The data obtained from a collaborative surveillance study were submitted to
      population analysis, to detect possible shifts in antibiotic susceptibility and,
      therefore, associated mechanisms of resistance. Among the emerging haemophilus
      influenzae phenotypes were isolates that did not correspond to the beta-lactamase
      negative, amino-penicillin resistant (BLNAR) phenotype, but were beta-lactamase
      producers showing low level ceftriaxone resistance (early extended spectrum beta
      lactamases?) amoxycillin susceptible strains with low level ceftriaxone
      resistance (PBP modification?) and isolates with high-level fluoroquinolone
      resistance. Moraxella catarrhalis resistance to ceftriaxone erythromycin or
      fluoroquinolones was noted. The quantitative evolution of antibiotic resistance
      may reach saturation in some countries with a very high proportion of resistant
      strains, for example, Spain and France. Qualitatively, resistant strains may be
      selected that have broader or more effective mechanisms of resistance,
      particularly under the recently introduced pressure of more active antibiotics of
      the same family. In countries with modest levels of antibiotic resistance (UK,
      Germany, Italy), attention should be paid to the misuse of antibiotics with a
      propensity to select low-level resistant strains. In this respect, the relative
      prescribing of aminopenicillins and oral cephalosporins in the UK (a high ratio
      and low prevalence of Streptococcus pneumoniae) and resistance to penicillin in
      the USA (a low ratio and high prevalence of resistance) is of potential
      importance.

PMID- 8858479
TI  - The clinical relevance of in-vitro resistance to penicillin, ampicillin,
      amoxycillin and alternative agents, for the treatment of community-acquired
      pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae and
      Moraxella catarrhalis.
AB  - The documentation of antimicrobial resistance in respiratory pathogens, contained
      within the Alexander Project, does not necessarily translate into clinical
      resistance in the treatment of primary community-acquired pneumonia. There is, in
      particular, little evidence that penicillin resistance in pneumococci is
      clinically relevant for the treatment of pneumonia, and there is further evidence
      that the production of beta-lactamase by Haemophilus influenzae may not always be
      clinically relevant within this setting. beta-Lactamase producing H. influenzae
      and Moraxella catarrhalis should probably be treated with alternative agents when
      they cause exacerbations of chronic bronchitis. More studies are required to
      define the clinical breakpoints of macrolide and co-trimoxazole resistance in the
      treatment of pneumonia.

PMID- 8858481
TI  - The Alexander Project: using in-vitro susceptibility data for choosing empirical
      therapy in LRTI.
AB  - An international collaborative survey of susceptibility in community-acquired
      lower respiratory tract infection pathogens collected > 6000 strains from six
      countries during 1992 and 1993. The four major pathogens were Streptococcus
      pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus
      aureus. MICs of 15 antibiotics were determined and sensitivity interpretations
      applied using breakpoints based on those of the NCCLS. This analysis highlighted
      some anomalies, notably for beta-lactams against S. pneumoniae and macrolides
      against H. influenzae, where apparent sensitivity proportions did not accord with
      the distribution of MICs. Further analyses were undertaken in order to rank the
      antibiotics in order of potential usefulness for empirical treatment of LRTI:
      these included in-vitro potency (mode MIC and MIC90) and a pharmacodynamic
      comparison, using the ratio Cmax (free drug): MIC90. According to study
      breakpoints, the most active agents overall were, for S. pneumoniae, cefuroxime,
      clarithromycin, ofloxacin and chloramphenicol; for H. influenzae, azithromycin,
      amoxycillin/ clavulanate, cefixime, ceftriaxone, quinolones and doxycycline.
      However, other analyses suggested that the most active agents overall were, for
      S. pneumoniae, amoxycillin (+/- clavulanate) and ceftriaxone, and, for H.
      influenzae, quinolones, ceftriaxone, cefixime and amoxycillin/clavulanate.
      Overall, the antimicrobial agents with the greatest potential usefulness for
      empirical treatment were amoxycillin/ clavulanate, ceftriaxone, cefuroxime,
      ofloxacin and co-trimoxazole. The choice of empirical therapy depends upon local
      epidemiology and clinician choice, but the Project data may be of value in the
      decision-making process.

PMID- 8858480
TI  - Relevance of the Alexander Project: pharmacodynamic considerations.
AB  - Application of pharmacodynamic principles for interpretation of data generated by
      the Alexander Project is possible for beta-lactam, quinolone and macrolide
      antibiotics. For beta-lactams, the time that serum concentrations remain above
      the MIC of the pathogen (T > MIC) is the parameter most closely linked with
      outcome. It has been shown that T > MIC need be only 50-60% of a dose interval.
      Since the MIC has the greatest influence on this parameter, a conservative
      estimate of activity would use the MIC90. The only beta-lactam antibiotics in the
      Alexander Project for which T > MIC90 for the four major pathogens (Streptococcus
      pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus
      aureus) exceeded 50% of the dose interval were amoxycillin/clavulanate (500/125
      mg) and ceftriaxone. For macrolides, T > MIC is relevant for erythromycin and
      clarithromycin, but not azithromycin, for which AUC is the parameter most closely
      linked to outcome. Erythromycin, clarithromycin and azithromycin showed efficacy
      against M. catarrhalis only at MIC90. Quinolones (ciprofloxacin and ofloxacin),
      for which AUC is also the relevant pharmacodynamic parameter, had the greatest
      activity against H. influenzae and M. catarrhalis at MIC90, but were less
      effective against S. pneumoniae and S. aureus. Susceptibility data such as those
      provided by the Alexander Project can aid clinicians in choosing appropriate
      treatment for LRTI based on pharmacodynamic principles.

PMID- 8858482
TI  - Glucoamylase absorption and desorption process.
AB  - This paper reports the study of glucoamylase absorption and desorption processes
      on spherical particles constituting acrylic supports. The kinetic (reaction
      order, half-life of the reaction, reaction rate constant), and thermodynamic
      parameters (activation energy, pre-exponential factor) of the glucoamylase
      immobilization reaction dynamics inside the acrylic supports have been studied.
      Hindrance of the penetrants (protein molecules), which defeats the polymer's
      cohesive forces and passes through the diffusional barriers towards the sites
      available to receive it, denotes the influence of the diffusion phenomena, and
      might be expressed by the values of the effective diffusion coefficient and of
      the energetic parameters, as well. The desorption dynamics of glucoamylase in
      specific buffer concentration gradients and temperature are dependent on the
      eluent volume and on the protein eluate.

PMID- 8858483
TI  - Properties controlling the diffusion and release of water-soluble solutes from
      poly(ethylene oxide) hydrogels: 3. Device geometry.
AB  - The diffusive release from hydrogels can be determined by both composition and
      geometry. This paper presents a theoretical and experimental comparison of the
      release characteristics of proxyphylline in water-swollen slabs, spheres, and
      cylinders of a urethane cross-linked poly(ethylene oxide). Contrary to general
      conventional wisdom it was found that practically cylinders and spheres, which
      have considerable potential advantages for oral delivery, can provide good
      'anomalous' rates for which the 'exponent of release' into water from the dry
      xerogels is c. 0.8 compared with 1.0 for zero order. An exponent of 0.94 was
      found for release into water from 'larger' xerogel flat slabs thus confirming
      that these configurations can provide essentially constant delivery formulations
      from which the active agent cannot be 'dumped'. For up to 40% total drug release,
      the theoretical release profiles were essentially of identical form for all three
      geometries in the swollen state and, as expected in theory and practice, showed
      an exponent for release of close to 0.5. However, the experimental release of
      proxyphylline was found to be more sustained from swollen spheres of these
      polymers than theory would predict. The half life times for release were further
      extended by approximately two and a half times for the initially dry devices
      compared with the initially swollen ones.

PMID- 8858484
TI  - Properties controlling the diffusion and release of water-soluble solutes from
      poly(ethylene oxide) hydrogels. 4. Extended constant rate release from partly
      coated spheres.
AB  - Spheres of poly(ethylene oxide) xerogel from 4-17 mm diameter were impregnated
      with the drug, proxyphylline, or the herbicide, 2,4-DNa and then partly coated
      with a water-impermeable elastomer. When placed in water the active additive was
      released over periods ranging from hours to weeks at a nearly constant rate. The
      effect of the hydrogel sphere dimensions and the window size through the
      elastomer, on water uptake and consequent release of the active agent were
      examined. These devices superficially possess a configuration similar to some
      commercial osmotic devices though the active-agent release from the devices of
      this paper is, in fact, diffusive and not osmotically driven. They appear to
      provide a very versatile and simple design allowing relatively constant release
      of the active agent over periods of hours to months merely by changing the device
      geometry.

PMID- 8858485
TI  - Responses of oral epithelial cells to dental resin components.
AB  - The light-polymerized resins used in dentistry and their various constituents
      have been shown to produce significant levels of cytotoxicity, depending upon the
      material and the cell type exposed to it. These responses include altered cell
      growth and macromolecule synthesis. The current study examined the effects of
      several resin components on growth and lipid metabolism of oral epithelial cells.
      Resin discs were fabricated from triethyleneglycol dimethacrylate (TEGDMA) as
      received from the manufacturer and after removal of the stabilizer methyl ether
      hydroquinone (MEHQ). Some discs also contained the initiators benzoyl peroxide
      (BPO) and camphoroquinone (CQ), and/or an activator, dimethylaminoethyl
      methacrylate (DMAEMA). After polymerization, the ability of components to elute
      from the discs and alter cell growth and lipid synthesis were assayed by a
      colorimetric method and thin layer chromatography respectively. Purified TEGDMA
      had little effect on the cells' growth or lipid metabolism, while TEGDMA
      containing MEHQ did inhibit growth as well as total polar lipid synthesis.
      Eluates from discs containing DMAEMA inhibited cell growth as well as decreasing
      polar lipid formation. However, this same material produced increased synthesis
      of diglycerides and cholesterol esters. Eluates from BPO-containing discs, as
      well as those with CQ, with or without DMAEMA resulted in increased levels of
      diglycerides. These results demonstrate that even after polymerization,
      components used in dental resins may elute into the immediate environment and
      alter various cell metabolic processes.

PMID- 8858486
TI  - Platelet interactions with plasma-polymerized ethylene oxide and N-vinyl-2
      pyrrolidone films and linear poly(ethylene oxide) layer.
AB  - Dimethyldichlorosilane (DDS)-treated glass (DDS-glass) was modified with either
      poly(ethylene oxide) (PEO) films or poly(N-vinyl-2-pyrrolidone) (PNVP) films by
      plasma polymerization. The thickness of the plasma polymerized films was varied
      between 40 and 700 nm. The results showed that the hydrophilic plasma polymerized
      PEO and PNVP films on DDS-glass did not prevent platelet adhesion and activation.
      The film thickness had only marginal influence on the prevention of platelet
      activation. In contrast, platelet adhesion was prevented on DDS-glass absorbed
      with a PEO-containing block copolymer (Pluronic F-108 surfactant) even at a
      calculated thickness of the PEO layer of less than 40 nm. This study shows that
      surface hydrophilization is not sufficient for prevention of platelet adhesion
      and activation. The contrasting results in platelet adhesion between cross-linked
      plasma polymers and linear PEO-containing block copolymers may be explained
      qualitatively by a steric repulsion mechanism that is achieved by the
      conformational freedom of the linear PEO chains interacting with water.

PMID- 8858487
TI  - The interactions between antithrombin III, thrombin and surface immobilized
      heparin.
AB  - The interactions between antithrombin III (ATIII), thrombin, and surface
      immobilized heparin were investigated. Carboxylated polystyrene modified with
      covalently immobilized albumin-heparin conjugate contain sites which can bind
      ATIII from buffer and plasma solutions. Approximately 65% of the ATIII molecules
      present at the heparinized surface either adsorbed from a buffer or plasma
      solution, exchanged with ATIII in buffer solution. The exchange between surface
      bound ATIII and ATIII in solution was repeated several times on the same
      heparinized surface. The number of binding sites that could bind and release
      ATIII was much higher when the heparinized surface was exposed to an ATIII
      containing buffer solution than to a plasma solution. The reduction in binding
      sites available for ATIII using plasma solutions as compared to buffer solutions
      could be explained by the competition of other plasma proteins with ATIII for the
      heparinized surface. It was observed that heparin binding proteins were able to
      compete with ATIII for binding to the immobilized heparin. Furthermore adsorption
      of proteins on the heparinized surface significantly reduced the availability of
      binding sites for ATIII. Exposure of thrombin to the heparinized surface resulted
      in thrombin activity at the surface. The thrombin activity on the heparinized
      surfaces was lower on surfaces with a higher ATIII concentration. The activity of
      surface bound thrombin was not affected by the presence of other plasma proteins.
      Enzymatically active thrombin molecules present at the heparinized surface were
      completely inactivated when the surface was exposed to a solution containing
      ATIII. The inactivation rate of surface bound thrombin by ATIII was higher than
      the rate of the uncatalyzed inactivation of thrombin in solution. Part of the
      Thrombin-Antithrombin III (TAT) complexes (10-20%) that were formed upon
      inactivation of thrombin remained bound to the heparinized surface. In general it
      was concluded that only the surface immobilized heparin molecules that can bind
      ATIII in a reversible way determine the anticoagulant properties of the surface.
      The mechanism of inactivation of a protease on a heparinized surface depends
      either on the catalytic effect of heparin on the inactivation rate of proteases
      by ATIII or on an increased uncatalytic inactivation due to increased
      concentrations of ATIII near the surface as compared to the concentration of
      ATIII in the bulk phase.

PMID- 8858488
TI  - Cytotoxicity tests for antimicrobial agents using cultured skin substitutes fixed
      at interface of air and culture medium.
AB  - The present study is focused on a new cytotoxicity test using cultured dermal and
      epidermal sheets, which are fixed at the air and medium interface as a wound
      surface model. The cultured dermal sheet is composed of human fibroblasts and a
      collagen matrix, and the cultured epidermal sheet is composed of human
      keratinocytes and a collagen matrix. Each cultured sheet was fixed at the air and
      medium interface, over which a piece of test specimen was placed. The in vitro
      system created, provides a mimetic wound surface since during wound repair,
      fibroblasts are embedded in an extracellular matrix, while keratinocytes migrate
      and proliferate on provisional granulation tissue. The results thus obtained in
      this cytotoxicity test are useful for determining the efficacious amount of
      antimicrobial agent used in clinical cases.

PMID- 8858489
TI  - Polymeric membranes for hybrid liver support devices: the effect of membrane
      surface wettability on hepatocyte viability and functions.
AB  - Extracorporeal therapies based on membrane hybrid liver support devices using
      primary hepatocytes are an interesting approach to the treatment of acute hepatic
      failure. In such devices, semipermeable polymeric membranes are effectively used
      as immunoselective barriers between a patient's blood and the xenocytes in order
      to prevent the immune rejection of the graft. The membranes may act also as the
      substratum for cell adhesion, thus favouring the viability and functions of
      anchorage-dependent cells such as the hepatocytes. Membrane cytocompatibility is
      expected to depend on the surface properties of the polymer, such as its
      morphology and its physico-chemical properties. In this paper, we report our
      investigation on the effect of the surface wettability of membranes on hepatocyte
      viability and functions. Polypropylene microporous membranes were modified to
      increase their surface wettability and were used as substrata for rat hepatocyte
      adhesion culture. Isolated hepatocytes were also cultured on collagen as a
      reference substratum. Hepatocyte viability generally improved as the cells were
      cultured on more wettable membranes. In agreement with the viability data, the
      increasing wettability of the membrane surface also improved some metabolic
      functions.

PMID- 8858490
TI  - Home assessment of sleep disorders by portable monitoring.
AB  - Ambulatory home monitoring has been employed for a number of applications.
      Portable sleep/wake recorders are useful for assessment of the hypersomnias,
      circadian sleep/wake disorders, parasomnias, and periodic movements in sleep.
      Wrist actigraphy can usefully approximate sleep versus wake state during 24 h and
      has been used for monitoring insomnia, circadian sleep/wake disturbances, and
      periodic limb movement disorder. Home monitoring of cardiopulmonary parameters
      can be employed for detection and follow-up of sleep-disordered breathing (sleep
      apnea, upper airway resistance syndrome). The techniques available for portable
      monitoring, although valuable, do not replace traditional in-laboratory
      polysomnography for full assessment of a sleep disorder.

PMID- 8858491
TI  - The future of computer-assisted investigation of the polysomnogram: sleep
      microstructure.
AB  - Previous attempts at automated analysis of sleep were mainly directed towards
      imitating the Rechtschaffen and Kales rules (RKR) in order to save scoring time
      and further objectify the procedure. RKR, however, do not take into consideration
      the sleep microstructure of REM, stage 2, and SWS. While the microstructure of
      stage 2 has been analyzed in the past decade, the microstructure of REM and SWS
      are virtually unknown. In stage 2 the amount and distribution of spindles, K
      complexes, and arousal reactions have been studied. At least two types of
      spindles (12/s and 14/s) with different dynamics and locations have been
      identified. Two different shapes for K complexes have been described: one related
      to external sensory stimuli with similarities to evoked potentials and another
      one more related to sinusoidal slow wave activity seen in SWS. These two
      different K complex shapes have different distributions and, obviously, different
      functions. The authors also suggest that one should differentiate between arousal
      reactions and true arousals. Recent investigations suggest two types of delta
      waves in SWS. The more sinusoidal 1-3/s delta waves with a frontal maximum are
      already seen with lower amplitude in late stage 2 and increase their amplitude
      and incidence towards stage 3 and Stage 4. The other delta-wave type is slower (<
      1/s), polymorphic, and has varying amounts of theta and higher frequency waves
      superimposed. During REM sleep it seems to be important to separate phases with
      rapid eye movements from those with none (REM sine REM), and count the amount and
      distribution of sawtooth activity. Background activity during REM and REM sine
      REM, as well as intra- and interhemispheric coherence should be analyzed
      separately. Only if the microstructure of the sleep EEG can be analyzed
      automatically using newer techniques such as transformation into wavelets and
      pattern classification with neuronal networks, and only if we learn more about
      the importance of microstructure elements, can automated sleep analysis go beyond
      the limited information obtained from scoring according to RKR.

PMID- 8858492
TI  - Past and future of computer-assisted sleep analysis and drowsiness assessment.
AB  - The development of computerized sleep analysis has been very much technology
      driven by both mathematical tools and available hardware but, additionally and
      unfortunately, by the almost-30-year-old standard used for manual sleep stage
      scoring of paper recordings. There are no technical restrictions in terms of
      computing power, storage space, and costs anymore. However, the standards of
      visual sleep stage scoring have proven insufficient and ambiguous, and their
      utilization evidently provides misleading and erroneous information. The low
      temporal resolution provided by the one-page epoch, the crude division of the
      sleep processes into a few discrete stages, and the total ignorance of spatial
      information are the major drawbacks. It is meaningless to try to improve the
      computerised systems if the algorithms are based on erroneous concepts. Instead,
      the focus should be changed to studies dealing with the identification and
      modelling of true biological sleep-related processes. This work cannot be
      performed without the successful application of computerized methods, some of
      which have been used in related fields but have not yet been applied to sleep
      studies. It is extremely important that basic findings are confirmed with a wide
      variety of methods in several laboratories. The use of predetermined, fixed
      criteria for methods, waveforms, and states too early is scientifically erroneous
      and hazardous. Instead standards should describe the minimum requirements for the
      recording and analysis of the signals in terms of sampling rate, dynamic range,
      linearity, and documentation of the methods used. With the development of better
      technology, these standards ought to be constantly reevaluated and modified. The
      development toward more open commercial digital systems, including standardized
      programming methods and data formats, would have great positive impact to the
      field. These trends have long been established in many other fields of industry.

PMID- 8858493
TI  - The cyclic alternating pattern plays a gate-control on periodic limb movements
      during non-rapid eye movement sleep.
AB  - Periodic limb movements in sleep (PLMS) is a disorder characterized by a cyclic
      pattern of motor phenomena and EEG changes (mostly arousals), both recurring at
      approximately 20- to 40-s intervals. The periodicity of the PLMS phenomena
      recalls the physiological EEG arousal rhythm of non-rapid eye movement (NREM)
      sleep known as the cyclic alternating pattern (CAP). During CAP, arousals and
      arousal-equivalent features do not appear as isolated events but periodically
      intrude (phase A) between intervals of background EEG activity (phase B). Though
      the A phases can be expressed by a variety of EEG patterns, each with a different
      arousal impact on polygraphic parameters, overall CAP is a sequence of biphasic
      cycles reflecting a condition of unstable sleep. Twelve middle-aged PLMS subjects
      complaining of poor sleep were polygraphically compared with 12 age-matched and
      gender-matched healthy volunteers (controls). With respect to controls, the PLMS
      recordings showed an enhancement of the more powerful arousals and presented
      significantly increased amounts of CAP time (+45 min) and CAP rate (+15%). Of all
      the jerks detected in NREM sleep, 92% occurred in CAP, with the great majority of
      limb movements (96%) associated with phase A. Ninety-four percent of the
      nocturnal jerks coupled with phase A started jointly with the onset of the phase
      or when the latter had already begun. In particular, most of the myoclonic events
      (67%) occurred in the first 2.5 s of the A phase. The CAP cycles coupled with
      periodic movements were significantly longer than those without motor events
      (+6.4 s). Compared to the American Sleep Disorders Association's rules for
      scoring EEG arousals, the CAP framework offers a more extensive insight into
      PLMS. In effect, the present study indicates an entrainment of nocturnal
      myoclonus by means of CAP and sheds light on the complex interactions between
      arousal mechanisms and motor phenomena during sleep.

PMID- 8858494
TI  - Triphasic waves in a psychiatric population: a retrospective study.
AB  - In a retrospective study of 15.326 EEGs performed from 1983 to 1992 in a
      psychiatric institute, 83 EEGs (62 patients-13 men and 49 women ranging in age
      from 59 to 90 years, with a mean age of 74 years) had triphasic waves (TWs). All
      62 patients were awake, though they were often confused. Most (n = 56) had
      dementia, usually severe; 15 also had delirium. There were six nondemented
      patients (age range, 59-79 years, with a mean age of 67 years). Infrequent
      etiologies included neuroleptic malignant syndrome (n = 1) and hepatic
      encephalopathy (n = 1); in four, the cause was uncertain, although all were
      receiving lithium. EEG features analyzed included frequency of background
      rhythms, distribution of the TWs, periodicity, and epileptiform abnormalities.
      Background rhythms were slow in all but seven patients (mean, 6.2 +/- 1.7 [SD]
      Hz). TWs were maximal posteriorly in 47 patients and anteriorly in six and were
      diffuse in nine. Neuroimaging studies showed prominent posterior abnormalities in
      only one case. Periodicity was prominent in four patients; in two the TWs were
      maximal anteriorly. Interictal epileptiform activity was present in six, a
      history of seizures in eight, and myoclonus in four. TWs are uncommon in a
      psychiatric population; they occur primarily in elderly, severely demented
      patients. They are usually associated with background slowing, are often maximal
      posteriorly, and occasionally are periodic.

PMID- 8858495
TI  - Recovery from brain-stem lesions involving the nociceptive pathways: comparison
      of clinical findings with laser-evoked potentials.
AB  - Dissociated sensory impairment in brain-stem disorders suggests a lateral lesion
      involving the spinothalamic tract. Evoked potential studies of the somatosensory
      system with standard electrical stimulation (SEP) generally fail to establish
      objective correlates of such sensory deficits, because electrical stimuli
      predominantly activate large myelinated fibers that project into the medial
      lemniscal system. In contrast, laser-evoked potentials (LEPs), in response to
      brief radiant heat pulses, stimulate nociceptive afferents of the superficial
      skin and allow evaluation of thin fiber and spinothalamic tract function. We
      describe the recovery of deficits in pain sensitivity in five patients with
      isolated lateral brain-stem lesions that could be successfully monitored by LEP
      recordings in the acute stage and after intervals ranging from 7 months to 4
      years. Upon first examination, LEPs were abnormal on the affected body side in
      all five cases of lateral medullary syndrome, irrespective of whether the
      etiology was vascular or inflammatory. The degree of recovery of pain sensitivity
      upon reexamination was reflected by the extent of normalization of the LEP. A
      control patient with vascular pontine lacunar stroke had normal LEPs on both
      sides, suggesting preserved spinothalamic conduction. The peak-to-peak amplitude
      of the main LEP component (N250-P400) correlated significantly with clinical pain
      sensitivity scored by standardized sensory testing (r = 0.76, p < 0.01). In
      contrast, early and late SEPs, after standard electrical median or tibial nerve
      stimulation, were normal in all patients, consistent with their intact
      mechanosensitivity. In conclusion, LEP studies allow the status of nociceptive
      function to be objectively and reliably documented on repeated examinations and
      therefore provide a useful supplement to multimodal sensory assessment in brain
      stem disorders.

PMID- 8858496
TI  - Electroencephalographic and polygraphic features of 24-hour recordings in
      sleeping sickness and healthy African subjects.
AB  - Electroencephalographic (EEG) and polygraphic features were analysed in six
      healthy control subjects and eight patients suffering from sleeping sickness
      meningoencephalitis in order to determine possible functional relationships. One
      patient was disqualified because of intermittent metabolic disease. Twenty-four h
      polygraphic recordings-EEG, electrooculography (EOG), electromyography (EMG),
      nasal and buccal air flow, chest respiratory movements-were performed
      continuously both on paper and on cassette tapes. Tapes were played back on paper
      (paper speed: 15 mm/s). Traces were analyzed for normal and pathologic features,
      and transient activation phases and paroxysmal hypnopompic hypersynchrony events
      were counted. During wakefulness, slow theta and delta waves occurred in four
      patients, but alpha reactivity was present. During sleep, normal features were
      seen. However, transient activation phases were decreased in the patients. During
      slow-wave sleep, four patients presented predominantly monophasic frontal delta
      bursts along with paroxysmal hypnopompic hypersynchrony events. In conclusion, in
      sleeping sickness patients, although dampened, the waking process remains
      responsive and slows down only during the late stage of meningoencephalitis.

PMID- 8858497
TI  - Replacement of chordae tendineae with Gore-Tex sutures: a ten-year experience.
AB  - BACKGROUND AND AIMS OF THE STUDY: Expanded polytetrafluoroethylene sutures have
      been used for the replacement of chordae tendineae of the mitral valve since 1985
      at The Toronto Hospital. This study examines the long term results of mitral
      valve repair with chordal replacement with this material. MATERIALS AND METHODS:
      From July 1985 to December 1993, 134 consecutive patients with mitral
      regurgitation due to degenerative disease of the mitral valve underwent mitral
      valve repair with replacement of elongated or ruptured chordae tendineae with one
      to six (mean of 2.8) Gore-Tex sutures. The patients' mean age was 61 years, range
      22-86. In addition to mitral valve repair, 14 patients underwent aortic valve
      surgery, three underwent replacement of the ascending aorta, six underwent
      tricuspid valve repair, nine underwent the maze procedure for atrial
      fibrillation, and 13 underwent coronary artery bypass. The patients were followed
      for between 20 and 116 months, mean 51 months. No patient has been lost to follow
      up. RESULTS: There were one operative and eight late deaths. The actuarial
      survival at eight years was 88% +/- 6%. Four patients required reoperation, one
      for persistent hemolysis and three for recurrent mitral regurgitation. The Gore
      Tex chordae were not responsible for the reoperation in any patient. The freedom
      from reoperation at eight years was 96% +/- 2%. CONCLUSIONS: Expanded
      polytetrafluoroethylene sutures are excellent for chordal replacement during
      mitral valve repair and do not fail during the first decade following surgery.
      This material has allowed us to increase the probability of successful mitral
      valve repair in patients with degenerative disease of the mitral valve and
      prolapse of both leaflets.

PMID- 8858498
TI  - Different applications of ePTFE valve chordae: surgical technique.
AB  - BACKGROUND AND AIMS OF THE STUDY: Artificial chordae made of ePTFE have been used
      for mitral valve repair for 10 years. The positive results obtained in
      experimental and clinical series have led to the extension of their clinical
      indications to mitral valve replacement and tricuspid valve repair. The different
      technical aspects of each of these applications are illustrated. MATERIALS,
      METHODS AND RESULTS: Artificial chordae were implanted in 223 patients undergoing
      mitral valve repair. Seven of them had the valve replaced during the same
      operation due to an unsatisfactory result. Two patients died in the postoperative
      period. During a mean follow up of 38.1 months (range 2-114 months), two more
      patients died, while three reoperations were required; one thromboembolic event
      was reported and the actuarial rates of patient survival and event-free survival
      were 98.0% and 95.8%, respectively, at nine years. In 31 cases of mitral valve
      replacement, with unavoidable removal of the entire subvalvular apparatus,
      ventricular wall-mitral annulus continuity was restored with the insertion of
      artificial chordae. None of these patients died early or during a mean follow up
      of 25.2 months (range 2-110 months), in which only one thromboembolic event was
      reported. In five cases of tricuspid valve insufficiency in which traditional
      techniques of repair were inadequate, valve replacement was avoided with the
      application of artificial chordae. None of these patients experienced any early
      or late complications. CONCLUSION: Based on this experience these procedures are
      safe, reproducible and reliable. They are a valuable support for other
      traditional techniques, allowing the indications for mitral and tricuspid valve
      repair to be extended, and restoring the ventricular-annular continuity in case
      of mitral valve replacement.

PMID- 8858499
TI  - Use of extended polytetrafluoroethylene (ePTFE) chordae to re-establish annular
      papillary connection after mitral valve excision.
AB  - Preserving mitral annular-papillary muscle continuity during mitral valve
      replacement improves left ventricular function and may help prevent ventricular
      rupture. In patients with severe rheumatic or myxomatous mitral valve
      involvement, retaining native chordae may not be possible. We describe a
      technique to recreate the papillary muscle-mitral annular continuity with ePTFE
      sutures when excision of a portion or all of the subvalvular apparatus is
      required.

PMID- 8858500
TI  - The effect of chordal replacement suture length on function and stresses in
      repaired mitral valves: a finite element study.
AB  - BACKGROUND AND AIMS OF THE STUDY: Replacement of ruptured mitral valve chordae
      using expanded polytetrafluoroethylene (ePTFE) sutures is becoming an
      increasingly utilized repair technique. However, setting the proper length of the
      replacement suture is technically challenging, and the effect of a non-optimal
      suture length is undefined. The purpose of this study was to assess how varying
      the length of replacement sutures affects mitral valve function and stresses.
      MATERIALS AND METHODS: We employed a finite element model of the mitral valve
      used extensively in our laboratory. Seven different valve conditions were
      simulated using this model: (i)normal valve, (ii) chordal rupture without repair,
      and (iii-iv) chordal replacement using ePTFE sutures that were equal in length to
      the replaced chordae (equal length), 10% longer (Long10), 3% longer (Long3), 3%
      shorter (Short3), and 10% shorter (Short10) than the replaced chordae. Each model
      was loaded to physiologic pressures. RESULTS: Both the Long10 and chordal rupture
      models achieved complete valve closure, but chordal stresses were nearly double
      normal values. The Long3 model also demonstrated complete valve closure, but
      chordal stresses were increased to only one-third more than normal. Using sutures
      equal to or shorter than the length of the replaced chordae prevented complete
      valve closure, and produced stress concentrations at the anterior leaflet free
      edge. The resulting gaps and stress concentrations were most significant in the
      Short10 model and least significant in the equal length model. CONCLUSIONS: These
      models demonstrate that replacement sutures equal to, or slightly longer than the
      replaced chordae optimize function and stresses in the repaired valve.

PMID- 8858501
TI  - Improving methods of chordal sparing mitral valve replacement. Part I: A new, non
      distorting isovolumic balloon preparation for the left ventricle with intact
      mitral subvalvular apparatus.
AB  - BACKGROUND AND AIMS OF THE STUDY: The conventional isovolumic preparation with a
      single balloon, although employed for many years, distorts the chordae tendineae
      of the intact mitral apparatus. MATERIAL AND METHODS: Anterior balloon (one
      balloon inserted via a slit in the anterior leaflet) and double balloon (two
      balloons through slits in both leaflets) methods were developed and compared to
      the conventional method and natural conditions (LV filled with saline, or 'gold
      standard') in six ex-vivo, non-beating porcine hearts. RESULTS: LV volumes
      measured by the double balloon, anterior balloon, and conventional techniques all
      correlated highly with natural conditions, but the conventional method had a
      lower correlation coefficient (r = 0.99, 0.98, p < 0.0001 and < 0.001; and 0.92 p
      < 0.01, respectively at a left ventricular (LV) pressure of 50 mmHg, while r =
      1.00, 1.00, both p < 0.0001; and 0.92, p < 0.01, respectively at 70 mmHg).
      Epicardial echocardiography revealed that the double balloon technique filled the
      space behind the chordae while maintaining normal chordal geometry, but the
      anterior balloon alone did not (p < 0.001). Similarly, the conventional method
      did not fill the LV outflow tract (p < 0.001) and had a mitral annular shift
      toward the left atrium (p < 0.001). Photography of both leaflets showed that only
      the double balloon method maintained normal geometry as assessed by leaflet
      length ratio; the other methods produced distorted geometry compared to natural
      filling conditions. CONCLUSIONS: With an intact mitral valve, the double balloon
      method provides more precise LV pressure-volume measurements while preserving the
      normal geometry of the chordae tendineae and mitral annulus.

PMID- 8858502
TI  - Anatomic and physiologic bases for the Ross procedure.
AB  - Now that the Ross procedure (RP) has been established as the best method of
      aortic valve replacement (AVR) in several cohorts of patients, it is appropriate
      to analyze the evolution, as well as the anatomic and physiologic bases for it.
      Reviewing the evolution of this operation, one may understand the time lapse
      between its inception and the universal performance of this procedure.
      Experimental work began as early as 1927 by Hochrein. He was followed by the
      Stanford group, Lower in 1960 and 1961, and Pillsbury and Shumway in 1966.
      Successful clinical application by Donald Ross in 14 patients, two in the mitral
      and 12 in the aortic positions, was accomplished in 1967. Several important
      developments followed, including Marcel Geens' study of the blood supply to the
      ventricular septum in 1971 together with the improvement in surgical results
      following the initial experience of Gonzalez-Lavin and Ross. Further developments
      included assessment of the tensile strength of the pulmonary valve (PV) by
      Gorczynski (1982), ability to grow by Murata (1984), a finding of low Ca++
      content of the PV by Livi in 1987 and of excellent hydraulic function by
      Wareesena in 1994. Finally there was universal acceptance by Elkins, Duran, and
      others, culminating with the Ross Registry and the establishment of the Ross
      Colloquium by Oury et al. A review of the anatomical features of the PV are
      compared with those of the aortic valve (AV), including gross anatomy and
      relationship to the sinotubular junction, scan microscopy and anisotropic
      properties of both AV and PV. The blood supply to the ventricular septum will be
      outlined by reviewing Marcel Geens work. The hemodynamics as reported by several
      investigators are reviewed. The clinical evidence of growth by Elkins et al. is
      outlined. Based on this increasing knowledge, indications and contraindications
      for AVR by the RP are discussed.

PMID- 8858503
TI  - A systematic technical approach to the Ross operation.
AB  - The Ross operation is a technically demanding procedure. The pressure on the
      surgeon to produce consistently good results from the very first operation is
      great, since he is not afforded the luxury of a very soft "learning curve", as is
      the case with many technically difficult operations, due to the availability of
      acceptable and safe alternatives for most Ross candidates. We have felt this
      pressure from the outset and this has motivated a commitment to the development
      of a systematic surgical technique in an attempt to achieve consistently
      excellent results. Maintenance of normal autograft spatial geometry after
      translocation to the aortic position is necessary to ensure proper leaflet
      coaptation and to avoid autograft insufficiency, and this is the underlying
      principle upon which this technique is based. Most Ross operations are now
      performed as total aortic root replacements with a free-standing autograft,
      However, the autograft is soft and compliant, and will adapt to the dimensions of
      the more solid tissue into which it is inserted, the aortic annulus proximally
      and ascending aorta distally, and root replacement will not guarantee that normal
      autograft geometry will be maintained unless there is a correct size match
      between the autograft and the aortic annulus and sino-tubular junction, and the
      autograft is not distorted in other ways. A systematic technical approach to the
      Ross operation so that size mismatch is avoided and autograft geometry is
      maintained has been developed and is described in step-by-step detail. In the
      first third of this series of 85 patients, two patients had moderate (2+) and
      three patients had mild (1+) immediate postoperative autograft insufficiency. As
      our understanding of the important sizing and orientation issues has increased
      and the systematic technique has evolved, the incidence of early autograft
      insufficiency has essentially been eliminated. In the latter 2/3 of the series,
      all patients had less than mild autograft insufficiency, except one patient who
      had mild (1+) insufficiency. We believe that these results validate the
      principles on which this systematic technical approach is based and that the
      methods described will help both current and future Ross surgeons perform
      consistently successful operations.

PMID- 8858504
TI  - Autograft failure after the Ross operation in a rheumatic population: pre- and
      postoperative echocardiographic observations.
AB  - BACKGROUND AND AIMS OF THE STUDY: Between January 1990 and July 1995, 108
      patients underwent the Ross operation at our hospital. Most patients (90%) had
      severe aortic regurgitation (AR) in the setting of rheumatic heart disease.
      Although there have been no perioperative or late cardiac deaths, 12 patients
      (11%) developed severe AR requiring reoperation. MATERIAL AND METHODS: We
      performed an extensive and mostly retrospective analysis of echocardiographic
      data on all patients. Preoperative data were analyzed for age, sex, body surface
      area (BSA), size and comparison of the left and right ventricular outflow tracts
      (LVOT, RVOT), left ventricular (LV) size and function, and the presence of
      pulmonary regurgitation (PR) and concomitant mitral regurgitation (MR). Follow up
      data were analyzed for the presence, time of onset, evolution and severity of AR,
      characteristics of the AR jet, anatomic and functional aspects of the aortic root
      and valve, and evolution of LVOT diameter and LV size and function. RESULTS:
      Patients with autograft failure were younger with smaller BSA, larger indexed
      size of LVOT, RVOT and LV, and significantly more had concomitant severe MR.
      Postoperatively they had larger and increasing LVOT size. Trivial or mild AR was
      common and seen in almost all patients, as was a minimal degree of preoperative
      PR. Severe AR developed mostly after the first year of follow up, and reoperation
      was performed within three years in 11/12 patients. In nine patients cusp
      dilatation and prolapse (most frequently of the posterior cusp) was the cause of
      the AR, and rheumatic activity in three. Reoperation was not associated with
      mortality. CONCLUSION: In our population autograft failure seems to be related to
      age, BSA and (indexed) LVOT, RVOT and LV size, but only the presence of
      significant concomitant mitral regurgitation before surgery was identified as a
      predictor for reoperation. Prolapse of one or more cusps were the cause of the AR
      in most patients. The graft is sensitive for recurrent rheumatic activity.

PMID- 8858505
TI  - The use of larger size pulmonary homografts for the Ross operation in children.
AB  - Nine pediatric patients received an adult size cryopreserved pulmonary homograft
      for right ventricular outflow tract reconstruction as part of the Ross procedure.
      The early postoperative results are excellent. It is suggested that a full, adult
      size pulmonary homograft should be used in the future in pediatric patients
      undergoing the Ross procedure.

PMID- 8858506
TI  - False aneurysm: a rare and potentially severe complication after pulmonary
      autograft operation.
AB  - A case of a false aneurysm arising at the proximal suture of an aortic root
      replacement with a pulmonary autograft is presented. This complication did not
      occur in the first postoperative month but was discovered late, and the female
      eight-year-old patient was in an extremely serious condition. She was reoperated
      on an emergency basis but died of acute pulmonary artery hypertension. The
      mechanism of the occurrence of such a case is discussed. In the absence of
      infection, structural weakness of the right ventricular muscle with progressive
      tearing is suggested. Strict and prolonged echocardiographic surveillance after
      the Ross procedure and early reoperation are mandatory.

PMID- 8858507
TI  - Ross operation and right ventricular outflow tract reconstruction with stentless
      xenografts.
AB  - Traditionally a homograft valve is used as a pulmonary replacement device for the
      Ross operation. Right ventricular outflow tract reconstruction during aortic
      valve replacement with an autograft was performed with stentless xenograft valves
      in nine patients. Hemodynamic performance is satisfying, but, long term
      evaluation is needed.

PMID- 8858508
TI  - How to manage patients with severe left ventricular dysfunction and valvular
      regurgitation.
AB  - BACKGROUND AND AIMS OF THE STUDY: The purpose of this study is to analyze
      treatment options for valvular regurgitation with severe left ventricular
      dysfunction. MATERIAL AND METHODS: Results of valvular surgery in 98 patients
      with mitral or aortic regurgitation and severe systolic left ventricular
      dysfunction (LVD) were analyzed. Selection criteria were the absence of
      significant coronary heart disease and a resting ejection fraction (EF) < 40% for
      aortic and < 50% for mitral regurgitation. RESULTS: In patients with aortic
      regurgitation (n = 46) operative mortality was higher but not significantly so
      than in a control group of 238 cases (6.5% vs. 3.4%). The actuarial survival
      rates at five and 10 years were 84% and 55% vs. 84% and 67%, respectively.
      Independent preoperative predictors of severe postoperative LVD were rheumatic
      etiology and increased left ventricular end-systolic diameter. In patients with
      mitral regurgitation (n = 52), operative mortality was not significantly
      different from that of a control group of 273 cases (3.8% vs. 2.6%), whether the
      surgical procedure was valve replacement or valve repair. Perioperative morbidity
      was frequent (30% of cases), mainly low cardiac output, after valve replacement.
      The actuarial survival rates at eight years were respectively for the groups with
      and without LVD: 81% and 89% after valve repair, 60% and 75% after valve
      replacement. Independent predictors of severe postoperative LVD were increased
      left ventricular end-systolic volume and the type of surgery. Better results were
      observed after valve repair. CONCLUSIONS: It is concluded that a low EF is not a
      predictive factor of operative mortality but it influences late survival as do
      the degree of left ventricular dilatation, etiology in aortic and type of surgery
      in mitral regurgitation. Alternatives to valvular surgery have been envisaged but
      information on vasodilators in these patients is scant and results of heart
      transplantation are known only from a few small series.

PMID- 8858509
TI  - Predictors of unsuccessful outcome after percutaneous mitral valvulotomy
      including a new echocardiographic scoring system.
AB  - BACKGROUND AND AIMS OF THE STUDY: Percutaneous mitral valvulotomy has been shown
      to be an accept able alternative to surgery as treatment for selected patients
      with severe mitral stenosis. Uncertainty still exists regarding predictors of
      unsuccessful outcome. MATERIALS AND METHODS: 308 patients with severe mitral
      stenosis underwent Inoue single balloon valvulotomy over a 48-month period and
      were followed up for a mean of 14.5 +/- 16.8 months (range one to 64 months). Two
      hundred and sixty-seven (Group I) improved clinically and remained stable
      throughout the follow up, while subsequent surgery was required in 41 (Group II)
      after 38.2 +/- 143.5 days (range one to 1,212). Clinical and echocardiographic
      parameters of the two groups were compared to find significant predictors of an
      unsuccessful outcome. RESULTS: Significant differences between the groups were
      observed for NYHA class (2.7 +/- 0.6 vs. 2.9 +/- 0.6, p < 0.05), mitral valve
      area (1.0 +/- 0.3 vs. 0.9 +/- 0.2 cm2, p < 0.01), left atrial end-systolic
      dimension by echo (51.3 +/- 8.0 vs. 55.4 +/- 10.2 mm, p < 0.01) and an
      echocardiographic scoring system including grading for eccentricity of the mitral
      orifice and distribution of commissural calcification (7.5 +/- 2.0 for Group I
      and 8.7 +/- 2.0 for Group II, p < 0.001). CONCLUSIONS: Mitral valves that are
      more likely to have an unsuccessful outcome can be identified by hemodynamic,
      clinical and echocardiographic criteria, including grading for eccentricity of
      the mitral orifice and distribution of commissural calcification.

PMID- 8858510
TI  - Severe bioprosthetic tricuspid valve stenosis with systolic antegrade flow across
      the tricuspid valve.
AB  - We report the anatomic and hemodynamic details of severe stenosis of a
      bioprosthetic tricuspid valve studied by transthoracic and transesophageal
      echocardiography. This patient also had antegrade systolic flow across the
      tricuspid valve due to a combination of severe tricuspid valve stenosis and poor
      right ventricular systolic function.

PMID- 8858512
TI  - Quality control of bioprosthetic heart valves by means of holographic
      interferometry.
AB  - BACKGROUND AND AIMS OF THE STUDY: Limited durability of porcine bioprostheses is
      mainly caused by the progressive development of calcification. We tested the
      hypothesis that hidden tissue anomalies or unfavorable stress concentrations of
      commercially available bioprostheses may lead to later calcification and
      dysfunction. Application of holographic interferometry for non-destructive
      testing of biological heart valves enables a full-field analysis of heart valves
      and reveals deformation irregularities of valve tissue. MATERIAL AND METHODS: We
      developed an accelerated calcification protocol for bioprosthetic heart valves
      including an accelerated pulsatile valve tester for simultaneous testing of 10
      heart valves under identical conditions and a rapid synthetic calcification fluid
      containing a final Ca x P of 130 (mg/dl)2 in barbital buffer solution. Ten
      porcine bioprostheses (St. Jude Medical, Bioimplant) were assessed by holographic
      interferometry and subjected to the pulsatile accelerated calcification process.
      Distribution and amount of calcification was evaluated by microradiography after
      12 x 10(6) and 19 x 10(6) cycles, respectively. Areas of irregular fringe
      patterns detected by holography as well as areas of calcification were calculated
      and compared using a personal computer. RESULTS: All tested bioprostheses had
      localized or extended areas with holographic irregularities and the accelerated
      valve testing protocol resulted in even macroscopically visible calcifications at
      various sites. Comparative analysis of the obtained microradiographs revealed
      that 74.2% +/- 6.0% of calcified leaflet areas lay within the previously detected
      holographic anomalies. CONCLUSIONS: Our first results show a strong correlation
      between holographic anomalies and calcification of porcine bioprostheses. We
      conclude that suitable methods for evaluation and quality control of
      bioprosthetic heart valves are available and seem to be predictive with regard to
      valve calcification.

PMID- 8858513
TI  - Development of the Chitra tilting disc heart valve prosthesis.
AB  - BACKGROUND AND AIMS OF THE STUDY: The high prevalence of rheumatic valvular
      disease in the young population and the high cost of imports necessitated the
      development of an Indian valve. The development of a tilting disc prosthesis was
      successfully concluded in February 1995, when the third model completed its
      clinical trial. The tilting disc valve has an integrally machined cobalt alloy
      cage, an ultra high molecular weight polyethylene disc and a polyester suture
      ring. The choice of design was based on its superior hydrodynamics and the age
      distribution of patients, the majority of whom were below 30 years. The polymer
      metal combination was selected for its extremely low wear rate and proven
      durability in the human body. MATERIALS AND METHODS: The hydrodynamic performance
      was tested under steady and pulsatile flow conditions. The accelerated durability
      of nine test valves was evaluated at 800-840 cycles/min for over 350 million
      cycles each. Size 23 mm valves mere implanted in the mitral position of five
      sheep. In a clinical trial, 306 patients with isolated mitral or aortic valve
      replacements were followed up for a total of 371 patient years (mean 1.37 years
      and range 0-4 years). RESULTS: The hydrodynamic performance was comparable to
      that of proven clinical models. The accelerated testing indicated lifetimes in
      excess of 50 years and the animal trials showed the valve to be safe. In the
      clinical trial, there was no incidence of structural failure or paravalvular
      leak. The linearized rate of late thromboembolism was 6.2%/patient-year (pty),
      anticoagulant related hemorrhage 0.54%/pty and infective endocarditis 0.54%/pty.
      At two years, the total actuarial survival was 89.5%. The higher incidence of
      thromboembolism and the very low incidence of anticoagulant related hemorrhage
      illustrate the difficulty in the management of anticoagulant therapy in a
      developing country, while the low incidence of endocarditis reflects their
      greater resistance to infection. CONCLUSION: These data clearly showed the valve
      to be safe and comparable to other similar valves in clinical use.

PMID- 8858514
TI  - The 20 mm Medtronic Hall prosthesis in the small aortic root.
AB  - BACKGROUND AND AIMS OF THE STUDY: The choice of prosthesis becomes crucial in the
      narrow aortic annulus. The 20 mm Medtronic Hall valve has a reduced sewing ring
      that fits in an annulus where only a 19 mm valve would fit. This study assesses
      the hemodynamic performance of this prosthesis at rest and at exercise, and
      compares it with two 19 mm mechanical prostheses. MATERIALS AND METHODS: Forty
      two patients were studied by Doppler echocardiography, a mean of 34 months
      following surgery. Twenty-six had a 19 mm prosthesis implanted (12 standard St.
      Jude Medical and 14 Monostrut valves) and 16 had a 20 mm Medtronic Hall.
      Parameters studied were peak velocity and transvalvular gradient, both at rest
      and at exercise, effective orifice area and valve index. RESULTS: No differences
      were found between the two 19 mm valves, but when compared with the Medtronic
      Hall valve at rest, this valve showed significantly lower peak velocity and
      gradient (2.9 vs. 3.3 m/sec, p < 0.01, and 17 vs. 23 mmHg, p < 0.003,
      respectively) and higher effective orifice area and valve index (1.3 vs. 1.0 cm2,
      p < 0.01 and 0.81 vs. 0.62 cm2, p < 0.006, respectively). There were also
      significant differences under exercise. CONCLUSIONS: The 20 mm Medtronic Hall
      prosthesis shows a significantly better hemodynamic performance, both at rest and
      under exercise, than other, 19 mm mechanical prostheses and represents a superior
      choice in valve replacement with a small aortic root.

PMID- 8858515
TI  - Reoperative mitral valve surgery via right thoracotomy: decreased blood loss and
      improved hemodynamics.

PMID- 8858516
TI  - Study of the antioxidant enzymes in human brain tumors.
AB  - The activities of antioxidant enzymes i.e. Cu, Zn-SOD, Mn-SOD, CAT, and GSH-Px in
      the normal brain and brain tumors, as well as the two varieties of SOD in the
      mitochondria were examined and correlated to the histopathological diagnosis and
      the degree of malignancy of tumors. It was found that these scavenging enzymes of
      oxygen free radicals were expressed with great regularity in brain tumors. Both
      Cu, Zn-SOD and Mn-SOD were decreased in descending order in meningiomas, low
      grade astrocytomas, high grade astrocytomas and medulloblastomas. Furthermore,
      the reduction of Mn-SOD in mitochondria was proportionate to that of the whole
      tissues. While in contrast to the SODs, the CAT levels were significantly
      increased in ascending order in high grade astrocytomas, low grade astrocytomas
      and meningiomas. GSH-Px increased in meningiomas but not in gliomas.

PMID- 8858517
TI  - Comparison of bromodeoxyuridine uptake and MIB 1 immunoreactivity in
      medulloblastomas determined with single and double immunohistochemical staining
      methods.
AB  - We examined the growth potential of 17 medulloblastomas by single and double
      immunohistochemical staining with bromodeoxyuridine (BUdR) and MIB 1, a
      monoclonal antibody for Ki-67 protein, in serial sections of ethanol-fixed,
      paraffin-embedded tissues; we also assessed the heterogeneity of the
      immunoreactivity in the tumors. In the most active areas, the BUdR labeling index
      (LI) was 6.8 to 26.9% (HCl hydrolysis) and 7.5 to 28.8% (microwave heating), and
      the MIB 1 proliferating cell index (PCl) was 14.9 to 56.5%. Linear regression
      analysis showed that the BUdR LI correlated with the MIB 1 PCI (p < 0.001). The
      ratio of MIB 1-positive to BUdR-positive cells was 2.2 +/- 0.4 by both single and
      double staining. BUdR-positive nuclei were heterogeneously distributed in all
      cases, especially in areas with scattered foci of necrosis. Three tumors had
      areas with many MIB 1-positive but few BUdR-positive nuclei; these areas were
      associated with recent tumor necrosis. However, in most of the tumors, the
      densities of BUdR-positive and MIB 1-positive cells changed concomitantly from
      area to area. These changes were clearly shown by double immunostaining. Thus,
      transcapillary passage of BUdR does not appear to be impeded in most
      medulloblastomas. This study suggests that MIB 1 immunostaining provides
      essentially the same data as BUdR labeling for assessing the proliferative
      potential of medulloblastomas.

PMID- 8858518
TI  - The contribution of cytogenetics to the histogenesis of meningeal
      hemangiopericytoma.
AB  - Some controversy has existed regarding the nosology of meningeal
      hemangiopericytoma. In the WHO's classification of 1979 these tumours were
      included as a subgroup of meningiomas, but for some authors, they should not be
      classified as meningiomas. Cytogenetic studies on meningioma demonstrate monosomy
      or partial deletion of chromosome 22 in 60% of these tumors. There have been few
      cytogenetic studies about meningeal hemangiopericytoma. We present here the
      results of cytogenetic studies and fluorescence in situ hybridization in six
      cases of meningeal hemangiopericytoma. In these tumours we have never found
      monosomy 22, but all six cases were hyperdiploid. These cytogenetic data might
      provide additional evidence to differenciate the meningeal hemangiopericytoma
      from the meningioma.

PMID- 8858519
TI  - Lazaroids inhibit proliferation of cultured human astrocytoma cells.
AB  - Lazaroids (or 21-aminosteroids) are potent lipid peroxidation inhibitors and are
      more potent antioxidants than steroids which have been shown to suppress tumor
      proliferation. The effects of two lazaroid compounds (U-75389G and U-83836E) were
      tested on the proliferation of a human brain astrocytoma cell line U-373MG. Both
      lazaroids had dose-dependent growth-inhibitory effects on the proliferation of U
      373MG. For purposes of comparison, two steroids (methylprednisolone and
      dexamethasone) and a highly potent antioxidant (alpha-tocopherol) were tested
      under similar experimental conditions and were found to have antiproliferative
      effects as well, although at higher dose ranges. As cell growth-inhibitors,
      lazaroids are more effective than alpha-tocopherol while they are advantageous
      over glucocorticoids for their actions are devoid of the usual glucocorticoid
      side-effects.

PMID- 8858520
TI  - Effects of hypoxia on drug resistance phenotype and genotype in human glioma cell
      lines.
AB  - Recurrent gliomas are most often treated by chemotherapy. However, these tumors
      typically acquire resistance to most drugs administered, and patients will
      usually die of recurrent tumor. Factors which may play a role include
      overexpression of putative multidrug resistance genes, such as the multidrug
      resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), 06
      alkylguanine, DNA alkyltransferase gene (06MT) and excision repair cross
      complementing gene 1 (ERCC1). Tumor hypoxia has also been shown to be associated
      with drug resistance in other soft tissue tumors. Since gliomas have regions of
      diminished oxygenation, and have clinical resistance to chemotherapy, the
      relationship between phenotypic resistance to chemotherapy after hypoxic exposure
      and expression of drug resistance genes was investigated in glioma cell lines
      (U373 MG, PFAT-MT). After a 24 hour exposure to hypoxia, drugs 1, 3-bis, 2
      chloroethyl-1-nitrosurea (BCNU) and cis-diammine, dichloroplatinum II (CDDP) were
      administered, and cell survival was determined. Hypoxic exposure was associated
      with increased survival of the cell lines after administration of BCNU and CDDP,
      with resistance to BCNU 15 to 30-fold when compared to cells which did not
      undergo hypoxic exposure. Both tumor cell lines also showed some degree of
      resistance to CDDP, although not to the extent of BCNU (2 to 3-fold increased
      resistance). The expression of the drug resistance genes was found to be
      unchanged when comparing cells which had undergone hypoxic exposure and those
      which had not. Thus, hypoxic exposure is associated with substantial drug
      resistance in brain tumor cell lines. The lack of correlation between the induced
      phenotype and known drug resistance genes suggests other mechanisms may be acting
      in these tumors in hypoxic conditions.

PMID- 8858521
TI  - Brain tumor iron uptake measured with positron emission tomography and 52Fe
      citrate.
AB  - Iron and transferrin are required for DNA synthesis and cell division. Cellular
      iron uptake is mediated by transferrin receptors. In order to investigate whether
      iron uptake in brain tumors is associated with their histological grade, we
      studied 24 patients (5 astrocytoma, 11 glioblastoma, 8 meningioma) using positron
      emission tomography and 52Fe-citrate. Tracer uptake from blood into brain and
      tumor tissue was assessed 1. using multiple time graphical analysis yielding a
      measure for unidirectional net tracer uptake (Ki) and 2.) testing a one- and two
      tissue kinetic compartment model, where K1 denotes tracer uptake from blood into
      tissue, k2 efflux from tissue into plasma, and k3 specific tracer binding. In the
      plasma, 52Fe was bound to a 80 kD protein (transferrin). Ki (in units of 10(
      5)/min) was higher in glioblastomas (Ki mean +/- SD 13.6 +/- 6.1) compared with
      astrocytomas (4.8 +/- 3.5, Mann Whitney p = 0.015) and contralateral brain (2.2
      +/- 0.9, Mann Whitney p = 0.009). Highest values were found in meningiomas (no
      blood-brain barrier (BBB); Ki 33.4 +/- 16.5, Mann Whitney p = 0.008 compared with
      glioblastomas). Among the compartment models, fitting with K1 and regional plasma
      volume explained the data best (one-tissue model), data fits were not
      significantly improved by addition of a k2 or k3 parameter. K1 and Ki values were
      significantly correlated (Spearman Rank, p = 0.0006). We conclude that 52Fe
      accumulation in tumors is governed by tracer uptake at the BBB, and does not
      reflect number of transferrin receptors at the level of tumor cells.

PMID- 8858523
TI  - Electric shock-like sensations in 42 cancer patients: clinical characteristics
      and distinct etiologies.
AB  - We retrospectively evaluated 42 consecutive cancer patients manifesting electric
      shock-like sensations. Fourty three percent presented with Lhermitte's sign (LS),
      24% with the previously described outstretching ir. abduction maneuver (OAM) of
      the arms, and 33% had both phenomena. Twenty nine patients had underlying
      polyneuropathy related to cisplatin-based chemotherapy in 27 and to thiamine
      deficiency in 2. Thirtreen patients had myelopathy which was induced by
      radiotherapy in 11. Patients with polyneuropathy manifested both LS and OAM,
      while patients with myelopathy more often presented with LS. Neurologic signs
      suggestive of spinal cord involvement were present in 3 patients with
      polyneuropathy and in 7 of 11 irradiated patients. MRI disclosed cervical spinal
      cord swelling in 3 patients with LS. Prolonged cervical latencies on SSER were
      noted in 5 of 15 patients. All had LS and 3 also had OAM associated with abnormal
      latencies in the brachial plexi. We conclude that LS and OAM are positive sensory
      manifestations of increased mechanosensitivity of the damaged central or
      peripheral sensory axons in the cervico-brachial area. In cancer patients, these
      phenomena largely manifest treatment-induced myelopathy or polyneuropathy.
      Auxillary studies help to confirm diagnosis and to depict the uncommon but
      treatable causes.

PMID- 8858522
TI  - Polyamine metabolism in gliomas.
AB  - Biosynthesis of the polyamines putrescine, spermidine, and spermine has been
      found to be activated in tissues with cellular proliferation. In the present
      study we have investigated polyamine levels and the activity of the first rate
      limiting enzyme ornithine decarboxylase (ODC) in tumour samples obtained during
      operation of 202 patients with gliomas. Biochemical data were closely related to
      the grading of malignancy and to the morphological characteristics of each
      sample. Mean ODC activity was significantly higher in all gliomas as compared to
      peritumoural non-neoplastic brain. Furthermore, it was significantly higher (p <
      or = 0.001) in anaplastic gliomas who grade III and IV (9.0 +/- 9.6 nmol/g/h)
      than in gliomas WHO grade I and II (3.3 +/- 4.2 nmol/g/h). Highest enzyme
      activity (58.5 nmol/g/h) was found in solid and vital parts of malignant tumours,
      whereas predominantly necrotic areas exhibited low ODC activity (< 1 nmol/g/h).
      Thus, intra- and interindividual variability of ODC activity corresponded well to
      histomorphological heterogeneity in high-grade gliomas. Putrescine levels also
      increased with rising grade of malignancy, whereas spermidine and spermine levels
      did not correlate with the histological grading. In conclusion, high ODC activity
      represents a biochemical marker of malignancy in gliomas, but low values do not
      prove benignity. The present study reinforces the need of further and more
      extensive tumour sampling closely related to follow-up investigations in the
      heterogeneous group of gliomas.

PMID- 8858524
TI  - Lhermitte's sign as a presenting symptom of primary spinal cord tumor.
AB  - We describe a previously healthy 29 year-old man who developed Lhermitte's sign,
      a shock-like or electric sensation, transmitted down the spine, which occurred
      during neck flexion or rotation. Evaluation demonstrated an intrinsic, fusiform
      mass extending from c5 to c7. At operation, the mass was completely removed and
      found to be a low-grade ependymoma. The sensory phenomena of Lhermitte's sign
      were most likely caused by tumor-induced distortion and demyelination of cervical
      dorsal column sensory axons. Lhermitte's sign is most prevalent in patients with
      multiple sclerosis, cervical spondylotic myelopathy, cisplatin neurotoxicity,
      cervical radiation injury, and neck trauma. Rarely, Lhermitte's sign occurs with
      spinal cord compression from epidural or subdural tumor. This patients is the
      first reported case of an intrinsic spinal cord tumor to present with Lhermitte's
      sign.

PMID- 8858525
TI  - Epidemiology and etiology of intracranial meningiomas: a review.
AB  - The frequency of meningiomas has been the topic of relatively few reports.
      Hospital-based brain tumor series indicate that the incidence is approximately
      20% of all intracranial tumors; population-based studies indicate an overall
      incidence of 2.3/100,000. Although intracranial tumors as a whole show a higher
      prevalence in males than in females, meningiomas have a 2:1 female-to-male ratio.
      Between Caucasians and Africans, African-Americans, and Asians, certain
      differences also have been noted. Meningiomas in children are rare and differ
      from those in adults and other childhood tumors; they are even more rare in
      infants. Several features indicating etiologic factors have been identified,
      among which are ionizing radiation, head injury, hormones, and other receptor
      binding sites, genetic factors, and viruses. The most common source of exposure
      of the head to ionizing radiation is dental radiographic examination. Since 1922,
      head trauma has been considered a possible risk factor, but recent large studies
      do not support this link. Several factors have prompted studies of estrogens and
      progestogens as risk factors for meningiomas. Other studies have sought to
      determine if certain individuals have an inherited predisposition for developing
      a meningioma and/or if viruses, which may act alone or with other mutagens,
      figure into the formation of a meningioma. The most promising studies are those
      of cytogenetics, and future elucidation of factors associated with the loss of
      one copy of chromosome 22, another phenomenon that has been identified in
      meningiomas, may lead to screening tests and gene therapy.

PMID- 8858526
TI  - The biology of meningiomas.
AB  - Meningiomas, long neglected as a subject for biological studies, are now being
      examined more widely as their potential for clinical recurrence and malignancy
      has been recognized. Most laboratory studies have focused on descriptive analyses
      of the content of various molecules in ex vivo specimens removed at surgery.
      Perturbative experiments using cultured cells are possible, but they are
      complicated by senescence of the cells. The respective importance of the sex
      steroids (estrogen, progesterone, and androgens), classical growth factors,
      angiogenic factors, and proteolytic enzymes in the biological behavior of
      meningiomas is now apparent and is coming under more detailed scrutiny. As
      general theories of neoplasia crystallize in other systems, the ability of
      meningiomas to proliferate, invade, and provoke neovascularization will be better
      understood.

PMID- 8858527
TI  - Pathology of meningiomas.
AB  - Because meningiomas arise from arachnoid cells present in the meninges, they can
      occur in any location where meninges or ectopic meninges exist, such as the nasal
      cavity, the paranasal sinuses, the middle ear, and even the mediastinum. Although
      the tumors may range in appearance from epithelial to mesenchymal, they are
      characterized by a uniform distribution of cells with shapes ranging from
      polygonal epithelial-like to spindled and fusiform. Historically, classification
      of meningiomas has been based upon cell shapes, cell patterns, cell products, or
      stroma, implying clinicopathologic differences among the types. Numerous
      observations have shown that certain conditions may indicate a predisposition for
      developing meningiomas, prompting extensive studies of meningiomas using
      cytogenetic techniques. Meningiomas are common neoplasms arising from the central
      nervous system meninges. They are important because of the morbidity they
      produce. Their critical intracranial and intraspinal locations make diagnosis and
      surgical removal difficult.

PMID- 8858528
TI  - Meningioma in the pediatric population.
AB  - Pediatric meningiomas are rare. They are usually seen in association with
      neurofibromatosis type 2 (NF-2) or following radiation therapy. The tumors are
      more frequently intraventricular, cystic, and infratentorial than are those in
      adult patients. Pathologically they are more histologically aggressive than in
      adults and tend to recur more frequently. Complete resection is the surgical
      goal. The treatment of subtotally resected meningiomas, particularly in NF-2,
      remains controversial.

PMID- 8858529
TI  - Radiology of meningiomas.
AB  - Modern imaging plays an important role in the management of the patient with a
      meningioma. From initial diagnosis to postoperative evaluation and follow-up
      studies, the radiologist must be aware of the various and sometimes atypical
      imaging appearances of meningioma. This is often very satisfying since the
      imaging characteristics of meningioma are usually, but not always, diagnostic.
      This manuscript will briefly review the historical development of the imaging of
      meningioma and then describe the typical and atypical imaging appearances of this
      very common intracranial tumor.

PMID- 8858530
TI  - Surgical treatment of anterior basal meningiomas.
AB  - Meningiomas of the anterior skull base account for 40% of all intracranial
      meningiomas. Of these, almost half are sphenoid wing meningiomas; the other half
      are tuberculum sella tumors or olfactory groove tumors. Anterior clinoidal
      (medial sphenoid wing) meningiomas are a subcategory of the sphenoid wing
      meningiomas; they fall into one of three categories according to the presence of
      an interfacing arachnoidal membrane between the tumor and the cerebral vessels.
      Meningiomas of the tuberculum sella arise from the tuberculum sella, chiasmatic
      sulcus, limbus sphenoidale, and the diaphragma sella; they may extend into both
      optic canals. Olfactory groove meningiomas arise more anteriorly than do the
      tuberculum sella meningiomas and may be symmetrical around the midline or extend
      to one side or the other; at least 15% grow into the ethmoid sinuses. This paper
      addresses the clinical presentation, preoperative evaluation, and surgical
      procedures used for treating tumors of the tuberculum sella, the olfactory
      groove, and the anterior clinoid.

PMID- 8858532
TI  - Radiotherapy for meningiomas.
AB  - Because of a substantial overall recurrence rate of meningiomas, the role of
      surgery as the sole treatment for every case must be evaluated. Also,
      occasionally, the patient's age and/or the location of the tumor precludes
      considering him/her as a candidate for surgery. In these instances, radiotherapy
      or radiosurgery may be advisable. The article presents two cases treated at M.D.
      Anderson Cancer Center, those of a 65-year-old male with a tumor in the left
      temporal lobe and 74-year-old female with a tumor in the right petroclival
      region. It also reviews the roles that radiotherapy plays in treating patients
      with meningiomas. Retrospective analyses of outcomes provide ample evidence that
      conventional radiation after incomplete resection reduces the incidence of
      progression of tumor over a long period. Information on patients who have had
      only external radiation is meager, since most patients have at least a partial
      resection. Complete resection for benign meningiomas is sufficient. For malignant
      meningiomas, adjuvant radiation should be administered, regardless of the extent
      of surgical excision. When surgery poses a high risk of morbidity or mortality,
      radiation therapy and radiosurgery are promising alternatives.

PMID- 8858531
TI  - Petroclival and foramen magnum meningiomas: surgical approaches and pitfalls.
AB  - The management of petroclival and foramen magnum meningiomas has been
      revolutionized by the techniques of cranial base surgery. However, these tumors
      are still among the most difficult cranial base lesions to treat. In this report,
      we discuss the classification, presenting symptoms, preoperative investigation,
      treatment indications, operative approaches and technique, postoperative
      complications and care, and results of surgery of petroclival and foramen magnum
      meningiomas. Careful analysis of tumor- and patient-related factors has helped us
      to predict which features can lead to postoperative problems in patients allowing
      surgeons to appropriately modify their behavior. The application of cranial base
      techniques-combined with new knowledge about the limitations of microsurgical
      resection-can greatly reduce postoperative morbidity in these patients.

PMID- 8858533
TI  - Chemotherapy for meningiomas.
AB  - The most efficacious treatment for meningiomas is surgery. For incompletely
      resected or recurrent tumors, radiotherapy can be given. However, when the
      meningioma is unresectable and/or all other previous treatments have failed,
      immunotherapy or chemotherapy may be considered for malignant tumors and
      immunotherapy and hormone therapy may be considered for benign ones. Various
      chemotherapy treatments that have shown some efficacy in individual cases include
      combinations of Adriamycin and Dacarbazine or Ifosfamide and Mesna. The most
      effective immunotherapy appears to be administration of interferon-alpha, which
      is relatively non-toxic and easily tolerated. However, more studies are needed to
      better define the roles of these agents in the management of a recurrent,
      unresectable, or malignant meningiomas.

PMID- 8858534
TI  - Comparative effects of platelet-derived growth factor-BB and insulin-like growth
      factor-I, individually and in combination, on periodontal regeneration in Macaca
      fascicularis.
AB  - Platelet-derived growth factor (PDGF) and insulin-like growth factor I (IGF-I) in
      combination have previously been shown to enhance periodontal regeneration. The
      objective of this study was to further characterize the biological effects of
      this combination of growth factors in non-human primates and compare the effects
      to those of each growth factor individually. Ligature-induced periodontitis was
      initiated in 10 cynomolgus monkeys. After periodontal lesions were established,
      surgery was performed, and either a methylcellulose gel vehicle or vehicle
      containing 10 micrograms each of either PDGF-BB, IGF-I or both PDGF-BB and IGF-I
      was applied to exposed root surfaces. Biopsies were taken 4 and 12 wk after
      treatment and the extent of periodontal regeneration was assessed by
      histomorphometry. At both 4 and 12 wk vehicle-treated lesions generally revealed
      minimal osseous defect fill (ODF) (8.5 +/- 2.1% and 14.5 +/- 5.7%, respectively)
      and new attachment (NA) (34.1 +/- 5.2% and 26.6 +/- 10.5%, respectively). IGF-I
      treatment did not significantly alter healing compared to vehicle in any
      parameter at both 4 and 12 wk. PDGF-BB-treated sites exhibited significant (p <
      0.05) regeneration of NA (69.6 + 12.0%) at 12 wk; trends for PDGF-BB treatment
      effect were also observed in other parameters at 4 and 12 wk, although these
      increases were not statistically significant. Treatment with PDGF-BB/IGF-I
      resulted in 21.6 +/- 5.1% and 42.5 +/- 8.3% ODF at 4 and 12 wk, respectively, and
      64.1 +/- 7.7% and 74.6 +/- 7.4% NA at 4 and 12 wk, respectively (all
      significantly greater than vehicle, p < 0.05). The results from this study
      demonstrated that: 1) IGF-I alone at the dose tested did not significantly alter
      periodontal wound healing; 2) PDGF-BB alone significantly stimulated NA, with
      trends of effect on other parameters; and 3) the PDGF-BB/IGF-I combination
      resulted in significant increases in NA and ODF above vehicle at both 4 and 12
      wk.

PMID- 8858535
TI  - The synthesis of 5-alpha-dihydrotestosterone from androgens by human gingival
      tissues and fibroblasts in culture in response to TGF-beta and PDGF.
AB  - The effects of TGF-beta and PDGF on the metabolic conversion of 14C-testosterone
      by human gingival tissue (HGT) from 5 subjects was investigated. The metabolic
      conversions in response to TGF-beta and PDGF were also studied in 4-6 cell-lines
      of cultured gingival fibroblasts, using 14C-testosterone and 14C-4
      androstenedione as substrates. Duplicate incubations of HGT were performed in
      Eagle's MEM + 10% FCS and optimal stimulatory concentrations of TGF-beta/PDGF for
      24 h. Similar incubations were performed in duplicate with cell-lines of cultured
      gingival fibroblasts, TGF-beta/PDGF, 14C-testosterone/14C-4-androstenedione in
      Eagle's MEM + 10% FCS. The radioactive metabolites were extracted, separated and
      quantified. With HGT, TGF-beta and PDGF caused 2.5/2-fold increases in DHT
      synthesis (p < 0.1; Wilcoxon signed rank test) and 3.4/2-fold increases in 4
      androstenedione formation (p < 0.1) from 14C-testosterone. PDGF increased DHT and
      testosterone synthesis from 14C-4-androstenedione by 3-fold in gingivae (p <
      0.1). With cell-lines, average values of duplicate incubations showed 2.8/2-fold
      increases in DHT synthesis from 14C-testosterone in response to TGF-beta/PDGF (p
      < 0.1; p < 0.2) and 2.4/2-fold increases in 4-androstenedione synthesis (p < 0.1;
      p < 0.2). With 14C-4-androstenedione as substrate, TGF-beta/PDGF caused 1.6/1.9
      fold increases in DHT synthesis compared with controls (p < 0.05; p < 0.1) and
      1.7/1.5-fold increases in testosterone formation from this substrate (p < 0.05; p
      < 0.1). Due to the strong implications of TGF-beta/PDGF and anabolic androgens on
      matrix repair, significant increases in DHT synthesis from 2 androgenic
      substrates in response to TGF-beta and PDGF are of particular relevance to
      inflammatory repair processes.

PMID- 8858536
TI  - Effect of methyl mercaptan on synthesis and degradation of collagen.
AB  - Measurements of the conversion of [14C]-proline to [14C]-hydroxyproline were
      employed to assess the effect of methyl mercaptan on intra- and extracellular
      metabolism of collagenous proteins in human gingival fibroblast cultures.
      Following a 30-min pulse, 10 ng of methyl mercaptan per ml of 95% air/5% CO2 head
      space suppressed collagen synthesis by 39% and increased the intracellular
      degradation of newly synthesized collagen from 26% to 42%. Parallel cultures
      assayed for proline transport demonstrated a 29% inhibition of [14C]-proline
      uptake. A similar analysis of cultures exposed to methyl mercaptan for 12 h
      revealed an increase in intracellular degradation (20% control vs. 30% test) and
      a marked increase in extracellular collagenolysis (4% control vs. 55% test).
      While pulsing, collagen synthesis was decreased by 39%. Slab gel electrophoresis
      also demonstrated that treatment with methyl mercaptan caused reductions both in
      mature alpha 1 and alpha 2 chains of type I collagen and in type III procollagen.
      Identities of the procollagen species were confirmed by pepsin digestion. Reverse
      transcribed polymerase chain reaction was utilized to compare expression of alpha
      1 chains of type I procollagen with type III procollagen and indicated
      suppression of mRNA synthesis for type III procollagen in cultures exposed to
      methyl mercaptan.

PMID- 8858537
TI  - Sources of error for periodontal probing measurements.
AB  - This study determined the relative contribution to probing measurement
      reliability of several factors, compared with that of random error. Probing
      measurements were performed by examiners properly trained and calibrated. A total
      of 5771 pairs of replicate pocket depth (PD) and relative attachment level (RAL)
      measurements were performed with the Florida Probe. A total of 1488 replicate
      clinical attachment level (CAL) measurements were performed with the North
      Carolina 15 mm probe. In addition, longitudinal replicate measurements of RAL
      were performed at 0 and 12 months on 816 sites in 11 patients utilizing the
      Florida Probe 20 mm disk probe. Measurement reliability with the Florida Probe
      resulted in mean intraexaminer variances of 0.21 and 0.33, for PD and RAL,
      respectively (s.e.m. 0.46 mm for PD and 0.57 mm for RAL). Measurement reliability
      with the conventional probe resulted in mean intra-examiner variances of 0.19 for
      PD and 0.32 for CAL (s.e.m. 0.44 mm and 0.56 mm). Pocket depth contributed to =
      5% of the variability of the intra-examiner variance with both probes with other
      contributing factors being the individual patient, tooth and site location. Mean
      intra-examiner reproducibility for duplicate RAL measurement performed at 0 and
      12 months was 0.24 and 0.19, respectively (s.e.m. 0.49 mm and 0.43 mm). In
      conclusion, a mean intra-examiner variance of < or = 0.24 can be achieved for
      replicate measurements with both electronic and conventional probes for moderate
      and severe periodontitis patients. Individual examiner, individual patient and
      site location contribute up to 10% to the overall variance. Hence, the pattern of
      variability for intra-examiner variance of probing measurements performed with
      either electronic or conventional probes by trained and calibrated examiners is
      mostly random error.

PMID- 8858538
TI  - Influence of conventional forceps extraction and extraction with an extrusion
      instrument on cementoblast loss and external root resorption of replanted monkey
      incisors.
AB  - Cementoblast loss and root resorption on the root surface was registered
      histologically after removal and immediate replantation of maxillary central
      incisors in monkeys (Cecropithecus aethiops). Incisors were removed with either a
      conventional extraction technique using forceps or with a special designed
      extrusion instrument and in both cases teeth were immediately replanted.
      Altogether 18 monkeys were used for the experiments in which 9 monkeys were
      sacrificed after 3 d and 9 animals after 8 wk. Histological analysis was made in
      horizontal sections perpendicular to the long axis of the tooth using either 24
      measuring points or 12 sections. Histometric analysis showed extensive
      cementoblast loss in the periodontal ligament (PDL) and with a maximum of damage
      occurring on the corner surfaces of the root. Extracted teeth showed
      significantly more extensive cementoblast loss than extruded teeth. Root
      resorption was also found in the corner locations and was significantly more
      frequent in extracted than in extruded teeth. There was a similarity in the
      distribution of cementoblast loss and root resorption indicating that root
      resorption develops in the same areas where cementoblast loss takes place, i.e.
      locations that are more compressed during removal of the tooth and must have
      caused by mechanical damage to the PDL exerted on the root surface during tooth
      removal.

PMID- 8858539
TI  - Chymotrypsin-like enzyme secretion is stimulated in cultured epithelial cells
      during proliferation and in response to Actinobacillus actinomycetemcomitans.
AB  - A chymotrypsin-like enzyme was partially purified from culture medium of
      epithelial cells of human skin, human gingiva and porcine periodontal ligament by
      aprotinin-affinity chromatography. The enzyme levels from all three cell types
      were low in quiescent cultures but increased markedly when the cells were allowed
      to proliferate. The biphasic elution profile of the enzyme from the affinity
      column closely matched that of alpha-chymotrypsin and the protein comigrated with
      it on polyacrylamide gels at 27,000 ML. Synthetic substrate tests of purified
      fractions showed strong chymotrypsin-like but no trypsin-like or elastase-like
      activity. Inhibition of protease activity and pH optimum in the range of 7.5-8.0
      were consistent with chymotrypsin-like enzymes. Secreted activity was found to be
      significantly increased by phorbol myristate acetate treatment in a time-course
      that differed from that of elastase-like activity. Keratinocyte growth factor and
      epidermal growth factor but not transforming growth factor-beta increased the
      chymotrypsin-like activity in a concentration-dependent manner. The enzyme
      secretion by epithelial cells was strongly elevated by exposure to 5 of 6
      Actinobacillus actinomycetemcomitans strains isolated from plaque samples of
      juvenile periodontitis patients. These results indicate that chymotrypsin-like
      enzymes are secreted by proliferative phenotypes of normal epithelial cells. This
      enzyme may, therefore, play a role in epithelial physiology and in cell response
      to certain pathogenic bacteria.

PMID- 8858540
TI  - Interleukin-1 alpha produced in human gingival fibroblasts induces several
      activities related to the progression of periodontitis by direct contact.
AB  - Previous observations suggest that interleukin-1 (IL-1) may play an important
      role in the progression of periodontitis. In the present study, we investigated
      whether a cell-associated IL-1 alpha (CAIL-1 alpha) produced in human gingival
      fibroblasts (HGF) induces biological activities related to the progression of
      periodontitis. HGF were treated with recombinant human IL-1 beta (rhIL-1 beta)
      for 12 h. After that, the cell layers of HGF were washed 3 times with fresh
      medium and were then fixed with 1% paraformaldehyde. The fixed cell layers of HGF
      were used for assays for bone resorbing activity, prostaglandin E2 (PGE2)
      production and collagenase activity. Fixed cell layers of HGF treated with rhIL-1
      beta enhanced not only calcium release from BALB/c mouse calvaria but also PGE2
      production and collagenase activity in HGF and human periodontal ligament
      fibroblasts (HPLF) cultured on the fixed cell layers. These activities were
      neutralized by treatment with monoclonal mouse anti-human IL-1 alpha antibody,
      but monoclonal mouse anti-human IL-1 beta antibody showed no effects on these
      activities. The induction of these activities by fixed cell layers of HGF
      required direct contact between the fixed cell layers and the calvaria, HGF, or
      HPLF. These results suggest that CAIL-1 alpha produced in HGF treated with rhIL-1
      beta induces bone resorbing activity, PGE2 production and collagenase activity in
      the target cells by direct contact; CAIL-1 alpha may play an important role in
      the progression of periodontitis.

PMID- 8858541
TI  - Antineutrophil cytoplasmic antibodies: a missing link in the pathogenesis of
      periodontal disease?

PMID- 8858543
TI  - DSM-V: there's work to be done.

PMID- 8858542
TI  - Expression of mineral-associated proteins by periodontal ligament cells: in vitro
      vs. ex vivo.

PMID- 8858544
TI  - Influence of dopaminergic transmission on severity of withdrawal syndrome in
      alcoholism.
AB  - OBJECTIVE: Dysfunction of dopaminergic transmission has been suggested as
      influencing withdrawal syndrome in alcohol-dependent patients. Therefore,
      dopamine levels and sensitivity of dopamine receptors were correlated with the
      severity of withdrawal syndrome in 40 alcoholics. METHOD: Dopamine blood plasma
      levels and apomorphine-induced Growth Hormone (GH) release were measured on the
      first day of detoxification (Day 1) and after 8 days of abstinence (Day 8).
      Severity of withdrawal syndrome was assessed daily by the Clinical Institute
      Withdrawal Assessment (CIWA) score. In the 22 patients (out of the 40) treated by
      chlormethiazole, severity of withdrawal was measured by the required
      chlormethiazole dose. RESULTS: A positive correlation was found between dopamine
      levels on Day 1 and the total CIWA score and necessary chlormethiazole dose,
      respectively. Correlation with the CIWA score was even stronger when the
      sensitivity of post-synaptic dopamine receptors was taken into account. No
      significant correlation between dopamine levels on Day 8 and withdrawal syndrome
      was found. CONCLUSIONS: Our findings indicate an influence of dopaminergic
      transmission on withdrawal syndrome during early withdrawal.

PMID- 8858545
TI  - Longitudinal changes in alcohol and drug use among men seen at a gay-specific
      substance abuse treatment agency.
AB  - OBJECTIVE: This study describes changes over a 12-month period in prevalence and
      frequency of alcohol and other drug use and correlates of change at 12 months in
      a sample of gay/bisexual men entering gay-identified outpatient substance abuse
      treatment. METHOD: A sequential sample of gay/bisexual men (n = 455) were
      recruited for a study in which substance use, sexual risk and psychological
      factors were assessed every 3 months. Changes in substance use were evaluated in
      321 men who used in the 90 days before entering treatment and who completed at
      least one follow-up interview, whether or not they continued in treatment.
      RESULTS: At baseline, 95% of the sample reported alcohol use in the prior 90
      days; 64%, marijuana/hashish use; 46%, amphetamine use; 33%, inhalant nitrites
      use; and 31%, cocaine use. Most men were polydrug users: 10% reported using only
      one drug (including alcohol); 39% used > or = 4 drugs. A marked reduction
      occurred in prevalence of use over time; declines on the order of 50% occurred in
      the first 90 days; prevalence then stabilized in remaining assessments. Frequency
      of usage by those reporting use of any given class of drugs also declined. No
      consistent predictors of reduction or cessation of use across different drug
      categories were found at 1 year. CONCLUSIONS: Substance use declined considerably
      in this sample. Given the scope of substance abuse problems among gay/bisexual
      men, and linkages to the HIV epidemic, considerable resources need to be focused
      on treatment and prevention for gay/bisexual men.

PMID- 8858547
TI  - Determinants of life-course variation in the frequency of alcohol consumption:
      meta-analysis of studies from the collaborative alcohol-related longitudinal
      project.
AB  - OBJECTIVE: This report evaluates the relative contribution of predictors of
      change in the frequency of alcohol consumption among drinkers, based on the
      quantitative synthesis of data from 27 longitudinal studies of the general
      population. The analysis has two objectives: (1) to evaluate the impact of
      selected demographic characteristics on the magnitude and trajectory of change in
      drinking across multiple samples, and (2) to assess the influence of
      methodological characteristics on the consistency of results across studies.
      METHOD: Raw data from studies including two serial measures of the frequency of
      alcohol consumption are analyzed. Fixed, random and mixed effects models for meta
      analysis are used to pool measures across observations and model the influence of
      predictors on variability between results. RESULTS: Gender-based variation in the
      patterning of change is present across all observations, but concentrated in
      early periods of the life course. Age displays significant predictive effects
      across all observations, but statistically uniform results are obtained for
      subjects aged 30 and over. The national origin of study predicts larger amounts
      of variation than do other demographic predictors in the models. Significant
      effects are observed for several methodological characteristics of studies.
      Variation among effect estimates is associated with differences between samples
      in the interval between first and final measurements, the date of first
      measurement (a proxy for the historical context of the sample), the percentage
      retention of subjects between measurements and the time frame of the original
      alcohol measure. CONCLUSIONS: Based on the synthesis of data from multiple
      longitudinal samples, this study (1) characterizes normative developmental
      patterning in the frequency of alcohol consumption and demonstrates the varying
      effects of demographic factors across the life-course: (2) indicates the key
      influence of cultural and historical context on the establishment of drinking
      patterns; and (3) confirms the impact of methodological differences on variation
      in the results of studies.

PMID- 8858546
TI  - Predictors of HIV-related risk behaviors among heterosexuals in alcoholism
      treatment.
AB  - OBJECTIVE: To determine which measures of alcohol and drug use are associated
      with HIV-related sexual risk and protective behaviors. METHOD: Entrants (N = 743,
      72% male) to alcoholism treatment clinics underwent a structured interview
      including an assessment of demographics, substance abuse characteristics and
      sexual behaviors. Associations were examined between alcohol- and drug-related
      behaviors, and demographic variables, with the prevalence of high-risk sexual
      behaviors. RESULTS: Those more likely to use alcohol or drugs when having sex,
      and those who expect to have high-risk sex when they drink alcohol, were more
      likely to engage in high-risk sexual behavior. Measures of severity of alcohol or
      drug problems alone were not consistently related to high-risk or protective
      behaviors. Several other concurrently used measures (such as the Addition
      Severity Index and alcohol expectancies) showed more consistent association with
      high-risk behaviors. There was no apparent reduction in the likelihood of
      practicing risk-reducing behaviors among those more severely addicted and those
      who combined alcohol and/or drugs with sex. CONCLUSIONS: This study suggests that
      sexual risk and protective behaviors are not consistently associated with
      severity of addiction problems. Some measures of alcohol and drug use (i.e., the
      ASI Drug Composite Score and the Enhanced Risk subscale of the alcohol expectancy
      measure) were more consistently related to the specific risk behaviors measured
      than were others (e.g., the ASI Alcohol Composite Score), while most measures
      showed little or no association with protective behaviors.

PMID- 8858548
TI  - Estimating genetic and environmental effects of alcohol use and dependence from a
      national survey: a "quasi-adoption" study.
AB  - OBJECTIVE: A growing number of studies have examined the role of genetic and
      environmental influences on various aspects of alcohol use and abuse for women
      and men. We briefly review relevant twin and adoption studies; overall, these
      studies suggest: (1) both genetic and environmental factors play a role in the
      development of various alcohol-related problems, (2) these factors affect both
      males and females, and (3) genetic factors may be more significant for males than
      females. METHOD: This study is the first to address the question of genetic and
      environmental effects using data from a nationally representative probability
      sample, the National Health Interview Survey, 1988 Alcohol Supplement (NHIS-88A).
      We model the effects of biological family history of alcoholism (FHB) and
      environmental exposure to alcoholism during childhood (FHE) on (1) whether the
      respondent ever drank (current/former drinker), and, given that the respondent is
      a current drinker, (2) whether he or she developed DSM-III-R symptoms of alcohol
      dependence. RESULTS: Results suggest (1) main effects of FHB and FHE on both
      current/former drinker and alcohol dependence and (2) evidence of greater FHB
      effects among males. No other gender differences were detected, and no gene by
      environment interaction effects were found, either for all respondents or by
      gender. CONCLUSIONS: Results are consistent with previous research showing a
      greater effect of genetic risk factors among men than women, yet important
      effects of both environment and genetic factors for both sexes. The study design
      appears to provide an alternative to standard twin and adoption studies as a way
      to separate genetic and environmental risk factors, with both advantages and
      disadvantages compared to such designs. Some of these disadvantages might be
      addressed in questionnaire construction, but some are probably inherent.

PMID- 8858549
TI  - Demographic and psychosocial risk for alcohol use: ethnic differences.
AB  - OBJECTIVE: We examined the influence of demographic variables, and social
      (parents and peers), attitudinal and intentions variables regarding alcohol use
      on actual drinking behavior among Asian and white populations. METHOD: Asian (n =
      148; 79 female, 69 male) and white (n = 132; 72 female, 60 male) college students
      completed a questionnaire. RESULTS: Confirmatory factor analyses revealed that
      social and attitudinal factors reflected a common construct of Psychosocial
      Vulnerability which, in a structural equation model, was significantly predicted
      by ethnicity. The white population was exposed to more psychosocial risks to
      alcohol use compared to the Asian population. Ethnicity, however, did not
      directly predict either drinking intentions or drinking behavior, after the
      effects on Psychosocial Vulnerability were considered. CONCLUSIONS: Our findings
      suggest that ethnic differences in alcohol use between Asians and whites are
      mainly due to different levels of exposure to risk factors. Effective prevention
      programs must consider, not only psychosocial factors, but also certain
      contextual factors such as sex and ethnicity.

PMID- 8858550
TI  - Are women heavier drinkers than we thought they were?
AB  - OBJECTIVE: This study intended (1) to examine whether men are more likely to
      experience "male-type" problems related to drinking and women are more likely to
      encounter "female-type" problems and (2) to discover whether male or female
      collegians have higher blood alcohol concentrations (BACs) at a typical drinking
      session. METHOD: A questionnaire was administered to students enrolled in
      introductory courses in departments of social sciences at two state universities,
      situated in the Midwest and the South, in the spring term of 1994. Of the 2,056
      students who constituted the sample of the present study, about 54% were women
      and 92.6% were white. The subject collegians' BACs during drinking episodes were
      indirectly estimated by three variables-quantity of alcohol consumed, individual
      body weight and duration of drinking session. RESULTS: The data indicate that men
      achieve a higher BAC than do females while drinking. When the incidence of
      various alcohol-related problems (both gender-biased and gender-neutral problems)
      was measured, it was found that, after drinking levels are controlled, gender
      becomes a significant factor in whether some alcohol-related problems will occur.
      CONCLUSIONS: Findings indicate that gender socialization may partly explain
      gender differences in the alcohol-related problems reported.

PMID- 8858551
TI  - The relationship between alcohol consumption and earnings.
AB  - OBJECTIVE: Previous studies of the relation between alcohol consumption and
      earnings have yielded contradictory results. Some studies have shown that
      drinking reduces income while others have shown it has no effect or increases
      earnings. This study uses medical findings concerning the relation between
      alcohol consumption and coronary artery disease to help resolve this
      contradiction and to establish the relationship between the two. METHOD:
      Regression analysis is used to estimate the effects on earnings of various
      traditional variables such as age, education and other socioeconomic variables.
      Using medical findings, a concave quadratic relation between earnings and alcohol
      consumption is tested. This specification is based on the medical finding of the
      curvilinear relation between coronary artery disease (CAD) and alcohol, and the
      notion that CAD will result in lower earnings. The estimates are made from three
      large data sets. RESULTS: The results show that alcohol consumption has a
      significant effect on income. Furthermore, these results support the hypothesis
      that moderate drinkers have greater earnings than either abstainers or abusers.
      This result holds when the effects of ex-drinkers are taken into account
      separately. The levels of highest earnings are consistent with the levels of
      lowest CAD risk (i.e., 2-3.5 drinks per day). CONCLUSIONS: The results help
      resolve apparent contradictions found in the previous literature on earnings and
      alcohol consumption. It is concluded that results of previous studies depended on
      the sample mix of abusers, moderate drinkers and abstainers. Alcohol consumption
      is a significant variable in explaining earnings and the nature of this relation
      is a concave quadratic, similar to that found in medical studies for drinking and
      CAD.

PMID- 8858552
TI  - Suicide attempts and alcohol consumption in an emergency room sample.
AB  - OBJECTIVE: The aim of this study was to obtain an epidemiologic measure of
      association between suicide attempts and alcohol consumption in eight emergency
      room (ER) hospitals. METHOD: All patients were interviewed and breath tested for
      alcohol consumption. The data were analyzed using the case-control methodology.
      Cases were patients (N = 40; 21 male) admitted to ER because of a suicide
      attempt. The control group comprised patients (N = 372) admitted to ER because of
      accidents that are less frequently reported as alcohol related (i.e., workplace
      accidents, animal bites, and recreational accidents, except drowning). RESULTS:
      The proportion of suicide attempts under the effects of alcohol was significantly
      higher than that of the control group. The bivariate odds ratios (and 95%
      confidence intervals) for self-report of alcohol consumption in the 6 hours prior
      to the suicide attempt were: abstainers (baseline); 0.001-100 g of alcohol = 2.01
      (0.44, 7.85); > 100 g = 31.11 (10.13, 98.61). For habitual alcohol consumption;
      abstainers (baseline); 0.001-100 g of alcohol = 0.67 (0.25, 1.77); > 100 g = 1.10
      (0.44, 2.75). For Alco-Sensor: < or = 9 mg of alcohol/100 ml of blood (baseline);
      10.99 mg/100 ml = 8.21 (2.81, 23.73); > or = 100 mg/100 ml = 2.97 (0.42, 15.95).
      Multiple logistic models did not change these findings. CONCLUSIONS: Alcohol
      consumption prior to the suicide attempt is a more important risk factor than the
      habitual alcohol consumption pattern. New research should emphasize life events
      and psychiatric variables and find explanations for differences between the self
      reported and the Alco-Sensor estimates.

PMID- 8858553
TI  - Staging in the onset of DSM-IV alcohol symptoms in adolescents: survival/ hazard
      analyses.
AB  - OBJECTIVE: This research examined staging in the time to onset of DSM-IV alcohol
      symptoms in adolescents. Consistent staging in the onset of symptoms provides
      important tests of the construct validity of diagnostic systems, and aids the
      development of early case identification strategies. METHOD: The Structured
      Clinical Interview for the DSM (SCID), adapted to assess DSM-IV alcohol abuse and
      dependence symptoms, was used to determine time to symptom onset in 102 male and
      97 female adolescent drinkers with and without alcohol use disorders. The sample
      provided a broad range of drinking practices and alcohol-related problems.
      Symptom onset patterns were examined using survival-hazard analyses. RESULTS:
      Survival and hazard data suggested three stages of alcohol problems distinguished
      by time to onset: heavy and heedless drinking with associated social and role
      obligation problems, psychological dependence, and withdrawal. This three-stage
      model fit both the male and female data, and described staging patterns in 70% of
      the subjects. CONCLUSIONS: The symptom onset model suggested a first stage of
      adolescent alcohol symptoms characterized by heavy and heedless drinking with
      associated interpersonal and role obligation problems. The data did not support
      the construct validity of DSM-IV alcohol abuse when applied to adolescents, and
      suggested staging among DSM-IV alcohol dependence symptoms. Implications for the
      diagnosis and early identification of adolescent alcohol problems are discussed.

PMID- 8858554
TI  - Acceptance of moderate drinking by alcoholism treatment services in Canada.
AB  - OBJECTIVE: The present study was conducted to provide a nationwide survey of
      acceptance of nonabstinence goals and related alcoholism treatment practices by
      Canadian alcoholism treatment services. METHOD: A random sample of 335 Canadian
      alcoholism treatment service agencies were mailed a 4-page questionnaire designed
      to assess acceptance of moderate drinking as a drinking goal and related
      alcoholism treatment practices. RESULTS: Acceptance varied by type of service,
      with considerably more acceptance by outpatient programs (62%) and mixed
      inpatient/outpatient programs (43%) than inpatient/detoxification/ correctional
      facilities (27%) and halfway houses (16%). Two-thirds of the respondents who
      reported moderate drinking as unacceptable in their own agencies categorically
      rejected moderation for all alcoholism clients. CONCLUSIONS: Individuals seeking
      services in Canadian alcoholism treatment agencies are more likely to have a
      choice of drinking goals if they present to an outpatient program than a
      residential institution, and Canadian agencies appear more accepting of
      moderation goals than American programs, but less accepting than British and
      Norwegian service agencies.

PMID- 8858555
TI  - Drinking restraint and alcohol-related outcomes: exploring the contributions of
      beverage instructions, beverage content and self-monitoring.
AB  - OBJECTIVE: We examined the role of drinking restraint (temptation and
      restriction), beverage instructions and content and self- monitoring in alcohol
      related outcomes (consumption, subjective intoxication and blood alcohol
      concentration [BAC]) in a sample of moderate-to heavy-drinking young men. METHOD:
      Male social drinkers (N = 132) participated in an individualized taste-rating
      task (TRT), an unobtrusive method for determining ad libitum alcohol consumption.
      Beverages were presented using the format of the balanced placebo design (BPD),
      in which subjects' expectation of an alcoholic versus a non- alcoholic beer was
      crossed with their receipt of an alcoholic versus a nonalcoholic beer. During a
      single 30-minute drinking occasion, each subject sampled two beers and rated
      their taste characteristics on a computer. RESULTS: Consumption during the TRT,
      ratings of subjective intoxication and postdrinking BAC, served as criterion
      variables in regressions in which BPD beverage condition, the two aspects of
      drinking restraint, self-monitoring, and their interactions, served as the
      predictors. The results indicated that TRT consumption was mainly a function of
      the temptation to drink (an aspect of restraint). As expected, assignment to the
      conditions of the BPD predicted subjective intoxication and BAC. Self-monitoring
      did not have an impact on any of the alcohol- related outcomes. CONCLUSIONS: The
      results for TRT consumption suggest that drinking restraint, particularly the
      temptation to drink (i.e., view the regulation of intake as difficult and/or
      drink to repair negative affective states), enhances the consumption of social
      drinkers during a single drinking occasion. Consistent with previous research,
      the conditions of the BPD predicted some alcohol-related outcomes.

PMID- 8858556
TI  - What happened to wine consumption in Iowa following elimination of its retail
      wine monopoly?

PMID- 8858557
TI  - The scientific process works: seven replications now show significant wine sales
      increases after privatization.

PMID- 8858558
TI  - Protective role of curcumin against isoproterenol induced myocardial infarction
      in rats.
AB  - The effect of curcumin on the biochemical changes induced by isoproterenol (ISO)
      administration in rats was examined. ISO (300 mg Kg-1 administered subcutaneously
      twice at an interval of 24 h) caused a decrease in body weight and an increase in
      heart weight, water content as well as in the levels of serum marker enzymes viz
      creatine kinase (CK), lactate dehydrogenase (LDH) and LDH1 isozyme. It also
      produced electrocardiographic changes such as increased heart rate, reduced R
      amplitude and ST elevation. Curcumin at a concentration of 200 mg.Kg-1, when
      administered orally, showed a decrease in serum enzyme levels and the
      electrocardiographic changes got restored towards normalcy. Myocardial infarction
      was accompanied by the disintegration of membrane polyunsaturated fatty acids
      expressed by increase of thiobarbituric acid reactive substance (TBARS), a
      measure of lipid peroxides and by the impairment of natural scavenging,
      characterized by the decrease in the levels of superoxide dismutase, catalase,
      glutathione peroxidase, ceruloplasmin, alpha tocopherol, reduced glutathione
      (GSH) and ascorbic acid. The oral pretreatment with curcumin two days before and
      during ISO administration decreased the effect of lipid peroxidation. It was
      shown to have a membrane stabilizing action by inhibiting the release of beta
      glucuronidase from nuclei, mitochondria, lysosome and microsome. Curcumin pre-
      and co-treatment decreased the severity of pathological changes and thus, could
      have a protective effect against the damage caused by myocardial infarction (MI).

PMID- 8858559
TI  - Role of hydroxyl radical in the oxidant H2O2-mediated Ca2+ release from pulmonary
      smooth muscle mitochondria.
AB  - We sought to investigate the mechanism(s) by which the oxidant H2O2 stimulates
      Ca2+ release from mitochondria of bovine pulmonary vascular smooth muscle tissue
      and to test the hypothesis that hydroxyl radical is involved in this phenomenon.
      Treatment of the smooth muscle tissue with 1 mM H2O2 dramatically stimulated
      hydroxyl radical generation as measured by methane (CH4) production by GLC using
      dimethylsulfoxide (DMSO) as the substrate. Pretreatment of the mitochondria with
      the hydroxyl radical scavanger dimethylthiourea (DMTU) prevented the increase in
      CH4 production caused by H2O2. In the absence of EGTA, H2O2 caused stimulation of
      Ca2+ release from mitochondria occurred with a lag time of about 4 min. Addition
      of EGTA to Ca2+ loaded mitochondria resulted an immediate loss of Ca2+ and that
      has been found to be augmented by H2O2. The release of Ca2+ by H2O2 did not
      appear to occur with concommitant increase in sucrose entry into, K+ release
      from, and swelling of mitochondria when the Ca2+ cycling was prevented by EGTA.
      These observations suggested that H2O2-mediated Ca2+ release from bovine
      pulmonary vascular smooth muscle tissue mitochondria occurred (i) through the
      involvement of hydroxyl radical; (ii) via specific pathway(s); and (iii) did not
      appear to happen primarily via nonspecific "pore' formation.

PMID- 8858560
TI  - Oxidative damage to sarcoplasmic reticulum Ca(2+)-pump induced by
      Fe2+/H2O2/ascorbate is not mediated by lipid peroxidation or thiol oxidation and
      leads to protein fragmentation.
AB  - The major protein in the sarcoplasmic reticulum (SR) membrane is the Ca2+
      transporting ATPase which carries out active Ca2+ pumping at the expense of ATP
      hydrolysis. The aim of this work was to elucidate the mechanisms by which
      oxidative stress induced by Fenton's reaction (Fe(2+)+H2O2-->HO.+OH-+Fe3+) alters
      the function of SR. ATP hydrolysis by both SR vesicles (SRV) and purified ATPase
      was inhibited in a dose-dependent manner in the presence of 0-1.5 mM H2O2 plus 50
      microM Fe2+ and 6 mM ascorbate. Ca2+ uptake carried out by the Ca(2+)-ATPase in
      SRV was also inhibited in parallel. The inhibition of hydrolysis and Ca2+ uptake
      was not prevented by butylhydroxytoluene (BHT) at concentrations which
      significantly blocked formation of thiobarbituric acid-reactive substances
      (TBARS), suggesting that inhibition of the ATPase was not due to lipid
      peroxidation of the SR membrane. In addition, dithiothreitol (DTT) did not
      prevent inhibition of either ATPase activity or Ca2+ uptake, suggesting that
      inhibition was not related to oxidation of ATPase thiols. The passive efflux of
      45Ca2+ from pre-loaded SR vesicles was greatly increased by oxidative stress and
      this effect could be only partially prevented (ca 20%) by addition of BHT or DTT.
      Trifluoperazine (which specifically binds to the Ca(2+)-ATPase, causing
      conformational changes in the enzyme) fully protected the ATPase activity against
      oxidative damage. These results suggest that the alterations in function observed
      upon oxidation of SRV are mainly due to direct effects on the Ca(2+)-ATPase.
      Electrophoretic analysis of oxidized Ca(2+)-ATPase revealed a decrease in
      intensity of the silver-stained 110 kDa Ca(2+)-ATPase band and the appearance of
      low molecular weight peptides (MW < 100 kDa) and high molecular weight protein
      aggregates. Presence of DTT during oxidation prevented the appearance of protein
      aggregates and caused a simultaneous increase in the amount of low molecular
      weight peptides. We propose that impairment of function of the Ca(2+)-pump may be
      related to aminoacid oxidation and fragmentation of the protein.

PMID- 8858562
TI  - Studies on L-threose as substrate for aldose reductase: a possible role in
      preventing protein glycation.
AB  - L-threose is a product of ascorbate oxidation and degradation. By virtue of its
      free aldehyde group it can form Schiff-bases with tissue proteins, altering their
      normal function. In this study, we have examined the possibility of its
      detoxification to L-threitol by aldose reductase in the lens. The rat lens enzyme
      present in fresh homogenate as well as after 100 fold purification was found to
      utilize L-threose with a km of 7.1 x 10(-4) M. The specificity of the reaction
      was affirmed by its inhibition with sorbinil and quercetin, the well known aldose
      reductase inhibitors. Further studies on the role of this enzyme in preventing
      toxicity due to degradation products of ascorbate are in progress.

PMID- 8858561
TI  - Hepatic response to the oxidative stress induced by E. coli endotoxin:
      glutathione as an index of the acute phase during the endotoxic shock.
AB  - Reactive oxygen species are important mediators of cellular damage during
      endotoxic shock. In order to investigate the hepatic response to the oxidative
      stress induced by endotoxin, hepatic and plasma glutathione (total, GSH and
      GSSG), GSSG/GSH ratio as well as Mn-superoxide dismutase and catalase activities
      were determined during the acute and recovery phases of reversible endotoxic
      shock in the rat. A significant increase in liver and plasma total glutathione
      content was observed 5 h after endotoxin treatment (acute phase), followed by a
      diminution of these parameters below control values at 48 h (recovery phase). The
      significant increases of GSSG levels and GSSG/GSH ratio are indicative of
      oxidative stress occurring during the acute phase. Liver Mn-SOD activity showed a
      similar time dependency as the GSSG/GSH ratio; however, a marked decrease in the
      liver catalase activity was observed during the process. These results indicate
      the participation of liver glutathione in the response to endotoxin and the
      possible use of plasma glutathione levels and GSSG/GSH ratio as indicators of the
      acute phase during the endotoxic process.

PMID- 8858563
TI  - Molecular and pharmacological identity of the alpha 2D-adrenergic receptor
      subtype in bovine retina and its photoreceptors.
AB  - The rat cA2-47 gene encodes the pharmacologically defined alpha 2D-adrenergic
      receptor (alpha 2D-AR) subtype. Previously, the expression of its mRNA was shown
      in bovine retina by amplification through the reverse transcription-polymerase
      chain reaction (RT-PCR) of a region corresponding to the rat alpha 2D-AR, amino
      acid (aa) residues 382-439, indicating the presence of this subtype in this
      neural tissue. In the present study, the structure of this gene has been probed
      and the encoded receptor subtype has been characterized in bovine retina and its
      photoreceptor cells. The deduced aa sequence of the two bovine gene fragments, aa
      residues 290-375 and aa residues 392-434, demonstrates 77% overall identity with
      the rat alpha 2D-AR subtype and 80% overall identity with the mouse alpha 2D-AR.
      The receptor encoded by the bovine gene was expressed in the retina and its
      photoreceptors with the typical pharmacological characteristics established for
      the rat alpha 2D-AR subtype: The receptor bound rauwolscine with a KD of 14 nM in
      the retina and with that of 19 nM in the photoreceptor cells; the binding
      association rate constant, k+1, for the ligand was 0.012 min-1, the dissociation
      rate constant, k-1, was 0.14 min-1 and the half-time for dissociation was 5 min.
      Oxymetazoline displaced the bound [3H]-rauwolscine with an EC50 value of 85 nM,
      while SK & F 104078, and prazosin displaced the bound [3H]-rauwolscine with the
      respective IC50 values of 900 nM and 3000 nM. The other alpha 2-AR subtypes 
      alpha 2A-AR, alpha 2B-AR, alpha 2C-AR-were not detected in the retina and its
      photoreceptors. Thus, this study shows that the bovine alpha 2D-AR gene is a
      structural variant of the rat and mouse genes, that the bovine gene encodes the
      typical pharmacologically defined alpha 2D-AR subtype, that this subtype is
      present in its exclusive form in the bovine retina and its photoreceptors, where
      it may be presynaptic in nature.

PMID- 8858565
TI  - Liver and intestinal fatty acid binding proteins in control and TGF beta 1 gene
      targeted deficient mice.
AB  - The effect of transforming growth factor beta-1 (TGF beta 1) expression on fatty
      acid binding proteins was examined in control and two strains of gene targeted
      TGF beta 1-deficient mice. Homozygous TGF beta 1-deficient 129 x CF-1, expressing
      multifocal inflammatory syndrome, had 25% less liver fatty acid binding protein
      (L-FABP) when compared to control mice. The decrease in L-FABP expression was not
      due to multifocal inflammatory syndrome since homozygous TGF beta 1
      deficient/immunodeficient C3H mice on a SCID background had 36% lower liver L
      FABP than controls. This effect was developmentally related and specific to
      liver, but not the proximal intestine, where L-FABP is also expressed. Finally,
      the proximal intestine also expresses intestinal-FABP (I-FABP) which decreased 3
      fold in the TGF beta 1-deficient/immunodeficient C3H mice only. Thus, TGF beta 1
      appears to regulate the expression of L-FABP and I-FABP in the liver and the
      proximal intestine, respectively.

PMID- 8858564
TI  - Regulation of cardiolipin biosynthesis in the heart.
AB  - Cardiolipin is one of the principle phospholipids in the mammalian heart
      comprising as much as 15-20% of the entire phospholipid phosphorus mass of that
      organ. Cardiolipin is localized primarily in the mitochondria and appears to be
      essential for the function of several enzymes of oxidative phosphorylation. Thus,
      cardiolipin is essential for production of energy for the heart to beat. Cardiac
      cardiolipin is synthesized via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol
      pathway. The properties of the four enzymes of the cytidine-5'-diphosphate-1,2
      diacyl-sn-glycerol pathway have been characterized in the heart. The rate
      limiting step of this pathway is catalyzed by the phosphatidic acid: cytidine-5'
      triphosphate cytidylyltransferase. Several regulatory mechanisms that govern
      cardiolipin biosynthesis in the heart have been uncovered. Current evidence
      suggests that cardiolipin biosynthesis is regulated by the energy status
      (adenosine-5'-triphosphate and cytidine-5'-triphosphate level) of the heart.
      Thyroid hormone and unsaturated fatty acids may regulate cardiolipin biosynthesis
      at the level of three key enzymes of the cytidine-5'-diphosphate-1,2-diacyl-sn
      glycerol pathway, phosphatidylglycerol phosphate synthase, phosphatidyl
      glycerolphosphate phosphatase and cardiolipin synthase. Newly synthesized
      phosphatidic acid and phosphatidylglycerol may be preferentially utilized for
      cardiolipin biosynthesis in the heart. In addition, separate pools of
      phosphatidylglycerol, including an exogenous (extra-mitochondrial) pool not
      derived from de novo phosphatidylglycerol biosynthesis, may be utilized for
      cardiac cardiolipin biosynthesis. In several mammalian tissues a significant
      number of studies on polyglycerophospholipid biosynthesis have been documented,
      including detailed studies in the lung and liver. However, in spite of the
      important role of cardiolipin in the maintenance of mitochondrial function and
      membrane integrity, studies on the control of cardiolipin biosynthesis in the
      mammalian heart have been largely neglected. The purpose of this review will be
      to briefly discuss cardiolipin and cardiolipin biosynthesis in some selected
      model systems and focus primarily on current studies involving the regulation of
      cardiolipin biosynthesis in the heart.

PMID- 8858566
TI  - Association of poly(ADP-ribose) polymerase with nuclear subfractions catalyzed
      with sodium tetrathionate and hydrogene peroxide crosslinks.
AB  - Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which catalyzes the
      transfer of ADP-ribose units from NAD+ to a variety of nuclear proteins under the
      stimulation of DNA strand break. To examine its role in DNA repair, we have been
      studying the interaction of PARP with other nuclear proteins using disulfide
      cross-linking, initiated by sodium tetrathionate (NaTT). Chinese Hamster Ovary
      (CHO) cells were extracted sequentially with Nonidet P40 (detergent), nucleases
      (DNase+RNase), and high salt (1.6 M NaCl) with and without the addition of a
      sulfhydryl reducing agent. The residual structures are referred to as the nuclear
      matrix, and are implicated in the organization of DNA repair and replication.
      Treatment of the cells with NaTT causes the crosslinking of PARP to the nuclear
      matrix. Activating PARP by pretreating the cells with H2O2 did not increase the
      cross-linking of PARP with the nuclear matrix, suggesting a lack of additional
      interaction of the enzyme with the nuclear matrix during DNA repair. Both NaTT
      and H2O2 induced crosslinks of PARP that were extractable with high salt. To
      shorten the procedure, these crosslinks were extracted from cells without
      nucleases and high salt treatment, using phosphate buffer. Using western
      blotting, these crosslinks appeared as a smear of high molecular weight species
      including a possible dimer of PARP at 230 kDa, which return to 116 kDa following
      reduction with beta-mercaptoethanol.

PMID- 8858567
TI  - Human recombinant interleukin-1 beta induces thromboxane A2 release in
      polymorphonuclear leukocytes, macrophages and platelets: effect of IL-1 receptor
      antagonist.
AB  - Prostaglandins and thromboxanes (Txs) are produced by polymorphonuclears (PMNs)
      and macrophages (Mphis) in response to various stimuli. PMNs were separated from
      other human blood cells and Mphis were separated from rat peritoneal lavage. In
      this paper we show that human recombinant interleukin-1 (hrIL-1) can stimulate
      the release of thromboxane B2 (TxB2) by PMNs and Mphis. In addition, we have
      shown that aggregation of PMNs may occur when calcium ions (7 mM) and hrIL-1 (100
      ng/ml) are added to the cell preparation, but not when Ca2+ alone, hrIL-1 alone,
      or first hrIL-1 then calcium are added to the cell preparation. The treatment of
      human platelets with hrIL-1 shows that after 15 min incubation TxB2 is released.
      In addition, we compared the aggregation of platelets caused by ADP with that
      caused by hrIL-1. Human recombinant IL-1 at a concentration of 100 ng/ml also
      causes little aggregation of platelets, in this case the aggregation is
      reversible. In conclusion, hrIL-1 beta stimulates TxB2 release in PMNs, Mphis and
      platelets and this effect increases with addition of Ca2+ ions. The mixture of
      hrIL-1 and Ca2+ causes little aggregation of PMNs. In monocyte suspensions,
      pretreated with human recombinant IL-1 receptor antagonist (IL-1ra) 500 ng/ml for
      10 min and then treated with LPS or hrIL-1 beta 10 micrograms/ml, the release of
      TxB2 was partially inhibited. IL-1ra may play a significant role in the control
      of IL-1 and LPS induction in the release of TxB2.

PMID- 8858570
TI  - Nucleotide sequence of a major satellite DNA element isolated from a saltwater
      fish Sillago japonica.
AB  - A member of satellite repetitive DNA was isolated and sequenced from a saltwater
      fish Sillago japonica (Percoidei). This sequence consists of several oligo-dA/dT
      tracts and two inverted repeats which resemble each other. Dot blot hybridization
      analysis using a satellite DNA clone pSJ2 among the species in the suborder
      Percoidei revealed that the pSJ2 sequence was amplified at least after the family
      Sillaginidae had been derived.

PMID- 8858569
TI  - Asymmetric structure of five and six membered DNA hairpin loops.
AB  - The tertiary structure of nucleic acid hairpins was elucidated by means of the
      accessibility of the single-strand-specific nuclease from mung bean. This
      molecular probe has proven especially useful in determining details of the
      structural arrangement of the nucleotides within a loop. In this study 3'
      labeling is introduced to complement previously used 5'-labeling in order to
      assess and to exclude possible artifacts of the method. Both labeling procedures
      result in mutually consistent cleavage patterns. Therefore, methodological
      artifacts can be excluded and the potential of the nuclease as structural probe
      is increased. DNA hairpins with five and six membered loops reveal an asymmetric
      loop structure with a sharp bend of the phosphate-ribose backbone between the
      second and third nucleotide on the 3'-side of a loop. These hairpin structures
      differ from smaller loops with 3 or 4 members, which reveal this type of bend
      between the first and second 3' nucleotide, and resemble with respect to the
      asymmetry anticodon loops of tRNA.

PMID- 8858571
TI  - The effect of matrix attached regions (MAR) and specialized chromatin structure
      (SCS) on the expression of gene constructs in cultured cells and in transgenic
      mice.
AB  - The flanking sequences of several genes have been shown to direct a position
      independent expression of transgenes. Attempts to completely identify the
      insulating sequences have failed so far. Some of these sequences contain a matrix
      attached region (MAR) located in the flanking part of the genes. This article
      will show that the MARs in cultured cells located in the 3' OH region of the
      human apolipoprotein B100 (Apo B100) and within the SV40 genome were unable to
      stimulate and insultate transgene expression directed by the promoters from a
      rabbit whey acidic protein (WAP) gene or from human cytomegalovirus (hCMV) early
      genes. In transgenic mice, the MAR from the Apo B100 and SV40 genes did not
      enhance the expression of a transgene containing the rabbit whey acid protein
      (WAP) promotor, the late gene SV40 intron (VP1 intron), the bovine growth hormone
      (bGH) cDNA and the SV40 late gene terminator. This construct was even toxic for
      embryos. Similarly, the specialized chromatin structure (SCS) from the Drosophila
      87A7 HSP70 gene reduced chloramphenicol acetyl transferase (CAT) activity when
      added between a cytomegalovirus (CMV) enhancer and a Herpes simplex thymidine
      kinase (TK) gene promoter. This inhibitory action was almost complete when a
      second SCS sequence was added before the CMV enhancer. Sequences from the firefly
      luciferase and from the human gene cathepsin D cDNA used as control unexpectedly
      showed a similar inhibitory effect when added to the CMVTKCAT construct instead
      of SCS. When added before the CMV enhancer and after the transcription terminator
      in the CMVTKCAT construct, the SCS sequence was unable to insulate the integrated
      gene as seen by the fact that the level of CAT in cell extracts were by no means
      correlated with the number of copies in individual clones. From these data, it is
      concluded that i) a MAR containing the canonical AT rich sequences does not
      amplify the expression of all gene constructs ii) At rich MAR sequences do not
      have per se an insulating effect iii) Drosophila SCS from the 87A7 HSP70 gene has
      no insulating effect in all gene constructs (at least in mammalian cells) iv) and
      the addition of a DNA fragment between an enhancer and a promoter in a gene
      construct cannot be used as a reliable test to evaluate its insulating property.

PMID- 8858572
TI  - Interaction of Co, Mn, Mg and Al with d(GCGTACGC): a spectroscopic study.
AB  - Spectroscopic study on the interactions of trace elements Co., Mn, Mg and Al with
      d(GCGTACGC) indicated the following: Al and Mg did not alter Tm values. Mn
      enhanced Tm at lower concentration and decreased it at higher concentrations.
      Interestingly Co at higher concentration elevated the Tm. These studies also
      showed lower concentrations of Mn displaced EtBr, whereas Al could displace it at
      higher ionic strength. Mg and Co displaced EtBr fluorescence at moderate
      concentrations. The binding constant values and CD spectra clearly indicated
      strong binding of these elements to DNA.

PMID- 8858573
TI  - Enrichment of chromosome specific hncDNAs by magnetic bead coupled Alu sequences.
AB  - We have employed a strategy for the rapid enrichment of cDNA clones from human
      chromosome 22 utilizing magnetic beads. Starting from a somatic cell hybrid which
      retains chromosome 22 in rodent background, heteronuclear (hn) RNA was
      transcribed into hncDNA using poly dT-primers. Using linker specific primers
      hncDNA was amplified by PCR. To identify chromosome 22 specific hncDNAs a highly
      human specific Alu consensus sequence (PD39) was biotinylated and hybridized to
      the PCR product of the hncDNAs in solution. Hybridized hncDNA-PD39 complexes are
      captured using streptavidin-coated magnetic beads. Hybridized hncDNAs are
      selectively amplified by PCR. To verify the chromosome specificity the hncDNA was
      used as probe for in situ hybridization. Following two rounds of selection with
      magnetic beads there was an increasingly strong hybridization signal on
      chromosome 22. The capturing of hncDNAs by magnetic beads as described in this
      study is faster and more efficient than previously described methods for the
      isolation of chromosome specific hncDNAs. The novel approach has been employed to
      generate hncDNAs highly enriched for chromosome 22 specific sequences.

PMID- 8858574
TI  - Androgen treatment protects mouse liver chromatin from cleavage by endogenous
      nucleases during aging. Androgen and nuclease activity.
AB  - We have examined the endogenous nuclease activity of the liver of intact,
      castrated and testosterone-treated mice of different ages. Both Mg(2+)- and
      Ca(2+)-dependent endogenous nuclease activities decline in old age. Withdrawal of
      the hormone increases nuclease activity in the immature and young. However,
      testosterone administration prevents the digestion of nuclei to different extents
      in all ages. These findings suggest a possible protective role of testosterone in
      the cleavage of liver chromatin by endogenous nucleases during the aging of mice.

PMID- 8858576
TI  - Recombination in mycobacteria.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) is thought
      to infect a quarter of the world's population and accounts for 3 million deaths
      each year. Leprosy, caused by Mycobacterium leprae continues to afflict millions.
      In many countries, the incidence of TB is increasing due to its association with
      acquired immune deficiency syndrome (AIDS) and the emergence of multidrug
      resistance strains of tubercle bacilli. Genes that encode major antigens,
      enzymes, potential virulence determinants and drug resistance in mycobacteria
      have been isolated and characterized; however, further genetic analysis of
      pathogenic mycobacteria has been severely hampered by the difficulty in precisely
      defining the phenotype of both wild-type and mutant genes by utilizing homologous
      recombination to perform allele exchange. Recombination mechanisms have been
      intensely studied in Escherichia coli but it is unclear how far mechanistic
      pathways elucidated in this species are applicable to other organisms, such as
      mycobacteria. The aim of this review is to examine what is currently known about
      homologous recombination in mycobacteria. A model is proposed to account for both
      low levels of homologous recombination and high levels of illegitimate
      recombination found in the tubercle bacillus.

PMID- 8858575
TI  - Autoimmune diseases: nuclear autoantigens can be found at the cell-surface.
AB  - The pathogenesis of autoimmune diseases is only partially understood. In
      particular, the question remains why many nuclear proteins have been identified
      as autoantigens. One possible mechanism for an autoimmune response to nuclear
      proteins involves their exposure to the immune system. In this report we discuss
      currently available data on the exposure of nuclear proteins by expression at the
      cell-surface. Although the pathways of surface expression remain unclear, the
      presence of nuclear proteins at the cell-surface might reflect a pathological
      reaction leading to an exposure of epitopes, e.g. to self-reactive B-cells. It is
      suggested that cell-surface expression of intracellular proteins can contribute
      to the generation of autoimmune diseases.

PMID- 8858577
TI  - Three, four or more: the translational stop signal at length.
AB  - Translational stop signals are defined in the genetic code as UAA, UAG and UGA,
      although the mechanism of their decoding via protein factors is clearly different
      from that of the other codons. There are strong biases in the upstream and
      downstream nucleotides surrounding stop codons. Experimental tests have shown
      that termination-signal strength is strongly influenced by the identity of the
      nucleotide immediately downstream of the codon (+4), with a correlation between
      the strength of this four-base signal and its occurrence at termination sites.
      The +4 nucleotide and other biases downstream of the stop codon may reflect sites
      of contact between the release factor and the mRNA, whereas upstream biases may
      be due to coding restrictions, with the release factor perhaps recognizing the
      final tRNA and the last two amino acids of the polypeptide undergoing synthesis.
      This means that the translational stop signal is probably larger than the triplet
      codon, but its exact length will be clearer when it is known which nucleotides
      are in direct contact with the release factor. Ultimately it will be defined
      exactly when a crystal structure of the release factor with its recognition
      substrate becomes available.

PMID- 8858568
TI  - Signals controlling the expression of PDGF.
AB  - PDGF is an important polypeptide growth factor that plays an essential role
      during early vertebrate development and is associated with tissue repair and
      wound healing in the adult vertebrate. Moreover, PDGF is thought to play a role
      in a variety of pathological phenomena, such as cancer, fibrosis and
      atherosclerosis. PDGF is expressed as a dimer of A and/or B chains, the
      precursors of which are encoded by two single copy genes. Although the PDGF genes
      are expressed coordinately in a number of cell types, they are independently
      expressed in a majority of cell types. The expression of either PDGF gene can be
      affected by very diverse extracellular stimuli and the type of response is
      dependent on the cell type that is exposed to the stimulus. Expression of the
      PDGF chains can be modulated at every imaginable level: by regulating
      accessibility of the transcription start site, by varying the transcription
      initiation rate, by using alternative transcription start sites, by alternative
      splicing, by using alternative polyadenylation signals, by varying mRNA decay
      rates, by regulating efficiency of translation, by protein modification, and by
      regulating secretion. Even upon secretion, the activity of PDGF can be modulated
      by non-specific or specific PDGF-binding proteins. This review provides an
      overview of the cell types in which the PDGF genes are expressed, of the factors
      that are known to affect the expression of PDGF, and of the various levels at
      which the expression of PDGF genes can be regulated.

PMID- 8858578
TI  - Coating the surface: a model for expression of capsular polysialic acid in
      Escherichia coli K1.
AB  - Capsules are well-studied components of the bacterial surface that modulate
      interactions between the cell and its environment. Generally composed of
      polysaccharide, they are key virulence determinants in invasive infections in
      humans and other animals. Genetic determinants involved in capsule expression
      have been isolated from a number of organisms, but perhaps the best characterized
      is the kps cluster of Escherichia coli K1. In this review, the current
      understanding of the functions of the kps gene products is summarized. Further, a
      proposed mechanistic model for capsule expression is presented and discussed. The
      model is based on the premise that the numerous components of the kps cluster
      form a hetero-oligomeric complex responsible for synthesis and concurrent
      translocation of the capsular polysialic acid through sites of inner and outer
      membrane fusion. We view the ATP-binding cassette (ABC) transporter, KpsMT, to be
      central to the functioning of the complex, interacting with the biosynthetic
      apparatus as well as the extracytoplasmic components of the cluster to co
      ordinate synthesis and translocation. The model provides the basis for additional
      experimentation and reflects emerging similarities among systems responsible for
      macromolecular export in Gram-negative bacteria.

PMID- 8858580
TI  - In vitro characterization of constitutive CysB proteins from Salmonella
      typhimurium.
AB  - Expression of the cysteine regulon in Salmonella typhimurium and Escherichia coli
      is controlled by the LysR-type transcriptional activator CysB and by the inducer
      N-acetyl-L-serine. Sulphide and thiosulphate are anti-inducers. Two highly
      purified constitutive CysB proteins, CysB(T149M) and CysB(T149P), were found to
      bind to the cysJIH, cysK and cysP promoters, to activate transcription from the
      cysJIH and cysK promoters in the absence of N-acetyl-L-serine, and to be
      insensitive to the effects of anti-inducers. At 10 mM MgCl2, the in vitro
      transcription activity of CysB(T149M) was maximal without N-acetyl-L-serine, but
      that of CysB(T149P) was increased by inducer. At 2 mM MgCl2, both proteins were
      fully active without inducer. A third mutant protein, CysB(W166R), was totally
      inactive at 10 mM MgCl2, but gave constitutive expression of the cysK and cysJIH
      promoters at 2 mM MgCl2. Surprisingly, wild-type CysB was also constitutive for
      the cysK promoter at 2 mM mgCl2 but not at 10 mM MgCl2; it required inducer for
      cysJIH promoter activation at both concentrations. Mutagenic studies indicated
      that this difference between promoters is due to the distance between activation
      site half-sites, which are separated by 1 bp in the cysJIH promoter and by 2 bp
      in the cysK promoter. We speculate that inducer acts to decrease the distance
      between the binding domains of two CysB subunits that interact with an activation
      site. In vitro activities of wild-type and mutant CysB proteins correlated much
      better with in vivo behaviour at 2 mM than at 10 mM MgCl2, suggesting that the
      former is the more physiological concentration.

PMID- 8858579
TI  - Purification and activities of the Rhodobacter capsulatus RpoN (sigma N) protein.
AB  - The rpoN-encoded sigma factors (sigma N) are a distinct class of bacterial sigma
      factors, with no obvious homology to the major sigma 70 class. The sigma N
      containing RNA polymerase holoenzyme functions in enhancer-dependent
      transcription to allow expression of positively controlled genes. We have
      purified the Rhodobacter capsulatus sigma N protein, which is distinctive in
      lacking an acidic region implicated in the melting of promoter DNA by the
      Escherichia coll sigma N holoenzyme, and may represent a minor subclass of sigma
      N proteins. Assays of promoter recognition and holoenzyme formation and function
      showed that the purified R. capsulatus sigma N protein is distinct in activity
      compared to the enteric proteins, but retains the broad functions described for
      these proteins. As first described for the Klebsiella pneumoniae protein,
      promoter recognition in the absence of core RNA polymerase was detected, but
      contact of certain promoter bases by the R. capsulatus sigma N protein and its
      response to core RNA polymerase was clearly different from that determined for
      the K. pneumoniae and E. coli proteins. Results are discussed in the context of a
      requirement to modulate the activity of the DNA-binding surfaces of sigma N to
      regulate sigma N function. Circular dichroism was used to evaluate the structure
      of the R. capsulatus protein and revealed differences in the tertiary signals as
      compared to the K. pneumoniae protein, some of which are attributable to the DNA
      binding domain of sigma N.

PMID- 8858581
TI  - Definition of a consensus DNA-binding site for the Escherichia coli pleiotropic
      regulatory protein, FruR.
AB  - The FruR regulator of Escherichia coli controls the initiation of transcription
      of several operons encoding a variety of proteins involved in carbon and energy
      metabolism. The sequence determinants of the FruR-binding site were analysed by
      using 6x His-tagged FruR and a series of double-stranded randomized
      oligonucleotides. FruR consensus binding sites were selected and characterized by
      several consecutive rounds of the polymerase chain reaction-assisted binding-site
      selection method (BSS) using nitrocellulose-immobilized DNA-binding protein. FruR
      was demonstrated to require, for binding, an 8 bp left half-site motif and a 3 bp
      conserved right half-site with the following sequence: 5'-GNNGAATC/GNT-3'. In
      this sequence, the left half-site AATC/ consensus tetranucleotide is a typical
      motif of the DNA-binding site of the regulators of the GalR-Lacl family. On the
      other hand, the high degree of degeneracy found in the right half-site of this
      palindrome-like structure indicated that FruR, which is a tetramer in solution,
      interacts asymmetrically with the two half-sites of its operator. However,
      potentially FruR-target sites showing a high degree of symmetry were detected in
      13 genes/operons. Among these, we have focused our interest on the pfkA gene,
      encoding phosphofructo-kinase-1, which is negatively regulated by FruR.

PMID- 8858582
TI  - Rhizobium leguminosarum bv. viciae contains a second fnr/fixK-like gene and an
      unusual fixL homologue.
AB  - Genes of Rhizobium leguminosarum bv. viciae VF39 coding for the regulatory
      elements NifA, FixL and FixK were isolated, sequenced and genetically analysed.
      The fixK-fixL region is located upstream of the fixNOQP operon on the non
      nodulation plasmid pRleVF39c. The deduced amino acid sequence of FixL revealed an
      unusual structure in that it contains a receiver module (homologous to the N
      terminal domain of response regulators) fused to its transmitter domain. An
      oxygen-sensing haem-binding domain, found in other FixL proteins, is conserved in
      R, leguminosarum bv. viciae FixL. R. leguminosarum bv. viciae possesses a second
      fnr-like gene, designated fixK, whose encoded gene product is very similar to
      Rhizobium meliloti and Azorhizobium caulinodans FixK. Individual R. leguminosarum
      bv. viciae fixK and fixL insertion mutants displayed a Fix+ phenotype. A reduced
      nitrogen-fixation activity was found for a R. leguminosarum bv. viciae fnrN
      deletion mutant, whereas no nitrogen-fixation activity was detectable for a
      flxK/fnrN double mutant. The R. leguminosarum bv. viciae nifA gene is expressed
      independently of FixL and FixK under aerobic and microaerobic conditions, whereas
      fixL gene expression is induced under microaerobiosis. Another orf was identified
      down-stream of fixK-fixL and encodes a product which has homology to
      pseudoazurins from different species. Mutation of this azu gene showed that it is
      dispensable for nitrogen fixation.

PMID- 8858583
TI  - The clp (CS31A) operon is negatively controlled by Lrp, ClpB, and L-alanine at
      the transcriptional level.
AB  - Biosynthesis of the Escherichia coli CS31A surface antigen was subject to phase
      variation control and repressed by L-alanine. Nucleotide sequence analysis of the
      clp operon, encoding the biosynthesis of CS31A, revealed the presence of a
      regulatory gene, clpB. The amino acid sequence of the regulatory protein ClpB
      showed similarity to the primary structure of PapB, FaeB and AfaA, involved in
      the regulation of expression of Pap, K88, and Afa-3 fimbriae, respectively. The
      clp regulatory region contained two deoxyadenosine methylase sites (GATC-I and
      GATC-II). The leucine-responsive regulatory protein (Lrp) was required for
      specific methylation inhibition of the GATC-II site. The activity of the clp
      promoter was monitored in a clp-lacZYA single-copy fusion. The cloned DNA used in
      this study did not contain a related papl gene. In these conditions, we showed,
      as expected, that phase variation did not occur. However, transcription of the
      clp operon was negatively controlled by ClpB and Lrp, and was maximal in the
      absence of Dam methylase. In the presence of AfaF, a Papl equivalent, the phase
      variation control was restored. We concluded that two regulatory mechanisms were
      superimposed to control the clp expression. Phase variation, mediated by Lrp and
      a Papl equivalent, controlled the number of cells producing CS31A in a single
      colony. The second mechanism, described in this report, was mediated by ClpB and
      Lrp and controls the level of CS31A produced by a single cell. Furthermore, we
      showed that L-alanine reduced, by about twofold, the clp promoter activity
      independently of a Papl equivalent, ClpB, Lrp or Dam methylase. In addition, the
      presence of L-alanine prevented the phase-variation control mediated by AfaF.

PMID- 8858584
TI  - A stringently controlled expression system for analysing lateral gene transfer
      between bacteria.
AB  - The lateral transfer of genetic information among microorganisms is a major force
      driving the outstanding adaptability of microbial communities to environmental
      changes. Until now little information has been obtained on gene transfer in
      natural ecosystems. We present here a genetic circuit for detecting and
      quantifying horizontal gene transfer from a defined donor microorganism to
      recipient organisms in the absence of selection for a recipient-specific
      phenotype. The system consists of an engineered lacZ (encoding beta
      galactosidase) reporter gene whose expression is controlled by a synthetic
      regulatory element based on a fusion between the Pr promoter-operator from lambda
      bacteriophage and the 5' non-coding leader region of the inp gene encoding the IS
      10 transposase function. Expression of this reporter cassette in the recombinant
      microorganism is completely shut down by two chromosomally encoded trans-acting
      repressors working at the level of transcription (the Cl-EK117 protein from the
      lambda phage), and at the level of translation (the antisense RNA-OUT of the IS
      10 element). When the reporter element is transferred to a different host by any
      mechanism, it escapes repression and becomes expressed. The system was validated
      with Pseudo-monas putida, and conjugational transfer frequencies of the reporter
      element as low as 10(-6) were detected. The modular design and broad host range
      of the genetic circuit, in combination with biomarkers which permit real-time in
      situ detection, will facilitate the monitor-ing of gene flow in a non-disruptive
      manner within the environment.

PMID- 8858585
TI  - A comprehensive set of DnaA-box mutations in the replication origin, oriC, of
      Escherichia coli.
AB  - We probed the complex between the replication origin, oriC, and the initiator
      protein DnaA using different types of mutations in the five binding sites for
      DnaA, DnaA boxes R1-R4 and M: (i) point mutations in individual DnaA boxes and
      combinations of them; (ii) replacement of the DnaA boxes by a scrambled 9 bp non
      box motif; (iii) positional exchange; and (iv) inversion of the DnaA boxes. For
      each of the five DnaA boxes we found at least one type of mutation that resulted
      in a phenotype. This demonstrates that all DnaA boxes in oriC have a function in
      the initiation process. Most mutants with point mutations retained some origin
      activity, and the in vitro DnaA-binding capacity of these origins correlated well
      with their replication proficiency. Inversion or scrambling of DnaA boxes R1 or M
      inactivated oriC-dependent replication of joint replicons or minichromosomes
      under all conditions, demonstrating the importance of these sites. In contrast,
      mutants with inverted or scrambled DnaA boxes R2 or R4 could not replicate in
      wild-type hosts but gave transformants in host strains with deleted or
      compromised chromosomal oriC at elevated DnaA concentrations. We conclude that
      these origins require more DnaA per origin for initiation than does wild-type
      oriC. Mutants in DnaA box R3 behaved essentially like wild-type oriC, except for
      those in which the low-affinity box R3 was replaced by the high-affinity box R1.
      Apparently, initiation is possible without DnaA binding to box R3, but high
      affinity DnaA binding to DnaA box R3 upsets the regulation. Taken together, these
      results demonstrate that there are finely tuned DnaA binding requirements for
      each of the individual DnaA boxes for optimal build-up of the initiation complex
      and replication initiation in vivo.

PMID- 8858586
TI  - FtsZ ring: the eubacterial division apparatus conserved in archaebacteria.
AB  - FtsZ is a tubulin-like protein that is essential for cell division in eubacteria.
      It functions by forming a ring at the division site that directs septation. The
      archaebacteria constitute a kingdom of life separate from eubacteria and
      eukaryotes. Like eubacteria, archaebacteria are prokaryotes, although they are
      phylogenetically closer to eukaryotes. Here it is shown that archaebacteria also
      possess FtsZ and that it is biochemically similar to eubacterial FtsZs.
      Significantly, FtsZ from the archaebacterium Haloferax volcanii is a GTPase that
      is localized to a ring that coincides with the division constriction. These
      results indicate that the FtsZ ring was part of the division apparatus of a
      common prokaryotic ancestor that was retained by both eubacteria and
      archaebacteria.

PMID- 8858587
TI  - Characterization of the fibronectin-attachment protein of Mycobacterium avium
      reveals a fibronectin-binding motif conserved among mycobacteria.
AB  - Mycobacterium avium is an intracellular pathogen and a major opportunistic
      infectious agent observed in patients with acquired immune deficiency syndrome
      (AIDS). Evidence suggests that the initial portal of infection by M. avium is
      often the gastrointestinal tract. However, the mechanism by which the M. avium
      crosses the epithelial barrier is unclear. A possible mechanism is suggested by
      the ability of M. avium to bind fibronectin, an extracellular matrix protein that
      is a virulence factor for several extracellular pathogenic bacteria which bind to
      mucosal surfaces. To further characterize fibronectin binding by M. avium, we
      have cloned the M. avium fibronectin-attachment protein (FAP). The M. avium FAP
      (FAP-A) has an unusually large number of Pro and Ala residues (40% overall) and
      is 50% identical to FAP of both Mycobacterium leprae and Mycobacterium
      tuberculosis. Using recombinant FAP-A and FAP-A peptides, we show that two non
      continuous regions in FAP-A bind fibronectin. Peptides from these regions and
      homologous sequences from M. leprae FAP inhibit fibronectin binding by both M.
      avium and Mycobacterium bovis Bacillus Calmette-Guerin (BCG). These regions have
      no homology to eukaryotic fibronectin-binding proteins and are only distantly
      related to fibronectin-binding peptides of Gram-positive bacteria. Nevertheless,
      these fibronectin-binding regions are highly conserved among the mycobacterial
      FAPs, suggesting an essential function for this interaction in mycobacteria
      infection of their metazoan hosts.

PMID- 8858588
TI  - The role of the AUU initiation codon in the negative feedback regulation of the
      gene for translation initiation factor IF3 in Escherichia coli.
AB  - The expression of the infC gene encoding translation initiation factor IF3 is
      negatively autoregulated at the level of translation, i.e. the expression of the
      gene is derepressed in a mutant infC background where the IF3 activity is lower
      than that of the wild type. The special initiation codon of infC, AUU, has
      previously been shown to be essential for derepression in vivo. In the present
      work, we provide evidence that the AUU initiation codon causes derepression by
      itself, because if the initiation codon of the thrS gene, encoding threonyl-tRNA
      synthetase, is changed from AUG to AUU, its expression is also derepressed in an
      infC mutant background. The same result was obtained with the rpsO gene encoding
      ribosomal protein S15. We also show that derepression of infC, thrS, and rpsO is
      obtained with other 'abnormal' initiation codons such as AUA, AUC, and CUG which
      initiate with the same low efficiency as AUU, and also with ACG which initiates
      with an even lower efficiency. Under conditions of IF3 excess, the expression of
      infC is repressed in the presence of the AUU or other 'abnormal' initiation
      codons. Under the same conditions and with the same set of 'abnormal' initiation
      codons, the repression of thrS and rpsO expression is weaker. This result
      suggests that the infC message has specific features that render its expression
      particularly sensitive to excess of IF3. We also studied another peculiarity of
      the infC message, namely the role of a GC-rich sequence located immediately
      downstream of the initiation codon and conserved through evolution. This sequence
      was proposed to interact with a conserved region in 16S RNA and enhance
      translation initiation. Unexpectedly, mutating this GC-rich sequence increases
      infC expression, indicating that this sequence has no enhancing role. Chemical
      and enzymatic probing of infC RNA synthesized in vitro indicates that this GC
      rich sequence might pair with another region of the mRNA. On the basis of our in
      vivo results we propose, as suspected from earlier in vitro results, that IF3
      regulates the expression of its own gene by using its ability to differentiate
      between 'normal' and 'abnormal' initiation codons.

PMID- 8858589
TI  - Escherichia coli translation initiation factor 3 discriminates the initiation
      codon in vivo.
AB  - In a genetic selection designed to isolate Escherichia coli mutations that
      increase expression of the IS 10 transposase gene (tnp), we unexpectedly obtained
      viable mutants defective in translation initiation factor 3 (IF3). Several lines
      of evidence led us to conclude that transposase expression, per se, was not
      increased. Rather, these mutations appear to increase expression of the tnp'
      'lacZ gene fusions used in this screen, by increasing translation initiation at
      downstream, atypical initiation codons. To test this hypothesis we undertook a
      systematic analysis of start codon requirements and measured the effects of IF3
      mutations on initiation from various start codons. Beginning with an efficient
      translation initiation site, we varied the AUG start codon to all possible codons
      that differed from AUG by one nucleotide. These potential start codons fall into
      distinct classes with regard to translation efficiency in vivo: Class I codons
      (AUG, GUG, and UUG) support efficient translation; Class IIA codons (CUG, AUU,
      AUC, AUA, and ACG) support translation at levels only 1-3% that of AUG; and Class
      IIB codons (AGG and AAG) permit levels of translation too low for reliable
      quantification, importantly, the IF3 mutations had no effect on translation from
      Class I codons, but they increased translation from Class II codons 3-5-fold, and
      this same effect was seen in other gene contexts. Therefore, IF3 is generally
      able to discriminate between efficient and inefficient codons in vivo, consistent
      with earlier in vitro observations. We discuss these observations as they relate
      to IF3 autoregulation and the mechanism of IF3 function.

PMID- 8858590
TI  - The coupling between ftsZ transcription and initiation of DNA replication is not
      mediated by the DnaA-boxes upstream of ftsZ or by DnaA.
AB  - The DnaA protein of Escherichia coli is a multi-functional protein which, In
      addition to promoting initiation of replication, can regulate the initiation or
      termination of transcription of a variety of genes. It acts by binding to DNA at
      a defined sequence, termed a DnaA-box. Three candidate DnaA-boxes which occur
      within the essential cell-division genes, ftsQ and ftsA, have been hypothesized
      to mediate the response of the downstream ftsZ gene to intracellular levels of
      DnaA, and thus to couple the processes of initiation and cell division. We show
      here that, although transcription from promoters upstream of ftsZ is increased
      when initiation of chromosome replication is blocked by DnaA inactivation, this
      response is not mediated by the DnaA-boxes near these promoters, nor is it
      specific to DnaA. We show, furthermore, that mutational inactivation of the
      putative DnaA-binding sites in the fts region of the chromosome does not lead to
      impaired growth or reduced survival of cells.

PMID- 8858591
TI  - Protein F2, a novel fibronectin-binding protein from Streptococcus pyogenes,
      possesses two binding domains.
AB  - Binding of the group A streptococcus (GAS) to respiratory epithelium is mediated
      by the fibronectin (Fn)-binding adhesin, protein F1. Previous studies have
      suggested that certain GAS strains express Fn-binding proteins that are different
      from protein F1. In this study, we have cloned, sequenced, and characterized a
      gene (prtF2) from GAS strain 100076 encoding a novel Fn-binding protein, termed
      protein F2. Insertional inactivation of prtF2 in strain 100076 abolishes its high
      affinity Fn binding. prtF2-related genes exist in most GAS strains that lack
      prtF1 (encoding protein F1) but bind Fn with high affinity. These observations
      suggest that protein F2 is a major Fn-binding protein in GAS. Protein F2 is
      highly homologous to Fn-binding proteins from Streptococcus dysgalactiae and
      Streptococcus equisimilis, particularly in its carboxy-terminal portion. Two
      domains are responsible for Fn binding by protein F2. One domains (FBRD) consists
      of three consecutive repeats, whereas the other domain (UFBD) resides on a non
      repeated stretch of approximately 100 amino acids and is located 100 amino acids
      aminoterminal of FBRD. Each of these domains is capable of binding Fn when
      expressed as a separate protein. In strain 100076, protein F2 activity is
      regulated in response to alterations in the concentration of atmospheric oxygen.

PMID- 8858592
TI  - afsR is a pleiotropic but conditionally required regulatory gene for antibiotic
      production in Streptomyces coelicolor A3(2).
AB  - The N-terminal region of AfsR, a putative pleiotropic regulatory protein for
      antibiotic production in Streptomyces coelicolor A3(2), is homologous to RedD and
      Actil-ORF4, pathway-specific regulatory proteins required for the production of
      the antibiotics undecylprodigiosin (Red) and actinorhodin (Act), respectively.
      The recent identification of afsS, which lies immediately 3' of afsR and which
      stimulates antibiotic production when cloned at high copy number, questioned
      whether afsR was a pleiotropic regulatory gene. In this study we demonstrate that
      multiple copies of afsR can stimulate both Act and Red production and that,
      despite its homology, it cannot substitute for the pathway-specific regulatory
      genes. Moreover, an in-frame deletion that removed most of the afsR coding
      sequence resulted in loss of Act and Red production, and a marked reduction in
      the synthesis of the calcium-dependent antibiotic (CDA), but only under some (non
      permissive) nutritional conditions. Although additional copies of afsR resulted
      in elevated levels of the actII-ORF4 and redD transcripts, transcription of the
      pathway-specific regulatory genes under non-permissive conditions was unaffected
      by deletion of afsR. While afsR may operate independently of the pathway-specific
      regulatory proteins to influence antibiotic production, the activity of ActII
      ORF4 and of RedD under non-permissive conditions could depend on interaction
      with, or modification by, AfsR.

PMID- 8858593
TI  - NodZ of Bradyrhizobium extends the nodulation host range of Rhizobium by adding a
      fucosyl residue to nodulation signals.
AB  - The nodulation genes of rhizobia are involved in the production of the lipo
      chitin oligosaccharides (LCO), which are signal molecules required for nodule
      formation. A mutation in nodZ of Bradyrhizobium japonicum results in the
      synthesis of nodulation signals lacking the wild-type 2-O-methylfucose residue at
      the reducting-terminal N-acetylglucosamine. This phenotype is correlated with a
      defective nodulation of siratro (Macroptilium atropurpureum). Here we show that
      transfer of nodZ to Rhizobium leguminosarum blovar (bv) viciae, which produces
      LCOs that are not modified at the reducing-terminal N-acetylglucosamine, results
      in production of LCOs with a fucosyl residue on C-6 of the reducing-terminal N
      acetylglucosamine. This finding, together with in vitro enzymatic assays,
      indicates that the product of nodZ functions as a fucosyltransferase. The
      transconjugant R. leguminosarum strain producing fucosylated LCOs acquires the
      capacity to nodulate M. atropurpureum, Glycine soja, Vigna unguiculate and
      Leucaena leucocephala. Therefore, nodZ extends the narrow host range of R.
      leguminosarum bv. viciae to include various tropical legumes. However,
      microscopic analysis of nodules induced on siratro shows that these nodules do
      not contain bacteroids, showing that transfer of nodZ does not allow R.
      leguminosarum to engage in a nitrogen-fixing symbiosis with this plant.

PMID- 8858594
TI  - Fucosylation and arabinosylation of Nod factors in Azorhizobium caulinodans:
      involvement of nolK, nodZ as well as noeC and/or downstream genes.
AB  - The DNA region downstream of the nodABCSUIJ operon of Azorhizobium caulinodans
      was further characterized and two new genes, nodZ and noeC were identified in the
      same operon. The A. caulinodans wild-type strain produces a population of Nod
      factors that, at the reducing end, are either unmodified or carry a D-arabinosyl
      and/or an L-fucosyl branch. Nod factors produced by Tn5-insertion mutants in
      nodZ, noeC, and the separate nolK locus, were analysed by thin-layer
      chromatography and mass spectrometry. Fucosylation of Nod factors depended on
      both nodZ and nolK. Arabinosylation depended on noeC and/or downstream genes.
      Protein extracts of A. caulinodans contained an enzymatic activity for fucose
      transfer from GDP-fucose to chitooligosaccharides and to Nod factors. By mutant
      analysis and expression of nodZ in Escherichia coli, the fucosyltransferase
      activity was ascribed to the protein encoded by nodZ. In addition, a Nod factor
      fucosyltransferase activity, independent of nodZ or other known nod genes, was
      detected in A. caulinodans. Finally, on the basis of sequence similarity of the
      nolK gene product, and mass spectrometric analysis of Nod factors produced by a
      nolK mutant, we propose that this gene is involved in the synthesis of GDP
      fucose.

PMID- 8858595
TI  - Common cis-acting elements critical for the expression of several genes of
      Toxoplasma gondii.
AB  - Transient transformation of Toxoplasma using the CAT (chloramphenicol acetyl
      transferase) reporter gene has been used to map promoter elements of four genes
      encoding dense granule proteins (GRA1, GRA2, GRA5 and GRA6). Intense CAT
      activities (GRA1 > GRA5 > GRA2 > GRA6) are detected for constructs containing
      379bp, 276bp, 209bp and 265bp upstream of the transcription start site of the
      GRA1, GRA2, GRA5 and GRA6 genes, respectively. Deletion analysis shows that
      optimal promoter activity of each gene is contained in the proximal region of the
      transcription start site: -129 to -47 for GRA1, -87 to -37 for GRA2, -156 to -30
      for GRA5 and -146 to -27 for GRA6. Quantitative CAT assay and mutation analysis
      show that repeated motifs (A/TGAGACG) found in either orientation with respect to
      transcription are critical elements of these defined promoter regions. We have
      found such sequence elements in the upstream region of other Toxoplasma genes
      such as Tub1 and within the stretch of 27bp repeats of the SAG1 promoter.

PMID- 8858596
TI  - Adaptive mutations: an additional view.

PMID- 8858597
TI  - Transcription of c-mos protooncogene in the pig involves both tissue-specific
      promoters and alternative polyadenylation sites.
AB  - The function of the c-mos gene has been intensively studied, but its role in the
      mammal is still a subject for debate. For this reason, and because the gene is
      regulated posttranscriptionally, further study of the gene from other mammalian
      species is timely. The pig c-mos gene has been cloned, and the genomic sequence
      is presented here. The gene has no introns and shows close similarity to human
      and monkey genes, with striking sequence similarities in both the 5' and 3'
      flanking regions. The significance of this similarity in the context of gene
      regulation is discussed. c-mos expression was found to be restricted to gonadal
      tissues in the pig. The major start sites for transcription initiation in ovary
      and testis were identified by primer extension and found to be distinct, as in
      the mouse. Within the ovary, expression is confined to oocytes. Messenger RNA is
      synthesized in growing oocytes, and remains stable during oocyte maturation, but
      begins to be degraded in electrically stimulated eggs. Unexpectedly, RNase
      protection assays revealed that the 3' ends of transcripts in the pig ovary are
      heterogeneous, and this, together with the identification of three distinct cDNA
      clones, shows that multiple polyadenylation sites are used. The significance of
      these transcripts in terms of translational control is discussed.

PMID- 8858598
TI  - Females of four mole species of genus Talpa (insectivora, mammalia) are true
      hermaphrodites with ovotestes.
AB  - We studied the anatomical, histological, and genetic features of the sexual tract
      in four European mole species of the genus Talpa (Insectivora, mammalia): T.
      occidentalis, T. europaea, T. romana, and T. stankovici. All XY individuals had a
      normal male phenotype, whereas all XX individuals in all four species had
      features that identified them as intersexes. These individuals were nonetheless
      presumed to be functionally fertile females. Intersexuality was manifested mainly
      as gonadal hermaphroditism, with all females possessing bilateral ovotestes. The
      gonads were composed of a small portion of histologically normal ovarian tissue
      and a variably sized, generally large mass of disgenetic testicular tissue,
      accompanied by a small, rudimentary epididymis. The rest of the sexual tract was
      typically female, including oviducts, uterus, and vagina of normal appearance.
      Polymerase chain reaction (PCR) and Southern blotting analyses showed that the
      mammalian testis-determining gene SRY is present in males but not in females.
      Part of the conserved sequence of the mole SRY gene was cloned and sequenced
      after PCR amplification in two of the four mole species (T. occidentalis from
      Spain and T. romana from Italy). Sequences were identical in these two species
      and were very similar to those of the human and mouse SRY gene. Our findings
      constitute the first evidence of the existence of a genus-specific case of true
      hermaphroditism, probably due to a very ancient mutation that fixed in
      populations of the ancestral species from which contemporary moles evolved. The
      possible nature of this mutation is discussed with regard to the cytologic,
      histologic, and genetic features of the gonads in Talpa females.

PMID- 8858599
TI  - Molecular cloning, structural analysis, and expression of carp ZP3 gene.
AB  - Two types of cDNAs coding for a major component of carp egg membrane were clones
      from a carp ovarian cDNA library. They encode polypeptides of 422-424 amino acid
      residues whose sequences are homologous to those of medaka and mammalian ZP3.
      Similar to the mammalian ZP3 genes, carp ZP3 gene also consists of eight exons
      and seven introns. Carp ZP3 genes are 2.9 kb in length and present in multiple
      forms. Carp ZP3 is a glycoprotein of 45 kDa. It was transcribed and translated
      exclusively in oocytes, in contrast with medaka ZP3, which was synthesized in
      liver. The transcription of carp ZP3 starts very early in oogenesis, but
      translation occurs during vitellogenesis, as it is present in vitellogenic but
      not in previtellogenic oocytes. ZP3 content in oocytes increases as
      vitellogenesis proceeds.

PMID- 8858600
TI  - Molecular cloning and characterization of a mouse nuclear orphan receptor
      expressed in embryos and testes.
AB  - A mouse cDNA encoding a putative DNA-binding protein of the zinc-finger type was
      isolated from an E8.5 mouse embryonic cDNA library. Sequence comparison revealed
      a high degree of homology between this mouse cDNA and the human and rat orphan
      receptor Tr2-11 isolated from prostate cDNA libraries. This transcript was
      detected in early-to-midgestation embryos and was seen to level off during later
      stages of development. In adult animals, a high level of expression was detected
      only in the testis, starting at postnatal day 18, a stage when active meiosis
      begins to occur. A specific antibody was raised, and immunoreactive signal was
      specifically located in the adlumenal compartment of the seminiferous tubule,
      where advanced germ cells reside. In mice fed a vitamin A-depleted diet, where
      the testes were depleted of advanced germ cells, expression of this protein could
      not be detected, suggesting a biological relation of this orphan receptor and
      male germ-cell differentiation. Using a retinoic acid response element (RARE)
      containing reporter system, it was demonstrated that expression of this protein
      dramatically repressed both the basal and the retinoic acid (RA)-regulated
      promoter activities of this reporter. Thus, this orphan receptor could play a
      role in modulating both the basic transcription machinery and the RA signalling
      pathway during embryogenesis and male germ-cell differentiation.

PMID- 8858601
TI  - G protein gene expression during mouse oocyte growth and maturation, and
      preimplantation embryo development.
AB  - Fertilization in mammals initiates "egg activation," a series of events leading
      to embryo development. The signal transduction events that occur as a result of
      sperm-egg interactions and that initiate egg activation may be analogous to a
      ligand-receptor-effector pathway, but the details of this signaling pathway are
      poorly understood. Several lines of evidence support a role for guanine
      nucleotide-binding regulatory proteins (G proteins) in mammalian egg activation.
      Prior to initiating studies to examine further the role of specific G proteins in
      sperm-induced mouse egg activation, we needed to define the complement of G
      proteins expressed in the egg. Using a reverse transcription-polymerase chain
      reaction (RT-PCR) assay, the relative levels of mRNAs encoding specific G protein
      alpha, beta, and gamma subunits were determined in meiotically incompetent
      oocytes, fully-grown competent oocytes, metaphase II-arrested eggs, one-, two-,
      and eight-cell embryos, and blastocysts. mRNA transcripts representing all of the
      heterotrimeric G protein families were present at all of the stages examined, and
      all underwent significant changes in their patterns of expression. The following
      heterotrimeric G protein mRNA transcripts were present in oocytes, eggs, or
      preimplantation embryos: G alpha q family (q, 11, and 14), G alpha 12 family (12
      and 13), G alpha i family (i1, i2, i3, t2, z, and s), beta subunits 1, 2, 4, and
      5, and gamma subunits 2, 3, 5, and 7. A recently described large molecular weight
      G protein, G alpha h (Nakaoka et al., 1994: Science 264:1593-1596), was also
      present, G alpha 15, G alpha t1, G alpha olf, G alpha oA, G beta 3, G gamma 1,
      and G gamma 8 mRNA transcripts were not detected using this method. The most
      common pattern of expression observed was a maturation-associated decrease
      followed by an increase after the two-cell stage. Some transcripts, however, were
      expressed at low levels until the eight-cell to blastocyst stages, whereas others
      were expressed at high levels in the oocyte but following maturation declined and
      remained at a low level throughout preimplantation development.

PMID- 8858602
TI  - Species variation in the testicular angiotensin converting enzyme promoter
      studied in transgenic mice.
AB  - We have studied the control of transcription of the testicular angiotensin
      converting enzyme (ACEt) in normal and transgenic mice. Northern analyses,
      including a developmental curve and separated germ cells, for ACEt mRNA suggest
      predominantly post-meiotic expression. Mice transgenic for a construct containing
      the proximal 298 bp of the rabbit ACEt promoter, with chloramphenicol acetyl
      transferase (CAT) as a recorder, showed correct tissue regulation while a 86 bp
      fragment of the promoter led to no expression. Many candidate transacting factor
      binding elements, previously identified as candidate regulators of transcription
      driving spermatogenesis, are scattered across this 298 bp in the rabbit (but not
      the mouse) promoter and may lead to tissue specificity. The recent finding that
      the proximal 91 bp of the mouse ACEt promoter leads to tissue specific expression
      of a recorder gene (Howard et al., 1993) emphasizes the difference between the
      two species and the importance of a cAMP response element (CRE) within this
      fragment for tissue specific expression. This CRE is conserved in the rabbit
      promoters we used.

PMID- 8858603
TI  - Association of rous sarcoma virus DNA with Xenopus laevis spermatozoa and its
      transfer to ova through fertilization.
AB  - Mature Xenopus laevis spermatozoa are capable of binding plasmid pAPrC carrying
      the complete Rous sarcoma virus (RSV) DNA. Each sperm cell associates, on an
      average, with 70-160 molecules of the plasmid DNA in a DNase resistant form, if
      the spermatozoa were exposed to the DNA at a concentration of 1.0-1.4
      micrograms/10(7) sperm cells. Fertilization with pAPrC-treated spermatozoa
      induced developmental malformations in 25-30% of embryos. Immunohistochemical
      analysis of tissue sections from defective animals revealed aberrations in
      myotomal structures, and increased expression of pp60src protein in myoblasts,
      neuronal tube, and epidermis. The presence of characteristic v-src and RSV-long
      terminal repeat (LTR) sequences in X. laevis DNA was detected by PCR analysis.
      Embryonic RNA hybridized with a src-specific and an RSV-LTR specific probes
      indicating expression of the viral DNA. Plasmid DNAs without the v-src gene
      (pATV9) or completely free of any RSV sequences (pBR322) did not induce any
      changes in embryonic development. Our results provide evidence that the pBR322
      cloned DNA form of the RSV genome associates with frog sperm cells in a DNase
      resistant manner suggesting internalization and may be subsequently carried into
      eggs during the process of artificial fertilization. Correlation between the
      defective morphogenesis of X. laevis and increased expression of the src gene as
      well as an interference of RSV DNA with the developmental programs of frog
      embryos are discussed.

PMID- 8858604
TI  - Morphological development, cell number, and allocation of cells to trophectoderm
      and inner cell mass of in vitro fertilized and parthenogenetically developed
      buffalo embryos: the effect of IGF-I.
AB  - The morphology and number of cells in the trophectoderm (TE) and inner cell mass
      (ICM) of buffalo blastocysts derived from in vitro fertilization and cultured in
      the presence or absence of insulin-like growth factor-I (IGF-I) were analyzed by
      differential fluorochrome staining technique. The total cell number (TCN), TE
      number, and ICM cell number were significantly higher in blastocysts developed in
      vitro in the presence of IGF-I as compared to blastocysts developed without IGF-I
      (P < 0.01). It was observed that the buffalo blastocyst took 5-9 days
      postfertilization to develop in vitro. In order to correlate the time required
      for blastocyst development and the allocation of cells to TE and ICM, blastocysts
      were designated as fast (developing on or before day 7) or slow (developing after
      day 7). The TCN, TE, and ICM cells of fast-developing blastocysts cultured in the
      presence of IGF-I were significantly higher than slow-developing blastocysts (P <
      0.01). The blastocysts developed on day 6 had a mean total cell number 118.6 +/-
      21.4, which significantly decreased to 85.6 +/- 17.4, 62.0 +/- 14.5, and 17.0 +/-
      4.0 on days 7, 8, and 9, respectively (P < 0.05). Normal development of buffalo
      embryo showed that, on average, embryos reached compact morula stage at the
      earliest between days 4.5-5.5. Blastocysts developed, at the earliest, between
      days 5.0-6.0, and it took them, on average, 6.5 days to hatch from the zona
      pellucida. TCN, TE, and ICM increased three times from morula to blastocyst;
      however, the proportion of ICM to TCN remained the same, in both embryonic
      stages. TE approximately doubled in hatched blastocysts, as compared to unhatched
      blastocysts (P < 0.05). However, ICM cells were decreased. The time required for
      development of parthenogenetic blastocysts was observed to be greater as compared
      to in vitro fertilized (IVF) blastocysts. The total cell number of
      parthenogenetic blastocysts was 100.8 +/- 11.3, including 59.2 +/- 8.4 cells of
      TE and 42.1 +/- 6.9 cells of ICM.

PMID- 8858605
TI  - Natural and endotoxin-induced atresia of preantral and early antral follicles is
      characterized by DNA internucleosomal cleavage.
AB  - Preantral follicles (PAF) and early antral follicles (EAF) were isolated from
      bovine ovaries and classified under a stereomicroscope as atretic or healthy. The
      atretic follicles were all considered as group I (in vivo atresia), whereas
      healthy follicles were assigned to five groups (group II, in vivo normal control;
      group III, in vitro normal control; group IV, in vitro induced atresia; groups V
      and VI, Lipopolysaccharide (LPS)-induced atresia in vitro). Group I and II
      follicles were immediately snap-frozen (-70 degrees C) until DNA extraction,
      whereas group III-VI follicles were incubated (39 degrees C, 5% CO2, 95% air) for
      periods up to 72 hr under various conditions. Group III follicles were maintained
      in complete medium (M199, bovine calf serum, sodium pyruvate, epidermal growth
      factor, insulin, transferrin, sodium selenite, penicillin, streptomycin, and
      amphotericin), whereas group IV follicles were incubated in the same medium, but
      without serum. Group V and VI follicles were maintained in complete medium, but
      in the presence of LPS (10 or 50 micrograms/ml, respectively). Results showed
      that follicles incubated in the absence of serum and those exposed to both doses
      of LPS became atretic. DNA isolated from all atretic follicles showed
      fragmentation typical of that described for apoptosis; this was also confirmed by
      in situ DNA labeling and histology. Atretic follicles did not produce estradiol
      (P < 0.001), but progesterone values increased with follicle size (P < 0.001) and
      time of incubation (P < 0.001). We concluded that in the absence of serum or in
      the presence of LPS, follicles undergo atresia via apoptosis.

PMID- 8858606
TI  - Endotoxin-induced apoptosis in ovarian follicles is partially blocked by 2
      methylthioATP or 2-chloroATP.
AB  - The purposes of this study were to determine how early in time endotoxin can
      trigger apoptosis of bovine ovarian follicles in vitro, and to further
      characterize if these inductions are mediated via adenine nucleotides and the P2
      purinergic receptors. Healthy preantral and early antral follicles (400 and 700
      microns) isolated from bovine ovaries were sandwiched between two layers of
      collagen gel and incubated (39 degrees C, 5% CO2, 95% air) for various time
      periods up to 72 hr, floating in complete medium with either 2-methylThioATP or
      with 2-ChloroATP, or with or without LPS (10 or 50 micrograms/ml), or with
      combinations of LPS with 2-MethylThioATP or 2-ChloroATP. Data from histological
      examination, and in situ detection of apoptotic DNA cleavage, showed that by 2 hr
      from start of incubation, both doses of LPS had triggered apoptosis of granulosa
      cells (P < 0.001), and simultaneously decreased estradiol concentrations to
      nondetectable levels (P < 0.001), but progesterone values increased (P < 0.001)
      with time of incubation. Both 2-MethylThioATP and 2-ChloroATP inhibited (P <
      0.001) LPS (10 and 50 micrograms/ ml)-induced apoptosis by 30% to 100%. We
      concluded that adenine nucleotides play a fundamental role in endotoxin-induced
      apoptosis/atresia of bovine follicles, probably via the P2 purinergic receptors.
      It is possible that during the first 2 hr of incubation, the apoptotic events
      associated with LPS-induced follicular atresia might not be detectable with the
      procedures used in this study.

PMID- 8858607
TI  - Modifications of the lectin binding pattern in the rat zona pellucida after in
      vivo fertilization.
AB  - The zona pellucida (ZP) is an extracellular matrix surrounding the mammalian
      oocyte. It is involved in the sperm-egg adhesion phenomenon, induces the acrosome
      reaction, and participates in the late blockage to polyspermy. Thus, during the
      process of fertilization the cortical reaction is induced and the biochemical and
      biological properties of the ZP are modified. Some of these changes have been
      suggested to prevent the polyspermy. However, the mechanisms behind most of these
      changes are not well understood. Carbohydrate residues of the ZP glycoproteins
      have been shown to play a key role in the early step of fertilization. In the
      present study, the changes produced in the terminal oligosaccharide sequences of
      the rat ZP glycoproteins after in vivo fertilization were investigated by means
      of lectin-gold cytochemistry. A comparative quantitative analysis of the density
      of labeling in the ZP before and after fertilization was carried out by automatic
      counting of gold particles. The ZP of fertilized and unfertilized eggs were
      labeled by a battery of lectins including PNA, LFA, MAA, AAA, DSA, RCA I, and
      WGA. For all lectin studied in both fertilized and unfertilized eggs the labeling
      was preferentially located in the inner region of the ZP. After fertilization,
      binding of PNA, LFA, MAA, AAA, and DSA decreased in both inner and outer regions
      of the ZP. Labeling of RCA I-binding sites only decreased in the inner ZP,
      whereas reactivity to WGA was increased in the inner ZP, whereas reactivity to
      WGA was increased in the inner area of the ZP. Digestion of the thin-sections
      with neuraminidase prior to labeling with WGA resulted in a decrease of labeling
      for WGA binding sites. However, the labeling density of WGA binding sites was
      similar in both unfertilized and fertilized eggs upon treatment with
      neuraminidase. The present results demonstrate that the oligosaccharide chains
      contained in the rat ZP are modified after fertilization of the oocyte. Cortical
      granules of the oocytes might be involved in these modifications by two
      mechanisms: 1) by hydrolysis of terminal carbohydrate residues of ZP
      glycoproteins by specific glycosidases contained in the granules; and 2) by
      addition of new glycoproteins to the ZP after the exocytosis of the cortical
      granules (cortical reaction).

PMID- 8858608
TI  - Purification, partial characterization, and localization of Sak57, an acidic
      intermediate filament keratin present in rat spermatocytes, spermatids, and
      sperm.
AB  - We have purified a 57 kDa protein (designated Sak57, for spermatogenic cell/sperm
      associated keratin) from sodium dodecyl sulfate-beta-mercaptoethanol (SDS-beta
      ME)-dissociated outer dense fibers isolated from rat sperm tails. Internal
      protein sequence analysis of Sak57 yielded two 15-mer and 10-mer fragments with
      70-100% homology to human, rat, and mouse keratins and corresponding to the 1A
      and 2A regions of the alpha-helical rod domain of keratins. A multiple antigenic
      peptide (MAP) was constructed using the 10-mer amino acid sequence KAQYEDIAQK
      (corresponding to the 2A region) and used as antigen for the production of
      polyclonal antibodies in rabbit. Anti-MAP sera were used for further analysis of
      the biochemical characteristics of Sak57 in testis and sperm tails using
      chromatofocusing, immunoblotting, and [32P] orthophosphate-labeling. We have
      found that rat testis displays two immunoreactive proteins: a soluble 83 kDa
      protein with pl range 5.9-6.3, regarded as a precursor, and both detergent
      insoluble and soluble 57 kDa protein with pl range 5.0-5.9, corresponding to the
      mature form Sak57. The testicular soluble form was phosphorylated. Rat sperm tail
      samples displayed only the Sak57 detergent-insoluble form and its pl was more
      acidic (4.7-4.8). Whole-mount electron microscopy of negatively stained
      preparations of sperm-derived Sak57 resuspended in SDS-beta ME revealed a rod
      shaped pattern. A decrease in the concentration of SDS-beta ME resulted in the
      side-by-side aggregation of rod-shaped Sak57 forming thick bundles. Indirect
      immunofluorescence was used to determine the localization of Sak57 in isolated
      outer dense fibers, epididymal sperm, spermatids, and pachytene spermatocytes.
      Confocal laser scanning microscopy was used to analyze the three-dimensional
      arrangement of Sak57 in pachytene spermatocytes. Isolated outer dense fiber and
      sperm tails displayed an immunoreactive product in the form of linear clusters.
      In elongating spermatids (steps 10-11), Sak57 immunoreactivity was predominant in
      the head region whereas pachytene spermatocytes displayed a cortical cytoplasmic
      distribution. Results of this study demonstrate that Sak57 has the
      characteristics of a keratin intermediate filament and is present during meiotic
      and postmeiotic stages of spermatogenesis.

PMID- 8858609
TI  - Sak57, an acidic keratin initially present in the spermatid manchette before
      becoming a component of paraaxonemal structures of the developing tail.
AB  - We have previously reported that Sak57 (for Spermatogenic cell/Sperm-associated
      keratin of molecular mass 57 kDa) is an acidic keratin found in rat
      spermatocytes, spermatids, and sperm. Sak57 displays conserved amino acid
      sequences found in the 1A and 2A regions of the alpha-helical rod domain of
      keratins in human, rat, and mouse. We now report indirect immunofluorescence,
      confocal laser scanning microscopy and immunogold electron microscopy data
      showing that Sak57 is associated with the microtubular mantie of the manchette, a
      transient microtubular structure largely regarded as formed by tubulin and
      microtubule-associated proteins. The immunocytochemical localization of Sak57 was
      detected with a polyclonal antiserum to a multiple antigenic peptide (MAP)
      containing an amino acid sequence known to be present in the 2A region of the
      alpha-helical rod domain. During spermiogenic steps 8-12, Sak57 immunoreactive
      sites were restricted to microtubular mantie of the manchette which encircles the
      spermatid nucleus during shaping and chromatin condensation. At later stages
      (spermiogenic steps 12-14), Sak57 immunoreactive sites in the spermatid head
      region disappeared gradually as specific immunoreactivity appeared along the
      already assembled axoneme of the developing spermatid tail. Immunogold electron
      microscopy confirmed the presence of Sak57 immunoreactivity among microtubules of
      the manchette and on outer dense fibers and the longitudinal columns linking the
      ribs of the fibrous sheath. Mature spermatids (spermiogenic step 19) displayed
      tails with an immunofluorescent banding pattern contrasting with the lack of
      Sak57 immunoreactivity in the head region. Results from this study suggest that,
      during early spermiogenesis, a microtubular-Sak57 scaffolding is associated with
      the spermatid nucleus during shaping and chromatin condensation. During late
      spermiogenesis, the dispersion of the manchette coincides with the progressive
      visualization of Sak57 in the paraaxonemal outer dense fibers and longitudinal
      columns of the fibrous sheath in the developing spermatid tail.

PMID- 8858610
TI  - Localization and function of tyrosine-phosphorylated protein in pig oocytes.
AB  - Several proteins with phosphorylated tyrosine residues have been shown to be
      closely involved in the control meiotic nuclear division. We identified a 42-kD
      protein in pig oocytes, using a polyclonal antibody to a synthetic
      phosphotyrosine construct that increases significantly in amount after 12 hr of
      maturation culture, and is discretely localized to condensing and condensed
      chromosomes. However, since microinjection of the antibody into oocytes blocks
      spindle formation, the role of this protein appears to be at that stage rather
      than directly in chromosome condensation. Specificity of action of the 42-kD
      protein indicates that it may be a phosphorylation-dependent component necessary
      for successful spindle assembly.

PMID- 8858611
TI  - Ovarian control of very low sperm/egg ratios at the commencement of mammalian
      fertilisation to avoid polyspermy.
AB  - This essay considers the means whereby sperm/egg ratios close to unity are
      generated during the initial stages of fertilisation in placental mammals. Pre
      ovulatory graafian follicles and their contents are seen to be key structures
      orchestrating the events of sperm progression and coordinating the subsequent
      meeting of male and female gametes. Three levels of control over the numbers of
      spermatozoa activated and released from the functional reservoir in the caudal
      region of the fallopian tube isthmus are proposed. A primary control would be
      obtained by means of a countercurrent transfer of ovarian follicular progesterone
      from the ovarian vein into the tubal branch of the ovarian artery. The
      concentration of progesterone so transferred would be proportional to the number
      of preovulatory follicles, and thus to the number of eggs to be shed, and would
      act progressively to reduce sperm binding to the endosalpinx of the caudal
      isthmus. Differential timing of the release from epithelial binding may be a
      crucial means of achieving the initial low sperm/egg ratios. a secondary
      regulation of the release of graded numbers of viable spermatozoa towards the
      ampullary-isthmic junction of the fallopian tubes would be by means of molecular
      messages derived from the mucified oocyte-cumulus complex shortly before and
      after the time of ovulation. Third would be reorientation of sperm trajectories
      by molecular gradients within the cumulus cell mass to direct competent
      spermatozoa to those oocytes as yet unpenetrated. Together these differing levels
      of control would impose low sperm/egg ratios during the initial stages of
      fertilisation, such strict quantitative regulation of male gametes lasting at
      least until the block to polyspermy is fully established and the vitellus is no
      longer at risk from further sperm penetration.

PMID- 8858612
TI  - Human cortical 40 Hz rhythm is closely related to EMG rhythmicity.
AB  - We recorded cortical neuromagnetic rhythms during self-paced index-finger
      movements from a subject previously reported to show prominent 40 Hz
      electroencephalographic activity during motor behavior. The 10 and 20 Hz
      components of the rolandic mu rhythm were bilaterally suppressed, whereas the
      contralateral 40 Hz (35-41 Hz) activity was slightly enhanced before both fast
      and slow movements and strongly enhanced during slow movements. The 40 Hz rhythm
      originated mainly in the hand motor cortex and was clearly correlated with the
      rhythmicity of the electromyogram from the extensor muscles, with a systematic
      time lag. In this subject motor preparation, and especially control of finger
      movements, may thus be associated with enhanced cortical rhythms near 40 Hz. The
      coherence of these rhythms with muscular firing patterns likely reflects
      communication between the sensorimotor cortex and the motor units.

PMID- 8858613
TI  - Administration of amyloid beta-peptides in the rat medial septum causes memory
      deficits: reversal by SR 57746A, a non-peptide neurotrophic compound.
AB  - Different putative toxic amyloid beta (A beta) peptides, beta (1-42), beta (1-40)
      and beta (25-35), were infused (0.75, 1.5 or 3 nmol) in the rat medial septum.
      Memory deficits were then investigated using the social recognition test. A
      significant amnesia was observed 4, 7 and 14 days after intraseptal injection of
      3 nmol of beta (1-42), beta-(1-40)- and beta (25-35). Lower amounts of beta (1
      42) were inactive except 1.5 nmol that disrupted memory 7 days post-treatment.
      Used as control, the inverted peptide beta (40-1) and the scrambled beta (25-35)
      were inactive. Using the prolongation procedure, rats infused with 3 nmol of beta
      (1-40) were still able to recognize the same juvenile. Finally, a daily treatment
      with the non-peptide neurotrophic compound SR 57746A (10 mg/kg p.o.) over 21
      days, prevented the deficits in short-term memory induced by the intraseptal
      infusion of 3 nmol of either beta (1-40) or beta (25-35). These findings suggest
      that A beta fragments could impair short-term memory when infused in the rat
      medial septum, an effect that is prevented by SR 57746A.

PMID- 8858614
TI  - Medium weight neurofilament mRNA in goldfish Mauthner axoplasm.
AB  - Although axons are generally considered to lack the ability to synthesize
      proteins, the Mauthner axon (M-axon) of the goldfish has been reported to contain
      some of the basic components of the translational machinery, such as transfer RNA
      (tRNA), ribosomal RNA (rRNA), and ribosomes. To determine if the M-axon also
      contains mRNA, we isolated samples of M-axoplasm free of glial contamination as
      demonstrated by the absence of glial-specific mRNA and protein. Reverse
      transcription-polymerase chain reaction (RT-PCR) of M-axoplasmic cDNA in the
      presence of primers for the goldfish medium-weight neurofilament (NF-M) gene
      produced a single product of the expected length for RT-PCR amplification of
      goldfish NF-M mRNA. This mRNA might direct protein synthesis of NF-M within the M
      axoplasm.

PMID- 8858616
TI  - Anti-GM3 (II3Neu5Ac-lactosylceramide) ganglioside antibody labels human fetal
      Purkinje neurons during the critical stage of cerebellar development.
AB  - The ganglioside GM3 (II3Neu5Ac-lactosylceramide) represents a minor ganglioside
      in normal human brain compared to major gangliosides with gangliotetraose
      backbone. In this study the presence of GM3 in three 23 and 24 weeks of gestation
      old human cerebella was demonstrated by immunostaining extracted gangliosides on
      thin-layer chromatography plate as well as by immunohistochemical analysis of
      cerebellar cryosections. During this stage of brain development GM3 was found to
      be dominantly expressed on cells corresponding to Purkinje neurons. Delipidation
      of histological sections with chloroform/methanol caused significant reduction of
      anti-GM3 immunostaining, thus confirming the prevalent ganglioside nature of this
      antigen. These results give evidence that (1) GM3 ganglioside is associated with
      a specific subset of human fetal cerebellar neurons during the critical
      development stage, and (2) a definite ganglioside in general is distributed to a
      specific subset of cells in normal human brain.

PMID- 8858615
TI  - Nervus terminalis projection to the retina in the 'four-eyed' fish, Anableps
      anableps.
AB  - The eye of the surface dwelling 'four-eyed' fish, Anableps possesses an aquatic
      and an aerial optical system. The aerial system is strongly hyperopic when the
      animal dives, i.e. during mating, and the dorsal pupil is submerged. We studied
      the retino-petal nervus terminals projection to the aerial and to the aquatic
      retina by Phe-Met-Arg-Phe-NH2 (FMRF) immunocytochemistry and found both to be
      equally innervated. This finding sheds doubt on the proposed functional
      significance of this projection for reproductive behaviour.

PMID- 8858617
TI  - Angiotensin II as a stimulator of Na(+)-dependent Ca2+ efflux from freshly
      isolated adult rat cardiomyocytes.
AB  - In cardiac tissues, angiotensin II causes inotropic and chronotropic effects on
      the heart. It is indicated that the mechanism of the inotropic effect of
      angiotensin II is attributed to an increase in cytosolic free calcium ([Ca2+]i)
      in cardiomyocytes. However, increased [Ca2+]i should be restored to a
      physiological level because cumulative elevation in [Ca2+]i leads to irreversible
      injury in cardiomyocytes. Whereas it is known that angiotensin II causes the
      increase in [Ca2+]i in cardiac cells, little is known about the mechanisms of
      decrease in [Ca2+]i in cardiomyocytes upon angiotensin II stimulation. In the
      present study, we examined the effect of angiotensin II on Ca2+ efflux from
      freshly isolated adult rat cardiomyocytes. Angiotensin II stimulated the efflux
      of 45Ca2+ from the cells in a concentration-dependent manner (10(-7)-10(-5) M).
      The 45Ca2+ efflux from the cells was inhibited by type 1 angiotensin II receptor
      inhibitor. The angiotensin II-stimulated 45Ca2+ efflux was not affected by
      deprivation of the extracellular Ca2+, but was dependent on the presence of
      extracellular Na+. These results indicate that angiotensin II stimulates
      extracellular Na(+)-dependent 45Ca2+ efflux from freshly isolated adult rat
      cardiomyocytes, probably through its stimulatory effect on the plasma membrane
      type 1 angiotensin II receptors which may couple to Na+/Ca2+ exchange.

PMID- 8858618
TI  - Relation of abnormal burst activity of spinal neurons to the recurrence of
      autotomy in rats.
AB  - Two groups of rats received different amounts of peripheral deafferentations; one
      group received sections of sciatic nerve (S-rats) and the other received sections
      of sciatic and saphenous nerves (SS-rats). In Experiment 1 the occurrence of
      autotomy was compared between S- and SS-rats for up to 70 days after the surgery.
      Autotomy in SS-rats frequently recurred until 40 days after denervation whereas
      in S-rats it scarcely recurred. In Experiment 2 spontaneous activity was recorded
      from the spinal cords in S- and SS-rats, and the proportion of burst firing cells
      (B-cells), characterized by periodic and high frequency bursts, was compared. In
      both S- and SS-rats with fresh wounds the occurrence of B-cells was high until 40
      days after denervation. However, B-cells were still frequently observed in SS
      rats with old wounds until 40 days after denervation, whereas B-cells were
      scarcely found in S-rats with similar old wounds. This finding corresponded well
      with the behavioral observation in Experiment 1. The data strongly suggests that
      the continuance of a high proportion of B-cells in the spinal cord plays an
      essential role for the induction of recurrent autotomy.

PMID- 8858619
TI  - Expression and localization of insulin-regulatable glucose transporter (GLUT4) in
      rat brain.
AB  - The localization of glucose transporters (GLUTs) was examined in various regions
      of the rat brain. The mRNA of GLUT1 and GLUT3 were found ubiquitously in every
      brain region (cortex, hippocampus, midbrain, striatum, hypothalamus, medulla
      oblongata and cerebellum). The mRNA and protein of GLUT4, an insulin-regulatable
      glucose transporter in peripheral tissues, were also identified, particularly
      abundantly in the cerebellum. In situ hybridization analysis revealed that GLUT4
      mRNA was present in some discrete cells, such as Purkinje cells in the
      cerebellum, the vestibular nucleus in the medulla oblongata and also in ependymal
      cells along the cerebral ventricles. The GLUT4 mRNA level in the cerebellum
      changed little in fasted or experimentally induced diabetic rats while those in
      adipose tissues decreased much. The results suggest that insulin-sensitive
      glucose uptake may occur in some specific cells of the brain but is regulated in
      a different manner from those in peripheral cells.

PMID- 8858620
TI  - Expression of dystrophin Dp71 during PC12 cell differentiation.
AB  - The expression of dystrophin-protein 71 (Dp71) was investigated during nerve
      growth factor (NGF) induced differentiation of PC12 cells. A semi-quantitative
      reverse transcription-polymerase chain reaction (RT-PCR) assay was designed to
      measure Dp71 mRNA, whereas the Dp71 protein amount was evaluated by immunoblot
      analysis using an anti-dystrophin monoclonal antibody. Comparison with control
      cultures showed that Dp71 mRNA and protein levels increased in parallel with NGF
      treatment peaking with increments of 60% and 1.4 times, respectively. The
      upregulation of Dp71 expression during PC12 cells differentiation point at PC12
      cells as a suitable model for studying the function of Dp71 in neuronal cells.

PMID- 8858622
TI  - Direct projections from the spinal cord to the trigeminal sympathetic ganglion of
      the puffer fish, Takifugu niphobles.
AB  - The sympathetic trunk of teleosts extends into the cranial levels, forming the
      cranial sympathetic ganglia. When horseradish peroxidase was applied to the
      trigeminal sympathetic ganglion (a sympathetic ganglion at the level of the
      trigeminal nerve) of the puffer fish, Takifugu niphobles, retrogradely labeled
      neurons were found in the central autonomic nucleus (a distinct cell column in
      the rostral part of the spinal cord). The central autonomic nucleus has been
      known to contain preganglionic neurons projecting to the sympathetic ganglia at
      the spinal levels. Thus, the present results indicate that the central autonomic
      nucleus in the spinal cord of teleosts contains not only preganglionic neurons
      projecting to the sympathetic ganglia at the spinal levels, but also neurons
      projecting to the sympathetic ganglia at the cranial levels.

PMID- 8858621
TI  - Ultrastructural morphological changes are not characteristic of apoptotic cell
      death following focal cerebral ischaemia in the rat.
AB  - We have used a permanent middle cerebral artery occlusion (MCAO) model in the rat
      to ascertain if the DNA fragmentation seen in nuclei, shows the characteristic
      ultrastructural features of apoptosis. Results from light and electron
      microscopic studies were compared with those from a neonatal model of excitotoxic
      cell death in which classical apoptotic changes were seen in a subpopulation of
      cells. At 6 and 24 h following occlusion, cells were either swollen or dark and
      shrunken showing a disordered cytosol. At 24 h survival a high number of cells in
      the lesion core and lesion border showed internucleosomal DNA breaks, which were
      detected in sections using terminal dUTP nick-end-labelling (TUNEL). Electron
      microscopy of cells with TUNEL positive spherical structures of condensed
      chromatin in the lesion core showed an advanced stage of cellular disintegration
      as opposed to an apoptotic morphology of a subpopulation of cells with chromatin
      condensation in the cortex and mammillary body of N-methyl-D-aspartate (NMDA)
      treated neonatal rats. We conclude that in focal cerebral ischaemia
      internucleosomal DNA fragmentation associated with chromatin condensation is a
      late consequence of ischaemic cell death rather than a hallmark of apoptosis.

PMID- 8858623
TI  - Selective induction of fibroblast growth factor receptor-1 mRNA after transient
      focal ischemia in the cerebral cortex of rats.
AB  - The expression of the mRNA of four members of the fibroblast growth factor (FGF)
      receptor family, was examined in rats subjected to temporal middle cerebral
      artery occlusion using an in situ hybridization technique. Fibroblast growth
      factor receptor-1 (FGFR-1) mRNA was strongly expressed in neurons of the cerebral
      cortex, whereas mRNAs of the other 3 subtypes of FGFRs (FGFR-2, -3, and -4) were
      not expressed. After temporal occlusion of the middle cerebral artery, expression
      of FGFR-1 mRNA in cerebral cortical neurons markedly increased in association
      with the progressive neuronal death; this increase was evident for at least 5
      days after the focal ischemia. In view of the neuroprotective activity of basic
      FGF reported so far, the present results suggest that FGFR-1 induction may
      subserve to self-protect neurons in the ischemic penumbral field of the cerebral
      cortex.

PMID- 8858624
TI  - Delayed progression of cytotoxic oedema in focal cerebral ischemia after
      treatment with a torasemide derivative: a diffusion-weighted magnetic resonance
      imaging study.
AB  - Diffusion-weighted magnetic resonance imaging (MRI) was used to assess the effect
      of an astrocytic Na+2Cl-K+ cotransporter inhibitor, a novel torasemide
      derivative, on the time course and spatial evolution of a focal cerebral ischemia
      in the rat. The drug (1 mg/ kg, i.p.) was injected 30 min before middle cerebral
      artery occlusion and diffusion-weighted images were acquired at various times
      thereafter. The results showed that the drug reduced the size of the
      hyperintensity during the first hours, but did not affect the time constant of
      growth or the final size. The temporary reduction of the cytotoxic oedema induced
      by the torasemide derivative, demonstrates an antioedematous activity.

PMID- 8858625
TI  - The caudo ventral pontine tegmentum is involved in the generation of high
      velocity eye saccades in bursts during paradoxical sleep in the cat.
AB  - Cat eye movements were recorded in the head restrained condition, with the
      technique of the scleral search coil in a magnetic field, and the maximum
      velocity/amplitude relationships were analyzed for saccades in the following
      conditions, (1) during waking (W); (2) during paradoxical sleep (PS); and (3)
      during W following carbachol microinjections in the medioventral part of the
      caudal pontine tegmentum. These findings indicate that (1) the neurophysiological
      mechanisms underlying carbachol induced events are similar to those acting during
      PS and that the caudal pontine tegmentum might be the generator of high velocity
      eye saccades in bursts accompanied by ponto geniculo occipital waves (PGOw)
      during PS, and (2) caudal pontine tegmentum neurons show 'state-dependent'
      responsiveness to cholinergic inputs, suggesting that a change in the synaptic
      inputs and/or the membrane properties of these neurons during PS may be
      responsible for the induction of saccadic eye movements in bursts and associated
      PGOw.

PMID- 8858626
TI  - Congenital hypothyroidism delays the formation and retards the growth of the
      mouse primary somatic sensory cortex (S1).
AB  - Intrinsic neural factors are thought to regulate the growth and formation of
      specific regions of the neocortex. To determine whether factors extrinsic to the
      brain are also involved in shaping the cytoarchitecture of the mammalian
      neocortex, we evaluated the effects of thyroid hormone (TH) on the formation and
      postnatal growth of the mouse S1 postero-medial barrel subfield (PMBSF).
      Congenital deficiency of TH, induced by propylthiouracil administration from day
      12 of gestation, did not disrupt S1 specification, because no alterations in
      barrel number or configuration were observed in congenital hypothyroid mice.
      Barrel formation, however, was delayed by 3 days. In control mice, barrels were
      first seen at postnatal day (PN) 4, whereas in congenital hypothyroid mice they
      appeared at PN7. TH deficiency led to reduced adult brain, cortical, and S1
      barrel dimensions. Barrel size, however, was relatively more affected than brain
      and cortical size. Our observations indicate, therefore, that TH does not
      participate in S1 specification, but in timing its formation. Our findings also
      indicate that TH regulates the relative size of the S1 barrel field by modulating
      the developmental timing of areal specification and brain growth.

PMID- 8858627
TI  - Chronic antipsychotic treatment alters glycine-stimulated NMDA receptor binding
      in rat brain.
AB  - In this study the chronic effect of antipsychotic drugs (APDs) on N-methyl-D
      aspartate (NMDA) receptor binding was evaluated. Rats were treated for 21 days
      with i.p. injections of haloperidol (0.5 mg/ kg), pimozide (0.5 mg/kg), clozapine
      (20 mg/kg), risperidone (1 mg/kg) or water vehicle (1 ml/kg). Brain tissue
      sections underwent different [3H]MK-801 assay conditions. Following a short
      preincubation wash, there were no effects of APDs on either unenhanced or agonist
      enhanced [3H]MK-801 binding. Following a prolonged preincubation wash, APDs
      resulted in a reduction in both unenhanced binding and glycine enhanced binding.
      The attenuation of glycine stimulation in the APD treated animals was selective
      as neither NMDA nor spermidine enhanced binding was significantly affected. The
      present data suggest specific actions at the glycine regulatory site on the NMDA
      receptor as part of the chronic effects of APDs.

PMID- 8858628
TI  - omega-agatoxin IVA and excitotoxicity in cortical neuronal cultures.
AB  - Because the P- and Q-type Ca2+ channel antagonist omega-agatoxin IVA inhibits
      glutamate release, agatoxin-related drugs could have a role in the treatment of
      excitotoxic neurologic disorders such as stroke. We examined the effect of omega
      agatoxin IVA on excitotoxicity (lactate dehydrogenase release) induced by
      depolarization with veratridine or ouabain, or by N-methyl-D-aspartate, in neuron
      enriched cerebral cortical cultures. omega-Agatoxin IVA (< or = 300 nM) failed to
      reduce excitotoxicity, as did the L-type Ca2+ channel antagonist nimodipine and
      the N-type antagonist omega-conotoxin GVIA. Drugs that inhibit glutamate release
      may not necessarily be neuroprotective.

PMID- 8858629
TI  - Nicotine rescues PC12 cells from death induced by nerve growth factor
      deprivation.
AB  - We examined the protective effect of nicotine against neuronal cell death in the
      model system of serum- and nerve growth factor (NGF)-free cultures of PC12 cells.
      Serum deprivation induced massive death of undifferentiated PC12 cells, which was
      inhibited by the addition of NGF, but not by the addition nicotine (100 microM).
      Even after PC12 cells had been differentiated by the treatment with NGF, serum
      and NGF deprivation induced rapid and massive death of these cells. The addition
      of nicotine (1-100 microM) to the deprivation system prevented such cell death
      almost completely. The protective effect of nicotine was abolished by
      hexamethonium or mecamylamine, inhibitors of nicotinic acetylcholine (nACh)
      receptors. Treatment with reserpine to deplete intracellular catecholamines did
      not influence the effect. The results suggest that the protective effect of
      nicotine against neuronal cell death is exerted through nACh receptors.

PMID- 8858630
TI  - Apraclonidine 0.5% versus 1% for controlling intraocular pressure elevation after
      argon laser trabeculoplasty.
AB  - BACKGROUND AND OBJECTIVE: Topical apraclonidine hydrochloride 1% is effective for
      controlling the intraocular pressure (IOP) rise following argon laser
      trabeculoplasty (ALT). The 0.5% formulation has recently become available
      commercially. The objective of this study was to compare the efficacy of these
      two concentrations for controlling IOP after ALT. PATIENTS AND METHODS: All
      patients undergoing ALT were prospectively randomized to receive either 1% or
      0.5% apraclonidine 1 hour before and immediately after the laser surgery. IOP was
      measured before and 2 and 24 hours after the treatment. RESULTS: No statistically
      significant difference in mean IOPs was found between the two treatment groups at
      any time. CONCLUSION: These data suggest that 0.5% and 1% apraclonidine are
      equally effective for preventing IOP rise after ALT.

PMID- 8858631
TI  - Subconjunctival versus intrascleral mitomycin-C in trabeculectomy.
AB  - BACKGROUND AND OBJECTIVE: A randomized prospective comparison of sub-Tenon's
      administration of mitomycin-C (MMC) with intrascleral administration of MMC in
      trabeculectomy was performed to determine whether intrascleral application is
      superior to the standard sub-Tenon's application. PATIENTS AND METHODS: Twenty
      four eyes of 23 patients were randomized to treatment with MMC (0.27 mg/ml for 5
      minutes). The route of administration was subconjunctival in group A and
      intrascleral in group B. Preoperative and postoperative visual acuity (VA),
      intraocular pressure (IOP), number of medications, and complications were
      compared between the two groups. RESULTS: There was no statistically significant
      difference between the two groups preoperatively regarding VA, IOP, and number of
      medications. Postoperatively, IOP and number of medications required had
      decreased significantly in both groups. A significantly larger number of
      postoperative procedures were required in group B to control IOP (group A = 3,
      group B = 14, P = .002). CONCLUSION: Both methods of MMC application
      significantly decreased the IOP and the number of medicines required to control
      IOP after trabeculectomy. The intrascleral use of MMC resulted in the need for
      more surgery postoperatively (P = .002).

PMID- 8858632
TI  - Indications for and complications of mitomycin-C in pterygium surgery.
AB  - BACKGROUND AND OBJECTIVE: The purposes of this study are to examine the
      complications and results of a novel approach to the use of mitomycin-C in
      pterygium surgery; to identify the lowest effective dosage required to prevent
      recurrence; and to select those high-risk pterygia that could benefit from
      mitomycin-C use. PATIENTS AND METHODS: One hundred thirty-five eyes of 128
      patients considered at high risk for recurrence of pterygium were treated with a
      single, intraoperative, subconjunctival injection of mitomycin-C at the site of
      excision. Three different dosages-0.2, 0.1, and 0.05 ml-at a strength of 0.5
      mg/ml were used. The eyes were observed for 10 months to 3 years. RESULTS: There
      were only two recurrences (1.5%); both occurred in eyes that had undergone
      previous pterygium surgery. One recurrence happened with the 0.2-ml dosage, and
      the other with the 0.1-ml dosage. These recurrences occurred in association with
      early wound dehiscence, which essentially became a bare sclera susceptible to
      pterygium regrowth. Complications included temporary and prolonged discomfort,
      tearing, hyperemia, subconjunctival hemorrhage, wound dehiscence, and pigment
      accumulation. No vision-threatening side effects were noted. CONCLUSIONS: The
      persistence and intensity of discomfort noted at the higher dosage has prompted
      these authors to suggest that only high-risk pterygia should receive mitomycin-C.
      Conjunctival flaps should always be used to cover the sclera up to the limbus and
      to localize the mitomycin-C to prevent its migration. A single dose of not more
      than 0.05 ml at a strength of 0.5 mg/ml subconjunctivally gives the same results
      as multiple drops, but with far less morbidity.

PMID- 8858633
TI  - Intraoperative mitomycin-C versus postoperative topical mitomycin-C drops for the
      treatment of pterygium.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of two different
      regimens of mitomycin-C (MMC) application as adjunctive chemotherapy in the
      treatment of pterygia. PATIENTS AND METHODS: One hundred fifty-six patients
      underwent pterygium excision using the bare sclera technique. They were randomly
      assigned to have either 0.1 mg/ml of MMC applied to the bare sclera for 3 minutes
      intraoperatively, or 0.05-mg/ml drops applied topically for 2 weeks
      postoperatively. The mean follow-up period was 11 months (range 7 to 17).
      RESULTS: Complications with the intraoperative MMC included 5 cases of recurrence
      (5.75%), 2 cases of superficial punctate keratitis (SPK), and 3 cases of delayed
      conjunctival wound healing. Topical MMC led to 6 cases of recurrence (6.9%), 5
      cases of SPK, 4 cases of delayed conjunctival wound healing, and 2 cases of mild
      iritis. CONCLUSION: A single, intraoperative application of MMC is a simple,
      effective alternative adjunctive treatment for pterygium.

PMID- 8858635
TI  - Cutaneous facial resurfacing with the carbon dioxide laser.

PMID- 8858634
TI  - Lacrimal bone thickness at the lacrimal sac fossa.
AB  - BACKGROUND AND OBJECTIVE: Because laser dacryocystorhinostomy techniques have
      become more popular during the past few years, interest has grown concerning the
      anatomic structures that need to be penetrated in these procedures. The authors
      therefore studied the thickness and the histologic type of the lacrimal bone at
      the lacrimal sac fossa. PATIENTS AND METHODS: The thickness of 69 lacrimal bones
      at the lacrimal sac fossa from 48 patients was measured. RESULTS: The mean
      thickness was 106 microns. In 67% of the patients the mean thickness of
      individual lacrimal bone was less than 100 microns and in 4% it was more than 300
      microns. The thinnest measured cross section of the lacrimal bone sample was 11
      microns and the thickest was 722 microns. The lacrimal bone was composed of a
      thin plate of lamellar bone. CONCLUSION: In most cases the lacrimal bone at the
      lacrimal sac fossa is so thin that it can be easily penetrated with most surgical
      instruments.

PMID- 8858636
TI  - Rhegmatogenous retinal detachments in HIV-positive patients with ocular syphilis.
AB  - The purpose of this study is to report retinal manifestations of lues in human
      immunodeficiency virus (HIV)-positive patients and to suggest a method for
      treatment of rhegmatogenous retinal detachments in these patients. Two HIV
      positive patients with bilateral retinitis were examined and treated at the
      authors' institution for a period of 14 months. Ocular syphilis was diagnosed
      clinically, confirmed by cerebrospinal fluid serologic testing, and treated with
      intravenous penicillin. Both patients experienced bilateral rhegmatogenous
      retinal detachments complicated by proliferative vitreoretinopathy after
      resolution of the active retinitis. All four eyes underwent surgical repair with
      trans pars plana vitrectomy, epiretinal membrane delamination, gas-fluid
      exchange, endolaser, scleral buckle, and silicone oil instillation. The
      recognition of ocular syphilis as a cause of retinal detachment in HIV-positive
      patients is important. Prompt intervention with the appropriate medical and
      surgical treatments may result in the preservation of vision in these patients.

PMID- 8858637
TI  - Intraconal amphotericin B for the treatment of rhino-orbital mucormycosis.
AB  - Rhino-orbital-cerebral mucormycosis is a disease that is frequently fatal. A 39
      year-old man with diabetic ketoacidosis was referred to the authors' ophthalmic
      service with fever, orbital apex syndrome in the right eye, lethargy, and a black
      eschar in the palate. He was treated with systemic and local (intraconal)
      amphotericin B and his ketoacidosis was controlled; exenteration was not
      performed. Biopsy of the palate proved mucormycosis. Eighteen months later the
      patient was still alive and had a blind, anatomically preserved right eye with
      ptosis and intact extraocular muscle function without proptosis or pain. The
      authors propose this alternative means of treatment to achieve higher doses of
      the drug at the site of infection and better cosmetic and psychological results.

PMID- 8858638
TI  - Regression of rubeosis iridis after trabeculectomy combined with mitomycin-C.
AB  - The authors report two cases in which severe rubeosis iridis regressed after
      trabeculectomy with intraoperative application of mitomycin-C. Several days after
      the operation, the vessels were no longer perfused. Only white, empty, "ghost"
      vessels were visible. This phenomenon was observed in one case with well
      controlled intraocular pressure (IOP) after surgery, as well as in a case in
      which IOP rose again to high preoperative values. The authors conclude that the
      regression of the rubeosis may be caused by a local, intraocular pharmacologic
      side effect of mitomycin-C, not by the drop in IOP alone.

PMID- 8858639
TI  - Lipogranuloma: a preventable complication of dacryocystorhinostomy.
AB  - This report describes the unusual occurrence of lipogranuloma at the incision
      site of dacryocys-torhinostomy. Four patients had soft cystic masses after
      external dacryocystorhinostomy for acquired nasolacrimal duct obstruction. This
      was attributed to the antibiotic ointment vehicle that coated the petroleum jelly
      impregnated gauze placed intranasally to prevent epistaxis. Postoperatively, all
      four patients had an encapsulated cystic mass within 3 weeks. Three of the masses
      were excised under local anesthesia and one was aspirated. None of the masses
      recurred.

PMID- 8858640
TI  - Thelazia californiensis conjunctival infestation.
AB  - There are few reports of Thelazia californiensis infestation in humans in the
      literature. The authors report the clinical and histopathologic features of two
      patients who presented with symptoms of a mild unilateral chronic conjunctivitis
      from infestation by this parasite. In each case, the symptoms resolved
      immediately after removal of the worms. These are the first two patients from the
      Rocky Mountain area to be described with an infection from this particular worm.
      T. californiensis should be included in the differential diagnosis of patients
      with chronic conjunctivitis following hiking or camping in the mountains or back
      country.

PMID- 8858641
TI  - Use of a mirror needle holder with transsclerally sutured posterior chamber
      intraocular lenses.
AB  - A mirror needle holder has been designed to facilitate the passage of a needle
      through the ciliary sulcus during transscleral fixation of posterior chamber (PC)
      intraocular lens (IOLs). Two human postmortem eyes were used to demonstrate the
      efficacy of this mirror used as the needle holder. This method was compared with
      the current method of passing sutures without view of the ciliary sulcus. The
      mirror needle holder demonstrated precise passage of the needle into the ciliary
      sulcus by direct visualization of the ciliary processes and sulcus. This method
      may avoid the complications associated with transsclerally sutured PC IOLs during
      penetrating keratoplasty and secondary IOL placement.

PMID- 8858642
TI  - An ophthalmic drape with a built-in breathing outlet.
AB  - An ophthalmic surgical drape with an ancillary breathing outlet is described and
      illustrated. It is believed that this drape will supply a needed emergency
      feature in current ophthalmic surgical drapes that will contribute to greater
      safety among elderly patients and give greater assurance to the surgeon who may
      experience a sudden interruption in surgery caused by an unexpected respiratory
      problem.

PMID- 8858644
TI  - Initial end-tidal CO2 is markedly elevated during cardiopulmonary resuscitation
      after asphyxial cardiac arrest.
AB  - OBJECTIVES: To compare the initial end-tidal CO2 (PetCO2) during cardiopulmonary
      resuscitation in asphyxial versus ventricular fibrillatory cardiac arrest.
      DESIGN: A cohort study. SETTING: University research laboratory. SUBJECTS: Forty
      domestic piglets. INTERVENTIONS: Asphyxial cardiac arrest was produced by
      clamping the endotracheal tube in 20 piglets and was continued for 10 minutes
      after loss of aortic pulsations occurred. Ventricular fibrillation (VF) was
      induced by applying 60 Hz of alternating current via a pacing wire to the
      myocardium of the other 20 piglets, and continued for a 15-minute downtime.
      Cardiopulmonary resuscitation (CPR) was then provided to each group for two
      minutes, followed by standard advanced cardiac life support protocols.
      MEASUREMENTS AND MAIN RESULTS: All piglets were instrumented for continuous
      monitoring of PetCO2, electrocardiogram, central venous pressure, and aortic
      pressure. PetCO2 of the first breath of CPR was 91 +/- 20 mmHg in the asphyxial
      group versus 34 +/- 14 mmHg in the VF group (P < 0.001). The asphyxial group
      continued to exhibit significantly greater PetCO2 for the first five breaths of
      resuscitation, after which there were no differences. The coronary perfusion
      pressures during the first breaths of CPR did not differ between the two groups.
      High initial PetCO2 did not correlate with return of spontaneous circulation.
      CONCLUSIONS: End-tidal CO2 during the first five breaths of CPR is much higher
      after an asphyxial cardiac arrest than VF. In each case, the initial PetCO2
      appears to reflect alveolar CO2 prior to CPR. After one minute of CPR, PetCO2 is
      useful in monitoring the effectiveness of CPR.

PMID- 8858643
TI  - Soy allergy and DSCG in atopic eczema: "much ado about nothing"?

PMID- 8858645
TI  - Alterations of end-tidal carbon dioxide during the intrahospital transport of
      children.
AB  - OBJECTIVE: To determine the effect of manual ventilation during intrahospital
      transport on end-tidal carbon dioxide concentrations in children. DESIGN:
      Prospective study in children who required tracheal intubation and mechanical
      ventilation/ hyperventilation to maintain an arterial partial pressure of CO2
      (PaCO2) of 25 to 30 torr for control of intracranial pressure. SETTING: Pediatric
      intensive care unit. INTERVENTION: During patient transport with manual
      ventilation, end-tidal CO2 was monitored with a side-streaming aspirating,
      infrared device. The person responsible for manual ventilation was informed of
      the current ventilator settings and the need to maintain a PaCO2 of 25 to 30
      torr, but was not allowed to see the end-tidal CO2 monitor. RESULTS: The study
      population included 12 patients ranging in age from seven months to 14 years
      (average age 6.9 years) and in weight from 6.5 to 57 kg (average weight 28.9 kg).
      A total of 1716 end-tidal CO2 values were recorded during 286 minutes of
      monitoring. Five hundred and thirty-one (31%) of the readings were in the
      intended range of 25 to 30 torr. Four hundred (23%) were less than 20 torr, 665
      (39%) were in the 20 to 24 torr range, and 119 (6.3%) were greater than 30 torr.
      Only five were greater than 40 torr. CONCLUSIONS: Unintentional hyperventilation
      occurs during the intrahospital transport of children. End-tidal CO2 values less
      than 25 torr were noted 62% of the time.

PMID- 8858646
TI  - Noninvasive capnometry in a pediatric population with respiratory emergencies.
AB  - OBJECTIVE: This study was designed to investigate the reliability, safety, and
      efficacy of measuring end tidal CO2 (ETCO2) in nonintubated pediatric patients
      presenting to an emergency department (ED) with respiratory emergencies.
      DESIGN/SETTING/PATIENTS: Eighty-five children were enrolled in a clinical,
      prospective, observational study at a university-affiliated children's hospital.
      Children age four weeks to 15.3 years with upper and lower respiratory diseases
      were enrolled by convenience sampling over a five-month period. INTERVENTIONS:
      ETCO2 measurements were obtained on each patient by oral/nasal side-stream
      capnometry. When a consistent waveform was obtained, the value was compared with
      a capillary arterial partial pressure of CO2 (CapCO2), oxygen saturation (O2Sat),
      and clinical observations. RESULTS: Study patients had a mean ETCO2 reading of 33
      mmHg with a standard deviation (SD) of 4.6 mmHg and CapCO2 reading of 36 mmHg
      with a SD of 4.5 mmHg. Pulmonary findings, final diagnosis, and age did not
      significantly alter the relationship between CapCO2 and ETCO2. The relationship
      between CapCO2 and ETCO2 was significant (t = 14.9, P < 0.0001, r = 0.87), with a
      95% confidence interval for prediction of +/-5 mmHg. CONCLUSION: Dependable ETCO2
      values can be obtained using an oral/nasal capnometry circuit, and they
      consistently correlate with CapCO2 in a pediatric population with upper and lower
      respiratory diseases. Noninvasive ETCO2 analysis is safe and reliable within the
      limitations of this study group. Further exploration is necessary to determine
      the value of this technology in assisting with clinical decisions in the patient
      with impending respiratory failure.

PMID- 8858647
TI  - Prediction of childhood drowning and near-drowning morbidity and mortality.
AB  - OBJECTIVES: (a) Evaluate the presenting hemodynamic status and neurologic
      function of a series of warm water submersion injuries. (b) To ascertain the
      importance of the timing of the neurologic examination. (c) To identify risk
      factors that predict which patients will not return to presubmersion status.
      DESIGN: Retrospective review of all patients with a diagnosis of drowning/near
      drowning responded to by the Children's Hospital pediatric transport service.
      Data were collected over a 24-month period regarding patient characteristics,
      submersion medium, rescue efforts, time out of sight, elapsed times to emergency
      department (ED) and pediatric intensive care unit (PICU) arrival, neurologic and
      hemodynamic status on arrival at the ED and PICU, reconstructed Conn-Modell
      category, and neurologic outcome. SETTING: EDs of the referring hospitals and
      PICU of the Children's Hospital of Orange County (CHOC), California. PATIENTS:
      Ninety-three submersion victims at an average age of 31 months. All patients were
      provided intensive care support. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Twenty-three percent (21/ 93) of patients died or survived vegetative.
      No patient arriving comatose and asystolic in the ED survived neurologically
      intact (n = 21, three patients expired in the ED). This group of patients had a
      mean duration of documented asystole = 41 minutes, range of 18 to 107 minutes,
      and time to ED arrival = 21 minutes. All patients with a detectable pulse and
      blood pressure (n = 72) on arrival to the ED, regardless of their neurologic
      status, recovered to their presubmersion status. Patients arriving comatose
      (decorticate, decerebrate, or flaccid posture) in the PICU (n = 18, mean arrival
      = 192 minutes) all died or were vegetative. All patients with non-coma (n = 72,
      Conn-Modell category A or B) on arrival to the PICU recovered normally.
      CONCLUSIONS: Hemodynamic status in the ED and neurologic status in the PICU are
      highly predictive of outcome. On arrival to the ED, the cardiovascular status is
      more predictive of abnormal outcome than neurologic status. Poor neurologic
      outcome appears inevitable for warm water submersion victims who are asystolic at
      ED arrival and remain comatose for more than 200 minutes.

PMID- 8858648
TI  - In-line skate and rollerskate injuries in childhood.
AB  - OBJECTIVE: To describe the estimated frequency and types of injuries associated
      with in-line skates in U.S. children and to compare in-line skating injuries to
      rollerskating injuries. DESIGN: National case series. SETTING: Emergency
      departments of hospitals participating in the United States Consumer Product
      Safety Commission (USCPSC) National Electronic Injury Surveillance System.
      PATIENTS: Persons with injuries associated with the use of in-line skates or
      rollerskates reported to the USCPSC in 1992 and 1993. RESULTS: There were an
      estimated 66,465 injuries associated with in-line skates; the incidence of injury
      was highest in children 11 and 12 years old. An estimated 40,730 in-line skate
      injuries involved children < 20 years old. The mean age of injured children was
      11.8 years (median, 12 years); 68% were boys. Fractures (45%) were the most
      common injury; 66% of fractures involved the distal forearm. Five percent had
      head injuries. Two and one half percent required hospital admission; 90% of
      children admitted had a fracture and 11% had a head or face injury. There were an
      estimated 147,928 rollerskating injuries among children < 20 years old; the mean
      age was 10.5 years (median 10 years) (P < 0.001 vs in-line skates). Thirty-two
      percent were to boys (P < 0.001 vs in-line skates). Fractures were the most
      common injury; forearm fractures accounted for 72% (P < 0.001 vs in-line skates).
      Five percent had head injuries. One and one half percent were admitted to the
      hospital (P < 0.001 vs in-line skates). In 1993, the injury rate among children
      for in-line skates was 31/100,000, and the injury rate for rollerskates was
      95/100,000. CONCLUSIONS: Injuries associated with in-line skates are highest
      among preadolescents. Injuries associated with in-line skate use are less common
      than injuries associated with rollerskate use. Distal forearm fractures are the
      most common injuries related to both in-line skate and rollerskate use. Exposure
      data and analysis of the efficacy of protective gear, including wrist guards and
      helmets, are needed.

PMID- 8858649
TI  - Delivery of albuterol in a pediatric emergency department.
AB  - STUDY OBJECTIVE: To determine if albuterol delivery by the combination of a
      metered-dose inhaler (MDI) with a spacer is equal in effectiveness to
      nebulization in a pediatric emergency department setting. DESIGN: Prospective
      series. SETTING: Urban children's hospital emergency department. PARTICIPANTS:
      Patients > or = six years of age with the diagnosis of acute asthma exacerbation.
      Exclusion criteria consisted of impending respiratory failure and corticosteroid
      administration within the preceding seven days. INTERVENTIONS: Patients were
      randomized into either the nebulizer treatment group or one of two MDI-spacer
      treatment groups (two spacers were evaluated). Each patient received three
      albuterol treatments administered evenly over one hour. The dose ratio for
      albuterol by nebulizer versus MDI-spacer was 6.9:1. Outcome was assessed by
      comparing the pre- and posttreatment percent predicted respiratory rate and
      percent predicted peak expiratory flow rate (PEFR) for each patient. RESULTS:
      Sixty patients were enrolled in the study. All three treatment groups showed
      significant improvement following albuterol therapy in both percent predicted
      respiratory rate and percent predicted PEFR. When comparing the three groups
      against each other in regard to outcome, no significant differences were found in
      improvement of percent predicted respiratory rate (P = 0.3258) or percent
      predicted PEFR (P = 0.9362). CONCLUSION: In a pediatric emergency department
      setting, aerosolized albuterol delivered by MDI-spacer was equal in effectiveness
      to nebulization in the acute asthma management of children > or = six years of
      age.

PMID- 8858650
TI  - Family member presence during pediatric emergency department procedures.
AB  - OBJECTIVE: Exclusion of family members (FM) during pediatric procedures in the
      emergency department (ED) is an accepted practice. This study questions the
      validity of such a practice. SUBJECTS: FM of ED pediatric patients undergoing
      procedures and ED staff performing procedures. SITES: ED of a tertiary care
      university-affiliated community hospital and the pediatric ED of a university
      hospital. METHODS: Post-procedure surveys were obtained from FM remaining with
      their child during an ED procedure and from the ED personnel performing the
      procedures. FM activity during the procedure was also recorded. RESULTS: Ninety
      six children (average age 20 months) underwent a total of 127 procedures. ED
      procedures included: vascular access 91, lumbar puncture 23, urethral
      catheterization 9, nasogastric tube placement 1, rapid sequence intubation 1,
      fluid resuscitation from shock 1, and removal of foreign body from eye 1. Three
      children were critically ill during performance of procedures. ED staff answered
      98 surveys concerning the performance of the 127 procedures. FM ACTIVITIES
      INCLUDED: Stood at bedside 35 (31%), soothed child 21 (19%), and helped restrain
      child 55 (55%). In 55 (57%) cases the FM was the only adult present with the ED
      staff member performing the procedure(s). FM MEMBER OPINIONS OF PRESENCE DURING
      PROCEDURES WERE: Good idea 101 (91%), bad idea 6 (5%), and did not care 4 (4%).
      ED staff opinions were: good idea 92 (93%), bad idea 2 (2%), and did not care 4
      (5%). FM presence made four (5%) members of the ED staff nervous. CONCLUSION: FM
      presence during ED procedures is a practice favored by both parents and ED staff
      at our institutions. This practice should not be limited to minimally invasive
      procedures in stable patients but should be considered for procedures such as
      lumbar punctures and intubations even in critically ill patients.

PMID- 8858651
TI  - The evaluation of pediatric trauma care using audit filters.
AB  - OBJECTIVE: To evaluate the experience of a pediatric trauma system with specific
      reference to prehospital, trauma center resuscitation, and critical care phases
      of treatment. DESIGN: Descriptive review of concurrent audit. SETTING: A tertiary
      care referral adult and pediatric trauma center. PATIENTS: All pediatric trauma
      victims in the trauma registry (includes patients < or = 14 years old, who died
      or were hospitalized for > or = 24 hours). INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Age, pediatric trauma, injury severity, and Glasgow Coma Scale
      scores as well as outcome (death or discharge disability score) were analyzed.
      Primary filters (those with the potential to contribute to morbidity and
      mortality), secondary filters (minor deviations from care), missed injuries and
      all deaths were reviewed. Of 250 patients in the registry, 20 died. One hundred
      thirteen had filters, with 49 having primary filters (34 with one, 14 with two,
      and one with four filters). Fifty percent of primary filters occurred in the
      prehospital phase of care with inadequate airway management and venous access
      accounting for 60%. Overall, primary filters occurred more commonly in patients
      with severe injuries (lower Pediatric Trauma and Glasgow Coma Scale and higher
      Injury Severity scores). Primary filters were also statistically more common in
      patients who died or who were disabled. In three patients (25%) who died, our
      review suggested that filters may have contributed to demise. Missed injuries
      were mostly extremity fractures and did not contribute to mortality or long-term
      morbidity. CONCLUSION: Deviations from care occur, even in a dedicated pediatric
      trauma system. Mortality of and by itself is not an adequate indicator of the
      quality of function of a trauma system. Since most primary filters occurred
      outside of the trauma center, improvement in trauma outcome may be expected with
      better training of personnel involved in the prehospital care of injured
      children. A comprehensive review of death and disability should include audit
      filters of prehospital care, triage, definitive care, and rehabilitation.

PMID- 8858652
TI  - Regional variation of nonrural pediatric ambulance transport rates: an ecological
      study.
AB  - STUDY OBJECTIVE: To determine the relationship of pediatric transport rates per
      hundred thousand pediatric population (RATE) to socioeconomic status (SES)
      factors and also mortality in Emergency Medical Services (EMS) systems. DESIGN:
      Retrospective ecological study. SETTING: Four EMS Medical Control Authorities
      (MCAs) in Michigan. PARTICIPANTS: Patients (3,792), 0-19 years of age, responded
      to as a nonscheduled emergency response and transported to a hospital by
      ambulance. METHODS AND MEASUREMENTS: RATE, economic status (INCOME), private
      transportation status (VEHICLE), educational status (EDUC), primary care
      physician availability (PHYS), and EMS disease death rate (EMSDD) were determined
      for each MCA and analyzed using Spearman rank correlation. RESULTS: RATE between
      MCAs varied from 325 to 750. RATE was highest in the most urban MCA: its 0-4 RATE
      was fourfold larger than any other MCA. INCOME, EDUC, and VEHICLE were inversely
      correlated with transport rate: -1.00, -1.00, -1.00; P < 0.001. Rate was
      positively correlated with EMSDD: 1.00; P < 0.001. CONCLUSIONS: Substantial
      variation in RATE between MCAs may be primarily due to the high 0-4 transport
      rate in the most urban MCA. This study also suggests that higher pediatric EMS
      system utilization rates may be correlated to higher mortality and also to
      unavailability of personal transportation.

PMID- 8858653
TI  - Nonaccidental injury presenting as pneumococcal sepsis in an infant.

PMID- 8858654
TI  - An uncommon presentation of Salmonella.
AB  - Salmonella infection can cause appendicitis by direct invasion of the appendix,
      or can mimic appendicitis by causing mild inflammation of the appendix, ileum, or
      lymph nodes. Clinical presentation and radiologic and laboratory evaluation may
      not distinguish the extent of underlying pathology. This case of a child with an
      atypical presentation of Salmonella who underwent diagnostic laparotomy
      illustrates the overlap of enteric infections and acute appendicitis. A
      literature review confirms the variety of clinical scenarios of patients with
      suspected appendicitis and Salmonella-positive cultures. We conclude that enteric
      infection should be considered in children with atypical presentations of
      appendicitis, and that the knowledge that Salmonella can progress to appendicitis
      should guide management if signs and symptoms of appendicitis develop.

PMID- 8858655
TI  - Staphylococcal tracheitis, pneumonia, and adult respiratory distress syndrome.
AB  - A child initially seen in the emergency department with respiratory distress was
      diagnosed with viral laryngotracheitis and discharged home on oral steroids. She
      returned the following day without abatement of her symptoms and was admitted
      with upper airway obstruction and pneumonia. Bacterial tracheitis was diagnosed
      when the tracheal aspirate grew a pure culture of Staphylococcus aureus.
      Hemodynamic instability and severe parenchymal lung disease ensued from septic
      shock and adult respiratory distress syndrome requiring inotropic support and
      assisted ventilation. Oscillatory ventilation was instituted when the patient
      failed conventional ventilation.

PMID- 8858656
TI  - Acute hepatic failure related to chronic acetaminophen intoxication.

PMID- 8858657
TI  - Continuous ketamine infusion for the treatment of refractory asthma in a
      mechanically ventilated infant: case report and review of the pediatric
      literature.

PMID- 8858658
TI  - Unusual cause of seizure.
AB  - INTRODUCTION: This case report of camphor ingestion in a 15-month-old child
      illustrates the potential toxicity of a common household product. Details of the
      patient presentation are reported along with a review of the literature. METHODS:
      Patient information was collected using the records of Poison Control, the
      Emergency Department, and the Health Records at the Hospital for Sick Children in
      Toronto, Ontario, Canada. A comprehensive review of the literature was conducted
      using the MEDLINE database for the time period 1966 to April 1995. DISCUSSION:
      Oral ingestion of camphor is unusual, given that these products have both
      unpleasant taste and texture. This patient ingested 70 ml of an over-the-counter
      medicated ointment containing 4.73% camphor, 2.6% menthol, and 1.2% eucalyptus
      oil. While the concentration of camphor in this product is low, an estimated 280
      mg/kg of camphor was consumed. With significant ingestion of camphor (> 50
      mg/kg), neurologic toxicity is common. In this patient, prolonged generalized
      tonic-clonic seizure activity was noted approximately two hours post single acute
      ingestion of camphor. This delay in onset of seizure activity is atypical, as
      seizures have previously been noted to occur in the 90 minutes following
      ingestion. CONCLUSION: Readily available medicated ointments containing camphor
      have potential for serious or fatal consequences when ingested by children.

PMID- 8858659
TI  - The ED on line: computerization of the pediatric emergency department.
AB  - Computers are becoming an increasingly important tool in the management of
      emergency departments across the United States. Many emergency physicians are
      unfamiliar with computer systems and are uncomfortable with the idea of
      implementing computer technology into their departments. This article summarizes
      the benefits of computerized patient tracking systems and outlines the process by
      which such a program can be selected and incorporated into an emergency center.

PMID- 8858660
TI  - Motor vehicle accident: closed head injury.

PMID- 8858661
TI  - Pediatric emergency medicine: legal briefs.

PMID- 8858662
TI  - Consultant's role.

PMID- 8858664
TI  - Sepsis, septic shock, acute abdomen? The ability of cardiac disease to mimic
      other medical illness.
AB  - Transport medicine offers the challenge of patient diagnosis based only on the
      relayed history an the impressions of referring medical personnel. A thorough
      pretransport review of the patient's history, physical examination, radiographs,
      laboratory values, and other supporting information can help avoid surprises upon
      arrival at the patient's bedside and lead to an appropriate diagnosis and
      management plan. One must approach the transported child with an open mind,
      however, to avoid misdiagnosis and inadequate or inappropriate intervention and
      management. One of the advantages of pediatric specialty transport services is
      the ability to critically assess a referred patient and offer diagnostic and
      therapeutic guidance in addition to transportation to the receiving center. These
      above two examples illustrate difficult cases where the diagnostic skills of the
      transport medical personnel enabled the patients to receive appropriate acute
      interventional and specific disease-related therapy.

PMID- 8858665
TI  - The future of polio immunization in the United States: are we ready for change?

PMID- 8858667
TI  - Large outbreak of pertussis among young children in Chicago, 1993: investigation
      of potential contributing factors and estimation of vaccine effectiveness.
AB  - BACKGROUND: An outbreak of pertussis from July, 1993, to April, 1994, in Chicago
      was investigated to identify potential contributing factors. METHODS:
      Surveillance was enhanced to identify cases. Information from a vaccination
      coverage survey was used to define a retrospective cohort to estimate vaccine
      effectiveness of three or more doses of pertussis vaccine. RESULTS: The median
      age of 218 reported cases was 8 months, 46% had Hispanic surnames and cases were
      clustered geographically. Vaccination status was known for 173 of 191 (91%)
      children younger than 6 years of age. Of these 173, 90 (52%) were younger than 7
      months, and 35 (20%) children at least 7 months of age had received fewer than 3
      doses of pertussis vaccine. Pertussis vaccine effectiveness was 76% (95%
      confidence interval, 29 to 92). CONCLUSIONS: The limited ability of the current
      pertussis vaccination schedule to protect young infants accounted for 52% of
      cases, primary vaccine failure accounted for 28% of cases and failure to
      vaccinate children on time accounted for 20% of cases in young children. Low
      vaccine effectiveness did not appear to be a contributing factor.

PMID- 8858666
TI  - Evaluation of a live attenuated bovine parainfluenza type 3 vaccine in two- to
      six-month-old infants.
AB  - BACKGROUND: A safe and effective parainfluenza type 3 (PIV-3) virus vaccine is
      needed to prevent serious PIV-3-associated illness in infants younger than 6
      months of age. In previous studies a live bovine PIV-3 (BPIV-3) vaccine, which
      was developed to prevent human PIV-3 (HPIV-3) disease, was shown to be safe,
      infectious, immunogenic and phenotypically stable in 6- to 36-month-old infants
      and children. METHODS: The safety, infectivity and immunogenicity of a single
      dose of the BPIV-3 vaccine was evaluated in a randomized, placebo-controlled,
      double blinded trial in 19 infants 2 to 5.9 months of age and in 11 additional 6-
      to 36-month-old subjects. RESULTS: The BPIV-3 vaccine was well-tolerated in both
      age groups and infected 92% of those younger than 6 months and 89% of those older
      than 6 months of age. Serum hemagglutination-inhibition (HAI) antibody responses
      to HPIV-3 and to BPIV-3, respectively, were detected in 42 and 67% of the younger
      infants, compared with 70 and 85% of the older subjects. In the younger infants
      we analyzed the rate of antibody response by titer of maternally acquired
      antibodies; low titer was defined as a preimmunization serum HAI titer < 1:8 and
      high titer was defined as a preimmunization serum HAI titer > or = 1:8. Young
      infants with a low titer of maternally acquired antibodies were significantly
      more likely to respond to the BPIV-3 vaccine that those with a high titer (89%
      vs. none for serum HAI response to BPIV-3; P = 0.02, Fisher's exact test).
      CONCLUSIONS: This study demonstrated that the BPIV-3 vaccine was safe and
      infectious in infants younger than 6 months of age and was also immunogenic in
      the majority of these young infants. Additional studies are needed to determine
      whether two or more doses will enhance the immunogenicity of the BPIV-3 vaccine
      in young infants and to assess its safety and immunogenicity when given
      simultaneously with routine childhood immunizations.

PMID- 8858668
TI  - Acceptability and usefulness of vaginal washes in premenarcheal girls as a
      diagnostic procedure for sexually transmitted diseases. The Child Protection
      Centre at the Winnipeg Children's Hospital.
AB  - OBJECTIVE: To assess the suitability of vaginal washes as specimens for sexually
      transmitted disease diagnosis and determine the usefulness of PCR technology for
      Chlamydia trachomatis diagnosis in prepubertal girls. STUDY DESIGN: Paired sets
      of vaginal secretions were collected with swabs and by vaginal wash from 138
      prepubertal girls for evaluation because of alleged sexual abuse. Detection by
      culture of Neisseria gonorrhoeae and C. trachomatis was compared between the two
      sampling techniques. PCR techniques were also used to test 29 vaginal wash
      specimens for C. trachomatis. RESULTS: In the prepubertal girls N. gonorrhoeae
      was detected in two wash specimens but in only one swab specimen; C. trachomatis
      was detected by culture in both paired specimens from two children and by PCR in
      vaginal washes from both of the two children positive by culture; PCR identified
      two other infected children. CONCLUSIONS: A vaginal wash technique coupled with
      newer molecular amplification technology may be useful in the assessment of
      sexually abused children.

PMID- 8858669
TI  - Colonization with penicillin-nonsusceptible Streptococcus pneumoniae in urban and
      rural child-care centers.
AB  - OBJECTIVES: To determine the prevalence of penicillin-nonsusceptible
      Streptococcus pneumoniae (NS-SP) at 12 child-care centers (CCC) in urban and
      rural Nebraska and to evaluate the genetic diversity of pneumococcal strains
      present in the CCC environment. METHODS: Nasopharyngeal cultures for S.
      pneumoniae were obtained from children 2 to 24 months old. Capsular serotyping,
      pulsed field gel electrophoresis (PFGE) and microbroth dilution MICs were
      performed for all S. pneumoniae. Antibiotic exposure was also evaluated as a
      potential risk factor for colonization with NS-SP. RESULTS: Nasopharyngeal
      colonization with S. pneumoniae was present in 121 (56%) of 215 children. The
      MICs of penicillin were 0.12 to 1.0 microgram/ml for 57 (47%) and > 1.0
      microgram/ml for 10 (8%) isolates. Clindamycin MICs of > 0.5 microgram/ml were
      found in 6 isolates (5%). MICs of ceftriaxone were 0.5 microgram/ml in 28% of S.
      pneumoniae and 1.0 microgram/ml in 7%. PFGE and capsular serotyping demonstrated
      multiple strains that were penicillin-nonsusceptible in both the urban and rural
      CCC. PFGE and capsular serotype defined shared strains within each CCC, but some
      PFGE "types" could be found in multiple serotypes. Antibiotic exposure during the
      2 months before nasopharyngeal culture was not a statistically significant risk
      factor for nasopharyngeal colonization with NS-SP. CONCLUSIONS: NS-SP are highly
      prevalent in urban and rural Nebraska. PFGE similarities between serotypes may
      reflect "serotype switching" but may also reflect genetic similarity between S.
      pneumoniae strains.

PMID- 8858670
TI  - Neonatal rotavirus infection in Bangladesh: strain characterization and risk
      factors for nosocomial infection.
AB  - BACKGROUND: Rotavirus (RV) diarrhea is an important cause of childhood morbidity
      and mortality in Bangladesh and is responsible for 24% of hospital admissions for
      diarrhea in children from 3 months to 2 years of age. However, the prevalence of
      neonatal RV infections and characteristics of RV strains infecting neonates have
      not been explored in Bangladesh. METHODS: We investigated neonates at six
      hospitals in Bangladesh to determine the prevalence of neonatal RV infection, to
      identify risk factors for infection and to characterize neonatal RV strains by
      reverse transcription-polymerase chain reaction. RESULTS: Of 381 neonates
      screened at 6 hospitals 61 of 146 infants (42%) at 2 hospitals in Dhaka were RV
      positive. Of these 62% were detected within the first 5 days of life. We found an
      increased risk for neonatal RV infection among infants whose mothers reported no
      handwashing during care of the neonate (P = 0.03). Analysis of RV strains in
      enzyme-linked immunosorbent assay-positive specimens identified P[6]G4 and P[6]G1
      genotypes to be most common; 7% (2 of 27) of strains were nontypable. A
      concurrent analysis of RV strains circulating in Bangladesh suggested that RV
      genotypes infecting neonates had a distinct P genotype, because most community
      strains were P-nontypable compared with neonatal strains, which carried the P[6]
      genotype. CONCLUSIONS: Hospitalized neonates in Dhaka have increased risk for
      infection with RV as early as the first week of life with strains having the
      unusual P[6] genotype. Our findings confirm studies in India showing that
      neonatal RV infection can be common and may occur with strains distinct from
      those circulating in the community. Neonatal RV infections could alter a child's
      response to the RV vaccine as well as the calculation of RV vaccine efficacy in
      these populations.

PMID- 8858671
TI  - Six-day amoxicillin vs. ten-day penicillin V therapy for group A streptococcal
      tonsillopharyngitis.
AB  - OBJECTIVE: To compare the efficacy and safety of amoxicillin (50 mg/kg/day
      divided twice daily) for 6 days and penicillin V (45 mg/kg/day divided into three
      doses/day) for 10 days in children with group A streptococcal (GAS)
      tonsillopharyngitis. METHODS: In a prospective, comparative, open, randomized,
      multicenter trial, children were scheduled to return for visits 4 days (main end
      point) and 1 month after the completion of treatment for clinical and
      bacteriologic assessment. Total DNA restriction fragment length polymorphism was
      used to compare pre- and posttreatment GAS isolates. RESULTS: Between September,
      1993, and February, 1995, 321 children (161 amoxicillin, 160 penicillin V) were
      enrolled, among whom 318 (160 amoxicillin, 158 penicillin V) were evaluable for
      safety, and 277 were evaluable for efficacy. Four days after the completion of
      treatment, pretreatment GAS were eradicated from 118 of the 141 children
      receiving amoxicillin (83.7%) and 116 of the 136 (85.3%) taking penicillin. One
      month after the outset of treatment, bacteriologic relapses were observed in 9.9%
      (n = 11) of the children receiving amoxicillin and 5.7% (n = 6) of those treated
      with penicillin V, bacteriologic recurrences in 5 and 3 patients, respectively.
      Adverse events related to the study medications were reported in 4 patients in
      the amoxicillin group and 8 in the penicillin V group. Drug-related adverse
      events leading to treatment discontinuation occurred in 3 patients, all in the
      penicillin V group. Compliance, based on diary cards and the weight of study
      drugs returned, was significantly better in the amoxicillin group. CONCLUSIONS.
      The efficacy and safety of amoxicillin (50 mg/kg/day twice daily) for 6 days were
      not statistically different from those of penicillin (45 mg/kg/d three times a
      day) for 10 days in the treatment of GAS tonsillopharyngitis.

PMID- 8858672
TI  - Acoustic reflectometry: spectral analysis and the conductive hearing loss of
      otitis media.
AB  - OBJECTIVE: To test the hypothesis that the quality of sound reflected from the
      tympanic membrane with acoustic reflectometry is predictive of hearing loss
      caused by otitis media. METHODS: A pediatrician in solo primary care practice
      examined 257 patients for middle ear disease using clinical criteria,
      tympanometry and an acoustic reflectometer with a recording device. Each ear was
      diagnosed as normal, acute otitis media or otitis media with effusion. Hearing
      testing with a select picture audiometer was performed by a technician who was
      blinded to the diagnosis. Paired data were obtained on some ears. RESULTS: A
      spectrum of < 95 degrees identified 100% of the ears hearing at 30 dB or more
      because of otitis media. Paired data were obtained on 99 ears with otitis media
      that failed audiometry on the initial visit. On return 96 of the 99 showed a
      broader spectrum of reflected sound with improved hearing and clinical
      improvement of otitis media. CONCLUSIONS: Measurement of the width of the
      spectrum of reflected sound is the basis for a new technology that shows initial
      promise for being able to provide objective information about the probability of
      conductive hearing loss caused by otitis media.

PMID- 8858674
TI  - Human herpesvirus 6: primary infection and the central nervous system.

PMID- 8858673
TI  - Antibody persistence after primary measles-mumps-rubella vaccine and response to
      a second dose given at four to six vs. eleven to thirteen years.
AB  - BACKGROUND: Since 1989 the American Academy of Pediatrics and the ACIP have
      recommended a second dose of measles-mumps-rubella vaccine (M-M-R-II) at either
      school entry or age 11 to 13 years. Unfortunately few studies are available to
      compare responses to vaccine at the two ages. We performed a prospective trial to
      determine the persistence of antibody to measles, mumps and rubella vaccination
      in two age groups and the response to a second dose given at either 4 to 6 or 11
      to 13 years. METHODS: Thirty-eight children 4 to 6 years old and 57 children 11
      to 13 years old were given a second dose of M-M-R-II as they presented for yearly
      examinations. All had received the first dose at > or = 15 months of age. Measles
      and rubella antibody were measured by enzyme-linked immunosorbent assay (ELISA)
      and neutralizing antibody (NT) assay, and mumps antibody was measured by an ELISA
      method only. An IgM-ELISA antibody assay for measles was used in selected
      children. Prevaccination and 3- to 4-week post-vaccination sera were obtained.
      Measles ELISA, measles-neutralizing antibody (NT) and rubella-neutralizing
      antibody (NT) assays were performed in all children. Seventy-nine of the 95
      children had sufficient sera for repeat measles tests, as well as mumps and
      rubella ELISA determinations. RESULTS: Before the second dose ELISA
      seropositivity rates for measles and mumps were not significantly different
      between the two groups. Rubella ELISA seropositivity was 67% in 11- to 13-year
      olds, compared with 90% in 4- to 6-year-olds (P < 0.01), suggestive of waning
      immunity. Rubella NT seropositivity was also lower in 11- to 13-year-olds than in
      4- to 6-year-olds (63% vs. 100%, P < 0.01). After revaccination, 100% of the
      children become seropositive for all 3 antibodies. We performed measles IgM-ELISA
      testing on all 17 measles-seronegative children, as well as 15 seropositive
      children and 19 children who were 1 month postvaccination with the first M-M-R-II
      at 15 months. The purpose was to determine whether the seronegative children were
      primary or secondary failures. Five of the 17 children with undetectable pre
      second dose antibody made IgM measles antibody after revaccination, suggesting
      that they were primary vaccine failures. CONCLUSIONS: Because all children became
      seropositive after revaccination, the age of administration can be based on the
      convenience of vaccine scheduling. However, in view of the apparent decline in
      rubella antibodies at 11 to 13 years, future studies of rubella vaccination
      should address the issue of whether earlier boosting leads to greater
      susceptibility at the time of reproductive age.

PMID- 8858675
TI  - Epidemiology of tuberculosis among children in the United States: 1985 to 1994.

PMID- 8858676
TI  - Ventricular fluid pleocytosis in children with ventriculoperitoneal shunts.

PMID- 8858677
TI  - Haemophilus influenzae type b meningitis in a fully immunized child with a
      cerebrospinal fluid shunt.

PMID- 8858678
TI  - Clostridium perfringens meningitis in a newborn infant.

PMID- 8858679
TI  - Pseudomonas osteomyelitis after a plantar puncture wound through a rubber sandal.

PMID- 8858680
TI  - Micrococcus luteus as a cause of recurrent bacteremia.

PMID- 8858681
TI  - Disseminated Mycobacterium avium complex presenting as hematochezia in an infant
      with rapidly progressive acquired immunodeficiency syndrome.

PMID- 8858682
TI  - False positive detection of group A Streptococcus antigen resulting from cross
      reacting Streptococcus intermedius (Streptococcus milleri group).

PMID- 8858683
TI  - Generalized lymphadenopathy as initial presentation of toxocariasis in a seven
      year-old boy.

PMID- 8858684
TI  - Role of buffy coat examination in the diagnosis of neonatal candidemia.

PMID- 8858685
TI  - Unsuspected hepatosplenic involvement in patients hospitalized with cat-scratch
      disease.

PMID- 8858686
TI  - Fever, hepatosplenomegaly and rash in a newborn.

PMID- 8858687
TI  - Vibrio cholerae O1 meningitis in an immunosuppressed child.

PMID- 8858688
TI  - Cefotaxime failure in pneumococcal meningitis caused by a susceptible isolate.

PMID- 8858689
TI  - Differentiation of bone infarct from infection in a child in sickle cell disease.

PMID- 8858690
TI  - Challenges in the management of serious infections in pediatric patients.

PMID- 8858691
TI  - Pharmacokinetic determinants of carbapenem therapy in neonates and children.

PMID- 8858692
TI  - Use of carbapenems and other antibiotics for pulmonary infections in patients
      with cystic fibrosis.

PMID- 8858693
TI  - Empirical treatment of fever in neutropenic children: the role of the
      carbapenems. International Antimicrobial Therapy Cooperative Group of the
      European Organisation for Research and Treatment of Cancer and the Gimema
      Infection Program.

PMID- 8858694
TI  - Efficacy, safety and tolerability of meropenem as empiric antibiotic therapy in
      hospitalized pediatric patients.

PMID- 8858695
TI  - Perioperative blood loss: the effect of valproate.
AB  - The purpose of this investigation was to determine the effect of the use of
      valproate (VPA) on bleeding and requirement for replacement blood products in
      patients undergoing major surgical procedures. One hundred thirty-nine patients
      had posterior spinal fusion performed by 1 of 3 surgeons at our institution from
      1987 to 1993. The clinical status of the patient, pre- and postoperative
      laboratory values, type and extent of instrumentation, surgeon performing the
      procedure, and medications (including VPA) were variables considered. The outcome
      measures were intra- and postoperative blood loss and number of blood products
      used. Intraoperative blood loss was correlated with the method of
      instrumentation, platelet count, and the surgeon performing the procedure.
      Postoperative blood loss was correlated with the diagnosis of cerebral palsy. By
      hierachical stepwise regression analysis, the only outcome measure correlated
      with VPA was the number of blood products used.

PMID- 8858696
TI  - Confusional migraine in childhood.
AB  - The aim of this retrospective study was to analyze data obtained from cases with
      acute confusional migraine and compare them with those of other series. Data were
      abstracted from files of 76 patients with a discharge diagnosis of migraine
      admitted to British Columbia Children's Hospital, Vancouver, Canada, between
      January 1982 and September 1990. Of the 76 patients, 13 manifested confusional
      migraine (ratio of males to females was 11:2). The age ranged between 6 and 15
      years (mean age 10.8 years). All patients reported headache and confusion. The
      duration of confusion was 2-24 hours. Other findings included a positive history
      of mild head trauma (4 patients), agitation (8 patients), past history of
      headache (7 patients), family history of migraine on the maternal side (10
      patients), and history of migraine on both sides of the family (1 patient). CT
      scans were performed on 11 patients; 10 were reported to be normal, and 1 patient
      presented an arachnoid cyst. EEGs performed on 4 patients disclosed mild
      abnormality in 2. Cerebrospinal fluid, studied in 2 patients, was normal.
      Management of a child with confusional migraine must take into consideration
      underlying causes, such as seizures, encephalitis, and substance abuse.

PMID- 8858697
TI  - Brainstem frequency-following responses in Rett syndrome.
AB  - The brainstem frequency-following response (FFR) is a short-latency evoked
      response that reflects waveform properties of periodic auditory stimuli. Unlike
      neural activity evoked by transient stimuli, the FFR originates in phase-locked
      neurons that provide unique information concerning the early processing of
      auditory inputs. FFRs elicited by a pure tone were recorded from 9 Rett syndrome
      patients (age 26-55 years, mean = 34.4 years) and compared with those of 18
      normal infants (age 2-10 months, mean = 5.0 months), and 113 young adult (age 18
      30 years, mean = 22.2 years) controls. The Rett syndrome pattern indicated
      considerable intersubject latency variability and poor intrasubject repeat
      reliability except for brief FFR components which were consistently synchronized.
      The pattern observed in Rett syndrome was similar in certain respects to that
      observed in infants, but both patterns differed from those of adults, who showed
      larger amplitudes and consistent waveform synchrony. Clinical and neuropathologic
      data indicate developmental arrest rather than a neurodegenerative process in
      Rett syndrome. The present results are consistent with this interpretation.
      Neurophysiologic studies may identify markers that are distinctive in Rett
      syndrome and make it possible to monitor changes with age and disease process.

PMID- 8858698
TI  - Synaptic alterations of anterior horn cells in Werdnig-Hoffmann disease.
AB  - The most characteristic neuropathologic feature of Werdnig-Hoffmann disease is
      degenerative change in the anterior horn cells of the spinal cord, the mechanisms
      of which have not yet been clearly determined. To assess the synaptic changes in
      the motor neurons, we examined immunoreactivities for synaptophysin in the spinal
      cord of 11 patients with Werdnig-Hoffmann disease. Decreased synaptophysin
      immunoreactivity was observed in the anterior horn cell column in all patients
      with Werdnig-Hoffmann disease and correlated with the degree of degenerative
      change in the motor neurons. Synaptophysin immunoreactivity was relatively
      preserved on the surface of the residual anterior horn cells. Both atrophic
      neurons and chromatolytic neurons had dense accumulations of synaptophysin
      immunoreactive products on the surface of the cell body and their proximal
      processes. These observations suggest that synaptic changes in the anterior horn
      cell column are secondary to the degenerative processes of the anterior horn
      cells.

PMID- 8858699
TI  - Seizure susceptibility during recovery from hypercapnia in neonatal dogs.
AB  - Seizure susceptibility during recovery from hypercapnia was investigated in seven
      anesthetized neonatal dogs; 13, 20, or 30% CO2 gas was administered for 30 min
      through a ventilator to result in three levels of hypercapnia in which measured
      PaCO2 values were approximately 70, 100, and 140 mm Hg. Thereafter, the animals
      were allowed to recover for 45 min; during this recovery phase,
      electrocorticography was performed. In five of seven dogs, approximately 1.5 Hz
      slow irregular spike and wave bursts appeared at 6 min after abrupt withdrawal
      from hypercapnia and lasted several minutes. This seizure activity was followed
      by a brief period of electrical suppression. This phenomenon was most often
      observed during the recovery from moderate hypercapnia and between the PaCO2
      values of 100 and 50 mm Hg. When seizure activities appeared in the
      electrocorticogram, arterial blood pressure increased -40 mm Hg from the
      preseizure level. These results suggest that neonatal seizures may occur during
      recovery from hypercapnia.

PMID- 8858700
TI  - Perturbations of cerebral hemodynamics in Kenyans with cerebral malaria.
AB  - The mechanisms of death and neurologic sequelae in African children with cerebral
      malaria are undetermined. Because pathologic features are confined to the
      cerebral vasculature, perturbations in cerebral hemodynamics may be responsible.
      We compared the transcranial Doppler findings in 50 children with cerebral
      malaria with those of 115 conscious Kenyan children. In addition, 10 children
      with cerebral malaria were studied during intracranial pressure monitoring and
      nine children were studied during the agonal stages. In the children with
      cerebral malaria, cerebral blood flow velocity was increased in 30%, usually
      associated with seizures. Of the 11 children who developed neurologic sequelae,
      six had sonographic abnormalities associated with lateralizing deficits,
      including four children with hemiparesis (in two children the contralateral
      middle cerebral artery could not be insonated and two had transient increases in
      blood flow velocity associated with seizures). In the children with severe
      intracranial hypertension, there was a significant linear relationship between
      the cerebral perfusion pressure and blood flow velocity, suggesting that
      autoregulation was impaired. Sonographic features of progressive intracranial
      hypertension, were observed in three children with cerebral malaria who died.
      Perturbations of cerebral hemodynamics are associated with a poor outcome in
      Kenyan children with cerebral malaria.

PMID- 8858701
TI  - Neonatal intracranial hemorrhage due to rupture of arteriovenous malformation.
AB  - Two cases of neonatal intracerebral hemorrhage secondary to rupture of
      arteriovenous malformation are reported and the pertinent literature is reviewed.
      Despite the limited number of cases, review of the literature and our results
      demonstrate that the outcome of surgical removal of an arteriovenous malformation
      in the neonatal period is not as poor as was previously believed.

PMID- 8858702
TI  - Brain and eye pathology in an infant with Down syndrome and tuberous sclerosis.
AB  - The association of tuberous sclerosis with Down syndrome is exceedingly rare. An
      infant with this unusual association is reported with a description of brain and
      ocular abnormalities which were referable to both conditions. There was
      anteroposterior foreshortening of the brain and Brushfield spots in the iris,
      which are described in Down syndrome. The infant, who suffered from a seizure
      disorder, manifested multiple tubers and subependymal candle gutterings in the
      brain as well as bilateral retinal astrocytic hamartomas.

PMID- 8858703
TI  - Unusual case of inflammatory spinal epidural mass (Castleman syndrome).
AB  - Castleman syndrome (giant lymph node hyperplasia) is a rare, heterogeneous
      lymphoproliferative disorder of unknown etiology and pathogenesis. Most cases
      occur as mediastinal masses, although extrathoracic involvement including nodal
      and extranodal locations have been reported. The localized variants (solitary
      lesions) respond well to surgical excision. We report a 10-year-old boy who
      presented with headache, intermittent fever, and progressive weakness of his
      legs. MRI imaging showed an enhancing epidural mass with impingement on the
      spinal cord at the C6-T2 level. Other laboratory abnormalities included anemia,
      hypergammaglobulinemia, increased erythrocyte sedimentation rate, and
      cerebrospinal fluid pleocytosis with slightly increased cerebrospinal protein.
      The mass was partially resected and the histopathology showed lymphoplasmocytic
      infiltration compatible with Castleman syndrome. There was no evidence of
      malignancy. Castleman syndrome is the most likely diagnosis in the presence of
      the associated systemic findings, although the epidural site for
      lymphoplasmocytic inflammation is atypical.

PMID- 8858704
TI  - Lennox-Gastaut syndrome associated with leukoencephalopathy.
AB  - We report a 13-year-old boy with Lennox-Gastaut syndrome (LGS) associated with
      leukoencephalopathy. He was diagnosed with unclassified acute lymphocytic
      leukemia at the age of 3 years. After initial chemotherapy, he received
      intravenous methotrexate (total dosage 1,035 mg), intrathecal methotrexate (total
      dosage 221 mg), and whole brain irradiation (2,400 cGy). From about the age of 8
      years, he developed slurred speech, hyperactivity, and mental deterioration.
      Cranial CT revealed calcification of the subcortical white matter. At age 9
      years, he exhibited tonic seizures and atonic seizures. EEG showed diffuse slow
      spike-wave discharges, which are characteristic of LGS. Although multiple
      antiepileptic drugs have been prescribed, the frequency of seizures remains
      unchanged and his mental state is becoming progressively worse.

PMID- 8858705
TI  - Baclofen for chronic hiccups.
AB  - Chronic hiccups is a rare occurrence but can be debilitating for the patient.
      Successful intervention is seldom reported. The present case is a young adult who
      had severe almost continuous hiccups for 3 years after placement of a feeding
      gastrostomy and Nissen fundoplication. Within weeks of initiation of baclofen
      treatment, the hiccups ceased. Recurrences of hiccups have responded to increases
      in baclofen dosage.

PMID- 8858706
TI  - Early-onset myopathy with tubular aggregates.
AB  - We report a 14-year-old girl with early onset of slowly progressive muscular
      weakness and atrophy. There was no family history of neuromuscular disease. A
      persistent increase of serum creatine kinase was found. Muscle biopsy specimens
      showed type 1 fiber predominance and tubular aggregates in almost every fiber.
      The clinical findings and pathology suggest that the disease represents one
      variant in a group of rare myopathies with different patterns of inheritance,
      characterized by slowly progressive muscle weakness and tubular aggregates.

PMID- 8858707
TI  - Leigh syndrome associated with mitochondrial DNA 8993 T-->G mutation and ragged
      red fibers.
AB  - We report a 6-month-old girl with episodic hyperventilation, myoclonus, disturbed
      consciousness, and lactic acidosis. Brain sonogram revealed progressive
      ventriculomegaly, and MRI showed symmetric low densities over the putamen
      bilaterally with diffuse cortical cystic lesions. Ragged-red fibers were noted in
      the muscle biopsy. Molecular analysis revealed a heteroplasmic T-->G mutation at
      nucleotide position (np) 8993 of mitochondrial DNA (mtDNA). The proportion of the
      mutant mtDNA in the muscle of the proband was estimated to be 86%. Her mother and
      maternal uncle also harbored the same mutant mtDNA (54 and 48% in their
      leukocytes, respectively). One of her sisters carried 64% mutant mtDNA in her
      leukocytes, but another sister did not. These results suggest that this mutant
      mtDNA is transmitted through the maternal lineage in this family in a randomly
      segregated manner. To our knowledge, this is the first report of a Chinese
      patient with Leigh syndrome associated with the T-->G substitution at np 8993 of
      mtDNA.

PMID- 8858708
TI  - Bilateral internal carotid artery agenesis in a child with psychomotor
      developmental delay.
AB  - In a 2-year-old boy with severe psychomotor developmental delay and a dysmorphic
      face, a chromosome study revealed a balanced translocation: 46XY,t
      (1;3)(p31.2;p21). With magnetic resonance angiography, bilateral internal carotid
      artery agenesis was diagnosed. Periventricular high-intensity areas were evident
      on T2-weighted imaging, but no major cerebral malformation was observed.

PMID- 8858709
TI  - Association of Krabbe leukodystrophy and congenital fiber type disproportion.
AB  - Hypotonia and weakness developed in a 12-month-old boy whose psychomotor
      development had previously been normal. The muscle biopsy demonstrated a
      disparity in the mean diameters of type 1 and type 2 fibers and satisfied major
      histologic criteria for diagnosis of congenital fiber type disproportion (CFTD).
      However, deterioration of motor and mental function, which developed
      subsequently, strongly suggested progressive encephalopathy. Examination of
      leukocyte cerebral enzymes at 15 months of age revealed a complete lack of
      galactosylceramide-beta-galactosidase. Selective type 1 fiber atrophy with type 1
      fiber predominance has been observed in various conditions, including Krabbe
      disease. We report an additional case of Krabbe leukodystrophy associated with
      CFTD. The finding on the molecular level will resolve the dilemma of whether CFTD
      is a congenital myopathy or whether these patterns of disproportion may result
      from a number of different processes that interfere with the maturation of the
      developing motor unit.

PMID- 8858710
TI  - Long-term survival and temporary clinical improvement in subacute sclerosing
      panencephalitis.

PMID- 8858711
TI  - Long-term use of benzodiazepines: tolerance, dependence and clinical problems in
      anxiety and mood disorders.
AB  - This paper reviews the literature on the epidemiological, biological and clinical
      features of benzodiazepine dependence and withdrawal syndrome, focusing on
      clinical problems associated with the long-term use of benzodiazepine (BZs) in
      mood and anxiety disorders. These conditions represent the most frequent mental
      disorders for which BZs are overprescribed. In addition to dependence and
      withdrawal phenomena, the presence of chronic subtle toxicity and the
      interference with the underlying psychopathology observed with BZ use suggests a
      need for a more careful evaluation of the risk-benefit ratio in the long-term
      administration of BZs.

PMID- 8858712
TI  - Effect and efficacy--on the function of models in controlled phase III trials and
      the need for prospective pharmacoepidemiological studies.
AB  - While the "effect" of a drug can be observed or deduced from observational data,
      the concept of "therapeutic efficacy" represents mainly a theoretical
      construction of a high degree of abstraction which is inconceivable without
      reciprocal combination with other theoretical constructs. The "therapeutic
      efficacy" of drugs can be investigated only via clinical-pharmacological or
      clinical "models". Several examples are given and discussed against the
      background of the actual considerations for shortening phase III studies and
      extending pharmacoepidemiological phase IV studies for scientific, practical and
      economic reasons. Of special relevance is the question whether study data of
      phase III allow an extrapolation to the wider patient population which it is
      intended to treat. Thus, it is well known that the criteria for
      representativeness in the investigated population are rarely achieved in phase
      III studies. Furthermore, observations have shown that various intervening
      moderator variables, such as the investigated subgroup or the trial setting (e.g.
      Inpatient or respectively out-patient treatment), might influence therapeutic
      efficacy and the possibility of generalizing the results. This again raises the
      crucial question of clinical relevance of significant effects. Possible ways of
      overcoming this unsatisfactory situation are suggested.

PMID- 8858713
TI  - Ginkgo biloba extract (EGb 761) independently improves changes in passive
      avoidance learning and brain membrane fluidity in the aging mouse.
AB  - Decreases in cell membrane fluidity may be a major mechanism of age-related
      functional decline. A prime cause for the decline of membrane fluidity may be the
      presence of free radicals. Gingko biloba extract EGb 761 protects neuronal cell
      membranes from free radical damage in vitro. Further, EGb 761 has repeatedly been
      shown to improve cognitive functions in man and in laboratory animals. To test if
      there is a link between these two actions we assessed the effects of EGb 761 on
      passive avoidance learning and on neuronal membrane fluidity in vivo in young
      (three-month-old), middle-aged (12-month-old) and aged (22 to 24-month-old)
      female NMRI mice. The animals were treated daily with 100 mg/kg EGb 761 for three
      weeks. There was a significant improvement in short-term memory, measured by the
      avoidance latency 60 seconds after the aversive stimulus (p < 0.0311), and of
      membrane fluidity (p < 0.01) in the aged animals, but no improvement in long-term
      memory as measured by the avoidance latency 24 hours after shock. However, no
      significant correlation between membrane fluidity and short-term memory
      performance was found. Taken together, these results indicate that EGb 761
      independently improves changes in passive avoidance learning and brain membrane
      fluidity.

PMID- 8858714
TI  - Prescribing practice with cognition enhancers in outpatient care: are there
      differences regarding type of dementia?--Results of a representative survey in
      lower Saxony, Germany.
AB  - Previous studies of cognition enhancers have mainly focused on insufficiently
      defined groups of cognition disorders, e.g., "cerebral insufficiency". With
      regard to the various biological changes in senile dementia of Alzheimer's type
      (SDAT) and in vascular dementia (VD), which together make up the great majority
      of senile dementias, many authors have encouraged different studies of these
      types of dementias, especially since both can be diagnosed clinically with
      satisfying certainty. Since primary care physicians treat the majority of elderly
      and demented patients, they have their own experience with cognition enhancers.
      We were therefore interested to know, how far these physicians differ in their
      treatment of SDAT and VD. We performed a representative survey (response rate
      83.2%; 145 family physicians and 14 neuropsychiatrists) in the Goettingen area. A
      written case vignette described a 70-year-old widow with moderate dementia and
      vascular risk factors which are easily treated with drugs. Two versions were
      randomly assigned, in which (version A) either a "typical" VD history or a
      typical SDAT history (version B) were described. After perusal, the physician was
      asked whether and which drugs he would choose to treat the cognitive disorders in
      this patient. Most frequently, piracetam (A/B: 25.6%/30.9%), ginkgo biloba
      (24.4%/28.4%), and nimodipine (14.1%/25.9%) were considered. Aspirin was cited by
      29.5%(A) and 17.3%(B) of the physicians respectively. As far as the type of
      dementia was concerned, significant differences were found only for co
      dergocrine, which was preferred in SDAT. The following inter-group trends were
      observed: family physicians considered ginkgo biloba more often than nimodipine
      or co-dergocrine. The results show the apparent importance of cost-and safety
      aspects, while the type of dementia has hardly any impact. The latter impression
      corresponds to the results of drug trials demonstrating no different efficacy. In
      our opinion, aspirin was not sufficiently taken into consideration.

PMID- 8858715
TI  - Substituting carbamazepine with oxcarbazepine increases citalopram levels. A
      report on two cases.
AB  - The combination of antiepileptic and psychotropic medications is not uncommon.
      The widely used anticonvulsant carbamazepine, however, has been found to induce
      the degradation of many psychiatric drugs. On the contrary, its 10-keto analog
      oxcarbazepine does not have a significant effect on the metabolism of concomitant
      drugs. Consequently, when carbamazepine medication is changed to oxcarbazepine,
      the serum concentrations of various concurrently used drugs may increase,
      resulting in alterations in the therapeutic and toxic response. In this paper we
      describe two patients with comorbid epilepsy, major depression, and panic
      disorder, whose serum citalopram levels increased and antidepressant response
      changed when concurrent carbamazepine treatment was substituted with
      oxcarbazepine.

PMID- 8858716
TI  - Toxic serotonin syndrome or neuroleptic malignant syndrome?
AB  - Administration of medications which affect brain dopamine and serotonin levels
      are occasionally associated with neurotoxic behavioral and autonomic syndromes,
      variously described as the neuroleptic malignant (NMS) and the toxic serotonin
      (TSS) syndromes. Based on concepts of the presumed brain mechanisms of action of
      the drugs, different corrective interventions have been recommended. We describe
      a case of neurotoxic syndrome with characteristics indistinguishable from NMS in
      which the offending agents are those which affect the serotonin and not the
      dopamine systems. The patient recovered with lorazepam and electroconvulsive
      therapy (ECT). We argue that NMS and TSS are examples of a non-specific
      generalized neurotoxic syndrome, and not specific syndromes: and that these are
      subtypes of catatonia. Patients today should be treated with benzodiazepines, and
      if these fail, with ECT, interventions which are effective in relieving
      catatonia.

PMID- 8858717
TI  - Serotonin syndrome with moclobemide-fluoxetine combination.

PMID- 8858718
TI  - Effects of tissue conductivity variations on the cardiac magnetic fields
      simulated with a realistic heart-torso model.
AB  - Cardiac magnetic fields with varying tissue conductivities are simulated. A high
      resolution finite-element torso model composed of 19 tissue types and with a
      voxel resolution of 1.5 mm x 1.5 mm x 3 mm is used. It has a detailed description
      of tissue geometries and therefore is well suited for analysing the effects of
      tissue conductivities on the cardiac magnetic fields. The computed results show
      the greatest sensitivity of the magnetic fields to the changes in the
      conductivity of blood and myocardium, and less significant sensitivity to the
      conductivity of the lungs, muscle, fat and other tissues. These results are
      relevant to future modelling of magnetocardiograms and solving the inverse
      problem. They also emphasize the importance of careful modelling of the blood and
      heart regions, and suggest that less attention needs to be directed to bone or
      fat tissue.

PMID- 8858719
TI  - Dielectric and gravimetric studies of water binding to lysozyme.
AB  - Time domain dielectric spectroscopy and hydration isotherm measurements as a
      function of temperature have been applied to hydrated lysozyme powder. Two
      dielectric dispersions were identified, the first centred at approximately 8 MHz
      and a second above 1 GHz. The higher dispersion is considered to be the result of
      rotational relaxation of water molecules bound to the enzyme. In this case the
      results indicate the existence of a population of 32 water molecules per lysozyme
      molecule which are irrotationally bound to the lysozyme structure. A larger
      population of water molecules is relatively free to respond to the electric field
      and exhibits a dipole moment close to that of vapour phase water molecules. Multi
      temperature hydration isotherm measurements are used to calculate enthalpies and
      entropies associated with the binding of water to lysozyme. Discontinuities both
      in dielectric and in thermodynamic characteristics in the range 10-14% hydration
      are interpreted as a re-ordering of the water structure on the enzyme surface.

PMID- 8858720
TI  - Dosimetric verification of open asymmetric photon fields calculated with a
      treatment planning system based on dose-to-energy-fluence concepts.
AB  - Output normalized dose profiles for asymmetric open photon fields has been
      calculated using a commercial treatment planning system (TPS) based on a dose-to
      energy-fluence concept. The model does not require any additional measurements
      for off-axis fields. Calculations are compared with measurements for quadratic
      fields of 5 cm x 5 cm up to 20 cm x 20 cm, with their geometric field centre
      positioned 10 cm off-axis in the in-plane direction. The measurements include
      depth doses and profiles in-plane as well as cross-plane for nominal photon
      energies of 4, 6 and 18 MV x-rays. Both calculated and measured doses are
      normalized with respect to a 10 cm x 10 cm reference field, therefore making it
      possible to compare not only the relative distributions but also the absolute
      dose levels; that is, calculation of monitor units is included. The calculated
      depth-dose curves are generally in good agreement with measured data with an
      accuracy at the absolute dose level of 2% at depths beyond the dose maximum. The
      cross-plane profiles are calculated with an accuracy better than 3% within the
      field. The 'tilt' towards the collimator central axis of the in-plane profiles is
      predicted by the model, but is somewhat overestimated at large depths. The system
      provides the possibility to separate the primary and scattered parts of the dose
      and the cause of this tilting was studied by comparing calculated phantom
      scattering and head-scattering dose profiles for a symmetric 40 cm x 20 cm field
      to dose profiles for an asymmetric 20 cm x 20 cm field. The tilting is shown to
      originate from a change both in phantom scattering and in head scattering
      compared to the case of symmetrical fields. The results indicate that the
      investigated TPS can calculate dose distributions in open asymmetric fields with
      a high degree of accuracy, typically better than 2-3%.

PMID- 8858721
TI  - On-line exit dose profile measurements by a diode linear array.
AB  - The possibility of using a commercial diode linear array (BMS Schuster Inc.) in
      on-line portal dosimetry has been investigated. The system is composed of 88
      equispaced diodes (distance between diodes, 0.5 cm; detection area, 2.5 x 2.5
      mm2). The ability to measure exit dose profiles has been demonstrated by
      comparing relative exit dose profiles measured by an ionization chamber (NE 2571)
      with 'portal' profiles measured by the diode array on a number of homogeneous and
      inhomogeneous phantoms in 6 MV x-ray beams (from a Clinac Varian 6/100). The
      influence of the variation of the scattered radiation at the exit level with
      respect to the detector level has been discussed and investigated by varying the
      air gap (from 0 to 80 cm for a homogeneous phantom and from 0 to 25 cm for
      inhomogeneous phantoms) as well as the field width. A good agreement (maximum
      difference 3.8%; 2.5% when the array was positioned in contact with the phantoms)
      between 'portal' profiles and exit dose profiles in both homogeneous and
      inhomogeneous phantoms has been found if the array-phantom distance is kept below
      7.5 cm. Results indicate that the system should be suitable for applications in
      transit dosimetry.

PMID- 8858722
TI  - A pencil beam algorithm for proton dose calculations.
AB  - The sharp lateral penumbra and the rapid fall-off of dose at the end of range of
      a proton beam are among the major advantages of proton radiation therapy. These
      beam characteristics depend on the position and characteristics of upstream beam
      modifying devices such as apertures and compensating boluses. The extent of
      separation, if any, between these beam-modifying devices and the patient is
      particularly critical in this respect. We have developed a pencil beam algorithm
      for proton dose calculations which takes accurate account of the effects of
      materials upstream of the patient and of the air gap between them and the
      patient. The model includes a new approach to picking the locations of the pencil
      beams so as to more accurately model the penumbra and to more effectively account
      for the multiple-scattering effects of the media around the point of interest. We
      also present a faster broad-beam version of the algorithm which gives a
      reasonably accurate penumbra. Predictions of the algorithm and results from
      experiments performed in a large-field proton beam are presented. In general the
      algorithm agrees well with the measurements.

PMID- 8858723
TI  - An analytical approximation of depth-dose distributions for therapeutic proton
      beams.
AB  - A simple analytical approximation for the proximal part of the depth-dose
      distribution of a spread-out-Bragg-peak (SOBP) proton beam is derived. The basic
      assumption made is that the range-energy relationship follows a power law. The
      analytical formula depends only on the ratio of the distance from the proximal
      edge of the SOBP and the width of the SOBP. A comparison with measurements and
      with exact numerical calculations reveals a maximum deviation of 5% and a typical
      deviation of less than 2% of the target dose. The model comprises an analytical
      expression for the weighting of individual Bragg peaks as a function of the
      range, which is necessary to obtain an SOBP of the desired width and depth.
      Finally, an analytical expression for the total energy released in normal tissue
      is found by integrating the depth-dose distribution.

PMID- 8858724
TI  - A measurement of the fast-neutron sensitivity of a Geiger-Muller detector in the
      pulsed neutron beam from a superconducting cyclotron.
AB  - The kU value of a commercially available miniature energy compensated Geiger
      Muller (GM) detector has been determined using the modified lead attenuation
      method of Hough. The measurements were made in a d(48.5)-Be neutron beam produced
      by the superconducting cyclotron based neutron therapy facility at Harper
      Hospital. The unique problems associated with making measurements in a 2 ms
      duration pulsed beam with a 20% duty cycle are discussed. The beam monitoring
      system, which allows the beam pulse shape at low beam intensities to be measured,
      is described. By gating the GM output with a discriminator pulse derived from the
      beam pulse shape, the gamma-ray count rates and dead-time corrections within the
      2 ms pulse and between pulses can be measured separately. The kU value of (0.0245
      +/- 0.0015) determined for this GM detector is consistent with the values
      measured by other workers with identical and similar detectors in neutron beams
      with comparable, but not identical, neutron spectra.

PMID- 8858725
TI  - Effective source size, yield and beam profile from multi-layered bremsstrahlung
      targets.
AB  - Modern conformal radiotherapy benefits from heterogeneous dose delivery using
      scanned narrow bremsstrahlung beams of high energy in combination with dynamic
      double focused multi-leaf collimation and purging magnets. When using a purging
      magnet to remove electrons and positrons the target space is limited and
      unorthodox thin multi-layered targets are needed. A computational technique has
      therefore been developed to determine the forward yield and the angular
      distributions of the bremsstrahlung beam as well as the size and location of the
      effective and the virtual photon point source for arbitrary multi-layer
      bremsstrahlung targets. The Gaussian approximation of the diffusion equation for
      the electrons has been used and convolved with the bremsstrahlung production
      process. For electrons with arbitrary emittance impinging on targets of any multi
      layer and atomic number combination, the model is well applicable, at least for
      energies in the range 1-100 MeV. The intrinsic bremsstrahlung photon profile has
      been determined accurately by deconvolving the electron multiple scattering
      process from thin experimental beryllium target profiles. For electron pencil
      beams incident on a target of high density and atomic number such as tungsten,
      the size of the effective photon source stays at around a tenth of a millimetre.
      The effective photon source for low-Z materials such as Be, C and Al is located
      at depths from 3-7 mm in the target, decreasing with increasing atomic number.
      The effective photon source at off-axis positions then moves out considerably
      from the central axis, which should be considered when aligning collimators. For
      high-Z materials such as tungsten, the location of the effective photon source is
      at a few tenths of a millimetre deep. The virtual photon point source is located
      only a few tenths of a millimetre upstream of the effective photon source both
      for high- and low-Z materials. For 50 MeV electrons incident on multi-layered
      full range targets the radial energy fluence distributions will have a full width
      at half maximum (FWHM) of 80 to 100 mm at 1 m from the target. The best target
      composition made of two layers when the space is limited to 15 mm was found to be
      9 mm-Be followed by 6 mm W. A thin beryllium target (approximately 3 mm) results
      in a high-intensity bremsstrahlung lobe with a FWHM of about 35 mm at the
      isocentre. Interestingly, the forward dose rate in such a beam is as high as 62%
      of the maximum achievable with an optimal target design, even if on average only
      1 MeV is lost by the electrons.

PMID- 8858726
TI  - Time constants in thermal laser medicine: II. Distributions of time constants and
      thermal relaxation of tissue.
AB  - The thermal response of a semi-infinite medium in air, irradiated by laser light
      in a cylindrical geometry, cannot accurately be approximately by single radial
      and axial time constants for heat conduction. This report presents an analytical
      analysis of hear conduction where the thermal response is expressed in terms of
      distributions over radial and axial time constants. The source term for heat
      production is written as the product of a Gaussian shaped radial term and an
      exponentially shaped axial term. The two terms are expanded in integrals over
      eigenfunctions of the radial and axial parts of the Laplace heat conduction
      operator. The result is a double integral over the coupled distributions of the
      two time constants to compute the temperature rise as a function of time and of
      axial and radial positions. The distribution of axial time constants is a
      homogeneous slowly decreasing function of spatial frequency (v) indicating that
      one single axial time constant cannot reasonably characterize axial heat
      conduction. The distribution of radial time constants is a function centred
      around a distinguished maximum in the spatial frequency (lambda) close to the
      single radial time constant value used previously. This suggests that one radial
      time constant to characterize radial heat conduction may be a useful concept.
      Special cases have been evaluated analytically, such as short and long
      irradiation times, axial or radial heat conduction (shallow or deep penetrating
      laser beams) and, especially, thermal relaxation (cooling) of the tissue. For
      shallow penetrating laser beams the asymptotic cooling rate is confirmed to be
      proportional to [(t)0.5-(t-tL)0.5] which approaches 1/t0.5 for t >> tL, where t
      is the time and tL is the laser pulse duration. For deep penetrating beams this
      is proportional to 1/(t-tL). For intermediate penetration, i.e. penetration
      depths about equal to spot size diameters, this is proportional to 1/(t-tL)1.5.
      The double integral has been evaluated numerically and the results have been
      compared with the various approximations available including the new results and
      the single time constant model. The present analysis completes our previous work,
      presents a closed-form formulation for the non-ablative thermal response of laser
      irradiated tissue and provides insight into the practical value of using time
      constants for representing heat conduction effects, in particular for the rate of
      cooling of the tissue surface.

PMID- 8858727
TI  - Planar imaging quantification using 3D attenuation correction data and Monte
      Carlo simulated buildup factors.
AB  - A new method to correct for attenuation and the buildup of scatter in planar
      imaging quantification is presented. The method is based on the combined use of
      3D density information provided by computed tomography to correct for attenuation
      and the application of Monte Carlo simulated buildup factors to correct for
      buildup in the projection pixels. CT and nuclear medicine images were obtained
      for a purpose-built nonhomogeneous phantom that models the human anatomy in the
      thoracic and abdominal regions. The CT transverse slices of the phantom were
      converted to a set of consecutive density maps. An algorithm was developed that
      projects the 3D information contained in the set of density maps to create
      opposing pairs of accurate 2D correction maps that were subsequently applied to
      planar images acquired from a dual-head gamma camera. A comparison of results
      obtained by the new method and the geometric mean approach based on published
      techniques is presented for some of the source arrangements used. Excellent
      results were obtained for various source-phantom configurations used to evaluate
      the method. Activity quantification of a line source at most locations in the
      nonhomogeneous phantom produced errors of less than 2%. Additionally, knowledge
      of the actual source depth is not required for accurate activity quantification.
      Quantification of volume sources placed in foam, Perspex and aluminium produced
      errors of less than 7% for the abdominal and thoracic configurations of the
      phantom.

PMID- 8858728
TI  - Quantification of intensity variations in functional MR images using rotated
      principal components.
AB  - In functional MRI (fMRI), the changes in cerebral haemodynamics related to
      stimulated neural brain activity are measured using standard clinical MR
      equipment. Small intensity variations in fMRI data have to be detected and
      distinguished from non-neural effects by careful image analysis. Based on
      multivariate statistics we describe an algorithm involving oblique rotation of
      the most significant principal components for an estimation of the temporal and
      spatial distribution of the stimulated neural activity over the whole image
      matrix. This algorithm takes advantage of strong local signal variations. A
      mathematical phantom was designed to generate simulated data for the evaluation
      of the method. In simulation experiments, the potential of the method to quantify
      small intensity changes, especially when processing data sets containing multiple
      sources of signal variations, was demonstrated. In vivo fMRI data collected in
      both visual and motor stimulation experiments were analysed, showing a proper
      location of the activated cortical regions within well known neural centres and
      an accurate extraction of the activation time profile. The suggested method
      yields accurate absolute quantification of in vivo brain activity without the
      need of extensive prior knowledge and user interaction.

PMID- 8858729
TI  - Pixel driven implementation of filtered backprojection for reconstruction of fan
      beam SPECT data using a position dependent effective projection bin length.
AB  - Filtered backprojection is commonly implemented as a pixel driven algorithm in
      which the density is reconstructed on an array of grid points that are usually
      associated with the centres of square image pixels. In fan beam geometry, this
      conventional pixel driven approach using two-bin linear interpolation leads to an
      inefficient use of the projection data due to magnification at the projection
      line. For typical count limited SPECT data, this results in increased
      reconstructed image noise. We propose an alternative type of pixel driven
      algorithm that makes efficient use of projection data by averaging over all bins
      within a position dependent "effective' projection bin interval. The effective
      bin interval is equivalent to the image pixel length magnified on the projection
      line. This heuristic method leads to more complete use of the projection data and
      results in reconstructed images with superior noise properties compared with the
      conventional method while presenting similar spatial resolution characteristics.

PMID- 8858730
TI  - Strategies to improve 3D whole-body PET image reconstruction.
AB  - An algorithm is described for three-dimensional whole-body (3DWB) image
      reconstruction in positron emission tomography. For whole-body applications,
      improvements to the popular fixed-axial-acceptance-angle technique are achieved
      by combining axially adjacent projection data available with a long-axis data
      set. Time-consuming reprojection of unmeasured oblique lines of response is
      reduced or eliminated by axial overlap of bed positions, while pixel variance and
      reconstructed axial resolution are made more uniform by the overlap. Improvements
      in noise and resolution uniformity are accompanied by gains in reconstruction
      efficiency, and may be optimized against increased acquisition-time due to
      overlapping acquisition segments and reduced axial coverage. An 11-detector-ring
      overlap improves axial uniformity in coronal images of a long, uniform cylinder
      from 23% to 8% with uniform axial resolution. Associated with a 37% improvement
      in reconstruction time is a 34% reduction in axial coverage for four bed
      positions. A smaller degree of overlap is found to provide the best trade-off
      between image uniformity, total scan duration, and reconstruction time because of
      a proportionally greater reduction in reprojected lines of response. Using a
      sample optimization scheme, we find a three-ring overlap is best for a 60 cm
      axial field of view and a five-ring overlap for an 80 cm axial field of view.

PMID- 8858731
TI  - Linear dimension reduction of sequences of medical images: III. Factor analysis
      in signal space.
AB  - A method is presented for improving the precision of factor analysis by utilizing
      physiological information. The first step is an optimal linear dimension
      reduction, whereby the data are projected onto a low-dimensional signal space.
      Then principal component analysis is performed in the signal space rather than in
      the entire data space. This improves the precision of the principal components.
      Unlike ordinary principal component analysis, the present method is not degraded
      when the time intervals are subdivided, provided that the signal space is
      correct. Alternatively, but with identical results, the covariance matrix can be
      calculated from the whole data space. The covariance matrix is then transformed
      and principal component analysis is performed in either a low-rank matrix or a
      low-dimensional submatrix instead of in the whole covariance matrix. Factor
      analysis using the intersection method with a theory space may be improved by
      employing the present method. In simulations based on a [11C]flumazenil study
      with 27 frames, the proposed method required only 58 per cent of the
      radioactivity to produce the same precision as the intersection method and only
      27 per cent when compared to ordinary principal component analysis.

PMID- 8858732
TI  - Optical image reconstruction using DC data: simulations and experiments.
AB  - In this paper, we explore optical image formation using a diffusion approximation
      of light propagation in tissue which is modelled with a finite-element method for
      optically heterogeneous media. We demonstrate successful image reconstruction
      based on absolute experimental DC data obtained with a continuous wave 633 nm He
      Ne laser system and a 751 nm diode laser system in laboratory phantoms having two
      optically distinct regions. The experimental systems used exploit a tomographic
      type of data collection scheme that provides information from which a spatially
      variable optical property map is deduced. Reconstruction of scattering
      coefficient only and simultaneous reconstruction of both scattering and
      absorption profiles in tissue-like phantoms are obtained from measured and
      simulated data. Images with different contrast levels between the heterogeneity
      and the background are also reported and the results show that although it is
      possible to obtain qualitative visual information on the location and size of a
      heterogeneity, it may not be possible to quantitatively resolve contrast levels
      or optical properties using reconstructions from DC data only. Sensitivity of
      image reconstruction to noise in the measurement data is investigated through
      simulations. The application of boundary constraints has also been addressed.

PMID- 8858733
TI  - Characteristics of secondary electrons produced by 6, 10 and 24 MV x-ray beams.
AB  - Megavoltage x-ray beams generated by linear accelerators (linacs) deliver their
      maximum dose a few centimetres below the treatment or phantom surface. This skin
      sparing effect is degraded by the generation of secondary electrons as the x-ray
      beam passes to the patient or phantom. This work measures the characteristics of
      these electrons. A light-weight electromagnet was constructed that could be
      mounted in the block-tray position, 58 cm from the x-ray source of a Varian
      Clinac 2100C or 2500 linac. A field strength as high as 0.1500 T was generated,
      which was strong enough to sweep secondary electrons out of a 10 cm x 10 cm
      field. For 6, 10 and 24 MV x-ray beams, secondary contamination electrons
      produced 18, 38 and 65% of the surface dose, corresponding to 3, 5 and 12% of the
      maximum dose, respectively. A parameterized depth-dose curve for the
      contamination electrons was produced and was valid for all the x-ray energies
      studied.

PMID- 8858734
TI  - Calculating the angular standard deviation of electron beams using Fermi-Eyges
      theory.
AB  - Knowledge of the angular distribution of an electron beam at the applicator face
      is a necessary parameter in defining a beam when the Hogstrom pencil beam method
      of dose calculation is used. The angular spread can be found experimentally using
      penumbra widths measured at various distances from the applicator face. Using
      knowledge of the geometry and composition of the scattering foils of the linear
      accelerator, the angular standard deviation was calculated theoretically using
      Fermi-Eyges theory. The obtained angular spread values agree with experimentally
      derived values to within experimental error for electron energies from 6 to 21
      MeV. The Fermi-Eyges calculation is fast, and can be used as a quick check to
      validate experimental angular spread values.

PMID- 8858735
TI  - Comments on 'Problems associated with the use of broad-band illumination sources
      for photodynamic therapy'.

PMID- 8858736
TI  - Comments on 'Problems associated with the use of broad-band illumination sources
      for photodynamic therapy'.

PMID- 8858737
TI  - Comments on 'The calibration of CT Hounsfield units for radiotherapy treatment
      planning'.

PMID- 8858738
TI  - Comments on the measurement of radionuclide mixtures.

PMID- 8858739
TI  - The diagnosis and management of splanchnic artery aneurysms.

PMID- 8858740
TI  - Helicobacter pylori infection in non-ulcer dyspeptic and ulcer patients.
      Determinants and consequences in 'real life'.
AB  - BACKGROUND: Infection rates are high in patients with ulcer disease, but even non
      ulcer dyspepsia (NUD) patients have Helicobacter pylori infection. The Notodden
      Helicobacter study is an 'outcome study' of clinical practice in a local
      hospital. The study may identify factors associated with infection and evaluate
      whether H. pylori infection predicts symptoms in both ulcer disease and NUD.
      METHODS: Base-line results on infection, symptoms, endoscopy, and treatment were
      registered in 587 ulcer and NUD patients. H. pylori status was assessed with a
      rapid urease test. Questionnaire data (5-43 months after treatment) give
      information about symptoms. Regression models to identify H. pylori status were
      developed. RESULTS: Ulcer patients (H. pylori +/-) were similar to infected NUD
      patients. In contrast, uninfected NUD patients were younger, had less severe
      symptoms, and used less medication than other patients. In NUD, infection rate
      increased with epigastric pain, male sex, and age. CONCLUSION: From a local
      hospital's point of view, H. pylori-infected NUD patients are like ulcer patients
      with regard to symptoms and demographics. The results suggest that H. pylori
      infection may give dyspeptic symptoms through other mechanisms than ulcer. We
      propose a division of the NUD group into HINUD (Helicobacter-infected NUD) and
      NINUD (non-infected NUD).

PMID- 8858741
TI  - Seroprevalence of Helicobacter pylori infection in medical staff in Shanghai.
AB  - BACKGROUND: The epidemiology of Helicobacter pylori is still under investigation.
      It is postulated that the human stomach is the natural reservoir and that spread
      occurs by oral-oral or fecal-oral transmission. The aim of this study was to
      determine whether medical staff, especially endoscopy unit personnel, are at an
      increased risk of acquiring H. pylori infection. METHODS: An enzyme-linked
      immunosorbent assay technique was used to detect circulating H. pylori IgG
      antibodies in 1050 medical staff from 16 hospitals in Shanghai, including 125 GI
      endoscopists, 45 endoscopy unit nurses, 71 gastroenterologists not doing
      endoscopy, 105 nurses working in gastroenterology wards, 417 internists, and 287
      general nurses. This group was compared with an age-matched population obtained
      from the same urban area of the city. RESULTS: The overall prevalence of H.
      pylori infection in total medical staff was 70.0%, compared to 44.6% in general
      population (P < 0.0001). Age-adjusted comparisons between subgroups of medical
      staff were made. The prevalence of H. pylori in GI endoscopists was 82.4%, which
      is significantly higher than 66.4% in internists and 65.8% in general nurses
      (all, P < 0.01) but not significantly different from 77.7% in endoscopy unit
      nurses or from 74.2% in nurses working in gastroenterology wards (all, P > 0.05).
      Further analysis did not show any significant difference in the prevalence of H.
      pylori between other subgroups. The prevalence of H. pylori infection in GI
      endoscopists increased with the number of years of practice. CONCLUSIONS: Medical
      staff, especially endoscopy unit personnel, are at increased risk of infection
      with H. pylori. These findings strongly suggest the medical practice and
      endoscopy procedures are risk factors for H. pylori infection and support person
      to-person transmission in this setting, probably from patients to medical staff.

PMID- 8858742
TI  - Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients
      receiving continuous non-steroidal anti-inflammatory drug therapy. A Nordic
      multicentre study.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause
      gastroduodenal lesions and dyspeptic symptoms. METHODS: Patients with a history
      of dyspepsia or uncomplicated peptic ulcer disease and with a need for continuous
      NSAID treatment were randomized to receive either 20 mg omeprazole once daily or
      placebo. Gastroduodenal ulcers, erosions, and dyspeptic symptoms were evaluated
      after 1 and 3 months. RESULTS: During a 3-month study period 4.7% (4 of 85) of
      omeprazole-treated patients developed peptic ulcer, compared with 16.7% (15 of
      90) of patients treated with placebo. This prophylactic effect of omeprazole was
      sustained independently of previous peptic ulcer history or Helicobacter pylori
      status. Development of dyspeptic symptoms requiring active treatment, either
      alone or in combination with ulcer(s) or erosions, occurred in 15.3% (15 of 85)
      of patients treated with omeprazole and 35.6% of those who received placebo.
      CONCLUSIONS: Omeprazole, 20 mg once daily, provides effective prophylactic
      therapy in patients at risk of developing NSAID-associated peptic ulcers or
      dyspeptic symptoms.

PMID- 8858743
TI  - IgA antiendomysial antibodies on the umbilical cord in diagnosing celiac disease.
      Sensitivity, specificity, and comparative evaluation with the traditional kit.
AB  - BACKGROUND: The possibility of assaying antiendomysial antibodies (EmA) on the
      human umbilical cord instead of monkey esophagus has recently been suggested. We
      therefore evaluated in patients with celiac disease (CD) the sensitivity and
      specificity of EmA and of antigliadin antibodies (AGA) for both umbilical cord
      and monkey esophagus. METHODS: We studied 36 patients with CD and atrophy of the
      intestinal mucosa (median age, 1.4 years), 14 patients with CD on gluten-free
      diet for 8-12 months (median age, 3.0 years), 36 controls without
      gastrointestinal disease (median age, 4.0 years), and 72 patients with cow's milk
      protein enteropathy (CMPE) (median age, 1.2 years). AGA and EmA on monkey
      esophagus were assayed with commercially available kits; the slides with
      umbilical cord were prepared in our laboratory. RESULTS: There was a perfect
      concordance between EmA results evaluated on umbilical cord and those on monkey
      esophagus; there was a doubtful result in only one case on human umbilical cord,
      which was positive with low titer on monkey esophagus. EmA specificity was 100%;
      the specificity of AGA IgG varied between 72% and 94% and of AGA IgA between 90%
      and 100% depending on whether controls without gastrointestinal disorders or
      patients with CMPE were considered. EmA sensitivity was 97%, AGA IgG was 89%, and
      AGA IgA 72% sensitive. The only false negative for EmA was positive for AGA IgG
      and AGA IgA. CONCLUSIONS: Using human umbilical cord as a substrate for EmA may
      provide the same sensitivity and specificity as offered by the test using monkey
      esophagus substrate, thus reducing costs and avoiding the use of endangered
      species.

PMID- 8858744
TI  - The role of an open-access bleeding unit in the management of colonic
      haemorrhage. A 2-year prospective study.
AB  - BACKGROUND: Major colonic haemorrhage poses difficult diagnostic and therapeutic
      problems and, in contrast to upper gastrointestinal bleeding, has no generally
      accepted plan of management. METHODS: We report community-based prospective data
      accumulated over 2 years (1991-93) on 1602 patients referred to an open-access
      bleeding unit with suspected gastrointestinal haemorrhage. RESULTS: Of 278 (17%)
      admissions with suspected lower GI haemorrhage, 252 were confirmed. Forty-eight
      per cent were defined as "significant' bleeds, with a decrease in haemoglobin and
      cardiovascular compromise. Of 102 significant bleeds in subjects more than 60
      years old, 29% rebled, and 12.6% required emergency surgery. Diverticular disease
      (24%) was the commonest diagnosis, with tumours, infective colitis, and
      inflammatory colitis each at 10%. The overall 30-day mortality for colonic
      bleeding was 5.1% (13 of 252), with only 1 death occurring in the group less than
      60 years old. CONCLUSIONS: This study provides a unique database for the natural
      history of colonic bleeding and its management within the setting of a
      specialized bleeding unit.

PMID- 8858745
TI  - Colectomy for severe slow-transit constipation in strictly selected patients.
AB  - BACKGROUND: Colectomy for severe constipation has in up to 25% of patients given
      unsatisfactory results. Failure to cure constipation is in most patients due to
      rectal dysfunction. The aim of the present study was to evaluate the effect of
      colectomy in a group of patients who fulfil all the criteria which, with our
      present knowledge, should predict a favourable result. METHODS: Twelve patients
      with long-standing severe constipation incurable by dietary regulation and
      medical treatment with demonstrable slow-transit constipation and normal rectal
      function entered the study. RESULTS: Ten patients were relieved of their
      constipation. Two patients continued to be constipated after subtotal colectomy.
      One had a very highly compliant rectum (preoperatively) with a maximal tolerable
      volume of 700 ml but normal emptying at defecography and normal emptying of
      viscous fluid. The patient was subsequently treated with proctectomy and ileo
      pouch-anal anastomosis with satisfactory result. One patient with opioid abuse
      due to abdominal pain was improved by the operation but was still constipated.
      The opioid abuse continued, however, after the operation owing to continuing
      abdominal pain. A further three patients complained of abdominal pain, and two
      developed diarrhoea, one of whom became incontinent. CONCLUSION: Subtotal or
      segmental colectomy should be considered in a small number of patients with
      severe constipation provided strict criteria are fulfilled. Excessively high
      rectal volume tolerability may in spite of normal emptying capacity indicate the
      risk of development of rectal inertia postoperatively and may be a
      contraindication for surgery.

PMID- 8858746
TI  - Evaluation of the role of mast cells in the progression of acetic acid-induced
      colitis in mice.
AB  - BACKGROUND: Mast cells are widely distributed in the gastrointestinal mucosa.
      However, their role in the pathogenesis of inflammatory bowel disease remains
      unsettled. The aim of the present study is to clarify the relative importance of
      mast cells in the progression of acetic acid-induced colitis in mice. METHODS:
      Mast cell-deficient W/Wv and their normal littermate +/+ mice were given
      intrarectal administration of 5% acetic acid. The severity of colonic damage, the
      number of mast cells, and myeloperoxidase (MPO) activities in the colonic tissues
      were examined. RESULTS: The severity of colonic damage was comparable between
      W/Wv and +/+ mice. In both groups of animals kinetic changes of the severity of
      the mucosal damage agreed well with that of MPO activities in the colonic mucosa.
      Pretreatment with a mast cell stabilizer, ketotifen, did not affect the severity
      of colitis in +/+ mice. CONCLUSIONS: These results discount, but do not disprove,
      the role of mast cells in the progression of acetic acid-induced colitis in mice.

PMID- 8858747
TI  - Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in
      Crohn's disease. A randomized controlled multicenter trial. Study Group Members
      (German Crohn's Disease Study Group).
AB  - BACKGROUND: There is no established therapy for maintaining remission in patients
      with Crohn's disease. Following different suggestions from the literature, two
      potential interventions for maintaining remission were tested against placebo,
      using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a
      carbohydrate-reduced diet (84 g/day). METHODS: A total of 204 patients were
      recruited after they had had an acute relapse. After remission (CDAI < or = 150)
      was attained with steroid therapy, patients were randomized to receive either
      omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69). Low-dose
      prednisolone was given to all patients for the first 8 weeks of intervention.
      CDAI and an acute-phase protein (CRP) were used as criteria for a relapse.
      RESULTS: The proportion of patients without relapse within a year were similar in
      the placebo and active treatment group (intention-to-treat analysis: placebo,
      30%; active treatment, 30%; protocol-adhering patients, 29% versus 28%). Patients
      did gain benefit (53%; p = 0.023) for as long as they maintained the diet.
      However, intention-to-treat analysis (diet group, 40%) did not show a noticeable
      difference when compared with placebo. CONCLUSIONS: Omega-3 fatty acids did not
      show an effect on extending the remission in Crohn's disease. For the diet
      patients the question remains whether the noncompliant patients dropped out early
      because they sensed a relapse approaching or whether their condition deteriorated
      because they failed to comply with the diet.

PMID- 8858748
TI  - Attenuation of the inflammatory response in an animal colitis model by neutrophil
      inhibitory factor, a novel beta 2-integrin antagonist.
AB  - BACKGROUND: Neutrophils are significant effector cells in acute inflammatory
      bowel disease. Recruitment of these cells is dependent on beta 2-integrin
      mediated adhesion and transmigration. The efficacy of neutrophil inhibitory
      factor (NIF), an antagonist of the beta 2-integrin CD11b/CD18, in ameliorating
      inflammation was tested in an animal model of acute colitis. METHOD: Immune
      complex colitis was induced in groups of rabbits by using various formalin
      concentrations (2%, 0.75%, and 0.5%). Animals were treated with rNIF, 10 mg/kg.
      After they had been killed the mucosal appearance was scored, and tissue saved
      for histology and quantitation of myeloperoxidase (MPO), leukotriene B4 (LTB4),
      prostaglandin E2 (PGE2), and thromboxane B2 (TXB2). RESULTS: In the 2% formalin
      group therapy with rNIF resulted in lower LTB4 (p < 0.05) levels. For the 0.75%
      and 0.5% groups, MPO was lower with rNIF treatment (p < 0.03 and p < 0.05,
      respectively), as were LTB4 concentrations (both, p < 0.04). PGE2 and TXB2 levels
      remained unchanged. Histology showed polymorphonuclear cell infiltration to be
      reduced by rNIF in the 2% and 0.75% formalin-treatment groups (p < 0.05).
      CONCLUSION: These results suggest that blockade of CD11b/CD18-mediated mucosal
      neutrophil recruitment may form part of a strategy for targeted therapeutic
      intervention in inflammatory bowel disease.

PMID- 8858749
TI  - A prospective study of the relationship between disease activity and psychologic
      distress in patients with inflammatory bowel disease.
AB  - BACKGROUND: The evaluation of psychologic states is very useful in the management
      of inflammatory bowel disease (IBD) patients, particularly when related to
      disease activity (DA). Our aim was to prospectively evaluate the relationship
      between psychologic distress and DA. METHODS: DA and psychologic distress were
      evaluated in 104 IBD outpatients by means of clinical criteria and the Hospital
      Anxiety and Depression Scale (HADS) at base line and after 6 months. Patients
      were grouped in unchanged, improved, and worsened DA from base line to follow-up.
      RESULTS: Repeated-measures ANOVA showed a significant group-by-time interaction
      for HADS anxiety (F = 89.6, P = 0.0001) and depression (F = 3.67, P = 0.03)
      subscales. CONCLUSIONS: Over time changes in DA significantly affect psychologic
      distress and are closely related to corresponding increases and decreases in
      anxiety and depression in IBD patients. Our findings therefore suggest that the
      assessment of psychologic distress, particularly anxiety, should be included in
      the clinical management of IBD patients.

PMID- 8858750
TI  - Protective effects of trolox C, vitamin C, and catalase on bromobenzene-induced
      damage to rat hepatocytes.
AB  - BACKGROUND/METHODS: The protective effects of trolox C (water-soluble vitamin E),
      vitamin C, and catalase on bromobenzene (BB)-induced toxicity to isolated rat
      hepatocytes were evaluated. The glutathione (GSH) content of the hepatocytes
      exposed to BB was measured. RESULTS: BB caused acute damage to the cells during 2
      h of incubation (short) when BB was added directly to the culture wells, whereas
      a late-occurring and time-dependent increase in lactate dehydrogenase (LDH)
      leakage rate was observed during 24 h of incubation (long) when BB was dissolved
      in a different way. Incubation of the cells with trolox C (0.5-2.0 mM) prevented
      the hepatocellular damage induced by BB at 2.4 mM during the long-term
      incubation. Vitamin C (0.1-1.0 mM) had a protective effect on BB-induced toxicity
      during both the short- (BB, 1.6 mM) and the long- (BB, 2.4 mM) term incubations.
      Catalase (3200 U/ml) also showed a beneficial effect on the cells during the
      short-term BB exposure. Trolox C (2.0 mM) and vitamin C (0.5 mM) restored BB
      induced GSH depletion in the cells. CONCLUSIONS: BB induced two patterns of LDH
      leakage from isolated hepatocytes on the basis of different ways of BB exposure
      and incubation periods. Trolox C, vitamin C, and catalase exerted protective
      effects on BB-induced toxicity during short- or/and long-term incubations. The
      effects were concentration-dependent. Restoration of GSH content in BB-exposed
      hepatocytes suggests that trolox C and vitamin C could reduce GSH consumption
      during BB metabolism and exert an antioxidant effect.

PMID- 8858751
TI  - Relationship between the serum concentration of 7 alpha-hydroxycholesterol and
      fecal bile acid excretion in humans.
AB  - BACKGROUND: Serum levels of 7 alpha-hydroxycholesterol have been shown to reflect
      the activity of cholesterol 7 alpha-hydroxylase, the key enzyme of bite acid
      synthesis in the liver, but a comparison with direct measurements of bile acid
      synthesis rates has never been performed. METHODS: 7 alpha-Hydroxycholesterol was
      measured by gas-liquid chromatography/mass spectrometry and bile acid synthesis
      by the fecal balance method in 35 subjects. RESULTS: A significant correlation
      was found between 7 alpha-hydroxycholesterol concentration in serum and bile acid
      synthesis (r = 0.863, p < 0.001). Serum levels of 7 alpha-hydroxycholesterol in
      20 patients treated with a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase inhibitor did not differ from levels obtained in healthy volunteers (78
      +/- 7 ng/ml versus 63 +/- 5 ng/ml; NS). Treatment with fenofibrate reduced 7
      alpha-hydroxycholesterol concentrations in six patients from 107 +/- 47 ng/ml to
      61 +/- 12 ng/ml (p < 0.05). CONCLUSIONS: We conclude that the concentration of 7
      alpha-hydroxycholesterol in serum is an indicator of bile acid synthesis and that
      serum levels of 7 alpha-hydroxycholesterol are not affected in patients treated
      with HMG-CoA reductase inhibitors but are affected in those treated with
      fenofibrate.

PMID- 8858752
TI  - Minor role of hepatitis B and C virus infection in the etiology of hepatocellular
      carcinoma in a low-endemic area.
AB  - BACKGROUND: The etiologic role of hepatitis B (HBV) and C virus (HCV) for
      hepatocellular carcinoma (HCC) in a low-endemicity area is obscure. METHODS:
      Patients suspected of having primary liver cancer (PLC) in Goteborg, Sweden (n =
      113), were tested serologically for HBV surface antigen and antibodies to HBV
      surface and core antigens. The presence of HBV surface and core antigens in
      cancer and non-neoplastic liver tissue in HCC cases was investigated
      immunohistochemically. Antibodies to HCV were tested by third-generation tests.
      The prevalence of HBV and HCV infection was compared in 73 patients with HCC and
      32 patients with a final diagnosis other than PLC. RESULTS: No patient had signs
      of chronic HBV infection. Seven of 64 (11%) HCC patients were anti-HCV-positive,
      compared with 1 of 31 (3%) without PLC. All seven patients with HCC and HCV
      infection had liver cirrhosis, and two were alcoholics. Alcoholism was judged the
      commonest (42%) cause of cirrhosis. CONCLUSION: Contrary to areas with a high
      incidence of HCC, chronic viral hepatitis, particularly HBV, seems to play a
      minor etiologic role for HCC in Sweden compared with alcohol-related cirrhosis.

PMID- 8858753
TI  - Serum/ascites albumin gradient: its value as a rational approach to the
      differential diagnosis of ascites.
AB  - BACKGROUND: The utility of differentiating ascites into 'transudate' and
      'exudate' has recently been challenged. The aim of the present study was to
      compare the diagnostic accuracy of the serum/ascites albumin gradient, proposed
      as a new biochemical criterion for the differential diagnosis of ascites, with
      the markers traditionally used for the classification of peritoneal fluid into
      transudate and exudate. METHODS: Paired ascitic fluid and serum samples from 51
      patients were examined with an established method for the diagnosis of the cause
      of ascitic fluid collection. Included in the study were 32 patients with ascites
      related to portal hypertension (cirrhosis, n = 28; 'cardiac' ascites, n = 2; Budd
      Chiari, n = 2) and 19 patients with ascites not related to portal hypertension
      (peritoneal carcinomatosis, n = 17; tuberculous peritonitis, n = I; secondary
      bacterial peritonitis, n = 1). Specimens were collected during an episode of
      spontaneous bacterial peritonitis in 7 of 28 patients with cirrhosis. The
      serum/ascites albumin gradient was compared with ascitic fluid total protein,
      ascites/serum total protein ratio, ascites lactic dehydrogenase concentration,
      and ascites/serum lactic dehydrogenase ratio. RESULTS: The diagnostic accuracy
      was 98% for the serum/ascites albumin gradient compared with only 52%-80% for the
      four other markers tested. In patients with infected ascites, diagnostic accuracy
      was 89% for the albumin gradient and < or = 50% for the four other markers.
      CONCLUSIONS: The classification of ascites into transudate and exudate appears to
      be based on markers with low diagnostic accuracy. Differential diagnosis of
      ascites should be based on the serum/ascites albumin gradient, which is a
      reliable marker distinguishing ascites related to portal hypertension from all
      other causes of ascitic fluid collection, regardless of the presence of bacterial
      infection.

PMID- 8858755
TI  - Hyperplastic polyposis of the large bowel. Three cases and a review of the
      literature.
AB  - Small hyperplastic polyps of the large bowel constitute a frequent non-neoplastic
      lesion, whereas large or multiple hyperplastic polyps are rare. Here we report
      three cases of multiple small polyps together with some large hyperplastic ones.
      Two of the cases had a primary carcinoma in the bowel before onset of the polyps.
      The neoplastic potential of the hyperplastic polyp is discussed on the basis of
      the most recent investigations and the three presented cases. The hyperplastic
      polyp does not seem to be directly involved in the adenoma-carcinoma sequence,
      but dysplastic changes can be found in large hyperplastic polyps. In cases of
      multiple hyperplastic polyps a tendency towards a more uniform distribution of
      the polyps throughout the large bowel is observed. Hyperplastic colonic polyps
      may exist as a clinical entity, and a definition based on distribution,
      multiplicity, size, and symptoms is proposed. Patients with multiple or large
      hyperplastic polyps should have colonoscopy performed at short intervals, with
      removal of all lesions larger than 5 mm for histologic examination.

PMID- 8858754
TI  - Serum trypsinogen-2 in the prediction of outcome in acute necrotizing
      pancreatitis.
AB  - BACKGROUND: The accuracy of serum trypsinogen-2 in predicting the severity of
      acute necrotizing pancreatitis (ANP) was prospectively evaluated in 52
      consecutive patients. METHODS: A new sensitive immunofluorometric assay was used
      for serum trypsinogen-2, RESULTS: Mean values during the first 24 h were 42.1
      micrograms/l in control patients, 1435 micrograms/l in uncomplicated cases, and
      4090 micrograms/l in complicated or fatal cases. There was a significant
      difference in serum trypsinogen-2 values between patients with uncomplicated and
      complicated disease (p = 0.002) already on admission. When a cutoff level of 1000
      micrograms/l was used, patients with uncomplicated ANP were differentiated from
      patients with complicated ANP with a sensitivity of 91% and with a specificity of
      71%. CONCLUSIONS: The immunofluorometric assay of serum trypsinogen-2 is a
      sensitive and specific method for prediction of the severity of the disease in
      necrotizing pancreatitis.

PMID- 8858756
TI  - Controversial aspects in the pathophysiology of duodenal ulcer.

PMID- 8858757
TI  - Continuous quality improvement in the ICU and the role of a data management
      system.
AB  - Quality improvement may be defined as the effort to improve the level of
      performance of key processes in the ICU. Based on knowledge of the current level
      of performance and on systematic analysis of organizational aspects of the ICU,
      quality improvement will include the implementation of standards, the formulation
      and analysis of quality indicators (e.g. scores, rate of complications such as
      nosocomial infections) and the possible introduction of data management systems.

PMID- 8858758
TI  - Should ICU patients receive muscle relaxants?
AB  - Neuromuscular blocking agents (NMBAs) are used in many critically ill patients,
      although their use is declining. NMBAs are designed for short term use in the
      operating theatre, and there are few studies in the critical care setting of
      either efficacy or safety, in particular their metabolism may be impaired by
      organ dysfunction. Weakness associated with critical illness is multifactorial,
      but in many cases is associated with myopathies and neuropathies. The possible
      role of NMBAs in the development of weakness is unclear, but there is no proven
      link between the use of NMBAs and neuropathy or myopathy.

PMID- 8858759
TI  - Molecular biology and the pediatric surgeon: definitions and basic methodology.
AB  - Molecular biology techniques and their application are becoming increasingly
      important to the practicing clinician. This article reviews the basics of DNA
      chemistry and highlights important molecular biology techniques. It will provide
      a guide for the pediatric surgeon as she/he attempts to integrate this field into
      everyday practice.

PMID- 8858760
TI  - cDNA subtraction hybridization: a review and an application to neuroblastoma.
AB  - Recent advances in molecular biological techniques have increased our capability
      to distinguish the small differences in gene expression between subpopulations of
      cells found within specific tissues or tumor isolates. We use subtractive
      hybridization or subtractive cloning to generate information regarding genes that
      direct various aspects of mammalian embryonic development. The technique also is
      used to identify genes with specificity for particular tissues or cell types or
      those that regulate various processes in the cell. Also, subject to analysis is
      the aberrant expression of genes involved in tumorigenesis. Another use is
      analysis of subpopulations of cell types previously identified within individual
      solid tumors. We used subtractive cloning in the analysis of cell line
      subpopulations derived from the human pediatric tumor neuroblastoma. This has
      resulted in the identification of novel genes that may be useful in the study of
      this disease.

PMID- 8858761
TI  - Inflammatory cytokines, nitric oxide, and necrotizing enterocolitis.
AB  - Numerous theories have been proposed to explain the pathogenesis of necrotizing
      enterocolitis (NEC). Current evidence suggests that injury to the intestinal
      barrier as a result of various perinatal insults may facilitate invasion of the
      intestinal wall by bacteria. An inflammatory cascade ensues, characterized by
      local release of various cytokines that may contribute to further tissue
      destruction and hemodynamic instability in NEC. Molecular biological probes show
      increased expression of inducible nitric oxide synthase and interferon-gamma in
      the intestine of infants with NEC. Studies are planned to define the role of
      these inflammatory mediators in a rat model of NEC.

PMID- 8858762
TI  - Nitric oxide and the pulmonary artery smooth muscle cell.
AB  - Nitric oxide (NO) is produced by the enzyme nitric oxide synthase (NOS), which
      exists in different isoforms in various tissues. The inducible NOS (iNOS) isoform
      of the enzyme is expressed in vascular smooth muscle in response to
      lipopolysaccharide and inflammatory mediators. When this expression of iNOS
      occurs in the lung, the NO produced may play a role in the inflammatory process
      of acute lung injury. This article reviews the research that characterizes iNOS
      in rat pulmonary artery smooth muscle and discusses current investigation into
      the role of NO in sepsis and injury.

PMID- 8858763
TI  - The role of the fetal fibroblast and transforming growth factor-beta in a model
      of human fetal wound repair.
AB  - The fetus heals skin wounds without scar formation. Human fetal skin that is
      transplanted to a subcutaneous location on an adult athymic mouse and
      subsequently wounded heals without scar formation, whereas the same fetal skin
      heals with scar formation when transplanted to a cutaneous location. To
      characterize the healing process of human fetal skin in these two locations,
      species-specific human and mouse DNA probes were constructed and used to probe
      graft wounds under high stringency in situ hybridization conditions.
      Immunostaining for species-specific fibroblasts, macrophages, and neutrophils was
      also performed. The cutaneous human fetal graft healed with scar and showed an
      influx of adult mouse fibroblasts and macrophages. In contrast, subcutaneous
      human fetal grafts showed exclusively human fetal fibroblasts in the wound
      environment, an absence of inflammatory cells, and scar-free repair. Thus, the
      highly organized collagen deposition in scarless human fetal wound repair appears
      to be intrinsic to the human fetal fibroblast and occurs in the absence of an
      adult-like inflammatory response. One important cytokine involved in wound repair
      is transforming growth factor-beta (TGF beta). TGF beta promotes inflammatory
      cell recruitment and collagen deposition in healing wounds. To determine the role
      of TGF beta 1 in fetal wound healing, in situ hybridization for TGF beta 1 mRNA
      expression, immunostaining for TGF beta protein, and species-specific
      immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed
      in human adult wounds, fetal wounds, and fetal wounds treated with a TGF beta 1
      slow release disk. TGF beta 1 RNA expression and TGF beta protein were found in
      wounded adult skin. Neither TGF beta 1 mRNA upregulation nor TGF beta protein was
      detected in human fetal skin after wounding. However, when exogenous TGF beta 1
      was added to human fetal skin, induction of TGF beta 1 mRNA expression in human
      fetal fibroblasts occurred, an adult-like inflammatory response was detected, and
      the skin healed with scar formation. Thus, non-scarring fetal skin is relatively
      TGF beta 1 deficient when compared to scarring adult skin. Furthermore, when
      exogenous TGF beta is added to fetal skin, scarring occurs. TGF beta appears to
      be an important modulator in scar formation. With a more thorough understanding
      of scarless repair mechanisms, clinical induction of scarless healing in adults
      and children soon may be possible.

PMID- 8858764
TI  - Molecular and cellular control points in pediatric liver injury and repair.
AB  - Several exciting areas of cellular and molecular biology of the liver have led to
      a better understanding of the mechanisms of pediatric liver injury and repair.
      Soon these advances will lead to treatment options for specialized areas of
      pediatric hepatology. Most of the current goals of surgical therapy lead to
      either successful hepatic resection for tumors or biliary decompression for
      atresia. We have come to accept the unfortunate fact that ongoing chronic liver
      disease ultimately leads to replacement by transplantation. The purpose of this
      article is to demonstrate areas of recent basic science advancement, directly
      related to pediatric liver disease, that may provide opportunities and new
      strategies to obviate the progression from early injury to end-stage liver
      disease or to augment repair of the injured liver.

PMID- 8858765
TI  - Mullerian inhibiting substance as a model for the transforming growth factor-beta
      family: development of new treatment strategies.
AB  - The study of ligand receptor interactions and receptor function often requires
      multifaceted experimental approaches. In the course of studying the function and
      mechanism of action of mullerian inhibiting substance (MIS), we have used a wide
      range of molecular and cellular techniques. These have led to the identification,
      cloning, and characterization of the MIS receptors and of other receptors for the
      transforming growth factor-beta (TGF beta) family. This article describes the use
      of polymerase chain reaction (PCR) cloning to isolate candidate receptor genes,
      transfection and flow cytometry to study ligand binding, nonhomologous
      recombination targeted gene disruption (knockout) to analyze receptor function,
      and yeast genetics to identify other proteins that interact with the receptor
      complex. Together these techniques have led to the development of therapeutics
      and therapeutic strategies that are ready for clinical application.

PMID- 8858766
TI  - Tissue engineering.
AB  - The loss or failure of an organ or tissue is one of the most frequent,
      devastating, and costly problems in health care. Current treatment modalities
      include transplantation of organs, surgical reconstruction, use of mechanical
      devices, or supplementation of metabolic products. Tissue engineering is the
      application of the principles and methods of engineering and the life sciences to
      the fundamental understanding of structure/function relationships in normal and
      pathological tissues and the development of biological substitutes to restore,
      maintain, or improve function. This article discusses the challenges of this
      interdisciplinary field and its attempts to provide solutions to tissue creation
      and repair.

PMID- 8858767
TI  - Gene therapy in pediatric surgery.
AB  - Gene transfer has become a reality during the last decade. The basic principles
      of molecular biology, gene transfer, and the problems associated with this new
      technology have direct implications for the treatment of pediatric surgical
      patients. Research into applications of gene transfer in the treatment of
      disorders of the bone marrow, cancer, hemophilia, hepatic and metabolic disease,
      cystic fibrosis, and vascular disease is rapidly progressing. These areas of
      research may dramatically affect the care of pediatric surgical patients in the
      future.

PMID- 8858768
TI  - Genetic engineering of immunotoxins.
AB  - Immunotoxins, composed of both targeting mechanisms and toxins, hold great
      promise for the treatment of some cancers and other pathological conditions.
      Research and manufacture of these drugs use various techniques of molecular
      biology, some of which are described in this article. A considerable amount of
      research has focused on ricin, a plant toxin, and its immunoconjugates. Areas
      currently under evaluation by our laboratory include structure-function studies
      based on mutational analysis, enhancement of intracellular trafficking, genetic
      fusion of the targeting and toxic moieties, and the expression of toxin in plant
      cell culture.

PMID- 8858769
TI  - Gadolinium-enhanced three-dimensional MR angiography of the thoracoabdominal
      aorta.
AB  - MR angiography (MRA) of the thoracoabdominal aorta is a noninvasive technique
      that can rapidly acquire a volume of data with the capability of multiplaner
      reformations (MPR) and "bright blood" maximum intensity projection (MIP)
      angiographic images. These MIP images can display long tortuous vessels in a
      single three-dimensional (3D) volume, with excellent delineation of branch vessel
      diseases and without the flow artifacts or long examination times of conventional
      spin-echo (SE) imaging. Two-dimensional (2D) time-of-flight (TOF) imaging is used
      most widely because of familiarity and ease of implementation, but this method
      has limitations in evaluating thoracoabdominal aortic disease. Sequential 2D
      axial imaging (which maximizes flow-related enhancement) is time consuming,
      subject to slice-to-slice misregistration, and can be degraded by pulsatile and
      turbulent flow. Coronal or parasagittal imaging is more time efficient, but image
      degradation secondary to in plane saturation and stagnant or turbulent flow from
      aneurysmal disease may lead to nondiagnostic studies. Three-dimensional TOF
      techniques offer the advantages of higher signal-to-noise ratio, better spatial
      resolution with near isotropic voxels, and shorter echo times (TEs), which lessen
      signal loss because of intravoxel phase dispersion. Although these techniques
      provide excellent image quality in the carotid arteries, they are of limited use
      in the aorta because of saturation effects. However, the addition of gadolinium
      chelates shortens the T1 relaxation rate of blood, which obviates the need for
      flow-related enhancement, allowing for inplane imaging without saturation
      effects, even in regions of virtually stagnant flow. The enormous signal
      enhancement of gadolinium chelates enables imaging with high-resolution matrices,
      providing diagnostic angiograms in as little as 2 minutes. With improved
      hardware, faster and stronger gradients, and phased-array coils that increase the
      signal-to-noise ratio, breath-hold gadolinium-enhanced 3D schemes with ultrashort
      TEs will become the optimal method for imaging the aorta and its branch vessels.
      Using this technique, the aorta can be imaged in less than 1 minute.

PMID- 8858771
TI  - Pulmonary MR angiography.
AB  - Recent technical improvements have made pulmonary MR angiography (MRA) feasible.
      The technique is attractive because it is noninvasive, provides a full three
      dimensional (3D) display of the pulmonary vasculature, and potentially can be
      combined with MR venography of the lower extremities and pelvis for the
      comprehensive diagnosis of thromboembolism. Approaches to acquiring pulmonary MR
      angiograms are currently being developed and include both two-dimensional and 3D
      time-of-flight methods, breath-hold and non-breath-hold techniques, and the use
      of gadolinium-based contrast enhancement. The results of initial studies using
      pulmonary MRA for the detection of pulmonary embolism are encouraging, but they
      must be evaluated in conjunction with newly developed fast CT scanning
      techniques. This article reviews the state of development of pulmonary MRA, the
      current clinical applications of the technique, and the prospects for future
      development.

PMID- 8858770
TI  - Spiral CT angiography of the aorta.
AB  - Imaging of the aorta and its branches has benefitted greatly from the development
      of spiral CT techniques, which are relatively fast and noninvasive. The
      volumetric acquisition of spatial information has permitted the computer to
      reformat images for inspection of the vessels by several methods from an infinite
      number of viewing angles. Most aortic diseases-including congenital anomalies,
      dissection, aneurysm, trauma, inflammation, infection, and thromboembolic disease
      can be depicted with this technology. In selected cases, spiral CT may be the
      only imaging modality needed for the surgical planning of aortic repair. This
      report discusses the CT angiography technique, its application to a variety of
      disease states, its role relative to other imaging modalities, and guidelines for
      patient selection.

PMID- 8858772
TI  - Fast CT for pulmonary embolus.
AB  - Recent technical advances in CT have led to the ability to scan a volume in a
      shorter period with optimal contrast opacification of blood vessels, including
      the pulmonary arteries. Initially, there were isolated instances of an accidental
      detection of a filling defect because of pulmonary embolus in the pulmonary
      arteries. Gradually, directed examinations were introduced to diagnose or exclude
      pulmonary embolus. These examinations were successful. Radiologists and
      clinicians now are turning to fast CT for this purpose for a variety of reasons,
      including the proven accuracy and reliability of the method and the relative
      deficiencies of traditional noninvasive methods. Accurate interpretation of CT
      scans for possible pulmonary embolus depends on the ability to conduct a high
      quality examination and to recognize the spectrum of findings for both acute and
      chronic emboli. This article reviews the history of fast CT pulmonary
      angiography, and it presents both technical and diagnostic information germaine
      to the performance of this technique.

PMID- 8858773
TI  - CT angiography of the visceral vessels.
AB  - CT angiography (CTA) is a promising new technique for vascular imaging. This
      review focuses first on the technique necessary for successful scanning of the
      visceral vessels. As in many new modalities, there are different protocols for
      scanning and rendering of images. The relative strengths and weaknesses of these
      different approaches are discussed. A discussion of the applications of CTA to
      depict normal and abnormal anatomy of the visceral vessels follows. These
      applications include celiac stenosis, splenic artery aneurysms, evaluation for
      hepatic arterial anatomy before liver transplantation, visceral arterial anatomy
      in pancreaticoduodenal surgery, the superior mesenteric artery in intestinal
      ischemia, vascular encasement in patients with pancreatic neoplasms, and,
      finally, the hepatic vessels before hepatic tumor resection.

PMID- 8858774
TI  - MR angiography of abdominal ischemia.
AB  - Advances during the past decade in MRI have made this modality increasingly
      suitable for evaluating abdominal vascular diseases. Preliminary results in
      canine models and humans suggest that MRI has the potential of becoming a
      definitive, noninvasive test for the diagnosis of both acute and chronic
      mesenteric ischemia. MRI can provide both morphological information about the
      patency or degree of stenosis in mesenteric vessels as well as quantitative
      functional information such as blood flow and blood oxygen saturation in these
      vessels. The MR techniques developed for studying the mesenteric circulation also
      can be used for improving the diagnosis and posttreatment evaluation of vascular
      diseases in other abdominal organ systems.

PMID- 8858775
TI  - MR angiography of the portal venous system.
AB  - MR angiography (MRA) has become an increasingly important and practical clinical
      tool for the noninvasive assessment of abdominal vessels. Both two-dimensional
      time-of-flight and phase contrast techniques allow accurate evaluation of the
      portal venous system. This article reviews these two MRA techniques and discusses
      their impact on the diagnosis of vascular abnormalities of the portal venous
      system.

PMID- 8858776
TI  - Spiral (helical) CT of the renal vasculature.
AB  - The renal arteries are among the most challenging of the major aortic branches to
      image with spiral CT. Optimization of CT acquisition parameters is critical to
      creating diagnostic renal CT angiograms. When careful attention is paid to
      prescribing these examinations, renal CT angiography can be a very useful,
      noninvasive alternative to conventional angiography for the assessment of renal
      artery stenosis, screening of potential renal donors, planning repair of
      ureteropelvic junction stenoses, and identification of relevant renal artery
      relationships to abdominal aortic lesions. This review outlines important
      technical considerations for performing renal CT angiography and examines
      currently published data on the utility of spiral CT in a variety of clinical
      conditions.

PMID- 8858777
TI  - MR angiography of the renal arteries.
AB  - MR angiography (MRA) has shown considerable promise as a noninvasive tool in the
      evaluation of renal vascular morphology. There are two fundamental approaches to
      MRA of the renal arteries: time of flight and phase contrast imaging. Recently,
      three-dimensional, gradient-echo, gadolinium-enhanced MRA using breath-hold
      techniques also has been introduced. These techniques have made MRA of the renal
      arteries a very promising, noninvasive tool in the detection of main renal artery
      stenosis, with sensitivities between 90% and 100%. MRA is used most often in the
      evaluation of renal arteries of patients with abdominal aortic aneurysms or
      allergies to iodinated contrast media, or when other noninvasive screening
      examinations have been inconclusive. One of the most helpful and unique
      applications of MRA is in patients who have accelerating hypertension and
      accelerating renal insufficiency. These patients often have preexisting
      unilateral renal artery stenosis with a new contralateral renal artery stenosis.
      Conventional angiography is risky in these patients because of possible contrast
      nephropathy. MRA, in such cases, is very helpful for differentiating between
      bilateral renal artery stenosis and end-stage nephrosclerosis.

PMID- 8858778
TI  - MR angiography of the peripheral vasculature.
AB  - MR angiography (MRA) for the evaluation of peripheral arterial occlusive disease
      is a rapidly evolving technique. Recent prospective clinical trials have
      indicated that MRA may play an important role in the evaluation of patients with
      peripheral arterial disease. This article discusses the pertinent technical
      aspects and limitations of peripheral MRA as well as some of the clinical data
      available.

PMID- 8858779
TI  - Toward a more holistic understanding of ethics in social work.
AB  - This paper explores alternative approaches to ethical understanding in social
      work by applying them to a story of a young woman with AIDS. After presenting the
      story, I present four perspectives on ethical discernment: the principles
      approach, virtue ethics, feminist ethics and Afrocentricity. Each approach raises
      different questions and issues regarding the situation. Together they provide a
      more holistic discussion and analysis of social work values, beliefs and ethical
      positions.

PMID- 8858780
TI  - Medicaid eligibility policies for people with AIDS.
AB  - Although Medicaid is the primary payer for health services provided to people
      with AIDS, Medicaid eligibility policies can be restrictive. This study presents
      Medicaid eligibility policies in each state for people with AIDS or HIV
      infection, including the categorical and medically needy classifications. The
      study documents that medically needy coverage is an important route to Medicaid
      coverage for people with AIDS. Because of the importance of this medically needy
      coverage, extending presumptive disability to any person with HIV and allowing
      them to spend down would provide a health financing safety net for people
      infected with HIV.

PMID- 8858781
TI  - Negotiating advance directives for persons with AIDS.
AB  - A focus group was conducted to determine the views of persons with AIDS about how
      to best conduct the process of establishing advance directives. (Advance
      directives are instructions regarding future medical care to be implemented
      should a patient be unable to communicate his/her treatment preferences.) Several
      hypotheses emerged from this focus group that were then formally tested with a
      questionnaire. The results of the questionnaire identified (a) predictors of
      attitudes toward advance directives and (b) predictors of the act of having
      established a directive. Based upon the findings from the focus group and the
      questionnaire, recommendations for social workers raising the issue of advance
      directives can be made. First, time for the client to adjust to seropositive
      notification should be allowed prior to raising the advance directive issue.
      Second, the advance directive issue should be raised in the context of
      empowerment rather than being embedded in other paper work. Third, people who are
      most likely to be disturbed by the process of establishing advance directives are
      those who have low health locus of control, low trait optimism, low reliance on
      active involvement as a coping mechanism, and low reliance on distraction as a
      coping mechanism. More time should be allotted for people with those
      characteristics.

PMID- 8858782
TI  - An empirical study of parents' reaction to the diagnosis of congenital heart
      disease in infants.
AB  - Health care professionals assume that parents of newborn babies diagnosed with
      congenital heart disease experience more negative feelings of sadness, anger,
      fear and guilt than parents of normal newborns. Since there have been no previous
      empirical studies, this study sought to challenge those assumptions. Results of
      the study suggest that parents of such infants were indeed more fearful than
      parents of normal babies. The data also indicates that all parents experience
      sadness, anger and fear, but parents of normal babies experience less anger and
      sadness. Many implications for social work practice, education and research are
      indicated as a result of this study.

PMID- 8858783
TI  - Implementation of computerized social work data base/assessments.
AB  - The Department of Veterans Affairs, Social Work Service has designed, developed
      and implemented the Social Work Information Management System (SWIMS) which
      provides for the collection and reporting of both administrative and clinical
      information. This paper describes the implementation of one component of SWIMS,
      the automated Social Work Data Base/Assessment. The discussion details the
      implementation process and discusses issues encountered in the implementation of
      a computerized documentation system.

PMID- 8858784
TI  - The challenge of practice based research: a group approach.
AB  - Social work research has long been an area overlooked by direct practice
      clinicians for several reasons. Some clinicians are uncomfortable with research
      and tend to avoid it, while others feel they do not have time to generate quality
      research material and still serve clients adequately. The Social Work Services
      Department in a university teaching hospital accepted the challenge of combining
      direct practice and research. By drawing on internal levels of expertise, while
      collaborating with other area professionals, the Research Committee has adopted a
      group approach of individuals conducting practice-based research. This method of
      generating research has yielded many positive results.

PMID- 8858785
TI  - Improved designs for dose escalation studies using pharmacokinetic measurements.
AB  - We describe a method for incorporating pharmacokinetic (PK) data into dose
      escalation clinical trial designs. Doing so can improve the efficiency and
      accuracy of these studies. The method proposed uses a parametric dose response
      function that models the probability of response in each person with two effects:
      the dose of drug administered and an ancillary pharmacokinetic measurements.
      After treatment and observation of each subject (or group of subjects) for
      response, one calculates the dose to be administered to the next individual (or
      group) to yield the target probability of response from the current best estimate
      of the dose-response curve. This procedure is a variant of the continual
      reassessment method (CRM). Statistical simulations employing a logistic dose
      response model (that is, we model the logit of the response probability as a
      linear combination of predictors), dose of drug, and the area under the time
      concentration curve (AUC) demonstrate that the addition of pharmacokinetic
      information to the CRM is a practical and useful way to improve both dose
      response modelling and the design of dose escalation studies.

PMID- 8858786
TI  - Design and analysis of intra-subject variability in cross-over experiments.
AB  - Recently, interest has grown in the development of inferential techniques to
      compare treatment variabilities in the setting of a cross-over experiment. In
      particular, comparison of treatments with respect to intra-subject variability
      has greater interest than has inter-subject variability. We begin with a
      presentation of a general approach for statistical inference within a cross-over
      design. We discuss three different statistical models where model choice depends
      on the design and assumptions about carry-over effects. Each model incorporates t
      variate random subject effects, where t is the number of treatments. We develop
      maximum likelihood (ML) and restricted maximum likelihood (REML) approaches to
      derive parameter estimators and we consider a special case in which closed-form
      expressions for the variance component estimators are available. Finally, we
      illustrate the methodologies with the analysis of data from three examples.

PMID- 8858787
TI  - Estimating population size when duplicates are present.
AB  - Each of K mental health programmes reports the number of patients served in a
      year. The sum of these numbers, y, is an overcount because some patients are seen
      in more than one programme. Health care planners need to know the unduplicated
      number served by the mental health system. Thus, there is an unknown number, M,
      of distinct individuals who appear on one or more of K lists; some appear on
      multiple lists and the duplicates are not readily identifiable. Let X be the
      number of lists on which a randomly selected individual appears. When E(X) is
      known, y/E(X) is the natural estimator of M. We assume that we know the number of
      programmes, Xi, used by the ith individual in a random sample of recipients of
      service. Here, the intuitive estimator, Y/X has desirable statistical properties.
      We give confidence interval estimators for M. We apply the method to estimate the
      number of individuals served in 1991 by the mental health programmes in New York
      State.

PMID- 8858788
TI  - Analysis of multivariate reliability structures and the induced bias in linear
      model estimation.
AB  - Least squares provides consistent estimates of the regression coefficients beta
      in the model E[Y [symbol: see text] x] = beta x when fully accurate measurements
      of x are available. However, in biomedical studies one must frequently substitute
      unreliable measurements X in place of x. This induces bias in the least squares
      coefficient estimates. In the univariate case, the bias manifests itself as a
      shrinkage toward zero, but this result does not generalize. When x is
      multivariate, then there are no predictable relationships between the signs or
      magnitudes of actual and estimated regression coefficients. In this article, we
      characterize the estimation bias, and review a relatively simple adjustment
      procedure to correct it. We also show that several natural conjectures about the
      bias are false. We present three definitions of reliability coefficient matrices
      that generalize the univariate case, and we illustrate their application to
      dietary intake data from a cancer prevention study.

PMID- 8858789
TI  - Simultaneously modelling censored survival data and repeatedly measured
      covariates: a Gibbs sampling approach.
AB  - Recent methodologic developments in the analysis of longitudinal data have
      typically addressed one of two aspects: (i) the modelling of repeated
      measurements of a covariate as a function of time or other covariates, or (ii)
      the modelling of the effect of a covariate on disease risk. In this paper, we
      address both of these issues in a single analysis by modelling a continuous
      covariate over time and simultaneously relating the covariate to disease risk. We
      use the Markov chain Monte Carlo technique of Gibbs sampling to estimate the
      joint posterior distribution of the unknown parameters of the model. Simulation
      studies showed that jointly modelling survival and covariate data reduced bias in
      parameter estimates due to covariate measurement error and informative censoring.
      We illustrate the methodology by application to a data set that consists of
      repeated measurements of the immunologic marker CD4 and times of diagnosis of
      AIDS for a cohort of anti-HIV-1 positive recipients of anti-HIV-1 positive blood
      transfusions. We assume a linear random effects model with subject-specific
      intercepts and slopes and normal errors for the true log and square root CD4
      counts, and a proportional hazards model for AIDS-free survival time expressed as
      a function of current true CD4 value. On the square root scale, the joint
      approach yielded a mean slope for CD4 that was 7 per cent steeper and a log
      relative risk of AIDS that was 35 per cent larger than those obtained by analysis
      of the component sub-models separately.

PMID- 8858790
TI  - A simple method for comparing correlated ROC curves using incomplete data.
AB  - Comparative studies of the accuracy of diagnostic procedures often use a paired
      design to gain in efficiency. Standard methods for analysing data from paired
      designs require complete observations. In many studies, however, one of the test
      results may be missing for some patients. In this paper, we propose a simple
      correction to the existing complete data methods to compare areas under ROC
      curves derived from paired designs. The approach makes it possible to use the
      entire available data set in carrying out the comparison, provided that the
      probability of having both tests does not depend on the test results. As an
      illustration, we apply our method to the analysis of data from prospective
      comparison of MRI and ultrasound in detecting periprostatic invasion.

PMID- 8858791
TI  - Modelling irregularly sampled profiles of non-negative dog triglyceride responses
      under different distributional assumptions.
AB  - General methodology for modelling series of non-negative data observed at
      unequally spaced times is developed. The parameterization enables both the
      importance of the serial association, as well the 'order' of this dependence to
      be expressed. An example is given where the effects of three fibre based diets on
      dog triglyceride profiles are analysed and compared. Many different types of
      models based on common distributions such as the normal, exponential, gamma,
      Weibull and log-normal observations are presented. Comparison of possibly non
      nested models fitted on the same data set is made using the Akaike criterion.

PMID- 8858792
TI  - Trends and strategies for myocardial revascularization.
AB  - Refinements in patient assessment, perioperative management and surgical
      technique have considerably improved the outcome and thus widened the indication
      for coronary bypass surgery. General indications for CABG surgery include left
      main stem stenosis or involvement of the LAD. Currently, there is no optimal
      technique or management, rather an individualized strategy considering the
      individual findings and risks. However, the trend points toward a wider use of
      arterial conduits and avoidance of proximal anastomoses. Recently evolving
      strategies including minimal invasive surgery and transmyocardial laser
      revascularization may indicate the beginning of a new era and show that coronary
      bypass grafting is still an evolving field for cardiac surgeons.

PMID- 8858793
TI  - Improved recovery after cold crystalloid cardioplegia using low-dose glutamate
      enrichment during reperfusion after aortic unclamping: a study in isolated blood
      perfused pig hearts.
AB  - Increased glutamate utilization is a part of the metabolic adaptation to oxygen
      deprivation by the heart. The effect of low-dose L-glutamate (2 mmol/L) during
      continuous reperfusion after aortic unclamping on postcardioplegic recovery was
      studied in pig hearts similar in size, anatomy, and function to the human adult
      heart. After cold crystalloid cardioplegic arrest (CCC) with Bretschneider
      solution no 3, hearts were excised from pigs weighing 70-80 kgs (heart weight,
      average +/- SEM: 308 +/- 4 grams), and reperfused in an isolated blood-perfused
      heart model for 120 minutes. Three groups of hearts were compared. One group of
      hearts was subjected to 30 minutes of CCC only (30 min group; n = 9), another
      group of hearts to 90 minutes of CCC and storage (Control group: n = 16), and a
      third group to 90 minutes of CCC and storage, but with L-glutamate added to the
      blood reperfusate (2 mmol/L) (Glutamate group: n = 18). In the Control group 14
      of 16 hearts (88%) needed electrical defibrillation after start of reperfusion,
      significantly more (p < 0.05) than the 8 of 18 (44%) in the Glutamate group; the
      difference between the 30-min (2 of 9 [22%]) and the Glutamate group was not
      significant (p = 0.48). Developed left-ventricular pressure (DLVP) and positive
      dP/dtmax (+dP/dtmax) was significantly higher in the Glutamate group than in the
      Control group during early reperfusion (DLVP: p < 0.05: +dP/dtmax: p < 0.01) and
      the entire reperfusion (DLVP and +dP/dtmax: p < 0.05), while reperfusion
      responses in the Glutamate and 30-min groups were not significantly different.
      Furthermore, myocardial oxygen uptake was significantly higher in the Glutamate
      group than in the Control group (p < 0.001), but not higher than that in the 30
      min group. Decreased lactate release was found in the Glutamate group compared to
      the Control group during early reperfusion (p < 0.01), and the entire reperfusion
      (p < 0.001). No differences were found between the Control and Glutamate groups
      in alanine exchange. Thus, L-glutamate has a beneficial effect in pig hearts on
      both functional and metabolic recovery after cold crystalloid cardioplegia and
      storage when present in a concentration even as low as 2 mmol/L during continuous
      reperfusion after aortic unclamping. A possible mechanism is a glutamate-induced
      stimulation of the malate-aspartate shuttle leading to increased intramyocardial
      lactate utilization.

PMID- 8858794
TI  - The impact of arterial hypertension on the results of coronary artery bypass
      grafting.
AB  - Arterial hypertension is though to be associated with reduced coronary
      vasodilator reserve in the coronary microcirculation. Increased ventricular mass
      and coronary arteriolar abnormalities are the dominant features in patients with
      severe hypertension, while large-vessel coronary disease is the predominant
      feature in patients with mild hypertension. In the present study we have
      evaluated how hypertension influences the outcome of coronary artery bypass
      grafting (CABG), with emphasis on patients with preoperative left-ventricular
      ejection fraction (LVEF) < or = 25%. Between January 1, 1990 and November 1,
      1994, 77 consecutive patients with LVEF < or = 25% (Hypertensive, n = 38 [group
      I] and normotensive, n = 39 [group II] underwent CABG. During the same time
      period 2289 patients with LVEF > 25% underwent CABG (Hypertensive, n = 870 [group
      III] and normotensive, n = 1419 [group IV]) and were studied for comparison. Mean
      age (64 years), sex distribution (86% men), and other classical risk factors did
      not differ between the groups, except a higher incidence of insulin-dependent
      diabetes in patients with LVEF < or = 25%. There were 18% reoperative CABG, 91%
      of the patients were Canadian Cardiovascular Society's (CCS) angina class 3 and 4
      preoperatively, 38% had unstable angina, and 35% underwent urgent surgery (within
      24 hours of admission). Angiography and operation data did not differ
      significantly between the groups. Hospital mortality in group I was 5.3% and in
      group II 15.4%, p < 0.008. In group III it was 6.3% and in group IV 2.2%, p <
      0.001. Postoperative low cardiac output occurred in 18% (group I) and 39% (group
      II), p < 0.05, and only in 5% in groups III and IV, p < 0.001. Non-fatal
      myocardial infarction and other postoperative complications revealed no group
      differences. LVEF and CCS class improved from 1 month postoperatively in groups I
      and II, however, significantly more in group I (hypertensives), p < 0.001.
      Hypertensive patients with poor left-ventricular function preoperative to were
      found to have a lower hospital mortality and incidence of postoperative low
      cardiac output than normotensiven with LVEF < or = 25%. Hypertensive patients
      also had a better improvement of their left-ventricular function and CCS class
      than normotensiven. Left-ventricular hypertrophy and previous myocardial
      infarction were predictors for mortality in patients with LVEF > 25%. Patients
      with LVEF < or = 25% showed the same tendency, though not statistically
      significant.

PMID- 8858795
TI  - Histomorphological examination of endoluminal stent grafting in the descending
      aorta in a sheep model.
AB  - Experiments were designed to examine the wound healing characteristics at the
      aorta-endograft interface. Thoracic aneurysms were induced in sheep and excluded
      by endovascular placement of a selfexpanding stent graft (Corvita Endovascular
      Graft). After a follow-up of 1, 4, or 12 weeks sheep were sacrificed and the
      corresponding segments of the aorta were subjected to histological examinations.
      Histomorphological evaluation of all groups underlined sufficient exclusion of
      lesions of the aortic wall by endovascular grafting. There was no evidence of
      proximal or distal leakage, graft dislocation or migration. The results appeared
      to be evidence that the endoluminal stent graft may be incorporated by the host
      aortic tissue.

PMID- 8858796
TI  - Spinal cord protection in descending and thoracoabdominal aortic surgery--the
      role of distal perfusion.
AB  - The use of distal perfusion in descending thoracic and thoracoabdominal aortic
      surgery remains a controversial issue. Few mainly retrospective studies which
      directly compare simple clamping with distal perfusion are available. The aim of
      the present study was such a comparison in an own series of descending and
      thoracoabdominal aortic replacement. The records of 29 patients who underwent
      descending or thoracoabdominal aortic replacement between 1988 and 1994 were
      retrospectively reviewed. Patients were divided into two groups. Group I
      consisted of 14 patients who received aortic replacement using simple clamping,
      group II was represented by 15 patients who were operated with distal perfusion
      techniques. In group II left heart bypass with a centrifugal pump was used in 3
      patients, and partial cardiopulmonary bypass with a roller pump in 12 patients.
      The paraplegia/paraparesis rate was 28.6% in group I and 0.0% in group II (p =
      0.0258). There were no statistically significant differences regarding surgical
      revision for bleeding (14.3% in group I, 14.0% in group II), postoperative renal
      failure (14.3% in group I 13.3% in group II), postoperative ventilator dependence
      (9.0 days in group I, 11.2 days in group II), rate of postoperative multisystem
      organ failure (26.7% in group I, 33.3% in group II), length of stay in the ICU
      (13.6 days in group I and 13.9 days in group II), and 30-day mortality (21.4% in
      group I and 33.3% in group II). Methods of distal perfusion in comparison to
      simple clamping can lead to a lower paraplegia/paraparesis rate in descending and
      thoracoabdominal aortic surgery.

PMID- 8858797
TI  - The ex-vivo isolated, perfused human lung model: description and potential
      applications.
AB  - An ex-vivo isolated, perfused, and ventilated human lung (IPHL) model is well
      suited for many kinds of physiological, pharmacological, and surgical studies,
      when the physiological and biochemical conditions in the lung can be maintained
      near to those in vivo. The aim of this work was to develop such a model. The lung
      preparations used were available after resection because of bronchial carcinoma.
      Since the tumor remains intact in these anatomical preparations, this model is
      particularly suitable for investigation of the pharmacokinetics and effects of
      anticancer agents. Carrying out a series of 52 IPHL experiments (with 11 whole
      lung preparations and 41 lobe preparations), we have established an IPHL model
      which allows extracorporeal perfusion and ventilation of the resected lungs in
      physiological conditions for 2-3 hours. The net weight gain during the
      experiment, wet-to-dry weight ratio for lung tissue, angiography of the pulmonary
      artery, pulmonary vascular resistance, color and fluorescence of the lung
      surface, and alveolar gas diffusion into the perfusate proved to be useful
      parameters to assess the stability of the preparations and the quality of the
      experiments. To confirm that an intraparenchymal tumor was perfused via the
      pulmonary artery, methods to detect avidin and dextran-biotin in tumor tissue
      after administration into the perfusion solution were employed. Histological
      examination of bronchial as well as tumor tissue, a computerized
      histoanalyzation, and a tumor grading program demonstrated that IPHL experiments
      did not interfere with the grading and staging of the tumors-an important ethical
      precondition for the use of human preparations in an extracorporeal perfusion
      model.

PMID- 8858798
TI  - Extrathoracic arteriosclerotic vascular changes preclude the use of the internal
      thoracic artery for coronary artery bypass grafting.
AB  - During a two-years period we have treated 6 patients where use of the internal
      thoracic artery for coronary artery grafting was precluded because of
      extrathoracic arteriosclerotic vascular lesions. In four patients with severe
      aorto-iliac occlusive disease preoperative digital angiography demonstrated
      collateralisation of the lower extremity by either the left, right, or both
      internal thoracic arteries (ITA). In these cases use of the ITA was excluded in
      order to preserve the collateral supply and coronary bypass grafting was
      performed using only saphenous vein. In two patients with proximal occlusion of
      the left subclavian artery the right ITA was used as in-situ bypass to graft the
      left anterior descending artery. All patients survived the operation without
      development of a perioperative myocardial infarction, neurological deficit, or
      peripheral ischemia. Although they rarely do, extrathoracic vascular disorders
      can exclude the use of the ITA for grafting. Especially in the case of aorto
      iliac occlusive disease or proximal arteriosclerotic subclavian lesions
      angiographic evaluation is mandatory to prevent the development of life
      threatening peripheral ischemia by harvesting an ITA and to avoid the use of an
      inadequate ITA graft with in-flow occlusion.

PMID- 8858799
TI  - Impaction of foreign body in right coronary ostium.
AB  - This article deals with the impaction of an angiography catheter in the right
      coronary ostium and its subsequent retention as a broken foreign body. The case
      was managed by operative extraction and concomitant CABG. The management of such
      a case is discussed.

PMID- 8858800
TI  - Right-ventricular fibroma presenting as tricuspid stenosis--a case report.
AB  - A male child presented with suspicion of tricuspid stenosis. Echocardiography
      revealed the presence of a mass arising from the free wall of the right ventricle
      and causing right-ventricular inflow obstruction but not involving the tricuspid
      valve. The tumour was excised via right ventriculotomy using cardiopulmonary
      bypass, resulting in survival and a satisfactory clinical course. Histological
      examination showed the tumour to be a fibroma. Tricuspid stenosis is an unusual
      presentation of right ventricular fibroma. Careful examination is essential to
      early diagnosis of cardiac fibromas, particularly in children with unexplained
      cardiac problems. Echocardiography is still a good method for confirmation of the
      diagnosis and for follow-up. In view of the unknown natural history of cardiac
      fibroma, surgical excision should be undertaken. Early detection and prompt
      excision results in immediate and complete relief of symptoms and prolongs the
      life span.

PMID- 8858801
TI  - Left pneumonectomy for a second primary tumor after right upper lobectomy for
      superior sulcus tumor.
AB  - We report on a patient who underwent a left pneumonectomy for a second primary
      lung cancer after a right upper lobectomy and upper chest wall resection for a
      superior sulcus tumor. Although the postoperative course was complicated by
      sputum retention which required a temporary tracheostomy the outcome was good and
      the patient is now living without supplementary oxygen supply. Left pneumonectomy
      may be considered in patients with previous contralateral lobectomy when the
      preoperative evaluation of the patient shows an acceptable predicted
      postoperative pulmonary function. A long-term cure and a good quality of life
      must, however, be offered.

PMID- 8858802
TI  - Tissue and cellular oxygenation state measurement during cardiac surgery.

PMID- 8858803
TI  - Cardiac surgery in Germany during 1995. A report by the German Society for
      Thoracic and Cardiovascular Surgery.

PMID- 8858804
TI  - Quantitative and conceptual contributions of mathematical modeling to current
      views on vitamin A metabolism, biochemistry, and nutrition.

PMID- 8858805
TI  - Mathematical modeling in nutrition: constructing a physiologic compartmental
      model of the dynamics of beta-carotene metabolism.

PMID- 8858806
TI  - Experimental approaches to the study of beta-carotene metabolism: potential of a
      13C tracer approach to modeling beta-carotene kinetics in humans.

PMID- 8858807
TI  - Modeling of folate metabolism.

PMID- 8858808
TI  - Molecular biology in nutrition research: modeling of folate metabolism.
AB  - Model CHO cells obtained by transfecting CHO mutants with the E. coli and human
      folylpolyglutamate synthetase genes have proven useful for assessing the role of
      folylpolyglutamates in one carbon metabolism and for delineating how folate
      intracellular stores are regulated. Cells expressing enzymes in specific
      subcellular compartments, expressing enzymes with different substrate
      specificity's, and expressing enzyme activity at different levels, all in a
      common background, in this case the CHO cell, has allowed the development of
      kinetic models for assessing the role of folypolyglutamate synthetase in folate
      retention and in the cytotoxicity of antifolates.

PMID- 8858809
TI  - Modeling vitamin B6 metabolism.

PMID- 8858810
TI  - Interrelationships between metabolism of glycogen phosphorylase and pyridoxal
      phosphate--implications in McArdle's disease.

PMID- 8858811
TI  - Metabolism of normal and Met30 transthyretin.

PMID- 8858812
TI  - Use of a four parameter logistic equation and parameter sharing to evaluate
      animal responses to graded levels of nitrogen or amino acids.

PMID- 8858813
TI  - Total energy expenditure of free-living humans can be estimated with the doubly
      labeled water method.

PMID- 8858814
TI  - Microdialysis and ultrafiltration.
AB  - Microdialysis and ultrafiltration are complementary sampling techniques that
      facilitate acquisition of data in awake, freely moving animals. Because the
      necessity of blood removal is eliminated, sampling frequency is not limited by
      animal size. The samples obtained by these techniques usually require no
      processing for analysis.

PMID- 8858815
TI  - Membrane vesicles.

PMID- 8858816
TI  - Culture of mammary tissue: glucose transport processes.

PMID- 8858817
TI  - Analysis of bioperiodicity in physiological responses.

PMID- 8858818
TI  - Nutrient-response: a "top down" approach to metabolic control.

PMID- 8858820
TI  - Estimation and use of kinetic parameter distributions in metabolism and
      nutrition.

PMID- 8858819
TI  - Modeling membrane transport.
AB  - Many substrates cross cell membranes by processes other than passive diffusion.
      When the transport is carrier-mediated, e.g., facilitated diffusion, active
      transport, and exchange diffusion, the carrier modifies the conductance of the
      membrane and may either increase or decrease the flux of the substrate across the
      membrane. A common characteristic of all carrier-mediated transport is its
      saturability, as only a finite amount of carrier is available to bind with the
      substrate; even the simplest one-site carrier model exhibits saturation.
      Inclusion of carrier-mediated transport adds additional model parameters that
      describe the transporter. In addition, the model must account for both labeled
      (tracer) and unlabeled (mother) substrate, but this introduces no new parameters.
      There are many possible models for a membrane carrier. The applicability of these
      models must be examined for the specific substrate of interest. Many experiments
      aimed at measuring carrier parameters are carried out on isolated cells or cell
      fragments. Experiments in intact organs (either in vivo and in vitro) are also
      possible. Of particular note is the "bolus sweep" method described by Rickaby et
      al. (1981) and Malcorps et al. (1984). The increasing sophistication of
      experimental procedures, data collection techniques, and computers available to
      investigators continues to extend the depth to which we can probe biological
      systems. With this increased sophistication comes increased costs in time and
      equipment. It behooves us then to extract the maximum amount of information from
      each experimental procedure. Mathematical models assist in doing so, and
      sophistication in model analysis should parallel that in other phases of the
      experiment. Increased realism brings several advantages. Simplification of a
      model to increase its ease of usage and speed in routine data analysis is a
      desirable goal, and comparing a simplified model against a more realistic model
      under the conditions specific to a given experiment is one way to test the
      simplifying assumptions. Additionally, increased model realism can bring new
      insight into unknown aspects of the system. All models, no matter how realistic,
      are always "wrong" in that they are less complex than the real system. Failure of
      the model to explain observed results forces us to further refine the model and
      teaches us something more about the system.

PMID- 8858821
TI  - Dynamic systems and neural networks: modeling in physiology and medicine.

PMID- 8858822
TI  - Graph theoretical methods for physiologically based modeling.

PMID- 8858823
TI  - Immunohistochemical localization of GABA in chameleon retina (Chamaleo Chamaleo).
AB  - We used a policlonal antiserum against GABA and demonstrated GABA
      immunoreactivity (GABA-IR) in several populations of amacrine cells in the inner
      nuclear layer (INL), and other cells in the inner plexiform layer (IPL) of the
      central and peripheral retina of the chameleon. Horizontal cells do not contain
      GABA-IR and the chameleon retina is therefore an exception among non-mammals.
      GABA-IR was not seen in cell bodies in the position of photoreceptor, bipolar and
      interplexiform cells suggesting that GABA is not involved in synaptic
      transmission in the outer plexiform layer of chameleon retina.

PMID- 8858824
TI  - The expression of estrogen receptor and estrogen effect in MBA-15 marrow stromal
      osteoblasts.
AB  - MBA-15, a marrow stromal-derived cell line, was shown to express an estrogen
      receptor. This finding was confirmed by in situ hybridization and receptor
      binding assay. An exposure to estrogen (10(-12)-10(-6) M) in a dose response
      manner resulted in a decrease of cell proliferation as measured by MTT assay.
      Cell function was measured by enzymatic activities of two osteoblastic markers,
      CD10/NEP and alkaline phosphatase. These enzymatic activities were elevated
      following the estrogen treatment. This model enabled direct evaluation of the
      estrogen effect on stromal osteoblast cells.

PMID- 8858825
TI  - Phospholipids and nuclear RNA.
AB  - It has been demonstrated that in hepatocyte nuclei the chromatin phospholipid
      fraction is localized near the RNA in decondensed chromatin. The aim of the
      present study was to see if there is any linkage between phospholipids and other
      nuclear components. Isolated hepatocyte nuclei and nuclear membranes were treated
      with deoxyribonuclease and ribonuclease. No loss of phospholipids was observed
      after DNA digestion, whereas 48% was lost following enzymatic RNA removal. This
      loss of phospholipids, localized either near the membrane or inside the nucleus,
      was not homogeneous for all phospholipids: phosphatidylserine and sphingomyelin
      being the most affected. It can be concluded that 48% of nuclear phospholipids,
      in particular sphingomyelin, is lost with RNA removal. This result is discussed
      in view of a possible role of phospholipids in DNA synthesis and RNA
      transcription.

PMID- 8858826
TI  - Protein retention in the endoplasmic reticulum of insect cells is not compromised
      by baculovirus infection.
AB  - High level expression of the major auxin-binding protein (ABP1) from maize (Zea
      mays L.) has been used to demonstrate that the machinery for retaining proteins
      in the endoplasmic reticulum (ER) of insect cells functions efficiently
      throughout the baculovirus infection cycle. Immunolocalization showed wild-type
      ABP1 (ABP1-KDEL) to be targeted to the lumen of the ER, in accordance with its
      signal peptide and carboxyterminal KDEL ER-retention signal. The protein
      accumulated in dilations of the ER, and none was detected at the cell surface.
      Immunoblotting of concentrated culture medium confirmed that ABP1-KDEL was not
      secreted at a detectable level. In contrast, when the carboxyterminus was mutated
      to KEQL, secretion of the baculovirus-expressed protein was readily detected.
      Immunolocalization and immunoblotting demonstrated that a high proportion of the
      ABP1-KEQL protein was secreted at the cell surface and into the culture medium.
      The data demonstrate that the ER of insect cells has a great capacity to retain
      proteins and that this property is largely unaffected by the cellular disruption
      caused by baculovirus replication.

PMID- 8858827
TI  - Transcellular biosynthesis of cysteinyl leukotrienes by Kupffer cell-hepatocyte
      cooperation in rat liver.
AB  - We previously proposed that an enzymatic cooperation between Kupffer cells and
      hepatocytes may play an important role in cysteinyl leukotriene (LT) production
      in rat liver. An in vitro transcellular synthesis cysteinyl LTs by a Kupffer cell
      hepatocyte coculture system was characterized here. Kupffer cells alone, with
      A23187 stimulation, did not generate cysteinyl LTs until supplemented either with
      isolated hepatocytes or with LTC4 synthase and glutathione, indicating that
      Kupffer cells can synthesize LTA4 but not convert it into LTC4. In contrast,
      hepatocytes converted the LTA4 into cysteinyl LTs and further degraded the
      cysteinyl LTs. Cysteinyl LT production by the Kupffer cell-hapatocyte coculture
      system was optimized by addition of 1-3% serum albumin to the culture and by
      bringing the cell-cell distance closer to less than 3 mu. Tumour necrosis factor
      also stimulated cysteinyl LT production by the coculture system. From these
      results, it is expected that the Kupffer cell-hepatocyte transcellular system for
      cysteinyl LT production actually functions in vivo.

PMID- 8858828
TI  - Insulin produces a biphasic response in Tetrahymena thermophila by stimulating
      cell survival and activating proliferation in two separate concentration
      intervals.
AB  - Cells of Tetrahymena may produce autocrine signal molecules with effects on
      survival and proliferation. Here we have tested the effects of human recombinant
      and bovine insulin, and the B22-B30 fragment of bovine insulin over a wide range
      of concentrations (10(-5)-10(-18) M) on cell survival and proliferation in a
      synthetic nutrient medium. The cells were grown in conical flasks at low initial
      cell densities (40 and 400 cells/ml). Insulin prevented rapid cell death and/or
      promoted cell proliferation over two separate concentration ranges: down to
      nanomolar levels and again in the low pico- and femtomolar range. At an initial
      population density of 400 cells/ml the cells multiplied at both concentration
      intervals. At 40 or fewer organisms/ml the cells multiplied in the high
      concentration interval, whereas in the low interval they survived for about four
      times longer than those in the control cultures. B22-B30 added to cultures of 40
      initial cells/ml produced a stimulation of cell survival in the low pico- and
      high femtomolar range. In the presence of hemin (50 nM) cells at 400 initial
      organisms/ml multiplied at insulin concentrations down to about 3 nM and again
      from 300 am to 10 pM. In some cases, hemin plus insulin activated cell
      proliferation between the two concentration intervals as well. At 40 cells/ml the
      cells not only survived but proliferated in the femtomolar range. Cells in
      cultures supplemented with both hemin and B22-B30 multiplied at the low
      concentration interval (from about 100 fM to 10 pM).

PMID- 8858829
TI  - Characterization of forced suspension culture of spontaneously transformed mouse
      fibroblasts (B-6).
AB  - Mouse fibroblasts (B-6) were cultured on agar-coated dishes. After cells grew for
      2-3 generations relatively rapidly in suspension, they began to grow very slowly
      (stationary phase). Electron microscopic studies showed that cells in a
      stationary phase developed intracellular organella: membranous structures
      (endoplasmic reticulum and Golgi apparatus) became manifest and the number of
      mitochondria increased. The specific activities of succiniccytochrome c reductase
      and 5'-nucleotidase were three and five times higher, respectively, than those of
      cells on the dish.

PMID- 8858830
TI  - Fibrillar arrays of a 110-kDa myosin-like protein in Arabidopsis pistils.

PMID- 8858831
TI  - Remarkable enhancement of antioxidant activity of vitamin C in an artificial
      bilayer by making it lipo-soluble.
AB  - The reaction kinetics between 4-palmitoyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl
      (TEMPO-16) and vitamin C (VC) and its lipophilic derivative ascorbyl-6-palmitate
      (VC-16) was studied by stopped-flow ESR spectroscopy in a synthetic surfactant
      vesicle sodium 1-pentadecyl hexadecyl sulfate (SPHS). TEMPO-16 reacted with VC
      very slowly and showed a biphasic first-order kinetics with rate constants of 9.6
      x 10(-4) and 2.5 x 10(-4) s-1, corresponding to diffusion of TEMPO-16 from the
      external monolayer of SPHS to the bulk water and flip-flop of TEMPO-16 from the
      internal to external monolayer of the vesicle, respectively. On the other hand,
      the reaction of TEMPO-16 with VC-16 was second-order and over three orders of
      magnitude faster than that with VC, presumably due to VC-16 induced fusion of the
      vesicle.

PMID- 8858832
TI  - Effects of novel synthetic sterol probes on enzymes of cholesterol metabolism in
      cell-free and cellular systems.
AB  - A series of novel sterols was synthesised as probes for the enzymatic and
      cellular functions of two important enzymes of intracellular cholesterol
      metabolism, acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol 7 alpha
      hydroxylase. The compounds were 6-fluoro-5-cholesten-3 beta-ol (6
      fluorocholesterol), 7-cholesten-3 beta-ol (7-cholestenol), 6 beta-fluorocholestan
      3 beta-ol (6 beta-fluorocholestanol), 3-acetoxy-6-fluorocholestan-3 beta-ol (3
      acetoxy-6-fluorocholestanol) and 7-methoxy-5-cholesten-3 beta-ol (7
      methoxycholesterol). They were designed to reveal the effect of small changes in
      sterol structure, particularly reactivity of certain parts of the ring structure
      and polarity, on enzyme activity and intracellular cholesterol metabolism. The 3
      beta-hydroxy group was essential for interaction with both enzymes since 3
      acetoxy-6-fluorocholestanol did not affect any of the enzyme-catalysed reactions.
      6-Fluorocholesterol and 7-cholestenol had no effect on cholesterol esterification
      but did inhibit the hydroxylation of cholesterol, as did the other compounds with
      groups that could influence the 7 position, namely 6 beta-fluorocholestanol and 7
      methoxycholesterol. The fluorocholestanols were all competitive substrates for
      cholesterol esterification in cell-free and cellular assays of ACAT activity. 7
      Methoxycholesterol was a surprisingly effective inhibitor of ACAT for a simple
      sterol. However, 6-fluorocholesterol did not have any effect on ACAT, suggesting
      that interactions between the enzyme and the region around C-6 and C-7 of the
      sterol are important. These results show that it is possible to dissect
      components of cholesterol metabolism using simple, specifically substituted
      sterols and thus define a new approach to studying the relationships between the
      various enzymes that catalyse intracellular cholesterol metabolism.

PMID- 8858833
TI  - Mass spectra of tert-butyldimethylsilyl ether derivatives of the major metabolite
      of prostaglandin F.
AB  - The EI mass spectra of four tert-butyldimethylsilyl ether derivatives of the
      major metabolite of prostaglandins F1 alpha and F2 alpha (PGF-M) are presented
      and discussed. Proposed ion assignments and fragmentation pathways are based on
      substituent shifts, on data from a deuterium-labeled methoxime analog, and on the
      analysis of collision-induced dissociation spectra of selected ions. Fragment
      ions suitable for identification and quantification work are proposed.

PMID- 8858834
TI  - Synthesis and antiproliferative activity of cytidine-5'-alkylphosphonophosphates
      and structurally related compounds.
AB  - The chemical synthesis of cytidine-5'-alkyl- and cytidine-5'-alkyl
      (acyl)deoxyglycerophosphonophosphates is reported. The compounds obtained
      represent a novel class of cytostatically active agents based on phospholipids,
      which inhibit the growth of various tumor cell lines in vitro. They are phosphono
      analogs of the cytidine-5'-diphosphate-diacylglycerol (CDP-DAG) possessing a
      structurally modified lipid moiety and a phospholipase C-resistant P-C bond. The
      antiproliferative efficacy of the cytidine-5'-alkylphosphonophosphates strongly
      depends on the alkyl chain length. The cytidine-5'-hexadecylphosphonophosphate
      was found to be the most effective compound tested in this study. Its cytostatic
      effect was distinctly higher than that of the alkyl(acyl) deoxyglycero
      derivatives and of the corresponding diphosphates. The structure of the new
      compounds were confirmed by fast atom bombardment mass spectrometry (FAB). The
      FAB fragmentation pattern is discussed.

PMID- 8858835
TI  - A simple systems approach to neural-immune communication.
AB  - The marine mollusc Aplysia californica is emerging as a useful model system to
      study neuralimmune communication at the mechanistic level because it has a well
      characterized nervous system that is easily accessible and it shares with mammals
      similar basic cellular defensive responses to wounded or non-self, i.e. the
      accumulation of defense cells (haemocytes) at the target site. Loose ligation of
      peripheral nerves in Aplysia induces a cellular defense response as evidenced by
      the accumulation of numerous haemocytes around the ligature. The excitability of
      nociceptive sensory neurons having axons close to the responding haemocytes is
      significantly increased. Haemocytes also accumulate at regions of axonal injury.
      The finding that human recombinant IL-1 beta can enhance the expression of injury
      induced sensory hyperexcitability coupled with the detection of (ir)IL-1 in
      Aplysia haemolymph raises the interesting possibility that cytokines released
      from activated haemocytes attracted to an injured nerve or to a foreign body
      close to peripheral nerves may modulate nociceptive sensory function. The
      feasibility of using results from simple system such as Aplysia to formulate
      testable hypotheses in more complex systems is also discussed.

PMID- 8858836
TI  - Crossreactivity of hemolytic and hemagglutinating proteins in the coelomic fluid
      of lumbricidae (Annelida).
AB  - Oligospecific antisera against the hemolytic and hemagglutinating compounds of
      the coelomic fluid (CF) of the earthworm species Eisenia fetida, Lumbricus
      terrestris and Aporrectodea caliginosa were prepared. The proteins were bound to
      the membranes of erythrocytes and injected into rabbits. By the use of these
      antisera the following results were obtained: 1) The antisera RaL T and RaAC
      reached a titer of 1:64,000, the detection limit of RaEF was 1:512,000. RaEF was
      demonstrated to be oligospecific only against three hemolytic proteins by Western
      blotting. 2) RaEF is able to inhibit the biological activity not only of
      hemolysins (E. fetida, A. caliginosa) but also of hemagglutinins (L. terrestris,
      L. rubellus, D. rubidus). 3) Complex carbohydrates, but not simple sugar
      compounds, are able to inhibit hemolytic and agglutinating activities in the CF
      of the investigated species. Fet. and alpha 1ac. GP were demonstrated to be
      strong inhibitors both of the hemolytic and of the hemagglutinating activity,
      whereas N-acetylglucosamine was only able to inhibit the hemagglutinating
      activity. 4) The investigated compounds were shown to crossreact in ELISA
      experiments. 5) By the use of Western blotting, the crossreacting molecules in
      the CF of the investigated lumbricid species were identified.

PMID- 8858837
TI  - The role of glucocorticoids in the growth of the digestive tract in mink (Mustela
      vison).
AB  - The effect of glucocorticoids on the growth of digestive organs was investigated
      in the postnatal period of mink. A total of 110 mink kits from 20 litters were
      either not injected or injected intramuscularly for seven days with saline,
      adrenocorticotropic hormone (ACTH, 50 micrograms/kg/day) or hydrocortisone
      acetate (synthetic glucocorticoid, 50 mg/kg/day). The kits were killed at 2-10
      weeks of age. Plasma cortisol levels did not change significantly with age in the
      control animals. In the ACTH group, plasma cortisol was minimum at 4 weeks of
      age, whereas in the hydrocortisone-acetate group, plasma cortisol was maximum at
      this age. The mink appears to have a period of reduced adrenal responsiveness to
      ACTH and a low metabolic clearance rate of cortisol around 4 weeks of age. The
      weight of the ventricle, pancreas and intestine per body weight reached a maximum
      at 6-8 weeks of age. Hydrocortisone-acetate treated kits showed reduced body
      growth at 2-6 weeks and increased weight of the pancreas and intestine at 6-10
      weeks. The postnatal growth of digestive organs was relatively slow in mink kits
      and the effects of exogenous cortisol administration occurred relatively late in
      mink compared with some other species (rats, pigs). Cortisol may play a
      regulatory role in the growth of digestive organs in the postnatal period of mink
      kits.

PMID- 8858838
TI  - Ca2+ and Cl(-)-dependence of the turtle olfactory response to odorants and
      forskolin.
AB  - In the turtle olfactory system, large responses to odorants appeared after
      application of cAMP of forskolin at high concentrations to the isolated olfactory
      receptor neurons or the olfactory epithelium, suggesting that a cAMP-independent
      pathway greatly contributes to the generation of odor responses. We measured the
      effects of the mucosal Ca2+ and Cl- concentrations and a Ca(2+)-activated Cl(-)
      channel blocker, 4-acetamide-4'-(isothiocyano) stilbene-2,2'-disulphonic acid
      (SITS), upon olfactory bulbar responses to explore the contribution of the Ca(2+)
      activated Cl(-)-channels to cAMP-dependent and independent pathways. Elimination
      of mucosal Ca2+ by addition of 2 mM EGTA to the stimulating solution partially
      inhibited the cAMP-independent responses to 0.1 mM citralva but did not affect
      those to 0.1 mM lilial or 0.1 mM l-carvone. Substitution of mucosal Cl- with
      gluconate slightly enhanced the total response to 0.1 mM citralva but practically
      did not affect the responses to other odorants tested. SITS (2 mM) partially
      inhibited the responses to 50 microM forskolin and 0.1 mM citralva but did not
      affect the cAMP-independent response to 0.1 mM citralva in Ca(2+)-free Ringer's
      solution. These results suggested that the Ca(2+)-activated Cl- channels do not
      contribute to the generation of the cAMP-independent responses, but that they
      partially contribute to the generation of the cAMP-dependent responses in the
      turtle.

PMID- 8858839
TI  - Quantitative urinary excretion of unmetabolised N tau-[Me-14C] methylhistidine by
      the common ringtail possum (Pseudocheirus peregrinus) marsupialia.
AB  - Six common ringtail possums (Pseudocheirus peregrinus) were intravenously
      injected with a standard dose of radioactive 3-Methylhistidine (N tau-[Me
      14C]MeH). The dose was rapidly and quantitatively excreted by the possums. More
      than 90% of radioactivity was recovered within 3 days. Thin layer chromatography
      and mass spectroscopy showed that 97% of recovered radioactivity was associated
      with unmetabolised N tau-[Me-14C]MeH. These data satisfy two key requirements for
      the validity of urinary 3-Methylhistidine (N tau-3MeH) excretion as an index of
      muscle protein catabolism, in P. peregrinus.

PMID- 8858840
TI  - Inhibitory effects of short intravascular infusions of propionate on reticulo
      rumen motility in the sheep.
AB  - The effect of short infusions into the hepatic portal vein of propionate on
      reticulo-rumen motility was examined in conscious sheep. Infusions of 10 min
      duration of propionate at 1-6 mmol.min-1 into the portal vein reduced the
      frequency and amplitude of reticulum and rumen contractions, especially the
      amplitude of rumen contractions. Inhibitory effects were not confined to the
      portal route and were also obtained via the jugular vein, carotid artery, coeliac
      artery and anterior mesenteric artery. Butyrate was also effective, but acetate
      much less so and NaCl almost without effect. The inhibitory responses remained
      after section of nerves to the liver. It appears unlikely the effects reflexly
      originate from the liver or are derived centrally.

PMID- 8858841
TI  - Lithium transport in the chicken and marine teleost kidney.
AB  - The clearance ratio-C(Li)/C(ln) (Excretion Fraction of Lithium-EFLi) in the cod
      (Gadus morrhua L.) kidney amounts to 15.1 +/- 4.7, in the black sculpin
      (Myoxocephalus scorpius L.) kidney, to 6.88 +/- 1.22, which indicates secretion
      of lithium by the marine teleost kidney. A direct correlation has been found
      between EFLi and EFMg. Injection of furosemide (15 mg/kg B.W.) increase while
      injection of the 20% para-amino-hippurate solution (1.6 ml/kg B.W.) does not
      change EFLi in the cod kidney. Infusion of 10 mM LiNO3 in the 0.9% NaCl solution
      (3.5 ml/kg B.W.) into the chicken (Gallus domesticus L.) left v. saphena
      produces, owing to the lithium inflow into the renoportal system, a marked
      unilateral increase of the renal lithium excretion. Infusion of 10% NaCl solution
      (3.5 ml/kg B.W.) together with 10 mM LiNO3 into the chicken left v. saphena is
      accompanied by a more pronounced ipsilateral increase of the lithium excretion
      and EFLi. The data obtained indicate diversity of mechanisms (glomerular
      filtration, reabsorption and secretion) participating in the renal lithium
      excretion in the animals studied.

PMID- 8858842
TI  - Influence of dietary fiber consumption on oxidative metabolism and anaplerotic
      flux in isolated rat colonocytes.
AB  - Colonic fermentation of dietary fiber produces short-chain fatty acids which are
      energetic substrates for colonocytes. A high-fiber diet may lead to adaptations
      in colonocyte energy utilization, product formation and anaplerotic fluxes. For 2
      weeks, Sprague-Dawley rats consumed diets containing 0, 150 or 300 g/kg fiber in
      place of digestible carbohydrate. Colonocytes were isolated; substrate oxidation
      and anaplerotic flux were measured. Glutamine oxidation was higher and glutamate
      formation was lower with increasing levels of fiber. Glucose, propionate and
      butyrate oxidation were not altered by diet. ATP yield from glutamine was higher
      in fiber-fed rats, but ATP from propionate, butyrate and glucose were not
      affected by the diets. Assessment of anaplerotic flux using the CO2 ratios method
      revealed no changes attributable to diet. The amount by which CO2 production is
      greater from C-1 vs C-2 of short-chain fatty acids in this system was established
      to be approximately 2-fold. Colonocytes use fuels in the preferential order of:
      glucose & butyrate > > propionate & glutamine. Because differences attributable
      to diet do not lead to physiologically significant alterations in anaplerotic
      flux or ATP yield, only minor adaptations of colonocyte oxidative metabolism
      occur after 2 weeks of consuming a high fiber diet.

PMID- 8858843
TI  - Comparative electrophoretic investigation of Rana temporaria, R. graeca and R.
      dalmatina.
AB  - The results of comparative electrophoretic analysis on muscle esterases,
      superoxide dismutases, lactate dehydrogenases, malate dehydrogenases-NAD
      dependent, phosphoglucomutases and myogens in the brown frogs Rana temporaria, R.
      graeca and R. dalmatina are described. The coefficient of similarity and indices
      of divergence among the species investigated were estimated. It was established
      that in relation to the protein systems analysed R. graeca differed more
      significantly from R. dalmatina than from R. temporaria. It is suggested that the
      higher electrophoretic similarity of R. temporaria and R. dalmatina is a result
      of a greater divergence of the latter in comparison with R. graeca.

PMID- 8858844
TI  - Liquid conservation in orangutans (Pongo pygmaeus) and humans (Homo sapiens):
      individual differences and perceptual strategies.
AB  - Four orangutans (1 juvenile, 2 subadults, and 1 adult) and ten 6-8-year-old
      children were tested in 4 liquid conservation tasks of increasing levels of
      difficulty. Task difficulty depended on the type of transformation (continuous
      vs. discontinuous quantities) and the relative contrast between the shapes of the
      containers. Results indicate that orangutans did not display conservation in the
      strict sense; instead they showed "partial" conservation (intermediate reactions
      according to J. Piaget & B. Inhelder, 1941). In contrast, some of the children
      provided evidence of conservation in all 4 tasks, showing "true" or logically
      necessary conservation in the original sense proposed by J. Piaget and B.
      Inhelder (1941). Although orangutans did not show conservation in the strict
      sense, as J. Piaget (1955) and others have generally agreed it should be defined,
      orangutans behaved as individual and creative problem solvers, adopting different
      perceptual strategies depending on the task.

PMID- 8858845
TI  - Type of prenatal sensory experience affects prenatal auditory learning in
      bobwhite quail (Colinus virginianus).
AB  - This study examined the effects of specific types of prenatal auditory
      stimulation on the auditory learning capacity of bobwhite embryos (Colinus
      virginianus) incubated in either communal or isolation conditions. Results
      revealed that socially incubated embryos could learn an individual bobwhite
      maternal call, whereas embryos denied physical and tactile stimulation as a
      result of isolation incubation failed to demonstrate prenatal auditory learning
      of the maternal call. In contrast, embryos exposed to bobwhite chick contentment
      calls in the period prior to hatching demonstrated prenatal auditory learning,
      whether they were incubated socially or in isolation. Socially incubated and
      isolation-incubated embryos exposed to bobwhite chick distress calls failed to
      learn the individual maternal call, indicating that the type of sensory
      stimulation the developing organism encounters prenatally is important in
      fostering normal perceptual learning ability.

PMID- 8858846
TI  - Kinship and familiarity as factors affecting social transfer of food preferences
      in adult Mongolian gerbils (Meriones unguiculatus).
AB  - Experiments were carried out with Mongolian gerbils (Meriones unguiculatus) to
      assess whether a socially mediated acquisition of diet selection exists in this
      species. Results showed that a gerbil was influenced in its diet choices by
      information extracted during a brief period of interaction with a familiar
      conspecific that had recently eaten a novel food. Data revealed that the
      acquisition of a food preference from a conspecific depends on the existence of a
      social bond between the interacting gerbils. Either genetic relatedness (being
      brother or sister raised in different litters) or familiarity (being bred in the
      same litter or being member of a reproductive pair) is necessary for the transfer
      of information. Unfamiliar and unrelated observer gerbils did not selectively
      choose their demonstrator's food.

PMID- 8858847
TI  - A gene correlate of geotaxis near Adh (2-50.1) in Drosophila melanogaster.
AB  - As part of a long-term study (38+ years) to identify genetic correlates of
      geotaxis in Drosophila melanogaster, the investigators report the results of
      allozyme-level analyses of 2 lines derived from hybridizing high- and low
      selected lines that have evolved stable, extreme expressions of geotaxis. Allelic
      variation at Adh was associated with geotactic performance in 1 hybrid-derived
      line, but not in another, after 66 free-mating generations beyond the F2
      generation. A second-chromosome gene correlate of geotaxis may lie within 1 map
      unit of Adh. Population genetic analyses suggest that there were different
      selection pressures on the hybrid-derived lines and that the fixation of PGD-A in
      the high-geotaxis line was probably due to a founder-effect event.

PMID- 8858848
TI  - Effect of avian-human joint attention on allospecific vocal learning by grey
      parrots (Psittacus erithacus).
AB  - The authors studied whether grey parrots (Psittacus erithacus) would learn
      referential English vocalizations if training lacked full social interaction with
      humans. In previous studies, grey parrots learned human vocalizations most
      readily when training simultaneously demonstrated the meaning (full reference)
      and function (full contextual applicability) of the utterance and actively
      engaged the subject in learning (full interaction). Those studies, however, did
      not contrast effects of limited and full interaction or examine how interaction
      affects contextual applicability. Because an important factor in child language
      acquisition is joint attention-the social interaction between caretaker and human
      infant concerning objects and actions in their environment-the authors contrasted
      training in which joint attention was present or absent (i.e., full vs. limited
      interaction) and found that 2 parrots did not learn in the absence of joint
      attention but did learn English labels when full interaction was present.

PMID- 8858849
TI  - A kinematic analysis of evasive dodging movements used during food protection in
      the rat (Rattus norvegicus): evidence for sex differences in movement.
AB  - Food-deprived rats (Rattus norvegicus) will protect their food by dodging away
      from a conspecific. A detailed kinematic analysis of these movements in adult
      rats shows that each sex uses sex-typical movements. Females move their snout
      through a greater spatial curvature, and their snout achieves a greater velocity,
      relative to the pelvis, than males. Males make more hindpaw steps than females
      and achieve a more simultaneous movement of the fore- and hindquarters. This
      suggests that females pivot around a point more posterior on the body than males.
      The finding that functionally similar patterns of movement have a sex-specific
      organization provides a new dimension for the study of sex differences. These
      differences are discussed in relation to sex differences in sex-typical
      behaviors, associated body structure, and neural control.

PMID- 8858850
TI  - Shift of laterality and compared analysis of paw performances in cats during
      practice of a visuomotor task.
AB  - Paw preference and performance were analyzed during early and late practice in 12
      adult cats that reached toward a moving target. A strong preference for left-paw
      use was observed early in training. It was still present after practice despite a
      shift toward right-paw use. Comparing paw performance showed that the left paw
      was more accurate and quicker to trigger the movement during early practice,
      whereas after practice, it was the preferred paw (whether right or left) that
      triggered faster movement. The strong original left-paw bias could reflect the
      specialization of the right hemisphere in processing spatial information. Its
      weakening with practice could reflect the ability of the nonspecialized
      hemisphere to learn how to deal with the task.

PMID- 8858851
TI  - Imitative learning in male Japanese quail (Coturnix japonica) using the two
      action method.
AB  - The study of imitative learning in animals has suffered from the presence of a
      number of confounding motivational and attentional factors (e.g., social
      facilitation and stimulus enhancement). The two-action method avoids these
      problems by exposing observers to demonstrators performing a response (e.g.,
      operating a treadle) using 1 of 2 distinctive topographies (e.g., by pecking or
      by stepping). Japanese quail (Coturnix japonica) observers exposed to conspecific
      demonstrators showed a high correlation between the topography of the response
      they observed and the response they performed. These data provide strong evidence
      for the existence of true imitative learning in an active, precocious bird under
      conditions that control for alternative accounts.

PMID- 8858852
TI  - Selecting a common direction. II. Peak-like solutions representing total
      alignment of cell clusters.
AB  - The problem of alignment of cells (or other objects) that interact in an angle
      dependent way was described in Mogilner and Edelstein-Keshet (1995). In this
      sequel we consider in detail a special limiting case of nearly complete
      alignment. This occurs when the rotational diffusion of individual objects
      becomes very slow. In this case, the motion of the objects is essentially
      deterministic, and the individuals or objects tend to gather in clusters at
      various orientations. (Numerical solutions show that the angular distribution
      develops sharp peaks at various discrete orientations.) To understand the
      behaviour of the deterministic models with analytic tools, we represent the
      distribution as a number of delta-like peaks. This approximation of a true
      solution by a set of (infinitely sharp) peaks will be referred to as the peak
      ansatz. For weak but nonzero angular diffusion, the peaks are smoothed out. The
      analysis of this case leads to a singular perturbation problem which we
      investigate. We briefly discuss other applications of similar techniques.

PMID- 8858853
TI  - Large-sample analysis for a stochastic epidemic model and its parameter
      estimators.
AB  - This paper considers the simplest stochastic model for the spread of an epidemic
      in a closed, homogeneously mixing population. Approximate methods are presented
      for calculating the probability distribution of the epidemic size (i.e. number of
      infected individuals). In fact, a functional central limit theorem and a large
      deviation principle for the epidemic size when the population increases are
      shown. These results enable us to both obtain a global approximation for the
      epidemic size and study asymptotic properties of other random variables depending
      on the complete history of the epidemic. As an application of our results, we
      derive two sequences of estimators for the contact rate and analyze their
      asymptotic behaviour.

PMID- 8858854
TI  - A model for predicting the transmission rate of malaria from serological data.
AB  - A model is developed to estimate the duration for which malaria antibody levels
      in the blood remain high in a closed population. This estimate can be used to
      calculate the transmission rate within a region, in conjunction with the
      serological information contained in the population. The model is used on data
      obtained from a study of malaria in the Philippines and shows excellent
      agreement. It is subsequently utilised for predictions and seems to be an
      appropriate vehicle for this purpose.

PMID- 8858855
TI  - Compatibility and the genesis of residual stress by volumetric growth.
AB  - The equations of compatibility which are pertinant for growth strain fields are
      collected and examples are given in simply-connected and multiply-connected
      regions. Compatibility conditions for infinitesimal strains are well known and
      the possibilities of Volterra dislocations in multiply-connected regions are
      enumerated. For finite growth strains in a multiply-connected regions, each case
      must be examined individually and no generalizations in terms of Volterra
      dislocations are available. Any incompatible growth strains give rise to residual
      stresses which are known to occur in many tissues such as the heart, arterial
      wall, and solid tumors.

PMID- 8858856
TI  - On an interacting particle system modeling an epidemic.
AB  - We consider an interacting particle system on Zd to model an epidemic. Each site
      of Zd can be in either one of three states: empty, healthy or infected. Healthy
      and infected individuals give birth at different rates to healthy individuals on
      empty sites. Healthy individuals get infected by infected individuals. Infected
      and healthy individuals die at different rates. We prove that in dimension 1 and
      with nearest-neighbor interactions the epidemic may persist forever if and only
      if the rate at which infected individuals give birth to healthy individuals is
      high enough. This is in sharp contrast with models analysed by Andjel and
      Schinazi (1994) and Sato et al. (1994) where infected individuals do not give
      birth. We also show that some results in the latter reference can be obtained
      easily and rigorously using probabilistic coupling to the contact process.

PMID- 8858857
TI  - Two-photon excited lifetime imaging of autofluorescence in cells during UVA and
      NIR photostress.
AB  - By monitoring coenzyme autofluorescence modifications, as an indicator of cell
      damage, the cellular response to femtosecond near-infrared (NIR) radiation (two
      photon absorption) was compared with exposure to low-power UVA radiation (one
      photon absorption). Excitation radiation from a tunable Ti-sapphire laser,
      focused through high-numerical-aperture microscope optics, provided diffraction
      limited microbeams of an adjustable peak power. Laser scanning NIR microscopy was
      used to detect spatially the intracellular distribution of fluorescent coenzymes
      by fluorescence intensity imaging as well as fluorescence lifetime imaging (tau
      mapping). Upon the onset of UV or NIR exposure, Chinese hamster ovary cells
      exhibited blue/green autofluorescence with a mean lifetime of 2.2 ns, which was
      attributed to NAD(P)H in mitochondria. Exposure to 365 nm radiation from a high
      pressure mercury lamp (1 mW, 300 J cm-2) resulted in oxidative stress correlated
      with increased autofluorescence intensity, onset of nuclear fluorescence, and a
      fluorescence lifetime decrease. The cellular response to femtosecond NIR
      microbeams depended significantly on peak power. Peak powers above a threshold
      value of about 0.5 kW (average power: 6 mW). 0.55 kW (7 mW) and 0.8 kW (10 mW) at
      730 nm, 760 nm and 800 nm, respectively, resulted in the onset of short-lived
      luminescence with higher intensity (100 x) than the intracellular NAD(P)H
      fluorescence. This luminescence, accompanied by destruction of cellular
      morphology, was localized and occurred in the mitochondrial region. In contrast,
      beams at a power of less than 0.5 kW allowed nondestructive fluorophore detection
      with high spatial and temporal resolution without modification of cellular redox
      state or cell morphology.

PMID- 8858858
TI  - New polyacrylamide gel-based methods of sample preparation for optical
      microscopy: immobilization of DNA molecules for optical mapping.
AB  - New methods have been developed for rapid immobilization of biological
      macromolecules and other microscopic objects from aqueous solution at gel/gel,
      gel/solid and gel/solution interfaces using thin polyacrylamide gels covalently
      bound to glass surfaces. When quickly spread over a dry gel, an aqueous sample
      loses most of its water and low-molecular-weight solutes due to migration of
      these components into the gel. All optically observable objects thus become
      concentrated at the gel surface and may be easily located by light microscopy.
      Based on this, a procedure for binding DNA at a positively charged gel/solution
      interface was developed. A mild immobilization of the DNA molecules was obtained,
      allowing 'all in focus' observations of DNA digestion by restriction
      endonucleases with an apparent rate close to that in solution.

PMID- 8858859
TI  - Application of confocal scanning laser microscopy for an automated nuclear
      grading of prostate lesions in three dimensions.
AB  - Confocal scanning laser microscopy provides the opportunity to obtain three
      dimensional (3-D) images by piling up consecutive confocal planes. This technique
      was applied to capture 3-D images from 100-microns-thick tissue blocks from
      prostate lesions (hyperplasia, dysplasia, adenocarcinomas). Automated methods
      were implemented to perform a nuclear grading of 3-D cell nuclei from these
      specimens. Special attention was focused on the development of a new approach to
      3-D chromatin texture analysis. This method uses mathematical morphology
      operations to tessellate the chromatin into homogeneous domains. The nuclear
      features (volume, shape, texture) were subjected to a discriminant analysis.
      Using a set of five features, the classification of cell nuclei yielded an
      accuracy of 96.3%. The results indicate the potential of 3-D imaging and analysis
      techniques for an automated nuclear grading of prostate lesions.

PMID- 8858860
TI  - Automated recognition and mapping of immunolabelled neurons in the developing
      brain.
AB  - The cerebral cortex is distinguished by layers of neurons of different
      morphologies and densities. The layers are formed by the migration of newly
      generated neurons from the ventricular zone to the cortical plate near the outer
      (pial) boundary of the cortex, along radial paths approximately perpendicular to
      the cortical surface. Immunochemical labelling makes these cells' patterns
      visible in brightfield microscopy so that layer formation can be studied. We
      developed a suite of programs that automatically digitize the entire cortex,
      identify the labelled cells and compute cell densities along local radial paths.
      Cell identification used supervised classification on all the significantly
      stained objects corresponding to maxima in lowpass filtered versions of the
      digital microgrphs. Classification of all the stained objects as cells or noncell
      objects was made by a decision rule based on morphometric and grey-level texture
      features, including features based on Gabor functions. Detection sensitivity and
      classification accuracy were jointly maximized on training data consisting of
      about 3000 expert-identified neurons in micrographs. Total program performance
      was tested on a separate (test) set of labelled neurons the same size as the
      training data set. The program detected 85% of the cells in the test set with a
      total error of 0.19. The identified cells' locations were used to compute
      population densities along normals to the cortical layers, and these densities
      served as a measure of neuronal migration. Transcortical density profiles
      obtained by computation and by manual cell counting were very similar. The cell
      identification program was built on well-established methods in statistical
      pattern recognition and image analysis and should generalize readily to other
      histological preparations.

PMID- 8858861
TI  - A new gene, aadA2b, encoding an aminoglycoside adenylyltransferase, AAD(3")(9),
      isolated from integron InC in Pseudomonas aeruginosa.
AB  - A gene, designated aadA2 and encoding an aminoglycoside-adenylyltransferase, was
      located on integron InC, isolated from the R-plasmid of Pseudomonas aeruginosa,
      as a gene cassette. The aadA2 gene of InC was identical to those of pSa and R1033
      with the exception of one base in each case. This single-base substitution did
      not influence the expression of streptomycin resistance. It is proposed that the
      aadA2 genes isolated from pSa and from R1033, and the aadA2 gene from InC, be
      designated aadA2a and aadA2b, respectively.

PMID- 8858862
TI  - Effects of nutrient media and culture duration on growth, macromolecular
      composition and toxicity in batch cultures of Microcystis aeruginosa.
AB  - The effects of media and culture duration on growth, macromolecular composition
      and toxicity of the freshwater cyanobacterium Microcystis aeruginosa were
      evaluated. Four media (MA, CB, A3M7 and BG-11) influenced growth in terms of cell
      numbers, chlorophyll a content and specific growth rate. MA medium supported the
      best growth. The macromolecular composition of cultured cells, viz total protein,
      carbohydrates, lipids, DNA and RNA content, varied reaching a maximum at various
      growth periods. The differences were significant due to the interaction of the
      culture medium and duration. Toxicity was compared in terms of mouse units. The
      toxicity of cultured cells increased with the duration until week 4 and toxicity
      was highest in cells grown in MA medium.

PMID- 8858863
TI  - Biofilms associated with poultry processing equipment.
AB  - Aerobic and Gram-negative bacteria were enumerated on non-metallic surfaces and
      stainless steel test pieces attached to equipment surfaces by swabbing and a
      mechanical dislodging procedure, respectively, in a South African grade B poultry
      processing plant. Changes in bacterial numbers were also monitored over time on
      metal test pieces. The highest bacterial counts were obtained from non-metallic
      surfaces such as rubber fingered pluckers and plastic defeathering curtains which
      exceeded the highest counts found on the metal surfaces by at least 1 log CFU cm
      2. Gram-negative bacterial counts on all non-metallic surface types were at least
      2 log CFU cm-2 lower than corresponding aerobic plate counts. On metal surfaces,
      the highest microbial numbers were obtained after 14 days exposure, with aerobic
      plate counts ranging from 3.57 log CFU cm-2 to 5.13 log CFU cm-2, and Gram
      negative counts from 0.70 log CFU cm-2 to 3.31 log CFU cm-2. Scanning electron
      microscopy confirmed the presence of bacterial cells on non-metallic and metallic
      surfaces associated with poultry processing. Rubber 'fingers', plastic curtains,
      conveyor belt material and stainless steel test surfaces placed on the scald tank
      overflow and several chutes revealed extensive and often confluent bacterial
      biofilms. Extracellular polymeric substances, but few bacterial cells were
      visible on test pieces placed on evisceration equipment, spinchiller blades and
      the spinchiller outlet.

PMID- 8858864
TI  - Amounts of free amino acids during early sporulation in Saccharomyces cerevisiae.
AB  - The amount of free amino acids in cell-free extracts was examined during early
      sporulation of the yeast Saccharomyces cerevisiae. There was a slight decrease 2
      h after transfer to the sporulation medium followed by a slight increase.

PMID- 8858865
TI  - Mitogenic effects of mycotoxins on T4 lymphocytes.
AB  - Mycotoxins have compromising effects on varied biological systems, even when
      ingested at levels which do not evoke manifestations of clinical mycotoxicoses.
      No data have been previously found as to the therapeutic and mitogenic effects of
      mycotoxins. This was the objective of the present work. Human peripheral T4
      lymphocytes were obtained by venipuncture, propagated in RPMI 1640 medium and
      challenged with varied concentrations of aflatoxins, B1, B2, G1, and G2. The
      cells were stained with propidium iodide and fluorescent isothiocyanate (FITC)
      and examined microfluorometrically. All the mycotoxins were significantly
      mitogenic on the basis of dose response. No adverse effects were observed when
      doses of 10, 50 and 100 micrograms were administered on a modest clinical basis
      to volunteers.

PMID- 8858866
TI  - Large vesicle formation within cells induced by treatment with a mixed
      surfactant.
AB  - MDCK cells have been treated with a mixed surfactant at low concentrations to
      study the induced morphological changes. The most significant change at the light
      microscope level was the appearance of multiple large vesicles, which increased
      in size with time, up to approximately 40 microns in diameter. Vesicle formation
      was shown to be linked with the uptake of the fluid medium, as judged by the
      presence of FITC-dextran within the vesicles, but was not a result of pinocytosis
      because cytochalasin D treatment had no effect on their formation. Furthermore,
      nile red staining demonstrated that the vesicles did not represent fusion of pre
      existing lipid droplets. Transmission electron microscopy (TEM) analysis
      indicated that the vesicles lacked any obvious structure. It is hypothesised that
      the vesicles are large mixed structures synthesised as a result of interactions
      between cell membranes and detergent components after saturation with the
      surfactants. This effect is contrasted with the diffuse uptake of dyes and
      fluorescently labelled proteins following simple anionic or ionic detergent
      treatment. The effect of vesicle formation was reversible if the cells were
      placed in fresh medium lacking detergent. Other effects of mixed detergent
      included the loss of rounded compact colonies, an increase in mean cell diameter
      and the almost complete loss of surface microvilli as seen with scanning electron
      microscopy (SEM). In the TEM the cell ultrastructure was seen to have changed
      markedly following detergent treatment, with a loss of rough endoplasmic
      reticulum and an apparent clumping of the cytoplasmic constituents.

PMID- 8858867
TI  - Performance of a slow-scan CCD camera for macromolecular imaging in a 400 kV
      electron cryomicroscope.
AB  - The feasibility and limitations of a 1024 x 1024 slow-scan charge-coupled device
      (CCD) camera were evaluated for imaging in a 400kV electron cryomicroscope.
      Catalase crystals and amorphous carbon film were used as test specimens. Using
      catalase crystals, it was found that the finite (24 microns) pixel size of the
      slow-scan CCD camera governs the ultimate resolution in the acquired images. For
      instance, spot-scan images of ice-embedded catalase crystals showed resolutions
      of 8 A and 4 A at effective magnifications of 67,000 x and 132,000 x,
      respectively. Using an amorphous carbon film, the damping effect of the
      modulation transfer function (MTF) of the slow-scan CCD camera on the specimen's
      Fourier spectrum relative to that of the photographic film was evaluated. The MTF
      of the slow-scan CCD camera fell off more rapidly compared to that of the
      photographic film and reached the value of 0.2 at the Nyquist frequency. Despite
      this attenuation, the signal-to-noise ratio of the CCD data, as determined from
      reflections of negatively-stained catalase crystals, was found to decrease to
      approximately 50% of that of photographic film data. The phases computed from
      images of the same negatively-stained catalase crystals recorded consecutively on
      both the slow-scan CCD camera and photographic film were found to be comparable
      to each other within 12 degrees. Ways of minimizing the effect of the MTF of the
      slow-scan CCD camera on the acquired images are also presented.

PMID- 8858868
TI  - Biotechnology and biomimetic with crystalline bacterial cell surface layers (S
      layers).
AB  - Crystalline bacterial cell surface layers (S-layers) are the outermost cell
      envelope component of many eubacteria and archaeobacteria. S-layers are composed
      of a single protein or glycoprotein species and exhibit oblique, square or
      hexagonal lattice symmetry. Pores passing through these monomolecular arrays show
      identical size and morphology, and functional groups are aligned in well-defined
      positions and orientations. Due to these unique features, S-layers have broad
      application potential in biotechnology including functioning as biomimetic
      membranes. Presently, S-layers are used (i) for the production of isoporous
      ultrafiltration membranes with very well defined molecular sieving and adsorption
      properties, (ii) as matrices for the controlled immobilization of biologically
      active macromolecules (e.g., enzymes, antibodies, ligands) as required for
      biosensors, affinity membranes and affinity microparticles as well as for solid
      phase assays, (iii) as stabilizing structures for Langmuir-Blodgett films and
      liposomes and (iv) as carriers and adjuvants for weakly immunogenic antigens and
      haptens.

PMID- 8858869
TI  - Improved immuno double labelling for cell and structural biology.
AB  - Colloidal gold is the most widely used electron dense marker in biological
      electron microscopy. The development of procedures for making gold particles of
      very defined sizes has made double or even multiple labelling possible using gold
      of two or more different sizes. Lately a new type of electron dense marker has
      been developed consisting of ligand-stabilized metal atom clusters rather than
      colloidal particles. The differences between these two types of markers are
      highlighted and the advantages of using metal atom clusters for immuno labelling
      of certain biological specimens are discussed. Possible methods of distinguishing
      two such cluster labels in double labelling experiments are reviewed.

PMID- 8858870
TI  - A theoretical link between lenticular absorbance and fluorescence.
AB  - The age-related variation of the fluorescence of the human eye lens was
      calculated from published data for lenticular absorbance. Only the nucleus was
      assumed to be involved. Simplifying assumptions for nuclear geometry yielded
      axial point-by-point data of absorbance for the exciting and fluorescent beam
      intensities. The resulting fluorescence profiles and their variation with age
      were computed. The model was tested on two assumptions: yellowing of the lens
      involves a pigment (a) already present at, or (b) one accumulating from, birth.
      Agreement between theory and experiment follows from hypothesis (b), and supports
      an earlier suggestion that the lens may yellow owing to a lifelong exposure to
      light.

PMID- 8858871
TI  - A gradient from stable to cyclic populations of Clethrionomys rufocanus in
      Hokkaido, Japan.
AB  - A total of 31 years of abundance data from 90 populations of the grey-sided vole
      (Clethrionomys rufocanus) in northern Hokkaido (Japan) were analysed with respect
      to population dynamic characteristics. Both non-periodic and multi-annually
      periodic fluctuations occur among the studied populations. The length of the
      period varies from 2 to 5 years. The dynamics appear approximately linear on a
      logarithmic scale, and a log-linear stochastic difference model with one time-lag
      is found to recreate the periodograms of the time series. The deterministic (log
      linear) component of these models determines the periodicity while stochasticity
      sustains the cycles. The dynamics of the Hokkaidian vole populations are found to
      vary clinally from the western coast eastwards and towards the interior of the
      study area. This gradient corresponds superficially to the latitudinal gradient
      seen in microtine populations in Fennoscandia. However, under close scrutiny,
      these gradients differ greatly: the Hokkaidian gradient is caused by a cline in
      delayed density dependence. Statistical delayed density dependence is more
      negative towards the east and the interior.

PMID- 8858872
TI  - Axotomy-induced retinal ganglion cell death in development: its time-course and
      its diminution by antioxidants.
AB  - Developing neurons die when deprived of trophic support from their axonal target.
      Although this is generally attributed to the programmed expression of suicide
      proteins, recent data suggest that a less orderly mechanism involving oxidative
      stress may also be involved. We have studied retinal ganglion cell death in the
      chick embryo after a contralateral tectal lesion. The kinetics of cell death, as
      judged from counts of pyknotic cells, are described. In addition, we show that
      the pyknotic counts are reduced following intraocular injections of the protein
      synthesis inhibitor cycloheximide or the antioxidants N-t-butyl-alpha
      phenylnitrone and N-acetyl cysteine. Our results suggest that target deprivation
      induced ganglion cell death involves oxidative stress.

PMID- 8858873
TI  - Phenotypic segregation of Aedes aegypti for immune antibacterial activity and
      resistance to filariae.
AB  - We report the phenotypic selection of two lines of Aedes aegypti, from a filariae
      susceptible parental stock (Refm). This selection was based upon the level of
      inducible anti-gram negative Escherichia coli activity within the haemolymph
      following E. coli infection. These lines, denoted 'high' and 'low', demonstrated
      significant differences in anti-E. coli responses throughout. However no
      difference was observed in the anti-gram positive Micrococcus luteus response
      following E. coli challenge. F4, F6 and F9 mosquitoes were experimentally
      infected with Brugia pahangi microfilariae. Reductions of between 53 and 82% in
      the mean number of larvae completing development in the 'high' compared with the
      'low' responding line were observed. Corresponding reductions of between 30 and
      50% in the mosquito infection rates also occurred between these lines. These
      reductions were significant for trials on the F6 and F9 generations. We have
      therefore selected for Ae. aegypti possessing significant refractoriness to
      filaria infection. Importantly, this 'high' line has not been exposed to
      selection pressure using filariae development as a phenotypic selective marker.

PMID- 8858874
TI  - Impairment of the perception of second order motion but not first order motion in
      a patient with unilateral focal brain damage.
AB  - Unlike first order motion, which is based on spatiotemporal variations in
      luminance, second-order motion relies on spatiotemporal variation of attributes
      derived from luminance, such as contrast. Here we show that a patient with a
      small unilateral cortical lesion adjacent to human cortical area MT (V5) has an
      apparently permanent disorder in perceiving several forms of second-order but not
      first-order motion in his contralateral visual field. This result indicates that
      separate pathways for motion perception exist, either as divergent pathways from
      area MT or even from primary visual cortex, or as separate pathways from
      subcortical areas to extrastriate visual areas.

PMID- 8858875
TI  - Female chromosomes in cockerel ejaculates.
AB  - We describe a polymerase chain reaction which amplifies part of the Eco RI repeat
      unit of the fowl W chromosome. The resulting 447 bp fragment enables DNA from
      female birds to be identified. The composition of this DNA is confirmed by a
      nested polymerase chain reaction which specifically amplifies a known internal
      263 bp region in this fragment. Using this technique it is possible to follow the
      fate of female cells in male germline chimaeras. The polymerase chain reaction
      fragment can be traced in cells of the embryonic and hatchling gonad and in adult
      sperm implying that cells containing the W chromosome are capable of being
      processed through the avian testis.

PMID- 8858876
TI  - Sex identification in birds using two CHD genes.
AB  - In theory, birds should control the sex ratio of the offspring they produce. In
      practice, we have very limited evidence to support this idea because of our
      difficulty in sexing nestling birds. In addition, extinction is facing an
      increasing number of birds. Our ability to help includes captive breeding which,
      again, is difficult if male and female adults cannot be recognized. Here we
      describe the discovery of a W-linked gene in the Great tit (Parus major). It is
      named CHD-W (chromodomain-helicase-DNA-binding protein W-linked), it is highly
      conserved and it is W-chromosome linked in a range of bird species. These birds
      also possess a second, non-W-linked CHD gene (CHD-NW). A single, simple
      polymerase chain reaction technique based on both genes can be used to identify
      the sex in a wide variety of birds.

PMID- 8858877
TI  - Ultrastructural evidence of adrenergic, as well as cholinergic, nerve
      varicosities in relation to the lamina propria of the human seminiferous tubules
      during childhood.
AB  - The ultrastructure of autonomic nerve fibers and terminal varicosities is
      described in relation to the lamina propria of the human seminiferous tubules
      during childhood (age 3 to 10 years). Autonomic nerve varicosities are classified
      as: Type I with numerous small (30-60 nm) agranular vesicles and variable numbers
      of large (100 nm) granular vesicles, and Type II with numerous small (30-60 nm)
      granular vesicles and sporadic large granular vesicles. These two varicosity
      types are consistent in morphology with cholinergic and adrenergic nerve
      terminals, respectively. Nerve varicosities are found, associated with Schwann
      cells, in proximity to the cells of the lamina propria. Although not found in
      direct "synaptic' contact, these autonomic endings are often within a few hundred
      nanometers of the cellularity of the lamina propria. The Schwannian sheath is
      interrupted over the varicosities at these sites and occasionally the terminal
      varicosities are totally lacking a Schwann sheath. These findings are consistent
      with the structural relationship of autonomic nerve "terminals' and effector in
      other endocrine and non-endocrine systems. This is the first evidence of
      adrenergic nerve varicosities in proximity to the lamina propria in humans (at
      any age). Evidence is also presented which suggests a locational difference in
      the distribution of cholinergic (Type I) and adrenergic (Type II) nerve
      varicosities in this region, with only cholinergic endings observed directly
      adjacent to the basal lamina of the seminiferous tubules.

PMID- 8858878
TI  - Structural changes in the intramuscular connective tissue during development of
      bovine semitendinosus muscle.
AB  - Structural changes in the intramuscular connective tissue during development of
      bovine semitendinosus muscle were investigated using the cell-maceration method
      for scanning electron microscopy, by which cellular elements were eliminated and
      collagen fibrils and fibres were exposed. The endomysium was discontinuous and
      showed various shapes and sizes in the muscle of 7-month fetuses. The perimysium
      consisted of collagen fibres in loose contact with each other. In the muscle of
      neonatal calves, the endomysium consisted of cylindrical sheaths and displayed a
      honeycomb structure, and the perimysium was composed of several layers of
      collagen fibres. Collagen fibrils in the endomysium bound ever more closely with
      each other, and collagen fibres in the perimysium increased in thickness, and the
      wavy pattern of collagen fibres became more regular with growth of cattle. We
      have examined the mechanical strength of the intramuscular connective tissue by
      our new method, 'intramuscular connective tissue (IMCT) model'. The IMCT model is
      composed of collagen fibrils and fibres which maintains the organization in the
      endomysium and perimysium in situ. The shear-force value of the model increased
      rapidly from the 7th fetal month to the neonatal stage, and increased linearly
      with postnatal ageing thereafter. Changes in the arrangement of collagen fibrils
      and fibres seem to closely related to an increase in the mechanical strength of
      the intramuscular connective tissue during development of bovine skeletal muscle.

PMID- 8858879
TI  - Cytoplasmic desmosome formation by H-7 and EGF treatment in cultured fetal rat
      keratinocytes.
AB  - Cytoplasmic desmosomes (CD) are classically found in dyskeratotic cells of many
      epithelial tumors. Their significance and mechanism of formation remain largely
      speculative. Recently, we have reported the induction of these structures in rat
      keratinocytes following a brief treatment with acrylamide, and proposed that
      protein kinase inhibition may be implicated in their formation. In the present
      study, we show that protein kinase inhibitor H-7 in the presence of EGF is able
      to induce CD in rat keratinocytes within half an hour. In serum free medium
      containing 20 ng/ml of EGF, desmosomal structures at different stages of assembly
      were obtained using H-7 at concentrations ranging between 20 and 80 microM. No
      such structures were found at lower concentrations. The plaque diameters were
      significantly small in comparison with plasma membrane plaques. EGF induced
      plakoglobin positive membrane invaginations and in the presence of H-7,
      desmosomal plaques assembled on these membranes as either half desmosomes or as
      symmetric ones. The present results implicate protein kinase inhibition in CD
      formation and suggest that EGF provides tubular membrane structures in the
      cytoplasm on which desmosomes may assemble.

PMID- 8858880
TI  - Evidence for multiple satellite cell populations and a non-myogenic cell type
      that is regulated differently in regenerating and growing skeletal muscle.
AB  - We have performed studies to determine if different populations of satellite
      cells provide nuclei to growing and regenerating skeletal muscle fibers.
      Satellite cells were isolated from regenerating or growing anterior tibialis
      muscles, and their phenotypic properties were compared in vitro. Isolates from
      regenerating muscle contained 31% satellite cells, and those from control muscle
      contained 66% satellite cells, as determined by their expression of desmin. Among
      the desmin-positive satellite cells present from each preparation, two distinct
      populations of satellite cells were evident. Approximately 28% of satellite cell
      colonies were composed of only large cells, contained less than 50 cells/colony,
      and were designated as type 1 colonies. The remainder of satellite cell colonies
      isolated from either regenerating or control muscles were primarily composed of
      small cells, contained from 60 to 150 cells/colony, and were designated as type 2
      colonies. Despite dramatic differences in the ratio of myogenic to non-myogenic
      cell types, satellite cells from regenerating and control muscles formed myotubes
      and expressed myosin heavy chain at similar levels. Treatment of regenerating
      cultures with dexamethasone resulted in a 16% increase in the number of desmin
      positive colonies and dramatically decreased the proliferation of non-myogenic
      cells. These results suggest that at least two distinct populations of satellite
      cells can be isolated from regenerating and control skeletal muscles, and that
      non-myogenic cells are differentially regulated in regenerating versus non
      regenerating environments.

PMID- 8858881
TI  - Tissue and cell distribution of copper, zinc and cadmium in the mussel, Mytilus
      galloprovincialis, determined by autometallography.
AB  - The localization of metals in selected tissues of metal-exposed mussels was
      investigated by means of autometallography. Mussels collected from a Zn-polluted
      site were (a) depurated or, alternatively, (b) exposed to either Cu, Zn or Cd for
      41 d. Mussels collected from a clean site were used as experimental reference.
      Autometallographically demonstrated black silver deposits (BSD), indicating the
      presence of metals, were observed in gills, (a) in frontal cells and haemocytes
      of Cu-exposed mussels, (b) in secretory postlateral and abfrontal cells and in
      endothelial cells of Zn-exposed mussels, and (c) in frontal, postlateral and
      endothelial cells but mainly in abfrontal cells and haemocytes of Cd-exposed
      mussels. Autometallography also revealed the presence of BSD in connective tissue
      brown cells underlying the mantle. Additionally, adipogranular cells of the
      connective tissue surrounding the gonad follicles were positively stained but no
      BSD was found in gonad tissue. Scarce BSD were found in the cytoplasmic granules
      of the stomach wall of control mussels whilst depurating and metal-exposed
      mussels exhibited BSD lining the apex of the stomach epithelial cells. Contrary
      to the results previously obtained with marine gastropod molluscs, BSD were not
      found in the basal lamina of digestive tubules, stomach, and ducts of mussels.
      Highly conspicuous BSD were observed in digestive cell lysosomes of depurating
      and metal-exposed mussels. Basophilic cells were always devoid of BSD. Finally,
      BSD were also found in nephrocyte lysosomes and mineralized concretions.

PMID- 8858882
TI  - A comparative and ultrastructural study of synaptic contacts established by
      primary sensory fibers in the spinal trigeminal nucleus of the rat.
AB  - A quantitative evaluation of the types of afferent synaptic contacts in the pars
      oralis, using transganglionic degeneration and a comparison of previous data
      obtained from the pars interpolaris (Lapa & Bauer, 1992), of the rat was
      performed. Following left inferior alveolar nerve transection or partial
      pulpectomy of the first and second left lower molar teeth well-defined
      degenerating terminals appeared bilaterally. In both experiments, the majority of
      these afferent synapses formed single asymmetric contacts with intermediate and
      distal dendritic segments in the pars oralis. Fewer contacts were observed with
      dendritic spines, proximal dendritic segments, perikarya, and other terminals.
      Double and multiple synaptic contacts, preferentially with small dendritic
      profiles, were also found. Pars oralis showed higher density of degenerating
      terminals and higher proportion of the contralateral contacts than pars
      interpolaris suggesting that it is a prime input area and that it may play a role
      in the bilateral management of sensory information. Pars oralis showed a higher
      density of contacts with intermediate and distal dendritic segment and a lower
      density of double contacts in comparison to the pars interpolaris. Partial
      pulpectomy revealed a distribution in synaptic types similar to that following
      IAN transection suggesting that sensory fibers conveying pain-related stimuli are
      not distinguished from fibers of other sensory modalities as to preference of
      synaptic contacts. The overall pattern demonstrates a structural organization of
      the sensory inputs to the spinal trigeminal nucleus regarding the bilateral
      handling of sensory information.

PMID- 8858883
TI  - The adenohypophysis of Mediterranean yellowtail, Seriola dumerilii (Risso, 1810):
      an immunocytochemical study.
AB  - The adenohypophysis (ADH) of the Mediterranean yellowtail was studied using the
      peroxidase-antiperoxidase technique. Human corticotropin (ACTH) (1-24)
      immunoreactive (ir) cells were found bordering the neurohypophysis (NH) and
      salmon prolactin (PRL)-ir cells were arranged in thick cords, both in the rostral
      pars distalis (RPD). Gonadotropin (GTH)-, thyrotropin (TSH)- and growth hormone
      (GH)-ir cells were observed in the proximal pars distalis (PPD). Anti-chum salmon
      GTH I and anti-chum salmon GTH II immunostained the same cells in the outermost
      part of the ADH at the level of the PPD and the PI. In addition to these cells,
      some cells grouped in the inner areas of the posterior PPD were revealed by
      catfish alpha, beta-GTH antiserum. Human beta-TSH-ir cells formed small groups
      and discontinuous strands in the PPD often in contact with the NH. Tilapia GH-ir
      cells formed cords mainly surrounding the NH in the central PPD, while cod
      somatolactin- and alpha MSH-ir cells mainly surrounded the NH branches in the PI.

PMID- 8858884
TI  - Induction of ACTH- and TNF-alpha-like molecules in the hemocytes of Calliphora
      vomitoria (Insecta, Diptera).
AB  - Three basic cell types are described in the hemolymph of newly enclosed adult
      Calliphora vomitoria: prohemocytes, plasmatocytes, and granular cells. In
      addition, anucleate cellular fragments with some inclusions are observed. Cell
      division is found only in the prohemocytes. Plasmatocytes and granular cells are
      capable of in vitro bacterial phagocytosis and take part in capsule formation.
      Adrenocorticotropin hormone (ACTH)-like molecules are found in both cell types.
      The staining of the plasmatocytes is related to the functional activation of the
      cells. Indeed, positive staining is only observed during capsule formation,
      suggesting an induction of ACTH expression. The behaviour of tumor necrosis
      factor (TNF)-alpha-like molecules is similar. In conclusion, these data provide
      further support for the close, evolutionary relationship between the immune and
      the neuroendocrine systems.

PMID- 8858885
TI  - Neurons and microvessels of the nodose (vagal sensory) ganglion in young adult
      and aged rats: morphometric and enzyme histochemical studies.
AB  - The neuron cell bodies and microvessels in sections of the nodose (vagal sensory)
      ganglion (NG) of Wistar rats of 4- and 24-months of age have been examined
      morphometrically and by quantitative enzyme histochemistry. The range of neuronal
      somata areas was similar at the two ages and distributed unimodally, ranging
      approximately from 200-1500 microns 2 with the largest somata occurring in the
      older age group. The range of microvessel diameters was also comparable but the
      largest microvessels were seen in the older animals. The histological arrangement
      of the ganglion permitted analyses to be made of 'neuronal' and 'axonal' areas
      independently. The number of microvessels per unit area was less in regions of
      the ganglion occupied by axons at both ages. Random transects indicated that the
      percentage area occupied by neuron somata decreases and that of axons increases
      with age. Overall, however, the results suggest that the histological
      organization, the size of vagal sensory neurons, the ganglionic microvessels, and
      the relationship between them, does not change greatly in Wistar rats of up to 2
      years of age. Ultrastructural features of the aged sensory neurons included the
      presence of secondary lysosomes, disrupted rough endoplasmic reticulum, swollen
      Golgi cisternae, and the presence of much filamentous material in the perikaryon
      similar to that seen in chromatolytic neurons. However, analysis of electron
      micrographs did not reveal significant changes in the numbers of mitochondria or
      Golgi bodies. There was an overall increased thickness in the microvascular wall
      in the older animals with the endothelium and pericyte covering being
      significantly increased, but the thickness of the basal lamina was unchanged. The
      activities of neuronal NADH tetrazolium reductase, succinate dehydrogenase and
      cytochrome oxidase were all increased with age. The results suggest that vagal
      sensory neurons are not greatly affected by age in the rat.

PMID- 8858886
TI  - Iron and infection.

PMID- 8858887
TI  - Burkholderia (Pseudomonas) cepacia and cystic fibrosis: the epidemiology in
      Belgium.
AB  - Burkholderia cepacia has become an increasingly recognized pathogen among cystic
      fibrosis (CF) patients and its potential role in declining pulmonary function or
      unexpected fatal outcome has caused widespread concern. Direct person-to-person
      transmission has been documented and a segregation policy of CF patients
      colonized with B.cepacia from non-colonized CF patients is widely adopted. Since
      this policy has a dramatic impact on social behaviour of CF patients it is
      imperative that clinical laboratories accurately isolate and identify B.cepacia
      in the respiratory secretions. In order to comprehend the epidemiology of
      B.cepacia in the Belgian CF population a multicentre study was conducted during a
      period of 1 year (March'93-February'94). B.cepacia was isolated in only 12 of 465
      CF patients (2.6%). Routine biochemical tests identified these strains as
      authentic B.cepacia. However, the combined data from protein and DNA-DNA
      hybridization analyses revealed that the Belgian CF "B.cepacia" isolates showed
      patterns different from reference B.cepacia isolates and belong to 3 different,
      newly identified Burkholderia genomovars, but not to B.cepacia. Comparative
      analysis of the selective media used for recovery of these "B.cepacia" strains
      from respiratory secretions indicated that the commercial medium (Mast)
      containing polymyxin B and ticarcillin as the selective agents was the best and
      most user-friendly. Molecular typing of these Burkholderia isolates by
      arbitrarily-primed PCR (AP-PCR) and pulsed-field gel electrophoresis (PFGE)
      showed that spread of a single strain within a same centre occurred but the mode
      of transmission remains unknown; inter-centre spread of strains was not observed.
      Interestingly, neither colonization with a distinct or an epidemic strain
      (belonging to either of the three newly identified Burkholderia genomovars) nor
      colonization for a prolonged period of time, led to a rapid deterioration of lung
      function in these CF patients. It appears essential to determine the prevalence
      of these "new" Burkholderia genomovars in larger populations of CF patients and
      to evaluate their virulence and other features as this may have important
      clinical and practical implications.

PMID- 8858888
TI  - Epidemiology of microalbuminuria in type 1 diabetic patients (IDDM) in the
      Antwerp University Hospital.
AB  - Diabetic nephropathy is the most important cause of increased morbidity and
      premature mortality in patients with insulin dependent diabetes mellitus. Several
      longitudinal studies done in different countries have shown that microalbuminuria
      strongly predicts the development of diabetic nephropathy in insulin dependent
      diabetes mellitus. Very few data are available about the situation in Belgium. In
      a retrospective study we analysed the data of 271 insulin dependent diabetic
      patients attending the University Hospital of Antwerp during the year 1994.
      Normoalbuminuria was defined as a urinary albumin excretion rate of < or = 20
      micrograms/min, microalbuminuria as 20-200 micrograms/min and macroalbuminuria as
      > 200 micrograms/min. In our population we find an overall prevalence of
      microalbuminuria of 14%. Patients with microalbuminuria are characterised by an
      earlier onset and a longer duration of diabetes when compared with patients with
      normoalbuminuria. Further we find that they have a worse glycemic control, a
      higher frequency of raised arterial blood pressure and a higher percentage of
      proliferative retinopathy. These data are comparable with those from other
      studies done in different countries. They show that patients with
      microalbuminuria should be regarded as a high risk group and therefore urinary
      albumin excretion rate should be monitored routinely. Also they stress the
      importance to strive to a good metabolic control and to an aggressive treatment
      of arterial hypertension.

PMID- 8858889
TI  - In vitro susceptibilities of 180 clinical isolates of Haemophilus influenzae to
      ampicillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime,
      clarithromycin, and azithromycin.
AB  - One hundred eighty consecutive, unduplicate isolates of Haemophilus influenzae
      from clinical specimens collected from November 1994 through February 1995 in
      nine general hospitals throughout Belgium were examined for beta-lactamase
      production using a nitrocefin-based test, and for their in vitro susceptibilities
      to ampicillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime,
      clarithromycin and azithromycin by means of the NCCLS agar dilution test. The
      isolates were all from respiratory tract specimens. The prevalence of capsular
      type b was 1.1%, and the overall rate of beta-lactamase production 16.7%. Rates
      of beta-lactamase production were higher in isolates from children (22.0%) than
      in those from adults (15.3%), and in isolates from upper respiratory tract
      specimens (22.0%) than in those from the lower respiratory tract (15.1%). Beta
      lactamase-negative ampicillin resistance amounted to 1.1%. Cefotaxime had the
      highest activity on a weight basis [MIC (minimal inhibitory concentration) for
      50% of the isolates tested (MIC50) < or = 0.06 microgram/ml], followed by
      ampicillin (MIC50 of 0.25 microgram/ml), amoxycillin/clavulanate and cefuroxime
      (MIC50 of 0.5 microgram/ml), azithromycin (MIC50 of 2 micrograms/ml), cefaclor
      (MIC50 of 4 micrograms/ml), and clarithromycin (MIC50 of 8 micrograms/ml).
      Cefotaxime was also the most active drug in terms of susceptibility rates of the
      isolates (100.0%), followed by amoxycillin/clavulanate and azithromycin (98.9%),
      cefuroxime (97.2%), cefaclor (89.4%), clarithromycin (82.8%), and ampicillin
      (82.2%). In conclusion, amoxycillin/clavulanate and cefuroxime retain an
      excellent activity against H. influenzae, while cefaclor lost some of its
      activity. The rate of susceptibility to azithromycin was markedly higher than
      that to clarithromycin; however, its ability to accumulate intracellularly while
      concentrations in serum and interstitial fluid remain low, should be considered,
      as it may represent a major drawback to its use in H. influenzae infections.

PMID- 8858890
TI  - Thoracoscopic sympathicolysis for essential hyperhidrosis: immediate and one year
      follow-up results in 35 patients and review of the literature.
AB  - Various treatments for essential hyperhidrosis are available. The aim of this
      study is to present our experience with a simplified thoracoscopic
      sympathicolysis technique in this disorder, and to confront our results with data
      in the literature, 35 consecutive patients (11 male, 24 female, age 12-44 years)
      with essential hyperhidrosis, refractory to "conventional" medical treatment
      presenting between August 1993 and May 1994 were studied. Bilateral D2-D3
      sympathicolysis was performed using a simplified one-time bilateral thoracoscopic
      procedure under general anaesthesia. Clinical scores, complications and side
      effects were recorded one week, one month and one year after the intervention.
      Severe hyperhidrosis was present in the hands in 100%, axillae in 66% and soles
      of the feet in 86% of patients. In one patient, only a unilateral intervention
      was possible due to pleural adhesions. In the other 34 patients, palmar
      hyperhidrosis was completely and permanently relieved in 100% of cases. Axillar
      hyperhidrosis was significantly improved after one year in 91% of patients, 52%
      of which showed a complete disappearance of hyperhidrosis. Side effects and
      complications were minimal. There were no permanent pleural, neurological
      (Horner) or other sequellae. Patient satisfaction was invariably very high. These
      findings compare favourably with historical data in the literature.

PMID- 8858891
TI  - Cytochrome P450: genetic polymorphism and drug interactions.
AB  - In this review, after a short discussion of our knowledge about cytochrome P450
      isoenzymes, two important sources of variability in the metabolism of drugs by
      cytochrome P450 are described, i.e. genetic factors and drug-drug interactions.
      Many hepatic cytochrome P450 enzymes play an important role in the oxidative
      biotransformation of numerous drugs and other foreign compounds, and of many
      endogenous substrates. In humans more than 20 different isoenzymes of cytochrome
      P450 responsible for the hepatic metabolism of drugs, have been identified. They
      are classified into families and subfamilies on the basis of the degree of amino
      acid similarity. Cytochrome P450 isoenzymes are regulated by both genetic and
      environmental factors. Of particular interest is genetic polymorphism in drug
      oxidation. Two genetic polymorphisms in drug oxidation are well known, the
      sparteine/debrisoquine (CYP2D6) polymorphism and the mephenytoin oxidation
      (CYP2C19) polymorphism. As a result of these polymorphisms, two phenotypes exist
      in the population, poor and extensive metabolizers. Poor metabolizers may be
      prone to adverse reactions towards drugs with a narrow therapeutic range. In
      extensive metabolizers clinically significant drug interactions between drugs
      metabolized by the same isoenzyme can occur.

PMID- 8858892
TI  - Endobronchial inflammatory pseudotumour in a patient with B-cell chronic
      lymphocytic leukemia and malignant pleural mesothelioma.
AB  - We report the case of a patient with B-cell chronic lymphocytic leukemia,
      presenting with cough and pain in the right hemithorax. The diagnosis of an
      inflammatory pseudotumour in the right lower lobe bronchus was made. Clinical
      presentation, pathology and treatment of this uncommon tumour-like lesion are
      briefly discussed.

PMID- 8858893
TI  - Bacteraemia with Leptotrichia buccalis: report of a case and review of the
      literature.
AB  - We report here on a new case of L. buccalis bacteraemia. To our knowledge 16
      other cases of L. buccalis bacteraemia have been reported in the literature, most
      of them in neutropenic patients. However L buccalis endocarditis does
      occasionally occur in non-neutropenic patients. The identification of L. buccalis
      is based on well known phenotypic features and confirmed by the detection of a
      large peak of lactic acid by gas chromatography for non volatile organic acids.
      L. buccalis is sensitive to a wide range of antibiotics including beta-lactam
      antibiotics, but it is resistant to aminoglycosides and macrolides.

PMID- 8858894
TI  - Dermatomyositis and bronchial squamous cell carcinoma: evidence for a true
      relationship.
AB  - The authors report a case of dermatomyositis (D.M) in a 57-year-old man,
      associated with a squamous cell bronchial carcinoma. The complete resolution of
      the dermatomyositis after radical resection of the bronchial tumor strongly
      suggested a paraneoplastic phenomenon.

PMID- 8858895
TI  - A case of total peripheral aneosinophilia associated with complete deficiency of
      myeloperoxidase.
AB  - Complete and permanent absence of peripheral eosinophilic granulocytes was
      observed in a patient also presenting with total myeloperoxidase deficiency. The
      anomaly was suspected because of complete absence of the eosinophilic cluster in
      the display of a H*3 Technicon hematological automate and was confirmed by
      traditional staining of more than 100,000 leukocytes. A severe infectious problem
      during adolescence could be related to MPO deficiency in this patient. No
      specific disorder attributable to aneosinophilia was however observed
      subsequently.

PMID- 8858896
TI  - Ultrasonography of the knee.
AB  - Despite the increasing use of MRI in knee disorders, ultrasonography remains the
      first choice examination technique in para-articular disease. The technique is
      fast, cheap, easily accessible and usable in the acutely injured patient. The
      choice of equipment, positioning of the patient and some characteristics of
      normal anatomy are described. The routine applications of ultrasonography include
      different types of tendon disease, trauma of the collateral ligaments, bursal
      pathology, joint effusions and synovitis, evaluation of the popliteal fossa and
      para-articular swellings. Other possible applications, somewhat more depending on
      the examiner's experience, are meniscal disease, trauma to the cruciate ligaments
      and evaluation of the articular cartilage and synovial plicae.

PMID- 8858897
TI  - Primary biliary cirrhosis and bone changes.
AB  - Two cases of primary biliary cirrhosis with bone lesions are reported. In one
      case radiographic findings in the hands and right shoulder are found to be
      characteristic of primary biliary cirrhosis rather than other concomitant
      diseases present in the patient which are also susceptible to produce bone
      lesions. The second case is an example of less specific bone changes which may be
      attributed to primary biliary cirrhosis or other rheumatoid disease.

PMID- 8858898
TI  - Endometrioid cystadenocarcinoma of the ovary.
AB  - The authors present the US- and CT-findings in a patient with endometroid
      cystadenocarcinoma of the right ovary. The importance of detecting a small solid
      component in an otherwise typical "endometrioma" is stressed. The contribution of
      MR is discussed.

PMID- 8858899
TI  - Strecker stent placement in the superior mesenteric artery for recurrent ischemic
      colitis.
AB  - We report on a case of recurrent superior mesenteric artery (SMA) stenosis with
      symptomatic mesenteric angina after SMA angioplasty. Stent placement of
      postostial atherosclerotic disease was proposed, with successful result. Moderate
      aortic protrusion was noted. Feasibility of PTA and stenting of mesenteric
      stenoses become increasingly obvious, but long term follow-up studies still have
      to provide sufficient results on clinical outcome and possible complications.

PMID- 8858900
TI  - Aortic coarctation associated with an aberrant right subclavian artery.
AB  - We report a case of aortic coarctation associated with an aberrant right
      subclavian artery in a young male who was investigated for hypertension.
      Angiography, CT examination with multiplanar reconstruction and MRI were useful
      in delineating the extension of the coarctation and the exact anatomy of the
      aberrant right subclavian artery.

PMID- 8858901
TI  - Diagnosis and endovascular treatment of midbasilar dissecting aneurysm.
AB  - The authors present the case of a patient with a midbasilar dissecting aneurysm
      successfully treated by staged bilateral endovascular occlusion of the vertebral
      artery. The clinical and the radiological features are presented with references
      to the literature, and the choice of endovascular rather than neurosurgical
      treatment is discussed in light to our previously reported experience about the
      treatment of unclippable vertebrobasilar aneurysms.

PMID- 8858903
TI  - Crocidolite and not chrysotile was mainly used by the Italian railroad system.

PMID- 8858904
TI  - Unreliability of echocardiographic and Doppler indexes in the diagnosis of heart
      transplant acute rejection.
AB  - OBJECTIVE: To investigate the value of Doppler echocardiography to diagnose heart
      transplant acute rejection in both patients submitted to the standard surgical
      technique (Group A), and to a new technique that preserves the size of the left
      atrium and leaves the right atrium intact (Group B). METHODS: 122 Doppler
      echocardiographic studies and endomyocardial biopsies were performed on 27 group
      A and 11 group B patients. Systolic measurements included left ventricular
      shortening fraction, left ventricular endsystolic stress and tricuspid ring
      systolic displacement. Diastolic indexes investigated were left and right
      ventricle filling and superior vena caval flow parameters. RESULTS: As expected,
      right atrium was smaller in group B(p < 0.01). In group A, peak early to late
      mitral flow velocity increased, as did the rejection grade; whereas in group B it
      decreased. Pericardial effusion was seen more frequently in group B rejectors (>
      or = 3) than non-rejectors (63% vs 27%, p < 0.01). Right heart pressures (right
      ventricular end-diastolic and right atrial mean) were slightly higher for group A
      and B rejector patients (p < 0.05 when comparing right ventricular end-diastolic
      pressure in rejector to non-rejector group B patients). Left ventricular
      isovolumic relaxation time was reduced during subsequent rejection episodes in
      the same patient, but sensitivity of 15% left ventricular isovolumetric
      relaxation time reduction for rejection > or = 3 diagnosis was only 22% with a
      specificity of 73%. No significant intrapatient changes were found in other
      Doppler-derived systolic or diastolic indexes. CONCLUSION: Doppler
      echocardiography does not diagnose heart transplant acute rejection with enough
      reliability to avoid endomyocardial biopsies.

PMID- 8858905
TI  - Diagnosing cardiac rejection by echocardiography.

PMID- 8858906
TI  - Chitinase activity of Xenorhabdus and Photorhabdus species, bacterial associates
      of entomopathogenic nematodes.
AB  - Xenorhabdus nematophilus (three strains), Xenorhabdus bovienii (one strain), and
      Photorhabdus luminescens (one strain) showed both exo- and endochitinase activity
      using p-nitrophenyl-N-acetyl-beta-D-glucosaminide and p-nitrophenyl-beta-D
      N,N',N'-triacetylchitotriose, respectively, as substrates. One to three bands
      were detected on PAGE gel with glycol chitin after electrophoresis. Variation in
      exo- and endochitinase activity among different species and strains was detected
      with the strongest activity in X. nematophilus and the weakest in P. luminescens.
      The primary form of X. bovienii had significantly greater chitinase activity than
      the secondary form, whereas their growth rate and total protein released into
      culture medium were similar. The partially purified chitinase of X. bovienii
      showed significant antimycotic activity against conidial germination and germ
      tube elongation of Botrytis cinerea.

PMID- 8858907
TI  - The production of cricket paralysis virus in suspension cultures of insect cell
      lines.
AB  - The yields of cricket paralysis virus from two insect cell lines propagated in
      suspension culture were examined. Although Trichoplusia ni (TN368) cells produced
      more virus per cell than Drosophila line 2 (DL2) cells, the smaller DL2 cells
      reached a higher cell density. Thus the difference in production between TN368
      and DL2 cultures was minimal. In mixed infections of Flock House virus and
      cricket paralysis virus (CrPV), CrPV was the predominant virus produced despite
      being present at a much lower multiplicity of infection.

PMID- 8858908
TI  - Cytoskeletal F-actin polymerization from cytosolic G-actin occurs in the
      phagocytosing immunocytes of arthropods (Limulus polyphemus and Gromphadorhina
      portentosa): does [cAMP]i play any role?
AB  - Phagocytosis is a major defense reaction in arthropods and is accomplished by two
      blood cells (hemocytes), the granulocyte (GRs) and plasmatocytes (PLs),
      collectively called immunocytes. Immunocytes (principally the GRs) from two
      arthropods, Limulus polyphemus (horseshoe crab) and Gromphadorhina portentosa
      (Madagascar hissing cockroach) effectively phagocytose fluorescein isothiocyanate
      (FITC)-conjugated fluoresbrite microspheres (FITC-FM) and chicken (Gallus
      domesticus) erythrocytes within 1 hr of incubation. Although actin polymerization
      and changes in intracellular cAMP ([cAMP]i) levels occur during the early stages
      of phagocytosis in vertebrates, these two phenomena have not been studied in
      arthropod immunocytes. Using the DNase I inhibition assay, we found a decrease in
      cytosolic G-actin and an increase in the cytoskeletal F-actin in the
      phagocytosing immunocytes; the total actin in both resting and phagocytosing
      immunocytes remained constant. These results showed an 86% increase in F-actin in
      G. portentosa immunocytes and a 29% increase in those of L. polyphemus after 1 hr
      of initial incubation with FITC-FM. As in some vertebrates, the role of [cAMP]i
      in the early stages of phagocytosis in these two animals- and perhaps in
      arthropods in general-is variable; although we detected some negligible amounts
      of [cAMP]i (0.10-0.80 pmol/cell at different time intervals) in L. polyphemus
      immunocytes, it was inconclusive whether those in G. portentosa also contained
      [cAMP]i. Even in L. polyphemus, the difference in the amounts of [cAMP]i in
      resting and phagocytosing cells was insignificant (P > 0.05). It was also
      inconclusive whether [Ca2+]i and/or [Mg2+]i play any roles in the early stages of
      phagocytosis in the two arthropods in this study. These results suggest that the
      two phenomena (F-actin polymerization and levels of [cAMP]i in arthropods) are
      basically similar to those in vertebrate neutrophils and macrophages, which
      suggests that certain immunological mechanisms are conserved in nature.

PMID- 8858909
TI  - Enhancin, the granulosis virus protein that facilitates nucleopolyhedrovirus
      (NPV) infections, is a metalloprotease.
AB  - Enhancin is a Trichoplusia ni granulovirus protein that facilitates
      nucleopolyhedrovirus (NPV) infections in lepidopterans. Gel filtration and ion
      exchange chromatography and immobilized alpha-macroglobulin were used to purify
      this protein and the removal of the contaminating proteases did not diminish the
      in vivo or in vitro activity of enhancin. Metal chelators were the only protease
      inhibitors capable of preventing digestion of the peritrophic membrane (PM)
      proteins by enhancin, indicating that enhancin is a metalloprotease. In addition,
      the canonical zinc binding site, HEXXH, found in most metalloproteases, was
      identified in the sequences of enhancins from three different granuloviruses. The
      identity of enhancin as a metalloprotease that facilitates NPV infections in
      lepidopterous larvae was confirmed by the expression of enhancin in a recombinant
      Autographa californica MNPV-baculovirus system and the purification of a
      recombinant enhancin that was active in neonate bioassays and that digested
      specific PM proteins. The recombinant enhancin was also inhibited by metal
      chelators and both the native and recombinant enhancin could be reactivated by
      divalent ions, further confirming that enhancin is a metalloprotease.

PMID- 8858910
TI  - Effect of cucurbitacin D on in vitro growth of Xenorhabdus and Photorhabdus spp.,
      symbiotic bacteria of entomopathogenic nematodes.
AB  - In vitro assays were conducted to determine the effect of cucurbitacin D, an
      oxygenated tetracyclic triterpenoid found in cucurbits, on the growth of
      Xenorhabdus isolated from Steinernema carpocapsae (All, Mexican, Agriotos
      strains), Steinernema riobravis, Steinernema glaseri (NC strain, strain 27), and
      Photorhabdus from Heterorhabditis bacteriophora (NC, Lewiston strains), and
      Heterorhabditis sp. (FL2122 strain). Cucurbitacin D inhibited the growth of four
      isolates, had no effect on the growth of four isolates, and stimulated the growth
      of one isolate. Results are discussed in relation to progeny production of
      entomopathogenic nematodes from insects that have eaten plant material containing
      cucurbitacin D. This is the first report of an effect of a plant secondary
      compound on the bacterial symbionts of entomopathogenic nematodes.

PMID- 8858911
TI  - Larvicidal activity of the symbiotic bacterium Xenorhabdus japonicus from the
      entomopathogenic nematode Steinernema kushidai against Anomala cuprea
      (Coleoptera:Scarabaeidae).
AB  - The entomopathogenicity of the symbiotic bacterium Xenorhabdus japonicus and the
      nematode Steinernema kushidai was determined. Phase I and II X. japonicus were
      cultured on an artificial medium and inoculated into the test insect or
      established into axenic S. kushidai populations. When 100, 1000, or 10,000
      bacterial cells of phase I or II were directly injected into the hemocoels of 3rd
      instar cupreous chafer, Anomala cuprea, both phases in the late log period killed
      100% of the larvae by the 2nd day postinoculation. However, both phases in the
      stationary period were less pathogenic with cupreous chafer mortality < 20 and
      80% at 100 and 1000 bacterial cells/ larva, respectively. In vitro studies showed
      that axenic S. kushidai provided with phase I or II symbionts grew well and
      produced equal numbers of progeny on a dog food medium, but nematodes with no
      symbionts did not grow at all. Pig liver extracts added as a dietary supplement
      to the dog food medium completely restored growth and progeny production of the
      nematode with no bacterial cells. Studies were conducted with infective juveniles
      (IJs) harboring phase I or II or no symbionts that were applied against 3rd
      instar cupreous chafer larvae in compost or injected directly into their
      hemocoels. In the compost study, IJs harboring phase I killed 100% within 10
      days. IJs with phase II or no symbionts caused low mortality of the cupreous
      chafer larvae at 10 days (< 20%). In the intrahemocoelic injection study, IJs
      harboring phase I resulted in 60% larval mortality at five nematodes/larva, and
      as the number of IJs injected increased, significantly higher larval mortality
      was obtained.

PMID- 8858912
TI  - Peptide RGDS inhibits the fibronectin-enhanced phagocytosis of yeast cells by
      Galleria mellonella hemocytes in vitro.

PMID- 8858913
TI  - Evidence for translational control elements within the 5'-untranslated region of
      GLUT1 glucose transporter mRNA.
AB  - Recent studies have indicated that the blood-brain barrier GLUT1 glucose
      transporter is under post-transcriptional regulation. To begin functional mapping
      of the GLUT1 transcript, in the present investigation we studied the
      translational efficiency of capped full-length synthetic GLUT1 mRNA, and both 5'-
      and 3'-untranslated regions (UTRs) deleted GLUT1 mRNAs. Deletion of 5'- and 5'
      /3'-UTRs markedly reduced the translation efficiency of the human (h) GLUT1
      transcript in the rabbit reticulocyte lysate (RRL), and this effect was not
      modified by addition of microsomes to the translation system. The putative role
      of these hGLUT1 5'-UTR cis-acting elements was studied using the luciferase
      expression vector pGL2. DNA corresponding to the hGLUT1 5'-UTR generated by PCR
      was subcloned at the HindIII site of the pGL2 located upstream of the luciferase
      5'-UTR. Transfection of brain endothelial cultured cells with pGL2 containing
      most of the hGLUT1 5'-UTR (nucleotides 1-171) markedly increased the expression
      of luciferase, and disruption of luciferase-leading sequence with an unrelated
      171-nucleotide fragment decreased its expression. Insertion of nucleotides 1-96
      of the hGLUT1 5'-UTR retained most of the stimulatory effect, and nucleotides 123
      171 produced 64% of maximal induction. On the contrary, clones containing
      nucleotides 79-171 and 154-171 of bGLUT1 5'-UTR had marginal effects on
      luciferase expression. The present data provide evidence suggesting that the 5'
      UTR of the GLUT1 mRNA contains cis-acting elements involved in the translational
      control of the GLUT1 gene in mammalian cells.

PMID- 8858914
TI  - Role of Egr-1 in cholinergic stimulation of phenylethanolamine N
      methyltransferase promoter.
AB  - The effects of the cholinergic agonist carbachol on phenylethanolamine N
      methyltransferase promoter activity and Egr-1 mRNA expression in PC12-derived RS1
      cells were examined to investigate the potential involvement of Egr-1 in the
      neural regulation of phenylethanolamine N-methyltransferase gene expression.
      Carbachol stimulated luciferase expression in cells transfected with a rat
      phenylethanolamine N-methyltransferase promoter-luciferase reporter gene
      construct and also elevated Egr-1 mRNA levels in untransfected cells. Maximum
      induction of Egr-1 mRNA by carbachol was rapid (0.5 h), whereas by comparison,
      peak luciferase activity was delayed (6 h). In addition, carbachol stimulation of
      both luciferase and Egr-1 mRNA expression could be completely inhibited by
      atropine but not hexamethonium. Furthermore, bethanechol but not nicotine could
      mimic the effects of carbachol, indicating that carbachol activation was mediated
      through muscarinic cholinergic receptors. Finally, carbachol failed to stimulate
      luciferase expression in cells transfected with a mutant construct, in which the
      Egr-1 binding element in the phenylethanolamine N-methyl-transferase promoter was
      mutated. These results suggest that carbachol activates the phenylethanolamine N
      methyltransferase promotor through stimulation of Egr-1 expression, and are
      consistent with the potential involvement of Egr-1 in the cholinergic activation
      of the phenylethanolamine N-methyltransferase gene.

PMID- 8858915
TI  - Identification of an octamer-1 transcription factor binding site in the promoter
      of the mouse mu-opioid receptor gene.
AB  - In a previous study we showed that a region from -182 to +10 bp in the mouse mu
      opioid receptor (MOR) promoter exhibited strong promoter activity. To identify
      protein-DNA interactions in this fragment, gel shift and DNase I footprint
      analyses were performed using nuclear extracts from mouse brain and the human
      neuroblastoma cell line, SK-N-SH. Two regions, nucleotide (nt) -121 to -100 and
      nt -42 to -22, were identified as being specific protein binding sites. The
      protein-DNA interaction in the nt -42 to -22 region was characterized in detail
      in this study. Methylation interference analysis of this region showed that
      nuclear protein from SK-N-SH cells contracted nucleotides within the sequence ATG
      CAAAT, which is a binding motif for octamer trans-acting factors. An octamer-1
      (Oct-1)-specific antibody super-shifted the protein-DNA complex in a gel shift
      assay. A UV cross-linking experiment showed that a nuclear protein, whose
      molecular weight is similar to that of the Oct-1 factor, bound to the octamer
      element in the nt -42 to -22 region. Mutagenesis of four base pairs within the
      octamer cis-acting element eliminated the specific protein binding in vitro. When
      the MOR-luciferase reporter construct (-182 to +10 bp) with the same four base
      pairs mutated was transiently transfected into SK-N-SH cells, a 200% increase in
      transcriptional activity was observed. Collectively, these data suggest that Oct
      1 is binding to the octamer motif in the MOR gene and negatively modulating MOR
      gene expression.

PMID- 8858916
TI  - The Lck tyrosine kinase is expressed in brain neurons.
AB  - The lck gene product, p56lck, is a member of the src-related family of protein
      tyrosine kinases. It is known as lymphocyte specific and involved in thymocyte
      development and in the immune response mediated by the T cell receptor. We report
      that the lck gene is also expressed in adult mouse CNS and that brain p56lck is
      similar to the thymus protein. In situ hybridization and immunohistochemistry
      show that the lck gene is expressed in neurons throughout the brain in distinct
      regions, including hippocampus and cerebellum. In primary cultures from fetal
      mouse brain, neuronal cells are immunoreactive to Lck antiserum. This suggests
      that the lck gene product might be involved in a new signal transduction pathway
      in mouse brain.

PMID- 8858917
TI  - Interleukin-6 induces expression of peripherin and cooperates with Trk receptor
      signaling to promote neuronal differentiation in PC12 cells.
AB  - In contrast to the intensively studied nerve growth factor (NGF)-related family
      of cytokines, relatively little is known about the mechanisms of neurotrophic
      activity elicited by the cytokine interleukin-6 (IL-6). We have examined the
      mechanisms of IL-6-induced neuronal differentiation of the pheochromocytoma cell
      line PC12. IL-6 independently induced the expression of peripherin, identifying
      this gene as the first neuronal-specific target of IL-6. However, IL-6 alone
      failed to elicit neurite outgrowth in PC12 cells and instead required low levels
      of Trk/NGF receptor tyrosine kinase activity to induce neuronal differentiation.
      The cooperating Trk signal could be provided by either overexpression of Trk or
      exposure to low concentrations of NGF. IL-6 also functioned cooperatively with
      basic fibroblast growth factor to promote PC12 differentiation. IL-6 and Trk/NGF
      synergized in enhancing tyrosine phosphorylation of the Erk-1 mitogen-activated
      protein kinase and in activating expression of certain NGF target genes. NGF also
      induced expression of the gp80 subunit of the IL-6 receptor, providing another
      potential mechanism of cooperativity between NGF and IL-6 signaling. We propose
      that IL-6 functions as an enhancer of NGF signaling rather than as an autonomous
      neuronal differentiation signal. Moreover, our results demonstrate that a Trk
      receptor-specific cellular response can be achieved in the absence of NGF through
      amplification of its basal signaling activity by the IL-6 receptor system.

PMID- 8858918
TI  - Glutathione content as an indicator for the presence of metabolic pathways of
      amino acids in astroglial cultures.
AB  - The intracellular content of glutathione in astroglia-rich primary cultures
      derived from the brains of newborn rats was measured to be 32.1 +/- 5.4 nmol/mg
      of protein. During a 24-h incubation in a minimal medium lacking amino acids and
      glucose, the content of glutathione in these cultures was reduced to 52% of the
      original content. On refeeding of glucose, glutamate, glycine, and cysteine,
      glutathione was resynthesized. A maximal content of glutathione was found 4 h
      after refeeding, exceeding the amount of glutathione of untreated cultures by
      72%. Maximal glutathione synthesis was observed only if glutamate, cysteine, and
      glycine were present. If successively each one of these amino acids was made
      limiting for the synthesis of glutathione, half-maximal contents of glutathione
      were found at 0.2 mM glutamate, 20 microM cysteine, or 10 microM glycine.
      Replacement of glutamate or glycine by other amino acids revealed the potential
      of astroglial cells to convert glutamine, aspartate, asparagine, proline, and
      ornithine into glutamate, and serine into glycine. These results demonstrate that
      the concentration of intracellular glutathione can serve as an indicator for the
      presence of metabolic pathways of amino acids in cultured cells.

PMID- 8858919
TI  - Increased superoxide dismutase activity improves survival of cultured postnatal
      midbrain neurons.
AB  - Copper/zinc superoxide dismutase (Cu/Zn-SOD) is a major free radical scavenging
      enzyme. Increased Cu/Zn-SOD activity protects cells against oxidative stress
      mediated by different mechanisms. However, there is also in vitro and in vivo
      evidence that, in the absence of abnormal oxidative stress, chronic increased
      Cu/Zn-SOD activity is detrimental to living cells. To address this issue, we
      examined the fate of mature midbrain neurons from transgenic mice expressing
      human Cu/Zn-SOD and from their nontransgenic littermates. Midbrain from
      transgenic pups had about threefold higher Cu/Zn-SOD activity than that from
      nontransgenic pups. Virtually all transgenic neurons were strongly immunoreactive
      for human Cu/Zn-SOD protein in their cell bodies and processes. The number of
      midbrain neurons decreased over time in both transgenic and nontransgenic
      cultures, but to a significantly smaller extent in the transgenic cultures.
      Postnatal midbrain neurons died by either necrosis or apoptosis, and increased
      Cu/Zn-SOD activity attenuated both forms of cell death. Furthermore, increased
      Cu/Zn-SOD activity better prevented the loss of dopaminergic neurons than
      GABAergic neurons. We also found that neuronal processes were dramatically denser
      in transgenic cultures than in nontransgenic cultures. These results indicate
      that chronic increased Cu/Zn-SOD activity does not appear to be detrimental, but
      rather promotes cell survival and neuronal process development in postnatal
      midbrain neurons, probably by providing more efficient detoxification of free
      radicals. They also show that increased Cu/Zn-SOD activity does not seem to play
      a critical role in determining the mode of cell death in this culture system.

PMID- 8858920
TI  - GT3 synthesis in the proximal Golgi occurs in a compartment different from those
      for GD3 and GM3 synthesis.
AB  - Previous studies from this laboratory have shown that synthesis of GT3, the
      precursor of c series gangliosides, occurs in proximal Golgi compartments, as has
      been shown for the synthesis of GM3 and GD3, the precursors of a and b series
      gangliosides, respectively. In this work we studied whether the synthesis of GM3,
      GD3, and GT3 occurs in the same or in different compartments of the proximal
      Golgi. For this, we examined in retina cells (a) the effect of monensin, a sodium
      ionophore that affects mostly the trans Golgi and the trans Golgi network
      function, on the metabolic labeling of glycolipids from [3H]Gal by cultured cells
      from 7- and 10-day chick embryos and (b) the labeling in vitro of endogenous
      glycolipids of Golgi membrane preparations from 7-day embryos incubated with UDP
      [3H]Gal. In (a), 1 microM monensin produced a twofold accumulation of radioactive
      glucosylceramide and a decrease to approximately 50 and 20% of total ganglioside
      labeling in 7- and 10-day cells, respectively. At both ages, monensin produced a
      threefold accumulation of radioactive GM3 and an inhibition of > 90% of GT3, GM1,
      GD1a, and GT1b synthesis. GD3 synthesis was inhibited approximately 30 and 70%,
      respectively, in 7- and 10-day cells. In (b), > 80% of the [3H]Gal was
      incorporated into endogenous glucosylceramide to form radioactive
      lactosylceramide. About 90% of [3H]Gal-labeled lactosylceramide was converted
      into GM3, and most of this in turn into GD3 when unlabeled CMP-NeuAc was also
      present in the incubation system. Under the same conditions, however, < 5% of
      labeled GD3 was converted into GT3. Golgi membranes incubated with CMP-[3H]NeuAc
      incorporated approximately 20% of [3H]NeuAc into endogenous GT3, and this
      percentage was not affected by 1 microM monensin. These results indicate that
      synthesis of GT3 is carried out in a compartment of the proximal Golgi different
      from those for lactosylceramide, GM3, and GD3 synthesis. Results from the
      experiments with monensin point to the cis/medial Golgi as the main compartment
      for coupled synthesis of lactosylceramide, GM3, and GD3 and to the trans Golgi as
      the main compartment for synthesis of GT3.

PMID- 8858921
TI  - Up-regulation of functional voltage-dependent sodium channels by insulin in
      cultured bovine adrenal chromaffin cells.
AB  - Treatment of cultured bovine adrenal chromaffin cells with 100 nM insulin raised
      [3H]saxitoxin ([3H]-STX) binding in a time-dependent manner (t1/2 = 26 h).
      Insulin (100 nM for 4 days) increased the Bmax of [3H]STX binding by 49% without
      changing the KD value and also augmented the maximal influx of 22Na+ due to 560
      microM veratridine by 39% without altering the EC50 value of veratridine. The
      stimulatory effect of insulin on 22Na+ influx was concentration-dependent with an
      EC50 of 3 nM, whereas insulin-like growth factor (IGF)-I had little effect at 1
      nM. Ptychodiscus brevis toxin-3 allosterically potentiated veratridine (100
      microM)-induced 22Na+ influx by approximately twofold in both insulin-treated
      cells and untreated cells. Veratridine-induced 45Ca2+ influx via voltage
      dependent Ca2+ channels and catecholamine secretion were also enhanced by insulin
      treatment, whereas insulin did not alter nicotine-induced 22Na+ influx via the
      nicotinic receptor-ion channel complex and high-K+ (direct activation of voltage
      dependent Ca2+ channels)-induced 45Ca2+ influx. Stimulatory effects of insulin on
      [3H]-STX binding and veratridine-induced 22Na+ influx were nullified by
      simultaneous treatment with either 5,6-dichlorobenzimidazole riboside, an
      inhibitor of RNA synthesis, or cycloheximide, an inhibitor of protein synthesis,
      whereas insulin treatment did not appreciably increase the level of mRNA encoding
      the Na+ channel alpha-subunit. These results suggest that the binding of insulin
      to insulin (but not IGF-I) receptors mediates the up-regulation of functional Na+
      channel expression at plasma membranes; this up-regulation may be due, at least
      in part, to the de novo synthesis of an as yet unidentified protein(s).

PMID- 8858922
TI  - Endothelins induce Fos expression in neurons and glia in organotypic cultures of
      rat cerebellum.
AB  - Endothelins (ETs) and their receptors are present in high levels in the brain and
      have been proposed to act as neuromodulators or neurotransmitters. However,
      neither their role nor their precise mechanism of action in the brain is
      understood. In this study, c-fos expression was used as a marker of neuronal
      activation in organotypic cultures of rat cerebellum. ETs induced Fos protein
      expression in both granule cells and glia but not in Purkinje cells. Granule
      cells and glia were both very sensitive to ETs, but different receptor subtypes
      appeared to be involved, because granule cells did not respond to ET-3. However,
      they did respond to the ETB-selective agonist BQ3020, suggesting the possible
      existence of a novel neuronal ETB-like receptor. The induction of Fos in granule
      cells was independent of extracellular calcium ion concentration, but the
      ryanodine receptor antagonist dantrolene significantly inhibited the response to
      ETs, suggesting that the mobilisation of calcium ions from intracellular stores
      is important. These data support previous evidence that ETs act directly on
      neurones and show that the intracellular pathways after ET receptor activation
      are complex. It appears likely that ETs play an important neuromodulatory role in
      the cerebellum.

PMID- 8858923
TI  - Actions of neurotoxic beta-amyloid on calcium homeostasis and viability of PC12
      cells are blocked by antioxidants but not by calcium channel antagonists.
AB  - The fragment of beta-amyloid comprised of amino acids 25-35 induces a rapid,
      concentration-dependent increase in cytosolic free calcium levels in suspensions
      of PC12 neuronal cells. This action of beta-amyloid 25-35 is not altered by
      pretreatment with the calcium channel blockers nifedipine or cobalt, with the
      depleter of intracellular calcium stores cyclopiazonic acid, or with the
      phospholipase C inhibitor neomycin. However, the effects of beta-amyloid 25-35 on
      cytosolic free calcium are absent in calcium-free buffer and are blocked by the
      antioxidant lazaroid U-83836E and by vitamin E. beta-Amyloid 25-35 is also
      neurotoxic and produces a concentration-dependent reduction in the viability of
      PC12 cells in culture. The neurotoxic action of beta-amyloid is blocked by U
      83836E and vitamin E but not by nifedipine or cobalt. These data indicate that
      both the disruption of calcium homeostasis and the reduction of cell viability
      produced by beta-amyloid in PC12 cells are mediated by free radical-based
      processes.

PMID- 8858924
TI  - Signaling pathway downstream of GABAA receptor in the growth cone.
AB  - The growth cone is responsible for axonal elongation and pathfinding by
      responding to various modulators for neurite growth, including neurotransmitters,
      although the sensor mechanisms are not fully understood. Among neurotransmitters,
      GABA is most likely to demonstrate activity in vivo because GABA and the GABAA
      receptor appear even in early stages of CNS development. We investigated the
      GABAA receptor-mediated signaling pathway in the growth cone using isolated
      growth cones (IGCs). Both the GABAA binding site and the benzodiazepine
      modulatory site were enriched in the growth cone membrane. In the intact IGC,
      GABA induced picrotoxin-sensitive Cl- flux (not influx but efflux) and increased
      the intracellular Ca2+ concentration in a picrotoxin- and verapamil-sensitive
      manner. Protein kinase C (PKC)-dependent phosphorylation of two proteins
      identified as GAP-43 and MARCKS protein was enhanced in the intact IGC stimulated
      by GABA, resulting in the release of MARCKS protein and GAP-43 from the membrane.
      Collectively, our results suggest the following scheme: activation of the
      functional GABAA receptor localized in the growth cone membrane-->Cl- efflux
      induction through the GABAA-associated Cl- channel-->Ca2+ influx through an L
      type voltage-sensitive Ca2+ channel-->Ca(2+)-dependent phosphorylation of GAP-43
      and MARCKS protein by PKC.

PMID- 8858925
TI  - Exposure of astrocytes to thrombin reduces levels of the metabotropic glutamate
      receptor mGluR5.
AB  - Thrombin is one of the first regulatory molecules present at sites of CNS trauma
      or injury. Exposure of neuronal and glial cells to thrombin produces potent
      morphological as well as cytoprotective and cytotoxic effects, but little is
      known about how this important modulator affects neurotransmitter signaling. In
      astrocyte cultures that have been morphologically differentiated by exposure to
      transforming growth factor-alpha, addition of thrombin induced a retraction of
      astrocytic processes and suppressed the stimulation of phosphoinositide
      hydrolysis by the selective metabotropic glutamate receptor (mGluR) agonist 1
      aminocyclopentane-1S,3R-dicarboxylic acid. In addition to the suppression of
      phosphoinositide hydrolysis, thrombin treatment produced a corresponding
      reduction in level of mGluR5 mRNA as demonstrated with ribonuclease protection
      assay and reduced content of mGluR5 receptor protein as seen with western
      blotting. In contrast, thrombin exposure up-regulated astrocyte beta-actin mRNA
      levels. A synthetic hexapeptide with a sequence corresponding to the amino
      terminus of the thrombin receptor's tethered ligand also mimicked the ability of
      thrombin to suppress mGluR5 levels and to increase beta-actin mRNA content,
      suggesting that these effects of thrombin are mediated by proteolytically
      activated cell surface thrombin receptors. Thrombin's suppressive effect on
      mGluR5 was resistant to pretreatment with pertussis toxin or various protein
      kinase and protein phosphatase inhibitors. However, the serine/threonine protein
      kinase inhibitor H-7 did prevent thrombin-induced reversal of astrocyte
      stellation and induction of beta-actin mRNA levels, indicating that these effects
      of thrombin involve a signaling pathway distinct from the one that mediates the
      suppressive effects of thrombin on mGluR5.

PMID- 8858926
TI  - Ethanol inhibits basic fibroblast growth factor-mediated proliferation of C6
      astrocytoma cells.
AB  - Early ethanol exposure alters the proliferative activity of glial and neuronal
      precursors in the developing CNS. The present study tests the hypothesis that
      ethanol-induced alterations in cell proliferation result from interference with
      growth factors. An in vitro model of astroglia (C6 astrocytoma cells) was used to
      study the effects of ethanol on proliferation mediated by basic fibroblast growth
      factor (bFGF). bFGF stimulated the proliferation of C6 cells. This bFGF-enhanced
      proliferation was evident by increases in total cell number, DNA synthesis (as
      measured by [3H]thymidine incorporation), and the number of cells that took up
      bromodeoxyuridine. A synthetic peptide that specifically blocked the binding of
      bFGF to its high-affinity receptor completely abolished the proliferation
      promoting effect of bFGF. The action of another mitogen for C6 cells, insulin
      like growth factor-1, was not affected by this peptide. Therefore, the bFGF
      stimulated proliferation was mediated through a specific bFGF receptor. Ethanol
      inhibited bFGF-mediated proliferation in a concentration-dependent manner.
      Ethanol concentrations of 100 and 200 mg/dl partially inhibited bFGF-mediated
      proliferation (by 58 and 74%, respectively), whereas concentrations of > or = 400
      mg/dl completely abolished the growth-stimulating effect of bFGF. Our data show
      that ethanol alters proliferative activity of C6 cells by disrupting the action
      of bFGF. The target of ethanol neurotoxicity is a receptor-mediated activity.
      bFGF can affect cell proliferation by a non-receptor-mediated intracellular
      pathway, but ethanol does not have an impact on this pathway.

PMID- 8858927
TI  - Initial processing of human proenkephalin in bovine chromaffin cells.
AB  - The opioid peptide precursor preproenkephalin (PPE) contains seven enkephalin
      sequences and is synthesized by epinephrine-producing adrenal chromaffin cells
      and various peripheral and central neurons. After removal of its signal peptide,
      PPE undergoes processing at dibasic amino acid sites to yield its final opioid
      products-Met-enkephalin, Leu-enkephalin, and various larger, enkephalin
      containing peptides. Processing of PPE was examined in bovine chromaffin cells
      using a plasmid containing the human PPE (hPPE) cDNA under the control of the
      cytomegalovirus immediate early enhancer/promoter. Following transfection of this
      hPPE-containing plasmid into bovine chromaffin cells, several proenkephalin
      immunoreactive bands were observed on western blots with monoclonal antibodies
      that recognize human, but not bovine, proenkephalin sequences. The pattern of
      hPPE-derived peptides observed was similar to that of bovine PPE processing
      products. A series of recombinant plasmids containing mutations in the hPPE
      sequence at putative processing sites was then constructed. Conversion of Lys-Lys
      and Lys-Arg sequences to Lys-Gln and of Arg-Arg to Arg-Gln altered initial hPPE
      processing at only three of the putative processing sites. When hPPE cDNA
      containing mutations at all of these initially processed sites was expressed, one
      or more alternative processing sites were revealed. These data suggest the
      importance of structural features in addition to the dibasic sequences that limit
      the processing of proenkephalin.

PMID- 8858928
TI  - Effects of fructose-1,6-bisphosphate on glutamate release and ATP loss from rat
      brain slices during hypoxia.
AB  - Fructose-1,6-bisphosphate (FBP), an intermediate of glucose metabolism, is
      neuroprotective in brain hypoxia or ischemia. Because the mechanisms for this
      protection are not clear, we examined the effects of FBP on two important events
      in brain ischemia, i.e., loss of ATP and release of the excitatory
      neurotransmitter glutamate. Glutamate release from cortical brain slices was
      measured fluorometrically (glutamate dehydrogenase-catalyzed conversion of
      glutamate to alpha-ketoglutarate) during hypoxia (PO2 15 mm Hg) or hypoxia plus
      100 microM cyanide. FBP (3.5 mM, with glucose 20 mM) reduced glutamate release
      during hypoxia by 55% and during hypoxia/cyanide by 46% (p < 0.005), and
      prevented a significant fall in [ATP]. [ATP] was maintained in oxygenated glucose
      free conditions with 20 but not 3.5 mM FBP, and fell to < 20% of normal with
      hypoxia. Despite the drop in [ATP], 3.5 or 20 mM FBP without glucose decreased
      hypoxia-evoked glutamate release. We conclude (1) FBP present without glucose
      preserves normal [ATP] only when oxygen is available, suggesting limited uptake
      and metabolism; and (2) FBP decreases hypoxia-evoked glutamate release by
      processes independent of [ATP]. These results suggest protective actions of FBP
      that are separate from augmentation of anaerobic energy production, as previously
      proposed.

PMID- 8858929
TI  - Adenosine A1 receptors in cultured cerebellar granule cells: role of endogenous
      adenosine.
AB  - Adenosine A1 receptors as well as other components of the adenylate cyclase
      system have been studied in cultured cerebellar granule cells. No significant
      changes in adenosine A1 receptor number, assayed by radioligand binding in intact
      cells, were detected from 2 days in vitro (DIV) until 7 DIV. Nevertheless, a
      decline in this parameter was detected at 9 DIV. The steady-state levels of alpha
      Gg and alpha-Gi, detected by immunoblotting, showed similar profiles, increasing
      from 2 to 5 DIV and decreasing afterward. Forskolin-stimulated adenylate cyclase
      levels also showed an increase until 5 DIV, decreasing at 7 and 9 DIV. The
      adenosine A1 receptor analogue cyclopentyladenosine (CPA) was able to inhibit
      cyclic AMP accumulation at 2, 5, and 7 DIV but failed to do so at 9 DIV. This
      inhibition was prevented by the specific adenosine A1 receptor antagonist 8
      cyclopentyl-1,3-dipropylxanthine. The presence of adenosine deaminase in the
      culture increased adenosine A1 receptor number during the period studied and
      induced recovery of the inhibitory effect of CPA, lost after 7 DIV. These data
      suggest that functional expression of adenosine A1 receptors and the other
      components of the adenylate cyclase system is subjected to regulation during the
      maturation of cultured cerebellar granule cells and demonstrates a key role for
      endogenous adenosine in the process.

PMID- 8858930
TI  - Guanine nucleotide regulatory proteins, Gq and Gi1/2, mediate platelet-activating
      factor-stimulated phosphoinositide metabolism in immortalized hippocampal cells.
AB  - Platelet-activating factor (PAF) may be a neuromodulator involved in neural cell
      differentiation, cerebral inflammation, and ischemia. The PAF receptor is a
      member of the G protein-coupled receptor superfamily. In the present study, we
      sought to define the specific G protein(s) that mediate PAF-stimulated
      phosphoinositide (PI) metabolism in an immortalized hippocampal cell line,
      HN33.11. PAF increased the production of 3H-labeled inositol phosphates (IPs)
      with EC50 values of 1.2-1.5 nM. The effect of PAF on 3H-IPs formation was
      completely blocked by the PAF antagonist BN 50739 at a concentration of 300 nM.
      Pertussis toxin pretreatment attenuated PAF-stimulated 3H-IPs production by 20
      30% (p < 0.05). Consistent with a role for Gi1/2 in this response, antiserum
      against G alpha i1/2 blocked the response to a similar degree. Pretreatment of
      permeabilized cells with G alpha q/11 antiserum attenuated the response by 70% (p
      < 0.05), suggesting a role for Gq/11 in mediating the PAF response in this cell
      line. Stimulation with PAF increased [alpha-32P]-GTP binding to both G alpha q
      and G alpha i1/2 proteins. Moreover, specific [3H]PAF binding sites
      coprecipitated with G alpha q and G alpha i1/2 proteins. The results suggest that
      PAF-stimulated PI metabolism in HN33.11 cells is mediated by both Gq and Gi1/2
      proteins.

PMID- 8858931
TI  - Formation of D-serine from L-phosphoserine in brain synaptosomes.
AB  - Although glycine has been assumed to be the sole endogenous coagonist at NMDA
      associated glycine receptors, recent descriptions of endogenous D-serine in the
      brain indicate that this assumption is probably not valid. D-Serine is a
      stereospecific agonist of the NMDA-associated glycine receptor, with an affinity
      equal to or greater than that of glycine but with no affinity for the strychnine
      sensitive glycine receptor. In the current studies, we assessed the levels and
      metabolic sources of D-serine in rat neocortical synaptosomal preparations.
      Previous studies have demonstrated that CNS serine and glycine are synthesized de
      novo primarily via a phosphorylated pathway, originating with the glycolytic
      intermediate phosphoglycerate. The rate-limiting step in the synthesis of serine
      is the hydrolysis of phosphoserine by phosphoserine phosphatase (EC 3.1.3.3). In
      synaptosomal preparations we have demonstrated high endogenous levels of D-serine
      and the uptake of L-phosphoserine along with its hydrolysis to both L-serine and
      D-serine, which are preferentially released into the medium. Experiments with
      both intact and lysed synaptosomal preparations demonstrated hydrolysis of D
      phosphoserine to only D-serine and inhibition of hydrolysis by the phosphoserine
      phosphatase inhibitor 2-amino-3-phosphonopropionic acid (AP3). The lack of
      stereospecificity for synaptosomal hydrolysis of phosphoserine and the inhibitory
      actions of AP3 are consistent with the presence of phosphoserine phosphatase in
      synaptosomes and further indicate that epimerization of serine can occur during
      or subsequent to the hydrolysis of L-phosphoserine but not D-phosphoserine. In
      conclusion, these studies demonstrate that phosphoserine phosphatase may be an
      important enzyme in regulating the steady-state levels of D-serine in neocortical
      synaptosomes.

PMID- 8858932
TI  - Oligodendroglial signal transduction systems are regulated by neuronal contact.
AB  - Previous reports indicate that oligodendrocytes express signaling systems
      activated by classical neurotransmitters. Several signaling systems linked to
      mobilization of intracellular calcium have been demonstrated, and some of these
      are developmentally lost in vitro and in vivo. The experiments described here use
      oligodendrocyte-neuron cocultures to examine the effects of neuronal contact on
      the expression of these signaling pathways. Neonatal rat cerebral
      oligodendrocytes in contact with dorsal root ganglia (DRG) neurites responded to
      bath application of histamine, ATP, carbachol, glutamate, or bradykinin with
      increases in intracellular Ca2+ concentration. Similar results were obtained in
      coculture with superior cervical ganglia neurons. Preventing neuronal contact by
      transection of DRG neurites significantly reduced the percentage of
      oligodendrocytes responsive to each ligand, with the exception of bradykinin
      responsiveness, which was unaffected. Oligodendroglia isolated from adult rat
      spinal cord were also examined for responsiveness to these neuroligands. Few
      isolated adult oligodendroglia were responsive to these ligands, and coculture
      with DRG neurons failed to restore responsiveness. Neuroligand responsiveness was
      not induced in oligodendrocytes maintained 8 days in purified culture before
      establishment of cocultures. A significant reduction in the number of neuroligand
      responsive oligodendroglia was noted for histamine, carbachol, glutamate, and ATP
      after including tetrodotoxin for the final 6 days of coculture. These results
      suggest that both neuronal contact and neuronal activity contribute to the
      maintenance of functional neurotransmitter-activated signaling pathways coupled
      to mobilization of intracellular calcium in oligodendrocytes.

PMID- 8858933
TI  - High level expression of the NMDAR1 glutamate receptor subunit in electroporated
      COS cells.
AB  - The rat N-methyl-D-aspartate (NMDA) glutamate receptor subunit NR1-1a was
      transiently expressed in COS cells using the technique of electroporation, which
      was fivefold more efficient than the calcium phosphate precipitation method of
      transfection. The glycine site antagonist 5,7-[3H]dichlorokynurenic acid labeled
      a single high-affinity site (KD = 29.6 +/- 6 nM; Bmax = 19.4 +/- 1.6 pmol/mg of
      protein) in membranes derived from COS cells electroporated with NR1-1a. In
      contrast to previous reports using transiently transfected human embryonic kidney
      293 cells, binding of the noncompetitive antagonist (+)-5-[3H]methyl-10,11
      dihydro-5H-dibenzo[a,d]-cyclohepten-5, 10-imine ([3H]MK-801) was not detected in
      NR1-1a-transfected COS cells. Although immunofluorescent labeling of
      electroporated COS cells demonstrated that the NR1-1a protein appears to be
      associated with the cell membrane, neither NMDA nor glutamate effected an
      increase in intracellular calcium concentration in fura-2-loaded cells,
      suggesting that homomeric NR1-1a receptors do not act as functional ligand-gated
      ion channels. Therefore, COS cells appear to differ from Xenopus oocytes with
      respect to the transient expression of functional homomeric NR1 receptors.
      Although expression of NR1-1a is sufficient to reconstitute a glycine binding
      site with wild-type affinity for antagonists in COS cells, recombinant homomeric
      NR1-1a receptors do not display properties that are characteristic of native NMDA
      receptors, such as permeability to Ca2+ and channel occupancy by MK-801, when
      expressed in this mammalian cell line.

PMID- 8858934
TI  - Phorbol esters but not the cholinergic agonists oxotremorine-M and carbachol
      increase release of the amyloid precursor protein in cultured rat cortical
      neurons.
AB  - Conventional secretory processing of the amyloid precursor protein is
      nonamyloidogenic, releasing carboxyl-terminus-truncated amyloid precursor protein
      derivatives while cleaving the amyloid beta-peptide within its sequence.
      Alternative processing routes are potentially amyloidogenic, yielding the amyloid
      beta-peptide segment intact. In continuous cell lines, secretory processing of
      the amyloid precursor protein is regulated by both protein kinase C and
      muscarinic receptor stimulation. However, the first and second messenger systems
      that regulate amyloid precursor protein release in central neurons are still
      under investigation. In the present investigation, we examined whether or not
      first and second messengers of cholinergic neurotransmission increase production
      of soluble derivatives of the amyloid precursor protein in primary cultures of
      rat cortical neurons. Activation of protein kinase C by the phorbol esters
      phorbol 12,13-dibutyrate and phorbol 12-myristate 13-acetate increased production
      of the soluble form of the amyloid precursor protein dramatically. In contrast,
      activation of muscarinic receptors by oxotremorine-M or carbachol did not result
      in a significant increase in amyloid precursor protein release. Similarly,
      chemically induced depolarization using 35 mM KCl did not alter production of
      soluble amyloid precursor protein derivatives. Our data suggest that although
      protein kinase C stimulation plays an important role in regulating release of the
      amyloid precursor protein, cholinergic neurotransmission does not regulate its
      release in cultured rat cortical neurons.

PMID- 8858935
TI  - Acidic fibroblast growth factor and catecholamines synergistically up-regulate
      tyrosine hydroxylase activity in developing and damaged dopamine neurons in
      culture.
AB  - Our previous studies indicate that, in certain non-catecholamine (CA) neurons,
      expression of the gene for the CA biosynthetic enzyme tyrosine hydroxylase (TH)
      can be initiated by the obligatory interaction of acidic fibroblast growth factor
      (aFGF) and a CA activator. In this study, we sought to determine whether these
      same differentiation factors also play a role in regulating existing TH
      expression in CA neurons. Thus, the effects of exogenous aFGF and CAs on TH were
      studied in developing or toxin-damaged dopamine (DA) neurons from the embryonic
      day 15 rat ventral midbrain, where it was likely to be at physiologically low
      levels. Cultures were incubated with various concentrations of aFGF, DA, or aFGF
      and DA. Some cultures were first damaged with 2.5 microM 1-methyl-4
      phenylpyridinium. In developing DA neurons, an 80% increase in TH activity was
      found only after co-treatment with aFGF (100 ng/ml) and DA (1 microM) or other
      monoamines. Likewise, in damaged DA neurons, aFGF and DA reversed the 50% loss in
      TH activity caused by toxin. This was observed within 4 h of treatment and was
      not associated with changes in the number or appearance of DA neurons, suggesting
      a biochemical rather than a trophic effect. Pretreatment with protein or RNA
      synthesis inhibitors eliminated the increase. In PC12 cells, where TH is highly
      expressed, activity was unaltered by treatment. We conclude that the aFGF and CAs
      may be involved in not only the initiation but also the regulation of TH.

PMID- 8858936
TI  - Cerebral energy metabolism during severe ischemia of varying duration and
      following reperfusion.
AB  - Changes in cerebral cortical adenine nucleotide and adenosine levels during 10-,
      20-, or 40-min periods of four-vessel occlusion producing cerebral ischemia in
      rats and reperfusions of 10, 45, or 90 min were determined to evaluate the
      effects of ischemia duration on mitochondrial function. Substantial recovery was
      evident following 10 or 20 min of cerebral ischemia but not, however, after a 40
      min period of ischemia. A secondary decline in the cortical levels of ATP became
      evident following 40 min of cerebral ischemia and 90 min of reperfusion. Longer
      periods of ischemia may be associated with a loss of adenosine, limiting the
      resynthesis of ATP during reperfusion. A separate group of rats, resuscitated
      with 100% O2, demonstrated a more rapid recovery of mitochondrial function
      compared with animals that received room air during reperfusion following 20 min
      of cerebral ischemia. No detrimental effects of 100% O2 were observed during the
      90-min period of reperfusion, indicating that 100% O2 does not promote early
      mitochondrial dysfunction.

PMID- 8858937
TI  - Effect of long-term treatment with selective monoamine oxidase A and B inhibitors
      on dopamine release from rat striatum in vivo.
AB  - Acute inhibition of monoamine oxidase B (MAO-B) in the rat does not affect
      striatal dopamine (DA) metabolism, but chronic MAO-B inhibition with deprenyl has
      been reported to increase the release of striatal DA, as shown using in vitro
      techniques. To see whether chronic MAO-B inhibition also causes an increase in DA
      release in vivo, rats were treated for 21 days with either deprenyl (0.25 mg/kg),
      TVP-1012 [R(+)-N-propargyl-1-aminoindan mesylate; 0.05 mg/kg], an irreversible
      inhibitor of MAO-B that is not metabolized to amphetamines, clorgyline (0.2
      mg/kg), or saline (all doses once daily by subcutaneous injection). Concentric 4
      mm-long microdialysis probes were implanted in the left striatum under
      pentobarbital/chloral hydrate anesthesia on day 21, and microdialysate DA, 3,4,
      dihydroxyacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenyl acetic acid (HVA)
      were determined in the conscious animals on day 22. Baseline levels of DA were as
      follows: control, 0.34 +/- 0.04 (n = 13); deprenyl, 0.88 +/- 0.10 (n = 8, p <
      0.01); TVP-1012, 0.94 +/- 0.20 (n = 7, p < 0.01); clorgyline, 0.90 +/- 0.12 (n =
      7, p < 0.01) pmol/20 min. Levels of DOPAC and HVA were reduced only in the
      clorgyline-treated group. The incremental release of DA induced by depolarizing
      concentration of K+ (100 mM bolus of KCl in perfusate) was significantly greater
      in clorgyline- and deprenyl-treated rats and elevated (nonsignificantly) in TVP
      1012-treated rats. Chronic treatment with the MAO-B inhibitors reduced striatal
      MAO-B activity by 90%, with 15% (TVP-1012) or 40% (deprenyl) inhibition of MAO-A.
      Clorgyline inhibited MAO-A by 95%, with 30% inhibition of MAO-B. A single dose of
      deprenyl (0.25 mg/kg, 24 h before microdialysis) had no significant effect on
      striatal efflux of DA. The results show that DA metabolism was reduced only by
      clorgyline, whereas neuronal release of DA was enhanced by both MAO-A and MAO-B
      inhibitors on chronic administration. The enhanced DA release by chronic MAO-B
      inhibition does not appear to be dependent on production of amphetamine-like
      metabolites of the inhibitor. Possible mechanisms for the release-enhancing
      effect of the MAO-B inhibitors include elevation in levels of endogenous beta
      phenylethylamine, or an inhibition of DA reuptake, which develops only on chronic
      administration, because both deprenyl and TVP-1012 have only very weak effects on
      amine uptake in acute experiments.

PMID- 8858938
TI  - Preferential vulnerability of nucleus accumbens dopamine binding sites to low
      level lead exposure: time course of effects and interactions with chronic
      dopamine agonist treatments.
AB  - This study examined the hypotheses that low-level lead (Pb) exposure would
      increase dopamine (DA) binding sites, would do so preferentially in nucleus
      accumbens, and that such effects would be modified by concurrent DA agonist
      treatment. D1-like and D2-like binding sites and the dopamine transporter (DT)
      were measured autoradiographically in caudate-putamen and nucleus accumbens of
      rats exposed from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions with
      or without concurrent chronic intermittent intraperitoneal injections of the D1
      like agonist SKF 82958 or the DA agonist apomorphine after 2 weeks (no
      injections), 8 months, or 12 months of Pb exposure. Pb selectively decreased DA
      binding in nucleus accumbens. Decreases in D2-like and DT sites were sustained
      across the 12-month exposure, whereas D1-like sites evidenced recovery at 12
      months. Chronic intermittent DA agonist treatments reversed these effects of Pb
      in nucleus accumbens, restoring receptor and DT binding levels to normal, despite
      decreasing binding sites of non-Pb-treated rats. These studies implicate
      increased DA availability as a mechanism of Pb-induced DA system changes. They
      also raise the possibility that Pb exposure could serve as a predisposing factor
      in neurodegenerative diseases associated with DA system dysfunction or could
      alter the course of DA-based therapeutic treatments.

PMID- 8858939
TI  - Cyclothiazide unmasks an AMPA-evoked release of arachidonic acid from cultured
      striatal neurones.
AB  - The joint, but not independent, activation of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA) and metabotropic glutamate receptors induces
      liberation of arachidonic acid from cultured mouse striatal neurones. We examined
      whether blocking AMPA receptor desensitisation with cyclothiazide would modify
      this response. Cyclothiazide strongly potentiated the combined AMPA/(1 S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (ACPD)-evoked release of arachidonic acid
      (EC50 of approximately 7 microM) but did not modulate the basal, ACPD, or NMDA
      response. The enhanced liberation of arachidonic acid, observed in the presence
      of cyclothiazide, was due to the appearance of a genuine AMPA response that was
      independent of an associative activation of metabotropic receptors. The
      potentiated and nonpotentiated AMPA responses were inhibited by both competitive
      [2,3-di-hydroxy-6-nitro-7-sulphamoylbenzo (f) quinoxaline] and 2,3-benzodiazepine
      noncompetitive (GYKI 53655 and GYKI 52466) receptor antagonists. Cyclothiazide
      was equally effective at potentiating the AMPA response in either the presence or
      absence of glucose, suggesting that the increased glutamate-evoked arachidonic
      acid release observed in these cells under conditions of glucose deprivation is
      not due to reduced AMPA receptor desensitisation. The enhanced liberation of
      arachidonic acid measured in the presence of cyclothiazide appeared to result
      from a large (fourfold) elevation of the AMPA-induced increase in intracellular
      calcium level. Therefore, an AMPA-evoked mobilisation of arachidonic acid could
      potentially contribute to non-NMDA receptor-mediated neurotoxicity, which has
      been observed in neuronal cells in the presence of cyclothiazide.

PMID- 8858940
TI  - Accumulation of DNA damage in aging neurons occurs through a mechanism other than
      apoptosis.
AB  - Two biochemical strategies using nick translation-type of incubation and terminal
      tranferase-catalyzed reaction were used to assess single-(SSB) and double-strand
      (DSB) breaks in DNA of permeabilized neurons isolated from young, adult, and old
      rat cerebral cortex. Both SSBs and DSBs accumulate with age. On prior treatment
      of neuronal cells with 1 mM glutamate or 50 microM N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), more extensive damage was seen at all ages, with the old
      neurons suffering maximal damage. When neuronal DNA was subjected to agarose
      electrophoresis, increasingly diffused bands were seen with age in normally aging
      neurons. However, a typical nucleosomal ladder, characteristic of apoptosis, was
      seen only when the cells were exposed to either glutamate or MNNG irrespective of
      the age of the neurons. Furthermore, this apoptotic fragmentation of DNA was
      prevented by prior treatment of the cells with either cycloheximide or
      aurintricarboxylic acid, indicating that both glutamate and MNNG induce
      programmed cell death. Fluorescence microscopic observation of glutamate- and
      MNNG-treated neurons after acridine orange staining revealed a high degree of
      staining and marked condensation of nuclear DNA. On the other hand, no such
      phenomenon was observed in normally aging neurons either histologically or in
      biochemical assays of damage. It is concluded that both glutamate and MNNG induce
      programmed cell death in neurons independent of age and that accumulation of DNA
      damage in naturally aging neurons occurs through a process other than that of
      apoptosis.

PMID- 8858941
TI  - Differential axonal transport of soluble and insoluble tau in the rat sciatic
      nerve.
AB  - Axonal transport of microtubule-associated protein tau was studied in the motor
      fibers of the rat sciatic nerve 1-4 weeks after labeling of the spinal cord with
      [35S]methionine. As 60-70% of low molecular weight tau in this system was found
      to be insoluble in 1% Triton-containing buffer, labeled proteins in 6-mm
      consecutive nerve segments were first separated into Triton-soluble and insoluble
      fractions. Two-dimensional gel electrophoresis and immunoblotting with anti-tau
      antibody confirmed the presence of tau among labeled, transported proteins in
      both fractions. Isoform composition of labeled tau was similar to that of bulk
      axonal tau, the most acidic species with apparent molecular mass of 66 kDa being
      the major component. Transport profiles obtained by measuring radioactivities
      associated with this major isoform showed that soluble and insoluble tau were
      transported at different rates. Insoluble tau, which contained the majority of
      tau-associated radioactivity, was transported at 1.7 mm/day in slow component a
      (SCa), whereas soluble tau was transported faster, at 3 mm/day, corresponding to
      the rate of slow component b (SCb). Cotransport of insoluble tau with insoluble
      tubulin in SCa suggests its association with stable microtubules.

PMID- 8858942
TI  - mu-calpain activation and calpain-mediated cytoskeletal proteolysis following
      traumatic brain injury.
AB  - Increasing evidence suggests that excessive activation of the calcium-activated
      neutral protease mu-calpain could play a major role in calcium-mediated neuronal
      degeneration after acute brain injuries. To further investigate the changes of
      the in vivo activity of mu-calpain after unilateral cortical impact injury in
      vivo, the ratio of the 76-kDa activated isoform of mu-calpain to its 80-kDa
      precursor was measured by western blotting. This mu-calpain activation ratio
      increased to threefold in the pellet of cortical samples ipsilateral to the
      injury site at 15 min, 1 h, 3 h, and 6 h after injury and returned to control
      levels at 24-48 h after injury. We also investigated the effect of mu-calpain
      activation on proteolysis of the neuronal cytoskeletal protein alpha-spectrin.
      Immunoreactivity for alpha-spectrin breakdown products was detectable within 15
      min after injury in cortical samples ipsilateral to the injury site. The levels
      of alpha-spectrin breakdown products increased in a biphasic manner, with a large
      increase between 15 min and 6 h after injury, followed by a smaller increase
      between 6 and 24 h after the insult. No further accumulation of alpha-spectrin
      breakdown products was observed between 24 and 48 h after injury.
      Histopathological examinations using hematoxylin and eosin staining demonstrated
      dark, shrunken neurons within 15 min after traumatic brain injury. No evidence of
      mu-calpain autolysis, calpain-mediated alpha-spectrin degradation, or hematoxylin
      and eosin neuronal pathology was detected in the contralateral cortex. Although
      mu-calpain autolysis and cytoskeletal proteolysis occurred concurrently with
      early morphological alterations, evidence of calpain-mediated proteolysis
      preceded the full expression of evolutionary histopathological changes. Our
      results indicate that rapid and persistent mu-calpain activation plays an
      important role in cortical neuronal degeneration after traumatic brain injury.
      Our data also suggest that specific inhibitors of calpain could be potential
      therapeutic agents for the treatment of traumatic brain injury in vivo.

PMID- 8858943
TI  - Severity of hyperammonemic encephalopathy correlates with brain ammonia level and
      saturation of glutamine synthetase in vivo.
AB  - Correlation among in vivo glutamine synthetase (GS) activity, brain ammonia and
      glutamine concentrations, and severity of encephalopathy was examined in
      hyperammonemic rats to obtain quantitative information on the capacity of GS to
      control these metabolites implicated in the etiology of hepatic encephalopathy.
      Awake rats were observed for neurobehavioral impairments after ammonium acetate
      infusion to attain a steady-state blood ammonia concentration of 0.9 (group A) or
      1.3 mumol/g (group B). As encephalopathy progressed from grade III to IV, brain
      ammonia concentration increased from 1.9 to 3.3 mumol/g and then decreased to 1.3
      mumol/g on recovery to grade III. In contrast, brain glutamine concentration was
      26, 23, and 21 mumol/g, respectively. NH(4+)-infused rats pretreated with L
      methionine DL-sulfoximine reached grade IV when brain ammonia and glutamine
      concentrations were 3.0 and 5.5 mumol/g, respectively; severity of encephalopathy
      correlates with brain ammonia, but not glutamine. In vivo GS activity, measured
      by NMR, was 6.8 +/- 0.7 mumol/h/g for group A and 6.2 +/- 0.6 mumol/h/g for group
      B. Hence, the in vivo activity, shown previously to increase with blood ammonia
      over a range of 0.4-0.64 mumol/g, approaches saturation at blood ammonia > 0.9
      mumol/g. This is likely to be the major cause of the observed accumulation of
      brain ammonia and the onset of grade IV encephalopathy.

PMID- 8858945
TI  - Differential expression of ciliary neurotrophic factor receptor in skeletal
      muscle of chick and rat after nerve injury.
AB  - The activities of ciliary neurotrophic factor (CNTF) were initially thought to be
      restricted to cells in the nervous system. However, the recent identification of
      its receptor specificity-conferring alpha component (CNTFR alpha) in skeletal
      muscle has provided the clue to the unexpected actions of CNTF in the periphery.
      In the present study, we demonstrated that the mRNA expression of CNTFR alpha in
      chick skeletal muscle was decreased by approximately 10-fold after nerve
      transection; this finding is in sharp contrast to the dramatic up-regulation
      observed in denervated rat muscle. As a first step toward investigating the
      differential regulation of CNTFR alpha in chick and rat, we examined the mRNA
      expression of CNTFR alpha in different types of muscle following nerve injury in
      young and adult animals. Our findings demonstrated that the differential
      expression of CNTFR alpha observed in denervated skeletal muscle of the chick and
      rat was not dependent on age or muscle type. The temporal profile of the changes
      in CNTFR alpha expression was, however, dependent on the age of the chick as well
      as the types of muscles. Furthermore, the low level of CNTFR alpha expression
      observed in denervated chick muscle recovered to almost control levels in
      regenerating skeletal muscle. Taken together, our findings provided the first
      extensive analysis on the mRNA expression of CNTFR alpha and the alpha subunit of
      the acetylcholine receptor in various skeletal muscles of the chick following
      nerve injury and regeneration.

PMID- 8858944
TI  - Amyloid beta-mediated oxidative and metabolic stress in rat cortical neurons: no
      direct evidence for a role for H2O2 generation.
AB  - H2O2 and free radical-mediated oxidative stresses have been implicated in
      mediating amyloid beta (1-40) [A beta (1-40)] neurotoxicity to cultured neurons.
      In this study, we confirm that addition of the H2O2-scavenging enzyme catalase
      protects neurons in culture against A beta-mediated toxicity; however, it does so
      by a mechanism that does not involve its ability to scavenge H2O2. A beta
      mediated elevation in intracellular H2O2 production is suppressed by addition of
      a potent H2O2 scavenger without any significant neuroprotection. Three
      intracellular biochemical markers of H2O2-mediated oxidative stress were
      unchanged by A beta treatment: (a) glyceraldehyde-3-phosphate dehydrogenase
      activity, (b) hexose monophosphate shunt activity, and (c) glucose oxidation via
      the tricarboxylic acid cycle. lonspray mass spectra of A beta in the incubation
      medium indicated that A beta itself is an unlikely source of reactive oxygen
      species. In this study we demonstrate that intracellular ATP concentration is
      compromised during the first 24-h exposure of neurons to A beta. Our results
      challenge a pivotal role for H2O2 generation in mediating A beta toxicity, and we
      suggest that impairment of energy homeostasis may be a more significant early
      factor in the neurodegenerative process.

PMID- 8858946
TI  - Susceptibility of hippocampal and cortical neurons to argon-mediated in vitro
      ischemia.
AB  - Neurons from cerebral cortex and hippocampal CA1 sector exhibit a striking
      difference in vulnerability to transient ischemia. To establish whether this
      difference is due to the inherent (pathoclitic) properties of these neurons, the
      ischemic susceptibility was studied in primary cortical and hippocampal cultures
      by using a new model of argon-induced in vitro ischemia. Neuronal cultures were
      exposed at 37 degrees C for 10-30 min to argon-equilibrated glucose-free medium.
      During argon equilibration, Po2 declined to < 2.5 torr within 1 min and
      stabilized shortly later at approximately 1.3 torr. After 30 min of in vitro
      ischemia, total adenylate was < 45% and ATP content < 15% of control in both
      types of culture. Cytosolic calcium activity increased from 15 to 50 nM.
      Reoxygenation of cultures after in vitro ischemia led to delayed neuronal death,
      the severity of which depended on the duration of in vitro ischemia but not on
      the type of neuronal cultures. Energy charge of adenylate transiently returned to
      approximately 90% of control after 3 h, but ATP content recovered only to 40% and
      protein synthesis to < 35%. Cytosolic calcium activity continued to rise after
      ischemia and reached values of approximately 500 nM after 3 h. The new argon
      induced in vitro ischemia model offers major advantages over previous methods,
      but despite this improvement it was not possible to replicate the differences in
      cortical and hippocampal vulnerability observed in vivo. Our study does not
      support the hypothesis that selective vulnerability is due to an inherent
      pathoclitic hypersensitivity.

PMID- 8858947
TI  - Molecular evolution of tau protein: implications for Alzheimer's disease.
AB  - The brains of patients with Alzheimer's disease contain deposits of
      hyperphosphorylated tau proteins that have polymerized into insoluble fibrils.
      These deposits, in neurofibrillary tangles and dystrophic neurites, correlate
      with loss of cells and synapses, and consequently with dementia. Neurofibrillary
      pathology occurs in humans, as well as certain ungulates, including goats, sheep,
      and cows, but not in nonhuman primates. We hypothesize that the differences among
      species in the propensity to develop neurofibrillary pathology may be
      attributable to variations in the amino acid sequence of tau proteins. To
      investigate this hypothesis, we sequenced tau-encoding mRNA transcripts from the
      brains of rhesus monkey and domesticated goat and compared them with the known
      sequences of tau mRNAs from humans. The major difference we observed was that
      some tau mRNAs from rhesus monkey neocortex contain exon 8, whereas this exon has
      not been found in cortical tau from human or goat. Cows express very low levels
      of exon 8, and they tend to develop sparse neurofibrillary pathology with aging.
      We also found a transcribed tau-related pseudogene in rhesus monkey, which may be
      present in humans. We propose that differences in the expression of tau and tau
      related protein sequences may underlie the predilection of human but not monkey
      brains to develop neurofibrillary degeneration.

PMID- 8858948
TI  - Chronic activation of the cyclic AMP signaling pathway promotes development and
      long-term survival of mesencephalic dopaminergic neurons.
AB  - Dibutyryl cyclic AMP (dbcAMP), a permeant analogue of cyclic AMP (cAMP),
      prevented, for at least 3 weeks, the death of tyrosine hydroxylase (TH)
      immunopositive dopaminergic neurons, which occurred spontaneously by apoptosis in
      mesencephalic cultures. Treatment with the cyclic nucleotide analogue also led to
      a significant increase in the uptake of [3H] dopamine, attesting that the rescued
      TH+ neurons were fully functional and differentiated. dbcAMP was most effective
      when added immediately after plating, but delayed treatment could still arrest
      the ongoing degenerative process. Trophic/survival effects were long-lasting,
      declining only progressively after withdrawal of dbcAMP from the culture medium.
      They were independent of cell density and still detectable in the absence of
      serum proteins. The effects of dbcAMP were mimicked by depolarizing
      concentrations of potassium and by agents that increase endogenous production of
      cAMP, such as forskolin or 3-isobutyl-1-methylxanthine, but not by native cAMP,
      which cannot cross cell membranes. Elimination of glial cells by arabinoside-C
      did not reduce the activity of dbcAMP. GABAergic neurons, also present in these
      cultures, were much less dependent on the cyclic nucleotide analogue for their
      survival, and serotoninergic cells were not dependent at all. Therefore, cAMP
      dependent signaling may be particularly crucial for the maturation and long-term
      survival of mesencephalic dopaminergic neurons.

PMID- 8858949
TI  - Delivery of human fibroblast growth factor-1 gene to brain by modified rat brain
      endothelial cells.
AB  - Fibroblast growth factor (FGF) is an endothelial cell mitogen and serves as a
      mitogen and/or differentiating factor that can be neuroprotective for other cell
      types within the CNS. We established brain microvascular endothelial cell lines
      that secrete FGF-1 with the ultimate goal of examining their usefulness as a
      cellular platform for FGF gene delivery to brain. A chimeric gene consisting of
      the secretory sequence of FGF-4 linked at the 5' end of human FGF-1 (sp
      hst/KS3:FGF-1) was transfected into rat microvascular endothelial cells
      previously altered to express the lacZ reporter gene (RBEZ), and numerous clones
      were found to secrete FGF-1 (RBEZ-FGF). Immunoblotting of conditioned medium
      demonstrated an 18-kDa protein corresponding to FGF-1. Conditioned medium from
      RBEZ-FGF cells enhanced [3H]thymidine incorporation in BALB/c3T3 fibroblasts by
      up to sevenfold when compared with conditioned medium of control cell lines,
      corresponding to as much as 110 ng of active FGF-1/mg of cell protein/24 h. RBEZ
      FGF cell lines remained contact-inhibited and proliferated independent of
      exogenous endothelial mitogens, in contrast to control lines that are mitogen
      dependent. Incubation of PC12 cells with RBEZ-FGF cells or their conditioned
      medium induced neurite outgrowth by PC12 cells. RBEZ-FGF cells survived following
      implantation to neonatal and adult rat caudate-putamen for at least 21 days based
      on 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside (X-gal) histochemistry,
      and FGF-1 gene expression by these cells in vivo was demonstrated by in situ
      hybridization and reverse transcriptase-PCR. These findings suggest that
      endothelial cells may be useful for FGF gene delivery to the CNS.

PMID- 8858950
TI  - Lazaroid treatment prevents death of cultured rat embryonic mesencephalic neurons
      following glutathione depletion.
AB  - Reactive oxygen species are believed to play a crucial role in situations where
      dopamine neurons die, such as in Parkinson's disease or during intracerebral
      transplantation of embryonic mesencephalic tissue. The present study was designed
      to address the question whether, and to what extent, the glutathione redox system
      is important for the viability of rat embryonic dopamine neurons in vitro.
      Furthermore, we studied whether the lazaroid U-83836E, a 2-methylaminochroman
      that inhibits lipid peroxidation, affects the survival of cultured mesencephalic
      neurons subjected to experimentally induced glutathione depletion. Glutathione
      depletion was achieved by exposing dissociated mesencephalic cell cultures to L
      buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, at four
      different concentrations (1, 10,100, and 1,000 microM). Dopamine neuron survival
      was significantly reduced by 65-94% in a concentration-dependent manner by 10
      1,000 microM BSO. The neurotoxic effects of BSO were almost completely prevented
      by supplementing the culture medium with 0.3 microM U-83836E. As assessed by HPLC
      analysis, BSO treatment was associated with a marked reduction of cellular
      glutathione content, and this depletion was not altered by the presence of U
      83836E. We conclude that in the present insult model of severe glutathione
      depletion, the lazaroid can afford efficient neuroprotection that does not seem
      to be mediated by a direct interaction with BSO or glutathione, but rather via an
      independent pathway.

PMID- 8858951
TI  - Calcium-dependent self-association of synaptotagmin I.
AB  - Synaptotagmin I, an integral membrane protein of secretory vesicles, appears to
      have an essential role in calcium-triggered hormone and neurotransmitter release.
      The large cytoplasmic domain of synaptotagmin I has two C2 domains that are
      thought to mediate calcium and phospholipid binding. A recombinant protein (p65 1
      5) comprised of the cytoplasmic domain was previously shown to aggregate purified
      chromaffin granules and artificial phospholipid vesicles in a calcium-dependent
      manner. p65 1-5 may be able to aggregate membrane vesicles by a self-association
      reaction. This hypothesis led us to investigate the ability of synaptotagmin I
      protein fragments to multimerize in vitro. We found that p65 1-5, in the absence
      of membranes, was able to self-associate to form large aggregates in a calcium
      dependent manner as shown by light-scattering assays and electron microscopy. In
      addition, a recombinant protein comprised of only the second half of the
      cytoplasmic domain, including the second C2 domain, was also able to self
      associate and aggregate phospholipid vesicles in a calcium-dependent manner. A
      recombinant protein comprised of only the first C2 domain was not able to self
      associate or aggregate vesicles. These results suggest that synaptotagmin I is
      able to bind calcium in the absence of membranes and that the second half of the
      cytoplasmic domain is able to bind calcium and mediate its multimerization in a
      calcium-dependent manner. The ability of synaptotagmin I protein fragments to
      multimerize in a calcium-dependent manner in vitro suggests that multimerization
      may have an important function in vivo.

PMID- 8858952
TI  - Novel neonicotinoid-agarose affinity column for Drosophila and Musca nicotinic
      acetylcholine receptors.
AB  - Neonicotinoids such as the insecticide imidacloprid (IMI) act as agonists at the
      insect nicotinic acetylcholine receptor (nAChR). Head membranes of Drosophila
      melanogaster and Musca domestica have a single high-affinity binding site for
      [3H]IMI with KD values of 1-2 nM and Bmax values of 560-850 fmol/mg of protein.
      Locusta and Periplaneta nAChRs isolated with an alpha-bungarotoxin (alpha-BGT)
      agarose affinity column are known to be alpha-subunit homooligomers. This study
      uses 1-[N-(6-chloro-3-pyridylmethyl)-N-ethyl]amino-1-amino-2-nitroethene++ +
      (which inhibits [3H]IMI binding to Drosophila and Musca head membranes at 2-3 nM)
      to develop a neonicotinoid-agarose affinity column. The procedure-introduction of
      Triton-solubilized Drosophila or Musca head membranes into this neonicotinoid
      based column, elution with IMI, and analysis by lithium dodecyl sulfate
      polyacrylamicle gel electrophoresis-gives only three proteins (69, 66, and 61
      kDa) tentatively assigned as putative subunits of the nAChR; the same three
      proteins are obtained with Musca using the alpha-BGT-agarose affinity column.
      Photoaffinity labeling of the Drosophila and Musca putative subunits from the
      neonicotinoid column with 125I-alpha-BGT-4-azidosalicylic acid gives a labeled
      derivative of 66-69 kDa. The yield is 2-5 micrograms of receptor protein from 1 g
      of Drosophila or Musca heads. Neonicotinoid affinity chromatography to isolate
      native Drosophila and Musca receptors will facilitate studies on the structure
      and function of insect nAChRs.

PMID- 8858953
TI  - Specific delay in the degradation of mitochondrial ATP synthase subunit c in late
      infantile neuronal ceroid lipofuscinosis is derived from cellular proteolytic
      dysfunction rather than structural alteration of subunit c.
AB  - Previously we indicated that a specific delay in subunit c degradation causes the
      accumulation of mitochondrial ATP synthase subunit c in lysosomes from the cells
      of patients with the late infantile form of neuronal ceroid lipofuscinosis (NCL).
      To explore the mechanism of lysosomal storage of subunit c in patient cells, we
      investigated the mechanism of the lysosomal accumulation of subunit c both in
      cultured normal fibroblasts and in in vitro cell-free incubation experiments.
      Addition of pepstatin to normal fibroblasts causes the marked lysosomal
      accumulation of subunit c and less accumulation of Mn(2+)-superoxide dismutase
      (SOD). In contrast, E-64-d stimulates greater lysosomal storage of Mn(2+)-SOD
      than of subunit c. Incubation of mitochondrial-lysosomal fractions from control
      and diseased cells at acidic pH leads to a much more rapid degradation of subunit
      c in control cells than in diseased cells, whereas other mitochondrial proteins,
      including Mn(2+)-SOD, beta subunit of ATP synthase, and subunit i.v. of
      cytochrome oxidase, are degraded at similar rates in both control and patient
      cells. The proteolysis of subunit c in normal cell extracts is inhibited markedly
      by pepstatin and weakly by E-64-c, as in the cultured cell experiments. However,
      there are no differences in the lysosomal protease levels, including the levels
      of the pepstatin-sensitive aspartic protease cathepsin D between control and
      patient cells. The stable subunit c in mitochondrial-lysosomal fractions from
      patient cells is degraded on incubation with mitochondrial-lysosomal fractions
      from control cells. Exchange experiments using radiolabeled substrates and
      nonlabeled proteolytic sources from control and patient cells showed that
      proteolytic dysfunction, rather than structural alterations such as the
      posttranslational modification of subunit c, is responsible for the specific
      delay in the degradation of subunit c in the late infantile form of NCL.

PMID- 8858954
TI  - Role of P-glycoprotein in the blood-brain transport of colchicine and
      vinblastine.
AB  - Classically, drug penetration through the blood-brain barrier depends on the
      lipid solubility of the substance, except for some highly lipophilic drugs, like
      colchicine and vinblastine, both substrates of P-glycoprotein, a drug efflux pump
      present at the luminal surface of the brain capillary endothelial cells.
      Colchicine and vinblastine uptake into the brain was studied in the rat using the
      in situ brain perfusion technique and two inhibitors of P-glycoprotein, verapamil
      and SDZ PSC-833. When rats were pretreated with PSC-833 (10 mg/kg, intravenous
      bolus), colchicine and vinblastine uptake was enhanced 8.42- and 9.08-fold,
      respectively, in all the gray areas of the rat brain studied. The mean colchicine
      distribution volume was increased from 0.67 +/- 0.41 to 5.64 +/- 0.70
      microliters/g and vinblastine distribution volume from 2.74 +/- 1.15 to 24.88 +/-
      4.03 microliters/g. When rats were pretreated with verapamil (1 mg/kg,
      intravenous bolus), colchicine distribution volume was increased 3.70-fold. The
      increase in colchicine and vinblastine did not differ between the eight brain
      gray areas. PSC-833 and verapamil pretreatment had no influence on the
      distribution volume of either drug in the choroid plexus. Nevertheless,
      distribution volumes remained small, considering the highly lipophilic nature of
      the substances. We suggest that P-glycoprotein is either only partially inhibited
      (difficulty of fully saturating P-glycoprotein, especially under in vivo
      conditions) or not the only barrier to these two drugs.

PMID- 8858955
TI  - Antagonistic effect of Na+ and Mg2+ on P2z purinoceptor-associated pores in
      dibutyryl cyclic AMP-differentiated NG108-15 cells.
AB  - The effect of replacement of extracellular Na+ with N-methyl-D-glucamine (NMG) on
      P2 receptor signaling pathways was investigated in dibutyryl cyclic AMP
      differentiated NG108-15, cells. Benzoylbenzoic ATP (BzATP) dose-dependently
      increased the cytosolic Ca2+ concentration ([Ca2+]i) with an EC50 value of 230
      microM. Replacement of Na+ with NMG as well as removal of Mg2+ from the bathing
      buffer potentiated ethidium bromide uptake, [Ca2+]i increase, and 45Ca2+ uptake
      in response to ATP or BzATP. In contrast, in the presence of 5 mM Mg2+ to limit
      the amount of ATP4-, replacement of Na+ with NMG had no effect on the ATP-induced
      [Ca2+]i increase but caused a markedly larger [Ca2+]i increase when the
      calculated concentration of ATP4- was > 10 microM. The calculated EC50 value for
      ATP4- stimulation of the [Ca2+]i increase was 23 microM in NG108-15 cells. In
      vascular smooth muscle cells, intracellular Ca2+ release was the major pathway
      for the ATP-induced [Ca2+]i increase; both removal of Mg2+ and replacement of Na+
      with NMG did not affect the action of ATP. These data suggest that ATP(4-)
      promoted pores are antagonized by Na+ and Mg2+ in dibutyryl cyclic AMP
      differentiated NG108-15 cells.

PMID- 8858956
TI  - Identification of two molecular species of rat brain phosphatidylcholine that
      rapidly incorporate and turn over arachidonic acid in vivo.
AB  - In vivo rates of arachidonic acid incorporation and turnover were determined for
      molecular species of rat brain phosphatidylcholine (PtdCho) and
      phosphatidylinositol (PtdIns). [3H]Arachidonic acid was infused intravenously in
      pentobarbital-anesthetized rats at a programmed rate to maintain constant plasma
      specific activity for 2-10 min. At the end of infusion, animals were killed by
      microwave irradiation, and brain phospholipids were isolated, converted to
      diacylglycerobenzoates, and resolved as molecular species by reversed-phase HPLC.
      Most [3H] arachidonate (> 87%) was incorporated into PtdCho and PtdIns, with
      arachidonic acid at the sn-2 position and with oleic acid (18:1), palmitic acid
      (16:0), or stearic acid (18:0) at the sn-1 position. However, 10-15% of labeled
      brain PtdCho eluted in a small peak containing two molecular species with
      arachidonic acid at the sn-2 position and palmitoleic acid (16:1) or linoleic
      acid (18:2) at the sn-1 position. Analysis demonstrated that tracer was present
      in both the 16:1-20:4 and 18:2-20:4 PtdCho species at specific activities 10-40
      times that of the other phospholipids. Based on the measured mass of arachidonate
      in each phospholipid molecular species, half-lives were calculated for
      arachidonate of < 10 min in 16:1-20:4 and 18:2-20:4 PtdCho and 1-3 h in 16:0
      20:4, 18:1-20:4 PtdCho and PtdIns. The very short half-lives for arachidonate in
      the 16:1-20:4 and 18:2-20:4 PtdCho molecular species suggest important roles for
      these molecules in brain phospholipid metabolism and signal transduction.

PMID- 8858957
TI  - Portacaval anastomosis results in altered neuron--astrocytic metabolic
      trafficking of amino acids: evidence from 13C-NMR studies.
AB  - 13C-NMR spectroscopy was used to evaluate the dynamic consequences of portacaval
      anastomosis on neuronal and astrocytic metabolism and metabolic trafficking
      between neurons and astrocytes. Glutamate is predominantly labeled from [1
      13C]glucose, whereas [2-13C]acetate is more efficient in labeling glutamine, in
      accordance with its primary metabolism in astrocytes. Alanine and succinate
      labeling was only observed with [1-13C]glucose as precursor. Brain [1-13C]glucose
      metabolism in portacaval-shunted rats was similar to that in sham-operated
      controls with the exception of labeled glutamine and succinate formation, which
      was increased in shunted rats. The 13C enrichment was, however, decreased owing
      to an increase in total glutamine and succinate. Using [2-13C]acetate, on the
      other hand, flux of astrocytic label to neurons was severely decreased because
      label incorporation into glutamate, aspartate, and GABA was decreased following
      portacaval shunting. The latter amino acids are predominantly localized in
      neurons. These findings demonstrate that metabolic trafficking of amino acids
      from astrocytes to neurons is impaired in portacaval-shunted rats.

PMID- 8858958
TI  - Metabolic precursors and compartmentation of cerebral GABA in vigabatrin-treated
      rats.
AB  - The metabolic precursors and cerebral compartmentation of the augmented GABA pool
      induced by vigabatrin, an irreversible inhibitor of GABA transaminase, have been
      investigated by 13C NMR. Adult rats receiving rat chow ad libitum were given
      either drinking water only or drinking water containing 2.5 g/L vigabatrin for 7
      days. Both groups of animals were infused either with [1,2(-13)C2]acetate (15
      mumol/min/100 g body weight), an exclusive precursor of GABA formation through
      the glial glutamine pathway, or with [1,2(-13)C2]glucose (15 mumol/min/100 g body
      weight), a substrate that can produce GABA through the glial glutamine pathway or
      by direct metabolism in the neurons. The brains were frozen in situ, extracted
      with perchloric acid, and analyzed by 13C NMR. In vigabatrin-treated animals
      [13C]glutamine, a common intermediate for [13C]GABA synthesis from glucose or
      acetate, was accumulated to similar amounts during infusions with [1,2(
      13)C2]glucose or [1,2(-13)C2]acetate. However, [13C]GABA accumulation was
      sevenfold higher during [1,2(-13)C2]glucose infusions or twofold higher during
      [1,2(-13)C2]acetate infusions. These results show that the direct pathway of GABA
      formation by neuronal metabolism of glucose predominates over the alternative
      pathway through glial glutamine. Near-equilibrium relationships of the
      aminotransferases of GABA and aspartate imply that the observed [13C]GABA
      accumulation occurs initially in the neuronal compartment.

PMID- 8858959
TI  - Partitioning of CO2 production between glucose and lactate in excised sympathetic
      ganglia, with implications for brain.
AB  - Chains of lumbar sympathetic ganglia from 15-day-old chicken embryos were
      incubated for 4 h at 36 degrees C in a bicarbonate-buffered salt solution
      equilibrated with 5% CO2-95% O2. Glucose (1-10 mM), lactate (1-10 mM), [U
      14C]glucose, [1(-14)C]glucose, [6(-14)C]glucose, and [U-14C]lactate were added as
      needed. 14CO2 output was measured continuously by counting the radioactivity in
      gas that had passed through the incubation chamber. Lactate reduced the output of
      CO2 from [U(-14)C]glucose, and glucose reduced that from [U(-14)C]lactate. When
      using uniformly labeled substrates in the presence of 5.5 mM glucose, the output
      of CO2 from lactate exceeded that from glucose when the lactate concentration was
      > 2 mM. The combined outputs at each concentration tested were greater than those
      from either substrate alone. The 14CO2 output from [1(-14)C]glucose always
      exceeded that from [6(-14)C]glucose, indicating activity of the hexose
      monophosphate shunt. Lactate reduced both of these outputs, with the maximum
      difference between them during incubation remaining constant as the lactate
      concentration was increased, suggesting that lactate may not affect the shunt.
      Modeling revealed many details of lactate metabolism as a function of its
      concentration. Addition of a blood-brain barrier to the model suggested that
      lactate can be a significant metabolite for brain during hyperlactemia,
      especially at the high levels reached physiologically during exercise.

PMID- 8858960
TI  - Depletion of neuronal endoplasmic reticulum calcium stores by thapsigargin:
      effect on protein synthesis.
AB  - We have used thapsigargin (TG), a specific, irreversible inhibitor of endoplasmic
      reticulum (ER) Ca(2+)-ATPases, and caffeine, an agonist of the ryanodine
      receptor, to study the effect of emptying of ER calcium stores on protein
      synthesis in neuronal cells. TG at 1 microM caused a permanent inhibition of
      protein synthesis in hippocampal slices from 3-week-old rats but no inhibition in
      slices prepared from 2-month-old animals. Caffeine at 10 mM caused a reduction of
      protein synthesis in both 3-week- and 2-month-old rats immediately after
      exposure, but complete recovery of protein synthesis occurred within 30 min after
      treatment. In neuronal cells, TG produced an almost complete inhibition of
      protein synthesis that was only partially reversed over a 24-h recovery period.
      TG did not significantly affect neuronal ATP levels or energy charge. Fifty
      percent inhibition of protein synthesis was achieved with approximately 5 nM TG.
      Recovery of protein synthesis after TG treatment was significantly hindered when
      serum was omitted from the medium after TG exposure, suggesting that serum
      promotes recovery of ER calcium homeostasis. It is concluded that TG is a
      suitable tool for the study of the mechanisms of protein synthesis inhibition
      after transient cerebral ischemia. The possibility that disturbances in ER
      calcium homeostasis may contribute to the pathological process of ischemic cell
      death is discussed.

PMID- 8858961
TI  - Accelerated myelinogenesis by dietary lipids in rat brain.
AB  - Our previous work showed an early development of behavioral reflexes in rats
      whose mothers had been fed, during pregnancy and lactation, a lipid fraction
      extracted from yeast grown on n-alkanes (which contain 50% odd-chain fatty acids)
      in comparison with controls fed a margarine diet. To clarify whether the observed
      changes might be linked to an early myelination, we have investigated mRNAs
      involved in myelin synthesis in the brains of offspring at 5 days of age by
      northern blot and in situ hybridization. Northern blot analysis showed that
      proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) mRNAs
      were higher in animals on the lipid diet compared with controls. In situ
      hybridization with probes specific for PLP, myelin basic protein, and MOG mRNA
      showed significantly higher numbers of positive cells in test animals compared
      with controls in all brain regions. This study shows an acceleration of
      myelinogenesis induced by dietary lipids. These data can give a new insight in
      the therapeutical approaches involved to promote repair in demyelinating
      diseases.

PMID- 8858962
TI  - Involvement of leukemia inhibitory factor in the increases in galanin and
      vasoactive intestinal peptide mRNA and the decreases in neuropeptide Y and
      tyrosine hydroxylase mRNA in sympathetic neurons after axotomy.
AB  - In response to axonal injury, noradrenergic sympathetic neurons of the adult
      superior cervical ganglion (SCG) alter their neurotransmitter phenotype. These
      alterations include increases in the levels of the neuropeptides, galanin,
      vasoactive intestinal peptide (VIP), and substance P (SP) and a decrease in the
      catecholamine biosynthetic enzyme tyrosine hydroxylase (TH). Previous studies
      have indicated that after axotomy in vivo, leukemia inhibitory factor (LIF) plays
      an important role in increasing the contents of galanin and VIP in the SCG. In
      the present study, by examining the time courses of the changes in LIF and
      neuropeptide mRNA and by using LIF null mutant mice, we have determined that LIF
      alters neuropeptide content in part by increasing levels of peptide mRNA. In
      addition, LIF also makes a small contribution to the axotomy-induced down
      regulation of mRNA encoding TH and neuropeptide Y, both of which are normally
      expressed at high levels in the SCG. Finally, by using a LIF-blocking antiserum,
      this cytokine was found to regulate SP expression in an in vitro axonal injury
      model. Thus, after axotomy, a single factor, LIF, participates in the down
      regulation of peptides/proteins involved in normal neurotransmission and the up
      regulation of a group of neuropeptides normally not present in the SCG that may
      be involved in regeneration.

PMID- 8858963
TI  - Agmatinase activity in rat brain: a metabolic pathway for the degradation of
      agmatine.
AB  - Agmatinase, the enzyme that hydrolyzes agmatine to form putrescine and urea in
      lower organisms, was found in rat brain. Agmatinase activity was maximal at pH 8
      8.5 and had an apparent K(m) of 5.3 +/- 0.99 mM and a Vmax of 530 +/- 116 nmol/mg
      of protein/h. After subcellular fractionation, most of the enzyme activity was
      localized in the mitochondrial matrix (333 +/- 5 nmol/mg of protein/h), where it
      was enriched compared with the whole-brain homogenate (7.6-11.8 nmol/mg of
      protein/ h). Within the CNS, the highest activity was found in hypothalamus, a
      region rich in imidazoline receptors, and the lowest in striatum and cortex. It
      is interesting that other agmatine-related molecules such as arginine
      decarboxylase, which synthesizes agmatine, and I2 imidazoline receptors, for
      which agmatine is an endogenous ligand, are also located in mitochondria. The
      results show the existence of rat brain agmatinase, mainly located in
      mitochondria, indicating possible degradation of agmatine by hydrolysis at its
      sites of action.

PMID- 8858964
TI  - Nitric oxide synthase type II mRNA stability is translation- and transcription
      dependent.
AB  - Nitric oxide synthase (NOS) type II is induced in many cell types in response to
      cytokines or endotoxin. The duration of type II NOS mRNA expression in astroglial
      cells and macrophages in vitro is brief, even in the continuous presence of
      inducers, and their removal dramatically accelerates mRNA decay. Addition of
      cycloheximide, in the presence or absence of actinomycin D, protected the mRNA
      from degradation. Whereas type II NOS mRNA was partially stabilized by
      actinomycin D, manganese superoxide dismutase mRNA was almost completely
      stabilized. This suggests that type II NOS mRNA stability is regulated via
      transcription- as well as translation-dependent processes and that the effect of
      actinomycin D is mRNA specific.

PMID- 8858966
TI  - Attenuation of beta-amyloid neurotoxicity in vitro by potassium-induced
      depolarization.
AB  - The cell death of cultured neurons triggered by beta-amyloid peptides has been
      theorized to model, at least in part, the neurodegeneration associated with
      Alzheimer's disease. To investigate potential strategies to interrupt beta
      amyloid neurotoxicity in vitro, we examined the effects of potassium-induced
      membrane depolarization, a treatment previously demonstrated to reduce
      development-related apoptosis in cultured neurons. We report here that cultured
      rat hippocampal neurons pretreated for several hours with 30 mM KCl exhibit
      significantly reduced vulnerability to aggregated beta-amyloid peptides. The
      potassium-mediated neuroprotection was mimicked by activation of voltage
      sensitive calcium channels using S(-)-Bay K8644 and was attenuated by R(+)-Bay K
      8644, a blocker of voltage-dependent calcium channels, and KN-82, an inhibitor of
      calcium/calmodulin-dependent protein kinase II. The protein synthesis inhibitor
      cycloheximide also attenuated beta-amyloid neurotoxicity. Addition of
      cycloheximide following 30 mM KCl significantly increased protection offered by
      membrane depolarization, whereas cycloheximide addition during membrane
      depolarization blocked the protective effect. These data suggest that one
      cellular pathway that can inhibit neuronal death induced by beta-amyloid involves
      calcium influx through voltage-sensitive channels followed by stimulation of
      calcium/calmodulin-dependent protein kinase activity and synthesis of new
      protein(s).

PMID- 8858965
TI  - The neuronal nitric oxide synthase inhibitor, 7-nitroindazole, protects against
      methamphetamine-induced neurotoxicity in vivo.
AB  - The present study was undertaken to investigate whether the relatively selective
      neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects
      against methamphetamine (METH)-induced neurotoxicity. Male Swiss Webster mice
      received the following treatments (i.p.; q 3 h x 3): (a) vehicle/saline, (b) 7-NI
      (25 mg/kg)/saline, (c) vehicle/METH (5 mg/kg), and (d) 7-NI (25 mg/kg)/METH (5
      mg/kg). On the second day, groups (a) and (b) received two vehicle injections,
      and groups (c) and (d) received two 7-NI injections (25 mg/kg, each).
      Administration of vehicle/METH resulted in 68, 44, and 55% decreases in the
      concentration of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid,
      respectively, and a 48% decrease in the number of [3H]mazindol binding sites in
      the striatum compared with control values. Treatment with 7-NI (group d) provided
      full protection against the depletion of dopamine and its metabolites and the
      loss of dopamine transporter binding sites. Administration of 7-NI/saline (group
      b) affected neither the tissue concentration of dopamine and its metabolites nor
      the binding parameters of [3H] mazindol compared with control values. 7-NI had no
      significant effect on animals' body temperature, and it did not affect METH
      induced hyperthermia. These findings indicate a role for nitric oxide in
      methamphetamine-induced neurotoxicity and also suggest that blockade of NOS may
      be beneficial for the management of Parkinson's disease.

PMID- 8858967
TI  - Effects of gonadal steroids on vascular function.
AB  - Estrogen and other sex steroid hormones can affect multiple functions of the
      vascular wall including production and activity of endothelium-derived factors,
      expression of adhesion molecules, contraction of the smooth muscle to adrenergic
      nerve stimulation and smooth muscle proliferation and migration. Effects on
      response of the smooth muscle may be associated with regulation of surface
      receptors, second messenger systems and contractile protein isoforms. Sex steroid
      hormones may act synergistically with other hormones to modulate vascular
      reactivity across the normal ovarian cycle and during pregnancy. Estrogen may
      also affect remodeling of the vascular wall through inhibition of smooth muscle
      cell proliferation, stimulation of cell migration and secretion of matrix
      proteins. It is becoming apparent that modulation of vascular function by sex
      steroid hormones involves complex interactions. Not all actions of estrogen can
      be explained by genomic regulation of protein synthesis. Continued progress in
      understanding how hormones modulate vascular function will depend, in part, on
      clearer interpretation of data relative to the particular conditions of each
      experiment. Important aspects to be considered include the effect of gender and
      vessel type on the distribution and function of hormone receptors present in the
      vessel wall; use of hormones within physiological concentration ranges; and more
      precise determination of the influence of hormone treatment duration whether
      acute, subacute or chronic.

PMID- 8858968
TI  - In vivo and in vitro characterization of CYP2E1 activity in Japanese and
      Caucasians.
AB  - Chlorzoxazone's disposition after oral administration was determined in 20 young
      healthy Caucasian men and a similar group of Japanese men. The drug's plasma
      concentrations were significantly higher and its rate of elimination slower in
      Japanese compared to Caucasian men. Accordingly, chlorzoxazone's oral clearance
      was smaller (40%) in Japanese men and a similar difference (30%) was still
      apparent after normalizing for body weight (3.74 +/- 1.23 versus 5.05 +/- 1.41
      ml.min-1.kg-1, P < .05). This slower elimination was associated with a reduced
      (fractional) clearance by 6-hydroxylation (2.34 +/- 1.04 ml.min-1.kg-1 versus
      3.23 +/- 1.10, P < .05). Because such metabolism is mediated by cytochrome
      P4502E1 (CYP2E1), these findings suggest a lower level of the enzyme's catalytic
      activity in Japanese men. This was confirmed by in vitro studies with microsomes
      prepared from livers of individuals representative of the two racial groups.
      CYP2E1 levels were lower (61% P < .002) and CYP2E1-mediated chlorzoxazone 6
      hydroxylase (22%, P < .001) and aniline 4-hydroylase (35%, P < .0001) activities
      were reduced in Japanese preparations compared to those from Caucasians. No
      relationships were found between measures of CYP2E1 activity, both in vivo and in
      vitro, and genomic polymorphisms in the CYP2E1 gene identified by Rsal/Pstl and
      Dral restriction fragment length polymorphisms. Collectively, these data show an
      interracial difference in CYP2E1 activity. Because this enzyme is importantly
      involved in the activation of environmental procarcinogens, such a difference may
      account, in part, for the lower rate of some cancers, e.g., lung cancer, in
      Japanese compared to Caucasians men.

PMID- 8858969
TI  - Evaluation of sex- and strain-dependency of cocaine-induced immunosuppression in
      B6C3F1 and DBA/2 mice.
AB  - The objective of these studies was to determine if the immunotoxic effects of
      cocaine in mice are sex- and strain-dependent, a profile of activity previously
      described for cocaine-induced hepatotoxicity. The latter effect has been
      attributed to differences in the metabolism of cocaine by the cytochrome P-450
      system. Subchronic, (14-day) in vivo administration of cocaine to female B6C3F1
      mice showed a significant decrease (80%) in the T-dependent primary antibody
      response only at 80 mg/kg, although exposure to 60 mg/kg produced only a 20%
      decrease. In contrast, exposure to 60 mg/kg cocaine in female DBA/2 mice produced
      a significant decrease of 50%. An even greater effect was observed in male mice
      where exposure to 40 mg/kg cocaine produced > 50% decreases in both B6C3F1 and
      DBA/2 mice. Similar results were obtained when male mice were only exposed for 7
      days. Confirmation that hepatotoxicity occurred with a similar profile of sex-
      and strain-dependency was obtained in parallel studies when serum chemistries
      were measured. The immunosuppressive activity of cocaine in female B6C3F1 mice
      was markedly increased when mice were pretreated with phenobarbital, a cytochrome
      P-450 inducer. These results extend our previous studies that indicated that
      cocaine-induced immunosuppression occurs under conditions that are consistent
      with a mechanism mediated through metabolism by the cytochrome P-450 pathway.

PMID- 8858970
TI  - Melatonin modulation of presynaptic nicotinic acetylcholine receptors in the rat
      vas deferens.
AB  - Melatonin, the pineal hormone produced during the dark phase of the light-dark
      cycle, modulates neuronal acetylcholine receptors located presynaptically on the
      sympathetic nerve terminals of the rat vas deferens. The pD2 values for nicotine
      were significantly higher at night (4.20 +/- 0.01) than in the afternoon (3.80 +/
      0.07). Exogenous melatonin shifted the concentration-response curves for
      nicotine to the left, mimicking the effect of darkness. Melatonin modifies both
      the displacement and the saturation curves of [3H](-)nicotine binding. In
      membranes from animals killed at 15:00 h, the binding of [3H](-)nicotine (5-6 nM)
      was first potentiated and then inhibited by sequential concentrations of (
      )nicotine. Higher concentrations of [3H](-)nicotine (50-60 nM) were displaced by
      all concentrations of nonlabeled ligand. However, when membranes from tissues
      exposed to melatonin (exogenous or endogenous) were tested, the lower [3H](
      )nicotine concentration was displaced progressively by increasing concentrations
      of nonlabeled ligand. Equilibrium binding studies show a single class of high
      affinity nicotinic binding sites with an apparent Kd value of 16 nM and an
      average maximal number of binding sites of 66 fmol mg-1 protein when animals were
      killed at the afternoon. Melatonin, although it did not change the properties of
      high-affinity binding sites, induced the appearance of a second population of
      lower apparent affinity (Kd = 36.7 nM; Bmax = 185.4 fmol/mg). Melatonin does not
      modify the functional response and the displacement of [3H](-)nicotine by
      dimethylphenylpiperazinium. The data suggest that nicotinic neuronal
      acetylcholine receptors stimulated by dimethylphenylpiperazinium do not change
      between the light and dark phases. Rather, the higher sensitivity to nicotine in
      prostatic portions incubated with exogenous melatonin, and in organs from animals
      killed at night, after the rise of endogenous melatonin, is probably due to the
      appearance of low-affinity neuronal nicotinic ACh binding sites.

PMID- 8858971
TI  - Mechanism of clocinnamox blockade of opioid receptors: evidence from in vitro and
      ex vivo binding and behavioral assays.
AB  - In behavioral experiments, the cinnamoylaminomorphinone clocinnamox (CCAM) has
      been shown to act as an insurmountable antagonist of mu, but not delta or kappa
      opioid agonists. In contrast, CCAM displayed only moderate mu selectivity (29:6:1
      for mu:delta:kappa) in radioligand displacement experiments using mouse brain
      membranes. In the present study, the apparent discrepancy between the high mu
      selectivity of the insurmountable functional antagonism of CCAM and its only
      moderate mu selectivity in in vitro binding experiments was resolved by in vitro
      washout experiments and ex vivo binding experiments involving all three opioid
      receptor types. In the ex vitro washout experiments, CCAM-mediated mu receptor
      binding inhibition could not be reversed even after allowing for 8 hr hr
      dissociation, whereas the CCAM inhibition of delta and kappa receptor binding was
      time-dependently reversed. In the ex vivo binding experiments, 1 hr pretreatment
      of mice with 10 mg/kg of CCAM i.p. decreased ex vivo [D-Ala2, N-Me-Phe4, Gly5-ol]
      enkephalin ([3H]DAMGO) binding (tested at > or = 5 * Kd) by 90%, paralleled by an
      88% decrease in mu receptor density in equilibrium saturation binding assays. Ex
      vivo [3H]DAMGO binding returned to control levels with a T1/2 of 2.7 to 4.2 days
      (independent of the CCAM dose), the effect being predominantly due to a recovery
      of mu receptor density. The CCAM inhibition of ex vivo [3H]DAMGO binding was dose
      dependent and could be prevented in part by simultaneous administration of the
      protein synthesis inhibitor cylcoheximide. In contrast to the ex vivo binding of
      [3H]DAMGO, ex vivo binding of p-[3H]CI-[D-Pen2, D-Pen5]enkephalin or (-)
      [3H]bremazocine (in the presence of 1 microM DAMGO and 1 microM [D-Pen6, D
      Pen5]enkephalin) was not affected by CCAM pretreatment. Finally, ex vivo
      [3H]DAMGO binding inhibition data correlated well with mu receptor population
      changes estimated by Black and Leff analysis of behavioral (antinociception)
      experiments (T1/2 of receptor reappearance, 3.2 days). Thus, although CCAM
      reversibly interacted with mu, delta and kappa opioid receptors, only binding to
      mu receptors was wash-resistant. Binding of methoclocinnamox, a codeinone CCAM
      precursor with mu agonistic activity, seemed to be at least partially reversible,
      even at mu receptors.

PMID- 8858972
TI  - Dilazep and its derivative, K-7259, attenuate mechanical derangement induced by
      palmitoyl-L-carnitine in the isolated, perfused rat heart.
AB  - The effect of dilazep, a potentiator of the adenosine-mediated effects, on the
      palmitoyl-L-carnitine (PALCAR)-induced mechanical derangement was studied in the
      isolated rat heart and compared with that of K-7259, a dilazep derivative having
      less potentiating action on the adenosine-mediated effects. The heart was
      perfused aerobically by the Langendorff's technique at a constant flow and driven
      electrically. PALCAR (5 microM) decreased the left ventricular developed pressure
      and increased the left ventricular end diastolic pressure in the heart (i.e.,
      mechanical dysfunction). These mechanical alterations induced by PALCAR were
      attenuated by dilazep (1 microM) and K-7259 (1 microM). In contrast, adenosine
      (10 or 100 microM) did not attenuate the PALCAR-induced mechanical derangement.
      On the other hand, neither dilazep nor K-7259 modified the mechanical function of
      the normal (PALCAR-untreated) heart. These results suggest that dilazep and K
      7259 attenuate the PALCAR-induced mechanical derangement and that the protective
      action of both drugs is not due to potentiation of adenosine-mediated effects.

PMID- 8858973
TI  - Pretreatment with pertussis toxin differentially modulates morphine- and beta
      endorphin-induced antinociception in the mouse.
AB  - The experiments were designed to determine the role of pertussis toxin-(PTX)
      sensitive G-proteins Gi/Go in the brain and spinal cord in antinociception
      induced by epsilon-opioid receptor agonist beta-endorphin (beta-EP) and mu-opioid
      receptor agonist morphine. The effects of intracerebroventricular (i.c.v.) or
      intrathecal (i.t.) pretreatment with PTX on antinociception induced by morphine,
      beta-endorphin (beta-EP) and other selective opioid receptor agonists given
      i.c.v. or i.t. were studied in male ICR mice. Antinociception was assessed by the
      tail-flick and hot-plate tests. An i.c.v. pretreatment with PTX (0.5 microgram)
      caused a time- and dose-dependent attenuation of the tail-flick and hot-plate
      inhibition induced by i.c.v.-challenged morphine-induced antinociception.
      However, the same pretreatment with PTX did not affect the antinociception
      induced by i.c.v.-administered beta-EP. The tail-flick and hot-plate inhibition
      induced by selective mu-, delta- and kappa-opioid receptor agonist, DAMGO, [D
      Ala2]deltorphin II and U50,488H, respectively, given i.c.v. was also attenuated
      by the i.c.v. pretreatment with PTX. An i.t. pretreatment with PTX (0.5
      microgram) blocked markedly the tail-flick inhibition induced by morphine and
      beta-EP given i.c.v. However, the same treatment did not affect the hot-plate
      inhibition induced by beta-EP and attenuated, to a lesser degree, the hot-plate
      inhibition induced by morphine given i.c.v. An i.t. pretreatment with PTX blocked
      the tail-flick inhibition induced by selective delta 2-, alpha 2 and 5-HT
      receptor agonist [D-Ala2]deltorphin, norepinephrine and 5-HT, respectively, given
      i.t. Our results indicate that the antinociception induced by mu-, delta-, kappa
      opioid receptor agonists given supraspinally is mediated by respectively opioid
      receptors that are coupled to PTX-sensitive Gi/Go proteins at the supraspinal
      sites and subsequently mediated by the activation of PTX-sensitive Gi/Go coupled
      receptors in the spinal cord. However, the antinociception induced by beta-EP
      given supraspinally is mediated by the PTX-resistant epsilon-opioid receptors at
      the supraspinal sites and subsequently activation of the delta 2-opioid receptors
      in the spinal cord that is sensitive to the pretreatment with PTX.

PMID- 8858974
TI  - Restoration of ischemic contractile failure of indo-1-loaded guinea pig heart by
      a calcium sensitizer, MCI-154.
AB  - We investigated the effect of a new Ca++ sensitizer, MCI-154, which is known to
      increase myofibrillar Ca++ sensitivity and maximal Ca(++)-activated force, on
      Ca++ transients and left ventricular (LV) function in indo-1-loaded Langendorff
      guinea plg hearts subjected to a reduction in coronary perfusion pressure from 80
      to 40 mm Hg. During low-flow ischemia, LV contractility decreased by 50%, whereas
      systolic and diastolic indo-1 fluorescence ratios increased by 10%. The treatment
      with MCI-154 (10(-10) to 10(-6) M) 15 min after ischemia effectively restored the
      depressed LV function with little effect on indo-1 ratio. EMD 53998 (10(-9) to
      10(-6) M), which also acts on maximal Ca(++)-activated force, restored LV
      function with a minimal impact on indo-1 ratio, but at 10(-5) M, EMD 53998 caused
      diastolic dysfunction, and its beneficial effect on systolic function
      disappeared. The relation between indo-1 ratio and LV contractility showed that
      MCI-154 and EMD 53998 restored ischemic contractile failure by Ca(++)-sensitizing
      action. It was noted that the restoration of LV dysfunction by MCI-154 or EMD
      53998 was more pronounced than that by pimobendan, which acts primarily on Ca++
      sensitivity. In contrast, the phosphodiesterase inhibitor milrinone restored LV
      function, but it doubled the increase in indo-1 ratio during ischemia. These
      findings suggest that a decrease in myofilament Ca++ responsiveness may be an
      important cause of ischemic contractile failure and that the restoration of
      depressed Ca++ responsiveness by intervention such as MCI-154 may be a promising
      approach for restoring the depressed function.

PMID- 8858975
TI  - Binding of the volatile anesthetic halothane to the hydrophobic core of a tetra
      alpha-helix-bundle protein.
AB  - Although volatile general anesthetics interact with several proteins, little is
      known about the location or characteristics of the binding sites at the molecular
      level. A detailed structural description of how anesthetics associate with
      macromolecules is necessary for understanding anesthetic mechanisms of action.
      The recent introduction of designed synthetic proteins provides new opportunities
      for obtaining structural and functional information on anesthetic-protein
      interactions. A synthetic tetra-alpha-helix-bundle protein was used to examine
      the interaction of halothane with a designed protein interior. The tetra-alpha
      helix-bundle comprises 124 residues in the form of two identical 62-residue di
      alpha-helical peptides, held together in an all-parallel bundle by hydrophobic
      forces. Steady-state and time-resolved tryptophan fluorescence and circular
      dichroism spectroscopy were used to study the anesthetic-protein interaction.
      Halothane quenches bundle tryptophan fluorescence with a dissociation constant of
      2.3 +/- 0.4 mM and a Hill number of 0.9 +/- 0.1. Tryptophan fluorescence decay
      analysis indicates that halothane quenches the protein fluorescence by a static
      mechanism. Circular dichroism spectroscopy revealed no change in protein
      secondary structure on exposure to halothane. Dissociation of the tetra-alpha
      helix-bundle into 62-residue di-alpha-helical peptides by trifluoroethanol
      eliminated the halothane-protein interaction. The results suggest that halothane
      binds to the hydrophobic interior of the tetra-alpha-helix-bundle, close to the
      tryptophan residues. The protein tertiary and quaternary structures are required
      for anesthetic binding. This study demonstrates the feasibility of using
      synthetic tetra-alpha-helix-bundles as model anesthetic-binding proteins. The use
      of de novo designed bundle proteins should allow structural, energetic and
      functional descriptions of anesthetic-protein interactions.

PMID- 8858976
TI  - [3H]MDL 105,519, a high-affinity radioligand for the N-methyl-D-aspartate
      receptor-associated glycine recognition site.
AB  - MDL 105,519 [(E)-3-(2-phenyl-2-carboxyethenyl)-4, 6-dichloro-1H-indole-2
      carboxylic acid] is a potent ligand at the N-methyl-D-aspartate (NMDA) receptor
      associated glycine recognition site and is a noncompetitive inhibitor of NMDA
      receptor-mediated responses in vitro and in vivo. For purposes of characterizing
      its action at the glycine binding site, a halogenated analog was reduced with
      tritium to form radiolabeled MDL 105,519. [3H]MDL 105,519 bound to rat brain
      membranes with high affinity (Kd = 3.77 nM) and capacity (Bmax = 12.1 pmol/mg
      protein). Isolation of bound ligand by filtration gave identical levels of
      specific binding as did centrifugation techniques. The kinetics of the binding
      reaction were studied. Association was monophasic with Kon equal to 7.0 x 10(7) M
      1.min-1. Dissociation was also monophasic with the Koff value calculated from
      association experiments (0.257 min-1) being similar to that measured directly in
      dissociation experiments (0.232 min-1). A kinetically derived value for the
      equilibrium dissociation constant was calculated with the two values for Koff and
      the association rate constant. The respective values (Kd = 3.67 and 3.31 nM,
      respectively) agreed well with that obtained from the saturation experiments. The
      pharmacology of the site labeled by [3H]MDL 105,519 matched that of the glycine
      recognition site labeled by [3H]glycine. A strong relationship existed between
      the pKi values of a series of glycine site agonists, partial agonists and
      antagonists obtained by use of these two radioligands (r = 0.90; P < .0005; slope
      = 0.997). No effect on specific binding of [3H]MDL 105,519 was observed with
      ligands (10 microM) interacting with other sites on the NMDA receptor complex or
      with non-NMDA glutamate recognition sites.

PMID- 8858977
TI  - Inhalation exposure to volatilized opioids produces antinociception in mice.
AB  - The goal of this study was to determine whether opioids of varying potencies are
      pharmacologically active via the inhalation route of administration in mice. The
      opioids evaluated included heroin, morphine, codeine, fentanyl and meperidine;
      each of these drugs has the potential for abuse in humans. Inhalation exposure to
      each of these compounds produced antinociception in a dose-dependent manner as
      assessed in the tall-flick test. No pyrolysis products were detected after
      heating either morphine or codeine at 250 degrees C for 5 min. Although 6
      acetylmorphine was found after heating heroin, it accounted for less than 5% of
      the recovered sample. Heroin was somewhat less potent by inhalation
      administration than i.v. injection, with ED50 values of 1.6 and 0.69 mumol/kg,
      respectively. In contrast, the relative potency of morphine was substantially
      greater when inhaled than when injected, with respective ED50 values of 0.77 and
      3.9 mumol/kg. Whereas the body to brain ratios of [3H]morphine were approximately
      8 and 20 for inhalation exposure and i.v. injection, respectively, the ratio for
      heroin was approximately 5 regardless of administration route. This pattern of
      results suggests that the increase in morphine potency upon inhalation may have
      resulted from an increased accessibility to the brain compared with i.v.
      injection. Finally, naloxone reversed the antinociceptive effects of volatilized
      heroin, but neither the kappa selective antagonist nor-binaltorphimine nor the
      delta selective antagonist naltrindole blocked this antinociception, which
      suggests the involvement of mu opioid receptors. These findings taken together
      suggest the potential for the abuse of a variety of opioids, in addition to
      heroin, through the inhalation route of administration by humans.

PMID- 8858978
TI  - Central nervous system pharmacologic effect in conscious rats after intravenous
      injection of a biotinylated vasoactive intestinal peptide analog coupled to a
      blood-brain barrier drug delivery system.
AB  - Previous studies showed that intracarotid artery perfusion of biotinylated
      vasoactive intestinal peptide analog (bio-VIPa) coupled to a blood-brain barrier
      (BBB) drug delivery vector, OX26/avidin, causes an increase in brain blood flow
      by 65% in N2O-anesthetized rats. OX26 is a murine monoclonal antibody to the rat
      transferrin receptor and undergoes receptor-mediated transport through the BBB in
      vivo. The present investigation examined the central nervous system effects of
      bio-VIPa after conventional i.v. injection to conscious rats. The VIPa was
      monobiotinylated (bio) with an-XX-noncleavable (amide) linker, and the bio-XX
      VIPa conjugated to OX26/streptavidin (SA) maintained affinity for the VIP
      receptor in radioreceptor assays. Brain uptake of the bio-XX-VIPa coupled to the
      OX26/SA vector after i.v. injection was at least 10-fold higher than that of the
      free bio-XX-VIPa, because of both an increased plasma area under the
      concentration curve and BBB permeability-surface area product. Administration of
      the free bio-XX-VIPa increased salivary gland blood flow by 350%, but had no
      effect on brain blood flow. By contrast, bio-XX-VIPa/OX26-SA conjugate at equal
      doses (20 micrograms/kg) after i.v. injection increased brain blood flow by 60%
      in conscious rats, but had no effect on salivary gland blood flow. In summary,
      the use of the BBB peptide drug delivery system targeted the drug to the central
      nervous system, and optimized the therapeutic index of the VIPa by enhancing
      cerebral blood flow and by attenuating side effects in peripheral organs such as
      salivary gland.

PMID- 8858979
TI  - Endogenous tumor necrosis factor enhances topoisomerase II inhibitors activity in
      human ovarian cancer cell lines.
AB  - In this study, we demonstrated that tumor necrosis factor (TNF), secreted
      endogenously by four human ovarian cancer cell lines (A2774, IGROV-1, OVCAR-8,
      SW626), is biologically active against L929 cells and its activity is
      specifically inhibited by anti-TNF antibodies. Its endogenous production is
      increased by treatment for 24 h with phorbol myristate acetate (PMA)/ Ionomycin
      (Iono). All cell lines express TNF high-affinity receptors and release only 60
      kdalton soluble TNF receptor, both spontaneously and after stimulation with
      PMA/Iono. TNF endogenously secreted by human ovarian cancer cell lines is very
      efficient in potentiating the activity of DNA topoisomerase II inhibitors
      (doxorubicin, mitoxantrone, VP16). The activity of vinblastine and bleomycin is
      not potentiated and, more interestingly, cisplatin's activity is inhibited. In 24
      h PMA/Iono-stimulated A2774 cells, mitoxantrone specifically generated more
      cleavable complexes than in unstimulated cells. This result could provide an
      important tool in the therapy of human ovarian cancer secreting TNF protein,
      previously considered as a negative prognostic factor.

PMID- 8858980
TI  - Nitric oxide generation by renal proximal tubules: role of nitric oxide in the
      cytotoxicity of lipid A.
AB  - Lipid A, the biologically active component of lipopolysaccharide, stimulated
      nitric oxide (NO) production by isolated rat proximal tubules (as measured by NO2
      release) in a time-dependent manner. At a concentration of 50 micrograms/ml,
      lipid A stimulated NO2- generation and guanosine 3',5'-cyclic phosphate (cGMP)
      production within 5 min. Both of these effects were blocked by NG-methyl-L
      arginine (L-NMMA), an inhibitor of NO synthase or by 8-(N,N'-diethylamino)-octyl
      3,4,5-trimethoxybenzoate (TMB-8), an inhibitor of intracellular Ca++ release.
      Because an increase in NO production may be cytotoxic, we examined the cytotoxic
      potential of lipid A. At 90 min, lipid A (50 micrograms/ml) produced significant
      lactate dehydrogenase release (42 +/- 5%) compared to control (25 +/- 5%; P <
      .05). Both L-NMMA (1 mM) and TMB-8 (100 microM) completely protected against
      lipid A-induced cytotoxicity. TMB-8 but not L-NMMA inhibited the rise
      intracellular Ca++ concentration ([Ca++]i) in isolated proximal tubules elicited
      by lipid A. L-NMMA but not TMB-8 inhibited proximal tubule soluble NO synthase
      activity. Thus, in the proximal tubule, lipid A stimulates a rise in [Ca++]i that
      in turn activates constitutive NO synthase. Furthermore, these events lead
      ultimately to NO-dependent cytotoxicity. Therefore, these findings suggest the
      potential for lipopolysaccharide to have a direct impact on proximal tubule
      physiology and renal function in vivo and support the potential therapeutic
      benefits of NO synthase inhibitors in the treatment of endotoxemia.

PMID- 8858982
TI  - Enhancement of acetylcholine release by SA4503, a novel sigma 1 receptor agonist,
      in the rat brain.
AB  - We found that 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine
      dihydrochloride (SA4503), a potent and selective sigma 1 receptor agonist,
      significantly enhanced the cerebral acetylcholine (ACh) release in the rat using
      in vivo brain microdialysis technique. Interestingly, the significant enhancement
      of ACh release elicited by SA4503 was observed in the rat frontal cortex and
      hippocampus, although the striatal ACh release was unchanged. This cortical ACh
      release was fully reversed by haloperidol, a prototype sigma receptor antagonist,
      or by N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine
      monohydrochloride, a putative sigma 1 receptor antagonist. In addition, this
      enhanced ACh release by SA4503 was inhibited by tetrodotoxin, a Na+ channel
      blocker. However, tetrahydroaminoacridine, an acetylcholinesterase inhibitor,
      significantly increased the extracellular ACh level in the rat frontal cortex and
      weakly increased the hippocampal level. This compound also showed the significant
      increase of extracellular ACh level in the rat striatum. Moreover,
      tetrahydroaminoacridine markedly produced cholinomimetic side-effects, such as
      hypothermia, tremor, miosis and lacrimation. However, SA4503 did not produce
      these cholinomimetic side-effects. These findings suggest that SA4503 enhances
      the ACh release that is mediated through a novel mechanism, namely sigma 1
      receptor subtype. Furthermore, SA4503 has regional differences in the enhancement
      of cerebral ACh release, and did not produce cholinomimetic side-effects. These
      profiles are different from tetrahydroaminoacridine.

PMID- 8858981
TI  - Effects of a phorbol ester and isoquinoline sulfonamides on rabbit parietal cell
      function.
AB  - The role of protein kinase C (PKC) on gastric H+ secretion, as measured by
      aminopyrine (AP) uptake and other intracellular signal transduction products, was
      investigated in isolated rabbit parietal cells using the PKC activator 12-0
      tetradecanoyl phorbol 13-acetate (TPA) and several PKC inhibitors, including
      isoquinoline sulfonamides (H-7, H-8, H-89 and HA-1004) and calphostin-C. TPA dose
      dependently inhibited histamine (10(-4) M)- and carbachol (10(-4) M)-stimulated
      AP uptake without affecting the response to dibutyryl cyclic AMP (10(-3) M). H-7
      and calphostin-C dose-dependently augmented secretagogue-stimulated AP uptake,
      whereas H-8 and H-89 inhibited the response to secretagogues, and HA-1004 had no
      effect. H-7 and calphostin-C-induced augmentation of AP uptake was blocked by a
      calcium (Ca++) antagonist, lanthanum chloride, which suggests that the enhanced
      AP response was regulated by extracellular Ca++. Moreover, H-7 treatment
      partially reversed the TPA (10(-7) M)-induced inhibition of secretagogue
      stimulated AP uptake. TPA reduced histamine- and carbachol-stimulated cAMP and
      inositol 1,4,5-triphosphate production by 50% and 96%, respectively, with a
      concomitant reduction of adenylate cyclase and intracellular free Ca++ by 44% and
      78%. TPA increased the distribution of membrane-associated PKC by 20% and
      decreased histamine-stimulated PKA by 30%. In contrast, H-7 inhibited both PKC
      and protein tyrosine kinase activity in vitro but had no effect on these
      parameters in vivo. The results indicate that TPA-induced inhibition of
      secretagogue-stimulated AP uptake in PC is presumably mediated by activation of
      PKC.

PMID- 8858983
TI  - The inhibitory effect of angiotensin II on stimulus-induced release of cAMP is
      augmented in the genetically hypertensive rat kidney.
AB  - In the present study, with isolated perfused kidneys, we evaluated whether
      angiotensin II (Ang II) inhibits stimulus-induced release of adenosine 3',5'
      cyclic monophosphate (cAMP) and whether this effect is augmented in spontaneously
      hypertensive rats (SHR). The basal release of cAMP (in venous effluent) in the
      presence of captopril (1 mumol/l) and a phosphodiesterase inhibitor, 3-isobutyl-1
      methylxanthine (10 mumol/l), was significantly (P < .05) higher in the SHR (n =
      20) than in Wistar-Kyoto (WKY) kidneys (n = 18) although perfusion pressures were
      not significantly different in the two strains. Isoproterenol infusions (ISO;
      0.3, 1 and 3 mumol/l) significantly and similarly increased cAMP release in both
      WKY (n = 5; P < .01) and SHR (n = 6; P < .01) kidneys. A time-related attenuation
      of the cAMP response to ISO in both strains was observed in these experiments. In
      control experiments, Ang II (3 and 10 ng/min), by itself, did not significantly
      alter basal cAMP release in either strain but raised perfusion pressure in both
      SHR and WKY kidneys. In a separate set of experiments, Ang II significantly (3
      ng/min: P < .05; 10 ng/min: P < .01) inhibited ISO-induced increases in release
      of cAMP from SHR kidneys (n = 8), whereas cAMP release in response to ISO in WKY
      kidneys (n = 8) was not affected by Ang II (3 and 10 ng/min). In the same
      experiments, ISO produced small but significant decreases in perfusion pressure
      in WKY (P < .01) but not in SHR. These data clearly and directly demonstrate that
      ISO-induced increases in cAMP in the renal vasculature are similar in SHR and WKY
      rats; however, Ang II exerts a much greater negative influence on the ISO-induced
      increases in cAMP levels in the renal vasculature of SHR. The augmented
      inhibition of stimulus-induced cAMP release may be associated with an increased
      renovascular responsiveness to Ang II in SHR.

PMID- 8858984
TI  - Effects of levosimendan on myocardial contractility and oxygen consumption.
AB  - Levosimendan is hypothesized to be primarily a calcium sensitizer in vitro.
      Therefore, its inotropic action may be similar in both the normal and the
      congestive heart failure (CHF) state, and it may be associated with a decreased
      energetic cost of inotropism in vivo. To test these hypotheses, we gave
      levosimendan to cross-circulated isolated hearts from normal (n = 11) and CHF (n
      = 7, 4-week rapid pacing) dogs. Peak isovolumic left ventricular pressure at an
      end-diastolic pressure of 5 mm Hg (Pmax,5) measured by an intraventricular
      balloon was 120 +/- 15 mm Hg in normal dogs, and it was increased by
      approximately 40% in response to approximately 0.63 microM levosimendan. In CHF
      dogs, base-line Pmax,5 was only 60 +/- 12 mm Hg (P < .01 compared to normals),
      and approximately 8.4 microM levosimendan (P < .05) was required to increase
      Pmax,5 by approximately 40%. The inotropic actions were associated with increases
      in unloaded myocardial oxygen consumption by comparable amounts in normal and
      falling hearts. The blunted inotropic response in CHF and the energetic cost of
      inotropism were also comparable to those obtained with isoproterenol. In other
      studies, there was no significant inotropic action of levosimendan in Langendorff
      perfused rat hearts (n = 5), and intracellular calcium concentration, estimated
      by macroinjected aequorin, in ferret hearts (n = 2) increased dose-dependently.
      These findings suggest that inotropic actions of levosimendan in vivo may be
      mediated in part by factors other than calcium sensitization.

PMID- 8858985
TI  - Gangliosides reduce the development of ethanol dependence without affecting
      ethanol tolerance.
AB  - Mice given an ethanol-containing liquid diet, as their sole source of nutrients
      and fluid, rapidly developed functional tolerance to and physical dependence on
      ethanol. The presence of physical dependence was demonstrated by measured signs
      of central nervous system hyperexcitability upon withdrawal of ethanol. The
      withdrawal hyperexcitability, which included tremors, handling-induced seizures
      and spontaneous clonic/tonic seizures, was more pronounced when mice consumed the
      ethanol-containing diet for 7 days, compared with 5 days. Daily treatment of the
      animals with either a ganglioside mixture (extracted bovine brain gangliosides,
      250 or 500 mg/kg i.p.) or ganglioside GM1 (100 mg/kg i.p.) for the terminal two
      thirds of the ethanol administration period resulted in a significant reduction
      in the ethanol withdrawal signs. On the other hand, tolerance to the hypnotic
      action of ethanol, tested 30 hr after withdrawal of ethanol, was unaffected by
      ganglioside treatment. Ganglioside GM1 given i.c.v. at a daily dose of 10
      micrograms during the ethanol ingestion period was as effective as 100 mg/kg GM1
      given i.p. in reducing signs of ethanol withdrawal. The daily administration of
      gangliosides during the feeding of the ethanol diet did not alter the animals'
      ethanol consumption, intoxication or blood ethanol levels at the time of ethanol
      withdrawal. A single dose of GM1 given either i.p. or i.c.v. 16 hr before
      withdrawal produced no effect on the measured ethanol withdrawal signs. Our prior
      work and the work of others has demonstrated a relationship between up-regulation
      of N-methyl-D-aspartate receptor numbers in brain and the manifestation of
      ethanol withdrawal signs. Daily administration of GM1, during the last 5 days of
      a 7-day period of ethanol ingestion, prevented the up-regulation of N-methyl-D
      aspartate receptors in the hippocampus and reduced the ethanol withdrawal signs.
      Our data demonstrate that the daily administration of gangliosides during the
      period of ethanol consumption may prevent the development of ethanol physical
      dependence, while leaving ethanol tolerance intact.

PMID- 8858986
TI  - Characterization of receptor subtypes involved in prostanoid-induced conjunctival
      pruritus and their role in mediating allergic conjunctival itching.
AB  - Topically administered ketorolac (Acular), a cyclooxygenase inhibitor, has
      recently been reported as clinically beneficial for treating allergic
      conjunctivitis. The ability of ketorolac to relieve the itching associated with
      allergic conjunctivitis is intriguing because cyclooxygenase inhibitors are not
      regarded as useful in treating allergic dermatoses and prostaglandins (PG) do not
      elicit an itch response in human skin. To gain further insight into the
      mechanisms involved in the antipruritic activity of ketorolac, we used a method
      of reproducibly assessing ocular surface itch responses in the guinea pig. The
      measurement of conjunctival pruritus involved a recently developed behavioral
      model whereby hind limb scratching episodes directed toward the afflicted area
      were quantified. Itch-scratch episodes have previously been delineated from
      foreign body and pain sensations, which do not evoke such a behavioral response.
      Ketorolac significantly inhibited the itching associated with experimental
      allergic conjunctivitis. The basis of this antipruritic activity may be ascribed
      to preventing the biosynthesis of itch-producing PGs because ketorolac inhibited
      arachidonic acid-induced pruritus. In contrast to skin studies, PGE2 and PGI2
      were found to be potent pruritogens at the guinea pig ocular surface. PGD2 was a
      weak pruritogen, and PGF2 alpha and the thromboxane-mimetic U-46619 produced no
      meaningful response. Further studies involving selective agonists and antagonists
      suggested that EP1 receptors, IP receptors and PGD2-sensitive receptors may
      mediate prostanoid-induced conjunctival itching. No evidence for the involvement
      of other prostanoid receptor subtypes was obtained. Although the EP1 receptor
      antagonist AH 6809 and the DP receptor antagonist BW A868C inhibited PGE2- and
      PGD2-induced itching, respectively, neither antagonist alone significantly
      affected the itching associated with experimental allergic conjunctivitis. A
      combination of AH 6809 and BW A868C, however, did exhibit antipruritic activity.
      It appears that for effective relief of itching in allergic conjunctivitis, it is
      not sufficient to block the effects of a single pruritogenic PG. It is preferable
      to reduce the participation of all pruritogenic PGs by either using combined
      receptor antagonists or by using a cyclooxygenase inhibitor such as ketorolac to
      block their biosynthesis.

PMID- 8858987
TI  - Glycine and calcium-dependent effects of lead on N-methyl-D-aspartate receptor
      function in rat hippocampal neurons.
AB  - The effects of lead (Pb++) on N-methyl-D-aspartate (NMDA) receptor function of
      rat hippocampal neurons in culture were studied by use of the whole-cell patch
      clamp technique. Currents activated by NMDA (100 microM) in the presence of
      nonsaturating concentrations of glycine (0.01-0.05 microM) were potentiated in a
      voltage-independent manner by Pb++ (1-10 microM), and the potentiation was
      antagonized by 50 microM kynurenic acid. Increasing extracellular Ca++ from 1 to
      10 mM similarly potentiated the NMDA-activated currents in the presence of a
      nonsaturating concentration of glycine (0.2 microM). The potentiation of NMDA
      activated currents by low micromolar concentrations of Pb++ may be mediated by
      this cation's ability to increase the affinity of the NMDA receptor for glycine.
      In the presence of 10 microM glycine and 2 mM Ca++, Pb++ reduced the peak
      amplitudes of currents activated by NMDA (100 microM) in a voltage-independent
      manner (IC50 = 5.9 microM Pb++, Hill coefficient (nH) = 1.2). Also, steady-state
      currents activated by NMDA (50 microM) were inhibited by rapid application of
      Pb++ (IC50 = 3.2 microM, nH = 0.7). Increasing extracellular Ca++, in the
      presence of 10 microM glycine, reduced the NMDA-activated currents and shifted
      the Pb++ concentration-response curves to the right: at 0.2, 2 and 20 mM Ca++,
      the IC50 values of Pb++ were 3.0, 5.9 and 12.5 microM and the nH values were 0.9,
      1.2 and 1.1, respectively. The finding that external Ca++ antagonized the
      inhibitory effect of Pb++ suggests that the noncompetitive inhibitory action of
      Pb++ with respect to glycine and NMDA may be mediated by Pb++ competition with
      Ca++ for a site on the NMDA receptor.

PMID- 8858988
TI  - Inhibition of N-methyl-D-aspartate receptors by haloperidol: developmental and
      pharmacological characterization in native and recombinant receptors.
AB  - The dopaminergic antagonist haloperidol also acts at the psychotomimetic sigma
      receptor and has been proposed to act at N-methyl-D-aspartate (NMDA) receptors.
      We have investigated the basis of its action at NMDA receptors using native and
      recombinant receptors and as a function of brain development. Haloperidol
      inhibits binding of 125I-(+) MK 801 to NMDA receptors formed from NR 1a/2B with
      high affinity but has lower affinity at receptors formed from NR 1a/2A. No
      differences are noted between different NR 1 splice variants transfected with NR
      2B. Differences are also seen between neonatal receptors and adult receptors;
      neonatal receptors are inhibited by haloperidol with an IC50 value that is 50
      times lower than that of adult receptors. Other agents acting at the sigma
      receptor inhibit binding of 125I-(+) MK 801 to NMDA receptors, and are slightly
      more potent at neonatal receptors. However, the rank order of potency for sigma
      agents at sigma receptors does not match their rank order of potency at NMDA
      receptors, and the prototypic sigma ligand ditolylguanidine shows no preference
      between NR 1a/2A and NR 1a/2B receptors. This suggests that haloperidol exerts
      its effects on the NMDA receptor at a distinct site from the pharmacologically
      defined sigma receptor. The effects of haloperidol are also modified by
      spermidine noncompetitively, which differs from the effects of spermidine on
      ifenprodil-mediated inhibition of NMDA receptors. This suggests that haloperidol
      interacts with NMDA receptors at a site distinct from the polyamine or ifenprodil
      sites.

PMID- 8858989
TI  - Pharmacological advantages of conjugation of Cu, Zn-superoxide dismutase with
      succinylated keratin fragment: improvement of biological properties and
      resistance to oxidative damage.
AB  - To improve the in vivo pharmacological potential of Cu, Zn-superoxide dismutase
      (Cu,Zn-SOD), human recombinant Cu,Zn-SOD was conjugated with succinylated keratin
      fragment (Suc-ker). Suc-ker-conjugated Cu,Zn-SOD (Suc-ker-SOD) was formed by
      attachment of about 3.7 mol of Suc-ker to 1 mol of Cu,Zn-SOD and exhibited an
      apparent mean molecular weight of 107 kDa. Suc-ker-SOD exhibited 74.1% SOD
      activity on a molar basis. When Suc-ker-SOD was administered i.v. into mice, its
      plasma half-life was prolonged to 20.5 min compared with 4.7 min for native SOD.
      After i.v. administration of 51Cr-labeled proteins into mice, native SOD was
      excreted rapidly into urine and no significant accumulation was observed in
      organs other than the kidneys. On the other had, Suc-ker-SOD was taken up rapidly
      by the liver. Furthermore, Suc-ker-SOD exhibited much lower immunogenicity and
      much better therapeutic effects than native and poly(styrene-co-maleic acid)
      conjugated SOD against paraquat toxicity in mice. Moreover, the inactivation rate
      of Suc-ker-SOD by H2O2 was less than those of native SOD and polyethylene glycol
      conjugated SOD. The effect of H2O2 on liganded Cu++ in the active site of Suc-ker
      SOD was much less than those of other SOD derivatives. These results indicate
      that Suc-ker-SOD has advantages over the other SOD derivatives tested.

PMID- 8858990
TI  - Changes in opioid receptor density on murine splenocytes induced by in vivo
      treatment with morphine and methadone.
AB  - In a 24-hr time course study we reported previously that a single systemic
      injection of morphine profoundly affected various immune parameters in mice. In
      the present study we examined whether these effects are mediated by changes in
      opioid receptor density on murine splenocytes after acute in vivo morphine (20
      mg/kg s.c.) and methadone (12.5 mg/kg s.c.) at equianalgesic doses. To define the
      splenocyte subpopulations we used flow cytofluorimetric analysis with specific
      fluorescent monoclonal antibodies and calculated the binding of the fluoresceinyl
      opiate antagonist naloxone on opiate receptors. Both morphine and methadone
      reduced the density of opiate receptors on B- and T-lymphocytes. Specifically, 20
      min, 1 and 3 days after the injection there was a marked reduction (about 55%) in
      naloxone binding sites; these returned to base line after 5 days for T
      lymphocytes and after 7 days for B-lymphocytes. Despite the low proportion of
      macrophages among total splenocytes (about 10%), our results also indicate a
      tendency to a reduction in opiate receptor density also in the macrophage
      population. These findings indicate that a single exposure to morphine and
      methadone results in a strong, lasting down-regulation of opiate binding sites in
      murine splenocytes, probably accounting for the immunomodulation induced by
      opiates.

PMID- 8858991
TI  - Effect of the highly selective and nonpeptide delta opioid receptor agonist TAN
      67 on the morphine-induced place preference in mice.
AB  - The effect of 2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12, 12a alpha
      octahydroquinolino [2,3,3,-g]isoquinoline (TAN-67), a selective non-peptide delta
      opioid receptor agonist, on the morphine-induced place preference was examined in
      mice. Morphine (1-5 mg/kg, s.c.) produced a dose-related place preference in
      mice. In contrast, administration of TAN-67 (5-20 mg/kg, s.c.) did not result in
      a preference for either the drug- or vehicle-associated place. When TAN-67 (5-20
      mg/kg, s.c.) was coadministered with morphine (1 mg/kg, s.c.), the morphine
      induced place preference was enhanced dose dependently, and this effect of TAN-67
      was suppressed by the pretreatment with naltrindole (1 mg/kg, s.c.), a
      nonselective delta opioid receptor antagonist, 7-benzylidenenaltrexone (0.05 and
      0.5 mg/kg, s.c.), a selective delta 1 opioid receptor antagonist, and naltriben
      (0.05 and 0.5 mg/kg, s.c.), a selective delta 2 opioid receptor antagonist. In
      biochemical study, morphine (1 mg/kg, s.c.) or TAN-67 (20 mg/kg, s.c.) alone did
      not modify dopamine turnover in the limbic forebrain. Coadministration of TAN-67
      (20 mg/kg, s.c.) with morphine (1 mg/kg, s.c.) increased DA turnover in the
      limbic forebrain. This increase in DA turnover in the limbic forebrain was
      suppressed by pretreatment with naltrindole (1 mg/kg, s.c.) or 7
      benzylidenenaltrexone (0.5 mg/kg, s.c.), but not by naltriben (0.5 mg/kg, s.c.).
      Our results demonstrate that coadministration of TAN-67 with morphine enhances
      the morphine-induced place preference via activation of both delta 1 and delta 2
      opioid receptors, suggesting that both delta 1 and delta 2 opioid receptors may
      modulate the morphine-induced rewarding effect. In addition, we also found that
      although both delta 1 and delta 2 opioid receptors may be implicated in the
      modulation of rewarding effect of morphine, the mechanisms involved may be
      different for each receptor subtypes, i.e., mu-delta 1 interaction may mainly
      modulate the rewarding effect of morphine by enhancing neurotransmission of
      mesolimbic dopamine neurons, although modulation by mu-delta 2 opioid receptor
      interaction may involve some other dopamine-independent mechanisms.

PMID- 8858992
TI  - Effects of the androgenic/anabolic steroid stanozolol on GABAA receptor function:
      GABA-stimulated 36Cl- influx and [35S] TBPS binding.
AB  - We have recently demonstrated that androgenic/anabolic steroids modulate in vitro
      ligand binding to the benzodiazepine binding site(s) associated with the gamma
      aminobutyric acidA (GABAA) receptor complex (Masonis and McCarthy, 1995). One
      androgenic/anabolic steroid in particular, stanozolol, appears to stabilize the
      GABAA receptor in a moderate-affinity state for benzodiazepine binding. In the
      present study, we demonstrate the effects of stanozolol on the functional
      responsiveness of the GABAA receptor. After pre-incubation with stanozolol, we
      observed a decrease in the Emax and EC50 values for GABA-stimulated 36Cl- influx
      into cortical synaptoneurosomes. Moreover, in the presence of stanozolol,
      flunitrazepam-enhanced GABA-stimulated 36Cl- influx was lost, and the GABAA
      receptor was stabilized in a functional state that was resistant to further
      desensitization by agonist. Stanozolol does not appear to reduce GABA-stimulated
      36Cl- influx by acting as a channel blocker at the well-characterized channel
      blocker binding site, as illustrated by the GABA-sensitive biphasic effects of
      stanozolol on [35S] t-butylbicyclophosphorothionate binding. These results
      demonstrate a novel, nongenomic mechanism for androgenic/anabolic steroidal
      modulation of CNS function.

PMID- 8858994
TI  - Recovery of dopamine transporter binding and function after intrastriatal
      administration of the irreversible inhibitor RTI-76 [3 beta-(3p-chlorophenyl)
      tropan-2 beta-carboxylic acid p-isothiocyanatophenylethyl ester hydrochloride].
AB  - Effects of in vivo, intrastriatal administration of RTI-76 ?3 beta-(3-p
      chlorophenyl) tropan-2 beta-carboxylic acid p-isothiocyanato-phenylethyl ester
      hydrochloride?, an irreversible inhibitor of dopamine transporter (DAT) binding
      in vitro, on [125I]RTI-55 ?3 beta-[4-iodophenyl]tropan-2 beta-carboxylic acid
      methyl ester tartrate? binding to striatal DAT in vitro were examined in male
      rats. Effects on [3H]DAT and D1 dopamine receptor binding in vitro after
      intrastriatal RTI-76 injection were also determined. One hour after direct
      intrastriatal injection, RTI-76 caused a dose-related increase in KD for
      [125I]RTI-55 binding in vitro in striatal tissue, without affecting transporter
      maximum binding (Bmax). In contrast, 24 hr after administration, RTI-76 caused a
      dose-related decrease in striatal DAT Bmax without affecting KD, a decrease that
      reversed over the next several days. Transport of [3H]dopamine into synaptosomes
      was decreased similarly. Intrastriatal injection of reversible inhibitors of DAT,
      such as cocaine or WIN-35428 ?3 beta-[4-fluorophenyl]tropan-2 beta-carboxylic
      acid methyl ester tartrate), was without effect on transporter binding 1 and 6
      days after administration. RTI-76 had little effect on [3H]SCH-23390 ?R-(+)-7
      chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine? binding
      1 or 24 hr after intrastriatal injection, indicating at least some selectivity of
      RTI-76 for DAT. The RTI-76-induced decrease in Bmax, as well as the concurrent
      decrease in [3H]DAT, were reversible, with the T1/2 of transporter recovery
      estimated to be 6 days.

PMID- 8858993
TI  - Carnitine and choline derivatives containing a trimethylamine group prevent
      ammonia toxicity in mice and glutamate toxicity in primary cultures of neurons.
AB  - Carnitine prevents acute ammonia toxicity in animals. We propose that acute
      ammonia toxicity is mediated by activation of N-methyl-D-aspartate receptors and
      have shown that carnitine prevents glutamate neurotoxicity. The aim of this work
      was to assess whether other compounds containing a trimethylamine group are able
      to prevent ammonia toxicity in mice and/or glutamate toxicity in primary neuronal
      cultures. It is shown that betaine, trimethylamine-N-oxide, choline,
      acetylcholine, carbachol and acetylcarnitine prevent ammonia toxicity in mice.
      They also prevent glutamate but not N-methyl-D-aspartate neurotoxicity. Choline,
      acetylcholine and acetylcarnitine afford partial (approximately 50%) protection
      at nanomolar concentrations and nearly complete protection at micromolar
      concentrations. Trimethylamine-N-oxide, carbachol and betaine afford nearly
      complete protection at approximately 0.2 mM. The protective effect against
      glutamate neurotoxicity is prevented by 2-amino-3-phosphonopropionic acid, an
      antagonist of metabotropic glutamate receptors. Atropine, an antagonist of
      muscarinic receptors, prevents the protective effect of most of the above
      compounds against ammonia toxicity in mice and against glutamate toxicity in
      cultured neurons. These results support the idea that acute ammonia toxicity is
      mediated by activation of N-methyl-D-aspartate receptors and that glutamate
      neurotoxicity could be prevented by activating metabotropic glutamate receptors
      and/or muscarinic receptors.

PMID- 8858995
TI  - Platelet-activating factor (PAF) stimulates giant migrating contractions during
      ileal inflammation.
AB  - The role of platelet-activating factor (PAF) and substance P in stimulating
      abnormal motor activity during ileal inflammation was investigated in conscious
      dogs. All test substances were infused close-i.a. in short segments of the ileum.
      Ileal inflammation was induced by mucosal exposure to a series of ethanol and
      acetic acid infusions. In the normal state, PAF stimulated phasic contractions
      and some giant migrating contractions (GMCs), whereas substance P stimulated only
      phasic contractions. During inflammation, PAF stimulated a significantly greater
      number of GMCs, but there was no significant difference in the area under phasic
      contractions between the normal and inflamed states. Atropine, tetrodotoxin,
      hexamethonium, verapamil, diltiazem, and dantrolene significantly inhibited the
      response to PAF in both the normal and the inflamed state. By contrast,
      inhibition of nitric oxide by N omega-nitro-L-arginine methyl ester enhanced the
      contractile response to PAF. N-(6-ammohexyl)-5-chloro-1-naphtalenesulfonamide
      hydrochloride, a calmodulin antagonist, did not affect the response to PAF.
      Methacholine, neostigmine and motilin stimulated only phasic contractions during
      the normal state, but they stimulated both phasic contractions and GMCs during
      the inflamed state. We conclude that PAF is one of the inflammatory response
      mediators that may stimulate GMCs during ileal inflammation. The inflammatory
      response may modulate the enteric neuronal and cellular control of contractions
      such that the cholinergic mechanisms of stimulation of GMCs are sensitized during
      inflammation.

PMID- 8858996
TI  - Agonist potency at the cloned human beta-3 adrenoceptor depends on receptor
      expression level and nature of assay.
AB  - The cloned human beta-3 adrenoceptor was expressed in Chinese hamster ovary cells
      at three different levels (130, 400 and 3000 fmol/mg). The potency and intrinsic
      activity of a range of agonists in functional assays with these cell lines rose
      as a function of increasing receptor density. Operational analysis of
      concentration-response data allowed calculation of functional affinity and
      efficacy of agonists at the human beta-3 adrenoceptor. The data highlighted the
      low efficacy of BRL 37344 ?(RR,SS)-(+/-)-4-[(2-(2-(3-chlorophenyl)-2
      hydroxyethyl)amino)-propyl] phenoxyacetate? for the human beta-3 adrenoceptor,
      which may explain its lower potency at the human receptor despite its higher
      affinity relative to isoprenaline. The potency of catecholamines at the human
      beta-3 adrenoceptor was found to be 1 to 2 orders of magnitude higher when
      determined in an intact cell cAMP accumulation assay compared with a membrane
      based adenylyl cyclase activation assay. The reason for this enhanced sensitivity
      is not clear, but the result is that the potency of the natural agonist
      noradrenaline in the intact cell is considerably higher than predicted either
      from its ligand binding affinity, or from its potency in membrane-based assays.
      Much smaller enhancements in sensitivity were observed for compounds of the
      aryloxypropanolamine class such as CGP 12177 [(+/-)-4-(3-t-butylamino-2
      hydroxypropoxy)benzimidazol-2-one], with the result that the rank order of
      potency of such agonists at the beta-3 adrenoceptor was altered. In particular,
      CGP 12177 exhibited high relative potency in the cyclase assay, but low relative
      potency in intact cell assays. These findings highlight the importance of
      selecting appropriate expression levels and appropriate assay methodology when
      cloned receptors are used to characterize agonists.

PMID- 8858997
TI  - Species differences in the disposition and metabolism of nalidixic acid.
AB  - Nalidixic acid (NA) is an antimicrobial drug that has been used to treat urinary
      tract infections. A study of NA by the National Toxicology Program indicated that
      chronic administration in the diet at doses equivalent to 82 and 175 mg/kg/day
      for rats, and 175 and 475 mg/kg/day for mice resulted in neoplastic lesions in
      the preputial and clitoral glands of male and female Fischer 344 rats,
      respectively, but not in male and female B6C3F1 mice. Our study was designed to
      evaluate the metabolic basis of this species and tissue-dependent
      carcinogenicity. [14C]NA was administered by oral gavage as a suspension in corn
      oil at doses of 20, 200 or 500 mg/kg. Based on urinary excretion data, at least
      35 to 46 and 57 to 79% of dose was absorbed from the gastrointestinal tracts of
      mice and rats, respectively. NA-derived radioactivity was excreted primarily in
      urine and feces. The urinary and fecal metabolite profiles were species
      dependent. At 72 hr after administration, in both genders of rats and mice, the
      highest concentrations of radioactivity were observed in the liver, and the
      lowest were in the brain and adipose tissue. The preputial and clitoral glands of
      male and female rats, respectively, contained consistently and substantially
      higher concentrations of radioactivity compared to all other tissues, with the
      exception of liver. In mice, the levels of radioactivity in these tissues were
      near or below quantifiable levels. The metabolism and disposition characteristics
      of NA were linear in male and female mice over a dose range of 20 to 500 mg/kg:
      in rats, they were dose dependent. Results of this study suggest that the species
      and tissue-dependent differences in carcinogenicity of NA were associated with
      differences in metabolism and disposition between the two species.

PMID- 8858998
TI  - Rhythm anomalies related to delayed repolarization in vivo: influence of
      sarcolemmal Ca++ entry and intracellular Ca++ overload.
AB  - The present study examined how Ca++ entry and intracellular Ca++ overload may
      contribute to the appearance of torsades de pointes in the setting of delayed
      repolarization. In anesthetized rabbits, the infusion of methoxamine and the
      selective I kappa s blocker almokalant (8.8 micrograms/kg.min) was associated
      with a lengthening of the QTU interval (37 +/- 2.6 ms, P < .001) and the
      appearance of torsades de pointes in 9/10 rabbits. In rabbits pretreated with
      nisoldipine (7.7 or 37 micrograms/kg i.v.), the incidence of almokalant-induced
      torsades de pointes was reduced to 7/10 (P = .5820 vs. vehicle) and 1/10 (P =
      .0006) rabbits, respectively. This occurred without attenuating the QTU
      prolonging effect of almokalant (47 +/- 7.0 ms and 56 +/- 8.6 ms, respectively).
      Likewise, pretreatment with flunarizine (0.5 or 3.0 mg/kg i.v.) reduced the
      incidence to 1/6 (P = .0076) and 0/6 animals (P = .0009), respectively. In 10 of
      the rabbits that were given nisoldipine or flunarizine and did not experience
      torsades de pointes with almokalant, BAY K 8644 (0.11 mg/kg) was injected. In six
      of these rabbits, BAY K 8644 promptly induced torsades de pointes. In four
      vehicle-pretreated rabbits that experienced torsades de pointes with almokalant,
      acute injection of nisoldipine (37 micrograms/kg) abruptly suppressed the
      proarrhythmia. In separate experiments, rabbits were treated with ryanodine or
      BAPTA-AM and were subsequently administered almokalant. Compared with the vehicle
      pretreated rabbits, these interventions did not significantly reduce the
      incidence of torsades de pointes (from 6/5 rabbits to 3/8 and 3/8 rabbits,
      respectively, P = .1776). The results demonstrate that Ca++ entry through the L
      type Ca++ channel may be of crucial importance for the induction of torsades de
      pointes in the acquired long QT syndrome.

PMID- 8859000
TI  - Pharmacological modulation of myocardial tumor necrosis factor alpha production
      by phosphodiesterase inhibitors.
AB  - Phosphodiesterase (PDE) inhibitors are used as therapeutic agents for management
      of congestive heart failure. PDE inhibitors are potent inotropic and vasodilator
      drugs, which have also been shown to inhibit tumor necrosis factor alpha (TNF
      alpha) production. TNF-alpha is a pleiotropic cytokine that has the ability to
      produce cardiac depressant and other cardiovascular effects in many disease
      conditions. TNF-alpha levels are elevated in patients with chronic congestive
      heart failure, and it is possible that TNF-alpha may play a role in this
      condition. The effects of PDE inhibitors on TNF-alpha secretion from rat heart
      were evaluated in this study. Rat left ventricle was minced and incubated for 4
      hr with various PDE inhibitors, and the amount of TNF-alpha secretion was
      evaluated by cytotoxicity assay. Ro-20, 1724, etazolate, amrinone, milrinone and
      pentoxifylline inhibited unstimulated TNF-alpha production, with IC50 values of
      1.87, 2.07, 13.9, 153 and 201 microM, respectively. Lipopolysaccharide-induced
      TNF-alpha secretion from rat left ventricle was also evaluated in this study.
      Amrinone, milrinone and pentoxifylline inhibited lipopolysaccharide-induced TNF
      alpha secretion, with IC50 values of 14.8, 81.6 and 748 microM, respectively,
      whereas Ro-2D, 1724 and etazolate had no effect on lipopolysaccharide-induced TNF
      alpha secretion. These results demonstrated that TNF-alpha was secreted from rat
      left ventricle after 4 hr and different pharmacological manipulations were able
      to inhibit the secretion of TNF-alpha from left ventricle. These initial
      pharmacological results may provide an important tool for further investigation
      into the beneficial effects of PDE inhibitors in congestive heart failure or
      other conditions where TNF-alpha levels are elevated.

PMID- 8858999
TI  - Interleukin-5 production by peripheral blood mononuclear cells of asthmatic
      patients is suppressed by T-440: relation to phosphodiesterase inhibition.
AB  - The effect of T-440, a selective type IV phosphodiesterase inhibitor, on cytokine
      production by peripheral blood mononuclear cells (PBMC) of atopic asthmatics was
      investigated. T-440 suppressed allergen-induced interleukin (IL)-5 production
      with a high potency (IC50 = 0.039 microgram/ml) and allergen-induced
      proliferation of PBMC (IC50 = 0.30 microgram/ml). T-440 also suppressed IL-2, IL
      4 and IL-5 production by concanavalin A-activated PBMC in concentration-dependent
      manner. The IC50 values for the suppression of cytokine synthesis were 0.11
      microgram/ml for IL-2, 0.57 microgram/ml for IL-5 and 7.7 micrograms/ml for IL-4.
      cAMP-elevating agents, such as PGE2, forskolin and dibutyryl cAMP, suppressed IL
      2, IL-4 and IL-5 production by concanavalin A-stimulated PBMC in a manner similar
      to that of T-440. T-440 inhibited cAMP-phosphodiesterase activity and raised the
      intracellular cAMP level of PBMC in a concentration-dependent manner, suggesting
      that the increase of intracellular cAMP caused by T-440 results in the reduction
      of cytokine production. We conclude that T-440 suppressed cytokine production by
      peripheral T lymphocytes via the protein kinase A pathway and may be an effective
      modality to treat atopic diseases associated with eosinophilic inflammation.

PMID- 8859001
TI  - Repeated administration of the 5-HT3 receptor antagonist granisetron reduces the
      incidence of delayed cisplatin-induced emesis in the piglet.
AB  - We analyzed the effects of the 5-HT3 receptor antagonist granisetron on both
      acute and delayed phases of cisplatin-induced emesis in the conscious piglet.
      Animals that received a high dose of cisplatin (5.5 mg/kg i.v.) were observed
      continuously for 60 h. Seventeen piglets were treated with cisplatin only and
      acted as controls. In experimental animals, granisetron (administered before
      cisplatin) was administered either as a single initial injection (7 mg/kg), alone
      or in combination with dexamethasone (40 mg), or as multiple injections (1 mg/kg)
      given every 5 h during the first 30 h of the experiment (cumulative dose: 7
      mg/kg). Two other groups of piglets were treated with dexamethasone (40 mg) alone
      or with multiple injections of ondansetron (7 injections at 3.5 mg/kg),
      respectively. The latency to the first emetic episode was significantly increased
      in all groups that received a 5-HT3 receptor antagonist, whatever the agent and
      the protocol of administration. Piglets treated solely with dexamethasone
      exhibited a latency similar to that of controls. The total number of emetic
      events during the 60 h was significantly reduced only in the group of piglets
      treated repeatedly with granisetron and in the group that received an initial
      dose (7 mg/kg) of granisetron in combination with dexamethasone. We observed that
      3 out of 8 piglets treated repeatedly with granisetron did not vomit throughout
      the experiment. These results demonstrate that granisetron, when administered
      repeatedly, is efficacious against delayed emesis. They also suggest that
      serotonin may be involved in the production of the delayed phase of cisplatin
      induced emesis.

PMID- 8859002
TI  - Characterization of the prostanoid TP receptor population in human nonpregnant
      myometrium.
AB  - We have used both functional and binding studies to fully characterize the
      prostanoid TP receptor in the myometrium from nonpregnant human donors. Both U
      46,619 and I-BOP produced concentration-dependent contraction of human myometrial
      strips in vitro (pEC50 = 6.9 +/- 0.6; and 7.8 +/- 0.5, respectively). U-46,619
      induced contractions were attenuated by the TP receptor antagonists: ICI 192,605
      (pKB = 9.2 +/- 0.3); ICI D1,542 (pKB = 9.1 +/- 0.3); L670,596 (pKB = 8.6 +/-
      0.3); GR 32,191 (pKB = 8.6 +/- 0.2); SQ 29,548 (pKB = 8.2 +/- 0.5); ONO 3,708
      (pKB = 8.1 +/- 0.3) and BM 13,505 (pKB = 7.4 +/- 0.2). The binding of [125I]-BOP
      to human myometrial membranes was saturable, selective and displaceable.
      Equilibrium binding of [125I]-BOP identified one class of sites, Kd = 3.4 nM (pKd
      = 8.7 +/- 0.4) and a maximum binding of 323.1 +/- 361.5 fmol/mg protein. The
      addition of the nonhydrolyzable GTP analog GTP gamma S (100 microM) to the assay
      had no effect on [125I]-BOP binding. The Kd determined kinetically was 4.1 +/-
      0.2 nM. TP receptor antagonists competed for [125I]-BOP binding: ICI D1,542
      (pIC50 = 8.3 +/- 0.4); L670,596 (pIC50 = 7.9 +/- 0.1); ICI 192,605 (pIC50 = 7.2
      +/- 0.1); ONO 3,708 (pIC50 = 7.2 +/- 0.04); SQ 29,548 (pIC50 = 7.2 +/- 0.1); GR
      32,191 (pIC50 = 7.0 +/- 0.2); BM 13,505 (pIC50 = 6.8 +/- 0.1). The rank order of
      potency for the seven TP receptor antagonists in displacing [125I]-BOP from its
      binding site was correlated (r = 0.75) with the rank order of potency in
      inhibiting U-46,619-induced contraction of myometrial strips. Ligands selective
      for other prostanoid receptors were unable to significantly displace [125I]-BOP
      binding. These results are consistent with the notion that the human myometrial
      TP receptor is pharmacologically similar to the low affinity TP receptor in human
      platelets.

PMID- 8859003
TI  - Effects of dopamine antagonists on neuronal histamine release in the striatum of
      rats subjected to acute and chronic treatments with methamphetamine.
AB  - In this study, we examined the changes in neuronal histamine (HA) release in the
      rat striatum after acute and repeated administration of methamphetamine (METH).
      We studied the regulation of METH-induced HA release by dopamine receptors and
      the relationship between METH-induced HA release and stereotyped behavior. Acute
      administration of METH (1 mg/kg) significantly increased HA release 60 min later.
      Pretreatments with the dopamine D2 antagonists sulpiride and haloperidol blocked
      the METH-induced increase of HA release, whereas pretreatment with a dopamine D1
      antagonist, SCH23390, did not. Moreover, repeated administration of METH (3
      mg/kg) greatly enhanced the METH-induced increase of HA release 60, 80, 100, 120
      and 180 min after rechallenge of METH (1 mg/kg). Repeated treatment with
      haloperidol and METH blocked the increase of HA release induced by the
      rechallenge of METH. The METH-induced increase of HA release was still found
      after the METH-induced stereotyped behavior decreased in both acute and repeated
      administrations of METH. These findings suggest that the METH-induced HA release
      in the striatum is controlled by dopamine D2 receptors and may play an important
      inhibitory role in the METH-induced stereotyped behavior. Furthermore, a
      persistent change in the HA neuron system through DA neurotransmission may be
      partially responsible for the METH-induced behavioral sensitization.

PMID- 8859004
TI  - Effects of repeated administration of 3,4-methylenedioxymethamphetamine on 5
      hydroxytryptamine neuronal activity and release in the rat brain in vivo.
AB  - In experimental animals, administration of 3,4-methylenedioxymethamphetamine
      (MDMA, Ecstasy) leads to extensive, but incomplete, loss of 5-hydroxytryptamine
      (5-HT) innervation in the brain. Here, we report the effects of MDMA on 5-HT
      neuronal function measured in the rat in vivo using electrophysiological and
      microdialysis techniques. Two weeks after administration of an established
      neurotoxic regimen of MDMA (20 mg/kg s.c., twice daily for 4 days) we found; 1)
      no change in either the density or the firing activity of 5-HT neurons in the
      dorsal raphe nucleus; 2) no change in basal extracellular 5-HT in either the
      frontal cortex or the hippocampus, although extracellular 5-hydroxyindoleacetic
      acid was reduced by about 50% in both regions; and 3) no change in the amount of
      5-HT released in the hippocampus in response to electrical stimulation (5 Hz) of
      either the dorsal or medial raphe nucleus, but a marked reduction in the amount
      of 5-HT released in the frontal cortex after electrical stimulation of the dorsal
      raphe nucleus. In summary, although MDMA causes marked 5-HT neurotoxicity, our
      data suggest that 5-HT cell firing is unchanged and, furthermore, that 5-HT
      release is maintained in some (but not all) forebrain regions even in response to
      physiological levels of stimulation.

PMID- 8859005
TI  - Disposition of oligonucleotides in isolated perfused rat kidney: involvement of
      scavenger receptors in their renal uptake.
AB  - The objective of this study was to clarify the renal disposition characteristics
      of a 20-mer model phosphodiester oligonucleotide and its partially (PS3) and
      fully (PS) phosphorothioated derivatives, in isolated rat perfused kidney. Venous
      outflow and urinary excretion pattern, as well as tissue accumulation of
      radioactivity after bolus injection of 32P-labeled oligonucleotides, were
      evaluated under both filtering and nonfiltering conditions. The binding affinity
      of oligonucleotides to bovine serum albumin in the perfusate increased as the
      number of sulfur atoms present in the oligonucleotide molecules increased,
      resulting in 21, 60 and 86% binding to bovine serum albumin for phosphodiester
      oligonucleotide, PS3 and PS, respectively. The apparent steady-state distribution
      volumes of the oligonucleotides, as calculated from the venous outflow patterns,
      were larger than that of inulin, which corresponds to the extracellular volume of
      the kidney, suggesting their interaction with tissue from the vascular space. PS
      showed the largest distribution volume. Urinary excretion of oligonucleotides was
      greatly restricted, compared with that of inulin, which was used as a marker of
      glomerular filtration rate. The accumulation of these oligonucleotides was
      ascribed to both tubular reabsorption and uptake from the capillary side. The
      uptake of oligonucleotides from the capillary side increased as the number of
      sulfur atoms present in the molecules increased, suggesting sulfur atom-dependent
      interactions between oligonucleotides and renal tissue. In addition, the uptake
      of PS3 was a saturable process. Furthermore, coadministration of dextran sulfate
      and polyinosinic acid inhibited the renal uptake of PS3, whereas polycytidic acid
      and 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid did not,
      suggesting that oligonucleotides were taken up via the scavenger receptor
      mediated process for polyanions. These findings provide valuable information for
      the development of delivery systems for antisense oligonucleotides.

PMID- 8859006
TI  - The systemic and cerebral kinetics of thiopental in sheep: enantiomeric analysis.
AB  - Thiopental is used as a racemate (rac-thiopental). Enantiomeric pharmacokinetic
      differences could therefore influence the onset and duration of anesthesia of rac
      thiopental. We studied the systemic and cerebral kinetics of R(+)- and S(-)
      thiopental in five adult ewes after a 2-min intravenous infusion of 500 mg rac
      thiopental sodium. Systemic kinetic values were determined from the time course
      of concentrations in arterial plasma; cerebral kinetic values were deduced from
      the time course of the concentration differences between arterial and superior
      sagittal sinus blood plasma. Enantiomeric differences were found in both sites,
      with the (R:S) ratio of thiopental enantiomer blood concentrations initially
      being > or = 1 then decreasing to < 1 after approximately 60 min. This is
      consistent with the finding of the mean total body clearance of R(+)-thiopental
      being 17% (SD 12%) greater than that of S(-)-thiopental (P = .04). Sagittal sinus
      plasma concentrations of both enantiomers followed closely behind those in
      arterial plasma and this is consistent with facile bidirectional exchange of
      thiopental between plasma and brain. No significant differences were found
      between enantiomers in the rates of brain influx or efflux. Onset and regression
      of anesthesia occurred while the enantiomer blood concentrations were similar.
      Hence published pharmacokinetic-pharmacodynamic models of the onset of thiopental
      effects probably are not significantly compromised by neglecting the enantiomeric
      duality of thiopental, but models based on its elimination kinetics could be
      compromised if enantiomeric differences are neglected.

PMID- 8859007
TI  - Advantages of raloxifene over alendronate or estrogen on nonreproductive and
      reproductive tissues in the long-term dosing of ovariectomized rats.
AB  - For the first time, raloxifene or alendronate was administered to rats
      immediately after ovariectomy for 10 months and compared with estrogen to
      elucidate mechanisms behind the raloxifene effects observed in nonreproductive
      and reproductive tissues. Specifically, 75-day-old rats were randomly selected as
      sham controls (Sham), ovariectomized controls (Ovx) or ovariectomized rats
      treated with fully efficacious doses of raloxifene (RA), 17 alpha-ethynyl
      estradiol (EE2) or alendronate (ABP). Lumbar vertebrae and proximal tibiae were
      examined by computed tomography (QCT) and by histomorphometry. Histomorphometry
      showed differences in bone architecture between groups when QCT densities were
      similar, but tibial trabecular bone analysis by QCT correlated with
      histomorphometry with r = .86 to .93, depending on the parameter. Both techniques
      confirmed that Ovx had substantially less bone than Sham, with greater loss of
      trabecular bone in the proximal tibia than vertebrae. Both techniques showed that
      RA had effects similar to but not identical with EE2 in preventing bone loss in
      vertebrae and tibiae. ABP partially prevented loss of bone in L-5, but was not
      significantly different from Ovx in the proximal tibia. This may be caused by ABP
      suppression of bone apposition, beyond effects observed for EE2 or RA. RA
      appeared to be more similar to EE2 because ABP significantly depressed bone
      formation (bone formation rate, mineral apposition rate) to below RA or EE2
      levels, especially in L-5. Mechanical loading to failure of L-6 vertebrae showed
      a rank order of vertebral strength of Sham > RA > EE2 > Ovx > ABP, although
      significant differences were not observed between treatment groups. These data
      show that ABP suppression of bone formation can affect bone quality with long
      term treatment. In other tissues, RA had minimal uterine effects, while
      significantly lowering serum cholesterol to below EE2-treated levels. Both EE2
      and RA rats had significantly lower body weights than the other groups. ABP had
      no effect on serum lipids, uterine weight or body weight. Therefore, RA appears
      to have a broader range of desirable effects on bone, body weight, uteri and
      cholesterol than ABP or EE2 in ovariectomized rats.

PMID- 8859008
TI  - Mechanisms of action of cholecystokinin in the canine gastrointestinal tract:
      role of vasoactive intestinal peptide and nitric oxide.
AB  - This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which
      CCK octapeptide (CCK8) and gastrin 17 (G17)act on motor functions of the intact
      canine gastrointestinal tract. In the antrum, studies of tachyphylaxis and
      effects of antagonists showed that i.a. G17 acted through CCKB receptors to
      activate contractions, whereas CCK8 acted through A and B receptor subtypes to
      produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition
      of electrical field-stimulated contractions, apparently by release of nitric
      oxide [blocked by N-nitro-L-arginine (L-NNA) or NG-L-arginine methyl ester].
      These inhibitory effects were abolished by YM022 (a CCKB antagonist) but not by L
      364, 718 (a CCKA antagonist). However, i.a. CCK8 increased electrical field
      stimulated contractions and L-364, 718 reversed this effect. In isolated perfused
      segments of distal intestine, CCK8 caused inhibition and excitation and released
      vasoactive intestinal peptide (VIP) into the venous effluent. CCK tetrapeptide
      and G17 had inconsistent effects. Excitation and VIP release were inhibited by L
      364, 718. L-NNA potentiated excitatory responses and abolished inhibitory
      responses. Tetrodotoxin and atropine abolished and hexamethonium reduced
      excitatory responses to CCK8, but L-NNA restored contractions after atropine
      treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK8
      still enhanced it. L-364, 718 abolished hexamethonium-resistant contractions and
      VIP release. Thus, CCK/gastrin peptides act on neural receptors in intact canine
      gastrointestinal tract. In antrum, activation of neural CCKA or CCKB receptors
      initiates contractions. In intestine, CCKA receptors at pre- and postjunctional
      sites in enteric nerves mediate acetylcholine and VIP release. CCKB receptors
      mediate release of an inhibitory mediator, apparently nitric oxide, from
      postjunctional sites.

PMID- 8859009
TI  - Proarrhythmic actions of flecainide in an isolated tissue model of ischemia and
      reperfusion.
AB  - Flecainide may increase the incidence of cardiac arrhythmias in acute ischemia.
      The objective of this study was to determine the cellular actions underlying this
      effect in an isolated tissue model of acute ischemia and reperfusion.
      Transmembrane electrical activity was recorded with conventional microelectrode
      techniques from epi- and endocardial surfaces of right ventricular free walls
      from guinea pig hearts. Endocardium was stimulated. Tissues were equilibrated in
      Tyrode's solution for 60 min, then exposed to simulated ischemia (hypoxia,
      acidosis, lactate, hyperkalemia, no glucose) for 15 min and reperfused with
      normal Tyrode's solution for 30 min. In the absence of flecainide, sustained and
      nonsustained ventricular tachycardia occurred in 78% of hearts during ischemic
      conditions and 78% in early reperfusion (n = 14). Premature beats occurred in 14%
      of hearts in early reperfusion. Ventricular tachycardia was associated with
      abbreviation of endocardial effective refractory period and action potential
      duration, plus prolongation of transmural conduction time. Flecainide abolished
      premature beats at a concentration of 1 mumol/l or higher. However, an increase
      in the incidence of ventricular tachycardia occurred in both ischemia and
      reperfusion at all concentrations of flecainide (0.03-10.0 mumol/l).
      Proarrhythmic effects of flecainide were associated with selective prolongation
      of transmural conduction time in ischemia and early reperfusion. In epicardial
      slices flecainide lengthened conduction time transverse, but not parallel to
      fiber orientation. Our results suggest that proarrhythmic effects of flecainide
      in acute ischemia and reperfusion are mediated by potentiation of the
      arrhythmogenic effects of ischemia on anisotropic properties of the myocardium.

PMID- 8859010
TI  - Evaluation of cerebral pharmacokinetics of the novel antidepressant drug, BMS
      181101, by positron emission tomography.
AB  - BMS-181101 is a novel antidepressant drug that is currently under clinical
      investigation. The goal of this study was to evaluate the pharmacokinetics and
      receptor binding of this agent in the brains of healthy human volunteers. BMS
      181101 was radiolabeled with 11C by methylation with [11C]CH3I of the 5
      hydroxypiperazine precursor and the product was purified by high-performance
      liquid chromatography. Cerebral pharmacokinetics of [11C]BMS-181101 were studied
      by dynamic positron emission tomography imaging in six healthy volunteers. Two
      studies were performed in each subject. For the first study the subject was
      injected with 10 mCl of high specific activity [11C]BMS-181101 (approximately
      1700 mCi/mumol) and serial positron emission tomography images and arterial blood
      samples were collected over 90 min. Thirty minutes after acquiring the final
      image, each subject was coinjected with a second dose, 10 mCi of [11C]BMS-181101
      plus 3 mg of unlabeled drug (final specific activity approximately 1.5
      mCi/mumol), and imaging/blood collection was repeated. The data were analyzed by
      calculating regional tracer accumulation (percent injected dose/g) at 60 min
      after injection and compartmental modeling. Measurements of percent injected
      dose/g yielded similar values for all brain regions, independent of specific
      activity. Kinetic modeling of time activity curves for cerebellum, caudate,
      putamen, thalamus, pons and temporal, occipital and frontal cortex demonstrated
      that tissue distribution can be described by a simple two-compartment flow model.
      Statistical comparisons of the apparent distribution volumes for each region
      failed to reveal significant differences between the high and low specific
      activity studies. These results indicate that the central nervous system
      distribution of [11C]BMS-181101 is dominated by blood flow and significant
      receptor-specific localization does not occur in any brain region.

PMID- 8859011
TI  - Hypothermia and metabolic stress: narrowing the cellular site of early
      neuroprotection.
AB  - In a previous study we showed that hypothermia of 30 degrees C can expand the
      time during which retinal neurons in vitro can have their metabolism inhibited
      without adverse effects. In isolated chick retinae, the first signs of acute
      toxicity resulting from mild, partial, pharmacological inhibition of metabolism
      are N-methyl-D-aspartate (NMDA)-mediated histological swelling and gamma
      aminobutyric acid release. More prolonged or severe inhibition of metabolism
      results in involvement of non-NMDA glutamate receptors and voltage-dependent Na+
      channels. In this study we examine early cellular events that may be associated
      with hypothermic protection. The early cellular events thought to follow
      metabolic stress involve a decrease in ATP, reduced activity of the Na+, K(+)
      ATPase, which renders ion leakage unopposed, degradation of the membrane
      potential and subsequent activation of ionotropic glutamate receptors and voltage
      dependent Na+ channels, which leads to acute toxicity. Reduction by hypothermia
      of the rate of loss of ATP was shown, In past work, to only partially account for
      neuroprotection. In the present study, inhibition of the Na+, K(+)-ATPase with 10
      microM ouabain for 30 min at 37 degrees C led to acute toxicity that was similar
      to the toxicity produced by severe metabolic stress, i.e., primarily excitotoxic
      and mediated by NMDA receptors and secondarily involving non-NMDA receptors and
      voltage-dependent Na+ channels. Swelling and increased gamma-aminobutyric acid
      release were first evident at 15 min of incubation with ouabain at 37 degrees C.
      Hypothermia (30 degrees C) delayed the onset of acute excitotoxicity caused by
      ouabain. This protection was independent of an involvement with ATP loss, because
      ouabain treatment did not reduce ATP levels. Protection against ouabain suggests
      that hypothermia can intervene at steps subsequent to decreased Na+, K(+)-ATPase
      activity. In contrast, reducing the temperature to 30 degrees C did not attenuate
      NMDA-mediated secondary excitotoxicity caused by lowering of the membrane
      potential with increasing extracellular K+ concentrations (32-55 mM). However,
      hypothermia of 30 degrees C was able to reduce the rate of ouabain-induced 86Rb
      efflux. The findings described above suggest that a critical site of action for
      hypothermic protection is at a step between decreased Na+, K(+)-ATPase activity
      and degraded membrane potential, specifically, slowing of the rate of ion
      leakage.

PMID- 8859013
TI  - Corticotropin-releasing factor and type 1 corticotropin-releasing factor receptor
      messenger RNAs in rat brain and pituitary during "binge"-pattern cocaine
      administration and chronic withdrawal.
AB  - Endogenous central corticotropin-releasing factor (CRF) may be involved in the
      neuroendocrine and behavioral responses to cocaine. In the present study, levels
      of CRF mRNA were measured in the hypothalamus and in several extrahypothalamic
      brain regions after different regimens of "binge"-pattern cocaine administration.
      Male Fischer rats were injected with saline or cocaine (15 mg/kg, 1 hr x 3/day)
      at the beginning of the light cycle, to approximate the manner in which cocaine
      is often abused by humans, both in terms of temporal pattern and in relation to
      circadian rhythm. Cocaine administered in this binge regimen produced time
      dependent alterations of CRF mRNA levels in the hypothalamus. There was a
      significant increase in CRF mRNA levels on day 1, which returned to base-line
      levels on day 2, with elevated plasma corticosterone levels on both days. CRF
      receptor type 1 and prooplomeianocortin mRNA levels in the anterior lobe of the
      pituitary were not significantly altered after acute cocaine injections on day 1
      or day 2. On day 14 of chronic binge-pattern cocaine administration, decreased
      hypothalamic CRF mRNA levels and an attenuated elevation in plasma corticosterone
      levels were found. After 10 days of withdrawal from 14-day binge cocaine, CRF
      mRNA returned to basal levels. CRF mRNA levels in the amygdala were also
      significantly increased on day 1 and returned to basal values on day 2. Chronic
      (14-day) binge cocaine administration did not alter CRF mRNA levels in the
      amygdala. These results suggest that the attenuated response in the hypothalamic
      pituitary-adrenal axis to chronic binge cocaine administration is coupled to the
      cocaine-induced decreases in CRF gene expression in the hypothalamus and that
      activation of CRF gene expression in extrahypothalamic regions may have
      implications for a molecular understanding of the behavioral responses to
      cocaine.

PMID- 8859012
TI  - Soluble cytokine receptors as carrier proteins: effects of soluble interleukin-4
      receptors on the pharmacokinetics of murine interleukin-4.
AB  - Soluble interleukin-4 (IL-4) receptors (sIL-4R) can have either enhancing or
      inhibitory effects on the activity of IL-4 in vivo, depending on the relative
      concentration ratios of sIL-4R to IL-4. Whereas competition with membrane IL-4
      receptors is the basis for their inhibitory action, the mechanisms responsible
      for the potentiation of IL-4 activity are not completely clear but may involve
      alterations in the half-life and biodistribution of IL-4 in vivo. To better
      understand the basis for the enhancing effect of sIL-4R, we have analyzed their
      effects on the pharmacokinetic properties of IL-4. Studies with radiolabeled
      recombinant IL-4 demonstrated that, when injected alone, IL-4 was rapidly cleared
      from the circulation and eliminated through the kidneys in a proteolytically
      degraded form. Administration of IL-4 in combination with increasing
      concentrations of sIL-4R resulted in a dose-dependent enhancement in the blood
      levels of IL-4 and a concomitant reduction in its clearance from circulation and
      excretion in the urine. Differences between measurements of IL-4 concentrations
      based on radioactivity and enzyme-linked immunosorbent assays indicated that the
      injected IL-4 was rapidly inactivated in vivo and that the presence of sIL-4R
      diminished this process. The inactivation of IL-4 was mediated through the
      membrane IL-4 receptors and required receptor internalization and intact
      lysosomal function. Taken together, these results suggest that sIL-4R are able to
      alter the pharmacokinetic properties of IL-4, prolonging its half-life in the
      circulation and reducing its clearance through diminished renal excretion and/or
      interference with inactivation. These effects are consistent with the ability of
      sIL-4R to potentiate IL-4 activity in vivo.

PMID- 8859014
TI  - Cocaine-induced peroxidative stress in rat liver: antioxidant enzymes and
      mitochondria.
AB  - This study investigated how the cocaine-induced lipid peroxidation affected liver
      antioxidant enzymes and mitochondria. Acute cocaine (40 mg/kg) injection produced
      a significant, time-dependent increase in manganese-superoxide dismutase (Mn/SOD)
      activity and cellular thiobarbuturic acid reactive substances (TBARS), but
      activities of glutathione peroxidase and catalase were reduced significantly.
      These changes coincided with increased production of reactive oxygen species by
      mitochondria and decreased cellular ATP and glutathione. Binge cocaine (25 mg/kg;
      5 injections in 3 days) significantly increased TBARS and conjugated dienes, but
      decreased ATP and glutathione. Accumulation of TBARS and reduction of glutathione
      was seen in mitochondria. Activities and mRNA of Mn/SOD and copper-zinc
      superoxide dismutase were significantly elevated, but mRNA and activities of
      glutathione peroxidase and catalase were decreased in cocaine-treated rats.
      Cocaine (binge model) produced scattered liver necrosis (20%) and compromised
      cell integrity. This is the first report demonstrating cocaine-induced liver
      necrosis in rats. Pretreatment (acute model) with dimethylaminoethyl-2,2
      diphenylvalerate, inhibitor of cocaine bioactivation, curtailed in part the
      generation of reactive oxygen species by mitochondrial fraction.
      Dimethylaminoethyl-2,2-diphenylvalerate also prevented the increase of TBARS and
      Mn/SOD. The results suggest that elevated levels of Mn/SOD and copper-zinc
      superoxide dismutase, without a concomitant increase in glutathione peroxidase,
      catalase and glutathione s-transferase, may have contributed to cocaine-induced
      cellular and mitochondrial peroxidative stress. Reactive metabolites of cocaine N
      oxidative metabolism may be responsible for the cocaine-induced oxidative stress
      and liver necrosis.

PMID- 8859015
TI  - Stable expression and characterization of recombinant human heteromeric N-methyl
      D-aspartate receptor subtypes NMDAR1A/2A and NMDAR1A/2B in mammalian cells.
AB  - The electrophysiological and pharmacological properties of two mammalian cell
      lines stably transfected with cDNAs encoding recombinant human N-methyl-D
      aspartate (NMDA) receptor subtypes NMDAR1A/2A and NMDAR1A/2B are described. In
      whole-cell electrophysiological recordings, application of NMDA/glycine elicited
      inward currents at negative holding potentials in human NMDAR1A/2A (hNMDAR1A/2A)-
      and hNMDAR1A/2B-expressing cells. The current-voltage relationships determined in
      both cell lines in the presence and absence of external Mg++ were similar to
      those observed with recombinant rat NMDA receptors. Power spectra calculated from
      NMDA/glycine-induced currents for both NMDA receptor-expressing cell lines
      suggested a kinetically homogeneous population of channels. Immunoprecipitation
      with an anti-NMDAR1A antibody coprecipitated the corresponding NMDAR2 subunit
      with the NMDAR1A, suggesting that heteromeric complexes are formed in these
      stable cell lines. Stimulation of NMDA receptors evoked an increase in
      intracellular Ca++, which was used to characterize their pharmacological
      properties. NMDA displayed less intrinsic activity than did glutamate in both
      NMDA receptor-expressing cell lines and was a 4-fold more potent agonist at
      hNMDAR1A/2B than hNMDAR1A/2A. NMDA/glycine-evoked increases in Ca++ levels were
      inhibited by CGS 19755, (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate, MK
      801, ketamine and ifenprodil. (+/-)-3-(2-Carboxypiperazin-4-yl)propyl-1
      phosphonate was a 3-fold more potent antagonist at hNMDAR1A/2A than hNMDAR1A/2B,
      whereas ifenprodil was markedly more selective toward hNMDAR1A/2B, being 250-fold
      more potent than against hNMDAR1A/2A. These data suggest that cells stably
      expressing recombinant heteromeric hNMDAR1A/2A and hNMDAR1A/2B represent
      pharmacologically valid experimental systems to study human NMDA receptors.

PMID- 8859016
TI  - Neural stimulation of Egr-1 messenger RNA expression in rat adrenal gland:
      possible relation to phenylethanolamine N-methyltransferase gene regulation.
AB  - Metrazole, which reflexively activates the splanchnic nerve to the adrenal
      medulla, was used to investigate the physiological role of Egr-1 in the neural
      regulation of phenylethanolamine N-methyltransferase (PNMT) gene transcription in
      the rat adrenal gland. A single dose of this drug (70 mg/kg s.c.) rapidly and
      transiently induced Egr-1 mRNA, with a maximum 22.0-fold increase at 30 min after
      treatment, followed by a 3.7-fold increase in PNMT mRNA at 8 hr. In contrast,
      cocaine (15 mg/kg i.p.), which activates the hypothalamic-pituitary-adrenal axis,
      increased Egr-1 mRNA only 3-fold at 30 min, although it elevated PNMT mRNA
      comparably. Consistent with their mechanisms of activation, cocaine increased
      corticosterone levels 7.7-fold at 30 min, whereas metrazole modestly elevated
      this endogenous corticosteroid 2.5-fold. The cholinergic agonists nicotine (2
      mg/kg l.p.) and muscarine (0.1 mg/kg i.p.) also elevated Egr-1 mRNA, with a peak
      12- to 15-fold increase being apparent at 30 min after treatment, followed by a
      1.7-to 2.0-fold rise in PNMT mRNA at 8 hr. In vitro, metrazole did not increase
      Egr-1 mRNA above levels observed with carbachol alone (100 microM) in PC-12
      derived RS1 cells pretreated with this cholinergic agonist. Finally, splanchnic
      denervation partially blocked the metrazole-induced rise in Egr-1 mRNA (50%
      control), while having no effect on cocaine-induced changes in Egr-1 mRNA. These
      results provide further support for the involvement of Egr-1 in the neural
      regulation of PNMT gene expression in the rat adrenal gland.

PMID- 8859017
TI  - Ontogeny and hormonal basis of female-dominant rat hepatic sulfotransferases.
AB  - Female-dominant sulfotransferases (ST) are a group of enzymes catalyzing
      sulfation of steroid hormones, bile acids and exogenous carcinogens. To
      understand the regulation of these enzymes, developmental and hormonal regulation
      of three female-dominant ST was studied. The three ST, ST-20/21, ST-40/41 and ST
      60, were differentiated by specific oligonucleotide probes, and their gene
      expression was examined by Northern-blot analyses. The three ST have different
      developmental patterns, as ST-20/21 and ST-60 were increased after puberty in
      female rats, although ST-40/41 was higher in immature rats. In addition, ST-20/21
      and ST-60 expression reached a peak at 30 days of age in male rats, although ST
      40/41 reached its highest value in male rats at 15 days of age. Estrogens and
      androgens did not appear to be major determinants of the developmental profiles.
      However, ST-20/21 was decreased in both male and female rats by hypophysectomy,
      and reversed by continuous infusion (female pattern) of growth hormone (GH). In
      contrast, hypophysectomy elevated ST-40/41 and ST-60 expression in males. The
      elevation in males was reversed by GH injection (male pattern). This study
      demonstrates that the three female-dominant sulfotransferases display two
      ontogenic patterns and are regulated by different mechanisms. Female GH secretory
      pattern appears to determine the high expression of ST-20/21 in postpubertal
      female rats, although male GH secretory pattern results in the low expression of
      ST-40/41 and ST-60 in mature male rats.

PMID- 8859018
TI  - Differential effects of intra-accumbens sulpiride on cocaine-induced locomotion
      and conditioned place preference.
AB  - The effects of intra-accumbens sulpiride on conditioned place preference and
      locomotion produced by i.v. cocaine were investigated. Every other day during
      conditioning, rats received infusions of sulpiride (0-0.4 microgram) into the
      nucleus accumbens (NAc) or caudate-putamen. Fifteen min later, they were placed
      into a distinct compartment and injected with saline or cocaine (4.2 mg/kg,
      i.v.). On the alternate days, rats received sham intracranial injections and were
      placed into a different compartment. Locomotion and stereotypies were assessed
      after the first and last injection, and conditioned place preference was assessed
      24 hr after the last conditioning day. After behavioral testing, receptors
      occupied by sulpiride were quantified by injecting rats intracranially with their
      respective dose of sulpiride, followed by a systemic injection of the
      irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).
      Receptors protected from EEDQ induced inactivation by sulpiride were revealed on
      autoradiograms of sections labeled with 3H-sulpiride. Sulpiride did not alter
      cocaine-conditioned place preference or cocaine-induced stereotypies. However,
      the two lowest doses of intra-accumbens sulpiride attenuated cocaine-induced
      locomotion and occupied > 42% of the sulpiride binding sites in the NAc, and the
      highest dose completely reversed cocaine-induced locomotion and occupied > 96% of
      the sulpiride binding sites in the NAc. Intracaudate sulpiride also attenuated
      cocaine-induced locomotion without occupying a significant number of binding
      sites in the NAc. These findings suggest that D2-like receptors in the NAc and
      anterior medial caudate-putamen are involved in cocaine-induced locomotion, but
      not cocaine-conditioned place preference.

PMID- 8859019
TI  - Inhibitory mechanism of CO2 inhalation on slowly adapting pulmonary stretch
      receptors in the anesthetized rabbit.
AB  - The inhibitory effects of CO2 on slowly adapting pulmonary stretch receptors
      (SARs) were studied before and after administration of acetazolamide, a carbonic
      anhydrase inhibitor, or nifedipine, a calcium channel blocker, in anesthetized,
      artificially ventilated rabbits after vagus nerve section. CO2 inhalation
      (maximal tracheal CO2 concentration ranging from 7.2% to 9.5%) for approximately
      60 sec decreased the receptor activity during both inflation and deflation. The
      magnitude of decreased receptor activity during deflation became more pronounced
      than that seen during inflation. Acetazolamide treatment (20 mg/kg) diminished
      the inhibitory responses of slowly adapting pulmonary stretch receptors to CO2
      inhalation, which were not significantly influenced by pretreatment with
      nifedipine (1 mg/kg). Furthermore, CO2 inhalation before and after vagal
      denervation had no effect on total lung resistance and dynamic lung compliance.
      In another series of experiments, the staining to determine the presence of
      carbonic anhydrase enzymatic reaction was not found in the smooth muscle of
      either extrapulmonary or intrapulmonary bronchi. These results suggest that CO2
      induced inhibition of slowly adapting pulmonary stretch receptors is not related
      to the change in bronchomotor tone.

PMID- 8859020
TI  - Glutamate ameliorates experimental vincristine neuropathy.
AB  - The dose-limiting toxicity of the chemotherapeutic agent vincristine is
      peripheral neuropathy, for which there is no established therapy. The amino acid
      glutamate has been proposed as a neuroprotectant for vincristine, but a full
      preclinical evaluation of its efficacy, safety and mechanism of action has been
      hampered by a lack of suitable animal models. We report the development of a Dark
      Agouti rat model of sensorimotor peripheral neuropathy, to investigate the
      neurotoxicity of cytotoxic drugs. Neuropathy was manifested as gait disturbance
      in 100% of vincristine-treated animals (n = 12), significant elevation of the
      tail-flick threshold (5.1 +/- 2 sec) and significantly impaired mean Rotarod
      times (55 +/- 41 sec) developing after administration of 1.5 mg/kg vincristine
      over 2 weeks. Among vincristine-treated animals supplemented p.o. with sodium
      glutamate (500 mg/kg/day in drinking water) from 24 hr before vincristine
      treatment, only one (8%, P = .01) developed gait disturbance, the tall-flick
      threshold was not significantly different from controls and the mean Rotarod
      score was 188 +/- 18 sec (P = .004). Glutamate thus significantly protected
      against both sensory and motor neuropathy. We observed no intrinsic neurotoxicity
      with glutamate and no interference with the cytotoxic efficacy of vincristine
      against a transplantable rat mammary adenocarcinoma grown s.c. in Dark Agouti
      rats. Our findings suggest that glutamate is likely to be a safe and effective
      neuroprotectant for patients receiving vincristine, and it warrants further
      clinical evaluation. The mechanism of this selective neuroprotection by glutamate
      remains to be elucidated. Our rat model may be of use in determining whether
      glutamate offers protection from other neurotoxic drugs.

PMID- 8859021
TI  - In vitro inactivation of human O6-alkylguanine DNA alkyltransferase by antitumor
      triazene compounds.
AB  - The cytotoxic and mutagenic properties of antitumor triazene compounds (TZC) have
      been mainly attributed to their ability to form DNA adducts at the O6 position of
      guanine. Repair of these lesions is mediated by O6-alkylguanine DNA
      alkyltransferase (OGAT) in an autoinactivating reaction. Therefore when lesion
      repair has occurred, cells are depleted of OGAT until synthesis of new enzyme
      molecules takes place. In this study, we have evaluated the ability of DNA
      alkylated by different TZC to deplete OGAT activity. Moreover, we have also
      investigated whether these compounds might inactivate the OGAT enzyme by a direct
      reaction with the protein. Human OGAT protein was partially purified from insect
      cells infected with a recombinant baculovirus containing the human OGAT coding
      sequences. Thereafter human OGAT protein was exposed directly to TZC or to TZC
      alkylated DNA. Among the TZC tested, p-(3-methyl-1-triazeno)benzoic acid was the
      most effective OGAT inactivator by direct interaction with the protein. Moreover
      DNA substrates treated with methylating TZC, such as temozolomide or p-(3-methyl
      1-triazeno)benzoic acid, were more effective in depleting the repair enzyme,
      compared to DNA pretreated with the chloroethylating TZC mitozolomide. In
      conclusion, our results show that TZC inactivate in vitro OGAT activity by either
      direct or indirect mechanisms. Therefore TZC are good candidates for 1)
      increasing their own cytotoxicity, if used according to appropriate dose and
      treatment schedules and 2) reversing tumor cell resistance to O6-guanine
      alkylating agents.

PMID- 8859022
TI  - Radioligand binding, autoradiographic and functional studies demonstrate
      tachykinin NK-2 receptors in dog urinary bladder.
AB  - Tachykinin receptors in the dog bladder were characterized using radioligand
      binding, functional and autoradiographic techniques. In detrusor muscle
      homogenates, specific binding of [125l]iodohistidyl neurokinin A (INKA) and
      [125l]Bolton Hunter eledoisin was reversible, saturable and, to a single class of
      sites of Kd, 3,6 and 27 nM, respectively. No specific binding of [125l]Bolton
      Hunter[Sar9, Met (O2)11] substance P occurred. INKA binding was reduced by the
      peptidase inhibitor bacitracin. The rank potency order of agonists competing for
      binding of both radioligands indicated interaction at NK-2 sites. NK-2-selective
      antagonists also competed for INKA binding, with SR 48968, GR 94800, MDL 29913
      and the selective agonist [Lys5, MeLeu9, Nle10]-NKA(4-10) showing biphasic
      binding profiles. Autoradiographic studies revealed specific binding of INKA and
      [125l]Bolton Hunter eledoisin over detrusor muscle and small arteries.
      [125l]Bolton Hunter [Sar9, Met (O2)11] SP labeled the intima of arteries and
      arterioles, but not the detrusor muscle. Tachykinins contracted detrusor muscle
      strips, with potency order at the carbachol EC15 NKA = kassinin > [Lys5, MeLeu9,
      Nle10]-NKA(4-10) = neuropeptide gamma = neuropeptide K = NKB > > MDL 28564, with
      [Sar9, Met(O2)11]-SP ineffective. Shallow concentration-response curves, variable
      efficacies and inhibition by atropine and mepyramine suggest that other
      mechanisms may influence contractile responses. Responses to [Lys5, MeLeu9,
      Nle10]-NKA(4-10) were inhibited competitively by MDL 29913 and MEN 10207 (pA2
      values: 6.4 and 5.3, respectively). Antagonism by SR 48968 and GR 94800 was
      noncompetitive (both pK8 values 8.9). In summary, NK-2-preferring ligands showed
      superior potency as both binding competitors and contractile agonists,
      demonstrating that NK-2 receptors mediate detrusor muscle contraction, similar to
      the human detrusor. Tachykinins may play important roles in the micturition
      reflex and in regulating detrusor muscle blood flow in the dog.

PMID- 8859023
TI  - Lead (Pb+2) promotes apoptosis in newborn rat cerebellar neurons: pathological
      implications.
AB  - Despite mandated reduction in environmental lead (Pb++), such exposure still
      poses a public health hazard for children, with devastating effects on CNS
      development. To replicate aspects of this neurotoxicity, we used cultured granule
      cells from newborn rat cerebella to study whether apoptotic or necrotic death is
      the major consequence of exposure to low micromolar concentrations of Pb++. At a
      low dose, 1 microM (EC50 approximately equal to 10 microM), Pb++ does not affect
      glutamate-induced neuronal necrosis but promotes neuronal apoptosis, as
      characterized morphologically by cell shrinkage and chromatin condensation,
      biochemically by the typical internucleosomal DNA fragmentation and functionally
      by dependence on new synthesis of macromolecules (cycloheximide- and actinomycin
      D-sensitive). The low micromolar doses of Pb++ that promote apoptosis are well
      within the blood level range reported to impair CNS function in children and to
      alter synaptogenesis in the neonatal rat brain. Thus these in-vitro results
      suggest that the highly neurotoxic action of Pb++ in the developing CNS of
      children might depend on a facilitation of apoptosis. The Pb+2-elicited
      potentiation of neuronal apoptosis is attenuated by treatment with the voltage
      sensitive Ca+2 channel agonist Bay K8644, which suggests the possible use of this
      agonist for treatment of the neurotoxic effects of Pb++.

PMID- 8859024
TI  - Treatment of acyclovir-resistant perianal herpetic ulceration with intramuscular
      interferon alfa.

PMID- 8859025
TI  - Morbilliform eruption in a liver transplantation patient.

PMID- 8859026
TI  - Analysis of 54 cases of hypopigmentation and hyperpigmentation along the lines of
      Blaschko.
AB  - OBJECTIVE: To define the spectrum of disease in cases of hypopigmentation and
      hyperpigmentation along the lines of Blaschko more accurately. Pigmentary
      anomalies along the lines of Blaschko, including hypomelanosis of Ito, linear and
      whorled nevoid hypermelanosis, and nevus depigmentosus, can be associated with
      notable abnormal systemic features. We believe that the incidence of associated
      abnormal features described in previous studies is exaggerated owing to referral
      and reporting bias. DESIGN: Retrospective review of case series. SETTING: An
      ambulatory, university hospital, pediatric dermatology practice and a large, city
      hospital, pediatric dermatology clinic. PATIENTS: Fifty-four children referred
      consecutively over a 5-year period for evaluation of segmental, linear, or
      swirled hypopigmentation and/or hyperpigmentation along the lines of Blaschko.
      MAIN OUTCOME MEASURE: Incidence of associated abnormal systemic features.
      RESULTS: Extracutaneous abnormal features were present in 16 (30%) of 54 children
      with aberrant pigmentation along the lines of Blaschko: in 9 (33%) of 27 with
      hypomelanosis of Ito, in 4 (31%) of 13 with linear and whorled nevoid
      hypermelanosis, in 1 (11%) of 9 with nevus depigmentosus, and in 2 (40%) of 5
      with coexistent hypopigmentation and hyperpigmentation. CONCLUSIONS: Pigmentary
      anomalies along the lines of Blaschko are associated with abnormal systemic
      features far less often than has been reported previously. These pigmentary
      anomalies should not be considered distinct syndromes but rather grouped as a
      heterogeneous collection of disorders indicative of underlying genetic mosaicism.
      Such a classification will allow better understanding and evaluation of affected
      persons.

PMID- 8859027
TI  - Circulating skin-homing T cells in atopic dermatitis. Selective up-regulation of
      HLA-DR, interleukin-2R, and CD30 and decrease after combined UV-A and UV-B
      phototherapy.
AB  - BACKGROUND: As the cutaneous lymphocyte-associated antigen appears to detect
      circulating T cells that migrate to the skin in atopic dermatitis but not T cells
      that migrate to mucosal sites in allergic asthma and rhinitis, we investigated T
      cell activation markers and CD30 on the cutaneous lymphocyte-associated antigen
      positive circulating T-cell subset in atopic dermatitis to see whether these
      markers are different from those in normal controls and related to disease
      activity. DESIGN: Open study. SETTING: University referral center. PATIENTS:
      Twelve patients with atopic dermatitis and 12 healthy controls. INTERVENTION:
      Combined UV-A and UV-B treatment for 2 months. MAIN OUTCOMES MEASURES: Percentage
      of circulating cutaneous lymphocyte-associated antigen-positive T cells that
      express HLA-DR, interleukin-2 receptor, CD69, CD71, and CD30 (triple-color flow
      cytometric analysis). Clinical score, Dermatology Life Quality Index, pruritus
      score, and consumption of topical corticosteroids were determined. RESULTS:
      Increased relative numbers of cutaneous lymphocyte-associated antigen-positive T
      cells expressing HLA-DR, interleukin-2 receptor, and CD30 were found in patients
      with atopic dermatitis before treatment. Treatment with UV-A and UV-B was
      associated with clinical improvement and a decrease of levels of HLA-DR,
      interleukin-2 receptor, and CD30 in cutaneous lymphocyte-associated antigen
      positive T cells. HLA-DR on cutaneous lymphocyte-associated antigen-positive T
      cells correlated significantly with the clinical score. CONCLUSION: Expression of
      HLA-DR and interleukin-2 receptor is a sensitive marker of disease activity in
      atopic dermatitis. Apart from giving information on disease activity in atopic
      dermatitis, the availability of skin-seeking T cells in the blood offers the
      opportunity to obtain further information on T cells that may have effector
      function in the skin.

PMID- 8859028
TI  - Frequency and morphologic characteristics of invasive melanomas lacking specific
      surface microscopic features.
AB  - OBJECTIVES: To create a simple diagnostic method for invasive melanoma with in
      vivo cutaneous surface microscopy (epiluminescence microscopy, dermoscopy,
      dermatoscopy) and to analyze the incidence and characteristics of those invasive
      melanomas that had no diagnostic features by means of hand-held surface
      microscopes. DESIGN: Pigmented skin lesions were photographed in vivo with the
      use of immersion oil. All were excised and reviewed for histological diagnosis. A
      training set of 62 invasive melanomas and 159 atypical nonmelanomas and a test
      set of 45 invasive melanomas and 119 atypical non-melanomas were used. Images
      from the training set were scored for 72 surface microscopic features. Those
      features with a low sensitivity (0%) and high specificity (> 85%) were used to
      create a simple diagnostic model for invasive melanoma. SETTING: All patients
      were recruited from the Sydney (Australia) Melanoma Unit (a primary case and
      referral center). PATIENTS: A random sample of patients whose lesions were
      excised, selected from a larger database. MAIN OUTCOME MEASURES: Sensitivity and
      specificity of the model for diagnosis of invasive melanona. RESULTS: The model
      gave a sensitivity of 92% (98/107) and specificity of 71%. Of the 9 "featureless"
      melanomas the model failed to detect, 6 were pigmented and thin and had a pigment
      network. The other 3 were thicker, hypomelanotic lesions lacking a pigment
      network, some with prominent telangiectases, and all with only small areas of
      pigment. All featureless melanomas noted by the patients had a history of change
      in color, shape, or size. CONCLUSIONS: Surface microscopy does not allow 100%
      sensitivity in diagnosing invasive melanoma and therefore cannot be used as the
      sole indicator for excision. Clinical history is an important consideration when
      featureless lesions are diagnosed.

PMID- 8859029
TI  - Nodular basal cell carcinoma in vivo vs in vitro. Establishment of pure cell
      cultures, cytomorphologic characteristics, ultrastructure, immunophenotype,
      biosynthetic activities, and generation of antisera.
AB  - BACKGROUND AND DESIGN: In this study we developed an in vitro model of nodular
      basal cell carcinoma (BCC). We obtained pure cultures of BCC cells and compared
      the morphologic characteristics, ultrastructure, immunophenotype, and behavior of
      cultured tumor cells with those of their in vivo counterparts. Tumors were
      excised from patients undergoing Mohs micrographic surgery. We established 69
      primary cell cultures from 32 patients with nodular BCC. RESULTS: Three cell
      types grew in primary cultures: fibroblasts, normal-appearing keratinocytes, and
      cells with dual (spindle and epithelioid) morphologic characteristics.
      Contaminating fibroblasts were removed using 0.125% trypsin-0.02% edetic acid,
      and normal-appearing keratinocytes were cornified and eliminated by temporarily
      increasing the concentration of calcium in the growth medium. The cells with dual
      morphologic characteristics remained intact and exhibited relentless growth in
      pure cultures. That these seemingly immortal cell strains represent true nodular
      BCC was demonstrated by (1) their biphasic morphologic characteristics and very
      slow cell growth rate, (2) their capability for anchorage-independent growth in
      soft agar, (3) their ultrastructural similarities to freshly excised nodular BCC,
      (4) their ability to generate antibodies selectively labeling nodular BCC tumor
      nests in vivo, and (5) their immunophenotypic similarities to BCC in vivo on more
      than 20 different cell markers. CONCLUSIONS: This study provides a simple
      technique for establishing pure cell cultures of nodular BCC and describes
      extensively the in vitro parameters of tumor cell growth. The striking
      differences in behavior of cultured tumor cells in the presence or absence of
      normal-appearing keratinocytes suggest that normal human epidermal keratinocytes
      can suppress the growth of BCC cells.

PMID- 8859030
TI  - Immune-mediated subepithelial blistering diseases of the mucous membranes.
      Improving the detection of circulating autoantibodies by the use of concentrated
      serum samples.
AB  - BACKGROUND AND DESIGN: Comparison of detection of circulating autoantibodies
      before and after concentration of serum samples from patients with suspected
      immune-mediated subepithelial blistering diseases of the mucous membranes. We
      determine whether the use of concentrated serum samples from patients with
      suspected immune-mediated subepithelial blistering diseases of the mucous
      membranes improves diagnostic sensitivity for circulating antibodies. We studied
      13 patients from a university-based referral practice who had no skin lesions and
      a scarring subepithelial blistering disease of the mucous membranes. Three of
      these patients had detectable circulating autoantibodies and 10 had negative
      indirect immunofluorescence study results using standard techniques. The main
      outcome measures after concentration of serum samples were detection of
      circulating autoantibodies on salt-split skin by indirect immunofluorescence,
      immunoblotting, and immunoprecipitation. RESULTS: Of the 10 patients in whom
      circulating autoantibodies had not been detectable with standard techniques,
      circulating IgG antibodies were detected in 5 (50%) and circulating IgA
      antibodies in 3 (30%). Of the 3 patients in whom circulating autoantibodies had
      been detectable with standard techniques, 1 (33%) had circulating IgA antibodies
      that immunoblotted the 97-kd linear IgA bullous disease antigen only when
      concentrated serum samples were used. CONCLUSIONS: The use of concentrated serum
      samples can improve our ability to detect the presence and antigenic specificity
      of circulating autoantibodies in patients with suspected but unclassifiable
      immune-mediated subepithelial blistering diseases of the mucous membranes.

PMID- 8859031
TI  - Serum from normal elderly individuals contains anti-basement membrane zone
      antibodies.
AB  - BACKGROUND: Bullous pemphigoid is an autoimmune bullous disease with circulating
      anti-basement membrane zone antibodies, and it commonly affects elderly
      individuals; however, the reasons for the late onset of the disease are unclear.
      DESIGN: The anti-basement membrane zone antibodies in serum samples from normal
      elderly subjects were compared with those in serum samples from normal young
      subjects. PARTICIPANTS: Serum samples from 32 elderly and 28 young normal
      individuals and 10 patients with bullous pemphigoid were used. INTERVENTIONS:
      Indirect immunofluorescence against guinea pig esophagus or human salt-split
      epidermis and immunoblotting against human and guinea pig epidermis were
      performed. RESULTS: Serum samples from young individuals were devoid of anti
      basement membrane zone antibodies against guinea pig esophagus and human salt
      split epidermis. Among 32 serum samples from elderly patients, 6 cases (19%) were
      positive for anti-basement membrane zone antibody for guinea pig esophagus, and
      in those the titers were 10 in 3 cases and 40, 80, and 320 in the others. One
      case was positive against human split epidermis at a titer of 10. An
      immunoblotting analysis showed that the antigenicity of the 230-kd and 180-kd
      bullous pemphigoid antigen from guinea pig epidermal extract was similar to that
      of human epidermal extract; however, the molecular weight was slightly different.
      The 4 cases of elderly serum that recognized guinea pig esophagus basement
      membrane zone showed positivity with the 230-kd peptide in the guinea pig
      epidermal extract; however, they were negative with the human epidermal extracts.
      Direct immunofluorescence observation of these cases showed that deposition of
      IgG or C3 was not present in cryostat sections from flexor arm surfaces.
      CONCLUSIONS: The serum samples from elderly subjects possessed a relatively high
      incidence of anti-basement membrane zone antibodies detectable with guinea pig
      esophagus as substrate. This observation of a specific immune defect in elderly
      individuals might explain why they are more susceptible to developing bullous
      pemphigoid.

PMID- 8859032
TI  - Keratinocytes as a target for gene therapy. Sustained production of
      erythropoietin in mice by human keratinocytes transduced with an adenoassociated
      virus vector.
AB  - BACKGROUND AND DESIGN: Keratinocytes are ideal targets for somatic gene therapy.
      Among the viral gene transfer systems, adenoassociated virus vectors have
      recently gained attention. We studied the feasibility of using adenoassociated
      virus-transduced human keratinocytes to provide a long-term, high-level
      production of a therapeutic factor after implantation in mice. RESULTS:
      Transduction of HeLa cells by an adenoassociated virus vector was ascertained by
      transfer of the beta-galactosidase reporter gene, which was visualized by the
      blue staining of infected cells after fixation and coloring by X-Gal (the
      substrate of the reaction for beta-galactosidase activity). In a second step, 2
      HeLa cell lines transduced with an AAV harboring the erythropoietin complementary
      DNA and producing high amounts of erythropoietin in vitro were isolated. After
      implantation in nude mice, a high-level and long-term increase in hematocrit (for
      the 1-month duration of the study) was found, which was correlated to the size of
      the induced tumor. CONCLUSIONS: Adenoassociated virus-transduced HeLa
      keratinocytes provide high-level, stable, and long-term production of a
      therapeutic protein in mice. These results must now be extended to human primary
      keratinocytes.

PMID- 8859033
TI  - Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome.
AB  - BACKGROUND: The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to
      reflect the clinical overlap of 3 conditions previously described as separate
      entities, each inherited in an autosomal dominant fashion. They are the Riley
      Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. OBSERVATIONS: We
      studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic
      cutaneous findings included multiple subcutaneous lipomas and vascular
      malformations, lentigines of the penis and vulva, verrucae, and acanthosis
      nigricans. Macrocephaly with normal ventricular size, mental retardation, central
      nervous system vascular malformations, intestinal polyposis, skeletal
      abnormalities, and thyroid tumors were the most common systemic featues. A
      striking clinical finding in 1 patient was widespread verrucous changes of both
      lips that histologically showed epidermal hyperplasia with papillomatosis and
      hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological
      features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the
      epidermis with increased pigment in the basal layer and a slight increase in the
      number of melanocytes were seen in biopsy specimens of the penile lentigines.
      CONCLUSIONS: The histologic findings of both the facial lesions and the pigmented
      macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our
      knowledge, been reported previously. The similarities between the Bannayan-Riley
      Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic
      pathogenesis for these 2 diseases.

PMID- 8859034
TI  - Angiokeratoma corporis diffusum associated with beta-mannosidase deficiency.
AB  - BACKGROUND: Angiokeratoma corporis diffusum (ACD) was at one time thought to be
      synonymous with Anderson-Fabry disease. However, it is well known that widespread
      angiokeratomas may also be found in other lysosomal enzyme disorders, as well as
      in patients with normal enzyme activities. beta-Mannosidase deficiency was first
      described in humans in 1986; since then, only 11 cases of beta-mannosidase
      deficiency, which occurred in 8 families, have been reported. Although the
      clinical manifestations are varied, mental retardation and neurologic disorders
      are present in practically all patients. OBSERVATIONS: We describe a 22-year-old
      woman who, since the age of 12 years, presented with progressive ACD affecting
      the lower limbs and the buttocks. Enzymatic studies revealed beta-mannosidase
      deficiency in cultured fibroblasts and in samples of serum and leukocytes. The
      patients's parents in turn exhibited intermediate enzyme levels, thus confirming
      the recessive autosomal hereditary nature of the disease. With the exception of
      an introverted character, the patient demonstrated no other anomalies.
      CONCLUSIONS: This is the first case of beta-mannosidase deficiency diagnosed as a
      result of purely dermatologic findings, in the form of ACD. beta-Mannosidase
      deficiency should therefore be included when screening for enzyme abnormalities
      in patients with ACD, even in the absence of neurologic disorders or mental
      retardation.

PMID- 8859035
TI  - Treatment of traumatic tattoos with the Q-switched neodymium:YAG laser.
AB  - BACKGROUND: Treatment for traumatic tattoos often results in incomplete removal
      of the pigment or produces unacceptable scars or textural changes. Successful
      results using Q-switched ruby lasers have been reported. The Q-switched
      neodymium:YAG laser, with a wavelength of 1064 nm and a pulse duration of 5 to 7
      nanoseconds, penetrates deeper into the skin and has less interaction with
      melanin than the Q-switched ruby laser. OBSERVATIONS: The present study documents
      32 cases of traumatic tattoos involving 51 sites of the face, trunk, and
      extremities in patients ranging in age from 6 to 58 years. All patients were
      treated with the Q-switched neodymium:YAG laser. Excellent results were noted for
      50 of 51 treated tattoos. The number of treatments to achieve excellent results
      ranged from 1 to 6, with an average of 1.7. No scarring, atrophy, textural
      changes, or hypopigmentation was noted in any of the cases. Transient
      postinflammatory hyperpigmentation of 3 months' duration was noted in 1 patient.
      CONCLUSION: The Q-switched neodymium:YAG laser was effective in removing
      traumatic tattoos without any significant side effects.

PMID- 8859036
TI  - Assembling the puzzle pieces in atopic inflammation.

PMID- 8859037
TI  - Pigmentary patterning as a clinical clue of genetic mosaicism.

PMID- 8859038
TI  - Scaly erythematous lesion in a patient with extensive solar damage. Malignant
      melanoma in situ, amelanotic type.

PMID- 8859039
TI  - A distinctive annular facial plaque. Desmoplastic trichopithelioma.

PMID- 8859040
TI  - An edentulous woman with warty lesions. Lipoid proteinosis.

PMID- 8859041
TI  - Hepatitis C virus in dermatology.

PMID- 8859042
TI  - Fatal flaw of Stanton's doomsday Rx.

PMID- 8859043
TI  - Idiopathic CD4+ T lymphocytopenia presenting as mycetoma in a patient with a
      mutation in the cystic fibrosis transmembrane regulator gene.

PMID- 8859044
TI  - Treatment of psoriasis by cyclosporine and grapefruit juice.

PMID- 8859045
TI  - Treatment of minocycline-induced hyperpigmentation with the Q-switched ruby
      laser.

PMID- 8859046
TI  - Q-switched ruby laser treatment of minocycline-induced cutaneous
      hyperpigmentation.

PMID- 8859047
TI  - Acute generalized exanthematous pustulosis induced by terbinafine.

PMID- 8859048
TI  - Coadministration of itraconazole with hypolipidemic agents may induce
      rhabdomyolysis in healthy individuals.

PMID- 8859049
TI  - Rhabdomyolysis associated with azathioprine hypersensitivity syndrome.

PMID- 8859050
TI  - Sisaipho: a new form of presentation of alopecia areata.

PMID- 8859051
TI  - Delayed-type hypersensitivity after subcutaneous administration of amide
      anesthetic.

PMID- 8859052
TI  - Demonstration of human papillomavirus type 16-related DNA and absence of
      detectable p53 gene mutations in widespread cutaneous squamous cell carcinomas
      after oral psoralen with UV-A treatment.

PMID- 8859053
TI  - Pseudocervical cord syndrome: a deceptive flumazenil reversible manifestation of
      hepatic encephalopathy.

PMID- 8859054
TI  - A pilot study of pentoxifylline in multiple sclerosis.

PMID- 8859055
TI  - Cerebral infarct after rattlesnake bite.

PMID- 8859056
TI  - Posterior cortical atrophy: neuropathological correlations.

PMID- 8859057
TI  - Cavernous sinus syndrome. Analysis of 151 cases.
AB  - OBJECTIVE: To characterize lesions causing cavernous sinus syndrome. DESIGN:
      Review of 26 years of personal experience in a large city hospital. RESULTS:
      Among 151 patients, tumors (45 patients, 30%) were the most frequent cause of
      cavernous sinus syndrome. However, when surgical causes (17 patients, 11%) were
      included, trauma (36 patients, 24%) became most common. Self-limited inflammation
      was the third frequent cause (34 patients, 23%), while carotid aneurysms and
      fistulas, infection, and other causes composed the remaining 12%. The age at
      onset varied with the cause, and patients with aneurysms (average age, 52 years)
      and patients with tumors (average age, 47 years) were older than those with self
      limited inflammation (average age, 35 years) and trauma (average age, 29 years).
      Spontaneous remissions defined "self-limited inflammation" but were also seen
      following an acute onset of symptoms due to aneurysms and pituitary apoplexy.
      CONCLUSIONS: In an unselected series from a city hospital, tumor, trauma, and
      self-limited inflammation were the predominant causes of cavernous sinus
      syndrome, and classic causes such as aneurysm, meningioma, and bacterial
      infection were uncommon. Contrast-enhanced magnetic resonance imaging and
      watchful waiting proved the most effective diagnostic procedures.

PMID- 8859058
TI  - Amnesia in acute herpetic and nonherpetic encephalitis.
AB  - OBJECTIVES: To evaluate how often global amnesia syndrome is encountered as a
      sequel of herpes simplex virus type 1 encephalitis (HSVE) and in other types of
      acute encephalitides, and to evaluate whether there are qualitative differences
      in amnesia caused by different encephalitides. SUBJECTS: Forty-five consecutive
      patients with encephalitis (mean age, 40.8 years) studied prospectively within a
      5-year period, 8 of whom had HSVE. There were 24 normal controls. MEASURES:
      Neuropsychological assessment and memory evaluation after the acute stage of
      encephalitis, as well as at follow-up after 27.7 +/- 18.6 months. RESULTS: Three
      patients (6%), including 1 with HSVE, had persistent anterc grade and retrograde
      memory defects, typical features of global amnesia. Twelve patients had
      anterograde amnesia in the first assessment. No statistically significant
      differences in the memory measures were found between the HSVE (n = 4) and the
      non-HSVE (n = 8) groups. Some patients had predominantly semantic difficulty,
      some had a "frontal-type" memory disorder, and in some patients rapid forgetting
      was the prominent feature. CONCLUSIONS: The frequency of amnesia can reliably be
      evaluated only in consecutive series of patients. Previous literature, mainly
      case reports, may give the impression that global amnesia is a common consequence
      of encephalitis. Our findings do not support that view. Furthermore, there are
      clear differences in the quality of the memory impairment between cases of acute
      encephalitides. Our findings suggest that amnesia as a consequence of
      encephalitis, even HSVE, should not be considered a uniform phenomenon.

PMID- 8859059
TI  - Screening for cognitive dysfunction in multiple sclerosis.
AB  - BACKGROUND: With the use of comprehensive neuro-psychological assessments, a
      substantial proportion of patients with multiple sclerosis have been found to
      have substantial cognitive impairment. Although data generated from comprehensive
      examinations are useful in making recommendations for treatment interventions and
      compensatory strategies, the cost of such assessments prohibits their use with
      all patients. OBJECTIVE: To develop a screening battery to detect cognitive
      impairment in patients with multiple sclerosis that is sensitive, specific,
      brief, and cost-effective, and could identify patients who might benefit from a
      more comprehensive neuropsychological examination. DESIGN: On the basis of a
      comprehensive neuropsychological assessment battery, the presence of significant
      cognitive impairment was determined in patients with multiple sclerosis. The
      screening battery consisted of a subset of tests from the comprehensive battery.
      Performance on the screening battery was then used to predict presence of
      cognitive impairment on the comprehensive battery in validation and cross
      validation samples. Severity of impairment on the screening battery was also
      regressed on ratings of functional impairment derived from the Expanded
      Disability Status Scale. RESULTS: In the validation sample, the screening battery
      had 100% sensitivity, 80% specificity, and 88.1% overall diagnostic accuracy. In
      the cross-validation sample, the screening battery had 100% sensitivity, 81.8%
      specificity, and an overall diagnostic accuracy rate of 90.7%. chi 2 tests showed
      that the accuracy of the screening battery was significantly better than chance
      in both samples. Performance on the screening battery also predicted the level of
      disability ratings on the Expanded Disability Status Scale and functional systems
      scales. CONCLUSIONS: The screening battery had a high degree of sensitivity,
      specificity, and diagnostic accuracy, while maintaining a brief administration
      time and high cost-effectiveness. The screening battery also predicted higher
      levels of disability and functional impairment as assessed by the Expanded
      Disability Status Scale, thereby enhancing its clinical utility. Despite its
      advantages, the findings do not suggest that the screening battery may be an
      effective substitute for a more detailed examination.

PMID- 8859060
TI  - Motor neuron disease with parkinsonism.
AB  - OBJECTIVE: To report clinical characteristics of patients with combined features
      of parkinsonism and motor neuron disease (MND). DESIGN: Medical chart review.
      SETTING: University medical center. PATIENTS: Thirteen patients, identified by
      computer-assisted search, who had diagnoses of both parkinsonism and MND.
      RESULTS: Median age was 68 years. There were 7 men and 6 women. All had clinical
      and electrodiagnostic evidence of both upper and lower motor neuron degeneration.
      One or more clinical manifestations of parkinsonism were observed in all patients
      either before the diagnosis of MND (n = 2), at the time of initial evaluation (n
      = 10), or after the diagnosis of MND (n = 1). The median time from symptom onset
      to presentation was 18 months. Improvement was seen in 5 of the 11 patients
      treated with levodopa. Dementia and autonomic dysfunction were absent in all
      patients. Postmortem neuropathological evaluation, available in 1 patient,
      demonstrated degeneration of the substantia nigra with Lewy bodies, mild pallor
      of the medullary pyramids, and neurogenic atrophy of the skeletal muscle.
      CONCLUSION: The onset of MND and parkinsonism within a relatively short period in
      most of our patients favors a common pathogenic mechanism over coincidental
      occurrence of 2 unrelated diseases. In patients with MND, it is important to
      recognize signs of parkinsonism that levodopa might alleviate.

PMID- 8859061
TI  - Excess glutamate levels in the cerebrospinal fluid predict clinical outcome of
      bacterial meningitis.
AB  - BACKGROUND: The clinical course of bacterial meningitis still is characterized by
      a high mortality and frequent neurological deficits in survivors. In addition to
      other potentially neurotoxic mediators of inflammation, the excitatory amino acid
      glutamate, which has been implicated in neuronal death in a variety of other
      neurological diseases, may also be involved in the pathological process of
      bacterial meningitis. OBJECTIVES: To investigate the prognostic value of the
      glutamate concentration in the cerebrospinal fluid (CSF) of patients with
      bacterial meningitis. PATIENTS AND METHODS: Thirty consecutive patients with
      bacterial meningitis were included in a prospective study. The clinical severity
      of the disease was assessed on admission and 14 days after the beginning of
      antibiotic treatment by means of the Glasgow Coma Scale. Studies of CSF were
      performed on admission and after 3 to 6 days. In addition to standard CSF
      investigations, including cell count, cytologic findings, protein analysis,
      glucose and lactate levels, and microbiological tests, the concentration of
      glutamate in the CSF was measured by an enzymatic assay. RESULTS: At admission,
      both CSF cell count and concentration of glutamate correlated well with the
      severity of the disease. After treatment, glutamate concentrations decreased
      significantly to normal or only slightly elevated levels in 23 patients. However,
      in 7 patients glutamate levels remained markedly increased. In this group,
      clinical outcome was significantly worse than in the group of patients with low
      glutamate levels in the second CSF analysis. CONCLUSIONS: A prolonged increase of
      glutamate levels in the CSF may predict poor clinical outcome in patients with
      bacterial meningitis, possibly because of the sustained neurotoxic effects of
      this excitatory neurotransmitter.

PMID- 8859062
TI  - Genetic factors for the development of Alzheimer disease in the Cherokee Indian.
AB  - OBJECTIVE: To study the relationship between the genetic degree of Cherokee
      ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of
      Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in
      northeastern Oklahoma. SETTING: Alzheimer disease center satellite clinic and
      university departments of neurology, psychiatry, and academic computing. DESIGN:
      Standardized dementia evaluations based on criteria from the National Institute
      of Neurological and Communicative Disorders and Stroke and the Alzheimer's
      Disease and Related Disorders Association were performed on 26 patients aged 65
      years or older to establish a diagnosis of AD. Twenty-six control subjects were
      recruited and similarly assessed. The APOE allele type determinations were
      obtained on all patients and control subjects. Appropriate statistical analyses
      were used to compare the genetic degree of Cherokee ancestry, the APOE allele
      type, and the development of AD. RESULTS: The data indicated that as the genetic
      degree of Cherokee Indian ancestry increased, the representation of AD decreased.
      The 9 patients with AD with a greater than 50% genetic degree of Cherokee
      ancestry constituted 35% of the group with AD. The 17 remaining patients with AD
      who were less than 50% Cherokee constituted 65% of the group with AD. In
      contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9
      (35%) were less than 50% Cherokee. These percentages of AD were not changed by
      the *E4 allele. This inverse relationship between the genetic degree of Cherokee
      ancestry and AD, independent of the APOE*E4 allele status, diminished with
      increasing age, suggesting an age-related protective effect of being Cherokee.
      For a decrease of 10% in Cherokee ancestry, the odds of developing AD are
      estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at
      age 80 years. CONCLUSIONS: A greater genetic degree of Cherokee ancestry reduces
      the risk of developing AD and, thus, seems protective. This protective genetic
      factor is independent of APOE allele type and diminishes with age.

PMID- 8859063
TI  - Effect of valproate on cognitive functioning. Comparison with carbamazepine. The
      Department of Veterans Affairs Epilepsy Cooperative Study 264 Group.
AB  - OBJECTIVE: To assess the effects of carbamazepine vs valproate sodium on
      cognitive functioning in patients with epilepsy compared with normal control
      subjects. DESIGN: Patients with recently diagnosed, previously unmedicated
      seizures participated in a prospective randomized double-blind Department of
      Veterans Affairs multicenter study of the efficacy and toxicity of carbamazepine
      vs valproate. MAIN OUTCOME MEASURE: A behavioral toxicity battery was
      administered prior to treatment and again 6 and 12 months after the initiation of
      antiepileptic medication. RESULTS: There were no significant differences in the
      effect of carbamazepine vs valproate on motor speed and coordination, memory, or
      concentration and mental flexibility, and there was no significant decline in
      neuropsychological performance from pretreatment baseline levels for either drug.
      No significant differences in performance were found between patients with low
      (mean, 52.8 micrograms/mL) vs high (mean, 94.4 micrograms/mL) serum valproate
      levels within the therapeutic range. Patients treated with either carbamazepine
      or valproate did not show practice effects experienced by normal controls, a
      finding that may reflect a subtle compromise in cognitive functioning.
      CONCLUSION: The impact of carbamazepine and valproate monotherapy on cognitive
      functioning is similar: both drugs produce minimal negative effects compared with
      pretreatment baseline performance.

PMID- 8859064
TI  - Treatment of Wilson disease with ammonium tetrathiomolybdate. II. Initial therapy
      in 33 neurologically affected patients and follow-up with zinc therapy.
AB  - OBJECTIVE: To test the efficacy and toxic effects of ammonium tetrathiomolybdate
      in the initial treatment of a relatively large series of patients with neurologic
      symptoms and signs caused by Wilson disease. Two key aspects of efficacy are to
      preserve the neurologic function present at the onset of therapy and to maximize
      the opportunity for long-term recovery. DESIGN: An open study of 33 patients
      treated for 8 weeks each, including further follow-up data on the original 17
      patients. Neurologic function was evaluated by frequent quantitative neurologic
      and speech pathology examinations. Several copper-related variables were studied
      to evaluate the effect of the drug on copper, and several biochemical and
      clinical variables were studied to evaluate potential toxic effects. Patients
      were then followed up at yearly intervals, with follow-up periods of 1 to 8 years
      reported. SETTING: A university hospital referral setting. INTERVENTION: Patients
      were generally treated for 8 weeks with tetrathiomolybdate, followed by zinc
      maintenance therapy. MAIN OUTCOME MEASURES: Neurologic function was evaluated by
      quantitative neurologic and motor speech examinations and magnetic resonance
      imaging scans of the brain. RESULTS: During the 8 weeks of tetrathiomolybdate
      administration, only 1 of the 33 patients showed deterioration in neurologic
      function. Copper status and potential further toxic effects were generally well
      controlled quickly. Evaluation of data from individual patients revealed evidence
      of a toxic side effect in only 1 patient, who exhibited reversible anemia. During
      the ensuing period of follow-up of 1 to 6 years, neurologic recovery in most
      patients was good to excellent. CONCLUSIONS: Tetrathiomolybdate appears to be an
      excellent form of initial treatment in patients with Wilson disease who present
      with neurologic symptoms and signs. In contrast to penicillamine therapy, initial
      treatment with tetrathiomolybdate rarely allows further, often irreversible,
      neurologic deterioration.

PMID- 8859065
TI  - Crossed aphasia. Functional brain imaging with PET or SPECT.
AB  - OBJECTIVES: To study patients with crossed aphasia (aphasia secondary to lesions
      in the right hemisphere in right-handed patients) with functional brain imaging
      using positron emission tomography (PET) or single photon emission computed
      tomography (SPECT); to see whether left hemisphere structures were metabolically
      depressed during the acute phase and, in 1 patient, during recovery; and to
      review the modern literature on crossed aphasia, with special reference to left
      hemisphere involvement. DESIGN: Case studies of 3 patients with crossed aphasia,
      including language testing, computed tomographic scanning, and functional imaging
      with PET or SPECT. SETTING: Hospital case studies. PATIENTS: Three right-handed
      patients with crossed aphasia secondary to acute infarctions in the right
      hemisphere and left hemiparesis. METHODS: All 3 patients were studied by means of
      bedside language testing, computed tomographic scanning, and functional brain
      imaging with PET or SPECT. Patient 1 also underwent serial testing with the
      Boston Diagnostic Aphasia Examination and follow-up PET scanning after 2 months
      of recovery. OUTCOME MEASURES: Clinical examination in all 3 patients and follow
      up Boston Diagnostic Aphasia Examination and PET scanning in patient 1. RESULTS:
      Two patients had severe global aphasia and 1 had Broca aphasia. In all cases,
      computed tomographic scans failed to reveal any left hemispheric lesions.
      Functional imaging with PET or SPECT showed extensive hypometabolism or
      hypoperfusion in the right hemisphere, with initial reductions in the left
      hemisphere as well. In patient I, a follow-up PET image showed only persistent
      hypometabolism in the right hemisphere. CONCLUSIONS: These findings suggest that
      abnormal dominance for at least some language functions in the right hemisphere
      underlies the syndrome of crossed aphasia. Diaschisis, or functional depression
      of the anatomically normal left hemisphere, was seen in all 3 patients during the
      acute phase, but not in patient 1 after recovery had begun.

PMID- 8859066
TI  - Do long tests yield a more accurate diagnosis of dementia than short tests? A
      comparison of 5 neuropsychological tests.
AB  - OBJECTIVE: To provide comparative evidence for a valid and practical measure of
      mental-status functioning that could be used in dementia clinics. DESIGN: Five
      mental-status neuropsychological tools for dementia screening were administered
      to patients in a memory disorder clinic. These included the Mini-Mental State
      Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation
      Memory-Concentration Test, a short Mental Status Questionnaire, and a composite
      tool we labeled the Ottawa Mental Status Examination, which assessed orientation,
      memory, attention, language, and visual-constructive functioning. The tools were
      compared using various criteria, including the statistical factors of sensitivity
      and reliability; effects of gender, native language, and language of testing; the
      utility of these tests for the differential diagnosis of Alzheimer-type and
      vascular dementia; and sensitivity to cognitive decline in the entire sample and
      among patients with severe dementia. RESULTS: All of the tests were highly
      intercorrelated, suggesting that they are interchangeable. CONCLUSION: The
      comparisons along the various criteria indicate that if the objective is to have
      a general index of dementia of the Alzheimer type, short tests are at least as
      good and sometimes better than the longer tests.

PMID- 8859067
TI  - Diagnosis of dementia. Methods for interpretation of scores of 5
      neuropsychological tests.
AB  - OBJECTIVE: To provide methods to interpret and compare different neurobehavioral
      screening tests for the diagnosis of dementia. DESIGN: Five mental-status
      neuropsychological tools for dementia screening were administered to patients in
      a memory disorder clinic. These included the Mini-Mental State Examination, the
      Dementia Rating Scale, the 6-item derivative of the Orientation-memory
      Concentration Test, a short Mental Status Questionnaire, and a composite tool we
      labeled the Ottawa Mental Status Examination, which assessed orientation, memory,
      attention, language, and visual-constructive functioning. RESULTS: To obtain z
      and percentile scores, norms are for the different tests, computed separately for
      patients with dementia of the Alzheimer type, vascular dementia, or no dementia.
      Another set of norms is reported in which a test score is translated directly
      into the posttest probability of dementia. Translation formulas are given to
      allow the estimation of the score on one test from the result on another test.
      CONCLUSION: The interpretation of tests used to diagnose dementia must be based
      on an understanding of the meaning of an individual score, which is based on the
      question asked and the population to which the patient is referenced.

PMID- 8859068
TI  - Age at onset and pattern of neuropsychological impairment in mild early-stage
      Alzheimer disease. A study of a community-based population.
AB  - OBJECTIVES: To examine the effects of age at onset on neuropsychological
      functioning in a group of patients with probable Alzheimer disease (AD) and,
      within this group, to scrutinize further those patients with mild early-onset
      disease as it was hypothesized that within this group specific patterns of
      cognitive impairment could be identified that correlated with neuropathological
      staging of the disease. DESIGN: Each patient underwent an extensive
      neuropsychological test battery to examine a wide range of cognitive processes to
      provide information to identify subtypes of dementia. SETTING: The Memory Clinic
      in the Department of Geriatric Medicine, Concord Hospital, Concord, New South
      Wales, Australia. PATIENTS: One hundred forty-five community-residing case
      patients with probable AD were studied; within this group, 51 case patients with
      mild AD and a Mini-Mental State Examination score greater than 19 were further
      examined; 36 similarly aged control patients who were part of a larger case
      control study of AD in an urban population were also examined. A diagnosis of
      probable and possible AD was made if the case patient had evidence of memory
      impairment and met criteria according to the National Institute of Neurological
      and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association. OUTCOME MEASURES: Individual neuropsychological test scores were
      compared. The tests were then grouped into 7 cognitive domains. Patterns of early
      cognitive impairment were derived from these comparisons. RESULTS: With an
      earlier age at onset, significantly more impairment on tests of digit span and
      praxis was seen, while the duration of disease had no independent effect once the
      age at onset was fixed. Patients with mild early-onset dementia and a Mini-Mental
      State Examination score greater than 19 showed significant impairment in tests of
      attention, memory, frontal/executive functions, visuospatial ability, praxis, and
      visual agnosia compared with that shown by control patients. In this group,
      further analyses revealed that impairment in memory and frontal/ executive
      functions were the earliest signs of cognitive impairment. CONCLUSIONS: These
      data showed that when the duration of disease was adjusted for, case patients
      with an earlier age at onset of AD demonstrated significantly more impairment on
      tests of attention span and working memory (digit span), graphomotor function
      (copy loops), and apraxia than those with an older age at onset. Our findings
      support the view that the hippocampus and its connections are affected in the
      early stages of AD. The deficits in the frontal/executive functions also suggest
      that a disruption of cortical pathways to the frontal lobes and the pathological
      changes in this region occur early in the disease.

PMID- 8859069
TI  - The validity of rodent brain-ischemia models is self-evident.

PMID- 8859070
TI  - Rodent models of stroke limitations. What can we learn from recent clinical
      trials of thrombolysis?

PMID- 8859072
TI  - Alzheimer disease and nonfluent progressive aphasia.
AB  - OBJECTIVE: To describe a patient with pathologically proven Alzheimer disease
      (AD) who presented with a non-fluent progressive aphasic syndrome. DESIGN:
      Longitudinal neuropsychological assessment, structural (magnetic resonance
      imaging) and functional (single photon emission computed tomography) imaging, and
      postmortem brain examination. SETTING: Memory and cognitive disorders clinic in a
      tertiary referral hospital. PATIENT: A 66-year-old man presented with a 5-year
      history of progressive nonfluent aphasia characterized by marked deficits in
      phonology and syntax with preservation of everyday abilities. His condition
      deteriorated rapidly and he died suddenly of a myocardial infarction 12 months
      later. RESULTS: Neuropsychological testing revealed mild global intellectual
      impairment with marked impairment of auditory verbal short-term memory,
      syntactic, and phonological abilities. His naming errors were predominantly
      phonological paraphasias. Magnetic resonance imaging scans showed left
      perisylvian atrophy and results of a Tc 99m hexamethyl-propyleneamine-oxime
      single photon emission computed tomographic scan were normal. Postmortem
      pathological examination revealed typical AD pathological features with atypical
      distribution, involving predominantly perisylvian language areas, but sparing the
      medial temporal lobe. CONCLUSIONS: The language deficits in AD, which have
      received considerable attention, are thought to involve predominantly
      lexicosemantic processes. When AD presents as a relatively isolated language
      disturbance, the aphasia is usually of the fluent anomic type. To our knowledge,
      our patient represents the first fully documented case of progressive nonfluent
      aphasia with pathologically verified AD.

PMID- 8859073
TI  - Discrete nuclear sclerosis in young patients with myopia.
AB  - OBJECTIVE: To review a series of young patients with myopia who had a visually
      disabling cataract. DESIGN: A retrospective review of 12 consecutive patients who
      had a visually disabling cataract and who were examined at the Cornea Service of
      the University of Illinois at Chicago. RESULTS: The mean age of the patients was
      44 years (range, 34-54 years). The mean best-corrected visual acuity of the
      patients was 20/50, and the ocular history of the patients included a progressive
      decrease in vision. Six patients experienced disabling monocular polyopia. Their
      presumed diagnoses ranged from keratoconus to myopic degeneration. All of the
      patients noted resolution of their symptoms after cataract extraction.
      CONCLUSIONS: These patients are a select group that tends not to follow the
      established associations between visually significant lens opacities, age, and
      myopia. Cataract extraction is therapeutic, and prompt diagnosis can obviate
      unnecessary testing and repeated office visits.

PMID- 8859074
TI  - Uveitis associated with topical beta-blockers.
AB  - OBJECTIVE: To assess the incidence of uveitis associated with topical beta
      blockers. DESIGN: Retrospective cohort study. SETTING: A computerized database of
      a health maintenance organization was used to identify patients who were
      prescribed metipranolol or other beta-blockers. PATIENTS: Two groups: 1928
      patients using 0.3% metipranolol and 3903 patients using other beta-blockers.
      MAIN OUTCOME MEASURE: Cases of uveitis were identified by noting a prescription
      of a topical corticosteroid and then conducting a chart review. RESULTS: No cases
      of uveitis were identified among the 5831 patients. The upper limits of the 95%
      confidence intervals for the incidence of uveitis in cohorts of this size are
      1.87 cases per 1000 person-years of exposure for metipranolol and 1.38 for other
      beta-blockers. CONCLUSION: Drug-induced uveitis from metipranolol or other beta
      blocker administration is a rare event, even if a causal relationship exists.

PMID- 8859075
TI  - Melanin-laden macrophages in cerebrospinal fluid in Vogt-Koyanagi-Harada
      syndrome.
AB  - OBJECTIVE: To identify basophilic granules in the cytoplasm of macrophages in
      cerebrospinal fluid (CSF) smears from patients with Vogt-Koyanagi-Harada (VKH)
      syndrome as melanin pigment. DESIGN: Morphological and immunocytochemical studies
      were performed on CSF smears obtained from 7 patients with VKH syndrome.
      Specimens were stained with May-Grunwald and evaluated by a silver impregnation
      method (Fontana-Masson staining). For immunocyto-chemical study, the smear was
      reacted with mouse anti-human melanoma cell (HMB-45) monoclonal antibody.
      RESULTS: Basophilic granules were detected in the cytoplasm of macrophages in CSF
      cell smears obtained from 6 of 7 patients with VKH syndrome in the early stages
      (within 25 days). Using the silver impregnation method, these basophilic granules
      were strongly stained black. Moreover, they were identified as melanin by
      positive immunocytochemical staining. The total number of cells containing
      cytoplasmic granules ranged from 3 to 8 per 10,000 total cells in CSF. In
      contrast, no cells containing cytoplasmic granules were found in control CSF cell
      smears from patients with viral, bacterial, or noninflammatory diseases.
      CONCLUSION: The identification of melanin-laden macrophages in the CSF of
      patients with VKH syndrome suggests that these cells are responsible for
      pleocytosis in the immunopathologic process of VKH syndrome.

PMID- 8859076
TI  - Transthoracic echocardiographic findings in patients with acute retinal arterial
      obstruction. A retrospective review. Retinal Emboli of Cardiac Origin Group.
AB  - OBJECTIVE: To assess the importance of cardio-embolic (emboli of cardiac origin)
      risk stratification in the cardiac evaluation of patients with acute retinal
      arterial obstruction. DESIGN: A multicenter retrospective study of patients with
      acute retinal arterial obstruction who underwent transthoracic echocardiography.
      SETTINGS: Four North American hospital centers. PATIENTS: One hundred patients
      with acute retinal artery obstruction in whom transthoracic echocardiography was
      performed. MAIN OUTCOME MEASURE: Anticoagulation or cardiac surgery based on
      abnormalities detected on transthoracic echocardiography. Transesophageal
      echocardiographic results were not evaluated, as they were rarely performed in
      our centers. Thus, the outcome measure was determined solely by the results of
      transthoracic echocardiography. RESULTS: Patients were divided into high- and low
      risk groups based on their history of cardioembolic risk factors or the presence
      of a cardiac murmur. Of 67 patients with no risk factors, 41 (61%) had normal
      echocardiographic study results and 26 (39%) had abnormalities detected, of whom
      only 1 (1.5%) received anticoagulation or cardiac surgery. The presence of 1 or
      more cardio-embolic risk factors increased the likelihood for anticoagulation or
      cardiac surgery 25 times (odds ratio = 25; 95% confidence interval = 3.04
      217.02). Although this result is clinically and statistically significant, it is
      possible that abnormalities missed by transthoracic methods may have been
      detected by transesophageal technology. CONCLUSIONS: In patients with acute
      retinal arterial obstruction at low cardioembolic risk, transthoracic
      echocardiography resulted in anticoagulation or cardiac surgery in 1 (1.5%) of 67
      patients. Routine transthoracic echocardiography without follow-up
      transesophageal echocardiography for patients identified as having abnormalities
      such as left ventricular hypertrophy or mitral annular calcification and who are
      at low cardioembolic risk rarely resulted in anticoagulation or cardiac surgery.

PMID- 8859077
TI  - Age-related macular degeneration and smoking. The Rotterdam Study.
AB  - OBJECTIVE: To assess the relation between cigarette smoking and age-related
      macular degeneration (AMD) in a population of elderly persons. DESIGN: A cross
      sectional, community-based study. SETTING: City district of Rotterdam, the
      Netherlands. PARTICIPANTS: A total of 6174 persons 55 years and older who
      participated in the Rotterdam Study. In 36 persons atrophic AMD and in 65 persons
      neovascular AMD were diagnosed. MAIN OUTCOME MEASURES: Age-related macular
      degeneration was diagnosed by evaluating fundus transparencies, smoking behavior
      was identified by interviewing subjects, and the presence of atherosclerosis was
      assessed by the ankle-arm systolic blood pressure index. Relative risks and 95%
      confidence intervals (CIs) were calculated using multivariate logistic regression
      analysis. RESULTS: In subjects younger than 85 years, current smokers had a 6.6
      fold increased risk of neovascular AMD vs those who had never smoked (95% CI, 2.8
      15.9). Former smokers had a 3.2-fold increased risk of neovascular AMD vs
      nonsmokers in this age group (95% CI, 1.4-7.4). These associations were not
      observed in subjects 85 years or older. Smoking was not associated with atrophic
      AMD. A strong increased risk of neovascular AMD was present in those who had
      smoked more than 10 pack-years (relative risk, 6.5; 95% CI, 2.9-14.8). Adjusting
      the results for atherosclerosis did not change the association. Persons who had
      quit smoking 20 or more years before the eye examination had no increased risk.
      CONCLUSIONS: The results provide evidence for a dose-response relationship
      between smoking and AMD, particularly in persons with the neovascular form of the
      disease.

PMID- 8859078
TI  - High-resolution magnetic resonance imaging of the intraorbital optic nerve and
      subarachnoid space in patients with papilledema and optic atrophy.
AB  - OBJECTIVE: To evaluate the orbital portion of the optic nerve and the
      subarachnoid space using fast spin-echo magnetic resonance imaging in normal
      subjects and in patients with papilledema or optic atrophy. DESIGN: Measurements
      of the optic nerve complex on coronal images were made using high-resolution
      magnetic resonance imaging with fast spin-echo sequences. PATIENTS: Twenty-one
      patients, including 5 patients with papilledema due to congenital hydrocephalus,
      intracranial tumors, or meningitis, as well as 16 patients with optic atrophy,
      were studied. Sixteen healthy volunteers served as controls. MAIN OUTCOME
      MEASURES: The longitudinal diameter of the optic nerve, the longitudinal outer
      diameter of the subarachnoid space, the diameter ratio, and the area of the
      subarachnoid space were determined. RESULTS: In normal subjects, the ring-shaped
      area of high signal intensity that represented the subarachnoid space was widest
      behind the globe, then narrowed toward the orbital apex. In patients with
      papilledema, the area of the subarachnoid space was markedly dilated, the optic
      nerve was compressed, and the nerve sheath was widened, resulting in a small
      diameter ratio compared with that of controls. Patients with pallor of the
      temporal aspect of the optic disc appeared to exhibit dilation of the
      subarachnoid space; the size of the optic nerve was decreased more than that of
      the nerve sheath, resulting in a small diameter ratio compared with controls.
      Patients with complete pallor of the disc, however, exhibited hyperintense optic
      nerve complexes without a ring-shaped appearance toward the orbital apex.
      CONCLUSION: Fast spin-echo magnetic resonance imaging appears useful for
      objectively evaluating the optic nerve and surrounding subarachnoid space in
      patients with papilledema and optic atrophy.

PMID- 8859079
TI  - Bilateral enophthalmos associated with hydrocephalus and ventriculoperitoneal
      shunting.
AB  - BACKGROUND: Progressive bilateral enophthalmos in the absence of previous trauma
      is rare. METHODS: Three patients with progressive bilateral severe enophthalmos
      whose only significant medical history was that of congenital hydrocephalus were
      treated by ventriculoperitoneal shunt placement. RESULTS: The patients
      demonstrated severe bilateral enophthalmos with poor eyelid apposition to the
      globes resulting in superficial keratopathy. Orbital computed tomographic scans
      confirmed the severe enophthalmos, with apparent reduced orbital fat volume.
      Orbital bony anatomy appeared normal. CONCLUSIONS: Bilateral progressive
      enophthalmos may be associated with hydrocephalus and ventriculoperitoneal
      shunting. The causal mechanism remains speculative.

PMID- 8859080
TI  - Correlation of vascular permeability factor/vascular endothelial growth factor
      with extraretinal neovascularization in the rat.
AB  - OBJECTIVE: To determine whether neovascularization was spatially correlated with
      the distribution of messenger RNA for vascular permeability factor/vascular
      endothelial growth factor (VPF/VEGF). METHODS: Neonatal rats were raised 8 days
      in 80% oxygen with daily intervals of relative hypoxia in room air, then
      transferred to room air for 5, 7, or 10 additional days. In situ hybridization
      for VPF/VEGF expression and avascular area were examined in retinas from oxygen
      exposed animals and room-air controls. Severity of neovascularization was scored.
      RESULTS: The inner nuclear layer of oxygen-exposed retinas exhibited a continuous
      intense band of VPF/VEGF messenger RNA expression across the peripheral avascular
      zone that dropped sharply in vascular retina. Neovascularization occurred
      adjacent to regions of greatest expression. Controls had much lower expression
      and smaller avascular regions. The VPF/VEGF messenger RNA expression was most
      intense in Muller cells, scattered astrocytes, and amacrine cells, strong in
      retinal pigment epithelium, and moderate in the remaining inner nuclear layer and
      ganglion cell layer. CONCLUSION: The expression of VPF/VEGF message was spatially
      and quantitatively correlated with the neovascularization.

PMID- 8859081
TI  - Regulation of vascular endothelial growth factor by oxygen in a model of
      retinopathy of prematurity.
AB  - OBJECTIVES: To investigate the role of vascular endothelial growth factor (VEGF)
      in the pathogenesis of the first phase of retinopathy of prematurity (ROP) and to
      examine the mechanism by which supplemental oxygen therapy might inhibit
      neovascularization in the second phase of ROP. METHODS: A novel combination of
      fluorescein-dextran perfusion and colorimetric whole-retina in situ hybridization
      was used to evaluate the expression of VEGF messenger RNA in relationship to the
      location of blood vessels in retinas from neonatal mice that were exposed to
      hyperoxia. Northern blot and immunoblot analyses were used to quantify the
      changes in VEGF messenger RNA and protein expression caused by hyperoxia. The
      ability of VEGF to prevent hyperoxia-induced vaso-obliteration was evaluated by
      injecting exogenous VEGF into the vitreous cavity prior to oxygen exposure.
      RESULTS: Vascular endothelial growth factor messenger RNA was produced in a
      reticular pattern just anterior to the developing blood vessels in normal retina
      on postnatal day 7. The expression of VEGF in the peripheral retina was down
      regulated by hyperoxia in conjunction with the arrest of growth and the loss of
      some of the developing vasculature. Total VEGF messenger RNA and protein levels
      in retinas from animals on postnatal day 7 were decreased 55% and 85%,
      respectively, after 6 hours in 75% oxygen. Vaso-obliteration was inhibited 57% by
      pretreatment of animals with exogenous VEGF. In animals with retinal ischemia
      secondary to loss of vasculature, treatment with supplemental oxygen therapy
      decreased stimulated retinal VEGF levels by approximately 70%. CONCLUSIONS: Down
      regulation of VEGF expression by hyperoxia may be partly responsible for the vaso
      obliteration and cessation of normal retinal blood vessel growth observed in
      premature infants in whom ROP develops. Hyperoxia also has the potential to be
      used therapeutically to down-regulate VEGF expression in hypoxic retina in the
      hope of limiting the neovascular complications of ROP. Based on these findings
      about the regulation of VEGF expression in the retina, an explanation of the
      pathogenesis of ROP is proposed.

PMID- 8859082
TI  - The anatomy of the common canaliculus.
AB  - BACKGROUND: The functional valve between the common canaliculus and the lacrimal
      sac has traditionally been attributed to the valve of Rosenmuller, although this
      anatomical structure has never been rigorously documented. OBJECTIVE: To define
      the anatomy of the canaliculus-sac junction. METHODS: Twelve rigid plastic casts
      of the lacrimal outflow systems were obtained in human cadaver specimens using a
      well-known biologic casting material (partially polkymerized monomer to which a
      catalyst and promoter were added). RESULTS: A consistent pattern of angulation
      within the canalicular system was documented. The canaliculi bend posteriorly
      behind the medial canthal tendon, then anteriorly to enter the sac at an acute
      mean angle of 58 degrees to the lateral wall of the sac. CONCLUSIONS: This
      consistent configuration at the canaliculus-sac junction has not been previously
      described and may contribute to the 1-way valve phenomenon seen in some lacrimal
      disorders.

PMID- 8859083
TI  - Glaucoma in Mongolia. A population-based survey in Hovsgol province, northern
      Mongolia.
AB  - OBJECTIVES: To determine the prevalence of glaucoma and suspect glaucoma, and to
      classify the cases detected according to mechanism. DESIGN: A population-based
      prevalence study. SETTING: Rural and urban locations in Hovsgol province,
      northern Mongolia. PARTICIPANTS: Nine hundred forty-two (94.2%) of 1000
      individuals 40 years of age and older were examined. MAIN OUTCOME MEASURE:
      Primary angle-closure glaucoma was diagnosed in subjects with previous acute or
      intermittent symptoms of angle closure and in individuals with an occludable
      angle and an intraocular pressure greater than 19 mm Hg or a glaucomatous visual
      field. RESULTS: The prevalence of manifest primary angle-closure glaucoma was
      1.4% (14 subjects). The prevalence of gonioscopically occludable angles was 6.4%
      (64 subjects, including those with glaucoma). Primary open-angle glaucoma was
      diagnosed in 5 subjects (prevalence, 0.5%). As all these subjects were older than
      60 years, the prevalence became 2.1% for this age group. Three cases (prevalence,
      0.3%) of secondary open-angle glaucoma were detected. No cases of secondary angle
      closure glaucoma were diagnosed. The prevalence of blindness was 1.2% (12
      subjects), and primary glaucoma accounted for one third of these cases (4
      subjects). CONCLUSIONS: We confirmed glaucoma as a major public health problem in
      northern Mongolia. Primary angle-closure glaucoma is more prevalent than primary
      open-angle glaucoma, supporting clinic-based data from other east Asian
      countries. Among the subjects examined, 97 (9.7%) had either manifest, latent, or
      suspect glaucoma. Neighboring populations may be similarly affected owing to a
      shared genetic heritage.

PMID- 8859085
TI  - Ophthalmology in Latin America.

PMID- 8859084
TI  - Prevalence and associations of retinal vein occlusion in Australia. The Blue
      Mountains Eye Study.
AB  - OBJECTIVE: To determine the prevalence and associations of retinal vein occlusion
      (RVO) in a defined older Australian population. DESIGN: Participants (N = 3654;
      age, > or = 49 years), representing 88% of the permanent residents from an area
      west of Sydney, Australia, underwent a detailed eye examination, including
      stereophotography (Zeiss). The diagnosis of RVO was made clinically and from
      photographic grading. RESULTS: Signs of RVO were found in 59 participants (1.6%;
      95% confidence interval, 1.3-1.9). The prevalence for each age-specific
      participant was as follows: 0.7%, younger than 60 years; 1.2%, 60 to 69 years;
      2.1%, 70 to 79 years; and 4.6%, 80 years or older. There was no significant sex
      difference in prevalence. Branch RVO was observed in 41 subjects (69.5%); of this
      number, 10 subjects had branch RVO outside the vascular arcade or in the nasal
      fundus and 3 subjects developed new vessels. Hemispheric RVO was found in 3
      subjects (5.1%), and central RVO was observed in 15 (25%); RVO was bilateral in 3
      subjects (5.1%). Visual acuity was affected most in the people with central RVO,
      with a visual acuity of 20/200 or less in 60% compared with 14% among the people
      with branch RVO. Retinal vein occlusion was the fifth most frequent cause of
      unilateral blindness in this population. Significant associations with RVO were
      found with glaucoma, hypertension, stroke, and angina. CONCLUSIONS: This study
      emphasizes RVO as an important cause of unilateral visual loss in an older
      population. The proportion of the 3 vein occlusion sites shows some differences
      from those of clinic-based reports and suggests a likely selection bias in
      previous clinic studies.

PMID- 8859086
TI  - Glaucoma in Mongolia.

PMID- 8859087
TI  - Vascular endothelial growth factor and the eye. Past, present and future.

PMID- 8859088
TI  - Congenital deficiency of abduction, associated with impairment of adduction,
      retraction movements, contraction of the palpebral fissure and oblique movements
      of the eye. 1905.

PMID- 8859089
TI  - Schwannoma of the bulbar conjunctiva.
AB  - We describe a conjunctival tumor that occurred in the limbic region of the left
      eye in a 37-year-old man. The mass was located beneath the conjunctival
      epithelium. It consisted of a well-demarcated proliferation of fusiform cells
      arranged in bundles in a fibrous stroma. Tumor cells strongly expressed S-100
      protein. On ultrastructural analysis, the tumor was composed of Schwann cells
      surrounded by a continuous basal lamina. These data led to the rare diagnosis of
      conjunctival schwannoma.

PMID- 8859090
TI  - Use of mitomycin C in the treatment of conjunctival primary acquired melanosis
      with atypia.
AB  - A patient who had primary acquired melanosis with marked atypia shown on
      histological studies received topical 0.02% mitomycin C for 2 weeks and 0.04%
      mitomycin C for an additional 2 weeks. Conjunctival biopsy specimens were
      obtained to evaluate the efficacy of the treatment. After the first course of
      mitomycin C administration, some decrease of conjunctival pigmentation was seen,
      and histological studies disclosed a lower degree of atypia. After the second
      application of mitomycin C, the pigmentation disappeared except for one small
      spot that contained only a few typical melanocytes on histological study. The
      clinical findings did not change during 7 months of follow-up. No adverse
      reactions to topical mitomycin C occurred except for mild conjunctival hyperemia
      at the end of the courses of treatment. Administration of topical mitomycin C may
      be an effective medical treatment for primary acquired melanosis with atypia.

PMID- 8859091
TI  - Early-onset posterior polymorphous dystrophy.
AB  - We report an unusual case of posterior polymorphous dystrophy in which corneal
      failure began within a few weeks of birth. Histopathologic findings included the
      presence of abnormal corneal endothelial cells with many microvilli on the
      surface. Descemet membrane was severely attenuated, and there was a thick
      posterior collagenous layer consisting of numerous fibroblast-like cells in a
      fibrillar extracellular matrix; ultrastructural immunocytochemistry showed this
      to contain tenascin, fibronectin, and collagen type I. Few histopathologic data
      on this disease at such an early age have been available, and to our knowledge,
      the composition of Descemet membrane has not been examined before. The microvilli
      covered cells are shown to be present from the outset of the disease, not just in
      long-standing cases as in previous reports; changes in Descemet membrane may
      influence disease evolution.

PMID- 8859092
TI  - Knowledge or noise. Scientific publication and the electronic journal.
AB  - Over the last few years, the Internet has grown exponentially and is developing a
      role in the exchange of scientific information. However, a number of problematic
      issues are associated with electronic publications, including limited
      transmission speed, undependable file longevity, poorly documented
      postpublication editing, copyright infringement, and cultural impediments to
      acceptance. By measure of citation frequency, electronic journals seem to have
      limited influence within scientific discourse, but this medium is as yet in its
      infancy. Since electronic publication enjoys many potential advantages over
      traditional print publication, it is expected to gain far greater influence over
      time. The American Medical Association group of publications recognizes this and
      intends to develop its electronic publications with attention to maintaining
      traditional critical scientific standards.

PMID- 8859093
TI  - A system for obtaining undiluted intraoperative vitreous biopsy samples.
AB  - For many analyses of the vitreous, it is essential to obtain undiluted vitreous
      specimens under sterile conditions intraoperatively. In this new technique, a
      metal device is integrated into the aspiration system. The device fits on
      standard laboratory plastic containers with integrated caps. Undiluted vitreous
      accumulates in the container, which is then removed and sent to the laboratory.
      With a new container in place, vitrectomy can be continued as usual. This
      technique is simple, safe, effective, and inexpensive.

PMID- 8859094
TI  - Sutureless pars plana vitrectomy through self-sealing sclerotomies.
AB  - A new technique of creating self-sealing pars plana sclerotomies is described. In
      a series of 50 consecutive vitrectomies, no complication was encountered related
      to this new technique. All of the 47 primary vitrectomy procedures performed had
      self-sealing sclerotomies that did not require suturing at the end of surgery.
      This type of wound construction allows for sutureless closure of sclerotomies
      with better control of intraoperative ocular pressure.

PMID- 8859095
TI  - Diffuse unilateral subacute neuroretinitis syndrome in Canada.

PMID- 8859096
TI  - Corneal endothelial cell loss after excimer laser keratectomy, associated with
      tranquilizers.

PMID- 8859097
TI  - Lipemia retinalis of prematurity.

PMID- 8859098
TI  - Choroidal effusion causing transient myopia after panretinal photocoagulation.

PMID- 8859099
TI  - Complete circumvention of central retinal artery and venous cilioretinal shunts
      in optic disc drusen.

PMID- 8859100
TI  - Unilateral eyelid retraction induced by a change from supine to sitting position.

PMID- 8859101
TI  - Nodular hidradenoma of the eyelid.

PMID- 8859102
TI  - Ectrodactyly-ectodermal dysplasia--clefting (EEC) syndrome.

PMID- 8859103
TI  - Epidermal nevus syndrome associated with a complex choristoma and a bilateral
      choroidal osteoma.

PMID- 8859104
TI  - von Hippel-Lindau disease and familial polyposis coli in the same family.

PMID- 8859105
TI  - Gyrate atrophy and choroidal neovascularization.

PMID- 8859106
TI  - Report of the joint meeting of the Japanese Glaucoma Society and the American
      Glaucoma Society, Vancouver, British Columbia, July 30-August 2, 1996.

PMID- 8859107
TI  - Decrease of intraocular pressure after subconjunctival injection of mitomycin in
      human glaucoma.

PMID- 8859108
TI  - Anatomic considerations in the implantation of the Ahmed glaucoma valve.

PMID- 8859109
TI  - The caliber of the needles used for injection or aspiration in surgical work.

PMID- 8859110
TI  - Cataract blindness: how eye surgeons can address the global problem.

PMID- 8859112
TI  - An inexpensive visualization method for laser suture lysis.

PMID- 8859111
TI  - Effect of arterial hypertension on the optic disc structure.

PMID- 8859113
TI  - Averaging excellence out?

PMID- 8859114
TI  - The interface of academic and community practice in medical and graduate medical
      education.
AB  - Historically, the interaction between academic departments of otolaryngology-head
      and neck surgery and the community practice of the specialty has been erratic,
      anecdotal, and often strained. A general sense of autonomy and isolationism that
      has characterized many university programs coupled with a paranoia on the part of
      many practitioners with respect to concerns about protecting their patient base
      have led to an uneasy relationship. Difficulties with managed care now threaten
      this relationship even more. It is clearly time to seek a solution that can
      enhance the educational opportunities for medical students and residents.

PMID- 8859115
TI  - The use of patient satisfaction data to assess the impact of continuous quality
      improvement efforts.
AB  - OBJECTIVE: To quantitatively compare patient satisfaction with the visit to an
      academic otolaryngology office before and after quality improvement efforts.
      DESIGN: Survey research of convenience sample of new patients. SETTING:
      Outpatients offices of the Department of Otolaryngology at Washington University
      School of Medicine, St Louis, Mo. PATIENTS: New patients seen between November
      1993 and March 1994 (phase 1) and November 1995 and February 1996 (phase 2).
      INTERVENTION: Numerous department-wide quality improvements efforts were begun
      between phase 1 and phase 2. The Visit Rating Questionnaire, a 9-item patient
      based questionnaire, was used to measure patient satisfaction. MAIN OUTCOME
      MEASURE: The percentage of patients who rated their visit overall as excellent.
      RESULTS: Overall, 973 patients participated. The percentage of patients who rated
      their overall visit as excellent was 570 (58%) of 1067, while it was 200 (41%) of
      491 for phase 1 and 370 (64%) of 576 for phase 2 (chi 2 = 63.8; P < .001). Using
      a process control chart for the percentage of patients who rated the visit as
      excellent demonstrated special cause variation, indicating that the continuous
      quality improvement efforts had made an impact on patient satisfaction.
      CONCLUSIONS: The impact of continuous quality improvement efforts can be
      documented with patient satisfaction measures. The techniques of statistical
      process control, including the use of control charts, can transform the data from
      these measures into information that allows for the evaluation of the
      effectiveness of continuous quality improvement efforts.

PMID- 8859116
TI  - Outpatient parotidectomy at the Fallon Clinic. The first 2 years.
AB  - OBJECTIVES: To determine whether outpatient parotidectomy can be performed safely
      with high patient satisfaction and to compare the cost of outpatient and
      inpatient parotidectomy. DESIGN: A retrospective review of hospital and office
      charts of patients admitted for elective outpatient and inpatient parotidectomy
      from 1992 to 1994. SETTING: A community teaching hospital and a multispecialty
      group practice that are part of an integrated health care system. PATIENTS:
      Nineteen consecutive outpatients and 13 concurrent inpatients admitted electively
      for parotidectomy. INTERVENTION: Outpatient and inpatient parotidectomies
      performed as a sole procedure. MAIN OUTCOME MEASURES: Duration of surgery and
      anesthesia, length of stay after surgery, complications, hospital and office
      charges, and a patient satisfaction survey. RESULTS: Twenty patients were
      admitted for outpatient parotidectomy; 19 (95%) went home the same day.
      Outpatients were discharged an average of 4 hours after surgery. No complications
      were specifically attributable to outpatient status. The mean savings on hospital
      based charges compared with a 1-night stay was $196 per case. The outpatients had
      2 more postoperative visits in the first 90 days after surgery; their
      postoperative care cost $72 per case more than for the inpatient group. Patient
      satisfaction was high, but it was higher in the inpatient group. CONCLUSIONS:
      Parotidectomy can be performed safely on outpatients. Outpatient satisfaction was
      high, but inpatient satisfaction was higher. The savings per case depends on the
      particular cost structure of the institution and may be modest compared with that
      of a 1-night inpatient stay. Savings are higher when compared with the diagnosis
      related group allowable stay of 4.0 days.

PMID- 8859117
TI  - Parotid gland dysfunction in an animal model of chronic graft-vs-host disease.
AB  - BACKGROUND: Xerostomia is observed in 85% of patients suffering from chronic
      graft-vs-host disease (cGVHD). The pathophysiological mechanism of the major
      salivary gland dysfunction is unclear. OBJECTIVE: To evaluate parotid gland
      function in a mouse model of cGVHD. DESIGN: The volume, flow rate, lag phase, and
      composition of secreted saliva were assessed in mice with cGVHD after pilocarpine
      stimulation (5 mg/kg) by cannulation of the main parotid excretory duct with
      polyethylene tubing. RESULTS: Significant reduction in the secreted saliva volume
      was observed in the mice with cGVHD compared with the syngeneic controls (39.1 +/
      2.9 microL/30 minutes and 71.2 +/- 5.7 microL/30 minutes, respectively) (P <
      .05). In addition, we observed a flattening of the normal salivary flow rate
      curve in the mice with cGVHD. The lag phase (time between pilocarpine stimulation
      and saliva secretion) was significantly longer in the cGVHD group than in the
      controls (2.5 +/- 0.3 vs 1.9 +/- 0.2 minutes) (P < .05). Sialochemical analysis
      showed a significant decrease in sodium level (42.1 +/- 1.9 vs 61.4 +/- 4.8
      mmol/L) (P < .01) and a significant increase in potassium level (20.0 +/- 1.2 vs
      15.1 +/- 1.2 mmol/L) (P < .05) in the saliva of the mice with cGVHD compared with
      syngeneic mice. Histopathological evaluation of the parotid glands demonstrated
      moderate lymphocyte infiltration and parenchymal destruction. CONCLUSION: The
      parotid gland dysfunctions leading to xerostomia observed in a mouse model of
      cGVHD may be of clinical importance.

PMID- 8859118
TI  - Polysomies of chromosomes 7 and 17 in head and neck squamous cell carcinomas.
AB  - OBJECTIVE: To determine the polysomies (ie, cells with > or = 3 chromosome
      copies) of chromosomes 7 and 17 in tumor tissue, histologically normal epithelia
      adjacent to the tumor (tumor-adjacent epithelia), and buccal epithelia distant
      from the tumor (tumor-distant epithelia) of head and neck squamous cell
      carcinomas. DESIGN: Nonfluorescent, nonisotopic, in situ hybridization using
      chromosome-specific centromeric DNA probes for chromosomes 7 and 17 was performed
      on the formalin-fixed, paraffin-embedded specimens from tumor and tumor-adjacent
      and tumor-distant epithelia of 19 patients with head and neck squamous cell
      carcinomas and from buccal epithelia of cancer-free control subjects who smoked
      and did not smoke cigarettes. MAIN OUTCOME MEASURES: Four hundred nuclei in tumor
      tissue and 200 nuclei in histologically normal epithelia were scored for
      hybridized signals in each sample. RESULTS: Buccal epithelia of cancer-free
      control subjects who smoked and did not smoke cigarettes showed no difference in
      the polysomies of chromosomes 7 and 17, respectively. The polysomies of
      chromosomes 7 and 17 in the tumor cells were higher than those in the tumor
      adjacent epithelia (P < .001 for both), tumor-distant epithelia (P < .001 for
      both), and buccal epithelia of cancer-free control subjects who smoked and did
      not smoke cigarettes (P < .001 for both). The polysomies of chromosomes 7 and 17
      in the tumor-adjacent epithelia were higher than those in the tumor-distant
      epithelia (P < .001 for both) and the control buccal epithelia (P = .002 and P <
      .001, respectively). The tumor-distant epithelia and the control buccal epithelia
      for the polysomies of chromosomes 7 and 17 had no differences. CONCLUSIONS: The
      finding of genotypic abnormalities in the tumor-adjacent epithelia supports the
      concept of field cancerization. Such genotypic parameters may provide a genetic
      basis for the development of an early recurrence or second primary tumors after
      therapeutic treatment of head and neck squamous cell carcinomas.

PMID- 8859119
TI  - CD4+ lymphocytes are increased in the sinus mucosa of children with chronic
      sinusitis.
AB  - OBJECTIVES: To quantitate lymphocyte subtypes in sinus tissues harvested from
      children with chronic sinusitis and coexisting asthma, allergies, and cystic
      fibrosis during functional endoscopic sinus surgery and compare them with those
      in normal adult sphenoid sinus mucosa. DESIGN: Immunohistochemical staining of
      surgical specimens with monoclonal antibodies against CD4 and CD8 surface
      antigens. SETTING: Tertiary medical center. PATIENTS: Thirty-two children who
      underwent functional endoscopic sinus surgery for chronic sinusitis refractory to
      medical treatment (median age, 8 years; range, 2-13 years) were divided into 3
      groups: 10 with asthma, 15 without asthma, and 7 with cystic fibrosis. Sphenoid
      sinus mucosa obtained from 10 adults (median age, 70 years) undergoing
      transsphenoidal hypophysectomy was used as control tissue. MAIN OUTCOME MEASURES:
      Numbers of CD4+ and CD8+ cells in the lamina propria and epithelium of surgical
      specimens. RESULTS: Significantly more CD4+ cells were in the sinus mucosa of
      patients with chronic sinusitis than in the normal sinus mucosa (P < .01), but
      there was no significant difference in the number of CD8+ cells (P = 4). Patients
      with chronic sinusitis with asthma, without asthma, and with cystic fibrosis all
      had increased numbers of CD4+ cells compared with sphenoid mucosa, with the
      difference reaching statistical significance only in the subgroup with chronic
      sinusitis without asthma (P < .001). The numbers of CD4+ cells were higher in
      patients with chronic sinusitis than in the sphenoid mucosa irrespective of
      allergic status. Significantly more CD4+ than CD8+ cells were in tissues from the
      patients with chronic sinusitis irrespective of concomitant diseases or allergic
      status. CD4+ and CD8+ cells were more numerous in the apical portion of the
      submucosa (immediately beneath the epithelium) than in the basal portion both in
      patients with chronic sinusitis and in normal sphenoid tissue. CONCLUSIONS:
      Children with chronic sinusitis have predominance of CD4+ cells in the sinus
      mucosa as compared with normal sphenoid tissue. This contrasts with published
      results in adults with chromic sinusitis, in whom CD8+ cells predominate in nasal
      polyps and the submucosa, possibly reflecting a difference in the immunologic
      response of children and adults.

PMID- 8859120
TI  - Anthropometric analysis of the female Latino nose. Revised aesthetic concepts and
      their surgical implications.
AB  - OBJECTIVE: To determine whether the present aesthetic concepts set forth for
      rhinoplasty in white patients can be applied to the ethnic variations seen in
      Latino women and, if not, to develop a reproducible means of analysis to serve as
      a guide for surgical correction. DESIGN: Cohort analytic study; criterion
      standard analysis of nasal aesthetics. PARTICIPANTS: Ninety-seven Latino women
      and 40 white women. INTERVENTIONS: Patients were separated according to
      geographic area of origin, either the Caribbean, Central America, or South
      America. Anthropometric measurements were obtained and nasal indexes were
      calculated. Results were compared with previously reported data for African
      Americans and whites. All patients underwent complete nasal photographic
      analysis. RESULTS: Caribbean subjects showed the greatest divergences from whites
      and resembled African-American anthropometric norms, whereas Central and South
      American subjects more closely resembled white norms. Two new aesthetic concepts
      were developed, the dorsal nasal breakpoint and the horizontal nasal axis, which
      have implications for aesthetic rhinoplasty. The breakpoint is a pivotal point
      along the nasal dorsum, structurally determined, which was found at different
      locations in all the groups studied. Caribbean subjects had breakpoints
      approximately halfway down the dorsum. Central and South Americans had
      breakpoints about two thirds of the way down the dorsum, and whites had
      breakpoints three fourths of the way down the dorsum. The horizontal rotation
      axis is present along a plane that connects the top of the ala with the tip.
      Rotation of the tip about this axis affects both the characteristics of the
      dorsal breakpoint and the final appearance of the nose. CONCLUSIONS: In general,
      Latino noses can be anthropometrically categorized as mesorrhine. When the
      geographically derived groups were examined individually, the Latino nose ranged
      from subplatyrrhine to paraleptorrhine. Surgical correction should be
      individualized, as each group requires correction of different nasal features.
      The dorsal breakpoint and the horizontal axis plane can act as nasal profile
      guides for surgical modifications that would achieve the current concept of the
      aesthetic nose.

PMID- 8859121
TI  - A new procedure for improvement of the ptotic melolabial fold.
AB  - OBJECTIVE: To demonstrate a new surgical technique for improving the ptotic
      melolabial fold. DESIGN: Case series. SETTING: University medical center.
      PATIENTS: Consecutive sample of 8 patients with ptotic melolabial folds.
      INTERVENTION: Preoperative and postoperative analysis evaluating surgical
      intervention. Surgical treatment of the ptotic melolabial fold consists of 3
      steps: removal of ptotic adipose tissue, excision of a crescent-shaped segment of
      skin along the nasoalar crease, and detachment of the dermal-connective tissue
      attachments. MAIN OUTCOME MEASURES: Evaluation of the improvement of the ptotic
      melolabial folds and correlation with concomitant aesthetic surgical procedures.
      CONCLUSIONS: Early results demonstrated improvement in the ptotic melolabial
      fold. Patients were pleased with the procedure, rating improvement as fair to
      good. The surgeons' evaluation correlated well with the patients' evaluation.

PMID- 8859122
TI  - Hereditary thyroglossal duct cysts.
AB  - OBJECTIVE: To examine the epidemiological and clinical characteristics of
      hereditary thyroglossal duct cysts (TGDCs). DATA SOURCES: A complete English
      language literature review, assisted by MEDLINE and BIOSIS, of hereditary cases
      of TGDC was performed between 1975 and 1996. Three new cases from our institution
      were included in the study. STUDY POPULATION: Patients with a diagnosis of
      hereditary TGDC. DATA EXTRACTION: All case reports were reviewed by multiple
      observers to confirm the diagnosis of hereditary TGDC. DATA SYNTHESIS: A review
      of the literature revealed that a hereditary pattern has been described in 18
      patients from 6 families; 11 of the 18 cases were reported in the United States.
      We report 3 new cases of TGDC herein, bringing the total of US cases to 14. In
      all 14 US cases, the patients were female presented at a mean age of 6.1 years,
      and had a predominantly autosomal dominant inheritance pattern. These findings
      are in sharp contrast to those in international cases (n = 7), in which only 29%
      of the patients were female and the mean age at presentation was much older (16.2
      years). An autosomal dominant pattern of inheritance was found in 2 of 3 foreign
      families. Interestingly, the patients with an autosomal dominant pattern of
      inheritance were older than those with an autosomal recessive pattern (13.9 years
      vs 6.2 years, respectively). CONCLUSIONS: Cases of hereditary TGDC are female
      predominant and usually have an autosomal dominant pattern of inheritance. The
      sexual bias may be explained by genetic imprinting. Although no racial
      differences were noted in our study, distinct variations in presentation based on
      nationality were present. The recurrence rate after a Sistrunk procedure is
      similar to that in nonhereditary cases.

PMID- 8859123
TI  - Cochlear histopathologic characteristics following long-term implantation. Safety
      studies in the young monkey.
AB  - OBJECTIVE: To evaluate the safety of cochlear implantation in children 2 years of
      age or younger using a non-human primate model. DESIGN: Histopathologic study.
      SUBJECTS: Five macaque monkeys. INTERVENTION: A commercially produced electrode
      array was implanted for 3 years. RESULTS: Histologic examination demonstrated the
      biocompatibility of the scala tympani electrode array. Limited soft-tissue growth
      and new bone growth were observed in the lower basal turn. There was no evidence
      of intracochlear infection. Evidence of minimal insertion trauma was seen. Hair
      cell loss was, in general, confined to the region of the electrode array, with
      normal hair cell populations toward the apex, although there was evidence of hair
      cell preservation adjacent to the array. At least 20% of spiral ganglion cells
      were preserved even in regions with a smaller proportion of hair cells.
      CONCLUSIONS: Even after extended periods of implantation, the electrode array is
      well tolerated, and there is substantial preservation of neural elements.

PMID- 8859124
TI  - Effects of intraoperative tissue expansion and skin flaps on wound closing
      tensions.
AB  - OBJECTIVE: To evaluate the effect on wound closing tension of acute tissue
      expansion combined with development of a rectangular flap compared with simple
      undermining with rectangular flap development. DESIGN: Wound closing tensions of
      30 acutely expanded skin sites and 30 matched undermined sites were compared
      after development of rectangular flaps. Analysis of covariance was used to
      determine statistical significance. SUBJECTS: Ten domestic piglets. RESULTS: When
      mean values of wound closing tension for the expanded rectangular flap were
      compared with those of the undermined rectangular flap a significant difference
      was found at the intermediate points along the curve for tension vs length of
      skin stretch. CONCLUSION: For small lesions, acute tissue expansion in
      conjunction with the use of a rectangular flap results in decreased wound closing
      tensions when compared with simple undermining with the use of a flap.

PMID- 8859126
TI  - Biomechanics of the helical rim advancement flap.
AB  - OBJECTIVES: To determine how helical rim closure with advancement flaps affects
      ear length and cupping, to compare the tension of closure with wedge excision and
      helical rim advancement and the effects of 3 tension-decreasing surgical
      techniques, and to review clinical experience with this flap. DESIGN: The
      laboratory study was performed on 6 fresh cadaver ears, by means of sequential
      excision of tissue, and closure tension was measured with a strain gauge. Results
      obtained in 10 patients were reviewed. SETTING: University referral hospital.
      PATIENTS: Ten patients with helical rim defects treated with helical rim
      advancement flaps. INTERVENTION: In cadaver ears, a helical rim defect of 5 mm
      was enlarged sequentially to 10 mm, 15 mm, and finally 20 mm. In the patients,
      defects of the helical rim caused by trauma or tumor were closed by this helical
      rim advancement flap method. MAIN OUTCOME MEASURES: For the laboratory study, the
      outcome measures were tension of closure of the defect, ear length, and ear
      cupping. For the review of cases, outcome was determination of perioperative
      complications and the patient's and surgeon's judgment of cosmetic appearance.
      RESULTS: Closure of a helical rim defect with advancement flaps caused minor
      shortening and moderate cupping of the ear. The tension of closure was decreased
      by extending the inferior incision into the earlobe, creating a Burow triangle,
      and shaving cartilage from the scapha. Both the Burow triangle and the scaphal
      shave caused mild increases in ear cupping. CONCLUSION: Helical rim advancement
      flaps provide satisfactory closure of helical rim defects up to at least 20 mm
      (longer in some ears) with excellent preservation of normal anatomic landmarks
      and a near-normal appearance of the reconstructed ear.

PMID- 8859125
TI  - Effect of topical diphenhydramine on the laryngeal chemoreflex.
AB  - OBJECTIVE: To study diphenhydramine nebulization as a clinically applicable
      method for blunting laryngeal chemoreflex (LCR)-associated apnea. INTERVENTIONS:
      Fourteen piglets aged 15 to 18 days were studied. In 7 piglets, diphenhydramine
      hydrochloride (5.0 mg/kg) was nebulized onto the laryngeal mucosa after a
      baseline response was obtained. RESULTS: After a 10-minute waiting period, the
      mean +/- SD LCR-induced apnea duration decreased from 29 +/- 13 seconds in the
      control animals to 15 +/- 5 seconds in the treated group (P = .02, 1-factor
      analysis of variance). After 1 hour, no treatment effect was seen. CONCLUSIONS:
      Nebulization of diphenhydramine can effectively reduce LCR-induced apnea for a
      short time. Nebulization of longer-acting agents may provide an effective
      prophylaxis of LCR-induced apnea.

PMID- 8859127
TI  - Stapes fixation associated with symphalangia.
AB  - We describe a 10-year-old boy and his 9-year-old sister, both of whom had
      bilateral hearing loss associated with ankylosis of the proximal interphalangeal
      joints (symphalangia). They had no other abnormal findings except hearing loss
      and ankylosis of the joints of some fingers and toes on systemic examination. The
      cause of conductive hearing loss in both cases was bony fusion between the stapes
      and the bone of the oval window niche. There were no other anatomical
      abnormalities in the middle or the external ear. The patients' hearing improved
      markedly after stapes surgery. Histopathologic examination of the stapes revealed
      an abnormal zone of ossification near the anterior annular ligament and
      calcification in the annular ligament, which seemed to be the cause of the stapes
      fixation.

PMID- 8859128
TI  - Pathologic quiz case 1. Solitary fibrous tumor (SFT) of the orbit.

PMID- 8859129
TI  - Pathologic quiz case 2. Cherubism.

PMID- 8859130
TI  - Parental human immunodeficiency virus infection. New challenges for the
      pediatrician.

PMID- 8859131
TI  - The psychological effects of parental human immunodeficiency virus infection on
      uninfected children.
AB  - OBJECTIVES: To assess the mental health of children of mothers infected with the
      human immunodeficiency virus. DESIGNS: Matched comparison of 26 children of
      mothers infected with the human immunodeficiency virus and 26 children with no
      experience of human immunodeficiency virus infection within their families.
      SETTINGS: Subject children were identified through hospital acquired
      immunodeficiency syndrome clinics and comparison children were identified through
      the primary care center of the same hospital. PARTICIPANTS: Subjects and controls
      were aged 6 to 16 years and matched by age, sex, race, and maternal marital and
      employment status. MAIN OUTCOME MEASURES: Parents completed the Child Behavior
      Checklist and the children completed the Revised Children's Manifest Anxiety
      Scale and the Children's Depression Inventory. RESULTS: Controlling for
      confounding variables, subjects were found by the Child Behavior Checklist to be
      significantly more withdrawn (P < .05) and to have more problems with attention
      (P < .005) than controls, although total Child Behavior Checklist scores were not
      significantly different. Compared with control children, the subject children
      reported more depression on the Children's Depression Inventory (P < .05) but
      were not more anxious. However, compared with children of asymptomatic mothers,
      the children of symptomatic mothers were reported to be significantly more
      anxious and/or depressed on the Child Behavior Checklist (P < .01) and the
      children reported more anxiety on the Revised Children's Manifest Anxiety Scale
      (P < .05). CONCLUSIONS: This study focusing specifically on uninfected children
      in families affected by the human immunodeficiency virus demonstrates some of the
      psychological ramifications of this disease. Larger studies are required to
      identify factors that contribute to the vulnerabilities and resilience of such
      children. Attention needs to focus on ameliorating these adverse effects on the
      children of the acquired immunodeficiency syndrome epidemic.

PMID- 8859132
TI  - Attitudes about sibling visitation in the neonatal intensive care unit.
AB  - OBJECTIVE: To survey the attitudes and recommendations of staff members before
      and after the implementation of sibling visitation in a neonatal intensive care
      unit. DESIGN: Staff survey conducted before (1992) and after (1993) the
      implementation of sibling visitation. SETTING: A perinatal tertiary care center.
      PARTICIPANTS: Staff members including physicians, nurses, respiratory therapists,
      social workers, and unit clerks (n = 139 in 1992; n = 120 in 1993). MEASUREMENTS
      AND MAIN RESULTS: A 7-point Likert scale survey (1 = strongly disagree: 7 =
      strongly agree) was designed for the study. In both 1992 and 1993, the staff most
      strongly agreed that visitation requires special supervision, should have
      designated times, increases sibling knowledge, enhances sibling attachment to the
      baby, and increases family satisfaction. Wilcoxon rank sum tests comparing the
      staff across the 2 years indicated substantial attitudinal changes in favor of
      sibling visitation, including less perceived interference with nursing care and
      nursery routines (P < .01) and less concern about the infants' risk of
      respiratory infection and exposure to chickenpox (P < .05). There was greater
      attitudinal agreement between disciplines in 1993 than in 1992, suggesting better
      staff consensus about sibling visitation following its implementation. The
      recommended minimum age for visitation was 4.67 years and 4.05 years in 1992 and
      1993, respectively. Brief visits of 10 to 15 minutes' duration were consistently
      recommended. Staff rated the sibling visitation program as successful (median =
      6) on a scale ranging from 1 (very poor) to 7 (very successful). CONCLUSIONS:
      Staff members have concerns about sibling visitation that include increased risk
      of infection, organization, and supervision. A sibling visitation program that
      addresses these concerns can be successfully implemented and supported by staff,
      thereby fostering family-centered care in the neonatal intensive care unit.

PMID- 8859133
TI  - Methodological issues in determining rates of childhood immunization in office
      practice. A study from pediatric research in office settings (PROS).
AB  - OBJECTIVE: To compare 3 methods for measuring pediatric office immunization
      rates. DESIGN: Retrospective and prospective cross-sectional surveys. PATIENTS:
      Children 2 and 3 years old from 15 pediatric practices in 11 states. METHODS:
      Immunization rates were determined for each practice using 3 methods. The
      Consecutive method used data from the practice's medical records of patients seen
      consecutively in the office; the Chart method used data from randomly selected
      practice medical records; and the Active method (reference standard) used a
      combination of medical record data with a telephone interview to collect
      additional immunization data and current patient status, using data only on
      current patients. Analyses were based on a mean of 57, 62, and 51 (Consecutive,
      Chart, and Active method, respectively) patients per practice. Patients were
      considered fully immunized if they had received 4 doses of DTP/DT vaccine, 3
      doses of OPV/IPV, and 1 dose of MMR vaccine by their second birthday Comparisons
      were made using the paired t test. RESULTS: The mean immunization rate by method
      was Consecutive, 81.5% (range, 51%-97%); Chart, 71.6% (range, 42%-94%); and
      Active, 79.6% (range, 53%-96%). Within a given practice, the differences between
      methods varied considerably (0 to 28 percentage points). The mean difference from
      the reference standard Active method was 8 percentage points (P < .001) for the
      Chart method and -1.9 percentage points (P = .36) for the Consecutive method. The
      largest difference was between the Consecutive and Chart methods (mean
      difference, 9.9 percentage points; P = .003). Practitioners uniformly found the
      Consecutive method easiest to implement. CONCLUSIONS: Practice-specific
      immunization rates are one of the few objective measures of the quality of
      preventive pediatric care. Pediatric practices monitoring their immunization
      rates should consider using the Consecutive method, a simple, acceptable, and
      valid measure of practice immunization rate.

PMID- 8859134
TI  - Family life 1 year after infantile colic.
AB  - OBJECTIVE: To determine the persistence of family psychological characteristics
      associated with infantile colic. DESIGN: A 1-year follow-up survey of families
      with colicky infants was carried out. The family interview was used to evaluate
      the psychological factors of colicky and control families. PARTICIPANTS: A total
      of 59 families with a colicky infant and 58 control families were enrolled in the
      initial evaluation in the population-based study. On the basis of a structured
      diary of the infant's crying, filled in by the parents, 3 groups of families were
      formed: severe colic group (n = 36), moderate colic group (n = 23), and control
      group (n = 58). The families were interviewed when the infants were 2 and 12
      months old. The Beavers-Timberlawn Family Evaluation Scale and the Oulu Family
      Assessment Scale were used. Thirty-two families (89%) from the severe colic
      group, 17 (74%) from the moderate colic group, and 49 (84%) from the control
      group participated in the 1-year assessment. RESULTS: At the 1-year assessment,
      the structural profile of the families did not differ between the groups.
      However, families in the severe colic group had more difficulties in
      communication, more unresolved conflicts, more dissatisfaction, and greater lack
      of empathy than families in the other groups. Furthermore, there was less
      flexibility in both colic groups than in the control group. During the follow-up
      period, coalition between parents in the moderate colic group became stronger
      compared with the first assessment, and the atmosphere improved significantly in
      all 3 study groups. However, the amount of empathy decreased in the severe colic
      group. CONCLUSIONS: Our study shows that certain family characteristics
      associated with severe infantile colic persist. Families in the moderate colic
      group coped nearly as well as families in the control group. The family mood had
      improved a lot in all families when the infant was 1 year old.

PMID- 8859135
TI  - Absence of negative attitudes toward childbearing among pregnant teenagers. A
      risk factor for a rapid repeat pregnancy?
AB  - OBJECTIVE: To test the hypothesis that adolescent mothers who conceive again
      during the first postpartum year express more positive attitudes toward
      childbearing while pregnant than do adolescent mothers who postpone further
      childbearing. METHOD: Prospective, cross-sectional, population-based survey.
      DESIGN: A racially diverse group of 200 consecutively enrolled, poor, pregnant 13
      to 18-year-old patients in an adolescent-oriented maternity program were
      interviewed to determine why they had not used contraceptives prior to the index
      conception. The study participants were followed up prospectively for the first
      postpartum year. The data analysis included t tests, chi 2 tests, analysis of
      variance, and logistic regressions. RESULTS: The repeat pregnancy rate was 11.5%
      during the first postpartum year. As hypothesized, those who became pregnant
      again were more likely to have expressed positive attitudes toward childbearing
      during the index pregnancy (60.9% vs 39.6%; P = .05; odds ratio = 2.38; 95%
      confidence interval, 0.96-5.90). In addition, those who conceived again were more
      likely to have had a prior miscarriage, dropped out of school, abused illicit
      substances, moved away from home, and reported inadequate family support during
      the index pregnancy, and were less likely to plan to use levonorgestrel
      (Norplant) following delivery. The best model for predicting repeat pregnancy
      included education status, postpartum plans for Norplant use, and miscarriage
      history. Having a positive attitude toward childbearing during pregnancy was not
      included in the final model because it did not contribute to the model or affect
      any of the other parameters in the model. CONCLUSIONS: The sexually active
      teenaged mother who does not use contraception poses a perplexing diagnostic
      dilemma. The differential diagnosis is a long, complex one that includes
      ambivalent feelings about postponing future childbearing. This study demonstrates
      an indirect association between positive attitudes toward childbearing during
      pregnancy and repeat adolescent pregnancy. Our finding that this association
      operates through common linkages between maternal educational and contraceptive
      plans and both positive attitudes toward childbearing and repeat adolescent
      pregnancy suggests that interventions specifically targeting these underlying
      causes could reduce the unsafe sexual practices that persist among the
      participants in comprehensive adolescent-oriented maternity programs.

PMID- 8859136
TI  - Lidocaine for lumbar punctures. A help not a hindrance.
AB  - OBJECTIVE: To determine whether premedication for lumbar puncture (LP) with
      lidocaine hinders collection of cerebrospinal fluid (CSF) through either
      increased number of attempts or increased incidence of traumatic punctures.
      DESIGN: A randomized controlled trial. SETTING: The pediatric emergency
      department of an innercity teaching hospital. PATIENTS: A convenience sample of
      100 children, younger than 3 years, who required an LP as part of their
      diagnostic workup. INTERVENTION: Patients were randomized to receive either
      lidocaine or no local anesthetic before undergoing an LP. MAIN OUTCOME MEASURES:
      Comparison of the number of attempts needed to obtain CSF and the number of
      traumatic LPs between the lidocaine-treated and no local anesthetic groups.
      RESULTS: The 51 patients randomized to receive lidocaine did not differ markedly
      in age from the 49 patients randomized to receive no local anesthetic. Ease of
      obtaining CSF, as measured by number of attempts, did not differ with 59% of the
      patients in each group requiring 1 attempt. Defining a traumatic LP as more than
      1000 x 10(6)/L red blood cells in the CSF showed notably more traumatic LPs in
      the lidocaine-treated group. Defining a traumatic LP as one with more than 10,000
      x 10(6)/L red blood cells in the CSF showed no significant difference in the
      number of traumatic LPs whether or not the patient was premedicated with
      lidocaine. The level of experience of the physician performing the LP did not
      affect the outcome. CONCLUSIONS: Premedication with lidocaine for an LP does not
      binder the ease of obtaining CSF. The clinical relevance of a greater number of
      traumatic LPs in the lidocaine-treated group is questionable because this finding
      is negated when traumatic is defined as more than 10,000 x 10(6)/L CSF red blood
      cells. Based on these results, we advocate premedication with a local anesthetic
      when an LP is performed in the pediatric emergency department.

PMID- 8859137
TI  - Attitudes of academic pediatricians with a specific interest in child abuse
      toward the spanking of children.
AB  - OBJECTIVE: To evaluate the attitudes of academic child abuse professionals toward
      spanking, the effect of context and mode of administration on their attitudes
      toward spanking appropriateness, and what they teach residents about spanking.
      DESIGN: A survey. PARTICIPANTS: Convenience sample of 114 members of the
      Ambulatory Pediatric Association's Special Interest Group on Child Abuse and
      Neglect. MAIN OUTCOME MEASURES: Respondents were asked if spanking was an
      appropriate disciplinary option for children 2, 5, and 8 years of age who refused
      to go to bed, ran into the streets without looking, or hit a playmate.
      Respondents also rated the appropriateness of spanking in 6 additional scenarios
      where the setting in which spanking occurred was varied. Respondent's teaching
      practices relative to spanking observed during a clinic visit were also elicited.
      RESULTS: The response rate was 70%; 39% thought spanking was appropriate
      sometimes. The context and mode of spanking affected the acceptance of spanking.
      All respondents thought that some response was appropriate when spanking was
      observed during a continuity clinic visit. However, only 29% of respondents
      taught residents how to handle such situations. CONCLUSIONS: Most academic child
      abuse professionals believe that spanking is inappropriate and their beliefs are
      influenced by the context in which spanking occurs. Little is taught about how to
      manage spanking observed in a clinical setting.

PMID- 8859138
TI  - Influence of family functioning and income on vaccination in inner-city health
      centers.
AB  - OBJECTIVES: To assess family functioning and consumer decision-making about
      vaccinations and to compare the results with age at vaccination. DESIGN: Self
      administered survey that was mailed to parents with comparison to vaccination
      records from chart audits. SETTINGS: Two inner-city health centers in Pittsburgh,
      Pa, that receive free vaccine supplies. PARTICIPANTS: Systematic sample from the
      billing computer records of parents whose children were aged 2 to 4 years as of
      July 2, 1993. INTERVENTIONS: The survey used simplified versions of the Family
      Profile and the Triandis model of consumer decision-making that includes
      perceived consequences of vaccinations, attitude about vaccinations, social
      influences, and facilitating conditions (eg, ease of obtaining an appointment).
      MAIN OUTCOME MEASURES: Variables associated with age at vaccination for third
      diphtheria and tetanus toxoids and pertussis vaccine immunization and first
      measles-mumps-rubella immunization. RESULTS: Of 395 families, 167 responded.
      Higher family dysfunction scores and lower family concordance scores each were
      associated with receiving first measles-mumps-rubella vaccination (P < or = .02)
      and third diphtheria and tetanus toxoids and pertussis vaccination (P < = .02) at
      later ages. Many (30%-54%) of the respondents reported that they knew little
      about the risks and benefits of vaccination. However, knowledge about vaccines
      was not associated with vaccination status. Those respondents with an annual
      income of less than $10000 received the first measles-mumps-rubella vaccination
      later than those with an annual income $10000 or greater (P < .02) when the data
      were analyzed by age at vaccination but not when the data were analyzed as on
      time vs late vaccinations. CONCLUSIONS: To increase vaccination rates in
      innercity clinics, strategies need to consider family dysfunction and income and
      not merely focus on education. The use of age at vaccination as a continuous
      variable offers advantages over the dichotomy of immunized vs not immunized.

PMID- 8859139
TI  - Racial disparities in outcomes of military and civilian births in California.
AB  - OBJECTIVE: To examine racial disparities in prenatal care utilization, birth
      weight, and fetal and neonatal mortality in a population for whom financial
      barriers to health care services are minimal. STUDY-DESIGN: Using linked birth,
      fetal death, and infant death certificate files, we examined prenatal care
      utilization, birth weight distribution, and fetal and neonatal mortality rates
      for all white and black births occurring in military hospitals in California from
      January 1, 1981, to December 31, 1985. These patterns were compared with the
      experience of their civilian counterparts during the same time period. RESULTS:
      Black mothers had higher percentages of births occurring in teenaged and
      unmarried mothers than did white mothers in military and civilian populations.
      First-trimester prenatal care initiation was lower for blacks in the military
      (relative risk, 0.79; 95% confidence interval, 0.75-0.82) and civilian (relative
      risk, 0.51; 95% confidence interval, 0.50-0.52) populations. However, the scale
      of the disparity in prenatal care utilization was significantly smaller (P <
      .001) in the military group. Rates of low birth weight and fetal and neonatal
      mortality among blacks were elevated in the military and civilian groups.
      However, the racial disparity in low birth weight was significantly smaller in
      the military group (P < .01 and P < .001, respectively). CONCLUSIONS: In
      populations with decreased financial barriers to health care, racial disparities
      in prenatal care use and low birth weight were reduced. However, the persistence
      of significant disparities suggests that more comprehensive strategies will be
      required to ensure equity in birth and neonatal outcome.

PMID- 8859141
TI  - Variability in physicians' reported ordering and perceived reassurance value of
      diagnostic tests in children with 'growing pains'.
AB  - OBJECTIVES: To determine the variability in the reported ordering of tests and
      treatment and to determine physicians' perceptions of the reassurance value to
      families of diagnostic tests in children with "growing pains." DESIGN: Cross
      sectional survey using a mailed questionnaire. SETTINGS: Primary care and
      referral practices in Toronto, Ontario. PARTICIPANTS: University-affiliated
      primary care pediatricians and family physicians were surveyed, as well as all
      pediatric orthopedic surgeons and pediatric rheumatologists in Ontario. Pediatric
      orthopedic surgeons and pediatric rheumatologists were combined into a single
      group. MAIN OUTCOME MEASURES: Frequency of office visits because of growing
      pains, frequency of diagnostic testing, management strategies for these children,
      and physicians' perceptions of the reassurance value of diagnostic tests.
      RESULTS: Of 205 eligible physicians, 181 (88.3%) responded. The median reported
      frequency of office visits because of growing pains was 1%. Compared with the
      other physician groups, family physicians were significantly more likely to order
      a determination of the hemoglobin level (P = .003), erythrocyte sedimentation
      rate (P = .01), white blood cell count (P = .01), and differential blood cell
      count (P = .003), but not imaging tests. Family physicians were also more likely
      to order diagnostic tests when they were under parental pressure to do so (P =
      .001) or for the child with repeated visits (P = .02). In total, 86% of pediatric
      orthopedic surgeons and pediatric rheumatologists, 95% of pediatricians, and 100%
      of family physicians perceived normal test results to be reassuring to parents.
      Treatment strategies were similar across the 3 physician groups. CONCLUSIONS: The
      frequency of diagnostic testing varied among physician groups. Virtually all
      physicians perceived normal test results to be reassuring to families.

PMID- 8859140
TI  - Postnatal variations of growth hormone bioactivity and of growth hormone
      dependent factors.
AB  - OBJECTIVE: To evaluate whether the low insulinlike growth factor I (IGF-I) levels
      that are observed in the neonate depend on the biological inactivity of the
      molecular forms of growth hormone (GH) or on the immaturity of the hepatic GH
      receptors during the early postnatal period. MATERIALS AND METHODS: Serum samples
      were collected from 60 normal full-term neonates on day 5 and at 1 and 4 months
      of age to evaluate the GH concentrations by using both an immunofluorometric
      assay and Nb2 cell bioassay, as well as the GH-binding protein, IGF-I, and IGF
      binding protein 3 values by radioimmunoassay. RESULTS: Five-day-old neonates
      showed significantly higher (P < .001) mean +/- SEM GH levels that were measured
      by using the immunofluorometric assay (27.22 +/- 1.62 micrograms/L) and Nb2 cell
      bioassay (3.56 +/- 0.14 U/mL) compared with those levels in 11 prepubertal
      children who were studied as control subjects (1.26 +/- 0.28 micrograms/L and
      0.74 +/- 0.08 U/mL, respectively). At 1 and 4 months of age, GH values that were
      measured by using both the immunofluorometric assay (9.15 +/- 0.89 and 2.58 +/-
      0.32 micrograms/L, respectively) and Nb2 cell bioassay (2.52 +/- 0.11 and 1.71 +/
      0.15 U/mL, respectively) were decreased significantly (P < .001). In 5-day-old
      neonates, we observed significantly lower (P < .001) serum GH-binding protein
      (9.73% +/- 0.42%), IGF-I (67.63 +/- 5.20 ng/mL), and IGF-binding protein 3 (1.46
      +/- 0.17 mg/L) concentrations compared with those in the prepubertal children
      (30.74% +/- 2.01%, 210 +/- 25 ng/mL, and 3.08 +/- 0.22 mg/L, respectively). At 1
      month of age, serum GH-binding protein (16.00% +/- 0.70%) and IGF-binding protein
      3 (2.96 +/- 0.30 mg/L) values were increased significantly (P < .001), while IGF
      I levels (72.55 +/- 7.6 ng/mL, P = .09) were not increased. Serum IGF-I values
      were increased significantly (P < .005) at 4 months of age (97.94 +/- 9.68
      ng/mL). CONCLUSION: The interaction of bioactive molecular forms of GH with the
      increased hepatic GH receptors induces the rise in postnatal IGF-I levels in
      early infancy.

PMID- 8859142
TI  - Mortality from intentional and unintentional injury among infants of young
      mothers in Colorado, 1986 to 1992.
AB  - OBJECTIVES: To investigate the association between maternal age and other risk
      factors and infant injury deaths in the state of Colorado from 1986 to 1992.
      DESIGN: A retrospective cohort design was used to compare rates of unintentional
      and intentional infant injury mortality by maternal age group. A case-control
      design explored the importance of various risk factors, particularly maternal
      age, using multivariate logistic regression. PARTICIPANTS: The 2 case groups
      comprised all unintentional and intentional injury deaths in the first year of
      life. The control group was a random sample of both survivors and noninjury
      deaths selected from the entire birth cohort. RESULTS: The infant injury
      mortality rate for the 322766 live births in Colorado from 1986 to 1992 was 3.1
      per 10000. Intentional injury death rates were highest for infants of teenaged
      mothers, peaking at 10.5 per 10000 live births for mothers aged 16 years.
      Unintentional injury death rates were highest for infants of mothers aged 20 to
      24 years, peaking at 3.7 per 10000 live births for 22-year-old mothers. For
      intentional injury death, maternal marital status had a significant impact on
      maternal age; compared with the baseline group of married mothers older than 24
      years, significantly higher risks were observed for infants of teenagers who were
      married (odds ratio [OR] = 32.0; 95% confidence interval[CI], 9.9-104.0) but also
      in infants of older mothers who were unmarried (OR = 3.6; 95% CI, 1.0-13.0 for
      unmarried mothers aged 20-24 years and (OR = 7.7; 95% CI, 2.4-25.0 for those > 24
      years). Black race (OR = 3.5; 95% CI, 1.4-9.4) was also associated with
      intentional injury death. For unintentional injury death, the highest risk was
      for infants of mothers aged 20 to 24 years and unmarried (OR = 3.9; 95% CI, 1.7
      9.3). Risk was also elevated for infants of married teenaged mothers (OR = 3.5;
      95% CI, 0.7-17.8) but was not significantly different from the baseline group for
      unmarried teenagers, married 20- to 24-year-old mothers, or unmarried mothers
      aged 25 years or older. Risk was increased by the presence of older siblings (OR
      = 1.5 per sibling; 95% CI, 1.2-2.0). CONCLUSIONS: Maternal age and marital status
      significantly affect the rate of both unintentional and intentional infant injury
      mortality. These results suggest that child abuse prevention strategies should be
      targeted to teenaged mothers, and that strategies designed to prevent
      unintentional injuries should focus particularly on parents or caretakers of
      infants born to unmarried mothers in their early 20s as well as married
      teenagers.

PMID- 8859143
TI  - Rethinking the threshold for an abnormal capillary blood lead screening test.
AB  - OBJECTIVES: To examine the test characteristics of the capillary blood lead
      screening test as a predictor of elevated venous blood lead levels, using
      receiver operating characteristic (ROC) curves. To consider a rational capillary
      blood lead cutoff value in the context of what has been learned about the
      screening test and what is understood about the clinical course of children with
      elevated blood lead levels in the mild range (0.48-0.92 mumol/L [10-19
      micrograms/dL]). DESIGN: In a clinical trial, 513 urban children aged 6 years and
      younger were screened for lead exposure. Paired samples of venous blood were
      drawn from all children. For these children we examine the ROC curves for
      capillary blood lead levels as a predictor of elevated venous blood lead levels
      above 2 thresholds, 0.48 and 0.97 mumol/L (10 and 20 micrograms/dL). Contaminated
      capillary specimens were defined as those in which the capillary result exceeded
      the venous result by 0.12 mumol/L (2.5 micrograms/dL) or more (n = 49). MAIN
      OUTCOME MEASURES: Test sensitivity and false-positive rate (equal to 1
      specificity) as a function of the capillary screening cutoff value. Area under
      the ROC curve as a measure of screening test performance. RESULTS: Venous blood
      lead levels were 0.48 mumol/L (10 micrograms/dL) or more in 20.5% and 0.97
      mumol/l (20 micrograms/dL) or more in 2.3% of children. Measurement of capillary
      blood lead levels performed very well as a screening test with an area under the
      ROC curve of 0.97 at the 0.48 mumol/L (10-micrograms/dL) threshold and 0.99 at
      the 0.97-mumol/L (20-micrograms/dL) threshold. For a capillary cutoff value of
      0.39 mumol/L (8 micrograms/dL) and an elevated blood lead level threshold of 0.48
      mumol/L (10 micrograms/dL), test sensitivity is 100% and the false-positive rate
      is 23%. Test sensitivity drops to 91%, 63%, and 45% at capillary cutoff values of
      0.48, 0.58, and 0.68 mumol/L (10, 12, and 14 micrograms/dL), respectively. The
      false-positive rate drops to 8%, 2%, and 1% at capillary cutoff values of 0.48,
      0.58, and 0.68 mumol/L (10, 12, and 14 micrograms/dL), respectively. Changing the
      contamination rate by appending or deleting contaminated capillary specimens from
      the data set had little effect on the area under the ROC curve at either
      threshold. CONCLUSIONS: In this sample of children, capillary blood lead
      measurement performed well as a screening test for elevated venous blood lead
      levels. Altering the capillary specimen contamination rate has little effect on
      the rest characteristics because much of the misclassification error resulted
      from random analytic error in the analysis of blood lead levels, which is high
      compared with the threshold of concern (0.48 mumol/L [10 micrograms/dL]). Because
      of lack of data on clinical outcomes for children with elevated blood lead levels
      in the 0.48- to 0.92-mumol/L (10- to 19-micrograms/dL) range, we suggest that the
      greatest utility be placed on avoiding false-positive misclassification. A
      clinical capillary screening cutoff value of 0.72 mumol/L (15 micrograms/dL)
      would avoid most false-positive results and would permit 100% sensitivity in
      detecting children with blood lead levels of 0.97 mumol/L (20 micrograms/dL) or
      higher.

PMID- 8859144
TI  - Effect of breakfast timing on the cognitive functions of elementary school
      students.
AB  - OBJECTIVE: To study the effect of breakfast timing on selected cognitive
      functions of elementary school students. DESIGN: A 2-week randomized control
      intervention trial. SETTING: Five elementary schools. SUBJECTS: The subjects
      comprised 569 children, 51% of them boys, aged 11 to 13 years; the children were
      in grades 5 through 6 (17 classes). The subjects lived in different areas and had
      different socioeconomic backgrounds. INTERVENTION: Each subject was tested twice,
      by 2 versions of the Rey Auditory-Verbal Learning Test, 2 alternative forms of
      the logical memory subtest of the revised Wechsler Memory Scale, and 2 versions
      of the Benton Visual Retention Test. On the first test, before any nutritional
      intervention, the subjects were asked to complete a questionnaire about their
      food intake on the day of testing. Two thirds of the subjects received 200 ml of
      3%-fat milk and 30 g of sugared cornflakes for the next 14 days, and all the
      subjects were reexamined on the 15th day. MAIN OUTCOME MEASURE: Scoring on the
      different tests was compared with baseline scores. RESULTS: After 15 days,
      children who ate breakfast at school scored notably higher on most of the test
      modules than did children who ate breakfast at home and children who did not at
      breakfast. CONCLUSIONS: Our results indicate that routinely eating breakfast 2
      hours prior to being tested does not improve cognitive functions in 11- to 13
      year-old elementary school students, but food supplementation 30 minutes prior to
      taking a test notably improves scoring. We suggest further studies on the
      relationship between meal content, feeding time, and scholastic performance.

PMID- 8859145
TI  - Injury prevention training in pediatric residency programs.
AB  - OBJECTIVES: To quantify the content and setting of injury prevention training
      provided to pediatric residents and to identify aspects of residency programs
      associated with this training. DESIGN: Mail survey. SETTING: US pediatric
      residency programs. PARTICIPANTS: Residency program directors. MAIN OUTCOME
      MEASURES: Number of programs stating that they train residents in various injury
      prevention topics, and the setting of this training. RESULTS: More than 80% of
      programs addressed 92% of topics surveyed dealing with disease prevention, but
      only 59% of topics dealing with injury prevention. Injury prevention topics
      covered less frequently included smoke detector use and swimming pool, sports,
      and firearm safety. Programs used continuity clinics most often to teach injury
      prevention. No specific program characteristic was associated with the content or
      setting of injury prevention training. Residency programs located in states in
      which house fires, drowning, or firearm injuries are the leading causes of death
      were not more likely to offer prevention training on these topics. CONCLUSIONS:
      Injury prevention is less frequently taught than disease prevention in pediatric
      residency training. Injury prevention is most often taught in continuity clinics,
      the setting most consistent with ongoing primary patient care. A gap exists
      between the leading causes of injury death and injury prevention topics taught to
      pediatric residents. Residency programs must better recognize and adapt to the
      epidemiology of trauma in their communities, better enabling new pediatricians to
      meet their patient's needs.

PMID- 8859146
TI  - Radiological case of the month. In utero ultrasonographic demonstration of a
      lymphangioma.

PMID- 8859147
TI  - Picture of the month. Transient primary hypothyroidism.

PMID- 8859148
TI  - Pathological case of the month. Congenital muscular torticollis.

PMID- 8859149
TI  - Pathological case of the month. Melanotic neuroectodermal tumor of infancy.

PMID- 8859150
TI  - The undoing of a diagnosis.

PMID- 8859151
TI  - False diagnosis of cystic fibrosis.

PMID- 8859152
TI  - The evolving role of fine needle cytology and core-biopsy in the diagnosis of
      breast cancer.

PMID- 8859153
TI  - The future of surgery in Papua New Guinea and the South Pacific.
AB  - Surgery in the South Pacific is different in many respects from surgery in
      Australia and New Zealand. It is primarily the surgery of trauma, infection,
      advanced malignancy, hollow-tube obstruction and congenital abnormalities.
      Specific tropical infections such as tuberculosis, typhoid, pigbel and amoebiasis
      occur regularly but constitute only a small proportion of all cases. The patients
      tend to be young, rural and poor, and often present late because access to
      surgical services is limited. The treatment patients receive is also compromised
      by a lack of resources--the result of underfunding and inefficient
      administration. Standards for appropriate surgical practice should be determined
      in-country and based at least on surgical audit and clinical studies. Even though
      Western diseases are emerging in the tropics, the best management may sometimes
      be different. Training of national surgeons is a priority if a sustainable
      surgical service is to be established. Such training is more effectively carried
      out in the home country, or at least in one with similar pathology and problems,
      rather than overseas. Project aid should support these schemes and encourage
      regional co-operation through the Fiji and Papua New Guinea medical schools.
      There remains an important role for visiting surgical specialists, but they need
      to ensure that they transfer skills and encourage the professional development of
      promising local doctors rather than simply focusing on treating patients.

PMID- 8859154
TI  - The management of large bowel obstruction.

PMID- 8859155
TI  - Stereotactic 14 gauge core-biopsy of the breast: results from 101 patients.
AB  - BACKGROUND: Along with fine needle aspiration (FNA) cytology, core-biopsy has
      become an integral part of the assessment of mammographically detected breast
      lesions. METHODS: A series of stereotactic large-core-biopsies of
      mammographically detected breast lesions was studied to assess the accuracy and
      limitations of the technique in diagnosing malignancy and in giving specific
      benign diagnoses, and its use in determining surgical management. RESULTS: Eighty
      per cent of carcinomas were diagnosed as malignant (absolute sensitivity). In
      88.8% of the cancers, the core-biopsy was classified as malignant, suspicious or
      atypical/indeterminate (complete sensitivity), and in 72% of the invasive
      carcinomas, invasive tumour was present in the core. The technique was more
      successful for invasive carcinomas than for ductal carcinoma in situ (DCIS)
      (absolute sensitivity 86.1 and 55.5, respectively; P = 0.28) and for malignant
      mass lesions than for a mass with associated microcalcifications or for pure
      microcalcifications (absolute sensitivity 91, 71 and 66.6%, respectively; P =
      0.19). In five of the 45 cancers (11.1%), no tumour tissue was present in the
      core, but all were excised after mammographic review and no delays in diagnosis
      have been experienced to date. The benign to malignant ratio for excised lesions
      was 0.11:1. Of the benign lesions, a specific diagnosis was given in 49%
      (calcifications in the core in a background of fibrocystic change, or
      postoperative scarring, or fibro-adenoma); the remainder showed non-specific
      benign findings. All patients where invasive carcinoma was diagnosed in the core
      underwent axillary clearance and wide local excision or mastectomy at their first
      operation. CONCLUSIONS: This technique can markedly reduce the number of benign
      lesions needing open biopsy, and provide information allowing definitive
      management of most carcinomas at the first operation. The accuracy of core-biopsy
      was lower in DCIS/microcalcification lesions; extra core samples or a combination
      of FNA and core-biopsy may be of value in these cases.

PMID- 8859156
TI  - Diagnosis of breast cancer with core-biopsy and fine needle aspiration cytology.
AB  - BACKGROUND: Patients who are elderly or who have locally advanced breast cancer
      may initially receive primary medical therapy. METHODS: In order to avoid open
      biopsy in such patients, we routinely perform both fine needle aspiration
      cytology (FNAC) and core-biopsy at the first clinic visit. RESULTS: A
      retrospective review showed that of 109 such patients, 87 (80%) had the diagnosis
      confirmed on FNAC and 96 (88%) on core-biopsy. Only eight patients did not have a
      diagnostic result from the first clinic visit, and five of these patients were
      diagnosed on a repeat core-biopsy or FNAC. The remaining three patients had
      suspicious FNAC. Overall 97% had one or both investigations positive.
      CONCLUSIONS: When considered alone core-biopsy was superior to FNAC. In this
      series the combined diagnostic approach of FNAC and core-biopsy has allowed
      outpatient diagnosis for virtually all patients.

PMID- 8859157
TI  - Stereotactic fine needle aspiration in the management of mammographic
      abnormalities detected in breast screening.
AB  - BACKGROUND: Fine needle aspiration (FNA) is used routinely in the management of
      palpable breast lumps; with the implementation of the stereotactic technique its
      use has been extended to the investigation of mammographic abnormalities. The
      advent of breast screening means that many mammographic abnormalities will be
      detected; because routine open biopsy is impractical and undesirable,
      stereotactic fine needle aspiration becomes the method of choice for
      investigation. METHOD: Within a 28 month interval, 81 Chinese women underwent
      stereotactic FNA in Kwong Wah Hospital, Hong Kong. RESULTS: Fifty-one women
      (62.9%) had a benign cytology result and no further investigations were required.
      Inconclusive results were obtained in 18.6% of the aspirates. Open biopsy was
      required in 16 women (19.8%). CONCLUSION: Stereotactic FNA is very useful in the
      exclusion of malignancy and the avoidance of open biopsy in asymptomatic women
      who have mammographic abnormalities.

PMID- 8859158
TI  - A prospective study on the use of water-soluble contrast follow-through radiology
      in the management of small bowel obstruction.
AB  - BACKGROUND: The purpose of this prospective study was to determine the value of
      water-soluble contrast follow-through radiology in predicting the outcome in
      patients with small bowel obstruction. METHODS: Patients with clinical and
      radiological evidence of small bowel obstruction were selected according to pre
      set criteria. A water-soluble contrast follow-through examination using 76%
      urografin was carried out within 24 h of hospital admission. The result was
      interpreted as 'significant obstruction' if the contrast failed to reach the
      caecum in 4 h or if there was a clear cut-off in the gastrointestinal tract. The
      result was interpreted as 'insignificant obstruction' if the contrast reached the
      caecum within 4 h. The surgeon was blinded to the result of the contrast
      examination in the patient management, and the decision to operate was based
      entirely on conventional clinical grounds. RESULTS: Fifty-one patients in an 18
      month period underwent the contrast examinations. Thirty-four patients (67%) had
      previous abdominal operations. The results showed that significantly more
      patients who had 'significant obstruction' on contrast radiology required surgery
      to relieve the intestinal obstruction (17/19) than those who had "insignificant
      obstruction' (1/32; Fisher's exact test, P < 0.0001). This difference was found
      to be significant in both patient subgroups: patients with or without previous
      abdominal operation. There was no major morbidity or mortality related to the
      contrast radiology procedure. CONCLUSIONS: Urografin follow-through examination
      is a safe procedure; using 4 h as the cut-off it is highly predictive of the
      outcome in small bowel obstruction in patients with or without previous abdominal
      operation.

PMID- 8859159
TI  - The management of left-sided large bowel obstruction: an audit.
AB  - BACKGROUND: The outcomes of patients admitted acutely to hospital with left-sided
      large bowel obstruction (LBO) were examined. METHODS: All patients admitted to
      the colorectal service (University Department of Surgery, Wellington School of
      Medicine) with LBO between 1975 and 1990 were reviewed. Sixty-four patients with
      left-sided LBO were identified. RESULTS: The most commonly found obstructing
      lesion was cancer. Two patients were not managed surgically. In 17.7% of patients
      there was development of postoperative respiratory complications and 16%
      developed wound problems following primary surgery. Fifty-nine patients survived
      their primary surgery and 45 had stomas. The stoma closure rate was 71.1% (32 of
      45). The overall mortality rate for patients managed surgically was 6.5% (four of
      62). The mortality rate for stoma formation was 4.3% (two of 47). The mortality
      rate for resection and then stoma closure was 3.2% (one of 32). CONCLUSIONS: This
      study has shown that a staged approach to the management of unselected patients
      with left-sided LBO is safe. Restoration of bowel continuity was achieved in 70%
      of patients.

PMID- 8859160
TI  - Lymphovascular clearance in laparoscopically assisted right hemicolectomy is
      similar to open surgery.
AB  - BACKGROUND: The application of laparoscopic techniques to malignant colorectal
      disease has led to concerns regarding the adequacy of excision achieved. This
      study was performed to compare specimen histopathology following laparoscopically
      assisted right hemicolectomy (LARHC) with that following open right hemicolectomy
      (ORHC). METHODS: Data regarding patient details and tumour pathology were
      obtained by case-note review and from the Concord Hospital Colorectal Cancer
      Database. Thirty-two patients had LARHC for neoplastic lesions and 34 had ORHC
      for similar lesions over the same period. The two groups were well matched with
      respect to age, sex, weight and tumour characteristics. Early stage disease was
      more common in the LARHC group. RESULTS: There was no clinically significant
      difference between the groups in terms of margins of clearance or number of lymph
      nodes harvested. CONCLUSIONS: LARHC allows lymphovascular clearance
      indistinguishable from that afforded by open surgery. Long term outcome and
      survival data are required to confirm its role in the treatment of malignant
      colorectal disease.

PMID- 8859162
TI  - The genitofemoral nerve may link testicular inguinoscrotal descent with
      congenital inguinal hernia.
AB  - The genitofemoral nerve (GFN) hypothesis for inguinoscrotal testicular descent
      proposes that calcitonin gene-related peptide (CGRP), released from the
      genitofemoral nerve, controls the migration of the gubernaculum from the inguinal
      region to the scrotum between 26 and 40 weeks of gestation. The processus
      vaginalis provides a channel through which the testis descends from the abdomen
      to the scrotum. Following descent of the testis the processus vaginalis undergoes
      luminal obliteration and disappearance between the internal inguinal ring and the
      upper pole of the testis. The mechanism underlying closure of the processus is
      unknown and failure for it to occur normally results in congenital inguinal
      hernia, scrotal hydrocele and possibly even an 'ascending' testis. Recent work in
      our laboratory suggests that CGRP, released from the genitofemoral nerve, may
      cause fusion and disappearance of the processus vaginalis. We propose that
      abnormalities in the GFN link a spectrum of disorders encompassing congenital
      undescended testis, inguinal hernia, scrotal hydrocele and ascending testis.

PMID- 8859161
TI  - Internal pancreatic fistulae with serous effusions in chronic pancreatitis.
AB  - BACKGROUND: Serous effusions in chronic pancreatitis are infrequent but
      persistent. These occur usually as a consequence of internal pancreatic fistulae
      and commonly involve the pleural cavity or peritoneum. METHODS: To assess
      strategies in operative management, the records of 12 patients who underwent
      surgery for internal pancreatic fistula with underlying chronic pancreatitis were
      reviewed retrospectively. Seven patients had pancreatic ductal calculi. Three
      cases underwent external drainage. Three cases with leaking pseudocysts underwent
      cystojejunostomy-en-Y. Three cases with ductal dilatation or calculi underwent
      lateral pancreaticojejunostomy and three patients had caudal pancreatectomy for
      distal disease. RESULTS: Eight patients were completely controlled of all
      symptoms, with no sequelae. One case each had recurrent pancreatitis and ascites
      but did not require re-operation. There were two deaths: one with massive
      haematemesis and one with pre-existent multi-organ failure and sepsis.
      CONCLUSIONS: Pancreatic duct stones may be causally associated with internal
      pancreatic fistulae. Delineation of ductal anatomy and pathological aberrations
      of the pancreas, including determination of the leak site, was of paramount
      importance in planning surgery. Peroperative ductography proved the most useful
      in this regard.

PMID- 8859163
TI  - Duplex scanning for recurrent varicose veins.
AB  - BACKGROUND: Most studies of recurrent varicose veins have been based on the
      findings clinically, at operation, or on phlebography. Occasionally these
      findings have been compared with Doppler findings produced by hand-held
      continuous-wave Doppler. Duplex scanning is a more refined approach to the
      assessment of recurrent varicose veins. METHODS: 202 patients (267 legs) have
      been examined consecutively for recurrent varicose veins between January 1990 and
      December 1995 at St George Vascular Laboratory. This was a retrospective study of
      some aspects and patterns of recurrence of varicose veins in this group. RESULTS:
      The ratio of female to male was 3:1. The mean age of the group was 52 years and
      mean time to recurrence was 13 years (1 year 95% CI). There were six patterns of
      recurrence accounting for 95.2% of legs. In descending order of frequency, these
      were: (i) the saphenofemoral junction and long saphenous vein were intact and
      incompetent (44.6%); (ii) an incompetent thigh perforator and long saphenous vein
      remained intact; there was no saphenofemoral junction (16.5%); (iii) the long
      saphenous vein remained intact and incompetent; there was no saphenofemoral
      junction (10.5%); (iv) there was an incompetent saphenofemoral junction only
      (9.74%); (v) there was an intact and incompetent saphenopopliteal junction alone
      (9.74%); and (vi) an isolated thigh perforator was incompetent, with no more
      proximal site of incompetence detected (4.12%). Incompetent calf perforator
      (69.2%) and gastrocnemius veins (9.3%) were frequently detected, but rarely
      existed in isolation (seven legs in total). CONCLUSIONS: Duplex scanning is an
      important recent adjunct to the management of recurrent varicose veins in order
      to define the pathway of incompetence'. The saphenofemoral junction and long
      saphenous vein remain the key to recurrence of varicose veins. Calf perforator
      and gastrocnemius vein incompetence are of secondary importance in recurrent
      varicose veins.

PMID- 8859164
TI  - A self-expanding endoluminal graft for treatment of aneurysms: results through
      the development phase.
AB  - BACKGROUND: The results of two and a half years' experience of endoluminal
      treatment of aneurysmal disease (from March 1993 to December 1995) are reported.
      METHODS: The endoluminal grafts were individually made at Royal Perth Hospital.
      They are based on Dacron-covered stainless steel self-expanding 'Z' stents with
      Gianturco barbed stents (Cook Pty, Australia) for proximal anchorage for grafts
      within the aorta. RESULTS: Fourteen straight tube grafts (nine for aortic
      aneurysm, four for iliac aneurysm and one for subclavian aneurysm) and 24
      bifurcate grafts were deployed; all were in patients considered high-risk for
      conventional repair. Seventy-two per cent of the straight tube grafts
      successfully excluded the aneurysm. The bifurcate grafts, in use since July 1994,
      successfully excluded the aneurysm in 88%. There were two delayed deaths from
      rupture after the grafts failed to exclude the aneurysms; two patients required
      conversion to open repair and survived; three patients have persistent endoleaks;
      and three of the bifurcate grafts subsequently occluded a graft limb but did not
      require further intervention. Ninety per cent of these complications occurred in
      the first half of the series (prior to January 1995). CONCLUSIONS: A learning and
      development curve was clearly apparent. The results thereafter compare favourably
      to those for open repair in similar high-risk groups, suggesting that these
      techniques hold promise for all patients with aneurysms.

PMID- 8859165
TI  - Issues in anatomy: the external anal sphincter revisited.
AB  - Textbooks of anatomy often fail to reflect controversies or new developments in
      anatomy. This impinges on the conduct of examinations in anatomy with respect to
      whether the correct answer is what appears in the textbook or what is known in
      the research literature. The example of the external anal sphincter is addressed.
      Whereas textbooks portray this muscle as having three, essentially circular
      parts, past and more recent work denies this description. Rather, the sphincter
      consists of three loops; one formed by puborectalis, one stemming from the coccyx
      and one stemming from the pre-anal skin. Surgeons in training should recognise
      that anatomy is not a static science and that idealized descriptions that occur
      in textbooks do not necessarily reflect actual anatomy or controversies about it.

PMID- 8859166
TI  - The portrayal of the doctor in non-medical literature. 15. The surgeon.
AB  - Fictional surgeons are perceived as confident and competent individuals. They may
      not have a profound knowledge of basic physiology or statistical methods and
      their social behavior may lack refinement, but they are great technologists and
      most of their patients get better. Inside the operating room, surgeons are
      absolute autocrats, with a few abusing their position and turning into petty
      tyrants. The prominent status of fictional surgeons within the medical profession
      is reflected in their arrogant and patronizing attitudes towards patients,
      primary care doctors and non-surgical specialists. Fictional surgeons are
      impatient, irascible and aggressive. These traits make them poor communicators
      and teachers. A few are suspected of harbouring sadistic tendencies. On the other
      hand, when the surgeon turns his aggression towards the disease process rather
      than his colleagues or his trainees, it enables him to achieve some spectacular
      therapeutic successes.

PMID- 8859167
TI  - Sarcomatoid carcinoma of the small intestine.
AB  - A case of sarcomatoid carcinoma of the small intestine in a 76 year old Chinese
      woman is presented. The diagnosis was confirmed by light microscopic,
      immunohistochemical and ultrastructural findings. It is a rare neoplasm, with
      only 13 previous reported cases in the literature. Patients with the disease
      usually had a poor prognosis. The nomenclature, histological and
      immunohistochemical findings of these tumours were diverse. To our knowledge,
      this case is the first report of this disease entity in a Chinese patient, and
      has its distinctive features. The patient was the oldest one in literature with
      this disease, and had the shortest survival time after the presentation of
      symptoms.

PMID- 8859168
TI  - A mobile lesion in the carotid artery.
AB  - The case of a 68 year old woman with a sudden onset of visual loss in the left
      eye is reported. Carotid duplex scanning revealed a 50-75% stenosis of the left
      internal carotid artery, with a floating tail of clot extending into the lumen of
      the artery. Emergency carotid endarterectomy, removing the plaque with the
      attached thrombus, was performed.

PMID- 8859169
TI  - Ileostomy dysfunction with adjuvant chemoradiation for rectal carcinoma requiring
      in-hospital management: a cause for concern.
AB  - The morbidity and mortality of 20 patients undergoing adjuvant chemoradiation for
      rectal carcinoma was documented. Of nine patients with defunctioning loop
      ileostomies, two suffered from dehydration and electrolyte disturbance during the
      treatment phase and required admission to hospital. These two cases suggest that
      dehydration and electrolyte disturbance from high stomal output could be a
      serious problem following chemoradiation therapy in patients with an ileostomy.

PMID- 8859170
TI  - Xanthogranulomatous inflammation of the sigmoid colon: a case report.
AB  - A rare case of xanthogranulomatous inflammation of the sigmoid colon presenting
      as intestinal obstruction is reported. This is the first report of this lesion
      involving the large bowel which demonstrated the characteristic macroscopic and
      microscopic features. Though rare, xanthogranulomatous inflammation should be
      considered in patients presenting with large bowel obstruction.

PMID- 8859171
TI  - False aneurysm of the popliteal artery complicating acupuncture.
AB  - This is the first reported case in which acupuncture needle injury of the
      popliteal artery caused the development of a false aneurysm. The patient
      presented with rupture of the aneurysm and was successfully managed by arterial
      repair.

PMID- 8859172
TI  - 'Idiopathic' chronic gastric volvulus.
AB  - Gastric volvulus usually occurs secondary to another condition such as hiatal
      hernia. We report a case of so-called "idiopathic' gastric volvulus where the
      only abnormality was laxity of the gastric attachments. Upper gastrointestinal
      endoscopy was unhelpful in making the diagnosis, but a barium meal clearly
      demonstrated the abnormality. The patient underwent a Polya gastrectomy with a
      retrocolic gastroenterostomy, which was thought to be the best method of ensuring
      gastric fixation.

PMID- 8859173
TI  - Recurrent pyogenic cholangitis or "oriental cholangiohepatitis' in occidentals:
      case reports of four patients.
AB  - The first description of recurrent pyogenic cholangitis occurring in four
      occidentals is presented. While recurrent pyogenic cholangitis is a common
      syndrome of uncertain aetiology among orientals (also known as oriental
      cholangiohepatitis), it has not previously been described in occidentals. Four
      such patients are described. They presented with recurrent attacks of ascending
      cholangitis and associated hepatolithiasis, biliary stricturing and dilation.
      Focal hepatic involvement was treated by segmental liver resection and recurrent
      disease by interventional endoscopy or radiology.

PMID- 8859174
TI  - Regional versus systemic chemotherapy in the treatment of colorectal carcinoma
      metastatic to the liver. Is there a survival difference? Meta-analysis of the
      published literature.
AB  - BACKGROUND: A number of articles have appeared in the medical literature
      regarding regional infusion chemotherapy for the treatment of metastatic
      colorectal carcinoma confined to the liver. The results and conclusions have been
      varied. A meta-analysis of the literature was undertaken to determine if regional
      infusion chemotherapy using either 5-fluorouracil or floxuridine (FUDR) confers a
      survival advantage over systemic chemotherapy for the treatment of this disease.
      METHODS: A MEDLINE search was conducted encompassing the period from January 1976
      to May 1995. The search was narrowed to include only articles that referenced
      prospective randomized clinical trials. A total of 149 articles or abstracts were
      reviewed for potential eligibility in this meta-analysis. Six articles met the
      current study inclusion criteria. One and 2-year survival rates for each
      treatment modality were directly retrieved from each study or calculated from the
      Kaplan-Meier survival curves that were presented. Prior to pooling the estimates
      of the treatment survival differences, a test was conducted for homogeneity of
      the treatment effect using the test statistic proposed by DerSimonian and Laird
      1986. The fixed effect model was then used to obtain summary estimates of the
      survival differences from the group of studies. RESULTS: Regional infusion
      chemotherapy with FUDR produced a 10% (P = 0.041) and 6% (P = 0.124) increased
      survival at 1 and 2 years, respectively. CONCLUSIONS: Based on this meta
      analysis, it appears that hepatic artery infusion chemotherapy confers a modest
      survival benefit over systemic chemotherapy. Whether this is clinically relevant
      depends on the quality rather than just the duration of survival.

PMID- 8859175
TI  - Effective radiochemotherapy with cisplatin and etoposide for the management of
      patients with locally inoperable and metastatic esophageal carcinoma.
AB  - BACKGROUND: The limited therapeutic value of available chemotherapeutic drug
      combinations in patients with advanced esophageal carcinoma, the documented
      synergistic activity of etoposide and cisplatin, which might be further enhanced
      by simultaneous radiotherapy, and promising though only preliminary therapeutic
      results with this combination regimen have stimulated the present Phase II trial.
      The specific aim of the study was to determine the efficacy and tolerance of this
      combined treatment approach in previously untreated patients with either local
      regional unresectable or metastatic esophageal carcinoma. METHODS: Thirty
      patients with Stage IIIB or IV squamous cell or adenocarcinoma of the esophagus
      were entered in this study between October 1992 and November 1994. Chemotherapy
      was comprised of cisplatin, 30 mg/m2, combined with etoposide, 120 mg/m2, both
      given intravenously on 4 consecutive days. Treatment courses were repeated every
      4 weeks. Radiation therapy (total dose, 5000 centigray) was administered
      concurrently during the 2nd and 3rd chemotherapy course, during which both drugs
      were given with a 25% dose reduction. RESULTS: After a median of 4
      chemotherapeutic treatment courses (range, 1 to 6 courses), 3 patients had a
      complete response for 5, 8, and 11.5 months, and 9 patients had a partial
      response lasting for a median duration of 5.3 months (range, 2.5 to 7.5 months),
      yielding an overall response rate of 40% (95% confidence interval, 23-59%). The
      response rates tended to be higher for squamous cell carcinomas (11 of 23; 48%)
      than for adenocarcinomas (1 of 7), as well as for locoregional disease (7 of 13;
      54%) than for patients with disseminated disease (5 of 17; 29%). For the entire
      study population, median time to progression was 5.4 months (range, 1.5 to 13.5
      months), and median survival was 9.2 months (range, 1.5 to 28 months), with 4
      patients still alive at the time of this report. Clinically, the most important
      toxic effect was myelosuppression. Grade 3-4 granulocytopenia occurred in 16
      patients (53%), severe thrombocytopenia in 11 (37%), and Grade 3 anemia in 5
      (17%). There were four hospitalizations among three patients for the management
      of fever during neutropenia. Other nonhematologic side effects were generally
      mild or modest, and most commonly included nausea/emesis (40%), mucositis and/or
      esophagitis during simultaneous radiotherapy (40%), and alopecia (43%).
      CONCLUSIONS: Combined radiochemotherapy with cisplatin and etoposide is active
      against advanced esophageal carcinoma, but can be associated with significant
      hematotoxicity. Although the therapeutic potential of this regimen appears to be
      comparable to other, conventional fluorouracil/cisplatin-based chemotherapy, less
      toxic and more effective regimens need to be identified.

PMID- 8859176
TI  - Gastrointestinal autonomic nerve tumor of the esophagus. A clinicopathologic,
      immunohistochemical, ultrastructural study of a case and review of the
      literature.
AB  - BACKGROUND: Gastrointestinal autonomic nerve (GAN) tumor is a rare tumor that is
      supposed to originate from the enteric autonomic plexus. The tumor is a subgroup
      of the gastrointestinal stromal tumor that usually occurs in the stomach and
      small intestine. METHODS: An intramural tumor located in the upper third of the
      esophagus of a 62-year-old Chinese female is reported. The tumor was removed by a
      three-phased esophagogastrectomy because of its large size. The tumor measured
      6.5 cm x 5 cm x 4 cm. Its tissues were sampled, examined by light microscopy,
      immunohistochemistry, and electron microscopy. RESULTS: The tumor was vaguely
      encapsulated but had foci of partial infiltration of the capsule. It was
      comprised of spindle cells with moderate nuclear pleomorphism. The mitotic count
      was less than 1 per 10 high-power field. The tumor stained positive for vimentin,
      neuron specific enolase (NSE), and S-100 protein, and was negative for
      cytokeratins, synaptophysin, chromogranin, neurofilaments, muscle markers, HMB45,
      and CD34. Ultrastructural study revealed that the tumor had cytoplasmic processes
      interdigitated in a complex fashion that were held together by primitive
      junctions but not invested in basal lamina. Many neurosecretory granules and
      neurotubules were also noted. The diagnosis was GAN tumor of the esophagus. From
      previous reports, 43 cases (25 males, 18 females) of GAN tumor of other locations
      have been documented. The tumors were located almost exclusively in the stomach
      and small intestine; rare cases arose primarily in the retroperitoneum and
      mesentery. Some of these GAN tumors were observed in patients with Carney's triad
      (three cases), neurofibromatosis (two cases), and adrenal ganglioneuroma (one
      case). It appears that the biologic behavior of GAN tumors is aggressive but
      there are too few reports on which to conclude anything about their prognosis.
      The tumors are usually large, with low mitotic rate, and are positive for NSE and
      negative for muscle markers. CONCLUSIONS: To the authors' knowledge, this is the
      first time that GAN is described in the esophagus. The diagnosis can be made only
      on the basis of characteristic ultrastructural features.

PMID- 8859177
TI  - Effect of indomethacin suppositories on rectal polyposis in patients with
      familial adenomatous polyposis.
AB  - BACKGROUND: Oral sulindac is known to reduce polyps in patients with familial
      adenomatous polyposis (FAP). The authors speculated that rectal administration of
      indomethacin would be effective therapy for adenomas in the rectal remnant of
      FAP. METHODS: Eight patients with FAP who had been treated by total colectomy
      with ileorectal anastomosis were administered an indomethacin suppository (50 mg)
      once or twice daily during a period of 4 or 8 weeks. The number of polyps at the
      same site within the rectum was counted under proctoscopy prior to, at the end
      of, and after the treatment. In four patients, proliferative activity of the
      rectal mucosa was assessed by immunohistochemical staining for MIB-1. RESULTS: In
      six of the eight patients who initially had ten or more polyps, the number of
      polyps decreased to fewer than five, whereas such a decrease could not be
      observed in the remaining two patients. In the six patients, the number of polyps
      increased after indomethacin was discontinued. The proliferative activity of the
      rectal mucosa was higher at the end of treatment than it was prior to
      indomethacin administration. CONCLUSIONS: Indomethacin suppositories may be
      effective in the management of rectal adenomatosis in patients with FAP.

PMID- 8859178
TI  - A description of age, sex, and site distributions of colon carcinoma in three
      geographic areas.
AB  - BACKGROUND: Site of the carcinoma within the colon in relation to age and sex may
      provide clues into the etiology of the disease. Incidence of colon carcinoma by
      age, sex, and tumor site at a population-based level are reported infrequently.
      The goal of this study was to describe the distribution of colon carcinoma
      (excluding cancers of the rectosigmoid junction and rectum) by age at diagnosis,
      sex, and site of the tumor within the colon. These factors were also evaluated in
      conjunction with disease stage at the time of diagnosis. METHODS: Data from three
      geographically distinct populations were used to describe rates of colon
      carcinoma and the distribution of tumors by age, tumor site, and stage at
      diagnosis. All colon carcinoma cases diagnosed within a 3-year period within the
      areas are included. RESULTS: Approximately 50% of all cancers in men and greater
      than 50% of cancers in women were in the proximal segment of the colon. Men who
      were diagnosed prior to age 50 and both men and women diagnosed at age 70 or
      older had predominantly proximal cancers. People with proximal cancers and people
      diagnosed prior to age 50 were more likely to have more advanced disease.
      CONCLUSIONS: Both men and women have more proximal cancers with advancing age,
      which are associated with more advanced disease. Observed trends in cancer site
      distributions could reflect screening practices, environmental and genetic
      factors, or a combination of these variables.

PMID- 8859180
TI  - Functional expression of CD11a on CD8+ cells is suppressed in regional lymph
      nodes with cancer involvement in patients with gastrointestinal carcinoma.
AB  - BACKGROUND: To evaluate the immunologic activity of regional lymph nodes, the
      phenotype of lymphocytes and the functional expression of cell adhesion molecules
      (CAMs) on lymph node lymphocytes (LNL-: uninvolved, LNL+: involved) were
      investigated in patients with gastrointestinal carcinoma. METHODS: The lymphocyte
      subpopulation and the expression of CD11a, CD44, and CD29 on CD4+ and CD8+ cells
      in peripheral blood lymphocytes (PBL), LNL- and LNL+ derived from 37 patients
      with gastrointestinal carcinoma were studied. In addition, the adherence of CD8+
      cells to ICAM-1 which reflects the adhesive function of CD11a, was examined, and
      changes in this adherence were studied by experimental coculture with cancer
      cells (DLD-1). RESULTS: Although there were no differences in the overall
      proportion of T cells between the groups, CD8+ cells and CD16+ cells were
      considerably diminished in LNL+. The expression of CD11a and CD29 on CD4+ and
      CD8+ cells was significantly lower in LNL than in PBL, whereas the expression of
      CD44 showed no significant differences. The expression levels of these CAMs were
      almost the same in LNL- and LNL+. Only CD11a expression on CD8+ cells in LNL+ was
      significantly lower than that in LNL- (P < 0.005). The adherence of CD8+ cells in
      LNL+ to ICAM-1 was lower than that in PBL and LNL-, and was extremely enhanced by
      experimental coculture with cancer cells (DLD-1). CONCLUSIONS: These data
      indicate that the functional expression of CD11a (LFA-1) on CD8+ T cells is
      suppressed in cancer-involved regional lymph nodes in patients with
      gastrointestinal carcinoma.

PMID- 8859179
TI  - Surgical treatment of patients with mixed hepatocellular carcinoma and
      cholangiocarcinoma.
AB  - BACKGROUND: The results of treatment of mixed hepatocellular carcinoma (HCC) and
      cholangiocarcinoma (CC) remain unclear because of the rarity of this disease.
      METHODS: Of 218 patients with primary liver carcinoma treated from 1979 to 1995,
      6 had a histologic diagnosis of mixed HCC and CC (MHC). Five had chronic liver
      disease. Serum carcinoembryonic antigen (CEA), CA 19-9, and alpha-fetoprotein
      (AFP) levels were determined and hepatic angiography was performed
      preoperatively. Left trisegmentectomy (with portal vein reconstruction) and
      extended right lobectomy were performed in one patient each, whereas selective
      subsegmentectomy was done in three patients, and partial resection of segment 3
      in one patient. Hilar lymphadenectomy was performed in two patients. RESULTS:
      Mild liver dysfunction was observed in two patients. The resected tumors ranged
      from 2.7 to 12 cm in size and all showed intermingling of HCC and CC elements. A
      preoperative diagnosis of MHC was possible in one patient because of a high AFP
      level and hypovascularity, whereas a high CEA level and hypervascularity led to
      the diagnosis in another patient. High levels of AFP, CEA, and CA 19-9 were
      observed in three, one, and three patients, respectively. There were no
      metastases in the dissected lymph nodes. Although 2 patients had died by 2 years
      after surgery, the 5-year survival rate was 60% and there were 2 long term
      survivors for more than 10 years. CONCLUSIONS: A hypervascular tumor with high
      CEA and CA 19-9 levels or a hypovascular tumor with a high AFP level may suggest
      a preoperative diagnosis of MHC in patients with suspected HCC. Extensive surgery
      is an effective treatment for this disease, except in patients with satellite
      nodules. Hilar lymphadenectomy may not be necessary in selected patients.

PMID- 8859181
TI  - Peritoneal carcinomatosis in patients with digestive endocrine tumors.
AB  - BACKGROUND: Peritoneal carcinomatosis (PC) in patients with digestive endocrine
      tumors (DET) is considered rare but its prevalence is unknown. The objectives of
      this study were to assess the prevalence and prognostic implications of PC in
      patients with various types of DET. METHODS: One hundred and sixteen consecutive
      patients with DET seen over a 3-year period were studied. Fifty-nine had
      gastrinomas, 30 had carcinoid tumors, and 27 had other types of endocrine tumors,
      mainly nonfunctioning ones. Diagnosis of PC was based on clinical symptoms
      (ascites and Konig's syndrome), findings of computed tomography scans that were
      performed at least yearly, and pathologic confirmation of tumor nodules or
      positive cytology in the peritoneal fluid. Factors associated with PC were
      investigated and the influence of PC on patients' survival was assessed. RESULTS:
      PC was found in 11 patients (overall PC prevalence: 10%; with 27% in patients
      with carcinoid tumors, 11% in those with nongastrinoma pancreatic endocrine
      tumors, and 0% in patients with gastrinomas). Nine of 11 patients with PC also
      had liver metastases. PC was metachronous to detection of the primary tumor in 7
      of 11 patients, occurring 54 months (range, 23-273 months) after the diagnosis.
      In addition to the nature of the primary tumor, a greatest dimension of more than
      5 cm was associated with the presence of PC in two of three patients with
      pancreatic endocrine tumors. In patients with carcinoid tumors, an ileal primary
      tumor occurred more frequently in patients with PC (87.5%) than in those without
      PC (50%). Prevalence of liver and other metastases was not significantly
      increased in patients with PC. Although five patients died of their disease, no
      deaths were related to PC. Actuarial survival rates at 5 years were 64% and 84%
      in patients with and without PC, respectively (P = not significant), whereas they
      were 73% and 93% in patients with and without liver metastases, respectively (P <
      0.02). CONCLUSIONS: PC is not a rare event in the course of DET, especially in
      patients with carcinoid tumors. It did not occur in the patient population with
      gastrinomas, which are less often malignant but may also differ from the other
      types of DET by several cell characteristics. In contrast to liver metastases, PC
      is not associated with a significant decrease in life expectancy.

PMID- 8859182
TI  - Prognostic significance of clinical factors and p53 expression in patients with
      glottic carcinoma treated with radiation therapy.
AB  - BACKGROUND: Numerous clinical parameters have been suggested as predictors of
      outcome for patients with head and neck carcinoma treated with radiation therapy,
      but their applicability remains controversial. Inactivation of the p53 tumor
      suppressor results in radioresistance in experimental systems and might predict
      treatment failure in human patients. We have tested this hypothesis by comparing
      the predictive power of nuclear accumulation of p53 protein with that of clinical
      and histopathologic markers in patients with glottic carcinoma treated with
      primary radiotherapy. METHODS: Clinical charts were reviewed for 165 patients
      with glottic squamous cell carcinoma treated with radiation therapy. One hundred
      and twenty-one patients with T1 or T2 classified tumors were determined to have
      received adequate treatment and to have adequate follow-up data for further
      study. Archival pretreatment tumor biopsies from a subpopulation of patients were
      examined for p53 protein by immunohistochemistry. The influence of clinical and
      histopathologic variables and p53 nuclear protein on tumor recurrence was studied
      by bivariate and multivariate analysis. RESULTS: The recurrence rate was lowest
      for patients with moderately to poorly differentiated tumors (P < 0.05). This was
      the only significant predictor of outcome in this patient population. The
      presence of immunohistochemically detectable p53 antigen was not predictive of
      tumor recurrence in 70 patients for whom there was both p53 and sufficient follow
      up data. CONCLUSIONS: Histologic differentiation was prognostic for tumor
      recurrence in this population of patients with glottic carcinoma treated with
      radiation therapy. In contrast, nuclear accumulation of p53 protein was not
      predictive of tumor response or recurrence in this population.

PMID- 8859183
TI  - Mitomycin C, vinblastine, and carboplatin regimen in patients with nonsmall cell
      lung cancer. A phase II trial.
AB  - BACKGROUND: The mitomycin C, vinblastine, and cisplatin (MVP) combination is one
      of the most frequently used in the palliative setting, but it produces
      considerable toxicity. Carboplatin and cisplatin have different patterns of
      toxicity. The goal of this study was to evaluate a combination similar to MVP,
      using carboplatin instead of cisplatin to render it more feasible in an
      outpatient setting. METHODS: Inclusion criteria for this study included:
      inoperable patients or patients relapsing after previous surgery, with nonsmall
      cell lung carcinoma (NSCLC), a performance status (PS) > 50%, and no previous
      chemotherapy. The chemotherapy regimen included carboplatin, 300 mg/m2 on Day 1;
      mitomycin, 8 mg/m2 on Day 1; and vinblastine, 4 mg/m2 on Days 1, 8, and 15 (on
      Day 15 vinblastine was delivered only in the first cycle) (MVC) every 3 weeks for
      at least 3 cycles. RESULTS: From August 1991 until August 1994, 70 patients
      entered the trial. All were evaluable for toxicity and response. The median age
      was 62 years (range, 40-73 years). The male/female ratio was 60:10 (86%:14%); the
      ratio of Stage III to Stage IV disease was 26:44 (37%:63%); and the ratio of PS >
      70 to < or = 70 was 49:21. A total of 296 cycles (median, 4 [range, 1-6 cycles]
      per patient) were delivered, 280 of 296 (95%) in an outpatient setting with only
      4 patients requiring hospitalization for treatment delivery. Overall response
      rate (RR) was 38.6% (95% confidence interval [CI], 27-51%) (1 complete response,
      1.5%; 26 partial responses, 37.1%). Median duration of response was 9.8 months
      (range, 2-27 months). In Stage III patients the RR was 42% and in Stage IV
      patients it was 34%. Overall median survival was 9.5 months (95% CI, 6.8-15.3
      months). Survival at 1 year was 39% (standard error [SE] 3.6%) and was 11% at 2
      years (SE 3.6%). In Stage III patients median survival was 13 months and the 1
      year survival rate was 54% (SE 10%); Stage IV patients had a median survival of
      7.4 months and a 1-year survival rate of 28% (SE 7%). Delivered dose intensity
      was: carboplatin, 71%; vinblastine, 60%; and mitomycin C, 77% of the planned dose
      intensity. The back calculation of carboplatin area under the curve (AUC) with
      Calvert's formula and with the Cockcroft-Gault glomerular filtration rate
      estimation, showed a median AUC value of 4 (range, 2-8). Using the more precise
      Chatelut formula, AUC was again 4 (range, 2-7). Hematologic toxicity was the
      major side effect; Grades 3 and 4 leukopenia were observed in 34% and 6% of
      patients, respectively, and Grades 3 and 4 thrombocytopenia in 25% and 4% of
      patients, respectively. Grade 2 infection occurred in 10% of patients, with only
      1 case of sepsis; severe constipation and Grade 2 alopecia occurred in only 1
      patient; and no case of higher than Grade 1 nephrotoxicity was observed. No
      pulmonary toxicity was observed. Compliance with treatment was good with only one
      patient refusal after the first cycle. CONCLUSIONS: Chemotherapy for advanced
      NSCLS is still controversial, because effectiveness in terms of RR and symptom
      control must be weighed against treatment toxicity and costs. From our study it
      appears that MVC is easy to deliver in an outpatient setting, and has good
      patient compliance, low toxicity profile, and promising RR and response duration.
      The substitution of carboplatin for cisplatin in regimens for advanced NSCLC
      should be considered.

PMID- 8859184
TI  - The effect of patient and physician reminders on use of screening mammography in
      a health maintenance organization. Results of a randomized controlled trial.
AB  - BACKGROUND: Despite its demonstrated efficacy in reducing breast carcinoma
      mortality, screening mammography remains underutilized and its promotion in the
      primary care setting provides an important opportunity for intervention. METHODS:
      A randomized controlled trial was conducted in two sites of a health maintenance
      organization (HMO) serving an urban, minority population to evaluate the impact
      of patient and physician reminders on site visitation and mammography use.
      Eligible women (n = 2368) were randomly assigned to 1 of 4 intervention
      combinations (patient and physician reminders individually, together, or
      neither). The patient reminder letter invited mammography-due women to visit. The
      physician reminder was a notice placed in the medical record of mammography-due
      women. Logistic analysis and survival analysis were used to investigate the
      relationship of intervention status to visitation, time to a visit, and
      mammography use. RESULTS: The patient reminder intervention had no effect upon
      rates of study year visitation or mammography at either site. However, among HMO
      Site 2 enrollees with entitlement insurance, the median time to the next visit
      was reduced from 12 to 9 weeks in association with assignment to patient reminder
      intervention. The physician reminder intervention was also effective in
      increasing the rate of completed mammography at Site 2 among all assignees (36%
      vs. 22% for those with vs. those without physician reminders) and among assignees
      who visited (59% vs. 43%). CONCLUSIONS: Patient reminder letters had limited
      impact on visitation in this setting. Physician reminders are more effective but
      sites vary in their responsiveness. Further improvement in mammography
      utilization will require a better understanding of the determinants of patient
      and physician behavior.

PMID- 8859185
TI  - Breast preservation in stage I and II carcinoma of the breast. The University of
      Chicago experience.
AB  - BACKGROUND: Although breast conservation has received increased acceptance, there
      are still unresolved issues regarding local treatment techniques, such as the
      extent of surgery, in relation to the final margins of excision and the use of
      tumor bed boost radiation. The goal of this study was to determine the local
      control and breast preservation with particular emphasis on the importance of the
      final microscopic margins in patients receiving tumor bed boost therapy. METHODS:
      The authors analyzed 869 cases of Stage I and II breast carcinoma in 852 women
      who were treated with breast-conserving surgery and radiation therapy between
      1984 and 1994. The median follow-up was 43 months. Final microscopic margins were
      negative in 762 (88%), microscopically positive in 82 (9%), and unknown in 25
      (3%) of the patients. Negative margins were defined as no tumor cells at the
      surgical margin. The patients were treated with external beam radiation therapy
      to the entire breast to a median dose of 46 Gray (Gy). A boost to the tumor bed
      was delivered to 863 (99%) of the patients. The median tumor bed dose was 60 Gy.
      A multivariate analysis of factors impacting on the local control and overall
      survival was performed. Variables introduced into the model included size, age,
      lymph node status, microscopic margins, nuclear grade, histologic grade, and
      estrogen and progesterone receptor status. RESULTS: The actuarial 5-year local
      control rate was 97%. The median time to local failure was 32 months (range, 14
      69 months). In multivariate analysis, the only significant factor affecting local
      control was the status of margins. In patients receiving boost radiation to the
      excision site, the local control rate at 5 years was 98% and 89%, respectively,
      if the margins were negative or positive (P < 0.01). This resulted in 5-year
      actuarial breast preservation rates of 98% and 92% (P = 0.03). In the patients in
      whom the margins of excision were microscopically positive, the local control
      rate was 91% if the total dose to the tumor bed was > 60 Gy compared with 76% for
      a dose < or = 60 Gy (P = 0.05). The 5-year actuarial overall survival rate was
      89%. Approximately 94% of the women considered their cosmetic outcome good to
      excellent. CONCLUSIONS: By obtaining microscopically negative margins and using
      tumor bed boost therapy, excellent local control, breast preservation, and
      cosmesis can be achieved. In patients with microscopically positive margins, an
      acceptable local control rate can be achieved if a tumor bed boost is given.

PMID- 8859186
TI  - The New Mexico Mammography Project. Screening mammography performance in
      Albuquerque, New Mexico, 1991 to 1993.
AB  - BACKGROUND: This project was designed to collect and link population-based
      mammography and breast carcinoma data to assess the performance of community
      mammography screening. METHODS: Computerized data were collected from all
      radiology practices in Albuquerque, New Mexico. The data were linked by computer
      match to breast carcinomas in a statewide cancer registry. Analysis is based on
      126,466 screening mammogram studies performed on 87,443 female residents of New
      Mexico between the ages of 35 and 84 by 5 radiology groups. Sensitivity,
      specificity, positive predictive value, and call back rates were calculated as
      indicators of the discriminative performance of mammography. Carcinoma size and
      stage distribution were analyzed as outcome measurements. RESULTS: The computer
      match linked 634 breast carcinomas to the 126,466 screening mammogram series. The
      community-wide sensitivity was 79.9%, and specificity was 90.5%. The predictive
      value of an abnormal screen was 4.3%, and that of a biopsy recommendation result
      was 16.9%. The call back rate was 11.4%. The median invasive breast carcinoma
      size was 15 mm, 20.3% of carcinomas were in situ, 18.3% were lymph node positive,
      and 68.1% were Stage 0 or Stage 1. CONCLUSIONS: Mass screening mammography as
      practiced in Albuquerque, New Mexico, is able to detect breast carcinomas at
      early, treatable stages. The stage distribution of carcinomas is similar to that
      seen in successful clinical trials. However, measures of mammography performance
      show lower sensitivity, more additional studies, and more biopsy recommendations
      in this community setting than have been reported by expert mammographers.

PMID- 8859187
TI  - Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern.
AB  - BACKGROUND: To establish the prognosis, metastatic pattern, sites of treatment
      failure, and effect of various treatment modalities, a large series of patients
      with endometrial clear cell carcinomas (ECCC) was analyzed. METHODS: Between 1970
      and 1992, 181 patients with ECCC were treated. All pathologic slides and medical
      journals were reviewed. Clinical and histopathologic characteristics and type of
      treatment were analyzed with the univariate log rank test and multivariate Cox
      analysis. RESULTS: The 5- and 10-year actuarial disease free survival rates were
      43% and 39%, respectively. Pathologic stage, clinical stage, age, and myometrial
      invasion were the only significant prognostic variables in the univariate
      analysis. In the multivariate analysis, pathologic stage and age were the sole
      independent prognostic factors. Two-thirds of the patients with relapse relapsed
      outside the pelvis. The most frequent extrapelvic sites of relapse were the upper
      abdomen, lungs, and liver. Four of six patients treated with platinum-containing
      combination chemotherapy showed response, whereas none of the patients treated
      with single agent alkylating chemotherapy or progestagens responded. CONCLUSIONS:
      Pathologic stage and age were the two most important prognostic factors in clear
      cell carcinoma of the endometrium. In Stage I disease, depth of myometrial
      invasion, age, and subtype of clear cell carcinoma were the sole independent
      prognostic factors. Two-thirds of the patients relapsed outside the pelvis.

PMID- 8859188
TI  - Near tetraploid prostate carcinoma. Methodologic and prognostic aspects.
AB  - BACKGROUND: The clinical value of DNA ploidy analysis in prostate carcinoma has
      been an issue for investigation for more than 2 decades. In general, diploid or
      pseudodiploid tumors are associated with a favorable prognosis and aneuploid
      tumors with an unfavorable prognosis, irrespective of type of treatment. Tumors
      with DNA values in the tetraploid region (around 4c) present a diagnostic
      problem. Such DNA distributions may clearly represent aneuploid tumors with an
      unfavorable prognosis. However, a 4c distribution may conversely represent a
      tetraploid tumor (possibly a polyploid variant of the diploid tumor) with a
      favorable prognosis. Previous data from our laboratory indicate the existence of
      such a tetraploid subgroup. The goal of the current study was to investigate the
      diagnostic problem of 4c tumors in greater detail. METHODS: Ploidy classification
      of cytologic smears by image cytometry was performed in a retrospective study of
      334 patients with hormonally treated prostate carcinoma. Follow-up time was 30
      years or until death. RESULTS: Three ploidy types were defined: near-diploid (D
      type), near-tetraploid (T type), and highly aneuploid (A type). Tumors with a
      modal value within the tetraploid region were found in 27% (92 cases) of the
      total material. Of these, 9% were defined as T type and 18% as A type. Overall,
      37% of the tumors were classified as D type, 9% as T type, and 54% as A type. Of
      the A type tumors, one-third had modal DNA values in the tetraploid (4c) region.
      Multivariate analysis showed a statistically significant difference between A
      type tumors and D and T type, but not between D type and T type. Both D and T
      type tumors progressed slowly and killed the patients 5 to 30 years after
      diagnosis, whereas A type tumors progressed rapidly and killed the patients
      within 6 years of diagnosis. CONCLUSIONS: By image cytometry, prostate carcinoma
      can be divided into three ploidy types: D, T, and A type. Biologically, however,
      the tumors fall into only two groups: low grade malignant, pseudodiploid tumors
      of D or T type, and high grade malignant, highly aneuploid tumors of A type.

PMID- 8859189
TI  - Aggressive variants of chromophobe renal cell carcinoma.
AB  - BACKGROUND: Chromophobe renal cell carcinoma (RCC) is a distinctive subtype of
      RCC with a more favorable prognosis than clear cell RCC. We describe the
      pathologic features of 23 solitary cases and 2 cases with coexistent papillary
      RCCs, 7 of which developed metastases. METHODS: Cases were retrieved from the
      pathology files of our institutions. Clinical follow-up was obtained from the
      medical records. DNA analysis was performed on Feulgen-stained slides using image
      analysis. RESULTS: Twenty-five cases were identified. All cases had
      characteristic pathologic features, including diffuse cytoplasmic reactivity for
      Hale's colloidal iron. DNA ploidy analysis of ten cases revealed a diploid
      pattern in five, a hyperdiploid pattern in four, and a hypodiploid pattern in
      one. Follow-up was available for 20 cases, and metastases developed in 7 (from 4
      to 120 months after surgery). In 5 of these cases, the tumors were solitary and
      more than 8 cm in greatest dimension and metastases developed in the liver. In
      both cases with papillary RCCs in the same kidney, metastases developed in the
      lung, although which tumor metastasized is unknown. CONCLUSIONS: Despite the
      overall favorable prognosis for chromophobe RCC, large tumors and those with
      coexistent papillary RCCs may produce in metastases.

PMID- 8859190
TI  - Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein
      and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the
      bladder.
AB  - BACKGROUND: Transitional cell carcinoma (TCC) of the bladder displays an
      unpredictable biologic behavior and the morphologic methods of grading tumor
      malignancy are often insufficient to predict the clinical outcome of patients
      with TCC of the bladder. Thus, the new indicator should reliably reflect
      prognosis. In this study, the authors determined the prognostic significance of
      proliferating cell nuclear antigen (PCNA), p53 protein, and nm23 protein, as well
      as nuclear DNA content in specimens with TCC of the bladder. METHODS: Paraffin
      embedded materials taken from 77 patients with nonmetastatic untreated TCC of the
      bladder (classified as pTa-3b, NO, MO) treated with total cystectomy were
      employed in this study. PCNA expression, p53 protein and nm23 protein
      immunoreactivities, and the parameters for nuclear DNA content such as 2c
      deviation index (2cDI) and 5c exceeding rate (5cER) were evaluated using a
      computer-assisted image analyzer, and the results were compared with histologic
      findings and clinical outcome. RESULTS: PCNA expression positively correlated
      with p53 protein and nm23 protein immunoreactivities, 2cDI value, and 5cER. In
      addition, histologic grade positively correlated with all of these five
      parameters. Similarly, pT category and disease progression positively correlated
      with all of the five parameters, except for nm23 protein immunoreactivity. In
      tumors with high genetic instability as judged by 2cDI and 5cER, both PCNA
      expression and p53 protein immunoreactivity were elevated, whereas nm23 protein
      immunoreactivity was not. However, the percent coefficient of variation in PCNA
      expression was smaller than that observed in p53 protein immunoreactivity in each
      group of genetic instabilities. In univariate analysis, prognostic potential was
      found with histologic grade, pT category, PCNA expression, p53 protein
      immunoreactivity, 2cDI value, and 5cER, but was not noted in nm23 protein
      immunoreactivity. Multivariate analysis indicated that quantity and intensity of
      PCNA expression (chi 2 = 8; P = 0.0047 for quantity and chi 2 = 8.71; P = 0.0032
      for intensity) and 2cDI value (chi 2 = 5.52; P = 0.0019) were independent
      variables of histologic grade and pT category when predicting survival. However,
      p53 protein and nm23 protein immunoreactivities and 5cER were not of independent
      significance. CONCLUSIONS: The tumor growth fraction as assessed by PCNA
      immunostaining is an independently significant predictor for survival of patients
      with TCC of the bladder.

PMID- 8859191
TI  - A carboplatin-based regimen for the treatment of patients with advanced
      transitional cell carcinoma of the urothelium.
AB  - BACKGROUND: Many patients with advanced transitional cell carcinoma are unable to
      receive cisplatin-based therapy. The efficacy and toxicity of a carboplatin-based
      regimen in the treatment of patients with advanced transitional cell carcinoma
      was therefore evaluated. METHODS: Twenty-three patients with advanced
      transitional cell carcinoma were treated. Metastatic disease was present in 19 of
      23 patients (83%) whereas 4 patients with T4, and/or N1, disease were treated.
      Patients were treated every 28 days with methotrexate, 30 mg/m2 intravenously
      (i.v.) on Days 1 and 15, along with leucovorin, 15 mg/m2 orally every 6 hours, 3
      times daily beginning 24 hours after each methotrexate dose; vinblastine, 3 mg/m2
      i.v. on Days 1 and 15; mitoxantrone, 15 mg/m2 i.v. on Day 1; and carboplatin, 300
      mg/m2 i.v. on Day 1, adjusted for creatinine clearance (MVNCa). Dosage in
      subsequent cycles was adjusted according to hematologic toxicity. RESULTS: Median
      age was 70 years (range, 52-83 years) and median pretreatment creatinine
      clearance was 50 mL/min (range, 30-106 mL/min). Of 23 patients, 8 (34.8%)
      obtained a complete response, and 5 (21.7%) obtained a partial response. The
      overall response proportion was 56.5% (95% confidence interval, 34.5-76.8%).
      Median survival was 10 months (range, 1-44+ months). Toxicity was moderate. Grade
      4 neutropenia occurred in 10 of 107 (9.3%) administered treatment cycles; Grade 4
      thrombocytopenia occurred in 11 of 107, (10.3%). There were 4 episodes of febrile
      neutropenia (3.7% of cycles). Renal, neurologic, or otic toxicity were not
      observed. Age older than 70 did not appear to impact on response proportion,
      survival, and toxicity. CONCLUSIONS: The carboplatin-based MVNCa regimen is
      active in the treatment of patients with advanced transitional cell carcinoma and
      is well tolerated. Therapy with this regimen may be a less toxic alternative for
      patients for whom treatment with cisplatin is not an option.

PMID- 8859192
TI  - Brain metastases. Histology, multiplicity, surgery, and survival.
AB  - BACKGROUND: With the advent of new therapies for metastatic carcinoma to the
      brain, patterns of intracranial disease and factors influencing survival become
      important considerations when examining potential treatment options. METHODS: The
      records of 729 patients with metastases to the brain treated during the period
      between 1973 to 1993 were reviewed. RESULTS: Primary tumor histologic type in
      order of descending frequency included nonsmall cell lung carcinoma (NSCLC),
      breast carcinoma, small cell lung carcinoma (SCLC), malignant melanoma, renal
      cell carcinoma, gastrointestinal carcinoma, uterine/vulvar carcinoma, and unknown
      primary carcinoma. There were 384 patients (53%) with a single brain metastasis,
      which was encountered most commonly in patients with prostate carcinoma and least
      often in patients with SCLC. Multiple metastases were present in 345 patients
      (47%). The median duration from diagnosis to presentation with a brain metastasis
      was 12 months, ranging from 3 months for patients with NSCLC to 53 months for
      patients with breast carcinoma. The median duration from presentation with brain
      metastases to death was 4 months, ranging from 3 months for patients with SCLC to
      13 months for patients with prostate carcinoma. Median survival from presentation
      with brain metastases to death was 5 months for patients with single lesions and
      3 months for patients with multifocal disease (P = 0.0001). Median survival for
      patients with a single lesion was 11 months with surgery and 3 months without
      surgery (P = 0.0001). Surgery did not significantly influence survival in
      patients with multiple metastases. CONCLUSIONS: Dissemination of systemic
      carcinoma to the brain continues to carry a poor prognosis. Knowledge of the
      metastatic patterns and limited survival associated with specific tumor types may
      be useful for guiding future therapeutic intervention.

PMID- 8859193
TI  - Gliomatosis cerebri. Results with radiation therapy.
AB  - BACKGROUND: This review was undertaken to determine the outcome for patients
      diagnosed in the modern era and treated with radiation therapy. METHODS: Using
      the tumor registries of six institutions in a large metropolitan area, cases of
      gliomatosis were identified and retrospectively reviewed. RESULTS: The clinical
      course for each patient was unique. Deterioration during treatment, brief
      stabilization, and reversal of the clinical signs and symptoms with stability and
      high quality of life at 16 months from diagnosis characterized Patients 1, 2, and
      3, respectively. CONCLUSIONS: Radiotherapy for gliomatosis appears to stabilize
      or improve neurologic function in some patients. Its impact on survival will
      await additional reports and longer follow-up.

PMID- 8859194
TI  - Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients
      with advanced colorectal or gastric carcinomas.
AB  - BACKGROUND: The biochemical modulation of 5-fluorouracil (5-FU) by leucovorin
      (LV) has demonstrated significantly increased response rates in comparison with
      the use of 5-FU alone in patients with advanced colorectal carcinoma. However,
      the higher response rate of LV/5-FU may occur at the expense of increased
      toxicity and side effects such as diarrhea, myelosuppression, and mucositis.
      During chemotherapy, a high incidence of hypocalcemia associated with this
      chemotherapy regimen was noted. This study was therefore aimed at assessing the
      side effects of chemotherapy using low dose LV/5-FU on calcium metabolism.
      METHODS: Twenty-five patients with advanced gastric or colorectal carcinoma were
      treated with chemotherapy comprised of low dose LV administered at 20 mg/m2/ day
      by intravenous bolus, followed by 1-hour intravenous infusion of 5-FU at 425-600
      mg/m2/day for 5 consecutive days every 28 days. RESULTS: The toxic effects were
      generally mild, and included diarrhea, mucositis, leukopenia, and
      nausea/vomiting. Fifteen patients (65%) experienced hypocalcemia. The plasma 1,25
      (OH)2D3 levels were significantly reduced on Day 5 due to the chemotherapy.
      CONCLUSIONS: The toxic effects of the regimen were generally mild. However, a
      high percentage of hypocalcemia occurred with the combination of LV/5-FU. It is
      therefore necessary to examine carefully the serum calcium levels of patients
      when using this chemotherapeutic modality.

PMID- 8859195
TI  - Cisplatin administration to gynecologic cancer patients. Long-term effects on
      hearing.
AB  - BACKGROUND: Cisplatin is known to create an acute dose-related ototoxic effect.
      There are unanswered questions regarding the long term effect of cisplatin on
      hearing in gynecologic cancer patients. METHODS: A retrospective review of 59 to
      115 months' duration was performed on 184 women with gynecologic cancer who were
      treated with cisplatin-based chemotherapy between 1982 and 1986. Twenty-six of 40
      survivors were again tested audiometrically with the same audiologic equipment.
      RESULTS: Fourteen patients (54%) had significantly progressive hearing loss (> or
      = 15 decibels) at long term follow-up compared with the posttreatment control.
      These changes were generally small and restricted to three frequencies or fewer
      in one of the patient's ears. The changes corresponded to the expected age effect
      upon hearing. Only 2 patients (8%) showed more severe hearing threshold changes.
      The hearing loss in one of the two patients might represent degenerative changes
      induced by cisplatin treatment, whereas in the other patient the etiologic
      background to the hearing loss remains unknown. CONCLUSIONS: This study does not
      provide any strong evidence for a delayed ototoxic effect of cisplatin that
      should influence therapeutic strategy. Patients who receive moderate dose
      cisplatin therapy, 50 mg/m2 per body surface area every 4 weeks, have a
      negligible long term risk of a drug-induced social hearing handicap.

PMID- 8859196
TI  - Clinicopathologic, cytogenetic, and molecular studies of 13 Chinese Patients with
      Ki-1 anaplastic large cell lymphoma. Special emphasis on the tumor response to 13
      cis retinoic acid.
AB  - BACKGROUND: The clinicopathologic and molecular features of the newly
      characterized Ki-1 lymphoma, although well studied in Western countries, are less
      well described in Asia. METHODS: Pathology material of lymphoma cases,
      consecutively diagnosed at our institution between 1986 and 1994, was reviewed.
      The cases fulfilling the diagnostic criteria of Ki-1 lymphoma were selected, and
      their clinicopathologic features were studied. Immunohistochemistry and
      cytogenetic studies of the lymphoma tissues, and molecular analysis for
      nucleophosmin (NPM) gene translocation were performed. RESULTS: A total of 13
      cases (2.3%) of Ki-1 large cell lymphoma were identified from a total of 572
      cases of non-Hodgkin's lymphoma diagnosed during this period of time. There were
      10 men and 3 women with a median age of 43 years (range, 18 to 61 years). The
      initial presenting sites included the skin alone in five cases, lymph node alone
      in one case, both skin and lymph node in five cases, and the stomach in one case.
      All cases had large cell morphology, with the majority of the neoplastic cells
      expressing Ki-1 antigen (CD30). Except for the case with gastric involvement, all
      other cases were T-cell lymphomas. One of seven cases examined had chromosomal
      abnormality of t (2;5). Rearrangement of the NPM gene at chromosome 5 was
      detected by Southern blot analysis in three of nine cases. Two of seven cases
      tested by reverse-transcriptase polymerase chain reaction showed fusion of the
      NPM gene and anaplastic lymphoma kinase gene. Seven (78%) of 9 patients who had
      received systemic chemotherapy with a standard cyclophosphamide, doxorubicin,
      vincristine, and prednisolone regimen obtained a complete remission (CR). The
      median duration of remission was 33 months. Three (60%) of 5 patients, of whom 4
      recurred from previous intensive chemotherapy, achieved a prolonged CR with
      treatment with 13-cis retinoic acid (RA). The median survival of the whole group
      has not yet been reached at a median follow-up of 40 months. CONCLUSIONS: The
      clinicopathologic and molecular features of Ki-1 lymphoma of Chinese patients are
      comparable to those reported from Western countries. 13-cis RA appears to be an
      effective treatment of Ki-1 lymphoma.

PMID- 8859197
TI  - Non-Hodgkin's lymphomas in Thailand. A retrospective pathologic and clinical
      analysis of 1391 cases.
AB  - BACKGROUND: Geographic variations in the histopathologic pattern of non-Hodgkin's
      lymphoma (NHL) are well documented. Insight into this epidemiologic data might
      shed light on the underlying etiology. Currently, there is a paucity of
      information regarding the pattern of NHL occurring in Thailand and Southeast
      Asia. The current nationwide study was undertaken to obtain a clearer definition
      of the disease among Thais and to compare this information with data from other
      Asian and Western countries. METHODS: A retrospective analysis of histopathologic
      subtypes and clinical features was conducted in 1391 patients (age > or = 15
      years) with NHL, who were treated at 6 major medical centers in 4 representative
      areas of Thailand. One hundred and thirty unselected cases were
      immunohistochemically studied. The reports from other countries used for
      comparison were identified through a computerized search on MEDLINE. RESULTS: Of
      the total cases studied, follicular lymphomas constituted 3.8% and diffuse
      lymphomas 91.4%. The frequency of low and intermediate grade (including large
      cell immunoblastic, using the Working Formulation) were 12.8% and 72.9%,
      respectively. The most common histologic subtype was the diffuse large cell and
      large cell immunoblastic entity, which constituted 39.9% of the cases studied.
      The rate of small lymphocytic and diffuse small cleaved subtypes were higher than
      in the United States. Of the 130 cases studied, T-cell lymphoma comprised 16.1%,
      which was much less than in Japan, China, or Taiwan. CONCLUSIONS: The
      histopathologic pattern of NHL in Thailand was characterized by the features
      noted for Asia, i.e., a low rate of the follicular entity and a preponderance of
      the diffuse aggressive subtypes. In addition, the frequency of the small
      lymphocytic and diffuse small cleaved subtypes were increased compared with the
      Western population and the rate of T-cell lymphoma appeared to be less than in
      Far East Asia.

PMID- 8859198
TI  - National Cancer Data Base report on esophageal carcinoma.
AB  - BACKGROUND: The prognosis for patients with esophageal carcinoma is poor, with
      less than fifty percent surviving 1 year after diagnosis. Although diagnostic and
      staging methods have improved, a large proportion of patients present with
      advanced disease. Research is being conducted to determine what multimodality
      treatment regimens provide the best local control and survival. METHODS: Using
      the National Cancer Data Base's most current accrual of oncologic data for cases
      diagnosed in 1988 and 1993, patterns of care and outcome were analyzed for
      esophageal carcinoma. RESULTS: A substantial increase was demonstrated between
      1988 and 1993 in the proportion of esophageal adenocarcinomas and patients
      presenting with Stage IV disease. The therapeutic regimen most frequently
      employed in 1993 was combined radiation therapy and chemotherapy, which rose 8.2%
      from 2.2% in 1988. CONCLUSIONS: The dramatic rise across the years of this study
      in the occurrence of esophageal adenocarcinomas indicates a need for developing
      strategies to evaluate Barrett's preneoplastic mucosal changes more precisely.
      The increasing use of combined chemotherapy and radiation therapy reflects the
      results of randomized trials that have demonstrated improved response and outcome
      for this combined regimen compared with radiation therapy alone. There was no
      substantial increase in the use of surgical resection with chemotherapy and
      radiation therapy throughout these years.

PMID- 8859199
TI  - The National Cancer Data Base report on patterns of hospital reporting.
AB  - BACKGROUND: Previous Commission on Cancer data from the National Cancer Data Base
      (NCDB) have examined time trends in stage of disease, treatment patterns, and
      survival for selected cancers. The most current (1993) data are described here.
      METHODS: Five calls for data have yielded a total of 3,700,000 cases for the
      years 1985 through 1993, including 477,679 cases for 1988, and 608,593 cases for
      1993, from hospital cancer registries across the U.S. RESULTS: The most recent
      call for data for 1993 comprised 52% of the estimated new cases of cancer in the
      U.S. The country was comprised of 6 regions, with the Mountain and Southeast
      regions having the highest regional reporting of new cases of cancer (69% and
      55%, respectively) and the Northeast and Pacific regions having the lowest (47%
      each). Approximately 96% of patients received their treatment at the reporting
      hospital. The 4 most common carcinomas were breast (15.7%), lung (14.6%),
      prostate (14.2%), and colon (7.5%) and comprised the majority of new cases.
      Trends in patterns of care for breast carcinoma were analyzed for possible bias
      in the 1988 and 1993 periods. When hospitals reporting only in 1988 or in 1993
      were compared with hospitals reporting at both time points, the only differences
      were small differences in ethnic participation. These differences were less than
      1.5% in the proportion of African Americans reported in the different time
      periods. There were no significant differences in the downstaging of breast
      carcinoma, or the role of conservative surgery or adjuvant radiation therapy.
      CONCLUSIONS: The NCDB is a cancer management and outcomes data base for health
      care organizations that presently comprises 52% of the estimated new cases in the
      U.S. This will increase to 80% as the approved hospitals of the Commission on
      Cancer are required to report to the NCDB. Comparison of breast carcinoma
      findings at two time periods appeared similar regardless of hospital reporting
      set (i.e., set of hospitals reporting for one period versus both periods).

PMID- 8859200
TI  - The National Cancer Data Base report on breast carcinoma characteristics and
      outcome in relation to age.
AB  - BACKGROUND: Previous data from the National Cancer Data Base have examined time
      trends in stage of disease, treatment patterns, and survival for selected
      cancers. The most current (1993) data for breast carcinoma are described here.
      METHODS: Five Calls for Data have yielded a total of 508,724 breast cancer cases
      diagnosed from 1985 to 1993, from hospital cancer registries throughout the U.S.
      RESULTS: Women younger than age 35 had a lower rate of ductal carcinoma in situ,
      higher grade primary tumors, more advanced American Joint Committee on Cancer
      stage disease, and poorer 5-year relative survival than older premenopausal
      women. African American women were more likely to have advanced disease than non
      Hispanic whites in all three age groups analyzed. Improved time trends of early
      detection of breast carcinoma and use of breast conservation treatment are
      reported. The overall prognosis for breast carcinoma remains relatively good for
      all age groups when compared with other cancers. CONCLUSIONS: These data are
      consistent with the hypothesis that younger women are at increased risk for
      biologically more aggressive breast carcinoma.

PMID- 8859201
TI  - Tachycardia in a 60-year-old man.

PMID- 8859202
TI  - Respiratory distress in a patient with skin lesions.

PMID- 8859203
TI  - The case for allergy immunotherapy.

PMID- 8859204
TI  - Helping Alzheimer's research.

PMID- 8859205
TI  - Expanding zoster's differential diagnosis.

PMID- 8859206
TI  - Retrieving medical information.

PMID- 8859207
TI  - Understanding drug addiction: implications for treatment.
AB  - The addicted brain is qualitatively different from the nonaddicted brain, in ways
      that include glucose use, gene expression, and responsiveness to environmental
      cues. Such discoveries place researchers in the early but hopeful stages of
      translating fundamental findings into new treatments that address the
      neurobiologic basis of drug craving--even for cocaine, against which there are
      currently no pharmacologic interventions.

PMID- 8859208
TI  - Global expansion of HIV infection and AIDS.
AB  - The decline of new HIV infections among subgroups in industrialized countries has
      created a false sense of security; globally, about 13,000 new infections occur
      each day. In developing countries, limited health care spending bars all but a
      privileged few from access to new treatment. In the absence of an effective
      vaccine and intensified prevention, spread of the virus will continue unabated.

PMID- 8859209
TI  - Salty language is confusing.

PMID- 8859210
TI  - Management issues in asymptomatic carotid stenosis.
AB  - In the absence of symptoms, management is not clear-cut; indeed, are symptoms
      truly absent or merely unacknowledged? The workup must carefully balance risks
      associated with carotid endarterectomy against risks of nonsurgical treatment.
      Psychosocial factors are an important part of the balance; some patients prefer
      to live with the risk of stroke from essentially untreated disease.

PMID- 8859211
TI  - Molecular mediators of asthma: current insights.
AB  - With advances in molecular biology, the complex inflammatory events that underlie
      asthma are being unraveled. The players are diverse, involving two populations
      each of mast cells and helper T cells, eosinophils, bronchial endothelial and
      epithelial cells, and an array of vasoactive and bronchoactive mediators. The
      clinical message is already clear: Treat the inflammation early.

PMID- 8859212
TI  - Medical Therapy of GERD: current state of the art.
AB  - A proton pump inhibitor is the most cost-effective choice for severe disease and,
      in low doses, for moderate disease. Patients with mild disease and infrequent
      relapses can be managed with a H2-receptor antagonist, an antacid, or cisapride.

PMID- 8859213
TI  - Paying attention to gender in the medical interview.

PMID- 8859214
TI  - The role of history taking in the diagnosis of asthma.

PMID- 8859215
TI  - Rapidly progressive deafness in a young woman.

PMID- 8859216
TI  - Chest pain in a woman who bruised easily.

PMID- 8859217
TI  - Soluble receptors for cytokines and growth factors.
AB  - Soluble cytokine and growth factor receptors are currently believed to play an
      important role in the regulation of biological activities of their ligands. In
      this review, the current ideas on the mechanisms and regulation of generation of
      soluble receptors and their possible physiological functions are presented.
      Furthermore, implications of soluble cytokine and growth factor receptors as
      disease markers and therapeutical agents are summarized and discussed.

PMID- 8859218
TI  - Complement activation by C-reactive protein on the HEp-2 cell substrate.
AB  - The complement (C) activation by C-reactive protein (CRP) in acute-phase sera is
      routinely tested in our laboratory by means of an indirect immunofluorescence
      method (C3-IFT) on rat kidney sections. This C3-IFT assay is based on the binding
      of CRP to the renal tissue followed by the fixation of C4 and C3 components to
      distinct vessel-associated medullary structures as a result of CRP-mediated C
      activation in vitro. While the activation cascade leading to the deposition of C4
      and C3 could previously be deduced experimentally, we were unable as yet to
      visualize CRP and the components of the C1 complex on kidney sections when
      testing patients' sera by indirect immunofluorescence. In an attempt to analyze
      the mechanisms of unexpectedly negative C3-IFT results (e.g. bacterial
      endocarditis) we employed monolayers of fixed HEp-2 cells which have previously
      been shown to be a suitable substrate for CRP binding. By incubating purified
      native CRP supplemented with normal human serum as a source of C we detected the
      C components Clq, Clr, Cls, C4 and C3 in the same speckled immunofluorescent
      pattern on HEp-2 cell nuclei as described characteristically for CRP binding. The
      serial activation steps from CRP up to C3 could also be followed on HEp-2 cells
      using C3-IFT-positive acute-phase sera. However, certain C3-IFT-negative acute
      phase sera showed an arrest between Cls and C4 of the CRP-mediated C activation
      cascade. HEp-2 cells can thus be used to monitor the process of autologous C
      activation initiated by endogeneous CRP in patients' sera. In contrast to native
      CRP, urea-modified CRP (mCRP) did not bind to HEp-2 cell nuclei, but was detected
      in association with distinct filamentous cytoplasmic structures. Unlike its
      native counterpart, binding of mCRP was not followed by a deposition of C
      components.

PMID- 8859219
TI  - Spontaneous degranulation of cultured bone-marrow-derived immature mast cells
      from X-linked immunodeficient (Xid) mice.
AB  - IgE-mediated, antigen-dependent stimulation of immature mouse mast cells cultured
      in IL-3-containing media produces secretion by granule exocytosis. Similar
      cultured mast cells were derived from X-linked immunodeficient (Xid) mice and
      examined by electron microscopy. In these cultures, Xid mast cells were also
      immature. In contrast to cultures obtained from control mice, 10-20% of the
      immature mast cells of Xid origin were undergoing secretion by granule extrusion
      in the absence of any secretogogue. Spontaneous secretion may be related to
      discordered tyrosine kinase function and/or signal transduction pathways in the
      Xid mouse.

PMID- 8859220
TI  - Histamine augments VCAM-1 expression on IL-4- and TNF-alpha-stimulated human
      umbilical vein endothelial cells.
AB  - Interaction between vascular cell adhesion molecule-1 (VCAM-1) on endothelial
      cells and CD49d molecules on eosinophils is thought to mediate the selective
      infiltration of eosinophils into inflamed tissues in allergic disease. IL-4 and
      TNF-alpha are associated with allergic conditions, and they have been shown to
      selectively augment VCAM-1 expression on endothelial cells, suggesting that they
      may be responsible for VCAM-1 expression in allergic disease. We used
      immunocytochemical staining analysis to examine the effect of chemical mediators,
      including histamine, leukotrienes and platelet-activating factor (PAF), on VCAM-1
      expression in IL-4- and TNF-alpha-stimulated endothelial cells. Histamine,
      significantly augmented (p < 0.05 to p < 0.01) VCAM-1 expression in both IL-4-
      and TNF-alpha-stimulated endothelial cells. IL-4 and TNF-alpha were found to have
      a synergistic effect on endothelial cell VCAM-1 expression, when compared with
      the effect of stimulation with each of these cytokines separately, and the
      addition of histamine further increased VCAM-1 expression. This enhancing effect
      of histamine was inhibited by the presence of mepyramine and thioperamide but not
      by cimetidine. Another chemical mediator, PAF, failed to induce any increase in
      VCAM-1 expression, however, leukotrienes augmented it slightly in a narrow range
      of concentrations. The histamine-induced augmentation of VCAM-1 expression was
      reflected functionally by many more eosinophils attaching to endothelial cells
      than to cells stimulated with both cytokines. This attachment of eosinophils was
      inhibited by the presence of antibody to VCAM-1 and CD49d. Addition of histamine
      10 h after stimulation with both cytokines still induced an increase in VCAM-1
      expression. In addition, an inhibitor of RNA polymerase, alpha-amanitin, dose
      dependently decreased this histamine-induced augmentation of VCAM-1 expression.
      These findings strongly suggest that histamine upregulates VCAM-1 expression at
      the transcriptional level through newly generated of mRNA in endothelial cells
      stimulated with IL-4 and TNF-alpha.

PMID- 8859221
TI  - Local production of interleukin-5 by T lymphocytes is associated with recruitment
      of eosinophils in patients with eosinophilic granuloma of the soft tissue.
AB  - Eosinophilic granuloma of the soft tissue (EOSG) is a rare disease of unknown
      cause. Since the in vivo mechanism of eosinophilia remains unclear, the present
      study was performed to investigate the mechanism of the infiltration of
      eosinophils into the granuloma tissue. Immunohistochemical techniques and an
      eosinophil chemotactic assay were used in analysis. Peripheral blood eosinophils
      obtained from one patient showed an increased chemotactic response against tissue
      extract that was inhibited by pretreatment with anti-IL-5 antibodies. Eosinophils
      obtained from the peripheral blood of patients with EOSG showed a significant
      increase in chemotactic activity toward 10(-9) M recombinant human (rh) IL-5
      versus that of healthy individuals, whereas eosinophils from granuloma tissue
      showed no chemotactic response toward rhIL-5, indicating that IL-5 may deactivate
      the eosinophils. Immunohistochemical studies showed that CD4+ cells were
      predominantly found in the extrafollicular region, along with interleukin-5+ (IL
      5) cells. Staining of the adjacent 3-micrometers sections for CD3, eosinophils,
      and IL-5 revealed that most of the IL-5 immunoreactive CD3+ cells exhibited
      cytoplasmic staining. Conversely, 97% of IL-5+ eosinophils were stained
      peripherally in a ring-like manner, suggesting that IL-5 was bound to its cell
      surface receptor on the eosinophil. IL-5 mRNA expression was detectable in the
      CD3+T lymphocytes but not in eosinophils from granuloma tissue. These findings
      suggest that locally produced IL-5 from T lymphocytes may enhance the
      infiltration of eosinophils into the eosinophilic granuloma.

PMID- 8859222
TI  - Cytokine priming of human basophils: description of allergen 'nonreleasers'.
AB  - Interleukins 3 and 5 and GM-CSF enhance histamine release from basophils
      triggered by various stimuli. In this report, we describe a subset of allergic
      patients whose basophils release histamine in response to allergen only when
      primed with cytokine. In the absence of cytokine, there is no detectable response
      to allergen. These patients, who represent 4-13% of the allergic population,
      cannot be distinguished by skin test reactivity or severity of allergic symptoms.
      Allergen nonreleasers tend to have lower titers of allergen-specific IgE than the
      majority of atopic subjects, but this difference is not significant (average
      titer of 29.8 for nonreleasers vs. 188 for typical allergies; p = 0.15). They
      release histamine normally with anti-IgE and with fMLP, indicating that basophils
      are responsive to signalling through the IgE receptor, and there is no intrinsic
      defect in degranulation. Thus, in these patients, the IgE-mediated release of
      inflammatory mediators from basophils is dependent on, rather than merely
      enhanced by, T cell cytokines. The relationship between these patients and the
      previously described anti-IgE 'nonreleasers' is discussed.

PMID- 8859223
TI  - IgE allotypes in sera of mice with autoimmune diseases and in mice with graft
      versus-host disease after transfusion or bone marrow transplantation.
AB  - Isotype- and allotype-specific IgE determinations by sandwich ELISA with
      monoclonal antibodies to Igh-7 (6HD5, HMK-12), Igh-7a (No. 297) and Igh-7b /JKS
      6) were used to qualitate antibodies of the IgE class. The sensitivity of the
      method is 0.1 ng/ml. Serum IgE levels were much higher in mice infected with
      Nippostrongylus brasiliensis. In sera of BALB/c, AKR and C3H/JCL mice only IgEa,
      in sera of C57BL/6 and CB-20 only IgEb, in sera of (BALB/c x C57BL/6) F1 mice,
      both allotypes were detected, as expected. In mice with autoimmune diseases, such
      as NZB, NZW, (NZB x NZW) F1, MRL/Ipr and MRL/n strains which all belong to the
      IgEa allotype group, IgE and IgEa were very high. In the sera of BXSB mice, both
      IgEa and IgEb were detected. Both IgEa and IgEb from donor and host were
      increased in the sera of mice with graft-versus-host disease after
      transplantation but only the IgEa (from the donor) was increased in mice with
      graft-versus-host disease after bone marrow transplantation. In the former, both
      B cells (from donor and host) secreted IgE, whereas in the latter only the donor
      cells did. These are the first observations showing the importance of IgE
      allotype secretion as an indication of graf-versus-host disease.

PMID- 8859224
TI  - In vivo effects of monoclonal antibody against ICAM-1 and LFA-1 on antigen
      induced nasal symptoms and eosinophilia in sensitized rats.
AB  - We applied anti-ICAM-1 and anti-LFA-1 monoclonal antibody (mAb) to ovalbumin
      sensitized rats and examined the effects on nasal eosinophilia and nasal symptoms
      following topical antigen challenge. In a general and local immunization (GLI)
      group of rats, the mAbs were applied during the booster topical immunization
      period. In a general immunization group and a local immunization (LI) group of
      rats, the mAbs were applied during the immunization period. The number of sneezes
      and nasal scratching movements occurring soon after topical antigen (Ag)
      challenge was significantly suppressed in the GLI and LI group rats. Eosinophil
      infiltration into nasal mucosa 24 h after Ag challenge was also significantly
      suppressed in GLI and LI group rats. These findings suggest that the ICAM-1/LFA-1
      system is important in topical allergic inflammation in rats.

PMID- 8859225
TI  - Induction of histamine release from non-immunized guinea pigs: a possible
      involvement of lectin-like factor(s) in pollinosis.
AB  - To investigate nonimmune pathogenic functions of pollens, vascular permeability
      enhancement (VPE) activity of pollen extracts was examined using guinea pigs
      nonimmunized against pollens. Ryegrass, ragweed, mesquite and almond, but not
      common cattail and sumac, induced VPE which was inhibited primarily by an anti
      histamine drug. Ryegrass pollen VPE activity was extracted more at pH 7.3 than at
      pH 6.5 or 8.0 and the maximal activity was extracted in 30 min. Interestingly,
      more than 60% of the maximal activity was extracted in 5 min. The maximal VPE
      activity had a dose-dependency similar to histamine (3 x 10(-5) M) but lasted
      longer than the histamine activity. The VPE activity was inhibited by
      oligomannose-glycosylated ovalbumin or avidin, as well as the oligosaccharides
      but not by the deglycosylated proteins. These results indicate that some pollens
      contain lectin-like, histamine-releasing factor(s), which may be involved in part
      in pollinosis, by inducing mast cell degranulation through a nonimmune mechanism
      and resulting in allergy-like symptoms.

PMID- 8859226
TI  - Recurrent hearing impairment and nystagmus induced by repeated antigen exposure
      in actively sensitized guinea pigs.
AB  - Although many studies have suggested a relation between allergy and Meniere's
      disease, the pathophysiology of this condition remains controversial. The aim of
      this study was to clarify whether an anaphylactic reaction in the inner ear can
      disturb hearing and equilibrium, and whether such disturbances recur in response
      to repeated anaphylactic reactions. Increases in audiological threshold,
      nystagmus, and endolymphatic hydrops were observed in response to a single
      exposure to antigen administered to actively sensitized guinea pigs. The increase
      in audiological threshold was maximal 10 h after antigen challenge (p < 0.005)
      and returned to the baseline level after 7 days. Nystagmus and the increase in
      audiological threshold induced by antigen exposure were inhibited by prior
      administration of pemirolast potassium (p < 0.05), an inhibitor of chemical
      mediator release from mast cells. A second challenge with antigen 7 days after
      the first also induced an increase in audiological threshold (p < 0.05) and
      nystagmus. These results suggest that studies of repeated antigen challenge in
      actively sensitized animal models may increase our understanding of the
      pathophysiology of Meniere's disease.

PMID- 8859227
TI  - Host genetic and adjuvant factors influence epitope specificity to a major
      recombinant grass allergen.
AB  - The role of host genetic and adjuvant factors in the induction of immune
      responses to a major recombinant Kentucky bluegrass allergen was examined
      utilizing five strains of mice and two different adjuvants. Analysis of the
      recombinant allergen-specific antibodies induced in these strains indicated that
      the antibodies of various isotypes were differentially regulated. In terms of IgE
      antibody response, BDF1 and DBA/2 were characterized as high responder, whereas
      BALB/C, CBA/J and C57BL/6 were intermediate and SJL was a low responder. In
      different strains, both dextran sulfate (DS) and complete Freund's adjuvant
      (CFA), as adjuvants, induced recombinant allergen-specific IgE antibodies of
      similar titer, however, CFA induced higher IgG2a and lower IgM antibodies
      compared to DS. Further, analysis of T cell proliferative responses of the
      splenocytes of different strains demonstrated that these strains varied also in
      their capacity to respond to synthetic peptides. Furthermore, utilizing a panel
      of synthetic peptides corresponding to the recombinant allergen, we demonstrated
      that the antibodies induced by the recombinant allergen with CFA in different
      strains vary with respect to their epitope specificity. In the BDF1 strain,
      compared to DS, CFA as adjuvant induced recombinant allergen-specific antibodies
      of additional peptide specificity. Taken together, these results suggest that
      both host genetic background and adjuvants govern the fine specificity of
      antibodies produced against this recombinant Kentucky bluegrass allergen.

PMID- 8859228
TI  - Early sensitization to farming-related antigens among young farmers: analysis of
      risk factors.
AB  - It was the aim of this study to investigate the prevalence of and risk factors
      for IgE- and IgG-mediated allergy in young farmers. We investigated 147 young men
      attending a farming college in the Austrian Tyrol and 57 age-matched pupils at a
      grammar school. All individuals completed a questionnaire and had spirometry,
      skin prick tests, total and specific IgE analysis, and testing for precipitins
      against thermophilic actinomycetes and true fungi. In the farming group, a family
      history of atopy or asthma was reported less frequently than in the control group
      (p < 0.001) but there were no differences in the frequencies of actual
      respiratory symptoms. Forced expiratory volume in the first second (FEV1) was
      slightly lower in the farmers than in the pupils (p < 0.05). There was no
      difference in the prevalence of IgE-mediated allergy. Nine of the farmers but
      none of the pupils had precipitating antibodies against Faeni rectivirgula (p <
      0.05). Overall reactivity (as defined by at least one positive finding with the
      skin prick test, specific IgE, or precipitins) was associated with larger farming
      estates, lack of a haydrying device, use of mouldy hay, and positive family
      history of asthma (p < 0.05). We conclude that in farmers, precipitin formation
      may occur at an early age and that even in younger age groups there is a clear
      relationship between allergic sensitization and occupational allergen exposure.

PMID- 8859229
TI  - Decrease in CD23+ B lymphocytes and clinical outcome in asthmatic patients
      receiving specific rush immunotherapy.
AB  - Rush immunotherapy (RIT) has been documented as useful in the treatment of
      patients with allergic bronchial asthma. To investigate the mechanisms of its
      action, we studied changes in the serum levels of total IgE, allergen-specific
      IgE and IgG4, and expression of CD23 on peripheral blood B cells in patients
      receiving RIT. Twenty patients with perennial bronchial asthma were evaluated
      before the beginning of RIT, as well as 6 weeks and 6 months later. Compared to
      pretreatment values, the level of Der-p-specific IgG4 and IgE significantly
      increased after 6 weeks and 6 months of RIT, while the total serum IgE remained
      unchanged. Furthermore, after 6 months of RIT, the percentage of CD23+B cells and
      its CD23 receptor density significantly decreased. Since the symptom score
      improved and the need for medication decreased, we evaluated RIT as a useful
      procedure. After 6 months, 30% of patients did not have an asthma attack, with no
      medication in the last month, while 10% of them were asthma free for the last 3
      months. No significant correlation between the clinical improvement, and in vitro
      changes was found. Furthermore, the observed in vitro changes were not
      significantly different in patients who responded with clinical improvement,
      compared to those with unchanged intensity of asthma. In conclusion, during
      specific RIT we found a significant increase in Der-p-specific IgE and IgG4
      antibodies, as well as a moderate decrease in CD23+ B cells and its CD23 receptor
      density. These findings suggest a change in the lymphokine profile of patients
      receiving specific immunotherapy, and that the inhibition of IL-4-induced B cell
      stimulation may be hypothesized as the most important mechanism.

PMID- 8859231
TI  - Surviving in a risky business.

PMID- 8859230
TI  - Immunological analysis of organized pneumonia with eosinophilic pleural effusion.
AB  - A 73-year-old man developed organized pneumonia with severe right-sided
      eosinophilic pleural effusion (PE). CD69+ and HLA-DR+ eosinophils in PE were 90
      and 31%, respectively, but were undetectable in peripheral blood (PB). CD4+,
      CD45RA+ (naive) and CD4+, CD45RO+ (memory) cells in PB, PE and bronchoalveolar
      lavage (BAL) were 10.9, 8.4, 2.5 and 22.7, 38.3 and 16.4%, respectively. CD8+,
      CD45RA+ (naive) and CD8+, CD45RO+ (memory) cells in PB, PE and BAL were 3.5, 4.7,
      1.0, and 8.9, 11.3 and 46.0%, respectively. The concentrations of interleukin-5
      (IL-5) and IL-6 in PE were 1,680 and 2,797 pg/ml, respectively; however, these
      cytokines were undetectable in PB. The patient died 1 month after surgery to
      remove right thickened pleura. Microscopic findings showed right fibrinous
      pleuritis and organized pneumonia.

PMID- 8859233
TI  - Treatment of condylar hyperplasia of the mandible using unilateral ramus
      osteotomies.
AB  - PURPOSE: The long-term outcome of bilateral and unilateral ramus osteotomies used
      for the treatment of unilateral condylar hyperplasia of the mandible are
      evaluated and compared. MATERIALS AND METHODS: Thirteen cases of unilateral
      condylar hyperplasia of the mandible were surgically treated during a 10-year
      period from 1985 to 1995. Seven of the patients were treated by bilateral ramus
      osteotomies alone; six were treated by unilateral ramus osteotomies of the
      affected side. Unilateral ramus osteotomy was combined with a maxillary Le Fort I
      procedure in two of the six cases. Preoperative analysis of patients, indications
      for case selection, and postoperative results relating to facial symmetry,
      temporomandibular joint (TMJ) pain, occlusion, and stability were compared in the
      two groups. RESULTS: The postoperative findings and long-term results in both
      groups of patients were favorable. Symmetry, arch coordination, and occlusion
      remained stable. TMJ pain and dysfunction were invariably cured postoperatively.
      Unilateral ramus osteotomies alone, or in combination with maxillary surgery when
      deemed feasible and applicable by preoperative clinical analysis, was sufficient
      to restore symmetry and occlusion in dentally compensated cases. CONCLUSIONS:
      This study shows that patients with unilateral condylar hyperplasia of the
      mandible and deviation can be treated favorably by unilateral ramus osteotomy of
      the affected side; bilateral ramus osteotomy did not have any advantage in such
      cases. In addition, this procedure, combined with a Le Fort I osteotomy of the
      maxilla, was also effective in restoring occlusal canting and facial symmetry in
      dentally compensated cases. However, bilateral ramus osteotomy was required in
      prognathic cases and in cases in which a unilateral procedure would cause
      excessive rotation of the contralateral condyle.

PMID- 8859232
TI  - Clinical/biological outcomes of treatment for pericoronitis.
AB  - PURPOSE: This prospective clinical study was designed to determine the clinical
      and biologic outcomes of treatment for minor signs and symptoms of pericoronitis.
      PATIENTS AND METHODS: Patients (n = 20) with all third molars, presenting
      consecutively to an academic clinical center for treatment of minor signs and
      symptoms of pericoronitis, were enrolled in the study. At the initial visit,
      gingival crevicular fluid (GCF) samples to assess levels of the cytokines
      interleukin- 1b (IL-1b) IL-1b and prostaglandin E2 (PGE2) as a measure of the
      host inflammatory response, and plaque samples to identify microorganisms, were
      collected from the distal of all second molars and the mesial of first molars.
      Standardized vertical bite wing radiographs were taken to assess alveolar bone
      height on the distal of the second molars and the inclination and the degree of
      eruption of the third molar. Full-mouth periodontal probing was conducted to
      determine probing depths and relative clinical attachment levels (CAL). Pain
      levels were assessed with Gracely verbal descriptor scales for sensory intensity
      and unpleasantness and 10-cm visual analog scales. Symptomatic third molar sites
      were treated with local debridement and irrigation after baseline data
      collection. One week after entry, data were collected again. Subsequently, the
      patients were scheduled for removal of all third molars. Data collection was
      repeated 3 months postsurgery. As controls, data were collected from 12 subjects
      who had asymptomatic third molars removed previously. RESULTS: At entry,
      symptomatic mandibular third molars (n = 21) were mostly vertical (n = 18) and at
      or above the occlusal plane (n = 19). No maxillary teeth had symptoms. Microbial
      counts were elevated for specific anaerobic microorganisms. GCF IL-1b levels were
      elevated at the distal of second molars adjacent to symptomatic third molars, as
      compared with asymptomatic third molars and second molars in control patients.
      Alveolar bone levels and CAL on the distal of second molars were normal. At 1
      week, patients' pain symptoms and IL-1b levels were reduced, but microbial counts
      remained high. Three months after surgery, patients had no pain symptoms, and
      alveolar bone levels and CAL were similar to entry levels. IL-1b levels were
      elevated at both the distal of second molars and the mesial of first molars for
      all patients; microbial counts decreased, although not to levels of control
      patients. No increase in microbial counts for Porphyromonas gingivalis or
      Bacteroides forsythus, or GCF PGE2 levels, risk factors for progressive
      periodontal disease, was detected in samples taken from the study patients.
      CONCLUSION: Pericoronitis expressed by minor signs/symptoms in these patients was
      associated with considerable discomfort. Symptomatic mandibular third molars were
      vertical and at or near the occlusal plane. Additionally, this condition was
      characterized by microbial flora and GCF inflammatory mediator levels that are
      more consistent with gingivitis than periodontitis. Removal of third molars
      eliminated symptoms, but the microbial burden and an affected patient's
      inflammatory response, as measured by IL-1b levels, remained elevated as compared
      with controls. Further study is needed to determine which of these factors can be
      used to identify patients at risk for pericoronitis before symptoms arise.

PMID- 8859235
TI  - Surgical management of pleomorphic adenomas of the parotid gland: a follow-up
      study of three methods.
AB  - PURPOSE: This retrospective study evaluated data pertaining to history, symptoms,
      diagnosis, and mode of therapy of patients treated for pleomorphic adenoma of the
      parotid gland. PATIENTS AND METHODS: The records of 475 patients were reviewed.
      Follow-up was done by questionnaires sent to the referring doctor. RESULTS: The
      total rate of recurrence was 0.9% after 475 operations for pleomorphic adenoma of
      the parotid gland. One recurrence (0.7%) was reported for the group with
      superficial parotidectomy and none for the group with total parotidectomy. The
      rate of postoperative side effects was also low. The facial nerve was affected in
      1.4% after superficial parotidectomy, and in 3.3% after total parotidectomy.
      CONCLUSION: The results of this follow-up study show that superficial
      parotidectomy for pleomorphic adenoma located in the superficial lobe of the
      parotid gland provides adequate therapy and generally avoids recurrence and side
      effects.

PMID- 8859236
TI  - Augmentation of localized defects of the anterior maxillary ridge with autogenous
      bone before insertion of implants.
AB  - PURPOSE: This study evaluated the applicability of intraorally harvested
      autogenous bone grafts for the augmentation of the narrow maxillary alveolar
      ridge to enable insertion of implants for single tooth replacement. MATERIALS AND
      METHODS: Local defects of the anterior maxilla were reconstructed in 27 patients
      with autogenous bone grafts from the mandibular symphysis (n = 12), maxillary
      tuberosity (n = 8), or mandibular retromolar area (n = 7). Three months after
      grafting, either Branemark (n = 23) or ITI Bonefit implants (n = 8) were
      inserted. RESULTS: At the time of implantation, all grafted sites showed
      sufficient bone volume for insertion of the implants. Twenty-four to 68 months
      after insertion, all implants were functioning well. CONCLUSION: Augmentation of
      local alveolar defects in the maxilla with intraorally harvested autogenous bone
      grafts appears to be a reliable method to enable implant placement.

PMID- 8859234
TI  - The effect of a 4-mg preoperative intravenous dose of ondansetron in preventing
      nausea and vomiting after maxillofacial surgery.
AB  - PURPOSE: The efficacy of a preoperative 4-mg dose of ondansetron given
      intravenously in preventing postoperative nausea and vomiting after maxillofacial
      surgery was evaluated in a double-blind randomized study. PATIENTS AND METHODS:
      Sixteen patients had intravenous ondansetron, and an equal number had normal
      saline as a placebo immediately before induction of anesthesia. After intubation,
      a nasogastric tube was inserted, and general anaesthesia was induced with
      thiopentone, suxamethonium, fentanyl, nitrous oxide, enflurane, and vecuronium.
      Anesthesia lasted more than 1 hour in all patients. Postoperatively, episodes of
      vomiting were recorded, and nausea was assessed on a visual analog scale at 1, 4,
      and 24 hours from the time of awakening. RESULTS: Eight patients in the
      ondansetron group, compared with six in the placebo group, had nausea, and six in
      the ondansetron group and three in the placebo group vomited. Of the six patients
      who vomited in the ondansetron group, five vomited more than 8 hours from the
      injection of ondansetron. No significant adverse effects could be directly
      attributable to ondansetron. CONCLUSION: Four milligrams ondansetron given
      intravenously preoperatively was ineffective in controlling postoperative nausea
      and vomiting after maxillofacial surgery. Possibly, a larger dose or a second
      dose given 8 hours after the first dose may be effective.

PMID- 8859237
TI  - Effects of sedation with midazolam or propofol on cognition and psychomotor
      functions.
AB  - PURPOSE: The study compared the effects of midazolam and propofol on explicit and
      implicit memory, cognition, and psychomotor function in patients undergoing oral
      surgical procedures with local anesthesia and conscious sedation. METHODS: Twenty
      eight patients were tested in a randomized, double-blind study. Patients were
      randomly allocated to one of two groups. One group received a bolus dose of
      midazolam, 0.1 mg/kg, followed by a continuous infusion of saline. The other
      group received a bolus dose of propofol, 1.0 mg/ kg, followed by a continuous
      infusion of propofol, 65 micrograms/kg/min. Subjective rating questionnaires and
      tapping, memory, and Digit Symbol Substitution tests were administered. Testing
      was done at baseline, 10 minutes after the drugs were given, 10 minutes after
      surgery ended and 10 minutes later. RESULTS: The midazolam and propofol groups
      did not differ significantly on any demographic variables. Both drugs produced
      mental and physical sedation, which did not become substantially attenuated
      during the time studied. Both tranquilization and attitudes or other feelings
      showed smaller drug effects than mental and physical sedation. Tapping was
      decreased by both drugs 10 minutes after treatment, but not postsurgery.
      Performance on the Digit Symbol Substitution test was below baseline levels for
      both drugs at 10 minutes after treatment, but only for midazolam in the
      postsurgery assessment; at 10 minutes after treatment, propofol was associated
      with poorer performance than midazolam. Immediate and delayed explicit recall
      were impaired by both drugs 10 minutes after treatment. Immediate and delayed
      recall were lower for midazolam than propofol postsurgery, but only the
      difference on immediate recall was significant. Implicit memory was spared by
      both drugs. CONCLUSIONS: Midazolam and propofol generally produced equivalent
      impairments, but the duration of the effects of propofol was shorter. Unlike
      explicit memory, implicit memory resisted impairment.

PMID- 8859238
TI  - Diffuse sclerosing osteomyelitis of the mandible: its characteristics and
      possible relationship to synovitis, acne, pustulosis, hyperostosis, osteitis
      (SAPHO) syndrome.
AB  - PURPOSE: This article reports on the possible relationship of diffuse sclerosing
      osteomyelitis (DSO) of the mandible to synovitis, acne, pustulosis, hyperostosis,
      osteitis (SAPHO) syndrome. PATIENTS AND METHODS: The pathologic features in 12
      new DSO patients and those in previously reported cases were reviewed and
      compared with those of SAPHO syndrome. RESULTS: Many similarities were noted
      between the two entities in terms of the clinical, radiographic, and histologic
      features. Furthermore, multiple bone lesions and skin lesions (palmoplantar
      pustulosis and psoriasis) were observed not only in SAPHO syndrome but also in
      DSO patients. CONCLUSION: DSO is concluded to be one manifestation of SAPHO
      syndrome.

PMID- 8859239
TI  - The effect of ovariectomy on the temporomandibular joints of growing rats.
AB  - PURPOSE: This investigation studied the effects of ovariectomy, on the
      temporomandibular joints (TMJ) of young rats. MATERIALS AND METHODS: Four-week
      old female Wistar rats were ovariectomized and killed at the intervals of 1, 2,
      4, and 8 weeks postoperatively. Histomorphometric study of the TMJ was performed
      in a synchronous manner with an age-matched sham-operated control group. The
      serum levels of estrogen, calcitonin, and C-terminus parathyroid hormone were
      also determined. RESULTS: In the sham-operated control group, the serum levels of
      estrogen and calcitonin increased with age. An increase of the bone volume, with
      a concomitant increase of the osteoid surface, was observed at 12 weeks.
      Thickness of the articular soft tissue was decreased with increasing age. In the
      ovariectomized animals, serum estrogen was not detected during the experiment. A
      biphasic change in the parathyroid hormone level, with decreases at 1 and 2 weeks
      after the ovariectomy and increases at 4 and 8 weeks postoperatively, was
      observed, whereas a constant value was noted in the calcitonin level. Thickness
      of the articular soft tissue was increased in the anterior and central portions
      of the condyle at 1, 2, and 4 weeks after the ovariectomy, whereas no appreciable
      changes were observed in the posterior portion. The bone volume was decreased
      during the experiment, particularly in the posterior portion. An osteophyte in
      the anterior region was also observed 8 weeks postoperatively. CONCLUSIONS:
      Estrogen deficiency in rats during puberty predisposes to alterations of the TMJ
      through changes in serum calcitonin and parathyroid hormone levels.

PMID- 8859240
TI  - In vivo testing of an experimental endosseous implant design.
AB  - PURPOSE: The purpose of this study was to test a new implant system with apically
      expanding, double-hinged wing stabilizers in dogs before human testing. METHODS:
      Twenty-seven HA-coated endosseous implants were placed in five dog mandibles. The
      implants were placed into function for 12-weeks after a 12-week healing period.
      At the end of this period, the implants were evaluated clinically and
      radiographically. The animals then were killed, allowing for the implants to be
      evaluated mechanically and histologically. RESULTS: After the initial healing
      period, 24 of 27 implants demonstrated osseointegration. Seven of eight implants
      restored with acrylic resin-fixed partial dentures were stable after the 12-week
      period of function. However, 17 of 27 implants failed to satisfactorily deploy
      the apical wing stabilizer system. CONCLUSION: This new implant system has a
      number of design flaws that must be addressed before testing in humans.

PMID- 8859241
TI  - Histologic evaluation of auricular cartilage grafts after discectomy in the
      rabbit craniomandibular joint.
AB  - PURPOSE: The clinical use of auricular cartilage grafting after discectomy has
      been reported as a treatment in the terminal stage of internal derangement of the
      temporomandibular joint (TMJ). Although the occurrence of fibrous adhesions has
      been observed in such grafted joints, the exact tissue reaction to the graft is
      still not understood. The purpose of this study was to evaluate the histologic
      changes after discectomy and auricular cartilage grafting in the rabbit
      craniomandibular joint (CMJ). MATERIALS AND METHODS: Unilateral discectomy of the
      left CMJ was performed in 28 Japanese white rabbits. Auricular cartilage
      harvested from the ipsilateral ear was grafted as a disc replacement in 14
      animals (Group C), and the other 14 underwent wound closure immediately after
      discectomy (Group B). Two other rabbits (Group A) served as nonsurgically treated
      controls. Two rabbits from each experimental group were killed at 2, 4, 6, 8, 10,
      12, and 24 weeks postoperatively. Microscopic observation of the specimens was
      performed in the parasaggital plane. RESULTS: Complete resorption of the
      cartilage layer on the articular surface was observed within 4 weeks
      postoperatively in group B. Regeneration of a fibrous cartilage layer was
      observed in this group after 6 weeks, but the postoperative degenerative changes
      were so severe that the surface of the condyle and eminence was flattened. In
      contrast, the degenerative changes were milder in group C, although the grafted
      cartilage showed perforation and fragmentation from the sixth postoperative week
      onward. The condylar shape and cartilage layer were well preserved at all times.
      CONCLUSIONS: These results suggest that the structure and function of the condyle
      may be preserved by auricular cartilage grafting after discectomy. However, the
      problems of adhesion and fragmentation need to be addressed.

PMID- 8859242
TI  - Recognition of the scope of oral and maxillofacial surgery by the public and
      health care professionals.
AB  - PURPOSE: A recent British study has reported a lack of awareness among the
      general public as to the benefits provided by the specialty of oral and
      maxillofacial surgery (OMFS). Medical and dental practitioners surveyed had a
      greater awareness of OMFS than the general public, yet were deficient in
      knowledge of the wide range of services provided by them. Therefore, a similar
      survey was conducted in the Boston area to determine the awareness among the
      general public and health professionals of the proper providers of treatment for
      the maxillofacial region and the level of knowledge of the specialty of OMFS.
      MATERIALS AND METHODS: The study incorporated five groups of respondents: dental
      students, dental practitioners, medical students, medical practitioners, and the
      general public. The survey was mailed, or distributed, randomly to persons
      representing each group in the Boston area. Between 200 and 300 surveys were sent
      to each group, and data collection was stopped at 100 responses per group.
      Surveys from the general public were screened to eliminate responders involved in
      health professions. For each of 20 specific situations or treatments, respondents
      were asked to choose a source of treatment from among four categories of
      specialists: ear nose and throat surgery (ENT), plastic surgery, OMFS, and
      periodontology. A chi-square analysis was performed for each question to compare
      the pattern of responses among categories of respondents. RESULTS: The data
      showed that most of the health professionals, 90% of students, and 98% of
      practitioners had heard of OMFS, whereas only 62% of the public have heard of
      this specialty. Furthermore, only 22% of the lay responders had ever been treated
      by an OMFS. The results also suggested that many health professionals had a lack
      of understanding about the wide scope of surgical procedures that OMFSs offer.
      CONCLUSION: Despite all the progress that has occurred in OMFS, a large portion
      of the American population is still unaware of the specialty. If patients are to
      receive the best treatment available, it is essential to educate health care
      consumers and providers about the different specialties available and their role
      within the health profession.

PMID- 8859243
TI  - Trismus and preauricular swelling in a 20-year-old black woman.

PMID- 8859244
TI  - Extraction of a horizontally impacted mandibular canine through a genioplasty
      approach: report of a case.

PMID- 8859245
TI  - Central mucoepidermoid carcinoma of the mandible: report of a case treated 13
      years after first radiographic demonstration.

PMID- 8859246
TI  - Dysgenetic polycystic disease of the parotid gland: report of case.

PMID- 8859247
TI  - Desmoplastic fibroma of the mandible: review and report of two cases.

PMID- 8859248
TI  - A device for measuring bone thickness in relation to dental implants.

PMID- 8859249
TI  - A transoral approach for three-dimensional repositioning of the proximal segment
      after mandibular sagittal split ramus osteotomy.

PMID- 8859250
TI  - Use of methohexital in cardiac patients.

PMID- 8859251
TI  - Injury prevention and the pediatrician.

PMID- 8859252
TI  - Centers for Disease Control and Prevention guidelines for congenital syphilis.

PMID- 8859253
TI  - Neonatology in the 1990s and beyond.

PMID- 8859254
TI  - Do the Framingham Safety Surveys improve injury prevention counseling during
      pediatric health supervision visits?
AB  - BACKGROUND: Previous studies suggest that injury prevention counseling by
      pediatricians is effective but accomplished infrequently. The Framingham Safety
      Surveys (FSS) are brief questionnaires designed to facilitate physician education
      of parents regarding injury prevention. OBJECTIVE: To determine whether the FSS
      improve pediatricians' injury prevention counseling. DESIGN: Nonrandomized
      comparison of a 4-week baseline period and subsequent intervention periods.
      SETTINGS: Private practice; university hospital clinic. PATIENTS: Patients coming
      for health supervision visits. INTERVENTION: Provision to the physician of one of
      the FSS, completed by the parent just before the health supervision visit.
      OUTCOME MEASURES: (1) After each visit parents completed a checklist of safety
      issues discussed by the pediatrician. Injury prevention was compared for the two
      periods by means of three criteria: number of issues discussed (quantity),
      identification and discussion of specific high-risk behaviors (efficiency), and
      recognition of high-risk families (targeting). (2) Each physician's assessment of
      the value of the FSS was obtained by questionnaire. RESULTS: A total of 144
      parents (50 from the private practice, 94 from the clinic) completed checklists
      during the baseline period, and 168 (38 from the private practice, 130 from the
      clinic) during the intervention period. Use of the FSS produced no detectable
      improvement in any of the three measures. Seventy-seven percent of the physicians
      indicated that the FSS were helpful in educating families about safety, 38%
      thought that the FSS helped identify high-risk families, and 54% said they would
      use it again. CONCLUSIONS: Although most physicians believed the FSS were useful,
      introduction of the surveys as employed in this study did not improve injury
      prevention counseling.

PMID- 8859255
TI  - Problems in the current case definitions of congenital syphilis.
AB  - During the course of a population-based epidemiologic study of congenital
      syphilis, we found discrepancies and problems of validity in the case definitions
      of congenital syphilis of the Centers for Disease Control and Prevention and
      other experts. We analyzed these problems and determined their impact on case
      classification in our study. The most important problem that we found was the
      case definitions' lack of a valid scientific basis for the classification of
      symptom-free infants born to mothers who have been treated for syphilis but have
      uncertain infection status (286 infants in our study). The classification of
      these infants is based on diagnostic tests whose sensitivity and specificity are
      unknown. In our study, we found that results of some tests were rarely positive
      and that values for others were similar to those in uninfected infants. We
      believe that symptom-free infants of treated mothers of uncertain infection
      status should be classified as cases, pending the development of better
      diagnostic tests for congenital syphilis. The economic impact of treating these
      infants can be lessened by obtaining fewer diagnostic tests and by use of one
      injection of penicillin rather than a 10- to 14-day course, an approach suggested
      by a literature review. Use of infants' diagnostic tests to classify any other
      group of symptom-free infants does not seem appropriate, even though this is
      often recommended.

PMID- 8859256
TI  - Relationship between blood pressure and cardiac output in preterm infants
      requiring mechanical ventilation.
AB  - OBJECTIVE: To assess the contribution of cardiac output in determining the blood
      pressure of preterm infants and to identify other factors that may be important.
      METHODS: Sixty-seven preterm infants requiring mechanical ventilation (median
      birth weight, 1015 gm: median gestational age, 28 weeks) underwent on
      echocardiographic study at on average age of 19 hours (range, 7 to 31 hours).
      Measurements taken included left ventricular ejection fraction, left and right
      ventricular outputs by means of pulsed Doppler and the diameter of both the
      ductal and atrial shunt jets with the use of color Doppler as a measure of the
      size of shunt. Simultaneous measurements of intraarterial blood pressures, mean
      airway pressure, and inspired fraction of oxygen were recorded. RESULTS: After we
      allowed for the influence of ductal shunting, the correlation between the left
      ventricular output and mean arterial blood pressure was significant but weak (r =
      0.38). There were infants with low blood pressures and normal cardiac outputs,
      and conversely there were infants with low cardiac outputs and normal blood
      pressure. The infants with a mean arterial blood pressure of less than 30 mm Hg
      had a significantly lower gestational age (27 vs 28 weeks), higher mean airway
      pressure (9.0 vs 7.0 cm H2O), larger ductal diameter (1.6 mm vs 0.7 mm) and a
      lower systemic vascular resistance (163 vs 184 mm Hg/L per minute per kilogram of
      body weight). Multilinear regression identified higher mean airway pressure and
      larger ductal diameter as significant negative influences on mean arterial blood
      pressure, with higher gestational age and higher left ventricular output as
      significant positive influences. CONCLUSIONS: Normal blood pressure cannot
      necessarily be equated with normal systemic now. These data emphasize the
      importance of other influences, and in particular that of varying systemic
      vascular resistance, in the determination of blood pressure in preterm infants.

PMID- 8859257
TI  - Seasonal onset of systemic-onset juvenile rheumatoid arthritis.
AB  - OBJECTIVE: This study was undertaken to investigate the recent finding of a
      seasonal difference in the onset of systemic-onset juvenile rheumatoid arthritis
      (SoJRA). We hypothesized that a seasonal onset pattern might implicate on
      infectious agent as a cause of SoJRA. METHODS: The date of onset was collected
      from the records of all patients with SoJRA from 1980 to 1992 at presentation to
      pediatric rheumatology clinics across Canada. The onset pattern of SoJRA was then
      compared with incidence data on viral infections obtained for the same period.
      RESULTS: Across Canada the onset of SoJRA was constant across the seasons.
      However, in the Prairie region there was a statistically significant seasonal
      pattern, with peaks in autumn and early spring. We could find no evidence that
      viral incidence correlated with disease incidence either throughout Canada or in
      the Prairie region. CONCLUSIONS: If a seasonal infectious agent causes SoJRA,
      then it is likely only one of several causes and may act only in certain regions.
      Future studies should be carried out in those areas where SoJRA does have a
      seasonal onset pattern.

PMID- 8859258
TI  - Impaired response to furosemide in hyperprostaglandin E syndrome: evidence for a
      tubular defect in the loop of Henle.
AB  - In hyperprostaglandin E syndrome (HPS) renal wasting of electrolytes and water is
      consistently associated with enhanced synthesis of prostaglandin E2. In contrast
      to Bartter or Gitelman syndrome (BS/GS), HPS is characterized by its severe
      prenatal manifestation, leading to fetal polyuria, development of polyhydramnios,
      and premature birth. This disorder mimics furosemide treatment with hypokalemic
      alkalosis, hypochloremia, isosthenuria, and impaired renal conservation of both
      calcium and magnesium. Therefore the thick ascending limb of the loop of Henle
      seems to be involved in HPS. To characterize the tubular defect we investigated
      the response to furosemide (2 mg/kg) in HPS (n = 8) and BS/GS (n = 3) 1 week
      after discontinuation of long-term indomethacin treatment. Sensitivity to
      furosemide was completely maintained in patients with BS/GS. The diuretic,
      saluretic, and hormonal responses were similar to those of a control group of
      healthy children (n = 13), indicating an intact function of the thick ascending
      limb of the loop of Henle in BS/GS. In contrast, patients with HPS had a marked
      resistance to this loop diuretic. Furosemide treatment increased urine output by
      7.5 +/- 0.7 ml/kg per hour in healthy control subjects but only by 4.4 +/- 1.2
      ml/kg per hour (p < 0.5) in children with HPS. In parallel, the latter also had a
      markedly impaired saluretic response (delta Cl(urine) 0.14 +/- 0.04 mmol/kg per
      hour vs 0.85 +/- 0.09 mmol/kg per hour, p < 0.001; delta Na(urine) 0.23 +/- 0.06
      mmol/kg per hour vs 0.77 +/- 0.09 mmol/kg per hour, p < 0.001). Furosemide
      therapy further enhanced prostaglandin E2 excretion in patients with HPS (54 +/-
      17 to 107 +/- 28 ng/hr per 1.73 m2, p < 0.05), whereas no significant effect was
      observed in healthy children (20 +/- 3 to 12 +/- 3 ng/hr per 1.73 m2). We
      conclude that a defect of electrolyte reabsorption in the thick ascending limb of
      the loop of Henle plays a major role in HPS.

PMID- 8859259
TI  - Children hospitalized for varicella: a prevaccine review.
AB  - OBJECTIVES: To describe varicella complications in healthy and previously ill
      children hospitalized for varicella and to explore trends in group A beta
      hemolytic streptococcus complications of varicella. METHODS: A retrospective
      record review of children hospitalized for varicella between January 1, 1990, and
      March 31, 1994, was conducted in nine large acute care hospitals in Los Angeles
      County, California. RESULTS: We identified 574 children hospitalized for
      varicella in study hospitals during the 4.25-year study period (estimated risk of
      hospitalization, approximately 1 in 550 cases of varicella); 53% of the children
      were healthy before the onset of varicella and 47% were previously ill with
      underlying cancers or other chronic illnesses. Children were hospitalized for
      treatment of complications (n = 427, 74%) or for prophylactic antiviral therapy
      or observation (n = 147, 26%). Systems involved in complications included
      skin/soft tissue (45%), neurologic (18%), respiratory (14%), gastrointestinal
      (10%), and hematologic, renal, or hepatic (8% or less). The mean age of children
      with skin/soft tissue infections was 2.7 years (range < 1 to 16 years) compared
      with 4.7 years (< 1 to 18 years) for other complications. Children with skin/soft
      tissue and neurologic complications were more often previously healthy (p <
      0.05), whereas those with respiratory complications were more often previously
      ill (p < 0.001). Hospitalizations for skin/soft tissue infections increased
      during the study period. The proportion of complications as a result of group A
      beta-hemolytic streptococcus infection increased from 4.7% before 1993 to 12.2%
      for the remainder of the study period (p = 0.02). CONCLUSIONS: Prior health
      status was predictive of the type of complications experienced by children with
      varicella requiring hospitalization. Our data suggest a recent increase in
      skin/soft tissue complications of varicella requiring hospitalization and an
      increase in the proportion of complications related to group A beta-hemolytic
      streptococcus. Wide-scale vaccine use should reverse this trend and reduce the
      overall impact of varicella on both healthy and previously ill children.

PMID- 8859260
TI  - Effect of exercise training on energy expenditure, muscle volume, and maximal
      oxygen uptake in female adolescents.
AB  - OBJECTIVES: American female adolescents are at high risk of a physically inactive
      lifestyle that likely leads to health problems later in life. We hypothesized
      that a brief program of endurance exercise training in female adolescents would
      result in increased energy expenditure and quantifiable structural and functional
      adaptations. STUDY DESIGN: Forty-four high school girls (aged 15 to 17 years,
      none were elite athletes) enrolled in a 5-day per week anatomy class for 5 weeks
      and were randomly assigned to control (n = 22) and training groups. All subjects
      participated in a 2-hour daily teaching program. During the remaining time (2
      hours), the training group members underwent endurance-type training and control
      group subjects participated in a computer workshop. The intervention was assessed
      by (1) comparison of total energy expenditure between groups with the doubly
      labeled water technique, (2) determination of changes in thigh muscle volume by
      magnetic resonance imaging, and (3) determination of changes in maximal oxygen
      uptake by use of respiratory gas exchange responses. RESULTS: Total energy
      expenditure was significantly greater (15.3%) in the training group compared with
      the control subjects (p < 0.003). Five weeks of training led to a 4.3% +/- 1%
      increase in thigh muscle volume (p < 0.0002) and a 12.1% +/- 3.7% increase in
      maximal oxygen uptake (p < 0.004); there were no changes in the control group.
      The training effect was most pronounced in the least fit subjects. CONCLUSIONS:
      Exercise training programs for female adolescents can be successfully integrated
      into a high school summer curriculum. Quantifiable, substantial structural and
      functional responses occur with relatively short periods of training.
      Approximately 60% of the training response was related to factors independent of
      muscle size per se. These data may serve to better design physical activity
      programs for female adolescents.

PMID- 8859261
TI  - Final height and hormonal function after bone marrow transplantation in children.
AB  - AIM: To analyze final height and hormonal function in long-term survivors of bone
      marrow transplantation (BMT). PATIENTS: Group 1 consisted of 16 patients (10
      boys) with a hematologic malignancy, mostly leukemia, conditioned for BMT with
      total body irradiation (TBI), 7.5 to 12 Gy, and cyclophosphamide. Group 2
      consisted of 14 patients (9 boys) with severe aplastic anemia, conditioned with
      chemotherapy only. RESULTS: In group 1, patients achieved a reduced final height
      after BMT. The difference between the height standard deviation score (SDS) at
      BMT and the height SDS at final height was -1.96 (0.82) SDS in boys and -0.92
      (0.71) SDS in girls (p = 0.0001, and p = 0.02 respectively). Final height was
      also lower than target height (boys, p = 0.01; girls, p = 0.03). Prepubertal
      growth in the first 3 years after BMT was normal but pubertal height gain was
      decreased. The patients in group 2 achieved normal height. Thyroid function and
      adrenal function were normal in all patients, and no growth hormone deficiency
      was detected. Serum follicle-stimulating hormone values after BMT were increased
      in all group 1 patients, with return to normal in two patients. Serum luteinizing
      hormone values were increased in all group 1 girls, with recovery in one girl.
      Normal serum luteinizing hormone values and spontaneous puberty were found in all
      group 1 boys. In group 2, disturbances in gonadotropins were seen only in three
      boys and two girls. CONCLUSION: In patients treated in childhood with BMT after
      chemotherapy and TBI with 7.5 Gy or more, final height is compromised because of
      blunted growth in puberty. Patients who had not received TBI suffered no height
      loss. In the majority of patients, the combination of chemotherapy and TBI also
      resulted in irreversible disturbances of gonadal function.

PMID- 8859262
TI  - Low-dose recombinant human granulocyte colony-stimulating factor therapy in
      children with symptomatic chronic idiopathic neutropenia.
AB  - OBJECTIVES: To prospectively define the lowest possible doses of recombinant
      human granulocyte colony-stimulating factor (rhG-CSF) that would benefit selected
      children with chronic idiopathic neutropenia whose disease was severe enough to
      interfere appreciably with quality of life. STUDY DESIGN: The efficacy of low
      dose rhG-CSF therapy was investigated in six children with symptomatic chronic
      idiopathic neutropenia. All patients received rhG-CSF, 5 micrograms/kg
      subcutaneously, as a single daily dose until an absolute neutrophil count (ANC)
      above 1.5 x 10(9)/L was observed. The rhG-CSF dosage interval and amount were
      then increased and decreased, respectively, in an alternating fashion until the
      lowest rhG-CSF dose that would maintain the ANC above 1.0 x 10(9)/L (1000/mm3)
      was reached. RESULTS: Although the minimal dose requirements varied, all patients
      were able to maintain a mean ANC > 1.0 x 10(9)/L during a mean follow-up period
      of 14 months at doses ranging from 1.0 microgram/kg once weekly to 5.0
      micrograms/kg every other day. Administration of rhG-CSF resulted in resolution
      of all preexisting chronic infections, reduction in the frequency of new
      infectious episodes, and discontinuation of prophylactic antibiotics. In all
      patients the ANC decreased to pretreatment values when further reduction or
      discontinuation of rhG-CSF therapy was attempted. By identifying the minimal
      effective dose in each patient, we were able to reduce the treatment cost by a
      mean of 81% compared with daily dosage at 5 micrograms/kg. CONCLUSIONS:
      Recombinant human granulocyte colony-stimulating factor therapy at low doses (<
      or = 5 micrograms/kg) every 2 to 7 days to symptomatic children with chronic
      idiopathic neutropenia is effective and no more costly than supportive treatment
      with antibiotics.

PMID- 8859263
TI  - Clinical and hematologic effects of hydroxyurea in children with sickle cell
      anemia.
AB  - PURPOSE: This open-label pilot study was designed (1) to determine the effect of
      hydroxyurea on the hemoglobin level in children with sickle cell anemia, (2) to
      evaluate the toxicity of hydroxyurea, and (3) to assess any impact of hydroxyurea
      on the frequency of vaso-occlusive crises (VOCs). PATIENTS AND METHODS: Ten
      children (group 1) with three or more VOCs of the extremities or two or more VOCs
      of the lungs (acute chest syndrome) in the preceding 12 months, and five children
      (group 2) with hemoglobin levels less than 70 gm/L were treated with hydroxyurea
      in doses of 20 to 35 mg/kg per day. The frequency of VOCs before hydroxyurea
      therapy was compared with the frequency during therapy, and the peak hemoglobin
      levels during hydroxyurea therapy were compared with the pretreatment values.
      RESULTS: One patient in group 1 was removed from the study within 1 month because
      of nausea. Seven of the remaining nine patients in group 1 had a decrease in the
      frequency of VOCs. The number of VOCs per patient-year for all 14 patients
      decreased from 2.5 before hydroxyurea therapy to 0.87 during hydroxyurea therapy,
      a decrease of 65% (p < 0.00001). Two of five patients in group 2 had an increase
      in hemoglobin of 27 gm/L and 34 gm/L over the baseline. The median rise in
      hemoglobin was 19 gm/L (range, 7 to 37) for all 14 patients. Nine patients are
      still receiving hydroxyurea for a median period of 23 months (range, 18 to 59).
      CONCLUSIONS: Hydroxyurea decreases the severity of anemia in some patients, and
      it may decrease the frequency of VOC. Its short-term hematologic toxicity is
      minimal.

PMID- 8859264
TI  - High-frequency pressure-control ventilation with high positive end-expiratory
      pressure in children with acute respiratory distress syndrome.
AB  - OBJECTIVE: Animal models suggest that high-frequency ventilation with low tidal
      volumes and high positive end-expiratory pressure (PEEP) minimize secondary
      injury to the lung. We hypothesized that using a high-frequency pressure-control
      mode of ventilation with high PEEP in children with severe acute respiratory
      distress syndrome (ARDS) would be associated with improved survival. DESIGN: The
      study was a retrospective and prospective clinical study at a 24-bed tertiary
      care pediatric critical care unit. Fifty-three patients with severe ARDS were
      studied during a 37-month period, 30 prospectively and 23 retrospectively. Severe
      ARDS was defined as (1) rapid onset of severe bilateral infiltrates of noncardiac
      origin, (2) partial pressure of oxygen (arterial)/fraction of inspired oxygen
      less than 200 on PEEP of 6 cm H2O or more for 24 hours or longer, and (3) Murray
      disease severity score greater than 2.5. All patients meeting these criteria
      underwent ventilation in the pressure-control mode; the protocol for ventilation
      had the following general guidelines: (1) fraction of inspired oxygen limited to
      0.5, (2) mean airway pressure titrated with PEEP to maintain arterial partial
      pressure of oxygen of 55 mm Hg or greater (7.3 kPa), (3) peak inspiratory
      pressure minimized to allow hypercapnia (arterial partial pressure of carbon
      dioxide, 45 to 60 mm Hg (6.0 to 8.0 kPa), and (4) ventilator rates of 40 to
      120/min. Percutaneous thoracostomy and mediastinal tubes were placed for
      treatment of air leak. RESULTS: The survival rate was 89% (47/53) in children
      with severe ARDS. Nonsurvivors had significantly higher peak inspiratory
      pressures (75 vs 40 cm H2O, p = 0.0006), PEEP (23 vs 17 cm H2O, p = 0.0004), mean
      airway pressure (40 vs 28 cm H2O, p = 0.04), alveolar-arterial oxygen gradient
      (579 vs 540 mm Hg, p = 0.03), and oxygenation index (43 vs 19, p = 0.0008) than
      survivors. Air leak was present in 51% of patients; there was no difference in
      the incidence of air leak between survivors and nonsurvivors (p = 0.42).
      CONCLUSIONS: The high-frequency positive-pressure mode of ventilation was safe
      and was associated with an improved survival rate (89%) for children with severe
      ARDS. Limitation of both inspired oxygen and tidal volume, along with aggressive
      treatment of air leak, may have contributed to the improved survival rate.

PMID- 8859265
TI  - Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for
      early diagnosis of neonatal infection.
AB  - OBJECTIVE: To evaluate plasma levels of interleukin-6 (IL-6) and soluble tumor
      necrosis factor receptors (sTNF-R) 55 and 75 in neonates as a contribution to the
      early diagnosis of infection. STUDY DESIGN: We prospectively measured IL-6 and
      sTNF-R 55 and sTNF-R 75 plasma levels in 157 newborn infants admitted to our
      regional neonatal center in a 3-month period and in cord blood of 131 newborn
      infants delivered in our obstetrics unit. C-reactive protein was sequentially
      determined after admission. Newborn infants were classified into four groups:
      group 0, not infected; group 1, possibly infected; group 2a, infected (culture
      positive), and group 2b, probably infected (culture negative). We looked for the
      optimal cutoff point of these parameters, using the receiver operating
      characteristics (ROC) curve. RESULTS: IL-6 levels were significantly higher in
      group 2 (n = 11; median level, 250 pg/ml; range, 0 to 81,000), group 2b (n = 25;
      median level, 750 pg/ml; range, 0 to 180,000), and group 1 (n = 35; median level,
      160 pg/ml; range 0 to 10,000), in comparison with group 0 (n = 217; median level,
      0 pg/ml; range, 0 to 3400). A cutoff value of 100 pg/ml or greater obtained by
      the ROC method gives a sensitivity of 83.3% and a specificity of 90.3%. For
      inborn infants (n = 220) sampled at birth, sensitivity is 100% and specificity
      92.3%. This high sensitivity persists until the twelfth hour of life. The sTNF-R
      55 levels are significantly higher in group 2a (median, 12.0 ng/ml; range, 3.2 to
      24.4). In group 2b (median, 7.0 ng/ml; range, 3.0 to 25.2), and in group 1
      (median, 7.0 ng/ml; range, 2.5 to 18.9) than in group 0 (median, 3.9 ng/ml;
      range, 1.5 to 15.0), and with a cutoff value of 6 ng/ml, sensitivity is 75% and
      specificity 69%. The sTNF-R 75 levels are significantly higher in group 2a
      (median, 17.0 ng/ml; range, 7.2 to 48.8). In group 2b (median, 11.2 ng/ ml;
      range, (2.0 to 31.3), and in group 1 (median, 10.6 ng/ml; range, 2.0 to 33.0);
      than in group 0 (median, 7.0 ng/ml; range, 1 to 23.0). With a cutoff value of 9
      ng/ ml, sensitivity is 80% and specificity 67%. Sensitivity of C-reactive protein
      is low initially but improves with time. Combining IL-6 with C-reactive protein
      provides the possibility of identifying the majority of infected infants in the
      postnatal period. CONCLUSION: A plasma IL-6 level of 100 pg/ml or greater,
      obtained before the twelfth hour of life, appears to be an ideal marker for
      detecting early-onset neonatal infection with a high degree of sensitivity and
      specificity. After the twelfth hour, the combined determination of IL-6 and C
      reactive protein may be equally useful. The sTNF-R levels appear to be less
      useful in the early diagnosis of infection because of their smaller magnitude of
      variation.

PMID- 8859267
TI  - Recurrent respiratory distress syndrome in successive preterm pregnancies.
AB  - BACKGROUND: Earlier studies suggesting an increased recurrence risk of
      respiratory distress syndrome (RDS) among the subsequent infants of women with a
      previously affected infant were based on low birth weight inclusion criteria that
      did not differentiate between preterm and growth-retarded infants. METHODS: We
      therefore carried out two cohort studies of women who delivered two singleton
      preterm (gestational age < 37 completed weeks) infants: 1978 to 1989 at the Royal
      Victoria Hospital (RVH) in Montreal and 1959 to 1966 in the United States
      Collaborative Perinatal Project (CPP). We compared the relative risk (RR) of the
      development of RDS in the second infant according to the RDS status of the first.
      The diagnosis of RDS was based on respiratory distress of more than 24 hours'
      duration and a reticulogranular pattern on a chest radiograph. RESULTS: The RVH
      study sample comprised 284 infants born to 142 women, and the CPP sample 642
      infants born to 321 mothers. In the RVH cohort the crude RR of RDS in the second
      sibling was 3.3 (95% confidence interval = 1.0 to 15.1) in women whose first
      preterm infant had RDS versus those whose first preterm infant did not have RDS.
      In the CPP cohort the corresponding RR was 2.5 (95% confidence interval = 0.8 to
      7.9). These elevated risks were not altered substantially when multiple logistic
      regression was used to control for potentially confounding factors known to
      influence the risk of RDS (gestational age, sex, route of delivery, antenatal
      corticosteroids, and respiratory depression of birth). CONCLUSIONS: We conclude
      that preterm infants born to women with a previous preterm infant affected by RDS
      are at an increased risk of RDS, which suggests an important genetic (or other
      familial) tendency in its origin.

PMID- 8859266
TI  - New evidence for neurobehavioral effects of in utero cocaine exposure.
AB  - Most studies of prenatal cocaine exposure have found gestational age or
      intrauterine growth deficits but few, if any, cognitive effects. In a large, well
      controlled study we detected cognitive deficits in relation to heavy cocaine
      exposure. These findings demonstrate that prenatal exposure to cocaine at
      sufficiently high doses early in pregnancy has the potential to produce cognitive
      changes in infants and that more focused, narrow-band tests may be necessary to
      detect these subtle neurobehavioral effects. A total of 464 inner-city, black
      infants whose mothers were recruited prenatally on the basis of pregnancy alcohol
      and cocaine use were tested at 6.5, 12, and 13 months of age. Standard analyses,
      based on presence or absence of cocaine use during pregnancy, confirmed effects
      on gestational age but failed to detect cognitive effects. A new approach to
      identifying heavy users found that heavy exposure early in pregnancy was related
      to faster responsiveness on an infant visual expectancy test but to poorer
      recognition memory and information processing, deficits consistent with prior
      human and animal findings. These persistent neurobehavioral effects of heavy
      prenatal cocaine exposure appear to be direct effects of exposure and independent
      of effects on gestational age.

PMID- 8859268
TI  - Unusual features of osteoarticular tuberculosis in children.
AB  - Three children with tuberculous arthritis, two of whom also had tuberculous
      otitis media, are described. Two of the children were atypical at presentation,
      with an acute onset of arthritis, an elevated erythrocyte sedimentation rate, and
      a predominance of polymorphonuclear cells in the joint fluid. Both had histories
      of recurrent otitis media with perforations. Recognition that Mycobacterium
      tuberculosis could be the cause of disease in all three cases was delayed.
      Placement of a tuberculin skin test ultimately led to the correct diagnosis.
      These cases Illustrate that tuberculous arthritis is not always insidious in
      onset and underscore the need to maintain a high index of suspicion for
      tuberculosis infection in high-risk patient populations. Our experiences suggest
      that Mantoux skin tests might be considered part of the "routine" diagnostic
      study of children with arthritis or recurrent otitis media, especially in
      communities with high tuberculosis case rates.

PMID- 8859269
TI  - Complications associated with severe invasive streptococcal syndrome.
AB  - Group A beta-hemolytic streptococcal sepsis may cause life-threatening disease.
      We describe a child with severe invasive streptococcal syndrome in whom severe
      respiratory failure and pulmonary pneumatoceles required extracorporeal life
      support. Physicians should be aware of the full spectrum of pathologic changes
      and life-threatening complications caused by group A beta-streptococcus.

PMID- 8859270
TI  - Methotrexate treatment of Wegener granulomatosis in children.
AB  - Wegener granulomatosis traditionally has been treated with glucocorticoids and
      cyclophosphamide. Both the disease and its treatments are associated with
      significant morbidity and mortality rates. There has been an effort to find
      effective but less toxic alternative treatments. We describe three children with
      Wegener granulomatosis who responded well to treatment with glucocorticoids and
      methotrexate, similar to a regimen used in adults.

PMID- 8859271
TI  - Metabolic rate and energy balance in very low birth weight infants during
      kangaroo holding by their mothers and fathers.
AB  - The aim of the study was to compare effects of maternal and paternal kangaroo
      care on oxygen consumption, carbon dioxide production, energy expenditure, skin
      and rectal temperatures, heart and respiratory rates, arterial saturation, and
      behavioral states. Eleven preterm infants with gestational age of 28 to 31 weeks,
      birth weight of 560 to 1390 gm, and postnatal age of 8 to 48 days were studied
      before, during, and after maternal and paternal kangaroo care. Skin temperature
      (lower leg) increased significantly during both maternal (36.2 +/- 0.9 degrees vs
      36.9 +/- 1.2 degrees C) and paternal (36.3 +/- 0.9 degrees vs 36.8 +/- 0.9
      degrees C) kangaroo care. The other parameter changed neither during maternal nor
      during paternal kangaroo care. We conclude that both maternal and paternal
      kangaroo care have no adverse effects on energy expenditure.

PMID- 8859272
TI  - A simplified six-item checklist for screening for fragile X syndrome in the
      pediatric population.
AB  - OBJECTIVE: In our general experience, about 2% of samples referred for fragile X
      testing showed positive results on Southern blot analysis. The aim of this
      project was to determine whether screening criteria could be developed to
      increase the proportion of positive test results without sacrificing sensitivity.
      STUDY DESIGN: We retrospectively analyzed nine clinical characteristics from
      patient records of 273 male and 62 female pediatric probands (average age, 5.7
      years) referred for fragile X testing. The characteristics included mental
      retardation, family history of mental retardation, large or prominent ears,
      elongated face, attention deficit hyperactivity disorder, autistic-like behavior,
      simian crease, macroorchidism, and hyperextensible joints. These were scored as 2
      if present, 1 If borderline present, and 0 if absent. RESULTS: Analysis of the
      nine characteristics identified three (simian crease, macroorchidism, and
      hyperextensible joints) with low frequency and statistical insignificance, which
      were therefore eliminated. With the use of the remaining six characteristics, If
      a score of 5 or more was used as the criterion for requesting fragle X testing,
      then close to 60% of those tests from our patient population could have been
      eliminated without missing any positive cases. The validity of our threshold
      score of 5 was subsequently confirmed among an additional six cases of fragile X
      syndrome. CONCLUSION: With our simplified six-item clinical checklist, 60% of
      testing could have been eliminated, thereby improving the cost-effectiveness of
      fragile X testing and increasing the proportion of cases with positive results by
      threefold.

PMID- 8859273
TI  - Neonatal presentation of Gordon syndrome.
AB  - Gordon syndrome, the association of hypertension with hyperkalemic acidosis, has
      been described in older children and adults. We report an affected family in
      which two of the members had exhibited the metabolic manifestations of the
      disease since infancy. Both patients responded well to thiazides. To our
      knowledge, these are the youngest patients with documented cases of Gordon
      syndrome.

PMID- 8859274
TI  - Retinopathy of prematurity: is suppression of neovascularization achievable?

PMID- 8859275
TI  - Pseudomonas aeruginosa infection in patients with cystic fibrosis.

PMID- 8859276
TI  - Herpes simplex: evolving concepts.
AB  - A large body of molecular biologic research has begun to clarify some basic
      aspects of viral latency and reactivation. The clinical definition of herpes
      simplex virus infection is expanding, with the recognition that the disease is
      largely asymptomatic and that most transmission occurs during periods of
      asymptomatic viral shedding. With this awareness, serologic diagnosis has become
      increasingly important. New treatment modalities are now available, and other
      promising treatments are in development.

PMID- 8859277
TI  - Localized involutional lipoatrophy: a clinicopathologic study of 16 patients.
AB  - BACKGROUND: Localized loss of adipose tissue without antecedent clinical or
      histologic inflammation is termed idiopathic lipoatrophy. OBJECTIVE: Our purpose
      was to study the clinical and pathologic features in 16 patients with clinically
      focal lipoatrophy and a distinct pathologic pattern of fat lobule involution.
      METHODS: A retrospective study of 16 patients was performed. RESULTS: The
      buttocks and proximal extremities were involved most frequently. Lesions were
      solitary in 10 patients and multiple in six. Nine patients had received
      intramuscular or intraarticular corticosteroid or antibiotic injections in the
      affected areas before the development of lipoatrophy. Histologic examination
      showed that individual fat cells were decreased in size and separated by hyaline
      material. Progressive reduction in the size and number of adipocytes resulted in
      diminutive fat lobules with prominent vessels resembling embryonic fat lobules.
      Some adipocyte masses were acidophilic. Scattered macrophages, confirmed by
      immunoperoxidase staining for CD68 (KP-1), were identified within the fat lobules
      and surrounding connective tissue. Yellow-gray granules were recognized within
      the cytoplasm of macrophages in nine cases. Macrophages becoming lipophages were
      observed by electron microscopy in one case. Other inflammatory cells were not
      prominent. CONCLUSION: This is a common pattern of postinjury response to fat
      tissue characterized by macrophage infiltration of the fat lobules in variable
      numbers. The term involutional lipoatrophy is justified by the resemblance of the
      distinctive pathologic changes to embryonic fat lobules.

PMID- 8859278
TI  - Neurocutaneous melanosis: clinical features of large congenital melanocytic nevi
      in patients with manifest central nervous system melanosis.
AB  - BACKGROUND: Patients with a large congenital melanocytic nevus (LCMN) may have
      associated leptomeningeal melanocytosis with or without central nervous system
      (CNS) melanomas. These patients are considered to have neurocutaneous melanosis,
      a disorder that, when symptomatic or otherwise manifest neurologically, carries a
      poor prognosis even in the absence of malignancy. OBJECTIVE: Our purpose was to
      identify typical clinical features in patients who have manifest CNS melanosis in
      association with LCMN. METHODS: The records of 117 patients with LCMN in the New
      York University Registry of LCMN and the reports of 172 cases of LCMN in the
      world literature were included for features that might signal a high risk for the
      development of manifest CNS involvement. RESULTS: Of the 289 patients with LCMN,
      33 had manifest CNS melanosis. In all 33 in whom symptomatic neurocutaneous
      melanosis was diagnosed, the LCMNs were present in a posterior axial location on
      the head, neck, back, and/or buttocks. "Satellite" nevi were known to be present
      in 31 of the 33 patients. CONCLUSION: Patients with LCMN in a posterior axial
      location, especially when associated with "satellite" melanocytic nevi, are at
      greater risk for the development of manifest neurocutaneous melanosis than
      patients with LCMN limited to the extremities or those who are lacking satellite
      nevi.

PMID- 8859279
TI  - A U.S. epidemiologic survey of superficial fungal diseases.
AB  - BACKGROUND: Large-scale studies performed outside the United States have
      demonstrated that most cases of onychomycosis and tinea pedis are caused by
      dermatophytes, primarily Trichophyton rubrum. However, other studies have
      suggested that yeasts and nondermatophytic molds may play a role, particularly in
      onychomycosis. OBJECTIVE: This study was undertaken to determine the epidemiology
      of superficial fungal infections in a U.S. population. METHODS: Fungal cultures
      were performed on patients with clinically suspected tinea cruris, tinea
      corporis, tinea capitis, tinea pedis, and onychomycosis. RESULTS: Dermatophytes
      were the most commonly isolated fungi in each type of superficial fungal disease
      studied. T. rubrum was the most commonly isolated dermatophyte species, although
      Trichophyton tonsurans was more common in tinea capitis and equally common in
      tinea corporis/tinea cruris. In tinea pedis and onychomycosis, dermatophytes
      appeared in approximately 95% and 82% of isolates, respectively. Candida albicans
      and nondermatophyte molds played only a minor role in onychomycosis; C. albicans
      was isolated in 7% of nail cultures and nondermatophytic molds were isolated in
      11%. CONCLUSION: These results are in general agreement with other major
      epidemiologic studies performed outside the United States. Dermatophyte fungi
      cause most superficial fungal infections.

PMID- 8859280
TI  - Utilization of outpatient care for psoriasis.
AB  - BACKGROUND: Little is known about the utilization of medical services for
      psoriasis. OBJECTIVE: Our purpose was to quantify the medical resources utilized
      in the United States for the treatment of psoriasis. METHODS: By utilizing data
      tapes from the National Center of Health Statistics we estimated the number of
      outpatient visits to physicians for psoriasis and the types of drugs prescribed.
      RESULTS: Visits to physicians in the United States made principally for psoriasis
      average 1.5 million per year. Topical steroids are most often prescribed. At less
      than 10% of visits are systemic therapies (methotrexate, psoralen, oral
      retinoids) prescribed. CONCLUSION: Although substantial medical resources are
      utilized in the treatment of psoriasis, the majority of affected persons make
      less than one visit per year to a physician for treatment.

PMID- 8859281
TI  - Synergistic topical photoprotection by a combination of the iron chelator 2
      furildioxime and sunscreen.
AB  - BACKGROUND: Iron is a factor in skin photodamage, apparently by way of its
      participation in oxygen radical production. Certain topical iron chelators are
      photoprotective. OBJECTIVE: Our purpose was to determine the level of topical
      photoprotection provided by the iron chelator 2-furildioxime (FDO) in combination
      with sunscreen in short- and long-term photoprotection models. METHODS: Guinea
      pigs were treated topically with FDO, sunscreen, and a combination of the two and
      were then exposed to varying doses of UV radiation to determine the sun
      protection factor (SPF). Hairless mice were treated topically with FDO,
      sunscreen, and a combination of the two and then subjected to long-term exposure
      to a suberythemal dose of UV radiation. The mice were evaluated for skin
      wrinkling and skin tumors. RESULTS: In guinea pigs, topical FDO combined with
      sunscreen provided more than additive protection; 5% FDO alone provides
      approximately SPF 4, whereas 5% FDO combined with an SPF 4 sunscreen product
      yielded an SPF of more than 30. In hairless mice exposed long term to UV
      radiation, 5% FDO and sunscreen delayed tumor onset by a mean of 8 and 12 weeks,
      respectively. The combination of FDO and sunscreen delayed tumor onset by a mean
      of 58 weeks. A similar more than additive level of protection was observed for
      skin wrinkling. CONCLUSION: Topical FDO combined with sunscreen is a potent
      photoprotection system against both short- and long-term UV radiation exposure.

PMID- 8859283
TI  - Value of urinary N-methylhistamine measurements in childhood mastocytosis.
AB  - BACKGROUND: Histamine is an indicator of mast cell activation. N-methylhistamine
      (NMH) is a metabolite of histamine that can be measured in urine. OBJECTIVE: Our
      purpose was to assess the usefulness of determining urinary NMH levels for the
      diagnosis and follow-up of patients with mastocytosis. METHODS: Urinary NMH
      levels were determined in 44 patients and were correlated with disease activity
      and extension. The control group consisted of 24 children without mastocytosis or
      any other skin disease. RESULTS: A significant negative correlation was found
      between NMH and age in patients with active mastocytosis and in the control
      group. Adjusted for age, NMH values were significantly higher in patients with
      active mastocytosis. There was a significant difference in NMH values between
      patients with diffuse cutaneous mastocytosis, patients with active urticaria
      pigmentosa, and patients with active mastocytomas. However, there was a
      substantial overlap of NMH values in the different subgroups. CONCLUSION: Urinary
      NMH values tend to decrease with age. Urinary NMH values correlated with the
      extent and the activity of the disease. High NMH values suggest more extensive
      involvement.

PMID- 8859282
TI  - Standard and high resolution magnetic resonance imaging of glomus tumors of toes
      and fingertips.
AB  - BACKGROUND: High-resolution magnetic resonance imaging (MRI) of subungual glomus
      tumors has been recently reported. OBJECTIVE: Our purpose was to compare high
      resolution MRI and standard MRI for the diagnosis of 44 glomus tumors of the toes
      and fingertips. METHODS: Glomus tumors (11 cases) were first examined by MRI with
      a commercial surface coil (set 1). Thirty-three other glomus tumors and one tumor
      from set 1 were then examined with a high-resolution module designed for skin
      imaging (set 2). RESULTS: All 44 glomus tumors were identified with MRI. The
      limits of the tumors were detected in 54% of set 1 and 100% of set 2. A capsule
      was present in most cases, but was incomplete or absent in eight cases. Subtypes
      of glomus tumors were more easily differentiated in set 2. CONCLUSION: Standard
      MRI was adequate to detect glomus tumors, but high-resolution MRI assessed tumor
      characteristics more accurately.

PMID- 8859284
TI  - A multirater validation study to assess the reliability of acne lesion counting.
AB  - BACKGROUND: Despite widespread use of acne lesion counting, little has been
      published on its reliability, particularly for multiple raters. OBJECTIVE: Our
      purpose was to assess reliability of acne lesion counting with the use of a five
      segment facial template. METHODS: After training, 12 raters each evaluated 12
      patients in randomized order, in the morning and again in the afternoon, and
      recorded counts for different types of lesions on a five-segment facial template.
      RESULTS: Individual raters could reproduce their total lesion counts (reliability
      estimates, 0.81 to 0.97). Variability between raters was high, and overall
      reliability estimated across raters was 0.61. For a subgroup of commonly trained
      raters, overall reliability was higher (0.80). CONCLUSION: The reliability of
      acne lesion counting is excellent when performed by the same trained rater over
      time. The high variability between raters appears to be reduced by standardized
      training. Because fewer lesions are counted with less variation, use of a
      template may have contributed to the high within-rater reliability.

PMID- 8859285
TI  - Acute lipodermatosclerosis is associated with venous insufficiency.
AB  - BACKGROUND: Acute lipodermatosclerosis is characterized by pain and tenderness in
      the medial aspect of the leg. It is thought to be the result of venous
      insufficiency and to be the acute counterpart of chronic lipodermatosclerosis, a
      hallmark of venous disease. However, there is no direct evidence linking acute
      lipodermatosclerosis to venous disease. OBJECTIVE: Our purpose was to determine
      whether acute lipodermatosclerosis is associated with venous insufficiency.
      METHODS: With air plethysmography, we determined the venous filling index, the
      ejection fraction, and the residual volume fraction in 15 sequential patients
      with acute lipodermatosclerosis. RESULTS: Ten of the 15 patients (67%) had at
      least one abnormal result, eight (53%) had two, and two (13%) had three. In four
      patients (27%), abnormalities of both reflux and ejection were noted. Duplex
      venous ultrasonography, in two of the patients with normal results from air
      plethysmography, showed incompetent perforators at sites of lipodermatosclerosis.
      CONCLUSION: Acute lipodermatosclerosis is associated with objective findings of
      venous insufficiency in a high percentage of patients. It is likely that this
      condition is the result of venous disease.

PMID- 8859287
TI  - Photopheresis therapy for cutaneous T-cell lymphoma.
AB  - BACKGROUND: Cutaneous T-cell lymphoma is a chronic peripheral lymphoma in which
      aggressive combined therapy elicits high response rates but does not improve
      survival. Photopheresis therapy has reportedly induced remissions and prolonged
      survival in patients with advanced disease. OBJECTIVE: We studied all patients
      who began photopheresis treatment between February 1988 and July 1994 to
      determine whether we could confirm the remission rates of previous studies, to
      evaluate variables that might predict a response, and to discover whether an
      accelerated delivery system would improve the remission rate or response time.
      METHODS: After an oral dose of methoxsalen was administered, a leukocyte-enhanced
      quantity of blood was exposed to UVA radiation for 1.5 hours and returned to the
      patient. With our accelerated system, 6 x 10(9) cells were irradiated in nine
      cycles. Treatments were given on 2 consecutive days once a month. RESULTS: Among
      34 patients whose results could be evaluated, the overall response rate (complete
      and partial remissions) was 50%; most patients had mild side effects. All
      responders except one had erythroderma. Responders had a decrease of 75% in mean
      skin scores, whereas nonresponders had an increase of 21%. CONCLUSION:
      Photopheresis appears to be effective for selected patients with erythrodermic
      cutaneous T-cell lymphoma, although we did not achieve as high a remission rate
      as previously reported by others.

PMID- 8859286
TI  - Botulinum A exotoxin for glabellar folds: a double-blind, placebo-controlled
      study with an electromyographic injection technique.
AB  - BACKGROUND: Botulinum A exotoxin (BTX) has been used successfully to treat a
      variety of hyperkinetic movement disorders. BTX is also capable of reducing
      hyperkinetic facial lines including prominent glabellar frown lines. OBJECTIVE:
      The purposes of this study were to (1) confirm the efficacy of BTX in a double
      blind, placebo-controlled investigation; (2) evaluate the use of an
      electromyogram attached to the injection needle to confirm intramuscular
      corrugator placement of the BTX; and (3) determine the optimum direction
      injection technique. METHODS: Length and depth of glabellar frown lines were
      measured before treatment and 4 and 12 weeks after injection of 10 units of BTX
      or saline solution. RESULTS: Patients treated with BTX had a highly significant
      reduction in depth and length of glabellar frown lines compared with control
      subjects. CONCLUSION: BTX appears to be effective and safe for reduction of
      glabellar frown lines.

PMID- 8859288
TI  - Nasal reconstruction with the cheek island pedicle flap.
AB  - BACKGROUND: Reconstruction of the lower third of the nose can be challenging.
      Maintaining the nasal subunit symmetry and providing good tissue match with
      regard to color, sebaceous quality, and thickness is essential. For extensive
      defects in this area, paramedian forehead flaps are often considered. OBJECTIVE:
      Our purpose was to develop the technique of preparing and executing the cheek
      island pedicle flap, as well as to define the limitations and "pitfalls" of the
      flap. METHODS: The cheek island pedicle flap is described. RESULTS: The cheek
      island pedicle flap can provide excellent cosmetic results in reconstructing
      defects of the lower third of the nose. The flap dynamics are predictable, and
      anticipated complications are described. CONCLUSION: The cheek island pedicle
      flap provides an excellent alternative to the paramedian forehead flap for
      reconstruction of extensive defects of the lower third of the nose.

PMID- 8859289
TI  - A clinicopathologic approach to granulomatous dermatoses.
AB  - Reaching a diagnosis or formulating a differential diagnosis in dermatopathology
      involves combining information from clinical and pathological sources.
      Traditionally, this process is presented as a chronologic progression from the
      patient's complaint, through the evaluation of findings, terminating in the
      microscopic examination of the biopsy specimen. However, dermatopathologists
      often find the sequence reversed. They must first form an impression of the
      diagnosis from the slide and then supplement it with clinical information. The
      purpose of this article is to present the spectrum of granulomatous dermatoses
      from a pathologic perspective. The dermatoses are categorized into five groups on
      the basis of histologic patterns.

PMID- 8859290
TI  - Genital herpes: an integrated approach to management.
AB  - This review of epidemiologic, clinical, and psychosocial/psychobehavioral data
      related to genital herpes simplex virus infection details the increasing
      incidence of herpes simplex virus infection in the United States and summarizes
      the data regarding the safety and efficacy of chronic and acute antiviral therapy
      with acyclovir. It additionally establishes the validity of psychosocial
      intervention as an adjunct to pharmacologic therapy for patients with recurrent
      genital herpes.

PMID- 8859291
TI  - An evaluation of the accuracy of residency applicants' curricula vitae: are the
      claims of publications erroneous?
AB  - Competition for residency positions in dermatology is intense. Training programs
      in other disciplines have described significant misrepresentation among their
      applicants in claims of research and publication. An evaluation was made of the
      curricula vitae for the 138 applicants with completed applications for our 1994
      residency match. Cited articles were placed in four categories: "published," "in
      print/in press," "submitted for publication," and "in preparation/in progress."
      We found significantly less misrepresentation than has been described in other
      specialty training programs. Simplification of the way in which applicants verify
      their bibliography may reduce erroneous citations and remove implications of
      willful misrepresentation of academic achievements.

PMID- 8859292
TI  - Guidelines of care for scleroderma and sclerodermoid disorders. American Academy
      of Dermatology.

PMID- 8859293
TI  - Guidelines of care for the use of topical glucocorticosteroids. American Academy
      of Dermatology.

PMID- 8859294
TI  - Guidelines of care for vitiligo. American Academy of Dermatology.

PMID- 8859295
TI  - Clinical pearl: discoid lupus erythematosus--treatment with occlusive
      compression.

PMID- 8859296
TI  - Sweet's syndrome induced by granulocyte colony-stimulating factor in a woman with
      congenital neutropenia.

PMID- 8859297
TI  - Erythema of the proximal nailfold in HIV-infected patients.

PMID- 8859298
TI  - Circle hairs are not rolled hairs.

PMID- 8859299
TI  - Is mycosis fungoides exacerbated by fluoxetine?

PMID- 8859300
TI  - Treatment of tinea capitis with itraconazole.

PMID- 8859301
TI  - Fixed food eruption.

PMID- 8859302
TI  - Sjogren's syndrome associated with thymoma.

PMID- 8859303
TI  - Intracranial osteolytic meningioma affecting the scalp.

PMID- 8859304
TI  - Retrospective review of the use of azathioprine in severe atopic dermatitis.

PMID- 8859306
TI  - Two patients with confluent and reticulated papillomatosis: response to oral
      isotretinoin and 10% lactic acid lotion.

PMID- 8859305
TI  - Propolis allergy in an HIV-positive patient.

PMID- 8859307
TI  - Nonpigmented fixed drug eruption from pseudoephedrine.

PMID- 8859308
TI  - Every day is melanoma Monday.

PMID- 8859309
TI  - Dermatoheliosis?

PMID- 8859310
TI  - More on cutaneous reactions to recombinant cytokine therapy.

PMID- 8859311
TI  - Cold panniculitis in a neonate.

PMID- 8859312
TI  - Dermabrasion and epithelial sheet grafting.

PMID- 8859313
TI  - Molecular biology by numbers ..... three.

PMID- 8859314
TI  - Biology: my old girlfriend.

PMID- 8859315
TI  - Loose ends.

PMID- 8859316
TI  - Decisions, decisions.

PMID- 8859318
TI  - Unit precedent.

PMID- 8859317
TI  - The good fairy godmother of science.

PMID- 8859319
TI  - Biology on the web.

PMID- 8859320
TI  - Suzanne Cory: from a table to the top.

PMID- 8859321
TI  - Net sequence gazing.

PMID- 8859322
TI  - And now it's time for tea.

PMID- 8859323
TI  - Molecular biology by numbers ellipsis four.

PMID- 8859325
TI  - To meet, to gossip.

PMID- 8859324
TI  - The good fairy godmother of evolutionary genetics.

PMID- 8859326
TI  - Hero worship.

PMID- 8859327
TI  - Out of Africa.

PMID- 8859329
TI  - Brave new media.

PMID- 8859328
TI  - Degradation of ancient DNA.

PMID- 8859330
TI  - Publishing on the net.

PMID- 8859331
TI  - The only fault's with time.

PMID- 8859332
TI  - Biology applied to chemistry.

PMID- 8859333
TI  - Molecular design - the easy way.

PMID- 8859396
TI  - Perfectionism in weight-concerned and -unconcerned women: an experimental
      approach.
AB  - OBJECTIVE: The primary purpose of the study was to explore, experimentally, the
      common clinical observation that anorexics are highly perfectionistic. METHOD:
      Extremely weight-concerned and control college student subjects (as defined by
      scores on the Eating Attitudes Test [EAT]) were assigned high or low goals or
      they selected their own goals in a performance situation. After a series of 10
      trials on which personal performance goals were measured, subjects in the high
      and low goal groups received false feedback indicating success or failure, and
      mood was measured. RESULTS: High (vs. low) EAT subjects were more likely to
      persist in accepting an unrealistically high imposed goal, set lower personal
      goals in the absence of external standards, and were more strongly affected by
      the feedback. DISCUSSION: Many characteristics of anorexics (including pursuit of
      thinness) can be accounted for in terms of their strong need for social approval
      and conformity to external standards.

PMID- 8859397
TI  - The use of the eating disorder examination with children: a pilot study.
AB  - OBJECTIVE: This article describes the use of a slightly modified version of the
      Eating Disorders Examination (EDE) in children. METHODS: Sixteen children aged
      between 7 and 14 years attending an eating disorders clinic over a 5-month period
      were recruited to the study. The two main modifications to the EDE were (A) the
      inclusion of a sort task to assess overvalued ideas about weight and shape and
      (B) the reformulation of certain items to assess intent rather than actual
      behavior. The existing EDE scoring system was used, resulting in item, subscale,
      and global scores. RESULTS: Of the 16 children (10 F 6 M), 11 had a diagnosis of
      anorexia nervosa, and 5 of eating disorder not otherwise specified (EDNOS). There
      were interesting differences in responses on items assessing core overvalued
      ideas, with weight and/or shape concerns emerging as of great importance in terms
      of self-evaluation in the majority of children with anorexia nervosa. DISCUSSION:
      Results suggest that this may be a useful assessment tool in children, with some
      children obtaining global and subscale scores consistent with adult norms for
      females with eating disorders. Problems of the administration of the EDE to this
      patient group are discussed and details of the modifications used are outlined.

PMID- 8859398
TI  - Discriminant function analysis of depressive symptoms in binge eating disorder,
      bulimia nervosa, and major depression.
AB  - OBJECTIVES: To examine the frequency and distribution of depressive symptoms
      among subjects with binge eating disorder (BED), bulimia nervosa (BN), and major
      depression. METHODS: This study examined depressive symptoms from the Hamilton
      Depression Scale in 122 BED, 142 BN, and 200 major depression subjects using
      discriminant function analysis. RESULTS: All three groups differed significantly
      on the Hamilton Depression Scale totals with major depressive disorder (MDD)
      subjects having the highest and BED subjects the lowest totals. Eighteen items
      differentiated MDD from the eating disorder groups. Three items-gastrointestinal
      (GI) somatic symptoms, paranoid symptoms, and obsessional symptoms-distinguished
      BED and BN. In each case these symptoms were more common in BN subjects.
      DISCUSSION: This study attempted to differentiate BN from BED on a basis other
      than eating behavior. The results provide limited support for the hypothesis that
      BN and BED can be distinguished on the basis of depressive symptoms.

PMID- 8859399
TI  - Task dependence in color-naming latency among dieters.
AB  - OBJECTIVE: This study was concerned with the robustness of responses to food- and
      to body-related words within a modified Stroop procedure. METHOD: A within
      subjects repeated measures design with 30 female dieters was used in order to
      examine task dependence in slowed color naming, with comparisons involving
      different dependent measures and the subjects' responses to the same stimuli
      using a simple computerized task. RESULTS: The color naming of food words was
      retarded when compared to neutral words, and more food words than neutral words
      were seen to appear first in the simple computerized decision task using the same
      lists of words. In contrast, the time taken to color name body and neutral words
      did not differ. DISCUSSION: Taken together, these results emphasize that these
      effects are not confined to patients with an eating disorder, and may simply
      reflect current community concern with healthy eating (and dieting). It is
      premature to advocate the Stroop procedure as an index of psychopathology, since
      it requires some evidence for the specificity of responses among patients with an
      eating disorder, and more importantly, a consensus about what might be involved
      in producing such effects.

PMID- 8859400
TI  - Burned out binge eaters: a preliminary investigation.
AB  - OBJECTIVE: The purpose of this study was to compare individuals who meet all the
      diagnostic criteria for binge eating disorder (BED), except loss of control, to
      individuals with BED and eating disorder not otherwise specified (EDNOS) on
      weight history variables. METHOD: Subjects were solicited among new participants
      in weight loss programs, with 35 meeting BED criteria, 47 meeting criteria for
      EDNOS, and 6 meeting criteria for BED without loss of control. RESULTS: Groups
      were not found to differ on age of onset of overweight or dieting, age of first
      binge, rate of largest weight loss, or number of times of losing 10 + lb. Groups
      did differ on highest weight ever and current body mass index (BMI). Subjects
      with BED without loss of control had a significantly higher highest weight and
      current BMI than both BED and EDNOS subjects. DISCUSSION: The results suggest
      that individuals reporting all the symptoms of BED except loss of control may be
      "former" BEDs who have "given up" on efforts to control their binge eating.

PMID- 8859401
TI  - Immunologic cytofluorometric studies in adolescents with anorexia nervosa.
AB  - OBJECTIVE: To assess lymphocyte stimulation and lymphocyte phenotype evaluation
      in adolescent patients with anorexia nervosa (AN). METHOD: In vitro lymphocyte
      stimulation and flow cytometric phenotype studies were done on 26 hospitalized
      patients with AN receiving nutritional rehabilitation. The laboratory assessment
      consisted of lymphocyte subset analysis and in vitro lymphoproliferative
      responses to mitogens and antigens. RESULTS: Flow cytometric phenotype analysis
      showed that only a minority of the patients had abnormal phenotype and immune
      responses, moreover their immune systems were not significantly impaired.
      DISCUSSION: The cytofluorometric study of immune function does not show
      significant alterations in adolescents hospitalized for anorexia nervosa.

PMID- 8859403
TI  - Small caliber vascular grafts. Part I: state of the art.
AB  - Vascular grafts, devices designed to augment inefficiently functioning vascular
      systems, represent a significant part of implantable medical devices, with major
      participation in over a million vascular surgeries performed worldwide. By
      definition accepted in the art, a small caliber graft is a conduit with internal
      diameter (ID) of 6 mm or less; large caliber grafts start at ID of 7 mm. While
      the autologous grafts utilizing saphenous veins (SVG) and internal iliac, or
      mammary arteries are used exclusively in cardiac artery bypass grafts (CABG)
      procedures and preferentially in many peripheral indications, and while the use
      of grafts with biological origin did not proliferate, polymer-based artificial
      grafts of controlled patterns and porosity are prostheses of choice for the large
      caliber. The polyester (PET) yarn is knitted or woven into various porous
      patterns. The PTFE tubes are expanded into porous conduits (ePTFE). Although
      these technologies are used to produce the grafts with ID larger than 6 mm, the
      dominant principles are being applied to the development of small caliber graft.
      Polyurethanes are also evaluated for small caliber application. The grafts
      (regardless of the ID) produced by the above technologies are porous. This
      porosity, considered to be critical for proper healing and overall graft patency,
      causes the blood to leak through the graft wall or at anastomosis through the
      suture holes. Both the wall leakage and suture hole bleeding remain rather
      serious drawbacks. Currently, collagen, gelatin, albumin and their derivatives
      are used as sealants. Various modes of application and degrees of crosslinking
      are utilized to control in vivo degradation and graft healing. Other hydrogels,
      both natural and synthetic, could play significant roles as sealants and
      modifiers of the graft performance. Enhancement of graft patency via improvement
      of initial hemocompatibility could be achieved by application of bioactive
      coatings. Heparinized systems seem to dominate in this field, but many new
      concepts are being investigated. Intraluminal endothelialization via mediating
      biologicals could open significant potential for synthetic small caliber grafts.
      Furthermore, porous biodegradable tubes could be used as temporary scaffold to
      attract and promote cell propagation and ingrowth, the true angiogenesis. Part I
      of this series discusses the "S.O.T.A" of the small caliber graft. The following
      parts will discuss concepts needed for development of truly patent small caliber
      grafts and will report on our progress in the development of biodurable and
      pulsatile grafts for vascular access, peripheral, and potentially for CABG
      indications.

PMID- 8859404
TI  - Surface modification of titanium based biomaterials by ion beam.
AB  - Ion beam enhanced deposition (IBED) was adopted to synthesize biocompatible
      titanium oxide film. Structure characteristics of titanium oxide film were
      investigated by RBS, AES, and XRD. The blood compatibility of the titanium oxide
      film was studied by measurements of blood clotting time and platelet adhesion.
      The results show that the anticoagulation property of titanium oxide film is
      improved significantly. The mechanism of anticoagulation of the titanium oxide
      film was discussed.

PMID- 8859406
TI  - Studies on microleakage associated with visible light cured dental composites.
AB  - The objective of this investigation was twofold: 1) to determine the extent of
      microleakage associated with two visible light cured dental composites, one of
      which is an indigenously developed light cure composite (chitra light cure
      system) compared with a commercially available control material (Prisma APH light
      cure system), and 2) to study the effect of using bonding agents upon the above
      phenomena. The bonding agents used along with the above composites during
      restoration were chitra bonding agent system containing chitra primer/chitra
      resin and a control (Probond) which was purchased commercially. A comparison of
      microleakage in freshly restored human premolar teeth by silver nitrate staining
      technique was made during the above study. Cavities were restored with both
      composites with and without bonding agents, stored in 50 percent silver nitrate,
      and sections were cut after developing. The microtomed sections were observed
      under the optical light microscope and scanning electron microscope. Results
      indicate that bonding agents are mandatory for effective bonding at the
      tooth/resin interface and subsequent reduction in marginal leakage. Chitra
      bonding agent showed excellent adhesive bonding characteristics at the
      dentine/composite interface with minimal marginal leakage compared to the control
      bonding system. The chitra light cure composite material also showed lower
      shrinkage characteristics compared to Prisma APH composite.

PMID- 8859405
TI  - In vitro release of new quinolones from biodegradable systems: a comparative
      study.
AB  - A new biodegradable delivery system based on low molecular weight poly(lactic
      acid) has been formulated, with potential application in the sustained antibiotic
      release against bone infection. The in vitro release of two new quinolones
      (ofloxacin and ciprofloxacin) from the biodegradable matrix showed that the
      delivery of ofloxacin from the matrix lasted fifty-six days, whereas that of
      ciprofloxacin lasted fifty-one days. In both cases, release is controlled by the
      drug diffusion and the matrix degradation, the latter being the most critical
      factor. The obtained concentration levels are well above the Minimum Inhibitory
      Concentration (MIC) against the major causative bacteria of osteomyelitis. This
      fact in combination with the good reproducibility of measurements indicated that
      the system studied could be of value for the preparation of implantable
      controlled release systems for treatment of diseases in the bone system.

PMID- 8859487
TI  - Retrospective survey of a link between cat and dog antigens and allergic
      conjuctivitis.
AB  - This retrospective 3-year study was designed to determine (a) which antigen
      positive patients were found in greater numbers, (b) whether the patients who
      were positive for cat or dog antigen-specific IgE were also positive for other
      antigens, and (c) whether the number of patients with allergic conjunctivitis
      increased during a particular time of the year. A total of 762 patients were
      diagnosed with allergic conjunctivitis including 107 cat-positive and/or dog
      positive patients. Cat-positive patients were more prevalent than dog-positive
      patients, (p < 0.001). All but 2 patients were positive for other antigens,
      indicating a strong link between the animal antigens and other antigens. Cat and
      dog allergy increased in spring and early summer.

PMID- 8859488
TI  - Absorption of topically administered ciprofloxacin, ofloxacin and gentamicin in
      the inflamed rabbit eye.
AB  - The authors evaluated the ocular absorption of ciprofloxacin, ofloxacin and
      gentamicin as a reference drug in a novel model of ocular inflammation. The
      ocular absorption of ciprofloxacin and ofloxacin was shown to be increased two-
      to threefold in the inflamed eye. The absorption of gentamicin was undetectable
      in the normal eye and very poor in the inflamed eye.

PMID- 8859489
TI  - Unilateral acute posterior multifocal placoid pigment epitheliopathy.
AB  - A 24-year-old woman complained of paracentral scotomas in her left eye. Her
      visual acuity was good bilaterally. Multifocal, creamy, yellow-white lesions were
      seen at the level of the pigment epithelium and choroid in the left fundus.
      Fluorescein angiography showed blockage at the early phase and hyperfluorescence
      at the late phase in the left eye. The right fundus remained normal during the
      follow-up period of 1 year. We believe that unilateral acute posterior multifocal
      placoid pigment epitheliopathy, as found in our patient, may be uncommon.

PMID- 8859490
TI  - Congenital hypertrophy of the retinal pigment epithelium in the macula.
AB  - We describe a patient with congenital hypertrophy of the retinal pigment
      epithelium (CHRPE) in the macular area of the right eye. The patient had no
      ocular complaints. Only relative central scotoma and a tritan opic defect were
      demonstrated in the affected eye, suggesting that CHRPE in the macula had hardly
      affected the function of the cones in the diseased area.

PMID- 8859493
TI  - A lifetime of events: age and gender variations in the life story.
AB  - This study adopted a structural perspective in the examination of life events in
      the context of an individual's life story. Ten men and ten women at each of three
      age groups (young, middle-aged, and older adulthood) identified, on a time line,
      personally significant life events from their past and anticipated future.
      Results indicated that women identified a greater number of life events and
      reported a younger age corresponding to their first event than did men; this was
      especially true for older women. Older participants, in general, identified fewer
      future events than did younger participants and reported an older age for their
      last event; the corresponding range of time covered from the first to the last
      event was also longer. Event type also varied by age and gender. Recency played a
      central role in the allocation of life events, although late adolescence and
      early adulthood were especially dense event periods for all groups. Discussion
      focuses on the roles of gender, age, and the life course in the ways in which
      events are configured in the life story.

PMID- 8859494
TI  - Understanding the influence of gender role identity on the assumption of family
      caregiving roles by men.
AB  - Previous explanations of limited participation by males as family caregivers
      assume that socialization to dominant gender stereotypes is a universal barrier
      among men. Overlooked are 1) variations in the degree of internalization of
      gender typed attitudes that enable intense participation in a wide variety of
      personal care tasks and the assumption of the chief caregiver role among some
      men, and 2) social psychological processes used to resolve cognitive dissonance
      among men considering caregiver activities and/or role enactment. The present
      examination of these processes is responsive to calls for enhancing our
      understanding of the personal meaning that caregiving has for men. The
      introduction of Risman's view that current experience influences socialized
      predispositions, allows the delineation of conditions under which husbands, sons,
      and other male relatives who have internalized stereotypical self images of
      masculinity can also assume caregiver roles in the family. Drawing on interview
      data from a purposive sample of thirty-two men who were chief caregivers for
      elderly relatives, case study material is presented to illustrate several
      pathways by which male respondents gained access to family caregiving roles.

PMID- 8859495
TI  - Participation in leisure activities by older adults after a stressful life event:
      the loss of a spouse.
AB  - This study aimed to establish if frequent participation in leisure activities
      helped widows and widowers adapt to widowhood, and to maintain lower stress
      levels. A small sample of sixty recently bereaved widows (n = 43) and widowers (n
      = 17) who were living in an Australian city were selected for the study. Their
      ages ranged from fifty to eight-four years with a mean age of sixty-four years.
      Each widow or widower was interviewed and provided responses to three scales
      measuring participation in leisure activities, adaptation to widowhood, and
      stress. Quantitative and qualitative research techniques were used to interpret
      the data. The leisure activities most frequently participated in by widows and
      widowers were found to be home based activities, involving social activities with
      family and friends. Greater participation in leisure activities was found to be
      negatively correlated with stress scores, suggesting an association between
      leisure participation and stress reduction for recently bereaved widows and
      widowers. However, the study failed to find any association between participation
      in leisure activities and adaptation after the death of a spouse. In addition, no
      significant differences were found in the age, gender, income, and type of
      employment of widows and widowers, although perceived health status was found to
      be a significant factor in helping to determine future participation in leisure
      activities.

PMID- 8859496
TI  - Self-reported sleep disturbance among African-American elderly: the effects of
      depression, health status, exercise, and social support.
AB  - The prevalence and correlates of self-reported difficulties in initiating and
      maintaining sleep were investigated for a sample of 998 Black elderly. In terms
      of prevalence, only 68.3 percent of this sample had no trouble falling asleep.
      Over 14.5 percent of men and 23.6 percent of women participants in this study
      reported sleep latencies exceeding thirty minutes. Almost 13 percent reported
      getting less than four hours of sleep at night. Moreover, 14.5 percent of
      participants wake up at least three times during a typical night's sleep other
      than to use the bathroom and 45.3 percent said when they wake up during the
      night, they remain awake at least thirty minutes before falling back to sleep.
      Compared to men, women reported longer sleep latency, waking up more frequently
      at night, and were more likely to visit a health practitioner for sleeping
      problems. Multivariate analysis indicates that self-reported sleep problems were
      significantly greater among Black elderly who were women, with a higher level of
      depression/anxiety, those with a higher number of chronic illnesses, those who
      did not exercise, and those who reported lower levels of emotional social
      support.

PMID- 8859583
TI  - Enhancement efficacy of magnetic starch microshperes (MSM) in conventional spin
      echo and turbo spin-echo sequences at 0.5 T and 1.5 T.
AB  - The efficacy of the superparamagnetic contrast agent magnetic starch microspheres
      (MSM) was evaluated in vitro by NMR relaxometry and in vivo by MR imaging using
      T2-weighted spin-echo (SE) and turbo spin-echo (TSE) sequences at 0.5 T and 1.5 T
      in 60 normal rats who received MSM in doses of 10-50 mu mol/kg. MR imaging was
      performed using T2-weighted SE and TSE sequences. The relaxation rates 1/T1 and
      1/T2 for liver and spleen increased linearly with MSM concentrations up to 30 mu
      mol/kg body weight, and approached almost constant levels for higher doses. The
      slopes in the linear part of the 1/T2 diagram were 0.62 Hz +/- 0.03 for the liver
      and 0.51 Hz +/- 0.06 x kg/mu mol for the spleen. On all T2-weighted sequences at
      0.5 T and 1.5 T, liver signal-to-noise ratio (SNR) decreased by a factor of 2-3
      already at the lowest dose of 10 mu mol/kg. SNR values of TSE sequences exceeded
      values for SE sequences by 50-80%. The SNR decrease was not significantly
      different between SE and TSE sequences. Our results show that MSM is well suited
      as a T2 contrast agent at both magnetic field strengths when using conventional
      SE and fast TSE sequences.

PMID- 8859584
TI  - On the stationary states in gradient echo imaging.
AB  - A formalism is presented that concisely describes the magnetization of a sample
      subjected to a periodic series of RF pulses. In this formalism, the steady state
      of the magnetization is shown to be a sum of magnetic substates, each with unique
      contrast characteristics. When more than one substate contributes to a given
      image, the substates interfere with each other, producing ghosts and other
      artifacts. Properly designed gradient protocols can image single substates,
      producing ghost-free images. The contrast of the image depends largely on the
      choice of the imaged substate. Analytic solutions for unspoiled, RF spoiled, and
      gradient spoiled magnetizations are presented.

PMID- 8859585
TI  - Line scan imaging of brain metabolites with CPMG sequences at 1.5 tesla.
AB  - A line scan Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic imaging sequence has
      been implemented on a standard 1.5 T clinical scanner to map metabolite signals
      at multiple echo times from voxels along selected tissue columns through the
      brain. The CPMG multiecho spectroscopic image data sets are used to estimate
      brain metabolite T2 decay parameters in a group of healthy volunteers and in one
      tumor patient. Inherent trade-offs between T2 decay, spectral resolution, and
      echo spacing prove to be important limiting factors. In particular, separate
      quantitation of choline and creatine resonances at 1.5 T was not achieved in the
      present implementation. However, the ability to collect data sets suitable for T2
      decay analyses of combined choline and creatine resonances and N-acetyl aspartate
      resonances in under 10 minutes may prove of clinical utility in the study of
      brain pathology.

PMID- 8859586
TI  - Hepatocellular carcinoma exhibiting a concentric structure of different
      histologic grades: evaluation by chondroitin sulfate iron colloid-enhanced MR
      imaging.
AB  - A patient with hepatocellular carcinoma exhibiting a concentric structure of
      different histologic grades was examined with chondroitin sulfate iron colloid
      (CSIC)-enhanced MR imaging. After CSIC injection, the advanced component was
      enhanced in comparison with the surrounding liver, and the well-differentiated
      component was not enhanced. CSIC-enhanced MR imaging was helpful in evaluating
      histologic grade on the basis of reticuloendothelial function.

PMID- 8859587
TI  - Effects of intravoxel velocity distributions on the complex difference method of
      phase-contrast MR angiography.
AB  - The complex difference method of phase-contrast MR angiography is affected not
      only by the degree of velocity encoding applied during the scan but also by the
      variance of the intravoxel velocity distribution. The reconstructed intensities
      of voxels with the same average flow rate but different variances of the velocity
      distribution can differ significantly. Mathematical analysis and scanner phantom
      experiments confirm this conclusion.

PMID- 8859588
TI  - Additional information pertaining to the MR-compatibility of biopsy needles and
      devices.

PMID- 8859600
TI  - Statistics and clinical oncology.

PMID- 8859601
TI  - Large vessel effects of cytotoxic chemotherapy.

PMID- 8859602
TI  - Guidelines for radioactive iodine treatment of hyperthyroidism.

PMID- 8859603
TI  - Radiotherapy for pituitary adenomas: an endocrinologist's perspective.

PMID- 8859604
TI  - Follow-up of women treated for breast cancer.

PMID- 8859605
TI  - A linear quadratic analysis of gynaecological brachytherapy.
AB  - Four hundred and fourteen patients were treated by radical radiotherapy alone for
      cervical carcinoma at the Western Infirmary and the Royal Beatson Memorial
      Hospital between April 1982 and December 1987. All patients received external
      beam radiotherapy in addition to brachytherapy, using either manually inserted
      caesium (n = 107) or the Selectron afterloading machine (n = 307). Three mean
      Selectron dose rates were used: 0.91 Gy/h, 1.195 Gy/h and 1.74 Gy/h. During this
      period of time, the cumulative radiation effect formula was used to calculate an
      overall brachytherapy dose reduction to compensate for the increase in point 'A'
      dose rate. We have compared the local control rates and the incidence of late
      effects seen in these patients with theoretical parameters calculated using the
      linear quadratic (LQ) model. This model predicts a small rise in late effects as
      the dose rate increases, which is also seen in clinical practice; it also
      predicts a reduction in local control, partially offset by the addition of
      external beam radiotherapy, which would be most marked for early stage disease.
      There was a small fall in local control associated with Selectron treatment, but
      of a smaller size than predicted by the LQ model.

PMID- 8859606
TI  - The absence of an adverse effect of prolongation of radiation treatment of
      primary rectal adenocarcinoma.
AB  - Many reports have shown a deleterious effect from the prolongation of radiation
      treatment duration on local control of squamous cell carcinomas in a variety of
      sites. To study whether a similar effect was found in adenocarcinoma of the
      rectum, a retrospective review was performed of 353 patients treated by external
      beam radiation therapy for primary adenocarcinoma of the rectum. At 4 years, the
      local control rate for mobile tumours was 25 percent; for fixed tumours it was 7
      percent. By multiple Cox regression analysis, the only factor statistically
      significant for local control was tumour fixation (P=0.02). Neither treatment
      length (P=0.44), nor the presence of an interruption in treatment (P=0.41) was
      significant. The possible explanations for these observations are discussed.

PMID- 8859607
TI  - Small cell carcinoma of the cervix.
AB  - Small cell carcinoma of the cervix represents an uncommon variant of cervical
      cancer with a particularly poor prognosis. Traditionally, the diagnosis was
      established from routine histopathological sections, but there has been a trend
      to refer to this tumour as neuroendocrine carcinoma, with a requirement to
      demonstrate cytoplasmic granules. Five patients are described, who share the
      clinical features of young age of onset, early metastasis in the presence of
      apparently low stage disease, early failure of appropriate local treatment, and
      extreme chemosensitivity (features that are quite distinct from those seen in
      squamous cell cancer of the cervix). Light microscopy suggested a diagnosis of
      small cell cancer in all five tumours, but not all showed evidence of
      neuroendocrine differentiation. It is proposed that the present criteria for the
      diagnosis of cervical small cell carcinoma are too strict. The diagnosis should
      rely on the light microscopy of haemotoxylin and eosin sections and the
      distinctive clinical behaviour. The absence of neuroendocrine differentiation
      should not exclude the diagnosis, it does not appear to influence the clinical
      behaviour. The appropriate management of small cell carcinoma of the cervix is
      systemic, with chemotherapy as the first line of treatment. Surgery and
      radiotherapy may improve control of local disease but are unlikely significantly
      to influence the overall prognosis.

PMID- 8859608
TI  - Management of mucositis in oral irradiation.
AB  - Mucositis significantly affects quality of life and tolerance of treatment in
      oral irradiation. Effective management of this complication is therefore very
      important. However, there is a scarcity of up-to-date oral care protocols, with
      most centres using ritualized regimens. The literature on oral rinses in
      radiation mucositis is at best inconclusive and at worst confusing. In this
      study, patients undergoing radical radiotherapy treatment (55-60 Gy in 4 weeks)
      to more than 50% of the oral cavity and oropharynx were randomized to a research
      based oral care protocol with either saline 0.9% or hydrogen peroxide 3.5 volumes
      (HP) as rinses. The results of this study show that, on average, the group
      receiving saline rinses appeared to do better on some outcomes than the group
      receiving HP. This suggests that frequent mechanical cleansing of the mouth may
      be more important than the antiseptic properties of a mouthwash. Antiseptic
      mouthwashes may be contra-indicated in radiation mucositis. In order to determine
      best practice in mucositis management, multi-centre, multidisciplinary trials
      should be conducted.

PMID- 8859609
TI  - Oral indomethacin and ranitidine in advanced melanoma: a phase II study.
AB  - As a result of preclinical data demonstrating the antitumour and antimetastatic
      efficiency of indomethacin in murine models, and the clinical observation of
      occasional tumour regression in patients with advanced melanoma treated with
      indomethacin together with ranitidine, a Phase II study was performed of
      prolonged administration of these two oral agents in combination. Seventeen
      patients were entered into the study and commenced on indomethacin 50 mg three
      times daily; the dose was escalated to a maximum of 75 mg three times daily in
      patients who tolerated the starting dose. Ranitidine was administered
      concurrently at a dose of 150 mg twice daily. One patient with uveal melanoma
      metastatic to the liver achieved a partial response, with slow shrinkage of a
      biopsy-proved liver metastasis (objective response rate 6 percent; 95 percent CI0
      29). Another patient demonstrated a minor response in pelvic lymph nodes. The
      combination of indomethacin and ranitidine has negligible activity in advanced
      malignant melanoma; a response may require months to be achieved.

PMID- 8859610
TI  - Acute mesenteric ischaemia associated with 5-FU, cisplatin and vincristine
      chemotherapy.
AB  - We report a patient with acute superior mesenteric ischaemia following the use of
      cisplatin, 5-fluorouracil and vincristine combination chemotherapy. From a review
      of the literature, the possible mechanisms of acute vascular toxicity following
      chemotherapy are discussed.

PMID- 8859611
TI  - Pulmonary metastases, an occult prostatic adenocarcinoma and delayed
      administration of antiandrogens.
AB  - The presentation of prostatic carcinoma with pulmonary metastases is unusual. The
      patient reported here presented with nodular lung metastases from an unknown
      primary site and 3.5 years later became symptomatic with a prostatic carcinoma.
      Subsequent hormonal therapy led to radiological regression of the pulmonary
      metastases. This case report demonstrates the progression of asymptomatic
      prostatic lung metastases with time and their response to delayed hormonal
      therapy, which is discussed.

PMID- 8859612
TI  - Extramedullary haematopoiesis in thalassaemia: results of radiotherapy: a report
      of three patients.
AB  - Extramedullary haematopoiesis is sometimes encountered in severe anaemia. Rarely,
      it may cause neurological symptoms, leading to spinal cord or cauda equina
      compression. Three patients with thalassaemia intermedia, who developed
      neurological complications, are described. The diagnoses were based on the
      clinical findings, computed tomography and magnetic resonance imaging. Small
      doses of radiotherapy (10-20 Gy in 5-10 fractions) relieved symptoms in all of
      these patients. Our experience supports the role of radiation therapy as a
      treatment for this complication.

PMID- 8859613
TI  - Sacral chordoma, gas gangrene and bilateral renal cell carcinomas.
AB  - The case history is reported of a 59-year-old man with a locally symptomatic
      sacral chordoma. During treatment with radical radiotherapy, he developed gas
      gangrene, which proved rapidly fatal. At post-mortem examination there was
      evidence of local invasion of the rectum by the tumour and extensive gangrenous
      myonecrosis (gas gangrene) involving the pelvic tissues and left leg. An
      unexpected finding was the presence of histologically distinct bilateral renal
      cell carcinomas. Neither gas gangrene nor renal cell cancer has been reported
      previously in association with sacral chordoma.

PMID- 8859614
TI  - Transformation of residual mature ovarian teratoma to adenocarcinoma 10 years
      after initial treatment.
AB  - A patient with a residual mature solid ovarian teratoma, which underwent
      malignant transformation to an adenocarcinoma 10 years after previous successful
      treatment, is presented. This case history illustrates that patients with
      residual mature disease require long term follow-up.

PMID- 8859615
TI  - Clinical Oncology Information Network: is the need urgent?

PMID- 8859616
TI  - Non-surgical management of early breast cancer in the United Kingdom:
      radiotherapy fractionation practices.

PMID- 8859617
TI  - Thromboembolic events with paclitaxel.

PMID- 8859722
TI  - Transient induction of E-selectin expression following TNF alpha-based isolated
      limb perfusion in melanoma and sarcoma patients is not tumor specific.
AB  - Endothelial injury of the tumor microvasculature after isolated limb perfusion
      (ILP) with TNF-alpha and melphalan is considered to play an important role in the
      pathogenesis of tumor necrosis. It is thought to follow endothelial cell
      activation and subsequent attraction of polymorphonuclear cells (PMNs). The
      observed selectivity for the tumor could be due to preferential overexpression of
      cell-adhesion molecules by the tumor vasculature. We tested this proposition by
      analyzing sequential biopsies from both tumor and normal distant skin, taken from
      melanoma and sarcoma patients before ILP and at 30 min and 24 h after ILP.
      Histopathologically confirmed complete response was observed in six of seven
      melanoma patients, 1-8 months after ILP. By using immunohistochemistry on the
      light- and electron-microscopic level, the expression patterns of intercellular
      adhesion molecules-1 (ICAM-1), E-selectin (ELAM-1), VCAM-1, and PECAM-l were
      examined. In addition, the results were compared with the effects on HUVECs
      (human umbilical vein endothelial cells) in vitro of transient exposure of the
      agents used during ILP. ICAM-1 and PECAM-1 were constitutively expressed on
      vascular endothelial cells, both in normal tissues and in the tumor lesions. In
      biopsies taken 30 min after termination of the perfusion, a moderate induction of
      E-selectin expression on the vascular endothelium in the tumors and a marked
      expression on the vasculature in the perfused normal skin were observed. It
      decreased within 24 h after perfusion in both normal skin and in the tumor. The
      upregulation of E-selectin was accompanied neither by an influx of neutrophils
      nor by hemorrhagic necrosis. There were no drastic changes in the expression of
      VCAM-1, ICAM-1, or PECAM- 1. These findings imply that the upregulation of E
      selectin after ILP is not restrfcted to the tumor microvasculature and that,
      therefore, these microvascular events seem not to be the decisive pathomechanism
      responsible for tumor regression.

PMID- 8859723
TI  - Generation of the complement activation product C5a precedes interleukin-2
      induced capillary leakage syndrome.
AB  - Capillary leakage syndrome (CLS) is a severe side effect of intravenous
      interleukin-2 (IL-2) therapy. Twenty-seven cycles of IL-2 therapy [six (day 1),
      nine (day 2), and 12 >( 10(6) U/m(2) body surface (days 3 to 5), given as
      continuous infusion] were analyzed in children and adolescents. The anaphylatoxin
      C5a was assessed as an early predictor for CLS. CLS developed in 11 of 27 cycles
      of IL-2 infusion. C5a at day 2 of IL-2 infusion (0.8-9.43 mu g/L; median, 1.8 mu
      g/L) was increased in CLS patients when compared with baseline values (0.21-0.74
      mu g/L; median, 0.40 mu g/L; p = 0.01) and when compared with C5a at day 2 in non
      CLS patients (0.44-1.2 mu g/L; median, 0.62 mu g/L; p <0.01). Ten of 11 CLS
      patients showed C5a levels >1.0 mu g/L, whereas 14 of 16 patients who did not
      develop CLS showed C5a <1.0 mu g/L (predictive value positive 83% for CLS).

PMID- 8859724
TI  - Combination therapy with interferon-gamma and interleukin-2 for the treatment of
      metastatic melanoma.
AB  - The toxicity and clinical response to treatment with the combination of
      interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic
      melanoma was evaluated. From May 1993 through February 1994, 20 patients were
      treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of
      subcutaneous IFN-gamma alone was administered to cohorts of two or three patients
      each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating
      doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.)
      administration of IL-2 (720,000 IU/kg) given three times a day. A treatment
      course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated
      by a 10-day interval. Five additional patients were treated with five courses of
      IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated
      had the diagnosis of metastatic melanoma. The maximal tolerated dose of
      subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting
      hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of
      MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received
      the combination of IFN-gamma and IL-2 had responses, one partial and one complete
      response. The duration of response was 7 months for the partial response and 12
      months for the complete response. IFN-gamma was tolerated with minimal side
      effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased
      toxicities were found with the combination treatment, as compared with IL-2
      alone. One death occurred on the third day of treatment with IFN-gamma alone from
      hemorrhage into brain metastases. There were no responders in the five patients
      who received the combination treatment of TIL, IL-2, and IFN-gamma. From these
      findings, we conclude that further studies looking at this combination treatment
      are not warranted.

PMID- 8859725
TI  - Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of
      metastatic adenocarcinoma patients undergoing active specific immunotherapy with
      synthetic STn vaccine.
AB  - The humoral immune response of 85 metastatic breast, ovarian, and colorectal
      cancer patients was analyzed after immunization with THERATOPE STn-KLH (KLH,
      keyhole limpet hemocyanin) cancer vaccine emulsified in DETOX adjuvant. Enzyme
      linked immunosorbent assay (ELISA) antibody titers against the synthetic sialyl
      Tn (STn) epitope were estimated by using solid phase STn-HSA and compared with
      antibody titers generated to the more biologically relevant natural mucin STn
      epitopes by using ovine submaxillary mucin (OSM) as a solid phase. Anti-KLH
      antibody titers were compared with anti-STn antibody titers as a specificity
      control. All but two patients generated increased anti-OSM antibody titers after
      immunization with STn-KLH. Breast and colorectal cancer patients who had the
      highest anti-OSM antibody titers, determined 4 weeks after the fourth
      immunization with STn-KLH (post-4 ASI), survived longer than the patients who had
      lower post-4 active specific immunotherapy (ASI) anti-OSM antibody titers. In
      contrast, there was no correlation of anti-KLH antibody titers with survival,
      demonstrating the specificity of the association of anti-OSM antibodies with
      survival. Cox multivariate survival analysis models were used to attempt to
      determine whether the induction of high-titer antibodies after immunization is a
      prognostic indicator independent of age, level of various tumor markers, extent
      of disease, lactate dehydrogenase (LDH) level, and route of administration of low
      dose cyclophosphamide before ASI. Increased pre-ASI CA-125 serum levels in the
      ovarian cancer patients were predictors of poor survival, independent of all of
      the other prognostic factors. The postimmunization increase in anti-OSM
      immunoglobulin M (IgM) titer was independently associated with longer survival of
      the colorectal cancer patients. Increased anti-OSM IgG titers were associated
      with a marked increased survival of the breast cancer patients, which was
      independent of all other prognostic factors except the size of measurable
      metastatic lesions at trial entry and the route of administration of
      cyclophosphamide. In a randomized trial design, breast cancer patients who
      received low-dose intravenous cyclophosphamide just before ASI showed longer
      survival and generated higher anti-OSM antibody titers than did patients who
      received low-dose oral cyclophosphamide before ASI.

PMID- 8859726
TI  - Immunomodulatory effects of interleukin-2 and interleukin-4 in patients with
      malignancy.
AB  - A phase I trial of simultaneously administered recombinant interleukin-2 (rIL-2)
      and recombinant human IL-4 (rHuIL-4) was conducted to evaluate the toxicity and
      the clinical and immunologic effects of this cytokine combination. Thirty-nine
      eligible patients with refractory malignancy were treated at eight different dose
      levels (1A to 3B): 1-3 of rIL-2 [3.0, 12.0, and 48.0 x 10(6) IU/m(2) i.v. three
      times weekly (TIW)] and A-C of rHuIL-4 (40, 120, and 400 mu g/m(2) s.c. TIW). The
      toxicity of these two cytokines was moderate and was comparable with that seen
      with rIL-2 alone. The maximal tolerated dose (MTD) of the combination was not
      reached because of lack of sufficient rHuIL-4 but is at least 48.0 x 10(6)
      IU/m(2) of rIL-2 and 120 mu g/m(2) of rHuIL-4. Two patients with melanoma had
      partial responses. The immunologic effects included increases in absolute
      lymphocyte numbers, and the CD3- /CD56+/ CD2+, total CD56+, CD8+, and CD16c+
      lymphocyte subsets with increasing rIL-2 dose levels, but not with rHuIL-4. This
      increase in natural killer (NK) cells in the peripheral blood was accompanied by
      an increase over baseline in NK lytic activity against K562 targets; however,
      concomitant increases in lymphokine-activated killer (LAK) activity (Daudi
      targets) were not seen. The CD3+, CD4+, and CD3+/CD25+/HLA-Dr+ T-cell subsets
      also increased, and these increases were related to both increasing rIL-2 and
      rRuIL-4 doses. Finally, in four of six patients, serial tumor biopsies
      demonstrated increases in major histocompatibility complex (MHC) class I or II
      antigen expression on tumor cells or increasing T-cell infiltrates during
      cytokine therapy or both. This trial demonstrated that rIL-2 and rHuIL-4 can be
      administered simultaneously with acceptable toxicity. The immunologic findings
      demonstrated the expected rIL-2-associated increases of CD56+ and CD16c+
      lymphocytes and NK activity, and interestingly, no development of LAK activity.
      These findings suggest regulatory effects of rHuIL-4 on rIL-2-related effects in
      vivo.

PMID- 8859727
TI  - Vitiligo in patients with melanoma: normal tissue antigens can be targets for
      cancer immunotherapy.
AB  - Patients with metastatic renal cell cancer and metastatic melanoma treated with
      high-dose interleukin-2-based immunotherapy were prospectively evaluated for the
      development of vitiligo. All patients seen in the Surgery Branch, NCI
      Immunotherapy Clinic, who had been followed for at least 1 year were evaluated.
      Of 104 patients with metastatic renal cancer none developed vitiligo, though
      vitiligo was seen in 11 of 74 (15%) patients with metastatic melanoma (p2 =
      0.0001). No vitiligo was seen in 27 patients who did not respond to
      immunotherapy, although vitiligo was seen in 11 of 43 (26%) melanoma patients who
      had an objective response to IL-2-based immunotherapy (p2 = 0.0002). These
      findings provide further evidence that the presence of a growing melanoma can
      sensitize patients to melanocyte-differentiation antigens and that the immune
      response against these antigens is associated with cancer regression in patients
      undergoing immunotherapy.

PMID- 8859775
TI  - Altered mucin core peptide immunoreactivity in the colon polyp-carcinoma
      sequence.
AB  - Altered mucin glycosylation occurs in colonic adenomas and can correlate with
      risk for malignant transformation. The purpose of this study was to determine if
      immunoreactivity of core tandem repeat peptides of specific mucin genes
      correlates with histopathologic criteria of malignant potential in the colon.
      Expression of MUC1, MUC2, and MUC3 core tandem repeat proteins was examined in
      specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous
      polyps (n = 89), and invasive cancer (n = 19). An immunohistochemical scoring
      system that takes into account specimen heterogeneity and yields an integrated
      numerical score subject to statistical analysis was used. RNA message levels from
      tubular and tubulovillous adenomas (n = 13), normal colon (n = 12), and
      moderately differentiated adenocarcinomas (n = 8) were determined using RNA slot
      blot analysis with mucin-specific cDNA probes. MUC1 staining was rarely present
      in normal colon. MUC2 immunoreactivity was limited to goblet cells in most normal
      colonic crypts, and MUC3 staining was weakly expressed in the upper crypt regions
      only. In comparison with normal and hyperplastic specimens, MUC1 and MUC3
      immunoreactivity scores were significantly increased in adenomas of increasing
      villous histology, size, and dysplasia. MUC2 scores were significantly increased
      in adenomas of greater villous histology and size. Comparable MUC1, MUC2, and
      MUC3 mRNA levels were present in adenomas and normal colon, whereas mucin mRNA
      levels were decreased in adenocarcinomas. We conclude that enhanced
      immunoreactivity of MUC1, MUC2 and MUC3 mucin tandem repeats occurs in
      adenomatous polyps and is associated with an increased risk for malignant
      transformation.

PMID- 8859776
TI  - Immunohistochemical studies of activated matrix metalloproteinase-2 (MMP
      2a)expression in human prostate cancer.
AB  - Previous immunolabeling studies have indicated that increased expression of the
      matrix metalloproteinase-2 (MMP-2) zymogen is associated with an increased
      Gleason score for human prostate cancer. In the accompanying paper, we have found
      by immunoblotting and ELISA that the MMP-2 enzyme (termed MMP-2a) is expressed in
      prostate cancer and that increased expression is associated with progression.
      Monoclonal antibodies specific for MMP-2a were used to investigate the expression
      of MMP-2a in human prostate tissue sections of benign and malignant cancers.
      Immunohistochemistry indicated that MMP-2a expression was undetectable in fetal
      (n = 4), benign (n = 11), and low Gleason score 4 (n = 8) tissue. MMP-2a was
      faintly expressed (+) in cancer assigned Gleason scores 5 (n = 20) and 6 (n =
      13). In comparison, MMP-2a was expressed at an intermediate level (++) in tissues
      of Gleason score 7 (n = 24), and at a intense level ( to +) in tissues of score 8
      (n = 48), 9 (n = 9) and 10 (n = 35) and in lymph node metastases (n = 10). These
      observations were confirmed by quantitative Computer Assisted Imaging Analysis.
      In general, MMP-2a was primarily expressed by the glandular epithelial cells, and
      in high Gleason score 10 specimens (n = 25/35) there was clear evidence of MMP-2a
      localization at the cell surface. These data suggest that increased MMP-2a
      expression may be associated with malignant progression and metastases.

PMID- 8859777
TI  - Evidence for increased activated metalloproteinase 2 (MMP-2a) expression
      associated with human prostate cancer progression.
AB  - Immunolabeling studies have previously indicated that increased expression of the
      72-kDa matrix metalloproteinase 2 (MMP-2) is associated with human prostate
      cancer progression. It is not known if the enzymatically active MMP-2 is
      expressed in prostate cancer and if increased expression is associated with
      progression. Monoclonal antibodies specific for the activated MMP-2 molecule (MMP
      2a, 66 kDa) were used (along with previously developed MMP-2 antibodies) to
      investigate the expression of MMP-2a and MMP-2 in human prostate tissue extracts.
      SDS-PAGE, Western blots, and zymography indicated that MMP-2a expression was
      undetectable in normal prostate (n = 6), benign prostatic hyperplasia (n = 9),
      and in prostate cancer of low Gleason score (GS) 4 (n = 11). MMP-2a was expressed
      in prostate cancer of increased GS (n = 37) and in lymph node metastases (n = 7).
      Quantitative ELISAs of human prostate cancer tissue extracts revealed that the
      levels of MMP-2 and MMP-2a per microgram of protein increased in prostate cancer
      tissues of increased GS (n = 48). MMP-2a levels were also high in prostatic lymph
      node metastases, but MMP-2 was not expressed or was barely detectable in these
      tissues. The molar ratios of MMP-2a to MMP-2 increased from 0 to 6.23 in tissues
      of GS 4 to 10, respectively. We conclude that significant increases in MMP-2a are
      associated with the malignant progression of prostate cancer and with tumor cell
      metastases to lymph nodes.

PMID- 8859778
TI  - 2-deoxy-D-glucose toxicity and transport in human multidrug-resistant KB
      carcinoma cell lines.
AB  - It is shown that a series of colchicine-selected multidrug-resistant (MDR) human
      KB carcinoma cell lines displayed increasing 2-deoxy-D-glucose collateral
      sensitivity, which correlated with increasing multidrug resistance. The relative
      resistance of MDR cell lines to 2-deoxy-D-glucose was reduced to 0.73 (KB-8-5),
      0.3 (KB-8-5-11) and 0.2 (KB-C1) when compared with parental KB-3-1 (1.0). 2-Deoxy
      D-glucose accumulation was found to be reduced in the MDR cell lines in a manner
      that correlated with 2-deoxy-D-glucose collateral sensitivity. At 30 min 2-deoxy
      D-glucose accumulation was reduced to 0.61 (KB-8-5), 0.41 (KB-8-5-11) and 0.22
      (KB-C1) relative to KB-3-1 uptake (1.0). The efflux of 2-deoxy-D-glucose was not
      significantly different between resistant and sensitive cell lines. Analysis of 2
      deoxy-D-glucose uptake kinetics, by initial rate measurements, showed alterations
      in K(t) and J(max) for MDR when compared with KB-3-l cells. The levels of GLUT-1
      facilitative transporter were found to be reduced significantly in the MDR cell
      lines in total cell homogenate and plasma membrane fractions by using Western
      blot analysis. Changes in the plasma membrane level of GLUT-1 correlated with 2
      deoxy-D-glucose toxicity and uptake for MDR cell lines, where relative GLUT-i
      levels were reduced to 0.71 (KB-8-5), 0.43 (KB-8-5-1 1) and 0.27 (KB-Cl) relative
      to KB-31(1.0). It is concluded that the response of human KB MDR cells to 2-deoxy
      D-glucose involved alterations in the level and activity of the facilitative
      glucose transporter, GLUT-1, in a manner that is associated with the degree of
      multidrug resistance.

PMID- 8859779
TI  - Transgenic mice carrying the human KRAS oncogene under the control of a
      thyroglobulin promoter: KRAS expression in thyroids analyzed by in situ
      hybridization.
AB  - We have previously generated transgenic mice bearing a molecular construct
      obtained by fusing the rat thyroglobulin promoter with the human Kirsten ras
      oncogene (KRAS). These mice showed thyroid abnormalities, although at very low
      incidence and after a long latency period. A six-month thyrotropin (TSH)
      stimulation of thyroid glands, followed by a two-month suspension, induced a
      significant increase in the number of lesions in transgenic mice as compared with
      a nontransgenic control group. Our goal was to follow the progression and the
      reversion of the tumorigenesis process in relationship with the levels of
      expression of the KRAS in this experimental model. In situ hybridization was used
      to detect expression of KRAS mRNA in sections of thyroids of the various groups
      of mice. A positive hybridization was observed in follicular cells of TSH
      stimulated transgenic mice, whereas no expression could be appreciated in control
      nontransgenic mice. A positive signal was also observed in thyroid glands excised
      from transgenic mice after the 2-month suspension of treatment; however, the
      number of expressing cells was decreased compared with transgenic mice killed
      immediately after 6 months of a goitrogen regimen. Finally, every cell in the
      single thyroid carcinoma observed after the two-month suspension was positive for
      the transgene mRNA. This study further strengthens the role of the expression of
      mutated KRAS in the early stages of thyroid follicular cell transformation and
      indicates that when the expression of the mutated KRAS becomes independent of
      exogenous TSH stimulation, this event coincides with a further progression
      towards tumorigenesis.

PMID- 8859780
TI  - Superior cytotoxic potency of mitoxantrone in interaction with DNA: comparison
      with that of daunorubicin.
AB  - The mechanism of action of the anthraquinone antileukemic drug mitoxantrone (MIT)
      was investigated and compared with that of daunorubicin (DNR) with emphasis on
      the interaction with DNA to clarify the more potent cytotoxic activity of MIT
      than DNR in human leukemia cells. MIT showed similar characteristics to those of
      the anthracyclines such as DNR in that binding of MIT to DNA was associated with
      reduced template activity and cleavage of DNA in HL-60 human leukemia cells.
      However, as compared with DNR, MIT showed an increased number of binding sites on
      DNA, a lower inhibition constant for DNA polymerization, and a greater DNA
      cleavage activity. These properties may contribute to its greater potency than
      that of DNR, with which MIT inhibited the proliferation of HL-60 human leukemia
      cells.

PMID- 8859887
TI  - Postnatal development of cell types in the hamster Harderian gland.
AB  - The morphology, frequency, and distribution of mitotic cells in the epithelium of
      the Harderian gland was studied in the male and female hamster from birth to the
      ninetieth day of postnatal life using light and electron microscopic techniques.
      The results obtained show that there is a gradual decline in the mitotic activity
      of the Harderian gland as the animals become older which continues until sexual
      maturity is reached. The study did not find any morphological evidence for the
      existence of separate precursor cells for the different secretory cell types of
      the gland. Secretory cells seem to be a homogeneous population in the glands of
      hamsters younger than 20 days. Cells that could be interpreted as
      undifferentiated stem cells were not observed. Mitotic cells were observed
      randomly distributed within tubulo-alveoli, similar to those in interphase. The
      first sex differences were observed at day 20, when type II cells appeared in
      male glands. From this point, the percentage of type II cells rapidly increased
      in male glands. This increase was not accompanied by an increase in the global
      mitotic activity. However, at this age, male type II cells develop an intense
      mitotic activity. The observations obtained are in accordance with the hypothesis
      that the type I and type II cells have the same cell precursor.

PMID- 8859888
TI  - Invasive processes in the normal Harderian gland of Syrian hamster.
AB  - In this contribution we will pay special attention to several morphological
      findings that we can observe, under some circumstances, in the normal Harderian
      gland of the Syrian hamster. The accumulation of porphyrins in this gland results
      in mitochondrial damage and extensive cell death. Many damaged cells are secreted
      into the lumen of the tubule-alveoli, but most of them seem to produce an
      invasive process that even affects the vascular components of the gland. In this
      way, many blood vessels are invaded and appear partially filled with the invasive
      mass, which sometimes totally occludes the lumen of the vessels. We have also
      observed other surprising features related to a special kind of activity in
      certain secretory cells. Such activity results in a peculiar "segregation" of a
      cytoplasmic fragment, containing the nucleus. The affected cells seem to gather
      up their cytoplasm and nucleus towards the basal zone, while the rest of the
      cell, including practically the whole amount of lipid droplets, is relegated to
      the vicinity of the lumen. All these phenomena seem finally to result in the
      detachment of some clusters, composed of a limited number of cells, which display
      a basophilic cytoplasm practically free of lipid droplets.

PMID- 8859889
TI  - Regulation of the aminolevulinate synthase gene in the Syrian hamster Harderian
      gland: changes during development and circadian rhythm and role of some hormones.
AB  - The Syrian hamster Harderian gland has been advocated as a model to study the
      porphyrin biosynthetic pathway, since it shows by far the highest porphyrin
      concentration known to date. Another particular characteristic is the sexual
      dimorphism at both the morphological and the biochemical levels. We found a
      variation in the ALV-S (aminolevulinate synthase) gene expression according to
      sex, with females exhibiting much higher mRNA levels than do males. After
      castration, ALV-S mRNA rose considerably in males, this increase being inhibited
      by darkness or treatment with melatonin. Treatment with hCG or progesterone did
      not vary the ALV-S mRNA levels in females. Castrated males, however, showed a
      much larger increase when they were treated with hCG. No variations have been
      found in the expression of the ALV-S gene in female HG throughout the estrous
      cycle. During development, males and females showed similar ALV-S mRNA levels
      until they were 20 days old. Afterwards, they started showing gender-associated
      differences. In females, ALV-S mRNA levels rose during the first 3 months of
      life, and thereafter they decreased progressively with aging. A circadian rhythm
      has been found in the gene expression of ALV-S mRNA in females, showing very low
      levels in the morning and reaching a peak during the first hours of darkness. It
      was an endogenous rhythm, probably regulated at the transcriptional level. It is
      proposed that the light-dark period duration modulates this rhythm through the
      suprachiasmatic nucleus which in turn acts on the pineal secretion of melatonin
      that regulates ALV-S gene expression.

PMID- 8859890
TI  - Sexual diversity of the lipid metabolism in the Harderian gland of the golden
      hamster.
AB  - Fatty acid and alkyl compositions of 1-alkyl-2,3-diacylglycerols (ADG) in the
      Harderian gland of the golden hamster were determined. Fatty acids of male ADG
      consisted of straight chain saturated acids ranging from C12 to C22. Both even-
      and odd-numbered acids were observed, indicating that acetyl- and propionyl-CoAs
      were equally used as primers in the fatty acid synthesis. In female ADG a large
      amount of iso- and anteiso-branched fatty acids were detected. Odd-numbered acids
      (C15, 17, 19, and 21) contained iso- together with anteiso-branchings, and even
      numbered acids (C16 and 18) contained iso-branchings. These findings suggested
      that isobutyryl-, isovaleryl-, and 2-methylbutyryl-CoAs were used as primers in
      addition to acetyl- and propionyl-CoAs in fatty acid synthesis in the female
      gland. Such unusual primers are catabolic intermediates of valine, leucine, and
      isoleucine, respectively. Male ADG contained straight chain saturated alkyl
      residues ranging from C14 to 21. In the case of female ADG, though the main
      component was C18:O, most alkyl components had branchings at the iso- and anteiso
      positions. NMR data suggested the presence of propionic acid at the C3 position
      of glycerol in the male ADG and of isovaleric and 2-methylbutyric acids at the
      same position in the female ADG. These results suggest that the sexual
      differences of the lipids in the Harderian gland of the golden hamster are
      determined at the step of fatty acid synthesis depending on the available
      precursors in the male and female glands. We speculate that sex hormones affect
      the metabolism of branched chain amino acids and bring about the dramatic
      diversities of the lipid compositions in the male and female glands.

PMID- 8859892
TI  - Instrumental effects on in situ electrochemical STM studies: an investigation of
      a current surge induced Pd deposit on HOPG.
AB  - Knowledge of instrumental complications is vital both in interpreting
      experimental observations and in achieving true results. In a study of palladium
      electrodeposition on highly ordered pyrolytic graphite by in situ electrochemical
      scanning tunnelling microscopy, some unexpected experimental artefacts caused by
      instrumental design and tip-surface interactions have been recognised. The
      electrodeposition system employed in our in situ studies has been found to be
      very sensitive to an initial cathodic current surge when the potentiostat control
      was applied to the electrodes at the measured open circuit potential. As a
      result, palladium and/or hydrogen were immediately deposited on the graphite
      surface within a small radius under the imaging tip. The cause of this current
      surge was investigated and found to be related to the performance of the
      potentiostat. The deposit was removed either by anodic potential sweeps or under
      positive local electric fields of the imaging tip. Further cathodic deposition
      was possible on the surge-induced deposit. Characterisation, by ex situ x-ray
      diffraction, atomic force microscopy, scanning transmission electron microscopy
      and high resolution electron microscopy, showed that the deposits were Pd. Use of
      the various techniques demonstrated their complementarity in studies of the
      structure and dimensions of surface deposits.

PMID- 8859891
TI  - In vivo calcineurin crystals formed using the baculovirus expression system.
AB  - Calcineurin is a heterodimeric phosphatase involved in the signal transduction of
      antigen-activated T cells. Coexpression of its two subunits, the regulatory
      subunit from human and the catalytic subunit from Neurospora crassa in cultured
      insect cells using the baculovirus expression system results in the formation of
      very large crystals in the cytoplasm. The crystals are formed initially in
      vesicles, but their subsequent growth appears to be uninhibited and continues
      without the need of an enclosing membrane until the host cell lyses. Although
      these in vivo crystals are low in population, ranging only 0-3 per cell, they are
      extremely large, over 10 mu m in some cases. Biochemical assays confirm their
      calcineurin origin, with the regulatory subunit incorporated being myristoylated,
      although both the myristoylated and unmyristoylated forms are expressed. The
      lattice structure of the in vivo crystals, with a spacing of 5.5 nm, is preserved
      with the regular electron microscopic (EM) specimen preparation procedure.

PMID- 8859893
TI  - Transcriptional regulation and cell specificity determinants of the rat nicotinic
      acetylcholine receptor alpha 3 gene.
AB  - The effects of increased cAMP level and reduced protein kinase C activity on
      transcription of the alpha 3 neuronal nicotinic acetylcholine receptor (nAChR)
      gene in PC12 cells were examined. Two nAChR alpha 3 transcripts (3.9 and 2.4 kb)
      are expressed in PC12 cells. When PC12 cells were grown in 2 mu m phorbol 12
      myristate 13-acetate (PMA) for 2 days to lower protein kinase C activity, the
      levels of both transcripts were increased. When PC12 cells were grown in 5 mu m
      forskolin, the level of the 3.9 kb transcript was increased. We previously
      constructed clones containing promoter elements located upstream of the alpha 3
      gene which allow reporter gene expression in PC12 cells. These constructs were
      transfected into PC12 cells grown in PMA or forskolin. The increase in alpha 3
      transcripts in response to PMA or forskolin was shown to be mediated at least in
      part at the transcriptional level by elements located within 600 nucleotides of
      the transcriptional start sites. The promoter constructs were also used to
      demonstrate that elements needed to restrict the expression of alpha 3 in non
      neuronal cells lie near to the 5' end of the alpha 3 gene.

PMID- 8859894
TI  - Injections of okadaic acid, but not beta-amyloid peptide, induce Alz-50
      immunoreactive dystrophic neurites in the cerebral cortex of sheep.
AB  - In an attempt to produce an animal model of neurofibrillary degeneration of the
      Alzheimer type, okadaic acid (a phosphatase inhibitor) and beta-amyloid peptide
      (1-40) were microinjected into the cerebral cortex of six adult sheep. After
      survivals varying from 1 day to 3 months, the injection sites and adjacent areas
      were evaluated using light microscopic immunocytochemistry. Near sites of
      implantation of crystalline okadaic acid, the Alz-50 monoclonal antibody stained
      twisted, dystrophic neurites. None of the beta-amyloid peptide injections caused
      neurofibrillary pathology. However, immunohistochemical analysis revealed no
      detectable beta-amyloid peptide remaining in the neuropil, even at 1 day,
      indicating rapid clearance of the beta-amyloid peptide. The induction of Alz-50
      immunoreactive dystrophic neurites by okadaic acid in sheep represents a novel
      animal model of Alzheimer's neurofibrillary pathology.

PMID- 8859895
TI  - Effect of cutting the optic nerve on K+ currents in endfeet of Muller cells
      isolated from frog retina.
AB  - Membrane currents were recorded from Muller cells isolated from normal retinas
      and from retinas whose ganglion cell axons had been cut in the optic nerve 30-60
      days previously. The surgical procedure did not block the retinal blood supply
      and did not allow the axons to regenerate. The principal finding was that after
      severing the optic nerve there was less inward rectification in response to
      voltage commands. That is, the maintained inward current (I K(IN)) produced in
      response to a hyperpolarizing voltage command decreased leading to a decrease in
      the ratio I K(IN)/I K(OUT) In 98 mM [K+]O, this ratio was 2.86 +/- 0.21 (mean +/-
      SE; n = 24) in controls and 1.13 +/- 0.13 (n = 21) in Muller cells from
      denervated retinae. Barium, a blocker of the potassium inward rectifier (I
      (KIR)), eliminated this difference. Moreover, severing the optic nerve also
      decreased the resting potentials of Muller cells in 2.5 mM [K+]O from -83 +/- 7
      mV to -63 +/- 9 mV. The results suggest that the voltage-dependent behavior and
      selectivity of K+ inward rectifying channels (K (ir)) in the endfeet depends on
      the integrity of the closely apposed ganglion cells.

PMID- 8859896
TI  - Intracarotid tumor necrosis factor-alpha administration increases the blood-brain
      barrier permeability in cerebral cortex of the newborn pig: quantitative aspects
      of double-labelling studies and confocal laser scanning analysis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a crucial role in the pathogenesis
      of the central nervous system infections. The aim of the present study was to
      analyze quantitatively the changes in the blood-brain barrier (BBB) permeability
      after the intracarotid injection of TNF-alpha. Recombinant human TNF-alpha was
      injected into the left internal carotid artery of anesthetized newborn pigs (n =
      48) in the doses of 0, 1000, 10 000 and 100 000 IU, respectively. Before, as well
      as 1, 2, 4, 8, and 16 h after the challenge, the extravasation of a small (sodium
      fluorescein (SF), mw 376), and a large (Evan's blue-albumin (EBA), mw 67 000)
      tracer was determined concomitantly by spectrophotometry in the cerebral cortex
      of the animals. There was a time- and dose-dependent increase in BBB permeability
      both for SF and EBA; however, significant (P < 0.05) BBB opening for albumin only
      developed 2 h after the challenge. In the morphological study the same excitable
      tracers, identical experimental protocol and groups were used. Cryostat sections
      of brain tissue were viewed for optical sectioning with a confocal laser scanning
      microscope equipped with an argon/krypton ion laser. A diffuse BBB opening for SF
      and a moderate perivascular extravasation for EBA were found in the cortices of
      TNF-alpha-treated animals. We conclude that significant increases in
      intravascular TNF-alpha-concentration during neonatal infections may result in
      vasogenic brain edema formation.

PMID- 8859897
TI  - Regional study of spinal alpha 2-adrenoceptor densities after intraspinal
      noradrenergic-rich implants on adult rats bearing complete spinal cord
      transection or selective chemical noradrenergic denervation.
AB  - One of the challenges of restorative neuronal transplantation in the CNS of
      mammals is the appropriate integration of grafted cells in the host circuitry.
      One key parameter is the specific influence of grafted cells upon corresponding
      receptors. In order to test this issue on the lesioned spinal cord of adult rats,
      two models of spinal cord denervation were used: the first one consisted of a
      complete transection 1 week prior to an intraspinal transplantation of embryonic
      locus coeruleus (LC) primordia cell suspension; the second one was a chemical
      destruction of the spinal noradrenergic (NA) system 1 month prior to a similar
      transplantation. Five weeks after transplantation, spinal sections were processed
      for autoradiographic quantification of alpha 2-adrenoceptor binding sites
      densities. In most regions, alpha 2-adrenoceptor densities remained comparable or
      higher than before graft; interestingly, in lumbar dorsal horn, lumbar
      intermediate zone and sacral distal dorsal horn of transected-grafted rats, they
      returned to control level. Results are discussed in relation to the parallel
      study performed concerning alpha 1-adrenoceptors.

PMID- 8859898
TI  - Increased neurite outgrowth of cultured rat dorsal root ganglion cells following
      transection or inhibition of axonal transport of the sciatic nerve.
AB  - Dissociated dorsal root ganglion cells (DRGs), taken from rats 2 weeks after
      sciatic nerve transection, have an increase in the percentage of cells with
      neurites compared to DRGs taken from normal animals. This study examines the
      possible factors that may contribute to the nerve injury-induced increase in
      neuritogenesis. Topical application of the local anaesthetic, bupivicaine, either
      to the nerve trunk prior to transection or to the proximal nerve stump for 2
      weeks had no effect on the increased neurite outgrowth induced by nerve
      transection. Neurite outgrowth was also not influenced by administration of
      either nerve growth factor (NGF) via the femoral artery into normal rats or anti
      NGF antiserum to the proximal nerve stump. Inhibition of axonal transport by
      topical application of vinblastine, however, induced a significant increase in
      neurite outgrowth compared to untreated controls. In addition, vinblastine
      treated animals also develop hyperalgesia to mechanical stimulation and
      transganglionic labelling of sensory neurons with choleragenoid-horseradish
      peroxidase shows that the area of termination of myelinated sensory neurons in
      the spinal cord expands into lamina II. The results suggest that nerve injury
      induced increase in neurite outgrowth is not dependent on NGF nor nerve impulses
      generated at the site of injury and supports the view that the absence of an
      inhibitory factor(s), that in normal animals may regulate neuronal outgrowth.

PMID- 8859899
TI  - Heterogeneity in the columnar number of neurons in different neocortical areas in
      the rat.
AB  - We have investigated the number of neurons in three neocortical areas of the rat
      brain. Our results challenge the uniformity concept proposed by Rockel et al.
      [Brain, 103 (1980) 221-244]. Area Fr1, HL and Oc2 (primary motor, primary
      somatosensory and secondary visual cortex) from Sprague-Dawley rats were
      examined. The brains were glutaraldehyde fixed, sectioned in 50 mu m thick
      sagittal slices and stained in Richardson's solution. The counting was carried
      out using a computerized system based on the optical disector. The cortical
      thickness was measured to be 1.9 mm, 1.9 mm, and 1.4 mm in area Fr1, HL, and Oc2,
      respectively. The number of neurons under 1 mm2 cortical surface was calculated
      to be 91 100 in Fr1, 133 500 in HL and 106 100 in Oc2. The number of neurons in a
      volume of tissue 30 x 25 mu m through the depth of the cortex was calculated to
      be 68 in Fr1, 100 in HL and 80 in Oc2. The density of neurons was calculated to
      be 48 500 neurons/mm3 in Fr1, 69 400 neurons/mm3 in HL and 76,900 neurons/mm3 in
      Oc2. There were significant (P < 0.01) differences between all areas regarding
      both the number of neurons under a certain area of surface as well as the neuron
      density. The results indicate that there is no basic uniformity in the number of
      neurons under a certain area of cortical surface.

PMID- 8859900
TI  - Astroglial cells inhibit the increasing permeability of brain endothelial cell
      monolayer following hypoxia/reoxygenation.
AB  - Blood-brain barrier (BBB) is known to be structured with astroglial cells (AGs)
      and brain endothelial cells (BECs), and it has been proposed that these cells
      play different roles in the BBB. We cultivated AGs and BECs from infant rats (2
      week-old), and these cells were cultured on the opposing side of collagen
      membrane to produce a co-culture model of the BBB in vitro. Permeability of the
      cell layer was evaluated by the electrical resistance through the membrane. To
      clarify the role of AGs in the BBB disruption following ischemia/reperfusion,
      electrical resistance of the co-culture model was compared to that of BEC
      monolayer following hypoxia/reoxygenation. The electrical resistance through BEC
      monolayer showed 55.5 +/- 15.1 percent reduction at 4 h of hypoxia, and 93.3 +/-
      5.4 percent reduction at 8 h of hypoxia (n = 8). However, the co-culture model
      showed attenuation of the reduction (24.8 +/- 14.2 percent) at 4 h of hypoxia (n
      = 8, P < 0.01), but not at 8 h of hypoxia (95.3 +/- 5.0 percent). These results
      indicate that AGs reduce the increasing permeability of the BEC monolayer
      following short duration of hypoxia/reoxygenation. It is suggested that AGs may
      have a protective effect to the BBB disruption following ischemia/reperfusion.

PMID- 8859901
TI  - Binding of botulinum type B neurotoxin to Chinese hamster ovary cells transfected
      with rat synaptotagmin II cDNA.
AB  - We have previously identified synaptotagmin, a synaptic vesicle membrane protein
      from rat brain, as a binding protein for Clostridium botulinum type B neurotoxin.
      In this report, rat synaptotagmin II was expressed by transfection in Chinese
      hamster ovary cells and interaction with the neurotoxin was studied. In stable
      transfectants, the NH(2)-terminal region of synaptotagmin was exposed to the
      extracellular medium. Synaptotagmin-expressing cells were shown to possess an
      extremely low binding activity for the radiodinated toxin. However, toxin-binding
      was markedly increased to cells which had been treated with gangliosides G T1b or
      G D1a. In synapses, the intravesicular NH(2)-terminus of synaptotagmin becomes
      exposed at the cell surface after following exocytosis. These findings suggest
      that the NH(2)-terminal domain of synaptotagmin II forms the binding site for
      type B neurotoxin by associating with specific gangliosides in presynaptic plasma
      membranes.

PMID- 8859902
TI  - Adenosine A1 receptor-dopamine D1 receptor interaction in the rat limbic system:
      modulation of dopamine D1 receptor antagonist binding sites.
AB  - Antagonistic interactions between adenosine A2a and dopamine D2 receptors and
      between adenosine A1 and dopamine D1 receptors have been previously found in the
      basal ganglia. Those interactions have been proposed to be key mechanisms of
      action responsible for the motor depressant effects of adenosine agonists and the
      motor activating effects of adenosine antagonists, like caffeine. By using
      quantitative receptor autoradiography, the selective adenosine A1 receptor
      agonist N6-cyclopentyladenosine was found to decrease the affinity of dopamine D1
      receptors for the specific D1 antagonist [(125)I]SCH 23982 in both the nucleus
      accumbens and the medial prefrontal cortex of the rat brain. The present results
      suggest that dopamine neurotransmission, through an A1-D1 interaction, might also
      he involved in the behavioural effects of adenosine agonists and antagonists not
      related to motor activity, like the sedative-hypnogenic properties of adenosine
      analogues and the psychostimulant effects of caffeine.

PMID- 8859903
TI  - Long-term effects of retinal lesions on growth-associated protein 43 (GAP-43)
      expression in the visual system of adult cats.
AB  - We have investigated the role of growth-associated protein 43 (GAP-43) in
      synaptic reorganization in the visual system of adult cats that received
      binocular central retinal lesions. Different survival times between 3 and 8
      months after induction of the lesion were chosen. In the deafferented part of the
      dorsal lateral geniculate nucleus (dLGN) we found a long-lasting increase in GAP
      43 protein, while glial fibrillary acidic protein (GFAP) immunoreactivity, which
      initially increased due to the degeneration of retinal ganglion cells, slowly
      subsided over this period. In area 17, the pattern of GAP-43 expression did not
      provide indications for morphological changes in the cortical architecture
      following retinal lesions.

PMID- 8859904
TI  - Sensory characterization of somatic parietal tissues in humans with chronic
      fatigue syndrome.
AB  - Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the
      musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle)
      versus superficial (skin, subcutis) sensitivity to pain was explored by measuring
      pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius
      and quadriceps and overlying skin and subcutis in comparison with normal
      subjects. Thresholds in patients were normal in skin and subcutis but
      significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all
      sites. The selective muscle hypersensitivity corresponded also to fiber
      abnormalities at muscle biopsy (quadriceps) performed in nine patients which were
      absent in normal subjects (four cases): morphostructural alterations of the
      sarchomere, fatty degeneration and fibrous regeneration, inversion of the
      cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and
      monstruosity of mitochondria, reduction of some mitochondrial enzymatic
      activities and increments of common deletion of 4977 bp of mitochondrial DNA 150
      3000 times the normal values. By showing both sensory (diffuse hyperalgesia) and
      anatomical (degenerative picture) changes at muscle level, the results suggest a
      role played by peripberal mechanisms in the genesis of CFS symptoms. They would
      exclude the heightened perception of physiological signals from all districts
      hypothesized by some authors, especially as the hyperalgesia is absent in
      skin/subcutis.

PMID- 8859905
TI  - Lack of nitric oxide sensitivity of carotid sinus baroreceptors activated by
      normal blood pressure stimuli in cats.
AB  - We examined the effects of inhibition of nitric oxide (NO) synthesis and local
      administration of NO-donors on baroreceptor activity in anaesthetized cats.
      Baroreceptor activity was assessed by measuring changes in the pulse synchronous
      carotid sinus nerve discharge in a modified blind sack preparation. Within
      physiological mean arterial blood pressure (BP) ranges (BP = 70-150 mmHg),
      neither abluminal (in a pool around the carotid sinus, n = 15) nor intravascular
      (via the A. lingualis, n = 10) administration of the NO-synthase inhibitor N(G)
      nitro-L-arginine (L-NNA, 30 mu M) significantly modulated baroreceptor activity.
      The NO donors S-nitroso-N-acetylpenicillamine, sodium nitroprusside and
      glyceryltrinitrate caused significant decreases in baroreceptor activity only
      when applied intravascularly at concentrations > or = 100 mu M. In contrast,
      prostacyclin (1 mu M, n = 5) attenuated and indomethacin (10 mu M, n = 5)
      enhanced baroreceptor activity significantly upon intravascular administration.
      Baroreceptor activity was also effectively inhibited by gadolinium (Gd(3+), 1
      mM). These results suggest that carotid sinus baroreceptor function in cats is
      rather insensitive to changes in the supply of endogenous or exogenous NO.

PMID- 8859906
TI  - Glycine activation of human homomeric alpha 1 glycine receptors is sensitive to
      pressure in the range of the high pressure nervous syndrome.
AB  - The effect of hyperbaric pressure on the inhibitory glycine receptor has been
      investigated in voltage-clamped Xenopus oocytes microinjected with cRNA encoding
      the human alpha-1 glycine receptor subunit. Heterologous expression of the human
      alpha-1 subunit generated functional glycine-gated channels with properties
      typical of native receptors. Glycine elicited a concentration-dependent inward
      current which reversed polarity at -25 mV and was antagonised by nanomolar
      concentrations of strychnine. Concentration-response curves established for the
      homomeric alpha-1 glycine receptor at 5, 10 and 15 MPa were progressively shifted
      to the right with respect to the concentration response curve established at
      atmospheric pressure (0.1 MPa). Pressure had no effect on the maximal response.
      The EC(50) values at 0.1, 5, 10 and 15 MPa were 190 mu M, 222 mu M, 338 mu M and
      482 mu M, respectively. The results demonstrate that a receptor comprised solely
      of the human alpha-subunit is sensitive to pressure in the range that affects
      divers and at which the native rat spinal cord receptor is affected. This finding
      is discussed in the context of the postulated binding sites for glycine and the
      implications for the design of drugs to protect divers from the effects of
      pressure.

PMID- 8859907
TI  - Chronic administration of methamphetamine does not affect the suprachiasmatic
      nucleus-operated circadian pacemaker in rats.
AB  - The effects of chronic administration of methamphetamine (MAP) on rat locomotor
      activity rhythm under light-dark (LD) housing and on neuronal activity rhythms
      from the suprachiasmatic nucleus (SCN) in vitro were investigated. Control rats
      exhibited an LD-entrained nocturnal locomotor rhythm. The firing rate of SCN
      neuronal activity was high during the light period and low during the dark period
      in control normal rats, and peak of firing activity occurred around zeitgeber
      time (ZT) 6. On the other hand, chronic MAP administration caused various
      disorganization of locomotor activity rhythms with a long free-running period (25
      35 h). Neuronal activity rhythms of the SCN were unaffected by chronic MAP
      administration, that is, high during the light period and low during the dark
      period. The present findings suggested that the SCN maintained as a circadian
      pacemaker even under chronic MAP administration which affected overt rhythms.

PMID- 8859908
TI  - Lack of Fos-like immunoreactivity after spontaneous seizures or reinduction of
      status epilepticus by pilocarpine in rats.
AB  - Acute seizures and status epilepticus induced by pilocarpine lead to the
      expression of Fos-like immunoreactivity in several specific brain areas in a
      manner similar to that of other models of limbic seizures. Upon development of
      status epilepticus after systemic pilocarpine injection, animals develop a state
      where chronic spontaneous seizures recur. Assessment of Fos-like immunoreactivity
      after such spontaneous seizures or after status epilepticus reinduction reveals
      either lack of staining or a weak reaction in a few brain areas including the
      ventral tip of the dentate gyrus, prepiriform, lateral piriform and perirhinal
      cortices, and scattered locations throughout temporal neocortex. Our results
      suggest that status epilepticus induction may lead to a long-lasting state of Fos
      down-regulation.

PMID- 8859909
TI  - Alterations in GAP-43-immunoreactive innervation in the aging rat pituitary.
AB  - The levels and distribution of the growth-associated protein, GAP-43, were
      examined in the pituitary glands of young and aging Sprague-Dawley rats, using
      immunohistochemical techniques on tissue sections and Western blot analyses. GAP
      43-immunoreactive innervation was observed in sections in the intermediate and
      neural lobes of animals aged 8-15 months, while in the oldest rats studied (17
      months), stained fibers were observed mainly in the neural, but not the
      intermediate lobe. Western blots revealed reduced levels of GAP-43 in samples
      from 15 month old animals, as compared to 12 month old rats, in the
      neurointermediate lobes. There was no immunoreactivity for GAP-43 in the anterior
      lobes in the tissue sections or in the blots in any of the glands examined. A
      diminished level of GAP-43 in pituitary innervation in aged animals suggests a
      reduced ability for nerve terminals to undergo 'plastic' changes in their
      relationship to target endocrine cells. Since GAP-43 has also been suggested to
      modulate neurotransmitter release, a reduction in the protein in aging nerve
      terminals may diminish availability of transmitters at presynaptic sites.

PMID- 8859910
TI  - Tachyphylaxis develops to bradykinin-induced plasma extravasation in the rat.
AB  - Bradykinin, an inflammatory mediator produced from plasma kallikreins, has potent
      effects on vascular functions, including increasing plasma extravasation and
      vasodilation. Attenuation in the response (desensitization to maintained exposure
      or tachyphylaxis to repeated administration) to bradykinin actions on synovial
      vasculature, a critical variable with respect to the role of bradykinin in
      sustained or chronic synovial inflammation, has not been elucidated. In the
      present study, we determined if tachyphylaxis and desensitization for bradykinin
      induced plasma extravasation in the knee joint occur. Bradykinin-induced plasma
      extravasation into the knee joint cavity was determined spectrophotometrically by
      measuring the concentration of Evans blue dye extravasation into the joint
      perfusate. To examine for the development of tachyphylaxis, perfusion of
      bradykinin (160 ng/ml) was repeated after a 40-min wash with normal saline.
      Continuous intra-articular perfusion of bradykinin produced an increase in plasma
      extravasation that remained relatively stable with only a small, approximately 15
      percent, decrease over 170 min. On the other hand, the levels of plasma
      extravasation produced by intermittent perfusion of bradykinin were dramatically
      lower than that induced by the first exposure (i.e., tachyphylaxis). We conclude
      that bradykinin-induced plasma extravasation develops marked tachyphylaxis but
      only minimal desensitization.

PMID- 8859911
TI  - Influence of referring physicians on interventions by a pediatric and neonatal
      critical care transport team.
AB  - The objective of this study was to determine the influence of: a) pediatrician
      versus nonpediatrician referrals on a transport team's therapeutic interventions
      and b) referring physician's year of graduation on interventions performed by the
      transport team. From November 1987 through December 1989 we prospectively
      compared the therapeutic interventions performed by the critical care transport
      team on newborns and pediatric patients with the referring physician's specialty
      and year of graduation. The transport team (critical care physician [PL3 or
      greater], registered respiratory therapist, critical care nurse), recorded all
      therapeutic interventions, including both procedural and pharmacologic, for 213
      newborn and 149 consecutive pediatric transports. Referring physicians were
      categorized as pediatricians and nonpediatricians. Data were analyzed by analysis
      of variance, chi2, or linear regression. All patients were admitted to either the
      pediatric or the neonatal intensive care unit, and over 80% of both age groups
      received assisted ventilation. Newborns referred by nonpediatricians required
      significantly more procedural interventions (2.64 vs 1.91, P = 0.016) than those
      referred by pediatricians. The opposite relationship was observed among pediatric
      patients in that children referred by pediatricians received more frequent
      intervention (P = 0.008) than those referred by nonpediatricians. There was a
      significant inverse relationship between the referring physicians year of medical
      school graduation and the number of therapeutic interventions (total
      interventions = 6.17 - 0.040 x graduation year, P = 0.01) and procedural
      interventions (procedural interventions = 3.54 - 0.024 x graduation year, P =
      0.01). We found that the referring physicians' medical training affected the
      number of interventions their patients received. Similarly, patients were likely
      to receive more interventions if the referral physicians training was not recent.
      These data have educational implications and support the concepts of continuing
      medical education, recertification, and maintenance of skills among physicians
      providing care to critically ill newborns and pediatric patients.

PMID- 8859912
TI  - An observational asthma study alters emergency department use: the Hawthorne
      effect.
AB  - The objective of this study was to document that an observational study decreases
      the use of the emergency department (ED) for asthma. Comparison of rates between
      an audit and prospective period were used at a regional referral pediatric
      hospital ED. A total of 526 asthma visits from February 12, 1992, to April 10,
      1992, were examined in an initial audit and compared to 725 visits during a
      prospective study from May 16, 1993, to September 29, 1993. A physician check
      list for medications and follow-up plans was utilized during the prospective
      study. The rate of repeat visits and admissions was compared between the audit
      and the prospective periods. In the audit, 422 asthma patients were seen, and
      there were 68 repeat visits within one week of the initial visit and 153
      admissions. For 29 of the 68 repeat visits there was no documentation that
      medication had been increased after the initial visit. No follow-up plans were
      recorded in 275 of the 526 visits. During the prospective period 668 children
      presented to the ED with asthma, and 346 were enrolled into the study on risks
      for repeat visits. There were 57 repeat visits and 89 admissions. The repeat
      visit rate during the prospective period was 9 and 8%, respectively, in the
      enrolled and nonenrolled subjects. The repeat visit and admission rate decreased
      during the prospective period as compared to during the audit by 39% (P = 0.004)
      and 58% (P < 0.0001), respectively. A possible explanation for the difference in
      admission and repeat visit rates between the audit and prospective study is that
      physicians' behavior may have been altered by the awareness that their behavior
      was being closely monitored during the study.

PMID- 8859913
TI  - Piercing injury hospitalization in children.
AB  - Injuries from piercing or cutting instruments or objects are commonly seen in the
      pediatric emergency department. In this study, we present the epidemiology of
      piercing injuries resulting in hospitalization. Medical records for a one-year
      period with E-codes 920.0-920.9 were reviewed for victim-related demographic
      data, anatomic injury location, vehicle of injury, treatment, and hospital
      charges. The Abbreviated Injury Scale (AIS) was used to ascertain injury
      severity. The most common vehicles of injury were glass (n = 24, 34%), nails (n =
      11, 16%), and needles (n = 10, 14%). The median AIS score was significantly
      higher for hand injuries compared to the sample median AIS. Piercing injuries
      from consumer-related products were associated with the highest AIS scores
      (median = 2.5). Although the mean AIS for all injuries was only 1.5, these
      injuries resulted in significant costs, with a mean hospitalization charge of
      $3884 +/- 3528. Surgical procedures under general anesthesia were required in 81%
      of the patients.

PMID- 8859914
TI  - A comparison of interventions to improve clinic follow-up compliance after a
      pediatric emergency department visit.
AB  - A randomized prospective study was made to compare two interventions to improve
      compliance with follow-up appointments (FA) after a pediatric emergency
      department (ED) visit. The study population was 253 patients and families seen
      during daytime hours at a large pediatric ED and who required follow-up for their
      diagnosed condition. A control group of patients were told to call the clinic for
      FA, an appointment group of patients were given a FA in the ED prior to discharge
      and written reminder, and an intense group of patients were given a FA in the ED
      prior to discharge, a written reminder; they were offered a work excuse, child
      care, and transportation assistance; they were sent mailed reminders and had
      attempts at telephone reminders. More patients in the appointment group (47%, P <
      0.001) and intense group (52%, P < 0.001) kept FA than the control group (24%).
      Attempted telephone contact was unsuccessful in 39% of the intense group. When
      telephone contact was successful, patients were more likely to keep FA (62 vs
      38%, P < 0.04). Families left to make their own FA did so only 32% of the time.
      Medical record review of ED and clinic visits for one year after intervention
      indicated no long-term behavior change in appointment-making behavior or ED use
      in any group. It was concluded that providing a convenient FA prior to ED
      discharge improves compliance with clinic follow-up. If telephone contact is
      successful, telephone reminders also improve compliance. If follow-up is
      recommended, the majority of patients do not make their own appointments. A one
      time intervention does not result in a long-term behavioral change in use of
      clinics or the ED.

PMID- 8859915
TI  - Diagnosis of whooping cough: a new era with rapid molecular diagnostics.
AB  - A rapid diagnostic procedure, which is based upon the polymerase chain reaction
      (PCR) genetic amplification technology, was utilized to establish the presence of
      Bordetella pertussis in nasopharyngeal washes from children. Overall, 14.7% of
      456 specimens were positive by either culture or the rapid assay. Culture and PCR
      were concordant for 62.7% of positive samples; PCR provided an additional
      increment of 37.3%. PCR-positive, culture-negative specimens were more likely to
      be found among older patients with more prolonged illness and previous
      erythromycin therapy (P < 0.01 for all three comparisons). As a single laboratory
      assay, PCR should be recognized as the current standard for diagnosis.

PMID- 8859916
TI  - Intraosseous needle: use of the miniature C-arm imaging device to confirm
      placement.
AB  - Intraosseous infusions are commonly used in pediatric emergencies. Although this
      technique is often lifesaving, significant complications can develop from
      incorrect needle placement. Current methods of evaluating needle position rely on
      the operator's experience with the procedure. We describe the use of a miniature
      C-arm imaging device to accurately confirm proper needle placement.

PMID- 8859917
TI  - Pneumomediastinum in childhood asthma.
AB  - The objective of this study was to examine the presentation and clinical course
      of patients with asthma and pneumomediastinum (PNMD). A retrospective chart
      review was performed from a computer-generated list of all patients discharged
      from an urban children's hospital between 1981 and 1991 with the diagnoses of
      asthma and PNMD. Thirty cases and 30 controls with asthma, matched for age and
      sex, were identified. The incidence of PNMD and asthma was 0.3%. Mean age was
      11.8 years with a male:female ratio of 1.15:1. Chest pain was reported in 27% of
      patients and 13% of controls (P = 0.17). There was no difference in presenting
      respiratory rate, heart rate, or systolic blood pressure between cases and
      controls, nor was there a difference in respiratory distress by modified Wood
      Downes scale. Fifty percent of patients had room air oxygen saturation measured
      at presentation. There was a significant difference in mean oxygen saturation
      between those with PNMD and those without (90.4 vs 94.1 %; P = 0.03).
      Subcutaneous emphysema was detected in 73% of cases versus none in controls (P <
      0.001; positive predictive value (PPV) = 100%). Sixty-seven percent of patients
      with PNMD had repeat radiographs during hospitalization. Of these x-rays, 85%
      showed no change in, improvement, or complete resolution of the PNMD. Three
      patients (15%) developed a small increase in the PNMD. No patient developed
      pneumothorax, pneumopericardium, or deterioration in cardiovascular status. PNMD
      is a rare complication of asthma. Subcutaneous emphysema was the most useful
      predictor of PNMD in asthma. Chest pain and diminished oxygen saturation should
      heighten suspicion. Further complications of PNMD were exceedingly rare, and all
      patients recovered uneventfully, suggesting that attention to excellent treatment
      for the acute exacerbation may be sufficient in most instances of PNMD.

PMID- 8859918
TI  - Arrhythmias after astemizole overdose.
AB  - Astemizole, a relatively new H1 blocker, has been reported to cause ventricular
      arrhythmias in the poisoned patient. We present two cases of astemizole
      poisoning, one with asystole followed by ventricular fibrillation occurring 11
      hours after ingestion treated with defibrillation and one with an isolated
      finding of a prolonged corrected QT interval. Electrocardiogram monitoring to
      detect conduction defects can identify patients at risk of developing life
      threatening arrhythmias.

PMID- 8859919
TI  - Pediatric pulmonary artery thromboembolism: an illustrative case.
AB  - Correct and early diagnosis, along with appropriate therapy, should limit
      mortality. In the pediatric population, signs and symptoms may be subtle. PE
      should be on the differential diagnosis in patients that present with dyspnea in
      association with significant risk factors, chest pain, or hemoptysis. PE may be
      missed if a high index of suspicion is not maintained. In a patient with a PE, an
      appropriate hypercoagulable workup (Table 1) needs to be considered prior to
      initiation of anticoagulation therapy. This case highlights the need for further
      awareness.

PMID- 8859920
TI  - Respiratory failure from corn starch aspiration: a hazard of diaper changing.
AB  - Corn starch powder is widely used for routine infant skin care as a substitute
      for talcum powder, as it is believed to have fewer respiratory hazards. We
      describe a one-month-old infant who presented to an emergency department with
      respiratory failure and a severe pneumonitis from aspiration of corn starch
      powder. The patient recovered after five days of mechanical ventilatory support.
      We conclude that careless use of corn starch for infant skin care can lead to
      accidental aspiration of this substance and severe respiratory disease.

PMID- 8859921
TI  - Acute hemorrhagic edema of infancy.

PMID- 8859922
TI  - Emergency department evaluation of a rapid assay for detection of cocaine
      metabolites in urine specimens.
AB  - We evaluated the Abuscreen ONTRAK assay for cocaine metabolites, a rapid
      immunoassay for the detection of cocaine metabolites in a pediatric emergency
      department (ED) setting. The ONTRAK uses a cutoff point of 300 micrograms/L for
      benzoylecgonine (BEC), cocaine's major urinary metabolite. One hundred and thirty
      two urine specimens obtained from infants, children, and adolescents whose
      clinical findings warranted toxicology screening were evaluated. The ONTRAK
      identified all 15 specimens with BEC values of 300 micrograms/L, but did not
      detect seven additional specimens positive for cocaine metabolites at
      concentrations less than 300 micrograms/L. One third of the positive specimens
      for cocaine metabolite identified by fluorescent polarization immunoassay (FPIA),
      cutoff point set at 80 micrograms/L, and confirmed by gas chromatography/mass
      spectrometry (GUMS), cutoff point 50 micrograms/L, were not detected by the
      ONTRAK. These false negative specimens were seen exclusively in young children,
      whose concentration of cocaine metabolite was less than the ONTRAK's cutoff
      value. The test was sensitive to drug concentration at or around the stated
      cutoff values. The ONTRAK test for cocaine metabolites, although both a sensitive
      and specific screening test for adolescents who smoke or snort cocaine, lacks the
      sensitivity to be a useful screening too[ for detecting cocaine metabolites in
      young children. Limitations of currently performed toxicology screening tests
      (ie, stated cutoff levels) may cause emergency physicians to miss most young
      children whose symptoms may he related to cocaine exposure.

PMID- 8859923
TI  - Conditions mistaken for child abuse: Part I.

PMID- 8859924
TI  - Transport case 1: a time to fly? A dilemma in pediatric transport.

PMID- 8859926
TI  - Enteral feeding pumps.

PMID- 8859925
TI  - Pediatric emergency medicine: legal briefs.

PMID- 8859927
TI  - Vomiting and anuria after bicycle accident.

PMID- 8859928
TI  - To what degree of an examination?

PMID- 8859929
TI  - Electrophysiological effects of clentiazem, a new Ca2+ antagonist, on rabbit
      hearts.
AB  - Electrophysiological effects of clentiazem, a new 1,5-benzothiazepine type Ca(2+)
      antagonist, were examined in comparison with those of diltiazem in excised rabbit
      heart preparations. In Langendorff-perfused hearts electrically driven at basic
      cycle lengths of 400-500 ms, clentiazem (10(-8)-10(-6)M) and diltiazem (10(-8)
      10(-6)M) caused a concentration-dependent prolongation of the atrio-His bundle
      conduction time (A-H interval) without affecting the His bundle-ventricular
      conduction time (H-V interval). The effects of clentiazem were equivalent to
      those of diltiazem. In isolated rabbit atrioventricular (A-V) node preparations
      electrically driven at 400- to 500-ms intervals, clentiazem and diltiazem at >10(
      6)M concentrations produced concentration-dependent decreases in action potential
      amplitude (APA), maximum rate of depolarization (V max), and shortened action
      potential duration at 20 and 50% repolarization (APD(20) and APD(50)), whereas
      APD(90) was little affected. Application of 10(-6)M clentiazem prolonged
      effective refractory period (ERP) of the A-V node by approximately 7% of the
      control, an effect similar to that of diltiazem. In spontaneously beating
      sinoatrial (S-A) node preparations, clentiazem l0(-6)M or the higher
      concentration significantly decreased APA, V(max), and slope of slow diastolic
      depolarization, while reducing the maximum diastolic potential. The inhibitory
      effects of clentiazem showed strong suppression of APA and V(max) by 31.1 and
      47.2% of the control, respectively, whereas both clentiazem (10(-7)-10(-5)M) and
      diltiazem (10(-7)-10(-5)M) had no effects on parameters of ventricular APs. These
      results suggest that dentiazem, like diltiazem, has a preferential inhibitory
      action on cardiac slow Ca(2+) channels.

PMID- 8859930
TI  - Glyburide enhancement of lactate production in ischemic heart is modified by
      preconditioning: an in vivo experimental study in pigs by microdialysis
      technique.
AB  - The concentrations of lactate, pyruvate, and adenosine, together with some of
      their derivatives, were determined in microdialysates from 12 pig hearts, 6 of
      which were subjected to preconditioning and 40 min of ischemia (index ischemia)
      and 6 of which were subjected to only 40 min of index ischemia. Two microdialysis
      probes were inserted in ischemic myocardium. Glyburide (10 mu M) in a modified
      isotonic Krebs-Ringer phosphate buffer was administered through one of the probes
      and plain isotonic phosphate buffer was administered through the other.
      Accordingly, the experimental setup permitted us to study the metabolic effects
      of glyburide on ischemic myocardium constituting two groups that were either
      preconditioned or unpreconditioned. The preconditioning effect was validated with
      area at risk and infarction area measurements in 12 other pigs. We noted no
      functional differences between the groups. In the unpreconditioned group
      glyburide infusion resulted in enhanced 60% lactate production during index
      ischemia. However, preconditioning attenuated the enhancing effect of glyburide
      on lactate production. The interplay between the effects of glyburide and
      preconditioning on ischemic myocardium is suggested to be dependent on the
      different modes of action on the K(+)(ATP) channel.

PMID- 8859931
TI  - Direct interactions of plasminogen activators with human aortic and pulmonary
      artery endothelial cells in vitro: implications for thrombolytic therapy.
AB  - Direct interactions of plasminogen activators with arterial endothelial cells are
      important in the pathogenesis of vascular complications associated with
      thrombolytic therapy. We investigated the direct effects of various plasminogen
      activators on human aortic and pulmonary artery endothelial cell functions in
      vitro. The effects of plasminogen activators on endothelial cells were not caused
      by generation of plasmin, as shown by the absence of plasminogen and alpha(2)
      plasmin inhibitor-plasmin complex both before and after addition of plasminogen
      activators to endothelial cells. High concentrations of plasminogen activators
      increased the permeability of aortic endothelial cells to albumin. Alteplase (50
      x 10(3) IU/ml), a recombinant tissue-type plasminogen activator (t-PA), increased
      prostaglandin I(2) (PGI(2)) production by aortic endothelial cells from 175.5 +/-
      13.8 to 870.8 +/- 131.0 pg/mg cellular protein during a 2-h incubation; other
      plasminogen activators increased PGI(2) production to a lesser extent. Alteplase
      (100 x 10(3) IU/ml) also increased PGI(2) production from 152.0 +/- 16.2 to 1,080
      +/- 95.1 pg/mg cellular protein in human pulmonary artery endothelial cells. High
      concentrations of urokinases decreased the amount of endothelin-1 in the medium
      of aortic or pulmonary artery endothelial cells by as much as 93%; part of this
      decrease was attributable to degradation of endothelin-l by urokinases. Other
      plasminogen activators either had no effect on or slightly increased the
      production of endothelin-1. These changes in the function of human arterial
      endothelial cells induced by plasminogen activators may affect regional vascular
      tone, endothelial permeability, and platelet aggregability, all of which are
      important in the efficacy of thrombolysis and in the pathogenesis of such
      vascular complications as rethrombosis and hemorrhage.

PMID- 8859932
TI  - Effects of potassium channel blockers on resting tone in isolated coronary
      arteries.
AB  - The effects of several potassium channel blockers on resting vasomotor tone were
      studied in porcine isolated coronary arteries. Coronary artery rings were
      suspended in organ baths for isometric tension recording. The nonselective
      potassium channel blockers tetraethylammonium (TEA 10(-5)-3 x 10(-2) M) and 4
      aminopyridine (4-AP 10(-5)-10(-2) M) caused concentration-dependent contractions
      that were similar in rings with and without endothelium. The concentration
      response curves to TEA and 4-AP were unaffected by treatment with phentolamine (3
      x 10(-6) M),propranolol (10(-6) M), or atropine (10(-6) M). Diltiazem (10(-6) M)
      almost abolished the contractions evoked by TEA and 4-AP. Charybdotoxin (10(-9)
      10(-7) M) and apamin (10(-8)-10(-6) M), selective blockers of large and small
      calcium-activated potassium channels, respectively, and glyburide (10(-8)-10(-6)
      M), a selective blocker of ATP-sensitive potassium channels, caused little or no
      contraction in rings with or without endothelium. Therefore, in isolated coronary
      arteries, TEA and 4-AP caused contractions that were independent of the release
      of vasoactive mediators from the endothelium or perivascular nerves. These
      effects are not mediated by ATP-sensitive potassium channels or by large and
      small conductance calcium-activated potassium channels. The data are consistent
      with an effect of TEA and 4-AP on resting membrane potassium conductance in
      coronary arteries, resulting in contractions that are sensitive to inhibition by
      diltiazem. This pattern of responsiveness of isolated coronary arteries to
      potassium channel blockers differs from that observed in vessels from other
      vascular beds.

PMID- 8859933
TI  - Endothelin antagonists in salt-dependent hypertension associated with renal
      insufficiency.
AB  - Bosentan is a nonspecific antagonist for endothelin (ET) receptors, and BQ123 is
      a specific inhibitor for ET-A receptors. We compared the effects of bosentan (10
      mg/kg intravenously, i.v.) and BQ123 (10 mg/kg/h i.v.) on blood pressure and
      renal function in deoxycorticosterone acetate (DOCA)-salt rats, Dahl salt
      sensitive (Dahl-S) rats, and normotensive Wistar rats. In normotensive Wistar
      rats, bosentan and BQ123 decreased blood pressure. Only BQ123 decreased
      glomerular filtration rate (GFR) and filtration fraction. These results indicate
      that ET-A receptors play a role in glomerular function. In DOCA-salt rats,
      bosentan and BQ123 caused a decrease in blood pressure to normal range and a
      decrease in renal vascular resistances. Bosentan decreased filtration fraction.
      Paradoxically, BQ123 caused a decrease in GFR. In Dahl-S rats, bosentan and BQ123
      decreased blood pressure, but blood pressure did not reach normal ranges.
      Bosentan did not modify renal function, but BQ123 caused a decrease in the GFR
      and filtration fraction. Our results confirm the importance of specific and
      nonspecific ET antagonists in decreasing blood pressure in models of salt
      dependent hypertension. However nonspecific inhibition of ET action did not
      improve renal function and specific inhibition of ET-A receptors by BQ123
      temporarily worsened renal function.

PMID- 8859934
TI  - Effect of mibefradil on left ventricular diastolic function in patients with
      congestive heart failure.
AB  - Calcium antagonists have antihypertensive and antianginal properties. In heart
      failure, however, their use can be hazardous, as systolic function can
      deteriorate. This may not be true of the new calcium antagonist mibefradil, which
      has a new chemical structure. Calcium antagonists may also be beneficial for
      diastolic left ventricular function in coronary artery disease. To investigate
      the possible effects of mibefradil on diastolic left ventricular function, we
      performed the present study as a multicenter, double-blind,placebo-controlled,
      multiple-dose safety trial. Fifteen patients with New York Heart Association
      (NYHA) class II or III for dyspnea and depressed ejection fraction (<40%) due to
      a previous myocardial infarction were investigated. The measured nuclear
      angiographic parameters included ejection fraction (EF), peak ejection rate
      (PER), and peak filling rate (PFR). Systolic and diastolic blood pressure (SBP,
      DBP) and heart rate (HR) were also obtained. Group I (5 patients) received
      placebo medication; group IIA (6 patients) received mibefradil 6.25, 12.5, or 25
      mg/day; and group IIB (4 patients) received mibefradil 50 or 100 mg/day.
      Measurements were made before and after the first dose and after 1 week of
      treatment before and after the final dose. Mibefradil clearly decreased HR
      (repeated-measures analysis of variance p < 0.05). No statistically significant
      effects of mibefradil were noted on SBP or DBP or on systolic and diastolic left
      ventricular function. In our study conditions, mibefradil caused no worsening of
      systolic function and preserved diastolic function in short-term treatment of
      patients with decreased EF and heart failure.

PMID- 8859936
TI  - Captopril and norepinephrine-induced hypertrophy and haemodynamics in rats.
AB  - We wished to determine whether pretreatment with captopril, an angiotension
      converting enzyme (ACE) inhibitor, modified the myocardial and haemodynamic
      consequences of chronic administration of norepinephrine (NE) in rats.
      Administration of NE (0.15 mg kg(-1) h(-1) by an osmotic minipump implanted
      subcutaneously for 28 days) resulted in left but not right ventricular
      hypertrophy. Captopril (250 but not 52 mu g kg(-1) h(1) administered for 28 days)
      significantly attenuated the development of left ventricular hypertrophy (weight
      of left ventricle to body weight ratio was 0.46 +/- 0.01 0.57 +/- 0.02, 0.53 +/-
      0.02, and 0.51 +/- 0.01 for vehicle, NE, and NE plus low and high dose of
      captopril, respectively). Chronic administration of NE caused significant
      increases in systolic arterial blood pressure (BP: 194 +/- 11 vs. 130 +/- 6 mm
      Hg), systolic left ventricular pressure, heart rate (HR: 458 +/- 13 vs. 389 +/-
      15 beats/min) and dP dt(-1)(max) P(-1), an index of myocardial contractility (202
      +/- 29 vs. 91 +/- 3 s(-1)). Captopril (250 mu g kg(-1) h(-1) for 28 days)
      significantly reduced diastolic arterial BP (from 86 +/- 6 to 53 +/- 3 mm Hg).
      Concomitant administration of this dose of captopril together with NE prevented
      the NE-induced increase in systolic arterial BP but did not modify the increases
      in HR or dP dt(-1) max P(-1) (261 +/- 41 and 202 +/- 29 s(-1) in captopril and NE
      vs. NE-alone groups). Acute administration of NE (0.1-10 mu g kg(-1)
      intravenously, i.v.) produced less marked increases in cardiac contractility and
      in arterial BP in rats chronically pretreated with NE or NE plus captopril than
      in animals receiving vehicle or captopril alone. Chronic administration of NE
      and/or captopril did not significantly modify the haemodynamic effects of the
      acute administration of calcium chloride. We conclude that administration of
      captopril at 250 but not 52 mu g kg(-1) h(-1) for 28 days attenuates NE-induced
      cardiac hypertrophy and that this effect is associated with a decrease in
      systolic arterial BP. Captopril did not modify the reduced effects of acutely
      administered NE in rats treated with NE for a prolonged period.

PMID- 8859935
TI  - Differing early blood pressure and renin-angiotensin system responses to the
      first dose of angiotensin-converting enzyme inhibitors in congestive heart
      failure.
AB  - We previously demonstrated differing blood pressure (BP) responses to the first
      dose of angiotensin-converting enzyme (ACE) inhibitors in congestive heart
      failure (CHF). We wished to confirm the disparate responses to the first dose of
      these agents, study the response to repeated dosing, and explore possible
      explanations (slow, tight binding, and steric hindrance) for the phenomenon.
      Forty-eight elderly patients (aged 51-85 years) with stable CHF were studied for
      48 hours. Groups (n = 12) received one of the following: (a) perindopril 2 mg
      orally (p.o.) + placebo intravenously (i.v.) (day 1) and perindopril 2 mg p.o.
      (day 2); (b) enalapril 2.5 mg p.o. + placebo i.v. (day 1) and enalapril 2.5 mg
      p.o. (day 2); (c) placebo p.o. + perindopril at 0.167 mg i.v. (day 1) and
      perindopril 2 mg p.o. (day 2); or (d) placebo p.o. + placebo i.v. (day 1) and
      placebo p.o. (day 2). Supine BP was measured on day 1. On day 2, BP was recorded
      by ambulatory BP monitor. Blood samples were taken at baseline and at intervals
      during the 48-h study period for estimation of neurohumoral parameters.
      Inhibition of the renin-angiotensin system (RAS) was estimated by plasma ACE
      inhibition and also by the ratio of angiotensin II (Ang II)/Ang I + Ang II. On
      day I, enalapril 2.5 mg caused a greater decrease in BP than did placebo response
      between 6 and 9 h postdose. Perindopril 2 mg produced a profile of BP response
      similar to that of placebo. Ambulatory BP on day 2 was consistently lower with
      enalapril as compared with perindopril. Profiles of plasma ACE inhibition were
      similar with each active therapy. Enalapril therapy produced a greater increase
      in plasma renin activity (PRA) than did other treatments. There was no temporal
      dissociation between plasma ACE inhibition and profile of Ang peptides for any
      treatment. We have confirmed the disparate BP responses to perindopril and
      enalapril in CHF. We noted no evidence of slow, tight binding or steric hindrance
      to explain these differences.

PMID- 8859937
TI  - Mechanisms of the inotropic effects of UD-CG 212 Cl, an active metabolite of
      pimobendan, on ferret papillary muscles.
AB  - We investigated the effects of an active metabolite of pimobendan, UD-CG 212 Cl,
      on Ca(2+) transients and tension using the aequorin method. When extracellular
      [Ca(2+)] ([Ca2+]o) in the Tyrode's solution was 2 mM, UD-CG 212 C1 (10(-7)-10(
      4)M) increased the peak of Ca(2+) transients, accompanying a slight increase in
      peak tension. When [Ca(2+)]o was decreased to 0.5 mM, the twitch-potentiating
      effect of UD-CG 212 C1 was more remarkable, but the increase in the Ca(2+)
      transients at low concentrations of UD-CG 212 C1 (10(-7)-10(-6)M) was not
      significant as it was at 2 mM [Ca2+]o. The effects of UD-CG 212 Cl on the time
      courses of Ca(2+) transients and tension were evaluated at 0.5 mM [Ca2+]o. UD-CG
      212 Cl shortened the decay time of Ca(2+) transients and the time to peak
      tension. However, the relaxation time was not significantly altered. UD-CG 212 C1
      (10(-6)M) did not significantly change the relation between [Ca(2+)]i and tension
      in tetanic contraction. Therefore, the twitch-potentiating effect of UD-CG 212 Cl
      might not be due to an increase in the Ca(2+) sensitivity of the contractile
      elements. The slight increase in cyclic AMP due to the inhibition of
      phosphodiesterase type III by UD-CG 212 Cl could explain the twitch-potentiating
      effect and the faster time courses of Ca(2+) transients and tension.

PMID- 8859938
TI  - Vasoconstriction to polymorphonuclear leukocytes in the isolated, perfused rabbit
      heart: inhibition by prostacyclin mimetics.
AB  - Perfusion of the isolated rabbit heart with 5 x 10(6) human polymorphonuclear
      leukocytes (PMNL), under recirculating conditions (50 ml) and challenge with A
      23187 (0.5 mu M) increased coronary perfusion pressure (CPP) sixfold, accompanied
      by increased levels of sulfidopeptide leukotrienes (CY-SLT), which had previously
      shown to correlate linearly with the increase in CPP. Pretreatment (20 min) of
      isolated rabbit hearts with the prostacyclin (PGI(2)) analogue iloprost (3 nM)
      resulted in significant protection against the increase in CPP and in almost
      complete inhibition of 5-lipoxygenase (5-LO) product synthesis. Similarly,
      pretreatment of isolated rabbit heart with defibrotide (200 mu g/ml), a
      polydeoxyribonucleotide derivative known to inhibit PMNL activation and enhance
      PGI(2) production by heart endothelial cells, produced significant protection
      against the increase in CPP and almost complete inhibition of 5-LO product
      synthesis. Neither iloprost nor defibrotide affected the A-23187-induced
      arachidonic acid (AA) metabolism in isolated PMNL alone. Inhibition of rabbit
      cyclooxygenase by intravenous (i.v.) administration of lysine-acetylsalicylate
      (60 mg/kg) 2 h before the animals were killed significantly reduced the
      protection provided by defibrotide, with a parallel fivefold increase in
      sulfidopeptide LT levels, returning to values in the range observed in control
      hearts. Control of endogenous modulators of leukocyte-vascular wall interactions
      such as PGI(2) results in significant changes in sulfidopeptide LT production in
      an organ model of transcellular metabolism of LT A(4), suggesting a novel
      mechanism of action for cardioprotective drugs in myocardial ischemia.

PMID- 8859939
TI  - Mibefradil, a selective calcium T-channel blocker, in stroke-prone spontaneously
      hypertensive rats.
AB  - Several types of antihypertensive agents, including calcium antagonists, have
      been reported to prevent stroke and prolong survival in stroke-prone
      spontaneously hypertensive rats (SHR-SP). We investigated whether mibefradil, a
      new calcium antagonist acting selectively at the level of T-type calcium
      channels, would be able to (a) limit or prevent the structural and functional
      alterations that develop in the cerebral arteries of SHR-SP before stroke and (b)
      suppress stroke and prolong survival. Mibefradil (30 mg/kg/day) was given orally
      to young salt-loaded SHR-SP from age 5 weeks to age 20 weeks. Blood pressure (BP)
      (in conscious animals), diuresis, and proteinuria were determined weekly. After
      1012 weeks of treatment, middle cerebral arteries and aortas were removed from
      randomly selected control and treated SHR-SP. Aortic media thickness and collagen
      density were evaluated by histomorphometry. Middle cerebral arteries were mounted
      in a myograph for wall thickness determination and isometric tension recordings.
      Mibefradil completely prevented stroke and mortality, significantly limited the
      increase in BP, and opposed the increases in diuresis and proteinuria observed in
      controls. Simultaneously, mibefradil abolished vascular fibrinoid necrosis
      formation in the brain and reduced arterial thickening in the cerebral artery as
      well as in the aorta. The maximal contractile responses of the cerebral arteries
      to potassium chloride and serotonin were greater in mibefradil-treated animals
      than in controls, as were the endothelium-dependent relaxant responses.
      Mibefradil, chronically administered to young SHRSP in a dose that limits the
      development of hypertension not only prevents stroke and mortality but also
      affords protection against the vascular structural alterations which develop with
      age in these animals and preserves or improves the cerebral artery's smooth
      muscle and endothelial cell functions.

PMID- 8859940
TI  - Cardioprotective effects of NIP-121, a novel ATP-sensitive potassium channel
      opener, during ischemia and reperfusion in coronary perfused guinea pig
      myocardium.
AB  - We investigated the effect of NIP-121, a novel ATP-sensitive K+ channel opener,
      on myocardial damage during ischemia/reperfusion. The action potential and
      contractile force of coronary-perfused guinea pig right ventricular walls were
      recorded. The preparations were subjected to 30-min no-flow ischemia with or
      without NIP-121 or glibenclamide, followed by 60-min reperfusion. In untreated
      tissues, decreases in action potential duration (APD) and contractile force and
      an increase in resting tension were observed during the no-flow period. On
      reperfusion, transient arrhythmias were observed and resting or contractile force
      returned to <50% of preischemic values. NIP-121, at 0.3 microM, a concentration
      showing only a slight negative inotropic effect, caused a faster decrease in APD
      and contractile force but abolished the increase in resting tension (RT) during
      the no-flow period. On reperfusion, no arrhythmia was observed in NIP-121-treated
      preparations, and contractile force recovered to approximately 80% of the
      preischemic value. Glibenclamide 1 microM attenuated the decrease in APD but
      affected neither the decrease in contractile force nor the increase in RT during
      the no-flow period. On reperfusion, the incidence of arrhythmia was increased in
      glibenclamide-treated preparations, and the recovery of basal tension and
      contractile force was inhibited: Contractile force recovered to only
      approximately 15% of the preischemic value. NIP-121 was also shown to attenuate
      the decrease in tissue ATP during ischemia and reperfusion. We demonstrated that
      NIP-121 may have protective effects against myocardial injury during ischemia and
      reperfusion. Activation of ATP-sensitive K+ current may be an adaptive mechanism
      for cardioprotection under compromised blood flow.

PMID- 8859941
TI  - Antithrombin III prevents renal dysfunction and hypertension induced by enhanced
      intravascular coagulation in pregnant rats: pharmacological confirmation of the
      benefits of treatment with antithrombin III in preeclampsia.
AB  - We tested the hypothesis that enhanced intravascular coagulation in pregnancy
      could produce clinical symptoms similar to those of preeclampsia, such as
      hypertension, proteinuria, and edema. Having confirmed this, we then examined
      whether the pathological changes caused by intravascular coagulation could be
      suppressed by administration of antithrombin III (AT III), an endogenous
      inhibitor active to thrombin and factor X a. Intravascular coagulation was
      induced in Wistar rats on day 16-20 of pregnancy by 1-h arterial infusion of
      tissue thromboplastin (TP) through the left ventricle of the heart. One hour
      after the end of the infusion period, organ blood flows were measured by the
      radioactive ((57)Co-labeled) microsphere method, and fibrin deposition in organs
      was measured by radiolabeling with [(125)I] fibrinogen injected before TP
      infusion. Infusion of TP produced fibrin deposition in the kidney, lung, and
      liver, but not in the myometrium and placenta, as well as an 80% decrease in
      renal blood flow (RBF), with oliguria and proteinuria. TP also caused an increase
      in blood pressure (BP) accompanied by an increase in plasma renin activity (PRA),
      both of which were suppressed by bilateral nephrectomy before TP infusion. The
      prophylactic administration of AT III concentrates (60 or 300 U/kg intravenously
      (i.v.), followed by infusion of 30 or 150 U/kg/2 h, respectively) prevented all
      pathological changes in a dose-dependent manner. AT III increased placental blood
      flow regardless of the state of coagulation. These findings suggest that
      intravascular coagulation plays a significant part in the pathophysiology of
      preeclampsia and that AT III concentrates may have therapeutic potential in the
      treatment of this condition.

PMID- 8859942
TI  - Hemodynamic characterization of a novel neuropeptide Y receptor antagonist.
AB  - Defining the roles of the vasoconstrictor peptide neuropeptide Y (NPY) in the
      cardiovascular system is difficult due to lack of availability of specific NPY
      receptor antagonists. We report the in vivo NPY receptor blocking actions of a
      novel nonapeptide dimer, 1229U91 {(IleGluProDprTyrArgLeuArgTyrNH(2)(2)}, and
      describe its hemodynamic effects. In anesthetized normotensive rats, 1229U91
      produced significant and dose-dependent reductions in NPY-reduced hemodynamic
      responses. 1229U91 (3-30 nmol/kg intravenously, i.v.) attenuated the pressor
      response (34 +/- 6-84 +/- 1%) and the increases in renal vascular resistance
      (RVR, 56 +/- 9-94 +/- 2%) produced by NPY (1 nmol/kg i.v.). Intravenous
      norepinephrine (NE)-induced hemodynamic responses were not altered by 1229U91.
      1229U91 also produced dose-dependent inhibition of NPYinduced vasoconstrictor
      responses in anesthetized dogs and spontaneously hypertensive rats (SHR). These
      data demonstrate that 1229U91 is a selective NPY receptor antagonist. 1229U91 had
      no effect on resting hemodynamic variables in these preparations. In conscious
      SHR, 1229U91 did not produce significant changes in blood pressure (BP) or heart
      rate (HR) over a wide dose-range (15-1,500 nmol/kg i.v.). Lack of effect of the
      NPY receptor antagonist in SHR suggests that NPY does not contribute to the
      maintenance of BP in this hypertension model.

PMID- 8859944
TI  - Protection against reperfusion-induced arrhythmias by human thioredoxin.
AB  - Adult T-cell leukemia-derived factor (ADF), identified in the supernatant of
      adult T-cell leukemia (ATL) cell culture, is a human homologue of thioredoxin and
      consists of 104 amino acids; it has two redox-active half-cysteine residues in an
      exposed active center. Human thioredoxin has many biological activities,
      including growth promotion, cell activation, and a catalase-like radical
      scavenging activity. We examined the protective effect of human thioredoxin (h
      thioredoxin) against reperfusion-induced arrhythmias in an isolated rat heart
      model with 10-min regional ischemia followed by 30-min reperfusion. Male Wistar
      rats were assigned to six groups: a control, a superoxide dismutase (SOD 8 x
      10(4) IU/L), and a catalase group (1 x 10(6) IU/L), and three groups treated with
      h-thioredoxin [approximately .01 microM (TRX-I group), approximately 0.1 microM
      (TRX-II group), and approximately 1 microM (TRX-III group)]. In the early
      reperfusion period, h-thioredoxin reduced the incidence of ventricular
      fibrillation (VF) to 8% in the TRX-II group (p < 0.01) from the control value of
      75%. SOD and catalase reduced the incidence of VF to 43 and 33%, respectively
      (NS). During the entire reperfusion period, the incidence of VF in the SOD group
      was 79%, as compared to 83% in the control group. In the catalase and TRX-II
      groups, the incidence of VF was significantly reduced to 42 and 25%,
      respectively. These findings indicate that SOD failed to protect against the
      reperfusion-induced arrhythmias. h-Thioredoxin exerted a protective effect
      against these arrhythmias; a concentration of approximately 0.1 micro was the
      most effective.

PMID- 8859943
TI  - Myocardial metabolism during graded intraportal verapamil infusion in awake dogs.
AB  - Verapamil produces comparatively greater in vivo left ventricular (LV) depression
      than other calcium channel antagonists produce, possibly because of myocardial
      metabolic derangements in addition to L-channel antagonism. Therefore, we studied
      myocardial lipid and carbohydrate usage and the effect of insulin treatment
      during progressive verapamil toxicity. Verapamil was infused through the portal
      vein to simulate oral overdose. Eighteen mongrel dogs were instrumented to
      measure multiple hemodynamic and metabolic parameters. After 1-week recovery,
      dogs underwent control euglycemic insulin dose-response studies (n = 6) in the
      conscious state: at 1,000 mU/mm insulin infusion rate, myocardial glucose and
      lactate extraction increased seven- and threefold, respectively with no change in
      coronary artery blood flow or ventricular elasticity and end-systole (Ees). In 12
      separate dogs, intraportal graded verapamil toxicity was induced in 3 h by
      increasing the infusion rate hourly: 0.04 -- 0.08 -- 0.1 mg/kg/mm. At the end of
      hour 3, myocardial extraction of free fatty acids decreased from 33 +/- 4 to 9 +/
      3% (mean +/- SEM, p < 0.05), without significant change in myocardial blood flow
      or arterial free fatty acid concentration. Verapamil toxicity increased arterial
      glucose from 3.5 +/- 0.16 to 6.1 +/- 1.1 mM; simultaneously, myocardial glucose
      extraction doubled, although endogenous insulin concentrations did not increase.
      Arterial lactate concentrations and net myocardial lactate uptake both increased
      (p < 0.05 vs basal blue). Ees decreased from 28 +/- 1 mm Hg/mm (basal) to 20 +/-
      2 mm Hg/mm (end of hour 3, p <0.05). Animals were randomized into two treatment
      groups; either (a) insulin-glucose (1,000 mU/mm, n 6; arterial glucose was
      clamped +/- 10% with 50% dextrose), or (b) saline controls (n = 6) that received
      equivalent volume of saline. After 1-h insulin treatment, Ees increased to 34 + 3
      mm Hg; in controls, Ees was 15 +/- 3 mm Hg/mm (p < 0.05). With insulin-glucose
      treatment, neither myocardial glucose nor lactate extraction increased
      significantly (p = 0.06 for lactate). Verapamil therefore inhibits myocardial
      fatty acid uptake and impedes insulin-stimulated myocardial glucose uptake; under
      these conditions, insulin-glucose treatment increases myocardial contractile
      function independent of increased sugar transport. These findings indicate that
      verapamil toxicity produces myocardial insulin resistance and, potentially,
      nutrient deprivation that may contribute to clinically relevant negative
      inotropy.

PMID- 8859945
TI  - Endothelium-dependent relaxation by alpha 2-adrenoceptor agonists in
      spontaneously hypertensive rat aorta.
AB  - Differences in alpha(2)-adrenoceptor-induced relaxation of the aorta between
      stroke-prone spontaneously hypertensive rats (SHRSP) and control normotensive
      Wistar Kyoto rats (WKY) were studied. Changes in the tension of ring preparations
      of the aortas were measured isometrically. Relaxation was observed in the
      preparations precontracted in the presence of ONO-11113, a thromboxane A(2)
      analogue. The alpha(2)-agonist clonidine and UK-14304 induced dose-dependent
      relaxation in both the WKY and SHRSP preparations. The relaxation was impaired in
      the SHRSP preparation. A modified sandwich experiment showed that the relaxing
      substance from the SHRSP endothelium was decreased. Acetylcholine (ACh) also
      induced dose-dependent relaxation, and the relaxation was impaired in the SHRSP
      preparations. alpha(2)-Agonists induced a greater degree of impairment in the
      relaxation than did ACh. The relaxation induced by alpha(2)-agonists and by ACh
      was blocked by N G-nitro-L-arginine (L-NNA). Indomethacin improved the relaxation
      induced by ACh but not that induced by alpha(2)-agonists in the SHRSP aortas.
      These results suggest that the impairment of relaxation by alpha(2)-agonists in
      SHRSP is not caused by the increase in the release of endothelium-derived
      contracting factor (EDCF) but by the reduction in the release of nitric oxide
      (NO). Alteration of the alpha(2)-adrenoceptors and/or the intracellular mechanism
      through which NO is synthesized by stimulation of the alpha(2)-adrenoceptors may
      be the cause of the reduction in relaxation.

PMID- 8859946
TI  - Electrophysiological mechanisms for the antiarrhythmic action of (-)-caryachine
      in rat heart.
AB  - (-)-Caryachine (CNMe) is a pavine derivative, isolated from Cryptocarya chinensis
      Hemsl. We wished to illustrate the electrophysiological effect and antiarrhythmic
      potential of this compound on rat cardiac tissues. Action potential and ionic
      currents in single ventricular cells were examined by current clamp or voltage
      clamp in a whole-cell configuration. CNMe concentration-dependently suppressed
      the maximum rate of rise of the action potential upstroke (V(max)) and prolonged
      the action potential duration at 50% of repolarization (APD(50)). A voltage-clamp
      study showed that the suppression of V(max) by CNMe was associated with an
      inhibition of sodium inward current (I(Na), IC(50), O = 4.1 microM). The
      prolongation of APD(50) was associated with an inhibition of transient outward
      current (I(to), IC(50) = 16.1 microM). CNMe reduced the I(Na) with a negative
      shift of its voltage-dependent steady-state inactivation curves and slowing of
      its recovery from inactivation. The use-dependent inhibition of I(Na) by CNMe was
      enhanced at a higher stimulation rate or at a longer prepulse duration. The
      fraction of fast recovery of I(Na) was reduced, but the recovery time constant of
      fast recovery component remained unaffected. The inhibition of I(to) by CNMe (10
      30 microM) was associated with an acceleration of its time constant of
      inactivation. According to the analysis of the time course of inhibition of
      I(to), CNMe inhibited I(to) in a time-dependent manner. In isolated heart, CNMe
      could effectively inhibit ischemia/reperfusion-induced ventricular tachycardia
      with an EC(50) of 3.9 microM. The results indicate that CNMe is a strong I(Na)
      blocker with some I(to) blocking activity. The inhibition of I(Na), and I(to) may
      contribute to its antiarrhythmic activity against ischemia/reperfusion
      arrhythmia.

PMID- 8859947
TI  - Effect of aging on arteriolar dilatation induced by prostaglandin E(1)
      incorporated in lipid microspheres.
AB  - To investigate the effect of aging on vasodilation of arterioles induced by
      prostaglandin E1 incorporated in lipid microspheres (lipo-PGE(1)), we measured
      the diameter of the anterior ciliary artery in patients aged <65 years (young
      group) and in patients aged >65 years (elderly group). An eyelid retractor was
      affixed to the right eyelid while patients were under general anesthesia, and
      changes in the diameter of the arteriole were continuously monitored by surgical
      stereomicroscopy for 10 min after the intravenous (i.v.) injection of lipo-PGE(1)
      (0.2 mu g/kg). We also measured mean arterial pressure (MAP) and heart rate (HR)
      during the study. The diameter of the arteriole in the young group began to
      increase significantly 1 min after the injection (p < 0.01), reaching the maximal
      increase (42.3 +/- 7.4% above the preinjection level) at 3 min after continuous
      dilatation at the end of the study. In the elderly group, the diameter began to
      increase 2 min after the injection (p <0.01), reached the maximal value (33.2 +/-
      12.7% above the preinjection level) at 5 min, and then gradually decreased to the
      baseline value. MAP decreased continuously after the injection in both groups;
      there was no significant difference between the groups. HR in the young group
      began to increase after the injection and then returned to the baseline level,
      but in the elderly group it showed continuous increase throughout the study.
      These results suggest that aging impaired the vasodilatory response to lipo
      PGE(1) in the anterior ciliary artery.

PMID- 8859948
TI  - Therapeutic effects of nitric oxide-donor isosorbide dinitrate on atherosclerosis
      induced alterations in hemodynamics and arterial viscoelasticity are independent
      of the wall elastic component.
AB  - Whether the arterial elastic structures are involved in the beneficial effects of
      long-term treatment with organic nitrates on atherosclerosis-induced changes in
      hemodynamics and arterial wall viscoelastic properties, are case for angiotensin
      converting enzyme (ACE) inhibitors, is not known. In the present study,
      atherogenic (A) diet, and isosorbide dinitrate (ISDN) (I) (60 mg Risordan LP,
      daily dose) were given concomitantly for 4 months to adult Pitman-Moore minipigs
      (A + I animals, n = 8), which were compared with A (n = 8) or control (C, n = 8)
      animals. Blood flow was investigated by hemodynamics in the hindlimb arterial
      bed; and wall rheology, histomorphometry and elastin; and desmosine (DES) and
      isodesmosine (IDE) contents in the abdominal aorta. Atherosclerosis prominently
      impaired the function of capacitance and resistance arteries, altered blood
      pressure contours, increased aortic stiffness and wall tension, and reduced
      parietal viscoelasticity through viscous component blunting. The treatment with
      ISDN significantly improved aortic pulsatility, arteriolar opposition to blood
      flow, and blood pressure (BP) contours by restoring, at least in part, the wall
      viscoelastic properties. However, there was no significant change in the area of
      the pressure-diameter curve hysteresis between the three animal groups. In
      contrast, ISDN reduced neither the cross-sectional area of lesions nor the losses
      in wall elastin content and had no influence on lipid accumulations in vessels
      and in the blood. The present results demonstrate that the beneficial hemodynamic
      and wall viscoelastic effects elicited by ISDN in atherosclerotic minipigs are
      not accounted for by therapeutic properties of the nitric oxide (NO) donor
      against alterations of elastic structures, but by the viscoelastic properties in
      the arterial wall.

PMID- 8859949
TI  - Genetic admixture in the late pleistocene.
AB  - The replacement hypothesis of modern human origins holds that the original
      population of modern humans expanded throughout the world, replacing existing
      archaic populations as it went. If this expanding population interbred with the
      peoples it replaced, then some archaic mitochondria might have been introduced
      into the early modern gene pool. Such mitochondria would be recognizable today
      because they should differ from other modern mitochondria at several times the
      number of sites that we are used to seeing in pairwise comparisons. In this paper
      we ask what can be inferred from the absence of these "divergent" mitochondria
      from modern samples. We show that if the effective number of females in our
      species has been large for the past 40,000 years, then the level of admixture
      must have been low. For example, if this effective number exceeded 1.6 million,
      then we can reject the hypothesis that more more than 2/1,000 of the mitochondria
      in the early modern population derived from admixture with archaic peoples. We
      argue elsewhere that regional continuity would be detectable in the fossil record
      only if the rate of admixture exceeded 76%. Here, we show that this level of
      admixture would require the effective female size of the human population to have
      been less than 1,777 for the past 40,000 years.

PMID- 8859950
TI  - Seasonal and sex variation in physical activity levels among agro-pastoralists in
      Nepal.
AB  - Considerable attention has been devoted to variation in levels of energy
      expenditure between and within populations; these are commonly evaluated
      following international guidelines for grading light, moderate, and heavy
      physical activity levels (PAL). This study presents activity profiles by season
      and sex for subsistence agro-pastoralists in Nepal, comparing data for a sample
      of 20 men observed four times across the year with previously published data on
      women. Total energy expenditure (TEE) was estimated from direct minute-by-minute
      observation (totaling 1,679 h for men, 3,601 h for women) and measures of the
      energy cost of single tasks (117 for men, 168 for women). PAL were calculated and
      graded as multiples of predicted basal metabolic rate (BMR). Despite an
      explicitly egalitarian organization of labor, men achieved higher PAL than women
      (P <.0001), although according to international gradings, both men and women
      assume moderately heavy PAL in the winter and very heavy PAL in the monsoon. PAL
      were 1.88 and 2.22 x BMR for men in respective seasons (P <.005; TEE, 11.8 MJ/d
      and 13.9 MJ/d) and 1.77 and 2.0 x BMR for women (TEE, 9.1 MJ/d and 10.5 MJ/ d).
      High TEE values result from time-consuming work in subsistence tasks, most of
      which are of moderate energy cost. Results show that the international guideline
      (FAO/WHO/UNU [1985]) for grading levels of energy expenditure, which adopts
      discrepant sex-specific values to define thresholds for moderate or heavy PAL,
      can mask significant gender variation. Male/female ratios of PAL values are
      suggested instead for population-level comparisons.

PMID- 8859951
TI  - Stable carbon and nitrogen isotopic composition of diet and hair of Gidra
      speaking Papuans.
AB  - The carbon and nitrogen stable isotopic composition of the scalp hair and diet of
      Gidra-speaking people in four villages in Papua New Guinea is presented. The
      isotopic composition of hair was measured, while that of the diet was estimated
      from food consumption survey data and the measured isotopic composition and
      protein and carbohydrate contents of food items. The average isotopic ratios of
      the hair samples and of the diet varied among the four study villages, which were
      selected because of their diverse ecological settings. Comparison was made
      between hair and calculated dietary isotopic compositions. Two of the four diet
      hair enrichment values obtained for 13C (+1.8 and 2.2%) were similar to those
      previously reported (1.4-2.0%), but the other two values (3.7 and 4.8%) were
      greater than in earlier reports. 15N enrichment was systematically greater (by
      1.0%) than reported values (4.3%) except for one village, where a much greater
      enrichment (6.9%) was found. The factors potentially relevant to these deviations
      are discussed. Possible errors in estimating the dietary isotopic composition and
      minor modifications of dietary habits revealed by food consumption surveys could
      explain most of the discrepancies. However, the great enrichment of 15N found in
      one of the villages remains unexplained.

PMID- 8859952
TI  - Dermatoglyphic variation in Europe.
AB  - We describe the geographic variation patterns of 236 dermatoglyphic variables
      (118 for each sex) for 74 samples in Europe. Using principal components analysis
      and rotating to simple structure, we simplified these patterns to the first 20
      axes, representing 74.2% of covariation. We then used heterogeneity tests,
      interpolated surfaces, one-dimensional and directional correlograms, and
      distances between correlograms to analyze the factor scores of these 20 axes. We
      also ordinated the 74 localities. The data are remarkable for showing little
      spatial autocorrelation, despite significant heterogeneity among localities. Only
      three factor axes exhibit consistently significant correlograms, indicating that
      there are few spatial patterns in the original variables in Europe. Almost all
      correlations between pairs of variables occur within serially homologous
      character sets and are thus developmentally determined. There is some support for
      demic diffusion from the southeast in finger patterns and ridge counts. We
      compare these results to those of previous studies and note that Lapps and
      Icelanders are outliers with respect to both genetics and finger tip variables,
      whereas Tatars are outliers with respect to craniometrics and dermatoglyphics.

PMID- 8859953
TI  - Possible paleopathological evidence of treponematosis from a megalithic site at
      Agripalle, India.
AB  - An Iron Age (megalithic) skull recovered from a cist burial complex at Agripalle,
      Andhra Pradesh, India, exhibits extensive erosion of the calvarium, areas of
      sclerotic diploe, irregular osteitic and periosteitic lesions, and deep
      ulcerations with a granulomatous appearance of nodular foci due to bone
      remodeling. These lesions are found over the entire surface, but are less severe
      in the temporal region and in the occipital region below lambda. There is
      extensive ulceration and destruction of the orbital roof and the nasopalatine
      region. A thick bony mass representing a healed lesion is present on the nasal
      margin. Comparison with the pathologic skeletal series of Ortner and Putschar
      ([1981] Smithson. Contrib. Anthropol. 28:180-218), Steinbock ([1976]
      Paleopathology: Diagnosis and Interpretation, pp.86-169), and Calvin ([1964]
      Bones and Disease: Evidence of Disease and Abnormality in Early Man) indicates
      that these findings warrant a diagnosis of an advanced stage of treponematosis.
      The material from Agripalle, together with similar specimens recovered from the
      sites of Bhimbetka (Iron Age) and Inamgaon (Chalcolithic), furnish additional
      evidence supporting the hypothesis of the prehistoric antiquity of treponemal
      disease in both the New and Old Worlds.

PMID- 8859954
TI  - Reproduction in free-ranging Propithecus verreauxi: estrus and the relationship
      between multiple partner matings and fertilization.
AB  - Female sifaka mate selectively with one or more resident and/or non-resident
      males during the breeding season. Various adaptive explanations have been
      advanced to explain why female primates mate with multiple males including that
      1) females seek to confuse paternity and thereby forestall male infanticide
      and/or ensure male infant care or 2) females seek to ensure fertilization.
      Assessing the power of fertilization insurance to explain mating patterns in
      females requires information on the temporal relationship between mating and
      ovarian hormones. The hormonal correlates of reproduction and mating in free
      ranging Propithecus verreauxi were investigated using excreted steroids as
      indices of reproductive state. Solid-phase extraction and radioimmunoassay
      techniques were used to measure unconjugated estradiol (E(2)) and progesterone
      (P(4)) in 485 desiccated fecal samples collected from five female sifaka before
      and during the breeding season at Beza Mahafaly, Madagascar. Results suggest that
      behavioral estrus was characterized by 10 to 15-day elevations in E(2); hormonal
      activity was observed to be similar to pseudo-estrus reported for other lemur
      species; apparent conception was associated with sustained P4 elevations
      beginning 1 to 3 days post-estrus with gestational phase elevations of E2
      beginning 42 to 45 days post-conception; and mating with multiple partners
      appeared not to be a prerequisite to fertilization, as conception resulted from
      both monoandrous and polyandrous matings. These preliminary data suggest that
      fertilization insurance is not adequate to explain polyandrous mating in sifaka
      at Beza Mahafaly.

PMID- 8859955
TI  - Movement of the epiglottis in mammals.
AB  - In contrast to adult humans, the epiglottis of other mammals and infant humans is
      situated close to the soft palate. It has been argued that this posture is
      maintained during swallowing, with food passing laterally around an intact
      airway. To test this supposition, the movement of the epiglottis in two
      contrasting mammalian species, pigs and ferrets, was studied by placing
      radiopaque markers on the epiglottis and soft palate. Swallowing was observed
      with videofluoroscopy while the animals were feeding on hard and soft foods,
      liquids, and food mixed with barium sulfate. Analysis of the images showed that
      bolus formation and downward movement of the epiglottis away from the soft palate
      were unvarying phenomena in both animals for all tested foods. The duration of
      the epiglottic movement was approximately 0.3 S for liquids and slightly longer
      for solids. Because swallowing never occurred past an upright epiglottis, the
      results of this study do not support the hypothesis that adult animals maintain a
      patent airway during swallowing. Instead, the epiglottis in nonhuman mammals
      downfolds similarly to that of adult humans during swallowing.

PMID- 8859956
TI  - Regression equations for estimating stature from long bones of early holocene
      European samples.
AB  - Regression equations for estimating living stature from long bone lengths have
      been calibrated on a sample of European Neolithic skeletons (33 males and 27
      females) by using both least-squares (model I) and major axis (model II)
      regression techniques. Stature estimates of the skeletal sample have been made by
      means of Fully's anatomical method, a procedure based on the sum of all osseous
      components of height, providing the best approximations to the actual stature.
      The calculated equations have been tested, along with those generally used to
      predict stature of earlier European remains, on a small, well-preserved sample
      including Late Upper Paleolithic, Mesolithic, and Neolithic skeletons. The
      results indicate that the model II equations are particularly useful when very
      short or very tall individuals are involved and, at the same time, are among the
      best predictors of stature in less extreme conditions.

PMID- 8859957
TI  - Sexual dimorphism in the pelvic midplane and its relationship to Neandertal
      reproductive patterns.
AB  - The fragmentary nature of the fossil record has limited the analysis of the
      Neandertal pelvis to the superior pubic ramus and the pelvic inlet. From an
      obstetric viewpoint, the pelvic midplane or "plane of least dimensions," defined
      by the distance between the ischial spines, must be considered in the analysis of
      hominid reproduction. We examined the relationship between BSD and weight in a
      mixed sex hospital population undergoing diagnostic computed tomography (CT)
      scans (41 females and 40 males). Because femoral head diameter squared (FH(2))
      has been used as a proxy for weight in skeletal populations, it was also analyzed
      with respect to BSD and weight. Bivariate regression analysis of BSD with other
      body dimensions indicates the presence of significant sex differences. In
      females, but not in males, weight is a statistically significant predictor of
      BSD. FH(2) is an even better predictor of BSD in females while nonsignificant in
      males. Although weight and FH(2) are significantly correlated with BSD in
      females, FH(2) does not predict weight in females as well as it does in males.
      The positive correlation between skeletal frame size and BSD in females is
      indicative of an evolutionary pattern that must take into account the pressures
      of reproduction. Our results indicate that critical dimensions of the pelvis must
      increase as the maternal skeleton becomes larger. These results provide a context
      for the interpretation of the reproductive patterns of a relatively robust
      hominid population like the Neandertals.

PMID- 8859958
TI  - Preliminary examination of non-occlusal dental microwear in anthropoids:
      implications for the study of fossil primates.
AB  - Most studies of microscopic wear on non-human primate teeth have focused on the
      occlusal surfaces of molars. Recent analyses of the buccal surfaces of human
      cheek teeth have demonstrated an association between diet and dental microwear on
      the these surfaces as well. In the current study, we examine microwear on both
      the buccal and lingual surfaces of non-human primate molars to assess the
      potential of these surfaces to reveal information concerning anthropoid feeding
      behaviors. We compare frequency of microwear occurrence in 12 extant and 11
      fossil anthropoid species. Among the living primates, the occurrence of microwear
      on nonocclusal surfaces appears to relate to both diet and degree of
      terrestriality. The implications of this research for the inference of feeding
      behaviors and substrate use in fossil cercopithecoids are discussed.

PMID- 8859959
TI  - New pedal remains of Megaladapis and their functional significance.
AB  - New remains of Megaladapis from the caves within the Ankarana Range of northern
      Madagascar and the cave site of Ankilitelo near Toliara in southwestern
      Madagascar add considerably to the present sample of pedal remains for this
      genus. Here we describe and analyze the new pedal material and discuss the
      function of the Megaladapis foot in terms of positional behavior and substrate
      use. The northern specimens belong to the M. madagascariensis /M. grandidieri
      group in terms of size and morphology whereas the new southwestern fossils are
      assigned to M. madagascariensis. The new specimens demonstrate that the small and
      intermediate sized M. madagascariensis and M. grandidieri were very similar in
      anatomy and inferred locomotor function, findings that also support the prior
      suggestion that they belong to a single widespread subgenus (Megaladapis). The
      new fossils provide the first examples of many pedal elements and present the
      first opportunity to analyze the whole pedal complex from associated remains. The
      foot of Megaladapis is distinctive among primates in numerous features. Intrinsic
      proportions of the hindlimb indicate that the foot is relatively longer than that
      of any other primate. The first complete calcanei reveal a large and highly
      modified hindfoot. The calcaneus is reduced distally, indicating an emphasis on
      climbing over leaping or quadrupedal walking and running. Proximally, a large,
      medially directed calcaneal tuberosity suggests both a strong inversion component
      to plantarflexion and a well-developed abductor mechanism and recalls the
      calcaneal morphology of the larger lorisines in some respects. Talar shape is
      consistent with considerable tibial rotation during plantarflexion and
      dorsiflexion. The subtalar joint is designed to emphasize supination/pronation
      and medial/lateral rotation over proximodistal translation. The distal tarsals
      are extremely reduced in length, and they form a high transverse arch and a
      serial tarsus; this configuration promotes inversion/eversion at the transverse
      tarsal joint. The phalanges are long and moderately curved, and the hallux is
      very long, robust, and abducted. Pedal morphology suggests that Megaladapis
      (subgenus Megaladapis) was well adapted to exploit an arboreal
      environment.(ABSTRACT TRUNCATED)

PMID- 8859960
TI  - Brief communication: a test and correction of the clavicle method of Stout and
      Paine for histological age estimation of skeletal remains.
AB  - The histological method developed by Stout and Paine ([1992] Aln. J. Phys.
      Antropol. 87:111-115) for estimating age at death using the clavicle is tested on
      a known age independent sample from a nineteenth century cemetery near
      Spitalfriedhof St. Johann in Basel, Switzerland. The mean absolute difference
      between reported ages and histologically predicted ages is 5.5 years. Mean
      predicted age for the sample is different from mean reported age. This difference
      is accounted for by differences in the age distributions between the original
      autopsy sample used to derive the histological age-predicting formula and the
      cemetery sample, and an inherent loss of reliability of histological age
      predictions for the skeletal remains of older individuals. A new formula based
      upon the combined original autopsy sample of Stout and Paine (1992) and the Swiss
      cemetery sample is presented. It is recommended that this formula be used when
      estimating ages for older individuals or archaeological skeletal samples.

PMID- 8859961
TI  - Brief communication: diet-induced changes in rates of human tooth microwear: a
      case study involving stone-ground maize.

PMID- 8859998
TI  - Towards meeting the Paracelsus Challenge: The design, synthesis, and
      characterization of paracelsin-43, an alpha-helical protein with over 50%
      sequence identity to an all-beta protein.
AB  - In response to the Paracelsus Challenge (Rose and Creamer, Proteins, 19:1-3,
      1994), we present here the design, synthesis, and characterization of a helical
      protein, whose sequence is 50% identical to that of an all-beta protein. The new
      sequence was derived by applying an inverse protein folding approach, in which
      the sequence was optimized to "fit" the new helical structure, but constrained to
      retain 50% of the original amino acid residues. The program utilizes a genetic
      algorithm to optimize the sequence, together with empirical potentials of mean
      force to evaluate the sequence-structure compatibility. Although the designed
      sequence has little ordered (secondary) structure in water, circular dichroism
      and nuclear magnetic resonance data show clear evidence for significant helical
      content in water/ethylene glycol and in water/methanol mixtures at low
      temperatures, as well as melting behavior indicative of cooperative folding. We
      believe that this represents a significant step toward meeting the Paracelsus
      Challenge.

PMID- 8859999
TI  - Crystallization and preliminary x-ray crystallographic studies of ketosteroid
      isomerase from Pseudomonas putida biotype B.
AB  - The delta(5)-3-ketosteroid isomerase from Pseudomonas putida biotype B has been
      crystallized. The crystals belong to the space group P2(1)2(1)2(1) with unit cell
      dimensions of a = 36.48 angstrom, b = 74.30 angstrom, c = 96.02 angstrom, and
      contain one homodimer per asymmetric unit. Native diffraction data to 2.19
      Angstrom resolution have been obtained from one crystal at room temperature
      indicating that the crystals are quite suitable for structure determination by
      multiple isomorphous replacement.

PMID- 8860000
TI  - Purification, crystallization, and preliminary x-ray diffraction studies of tRNA
      guanine transglycosylase from Zymomonas mobilis.
AB  - The tRNA modifying enzyme tRNA-gnanine transglycosylase (Tgt) catalyzes the
      exchange of guanine in the first position of the anticodon with the quenine
      precursor 7-aminomethyl-7-deazagnanine. Tgt from Zymomonas mobilis has been
      purified by crystallization and further recrystallized to obtain single crystals
      suitable for X-ray diffraction studies. Crystals were grown by vapor
      diffusion/gel crystallization methods using PEG 8,000 as precipitant.
      Macroseeding techniques were employed to produce large single crystals. The
      crystals of Tgt belong to the monoclinic space group C2 with cell constants a =
      92.1 A, b = 65.1 A, c = 71.9 A, and beta = 97.5 degrees and contain one molecule
      per asymmetric unit. A complete diffraction data set from one native crystal has
      been obtained at 1.85 A resolution.

PMID- 8860001
TI  - Crystallization and preliminary x-ray crystallographic studies of L-2-haloacid
      dehalogenase from Pseudomonas sp. YL.
AB  - The dimeric L-2-haloacid dehalogenase from Pseudomonas sp. YL, (subunit mass,
      26179 Da), has been crystallized by vapor diffusion, supplemented by repetitive
      seeding, against a 50 mM potassium dihydrogenphosphate solution (pH 4.5)
      containing 15% (w/v) polyethylene glycol 8,000 and 1% (v/v) n-propanol. The
      crystals belong to the monoclinic space group C2 with unit cell dimensions of a =
      92.21 angstrom, b = 62.78 angstrom, c = 50.84 angstrom, and beta = 122.4 degrees,
      and contain two dehalogenase dimers in the unit cell. They are of good quality
      and diffract up to 1.5 angstrom resolution.

PMID- 8860002
TI  - Characterization of crystals of Penicillium purpurogenum acetyl xylan esterase
      from high-resolution x-ray diffraction.
AB  - Acetyl xylan esterase from Penicillium purpurogenum, a single-chain 23 kDa member
      of a newly characterized family of esterases that cleaves side chain ester
      linkages in xylan, has been crystallized. The crystals diffract to better than 1
      A resolution at the Cornell High Energy Synchrotron Source (CHESS) and are highly
      stable in the synchrotron radiation. The space group is P2(1)2(1)2(1) and cell
      dimensions are a = 34.9 A, b = 61.0 A, C = 72.5 A.

PMID- 8860003
TI  - Crystallization and preliminary x-ray diffraction study of 1 ,3,8
      trihydroxynaphthalene reductase from Magnaporthe grisea.
AB  - 1,3,8-Trihydroxynaphthalene reductase was crystallized in the presence of NADPH
      and the inhibitor tricyclazole. The crystals are trigonal, space group P3(1)21 or
      its enantiomorph P3(2)21. Two crystal forms with slightly different cell
      dimensions were obtained. Form A has unit cell dimensions a = b = 142.6 angstrom,
      c = 70.1 angstrom and form B cell dimensions a = b = 142.6 angstrom, c = 72.9
      angstrom. The diffraction pattern of the latter crystal form extends to 2.5
      angstrom resolution.

PMID- 8860004
TI  - Distribution of composite CYP1A1 genotypes in Africans, African-Americans and
      Caucasians.
AB  - We present the genotype distribution of the CYP1A1 gene in a sample of over 300
      subjects of various ethnic origins. Genotypes are presented as composites of
      eight possible alleles, taking into account the three major polymorphisms,
      including a recently described African-American-specific MspI RFLP. A new
      nomenclature system is presented for clarifying the various haplotypes.
      Interesting interracial differences in allelic frequencies and admixture rates
      were observed for the three polymorphisms. Because of the importance of the
      CYP1A1 gene (which encodes the aromatic hydrocarbon hydroxylase) as a biomarker
      of genetic susceptibility to environmental carcinogens such as polycyclic
      aromatic hydrocarbons, these data may provide a useful reference for future
      studies of relationships between CYP1A1 genotype and disease susceptibility.

PMID- 8860005
TI  - Phenylketonuria in Costa Rica: preliminary spectrum of PAH mutations and their
      associations with highly polymorphic haplotypes.
AB  - A preliminary evaluation of the molecular basis of phenylketonuria (PKU) in Costa
      Rica was made by performing mutational analyses in the six PKU families
      identified to date. These studies revealed the presence of the previously
      reported European mutations IVS1nt5, L48S, E221G and IVS12ntl as well as the
      novel mutation IVS7nt3. The combined use of the STR, VNTR and XmnI polymorphic
      systems for the PAH gene resulted in a discriminant distribution of haplotypes
      among normal and mutant chromosomes and suggests its potential usefulness for
      future diagnostic applications in Costa Rican PKU kindreds. This is the first
      report of a genetic analysis in a Central American PKU population.

PMID- 8860006
TI  - Coagulation factor XIIIA subtypes in Brazilian Indians.
AB  - A total of 340 individuals living in seven localities of two Brazilian Indian
      groups (Macushi and Icana River Indians) were studied with respect to coagulation
      factor XIIIA subtypes. No inter- or intra-tribal differences were observed. The
      most striking finding was that FXIII*1A, an allele which is fairly common among
      Asiatic Mongoloids like the Japanese (27%), was nearly absent in these Indians.

PMID- 8860007
TI  - Molecular characterization of erythrocyte glucose-6-phosphate dehydrogenase
      deficiency in Al-Ain District, United Arab Emirates.
AB  - In a cross-sectional study, the activity, electrophoretic mobility and genotypes
      of glucose-6-phosphate dehydrogenase (G6PD) were determined among healthy, UAE
      national school boys from Al-Ain District in the United Arab Emirates, The
      prevalence of G6PD deficiency in this population sample was 11%. The majority of
      G6PD-deficient subjects were descendants of Omani, Baluchi or Yemeni migrants. Of
      18 deficient subjects, 16 had an enzyme activity of < 10% of normal while 2 had
      an activity of just above 10%. Electrophoresis was performed on 166 samples and
      showed that, apart from deficient samples, all had the normal mobility of G6PD
      type B. Of the 18 deficient subjects, 14 had the B type mobility of G6PD
      Mediterranean and 4 had the A type mobility of G6PD A-. Genotyping demonstrated
      that 10 had the Mediterranean mutation while 3 had the A- mutation, consistent
      with their electrophoretic mobility. Another 3 had the G6PD Aures mutation,
      recently described as polymorphic in Algeria and Spain. The mutations in the
      remaining 2 subjects have not yet been identified.

PMID- 8860008
TI  - Butyrylcholinesterase variants (BCHE and CHE2 Loci) associated with erythrocyte
      acetylcholinesterase inhibition in farmers exposed to pesticides.
AB  - Farmers exposed to pesticides and classified as mildly poisoned and controls on
      the basis of erythrocyte acetylcholinesterase (AChE) activity were examined for
      butyrylcholinesterase (BChE) genetic variability. The mildly poisoned group
      showed a significantly higher frequency of non-usual phenotypes (13.1%) than the
      control group (1.7%). These phenotypes showed a relative risk (RR) of 8.8 of
      erythrocyte AChE inhibition when compared to the usual phenotype. Among the
      subjects with the usual phenotype, the CHF2 C5- phenotype was more frequent in
      the mildly poisoned group (94.3%) than in the control group (81.0%), leading to
      an RR of 3.9 when compared to the CHE2 C5+ phenotype. When the total sample was
      classified into two groups (usual CHE2 C5+ and other phenotypes), the usual CHE2
      C5+ phenotype was found to be responsible for a preventive fraction of about 14%
      of the cases of mild poisoning. The present data suggest that BChE genetic
      variability offers differential protection against erythrocyte AChE inhibition.

PMID- 8860009
TI  - The codon 31 polymorphism of the p53-inducible gene p21 shows distinct
      differences between major ethnic groups.
AB  - The codon 31 polymorphism of the p53-inducible protein p21 was studied with
      respect to allele frequency variations between some major ethnic groups. The
      frequency of the Al (Arg) allele showed highly significant variations ranging
      from 4% in Caucasians (Swedes) to 50% in Chinese. Compared to Caucasians, a
      relatively high frequency was found in African Blacks (29%) and Indians (16%).
      Furthermore, Finns and Mordvinians also had higher frequencies (9-10%) than west
      Europeans (French and Swedes), consistent with an Asiatic Mongoloid influence
      known to exist in Finno-Ugrian tribes. The geographic allele frequency patterns
      of p53 and its effector protein p21 were quite different. The p21 A1 mutations in
      African, Asiatic and European populations were identical at the DNA level. The
      geographical distribution of the A1 allele suggests an independent origin in
      Africa and Asia. The very pronounced ethnic differentiation of tumour suppressor
      genes and the fact that tumour suppressor genes may be teratogenes suggest that
      these polymorphisms are maintained by natural selection, probably operating in
      the intrauterine period.

PMID- 8860010
TI  - Sharing at the major histocompatibility complex affects the secondary sex ratio
      in differing ways.
AB  - We analysed the effect of HLA loci on the secondary sex ratio, and investigated
      whether allele sharing between parents and between mother and child, or child
      homozygosity, affected the viability of male embryos, which are generally less
      resistant to unfavourable conditions during pregnancy. The sharing conditions at
      the B and DR loci showed significantly differing effects: HLA-B seemed to favour
      female births, while, in pregnancies subsequent to the first, HLA-DR seemed to
      favour male births. Both HLA-B and DR loci seemed to work through immunological
      mechanisms.

PMID- 8860011
TI  - 2176insC: a novel mutation in exon 13 of the cystic fibrosis gene.

PMID- 8860012
TI  - A splicing mutation in intron 16 of the cystic fibrosis transmembrane conductance
      regulator gene, associated with severe disease, is common on Reunion Island.
AB  - In addition to the frequent delta F508 and Y122X mutations on cystic fibrosis
      (CF) chromosomes of patients from Reunion Island, one splicing mutation, 3120+1G-
      >A is observed relatively frequently (12.5%) in this group, in comparison with
      the French metropolitan population (<0.001 %). This mutation, disrupting the 5'
      splice donor site of intron 16, can be detected easily by restriction enzyme
      BstNI digestion. In 2 CF patients homozygous for this mutation, the clinical
      pattern was severe, with both pancreatic insufficiency and respiratory symptoms.

PMID- 8860013
TI  - Molecular characterization of G6PD deficiency in Oman.
AB  - Screening of unselected university students in the Sultanate of Oman revealed an
      overall frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency of 26%
      in males. Samples from 23 G6PD-deficient individuals (a random sub-sample of the
      student population), were characterised biochemically and at the molecular level.
      Of 20 deficient men, 15 had G6PD Mediterranean, 2 had G6PD Chatham, 1 had G6PD A-
      and in 2 the mutation is not yet known. Of the 3 G6PD-deficient woman, 2 were
      homozygous for the G6PD Mediterranean mutation and 1 was a genetic compound, G6PD
      Mediterranean/G6PD A- (the first report of this genotype). Our findings establish
      that the G6PD Mediterranean mutation accounts for most cases of G6PD deficiency
      in Oman. The presence of G6PD A- at a polymorphic frequency can be regarded as
      evidence of significant gene flow from Africa.

PMID- 8860014
TI  - Detection of four novel mutations in the porphobilinogen deaminase gene in French
      Caucasian patients with acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is an autosomal dominant disorder
      characterized by alterations of the gene encoding porphobilinogen deaminase
      (PBGD: EC 4.3.1.8), the third enzyme of the heme biosynthetic pathway. The
      molecular heterogeneity of the mutations causing AlP has been demonstrated with a
      reported predominance of single base substitutions resulting in amino acid
      changes. The molecular basis of AIP in four French patients was investigated
      using denaturing gradient gel electrophoresis followed by direct sequencing. We
      describe four different novel mutations that affected exon 12 (a frameshift and
      an exon skipping), exon 4 (a stop codon) and exon 15 (a frameshift inducing a
      stop codon). This study further documents the molecular heterogeneity of
      mutations in the PBGD gene in the French Caucasian population and reports types
      of mutations relatively uncommon in AIP.

PMID- 8860026
TI  - Five-year incidence rates and intraoral distribution of root caries among
      community-dwelling older adults.
AB  - The 5-year incidence and intraoral distribution of decayed and filled root
      surfaces were evaluated in 379 black and 323 white residents of North Carolina
      aged 65 and older. During the period of study, approximately 39% of blacks
      developed at least one root DFS compared with 52% for whites (Wald X(2) test, p =
      0.062). When the results were calculated using the net root DFS increment, blacks
      did not have significantly higher rates than whites over the 5-year study period
      (0.52 surfaces/person versus 0.42 surfaces/person, Survey Regression, n = 363, p
      = 0.708). However, for blacks, the 5-year incidence density rate of root DFS was
      0.26 per 60 surface-months at risk, and for whites the rate was 0.19 new root DFS
      per 60 surface-months (incidence density ratio = 1.33, 95% CI = 1.01-1.76, p =
      0.047). Intraoral distribution patterns for root caries incidence revealed that
      the approximal surfaces of the anterior teeth were involved most frequently,
      particularly in the mandible and maxilla in whites, followed in decreasing order
      by the buccal surfaces of the lower anteriors and the mesial surfaces of the
      upper anteriors in blacks. Although root caries incidence rates were obviously
      low, there were significant differences in the occurrence of caries between
      blacks and whites. The pattern of occurrence was similar for both races with root
      surface disease being concentrated in the approximal surfaces of the anterior
      teeth in a small proportion of affected individuals, with whites presenting more
      filled root increments than blacks. These findings suggest a need for more caries
      treatment in blacks and increased monitoring of this population since they are at
      a higher risk for root caries.

PMID- 8860027
TI  - Properties of whole saliva and dental plaque in relation to 40-month consumption
      of chewing gums containing xylitol, sorbitol of sucrose.
AB  - Samples of whole saliva and dental plaque were collected from initially 10-year
      old subjects who participated in a 40-month cohort study investigating the effect
      of chewing gum usage on caries rates. The subjects represented nine cohorts of
      which one did not receive gum, while in eight cohorts the subjects received gum
      containing either xylitol, sorbitol, their mixtures, or sucrose as bulk
      sweeteners, the maximum sweetener consumption in the form of gums being up to
      10.7 g/day, used in 3-5 daily chewing episodes. Gum usage had no significant
      effect on the levels of salivary protein, IgA, alpha-amylase, peroxidase,
      lysozyme, SCN and buffer capacity. At the endpoint, the group that received 100%
      xylitol pellet-shaped gum five times/day, had significantly lower levels of
      sucrase (p <0.05) and free sialic acid (p < 0.001) in whole saliva than at
      baseline. This group showed significantly (p <0.05) smaller plaque index scores
      at two cross-sectional measurements, and exhibited the lowest log(10) counts of
      salivary lactobacilli at endpoint than most other groups. The salivary levels of
      peptidase(s) (oligopeptidase B-like enzymes) hydrolyzing N-alpha-benzoyl-DL
      arginyl-p-nitroaniline were significantly (p<0.05) or almost significantly lower
      in groups which received 100% xylitol pellet gums. All groups exhibited obviously
      an aging-related increase of salivary mutans streptococcus scores, except the
      above xylitol group in which the mean scores did not change.

PMID- 8860028
TI  - Grey discoloration for the diagnosis of secondary caries in teeth with class II
      amalgam restorations: an in vitro study.
AB  - Grey discolouration around occlusal amalgam restorations has been found to be
      useful for the diagnosis of secondary caries. The aim of the present in vitro
      study was to establish the validity of grey discolouration of buccal and lingual
      enamel next to the approximal amalgam of class II restorations for the diagnosis
      of secondary caries. One hundred buccal and lingual areas next to the approximal
      parts of a class II filling in molars and premolars were included in the study.
      Fifty-one areas showed grey discolouration. Validation was performed against
      radiographs of transverse sections. Both radiolucencies and radiopacities were
      scored as being caries. The results were: sensitivity 92%, specificity 55%,
      positive predictive value 22% and negative predictive value 98%. It was concluded
      that grey discolouration of the approximal walls next to class II amalgam
      fillings is not useful for the detection of secondary caries, but the absence of
      grey discolouration gives a good prediction for the absence of secondary caries.
      This is in contrast to grey discolouration around occlusal amalgam restorations,
      which was considered to be useful for the diagnosis of secondary caries.

PMID- 8860029
TI  - Fluoride in the interdental area after two different post-brushing water rinsing
      procedures.
AB  - The aim of the present investigation was to study two post-brushing water rinsing
      procedures: (1) on fluoride (F) accumulation in approximal dental plaque, and (2)
      on F clearance in the interdental area. Twenty subjects participated first in the
      accumulation study, including three experimental periods (A, B and C), each
      lasting for 7 days. During period A, they brushed with a 0.32% NaF dentifrice for
      2 min, followed by a 1-min active mouth rinse with the toothpaste foam combined
      with 5 ml of water. During period B, the 2-min brushing was followed by three
      quick water rinses with 15 ml each. During period C, toothbrushing, which was
      carried out without any toothpaste, was followed by a 2-min active mouthrinse
      with 10 ml of a 0.05% NaF solution. All three procedures were performed in the
      morning (after breakfast) and in the evening (just before bedtime). The results
      showed that the accumulation of F in pooled approximal plaque after 7 days
      reached on average 2.7 times higher values after procedure A than B (p<0.001).
      Procedure C also resulted in more F in plaque than B (p<0.001). The same 20
      subjects participated in the clearance study on a separate occasion. When
      measuring the F concentration in the interdental area at 3 h after the
      application, procedure A resulted in a significantly higher F concentration than
      both toothbrushing B and mouth rinse C; the AUC was 2.2 times larger for A than
      for B (p <0.001). Thus, both the accumulation of F in approximal plaque and the
      clearance of F in the interdental area are related to the mode of water rinsing
      after toothbrushing.

PMID- 8860030
TI  - Salivary and urinary fluoride levels after 1-month use of fluoride-releasing
      removable appliances.
AB  - Forty children aged 8-10 years participated in this study. Half (n =20) of them
      used orthodontic appliances which contained fluoride-releasing devices embedded
      in the lingual surface of the appliance and the other half used orthodontic
      appliances prepared from a fluoride-releasing acrylic polymer. Prior to the
      adjustment of appliances and after 1, 7, 14, 21 and 30 days salivary and urinary
      samples were collected and the fluoride concentrations were determined. The mean
      fluoride release was highest during the first week. However, the values decreased
      considerably after that and the curves for the two groups became parallel. The
      results indicate that fluoride-releasing removable appliances could be useful for
      a prolonged release of low concentrations of fluoride without any systemic
      effect.

PMID- 8860031
TI  - Fluoride content of the enamel and dentine of human premolars prior to and
      following the introduction of fluoridation in New Zealand.
AB  - The fluoride content of the enamel and dentine of premolars was used as a
      determinant of the availability of ingested fluoride in New Zealand prior to and
      following the introduction of water fluoridation 40 years ago. Premolar teeth,
      which developed during the periods (PRE and POST respectively) under study, were
      selected from teeth extracted from 12 to 14-year-old children resident in
      different geographic areas in the country. The fluoride content, determined by
      multiple proton microprobe analyses, of surface enamel, deep enamel, and dentine,
      were for PRE teeth 440, 65 and 115, respectively. For POST teeth the mean values
      were significantly (p<0.001) higher, by 69, 29 and 102% respectively. The
      relevance of the change in fluoride content was assessed by comparison with
      published reports on the fluoride content of teeth developed in communities
      exposed to low (<0.5 ppm), optimal (1-2 ppm) and high (>3 ppm) naturally
      occurring fluoride levels in drinking water. The PRE teeth had a fluoride content
      associated with a low fluoride exposure and POST teeth with optimal fluoride
      exposure during tooth development. It was concluded that fluoride availability in
      New Zealand teeth had increased over the past 30 years but this increase is
      compatible with exposure of the community to optimal rather than excessive levels
      of ingested fluoride.

PMID- 8860032
TI  - Effect of citric acid clearance on the saturation with respect to hydroxyapatite
      in saliva.
AB  - Citric acid contained in beverages and foods is one of the main causes of enamel
      erosion. It was hypothesized that the clearance of citric acid from saliva would
      influence the degree of salivary saturation with respect to hydroxyapatite
      (OHAp). Ten subjects rinsed with 2% citric acid, pH 2.1, for 5s. Before and at
      1,2, 5, 10 and 15 min after the rinse, a small saliva sample was collected. The
      sample pH, ionic strength and the concentrations of ionized calcium, inorganic
      phosphate and citric acid were determined. The pH of the saliva decreased from
      7.21 + or - 0.40 (mean + or - SD) at time zero to a minimum of 6.46 + or - 0.88
      at 1 min after the rinse. It was back to baseline value after 15 min. The saliva
      was supersaturated with respect to OHAp at time zero. After the rinse with the
      citric acid the saturation level shifted to undersaturation in all individuals
      except one. At 1 and 2 min after the rinse the saliva was, on average,
      undersaturated. After 5 min the average saturation level was back to
      supersaturation. The individual differences were large. The correlations between
      the rate of clearance of citric acid during the 1 minute and the minimum degree
      of saturation with respect to OHAp at 1,2 and 5 min after the rinse were
      significant (r 0.84, r 0.76 and r 0.79, respectively). In conclusion, rinsing
      with citric acid will cause a decrease in the saturation level with respect to
      OHAp in a highly individual pattern.

PMID- 8860033
TI  - Effect of sodium hypochlorite treatment on remineralization of human root dentine
      in vitro.
AB  - Dentine consists simplified of mineral and of several organic components. Sodium
      hypochlorite (NaOCl) is a well-known nonspecific proteolytic agent capable to
      remove organic material. The aim of this study was to investigate the influence
      of organic material removal from artificial dentine lesions by means of NaOCl
      pretreatment on subsequent remineralization with and without fluoride. Human root
      dentine samples were demineralized in an acidic gel (pH = 5) at 37 degrees C for
      2 weeks. After 2 min of pretreatment with a 0.4, 2 or 10% NaOCl solution, the
      samples were remineralized in a 20 mM HEPES buffer (pH = 7) containing 1.5 mM
      Ca(2) and 0.9 mM phosphate with or without addition of 10 ppm F(-) as NaF at 37
      degrees C for 8 days. Mineral profiles were assessed by means of transversal
      microradiography after diol treatment to avoid shrinkage caused by drying. In a
      separate experiments the dentine contraction caused by 10% NaOCl was assessed.
      The contraction (negligible for sound dentine) was found to be about 12% for the
      lesions. The remineralization results showed that pretreatment with a 10% NaOCl
      solution for 2 min, increased lesion remineralization. After NaOCl treatment, the
      amount of accumulated mineral increased by about 27% without F in the
      remineralization solution, and by about 4% with 10 ppm in solution. The in vitro
      results suggest that removal of organic materials from dentine lesions is an
      interesting approach to enhance remineralization.

PMID- 8860034
TI  - Biological behavior of human dental pulp cells in response to carious stimuli
      analyzed by PCNA immunostaining and AgNOR staining.
AB  - The change in proliferative and metabolic activities of human dental pulp cells
      responding to carious stimuli was studied by means of immunohistochemical
      staining for proliferating cell nuclear antigen (PCNA) and silver-binding
      nucleolar organizer region (AgNOR) staining. We classified the pulp tissues into
      five groups according to the progression of dental caries, ranging from grade 0
      (the pulp of noncarious teeth) to grade 4 (the pulp of perforated carious teeth).
      PCNA-positive pulp cells were detected only in advanced dental caries (grades 3
      and 4), and the difference in immuno-positive rate was significant between the
      two grades (p <0.001). However, the mean number of AgNORs per nucleus increased
      even in the early phase of dental caries, significant differences being detected
      between grades 1 and 2 (p<0.005), 2 and 3 (p<0.005), and 3 and 4 (p<0.001). Our
      data suggested that the metabolic activity of dental pulp cells was enhanced in
      the early phase of dental caries. However, proliferation of pulp cells occurred
      later in small degrees during fully developed caries such as grades 3 and 4. The
      slow and weak response in cellular proliferation might contribute to the usual
      fragility of the pulp to various assaults including caries or pulpitis.

PMID- 8860035
TI  - Demineralization of dentine grooves in vitro.
AB  - Caries mainly occurs at retention sites for plaque such as pits, fissures,
      margins of restorations and interproximal sites. An in vitro model was developed
      to investigate dentine caries in narrow gaps. Forty bovine coronal dentine discs
      were covered with bonding agent. In 20 discs, two grooves, 200 and 340 mu m wide
      and 500 mu m deep, were sawn to mimic fissures. In the 20 other discs, a 1-mm
      wide groove was made and, after polyester sheets were placed against both walls,
      filled with composite. After curing of the composite and removal of the sheets,
      grooves of 22 mu m remained at the borders of the restoration. All grooves were
      exposed to 8% methylcellulose gel 0.1 M lactic acid at pH 4.8 for 1 week.
      Demineralization was determined by microradiography of sections sawn out of the
      center of the discs. The walls of the grooves showed subsurface lesions, which
      decreased in size towards the base of the grooves. The average mineral losses
      (vol % x mu m) at the entrance of the 22-, 200- and 340-mu m-wide grooves were
      1,112 (SD 370), 1,277 (293) and 1,277 (255), halfway down the groove 218 (150),
      659 (244) and 797 (207) and at the base of the groove 140 (88), 285 (145) and 504
      (205), respectively. Analysis of variance and Tukey's B test showed that the
      average mineral losses from grooves of different width and from sites at
      different depth were all significantly different at p<0.05 level, but not for the
      mineral losses from the entrance of the two wider grooves and from the two lower
      sites in the narrowest groove. The reduced mineral loss in the two narrower
      groove widths is assumed to be caused by the more limited inward diffusion of
      acids and outward diffusion of mineral ions through the methylcellulose gel.

PMID- 8860036
TI  - A theoretical evaluation of the role of precision and quality in clinical
      costings.
AB  - This study examines the nature of the problems caused by costing activities which
      focus on isolated treatments. The possible misallocation of resources is
      identified and a solution which accounts for full treatment until cure is
      postulated.

PMID- 8860037
TI  - Downsizing and financial performance in rural hospitals.
AB  - This article examines the association between downsizing and financial
      performance in a national sample of 797 U.S. rural hospitals from 1983-1988. The
      results indicate that downsizing occurred in about 15 percent of all rural
      hospitals and that a positive association between downsizing and financial
      performance was unconfirmed.

PMID- 8860038
TI  - Commentary: The future of rural hospitals in the United States.

PMID- 8860039
TI  - Medical staff leadership: a national panel survey.
AB  - Dramatic change in health care has challenged traditional medical staff
      governance and leadership. The role of medical staff leaders, particularly the
      chief of staff, and of the medical executive committee is explored through a
      national panel survey.

PMID- 8860040
TI  - A premerger profile of Columbia and HCA hospitals.
AB  - This article profiles the premerger marketing, management, and mission
      characteristics of the combined Columbia and Hospital Corporation of America
      (HCA) entity relative to local market hospitals. The findings show that the
      Columbia/HCA hospitals had fewer Medicaid patients, lower proportion of
      outpatient revenues, higher operating cash flow per bed, lower occupancy rates,
      lower salary expense per discharge, higher debt to total assets, fewer beds, and
      a higher case-mix index relative to local competitors.

PMID- 8860041
TI  - Patient and hospital characteristics associated with average length of stay.
AB  - This article examines the relationship between patient, hospital characteristics,
      and hospital average length of stay controlling for major disease categories. A
      constellation of patient and physician factors were found to be significantly
      associated with average hospital length of stay.

PMID- 8860042
TI  - A comparison of Utah hospital CEO turnover between 1973-1987 and 1988-1992.
AB  - This 1988-1992 study follows up on research on Utah hospital CEO turnover between
      1973-1987. For both periods, the highest turnover rate was transfer/promotion,
      followed by force out, retirement, death, and quitting. There was one change: For
      profits had significantly higher turnover than nonprofits. For both periods, the
      lowest rates of turnover and involuntary turnover were in the largest hospitals,
      all urban, all but one in a multihospital system, and one for-profit.

PMID- 8860043
TI  - Dimensions of accountability for not-for-profit hospitals and health systems.
AB  - This article examines four dimensions of accountability as they apply to not-for
      profit hospitals and health systems: political accountability, particularly
      relating to the retention of tax-exempt status; commercial accountability
      associated with the nonprofit hospital's role of selling low cost and high value
      health services to a variety of commercial payers; community accountability in
      terms of addressing community health and other social needs, and clinical/patient
      accountability in terms of access and quality outcomes.

PMID- 8860044
TI  - Personality patterns of health care and industry CEOs: similarities and
      differences.
AB  - The study discussed in this article revealed that a group of 30 hospital CEOs and
      a group of 32 general business CEOs shared similar work-related personality
      traits. Differences were found on only 2 of 20 traits: Hospital CEOs were
      significantly less "interested in working with details" and had a lower "need for
      rules and supervision." However, both groups of CEOs' personalities were
      different from those of managers in general.

PMID- 8860061
TI  - Statistical considerations in the use and analysis of single-subject designs.
AB  - Single-subject designs measure one individual's responses to some experimental
      manipulation. Statistical methods exist for validly estimating the effect of an
      intervention on a specific individual by using data from a single-subject design.
      However, without strong assumptions regarding how an intervention on one
      individual relates to its effects on others, the results from a single-subject
      design provide little useful information on the general utility of the
      intervention. Examination of a single subject cannot verify these assumptions.
      Correct analysis of data from such designs allows for the possibility of
      correlation among the observations and the modeling of any changes over time not
      related to an intervention effect. When data from single-subject designs are
      collected, the role of assumptions in both the analysis and the generality of
      conclusions must be frankly acknowledged. Research often develops in stages and
      the single-subject design can be useful in early stages for hypothesis
      generation.

PMID- 8860062
TI  - Japanese and American reports of randomized trials: differences in the reporting
      of adverse effects.
AB  - We sought to identify differences in the description of adverse drug experiences
      in reports of randomized clinical trials (RCTs) from the United States and Japan,
      using diclofenac and simvastatin as test drugs. Reports were identified in
      Medline (Index Medicus 1966-1990), EMBASE (Excerpta Medica 1974-1990), JAPICDOC
      (1979-1990), and JOIS-III (JMEDICINE 1980-1990). In each search keywords
      describing study design were paired with the drugs' generic names, chemical
      names, and development numbers. Twenty-seven U.S. reports (18 for diclofenac and
      9 for simvastatin) and 22 Japanese reports (17 for diclofenac and 5 for
      simvastatin) identified in these four databases were selected for review. For
      each paper we identified the relation of the article to the data (preliminary,
      primary, and secondary reports, reviews), the means of identifying adverse
      reactions, the principal outcomes of the trials, and a variety of descriptive
      measures relating to study design, authorship, and elements of presentation. With
      few exceptions, Japanese reports were not indexed in English-language databases,
      and studies from the United States were not carried out in the Japanese
      databases. The Japanese literature consisted exclusively of primary reports of
      clinical trials, whereas the U.S. literature was dominated by review articles and
      secondary reports of data from trials not fully published elsewhere. Japanese
      reports contained more detail on adverse experiences but reported principally
      those attributed to the drugs by attending clinicians. U.S. reports by contrast
      offered little detail but tended to include all adverse experiences, whether or
      not clinically attributed to drugs. A preponderance of U.S. articles reported
      significant differences between drugs in safety or treatment efficacy, whereas
      only one third of the Japanese articles did so for the same agents. Reports from
      both countries offered few details of the methods used to gather information on
      adverse drug experiences, and as a result the reported absolute frequencies of
      such events are difficult to compare between trials or to generalize to other
      settings. In conclusion, the reporting of adverse reactions in clinical trials is
      inadequate in both the United States and Japanese literature. The shortcomings
      are complementary in that reports of U.S. trials contain insufficient detail and
      Japanese reports do not interpret or synthesize experience. Clinical research
      into drug safety in both countries could be improved through the adoption of
      simple standards of clarity and consistency in the monitoring and reporting of
      drug adverse effects.

PMID- 8860063
TI  - Power calculation for the log rank test using historical data.
AB  - When planning a clinical trial that is to use the log rank test to compare
      survival in two groups, it is desirable to determine that the power of the test
      is adequate given the anticipated accrual rate and time, follow-up time, and
      survival functions S(1)(t) and S(2)(t). Often it is assumed that the ratio of the
      associated hazards is a constant, rho, and we want adequate power for a given
      value of rho. In this case S(2)(t) = S(rho)(1)(t), so that an assumption
      concerning S(1)(t) is required. If a Kaplan-Meier estimate S(1)(t) is available
      from a previous study, its use might be preferable to assuming a distribution of
      a particular form. In this note we show how such power calculations can be
      performed. Furthermore, since for any value of t, S(rho)(1)(t) is a random
      variable, the variance of power estimates calculated using it can be estimated.

PMID- 8860064
TI  - Comparison of once daily and twice daily nisoldipine as monotherapy in essential
      hypertension.
AB  - Twenty-four patients completed a dose ranging study of the effect of nisoldipine
      as monotherapy in the treatment of hypertension. This randomized double-blind
      study consisted of two crossover phases in each of which once and twice daily
      treatment were compared. In the first treatment phase the total daily dose of
      nisoldipine was 10 mg, which increased to 20 mg during the second phase. Trough
      blood pressure measurements were made 12/24 h postdose. During the first phase
      the blood pressure values following treatment with nisoldipine 5 mg twice daily
      were significantly lower than with 10 mg once daily. However, when the daily dose
      was increased to 20 mg there was no significant difference between the two
      treatment regimens. There was also no significant difference between nisoldipine
      5 mg twice daily and 10 mg twice daily but the results for 20 mg once daily were
      significantly lower than for 10 mg once daily. Four patients withdrew from the
      study because of adverse events, one while on placebo and three while on
      nisoldipine therapy. Between 33 percent and 47 percent of patients reported
      adverse events during nisoldipine treatment but the majority of adverse events
      reported were mild and did not require treatment withdrawal. Nisoldipine twice
      daily appeared to be more effective and better tolerated than once daily
      treatment for 24-h blood pressure control.

PMID- 8860066
TI  - Registry of multicenter clinical trials: 14th and 15th report 1992-1993.

PMID- 8860065
TI  - Preliminary results of beta-interferon treatment in the elderly.
AB  - The authors studied 26 patients presenting with chronic hepatitis C who were
      diagnosed by clinical and histological tests. Thirteen patients were treated with
      beta-interferon (3 x 10(6) IM for 2 months and consecutive 6 x 10(6) IM for 10
      months) every second evening, while the remaining 13 received aspecific
      treatment. Our results revealed normalization of transaminase accompanied by
      marked improvement of their clinical and histological pictures in 54 percent of
      the patients on beta-interferon. All the patients treated with beta-interferon
      were followed up for a 12-month drug-free period, after which the disease
      reappeared in 57 percent of the responders.

PMID- 8860067
TI  - Survival estimates in cystic fibrosis: snapshots of a moving target.

PMID- 8860068
TI  - Denmark to the rescue.

PMID- 8860069
TI  - Improved survival in the Danish center-treated cystic fibrosis patients: results
      of aggressive treatment.
AB  - We report survival data for Danish center-treated cystic fibrosis (CF) patients,
      covering the period 1974-1993 and using cross-sectional cumulative survival
      probability based on annual age-specific mortality rates. Analyses by age and by
      years after diagnosis were made. No significant differences were noted in the
      survival probability when patients were grouped according to sex or
      absence/presence of meconium ileus. The annual mortality rate for 1989-1993 was 0
      1.2%. Using the age-specific mortality rate for 1989-1993, we were unable to
      calculate the median survival probability because the curve did not fall below
      50% (age up to 45 years); however, it was possible to show that the survival
      probability for a newborn CF child to reach his 45th birthday was
      80.4%(confidence interval 76.5-84.6%). The median age at diagnosis was 0.63 years
      with no sex difference. The probability of surviving 40 years after the diagnosis
      of CF was made was 83.3% (confidence interval 80.1-86.6%). This is considerably
      higher than any other published survival probability. An early anti-Pseudomonas
      aeruginosa treatment regimen seemed important in achieving the observed improved
      survival.

PMID- 8860070
TI  - Effect of eosinophil peroxidase on airway epithelial permeability in the guinea
      pig.
AB  - Increased numbers of eosinophils and increased concentrations of plasma proteins
      have been found in the airways of patients with mild asthma. We used an intact
      guinea pig trachea model to investigate the role of eosinophil peroxidase (EPO)
      in altering the function of the airway epithelial barrier. EPO in the presence of
      hydrogen peroxide (H(2)O(2)) and bromide (Br(-)) catalyzes the production of
      hypobromous acid (HOBr), which is felt to have a toxic effect on airway
      epithelial cells. An intact guinea pig trachea was mounted on an apparatus in a
      way that would allow the tracheal epithelium to be exposed to different
      solutions. Following these exposures, a test solution containing (14)C-sucrose
      (S), (3)H-inulin (I), and FITC-dextran-20 (D) was placed in the tracheal lumen
      and positioned in the center of the segment for 90 minutes. Flux of these
      molecules across the epithelial barrier into a bath was measured, and the
      permeability (P) was calculated for each molecule to quantify epithelial barrier
      function. Light and electron micrographic studies were performed to assess
      cellular damage. We found that there was a dose response to EPO (in the presence
      of fixed amounts of H(2)(O)(2) and Br(-)). EPO at 7.3 x 10(-7) M caused no
      increase in P over controls (Ringer's solution alone) for S, I, or D (P> 0.05),
      whereas EPO at 2.7 x 10(-6) M caused a significant increase in P over controls (P
      = 0.008) for all test molecules. Light and electron micrographs of the latter
      tracheas showed no evidence of microscopic changes despite the increased P.
      Further testing verified that the increase in permeability was caused by the EPO
      catalyzed reaction and not the individual substrates themselves, and that the
      reaction was inhibited by a peroxidase inhibitor. We conclude that EPO can alter
      the barrier function of the airway epithelium before gross cellular damage
      becomes visible. We hypothesize that changes in the tight junctions are
      responsible for the alteration in the barrier function of the airway epithelium
      and that this may play an important role in the pathophysiology of mild asthma.

PMID- 8860071
TI  - Effect of positioning on pulmonary function of newborns: comparison of supine and
      prone position.
AB  - The effect of positioning on pulmonary function has been previously evaluated,
      and the prone position has been reported to be preferable for neonates with
      various respiratory diseases. Studies in healthy neonates have yielded
      conflicting results. Using a crying pulmonary function test, we examined the
      effect of positioning on pulmonary function in healthy full-term neonates. Thirty
      nine infants with a mean birthweight (+/- SD) of 3,140 +/- 379 g and a mean
      gestational age (+/- SD) of 39.8 +/- 1.6 weeks were investigated during the first
      6 hours of life. Measurements were obtained in both supine and prone positions
      using a computerized volume-flow system. There were statistically significant
      decreases in crying vital capacity (CVC) and peak expiratory flow rate (PEF) in
      the prone compared with the supine position. However, there were no significant
      differences in forced expiratory flow rate at 75% (V(75)), 50% (V(55)), and 25%
      (V(25)) of vital capacity between the two positions. These results suggest that
      prone positioning decreases lung volume and increases resistance of upper
      airways. We conclude that healthy neonates should be in the supine posture for
      optimal ventilation.

PMID- 8860072
TI  - Temporal relationship between pauses in nasal airflow and desaturation in preterm
      infants.
AB  - Physiological recordings were undertaken to study the temporal relationship
      between apnea, defined as pauses in nasal airflow (PNA), and desaturation in
      preterm infants. Seventeen infants with a history of apnea of prematurity were
      studied on 21 occasions. Median (range) birthweight was 1,180 g (575-2,475) and
      gestation was 30 weeks (26-33). Median age at time of study was 10 days (range, 2
      52). Arterial beat to beat oxygen saturation (SaO(2)), photoplethysmographic
      waveform, electrocardiogram, abdominal and ribcage breathing movements, and nasal
      airflow were recorded. Falls in SaO(2) > or = 3% occurring during or after a PNA
      > or = 4 seconds were recorded. Episodes of periodic breathing were excluded from
      this analysis. Four hundred and sixteen episodes of PNA and desaturation were
      analyzed. Application of a definition of "outliers" for non-parametric data
      suggested an association when the desaturation occurred up to 7.20 seconds after
      the end of the PNA for infants nursed in air. For infants on oxygen treatment, a
      temporal association was suggested when desaturation occurred up to 9.76 seconds
      after the end of PNA.

PMID- 8860073
TI  - Evaluation of pulmonary function and polysomnography in obese children and
      adolescents.
AB  - Obese adults have an increased prevalence of pulmonary disorders. Although
      childhood obesity is a common problem, few studies have evaluated the pulmonary
      complications of obesity in the pediatric population. We, therefore, performed
      pulmonary function tests (PFTs), polysomnography, and multiple sleep latency
      tests (MSLTs) in 22 obese children and adolescents [mean age, 10 +/- 5 (SD)
      years; 73 percent female; 184 +/- 36 percent ideal body weight], none of whom
      presented because of sleep or respiratory complaints. PFTs were normal in all but
      two subjects. Ten (46 percent) subjects had abnormal polysomnograms. There was a
      positive correlation between the degree of obesity and the apnea index (r = 0.47,
      P < 0.05), and an inverse correlation between the degree of obesity and the
      Sa0(2) nadir (r = -0.60, P < 0.01). The degree of sleepiness on MSLT correlated
      with the degree of obesity (r = -0.50, P < 0.05). We conclude that obese children
      and adolescents have a high prevalence of sleep-disordered breathing, although in
      many cases it is mild. Obstructive sleep apnea syndrome (OSAS) improved following
      tonsillectomy and adenoidectomy. We recommend that pediatricians have a high
      index of suspicion for OSAS when evaluating obese patients, and that
      polysomnography be considered for these patients.

PMID- 8860074
TI  - Adjustment of bronchoalveolar lavage volume to body weight in children.
AB  - To define the amount of epithelial lining fluid (ELF) that is recovered during
      bronchoalveolar lavage (BAL) in the pediatric age group, we measured albumin and
      urea concentrations in serum and BAL fluid (BALF) of 37 children aged 3-15 years
      without bronchopulmonary disease. The children were studied while undergoing
      elective surgery for non-pulmonary illnesses using a BAL protocol adjusted to
      body weight. ELF increased with age in proportion to increases in lavage volume.
      When corrected for the child's weight, approximately 20 mu l ELF/kg body weight
      were recovered throughout the age range. ELF derived by determining albumin or
      urea concentrations in BALF were significantly correlated; however, considerable
      variability was observed in older children when the urea method was used. This
      was likely due to the increase in dwell time that is known to affect urea
      concentrations in BALF. In children ELF/100 ml BALF was higher than in adults,
      suggesting a greater permeability of the alveolar membrane in children. These
      data show that a BAL protocol adjusted to body weight will yield constant
      fractions of ELF in children aged 3-15 years. These results should facilitate the
      comparison of BALF constituents in children of different age groups.

PMID- 8860075
TI  - Late onset central hypoventilation syndrome.

PMID- 8860076
TI  - KID syndrome associated with elevated sweat chloride.

PMID- 8860077
TI  - Bronchoscopic appearances of congenital lobar emphysema.
AB  - Although decreased bronchial cartilage is found in 50% of cases of congenital
      lobar emphysema (CLE), it can only be surmised that this defect produces a ball
      valve effect with consequent overinflation. We describe the flexible
      bronchoscopic features of CLE in a 3-year-old child. The observed airway patency
      during inspiration, and dynamic airway collapse on expiration suggests that
      bronchomalacia contributes to lung overinflation in these cases.

PMID- 8860096
TI  - Glycogen synthase polymorphism, insulin resistance and hypertension.
AB  - The A(2) allele of the human glycogen synthase gene may be associated with
      hypertension in diabetic and non-diabetic Finnish subjects. The prevalence of the
      A(2) allele was investigated in 64 non-diabetic hypertensive subjects with
      borderline hypertension or established hypertension. Ambulatory blood pressure
      was performed on all subjects. Insulin sensitivity index (S(I)) was determined in
      subjects with borderline hypertension. The DNA fragment containing the XBaI
      restriction site was amplified by the polymerase chain reaction, digested by the
      XBaI enzyme and compared by gel electrophoresis with a positive control from
      Finland. Mean age +/- SD for age, S(I) and ambulatory blood pressure were
      respectively: 39 +/- 10 yrs, 60 +/- 30 min(-1)(nmol/mL) and 132 +/- 7/ 83 +/- 6
      mmHg. Sixteen of the subjects were insulin resistant as determined by S(I) <70.0
      and they had significantly higher BP and BMI than insulin sensitive subjects. The
      A(2) allele of the glycogen synthase was not detected in any subject. This
      suggests that the relation between the XBaI polymorphism of the glycogen synthase
      gene, insulin resistance and elevated blood pressure may be restricted to a
      limited and genetically uniform Finnish population.

PMID- 8860098
TI  - Parathyroid hypertensive factor predicts efficacy in the treatment of essential
      hypertension with verapamil.
AB  - Parathyroid hypertensive factor (PHF) is a circulating hypertensive factor,
      levels of which are inversely related to renin profile. Given this relationship,
      it was hypothesized that a PHF level might serve as an alternate predictor of
      antihypertensive efficacy in hypertensive patients, avoiding the difficulties
      associated with renin profiling. To test this hypothesis, thirty patients with
      essential hypertension were placed on 240 mg once daily of a slow release
      verapamil preparation for a period of one month following a one month run-in
      period. Results showed an average reduction in mean arterial pressure (MAP)of -7
      mmHg (range -5 to - 18) and an average reduction in PHF of -4 mmHg (range 7 to 
      28). Pre-treatment PHF level correlated with the blood pressure response to
      verapamil (r = -0.61, p = 0.0004). There was no correlation between any index of
      renin status and blood pressure. The only other correlation of note was between
      normalized, ionized calcium and change in blood pressure (r = -0.46, p =0.02). In
      a forward stepwise multivariate model with MAP as the dependent variable, PHF and
      normalized, ionized calcium levels were the only biochemical or demographic
      predictors of response to verapamil. These results suggest that PHF level may be
      useful in determining the initial choice of antihypertensive agent in
      hypertensive patients.

PMID- 8860097
TI  - Adverse effects on risk of ischaemic heart disease of adding sugar to hot
      beverages in hypertensives using diuretics. A six year follow-up in the
      Copenhagen Male Study.
AB  - Non insulin dependent diabetes mellitus (NIDDM) and essential hypertension (EH)
      are two of several manifestations of the insulin resistance syndrome. Although
      subjects with NIDDM and subjects with EH share a common defect in carbohydrate
      metabolism, only diabetics are advised to avoid sugar. We tested the theory that
      an adverse effect of diuretics treatment in men with EH with respect to risk of
      ischaemic heart disease (IHD) would depend on the intake of dietary sugar using
      sugar in hot beverages as a marker. The cohort consisted of 2,899 men from the
      Copenhagen Male Study aged 53-74 years (mean 63) who were without overt
      cardiovascular disease. Potential confounders were: age, alcohol,smoking,
      physical activity, body mass index, blood pressure, fasting lipids, cotinine,
      NIDDM,and social class. A total of 340 men took antihypertensives; 211 took
      diuretics (95% thiazides and related agents), and 129 used other
      antihypertensives. During 6 years, 179 men (6.2%) had a first IHD event. Among
      the 340 men taking antihypertensives, the incidence rate was 11%. Diuretics use
      was associated with a high risk of IHD in hypertensive men with a relatively high
      intake of dietary sugar; the cumulative incidence rate was 22%; in diuretics
      treated men with a low intake of sugar, the rate was 7%. After controlling for
      potential confounders, relative risk (95% ci.) was 3.1(1.3-7.6), p = 001. Among
      the 129 men who took other forms of antihypertensive drugs, the IHD incidence
      rate was 8%, and independent of the intake of sugar. The results indicate that
      the risk of IHD in hypertensives using diuretics is associated with intake of
      dietary sugar, which may explain at least some of the discouraging effects of
      antihypertensive agents on the reduction of risk of IHD.

PMID- 8860099
TI  - Low dose of ACE-inhibitor enhances sodium excretion in volume expanded patients
      with borderline hypertension.
AB  - The purpose of the present study was to separately investigate the effects of two
      different dosages of captopril on pressor, vascular and humoral response to acute
      extracellular volume expansion in patients with borderline hypertension (BHT).
      Thirty-five patients were randomly allocated in two groups undergoing acute
      saline infusion (0.40 ml/min/kg for 45 min and 0.15 ml/min/kg for 75 min)before
      and after a 7-day period of treatment with either placebo or captopril at the
      dose of 12.5 (LD-CAP) or 50 mg (HD-CAP) twice a day. At baseline the effects of
      LD-CAP were limited to an increase in PRA and to a decrease in plasma aldosterone
      whereas HD-CAP decreased systolic and diastolic blood pressure (SBP, DBP),
      forearm vascular resistance (FVR) and increased venous distensibility (VV(30)) as
      well. After saline loading patients treated with HD-CAP showed an increase in
      SBP, DBP not observed in patients allocated to LD-CAP. Urinary sodium excretion
      in response to NaCl loading was selectively enhanced by LD-CAP (+25%) whereas HD
      CAP did not (+6.3%). The present data suggest that low-doses of ACE-inhibitors
      acting through a selective blockade of RAA not associated with hemodynamic
      changes can enhance the natriuretic response to acute volume expansion in
      borderline hypertensives.

PMID- 8860100
TI  - Arachidonate metabolites and serotonin contraction of femoral arteries from DOCA
      salt hypertensive rats.
AB  - Serotonin stimulates phospholipase A(2)(PLA(2)) leading to the production of
      prostaglandin products, several of which are vasoconstrictors. We hypothesised
      that the elevated vascular responsiveness to serotonin in deoxycorticosterone
      acetate (DOCA)-hypertensive rats is due in part to augmented production of
      vasoconstrictor cyclooxygenase products (e.g. PGF(2)alpha). Denuded helical
      strips of femoral arteries from DOCA-salt hypertensive rats (SBP 183 +/- 7 mmHg)
      and normotensive control rats (SBP 115 +/- 2) were used in all experiments.
      EC(50) values for several agonists were significantly reduced in DOCA arteries
      compared with controls (in mu mol/L, control vs. DOCA): PGF(2)alpha (0.99 vs.
      0.23), PGE(2) (0.72 vs. 0.22), arachidonate (1.52 vs. 0.73), serotonin (0.19 vs.
      0.07), noradrenaline (0.029 vs. 0.013), KCl (40.1 vs. 27.0 mmol/L) and AlF(4)
      (2.3 vs. 1.4 mmol/L). Treatment with indomethacin (14 mu mol/L) inhibited the
      responses to serotonin in DOCA arteries (EC(50) values 0.07 untreated vs. 0.70)
      and eliminated the responses to arachidonate but did not affect KCl or AlF(4
      )contractions. Cyclooxygenase inhibitors shifted concentration response curves to
      serotonin in sham and DOCA tissues equally. Thus increased sensitivity to
      serotonin in DOCA arteries persisted following cyclooxygenase blockade.
      Therefore, although arachidonate products contribute to the serotonergic
      contraction in femoral arteries, the augmented response in arteries from DOCA
      hypertensive rats is not due to increased production of or sensitivity to
      cyclooxygenase products. Furthermore,arachidonate metabolites do not contribute
      to the contraction induced by either AlF(4-)or KCl in this preparation.

PMID- 8860101
TI  - Effect of low dietary calcium intake on blood pressure and pressure natriuresis
      response in rats: a possible role of the renin-angiotensin system.
AB  - Dietary Ca is an important modulator of blood pressure in humans and rats. Since
      the kidney plays a key role in the pathogenesis of hypertension, the effects of a
      low Ca diet (0.01% Ca) on blood pressure and pressure natriuresis response were
      studied in normotensive Sprague-Dawley rats. In addition, a possible role of the
      renin-angiotensin system in the development of hypertension and an altered
      pressure natriuresis response resulting from low dietary Ca intake was examined.
      In the low Ca diet group, systolic blood pressure measured by the tail-cuff
      method was significantly higher than in the normal Ca diet group (1,1% Ca) 1 week
      after the diet (1 13.0 +/- 7.1 vs. 105.0 +/- 9.5mmHg, p < 0.05). After 4 weeks,
      the hypertension was more pronounced. Low dietary Ca intake significantly
      inhibited the water and sodium excretory responses to acute elevation of renal
      perfusion pressure by tightening an infrarenal aortic constriction. Treatment
      with an inhibitor of angiotensin-converting enzyme, captopril (30 mg/kg/day),
      completely abolished the elevation of blood pressure and attenuated the reduced
      pressure natriuresis response observed in Ca-deficient rats. Although plasma
      renin activity was not different between the low and normal Ca diet groups after
      the 2-week dietary regimen, the pressor response to angiotensin II was enhanced
      by 30% in the low Ca diet group and there was a significant difference in the
      pressor response between the two groups. These results suggest a possible
      involvement of the renin-angiotensin system in the development of hypertension
      and an inhibitory effect on the pressure natriuresis response caused by low
      dietary Ca intake, via an enhanced sensitivity to angiotensin II.

PMID- 8860102
TI  - Antioxidants, atherosclerosis and thrombosis.

PMID- 8860103
TI  - Enhanced accumulation of free fatty acids in experimental focal cerebral
      ischemia.
AB  - Cerebral ischemia is well known to cause an increase in the level of free fatty
      acids (FFAs) in rodent species. Such FFA accumulations may signal regional lipid
      membrane damage and are postulated to participate in the pathogenesis of
      progressive infarction after cerebral ischemia. In this study we have examined
      the regional levels of FFAS in the cortices of cats after 8 h of middle cerebral
      artery occlusion. The levels of specific FFAs (palmitic, stearic, and oleic
      acids) were 1.5 and 2.0 times higher in the penumbral and dense ischemic regions,
      respectively, than those in the non-ischemic contralateral region. Although no
      significant differences were found between the penumbra and dense ischemic
      regions in the levels of arachidonic acid, the levels of docosahexaenoic acid in
      both of these regions were significantly higher than those in the contralateral
      region (P < 0.05). These results suggest that enhanced accumulation of FFAs are
      regionally distributed after focal ischemia and may contribute to neuronal damage
      after focal cerebral ischemia in non-rodent species.

PMID- 8860104
TI  - Dietary lipid affects phospholipid fatty acid compositions, eicosanoid production
      and immune function in Atlantic salmon (Salmo salar).
AB  - Atlantic salmon (Salmo salar) post-smolts were fed diets containing either Fosol
      (FO), a North Sea fish oil, sunflower oil (SO), linseed oil (LO) or Marinol K
      (MO), a southern hemisphere fish oil rich in 20:5(n-3) for 12 weeks. A macrophage
      enriched leucocyte preparation was obtained from head kidney and the fatty acid
      compositions of the individual membrane phospholipids measured. In general
      phospholipids from SO- and LO-fed fish had increased 18:2(n-6), 20:2(n-6) and
      20:3(n-6) compared to the fish oil treatments while LO-fed fish had lower 20:4(n
      6) than any other dietary treatment. Fish fed LO also had increased 18:3(n-3),
      18:4(n-3), 20:3(n-3) and 20:4(n-3). The 20:5(n-3) content of kidney macrophage
      enriched leucocyte phospholipids was highest in MO-fed fish followed by FO- and
      LO-fed fish with the lowest level in fish fed SO. The overall effect on the ratio
      of eicosanoid precursors, 20:4/20:5, showed the highest value in SO-fed fish and
      the lowest in fish fed LO. Production of LTB5 by kidney macrophage-enriched
      leucocytes stimulated with A23187 was highest in MO-fed fish and lowest in those
      fed SO. Production of LTB4 was greatest in SO-fed fish and lowest in fish fed LO.
      Serum Ig levels were significantly affected by dietary treatment with highest
      values in fish fed FO and SO and lowest in fish fed MO and LO.

PMID- 8860105
TI  - An evaluation of garlic and onion as antithrombotic agents.
AB  - Garlic (Allium sativum) and onion (Allium cepa) have been evaluated as possible
      antithrombotic agents. Rats were given aqueous extracts of garlic and onion,
      orally or intraperitoneally, daily for a period of 4 weeks after which the rats
      were sacrificed. The blood was collected from the heart without anticoagulant and
      the serum was prepared. The level of thromboxane B2 (TXB2) in the serum was
      measured by radioimmunoassay. TXB2 levels in serum of rats treated with the low
      dose of aqueous extract of garlic (50 mg/kg) was significantly inhibited
      regardless of the mode of administration (orally or intraperitoneally). At the
      high dose of garlic and onion (500 mg/kg), a further decrease of TXB2 levels in
      the serum of the rats was observed. Boiled garlic and onion at high concentration
      (500 mg/ kg) had very little effect on TXB2 synthesis. This shows that garlic and
      onion should be consumed in a raw rather than cooked form in order to achieve a
      beneficial effect. Boiling of these plants may cause the decomposition of the
      potential antithrombotic ingredient present in these herbs. Garlic was found to
      be more potent than onion in lowering the TXB2 levels. A high dose of garlic and
      onion produces toxicity in the rats (unpublished observation). These results show
      that garlic and onion can be taken frequently in low doses without any side
      effects, and can still produce a significant antithrombotic effect.

PMID- 8860106
TI  - Increase in prostaglandin bioavailability precedes the onset of human
      parturition.
AB  - The traditional paradigm that prostaglandins (PGS) are of central importance in
      the initiation of labor has been challenged. A group of investigators has
      recently reported that the amniotic fluid concentrations of PGE(2) and PGF(2
      alpha) increase only late in the course of labor implying that "the accumulation
      of prostaglandins in amniotic fluid is an after-effect of labor and not
      indicative of a role of these compounds in the initiation of human parturition."
      The present study was conducted to determine whether amniotic fluid prostaglandin
      concentrations increase prior to the onset of human labor, the central question
      in this controversy. Three amniocenteses were performed in 17 women with
      intrahepatic cholestasis of pregnancy -- the first two prior to the onset of
      labor and the third during early spontaneous labor. PGE(2) and PGF(2 alpha) were
      measured with sensitive and specific radioimmunoassays. Amniotic fluid
      concentrations of PGE(2) and PGF(2 alpha) increased prior to the onset of
      spontaneous labor. An additional increase in the concentrations of PGE(2) and
      PGF(2 alpha) was found in samples obtained in early labor. We conclude that an
      increase in prostaglandin bioavailability precedes the onset of spontaneous human
      parturition.

PMID- 8860107
TI  - Effects of Fe(2+), Zn(2+), Cu(2+) and Se(4+) on the synthesis and catabolism of
      prostaglandins in rabbit gastric antral mucosa.
AB  - Effects of Fe(2+), Zn(2+), Cu(2+) and Se(4+) on the synthesis and catabolism of
      prostaglandins (PGs) in rabbit gastric antral mucosa were examined. Fe(2+)
      inhibited the cyclooxygenase activity in the microsomal fraction. Zn(2+)
      suppressed the endoperoxide E(2) isomerase activity in the microsomal fraction
      and the 15-hydroxy PG dehydrogenase (PGDH) activity in the cytosolic fraction.
      Cu(2+) stimulated the cyclooxygenase activity, inhibited the PGDH activity and
      possibly induced non-enzymatic reduction of PGG(2) or PGH(2) to PGF(2 alpha)
      Se(4+) possibly induced the non-enzymatic reduction of PGG(2) or PGH(2) to PGF(2
      alpha), as well as Cu(2+). These results suggest that Fe(2+), Zn(2+), Cu(2+) and
      Se(4+) can be modulators of the gastric antral mucosal PG levels by affecting the
      PG synthesizing enzymes, PG catabolizing enzyme and/or non-enzymatic reduction of
      PGG or PGH to PGF.

PMID- 8860108
TI  - Activation of neutrophil-like HL-60 cells by prostaglandin E2.
AB  - The effect of prostaglandins on neutrophil activation has been studied using the
      human promyelocytic leukemic cell line HL-60, differentiated with dimethyl
      sulfoxide (DMSO). Prostaglandin E(2) (PGE(2)) directly stimulated HL-60 cell
      aggregation with an EC(50) value of 30 nM. Studies with prostanoid receptor
      selective agonists suggest that the activation of HL-60 cells by PGE(2) was
      mediated via the EP(2) receptor. Human neutrophils did not aggregate in response
      to PGE(2), but PGE(2) inhibited the N-formyl-methionyl-leucyl-phenylalanine
      (FMLP)-stimulated increase in intracellular calcium ([Ca(2+)i]) in both
      neutrophils and HL-60 cells. In contrast with the aggregation response to FMLP
      the aggregation response of HL-60 cells to PGE(2) was independent of
      extracellular calcium and did not involve mobilization of intracellular calcium.

PMID- 8860109
TI  - Some adverse cardiodynamic effects of prostaglandin E2 in congestive heart
      failure.
AB  - The cardiodynamic effects of prostaglandin E(2) (PGE(2)) were studied in both
      healthy sheep and in animals with congestive heart failure (CHF). Merino ewes
      were equipped surgically with high fidelity micromanometers and left ventricular
      pressures measured. Heart rate, left ventricular systolic and end-diastolic
      pressures, +dP/dt and T(ln) were calculated on a computer from the recorded
      pressure curves. The paired t-test was used to determine the statistical
      significance of the differences. PGE(2) (25 mu g/kg) significantly improved the
      cardiac contractility and relaxation rate of healthy sheep and significantly
      reduced the heart rate, while the loading conditions under which the heart
      operates were not significantly affected. In contrast to healthy sheep, PGE(2)
      significantly reduced the contractility and relaxation rate of sheep with
      congestive heart failure and significantly increased the preload while heart rate
      and afterload were significantly reduced. The study suggests that despite the
      promising vasodilatory, positive inotropic and relaxation rate actions of PGE(2)
      in normal hearts, PGE(2) might not be a suitable therapeutic agent for CHF,
      because of the worsening effect it has on the cardiodynamics and loading
      conditions of the failing heart.

PMID- 8860110
TI  - Oxygen deprivation and reoxygenation augment prostacyclin synthesis in cultured
      ventricular myocytes.
AB  - Prostacyclin production in cultured cardiomyocytes is not induced by cellular ATP
      depletion per se, suggesting that the mechanism of ischemic injury is more
      complex. In the present study we subjected cultured ventricular myocytes to
      'simulated ischemia' followed by reoxygenation. A slight increase in 6-keto-PGF(1
      alpha) (the stable metabolite of PGI(2)) was found during 'ischemia', which
      continued to increase markedly during reoxygenation. PGE(2) levels were
      pronouncedly enhanced during ischemia but decreased during reoxygenation, and
      TXB(2) levels remained undetectable throughout. These findings reflect a
      cardiomyocyte response to anoxic injury, suggesting that they act to protect
      against cardiac injury by producing the potent vasodilators PGI(2) and PGE(2)
      during ischemia and reoxygenation.

PMID- 8860111
TI  - Changes in peripheral hemodynamics and vasodilating prostaglandins after high
      dose short-term ibuprofen in chronically treated hypertensive patients.
AB  - The use of cyclooxygenase inhibitors has been seen to reduce the efficacy of many
      antihypertensive drugs. However, cyclooxygenase inhibitors are normally non
      selective because they affect both vascular tissue, where the endothelial
      prostanoids exert principally a vasodilatory action, and the kidneys, where they
      also play an important role in regulating hydroelectrolytic metabolism by
      redistribution of intraparenchymal flow. To evaluate the relative importance of
      vascular district in the hypertensive patient, we administered ibuprofen - a drug
      acting with only a minimal antagonist activity. A group of 20 male hypertensives
      were randomly allocated, according to a single-blind protocol, to treatment with
      amlodipine (A, 10 mg/day) or lisinopril (L, 20 mg/day). Blood pressure was
      significantly reduced after 30 days, with a mean difference of -21.75 mmHg for
      systolic blood pressure (SBP) (95% confidence interval (Cl): -27.46 to -16.04; P<
      0.0001) and -14.15 mmHg for diastolic blood pressure (DBP) (95% Cl: -17.13 to 
      11.17; P< 0.0001). Brachial artery compliance showed a mean increase of 1.657 x
      10(-7) dyn-1 cm(4) (95% Cl: 1.188 to 2.126; P<0.001), and forearm resistances
      showed a mean decrease of -41.973 mmHg ml(-1)s (95% Cl: -75.479 to -8.467; P =
      0.017). Changes in compliance were significantly related to those in SBP (r= 
      0.546; P= 0.013). The administration of ibuprofen (400 mg, three times a day for
      3 days) was accompanied by a slight but significant increase in SBP, but not in
      brachial artery compliance or forearm resistances. Only SBP was affected, showing
      a mean increase of 4.25 mmHg (95% Cl: 1.26 to 7.24; P = 0.008). There was also
      reduced urinary excretion of PGI(2) and TXA(2) metabolites. The mean change in 6
      keto-PGF(1 alpha) and 2,3-dinor-6-keto-PGF(1 alpha) was 45.71 ng per g urinary
      creatinine (uCr) (95% Cl: -0.16 to-91.25; P= 0.049) and -73.17 ng (g uCr)(-1)
      (95% Cl: -38.81 to -107.53; P<0.001), respectively. The mean decrease in TXA(2)
      catabolites was highly significant: -39.2 ng (g uCr)(-1) (95% Cl: -18.17 to
      60.22; P< 0.001) and -102.87 ng (g uCr)(-1) (95% Cl: -61.86 to -143.88; P< 0.001)
      for TXB(2) and 2,3-dinor-TXB(2), respectively. Our study highlighted an inverse
      correlation between changes in blood pressure and those in urinary 2,3-dinor-6
      keto-PGF(1alpha) excretion, irrespective of antihypertensive regimen. This
      suggests that, in the hypertensive patient treated with NSAIDs, inhibition of
      vascular prostanoid synthesis may play an important role in countering the
      efficacy of an important vascular tone regulatory mechanism.

PMID- 8860112
TI  - Inotropic, chronotropic, and radioligand binding characteristics of leukotriene
      B4 in cardiac myocyte, papillary muscle, and membrane preparations.
AB  - Cardioprotective effects of dietary fish oil consumption have been attributed to
      the substitution of eicosapentaenoic acid (EPA) for arachidonic acid (AA) in
      cellular membranes. This substitution blocks the formation of leukotriene B(4)
      (LTB(4)) which is elaborated locally in the area of ischemic myocardium. We
      studied the in vitro inotropic, chronotropic, and radioligand binding
      characteristics of LTB(4) to gain potentially important insights into the
      mechanisms involved in the cardioprotective effect of EPA. LTB(4) was a
      concentration-dependent and reversible negative inotrope in isolated papillary
      muscle preparations. LTB(4) significantly blocked the positive inotropic effect
      of Bay K 8644 (BK) (calcium channel regulator) on papillary muscles and the
      positive chronotropic effect of BK on spontaneously beating neonatal cardiac
      myocytes. LTB(4) had no direct effect on [(3)H]PN200-110 binding to cardiac
      sarcolemmal L-type calcium channels or [3H]ryanodine binding to cardiac SR
      calcium release channels. These studies support a potentially important indirect
      effect of LTB(4) on myocardial E-C coupling.

PMID- 8860142
TI  - Ameloblastic fibromas and related tumors in cattle.
AB  - This article concerns rare odontogenic tumors that occur predominantly in the
      mandibular incisor region of young cattle and which have often in the past been
      referred to as ameloblastomas, or as the outdated synonym, adamantinoma. Twenty
      two examples from the literature and two new ones were studied. Six consisted of
      epithelial islands which resembled those of ameloblastoma but which were located
      within a cellular fibrous connective tissue that was the second component of the
      tumor; these mixed odontogenic tumors therefore represented ameloblastic
      fibromas, not ameloblastomas. Eight consisted of a combination of ameloblastic
      fibroma and odontoma and therefore were ameloblastic fibro-odontomas, and one was
      apparently malignant (ameloblastic fibro-odontosarcoma). Excluding this last
      lesion, these tumors should respond well to enucleation, like their human
      counterparts but, to confirm this hypothesis, the margins of future examples
      should be carefully examined to determine that they are well-demarcated, not
      invasive. The microscopic features of the remaining 9 tumours could not be
      evaluated adequately, while another 17 tumors in cattle and water buffalo
      reported briefly could not be studied to any extent because of insufficient
      information.

PMID- 8860143
TI  - The central odontogenic fibroma and the hyperplastic dental follicle: study with
      Picrosirius red and polarizing microscopy.
AB  - The central odontogenic fibroma (COF) is an uncommon odontogenic tumor in which
      the microscopic appearance is similar to that of the hyperplastic dental follicle
      (HDF). Distinction between these lesions is based mainly on their clinical and
      radiologic features. The collagen of 5 cases of COF and 13 cases of HDF was
      studied histochemically by staining sections with Picrosirius red and examining
      them by polarizing microscopy. Polarization colors of the collagen fibers of the
      lesions were recorded according to their width. While no differences were seen
      between the polarization colors of thin fibers (<0.8 mm) in both lesions, the
      polarization colors of thick fibers (1.6-2 mm) of COF were significantly more
      green and greenish-yellow as compared with those of HDF. These findings suggest
      that the Picrosirius red polarization method can be used as a diagnostic tool to
      differentiate between COF and HDF..

PMID- 8860144
TI  - Cyclosporin- and nifedipine-induced gingival overgrowth in renal transplant
      patients: correlations with periodontal and pharmacological parameters, and HLA
      antigens.
AB  - The factors associated with cyclosporin A (CsA)- and nifedipine (Nif)-induced
      gingival overgrowth were investigated in 113 renal transplant recipients
      receiving CsA alone (Group 1) [n = 61], CsA and Nif (Group 2) [n = 28], or
      azathioprine (Aza) (Control Group) [n = 24]. Periodontal and pharmacological
      parameters were assessed for each patient. The patients with a gingival
      overgrowth index (GOI) score >1 were considered responders (R); those with a
      score </= 1 were non-responders (NR). Gingival overgrowth occurred in 33.7% of
      the patients in Groups 1 and 2; 60% of the responders were receiving CsA+Nif. In
      R, no relationship was found between the GOI and the periodontal and
      pharmacological parameters, and although there was a trend towards an increased
      presence of HLA-A19 antigen (chi-square=4.40; P=0.04; RR=2.86), no significant
      difference was found between R and NR (Pc>0.05). It is concluded that the
      prevalence and severity of gingival overgrowth are greater in patients receiving
      CsA+Nif. As overgrowth appeared to be unrelated to local irritants, gingival
      inflammation or pharmacological parameters, it may be related to individual
      susceptibility.

PMID- 8860146
TI  - A study on betel quid chewing behavior among Kaohsiung residents aged 15 years
      and above.
AB  - A telephone survey was used to study betel quid chewing behavior of Kaohsiung
      residents aged 15 and above in early 1991. Among the 1,162 subjects, 154 (13.3%)
      reported that they chewed betel quids and most of them (145/154) were men. Among
      the chewers, 33 (21.4%) indicated that they chewed it daily; all were men. Age
      distribution of the chewing behavior suggested that more young people chewed it
      at the time of the survey than had been the case in the past. The demographic
      distributions of betel quid chewing behavior were similar to the characteristics
      of tobacco smoking in Taiwan. The degree of concurrence of these two behaviors
      was very high. Nearly 90% of the subjects believed that betel quid chewing would
      cause more harm than good, or it would cause only harm, to their health.
      Discriminant analyses indicated that smoking behavior and attitude toward the
      health effect of chewing betel quids were the two most significant and meaningful
      variables in prediction of the chewing behavior. Strategies for prevention are
      recommended.

PMID- 8860145
TI  - Increased elafin expression in cystic, dysplastic and neoplastic oral tissues.
AB  - Expression of human leukocyte elastase inhibitor, elafin, otherwise known as skin
      derived antileukoproteinase inhibitor (SKALP), was investigated in normal and
      abnormal oral tissues using a specific anti-SKALP rabbit antiserum. Weak staining
      was observed in keratinizing epithelia of normal oral mucosa but not in non
      keratinizing mucosa. Increased expression was also observed in the suprabasal
      layers of dysplastic oral epithelia and in well-differentiated squamous cell
      carcinoma, but not in basal cell carcinoma. A uniform strong expression was
      observed in all supra-basal layers of odontogenic keratocyst epithelia, except in
      regions where inflammatory infiltrate was adjacent to keratocyst epithelia. In
      contrast, elafin expression in a small number of dentigerous cysts and
      ameloblastomas was more patchy. The increased levels of elafin in keratocyst
      epithelia and dysplastic tissue may be a cellular homoeostatic response to
      generate a protective barrier preventing proteolytic degradation of underlying
      elastic tissue.

PMID- 8860147
TI  - Greenspan lesion is a better term than oral "hairly" leukoplakia.

PMID- 8860148
TI  - Exit-site study methods and results.
AB  - Contrary to peritonitis, where the clinical presentation is clearly different
      from that of normal, there is a spectrum of appearances from uninfected to
      infected exit sites. This led to imprecise definitions of exit-site infection,
      difficulties in interpreting the results of various studies, and many, varied
      treatment recommendations. We have performed 565 evaluations of 61 healed exit
      sites in 56 patients. The exit and the sinus were inspected using a Zeiss prism
      loupe with 4.5x magnification for the presence, absence, intensity, and/or
      characteristics of specific attributes such as swelling, color, crust, drainage,
      granulation tissue, and epithelium in the sinus. Pictures of the external exit
      and the visible sinus tract were then drawn and photographs of the exit site and
      visible sinus tract were taken. Visual attributes discerned by loupe inspection
      were verified by review of photographs. A new classification was developed with
      six distinct categories of exit appearances: acute infection, chronic infection,
      external cuff infection, equivocal, good, and perfect. Finally, the category of
      traumatized exit was established, because trauma may result in various
      appearances. The outcomes in each category were correlated with treatment
      measures in a 5-year longitudinal study. The validity of this classification and
      its applicability to clinical practice was subjected to further investigation in
      a cross-sectional study. Forty-five patients were evaluated only once by ZJT
      using a Zeiss prism loupe and by the primary nurse, who used a handheld
      magnifier. The features were recorded and classification was made. The results of
      loupe and magnifier evaluations were then compared regarding agreement in
      discerning features. In 41 evaluations (91%) there was agreement. The new
      classification may be useful in making treatment decisions, in reporting exit
      site infection data, and in designing improved prospective, randomized studies.

PMID- 8860149
TI  - Classification of normal and diseased exit sites.

PMID- 8860150
TI  - Exit-site healing post catheter implantation.
AB  - The study goals were (1) to describe the natural healing process post peritoneal
      dialysis catheter implantation; (2) to discern factors that predispose to exit
      infection; (3) to recognize signs of early exit-site infection; and (4) to
      ascertain the influence, if any, of the healing process on subsequent peritonitis
      rates and final catheter outcomes. There were 226 evaluations of 43 exits [range
      3-6 per exit, mean 5.2 + or - 1.1 (SD)] in 41 patients. Eleven exits were in the
      parasternal area and 32 exits were in the abdomen. Exit sites and sinus tracts
      were examined weekly for 6 weeks with a magnifying loupe and macro-photographed.
      Cultures were taken from sterile saline sinus washouts, periexit smears, and
      nares. Exit sites were categorized into four types: (1) fast-healing exits had no
      drainage or minimal moisture deep inside by the third week; epidermis started to
      enter into the sinus within 2-3 weeks, progressed steadily, and covered at least
      half the visible sinus tract 4-6 weeks after implantation; (2) in slow-healing
      exits without infection, epidermis started to enter into the sinus after 3 weeks
      or progressed slowly and did not cover half the visible sinus by 5 weeks; the
      sinus might have had serous or serosanguineous, but never purulent, drainage
      persistent up to 4 weeks; (3) healing interrupted by infection initially looked
      identical to the fast-healing exit, but within 6 weeks the epidermis did not
      progress or regress, granulation tissue became soft or frankly fleshy; drainage
      increased and/or became purulent; (4) in slow-healing exits due to early
      infection, granulation tissue became soft or fleshy and/or drainage became puru
      lent by 2-3 weeks; sinus epidermization was delayed or progressed slowly, only
      after infection was appropriately treated. Compared with patients with fast
      healing exits, patients with early infected exits were more likely (although not
      significantly) to be diabetics, to have an abdominal catheter, wound hematoma,
      higher body mass index, and higher percentage of positive cultures for
      Staphylococcus aureus in nares. Early colonization of the exit was the most
      significant factor in determining the healing pattern: the later the
      colonization, the better the healing. Positive culture from either washout or
      periexit smear one week after implantation was associated with early exit
      infection, a higher peritonitis rate, and a high probability of catheter loss due
      to an exit/tunnel infection, and higher peritonitis rate; however, the time to
      the first peritonitis episode was not shorter than in the groups with later exit
      colonization. We postulate that exit infections and peritonitis rates may be
      decreased by delaying exit colonization using prophylactic antibiotics for at
      least 2 weeks after implantation and sterile exit dressing procedure for the
      entire healing time of approximately 6 weeks.

PMID- 8860151
TI  - Appearance and classification of healing peritoneal catheter exit sites.

PMID- 8860152
TI  - Recommendations for exit care.

PMID- 8860153
TI  - Recommendations for treatment of exit-site pathology.
AB  - Good local care including measures to prevent trauma keeps healthy exit sites
      free of infection. Acute infection can be cured with aggressive therapy. Chronic
      infection may progress to cuff infection, which even when treated, may progress
      to peritonitis. Cuff and tunnel infections require deroofing, cuff shaving,
      and/or catheter removal. Therapy may prolong the life of a catheter. An equivocal
      exit site requires aggressive therapy in order to achieve cure. Local care of the
      exit should include measures to prevent trauma. Should trauma occur, aggressive
      therapy that includes a systemic antibiotic should be instituted immediately.
      Aggressive therapy is particularly indicated during the healing period.
      Prophylactic antibiotics, systemic or topical, are indicated in trauma, recurrent
      infection, and may be beneficial during the healing period.

PMID- 8860154
TI  - Peritoneal catheter exit-site morphology and pathology: prevention, diagnosis,
      and treatment of exit-site infections. Case reports for independent study.

PMID- 8860155
TI  - How to monitor and report exit/tunnel infections.

PMID- 8860192
TI  - Lifetime rates of suicide attempts among subjects with bipolar and unipolar
      disorders relative to subjects with other Axis I disorders.
AB  - The lifetime rate of suicide attempts among subjects in the Epidemiologic
      Catchment Area database with bipolar disorder, unipolar disorder, and any other
      DSM-III-defined Axis I disorder were determined. The latter constituted a control
      or reference group. The lifetime rates of suicide attempts of persons in these
      diagnostic groups were 29.2%, 15.9%, and 4.2%, respectively. Multivariate
      logistic regression analysis was used to calculate the odds ratio of subjects
      within a diagnostic group having a history of a suicide attempt relative to
      subjects in a second group. The odds ratio of subjects with bipolar disorder
      having a history of a suicide attempt relative to subjects in the control group
      was 6.2 (df 1, x(2) = 5347.2, p < .0001). The odds ratio of subjects with
      unipolar disorder having a history of a suicide attempt relative to subjects in
      the control group was 3.1 (df = 1, x(2) = 4785.2, p < .0001). The odds ratio of
      subjects with bipolar disorder having a history of a suicide attempt relative to
      unipolar subjects was 2.0 (df = 1, x(2) = 697.9, p < .0001). Bipolar disorder has
      a strong relationship to a history of suicide attempts relative to unipolar
      disorder and other Axis I disorders.

PMID- 8860193
TI  - High plasma prolactin levels after long-term neuroleptic treatment.

PMID- 8860194
TI  - Impact of neuroleptic medications on continuous performance test measures in
      schizophrenia.

PMID- 8860195
TI  - Attention deficit hyperactivity disorder in a multigenerational pedigree.

PMID- 8860196
TI  - Race, IQ, and genetics.

PMID- 8860197
TI  - A case of paroxetine-induced akathisia.

PMID- 8860198
TI  - Depletion of choline acetyltransferase activity but preservation of M1 and M2
      muscarinic receptor binding sites in temporal cortex following head injury: a
      preliminary human postmortem study.
AB  - Abnormalities of cholinergic neurotransmission have been implicated in the memory
      deficits that result from head injury on the basis of results obtained from
      experimental animal models and cholinergic agonist treatment in head-injured
      survivors. The purpose of the present study was to make a preliminary
      investigation of pre- and postsynaptic markers of cholinergic transmission in
      human postmortem brain from patients who died as a result of head injury and age
      matched controls. Choline acetyltransferase activity, M1 and M2 receptor binding
      sites were assayed in the inferior temporal gyrus from 7 head-injured patients
      and 7 controls. The mean value of choline acetyltransferase activity was reduced
      by approximately 50% in the head-injured group compared to the control, although
      in 2 head-injured cases enzyme activity was similar to that of controls. In
      contrast to the reduction in choline acetyltransferase activity, there was no
      difference between the head-injured and control groups in the levels of either M1
      or M2 receptor binding. These preliminary results indicate that there is a
      significant presynaptic abnormality of cholinergic neurotransmission in
      postmortem human brain following head injury but that muscarinic receptor binding
      sites are unaltered.

PMID- 8860199
TI  - Posttraumatic hyperemia in immature, mature, and aged rats: autoradiographic
      determination of cerebral blood flow.
AB  - Clinical studies suggest that increased cerebral blood flow (CBF), or hyperemia,
      after traumatic brain injury (TBI) is commonly found in children and young
      adults, but is less often found in adults older than 40 years. However, whether
      posttraumatic cerebral hyperemia is truly an age-related phenomenon has not been
      proven. Using a model of focal percussive TBI, we hypothesized that (1) local CBF
      (ICBF) is increased by 24 after injury, and (2) the magnitude of the ICBF
      increase is age-related and is greatest in immature rats. Wistar rats that were
      immature (3.5-4.5 weeks), mature (2-3 months), and aged (14.5-15.5 months) were
      anesthetized and ventilated. TBI was produced by dropping a weight on the exposed
      right parietal cortex. LCBF was determined by [(14)C]iodoan-tipyrine
      autoradiography at 24 h posttrauma in all three age groups, at 48 h posttrauma in
      immature and mature rats, and at 7 days posttrauma in mature rats. In all age
      groups, low ICBF (<50 mL 100 g(-1) min(-1)) was present in the area of impact at
      all times studied. At 24 h, hyperemia was observed (vs. corresponding regions of
      age-matched control rats) in immature and mature rats (7/17 and 5/17 regions,
      respectively, both p < 0.05), but not in aged rats. Comparisons of ICBF between
      the three age groups revealed a hyperemic response in the peritrauma region in
      immature rats. Hyperemia persisted to 48 h in both immature and mature rats (2
      and 7 of 17 structures with increased ICBF in immature and mature rats,
      respectively, both p < .05). By 7 days posttrauma no regions of increased ICBF
      were found. Posttraumatic hyperemia appears to be an age-dependent phenomenon.
      These results suggest possible age-related differences in vasoreactivity or
      regional metabolism after TBI.

PMID- 8860200
TI  - Continuous measurement of changes in regional cerebral blood flow following
      cortical compression contusion trauma in the rat.
AB  - Laser Doppler flowmetry (LDF) was used to study acute ipsilateral and
      contralateral disturbances of regional cerebral blood flow (rCBF) in a rat model
      of cerebral cortical contusion trauma. Twelve rats were intubated and
      artificially ventilated during and after trauma. Injury was produced with a
      weight drop technique (21 g from 35 cm) allowing 1.5 mm maximum compression of
      the right parietal cortex. Stationary laser Doppler probes were used for
      continuous blood flow measurements on the ipsilateral side adjacent to the
      traumatized tissue and on the contralateral side. Within 2 min blood flow
      decreased to 60% (+/- 9%) of the pretrauma rCBF level on the ipsilateral side and
      remained at this level for at least 20 min. On the contralateral side there was
      an initial increase to 172% (+/- 27%) at 4 min. This hyperperfusion phase was
      followed by a mild hypoperfusion phase with a flow of 78% (+/- 8%) of baseline,
      lasting approximately 60 min. An attempt was made to measure rCBF++ within the
      trauma site using a removable probe. We found that probe replacement in
      traumatized (as compared to control) animals caused a baseline shift with a
      considerable variability making interpretation difficult. However, the pattern of
      rCBF change did not differ from the measurements adjacent to the injury site. We
      tentatively conclude that the posttraumatic hypoperfusion phase was similar
      within the trauma region. The observed rCBF changes following trauma are similar
      to those seen following cortical spreading depression (CSD). We propose that CSD,
      known to occur on the ipsilateral side in our model, is one of the factors
      involved in acute blood flow decreases seen following cerebral trauma.

PMID- 8860201
TI  - Reduction of the neurological deficit in mice with traumatic brain injury by
      nitric oxide synthase inhibitors.
AB  - This study investigates the effect of the NO synthase inhibitors, NG-nitro-L
      arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), on the neurological
      deficit 24 h after a moderate closed head injury in mice. Low doses of L-NAME or
      7-NI given soon after the injury significantly reduced the neurological deficit
      compared to the vehicle-treated group. L-Arginine (300 mg/kg) did not alter the
      neurological deficit, but reversed the protective effects of both L-NAME and 7-NI
      when given at the same time. Both L-NAME and 7-NI had dose-related effects. The
      neuroprotective effects of L-NAME and 7-NI occurred when the drugs were given 5,
      30, or 60 min after brain injury, but not when treatment was begun 2 h after
      brain injury, suggesting a short therapeutic window for both drugs. These results
      suggest that NO synthesis by neuronal NO synthase plays an important role in the
      early neurotoxic cascade leading to neurological deficit following traumatic
      brain injury.

PMID- 8860202
TI  - Dextrorphan reduces infarct volume, vascular injury, and brain edema after
      ischemic brain injury.
AB  - Focal cerebral ischemia confined to the cerebral cortex in the right middle
      cerebral artery (MCA) territory was induced by temporary ligation of the MCA and
      both common carotid arteries (CCAs). Reperfusion was initiated by releasing all
      three arterial occlusions after 90 min of ischemia. Infarct volume was
      morphometrically measured after triphenyltetrazolium chloride staining 24 h
      postischemia. Blood-brain barrier breakdown was assessed 4 h postischemia by
      measuring vascular permeability to fluorescein isothiocyanate-conjugated dextran
      (FITC-D), a macromolecule tracer. Ischemic brain edema was measured based on
      percent water content, 24 h postischemia. Dextrorphan (DX) 20-10 mg/kg given ip
      15 min before ischemia reduced infarct volume in a dose-dependent manner with an
      apparent U-shaped dose-response curve; best protection was observed at 30 mg/kg.
      Posttreatment at 30 min, but not 60 min, was still effective. DX (30 mg/kg, given
      15 min before ischemia) also reduced the postischemic increase in vascular
      permeability and brain edema in the right MCA cortex. Results from this study
      support the idea that NMDA receptor activation contributes to blood-brain barrier
      breakdown and brain edema after ischemic insults

PMID- 8860203
TI  - Hemoglobin potentiates excitotoxic injury in cortical cell culture.
AB  - Excessive activation of glutamate receptors may contribute to neuronal loss after
      a traumatic or ischemic central nervous system insult. Such injuries are often
      associated with hemorrhage and extravasation of hemoglobin, a prooxidant and
      putative neurotoxin. In this study, we investigated the effect of nontoxic
      concentrations of hemoglobin on the neurotoxicity of the synthetic glutamate
      receptor agonists NMDA, AMPA, and kainate in primary murine cortical cultures.
      Continuous exposure to each excitotoxin alone for 24-28 h produced concentration
      dependent neuronal death (EC(50) about 12 mu M for AMP(+)A, 50 mu M for kainate,
      and 12 mu M for NMDA). Hemoglobin 0.25-1.0 mu M consistently potentiated the
      neurotoxicity of low concentrations of AMPA and kainate, increasing neuronal loss
      by about 150% at 6 mu M AMPA and by about 90% at 30 mu M kainate. This effect was
      attenuated by the iron chelator deferoxamine and the alpha-tocopherol analogue
      trolox. Hemoglobin coexposure had less impact on slowly triggered NMDA
      neurotoxicity, significantly increasing neuronal death only at agonist
      concentrations that alone produced little or no injury. Hemoglobin pretreatment
      had no effect on the rapidly triggered excitotoxicity induced by brief exposure
      to high concentrations of NMDA. These results suggest that hemoglobin may
      contribute to neuronal loss after CNS hemorrhage by exacerbating excitotoxicity.
      At moderate levels of agonist exposure, this effect may be somewhat selective for
      the AMPA/kainate component of injury.

PMID- 8860228
TI  - Evidence for polewards forces on chromosome arms during anaphase.
AB  - We have identified new mitotic forces in crane-fly spermatocytes, separate from
      forces on the kinetochore, that propel chromosome arms in anaphase towards the
      spindle pole. In normal spermatocytes, the chromosome arms in anaphase generally
      trail the kinetochore to the pole. After ultraviolet-microbeam irradiation of a
      kinetochore spindle fibre, however, chromosome arms moved closer to the pole than
      the kinetochore. This poleward arm-movement occurred regardless of whether the
      irradiation stopped the movement of the associated chromosomes, and occurred both
      in chromosomes associated with the irradiated fibre and in chromosomes not
      associated with the irradiated fibre. Arms that moved ahead of the kinetochore
      continued to lead the kinetochore to the pole for the duration of anaphase.
      Ultraviolet-microbeam-irradiation-induced movement of arms ahead of the
      kinetochore is specific for irradiation of spindle fibres: irradiations of the
      cytoplasm outside the spindle had no effect, and irradiations of the region
      between spindle and mitochondrial sheath (that outlines the spindle) and
      irradiations of the interzonal region are much less effective than irradiations
      of spindle fibres in causing arms to move. We argue that in crane-fly
      spermatocytes forces propelling chromosome arms toward the pole are part of
      normal anaphase.

PMID- 8860229
TI  - Relative changes in F-actin during the first cell cycle: evidence for two
      distinct pools of F-actin in the sea urchin egg.
AB  - The cortical actin cytoskeleton undergoes dramatic rearrangements during
      fertilization of sea urchin eggs. To characterize these changes further, we
      quantified the relative changes in filamentous actin (F-actin) during
      fertilization and the first cell cycle in both intact eggs and in isolated
      cortices by quantitative fluorescence microscopy. The level of F-actin in the
      intact egg decreased after fertilization and continued to decrease throughout the
      first cell cycle. By 60 min after fertilization, the level of F-actin had
      decreased to 50% of the unfertilized sea urchin egg. By cytokinesis, the level of
      F-actin had decreased to 30% of the unfertilized egg. After completion of cell
      division, individual blastomeres had 10% of the F-actin in the unfertilized egg.
      In contrast, there was an increase in cortical F-actin to 370% of the level in
      the unfertilized egg after fertilization. This increase corresponded to the
      formation of microvilli. There was little change in the level of cortical F-actin
      during the first cell cycle. We draw parallels to other systems that increase the
      amount of F-actin in the Triton-insoluble cytoskeleton by recruiting actin from a
      Triton-soluble pool of F-actin.

PMID- 8860231
TI  - Actin filament translocations in sea urchin eggs.
AB  - Rhodamine (rh) phalloidin was used as a probe for actin filaments in living eggs
      and was observed using confocal microscopy. Exogenous, rh phalloidin labeled
      actin filaments were injected into eggs and were observed to translocate in the
      cytoplasm. At fertilization, filaments accumulated at the fertilization cone. Rh
      phalloidin alone, injected at concentrations that did not interfere with
      fertilization or mitosis, labeled filaments in the interior of unfertilized eggs,
      some of which translocated. At fertilization, staining increased dramatically at
      the fertilization cone and to a lesser degree around the entire cortex. At about
      9 min, many filaments appeared to detach and translocated away from the egg
      surface. This study shows that there are mechanisms that can translocate actin
      filaments within the egg cytoplasm (at approximately 0.2-0.3 mu m/sec), and
      raises the possibility that at least some of the changes in actin filament
      organization after fertilization are due to translocation of filaments.

PMID- 8860230
TI  - Plant profilins rescue the aberrant phenotype of profilin-deficient Dictyostelium
      cells.
AB  - To characterize the function of plant profilins in vivo, we expressed two pollen
      specific Zea mays (maize) profilin isoforms in profilin-minus Dictyostelium
      discoideum mutants. In maize, profilins exist as a multigene family containing 4
      or more members which are highly similar to each other but substantially less
      similar to profilins from animals and lower eukaryotes. Previously we have shown
      that D. discoideum profilin-minus cells have an aberrant phenotype due to defects
      in cell shape, cytokinesis, and development. These defects could be rescued by
      introducing the pollen-specific profilins 1 or 2 from maize using a newly
      constructed expression vector. Expression of the heterologous profilins in
      Dictyostelium clones was assayed by affinity purification of the pollen profilins
      with poly-proline agarose and by immunoblotting with a polyclonal antiserum
      raised against maize pollen profilin. In contrast to the profilin-minus mutants,
      Dictyostelium cells expressing plant profilins showed normal cell shape,
      contained less F-actin, and were able to form fruiting bodies. These data provide
      genetic evidence that maize pollen profilins, even though they are specific for a
      distinct developmental stage, share functional properties with profilin from a
      lower eukaryote and apparently act as G-actin-sequestering proteins in this
      system.

PMID- 8860232
TI  - Mitotic arrest in Ptk(2) cells induced by microinjection of a rabbit antiserum
      and affinity-purified antibodies against a 66-kDa PtK(2) cell polypeptide.
AB  - Cell division was arrested by injection of a preimmune rabbit serum, B-61, into
      PtK(2) cells during interphase and prometaphase. Identical results were obtained
      by injection of whole B-61 antiserum and of antibodies affinity-purified from the
      serum against a 66-kDa PtK(2) cell polypeptide. When injected into interphase
      cells, the antibodies arrested further development and cell division. When
      injected into prometaphase and metaphase cells, spindles shortened and poles
      moved together at a rate of 0.2-0.4 mu m/min, approximately half the rate of
      anaphase A chromosome movements in normally dividing PtK(2) cells. Chromosomes
      decondensed and cells did not reenter division. Both whole antisera and affinity
      purified antibodies stained antigens diffusely localized throughout the cytoplasm
      in dividing and interphase cells. These results suggest that the 66-kDa antigen
      is a nonspindle protein that may regulate mitotic progression in PtK(2) cells.

PMID- 8860233
TI  - Forces acting on the fission yeast anaphase spindle.
AB  - The fission yeast mitotic spindle consists of three sets of microtubules: one
      that extends between the chromosomes and the spindle pole bodies (SPBs); one that
      extends between the two SPBs forming a region of overlap; and a third, the so
      called astral microtubules, that associates laterally with the cytoplasmic face
      of the SPBs, during anaphase B. The major bundles of the latter can exist with
      equal probability in two configurations which we have termed parallel and
      convergent. Mitosis in fission yeast is characterised by an extended anaphase B
      during which the spindle elongates from 2 mu m (the diameter of the interphase
      nucleus) to about 14 mu m, spanning the entire length of the cell. Anaphase B
      spindles viewed by indirect immunofluorescence microscopy frequently appeared
      bowed but only when the astral microtubules were in the convergent orientation.
      To investigate the possible significance of this observation, we have examined
      the situation in the abnormally long spindles that are formed in cells in which
      cell length has been extended either by overexpression of the weel + gene or by
      inactivation of the cdc25 + gene. The spindles in these strains were often
      considerably longer (up to 30 mu m) than in wild type cells but, unlike the
      latter, did not extend the entire length of the cell. Bowed spindles were again
      observed but only when the astral microtubules were convergent. We discuss these
      findings in the context of the astral microtubules either exerting a pulling
      force on the poles of the anaphase B spindle, or counteracting a pushing force
      generated by sliding of anti-parallel pole to pole microtubules of the mitotic
      spindle, or both of the above.

PMID- 8860234
TI  - Human and monkey cholinergic neurons visualized in paraffin-embedded tissues by
      immunoreactivity for VAChT, the vesicular acetylcholine transporter.
AB  - The predicted C-terminal dodecapeptide of the human vesicular acetylcholine
      transporter (VAChT), deduced from the unique open reading frame of the recently
      cloned human VAChT cDNA, was conjugated through an N-terminal cysteine to keyhole
      limpet hemocyanin and used as an immunogen to generate polyclonal antihuman VAChT
      antibodies in rabbits. The distribution of the VAChT antigen in representative
      regions of the cholinergic nervous system was examined and compared to that of
      the acetylcholine biosynthetic enzyme choline acetyltransferase (ChAT), a
      specific marker for cholinergic neurons. VAChT immunoreactivity was localized in
      cell bodies of neurons in the basal forebrain and ventral horn of the spinal
      cord, regions in which major cholinergic projection systems to the cerebral
      cortex and to skeletal muscle, respectively, originate. The primate caudate
      nucleus contained numerous VAChT-positive interneurons. VAChT immunoreactivity
      was visualized in both cell bodies and extensive terminals in striatal
      interneurons, in contrast to formalin-fixed, deparaffinized sections stained for
      ChAT, in which cell bodies and fibers were stained but nerve terminals were less
      well visualized than with the VAChT antiserum. VAChT-positive nerve fibers were
      visualized in routinely immersion-fixed, paraffin-embedded human cerebral cortex,
      comparable to the density of fibers observed in perfusion-fixed Bouin's-postfixed
      monkey cerebral cortex. Extensive investment of virtually all principal ganglion
      cells of thoracic sympathetic ganglia of monkey and human with VAChT-positive
      nerve terminals was observed. VAChT-positive cell bodies, presumably
      corresponding to cholinergic sympathetic sudomotor neurons, were a significant
      fraction of the total principal cell population in monkey and human thoracic
      sympathetic ganglia.

PMID- 8860236
TI  - Three related brain nuclear receptors, NGFI-B, Nurr1, and NOR-1, as
      transcriptional activators.
AB  - Three related orphan nuclear receptors that are expressed in the brain, NGFI-B,
      Nurr1, and NOR-1, were studied to compare their function as transcriptional
      activators. NGFI-B was able to activate (in the absence of added hormone) in CV1
      cells both an NGFI-B-responsive luciferase reporter gene (containing eight copies
      of a response element for NGFI-B upstream of a basal prolactin promoter driving
      the luciferase gene, NBRE(8)-LUC), a similar thyroid hormone-receptor-responsive
      reporter gene (TRE(3)-LUC), and a reporter gene with an authentic promoter from a
      Xenopus vitellogenin gene containing two binding sites for the estrogen receptor
      (vit-LUC). NGFI-B activated NBRE(8)-LUC and TRE(3)-LUC (but not the vitLUC) with
      an amino-terminal activation domain. Nurr1 was less promiscuous as a
      transcriptional activator, activating.the NBRE(8)-LUC better than NGFI-B, but
      less than NGFI-B at the other reporter genes. NOR-1 activated only the NBRE(8)
      LUC reporter gene. These results indicate that closely related nuclear receptors
      may differentiate between response elements or promoters and that different
      activation mechanisms exist depending on the promoter. This may contribute to
      regulation of specificity of target gene expression in the brain.

PMID- 8860235
TI  - Neurotrophins and their trk receptors in cultured cells of the glial lineage and
      in white matter of the central nervous system.
AB  - Previous studies have analyzed the expression of different members of the
      neurotrophin family and their trk receptors in glial cultures composed mainly or
      exclusively of type-1 astrocytes, whereas only partial data have been published
      on other cultured glial types. In this article we compare the mRNA levels for
      neurotrophins (NGF, BDNF, NT-3, NT-4) and their high-affinity receptors (trkA,
      trkB, trkC) in cultures enriched in specific glial types, such as microglia, type
      1 astroglia, and cells of the O/2A lineage (type-2 astroglia and
      oligodendroglia). Relatively high levels of NGF mRNA (comparable to those
      observed in adult rat cerebral cortex) are present in all types of cultured glial
      cells, except for a low level of expression in cultures enriched in microglial
      cells. In contrast, BDNF mRNA is undetectable in all cultures examined. NT-3 and
      NT-4 mRNA molecules, at a level equal to that observed in adult rat cerebral
      cortex, are easily detected in type-1 astrocyte cultures, whereas their
      hybridization signals are undetectable in cells of the O/2A lineage and in
      microglial cultures. The analysis of neurotrophin receptor mRNAs confirms the
      absence of trkA mRNA, the presence of relatively high levels of trkB mRNA (70
      100% of cerebral cortex values), and low levels of trkC mRNA (10-18% of cerebral
      cortex values) in both cultured astroglial and oligodendroglial cells. Only very
      low levels of trkB and trkC mRNAs are observed in microglial cultures. Although
      cultured glial cells express mainly mRNAs encoding for the truncated form of trkB
      and trkC, a low level of mRNA encoding for the full-length catalytic form of
      these receptors is detected by the sensitive ribonuclease protection assay.

PMID- 8860237
TI  - Beta-amyloid precursor protein (APP) and APP-RNA are rapidly affected by
      glutamate in cultured neurons: selective increase of mRNAs encoding a Kunitz
      protease inhibitor domain.
AB  - Alternative splicing of beta-amyloid precursor protein (APP) RNA generates APP
      isoforms with or without a Kunitz protease inhibitor (KPI) domain. Previously, we
      showed that KPI (+) APP RNA, but not KPI (-) APP RNA, is upregulated in response
      to experimental lesions in which neurotoxicity is dependent on NMDA receptor
      activation and in Alzheimer's disease hippocampus. Recent studies by Mucke et al.
      (1995) showed that neuronal expression of human KPI (+) APP, but not KPI (-) APP,
      in transgenic mice is neuroprotective against experimental lesions. In this study
      we examined the direct effects of the excitotoxic amino acid Glu on
      alternatively, spliced APP RNAs and the corresponding protein isoforms in
      cultured rat cortical neurons. Glu treatment rapidly induced (4.5 h) KPI (+) APP
      RNA but not KPI (-) APP RNA. Induction of KPI (+) RNA preceded Glu-induced
      neuronal cell death and was partially blocked by an NMDA-receptor antagonist. In
      contrast to the RNA, cellular levels of KPI (+) APP were not changed by 4.5 h of
      Glu treatment. Instead, the cellular full-length form of the protein KPI (-) APP
      was reduced by approximately 50% after 2 h of Glu treatment and remained depleted
      after 24 h of treatment. Cellular levels of KPI (+) forms of amyloid precursor
      like protein 2 (APLP2) were not changed by Glu treatment. Our data are consistent
      with the hypothesis that sustained NMDA-receptor activation can regulate
      alternative splicing of the APP pre-mRNA in neurons.

PMID- 8860239
TI  - Isolation and characterization of the alpha-subunit of the rat rod photoreceptor
      cGMP-gated cation channel.
AB  - A combination of genomic and PCR clones has been used to derive the full-length
      coding sequence of the alpha-subunit of the rat rod photoreceptor cGMP-gated
      cation channel. The sequence encodes a protein of 683 amino acids with a
      predicted molecular weight of 79,221. The sequence shows extensive homology with
      other rod cGMP-gated channels and also with the rat olfactory cyclic nucleotide
      gated cation channel. When the full-length sequence of the rat rod channel was
      expressed in Xenopus oocytes it gave a conductance that responded to cGMP with an
      EC(50) of 42 mu M. No response to 2 mM cAMP was detected. The conductance was
      decreased in the presence of increasing concentrations of calcium. Both
      monoclonal and polyclonal antibodies were generated against a C-terminal peptide
      of the rat rod channel. On immunoblots of adult rat retinal membranes the
      antibodies recognized a band of 71 kDa, suggesting that the rat channel may
      undergo proteolytic cleavage in the retina, as has previously been found for the
      bovine rod channel. Immunocytochemical labeling of adult rat retinal sections
      detected prominent labeling over the rod photoreceptor outer segments with both
      monoclonal and polyclonal antibodies.

PMID- 8860273
TI  - Pipe smoking in the United States, 1965-1991: prevalence and attributable
      mortality.
AB  - BACKGROUND: National pipe-smoking prevalence data have rarely been reported, and
      mortality associated with pipe smoking has not been estimated. METHODS: We
      analyzed National Health Interview Survey data from 1965, 1966, 1970, 1987, and
      1991 to estimate adult pipe-smoking prevalence in the United States. For each of
      these years, we estimated pipe smoking-attributable mortality from chronic
      obstructive pulmonary disease and cancers of the oral cavity, larynx, esophagus,
      and lung. RESULTS: From 1965 to 1991, the prevalence of current pipe smoking for
      men declined 12.1 percentage points (from 14.1% to 2.0%) while pipe smoking
      remained very uncommon among women. By 1991, pipe smoking was a behavior found
      primarily among men age 45 years or older. Most men who smoked pipes also used
      other tobacco products, especially cigarettes. About 830 deaths (range 720-2,495)
      in 1965 and 1,095 deaths (range 655-2,820) in 1991 were attributable to pipe
      smoking. CONCLUSIONS: If current trends continue, pipe smoking will become
      extremely rare in the United States by the year 2000. Reasons for the decline in
      pipe smoking may include the lack of appeal of pipe smoking to women and
      adolescents or the increasingly unfavorable image of smoking behavior in general.
      Prevention and cessation efforts need to be directed against all forms of
      tobacco, including smokeless tobacco use, cigar smoking, and pipe smoking.

PMID- 8860274
TI  - Editors' requests of peer reviewers: a study and a proposal.
AB  - BACKGROUND: Despite the pivotal role of peer review in the scientific process,
      there has never been a formal study of the way in which reviewers' opinions are
      elicited. This article describes such a study and makes recommendations for a
      more standardized approach to the peer review process. We hope, through this
      publication and related efforts, to encourage such a process in Preventive
      Medicine and in other journals. METHOD: The study population included the top 100
      journals (as rated by the 1989 Institute for Scientific Information citation
      frequency index). Only journals with primarily U.S.-based editorial offices are
      included (n = 73). Participants provided their reviewer forms, cover letters for
      reviewers, and instructions for reviewers that were used routinely. All data were
      collected in February 1992. RESULTS: The response rate was 97.3%. Journals varied
      substantially in many of their reviewer requests. While 96% of journals asked
      reviewers to recommend acceptance or rejection, only 72% asked reviewers to
      assess manuscripts' novelty, 69% requested assessments of clarity, and only 51%
      asked for assessments of the reasonableness of manuscripts' conclusions.
      Similarly, only 46% of journals reminded reviewers that manuscripts were
      confidential documents, 51% provided a separate cover letter, and 25% provided
      extensive (>1 full page) reviewer instructions. CONCLUSIONS: While review
      uniformity is not requisite, differences between review protocols may not be a
      function of specific journals' needs, but of some journals' excluding important
      review components from explicit mention. Based in part on the Council of Biology
      Editors' recommendations, standard components of reviews and of instructions for
      reviewers are suggested. If editors' expectations were more explicit, reviewers'
      comments could better serve editorial needs.

PMID- 8860238
TI  - Reserpine- and tetrabenazine-sensitive transport of (3)H-histamine by the
      neuronal isoform of the vesicular monoamine transporter.
AB  - The transport of (3)H-histamine by the endocrine-specific (VMAT1) and neuronal
      (VMAT2) isoforms of the vesicular monoamine transporter has been evaluated in
      digitonin-permeabilized fibroblasts transfected with either VMAT1 or VMAT2.
      Transport of (3)H-histamine by both VMAT1 and VMAT2 was reserpine-sensitive but
      only transport by VMAT2 was inhibited by tetrabenazine. Maximal equilibrated
      levels of (3)H-histamine accumulation by VMAT2 (K(m) 300 mu M) were approximately
      three times greater than that mediated by VMAT1 when using a subsaturating
      concentration of exogenous (3)H-histamine (50 mu M). The expression of VMAT2 in
      histaminergic neurons in the rat brain was examined with polyclonal antipeptide
      antibodies specific for VMAT1 or VMAT2. VMAT2-positive and tyrosine hydroxylase
      negative immunoreactive cell bodies were localized to the ventral part of the
      posterior hypothalamus in the region of the mamillary nuclei. The transport
      properties of VMAT2 and the distribution of VMAT2 in cell bodies in the
      tuberomammillary nucleus of the posterior hypothalamus reported here and the
      apparent absence of VMAT1 and VMAT2 in tissue mast cells support previous
      findings of reserpine-sensitive and reserpine-resistant pools of histamine in
      brain and peripheral tissues.

PMID- 8860275
TI  - AIDS-related attitudes and risk behaviors: a survey of a random sample of
      California heterosexuals.
AB  - BACKGROUND: This paper describes the results of an AIDS knowledge, attitudes, and
      behaviors survey of a random sample of heterosexual California adults. METHODS:
      The study was conducted from August 1990 until February 1991 and consisted of
      telephone interviews conducted in English and Spanish, with a household
      probability sample of 3,545 California adults, undersampling those age 44 and
      older. RESULTS: Approximately one-third of the sample believed that HIV/AIDS is
      contracted by donating blood, and 20% believed the infection could result from
      insect bites. Tolerance toward HIV-infected persons was highest among young,
      male, white, employed individuals with higher levels of education and income.
      Twenty-seven percent of males and 14% of females were categorized as high risk
      based on the presence of at least 1 of 7 risk factors. High-risk respondents
      tended to be male, young, employed, never married, U.S. born, and English
      speaking. Compared to low-risk respondents, they were less likely to use condoms
      and more likely to use alcohol and drugs in conjunction with sex. Most common
      sources of AIDS information were television, newspapers, and magazines.
      CONCLUSIONS: More strenuous efforts are needed to reach young adults, especially
      those beyond college age, with AIDS prevention messages. Creative messages via
      popular media venues should be explored.

PMID- 8860276
TI  - Use of screening mammography and clinical breast examinations among black,
      Hispanic, and white women.
AB  - BACKGROUND: Breast cancer screening can be an effective tool in the early
      detection of breast cancer but remains underused by women in the United States.
      METHODS: We analyzed data from 22,657 women (2,068 black women, 707 Hispanic
      women, and 19,882 white women) who participated in the 1990 Behavioral Risk
      Factor Surveillance state-based telephone survey. Using the recommended
      guidelines of the American Cancer Society for breast cancer screening, we
      examined utilization rates by demographic and selected variables, stratified by
      ethnic groups. RESULTS: Of the women included in the analysis, 47% of both black
      and Hispanic women and 50% of white women reported having had a recent mammogram,
      and 68% of black women, 59% of Hispanic women, and 66% of white women reported
      having had a recent clinical breast examination (CBE). Important predictors of
      the use of breast cancer screening procedures for each group were having had a
      routine examination in the past year, having seen an obstetrician or gynecologist
      or specialist during the last routine examination, and more than a high school
      education. CONCLUSIONS: Many women are not having mammography and CBEs. Efforts
      to increase screening must focus on encouraging providers to use CBEs as a
      screening tool and to recommend mammography. Strategies should be developed to
      increase the use of these procedures among women, particularly those of low
      income and low education levels.

PMID- 8860277
TI  - Two sequential randomized trials of community participation to recruit women for
      mammographic screening.
AB  - BACKGROUND: If mammographic screening is to reduce mortality from breast cancer,
      it is essential that a high proportion of the target population attend for
      screening. In order to achieve this, effective recruitment strategies are needed.
      This paper reports two trials of recruitment strategies for mammographic
      screening involving eight communities in rural New South Wales (NSW), Australia.
      METHODS: Each trial involved two matched pairs of towns in the Hunter Valley
      region of NSW. Towns were randomly allocated to intervention, receiving either
      mass media promotion or community participation in Trial 1 and community
      participation or family physician involvement in Trial 2. RESULTS: In Trial 1,
      significantly higher attendance rates were observed in the two towns that
      received the community participation intervention compared with their matched
      media promotion towns (63% vs 34%, P < 0.001 and 51% vs 34%, P < 0.01). In Trial
      2, a significantly higher attendance rate was observed in one town that received
      the family physician involvement intervention compared with its matched town
      which received the community participation intervention (68% vs 51%, P < 0.01).
      There was no significant difference in attendance in the other pair of towns (68%
      vs 58%, P = 0.11). CONCLUSIONS: Both community participation and family
      practitioner involvement are more promising strategies for the promotion of
      attendance at mammographic screening facilities than media promotion alone.

PMID- 8860278
TI  - Reduction of coronary heart disease risk factors in the German cardiovascular
      prevention study.
AB  - BACKGROUND: In six regions of former West Germany, a community-oriented
      prevention program for coronary heart disease (CHD) was conducted over a 7-year
      period. METHODS: In the intervention regions, CHD prevention activities were
      performed with special emphasis on healthy nutrition, increased physical
      activity, and reduction of smoking, hypertension, and hypercholesterolemia. The
      impact of these activities on CHD risk factor trends was observed in three
      independent samples of the intervention regions. Three independent representative
      samples of the total West German population were used as a reference. Linear
      regression models with interaction terms to represent the intervention effects
      were used to test for differences in risk factor trends. RESULTS: In the pooled
      intervention regions, a net reduction in mean values of systolic (-2.0%) and
      diastolic (-2.0%) blood pressure, total serum cholesterol (-1.8%), as well as the
      percentage of smokers (-6.7%) was observed compared with the nationwide trend.
      From the major CHD risk factors, only body mass index was not influenced in the
      intervention population. CONCLUSIONS: The community-oriented German
      Cardiovascular Prevention program can effectively be used to reduce CHD risk
      factors in a broad population.

PMID- 8860279
TI  - Reducing cancer risk among Native American adolescents.
AB  - BACKGROUND: This article discusses the development, implementation, and
      preliminary testing of an intervention to reduce cancer risks through tobacco use
      prevention and dietary modification among Native American youth in the
      Northeastern United States. METHODS: The intervention outcome study includes a
      research design and outcome measurement instruments. In collaboration with Native
      American communities, reservations, and organizations in the Northeastern United
      States, implementation of the design quantifies the separate and combined effects
      of a tobacco use prevention and a dietary modification intervention. RESULTS:
      Native American youths in the tobacco prevention intervention and in the combined
      tobacco and dietary intervention increased their knowledge of tobacco facts and
      their awareness of the motives of tobacco advertising, and showed higher ratings
      for an ability to resist peer pressure and to refuse offers of tobacco use
      between pretest and posttest. Youths in the combined intervention were
      significantly less apt to report smoking of any kind. Youths in the tobacco use
      prevention-only condition reported significantly less smoking than their
      counterparts in the dietary modification-only condition and control condition on
      4 of 8 measurement items. As for dietary variables, pretest to posttest
      measurement scores showed that, after receiving the curriculum, youths in the
      dietary modification intervention and in the combined intervention improved their
      knowledge of the health implications of consuming dietary fat, fiber, fruits, and
      vegetables. Youths in the dietary modification and combined intervention also
      improved their scores of knowledge related to cancer risk-reducing nutritional
      practices, cultural dietary habits, and healthy food choices available for Native
      American cultures. Youths in the dietary modification-only condition report
      significantly increasing their consumption of complex carbohydrates and
      significantly decreasing their fat intake between pretest and posttest occasions.
      CONCLUSIONS: Data from this longitudinal study suggest the value of the FACETS
      curriculum for helping Native American youth reduce their risks for cancer
      associated with tobacco use and dietary preference and consumption patterns. In
      particular, results indicate the enhanced effects of the combined tobacco use
      prevention and dietary modification intervention for preventing tobacco use and
      for improving youths' knowledge and attitudes with regard to tobacco use and
      diet. Further, the study demonstrates the value of collaborating with Native
      American organizations to design a cancer risk-reducing curriculum and to
      implement tests of that curriculum.

PMID- 8860280
TI  - Pap smear screening in a health maintenance organization: 1986-1990.
AB  - BACKGROUND: To assess Pap smear utilization and compliance with screening
      recommendations, a study was conducted in a large midwestern HMO where cost is
      not a barrier to care. The purpose of the study was to examine rates of screening
      by age, identify the proportion of abnormal cytologic findings, and determine
      screening incidence for women with a diagnosis of cervical cancer. METHOD:
      Computerized records on screening frequency over a 5-year interval were examined
      for 23,649 consecutively enrolled women ages 18-70. In addition, medical records
      were examined for patients with a cervical cancer diagnosis (n = 32). RESULTS:
      Eighty-five percent of the women had at least one Pap smear within the 5-year
      duration. Nearly half (47%) obtained four to five tests, 30% obtained two or
      three tests, and 14% were screened only once during the 5 years. Percentages were
      similar across all age groups. Cytopathology reports indicated 95% of tests as
      normal, 4% as low-grade squamous intraepithelial lesions (SIL), <1% as high-grade
      squamous intraepithelial lesions, and 0.02% as suspected malignancy. Younger
      women were more likely to evidence SIL; older women were somewhat more likely to
      have carcinoma. For women with a cancer diagnosis, 63% had not been screened the
      previous year and 34% had no screening recorded for the prior 3 years. Twenty-two
      percent had no record of screening within the past 5 years compared with 8.5% of
      the total group. CONCLUSIONS: In HMOs with prepayment, one would hypothesize that
      patients would obtain more regular preventive screening of all types, yet women
      at highest risk seemed less likely to obtain Pap smear screening. This group is
      not fully understood and probably represents the best opportunity to reduce
      morbidity, mortality, and expense from preventable cervical neoplasias.

PMID- 8860281
TI  - Attitudes toward risk factor behavior of relatives of cancer patients.
AB  - BACKGROUND: Targeted health promotion requires an identifiable subpopulation
      which is accessible, at increased risk, receptive to input, and receptive to
      change. Relatives of recently diagnosed cancer patients may meet these criteria
      and have not previously been investigated as recipients of preventive education
      regarding smoking and diet. METHODS: This study investigates these factors,
      beliefs regarding perceived susceptibility to cancer, and attitudes toward
      behavior change in 101 relatives of 50 patients with smoking-related cancers,
      breast cancer, and other diet-related cancers. Congruence of attitudes between
      patients and relatives, another possible factor in changing health behaviors,
      also was assessed. RESULTS: Access to relatives of patients was very high, as was
      their willingness to discuss these issues (99% of relatives contacted
      participated in the survey). Relatives' ratings of relevant risk factors were
      generally higher than those of patients; ratings of their own vulnerability were
      moderate. Within diagnostic groups, there was high concordance of belief between
      patients and relatives for certain types of risk, such as heredity for breast
      cancer (r = 0.81) and smoking for smoking-related cancers (r = 0.52), but not for
      dietary factors. CONCLUSIONS: The high level of access suggests that relatives
      may be receptive to discussing issues of behavior risk and change. They are at
      least as aware as patients of cancer risk factors. Spontaneous behavior change
      was very low. They may therefore be good candidates for targeted health promotion
      regarding cancer risk.

PMID- 8860282
TI  - Perceived susceptibility to and knowledge of malignant melanoma: screening
      participants vs the general population.
AB  - BACKGROUND: The incidence of and mortality from melanoma are increasing and no
      effective treatment for disseminated disease exists. Studies of factors
      influencing participation in prevention and early detection of melanoma are
      therefore warranted. In the present study, participants in public melanoma
      screening were compared with a sample of the Swedish population with respect to
      concern for nevi, perceived risk for melanoma, knowledge about melanoma, and
      sources of information. Gender differences were studied. METHOD: Consecutive
      participants in public melanoma screening (Participants) received questionnaires
      at registration for skin examination; 235 (96%) responded. Questionnaires were
      distributed by mail to a random sample of the Swedish population (Public); 1,070
      (63%) responded. RESULTS: Participants were more concerned about nevi, and a
      higher proportion had previously consulted physicians for suspected lesions
      compared with the Public. Participants were better informed in terms of the
      number of sources of information and knowledge of melanoma and risk factors.
      There were no differences regarding perceived risk and there was a mixed picture
      concerning knowledge of sun effects and sun protection. Gender differences were
      found for perceived susceptibility to, knowledge of, and number of sources of
      information about melanoma, favoring women. CONCLUSION: The preventive aspects of
      screening as well as the good prognosis of melanoma detected early should be
      stressed in invitations to skin cancer screening. New approaches for reaching men
      are warranted.

PMID- 8860283
TI  - Cesarean section rates by type of maternity unit and level of obstetric care: an
      area-based study in central Italy.
AB  - BACKGROUND: The rate of cesarean section in the Lazio region of Italy is one of
      the highest in the Western world, 26.5%. In order to evaluate the effects of
      nonmedical factors on cesarean section, we examined its relationship to the
      characteristics of maternity units in the region. METHODS: We collected data from
      the birth certificates of 91,557 infants born to women residing in Lazio in 1988
      1989 and classified all maternity units in the region by method of financing
      (public, semiprivate with arrangements with the national health service, and
      completely private) and level of obstetric care (unclassified and levels I,II,
      and III). The rates of cesarean section were examined for primiparous and
      multiparous women, taking into account birthweight, gestational age, fetal
      presentation, maternal age, and day of delivery. RESULTS: The adjusted odds ratio
      for cesarean section (with public units of level I taken as reference) was 1.06
      (primiparous) and 1.22 (multiparous) for semiprivate maternity units and 1.59
      (primiparous) and 1.52 (multiparous) for private units; it increased to 1.59
      (primiparous) and 1.61 (multiparous) for unclassified semiprivate units and to
      2.06 (primiparous) and 1.87 (multiparous) for unclassified private units.
      CONCLUSIONS: The rate of cesarean section was associated in the Lazio region with
      private payment for hospital care and with inadequate level of obstetric care.
      The latter factor is of particular concern and should be investigated elsewhere.

PMID- 8860284
TI  - Promoting worksite smoking control policies and actions: the Community
      Intervention Trial for Smoking Cessation (COMMIT) experience. The COMMIT Research
      Group.
AB  - BACKGROUND: As an important aspect of the COMMIT trial, worksite smoking-control
      consultations and supports were provided to employers in 11 diverse, moderate
      sized communities. After a 4-year intervention period (1989-1992), impacts on
      worksite policies, support resources for smokers, and employee perceptions were
      assessed in these communities and in 11 matched Comparison communities. METHODS:
      Data from two surveys are reported here. In each of the 22 COMMIT communities, a
      sample of worksites within each of four size strata were surveyed to determine
      worksite policies, activities, and resources regarding smoking. Data from
      employees were obtained from independent community-wide surveys of community
      residents. RESULTS: Overall, 44% of the worksites surveyed reported having smoke
      free policies, with no differences between Intervention and Comparison
      communities. Thirty-seven percent of Intervention community work-sites reported
      offering smoking cessation resources or assistance for employees during the
      period of the study, compared to 31% of Comparison community worksites (P =
      0.04). Employees in Intervention communities, relative to those in Comparison
      communities, reported greater awareness of stop-smoking resources, but equivalent
      increases in worksite smoking bans. CONCLUSION: Although the level of worksite
      smoking-cessation activities was higher in Intervention than in Comparison
      communities, there remains a substantial need to increase the level of such
      activities and to integrate such activities with restrictive smoking policies.

PMID- 8860286
TI  - The influence of gender and socioeconomic factors on Hispanic/white differences
      in body mass index.
AB  - BACKGROUND AND METHODS: This article examines the effects of gender and
      socioeconomic factors on ethnic differences in body mass index (BMI) using a
      matched-pairs design of 688 pairs of Hispanics (principally Mexican American) and
      whites. Subjects, ages 25-74, were drawn from five population-based surveys
      conducted from 1979 to 1990 in four northern California cities. RESULTS: Hispanic
      women and men both had significantly higher BMI levels than the white women and
      men with whom they were matched (P < 0.001). These ethnic differences persisted
      across every level of education for both women and men, with the magnitude of the
      difference ranging from 0.9 BMI units (between the most educated Hispanic and
      white men) to 2.9 BMI units (between the least educated Hispanic and white
      women). The highest prevalence of overweight was among the least educated
      Hispanic women (61.1%) and Hispanic men (48.4%). The higher BMI levels of
      Hispanic women and men relative to their white counterparts were not explained by
      age, gender, education, city of residence, time of survey, or language spoken in
      a multiple regression model. Hispanic women and men both reported higher desired
      body weight (height standardized) than white women and men, indicating a possible
      contribution of cultural factors to the ethnic differences in overweight.
      CONCLUSIONS: These findings provide insight into the greater prevalence of
      overweight in Hispanic relative to white populations as well as guidance for
      weight-loss interventions tailored to low socioeconomic groups.

PMID- 8860285
TI  - Determinants of intention to quit smoking among Dutch employees: the influence of
      the social environment.
AB  - BACKGROUND: This study examines the influence of the social environment in
      worksites on employees' intention to quit smoking by applying the attitude-social
      influence-efficacy model. METHODS: Regression analyses were conducted with 509
      smoking employees from eight Dutch worksites. Variables of interest were
      attitudes toward smoking, perceived social pressure to quit, perceived smoking
      behavior of others, self-efficacy, demographics, smoking history variables,
      company type, and smoking tolerance. RESULTS: Attitude, social pressure from
      people out-side the worksetting (partner, children), and self-efficacy explained
      23% of the variance for intention. Past behavior increased the adjusted R2 from
      0.23 to 0.29. Social influences in the worksite were unrelated to employees'
      intention to quit smoking. CONCLUSIONS: It was concluded that, in Dutch work
      sites, social influences stemming from people at work have less influence on
      employees' intention to quit smoking than other important people outside the work
      situation. Implications for smoking control strategies in worksites are briefly
      discussed.

PMID- 8860287
TI  - Determinants of fat and fiber consumption in American rural energy workers.
AB  - BACKGROUND: The objective of this study was to gain insight into the determinants
      of dietary fat and fiber consumption in American rural energy workers. Main
      determinants in this study were knowledge, efficacy expectations, and outcome
      expectations. The determinants will be ordered in a model, assuming that efficacy
      and outcome expectations predict intention. METHODS: The study consisted of a
      cross-sectional survey. The questionnaires on food behavior and the determinants
      of fat and fiber consumption were administered to the subjects at the same time.
      Models of determinants of fat and fiber consumption were derived from the
      correlation and regression analyses. RESULTS: There were 211 questionnaires
      analyzed. The scales were shown to be valid and reliable. In the models of
      determinants of fat and fiber consumption the following determinants were
      generated: gender, education, knowledge, interest, efficacy expectations, outcome
      expectations, and intention. In this study efficacy expectations were important
      to determine fat and fiber consumption. CONCLUSIONS: Efficacy expectations can be
      considered an important variable of an intervention program aiming at the
      decrease of fat consumption and at the increase of fiber consumption in rural
      energy workers.

PMID- 8860288
TI  - Reasons for delay in breast cancer diagnosis.
AB  - BACKGROUND: A study of system delay, the time between the initial medical
      consultation and the establishment of a diagnosis, in breast cancer patients
      revealed that almost 40% of women reported delays of at least 4 weeks. The
      objective of this study was to explore the reasons for these prolonged intervals
      between initial medical consultation and establishment of a diagnosis. METHODS: A
      total of 367 female breast cancer patients from the National Cancer Institute's
      Black/White Cancer Survival Study were studied. Medical systems involved in the
      diagnosis and treatment of these women included hospital outpatient and emergency
      room, private clinic, public clinic, private doctor, and health maintenance
      organization. RESULTS: In about 25% of the cases, the delay was attributed by the
      woman to the patient herself, and the most common reason she gave was that she
      felt that the problem was not important. In about 45% of the cases, the provider
      and the health care system were said to be responsible for the delay through
      difficulties in scheduling or physician inaction, while in another 17% both the
      patient and the system were responsible. CONCLUSIONS: This study looked at the
      issue of how the behaviors of women and their providers contribute to the timing
      of breast cancer diagnosis. It is one of the only studies to examine the woman's
      role in delay. It is clear from this study that additional work is needed to look
      at this question. However, the results of this study suggest that efforts must be
      made to reduce the time needed to get an appointment with a physician or a
      diagnostic test, as well as to educate physicians and the women themselves
      regarding the importance of breast symptoms and the value of prompt evaluation,
      diagnosis, and treatment.

PMID- 8860302
TI  - Occurrence of immunoreactive activin/inhibin beta(B) in gonadotrophs,
      thyrotrophs, and somatotrophs of the Xenopus pituitary.
AB  - An antibody against the Xenopus activin/inhibin beta(B) subunit (94-107) was
      raised in a rabbit. Using this antibody, the distribution of activin/inhibin
      beta(B) immunoreactivity in the pituitary of adult X. laevis was studied. Beta(B)
      immunoreactivity was detected in gonadotrophs, thyrotrophs, and somatotrophs
      under light microscopy. Electron microscopy revealed that a beta(B)
      immunoreactive substance exists in LH, TSH, and GH granules, in contrast to
      findings in the rat and goldfish. These results indicate that the expression of
      activin/inhibin beta(B) in pituitary cells is not consistent among vertebrate
      species.

PMID- 8860303
TI  - Cloning and sequencing of an equine insulin-like growth factor I cDNA and its
      expression in fetal and adult tissues.
AB  - A cDNA for equine insulin-like growth factor I (IGF I) has been isolated by
      reverse transcriptase-polymerase chain reaction and subsequently sequenced. The
      sequenced fragment contained 465 bp including the coding regions for the signal
      peptide, the entire mature protein, and 4 amino acids into the E-peptide. Like
      its human counterpart, the mature equine IGF I peptide contains 70 amino acids
      and was 100% homologous between horse and man. The 49-amino-acid signal peptide
      had the threonine in position 26 of the human signal peptide substituted by
      isoleucine. The nucleotide homology across the entire clone was 96.3% between
      horse and man and 91.6% between horse and rat. The isolated cDNA hybridized to
      the same transcripts in fetal and adult tissues.

PMID- 8860304
TI  - Occurrence of somatostatin and insulin immunoreactivities in the stomach of sea
      bass (Dicentrarchus labrax L.): light and electron microscopic studies.
AB  - Somatostatin (SST)- and insulin (INS)-immunoreactive (ir) cells were identified
      in the gut of sea bass (Dicentrarchus labrax) by immunofluorescence double
      staining and peroxidase-antiperoxidase (PAP) techniques for light microscopy and
      by immunogold method for electron microscopy using antisera to mammalian and fish
      peptides. SST-14 and SST-25 immunoreactivities coexisted in cells mainly located
      among the mucous neck cells of the gastric glands. Preabsorption controls showed
      that some SST-25- and, possibly, some SST-14-like peptides appeared in these
      cells. Immunoreactivity to fish INS, but not to mammalian INS (mINS) or insulin
      like growth factor I (mIGF-I), was observed in all the SST-ir cells. The
      preabsorption controls suggest a cross-reaction of the fish INS antisera with SST
      containing or type I cells. These cells displayed ovoid or round secretory
      granules with fibrous, medium electron-dense or homogeneous osmiophilic
      materials. Some gastric cells (type II) with round secretory granules of variable
      electron density, which were gold immunolabeled with bonito INS but not with
      mINS, mIGF-I, or SST antisera, were also found. INS-related peptide in type II
      cells of the sea bass stomach is suggested.

PMID- 8860305
TI  - Immunocytochemical localization of the Pit-1 protein in the pituitary of the
      rainbow trout (Oncorhynchus mykiss).
AB  - Pit-1 is a pituitary-specific transcription factor responsible for activating the
      growth hormone (GH) gene family. The localization of Pit-1 protein in the
      pituitary of rainbow trout was studied by immunocytochemical analysis. Fish Pit-1
      was found to be extensively localized in the nuclei of cells in the proximal pars
      distalis (PPD), rostral pars distalis (RPD), and pars intermedia (PI). Sagittal
      sections were immunocytochemically double stained with antibodies against Pit-1,
      GH, prolactin (PRL), and somatolactin (SL). The results showed that Pit-1 protein
      was present in the GH-containing cells of the PPD, the PRL-containing cells of
      the RPD, and the SL-containing cells of the PI.

PMID- 8860306
TI  - VIP-like immunoreactive cells in the kidney of goldfish (Carassius auratus).
AB  - By immunohistochemistry VIP-like immunoreactive cells were observed in the second
      segment of some renal proximal tubules of Carassius auratus. Immunoreactivity
      displayed a granular appearance all over the cells. VIP-like immunoreactive cells
      showed a shape of an over-turned flask whose globe-like part looks like the
      tubular lumen. No immunoreactive material was observed in other tracts of the
      nephron and in the interstitial cells. The presence of VIP-like immunoreactive
      cells is discussed in relation to their possible function.

PMID- 8860307
TI  - Gonadotropins beta-GtHI and beta-GtHII from the gilthead seabream, Sparus aurata.
AB  - Full-length cDNA sequences encoding the beta-subunits of the gonadotrophins GtHI
      and GtHII were isolated, cloned, and sequenced from a single gilthead seabream
      (Sparus aurata) pituitary using RACE PCR. Beta-GtHI and beta-GtHII degenerate PCR
      primers were designed according to regions of high amino acid sequence homology
      between the chum salmon and the bonito beta-GtHI or beta-GtHII. DNA sequence
      analysis of the cloned PCR products confirmed the presence of the predicted
      complete coding region as well as 5' and 3' untranslated sequences. The deduced
      amino acid sequences of beta-GtHI and beta-GtHII from the gilthead seabream were
      compared to GtH sequences from a number of teleosts. Seabream beta-GtHI shows the
      highest homology to the bonito beta-GtHI (76%) and the striped bass (74%), while
      seabream beta-GtHII is 98% homologous to the yellow fin porgy, 87% homologous to
      the bonito, and 93% homologous to the striped bass beta-GtHII. Northern blot
      analysis showed the transcripts of the gilthead seabream beta-GtHI and beta-GtHII
      to be about 700 and 740 bases, respectively. During the spawning season, beta
      GtHI is expressed at higher levels in males than in females while beta-GtHII is
      expressed at similar levels in both sexes.

PMID- 8860308
TI  - 3,5,3'-Triiodo-L-thyronine and L-thyroxine uptake into red blood cells of rainbow
      trout, Oncorhynchus mykiss.
AB  - Uptake of the thyroid hormones (TH) 3,5,3'-triiodo-L-thyronine (T3) and L
      thyroxine (T4) by trout red blood cells (RBC) was studied by incubating washed
      RBC in a balanced salts medium containing glucose and [125I]TH at the fish
      acclimation temperature of 12 degrees. RBC were separated from the medium by
      centrifugation through silicone oil and glycine buffer (pH 10.5). Maximal
      [125I]T3 uptake occurred by 10-15 min, but not by 60 min for [125I]T4. First
      order uptake was measured at 30 sec for T3 and at 90 sec for T4. Total T4 uptake
      was enhanced 15-fold from pH 8 to 6 and was affected most below pH 7.2; total T3
      uptake was maximal between pH 6.4 and 7.0, but was relatively insensitive to pH.
      At 0.2 nM, nonsaturable uptake of T3 exceeded that of T4 3- to 6-fold, accounting
      for 3% (T3) and 50% (T4) of total uptake. Saturable TH uptake was described by
      Michaelis-Menten kinetics. The saturable transport system for T3 had an apparent
      K(t) (carrier affinity) of 70-119 nM and J(max) (maximal uptake velocity) of 540
      1116 pmol . 10(6) cells(-1) . min(-1). A saturable system was also found for T4,
      with an apparent K(t) of 99 pM-1.1 nM and J(max) of 8-77 fmol . 10(6) cells(-1) .
      min(-1). Saturable uptake of both TH depended on temperature. Activation energies
      for the nonsaturable component were 48 (T4) and 64 (T3) KJ . mol(-1) over the
      range 0-21 degrees. Activation energies for the saturable components were 52 KJ .
      mol(-1) (T4, 0-21 degrees), 52 KJ . mol(-1) (T3, 0-10 degrees), and 3 KJ . mol(
      1) (T3, 10-21 degrees). During a 16-month study saturable and nonsaturable uptake
      of both TH increased, probably due to fish age. We conclude that in trout RBC,
      rapid T3 uptake by a pH- and temperature-sensitive saturable carrier greatly
      exceeds T4 uptake. The rate of T3 uptake exceeds by 100- to 1000-fold that of
      mammals and amphibia, and in contrast to those taxa some saturable T4 uptake also
      occurs.

PMID- 8860309
TI  - Developmental profile of plasma inhibin and gonadotropins from hatch to sexual
      maturity in male and female chickens.
AB  - The posthatch profiles of plasma immunoreactive inhibin and gonadotrophins (FSH
      and LH) were examined in male and female chickens. Blood samples were collected
      and hormones were measured by radioimmunoassay at biweekly intervals from Week 1
      through Week 19 (Week 21 in females) posthatch. Immunoreactive inhibin was
      elevated (P < 0.01) in males between Weeks 7 and 15. In contrast, immunoreactive
      inhibin was significantly elevated (P < 0.001) in females at 17 and 19 weeks
      compared to earlier time points. There was no significant difference in FSH level
      between males and females. Both sexes showed a significant (P < 0.01) rise in FSH
      during development. Males had significantly higher levels of LH compared to
      females. While there was no change in LH throughout 19 weeks in females, plasma
      LH was significantly elevated in males at 7, 11, 13, and 15 weeks. Results
      suggest that a negative relationship between inhibin and FSH may be established
      in females, in contrast to males, at the onset of puberty.

PMID- 8860310
TI  - CCK-X receptors in the endothermic mako shark (Isurus oxyrinchus).
AB  - By mapping the distribution of cholecystokinin (CCK) receptor types onto an
      established phylogenetic hypothesis of vertebrate relationships, we tested two
      hypothesis about the evolution of CCK receptors: (1) A single CCK receptor type,
      CCK-X, is the ancestral receptor, while CCK-A and CCK-B receptors represent
      derived receptor types; (2) the evolution of two separate CCK receptors is
      functionally related to the evolution of endothermy. Specifically, we localized
      and characterized 125I-CCK-binding sites in the gut and brain of mako shark
      (Isurus oxyrinchus), a warm-blooded chondrichthyean fish. Competitive inhibition
      studies of 125I-CCK binding showed that the CCK receptor in the mako shark brain,
      gallbladder, pyloric stomach, and intestine binds sulfated CCK-8 and sulfated
      gastrin-17 (gastrin-17-II) with much higher affinity (K(i) ranging from 0.05 to
      2.02 nM) than unsulfated gastrin-17 (gastrin-17-I, K(i) ranging from 4.63 to
      62.17 nM). These results indicate that the mako shark expresses a single CCK-X
      receptor in all tissues. Additional competitive inhibition studies showed that
      the mako CCK-X receptor has very low affinities for the following nonpeptide
      agonist and antagonists: A71623, L364,718, A57696, A65186.72, Cam-1481, and SR
      27897B (specific for some mammalian CCK-A receptors) and L365,260 and CI-988
      (specific for some mammalian CCK-B receptors), confirming the pharmacological
      differences between the CCK-X receptor and the CCK-A and -B receptors. Based on
      the mapped phylogenetic distribution of CCK receptor types, we conclude that CCK
      X is the ancestral receptor type and that two receptor types, e.g. CCK-A and CCK
      B, are not part of the suite of characters necessary for evolution of endothermy
      in fishes.

PMID- 8860311
TI  - A preliminary investigation of the effects of vasoactive intestinal peptide on
      secretion from the lingual salt glands of Crocodylus porosus.
AB  - Vasoactive intestinal peptide (VIP)-like immunoreactivity was demonstrated in the
      lingual salt glands of the estuarine crocodile, Crocodylus porosus. Varicose
      fibers showing VIP-like immunoreactivity ramified the salt glands, forming a
      dense network around the basal region of the exocrine cells. Secretions from the
      lingual salt glands were monitored in hatchling C. porosus. Spontaneous secretory
      activity was variable, ranging from 0.3 to 5.3 micromol Na 100 g(-0.7) bm hr(-1)
      (bm, body mass). Administration of a 100-microl bolus of 0.9% NaCl, via a
      cannulated femoral vein, did not affect the spontaneous secretory rate. However,
      injection of 100 pmol porcine VIP resulted in a massive increase in secretory
      activity, reaching a maximum of 58.2 micromol of Na 100 g(-0.7) bm hr(-1). The
      presence of VIP-like immunoreactivity and the positive secretory effect of
      administered VIP indicate a potential action of VIP on salt gland activity.

PMID- 8860312
TI  - A comparative analysis of somatolactin-related immunoreactivity in the
      pituitaries of four neopterygian fishes and one chondrostean fish: an
      immunohistochemical study.
AB  - An antiserum to cod somatolactin (SL) was used for immunohistochemical screening
      for the pars intermedia of two teleosts (Oreochromis mossambicus and Gymothorax
      meleagris), two holostean fishes (Lepisosteus osseus and Amia calva), and a
      chondrostean fish (Acipenser fulvescens) for SL-immunopositive (SL-IR) cells. As
      expected, a subset of the epithelial cells in the pars intermedia of O.
      mossambicus (tilapia) was immunopositive for SL, and the remainder of the
      epithelial cells was immunopositive for alpha-MSH-specific antiserum (alpha-MSH
      IR). SL-IR was not detected in any of the epithelial cells in the pars intermedia
      of the moray eel G. meleagris. To determine whether SL-IR could be detected in
      nonteleost fishes, immunohistochemical analyses were done on the pituitaries of
      two holostean fishes and one chondrostean fish. In the pars intermedia of the
      gar, L. osseus, a subset of cells was immunopositive for alpha-MSH only. However,
      in the pars intermedia of the bowfin, A. calva, all of the epithelial cells
      indicated the presence of both SL and alpha-MSH. Finally, no SL-positive cells
      were detected in the pars intermedia of the sturgeon, A. fulvescens.

PMID- 8860313
TI  - Role of arachidonic acid and calmodulin in mediating dopamine D1- and GnRH
      stimulated growth hormone release in goldfish pituitary cells.
AB  - In goldfish, growth hormone (GH) release is stimulated by dopamine via D1
      receptors and cAMP-dependent mechanisms and by gonadotropin-releasing hormone
      (GnRH) through a protein kinase C (PKC) pathway; in addition, both D1 and GnRH
      actions require extracellular Ca2+. In this study, the involvement of arachidonic
      acid (AA) and calmodulin (CaM) in mediating the GH responses to D1 and GnRH
      stimulation was examined using primary cultures of dispersed goldfish pituitary
      cells. In 2-hr static incubation experiments, the phospholipase A2 inhibitor
      bromophenacylbromide (BPB; 50 microM) decreased the GH responses to the D1
      agonist SKF38393 (1 microM), the adenylate cyclase activator forskolin (10
      microM), and the cAMP analog 8Br-cAMP (1 mM), but not the responses to salmon
      (s)GnRH (100 nM), chicken (c)GnRH-II (100 nM), and AA (50 microM). Similarly, the
      phospholipase A2 inhibitor quinacrine (50 microM) and an inhibitor of AA
      metabolism, nordihydroguaiaretic acid (NDGA; 50 microM), reduced the GH responses
      to SKF38393, forskolin, and 8Br-cAMP. The response to the dopamine agonist
      apomorphine (1 microM) was also decreased by NDGA. The GH responses to AA did not
      add to those of forskolin or SKF38393, but were additive to responses to sGnRH
      and the PKC activator tetradecanoyl phorbol acetate (TPA; 100 nM). In perifusion
      experiments, treatment with BPB reduced the acute GH response to 1 microM
      SKF38393, 10 microM forskolin, or 1 mM 8Br-cAMP. Taken together, these results
      suggest that mobilization and metabolism of AA mediate both acute and prolonged
      GH responses to D1, but not GnRH. The involvement of AA probably occurs distal to
      D1-induced cAMP generation. Two-hour static incubation with 10 nM to 10 microM
      KN62, a CaM-dependent kinase II inhibitor, decreased the GH response to 100 nM
      sGnRH or cGnRH-II. KN62 (1 microM) similarly decreased the GH response to 1 mu M
      SKF38393, 10 microM forskolin, 1 mM 8Br-cAMP, or 100 nM TPA. In perifusion
      studies, KN62 (1 microM) also reduced the acute GH response to 5 min pulses of
      100 nM sGnRH, 100 nM cGnRH-II, or 1 microM SKF38393. These results indicate that
      CaM mediates the acute, as well as the prolonged, GH responses to GnRH and
      dopamine. The involvement of CaM likely occurs distal to cAMP and PKC.

PMID- 8860314
TI  - Seasonal variation of LH, sex steroids, body mass, molt, display, and laying in
      two subspecies of Houbara bustard, Chlamydotis undulata macqueenii and
      Chlamydotis undulata undulata, housed in outdoor cages under natural conditions.
AB  - Subspecies of the Houbara bustard are resident in North Africa (Chlamydotis
      undulata undulata) or are partial latitudinal migrants in Asia (Chlamydotis
      undulata macqueenii). Houbara breed in arid or semiarid zones, and the
      reproductive biology of wild Houbara is largely unknown. Body mass, molt,
      courtship display, laying, and plasma concentrations of LH, testosterone, and
      progesterone were measured in captive-bred birds of both subspecies, housed in
      outdoor cages under natural conditions, over a period of 1 year and 6 months, at
      Taif, Saudi Arabia (21 degrees 15' N). Captive Houbara bustards show a seasonal
      breeding pattern with a laying period from January to July. Males began
      displaying well in advance of any eggs laid and display long after the
      termination of laying. In females, gonadal activity and molt were mutually
      exclusive; however, in males, slight overlap between sexual display and molt was
      observed. In females, seasonal variation of LH and progesterone was synchronous
      with laying activity. In males both testosterone and LH plasma concentrations
      were highest in January (testosterone approximately 8 ng/ml; LH approximately 3
      ng/ml) at the beginning display period. This could correspond, in the wild, to
      the establishment of territories. Levels dropped significantly before the females
      started laying but stayed at an intermediate level throughout the breeding season
      (testosterone approximately 3 ng/ml; LH approximately 1.5 ng/ml). In the middle
      of August, during molt, and following heavy rainfall, LH and testosterone peaked
      (testosterone approximately 2.3 ng/ml; LH approximately 1.8 ng/ml), suggesting a
      possible impact of rainfall on Houbara gonadal activity. Houbara stopped laying
      before the maximum ambient temperature reached 32 degrees, indicating that high
      temperature could be a factor terminating laying activity. No major differences
      were found between the two subspecies in the timing or duration of the
      reproductive period; only the annual variation of the body mass varied slightly
      between the subspecies.

PMID- 8860315
TI  - Immunohistochemical and ultrastructural evidence of adrenal chromaffin cell
      subtypes in sea bass Dicentrarchus labrax (L.).
AB  - Histology demonstrated chromaffin cells in the head kidney and opisthonephros of
      the sea bass. Immunohistochemistry showed the catecholamine-synthesizing enzymes
      tyrosine hydroxylase and dopamine beta-hydroxylase in these cells.
      Phenlethanolamine N-methyltransferase was detected in a fraction of the
      chromaffin cells in the head kidney (59%) and in the opisthonephros (54%).
      Distinct noradrenaline- and adrenaline-synthesizing cells are therefore
      suggested. Ultrastructural analysis confirmed the existence of two main
      chromaffin cell types, distinguished by different types of the secretory
      granules. Cells that contain vesicles with a round, electron-dense core were
      interpreted as noradrenaline cells, while cells with electron-lucent vesicles
      were identified as adrenaline cells. The ultrastructure of these chromaffin cell
      subtypes does not differ in the head kidney and opisthonephros. A minor
      population of chromaffin cells was identified, which typically show smaller
      vesicles with an electron-dense core. This population may account for a limited
      number of not fully differentiated chromaffin cells.

PMID- 8860316
TI  - Circadian regulation of a daily rhythm of release of prothoracicotropic hormone
      from the brain retrocerebral complex of Rhodnius prolixus (hemiptera) during
      larval-adult development.
AB  - A daily rhythm of release of prothoracicotropic hormone (PTTH) has been reported
      throughout most of larval-adult development in Rhodnius prolixus. PTTH released
      by explanted brain-retrocerebral complexes was quantified using an in vitro
      bioassay in which the PTTH released into the incubation medium was assayed by its
      ability to stimulate ecdysteroid synthesis in arrhythmic prothoracic glands
      (PGs). The present article employs this assay to reveal that the daily rhythm of
      PTTH release is under circadian control. The rhythm free-runs in both continuous
      darkness (DD) and continuous light (LL) with a period length close to 24 hr,
      which is temperature compensated. The rhythm appears to damp out more rapidly in
      LL than in DD. It is argued that the circadian clock regulating PTTH release is
      in the brain and is entrained by extra-retinal photoreception. It is suggested
      that this "PTTH clock" is coupled in vivo to the clock previously described in
      the PGs that regulates rhythmic ecdysteroid synthesis by the circadian rhythm of
      release of PTTH. This coupling appears to be tight, since the rhythm of PTTH
      release retains close synchrony with the rhythm of ecdysteroid synthesis under
      both DD and LL. It is concluded that these two coupled clocks comprise a
      multioscillator system that drives the rhythms in ecdysteroid synthesis and the
      hemolymph ecdysteroid titer and consequently imposes temporal order on
      ecdysteroid-dependent developmental events.

PMID- 8860317
TI  - Mechanisms of action of free arachidonic acid on ovarian steroid production in
      the goldfish.
AB  - This study explores the mechanisms by which free arachidonic acid (AA) affects
      ovarian steroidogenesis by full-grown prematurational follicles of the goldfish
      in vitro. AA (6-400 microM) stimulated testosterone production and this action
      was mediated by prostaglandin E2 (PGE2). The steroidogenic actions of AA and the
      corresponding increase in the production of PGE2 were blocked by inhibitors of
      the cyclooxygenase pathway (indomethacin, ETYA). Exogenous PGE2 (20-2000 ng/ml)
      also stimulated steroid production. In the presence of human chorionic
      gonadotropin (hCG), AA had differential effects. AA potentiated the steroidogenic
      actions of low dosages of hCG (0.1 IU/ml), while with maximal gonadotropin (1-10
      IU/ml) stimulation a high concentration of AA (400 microM) attenuated steroid
      production in spite of elevated PGE2 synthesis, nor did it affect the PGE2
      production obtained with AA-treated follicles. The steroidogenic induction by AA
      via PGE2 was mediated in part by Ca2+ since the calcium channel blocker
      nifedipine (25 microM) inhibited stimulated steroid production by both AA and
      PGE2. The conversion of AA to PGE2 does not require Ca2+ since PGE2 production by
      AA-treated follicles was not affected by nifedipine. However, treatment with the
      calcium ionophore A23187 (1 microM) potentiated the stimulatory actions of AA on
      steroid and prostaglandin production. The phosphodiesterase inhibitor 3-isobutyl
      1-methylxanthine (1 mM) potentiated the stimulatory actions of AA on testosterone
      production but had no effect on the conversion of AA to PGE2. The steroidogenic
      actions of AA and PGE2 involve both transcription and translation since
      stimulated steroidogenesis was inhibited by actinomycin D and and cycloheximide
      (1-10 micrograms/ml). The conversion of AA to PGE2 was also blocked by these
      inhibitors. These results underscore the importance of AA and PGE2 in the
      regulation of ovarian steroidogenesis in the goldfish.

PMID- 8860318
TI  - Release of alpha-subunit of glycoprotein hormones from the bullfrog pituitary:
      possible effect of alpha-subunit on prolactin cell function.
AB  - On the basis of our previous finding that prolactin (PRL) cells of the bullfrog
      (Rana catesbeiana) contain immunoreactive alpha-subunit of pituitary glycoprotein
      hormones, experiments were conducted to see whether the immunoreactive alpha
      subunit is released from PRL cells. Cell immunoblot analysis revealed that
      approximately 10% of cells that released immunoreactive PRL also released
      immunoreactive alpha-subunit. Western blot analysis of the culture media revealed
      that a considerable amount of the free form of alpha-subunit was released from
      the dispersed anterior pituitary cells. Moreover, it was found that addition of
      alpha-subunit to the culture medium enhanced PRL release. The results raise the
      possibility that alpha-subunit secreted by PRL cells acts as an autocrine and/or
      paracrine factor.

PMID- 8860319
TI  - Ontogeny of immunoreactive steroidogenic proteins (adrenodoxin and cytochrome p
      450(21)) in the interrenals of the teleost Lates calcarifer.
AB  - Antisera against bovine adrenodoxin and cytochrome P-450(21) (steroid 21
      hydroxylase) cross-reacted with the interrenal cells of the adult Asian seabass
      (Lates calcarifer); the cells were arranged as cords, two cells thick, in the
      headkidney. During larval development, cells immunoreactive for adrenodoxin were
      first observed 1 day posthatching (dph); immunoreactivity for cytochrome P
      450(21) was first detected at 1.5 dph. Initially, the interrenal cells occurred
      as a mass in each headkidney, which only became identifiable histologically at 5
      dph. The number of interrenal cells increased with age, becoming associated with
      the cardinal veins at 14 dph. The present study thus indicates that the
      posthatching rise in cortisol may originate from the nascent interrenal tissue.

PMID- 8860320
TI  - The intersection of risk assessment and neurobehavioral toxicity.
AB  - Neurobehavioral toxicology is now established as a core discipline of the
      environmental health sciences. Despite its recognized scientific prowess,
      stemming from its deep roots in psychology and neuroscience and its acknowledged
      successes, it faces additional demands and challenges. The latter, in fact, are a
      product of its achievements because success at one level leads to new and higher
      expectations. Now the discipline is counted upon to provide more definitive and
      extensive risk assessments than in the past. These new demands are the basis for
      the appraisals presented in the SGOMSEC 11 workshop. They extend beyond what
      would be offered in a primer of methodology. Instead, these appraisals are framed
      as issues into which what are usually construed as methodologies have been
      embedded.

PMID- 8860321
TI  - The assessment of neurobehavioral toxicity: SGOMSEC joint report.
AB  - Exposure to neurobehavioral toxicants is a problem of international scope.
      Although many different procedures are available for the assessment of human
      behavioral function, performance tests are displacing traditional diagnostic
      tests for ascertaining the consequences of exposure to neurotoxic chemicals.
      Performance testing includes variables such as attention and concentration,
      sensory function, motor control, spatial relations, visuomotor coordination,
      memory, and affect. Special tests have also been devised for evaluating child
      development. One of the salient needs in these efforts is the construction of
      databases allowing access to normative data.

PMID- 8860322
TI  - Animal behavioral methods in neurotoxicity assessment: SGOMSEC joint report.

PMID- 8860323
TI  - Lessons for neurotoxicology from selected model compounds: SGOMSEC joint report.
AB  - The ability to identify potential neurotoxicants depends upon the characteristics
      of our test instruments. The neurotoxic properties of lead, methylmercury,
      polychlorinated biphenyls, and organic solvents would all have been detected at
      some dose level by tests in current use, provided that the doses were high enough
      and administered at an appropriate time such as during gestation. The adequacy of
      animal studies, particularly rodent studies, to predict intake levels at which
      human health can be protected is disappointing, however. It is unlikely that the
      use of advanced behavioral methodology would alleviate the apparent lack of
      sensitivity of the rodent model for many agents.

PMID- 8860354
TI  - How to measure and reduce the burden of zoster-associated pain.
AB  - Several parameters of shingles' pain can be measured and each provides meaningful
      information. Generally, the more comprehensive the assessment the better, but
      there are significant difficulties in measuring the duration of post-herpetic
      neuralgia (PHN). Patients with herpes zoster usually feel pain as a continuum
      and, although acute pain and PHN have different qualities and pathophysiologies,
      we lack the sophistication to determine when PHN commences. Use of an arbitrarily
      defined starting point is meaningless for the patient and may introduce
      statistical bias (particularly if acute pain and PHN are divided by the point of
      rash healing). Thus, measurement of the pain as a continuum ('zoster-associated
      pain') is advocated. We also need to decide what degree of pain intensity is
      meaningful and whether complete cessation of pain or loss of pain (or only
      'moderate/severe' pain) for a finite period is a better assessment. This approach
      to pain measurement was recently adopted in a meta-analysis of the placebo
      controlled trials of oral aciclovir in herpes zoster. When 'time to complete
      cessation of all pain' was assessed, the hazard ratio was 2.13 in favour of
      aciclovir, with a 95% confidence interval (CI) of 1.42 to 3.19. For 'time to
      complete cessation of moderate/severe pain' the hazard ratio was 1.46 (95% CI;
      1.11, 1.93); for 'time to first pain-free period' it was 1.31 (95% CI; 1.08,
      1.60). These results indicate that aciclovir significantly speeds pain resolution
      in shingles.

PMID- 8860324
TI  - Risk assessment for neurobehavioral toxicity: SGOMSEC joint report.
AB  - Behavioral end points for neurotoxicity risk assessment have been developed and
      examined over the past three decades. They are now ready to move from simple
      qualitative guidelines, such as exemplified by reference doses, to more
      quantitative models, such as benchmark doses, based on dose-response information.
      Risk assessors, confronted by a wider array of methodologies and data than in the
      past, should be offered guidance in interpretation because now they have to deal
      with unaccustomed questions and problems. These include reversibility,
      susceptible populations, multiple end points, and the details of dose-response
      and dose-effect distributions.

PMID- 8860356
TI  - The clinical relevance of different laboratory tests in CMV diagnosis.
AB  - The array of diagnostic tools now available allows not only precise serological
      determination of past exposure to cytomegalovirus (CMV) infections but also
      identification of CMV components in blood during viraemia--predictive of CMV
      disease. Sensitive and rapid identification of CMV components from infected
      organs from biopsies and body fluids, such as cerebrospinal fluid and
      bronchoalveolar lavage fluid, is also possible. The polymerase chain reaction
      (PCR) has become a highly sensitive and specific diagnostic tool that now also
      can he applied in a quantitative or semiquantitative manner. Non-PCR methods,
      which amplify the signal rather than DNA itself, are also available as
      quantitative tests. The antigenaemia assay was the first quantitative measure of
      CMV load during viraemia. It is useful in the surveillance of CMV in transplant
      patients as well as for drug efficacy monitoring, and is the method of choice in
      many laboratories. The use of modern diagnostic tools and subsequent treatment
      with an appropriate antiviral drug should reduce the number of lethal CMV cases
      to a minimum.

PMID- 8860355
TI  - Cytomegalovirus infections in transplant patients.
AB  - Cytomegalovirus (CMV) infections are a major problem in transplant recipients,
      although recent advances in diagnosis, prevention and therapy have reduced the
      risk of CMV disease. To illustrate these advances, the risks of CMV disease and
      subsequent death were analyzed in 482 consecutive bone marrow transplant (BMT)
      patients transplanted between 1975 and 1994. No CMV-seronegative patient with
      seronegative donor marrow developed disease. Among the remaining 384 patients,
      the risk for CMV disease was reduced from 13.0% in patients transplanted between
      1975 and 1985 to 2.2% in those transplanted between 1991 and 1994 (p = 0.06). The
      corresponding risks for death due to CMV disease were reduced from 13.0% to 0% (p
      = 0.002). Significant factors in multivariate analysis for the reduction of death
      from CMV disease were acute graft-versus-host disease and pre-emptive therapy
      based on rapid diagnosis with polymerase chain reaction. These data are discussed
      in relation to previously published results in BMT and solid organ transplant
      patients.

PMID- 8860357
TI  - Clinical and immunological considerations in Epstein-Barr virus-associated
      diseases.
AB  - Despite the fact that nucleoside analogues, such as aciclovir and ganciclovir,
      and DNA-polymerase inhibitors, such as foscarnet, have a proven antiviral effect
      on oropharyngeal-Epstein-Barr virus (EBV) replication, they have been unable to
      show any effect on the severity or duration of infectious mononucleosis (IM), a
      condition for which there is currently no established treatment. Clinical
      symptoms may be due to an EBV-induced polyclonal humoral, as well as cellular,
      immunoreactivity with limited pathology caused by viral replication itself.
      However, despite an extensive immune response, 90% of tested IM patients (n = 36)
      had a spontaneous outgrowth of in vivo EBV-infected B-lymphocytes at onset of
      disease, indicating lack of specific EBV-restricted cellular cytotoxicity at this
      time. Establishment of an EBV-specific T-lymphocyte response occurred 90-180 days
      after onset of disease (human leukocyte antigen-restricted cytotoxicity against
      EBV-infected B-cells). Thus, development of a specific cytotoxic response was a
      gradual and slow process. Assessment of cytokine pattern, at the single cell
      level, was performed by immunocytochemical technique and by enzyme-linked
      immunosorbent assay. This revealed an increased production of interleukin (IL)-2,
      interferon (IFN)-gamma, IL-6 and tumour necrosis factor (TNF) beta in all IM
      patients. Those with disseminated disease were characterized by lack of IFN-gamma
      production. This loss was selective since in vitro stimulation with superantigen,
      such as streptococcal pyrogenic exotoxin A, induced a normal response. These
      patients lacked signs of EBV-specific T-cell cytotoxicity in vitro. Treatment
      with intravenous or subcutaneous IFN-gamma, 1.5 MU every second day, in
      combination with intravenous immunoglobulin G (0.5 g/kg three times per week) and
      oral aciclovir, 800 mg 5 times daily, has shown promising results in some
      patients. Cytokine production in tonsil tissue in 4 patients with fulminant IM
      and respiratory tract obstruction showed a concomitant expression of IL-2, IFN
      gamma, IL-6, TNF beta, transforming growth factor (TGF) beta 1-3, granulocyte
      colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-4
      IL-1alpha, IL-beta and TNF alpha. The number of IL-2, IFN-gamma, IL-6 and TNF
      beta producing cells was significantly higher compared to tonsil tissue obtained
      from children with tonsillar hypertrophy. Thus, IM is associated with extensive
      local cytokine production. It is suggested that this extensive cytokine
      production is closely involved in the pathology of IM and that patients with
      atypical IM have a dysregulation in the cytokine network. However, the mechanism
      by which EBV-infected B-lymphocytes triggers this cytokine cascade is still
      unknown. These findings show the need for evaluation of patients with
      immunodeficiency and EBV-induced lymphoproliferative disorders and perhaps the
      introduction of new immunoregulatory treatment strategies.

PMID- 8860358
TI  - Diagnosis of Epstein-Barr virus-related diseases.
AB  - Epstein-Barr virus (EBV) is present, as both latent and replicating virus, in
      most healthy individuals, and disturbance of the normal host-virus balance may
      cause a variety of diseases. A number of diagnostic tools can he used, depending
      upon the particular condition investigated, however, serology is the best method
      for diagnosis of primary EBV infections. In approximately 85% of cases of
      mononucleosis, the primary EBV infection can he diagnosed by an assay for
      heterophile antibodies. The presence of immunoglobulin G (IgG) and IgM to
      antigens from the replicative cycle of the virus, in combination with absence of
      antibodies to the EBV nuclear antigens (EBNA 1-6), is a diagnostic for a primary
      EBV infection. Serological tests for elevated IgA levels to various EBV antigens
      have been used to screen for EBV-associated nasopharyngeal carcinoma. In those
      with AIDS with EBV-associated lymphomas of the brain, EBV genomes can always be
      detected with polymerase chain reaction on cerebrospinal fluid. Epstein-Barr
      virus involvement in tumours, other than those of the brain and solid organs, can
      be verified by in situ demonstration of EBV-DNA or by immunocytochemical
      techniques for viral antigens.

PMID- 8860378
TI  - New rapid microbiological diagnostic techniques.
AB  - OBJECTIVE: To briefly and critically review the role of new, rapid techniques,
      especially PCR, in the diagnosis of infectious diseases. METHODOLOGY: Review of
      the literature. RESULTS: New diagnostic techniques show great promise but many
      techniques are still in their infancy and the relative roles of the various
      methods remain uncertain. CONCLUSIONS: It seems likely that different techniques
      will continue to be useful in a number of different contexts. No one technique is
      likely to become 'diagnostically dominant' in the foreseeable future.

PMID- 8860379
TI  - Growth hormone therapy for 3 years: the OZGROW experience.
AB  - OBJECTIVE: To examine the growth response over 3 years of growth hormone
      deficient (GHD) and non-GHD children who have received growth hormone (GH) in
      Australia. METHODOLOGY: A retrospective study of a group of patients (1362
      children) who commenced GH prior to 1 September 1990. Data were collected at 12
      growth centres located in major cities throughout Australia. The data were
      transferred after informed consent to the national OZGROW database located at the
      Royal Alexandra Hospital for Children, Sydney, NSW. Of the 1362 children, 898 had
      received 3 years or more GH therapy and were eligible for this analysis. This
      cohort was then categorized by diagnosis. Growth response was assessed using
      height standard deviation score, estimated mature height, growth velocity (GV),
      GH dose and bone age (years). RESULTS: For children who completed 3 years
      therapy, the baseline characteristics among diagnostic groups were similar with
      mean height standard deviation score (SDS) less than -3 SDS (except for the
      malignancy group) and mean GV ranging from 3.5 to 4.4cm/year. The GV during the
      first year improved in all groups (7.7-9.4cm/year)followed by an attenuated
      response during the second and third years of therapy. After 3 years GH therapy
      the GHD group with peak levels <10 mU/L demonstrated the greatest change in
      estimated mature height and height SDS. The GHD group with peak levels between >
      or = 10 but <2OmU/L had a growth response similar to the non-GHD children for all
      outcome parameters. Change in bone age ranged from 3.1 to 3.8 years with no
      differences being noted between the diagnostic groups, nor consistently with
      pubertal status. CONCLUSIONS: Australian GH guidelines have targeted very short
      children when compared to other series. This large cohort of non-GHD children has
      demonstrated short-term benefits of GH therapy; however, the long-term benefit
      remains unclear until these children reach final adult height.

PMID- 8860380
TI  - An Angelman syndrome clinic: report on 24 patients.
AB  - OBJECTIVE: Angelman syndrome (AS) is a rare congenital neurodevelopmental
      disorder with complex genetic aetiology. Diagnosis may be difficult and there is
      severe life-long disability. An AS clinic was commenced in Sydney, Australia, in
      1993 with the aim of gathering information about the natural history of AS,
      management issues and parental concerns. METHODOLOGY: Patients were referred from
      metropolitan Sydney, rural New South Wales and interstate. A questionnaire,
      history, physical examination and diagnostic tests were undertaken. RESULTS: In
      the first year, 24 patients with AS were assessed. There were 11 males and 13
      females, whose ages ranged from 3 to 30 years. The mean age of diagnosis was 12.8
      years. The diagnosis was made by neurologists in four cases, by clinical
      geneticists in three cases, by paediatricians in two cases and 15 cases were
      diagnosed at the AS clinic. A clear history of epilepsy was obtained in 19 (79%)
      and in 15 of these patients the age of onset was during the first 4 years of
      life. An EEG had been performed in 21 patients, and in two the EEG was reported
      as normal. Fifteen of the patients (62.5%) could walk independently and in this
      cohort there was a significant sex difference in walking: 10/11 males compared to
      5/13 females (P > 0.01). Five patients (21%) were in full-time permanent care.
      Genetic testing with appropriate DNA probes from chromosome 15 (q11-13), complete
      in 20 families, showed deletion in 12 patients (60%),uniparental disomy in 1(5%)
      and no detectable abnormality in 7 (35%). CONCLUSIONS: The diagnosis of AS should
      be considered in any patient with severe developmental disability particularly if
      there is a movement disorder and lack of speech. The control of epilepsy is a
      major management problem. Further research is needed to establish the frequency
      and type of seizures, the response to anticonvulsants and to determine if
      improvement can be expected with age. The mobility of patients should be assessed
      regularly, to determine the most appropriate options for intervention.

PMID- 8860381
TI  - The social and educational outcome of a cohort of rural children in relation to
      the racial and socio-economic groupings of their parents.
AB  - OBJECTIVE: To evaluate the outcome after a generation of extra health and
      educational intervention among children whose antenatal and perinatal
      characteristics appeared influenced by racial origin and socio-economic status.
      METHODOLOGY: Sixty-five of an original cohort of 103 children born in Cunnamulla,
      Queensland, 1974-75, remained in the area allowing educational and social
      outcomes to be assessed: 40 were Aboriginal, 25 were children of unemployed
      Caucasians and 38 were children of employed Caucasians. The criteria for a
      successful outcome on leaving school were progression to further education or
      finding paid employment. RESULTS: Fifty-three of the children who had left school
      were assessed (the remaining 12 were still at school). Only four of the 30
      assessed Aborigines had successful outcomes compared with 10 of the 13 employed
      Caucasians and three of the 10 unemployed Caucasians. Gender influenced success,
      with females under-represented such that among the 23 Aboriginal and unemployed
      Caucasian girls only one had a successful outcome; 13 of these 23 girls were
      pregnant before finishing secondary education. CONCLUSIONS: The educational and
      social success of Aborigines is poor compared with the children of employed
      Caucasians. Outcomes for children of unemployed Caucasians are similar to those
      of Aborigines, suggesting failure of a range of government and community
      intervention programmes.

PMID- 8860382
TI  - Weight-for-age and weight-for-height references for Hong Kong children from birth
      to 18 years.
AB  - OBJECTIVE: Childhood obesity is an emerging problem in Asia. Sequential
      monitoring of the growth of an individual can detect a change in body fatness,
      provided there are ethnically appropriate growth references. METHODOLOGY: A
      territory wide cross-sectional growth survey of Hong Kong on 24709 individuals
      from the age of newborn to 18 years was performed in 1993. Weight-for-age and
      weight-for-height percentile charts were prepared separately for boys and girls.
      RESULTS: There was an average increase of 8.5 kg and 5.1 kg in the 18 year old
      boys and girls, respectively, compared to those surveyed 30 years ago. The
      percentile curves between 6 and 18 years were similar to those of Singapore.
      Weight-for-height percentile curves were close to those of America in the
      prepubertal years. CONCLUSIONS: These Hong Kong growth standards for weight-for
      age and weight-for-height are important tools for the assessment of nutritional
      status of an individual and for monitoring changes in nutritional status of the
      population.

PMID- 8860383
TI  - The management of acute abdominal pain in children.
AB  - OBJECTIVE: Acute abdominal pain is a common problem in childhood, and
      appendicitis is frequently diagnosed by general practitioners and doctors working
      in emergency departments. The objective of the present report was to determine
      the frequency of appendicitis in a group of children with acute abdominal pain
      presenting to the emergency department of a general hospital, as well as
      attempting to analyse the manner in which these patients were managed.
      METHODOLOGY: The initial assessment in hospital (by resident hospital staff) of
      the study group of patients was analysed and their subsequent clinical progress
      documented. RESULTS: The present report shows that the vast majority of children
      with acute abdominal pain do not have appendicitis and that appendicitis is
      significantly over-diagnosed by junior hospital doctors. CONCLUSIONS:
      Appendicitis is a clinical diagnosis, best made by an experienced member of the
      paediatric surgical team. Frequent review, with a minimum of investigations,
      provides the best means of making a rational decision regarding surgery.

PMID- 8860384
TI  - Pathophysiology of overheating in a piglet model: findings compared with sudden
      infant death syndrome.
AB  - OBJECTIVE: To examine the nature of hyperthermia-induced pathophysiological
      changes in an animal model including effects on lung compliance. METHODOLOGY:
      Piglets were randomly assigned to heated or non-heated groups. Heated animals
      were warmed to 4 degrees C above normal body temperature while sedated and
      breathing spontaneously. Cardiorespiratory variables were recorded serially and
      haematological assessments and blood cultures taken at 0 and 6 h. After 6 h the
      animals were killed and a limited postmortem was performed. Control animals had
      all procedures without heating. RESULTS: Heated piglets developed tachycardia,
      hypotension and a metabolic acidosis in addition to tachypnoea, hypocapnic
      alkalosis and a neutrophil leucocytosis. Rectal temperature after death fell at
      the same rate in both groups. Lung histology revealed an excess of lung
      haemorrhage and alveolar oedema in the heated group. No significant group
      differences in dynamic lung compliance were demonstrated. CONCLUSIONS: The
      pathological changes that occur during hyperthermia are non-specific but not
      incompatible with those found in sudden infant death syndrome. There was no
      confirmation of the thesis that hyperthermia causes death by altering lung
      compliance.

PMID- 8860385
TI  - Prevalence and aetiology of neurological impairment in extremely low birthweight
      infants.
AB  - OBJECTIVE: To determine the prevalence and perinatal predictors of cerebral
      palsy, intellectual impairment, visual impairment and deafness in a cohort of
      extremely low birthweight (ELBW) infants at two years of age. METHODOLOGY: The
      study population comprised 199 of the 224 (89%) ELBW infants managed at the
      Mater's Mothers Hospital, Brisbane, between July 1977 and February 1990 and who
      survived to two years. The prevalence of cerebral palsy, intellectual impairment,
      blindness and deafness was measured by clinical,psychometric and audiological
      assessment and the association with 24 risk factors examined. RESULTS: Cerebral
      palsy occurred in 20 children (10%). Risk of cerebral palsy was associated with
      ventricular dilatation, intraventricular haemorrhage, necrotizing enterocolitis
      and multiple birth, though only ventricular dilatation (OR 4.41; 95% CI 1.32
      14.8) remained significant in the adjusted analysis. Intellectual impairment
      occurred in 20 children (10%) and was independently associated with ventricular
      dilatation (OR 15.0; 95% CI 2.2-102.8), ventilation F(i)(2) > 80% (OR 3.4; 95% CI
      1.01-11.5), vaginal delivery (OR 3.5; 95% Cl 1.09-11.4) and male sex (OR 6.1; 95%
      Cl 1.67-22.3). No perinatal predictor was statistically associated with risk of
      deafness. Retinopathy of prematurity (OR 36.9; 95% Cl 2.8-495.5) was associated
      with risk of later visual impairment. CONCLUSIONS: Intellectual impairment was
      associated with a broad range of perinatal variables. Cerebral palsy was
      associated with fewer variables, all of which were also associated with
      intellectual impairment. Neurologic injury was associated with male sex and
      multiple birth, which are not biological insults themselves, but may be markers
      of susceptibility to injury.

PMID- 8860386
TI  - An evaluation of 1994 school entry immunization certificates on the Central Coast
      of New South Wales.
AB  - OBJECTIVE: To evaluate school entry immunization certificates and document the
      immunization status of children enrolled during 1994 in kindergartens on the NSW
      Central Coast. METHODOLOGY: Immunization certificates and non-statutory
      documentation of immunization for school entry presented by parents were
      evaluated during visits to 68 NSW Central Coast schools in May and June 1994.
      RESULTS: Immunization information for 3741 kindergarten enrollments was reviewed.
      Of these enrollments, 79% presented immunization certificates of which 10% were
      incomplete, 14% presented non-statutory documentation and 7% had no certificate
      or non-statutory documentation. It was considered that 19% of children were
      incompletely immunized; 8% of certificates presented were incorrectly completed.
      CONCLUSIONS: The study found that about 80% of Central Coast school entrants were
      fully immunized. Reliance on immunization certificates as evidence of
      immunization may overestimate vaccination completion rates, as some certificates
      may be incorrectly completed. Education of parents, school staff and certificate
      providers should help to improve both immunization completion and documentation.

PMID- 8860387
TI  - Pattern of preschool behavior problems in New Zealand, using the Behavior Check
      List.
AB  - OBJECTIVE: The main aim of the study was to identify the pattern of behaviour
      problems in preschool children to enable early recognition and intervention.
      METHODOLOGY: Three hundred and twenty children, in eight randomly selected
      preschool centres, aged between 2.5 and 5 years, were included in the study.
      Parents completed the Behaviour Check List (BCL),a screening measure for
      preschool behaviour problems. RESULTS: Dependency, temper tantrums, and being
      difficult to manage were the commonly rated symptoms when moderate-severe
      problems were examined. Developmental problems decreased with increasing age,
      while relationship problems and worries that were cognitively mediated worsened.
      There were no major differences in the patterns between boys and girls. On cross
      cultural comparison, parents in New Zealand rated their children lower on the BCL
      compared to those in the UK. Factor analysis of the BCL yielded seven factors.
      The two main factors 'predominantly conduct' and 'predominantly emotional'
      consisted of a mixture of conduct (difficulty in managing, temper tantrums,
      sibling rivalry) and emotional (unhappy mood, worry, fears) problems. The other
      five factors were related to developmental problems. CONCLUSIONS: These results
      help clinicians identify the emerging pattern of preschool behaviour problems
      that change with increasing age and vary with differing cultures. Categorical
      presentation of preschool behaviour problems support the view that they should be
      included in a classification system.

PMID- 8860388
TI  - Assisted ventilation and survival of extremely low birthweight infants.
AB  - OBJECTIVE: To determine the incremental consumption of ventilator resources
      associated with the improving survival rate of extremely low birthweight (ELBW
      birthweight 500-999g) infants, from the time assisted ventilation was introduced.
      METHODOLOGY: Cohort study of ELBW infants born in one tertiary perinatal centre
      (The Royal Women's Hospital, Melbourne). All ELBW infants born from 1971 to 1993
      were included in the study. In hospital survival rates and patient-days of
      assisted ventilation were the main outcome measures. Discrete eras of relatively
      stable survival rate and consumption of ventilator resources were identified.
      These comprised the years 1971-74, 1977-83, 1985-90, and 1992-93. Cost
      effectiveness ratios (the incremental consumption of ventilator resources per
      additional survivor) were calculated between adjacent eras by dividing the
      increment in the consumption of ventilator resources by the increment in the
      survival rate. RESULTS: The survival rates rose progressively between eras (6.2,
      33.9, 49.1, 68.8%, respectively, as did the consumption of ventilator resources
      (0.1, 6.6, 16.2, 24.7 patient-days of assisted ventilation per livebirth,
      respectively). The cost-effectiveness ratio deteriorated initially, increasing
      from 23.2 to 63.5 additional patient-days of assisted ventilation per additional
      survivor, but then improved, falling to 43.1 additional patient-days of assisted
      ventilation per additional survivor in the last era. These changes were even more
      marked for those of birthweight 750-999g (20.0, 63.2 to 35.9 additional patient
      days of assisted ventilation per additional survivor, respectively). In contrast,
      the cost-effectiveness ratio was initially worse for those of birthweight 500-749
      g, being three-fold higher than for the larger infants, and only improved
      substantially in the last era (59.8, 58.3 to 44.1 additional patient-days of
      assisted ventilation per additional survivor, respectively). CONCLUSIONS: The
      initial deterioration in cost-effectiveness ratios between successive eras
      probably reflected the increased availability of resources for assisted
      ventilation, without any other major advances in perinatal care. The improvement
      in cost-effectiveness in the last era reflected, in part, the increased use of
      antenatal steroid therapy and the introduction of exogenous surfactant to
      neonatal intensive care.

PMID- 8860389
TI  - Nasal inflammation and chronic ear disease in Australian Aboriginal children.
AB  - OBJECTIVE: Chronic middle ear disease is common in Aboriginal children, and may
      be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of
      nasal inflammation is unknown. The study reported here was performed to define
      the role of allergy and infection in causing nasal inflammation in Aboriginal
      children with chronic middle ear disease. METHODOLOGY: Thirty-one Aboriginal
      children aged between 3 and 7 years underwent clinical assessment, audiometry and
      allergy skin tests. Nasal swabs for bacterial culture and cytology were performed
      during the winter and again in spring to identify any seasonal variation. A
      randomized trial of nasal beclomethasone for 8 weeks was conducted in children
      with abnormal tympanometry to identify the effect of therapy upon nasal cytology.
      RESULTS: Twenty-six of the 31 children had abnormal tympanograms. Average hearing
      levels were reduced in nine children. Pathogenic organisms were isolated from
      most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%),
      Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31
      children (26%) were atopic. Nasal cytology disclosed a marked neutrophil
      infiltrate (80% of cells) during the winter, which fell significantly in spring
      to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no
      effect of beclomethasone on nasal cytology. CONCLUSIONS: Chronic ear disease in
      Aboriginal children is associated with nasal inflammation, neutrophil
      infiltration and the presence of bacteria. These features suggest respiratory
      infection as the main cause of chronic nasal inflammation in Aboriginal children
      with middle ear disease. There is a seasonal variation in the severity of the
      nasal infiltrate, consistent with increased infections during winter. Despite a
      high prevalence of atopy, allergic nasal disease was uncommon.

PMID- 8860390
TI  - Gender differences in adolescent weight and shape-related beliefs and behaviour.
AB  - OBJECTIVE: To describe the beliefs, attitudes and behaviours of North Queensland
      adolescents about weight, weight loss and body shape, and to examine the
      influence of gender. METHODOLOGY: A questionnaire was used to survey 791 year 8
      adolescents from private schools in north Queensland. RESULTS: Only 41% of the
      girls and 54% of the boys were satisfied with their weight; 52% of the girls and
      27% of the boys wanted to lose weight; 52% of the girls thought their thighs were
      too fat and 26% of the boys thought their stomachs were too fat. When surveyed,
      35% of the girls and 22% of the boys were trying to lose weight. CONCLUSIONS: The
      weight loss drive, so prevalent in our culture, is already apparent among 12-14
      year old schoolchildren. The challenge is to prevent obesity without encouraging
      an accompanying obsession with weight loss; however, good information,
      appropriately delivered, may be insufficient without a change in cultural
      expectations and assistance from the fashion and advertising industries.

PMID- 8860420
TI  - A fractal approach to heterogeneous drug distribution: calcium pharmacokinetics.
AB  - PURPOSE: To point out the importance of heterogeneity in drug distribution
      processes and develop a noncompartmental approach for the description of the
      distribution of drug in the body. METHODS: A dichotomous branching network of
      vessels for the arterial tree connected to a similar venous network was used to
      describe the heterogeneity of blood flow in the successive generations of the
      networks. The relevant kinetics of drug distribution in the well perfused and the
      deep tissues was considered to take place under well stirred (homogeneous) and
      understirred (heterogeneous) conditions, respectively. RESULTS: A "homogeneous
      model" with classical kinetics (which is mathematically equivalent with the one
      compartment model) was developed for these drugs which are confined to well
      perfused ("well stirred") spaces. A "heterogeneous model" was proposed for the
      drugs reaching understirred spaces using a decreasing with time rate coefficient
      (fractal kinetics) to model the diffusion of drug under heterogeneous conditions.
      The analysis of the model equations revealed that the homogeneous model can be
      considered as a special case of the heterogeneous model. Concentration-time plots
      of multiexponential type were generated using the heterogeneous model equation.
      The empirically used power functions of time for the analysis of calcium
      clearance curves, were found to be similar to the equation adhering to the
      heterogeneous model. Fittings comparable to multiexponential models were obtained
      when the heterogeneous model equation with only one adjustable parameter was
      applied to six sets of long period calcium data. CONCLUSIONS: The heterogeneous
      processes of drug distribution in the body can obey the principles of fractal
      kinetics. Calcium clearance curves were analysed with the heterogeneous model.
      The validity of multicompartmental models which are based on the concept of
      homogeneity to describe drug distribution should be reconsidered.

PMID- 8860421
TI  - Chemotherapeutic drugs released from polymers: distribution of 1,3-bis(2
      chloroethyl)-1-nitrosourea in the rat brain.
AB  - PURPOSE: The distribution of [(3)H]BCNU following release from polymer implants
      in the rat brain was measured and evaluated by using mathematical models.
      METHODS: [(3)H]BCNU was loaded into p(CPP:SA) pellets, which were subsequently
      implanted intracerebrally in rats; [(3)H]BCNU was also directly injected into the
      brains of normal rats and rats with intracranially transplanted 9L gliomas.
      Concentrations of [(3)H]BCNU on coronal sections of the brain were measured by
      autoradiography and image processing. For comparison, the kinetics of [(3)H]BCNU
      release from the p(CPP:SA) polymer discs into phosphate-buffered saline were also
      measured. RESULTS: High concentrations of BCNU (corresponding to 1 mM) were
      measured near the polymer for the entire 30-day experiment. The penetration
      distance, defined as the distance from the polymer surface to the point where the
      concentration of [(3)H]BCNU in the tissue had dropped to 10 percent of the
      maximum value, was determined: penetration distance was 5 mm at day 1 and 1 mm at
      days 3 through 14. Local concentration profiles were compared with a mathematical
      model for estimation of the modulus phi (2), an indicator of the relative rate of
      elimination to diffusion in the brain. From day 3 to 14, phi(2) was 7, indicating
      that BCNU elimination was rapid compared to the rate of diffusive penetration
      into tissue. The enhanced penetration observed on day 1 appears to be due to
      convection of extracellular fluid caused by transient, vasogenic edema, which
      disappears by day 3. CONCLUSIONS: Polymer implants produce very high levels of
      BCNU in the brain, but BCNU penetration into brain tissue is limited due to rapid
      elimination.

PMID- 8860422
TI  - Morphological characterization of polyanhydride biodegradable implant gliadel
      during in vitro and in vivo erosion using scanning electron microscopy.
AB  - PURPOSE: The objectives of the current study are to characterize the distribution
      of the chemotherapeutic agent carmustine (BCNU) in spray dried polyanhydride
      microspheres and to describe the morphological changes that occur during the in
      vitro and in vivo erosion of the polyanhydride implant--GLIADEL, which consists
      of BCNU distributed in the copolymer matrix of poly(carboxyphenoxy
      propane:sebacic acid) in a 20:80 molar ratio (p(CPP:SA, 20:80)). METHODS:
      Scanning electron microscopy (SEM) was used to visualize the morphological
      changes of the polymer during the manufacturing process and in vitro and in vivo
      erosion. RESULTS: This study revealed that BCNU was homogeneously distributed
      within spray dried polyanhydride microspheres with no phase separation. The
      porosity of the wafer fabricated from spray dried polyanhydride microspheres
      gradually increased during erosion. During the initial period following wafer
      implantation in the brains of rats, erosion was mainly confined to the surface
      layer of the wafer with the majority of the wafer remaining intact. The eroding
      front gradually advanced from the surface to the interior of the wafer in a
      layerwise fashion, creating pores and connecting channel. Eventually both the
      interior and exterior of the wafers were eroded and the same porous structure was
      seen throughout the whole wafer. CONCLUSIONS: This study provides the first
      visual observation of the morphological changes of the GLIADEL(R) wafer during
      erosion of the polyanhydride matrix and release of the drug substance BCNU. The
      observations in this study support the conclusion that BCNU release from a
      polyanhydride wafer is controlled both by diffusion of the drug and erosion of
      the polymer matrix.

PMID- 8860423
TI  - Deformation kinetics analysis of polymeric matrices.
AB  - PURPOSE: We hypothesize that if the kinetics and the mechanisms involved in
      tablet compression are more fully understood and quantified, the parameters which
      influence tablet behavior in production may be controlled. The objective of our
      work was to obtain two deformation kinetic parameters for the predominant barrier
      to deformation, the activation volume (Vact) and the activation energy (Eact) of
      poly (methyl methacrylate-co-methacrylic acid) (PMMA/coMAA), a viscoelastic
      polymer similar to the commercial Eudragit. METHODS: Stress relaxation studies
      were performed and monitored at varying temperatures on compacts using an
      instrumented Instron testing apparatus. Solid density, microindentation hardness
      and contact area testing served to quantify the shear stress rates. RESULTS: The
      Vact was found to be 64.4 +/- 4 b(3), 63.8 +/- 11 b(3) and 79.1 +/- 8 b(3) for
      the applied strain rates of 1, 2, and 5 mm/min. The Eact for flow was determined
      to be 145 +/- 7.7, 235 +/- 8.0, and 506 +/- 2.8 x 10(1) kJ/mole(-1) for the
      applied strain rates of 1, 2, and 5 mm/min respectively. CONCLUSIONS: The average
      activation energies are indicative of strain hardening effects. The activation
      volumes and energies obtained will serve as estimates of these state variables
      for input into a particle deformation model of time-dependent compaction which is
      underway.

PMID- 8860419
TI  - Blood radicals: reactive nitrogen species, reactive oxygen species, transition
      metal ions, and the vascular system.
AB  - Free radicals, such as superoxide, hydroxyl and nitric oxide, and other "reactive
      species", such as hydrogen peroxide, hypochlorous acid and peroxynitrite, are
      formed in vivo. Some of these molecules, e.g. superoxide and nitric oxide, can be
      physiologically useful, but they can also cause damage under certain
      circumstances. Excess production of reactive oxygen or nitrogen species (ROS,
      RNS), their production in inappropriate relative amounts (especially superoxide
      and NO) or deficiencies in antioxidant defences may result in pathological stress
      to cells and tissues. This oxidative stress can have multiple effects. It can
      induce defence systems, and render tissues more resistant to subsequent insult.
      If oxidative stress is excessive or if defence and repair responses are
      inadequate, cell injury can be caused by such mechanisms as oxidative damage to
      essential proteins, lipid peroxidation, DNA strand breakage and base
      modification, and rises in the concentration of intracellular "free" Ca(2+).
      Considerable evidence supports the view that oxidative damage involving both ROS
      and RNS is an important contributor to the development of atherosclerosis.
      Peroxynitrite (derived by reaction of superoxide with nitric oxide) and
      transition metal ions (perhaps released by injury to the vessel wall) may
      contribute to lipid peroxidation in atherosclerotic lesions.

PMID- 8860424
TI  - Polyvinyl derivatives as novel interactive polymers for controlled gene delivery
      to muscle.
AB  - PURPOSE: DNA plasmids (pDNA) can be taken up by and expressed in striated muscle
      after direct intramuscular injection. We have developed interactive polymeric
      gene delivery systems that increase pDNA bioavailability to muscle cells by both
      protecting pDNA from nucleases and controlling the dispersion and retention of
      pDNA in muscle tissue. METHODS: A DNA plasmid, containing a CMV promoter and a
      galactosidase reporter gene (CMV-beta-gal), was injected either in saline or
      formulated in polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) solutions.
      Interactions between PVP and pDNA were assessed by dynamic dialysis, Isothermal
      Titration Calorimetry (ITC), and Fourier Transformed Infra Red (FT-IR)
      spectroscopy. Formulations (50 mu l) were injected into rat tibialis muscles
      after surgical exposure. Immunohistochemistry for beta-gal was used to visualize
      the sites of expression in muscle. RESULTS: Beta-gal expression using pDNA in
      saline reached a plateau while beta-gal expression using PVP formulations
      increased linearly in the dose range studied (12.5-150 mu g pDNA injected) and
      resulted in an increase in the number and distribution of cells expressing beta
      gal. The interaction between PVP and pDNA was found to be an endothermic process
      governed largely by hydrogen-bonding and results in protection of pDNA from
      extracellular nucleases. CONCLUSIONS: Significant enhancement of gene expression
      using interactive polyvinyl-based delivery systems has been observed. The
      improved tissue dispersion and cellular uptake of pDNA using polyvinyl-based
      systems after direct injection into muscle is possibly due to osmotic effects.

PMID- 8860425
TI  - Effects of polyethyleneglycol chain length and phospholipid acyl chain
      composition on the interaction of polyethyleneglycol-phospholipid conjugates with
      phospholipid: implications in liposomal drug delivery.
AB  - PURPOSE: The purpose of this study was to investigate polyethyleneglycol(PEG)
      phosphatidylethanolamine(PE) conjugate interaction with phospholipid bilayers, in
      an attempt to explain the dependence of liposome circulation time on formulation.
      METHODS: Differential scanning calorimetry, electron microscopy, dynamic light
      scattering and NMR were the major methods used in the study. RESULTS: Mixtures of
      PEG-phospholipid conjugates and phosphatidylcholine existed in three different
      physical states: a lamellar phase with components exhibiting some miscibility, a
      lamellar phase with components phase separated, and mixed micelles. Beyond 7 mol
      percent of PEG(1,000-3,000)-dipalmitoyl phosphatidylethanolamine (DPPE), and 11
      mol% PEG(5,000)-DPPE in dipalmitoyl phosphatidylcholine (DPPC), a strong tendency
      towards mixed micelle formation was observed. All concentrations of PEG(12,000)
      DPPE and PEG(5,000)-DPPE beyond 8 mol% formed phase separated lamellae with
      phosphatidylcholine. Decreasing the acyl chain length from C(16:0) to C(14:0)
      caused a decrease in tendency towards micelle formation and phase separation.
      These tendencies increased upon increasing acyl chain length to C(18:0). Phase
      separation was at least partly due to PEG chain-chain interaction. This was
      supported by an increased fraction of PEG chains exhibiting a fast NMR transverse
      relaxation in DPPC/PEG(5,000)-DPPE mixtures as compared to that in distearoyl
      phosphatidylcholine (DSPC)/PEG(5,000)-dioleoyl-PE (DOPE). CONCLUSIONS: These
      phenomena are discussed in relation to both bilayer and steric stabilization of
      liposomes, and the lack of prolonged circulation with certain formulations is
      discussed.

PMID- 8860426
TI  - Interaction of polyethyleneglycol-phospholipid conjugates with cholesterol
      phosphatidylcholine mixtures: sterically stabilized liposome formulations.
AB  - PURPOSE: The purpose of this study was to investigate polyethyleneglycol (PEG)
      phosphatidylethanolamine (PE) conjugate interaction with cholesterol-phospholipid
      mixtures in an attempt to explain the effect of cholesterol on liposome
      circulation time. METHODS: Differential scanning calorimetry, NMR, electron
      microscopy, dynamic light scattering and fluorescence spectroscopy were the major
      methods used. RESULTS: Studies performed in the absence of cholesterol indicated
      the formation of three distinct physical states depending on the chain length of
      PEG in PEG-PE. Mixed micelle formation was observed at concentrations of
      PEG(1,000)-DPPE above 7 mol-% of lipid. Phase separated lamellae were observed at
      all concentrations of PEG( 12,000)-DPPE (Bedu-Addo et al. Pharm. Res. 13:710-717
      (1996)). Upon incorporation of high concentrations of cholesterol >30 mol% into
      the lipid bilayer, the formation of phase separated lamellae was completely
      inhibited and the formation of mixed micelles significantly reduced. At high
      concentrations of PEG(1,000)-PE, solubilization of the bilayer occurred with
      preferential solubilization of cholesterol over phosphatidylcholine. Maximum
      steric stabilization (surface protection) was observed with low concentrations of
      short chain PEG-PE and high concentrations of cholesterol. CONCLUSIONS: The study
      provides a physical mechanism for the following observations: the blood
      circulation time is significantly increased or decreased with liposomes highly
      enriched with cholesterol or PEG-PE respectively.

PMID- 8860427
TI  - Fat emulsions based on structured lipids (1,3-specific triglycerides): an
      investigation of the in vivo fate.
AB  - PURPOSE: Structured lipids (1,3-specific triglycerides) are new chemical entities
      made by enzymatic transesterification of the fatty acids in the 1,3 positions of
      the triglyceride. The purpose of this study is to characterize structured lipids
      with either short chain fatty acids or medium chain fatty acids in the 1,3
      positions with regard to their hydrophobicity, and investigate the in vivo fate
      in order to evaluate the potential of structured lipids as core material in fat
      emulsions used as parenteral drug delivery system. METHODS: The lipids were
      characterized by employing reversed phase high performance liquid chromatography.
      The biodistribution of radioactively labeled emulsions was studied in rats.
      RESULTS: By employing high performance liquid chromatography a rank order of the
      hydrophobicities of the lipids could be given, with the triglycerides containing
      long chain fatty acids being the most hydrophobic and the structured lipid with
      short chain fatty acids in the 1,3 positions the least. When formulated as fat
      emulsions, the emulsion based on structured lipids with short fatty acids in the
      1,3 positions was removed slower from the general blood circulation compared to
      emulsions based on lipids with long chain fatty acids in the 1,3 positions.
      CONCLUSIONS: The type of core material influences the in vivo circulation time of
      fat emulsions.

PMID- 8860428
TI  - In vivo ESR studies on pharmacokinetics and metabolism of parenteral lipid
      emulsion in living mice.
AB  - PURPOSE: We applied non-invasive and real-time method with in vivo ESR
      spectroscopy to determining pharmacokinetics and metabolism of lipid emulsion as
      a drug carrier in living mice. METHODS: A spin-labeled triglyceride (SL-TG) was
      newly synthesized and lipid emulsion containing SL-TG was prepared. In vivo ESR
      spectra in mice were observed after intravenous administration of the lipid
      emulsion. RESULTS: In vivo ESR spectra consisted of three components, coinciding
      with the in vitro spectra of SL-TG particles, free and immobilized fatty acids.
      The amount of the components depended on both the observing domain and the period
      after administration. In the chest, all three components were observed, while SL
      TG particle was lacking in the abdomen. The half-life of the lipid particles in
      the chest was 2 hr. CONCLUSIONS: Non-invasive and real-time analysis of drug
      carriers in living animal is successfully accomplished using an in vivo ESR
      method.

PMID- 8860429
TI  - Delivery of nasal powders of beta-cyclodextrin by insufflation.
AB  - PURPOSE: Delivery of nasal powders of granulated beta-cyclodextrin by
      insufflation was studied in order to find the relationship between powder
      properties and delivery behavior. METHODS: Three nasal powder formulations,
      prepared by granulating beta-cyclodextrin with different binders, were delivered
      from a powder insufflation device, in which the dose to be emitted was loaded in
      a gelatin capsule. The delivery sequence of powder was recorded and characterized
      using an image analysis program. RESULTS: Particle size was the main parameter
      affecting nasal powder delivery, both as to the amount of dose sprayed and the
      aspect of cloud produced. Between 50-150 mu m of particle size a substantial
      change in delivery behavior of powders was observed. Powder of around 100 mu m in
      size showed useful insufflation characteristics for nasal delivery.
      Bioavailability of nasal formulations of progesterone/beta-cyclodextrin powders
      was discussed in term of delivery behavior. CONCLUSIONS: The formulation
      approaches for improving nasal delivery of powders require the use of size
      optimized carriers. Insufflation of powders over 50 mu m can favour the particle
      deposition by impaction, whereas for powders below 50 mu m, deposition by
      sedimentation is moved. beta-cyclodextrin is a suitable carrier for achieving
      high systemic availability following nasal administration of powder formulations.

PMID- 8860430
TI  - Enhancement of nasal salmon calcitonin absorption by lauroylcarnitine chloride in
      rats.
AB  - PURPOSE: We investigated optimum formulation characteristics in the nasal
      absorption of salmon calcitonin (sCT) by incorporation of acylcarnitines.
      METHODS: Nasal sCT formulations were administered to anesthetized rats. Plasma
      calcium level was measured and pharmacological bioavailability (P.bioav) was
      calculated. RESULTS: Nasal sCT absorption was significantly enhanced by
      carnitines with acyl groups of 12 or more carbon atoms. Enhancement by
      lauroylcarnitine chloride (LCC) was observed at its critical micelle
      concentration and reached a plateau at the concentration of 0.1 percent. Optimal
      absorption was achieved at a molar ratio of LCC to sCT of 5:1. Enhancement was
      not influenced by osmolarity and maximum enhancement was obtained at pHs 3.1 and
      4.0. CONCLUSIONS: The 12-carbon LCC was the strongest enhancer among
      acylcarnitines. Micelle formation played a key role in this enhancement effect.

PMID- 8860431
TI  - Pulmonary first-pass and steady-state metabolism of phenols.
AB  - PURPOSE: To study (A) the effect of the administration route (i.v. and i.t.) on
      pre- and post-absorptive metabolism of phenol and 1-naphthol by the lung and (B)
      pulmonary extraction of phenol at steady-state. METHODS: Phenols were
      administered intra-arterially, intravenously and intratracheally and the pre- and
      post-absorptive metabolism assessed by comparing the AUCs in arterial blood.
      Phenol was infused to steady-state and the pulmonary extraction assessed by
      measuring jugular vein and carotid artery blood concentrations. RESULTS: In
      contrast to previously published data (e.g., Mistry and Houston, Drug
      Metab.Dispos.l3:740-745 (1985)) we could not detect pulmonary first-pass
      metabolism of the phenols; reasons for this disparity are discussed. An apparent
      negative pulmonary extraction of phenol at steady-state was observed, probably as
      a consequence of extraction by organs which are in series, and not parallel, with
      the lungs (e.g. liver, kidneys and GIT). CONCLUSIONS: (A) Phenol and 1-naphthol
      do not undergo pulmonary first-pass metabolism. (B) Traditional methods of
      assessing organ extraction and clearance at steady-state cannot be utilised when
      metabolising organs are in series.

PMID- 8860432
TI  - Methanol inhalation: site and other factors influencing absorption, and an
      inhalation toxicokinetic model for the rat.
AB  - PURPOSE: This investigation was conducted to identify the site and
      characteristics of methanol absorption and to develop an inhalation model
      relating methanol absorption, blood concentration, and elimination. METHODS: Rats
      were exposed to methanol in chambers that allowed measurement of methanol uptake,
      ventilation, and blood concentrations; anesthetized rats with a tracheal cannula
      were examined to determine tracheal concentrations. In separate experiments,
      methanol exposed rats received an iv methanol bolus to examine the effect of
      blood methanol on ventilation and absorption; ventilation also was manipulated by
      CO(2) or pentobarbital to assess the effect of ventilation rate on methanol
      absorption. These data were combined to construct a semi-physiologic model of
      methanol uptake. RESULTS: Only 1-3 percent of inhaled methanol reached the
      trachea, primarily from systemic methanol partitioning into the trachea; blood
      methanol did not alter methanol absorption. Manipulation of ventilation and
      application of the pharmacokinetic model indicated that ventilation was less
      significant than environmental methanol concentration in determining the fraction
      of inhaled methanol absorbed, although both parameters were important
      determinants of the total mass absorbed. CONCLUSIONS: These data indicate that
      methanol uptake is a complex process that depends upon several parameters.
      Despite these complexities, a relatively simple semi-physiologic model was
      capable of describing methanol uptake over a wide range of exposure
      concentrations in the rat.

PMID- 8860433
TI  - Effects of additives on heat denaturation of rhDNase in solutions.
AB  - PURPOSE: To study the thermal stability of recombinant human deoxyribonuclease I
      (rhDNase) in aqueous solutions. METHODS: Differential scanning calorimetry (DSC)
      was used to measure the denaturation or melting temperature (T(m)) and enthalpy
      (H(m)) of rhDNase. The effects of denaturants (guanidine HCl and urea) and
      additives (mainly divalent cations and disaccharides) were investigated at pH 6
      7. RESULTS: The T(m) and H(m) of rhDNase in pure water were measured as 67.4
      degrees C and 18.0 J/g respectively, values typical of globular proteins. The
      melting peak disappeared on re-running the sample after cooling to room
      temperature, indicating that the thermal denaturation was irreversible. The
      latter was due to the occurrence of aggregation accompanying the unfolding
      process of rhDNase. Size exclusion chromatography indicated that during heat
      denaturation, rhDNase formed soluble high molecular weight aggregates with a
      molecular size >300kD estimated by the void volume. Of particular interest are
      the divalent cations: Ca(2+) stabilizes rhDNase against thermal denaturation and
      elevates T(m) and H(m) while Mg(2+), Mn(2+) and Zn(2+) destabilize it. Sugars
      also stabilize rhDNase. As expected, denaturants destabilize the protein and
      lower the T(m) and H(m). All destabilization of rhDNase can be prevented by
      adding Ca(2+) to the solutions. CONCLUSIONS: CaCl(2) and sugars were found to
      stabilize rhDNase against thermal denaturation while divalent cations, urea and
      guanidine HCl destabilize the protein. The effects could be explained by a
      mixture of mechanisms. For Ca(2+) the protective effect is believed to be due to
      an ordering of the rhDNase structure in its native state, and by prevention of
      breaking of a disulfide bridge, thus making it less susceptible to unfold under
      thermal stress.

PMID- 8860434
TI  - Isolation and characterization of a monomethioninesulfoxide variant of interferon
      alpha-2b.
AB  - PURPOSE: To isolate and characterize a monomethioninesulfoxide variant of the
      commercially available therapeutic protein interferon alpha-2b. METHODS: The
      methionine (Met)-oxidized variant was isolated by reverse-phase high performance
      liquid chromatography and characterized by SDS-PAGE, peptide mapping and mass
      spectrometric analysis of the trypsin/V8-generated peptide fragments. The
      biological and immunological activities of the isolated variant were also
      evaluated. RESULTS: The rHuIFN alpha-2b variant was found to contain a Met
      sulfoxide residue at position 111 of the rHuIFN alpha-2b molecule. The far-UV CD
      spectra showed a slight loss of alpha-helical content and an increase in the beta
      sheet contribution. The CD spectra indicate that both chromatographic conditions
      and Met oxidation contribute to the observed secondary structure changes. Both
      interferon alpha-2b main component and its methionine-oxidized variant showed
      different reactivity to monoclonal antibodies employed in immunoassays for the
      protein. CONCLUSIONS: A monomethioninesulfoxide rHuIFN alpha-2b variant was found
      to be present in the rHuIFN alpha-2b bulk drug substance in solution. The
      Met(111) residue was identified as Met sulfoxide by comparative tryptic/V8
      mapping and mass spectrometric analysis. Nevertheless, the oxidation of the
      Met(111) residue did not seem to have a detectable effect on the biological
      activity of the molecule.

PMID- 8860435
TI  - Skin penetration and sun protection factor of ultra-violet filters from two
      vehicles.
AB  - PURPOSE: In order to improve our knowledge on the efficacy and safety of
      sunscreen products, we measured the skin penetration profiles of ultra-violet
      (UV) filters in vitro and in vivo, and the corresponding sun protection factors
      (SPF) from two vehicles (an O/W emulsion-gel and petroleum jelly). METHODS: The
      UV filters tested were oxybenzone (5%, A), 2-ethylhexyl 4-methoxycinnamate
      (7.5%,B), and 2-ethylhexylsalicylate (3%,C). Two mg/cm(2) were applied for 2 min
      to 6 h. In vitro penetration measurements were performed with static diffusion
      cells. In vivo, horny layer concentrations were measured after stripping and the
      SPF evaluated as recommended by the COLIPA-guidelines. RESULTS: Significant
      differences between vehicles were noticed in vitro as well as in vivo. In vitro,
      the emulsion-gel generated higher epidermal concentrations than petroleum jelly.
      Values at 6 h, expressed as percent of the applied dose for A, B, and C were 4,
      9, and 7% for the emulsion-gel and 2, 1, and 2% for petroleum jelly. An opposite
      trend was noticed, mainly for A, in the deeper skin layers with concentrations of
      2% in the dermis and 5% in the receptor fluid for petroleum jelly and 0.6% and 1%
      for the emulsion-gel respectively. In vivo, for each UV filter, maximal stratum
      corneum levels (15 strips) were obtained at 0.5 h with percentages of the applied
      doses of 50% for the emulsion-gel and 15 percent for petroleum jelly. SPFs,
      measured 0.5 h after application amounted to 14 for the emulsion-gel and 5 for
      petroleum jelly, and decreased in both cases by a factor 2.2 after removal of non
      penetrated product. CONCLUSIONS: These preliminary results demonstrated that UV
      filters penetration and retention as well as expected SPF could be optimized by a
      suitable vehicle.

PMID- 8860436
TI  - Predicting blood-brain transport of drugs: a computational approach.
AB  - PURPOSE: This study was conducted to determine the efficacy of using nonempirical
      parameters in the estimation of blood-brain transport, inferred from central
      nervous system (CNS) activity, for a set of twenty-eight compounds. METHODS: A
      discriminant function analysis was used to construct three distinct models based
      on topological indices, a hydrogen-bonding parameter, and logP. RESULTS: These
      models correctly predict the CNS activity of twenty-seven of the twenty-eight
      compounds. CONCLUSIONS: Nonempirical parameters may be used effectively in the
      estimation the cerebrovascular penetration for known and newly designed drugs.

PMID- 8860437
TI  - Vaginal permeability and enzymatic activity studies in normal and ovariectomized
      rabbits.
AB  - PURPOSE: This study was initiated to develop an animal model, using
      ovariectomized rabbits, for the post-menopausal human, based on in vitro vaginal
      tissue permeability and aminopeptidase activity. METHODS: An enkephalin
      derivative [D-ala(2),N-methyl-phe(4)-glycol(5)][tyrosyl-3,5-(3)H] enkephalin
      {[(3)H] RX 783006), which has relative enzymatic stability to aminopeptidases and
      dipeptidyl peptidase, was used as a model peptide drug for permeability
      experiments. Aminopeptidase activity in vaginal homogenates, as well as in tissue
      pieces, was determined using 4-methoxy-2-naphthylamides of leucine, alanine,
      arginine, and glutamic acid as specific substrates. In addition, histological
      examination of normal and ovariectomized vaginal tissues was performed. RESULTS:
      Vaginal permeability of the drug was significantly increased in the
      ovariectomized compared to the intact animal. The full vaginal tissue became
      thinner and mucosal epithelial thickness was reduced about two-fold after
      ovariectomization and vaginal cells from the castrated rabbit were typically
      immature. Aminopeptidase activity, leucine aminopeptidase, aminopeptidase B and
      A, was the same in vaginal tissue homogenates and whole-tissue specimens in both
      normal and ovariectomized rabbits whereas the activity of aminopeptidase N was
      significantly decreased in ovariectomized as compared to normal rabbits.
      CONCLUSIONS: Based on the present data, the ovariectomized rabbit may be useful
      as an animal model for postmenopausal vaginal studies.

PMID- 8860438
TI  - Acute gastrointestinal toxic effects of suspensions of unencapsulated and
      encapsulated ibuprofen in rats.
AB  - PURPOSE: The study examined the gastrointestinal (GIT) toxicity effects of
      suspensions of encapsulated and unencapsulated ibuprofen in male Wistar rats.
      METHODS: Rats were randomly divided into four experimental groups and four
      control groups, and dosed with suspensions of encapsulated and unencapsulated
      ibuprofen (17 mg/kg and 44 mg/kg). Bethanechol chloride, a cholinomimetic agent
      (5 mg/kg), was administered 30 minutes after the dosing, to induce gastric
      irritation. Blood plasma concentrations were monitored in another set of rats for
      12 hours using the encapsulated and unencapsulated systems, to establish drug
      release and exposure to the mucosa. RESULTS: Evaluation of the upper GI segments
      after 7 hours revealed that the 44 mg/kg dose of the encapsulated drug
      significantly reduced the number of lesions present compared to the
      unencapsulated drug (p < 0.05). At 17 mg/kg, the encapsulated drug reduced
      toxicity, but not significantly compared to the unencapsulated ibuprofen.
      Necrosis of the mucosa was observed histopathologically in the unencapsulated
      drug at both doses, whereas the encapsulated drug treatment revealed preserved
      mucosa. The encapsulated system had a maximum plasma concentration, Cmax, and
      time taken to reach Cmax, (Tmax) of 26.7 mu g/ml +/- 1.5 and 3.6 +/- 0.2 hr,
      respectively. The area under the plasma concentration-time curve, (AUC(0-12)),
      was 158.8 +/- 23.5 mu g.h/ml, confirming drug release and absorption.
      CONCLUSIONS: Encapsulation of ibuprofen significantly reduced gastrointestinal
      toxicity especially at the higher dose level and drug was released enough to
      subject the GI mucosa to irritation, but without the usual toxic effects.

PMID- 8860439
TI  - Interspecies pharmacokinetics of a novel hematoregulatory peptide (SK&F 107647)
      in rats, dogs, and oncologic patients.
AB  - PURPOSE: To study the pharmacokinetics of SK&F 107647, a novel hematoregulatory
      agent, in rats, dogs, and patients with non-lymphoid solid tumor malignancy.
      METHODS: Sprague Dawley rats and beagle dogs (n = 6 each; 3 M, 3 F) were given 25
      mg/kg of SK&F 107467 as an iv bolus injection, and patients (n = 6; 4 M, 2 F)
      received 100 mg/kg as a 2 hour iv infusion. Plasma samples were assayed for drug
      using either HPLC (rat and dog) or RIA (human). RESULTS: In each species the
      plasma clearance (CL) of SK&F 107647 was low in relation to hepatic blood flow,
      and the volume of distribution (Vd ss) was reflective of distribution to
      extracellular body water. The plasma CL in humans was near that of average
      glomerular filtration rate. Using allometric equations for interspecies scaling
      (Y = a.W(b)), body-weight normalized human pharmacokinetic data were reasonably
      predicted using either the body weight normalized rat or the dog data. The
      allometric exponents (b) for CL, Vd(ss), and T(1/2) of SK&F 107647 were 0.63,
      0.94, and 0.29, respectively. CONCLUSIONS: Use of a limited pool of available
      animal data allowed for reasonable predictions of human pharmacokinetics of SK&F
      107647.

PMID- 8860440
TI  - Iontophoresis of nafarelin across human skin in vitro.

PMID- 8860441
TI  - Evidence for the existence of insulin-degrading enzyme on the brush-border
      membranes of rat enterocytes.

PMID- 8860442
TI  - Hot melt extrusion of acrylic films.

PMID- 8860443
TI  - Model for moisture transport into inhalation aerosols.

PMID- 8860599
TI  - Surgery for esotropia with a high accommodative convergence/accommodation ratio:
      effects on accommodative vergence and binocularity.
AB  - BACKGROUND AND OBJECTIVE: To determine the effectiveness of strabismus surgery as
      an alternative treatment for high accommodative convergence/accommodation (AC/A)
      ratio (nonrefractive accommodative) esotropia. PATIENTS AND METHODS: Twenty-three
      consecutive children with an AC/A ratio of 5:1 or greater and a distance-near
      disparity of 10 prism diopters (PD) or more were studied in a prospective design.
      Each patient was treated by recession of both medial rectus muscles for the full
      amount of esotropia measured at near fixation through the full distance hyperopic
      correction. The magnitude of eso deviation, the AC/A ratio, and the grade of
      binocularity were measured before and a minimum of 4 months after strabismus
      surgery. RESULTS: Surgery reduced the mean preoperative eso deviation at near
      fixation by a factor of 4 (from a mean of 37 PD to a mean of 9 PD). Surgery
      eliminated the need for bifocals in 96 percent of the patients. The grade of
      binocular fusion or stereopsis improved in 70 percent of the patients, remained
      unchanged in 26 percent, and was degraded in 4 percent. Three (13 percent) of the
      children became exophoric; none of the children were exotropic. CONCLUSION: These
      results demonstrate that strabismus surgery is an effective alternative to the
      long-term use of bifocals in the treatment of high AC/A ratio esotropia. Surgery
      may be more effective than bifocals in restoring normal stereopsis and binocular
      fusion.

PMID- 8860600
TI  - Optic disc topography before and after trabeculectomy in advanced glaucoma.
AB  - BACKGROUND AND OBJECTIVE: To analyze changes in the optic disc topography after
      filtration surgery. PATIENTS AND METHODS: Laser scanning tomography was performed
      in 10 eyes of 9 patients (mean age 65.6 +/- 8.1 years; age range 55 to 75 years)
      after a mean follow-up of 3.7 months, and in 8 eyes of 7 patients (mean age 63.1
      +/- 7.6 years; age range 55 to 75 years) after a mean follow-up of 13.1 months.
      RESULTS: Preoperatively, the mean intraocular pressure (IOP) was 24.4 +/- 6.9 mm
      Hg with maximal medication. Postoperatively at 3.7 months it was 11.0 +/- 2.2 mm
      Hg, and at l2.1 months it was l3.6 +/- 2.8 mm Hg. An initial reduction in IOP of
      more than 30 percent at 3.7 months was achieved without medication in all but 1
      eye. After 12.1 months, an IOP reduction of more than 30 percent was achieved in
      6 of 8 eyes (1 with medication), while 2 eyes had IOP reductions of less than 15
      percent (< or = 3 mm Hg) despite medication. In the 6 eyes, the optic disc cup
      volume showed a decrease of more than 30 percent, while the 2 eyes without marked
      IOP reductions had slight increases in cup volume. Of the 2 eyes without marked
      decreases in cup size, 1 had normal-tension glaucoma and 1 experienced an
      increase in IOP of more than 25 mm Hg during the first postoperative week.
      CONCLUSION: The postoperative IOP should be kept low enough to permit reversal of
      optic disc changes.

PMID- 8860601
TI  - Predicting long-term results of trabeculectomy from early postoperative
      intraocular pressure levels.
AB  - BACKGROUND AND OBJECTIVES: The authors retrospectively examined the potential for
      early postoperative intraocular pressure to predict the long-term results of
      initial trabeculectomies. PATIENTS AND METHODS: The records of 173 patients (207
      consecutive eyes) who underwent initial trabeculectomies, which were performed by
      one of the authors between 1983 and 1991, with a minimum follow-up of 150 days
      were reviewed. Cases of trabeculectomy combined with cataract extraction were
      excluded. RESULTS: The intraocular pressure during postoperative week 1 was the
      same for patients with successful initial trabeculectomies (success group) as it
      was for patients with unsuccessful trabeculectomies (failure group). However, the
      intraocular pressure during the second, third, and fourth weeks was significantly
      higher in the failure group (P < .001). Laser suture lysis and 5-fluorouracil had
      no influence on the fact that high intraocular pressure during the first
      postoperative week had no prognostic significance. CONCLUSION: Positive results
      on postoperative Seidel tests did not predict a poor prognosis. However, high
      intraocular pressure after the first week may require intervention because it
      predicts a poor prognosis.

PMID- 8860602
TI  - Corneal incision phacoemulsification and internal bleb revision.
AB  - BACKGROUND AND OBJECTIVE: Cataract extraction in filtered eyes often leads to
      decreased outflow and, eventually, to bleb failure. The authors describe a
      surgical technique that promotes preservation of the filtering bleb. PATIENTS AND
      METHODS: The authors retrospectively reviewed 19 eyes of 19 consecutive patients
      who underwent corneal incision phacoemulsification and simultaneous internal
      revision of the previous filtering bleb. RESULTS: The mean follow-up time was
      13.6 +/- 7.6 months. Visual acuity improved in all patients (89.4 percent
      achieved 20/40 or better). No significant difference was noted between
      preoperative and postoperative intraocular pressures and astigmatism. The bleb
      was preserved in 89.4 percent of the eyes at the time of the last follow-up.
      CONCLUSIONS: This surgical technique proved to be safe and yielded good results.

PMID- 8860603
TI  - Outcome of functioning filtering blebs after pars plana vitrectomy.
AB  - BACKGROUND AND OBJECTIVE: To determine the status of filtering bleb function
      following pars plana vitrectomy. PATIENTS AND METHODS: The authors
      retrospectively reviewed patients with functioning filtering blebs undergoing
      pars plana vitrectomy. RESULTS: Twenty-three eyes with functioning filtering
      blebs underwent pars plana vitrectomy. Postoperatively, 7/23 (30 percent) of the
      eyes had moderate (5 to 20 mm Hg) intraocular pressure (IOP), 8/23 of the eyes
      had IOP persistently greater than 20 mm Hg, and 7/23 of the eyes had IOP of less
      than 5 mm Hg. One of 7 eyes that underwent vitrectomy within 6 weeks after
      trabeculectomy maintained bleb function, whereas 6 of 16 eyes that underwent
      trabeculectomy 6 weeks or later maintained bleb function. Loss of bleb function
      occurred in the early postoperative period in the majority of the patients. Prior
      antimetabolite therapy was not associated with preservation of bleb function.
      CONCLUSION: There is a substantial risk of bleb failure following vitrectomy,
      which is in part related to the often severe nature of the diseases requiring
      vitreoretinal surgery.

PMID- 8860605
TI  - The effects of subconjunctival verapamil on filtering blebs in rabbits.
AB  - BACKGROUND AND OBJECTIVE: Verapamil is a calcium antagonist that has been shown
      to modulate wound healing through multiple mechanisms. The wound modulating
      effects of verapamil were studied in a rabbit model of filtering surgery.
      MATERIALS AND METHODS: Twenty New Zealand albino rabbits underwent a fistulizing
      procedure, with either verapamil or saline injected subconjunctivally daily for 6
      days following surgery. The animals were sacrificed at 20 days after the
      fistulizing procedure. The effectiveness of verapamil in modulating wound healing
      was evaluated by bleb patency testing, histology, measurement of scar thickness,
      and counts of bromodeoxyuridine (BrdU)-labeled cells at the sclerostomy site.
      RESULTS: The group treated with verapamil had a 44 percent patency rate compared
      with 10 percent in the control group (P < .05), a mean scar thickness of 195.96
      +/- 68 mu m compared with 313.55 +/- 110.4 mu m in the control group (P < .02),
      and a mean BrdU-labeled cell count of 15.5 +/- 14.7 compared with 26.3 +/- 17.0
      in the control group (P < .002). CONCLUSION: Verapamil was effective in reducing
      scar formation at the sclerostomy site. At the doses administered, verapamil
      appeared to modulate wound healing in filtering blebs in the rabbit model.
      Further studies are needed to determine the dose-response and the efficacy of the
      drug in nonhuman primates.

PMID- 8860604
TI  - Ocular toxicity following topical application of anesthetic cream to the eyelid
      skin.
AB  - BACKGROUND AND OBJECTIVE: The use of topical anesthetic cream in the periorbital
      region may be of clinical value. The potential for toxic effects from such use
      has not been studied in a controlled manner. This study was performed to evaluate
      the potential ocular toxicity of anesthetic cream topically applied to the eyelid
      in an animal model. MATERIALS AND METHODS: Ten rabbits underwent periorbital
      eutectic mixture of local anesthetics (EMLA) (2.5 percent lidocaine and 2.5
      percent prilocaine) application and were observed for evidence of gross or
      microscopic ocular toxicity. Baseline external and anterior segment examinations
      were performed, including biomicroscopy and fluorescein staining, after which a
      standard quantity of EMLA cream (0.75 g) was applied along the upper eyelid and
      covered with an occlusive dressing. After 1 hour of treatment, the eyelid and
      anterior segment were examined for evidence of adverse reaction. The eyelids were
      excised and examined histopathologically. RESULTS: No significant adverse effects
      were noted on external lid and anterior segment examination. The histopathologic
      findings were within normal limits. CONCLUSIONS: This study suggests that
      external application of EMLA cream to the eyelid does not induce local toxicity
      in the rabbit model. The external application of EMLA cream may be safe in the
      periorbital region.

PMID- 8860647
TI  - The secretion of active recombinant human gastric lipase by Saccharomyces
      cerevisiae.
AB  - The expression of the complete human gastric lipase (HGL) gene in Saceharomyces
      cerevisiae grown in defined medium resulted in the secretion of active
      recombinant HGL (rec.HGL) to levels of up to approximately 11 mg/liter. Of the
      total measurable HGL activity, 90% was detected by assaying intact cells,
      suggesting that the majority of rec.HGL produced was secreted but stayed attached
      to the cell wall. The remaining 10% was present in the growth medium and from
      this source active rec.HGL was purified 300-fold by a combination of hydrophobic
      interaction and ion-exchange chromatography. Rec.HGL migrated on reduced SDS-PAGE
      as three bands with estimated molecular masses of 47,45, and 43 kDa. All three
      forms cross-reacted with an antibody raised to natural HGL and their treatment
      with Endo H showed them to be N-linked glycosylation variants of a single
      polypeptide. The 47-kDa species was isolated using lentil lectin Sepharose 4B and
      shown to possess a specific activity comparable to that of the natural enzyme.
      Rec.HGL had an acid pH activity optimum using either tributyrin or olive oil as
      substrate and did not lose activity if incubated in the presence of pepsin at pH
      2.0. These results demonstrate that HGL secreted by Saccharomyces cerevisiae
      retained those properties of the natural enzyme required for its use in the
      treatment of pancreatic insufficiency.

PMID- 8860648
TI  - Expression, isolation, and characterization of a signal sequence-appended
      chimeric precursor protein.
AB  - This report describes the properties and the functional utility of an unprocessed
      precursor protein overproduced in Escherichia coli. The precursor protein is from
      a fusion between DNA sequences coding for the alkaline phosphatase signal
      sequence and the full-length of rat liver cytochrome b(5). The intact precursor
      protein accumulated in the membranes represented to over 5% of the total
      bacterial protein. A procedure involving disruption of the bacterial cells by
      sonication, isolation of the membranes by differential centrifugation,
      solubilization with a polar solvent, and ion-exchange chromatography provided
      milligram quantities of the undegraded precursor in a homogeneous and soluble
      form. The chimeric precursor protein displayed a characteristic b-type
      hemoprotein spectrum, identical to that of the native cytochrome b(5). The
      properties of the precursor protein have been examined by a range of biophysical
      and biochemical methods. Molecular modeling suggests an amphipathic structure in
      which a fully preserved soluble core of cytochrome b(5) is terminally bonded by
      hydrophobic interactions between the amino-terminal signal sequence and the
      carboxy-terminal membrane anchoring hemoprotein sequence. The precursor substrate
      was recognized and efficiently cleaved by signal peptidase.

PMID- 8860606
TI  - In vitro evaluation of polymeric matrix and porous biodegradable reservoir
      devices for slow-release drug delivery.
AB  - BACKGROUND AND OBJECTIVE: Biodegradable polymeric devices were evaluated in vitro
      for intravitreal drug delivery. MATERIALS AND METHODS: The matrix (short-term
      drug delivery) and the porous (longer-term drug delivery) reservoir devices were
      made from polycaprolactone of two molecular weights (30,000 and 56,000). Matrix
      devices were loaded with 5-fluorouracil or ganciclovir. Porous reservoirs were
      loaded with 5-fluorouracil, ganciclovir, 5-carboxyfluorescein, or foscarnet. The
      release was monitored in phosphate-buffered solution using ultraviolet
      spectrophotometry. RESULTS: Release from the matrix devices was characterized by
      an initial burst, followed by a nonlinear release. The porous reservoirs
      demonstrated zero order linear release of drugs, sustained up to 250 days in this
      experiment. CONCLUSIONS: The matrix device is capable of sustained release over
      several months; the porous reservoir can deliver drugs for over 1 year. Further
      studies are needed to evaluate in vivo biodegradation behavior and toxicity of
      drugs used for sustained release.

PMID- 8860649
TI  - Bovine beta-casein expressed in transgenic mouse milk is phosphorylated and
      incorporated into micelles.
AB  - Transgenic mice carrying the bovine beta-casein gene linked to the promoter
      sequence of the sheep beta-lactoglobulin milk protein gene were produced. Four of
      seven lines expressed the transgene protein with mice from the two highest
      expressing lines producing 4 to 5 mg ml(-1) of this protein in their milk. The
      foreign protein was associated with the casein micelles and did not segregate
      into the whey fraction on centrifugation of milk samples. Following purification,
      the protein was characterized by amino acid analysis, gel electrophoresis,
      capillary zone electrophoresis, and trypsinolysis. The results showed that the
      transgene protein was authentic, phosphorylated bovine beta-casein A(1).

PMID- 8860650
TI  - Production of human pancreatic ribonuclease in Saccharomyces cerevisiae and
      Escherichia coli.
AB  - Human pancreatic ribonuclease (HP-RNase) has considerable promise as a
      therapeutic agent. Structure-function analyses of HP-RNase have been impeded by
      the difficulty of obtaining the enzyme from its host. Here, a gene encoding HP
      RNase was designed, synthesized, and inserted into two expression vectors that
      then direct the production of HP-RNase in Saccharomyces cerevisiae (fused to
      either an unmodified or a modified a-factor pre-pro segment) or Escherichia coli
      (fused to the pelB signal sequence). HP-RNase produced in S. cerevisiae was
      secreted into the medium as an active enzyme, isolable at 0.1-0.2 mg/liter of
      culture. This isolate was heterogeneous due to extensive glycosylation and
      incomplete maturation of the pre-pro segment. HP-RNase produced in E. coli with
      the pET expression system was purified from the insoluble fraction of the cell
      lysate. Renaturation of the reduced and denatured protein produced active,
      homogeneous enzyme recoverable at 1 mg/liter of culture. The N terminus of the HP
      RNase produced from the bacterial expression system was processed fully in vivo.
      The yeast system, combined with techniques that allow detection of picograms of
      ribonuclease activity, offers a sensitive probe for studies of post-translational
      modification and secretory targeting in eukaryotic cells. The bacterial system
      enables studies both to reveal new structure-function relationships in
      ribonucleases and to evaluate the use of HP-RNase as a cytotoxin that is
      tolerated by the human immune system.

PMID- 8860651
TI  - Expression of human growth hormone in silkworm larvae through recombinant Bombyx
      mori nuclear polyhedrosis virus.
AB  - We have generated a recombinant Bombyx mori nuclear polyhedrosis virus, vBmhGH,
      harboring the full length human growth hormone gene (2.4-kb genomic DNA, with
      four introns and the signal peptide sequences) under the control of the
      polyhedrin promoter. BmN cells in culture infected with the recombinant virus
      showed the presence of RNA corresponding to the authentic growth hormone mRNA as
      well as its incompletely processed precusor. Electrophoretic analysis and
      immunoprecipitation of proteins of recombinant virus-infected BmN cells revealed
      the presence of the growth hormone protein. Infection of silkworm larvae with
      vBmhGH led to the synthesis and efficient secretion of the protein into
      hemolymph. The recombinant human growth hormone was biologically active in a
      radioreceptor competition binding assay. The secreted protein was isolated and
      purified to homogeneity by a single step immunoaffinity chromatography, to a
      specific activity of 2.4 x 10(4) U/mg. The recombinant hGH retained the
      immunological and biological properties of the native peptide. We conclude that
      BmNPV vectors can be used successfully for expressing chromosomal genes harboring
      multiple introns.

PMID- 8860652
TI  - Vector-derived expression of recombinant rat interleukin-6.
AB  - Rat interleukin-6 (IL-6) cDNA, coding for an important inflammation- and immune
      regulatory polypeptide cytokine, was cloned into the novel expression vector
      pH6EX3 which directs the synthesis of inserted genes as a fusion protein with
      histidine hexapeptide (HH). The resultant vector (pRIL6.992) was shown to produce
      significant amounts of recombinant rat IL-6 fusion protein with HH at its N
      terminus in various strains of Escherichia coli. The expression of the HH-IL-6
      fusion protein was demonstrated to be under the control of the tac promoter and
      could be induced by IPTG. This protein was isolated from bacterial inclusion
      bodies and purified to homogeneity in a one-step procedure by affinity
      chromatography using a nickel-chelating column. The HH-IL-6 fusion protein
      isolated in this manner was biologically active as determined by hepatocyte
      stimulation and B9 hybridoma growth assays. Further, this activity was
      neutralized with a polyclonal antiserum raised against rat IL-6 protein generated
      in a novel fashion from rabbits infected with a recombinant human type-5
      adenovirus vector expressing rat IL-6 protein (Ad5E3rIL6). The recombinant HH-IL
      6 protein was then used to boost Ad5E3rIL6-immunized rabbits. This resulting
      antiserum was shown to neutralize recombinant and natural rat and murine IL-6
      bioactivity in vitro and was useful in Western blot analysis and
      immunohistochemistry of rat IL-6.

PMID- 8860653
TI  - Rescue of immunoglobulins from insolubility is facilitated by PDI in the
      baculovirus expression system.
AB  - A substantial fraction of immunoglobulin heavy and light chain polypeptides were
      insoluble when expressed in the baculovirus-insect cell expression system. In the
      presence of coexpressed heterologous protein disulfide isomerase (PDI), however,
      the solubility of the immunoglobulins was enhanced and IgG was secreted at higher
      levels from baculovirus-infected Trichoplusia ni insect cells. Pulse-chase
      experiments indicated that some immunoglobulin polypeptides were initially
      insoluble in the presence of PDI but subsequently were rescued in a soluble form
      competent for IgG assembly and secretion. Recovery of the insoluble
      immunoglobulins was not observed in the absence of coexpressed PDI. Even after
      treatment of insect cells with tunicamycin to inhibit N-glycosylation of
      immunoglobulin heavy chains, coexpressed PDI was able to salvage insoluble
      immunoglobulins and secrete these modified glycoforms. The capacity for PDI to
      rescue immunoglobulins was also demonstrated in vitro where immunoglobulin heavy
      chains and light chain dimers were salvaged from aggregates of denatured IgG. PDI
      mediated rescue of proteins, perhaps assisted by chaperones and other foldases,
      may be important in vivo where insolubility is a common occurrence for newly
      synthesized polypeptides.

PMID- 8860654
TI  - Specific replacement of consecutive AGG codons results in high-level expression
      of human cardiac troponin T in Escherichia coli.
AB  - The adult isoform of human cardiac troponin T (TnT) contains 288 amino acids, 14
      of which (4.9%) are encoded by the rarely used arginine codons (12 AGG, 2 AGA) in
      Escherichia coli genes. To generate sufficient quantity of TnT protein for
      antibody production, we cloned the corresponding cDNA and expressed it in E.
      coli. A low-level expression of TnT that comprised only about 1% of total cell
      protein was initially observed with the use of the native cDNA. The existence of
      two pairs of consecutive AGG codons AGG(165) AGG(166) and AGG(215) AGG(216) in
      the cDNA was suspected to be the main cause for this low-level expression. These
      two pairs of consecutive AGG codons were successively replaced with the major
      synonymous codon CGT by site-directed mutagenesis. As suspected, a 10-fold
      increase in TnT expression was obtained when one pair of the rare arginine codons
      was replaced and a 40-fold increase was achieved when both pairs of the rare
      codons were replaced. Our finding demonstrates the importance of consecutive rare
      codons in the suppression of high-level expression of heterologous proteins in E.
      coli and suggests that in order to maximize protein expression, a similar
      approach may be taken with other genes which contain consecutive rare codons.

PMID- 8860655
TI  - Sequential precipitation with reversibly soluble insoluble polymers as a
      bioseparation strategy: purification of beta-glucosidase from Trichoderma
      longibrachiatum.
AB  - Precipitation of proteins/enzymes with reversibly soluble-insoluble polymers is a
      simple approach which can be easily scaled up. It is shown here that considerable
      purification may be achieved if more than one polymer (chosen judiciously) is
      used in sequence for purification. The principle is illustrated with purification
      of beta-glucosidase from a commercial preparation of Trichoderma longibrachiatum.
      Precipitation with chitosan removed cellulase activity from the preparation with
      4-fold purification and 99% recovery of beta-glucosidase activity in the
      supernatant. The treatment of the supernatant with Eudragit S-100 precipitated
      98% of the enzyme activity. The two different elution procedures gave 82%
      recovery (with 14-fold purification) and 86% recovery (with 12-fold purification)
      of the enzyme activity from the precipitate. A low molecular weight protein still
      present in these preparations could be removed by gel filtration. This finally
      yielded an electrophoretically homogeneous enzyme with 74% recovery and 29-fold
      purification.

PMID- 8860656
TI  - Functional and structural properties of the homogeneous beta-glycosidase from the
      extreme thermoacidophilic archaeon sulfolobus solfataricus expressed in
      Saccharomyces cerevisiae.
AB  - A protein with beta-glycosidase activity from Sulfolobus solfataricus (S beta
      gly) was expressed in the yeast Saccharomyces cerevisiae. The purification
      procedure was made fast and easy by employing a single chromatographic step.
      After 5.8-fold purification, the cell extract gave a homogeneous enzyme at 166
      U/mg. The recombinant enzyme was functionally and structurally similar to the
      wild-type enzyme. Kinetic experiments showed the same wide substrate specificity;
      in fact, the expressed enzyme hydrolyzed beta-D-gluco-, fuco-, and galactosides
      and a large number of glucoside dimers and oligomers, linked beta 1 -> 4.
      Moreover, the molecular mass of the enzyme was estimated to be 60 kDa by SDS-PAGE
      and 240 kDa by gel filtration, glycerol gradient, and ultracentrifugation
      analyses, indicating that the enzyme has a tetrameric structure. The N-terminal
      amino acid sequence, the temperature dependent activity, and content of secondary
      structure were similar to those of the wild-type enzyme. CD spectral and kinetic
      analyses showed that the only differences from the wild-type enzyme consist of
      the absence of lysine methylation, the presence of some glycosylated amino acid
      residues, and lower thermostability. Furthermore, calorimetric analyses on the
      expressed protein indicated values of delta dH = 5072 kJ/ mol and delta (d)C(p)=
      100 kJ/mol, appreciably lower than those of the wild-type protein.

PMID- 8860657
TI  - A rapid purification method for soybean Bowman-Birk protease inhibitor using
      hydrophobic-interaction chromatography.
AB  - A protein fraction was isolated from defatted soybean flour by extraction at acid
      pH, 40% ammonium sulfate precipitation, hydrophobic interaction chromatography,
      and gel filtration chromatography. SDS-PAGE, under reducing conditions, confirmed
      it as a homogeneous preparation. This conclusion was consistent with N-terminal
      amino acid sequence data (20 cycles) which showed a major sequence identical to
      those reported for soybean Bowman-Birk-type protease inhibitor (BBI), and also
      indicated a minimum 95% purity based on recoveries of PTH-amino acid residues.
      The purified fraction inhibited both trypsin and chymotrypsin with average
      specific activities of 350 and 672 units mg(-1), respectively. Compared with
      classical BBI purification, this procedure is very rapid requiring only 72-96 h
      to achieve a yield of 37 mg purified BBI per 200 g starting material.

PMID- 8860658
TI  - Characterization and partial purification of human monoamine oxidase-B expressed
      in Escherichia coli.
AB  - Monoamine oxidases (MAO-A and MAO-B) are enzymes that play a key role in the
      degradation of endogenous and dietary monoamines. A full-length cDNA of the B
      type of MAO, isolated from a human liver cDNA library, was cloned into a
      prokaryotic expression vector (pET11c). Escherichia coli which was transfected
      with the recombinant plasmid expressed an insoluble protein product with the
      expected molecular weight (65 kDa). However, in the inclusion body fraction,
      where most of the recombinant protein was present, no MAO activity was observed.
      In contrast, the membrane fraction of the bacterial lysates expressed catalytic
      activity as estimated by oxidative deamination of beta-phenylethylamine and
      tyramine. The active enzyme protein was solubilized with Triton X-100 and partly
      purified (80-fold) on a DEAE-Sepharose column. This enzyme activity showed
      properties very similar to those of human brain and platelet MAO-B. Moreover, a
      single band of the expected molecular size was observed on an immunoblot. The
      peak fraction from the DEAE-Sepharose separation was further purified on a
      tyramine-Sepharose column, yielding a highly purified enzyme (190-fold), visible
      as a band on a sodium dodecyl sulfate-containing polyacrylamide gel.

PMID- 8860659
TI  - Site-directed mutagenesis techniques in the study of Escherichia coli serine
      hydroxymethyltransferase.
AB  - The 3340-bp fragment containing the Escherichia coli glyA gene coding for serine
      hydroxymethyltransferase was reduced in size by PCR, and the 1600-bp fragment
      obtained was cloned into the vector pBR322 in both orientations (5'-3', and 3'
      5'). This DNA manipulation allowed us to perform site-directed mutagenesis by PCR
      on the glyA gene. To overcome the problem of the presence of wild-type protein in
      the various mutant enzyme preparations, the E. coli strain GS245 used to express
      recombinant serine hydroxymethyltransferase was made recA deficient through
      generalized transduction mediated by phage P1. The new strain was used for the
      production of a mutant form of the enzyme, in which the pyridoxal 5'-phosphate
      binding lysine was substituted by a glutamine. The preparation of this mutant
      form was completely devoid of wild-type enzyme contamination and measurements of
      its catalytic activity in the transamination reactions of L- and D-alanine
      confirmed the suggestion that the active site lysine is not the base that removes
      the alpha-proton from the substrate.

PMID- 8860660
TI  - Hepatocyte growth factor (HGF) is a copper-binding protein: a facile probe for
      purification of HGF by immobilized Cu(II)-affinity chromatography.
AB  - Hepatocyte growth factor (HGF) is a multifunctional protein expressed in a
      variety of cell types and tissues. Here we describe a novel one-step method to
      separate and identify HGF, based on a unique interaction between HGF and Cu(II).
      Conditioned medium (CM) from mouse 3T3-L1 adipocytes which contains HGF or
      purified human recombinant HGF was used for analysis. Mouse 3T3-L1 adipocyte CM
      was applied to a Cu(II)-affinity column and rinsed with equilibration buffer. HGF
      was then eluted with 10 mM imidazole. Fractions eluted from the column were
      analyzed by SDS-PAGE. Analysis by silver staining revealed an 85kDa protein.
      Further analysis by Western blotting with polyclonal anti-HGF IgG demonstrated
      that this protein corresponded to HGF. Human recombinant HGF, when applied to a
      Cu(II)-affinity column, showed a stronger affinity to Cu(II) than did mouse HGF.
      Human recombinant HGF was not eluted from the Cu(II) column with either 10 or 20
      mM imidazole; however, it was readily eluted with 40 mM imidazole. The
      percentages of recovery of both human and mouse HGF were greater than 90%. Both
      mouse HGF and human recombinant HGF eluted from the Cu(II)-affinity column
      retained their biological activity as measured by HGF-induced cell proliferation
      of Mv1Lu cells. Our findings provide the first evidence that HGF is a copper
      binding protein and that a Cu(II)-affinity column can be used for efficient one
      step purification of biologically active HGF.

PMID- 8860661
TI  - Effects of a hepato-protective agent and a hepato-secreting chelator on cadmium
      induced nephrotoxicity in Syrian hamsters.
AB  - Cadmium (Cd)-induced nephropathy in male Syrian hamsters was treated with D/L
      penicillamine (D/L-p) or neomynophagen C (NMC). The subcutaneous injection of
      CdCl(2), 3 mg/kg, three times a week led to marked renal damage, ie., increased
      proteinuria and the excretion of urinary N-acetyl-beta-D-glucosaminidase (NAG) as
      compared with the saline-injected controls. Cd-treated hamsters that were
      injected intraperitoneally with D/L-p, 0.1 mg/kg, five times a week, showed less
      renal damage, including a reduction in urinary protein from 3.60 + or - 0.42 to
      1.77 + or - 0.7 mg/d. NMC-treated hamsters showed a reduced excretion of NAG
      (from 1.47 +/ - 0.34 to 0.91 + or - 0.68 u/d). The concentration of Cd in renal
      cortical tissue was reduced slightly (from 2.78 + or - 0.08 to 2.34 + or - 0.3
      mg/g.prot) by NMC treatment, but not by D/L-p. The elevated malondialdehyde (MDA)
      in renal cortical tissue was unaffected by administering D/L-p or NMC. The
      concentration of glutathione (CSH) in the renal cortex was not elevated after
      administering Cd, but the ratio of the reduced to the oxidized GSH was elevated.
      The Cd induced liver dysfunction, as compared with untreated controls. The
      dysfunction was improved slightly by NMC administration, but not by that of D/L
      p. Changes in renal morphology induced by Cd involving marked degeneration and
      necrosis of tubules as shown by light microscopy, were unaffected by treatment
      with D/L-p or NMC. We thus demonstrated the efficacy of D/L-p of NMC in treating
      the nephropathy induced by Cd in hamsters. The mechanism of therapeutic effect is
      not known.

PMID- 8860662
TI  - Occurrence of heavy metals, sodium, calcium, and potassium in human hair, teeth,
      and nails.
AB  - Heavy metals in biological samples: nails, teeth, and hair were examined during
      1991-1993. Investigations of biological samples (hair n = 249 samples, teeth n =
      145, nails n = 80 samples) were provided for inhabitants of selected towns in
      Beskid Slaski. The towns are small mountain towns in southern Poland: Wista,
      Szczyrk, Istebna, Koniakow, and Jaworzynka. The analysis of ANOVA and MANOVA
      variances were used for biological samples in the context of age, sex, and type
      of samples for 12 elements (Pb, Cd, Cr, Zn, Fe, Cu, Mn, Ni, Co, Ca, Na, and K).
      The matrix correlation and cluster analysis were applied to explain the behavior
      of metals in human hair, teeth, and nails.

PMID- 8860663
TI  - Dietary folate affects the response of rats to nickel deprivation.
AB  - Because vitamin B12 and Ni are known to interact and because of the similar
      metabolic roles of vitamin B12 and folate, an experiment was performed to
      determine the effect of dietary folate on Ni deprivation in rats. A 2 x 2
      factorially arranged experiment used groups of nine weanling Sprague-Dawley rats.
      Dietary variables were Ni, as NiCl(2) 6H(2)0, 0 or 1 mu g/g; and folic acid, 0 or
      2 mg/kg. The basal diet, based on skim milk, contained less than 20 ng Ni/g.
      After 54 d, an interaction between dietary Ni and folate affected several
      variables including erythrocyte folate, plasma amino acids, and femur trace
      elements. For example, folate deprivation decreased erythrocyte folate; folate
      supplementation to the Ni-supplemented rats caused a larger increase in
      erythrocyte folate concentration than did folate supplementation to the Ni
      deprived rats. Also, dietary Ni affected several plasma amino acids important in
      one-carbon metabolism (e.g., Ni deprivation increased the plasma concentrations
      of glycine and serine). This study shows that dietary Ni, folate, and their
      interaction can affect variables associated with one-carbon metabolism. This
      study does not show a specific site of action of Ni but it indicates that Ni may
      be important in processes related to the vitamin B12-dependent pathway in
      methionine metabolism, possibly one-carbon metabolism.

PMID- 8860681
TI  - Development of superparamagnetic nanoparticles for MRI: effect of particle size,
      charge and surface nature on biodistribution.
AB  - Twelve superparamagnetic Magnetite-Dextran (MD) nanoparticles potentially useful
      as contrast agents for Magnetic Resonance Imaging (MRI), with different sizes,
      charges and surface natures, were produced and internally labelled with (59)Fe in
      order to investigate the effect of their physicochemical properties on their
      biodistribution in mice. In a first step, neutral MD particles of a size 33-90.6
      nm were studied. Next, the influence of charge was investigated with negative and
      positive particles (MDL, MDD, MDDEAE). The former (-25, -30 mV) were small,
      around 30 nm in size whereas the latter (+20 mV) were larger (104 nm). The effect
      of surface nature was evaluated using MD particles coated with polyoxyethylene
      polyoxypropylene copolymers (Synperonic: these MDP particles were neutral and
      larger in size (65.9-76.4 nm). Experiments showed that 20 min post-injection (2
      mg Fe/kg), liver uptake was enhanced when the mean diameter increased: 22% for
      the smallest and 42% for the largest. It was up to 3 X lower for electrically
      neutral particles than for charged particles. Coated particles presented higher
      vascular persistence. The diagnostic potential for liver, lymph node or vascular
      imaging were discussed.

PMID- 8860682
TI  - Preparation of biodegradable microcapsules containing zidovudine (AZT) using
      solvent evaporation technique.
AB  - Sustained release biodegradable microcapsules of AZT were prepared using
      different concentrations of copolymer of poly(lactic/glycolic) acid (PLGA 50:50
      and PLGA 90:10). Solid microcapsules were collected following the complete
      evaporation of the solvent. The yield of microcapsules was increased two fold
      with a two-fold increase of the polymer concentration. The efficiency of
      encapsulation of AZT was also increased with the increase of the polymer
      concentration. These microcapsules were characterized using scanning electron
      microscopy. The dissolution of AZT from the microcapsules of PLGA (50: 50) was
      higher than the microcapsules of PLGA (90:10); the PLGA (50:50) microcapsules
      containing 1:10 drug/polymer ratio showed higher dissolution than the
      microcapsules containing 1:20 drug/polymer ratio. The PLGA (90:10) microcapsules
      containing 1:6 drug/polymer ratio showed higher dissolution than the
      microcapsules containing 1:10 drug/polymer ratio. In conclusion, the dissolution
      of AZT was dependent on the type of the copolymer used and the relative
      concentrations of the drug and the copolymer.

PMID- 8860683
TI  - Liposomal formulations containing sodium mercaptoundecahydrododecaborate (BSH)
      for boron neutron capture therapy.
AB  - Sodium mercaptoundecahydrododecaborate or BSH is a compound most widely used for
      boron neutron capture therapy (BNCT). Liposome formulations containing BSH, with
      or without steric stabilization, were prepared as potential agents for delivery
      of boron compounds for BNCT. Liposomes composed of DPPC/CHOL in a molar ratio 1:1
      (PEG concentration: 5 mol%) were prepared having an average diameter in the range
      of 100-110 nm 200 mu L of liposomes (l.88 mg phospholipid/mouse and 3.5-5.8 mg
      BSH/kg body weight) were injected in mice via the tail vein. Both types of
      liposomes resulted in a significant improvement in the circulation time of BSH
      compared to that obtained previously after injecting free BSH. The mean percent
      injected BSH remaining in circulation at the end of 24 h was 19% for the PEG
      liposomes compared to the corresponding value of 7% for the conventional
      liposomes. The mean percent uptake by the liver and spleen was not significantly
      different for the two types of liposomes; the blood/RES ratios were higher for
      the PEG-liposomes at all time points indicating that a higher fraction of
      injected BSH was available in circulation. The PEG-liposomes could be further
      explored as a means of enhance boron drug delivery to tumor cells for BNCT.

PMID- 8860685
TI  - In-vivo studies on dexamethasone sodium phosphate liposomes.
AB  - Dexamethasone Sodium Phosphate (DSP) is a water soluble anti-inflammatory steroid
      commonly used in the therapy of serious types of ophthalmic inflammation. It has
      been demonstrated that unless the corneal epithelium is damaged, DSP is poorly
      absorbed by the cornea (Kupferman et al. 1974). Thus, it is doubtful whether such
      a drug would cure inflammation of the anterior segments. For this purpose,
      several liposomal DSP formulations containing phospholipid: charge inducer:
      cholesterol in molar ratios of 10:1:4 were investigated. Both gel state (PL 90H:
      SA: Cho1) and liquid state (PL 100: SA: Cho1) liposomes were prepared. For the
      preparation of liposomes, the film method followed by bath sonication was used.
      Liposomes were labelled with (99m)-Tc and administered intra-ocularly to New
      Zealand white rabbits weighing 2.5-3 kg for in vivo experiments. The
      biodistribution of the labelled liposomes were determined. For this purpose, eye
      segments (such as cornea, lens, iris, ciliar body, vitreous, aqueous humor,
      conjuctiva and sclera) and RES organs (such as liver, pancreas, spleen) were
      removed at fixed time intervals. In the present study, the efficiency of
      liposomes for the delivery of water-soluble drugs was evaluated in rabbit eyes
      using DSP as a model drug in different liposomal formulations.

PMID- 8860684
TI  - Preparation and characterization of multiple emulsion based systems for
      controlled diclofenac sodium release.
AB  - Multiple w/o/w type emulsions were prepared and stabilized through interfacial
      complex films formation as a result of interaction of macromolecules like
      gelatin, bovine serum albumin (BSA), polyvinyl alcohol (PVA) and polyacrylic acid
      (PAA) (each present in internal aqueous phase separately) with sorbitan
      monostearate (Span 60) present in the middle oil phase. The stability of prepared
      emulsions was assessed using microscopic analysis which showed no significant
      changes in the average size of globule and number of droplets counted per cubic
      mm on storage. Viscosity and zeta potential studies revealed appreciable
      stability of the multiple emulsions. The multiple emulsion containing
      macromolecules in their internal phase demonstrated better entrapment efficiency.
      Intramuscular injection of drug in a w/o/w emulsion formulation provided a
      protracted drug plasma profile for diclofenac sodium.

PMID- 8860686
TI  - Solvent and plasticizer influences on ethylcellulose-microcapsules.
AB  - Variations in microencapsulation processes give rise to different products and it
      seems there are no firm rules. It is thus difficult to know what kind of product
      will be obtained before the research is carried out. Changes in temperature,
      rate, time and type of stirring can cause great modifications in the system, most
      of which are responsible for variations in standard techniques. In our study, we
      investigate the solvent influence on ethylcellulose (EC) microcapsule formation.
      We have selected four different solvents: ethanol as an aqueous solvent and
      acetone, chloroform and toluene as organic solvents. Diclofenac sodium (DFNa), a
      non-steroidal anti-inflammatory agent, has been used as an encapsulated substance
      as it is inactivated in the gastric juices. This polymer and microencapsulation
      process was selected after an exhaustive study with different polymers and
      processes. Once the solvent influence was determined, ethylphthalate was
      incorporated in one type of microcapsule in order to study the influence of this
      plasticizer on drug release by the modification of film-permeability.

PMID- 8860687
TI  - Chitosan/calcium alginate microcapsules for intestinal delivery of
      nitrofurantoin.
AB  - A new sustained-release dosage form of nitrofurantoin (NF) as microcapsules has
      been prepared by a mild chitosan/calcium alginate microencapsulation process.
      These microcapsules have been prepared by adding, dropwise, a solution of sodium
      alginate containing NF into a chitosan-CaCl(2) system. About 70-80% of the drug
      is released into phosphate buffer, pH = 7.4 within 6 h. Drug release into the
      gastric medium is found to be relatively slow compared to that into the
      intestinal medium. From scanning electron microscopic studies, it appears that
      the chitosan modifies the NF-alginate microspheres. These findings suggest the
      possibility of modifying the formulation to obtain the controlled release of NF
      in an oral sustained-delivery system.

PMID- 8860688
TI  - Preparation and characterization of a complex microencapsulated diet for striped
      bass Morone saxatilis larvae.
AB  - The nutritional requirements of marine fish larvae are not well understood,
      primarily due to the lack of biochemically defined diets acceptable by the
      larvae. This study describes the methodology for the preparation and the
      characterization of a complex protein-walled microcapsule (CPWC) containing lipid
      walled capsules (LWC). The CPWC were prepared by atomizing a mixture of casein,
      LWC and other dietary materials into a cyclohexane solution containing 1% (v/v)
      cross-linking reagent, adipoyl chloride. The primary purpose of complex
      microencapsulation was to allow the gradual release of low molecular weight
      phagostimulants and nutrients from the cross-linked protein wall. To determine
      the release kinetics of low molecular weight compounds from the complex diet, a
      solution of the amino acid, lysine, was encapsulated in LWC and its leaching rate
      from CPWC was assessed. A batch of conventional protein-walled capsules (PWC)
      were also prepared by mixing lysine with casein. The release of lysine from CPWC
      was significantly lower than that measured from conventional PWC (p < 0.05).
      Nearly 45% of the total lysine leached out of freeze-dried PWC within 5 min of
      hydration, reaching 100% after 2 h. CPWC, on the other hand, efficiently retained
      encapsulated lysine, releasing only 25% after 2 h. In-vitro experiments indicated
      that CPWC were readily digested by the crude enzyme extract from striped bass
      larvae and purified porcine pepsin and trypsin.

PMID- 8860692
TI  - Antigenic diversity in the periodontopathogen, Actinobacillus
      actinomycetemcomitans.
AB  - We have identified a significant level of variation in antibody responses to
      Actinobacillus actinomycetemcomitans outer membrane antigens (OMA). This study
      was designed to verify A. actinomycetemcomitans antigenic diversity that could
      contribute to maintaining this chronic infection despite the host immune
      response. A. actinomycetemcomitans strains (5 from different patients and 3 the
      same patient) were cultured and OMA prepared for Western immunoblotting studies.
      Antigen bands in the OMA were identified using 7 sera obtained from 3 adult
      periodontitis (AP) and 4 localized juvenile periodontitis (LJP) patients that
      were documented with elevated A. actinomycetemcomitans antibody and infection.
      Differences/similarities in the antigen patterns among the A.
      actinomycetemcomitans strains were assessed using a kappa similarity coefficient.
      Antigen bands in the A. actinomycetemcomitans strains ranged from 11-150 kDa;
      however, variation in antigen patterns were noted among the strains. Utilizing
      the human sera as probes for antigenic diversity, the 5 heterologous strains
      showed average K=0.23 (p < 0.05), while homologous A. actinomycetemcomitans
      strains had a K=0.48 (p < 0.02). The A. actinomycetemcomitans OMA were used as
      probes to describe variability in host antibody and as such presumptive evidence
      of antigenic diversity in A. actinomycetemcomitans that is colonizing each of the
      patients. The results showed average K=0.26 (p < 0.05) for the patients when
      tested against each of the heterologous strains, and K=0.14 when tested against
      the homologous strains (p > 0.1). Finally, antigen bands of M r 80, 65, 58, 31
      and 20 kDa were demonstrated as antigens contributing to the antigenic diversity
      in A. actinomycetemcomitans.

PMID- 8860693
TI  - Rabbit complement lyses tumor cells without massive C3 deposition.
AB  - These experiments were performed to determine why rabbit complement lyses tumor
      cells very efficiently, while not having particularly strong activity in
      hemolytic assays or in any other complement assay. The target cells used were
      human tumor cells coated with three different mouse IgG(2a) monoclonal
      antibodies, and complement from 5 mammalian species were tested. In antibody
      titration experiments, rabbit complement was found to lyse target cells at a
      relatively low antibody concentration, insufficient to allow lysis by complement
      of other species. Since this result was still observed after absorption of rabbit
      serum with target cells, the potency of rabbit complement cannot be attributed to
      the presence of natural antibodies. We then assayed C3 deposition on target
      cells, using two types of (125)I-labeled anti-C3 Abs to measure C3 deposition:
      goat antibodies specific for C3 of the human, guinea pig, rabbit, rat or mouse,
      and chicken antibodies to human C3 which cross-react with C3 of other mammals.
      Unexpectedly, complement of the human, rat, guinea pig, and BUB mouse deposited
      large amounts of C3 on the surface of target cells, while rabbit complement
      deposited 100-1,000 fold less. We discuss the possible reasons that C3 deposition
      does not correlate with cytotoxicity, and may indeed be inversely related. These
      data indicate that there is a fundamental difference in the complement cascade
      between rabbits and the other species tested. The potent lytic activity of rabbit
      complement is likely to be related to this difference, although the mechanism is
      not yet understood.

PMID- 8860694
TI  - Immunomodulatory effects of IL-7 on dengue virus-specific cytotoxic CD4+ T cell
      clones.
AB  - Lymphokines play an important role in immune responses to viruses by modulating
      functions of T lymphocytes. We examined the effects of interleukin-7 (IL-7) on
      the growth and cytotoxic activity of dengue virus-specific, CD4+ human cytotoxic
      T lymphocyte (CTL) clones. We then compared the effects of IL-7 with those of
      interleukin-2 (IL-2). The CD4+CTL clones were stimulated with dengue antigen or
      monoclonal antibody to CD3 in the presence of IL-7 or IL-2. IL-7 induced the
      growth of CD4+CTL clones and maintained the antigen-specific cytotoxic activity
      without inducing antigen-non-specific cytotoxic activity. The levels of the
      growth and cytotoxic activity induced by IL-7 were similar to those induced by IL
      2. IL-7 and T-cell growth factor had an additive effect on the growth of CD4+CTL
      clones. These results suggest that IL-7 may play an important role in CD4+ T cell
      immune responses to viruses and that IL-7 is a lymphokine useful for maintaining
      the growth and antigenspecific cytotoxic activity of CD4+CTL clones in vitro,
      especially when used with T-cell growth factor.

PMID- 8860695
TI  - Peptide epitope binding specificity and V K and V H gene usage in a monoclonal
      IgM natural autoantibody to T cell receptor CDR1 from a viable motheaten mouse.
AB  - Autoantibodies (AAbs) to T cell receptor (TCR) determinants are produced in
      humans during the course of rheumatoid arthritis and systemic lupus erythematosus
      as well as in retroviral infections. We have examined the binding specificity of
      a panel of monoclonal antibodies derived from mutant viable motheaten (mev) mice
      against several TCR peptide determinants representing the complementary
      determining region 1 (CDR1) regions of various Vbeta families, and have
      identified one mAb, UN37-5, that shows high affinity binding with specificity for
      two CDR1 peptide determinants. The light and heavy chain V genes of UN37-5 were
      sequenced and compared to known V genes. The UN37-5 V H gene sequence represents
      the V H J6O6 family and is most similar to a previously reported V H gene derived
      from a germ line DNA fragment representing a unique J606 family V H gene. This
      germ line V H gene is also used by previously characterized mev derived mAbs
      directed against thymocyte and RBC antigens. The UN37-5 V L gene sequence
      represents the V K 4/5 gene family. It has 87% homology with the V K Ox-1
      germline gene. The UN37-5 V K sequence has greater than 95% identity at the amino
      acid level with VK L chains from IgM hybridomas specific for DNA and the
      influenza virus hemagglutinin. The specificity of this AAb is determined by the V
      H CDR3 and a V K chain which has not been utilized in previously reported mev
      autoantibodies.

PMID- 8860696
TI  - The tumor association of a trisaccharide epitope: specificity of antiserum
      developed to galactose beta1->3 N-acetyl glucosamine beta1-->3 galactose.
AB  - A pentasaccharide carbohydrate epitope described by Nozawa et at (1) is expressed
      by 35% of the neoplastic tissue samples from patients with endometrial cancer but
      not by normal endometrium. This epitope was detected using a human monoclonal
      antibody (HMST-1) produced by fusion of lymphocytes from an endometrial cancer
      patient. We chemically linked a synthetically produced nonreducing terminal
      trisaccharide portion of this pentasaccharide to bovine serum albumin to create
      an effective immunogen, Galbeta1->3GlcNAcbeta1->3Gal-BSA. A rabbit polyclonal
      antibody was produced and tested against panels of tumor and normal tissues. In
      contrast to the results obtained with HMST-1, 100% of the endometrial
      adenocarcinomas we studied stained with this polyclonal antiserum while normal
      endometrium was non-reactive. The reactivity with other tyes of adenocarcinomas
      was approximately 80%, whereas most normal tissues were not reactive with the
      antiserum. Immunological specificity analysis was performed with structurally
      related carbohydrates and this shows the fine specificity reaction of the
      antiserum. This antigen may be clinically useful for immunolocalization and for
      immunotargeting.

PMID- 8860697
TI  - The trauma emergency room: a concept for handling and imaging the polytrauma
      patient.
AB  - Polytrauma is a life-threatening entity that requires immediate action by all
      specialties involved. Upon arrival in the hospital, the patient will be seen and
      managed primarily by three groups of medical personnel: (a) surgeons (trauma
      specialists), (b) intensive care specialists, and (c) radiologists. The usual
      medical approach within the first minutes to hours will consist of four important
      steps: (1) primary survey, (2) resuscitation and stabilization, (3) secondary
      survey, and (4) definitive care. Survey, with regard to polytrauma, means quick
      and comprehensive evaluation of the patient's situation, clinically as well as by
      imaging. To fulfill these requirements, an interdisciplinary trauma emergency
      room with appropriate equipment, infrastructure and environment is necessary.
      Immediately after the patient's arrival and within a short time span, a limited
      number of plain radiographs of the spine, chest, pelvis, and abdomen (and
      extremities and skull, if necessary) should be obtained without turning, moving,
      or repositioning the patient. Sonography will be applied simultaneously to
      visualize or exclude: free fluid collections within the pleural spaces and/or
      peritoneal cavity and in other compartments (retroperitoneum, pelvis, soft
      tissues). Organ lesions (such as lacerations of liver, spleen or kidneys) and
      posttraumatic pathology of large vessels (tears, occlusion, aneurysm) can be
      evaluated or detected by sonography. These basic imaging studies (plain films and
      sonography) together with the clinical findings may be conclusive, or at least
      serve as decision makers for further action which may include: (a) more detailed
      plain radiography examinations, (b) tailored computed tomography examinations,
      invasive/interventional procedures (angiography or image-guided punctures), or
      (c) immediate surgical intervention. This concept is a challenge for the medical
      groups involved. Unlimited interdisciplinary cooperation and mutual exchange of
      information are the fundamental principles for successful trauma care and
      management.

PMID- 8860698
TI  - Dedicated MR system and acute trauma of the musculo-skeletal system.
AB  - MRI diffusion in the osteoarticular field is limited by the high costs of whole
      body systems. Recent technological advances have allowed the development of cost
      effective and easy-to-install dedicated MRI systems. One such system, which can
      only be employed for the study of limbs, is based on a 0.2-T permanent magnet.
      Acute trauma of the musculo-skeletal system represents an important area of
      application. Over a period of 2 years, 1258 patients with acute trauma of the
      joints (64%) and the periarticular bones (36%) have been studied. Satisfactory
      results, comparable to those from whole-body scanners operating at higher
      magnetic fields, were obtained. Acute painful syndromes did not represent an
      obstacle to the performance of the examination. Only in 2% of patients was it not
      possible to carry out the examination due to oversized limbs or complete
      articular blocks. On the basis of these considerations, it may be predicted that
      in the near future dedicated MR systems will find increasingly wide application
      in the field of musculo-skeletal traumatology.

PMID- 8860699
TI  - Wrist injuries: pitfalls in conventional imaging.
AB  - The general principles of judging wrist injuries are discussed. Carefully made
      standard views will provide recognizable projections of carpal bones in order to
      judge abnormal positions. Additional views, conventional tomography and CT scans
      are, in some instances, necessary to diagnose fractures. For ligamentous damage
      resulting in carpal instability, fluoroscopy of the wrist and/or an arthrogram
      should be obtained. Examples of difficult pathology are shown and variations or
      more or less borderline pathology as coincidental findings are discussed. The
      main pitfalls are: wrong diagnosis made on inappropriately taken radiographs;
      misinterpretation of carpal bone relationships; and overestimation of some
      arthrographically found abnormalities.

PMID- 8860700
TI  - Injuries at the articulating surfaces of bone (chondral, osteochondral,
      subchondral fractures and osteochondrosis dissecans)
AB  - Fractures involving the articulating surfaces of bone are a common cause of joint
      disability. Management options are as numerous as the terms used to describe
      these lesions. These terms include osteochondral, transchondral, flake or chip
      fractures as well as osteochondrosis (osteochondritis) dissecans. The
      understanding of these traumatic lesions and their sequelae has been increased by
      modern imaging technology, especially magnetic resonance imaging (MRI). This
      paper reviews the mechanism of these injuries, their incidence, clinical
      presentation, radiological appearance and the principles of their treatment.
      Hyaline cartilage, subchondral bone plate and subchondral cancellous bone have to
      be seen as an anatomic unity. Subchondrally located cancellous microfractures,
      osteochondral fractures and solely chondral fractures are different
      manifestations of impaction injuries at the articulating surfaces. We believe
      that osteochondrosis dissecans in most cases is also the result of undiagnosed
      injury at the articulating surface of bone.

PMID- 8860701
TI  - Whiplash injuries: is there a role for imaging?
AB  - Whiplash describes the manner in which a head is moved suddenly to produce a
      sprain in the neck and typically occurs after rear-end automobile collisions. It
      is one of the most common mechanisms of injury to the cervical spine. Although
      considered by some to be a form of compensation neurosis, evidence suggests that
      whiplash injuries are real and that they are a potential cause of significant
      impairment. Symptoms of cervical whiplash injury include neck pain and stiffness,
      interscapular pain, arm pain and/or occipital headache, and many whiplash
      patients have persistent complaints. Cervical roentgenography and conventional or
      computed tomography (CT) may show dislocations, subluxations and fractures in
      severely traumatized patients, but often fail to determine or visualize the cause
      for a whiplash syndrome. Magnetic resonance imaging (MRI), however, is able to
      assess different types of soft-tissue lesions related to whiplash injuries.
      Dynamic imaging may show functional disturbances. More widespread use of
      flexion/extension views, high-resolution static MRI and especially dynamic MRI
      should improve the correlation between imaging findings and patients' complaints.

PMID- 8860702
TI  - Normal radiographic angulation in the 4th and 5th metacarpal: a reference guide.
AB  - Accurate radiographic interpretation of deformities is of value during treatment
      of disorders of the 4th and 5th metacarpal. A uniform and simple measurement
      technique and a matching reference standard of the normal radiographic anatomy is
      indispensable to do so. Reports representing the normal radiographic angulations
      of these metacarpals are as yet not available. In 225 plain hand radiographs
      taken in PA and oblique directions, the capital- and subcapital angulations, the
      proximal articular inclination angle and the shaft bending angle, have been
      measured. A simple but effective measurement technique was developed to define
      their 'normal values'. The reproducibility of this technique was confirmed in a
      cadaver study. The obtained values were not dependent on sex, age, the involved
      side or the manual dominance. Increased subcapital inclination in one metacarpal
      was often accompanied by the same trend in the other. The values reveal some
      variation, but provide an applicable reference table. They can be used on an
      individual base for reliable determination of fracture angulation in the 4th and
      5th metacarpal in persons over 14 years old with closed growth plates.

PMID- 8860703
TI  - Survey of CT and MR imaging of the orbit.

PMID- 8860705
TI  - Imaging of the skull base.

PMID- 8860704
TI  - Paraorbital lesions.

PMID- 8860706
TI  - FDA approval of clinical studies on left ventricular assist system for its
      therapeutic application.

PMID- 8860707
TI  - Low density lipoprotein apheresis: a selective plasma separation method.

PMID- 8860708
TI  - Drug therapy of severe hypercholesterolemia in patients with coronary artery
      disease.
AB  - The beneficial effect of cholesterol-lowering therapy for secondary prevention in
      patients with coronary artery disease (CAD) is well established. The therapeutic
      goal in this situation is a low-density lipoprotein (LDL) cholesterol level of
      100 mg/dl. Cholesterol-lowering therapy will not only lead to a reduction in the
      progression of lesions but also and probably more importantly will reduce lesion
      activation and rupture and improve endothelial vasomotor function. Depending on
      the underlying hyperlipoproteinemia, the first choice for single drug therapy is
      a bile acid-binding resin or a hepatic hydroxymethyl glutaryl coenzyme A (HMG
      CoA) reductase inhibitor in isolated LDL hypercholesterolemia, and nicotinic
      acid, a fibric acid, or a HMG-CoA reductase inhibitor in combined hyperlipidemia.
      Combination therapy usually consists of a bile acid-binding resin with either an
      HMG-CoA reductase inhibitor, a fibric acid, or nicotinic acid in LDL
      hypercholesterolemia and nicotinic acid with a fibric acid in combined
      hyperlipidemia.

PMID- 8860709
TI  - State of the art of lipid apheresis.
AB  - Currently, 5 different lipid apheresis procedures are available for routine
      clinical treatment of hypercholesterolemic patients. Unselective plasma exchange
      is a technically simple extracorporeal circuit, but albumin substitution fluid
      must be used and there is no high-density lipoprotein (HDL) recovery.
      Semiselective double filtration with improved size selectivity because of a small
      pore secondary filter combines good elimination of low-density lipoprotein (LDL),
      lipoprotein (a) (Lp[a]), and fibrinogen with adequate HDL recovery; modifications
      such as thermofiltration, predilution/backflush, or pulsatile flow have been
      proposed for the improvement of this system. Three highly selective procedures
      are based on immunologic or electrostatic interactions: immunoadsorption using
      anti-low-density lipoprotein (LDL) antibodies, chemoadsorption onto dextran
      sulfate, and heparin-induced LDL precipitation (HELP) apheresis. The features of
      each system are discussed critically. Lastly, two new developments, Lp(a)
      immunoadsorption and LDL hemoperfusion using a polyacrylate LDL adsorber
      compatible with whole blood, are described.

PMID- 8860710
TI  - Evaluation of double filtration plasmapheresis, thermofiltration, and low-density
      lipoprotein adsorptive methods by crossover test in the treatment of familial
      hypercholesterolemia patients.
AB  - A comparative assessment has been made regarding efficacy and safety of the
      double filtration plasmapheresis (DFPP), thermofiltration (TFPP), and low-density
      lipoprotein (LDL) adsorptive (PA) methods by making a crossover test on
      heterozygous familial hypercholesterolemia patients. Treatments by DFPP, TFPP
      (secondary membrane Evalux 5A), and PA (Liposorber LA-40) were carried out 5
      times each, with a 2-week interval, in 5 patients with heterozygous familial
      hypercholesterolemia. The same plasma separator (Plasmacure PS-60, polysulfone)
      was used in all cases, and the volume of plasma processed was set at 4 L. High
      removal rates were obtained of total cholesterol, LDL cholesterol, triglycerides
      TG, and apolipoprotein B (apoB) by all three methods, and no differences were
      observed. Lipoprotein (a), apoA-2, apoC-3, fibrinogen, and immunoglobulin M (IgM)
      showed significantly high removal rates by the DFPP and TFPP methods compared
      with the PA method. The sieving coefficient of albumin and high-density
      lipoprotein (HDL) cholesterol at 2 and 4 L of plasma processed exhibited high
      permeabilities using all three methods. Supplementing albumin was not necessary.
      An increase of the transmembrane pressure was observed in 1 case treated by DFPP
      but was not observed when using the TFPP or PA method. No changes were observed
      in serum interleukin 1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha)
      before and after treatment by any of the three methods. No remarkable side
      effects were observed using either the DFPP or TFPP method. The DFPP and TFPP
      methods showed efficacy and safety that was not inferior to the PA method in
      conventional LDL apheresis, and the dead-end method of the filter operation
      without the discarding of plasma was shown to be possible.

PMID- 8860711
TI  - H.E.L.P. apheresis therapy in the treatment of severe hypercholesterolemia: 10
      years of clinical experience.
AB  - In collaboration with B. Braun Melsungen AG, Germany, we were able to develop the
      heparin-mediated extracorporeal low-density lipoprotein (LDL) fibrinogen
      precipitation (H.E.L.P.) system and to introduce it into clinical use. The
      H.E.L.P. apheresis system is the most potent technique to reduce at the same time
      LDL, lipoprotein (a) (Lp[a]), and fibrinogen plasma concentrations if the
      physiological clearing mechanisms are insufficient and if diet and drugs fail to
      achieve a target concentration of 100 mg/dl LDL-cholesterol or lower, required
      for secondary prevention of coronary heart disease. The H.E.L.P. LDL apheresis
      system also improves plasma viscosity and microcirculation efficiently. The
      clinical experience with the H.E.L.P. system has proved its clinical utility;
      regression of coronary heart disease occurs, a decrease in events of coronary
      heart disease takes place, and acute as well as chronic impairment of
      microcirculation shows a remarkable improvement with H.E.L.P. therapy. For the
      future, the availability of this safe and efficient apheresis technique may help
      many patients who previously could not be treated adequately.

PMID- 8860712
TI  - Short- and long-term effects on serum lipoproteins by three different techniques
      of apheresis.
AB  - Low-density lipoprotein (LDL) apheresis is applied in patients with coronary
      heart disease because of severe inherited forms of hypercholesterolemia, for
      which dietary and combined drug treatment cannot lower LDL cholesterol
      concentrations less than 130 mg/dl. The following article describes the changes
      in lipoprotein levels in a total of 19 patients undergoing weekly LDL apheresis.
      Immunoadsorption, operating with polyclonal antibodies against apolipoprotein B
      100, was used in 6 patients. Five patients were put on heparin-induced
      extracorporeal LDL precipitation (HELP) therapy; 6 received dextran sulfate
      adsorption treatments. Under steady-state conditions a single treatment reduced
      LDL cholesterol by 149 + or - 3 mg/dl with immunoadsorption, 122 + or - 2 mg/dl
      with HELP, and 124 + or - 18 mg/dl with dextran sulfate adsorption. Lipoprotein
      (a) (Lp[a]) declined by 52 to 65%. Very low density lipoprotein (VLDL)
      cholesterol and VLDL triglycerides declined by 45 to 55% because of the
      activation of lipoprotein lipase and precipitation during the HELP procedure. In
      all procedures, there was a small reduction in the different high-density
      lipoprotein fractions, which had returned to normal after 24 h. The long-term
      HDL3 cholesterol levels increased significantly. During all procedures there was
      a decrease in the molar esterification rate of lecithin cholesterol
      acyltransferase activity. All changes in lipid fractions were paralleled by
      changes in the corresponding apolipoprotein levels. It is concluded that all
      three techniques described are powerful tools capable of lowering LDL cholesterol
      in severe hereditary forms of hypercholesterolemia. In HELP and dextran sulfate
      adsorption, the amount of plasma is limited by the elimination of other plasma
      constituents. Immunoadsorption may thus be preferred in very severe forms of
      hypercholesterolemia.

PMID- 8860713
TI  - Low-density lipoprotein apheresis versus lipid lowering drugs in the treatment of
      severe hypercholesterolemia: four years' experience.
AB  - Elevated lipoprotein concentrations seem to be linked strongly in a dose
      dependent manner to an increased incidence of atherosclerosis. A total of 47
      patients suffering from severe hyperlipidemia were matched to treatment with LDL
      apheresis (Baxter, Kaneka, Lipopak; 24 patients, aged 50.2 + or - 11.5 years),
      diet, and/or lipid-lowering drugs or with diet and lipid-lowering drugs only (23
      patients, aged 48.8 + or - 11.8 years). After treatment periods of 49.8 + or -
      13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 + or - 15.1
      months (drug group), the ensuing results revealed significant differences (p <
      0.0001): -47.3% versus -12.1% for total cholesterol, -46.9% versus -21.8% for
      LDL, +8.4% versus +0.9% for HDL, -52.0% versus -13.1% for the LDL/HDL ratio, 
      36.4% versus - 16.2% for triglycerides, and -25.9% versus + 1.5% for lipoprotein
      (a). In the apheresis group, one patient died of myocardial infarction; in the
      drug group, there was one nonfatal myocardial infarction and the manifestation of
      coronary heart disease in 3 cases. There were no severe side effects in either
      group. All patients in the apheresis group responded to therapy. The present
      trial suggests that a continuing reduction in serum lipid concentrations may
      lower, in a dose dependent manner, the risk for development and progression of
      coronary heart disease. Regarding clinical and laboratory results, LDL apheresis
      seems to be safe, effective therapy for treatment of severe hyperlipidemia.

PMID- 8860729
TI  - Behavioural evidence that magnetic field effects in the land snail, Cepaea
      nemoralis, might not depend on magnetite or induced electric currents.
AB  - Although extremely low frequency (ELF) magnetic fields (<300 Hz) appear to exert
      a variety of biological effects, the magnetic field sensing/transduction
      mechanism(s) remains to be established. Here, using the inhibitory effects of
      magnetic fields on endogenous opioid peptide-mediated "analgaesic" response of
      the land snail, Cepaea nemoralis, we addressed the mechanism(s) of action of ELF
      magnetic fields. Indirect mechanisms involving both induced electric fields and
      direct magnetic field detection mechanisms (e.g., magnetite, parametric
      resonance) were evaluated. Snails were exposed to a static magnetic field (B(DC)
      = 78 +/- 1 mu T) and to a 60 Hz magnetic field (B(AC) = 299 +/- 1 mu T peak) with
      the angle between the static and 60 Hz magnetic fields varied in eight steps
      between 0 degrees and 90 degrees. At 0 degrees and 90 degrees, the magnetic field
      reduced opioid-induced analgaesia by approximately 20 percent, and this
      inhibition was increased to a maximum of 50 percent when the angle was between 50
      degrees and 70 degrees. Because B(AC) was fixed in amplitude, direction, and
      frequency, any induced electric currents would be constant independent of the
      B(AC)/B(DC) angle. Also, an energy transduction mechanism involving magnetite
      should show greatest sensitivity at 90 degrees. Therefore, the energy
      transduction mechanism probably does not involve induced electric currents or
      magnetite. Rather, our results suggest a direct magnetic field detection
      mechanism consistent with the parametric resonance model proposed by Lednev.

PMID- 8860730
TI  - Acute effects of 50 Hz magnetic field exposure on human visual task and
      cardiovascular performance.
AB  - One hundred subjects, males and females with ages ranging between 18 and 48
      years, were studied under both field-exposed and sham-exposed conditions. A 50
      Hz, 100 mu T magnetic field (MF) was used. To examine the effect of field
      exposure on performance, a two-alternative, forced-choice, duration
      discrimination task with three levels of difficulty was used. The subject's task
      was to decide which of two sequentially presented light flashes had the longer
      duration. The standard duration was 50 ms, and the alternative durations were 65,
      100, or 125 ms. Both reaction time and percentage of correct responses were
      recorded for each subject. MF and sham exposure were for 9 min each. Blood
      pressure and heart rate were also measured before and following MF exposure and
      sham-exposure trials. The study was performed double blind, with the exposure
      order counterbalanced. Compared to sham exposure, MF exposure significantly
      decreased reaction time on the hardest level of the performance task. MF exposure
      did not reliably affect percentage correct or cardiovascular performance. It was
      demonstrated that a relatively high level of statistical power was the basis for
      the observed MF effect, and the need to pay closer attention to power levels in
      future research is discussed.

PMID- 8860731
TI  - Evaluating alternative exposure indices in epidemiologic studies on extremely low
      frequency magnetic fields.
AB  - Choosing the right exposure index for epidemiological studies on 50-60 Hz
      magnetic fields is difficult due to the lack of knowledge about critical exposure
      parameters for the biological effects of magnetic fields. This paper uses data
      from a previously published epidemiological investigation on early pregnancy loss
      (EPL) to study the methods of evaluating the exposure-response relationship of 50
      Hz magnetic fields. Two approaches were used. The first approach was to apply
      generalized additive modeling to suggest the functional form of the relationship
      between EPL and magnetic field strength. The second approach evaluated the
      goodness of fit of the EPL data with eight alternative exposure indices: the 24 h
      average of magnetic field strength, three indices measuring the proportion of
      time above specified thresholds, and four indices measuring the proportion of
      time within specified intensity windows. Because the original exposure data
      included only spot measurements, estimates for the selected exposure indices were
      calculated indirectly from the spot measurements using empirical nonlinear
      equations derived from 24 h recordings in 60 residences. The results did not
      support intensity windows, and a threshold-type dependence on field strength
      appeared to be more plausible than a linear relationship. In addition, the study
      produced data suggesting that spot measurements may be used as surrogates for
      other exposure indices besides the time average field strength. No final
      conclusions should be drawn from this study alone, but we hope that this exercise
      stimulates evaluation of alternative exposure indices in other planned and
      ongoing epidemiological studies.

PMID- 8860732
TI  - Calcium homeostasis of isolated heart muscle cells exposed to pulsed high
      frequency electromagnetic fields.
AB  - The intracellular calcium concentration ([Ca(2+)]i) of isolated ventricular
      cardiac myocytes of the guinea pig was measured during the application of pulsed
      high-frequency electromagnetic fields. The high-frequency fields were applied in
      a transverse electromagnetic cell designed to allow microscopic observation of
      the myocytes during the presence of the high-frequency fields. The [Ca(2+)]i was
      measured as fura-2 fluorescence by means of digital image analysis. Both the
      carrier frequency and the square-wave pulse-modulation pattern were varied during
      the experiments (carrier frequencies: 900, 1,300, and 1,800 MHz pulse modulated
      at 217Hz with 14 percent duty cycle; pulsation pattern at 900 MHz: continuous
      wave, 16 Hz, and 50 Hz modulation with 50 percent duty cycle and 30 kHz
      modulation with 80 percent duty cycle). The mean specific absorption rate (SAR)
      values in the solution were within one order of magnitude of 1 mW/kg. They varied
      depending on the applied carrier frequency and pulse pattern. The experiments
      were designed in three phases: 500 s of sham exposure, followed by 500 s of field
      exposure, then chemical stimulation without field. The chemical stimulation (K+ 
      depolarization) indicated the viability of the cells. The K+ depolarization
      yielded a significant increase in [Ca(2+)]i. Significant differences between sham
      exposure and high-frequency field exposure were not found except when a very
      small but statistically significant difference was detected in the case of 900
      MHz/50 Hz. However, this small difference was not regarded as a relevant effect
      of the exposure.

PMID- 8860733
TI  - Effects of 60 Hz electromagnetic fields on early growth in three plant species
      and a replication of previous results.
AB  - In an attempt to replicate the findings of Smith et al., seeds of Raphanus
      sativus L. (radish), Sinapsis alba L. (mustard), and Hordeum vulgare L. (barley)
      were grown for between 9 and 21 days in continuous electromagnetic fields (EMFs)
      at "ion-cyclotron resonance" conditions for stimulation of Ca(2+) (B(H) = 78.3 mu
      T, B(HAC) = 40 mu T peak-peak at 60 Hz, B(V) = 0). On harvesting, radish showed
      results similar to those of Smith et al. Dry stem weight and plant height were
      both significantly greater (Mann-Whitney tests, Ps < 0.05) in EMF-exposed plants
      than in control plants in each EMF experiment. Wet root weight was significantly
      greater in EMF-exposed plants in two out of three experiments, as were dry leaf
      weight, dry whole weight, and stem diameter. Dry root weight, wet leaf weight,
      and wet whole weight were significantly greater in EMF-exposed plants in one of
      three experiments. All significant differences indicated an increase in weight or
      size in the EMF-exposed plants. In each of the sham experiments, no differences
      between exposed and control plants were evident. Mustard plants failed to respond
      to the EMFs in any of the plant parameters measured. In one experiment, barley
      similarly failed to respond; but in another showed significantly greater wet root
      weight and significantly smaller stem diameter and dry seed weight at the end of
      the experiment in exposed plants compared to control plants. Although these
      results give no clue about the underlying bioelectromagnetic mechanism, they
      demonstrate that, at least for one EMF-sensitive biosystem, results can be
      independently replicated in another laboratory. Such replication is crucial in
      establishing the validity of bioelectromagnetic science.

PMID- 8860734
TI  - Brief communication: coaxial lines for multiphase power distribution.
AB  - A coaxial cable can be used to reduce the magnetic and electric fields that
      extend into environments in the vicinity of transmission lines and distribution
      lines and in-house or building wiring for power distribution systems. The use of
      the coaxial geometry may prove useful in cases where there are environmental
      concerns with respect to health effects and in cases where there is a need to run
      high-speed data communications in close proximity to power distribution systems.

PMID- 8860736
TI  - Distinctive ultrastructural pathology of nonulcerative interstitial cystitis: new
      observations and their potential significance in pathogenesis.
AB  - Ultrastructural study of the bladder in interstitial cystitis has, so far, been
      limited, mainly to the urothelium. The present study was conducted first to study
      in detail the ultrastructural features of all tissue components of the bladder
      wall in nonulcerative interstitial cystitis and second to derive clues from the
      observed changes to pathogenesis of the disease. Endoscopic biopsies of
      urothelium with attached suburothelium, and muscularis, were obtained from both
      lesional and nonlesional areas in 5 female patients with unequivocal clinical
      diagnosis of interstitial cystitis. The specimens were processed for electron
      microscopic study by standard methods and subjected to comprehensive
      ultrastructural study of urothelium, suburothelium, detrusor muscle cells,
      intrinsic blood vessels, and intrinsic nerves. A distinctive combination of
      peculiar muscle cell profiles, injury of intrinsic vessels and nerves in
      muscularis and suburothelium, and discohesive urothelium was observed in lesional
      and less markedly in nonlesional samples of all specimens. Marked edema of
      various tissue elements and cells appeared to be a common denominator of many
      observed changes. Edema of muscle cells resulted in characteristic querciphylloid
      profiles, so designated because of peripheral bosselation of cell sarcoplasm with
      a lobed perimeter resembling that of an oak leaf. Urothelial changes disrupted
      the true permeability barrier, consisting of asymmetric unit membrane and triple
      epithelial junctions of surface (umbrella) cells. Vascular lesions included
      endothelial cell injury and suggested sluggishness of intrinsic microcirculation.
      Neural changes included a combination of degenerative and regenerative features,
      some expressing neural plasticity. The observed ultrastructural changes appear to
      be sufficiently distinctive to be diagnostic in specimens submitted for
      pathologic confirmation of nonulcerative interstitial cystitis. The changes do
      not support a primary pathogenetic role of mast cells or a selectively deficient
      glycosaminoglycan layer. They do suggest, however, a pathogenesis based on a
      potentially self-perpetuating process of neurogenic inflammation that can trigger
      a biologically potent cascade of events, including a leaky urothelium and mast
      cell activation. As proposed, neurogenic inflammation consolidates various
      proposals advanced as the pathogenesis of interstitial cystitis and can readily
      accommodate infectious, immunologic, and autoimmunologic mechanisms as factors
      that contribute to development or chronicity of the disease.

PMID- 8860737
TI  - Comparison of ureteropelvic transitional cell carcinoma with bladder transitional
      cell carcinoma using an image analyzer.
AB  - To elucidate whether a significant difference in malignant potential between
      ureteropelvic transitional cell carcinoma (TCC) and bladder TCC is present, the
      argyrophilic nucleolar organizer region (AgNOR), nuclear DNA content and mean
      nuclear area (MNA) were evaluated in 32 ureteropelvic TCCs and 60 bladder TCCs,
      and were also compared with histological grade and stage. The parameters used
      were the mean AgNOR count (C-AgNOR), the percentage of cells exhibiting more than
      3 AgNOR dots within nuclei (P-AgNOR), 2c deviation index (2cDI), 5c exceeding
      rate (5cER) and MNA. No significant difference in these 5 parameters was found
      between ureteropelvic and bladder TCCs. In addition, within each histological
      grade of tumor, no significant difference in each parameter between ureteropelvic
      and bladder TCCs was noted. Similarly, within pTa or pT1 TCCs, there was no
      significant difference in the parameters between ureteropelvic and bladder TCCs.
      On the other hand, invasive TCCs (pT2 and higher), the C-AgNOR and P-AgNOR were
      significantly higher in ureteropelvic than in bladder TCC (p < 0.05), while no
      significant difference in 2cDI, 5cFR and MNA was noted. These findings suggest
      that: (i) as a whole, the difference in malignant potential between ureteropelvic
      and bladder TCCs appears to be less significant, and (ii) factors other than the
      malignant potential of a tumor might contribute to the unfavorable clinical
      outcome in patients with ureteropelvic TCC.

PMID- 8860738
TI  - Prostate-specific antigen as a marker of bone metastasis in patients with
      prostate cancer.
AB  - OBJECTIVE: Staging in patients with newly diagnosed untreated cancer of the
      prostate has significant ramifications on the management of the disease.
      Currently measurement of the serum prostate-specific antigen (PSA) concentration
      and radionuclide bone scan are two important procedures in the metastatic workup
      of these patients. We retrospectively evaluated the efficacy of PSA as a staging
      marker to discriminate prostate cancer patients with bone metastases from those
      without bone metastases. MATERIALS AND METHODS: In a retrospective study 158
      prostate cancer patients with (n = 21) and without (n = 137) bone metastases were
      analyzed. In all patients the initial PSA measurement as well as the radionuclide
      bone scan were evaluated. RESULTS: Patients with bone metastases demonstrated a
      median serum PSA concentration of 151 ng/ml and only 1 patient revealed a serum
      PSA concentration of <10 ng/ml. This resulted in a negative predictive value of
      98%. In addition 67% of these patients demonstrated a serum PSA concentration of
      >100 ng/ml, which resulted in a positive predictive value of 74% and an overall
      accuracy of 92%. CONCLUSION: The serum PSA concentration seems to provide useful
      information with regard to the presence of bone metastasis in patients with newly
      diagnosed cancer of the prostate. A serum PSA value of <10 ng/ml nearly excludes
      bone metastases, whereas a serum PSA value of> 100 ng/ml is highly predictive of
      bone metastases.

PMID- 8860739
TI  - Urinary 28-kD calbindin-D as a new marker for damage to distal renal tubules
      caused by cisplatin-based chemotherapy.
AB  - Calbindin-D, a vitamin D-dependent calcium-binding protein of 28 kD, is found
      predominantly in the distal tubules of the kidney and central nervous system
      tissues in humans. To evaluate damage to the renal tubules caused by cisplatin
      based chemotherapy, levels of urinary and serum calbindin-D were determined in
      patients treated with cisplatin- or carboplatin-based chemotherapies using a
      highly sensitive enzyme immunoassay system developed in our laboratory. Levels of
      urinary 28-kD calbindin-D were also determined in patients with benign and
      malignant urological diseases. The mean urinary calbindin-D level was 2.44 + or -
      0.31 (mean + or - SE) ng/mg creatinine in 40 healthy subjects. Urinary calbindin
      D levels were elevated (>10 ng/mg creatinine) in 2 of 33 patients (6%) with
      benign and 1 of 50 (2%) with malignant urological diseases. Urinary calbindin-D
      levels were significantly increased after cisplatin-based chemotherapy in 14
      patients, with peaks (71.8 + or - 13.5 ng/mg creatinine) being found 8 days after
      administration of cisplatin, and then a gradual return to the baseline. On the
      other hand, 7 patients receiving carboplatin-based chemotherapy demonstrated no
      significant elevation (highest level 7.7 + or - 2.5 ng/mg creatinine). In 7
      patients treated with cisplatin-based chemotherapy the serum calbindin-D level
      was also raised after treatment, with a good correlation to urinary values. These
      findings suggest that urinary and serum calbindin-D may be kidney-derived and
      that 28-kDa calbindin-D is a useful marker for damage to the distal renal tubules
      associated with cisplatin-based chemotherapy.

PMID- 8860740
TI  - Cystine stones: the efficacy of percutaneous and shock wave lithotripsy.
AB  - Cystinuria is a rare cause of renal calculi, whose management presents a complex
      problem mainly due to the hardness and high recurrence rate of cystine stones.
      During the period 1987-1991, 28 established cases of cystine calculi were treated
      by extracorporeal shock wave lithotripsy (ESWL) and percutaneous
      nephrolithotripsy (PCNL). These cases were divided into 5 groups, according to
      the position and size of the stones, and each group then followed a specific
      regimen, either ESWL monotherapy or a combined treatment comprising an initial
      ESWL treatment followed by PCNL or vice versa. ESWL monotherapy provided
      satisfactory results only in the group with pelvic stones (54.5% success rate),
      with 2.16 stone treatments/renal unit, and only with calculi smaller than 2.5 cm.
      The groups with multiple stones or staghorn calculi were treated with a combined
      treatment of ESWL and PCNL and had success rates of 50 and 67%, respectively.
      However, the group in which PCNL was followed by ESWL showed a clear advantage
      over the group in which ESWL was administered before PCNL, since it required a
      smaller number of ESWL treatments (1,5 stone treatments/renal unit as compared to
      4.3 stone treatments/renal unit). Finally, attempts for ESWL in situ in the few
      cases of ureteral stones proved unsuccessful.

PMID- 8860741
TI  - Color-coded Doppler sonography in the diagnosis of abdominal masses.
AB  - A man in his forties was operated on for testicular cancer on the right-side with
      subsequent radiotherapy. Two years later, another tumor was found on the opposite
      side and surgically removed, followed by polychemotherapy. In the follow-up
      period, CT scanning and ultrasound showed large abdominal masses which were
      suspected to be metastases. Before initiating four cycles of chemotherapy, we
      checked their nature by Doppler sonography and found them to be recently
      developed abdominal varices due to an alcoholic liver cirrhosis. We were able to
      demonstrate that Doppler sonography can provide further information and is easy
      to use.

PMID- 8860742
TI  - Spontaneous hemorrhage during pregnancy secondary to renal angiomyolipoma.
AB  - We report a case of spontaneous hemorrhage secondary to renal angiomyolipoma
      treated with percutaneous transcatheter arterial embolization. Fourteen and 18
      months after the procedure, the patient showed repeated spontaneous hemorrhage
      during pregnancy. However, a healthy female infant was delivered at the 39th week
      of the pregnancy. We discuss the management of renal angiomyolipoma in young
      married women before pregnancy.

PMID- 8860743
TI  - Primary renal lymphoma. Case report and review of the literature.
AB  - Primary renal lymphoma is not well recognized, although secondary renal
      involvement from systemic lymphoma is common. A case of non-Hodgkin's B-cell-type
      malignant lymphoma in the kidney is reported, and a review of the literature on
      primary renal lymphoma is made.

PMID- 8860744
TI  - Synchronous bilateral carcinoma of the ureter in association with unilateral
      incomplete duplication of the ureter.
AB  - A case of bilateral synchronous ureteral tumors, in association with a unilateral
      incomplete duplication of ureter, is presented. This patient underwent right
      nephroureterectomy with removal of a cuff of bladder, partial resection of left
      ureter, and ileal loop interposition between renal pelvis and bladder. Followup
      showed no recurrence in the residual urinary tract 2-years postoperatively.

PMID- 8860745
TI  - Excessive testosterone production in a patient with Nelson syndrome and bilateral
      testicular tumors.
AB  - Bilateral primary testicular tumors are rare and usually consist of either
      interstitial cells or hypertrophic testicular adrenal remnant tissue. Their
      differentiation on clinical presentation and histologic examination remains
      difficult but is essential because of the different therapeutic approaches. We
      report a rare case of excessive testosterone production by bilateral testicular
      tumors in a patient with Nelson syndrome (ACTH-secreting pituitary adenoma after
      bilateral adrenalectomy in patients with Cushing's disease). Increased ACTH
      stimulation in this patient supports the thesis of pluripotent cells within the
      testis which can undergo differentiation to cells which are not only
      morphologically similar to Leydig cells but also have the functional property of
      these cells. Our clinical findings support the diagnosis of hyperplasia of
      adrenal remnant or pluripotent cells rather than a true Leydig cell tumor. We
      emphasize the need for hormonal evaluations which should be assessed in the
      context of the size of these nodular tumors prior to therapeutic decisions. In
      cases with elevated serum ACTH and small nodular hyperplasia, we would favor a
      'wait-and-see' strategy with appropriate hormonal therapy. In large tumors with
      clinical signs of hormonal activity, patient noncompliance with steroid
      replacement regimens or with local symptoms, scrotal exploration and tumor
      enucleation are indicated.

PMID- 8860746
TI  - Infertility as the first symptom of male genitourinary tuberculosis.
AB  - The diagnosis of male genitourinary tuberculosis is seldom apparent until the
      disease is far advanced. The earliest clinical symptoms in most cases are
      epididymitis, dysuria, and hematuria. In the present case, evaluation of a 26
      year-old male complaining about primary infertility revealed leukocytospermia and
      a normal sperm count. The diagnosis of genitourinary tuberculosis was based on
      positive morning urine culture. Infertility is an uncommon first sign of male
      genitourinary tuberculosis, but may be a clue to early diagnosis, as demonstrated
      in the present case.

PMID- 8860747
TI  - Youth at risk: definitions and implications for service delivery.
AB  - The literature on adolescent risk is reviewed, a model of risk that emphasizes
      risk antecedents and markers is proposed, and an overview is presented of an
      emergency service delivery strategy that integrates services, emphasizes
      interagency coordination, and addresses the full range of service needs for youth
      at risk. Highlights of programs currently in operation are described.

PMID- 8860757
TI  - Casual attributions about mental illness: relationship to family functioning.
AB  - The relationship between causal attributions about mental illness and family
      functioning was investigated in 39 individuals with chronic mental illness and
      their families. Among parents and siblings, poor family functioning was
      associated with attribution to a person as the cause of the illness.
      Unexpectedly, no relationship was found between family functioning and causal
      attributions to genetics, biology, God, or chance.

PMID- 8860758
TI  - Obsessive-compulsive disorder: effects on family members.
AB  - A study of 225 family members of individuals with obsessive-compulsive disorder
      explored the greatest concerns of family members, examining the extent to which
      they found different kinds of OCD-linked behavior disturbing, and various
      resources helpful. Services to enhance family functioning are discussed.

PMID- 8860759
TI  - Substitute child care at different ages: relationship to social-emotional
      functioning in preschool.
AB  - In a pilot study based on parent and teacher ratings, the number of hours spent
      in substitute care during the first three years of life correlated with
      children's levels of behavior problems in preschool. The developmental period
      from 18 to 24 months was the most sensitive to the use of substitute care, and
      boys were more negatively affected than girls. The child-adult ratio and setting
      were not significant factors. Results suggest reconsideration of parental leave
      policies and direction for future research.

PMID- 8860760
TI  - Allergic fungal sinusitis with cranial base erosion.
AB  - BACKGROUND: Allergic fungal sinusitis (AFS) usually follows a slow, nonaggressive
      course. However, massive bone destruction can occur, with extension of the
      disease process outside of the confines of the sinuses. METHODS: Our series of 28
      cases of AFS was reviewed. We identified 6 cases of AFS with definite
      radiographic evidence of skull base erosion. RESULTS: Histologic diagnostic
      criteria for AFS were present in all 6 cases. All patients were managed with
      surgery, most recently conservative endoscopic surgery. An earlier patient
      underwent dural resection. Antibiotics were used in all patients, but no
      antifungal agents were administered. No patient has had a permanent neurologic
      complication, although one was seen with abducens palsy. There have been no
      cerebrospinal fluid (CSF) leaks. All 6 cases also had orbital bone erosion, but
      none has had permanent ophthalmologic sequelae. All patients were initially
      suspected to have a neoplastic disease. CONCLUSIONS: We propose a new diagnostic
      entity, "skull base allergic fungal sinusitis" (SBAFS), which incorporates the
      histologic diagnostic criteria of AFS with the computed tomographic (CT) criteria
      of bone erosion. Biopsy is necessary to rule out invasive fungus or tumor.
      Otolaryngologists, ophthalmologists, and neurosurgeons should be familiar with
      SBAFS so that systemic antifungal agents, craniotomy, and dural resection-which
      might initially appear necessary-can be avoided. Endoscopic surgical debridement
      and drainage combined with topical steroids can lead to resolution of disease,
      even in the presence of marked bone erosion and cranial neuropathy.

PMID- 8860761
TI  - Blood transfusions in laryngeal cancer: effect on prognosis.
AB  - METHODS: To evaluate the influence of homologous perioperative transfusion on
      oncologic control and survival in patients with larynx and hypopharynx
      carcinomas, we conducted a retrospective study of 269 patients with larynx and
      hypopharynx carcinoma treated by major surgical procedures. A total of 20
      variables were analyzed for each patient. RESULTS: Perioperative transfusion was
      required in 86 (32%) patients, with packed red blood cells being used in all
      cases. Recurrence at a local, regional, or distant level was 31% for
      nontransfused and 35% for transfused patients. The 5-year adjusted survival was
      68% for patients without transfusion and 63% for patients with transfusion.
      Neither the univariate nor the multivariate analysis showed that perioperative
      transfusion or the number of units of packed red blood cells used had any
      prognostic capacity. CONCLUSIONS: Homologous perioperative transfusion did not
      imply a significant risk regarding global control or survival in our larynx or
      hypopharynx cancer patients.

PMID- 8860762
TI  - Carcinoma in situ of the glottic larynx: excision or irradiation?
AB  - BACKGROUND: The management of glottic carcinoma in situ (CIS) is controversial,
      with vocal cord stripping (S) generally accepted as the standard treatment, and
      radiotherapy (RT) as an alternative. We present our experience with 34 patients
      treated by either stripping or RT. METHODS: ++Between 1974 and 1990, 34 patients
      with CIS of the glottic larynx larynx were treated at McGill University teaching
      hospitals. The median age at diagnosis was 67 years, with a male:female ratio of
      6:1. All patients had CIS involving the glottis and the pathology was reviewed on
      all patients. Twenty-one patients were treated by S and 13 patients by RT as the
      primary treatment. RESULTS: With a median follow-up of 96 months (25-209 months),
      the 15-year actuarial survival rate is 95% for all patients, with 100% and 87%
      survival rates for S and RT groups, respectively (p = 0.25). One patient in the
      RT group developed a subglottic invasive squamous cell carcinoma. On the other
      hand, 11 patients in the S group developed recurrence and were treated by repeat
      S (6 patients) or RT (5 patients), with a salvage rate of 100%. CONCLUSION:
      Although most patients with CIS of the glottis are traditionally treated with
      vocal cord S, RT is effective in terms of freedom from recurrence; it is an
      attractive option and should be considered in patients with lesions recurring
      after stripping as well as in those whose follow-up presents a problem.

PMID- 8860763
TI  - Salvage surgery after radiotherapy failure in T1-T2 squamous cell carcinoma of
      the glottic larynx.
AB  - BACKGROUND: This study was undertaken to analyze the clinical course of patients
      who developed local (primary) recurrence after high-dose irradiation of T1 -T2
      squamous cell carcinoma of the glottic larynx. METHODS: Between May 1977 and
      December 1989, 247 patients with previously untreated T1 and T2 invasive squamous
      cell carcinoma of the glottic larynx were treated for curative intent with
      radiotherapy. Local recurrence occurred in 26 of 247 patients (11%). Successful
      surgical salvage was defined as no evidence of recurrent cancer for at least 2
      years after salvage surgery and continuously thereafter. RESULTS: Two patients
      refused to undergo salvage surgery and one patient had unresectable disease. Of
      23 patients who underwent salvage surgery, 19 had a total laryngectomy and 4 had
      a voice-sparing procedure. One patient who was continuously free of disease, died
      less than 24 months after salvage surgery; this patient was excluded from all
      local control and survival analyses, leaving 22 patients available for analysis.
      Successful salvage was achieved initially in 13 (59%) of the 22 patients. Two
      patients with local failure after voice-sparing salvage surgery underwent
      completion laryngectomy; one was salvaged, so that 14 of 22 (64%) were ultimately
      salvaged. The rate of successful salvage did not correlate with preirradiation T
      stage, time to failure after irradiation, or time from clinical suspicion of
      recurrence to histologic proof. In a subgroup of patients (those with positive
      margins, tumor extension into the soft tissues of the neck, or two or more
      adverse histologic features), the risk of local-regional recurrence after salvage
      laryngectomy was 80%. CONCLUSION: There are few data in the literature regarding
      the clinical outcome of patients whose tumors are not controlled by initial
      radiotherapy. This series and previous publications from other institutions
      indicate that most patients who develop primary failure undergo salvage surgery,
      which is successful in approximately 50-80% of the patients. The rate of surgical
      complications is acceptable and is related to radiotherapy dose. At our
      institution, most patients who had recurrence after radiotherapy underwent total
      laryngectomy. More than 50% of the patients who experienced recurrence after
      irradiation originally had tumors of such extent that they would have required
      total laryngectomy if surgery had been recommended instead of radiotherapy for
      the initial treatment. It is reasonable to consider reirradiation in patients
      with a very high risk of local-regional recurrence after salvage laryngectomy.

PMID- 8860764
TI  - Neurotoxicity in a phase I trial of continuous infusion cisplatin with
      hyperfractionated radiotherapy for locally advanced head and neck cancer.
AB  - BACKGROUND: Both twice daily fractionated radiotherapy and concurrent cisplatin
      with once-daily radiotherapy have been shown to improve local disease control in
      patients with head and neck cancer. The objective of this phase I trial was to
      determine the maximum tolerated dose of cisplatin which could be given as a
      continuous infusion concurrent with twice-daily radiotherapy to patients with
      locally advanced head and neck cancer. METHODS: Patients were treated with
      radiotherapy at doses of 110 cGy twice daily for 5 days per week to a total dose
      of 7040-7590 cGy. Concurrent with radiotherapy, patients received continuous
      infusion cisplatin for 5 days per week. Groups of 3-6 patients were treated with
      doses of 1-3 mg/m2/day. RESULTS: Central nervous system toxicity became dose
      limiting. At 1 mg/m2, 2 mg/m2, and 3 mg/m2 confusion was observed and one patient
      had a seizure. At 3 mg/m2, another patient suffered severe sensory and motor
      neuropathy. Despite bulky tumors, 12 of the 14 patients had an objective response
      and 3 achieved a complete response. CONCLUSION: the combination of twice-daily
      fractionated radiotherapy and concurrent cisplatin by continuous infusion is
      severely toxic and achieves results similar to less toxic programs. It is not
      recommended for further investigation or therapy.

PMID- 8860765
TI  - Whole salivary flow rates following submandibular gland resection.
AB  - BACKGROUND: Patients with head and neck neoplasms receive therapeutic neck
      dissections which may include the submandibular gland unilaterally or
      bilaterally. The clinical consequences of salivary gland resection could be
      reduced salivary output, altered cariogenic microflora, and increased incidence
      of dental caries. METHODS: This investigation evaluated whole salivary flow rates
      of patients who had received unilateral (n = 29) or bilateral (n = 8)
      submandibular gland resections and compared them with noncancer control subjects
      (n = 29). RESULTS: Unstimulated and stimulated (paraffin) flow rates were
      significantly lower in both resection groups compared with those of the noncancer
      group, ranging from p < .002 to p < .02. Although flow rates were lower in the
      bilateral group than in the unilateral group, the differences between these two
      groups were statistically significant (p < .02) only for stimulated saliva.
      Xerostomia was reported by one third of the resection subjects. CONCLUSION: In
      view of the significantly lower flow rates observed in the resection groups
      (especially for unstimulated saliva), topical fluoride therapy should be
      considered for those patients whose past caries activity would indicate an
      increased caries risk associated with partial loss of salivary function.

PMID- 8860766
TI  - Loss of heterozygosity studies in squamous cell carcinomas of the head and neck.
AB  - BACKGROUND: Loss of heterozygosity (LOH) studies have been pivotal in identifying
      tumor suppressor genes involved in the pathogenesis of a number of cancers. In
      squamous cell carcinomas of the head and neck region (SCCHN), LOH studies using
      the Southern blot technique are scarce. METHODS: SCCHNs were obtained immediately
      after surgical resection from 78 patients. Histologic confirmation was made by
      frozen section and tumors with less than 50% malignant cells were excluded. DNA
      was digested with restriction enzymes, and after Southern blotting the membranes
      were hybridized with radio-labeled probes. Chromosome arms analyzed included 1p,
      3p, 4p, Sq, 8p, lOp, 11p, 11q, 13q, 17p, 17q, 18q, 21q, and 22q. RESULTS: The
      average rate LOH was 25% per chromosome arm. Significantly higher rates of LOH
      were observed for chromosome arms 5q (56%) and 17p (45%). Other investigators
      have reported high rates of LOH for the H- ras-1 locus, and chromosome arms 11p,
      11q, and 13q. However, these results were not confirmed in this study. For
      patients with stage 1 or 2 tumors, the overall LOH rate was 13%, and for patients
      with stage 3 or 4 disease the rate was 23%. This difference was statistically
      significant (p < 0.025). CONCLUSIONS: tumors progress to higher stages, they
      appear to accumulate an increasing number of genetic abnormalities. Chromosome
      arms 5q and 17p contain tumor suppressor genes which are likely to be involved in
      the pathogenesis of SCCHN:

PMID- 8860767
TI  - Motor innervation of the trapezius muscle: a histochemical study.
AB  - BACKGROUND: Controversy exists as to the significance of the cervical plexus as
      efferent to the trapezius muscle. We have sought to further study this question
      and to add to anatomic and electrophysiologic evidence of a histochemical
      perspective. METHOD: The accessory nerve and the cervical plexus branches from 18
      neck dissections were studied by histochemical staining for acetylcholinesterase
      (motor nerve) and carbonic anhydrase (sensory nerve) activity. The motor controls
      were either accessory nerve, ansa hypoglossi or hypoglossal nerve, and for
      sensory controls the greater auricular nerve. RESULTS: Eleven of 18 necks (61%)
      contained evidence of motor axons in the branches of the cervical plexus. Motor
      axons were noted mainly in C3 and or C4. CONCLUSION: There is confirmatory
      histochemical evidence that a significant proportion of cervical spinal nerves to
      the accessory nerve or trapezius contain motor nerves.

PMID- 8860768
TI  - T stage and functional outcome in oral and oropharyngeal cancer patients.
AB  - BACKGROUND: The locus and extent of resection and the type of reconstruction used
      in surgery are important joint determinants of functional outcome in oral and
      oropharyngeal cancer patients. However, prediction of functional outcome from
      broader factors such as clinical T stage and approximate locus of resection is
      important for the preoperative period when the extent of resection and the exact
      surgical reconstruction to be used may not be decided and preoperative counseling
      about potential functional outcomes is needed. METHODS: Oropharyngeal swallow
      efficiency (OPSE) and conversational speech understandability (CU) were measured
      preoperatively and 3 months posthealing in 68 patients. Analysis of variance
      (ANOVA) was used to determine whether clinical T stage and planned surgical locus
      were significantly related to these two functional measures, and discriminant
      analysis was used on the data obtained at 3 months to determine how well CU and
      liquid OPSE jointly relate to the T stages. RESULTS: In patients with a planned
      oral tongue locus of resection, significant differences were found at 3 months
      posthealing on both CU and liquid OPSE between stages T1 -T2 and T3 and between
      T1-T2 and T4. In patients with a planned oropharynx locus of resection,
      significant differences were found only on CU at 3 months. These occurred between
      T1-T2 and T4 and between T3 and T4. Discriminant analysis classified into the
      correct T stages 70% of T1-T2 and 75% of T4 stage patients, but only 28% of T3
      stage patients. However, the T3-stage patients who were misclassified as T4 had
      significantly larger mean percent of oral tongue resected than those T3 stage
      patients who were misclassified as T1-T2. CONCLUSIONS: These results are useful
      for the preoperative counseling of patients with clinical T stages 1-2 and 4. The
      relationship between T stage and postsurgical function found here is stronger
      than reported by previous authors, but is still very general.

PMID- 8860769
TI  - Relationship between psychological status and compliance in a sample of patients
      treated for cancer of the head and neck.
AB  - BACKGROUND: the psychological status of patients treated for advanced head and
      neck cancer is an area of patient care that has not received sufficient attention
      from caregivers and can be influential in terms of patient outcomes. METHODS:
      Thirty patients participated in this study designed to evaluate areas of
      psychological distress associated with treatment of advanced head and neck
      cancer. Patients completed a set of questionnaires related to various
      psychosocial variables including anxiety, depression, social support, health
      locus of control, adjustment to illness, illness-related behaviors, and
      compliance. RESULTS: Moderate levels of depression and anxiety, disability, and
      psychological distress characterize this sample of patients. Additionally,
      patient self-report of compliance reveals different variable combinations to be
      related to overall diet and medication compliance, and different levels of each
      compliance type were observed. CONCLUSION: Head and neck cancer therapy presents
      a unique set of challenges for patients. Awareness of the impact of the illness
      and the psychological distress that are experienced should improve patient
      compliance and medical outcome.

PMID- 8860770
TI  - Preservation of function by radiotherapy of small primary carcinomas preceded by
      neck dissection for extensive nodal metastases of the head and neck.
AB  - BACKGROUND: When patients are initially seen with a small primary tumor and
      regional metastases, the question arises whether the primary can be managed by
      definitive radiotherapy while treating the neck with surgery and postoperative
      radiation. The advantage of this is least disturbance of the primary site, while
      still achieving maximal control of the neck disease. METHOD: A retrospective
      review was conducted over an 8-year period; of the 619 patients seen during this
      time, 15 were judged suitable for this approach. Small primaries were defined as
      T1 or T2 lesions or superficial spreading T3 tumors. Extensive neck disease was
      defined as at least 3 cm in size. RESULTS: There were no regional recurrences and
      only 3 local recurrences, 2 of which were successfully salvaged. Four patients
      died of distant metastases. The arguments for and against this unusual approach
      are discussed. CONCLUSIONS: It is concluded that, in patients conforming to our
      criteria, this is a sound oncologic approach.

PMID- 8860771
TI  - Tumor angiogenesis.
AB  - BACKGROUND: The growth of solid tumors, including head and neck squamous cell
      carcinomas, depends on the establishment of a blood supply within the tumor
      (neovascularization or angiogenesis). For this process to take place, tumors
      produce growth factors which stimulate the proliferation, migration, and
      differentiation of endothelial cells. These growth factors are polypeptides that
      preferentially bind heparan sulfate. In several tumor systems, the degree of
      angiogenesis can be correlated with tumor aggressiveness and clinical outcome.
      RESULTS: Head and neck squamous cell carcinomas produce an angiogenic response in
      the chick embryo chorioallantoic membrane assay. Additionally, supernatants from
      head and neck squamous cell carcinoma lines enhance endothelial cell
      proliferation and stimulate adhesion of endothelial cells to elements of the
      connective tissue matrix. CONCLUSIONS: Experimental evidence appears to
      demonstrate the angiogenic capacity of head and neck squamous cell carcinomas in
      vivo. Additionally, data from several laboratories have demonstrated that head
      and neck carcinomas produce several endothelial cell mitogens and chemotactic
      factors. Clinical pathologic studies correlating angiogenesis of head and neck
      carcinomas with node metastasis, survival, and recurrence rate are conflicting.
      Current studies are underway to more clearly define the mechanism(s) of
      angiogenesis induced by head and neck cancers.

PMID- 8860772
TI  - Wide reconstruction of the anterior cranial base with bipedicled galeopericranial
      flap.
AB  - BACKGROUND: Reconstruction of facial bone fractures complicated by frontal sinus
      destruction must seal off the cranial cavity from the upper respiratory tract to
      avoid ascending infections of the intracranial contents. METHODS: We used a
      bipedicled galeopericranial flap for reconstruction of the extradural and
      subcutaneous spaces of the frontal region, which were infected with methicillin
      resistant Staphylococcus aureus (MRSA) following unsuccessful coverage of the
      anterior cranial base with an anteriorly based pericranial flap. RESULTS: The
      patient healed uneventfully without infection. CONCLUSION: Because a bipedicled
      galeopericranial flap has abundant blood supply, it can be used to cover a wide
      segment of the anterior cranial base. This is the first report of the application
      of a bipedicled galeopericranial flap for wide reconstruction of the anterior
      cranial base.

PMID- 8860773
TI  - Cervical osteomyelitis after percutaneous transtracheal ventilation and
      tracheotomy.
AB  - BACKGROUND: Percutaneous transtracheal ventilation has proven useful in emergent
      airway management. METHODS: A report of a case is presented. Results. A 42-year
      old woman who developed laryngospasm required emergency airway intervention She
      developed massive subcutaneous emphysema and required emergent cricothyroidotomy
      which was immediately converted to a tracheotomy. Although she was quickly
      decanulated, she developed late cervical osteomyelitis which resolved with
      intravenous antibiotic therapy. CONCLUSIONS: Cervical osteomyelitis has not been
      previously reported as a complication of percutaneous transtracheal ventilation
      or tracheotomy Contamination of the deep neck spaces facilitated by pressure
      dissection of the fascial planes may have led to this complication.

PMID- 8860774
TI  - Vocal cord paralysis and benign thyroid disease.

PMID- 8860786
TI  - Purim syncope.

PMID- 8860787
TI  - Australian adolescent medicine physician appreciates journal of adolescent health
      issue on eating disorders.

PMID- 8860788
TI  - Coronary disease risk factor reduction and behavior modification in minority
      adolescents: the PATH program.
AB  - PURPOSE: To evaluate the impact of a unique school-based program of exercise,
      health education, and behavior modification on health knowledge, health
      behaviors, coronary risk factors, and cardiovascular fitness in minority
      adolescents. METHODS: A total of 346 students from an inner-city public high
      school participated in health promotion intervention or regular physical
      education volleyball classes. Subjects were African-American (47%), Asian
      American (9%), Hispanic (21%), white (3%), and other (19%). The health promotion
      curriculum consisted of 11 weeks of daily circuit training exercise and health
      lecture-discussions. RESULTS: The groups were similar in age, height, weight,
      ethnicity, and socioeconomic status. Following intervention both boys (P < .001)
      and girls (P < .006) significantly improved health knowledge test scores.
      Significant benefits for girls included improved dietary habits (P < .05),
      reduced cholesterol (P < .004), and higher estimated V(O2)max (P < .0001). There
      were no other significant changes in boys. CONCLUSIONS: The results suggest that
      a school-based health promotion program of exercise and health lecture-discussion
      is beneficial for multiethnic, inner-city adolescents, especially females.

PMID- 8860789
TI  - Searching for resilience among African-American youth exposed to community
      violence: theoretical issues.
AB  - PURPOSE: The exploration of resilience factors which may moderate the impact of
      violence exposure on African-American youth living in high-crime neighborhoods
      has received scant research attention. Yet, how these adolescents appraise and
      cope with exposures to violent events has implications for social adaptation and
      resilience. This article attempts to organize diverse literatures and cross
      disciplinary perspectives into an integrative framework for the study of
      resilience among African-American youth exposed to violence. METHODS: The search
      for protective factors requires critical examination of both the ethnocentric
      bias in traditional developmental frameworks and the decontextualization of
      sociocultural and environmental influences on adaptation. A paradigmatic
      refocusing is necessary, one which highlights the capacities for coping and
      adaptation resulting from the engagement of personal resources, family strengths,
      and community support systems. RESULTS: To facilitate this research, an appraisal
      and coping model of violence is presented. This model emphasizes the need to
      identify and assess the appraisal processes and coping strategies initiated by
      African-American families as they attempt to thrive amidst community violence.
      CONCLUSIONS: Protective factors, operative at different junctures and within
      different ecologies, may reduce the likelihood of maladaptation or promote social
      competence in African-American youth exposed to violence. This search for
      resilience must address the meaning of competence and mechanisms of familial and
      external support that are salient within the African-American community.

PMID- 8860790
TI  - The health and psychosocial status of HIV-seropositive youth in Minnesota.
AB  - OBJECTIVE: To describe the health outcomes and health care utilization of
      nonhemophiliac adolescents diagnosed with human immunodeficiency virus (HIV)
      infection. DESIGN: Cross-sectional survey. SUBJECTS: All state residents without
      hemophilia, 13-21 years of age at the time of HIV infection diagnosis, reported
      to the Department of Health through April 1992. SETTING: A state where HIV and
      acquired immune deficiency syndrome (AIDS) are reportable conditions. METHODS:
      Structured interviews. RESULTS: The survey response rate was 67%. Most subjects
      reported preexisting and current psychosocial problems. In 35% of cases, subjects
      did not recall giving consent for HIV antibody testing; and many reported that
      seropositive results were delivered inappropriately. Eighty-seven percent of
      subjects reported recent medical care, without statistically significant
      differences related to gender, race, or mode of transmission. Within 3.5 years
      (median) of the diagnosis of HIV infection, 55% of participants reported having
      physical limitations that were found only to be associated with duration of
      illness. CONCLUSIONS: The findings highlight the need for better understanding of
      the progression and comorbidities of HIV disease during adolescence, counseling
      and testing practices, and expanded access to supportive services.

PMID- 8860791
TI  - Risk for gonococcal and chlamydial cervicitis in adolescent females: incidence
      and recurrence in a prospective cohort study.
AB  - PURPOSE: This study attempted to determine the incidence and risk for gonococcal
      and chlamydial cervicitis among sexually active urban adolescent females.
      METHODS: The study design is a prospective cohort study. A cohort of 216 sexually
      active females were followed with repeat sexually transmitted diseases screening
      for 12-24 months. Subjects positive on any retest (FU) were compared with those
      who remained negative on all FU. Subjects were interviewed for history and
      screened for endocervical gonococcal and chlamydial infection. RESULTS: The
      number of visits per patient ranged from 2 to 9 (median, 3). The initial
      Chlamydia trachomatis and Neisseria gonorrhoeae rates were 23.2 and 11.6%,
      respectively. The cumulative FU positive rates were 20.8% for C. trachomatis and
      17.1% for N. gonorrhoeae. Although the initial gonococcal infection was a
      significant risk for a subsequent infection by C. trachomatis (p = .05) and N.
      gonorrhoeae (p = .001), the initial C. trachomatis status was not predictive of
      subsequent infections. The number of partners was not predictive of subsequent
      infections with either. In the entire study period, 86 patients had at least one
      episode of C. trachomatis and N. gonorrhoeae infection was confirmed in 52; 20
      patients had recurrent cervicitis. During the study, 101 episodes of C.
      trachomatis and 68 episodes of N. gonorrhoeae infections were identified. Those
      with recurrent cervicitis (9.3%) were responsible for 33% of all cervicitis
      episodes identified during the study. CONCLUSIONS: Adolescents in our study were
      at high risk for cervicitis, particularly as a result of C. trachomatis. Risk for
      subsequent C. trachomatis cervicitis was the same among initially positive and
      negative groups. Our data underscore the importance of repeat screening for
      sexually transmitted infections and treatment of contacts of adolescent females.

PMID- 8860792
TI  - Concurrent and prospective screening for problem drinking among college students.
AB  - PURPOSE: Previous studies suggest that combining the CAGE questionnaire with the
      Perceived Benefit of Drinking Scale (PBDS), information about an adolescent's use
      of tobacco, and best friend's drinking pattern is a useful composite screening
      measure for problem drinking. The present study was undertaken to evaluate this
      composite screening measure prospectively as a predictor of subsequent problem
      drinking among late adolescents across 3 years of college. METHODS: A random
      sample of 452 college freshmen entered a longitudinal study of alcohol use at the
      beginning of their freshman year. A total of 184 (58%) completed follow-up
      measures of alcohol use 32 months later. Outcome measures included the quantity
      and frequency of alcohol use and a composite measure of specific alcohol-related
      problems. RESULTS: CAGE scores, PBDS scores, tobacco use, and best friend's
      drinking patterns as reported at college entry together explained 33% of the
      variance in the quantity/frequency measure and 37% of the variance in the alcohol
      related problems measure from the end of the junior year. These same variables as
      reported at the end of the junior year explained 50% of the variance in the
      quantity/frequency measure and 61% of the variance in the alcohol-related
      problems measure. The composite screening measure as reported at college entry
      had a sensitivity of 73%, specificity of 70%, positive predictive value (PPV) of
      63%, and negative predictive value (NPV) of 78% for students at high risk for
      problem drinking at the end of the junior year. A similar concurrent composite
      screening measure consisting of the same variables reported at the end of the
      junior year had a sensitivity of 88%, specificity of 56%, PPV of 60%, and NPV of
      83% for high-risk drinkers. A total of 70-73% of students could be correctly
      categorized by each composite screening measure. These composite screening tests
      had significantly better test characteristics than the CAGE or PBDS alone.
      CONCLUSIONS: College students' responses to the CAGE, PBDS, tobacco use, and
      their friends' drinking remain consistent over 3 years and correlate with
      concurrent and future risk for problem drinking. These variables explain
      significant variance in drinking and alcohol-related problems and may constitute
      a useful screening measure for current and future problem drinking.

PMID- 8860793
TI  - Premenarcheal expectations and postmenarcheal experiences of positive and
      negative menstrual related changes.
AB  - PURPOSE: Longitudinal examination of early adolescent girls' premenarcheal
      expectations and postmenarcheal experiences of positive and negative menstrual
      related changes. METHOD: Ratings of 14 positive and negative changes were made by
      80 girls on three occasions: (1) in grade 6 when girls were premenarcheal, (2) at
      the test occasion within six months after each girls' own menarche, and (3) in
      grade 9 when girls were postmenarcheal. Premenarcheal girls rated expectations of
      changes, and postmenarcheal girls rated experiences of changes, for both
      premenstrual and menstrual phases. Girls also rated preparation for, and
      emotional response to, menarche and mothers' helpfulness on the first two
      occasions. RESULTS: Ratings for positive and negative changes were at similar
      levels premenarcheally and decreased at menarche; once menstruation became
      established, ratings of negative changes increased while those of positive
      changes decreased. Ratings for negative changes were higher in the menstrual
      phase, while ratings for positive changes were higher in the premenstrual phase.
      Premenarcheal expectations of changes contributed to the prediction of menarcheal
      experiences of changes. Premenarcheal expectations and menarcheal experiences,
      along with anticipated emotional response to menarche, contributed to the
      prediction of longer-term experience of negative changes; menarcheal experiences,
      along with preparation for and emotional response to menarche, contributed to the
      prediction of longer-term experience of positive changes. CONCLUSIONS: Both
      expectations about, and initial experiences of, menstrual cycle-related changes
      were associated with longer-term menstrual experiences. The different outcomes
      for positive and negative changes have implications for menstrual socialization,
      and provide the basis for some optimism about facilitating a more complex and
      multidimensional understanding of menstruation.

PMID- 8860794
TI  - Dietary intakes of adolescent females consuming vegetarian, semi-vegetarian, and
      omnivorous diets.
AB  - PURPOSE: To determine the energy and nutrient intakes of some omnivorous and
      vegetarian female adolescents to compare their risk for nutrient inadequacies.
      METHODS: A convenience sample of 78 lacto-ovo-vegetarians (LOV), 15 semi
      vegetarians (SV), and 29 omnivorous (OM) females aged 14-19 years completed three
      day weighed records from which mean intakes and major food sources of energy,
      nutrients, and dietary fiber (as nonstarch polysaccharides (NSP)) were
      calculated. RESULTS: Mean daily intakes for energy and most nutrients were
      comparable for the three groups although LOV had higher intakes (p < 0.01) of
      NSP, copper, and manganese. Lacto-ovo-vegetarians consumed (g/d) less dairy
      products, flesh foods, and sweets but more legumes, nuts, and vegetables. Major
      food sources were cereal products for energy, most nutrients, NSP, dairy products
      for calcium, and fruits and vegetables for vitamin C. More LOV and SV had energy
      intakes less than two-thirds of Canadian recommendations, and higher probability
      estimates of inadequacy for protein, calcium, iron, zinc, and riboflavin than OM.
      Fewer LOV (35%) than SV (53%) and OM (41%) had diets with less than 30% energy
      from fat. CONCLUSIONS: LOV and SV were more at risk for nutrient inadequacies
      than OM, although about 33% of OM were also at risk for inadequate intakes of
      iron and zinc.

PMID- 8860795
TI  - Follow-up study of adolescent girls with a history of premature pubarche.
AB  - A total of 37 girls with a history of benign premature pubarche were followed
      into puberty; a disproportionate number of girls experienced early menarche.
      Twenty-five had some degree of acne, 14 had hirsutism, and 5 had acanthosis
      nigricans. Body mass index (BMI) at initial presentation correlated with
      postpubertal BMI and was weakly correlated with postpubertal hirsutism.

PMID- 8860796
TI  - Adolescent inpatient units: a position statement of the Society for Adolescent
      Medicine.

PMID- 8860798
TI  - Is there muscle pathology in fibromyalgia syndrome?
AB  - A number of studies have reported abnormalities in the muscles of fibromyalgia
      patients. The early studies, some of which indicated morphologic abnormalities,
      had major problems with patient selection and lacked adequate control groups.
      More recent studies of morphology have shown only nonspecific or mild changes,
      perhaps consistent with subtle metabolic abnormalities, especially at tender
      point sites. Studies of muscle metabolism, however, particularly the more
      rigorous studies using MR spectroscopy, have failed to confirm abnormalities in
      muscle metabolism, both at tender and nontender point locations. The
      abnormalities detected in earlier studies appear to have been confounded by
      subtle metabolic changes resulting from muscle deconditioning. Studies of muscle
      blood flow also demonstrate abnormalities that can be explained by deconditioning
      alone. Studies of muscle strength that show differences between patients and
      controls can be explained by lack of voluntary effort. A popular theory of the
      genesis of pain in fibromyalgia syndrome was that excessive muscle tension led to
      increased excitability of nociceptors in muscle leading to muscle hypertension
      and chronic pain. Furthermore, defective sympathetic control was proposed to
      result in disturbed microcirculation and nociceptor excitation. In aggregate,
      however, studies using EMG techniques show no evidence of excessive muscle
      tension or defective sympathetic nervous function. Therefore, although muscular
      pain has been a central feature of fibromyalgia syndrome, controlled studies of
      muscle fail to support a convincing role for muscle in the pathophysiology of the
      condition. Muscle tenderness in fibromyalgia cannot be explained on the basis of
      primary muscle abnormalities, either structural or functional. Future
      pathophysiologic studies in fibromyalgia should focus on central mechanisms.

PMID- 8860799
TI  - Evidence that abnormalities of central neurohormonal systems are key to
      understanding fibromyalgia and chronic fatigue syndrome.
AB  - Fibromyalgia (FM) and chronic fatigue syndrome (CFS) fall into the spectrum of
      what might be termed stress-associated syndromes by virtue of frequent onset
      after acute or chronic stressors and apparent exacerbation of symptoms during
      periods of physical or emotional stress. These illnesses also share perturbation
      of the hypothalamic-pituitary-adrenal axis and sympathetic stress response
      systems. In this article, the authors discuss the specific neurohormonal
      abnormalities found in FM and CFS and potential mechanisms by which dysfunction
      of neurohormonal stress-response systems could contribute to vulnerability to
      stress-associated syndromes and to the symptoms of FM and CFS.

PMID- 8860800
TI  - The relationship between fibromyalgia and major depressive disorder.
AB  - Looking at the results of the seven types of studies discussed previously, it
      appears that there is strong evidence for an association between fibromyalgia and
      major depressive disorder on the basis of (1) overlapping symptomatology, (2)
      similar pattern of comorbid disorders, and (3) high rates of major depressive
      disorder among relatives of patients with fibromyalgia. There is additional
      support for an association on the basis of responses to psychological tests and
      rating scales and the high lifetime rates of mood disorders in fibromyalgia. Two
      lines of evidence, (1) response to antidepressant medications and (2) response to
      biologic tests, offer little evidence either for or against an association. On
      balance, then the weight of the evidence favors an association between
      fibromyalgia and major depressive disorder. We therefore turn to an analysis of
      the nature of the association.

PMID- 8860801
TI  - Trigger points and tender points: one and the same? Does injection treatment
      help?
AB  - Trigger points are defined as areas of muscle that are painful to palpation and
      are characterized by the presence of taut bands and the generation of a referral
      pattern of pain. Tender points are areas of tenderness occurring in muscle,
      muscle-tendon junction, bursa, or fat pad. When tender points occur in a
      widespread manner, they are usually considered characteristic of fibromyalgia.
      Trigger points, which typically occur in a more restricted regional pattern, are
      indicative of myofascial pain syndrome. In some patients the two phenomena may
      coexists, and overlap syndromes can occur. Although experienced examiners can
      generally identify the same tender points, interrater reliability of trigger
      points has been low in most studies. There is continued controversy regarding the
      defining characteristics and homogeneity of myofascial pain because of the
      variability of the examination findings. In appropriately selected patients, it
      appears that myofascial trigger point injections can be helpful in decreasing
      pain and improving range of motion in conjunction with a comprehensive exercise
      and rehabilitation program.

PMID- 8860802
TI  - A cost-effective approach to the diagnosis and treatment of fibromyalgia.
AB  - The diagnosis of teh myalgic patient can prove to be challenging for even the
      most experienced of clinicians. The differential diagnosis includes many diseases
      that often present with weakness as well as pain. The diagnosis of fibromyalgia
      may now be made using the positive features of the patient's illness and
      classified according to well-defined criteria. The process is facilitated by the
      demonstration of FTPs that are quite specific for the condition. The elicitation
      of tenderness over these points is highly reliable and valid owing to high
      intrarater and interrater agreements observed in multiple studies. An algorithmic
      approach to differential diagnosis is presented. In addition, a stepwise approach
      to treatment based on published studies and geared to functional outcome measures
      in put forward in an attempt to encourage a cost-effective approach to care of
      these difficult patients.

PMID- 8860803
TI  - Multidisciplinary group programs to treat fibromyalgia patients.
AB  - There are three realities that need to be understood by both clinicians and
      patients: (1) fibromyalgia is a complex chronic pain condition and current
      treatment is palliative rather than curative; (2) the major aim of treatment is
      to improve function, not abolish pain; and (3) a cycle of chronic pain, stress,
      and psychological arousal often generates a set of secondary symptoms. These
      secondary symptoms provide a positive feedback loop that is amenable to
      modification by cognitive-behavioral techniques. Multidisciplinary group
      treatment programs are especially suited to such techniques; their aim should be
      to maximize subsequent clinician-patient interactions. Thus, a current concept of
      optimal management is a blend of multidisciplinary group therapy and
      individualized clinician-based treatment.

PMID- 8860804
TI  - Fibromyalgia and work disability: Is Fibromyalgia a disabling disorder?
AB  - Fibromyalgia appears to be an increasingly important source of disability claims
      and payments. Twenty-five percent of patients seen in rheumatology clinics have
      received disability payments. Yet fibromyalgia is a clinical rather than a legal
      construct, and there remain very important limitations regarding the reliability
      and validity of diagnosis and severity assessments outside of the clinic and in
      the medicolegal setting. Even so, preparation of disability assessments that
      cover key requirements can provide substantial assistance to disability
      adjudicators.

PMID- 8860805
TI  - What is the future of fibromyalgia?
AB  - This article discusses the future of fibromyalgia, including the current state of
      the art and potential future pathophysiologic studies. Suggestions are provided
      in regard to future therapeutic trials, longitudinal and outcome studies, and the
      role of the rheumatology community in this common disorder.

PMID- 8860831
TI  - Public oversight is necessary if human gene therapy is to progress.

PMID- 8860832
TI  - Retrovirus-mediated suicide gene transduction in the vitreous cavity of the eye:
      feasibility in prevention of proliferative  vitreoretinopathy.
AB  - In proliferative vitreoretinopathy (PVR), retinal pigment epithelial cells,
      fibroblasts, or other proliferating cells form contractile membranes in the
      vitreous cavity of the eye, resulting in traction retinal detachment. Retroviral
      vector-mediated transfer is a suitable method to transduce the herpes simplex
      virus thymidine kinase (HSV-tk) gene into proliferating cells in PVR, allowing
      for the selective killing of these cells. To determine the potential of gene
      transduction in the environment of the vitreous cavity, we evaluated the effect
      of vitreous humor on retroviral vector-mediated gene transduction of rabbit
      dermal fibroblasts in vitro and studied in vivo transduction in rabbit
      experimental PVR with retroviral vector G1BgSvNa. In addition, we studied the
      bystander effect in vitro and in vivo in a rabbit model of PVR, with low
      percentages of HSV-tk-positive cells. Finally, we evaluated the efficacy of
      intravitreal administration of HSV-tk retroviral vector G1TkSvNa followed by
      ganciclovir (GCV) in the prevention of experimental PVR. Vitreous humor reduced
      gene transfer efficiency in vitro in a dose-dependent manner. LacZ expression was
      found in cells of preretinal or intravitreal membranes of animals of both in vivo
      and in vitro transduction groups; however, in vivo transduction resulted in a
      decreased number of transduced cells, with a relative transduction efficiency of
      approximately 2%. Transduction of HSV-tk was associated with a powerful bystander
      effect both in vitro and in vivo with significant effects even when HSV-tk
      positive cells represented only 1% of the population. In vivo transduction with
      G1TkSvNa followed by GCV significantly inhibited the development of PVR (p <
      0.05). These results suggest that retroviral vector-mediated transfer of HSV-tk
      into the proliferating cells in PVR may be feasible and may provide a novel
      therapeutic strategy for this disease.

PMID- 8860833
TI  - TAXI/UAS: A molecular switch to control expression of genes in vivo.
AB  - Numerous therapies and biological questions could be addressed in mammals by the
      application of a molecular switch that would allow physicians and/or
      investigators to turn individual genes on or off during the lifetime of the
      organism. We have constructed such a switch, composed of three elements: (i) an
      inducible promoter that is normally absent from mammalian genomes; (ii) a
      receptor that, when it is bound to an inducer drug, specifically activates
      transcription from the inducible promoter; and (iii) inducer drugs, such as
      RU486, whose pharmacological properties in humans and several mammalian species
      including mouse have been well studied. The molecular switch is functional in
      transiently and stably transfected cells. Importantly, both the total output and
      the induction levels of the reporter gene can be finely tuned, with induction
      levels of over 100-fold being readily attained. Finally, we demonstrate that the
      molecular switch can be used to regulate a mouse transgene using a gene therapy
      paradigm. The specificity of the system suggests that it should be useful in the
      analysis of gene function in transgenic animals and in the design of strategies
      for human gene therapy.

PMID- 8860834
TI  - Correction of ornithine transcarbamylase deficiency in adult spf(ash) mice and in
      OTC-deficient human hepatocytes with recombinant adenoviruses bearing the CAG
      promoter.
AB  - Ornithine transcarbamylase (OTC) deficiency, the most common and severe inborn
      error of the urea cycle in humans, remains without adequate treatment, and
      mortality rates are high. Adenoviral vectors provide an efficient system for gene
      delivery, but there are problems, including toxicity. Efficient promoters that
      reduce the amount of vector required for treatment need to be developed. We
      constructed two recombinant adenoviral vectors, AdexCAGhOTC and AdexSR alpha
      hOTC, which harbor the human OTC gene under transcriptional control of CAG (a
      modified chicken beta-actin promoter with CMV-IE enhancer) and SR alpha (the SV40
      early promoter with the R segment and part of the US segment of the HTLV-1 LTR),
      respectively. Each was tested in adult spf(ash) mice, an animal model of human
      OTC deficiency, and in primary human hepatocytes with OTC deficiency. Spf(ash)
      mice have a pronounced orotic aciduria as seen in humans. A complete recovery of
      hepatic OTC activity with minimal tissue damage was observed in these animals
      following the intravenous administration of AdexCAGhOTC alone. Western blot
      analysis confirmed hepatic OTC expression and normalization of orotic aciduria
      was evident for 60 days. Enzyme activities of primary human hepatocytes infected
      with AdexCAGhOTC were 10-40 times higher than those with AdexSR alpha hOTC. Thus,
      the adenoviral vector with an efficient promoter such as CAG, can be given
      further consideration for possible gene therapy in humans with OTC deficiency.

PMID- 8860835
TI  - Retrovirus-mediated gene transfer of rat glutathione S-transferase Yc confers in
      vitro resistance to alkylating agents in human leukemia cells and in clonogenic
      mouse hematopoietic progenitor cells.
AB  - Recently, we have reported that N2Yc, a Moloney-based retrovirus vector
      expressing the Yc isoform of rat glutathione S-transferase (GST-Yc), conferred
      resistance to alkylating agents in mouse NIH-3T3 fibroblasts. In this report, we
      address the feasibility of using rat GST-Yc somatic gene transfer to confer
      chemoprotection to the hematopoietic system. Human chronic myelogenous leukemia K
      562 cells were efficiently transduced with the N2Yc retrovirus vector and showed
      a significant increase in the 50% inhibitory concentration of chlorambucil (3.2-
      to 3.3-fold), mechlorethamine (4.7- to 5.3-fold), and melphalan (2.1- to 2.2
      fold). In addition, primary murine clonogenic hematopoietic progenitor cells
      transduced with the N2Yc vector were significantly more resistant to alkylating
      agents in vitro than cells transduced with the antisense N2revYc vector. The
      survival of Yc-transduced hematopoietic colonies at 400 nM mechlorethamine and 4
      mu M chlorambucil was 39.4% and 42.6%, respectively, compared to 27.2% and 30.4%
      for N2revYc-transduced cells. Future experiments will determine the level of
      chemoprotection achievable in vivo, following transplantation of N2Yc-transduced
      hematopoietic cells in mice.

PMID- 8860836
TI  - Effects of gamma irradiation on the transduction of dividing and nondividing
      cells in brain and muscle of rats by adeno-associated virus vectors.
AB  - Vectors based on adeno-associated virus (AAV) are under investigation for use in
      gene therapy applications. Critical aspects of AAV vector biology remain
      undefined, in particular the intracellular events and activities mediating
      transduction and determining host cell permissiveness for transduction. Using
      cultured primary human fibroblasts, we previously showed that AAV vectors
      preferentially, but not exclusively, transduce cells in the S phase of the cell
      cycle, and that transduction can be markedly enhanced by pretreatment of target
      cells with physical and chemical agents that perturb DNA metabolism. In this
      study, we tested whether similar improvements in AAV vector performance might be
      achievable in vivo. The adult rat brain and overlying scalp muscle were selected
      for vector inoculation because of the presence of well-defined populations of
      dividing, quiescent, and post-mitotic cells, and gamma irradiation was chosen as
      a reproducible means of inducing DNA repair in these cells. We find that gamma
      irradiation markedly enhances the transduction of dividing cell populations in
      the pia-arachnoid and choroid epithelium within the central nervous system, and
      of mature nondividing muscle cells in the scalp, whereas gamma irradiation did
      not increase the basal transduction level of post-mitotic neurons in the
      hippocampus. These data confirm that replicative cellular DNA synthesis is not
      required for transduction by AAV vectors and show that the mitotic state of
      target cells is not necessarily predictive of responsiveness to transduction
      enhancing treatments. Most importantly, these data demonstrate that target cells
      can be manipulated in vivo to render them more permissive for AAV vector
      transduction.

PMID- 8860837
TI  - Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated
      xenogenic cell line engineered to secrete hCNTF.
AB  - The gene therapy approach presented in this protocol employs a polymer
      encapsulated, xenogenic, transfected cell line to release human ciliary
      neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis
      (ALS). A tethered device, containing around 10(6) genetically modified cells
      surrounded by a semipermeable membrane, is implanted intrathecally; it provides
      for slow continuous release of hCNTF at a rate of 0.25 to 1.0 micrograms/24
      hours. The semipermeable membrane prevents immunologic rejection of the cells and
      interposes a physical, virally impermeable barrier between cells and host.
      Moreover, the device and the cells it contains may be retrieved in the event of
      side effects. A vector containing the human CNTF gene was transfected into a line
      of baby hamster kidney cells (BHK) with calcium phosphate using a dihydrofolate
      reductase-based selection vector with a SV40 promoter and contains a HSV-tk
      killer gene. hCNTF is a potent neurotrophic factor which may have utility for the
      treatment of ALS. Systemic delivery of hCNTF in humans has been frustrated by
      peripheral side effects, the molecule's short half life, and its inability to
      cross the blood-brain barrier. The gene therapy approach described in this
      protocol is expected to mitigate such difficulties by local intrathecal delivery
      of a known quantity of continuously-synthesized hCNTF from a retrievable implant.

PMID- 8860838
TI  - Modification of tumor suppressor gene expression in non-small cell lung cancer
      (NSCLC) with a retroviral vector expressing wildtype (normal) p53.

PMID- 8860840
TI  - Multiplane transesophageal echocardiography: examination technique, anatomic
      correlations, and image orientation.
AB  - Multiplane (TEE) transducer imaging is the most highly evolved TEE technology at
      present. New clinical applications of this technology will be realized as
      echocardiographers gain experience with it. Current limitations of TEE are likely
      to be surmounted as its use increases, and continuous improvements and
      miniaturization of the technology also will improve its usefulness in practice.

PMID- 8860841
TI  - Critical appraisal of transesophageal echocardiography: limitations and pitfalls.
AB  - As with any imaging technology, there are limitations and pitfalls to TEE. The
      limitations and pitfalls of TEE can be minimized best by experience. Initial
      training should not be circumvented, and maintenance of competency should be
      monitored strictly. Physicians with less than level II echocardiography training
      should work in close collaboration with an active echocardiography laboratory and
      have an appropriate review of current examinations. Both individual and
      laboratory standards for maintenance of competency should be established. Because
      of the new presentation of cardiac and extracardiac anatomy, unfamiliar but
      normal anatomy initially may be confused as abnormal. Additionally, certain
      structures are viewed in a manner that may mimic pathologic conditions. Because
      of the superior resolution offered by TEE, phenomena such as spontaneous contrast
      and ghosting are observed much more commonly than they are with transthoracic
      imaging. Highly detailed anatomic structures, such as atrial muscle bundles,
      sutures, and adipose tissue, are to be recognized and differentiated from
      thrombi, vegetation, and masses. Although TEE has been a dramatic step forward in
      diagnostic imaging, there is a potential for serious misinterpretation. This
      article discusses most of these potential problems; however, there always will be
      unique situations in which the findings must be addressed consistently and
      differentiated as normal, artifact, new observation, or misinterpretation.

PMID- 8860842
TI  - Assessment of left ventricular function and hemodynamics with transesophageal
      echocardiography.
AB  - Transesophageal echocardiography (TEE) plays an important role in the evaluation
      of left ventricular function and hemodynamics in the critical care setting. The
      technique provides immediate data regarding regional myocardial ischemia, global
      ventricular function, volume, and the presence of cardiac tamponade. This article
      outlines the role of TEE in the evaluation of left ventricular function in the
      intensive care unit and presents practical information for the use of TEE in
      evaluating systolic function, diastolic function, and cardiac tamponade.

PMID- 8860843
TI  - Transesophageal echocardiographic assessment of embolic sources: intracardiac and
      extracardiac masses and aortic degenerative disease.
AB  - The increased sensitivity of transesophageal echocardiography (TEE) makes it
      complementary and, in many cases, superior to transthoracic echocardiography in
      the detection of various sources of embolism. These sources include intracardiac
      thrombus, tumors, spontaneous echocardiographic contrast, and others. TEE is also
      helpful as an adjunctive test for the diagnosis of pulmonary embolisms.

PMID- 8860844
TI  - Intracardiac shunts.
AB  - Unsuspected intracardiac shunts can be a cause of acute deterioration in
      critically ill patients. Shunts can be acquired or congenital conditions that
      become symptomatic only with changed physiologic conditions. Transesophageal
      echocardiography is an excellent tool for the diagnosis of intracardiac shunts.

PMID- 8860845
TI  - Transesophageal echocardiographic evaluation of native valvular disease and
      repair.
AB  - Surgery for valvular heart disease corrects systolic or diastolic dysfunction of
      the mitral, aortic, or tricuspid valves. The intraoperative echocardiographic
      assessment of the native heart valve is aimed at defining the pathology of valve
      disease, determining the mechanism of valve dysfunction, and quantitating the
      degree (grade) of valvular stenosis or insufficiency.

PMID- 8860846
TI  - Echocardiography and Doppler assessment of prosthetic heart valves with
      transesophageal echocardiography.
AB  - This article examines the use of transesophageal echocardiography (TEE) in the
      assessment of prosthetic heart valves. A summary of the commonly used artificial
      valves and their physiologic regurgitant flow patterns, as identified by color
      Doppler imaging, is presented. The hemodynamic evaluation of prosthetic valve
      stenosis using Doppler techniques is reviewed, and the diagnostic utility of TEE
      in identifying the complications of cardiac prostheses is discussed.

PMID- 8860847
TI  - Assessment of endocarditis and associated complications with transesophageal
      echocardiography.
AB  - TEE offers many benefits in the evaluation of patients with IE. It provides
      increased sensitivity as compared to TTE in the detection of this disease, and is
      better able to identify and delineate many of the associated complications and
      hemodynamic aberrancies. TEE also has helped expand our knowledge of the
      pathophysiology and natural history of IE. Continued advances in the technology
      of TEE instrumentation undoubtedly will lead to further improvements in our
      ability to assess and to treat patients stricken with this serious infection.
      Nevertheless, IE continues to exact a significant toll on its victims, and our
      efforts to diagnose, to treat, and to prevent it must not weaken.

PMID- 8860848
TI  - Stress echocardiography, contrast echocardiography, and tissue characterization:
      applications for the future.
AB  - During the last three decades the application of ultrasonography has expanded
      rapidly. The information available to the clinician from ultrasound imaging today
      is vastly more significant than it was in the early years of the development of
      this technology. In addition to automatic information, there is an increasing
      potential to provide functional, dynamic perfusion and even cellular information
      about the heart. This article attempts to summarize briefly the advances in these
      areas.

PMID- 8860849
TI  - Intravascular and intracardiac ultrasound: a tool of the future.
AB  - Intravascular ultrasonography has the capability to visualize the vessel wall and
      perivascular structures, to identify the spatial distribution and composition of
      atherosclerotic plaque, and to measure accurately vessel and wall dimensions.
      This article discusses relevant principles of instrumentation, issues pertaining
      to the validation and interpretation of intravascular ultrasound images, and the
      current and potential applications of intravascular (and intracardiac) imaging.
      Emphasis is placed on uses that are likely to be of interest to the critical care
      physician.

PMID- 8860850
TI  - Automatic border detection and three-dimensional reconstruction with
      echocardiography.
AB  - This article reviews two important innovations in echocardiography resulting from
      the recent advances in the capabilities of microprocessors. The first, automatic
      endocardial border detection, has been implemented on computers contained
      entirely within echocardiograph machines and is gaining wide clinical use. The
      second, three-dimensional imaging, is currently under intense investigation and
      shows great promise for clinical application. It requires, however, further
      development of the specialized transducer apparatus necessary for image
      acquisition and the sophisticated computer-processing capability necessary for
      image reconstruction and display.

PMID- 8860851
TI  - Commentary. Aging.

PMID- 8860861
TI  - Topical vitamin C in aging.

PMID- 8860881
TI  - Donor insemination, the impact on family and child development.
AB  - The practice of donor insemination (DI) has undergone major changes in the past
      20 years. Attention was paid to the long-term psychological effects, the pleas
      for openness became stronger over the years and the use of anonymous donors
      became subject to public debate in several countries. The present article reviews
      what empirical research there is into DI families and their children. Over the
      years follow up studies have appeared sporadically and in spite of the varying
      quality of the research methods, preliminary findings have emerged. Research into
      the confidentiality issue in DI couples revealed that 47-92% of the DI parents
      intended to keep the donor origin secret from their children. DI couples just
      starting treatment more often intended to tell their children the DI origin than
      those who already had children. It is, however, too early to tell whether the
      public pleas for more openness did affect attitudes of the DI patients
      themselves. Research into the psychological well-being of DI parents and children
      failed to reveal major psychological problems. DI parents appeared to be well
      adjusted and to have stable marital relationships. DI children did not show
      significantly more emotional disturbances than controls. The quality of the
      parent-child relationship was better in the DI group than in the controls of
      naturally conceived parents.

PMID- 8860882
TI  - The effect of sexual experience on the attitudes of medical students to learning
      gynecological examinations.
AB  - The influence of sexual experience and gender on the attitudes of medical
      students to the methods of teaching the gynecological examination was studied.
      Data were obtained by questionnaire from students who had completed their
      obstetric/gynecological and family medicine clinical terms. Two hundred and
      eighty-six students agreed to participate. Ninety of the male students (53%) and
      63 (54%) of the female students had experienced sexual intercourse. Students,
      male and female, who were sexually experienced felt they were more able to
      conduct a gynecological examination with sensitivity, put the woman at ease and
      to explain to the women what was being done and why. Male students who had not
      experienced sexual intercourse felt less able to perform a speculum examination,
      to do a Papanicolaou smear or be able to detect an abnormality. There were no
      gender differences between the preferred methods of learning to conduct a
      gynecological examination but non-sexually experienced students ranked higher the
      examination of a woman under anesthesia. The suggestion of student volunteers was
      more acceptable to sexually experienced women and non-sexually experienced male
      students. Students varied in their response to being volunteers for students
      learning to conduct vaginal or rectal (if male) examinations. If only the same
      sex were present 31% of non-sexually experienced male students would possibly
      volunteer for rectal examination and 39% of sexually experienced female students
      for vaginal examination. Sexual experience influences students' choice of methods
      for learning to conduct a gynecological examination.

PMID- 8860883
TI  - Can one induce premenstrual symptomatology in women with prior hysterectomy and
      bilateral oophorectomy?
AB  - Nine women who had undergone hysterectomy and oophorectomy and who previously
      suffered from severe premenstrual syndrome (PMS) were given estrogen and
      progesterone in a naturalistic single-blind paradigm. The 13-item Beck Depression
      Inventory, Spielberger State Anxiety Inventory, Menstrual Distress Questionnaire
      and the Daily Ratings Form of the Premenstrual Assessment Form were all given
      daily. Estradiol and progesterone concentrations were estimated. When results
      from all subjects were considered together, these measures were not correlated
      with hormonal status. However, individual subjects showed correlations between
      some symptom scores and serum progesterone concentrations. We conclude that women
      diagnosed as having PMS do not respond in a uniform fashion to ovarian hormones.
      Further quantitative studies are needed to relate these individual differences to
      the syndrome of PMS.

PMID- 8860884
TI  - Effect of progesterone and its 5 alpha and 5 beta metabolites on symptoms of
      premenstrual syndrome according to route of administration.
AB  - Orally administered progesterone may have advantages over other routes of
      administration in the treatment of premenstrual syndrome (PMS) because of
      substantially higher levels of the anxiolytic metabolites 5 alpha and 5 beta
      pregnanolone. The only previous placebo-controlled trial which used oral
      progesterone reported beneficial effects in the treatment of PMS. The present
      study, a double-blind crossover trial, compared the administration of 300 mg
      daily oral progesterone with 200 mg daily vaginal progesterone and matched
      placebos for 10 days premenstrually. Although there was a significant treatment
      effect on symptoms, no difference between active treatments and placebo was
      found. The trial was terminated with 25 women completing treatment as it was
      evident that no clinically significant effect of either form of progesterone was
      likely to be detected even with twice the sample size. Serum levels of
      progesterone and metabolites showed that oral administration resulted in
      supraphysiological levels of 5 alpha and 5 beta metabolites and there was a
      negative correlation between 5 alpha pregnanolone levels and anxiety. However,
      this did not translate to overall reduction in premenstrual distress or anxiety
      beyond that achieved by placebo, as measured by validated questionnaires.

PMID- 8860885
TI  - Chronic pelvic pain and gynecological symptoms in women with irritable bowel
      syndrome.
AB  - Chronic pelvic pain and irritable bowel syndrome are common disorders, yet very
      little is known about their comorbidity. As part of an epidemiological study of
      patients with irritable bowel syndrome or irritable bowel disease we inquired
      about a history of chronic pelvic pain and related gynecological problems, and
      hypothesized that distress associated with either of these conditions was
      additive in women with both syndromes. A medically trained interviewer evaluated
      a sequential sample of 60 women with irritable bowel syndrome and 26 women with
      inflammatory bowel disease in an urban gastroenterology clinic using the National
      Institute of Mental Health Diagnostic Interview Schedule, the Briere Child
      Maltreatment Interview (emotional, physical and sexual abuse), and a structured
      interview to elicit a lifetime history of chronic pelvic pain that was distinct
      from the history of bowel distress. Chronic pelvic pain was reported in 21
      (35.0%) of the irritable bowel syndrome patients vs. 4 (13.8%) of the
      inflammatory bowel disease group (p < 0.05). Compared to women with irritable
      bowel syndrome alone, those with both irritable bowel syndrome and chronic pelvic
      pain were significantly more likely to have a lifetime history of dysthymic
      disorder, current and lifetime panic disorder, somatization disorder, childhood
      sexual abuse and hysterectomy. Logistic regression showed that mean number of
      somatization symptoms was the best predictor of a history of both irritable bowel
      syndrome and chronic pelvic pain compared either to inflammatory bowel disease or
      irritable bowel syndrome alone. Many women with irritable bowel syndrome may have
      a history of chronic pelvic pain as well. The high rates of psychopathology
      associated with irritable bowel syndrome and chronic pelvic pain independently
      are even higher in women with both syndromes, and women who present with either
      irritable bowel syndrome or chronic pelvic pain should probably be evaluated for
      both disorders.

PMID- 8860886
TI  - What men say about pregnancy, birth and parenthood.
AB  - Fathers' experiences during their transition to parenthood have been less well
      documented than those of mothers. This study explored the perceptions of three
      groups of fathers: fathers were asked to complete a questionnaire covering their
      experiences during their partner's pregnancy, during antenatal preparation
      programs or during birth. Fathers in all three groups were asked to respond to a
      follow-up questionnaire about parenthood. Their views are reported.

PMID- 8860887
TI  - Psychological aspects of nipple pain in lactating women.
AB  - The aim of the study was to assess the psychological impact of nipple pain in
      lactating women. Forty-eight lactating women with nipple pain completed mood
      scales at their first visit and following resolution of their pain, and 65
      lactating women without nipple pain completed one set of mood scales. At the
      first visit, the mean score on the Edinburgh Postnatal Depression Scale (EPDS) in
      the nipple pain group was 12.4 and the control group was 7.6 (p < 0.0001).
      Eighteen women (38%) scored above the threshold for depression (> 12), compared
      to nine in the control group (14%): p < 0.01. Following pain resolution, the mean
      score on the EPDS decreased to 7.3 (p < 0.001); and six women (16%) scored 13 or
      over on the EPDS, significantly less than initially (p < 0.05). Similarly, on the
      Profile of Mood States (POMS), the nipple pain group scored significantly higher
      than control group on all mood factors (Tension, Depression, Fatigue, Confusion,
      Vigor [lower]), except Anger which did not reach a level of significance. After
      pain resolution, POMS scores returned to similar levels as the control group. In
      conclusion, both the EPDS and POMS indicated women with nipple pain were
      experiencing high levels of emotional distress. However, once the pain had
      resolved their distress also resolved.

PMID- 8860888
TI  - Family planning in Vietnam--women's experiences and dilemma: a community study
      from the Red River Delta.
AB  - In traditional Vietnamese culture the expectations on women were to get at least
      one son, who could carry on the lineage. In the 1980s, a two-child population
      policy was introduced and family planning campaigns intensified. The aim of this
      study was to explore women's experience of family planning in relation to the
      potentially conflicting demands on their fertility. Data on reproductive
      histories and contraceptive use were collected in a random sample survey among
      206 women of reproductive age in Thai Binh province, northern Vietnam.
      Qualitative data were obtained in interviews with a selected group of women. Over
      half of the women used modern contraception, mainly the intrauterine device
      (IUD). The perceived side-effects of the IUD were higher than those reported by
      local health workers or from clinical studies of the same IUD. Women's problems
      in fertility regulation are discussed in the broader context of a society in
      transition. The importance of male progeny was still strong. Many families with
      'only' daughters had a third child, contrary to the two-child policy. It is
      suggested that conflicting demands on women's fertility are reflected in the high
      rates of IUD-complaint and psychosomatic side-effects. Improved services and
      wider contraceptive choice are needed, as well as research on the interaction
      between population policies, sociocultural change and women's health.

PMID- 8860905
TI  - Evaluation of NCRP Report No. 49 assumptions on workloads and use factors in
      diagnostic radiology facilities.
AB  - A survey of modern medical institutions has been performed to measure the
      workload and primary beam use factors used in diagnostic x-ray installations in
      comparison to those suggested in Report 49 of the NCRP. Seven types of radiology
      installations were investigated, namely general radiographic rooms, general
      fluoroscopic and radiographic rooms (fluoroscopic and radiographic tubes surveyed
      separately), chest radiographic rooms, mammographic suites, and cardiac and
      peripheral angiographic suites. The radiologic technique (kVp and mAs) for each
      exposure performed on a total of 2396 patients was recorded either manually or by
      a commercially-available invasive electronic sensing system. Additionally, the
      direction of the primary beam during the exposure was recorded. The kVp
      distribution of the workload data was determined and normalized per patient for
      each of the seven types of installations. The total average workload per patient
      surveyed in each type of installation is 2.5, 13, 1.5, 0.22, 6.7, 160, and 64 mA
      min per patient for the above installation types. For general radiographic rooms
      the primary beam was directed at the floor for 69% of the total workload, with
      the remaining 21.5%, 6.5% and 1.6% of the workload directed toward three walls.
      When multiplied by the average number of patients examined weekly in each type of
      installation, the mean weekly workloads observed are 270, 230, 35, 44, 320, 3100,
      and 1400 mA min for the above-listed types of installations. Additionally, a
      significant fraction of the observed workloads occur at potentials much less than
      the kVp values typically assumed for radiation shielding.

PMID- 8860906
TI  - Estimation of fractal dimension in radiographs.
AB  - In the last decade, the fractal dimension has become a popular parameter to
      characterize image textures. Also in radiographs, various procedures have been
      used to estimate the fractal dimension. However, certain characteristics of the
      radiographic process, e.g., noise and blurring, interfere with the
      straightforward application of these estimation methods. In this study, the
      influence of quantum noise and image blur on several estimation methods was
      quantified by simulating the effect of quantum noise and the effect of modulation
      transfer functions, corresponding with different screen-film combinations, on
      computer generated fractal images. The results are extrapolated to explain the
      effect of film-grain noise on fractal dimension estimation. The effect of noise
      is that, irrespective of the noise source, the fractal dimension is
      overestimated, especially for lower fractal dimensions. On the other hand,
      blurring results in an underestimation of the dimensions. The effect of blurring
      is dependent on the estimation method used; the dimension estimates by the power
      spectrum method are lowered with a constant value, whereas the underestimation by
      the methods working in the spatial domain is dependent on the given dimension.
      The influence of the MTF and noise on fractal dimension estimation seriously
      limits the comparability of fractal dimensions estimated from radiographs which
      differ in noise content or MTF. Only when the power spectrum method is used, it
      is possible to correct for the influence of different MTFs of screen-film
      combinations. It is concluded that only when using the same object-focus
      distance, the same exposure conditions, the same digitizer at the same
      resolution, can fractal dimensions as estimated in radiographs be reliably
      compared.

PMID- 8860907
TI  - An improved shift-invariant artificial neural network for computerized detection
      of clustered microcalcifications in digital mammograms.
AB  - A shift-invariant artificial neutral network (SIANN) has been applied to
      eliminate the false-positive detections reported by a rule-based computer aided
      diagnosis (CAD) scheme developed in our laboratory. Regions of interest (ROIs)
      were selected around the centers of the rule-based CAD detections and analyzed by
      the SIANN. In our previous study, background-trend correction and pixel-value
      normalization were used as the preprocessing of the ROIs prior to the SIANN. A
      ROI is classified as a positive ROI, if the total number of microcalcifications
      detected in the ROI is greater than a certain number. In this study,
      modifications were made to improve the performance of the SIANN. First, the
      preprocessing is removed because the result of the background-trend correction is
      affected by the size of ROIs. Second, image-feature analysis is employed to the
      output of the SIANN in an effort to eliminate some of the false detections by the
      SIANN. In order to train the SIANN to detect microcalcifications and also to
      extract image features of microcalcifications, the zero-mean-weight constraint
      and training-free-zone techniques have been developed. A cross-validation
      training method was also applied to avoid the overtraining problem. The
      performance of the SIANN was evaluated by means of ROC analysis using a database
      of 39 mammograms for training and 50 different mammograms for testing. The
      analysis yielded an average area under the ROC curve (A(z)) of 0.90 for the
      testing set. Approximately 62% of false-positive clusters detected by the rule
      based scheme were eliminated without any loss of the true-positive clusters by
      using the improved SIANN with image feature analysis techniques.

PMID- 8860922
TI  - State of the art on the development of the implantable hearing device for partial
      hearing loss.
AB  - This article summarizes the state of the art of the implantable hearing devices
      for partial hearing loss. Devices such as temporal bone stimulators and
      piezoelectric and electromagnetic middle and inner ear transducers are discussed.
      Cochlear implants are excluded. (See "Update on Cochlear Implantation" in this
      issue.) Those readers interested in a more in-depth study of implantable hearing
      devices should consult the February 1995 issue of The Otolaryngologic Clinics of
      North America which is dedicated to this matter (Guest Editor: Anthony J.
      Maniglia, MD).

PMID- 8860924
TI  - Otosclerosis update.
AB  - The use of lasers for primary and revision stapes surgery has many applications
      and potential advantages over mechanical techniques. It should be emphasized,
      however, that the laser is simply a tool, albeit a sophisticated one, and not a
      substitute for knowledge, experience, judgment, or ability. A laser will not
      "make" a good stapes surgeon, any more than a scalpel "makes" a good surgeon.
      There are limitations as well as benefits to lasers. Excellent results for stapes
      surgery were obtained for years prior to the advent of lasers, which is testimony
      to the skill and understanding of nonlaser stapes surgeons.

PMID- 8860923
TI  - Lasers in surgery for chronic ear disease.
AB  - This article describes specific situations in which the laser has been found to
      be useful in surgery for chronic ear disease. In the opinion of the authors, the
      most important application is the atraumatic removal of cholesteatoma from a
      mobile stapes. Additional uses include precise and hemostatic removal of diseased
      tissue (polyps, granulations, adhesions) and manipulations upon an intact
      ossicular chain without induction of vibrational trauma. Potential complications
      such as facial nerve and inner ear injury are considered.

PMID- 8860925
TI  - Iatrogenic facial nerve injury: the role of facial nerve monitoring.
AB  - Intraoperative facial nerve monitoring has emerged as a powerful tool for
      facilitation of surgery involving the facial nerve. This tool must be properly
      applied and maintained, however, in order to avoid untoward results and to
      maximize its potential benefits. Facial nerve monitoring is best suited for
      prevention of iatrogenic injury. Once injury has become established, its value
      may be severely limited, especially for moderate to severe injury, in which
      visual assessment of injury is still the most effective means to determine the
      need for repair. The most valuable derivative of facial nerve monitoring is
      enhanced awareness of the edge of the facial nerve contour. This allows strategic
      alterations in surgical technique for improved facial nerve functional
      preservation. Although facial nerve monitoring appears to have already had a
      favorable influence on facial nerve preservation, further improvement seems
      likely over time through an ongoing process of trial and error.

PMID- 8860926
TI  - Update on cochlear implantation.
AB  - Cochlear implants are computerized devices that partially replace the
      transduction and encoding functions of the cochlea. Over the past 20 years
      studies have demonstrated that cochlear implants are safe and effective, with
      modern computer-based multichannel devices providing open-set word understanding
      for the majority of implanted postlingually deafened adults as well as pre- and
      postlingually deafened children. Advances in word processing strategy have led to
      ever-improving word recognition skills and recent studies have demonstrated that
      oral language develops in congenitally deaf children who use cochlear implants.

PMID- 8860927
TI  - Endoscopic otologic surgery.
AB  - In this article, various otologic and neurotologic procedures, including middle
      ear exploration, chronic ear disease surgery, second-look mastoidectomy, acoustic
      neuroma surgery, and vestibular neurectomy, are reviewed for the usefulness of
      minimally invasive endoscopic techniques.

PMID- 8860928
TI  - Titanium-anchored prostheses in otology.
AB  - In the late 1970s, Per-Ingvar Branemark and coworkers in Goteberg, Sweden,
      successfully introduced osseointegrated titanium implants into clinical practice.
      They had achieved the previously elusive goal of producing stable, secure
      percutaneous implants anchored in underlying cortical bone. Two applications of
      these implants to otology were obvious: (1) to provide a coupling for bone
      conduction hearing aids and (2) to provide fixation points for anchoring of
      auricular prostheses. Before describing the current state of these clinical
      applications and considering future potential uses, the authors review the basis
      for titanium osseointegration.

PMID- 8860929
TI  - Surgical treatment of Meniere's disease.
AB  - Several reliable surgical procedures aimed to control the vertigo associated with
      Meniere's disease exist. Vestibular preservation and ablative procedures are
      available with the latter divided between hearing preservation and destructive
      operations. Factors to consider prior to choosing a surgical option include the
      age, health, and employment status of the patient; the degree of hearing loss in
      the involved ear; and the status of the contralateral ear.

PMID- 8860930
TI  - Particle repositioning for benign paroxysmal positional vertigo.
AB  - Benign paroxysmal positional vertigo is a common condition that can be severely
      incapacitating. The causative mechanism is usually displaced dense particles
      (canaliths) in a semicircular canal. By means of canalith repositioning, these
      particles can be moved into the utricle and the symptoms completely resolved in a
      high percentage of cases. The protocol for procedure is discussed as well as the
      management of complications and recurrences.

PMID- 8860931
TI  - Update on posterior canal occlusion for benign paroxysmal positional vertigo.
AB  - Most, if not all, cases of BPPV appear to result from free-floating posterior
      semicircular canal endolymph particles. Particle repositioning alleviates
      symptoms and findings in the vast majority of patients. For the small intractable
      group of nonresponders, posterior semicircular canal occlusion remains a safe and
      highly efficacious procedure. This new technique has also paved the way for even
      newer and most invasive inner ear procedures.

PMID- 8860932
TI  - Update on idiopathic perilymphatic fistulas.
AB  - Idiopathic perilymphatic fistula has been confirmed with clinical-temporal bone
      histopathologic studies as a separate inner ear disease. Criteria for its
      diagnosis are sudden or progressive sensory hearing loss, or for vestibular
      components, a positive fistula test, constant disequilibrium, and positional
      nystagmus or postural vertigo. Nonsurgical treatment, such as keeping the head
      higher than the heart and avoiding heavy lifting, can be tried. When it is
      ineffective or when there is sudden hearing loss without improvement, surgical
      sealing of the leak should be attempted.

PMID- 8860933
TI  - Dexamethasone perfusion of the labyrinth plus intravenous dexamethasone for
      Meniere's disease.
AB  - Recent clinical and laboratory evidence indicates that Meniere's disease is an
      immune-mediated disease. Dexamethasone perfusion of the inner ear through the
      round window plus intravenous dexamethasone often will stop the dizzy spells,
      reduce the fullness and low-frequency tinnitus, and sometimes improve the hearing
      in patients with Meniere's disease. The dexamethasone must act mostly on the
      endolymphatic sac and, to a lesser extent, on the stria vascularis and spiral
      ligament, the known targets of immune response in the inner ear, to reduce the
      endolymphatic hydrops and restore the fluid dynamics of the endolymph. Despite
      the good results with streptomycin perfusion, the number of patients with further
      hearing loss is large, so dexamethasone perfusion with intravenous dexamethasone
      should be tried first. The initial response to dexamethasone perfusion plus
      intravenous dexamethasone has been very good, with very little risk of further
      hearing loss, and it holds great promise for the future.

PMID- 8860934
TI  - Update on vestibular rehabilitation therapy.
AB  - Although the concept of using exercises as part of the treatment for patients
      with persistent vertigo was introduced several decades ago, organized vestibular
      rehabilitation therapy programs have only recently been introduced. These
      programs typically involve a three-pronged approach, customized to the needs of
      the individual patient: (1) habituation exercises designed to facilitate central
      nervous system compensation by extinguishing pathologic responses to head motion,
      (2) postural control exercises, and (3) general conditioning activities. This
      article provides an update regarding the status of vestibular rehabilitation,
      reviewing the concept of vestibular compensation and patient selection criteria
      for current rehabilitative techniques.

PMID- 8860935
TI  - Computerized graphic imaging for three-dimensional representation: general
      principles and applications to embryo/fetal development.

PMID- 8860936
TI  - Morphometric analysis of vascular smooth muscle cells by scanning electron
      microscopy.
AB  - The information presented in this chapter clearly shows the usefulness of SEM for
      analyzing the components of the wall of microvessels. The literature contains
      several methodologies that allow one to successfully expose single smooth muscle
      cells that line microvessels. It appears that chemical and enzymatic digestion
      steps will continue to be the principal elements of any methodology for exposing
      these cells. The combination of microdissection, prior to processing the specimen
      for SEM, with digestion has allowed better preservation of the tissues by
      reducing the amount of material obscuring the tissue of interest as well as
      reducing the length of time the tissue is exposed to chemicals. The next
      important improvement was the mobilization step of selected vessel segments so
      that they could be mounted "end on" for circumferential viewing and
      photographing. Finally, at least three different mathematical approaches have
      been developed and tested for the quantitation of single cell length and width
      determination.

PMID- 8860938
TI  - In vivo confocal imaging.

PMID- 8860937
TI  - Three-dimensional confocal light and electron microscopy of central nervous
      system tissue and neurons and glia in culture.

PMID- 8860939
TI  - Tandem scanning confocal microscopic imaging of the living kidney.

PMID- 8860940
TI  - In situ studies of renal arteriolar function using the in vitro-perfused
      hydronephrotic rat kidney.
AB  - A method of examining arteriolar function in situ using the in vitro-perfused
      hydronephrotic rat kidney is described. This approach facilitates direct
      visualization of arteriolar contractile responses in a well-controlled
      experimental environment while avoiding the consequences of traumatic
      microdissection and the accompanying exposure to ischemia, hypothermia, or
      hypoxia. The preparation has a remarkably well-preserved myogenic reactivity,
      exhibiting precisely graded vasoconstriction over the range in perfusion pressure
      subtending normal renal autoregulatory responses (i.e., 80-180 mm Hg). Using this
      preparation, the inhibitory effects of hypoxia on arteriolar myogenic reactivity
      have been demonstrated. The range over which reduced pO2 affected arteriolar
      reactivity in this model corresponded closely to that reported to alter vascular
      tone in vivo. A technique of adapting the model to incorporate simultaneous
      monitoring of arteriolar fluorescence measurements and contractile responses is
      also described. This approach has been used to examine the relationship between
      arteriolar contractility and NADH autofluorescence during the hypoxia-induced
      activation of ATP-sensitive K channels. Future applications may include the use
      of intravital fluorescent dyes to examine, for example, microvascular endothelial
      calcium signaling in an intact, functioning arteriole.

PMID- 8860941
TI  - Optical studies of intracellular pH in kidney cells in vitro.

PMID- 8860942
TI  - Simultaneous imaging of intracellular [Ca2+] and pH in single cells.

PMID- 8860943
TI  - Measuring cytosolic Ca2+ in cells with fluorescent probes: an aid to
      understanding cell pathophysiology.

PMID- 8860944
TI  - Glycation index of hair for non-invasive estimation of diabetic control.
AB  - We propose a new indicator for diabetic control that shows the extent of
      glycation of hair protein (keratin), the glycation index (A(390)/A(412)) which is
      based on the ratio of glycated protein- to cystine-induced coloration, where
      A(390) and A(412) represent each absorbance in the color reactions of glycated
      protein and cystine in the hair protein. Samples can be quickly and non
      invasively collected and easily stored. This index for the back and scalp hairs
      from hypercholesterolemic mice with hyperglycemia, diabetic rats and diabetic
      patients gave significantly higher values (2.0-6.0-fold) than those of normal
      subjects (p<0.01). The glycation indices (mean + or - S.D.) of hairs from
      diabetic and non-diabetic subjects were 3.00 + or - 0.96 (n = 21) and 1.51 + or -
      0.45 (n = 30), respectively. These indices (y) correlated well with the levels of
      glycohemoglobin (HbA(1c), chi) in diabetic and non-diabetic subjects: y = 0.69
      chi- 2.03 (r = 0.82, n = 31, p<0.01). Within-run precision (reproducibility, CV)
      for the assay of the glycation indices of hairs from the three groups was 6.7
      9.4% (n = 10 each). The proposed glycation index of hair gave reasonable results
      for animals and humans with normo- and hyperglycemia, suggesting that it is
      reliable and can be diagnostically useful.

PMID- 8860945
TI  - Separation and characterization of monoglucuronides of vitamin D(3) and25
      hydroxyvitamin D(3) in rat bile by high-performance liquid chromatography.
AB  - The separation and characterization of vitamin D(3)- and 25-hydroxyvitamin D(3)
      monoglucuronides, biliary metabolites obtained from rats dosed with D(3) and 25
      hydroxyvitamin D(3) per os, respectively, were carried out by HPLC. The
      glucuronide fractions were obtained from bile specimens by the combined use of a
      Bond Elut C18 cartridge, for solid phase extraction, and a lipophilic gel
      (piperidinohydroxypropyl Sephadex LH-20), for ion-exchange chromatography. Each
      glucuronide was identified by comparison with an authentic sample in three ways:
      its chromatographic behavior, that of its fluorescent labeled derivative using 4
      [4-(6-methoxy-2-benzoxazolyl)phenyl]-1,2,4-triazoline-3,5- dione and data
      obtained following enzymatic hydrolysis using beta-glucuronidase.

PMID- 8860946
TI  - Effects of biscoclaurine alkaloid cepharanthine on newborn rat skin epidermal and
      dermal cells.
AB  - Effects of biscoclaurine alkaloid cepharanthine on proliferation of skin cells
      were examined in vitro. The alkaloid was found to enhance attachment and cell
      layer formation of newborn rat skin epidermal cells in culture on type I collagen
      coated Millipore filter, and to potentiate production of keratins in these cells.
      Spreading and growth of skin dermal fibroblasts were inhibited by cepharanthine
      in a dose-dependent manner, but the alkaloid-treated cells still retained the
      ability to synthesize type IV collagen. In culture of skin cells containing both
      epidermal and dermal cells, no growth of epidermal cells or over-growth of dermal
      fibroblasts was observed in medium without cepharanthine. In contrast, the
      presence of the alkaloid suppressed the growth of fibroblasts and promoted the
      formation of epidermal cell layers accompanied by production of keratins. Thus,
      in comparison with the cells untreated with the alkaloid, cepharanthine-treated
      skin epidermal and dermal cells in vitro expressed in vivo-like characters.

PMID- 8860947
TI  - Effect of culture matrix on newborn rat skin basal cells; modification of cell
      response to extracellular calcium.
AB  - Basal cells from newborn rat skin epidermis were cultured on various culture
      matrixes, and the response of the cells to extracellular calcium was examined.
      When the cells were cultured on a type I collagen-coated Millipore filter to
      maintain clearance under the cultured cells as intact skin, the cells responded
      to a fluctuation in extracellular calcium and were detached from the collagen
      layer in a high calcium environment. In this case, protein synthesis of the cells
      increased calcium-dependently. In contrast, calcium-dependent protein synthesis
      of the cells was not detected in culture, neither on the plastic plate nor the
      type I collagen-coated plate. Moreover, in culture on a type I collagen-coated
      filter, the size of basal cells was unchanged for 2 d. This should be consistent
      with the fact that morphological changes in cells are very gradual in vivo. On
      the other hand, when basal cells were cultured either on a plastic plate or
      collagen-coated plate, the cells lost their normality; they were markedly
      enlarged for 2d of culture. Thus, the responses of skin basal cells to
      extracellular calcium fluctuated according to the types of culture matrixes. In
      this case, keratin synthesis and a morphological change of the cells seems to be
      concerned with the clearance, which was established in the basal side of the
      cultured basal cells as intact skin.

PMID- 8860948
TI  - Characterization of cyclophilin 40: highly conserved protein that directly
      associates with Hsp90.
AB  - Cyclophilin 40 (CyP4O) is a recently identified member of the cyclophilin family
      that may be a component of unactivated steroid receptor complexes. It consists of
      an N-half portion that is highly homologous to cyclophilin A and has peptidyl
      prolyl isomerase (PPIase) activity, and a C-half portion that resembles the C
      terminal portion of FKBP52 (FK506 binding protein 52), another component of
      unactivated steroid receptor complexes. To better understand the structure and
      functional characteristics of this new class of cyclophilin, we have raised
      monoclonal antibodies against the C-half portion of human CyP4O. Immunostaining
      with the antibodies showed its preferential localization in cytoplasm. One
      antibody cross-reacted with a 45 kDa protein in yeast, suggesting high
      conservation throughout evolution. A CyP4O-associated protein was isolated from
      rabbit reticulocyte lysate by means of an affinity resin, and was identified as
      hsp90. The C-half portion of CyP4O was necessary and sufficient for the
      interaction.

PMID- 8860949
TI  - Sex differences in constitutive level of renal lauric acid hydroxylase activities
      and CYP4A-related proteins in mice.
AB  - The constitutive level of renal fatty acid hydroxylase was examined in ddY mice
      by measuring the activities of lauric acid omega- and (omega-1)-hydroxylase,
      (LA12H and LA11H respectively). The activities of both LA12H and LA11H of male
      mice were significantly higher than those of female mice. This sex difference in
      renal lauric acid hydroxylase (LAH) activity exists in other strains of mice,
      including Balb/c, C57BL/6, C3H/HeN and C3H/HeJ. Renal LAH activities are at
      significantly low levels in both sexes of immature animals, but are sexually
      differentiated in the mature state. In male mice, orchiectomy caused a drastic
      decrease in renal LAH activities, and the activities were restored by
      testosterone treatment to above the level of the intact animal. In female mice,
      ovariectomy and estradiol treatment had no effect on the activities, but
      testosterone treatment caused an increase in the activities to the level of the
      intact male animal. These results suggested that testosterone is a key regulatory
      factor in the level of LAH activity in mouse kidney. The administration of
      dexamethasone and clofibrate affected the level of LAH activity. The above data
      are consistent with the level of CYP4A-related proteins (band H and L protein)
      measured by using anti-rat CYP4A1 antibodies.antibodies. The antibodies inhibited
      both LA12H and LA11H activities. The level of band H protein was regulated by
      testosterone and dexamethasone. On the other hand, the level of band L protein
      was regulated by clofibrate. These results suggest that distinct modes of
      regulation exist in the level between band H and L protein in mouse kidney.

PMID- 8860950
TI  - Cell-density-dependent expression of the alpha(2)-adrenergic response by
      epidermal growth factor (EGF) in primary cultures of adult rat hepatocytes.
AB  - Effects of epidermal growth factor (EGF) on the expression of alpha(2)-adrenergic
      responses were examined in primary cultures of adult rat hepatocytes. The
      alpha(2)-responses were assessed by the inhibition of the rate of forskolin
      stimulated cAMP formation by the selective alpha(2)-adrenergic agonists,
      oxymetazoline and UK-14304. Hepatocytes cultured with EGF (20 ng/ml) at a high
      cell density (1.0 x 10(5)/cm2) showed almost no response to the alpha(2)
      adrenergic agonists, oxymetazoline and UK-14304 (1-100 mu M). In contrast, when
      cultured at a low cell density (3.3 x 10(4) cells/cm2) with EGF, forskolin
      stimulated cAMP production was inhibited by oxymetazoline and UK-14304 in a dose
      dependent manner. The alpha(2)-response was blocked by the alpha2-antagonist
      yohimbine (10 mu M). It was also reversed by treatment of hepatocytes with
      pertussis toxin (100 ng/ml). In addition, the effects of EGF on the appearance of
      alpha(2)-responses were almost completely inhibited by treatment of the
      hepatocytes with genistein (10 mu M) or cytochalasin B (10 mu M). The alpha(2)
      response was abolished when cycloheximide (5 mu M) was added to the cultures.
      These results demonstrate that when cultured at a low cell density with EGF,
      adult rat hepatocytes acquire a significant alpha(2)-adrenergic response. The
      expression of this alpha(2)-response is associated with de novo protein
      synthesis.

PMID- 8860951
TI  - Effects of ethanol on phospholipases in the mouse brain, heart and liver.
AB  - The activities of microsomal phospholipase A(2) (PLA(2)) and C (PLC) from mouse
      brain, heart and liver were determined using the substrate 1-palmitoyl-2-N-(4
      nitrobenzo-2-oxa-1,3-diazole amino caproyl-phosphatidylcholine (NBD-PC), and the
      effects of chronic ethanol treatment (ethanol) as well as in vitro addition of
      various n-alcohols including ethanol on these activities were evaluated.
      Microsomal membrane fluidity was estimated by diphenylhexatriene anisotropy
      (gamma). The microsomes from the brain and heart of ethanol-treated mice showed
      significantly higher PLA(2) activity than those from controls. The brains of
      ethanol group showed significantly higher PLC activity, while the heart showed
      significantly lower PLC activity than those of controls. The microsomes from the
      brain and heart of ethanol-treated mice showed significantly reduced gamma values
      compared to those of controls. The addition of ethanol in vitro to microsomes was
      found to increase PLC activity in these tissues, while it decreased PLA(2)
      activity in a dose-dependent manner. The other n-alcohols showed similar effects
      on PLA(2) and PLC activity in the live microsomes, while decreases were observed
      the gamma values in a dose-dependent manner. These results suggest that the
      change in the membrane fluidity associated with addition of alcohols is a
      prerequisite for the changes in PLA(2) and PLC activities. In addition, our
      findings suggest that these changes may play a major role in the cellular injury
      associated with chronic ethanol treatment in the mouse.

PMID- 8860952
TI  - Acceleration of wound healing in diabetic mice by basic fibroblast growth factor.
AB  - We studied the effect of recombinant human basic fibroblast growth factor (bFGF)
      on wound healing in genetically diabetic mice. Wound closure after full-thickness
      excision of skin was markedly delayed in diabetic mice compared to normoglycemic
      mice. A single application of bFGF caused a marked acceleration of wound healing
      in a dose-dependent manner. There were no hypertrophic scars or unlimited
      granulation tissue formation in regenerated tissues treated with any doses of
      bFGF under histological examination. The repeated application of bFGF for 7 d
      showed a bell-shaped dose-response in the rate of wound closure, and the optimal
      dose was as small as 0.2-2 mu g per wound. Reduced angiogenesis and granulation
      tissue formation were observed in diabetic mice compared to normal mice, and bFGF
      treatment restored both responses to significant levels. The beneficial effect of
      bFGF on wound healing would be largely explained by enhanced angiogenesis and
      granulation tissue formation.

PMID- 8860953
TI  - A high linoleate and a high alpha-linolenate diet induced changes in learning
      behavior of rats. Effects of a shift in diets and reversal of training stimuli.
AB  - Rats fed from weaning on semi-purified diets supplemented either with linoleate
      rich safflower oil (S) or alpha-linolenate-rich perilla oil (P) were mated. Half
      of the progeny were weaned to the original diet of the dams (SS and PP), the
      other two groups were shifted to diets enriched in the other fatty acid (SP and
      PS). Brightness-discrimination learning ability was tested daily for 30 d
      beginning at 11 weeks of age, with a bright light as the positive stimulus. The
      learning performance was inferior in the group fed the safflower diet through two
      generations (SS) as compared with groups fed the perilla diet through two
      generations (PP) or for which the diets were shifted at weaning (PS and SP). The
      docosahexaenoate content of brain phospholipids was significantly less in the SS
      group compared with the three other groups. After 30 d of the learning test, the
      effect of shifting the stimulus was tested for another 30 d, this time using a
      dim light as the positive stimulus. The learning performance was superior in the
      PP group to the SS group throughout the latter 30 sessions, the difference being
      even more obvious than during the first 30 d. These results indicate that the
      decrease in the discrimination-learning ability induced by alpha-linolenate
      deficiency is a relatively reversible process; both the docosahexaenoate content
      in brain and the learning performance were restored by supplementing alpha
      linolenate after the weaning.

PMID- 8860954
TI  - Potent mutagenic potential of 4-methylquinoline: metabolic and mechanistic
      considerations.
AB  - 4-Methylquinoline (4-MeQ) showed an extraordinarily potent mutagenicity when
      compared to quinoline and isomeric methylquinolines. The major metabolite of 4
      MeQ was 4-hydroxymethylquinoline, which was not mutagenic under the assay
      condition employed. Deuteration of the methyl group of 4-MeQ resulted in a
      decrease in the amount of the hydroxymethyl metabolite and an increase in
      mutagenicity, indicating that hydroxylation of the substituent methyl group is a
      detoxication process. A 3-chloro derivative of 4-MeQ was proven to be non
      mutagenic. 4-Ethyl-quinoline, as well as 4-hydroxymethylquinoline, was much less
      mutagenic than 4-MeQ. Taking account of the structure-mutagenicity relationship,
      a possible mechanism is proposed for the potent mutagenic potential of 4-MeQ.

PMID- 8860955
TI  - Apolipoprotein B inhibits the hemolytic activity of asp-hemolysin from
      Aspergillus fumigatus.
AB  - We investigated the effect of human blood plasma lipoproteins on the hemolytic
      activity of Asp-hemolysin. Apolipoprotein B (apoB)-containing lipoproteins, such
      as low density lipoprotein (LDL) and very low density lipoprotein (VLDL), inhibit
      the activity of this hemolytic toxin. When Asp-hemolysin (15 mu g) was incubated
      with 100 mu g LDL (as protein), the hemolytic activity was inhibited by 90%. When
      20 mu g apoB was added, the hemolytic activity was almost completely inhibited.
      Furthermore, similar inhibition was obtained in the filtrates which were
      separated from the incubation mixture of Asp-hemolysin with LDL or apoB following
      ultrafiltration through a membrane with a molecular cutoff = 100000. The current
      findings suggest that the inhibition by LDL is due to apoB binding to Asp
      hemolysin.

PMID- 8860956
TI  - Dimethylarsenics reveal DNA damage induced by superoxide anion radicals.
AB  - We previously reported that DNA single-strand breaks (ssb) induced by exposure to
      dimethylarsinic acid (DMAA) were enhanced by the presence of paraquat (PQ), a
      superoxide anion radical 0 -(2)-producing agent, in cultured human alveolar type
      II (L-132) cells in vitro. In the present study, we examined the effect of
      sequential exposure of the cells to PQ and then DMAA under conditions causing no
      ssb by each alone, and observed a remarkable occurrence of ssb. The result
      suggests that 0 -(2) caused DNA damage, which became detectable as ssb by the
      treatment using DMAA. The DNA damage induced by the exposure to PQ alone was
      different from that by DMAA; PQ-induced damage was fully repaired after 24 h,
      while DMAA-induced damage was repaired only partially, and aphidicolin, an
      inhibitor of repair-serving DNA polymerases alpha, delta and/or epsilon,
      inhibited only the latter repair but not the former. These findings indicate that
      the DMAA treatment may be an effective tool to reveal DNA damage induced by 0 
      (2), which to date has not been sufficiently clarified.

PMID- 8860957
TI  - Effect of rapeseed and dietary oils on the mean survival time of stroke-prone
      spontaneously hypertensive rats.
AB  - Low-fat conventional diets supplemented with 5 or 10% vegetable oils were fed to
      stroke-prone spontaneously hypertensive rats (SHR-SP) from weaning and the mean
      survival times were determined. A 1% aqueous sodium chloride solution was used as
      drinking water throughout the experiments. In four separate experiments, the
      rapeseed oil group showed a significantly shorter mean survival time. The
      relative mean survival times were 50-59% (rapeseed oil group), 78-100% (soybean
      oil group) and 86% (microbial oil group) as compared with the group fed perilla
      oil (100%). The group which received 4-fold diluted rapeseed oil exhibited a
      significantly shorter survival time as compared with the group receiving soybean
      oil. Although the feeding experiments were performed under very simple and
      restricted conditions, these results suggest that the rapeseed oil prepared for
      human use contains a factor (s) which is toxic to SHR-SP rats.

PMID- 8860958
TI  - Effect of plant phenolics on the formation of the spin-adduct of hydroxyl radical
      and the DNA strand breaking by hydroxyl radical.
AB  - The effect of plant phenolics, including flavonoids and green tea polyphenolics,
      on hydroxyl radical was examined by a common method using an electron spin
      resonance (ESR) technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin
      trapping agent. The intensity of the ESR signals of DMPO-OH adduct formed by the
      interaction of DMPO with Fenton reagent was reduced in the presence of each
      phenolic in a dose-dependent manner. However, the decrease in the intensity of
      the signals was due partly to the enhanced disappearance of the spin adduct by
      the phenolics, as has been previously shown. This spin trapping method was
      unreliable for evaluation of the effect of the phenolics against hydroxyl
      radical. Hydroxyl radical induced-DNA single-strand breaks may be a better index
      for evaluation of the activity of the phenolics regarding hydroxyl radical. The
      effect of the phenolics on DNA single-strand breaks induced by Fenton reagent was
      examined. While sesamol and esculetin were inhibitory, most polyphenolics,
      especially (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG),
      were rather stimulatory. The results indicate that sesamol and esculetin
      scavenged hydroxyl radical, and EGC and EGCG generated hydroxyl radical under the
      conditions where hydroxyl radical was generating.

PMID- 8860959
TI  - Cytotoxic activities of solanum steroidal glycosides.
AB  - Cytotoxic activities of 20 steroidal glycosides obtained from Solanum genera
      plants were examined against various cell lines to provide new evidence as
      follows: 1) As regarding the sugar linkage, the glycosides possessing a beta
      chacotriosyl moiety were the most effective and the presence of the terminal
      rhamnosyl residue was required for exhibiting strong activity. 2) As for the
      aglycone, the glycosides carrying a spirostanol aglycone showed the strongest
      activity and even an aglycone without a sugar linkage presented considerably
      strong activity.

PMID- 8860960
TI  - Protective effect of celosian, an acidic polysaccharide, on chemically and
      immunologically induced liver injuries.
AB  - Hepatoprotective effect of celosian, an acidic polysaccharide isolated from the
      water extract of the seed of Celosia argentea, was investigated using chemical
      and immunological liver injury models. Celosian inhibited the elevation of serum
      enzyme (GPT, GOT, LDH) and bilirubin levels on carbon tetrachloride (CC1(4))
      induced liver injuries in rat. In addition, the hepatoprotective effect of
      celosian was also observed in this model of liver injury by histopathological
      findings. Moreover, celosian suppressed rises in GPT or mortality on fulminant
      hepatitis induced by D-galactosamine/lipopolysaccharide (D-Ga1N/LPS) or
      Propionibacterium acnes/LPS in mice. These findings suggested that celosian is an
      active component in protection against chemical and immunological hepatitis and
      the activity was found to be a dose dependent. Celosian showed a concentration
      dependent inhibitory effect on lipid peroxide (LPO) generation in vitro. Though
      celosian did not reduce the release of tumor necrosis factor-alpha (TNF-alpha),
      it protected against recombinant human TNF-alpha (rhTNF-alpha)-induced liver
      injury in D-galactosamine sensitized mice.

PMID- 8860961
TI  - Inhibitory effects of sterols isolated from Chlorella vulgaris on 12-0
      tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse
      skin.
AB  - Inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      inflammation in mice was observed in the methanol extract of Chlorella vulgaris,
      a green alga. The hexane soluble fraction obtained from the methanol extract
      exhibited marked inhibitory activity from which were isolated two delta(5,7)
      sterols (ergosterol and 7-dehydroporiferasterol), two delta(5,7,9(11))-sterols
      [7,9(11)-dehydroergosterol and 7,9(11)-bisdehydroporiferasterol], two 5 alpha, 8
      alpha-epidioxy-delta(6)-sterols (ergosterol peroxide and 7-dehydroporiferasterol
      peroxide), and a 7-oxo-delta(5)-sterol (7-oxocholesterol), among others. The
      delta 5'7-sterols, 5 alpha, 8 alpha-epidioxy-delta(6)-sterols and 7-oxo-delta 5
      sterol inhibited TPA-induced inflammation in mice. The 50% inhibitory dose of
      these compounds for TPA-induced inflammation was 0.2-0.7 mg/ear. Furthermore,
      ergosterol peroxide markedly inhibited the tumor-promoting effect of TPA in 7,12
      dimethylbenz[a]anthracene-initiated mice.

PMID- 8860962
TI  - Restriction fragment length polymorphisms of rDNA and variation of essential oil
      composition in Atractylodes plants.
AB  - Total DNA was extracted from the leaves of Atractylodes lancea DE CANDOLLE, A.
      ovata DE CANDOLLE and A. japonica KOIDZUMI ex KITAMURA of various origins and
      hybridized with digoxigenin-labeled rice ribosomal DNA after digestion with eight
      different restriction endonucleases. The resulting restriction fragment length
      polymorphism (RFLP) profiles allowed us to distinguish the three Atractylodes
      species when DNA was digested with Sac I. Although atractylon was detected in the
      rhizomes of some of the cultivated strains of A. lancea, their RFLP profiles
      clearly indicate that these plants are not hybrids of A. ovata or A. japonica.
      RFLP analysis also revealed the presence of intraspecific variation in DNA
      sequence of rRNA locus among A. lancea as well as A. japonica.

PMID- 8860963
TI  - Uptake mechanism of fractioned [(3)H]heparin in isolated rat kupffer cells:
      involvement of scavenger receptors.
AB  - The uptake of fractionated [(3)H]heparin was examined to elucidate the uptake
      mechanism in isolated rat Kupffer cells. The equilibrium binding of fractionated
      [(3)H]heparin to Kupffer cells was concentration-dependent with the dissociation
      constant of 5.7 nM and the maximum binding capacity of 1.5 pmol/10(6) cells.
      Several ligands of scavenger receptors inhibited the binding of fractionated
      [(3)H]heparin to Kupffer cells competitively and also the internalization of
      heparin, suggesting the involvement of scavenger receptors in the uptake of
      fractionated [(3)H]heparin. Fractionated [(3)H]heparin was also suggested to be
      internalized according to first order kinetics with the apparent internalization
      rate constant of 0.010 min (-1). Lowering temperature from 37 to 4 degrees C
      reduced the fraction internalized from 33% to 6% without affecting the total
      association, while the fraction internalized at 25 degrees C was comparable with
      that at 37 degrees C. Metabolic inhibitors (2,4-dinitrophenol and rotenone), an
      inhibitor of receptor-mediated and adsorptive endocytosis of polypeptides
      (phenylarsine oxide) and phagocytosis inhibitors (cytochalasine B and colchicine)
      did not inhibit the internalization of fractionated [3(H)]heparin. As known
      inhibitors of receptor-mediated and adsorptive endocytosis of polypeptides and
      phagocytosis did not affect the uptake of fractionated heparin, the scavenger
      receptor-mediated uptake is suggested to be ATP-independent and different from
      receptor-mediated and adsorptive endocytosis of polypeptides and phagocytosis,
      although for temperature dependency it showed the typical characteristics of
      receptor-mediated endocytosis.

PMID- 8860964
TI  - Effects of a prescription of Chinese herbal medicine on snake venom-induced
      nephropathy in mice.
AB  - A prescription of Chinese herbal medicine, tentatively named P-19, was examined
      for its inhibitory effect and its mechanism using an experimental model of
      nephropathy induced by purified snake venom proteinase, Ac(1)-proteinase (Ac(1)
      P). The treated mice were injected with 0.1 ml of crude extract of P-19
      intraperitoneally every other day beginning 2 d before to 1 week after the
      injection of Ac(1)-P. The non-treated mice were injected with saline instead of
      the medicine P-19. The physiological condition and histopathological observation
      of the mice at one week after Ac(1)-P injection were better in the treated group
      than in the non-treated group. This indicates that P-19 inhibited the production
      of glomerular lesions induced in mice by Ac(1)-P. The physiological condition and
      histopathological changes in the mice were better with P-19 treatment than with P
      3 treatment. Differences in the mechanism of action between the crude extract of
      P-3 and P-19 are not only in diuretic action but also in the changes in the
      glomerular basement membrane. On the basis of spectrophotometric studies,
      phenolic carboxylates were confirmed to be contained in the crude extract of P
      19, having a different chemical structure of caffeic acid, which is the effective
      component in P-3. Immunohistochemical observation revealed a difference between
      the groups. In the non-treated mice, deposits of the venom were clearly observed
      in the glomerular tuft and Bowman's capsule, corresponding to the
      histopathological changes, within 2.5 min after the injection of Ac(1)-P. In the
      treated mice, the deposits were indistinct in the Bowman's capsule. The
      difference was considered to be caused by changes in the glomerular basement
      membrane after P-19 treatment.

PMID- 8860965
TI  - Involvement of CYP2E in 8-hydroxylation of theophylline in mouse hepatic
      microsomes-difference from its N-demethylations.
AB  - We examined which cytochrome P-450 (P-450) species other than CYP1A participates
      in the oxidative metabolism of theophylline (TP) in mouse hepatic microsomes.
      Among the three metabolic pathways of TP, only 8-hydroxylation was selectively
      enhanced by acetone, a potent inducer of CYP2E. We assumed that two P-450
      populations with different metabolic ability were involved in this metabolic
      process, and kinetic analyses revealed that the enhancement was due to the
      induction of a high-capacity P-450 population. The 8-hydroxylation at a substrate
      concentration, where most of the total activity was attributed to the catalysis
      of the high-capacity phase, was markedly impaired by CYP2E inhibitors such as 4
      methylpyrazole and aminoacetonitrile, whereas the N-demethylations were little
      affected by these agents. The activity of TP 8-hydroxylation was significantly
      correlated with that of p-nitrophenol hydroxylation, a probe for CYP2E, in
      untreated microsomes. The activities of these oxidative reactions were modified
      to a similar degree by known enzyme inhibitors with a range of inhibitory
      potencies and affinity for P-450 isoforms. On the other hand, a relationship
      between TP N-demethylations and p-nitrophenol hydroxylation was not apparent, but
      there was a behavioral similarity between the two types of N-demethylations. The
      results indicated that TP 8-hydroxylation, which accounts for a large portion of
      TP oxidations, involves CYP2E, and that its N-demethylations are mediated by a
      common or closely similar P-450 species distinct from CYP2E.

PMID- 8860966
TI  - Intestinal absorption and first-pass elimination of 2', 3'-dideoxynucleosides
      following oral administration in rats.
AB  - Intestinal absorption and first-pass elimination of 2',3'-dideoxynucleosides
      (ddNs), including 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (DDI)
      and 2',3'-didehydro-3'-deoxythymidine (D4T), following oral administration was
      investigated in rats. Enzymatic degradation of ddNs in rat intestinal washing and
      in the intestinal homogenate showed them to be stable in the washing with half
      lives of more than 140 h, whereas degradation of DDI in the intestinal homogenate
      was more than ten times as rapid as those of AZT and D4T. Intestinal absorption
      was studied in three segments of the rat intestine (duodenum, jejunum and colon)
      using an in situ closed-loop method. The area under plasma ddN concentration
      curve (AUC) and the residual percent of dose 1 h after dosing indicated a greater
      absorption of AZT and D4T in the upper intestinal tract than in the colon, very
      poor absorption of DDI in all segments, and considerable absorption of AZT in the
      colon. The AUC and the mean residence time (MRT) of ddNs following four different
      routes (intravenous: i.v., intra portal vein: i.p.v., intra duodenal: i.d. and
      intra gastric: i.g.) were measured using the in viva multiple sites of input
      method in rats. AZT and D4T were rapidly absorbed from the gastrointestinal tract
      and their bioavailability was more than 90%. DDI was less absorbed (33.02%)
      following i.d. administration compared with AZT and D4T. This poor absorption of
      DDI was partly attributable to its metabolism in the intestine.

PMID- 8860967
TI  - Evaluation of the fractional absorption of D-xylose by analysis of
      gastrointestinal disposition after oral administration in rats.
AB  - As an efficient method for estimating the amount orally absorbed, the fraction of
      D-xylose absorbed in rats was estimated from the ratio of the fecally excreted
      proportion of D-xylose dose to that of polyethylene glycol (PEG) 4000 as a
      nonabsorbable marker (D-xylose/PEG 4000 ratio). The D-xylose/PEG 4000 ratio was
      demonstrated to be independent of the fecal excretion of D-xylose and PEG 4000
      (or sampling period), suggesting that it can represent the fraction of the total
      dose remaining. This result was consistent with the theoretical prediction based
      on the assumptions that every small fraction of dose behaves in the same manner
      with regard to absorption and transit through the absorption site (small
      intestine), and that the gastrointestinal transit of PEG 4000 is identical with
      that of D-xylose. The fraction of D-xylose absorbed was estimated to be 95.9% by
      subtracting the remaining fraction (D-xylose/PEG 4000 ratio) from unity (100%).
      The D-xylose/PEG 4000 ratio, or drug/marker ratio in general, can be determined
      before fecal excretion is completed. Thus it can provide an efficient way for
      estimating the fraction of a drug absorbed that is stable in the gastrointestinal
      tract, such as D-xylose. Although this proposed method of estimating a fraction
      is generally not applicable unless a given drug is proved to be stable in the
      gastrointestinal tract, it can be an efficient screening method to identify
      poorly absorbable drugs. It is especially useful in basic studies and preclinical
      tests in laboratory animals.

PMID- 8860968
TI  - Effect of beta-glucans on the nitric oxide synthesis by peritoneal macrophage in
      mice.
AB  - Nitric oxide (NO) is an important effector molecule on antimicrobial and
      antitumor effects of macrophages. (1 -> 3)-beta-D-Glucan (beta-glucan) is well
      known to show various immunopharmacological effects such as antimicrobial effect
      and antitumor effect by activating various points of host defense mechanisms.
      This paper deals with NO synthetic activity of peritoneal macrophage (PM) induced
      by beta-glucan administration in mice. The activity was determined by measuring
      NO concentration in PM culture by Griess reagent after 24 or 48 h in vitro
      culture. Administration (i.p. or i.v.) of a branched soluble (1 -> 3)-beta-D
      glucan, grifolan (GRN), from Grifola frondosa enhanced NO synthesis of PM dose
      and time dependently. The activity was abrogated by the addition of N(G)
      monomethyl-L-arginine (L-NMMA) in vitro. The most significant activity was
      observed at 3-7 d after the administration of GRN (250 mu g/mouse). PM from all
      strains of ICR, C3H/HeN, C3H/HeJ, BALB/c, BALB/c nu/nu, C57BL, and AKR mice
      showed significant activity by GRN administration. Among beta-glucans tested, SSG
      and OL-2, highly branched soluble glucans, and a particulate beta-glucan,
      zymosan, showed similar activity. Addition of GRN directly to in vitro RAW 264.7
      or proteose peptone induced peritoneal macrophage (PP-PEC) culture could not
      enhance NO synthesis. However, NO synthesis of PP-PEC was enhanced in vitro by
      addition of GRN in the presence of interferon gamma (IFN gamma). Gene expression
      of IFN gamma mRNA in the liver and PEC were enhanced in GRN administered mice
      assessed by reverse transcriptase assisted PCR (RT-PCR) method. These facts
      strongly suggested that beta-glucan has capacity to enhance NO synthesis of PM in
      vivo through IFN gamma mediated mechanism.

PMID- 8860969
TI  - Protective activity of rabbit polyclonal anti-idiotype antibody against
      Leptospira interrogans infection in hamsters.
AB  - We prepared an anti-idiotype (Id) antibody against leptospirosis. Serum from
      rabbit immunized with monoclonal antibody (MAb) LW2, which reacted to the main
      protective antigen prepared from Leptospira interrogans serovar lai, inhibited
      agglutination of the organism by MAb LW2. The immune rabbit serum was applied to
      a column coupled with normal mouse IgG as a ligand (first column), and the
      unbound fraction eluted was applied to a column coupled with MAb LW2 as a ligand
      (second column). The bound fraction (anti-Id antibody) eluted from the second
      column inhibited the binding of MAb LW2 to sonicated leptospiral cells in ELISA.
      Mice produced antibodies against Leptospira by intraperitoneal immunization with
      the anti-Id antibody at doses of 2 mu g/mouse or more. Hamsters were protected by
      immunization with the anti-Id antibody at doses of 2 and 20 mu g/hamster from the
      lethal infection of Leptospira. This is the first report concerning the use of an
      anti-Id antibody against leptospirosis.

PMID- 8860970
TI  - Bioavailability and diuretic effect of furosemide following administration of
      tablets and retarded capsules to human subjects.
AB  - Two kinds of dosage forms (tablets and retarded capsules) of furosemide (F) were
      compared in vitro dissolution profile and in vivo absorption studies. The
      dissolution of F from retarded capsules was extremely restricted in the first
      fluid of the JP XII disintegration test (within 0.8%), while the dissolution of F
      from tablets and retarded capsules in the second fluid of JP XII disintegration
      test were both complete. Metabolite specific assay of F showed F, conjugation of
      F with glucuronic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or
      plasma. The mean cumulative urinary excretion of F following administration of
      the tablets during 24 h was twice that of retarded capsules. The mean area under
      the plasma concentration-time curve (AUC) of F following administration of
      tablets was 1.5 times that of retarded capsules. The mean cumulative urine volume
      during 24 h, however, was not significantly different between the two dosage
      forms. Clockwise hysteresis relationships between the diuretic response and the
      urinary excretion rate of F was observed after administration of retarded
      capsules. A straight relation between logarithm of the diuresis and logarithm of
      the urinary excretion of F was observed after maximum excretion rate of F
      following administration of both dosage forms.

PMID- 8860988
TI  - The metzincin-superfamily of zinc-peptidases.

PMID- 8860989
TI  - Structure and biosynthesis of meprins.

PMID- 8860990
TI  - Involvement of tissue inhibitors of metalloproteinases (TIMPS) during matrix
      metalloproteinase activation.

PMID- 8860991
TI  - Structure and function of a novel arginine-specific cysteine proteinase
      (argingipain) as a major periodontal pathogenic factor from porphyromonas
      gingivalis.

PMID- 8860992
TI  - Discovery of a new type of proteinase inhibitor family whose members have an
      anchoring sequence.

PMID- 8860993
TI  - Proposed role of a gamma-interferon inducible proteasome-regulator in antigen
      presentation.

PMID- 8860994
TI  - Novel members of mammalian kexin family proteases, pace 4C, pace 4D, PC 7A and PC
      7B.

PMID- 8860995
TI  - Phytocystatins and their target enzymes-molecular cloning, expression and
      possible functions.

PMID- 8860996
TI  - Horseshoe crab factor G: a new heterodimeric serine protease zymogen sensitive to
      (1 --> 3)-beta-D-glucan.

PMID- 8860997
TI  - The 43 kDa papain-inhibiting protein in psoriatic epidermis is identical to
      squamous cell carcinoma antigen (SCC-antigen).

PMID- 8860998
TI  - Alpha-mercaptoacrylic acid derivatives as novel selective calpain inhibitors.

PMID- 8860999
TI  - Structural aspects of autophagy.
AB  - As a first step towards isolation of autophagic sequestering membranes
      (phagophores), we have purified autophagosomes from rat hepatocytes. Lysosomes
      were selectively destroyed by osmotic rupture, achieved by incubation of
      hepatocyte homogenates with the cathepsin C substrate glycyl-phenylalanyl
      naphthylamide (GPN). Mitochondria and peroxisomes were removed by Nycodenz
      gradient centrifugation, and cytosol, microsomes and other organelles by rate
      sedimentation through metrizamide cushions. The purified autophagosomes were
      bordered by dual or multiple concentric membranes, suggesting that autophagic
      sequestration might be performed either by single autophagic cisternae or by
      cisternal stacks. Okadaic acid, a protein phosphatase inhibitor, disrupted the
      hepatocytic cytokeratin network and inhibited autophagy completely in intact
      hepatocytes, perhaps suggesting that autophagy might be dependent on intact
      intermediate filaments. Vinblastine and cytochalasin D, which specifically
      disrupted microtubules and microfilaments, respectively, had relatively little
      (25-30%) inhibitory effect on autophagic sequestration. In a cryo-ultrastructural
      study, the various autophagic-lysosomal vacuoles were immunogold-labelled, using
      the cytosolic enzyme superoxide dismutase as an autophagic marker, Lgp120 as a
      lysosomal membrane marker, and bovine serum albumin as an endocytic marker.
      Vinblastine (50 microM) was found to inhibit both autophagic and endocytic flux
      into the lysosomes, with a consequent reduction in lysosomal size. Asparagine (20
      mM) caused swelling of the lysosomes, probably as a result of the ammonia
      formation that could be observed at this high asparagine concentration.
      Autophagosomes and amphisomes (autophagic-endocytic, prelysosomal vacuoles)
      accumulated in asparagine-treated cells, reflecting an inhibition of autophagic
      flux that might be a consequence of lysosomal dysfunction.

PMID- 8861000
TI  - Mechanism of autophagy in permeabilized hepatocytes: evidence for regulation by
      GTP binding proteins.

PMID- 8861001
TI  - Lysosomal proteinosis based on decreased degradation of a specific protein,
      mitochondrial ATP synthase subunit C: Batten disease.

PMID- 8861002
TI  - The neuronal ceroid lipofuscinoses (Batten disease): a group of lysosomal
      proteinoses.

PMID- 8861003
TI  - Energy-dependent degradation of a mutant serine: pyruvate/alanin: glyoxylate
      aminotransferase in a primary hyperoxaluria type 1 case.

PMID- 8861004
TI  - Endopeptidase-24.11 (neprilysin) and relatives: twenty years on.

PMID- 8861005
TI  - Function of calpains: possible involvement in myoblast fusion.

PMID- 8861006
TI  - Cleavage of the human C5A receptor by proteinases derived from Porphyromonas
      gingivalis: cleavage of leukocyte C5a receptor.
AB  - The anaerobic bacteria P. gingivalis has been implicated as a primary causative
      agent in adult periodontitis. Several proteinases are produced by this bacteria
      and it is suggested that they contribute to virulence and to local tissue injury
      resulting from infection by P. gingivalis. Collagenases and cysteine proteinases
      (i.e., the gingipains) have been characterized as the predominant vesicular
      enzymes produced by this bacterium. It has been shown that an arginine-specific
      cysteine proteinase from P. gingivalis, called gingipain-1 or Arg-gingipain, can
      selectively cleave complement components C3 and C5. In the case of C5, cleavage
      by Arg-gingipain results in the generation of C5a, a potent chemotactic factor
      for PMNs. Since these bacterial proteinases are capable of generating pro
      inflammatory factors at sites of infection, we examined the possibility that
      gingipains or other proteinases from this bacterium might attack or destroy cell
      surface proteins, such as receptor molecules. Using an affinity-purified rabbit
      antibody raised against residues 9-29 of the C5a receptor (i.e., C5aR; CD88), the
      signal transmitting element for the pro-inflammatory mediator C5a, we
      demonstrated that the mixture of proteinases in P. gingivalis vesicles cleaves
      the C5a receptor on human neutrophils. This vesicular proteinase activity did not
      require cysteine activation which indicates that proteinases other than the
      gingipains may be responsible for cleavage of the C5aR molecule. in addition, the
      purified Lys-gingipain, but not Arg-gingipain, also cleaved C5aR on the human
      neutrophils. The N-terminal region of CaR (residues 9-29, PDYGHYDDKDTLDLNTPVDKT)
      was readily cleaved by chymotrypsin, but not by trypsin, despite the presence of
      potential trypsin (i.e., lysyl-X) cleavage sites. The specific sites of C5aR 9-29
      peptide cleavage were determined by mass spectroscopy for both chymotrypsin and
      Lys-gingipain. These studies suggest that the proteolytic activity in the
      bacterial vesicles that is responsible for cleaving C5aR is primarily a non
      tryptic proteinase, distance from either Arg- or Lys-gingipain. Consequently,
      there appear to be additional proteinase(s) in the vesicles that attacks the cell
      surface molecule C5aR which are not the same (i.e., Arg- and Lys-gingipain) as
      were shown to generate pro-inflammatory activity from complement components C3
      and C5. Evidence that the proteinases which attack the inflammatory precursor
      molecules (i.e., C3 and C5) exhibit different specificities than those that
      attack receptors to these bioactive complement products makes a particularly
      interesting story of how this bacteria avoids major host defense mechanisms. It
      is well known that generation of pro-inflammatory factors such as C3a and C5a at
      extra-vascular sites can promote edema, leukocyte recruitment and cellular
      activation responses that could lead to the release of toxic oxygen products and
      to phagocytosis of the bacteria. Destruction of receptors to these cellular
      activating factors generated by bacterial proteinases may eliminate the ability
      of these (i.e., complement-derived) and other mediators to carry out their anti
      bacterial actions and thereby limit the host's defense mechanisms in responses to
      the infecting bacteria. The concept of anti-bacterial responses (i.e., oxygen
      radical generation and phagocytosis) being effectively eliminated at the injury
      site, by bacterial proteinases acting at the cellular receptor level, has not
      been studied in detail. In this case, the situation is particularly unusual
      because, once the bacterial gingipains generate potent plasma-derived
      inflammatory factors that can enhance edema and deliver essential nutrients to
      the bactgeria, other bacterial proteinases may destsroy their cellular receptors.
      These receptors transmit the signal activation mechanisms in the infiltrating
      cells that elicit bacterial killing.(ABSTRACT TRUNCATED)

PMID- 8861007
TI  - Regulation of programmed cell death by interleukin-1 beta-converting enzyme
      family of proteases.

PMID- 8861008
TI  - Inhibition of cysteine and serine proteinases by the cowpox virus serpin CRMA.

PMID- 8861010
TI  - Protein and gene structures of 20S and 26S proteasomes.
AB  - The two types of proteasomes with apparent sedimentation coefficients of 20S and
      26S consist of a number of heterogeneous polypeptides and are unusually large
      protein complexes of approximately 750 kDa and 2000 kDa, respectively. The 26S
      proteasome is a cylindrical caterpillar-shaped complex with a symmetrical
      assembly of a four-layered central 20S proteasome and two terminal 22S regulators
      each with a V-like structure. The central core and the terminal structures are
      formed by multiple polypeptides with molecular masses of 21-31 kDa and 28-112
      kDa, respectively. We have been studying their detailed structures by protein
      chemical and molecular biological techniques. In this review, we summarize the
      structural features of eukaryotic 20S and 26S proteasomes. We also discuss the
      possible function(s) of the terminal multi-protein regulator complex based on
      current information.

PMID- 8861009
TI  - Participation of cathepsins B, H, and L in perikaryal condensation of CA1
      pyramidal neurons undergoing apoptosis after brief ischemia.

PMID- 8861011
TI  - The proteasome and protein degradation in yeast.

PMID- 8861012
TI  - Ubiquitin C-terminal hydrolases in chick skeletal muscle.

PMID- 8861013
TI  - Protein synthesis elongation factor EF-1 alpha is an isopeptidase essential for
      ubiquitin-dependent degradation of certain proteolytic substrates.
AB  - Targeting of different cellular proteins for conjugation and subsequent
      degradation via the ubiquitin pathway involves diverse recognition signals and
      distinct enzymatic factors. A few proteins are recognized via their N-terminal
      amino acid residue and conjugated by a ubiquitin-protein ligase that recognizes
      this residue. However, most substrates, including N-alpha-acetylated proteins
      that constitute the vast majority of cellular proteins, are targeted by different
      signals and are recognized by yet unknown ligases. In addition to the ligases,
      other factors may also be specific for the recognition of this subset of
      proteins. We have previously shown that degradation of N-terminally blocked
      proteins require a specific factor, designated FH, and that the factor acts along
      with the 26S protease complex to degrade ubiquitin-conjugated proteins (Gonen et
      al., 1991). Further studies have shown that FH is identical to the protein
      synthesis elongation factor EF-1 alpha, and that it can be substituted by the
      bacterial elongation factor EF-Tu (Gonen et al., 1994). This, rather surprising,
      finding raises two important and interesting problems. The first involves the
      mechanism of action of the factor and the second the possibility that protein
      synthesis and degradation may be regulated by a commonly shared factor. Here, we
      demonstrate that EF-1 alpha is a ubiquitin C-terminal hydrolase (isopeptidase)
      that is probably involved in trimming the conjugates to lower molecular weight
      forms recognized by the 26S proteasome complex. Additional findings demonstrate
      that its activity is inhibited specifically by tRNA. This finding raises the
      possibility that under anabolic conditions, when the factor is associated with
      AA.tRNA and GTP, it is active in protein synthesis but inactive in proteolysis.
      Under catabolic conditions, when the factor is predominantly found in its apo
      form, it is active in proteolysis.

PMID- 8861014
TI  - Mechanisms and regulation of ubiquitin-mediated cyclin degradation.

PMID- 8861015
TI  - Physiological functions of proteasomes in ascidian fertilization and embryonic
      cell cycle.

PMID- 8861016
TI  - Cellular proteases involved in the pathogenicity of human immunodeficiency and
      influenza viruses.

PMID- 8861017
TI  - HIV protease mutations leading to reduced inhibitor susceptibility.

PMID- 8861018
TI  - Aspartic proteinases from parasites.

PMID- 8861019
TI  - Tetanus and botulism neurotoxins: a novel group of zinc-endopeptidases.
AB  - Tetanus and botulinum neurotoxins are produced by bacteria of the genus
      Clostridium and cause the paralytic syndromes of tetanus and botulism with a
      persistent inhibition of neurotransmitter release at central and peripheral
      synapses, respectively. These neurotoxins consist of two disulfide-linked
      polypeptides: H (100 kDa) is responsible for neurospecific binding and cell
      penetration of L(50 kDa), a zinc-endopeptidase specific for three protein
      subunits of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum
      neurotoxins serotypes B, D, F, and G cleave at single sites, which differ for
      each neurotoxin. VAMP/synaptobrevin, a membrane protein of the synaptic vesicles.
      Botulinum A and E neurotoxins cleave SNAP-25, a protein of the presynaptic
      membrane, at two different carboxyl-terminal peptide bonds. Serotype C cleaves
      specifically syntaxin, another protein of the nerve plasmalemma. The target
      specificity of these metallo-proteinases relies on a double recognition of their
      substrates based on interactions with the cleavage site and with a non contiguous
      segment that contains a structural motif common to VAMP, SNAP-25 and syntaxin.

PMID- 8861020
TI  - Endosome-lysosomes, ubiquitin and neurodegeneration.
AB  - Before the advent of ubiquitin immunochemistry and immunogold electron
      microscopy, there was no known intracellular molecular commonality between
      neurodegenerative diseases. The application of antibodies which primarily detect
      ubiquitin protein conjugates has shown that all of the human and animal
      idiopathic and transmissible chronic neurodegenerative diseases, (including
      Alzheimer's disease (AD), Lewy body disease (LBD), amyotrophic lateral sclerosis
      (ALS), Creutzfeldt-Jakob disease (CJD) and scrapie) are related by some form of
      intraneuronal inclusion which contains ubiquitin protein conjugates. In addition,
      disorders such as Alzheimer's disease, CJD and sheep scrapie, are characterised
      by deposits of amyloid, arising through incomplete breakdown of membrane proteins
      which may be associated with cytoskeletal reorganisation. Although our knowledge
      about these diseases is increasing, they remain largely untreatable. Recently,
      attention has focused on the mechanisms of production of different types of
      amyloid and the likely involvement within cells of the endosome-lysosome system,
      organelles which are immuno-positive for ubiquitin protein conjugates. These
      organelles may be 'bioreactor' sites for the unfolding and partial degradation of
      membrane proteins to generate the amyloid materials or their precursors which
      subsequently become expelled from the cell, or are released from dead cells, and
      accumulate as pathological entities. Such common features of the disease
      processes give new direction to therapeutic intervention.

PMID- 8861021
TI  - Abnormalities of the endosomal-lysosomal system in Alzheimer's disease:
      relationship to disease pathogenesis.

PMID- 8861022
TI  - Cathepsin B expression in human tumors.
AB  - Cathepsin B has been linked to tumor progression through observations that its
      activity, secretion or membrane association are increased. The most malignant
      tumors, and specifically the cells at the invasive edge of those tumors, express
      the highest activity. Cathepsin B may facilitate invasion directly by dissolving
      extracellular matrix barriers like the basement membrane, or indirectly by
      activating other proteases capable of digesting the extracellular matrix.
      Cathepsin B also might play a role in tumor growth and angiogenesis. Cathepsin B
      activity is the result of several levels of regulation: transcription, post
      transcription processing, translation and glycosylation, maturation and
      trafficking, and inhibition. The majority of reports on cathepsin B expression in
      tumors have focused on measurements of activity or protein staining. In some
      tumors, e.g. gliomas, a correlation between the amounts of cathepsin B mRNA,
      protein and activity and tumor progression has been established. Regulation of
      cathepsin B at the transcriptional and post-transcriptional levels is still
      poorly understood. Although the putative promoter regions have characteristics of
      housekeeping-type promoters, cathepsin B mRNA expression varies depending on the
      cell type and state of differentiation. We have evidence that more than one
      promoter could direct expression of human cathepsin B. Multiple transcript
      species have been detected, resulting from alternative splicing in the 5'- or 3'
      untranslated regions, and possibly the use of alternative promoter regions. The
      existence of transcript variants indicates a potential for post-transcriptional
      control of expression. In support of this, ras-transformation of MCF-10A human
      breast epithelial cells results in an increase in protein levels without a
      concomitant increase in mRNA levels. Cathepsin B mRNA species with distinct 5'-
      or 3'-untranslated regions may differ in their stability and translatability.
      Variations in the coding region may also alter cathepsin B properties. We and
      Frankfater's group have observed transcript species that would encode a truncated
      protein, lacking the prepeptide and about half of the propeptide. This truncated
      protein, if synthesized in cells, would be expected to be cytosolic; therefore
      its function is unclear. Once the several mechanisms of regulation of cathepsin B
      expression and activity are better understood, they could provide us with new
      strategies to specifically reduce cathepsin B activity in tumors.

PMID- 8861023
TI  - TIMP-2 mediates cell surface binding of MMP-2.
AB  - In order to understand the mechanism for neoplastic cell invasion, we utilized
      binding studies of TIMP-2, gelatinase A and the TIMP-2/gelatinase A complex to
      neoplastic cells and correlated these results with their capacity to invade a
      matrix substrate in a modified Boyden chamber assay. Binding studies were
      performed on malignant human breast cancer cells and fibrosarcoma cells with
      rTIMP-2, rGelatinase A, and TIMP-2/gelatinase A complex. Competition studies of
      the binding characteristics of these proteins indicated that gelatinase A and
      gelatinase A/TIMP-2 complex bound to the surface of cells via TIMP-2.
      Furthermore, the localization of either latent or active protease to the surface
      of MDA-MB-435 breast cancer cells facilitated the invasion of these neoplastic
      cells through a matrigel barrier. This suggests that in addition to binding this
      complex, these cells can activate this pro-enzyme-inhibitor complex and use this
      activity to facilitate cellular invasion. Moreover, their enhanced invasion was
      suppressed by exogenous additions of rTIMP-2. A working hypothesis and model for
      the role of gelatinase A/TIMP-2 complex in cellular invasion is presented.

PMID- 8861024
TI  - The 1st International Conference on Tularemia. Umea, Sweden, 23-25 August 1995.
      Proceedings.

PMID- 8861025
TI  - Francisella tularensis: host-parasite interaction.

PMID- 8861026
TI  - Epidemiological analysis of tularemia in Japan (yato-byo).
AB  - A total of 1372 cases of tularemia observed in Japan since 1924 were analysed.
      More than 90% of the cases were reported in the north-eastern part of the main
      island of Japan. After World War II, more than 40 cases were reported yearly for
      20 years. Since 1966, however, there have been less than 10 cases per year.
      Ninety-three % of the cases were caused by contact with infected wild rabbits.
      The pattern of monthly distribution showed a peak in December and also a lower
      peak in May. The number of patients older than 40 years of age and the proportion
      of cases in females have gradually increased. In the earlier survey periods
      almost 70% of the cases were engaged in agriculture but at present this rate is
      less than 50%. The changes in the occurrence of tularemia in Japan is thought to
      be related to the change of life style caused by the rapid growth of the Japanese
      economy after World War II.

PMID- 8861027
TI  - Field investigations of tularemia in Norway.
AB  - In Norway, tularemia is a common disease in small rodent and hare populations,
      where large outbreaks can be observed. In humans, the yearly number of cases is
      low, usually less than ten, with peaks up to 44 recorded in recent years.
      Serological investigations on hunters and healthy school children nevertheless
      indicate, with up to 4.7% positivity in the latter group, that Francisella
      tularensis low-grade infection is widespread. F. tularensis in co-culture with
      amoebae, e.g. Achantamoeba castellanii, may grow after internalization and kill
      the amoeba. As with Legionella, Francisella virulence may be enhanced after
      protozoan ingestion. This suggests a mechanism that can explain the pattern of
      dissemination and infection in our region.

PMID- 8861028
TI  - Tularemia: association with hunting and farming.

PMID- 8861029
TI  - Epidemiological analysis of tularemia in Sweden 1931-1993.

PMID- 8861030
TI  - Immunogenicity of a new lot of Francisella tularensis live vaccine strain in
      human volunteers.
AB  - A new lot of Francisella tularensis live vaccine strain (LVS) was tested for
      immunogenicity in 19 human volunteers. Scarification vaccination induced specific
      cell-mediated and humoral immune responses. We noted a significant rise in
      antibodies against irradiation-killed LVS, formalin-killed virulent strain SCHU4,
      and an ether extracted antigen preparation (EEx) beginning 14 days after
      vaccination. A main target of the humoral immune response was lipopolysaccharide.
      Eighty percent of vaccinated volunteers developed a positive IgG response to EEx
      by day 14 and 100% of vaccinees responded positively by day 21. Background IgA
      titers were lower than corresponding IgG or IgM titers. No early IgM rise was
      noted with any antigen. By day 14 after vaccination, in vitro lymphocyte
      responses to LVS, the rough variant of LVS, and EEx were significantly increased
      compared to controls. Seventy percent of volunteers had a positive in vitro
      lymphocyte response to EEx within 14 days of vaccination. We predict that EEx
      will be a useful antigen for diagnosing tularemia and for evaluating the
      immunogenicity of vaccines against tularemia. We are testing this antigen using
      sera from human cases of tularemia and control sera.

PMID- 8861032
TI  - The new vaccine strains (or variants) of Francisella tularensis.
AB  - A colony (N83) of the vaccine strain of Francisella tularensis (15/10) and a
      strain (N268) isolated from a water sample in nature were revealed for
      susceptibility to cultivation at 42 degrees C. Both strains had low virulence for
      white mice and were avirulent for guinea pigs but possessed high immunogenicity
      in these animals. The spontaneous mutant of vaccine strain 15/10 showed
      resistance to doxicycline and rifampicine (15/10 Dox (r)40 Rif (r)40). The
      obtained mutant had biological characteristics similar to the parent vaccine
      strain. It provided immunity in experimental animals when vaccination and
      antimicrobial agents were used in combination.

PMID- 8861031
TI  - Live tularemia vaccine confers protection against lethal Legionella and Listeria
      infections in experimental animals.
AB  - The efficacy of a live Francisella tularensis vaccine strain to cause nonspecific
      immunity toward experimental legionellosis and listeriosis was studied.
      Immunisation with tularemia vaccine protected over 80% and 17% of experimental
      animals against subsequent lethal challenge with Legionella pneumophila and
      Listeria monocytogenes, respectively. The protection was maximal during the first
      month following immunisation and declined thereafter. In order to delineate the
      immunostimulatory moieties of the Francisella microbe, several cell wall proteins
      have been purified and characterized. However, isolated cell wall components
      failed to induce protection.

PMID- 8861033
TI  - Orchestration of the protective immune response to intracellular bacteria:
      Francisella tularensis as a model organism.
AB  - Francisella tularensis is used as a model organism in studies of mechanisms
      behind the induction of a protective T-cell response in the mammalian host.
      Protective immunity is associated with a CD4 and CD8 T-cell response towards a
      mosaic of proteins of F. tularensis and due to HLA restriction, each individual
      selects her own mosaic. No single protein has so far been shown to be
      immunodominant. Only live F. tularensis affords effective host protection.
      Subcellular antigen preparations induce only a marginal protective response even
      when combined with potent adjuvants such as immunostimulating complexes (ISCOMs).
      In mice, intradermal injection of live F. tularensis but not of killed bacteria
      results in an early cytokine expression in the infected liver, including
      interleukin-12, tumor necrosis factor-alpha, and interferon-gamma. This cytokine
      response seems to be a prerequisite for effective priming of T cells to an array
      of proteins of F. tularensis to occur.

PMID- 8861034
TI  - Outer membranes of a lipopolysaccharide-protein complex (LPS-17 kDa protein) as
      chemical tularemia vaccines.
AB  - Immunisation with outer membranes of Francisella tularensis induced an efficient
      protection in guinea pigs against challenge with the virulent strains 503 or
      144/713 (type B biovar holarctica), both clinical isolates, and prevented the
      development of typical signs of infection in hamadryads (baboons), challenged
      with the virulent strain Schu (type A, biovar tularensis) of F. tularensis.
      Immunisation with a lipopolysaccharide protein complex isolated from the outer
      membranes afforded protection in CBA mice against challenge with strain 503.
      Another LPS-protein complex obtained by the simple mixture of LPS preparations
      from strain 503 and a 17-kDa membrane protein from the avirulent R-variant of the
      vaccine strain 15 also demonstrated protective properties against experimental
      tularemia in mice.

PMID- 8861035
TI  - The immune response against Francisella tularensis live vaccine strain in Lps(n)
      and Lps(d) mice.
AB  - The impact of Lps gene on the course of immune response against subcutaneous
      infection of mice with Francisella tularensis live vaccine strain was studied.
      Production and specificity of antibodies, cytotoxic responses of macrophages and
      NK-cells, spontaneous production ex vivo of cytokines IL-1 alpha, IL-2, IL-4, IL
      6, IL-10, IFN-gamma, and TNF-alpha in spleen cell cultures in C3H/HeJ (Lps(d))
      mice in comparison with C3H/HeN (Lps(n)) mice were tested. The value of LD(50)
      was significantly different in the two strains of mice (8.0 x 10(5) cfu for
      C3H/HeJ versus 4.61 x 10(3) cfu for C3H/HeJ mice after subcutaneous inoculation).
      The production of NO(2) is also impaired in C3H/HeJ mice in the early intervals
      after infection. Thus, the defective Lps gene of C3H/HeJ mice influences both the
      level of innate resistance of mice to F. tularensis live vaccine strain infection
      and the process of induction and regulation of immune response against this
      intracellular bacterial pathogen.

PMID- 8861036
TI  - Cytokine expression in the liver of mice infected with a highly virulent strain
      of Francisella tularensis.
AB  - Cytokine mRNA expression was determined in the liver of mice subcutaneously
      inoculated with a lethal dose of the highly virulent strain FSC 041 of
      Francisella tularensis subvar, tularensis or a sublethal dose of the live vaccine
      strain of F. tularensis subvar. palaearctica. Expression of mRNA for TNF-alpha,
      IL-12, IFN-gamma, and IL-10 was demonstrated within 48 h of inoculation, the
      kinetics being similar irrespective of bacterial strain used. Thus, the
      expression of a cytokine response believed to be important in the early host
      defence against live vaccine strain seemed insufficient to prevent the lethality
      of a more virulent strain.

PMID- 8861037
TI  - Role of two outer membrane antigens in the induction of protective immunity
      against Francisella tularensis strains of different virulence.
AB  - A crude outer membrane preparation from Francisella tularensis live vaccine
      strain was used to immunise mice. Immunised mice were completely protected from a
      F. tularensis challenge. We evaluated the role of two major outer membrane
      antigens in the induction of protective immunity, namely lipopolysaccharide and
      an outer membrane protein FopA. We presented FopA to the immune system using an
      aromatic amino acid dependent Salmonella typhimurium as a vector. Although mice
      mounted an immune response to cloned FopA no significant protection was induced.
      However, lipopolysaccharide-immunised mice were completely protected from a
      F.tularensis live vaccine strain challenge. No increase in LD50 was observed
      using F. tularensis Schu4 as the challenge strain, although there was a
      significant increase in time to death. These data question the validity of the
      murine F. tularensis live vaccine strain model.

PMID- 8861038
TI  - Francisella tularensis resistance to bactericidal action of normal human serum.
AB  - Lipopolysaccharide and outer membranes from the three virulent encapsulated
      (Cap(+)) strains of three subspecies of Francisella tularensis and their isogenic
      avirulent capsule-deficient (Cap(-)) mutants were isolated. It was shown that the
      Cap cells and their outer membranes almost completely consumed the available
      complement of normal human serum whereas Cap(-) LPS (R-LPS), Cap(+) cells and
      their components activated the complement less effectively. Absorption of normal
      human serum with Cap(-) strain dramatically reduced the complement consumption
      for homologous strain and its surface structures. This reduction reflected the
      loss of bactericidal antibodies. Addition of antibodies to whole cells of F.
      tularensis completely restored complement activity. The cross-absorbing
      experiments demonstrated that Cap(-) cells more effectively deplete bactericidal
      antibodies than homologous virulent strain. From these results it can be
      concluded that normal human serum is bactericidal for serum-sensitive Cap(-) F.
      tularensis strains through the action of complement initiated by the classical
      complement pathway and serum resistance of virulent strains is not due to absence
      of targets for bactericidal antibodies, but is due to their low accessibility
      because of O-side chains of lipopolysaccharide.

PMID- 8861039
TI  - Cryptic plasmid pFNL10 from Francisella novicida-like F6168: the base of plasmid
      vectors for Francisella tularensis.
AB  - The plasmid pFNL1OO was created by ligation of Escherichia coli plasmid pBR328
      and plasmid pFNL1O from Francisella novicida-like strain F6168. This plasmid was
      able to replicate and to express the genes for chloramphenicol and tetracycline
      resistance in both E. coli and F. tularensis. The origin of replication of
      pFNL1O, needed for the replication of pFNL1OO in F. tularensis, was mapped. A
      Sau3A-deletion derivative of pFNL1OO, designated pFNL2OO, was constructed. This
      plasmid could replicate only in F. tularensis and was found to be stably
      inherited during cultivation both on solid medium and in liquid cultures.

PMID- 8861040
TI  - Construction of a shuttle vector for use in Francisella tularensis.
AB  - The characterisation of virulence factors of Francisella tularensis has been
      hampered by the lack of genetic system for the bacterium. In this study, a
      shuttle vector was constructed that can replicate autonomously in F. tularensis
      and Escherichia coli. To obtain this vector, the p15A replication origin of F.
      coli plasmid pACYC184 was introduced into a plasmid derivative of plasmid
      pFNL2OO, a plasmid which only can replicate in F. tularensis. The resulting
      shuttle vector, designated pKK2O2, harboured resistance genes for chloramphenicol
      and tetracycline. This vector might be used as a basis for the studies of
      virulence factors of F. tularensis.

PMID- 8861041
TI  - What is case-finding?

PMID- 8861042
TI  - Should testicular self examination be recommended?

PMID- 8861043
TI  - Testicular cancer: to screen or not to screen?
AB  - OBJECTIVES - To evaluate the evidence for and against routine testicular cancer
      screening by primary health care providers and patients (testicular self
      examination). SETTING - Low reported frequency of routine screening for
      testicular cancer attributed to poor knowledge of the disease and how to screen
      for it. METHODS - Literature based evaluation of the screening suitability of
      testicular cancer as a disease and palpation of the testis as the proposed
      screening test, and of the effectiveness of screening for testicular cancer.
      RESULTS - Testicular cancer is not a major public health problem. Its low
      prevalence makes routine screening cost ineffective. As a screening test for the
      disease, palpation has high sensitivity but its levels of specificity and
      positive predictive value are unacceptable. Palpation of the testes has not been
      shown to reduce mortality or morbidity. CONCLUSION - There is insufficient
      evidence to justify routine screening for testicular cancer by health care
      providers and patients. This lack of evidence may better explain the low reported
      levels of screening than can ignorance of the evidence available.

PMID- 8861044
TI  - Early mortality and morbidity in children with Down's syndrome diagnosed in two
      regional health authorities in 1989.
AB  - OBJECTIVES - To assess the risk of early mortality and the quality of health of a
      recent cohort of 5 year old children with Down's syndrome to provide current
      information on prognosis. SETTING - A follow up study in 1994 of all live births
      with a cytogenetic diagnosis of trisomy 21 or related karyotype born in 1989 and
      diagnosed in the South East Thames and Oxford Regional Health Authorities; these
      amounted to 100 children. RESULTS - Eighteen of the sample of 100 had died in the
      first three years, and seven were reported as adopted. Fifty six mothers were
      interviewed, including five of children who had died. High rates of associated
      congenital defects were reported. The most common were congenital heart defects,
      which were reported for 29 of the 69 children for whom health information was
      available, and were certified as the underlying cause of death of 12 and required
      surgery in 11. At least five children had had gastrointestinal atresia or other
      gut blockage, most presenting at birth but one case occurring at 3 years, and
      these had necessitated a colostomy in two cases. Leukaemia had occurred in two
      children, both of whom had died. As expected mothers also reported high rates of
      defects of hearing, often treated with grommets; of vision; and frequent severe
      infections. CONCLUSIONS - Information of this nature, as well as that regarding
      the more positive aspects of Down's syndrome, should be made available to those
      counselling parents considering the offer of diagnostic tests.

PMID- 8861045
TI  - Can reliable Down's syndrome detection rates be determined from prenatal
      screening intervention trials?
AB  - OBJECTIVES - To develop a standardised approach for analysing Down's syndrome
      screening performance in clinical practice and to apply it to published
      intervention trials in order to estimate detection and false positive rates more
      accurately. METHODS - Peer reviewed intervention trials, grouped by specific
      combination of analytes, were reanalysed. Revised detection rates were calculated
      for each study, taking into account both the high spontaneous loss during the
      last half of pregnancy and the possible under ascertainment of Down's syndrome
      live births not detected by screening. Collective screening performance was
      estimated, when possible, using a published methodology based on fitting receiver
      operator characteristic curves. RESULTS - Sixteen trials were analysed; 11 using
      three, and five using two, analytes. Collective screening performance for the
      triple analyte trials was Down's syndrome detection rates of 57, 64, and 69% at
      amniocentesis referral rates of 3, 5, and 7% respectively. Four of the five
      studies involving two analytes performed less well, individually, when compared
      with the overall performance of the three analyte studies. It was not possible to
      estimate collective performance for the two analyte studies because there were
      too few. CONCLUSIONS - Accurate Down's syndrome detection rates are difficult to
      obtain in intervention trials owing to two potential biases, both of which tend
      to produce overestimates of the true rates. These sources of bias need to be
      taken into account when analysing and reporting Down's syndrome intervention
      trials. The methodology presented here offers the opportunity to achieve a more
      reliable, standardised estimate of both individual and collective intervention
      trial screening performance.

PMID- 8861046
TI  - Comparison of radiographer/radiologist double film reading with single reading in
      breast cancer screening.
AB  - OBJECTIVES - To assess the efficacy of dual film reading in screening mammography
      with a suitably trained radiographer as the second reader and to determine a
      suitable decision model for radiographer/radiologist double reading. SETTING -
      Three breast screening centres in South Thames (West) region. METHODS - Seven
      radiographers with prior film reading training double read 17 202 screening
      mammograms with a radiologist. Screening performance of radiographers and
      radiologists was assessed taking into account interval cancers. The efficacy of
      radiographer/radiologist double reading was assessed in terms of changes in
      sensitivity and specificity compared with radiologist single reading. RESULTS -
      Radiographers yielded equivalent sensitivity but lower specificity than
      radiologist film readers. The effect of double reading between
      radiographer/radiologist pairs was an increase in sensitivity of 6-4%, which was
      achieved at the cost of a 0-6% decrease in specificity. This was reached by a
      decision system involving radiologists' review of radiographer queries and recall
      classifications. If all radiographer queries were recalled a large increase in
      sensitivity would be counterbalanced by an equally large decrease in specificity.
      CONCLUSIONS - Radiographer/radiologist double reading resulted in similar
      increases in sensitivity as those previously reported in radiologist double
      reading studies. Radiologist review of radiographer reported abnormalities is a
      suitable means by which to limit excess recall.

PMID- 8861047
TI  - Invasive cervical cancer in Southampton and South West Hampshire: effect of
      introducing a comprehensive screening programme.
AB  - A study of invasive cervical cancer in Southampton and South West Hampshire is
      reported, covering three consecutive three year periods during which the
      screening coverage increased from an estimated 60% to a recorded 87% of eligible
      women aged 20-64. From the first to the third periods of the study in that age
      group registrations of fully invasive squamous cell carcinoma (stage lb and
      above) fell from 64 to 30 (53%), which was largely counteracted by an increase in
      microinvasive squamous cell carcinoma (linear trend: P<0.0001). In the same age
      group registrations of adenocarcinoma rose slightly, which resulted from an
      increase in the number diagnosed at a depth of invasion of less than 3 mm. There
      were no significant changes in the numbers of stage III and IV cancers or among
      cancers in women aged 65 and over. A strong inverse association was found between
      stage of both histological types of cancer and their likelihood of being screen
      detected rather than symptomatic: 91% of screen detected cancers were diagnosed
      at stage I compared with 38% of symptomatic cancers. There was a slight downward
      trend in the incidence of cancer per 100,000 total female population across the
      three periods of the study with a significant trend towards low stage disease,
      which is likely to reduce mortality in years to come. The trend towards screen
      detected cancers and cancers of less than 3 mm depth of invasion is presented as
      a positive outcome to be expected in early rounds of increasing the screening
      coverage.

PMID- 8861048
TI  - Consequences of current patterns of Pap smear and colposcopy use.
AB  - OBJECTIVES - To describe age specific frequencies of Pap smear and colposcopy use
      in the Australian Capital Territory (ACT) and to estimate the cumulative effects
      of current patterns of use. SETTING - Frequencies of Pap smear and colposcopy use
      were estimated for the financial year from 1 July 1989 to 30 June 1990. Eligible
      women were between the ages of 15 and 74, living in the ACT. METHODS - Data
      collected from a 10% sample of subjects enrolled with Medicare and from the only
      public pathology laboratory in the ACT were used to estimate age specific
      frequencies. The expected number of deaths from cervical cancer in the ACT in the
      absence of a screening programme was estimated by applying Australian age
      specific mortality rates for cervical cancer between 1960 and 1964 to the 1989
      ACT population. A life table approach was used to simulate the cumulative risk of
      colposcopy - given current age specific rates - on a hypothetical cohort of 1000,
      15 year old women. RESULTS - Forty four per cent (95% confidence interval (CI)
      42.9 to 44.9) of women had a Pap smear and 2.5% had colposcopy (95% CI 2.4 to
      2.6). Two and a half percent of 15 to 24 year old women had colposcopy (95% CI
      1.9 to 3.1). The ratio of women having Pap smears to women having colposcopy was
      17-8:1 (95% CI 17.7 to 17.9). An estimated 247 women had colposcopy for every
      cervical cancer death; in the 15 to 24 year old age group this ratio was 47900:1.
      A 15 year old woman exposed to current rates of colposcopy (adjusted for
      hysterectomy) has a 76.8% chance of having a colposcopy during her life time.
      CONCLUSIONS - Many more women will have colposcopy than will develop cervical
      cancer, which undermines the cost effectiveness of Australia's cervical cancer
      screening programme.

PMID- 8861049
TI  - Uptake of cervical screening in general practice: effect of practice
      organisation, structure, and deprivation.
AB  - OBJECTIVES - To investigate associations between uptake for cervical screening in
      general practice and the organisation of screening, features of practice
      structure, and deprivation. SETTING - Greater Glasgow Health Board area in the
      west of Scotland, which covers a socioeconomically varied population. METHODS -
      General practice questionnaire survey and interview based study. The main outcome
      measure was the uptake rate for each participating practice over the five and a
      half years ending 31 December 1993. This was used to determine whether practices
      achieved 80% uptake to trigger maximum payment for cervical screening services.
      RESULTS - Forty seven percent (n = 92) of all practices in the Greater Glasgow
      Health Board area agreed to take part in the research, with complete data
      collected for 87 practices. Participation varied according to number of partners
      in the practice and the average deprivation score of the practice. Uptake rates
      ranged from 48-2% to 92-9% (median 77.5%, interquartile range 69.8% to 83.4%).
      Thirty seven practices (43%) achieved the 80% target. None of the recommended
      features of good organisation of cervical screening showed any statistically
      significant association with uptake rates. In stepwise multiple regression four
      variables were shown to have independent associations with uptake. These were the
      number of partners in the practice, the average deprivation of the practice, the
      presence of a female general practitioner, and using a practice's own lists for
      sending out letters of invitation. In stepwise logistic regression just two of
      these variables contributed to the prediction of achieving 80% uptake namely,
      average deprivation and number of partners. There were no significant
      interactions between deprivation and the organisation of screening in relation to
      uptake. CONCLUSIONS - Organising cervical screening in general practice according
      to accepted standards is less important in predicting uptake than more
      intractable features of the practice such as the size of the partnership, its
      average deprivation level, the presence of a female general practitioner, and
      using their own (presumed more accurate) register of addresses to call women. A
      flexible incentive scheme may more fairly reward the efforts of those general
      practitioners who achieve high uptake rates but who do not trigger remuneration
      at the 80% level.

PMID- 8861050
TI  - CA 125 as a screening test for ovarian cancer.
AB  - BACKGROUND - Screening for ovarian cancer is based on ultrasound, colour Doppler,
      and tumour markers. There is only limited evidence on their discriminatory
      performance and no evidence on their effectiveness in reducing mortality.
      OBJECTIVE - To investigate the discriminatory performance of CA 125 as a
      screening test for ovarian cancer. METHODS - A registry of 15 093 serum samples
      drawn in 1968-72 was linked to the cancer registry. During follow up between 1968
      and 1980 24 ovarian cancers were identified. One or two matched case-control
      design nested within the sample bank was applied and the concentrations of CA 125
      were assessed. RESULTS - Case-control differences (relative risk 4-0, 95%
      confidence interval 1.0 to 15.5 at 20 kU/1) were found. Detection rate of the CA
      125 test was 21-33% and the true negative rate was 75-98% depending on the cut
      off level and interval between drawing of the blood sample and diagnosis of the
      cancer. CONCLUSION - CA 125 is not a valid screening test if used alone. Case
      control differences of borderline significance were found in CA 125 before
      diagnosis of ovarian cancer, but they were not large enough to provide a
      sufficient detection rate.

PMID- 8861051
TI  - Hospital based screening of 65-73 year old men for abdominal aortic aneurysms in
      the county of Viborg, Denmark.
AB  - OBJECTIVE - To analyse the benefits of screening older men for abdominal aortic
      aneurysms. METHODS - A hospital based screening trial concerning 13 500 65-73
      year old men using B-mode ultrasonographic scanning. To improve the response rate
      the invited men could change their appointment, and nonresponders were reinvited.
      RESULTS - Results from the first year of the trial are presented. Among 4404
      invited, 3344 (76%) were scanned. The primary response rate was 64.8%, but a
      further 11.2% were scanned after revised appointments or reinvitation. The whole
      infrarenal aorta could be visualised in 97-6%, and the distal part in 99.7% of
      the scans. The time taken for each scan was 9-7 minutes and the costs per scan
      were $9.50. One hundred and fifty three subjects (4.6%) had aortic diameters of
      25-29 min, and 141 (4.2%) had an abdominal aortic aneurysm, 19 (0.6%) above 49 mm
      in diameter. CONCLUSION - In Denmark the short term costs and benefits of
      screening older men for abdominal aortic aneurysms seem realistic. Long term
      costs and benefits need to be investigated.

PMID- 8861052
TI  - Screening for melanoma by primary health care physicians: a cost-effectiveness
      analysis.
AB  - BACKGROUND AND DESIGN - Australia has the highest rates of skin cancer in the
      world, and the incidence is estimated to be doubling every 10 years. Despite
      advances in the early detection and treatment of melanoma about 800 people still
      die nationally of the disease each year. A possible strategy for further reducing
      the mortality from melanoma is an organised programme of population screening for
      unsuspected lesions in asymptomatic people. Arguments against introducing
      melanoma screening have been based on cost and the lack of reliable data on the
      efficacy of any screening tests. To date, however, there has been no systematic
      economic assessment of the cost effectiveness of melanoma screening. The purpose
      of this research was to determine whether screening may be potentially cost
      effective and, therefore, warrants further investigation. A computer was used to
      simulate the effects of a hypothetical melanoma screening programme that was in
      operation for 20 years, using cohorts of Australians aged 50 at the start of the
      programme. Based on this simulation, cost-effectiveness estimates of melanoma
      screening were calculated. RESULTS - Under the standard assumptions used in the
      model, and setting the sensitivity of the screening test (visual inspection of
      the skin) at 60%, cost effectiveness ranged from Aust$6853 per life year saved
      for men if screening was undertaken five yearly to $12 137 if screening was two
      yearly. For women, it ranged from $11 102 for five yearly screening to $20 877
      for two yearly screening. CONCLUSION - The analysis suggests that a melanoma
      screening programme could be cost effective, particularly if five yearly
      screening is implemented by family practitioners for men over the age of 50.

PMID- 8861054
TI  - Methamphetamines pretreatment and the vulnerability of the striatum to
      methamphetamine neurotoxicity.
AB  - Pretreatment with intermittent low-dose administrations of stimulants increases
      mesostriatal dopamine transmission upon administration of a challenge dose. This
      occurs without evidence of a long-term dopamine or serotonin depletion. The
      purpose was to examine whether pretreatment with low doses of methamphetamine
      enhances dopamine and/or glutamate efflux and the subsequent depletion of
      dopamine and serotonin produced by neurotoxic challenge doses of methamphetamine.
      Microdialysis was used to measure simultaneously extracellular concentrations of
      dopamine and glutamate in the striatum and prefrontal cortex of awake rats. Basal
      extracellular concentrations of dopamine and glutamate were unaltered following
      pretreatment with methamphetamine. The increase in methamphetamine-induced
      striatal dopamine efflux was not significantly different between methamphetamine
      and saline pretreated groups. In contrast, after high challenge doses of
      methamphetamine, dopamine efflux in prefrontal cortex was enhanced to a greater
      extent in methamphetamine pretreated rats as compared to saline pretreated
      controls. Acute methamphetamine did not enhance glutamate efflux in prefrontal
      cortex after pretreatment with saline or methamphetamine. The increase in
      striatal glutamate efflux was blunted in rats pretreated with methamphetamine.
      When measured 4 days later, dopamine and serotonin content in striatum was
      depleted in all rats acutely challenged with methamphetamine. However, these
      depletions were attenuated in rats pretreated with methamphetamine. An acute
      methamphetamine challenge did not affect dopamine tissue content in the
      prefrontal cortex of any rats. Serotonin content in cortex was depleted in all
      groups following the methamphetamine challenge administration, but these
      depletions were diminished in methamphetamine-pretreated rats. These results are
      the first evidence that an intermittent pretreatment regimen with low doses of
      methamphetamine, followed by a 1 week withdrawal, reduces the vulnerability of
      striatal dopamine and serotonin terminals and cortical serotonin terminals to
      methamphetamine neurotoxicity. These findings provide evidence for the mechanism
      leading to methamphetamine neurotoxicity.

PMID- 8861055
TI  - Scopolamine augments c-fos and zip/268 messenger RNA expression induced by the
      full D(1) dopamine receptor agonist SKF-82958 in the intact rat striatum.
AB  - It is generally accepted that the widely used, partial dopamine D(1) receptor
      agonist, SKF-38393, does not induce immediate early gene expression in striatal
      projection neurons unless D(1) receptors are sensitized and uncoupled from D(2)
      receptors by 6-hydroxydopamine lesions or reserpine treatment. In contrast, this
      study demonstrates, using quantitative in situ hybridization, that the full D(1)
      receptor agonist, SKF-82958, induced robust expression of c-fos and zif/268
      messenger RNAs in the intact rat striatum, especially in the entire shell and
      medial and ventral core areas of the nucleus accumbens and olfactory tubercle,
      and in the cerebral cortex, 45 min after one injection. The induction of the
      striatal immediate early genes is characterized by (i) induction in only medium
      sized spiny neurons, (ii) dose-dependent induction, which correlates well with
      dose-dependent increases in motor activity, and (iii) blockade by the D(1)
      receptor antagonist, SCH-23390. The muscarinic cholinergic receptor antagonist,
      scopolamine, which itself did not alter striatal gene expression, profoundly
      augmented the behaviors and expression of the two immediate early genes in the
      ventral and dorsal striatum induced by 0.1, 0.5 and 2.0 mg/kg SKF-82958. However,
      scopolamine attenuated basal, and SKF-82958-stimulated, expression of c-fos and
      zif/268 messenger RNAs in the cortex. Scopolamine also enabled SKF-38393 to
      induce locomotor stimulation and c-fos and zif/268 messenger RNA expression in
      the normosensitive striatum of the rat when SKF-38393 alone caused no such
      changes. These data demonstrate an ability of SKF-82958 to induce immediate early
      gene messenger RNA expression in normosensitive dorsal and ventral striatum.
      Furthermore, intrinsic muscarinic receptor-mediated cholinergic transmission in
      the striatum may provide an activity-dependent inhibitory control on striatal
      D(1) receptor stimulation.

PMID- 8861056
TI  - Models of ganglion cell topography in the retina of macaque monkeys and their
      application to sensory cortical scaling.
AB  - We devised mathematical models of the topography of ganglion cells in the retina
      of macaque monkeys. The models consisted of a sum-of-three exponentials function
      fitted to measurements of ganglion cell density made on the nasal horizontal
      meridian, combined with known anisotropies across the horizontal and vertical
      meridians by means of elliptic interpolation to provide a full description of
      their density across the whole of the retinal surface. Integration using standard
      numerical techniques allowed the number of ganglion cells in arbitrary regions of
      the retina to be estimated. The topography of actual and effective total ganglion
      cell populations, and of primate alpha and gamma retinal ganglion cells, was
      modelled on previously published data. The models were used to test the
      hypothesis that the retinal projection to the striate cortex in macaque monkeys
      is peripherally scaled (i.e. merely reflects the eccentricity-dependent variation
      in density of ganglion cells in the retina) by comparing the cumulative
      proportion of ganglion cells with the cumulative proportion of cortical area as a
      function of eccentricity in the visual field. Discrepancies between the two
      curves indicated that the fovea and immediately surrounding retina are
      overrepresented in the striate cortex (i.e. there is more cortex per ganglion
      cell in and near the fovea than in the periphery), and the fact that the
      discrepancies persisted out to 25-50 degrees of eccentricity showed that the
      overrepresentation cannot be explained by the lateral displacement of foveal
      ganglion cells.

PMID- 8861080
TI  - Premature ovarian failure.
AB  - Premature ovarian failure (POF) is common, affecting approximately 1% of women.
      It is defined as gonadal failure before the age of 40 and patients may clinically
      present with either primary or secondary amenorrhoea. This review concentrates on
      the clinical aspects of POF, with sequential discussion on the aetiology and
      epidemiology, clinical manifestations and relevant investigations, concluding
      with an overview of management. In addition, the scientific basis for our current
      understanding of POF is summarized to provide a comprehensive overview of the
      diverse pathophysiological mechanisms that may underlie this disorder. Despite
      the heterogeneity of causes of POF, the fundamental treatment principles are the
      same. In this review the initiation of hormone replacement therapy in the younger
      woman and the importance of long term follow-up and treatment are emphasized.

PMID- 8861081
TI  - Transvaginal sonography of the endometrium in women with postmenopausal bleeding.
AB  - OBJECTIVE: The purpose of this study was to determine the value of screening
      transvaginal ultrasonography for the evaluation of endometrial abnormalities in
      women with postmenopausal bleeding. MATERIALS AND METHODS: 250 women with
      postmenopausal bleeding underwent transvaginal ultrasonographic examinations
      before undergoing dilatation and curettage. Women who had any pelvic symptoms or
      were on hormone replacement therapy were excluded. RESULTS: In 151 women, the
      histologic diagnosis was atrophic endometrium. In these patients, the mean
      endometrial thickness was 3.4 +/- 1.2 mm. In 24 patients with endometrial
      carcinoma, the mean endometrial thickness was 16.5 +/- 6.2 mm. The measurement
      included both endometrial layers (i.e. double layer). Thirty six cases of other
      pelvic pathologic conditions were discovered on ultra sonography. CONCLUSIONS: We
      believe that is reasonable to have a cutoff limit for normal postmenopausal
      endometrium at 5 mm. Endovaginal ultrasound is a valuable diagnostic instrument,
      as sensitive as dilatation and curettage, for detecting pathological conditions
      in the uterine mucosa.

PMID- 8861082
TI  - Female voice changes around and after the menopause--an initial investigation.
AB  - The views of 48 female and 24 male professional singers aged 40-74 years were
      sought regarding the occurrence of possible voice changes in around the fifth
      decade of life. The changes actually experienced were investigated to determine
      whether women's and men's voice changes were different, which might indicate that
      the menopause had an impact on the female voice. Respondents were approached via
      personal contacts and completed anonymous questionnaires that were returned by
      mail. Given the delicate nature of the study topic, no information was obtained
      on non-responders. Seventy-seven percent of the female singers and 71% of the men
      were of the opinion that the voice generally underwent changes at around the age
      of 50. The female singers placed greater emphasis on problems affecting the high
      registers and voice control than the men. Overall, 29% of the women had actually
      experienced negative voice changes at around age 50, as compared with 38% of the
      men. Both sexes reported huskiness, but the women seemed to have more frequent
      problems with voice emission, voice control and reaching their highest registers.
      In addition, 27 women reported that they had experienced voice changes during
      menstruation and five women stated that these had occurred during use of the oral
      contraceptive pill, which may have reflected the impact of other hormone-related
      factors. Despite the limitations of this initial investigation (the sample was
      small and selective), the broad findings indicated that the female voice
      undergoes specific changes at around the time of the menopause.

PMID- 8861083
TI  - Changes in the cortical and trabecular bone compartments with different types of
      menopause measured by peripheral quantitative computed tomography.
AB  - Our objective was to study the changes in the bone mineral density of the
      cortical and trabecular compartments with different types of menopause. A total
      of 153 normal postmenopausal women (mean age 48 +/- 5 years) were studied. The
      women were divided into three groups based on mean age at menopause: early
      menopause (menopause before 43 years), normal menopause (menopause at 44-52
      years), and late menopause (menopause after 52 years). The number of years since
      menopause was similar in all three groups (+/- 5 years). Cortical and trabecular
      bone mineral density was determined in all the women using peripheral
      quantitative computed tomography. Our results show that only the trabecular bone
      mineral density differed significantly among the groups (Kruskal-Wallis: P =
      0.0029). The women with early menopause had a lower trabecular bone density than
      the women with normal and late menopause (P = 0.0019 and P < 0.0001,
      respectively). Among the women with early menopause, 22 had experienced menopause
      before the age of 40 and 25 after the age of 40; there were significant
      differences in trabecular bone mineral density between these two subgroups (P <
      0.05). Trabecular bone mineral density, the only variable studied that varied
      among the groups, correlated significantly with the duration of reproductive life
      (simple linear regression: r = 0.340, P < 0.0001). In conclusion, these findings
      emphasize the importance of the duration of reproductive life as a determinant of
      bone mass in women.

PMID- 8861084
TI  - 17 beta-estradiol and norethisterone acetate in low doses as continuous combined
      hormone replacement therapy.
AB  - OBJECTIVES: To evaluate low doses of 17 beta-estradiol (E2) and norethisterone
      acetate (NETA) as continuous combined hormone replacement therapy (HRT) in their
      effects on vasomotor symptoms, bleeding episodes, endometrial histology and
      mastalgia. METHOD: Sixty postmenopausal women were randomly allocated to three
      treatment groups and were given 1 mg E2 and 0.25 mg NETA (A), 1 mg E2 and 0.5 mg
      NETA (B) and 2 mg E2 and 1.0 mg NETA (C) in daily doses. The treatment period was
      1 year. RESULTS: A similar statistically significant reduction of climacteric
      symptoms (P < 0.05) was found in all groups. Bleedings, mainly as spottings,
      occurred most commonly during the first treatment months. Fewer bleeding episodes
      and a higher percentage of amenorrhea was noted in group B compared to the other
      groups but did not reach statistical significance. All endometrial biopsies
      showed atrophy. Women in group A and B had less severe mastalgia (P < 0.05)
      compared to group C, given higher doses of steroids. CONCLUSION: Postmenopausal
      women taking 1 mg of E2 plus 0.5 mg NETA as continuous combined HRT reported a
      marked reduction of climacteric complaints and good bleeding control. No
      endometrial proliferation was detected after 1 year of treatment. This type of
      therapy may be beneficial especially for elderly women, in whom bleeding may be
      annoying.

PMID- 8861085
TI  - Transvaginal sonography in postmenopausal women treated with low-dose estrogens
      locally administered.
AB  - OBJECTIVE: The objective of this study was to determine the efficacy of low-dose
      estrogens, administered locally, in postmenopausal women with symptoms and signs
      of atrophic vaginitis. Transvaginal ultrasonography was performed for the
      evaluation of endometrial or ovarian abnormalities. MATERIALS AND METHODS: Fifty
      six healthy postmenopausal women with symptoms of atrophic vaginitis due to
      estrogen deficiency were examined with transvaginal ultrasound. The endometrial
      thickness, the uterus and the ovaries were measured before and after 6 months of
      treatment with low-dose estrogens. RESULTS: The mean endometrial thickness,
      before and after treatment was 3.1 +/- 0.8 mm and 3.1 +/- 1.2 mm respectively.
      The mean ovarian volume before treatment was 4.5 ml and there was no difference
      after treatment. There were no changes in uterine thickness during the treatment
      period. CONCLUSIONS: Our study, using transvaginal ultrasonography, has shown
      that low-dose estrogens, administered locally, give no sign of endometrial
      proliferation, measured as endometrial thickness, and do not alter the ovarian
      volume in postmenopausal volume.

PMID- 8861086
TI  - A comparative study of prescribing of hormone replacement therapy in USA and
      Europe.
AB  - OBJECTIVES: The use of hormone replacement therapy (HRT) has been shown to vary
      from one country to another through international studies of sample populations
      and by comparison of data obtained from comparable national studies. Drawing
      international prescribing comparisons is very difficult as data sources are few,
      incomplete and of uncertain accuracy and comparability. As an alternative to
      direct prescribing information, pharmaceutical sales information indicates
      medication used. This paper sought to demonstrate international differences in
      the use of HRT using an economic analysis methodology based on national
      pharmaceutical sales statistics. METHODS: A recognised economic analysis
      methodology was used to translate 1991/1992 pharmaceutical sales data into women
      treatment years of HRT used in each country. From this was calculated the
      percentage of the female population in each country, eligible for HRT, who would
      have been taking HRT. RESULTS: The results show a wide variance in the percentage
      of the eligible female population in each country calculated to have been taking
      HRT, from <1%-20%. The results indicated that HRT usage fell into three
      groupings: USA being the greatest user with UK and Scandinavian countries in the
      middle group and continental Europe having the lowest usage. CONCLUSIONS:
      National patterns of HRT usage, as calculated by this study, correlate well with
      those of other studies. Since similar morbidity could be expected as menopause is
      a naturally occurring event, not a disease, possible reasons for the variance in
      national prescribing patterns are discussed. The study indicates the need for
      further research on health beliefs and physicians' and women's attitudes to HRT
      in different countries to explain the variance in HRT usage, also considering
      access to healthcare, in particular women's health services. It confirms the
      validity of using economic analysis of pharmaceutical sales data as a proxy for
      prescribing data in the arena of prescribing research.

PMID- 8861087
TI  - Tibolone versus conjugated estrogens and sequential progestogen in the treatment
      of climacteric complaints.
AB  - OBJECTIVE: Tibolone has been shown to alleviate climacteric symptoms. This study
      was designed to compare the effect of tibolone (Livial, 2.5 mg daily) on
      different climacteric complaints and its impact on the endometrium, determined by
      vaginal ultrasound, with that of conjugated estrogens (Premarin, 0.625 mg daily)
      continuously for 6 months in combination with the progestogen medrogestone
      (Colpron, 2 x 5 mg daily for 12 days each month). METHODS: One hundred and twenty
      nine postmenopausal women were recruited and the severity of climacteric symptoms
      as well as endometrial thickness were recorded at the pre-trial examination and
      after 1, 3, and 6 months. RESULTS: With the exception of vertigo, mood
      depression, mood disorder, loss of libido, and dryness of skin, where tibolone
      was found to be more effective than conjugated estrogens/medrogestone,
      climacteric symptoms improved significantly in both groups over the 6-month study
      period. Endometrial thickness did not increase significantly in the tibolone
      group, whereas in the conjugated estrogens/medrogestone group there was a highly
      significant increase after 1 month and still a trend towards significance after 6
      months. Recurrence of vaginal bleeding occurred significantly less frequently in
      the tibolone group than in the comparison group. CONCLUSION: Tibolone seems to
      offer a complete treatment of the climacteric complaints whilst avoiding some of
      the problems associated with classical hormone replacement therapy.

PMID- 8861088
TI  - Decreased sexual interest and its relationship to body build in postmenopausal
      women.
AB  - OBJECTIVES: The relationship between body build, androgen levels and changes in
      sexual interest after menopause was investigated in 171 postmenopausal women from
      Vienna, Austria. METHODS: All women were interviewed using a structured
      questionnaire. Body build was determined by employing five absolute body
      dimensions and four anthropometric indices. RESULTS: Body weight, as well as the
      amount of subcutaneous centripetal fat (such as in the chest, waist and hip
      region), were statistically significantly related to the degree of reduced sexual
      interest. Corpulent and heavy women suffered far more frequently from a severe
      decrease in sexual interest after menopause. Statistically significant
      associations between androgen levels and decrease in sexual interest could not be
      demonstrated. CONCLUSIONS: Reduced sexual interest is associated with a kind of
      body type not corresponding to the culture-specific beauty ideals of our society,
      first of all evident in women whose menopause occurred relatively early.

PMID- 8861089
TI  - Sociological and behavioural characteristics of perimenopausal women with an
      express attitude to hormone substitution therapy.
AB  - OBJECTIVES: The objective of the study is to demonstrate differences in behaviour
      and in sociological characteristics between women wanting hormone replacement
      therapy (HRT) and women refusing such treatment. METHODS: From a study base of
      6189 women, 413 perimenopausal women with an express positive or negative
      attitude towards the use of HRT were interviewed on sociological and behavioural
      characteristics. Checks against bias were performed by analysis of reluctant
      participants, identified as women who either did not agree to participate until
      they received at least one reminder, or who dropped out immediately after the
      interview. RESULTS: Women wanting HRT had higher levels of education, were less
      often childless, and were more frequent solarium users than women refusing this
      treatment. There were no differences in marital status, employment status, the
      average tea, coffee, wine and cigarette consumption, sun exposure, frequencies of
      travels abroad, or number of family cars, summer houses or boats. No difference
      in present smoking status was demonstrated but the estrogen users were more
      frequently past or present smokers. CONCLUSIONS: It is suggested that lack of
      knowledge of HRT may sometimes be the cause of rejecting it, or may influence on
      the compliance regarding its use. Familiarity with the use of the health system
      for other reasons than disease may promote the use of HRT. It is demonstrated
      that the observed patterns do not originate from self-selection bias.

PMID- 8861090
TI  - Climacteric symptoms in a postmenopausal Czech population.
AB  - OBJECTIVES: To assess the prevalence of climacteric symptoms and the use of
      hormone replacement therapy in a former eastern European country. All 55-, 57-,
      59- and 61-year-old women in Kladno in the Czech Republic were asked to
      participate in the study. METHOD: In 1993, 1505 women in Kladno of the Czech
      Republic were sent a postal questionnaire concerning age at menopause and their
      climacteric symptoms. RESULTS: Answers were received from 799 women (53%); 98%
      were postmenopausal. The median age at spontaneous menopause was 50 years, 49.5
      years among women smoking at least 5 cigarettes/day and 51.0 years among non
      smokers (P < 0.05). About every fifth woman smoked. Totally 22% of the women had
      undergone hysterectomy and/or oophorectomy and 3% had been treated for a
      gynaecological malignancy. The majority of the women (58%) reported ongoing
      vasomotor symptoms; half of them had moderate to severe vasomotor symptoms. In
      all, 79% of the women reported ever having vasomotor symptoms. Only 3% of the
      women had ever tried hormone replacement therapy (HRT) and one woman had current
      treatment. Dysuria was reported by 22% and 4% had recurrent urinary tract
      infections; 70% of the women had a partner and 50% were sexually active. Reasons
      for not being sexually active were mostly lack of a partner, loss of sexual
      desire or partner's disease or impotence. CONCLUSION: Climacteric symptoms
      including vasomotor and urogenital symptoms had the same prevalence in the Czech
      Republic as previously reported in other Western Countries. Only a few women had
      tried HRT. Smokers had a slightly earlier menopause.

PMID- 8861091
TI  - Hormonal, syndromal and EEG mapping studies in menopausal syndrome patients with
      and without depression as compared with controls.
AB  - The aim of the study was to investigate brain function in menopausal depression
      by EEG mapping, as compared with menopausal syndrome patients without depression
      and normal controls, and to correlate neurophysiological with clinical and
      hormonal findings in order to elucidate the pathogenesis of depression in the
      menopause. METHODS: One hundred and twenty-nine menopausal women, aged 45-60
      years, with no previous hormonal replacement therapy were investigated in regard
      to hormones (estradiol [E2], follicle stimulating hormone [FSH]), clinical
      symptomatology (Kupperman Index [KI], Hamilton depression score [HAMD]) and brain
      function (EEG mapping). Based on KI and DSM-III-R research criteria for major
      depression, 3 groups were available for statistics (after removal of protocol
      violators): group A had a KI of <15 and no depression (n = 29); group B had a KI
      of > or = 15 and no depression (n = 29) and group C had a KI of > or = 15 and
      fulfilled the criteria for major depression (n = 60). RESULTS: EEG maps of
      depressed patients demonstrated less total power and absolute power in the delta,
      theta and beta band, more relative delta and less alpha power as well as a slower
      delta/theta and faster alpha and beta centroid than controls, suggesting a
      vigilance decrement. Group B did not differ from group A. Correlation maps showed
      significant relationships between estradiol levels and EEG measures (the lower
      the E2, the worse the vigilance) and between the EEG measures and the Hamilton
      depression (HAMD) score (the worse the vigilance, the higher the depression
      score). There were no correlations between the hormones E2 and FSH and the
      syndromes KI and HAMD. In the target variable, the asymmetry index, depressed
      patients showed less alpha power over the right than left frontal lobe, whereas
      normal controls exhibited the opposite. Group B did not differ from group A. The
      frontal asymmetry index was significantly correlated with the Hamilton depression
      score and suggests right frontal hyper- and left frontal hypoactivation in
      depression. CONCLUSIONS: Although hormonal findings are not directly linked to
      psychic changes, low estradiol levels do contribute to a decreased vigilance at
      the neurophysiological level , which is in turn correlated with higher depressive
      and menopausal symptomatology at the behavioural level. Depression is further
      correlated to a right frontal hyper- and left frontal hypoactivation.

PMID- 8861092
TI  - Transcription factor hoxa-5 is taken up by cells in culture and conveyed to their
      nuclei.
AB  - Homeoproteins are transcription factors known to be involved in the early
      patterning of the nervous system and in lineage decisions. While studying a
      possible role for homeoproteins at later stages of neuronal differentiation, we
      observed that the Antennapedia homeodomain is internalized by neurons,
      translocated to their nuclei, and enhances neurite outgrowth. Studies with mutant
      homeodomains showed that neurite elongation by post-mitotic vertebrate neurons is
      regulated by homeoproteins. An intriguing possibility suggested by these results,
      is that full length homeoproteins might be able to translocate through neuronal
      membranes. We now report that the entire Hoxa-5 homeoprotein is taken up by
      fibroblasts and neurons in culture and conveyed to their nuclei. Internalization
      occurs at 4 and 37 degrees C, and at concentrations as low as 10 pM compatible
      with a physiological mechanism.

PMID- 8861093
TI  - 'Regeneration' of wing bud stumps of chick embryos and reactivation of Msx-1 and
      Shh expression in response to FGF-4 and ridge signals.
AB  - We examined systematically the ability of chick limb bud stumps to regenerate
      distal structures when fibroblast growth factor (FGF)-4 is applied. When
      amputations were made within 600 mu m of the tip and FGF-4 applied either
      posteriorly or both apically and posteriorly, outgrowth of stump tissues occurred
      and a virtually complete skeleton developed. 'Regeneration' of distal structures
      was correlated with reactivation of Msx-1 and Shh expression. At proximal
      amputation levels where FGF-4 did not lead to 'regeneration', neither Msx-1 nor
      Shh expression was induced. We also grafted cells from progressively more
      proximal levels of mouse limb buds to chick wing bud tips beneath the apical
      ridge and the pattern of reactivation of Msx-1 expression along the proximal
      distal axis of the limb buds was similar to that found in chick limb buds.

PMID- 8861094
TI  - A novel MAP kinase phosphatase is localised in the branchial arch region and tail
      tip of Xenopus embryos and is inducible by retinoic acid.
AB  - Using a differential display strategy, we have isolated a cDNA corresponding to a
      mRNA which is induced by retinoic acid treatment of late gastrula Xenopus
      embryos, and much more strongly induced by retinoic acid and cycloheximide. The
      cDNA, designated X17C, encodes a novel mitogen-activated protein (MAP) kinase
      phosphatase of 378 amino acid residues which is only distantly related to other
      known MAP kinase phosphatases. In normal embryogenesis, the X17C mRNA is
      expressed after the midblastula transition and accumulates during gastrulation.
      In neurula and tailbud stage embryos the mRNA is localised in two domains, one in
      the anterior region of the embryo, and one at the tail tip. When expressed from
      synthetic mRNA injected into oocytes, the X17C protein is found within the
      cytosolic fraction and not in the nucleus. The X17C protein dephosphorylates and
      inactivates Xenopus MAP kinase in oocytes stimulated to undergo maturation by
      progesterone. We indicate the application of X17C as a tool for interfering with
      MAP kinase signaling in somatic cells of embryos, using FGF receptor-mediated MAP
      kinase activation in animal cap explants.

PMID- 8861095
TI  - Xotx genes in the developing brain of Xenopus laevis.
AB  - The vertebrate Otx gene family is related to otd, a gene contributing to head
      development in Drosophila. We previously reported on the expression of Xotx2
      gene, homologous to the murine Otx2 gene, during early Xenopus development. In
      the present paper we report an extensive analysis of the expression pattern of
      Xotx2 during later stages of development and also the cloning and developmental
      expression of two additional Otx Xenopus genes, Xotx1 and Xotx4. These latter two
      genes bear a good degree of homology to murine Otx1, higher for Xotx1 than for
      Xotx4. Both these genes are expressed in the forebrain and midbrain regions and
      their developmental patterns of expression are very similar, although not
      perfectly superimposable. Spatial and temporal expression patterns of the three
      Xotx genes suggest that they may be involved in the early subdivision of the
      rostral brain, providing antero-posterior positional information within the most
      anterior districts of the neuraxis. The three Xotx genes are expressed in all the
      developing sense organs of the head, eyes, olfactory system and otic vesicles. By
      in situ hybridization the earliest detectable expression is found in anterior
      mesendoderm for Xotx2, and in presumptive anterior neuroectoderm for Xotx1 and
      Xotx4. In addition, we examined whether Xotx1 is expressed in exogastrulae,
      finding that Xotx1 expression can be activated in the apparent absence of
      vertical signals of neural induction.

PMID- 8861096
TI  - The fu gene discriminates between pathways to control dpp expression in
      Drosophila imaginal discs.
AB  - The genes decapentaplegic (dpp) and wingless (wg), which encode secreted factors
      of the TGF-beta and Wnt families, respectively, are required for the proper
      development of the imaginal discs. The expression of these genes must be finely
      regulated since their ectopic expression induces overgrowth and pattern
      alterations in wings and legs. Genes like patched (ptc) and costal-2 (cos-2), and
      the gene encoding the catalytic subunit of the protein kinase A gene (pkA) are
      required to restrict dpp and wg expression in their proper positions. We show
      here that some mutations in the cubitus interruptus (ci) gene also show ectopic
      dpp expression in the wing disc. We have also analyzed the functional hierarchy
      between these genes and the gene fused (fu), in the activation of dpp by the
      hedgehog (hh) signal. fu is required to transmit the hh signal in imaginal discs,
      since fu mutations rescue the phenotype due to the ectopic hh expression or to
      the lack of ptc activity. fu is also required for the activation of engrailed
      (en) caused when hh is ectopically activated in the wing disc. By contrast, fu
      mutations do not rescue the phenotypic consequences of the abnormal ci, cos-2 or
      pkA activity. Although fu, cos-2 and ci probably form part of the same pathway
      that controls dpp expression, pkA probably controls dpp transcription by a
      different pathway.

PMID- 8861097
TI  - Isolation and developmental expression analysis of Enx-1, a novel mouse Polycomb
      group gene.
AB  - Members of the Polycomb group (Pc-G) of genes encode transcriptional regulators
      that control the expression of key developmental effector genes in Drosophila
      melanogaster. Although multiple Pc-G genes have been identified and characterized
      in Drosophila, information about these important regulatory proteins in
      vertebrates, including their precise expression patterns, has remained scarce. We
      report here the cloning of Enx-1, a novel vertebrate Pc-G gene, which encodes the
      murine homolog of the Drosophila Enhancer of zeste (E(z)) gene. Drosophila E(z)
      controls the expression of several homeobox genes as well as some segmentation
      genes and its disruption causes multiple phenotypes in Drosophila development.
      Analysis of the primary structure of murine Enx-1 reveals the conservation of
      several regions, including the previously described SET domain and a newly
      defined CXC domain. In addition, we find the SET domain to be conserved in
      evolutionarily distant species ranging from vertebrates to plants and fungi. The
      expression pattern analysis of Enx-1 reveals ubiquitous expression throughout
      early embryogenesis, while in later embryonic development Enx-1 expression
      becomes restricted to specific sites within the central and peripheral nervous
      system and to the major sites of fetal hematopoiesis. In adult stages we also
      find Enx-1 expression to be restricted to specific tissues, including spleen,
      testis and placenta.

PMID- 8861098
TI  - Comparison of MSX-1 and MSX-2 suggests a molecular basis for functional
      redundancy.
AB  - This study examines the biochemical properties of two members of the murine MSX
      family, MSX-1 and MSX-2, which have been implicated to have partially overlapping
      functions during embryogenesis. Our analyses show that MSX-1 and MSX-2 share many
      features in common including their DNA binding and transcriptional properties. In
      particular, MSX-1 and MSX-2 interact with a common consensus DNA site, and
      exhibit similar DNA binding site preferences. However, MSX-2 has a higher
      apparent affinity for DNA, and the distinction between MSX-1 and MSX-2 resides in
      their differing sequences N-terminal to the homeodomain. With respect to their
      transcriptional properties, both MSX-1 and MSX-2 function as repressors and share
      the distinct property that they do so independently of their consensus DNA
      binding sites. However, MSX-1 is a more potent repressor, and the difference
      between these proteins also maps to their N-terminal regions. Similarly, the
      expression patterns of Msx-1 and Msx-2 as examined by whole mount in situ
      hybridization are related but not identical. Thus, Msx-1 and Msx-2 are co
      expressed in the limbs, neural tube, and branchial arches; however, Msx-1 has a
      broader expression pattern overall and is expressed uniquely in certain embryonic
      regions. These features suggest that these members of the Msx family are
      'equivalent but not equal' and that their proposed redundancy may be achieved via
      distinct biochemical mechanisms that yield a similar functional outcome.

PMID- 8861099
TI  - The murine homeobox gene Msx-3 shows highly restricted expression in the
      developing neural tube.
AB  - The mouse homeobox-genes Msx-1 and Msx-2 are expressed in several areas of the
      developing embryo, including the neural tube, neural crest, facial processes and
      limb buds. Here we report the characterisation of a third mouse Msx gene, which
      we designate Msx-3. The embryonic expression of Msx-3 was found to differ from
      that of Msx-1 and -2 in that it was confined to the dorsal neural tube. In
      embryos with 5-8 somites a segmental pattern of expression was observed in the
      hindbrain, with rhombomeres 3 and 5 lacking Msx-3 while other rhombomeres
      expressed Msx-3. This pattern was transient, however, such that in embryos with
      18 or more somites expression was continuous throughout the dorsal hindbrain and
      anterior dorsal spinal cord. Differentiation of dorsal cell types in the neural
      tube can be induced by addition of members of the Tgf-beta family. Additionally,
      Msx-1 and -2 have been shown to be activated by addition of the Tgf-beta family
      member Bmp-4. To determine if Bmp-4 could activate Msx-3, we incubated embryonic
      hindbrain explants with exogenous Bmp-4. The dorsal expression of Msx-3 was seen
      to expand into more ventral regions of the neurectoderm in Bmp-4-treated
      cultures, implying that Bmp-4 may be able to mimic an in vivo signal that induces
      Msx-3.

PMID- 8861100
TI  - Characterization of an immunodeficiency mutant in Drosophila.
AB  - Drosophila immunity and embryogenesis appear to be linked by an evolutionarily
      ancient signalling pathway, which includes the Rel-domain transcription factors
      Dif and dorsal, respectively, as well as a common inhibitor, cactus. Previous
      genetic screens have centered on maternal mutants that disrupt the dorsal
      pathway. In an effort to identify additional components that influence Rel-domain
      gene function we have conducted a search for immunodeficiency mutants in
      Drosophila. One such mutant, which maps near the Black cells (Bc) gene, causes a
      severe impairment of the normal immune response, including attenuated induction
      of several immunity genes. Survival assays indicate a positive correlation
      between the induction of these genes, particularly diptericin, and resistance to
      bacterial infection. These studies are consistent with the notion that insect
      anti-microbial peptides work synergistically by binding distinct targets within
      infecting pathogens. Evidence is also presented that non-specific acquired
      immunity results from the persistence of bacterial metabolites long after primary
      infection. We discuss the potential usefulness of this study with regard to the
      identification of conserved components of Rel signalling pathways.

PMID- 8861101
TI  - Expression of the winged helix genes fkh-4 and fkh-5 defines domains in the
      central nervous system.
AB  - The 'winged helix' or 'forkhead' transcription factor gene family is defined by a
      common 100 amino acid DNA binding domain which is a variant of the helix-turn
      helix motif. Here we describe the structure and expression of the mouse fkh-4 and
      fkh-5 genes. The two genes encode proteins of 427 and 324 amino acids,
      respectively, with highly similar winged helix domains. Both genes are expressed
      in adjacent domains in the developing diencephalon from the headfold stage
      onward. Linkage analysis localised fkh-5 to chromosome 9 at 34.5 centiMorgans
      (cM) and fkh-4 to chromosome 19 at 10.5 cM. The potential relationship of the two
      genes to the mouse mutations staggerer and small thymus (for fkh-5) and muscle
      deficient (for fkh-4) is discussed.

PMID- 8861102
TI  - Spinal cord lactate concentration during chemical stimulation of the nucleus
      tractus solitarii in anesthetized rats.
AB  - This study was conducted to determine the mechanism of spinal cord blood flow
      (SCBF) decrease following the nucleus tractus solitarii (NTS) activation. In
      urethane-anesthetized, paralyzed and artificially ventilated rats, neurons in the
      NTS were chemically stimulated by microinjection of L-glutamate (1.7 nmol; 50 nl)
      and the lactate concentration, one of indicators of local neuronal metabolism, in
      the spinal cord was monitored in real time using an enzyme electrode. Before the
      chemical stimulation study, the responses of the enzyme electrode and its
      specificity were tested in vitro and in vivo. The electrode responded to step
      changes in lactate concentration and a calibration plot and regression line were
      obtained in vitro. The lactate concentration was significantly (P < 0.01)
      increased during induced apnea in vivo (n = 8). The lactate concentration in the
      spinal cord was not significantly changed by chemical stimulation of the NTS when
      arterial blood pressure (ABP) remained above the lower limit of spinal cord
      autoregulation (n = 21). When chemical stimulation of the NTS decreased ABP to
      below the lower limit of autoregulation (n = 18), the lactate concentration in
      the spinal cord was significantly (P < 0.01) increased. This may only be due to
      hypotensive effects because the lactate concentration was also significantly (P <
      0.01) increased when the ABP was passively decreased below the lower limit of
      autoregulation by controlled hemorrhage in intact (n = 11) and sinoaortic
      denervated rats (n = 10). Intravenous lactate injection produced no significant
      increase in the current from the enzyme electrode in the spinal cord (n = 4).
      Using the electrode with inactivated enzyme solution, the current from the
      electrode did not change with the increase in lactate in the spinal cord. These
      findings indicate that the enzyme electrode can detect rapid changes of lactate,
      a product of anaerobic metabolism. These results also indicate that the spinal
      cord vasoconstrictor response elicited by chemical stimulation of the NTS, which
      was performed above the lower limit of spinal cord autoregulation in our previous
      study, may be due to neurogenic regulatory mechanism, but not to the secondary
      effects of changes in metabolism.

PMID- 8861103
TI  - The distribution of two calcium binding proteins, calbindin D-28K and
      parvalbumin, in the entorhinal cortex of the adult mouse.
AB  - The immunohistochemical localization of two specific calcium binding proteins,
      parvalbumin (PV) and calbindin D-28K (CB), were examined in the entorhinal cortex
      (EC) of the adult mouse. The PV and CB immunoreactivities exhibited a conspicuous
      regional and laminar distribution in the EC. The overall immunostaining pattern
      of PV and CB appeared to be complementary in the EC, especially in the medial
      entorhinal area (MEA). In the dorsal MEA, although layer 2 showed intense PV and
      CB immunostaining, the PV immunoreactivity was denser in layers 3, 5 and 6a than
      in layers 4 and 6b, whereas the CB immunoreactivity was denser in layers 4 and 6b
      than in layers 3, 5 and 6a. Moreover, we recognized the dorsoventral gradation of
      the PV and CB staining that is, in the dorsal to ventral direction, the intensity
      of the PV immunostaining in layers 2, 3, 5 and 6a gradually decreased whereas
      that of the CB immunostaining in those layers gradually increased. In addition, a
      similar dorsoventral gradation was also observed in the number of PV
      immunoreactive (PV-IR) and CB-IR neurons in layer 3. In layer 2 of the MEA, the
      CB-IR neurons were clustered, while displaying a patch-like pattern which could
      not be recognized in either Nissl staining or PV staining. In contrast, layer 2
      of the LEA was separated into two sublayers, the superficial sublayer 2a and the
      deeper sublayer 2b; both of these sublayers consisted of cell clusters recognized
      by Nissl staining. These sublayers showed a prominent difference in their CB
      immunoreactivity; the cells in the layer 2a clusters were CB negative, whereas
      the cells in the layer 2b clusters were CB-IR. Furthermore, we also recognized a
      particular region at the most medial part of the MEA, where layer 2 was different
      from the other portion of the MEA regarding CB immunoreactivity and the cells
      containing another calcium binding protein, calretinin, were clustered in layer
      3. Both the adjacent section technique and the fluorescent double-staining
      technique clearly revealed that a relatively large number of presumable
      interneurons contained both PV and CB immunoreactivities. Furthermore, the three
      neuron groups that were immunoreactive for both PV and CB, immunoreactive for PV
      alone and immunoreactive for CB alone were heterogeneous in their structural
      features such as shape and size, and no particular difference was found in their
      structural features among these three groups.

PMID- 8861104
TI  - Cell surface-associated extracellular distribution of a neural proteoglycan, 6B4
      proteoglycan/phosphacan, in the olfactory epithelium, olfactory nerve, and cells
      migrating along the olfactory nerve in chick embryos.
AB  - The immunocytochemical and immuno-electron microscopic distribution of a neural
      proteoglycan (PG) was investigated with a monoclonal antibody, MAb 6B4, in the
      olfactory epithelium, the olfactory nerve, and the cells originating the
      epithelium and migrating along the olfactory nerve toward the forebrain in chick
      embryos. The PG recognized by MAb 6B4, that is 6B4 PG, in the brain of early
      postnatal rats, is identical to phosphacan. In chick embryos, immunoreactivity to
      6B4 PG appeared on embryonic day (ED) 3-3.5 in a thin layer beneath the olfactory
      epithelium. It disappeared immediately, then becoming apparent in the bundles of
      the olfactory nerve. The immunoreactivity in the nerve bundles gradually
      increased during ED 5-11. On the other hand, cell surface-associated
      extracellular localization of the immunoreactivity was seen in the olfactory
      epithelium on ED 6 and afterwards. Immunofluorescent double-labeling of 6B4 PG
      and gonadotropin-releasing hormone (GnRH) revealed that the cell bodies of both
      GnRH-containing cells and other cells migrating along the olfactory nerve were
      surrounded by a rim immunoreactive to the PG. Under an electron microscope, the
      surfaces of the cell bodies and of the neurites in the nerve bundles were
      surrounded by deposits immunoreactive to 6B4 PG. These results indicate that 6B4
      PG in chick embryos is one type of cell surface-associated extracellular matrix
      molecule, and that 6B4 PG covered the surfaces of migrating cells and of
      elongating olfactory nerve. The cell surface-associated extracellular
      localization of 6B4 PG found in the nasal region, taken together with the binding
      properties of this PG with cell adhesion molecules shown in rat brains, suggested
      that 6B4 PG played a role in guiding the migration of cells along the olfactory
      nerve in chick embryos.

PMID- 8861105
TI  - Induction of tissue transglutaminase in rat superior cervical sympathetic ganglia
      following in vitro stimulation of retinoic acid.
AB  - The addition of retinoic acid (RA, 50 nM) to Dulbecco's modifed Eagle's medium
      containing 1.0 percent bovine serum albumin and 50 mu g/l of gentamicin markedly
      increased the activity of a Ca(2+) -dependent tissue transglutaminase (TGase)
      (ca. 3.2-fold), which stabilizes newly formed protein assemblies at the sites of
      synapses, in isolated rat superior cervical sympathetic ganglia (SCG), which is
      abundant in synapses, following in vitro aerobic incubation for 3 h at 37 degrees
      C. An isomer of RA, 13-cis-RA (50 nM), showed the same tendency but rather lesser
      magnitude (ca. 1.7-fold) in ganglionic TGase activation. Also, retinal (50 nM), a
      precursor of RA, had a little effect on TGase stimulation (ca. 1.5-fold) in SCG.
      The RA-induced enhancement of ganglionic TGase activity was completely eliminated
      in the presence of either actinomycin D (1.0 mu g/ml), a depressant of molecular
      transcriptional activity, or a potent inhibitor of protein synthesis,
      cycloheximide (10 mu g/ml). Kinetic analyses show that the stimulation of
      ganglionic TGase activity evoked by RA addition was associated with only an
      increase in V max value (ca. 3.3-fold) without change in Km value. Thus, the
      enzyme protein of TGase might be synthesized de novo in the ganglia in response
      to RA. The RA-induced activation effect of ganglionic TGase almost disappeared
      (ca. 1.3-fold) 1 week following denervation, by which time preganglionic
      cholinergic nerve terminals were degradated. In axotomized SCG, where sympathetic
      neurons were degenerated and reactive proliferation of glial cells was in
      progress, the RA-evoked increase in ganglionic TGase activity was attenuated (ca.
      1.3-fold). These findings imply that some retinoids, especially RA effectively
      participate in the cholinergic potentiation of synaptic activity.

PMID- 8861106
TI  - The synaptic interrelationships between primary afferent terminals, cuneothalamic
      relay neurons and GABA-immunoreactive boutons in the rat cuneate nucleus.
AB  - The present study described an ultrastructural synaptic configurations between
      primary afferent terminals (PATs), cuneothalamic relay neurons (CTNs) and GABA
      immunoreactive (GABA-IR) boutons in the cuneate nucleus of rats using
      cervicothoracic dorsal rhizotomies, retrograde transport of wheat germ agglutinin
      conjugated with horseradish peroxidase complex (WGA-HRP) and anti-GABA immunogold
      labelling methods. With this procedure, direct synaptic relationships between the
      PATs, CTNs and GABA-IR boutons have been demonstrated. The most remarkable
      feature was the observation whereby an immunogold-labelled GABA-IR bouton was
      presynaptic to a WGA-HRP labelled dendrite of CTN and a degenerating PAT; the
      same PAT was in turn presynaptic to the HRP-labelled dendrite. This was evident
      in ten out of a total of 133 synaptic configurations that were closely
      scrutinized. Results of this study support the concept that GABA-IR boutons are
      not only involved in presynaptic inhibition on the primary afferent input to the
      cuneothalamic relay neurons, but also exert a simultaneous postsynaptic
      inhibition on these cells.

PMID- 8861107
TI  - Involvement of nitric oxide in acute spinal cord injury: an immunocytochemical
      study using light and electron microscopy in the rat.
AB  - The possibility that nitric oxide participates in the pathophysiology of spinal
      cord injury was examined using a constitutive isoform of neuronal nitric oxide
      synthase immunoreactivity in a rat model. Spinal cord trauma was produced by
      making an incision into the right dorsal horn of the T10-11 segments. Five h
      after trauma, a marked upregulation of NOS-immunostained neurons was seen in the
      perifocal T9 and T12 segments of the cord. The immunolabelling was most
      pronounced in the dorsal horn of the ipsilateral side. Topical application of an
      antiserum to nitric oxide synthase (NOS) 2 min after injury prevented the trauma
      induced upregulation of NOS-immunoreactivity. In contrast, application of
      preabsorbed serum or L-NAME, an inhibitor to NOS, was ineffective in reducing the
      induction of NOS-immunoreactivity. Trauma caused a marked expansion of the cord
      and resulted in marked cell changes. This expansion and cell reaction was
      significantly reduced following application of NOS antiserum but it was not seen
      after application of preabsorbed antiserum or L-NAME. Our results for the first
      time show that a focal trauma to the spinal cord has the capacity to upregulate
      neuronal NOS immunoreactivity and that application of NOS antiserum has a neuro
      protective effect. This indicates that nitric oxide is somehow involved in the
      pathogenesis of secondary injuries after spinal cord trauma.

PMID- 8861108
TI  - The sites of origin and termination of afferent and efferent components in the
      lingual and pharyngeal branches of the glossopharyngeal nerve in the Japanese
      monkey (Macaca fuscata).
AB  - Afferent and efferent components in the lingual and pharyngeal branches of the
      glossopharyngeal nerve (Li and Ph) of the Japanese monkey (Macaca fuscata) were
      examined. After injecting wheat germ agglutinin-conjugated horseradish peroxidase
      (WGA-HRP) unilaterally into the central cut end of the Li and Ph, or into the
      stylopharyngeal muscle, labeled neuronal cell bodies and terminal labeling were
      observed in the medulla oblongata, peripheral ganglia of the glossopharyngeal and
      vagus nerves, and cervical ganglia of the sympathetic trunk. The following
      conclusions were deduced from the results. The Li contains efferent fibers from
      the inferior salivatory nucleus, and superior cervical ganglion. The afferent
      fibers in the Li are composed mainly of peripheral processes of ganglion neurons
      in the superior and petrous ganglia of the glossopharyngeal nerve, and
      additionally of those of ganglion neurons in the jugular ganglion of the vagus
      nerve. The afferent fibers in the Li terminate mainly in the lateral division of
      the nucleus of the solitary tract, and additionally in the dorsal aspect of the
      lateral marginal region of the interpolar spinal trigeminal nucleus. The Ph is
      mainly composed of efferent fibers from the ambiguous nucleus and superior
      cervical ganglion; only a small number of afferent fibers from the sensory
      ganglia of the glossopharyngeal and vagus nerves are contained in the Ph.
      Stylopharyngeal motoneurons are distributed in the retrofacial part of the
      ambiguous nucleus.

PMID- 8861109
TI  - Reduction in the number of NADPH-diaphorase-positive cells in the cerebral cortex
      and striatum in aged rats.
AB  - Nitric oxide (NO) plays an important role as a diffusible messenger in learning
      and memory. To determine whether changes in NO production in the brain may be
      involved in aging-associated brain dysfunction, we measured the performance of
      aged rats in a radial arm maze task, and carried out histochemical examination of
      the changes in NADPH diaphorase (NADPH-d)-containing neurons in the brains of
      aged rats. The performance of aged rats (30 months old) in a radial arm maze task
      was significantly impaired compared to the performance of young rats (3 months
      old). The number of neurons containing NADPH-d reactivity in the cerebral cortex
      and striatum of aged rats was significantly reduced, by approximately 50 and 30
      percent, respectively, compared to that in young rats. NO synthase activity in
      discrete brain regions of aged rats, i.e., in the cerebral cortex, striatum and
      hippocampus was not different from that in young rats, although the activity in
      the cerebellum of aged rats was significantly lower than that in young rats.
      These results suggest that the reduction in the number of NADPH-d-positive cells
      in the brains of aged rats may be involved in aging-associated learning
      impairment in rats.

PMID- 8861110
TI  - Immunocytochemical localization of heme oxygenase-2 in the rat cerebellum.
AB  - Carbon monoxide (CO) is a gas that can permeate biological membranes and it has
      been suggested that the gas plays a signaling role in the brain by activating
      soluble guanylyl cyclase (sGC). CO is generated by heme oxygenase during the
      conversion of heme to biliverdin. In this study, we raised an antiserum against
      the chemically synthesized amino-terminal fragment of heme oxygenase-2 (HO-2) and
      studied the distribution of this enzyme in the rat cerebellum by an
      immunocytochemical method. Immunoreactivity specific for HO-2 was observed only
      in neurons. In the Purkinje cells and the basket cells of the cerebellum,
      immunoreactivity was detected in the dendrites and the somata but not in the axon
      terminals, suggesting that CO might be liberated primarily from the dendrites and
      somata rather than from the axons in this region of the rat brain.

PMID- 8861111
TI  - Preventive effects of bifemelane hydrochloride on decreased levels of muscarinic
      acetylcholine receptor and its mRNA in a rat model of chronic cerebral
      hypoperfusion.
AB  - Changes in muscarinic acetylcholine receptor (mACh-R) binding and muscarinic
      cholinergic m1 receptor (m1-R) mRNA levels were determined in a rat model of
      cerebral hypoperfusion in which hypoperfusion was induced by permanent bilateral
      occlusion of the common carotid arteries. After 6 weeks of hypoperfusion, mACh-R
      binding activity was significantly reduced in the frontal cortex (79.0 percent, P
      <0.01), striatum (74.2 percent, P < 0.01) and hippocampus (78.6 percent, P <
      0.01), and the m1-R mRNA levels in the frontal cortex (86.6 percent, P < 0.05)
      and striatum (89.4 percent, P < 0.05) compared with sham-operated control.
      Repeated administration of bifemelane hydrochloride (15 mg/kg/day, p.o., once a
      day from the day of operation for 6 weeks) prevented the hypoperfusion-induced
      loss of mACh-R binding and m1-R mRNA levels above described. Since the central
      cholinergic systems play an important role in learning and memory, these findings
      suggest that bifemelane hydrochloride is useful to treat and/or prevent vascular
      dementia which is closely related to cerebral hypoperfusion.

PMID- 8861112
TI  - Transplantation of human fetal striatum into a rodent model of Huntington's
      disease ameliorates locomotor deficits.
AB  - Previous studies have demonstrated that syngeneic transplants of striatal tissue
      can ameliorate locomotor deficits in rodent models of Huntington's disease (HD).
      In the present study, we have examined whether human to rat xenografts of fetal
      striatal tissue can exert a similar recovery of function. Rodents with unilateral
      striatal lesions were transplanted with human striatal cells from a donor 14
      weeks post-conception, and subsequently displayed a progressive decrease in
      rotational asymmetry in comparison to sham (saline) transplanted animals.
      Histological analysis revealed acetylcholinesterase (AChE)-positive fibers and
      NADPH-diaphorase (NADPH-d)-positive neurons within transplanted tissue. These
      results suggest that human fetal striatum at a gestational age of 14 weeks may
      potentially be useful as a source of donor tissue for transplantation in the
      treatment of HD.

PMID- 8861113
TI  - Expression of mRNA for a neuronal differentiation factor, TA2O, in developing rat
      brains.
AB  - In our previous study, a novel factor, TA2O, was isolated from NGlO8-l5 cells.
      The TA2O mRNA was increased by stimulation which also induced neuronal
      differentiation. Neuronal cells overexpressed with TA2O extended long neurites
      and stopped cell growth (Tohda et al., 1995, Neurosci. Res., 23: 21-27). We
      investigated the expression pattern of TA2O mRNA in developing rat brains to
      predict physiological roles of TA2O. TA2O mRNA began to increase between
      embryonic days 13 and 16. TA2O mRNA was observed mainly in neocortical,
      hippocampal and precerebellar neuroepithelium on embryonic day 16. Although the
      level of TA2O mRNA in the cerebral cortex was higher before birth than after
      birth, the level in cerebellar Purkinje cells increased gradually even after
      birth. The high expression level of TA2O mRNA in the hippocampus was maintained
      before and after birth. Thus, TA2O was expressed highly in brain regions in which
      neurons were changing morphologically and qualitatively, suggesting that TA2O may
      be involved in neuronal formation in vivo.

PMID- 8861114
TI  - Effects of judgement process on motor evoked potentials in Go/No-go hand movement
      task.
AB  - We examined the motor evoked potentials (MEP) of the forearm muscles following
      transcranial magnetic stimulation after the Go/No-go reaction-time hands movement
      in ten normal subjects. Facilitation of MEP of the agonistic muscles and
      suppression of MEP of the antagonistic muscles were recognized during the 'Go'
      session, while the MEPs of both muscles were markedly suppressed in the 'No-go'
      session. We considered that this MEP changes reflected the inhibition on the
      pyramidal tract during the 'No-go' session.

PMID- 8861115
TI  - Lateral suprasylvian visual cortex is activated earlier than or synchronously
      with primary visual cortex in the cat.
AB  - To explore functional connectivity between area 17 and posteromedial lateral
      suprasylvian (PMLS) area of the cat cerebral cortex, we carried out cross
      correlation analysis of spike trains of neurons recorded simultaneously from both
      areas of anesthetized, paralyzed cat. Most of correlated pairs had peaks which
      indicate that PMLS cells were activated earlier than or simultaneously with their
      partners in area 17, suggesting that 'backward' as well as synchronous activation
      operates between these cortical areas.

PMID- 8861116
TI  - Women's health and psychosomatic medicine.

PMID- 8861117
TI  - Sleep in women.

PMID- 8861118
TI  - Eating disorders associated with hyperemesis gravidarum.

PMID- 8861119
TI  - Miscarriage as a traumatic event: a review of the literature and new implications
      for intervention.
AB  - This review considers the psychological impact of miscarriage and follow-up care.
      A fifth of pregnancies end in miscarriage, and the experience leads to emotional
      consequences such as depression and anxiety, which may last for several months.
      Some have explored the focus of psychological morbidity and attempted to discover
      predictors of adjustment, but results are inconclusive. Grief has been identified
      as a feature of postmiscarriage distress, but trauma associated with the process
      of miscarriage has been neglected. Despite the recognized impact, there is
      dissatisfaction with professional emotional care, and there is no routine follow
      up. There have been no controlled intervention studies with women who miscarry
      during early pregnancy, although anecdotal evidence suggests beneficial effects.
      Such studied have concentrated on loss, but perhaps future research should
      consider the whole experience of miscarriage. An intervention derived from trauma
      research has been suggested as a possible strategy for facilitating emotional
      adjustment and preventing longer term negative responses.

PMID- 8861120
TI  - Similarities and differences in couples' grief reactions following a miscarriage:
      results from a longitudinal study.
AB  - Recent studies have documented grief and depressive reactions in women after a
      miscarriage. However, the men's reactions to their partner's experience have been
      neglected. In a controlled follow-up study, 56 couples were studied shortly after
      the miscarriage, and 6 (N = 47) and 12 months later (N = 45). The participants
      completed standardized questionnaires for depression, physical complaints,
      anxiety, and grief. Contrary to commonly held beliefs, men do grieve, but less
      intensely and enduringly than their partners. The manner in which they experience
      their grief is similar to that of the women, except that the men cry less and
      feel less need to talk about it. Unlike the women they do not react with an
      increased depressive reaction (compared to age- and sex-matched community control
      groups). Giving up their personal expectations, hopes for, and fantasies about
      the unborn child is a major source of grieving for both. Some men feel burdened
      by their wives' grief or depressive reactions. Conflicting reactions may affect
      the couples' interactions and promote depressive reactions in the women.

PMID- 8861121
TI  - Are coping strategies related to disease outcome in early breast cancer?
AB  - A consecutive series of 107 women with early breast cancer were investigated for
      coping strategies and disease outcome 5 to 6 years after primary surgical
      treatment (mastectomy or lumpectomy). Coping was assessed several times during a
      3-year investigation period by the Zurich and Freiburg Questionnaires of Coping
      with Illness (ZQCI, FQCI). Data analysis revealed no significant correlations
      between coping strategies and the target variable "death from breast cancer".
      However, significant relations were found between postsurgical tumour size (p <
      or = 0.01), positive histological node status (p < or = 0.01) and death from
      breast cancer. The results of a discriminant analysis also indicated that somatic
      parameters are more important for the course of breast cancer disease than
      psychological aspects of coping. The role of psychosocial variables for the
      outcome of cancer disease remains unclear and further studies in this field are
      necessary.

PMID- 8861122
TI  - Coping strategies and psychiatric morbidity in women attending breast assessment
      clinics.
AB  - This study examined the role of coping strategies and personality characteristics
      in mediating psychiatric morbidity in subjects facing possibly serious breast
      disease. Participating were 121 women aged 20 to 65 undergoing breast fine needle
      biopsy for a suspicious lesion on mammography. All subjects received psychosocial
      assessments including the 12-item General Health Questionnaire (GHQ-12), the
      Eysenck Personality Inventory (EPI) and the Coping Strategies Inventory. The
      results show that neuroticism was the only EPI subscore significantly correlated
      with GHQ-12 score. A habitual method of coping with adversity known as
      'engagement' has a negative correlation with GHQ-12 score; that is, patients who
      actively confront their illness and the uncertainty that surrounds it show better
      psychological health. Stepwise multiple regression reveals that neuroticism and
      an engagement coping strategy are the most significant predictors towards GHQ-12
      score prior to the diagnosis of breast cancer.

PMID- 8861123
TI  - Are multiple roles a risk factor for myocardial infarction in women?
AB  - This study examined whether multiple social roles are associated with an
      increased risk for a first myocardial infarction in a sample of Dutch women and
      whether there is evidence in favour of either the scarcity or the enhancement
      hypothesis about multiple roles. Subjects were 79 patients with a first
      myocardial infarction (MI), and they were compared with 90 hospital controls.
      Logistic regression analyses showed that multiple social roles do not constitute
      a risk factor for a first myocardial infarction. Classic risk factors seem to be
      more important. Neither the scarcity nor the enhancement hypothesis was confirmed
      in connection with a first myocardial infarction. However, the findings do
      support the enhancement hypothesis with regard to general health. In conclusion,
      the results indicate that multiple social roles do not constitute a risk factor
      for a first myocardial infarction in women.

PMID- 8861124
TI  - An evaluation of the efficacy of supervised cognitive behavioral self-help
      bulimia nervosa.
AB  - Eighty two patients with bulimia nervosa were managed by providing them with
      supervision in the use of a highly structured cognitive behavioral self-help
      manual. Their progress was assessed in an open clinical trial. The 67 patients
      who completed the course of self-help experienced considerable benefit; the
      frequency of bulimic episodes and self-induced vomiting decreasing by 80% and
      79%, respectively. Compared to those who benefited, those who had a poor outcome
      or dropped out of treatment were more than twice as likely to have had anorexia
      nervosa in the past and were somewhat more likely to have a personality disorder.
      Three-quarters of those who persisted with the programme of supervised self-help
      were followed up a year after commencing treatment. Clinical gains were well
      maintained: almost two thirds were abstinent with respect to both bulimic
      episodes and self-induced vomiting. It would seem appropriate that, as part of a
      stepped care approach to the management of bulimia nervosa, supervised cognitive
      behavioral self-help should routinely be the first line treatment.

PMID- 8861125
TI  - The hormonal response to intravenous 5-hydroxytryptophan in bulimia nervosa.
AB  - In recent years evidence has accumulated to implicate a disturbance in serotonin
      function in the eating disorder bulimia nervosa. This study employs a
      neuroendocrine technique to assess the effect of intravenous 5-hydroxytryptophan,
      the immediate precursor to serotonin, on peripheral hormones in bulimia nervosa
      subjects and controls. Blunted prolactin and growth hormone responses were
      observed among bulimia nervosa subjects; the possible pathophysiology and
      implications of the findings are discussed.

PMID- 8861126
TI  - Sexual behavior in pregnancy among Hong Kong Chinese women.
AB  - Sexual behavior during pregnancy was examined in a retrospective study of 150
      Hong Kong Chinese women interviewed in the immediate postpartum period. Sexual
      activity was found to decline abruptly during the first trimester of pregnancy,
      and continued to decrease in frequency as the pregnancy advanced. The frequency
      of intercourse was lower both before and during pregnancy than has been reported
      in similar studies among Western populations. There was no consistent
      relationship between age, parity, level of education, or employment status and
      sexual behavior either before or during pregnancy. These results suggest that a
      relatively conservative attitude toward sexual activity persists within this
      population.

PMID- 8861127
TI  - Psychosocial factors and chronic pelvic pain: a comparison of women with
      endometriosis and with unexplained pain.
AB  - Chronic pelvic pain is a common clinical problem, and physical investigation
      often fails to reveal its cause. For this reason, it has been argued that
      psychological and social factors contribute to such "unexplained" pain. Few
      studies to date using well-validated psychometric measures and adequate sample
      sizes have compared patients with unexplained pain and those with identified
      physical disease. The present study compared pain severity, mood symptoms,
      personality characteristics and social adjustment in women with unexplained pain
      and women with endometriosis. Women with endometriosis were more likely to come
      from upper socioeconomic groups. No differences in mood symptoms or personality
      characteristics were identified, but women with endometriosis had somewhat more
      severe pain and greater social dysfunction than those with unexplained pain. Mood
      disorder and social dysfunction appear to be at least as important in patients
      with proven endometriosis as in those with unexplained pain.

PMID- 8861128
TI  - Emotions and cognitions associated with bingeing and weight control behavior in
      bulimia.
AB  - The examination of cognitions and emotions during the bulimic cycle is critical
      in understanding possible maintenance factors involved in bulimia. In this study,
      22 bulimics and 22 nonbulimics recorded their thoughts and feelings every 2
      waking hours over a 6-day period. Bulimics additionally recorded their moods and
      thoughts during their binges and compensatory behaviors (e.g., purging,
      exercise). Higher levels of negative affect were reported at all stages of the
      cycle compared to baseline, although negative affect decreased after the
      compensatory behavior stage. Subjects also reported stronger distorted cognitions
      before and after the binge compared to baseline. One of the distorted cognitions
      (feeling fat) decreased in strength after subjects engaged in compensatory
      behavior. Additional analyses revealed that most levels of negative affect and
      distorted cognitions were elevated prior to binges as compared to meals. Finally,
      negative affect and distorted cognitions were stronger after binges than after
      meals.

PMID- 8861129
TI  - The relationship of childhood physical and sexual abuse to adult illness
      behavior.
AB  - A sample of 275 undergraduate subjects reported (i) their history of sexual and
      physical abuse in childhood and (ii) their health care utilization, somatization,
      and hypochondriasis as an adult. Physical and sexual abuse were recalled by
      largely separate groups, physical abuse predominating in males and sexual abuse
      in females. Both types of abuse were followed by a greater number of hospital
      admissions and surgical procedures in adulthood. Although sexual, and especially
      physical, abuse were associated with recall of emotionally disturbed parenting,
      this could not explain their influence on health care utilization because this
      was unrelated to parenting. Similarly, although abuse was followed by greater
      somatization and hypochondriasis, these also were unrelated to health care
      utilization. Physical and sexual abuse in childhood are risk factors, independent
      of their association with poor parenting, in the development of separate aspects
      of adult illness behavior.

PMID- 8861130
TI  - Effects of monovalent cations, pH and temperature on the dissociation constant
      (KD) for the fluorescent indicator mag-fura-2 at different excitation
      wavelengths.
AB  - The use of fluorescent indicators to quantify intracellular magnesium ([Mg(2+)]i)
      requires accurate determination of the dissociation constant (K(D)). Ideally, the
      K(D) should be determined intracellularly; however, in practice this is difficult
      to achieve. An alternative method is to measure the K(D) in solutions which
      attempt to mimic the intracellular milieu. This study investigated the effect of
      monovalent cations, pH and temperature on the Mg(2+)-mag-fura-2 K(D) determined
      at individual excitation wavelength intensities of either 340 nm or 380 nm, with
      emission fluorescence set at 510 nm. Monovalent cation concentration had little
      effect on K(D). Temperatures in the range 25 degrees C to 37 degrees C had
      significant effects on K(D) measured at 340 nm and 380 nm. At 340 nm the K(D)
      values at 25 degrees C and 37 degrees C were 2.02 and 1.15 mM, respectively and
      at 380 nm 2.84 to 1.68 mM, respectively. Changes of pH in the range 6.5 to 8.5
      had variable effects on the K(D) depending on the wavelength at which it was
      measured. The results illustrate not only how estimation of K(D) can vary with
      environmental conditions, including temperature and pH. but also the choice of
      wavelength.

PMID- 8861131
TI  - Mechanisms responsible for the increased magnesium efflux associated with raised
      [Na+]o in the isolated perfused rat heart.
AB  - The intracellular and extracellular concentration gradient of ionized magnesium
      (Mg(2+)) in the heart appears to be small, but large electrochemical gradients
      exist which will tend to move Mg(2+) into the cell. Since the myocardial plasma
      membrane is not impermeable to Mg(2+), mechanisms must exist to either inhibit
      influx or promote efflux of Mg(2+) in order to preserve steady state
      intracellular Mg(2+) concentration, [Mg(2+)]i. In this study the effects of
      extracellular sodium concentration ([Na+]o) on Mg(2+) transport were investigated
      in the isolated perfused rat heart. When [Na+]o was increased, using either
      sodium chloride (NaCl) or sodium isethionate (36.3 mM), a large Mg(2+) efflux and
      concomitant increase in the amplitude of contraction were observed. The raised
      NaCl-evoked Mg(2+) efflux was significantly inhibited by amiloride hydrochloride
      (10(-3) M and 10(-5) M) and by the beta-adrenergic antagonist, propranolol (10(
      5) M). Large Mg(2+) effluxes and concomitant increases in the amplitude of
      contraction were also observed during perfusion of the heart with choline
      chloride (36.3 mM) and sucrose (54.45 and 72.6 mM). The effect due to sucrose
      appeared to be concentration-dependent. Raised NaCl had no significant effect on
      lactate dehydrogenase activity. Although there seems to be an amiloride and
      propranolol sensitive component to Mg(2+)efflux in the mammalian heart, the
      changes in Mg(2+) efflux and contractile activity observed in these experiments
      may, to a large extent, be osmotic in origin.

PMID- 8861132
TI  - Uptake of (28)Mg by duodenal and jejunal brush border membrane vesicles in the
      rat.
AB  - Mg uptake was investigated with (28)Mg by a rapid filtration procedure in rat
      duodenal and jejunal brush border membrane (BBM) vesicles, prepared by CaCl(2)a
      or MgCl(2)b differential precipitation. At 1 mM Mg, 10 s uptakes were lower in
      jejunal vesicles (3.5(a) or 5.5(b) nmol/10 s per mg protein) than in duodenal
      vesicles (11.4(a) or 13.5(b) nmol/10 s per mg protein). The equilibrated 60 min
      uptakes were also lower in jejunum (11.0(a) or 26.6(b) nmol/60 min per mg
      protein) than in duodenum (l8.8(a) or 26.6(b) nmol/60 min per mg protein). The
      influence of medium osmolarity on 10s and 60 min uptakes of Mg indicated that Mg
      was 'transported' into osmotically active spaces. The effect of Mg concentration
      on the 10 s uptake suggested the existence of one single mechanism of transport
      in the duodenum, with an apparent K(T) of 1 mM, and of two mechanisms in the
      jejunum, with apparent K(T) values of 0.2 and 2-5 mM. Despite different amounts
      of calcium and magnesium in CaCl(2) and MgCl(2) precipitated vesicles, there were
      no large differences in magnesium uptakes depending on the mode of preparation of
      the vesicles. In contrast, calcium uptakes. measured with (45)Ca, were six to
      nine times higher in MgCl(2) prepared jejunal vesicles, and were always much
      higher than magnesium uptakes measured under the same conditions. At 0.1 mM
      calcium concentration, calcium uptake was depressed by 0.025 mM verapamil (50
      percent) and by 0.1 mM ZnCl(2)(40-75 percent), while Mg uptakes were unaffected.
      L-leucine or L-phenylalanine (5 mM), two inhibitors of intestinal alkaline
      phosphatase, decreased Mg uptake by 30 to 40 percent at 1 mM Mg, but had no
      significant effect at 0.1 mM, and did not affect calcium uptakes at all. A
      possible involvement of alkaline phosphatase in magnesium uptake was ascertained
      in jejunal BBM vesicles treated with phosphatidylinositol-specific phospholipase
      C, which partially released alkaline phosphatase from the BBM. Calcium uptakes
      were unaffected by the treatment, while magnesium uptakes were significantly
      decreased at 1 mM Mg. These results confirm that magnesium and calcium are
      transported by distinct mechanisms in the jejunum.

PMID- 8861133
TI  - Characterization of two mechanisms of (28)Mg uptake in rat jejunal brush border
      membrane vesicles.
AB  - Uptakes of (28)Mg at 10 s were measured at 0.1 and 1mM MgCl(2), to mainly
      represent one or other of the two uptake mechanisms earlier shown to be present
      in rat jejunal brush border membrane vesicles, one with an apparent KT of 0.2 mM,
      the other in the millimolar range. Both mechanisms had an optimal temperature
      close to 28 degrees C, inactivation at 37 degrees C being more acute for the low
      affinity mechanism (55 percent, P < 0.01). Both mechanisms were equally
      stimulated by an electrical potential difference (negative inside the vesicles)
      imposed by a potassium gradient and not affected by the nature of the anion
      accompanying magnesium. At 0.1 mM MgCl(2), the uptake was increased by an
      outwardly directed proton gradient, pH 8.2 outside and 7.4 inside (38 percent, P
      < 0.05), but not depressed when the gradient was in the opposite direction, pH
      6.6 outside and 7.4 inside. It was trans-stimulated by magnesium, strongly
      inhibited by amiloride and to a smaller extent by furosemide, but uninfluenced by
      0.1 mM NaCl or by 100 mM NaCl, NaSCN or KCl. A slight but significant inhibition
      (20-30 per cent) was recorded in the presence of 0.1 mM CoCl(2), NlCl(2) or
      BaCl(2). At 1 mM MgCl(2), the uptake was not influenced by pH gradient, was not
      trans-stimulated by Mg and was not affected by furosemide. A 40 percent
      inhibition by amiloride was, however, recorded. Also 100 mM NaCl or KCl doubled
      the uptake, while 1 mM NaCl or 100 mM NaSCN did not affect it. In contrast, all
      the divalent cations tested produced an inhibition (from 60 to 12 percent) in the
      following order: Co > or = Mn > Ca > or = Ni> Ba > Sr, when used at the same
      concentration as magnesium. The results showed that cobalt and calcium were not
      true competitors. In conclusion, two distinct mechanisms would operate magnesium
      entry at the brush border: (1) an electrogenic high affinity Mg/Mg,H exchange,
      sensitive to amiloride and furosemide, and (2) an electrogenic low affinity
      mechanism, inhibited by the presence of several divalent cations and dependent on
      the presence or activity of alkaline phosphatase.

PMID- 8861134
TI  - Quantitative analysis of EEG effects following experimental marginal magnesium
      and boron deprivation.
AB  - Magnesium (115 and 315 mg/d) and boron (0.23 and 3.23 mg/d) were fed in a double
      blind Latin squares design to 13 healthy postmenopausal women (aged 50-78 years)
      living on a metabolic unit. An eight-channel electroencephalogram (EEG) was
      recorded during the last week of each of four 6-week dietary periods. Power and
      coherence measures were determined for each of four EEG frequency bands: delta (1
      3 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (13-18 Hz). Compared to high
      dietary magnesium, the low magnesium intake increased total power in the frontal
      regions and right temporal and parietal regions and resulted in frequency
      specific increases in left occipital delta power, theta power in all but the left
      temporal region, alpha power in the right frontal and right temporal regions, and
      beta power in the frontal regions. The proportion of theta to total power in the
      parietal regions also increased with the low magnesium intake. While magnesium
      effects were observed primarily during eyes-closed conditions, effects of dietary
      boron on EEG power were found only during eyes-open conditions. Relative to high
      dietary boron, the low boron intake increased delta power in the left parietal
      and left occipital regions, increased the proportion of delta to total power in
      the frontal regions, and decreased relative right frontal theta, right frontal
      alpha, and left frontal beta power. Additional magnesium and boron effects were
      evident in the measures of EEG coherence. Thus relatively short periods of
      marginal magnesium and boron deprivation can affect brain function in healthy
      older women. The findings extend previous qualitative observations of increased
      CNS activity following severe magnesium deprivation and deficiency to cases of
      experimentally induced marginal magnesium deficiency, and verify CNS
      hyperexcitability by quantitative analysis of the EEG.

PMID- 8861135
TI  - Magnesium transport induced ex vivo by a pharmacological dose of insulin is
      impaired in non-insulin-dependent diabetes mellitus.
AB  - Diabetes mellitus may be associated with magnesium depletion, which in turn may
      contribute to metabolic complications of diabetes including vascular disease and
      osteoporosis. Intracellular depletion is thought to be due to osmotically induced
      renal magnesium loss; however, impaired ability of insulin to increase
      intracellular magnesium during insulin deficiency or insulin resistance could
      also play a role. Magnesium deficiency per se has also been reported to result in
      insulin resistance. In order to determine if magnesium transport is altered in
      non-insulin-dependent diabetes mellitus (NIDDM), we measured intracellular Mg(2+)
      in circulating lymphocytes obtained from nine normal subjects and seven patients
      with NIDDM. Ionized intracellular Mg(2+) was determined by fluorescent
      spectroscopy using Mg-fura-2. A 30 min incubation of insulin with lymphocytes
      obtained from normal subjects resulted in an increase in Mg(2+) of 8.6 +/- 3.6
      percent (mean +/- SEM) at 100 mu U/ml which reached a plateau at approximately
      250 mu U/ml (11.0 +/- 1.7 percent). The mean lymphocyte Mg(2+) in the patients
      (0.198 +/- 0.011 mM) was not significantly lower than normal (0.218 +/- 0.017).
      Insulin (500 mU/ml) added acutely during the fluorescence reading caused a rapid
      31 +/- 3.9 percent rise in intracellular Mg(2+) in the normal subjects, which was
      significantly greater than the 18 +/- 1.6 percent rise observed in the NIDDM
      subjects (P < 0.01). The effect of magnesium deficiency was also studied in 3
      normal subjects experimentally Mg deficient for 3 weeks. The mean lymphocyte
      Mg(2+) fell from 0.198 +/- 0.009 mM pre-diet to 0.153 +/- 0.006 mM post-diet. and
      the insulin-induced rise in Mg(2+) fell from 27.2 percent pre-magnesium depletion
      to 12.7 percent post-magnesium depletion. These data suggest that insulin
      resistance and magnesium depletion may result in a vicious cycle of worsening
      insulin resistance and decrease in intracellular Mg(2+) which may limit the role
      of magnesium in vital cellular processes.

PMID- 8861136
TI  - Variations of serum magnesium and zinc after surgery, and postoperative fatigue.
AB  - Changes in serum zinc and magnesium can be induced by stress from circumstances
      such as traumatic injury or inflammation. This present study involved 58 patients
      admitted for a variety of surgical abdominal interventions. After surgery, serum
      magnesium showed a minor increase on d 3 and d 9 (P < 0.05) and a return to
      initial levels on d 27 and d 45 after surgery. On the ninth postoperative day
      there was a significant decrease in serum zinc. On d 45, serum zinc
      concentrations increased to normal values. There was an inverse correlation
      between serum and dynamometric variables and fatigue. The relation between serum
      magnesium and zinc was in agreement with other studies; these changes might be
      due, at least in part, to stress. Surgical trauma increases corticosteroids,
      which affect the homeostasis of magnesium and zinc. In conclusion, increases in
      fatigue were accompanied by decreases in serum zinc and increases of serum
      magnesium. This suggests that these elements are implicated, directly or
      indirectly, in fatigue mechanisms, and therefore their measurement may be used as
      a guide to the status of fatigue in patients after surgery.

PMID- 8861137
TI  - Experimental and clinical effects of magnesium infusion in the treatment of
      neonatal pulmonary hypertension.
AB  - The appropriate treatment of persistent pulmonary hypertension of the newborn has
      led to the search for a specific pulmonary vasodilator. Persistent pulmonary
      hypertension of the newborn is characterized by a high pulmonary vascular
      resistance resulting in right to left shunting across the fetal channels. The
      ratio of pulmonary vascular resistance to systemic vascular resistance determines
      the magnitude of this shunt, and agents which lower both pulmonary and systemic
      blood pressure do not alleviate the right to left intracardiac shunt. Numerous
      vasodilator agents,including tolazoline, prostaglandins and nitrovasodilators,
      have been used but all have been associated with problematic falls in systemic
      blood pressure. Magnesium, called nature's calcium blocker, antagonizes calcium
      ion entry into smooth muscle cells, thus promoting vasodilatation. Magnesium is
      also a non-specific vasodilator,and while potentially lowering pulmonary vascular
      resistance, has been shown to cause a fall in systemic blood pressure in neonatal
      models of hypoxic or septic pulmonary hypertension. Case reports and a series of
      cases have noted beneficial effects in human newborns, which may have been due to
      other effects of magnesium (eg, sedation, muscle relaxation, bronchodilatation
      and cardioprotection). There are, however, no reported prospective randomized
      controlled trials of magnesium sulphate in human newborns with pulmonary
      hypertension. More recently, the discovery that inhaled nitric oxide acts as a
      specific pulmonary vasodilator without systemic side effects may reduce
      enthusiasm for the use of magnesium infusions in neonates with pulmonary
      hypertension. There appears to be sufficient evidence at present to justify a
      prospective randomized controlled trial to evaluate the role of magnesium
      infusion as a specific pulmonary vasodilator for the treatment of pulmonary
      hypertension in hypoxic human newborns.

PMID- 8861138
TI  - Antiarrhythmic action of pharmacological administration of magnesium in heart
      failure: a critical review of new data.
AB  - Congestive heart failure is characterized by contractile dysfunction and frequent
      complex ventricular ectopy. Despite advances in therapy, mortality from heart
      failure is substantial, estimated at 10-80 percent per year, and sudden death is
      common. Magnesium is the second most common intracellular cation, strongly
      influences cardiac cell membrane function, and is an important catalyst of many
      enzymatic reactions in the myocyte. Epidemiological studies have implicated
      magnesium deficit in the genesis of sudden death. Patients with congestive heart
      failure are predisposed to magnesium deficit for many reasons, including
      neurohormonal activation, poor gastrointestinal absorption, and drug therapy.
      Hypomagnesaemia is common in these patients and has been linked to an increased
      frequency of complex ventricular ectopy. Several early, uncontrolled studies have
      suggested a beneficial effect of magnesium administration on ventricular
      arrhythmias in patients with congestive heart failure. Two recent randomized,
      double blind, placebo-controlled trials have shown that both intravenous and oral
      administration of magnesium chloride results in a significant reduction in the
      frequency and complexity of ventricular arrhythmias in patients with congestive
      heart failure. Magnesium administration is well tolerated and serious adverse
      effects are rare. The potential mechanisms of the antiarrhythmic action of
      magnesium and limitations of the available data are discussed. The evidence
      reviewed suggests that serum magnesium concentrations should be monitored and
      corrected in patients with congestive heart failure. Ventricular arrhythmias may
      respond to acute intravenous magnesium administration, which should be considered
      as early therapy. Further study is needed to define magnesium dose and the effect
      of concomitant potassium administration. A prospective clinical trial is
      warranted to determine the chronic effects of magnesium administration in
      patients with heart failure.

PMID- 8861139
TI  - Commentary on recent clinical advances: magnesium depletion, magnesium deficiency
      and asthma.

PMID- 8861156
TI  - Disease cluster statistics for imprecise space-time locations.
AB  - Health professionals are investigating an increasing number of possible disease
      clusters, and statistical tests play an important role in cluster description and
      analysis. Existing cluster statistics assume precise data, when in reality health
      events are often imprecise (for example, place of residence is known only to the
      census district or zip code) and uncertain (for example, 'I first became ill
      sometime in 1985'). This incompatibility--precise methods used to analyse
      imprecise data--is largely ignored, resulting in test statistics of unknown
      accuracy. Most cluster statistics can be written as the cross-product of two
      matrices where one matrix reflects nearest-neighbour, distance or adjacency
      relationships and the second matrix is health related (for example, case-control
      identities). This paper explores a general approach to clustering, which
      incorporates uncertainty regarding space-time locations into these nearest
      neighbour, distance or adjacency relationships. Because the approach is general
      it can be used with almost all existing cluster tests, and, because it accounts
      for imprecise location data, it is suited to the 'real-world' nature of disease
      cluster investigations.

PMID- 8861157
TI  - The spatial autocorrelation coefficient Moran's I under heteroscedasticity.
AB  - The spatial distribution of rates used in epidemiology often raises questions
      concerning the randomness of the observed pattern. In order to provide a first
      answer to this kind of question, the well-known spatial autocorrelation
      coefficient Moran's I is frequently used. Unfortunately, under
      heteroscedasticity, that is, unequal variances of the rates due to different
      population sizes, the moments of the test distribution of Moran's I under H(0)
      differ from the usually used moments. To obtain a less biased test, it is
      proposed in this paper and validated by simulation results, to approximate the
      moments of Moran's I by means of incorporating population size into the
      covariance matrix of the rates.

PMID- 8861159
TI  - An introduction of smoothing incidence rates by penalized likelihood.
AB  - Most recent developments in the smoothing of disease incidence rates have
      involved empirical Bayes procedures. Through the introduction of an intersite
      distance penalty, the pooling of information by directly penalizing the maximum
      likelihood estimates is proposed. A distance type statistic tests a null
      hypothesis of homogeneity among the rates and is applied to gastric cancer
      incidence of Nova Scotia municipalities. For various spatial patterns, simulation
      results are presented which investigate the power of the test, the total mean
      squared error and the distribution of the smoothed estimates.

PMID- 8861158
TI  - Localization of disease clusters using regional measures of spatial
      autocorrelation.
AB  - Maps of disease rates are often used to identify regions with elevated disease
      rates. The goal of this study was to develop and evaluate a regional measure of
      spatial autocorrelation for localization of these clusters. A regional spatial
      autocorrelation coefficient (RSAC) was defined and a theoretical mean and
      standard deviation was derived for its probability distribution. The RSAC was
      used to identify spatial units that belong to disease clusters. The sensitivity
      and specificity of the RSAC method in detecting simulated disease clusters was
      evaluated. For comparison the simulated data were also used to evaluate methods
      employed by the National Cancer Institute (NCI) for mapping cancer mortality in
      the United States. The distribution of pancreatic cancer among the elderly white
      male population in the United States was also evaluated. Within a simulated
      disease cluster with a relative risk of 2, the RSAC method detected between 75
      per cent and 91 per cent of the units depending on the size of the spatial unit
      used for the analysis. The corresponding sensitivities of the NCI method ranged
      from 9 per cent to 68 per cent. The RSAC map of pancreatic cancer demonstrated an
      area of positive clustering (clustering of high rates) in the south central
      United States. The RSAC method localized disease clusters with greater
      sensitivity than the NCI method, particularly when geographic units were small.
      The RSAC method is an effective tool for the identification of regional disease
      clusters.

PMID- 8861160
TI  - Covariate adjusted mixture models and disease mapping with the program DismapWin.
AB  - The analysis and recognition of disease clustering in space and its
      representation on a map is an important problem in epidemiology. An approach
      using mixture models to identify spatial heterogeneity in disease risk and map
      construction within an empirical Bayes framework is described. Once heterogeneity
      is detected, the question arises as how explanatory variables could be included
      in the model. A mixed Poisson regression approach to include covariates is
      presented. The methods are illustrated using data for tuberculosis from Berlin in
      1991.

PMID- 8861161
TI  - The computer package DismapWin.

PMID- 8861162
TI  - Sorting variables for each case: a new algorithm to calculate injury severity
      score (ISS) using SPSS-PC.
AB  - One of the more often used measures of multiple injuries is the injury severity
      score (ISS). Determination of the ISS is based on the abbreviated injury scale
      (AIS). This paper suggests a new algorithm to sort the AISs for each case and
      calculate ISS. The program uses unsorted abbreviated injury scale (AIS) levels
      for each case and rearranges them in descending order. The first three sorted
      AISs representing the three most severe injuries of a person are then used to
      calculate injury severity score (ISS). This algorithm should be useful for
      analyses of clusters of injuries especially when more patients have multiple
      injuries.

PMID- 8861163
TI  - Quadrat analysis software for the detection of spatial or temporal clustering.
AB  - A software program is presented which automates the quadrat analysis procedure
      for detecting spatial or temporal clustering outlined by Boots and Getis. The
      software essentially compares observed values within areal or temporal sampling
      units to those values that would have been obtained were the values distributed
      randomly. A chi-square test of significance is used to assess whether the values
      are dispersed in a non-random pattern and a t-test is used to assess whether the
      values are dispersed in a non-regular pattern. The software requires DOS 3.3 or
      higher and reads dBase-compatible data files.

PMID- 8861164
TI  - Cluster: a software system for epidemiologic cluster analysis.
AB  - A software package for cluster analysis was developed that incorporates 12
      methods to analyse residence and time data, and morbidity or mortality rates. The
      Knox, Barton, Chen and Ohno methods of the software are illustrated with data for
      123 cancer cases reported by a citizen requesting a cluster investigation.
      Longitude and latitude for each address were assigned by a geographic information
      system for analyses with the Barton (p > 0.05) and Knox methods (p > 0.05). The
      data were also analysed for time of the event with the Chen method, comparing the
      observed incidence to expected county disease rates (p = 0.61), and for temporal
      patterns within the geographically defined population with the Ohno method (p
      >0.05). It was concluded that no statistically significant disease cluster
      existed.

PMID- 8861165
TI  - Statistical software for the clustering of health events.

PMID- 8861166
TI  - The pop-out of Hathor.

PMID- 8861167
TI  - Rotation and radical motion thresholds support a two-stage model of differential
      motion analysis.
AB  - Lower motion thresholds for rotational and radial flow have been measured for
      stimuli consisting of four closely packed circular apertures, each containing
      patches of drifting grating or plaid. Detection and direction thresholds were
      measured for gratings and plaids as a function of the relative orientation of the
      pattern components. There was a similarity between both types of threshold,
      supporting the existence of specialised rotation and radial-flow detectors.
      Further, thresholds increased with the relative component orientation for both
      gratings and plaids. This suggests that component information from a first stage,
      tuned spatiotemporally and to orientation, is being used directly to compute the
      optic flow in a two-stage process. A model based on this architecture is
      described by means of simple template receptive-field arrays with separable
      temporal and spatial tuning at the first stage.

PMID- 8861168
TI  - Depth judgments of triangular surfaces during moving monocular viewing.
AB  - When an observer judges the orientation in depth of a trapezoidal surface, the
      pictorial information of the surface is often more influential than motion
      information. Motion information might be more effective if pictorial information
      is simplified: this prompts the present study. Surfaces were triangular and
      pictorial information resided only in the visual lengths of the surfaces. In
      experiment 1, monocular observers viewed during head motions of 0 to 30 cm
      extent. Static judgments were somewhat dependent on visual length and tended to
      be frontal. Contrary to predictions, moving judgments were similarly affected:
      only 30 cm motion elicited near-veridical perception, as in previous studies with
      trapezoidal surfaces, although visual length had a residual effect. Experiment 2
      involved investigation of whether visual length requires prior exposure to
      triangular surfaces to be effective; this was found not to be the case, which
      argues that observers rely on internal models of triangular surfaces. Depth
      perception appears to balance rapidity of processing against accuracy, in a way
      suggesting that 'direct' approaches are incomplete. Finally, it is argued that
      depth-from-motion simulations-influential in assertions that motion information
      is fully effective-depend on pictorial information.

PMID- 8861169
TI  - Perception and recognition of normal and negative faces: the role of shape from
      shading and pigmentation cues.
AB  - A face is surprisingly difficult to recognise when presented in photographic
      negative, and negation has also been shown to affect simple perceptual judgments
      about a face. Two possible explanations for this effect are examined. In the
      shape-from-shading explanation it is argued that negating an image results in an
      impossible pattern of shading, and that this disrupts the formation of a three
      dimensional representation of the surface geometry of the face. In an alternative
      account for this effect it is suggested that identification errors occur as a
      consequence of changes to the apparent pigmentation of the face caused by
      negating the image. Three experiments are reported which are designed to test
      these explanations by using novel colour-image transformations in which the hue
      and luminance components of images are independently manipulated. The results of
      these studies suggest that although changes to the apparent pigmentation of a
      face might result in identification errors in some situations, the loss of shape
      from-shading cues is a more important cause of the negation effect. The role of
      these two sources of information in the recognition of normal faces is also
      discussed.

PMID- 8861170
TI  - Decay and interference effects in visuospatial short-term memory.
AB  - The method of constant stimuli was used to examine the accuracy with which two
      dimensional spatial information can be represented in mental images. In
      experiment 1, subjects had to decide which of two successively presented two-dot
      separations was wider. Over the range of interstimulus intervals employed (0 to
      30s), there was a linear relationship between interstimulus interval and spatial
      interval thresholds. In experiment 2 subjects' abilities to represent accurately
      more than one spatial interval at a time was investigated. Three dot pairs were
      presented, but only two pairs were to be compared, the third being completely
      irrelevant to the task. This manipulation doubled thresholds (relative to a two
      dot-pair control condition), whether or not subjects were obliged to attend to
      the irrelevant dots. Overall, the results suggest that mental representations of
      spatial information may be temporally durable, but only in the absence of
      extraneous stimuli. The latter not only disrupt memory for spatial information,
      but appear to have obligatory access to it.

PMID- 8861171
TI  - Psychophysical evidence of a sustained input to directionally selective motion
      mechanisms.
AB  - Human psychophysical evidence congruent with neurophysiological findings of a
      sustained input to directionally selective motion sensors in cat visual cortex is
      reported. Apparent motion was produced by displaying a group of dots in two
      frames (F1 and F2), where F2 was a translated version of F1. All stimulus
      sequences included a period during which F1 and F2 were displayed concurrently
      (combined images) and a period during which only F1 or F2 was on display (single
      images). There were three stimulus sequences: a display beginning with combined
      and ending with single image, a display beginning with single and ending with
      combined image, and a display beginning with F1, continuing with combined image,
      and ending with F2. Six durations of single and of combined images (10, 20, 40,
      80, 160, and 320 ms) were crossed factorially in each stimulus sequence.
      Directional motion was seen easily at long durations of the single image in all
      stimulus sequences, as would be expected on the basis of a sustained input to the
      directional-motion-sensing mechanisms. Perception of directional motion improved
      with the duration of single images, but declined as the duration of combined
      images was increased. Baker and Cynader's model could account for the effect of
      duration of single images, but not for the effect of duration of combined images.
      An elaborated version of the model provides a good qualitative match to all
      empirical findings.

PMID- 8861172
TI  - The half-Zollner illusion.
AB  - The Zollner figure contains stacks of short parallel segments oriented obliquely
      to the direction of the stack. Adjacent parallel stacks of opposite polarity seem
      to diverge where their top segments form an arrowhead. To probe whether or not
      the opposite polarities are necessary to the illusion, three 'half-Zollner'
      configurations were designed, containing stacks of a single polarity. The
      'orientation profile' of these configurations was studied, that is, the way the
      strength of the perceived illusion varies with the orientation of the stacks. The
      subjects had to align two stacks or align stacks with target segments situated at
      a slight distance from them. All three half-Zollner configurations produced
      errors that could be assimilated to global-orientation misjudgments. These errors
      were of opposite sign for the two types of stacks and varied with the orientation
      of the stacks as in the standard Zollner illusion. A further study was conducted
      in which the effect of several configurational parameters was explored for a
      single observer. The standard Zollner illusion increases with the separation of
      the stacks. The illusion is also increased when the orientations of the segments
      in different stacks are orthogonal, independently of the particular longitudinal
      orientations of the stacks. When the ends of the short segments are curved so
      that at their endpoints they become precisely perpendicular to the axis of the
      stacks, the standard and half-Zollner illusions are reduced, but not abolished.
      Therefore, they cannot be entirely accounted for by a mechanism of alignment of
      illusory contours generated at these endpoints. The results are consistent with
      the existence of a single common mechanism at work in both the standard and the
      half-Zollner illusion. It is suggested that the illusion itself is not a rotation
      of the stacks but either a shear deformation in which the segments of a stack
      slide with respect to one another, or an expansion of the stacks orthogonally to
      the segments.

PMID- 8861173
TI  - Categorical local-shape perception.
AB  - How well do observers perceive the local shape of an object from its shaded
      image? This problem was addressed by first deriving a potential representation of
      local solid shape. The descriptor of local shape, called shape characteristic,
      provides a viewpoint-independent continuum between hyperbolic (saddle-shaped) and
      elliptic (egg-shaped) points. The ability of human observers to make categorical
      judgments of local solid shape was then studied. This question was investigated
      by using a smooth 'croissant', a simple object made of two connected regions of
      elliptic and hyperbolic points. Observers decided whether the surface was locally
      elliptic or hyperbolic at various points on the object. The task was natural, and
      the observers could reliably partition the shaded image of the object into two
      regions, one elliptic and one hyperbolic. The ability of observers to perform
      this partition shows that they can, at least implicitly, localize the parabolic
      curves on a surface. This ability to locate the parabolic curve could in turn be
      exploited for other purposes, for instance to segment an object into its parts.

PMID- 8861174
TI  - Haptic aftereffect of curved surfaces.
AB  - A haptic aftereffect of curved surfaces is demonstrated. Two spherical surfaces
      were presented sequentially to human subjects. They rested one hand on the first
      (conditioning) surface. After a fixed conditioning period they transferred their
      hand to the second (test) surface and judged whether the test surface was convex
      or concave. In experiment 1 the curvature of the conditioning surface was varied;
      the subject's judgment of convexity or concavity of the test surface was strongly
      shifted in the direction opposite to the curvature of the conditioning surface
      (negative aftereffect). Therefore, subjects judged a flat surface to be concave
      after being exposed to a convex surface. After a conditioning period of 5 s the
      shift was about 20% of the curvature of the conditioning surface. In experiment 2
      the duration of the conditioning period was varied; the magnitude of the
      aftereffect could be described by a first-order integrator with a time constant
      of 2 s. In experiment 3 the time interval between the conditioning period and the
      touching of the second surface was varied; the magnitude of the aftereffect could
      be described by an exponential decay with a time constant of 40 s. It is
      concluded that the haptic aftereffect of curved surfaces is an important effect
      that occurs almost instantaneously and lasts for an appreciable period.

PMID- 8861175
TI  - Possible involvement of an endogenous benzodiazepine receptor ligand of the
      inverse agonist type in the regulation of rapid-eye movement (REM) sleep: an
      hypothesis.
AB  - 1. Rapid-eye movement (REM) sleep is a complex behavioral state characterized by
      desynchronized electroencephalographic (EEG) activity, postural atonia, rapid,
      saccadic movements of the eyes, and vivid dreaming. 2. A recently developed class
      of drugs, the inverse agonist beta-carboline-3-carboxylates, elicits a number of
      effects similar to the properties of REM sleep, such as desynchronized cortical
      EEG and penile erections. 3. The hypothesis is put forth that an endogenous beta
      carboline-3-carboxylate exists which may initiate many aspects of REM sleep. 4.
      Clinical relevance of this hypothesis is discussed with regard to REM anxiety
      dreams, night terrors, narcolepsy, and depression.

PMID- 8861176
TI  - Platelet [3H]dopamine uptake is differentially affected by neuroleptic drug
      treatment in schizophrenia and schizophreniform disorder.
AB  - 1. The uptake of [3H] dopamine was measured using platelet-rich plasma (PRP) from
      neuroleptic-free subjects and again, in some cases, after the subject had been
      treated with neuroleptic drugs. 2. There were no differences in [3H]dopamine
      uptake by PRP in subjects who were or were not mentally ill. 3. After treatment
      with neuroleptic drugs the Km for platelet [3H] dopamine uptake had increased in
      76% of subjects with schizophrenia and 87% of subjects with schizophreniform
      disorder. Similarly, the Vmax for platelet [3H]dopamine uptake had increased in
      81% of the subjects with schizophrenia and 86% of the subjects with
      schizophreniform disorder. 4. By contrast, the Km for platelet [3H]dopamine
      uptake had decreased in 94% of subjects who had a psychoses associated with an
      illness other than schizophrenia or schizophreniform-disorder whilst the Vmax for
      platelet [3H]dopamine uptake also decreased by 94% in these subjects. 5. In
      subjects with psychoses, platelet [(3)H] dopamine uptake is differentially
      altered during neuroleptic drug treatment depending on diagnosis.

PMID- 8861178
TI  - Haloperidol and reduced haloperidol plasma concentrations after a loading dose
      regimen with haloperidol decanoate.
AB  - 1. Haloperidol and reduced haloperidol plasma levels were measured in
      schizophrenic patients who received both oral (10 mg, N=16 and 20 mg, N=4) and
      depot haloperidol treatment 2. Patients were of Asian ethnicity and were safely
      and effectively converted from oral to depot therapy using a loading dose regimen
      using a 100 mg weekly injection interval for 4 weeks, biweekly for one month and
      then monthly. 3. Significant correlations were found for plasma haloperidol and
      reduced haloperidol levels and reduced haloperidol/haloperidol ratios between
      oral and depot therapy in these non-smoking patients. 4. A loading dose regimen
      is needed due to the long elimination half-life of decanoate of 26 days otherwise
      steady-state condition will not occur until 34 months of therapy. 5. Patients
      were maintained on monthly depot treatment for 40 weeks after the loading dose
      regimen and only one patient relapsed during treatment despite dosage increases.
      6. The formation of reduced haloperidol remained consistent for oral and depot
      haloperidol treatment.

PMID- 8861177
TI  - A double-blind comparison of venlafaxine and fluoxetine for treatment of major
      depression in outpatients.
AB  - 1. This was a randomized, double-blind comparison of the efficacy and safety of
      venlafaxine and fluoxetine in outpatients with major depression. 2. Three hundred
      fourteen patients were randomly assigned to either venlafaxine 37.5 mg twice
      daily or fluoxetine 20 mg once daily for a maximum of 8 weeks. 3. If the response
      was inadequate after two weeks of treatment, the dosage of venlafaxine could be
      increased to 75 mg twice daily. 4. A clinical response, defined as at least a 50%
      decrease from baseline in the total HAM-D score, was attained at week 6 in 72% of
      patients on venlafaxine and 60% of patients on fluoxetine (p = 0.023). 5. Among
      patients who increased their dose at 2 weeks, venlafaxine was significantly (p <
      0.05) superior from week 3 onward on the HAM-D. 6. Venlafaxine 75 mg daily is
      comparable to fluoxetine, but at 150 mg daily, it may be superior to fluoxetine
      in outpatients with major depression who do not respond early to treatment.

PMID- 8861179
TI  - Lithium side effects in relation to brain lithium concentration measured by
      lithium-7 magnetic resonance spectroscopy.
AB  - 1. The relationship between lithium (Li) side effects and brain Li concentration
      was examined in 17 patients with bipolar disorder treated with Li and other
      psychotropic drugs. 2. Brain Li concentration was measured by Li-7 magnetic
      resonance spectroscopy (MRS). Side effects were assessed using the UCLA General
      Side Effect Rating Scale For Lithium Treatment (GSE). 3. There was no correlation
      between the total GSE score and the brain, serum, or erythrocyte Li
      concentrations. Patients with hand tremor had significantly higher brain Li level
      (0.51 + or - 0.27 mM) than those without apparent tremor (0.36 + or - 0.20 mM),
      but no significant difference in serum Li level was seen. As far as the patients
      had hand tremor, they rarely had brain Li concentration less than the therapeutic
      range (1 of 15 measurement). On the other hand, they often had brain Li levels
      less than the therapeutic range when they did not have apparent tremor (13 of 52
      measurements). 4. This preliminary study suggests that hand tremor is associated
      with the brain Li concentration.

PMID- 8861180
TI  - Evaluation of cyclic AMP accumulation in EBV-transformed human B-lymphocytes:
      effects of dopamine agonists, isoproterenol, prostaglandin E1, cholera toxin,
      forskolin, and phorbol 12-myristate-13 acetate.
AB  - 1. Phorbol 12-myristate-13-acetate (PMA), a protein kinase C activator, elevated
      cyclic AMP accumulation in EBV-transformed human B-lymphocytes, and potentiated
      isoproterenol-, prostaglandin- (PGE1), cholera toxin-, and forskolin-stimulated
      cyclic AMP accumulation. 2. The dopamine D1 receptor agonist, SKF38393 (10(-7) to
      10(-5) MH, had no effect on cyclic AMP accumulation in transformed human B
      lymphocytes. 3. The dopamine D2 receptor agonist, quinpirole (10(-7) to 10(-5) MH
      did not inhibit cyclic AMP accumulation even when cyclic AMP accumulation was
      maximized by the addition of PMA and forskolin. 4. These data suggest that
      dopamine D1- and D2-receptor coupling to a cyclic AMP generating system is not
      present at detectable levels in transformed human B-lymphocytes.

PMID- 8861181
TI  - The neurochemical effects on striatal dopamine turnover rate of N-stearyl
      dopamine after acute administration in rats.
AB  - 1. Considerable efforts have been made in order to develop autoreceptor selective
      agonists for the treatment of schizophrenia and hyperkinetic disorders. 2. Recent
      behavioural studies showed that the newly synthesized dopamine lipoamide, N
      stearyl dopamine induced a strong hypomotility (-80%) in rats and mice. It is
      worth noting that this behavioural response was partially antagonized by
      dopaminergic antagonists, such as haloperidol and sulpiride, administered at
      doses that block DA autoreceptors. 3. In the present study the authors
      investigated the neurochemical changes induced by S-DA, in the striatum of the
      rat brain, in order to estimate a possible correlation between the above
      mentioned behavioural response and DA metabolism. 4. S-DA (10 or 100 mg/kg, i.p.)
      induced a significant decrease in DA turnover rate while it did not affect 5-HT
      metabolism in the striatum. 5. Considering that 5-DA induces a strong
      hypomotility, which can be partially antagonized by haloperidol or sulpiride
      administered at low doses, while also decreases the striatal DA turnover rate, it
      could be suggested that together these findings indicate that this DA lipoamide
      may be display the characteristics of an antipsychotic agent, acting on the "DA
      selective" autoreceptors.

PMID- 8861182
TI  - Chronic nimodipine and yawning behavior in grouped or individually housed rats.
AB  - 1. The effects of a chronic administration (around 30 mg/ kg/day) of the
      dihydropyridine calcium antagonist nimodipine, on apomorphine induced yawning
      behaviour of grouped or individual housed rats, were studied. 2. Nimodipine
      treatment had no effect in grouped rats. 3. Individually housed animals gave a
      significant lower number of yawns in respect to grouped controls: this difference
      disappeared in isolated, nimodipine treated, group. 4. The results show the
      ability of nimodipine to restore a depressed behavioural performance.

PMID- 8861183
TI  - Behavioral effects of HT-90B, a putative novel anxiolytic agent with potent
      antidepressive activity.
AB  - 1. HT-90B,((-)-N-[2-(8-methyl-1,4-benzodioxane-2-ylmethyl)am in
      o]ethyl]tricyclo[3,3,1,1(3,7)] decane-1-carboxamide), is a novel serotonin 5
      HT(1A) full agonist with serotonin 5-HT(2) antagonistic action. 2. In a water
      licking conflict test, HT-90B (3-30 mg/kg, po) was more effective than buspirone
      in abolishing response suppression. 3. In a forced swim test, HT-90B (3-30 mg/kg,
      po) reduced the duration of immobility after a single oral dose, which contrasts
      with the requirement of multiple doses for desipramine (as a standard
      antidepressant) to produce the effect. 4. These two behavioral effects of HT-90B
      (20 mg/kg,po) were still evident even 4 hr after oral administration. And no
      tolerance was observed for these behavioral effects after repeated oral
      administration (10 mg/kg, b.i.d., 2 weeks). 5. HT-90B hardly produced any
      diazepam- or buspirone-like side effects. 6. In conclusion, it is suggested HT
      90B is a potent anti-depressive anxiolytic with minimal side effects.

PMID- 8861184
TI  - Effects of acute and chronic administration of high-dose corticosterone and
      dexamethasone on regional brain dopamine and serotonin metabolism in rats.
AB  - 1. The effects of acute and chronic treatment with high-dose corticosterone (50
      mg/kg) and dexamethasone (0.7 mg/kg) on monoamines and their metabolites levels
      in four regions of the rat brain were investigated. 2. Acute corticosterone and
      dexamethasone treatment decreased serotonin (5-HT) levels, but did not alter
      dopamine (DA),3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or
      5-hydroxyindoleacetic acid (5-HIAA) levels in any of the brain regions. 3.
      Chronic corticosterone treatment significantly increased the HVA and 5-HIAA
      levels only in the medial prefrontal cortex, while chronic dexamethasone
      treatment did not alter. Chronic corticosterone and dexamethasone treatment did
      not change DA, DOPAC or 5-HT levels in any of the brain regions. 4. These
      findings suggest that chronic treatment with high-dose corticosterone activates
      the dopaminergic and serotonergic neurotransmission in the medial prefrontal
      cortex.

PMID- 8861185
TI  - Effect of citalopram on the desensitization of serotonin-2A receptor-mediated
      calcium mobilization in rat glioma cells.
AB  - 1. The authors have investigated the effect of citalopram, an effective
      antidepressant drug with selective serotonin (5-HT) uptake inhibition, on 5-HT-2A
      receptor-mediated intracellular calcium (Ca2+) rise in C6 cultured cells. 2.
      Citalopram, at concentrations of 10 and 30 mu M, did not significantly reduce the
      Ca2+ mobilization induced by 10 mu M 5-HT, indicating that citalopram has little
      affinity for 5-HT-2A receptors. 3. Citalopram did not alter a subsequent response
      to 5-HT after citalopram was pre-applied to the cells. 4. However, citalopram
      inhibited the desensitization of 5-HT-2A receptors. When the cells were
      pretreated with citalopram and 5-HT, the subsequent response to 5-HT was
      significantly greater than that obtained following pretreatment with 5-HT alone.
      5. To investigate the mechanism of action of citalopram on the desensitization of
      5-HT-2A receptors, NaF-induced cGMP generation was measured. Citalopram inhibited
      the generation of cGMP induced by NaF in C6 cells as well as W-7. 6. These
      results indicate that citalopram antagonized the desensitization of 5-HT-2A
      receptor-mediated Ca2+ mobilization and this antagonism may be mediated by a
      calmodulin-dependent pathway in C6 glioma cells.

PMID- 8861186
TI  - 2-buten 4 olide affects feeding behavior of rhesus monkey.
AB  - 1. Endogenous satiety substance 2-Buten 4 Olide (2-B40- a short chain sugar
      derivative) effect on feeding behaviour of rhesus monkey was studied. 2. The
      cannula was implanted in the third ventricle of three, adult, male, rhesus
      monkeys. 3. Monkeys were conditioned to ingest their daily requirement of food
      during one hour. 4. Their daily food intake was recorded. 5. Various doses of 2
      B40 (1.6, 2.1, 2.7, 4.3, 10.6, 20 and 25 mg)were administered
      intracerebroventricularly on different days five minutes prior to presentation of
      food. 6. The effective dose for inducing significant satiety effect was 20.0 mg,
      while 10.6 mg induced a mild and 25.0 mg a severe effect. 7.However, when
      administered intraperitoneally 43 mg/kg bw 2-B40 induced satiety effect, but was
      ineffective in doses of 1.5 to 21.5 mg bw. 8. This study is suggestive of the
      presence of 2-B40 satiety mechanism in monkeys almost in doses similar to those
      previously reported for rats.

PMID- 8861187
TI  - Acute brain syndrome after tapering off clozapine in clozapine-lithium
      combination.
AB  - 1. This is a report of a patient who developed an acute organic psychosis due to
      neurotoxicity of lithium several days after tapering off a long-lasting clozapine
      therapy. 2. The organic brain syndrome with initial illusionary misperceptions, a
      confusional state and a lapse into a pre-coma developed three days after the end
      of clozapine therapy and seven days after the beginning of haloperidol addition.
      3. Possible pharmacokinetic and pharmacodynamic factors responsible for the
      severe neurotoxicity of lithium after withdrawal of clozapine and addition of
      haloperidol are discussed.

PMID- 8861188
TI  - Predator-elicited flight responses in Swiss-Webster mice: an experimental model
      of panic attacks.
AB  - 1. The nosological status of panic disorder is still a matter of debate.
      Nevertheless, evidence is emerging that panic attacks have a different pattern of
      drug responsiveness from other forms of anxiety. 2. Several experimental animal
      models of panic attacks have been developed. These vary in the extent to which
      they meet criteria for face validity, predictive validity and construct validity,
      normally applied to such models. 3. In the present review, the authors examine
      the possibility that predator-elicited flight responses in Swiss-Webster mice
      might serve as an experimental model for the screening of panic-modulating drugs.
      4. Drug effects on flight responses clearly indicate that this model has good
      predictive validity as panic-promoting agents increase flight reactions, while
      panicolytic drug challenge induces opposite effects. In addition, drugs devoid of
      any effect on panic attack, also do not alter flight behavior. 5. These findings
      strongly suggest that the model of predator-elicited flight responses in Swiss
      Webster mice is useful for the investigation of panic-modulating drugs.

PMID- 8861189
TI  - Neurobiological and psychopharmacological basis in the therapy of bulimia and
      anorexia.
AB  - 1. Eating disorders can be found in several psychiatric pathologies:
      schizophrenia, delusional disorder (somatic type), bipolar disorders, major
      depressive disorder, borderline personality disorder, generalized anxiety
      disorder, body dysmorphic disorder, somatization disorder and conversion
      disorder. 2. Although their clinical features have been defined, relatively
      little is known about the role of neurobiological patterns in the pathogenesis of
      these disorders. Several CNS neurotransmitters and neuromodulators are involved
      in the regulation of eating behavior in animals and have been implicated in
      symptoms such as depression and anxiety often observed in patients with eating
      disorders. The authors will review some studies on NA, DA, 5-HT, beta-endorphins,
      CRH, VP, OT, CCK, NPY and PYY involved in eating disorders. Furthermore, we will
      highlight some of the studies on drug therapy of eating disorders taking into
      account the effects of these agents on neurotransmitters and neuromodulators. 3.
      Antidepressant drugs have long been used for anorexia nervosa and bulimia, these
      disorders been claimed to be affective equivalent. Antidepressant agents seem to
      be effective in reducing the frequency of binge-eating episodes, purging behavior
      and depressive symptomatology. It is notable that antidepressant agents have been
      proved to be effective in patients with chronic bulimic symptoms, even in cases
      persisting for many years and in patients who had repeatedly failed courses of
      alternative therapeutic approaches. In all of the positive studies,
      antidepressant agents appeared effective even in bulimic subjects who did not
      display concomitant depression. 4. Few controlled studies on use of medications
      for anorexia nervosa have been published. Central serotonergic receptor-blocking
      compounds such as cyproheptadine cause marked increase in appetite and body
      weight. Zinc supplementation or cisapride could be a therapeutic option in
      addition to psychological and other approaches in anorexia nervosa. 5. There is
      no therapy as yet which is fully effective in alimentary disorders. Psychotropic
      drugs give some relief from symptoms, but they cannot cure the disorders. An
      integrated approach, either pharmacological or psychological, is still
      recommendable.

PMID- 8861190
TI  - Season of birth and schizophrenia: sex difference.
AB  - 1. A statistically significant increased risk of schizophrenia for individuals
      born in winter has been reported. The increase risk is of the order of 5-15
      percent. The seasonal effect is more marked among females. This winter birth
      effect suggests some environmental agents, probably a neuropathogen one, acting
      on the foetus. 2. The present study sought to test the environmental damage
      hypothesis by application of the family history of psychiatric disorder
      distinction to season of birth data divided according to sex and using a control
      population. 3. From computer records, all patients admitted to the psychiatric
      department of Marseilles Timone hospital between January 1984 and December 1989
      who satisfied DSM III, DSM III R criteria for schizophrenia were identified.
      Patients were then classified into two groups: family history of psychiatric
      disorder versus no family history. Division according to the sex was carried on
      after two groups were formed. 4. The data show (I) a significant excess of births
      in the early months of the year (p < 0.05) for all patients with no family
      history of psychiatric disorder, (2) a significant excess of births for females
      (p < 0.05) with no family history. 5. These results provide indirect support for
      the neurodevelopmental theory of schizophrenia.

PMID- 8861191
TI  - Increased pupillary sensitivity to pilocarpine in depression.
AB  - 1. The present study was undertaken to examine the hypothesis that muscarinic
      receptor sensitivity is increased in depression. 2. Pupillary responses to
      increasing concentrations of pilocarpine (O.08%-O.23%) given in a 2 ml solution
      were compared between ten male patients with major depression and a matched group
      of normal controls. 3. Individual differences in pupil size due to anatomic
      variability or adrenergic tone were evaluated under conditions of maximum pupil
      dilation following cholinergic blockade (tropicamide, 0.5 percent). 4. In
      contrast to controls, depressed patients exhibited significantly greater
      reductions in pupillary diameter following pilocarpine in doses between 0.095%
      0.185%. This was true regardless of whether or not the results were adjusted for
      differences in dilated pupil size. 5. These results are consistent with the idea
      that muscarinic sensitivity is increased in depression and indicate that
      depressed patients may be discriminated from controls on the basis of pupillary
      sensitivity to pilocarpine.

PMID- 8861192
TI  - Use of clozapine in tardive dystonia.
AB  - 1. This open clinical trial (N = 7) measured the course of severe tardive
      dystonia in chronic psychiatric patients after discontinuation of neuroleptics
      and subsequent use of clozapine. 2. The dystonia was regularly assessed using the
      Fahn-Marsden Rating Scale. The eventual concomitant tardive dyskinesia was
      assessed using the Abnormal Involuntary Movement Scale. The mean follow up was
      103 weeks. 3. The results for the tardive dystonia: four patients recovered
      totally, two improved considerably and one did not recover. 4. The results for
      the concomitant tardive dyskinesia: five of the seven patients had also
      dyskinesia, one patient had a total, two a partly remission, one had a very
      fluctuating course, and one patient worsened. Another patient developed
      dyskinesia. 5. It is suggested to consider clozapine for patients with tardive
      dystonia who have to continue antipsychotic treatment.

PMID- 8861193
TI  - Maintenance of muscimol-induced long-term depression by neurosteroids.
AB  - 1. The present study was undertaken to expand investigations of the interaction
      between neurosteroids and long-term depression (LTD) induced by muscimol 10 mu M.
      2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat
      hippocampal slices following orthodromic stimulation of Schaffer collateral
      fibres in stratum radiatum (0.01 Hz) 3. As previously reported, muscimol at 10 mu
      M induced a time, frequency of stimulation and concentration-dependent LTD of the
      amplitude of orthodromic potentials. Alphaxalone, at concentrations that had no
      significant effect themselves on the population spike (0.5 and 1 mu M)
      potentiated the inhibitory effect of muscimol on the population spike size. 4. It
      is now reported that low concentrations of alphaxalone are able to potentiate the
      ability of muscimol to induce LTD. In addition, concentrations of muscimol as low
      as 1 mu M which are not themselves able to induce LTD, as well as aiphaxalone and
      5 alpha-pregnan-3 alpha-ol-20-one 1 mu M were able to maintain the LTD induced by
      muscimol 10 mu M 5. It is suggested that the ability of such low concentrations
      of GABA receptor agonists to maintain LTD could be of physiological importance.

PMID- 8861194
TI  - Simultaneous monitoring of dopamine, its metabolites and trans-isomer of atypical
      neuroleptic drug carbidine concentrations in striatal dialysates of conscious
      rats.
AB  - 1. Transcerebral microdialysis was used to monitor dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and trans-isomer of
      atypical neuroleptic drug carbidine concentrations in the dialysates from dorsal
      striatum of freely moving rats following i.p. administration of the drug at doses
      0.5, 1,5 and 25 mg/kg. The changes in locomotor activity as well as catalepsy in
      rats following transcarbidine administration were also evaluated. 2. The
      microdialysis "point of no net flux" method was used to measure interstitial free
      concentration (IFC) of trans-carbidine in the dorsal striatum of freely moving
      rats following i.p. administration of the drug at dose 5 mg/kg. The maximal IFC
      of trans-carbidine was found to be approximately 1 mu M 20-40 min after
      injection. 3. The drug at doses up to 1 mg/kg produces elevation of dopamine
      release not affecting sufficiently its metabolite dialysate levels. IFC of the
      drug calculated for these doses will not exceed 0.24 pM. At the dose 5 mg/kg,
      i.p., elevation of both dopamine release and metabolism was observed and dopamine
      release increased slightly more than DOPAC dialysate levels. 4. Stimulatory
      action of trans-carbidine on locomotor activity of non-operated rats has been
      observed at doses 0.2 and 0.5 mg/kg, i.p.. 5. Only the dose 25 mg/kg of trans
      carbidine (maximal calculated IFC 4.53 mu M) was found to be cataleptogenic. The
      drug at this dose failed to increase DA release but induced a marked increase of
      DOPAC and HVA output. 6. It is concluded that trans-carbidine in in vivo
      neurochemical and behavioural studies demonstrates the preferential antagonistic
      action on dopamine release-regulating autoreceptors.

PMID- 8861195
TI  - Serotonergic serotonin 2 receptor modulation on DOPAC and 5-HIAA levels in rat
      striatum and nucleus accumbens: microdialysis studies of freely moving rats.
AB  - 1. In vivo microdialysis with microbore-HPLC/ECD was employed to examine and
      compare changes of monoaminergic metabolites, dihydroxyphenylacetic acid (DOPAC)
      and 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens (NuAc) and the
      neostriatum (Str) of freely moving rats, following systemic administration of the
      specific 5-HT(2) analogue. 2. The 5-HT(2) agonist decreased DOPAC and 5-HIAA in
      both the NuAc and Str. However, the effect produced by apomorphine only decreased
      the DOPAC level in these two areas. 3. This effect did not occur in the rats that
      had been pretreated with the serotonin (5-HT) depleting agent. However, the
      effect was found in the rats that the striatal neurons had been damaged. 4. The 5
      HT(2) effect regulated the mesencephalic dopamine (DA) synthesis/turnover only
      when entirely influenced by 5-HT. The striato-nigral feedback loop was not
      involved in this effect. Additionally, presynaptic relationship probably occurred
      between the 5-HT and its innervated DA pathways.

PMID- 8861196
TI  - Effect of L-alpha glycerylphosphorylcholine on muscarinic receptors and membrane
      microviscosity of aged rat brain.
AB  - 1. Old rats showed a significant decrease in the number of muscarinic M(1)
      receptors and a significant increase in membrane microviscosity in the striatum
      and hippocampus as compared to young animals. In contrast, no significant changes
      in the density of muscarinic M(2) receptors were observed with aging. 2. Chronic
      treatment of aged rats with L-alpha-glycerylphosphorylcholine (L-alpha-GPC)
      restored the number of M(1) receptors to levels found in the striatum and
      hippocampus from young animals. The same treatment to aged rats partially
      restored membrane microviscosity in both regions studied and hence increased
      membrane fluidity. 3. None of the major metabolites of L-alpha-GPC (choline,
      glycerophosphate or phosphorylcholine) was able to restore the number of striatal
      and hippocampal M(1) sites and membrane microviscosity of aged rats, neither did
      any of these treatments (including treatment with L-alpha-GPC) modify the level
      of M(1) receptors and microviscosity values in young rats.

PMID- 8861197
TI  - An acute psychotic disorder caused by pefloxacin: a case report.
AB  - 1. The patient, a 59 year old woman, developed a state of acute excitation
      several hours after the administration of 400 mg of the fluorquinolone pefloxacin
      in combination with 1000 mg paracetamol. Nine days later, after a total dosage of
      pefloxacin of 800 mg, she was admitted to our hospital with a psychotic disorder.
      2. There was a full remission of symptoms after treatment with perazine up to a
      dosage of 500 mg/day. 3. Three years ago, the patient had developed a manic state
      under a medication with corticosteroids. 4. So far, the mechanism of--in this
      case--long-lasting central nervous side effects of fluorquinolones is not known.
      In patients with increased vulnerability of the CNS or in advanced age the
      application of fluorquinolones should be considered critically, in particular in
      combination with non-steroidal anti-inflammatory drugs.

PMID- 8861198
TI  - Structure, function and controls in microbial division.
AB  - Several crucial genes required for bacterial division lie close together in a
      region called the dcw cluster. Within the cluster, gene expression is subject to
      complex transcriptional regulation, which serves to adjust the cell cycle in
      response to growth rate. The pivotally important FtsZ protein, which is needed to
      initiate division, is now known to interact with many other components of the
      division machinery in Escherichia coli. Some biochemical properties of FtsZ, and
      of another division protein called FtsA, suggest that they are similar to the
      eukaryotic proteins tubulin and actin respectively. Cell division needs to be
      closely co-ordinated with chromosome partitioning. The mechanism of partitioning
      is poorly understood, though several genes involved in this process, including
      several muk genes, have been identified. The min genes may participate in both
      septum positioning and chromosome partitioning. Coupled transcription and
      translation of membrane-associated proteins might also be important for
      partitioning. In the event of a failure in the normal partitioning process,
      Bacillus subtilis, at least, has a mechanism for removing a bisected nucleoid
      from the division septum.

PMID- 8861199
TI  - Bacterial signalling involving eukaryotic-type protein kinases.
AB  - Protein Ser, Thr and Tyr kinases play essential roles in signal transduction in
      organisms ranging from yeast to mammals, where they regulate a variety of
      cellular activities. During the last few years, a number of genes that encode
      eukaryotic-type protein kinases have also been identified in four different
      bacterial species, suggesting that such enzymes are also widespread in
      prokaryotes. Although many of them have yet to be fully characterized, several
      studies indicate that eukaryotic-type protein kinases play important roles in
      regulating cellular activities of these bacteria, such as cell differentiation,
      pathogenicity and secondary metabolism. A model based on the possible coupling
      between two-component systems and eukaryotic-type protein kinases is proposed to
      explain the function of eukaryotic-type protein kinases in bacterial signalling
      in the light of studies in bacteria, as well as in plants and yeast. These two
      groups of eukaryotes possess signal-transduction pathways involving both two
      component systems and eukaryotic protein kinases.

PMID- 8861200
TI  - Atomic structure and specificity of bacterial periplasmic receptors for active
      transport and chemotaxis: variation of common themes.
AB  - Crystallographic structure refinement at very high resolutions of a dozen
      periplasmic receptors has revealed that, though they have different sizes (26 to
      60 kDa) and little sequence homology, they have high tertiary structure
      similarity. They consist of two distinct globular domains bisected by a cleft or
      groove wherein the ligand binds and is buried by a hinge-bending motion between
      the two domains. Structural analysis also reveals how hydrogen-bonding
      interactions can be tailored to a wide spectrum of specificity, ranging from the
      stringent specificity for phosphate and sulphate to the more loose specificity
      for peptides.

PMID- 8861201
TI  - Molecular biology of iron acquisition in Saccharomyces cerevisiae.
AB  - In recent years, significant advances have been made in our understanding of the
      mechanism and regulation of elemental iron transport in the eukaryote
      Saccharomyces cerevisiae. This organism employs two distinct iron-transport
      systems, depending on the bioavailability of the metal. In iron-replete
      environments, a low-affinity transport system (K(m) = 30 microM) is used to
      acquire iron. This system may also be used to acquire other metals including
      cobalt and cadmium. When environmental iron is limiting, a high-affinity (K(m) =
      0.15 microM) iron-transport system is induced. Genetic studies in S. cerevisiae
      have identified multiple genes involved in both iron-transport systems. Cell
      surface reductases, FRE1 and FRE2, provide ferrous iron for both systems. A non
      ATP-dependent transmembrane transporter (FET4) has been identified as the main
      component of low-affinity transport. One gene identified to date as part of the
      high-affinity transport system is FET3, which shows high sequence and functional
      homology to multicopper oxidases. Accessory genes required for the functioning of
      this transport system include a plasma-membrane copper transporter (CTR1), an
      intracellular copper transporter (CCC2), and a putative transcription factor
      (AFT1). The mechanism by which these genes act in concert to ensure iron
      accumulation in S. cerevisiae presents an intriguing picture, drawing parallels
      with observations made in the human system almost 40 years ago.

PMID- 8861202
TI  - The sxa2-dependent inactivation of the P-factor mating pheromone in the fission
      yeast Schizosaccharomyces pombe.
AB  - Haploid cells of the fission yeast Schizosaccharomyces pombe exist in one of two
      mating types, referred to as M and P. Conjugation occurs between cells of
      opposite mating type and is controlled by the reciprocal action of diffusible
      pheromones. Loss of function of the sxa2 gene in M cells causes hypersensitivity
      to the P-factor mating pheromone and a reduction in mating efficiency. Here we
      demonstrate the secretion of an sxa2-dependent carboxypeptidase that inactivates
      P-factor by removal of the C-terminal leucine residue.

PMID- 8861203
TI  - Integration of SecA protein into the Escherichia coli inner membrane is regulated
      by its amino-terminal ATP-binding domain.
AB  - SecA protein, the ATPase promoting translocation of proteins across the
      Escherichia coil inner membrane, contains two ATP-binding domains that differ
      greatly in their affinity for bound nucleotide. In order to define more precisely
      the location of the high-affinity nucleotide-binding site, oligonucleotide
      directed mutagenesis was used to introduce cysteine residues into the SecA
      sequence, and a cysteine-specific cleavage reagent was employed to generate
      defined peptides of SecA protein after photocross-linking with [alpha-(32)P]-ATP.
      This analysis revealed that the nucleotide was cross-linked between amino acid
      residues 75 and 97 of SecA protein. The biochemical function of the high affinity
      ATP-binding domain was explored by subcellular fractionation studies which
      demonstrated that SecA proteins defective in this region were found almost
      exclusively in their integral membrane form, while SecA proteins with defects in
      the low-affinity ATP-domain showed a normal distribution of cytosolic, peripheral
      and integral membrane forms. Interestingly, the SecA51(Ts) protein that has a Leu
      to Pro substitution at amino acid residue 43 bound ATP with high affinity, but
      its fractionation pattern and translocation ATPase activity were similar to those
      of proteins with defects in the high-affinity ATP-binding site. These results
      delimit more precisely the high-affinity ATP-binding domain of SecA, indicate the
      importance of the early amino-terminal region of SecA protein in the functioning
      of this domain, and demonstrate the role of this domain in regulating penetration
      of SecA protein into the inner membrane. Our results lead to a simple model for
      the regulation of a cycle of SecA insertion into, and de-insertion from, the
      inner membrane by the activity of the high affinity ATP-binding domain.

PMID- 8861204
TI  - Functional analysis of the Enterococcus faecalis plasmid pAD1-encoded stability
      determinant par.
AB  - The molecular organization and functional characteristics of the PAD1 replicon
      encoded par stability determinant were examined. par encodes two convergently
      transcribed RNAS of approximately 210 and 65 nucleotides designated RNA I and RNA
      II, respectively. The sequence of RNA II is largely complementary to RNA I,
      suggesting that RNA II could regulate RNA I function as an anti-sense RNA.
      Results of functional studies are consistent with a role for par as a post
      segregational killing system, the first to be identified in Gram-positive
      bacteria, with RNA I encoding the toxin and RNA II the antidote. These results
      include: (i) destabilization of par-containing replicons in the presence of a
      second complete par or the RNA II coding sequence in the same cell; (ii) par
      dependent stabilization of a highly unstable vector at the expense of host-cell
      growth rate; and (iii) protection of cells from the toxic effects of
      overexpression of RNA I by RNA II supplied in trans.

PMID- 8861205
TI  - Cloning of a second gene encoding 5-phosphofructo-2-kinase in yeast, and
      characterization of mutant strains without fructose-2,6-bisphosphate.
AB  - We have identified a new gene, PFK27, that encodes a second inducible 6
      phosphofructo-2-kinase in the yeast Saccharomyces cerevisiae. Sequencing shows an
      open reading frame of 397 amino acids and 45.3 kDa. Amino acid sequence
      comparisons with other bifunctional 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase isoenzymes of various organisms revealed similarities only to the
      kinase domains. Expression of PFK27 was induced severalfold by glucose and
      sucrose, but not by galactose or maltose, suggesting that sugar transport might
      be involved in triggering the induction signal. We have constructed a mutant
      strain devoid of any fructose-2,6-bisphosphate. The mutant strain grew well on
      several kinds and concentrations of carbon sources. The levels of hexose
      phosphates in the cells were increased, but flux rates for glucose utilization
      and ethanol production were similar to the wild-type strain. However, after the
      transfer of the mutant cells from respiratory to fermentative growth conditions,
      growth, glucose consumption and ethanol production were delayed in a transition
      phase. Our results show that fructose-2,6-bisphosphate is an important effector
      in vivo of the 6-phosphofructo-1-kinase/fructose-1 ,6-bisphosphatase enzyme pair,
      and is involved in the initiation of glycolysis during the transition to a
      fermentative mode of metabolism. Nevertheless, it can be effectively replaced by
      other effectors and regulatory mechanisms during growth on glucose.

PMID- 8861206
TI  - Purification and characterization of a histone-like protein from the Archaeal
      isolate AN1, a member of the Thermococcales.
AB  - We have purified and characterized the histone-like protein, termed HAN1, and an
      HAN1-associated DNA-binding protein (hDBP) from nucleoids of the
      hyperthermophilic Thermococcus-like AN1. HAN1 is shown to be composed of two
      subunits, to be thermally stable and to compact DNA in a reversible manner. The N
      terminal sequence of HAN1 shares a high degree of homology with HMf, the histone
      like protein from Methanothermus fervidus. Consistent with this, the toroidal
      wrapping of DNA by HAN1 resembles that described for HMf. However, significant
      differences in both twist and writhe components of these complexes are indicated
      by the 12.0 bp helical repeat produced during hydroxyl radical footprinting with
      HAN1. Furthermore, the increased stability of HAN1: DNA complexes allows DNA to
      be protected from thermal denaturation and cleavage by the restriction enzyme
      TaqI at 65 degrees C. The hDBP, which co-purified with HAN1,is shown to represent
      a major portion of the acid-washed nucleoid protein in AN1 and to enhance the
      mobility of DNA directly, yet decrease the mobility of HAN1:DNA complexes.

PMID- 8861207
TI  - The bundle-forming pili of enteropathogenic Escherichia coli: transcriptional
      regulation by environmental signals.
AB  - The bundle-forming pili (BFP) of enteropathogenic Escherichia coil (EPEC) are
      required for the development of circumscribed colonies of bacteria attached to
      the surfaces of cultured epithelial cells, a process termed the localized
      adherence (LA) phenotype. Similar lesions are evident in jejunal biopsies from
      EPEC-infected children. BFP production is not constitutive, but instead occurs
      upon transfer of bacteria from nutrient broth to tissue culture media, indicating
      that the expression of BFP may be environmentally regulated. To learn more about
      how BFP protein expression is induced during epithelial-cell adherence, bfpA-cat
      transcriptional fusions and northern blot analyses were employed to monitor bfpA
      expression as a function of environmental signals and growth kinetics. bfpA
      expression was found to be regulated at the transcriptional level, and to require
      a separate locus on the EPEC adherence factor (EAF) plasmid. Expression occurred
      selectively during exponential-growth phase and was greatest between 35 and 37
      degrees C, and in the presence of calcium. Ammonium (20 mM) significantly reduced
      bfpA mRNA and protein expression and the development of the LA phenotype.
      Analysis of the bfpA upstream sequence and identification of the transcription
      initiation site revealed a conventional sigma (70)-dependent promoter and an AT
      rich tract that might affect promoter activity. Taken together, these findings
      further support the pathogenic role of BFP by explaining how BFP production would
      commence in the small intestine and terminate in the colon and in external
      habitats.

PMID- 8861208
TI  - Dimerization of plasmid DNA accelerates selection for antibiotic resistance.
AB  - Dimerization of multicopy plasmids is widely assumed to be disadvantageous both
      for plasmid maintenance and for the host cell. It is known that dimerization
      causes plasmid instability; dimer-containing cells grow slower than their monomer
      containing counterparts. However, as we demonstrate here, under conditions of
      selective stress, dimers provide an advantage for bacteria. Dimers facilitate
      segregation of mutants from numerous copies of the parental plasmid. Accelerated
      segregation greatly increases the rate of accumulation of plasmids carrying
      mutations that are adaptive for bacteria. In contrast, resolution of dimers by
      site-specific recombination decreases, 10(3)-10(5)-fold, the efficiency of
      selection of spontaneous reversions in the tet gene of pBR327.

PMID- 8861209
TI  - The ATP-binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae:
      a novel target for the transcription factors Pdr1 and Pdr3.
AB  - Pleiotropic drug resistance (PDR) in the yeast Saccharomyces cerevisiae can arise
      from overexpression of ATP-binding cassette (ABC) efflux pumps such as Pdr5 and
      Snq2. Mutations in the transcription factor genes PDR1 and PDR3 are also
      associated with PDR. We show here that a pdr1-3 mutant exhibits a PDR phenotype,
      including elevated resistance to the mutagen 4-nitroquinoline-N-oxide, a known
      substrate for Snq2 but not for Pdr5. Northern analysis and immunoblotting
      demonstrated that the SNQ2 gene is 10-fold overexpressed in a pdr1-3 gain-of
      function mutant strain, whereas Snq2 expression is severely reduced in a delta
      pdr1 deletion strain, and almost abolished in a delta pdr1 delta pdr3 double
      disruptant when compared to the PDR1 strain. However, expression of the Ste6 a
      factor pheromone transporter, another yeast ABC transporter not associated with
      PDR, is unaffected in pdr1-3 mutant cells and in strains carrying delta pdr1,
      delta pdr3, or delta pdr1 delta pdr3 deletions. Finally, DNA footprint analysis
      revealed that the SNQ2 promoter contains three binding sites for Pdr3. Our
      results identify SNQ2 as a novel target for both Pdr1 and Pdr3, and demonstrate
      that the PDR phenotype of a pdr1-3 mutant strain results from overexpression of
      more than one ABC drug-efflux pump.

PMID- 8861210
TI  - Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major
      virulence determinant of Listeria monocytogenes.
AB  - Infection of a murine-spleen dendritic cell line by Listeria monocytogenes was
      found to induce cell death through apoptosis. To characterize the bacterial
      product(s) involved in induction of apoptosis, dendritic cells were infected with
      the L. monocytogenes EGD strain and several isogenic mutants deficient in the
      production of individual listerial virulence factors. The ability to induce
      cellular apoptosis was retained by all mutants tested, except the prfA and delta
      hly mutants, both of which are unable to produce listeriolysin. Apoptosis was
      also induced by purified listeriolysin suggesting that this protein directly
      induces apoptosis. Purified recombinant listeriolysins rendered either weakly
      haemolytic by a C-484 to S mutation, or nonhaemolytic by a W-491 to A mutation
      exhibited little or no capacity to induce apoptosis, indicating that both
      activities are associated within the same protein region. Treatment with purified
      listeriolysin or L. monocytogenes infection also triggers apoptosis in explanted
      bone-marrow dendritic cells. Thus invasion of dendritic cells by L.
      monocytogenes, which results in cell death, may play an important role in the
      pathogenesis of listerial infections by impairing immune responses, hindering
      bacterial clearance and promoting spread of the infection.

PMID- 8861211
TI  - Involvement of N-acyl-L-hormoserine lactone autoinducers in controlling the
      multicellular behaviour of Serratia liquefaciens.
AB  - Several bacterial species possess the ability to differentiate into highly motile
      swarmer cells capable of rapid surface colonization. In Serratia liquefaciens, we
      demonstrate that initiation of swarmer-cell differentiation involves diffusible
      signal molecules that are released into the growth medium. Using high-performance
      liquid chromatography (HPLC), high resolution mass spectrometry and nuclear
      magnetic resonance (NMR) spectroscopy, we identified N-butanoyl-L-homoserine
      lactone (BHL) and N-hex anoyl-L-homoserine lactone (HHL) in cell-free Serratia
      culture supernatants. BHL and HHL are present in a ratio of approximately 10:1
      and their structures were unequivocally confirmed by chemical synthesis. The swrl
      (swarmer initiation) gene, the predicted translation product of which exhibits
      substantial homology to the LuxI family of putative N-acyl homoserine lactone
      (AHL) synthases is responsible for directing synthesis of both BHL and HHL. In an
      swrl mutant, swarming motility is abolished but can be restored by the addition
      of an exogenous AHL. These results add swarming motility to the rapidly expanding
      list of phenotypes known to be controlled through quorum sensing.

PMID- 8861212
TI  - Vibrio parahaemolyticus FlaJ, a homologue of FliS, is required for production of
      a flagellin.
AB  - The flaA locus of Vibrio parahaemolyticus encodes one of the four polar flagellin
      genes, the flagellum-capping protein HAP2, and three additional flagellar genes.
      Sequence analysis downstream of the gene encoding HAP2 revealed the region to be
      similar to the fliD (HAP2) locus of Pseudomonas aeruginosa. The deduced protein
      sequences for the newly identified genes suggest that one protein belongs to the
      family of transcriptional regulatory proteins known to interact with sigma (54),
      one may be a rod component of the flagellum, and one resembles the FliS protein.
      fliS is an essential flagellar gene in many bacteria; however its function is not
      clear. The V. parahaemolyticus polar flaC flagellin gene was poorly expressed in
      Escherichia coli Production of FlaC was stimulated by provision of the flaA locus
      in trans. Dissection of this locus revealed that the fliS-like gene, flaJ, was
      required for increased expression of flaC. Stimulation by FlaJ occurred in E.coli
      mutants defective in either the master flagellar-controlling operon or the gene
      encoding the flagellar sigma (28). Therefore the effect of FlaJ was not mediated
      through flagellar proteins. Nor was it mediated through sigma (54) for enhanced
      FlaC production was observed in mutants with defects in the gene encoding sigma
      (54).

PMID- 8861214
TI  - Tandem repeats of the tetramer 5'-CAAT-3' present in lic2A are required for phase
      variation but not lipopolysaccharide biosynthesis in Haemophilus influenzae.
AB  - A novel lipopolysaccharide (LPS) biosynthesis gene, lic2B, which is required for
      the biosynthesis of a phase-variable LPS structure expressed by Haemophilus
      influenzae RM7004 is described. The product of this gene is homologous to Lic2A
      and the recently described LPS biosynthetic enzymes, LgtB from Neisseria
      gonorrhoea and LgtE from Neisseria meningitidis, and LpsA from Pasteurella
      haemolytica. Of this family of enzymes only Lic2A contains the repetitive
      tetrapeptide motif (SINQ)(n) encoded by multiple tandem repeats of 5'-CAAT-3'.
      This observation suggested that (SINQ)(n) might not be a prerequisite for the
      catalytic activity of this protein. To address this hypothesis, we deleted the 5'
      CAAT-3' repeats from lic2A so that the protein encoded by the modified gene was
      analogous to Lic2B. This mutation had no apparent effect on the overall apparent
      molecular weight of LPS as judged by Tricine-SDS-PAGE and did not affect ability
      to react with monoclonal antibody 4C4. It was therefore concluded that (SINQ)(n)
      is not a prerequisite for the enzymatic function of Lic2A and that the 5'-CAAT-3'
      repeats in lic2A function solely as a mechanism for generating phase variation.
      This observation suggested that wide variation in the number of 5'-CAAT-3'
      repeats might be tolerated in lic2A, and this was confirmed by surveying the
      number of 5'-CAAT-3' repeats in a range of different H. influenzae strains. The
      predicted secondary structure of (SINQ)(n) indicates that it forms a highly
      flexible random coiled structure, which is unlikely to impede formation of the
      domains that may be required for catalytic activity. This characteristic is also
      a feature of repetitive tetrapeptides encoded by other tetrameric repeats located
      within coding sequences present on the chromosome of H. influenzae Rd.

PMID- 8861213
TI  - Identification of a Salmonella virulence gene required for formation of
      filamentous structures containing lysosomal membrane glycoproteins within
      epithelial cells.
AB  - Salmonella species are facultative intracellular pathogens that invade epithelial
      cells and reside within lysosomal membrane glycoprotein (lgp)-containing
      vacuoles. Coincident with the onset of bacterial replication inside these
      vacuoles, Salmonella induce the formation of stable lgp-containing filamentous
      structures that connect with the Salmonella-containing vacuoles. Salmonella
      typhimurium SL1344::Tn l0dCm mutant strains unable to induce these structures
      were isolated. All contained insertions within a novel Salmonella induced
      filament gene A (sifA). sifA is present only in Salmonella species and encodes a
      protein with a predicted molecular mass of 38 kDa and an apparent molecular mass
      of 35 kDa. sifA is flanked by 300 base pairs, and sifA and its flanking DNA show
      no homology to sequences in DNA databases. sifA is located within the potABCD
      operon, a housekeeping locus involved in periplasmic transport of polyamines.
      Fourteen-base-pair direct repeats mark the probable site of integration of sifA
      and its flanking DNA have a significantly reduced G+C content (41%) when compared
      with the potABCD operon (51%) and the Salmonella genome (52-54%). Deletion mutant
      strains in sifA or in the downstream potC were constructed. Delta sifA does not
      produce Salmonella-induced filaments in epithelial cells, and is attenuated in
      mice. Delta potC produces Salmonella-induced filaments in epithelial cells, and
      was fully virulent. Collectively, these results suggest that sifA arose by
      horizontal gene transfer into Salmonella and its product is involved in a
      virulence-associated intracellular phenotype related to Salmonella-induced
      filament formation.

PMID- 8861215
TI  - Complementation of deletion mutations in a cloned functional cluster of Erwinia
      chrysanthemi out genes with Erwinia carotovora out homologues reveals OutC and
      OutD as candidate gatekeepers of species-specific secretion of proteins via the
      type II pathway.
AB  - The type II or Sec-dependent secretion system is used by diverse Gram-negative
      bacteria for secretion of extracellular proteins. Of the 12-15 proteins involved
      in secretion, the requirement for many has not been demonstrated and little is
      known about their functions in the secretion process. The plant pathogens Erwinia
      chrysanthemi and Erwinia carotovora secrete extra-cellular pectate lyases (Pels)
      using the type II or Out pathway. However, these two bacteria cannot secrete Pels
      encoded by heterologously expressed genes from the other species, suggesting the
      presence of species-specific recognition factors in the Out systems of the two
      Erwinia species. We previously reported the isolation of a cosmid clone,
      pCPP2OO6, from E. chrysanthemi EC16, which enables Escherichia coil to secrete
      heterologously expressed E. chrysanthemi Pels. Sequencing in a region required
      for secretion revealed the presence of 12 genes, outC-M and outO. We report here
      the construction of functionally non-polar mutations in each gene in the outC-M
      operon and outS and outB using a polA(ts) strain of E. coli to facilitate
      homologous recombination between out genes carrying deletions and their wild-type
      copies on pCPP2006. By testing for complementation of each deletion with wild
      type out genes from E. chrysanthemi EC16 and E. carotovora SCRI193 we have
      demonstrated that: (i) each out gene is required for secretion of E. chrysanthemi
      PelE from E. coli with the exception of outH; (ii) each mutation can be
      complemented by its homologue from E. carotovora, except for outC and outD; (iii)
      outC and outD from E. carotovora do not confer secretion of Pel1 on the E.
      chrysanthemi Out system; and (iv) Pel1 secretion can be conferred on the E.
      chrysanthemi Out system by the presence of outC-M, S and B from E. carotovora.
      The data suggest that OutC and OutD are gatekeepers of the Out system involved in
      recognition of Pels targeted for secretion but that OutC and OutD from E.
      carotovora cannot be successfully assembled into the E. chrysanthemi Out system.

PMID- 8861216
TI  - Induction of haemolytic activity in Escherichia coli by the slyA gene product.
AB  - The Salmonella typhimurium protein SlyA(ST), originally described as a cytolysin,
      shows sequence similarities to several known bacterial regulatory proteins. A
      homologue to the Slya(ST) gene has been localised to min 37 of the Escherichia
      coil K-12 chromosome and has been designated SlyA(EC). When introduced in trans
      on a plasmid, the SlyA(EC) gene conferred a haemolytic phenotype on wild-type but
      not clyA-knockout strains of E. coli K-12. The clyA gene encodes a novel
      haemolysin that is not expressed by wild-type E. coli under tested laboratory
      conditions. Western and Northern blot analyses, and DNA-band-shift assays support
      a model whereby the SlyA(EC) protein activates clyA expression by binding to the
      clyA promoter region, thereby supporting the sequence similarity data in
      suggesting that SlyA(ST) is a haemolysin activator rather than being a haemolysin
      per se.

PMID- 8861218
TI  - Genetic footprint on the ToxR-binding site in the promoter for cholera toxin.
AB  - The transmembrane DNA-binding protein, ToxR, of Vibrio cholerae is a global
      transcriptional regulator of virulence gene expression. ToxR has been shown to
      interact with promoter regions upstream of both the ctxAB operon encoding cholera
      toxin, and the regulatory gene toxT. Deletion analysis has shown that a repeated
      sequence, TTTTGAT, is required for ToxR binding and activation of the ctxAB
      promoter. However, this sequence is not found upstream of the toxT promoter.
      Genetic selections using P22 challenge phages were used to define sites within
      the promoter for ctxAB which are critical for ToxR-DNA interactions. Single-base
      pair changes and deletion mutations that impair ToxR binding cluster within two
      regions: -57 to -69 within two of three tandem TTTTGAT sequences; and from -39 to
      -47, between the repeat sequences; and the -35 region of the promoter. ToxR does
      not bind to a synthetic target that has three tandem repeats which lack a
      flanking upstream and downstream sequence. These results suggest that the ToxR
      binding site lies immediately upstream of the - 35 position of the ctx promoter,
      and that the affinity of ToxR binding to this site is influenced by the repeat
      sequences.

PMID- 8861219
TI  - Conserved amino acids in the N- and C-terminal domains of integral membrane
      transporter FhuB define sites important for intra- and intermolecular
      interactions.
AB  - Transport of iron(III) hydroxamates across the inner membrane of Escherichia coli
      is mediated by a peri-plasmic binding protein-dependent transport (PBT)
      mechanism. FhuB, the integral membrane component of the system, is composed of
      covalently linked halves (FhuB[N] and FhuB[C]) which still function when present
      as two distinct polypeptide chains. Our analysis of two uptake-deficient FhuB
      derivatives provides evidence for a mechanistically novel type of functional
      complementation: 'domain displacement' in the cyto-plasmic membrane. Amino acid
      residues 60 and 426 in the FhuB polypeptide chain may define key positions that
      are important for FhuB[N]-FhuB[C] interaction. Furthermore, FhuB derivatives,
      altered in either one of their conserved regions--typical of PBT related integral
      membrane proteins--displayed a dominant negative effect on ferric hydroxamate
      transport. The experimental data suggest that the two functionally equivalent
      conserved regions in FhuB[N] and FhuB[C] are primarily involved in the
      interaction with another component of the transport system, probably FhuC.

PMID- 8861217
TI  - Altering the level and regulation of the major sigma subunit of RNA polymerase
      affects gene expression and development in Bacillus subtilis.
AB  - In Bacillus subtilis, the major sigma factor, sigma-A (rpoD), and the minor sigma
      factor, sigma-H (spo0H), are present during growth and are required for the
      initiation of sporulation. Our experiments indicate that sigma-A and sigma-H
      compete for binding to core RNA polymerase. We used a fusion of rpoD to the LacI
      repressible IPTG-inducible promoter, Pspac, to vary the levels of sigma-A in the
      cell. Increasing the amount of sigma-A caused a decrease in expression of genes
      controlled by sigma-H, and a delay in the production of heat-resistant spores.
      Decreasing the amount of sigma-A, in a strain deleted for the chromosomal rpoD,
      caused an increase in expression of genes controlled by sigma-H. As rpoD itself
      is controlled by at least two promoters recognized by RNA polymerase that
      contains sigma-H, the effect of sigma-A levels on expression of sigma-H
      controlled promoters represents a feedback mechanism that might contribute to
      maintaining appropriate levels of sigma-A. While the level of sigma-A was
      important for efficient sporulation, our results indicate that the normal
      transcriptional control of rpoD, in the context of the rpoD operon and the
      numerous promoters in that operon, is not required for efficient sporulation or
      germination, provided that the sigma-A level from a heterologous promoter is
      comparable to that in wild-type cells.

PMID- 8861220
TI  - Electrospray ionization mass spectrometric analysis of phospholipids of
      Escherichia coli.

PMID- 8861221
TI  - Comment on the MicroReview by B. Craig Lee (Quelling the red menace: haem capture
      by bacteria)

PMID- 8861236
TI  - The effects of glucose on nonmemory cognitive functioning in the elderly.
AB  - The present study evaluated the role of glucose in the performance of a series of
      memory and nonmemory neuropsychological tasks. Each of the 28 healthy (no
      evidence of diabetic or dementing disease), elderly (mean age = 73), subjects
      participating in the study were tested under each of two conditions (50 g glucose
      or 27.3 mg saccharin) in a counterbalanced fashion. While actively manipulating
      glucose levels in participants, blood glucose (BG) levels were monitored to
      evaluate the effectiveness of individual subject's regulation of ingested
      glucose. It was hypothesized that glucose would enhance performance on a memory
      measure (Rey/Taylor Figure) as well as other nonmemory measures (e.g. design
      fluency, trail making test, etc.). A repeated measures, counterbalanced design
      was used to evaluate the direct manipulation of glycemic condition. Results
      reveal an enhancement effect on both the recall of the Rey/Taylor Figure as well
      as verbal fluency and figural fluency. A significant correlation between glycemic
      regulation and performance on a test of divided attention (dichotic listening)
      was also evident (r = -0.47). These findings suggest that a specific facilitation
      of retrieval mechanisms may account for enhancement of both memory and fluency
      performance.

PMID- 8861237
TI  - Is left always right? Directional deviations in visual line bisection as a
      function of hand and initial scanning direction.
AB  - Directional deviations in visual line bisection were investigated using normal
      subjects. Significant main effects were found for hand and initial scan direction
      resulting from significantly greater deviations to the left by the left hand
      compared with the right hand and by a scan from the left compared with a scan
      from the right. These results suggest that the amelioration of neglect can only
      be inferred from the left hand deviations of neglect patients if they are
      significantly leftwards of the objective middle and that the degree of leftward
      deviation in normal subjects results from an interaction between right
      hemispheric activation and unilateral allocation of attention.

PMID- 8861238
TI  - Detecting directional hypokinesia: the epidiascope technique.
AB  - A new technique to detect directional hypokinesia is proposed.. Subjects with
      unilateral neglect were administered cancellation tests with an epidiascope used
      to dissociate visual input from motor output. Two different cancellation tasks
      were performed in order to compare this technique with the method devised by
      Tegner and Levander [Brain 114, 1943-1951, 1991]. No difference in detecting
      hypokinetic deficits was observed; however, our method was easier to perform and
      more suitable for clinical testing.

PMID- 8861241
TI  - A method of screening for mutant proteins containing cysteine residues using
      fluorescein-5-maleimide.
AB  - A method of screening transformed bacterial colonies for introduction of a
      cysteine residue into an overexpressed protein is described. After treating SDS
      extracts of induced bacterial cells with fluorescein-5-maleimide, the proteins
      containing cysteine were visible on SDS-PAGE gels under ultraviolet light as
      fluorescent bands. If the wild-type protein contains no endogenous cysteine
      residues, then mutant proteins containing cysteine may be easily identified by
      their fluorescence. In addition, a shift in electrophoretic mobility of modified
      proteins was observed, with mutant proteins containing cysteine at more than one
      site exhibiting incremental decreases in electrophoretic mobility. This effect
      permits the detection of cysteine mutations even when endogenous cysteines are
      present. The described method allows the rapid screening of a large number of
      transformants.

PMID- 8861273
TI  - Mobilization and selection of CD34-positive hematopoietic progenitors.
AB  - High-dose chemotherapy with autologous hematopoietic progenitor-cell support is
      increasingly used for the treatment of hematologic malignancies and solid tumors.
      Over the last few years, the major source of progenitor cells for clinical use
      has shifted from bone marrow to peripheral blood. The current approaches on
      peripheral blood progenitor-cell mobilization and collection is examined. The
      isolation of CD34-positive cells from peripheral blood progenitor-cell grafts for
      tumor purging is the autologous transplant setting and for T-cell depletion in
      the allogeneic transplant setting is also discussed.

PMID- 8861274
TI  - Thrombocytopenia in pregnancy: diagnosis, pathogenesis and management.
AB  - Maternal thrombocytopenia is a common find during pregnancy. The rapid
      determination of its cause can often be difficult, with the diagnosis only being
      made in retrospect once the course of the platelet count is known. The majority
      of patients with thrombocytopenia in pregnancy will have incidental
      thrombocytopenia of pregnancy which is of no clinical significance.

PMID- 8861275
TI  - The importance of cytoskeleton proteins in megakaryocyte spreading and platelet
      formation.
AB  - The release of platelets into the circulation is preceded by considerable
      morphologic change of the parent megakaryocyte. The cell extends cytoplasmic
      processes into the venous sinusoids, which develop constrictions at intervals,
      revealing putative platelets. The pattern of cytoskeletal distribution changes
      during the spread of megakaryocytes in vitro. In this review, an attempt was made
      to summarize the data of the literature concerning the changes in the
      cytoskeletal pattern of megakaryocytes during their spreading and platelet
      formation.

PMID- 8861276
TI  - Pure red-cell aplasia: a review.
AB  - Pure red-cell aplasia is an anemia characterized by a near absence of nucleated
      red blood cells. It can be congenital or acquired. The congenital form is
      probably induced by intrauterine damage to early erythroid stem cells. The
      acquired form can be transient and self-limited or sustained and lifelong. Many,
      if not most, cases of transient pure red-cell aplasia are caused by the B19
      parvovirus, which has a special affinity for erythroid progenitor cells. When
      complicating an underlying hemolytic anemia, the anemia may be acute and severe.
      Sustained aplasia is caused by viral invasion, immune rejection or toxic
      destruction of progenitor or precursor cells. It occurs most often in patients
      with a benign or malignant lymphoid disease. Treatment with immunosuppressive
      drugs--especially corticosteroids--will in most cases cause a temporary or
      permanent remission. The final outcome depends primarily on the underlying
      disorder.

PMID- 8861277
TI  - The pathophysiology of vascular obstruction in the sickle syndromes.
AB  - Vasocclusive events in the sickle-cell syndromes have multiple determinants:
      first and foremost is the capacity of red cells to undergo intracellular
      polymerization of deoxy HbS. However, the impact of the sicklable red cell is not
      limited to mechanical obstruction of the microcirculation, but also results in
      other and sometimes unexpected consequences. For example, red-cell destruction
      leads to large numbers of young red cells with enhanced vascular adhesion and
      increased K:Cl cotransport expression, in addition to an elevated percent of
      erythrocytic HbF. These pleiotropic effects, that is, multiple phenotypic effects
      from a single gene, can be further modulated by the action of epistatic effects,
      that is, the action of other genes besides beta(S). The interaction of epistatic
      and pleiotropic effects leads to the interindividual phenotypic variations
      characteristic of sickle-cell disease. Further understanding of pleiotropic
      effects (i.e. mechanism of red-cell adhesion, production of vasoactive substances
      by damaged endothelium, etc.), will uncover new epistatic effects. At the end, we
      will be able to define not only the genotype, but also the phenotypic severity.
      This review covers the present knowledge of the red-cell and non-red-cell
      determinants of vasocclusion, and proposes models to explain the acute painful
      crises that commonly afflict these patients.

PMID- 8861278
TI  - G6PD: population genetics and clinical manifestations.
AB  - The glucose-6-phosphate dehydrogenase (G6PD) gene is X-linked. There are numerous
      mutations that cause a deficiency of this enzyme in erythrocytes. G6PD deficiency
      can produce anemia, both when drugs are administered and under the stress induced
      by infection. Functionally severe variants cause hereditary non-spherocytic
      hemolytic anemia, i.e. anemia even in the absence of stress. Neonatal jaundice
      occurs in G6PD deficiency, but it is likely that it is largely due to impairment
      of liver function, rather than to hemolysis. It has been suggested that there are
      clinical manifestations of G6PD deficiency that are related to other tissues, but
      the existence of these is not well documented. Some mutations that produce G6PD
      deficiency in red cells exist at polymorphic frequencies. Individuals with such
      mutations seem to have enjoyed a selective advantage because of resistance to
      falciparum malaria. Different mutations, each characteristic of certain
      populations, are found, and have been characterized at the deoxyribonucleic acid
      (DNA) level. G6PD A-(202A376G) is the most common African mutation. G6PD
      Mediterranean(563T) is found in Southern Europe, the Middle East and in the
      Indian subcontinent. Several other mutations are common in Asia. Genetic
      variability of G6PD has played an important role in the understanding of a
      variety of developmental processes.

PMID- 8861279
TI  - Diagnosis and therapy of acute intermittent porphyria.
AB  - The porphyrias are a group of disorders caused by deficiencies in the activities
      of the enzymes of the heme biosynthetic pathway. As a result, abnormally elevated
      levels of porphyrins and/or their precursors, e.g. delta-aminolevulinic acid and
      porphobilinogen are produced in excess, accumulate in tissues, and are excreted
      in urine and stool. Two cardinal symptoms of the porphyrias are cutaneous
      photosensitivity and neurologic disturbances. Acute intermittent porphyria is the
      most important form of hepatic porphyria because of its frequency and severe
      clinical symptoms.

PMID- 8861280
TI  - Patterns of ACTH secretagog secretion in response to psychological stimuli.

PMID- 8861281
TI  - Infusions of lidocaine into the amygdala, but not the preoptic area, block
      pseudopregnancy in the rat.
AB  - In the rat, vaginocervical stimulation (VCS) received during mating is required
      for the subsequent expression of 10-12 days of twice-daily prolactin surges that
      are necessary for pregnancy or pseudopregnancy (PSP). This temporal separation of
      sensory stimulus and neuroendocrine response suggests that a mnemonic of the
      vaginocervical stimulation is created in the brain that triggers and sustains the
      daily prolactin surges. We investigated the possible involvement of the medial
      preoptic area (mPOA) and the medial amygdala (mAMYG) as potential neural sites
      involved in the processing of this neuroendocrine arc. Cycling female rats were
      bilaterally implanted with intracerebral cannulae in either the mPOA or mAMYG. On
      proestrus, females were manually palpated to confirm sexual receptivity and then
      received bilateral infusions of either the local anesthetic lidocaine, the Ca(++)
      channel blocker, verapamil, or phosphate-buffered saline (PBS) into either brain
      site before or both before and after receipt of 15 intromissions from an
      experienced male. Unmated control females received comparable infusions of
      lidocaine or verapamil, and were placed in the empty test arena for 10 min.
      Infusions consisted of either a single bilateral infusion 15 min before mating
      (Expt. 1), bilateral infusions both 15 min before and after mating (Expt. 2) or
      eight bilateral infusions separated by 30 min intervals spanning a period
      beginning 45 min before and ending 2 h 45 min after mating (Expt. 3). None of the
      lidocaine infusions into the mPOA prevented the establishment of PSP, and neither
      verapamil infusions into the mAMYG nor the shorter-term neural block (i.e. single
      or double lidocaine infusions) of the mAMYG prevented mating-induced PSP.
      However, the longer-term neural block (i.e. multiple lidocaine infusions) of the
      mAMYG significantly reduced the incidence of PSP. These data support previous
      findings that the mAMYG receives sensory input from VCS, and suggest that the
      mAMYG is a site at which a mnemonic of VCS is established.

PMID- 8861282
TI  - A rapid suppressive effect of estrogen in the paraventricular nucleus on
      pulsatile LH release in fasting-ovariectomized rats.
AB  - The paraventricular nucleus (PVN) and A2 are novel estrogen feedback sites where
      estrogen may modulate the neural response to adrenergic inputs during fasting. In
      the present study, the effects of local estradiol (E(2)) perfusion through a
      microdialysis probe placed in the PVN or A2 on pulsatile luteinizing hormone (LH)
      secretion and on norepinephrine (NE) release in the PVN were examined in 48-h
      fasting ovariectomized (OVX) rats to determine whether local estrogen
      administered in the PVN or A2 rapidly inhibits LH secretion during fasting and
      whether this inhibition is mediated by an increase of NE release in the PVN. Five
      days after ovariectomy, animals (n=5 per group) stereotaxically implanted with a
      guide cannula for microdialysis in the PVN (experiment 1) or both PVN and A2
      (experiment 2) were deprived of food for 48 h. Blood samples and dialysates were
      then collected every 6 min for 3 h and every 12 min (experiment 1) or 20 min
      (experiment 2) for 3 h, respectively. The PVN or A2 was perfused with E(2) (5
      ng/ml in artificial cerebrospinal fluid) through a microdialysis probe after the
      first hour of sampling. E(2) perfusion in the PVN caused a rapid and significant
      suppression of mean plasma LH levels and LH pulse frequency in fasting rats but
      no changes in unfasting animals. NE release in the PVN was not affected by the
      local E(2) perfusion of the PVN in either fasting or unfasting groups. This
      perfusion in A2, however, did not cause any apparent changes in plasma LH and
      perfusate NE levels in the PVN and A2. The present results indicate that estrogen
      feedback action at the PVN suppresses LH secretion rapidly during fasting and
      does not involve an increase of NE release in the PVN.

PMID- 8861283
TI  - Dynamic changes in gonadotropin releasing hormone receptor mRNA content in the
      mediobasal hypothalamus during the rat estrous cycle.
AB  - The purpose of the present study was to determine if GnRH receptor mRNA levels in
      the rat brain undergo changes during the estrous cycle. We focused on the arcuate
      and ventromedial nuclei of the hypothalamus and on the hippocampus which are
      sites in the rat central nervous system that have been shown to contain
      measurable amounts of GnRH receptor mRNA. Groups of regularly cycling female rats
      were decapitated at 08.00 and 17.00 h of each day of the estrous cycle, trunk
      blood was collected for radioimmunoassay analysis of circulating LH levels, and
      the brains were processed for 'in situ' hybridization. A cDNA probe encoding the
      rat pituitary GnRH receptor was transcribed 'in vitro' in the presence of (33)P
      alpha UTP and used under saturating conditions to label GnRH receptor mRNA. The
      results show that in the arcuate and ventromedial nuclei GnRH receptor mRNA
      levels are relatively high during diestrus 1, they decline slightly during
      diestrus 2 before they rise to the highest levels at 08.00 h of proestrus. By
      17.00 h of proestrus, GnRH receptor mRNA levels had declined to the lowest levels
      of the estrous cycle where they remain through the morning of estrus. The GnRH
      receptor mRNA levels rise again sharply during the afternoon of estrus. The
      changes in the hippocampus follow a similar pattern in that a decline in GnRH
      receptor mRNA levels to its lowest levels occurs between 08.00 and 17.00 h of
      proestrus. However, the changes in the hippocampus did not reach statistical
      significance. It is concluded that GnRH receptor mRNA levels in the arcuate and
      ventromedial nuclei are upregulated in the morning of proestrus, probably by
      rising estradiol levels, in preparation for the GnRH-LH preovulatory surge while
      this effect of estradiol is not apparent in the hippocampus.

PMID- 8861284
TI  - Reduced NPY induced feeding in diabetic but not steroid-treated rats: lack of
      evidence for changes in receptor number or affinity.
AB  - Concentrations of the potent hypothalamic appetite stimulating peptide
      neuropeptide Y (NPY), and its mRNA, are increased in rats with experimental
      diabetes, suggesting a role in the hyperphagia of this disorder. The 2-h feeding
      responses to intracerebroventricular (i.c.v.) injection of neuropeptide Y (NPY)
      (5, 10, and 15 mu g doses) were measured in male Wistar rats treated with
      streptozotocin (55 mg/kg) to induce diabetes. Streptozotocin-diabetic rats given
      i.c.v. NPY exhibited reduced feeding responses compared to controls (P < 0.05).
      Dexamethasone treated rats exhibit similar changes in NPY content and mRNA in the
      hypothalamus to those seen in diabetes, but are not hyperphagic. Feeding
      responses were also measured in this model, to assess whether high levels of
      endogenous NPY might account for the reduced response in diabetes. In contrast,
      the feeding response to NPY in comparison to controls was unaltered in
      dexamethasone treated rats. To investigate whether altered NPY receptor number or
      affinity, was the underlying mechanism for these divergent responses, receptor
      binding experiments were performed using (125)I-PYY and membranes prepared from
      rat hypothalamus. No significant difference was found in receptor number or
      affinity between the 2 groups (B(max): 114.7 +/- 18.9 vs 127.4 +/- 27.1 fmol/mg
      protein, K(d): 99.6 +/- 28.2 vs 135.1 +/- 32.4 pM). Similarly no difference was
      found between hypothalamic membranes prepared from dexamethasone-treated and
      control animals. NPY receptor subtypes in the hypothalamus were compared with
      that of cortex (predominantly Y1) and hippocampus (predominantly Y2) using the Y1
      specific ligand [Leu(31)Pro(34)] NPY. These studies showed that the binding
      profile in the hypothalamus most closely matched that in the hippocampus,
      suggesting that the majority of hypothalamic receptors were of the Y2 subtype.
      Receptor autoradiography revealed low binding in the hypothalamus, and
      particularly in the paraventricular nucleus of the hypothalamus. Competition with
      [Leu(31)Pro(34)] NPY confirmed that only a low density of binding to Y1 like
      receptors was present in the hypothalamus. No difference was observed between
      control and streptozotocin treated animals. The feeding response to exogenous NPY
      is reduced in experimental diabetes, but not in dexamethasone treated rats. These
      differing responses do not appear to be due to altered NPY receptor number or
      affinity in the hypothalamus.

PMID- 8861285
TI  - Expression of fos-like immunoreactivity in the hypothalamus of the ring dove
      (Streptopelia risoria) at the onset of incubation.
AB  - Fos immunocytochemistry was used in the ring dove (Streptopelia risoria) to
      identify areas in the forebrain and hypothalamus which might be involved in the
      expression of incubation behaviour and the associated changes in neuroendocrine
      function. In this species, both sexes participate in incubation which becomes
      fully established after laying the second egg in the two egg clutch. The eggs
      hatch after 14-15 days incubation. Observations were made in both sexes 16-18 h
      after laying the first egg, 3-5 h after laying the second egg, and after 12-14
      days of incubation. Non-breeding birds were used as controls. Fos-labelled cells
      were observed in several forebrain areas in both sexes irrespective of
      reproductive status but their numbers did not change during incubation. In the
      hypothalamus, very few fos-labelled cells were seen in non-breeding birds but
      appeared in both sexes in the nucleus preopticus medialis after egg laying and
      after 12-14 days of incubation. Fos-labelled cells also appeared in the nucleus
      tuberis (=arcuate nucleus) in both sexes after laying the first or second egg and
      less abundantly, after 12-14 days incubation. Additionally, in males only, fos
      labelled cells were seen after the laying of the first and second eggs in the
      rostral area of the nucleus tuberis close to the walls of the third ventricle.
      These observations suggest that the fos-labelled cells in the nucleus preopticus
      medialis may be involved in the expression of incubation behaviour while those in
      the nucleus tuberis may be involved in the regulation of gonadotrophin or
      prolactin secretion.

PMID- 8861286
TI  - Decrease of endogenous vasopressin release necessary for expression of the
      circadian rise in plasma corticosterone: a reverse microdialysis study.
AB  - The mammalian suprachiasmatic nuclei (SCN) contain an endogenous pacemaker that
      generates daily rhythms in behavior and secretion of hormones. Previously we
      hypothesized that the SCN imposes its circadian rhythm on the rest of the brain
      through a rhythmic release of its transmitters in its target areas. In the
      present study we employed microdialysis-mediated intracerebral administration of
      vasopressin (VP) and its V(1) -antagonist to study the mechanisms underlying the
      circadian control of the release of the adrenal hormone corticosterone. Stress
      free application of the VP V(1) -antagonist in the dorsomedial hypothalamus of
      freely moving, undisturbed animals during the middle of the light period (i.e.
      the trough of the corticosterone rhythm) caused an immediate increase of
      circulating plasma corticosterone levels. A similar administration of VP at the
      end of the light period completely prevented the diurnal rise in plasma
      corticosterone. These results indicate a pronounced inhibitory role for SCN
      derived VP at the level of the dorsomedial hypothalamus with respect to the
      activity of the hypothalamo-pituitary-adrenal axis during the day period. Thus,
      the daily decline in VP release sets a specific time window for the occurrence of
      the daily corticosterone peak. On the other hand, during the dark period
      corticosterone levels are decreasing together with basal VP levels. Therefore, in
      addition to the inhibitory VP signal from the SCN, there is also the need for an
      excitatory SCN signal in order to accomplish the complete circadian profile of
      plasma corticosterone.

PMID- 8861287
TI  - GHRP6-stimulated hormone secretion in somatotrophs: involvement of intracellular
      and extracellular calcium sources.
AB  - GHRP6 is a synthetic hexapeptide which stimulates growth hormone (GH) secretion
      from the pituitary in vivo and in vitro. We have previously shown that in
      identified somatotrophs, GHRP6 induces a biphasic increase in cytosolic Ca2+
      concentration ([Ca2+]i) consisting of an abrupt increase (first phase) followed
      by a sustained plateau of elevated [Ca2+]i (second phase). The first phase
      corresponds to mobilization of intracellular Ca2+ pools and the second phase to
      influx of extracellular Ca2+ ions through voltage-sensitive Ca2+ channels. In
      these experiments, we investigated the specific role of each of these two phases
      in the hormone response to GHRP6. We found that inhibition by thapsigargin of the
      intracellular Ca2+ mobilization phase significantly inhibited the hormone
      response to the peptide during 30 min incubations. Inhibition of the
      extracellular Ca2+ influx phase by nifedipine, a blocker of voltage-sensitive
      Ca2+ channels, resulted in a 53 percent reduction of the secretory response to
      10(-5)M GHRP6. Antagonism of PKC by phloretin, a flavonoid which prevents PKC
      activation, and PKC depletion induced by a 24 h treatment with 10(-6)M PMA,
      completely inhibited the response to GHRP6. Somatostatin, which also inhibits the
      second phase of the Ca2+ response, suppressed the secretory response to GHRP6. We
      conclude that, Ca2+ is the main second messenger and both Ca2+ mobilization and
      Ca2+ entry play a role in the response to GHRP6. However, experiments with PKC
      depletion and SRIF suggest that other messengers are implicated in GHRP6
      signalling in somatotrophs.

PMID- 8861288
TI  - Adrenocorticotrophin and luteinizing hormone responses to N-methyl-D-aspartate
      during fetal development in sheep.
AB  - The hypothalamic mechanisms which underlie the development of the fetal
      neuroendocrine system are unclear. However, in adult animals neuroactive amino
      acids, particularly those acting at the N-methyl-D-aspartate (NMDA) receptor,
      have been shown to be important transmitters involved in the neuroendocrine
      regulation of the anterior pituitary gland. In this study we have investigated
      the potential role of NMDA in the neuroendocrine regulation of fetal pituitary
      function, by examining the ontogeny of LH and ACTH responses to NMDA during fetal
      development in sheep. Catheterized fetal sheep were injected with 3 intravenous
      doses of NMDA (1, 2 and 4 mg/kg; estimated fetal body weight) and saline vehicle
      on consecutive days between days 110-115, 120-125 and 135-140 gestation (term =
      145 days). At each gestational age fetuses also received a pituitary challenge
      test consisting of CRF (0.4 mu g/kg), AVP (80 ng/kg) and GnRH (125 ng/kg). NMDA
      caused a significant dose-related increase in ACTH at day 120-125 (P<0.02) and
      day 135-140 gestation (P<0.001). NMDA had no effect on ACTH secretion at day 110
      115. The ACTH response to the highest does of NMDA (4 mg/kg) increased with
      advancing gestational age, in contrast to the ACTH response to CRF+AVP which was
      the same at all ages. NMDA caused a significant increase in LH secretion at all
      gestational ages with the greatest response observed at the latest gestational
      age studied (day 135-140). A similar increase in LH response to the GnRH
      challenge was observed late in gestation. Pretreatment of fetuses with the
      competitive NMDA antagonist CGP37849 (1 mg/kg) abolished the LH and ACTH
      responses to an intravenous injection of NMDA (4 mg/kg) given 5 min later. These
      data show that activation of NMDA receptors during fetal development elicits the
      secretion of ACTH and LH and demonstrate that NMDA receptors are functionally
      coupled to the neuroendocrine pathways regulating these two hormones during fetal
      life. The dramatic increase in ACTH response to NMDA during the final days before
      birth occurs at a time of high adrenocortical activity and suggests an important
      functional role for these receptors at this time.

PMID- 8861289
TI  - The future of oral and maxillofacial surgery in the UK: the trainees'
      perspective.

PMID- 8861290
TI  - Current principles in microsurgical nerve repair.
AB  - Micronerve reconstruction of motor and sensitive nerves in the head and neck area
      currently has an established range of indications. Surgical procedures always
      follow a strict order, beginning with external neurolysis. In cases of complete
      separation of the nerve stumps or when tensionless coaptation of nerve ends can
      not be achieved, nerve grafts from suitable donor sites, for example the sural
      nerve, have to be interposed. Good functional results can be obtained following
      reconstruction of motor nerves, as with the accessory or the facial nerve. In
      contrast, reconstruction of sensory nerves has a lower success rate but very
      often leads to a subjective improvement of symptoms for the patient. In long
      standing facial palsy with atrophy of the facial musculature, neurovascularly
      reanastomosed muscle grafts offer a good option.

PMID- 8861291
TI  - Craniosynostosis in babies: complications and management of 40 cases.
AB  - Forty consecutive craniofacial cases in babies operated on in a district general
      hospital by a craniofacial team consisting of maxillofacial and neurosurgeons are
      reviewed with regard to diagnosis, surgical treatment, complications and outcome.
      Surgery achieved the release of craniosynostosis and the treatment protocol, and
      perioperative complications are discussed. Dural breaches occurred on four
      occasions with no postoperative sequelae. Blood transfusion was required in all
      cases with an average replacement of 36 percent estimated blood volume (EBV). No
      central nervous system complications occurred but in one case a brachial plexus
      haematoma resulted in a temporary neuropraxia to the shoulder. No major
      infections or deaths occurred in this series.

PMID- 8861292
TI  - Hepatitis C virus in saliva of haemophiliac patients attending an oral surgery
      unit.
AB  - This study determined the frequency with which hepatitis C virus (HCV) could be
      detected in the saliva of 21 HCV-seropositive haemophiliac patients attending an
      Oral Surgery Unit. All sera were positive for HCV RNA by the polymerase chain
      reaction (PCR). Six of the patients were also HIV antibody positive. Saliva was
      collected both by spitting into a Universal container (whole saliva), and by
      means of Salivettes. Following RNA extraction from saliva specimens and synthesis
      of cDNA, nested PCR was performed. Amplified DNA was detected by agarose gel
      electrophoresis and ethidium bromide staining. Overall, HCV was detected in
      saliva from 10 of the subjects (8 HIV seronegative and 2 HIV seropositive) but
      there was not complete concordance between the Salivette specimens and normal
      whole saliva. Analysis of pellet and supernate fractions from whole saliva
      produced similar discrepancies. Repeat runs of PCR for HCV following freezing and
      thawing of the initially positive saliva specimens were unsuccessful. It was
      concluded that HCV is present in the saliva of some haemophiliac patients.
      However, careful optimisation of sample handling and storage methods and of PCR
      technique are required before the true prevalence of HCV shedding in saliva can
      be determined.

PMID- 8861293
TI  - Mandibular fracture osteosynthesis: a comparison of three techniques.
AB  - The authors report on a retrospective study of 205 consecutive patients at the
      Maxillofacial Unit of The Royal Melbourne Hospital to assess if adherence to
      Champy's principles in placement of miniplates in mandibular fractures minimises
      morbidity. 205 well documented cases of mandibular fractures treated with
      internal fixation, January 1985 to April 1990 were studied. The patients were
      assigned into three groups according to the type of fixation; 83 patients had
      miniplate fixation according to Champy's principles, 40 patients had miniplate
      fixation ignoring Champy's principles, 82 patients had transosseous wire (TOW)
      fixation. Outcome was measured by preoperative variables (age, gender, mechanism
      of fracture, site and number of fractures, nerve function, associated injuries
      and treatment delay) and postoperative variables (duration of admission, duration
      of intermaxillary fixation (IMF), malocclusion, infection, dehiscence, union,
      removal of fixation and nerve function which were assessed and compared. The
      results show that the preoperative variables were statistically similar in all
      groups. The postoperative variables indicated a statistically higher complication
      rate for the transosseous wire group compared with the miniplate groups, and
      morbidity was reduced in the group following Champy's principles. The morbidity
      rates in this study compare favourably with other studies even though the
      patients in this study had a much higher incidence of multiple fractures.
      Titanium miniplates appear as effective as miniplates constructed of other
      materials used in previous studies, especially when Champy's principles are
      followed.

PMID- 8861294
TI  - Acquired anterior open bite and facial arthromyalgia: possible aetiology.
AB  - The development of an anterior open bite in four patients with facial
      arthromyalgia is described. There were radiological signs of condylar erosion in
      three of these cases. It is proposed that the pre-senile destructive arthropathy
      of the temporomandibular joint, seen in a small proportion of patients with
      facial arthromyalgia, results from lysis of articular cartilage and bone,
      secondary to an inflammatory process initiated by the local release of
      neuropeptides. Occlusal changes, including anterior open bite, may occur if the
      destructive arthropathy is severe and outstrips dentoalveolar compensation.

PMID- 8861295
TI  - A clinical follow-up study of 278 autotransplanted teeth.
AB  - This open study was undertaken to investigate the outcome of autotransplanted
      teeth over a 6-year period. The subjects were 296 patients who underwent
      autotransplantation in the 6-year period September 1986-August 1992 and outcome
      was measured by considering root formation, occlusion, endodontal and periodontal
      complications. 18 patients were excluded because of inadequate notes or
      radiographs (n = 3) or because they were lost to follow-up (n = 15). The groups
      were divided into open apex and closed apex, and duration of follow up was 6
      months-5 years. Aplasia was the indication for operation in 158 (77 percent) of
      the open apex group but only 10 (14 percent) of the closed apex group, whereas
      caries and associated disease was the most common in the latter (n = 45, 61
      percent compared with 20, 10 percent). There were 24 complete failures, 12 in
      each group (p <0.01). Only 7 teeth in total developed full roots, and 159 showed
      incomplete growth. In the open apex group 112 teeth were in occlusal contact and
      4 were extracted for severe infraocclusion. In the closed apex group there were
      10 cases of mild infraocclusion, none of which required treatment. There were 7
      cases of pulp necrosis in the open apex group, 4 of which required extraction.
      Two teeth in the closed apex group were extracted for endodontic reasons. Only 1
      tooth (in the closed apex group) had to be extracted for periodontal reasons.
      Autotransplantation is a reliable method with a good prognosis for donor teeth
      with both open and closed apexes. The technique is applicable whatever the
      aetiology of the agenesis, and is worthy of consideration should there be a
      suitable donor tooth.

PMID- 8861296
TI  - A clinical and histopathological study of osteoarthrosis of the temporomandibular
      joint.
AB  - OBJECTIVES: The aims of this study were (i) to objectively assess the
      histopathological features in TMJ condylar head specimens to correlate the
      findings with clinical information obtained from pathology request forms and
      hospital notes (ii) to analyse the pre- and post operative investigation and
      management of patients with TMJ-OA. DESIGN: A retrospective histological analysis
      of 136 specimens using a semi-quantitative scoring system. SUBJECTS: 132 patients
      with TMJ-OA in Trent Hospital Region (mean age 34: range 14-71) provided 136
      condylar heads. MAIN OUTCOME MEASURES: 11 histological parameters were assessed.
      The global scores obtained were compared with the clinical data. RESULTS: There
      was no clear correlation between histology and pre- and post-operative clinical
      data. 95% of patients were treated for at least 6 months before surgery and 94%
      had pain before surgery. Postoperatively, the success rate was 58% (35% painfree
      and 23% still in pain but better than before surgery). Non-surgical treatments
      were not used routinely after surgery. Only 62% of the patients were followed up
      for at least one year after surgery. 61% of the patients were reported to have
      macroscopic degenerative changes at surgery whilst all had microscopic OA.
      CONCLUSION: The mean age of patients presenting with TMJ-OA is younger (M = 31/F
      = 34) than in some studies while there is still a female preponderance for the
      disease. Tomograms and arthrograms appear to have a higher specificity than
      orthopantomograms for diagnosing gross degenerative change. There appears to be a
      need for a standardised management protocol.

PMID- 8861298
TI  - Computerised audit systems.

PMID- 8861299
TI  - A rare case of glomus tumour; buccal localization.

PMID- 8861297
TI  - Preformed above elbow cast for composite radial forearm free flap.
AB  - A simple and efficient method of splinting the forearm following harvest of a
      composite radial forearm free flap is presented.

PMID- 8861300
TI  - Chronic infection mimicking antral carcinoma.

PMID- 8861301
TI  - Enlarged palatine tonsil causing paraesthesia to the posterior one-third of the
      tongue.

PMID- 8861302
TI  - The omentum--has it a place in the treatment of spinal cord injury?

PMID- 8861303
TI  - Three cases of hindbrain herniation in adults with comments on some diagnostic
      difficulties.
AB  - In discussing the clinical features and surgical treatment of adult patients with
      Arnold Chiari deformity type I the authors focus on the differential diagnosis
      from demyelinating disease and present three illustrative cases. Out of 118
      patients initially diagnosed as having demyelinating disease and admitted to our
      hospital between December 1991 and April 1993, three were subsequently found to
      have the Arnold Chiari deformity on MRI. The delay until correct diagnosis
      amounted to 10, 16 and 32 years, respectively. Our study stresses the diagnostic
      importance of MRI of the craniocervical area in cases of unexplained neurological
      symptoms and external signs of dysplasia. Accurate examination, early diagnosis
      and selection of proper surgical management can alleviate severe symptoms in many
      instances and prevent neurological complications.

PMID- 8861304
TI  - Magnetic resonance angiography for anterior midline aneurysms.
AB  - Over an 18-month period (June 1993-December 1994), all patients presenting with a
      subarachnoid haemorrhage (SAH) were considered for magnetic resonance angiography
      (MRA) as part of their investigation. Our experience to date leads us to believe
      that anterior midline aneurysms can be confidently and rapidly diagnosed with MRA
      alone without recourse to invasive intra-arterial digital subtraction
      angiography. This assumes, of course, that images can be obtained; some patients
      cannot be investigated by MR because of the presence of metallic foreign bodies;
      in a small proportion without anaesthesia the images will be so degraded as to be
      valueless and some patients will be judged unsuitable from the outset because of
      their clinical state. In 30 patients, a diagnosis of an anterior midline aneurysm
      was made on MRA and 21 of these patients underwent surgery on the MR images
      alone. Surgery, undertaken via a midline approach in these 21 patients, confirmed
      the MR findings.

PMID- 8861305
TI  - Modification of the standard pterional approach for aneurysms of the anterior
      circle of Willis.
AB  - A modification of the standard pterional approach for aneurysms of the anterior
      circulation is described. Our technique utilizes a smaller curvilinear skin
      incision, splitting the temporalis and a limited craniectomy. Reduced tissue
      dissection results in a smoother postoperative course and improves cosmesis
      without compromising neurological recovery. Minimal brain retraction is required
      as the technique allows the surgeon to make full use of the basal opening without
      temporalis muscle obscuring the view.

PMID- 8861306
TI  - Microsurgery with the Steiner-Lindquist stereotaxic guide.
AB  - The Steiner-Lindquist microsurgical stereotaxic guide was used for operations for
      intra-axial lesions in 15 patients. The lesions were identified by stereotaxic CT
      or MRI and stereotactic co-ordinates were then calculated and set for the guiding
      laser beam. The beam was used for planning the craniotomy and its path followed
      during the microsurgical dissection, until the lesion was reached. Seven lesions
      were situated in eloquent areas of the brain and could not have been safely
      attacked without the aid of stereotaxic localization. Five of these and two other
      lesions were quite small, and would have been difficult to find without
      jeopardizing normal brain structures. For the remaining lesions the stereotaxic
      laser guide was facilitatory, but not indispensible. Radical removal was achieved
      in 11 of the 15 lesions. The Steiner-Lindquist microsurgical guide incorporates
      the freedom of standard microsurgical techniques with the safety of operating in
      a stereotaxically defined space.

PMID- 8861307
TI  - Ultrasound-guided neurosurgery: a feasibility study in the 3-30 MHz frequency
      range.
AB  - This study, which includes seven patients, illustrates some potential values of
      the interactive use of ultrasound technology prior to, during and after brain
      tumour resection. Ultrasound B-scan and colour flow imaging were applied during
      open surgery using a cardiac scanner in the 3.25-7.5 MHz frequency range and an
      intravascular scanner with catheters at 10, 20 and 30 MHz. The tumour and vital
      blood vessels were localized prior to resection using low frequency imaging from
      the brain surface. High frequency, high resolution close-up imaging was applied
      during and after resection in order to identify remaining tumour tissue, as well
      as to detect blood vessels in the vicinity of the resection wall. The study also
      demonstrates that the tumour and surgical tools such as, for example, bipolar
      diathermy, acoustic aspirator or biopsy forceps,can be visualized simultaneously.
      This simplifies the localization of remaining tumour tissue.

PMID- 8861308
TI  - Radiosurgery: a minimally interventional alternative to microsurgery in the
      management of acoustic neuroma.
AB  - We report the results of treatment with radiosurgery of 29 tumours in 27 patients
      with acoustic neuromas between 1986 and 1989. The median follow-up was 6.6 years.
      The treatment appears to be an effective alternative to surgery for patients with
      tumours of 3 cm diameter or less. The mortality and morbidity of the treatment
      and the presentation of cranial nerve function is comparable to the very best
      surgical results. Every patient with an acoustic neuroma should be informed about
      this alternative to direct surgery.

PMID- 8861309
TI  - MRI confirmation of accuracy of freehand placement of mesial temporal lobe depth
      electrodes in the investigation of intractable epilepsy.
AB  - Stereotactic techniques are commonly used to place intracerebral depth
      electrodes. We placed 15 depth electrodes (9R, 6L) freehand, orthogonally into
      temporal lobes in 12 patients undergoing monitoring with subdural strip
      electrodes in the evaluation of their intractable epilepsy. Coronal MRI was
      performed with the electrodes in place. The mean distance from the closest depth
      electrode contact to the hippocampus was 0.8 mm (range 0-5 mm). In 11 instances
      the closest contact was either within or making contact with the hippocampus, and
      in another three it was within 3 mm. For 13 electrodes, the most distal contact
      was the closest to the hippocampus, for two the penultimate contact was closest.
      There were no complications from electrode placement. Ictal onset was mesial
      temporal in 11 patients and frontal in one. Temporal onset was detectable in the
      depth electrode in each case, usually simultaneously with the onset in the
      subdural electrode although often the discharge was better developed in the depth
      electrode. We conclude that freehand placement of depth electrodes orthogonally
      into the temporal lobe can achieve a degree of accuracy sufficient to localize
      seizure onset in the mesial temporal lobe.

PMID- 8861310
TI  - Moyamoya disease in patients of Finno-Ugric origin.
AB  - The terms moyamoya disease, moyamoya syndrome and moyamoya phenomenon can be
      found dispersed throughout the literature. The diagnostic criteria for moyamoya
      disease are: (1) stenosis or occlusion of the anterior cerebral, middle cerebral
      and internal carotid arteries, (2) an abnormal vascular network near these
      arteries and (3) bilateral findings. When only the two first conditions are
      present, the term moyamoya syndrome is used. The incidence of moyamoya disease is
      high in the Mongol race, although the moyamoya syndrome is more frequently
      reported among Caucasians. In the last two decades 41 cases of moyamoya were
      diagnosed in two Hungarian and two Scandinavian hospitals, respectively. Thirty
      one patients were operated on 12 unilaterally and 19 bilaterally--either with
      extracranial/intracranial bypass (29 cases) or with encephalomyosynangiosis (2
      cases). After a mean follow-up of seven years, 67.7% of the operated cases were
      symptom-free or neurologically improved. The majority of the patients had
      moyamoya disease and turned out to be of Finno-Ugric or Lapplandish ancestry.
      These people originally migrated from the East and belong to the Ural-Altaic
      family. Our findings suggest that while the moyamoya syndrome is found in
      different races, the moyamoya disease may be limited to people of Eastern
      (Mongol) origin. Revascularization surgery may be of benefit to patients with
      moyamoya.

PMID- 8861311
TI  - The value of the Short Form 36 score in the outcome assessment of subarachnoid
      haemorrhage.
AB  - This pilot study aimed to establish if the Short Form 36 (SF-36) provides
      clinically relevant information about patient outcome which is not detected using
      the Glasgow Outcome Score (GOS) A retrospective postal questionnaire survey of
      all patients operated on for subarachnoid haemorrhage at the Leeds General
      Infirmary between March 1991 and December 1992 of perceived health status was
      undertaken 6-18 months following surgery. Of the respondents with a GOS score of
      Good the SF-36 score was reduced in each domain. The most notable score reduction
      was in the role-function physical domain where the mean score was 48 percent
      compared with a population norm of 88 percent. It was concluded that the SF-36
      has a role in the evaluation of patients following surgery for SAH and may have a
      place in their routine assessment. Further work in a larger group of patients is
      required.

PMID- 8861312
TI  - Endoscopic treatment of an unusual multicystic lesion of the brainstem: case
      report.
AB  - We report a 32-year-old woman who presented with headache, mild hemiparesis and
      clumsiness of the right hand. CT and MRI revealed a multicystic formation of the
      brainstem involving the thalamus and midbrain. We inspected the formation
      endoscopically and fenestrated some of the cysts. In one of the cysts we found an
      anomalous vascular nidus. Postoperative MRI revealed reduction of the fenestrated
      cysts. The patient is doing well 13 months after endoscopy and has no
      neurological deficit.

PMID- 8861313
TI  - Testicular embryonal cell carcinoma metastasizing to the site of a previously
      excised cerebellar haemangioblastoma.
AB  - We report a patient with von Hippel-Lindau disease in whom a metastatic embryonal
      cell carcinoma from the testis occurred at exactly the same site from which a
      cerebellar haemangioblastoma had been excised 12 years earlier.

PMID- 8861314
TI  - Posterior inter-body fusion after spinal tumour resection.
AB  - A case is reported where after resection of a large cervical spinal intradural
      schwanomma a direct plate and screw fixation of the adjacent vertebral bodies was
      performed. The issue of instability after spinal tumour resection and the merits
      of the fixation technique described are discussed.

PMID- 8861315
TI  - Spinal meningeal melanocytoma: a case report and review of the literature.
AB  - We present a case of spinal meningeal melanocytoma involving the C5 nerve root
      with spinal cord compression which resembled a neurinoma clinically as well as
      radiologically. The clinical, radiological and pathological features of this and
      11 other cases reported in the literature are reviewed. The significance of
      correct diagnosis and aggressive surgical management of this benign neoplasm is
      emphasized.

PMID- 8861316
TI  - Dumbbell hydatid cyst of the spine.
AB  - We describe a case of dumbbell hydatid cyst of the T(10) pedicle. This cyst had
      both extradural and retroperitoneal components,leading to spinal cord compression
      and abdominal pain. Following surgical excision and irrigation with hypertonic
      saline the patient made a full recovery, and is recurrence-free after 18 months
      follow-up.

PMID- 8861317
TI  - Desmoplastic cerebral glioblastoma of infancy.
AB  - A distinctive glial tumour in an 8-month-old child characterized by superficial
      location, attachment to the dura, desmoplasia and histological malignancy is
      described. The tumour differed from "desmoplastic cerebral astrocytoma of
      infancy" and "desmoplastic infantile ganglioglioma" by virtue of the presence of
      frequent mitoses and necrosis and lack of basal lamina. We have termed this
      tumour a "desmoplastic cerebral glioblastoma of infancy". The differential
      diagnosis and the origin of the desmoplasia are discussed.

PMID- 8861318
TI  - Cerebellar mutism following posterior fossa tumour surgery.
AB  - Two cases of transient mutism following operative removal of cerebellar
      medulloblastoma are reported. These add to the few cases reported in the
      literature of this rare complication of posterior fossa tumour surgery in
      children.

PMID- 8861319
TI  - Neurenteric cyst of the anterior cranial fossa.
AB  - Neurenteric cysts are uncommon developmental cysts of the central nervous system
      lined by epithelium of intestinal origin. We describe a cyst in the anterior
      cranial fossa, which has not been previously reported.

PMID- 8861320
TI  - Interstitial iodine-125 radiosurgery for cerebral metastases.

PMID- 8861342
TI  - Teat thickness changes may provide biological test for effective pulsation.
AB  - Pulsation rates of 40, 60 and 80 cycles/min were combined with pulsator ratios of
      50, 60, 70 or 80 percent in two experiments with different liners. Machine
      induced, short-term changes in teat thickness of 14 cows were compared with milk
      flow rate characteristics and machine strip yields to evaluate the effectiveness
      of pulsation in relation to liner type. Post-milking teat thickness increased
      progressively as the b phase of the pulsation cycle was lengthened, and as the d
      phase was shortened, at all pulsator rates and with either liner. Teat thickness
      values increased significantly (P < 005) when the d phase was < 15%. For ratios
      of 50 and 60% , teat thickness decreased progressively as pulsation rate was
      increased. At the higher ratios, thickness values were lowest at 60 cycles/min.
      Pulsation settings that tended to increase teat thickness values also increased
      both peak milk flow rates and machine strip yields. The influence of liner type
      on teat thickness changes appeared to be at least as important as the influence
      of pulsator ratios and greater than the effect of pulsation rate. If so, then
      international standards for acceptable pulsation characteristics cannot be
      defined solely in terms of pulsator settings. A limit of +/- 5 percent for
      machine-induced changes in thickness of the teat apex would be an additional
      guideline for effectiveness of pulsation in relation to both liner type and
      vacuum level. This could provide a basis for a dynamic test applied to milking
      cows under field conditions.

PMID- 8861343
TI  - Milk yield, oxytocin and beta-endorphin gradually normalize during repeated
      milking in unfamiliar surroundings.
AB  - procedure previously shown to inhibit oxytocin release and milk ejection. Two
      control milkings were performed in familiar surroundings. After milk flow had
      ceased, two i.v. injections of 1 i.u. oxytocin were given to remove the remaining
      milk. Milk flow was recorded continuously and blood samples were taken every
      minute during milking and 10 min after milking. During the first milking in
      unfamiliar surroundings, no oxytocin was released. Thereby, only 13 percent of
      the total milk yield, the cisternal milk, was available and the alveolar milk
      fraction could only be removed after injection of oxytocin. During subsequent
      relocations oxytocin release steadily increased toward the control level,
      although the timing of oxytocin release remained delayed as compared with
      controls. However, the milk fraction available before oxytocin injection
      increased with increasing number of removals, following an asymptotic approach to
      control levels. The concentrations of beta-endorphin, cortisol (and perhaps also
      of prolactin) gradually declined with the number of times the animal was moved to
      unfamiliar surroundings, i.e. hormone concentrations gradually adjusted to
      control level. During milking, concentrations of prolactin and cortisol
      increased, while beta-endorphin concentrations decreased (except for the first
      relocation). We conclude that milking-related oxytocin release and therefore milk
      ejection adapted gradually to repeated relocations to unfamiliar surroundings.
      This adaptation was inversely related to beta-endorphin concentrations, so it is
      possible that oxytocin release was suppressed by high circulating beta-endorphin
      concentrations.

PMID- 8861344
TI  - Simultaneous recording of oxytocin release, milk ejection and milk flow during
      milking of dairy cows with and without prestimulation.
AB  - The effects of manual teat stimulation compared with stimulation by the liner of
      a conventional milking machine and the influence of milk ejection on the course
      of milk flow during the entire milking were investigated. Twelve cows were milked
      with or without prestimulation on three quarters and milk flow was recorded while
      intramammary pressure (IMP) was recorded in the left front quarter and blood
      samples for the determination of oxytocin (OT) were taken at 1 min intervals. OT
      concentrations increased very similarly in response to manual teat stimulation or
      liner stimulation and remained elevated during the entire milking procedure. Milk
      flow curves were generally bimodal without stimulation and not bimodal during
      milking after prestimulation. Milk yield was not significantly lower in milkings
      without than with stimulation, whereas machine-on time was prolonged and peak
      milk flow rate was reduced during milking without stimulation. Time to reach milk
      flow plateau, time to reach peak flow rate and IMP profiles were similar in both
      treatments if time was calculated from the start of stimulation. IMP increased
      similarly in response to manual or liner teat stimulation. In milkings with and
      without prestimulation IMP did not reach its maximum until the start of milking.
      In bimodal milk flow curves the second increase of milk flow occurred
      concomitantly with the start of IMP increase; ejection IMP generally occurred
      concomitantly with the milk flow plateau. In some cases during milking without
      prestimulation only small and transient CT release was observed. In response, IMP
      did not increase to its maximum and increased further in response to a stripping
      related CT release. During the course of milking IMP decreased slightly because
      of the emptying of the three milked quarters. After the end of milking, and with
      CT concentrations decreasing to the premilking values, IMP again decreased
      slightly to another plateau, probably owing to myoepithelial relaxation. Thus the
      course of milk ejection, i.e. the IMP profile, influenced milk removal markedly
      during early milking.

PMID- 8861345
TI  - Leucine and protein metabolism in the lactating dairy cow mammary gland:
      responses to supplemental dietary crude protein intake.
AB  - Mammary gland protein metabolism, determined by an arteriovenous difference
      technique, was monitored in four Holstein-Friesian dairy cows in response to
      supplemental dietary protein (provided as rumen-protected soyabean meal) during
      late lactation (weeks 24-30). Each cow was offered two isoenergetic diets
      composed of grass silage (170 g crude protein/kg dry matter) plus either a low
      (108 g/kg) or medium (151 g/kg) crude protein concentrate in a single crossover
      design involving two 21 d periods. On day 21, arteriovenous measurements across
      the mammary gland were made during a 13 h continuous i.v. infusion of [1
      (13)C]leucine and with frequent (2 hourly) milk sampling during the final 6 h.
      Although total milk yield was slightly increased (+1 kg/d) by protein
      supplementation, milk protein yield was not significantly affected. Whole body
      protein flux (protein synthesis plus oxidation) was not significantly affected by
      supplementation. Total mammary gland protein synthesis (milk plus non-milk
      protein) was also not affected by supplementation but on both diets gland
      synthesis was always greater (by 20-59 percent) than milk protein output. The
      fractional oxidation rate of leucine by the mammary gland was significantly
      increased by protein supplementation (0-047 v. 0-136). Although the enrichment of
      leucine in secreted milk protein continued to increase, the final value (at 13 h)
      was 0-94 of the arterial plasma free leucine plateau value (not significantly
      different), suggesting almost exclusive use of plasma free leucine for milk
      protein synthesis. Based on current feeding schemes for dairy cattle, a fixed
      proportion (0-65 0-75) of the additional protein intake (+490 g/d) should have
      been partitioned into milk protein. Instead, leucine oxidation by the mammary
      gland was increased. Whether oxidation of other amino acids was also enhanced is
      unknown but if amino acid oxidation and the 'additional' non-milk protein
      synthesis occurring in the gland are not crucial to milk synthesis, then by
      reducing such activities improvements in the efficiency of converting absorbed
      amino acid into milk protein can be achieved.

PMID- 8861346
TI  - Detection and localization of peptidases in Lactococcus lactis with monoclonal
      antibodies.
AB  - Monoclonal antibodies against peptidases of Lactococcus lactis were isolated and
      characterized: PEPN1-4 against a lysyl aminopeptidase PepN, PEPT1-5 against a
      tripeptidase PepT and PEPD1-3 against a dipeptidase PepD. These monoclonal
      antibodies reacted specifically with their respective antigens in crude cell
      extracts of Lc. lactis subspp. cremoris and lactis. A number of monoclonal
      antibodies cross reacted with proteins of other (lactic acid) bacteria. PEPT1, 2,
      4 and 5 cross reacted weakly with a 35 kDa protein in Lactobacillus delbrueckii,
      while PEPT1 and PEPT2 reacted with proteins in the cell-free extract of
      Streptococcus thermophilus and Clostridium fervidus. Of the four isolated
      monoclonal antibodies against PEPN, only PEPN3 cross reacted weakly with a 90 kDa
      protein in Escherichia coli cell-free extract, and the other three antibody
      species against PEPN3 cross reacted with 80 kDa proteins of Lb. casei, Lb.
      delbrueckii, and Str. bovis, but not of Esch. coli. Of the three monoclonal
      antibodies against PepD, only PEPD1 and PEPD2 cross reacted with 40 kDa proteins
      of Lb. casei, Lb. delbrueckii and Str. bovis. All PEPN, PEPD and PEPT antibodies
      reacted with components in cell-free extracts of eleven different Lc. lactis
      strains, indicating that the peptidases of these strains were very similar to
      those of Lc. lactis subsp. cremoris WG2. However, Lc. lactis subsp. hordniae
      appeared to differ from the other Lc. lactis subspecies since only PEPT1, 2 and 5
      reacted with a protein in the cell-free extract. Immunogold labelling of Lc.
      lactis WG2 with the isolated monoclonal antibodies revealed that PepN, PepD and
      PepT were located intracellularly. The intracellular location of these peptidases
      is discussed in relation to the supply of essential amino acids and peptides.

PMID- 8861347
TI  - Immunomodulatory activities of whey fractions in efferent prefemoral lymph of
      sheep.
AB  - Studies on the immunomodulatory activities of ruminant milk and colostral whey
      fractions were undertaken. By comparing with boiled colostral whey in a
      preliminary experiment, a putative heat-labile immunostimulatory factor for
      antibody responses was found to be present in ovine colostral whey. Studies were
      then undertaken in sheep in which the efferent prefemoral lymphatic ducts were
      cannulated bilaterally, and immune responses in the node were measured following
      subcutaneous injection in the flank fold of whey protein preparations of various
      purities. A significant sustained decline of efferent lymphocyte output was
      observed following injection with autologous crude milk whey or colostral whey
      preparations, but no changes were observed in interferon-gamma levels in lymph
      plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high
      purity were compared in bilaterally cannulated sheep. A transient decline over
      the first 6 h was seen in the efferent lymphocyte output and lymph flow rate
      after injection of both fractions. A significant difference was seen between the
      two fractions in interferon-gamma levels in lymph at 6 h after injection.
      However, no significant changes in the proportion of the various efferent
      lymphocyte phenotypes were seen following either treatment. Whereas both
      fractions showed a significant inhibitory effect in a dose-dependent manner on
      the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic
      stimulation in vitro, no similar changes were seen following in vivo stimulation
      with these two fractions.

PMID- 8861348
TI  - Effects of somatic cell count and stage of lactation on raw milk composition and
      the yield and quality of Cheddar cheese.
AB  - The effects of somatic cell count and stage of lactation on the yield and quality
      of Cheddar cheese were investigated. Cheese was manufactured in a pilot scale
      factory using milk of low bulk milk cell count (BMCC) from herds in early (LE)
      and late (LL) lactation, and milk of high BMCC from herds in early (HE) and late
      (HL) lactation. The deleterious effect of an elevated BMCC on product yield and
      quality in late lactation was clear. Cheese made from LL milk was significantly
      superior to that made from HL milk for most yield and quality characteristics
      measured. Stage of lactation also affected cheese yield and quality, as evidenced
      by the lower recovery of fat and poorer flavour score for cheese from LL milk
      compared with that manufactured from LE milk. The observed differences could be
      explained largely by differences in raw milk composition. We conclude that the
      effect of stage of lactation was magnified by an elevated BMCC, and that many of
      the problems encountered when processing late season milk could be overcome by
      containing mastitis at this time.

PMID- 8861349
TI  - Cortisol and regulation of tight junctions in the mammary gland of the late
      pregnant goat.

PMID- 8861350
TI  - Recommended method for measuring changes in thickness of the bovine teat with
      spring-loaded calipers.

PMID- 8861351
TI  - PP3 component of bovine milk: a phosphorylated whey glycoprotein.

PMID- 8861391
TI  - Virulence and outer membrane properties of a galU mutant of Klebsiella pneumoniae
      CG43.
AB  - Non-mucoid mutants of a Klebsiella pneumoniae wild type strain CG43 were
      generated by transposon mutagenesis. One of the mutants was incapable of
      fermenting galactose and was designated CG43-17. Alterations of the bacterial
      surface including capsule, lipopolysaccharides, and several species of outer
      membrane proteins were noted. The mutant was avirulent to mice and became highly
      sensitive to human serum. The defects could not be complemented by the gaIETK
      operon. Diminished activity of UDP-glucose pyrophosphorylase in CG43-17 suggested
      that it is a gaIU mutant. This possibility was confirmed because the parental
      phenotypes could be fully restored in the mutant by transforming it with a human
      liver cDNA encoding UDP-glucose pyrophosphorylase.

PMID- 8861392
TI  - Transfer of a pertussis toxin expression locus to isogenic bvg-positive and bvg
      negative strains of Bordetella bronchiseptica using an in vivo technique.
AB  - Bordetella pertussis is the causative agent of whooping cough, a contagious
      childhood respiratory disease, increasing public concern over the safety of
      current whole-cell vaccines has led to decreased immunization rates and a
      subsequent increase in the incidence of the disease. The preparation of safer
      vaccines is at present concentrated on the production of detoxified virulence
      factors such as pertussis toxin (PT) for inclusion in acellular vaccine
      preparations. A permanently avirulent Bordetella bronchiseptica strain was
      previously engineered to constitutively produce PT. An in vivo cloning technique,
      based on the principles of conjugal mating and chromosome transfer was employed
      to transfer the PT expression locus of this strain to virulent and avirulent
      strains of B. bronchiseptica. This transfer was confirmed by Southern
      hybridization. An analysis of PT secretion in isogenic virulent and avirulent
      strains of B. bronchiseptica revealed that the PT produced was cell-associated
      and not secreted to the growth medium. This evidence suggests that B.
      bronchiseptica does not possess functional PT secretion (ptl) genes. Therefore,
      to achieve a PT expression and secretion system suitable for vaccine purposes in
      Bordetella bronchiseptica, functional ptl genes of B. pertussis are also
      required.

PMID- 8861393
TI  - Lateral genetic transfers between group A and G streptococci for M-like genes are
      ongoing.
AB  - Previously we described a long-polymerase chain reaction (PCR) method to amplify
      a 4-7 kb target containing most of the components of the vir regulon (mga, emm
      like genes and scpA) in a number of group A streptococcus (GAS) isolates. In
      contrast to GAS, strains of human group G streptococcus (GGS) gave approximately
      1.6 or 1.8 kb products. Sequence analysis of the amplified products issued from
      GGS templates revealed a mosaic consisting of upstream sequence from mga (the
      gene for positive regulator of vir regulon), an unidentified open reading frame,
      a short segment of emm (the gene for M protein, an antiphagocytic molecule) and
      an upstream sequence of scp (C5a-peptidase gene). A full length scpG is present
      immediately downstream from the mosaic segment in the human GGS genome. The GGS
      PCR fragment did not code for mga or full length emm. All human GGS isolates are
      known to code for emm but the gene is separated from scpG by at least 10 kb. Our
      data, obtained using long-PCR and unrelated strains of GGS, confirm this. We
      could not detect a homologue of mga in human GGS by hybridization analysis. The
      mosaic sequence suggests that enbloc transfer of the vir regulon from GAS to a
      GGS progenitor may have occurred, following which deletion and rearrangement
      events may have taken place. Partial nucleotide sequences of emm corresponding to
      the variable domain of M proteins from three local GGS isolates were determined.
      One sequence (emmGGS6) is 99% identical to emm from a geographically separated
      isolate of GGS recently described.3 emmGGS6 also has significant homology with
      emm from a GAS strain (STDONALD) isolated from the same geographical area as was
      GGS6. The two emm sequences (emmGGS6 and emmSTDONALD) revealed frameshift
      compensatory frameshift mutations relative to each other, contributing to lower
      amino acid homology between the two predicted M proteins. Since emmSTDONALD has
      no known relatives within the 80 or so emm sequences in the database, we
      speculate that it could have been laterally acquired from GGS. Horizontal
      transfers between GGS and GAS may be ongoing.

PMID- 8861394
TI  - Inhibition of the multiplication of Listeria monocytogenes in a murine hepatocyte
      cell line (ATCC TIB73) by IFN-gamma and TNF-alpha.
AB  - The effects of IFN-gamma and TNF-alpha on intracellular multiplication of
      Listeria monocytogenes in a murine enbryonic hepatocyte cell line (ATCC TIB 73)
      were investigated. Neither IFN-gamma nor TNF-alpha alone (10, 25, or 100 ng/ml)
      significantly inhibited intracellular multiplication of L. monocytogenes. In
      contrast, addition of both IFN-gamma and TNF-alpha (10, 25, or 100 ng/ml)
      significantly inhibited intracellular listerial multiplication. The anti
      listerial effects of IFN-gamma and TNF-alpha were not blocked by adding
      aminoguanidine or catalase. Nor did IFN-gamma and TNF-alpha treated hepatocyte
      monolayers produce detectable amounts of nitric oxide or hydrogen peroxide. These
      findings suggest that the effects of IFN-gamma and TNF-alpha may be independent
      of reactive oxygen (ROI) and nitrogen (RNI) intermediates.

PMID- 8861395
TI  - Pneumococcal cell wall activates NF-kappa B in human monocytes: aspects distinct
      from endotoxin.
AB  - The transcription factor NF-kappa B plays a central role in inflammation by
      controlling the transcription of multiple genes which participate in the acute
      phase response. Mice with a targeted disruption of the p50 subunit of NF-kappa B
      are hyper-susceptible to challenge with pneumococci but not endotoxin. We sought
      to clarify the role of NF-kappa B in the host response to the critical
      inflammatory component of pneumococci, the cell wall. Activation of NF-kappa B
      was monitored by expression of luciferase from cells transfected with an NF-kappa
      B dependent luciferase reporter construct. 70Z/3 murine pre-B cells and U937
      human monocytes failed to produce luciferase in response to 10(7) pneumococci or
      10 mu g cell wall; strong responses were obtained with lO mu g of LPS. In
      contrast, THP-1 human monocytes showed strong luciferase production with all
      three stimuli: LPS, intact pneumococci and cell wall. The response was time and
      dose dependent. Cell wall activity was retained despite alteration of the choline
      of the teichoic acid or protease treatment suggesting the glycopeptide backbone
      to be a critical determinant of bioactivity. We conclude that activation of NF
      kappa B by pneumococci is restricted to certain cells and that this
      proinflammatory activity may be a specific feature of the pneumococcal cell wall
      glycopeptide backbone.

PMID- 8861396
TI  - Craving despite extremely high methadone dosage.
AB  - A clinical case study is presented of an opiate addict, currently under methadone
      maintenance treatment (MMT), who claims the need of a higher daily methadone
      dose. He is admitted to a closed metabolic ward, where he receives 250 mg
      methadone per day. During 24 h both pharmacokinetic parameters and craving levels
      are measured simultaneously. Results show extremely high methadone concentrations
      and its primary metabolite EDDP in plasma and urine. The craving level shows a
      distinguished peak around the methadone administration on both measured days.
      Withdrawal symptoms as well as self-reported craving did not correspond at all to
      the extremely high methadone concentration level in plasma. So we suggest that in
      individual cases if high methadone doses and plasma methadone levels are not able
      to diminish craving symptoms, dose adjustment should be accompanied by education
      regarding daily anticipatory increase of opiate craving.

PMID- 8861397
TI  - A comparison of cocaine-dependent cigarette smokers and non-smokers on
      demographic, drug use and other characteristics.
AB  - Cigarette smoking (n = 156) and non-smoking (n = 43) individuals seeking out
      patient treatment for cocaine-dependence were compared on demographic, drug use
      and other variables. Smokers were younger, less educated, earned less money,
      began cocaine use at an earlier age, used cocaine more frequently, were more
      likely to inject or smoke cocaine, were more likely to report legal troubles and
      having harmed someone physically as consequences of their cocaine use, and had
      more severe employment and legal problems than non-smokers as measured by the
      Addiction Severity Index. Smoking remained a significant predictor of more
      frequent cocaine use, using more grams of cocaine per week and using cocaine via
      an injection or smoking route even after adjusting for demographic differences
      between smokers and non-smokers via regression analyses. Smoking status was not
      significantly related to treatment outcome. Overall, these results indicate that
      cocaine-dependent smokers represent a more high-risk group than non-smokers. This
      relationship between smoking, cocaine use, and associated problems merits further
      investigation.

PMID- 8861398
TI  - Pattern shift visual evoked potentials in abstinent cocaine-dependent, alcohol
      dependent, and cross-dependent patients.
AB  - The present study evaluated pattern shift visual evoked potential (VEP)
      amplitudes and latencies in four groups of adult subjects, characterized by the
      presence/absence of a recent history of alcohol dependence factorially crossed
      with the presence/absence of a recent history of cocaine dependence. All of the
      subjects were healthy and uncomplicated by histories of serious head injury,
      seizures (including drug-related seizures), and major medical, neurological, or
      psychiatric disorders. The subjects comprising the three patient groups were
      evaluated after 1 - 5 months of verified abstinence. Analyses of VEPs evoked by
      checkerboard reversal indicated a main effect of previous cocaine dependence on
      P100 latency. No main effect of previous alcohol dependence and no alcohol by
      cocaine dependence interaction were detected. The increased P100 latencies
      detected in abstinent, cocaine-dependent subjects are most likely related to
      cerebrovascular and neurological effects of chronic cocaine use.

PMID- 8861399
TI  - Treatment needs and experiences of Australian women with alcohol and other drug
      problems.
AB  - Two hundred and sixty-seven women were interviewed as part of a national survey
      examining the treatment needs and experiences of Australian women who had
      received assistance for their alcohol and other drug problems. The majority of
      women had previously received assistance for their substance use, and of these
      most had left alcohol and other drug treatment programs before completion. While
      the women cited a number of ways in which they were helped by such services,
      several areas were identified by the women as important and amenable to
      improvement. Among the service issues raised were access, models of service
      delivery, service structure and staffing, physical environment, physical and
      psychological safety and the handling of issues such as health status and sexual
      assault.

PMID- 8861400
TI  - Beliefs about steroids: user vs. non-user comparisons.
AB  - The differences in beliefs about the effects of anabolic steroid (AS) use between
      AS users and non-users provides potentially important clues to understanding AS
      use. Two groups of bodybuilders were used in this comparison: AS users (n = 20)
      and non-users (n = 27). Subjects completed a 40-item scale measuring their
      beliefs about the effects of steroids, both physical and psychological (Beliefs
      About Steroids Scale: BASS). MANOVA comparisons between AS users and non-users on
      the BASS items indicate that AS-using bodybuilders believe that AS enhance their
      physical strength, athletic ability, confidence, assertiveness, feelings of
      sexuality, and feelings of optimism.

PMID- 8861401
TI  - Prediction of attrition from day hospital treatment in lower socioeconomic
      cocaine-dependent men.
AB  - This study attempted to identify predictors of completion of a 27 h/week 4-week
      day hospital program for cocaine dependence. The research subjects were 95 lower
      socioeconomic, primarily African American male veterans. Of a wide range of
      predictor variables available at baseline, including sociodemographic and
      historical information, Addiction Severity Index data, psychiatric diagnoses, SCL
      90 measures, and measures of craving and familial alcoholism, only the cocaine
      urine toxicology result and self report of days of cocaine use in the past 30
      days (log transformed) were significant predictors. The urine toxicology result
      was the more powerful predictor with 73 percent with a negative urine completing
      treatment, as contrasted with 36 percent with a positive urine. Three additional
      measures obtained at the end of treatment week 1 further increased ability to
      predict treatment completion/attrition. Two of these measures were based on
      counsellor ratings and one was based on the patient's report of psychiatric
      treatment services received during the first treatment week. Thus, patients at
      high risk for dropout can be identified fairly early. Whether treatments can be
      adapted to retain such patients is an important question for the field.

PMID- 8861402
TI  - Stability of opioid craving over time as measured by visual analog scales.
AB  - Sixteen methadone maintenance patients reported their 24-h peak opioid craving on
      a visual analog scale and the time of day at which the peak craving occurred on
      weekdays over a 4-week period. Both intersubject and intrasubject craving scores
      were highly variable. Craving scores did not correlate highly with time since the
      previous dose, mean methadone dose, requests for changes in maintenance dose, or
      occurrence of positive urine-drug screens. These data suggest that 24-h craving
      recall (as measured by visual analog scales) varies over time and is not closely
      correlated with changes in methadone blood levels.

PMID- 8861403
TI  - Conditions sufficient for the production of oral cocaine or lidocaine self
      administration in preference to water.
AB  - Groups of rats were given a chronic history of drinking cocaine solutions of
      different concentrations in daily, 3-h schedule induced polydipsia sessions.
      Animals failed to develop a preference for cocaine solution to concurrently
      presented water. Schedule-induction conditions were maintained, and the animals
      were divided into separate groups, drinking either cocaine or lidocaine placed in
      a highly acceptable vehicle (glucose-saccharin solution). Animals preferred their
      respective drug solutions to concurrently presented water, and these preferences
      remained stable after the glucose-saccharin vehicle was gradually faded to water,
      leaving only cocaine or lidocaine, respectively, in the solution. Thus a stable
      preference for drug solution to water could be instituted in rats for either
      cocaine or lidocaine solution (putative reinforcing and nonreinforcing agents,
      respectively) given an appropriate associative history, with high intakes
      maintained by schedule-induction. Conditions sufficient for the initiation of an
      oral preference and high intake for a putatively reinforcing drug cannot be
      assumed to occur owing to the drug's reinforcing property in the absence of
      demonstrating the ineffectiveness of an appropriate negative control substance.

PMID- 8861405
TI  - A preliminary study of the relationship between long latency response and
      learning disorder.
AB  - The purpose of this preliminary investigation was to record long latency
      responses (LLR) from children with learning disabilities (LD) and to compare the
      findings with a normal group of children. LLRs were recorded from children with
      LD who had specific problems with language and were grouped as dyslexics. None of
      the children had Attention Deficit Disorder. Responses were recorded using
      clicks. N1 and P2 latency, N1-P2 amplitude and P2-P1 interpeak interval (IPI)
      were used as response parameters for analysis. IPI (P2-P1) was found to be
      significantly different between two test groups. None of the other measures
      differed significantly between the two groups.

PMID- 8861404
TI  - Non-fatal injuries and the use of psychoactive drugs among young adults in Spain.
AB  - We compared the prevalence of injuries requiring medical treatment in the general
      population, in cocaine users and in heroin users, and we studied the factors
      associated with the occurrence of injuries in these groups, using data from two
      interview surveys carried out in 1993 in Spain: the National Health Interview
      Survey, a national representative sample of the non-institutionalized general
      population, and a survey of a non-probability sample of heroin or cocaine users
      selected from the community. The subjects included in the study were persons 16
      40 years of age in urban areas: 4261 persons from the general population, 369
      cocaine users and 215 heroin users. The annual prevalence of injuries requiring
      medical treatment was 7.9 percent in the general population, 10.8 percent in
      cocaine users and 35.2 percent in heroin users. There was a statistically
      significant positive association of injury occurrence (1) among the general
      population: with male sex, alcohol use, use of tranquillizers/sleeping pills, and
      the use of antidepressants or stimulants; (2) in cocaine users: with the use of
      opiates other than heroin; and (3) in heroin users: with alcohol use, the use of
      tranquillizers/sleeping pills, and the injected route. The only statistically
      significant negative association was with the amount of cocaine consumed among
      heroin users. The results suggest that other psychoactive substances besides
      alcohol are positively associated with injury occurrence, and that cocaine use
      may contribute to a reduced risk of injuries associated with the use of
      depressants (alcohol, tranquillizers, heroin).

PMID- 8861406
TI  - Paired comparisons between the Classic 300 bone-anchored and conventional bone
      conduction hearing aids in terms of sound quality and speech intelligibility.
AB  - Fourteen experienced users of bone-anchored hearing aids conducted paired
      comparisons of sound quality and speech intelligibility for 6 and 4 different
      stimuli respectively in the Classic 300 and a bone-conduction hearing aid with a
      steel clip. Ten paired comparisons were made for each stimulus. The patient
      selected the best hearing aid and rated the chosen hearing aid on a scale of
      'somewhat better', 'better' and 'much better'. The Classic 300 obtained a
      positive assessment in terms of sound quality and speech intelligibility far more
      frequently. All the patients chose the Classic 300 as the best hearing aid when
      they assessed the sound quality of the classical music stimulus.

PMID- 8861407
TI  - Perceived sound quality of three bone-anchored hearing aid models.
AB  - Eighteen patients judged the sound quality of the new Classic 300 and the
      existing HC 100 or HC 200 on 4 five-stage sound quality scales. Two of the scales
      relate to the perceptual dimensions softness and clarity, one relates to
      interference or noise and one relates to the overall impression. The evaluations
      were made, based on a questionnaire, in the patients' own homes and comprised the
      listening situations: TV news, music, conversation with two to three people in a
      noisy environment and one optional choice. The patients also stated which hearing
      aid was best in each situation and made a confidence rating for their selection.
      The patients were accustomed to wearing the HC 100 or HC 200. In these
      comparisons of the different bone-anchored hearing aid models, the Classic 300
      received the best ratings overall. Seventeen patients changed their previously
      fitted hearing aid to a Classic 300 and satisfactory sound quality was
      undoubtedly one of the principal reasons. When it came to the confidence rating
      for their selections, some two-thirds of the patients stated that it was without
      hesitation or with little hesitation. Our overall conclusion is that the sound
      quality of bone-anchored hearing aids is satisfactory when it comes to clarity
      and overall impression. However, it may be expected that these patients with
      conductive losses get a better sound quality than other patients with
      sensorineural losses if the same type of aid is used.

PMID- 8861408
TI  - Early intervention for hearing impairment: differences in the timing of
      communicative and linguistic development.
AB  - This paper reports in-depth case study material which illuminates the impact of
      early aiding on the rate of acquisition of communicative and linguistic
      behaviours of a small group of severely and profoundly deaf infants (average
      better ear impairment of 101 dB) aided between 3 and 6 months of age. A
      comparison is made of each infant's development of gestural and vocal productions
      between the ages of 6 and 21 months. Data derive from video- and audio-recorded
      social interaction between deaf and hearing infants and their principal
      caregivers taken across three contexts. The effects of earlier identification,
      amplification and fluctuations in early auditory stimulation, on the deaf
      infants' acquisition of communicative, symbolic and linguistic skills are
      discussed.

PMID- 8861409
TI  - Isochronic mapping of the auditory brainstem response: normative results.
AB  - Isochronic mapping involves recording multi-channel evoked potentials from scalp
      electrodes and plotting contours of peak latencies. In this study, auditory
      brainstem responses were recorded from 20 electrode sites for left, right and
      binaural stimulation of each ear of 10 male and 10 female, normally hearing,
      young adults. Analysis of the data showed that the stimulus parameters of
      intensity, polarity and rate had no significant effect on the maps. On monaural
      stimulation, wave V was recorded first at the contralateral mastoid and
      ipsilaterally frontally and last at the ipsilateral mastoid some 350, mu s later.
      Binaural stimulation gave a symmetrical map, with wave V recorded first frontally
      and last at the occiput. In contrast, wave III was recorded first ipsilaterally
      and frontally and last at the contralateral mastoid. Wave II was recorded first
      at the rear of the contralateral mastoid and last forward of the ipsilateral
      mastoid. Comparisons between these results and human physiological studies are in
      agreement for waves V and III but do not support the concept of the VIIth nerve
      alone as the generator for wave II. These results suggest that this technique is
      a potentially useful diagnostic tool and it is intended to evaluate it by testing
      patients with a range of sensory, peripheral-neural and central-neural
      pathologies.

PMID- 8861410
TI  - A two-year follow-up examination of a behavioural treatment approach to hearing
      tactics.
AB  - Twenty elderly hearing impaired patients participated in a two-year follow-up
      study on the effects of behavioural treatment aimed at increasing coping with
      hearing impairment. Subjects who had received treatment were compared with
      untreated controls using the Hearing Coping Assessment (HCA) and the
      Communication Strategies Subscale of the Communication Profile for the Hearing
      Impaired (CPHI-CSS). The group treatment package included applied relaxation,
      video self-modelling, exposure, information, and the teaching of hearing tactics.
      Results showed some effects in favour of the treatment on the HCA at post
      treatment, but no differences at follow-up. The results on the CPHI-CSS using pre
      treatment HCA scores as covariate showed significant multivariate effects on the
      subscales measuring maladaptive behaviours, non-verbal strategies, and on the
      CPHI-CSS total score. No significant multivariate effect was found for the verbal
      strategies subscale. As no pre-treatment data were available, results on the CPHI
      CSS should be interpreted with caution. Overall, the results from this study give
      some support for the implementation of behavioural treatment in audiological
      rehabilitation.

PMID- 8861411
TI  - Recommended procedure: computer coding of audiometric thresholds.

PMID- 8861412
TI  - HIV/AIDS health worker stress and burnout: introduction and overview.

PMID- 8861413
TI  - Prediction of grief and HIV/AIDS-related burnout in volunteers.
AB  - Burnout in volunteer workers in the HIV/AIDS area results in the loss of
      dedicated personnel, consequently straining the HIV/AIDS care delivery system. By
      assessing the predictors of burnout and grief this study describes the role of
      grief in HIV/AIDS volunteer burnout. Voluntary and anonymous questionnaires were
      sent to members of the Foundation for Interfaith Research and Ministry (FIRM), a
      multi-religious organization formed to provide volunteer work in HIV/AIDS care
      facilities around Houston, Texas. In 174 valid responses, grief was measured
      against work characteristics, burnout, rewards, stressors, and the general health
      questionnaire (GHQ). No significant relationship was found between grief and
      burnout; however, burnout in volunteers may be different from that in health care
      professionals for the following reasons: (1) volunteers choose to work in the
      HIV/AIDS area; (2) they have control over the time they spend volunteering; (3)
      volunteers are internally motivated to work in the HIV/AIDS area; and (4) if the
      volunteers do not enjoy the work, they can terminate their involvement with
      minimal cost. The best univariate predictors of grief are time spent as a
      volunteer and volunteer hours per week, where those who spend the most hours
      volunteering experience less grief The Reward/Stress measures most significantly
      associated with grief include empathy/self-knowing reward, emotional support
      reward, and emotional overload stress. The strongest predictors of grief in the
      regression analysis, which account for 21% of the variance, were time as a
      volunteer, emotional support, emotional overload, GHQ-somatic symptoms, and GHQ
      social dysfunction. The data suggest that in order to reduce grief special
      attention should be paid te allowing volunteers freely to express problems with
      emotional overload and workload adjustments, and providing clear emotional
      support as a reward.

PMID- 8861414
TI  - The relationship between recognition, rewards and burnout in AIDS caring.
AB  - The positive psychological and sociological dimensions of AIDS care provision may
      produce important information to assist burnout prevention. While most studies on
      stress and burnout in AIDS health care have focused on the negative and difficult
      aspects of this work, few have considered the notion that the rewards of care
      giving may buffer against stress or counterbalance experiences that may otherwise
      lead to burnout. A study of HIV/AIDS volunteers examined the relationship between
      stressors, rewards and burnout, using the HIV Volunteer Inventory and the Maslach
      Burnout Inventory. Correlation data indicates that a lack of a sense of personal
      accomplishment is a contributor to frequency of burnout. Over a fifth of the
      variance of burnout frequency can be accounted for by both stress and reward
      factors. Qualitative interview data also support the importance of rewards.
      Rewards in the form of gratitude from clients and recognition and support from
      management positively influenced the organizational climate. This study points to
      the need to find ways to increase the recognition and rewards experienced by
      carers. The potential benefits include reduced attrition and burnout and enhanced
      quality of life in the work setting.

PMID- 8861416
TI  - Is there life after work? Experiences of HIV and oncology health staff.
AB  - A cross-sectional interview survey of 103 HIV/AIDS and 100 oncology staff in nine
      treatment sites in London aimed to identify ways in which work stress affected
      domestic and social lives of such staff. In all staff one-third of those without
      long-term emotional relationships stated they felt their work formed a barrier to
      their being involved in that way. Most subjects reported spending a considerable
      amount of time discussing work with partners, and work-related subjects caused
      conflict for just under half of the total sample. Thirty-nine percent reported
      their partners complained regularly about their commitment to work, and one
      quarter overall reported their relationship had suffered as a result of their
      work in HIV or oncology. Using tests of association comparing group responses to
      structured interview and standardized psychometric items, few differences were
      found overall between staff in HIV/AIDS and staff in oncology. HIV staff were
      more likely to be motivated to work through peer concern, and friends of HIV
      staff were more likely to be supportive of their working in such a field. On the
      other hand, families of oncology staff were more supportive of their work than
      were families of HIV staff HIV staff were more likely to have had a family member
      who had suffered from a chronic or life-threatening disease. HIV staff were less
      likely to avoid discussing their work socially. Suggestions for addressing the
      potentially corrosive impact of health care in these fields, based on these
      samples, are made.

PMID- 8861415
TI  - HIV counsellors' knowledge, attitudes and vulnerabilities to HIV in Lusaka,
      Zambia, 1994.
AB  - The objective of this study was to see how HIV affected counsellors in their
      personal and professional lives and how they coped. A total of 101 people who
      were currently working as HIV counsellors were interviewed. Of these, 70 had a
      relative who had died of HIV, but few had been able to discuss HIV with them.
      Seventy-two worried about their HIV status but only 24 had had a test. Fifty
      three counsellors did not want to know their status. Women counsellors worried
      because of the sexual behaviour of their partners and often felt unable to
      discuss HIV with them. Although nearly all were in favour of promoting condoms as
      protection against HIV transmission only 27 had ever used one. Many HIV
      counsellors found it difficult to discuss sexual behaviour with their clients.
      HIV counsellors in Zambia worry about HIV in their personal lives and need
      continuing confidential support to help them cope with their own worries as well
      as the anxieties created by the job itself They need more help and training in
      discussing issues around sexual behaviour with their clients. Women counsellors,
      in particular, need support in dealing with their personal sexual life.

PMID- 8861417
TI  - Psychological stress in nurses' relationships with HIV-infected patients: the
      risk of burnout syndrome.
AB  - To assess the role played by psychological stress and sociodemographic factors as
      predictors of burnout in nurses, we administered the AIDS Impact Scale (AIS) and
      the Maslach Burnout Inventory (MBI) to nurses in the AIDS field. The sample was
      composed of 410 nurses from 19 departments for the treatment of infectious
      diseases. In these subjects we observed a low level of burnout in the MBI, but a
      small proportion had a high level of burnout We did not find significant
      associations between sociodemographic variables and the MBI scales. We found
      significant correlations between the MBI and three AIS scales that specifically
      assessed the emotional involvement of nurses in their relationships with
      patients. The results suggest that an empathic involved relationship seems to be
      protective towards burnout rather than a frustrating involved relationship.
      Moreover nurses tolerate stress better if they receive supportive social rewards.
      We found that the impact of working with HIV-infected patients causes
      psychological stress (measured with the AIS), but it is a weak predictor of
      burnout (measured with the MBI). The results indicated the incompatibility
      between the relational/defensive model of the AIS and the environmental/work
      performance model of the MBI.

PMID- 8861418
TI  - Burnout, social support and AIDS volunteers.
AB  - Care providers working with people with HIV have shown high levels of burnout
      (Maslach, 1986) as staff were required to deal with a multi-faceted disease while
      creating new ways of working with clients. At the same time high burnout levels
      were also being seen among volunteers who were supplementing the work of paid
      staff. This paper looks at the impact that social support from agency staff and
      other volunteers had on the ability of volunteers working at The Gay Men's Health
      Crisis (GMHC) in New York City td deal with HIV volunteering, the rewards they
      experienced through volunteering and their experience of burnout.

PMID- 8861419
TI  - Burnout and related factors among HIV/AIDS health care workers.
AB  - A sample of 194 Italian health care-givers working in HIV/AIDS units was assessed
      to investigate whether there was a correlation between individual variables
      (socio-demographic and occupational characteristics, personality traits, anxiety,
      depression, attitudes and emotional reactions) and burnout and job satisfaction.
      For this proposal were used the Maslach Burnout Inventory (MBI), a socio
      demographic and occupational characteristics schedule. Sixteen Personality Factor
      Questionnaire, Ipat Anxiety Scale, Ipat Depression Scale and AIDS Impact
      Questionnaire. A principal component analysis on frequency subscales scores of
      MBI extracted two independent dimensions labelled 'burnout' and 'personal
      accomplishment'. The results suggested important correlations among 'burnout',
      'personal accomplishment', anxiety and depression. Age of care-givers was
      negatively correlated with 'burnout' and practical nurses were less personally
      accomplished. Anxiety, depression, emotional reactions, attitudes, ego strength,
      and the aptitude for interpersonal relationships and to team work were
      significant factors in outlining a profile of highly 'burned out' and 'personally
      accomplished' HIV/AIDS health care-givers. These results suggest the development
      of precise strategies of prevention, intervention and treatment of burnout
      considering not only the importance of occupational and institutional
      characteristics but also of individuals ones.

PMID- 8861420
TI  - AIDS-related beliefs, attitudes and intentions among Malawian students in three
      secondary schools.
AB  - This preliminary investigation into factors influencing the intention of Malawian
      secondary school students to engage in low-risk AIDS-related behaviours was based
      on the Theory of Reasoned Action (Ajzen & Fishbein, 1980). A total of 191 male
      and female subjects (mean age 19.32) from three secondary schools in Malawi
      filled in a questionnaire that sought to elicit their intention to use condoms
      and to stick to the one same sexual partner. The study lent support to the theory
      that intention can be predicted from attitudes and subjective norms, F(2,186) =
      31.93, p < 0.001 for condom use and F(2, 187) = 15.23, p < 0.001 for sticking to
      one sexual partner. The results showed that, for the subjects, the intention to
      comply with these two behavioural regimens was predominantly under attitudinal
      control though one sub-sample's intention was under normative influence. The
      study also provided quantitative data on the sexual behavioural patterns of the
      subjects and used these data to furnish explanations of the main findings.
      Behavioural change intervention strategies in the light of the findings are
      discussed.

PMID- 8861421
TI  - Research in psychopathology in patients with HIV/AIDS and psychiatric services in
      Spain.
AB  - In this article, we review the research carried out in Spain concerning
      psychiatric aspects of HIV/AIDS in general, and of suicide and suicidal ideation
      in particular. The paper presents available information concerning this
      psychopathology in patients with HIV infection, along with a review of the
      epidemic's dimensions and friends in Spain. Available studies are based on
      retrospective evaluation of patients referred for psychiatric evaluations. No
      longitudinal studies have been carried out, nor studies on the prevalence of
      psychiatric disorders in unreferred samples of HIV-infected patients. This
      neglected area of research is also a neglected area of care within Spain's mental
      health system.

PMID- 8861422
TI  - Reflections on the 9th International Conference on AIDS Education-- Interventions
      in Multi-cultural Societies, Israel 25 November-1 December, 1995.

PMID- 8861423
TI  - Heart transplant for the failing ischaemic ventricle.
AB  - Clinical application of heart transplantation goes beyond 28 years experience.
      Ischaemic heart diseases remain, with idiopathic cardiomyopathies, the main
      indications for cardiac transplant. A combination of haemodynamic, contractile
      and viability measurements may be useful to choose between transplant and
      coronary revascularization for the failing ischaemic ventricle. Advances in the
      detection of early rejection, improved organ preservation procedures, and the
      introduction of new immunosuppressive therapy protocols have produced dramatic
      results in heart transplantation. Late graft atherosclerosis remains a serious
      threat despite retransplantation and, in some cases, mechanical circulatory
      support.

PMID- 8861424
TI  - Lesion width as a discriminator of plaque characteristics.
AB  - This study evaluated the relative ability of two techniques to quantify carotid
      atheroma. Diameter stenosis and lesion width were used to predict clinical
      significance and morphologic characteristics of 54 carotid endarterectomy
      specimens. Diameter stenosis was a better predictor of symptoms than lesion width
      (P=0.03 versus P=0.085). Both parameters were predictive of complex atheroma
      (diameter stenosis P=0.000; lesion width P=0.03). However, use of lesion width
      allowed finer definition of categories permitting more precise subclassification
      of plaque. This resulted in a better correlation of symptoms to complexity when
      lesion width was used as the discriminating variable (lesion width P=0.04;
      diameter stenosis P=0.121). Lesion width is a valuable parameter for the
      classification of carotid atheroma, correlating with symptoms and plaque
      complexity. Lesion width should be evaluated in future studies of carotid
      atheroma. The discriminative ability of lesion width as detected by high
      resolution ultrasonography needs to be evaluated.

PMID- 8861425
TI  - Measurement of carotid bifurcation pressure gradients using the Bernoulli
      principle.
AB  - Current randomized prospective studies suggest that the degree of carotid
      stenosis is a critical element in deciding whether surgical or medical treatment
      is appropriate. Of potential interest is the actual pressure drop caused by the
      blockage, but no direct non-invasive means of quantifying the hemodynamic
      consequences of carotid artery stenoses currently exists. The present prospective
      study examined whether preoperative pulsed-Doppler duplex ultrasonographic
      velocity (v) measurements could be used to predict pressure gradients (delta P)
      caused by carotid artery stenoses, and whether such measurements could be used to
      predict angiographic percent diameter reduction. Preoperative Doppler velocity
      and intraoperative direct pressure measurements were obtained, and per cent
      diameter angiographic stenosis measured in 76 consecutive patients who underwent
      77 elective carotid endarterectomies. Using the Bernoulli principle (delta P =
      4v(2), pressure gradients across the stenoses were calculated. The predicted
      delta P, as well as absolute velocities and internal carotid artery/common
      carotid velocity ratios were compared with the actual delta P measured
      intraoperatively and with preoperative angiography and oculopneumoplethysmography
      (OPG) results. An end-diastolic velocity of > or = 1 m/s and an end-diastolic
      internal carotid artery/common carotid artery velocity ratio of > or = 10
      predicted a 50% diameter angiographic stenosis with 100% specificity. Although
      statistical significance was reached, preoperative pressure gradients derived
      from the Bernoulli equation could not predict actual individual intraoperative
      pressure gradients with enough accuracy to allow decision making on an individual
      basis. Velocity measurements were as specific and more sensitive than OPG
      results. Delta P as predicted by the Bernoulli equation is not sufficiently
      accurate at the carotid bifurcation to be useful for clinical decision making on
      an individual basis. However, end-diastolic velocities alone as well as internal
      carotid artery/ common carotid artery velocity ratios are highly specific in the
      prediction of clinically significant carotid stenoses. An end-diastolic velocity
      of > or = 1 m/s accurately identifies a 50% or greater diameter stenosis, and
      thus may in some cases be sufficient for operation.

PMID- 8861426
TI  - Management of arterial occlusive disease following radiation therapy.
AB  - Clinically significant arterial occlusive disease developed in 26 patients at
      between 5 months and 44 years (mean(s.d.) 10.7(12.0) years) following radiation
      therapy. Therapeutic radiation was associated with lesions of the carotid artery
      (nine patients), subclavian-axillary arteries (seven) and the abdominal aorta and
      its branches (10). Clinical presentations included transient ischemic attack,
      stroke, vertebrobasilar insufficiency, carotid bruit, upper- or lower-extremity
      ischemia and renovascular hypertension. Surgery for cerebrovascular insufficiency
      included carotid endarterectomy with vein patch, interposition grafting or
      subclavian-to-carotid bypass. Carotid or subclavian-to-axillary bypass was
      performed for upper-extremity ischemia. A combination of endarterectomy and
      Dacron or saphenous vein grafts was used for infrarenal reconstruction. Tunnels
      were placed orthotopically. Musculocutaneous flaps assisted in healing selected
      wounds. Ureteral catheters were useful adjuncts in abdominal vascular
      reconstructions. There were no operative deaths, strokes or amputations. One
      patient had recurrent transient ischemic attacks following subclavian-to-carotid
      bypass. The mean(s.d.) postoperative follow-up was 48.1(39.6) months. Patients
      presenting with end-organ ischemia following radiation therapy can be managed
      successfully with aggressive surgical revascularization using a broad spectrum of
      reconstructive techniques.

PMID- 8861427
TI  - Effects of pulsatile perfusion on human saphenous vein vasoreactivity: a
      preliminary report.
AB  - This study examined the effects of exposure to arterial blood pressure and flow
      on human saphenous vein catecholamine sensitivity. Unused portions of saphenous
      vein from eight patients undergoing peripheral bypass procedures were mounted
      parallel in a specially designed organ culture apparatus and perfused with tissue
      culture medium with 95% CO(2) at 37 degrees C. One segment was fixed between two
      cannulas while the medium was gently agitated (control) and the other was
      actively perfused via a pulsatile pump system at a rate of 60 beats/min, peak
      pressure of 100 mmHg and peak flow of 200 ml/min (pulsed; mean pressure 60 mmHg;
      mean flow 115 ml/min). After 48 h, vein segments were removed and tested for in
      vitro isometric contraction in response to KCI, norepinephrine and histamine, and
      relaxation in response to acetylcholine, calcium ionophore A23187, and sodium
      nitroprusside. There were no differences in mean(s.e.m.) maximal contraction in
      response to KCI (control 0.61(0.16) g versus pulsed 0.72(0.27)g; P = n.s.),
      norepinephrine (control 1.00(0.56) g versus pulsed 1.51(0.54) g; P= n.s.), or
      histamine (control 1.47(0.85) g versus pulsed 1.95(0.64) g; P= n.s.). However,
      pulsed veins exhibited increased sensitivity to both norepinephrine (control 
      logED50 6.20(0.23) versus pulsed mean(s.e.m.) 6.60(0.17); P< 0.05) and histamine
      (control -logED(50) 5.60(0.27) versus pulsed 6.24(0.20); P = 0.05). Pulsed veins
      exhibited slightly less acetylcholine-induced relaxation although the difference
      did not reach statistical significance (control mean(s.e.m.) relaxation at 1 x
      10(6)M 9.2(14.0)% versus pulsed -13.3(6.4)%; P = n.s.). There were no differences
      in relaxation in response to either A23187 (control 1 x 10-(4)M 178(19)% versus
      pulsed 191(68)% or sodium nitroprusside (control 225(15)% versus pulsed 254(17)%;
      P = n.s.). The data presented herein indicate that exposure of human saphenous
      vein to the hemodynamics of the arterial environment for 48 h results in
      catecholamine supersensitivity while contractile and relaxant function are not
      affected.

PMID- 8861428
TI  - A comparative study of endothelium-derived relaxing factor-mediated relaxation
      and smooth muscle cell function in arterial and venous vein bypass grafts.
AB  - The development of intimal hyperplasia in reversed vein grafts is associated with
      altered endothelial and vasomotor function. This study examines the effect of
      surgery on the morphology and vasomotor function of experimental arterial and
      venous vein bypass grafts. Twelve reversed vein grafts, 12 in situ vein grafts
      and 12 venovenous grafts were placed in 24 New Zealand White rabbits. All grafts
      remained patent and were harvested after 28 days. Isometric contraction to
      norepinephrine, histamine, bradykinin, serotonin and relaxation to acetylcholine
      and sodium nitroprusside following pre-contraction with prostaglandin F(2 alpha)
      were determined on the grafts and on contralateral jugular veins. Compared to the
      contralateral jugular veins, norepinephrine supersensitivity was induced in the
      reversed vein grafts, and venovenous vein grafts but not in the in situ vein
      grafts. Decrease in histamine sensitivity occurred in all grafted vessels.
      Bradykinin responses were significantly reduced in the in situ vein grafts and
      reversed vein grafts. Contractile responses to serotonin developed in the in situ
      vein grafts and reversed vein grafts only. Acetylcholine-induced endothelium
      derived relaxing factor-mediated relaxation of the contralateral jugular veins
      was preserved in both venovenous grafts and in situ vein grafts but was lost in
      reversed vein grafts. All tissues relaxed to sodium nitroprusside in dose
      dependent manner. The data suggest that norepinephrine supersensitivity in
      reversed vein grafts results from excision of the vessel. Attenuation of
      bradykinin responses and the enhanced contractile responses to serotonin appear
      predominantly to result from arterialization. Decreases in histamine sensitivity
      appear related both to excision and to arterialization. Neither the excision of
      the vein nor arterialization individually influences the alterations in
      endothelium-derived relaxing factor-mediated relaxation. However, a combination
      of excision and arterialization results in the altered endothelium-derived
      relaxing factor-mediated relaxation. This study suggests that the surgical
      preparation of the vein and the surgical procedure used have significantly
      different effects on endothelium-derived relaxing factor-mediated relaxation and
      smooth muscle contractility in vein grafts.

PMID- 8861429
TI  - Evaluation of distal run-off before femorodistal bypass.
AB  - The quality of distal run-off is one of the most important factors in determining
      outcome of femorodistal bypass. Accurate evaluation is important. Preoperative
      intra-arterial digital subtraction angiography and Doppler evaluation with pulse
      generated augmentation of 90 patients who underwent femorodistal reconstruction
      were compared with postoperative angiography. Underestimation of distal run-off
      of the calf vessels occurred in 33% of cases by preoperative intra-arterial
      digital subtraction angiography. A below-knee pulse-generated run-off score of 3
      or less was associated with a 12-month cumulative patency of 73% compared with
      85% with a below-knee pulse-generated run-off score of 4 or more (P=0.079, log
      rank test; P =0.060, Wilcoxon signed rank test). The 12-month cumulative patency
      for grafts with a complete, incomplete and occluded arch as defined by pulse
      generated run-off was 78, 90 and 38% respectively (P<0.0001 log rank and Wilcoxon
      signed rank tests). Preoperative evaluation of distal run-off before femorodistal
      bypass should not be based exclusively on intra-arterial digital subtraction
      angiography.

PMID- 8861430
TI  - Lateral approach to the popliteal and crural vessels for limb salvage.
AB  - Twenty-one patients underwent 23 bypasses for limb salvage via a lateral approach
      with subcutaneous graft tunneling. The reasons for utilizing a lateral approach
      were medial infection (10 bypasses), scarring from previous surgery (six),
      limited vein length available (three), prior local radiotherapy (two) and 'high
      risk' groin (two). The target artery was the anterior tibial in 16 cases, the
      peroneal in three, the above-knee popliteal in three and the dorsalis pedis in
      one. The median (range) follow-up was 22(<1-52) months. There were three early
      (within 30 days) and four late bypass occlusions, three of which occurred in
      previously revised bypasses and one in a non-compliant patient. The primary
      patency at 1 year was 61% and the secondary patency 86%. Only one amputation was
      required in the whole series. The lateral approach represents a simple solution
      to threatened limbs in otherwise difficult or complicated situations and may be
      the ideal approach for free vein grafts to the anterior tibial and distal
      peroneal arteries.

PMID- 8861431
TI  - Dacron stimulation of macrophage transforming growth factor-beta release.
AB  - This study evaluated the effect of Dacron on the release of macrophage
      transforming growth factor-beta (TGF-beta),an endothelial cell growth inhibitor.
      Rabbit peritoneal macrophages were grown in minimum essential medium (MEM) with
      10% fetal bovine serum (FBS) in the presence or absence of Dacron (0.5 mm x 3 mm
      particles). Media were collected three times each week for 7 weeks. For the TGF
      beta bioassay, mink lung epithelial cells (CCL64) were grown in MEM with 10% FBS.
      Test-conditioned media, 100 mu 1, were added (n = 4), and incubated 48 h. 3(H)
      Thymidine (3(H)-TdR) uptake was determined and compared with 3(H)-TdR uptake
      using known pure TGF-beta standards. Media samples were additionally pre
      incubated with a neutralizing anti-TGF-beta(1) antibody and the 3(H)-TdR uptake
      again quantitated. TGF-beta activity in the conditioned media of macrophages
      exposed to Dacron exceeded the control media groups in all weeks, reaching
      significance (P<0.05) in weeks 3, 4,5, 6 and 7. Pre-incubation of media samples
      with the anti-TGF-beta antibody inhibited this TGF-beta activity in all weeks
      with statistical significance in weeks 1, 2, 3, 5 and 7. The inhibitory effects
      of Dacron on endothelialization may be explained by the Dacron-induced release of
      TGF-beta from macrophages.

PMID- 8861432
TI  - Outcome of patients with symptomless carotid bruits: a prospective study.
AB  - Knowledge of the natural history of symptomless carotid artery disease is
      important in determining the best preventative treatment for symptom-free
      patients. To document the progression of carotid artery disease and the clinical
      course of a symptomless population, 336 patients with symptom-free carotid bruits
      were prospectively followed up initially with oculoplethysmography and
      subsequently with duplex scanning. During a mean follow-up of 4.87 years, eight
      patients (2.4%) suffered a stroke. Thirty-seven (11.0%) experienced transient
      ischaemic attacks (TIAS). The cumulative event rate (TIA plus stroke) was 13.4%
      (45/336). The annual event rates were 0.48% for stroke, 2.26% for TIA and 2.75%
      for all ischaemic events. In a subgroup of 69 high-grade carotid stenoses (80
      99%), 31 carotid endarterectomies were performed before the development of a TIA
      or stroke and 21 after the development of symptoms, while 17 lesions were
      followed-up non-operatively. The total event rate (TIA and stroke) was
      significantly greater in the non-operated compared with the operated arteries
      (51.0% versus 6.4% at 5 years, P=0.0034). However, most of the events which
      occurred in the non-operated group were TIAs (85.7%) rather than stroke. There
      was no difference In the death rate of the two groups (P>0.05). Review of serial
      duplex studies performed on 540 carotid arteries revealed that 382 arteries
      (70.7%) remained unchanged and 158 (29.3%) showed disease progression. Forty-four
      of the 540 arteries became symptomatic (TIA or stroke). In 29 of the 44, the
      event occurred without any change in diameter of the artery, while in 15 there
      was a change of at least one category greater stenosis. In 39 patients, the
      stenosis was at least 40% and in five the stenosis was under 40%. Nine events
      occurred in the patients with severe contralateral carotid stenoses (>60%). The
      incidence of TIA (32.2%), stroke (6.8%) and death (18.6%) was higher in patients
      with internal carotid artery stenoses in excess of 80% than in those with lesions
      between 0 and 79% stenosis (P<0.0001, P= 0.0367 and P=0.0236, respectively). In
      this study the incidence of cerebrovascular events was higher in patients with
      high-grade internal carotid artery disease, and the preservation of neurological
      status in patients with symptomless high-grade carotid artery stenosis was
      improved by carotid endarterectomy, although the overall mortality remained
      unchanged.

PMID- 8861433
TI  - Femoral artery aneurysms: long-term follow-up and results of surgical treatment.
AB  - Aneurysmal dilatation of the femoral artery is a rare condition of uncertain
      aetiology. Between January 1972 and December 1992, 31 atherosclerotic femoral
      aneurysms in 22 patients were seen. There were 21 men and 1 woman; mean(s.d.) age
      was 70.1(10.4) years. Thirteen (42%) femoral aneurysms (group 1) were isolated
      aneurysms, two being bilateral. Eighteen (58%) were associated with a non
      contiguous abdominal aortic aneurysm, four being unilateral and seven bilateral
      femoral aneurysms (group 2). The mean(s.d.) size of these aneurysms was 4.7(1.5)
      and 3.5(0.7)cm in groups 1 and 2 respectively (P< 0.01). Of the limbs in group
      1,12 were treated by an interposition bypass. A ruptured profunda femoris artery
      aneurysm was ligated in one limb as an emergency operation. All patients in group
      2 underwent an aortobifemoral graft. There was one operative death. Three early
      thromboses were observed; two autogenous saphenous vein interposition grafts and
      one limb of an aortobifemoral. One late thrombosis occurred in an expanded
      polytetrafluoroethylene graft in group 1. The five-year patency rate was 80% for
      group 1 and 88.9% for group 2 (P=n.s.). The overall 10-year limb salvage rate was
      100%. These findings suggest that isolated femoral aneurysms are larger and more
      frequently symptomatic than femoral aneurysms associated with an abdominal aortic
      aneurysm. The association between femoral aneurysm and abdominal aortic aneurysm
      was found to be higher in patients with bilateral femoral aneurysms compared with
      those with unilateral lesions (P< 0.05). In the treatment of isolated femoral
      aneurysms better early results were obtained with expanded
      polytetrafluoroethylene interposition grafts.

PMID- 8861434
TI  - Renal artery aneurysm: a report of 28 cases.
AB  - Renal artery aneurysms are being increasingly encountered due to the wider use of
      angiography. From 1972 to 1992, 28 patients with renal artery aneurysm were
      identified in the present study, including 18 women and 10 men, with a mean age
      of 58 years. The aneurysms were discovered incidentally in 39% of patients during
      evaluation for hypertension in 39%, and during investigation of abdominal pain in
      22%. Only 7% of patients had symptoms directly attributable to the aneurysm.
      Aneurysm size varied from 0.5cm to 8cm in diameter, with a mean of 2.1 cm. The
      main renal artery was involved in 52% of cases, and primary branches in 44%; the
      remainder were intraparenchymal. There was a slight right-sided predominance in
      this series. The etiology of the aneurysms included atherosclerosis (75%),
      fibromuscular disease (21%), and Ehlers-Danlos syndrome (4%). Surgical therapy
      was undertaken in 10 patients (36%). Procedures performed included aortorenal
      bypass in four patients, aneurysm excision and renal artery repair in three,
      partial nephrectomy in one, and total nephrectomy in two. Although the natural
      history of renal artery macroaneurysms is not known with certainty, potential
      complications include embolization and rupture. The authors' indications for
      surgery include: (a) symptomatic or enlarging aneurysms; (b) renal embolization;
      (c) aneurysms in pregnant females or those considering pregnancy; (d)
      renovascular hypertension; (e) aneurysms> 2.5cm. Most symptom-free aneurysm s<2.5
      cm in diameter can be safely treated expectantly.

PMID- 8861435
TI  - Eversion endarterectomy in surgery of the internal carotid artery.
AB  - A total of 361 eversion endarterectomies of the internal carotid artery have been
      carried out on 348 patients between January 1991 and December 1992. Of these
      patients, 126 were women and 222 were men; average age was 62.9 (range 42-84)
      years. Some 239 patients had hemispheric symptoms; 37 symptomless patients had a
      carotid endarterectomy before major vascular reconstruction, and 21 had the
      operation combined with heart surgery (19 aortocoronary bypasses, two valve
      replacements). In nine cases (2.5%) a 6-mm interposition graft was used because
      of unsuccessful eversion endarterectomy. Postoperative bleeding occurred in six
      patients (1.7%) and postoperative stroke in seven (1.9%); of these patients, four
      died and two still have mild neurological symptoms. Four reocclusions occurred
      during the first 6 months that the new method was used. Eversion endarterectomy
      of the internal carotid artery is a safe and useful technique and is comparable
      with standard endarterectomies. This technique may reduce the risk of restenosis.

PMID- 8861436
TI  - Femoropopliteal bypass revisited: an analysis of 138 cases.
AB  - Femoropopliteal bypass is utilized for infrainguinal arterial reconstruction in
      patients with claudication, rest pain, non-healing ulcers and gangrene. Reported
      patency and limb salvage rates have varied considerably and controversy exists
      concerning conduit choice. The purpose of this study was to review the authors'
      results with femoropopliteal bypass to determine factors which may influence
      outcome in a contemporary series of patients. Between 1986 and 1991, 138
      femoropopliteal bypasses were performed in 120 patients. Mean follow-up was 28
      (range 1-66) months. Autogenous vein was used in 59% and polytetrafluoroethylene
      (PTFE) in the remainder. Above-knee anastomoses were performed in 34% and below
      knee in 66%. The secondary patency for autogenous vein grafts (95% at 4 years)
      was significantly better than for PTFE grafts (69% at 4 years; P<0.01). Secondary
      patency for below-knee autogenous vein grafts also was better than that for below
      knee PTFE grafts (95% versus 50% at 4 years; P<0.02). Limb salavage rates were
      worse for below-knee PTFE grafts than all other groups (P<0.01). Eight of 15
      failed above-knee PTFE grafts were salvaged with below-knee autogenous vein
      grafts and did well. In the present series, autogenous vein femoropopliteal
      grafts demonstrated better overall patency and limb salvage. Below-knee PTFE
      bypasses should be reserved for limb salvage cases in patients without adequate
      autogenous conduits. Failed PTFE grafts can be salvaged by autogenous bypasses,
      yet an advantage to this approach was not seen.

PMID- 8861437
TI  - Prophylaxis of graft infection with rifampicin-bonded Gelseal graft: 2-year
      follow-up of a prospective clinical trial. Italian Investigators Group.
AB  - Between March 1991 and June 1992, 600 patients were treated with mono-, bifemoral
      or iliofemoral arterial graft revascularization for occlusions and/or aneurysms.
      The patients were divided into two groups: group A (n = 296) received a Gelseal
      Vascutek graft immersed for 15 min before implant in a solution containing 1
      mg/ml rifampicin; group B (n = 304) received an untreated Gelseal Vascutek graft.
      Both groups received perioperative antibiotic treatment with cephalosporins.
      Clinical follow-up was performed at 1, 6, 12 and 24 months after surgery to
      exclude signs of graft infection. Statistical analysis (X(2)) of pre-, intra- and
      postoperative risk factors showed both groups to be well matched. Among 600
      patients treated, the 2-year follow-up showed 12 cases of graft infection (2.0%):
      five in group A (1.7%) and seven in group B (2.3%) (P = n.s.). All cases of graft
      infection originated in the groin and Staphylococcus aureus was isolated in 50%
      of cases. Statistical analysis (Mann-Whitney U test) showed a significant
      prevalence of lymphatic complications and immediate redo surgery in patients with
      graft infection. Of the 12 cases with infection, one was lost to follow-up, three
      were treated with total graft removal, six with partial graft removal and two
      with conservative therapy: there were no deaths. In spite of the relatively
      limited series and follow-up, no statistically significant difference emerged
      from the clinical use of vascular grafts pretreated with antibiotics.

PMID- 8861438
TI  - 'In vivo' size of knitted Dacron prostheses (Gelseal) used in the thoracic aorta:
      a computed tomography study.
AB  - When replacing the thoracic aorta, gelatin-sealed triaxial knitted Dacron
      prostheses are used as they have zero porosity and are easy to handle. It is
      known that knitted prostheses (not triaxially constructed), when implanted in the
      abdominal aorta or in the peripheral vessels, show a dilatation of 10-20%. The
      initial in vivo expansion of this prosthesis in the thoracic aorta was assessed
      using computed tomography scanning in 18 patients. The graft sizes used were 18mm
      (n = 4). 20mm (n = 5). 22mm (n = 4), 26mm (n = 1), 28mm (n = 2) and 30mm (n = 2).
      All patients were kept normotensive postoperatively. Computed tomography scan
      measurement was performed within 4 weeks of operation. using standard computed
      tomography equipment and no contrast. Two radiologists checked and agreed upon
      the slice levels and measurements compared with the manufacturer's stated size
      referring to internal diameter of the crimped prosthesis. The mean(s.d.) 'in
      vivo' size was 16.2(6)% larger. This 'true size' should be taken as the reference
      measurement when considering further dilatation over the period of follow-up.

PMID- 8861439
TI  - Coronary artery bypass grafting without cardiopulmonary bypass for high-risk
      patients.
AB  - Between January 1991 and June 1993, coronary artery bypass grafting was performed
      without either cardiopulmonary bypass or cardiac arrest in 23 patients. Most
      patients had several surgical risk factors, including age > or = 70 years, poor
      left ventricular function, left main coronary artery stenosis, chronic renal
      failure, and aortic aneurysm. Distal anastomoses were made under temporary
      interruption of coronary flow. A total of 37 distal anastomoses to the left
      anterior descending coronary artery and/or right coronary artery (mean 1.6 per
      patient) were made, 24 of which were internal thoracic arteries. The coronary
      occlusion time ranged from 7-14 min (mean 9.8 min). Combined cardiac or vascular
      operations were carried out in six patients (abdominal aortic aneurysm repair,
      thoracic aortic aneurysm repair, carotid endarterectomy, and coronary
      endarterectomy). There was one hospital death. Postoperative angiography was
      performed in 22 patients and showed a patency rate of 89%. In summary, coronary
      artery bypass grafting without cardiopulmonary bypass may improve the
      postoperative outcome of high-risk patients.

PMID- 8861440
TI  - Free internal mammary artery graft in myocardial revascularization.
AB  - Between August 1986 and March 1993, 124 patients (102 men; mean age of 59 years)
      underwent myocardial revascularization with the use of at least one free internal
      mammary artery (FIMA). This group represents 4.5% of the 2725 coronary bypasses
      performed during the same period. Seventy-six patients (61%) had suffered from at
      least one previous myocardial infarction. Forty-five patients (36%) had unstable
      angina; three-vessel disease was found in 100 cases (80.5%) and a left
      ventricular ejection fraction lower than 0.4 in 22 (17.7%). There were 18 (14.5%)
      redo procedures and 90 (72.5%) bilateral internal mammary artery (IMA) grafts.
      The reasons for using a FIMA were: too short an internal mammary artery pedicle
      in 83 patients, IMA injury at harvesting in 30 patients and post-bypass ischaemia
      in areas grafted with pedicled IMA (PIMA) in 11 patients. Cardiopulmonary bypass,
      moderate hypothermia (30 degrees C) and crystalloid anterograde and retrograde
      cardioplegia were used in all cases. Sixty-seven FIMA grafts were anastomosed
      directly to the ascending aorta; 57 were sutured via a saphenous hood using a
      running suture of polypropylene 7/0 and three were anastomosed end-to-end to a
      PIMA graft. FIMA grafts were directed to the left anterior descending (34%), the
      circumflex (37%) and the right coronary artery (29%). In total, 179 anastomoses
      were constructed using 127 FIMA, 136 using PIMA and 158 using saphenous veins
      (3.8 anastomoses per patient). Hospital mortality and postoperative myocardial
      infarction rates were 5.6% (seven patients) and 3.2% (four patients),
      respectively. Cardiac-related mortality was 3.2% (four patients); three of these
      four patients had been operated on for evolving infarction and one underwent a
      redo procedure. Four of the 117 survivors died later on; in two, it was cardiac
      related and a result of global heart failure at 9 and 12 months. Of the 113
      remaining patients, 106 are symptom free after a mean follow-up of 28.2 (range 3
      84) months. Fifty-nine patients (50.4%) were restudied by angiography at a mean
      interval of 15 months. Patency rates of FIMA anastomosed either directly to the
      aorta or via a saphenous hood were 82.8 or 89.7%, respectively. Patency rates of
      FIMA directed to the left anterior descending, the circumflex and the right
      coronary artery were 85.7, 88 and 83.3%, respectively. Global FIMA patency was
      86.4%, while global PIMA patency was 100%. The FIMA mid-term patency rates
      compare unfavourably with those of PIMA: FIMA should therefore be restricted to
      the cases where PIMA or other pedicled arterial grafts are unavailable.

PMID- 8861441
TI  - Role of right gastroepiploic artery in myocardial revascularization with arterial
      grafts.
AB  - Between July 1990 and December 1992. 112 patients underwent myocardial
      revascularization with arterial grafts in the Department of Cardiac Surgery,
      University of Milan. Monovascular patients were excluded from the study. The
      right gastroepiploic artery was used in 44 patients (39.3%); mean age was 54.3
      years and reoperation rate 18.2%. Of the 44 patients, previous myocardial
      infarction had occurred in 25 (57%). Emergency operation was performed in one
      case (2%). Mean left ventricular shortening fraction was 36% and mean ejection
      fraction 58.6%. Coronary artery disease was bivascular in 10 patients (23%) and
      trivascular in 34 (77%). The arterial revascularization in patients with
      gastroepiploic artery was performed using a left internal thoracic artery graft
      in all 44 patients; the right internal thoracic artery was used in 18 (41%) and
      the inferior epigastric artery in two (4%). The sites of gastroepiploic artery
      grafting were 55% posterior descending, 16% right coronary artery, 11%
      posterolateral branch, 14% circumflex and in 4% posterior descending and
      posterolateral as sequential graft. No patient died; postoperative myocardial
      infarction rate was 4%. No complications related to gastroepiploic artery
      utilization were noted. Forty-three (98%) of the gastroepiploic artery group
      underwent graft reinvestigation: the arteries were correctly visualized in 41
      patients (95%) and were patent in 39 cases and stenotic in two. A mid-term
      postoperative stress test (mean 17.4 months) was performed in 91% of patients.
      Normal limits were found in 37 patients (92.5%) and an abnormal stress test
      result in three (7.5%). The contemporary follow-up showed no deaths or myocardial
      infarctions. Three patients (7%) had recurrent angina. The role of gastroepiploic
      artery in arterial revascularization has become fundamental, especially, it is
      believed, for the posterior or posterolateral left ventricular wall. The present
      data show the patients to be clinically and functionally well 1 year after
      operation.

PMID- 8861442
TI  - Changes in the proportion of types I and III collagen in the left ventricular
      wall of patients with post-irradiative pericarditis.
AB  - Pericardiectomy for post-irradiative constrictive pericarditis achieves poor
      results because of the extensive damage to the heart and pericardium caused by
      ionizing radiation. The extracellular structural protein, collagen, is
      responsible for the functional integrity of the myocardium and allows reversible
      interdigitation and the transmission of force between contracting myocytes.
      Collagen concentration and composition were examined in the cardiac tissue of
      three patients undergoing pericardiectomy and post-irradiative pericarditis.
      Normal heart tissue was taken at autopsy from patients without cardiac disease
      and acted as controls. Total collagen concentration (mean(s.e.m.)) was
      significantly increased in the ventricular tissue of patients with post
      irradiative pericarditis compared with that of the controls (119.8(16.6) versus
      50.4(5.2) mg/g dry weight, P<0.01). Although there was an increase in
      concentration of both type I and III collagen, a disproportional increase in type
      I was observed. The proportion of type III collagen was lower in patients with
      post-irradiative pericarditis than in the control group (33(2.6)% versus
      38.2(3.7)%, P<0.05). The results of the present study suggest that this marked
      alteration in collagen concentration and proportion may contribute to the
      impaired diastolic distensibility of the ventricles seen in this group of
      patients.

PMID- 8861443
TI  - Surgical treatment of Brucella endocarditis.
AB  - Between April 1987 and October 1992, six cases of Brucella endocarditis were
      operated on in the authors' hospital for valve replacement. They were five men
      and one woman with a mean(s.d.) age of 52(15) years (range 30-71 years). Three
      patients were in New York Heart Association (NYHA) class III and three in class
      IV. Two patients had previous history of rheumatic fever, one was a drug abuser,
      two had peripheral embolism and one constrictive pericarditis. Most were living
      in rural areas. Echocardiographic diagnoses were: severe aortic regurgitation in
      two patients, mixed disease in two and double valve involvement in two. Valve
      vegetations were demonstrated in two patients, valve calcification in two and
      annulus abscess in two others. Serological tests were positive in all patients.
      All patients had valve replacements and three were operated on as emergencies.
      Surgical findings were: valve vegetations in two patients, cusp perforation in
      two annulus abscess in two and prosthetic leak in two. Mean(s.d.) cardiopulmonary
      bypass time was 123(77) min with a mean ischaemic time of 79(43) min. All
      patients were given specific antibiotic treatment after surgery. There was no
      intraoperative mortality and the 5-year survival rate was 100%. Early
      reoperations were needed in three patients, two because of prosthetic leakage
      causing severe regurgitation and one for tamponade. The results suggests that
      Brucella endocarditis is rare, but still occurs in Mediterranean areas. Surgical
      replacement is needed in spite of antibiotic treatment and recurrences with
      prosthetic leaks are usual.

PMID- 8861444
TI  - Coronary artery surgery with induced temporary asystole and intermittent
      ventricular pacing: an experimental study.
AB  - Coronary artery bypass grafting performed without cardiopulmonary bypass presents
      a difficulty in performing coronary anastomoses on a beating heart. A non
      cardiopulmonary bypass technique in sheep by which individual sutures can be
      placed on a still heart is described. Epicardial pacing wires were placed and a
      curved needle passed between the aorta and pulmonary artery into the muscular
      interventricular septum and directed caudally and to the right. The tip of the
      needle now lay in the vicinity of the outflow of the bundle of His. No cardiac
      chamber or vital structures were traversed. Injection of lignocaine here resulted
      in immediate ventricular asystole. Ventricular pacing restored cardiac output.
      After establishing local control of the vessel coronary anastomosis was performed
      stopping ventricular pacing for the few seconds required to place a single suture
      and reinstating it between the passage of sutures. Reversion to sinus rhythm
      occurred spontaneously.

PMID- 8861445
TI  - Haemodynamic and echocardiographic characteristics of a stentless allograft
      mitral prosthesis: an in vitro study.
AB  - Poor long-term durability and impaired haemodynamic performance are known
      disadvantages of bioprosthetic heart valves when compared to valve replacement
      using aortic allografts. A new stentless allograft mitral implant was developed
      and tested in vitro in a left ventricular model and pulsatile flow system to
      evaluate hydrodynamic function. Mitral valves were excised from sheep hearts and
      the mitral annulus reinforced by a strip of ovine pericardium. A patch of
      expanded polytetrafluoroethylene (ePTFE) was placed above the tips of the
      remaining papillary muscles. For in vitro evaluation of a total of five valves
      were investigated in a pulse duplicator. Transvalvular pressure gradients (delta
      P) were measured over a flow range corresponding to a cardiac output of 5l/min,
      at a heart rate of 70 beats/min, with a systole accounting for approximately 35%
      of the cardiac cycle. The systolic ejection period and diastolic filling period
      in this model were 350 and 510 ms, respectively, and aortic pressure was 120/80
      mmHg. The effective orifice area was calculated from measurements of mean
      pressure drop and root mean square flow. Additionally, valve performance was
      evaluated by Doppler echocardiography. Results of in vitro studies of a 25 mm
      stentless allograft mitral implant, which is similar to the valves implanted in a
      chronic weaning sheep model, revealed a mean(s.d.) delta P of 2.0(1.6) mmHg
      (range 1.0-4.9 mmHg). The mean calculated effective orifice area was 3.38(0.52)
      cm(2) (range 2.5-3.8 cm(2)). Doppler echocardiography showed excellent
      performance of the mitral valve components and valve competence could be
      achieved. During the in vitro studies no failure caused by tissue rupture was
      detected. The results of the in vitro studies revealed data for delta P and
      effective orifice area superior to data obtained for standard 25 mm porcine
      bioprostheses.

PMID- 8861446
TI  - Cardiac surgery in the ninth decade of life.
AB  - This study considers 96 consecutive patients of more than 80 years of age who
      were referred for surgery for either valve replacement (n = 51) or myocardial
      revascularization (n = 45) between 1985 and 1992. The patients having valve
      surgery consisted chiefly or aortic valve replacements (AVR), with a total of 48
      (isolated in 44 and combined with another valve in 4 cases) being performed. Some
      70% were in New York Heart Association (NYHA) class III and IV and 21.5% had
      experienced syncope. Bioprosthetic valves were implanted in all patients with an
      average aortic cross-clamping time of 58 min. The 1-month mortality rate was 9.8%
      (5/51, one mitral valve replacement and four aortic valve replacements). Death
      was caused by perioperative haemorrhage (one), low cardiac output (one),
      cardiopulmonary failure (two) and multiorgan failure (one). The morbidity rate
      was 64%. The actuarial survival rate was 76, 67 and 46% at 1, 2 and 4 years,
      respectively. By 4 years 89% were in NYHA stages I and II, of the 45 patients
      having coronary artery bypass grafts, 85% were in NYHA class III or IV and 69%
      had progressive unstable angina. Some 29% had a stenosis of the left main
      coronary artery and 51% had multivessel disease. Each patient had a mean of two
      venous grafts. The in-hospital mortality rate was 11% (5/45) and 13% had a
      postoperative myocardial infarction. The actuarial survival rate was 80, 77, 60
      and 58% at 1,2,3 and 5 years, respectively, with 85% in NYHA class I or II. In
      spite of their chronological age, many octogenarian patients who are in good
      physical condition can be operated upon for coronary artery bypass grafts or
      aortic valve replacement with an acceptable operative risk, good surgical outcome
      with improved quality of life.

PMID- 8861447
TI  - Surgical treatment of ischaemic valve disease.
AB  - Mitral valve regurgitation secondary to ischaemic heart disease carries a
      significant mortality even after open-heart surgery. In this study, 21 patients
      with mitral regurgitation associated with ischaemic heart disease were evaluated
      with respect to valvular pathology. Pathological examination of the mitral valve
      revealed chorda elongation or rupture in seven patients (group 1), papillary
      muscle dysfunction in 10 (group 2), and papillary muscle rupture in four (group
      3). Significant preoperative characteristics in each group were subacute
      haemodynamic deterioration in group 1, chronic severe left ventricular failure in
      group 2, and a high incidence of acute renal failure associated with haemodynamic
      shock in group 3. Mitral valve plasty was performed in six patients and mitral
      valve replacement, using the St Jude Medical valve, in 15. Fourteen patients
      underwent mitral valve surgery combined with coronary artery bypass grafting.
      Mitral plasty was applied to the patients with low left ventricular function with
      mean(s.d.) fraction shortening of 19.2(6.2)% compared with 30.2(8.4)% in patients
      with mitral valve replacement. There were no operative deaths. Of four late
      deaths, two in group 1 resulted from infection and myocardial infarction,
      respectively and one in group 2 resulted from arrhythmia. One patient in group 3
      died from renal failure. It is suggested that incorporation of these therapeutic
      concepts may lead to satisfactory results in the surgical treatment of ischaemic
      mitral regurgitation.

PMID- 8861448
TI  - Transaortic approach has a role in the surgical treatment of ventricular septal
      defects.
AB  - A transaortic approach was used for surgical closure of ventricular septal
      defects (VSDs), sometimes as first choice and otherwise as an alternative
      approach. This paper presents the experience in a group of 124 patients who
      underwent VSD closure by a transaortic approach in an 18-year-period, between
      1974 and 1992. Patients were divided in three groups: (I) Isolated VSD, 89
      patients (mean age 7.6 years); (II) VSD associated with other malformations, 27
      patients (mean age 10.8 years); and (III) recurrent VSD, eight patients (mean age
      15.6 years). Two deaths occurred in the postoperative period (2/124), one after
      closure of VSD in a patient with severe pulmonary hypertension; another death was
      observed after transaortic closure of the VSD as part of the repair of a complex
      heart malformation. There were no instances of new right bundle branch block
      (RBBB) in the group operated on for isolated VSDs. Three cases of left bundle
      branch block (LBBB) (3.4%) occurred in the isolated VSD group. There were no
      cases of complete aortic valve (AV) block in the whole series and no instances of
      AV dysfunction. The transaortic approach is an alternative for the surgical
      treatment of ventricular septal defects. The ease of exposure and closure of
      defects suggest this technique to be a particularly attractive approach in the
      treatment of small to moderate-sized VSDs and also in recurrent VSDs.

PMID- 8861449
TI  - T-balloon carotid shunt: its use during surgical treatment of non-stenotic
      carotid artery lesions.
AB  - A simplified technique for employment of the T-balloon shunt during surgical
      correction of non-stenotic carotid lesions (coiling, kinking, elongation,
      aneurysm) is described. This technical device is safe and useful when an
      intraluminal shunt is recommended.

PMID- 8861450
TI  - Long-term extracorporeal membrane oxygenation in a newborn child after arterial
      switch operation.
AB  - A 7-day newborn girl with d-transposition of the great arteries (d-TGA) and
      complex coronary anatomy developed global myocardial dysfunction after arterial
      switch operation despite establishment of an effective coronary circulation.
      Extracorporeal membrane oxygenation was used for circulatory support for 163 h
      after the operation. On day 7 after surgery she was successfully weaned from
      extracorporeal membrane oxygenation and is currently symptom-free 10 months after
      the operation. This case illustrates the effectiveness of extracorporeal membrane
      oxygenation for circulatory support after the arterial switch operation. In such
      cases, establishing adequate coronary circulation during surgery mandatory to
      ensure a successful postoperative myocardial recovery.

PMID- 8861453
TI  - Long-term cryopreservation of autologous veins in rabbits.

PMID- 8861451
TI  - Blood cyst with a calcium stone originating from the right atrial septum.
AB  - Blood cysts of the heart in adults are extremely rare, and their origin is
      usually from the valvular apparatus. However, a case was encountered of a blood
      cyst originating from the right atrial septum of a 59-year-old woman. Furthermore
      the cyst contained calcium stone. The cyst with the stone was Successfully
      excised. Neither situation has been reported previously in the literature.

PMID- 8861455
TI  - The vitamin-E derivative U-83836-E in the low-dose streptozocin- treated mouse:
      effects on diabetes development.
AB  - Low-dose streptozocin-treated (LDS) mice were administered an inhibitor of lipid
      peroxidation, U-83836-E (a derivative of vitamin E), in order to observe its
      ability to alter the onset of diabetes. Ten or 20 mg/kg body wt. per day of U
      83836-E were given to mice for 7 days and they were killed after 21 days. Results
      revealed that there was a significant increase in glycaemia in treated groups up
      to day 14 after which no further increase was noticed. Superoxide dismutase (SOD)
      assay showed that: (1) the LDS treatment significantly reduces SOD activity when
      compared with untreated controls (P < 0.005); (2) U-83836-E increases SOD levels
      (when compared with untreated controls); and (3) U-83836-E counteracts LDS
      treatment, since SOD activity is significantly higher with respect to that found
      in LDS-controls (P < 0.05), and SOD levels were significantly higher with respect
      to that found in Group 2 animals (P < 0.05), but significantly lower with respect
      to those found in groups 3 and 4 (P < 0.005). Moreover, malondialdehyde (MDA),
      the end-product of lipoperoxidation, was found at much higher levels in LDS
      controls than in the other groups and the lowest values were found in U-83836-E
      controls and in normoglycaemic animals treated with both streptozocin and U-83836
      E. Morphological observations demonstrated that islet beta cells were of normal
      appearance in normoglycaemic animals of the treated groups. In conclusion, the in
      vivo inhibition of lipid peroxidation by this compound produces a limited but
      significant prevention of the islet beta cell destruction.

PMID- 8861454
TI  - Effects of cilostazol on development of experimental diabetic neuropathy:
      functional and structural studies, and Na+ -K+ -ATPase acidity in peripheral
      nerve in rats with streptozotocin-induced diabetes.
AB  - We studied the ability of cilostazol (CL), an antithrombotic and vasodilating
      agent, to prevent functional, structural and biochemical abnormalities including
      delayed motor nerve conduction velocity (MNCV), morphological changes in
      myelinated fibers, and decreased Na(+)-K(+) -ATPase activity in the peripheral
      nerves of rats with streptozotocin (STZ)-induced diabetes. Cilostazol treatment
      (30 mg/kg/day p.o.) for 10 weeks significantly prevented the delay in MNCV in the
      tail nerve, and morphometric analysis of the sural nerves revealed that this dose
      of cilostazol had a significant effect on reduction of average size of myelinated
      fibers. In untreated diabetic rats, cyclic AMP content and Na(+)-K(+)-ATPase
      activity of peripheral nerve were each significantly less than in normal control
      rats. Cilostazol (30 mg/kg/day) prevented reduction of Na(+)-K(+)-ATPase
      activity. Decrease in cyclic AMP content was completely prevented with both doses
      of cilostazol (30 and 10 mg/kg/day). These findings suggest that cilostazol may
      have beneficial effects in the treatment of diabetic neuropathy, possibly via
      improvement of nerve Na(+)-K(+) -ATPase activity and cyclic AMP content.
      Cilostazol may thus be a potent drug for the clinical treatment of diabetic
      neuropathy.

PMID- 8861456
TI  - Adrenoceptor antagonists, but not guanethidine, reduce glucopenia-induced
      glucagon secretion from perfused rat pancreas.
AB  - This study was designed to investigate (1) whether norepinephrine is released in
      response to glucopenia in vitro, thereby stimulating glucagon secretion and, (2)
      the modulating effects of norepinephrine on insulin and glucagon secretion, using
      isolated perfused rat pancreas preparations. Simultaneous addition of the
      adrenergic receptor antagonists yohimbine, prazosin and propranolol, each at a
      concentration of 10-(5) mol/l, significantly potentiated glucose-stimulated
      insulin secretion (6.23 +/- 0.76 vs. 2.11 +/- 0.72 (control) nmol/min, P < 0.01),
      and suppressed glucopenia-induced glucagon secretion (0.59 +/- 0.10 vs. 1.34 +
      0.18 (control) ng/min, P < 0.05). Also, 10-(5) mol/l yohimbine alone
      significantly potentiated glucose-stimulated insulin secretion (4.86 +/- 0.50
      nmol/min, P < 0.05). The norepinephrine release inhibitor, guanethidine,
      significantly inhibited tyramine-induced secretion of both norepinephrine (7.86
      +/- 0.77 vs. 49.7 +/- 2.3 nmol/min, P < 0.01) and glucagon (0.31 +/- 0.08 vs.
      1.21 +/- 0.15 ng/min, P < 0.01), but exerted no effects on glucopenia-induced
      secretion of either norepinephrine or glucagon. We conclude that these results
      further support the concept that the neurotransmitter norepinephrine is released
      in response to glucopenia in vitro, and modulates insulin and glucagon secretion.
      Our data do not, however, provide evidence indicating that glucopenia-induced
      glucagon secretion is mainly mediated by activation of sympathetic nerve
      terminals around the alpha-cells in the isolated perfused rat pancreas.

PMID- 8861457
TI  - The effects of oophorectomy and female sex steroids on glucose kinetics in the
      rat.
AB  - In order to clarify the roles played by female sex steroids on glucose
      metabolism, basal glucose kinetics were studied in control sham operated (C),
      oophorectomised (O), 17-beta-oestradiol treated oophorectomised (1.5
      micrograms/day) (E) and progesterone treated oophorectomised (1.5 mg/day) (P)
      female rats. Hormone (or vehicle only) delivery was via osmotic pumps which were
      inserted at the time of oophorectomy (or sham operation) 7 days prior to
      metabolic testing. In fasted anaesthetised rats, hepatic glucose production
      (HGP), plasma glucose metabolic clearance rate (MCR) and glucose uptake indices
      (GUI) of selected peripheral tissues were measured using radioactive tracer
      methodology. Following surgery, the O rats significantly gained and the E rats
      significantly lost weight compared to the C rats. Plasma insulin and glucose were
      not different between groups. HGP and MCR were increased by 24-29% (P < 0.005)
      and 19-28% (P < 0.001), respectively, in the O compared to the C, E and P rats.
      The GUI of brown adipose tissue was significantly reduced in the P compared to
      the C rats (3 +/- 1 vs 25 +/- 10 micromol/100 g/min). In conclusion, female sex
      steroid hormones significantly influence rat body weight, hepatic glucose
      metabolism and the metabolism of brown adipose tissue.

PMID- 8861458
TI  - Haemoglobin A(1c) measurement for diabetes among subjects with a previous history
      of impaired glucose tolerance.
AB  - Haemoglobin A(1c) (HbA(1c)) measurement for diagnosis of diabetes and impaired
      glucose tolerance (IGT) was assessed during a prospective study of subjects with
      IGT; 183 of the 207 IGT persons underwent the second oral glucose tolerance tests
      (OGTT) 2.1 years, on the average, after the first tests. HbA(1c) was administered
      to every participant before the second OGTTs. The results of HbA(1c) were
      compared with those of the second OGTTs. The sensitivity of HbA(1c) test was 71%
      for diabetes and 41% for IGT, when the specificity was 93% at a cutoff point of
      4.81%. The conclusion is that the HbA(1c) test is moderately sensitive for
      diabetes but insensitive for IGT, when it is specific. However, it may be useful
      for selecting and reducing the total number of subjects referred to 2-h OGTTs in
      a follow-up study of subjects with IGT, if the rate of progression to diabetes is
      not high.

PMID- 8861459
TI  - Absence of increased susceptibility of LDL to oxidation in type 1 diabetics.
AB  - Insulin-dependent diabetics have a greatly increased risk of developing premature
      coronary artery disease which is not entirely explained by known risk factors. A
      possible explanation may be enhanced oxidative modification of low density
      lipoprotein (LDL). The aim of this study was to determine firstly, whether or not
      LDL from moderately well controlled type 1 diabetics is more readily oxidisable
      than LDL from healthy non-diabetics and, secondly, to assess whether potential
      predictors of LDL oxidisability differ between type 1 diabetics and controls.
      Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men
      on the basis of age and body mass index and each pair attended the department on
      the same morning for blood sampling. LDL oxidisability was assessed using both
      copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference
      between type 1 diabetics and controls in the susceptibility of the LDL to either
      copper-dependent or non-transition metal-dependent oxidation. Furthermore, there
      was no difference between the groups for LDL vitamin E content, LDL fatty acid
      composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper
      reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given
      the absence of increased LDL oxidisability in these subjects, the recommendation
      of vitamin E supplementation in type 1 diabetics should be considered a secondary
      priority to achieving adequate glucose control.

PMID- 8861460
TI  - A randomized, blinded trial of uncooked cornstarch to diminish nocturnal
      hypoglycemia at diabetes camp.
AB  - OBJECTIVE: To determine if uncooked cornstarch, as part of the evening snack, can
      avert nocturnal hypoglycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS:
      Fifty-one campers and counselors at the American Diabetes Association Camp in San
      Bernardino, CA were randomly assigned to receive 5 g of uncooked cornstarch as
      part of the 21:00 evening snack vs. a standard snack of equivalent carbohydrate
      content. Each snack was given for five nights and the participants and medical
      personnel were blinded as to assignment. Midnight and 07:00 finger stick blood
      glucose levels were compared with values <60 mg/dl defined as hypoglycemia and
      values > 250 mg/dl defined as hyperglycemia. RESULTS: There were 218 midnight and
      222 07:00 values for comparison. There were six episodes of hypoglycemia at
      midnight and nine episodes of hypoglycemia at 07:00 for the cornstarch snack
      nights vs. 30 hypoglycemia episodes at midnight and 21 at 07:00 for the standard
      snack nights (P < 0.001 and <0.05, respectively). There was no difference in the
      number of hyperglycemic events at midnight or 07:00 for the cornstarch vs.
      standard snack nights. At midnight, 12% of campers had hypoglycemia after the
      cornstarch snack vs. 46% after the standard snack (P < 0.001), and at 07:00, 16%
      had hypoglycemia after cornstarch vs. 26% after the standard snack (P = 0.327).
      CONCLUSIONS: These data suggest that uncooked cornstarch, as part of the evening
      snack, can diminish the nighttime and morning hypoglycemia associated with type 1
      diabetes, without causing hyperglycemia.

PMID- 8861462
TI  - High mortality from unidentified CVD in IDDM: time to start screening?
AB  - Mortality in insulin-dependent diabetes is markedly increased compared to the
      general population. Although strong associations have been found between renal
      disease and the risk of cardiovascular disease (CVD) the interaction between
      these two factors is not well understood. This study, which addresses risk
      factors for mortality in IDDM with a particular focus on the renal-CVD link, is
      based on the prospective Epidemiology of Diabetes Complications study. Thirty
      seven (mean age 36 years, mean duration of IDDM 28 years at baseline) of the 658
      IDDM individuals (mean age 28 years, mean duration of IDDM 20 years at baseline)
      have died in the first 4 years of follow up. A nested case-control study was
      performed, matching on sex and duration of diabetes. Twenty-two (59%) of the
      deaths were attributed to coronary heart disease, with an additional 16%
      attributed to diabetic coma. Only nine (41%) of the 22 individuals who died from
      cardiovascular disease had clinical evidence of coronary heart disease when seen
      for their last biennial exam. However, 54% of those who died of CVD without prior
      evidence did have evidence of lower extremity arterial disease. A strong link
      with renal disease was confirmed, with 81% of those with a coronary artery
      disease death having renal disease. Multivariate analyses suggest that smoking
      history, triglycerides and total platelet count are independent predictors of
      mortality, while LDL cholesterol best predicted CVD mortality. These results
      suggest a need for more intensive screening for cardiovascular disease, and
      correction of cardiovascular risk factors, in order to reduce the increased rate
      of mortality in this population. Efforts to prevent or delay the onset of renal
      disease may also be of benefit.

PMID- 8861461
TI  - Association of vagal tone with serum insulin, glucose, and diabetes mellitus--The
      ARIC Study.
AB  - Reduced vagal activity assessed by heart rate variability (HRV) has been observed
      in studies of diabetics, but this association has not been reported at the
      population level. To investigate the association of HRV with diabetes mellitus,
      as well as fasting serum insulin, and glucose, we examined a stratified random
      sample of 1933 individuals (154 diabetics and 1779 non-diabetics), aged 45-65
      years from the Atherosclerosis Risk in Communities (ARIC) study cohort. Two
      minute, resting, supine beat-to-beat heart rate records were collected. Power
      spectral density estimation was used to derive HRV high frequency power (HF, 0.15
      0.35 Hz) as the conventional marker of vagal function. Age, race, and gender
      adjusted geometric means of HF were 0.78 and 1.27 (beat/min)(2) for diabetics and
      non-diabetics respectively (P for mean difference <0.01), reflecting a reduced
      vagal activity in diabetics. In individuals not diagnosed as diabetics, a graded,
      inverse association was observed between fasting serum insulin and HF (P for
      trend <0.01): the age, race, and gender-adjusted geometric mean values of HF in
      the lowest and highest quartiles of serum insulin were 1.34 and 1.14
      (beat/minute)(2), respectively. A similar association was observed between
      glucose and HF in a univariate model, but not in the adjusted model. This first
      population-based study on this subject confirmed that diabetics have
      significantly lower vagal activity than non-diabetics. In individuals not
      diagnosed as diabetics, serum insulin, and, to a lesser degree, serum glucose
      were inversely associated with vagal function, suggesting a role in the
      pathogenesis of diabetic neuropathy.

PMID- 8861463
TI  - Diabetes mellitus in Kearns-Sayre syndrome: a case with a 10-year follow-up.
AB  - An 11-year-old girl with Kearns-Sayre Syndrome developed diabetes mellitus with
      ketoacidosis at onset and immediate insulin-requirement. In a 10-year follow-up,
      while neuromuscular disease was progressively increasing, diabetes was well
      controlled by once-a-day insulin therapy. Insulin secretion appears low, but
      without impairment during the years. This case points out the diabetes' features
      in Kearns-Sayre syndrome.

PMID- 8861464
TI  - Onset of diabetes with high titer anti-GAD antibody after IFN therapy for chronic
      hepatitis.
AB  - A case of hyperglycemia induced by the injection of interferon-alpha was
      experienced in our hospital. This patient showed a sustained high titer of anti
      GAD antibody after the onset of diabetes, suggesting that the involvement of
      immunological disturbance by IFN induces the onset of the disease. However, the
      susceptibility and the response of the immune system differs from patient to
      patient, and only limited destruction of beta-cells in the islet of Langerhans
      and normalization of glucose tolerance by CSII was induced in this patient.

PMID- 8861465
TI  - IDF Member Associations' activities presented in the 15th IDF Congress
      Exhibition.
AB  - IDF Member Associations' activities were presented in the 15th IDF Congress
      Exhibition held at Port Island, Kobe, Japan from November 7 to November 11, 1994.
      The purpose of the exhibition was to inform members of the progress on patient
      education, guidance of diet and exercise treatment, the compliance situation on
      self-monitoring of blood glucose, self-injection of insulin, etc., in each
      association. A total of 31 associations including 17 from outside Japan and 14
      from Japan participated in this exhibition. An exhibition theme was not
      designated to foreign associations. However, in order to avoid a similar content
      of exhibitions from the Japanese associations, a specific theme was assigned to
      each association. From these exhibitions we can comprehend the present status of
      the activities of all the diabetic associations in the world. Especially, an
      enthusiasm for patient and co-medical staff education in each association was
      clearly recognized. The total number of visitors including the commercial
      exhibition during the Congress reached about 17000 people.

PMID- 8861466
TI  - Partial liquid ventilation in newborn patients with congenital diaphragmatic
      hernia.
AB  - The authors evaluated the safety and efficacy of liquid ventilation with
      perfluorocarbon in four newborns with congenital diaphragmatic hernia and severe
      respiratory failure, who were on extracorporeal life support (ECLS). After 2 to 5
      days on the ECLS, perflubron was administered into the trachea until the
      dependent zone of the lung was filled. The first dose was 6 +/- 1 mL/kg (range, 5
      to 8 mL/kg). Gas ventilation of the perflubron-filled lung was performed (partial
      liquid ventilation). The administration of perflubron was repeated daily for 5 to
      6 days, with total cumulative doses of 36 +/- 8 mL/kg (range, 26 to 44 mL/kg). A
      significant increase in PaO(2) (P = .027 by repeated-measures analysis of
      variance [ANOVA]), a trend toward an increase in arterial oxygen content (P =
      .052 by repeated-measures ANOVA), and a significant increase in specific static
      total pulmonary compliance (P = .007 by repeated-measures ANOVA) were observed
      after administration of the daily dose of perflubron. PaCO(2) data showed a
      decreasing trend (P = .08 by repeated measures ANOVA). The authors conclude that
      perflubron can be safely administered into the lungs of newborn patients with
      congenital diaphragmatic hernia and severe respiratory failure, and it may be
      associated with improvement in gas exchange and pulmonary compliance.

PMID- 8861467
TI  - 10 years of pediatric liver transplantation.
AB  - PURPOSE: Pediatric liver transplantation is an accepted therapy for end-stage
      liver disease, but little long-term data exist. METHODS: From October 1984 to
      October 1994, 202 patients underwent a total of 225 liver transplantations. There
      were 98 boys and 104 girls, the average age was 5.1 +/- 4.9 (range, 0.2 to 19.1)
      years. Thirty (16%) were under 1 year of age. The diseases that required
      transplantation included biliary atresia (BA) (45%), metabolic liver disease
      (MLD) (9.9%), acute hepatic failure (6.9%), and Alagille's syndrome (AS) (5.4%).
      Originally the immunosuppression was cyclosporine- and steroid-based; the later
      regimens also included azathioprine and antilymphocyte preparations. All reported
      survival rates were derived from life-table analysis. RESULTS: The patient
      survival rates at 1, 5, and 10 years were 76%, 70%, and 61%; the
      retransplantation rate was 11%. The respective graft survival rates were 71%,
      63%, and 59%. There were 60 deaths; 48 (81%) occurred in the first year. These
      first-year deaths were from sepsis (20; 42%), central nervous system problems (5;
      11%), intraoperative complications (4; 8%), lymphoproliferative disease (LPD) (2;
      4%), rejection (2; 4%), primary nonfunction (2; 4%), and miscellaneous other
      causes (7; 15%). There were 12 deaths after the first year, from LPD (3; 25%),
      sepsis (1; 8%), rejection (2; 18%), cancer (1; 9%), secondary hepatic failure (1;
      9%), cerebral vascular accident (1; 9%), or pre- or postoperative complications
      (3; 25%). Compared with the overall survival rate, patients with MLD had a better
      chance of survival (83%; P <.012) than did those with AS (45%; P < .001). The 5-
      and 10-year survival rates for patients with BA were 61% and 58%. Over the past 2
      years, the survival rate has increased (87% v 72%; P < .05) as early septic
      deaths have decreased (from 2.6 to 1.0 per year). CONCLUSION: Liver
      transplantation is effective treatment for end-stage liver disease. Decreasing
      the number of early septic deaths has improved the chance of survival, and better
      diagnosis and treatment of LPD would improve the late survival rate.

PMID- 8861469
TI  - The rectoanal relaxation reflex and continence in repaired anorectal
      malformations with and without an internal sphincter-saving procedure.
AB  - From 1985 to 1994, 27 patients with high- or intermediate type imperforate anus
      who underwent anorectoplasty were studied for postoperative function,
      particularly with respect to the rectoanal relaxation reflex and continence.
      Fourteen of the patients had a rectourogenital fistula and were treated with
      posterior sagittal anorectoplasty using the fistular end as the neoanus (internal
      sphincter-saving). Nine patients had a blind rectal pouch and received posterior
      sagittal anorectoplasty using the trimmed bowel end for reconstruction of the
      neoanus (incomplete internal sphincter-saving). The other four had Rehbein's
      mucosa-stripping endorectal pull-through combined with anterior sagittal
      anorectoplasty (none internal sphincter-saving). A positive rectoanal relaxation
      reflex was found in 8 of 14 (57.1%), 7 of 9 (77.8%), and 3 of 4 (75%),
      respectively. It appears that the internal sphincter-saving procedure is not
      essential for the development of the rectoanal relaxation reflex. Compensation or
      adaptation most likely contributes to the presence of the rectoanal relaxation
      reflex, and perhaps to postoperative continence.

PMID- 8861468
TI  - The anterior sagittal approach for high imperforate anus: a simplification of the
      Mollard approach.
AB  - High imperforate anus is a complex anomaly that requires a combination of careful
      preservation of native structures and precise anatomic reconstruction for optimal
      results. Previously the authors used an anterior perineal approach derived from
      the technique described by Mollard, with generally satisfactory results. The
      present report describes the authors' refinement of the technique to avoid skin
      perineal approach, via an anterior sagittal incision, usually is combined with a
      transverse suprapubic laparotomy. The technique includes division of the external
      sphincter and longitudinal muscle fibers anteriority, simple dilatation of the
      puborectalis, and division of the fistula close to the urethra, with preservation
      of the internal sphincter. The rectal pouch is brought down to the level of the
      puborectalis, without tapering, and the anoderm is brought up to the level of the
      rectal pouch to construct a shorter anal canal with a normal anorectal angle.
      This technique maximally preserves internal sphincter function, preserves
      specialized anoderm for the anal canal, and avoids extensive pelvic dissection
      and division of the levator sling. It also facilitates repair in the neonatal
      period, which may be optimal for long-term continence. The authors have used this
      technique in five patients, with good anatomic and short-term functional results.
      The authors believe that the technique provides optimal preservation of native
      tissues; only minimal destruction and dissection are required for reconstruction.

PMID- 8861471
TI  - Somatic function, mental health, and psychosocial adjustment of adolescents with
      anorectal anomalies.
AB  - Thirty-three adolescents (aged 12 to 20 years; median, 15) with a corrected low
      (n = 17) or high (n = 16) anorectal anomaly were assessed using anorectal
      physiological examination, semistructured interviews [Child Assessment Schedule
      [CAS]), and questionnaires (Child Behavior Checklist [CBCL], Youth Self-Report
      [YSR]). Seven patients, all of whom had low malformations, were totally
      continent. Twenty-three (70%) had persistent dysfunction with staining (n = 12)
      or intermittent/constant soiling (n = 11). Twenty-four (73%) had flatus
      incontinence. Fecal incontinence correlated negatively with anal canal resting
      pressure (r = - .58, P = <.001) and squeeze pressure (r = -.54, P < .01). Three
      adolescents had a permanent colostomy. Nineteen patients (58%) met the criteria
      for a psychiatric diagnosis, and impairment of psychosocial function was found in
      24 (73%). The degree of psychosocial impairment correlated significantly with
      fecal incontinence (F = -.37, P < .05) and flatus incontinence (r = -.49, P <
      .01). Continence of flatus correlated significantly with mental health symptom
      scores (YSR: r = .52, P < .01; CAS:r = .53, P < .01). The findings indicated
      that, in addition to soiling, staining as well as fear of flatus are associated
      with psychiatric and psychosocial dysfunction among patients with anorectal
      malformations. Optimal treatment of patients with low and high anorectal
      anomalies requires somatic and psychological care and follow-up into adulthood.

PMID- 8861470
TI  - Urologic problems in anorectal malformations. Part 2: functional urologic
      sequelae.
AB  - A consecutive series of 90 children with anorectal malformations was reviewed for
      urologic problems related to lower urinary tract dysfunction. Neurogenic bladder
      sphincter dysfunction was seen in 22 patients (24%), all but one of whom had
      sacral agenesis. Vesicoureteral reflux was present in 60% of the patients with
      dysfunction, and 32% had reflux nephropathy. Urinary incontinence was present in
      91% of the patients who had bladder-sphincter dysfunction. However, the
      management of bladder-sphincter dysfunction and urinary incontinence was not as
      straightforward as for patients with myelodysplasia because the parents were more
      reluctant to accept the therapeutic measures. It was particularly difficult to
      introduce clean intermittent catheterization (CIC), especially in older patients,
      because genital and urethral sensation often was undisturbed. Only if CIC had
      been started in the neonatal period or early infancy were there no problems with
      acceptance and parental compliance. The authors emphasize the importance of
      urodynamic testing of neonates and infants who have an anorectal malformation and
      associated sacral agenesis in identifying those who have neurogenic bladder
      sphincter dysfunction. Consequently, patients with lower urinary tract
      dysfunction should receive prompt treatment, including CIC if necessary, to
      prevent or reduce secondary urologic morbidity, especially loss of renal
      function.

PMID- 8861472
TI  - Hepatitis C infection in children who received extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: To determine the prevalence of antibody to hepatitis C virus (HCV) in
      a cohort of neonates who received extracorporeal membrane oxygenation (ECMO)
      therapy, and to determine risk factors associated with seropositivity. DESIGN:
      Eighty-three patients who had been treated with ECMO as neonates (from August
      1986 through January 1992) at Children's Hospital, Boston, were tested for
      antibodies to HCV. The medical records were reviewed, and information regarding
      neonatal history was obtained. Anti-HCV seronegative and seropositive children
      were compared using univariate and multivariate analyses. RESULTS: Seven patients
      (8%) were anti-HCV seropositive of the seven seropositive children, four (57%)
      currently have ALT values of more than 1.5 times the upper limit of normal; only
      five of the 52 (9.6%) seronegative patients have values this high (P < .001).
      Patients in the seropositive group had received blood screened by "surrogate
      markers" (6 of 50) or by ELISA-1 anti-HCV testing (1 of 33). Significant
      differences between the seropositive and seronegative patients were found with
      respect to the aminotransferase and bilirubin levels during the initial ECMO
      hospitalization. The last ALT value before discharge was the only significant
      predictor of HCV infection in the multivariate model. CONCLUSION: Neonates
      treated with ECMO are at risk for the development of HCV infection. Neonates who
      received blood products from donors screened by surrogate markers or ELISA-1 anti
      HCV testing should be considered at risk. Neonates who had an abnormal ALT value
      at the time of discharge are most likely to be anti-HCV seropositive.

PMID- 8861473
TI  - Can ultrasonography replace computed tomography in the initial assessment of
      children with blunt abdominal trauma?
AB  - The evaluation of injured children with suspected blunt abdominal trauma (BAT) is
      clinically challenging. Computed tomography (CT) requires that patients be
      sedated, stable, and transportable, and even so, it is considered the diagnostic
      modality of choice for children with BAT. The authors questioned whether
      abdominal ultrasonography (US) performed during the initial assessment of the
      injured child is accurate enough to replace CT in the detection of intraabdominal
      injury. One hundred twenty-four children with BAT aged 2 to 14 years; (average,
      8.3) were admitted to the authors' institution during 1992 and 1993. Some had
      associated injuries (head, 60; chest, 25; extremities, 15; pelvis, 5). The
      indications for US were pelvic, abdominal, or lower chest trauma, tenderness, or
      guarding; altered consciousness; microhematuria; and/or low hemoglobin/hematocrit
      values. Three patients underwent abdominal CT at the time of admission. For 121
      children, an emergency US examination was performed using a 3.5-MHz transducer
      and a portable machine. The examination evaluated the kidneys, liver, and spleen
      for parenchymal injuries, and the subhepatic, subphrenic, and paracolic spaces
      and the pelvis for evidence of free peritoneal fluid. The presence of fluid
      and/or parenchymal injury was interpreted as a positive US result. Twenty-eight
      patients had positive US findings. Ten of these had a subsequent positive CT
      result, eight had a normal CT result, and 10 had a negative second US result.
      Eleven patients (with a total of 17 visceral injuries) were treated
      conservatively. One patient underwent emergency surgery for liver and caval
      injuries. Four patients required blood transfusions. Ninety-three of the 121(78%)
      had a negative US result. For one of these patients, a subsequent CT scan showed
      a minor subcapsular splenic hematoma, which resolved spontaneously. The authors
      conclude that US is sensitive in detecting free peritoneal fluid or visceral
      injuries and is an effective screening modality. It has replaced abdominal CT in
      76% of our patients with suspected BAT. In view of the reliability, simplicity,
      low cost, and bedside availability of US, the authors suggest that this modality
      be used in the initial assessment and diagnosis of children with suspected
      intraabdominal injury from blunt trauma.

PMID- 8861474
TI  - Cranial attachment of the gubernaculum associated with undescended testes.
AB  - Elongated epididymis is an abnormality encountered most frequently in patients
      who have an undescended testis (or testes). To clarify the implication of this
      anomaly in testicular descent, the anatomic configuration of paratesticular
      structures, especially the site of cranial attachment of the gubernaculum in
      relation to the configuration of the vas deferens, was evaluated in 54
      undescended testes of 44 patients. Undescended testes were associated with an
      elongated epididymis in 42.5% of cases. Of these, the cranial gubernaculum was
      attached solely to the vas deferens in 73.9%. In this group, the cranial
      gubernaculum was attached to the most descended part of the loop of the vas
      deferens. No patient with a nonelongated epididymis had a gubernaculum attached
      solely to the vas deferens. These results suggest that the abnormal attachment of
      the cranial gubernaculum in the embryological stage might affect the mode of
      descent of adjacent paratesticular structures.

PMID- 8861475
TI  - The incidence of positive contralateral inguinal exploration among preschool
      children--a retrospective and prospective study.
AB  - Retrospective and prospective studies were undertaken to evaluate the true
      incidence of bilateral inguinal involvement in preschool children in an
      established general pediatric population. Unbiased, anatomically based criteria
      were established for a "positive" exploration. It was found that bilateral
      inguinal involvement was highest during the first year of life (68%) and
      decreased through the advancing years, to just above 50% at 6 years of age.
      Because a widely patent processus vaginalis may be a precursor of indirect
      inguinal hernia, contralateral exploration may carry lifelong benefits in those
      who have the processus vaginalis ligated. Based on the authors' observations,
      contralateral exploration can be offered to all preschool children, and in
      selected cases (difficult preoperative preparation, anesthetic high risk, strong
      family history, etc), even beyond this age. Contralateral exploration is a safe,
      effective, and cost-wise practice when performed in an appropriate setting.

PMID- 8861476
TI  - Nitrergic innervation of the human gut during early fetal development.
AB  - Classically, development of the human enteric nervous system has been
      characterized by the early appearance (between 9 and 12 weeks' gestation) of
      adrenergic and cholinergic nerves. The development of peptidergic innervation
      occurs much later. Recent studies have indicated that nitric oxide is involved in
      the nonadrenergic noncholinergic innervation of the gut, mediating its
      relaxation. The authors have investigated the ontogeny of nitrergic (nitric oxide
      synthase-containing) neurons of the developing gut. Bowel segments from the
      esophagus, pylorus, and ileocecal and rectosigmoid regions of 14 fetuses
      (gestational age range, 12 to 23 weeks) were studied with nicotinamide adenosine
      dinucleotide phosphate (NADPH) diaphorase histochemistry. By 12 weeks' gestation,
      nitrergic neurons had appeared in the myenteric ganglia, at all levels of the
      gut, and had begun plexus formation. Nitrergic innervation in the submucous
      plexus becomes evident after 14 weeks. As gestational age increases, nitrergic
      innervation becomes richer and more organized. Increasing numbers of nitrergic
      nerve fibers are seen in the circular muscle; some of these fibers project from
      the myenteric plexus. By 23 weeks' gestation, nitrergic innervation has matured
      to the pattern observed in the postnatal gut. Thus, the onset and pace of
      development of nitrergic innervation are similar to adrenergic and cholinergic
      innervation and occur before peptidergic innervation. This study provides
      morphological evidence of the ontogenetic significance of nitrergic innervation
      in the human gut and supports previous suggestions that nitric oxide has a
      pathophysiological role in developmental gut motility disorders.

PMID- 8861477
TI  - Acute hypoxia does not increase bacterial translocation in newborn rabbits.
AB  - PURPOSE: We have previously demonstrated that spontaneous bacterial translocation
      (BT) occurs in newborn rabbits and correlates strongly with small bowel
      colonization (BC). Birth stress, specifically hypoxia, is believed to increase
      this pathologic process and thus lead to sepsis. This study investigated the
      relationship between BT and acute hypoxia in newborn rabbits. METHODS: Four
      hundred seventeen rabbit pups (aged 0, 2 to 4, 6, and 28 days) were divided into
      four groups according to the type of hypoxic stress: 9% O(2) for 1 hour, 9% O(2)
      + 12% CO(2) for 1 or 4 hours, and 21% O(2) (control animals). The animals were
      killed 1.5 or 20 hours after the stress. Sterile specimens of mesenteric lymph
      nodes (MIN), spleen, liver, small bowel, and large bowel were incubated
      aerobically at 37 degrees C for 24 hours in thioglycolate broth, and subsequently
      plated on both MacConkey and Colistin Naladixic Acid media. After 24 hours, the
      growth on both plates was recorded. X(2) analysis was used, and P values of less
      than .05 were considered significant. RESULTS: BC of the small bowel and BT to
      the MLN were low in the first 4 days of life in the hypoxic groups (range, 0% to
      21% BC, 0% to 6% BT) and the control group (range, 4% to 30% BC, 3% to 12% BT).
      After an increase in BC at 6 days of age, the rate of BT increased to 25% to 29%
      in control animals. The rate of BT in the hypoxic groups (25%) did not differ
      significantly from that of the controls (P > .05). Additionally, killing at 20
      hours (v 1.5 hours) was not associated with an increase in the incidence of BT.
      None of the stress groups had a significant increase in BT compared with the
      controls. Importantly, although 4 hours of 9% O(2) + 12% CO(2) resulted in a 30%
      mortality rate, the incidence of BT was no higher than that of the control
      animals (13% v 29%; P > .05). CONCLUSION: Severe hypoxic stress in newborn
      rabbits does not increase the incidence of BT. Because the incidence of BT
      correlates with that of BC, and because BC is the same in the control and hypoxic
      animals, the sepsis observed in hypoxic newborns probably is not related to an
      increased incidence of BT.

PMID- 8861478
TI  - Temporary impairment of lung function in infants with anterior abdominal wall
      defects who have undergone surgery.
AB  - Compliance of the respiratory system (CRS) was measured before and after surgical
      intervention in 14 infants who had anterior abdominal wall defects (AWD) (7
      exomphalos, 7 gastroschisis). The median gestational age was 37 weeks (range, 34
      to 40) and median birth weight was 2.38 kg (range, 1.94 to 3.45). The infants had
      stiff lungs before surgery (median CRS, 0.58 mL/cm H2(O)/kg). During the first
      and second postoperative days, the median CRS decreased to 0.33 mL/cm H2(O)/kg (P
      < .05). In seven cases, measurements also were obtained on the third and fourth
      postoperative days, which showed an increase in the median CRS (day 3, 0.47 mL/cm
      H2(O)/kg; P < .05). These findings show that in infants with AWD, primary
      surgical closure is associated with deterioration of lung function, but this
      effect is temporary.

PMID- 8861479
TI  - Penetrating chest injuries in children: a review of 94 cases.
AB  - Ninety-four children with penetrating chest injuries were treated at Dicle
      University School of Medicine during a 6-year period. The mean age was 11.51 +/-
      3.31 years, and the male:female ratio was 5.25:1. Forty-five had stab wounds, 27
      had high-velocity gunshot wounds, 13 had low-velocity gunshot wounds, seven had a
      bomb (shrapnel) injury, one had a shotgun wound, and one had a horse bite. Sixty
      patients had isolated thoracic injuries, and 34 had associated injuries. The most
      common thoracic injury was hemothorax (28), followed by hemopneumothorax (25).
      Tube thoracostomy alone was sufficient in 79.8% of the patients (75 of 94).
      Thoracotomy was performed in 4.25% (4 of 94). In two of the five observed
      patients, delayed hemothorax developed. The mean duration of hospitalization was
      5.13 +/- 1.93 days. The mean Injury Severity Score was 14.71 +/- 8.62.
      Prophylactic antibiotics were used in all patients. The morbidity rate was 8.51%
      (8 of 94). Only one death occurred after cervical tracheal repair. The study
      suggests that the majority of penetrating chest injuries in children can be
      treated successfully by tube thoracostomy alone or in conjunction with expectant
      observation.

PMID- 8861480
TI  - Abdominal cystic lymphangioma in children: benign lesions that can have a
      proliferative course.
AB  - Twenty-one pediatric cases of abdominal cystic lymphangioma (CL) treated in the
      past 20 years are reviewed. To date, this is the largest reported series. CL is a
      rare congenital malformation that presents either with chronic abdominal
      distension (and is detected by palpation of a cystic mass) or acutely with bowel
      obstruction or signs of peritonitis. It is more common among boys and most often
      occurs in children under 5 years of age. Abdominal ultrasonography is the
      procedure of choice for establishing the diagnosis. Acute cases with intracystic
      hemorrhage are more difficult to diagnose. Computed tomography and celioscopy may
      be useful. With these techniques, a correct diagnosis should be achieved in
      nearly every case. Enucleation (when feasible) or segmental intestinal resection
      (when the cyst is intimate to the bowel) is effective treatment. In a few cases
      the malformation is diffuse, and extensive bowel resection is necessary, with the
      risk of short bowel syndrome.

PMID- 8861481
TI  - Treatment of corrosive esophageal strictures by long-term stenting.
AB  - From 1975 through 1992, 932 patients with caustic esophageal burns were admitted
      to the author's institution. Deep circumferential burns were diagnosed
      esophagoscopically in 241 children within the first 48 hours postburn. Initial
      treatment consisted of periodic anterograde and/or retrograde dilations of the
      injured and scarring esophagus (n = 172). In 1989, a long-term stenting technique
      was introduced, and a total of 69 patients have been treated in this manner. The
      healing rates of patients treated with traditional therapy were compared with
      those of patients who had stenting, and a significant difference was noted (33% v
      68%; P <.01). Failure among the stented group was attributable to poor patient
      compliance and to gastroesophageal reflux resulting from shortening of the
      esophagus during scar formation.

PMID- 8861482
TI  - Ileal nutritional function after one-stage orthotopic ileum transplantation in
      the growing pig: reversal of lethal short bowel syndrome.
AB  - Intestinal isolation is associated with hypoplasia of defunctioned mucosa and
      reduction in the segmental absorption, whereas the presence of luminal nutrition
      is essential for the expression of the ileal adaptive response after proximal
      small bowel resection. On the other hand, intensive postoperative graft
      monitoring is obligatory because of the disastrous consequences of small bowel
      graft rejection. Thus, the authors sought to develop an experimental ileum
      transplantation model that provided immediate graft placement in bowel
      continuity, together with readily available graft monitoring connection through a
      proximal Roux-en-Y enterostomy. Four groups of pigs were prepared: RESTX (n = 9),
      proximal 50% small bowel resection with simultaneous orthotopic ileum
      autotransplantation; RES (n = 7), proximal 50% small bowel resection; NONRES (n =
      6), transection; and SB (n = 5), short bowel. Early (1 to 4 weeks) and long-term
      (5 to 12 weeks) studies of animal growth, nutritional status, disaccharide
      absorption, water and electrolyte balances, and liver function were performed
      after ileum autotransplantation (IAT) in relation to small intestine of variable
      length with undivided mesentery (intact neural and lymphatic connections). The
      perioperative transplantation mortality rate remained at about 10%. Reasons not
      related to the transplantation procedure accounted for the late complication rate
      of 38%. In the ileum autotransplantation (RESTX) group, weight gain was recovered
      2 to 3 weeks after transplantation, and the mean weight reached the preoperative
      level at 5 weeks. The SB pigs underwent progressive weight loss. The transection
      (NONRES) and proximal resection (RES) animals gained weight at similar rates. IAT
      had no effect on the plasma protein concentrations. Proximal resection, with or
      without IAT, was associated with depressed plasma cholesterol contents in the
      early period. Plasma cholesterol levels amended long-term, after both IAT and
      proximal resection. IAT resulted in deficient intraluminal processing of maltose,
      whereas isolated proximal resection tended to enhance disaccharide absorption
      early after the surgery. The short bowel pigs were not able to preserve
      sufficient nutritional status, and demonstrated a marked decline in the
      hemoglobin, protein, and cholesterol levels. No biochemical signs suggestive of
      potential liver damage caused by portocaval graft vascularization were
      recognized. These findings suggest that one-stage ileum autotransplantation
      provides sufficent absoprtive capacity to reverse otherwise lethal short bowel
      syndrome in the growing pig. However, transplantation disturbs the in vivo
      absorptive function of the nonrejecting ileum. Long-term impairment in
      disaccharide absorption may be partially related to an altered intestinal
      adaptive response secondary to proximal resection when combined with simultaneous
      transplantation. The authors developed this ileal small bowel transplantation
      model using rapidly growing pigs, wherein body weight gain represents an
      objective parameter of intestinal absorptive function. Only this type of animal
      model can yield clinically relevant data in the evaluation of a transplant's
      ability to provide sufficient nutritional function in a growing recipient.

PMID- 8861483
TI  - Perinatal intussusception in premature infants.
AB  - Intussusception is common in infants aged 5 to 18 months, but there have been
      only 12 reports of its occurrence among premature infants. Nine of these
      previously reported cases with adequate data and one new case are reviewed. Many
      of the infants were believed to have necrotizing enterocolitis, leading to an
      average 12-day interval between the onset of signs and the operation. Bilious
      emesis or nasogastric contents, bloody stool, and intestinal dilation without
      pneumatosis intestinalis were common. A contrast enema showed the intussusception
      in only 1 of 7 cases. Most cases were diagnosed in the operating room and
      underwent successful primary anastomosis, with no recurrences. A pathological
      lead point was identified in 2 of the 10 cases. The overall mortality rate was
      23%; the one death since 1970 was secondary to attempted hydrostatic reduction.
      These cases may represent what, in the absence of premature delivery, would have
      been the intrauterine development of intussusception likely leading to small
      bowel atresia.

PMID- 8861484
TI  - Spondylodiscitis and mediastinitis after esophageal perforation owing to a
      swallowed radiolucent foreign body.
AB  - A 6-year-old boy with aphagia presented with a radiolucent foreign body,
      esophageal perforation, mediastinitis, and a C6-C7 spondylodiscitis. A rigid
      plastic gear wheel was removed via thoracotomy, and the mediastinal abscess was
      drained through the esophagomediastinal fistula. Treatment included antibiotics
      as well as nonsurgical orthopedic management of the spondylodiscitis. The
      recovery period was uneventful, and the patient has remained asymptomatic for 2
      years. Physicians must be aware of radiolucent foreign bodies. Computed
      tomography is very helpful in establishing the diagnosis of radiolucent foreign
      body, mediastinal abscess, and spondylodiscitis.

PMID- 8861485
TI  - 'Pilonidal appendicitis' or 'the hair of the dog': an unusual case of foreign
      body perforation of the appendix.
AB  - Perforation is common in the young preschool child who has appendicitis, and can
      occur as the result of an ingested foreign body. A variety of objects have been
      incriminated. The present report describes a case in which the appendiceal wall
      was pierced by a stiff canine hair.

PMID- 8861486
TI  - Hairy polyp of the oropharynx: case report and literature review.
AB  - Hairy polyp of the oronasopharynx is an uncommon developmental malformation that
      is most frequently seen as a pedunculated tumor in the neonate. Derived from the
      ectoderm and mesoderm, this benign tumor generally has been classified as
      dermoid. The clinical presentation is dependent on the polyp's size and location.
      A full-term girl was evaluated for an oral mass that was first noted at the time
      of birth. Evaluation showed a 5- x 2.5-cm soft, nontender, skin-covered mass that
      protruded from the oral cavity. During surgery, it was noted that the stalk was
      attached to the superior pole of the left tonsil. The histology of the mass was
      consistent with a hairy polyp. Knowledge of this type of malformation facilitates
      early intervention and avoids significant morbidity.

PMID- 8861487
TI  - An unusual cause of penetrating cardiac injury in a child.
AB  - The authors report on a 7-year-old boy who suffered an unintentional penetrating
      cardiac injury while misusing a lawn toy in a predictable way. The boy was
      hemodynamically stable, with abdominal pain and tenderness. The pericardial
      effusion was first noted on upper abdominal computerized tomographic images and
      was confirmed by echocardiography. A puncture wound of the anterior right
      ventricle was found. As in this case, children may not have the typical signs and
      symptoms of cardiac tamponade, making the diagnosis difficult and delaying
      appropriate care. This child's injury could have been prevented through increased
      parental supervision or a modified toy design that takes into account predictable
      patterns of misuse.

PMID- 8861488
TI  - Congenital anorectal teratoma: report of a case.
AB  - This is the first reported case of congenital anorectal teratoma. Total
      disconnection from the coccyx and mucomembranous covering distinguish this tumor
      from the more common sacrococcygeal teratoma. Complete surgical excision is
      important to avoid recurrence or malignant transformation.

PMID- 8861489
TI  - Postnatal intussusception in a premature infant, causing jejunal atresia.
AB  - The authors report on a 5-week-old boy who presented with bilious gastric
      aspirates. He became intolerant to feedings after 1 week of adequate feeding and
      passage of stools. Based on clinical and radiological findings, the diagnosis of
      intestinal obstruction was made. During laparotomy, atresia of the proximal
      jejunum was found. The lumen of the distal segment contained an intussusceptum.
      The blind ends were resected, and end-to-end anastomosis was performed.

PMID- 8861490
TI  - Multifocal mesenchymal hamartoma of the chest wall in infancy.
AB  - The authors report on an infant who had multifocal mesenchymal hamartoma of the
      right posterior chest wall. The tumors were found incidentally, on a chest
      radiograph, during routine evaluation for upper respiratory tract infection.
      Resection of both lesions with chest wall reconstruction was performed, with a
      good result. Only 46 cases of this unusual tumor have been reported previously,
      and only two of them were multifocal.

PMID- 8861491
TI  - Laparoscopic esophagomyotomy for achalasia in children.
AB  - Achalasia is an uncommon condition in children. The authors report on two
      children who were evaluated and treated with laparoscopic esophagomyotomy. A 6
      port technique was used, with five 5-mm ports and one 10-mm port. During the
      procedure, esophagoscopy was performed simultaneously, which provided esophageal
      distension for easier dissection and aided the surgeon by documenting when a
      complete myotomy had been accomplished. The patients' symptoms have resolved, and
      no postoperative complications have developed. Laparoscopic esophagomyotomy can
      be performed safely in children and is an effective approach for treatment of
      this disorder. Its advantages over the open approach include shorter
      hospitalization and less discomfort.

PMID- 8861493
TI  - Segmental defect of the intestinal musculature of a newborn: evidence of acquired
      pathogenesis.
AB  - Two cases of premature newborns with a segmental defect of the intestinal
      musculature are presented. The clinical diagnoses were intestinal obstruction and
      perforation, respectively. Emergency laparotomy was performed. In the first case,
      this showed a dilated loop of ileum and proximally dilated small bowel. The
      second case had ileal perforation with marked pneumoperitoneum. Pathological
      examination showed multifocal partial or complete absence of the muscularis
      propria, with relative preservation of the remaining components of the bowel wall
      in both cases. In addition, foci of recent muscular necrosis was noted in case 1,
      and early replacement fibrosis in case 2. These findings suggest that the muscle
      defect was secondary to muscle injury rather than a primary absence of muscle.
      The different theories of pathogenesis are discussed.

PMID- 8861492
TI  - Peroperative (123)I-MIBG scan using a sterile probe for staging and resection of
      neuroblastoma in children.
AB  - Two children with neuroblastoma were treated at Bristol Children's Hospital. One
      had primary resection of a right adrenal tumor; the other had resection of a
      secondary lymph node located in the left supraclavicular fossa. In both cases,
      the patients received 123(I)-meta-iodobenzylguanidine (MIBG) preoperatively, and
      a sterilizable, hand-held Cadmium-Telluride (CdTe) solid-state detector was used
      for localization of the tumor. The surgical procedure was facilitated
      significantly by this peroperative radioisotope-guided technique.

PMID- 8861494
TI  - Thoracic mesenchymoma of infancy.
AB  - Mesenchymoma of the chest wall is rare in infancy and can be easily mistaken for
      a malignant tumor. It is a distinct pathological entity that presents at birth or
      during infancy as self-limiting expansile intraosseous lesions involving the body
      of one or more ribs. Histologically, it is a benign focal overgrowth of normal
      skeletal elements. Two such cases are presented.

PMID- 8861495
TI  - Renal cell carcinoma in association with tuberous sclerosis in children.
AB  - Tuberous sclerosis, a genetically transmitted multisystem neurocutaneous
      disorder, is associated with renal lesions in 50% of cases. The expected lesions
      are angiomyolipomas or renal cysts; renal cell carcinoma has been encountered in
      adults who have tuberous sclerosis, but is very rare in children. The authors
      report the case of a 5-year-old girl with tuberous sclerosis for whom atypical
      computed tomography findings led to the diagnosis of renal carcinoma at an early
      age. This experience suggests that children with tuberous sclerosis may need
      earlier screening.

PMID- 8861496
TI  - Late recurrence of Hodgkin's disease after partial splenectomy.
AB  - The use of laparotomy and splenectomy for staging purposes in patients with
      Hodgkin's disease (HD) gained popularity in the early 1970s. Accurate staging and
      more effective treatment regimens, including combined chemotherapy and
      irradiation, have resulted in improved patient survival rates. Similarly, an
      increased number of late complications have been reported, including the
      development of thyroid disease, second malignancies, and septic complications
      related to splenectomy. Partial splenectomy has been proposed as one method of
      preventing overwhelming postsplenectomy sepsis. The authors present a case of
      recurrence of HD, which occurred in the splenic remnant 13 years after the
      initial treatment. This case demonstrates that the spleen is a potential for
      recurrent intraabdominal Hodgkin's disease after partial splenectomy; thus, the
      use of partial splenectomy for HD should be discouraged.

PMID- 8861497
TI  - Pancreatitis caused by a gastric duplication communicating with an aberrant
      pancreatic lobe.
AB  - Developmental anomalies of the pancreas and its ductal drainage system are an
      important cause of pancreatitis. Patients with such anomalies require appropriate
      surgical intervention. This report concerns an uncommon foregut anomaly that
      causes pancreatitis. A 9-year-old girl had recurrent pancreatitis secondary to a
      gastric duplication communicating with an aberrant pancreatic lobe. Appreciation
      of the relevant anatomy led to successful surgical management of the
      pancreatitis.

PMID- 8861498
TI  - New strategies in oral immunotherapy for diabetes prevention.

PMID- 8861499
TI  - Interactions between glucose and FFA metabolism in man.

PMID- 8861500
TI  - Hypertriglyceridemia and its metabolic consequences as a risk factor for
      atherosclerotic cardiovascular disease in non-insulin-dependent diabetes
      mellitus.

PMID- 8861501
TI  - Vitamin D analogues in insulin-dependent diabetes mellitus and other autoimmune
      diseases: a therapeutic perspective.

PMID- 8861502
TI  - Modification of lipoproteins in diabetes.

PMID- 8861510
TI  - Affect and memory in depression: evidence of better delayed recall of positive
      than negative affect words.
AB  - It is widely accepted that depressives focus on negative memories, and forget or
      repress positive memories (showing a mood-congruent affective tendency). Normals
      have an opposite positive bias in memory ('Pollyanna tendency'). Research
      evidence for depressives' negative bias in memory comes mainly from studies of
      retrieval of personal experiences during depression, or from studies of such
      retrieval during induced mood. In the present study, the hypothesis that
      depressives encode and remember negative emotion materials better than other
      materials was tested. Contrary to the hypothesis, the results showed that
      severely depressed patients remembered more positive affect than negative affect
      words, after a 2-day delay. Depressives' overall memory performance and rate of
      forgetting were poor, similar to schizophrenics', and worse than normals'. The
      results suggest that, while memory performance during a depressive episode is
      poor, the memory consolidation process for affective information is normal.
      Unlike in schizophrenia, it does not select negative emotion materials. This
      conclusion is not incongruent with the finding that depressives show mood
      congruent retrieval for previously learnt personal (experiential) information.
      The consolidation of non-personal (nonexperiential) positive affect materials
      during depression may provide a clue as to the mechanism of recovery in
      depression, and the lack of such recovery in schizophrenia.

PMID- 8861511
TI  - Subclassifications in eating disorders and obesity: a comparative study of an
      Italian sample.
AB  - The purpose of this study is to examine differences between eating disorder
      subgroups, including obese patients, in a large Italian sample seen at a
      specialist clinic. All patients (n=263) who consecutively contacted the
      University Eating Disorder Outpatient Clinic of Padua were divided into subgroups
      according to the literature. Different subgroups were compared according to
      clinical features, SCL-90, EAT and TFEQ scores. The study confirms the importance
      of purging, which is associated with more severe psychiatric symptoms than
      bingeing; a direct correlation between severity of psychiatric symptoms and
      duration of eating disorder was found. Among obese patients the bingers are
      distinguished from the nonbingers by a higher degree of eating and psychological
      distress and a greater number of dieting attempts.

PMID- 8861512
TI  - Cross-cultural study of schizophrenia.
AB  - Researchers have used a variety of approaches to assess schizophrenic disorders
      across cultures. Of the possible ways of studying cultural variations, the one
      most typically employed involves the accumulation of data in geographically
      isolated settings and indigenous situations. Another method is through
      comparative studies of people of various backgrounds living in the same social
      and geographical environment. This opportunity is provided by immigrants of
      diverse origins living in the same community. Ninety schizophrenic patients
      (according to DSM-III-kappa criteria) participated in this study, aged between 18
      and 35 years. Three groups were constituted. The first population consisted of
      second-generation North Africans living and raised in France, the second of
      native French patients, and the third population consisted of schizophrenic
      patients living and being raised in North Africa (Algeria), their native country.
      This study showed that, for the symptoms evaluated, schizophrenic patients from
      Maghreb have few clinical differences from patients of French origin. Thus,
      cultural origins do not seem to be of major influence. These results are in
      concordance with those of the International Pilot Study of Schizophrenia based on
      a larger international population.

PMID- 8861513
TI  - Psychopathology in patients with schizophrenia and substance abuse: a comparative
      clinical study.
AB  - In a 3-month epidemiologic survey at the Psychiatric Clinic of the University
      Hospital Hamburg-Eppendorf, a total of 372 patients between 18 and 60 years of
      age were screened with a variety of clinical psychiatric tests. Of the entire
      group, a subgroup of 180 patients was placed into one of four index groups:
      schizophrenics with first-rank symptoms and with (n=47) or without (n=52)
      concomitant past or acute use of psychotropic substances; alcoholics (n=63), and
      patients with alcoholic psychosis (n=18). In almost all areas examined, the group
      of schizophrenics with substance abuse was revealed to be a severely disturbed
      subgroup of schizophrenics with a long history of disease. Particularly with
      respect to psychopathology, there was an increase in depressive and suicidal
      tendencies.

PMID- 8861514
TI  - Schizophreniform disorder: a 1-year follow-up study.
AB  - The study reports the preliminary data from a small 12-patient sample assessed at
      the time of their first psychotic episode and diagnosed as having a
      schizophreniform disorder. After a 1-year follow-up period all the patients were
      newly evaluated on clinical and global functioning variables, using clinical
      diagnosis as an outcome measure. A diagnostic stability in the schizophrenic
      spectrum was found.

PMID- 8861515
TI  - Obsessive-compulsive phenomenon in a so-called 'symptomarme schizophrenie': from
      the viewpoint of structural dynamics in defense mechanisms.
AB  - (1)'Antieidos' is a formlessness that results from the reverse intentionality of
      the life formation and is considered to be a principle of obsessive psychosis.
      'Internal emptiness' is supposed to exist in the nucleus of schizophrenia.
      'Antieidos' and 'internal emptiness' are in close proximity, partly overlapping
      each other. Obsessive psychosis and some types of simple schizophrenia are
      considered to have a common intentionality for the obsessive-compulsive
      phenomenon from the viewpoint of defensive structural dynamics. (2) The obsessive
      compulsive phenomenon and the hypochondriacal phenomenon that coexist in simple
      schizophrenia are considered to be a 'noema' (something in which a meaning is
      given to the intended experience) that results from 'noesis' (action of
      consciousness seen in the intended experience) which has a defensive
      intentionality and as a result masks the basic disturbance in schizophrenia.
      Complementarity between the obsessive-compulsive phenomenon and the
      hypochondriacal phenomenon structured in this way can form one type of disease in
      the nonself-introspective category of simple schizophrenia.

PMID- 8861516
TI  - Dysmorphophobia: differential-diagnostic aspects.
AB  - The case of a patient presenting with a depressive-suicidal syndrome and
      dysmorphophobia, which also showed a delusional character, is discussed
      concerning the differential-diagnostic difficulties. The nosology of the disorder
      is discussed especially regarding the variants in the new classification systems.

PMID- 8861517
TI  - Prodromal symptoms in obsessive-compulsive disorder.
AB  - Prodromal symptoms were investigated in 30 patients with obsessive-compulsive
      disorder. The large majority of patients (93%) reported at least one prodromal
      symptom before disease onset. Generalized anxiety, irritability, indecision,
      phobic and somatic anxiety occurred in about half of patients. Also common were
      depressive symptoms such as fatigue, lowered self-esteem, depressed mood,
      pessimism, impaired work, and guilt. The results suggest a close association of
      obsessions and compulsions with affective symptoms.

PMID- 8861518
TI  - Maternal obsessions of child sexual abuse.
AB  - Very few cases exist in the literature of maternal obsessional thoughts of child
      sexual abuse. Two such cases are described of mothers who experienced obsessional
      thoughts in the puerperium which concerned sexually abusing their own children.
      Obsessional thoughts of a sexual nature have been shown to occur commonly--in
      over 25% of those diagnosed with obsessive-compulsive neuroses. These obsessional
      thoughts concern actions which are usually identified as going against the
      sufferer's own value systems or involving sexual perversions. Obsessional
      thoughts of sexually abusing family members are rarely documented; there are no
      reports of obsessional thoughts experienced by a mother in the puerperium
      concerning sexual abuse of her own children. We report two cases of mothers
      suffering from obsessions of this nature at The Mother and Baby Unit (MBU), Queen
      Elizabeth Psychiatric Hospital, Birmingham.

PMID- 8861519
TI  - Factor analysis of the French version of the 20-Item Toronto Alexithymia Scale
      (TAS-20).
AB  - A French version of the Toronto Alexithymia Scale-20 Items (TAS-20) was factor
      analyzed on a sample of 263 university students and its factor solution analyzed
      along with the studies using the Canadian version. Our results show a two-factor
      solution where the items rating the difficulty to identify feelings and the items
      rating the difficulty to describe feelings constitute a sole factor contrary to
      the Canadian version. These data are reviewed in the context of previous research
      and offer two subscales for future investigations utilizing the TAS-20.

PMID- 8861520
TI  - Menu for successful antireflux surgery.

PMID- 8861521
TI  - Stool markers for colorectal cancer screening: future considerations.
AB  - Stool screening for colorectal neoplasia has the important advantages of
      noninvasiveness and affordability over other available screening approaches.
      However, better markers are needed to improve the sensitivity and specificity of
      stool screening. A functional classification of stool markers is proposed, based
      on the mode of luminal marker entry, which may be useful in considering
      alternative markers.

PMID- 8861522
TI  - Treatment of ascites: old and new remedies.
AB  - Ascites is a common complication of chronic liver disease. Treatment of the
      underlying liver disease with modalities such as abstinence from alcohol in
      Laennec's cirrhosis, phlebotomy in hemochromatosis, copper removal in Wilson's
      disease, and steroids in autoimmune liver disease, can improve survival in many
      patients. In addition, therapy of ascites alleviates the symptoms and improves
      the quality of life of the patients, and probably decreases the incidence of life
      threatening conditions including spontaneous bacterial peritonitis and
      hepatorenal syndrome. The mean survival rate at 2 years is approximately 50%.
      Precipitating factors such as gastrointestinal bleeding, nonsteroidal anti
      inflammatory drugs and infections, should be identified, since most of them can
      be corrected. Most cirrhotics with ascites can be managed with a 'step-by-step'
      approach, including dietary salt restrictions, aldosterone antagonists, and loop
      diuretics. When tense or refractory ascites is present, large-volume paracentesis
      is safe and effective. Peritoneovenous shunting (i.e. Denver, LeVeen) is less
      frequently used because of perioperative morbidity and mortality, and thrombotic
      complications with occlusion of the stent. Reinfusion of concentrated ascites is
      of potential benefit and has been used in Europe. Transjugular intrahepatic
      portosystemic shunt (TIPS) is an alternative procedure performed by
      interventional radiologists that allows decompression of portal hypertension. In
      many cases, ascites is improved after TIPS, but long-term randomized trials for
      tense or refractory ascites comparing TIPS with standard therapy are not
      conclusive. Liver transplantation is the ultimate step for the treatment of
      ascites, providing the cure for the underlying liver disease as well.
      Transplantation is indicated when quality of life of the patient is impaired due
      to recurrent episodes of ascites, or in the presence of spontaneous bacterial
      peritonitis and hepatorenal syndrome.

PMID- 8861523
TI  - Extrahepatic manifestations of hepatitis C.
AB  - Shortly after the discovery of the hepatitis C virus, it was realized that this
      infectious agent caused more than just liver disease. A remarkable array of
      extrahepatic manifestations of hepatitis C has now been described. Many of these
      associated syndromes implicate the hepatitis C virus as a mediator of
      autoimmunity or of immune complex formation. These disorders include mixed
      essential cryoglobulinemia, autoimmune hepatitis, glomerulonephritis,
      thyroiditis, and possibly Sjogren's syndrome. The hepatitis C virus has also been
      strongly linked to two skin disorders: prophyria cutanea tarda and lichen planus.
      Other possible hepatitis-C-associated diseases described in the literature
      include idiopathic pulmonary fibrosis, IgA deficiency. Mooren's corneal ulcers,
      Behcet's syndrome, polyarthritis, Guillain-Barre' syndrome, idiopathic
      thrombocytopenic purpura, and others. A number of these reported diseases have
      either responded to or been cured by a therapeutic course of alpha interferon.
      This report discusses the reported extrahepatic manifestations of hepatitis C as
      of mid-1995.

PMID- 8861524
TI  - Indications, benefits and outcome of laparoscopic Nissen fundoplication.
AB  - The advent of laparoscopic fundoplication has catalyzed renewed interest in the
      surgical treatment of gastroesophageal reflux disease (GERD), and continues the
      evolution of surgical treatment begun by Phillip Allison in the early 1950s.
      Clinical observations of the natural history of GERD suggest a high risk group of
      approximately 25% of patients who develop recurrent and progressive disease,
      often despite medical therapy. These patients should be considered candidates for
      early surgical intervention. Early clinical studies of laparoscopic
      fundoplication document successful relief of reflux symptoms in nearly 90% of
      patients, results nearly identical to its open counterpart. This review focuses
      on the indications and patient selection for, as well as the technique and
      outcome of laparoscopic Nissen fundoplication.

PMID- 8861525
TI  - The changing role of surgery for sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is a chronic cholestatic disease that may
      ultimately progress to hepatic parenchymal dysfunction and death from premature
      liver failure. Symptomatic patients should undergo radiological evaluation to
      exclude secondary causes of cholangitis and to evaluate the extent and location
      of biliary ductal disease. A percutaneous liver biopsy is advisable in any
      patient with clinical or biochemical evidence of cirrhosis. Patients with diffuse
      ductal involvement should initially receive medical treatment, preferably in a
      center conducting prospective clinical trials. Liver transplantation should be
      considered the initial procedure in primary sclerosing cholangitis patients with
      diffuse ductal involvement, complications of cirrhosis or deteriorating liver
      function. Nontransplant procedures should be restricted to symptomatic patients
      with a dominant extrahepatic stricture. In properly selected patients, effective
      and durable palliation of symptoms can be anticipated with biliary enteric
      drainage. Many currently available techniques obviate the need for longterm
      transanastomotic stenting, thus minimizing the risk of recurrent cholangitis and
      the need for repeated tube changes. These patients may also be candidates for
      percutaneous or endoscopic balloon cholangioplasty. Liver transplantation should
      also be considered in patients with a dominant stricture and histologic evidence
      of biliary cirrhosis or hepatic deterioration following a nontransplant
      procedure.

PMID- 8861526
TI  - Enteric immunization: promises and challenges.
AB  - Immunization to prevent many intestinal infections is inadequate because most
      available vaccines are given parenterally, a route that does not effectively
      stimulate the intestinal immune system. Thus, investigators are pursuing several
      strategies for achieving enteric protection through oral immunization. The most
      promising approaches are the incorporation of immunogens into microparticles for
      protection and enhanced uptake of the immunogen by intestinal lymphoid tissues,
      the genetic manipulation of microorganisms, and the use of mucosal adjuvants. The
      achievement of effective oral immunization against intestinal infections could
      lead to control of serious diarrheal illnesses, which still are a major worldwide
      health problem.

PMID- 8861527
TI  - Emerging role of endoscopic variceal band ligation in the treatment of esophageal
      varices.
AB  - Bleeding from esophageal varices is the most catastrophic complication of portal
      hypertension. The associated high morbidity and mortality have necessitated the
      development of safe and efficacious therapeutic modalities. In recent years,
      endoscopic band ligation of esophageal varices has proved to be a useful tool in
      the control of acute variceal bleeding and the prevention of recurrent bleeding.
      This endoscopic technique is faster than sclerotherapy in obliterating esophageal
      varices, and is associated with significantly lower local esophageal
      complications. In the forthcoming years, endoscopic band ligation is expected to
      gain wider popularity as a definitive therapy for bleeding varices.

PMID- 8861528
TI  - Isolated gastric varices associated with spontaneous splenorenal shunt.

PMID- 8861529
TI  - Fleroxacin overview.
AB  - Fleroxacin is a new oral and intravenous trifluorinated 4-quinolone, which acts
      by inhibiting the essential bacterial enzyme DNA gyrase. Fleroxacin exhibits a
      broad spectrum of action, characterized by pronounced activity against aerobic
      gram-negative bacteria, but also against gram-positive pathogens such as
      staphylococci. Fleroxacin is distinguished by its excellent bioavailability, high
      concentrations in the plasma and other body fluids, good tissue penetration, and
      a long half-life of 10-12 h, thus allowing once-a-day administration. A single
      oral dose of 400 mg fleroxacin is effective in uncomplicated cystitis in women,
      uncomplicated gonococcal infections, bacterial enteritis, and traveler's
      diarrhea. A single daily dose of 200 mg administered for 3 days is effective in
      uncomplicated urinary tract infection (UTI), while longer treatment and higher
      doses may be required in acute uncomplicated pyelonephritis and complicated UTI.
      Skin, soft tissue, bone and joint infections, and lower respiratory tract
      infections including exacerbation of chronic bronchitis and non-pneumococcal
      pneumonia are further indications for fleroxacin.

PMID- 8861530
TI  - Single oral dose treatment of uncomplicated urinary tract infection in women.
AB  - A single oral dose of an antimicrobial agent is as effective as a conventional 3
      day course for the treatment of uncomplicated lower urinary tract infections. A
      case history of a young woman with recurrent cystitis is presented to demonstrate
      this approach to the management of a common clinical problem. The place of
      antimicrobial prophylaxis is also discussed.

PMID- 8861531
TI  - Fleroxacin in complicated urinary tract infections.
AB  - The clinical evaluation of antimicrobial agents for the treatment of urinary
      tract infections (UTIs) requires clinically useful categorization of patients
      plus concurrent laboratory diagnosis. Appropriate diagnostics include (1) proper
      collection techniques, (2) quantitative urine culture, (3) urinalysis to
      determine pyuria, and (4) radiological, urological and gynecological evaluation.
      Categorization of patients suffering from UTIs should take into consideration (1)
      the site of infection, (2) the clinical presentation, (3) the frequency of
      infections, and (4) the coexistence of complicating factors. UTIs in men and
      older women are mostly complicated. The characterization of a UTI as complicated
      or uncomplicated is important since in the former condition, multiresistant
      nosocomial microorganisms are frequently encountered. Experience with fleroxacin
      200 or 400 mg once daily (o.d.) in > 1,000 patients with complicated UTIs in
      noncomparative and comparative trials with other quinolones and cephalosporins
      has been very promising, with overall clinical and bacteriological cure rates of
      86-95 and 89-95%, respectively. As with other quinolones, relapses and
      superinfections were mostly attributed to Enterococcus, Staphylococcus and
      Pseudomonas spp. The reported results make oral o.d. fleroxacin appropriate as an
      alternative to parenteral antimicrobials or for intravenous-to-oral switch
      therapy in complicated UTIs.

PMID- 8861532
TI  - Quinolone prophylaxis in transurethral surgery.
AB  - In transurethral surgery, there is much controversy about the benefit of
      antimicrobial prophylaxis. Any urinary tract infection should be treated before
      proceeding with a transurethral operation. There is growing evidence that
      antimicrobial prophylaxis is also beneficial in cases with preoperatively sterile
      urine. A single dose or short-term prophylaxis appears to be sufficient. As newer
      fluoroquinolones reach very high tissue concentrations, have a suitable
      antimicrobial spectrum to cover most uropathogens and can be administered orally,
      these new drugs represent an attractive choice for prophylaxis in transurethral
      surgery.

PMID- 8861533
TI  - Quinolones in everyday clinical practice: respiratory tract infections and
      nosocomial pneumonia.
AB  - Currently available fluoroquinolones have established their value in the
      treatment of lower respiratory tract infections due to gram-negative rods and
      Staphylococcus aureus. The fact that these drugs are absorbed (and well
      tolerated) when given orally is a major positive feature. The once daily dosage
      of fleroxacin [400 mg once daily intravenously (i.v.) for 2-4 days followed by
      oral doses of 400 mg for up to 10 days] was compared with twice daily
      ciprofloxacin (400 mg twice daily i.v. for 2-4 days followed by oral doses of 2 x
      500 mg for up to 10 days) for treatment of inpatients with pneumonia confirmed by
      clinical signs and chest X ray. To date, 93 evaluable patients have been enrolled
      in this study. Clinical cure and improvement rates were 73.3% in the fleroxacin
      group and 79.2% in the ciprofloxacin group. The rate of adverse clinical or
      laboratory events was similar in both study groups.

PMID- 8861534
TI  - Quinolones in gastrointestinal infections.
AB  - Fluoroquinolones are efficient antimicrobial drugs for the treatment of enteric
      fever, shigellosis, Escherichia coli diarrhea, cholera, and traveler's diarrhea.
      They also play a role in the therapy of yersiniosis, campylobacteriosis, and
      intestinal salmonellosis. A single dose of quinolones has been effective in the
      treatment of traveler's diarrhea and cholera. Uncomplicated typhoid fever was
      cured by norfloxacin, pefloxacin, and ofloxacin 400 mg twice daily (b.i.d.) for 7
      14 days or ciprofloxacin 500 mg b.i.d. for 10 days. A single daily dose of 400 mg
      fleroxacin for 3 days has been shown to be effective in this indication. A few
      reports suggest that the newer quinolones can eliminate the carrier state. The
      efficacy of quinolones in the prophylaxis and treatment of intra-abdominal
      infections following abdominal surgery requires further investigation.

PMID- 8861535
TI  - On the relationship of thermodynamic parameters with the buried surface area in
      protein-ligand complex formation.
AB  - Prediction of thermodynamic parameters of protein-protein and antigen-antibody
      complex formation from high resolution structural parameters has recently
      received much attention, since an understanding of the contributions of different
      fundamental processes like hydrophobic interactions, hydrogen bonding, salt
      bridge formation, solvent reorganization etc. to the overall thermodynamic
      parameters and their relations with the structural parameters would lead to
      rational drug design. Using the results of the dissolution of hydrocarbons and
      other model compounds the changes in heat capacity (delta C(p)), enthalpy (delta
      H) and entropy (delta S) have been empirically correlated with the polar and
      apolar surface areas buried during the process of protein folding/unfolding and
      protein-ligand complex formation. In this regard, the polar and apolar surfaces
      removed from the solvent in a protein-ligand complex have been calculated from
      the experimentally observed values of changes in heat capacity (delta C(p)) and
      enthalpy (delta H) for protein-ligand complexes for which accurate thermodynamic
      and high resolution structural data are available, and the results have been
      compared with the x-ray crystallographic observations. Analyses of the available
      results show poor correlation between the thermodynamic and structural
      parameters. Probable reasons for this discrepancy are mostly related with the
      reorganization of water accompanying the reaction which is indeed proven by the
      analyses of the energetics of the binding of the wheat germ agglutinin to
      oligosaccharides.

PMID- 8861536
TI  - Practical considerations regarding the use of streptolysin-O as a permeabilising
      agent for cells in the investigation of exocytosis.
AB  - Streptolysin-O is widely used in cell biological investigations in order to make
      large (>12 nm) pores in the plasma membrane and so to render the cytosol directly
      accessible to experimental manipulation. We have compared the effect of
      streptolysin-O commercially formulated (Murex Diagnostics) as a diagnostic
      reagent in pathology with two pure reagents (a conventional purified protein, and
      a recombinant protein generated in E.coli) on exocytotic secretion from mast
      cells. For mast cells permeabilised by streptolysin obtained from the commercial
      source, exocytosis (of beta-D-N-acetylglucosaminidase) is dependent on provision
      of both Ca(2)+ and a guanine nucleotide. In contrast, for cells permeabilised by
      either of the two pure proteins, a substantial extent of Ca(2)+-independent
      exocytosis can be elicited. When the Murex material is subject to dialysis or
      ultrafiltration, some secretion can be induced in the absence of Ca(2)+,
      indicating a modulatory function of the low mol wt additives of formulation,
      mainly phosphate and cysteine. However, Ca(2)+-independent exocytosis is still
      manifest when the pure proteins are reconstituted with ultrafiltrates from the
      Murex material. These observations indicate that reagents used to permeabilise
      cells should be characterised thoroughly and used with great care. Confirmation
      that the cytolytic activity of the Murex material derives from a cholesterol
      directed factor was demonstrated by inhibition of exocytosis when red blood cell
      derived (and hence cholesterol containing) sonicated liposomes were provided.

PMID- 8861537
TI  - Modulation of islet G-proteins, alpha-glucosidehydrolase inhibition and insulin
      release stimulated by various secretagogues.
AB  - Guanine nucleotide-binding proteins (G-proteins) are known to act as important
      modulators of insulin release from the islets of Langerhans. We have recently
      found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of
      intestinal alpha-glucosidehydrolase activity, is a powerful inhibitor of glucose
      induced insulin release. With the use of isolated mouse islets the present
      investigation was performed in a primary attempt to elucidate whether this
      inhibitory mechanism in some way was linked to the beta-cell G-protein system.
      Treatment of freshly isolated islets with pertussis toxin (PTX), which is known
      to inactivate the G (i)-proteins, abolished the inhibitory effect of the alpha(2)
      adrenoceptor agonist clonidine on insulin release stimulated by the
      phosphodiesterase inhibitor IBMX in the presence of the protein kinase C
      activator TPA and even changed it into an increase. Emiglitate did not display
      any inhibitory action on insulin release induced by these secretagogues.
      Similarly, clonidine-induced inhibition of glucose stimulated insulin release was
      reversed by PTX. However, PTX did not influence the suppressive action of
      emiglitate on glucose-induced insulin secretion. In contrast, the adenylate
      cyclase activator forskolin totally abolished the inhibitory effect of
      emiglitate, but not that of the glucose analogue mannoheptulose, on glucose
      induced insulin release. Moreover, the stimulatory effect of forskolin and
      cholera toxin (CTX) (activator of G (s)-proteins) on the secretion of insulin was
      markedly enhanced in the presence of emiglitate. In conclusion, our results
      suggest that the inhibitory effect of emiglitate on glucose-induced insulin
      release is not directly related to the G(s)-proteins, but most likely exerted
      solely through the selective suppression of lysosomal aglucosidehydrolase
      activity, a step in between the proximal and the distal G(i)-proteins, in glucose
      induced stimulus-secretion mechanisms. Our data also suggests that the inhibitory
      action of emiglitate on glucose stimulated insulin release can be compensated for
      by an increased sensitivity of the cyclic AMP-protein kinase A pathway. Hence,
      emiglitate might indirectly elicit an increased activity of the G(s)-proteins to
      facilitate the secretory process.

PMID- 8861538
TI  - Short-term inhibition of the energy metabolism affects motility but not surface
      properties of sperm cells.
AB  - Centrifugal countercurrent distribution (CCCD) in aqueous two-phase systems has
      been proven to be a useful method to study subtle surface properties of
      spermatozoa. The present work shows that a short-term inhibition of the energy
      metabolism of sperm cells effected by incubating bovine sperm cells with KCN or
      ouabain, did not account for changes in the cell surface properties, as assessed
      either by estimation of the cell viability or by CCCD analysis. However, the
      short-term inhibition of energy metabolism provoked a clear decrease of cell
      motility, suggesting that a drop of cellular ATP levels brings about a rapid
      decrease of motility followed by a very delayed effect on cell surface
      properties. The relevance of these results on the handling of sperm and on the
      understanding of the molecular events underlying asthenospermia is discussed.

PMID- 8861539
TI  - Electrical conductivity dispersion as a probe of membrane modifications in mouse
      polyomavirus infected cells in culture.
AB  - In this report we investigate the inhibition of membrane conductivity, due to the
      murine polyomavirus infection in permissive cells in culture. We define
      experimental conditions to have reproducible results and demonstrate that the
      intensity of the effects on the cell membrane, depends upon the virus titer used
      in the infection. Finally, the virus dependent effects disappear if the infection
      is performed in the presence of a drug that inhibits polymavirus DNA replication.

PMID- 8861540
TI  - Aluminium-induced bone disease in uremic rats: effect of deferoxamine.
AB  - We have previously established a rat model of chronic uremia, which is suitable
      to investigate the effect of various treatment modalities on renal osteodystrophy
      [1]. After four months subsequent to 5/6 nephrectomy, some animals were treated
      by gavage for 9 weeks with tap water (controls), or with aluminium (Al-citrate) 3
      x 25 mg/week/kg b.wt +/- subsequent deferoxamine (DFO) 3 x 50 mg/week/kg b.wt.
      for 4 weeks. At termination of the study, serum clinical chemistry, femoral
      chemical composition and mechanical properties, calvarial parathyroid hormone
      (PTH)-elicited adenylate cyclase (AC) and phospholipase C (PLC) activities, cross
      sectional femoral area, as well as bone histomorphometry, were analyzed. Animals
      given Al displayed moderately enhanced serum Al and bone Al accumulation,
      however, DFO-treatment did not fully alleviate bone Al retainment. A small
      increase in serum PTH was seen in all animals rendered uremic. Furthermore, a
      marked fall in serum alkaline phosphatase (ALP) below normal controls was
      observed in Al +/- DFO-treated animals compared with uremic controls. The uremic
      condition led to reduced femoral ratios of hydroxyproline (HYP) over Ca(2+) and
      phosphate (P(i)), while Al-intoxication alone enhanced femoral Hyp contents above
      values seen for normal controls. The protracted ureamia caused a deterioration of
      long bone resilience and brittleness, however, Al +/- DFO-treatment seemed to
      normalize the latter. Contrastingly, Al +/- DFO-gavage enhanced time to fracture.
      Uremic rats intoxicated with Al showed a complete loss of calvarial PTH-sensitive
      AC and PLC activities. DFO-treatment normalized PTH-elicited PLC, while PTH
      susceptible AC remained super-normal. Al apparently exerts a long term down
      regulation of both PTH-sensitive signaling systems as evidenced by studies of rat
      UMR 106 osteosarcoma cells in culture. The uremic condition enhanced endosteal
      bone resorption as shown by femoral shaft dimension analysis, while Al +/- DFO
      treatment insignificantly reversed the condition. Finally, histomorphometrical
      analyses showed that DFO-administration tended to normalize aberrant trabecular
      bone volume, while rectifying both bone resorption and degree of mineralization.
      In conclusion, we assert that Al-intoxication hampers both processes (i.e.
      formation and resorption) of bone turnover, and that DFO-treatment to a certain
      extent prevents the uremia- and Al-induced bone disease in rats.

PMID- 8861541
TI  - Phospholipase C activation in rat pituitary adenoma (GH) cells.
AB  - The presence of the pertussis toxin (PTX) insensitive GTP-binding proteins (C
      proteins) G(q) alpha and/or G(11) alpha has been demonstrated in three different
      prolactin (PRL) and growth hormone (GH) producing pituitary adenoma cell lines.
      Immunoblocking of their coupling to hormone receptors indicates that G(q) and/or
      G(11) confer throliberin (TRH) responsive phospholipase C (PL-C) activity in
      these cells. The contention was substantiated by immunoprecipitation analyses
      showing that anti G(q)/11 alpha-sera coprecipitated PL-C activity. In essence,
      only G(q)/11 (but neither G(12) G(13) nor G(o)) seems to mediate the TRH
      sensitive PL-C activity, while G(o) may be coupled to a basal or constitutive PL
      C activity. Immunoblocking studies imply that the B gamma-complex also, to some
      extent, may stimulate GH(3) pituitary cell line PL-C activity. Finally, the
      steady state levels of G(q)/(11) alpha mRNA and protein were down regulated upon
      long term exposure of the GH(3) cells to TRH (but not to vasoactive intestinal
      peptide = VIP).

PMID- 8861542
TI  - Current knowledge and future prospects for the use of HIV protease inhibitors.
AB  - The HIV protease (or proteinase) enzyme is an essential component of the
      replicative cycle of HIV, performing the post-transitional processing of the gag
      and gag-pol gene products into the functional core proteins and viral enzymes.
      Inhibition of this enzyme leads to production of immature noninfectious viral
      progeny, and hence prevention of further rounds of infection. Structurally, the
      enzyme is a homodimer consisting of two identical 99 amino acid chains. HIV
      protease is a member of the aspartic protease family but is structurally
      dissimilar to human aspartic proteases such as renin, gastricsin and cathepsin D
      and E, suggesting the possibility of creating inhibitors with a wide therapeutic
      index. At least 6 inhibitors of HIV protease are currently in clinical
      development: saquinavir, indinavir, ritonavir, nelfinavir (AG-1343), KNI-272 and
      VX-478, the first four of which have shown antiretroviral activity and acceptable
      tolerability in initial phase I/II clinical trials. Resistance or reduced
      sensitivity to the leading protease inhibitors has been reported in vivo and
      appears to be associated with loss of therapeutic effect. However, resistance
      patterns appear to be distinct. Treatment for 1 year with indinavir has been
      reported to lead to selection of virus in 4 patients, which was cross-resistant
      to all other leading protease inhibitors. On the other hand, a larger series of
      clinical isolates from patients receiving saquinavir alone or in combination with
      zidovudine for up to 3 years did not lead to virus cross-resistant to either
      indinavir or ritonavir. This suggests that care should be exercised in designing
      the sequence of protease usage. Additionally, differing resistance patterns may
      be used to select combinations of protease inhibitors in future trials. Data from
      studies combining protease inhibitors with nucleoside analogues suggest value in
      terms of larger and more prolonged virological and immunological marker responses
      than are observed with single agent therapy, and this is likely to be the primary
      role for protease inhibitors; both in initial combinations for patients
      commencing therapy and as add-in therapies for patients previously treated with
      antiretrovirals. However, in vitro and animal pharmacokinetic studies also give
      evidence of the possibility of combining protease inhibitors, potentially leading
      to improved bioavailability, antiviral synergy and delay in emergence of viral
      resistance.

PMID- 8861544
TI  - Management of isolated systolic hypertension.
AB  - Isolated systolic hypertension (ISH) [systolic blood pressure (SBP) > or = l60mm
      Hg with diastolic blood pressure (DBP) <90mm Hg] is the commonest form of
      hypertension in the elderly, and accounts for about 60% of all hypertensive
      conditions in the population aged over 65 years. It is associated with a
      significantly increased risk of cardiovascular and cerebrovascular morbidity and
      mortality. The landmark Systolic Hypertension in the Elderly Program (SHEP)
      study, published in 1991, has shown that lowering the SBP in elderly patients
      with ISH results in a significant reduction in cardiovascular events. These
      results have had a major impact on clinical practice in hypertension. On
      theoretical grounds, considering the pathophysiological mechanisms of ISH in the
      elderly, any drug which lowers total peripheral resistance and/or arterial
      stiffness should reduce SBP effectively in these patients. This effect has been
      observed in outcome studies and short term clinical trials using a variety of
      drugs from the 4 major antihypertensive classes: diuretics, beta(1)-blockers,
      calcium channel antagonists and ACE inhibitors. Other drugs, including alpha
      antagonists, may also be effective. In general, there is compelling evidence to
      support active treatment of any individual with an SBP > or = 160mm Hg. As in
      essential hypertension, the maximum benefit is gained by aggressive treatment of
      those individuals at highest risk because of coexisting cardiovascular risk
      factors. In these people, an SBP of 140 to 159mm Hg should be considered to be an
      indication for active management. Initial management should be by manipulation of
      lifestyle factors such as bodyweight, salt and alcohol intake and aerobic
      exercise. Drug therapy, generally well tolerated in low doses, should be
      considered if SBP remains > or = 160mm Hg, or > or = 140mm Hg in the presence of
      multiple risk factors. The choice of initial drug therapy should be influenced by
      the particular clinical situation. If there are no coexisting contraindications
      or co-indications for particular drugs, it is reasonable to begin treatment with
      a low dose of a thiazide-like diuretic, as used in the SHEP study. However, in
      short term treatment trials calcium channel antagonists and ACE inhibitors have
      been shown to lower SBP effectively and can be used in the appropriate clinical
      context. Beta-blockers appear to be less effective as monotherapy in ISH.
      Combination therapy is frequently required and can be effective and well
      tolerated if carefully chosen.

PMID- 8861545
TI  - Pharmacological treatment of psychiatric disorders in children and adolescents:
      focus on guidelines for the primary care practitioner.
AB  - This article is a practical review of the current psychopharmacological agents
      used in the treatment of child and adolescent psychiatric disorders.
      Psychostimulants such as methylphenidate, dexamphetamine and pemoline are
      effective in the control of symptoms associated with attention deficit
      hyperactivity disorder. The controlled release preparations and the adjunctive
      use of clonidine are helpful to extend stimulant effects and control adverse
      effects. Tricyclic antidepressants are helpful in individual cases of child and
      adolescent depression, but adverse effects may limit their use. Clomipramine has
      been found to be effective for childhood obsessive-compulsive disorder. Selective
      serotonin (5-HT) reuptake inhibitors (SSRIs) appear to be safer for depression
      and are also useful in obsessive-compulsive disorder. Buspirone is effective for
      the treatment of anxiety disorders in children. Newer atypical antipsychotics
      such as risperidone may have less limiting adverse effects than older
      antipsychotics in the treatment of psychosis and severe behaviour disorders, but
      the physician must be vigilant for the emergence of tardive dyskinesia. Drug
      treatment in children and adolescents must take into account the child's
      environmental influences and be part of an overall treatment plan where
      individual, familial and cultural issues are addressed.

PMID- 8861543
TI  - Opioid analgesics: comparative features and prescribing guidelines.
AB  - The term 'opioid' is a generic term for naturally occurring, semisynthetic and
      synthetic drugs which combine with opioid receptors to produce physiological
      effects and which are stereospecifically antagonised by naloxone. For clinical
      purposes, opioids can be classified according to their receptor interactions
      (agonist, partial agonist, agonist-antagonist and antagonist), the pain intensity
      for which they are conventionally used (moderate or severe), and their half-life
      (short or long). Pure agonists conventionally used for moderate pain, short and
      long half-life pure agonists conventionally used for severe pain, mixed agonist
      antagonists and partial agonist opioids are described in detail. The effective
      clinical use of opioid drugs requires familiarity with drug selection, routes of
      administration, dosage guidelines and potential adverse effects. Opioids are
      unequivocally indicated in the management of severe acute pain and moderate to
      severe pain associated with cancer. There is increasing acceptance of the role of
      opioids in the management of recurring acute pain, chronic nonmalignant pain of
      organic origin and severe neuropathic pain. The selection of opioids is
      influenced by pain intensity, pharmacokinetic and formulary considerations,
      previous adverse effects and the presence of coexisting disease. Some patients
      will require sequential trials of several different opioids before a drug which
      is effective and well tolerated is identified. Opioid agents should be
      administered by the most comfortable and convenient route that meets the specific
      needs of the patient. The regimen for opioid medications should generally provide
      around-the-clock analgesia with provision for rescue doses for the management of
      exacerbations of the pain not covered by the regular dosage. At all times,
      uncontrolled pain should be addressed by gradual increase in the opioid dose
      until either pain control is achieved or intolerable and unmanageable adverse
      effects supervene. The management of pain with opioid analgesics demands frequent
      patient assessment and a readiness to re-evaluate the therapeutic plan in the
      setting of either inadequate relief or adverse effects.

PMID- 8861547
TI  - Fosinopril: a reappraisal of its pharmacology and therapeutic efficacy in
      essential hypertension.
AB  - Fosinopril is a phosphinic acid derivative which undergoes rapid hydrolysis after
      oral administration to the active diacid ACE inhibitor fosinoprilat. Cardiotropic
      effects have been associated with the drug, and the compensatory dual elimination
      route of fosinopril via renal and hepatic systems offers an opportunity for ACE
      inhibitor treatment of hypertension in patients with renal or hepatic impairment.
      Comparative trials of monotherapy with fosinopril 10 to 40 mg/day have
      demonstrated antihypertensive efficacy equivalent to that of sustained release
      nifedipine 40 mg/day, hydrochlorothiazide 25 to 50 mg/day, enalapril 5 to 10
      mg/day amlodipine 5 to 10 mg/day and sustained release verapamil 240 to 480
      mg/day, and superior to that of isradipine 5 mg/day. The efficacy of combination
      therapy with fosinopril 10 to 20 mg/day and hydrochlorothiazide 12.5 mg/day was
      significantly superior to that of hydrochlorothiazide alone, tended to be
      superior to that of fosinopril 20 mg/day alone and was similar to that of
      sustained release nifedipine 40 mg/day alone. The combination of
      fosinopril/chlorthalidone 20 to 40/25 mg/day was as effective as
      propranolol/chlorthalidone 80 to 160/25 mg/day. The incidence of adverse effects
      associated with fosinopril is low, and cough may possibly occur less often with
      this drug than with other ACE inhibitors. Fosinopril thus offers an effective and
      well tolerated option for the treatment of hypertension in adult and elderly
      patients, including those with renal or hepatic impairment.

PMID- 8861546
TI  - Current guidelines for the treatment of acute pain in children.
AB  - Premature and full-term neonates, infants and children are capable of
      experiencing pain just like adults, and deserve aggressive treatment. Assessment
      of pain is difficult in the preverbal group. However, physiological and
      behavioural responses to noxious stimuli are well developed even in the fetus,
      and modifying these responses through treatment can affect outcome. Treatment
      options include systemic opioid and nonopioid analgesics as well as local
      anaesthetics, all of which are effective when chosen on the basis of the type and
      intensity of the pain. Dosage modification is necessary based on age and organ
      function. Nonopioid analgesics are useful supplements to reduce opioid analgesic
      dose and should be used when indicated. Drug dependence and withdrawal can be
      avoided by using the opioids appropriately and following logical weaning
      schedules after long term use of these agents. Use of needles for administering
      analgesia is still an intimidating part of the process for young children. The
      development of drugs having fewer adverse effects and noninvasive administration
      techniques will be important research priorities in the future.

PMID- 8861548
TI  - Verapamil: a review of its pharmacological properties and therapeutic use in
      coronary artery disease.
AB  - Verapamil has well proven efficacy in the treatment of patients with
      hypertension, and early studies indicated its efficacy in the treatment of
      coronary artery disease. The efficacy of verapamil relative to placebo in
      patients with stable angina pectoris is confirmed, and the drug is at least as
      effective as nifedipine, propranolol or metoprolol and of similar efficacy to
      bepridil and nicardipine when administered as a conventional or sustained release
      formulation. Verapamil is the first calcium antagonist to be shown in a double
      blind study to significantly reduce mortality and reinfarction rate after acute
      myocardial infarction in patients without heart failure. In these patients, the
      reduction in mortality achieved with verapamil was similar to that reported with
      beta-adrenoceptor antagonists, suggesting that verapamil may be a suitable
      alternative to beta-blockers as secondary prevention in patients intolerant of
      these drugs. Recurrence of stenosis in patients who successfully undergo
      percutaneous transluminal coronary angioplasty (PTCA) limits the usefulness of
      the procedure. Verapamil has recently been shown to significantly reduce the rate
      of restenosis in patients with stable angina at risk of recurrence, although
      these initial results require confirmation. Verapamil, therefore, is effective in
      the treatment of patients with stable angina pectoris, appears to be an
      alternative to beta-blockers in selected patients as late start secondary
      prevention after acute myocardial infarction and has a potential role in
      preventing recurrent stenosis after PTCA, if initial results are confirmed.

PMID- 8861549
TI  - Losartan potassium: a review of its pharmacology, clinical efficacy and
      tolerability in the management of hypertension.
AB  - Losartan potassium is an orally active, nonpeptide angiotensin II (AII) receptor
      antagonist. It is the first of a new class of drugs to be introduced for clinical
      use in hypertension. This novel agent binds competitively and selectively to the
      AII subtype 1 (AT(1)) receptor, thereby blocking AII-induced physiological
      effects. An active metabolite, E3174, contributes substantially to its
      antihypertensive effect, which persists throughout 24 hours after once-daily
      administration. In patients with mild to moderate hypertension, losartan
      potassium 50 to 100mg once daily as monotherapy lowers blood pressure to a
      similar degree to enalapril, atenolol and felodipine extended release (ER).
      Losartan potassium combined with hydrochlorothiazide reduces blood pressure
      further than either drug given separately. About one-third of patients with
      severe hypertension have responded to the combination product. Losartan potassium
      appears to be effective in elderly patients. Losartan potassium is very well
      tolerated. In clinical trials, dizziness was the only drug-related event reported
      more frequently with losartan potassium monotherapy than with placebo. First-dose
      hypotension is uncommon. An aspect of the drug's tolerability profile which may
      prove to be particularly advantageous is that it is associated with a similar
      incidence of cough to placebo in patients with a history of ACE inhibitor-related
      cough. Additionally, clinically relevant adverse metabolic effects or laboratory
      abnormalities have not been documented during losartan potassium therapy and
      renal function is preserved in patients with or without renal insufficiency. The
      adverse effect profile of the losartan potassium-hydrochlorothiazide combination
      resembles those for losartan potassium monotherapy and placebo. Long term
      tolerability data are limited (<2 years) but support the very good tolerability
      profile in shorter studies. Elements of the drug's profile yet to be assessed or
      reported fully in the literature include long term efficacy; potential to
      favourably influence cardiovascular and renovascular systems (and ultimately
      mortality) in patients with hypertension and, lastly, cost effectiveness and
      influence on quality of life. In summary, losartan potassium is the first AT(1)+
      receptor antagonist to become available for the management of hypertension and,
      as such, it is an important new antihypertensive agent. Pending long term data as
      outlined above, it is likely to find initial use in patients with mild to severe
      hypertension who are unresponsive to, or intolerant of their current therapy.
      However, with its novel mechanism of action, good efficacy and favourable
      tolerability profile, losartan potassium is well placed to claim a prominent
      position in the management of patients with essential hypertension in the future.

PMID- 8861550
TI  - Stavudine: a review of its pharmacodynamic and pharmacokinetic properties and
      clinical potential in HIV infection.
AB  - Stavudine is a nucleoside analogue which undergoes intracellular phosphorylation
      to its active metabolite, stavudine-5'-triphosphate. At clinically relevant
      concentrations, the active metabolite restricts HIV replication by inhibiting the
      inclusion of thymidine-5'-triphosphate into proviral DNA by HIV reverse
      transcriptase, and/or by causing DNA chain termination. Viral resistance to
      stavudine does not commonly develop during treatment. Where it has developed, up
      to a 12-fold increase in resistance has been observed in clinical isolates from
      patients treated with stavudine for long periods. Stavudine 40mg twice daily and
      zidovudine 200mg 3 times daily were compared in 822 patients at various stages of
      HIV infection who had previously received long term zidovudine therapy. Stavudine
      was superior for both primary and surrogate end-points including clinical
      progression, treatment failure, increase in CD4+ cell counts and bodyweight gain.
      In a larger study, stavudine 40mg twice daily provided greater benefit than
      stavudine 20mg twice daily in terms of weight gain, haematological findings and
      the number of hospitalisations in 11 784 patients intolerant of or resistant to,
      zidovudine and didanosine. Peripheral neuropathy is the major dose-limiting
      adverse event associated with stavudine therapy and occurred more frequently with
      stavudine than zidovudine. However, haematological adverse events were observed
      less frequently with stavudine than with zidovudine. Thus, stavudine is effective
      in alleviating signs and symptoms of HIV infection in patients intolerant of or
      no longer responding to, zidovudine or didanosine. It is also more effective than
      zidovudine in slowing disease progression in patients previously treated with
      zidovudine for long periods. The results of studies which will reveal the role of
      stavudine therapy in untreated patients and in combination with other anti-HIV
      agents are awaited with interest.

PMID- 8861567
TI  - Setting priorities in the Spanish health care system.
AB  - Increasingly sophisticated and expensive medical technologies, chronic illness
      and aging, and a population that insists upon the best health care and coverage,
      together demand that priorities be set in the public funding of health care. This
      article describes Spanish initiatives in dealing with such problems and analyses
      the ethical implications of health care legislation and rationing.

PMID- 8861569
TI  - Towards a two tier health system in the Netherlands: how to put theory into
      practice.
AB  - The Dutch health care system is developing a two, or multiple, tier system. How
      can moral principles be of help in assessing whether this is the right track?
      Instead of dismissing as unhelpful the principles that have been suggested so far
      and exchanging them for other, usually more complex, principles, it is suggested
      that the methods of moral inquiry be reconsidered.

PMID- 8861570
TI  - "Socialized medicine," resource allocation and two-tiered health care--the Danish
      experience.
AB  - This paper describes the present resource allocation problems in the Danish tax
      based public health care system and presents an analysis of the two policy
      options put forward as a solution to these problems: (1) explicit rationing of
      services, and (2) the introduction of two-tiered health care. It is argued that a
      two-tiered system with a private second tier is unlikely to be acceptable and
      viable in Denmark, whereas an introduction of a second tier within the public
      system may be more acceptable. It is further argued that present implicit
      rationing methods may be unethical and ought to be replaced by explicit
      rationing.

PMID- 8861571
TI  - The Norwegian welfare state in transition: rationing and plurality of values as
      ethical challenges for the health care system.
AB  - This paper presents the Norwegian national health care system and the manner in
      which the problems of rationing and pluralism of values create new ethical and
      political challenges. The paper concludes with some doubts about the feasibility
      of the transformation taking place within this kind of health care system, with
      special reference to governmental control and consumer preferences.

PMID- 8861551
TI  - Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid
      organ transplant rejection.
AB  - The murine monoclonal antibody muromonab CD3 (OKT3) is directed against the CD3
      antigen on peripheral human T cells and effectively blocks all T cell function.
      Prophylaxis with muromonab CD3 (5mg intravenously once daily for 10 to 14 days)
      as induction therapy together with corticosteroids, azathioprine and delayed
      cyclosporin (sequential therapy) optimises early graft function by delaying the
      potentially nephrotoxic and hepatotoxic effects of cyclosporin until graft
      function is established. Although clinical data are limited (by inconsistencies
      in trial design and trial size), prophylactic muromonab CD3-based sequential
      therapy is significantly more effective than standard triple therapy in the
      prophylaxis of allograft rejection in renal and hepatic, but not cardiac,
      transplant recipients. Benefits are particularly notable in patients with delayed
      graft function. No significant between-treatment differences in patient survival
      have been observed. The overall efficacy of muromonab CD3- and polyclonal-based
      prophylactic regimens appears to be similar, although results vary between
      investigators and confirmation is needed. An anti-interleukin-2 monoclonal
      antibody-based prophylactic regimen improved graft and patient survival compared
      with muromonab CD3-based prophylaxis in hepatic transplant recipients.
      Antimuromonab CD3 antibodies may develop; however, muromonab CD3 may be
      successfully reused in patients with low titres. Preliminary pharmacoeconomic
      data suggest that mean drug costs are greater with quadruple immunosuppressive
      regimens containing muromonab CD3, antithymocyte globulin (ATG) or antilymphocyte
      globulin (ALG) than with triple therapy. Drug costs with prophylactic muromonab
      CD3-based regimens were similar or greater than those with polyclonal-based
      protocols. The first doses of muromonab CD3 are associated with the 'cytokine
      release syndrome'. More severe first-dose events include aseptic meningitis,
      intragraft thromboses, seizures and potentially fatal pulmonary oedema. The
      incidence and/or severity of cytomegalovirus infection with prophylactic
      muromonab CD3 based immunosuppression is similar to or greater than that with
      triple therapy and ATG- or ALG-based regimens. However, the risk of infection and
      also the observed increase in lymphoproliferative disorders appears to be related
      to the degree of immunosuppression rather than to the drug itself Thus,
      sequential muromonab CD3-based therapy is more effective than standard triple
      therapy (in renal and hepatic transplant recipients) and appears to be similar to
      that of polyclonal-based regimens in the prophylaxis of transplant rejection.
      Although the routine use of prophylactic muromonab CD3 in low-risk patients with
      primary graft function does not appear to be justified, prophylactic muromonab
      CD3-based therapy has a role in patients at high risk of rejection.

PMID- 8861572
TI  - Free choice of sickness funds: economic implications and ethical aspects of the
      1992 health care reform in Germany.
AB  - To properly comply with the Health Sector Act of 1992 a functioning competition
      should be introduced in the interests of the insured of the German Statutory
      Health Insurance, while still maintaining the principle of solidarity. This is a
      critical order-political aim, because the principles of solidarity and self
      responsibility as typically understood are functionally in contradiction. This
      paper analyzes the important measures of the Organizational Reform and concludes,
      that the principle of self-responsibility ought to obtain priority. Therefore,
      the German legislature ought to focus on further competitively oriented reform
      steps.

PMID- 8861573
TI  - Enterprise association or civil association? The UK national health service.
AB  - This paper falls into three parts. In the first part I will briefly review the
      current process of reform that the United Kingdom National Health Service is
      undergoing. Two fundamental motivations for reform, the desire for increased
      efficiency and for an increased responsiveness to patients' needs and preferences
      will be discussed in greater detail. The second part attempts to provide a
      perspective on the moral debate concerning health care reform by introducing the
      distinction between 'civil association' and 'enterprise association' as proposed
      by the political philosopher Michael Oakeshott. In the final part, this
      distinction will be used to analyze the moral and political constitution of the
      National Health Service, in order to establish the relevance and scope of
      concerns with efficiency and patient and public accountability. A framework
      within which the current reforms can be assessed is thereby outlined.

PMID- 8861574
TI  - Augmented meniscal healing with free synovial autografts: an organ culture model.
AB  - We examined whether or not free synovial autografts can augment the healing of
      lesions artificially created in the human knee meniscus in an organ culture
      model. The effectiveness of free synovial autografts was also compared with that
      of fibrin glue (Tisseel). In the control group, the accumulation of cellular
      components increased at the edge of a 4-mm meniscal defect following culture,
      although no cells were found to invade the defect. In the fibrin glue group, an
      increased migration of cells into fibrin glue packed into the defect was observed
      until 4 weeks following cultivation. However, newly formed collagen produced by
      the cells in the fibrin glue was minimal even 4 weeks after cultivation. In
      contrast, in the synovial group, newly formed collagen production, as well as
      cellular proliferation, increased in the grafted synovium with time after
      cultivation. By 4 weeks, the gap between the edge of the defect and the grafted
      synovium was bridged by newly formed collagen tissue, indicating improved
      histologic repair. Our results suggest that free autogenous synovial tissue
      grafts in meniscal lesions are superior to fibrin glue, and that interpositional
      synovial autografts to augment repair of meniscal tears in the avascular zone may
      be clinically useful.

PMID- 8861575
TI  - Long-term results of transtrochanteric rotational osteotomy for femoral head
      osteonecrosis.
AB  - Twenty transtrochanteric rotational osteotomies were performed in 19 patients
      with osteonecrosis of the femoral head (average age 32 years; range 19-55 years).
      There were 17 hips at Ficat stage III and three at stage IV. The average head
      rotation achieved was 70 degrees (range 55 degrees-95 degrees) Fourteen hips were
      converted to a total hip arthroplasty after an average period of 5.6 years (range
      1.5-12.7 years). Five hips have maintained a good clinical result and normal
      function for an average period of 11.3 years (range 9.2-13.5 years). One patient
      with an ankylosed hip was lost to follow-up at 3.5 years. All hips with
      incomplete rotation of the necrotic fragment out of the weight-bearing area were
      revised to total hip arthroplasties. All unrevised hips had radiographic evidence
      of mild to moderate osteoarthritis. Total hip arthroplasty was deferred for a
      modest period in most patients, and conversion was performed without difficulty.
      However, we no longer advocate transtrochanteric rotational osteotomy because of
      unpredictable results and technical difficulties, especially with large lesions.

PMID- 8861576
TI  - Does vacuum-mixing improve the fatigue properties of high-viscosity poly(methyl
      methacrylate) (PMMA) bone cement? Comparison between two different evacuation
      methods.
AB  - The objective was to verify different reports in the literature which show an
      increase of stability using vacuum-mixing of bone cement, by testing the fatigue
      properties of bone-cement specimens (Palacos R). Evacuation of the poly(methyl
      methacrylate) (PMMA) and evacuation with additional pressurization (Draenert
      system) were used to manufacture the specimens. Although we found improvement in
      the ultimate bending strength for evacuated Palacos R, an increase of fatigue
      stability could not be found either for vacuum-mixed cement or for vacuum-mixed
      and compressed cement. As fatigue failure is one of the most important factors
      leading to aseptic loosening of cemented alloarthroplasties, we conclude that the
      long-term results cannot be improved by vacuum-mixing this cement.

PMID- 8861577
TI  - Standardized ultrasound examination for evaluation of instability of the
      acromioclavicular joint.
AB  - Anteroposterior X-ray views of both acromioclavicular (AC) joints with 10-kg
      weights held in each hand are the generally accepted procedure for diagnosis of
      Tossy I-III grades of AC joint separation. An analogous diagnosis can be made by
      standardized ultrasound examination. Ten individuals with Tossy-I, 11 with Tossy
      II and 8 with Tossy-III instability were examined both radiographically and by B
      mode ultrasound. The degree of AC joint separation was uniformly determined on
      the basis of a calculated index (AC Index = AC joint width of uninjured side/AC
      joint width of injured side). The mean AC Index for Tossy-I instability
      determined by ultrasound was 1.0; mean indices of 0.49 and 0.5 were determined
      for Tossy-II injury by ultrasound and X-ray, respectively, and of 0.21 and 0.2,
      respectively, for Tossy-III instability. Statistical analysis showed significant
      differences between the mean AC indices of all three groups (P < 0.0001). We
      conclude that the reliability of ultrasound examination of AC joint instability
      is equal to that of radiographic measurement. Standard X-rays of the shoulder
      remain mandatory only to exclude fracture. The indication for operative
      stabilization of the AC joint can be established on the basis of the grade of AC
      joint instability measured by the side-effect-free and cost-effective method of
      ultrasound examination (AC Index < 0.3 equivalent to Tossy-III instability).

PMID- 8861578
TI  - Induced healing of aneurysmal bone cysts by demineralized bone particles. A
      report of two cases.
AB  - Two cases of induced healing of aneurysmal bone cyst (ABC) following
      intralesional implantation of a bone paste made of autogeneic bone marrow and
      allogeneic bone powder are reported. The calcaneum in one case and the superior
      pubic ramus in the other were blown out by an ABC and would have required
      extensive surgery. Via a minimal exposure, the cyst was partially evacuated and
      filled with an admixture of a partially demineralized bone particles with bone
      marrow. Ossification of the peripheral shell was the first sign of healing and
      was observed within the first 3 postoperative months. Successful healing was
      observed in both cases. The rationale underlying this intralesional treatment was
      that the bone grafting material might reverse ABC expansion by promoting
      ossification through a bone induction mechanism. The concept of this treatment
      was to retain the ABC tissue, using its own intrinsic osteogenic potential to
      promote healing. By triggering intralesional new bone formation, the bone paste
      represented an effective means to reverse the expanding phase of ABC. The
      particulated bone allograft was easy to handle and to introduced in an irregular
      cavity. Moreover, as a complete cyst evacuation was not required, a minimal
      surgical approach could be used so that the risks and morbidity associated with
      an extensive approach were reduced. Its use is of particular interest in poorly
      accessible areas like the pelvis and spine.

PMID- 8861579
TI  - Role of internal and external fixation in ankle fusion.
AB  - Between August 1980 and September 1993, 35 tibiotalar arthrodeses in 34 patients
      with primary and secondary osteoarthritis of the ankle were performed. Two
      different surgical techniques were employed. Internal screw fixation according to
      Wagner and Pock [20] and an external fixation method according to the resection
      compression arthrodesis by Charnley and Muller [14]. Twenty patients with 21
      fusions could be investigated retrospectively. For evaluation we used self
      assessment, clinical examination and radiographic analysis in combination with
      the score described by McGuire et al. [12]. In 80% the results were good and
      satisfactory with a median improvement of 23 score points on a scale of 100% 95
      points, respectively. The most important advantages were pain relief and increase
      of walking distance. The fusion rate was 95%. We found osteoarthritis in the
      neighbouring joints did not have any influence on the surgical result. With
      respect to the two surgical techniques, the internal screw fixation method
      achieved fusion earlier with fewer complications and better improvement according
      to the McGuire score. Tibiotalar fusion is a safe therapy with reproducible good
      results involving pain relief, full weight-bearing and increase of walking
      distance.

PMID- 8861580
TI  - Is instillation drainage for the treatment of infected joints, bones and soft
      tissues still up to date?
AB  - For the treatment of infected joints, bones and soft tissues, either an
      instillation drainage therapy or the use of gentamicin-polymethyl-methacrylate
      (PMMA) chains (Septopal) in addition to surgical revision and systemically given
      antibiotics is currently in clinical use. We investigated 102 patients treated in
      our clinic by means of instillation drainage and compared the results with those
      obtained with gentamicin-PMMA chains by other authors. The overall long-term
      success with non-recurrence of the infection is nearly comparable (80%
      instillation drainage, 84% gentamicin-PMMA chains); however, with instillation
      drainage the duration of hospitalisation is significantly longer (mean 42.26 days
      vs 15.3 - 33 days). Additionally, there was a high rate of germ shifts with
      instillation drainage (33.3%) and a disappointing result in 20 infected
      endoprostheses (9 recurrences with 11 revisions). Regarding the intensive nursing
      care required and the necessary isolation from other patients, instillation
      drainage can only be recommended for the therapy of infected joints, bones and
      soft tissues if the results are better in comparison with gentamicin-PMMA chains.
      An improvement may be achieved with the closed instillation drainage system.

PMID- 8861581
TI  - Advantage of the transprosthetic drainage system (TDS) for application in
      cemented hip arthroplasty--a standardized experimental comparison with other
      cementing techniques.
AB  - We constructed a computer-assisted implantation device to compare different
      cementing techniques of stem implantation in total hip arthroplasty, thus
      avoiding any manual influence during implantation. We used an intramedullary plug
      in each case. Conventional cementing techniques, employing an additional lateral
      drain for the femoral canal or applying the cement by hand, did not lead to a
      satisfyingly reproducible quality of the cement mantle. With the vacuum cementing
      technique, in which an additional cannulated screw is inserted into the plug from
      the lateral side of the femur for the application of the vacuum, the cement
      mantle improved in quality, but there was still a relatively high number of
      bubbles incorporated in the cement. We think that, even under improved
      experimental circumstances, it is not always possible to place the cannulated
      screw correctly into the plug in order to achieve a satisfying drainage of the
      femoral canal with this procedure. The transprosthetic drainage system showed the
      best results due to the optimized position and working capacity of the drain.

PMID- 8861582
TI  - Ulnar shortening osteotomy in posttraumatic ulnar impaction syndrome.
AB  - Twenty-eight patients (average age 45 years) with posttraumatic ulnar impaction
      syndrome underwent ulnar shortening osteotomy of 3-15 mm. Contributing factors
      were malunited fractures of the distal radius in 20, diaphyseal fractures of the
      ulna and radius in 6, resection of the radial head and a traumatic tear of the
      triangular fibrocartilage in 1 patient each. Evaluation at an average follow-up
      of 20 months showed a high rate of satisfied patients (89%), but according to
      Chun's modification of the Gartland-Werley score there were 1 excellent (3.5%),
      11 good (39.5%), 11 fair (39.5%) and 5 poor (17.5%) results. Degenerative changes
      of the distal radioulnar joint were associated with fair and poor results, and
      ulnar shortening osteotomy is only recommended in ulnocarpal impaction with an
      intact distal radioulnar joint. Osteotomy fixation with 3.5 mm dynamic
      compression plates enabled immediate postoperative mobilisation and resulted in a
      low complication rate. There was no advantage for the technically more demanding
      oblique as compared with a transverse osteotomy.

PMID- 8861583
TI  - Knee joint proprioception in normal volunteers and patients with anterior
      cruciate ligament tears, taking special account of the effect of a knee bandage.
AB  - Proprioception of the knee joint was tested in 30 healthy volunteers with
      clinically inconspicuous knee joints. To examine proprioception, an angle
      reproduction test was performed. We could not document any differences between
      the left and the right knee joint or between men and women. At the mid-range,
      proprioception was worse compared with the end range of motion. In addition, 25
      patients with an isolated rupture of the anterior cruciate ligament were
      evaluated, 14 before and 11 after operative anterior cruciate ligament (ACL)
      reconstruction. Preoperatively, there was a significant deterioration of
      proprioception compared with the control group. We were able to show a positive
      influence of a knee bandage on the proprioception of the injured knee. Patients
      after ACL reconstruction showed no significantly better proprioception compared
      with the preoperative group.

PMID- 8861584
TI  - The ceramic cup type Lindenhof. Results 10-14 years after implantation.
AB  - We followed up 10-14 years postoperatively the 106 ceramic cups type 'Lindenhof'
      that were implanted in the years 1978-1982. In that time, only 7 (6.6%) cups had
      to be changed due to aseptic loosening. Examination of 73 (68.9%) cups showed
      that only 4% of the patients were dissatisfied. Using the score of Merle
      d'Aubigne, we found 89% good and very good results. The high number of cup
      migrations reported by other authors could not be verified: we saw 35% in all.
      Most of them appeared in the early postoperative period, stabilized themselves
      and were not accompanied by pain. Our 10-year survival rate for this ceramic cup
      is 92%, including the septic changing of arthroplasties.

PMID- 8861585
TI  - Clinical and radiological results after Austin bunionectomy for treatment of
      hallux valgus.
AB  - The results of the Austin osteotomies for hallux valgus deformity performed at
      the Orthopedic Hospital Gersthof were reviewed at least 1 year after surgery. Of
      the 53 consecutive patients (66 operations) with an average follow-up of 24.3
      months, 49 patients (62 feet) were interviewed. Of the reviewed patients 86.6%
      achieved good or excellent clinical results. The complication rate was 8%,
      including hallux varus n (3), superficial n (1) and deep n (1) wound infections,
      hypoaesthesia n (2), and reflex sympathetic dystrophy n (1). There was one case
      of avascular necrosis of the first metatarsal head and none of non-union. The
      Austin osteotomy is a safe and effective treatment of mild and moderate hallux
      valgus deformity.

PMID- 8861586
TI  - The morphological effects of synthetic augmentation in posterior cruciate
      ligament reconstruction: an experimental study in a sheep model.
AB  - The treatment of posterior cruciate ligament (PCL) injuries remains
      controversial. Due to various problems, PCL reconstruction has not consistently
      produced the knee stability desired. Biological graft tissue undergoes a
      remarkable healing process comprising different phases. The strength of
      autogenous graft material decreases soon after operation. During this early
      healing phase synthetic augmentation could protect the graft tissue from
      overloading or overstretching, supporting the tissue revitalization and
      remodeling process. In order to evaluate the morphological effects of the
      ligament augmentation device (LAD) on a free patellar tendon autograft in PCL
      reconstruction, a comparative study in sheep was conducted. In 24 mature sheep,
      the PCL was replaced with either a patellar tendon autograft alone or a patellar
      tendon autograft augmented by the LAD. The LAD was fixed at both ends. After the
      operation the animals were not immobilized. Tibial fixation was released 8 weeks
      postoperation. The autografts of both groups were histologically evaluated after
      2, 6, 16, 26, 52, and 104 weeks. In addition to necrotic and degenerative
      alterations, a remarkable inflammatory reaction could be seen in the LAD
      augmented autografts early postoperation. Compared with the nonaugmented
      autografts, tissue formation and remodeling were delayed in the augmented group.
      After 1 and 2 years, the morphology of the autograft tissue was similar in both
      the augmented and nonaugmented group and differed from that of a normal PCL. The
      LAD was surrounded by a chronic inflammatory reaction, and collagen fiber
      ingrowth into the LAD was not observed. Using transmission electron microscopy,
      small diameter collagen fibrils were predominant in the graft tissue of both
      groups. Thus, a better remodeling of the autograft tissue in the presence of the
      LAD could not be demonstrated in this particular study. The value of synthetic
      augmentation of biological grafts in PCL reconstruction seems to be questionable
      at present.

PMID- 8861587
TI  - Arthroscopically assisted arthrodesis of the ankle joint.
AB  - In 26 patients we performed an arthroscopically assisted arthrodesis of the
      ankle. The patients' ages ranged from 31 to 69 years. The male:female ratio.
      Sixteen patients had posttraumatic degenerative joint disease, three patients
      suffered from a previous infection, four patients had rheumatoid arthritis, and
      three patients had an osteochondritis dissecans in their past history. The time
      taken for surgery ranged from 65 to 135 min. Compared with open procedures we
      documented less postoperative swelling and minor use of analgesics. Time of
      follow-up was a minimum of 6 months and a maximum of 75 months. In 22 patients we
      found solid fusion at the time of followup. Fusion was accomplished by 2 months
      postoperatively in four patients, by 3 months in nine patients, by 4 months in
      another six patients, and by 6 months in 3 patients. Three patients did not
      evidence any bony fusion, but they were free of pain. In one patient an open
      revision was necessary. According to our experience, we recommend
      arthroscopically assisted arthrodesis of the ankle in patients with degenerative
      joint disease without rotational or varus/valgus malalignment, severe bone
      defects or neuropathic disease.

PMID- 8861588
TI  - Follow-up (6-9 years) results of the uncemented CLS Spotorno stem.
AB  - The aseptic loosening rate in uncemented hip endoprostheses, especially the stem,
      is one of the most discussed problems among hip surgeons within the last few
      years. The first generation of uncemented stems had an essentially higher
      loosening rate compared with cemented stems. Although there are many reasons for
      this disappointing fact, the type of primary fixation and polyethylene wear are
      the two main ones. We reviewed 145 sequential uncemented CLS Spotorno stems,
      which achieved their primary fixation and bony in- or ongrowth predominantly in
      the metaphyseal region. The mean age of the patients was 54.9 years (range 37-76
      years), and average follow-up was 7.8 years. The evaluation included both
      clinical (Merle d'Aubigne and Harris Hip Score) and radiographic parameters
      (plain X-rays). The medium-term follow-up showed a survival rate of 96.7% and
      good functional score results in more than 90%. Special attention was paid to the
      so-called thigh pain phenomenon which, despite current views, was found to be
      unexpectedly low (only one case). Although these results are encouraging, a
      further long-term follow-up of more than 10 years will have to show whether or
      not comparable results to cemented stems can be realised.

PMID- 8861589
TI  - Clinical symptoms caused by intra-articular fibrous plicae after knee
      replacement. Arthroscopic diagnosis and therapy.
AB  - In 29 patients with persistent complaints after knee replacement we found intra
      articular fibrous tissue in different areas of the joint. In 26 patients
      diagnostic arthroscopy was followed by arthroscopic resection of the tissue. The
      fibrous tissue was differentiated into five types. Type 1 represented a
      transverse fibrous band located at the superior margin of the femoral component
      of the prosthesis. A type 2 plica was a lateral plica extending from the
      superolateral border of the patella to the infrapatellar fat pad. The type 3
      fibrous band reached from the inferior pole of the patella to the intercondylar
      area. The type 4 nodulus was located at the superior border of the patella, and
      the type 5 plica was a meniscoid-like tissue between the femoral and the tibial
      component. Arthroscopic resection resolved the symptoms in 25 of the patients.
      Different factors seem to contribute to the development of intra-articular plicae
      after knee alloarthroplasty.

PMID- 8861590
TI  - Age-related magnetic resonance imaging morphology of the menisci in asymptomatic
      individuals.
AB  - In 82 asymptomatic subjects aged 8-62 years we evaluated the menisci by magnetic
      resonance imaging (MRI). Using a 1.0-tesla imager spin-echo sequences (SE
      700/20), partial-saturation sequences (500/10), and short-time inversion-recovery
      sequences (1600/130/30) were performed. For grading the degeneration of the
      meniscus, a standard classification (grades 0-4) was used. Positive MRI findings
      correlated with the patients' age. In SE sequences, a grade 0 meniscus was found
      in 45.5% of all cases, grade 1 in 33.2%, grade 2 in 16.1%, grade 3 in 4.5%, and
      grade 4 in 0.7%. In PS sequences, we found grade 0 in 23.9%, grade 1 in 27.5%,
      grade 2 in 31.5%, grade 3 in 15.9%, and grade 4 in 1.1%. In STIR sequences, we
      found grade 0 in 56%, grade 1 in 25.4%, grade 2 in 11.1%, grade 3 in 6%, and
      grade 4 in 1.6%. Correlation of meniscus degeneration with subjects' age showed
      an increase of grade 3 and 4 lesions with advancing age. Subjects older than 50
      years presented with grade 3 and 4 lesions in the SE sequence in 28.5% of the
      cases, in PS sequences in 40.7%, and in STIR sequences in 25%. In asymptomatic
      subjects, MRI shows an increasing prevalence of meniscal alterations which
      correlates with age. Especially in subjects older than 50 years, a significant
      number of meniscal tears must be expected. This shows the potential danger of the
      use of MRI alone as a basis for the determination of surgical intervention.

PMID- 8861591
TI  - Atrophy of the nuchal muscle and change in cervical curvature after expansive
      open-door laminoplasty.
AB  - We analyzed computed tomography (CT) images and plain X-ray films of 53 patients
      who had undergone expansive open-door laminoplasty, in a 3-year study. The
      relationship between the postoperative changes in the nuchal muscles and those in
      the cervical curvature was investigated. On postoperative CT images, the cross
      sectional area of all nuchal muscles was reduced to approximately 80% of its
      preoperative size. This atrophic change was especially intense in the multifidus
      muscle and the semispinalis cervicis muscle. Postoperative cross-sectional area
      of the deep nuchal muscles was reduced approximately 30% from its preoperative
      size. No significant correlation was found between the all cross-sectional area
      of the nuchal muscles and the cervical curvature. However, a weak correlation was
      found between the deep nuchal muscles area and the curve index (correlation
      coefficient 0.29).

PMID- 8861592
TI  - Revascularisation of bone allografts following vascular bundle implantation: an
      experimental study in rats.
AB  - Revascularisation and cellular repopulation of fresh and cryopreserved allografts
      was observed following implantation of a vascular bundle in an experimental study
      in rats. Fresh and cryopreserved rat allografts were harvested from Lewis rats
      and implanted into Spraque-Dawley rats. The femoral vascular bundle was implanted
      into 2-cm segments of allograft placed in the medial aspect of the thigh of the
      recipient rats. Non-vascularised controls were used for comparison. Histological
      studies indicated the revascularisation pattern. Cryopreserved allografts with
      vascular bundle implantation showed early neovascularisation from the endosteal
      surface, 20% of the necrotic lacunae was repopulated with living cells at the end
      of 24 weeks. Fresh allografts with vascular implantation were rejected by the
      host immune mechanisms and showed early breakdown and fragmentation. Cellular
      repopulation was not observed in the non-vascularized allografts. Secondary
      vascularization following a vascular bundle implantation may enhance the
      biological properties of an allograft and therefore has significant potential
      clinical applications.

PMID- 8861593
TI  - Spinous process-plasty following lumbar laminectomy as a contributing factor to
      spine stability.
AB  - A 10-year retrospective study of 41 consecutive patients who underwent "spinous
      process-plasty" is presented. We carried out laminectomy of the lumbar spine in
      cases of spinal stenosis, dorsomedial herniated disc and recurrent disc
      herniation with firm scars (traumatic and tumour cases are not included). To
      forestall the development of laminectomy's negative effects on spine stability,
      we initiated the spinous processes' reconstruction. Two groups of patients who
      underwent laminectomy form the basis of this presentation, one group with
      "spinous process-plasty" (41 patients) and the other (11 patients) without it. On
      postoperative neutral and dynamic X-ray films we paid attention to horizontal
      displacements larger than 3 mm and to negative intervertebral angular
      displacement. Considering such criteria, only 3.8% of those with "spinous process
      plasty" developed a radiographic instability in contrast to 25% of patients
      without "spinous process-plasty". These results support the use of this
      technique, which provides postlaminectomy lumbar spine stability.

PMID- 8861594
TI  - Solitary eosinophilic granuloma of the pelvis in children. A report of three
      cases.
AB  - We present three cases of eosinophilic granuloma of the ilium in children.
      Imaging investigations (computed tomography and magnetic resonance imaging) did
      not elucidate the disease but rather revealed patterns more like malignant
      tumours than a benign condition. However, these investigations were of value in
      directing the surgeon to the correct site for biopsy.

PMID- 8861595
TI  - Corrective osteotomy for malunion of the distal radius: the effect of concomitant
      ulnar shortening osteotomy.
AB  - Positive ulnar variance due to inadequate correction of radial length is a common
      disorder after radial corrective osteotomy. To avoid this complication we
      performed a combination of ulnar-shortening osteotomy and radial corrective
      osteotomy in 6 of 22 radial corrections. The indication for the combined
      procedure was a relative ulnar length of minimally 6 mm. The functional outcome
      was fair in 1 and good in 5 cases with combined osteotomy. Overall, the
      functional results were good in 17 cases, and pain in the distal radioulnar joint
      was observed in 3 of 22 patients. Positive ulnar variance was the reason for pain
      in only 1 patient. Eventually, 2 hemiresections of the ulnar head (Bower's
      arthroplasty) were performed. It appears that a combination of ulnar shortening
      and radial osteotomy is a reliable technique, which can reduce symptoms and need
      for secondary operations on the ulnar side of the wrist.

PMID- 8861596
TI  - Muscle-pedicle grafts or muscle-pedicle-bone grafts in the treatment of avascular
      necrotic femoral heads.
AB  - The paper is a microangiographic study of the revascularisation of experimentally
      devascularised femoral heads in rabbits. We examined the revascularisation
      process in muscle pedicles implanted into the devascularised femoral heads. Two
      forms of pediculated grafts were used: muscle-pedicle grafts and muscle-bone
      pedicle grafts. The pedicles were formed from the gluteal muscle. The end of the
      muscle-bone-pedicle graft was formed by a small piece of trochanter major. The
      revascularisation process was quicker in the case of the pure muscle-pedicle
      grafts, and it was delayed in muscle-bone-pedicle grafts, which can be explained
      by the morphological differences between the two forms. A 2-week delay was
      observed during the 12-week observation period. A quicker process may mean better
      progress of revascularisation.

PMID- 8861597
TI  - Surgically treated acetabular fractures in adult patients.
AB  - In this retrospective study, 27 acetabular fractures treated by open reduction
      and internal fixation with an average follow-up of 3.7 years (1.5-4.0) are
      reported. Reduction leaving a displacement of < or = to 2 mm was achieved in 9
      hips (30%). Good or excellent results were obtained in 22 hips (82%), and in 2
      patients who were referred to us after 3 weeks, we performed supra-acetabular
      osteotomy to obtain congruent joints with fairly good results. The most common
      complication was heterotopic ossification in 59% of the patients, which led to
      poor results in 2 patients with grade IV. Avascular necrosis of the hip occurred
      in 2 patients, and 1 patient developed a late deep infection, which led to
      osteomyelitis and fused hip.

PMID- 8861598
TI  - Osteoarthrosis following the Putti-Platt operation.
AB  - The objective of this study was to search for any degenerative changes in the
      shoulder joint following the Putti-Platt operation in a long-term follow up
      study, as most papers regarding that operation report a redislocation rate and a
      limitation of external rotation, but only a few mention osteoarthrosis (OA).
      Patients operated on between 1945 and 1971 answered a questionnaire and were
      invited for a clinical examination including standard X-rays of the shoulder.
      These films were compared with those taken preoperatively. OA was classified
      according to the Samilson and Prieto grading. Twenty-six patients could be re
      examined on average 26 years after the operation. Fifteen had evident
      radiological signs of OA. According to Samilson and Prieto there were 11 mild, 2
      moderate and 2 severe cases of OA. Nine patients had a Hill-Sachs defect and 3, a
      Bankart lesion. Patients over the age of 25 years at the time of the first
      dislocation developed OA more often. Following the Putti-Platt operation one has
      to expect radiological signs of OA in a long-term follow-up. Mainly minor forms
      are seen. Older patient age at the time of the first dislocation is a
      predisposing factor for the development of OA.

PMID- 8861599
TI  - Iliacus pyomyositis mimicking septic arthritis of the hip joint.
AB  - The iliacus muscle is closely associated with the psoas muscle, femoral nerve,
      hip joint, pelvic and intraabdominal structures; thus, its disorders may present
      as lower abdominal pain, hip pain, or femoral neuropathy. Iliacus pyomyositis, a
      primary bacterial infection of the skeletal muscle not secondary to a contiguous
      skin, bone, or soft-tissue infection, presenting as hip pain, femoral neuropathy,
      and sympathetic effusion of the hip joint in an 8-year-old boy mimicked septic
      arthritis of the hip joint. Computed tomography was helpful in delineating the
      accurate location of the lesion. Surgical drainage and appropriate antibiotic
      therapy led to complete resolution and full functional recovery.

PMID- 8861600
TI  - Two cases of closed dislocation of the interphalangeal joint of the thumb.
AB  - Dorsal dislocation of the interphalangeal (IP) joint of the thumb is a rare
      injury, and closed dislocation without fracture is especially unusual. We present
      here two cases of closed dislocation of the thumb which were reduced by
      manipulation.

PMID- 8861601
TI  - Traumatic posterior dislocation of the shoulder with fracture of the acromion in
      a child.
AB  - Posterior dislocation of the shoulder is extremely rare in children. We
      encountered a posterior dislocation of the shoulder complicated by fracture of
      the acromion in a 14-year-old boy. He recovered uneventfully after immediate
      manual reduction performed under general anesthesia and truncal plaster cast
      fixation. Early diagnosis and treatment are considered to be especially important
      in managing this injury.

PMID- 8861602
TI  - Multiple benign schwannomas of the foot.
AB  - Benign schwannomas occur very rarely in the foot. We report a case of a 46-year
      old patient with multiple benign schwannomas of the foot. Eighteen schwannomas
      associated with the medial plantar nerve present for at least 1 year were
      excised, with preservation of the involved nerve and disappearance of the
      patient's symptoms. No signs of von Recklinghausen's disease were found.

PMID- 8861603
TI  - Morphology of identified corticospinal cells in the rat following motor cortex
      injury: absence of use-dependent change.
AB  - After unilateral injury to the forelimb area of the motor cortex, rats are
      reported to show relatively increased use of the ipsilateral forelimb during
      exploratory behavior and a concomitant transient increase in dendritic growth in
      neurons in the undamaged motor cortex. To identify the specific population of
      cells in motor cortex that undergo such use-dependent change, we examined the
      morphology of corticospinal pyramidal cells in the intact hemisphere 18 days
      following unilateral motor cortex damage. Corticospinal neurons in the motor
      cortex were retrogradely labeled with injections of the fluorescent tracer, DiO,
      into the cervical enlargement of the spinal cord. Seven days later, the rats
      received a lesion in the forelimb area of the contralateral motor cortex and 18
      days following the lesion, limb use was assessed in two behavioral tests after
      which the rats were sacrificed. Under fluorescent light, corticospinal cells were
      visualized and injected with a horseradish peroxidase-fluorescein conjugate that
      was then reacted with diaminobenzidine. The labeled cells were reconstructed and
      the number and centrifugal order of the branches were analyzed. The increased use
      of the paw contralateral to the intact motor cortex was not associated with an
      increase in dendritic arborization in corticospinal motor neurons in the intact
      motor cortex. The results are discussed in light of methodological and
      theoretical considerations relevant to the study of neural plasticity in the
      motor system.

PMID- 8861604
TI  - Long-latency responses of brain noradrenergic neurons to noxious stimuli are
      preferentially attenuated by intravenous morphine.
AB  - The nucleus locus coeruleus (LC) has been strongly implicated in the processing
      of noxious stimuli. Consistent with this, previous studies have shown that
      spontaneous LC discharge is depressed by morphine. However, effects of morphine
      on evoked responses of LC neurons to noxious stimuli have not been systematically
      examined. We reported recently that responses to footshock stimuli in rat locus
      coeruleus neurons consist of an early (A-fiber mediated) component and a
      previously undescribed late (C-fiber mediated) component. In the present study,
      we administered analgesic doses of morphine (0.1, 0.5, or 1.0 mg/kg, i.v.) to
      determine the effect on A- and C-fiber components of footshock responses in LC
      neurons. Doses of 0.5 and 1.0 mg/kg significantly attenuated the C-fiber mediated
      response of LC neurons without affecting the A-fiber response component.
      Spontaneous LC discharge was reduced by administration of all doses of morphine.
      Both depressive effects of morphine were abolished by intravenous administration
      of naloxone. In contrast, local microinfusion of naloxone into the LC abolished
      the morphine-induced decrease of spontaneous discharge but did not prevent the
      depression of the C-fiber mediated footshock response by morphine. This indicates
      that the site of action for morphine's attenuation of the late LC response to
      footshock stimulation is outside of the LC. The results are consistent with the
      hypothesis that the late (C-fiber-mediated) footshock responses in locus
      coeruleus are involved in the processing of noxious stimuli and may contribute to
      anti-nociceptive mechanisms.

PMID- 8861605
TI  - Alterations in brain protein kinase C after experimental brain injury.
AB  - Regional activities and levels of protein kinase C were measured after lateral
      fluid percussion brain injury in rats. At 5 min and 20 min after injury, neither
      cofactor-dependent nor -independent PKC activities in the cytosol and membrane
      fractions changed in the injured and contralateral cortices or in the ipsilateral
      hippocampus. Western blot analysis revealed decreases in the levels of cytosolic
      PKC alpha and PKC beta in the injured cortex after brain injury. In the same
      site, a significant increase in the levels of membrane PKC alpha and PKC beta was
      observed after injury. Although the level of PKC alpha did not change and that of
      PKC beta decreased in the cytosol of the ipsilateral hippocampus, these levels
      did not increase in the membrane fraction after injury. The levels of PKC gamma
      were generally unchanged in the cytosol and the membrane, except for its decrease
      in the cytosol of the hippocampus. There were no changes in the levels of any PKC
      isoform in either the cytosol or the membrane of the contralateral cortex after
      injury. The present results suggest a translocation of PKC alpha and PKC beta
      from the cytosol to the membrane in the injured cortex after brain injury. The
      observation that such a translocation occurs only in the brain regions that
      undergo substantial neuronal loss suggests that membrane PKC may play a role in
      neuronal damage after brain injury.

PMID- 8861606
TI  - Ethanol actions on the mechanisms of Ca2+ mobilization in rat hippocampal cells
      are mediated by protein kinase C.
AB  - The effects of ethanol on intracellular free Ca(2+) concentration, [Ca](i), were
      studied in cultured rat hippocampal neurons using fluo-3 and confocal microscopy.
      Ethanol application transiently elevAted [Ca](i) due to Ca(2+)-induced Ca(2+)
      release from internal stores since the effect was observed also in solutions
      containing zero Ca(2+) or 0.3 mM La(3+) and restoration of external Ca(2+)
      content led to secondary response in presence of ethanol. The sites of highest
      [Ca]i increases correlated well with those obtained after Ca(2+) release from
      caffeine-and IP3-sensitive internal stores. After single ethanol exposure the
      caffeine-evoked [Ca](i) transients were potentiated whereas Ca(2+) release
      induced by IP(3)-mobilizing agonists was suppressed. Similar effects were
      observed by activation of protein kinase C (PKC) by phorbol esters which also
      occluded ethanol actions. Ethanol increased fluorescence of Rim-1, a PKC
      indicator dye. The data obtained are consistent with ethanol activation of PKC
      whereby Ca(2+) release via ryanodine receptors is potentiated and IP(3) receptors
      are down-modulated. Since the effects of both ethanol and phorbol esters were
      mimicked by cytochalasins B and D, PKC-induced cytoskeleton phosphorylation and
      its subsequent rearrangements can be responsible for observed effects.

PMID- 8861607
TI  - Halothane affects both inhibitory and excitatory synaptic transmission at a
      single identified molluscan synapse, in vivo and in vitro.
AB  - In the isolated CNS of Lymnaea, a peptidergic neuron termed VD4 makes
      monosynaptic connections with identified pedal A cluster neurons. In this study,
      the pedal A (PeA) neurons were further divided into two subgroups depending upon
      whether they received an inhibitory or excitatory input from VD4. PeA cells
      inhibited by VD4 were designated PeA(I), whereas those excited by VD4 were termed
      PeA(E). Both inhibitory and excitatory effects of VD4 stimulation on the PeA(I)
      and PeA(E) cells, respectively, were mimicked by exogenous FMRFamide in culture
      (in vitro), implicating this or a related peptide as the transmitter utilized at
      the VD4-to-PeA synapses. We tested the ability of the general anesthetic,
      halothane, to affect either the inhibitory or the excitatory peptidergic synapses
      between VD4 and the PeA neurons, both in the isolated CNS (in vivo) and at the in
      vitro reconstructed synapses. In the presence of 1% halothane, the excitatory
      synaptic potential between VD4 and the PeA(E) cells was either depressed or
      completely abolished, whereas the inhibitory synaptic potential between VD4 and
      the PeA(I) cells was unaffected in the presence of 1% halothane. The inhibitory
      potential between VD4 and the PeA(I) cells was, however, blocked in 2% halothane.
      In order to determine halothane' 5 site of action, exogenous FMRFamide was
      applied to both PeA(E) and PeA(I) cells in the presence of 1 or 2% halothane. In
      1% halothane, the excitatory responses produced by FMRFamide were substantially
      reduced or abolished, whereas the inhibitory responses to FMRFamide were
      maintained and enhanced in duration in 1% halothane. In 2% halothane, the
      inhibitory responses to exogenous FMRFamide remained unchanged. It, therefore,
      appears that halothane exerts effects at both the pre- and postsynaptic level of
      the synapse, although presynaptic transmitter release is probably not
      substantially affected until a concentration of 2% halothane is reached. Our data
      provide the first evidence that clinically relevant concentrations of halothane
      (1-2%) affect both excitatory and inhibitory peptidergic synaptic transmission
      between identified neurons in the nervous system. Furthermore, excitatory
      transmission is abolished at lower anesthetic concentrations than inhibitory
      transmission.

PMID- 8861608
TI  - Differences in the expression of GABA(A) receptors between functionally
      innervated and non-innervated granule neurons in neonatal rat cerebellar
      cultures.
AB  - We had earlier found that granule neurons in cultures of small explants of
      neonatal rat cerebellar cortex could be placed in two groups: cells in one group
      showed spontaneous synaptic activity and also had a large response to
      applications of 1 microM gamma-aminobutyric acid (GABA) while cells in the other
      lacked spontaneous activity and also showed much lower sensitivity to GABA [25].
      For convenience, the more responsive cells will be termed A-type neurons, while
      the less responsive cells will be termed B-type. We have undertaken a comparison
      of the responses mediated by activation of GABA A receptors for the two types of
      neurons. A-type neurons have a larger maximal response to GABA (about 10 times
      that for B-type neurons), suggesting that they express more functional GABA(A)
      receptors. The concentration of GABA producing half-maximal activation of A-type
      neurons is somewhat less (12 mu M) than that for B-type neurons (41 microM),
      while the Hill coefficients are similar. Responses of both types of cell
      desensitize to prolonged applications of GABA. At a given concentration of GABA
      the responses of A-type neurons desensitize more rapidly than the responses of B
      type neurons, indicating that the physiological properties of the receptors
      differ. Responses of A-type neurons are also potentiated to a significantly
      lesser extent by either chlordiazepoxide or alphaxalone than are the responses of
      B-type neurons, indicating that the pharmacological properties of the receptors
      differ. These data indicate that A-type and B-type granule neurons in our
      cultures express GABA(A) receptors which differ in number, physiological
      properties and pharmacological responsiveness. We have also confirmed the
      observation that almost all A-type neurons also show spontaneous synaptic
      currents, while almost no B-type neurons do.

PMID- 8861609
TI  - Comparison of cerebrospinal fluid monoamine metabolite levels in dominant
      aggressive and non-aggressive dogs.
AB  - Aggression has been shown to be related to reduced serotonergic activity in
      humans and non-human primates, and in rodents. We now studied the relationship
      between cerebrospinal fluid (CSF) monoamine metabolites and canine aggression in
      21 dominant-aggressive dogs (Canis familiaris) and 19 controls. The diagnosis of
      dominance-related aggression was based upon a history of biting family members in
      contexts associated with dominance challenges. Post-mortem CSF 5-HIAA, MHPG and
      HVA were measured by high-performance liquid chromatography using electrochemical
      detection. Concentrations of CSF 5-HIAA (P = 0.01) and HVA (P < 0.001) were lower
      in the aggressive group (median values: 5-HIAA 202.0 pmol/ml; HVA 318.0 pmol/ml)
      than in controls (5-HIAA 298.0 pmol/ml; HVA 552.0 pmol/ml). No differences were
      noted in CSF MHPG levels. Differences in 5-HIAA were maintained after controlling
      for breed and age of dogs, but HVA differences may have been breed-dependent.
      Lower levels of 5-HIAA (P = 0.02) and HVA (P = 0.04) were found in the subgroup
      of aggressive dogs with a history of biting without warning (5-HIAA 196.0
      pmol/ml; HVA 302.0 pmol/ml) compared to dogs that warned (5-HIAA 244.0 pmol/ml;
      HVA 400.0 pmol/ml). This study suggests that reduced serotonergic function is
      associated with aggressive behavior and impaired impulse control in dogs, a
      finding that is consistent with observations in primates, and suggests that
      serotonin modulates aggressive behavior throughout mammals.

PMID- 8861610
TI  - Heterotrimeric G protein activation rapidly inhibits outgrowth of optic axons
      from adult and embryonic mouse, and goldfish retinal explants.
AB  - Axons in the adult mammalian CNS normally do not regenerate following axotomy
      even though they retain the capacity for growth under certain experimental
      conditions. Although this implies that the regeneration of adult axons is under
      regulative control, very little is known about the signaling pathways
      "responsible" for this regulation. This study examines the possibility that a G
      protein signaling system exists in adult mouse optic fibers and that it functions
      to regulate axonal outgrowth. To induce the growth of optic fibers, retinas from
      adult mouse were placed in organotypic culture under serum free conditions and
      allowed to regenerate onto a laminin substrate. Heterotrimeric G proteins were
      stimulated by adding mastoparan (MST) to the medium while monitoring growing
      fibers with time lapse microscopy. Mastoparan treatment produced rapid growth
      cone collapse and axonal retraction which persisted while MST was present. Prior
      addition of pertussis toxin (PTX), which irreversibly inactivates the G proteins,
      G(o) and G (i),completely blocked the effect of MST, confirming that MST was
      acting through the PTX sensitive G proteins. Selective activation of G proteins
      in the growth cone by local application of MST with a micropipet was equally
      effective. For comparison, equivalent experiments were performed on embryonic day
      15 retinal explants and on retinal explants from adult goldfish, which normally
      regenerate in vivo. MST similarly inhibited these axons and this effect was
      blocked by PTX. However, embryonic fibers were less reliably affected compared to
      goldfish or adult mouse, suggesting a developmentally regulated sensitivity. The
      presence of G-proteins in the mouse axons was further tested
      immunohistochemically using antibodies against G(o)/G(i). Positive staining was
      detected in the growth cones and shaft of adult and embryonic mouse optic fibers.
      These findings demonstrate that G protein activation inhibits axonal outgrowth
      and suggest that there may be a G protein signaling pathway that normally
      regulates this outgrowth. However, since this pathway appears to exist in both
      axons that can regenerate and those that normally do not, the presence of PTX
      sensitive G proteins alone cannot account for regenerative failure. Regenerative
      failure may instead be explained as the selective or increased activation of this
      pathway in the adult mammalian CNS.

PMID- 8861611
TI  - Interaction of nociceptive and non-nociceptive cutaneous afferents from foot sole
      in common reflex pathways to tibialis anterior motoneurones in humans.
AB  - In six healthy subjects, the reflex responses of the tibialis anterior muscle
      (TA) to stimulation of the cutaneous afferents arising from plantar foot, were
      studied at rest and during different levels of steady voluntary contraction of
      the TA. At rest, the threshold of the response and the threshold of subjective
      pain sensation coincided. The mean latency of this TA nociceptive response was
      84.7 ms. Steady voluntary contractions of the TA, which was increased
      progressively from 3% to 15% of the maximum voluntary contraction, produced a
      significant and parallel reduction in the threshold and latency of the response:
      at 15%, the mean latency was about 26 ms shorter than at rest and its threshold
      was about half (i.e. below the pain threshold). The conduction velocity of the
      afferents responsible for TA response at rest was within the range of A-delta
      pain afferents (mean 27.4 m/s), whereas during voluntary contraction it was
      within the A-beta fibre range (mean 45.1 m/s). This suggests that descending
      command makes the discharge of low-threshold, fast-conducting fibres sufficient
      for reflex activation of TA motoneurones (MNs). Central delay (about 4 ms) and MN
      recruitment order (according to the size principle) were found to be the same for
      both nociceptive and non-nociceptive TA reflex responses. Finally, experiments of
      spatial summation revealed an interaction between nociceptive and non-nociceptive
      inputs at a premotoneuronal level. It is therefore proposed that nociceptive and
      non-nociceptive cutaneous afferents arising from the foot sole use the same short
      latency spinal pathway to contact TA MNs and that their relative contribution to
      its segmental activation is contingent upon descending command.

PMID- 8861612
TI  - Endogenous Alzheimer's brain factor and oxidized glutathione inhibit antagonist
      binding to the muscarinic receptor.
AB  - An endogenous inhibitor (< 3,500 Da) of antagonist binding to the muscarinic
      acetylcholine receptor has been extracted from Alzheimer's disease (AD) brain
      with trifluoracetic acid. Oxidized glutathione, (GSSG) has also been found to
      inhibit antagonist binding to the receptor. However, in its reduced form,
      glutathione (GSH) like other reducing agents, markedly enhances the inhibitory
      effect of both GSSG and the endogenous AD inhibitor. EDTA and the free radical
      scavengers Mn(2+) and Trolox, a vitamin E analog, block the action of the
      endogenous AD inhibitor but not of GSSG in the presence of GSH. Further, while
      GSSG inhibition is reversible, the action of the endogenous AD inhibitor is
      irreversible, consistent with a free radical mechanism. The enhancement of
      endogenous AD inhibitor activity by GSH suggested that GSH may be involved in
      formation of the free radical generated by the inhibitor. The glutathione thiyl
      radical is shown to inhibit antagonist binding to the receptor and is, therefore,
      a good candidate for the free radical formed by the endogenous AD inhibitor. The
      ability of Trolox to block the reduction in muscarinic receptor binding caused by
      the endogenous AD inhibitor is encouraging and suggests that free radical
      scavengers, such as vitamin E, may have a potential therapeutic role in AD by
      protecting the integrity of the muscarinic receptor.

PMID- 8861613
TI  - Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss
      in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.
AB  - Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal
      dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve
      release of DA in presynaptic DA terminals, which is associated with increased
      formation of oxygen-based free radicals. We have recently shown that METH-induced
      striatal DA depletion is attenuated in transgenic (Tg) mice that express the
      human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically
      address the issue of loss of DA terminals. In the present study, we have used
      receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to
      evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg
      as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH
      caused decreases in striatal DA uptake sites in a dose-dependent fashion. The
      loss of DA terminals was more prominent in the lateral region than in the medial
      subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by
      METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice
      showing the greatest protection. Female mice were somewhat more resistant than
      male mice against these deleterious effects of METH. These results provide
      further evidence for a role of superoxide radicals in the long-term effects of
      METH. They also suggest the notion of a gender-specific handling of oxidative
      stress.

PMID- 8861614
TI  - Anteroventral third ventricle lesions attenuate pressor responses to serotonin in
      anesthetized rats.
AB  - When administered intravenously, serotonin (5-hydroxytryptamine; 5-HT) evokes a
      triphasic blood pressure response, consisting of the Bezold-Jarisch-associated
      depressor response, a pressor action, and long-lasting depressor response.
      Because the pressor response may, in part, be caused by central nervous system
      (CNS) activation by 5-HT, we predicted that destruction of the anteroventral
      third ventricle (AV3V) region, an area rich in 5-HT receptors, would attenuate
      increases in blood pressure to intravenous 5-HT. In anesthetized sham-lesioned
      and AV3V-lesioned Sprague-Dawley rats, we measured mean arterial pressure (MAP),
      heart rate (HR), and lumbar sympathetic nerve activity (SNA) to increasing bolus
      doses of intravenous 5-HT (1, 2.5, 5, 10, 25 mu g/kg), before and after blockade
      of bradycardia using methylatropine (200 mu g/kg). In all rats, bolus injections
      of 5-HT elicited bradycardia accompanied by a fall in lumbar SNA and an initial
      hypotension followed by a pressor response and a longer lasting hypotensive
      response. The bradycardia, reduction in lumbar SNA, and both depressor responses
      were equivalent in sham-lesioned and AV3V-lesioned groups. Importantly, AV3V
      lesions attenuated pressor responses to increasing doses of 5-HT (3 +/- 1, 6 +/-
      4, 6 +/- 4, 17 -/+ 4 35 +/- 3 mmHg) compared to sham-lesioned controls (6 +/- 3,
      16 +/- 7, 33 +/- 5, 54 +/- 4, 51 +/- 6 mmHg; P < 0.0001). This attenuation was
      conserved following blockade of bradycardia with methylatropine (P < 0.01). In
      summary, pressor responses to intravenous 5-HT are diminished by AV3V lesions.
      These data indicate that the pressor component of the blood pressure response to
      intravenous 5-HT is partly dependent upon interaction with the CNS.

PMID- 8861615
TI  - Neuronal plasticity in aging: a quantitative immunohistochemical study of GAP-43
      distribution in discrete regions of the rat brain.
AB  - Age-related changes in neuroplasticity have been investigated considering the
      neuronal growth-associated protein GAP-43 as a marker of nerve cell structural
      adaptive capabilities. We carried out a quantitative immunohistochemical study on
      the distribution of GAP-43 in the molecular layer of the cerebellar cortex, in
      the inner molecular layer of the hippocampal dentate gyrus, in the stratum
      radiatum of the CA1 region, in layer 1 of the cingulate cortex and in the nerve
      fiber layer of the main olfactory bulb of 3-, 18- and 31-month-old Wistar rats. A
      decrease of GAP-43 immunoreactivity was observed in the old rats in comparison
      with the adult animals in all the 5 areas analyzed, although these variations
      were only statistically significant in the dentate gyrus, cingulate cortex and
      olfactory bulb. In these latter zones, GAP-43 immunolabeling is reduced by 54, 42
      and 38%, respectively, in the old versus the adult group. Comparing these data
      with the age-dependent decrease of neuron density innervating the areas
      investigated, we support the hypothesis that the decline of GAP-43 observed in
      old animals documents a consistent reduction of axon plasticity in the inner
      molecular layer of the dentate gyrus and in layer 1 of the cingulate cortex.
      These results suggest an important role of GAP-43 as a marker of age-dependent
      deterioration of synaptic plasticity, especially in those areas of the brain
      involved in memory and emotional behavior.

PMID- 8861616
TI  - Effects of Alzene and tacrine on water maze reference and working memory function
      in medial septal-lesioned rats.
AB  - The present study investigated the effects of repeated daily administration of a
      mixture containing free fatty acids (alpha-linolenic/linoleic acid in a 1:4 ratio
      at 25 mg/kg i.p., Alzene) on medial septal (MS) lesion-induced impairment of
      water maze (WM) spatial reference and working memory or passive avoidance (PA)
      behavior in adult rats (250-275 g at the beginning of the study). Alzene
      treatment was started 7 days before initiation of behavioral testing (WM
      reference memory testing on treatment days: 7-9 and 28-30 + passive avoidance on
      treatment days 31-32; WM working memory testing on treatment days: 7-10 and 38-31
      + passive avoidance testing on treatment days 32-33) and continued until the end
      of the study. Alzene improved WM reference memory (treatment days 7-9 and 28-30)
      and PA behavior (treatment days 31-32) as effectively as an anti-cholinesterase
      drug, tacrine 3 mg/kg (i.p.). However, in a separate group of MS-lesioned rats we
      observed that working memory (treatment days 7-10 and 28-31) was not improved by
      either Alzene or tacrine treatment. The present results suggest that Alzene
      treatment improves spatial reference memory and inhibitory avoidance in MS
      lesioned rats.

PMID- 8861617
TI  - Soleus H-reflex depression induced by ballistic voluntary arm movement in human.
AB  - A biomechanical and neurophysiological analysis of anticipatory postural
      adjustments associated with the early phase of a voluntary arm movement was
      carried out in normal human subjects. Arm elevation, performed at maximal
      velocity, was studied with unilateral arm movement in freely and counterbalanced
      (suspended in a safety harness) standing humans. The ground reaction force of
      both legs, tangential acceleration of the shank and electromyographic activity
      (EMG) of the anterior deltoid (AD), biceps femoris (BF) and soleus (Sol) muscles
      were recorded. Sol H-reflexes of both legs were also elicited. To examine how the
      Ia inhibitory and presynaptic inhibitory pathways are related to anticipatory
      postural adjustments, additional Sol H-reflexes were elicited using the classical
      conditioning-test technique (time interval 2 and 15 ms, respectively). In this
      study, we systematically described biomechanical and EMG phenomena that precede
      and follow the onset of voluntary arm movements. Prior to and during the arm
      movement (i.e. AD activation), a sequence of EMG modifications occurred in
      ipsilateral BF and Sol muscles. Those modifications preceding BF activation
      included silent phases in Sol EMG and depression of Sol H-reflexes. By comparing
      EMG modifications with depressions of the Sol H-reflex, we conclude that Ia and
      presynaptic inhibitory pathways do not play a specific role in those Sol H-reflex
      depressions. Moreover, because Sol H-reflex depression occurs in both freely
      standing and counterbalanced postures, anticipatory postural adjustment appear to
      be preprogrammed in the central nervous systems unrelated to peripheral neural
      mechanisms. Since changes of EMG activities of ipsilateral BF and Sol appeared
      simultaneously and Sol H-reflex depressions were dependent on EMG activities of
      ipsilateral BF, control commands to anticipatory postural adjustment would excite
      BF and inhibit Sol.

PMID- 8861618
TI  - Localisation of NADPH diaphorase activity and NOS immunoreactivity in astroglia
      in normal adult rat brain.
AB  - This study demonstrates the co-localisation of NADPH diaphorase activity and GFAP
      immunoreactivity in non-neuronal cells in weakly fixed brain sections from normal
      adult rats. The presence of GFAP immunoreactivity in these cells indicates that
      they are astroglia. In addition, cells possessing the morphological
      characteristics of astroglia were weakly immunoreactive for the endothelial
      isoform of nitric oxide synthase (eNOS)--these cells also co-localised NADPH
      diaphorase activity. Furthermore, cells immunoreactive for eNOS displayed GFAP
      immunoreactive processes. This cytochemical evidence strongly suggests that
      resting astroglia are potential sources of nitric oxide--a powerful modulator of
      cell activity.

PMID- 8861619
TI  - Interactions between excitotoxins and the Na+/K+-ATPase inhibitor ouabain in
      causing neuronal lesions in the rat hippocampus.
AB  - A possible indirect role of glutamate in causing the neuronal death found after
      intracerebral administration of a low dose of ouabain (0.1 nmol) has been
      evaluated. This dose of ouabain produces a more extensive neuronal lesion than
      those caused by glutamate receptor agonists (kainate at an equimolar dose, or
      NMDA (N-methyl-D-aspartate) at a 50-fold higher dose). The selective glutamate
      receptor antagonists, dizocilpine (MK-801) and NBQX (2,3-dihydroxy-6-nitro-7
      sulfamoyl-benzo(F)quinoxaline), in doses which blocked the direct toxicity of
      glutamate receptor agonists acting on either the NMDA and non-NMDA classes of
      glutamate receptor, failed to provide more than a minor protection against
      ouabain-induced neuronal death in the rat dorsal hippocampus. In contrast, the
      non-selective glutamate receptor antagonist, kynurenate (100 nmol) reduced the
      damage by around 70%. The difference in neuroprotection found between the
      glutamate receptor antagonists suggests that kynurenate may protect by a non
      glutamatergic mechanism. Co-administration of ouabain and glutamate receptor
      agonists (kainate, NMDA or glutamate) resulted in additive rather than
      synergistic damage to hippocampal neurons. The results suggest that in vivo,
      ouabain and excitotoxins probably cause neuronal death by independent mechanisms.

PMID- 8861620
TI  - Innate differences in medial septal area burst firing neurons and the hippocampal
      theta rhythm during ambulation in selectively bred rat lines.
AB  - Previous studies have demonstrated a higher mean peak frequency of the
      hippocampal (HPC) theta rhythm during REM sleep in alcohol-nonpreferring (NP)
      rats when compared with alcohol-preferring (P) rats. Burst firing neurons of the
      medial septal area (MS/VDB) are thought to pace the HPC theta rhythm during REM
      sleep and ambulation. Therefore, extracellular action potentials of MS/VDB burst
      firing neurons and HPC-CA1 field potentials were recorded simultaneously in
      ambulating P and NP rats. These recordings revealed that the mean peak frequency
      of the HPC theta rhythm during ambulation was higher in NP rats (7.62 +/- 0.12
      Hz) as compared with P rats (7.21 +/- 0.14 Hz) (P < 0.05). Consistent with the
      difference in the HPC theta rhythm, the burst pattern of MS/VDB neurons exhibited
      a shorter inter-burst interval in the NP rats (NP 82.4 +/- 5.4 ms, P 97.4 +/- 8 1
      ms P < 0.05). The difference in the inter-burst interval was confirmed by the
      distribution of inter-spike intervals in cumulative inter-spike interval
      histograms and the frequency of peaks in the mean cumulative autocorrelation
      histograms for P and NP rats. The mean cumulative autocorrelation histograms for
      P and NP rats also revealed that the regularity of the burst pattern in NP rats
      was sustained over a longer time period as determined by the decay constant. The
      cross-correlation of MS/VDB burst activity and the HPC theta rhythm showed a
      strong relationship between the two signals in P and NP rats. In both P and NP
      rats, two similar phase relationships were observed between MS/VDB bursting
      neurons and the HPC theta rhythm. These findings are in agreement with the
      hypothesis that MS/VDB burst firing neurons are responsible for the variation in
      the HPC theta rhythm between the two lines. Other mechanisms consistent with
      these findings are also discussed.

PMID- 8861621
TI  - Characterization of U-101017 as a GABA(A) receptor ligand of dual functionality.
AB  - Drugs acting on the benzodiazepine site of GABA(A) receptors are much safer than
      barbiturates, but are still liable to abuse. Recently, we have reported that a
      benzodiazepine site agonist, U-97775 (a dihydroimidazoquinoxaline analog), may
      have minimal abuse liability because of its interaction with a second, low
      affinity site on GABA(A) receptors, the occupancy of which, at high drug
      concentrations, leads to a reversal of its agonistic activity on the
      benzodiazepine site and inhibition of GABA-induced Cl- currents [Br. J.
      Pharmacol. 115 (1995)19-24]. Here we report that U-101017 (7-chloro-5[(cis-3,5
      dimethylpiperazine)carbonyl]imidazo[1,5a]quinoline- 3-carboxylate) is another
      similar benzodiazepine site agonist possessing the ability to reverse its
      agonistic activity at higher concentrations, but its ability to inhibit GABA
      currents is considerably milder than that of U-97775. In the alpha 6 beta 2 gamma
      2 subtype where these drugs have no agonistic activity, for instance, U-101017 at
      concentrations up to 80 mu M, showed no appreciable effect on GABA currents,
      whereas U-97775 inhibited the currents with an IC(50) value of 10 mu M as
      measured with the whole cell patch clamp techniques in human embryonic kidney
      cells expressing recombinant receptors. Similar, milder inhibition of GABA
      currents by U-101017 was observed in the alpha 1 beta 2 gamma 2 and alpha 3 beta
      2 gamma 2 subtypes. Furthermore, U-101017 was of higher efficacy in the alpha 1
      beta 2 gamma 2 than alpha 3 beta 2 gamma 2 subtypes as compared to diazepam,
      although its binding affinity was not appreciably different in the two subtypes.
      We conclude that U-101017 is a partial benzodiazepine agonist, somewhat selective
      to the alpha 1 beta 2 gamma 2 subtype, and with the ability to limit its own
      agonistic activity over a wide range of doses through its interaction with the
      low affinity site, but without potential convulsant activity, inherent to agents
      which block GABA currents.

PMID- 8861622
TI  - The induction of homo- vs. heterosynaptic LTD in area CA1 of hippocampal slices
      from adult rats.
AB  - The induction of long-term depression (LTD) was investigated in area CA1 of
      hippocampal slices from adult rats. To produce LTD, prolonged low-frequency
      stimulation (LFS, 900 stimuli at 1 Hz) was delivered to one of two independent
      Schaffer-collateral/commissural projections, while the second input served as a
      control to monitor heterosynaptic effects. The depression was calculated as
      percent decrease in the slope of the dendritic field EPSP relative to baseline
      values, and LTD was considered established if the response decrement was at least
      15% in magnitude and stable for 30-60 min. By delivering LFS in conditions of
      different relative baseline response magnitudes, it was revealed that the
      intensity of afferent low-frequency activity has a significant impact on the
      induction frequency, magnitude and input-specificity of the depression: the rate
      of LTD occurrence and the effect of LFS on the absolute response decrement
      increased successively as the stimulation strength was raised, but the impact of
      LFS on the relative LTD magnitude decreased at higher stimulation intensities;
      the depression was specific to the stimulated input (homosynaptic LTD) when
      baseline responses were spike-free, but spread to the pathway which was silent
      during LFS (heterosynaptic LTD) in experiments conducted above spiking threshold.
      The results indicate that in the adult rat (i) the induction of input-specific
      LTD is dependent on the level of synaptic activation during LFS, and (ii) LTD can
      easily be obtained in strongly stimulated pathways but may be the result of a
      generalized decrease in the postsynaptic response.

PMID- 8861623
TI  - Transient decrease of acetylcholinesterase in ventral horn neurons caudal to a
      low thoracic spinal cord hemisection in the adult rat.
AB  - Light microscopic enzyme histochemistry was employed to study the alterations of
      acetylcholinesterase (AChE) within lumbosacral ventral horn neurons at survival
      times of 1, 4, 7, 14, 28, 60, and 90 days after low thoracic spinal cord
      hemisection in adult rats. The intensity of histochemical staining was quantified
      using densitometric techniques. Virtually all ventral horn neurons of sham
      operated and unoperated animals, which served as controls, displayed intense AChE
      staining. Hemisection of the spinal cord induced a transient ipsilateral decrease
      of AChE staining in most neuronal cell bodies and in the neuropil of lamina IX at
      all segmental levels caudal to the lesion. Quantitative analysis of
      representative segments revealed a reduction of AChE in the ventral horn during a
      postoperative (p.o.) period of 1 to 28 days followed by a phase of recovery over
      the next two months. AChE activity still remained slightly reduced, even at 90
      days p.o. The transient decrease in AChE is a well-known metabolic response of
      axotomized motoneurons. However, the observed changes of AChE reactivity in
      intact motoneurons ipsilateral and caudal to the hemisection are presumably
      induced by the interruption of supraspinal descending pathways. These metabolic
      changes may functionally affect the whole motor unit and be involved in the
      disturbances of motor function following spinal cord injury.

PMID- 8861624
TI  - Effect of intraventricular injections of dihydro-beta-erythroidine (DH beta E) on
      spatial memory in the rat.
AB  - The analysis of the behavioral effect of the nicotinic acetylcholine receptor
      (nAChR) antagonists has been generally based on drugs which act at the associated
      ion channel. In contrast dihydro-beta-erythroidine (DH beta E) is a competitive
      antagonist at the nAChR. Using rats, DH beta E was injected intraventricularly
      prior to training in two spatial tests, the Morris Water Maze and a Win-Stay
      radial maze. In addition DH beta E 300 nmol was used to reverse the effect of (-)
      nicotine on locomotor activity. In the Morris Water Maze DH beta E (300 nmol)
      disrupted memory of the platform location as measured by crosses of the area in a
      probe trial. At 300 nmol DH beta E showed no sensorimotor effects in a visible
      platform test. In the Win-Stay task there was a significant, dose dependent
      disruption of spatial memory. A dissociation of nicotine's effects on locomotor
      activity was observed, in that DH beta E 300 nmol was able to significantly
      attenuate (-)-nicotine enhancement of horizontal motor activity, but did not
      affect the initial reduction of vertical activity. Nicotinic processing of memory
      appears to be involved in these tests of spatial memory.

PMID- 8861625
TI  - Niflumic acid-induced increase in potassium currents in frog motor nerve
      terminals: effects on transmitter release.
AB  - The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied
      on frog neuromuscular preparations by conventional electrophysiological
      techniques. Niflumic acid reduced the amplitude and increased the latency of
      endplate potentials in a concentration-dependent manner. Neuromuscular junctions
      pretreated with niflumic acid (0.05-0.5 mM) showed much less depression than
      control when they were stimulated with trains of impulses. Inhibition of
      acetylcholine release was reverted by raising the extracellular Ca(2+)
      concentration but not by simply washing out the preparations with niflumic acid
      free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal
      antiinflammatory drug, did not affect the niflumic acid-induced inhibition of
      evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of
      miniature endplate potentials and had a dual action on the frequency of
      miniatures: it decreased their frequency at 0.1 mM whereas it produced an
      enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid
      (0.1 - 1 mM) reversibly increased the amplitude and affected the kinetics of
      presynaptic voltage-activated K+ current and Ca(2+)-activated K(+) current in a
      concentration-dependent manner. Niflumic acid (0.1 - 1 mM) irreversibly decreased
      the amplitude and reversibly affected the kinetics of the nodal Na(+) current.
      Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion,
      niflumic acid reduces acetylcholine release by increasing presynaptic K+
      currents. This may shorten the depolarizing phase of the presynaptic action
      potential and may reduce the entry of Ca(2+) with each impulse.

PMID- 8861626
TI  - Changes in movement-related brain activity during transient deafferentation: a
      neuromagnetic study.
AB  - Neuromagnetic fields from the left cerebral hemisphere of three healthy, right
      handed subjects were investigated preceding and during voluntary index finger
      movements performed every 8-15 s under two different experimental conditions:
      before (stage A) and during (stage B) anesthetic block of median and radial
      nerves at the wrist. The anesthesia caused blocking of cutaneous receptors and
      some of the proprioreceptors from a wide hand area, including the entire index
      finger. However, the index finger movements were not impaired because the muscles
      participating in the task were not anesthetized. The magnetic signals of the
      brain sources corresponding to the main components of the movement-related
      neuromagnetic fields (motor field, MF and movement-evoked field I, MEFI) were
      mapped and localized using a moving dipole model. In the three investigated
      subjects the MF and MEFI dipole sources were stronger (30% on average) during
      stage B than during stage A. No significant changes in spatial coordinates of the
      estimated dipole locations between stages A and B were observed. This was true
      for both MF and MEFI. The results show that the MEFI reflects not only
      proprioceptive input from the periphery but cutaneous inputs as well. In this way
      the results support the view that cutaneous inputs play a specific role in the
      cortical control of movement.

PMID- 8861627
TI  - Effects of omega-conotoxin MVIIC on veratridine-induced cytotoxicity and
      cytosolic Ca(2+) oscillations.
AB  - External Ca(2+) entry through various Ca(2+)-channel subtypes is responsible for
      the large oscillations of the cytosolic Ca(2+) concentrations, [Ca(2+)](i), and
      cell death induced by veratridine in primary cultures of bovine chromaffin cells.
      Blockade by omega-conotoxin GVIA (GVIA) of N-type Ca(2+) channels, by omega
      agatoxin IVA (IVA) of P-type Ca(2+) channels, or by furnidipine of L-type Ca(2+)
      channels did not afford cytoprotection. However, (omega-conotoxin MVIIC (MVIIC),
      a wide-spectrum blocker of N-, P- and Q-type Ca(2+) channels greatly protected
      the cells against the cytotoxic effects of veratridine. Furnidipine further
      enhanced the cytoprotecting effects of MVIIC. MVIIC but not furuidipine, markedly
      reduced the oscillations of [Ca(2+)](i) induced by veratridine in single fura-2
      loaded chromaffin cells. The results suggest that Ca(2+) entry through any of the
      different Ca(2+) channel subtypes present in bovine chromaffin cells might be
      cytotoxic. They also support two ideas: (i) that wide-spectrum neuronal Ca(2+)
      channel blockers (i.e. MVIIC) might be better cytoprotecting agents than more
      specific neuronal Ca(2+) channel blockers (i.e., GVIA, IVA, furnidipine); and
      (ii) that combined Ca(2+) channel blockers may provide greater cytoprotection
      than single compounds.

PMID- 8861628
TI  - Hypoxic pretreatment protects against neuronal damage of the rat hippocampus
      induced by severe hypoxia.
AB  - The present study investigates whether under conditions of successive hypoxic
      exposures pretreatment with mild (15% O(2)) or moderate (10% O(2)) hypoxia,
      protects hippocampal neurones against damage induced by severe (3% O(2)) hypoxia.
      The ultrastructural findings were also correlated with regional superoxide
      dismutase (SOD) activity changes. In unpretreated rats severe hypoxia induced
      ultrastructural changes consistent with the aspects of delayed neuronal death
      (DND). However, in preexposed animals hippocampal damage was attenuated in an
      inversely proportional way with the severity of the hypoxic pretreatment. The
      ultrastructural hypoxic tolerance findings were also closely related to increased
      regional SOD activity levels. Thus the activation of the endogenous antioxidant
      defense by hypoxic preconditioning, protects against hippocampal damage induced
      by severe hypoxia. The eventual contribution of increased endogenous adenosine
      and/or reduced excitotoxicity to induce hypoxic tolerance is discussed.

PMID- 8861629
TI  - Endoplasmic reticulum is missing in dendritic spines of Purkinje cells of the
      ataxic mutant rat.
AB  - Dilute-opisthotonus (dop) is a spontaneous ataxic mutation in the rat, regulated
      by an autosomal recessive gene. Immunohistochemical staining with anti-inositol
      1,4,5-trisphosphate receptor antibody and electron microscopic examinations
      revealed that the endoplasmic reticulum in dendritic spines of Purkinje cell was
      missing in the ataxic rat. This could impair the intracellular signal
      transduction in the parallel fiber-Purkinje cell synapse, and be a cause of the
      severe ataxic movement.

PMID- 8861630
TI  - Increased preproenkephalin mRNA and preprotachykinin mRNA in the striatum of
      Rolling mouse Nagoya.
AB  - Although Rolling mouse Nagoya (RMN) has been considered to demonstrate cerebellar
      dysfunction, our previous metabolic and electrophysiological studies also
      revealed a dysfunction of the basal ganglia, with the presumable primary site of
      dysfunction being the striatum. In the present study, we investigated the
      neurochemical functions of the striatum. In RMN, both preproenkephalin mRNA and
      preprotachykinin mRNA increased significantly in the striatum, with unaltered GAD
      mRNA, [(3)H]spiperone binding, [(3)H]QNB binding and preprosomatostatin mRNA,
      thus indicating the dysfunction of striatal projection neurons. These findings
      support the hypothesis that the site of primary dysfunction in the basal ganglia
      is in the striatum of RMN.

PMID- 8861631
TI  - Serum factor from diabetic patients with or without retinopathy stimulates
      superoxide anion production by normal polymorphonuclear leukocytes.
AB  - Oxygen free radicals (OFRs) have been implicated in the pathogenesis of diabetic
      microangiopathy. The effects of serum from insulin-dependent diabetes mellitus
      patients with or without retinopathy on the production of superoxide anion by
      normal polymorphonuclear leukocytes (PMNs) were measured spectrophotometrically
      and compared with that of age matched controls. Superoxide anion production by
      PMNs incubated with serum from retinopathy-free patients or patients with
      retinopathy was significantly higher than that of controls (P=0.0002 and 0.0001,
      respectively). Furthermore, superoxide anion production by PMNs incubated with
      serum from patients with retinopathy was significantly higher than retinopathy
      free patients (P=0.02). These observations suggest that a diabetic serum factor
      provoked a significant generation of superoxide anion in normal PMNs, a
      phenomenon found parallel to the presence of retinopathy, indicating that OFRs
      may play a role in the progression of diabetic retinopathy. The nature of this
      serum factor remains to be clarified.

PMID- 8861632
TI  - A computer and video display based system for training eccentric viewing in
      macular degeneration with an absolute central scotoma.
AB  - A new approach designed to establish the most suitable area for eccentric viewing
      and to teach and train patients with severe age-related macular degeneration
      (AMD) to use the eccentric viewing technique is described. Using a computer and
      video display based system, as well as software written specifically for this
      purpose, we investigated and trained ten consecutive patients with AMD. The
      patients were 80.1 + or - 5.6 years old, on average. All of them had an absolute
      central scotoma. Mean visual acuity was 0.035 + or - 0.016. After 30 min of
      testing, instruction and reading on the screen, followed by 2.6 + or - 0.69 one
      hour training sessions, on average, with the low vision therapist, reading
      newspaper and book texts with the aid of hyperoculars or aplanatic systems and a
      very short reading distance, the patients achieved a reading speed of 58.9 + or -
      19.7 words/min, significantly (p<0.001) higher than the initial speed when
      reading on the screen, 11.5 + or - 4.5 words/min.

PMID- 8861633
TI  - Extracapsular cataract extraction in diabetic eyes. The role of YAG laser
      capsulotomy.
AB  - Cataract surgery may exacerbate preexisting diabetic retinopathy. Especially
      diabetics with active retinal neovascularisation are at high risk of rubeosis
      iridis after intracapsular cataract extraction. Thirty-five eyes previously
      treated with panretinal photocoagulation underwent extracapsular cataract
      extraction with posterior chamber lens implantation. Twenty-eight eyes with
      retinal neovascularisation required further Argon laser PRP after surgery.
      Fourteen eyes required YAG-laser capsulotomy. From the group of eyes without YAG
      laser capsulotomy none developed neovascular glaucoma. From the YAG laser
      capsulotomy group six eyes developed rubeosis iridis and neovascular glaucoma.
      Our results indicate that eyes in which PRP has been performed, have an excellent
      prognosis after ECCE with posterior chamber lens implantation only if YAG Laser
      posterior capsulotomy is not performed.

PMID- 8861634
TI  - Surgical treatment of large corneal dermoid.
AB  - Corneal and limbal dermoids are uncommon choristomatous corneal tumors. They
      clinically present as round or oval, whitish or yellowish cones protruding on the
      anterior surface of the eyeball. They are composed of ectodermal (keratinized
      epithelium, hairs, sebaceous and sudoriferous glands, nerves, smooth muscles and,
      less frequently, teeth) and mesodermal elements (fibrous tissue, fat, blood
      vessels and cartilage) combined in different proportion. If fat dominates in
      histology of the tumor, it is called a lipodermoid. A case of a two-year old boy
      with a large corneal dermoid on the right eye is presented. Dermoid covered
      almost the whole cornea and was associated with adherence of the atrophic iris to
      the posterior corneal surface and partial congenital cataract. Surgical therapy
      included excision of dermoid together with the superficial lamellae of the
      corneal stroma and penetrating keratoplasty. Satisfactory tectonic and esthetic
      outcome was achieved and has been maintained for four postoperative years now.

PMID- 8861635
TI  - Neuronal ceroid lipofuscinosis in the Polish Owczarek Nizinny (PON) dog. A
      retinal study.
AB  - Visual dysfunction and neurological symptoms were found in Polish Owczarek
      Nizinny (PON) dogs. Two dogs were examined, one at 2 years of age and the other
      one at 4 years. The oldest dog was totally blind. The 2-year-old dog developed
      mental disturbances and the 4-year-old dog became severely ataxic.
      Ophthalmoscopical findings were retinal hyper-reflectivity, attenuation of the
      retinal vessels and the presence of greyish to brown spots in the fundus.
      Electrophysiological and ultrastructural studies were performed in the 2-year-old
      dog. Scotopic ERG responses were absent, whereas 30 Hz cone flicker responses
      were recordable, although with an amplitude reduced to about 30% of the normal
      level. A slow negative potential replaced the c-wave, indicating a dysfunction of
      the RPE. Intracellular inclusions with a granular appearance or containing
      membranous fingerprint-like or curvilinear profiles, resembling ceroid, were
      found in different retinal cells. The RPE cells in the central areas were charged
      with autofluorescent material having similar structure, Photoreceptor
      degeneration was most severe in the central areas, corresponding to the RPE
      changes. It appears than the PON dog may provide a new animal model for neuronal
      ceroid lipofuscinosis.

PMID- 8861636
TI  - Influence of topical cyclosporine A and dissolvent on corneal epithelium
      permeability of fluorescein.
AB  - The corneal stroma is the major barrier to penetration for the lipophilic
      Cyclosporine A (CsA) molecule and prevents the use of the common ophthalmic
      solvents. At present, corn oil, castor oil and olive oil are the three most
      commonly used vehicles. The aim of this study was to determine the effect that
      topically applied CsA dissolved in different oils has on corneal epithelial
      permeability measured by fluorophotometry. Forty healthy volunteers, with absence
      of ocular or systemic disease and not receiving topical or systemic drugs were
      enrolled. Measurements were taken before and 45 min after the instillation of 40
      microliters of a 2% aqueous solution of sodium fluorescein without preservatives.
      Basal corneal permeability and the permeability 24 h after the instillation of 2%
      CsA-olive oil, olive oil alone, 2% CsA-castor oil, castor oil alone, 2% CsA-corn
      oil and corn oil alone, were calculated. To prepare the topical 2% CsA, a
      Sandimmun oral solution (Sandoz, Basel, Switzerland) was employed under sterile
      conditions. We found that epithelial permeability 24 h after the instillation of
      any CsA formulations or solvents increased more than 6.62 times (p <0.001). No
      differences in corneal permeability values were found between any of the CsA
      formulations and the vehicles. We conclude that oils used to dissolve CsA are
      mainly responsible for the increased corneal epithelial permeability. No
      differences were found in the effects of the tested solvents on corneal
      epithelial permeability.

PMID- 8861637
TI  - Nearwork-induced transient myopia: a critical review.
AB  - The literature on nearwork-induced transient myopia (NITM) is reviewed, with NITM
      being defined as the short-term myopic far point shift immediately following a
      sustained near visual task. A majority of these investigations demonstrated the
      presence of NITM for a variety of test parameters, e.g., visual acuity, contrast
      sensitivity and far point. Overall, these studies reported relatively small
      myopic shifts, with a mean of approximately 0.40 D and a range from 0.12 to 1.30
      D. The subsequent decay is characterized by an exponential function with a
      relatively short time course. While the precise etiology and implications of NITM
      remain unclear, speculations regarding its origin and relevance to clinical
      myopia are discussed. Studies that did not demonstrate NITM are also reviewed.

PMID- 8861638
TI  - Genetic differences between nitrate-negative and nitrate-positive C.
      pseudotuberculosis strains using restriction fragment length polymorphisms.
AB  - Corynebacterium pseudotuberculosis has been classified into two biotypes
      according to ability to breakdown nitrate (Biberstein et al., 1971). Restriction
      enzyme analysis (REA) has shown to reflect this differentiation, but numerous
      bands generated by this technique make interpretation difficult (Songer et al.,
      1988). Restriction fragment length polymorphism's (RFLP's) has become an accepted
      genetic tool and was used in this study to determine if differences in nitrate
      reduction and other phenotypic characteristics could be identified genetically.
      Thirteen C. pseudotuberculosis isolates from four species of domestic animals
      from different parts of the world were investigated for phenotypic and genetic
      differences. Three closely related bacteria, Corynebacterium ulcerans,
      Actinomyces pyogenes (previously C. pyogenes),and Rhodococcus equi (previously C.
      equi) were included in the study to determine if the RFLP bands were unique to C.
      pseudotuberculosis. All C. pseudotuberculosis isolates were positive for urease
      production. Some differences in maltose and sucrose fermentation ability and
      nitrate reduction were recorded. Genetic differences were identified between the
      nitrate-positive group and the nitrate-negative group using non-radioactive
      ribosomal RNA (rRNA) probes Southern blotted to restriction digests of ApaI,
      PstI, and SstI. A small number of bands were seen, with distinct differences
      between the nitrate-positive and the nitrate-negative strains. No genetic
      variations were seen between strains which reflected differences in carbohydrate
      fermentation. Strains isolated from different animal species and from different
      parts of the world could not be differentiated genetically using these three
      restriction enzymes.

PMID- 8861639
TI  - Partial purification and characterization of Salmonella cytotoxin.
AB  - The cytotoxins of two strains of Salmonella enterica subspecies enterica serovar
      Nchanga (MP2309) and Virchow (MP1871) were partially purified and characterized
      physicochemically. The toxin was salt-precipitable and non-dialysable. Upon
      filtration through Sephadex G-100 gel column, the toxicity was observed mainly in
      2nd peak. The cytotoxic activity was lost completely when heated at 121 degrees C
      for 15 min. The toxin was found active between a narrow range of pH (i.e., 6.0 to
      9.0). The cytotoxic activity was destroyed by treatment with trypsin and protease
      but the activity was not affected by papain.

PMID- 8861640
TI  - Motility and chemotaxis in Serpulina hyodysenteriae.
AB  - Chemotactic- or motility-regulated mucus association appears to be the
      predominant mechanism of mucosal association by the causative agent of swine
      dysentery, Serpulina hyodysenteriae. In the present study, a modification of the
      Adler capillary assay was used to evaluate the chemotactic responses of S.
      hyodysenteriae to a variety of potential stimuli. First, however, it became
      necessary to study factors that influenced motility of the spirochete in vitro,
      since standard cultivation methods produced motility inferior to that observed
      for in vivo grown cells. A number of factors were found to influence S.
      hyodysenteriae motility, but of these growth medium and growth phase appeared to
      be the most important. The type and even batch of culture medium also were found
      to have a significant influence on S. hyodysenteriae motility. Optimal motility
      and chemotaxis for S. hyodysenteriae was observed when the cells were harvested
      in mid- to late-log phase, and in vivo-like motility could be induced by
      suspending the cells in physiologic saline. S. hyodysenteriae was strongly
      attracted to hog gastric mucin, certain concentrations of blood, L-fucose, L
      serine and other compounds. Selected sugars and other amino acids did not serve
      as chemoattractants for S. hyodysenteriae. The chemotactic response of S.
      hyodysenteriae toward L-fucose and L-serine, constituents of mucin, may be
      important factors in the affinity of the spirochete for the mucus in the
      intestinal tract of swine.

PMID- 8861641
TI  - A PCR scheme for differentiation of organisms belonging to the Mycoplasma
      mycoides cluster.
AB  - Rapid and specific detection of organisms belonging to the Mycoplasma mycoides
      cluster, among them Mycoplasma (M.) mycoides subsp. mycoides SC, the agent of
      contagious bovine pleuropneumonia, is an important condition for effective
      control of the respective animal diseases. In an effort to improve diagnosis, a
      PCR identification scheme for these mycoplasmas was developed. A set of primer
      combinations derived from the CAP-21 genomic regions of member organisms of the
      Mycoplasma mycoides cluster was selected by means of which complete
      differentiation within the cluster can be accomplished. Nested PCR involving
      cluster-specific amplification at the first stage and group-specific
      amplification using internal primers at the second stage was shown to be
      applicable for identification of all six groups forming the cluster. For example,
      external primers P1 /P2 and internal primers P6/P7 were used to distinguish M.
      mycoides subsp. mycoides SC from LC strains. Using the present PCR procedure,
      identification of mycoplasmas could be considerably accelerated in comparison to
      conventional methods (5 h vs. one week) and specificity was also improved.

PMID- 8861642
TI  - Optimising the conditions for isolation of Mycoplasma gallisepticum collected on
      applicator swabs.
AB  - An experiment to compare the recovery of Mycoplasma gallisepticum (Mg) on dry
      swabs and swabs wet with mycoplasma broth (MB) was carried out by swabbing
      choanal clefts of Mg infected turkey poults at days 3, 6, 9, 12 post-infection.
      Wet swabs yielded significantly greater numbers of mycoplasmas than dry swabs on
      three out of four sampling days. When low numbers of mycoplasmas were collected
      on wet or dry swabs (in vitro) and then stored at room temperature (RT) or 4
      degrees C for various intervals, those on dry swabs at RT had lost viability by 8
      to 24 h. They survived at least 24 h on wet swabs kept at 4 degrees C. When Mg
      was collected and stored on dry and wet swabs from experimentally infected poults
      survival was again best on wet swabs stored at 4 degrees C. Swabs pre-wet with MB
      and stored before sampling could be used without any ill effects on mycoplasma
      recovery as long as they were stored at 4 degrees C and for no more than 48 h.
      After storage at RT for 48 h such swabs appeared to be detrimental to the
      organism. Mg collected on wet charcoal swabs was viable for 48 to 72 h when kept
      at 4 degrees C whereas it was viable for only 24 h when stored at RT. Mg was
      recovered from wet charcoal swabs sent through the mail but not from dry or wet
      plain swabs.

PMID- 8861643
TI  - Effect of bovine herpesvirus-1 on expression of interleukin-2 receptors and
      effect of interleukin-12 on lymphocyte proliferation.
AB  - Expression of the interleukin-2 receptor alpha chain (IL-2R alpha) by peripheral
      blood mononuclear cells (PBMC) from Holstein calves, both experimentally-infected
      with bovine herpesvirus-l (BHV-l) and controls, was measured by flow cytometry.
      Expression of IL-2R alpha was 35 percent and 23 percent higher in infected calves
      than controls, on days 2 and 3 postinfection (PI), respectively. Concurrent with
      this increase in IL-2R alpha expression, a significant decrease (P < 0.001) was
      observed in the PHA-induced proliferative responses of PBMC from infected
      compared with control calves. In vitro treatment with recombinant human (rhu) IL
      12 enhanced PHA-induced proliferative responses of PBMC from both infected and
      control calves. This rhuIL-12 enhancement of mitogen-induced proliferative
      responses was significant (P < 0.001) in infected calves on day 2 PI and was
      sufficient to abrogate the decrease observed due to BHV-1 infection. Since the
      expression of the beta and gamma chains of IL-2R was not measured it is difficult
      to speculate as to the status of high affinity receptor expression during BHV-1
      infection. However results of the present study suggest that the decrease in
      proliferative responses observed during infection may not be due to a decrease in
      IL-2R alpha expression but may possibly be due to a selective down-regulation of
      signal transduction through IL-2R and/or by modulation of the expression of other
      cytokines involved in lymphocyte activation and proliferation.

PMID- 8861644
TI  - Identification of bovine viral diarrhea virus receptor in different cell types.
AB  - Anti-idiotypic antibodies (anti-ids) have been used successfully in studies on
      bovine viral diarrhea virus (BVDV) receptor(s) in our laboratory. The anti-ids
      specifically bound to cultured cells and identified a 50 kDa cellular membrane
      protein, which is thought to be a specific receptor for BVDV. In this study, flow
      cytometric analyses demonstrated that the anti-ids also specifically bound to
      different cell types, namely MDBK, EBK, BT, PK15, MA1O4, and Vero. Experiments on
      virus attachment and replication showed that BVDV adsorbed to all cells and
      replicated in them except monkey kidney cells MA 104 and Vero (non-permissive).
      Results from plaque reduction assays indicated that cellular membrane proteins
      from all cell lines competitively inhibited BVDV attachment to cultured MDBK
      cells, suggesting the presence of BVDV receptor on all cells. Immunoblotting of
      cell membrane proteins with the anti-ids revealed a 50 kDa protein in both
      permissive and nonpermissive cells. Subcloned or synchronized MDBK cells
      demonstrated no significant difference of binding with anti-ids as compared to
      normal cultured cells.

PMID- 8861645
TI  - Rapid and high sensitivity test for direct detection of bovine herpesvirus-1
      genome in clinical samples.
AB  - A procedure for direct detection of the BHV-1 genome in clinical samples,
      including semen, was developed. The method is based on the PCR amplification of a
      highly conserved DNA fragment within the glycoprotein gI sequence of the virus
      (323 bp between nt 1491 to nt 1814). The method is rapid and highly specific for
      all 27 subtypes assayed, which are included in the clinical and genetically
      different groups of BHV-1. The viral origin of the PCR product was assessed by
      Southern hybridization, with an internal probe. The method for DNA isolation from
      clinical samples included a fast extraction procedure with Chelex 100 resin
      allowing the loading of larger amounts of DNA in the PCR and in turn increasing
      the sensitivity of the method of detection. The level of sensitivity achieved by
      PCR was in the range of 1 TCID(50). This PCR assay may be an useful tool for BHV
      1 monitoring in semen banks at low cost.

PMID- 8861646
TI  - Electron microscope studies of the replication of a British isolate of maedi
      visna virus in macrophages and skin cell lines.
AB  - The replication of EV1, a British isolate of maedi visna virus (MVV), in
      macrophages has not previously been studied. We therefore used transmission and
      scanning electron microscopy (TEM and SEM respectively) to compare the
      replication of EV1 in macrophages versus skin cell lines. Monocyte-derived
      macrophages (MDM), alveolar macrophages (AM) and skin cell lines were all
      permissive for replication by EV1. Virus grew rapidly and to high titers in skin
      cell lines and mature MDM. However replication was slower in less mature MDM or
      AM. Virion budding occurred through (i) cytoplasmic membranes only (skin cells),
      (ii) cytoplasmic and vesicular membranes (MDM) or (iii) vesicular membranes only
      (AM). This meant that virions accumulated in vacuoles within macrophages.
      Retroviral intracytoplasmic type A particles were seen in the cytoplasm of AM and
      MDM infected with strain EV1, but not MDM infected with strain 1514 (an Icelandic
      MVV strain) and were shown to contain MVV gag antigen by immunogold staining.

PMID- 8861647
TI  - Diagnosis of porcine reproductive and respiratory syndrome using infected
      alveolar macrophages collected from live pigs.
AB  - A highly sensitive method of detecting infection of live pigs with porcine
      reproductive and respiratory syndrome virus (PRRSV) was developed by testing
      alveolar macrophages collected by pulmonary lavage. Five pigs were exposed by
      oronasal inoculation or by contact to PRRSV when they were 10 (1 pig) or 14 weeks
      (4 pigs) of age. Diagnostic samples (alveolar macrophages and sera) were
      collected from each pig just before exposure to PRRSV. During the next 9 weeks
      sera were collected at weekly intervals and alveolar macrophages were collected
      at weeks 2 and 4-9. Both sera and alveolar macrophages were suitable for
      detecting early infection, but alveolar macrophages were clearly the better
      sample after longer intervals. Virus was last isolated from serum at week 4 (from
      1 of 5 pigs), whereas it was isolated from the alveolar macrophages of 4 of the 5
      pigs at week 4 and from at least 2 pigs at each of the weekly intervals
      thereafter (i.e. weeks 5, 6, 7, 8, and 9 postexposure). The most sensitive method
      of testing alveolar macrophages for PRRSV was cocultivation with MARC-145 cells.
      None of the pigs had any clinical signs after exposure to PRRSV or as a result of
      pulmonary lavage and there was no evidence that repeated pulmonary lavage caused
      anything other than a mild, transient (mild hyperemia) tissue reaction.

PMID- 8861648
TI  - Evaluation of a competitive enzyme-linked immunosorbent assay to detect infection
      of cattle in sentinel herds in Queensland, Australia with bluetongue viruses.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) was used to detect
      serogroup specific antibodies to bluetongue viruses. This test is commercially
      available and was evaluated with serially collected sera from 10 sentinel herds
      of cattle maintained in Queensland, Australia during 1994. Determination of an
      infection during the period of observation was based on the development of a
      serum neutralisation (SN) test titre > or = 1:8 to any one of 8 bluetongue virus
      serotypes known to exist in Australia. Using the inhibition value of 40%
      recommended by the manufacturer to classify cattle as exposed to bluetongue
      viruses, the ELISA was highly sensitive (100%; 95% confidence interval, 77.9
      100%) and moderately specific (86.4%; 95% CI, 77.0-93.0%), relative to the SN
      test. An inhibition value of 70% maximised both sensitivity (100%, lower 95% CI,
      77.9%) and specificity (93.2%, 95% CI, 85.2-98.0%) of the ELISA. The chance
      (posttest probability) of an animal from which a serum sample had an inhibition
      value > or = 70 % in the ELISA developing an SN test titre > or = 1:8 was 93.6%
      (95% CI, 86.4-97.9%). Investigations of the temporal development of ELISA and SN
      test reactions, showed that the ELISA detected exposure to bluetongue viruses
      significantly (P = 0.0156) earlier than the SN test. The bluetongue virus ELISA
      is a useful test in surveillance programs. False positive assay results make it
      inappropriate for monitoring and diagnosis, unless it is used in conjunction with
      the SN test.

PMID- 8861649
TI  - Noncytopathogenic and cytopathogenic bovine viral diarrhea-mucosal disease
      viruses do not affect in vitro embryonic development into the blastocyst stage.
AB  - Bovine oocytes enclosed within follicular epithelial (FE) cells were exposed to
      noncytopathogenic or cytopathogenic strains of bovine viral diarrhea-mucosal
      disease virus (BVD-MDV). After culture at 39 degrees C in humidified air with 5
      percent CO2 for 24 h, the oocytes matured and then in vitro fertilization was
      performed. Some of the fertilized oocytes developed into blastocysts from day 8
      to day 10 (day 1: date of insemination), and the rate of development to
      blastocysts was the same as for the unexposed control oocytes. In the
      developmental medium, each strain of BVD-MDV was present at 10(3) to 10(6) TCID
      (50)/0.25 ml from day 3 to day 10, respectively and the virus was isolated from
      the FE cells at high titers and from the embryos at low titers on day 10. BVD-MDV
      antigen was detected in the cytoplasm of the FE cells by indirect
      immunofluorescence. These findings indicate that BVD-MDV replicates well in FE
      cells. The results of this study suggest that BVD-MDV replication in cells around
      embryos has no effect on bovine embryo development.

PMID- 8861650
TI  - Comparison of camelpox viruses isolated in Dubai.
AB  - Between October 1993 and March 1994, outbreaks of pox-like exanthemas were
      observed in several camel raising farms in Dubai. Scabs from twenty camels with
      either local or generalized lesions were examined, seven of them had previously
      been vaccinated with a modified live camelpox virus vaccine. Inspection of scabs
      by electron microscopy confirmed an infection with orthopox viruses (OPV) in 10
      animals and with parapox virus in one camel. Investigation of the scabs by
      polymerase chain reaction and dot blot assay revealed the presence of OPV in 15
      or 13 samples, respectively. OPV could be isolated in cell culture in 14 cases.
      Restriction enzyme profiles characterized all isolates as camelpox virus. Their
      DNA patterns were virtually identical displaying only slight variations in the
      terminal fragments. In contrast, the vaccine strain showed a distinct restriction
      enzyme profile, indicating that it was not involved in the infections.

PMID- 8861651
TI  - Canine distemper virus infection in Serengeti spotted hyenas.
AB  - Clinical signs suggestive of canine distemper virus (CDV) infection were observed
      among a group of spotted hyenas (Crocuta crocuta) in the Serengeti, Tanzania.
      Virus antigen was detected immunohistologically in a brain sample from a diseased
      cub. The presence of virus RNA could be demonstrated in this brain as well as in
      intestine and lymph node of the animal by RT-PCR. Sequence comparison of brain
      derived amplicons showed that the virus was related to recent CDV field isolates.
      The closest homology (>99 percent) was to a recently described CDV which caused
      high mortality in sympatric lions.

PMID- 8861652
TI  - Two-step chromatographic purification of human plasma alpha(1)-acid glycoprotein:
      its application to the purification of rare phenotype samples of the protein and
      their study by chromatography on immobilized metal chelate affinity adsorbent.
AB  - Alpha1-Acid glycoprotein (AAG) or orosomucoid was purified to homogeneity from
      human plasma by a separate two-step method using chromatography on immobilized
      Cibacron Blue F3G-A to cross-linked agarose and chromatography on hydroxyapatite.
      The conditions for the pre-purification of AAG by chromatography on immobilized
      Cibacron Blue F3G-A were first optimized using different buffer systems with
      different pH values. The overall yield of the combined techniques was 80% and ca.
      12 mg of AAG were purified from an initial total amount of ca. 15 mg in a ca. 40
      ml sample of human plasma. This method was applied to the purification of AAG
      samples corresponding to the three main phenotypes of the protein (FI*S/A, F1/A
      and S/A), from individual human plasma previously phenotyped for AAG. A study by
      isoelectric focusing with carrier ampholytes showed that the microheterogeneity
      of the purified F1*S/A, F1/A and S/A AAG samples was similar to that of AAG in
      the corresponding plasma, thus suggesting that no apparent desialylation of the
      glycoprotein occurred during the purification steps. This method was also applied
      to the purification of AAG samples corresponding to rare phenotypes of the
      protein (F1/A*AD, S/A*X0 and F1/A*C1) and the interactions of these variants with
      immobilized copper(II) ions were then studied at pH 7, by chromatography on an
      iminodiacetate Sepharose-Cu(II) gel. It was found that the different variants
      encoded by the first of the two genes coding for AAG in humans (i.e. the F1 and S
      variants) interacted non-specifically with the immobilized ligand, whereas those
      encoded by the second gene of AAG (i.e. the A, AD, X0 and C1 variants) strongly
      bound to immobilized Cu(II) ions. These results suggested that chromatography on
      an immobilized affinity Cu(II) adsorbent could be helpful to distinguish between
      the respective products of the two highly polymorphic genes which code for human
      AAG.

PMID- 8861653
TI  - Thiopurine methyltransferase: a review and a clinical pilot study.
AB  - Thiopurine methyltransferase (TPMT) is an important enzyme in the metabolism of 6
      mercaptopurine (6MP), which is used in the treatment of acute lymphoblastic
      leukemia (ALL). TPMT catalyzes the formation of methylthioinosine monophosphate
      (MetIMP), which is cytotoxic for cultured cell lines, and it plays a role in
      detoxification of 6MP. Population studies show a genetic polymorphism for TPMT
      with both high and low activity alleles. About 1 of 300 subjects is homozygous
      for the low activity. The function TPMT plays in detoxification or therapeutic
      efficacy of 6MP in vivo is not clear. In this article the genetic polymorphism of
      TPMT is reviewed and the contribution of TPMT to the cytotoxic action, or
      detoxification, of 6MP in children with ALL is discussed. Induction of TPMT
      activity has been described during the treatment for ALL. We performed a pilot
      study on the influence of high-dose 6MP infusions (1300 mg/m2 in 24 h) on TPMT
      activity of peripheral blood mononuclear cells (pMNC) of eleven patients with
      ALL. The TPMT activities were in, or, above the normal range. There was no
      statistically significant difference between the TPMT activities before and after
      the 6MP infusions. MetIMP levels in pMNC increased during successive courses.
      This might be explained by TPMT induction, but other explanations are plausible
      as well. Twenty five percent of the TPMT assays failed, because less than the
      necessary 5.10(6) pMNC could be isolated from the blood of leukopenic patients.
      Red blood cells can not be used for TPMT measurements, since transfusions are
      frequently required during the treatment with 6MP infusions. Therefore, the
      influence of high-dose 6MP infusions on TPMT activity can only be investigated
      further when a TPMT assay which requires less pMNC has been developed.

PMID- 8861654
TI  - Clinical chemistry of common apolipoprotein E isoforms.
AB  - Apolipoprotein E plays a central role in clearance of lipoprotein remnants by
      serving as a ligand for low-density lipoprotein and apolipoprotein E receptors.
      Three common alleles (apolipoprotein E(2), E(3) and E(4)) give rise to six
      phenotypes. Apolipoprotein E(3) is the ancestral form. Common apolipoprotein E
      isoforms derive from nucleotide substitutions in codons 112 and 158. Resulting
      cysteine-arginine substitutions cause differences in: affinities for low-density
      lipoprotein and apolipoprotein E receptors, low-density lipoprotein receptor
      activities, distribution of apolipoprotein E among lipoproteins, low-density
      lipoprotein formation rate, and cholesterol absorption. Accompanying changes in
      triglycerides, cholesterol and low-density lipoprotein may promote
      atherosclerosis development. Over 90% of patients with familial
      dysbetalipoproteinaemia have apolipoprotein E(2)/E(2). Apolipoprotein E(4) may
      promote atherosclerosis by its low-density lipoprotein raising effect.
      Establishment of apolipoprotein E isoforms may be important for patients with
      diabetes mellitus and several non-atherosclerotic diseases. Apolipoprotein E
      phenotyping exploits differences in isoelectric points. Isoelectric focusing uses
      gels that contain pH 4-7 ampholytes and urea. Serum is directly applied, or
      prepurified by delipidation, lipoprotein precipitation or dialysation.
      Isoelectric focusing is followed by immunofixation/protein staining. Another
      approach is electro- or diffusion blotting, followed by protein staining or
      immunological detection with anti-apolipoprotein E antibodies and an enzyme
      conjugated second antibody. Apolipoprotein E genotyping demonstrates underlying
      point mutations. Analyses of polymerase chain reaction products are done by
      allele-specific oligonucleotide probes, restriction fragment length polymorphism,
      single-stranded conformational polymorphism, the primer-guided nucleotide
      incorporation assay, or denaturating gradient gel electrophoresis. Detection with
      primers that either or not initiate amplification is performed with the
      amplification refractory mutation system. Disparities between phenotyping and
      genotyping may derive from isoelectric focusing methods that do not adequately
      separate apolipoprotein E posttranslational variants, storage artifacts or faint
      isoelectric focusing bands.

PMID- 8861655
TI  - Characterization of the genetic polymorphism of dihydrocodeine O-demethylation in
      man via analysis of urinary dihydrocodeine and dihydromorphine by micellar
      electrokinetic capillary chromatography.
AB  - The genetic polymorphism of dihydrocodeine O-demethylation in man via analysis of
      urinary dihydrocodeine (DHC) and dihydromorphine (DHM) by micellar electrokinetic
      capillary chromatography is described. Ten healthy subjects which are known to be
      extensive metabolizers for debrisoquine ingested 60 mg of DHC and collected their
      0-12 h urines. In these samples, about 1% of the administered DHC equivalents are
      shown to be excreted as DHM. Premedication of 50 mg quinidine sulfate to the same
      subjects is demonstrated to significantly reduce (3-4 fold) the amount of O
      demethylation of DHC, a metabolic step which is thereby demonstrated to co
      segregate with the hydroxylation of debrisoquine. Thus, in analogy to codeine and
      other substrates, extensive and poor metabolizer phenotypes for DHC can be
      distinguished. Using the urinary DHC/DHM metabolic ratio to characterize the
      extent of O-demethylation, the metabolic ratio ranges of extensive and poor
      metabolizers in a frequency histogram are shown to partially overlap. Thus,
      classification of borderline values is not unequivocal and DHC should therefore
      not be employed for routine pharmacogenetic screening purposes. Nevertheless, the
      method is valuable for metabolic research and preliminary data demonstrate that
      the same assay could also be used to explore the metabolism of codeine.

PMID- 8861656
TI  - Use of electrospray ionization liquid chromatography-mass spectrometry to study
      the role of CYP2D6 in the in vitro metabolism of 5-hydroxytryptamine receptor
      antagonists.
AB  - An electrospray ionization liquid chromatographic-mass spectrometric (ESI-LC-MS)
      method has been developed to study the involvement of the cytochrome P450
      isoenzyme CYP2D6 in the in vitro metabolism of the indole containing 5
      hydroxytryptamine (5-HT(3)++) receptor antagonists tropisetron, ondansetron and
      dolasetron in human liver microsomes. Compounds were eluted using linear
      gradients of acetonitrile-20 mM ammonium acetate, solvent A, (10:90, v/v) (pH
      6.0) and solvent B, (60:40, v/v) (pH 6.0) and a Nucleosil C(4) column. Microsomal
      incubations were analysed using selected ion monitoring of the molecular ion of
      parent drug and the molecular ion of hydroxylated metabolites. The involvement of
      CYP2D6 in drug metabolism was assessed by inhibition studies using quinidine (5
      mu M), a specific inhibitor of human CYP2D6, as well as by incubating compounds
      with microsomes prepared from cells transfected with cDNA encoding human CYP2D6.
      Results showed that the oxidation of all three compounds involved CYP2D6, but
      only that of tropisetron was inhibited by over 90% in the presence of quinidine.
      The present method can be applied to pre-clinical compounds, at an early stage of
      drug discovery, to assess the involvement of CYP2D6 in their metabolism and to
      screen for those compounds where CYP2D6 is the only isoenzyme implicated in the
      formation of major metabolites.

PMID- 8861657
TI  - Simultaneous determination of nerisopam, a novel anxiolytic agent showing
      polymorphic metabolism, and its N-acetyl metabolite from human plasma by a
      validated high performance liquid chromatographic method.
AB  - A sensitive reversed-phase high-performance liquid chromatographic method with
      ultraviolet absorbance detection has been developed to simultaneously determine
      the concentrations of nerisopam (EGIS-6775) and its N-acetyl metabolite (EGIS
      7649) from human plasma. The separation of the investigated compounds and
      internal standard was achieved on a Nucleosil 7 C(18) column with 2 mM
      heptanesulphonic acid containing 0.04 M phosphoric acid-acetonitrile-methanol
      (70:25:5, v/v), pH 2.7 mobile phase. The detection was performed at 385 nm. The
      compounds were isolated from plasma by Bakerbond C(18) solid-phase extraction.
      The limit of quantitation was 10 ng/ml plasma for each compound investigated. The
      assay has been validated with respect to accuracy, precision and system
      suitability. All validated parameters were found to be within the necessary
      limits. On the basis of the sensitivity, linearity and validation parameters, the
      developed analytical method was found to be suitable for the determination of
      nerisopam and its N-acetyl metabolite from human plasma and for application in
      pharmacokinetic studies and human drug monitoring. The pharmacokinetic parameters
      obtained from twelve human volunteers are reported. It was found that nerisopam
      acetylation is polymorphic: the volunteers with fast or slow acetylator
      phenotypes produced significantly different plasma concentrations. In slow
      acetylator phenotypes the concentration of nerisopam was considerably higher in
      plasma, while the level of its acetyl metabolite was higher in plasma of fast
      acetylators.

PMID- 8861658
TI  - Investigation of xenobiotic metabolism by CYP2D6 and CYP2C19: importance of
      enantioselective analytical methods.
AB  - Investigations into the genetic polymorphism of drug metabolism have involved
      specific models to screen poor and extensive metabolisers of xenobiotics.
      Debrisoquine, sparteine, S-mephenytoin and dextromethorphan are particularly well
      known. They have been extensively described in the literature and are used to
      phenotype human subjects before performing investigations with new drugs which
      are believed to be under the control of a genetic polymorphism. Dextromethorphan,
      debrisoquine and sparteine are good substrates for CYP2D6, whereas the S
      enantiomer of mephenytoin is a good substrate for CYP2C19, both being two
      isozymes of cytochrome P-450. In many drugs, the hepatic microsomal oxidative
      metabolism involving stereogenic centres congregates either with CYP2D6 or with
      CYP2C19 or, in certain cases, with both of them. The availability of both CYP2D6
      from poor and extensive metabolisers and an enantioselective assay would allow
      genetic polymorphism in drug biotransformation to be investigated in vitro ex
      vivo at an early stage of drug development before the IND (investigational new
      drug). Single-dose investigations in vivo can also be performed when only minimal
      pre-clinical toxicological data are available and produce more reliable results
      than in vitro studies. This paper focuses on the problem of genetic polymorphism
      in drug development and specifically discusses some relevant knowledge gained in
      the last two decades on enantioselective bioassays. Specific examples are given.

PMID- 8861659
TI  - Prediction of CYP2D6-mediated polymorphic drug metabolism (sparteine type) based
      on in vitro investigations.
AB  - Discovery of genetic polymorphism in drug metabolism has contributed a great deal
      to understanding the variability in dose-concentration relationships introduced
      by genetic factors, thereby elucidating the mechanisms responsible for unexpected
      drug reactions. This knowledge should find its way into clinical practice in
      order to make therapy more efficient and safe. Moreover, genetic factors in drug
      metabolism should be taken into account during drug development. Therefore, in
      vitro methods for identifying the metabolic pattern of new compounds during early
      stages of drug development should be improved. This review summarizes in vitro
      methods available to identify genetic polymorphism in drug oxidation, in
      particular the CYP2D6-related polymorphism.

PMID- 8861660
TI  - Quantification of dextromethorphan and metabolites: a dual phenotypic marker for
      cytochrome P450 3A4/5 and 2D6 activity.
AB  - A sensitive and selective liquid chromatographic procedure using fluorimetric
      detection was developed to quantify dextromethorphan (DTM), 3-methoxymorphinan
      (3MM), dextrorphan (DT), 3-hydroxymorphinan (3OH) and two internal standards,
      codeine (COD) and ethylmorphine (ETM), in urine. Precision and accuracy of the
      assay were determined over a concentration range of 5-3200 ng/ml urine for DTM, 5
      400 ng/ml urine for 3MM, 400-40 000 ng/ml urine for DT and 200-16 000 ng/ml urine
      for 3OH, by assaying freshly prepared calibration standards and replicates of six
      quality control (QC) samples on separate days. All of the inter-day and intra-day
      coefficients of variation (C.V.s) were less than 20% except for a low QC for 3MM.
      The inter-day and intra-day accuracies were less than 20% for the low QCs, less
      than 15% for the medium QCs and less than 12% for the high QCs, for all
      compounds. The limit of quantification (LOQ) was 2 ng/ml urine for DTM and 3MM,
      250 ng/ml urine for DT, and 100 ng/ml urine for 3OH. Absolute recovery was 76%
      for DTM, 74% for 3MM, 77% for DT, 46% for 3OH, 73% for ETM, and 57% for COD. The
      frequency distribution of the CYP2D6 metabolic ratio (DTM/DT) illustrated a
      bimodal distribution whereas, the CYP3A metabolic ratio (DTM/3MM) exhibited a
      unimodal distribution in overnight urine samples of volunteers who ingested 30 mg
      dextromethorphan hydrobromide. The CYP2D6 metabolic ratio significantly
      correlated with 3MM/3OH (r=0.82) and DTM/3OH (r=0.95) but did not correlate with
      the CYP3A metabolic ratio (r=0.27).

PMID- 8861661
TI  - Dextromethorphan as an in vivo probe for the simultaneous determination of CYP2D6
      and CYP3A activity.
AB  - Dextromethorphan (DM) is O-demethylated into dextrorphan (DEX) in humans by the
      cytochrome P450 designated as CYP2D6 and N-demethylated into 3-methoxymorphinan
      (3MM) via CYP3As. Clinically, DM has been successfully used as an index of CYP2D6
      and this paper describes analytical and clinical data that will help evaluate the
      use of DM hydrobromide as a probe of CYP3A activity. DM and its three
      demethylated metabolites were measured in a 4-h spot urine sample using a HPLC
      method employing solid-phase extraction (C(18)), analysis on a phenyl column
      [mobile phase, methanol-acetonitrile-phosphate buffer (10 mM, pH 3.5, 20:25:55,
      v/v)] and fluorescence detection (excitation at lambda=228 nm, no emission cut
      off filter). The urinary molar ratio DM-DEX was used to assess CYP2D6 activity
      while DM-3MM was used for CYP3As. The DM-3MM ratios were sensitive to the co
      administration of selective CYP3A inhibitors grapefruit juice and erythromycin.
      In addition, in healthy volunteers and cancer patients, the N-demethylation of DM
      correlated with the CYP3A-mediated metabolism of verapamil and tamoxifen. DM
      appears to be a promising way to simultaneously phenotype patients for CYP2D6 and
      CYP3As.

PMID- 8861662
TI  - Effects of water and ambient air temperatures on human diving bradycardia.
AB  - Upon apnoeic face immersion, humans develop a diving response resembling that
      found in diving mammals. There have been contradictory reports regarding the
      influence of water temperature on the magnitude of the resulting bradycardia.
      This study examined the influence of both water and ambient air temperatures on
      human diving bradycardia. A group of 23 volunteers performed three series of
      apnoeic episodes after 60 min exposure to air at temperatures of 10, 20 or 30
      degrees C. Oral and skin temperatures were measured during this exposure and
      during the subsequent test on 5 subjects. At 20 degrees C air temperature oral
      and skin temperatures were measured on 10 subjects. Heart rate (HR) was recorded
      for the 23 subjects during apnoea in air and apnoea with the face immersed in
      water of 10, 20 or 30 degrees C, at each air temperature. We found that both air
      and water temperatures had significant effects on immersion bradycardia, but in
      opposite directions. Face immersion in cold water after exposure to a high
      ambient air temperature induced the most pronounced bradycardia. We further
      observed that exposure to different ambient air temperatures resulted in
      different patterns of HR response to water temperature. The range in which the
      response was positively correlated to water temperature differed at 30 degrees C
      ambient air from that at 10 and 20 degrees C ambient air. We concluded from these
      studies that human bradycardia resulting from apnoeic face immersion is inversely
      proportional to water temperature within a range which is determined by the
      ambient air temperature. Thus, the interval in which the response to cold
      stimulation varies with temperature, would appear to be determined by the ambient
      temperature before stimulation.

PMID- 8861663
TI  - Age-related changes in biomechanical properties of the Achilles tendon in
      rabbits.
AB  - We investigated age-related changes in the mechanical properties of rabbit
      Achilles tendon. The animals used were immature (age 3 weeks, body mass 380 g),
      young adult (age 8-10 months, body mass 4.1 kg) and old (age 4-5 years, body mass
      5.1 kg) rabbits. The cross-sectional area of the tendon increased with growth and
      the tensile strength of the young adult [67.3 (SEM 4.2) MPa] and old [66.7 (SEM
      3.8) MPa] tendon was significantly higher than that of the immature tendon [23.9
      (SEM 3.8) MPa]. However, there was no statistically significant difference in
      tensile strength between mature and old tendons. These differences may be
      attributable to the change in body mass. The gradient of the stress-strain
      curves, that is, the tangent modulus of the mature tendon [618.0 (SEM 87.0) MPa],
      was higher than that of the immature [281.0 (SEM 104.6) MPa] and old [530.5 (SEM
      91.0) MPa] tendon, although the difference was not significant. The elongation at
      failure was approximately 16 percent for all age groups. These results would
      suggest that rabbit Achilles tendon is highly compliant during growth.

PMID- 8861664
TI  - Erythropoietin in 29 men during and after prolonged physical stress combined with
      food and fluid deprivation.
AB  - The study investigated the influence of prolonged physical stress during survival
      training with food and fluid deprivation on the serum concentrations of
      erythropoietin (EPO). A group of 29 male subjects [mean age 22.2 (SD 2.8) years,
      height 1.78 (SD 0.06) m, and body mass (m(b)) 73.5 (SD 8.6) kg] were studied for
      5 days of multifactorial stress including restricted water intake (11 H2O. day(
      1)) and food intake (628 kJ. day(-1)) combined with physical exercise (estimated
      energy expenditure approximately 24000 kJ.day(-1)) and sleep deprivation (20 h
      within 5 days). Blood samples were taken before (T1), after 72 h (T2) and 120 h
      (T3) of physical stress, and after 48 h, (T4) and 72 h (T5) of recovery. The
      samples were analysed for EPO, and concentrations of serum iron (Fe), haptoglobin
      (Hapto), transferrin (Trans), ferritin (Fer), haemoglobin (Hb) and packed cell
      volume (PCV). The m(b) had decreased by 6.77 kg at T3 (P <0.01) and 0.68 kg at
      T5. The EPO and Hapto decreased during the survival training (P <0.01) and
      increased during the recovery period (P <0.01). The Fe increased during the
      survival training (P <0.01) and remained above the control concentrations during
      recovery (P <0.01). The Hapto decreased during the survival training (P <0.01)
      and remained below control concentration at T4 and T5 (P <0.01). The Trans
      decreased continuously over the week (P <0.01). The Fer increased during the
      survival training (P <0.01) and returned to control concentration at T5. The Hb
      increased from T1 to T2 (P <0.01) and had decreased significantly at T5 (P
      <0.01). The PCV increased from T1 to T2 (P <0.01) and remained below control
      levels afterwards (P <0.01). From our study it was concluded that, in humans,
      prolonged physical stress with food and fluid deprivation induces a marked EPO
      decrease, which is followed by a rapid increase during recovery to restore the
      reduced O2 transport capacity.

PMID- 8861665
TI  - Effects of cyclo-oxygenase inhibition on ozone-induced respiratory inflammation
      and lung function changes.
AB  - Inhalation of O3 causes airways neutrophilic inflammation accompanied by other
      changes including increased levels of cyclo-oxygenase products of arachidonic
      acid in bronchoalveolar lavage fluid (BALF). Ozone O3 exposure also causes
      decreased forced vital capacity (FVC) and forced expiratory volume after 1 s
      (FEV(1)), associated with cough and substernal pain on inspiration, and small
      increases in specific airway resistance (SRAW). The spirometric decrements are
      substantially blunted by pretreatment with indomethacin. Since the O3-induced
      decrement in FVC is due to involuntary inhibition of inspiration, a role for
      stimulation of nociceptive respiratory tract afferents has been suggested and
      cyclo-oxygenase products have been hypothesized to mediate this stimulation.
      However, the relation (if any) between the O3-induced neutrophilic airways
      inflammation and decreased inspiratory capacity remains unclear. We studied the
      effects of pharmacologic inhibition of O3-induced spirometric changes on the
      inflammatory changes. Each of ten healthy men was exposed twice (5-week interval)
      to 0.4 ppm O3 for 2 h, including 1 h of intermittent exercise (ventilation
      601*min(-1)). One-and-a-half hours prior to and midway during each exposure the
      subject ingested 800 mg and 200 mg, respectively, of the non-steroidal anti
      inflammatory drug ibuprofen (IBU), or placebo [PLA (sucrose)], in randomized,
      double-blind fashion. Spirometry and body plethysmography were performed prior to
      drug administration, and before and after O3 exposure. Immediately following
      postexposure testing, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL)
      was performed. Neither IBU nor PLA administration changed pre-exposure lung
      function. O3 exposure (with PLA) caused a significant 17 percent mean decrement
      in FEV(1) (P <0.01) and a 56 percent increase in mean SRAW. Following IBU
      pretreatment, O3 exposure induced a significantly lesser mean decrement in FEV(1)
      (7 percent) but still a 50 percent increase in mean SRAW. IBU pretreatment
      significantly decreased post-O3 BAL levels of prostaglandin E2 (PGE2) by 60.4
      percent (P <0.05) and thromboxane B(2) (TxB(2)) by 25.5 percent (P <0.05). Of the
      proteins, only interleukin-6 was significantly reduced (45 percent, P <0.05) by
      IBU as compared to PLA pretreatment. As expected, O3 exposure produced
      neutrophilia in BALF. There was, however, no effect of IBU on this finding. None
      of the major cell types in the BALF differed significantly between pretreatments.
      We found no association between post-exposure changes of BALF components and
      pulmonary function decrements. We conclude that IBU causes significant inhibition
      of O3-induced increases in respiratory tract PGE(2) and TxB(2) levels concomitant
      with a blunting of the spirometric response. This is consistent with the
      hypothesis that the products of AA metabolism mediate inhibition of inspiration.
      However, IBU did not alter the modest SRAW response to O3.

PMID- 8861666
TI  - Comparison of a 4-day confinement and head-down tilt on endocrine response and
      cardiovascular variability in humans.
AB  - The aim of this study was to determine the effects of a 4-day head-down tilt
      (HDT; -6 degrees) and 4-day confinement on several indicators that might reflect
      a state of cardiovascular deconditioning on eight male subjects. Measurements
      were made of endocrine responses, heart rate variability and spontaneous
      baroreflex response (SBR) slope before, during and after each intervention.
      Plasma volume decreased by 10 percent after the 4-day HDT. The concentration of
      active renin was increased and that of urinary atrial natriuretic peptide
      decreased during the 4-day experiment in both groups. Plasma arginine vasopressin
      concentration decreased significantly only after 4-day confinement. After the 4
      day HDT, one of the spectrum analysis parameters was statistically changed: the
      parasympathetic indicator decreased significantly (P <0.05) whereas the
      sympathetic indicator and the total power spectrum were unaltered. After 4-day
      confinement spectrum analysis parameters were not statistically altered. A
      significant decrease of SBR (P <0.05) was noticed only after the 4-day HDT. These
      data would suggest that exposure to a 4-day HDT was sufficient to induce a
      cardiovascular deconditioning which may have been induced by confinement and
      inactivity.

PMID- 8861667
TI  - Cardiorespiratory and metabolic adaptations to hyperoxic training.
AB  - This study examined the effects of hyperoxic training on specific
      cardiorespiratory and metabolic responses. A group of 19 male subjects trained
      for 5 weeks on a cycle ergometer at 70 percent of hyperoxic or normoxic maximal
      heart rate, the hyperoxic group (HG) breathing 70 percent O2, the normoxic group
      (NG) breathing 21 percent O2. The subjects were tested pre- and post-training
      under both hyperoxia and normoxia. Measurements included cardiac output (Q(c)),
      stroke volume (SV), heart rate (HR), pulmonary ventilation (V(E)), oxygen
      consumption (VO(2)), partial pressure of oxygen (PO(2)), partial pressure of
      inspired carbon dioxide (PCO(2)), blood lactate concentration [La], and fiber
      type composition. The V(E) was significantly lower at submaximal work rates (P
      <0.05) and maximal V(E) increased after training in both groups for both test
      conditions; hyperoxic V(E) was lower than normoxic V(E) (P <0.05). The maximal
      V0(2) increased significantly (P <0.05) in both groups for both tests and was 11
      percent - 12 percent higher during hyperoxia. Post-training maximal heart rate
      (HR(max)) was significantly decreased (P <0.05) at the same absolute work rate
      regardless of the training group or test type. The SV was increased at each work
      rate and Q c was unchanged. The maximal Q(c) increased significantly (P <0.05)
      for both groups and types of test: for normoxia: NG 27.3-30.41*min(-1) and HG
      30.3-32.31*min(-1) and for hyperoxia: NG 24.7-25.6 and HG 27.9-31.21*min(-1).
      Although working at the same intensity relative to HR(max), HG showed
      significantly lower [La] following a single training session, yet maximal values
      were unchanged after training. Both groups showed a significant increase in the
      percentage of type IIA fibers post-training but HG retained a larger percentage
      of IIB fibers. Mitochondrial enzymes; citrate kinase, 3-hydroxyacyl CoA
      dehydrogenase, and cytochrome c-oxidase were increased in the normoxic trained
      subjects (P <0.05). In summary, training induced adaptive responses in maximal
      aerobic power, HR, SV, Q(c), [La], and muscle fiber type composition, independent
      of inspired PO(2). Intramuscular data suggested there may be some differences
      between hyperoxic and normoxic training and these were substantiated by
      mitochondrial enzyme and lactate findings. Our data would suggest that transport
      mechanisms may limit the ability to increase aerobic power.

PMID- 8861668
TI  - Water balance during and after marathon running.
AB  - To describe the time course of plasma volume alterations and the changes in the
      plasma concentrations of hormones regulating water balance in relation to a
      marathon race, six experienced marathon runners (five men, one women) aged 28 (SD
      6) years were studied during and for the 3 days following a treadmill marathon
      run at 68 (SD 5) percent of maximal oxygen consumption. Haematocrit, haemoglobin,
      plasma protein (Prot) and electrolyte (Na+, K+) concentration, osmolality (osm),
      plasma concentrations of renin (Ren), aldosterone (Ald) and atrial natriuretic
      peptide (ANP) were determined at rest in a sitting position (T(-30)), and then
      after 30 min in an upright posture (R(0)), while running a marathon at 10 km
      (R(10)), 30 km (R(30)) and 42.2 km (R end), and after the marathon at 30 min
      (T(30)), 60 min (T(60)), 120 min (T(120)) and 24 h (TD(+1)), 48 h (TD(+2)) and 72
      h (TD(+3)). The changes in plasma volume (PV), Prot, osm and Na+ observed during
      the race were nonsignificant. Significant increases in plasma concentration of K+
      [4.8 (SD 0.6) vs 5.5 (SD 0.6) mmol*1(-1); P <0.01], Ren [38(SD 57) vs 197 (SD
      145) pmol*1(-1); P <0.02] and Ald [175 (SD 142) vs 1632 (SD 490) pmol*1(-1); P
      <0.01] were observed at R(end). A significant increase of ANP (P <0.05) was only
      found after R(10). Body mass significantly decreased by 2.0 kg (P <0.01) during
      the race in spite of the ingestion of 1.46 (SD 0.34)1 of a 5 percent glucose
      solution. Urinary volume and Na+ excretion dropped significantly after the
      completion of the marathon in comparison with the day before [2600 vs 1452
      ml*day(-1)(P <0.02) and 161.3 vs 97.1 mmol*1(-1) (P <0.05)]. At TD(+1) and TD(+2)
      a significant increase in PV was noted, compared to T(-30). The lack of a
      decrease in PV during the marathon may have been due to the production of 402 g
      of metabolic water and by the release of 1280 g of water stored in glycogen
      complexes in muscle and liver. Thus, the hormone response during the marathon may
      have been due to the effects of the exercise itself and not to the effects of
      dehydration. The postmarathon PV expansion may be explained by a protein shift to
      the intravascular space and by renal sodium retention.

PMID- 8861669
TI  - Electrocardiogram changes during positive pressure breathing in rabbits.
AB  - Positive pressure breathing produced by mechanical ventilation with an expiratory
      threshold load (ETL) may modify electrocardiogram (ECG) complexes independently
      of any recording artefact due to lung volume changes. Anaesthetized, paralyzed
      rabbits were treated for about 2 h, then killed. In intact then vagotomized
      animals two situations were studied successively. Firstly, positive inspiratory
      pressure breathing, and secondly, positive inspiratory plus expiratory pressure
      breathing by adding ETL to mechanical ventilation. Arterial blood gases were
      measured and held constant throughout the challenge. Oesophageal pressure, giving
      indirect measurement of intrathoracic pressure, arterial blood pressure, blood
      flows in abdominal aorta and inferior vena cava and standard ECG recordings were
      made at baseline condition during mechanical ventilation, then at the end of a 10
      min period of ETL breathing. The ETL breathing decreased arterial blood pressure
      significantly and reduced arterial and venous blood flows in the same proportion.
      No change in the duration of ECG complexes was noticed. However, ETL markedly
      reduced the amplitude of P- and T-waves, but not that of R-wave, an effect
      significantly accentuated after vagotomy. The ETL breathing increased the T
      vector angle, with no associated change in QRS vector angle. The present animal
      investigations revealed that positive pressure breathing modifies the ECG
      independently of the consequences of ETL-induced lung volume changes. We
      speculate that the changes in P- and T-wave amplitude may have resulted from a
      reduced transmural pressure gradient between the epicardium and endocardium.

PMID- 8861670
TI  - Cortisol, testosterone, and insulin action during intense swimming training in
      humans.
AB  - An increase in the amounts of circulating plasma cortisol or a decrease in
      testosterone can result in whole-body insulin resistance. The purpose of this
      study was to determine if the increase in cortisol and/or decrease in
      testosterone concentrations commonly evident with intense endurance training is
      associated with insulin resistance. Male (n = 9) and female (n = 10) swimmers
      were examined during the off-season, after 9 weeks (9 WKS) of training averaging
      5,500 m* day(-1) and after an additional 9 weeks (18 WKS) of training averaging
      8,300 m*day(-1). Resting plasma cortisol concentration was (P < or = 0.05) higher
      in the women compared to the men at 9 WKS; values were not significantly
      different between genders at 18 WKS. Plasma testosterone concentration decreased
      significantly (P < or = 0.05) in the men at 9 and 18 WKS, but did not change in
      the women. Whole-body insulin action, as determined by insulin and glucose
      responses during a 120 min, 75-g oral glucose tolerance test, did not change with
      training in either the men or women. These data indicated that plasma
      testosterone concentration can decrease in male swimmers during intense endurance
      training; this alteration does not affect wholebody insulin action. There would
      also appear to be a gender-specific response of plasma cortisol to endurance
      training, which does not influence insulin action.

PMID- 8861671
TI  - Hormonal regulation of skeletal muscle hypertrophy in rats: the testosterone to
      cortisol ratio.
AB  - This study determined the influence that the catabolic hormone, corticosterone
      (C), and the anabolic hormone, testosterone (T), had in regulating skeletal
      muscle hypertrophy using the rat hind limb ablation model. Specifically, the
      ratio of T:C (TCR) was manipulated via hormone implants and injections and
      concentrations measured to evaluate the relative contribution of each hormone to
      skeletal muscle protein balance. Skeletal muscle growth was measured 16 days
      after gastrocnemius muscle ablation. Elevations in plasma concentrations of C
      (via daily C injections, 50 mg kg*kg(-1) body mass) resulted in TCR of 0.007 that
      was less than the control group TCR of 0.249. In this C-injected group, whole
      body and skeletal muscle atrophy was elicited-this being greater in the fast
      twitch plantaris muscle than in the slow-twitch soleus muscle. The overloaded leg
      resisted the C-induced atrophy. Castration of animals (TCR 0.024) resulted in
      less whole body and skeletal muscle growth. However, elevations in plasma
      concentrations of T (two groups, with TCR of 1.35 and 1.64) did not result in
      significantly greater muscle growth. Furthermore, T was also ineffective in
      antagonizing the C-induced atrophy in a group that received both T implants and C
      injections. This group had a TCR of 0.175 that was similar to the control group
      ratio of 0.249 that received no manipulations. We concluded that glucocorticoids
      were able to induce pronounced atrophy, but at the same time overloaded muscles
      were able to over-ride the glucocorticoid signal. Plasma concentrations of C were
      a better predictor of muscle growth/atrophy than T and/or the TCR. In addition,
      it is suggested that the volume of contractile activity of the muscle is perhaps
      an important determinant of C-induced atrophy, because less atrophy occurs in the
      more active slow twitch muscles.

PMID- 8861672
TI  - Work load during floor cleaning. The effect of cleaning methods and work
      technique.
AB  - Cardiovascular and muscle load levels were evaluated during floor cleaning. A
      group of 12 experienced female cleaners participated in the study. Of the
      subjects 6 used a mopping method and 6 a traditional scrub and cloth method.
      Heart rate, oxygen consumption, rating of perceived exertion, electromyography
      from the trapezius muscle and video recordings were obtained during floor
      cleaning. With respect to relative heart rate and oxygen consumption the two
      groups did not differ. The results revealed a high cardiovascular load
      corresponding on average to 53 percent of the individual maximal oxygen uptake.
      In addition 65 percent of the observed period was spent with the back in a
      position forward flexed more than 20 degrees C. The time spent in extreme forward
      back flexion was shorter for the mopping group. Both groups exhibited high
      static, median and peak shoulder muscle load levels of 10 percent, 25 percent and
      54 percent maximal voluntary contraction, respectively. At the same time,
      however, the mopping group tended to have a higher shoulder load than the group
      using the scrub and cloth method. Furthermore, electromyographic signs of fatigue
      in the trapezius muscle indicated a more stereotype activation of the shoulder
      muscles during mopping than during scrubbing. Based on these results, it was
      concluded that mopping cannot be recommended as less strenuous than scrubbing.

PMID- 8861673
TI  - Effect of acute mild hypoxia during exercise on plasma free and sulphoconjugated
      catecholamines.
AB  - Catecholamine (CA) response to hypoxic exercise has been investigated during
      severe hypoxia. However, altitude training is commonly performed during mild
      hypoxia at submaximal exercise intensities. In the present study we tested
      whether submaximal exercise during mild hypoxia compared to normoxia leads to a
      greater increase of plasma concentrations of CA and whether plasma concentration
      of catecholamine sulphates change in parallel with the CA response. A group of 14
      subjects [maximal oxygen uptake, 62.6 (SD 5.2) ml*min(-1)*kg(-1) body mass]
      performed two cycle ergometer tests of 1-h duration at the same absolute exercise
      intensities [191 (SD 6) W] during normoxia (NORM) and mild hypoxia (HYP) followed
      by 30 min of recovery during normoxia. Mean plasma concentrations of
      noradrenaline ([NA]), adrenaline ([A]), and noradrenaline sulphate ([NA-S]) were
      elevated (P <0.01) after HYP and NORM compared with mean resting values and were
      higher after HYP [20.9 (SEM 3.1), 2.2 (SEM 0.24), 8.12 (SEM 1.5) nmol . 1(-1),
      respectively] than after NORM [(13.7 (SEM 0.9), 1.5 (SEM 0.14), 6.8 (SEM 0.7)
      nmol . 1(-1), respectively P <0.01]. The higher plasma [NA-S] after HYP (P <0.05)
      were still measurable after 30 min of recovery. From our study it was concluded
      that exercise at the same absolute submaximal exercise intensity during mild
      hypoxia increased plasma CA to a higher extent than during normoxia. Plasma [NA
      S] response paralleled the plasma [NA] response at the end of exercise but, in
      contrast to plasma [NA], remained elevated until 30 min after exercise.

PMID- 8861674
TI  - Changes in lipid profile variables in response to submaximal and maximal exercise
      in trained cyclists.
AB  - This study examined the effect of prolonged submaximal exercise followed by a
      self-paced maximal performance test on cholesterol (T-Chol), triglycerides (TG),
      and high-density lipoprotein cholesterol (HDLC). Nine trained male athletes
      cycled at 70 percent of maximal oxygen consumption for 60 min, followed by a self
      paced maximal ride for 10 min. Venous blood samples were obtained at rest, at 30
      and 60 min during submaximal exercise, and immediately after the performance
      test. Lactic acid, haematocrit (Hct), haemoglobin (Hb), T-Chol and TG were
      measured in the blood, while plasma was assayed for HDL-C. Plasma volume changes
      in response to exercise were calculated from Hct and Hb values and all lipid
      measurements were corrected accordingly. In order to ascertain the repeatability
      of lipid responses to exercise, all subjects were re-tested under identical
      testing conditions and experimental protocols. When data obtained during the two
      exercise trials were analysed by two-way ANOVA no significant differences (P >
      0.05) between tests were observed. Consequently the data obtained during the two
      testing trials were pooled and analysed by one-way ANOVA. Blood lactic acid
      increased nonsignificantly (P > 0.05) during the prolonged submaximal test, but
      rose markedly (P <0.05) following the performance ride. Lipid variables
      ascertained at rest were within the normal range for healthy subjects. ANOVA
      showed that blood T-Chol and TG were unchanged (P > 0.05), whereas HDL-C rose
      significantly (P <0.05) in response to exercise. Post hoc analyses indicated that
      the latter change was due to a significant rise in HDL-C after the performance
      ride. It is concluded that apparent favourable changes in lipid profile variables
      occur in response to prolonged submaximal exercise followed by maximal effort,
      and these changes showed a good level of agreement over the two testing
      occasions.

PMID- 8861675
TI  - The effects of plasma cortisol elevation on total and differential leukocyte
      counts in response to heavy-resistance exercise.
AB  - The purpose of this study was to examine the impact of heavy-resistance exercise
      induced elevations of plasma cortisol on circulating leukocyte counts. Nine
      healthy, recreationally weight-trained men volunteered for this investigation.
      Two exercise protocols were employed. Protocol 1 (P-1) consisted of eight sets of
      ten-repetition maximum leg-press exercise with 1-min rest periods between sets.
      Protocol 2 (P-2) was identical except for 3-min rest periods. A non-exercise
      protocol was used as a control treatment (C). Venous blood samples, heart rates
      and ratings of perceived exertion were obtained pre-, mid- and 5 min post
      exercise. In order to examine the maximal influence of cortisol on leukocyte
      counts, we placed the subject's highest magnitude of cortisol change in response
      to one of the heavy-resistance exercise protocols in what we designated as the
      response protocol (R) and the other value was placed into what was designated as
      the non-response protocol (NR) for analysis. Significant increases in cortisol
      occurred from pre- to post-exercise for P-1 [mean (SD) 241.4 (25.0) to 302.0
      (60.0)nmol . 1(-1)] and in the R conditions pre- to mid- and pre- to post
      exercise [218.0(0.0) to 302.4 (37.1) to 326.8 (51.9)nmol . 1(-1)]. No significant
      changes in cortisol occurred for P-2, NR or the control conditions. Significant
      increases in total leukocyte counts occurred from pre- to mid- and pre- to post
      exercise both for R [5.6 (0.4) to 7.4 (0.3) to 7.3 (0.3) cells . 10(9) . 1(-1)]
      and NR [5.7 (0.3) to 6.9 (0.4) to 7.1(0.4) cells . 10(9) . l(-1)]. No significant
      changes in differential leukocyte counts occurred. In addition, no significant
      correlations between cortisol and total or differential leukocyte counts were
      observed. These data indicate that acute increases in total leukocytes along with
      no changes in differential leukocyte counts can occur in response to heavy
      resistance exercise that does not significantly elevate plasma cortisol
      concentrations.

PMID- 8861676
TI  - The prediction of power and efficiency during near-maximal rowing.
AB  - The relationship between power and gross efficiency during near-maximal rowing,
      and physiological measures of strength, power, aerobic and anaerobic capacities
      and United State Rowing Association (USRA) performance tests (independent
      variables) was investigated among collegiate male rowers. Criterion measures of
      rowing power and gross efficiency were measured in a moving-water rowing tank,
      using an oar instrumented with strain gauges to assess force and a potentiometer
      to assess oar position. Bivariate correlation analysis (n = 28) indicated no
      relationship between the independent variables and rowing gross efficiency (P >
      0.05). Rowing power [mean (SD) 483.4 (34.75) W] was significantly related to
      inboard leg extension strength (IL strength, r = 0.63), outboard leg extension
      strength (r = 0.45), combined leg extension strength (r = 0.45), and time to
      complete the USRA 2000-m simulated rowing race (r = -0.52; P <0.05). Stepwise
      regression using resampling cross-validation of 15 random samples (21 subjects
      per sample selected from a total group of 28 intercollegiate oarsmen) indicated
      that predictors of rowing power were IL strength and blood lactate following a
      peak oxygen uptake rowing test with significant multiple correlations of R 0.61
      to 0.86 (P <0.05). The standard error of estimate (SEM) ranged from 18.1 to 29.9
      W, or 5.3 (0.77) percent of the criterion value. Cross-validation with a hold-out
      group (seven subjects per sample) was performed for each equation and
      correlations ranged from R = 0.14 to 0.97 (SEM = 8.0 to 38.9 W). In conclusion,
      data from the present study suggest that to increase rowing power, training
      should emphasize leg strength and anaerobic training to decrease the level of
      lactate accumulated during rowing.

PMID- 8861677
TI  - The acute reversal of a diet-induced metabolic acidosis does not restore
      endurance capacity during high-intensity exercise in man.
AB  - The present experiment was designed to investigate whether a diet-induced
      metabolic acidosis was a major factor in the earlier onset of fatigue during high
      intensity exercise. Six healthy males cycled to exhaustion at a workload
      equivalent to 95 percent of maximum oxygen uptake on four separate occasions.
      Exercise tests were performed after an overnight fast and each test was preceded
      by one of four experimental conditions. Two experimental diets were designed,
      either to replicate each subject's own normal diet [N diet, mean (SD) daily
      energy intake (E) = 13 (0.7) MJ, 14.5 (0.8) percent protein (Pro), 37.5 (2.2)
      percent fat (Fat) and 47.5 (2.1) percent carbohydrate (CHO)], or a low
      carbohydrate diet [E = 12.6 (0.8) MJ, 33.6 (1.3) percent Pro, 64.4 (1.5) percent
      Fat and 2.2 (0.4) percent CHO]. These diets were prepared and consumed within the
      department over a 3-day period. Over a 3-period prior to the exercise trial
      subjects ingested either NaHCO(3) or CaCO(3) (3.6 and 3.0 mmol*kg body mass),
      thus giving four experimental conditions: N diet and treatment, N diet and
      placebo, low-CHO diet and treatment and low-CHO diet and placebo. Treatments were
      assigned using a randomised protocol. Arterialised venous blood samples were
      taken for the determination of acid-base status and metabolite concentrations at
      rest prior to exercise and at intervals for 30 min following exhaustion.
      Consumption of the low-CHO diet induced a mild metabolic acidosis which was
      reversed by the ingestion of NaHCO(3). Blood pH, bicarbonate (HCO-(3)) and base
      excess (BE) were higher following NaHCO(3) ingestion after the normal diet than
      all of the other experimental conditions (P <0.01). Exercise time following the
      low-CHO diet was less than on the normal diet conditions (P <0.05): bicarbonate
      ingestion had no effect on exercise time on either of the diet conditions. Post
      exercise blood pH, HCO-(3); and BE were higher following the ingestion of
      NaHCO(3) irrespective of the pre-exercise diet (P <0.05). Blood lactate
      concentration was higher 2 min after exercise following the N diet with NaHCO(3)
      when compared to the low-CHO diets with either NaHCO(3) or placebo (P <0.05).
      Plasma ammonia accumulation was not significantly different between experimental
      conditions. These data confirm previous data showing that the ingestion of a low
      CHO diet reduces the capacity to perform high-intensity exercise, but it appears
      that the metabolic acidosis induced by the low-CHO diet is not the cause of the
      reduced exercise capacity observed during high-intensity exercise under these
      conditions.

PMID- 8861678
TI  - Intravenous instrumentation alters the autonomic state in humans.
AB  - Intravascular instrumentation may induce syncope or presyncope. It is not known
      whether asymptomatic subjects also have autonomic reactions, albeit concealed. We
      addressed this issue by studying 44 healthy young male subjects of various levels
      of fitness, ranging from inactivity to athletic [mean maximal oxygen uptake was
      49.1 (SD 10.7) ml*kg(-1)*min(-1), range 28.7-71.9 ml*kg(-1)*min(-1)]. The
      autonomic response to venous cannulation was quantified by measuring heart rate
      before cannulation (HR(1)), after cannulation (HR(2)), and after complete
      pharmacological autonomic blockade (HR(0) = the intrinsic heart rate). The
      sympathovagal balance before and after cannulation was computed as HR(1)/HR(0)
      and HR(2)/HR(0), respectively. The group means of heart rate and sympathovagal
      balance decreased significantly (paired Student's t-test P <0.01) from 62.5 to
      59.9 beats*min(-1), and from 0.71 to 0.68, respectively. The maximal decrease in
      heart rate was 8.8 beats*min(-1), and in the sympathovagal balance was 0.11. Our
      study demonstrated that the asymptomatic subjects responded to intravenous
      instrumentation with a concealed autonomic reaction. Thus, from our findings it
      would seem that intravenous instrumentation interferes with measurements relating
      to autonomic nervous system activity.

PMID- 8861679
TI  - Threshold increases in plasma growth hormone in relation to plasma catecholamine
      and blood lactate concentrations during progressive exercise in endurance-trained
      athletes.
AB  - Plasma human growth hormone ([HGH]), adrenaline ([A]), noradrenaline ([NA]) and
      blood lactate ([La-](b)) concentrations were measured during progressive,
      multistage exercise on a cycle ergometer in 12 endurance-trained athletes [aged
      32.0 (SEM 2.0) years]. Exercise intensities (3 min each) were increased by 50 W
      until the subjects felt exhausted. Venous blood samples were taken after each
      intensity. The [HGH] and catecholamine concentrations increased negligibly during
      exercise of low to moderate intensities revealing an abrupt rise at the load
      corresponding to the lactate threshold ([La-]-T). Close correlations (P <0.001)
      were found between [La-]b and plasma [HGH] (r = 0.64), [A] (r = 0.71) and [NA] (r
      = 0.81). The mean threshold exercise intensities for [HGH], [A] and [NA],
      detected by log-log transformation, [154 (SEM 19) W, 162 (SEM 15) W and 160 (SEM
      17) W, respectively] were not significantly different from the [La-]-T [161 (SEM
      12) W]. The results indicated that the threshold rise in plasma [HGH] followed
      the patterns of plasma catecholamine and blood lactate accumulation during
      progressive exercise in the endurance-trained athletes.

PMID- 8861680
TI  - Effect of acute normobaric hypoxia on quadriceps integrated electromyogram and
      blood metabolites during incremental exercise to exhaustion.
AB  - This investigation analysed the effects of environmental hypoxia (EU) on changes
      in quadriceps integrated electromyogram (iEMG) and metabolite accumulation during
      incremental cycle ergometry. Trained male subjects (n = 14) were required to
      complete two maximal oxygen uptake (VO(2max)) tests, one test during EH (F(1)0(2)
      = 0.135), the other during normoxia (F(1)0(2) = 0.2093). The EMG were recorded at
      each exercise intensity from the vastus lateralis, rectus femoris and vastus
      medialis muscles over 60 cycle revolutions. Mean integral values were then
      calculated. Blood was collected from the radial vein of consenting subjects (n =
      8) at the end of each exercise intensity. Oxygen saturation of arterial blood
      (S(a)O(2)) was estimated using pulse oximetry. Gas exchange variables were
      collected on-line every 15 s. The results indicated that, without exception, EH
      significantly reduced total exercise time. Mean time to exhaustion in EH was
      26.34 (SD 2.58) min compared with 35.25 (SD 4.21) min during N. The S(a)O(2)
      values indicated that severe arterial desaturation had been achieved by EH. Mean
      values for VO(2max) obtained in EH were 49 ml*kg* min(-1), compared with 59
      ml*kg*min(-1) attained in N. Plasma lactate and ammonia concentrations were both
      significantly higher in EH. Increases in lactate and ammonia concentration were
      highly correlated in both N and EH. The onset of plasma lactate and ammonia
      accumulation occurred at the same exercise intensity in N. The iEMG responses of
      all three quadriceps muscles tended to be greater in the EH trials, although this
      difference was not significant. The basis for iEMG nonsignificance may have been
      related to large within sample variation in iEMG, sample size and the severity of
      the hypoxia induced.

PMID- 8861681
TI  - Effect of physical exercise on adoptive experimental auto-immune
      encephalomyelitis in rats.
AB  - The aim of the study was to determine whether different programmes of exercise
      influence adoptive monophasic experimental auto-immune encephalomyelitis
      (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced
      by the transfer of activated encephalitogenic T-lymphocytes into syngeneic
      recipients (Lewis rats, n = 85) and its development was followed by two
      independent observers. The results showed that 2 days of severe exercise (250 and
      300 min) performed after the adoptive transfer of EAE slightly delayed the onset
      of the disease (P <0.008) and the day of its maximal severity (P <0.016) without
      affecting the overall severity of the disease. When this programme of exercise
      was performed before the cell transfer, it had no effect (P > 0.05). Two more
      moderate exercise programmes (5 x 120 min of running at constant speed or 5 x 60
      min of running at variable speed, 5 consecutive days) performed between the
      adoptive transfer and the onset of the disease did not modify the development of
      the clinical signs of adoptive EAE (P >0.05). These results showed that severe
      exercise slightly influenced the effector phase of monophasic EAE and confirmed
      that physical exercise performed before the onset of experimental auto-immune
      diseases did not exacerbate the clinical signs.

PMID- 8861682
TI  - Effect of long-term intense swimming training on the upper body peak oxygen
      uptake of prepubertal girls.
AB  - The purpose of the present investigation was to determine the effect of a long
      term intense swimming programme on the aerobic potential of prepubertal girls.
      Five girls [GS, aged 9.3 (SD 0.5) years] participated in a 40-month intense
      training period. The girls trained on average 10-12 h*week(-1), approximately 1 h
      1.5 h twice a day, 5 days each week. Nine girls [CG aged 9.3 (SD 0.4) years] who
      were engaged in various activities (on average 1-4 h*week(-1)), but not in sports
      involving upper body muscle mass, served as the control group. All the children
      completed, on a special swim bench, an incremental maximal exercise prior to
      (pretest) and after (post-test) the swimming programme. Biometric parameters and
      the peak oxygen uptake (VO(2peak)) were determined using the same procedure at
      the pre- and post-test sessions. There was no significant difference between the
      two groups for any of the variables at the beginning of the study. The biometric
      characteristics remained similar at the post-test session, indicating that
      intense swimming training early in life has no influence on the physical growth
      of prepubertal children. The VO(2peak) expressed in absolute values, however,
      increased over a year in GS and CG by 38 percent and 13 percent, respectively.
      The improvement in CG VO(2peak) was related to normal growth and development
      while that of GS was much higher (P<0.01) than would have been expected due to
      growth factors alone. The reason for such an improvement could be attributed to
      an increase in the stroke volume and/or in the difference of the arteriovenous
      concentration of oxygen since the maximal O(2) pulse was different between CG and
      GS only at the post-test. Moreover, it increased after 10 months only in GS
      (delta maximal O(2) pulse: GS 1.09, P<0.01; CG 0.27 NS, ml.beat(-1)). Thus, the
      results of this study show that physiological adaptations can occur in
      prepubertal children as a consequence of intense physical training.

PMID- 8861683
TI  - Factors which alter the relationship between ventilation and carbon dioxide
      production during exercise in normal subjects.
AB  - The slope of the linear relationship between ventilation (V(E)) and carbon
      dioxide production (VC0(2)) has been thought to indicate that VC0(2) is one of
      the major stimuli to V(E). A group of 15 normal subjects undertook different
      incremental treadmill exercise protocols to explore the relationship between V(E)
      and VCO(2). An incremental protocol using 1 instead of 3-min stages of exercise
      resulted in an increase in the V E to VCO(2) ratio [26.84 (SEM 1.23) vs 31.08
      (SEM 1.36) (P <0.008) for the first stage, 25.24 (SEM 0.86) vs 27.83 (SEM 0.91)
      (P <0.005) for the second stage and 23.90 (SEM 0.86) vs 26.34 (SEM 0.81) (P =
      0.001) for the third stage]. Voluntary hyperventilation to double the control
      level of V(E) during exercise resulted in an increase in the V(E) to VCO(2) slope
      [from 21.3 (SEM 0.71) for the control run to 35.1 (SEM 1.2) for the
      hyperventilation run (P <0.001)]. Prolonged hyperventilation (5 min) during
      exercise at stage 2 of the Bruce protocol resulted in a continued elevation of
      VCO(2) and the V(E)/VCO(2) slope. A steady state of V(E) and metabolic gas
      exchange can only be said to have been present after at least 3 min of exercise.
      Voluntary hyperventilation increased the slope of the relationship between V(E)
      and VCO(2). End-tidal carbon dioxide fell, but remained within the normal range.
      These results would suggest that a non-carbon dioxide factor may have been
      responsible for the increase we found in V(E) during exercise, and that factors
      other than increased dead space ventilation can cause an increased ventilation to
      VCO(2) slope, such as that seen in some pathophysiological conditions, such as
      chronic heart failure.

PMID- 8861684
TI  - Co-activation and tension-regulating phenomena during isokinetic knee extension
      in sedentary and highly skilled humans.
AB  - The aim of this study was to examine isokinetic torque produced by highly skilled
      (HS) and sedentary (S) human subjects, during knee extension, during maximal
      voluntary and superimposed electrical activation. To verify the level of
      activation of agonist (vastus lateralis, VL, and vastus medialis, VM) and
      antagonist muscles (semi-tendineous, ST), during maximal voluntary activation,
      their myo-electrical activities were detected and quantified as root mean square
      (rms) amplitude. Ten HS and ten S subjects performed voluntary and superimposed
      isometric actions and isokinetic knee extensions at 14 angular velocities (from 
      120 to 300 degrees*s(-1)). The rms amplitude of each muscle was normalized with
      respect to its rms amplitude when acting as agonist at 15 degrees*s(-1). Whatever
      the angular velocity considered, peak torque and constant angular torque at 65
      degrees of HS were significantly higher (P <0.05) than those of S. Eccentric
      superimposed torque of S, but not HS, was significantly higher (P <0.05) than
      voluntary torque at -120, -90, - 60 and - 30 degrees*s(-1) angular velocities.
      For a given velocity, the rms amplitude of VL and VM were significantly lower (P
      <0.05), during eccentric than during concentric actions, in S, but not in HS.
      However, whatever the angular velocity, ST co-activation in HS was significantly
      lower (P < 0.05) than in S. We concluded that co-activation phenomenon could
      partly explain differences in isokinetic performances. Differences between
      voluntary and superimposed eccentric torques as well as lower agonist rms
      amplitude during eccentric action in S, support the possibility of the presence
      of a tension-regulating mechanism in sedentary subjects.

PMID- 8861685
TI  - Viscosity of the elbow flexor muscles during maximal eccentric and concentric
      actions.
AB  - The aim of the present study was to estimate the damping coefficient (B factor)
      of the elbow flexor muscles during both eccentric and concentric muscle actions.
      We used a muscle model consisting of a viscous damper associated in parallel with
      a contractile component, both in series with an elastic component. The viscous
      damper allowed the concentric loss and the eccentric gain of force to be
      modelled. Eight volunteer subjects performed maximal eccentric and concentric
      elbow movements on an isokinetic dynamometer at angular velocities of 0.52, 1.04
      and 2.09 rad*s(-1). Torques at an elbow joint angle of 90 degrees were recorded.
      Electromyogram (EMG) signals from the belly of the right elbow flexor and from
      the long head of the triceps brachia muscles were recorded using two pairs of
      bipolar surface electrodes. The root mean square (rms) of the EMG was determined.
      Eccentric and concentric rms were not significantly different (P >0.05). The B
      factor was higher in the concentric than in the eccentric conditions (P <0.05),
      and, whatever the muscle action type it decreased as the velocity increased.
      These results indicated that the concentric loss and the eccentric gain of force
      were attributable to the behaviour of the contractile machinery. Furthermore,
      whatever the exact cause of loss and gain of tension, our study showed that the
      total effect can be modelled by the viscous damper of a three-component muscle
      model.

PMID- 8861686
TI  - Effects of leg covering in humans on muscle activity and thermal responses in a
      cool environment.
AB  - Thermal responses and muscle performance in humans were studied during rest and
      exercise in a cool environment with different clothing distributions over the
      legs. Nine female subjects were exposed to 5 degrees C wearing shorts (SS),
      trousers with long legs (LL) or trousers with one long leg and one short leg (LS:
      LSc covered leg, LSu uncovered leg). The subjects also wore T-shirts and long
      sleeved shirts. The subjects were seated for 60 min and after this they performed
      light stepping exercise for a further 60 min. Rectal temperature (T(re)) and skin
      temperature from seven (LL, SS) or nine sites (LS) were measured continuously.
      Surface electromyography (EMG) from three muscles (biceps femoris, gastrocnemius
      and tibialis anterior) were recorded during the exercise from six subjects.
      Integrated EMG (iEMG) and mean power frequency (MPF) were used to describe muscle
      activity. The T(re) was virtually unchanged during rest in every ensemble,
      whereas during exercise T(re) was significantly lower in SS than in LL. Mean skin
      temperature (T(sk)) decreased during rest in every ensemble, being significantly
      lower in SS than in LL. After the rest period local T(sk) of thigh and calf were
      significantly lower in SS than in LL and they were also lower in LSu than in LSc.
      At the beginning of the exercise the iEMG of the tibialis anterior muscle in SS
      and LL averaged 84 (SEM 7) and 64 (SEM 3) mu V (P <0.05), respectively.
      Respective values for LSu and LSc were 86 (SEM 9) and 66 (SEM 6) mu V (P <0.05).
      The MPF of the tibialis anterior muscle was significantly higher in LL 102 (SEM
      5) Hz than in SS 90 (SEM 5) Hz (P <0.05) and similarly the MPF of the
      gastrocnemius muscle was also higher in LL 111 (SEM 5) Hz than in SS 100 (SEM 5)
      Hz (P < 0.05). It was concluded that exposing bare legs to a cool environment
      enhanced the motor unit activity in relation to covered legs. This would suggest
      that wearing shorts in a cool environment may, at the beginning of exercise,
      result in higher (about 25 percent) EMG activity and this may reflect increased
      muscle strain in comparison with wearing long trousers. Our results showing a
      unilateral increase in EMG activity during unilateral cooling suggest that the
      increase of strain is restricted to the uncovered part of the limb.

PMID- 8861687
TI  - Exercise training mode affects the hemodynamic responses to lower body negative
      pressure in women.
AB  - To determine if different exercise modes used to improve cardiovascular fitness
      result in differing cardiovascular responses to lower body negative pressure
      (LBNP) in exercise-trained women, seven chronically exercising female runners
      (RUN) and 11 swimmers (SWIM) of similar fitness levels maximal oxygen uptake,
      [VO(2max), mean (SEM) = 50 (2) and 45 (2) ml*kg(-1)*min(-1), respectively; P >
      0.05] underwent serial exposures to LBNP at pressures of 0, -1.3, -2.7 and -5.3
      kPa (referenced to ambient barometric pressure). Forearm vascular resistance
      (venous occlusion plethysmography) increased with LBNP but did not differ between
      groups at any level of LBNP. At 0 and - 1.3 kPa, the total peripheral resistance
      index (TPRI; impedance cardiography) was significantly (P <0.05) higher in RUN
      than SWIM [1.118(0.028) vs 0.787 (0.040) at 0 kPa and 1.245 (0.100) vs 0.840
      (0.040) 2 kPa*l* min(-1)*m(-2) at -1.3kPa]. At an LBNP of -2.7kPa, stroke index
      (SI) was significantly higher in SWIM than RUN [57.8(4.6) vs 41.9 (4.0) ml*beat(
      1)*m(-2)] while TPRI remained greater in RUN than SWIM. At -5.3 kPa, SWIM
      exhibited a higher cardiac index [3.232 (0.209) vs 2.447 (0.189) l*min(-1)*m(-2)]
      and SI [49.4 (4.4) vs 31.0 (4.5) ml *beat(-1)*m(-2)] but reduced heart rate
      [71(3) vs 83(5) beats . min(-1)] and TPRI [0.968 (0.043) vs 1.655 (0.128)
      kPa*1*min(-1)* m(-2)]. Mean arterial pressure declined significantly at an LBNP
      of -5.3 kPa in both groups; pulse pressure was lower (P <0.05) in RUN than SWIM
      at LBNP values of -2.7 and -5.3 kPa. These data suggest that: (1) female runners
      experience a greater increase in systemic vasoconstriction even though female
      swimmers can better maintain their cardiac index at high levels of LBNP, and (2)
      training mode appears to affect the pulse pressure responses to LBNP in exercise
      trained women.

PMID- 8861688
TI  - Effect of fatigue on maximal velocity and maximal torque during short exhausting
      cycling.
AB  - A group of 24 subjects performed on a cycle ergometer a fatigue test consisting
      of four successive all-out sprints against the same braking torque. The subjects
      were not allowed time to recover between sprints and consequently the test
      duration was shorter than 30 s. The pedal velocity was recorded every 10 ms from
      a disc fixed to the flywheel with 360 slots passing in front of a photo-electric
      cell linked to a microcomputer which processed the data. Taking into account the
      variation of kinetic energy of the ergometer flywheel, it was possible to
      determine the linear torque velocity relationship from data obtained during the
      all-out cycling exercise by computing torque and velocity from zero velocity to
      peak velocity according to a method proposed previously. The maximal theoretical
      velocity (v(0)) and the maximal theoretical torque (T(0)) were estimated by
      extrapolation of each torque-velocity relationship. Maximal power (P(max)) was
      calculated from the values of T(0) and v(0) (P(max) = 0.25v(0)T(0). The kinetics
      of v(0), T(0) and P(max) was assumed to express the effects of fatigue on the
      muscle contractile properties (maximal shortening velocity, maximal muscle
      strength and maximal power). Fatigue induced a parallel shift to the left of the
      torque-velocity relationships. The v( 0), T(0) and P(max) decreases were equal to
      16.3 percent, 17.3 percent and 31 percent, respectively. The magnitude of the
      decrease was similar for v(0) and T(0) which suggested that P max decreased
      because of a slowing of maximal shortening velocity as well as a loss in maximal
      muscle strength. However, the interpretation of a decrease in cycling v(0) which
      has the dimension of a maximal cycling frequency is made difficult by the
      possible interactions between the agonistic and the antagonistic muscles and
      could also be explained by a slowing of the muscle relaxation rate.

PMID- 8861689
TI  - Physical work capacity in dynamic exercise with differing muscle masses in
      healthy young and older men.
AB  - Ten young (aged 23-30 years) and nine older (aged 54-59 years) healthy men with
      similar estimated limb muscle volumes performed, in random order, three different
      types of ergometer exercise tests (one-arm cranking, two-arm cranking, and two
      leg cycling) up to the maximal level. Values for work load (WL), peak oxygen
      consumption (V0(2)), peak heart rate (HR), peak ventilation (V(E)), respiratory
      gas exchange ratio (R), recovery blood lactate concentration [La-], and rating of
      perceived exertion (RPE) were compared between the age-groups in the given
      exercise modes. No significant age-related differences in WL, peak V0(2), peak
      HR, R, [La-], or RPE were found in one-arm or two-arm cranking. During one-arm
      cranking the mean peak V0(2) was 1.65 (SD 0.26)1*min(-1) among the young men and
      1.63 (SD 0.10)l*min(-1) among the older men. Corresponding mean peak V0(2) during
      two-arm cranking was 2.19 (SD 0.32)1*min(-1) and 2.09 (SD 0.18)1*min(-1),
      respectively. During one-arm cranking peak V(E) was higher (P <0.05) among the
      older men compared to the young men. During two-leg cycling the young men showed
      higher values in WL (P <0.001), peak V0(2) (P <0.001), and peak HR (P <0.001).
      The mean peak V0(2) was 3.54 (SD 0.24)1*min(-1) among the young men and 3.02 (SD
      0.20)1 . min(-1) among the older men. Corresponding mean peak HR was 182 (SD 5)
      beats*min(-1) and 170 (SD 8) beats*min(-1), respectively. During two-leg cycling,
      peak V(E), R, [La-], and RPE did not differ between the two age-groups. In
      summary, the older men with similar sizes of estimated arm and leg muscle volumes
      as the young men had a reduced physical work capacity in two-leg cycling. In one
      arm or two-arm cranking, no significant difference in work capacity was found
      between the age-groups. These results indicate, that in healthy men, age, at
      least up to the 6th decade of life, is not necessarily associated with a decline
      in physical work capacity in exercises using relatively small muscle groups, in
      which the limiting factors are more peripheral than central.

PMID- 8861690
TI  - The effect of repeated muscle biopsy sampling on ATP and glycogen resynthesis
      following exercise in man.
AB  - The present study investigated the effect of repeated biopsy sampling on muscle
      adenosine 5'-triphosphate (ATP) and glycogen resynthesis following prolonged
      submaximal exercise. In one group of subjects (Ia, n = 7), biopsy specimens were
      obtained from the vastus lateralis immediately and 48 h after exhaustive one
      legged cycling from both the non-exercised (control) and exercised legs.
      Additional samples were obtained from the exercised leg at 3, 10 and 24 h post
      exercise. In a second group of subjects (Ib, n = 6), biopsy specimens were
      obtained immediately after exercise from both the control and exercised legs and
      at 48 h post-exercise from the exercised leg. All muscle biopsies were separated
      by a distance of 2.5 cm. In group Ia, ATP in the exercised leg was still lower
      after 48 h of recovery compared with the control leg (P <0.05), but complete
      restoration had occurred in group Ib (P > 0.05). Glycogen super compensation was
      not observed in group Ia. However, at the end of recovery, in group Ib glycogen
      in the exercised leg was 42 percent greater than in the control leg (P <0.01).
      Thus, following exhaustive dynamic exercise, repeated muscle biopsy sampling
      impaired ATP and glycogen resynthesis for several days, which may have been a
      result of the distance separating each biopsy site. The inhibition of ATP
      resynthesis appeared to be associated mainly with type II muscle fibres. The
      finding that, in contrast to muscle glycogen, ATP did not return to the basal
      level during the 48 h of recovery, suggests that the measurement of ATP may be a
      more sensitive measure of muscle damage than that of glycogen.

PMID- 8861691
TI  - Ultrasound of the abdomen in endurance athletes.
AB  - This project evaluated, if athletes show adaption of their abdominal organs in
      response to endurance training. Abdominal sonography was performed in 26
      sedentary male subjects [CO; age: 26 (SD 5) years; mass (BM): 78.7 (SD 10.6) kg;
      lean body mass [LBM): 67.1 (SD 7.4) kg; height (HE): 183 (SD 6) cm, individual
      anaerobic threshold (cycle ergometry; IAT): 2.1 (SD 0.1) W*kg(-1)], 14 moderately
      endurance trained athletes [EA1; age: 27 (SD 4) years; BM: 74.0 (SD 5.9) kg; LBM:
      64.6 (SD 4.5) kg; HE: 178 (SD 5) cm, IAT: 3.0 (SD 0.5) W*kg(-1)] and 27 well
      endurance trained athletes [EA2; age: 27 (SD 4) years; BM: 72.1 (SD 4.3) kg; LBM:
      65.4 (SD 3.2) kg; HE: 179 (SD 4) cm, IAT: 3.7 (SD 0.4) W*kg(-1)]. One subject of
      EA2 had cholecystolithiasis and another one renal redoublication. 3 persons
      showed uncomplicated parapelvine or subcapsular renal cysts (CO, EA1). The
      transverse area of the large abdominal arteries (abdominal aorta, common iliac
      arteries) was significantly greater in EA2 than in both EA1 and CO and partly
      greater in EA1 than in CO. Also, the ratios of sagittal and transverse diameters
      of the left and right lobes of the liver to LBM showed higher values for EA2 than
      for both EA1 and CO. These results indicate morphological adaptive processes of
      the great abdominal arteries in endurance athletes.

PMID- 8861692
TI  - Osteoplastic frontal sinusotomy and extradural microsurgical repair of
      frontobasal cerebrospinal fluid fistulas.
AB  - The choice of the surgical approach and operative technique for the management of
      cerebrospinal fluid (CSF) fistulas of the anterior cranial fossa are still a
      controversially discussed topic. Although "extracranial" approaches through the
      paranasal sinuses are becoming increasingly more popular among otolaryngologists
      and maxillo-facial surgeons, most neurosurgeons traditionally prefer the
      "intracranial" repair of CSF fistulas by a craniotomy. We present an approach
      through the frontal sinus for the repair of dural defects behind the posterior
      wall of the frontal sinus and at the floor of the anterior cranial fossa. The
      operative procedure comprises the following main steps: 1) exposure of the
      anterior wall of the frontal sinus by a bicoronal incision; 2) excision of the
      anterior wall without frontal burr holes; 3) bilateral removal of the posterior
      wall of the frontal sinus; 4) extradural inspection of the dura behind the
      frontal sinus and above the cribriform plate, ethmoidal roof, and orbital roof
      bilaterally; 5) closure of dural tears by direct suture and a periosteal graft;
      6) reinsertion of the anterior wall of the frontal sinus and fixation with
      titanium micro plates. Twenty-five patients operated upon using this technique
      are described. The aetiology of the frontobasal lesion was traumatic in 23, and
      an ethmoid carcinoma in two. In all patients, the dural fistulas were
      successfully repaired during the initial procedure. One patient died from sudden
      circulatory arrest after an uneventful postoperative course of nine days.
      Otherwise, there were no postoperative complications. This technique affords
      atraumatic extradural inspection and repair of dural fistulas bilaterally behind
      the frontal sinus, and above the cribriform plate and the ethmoidal and orbital
      roofs with none or minimal brain retraction. It therefore allows early repair of
      CSF fistulas also in patients with severe brain injury. Although we consider the
      extradural closure of fistulas the method of choice, this approach also allows
      for a combined extradural-intradural procedure, thus enabling the surgeon to
      treat associated intradural pathologies, such as traumatic lesions or tumours of
      the frontal cranial base.

PMID- 8861693
TI  - The orbitozygomatic infratemporal fossa approach: a quantitative anatomical
      study.
AB  - Using detailed cadaveric dissections this study has demonstrated and quantified
      the increase in exposure and additional access gained by using the
      orbitozygomatic infratemporal fossa approach for neurosurgical access. The
      surgical window of exposure can be increased by up to 300% when this technique is
      utilised to facilitate access via either a subtemporal (to access the P2 segment
      of the posterior cerebral artery) or transsylvian (to access the basilar
      bifurcation) approach. In addition the distance between the surgeon and the
      operative field can be decreased by approximately 2-3 cm. The orbitozygomatic
      infratemporal fossa approach is a relatively simple technique which can readily
      increase neurosurgical exposure of the skull base. It also provides simultaneous
      access to the infratemporal fossa, pterygopalatine fossa and the orbit.

PMID- 8861694
TI  - CO(2) and indomethacin vasoreactivity in patients with head injury.
AB  - The purpose of this study was to compare the effect of hyperventilation and
      indomethacin on cerebral circulation, metabolism and pressures in patients with
      acute severe head injury in order to see if indomethacin may act supplementary to
      hyperventilation. Fourteen severely head injured patients entered the study.
      Intracranial pressure (ICP), mean arterial blood pressure (MABP) and cerebral
      perfusion pressure (CPP) were monitored continuously. Within the first four days
      after the trauma the CO(2) and indomethacin vasoreactivities were studied by
      measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous (133)Xe
      technique) and arterio-venous difference of oxygen (AVdO(2)). Ischaemia was
      evaluated from changes in CBF, saturation of oxygen in the jugular bulb
      (SvjO(2)), lactate and lactate/oxygen index (LOI). Data are presented as medians
      and ranges, results are significant unless otherwise indicated. Before
      intervention ICP was well controlled ,(14.8 (9-24) mmHg) and basic CBF level was
      39.1 (21.6-75.0) ml/100 g/min). The arterio-venous oxygen differences were
      generally decreased (AVdO(2) = 4.3 (1.8-8.1) ml/100 ml) indicating moderate
      luxury perfusion. Levels of CMRO(2) were decreased (1.54 (0.7-3.2) ml/100 g/min)
      as well. During hyperventilation (delta PaCO(2)=0.88 (0.62-1.55) kPa) CBF
      decreased with 11.8 (-33.4-29.7) %/kPa and ICP decreased with 3.8 (0-10) mmHg.
      AVdO(2) increased 34.0 (4.0-139.2) %/kPa, MABP was unchanged, CMRO(2) and CPP
      increased (delta CPP = 3.9 (-10-20) mmHg). AVD (lactate) and LOI were unchanged.
      No correlations between CBF responses to hypocapnia and outcomes were observed.
      An i.v. bolus dose of indomethacin (30 mg) decreased CBF 14.7 (-16.7-57.4)% and
      ICP decreased 4.3 (-1-17) mmHg. AVdO(2) increased 27.8 (-40.0-66.7)%, MABP (delta
      MABP = 4.9 (-2-21) mmHg) and CPP (delta CPP = 8.7 (3-29) mmHg) increased while
      CMRO2 was unchanged. No changes in AVd (lactate) and LOI indicating cerebral
      ischaemia were found. Compared to hyperventilation (changes per 1 kPa, at PaCO(2)
      level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater
      after indomethacin, while the changes in AVdO(2), ICP, SvjO(2) and LOI were of
      the same order of magnitude. No correlation between relative reactivities to
      indomethacin and CO(2), evaluated from changes in CBF and AVdO(2), or between the
      decrease in ICP after the two procedures were found. Thus, some patients reacted
      to indomethacin but not to hyperventilation, and vice versa. These results
      suggest that indomethacin and hyperventilation might act independently, or in a
      complementary fashion in the treatment of patients with severe head injury.

PMID- 8861696
TI  - Primary central nervous system lymphoma: variety of clinical manifestations and
      survival.
AB  - A retrospective analysis of 23 non-immune compromised patients with primary
      central nervous system lymphoma (PCNSL) is reported. The patients consist of 14
      males and 9 females and the median age is 50 years. Most patients presented with
      focal neurological deficits or symptoms of increased intracranial pressure (ICP)
      due to mass effects around the periventricular area. However, there were four
      cases of diffuse type, one case of intramedullary tumour, and four cases with
      rapid disease progression. All the patients underwent histological confirmation
      by craniotomy (16 cases) or stereotactic biopsy (7 cases). The radiation therapy
      started after histological diagnosis in all and 6 cases received additional
      chemotherapy. The median survival after diagnosis of overall patients was 23
      months. Six patients are in disease free status at a mean of 35 months follow-up.
      The uni- and multi-variative risk analysis revealed five favourable factors on
      survival: (1) age less than 60 years (0.05 < p < 0.1); (2)pre-operative Karnofsky
      performance scale (KPS) > or = 70 (p < 0.05); (3) symptom duration over four
      weeks (p < 0.05); (4) radiation dosage > or = 5500 cGy (p < 0.05); (5)absence of
      malignant cells in cerebrospinal fluid (CSF) (p < 0.05). The most frequent site
      of recurrence was the local area as shown in seven cases out of 11 recurrent
      cases. But six patients had diffuse recurrence (4 cases), systemic recurrence (2
      cases), and drop metastasis (1 case). Although the recurred PCNSL had rapid
      progression and a grave prognosis, aggressive treatment prolonged the
      postrecurrence survival time significantly. Our experience suggests that 1) there
      are various clinical and radiological presentations and progressions of the
      disease; 2) treatment method should be decided along with the clinical
      presentation, progression of disease, and prognostic factors; 3) early diagnosis
      and early detection of recurrence enable the start of definitive treatment when
      the medical condition is still satisfactory.

PMID- 8861695
TI  - Peri-operative prophylaxis with phenytoin: dosage and therapeutic plasma levels.
AB  - Early postoperative epilepsy is a frequent complication of supratentorial
      intracranial surgery. The lack of consensus on prophylaxis of early postoperative
      seizures with phenytoin (PHT) may be due to the different dosages used in several
      studies, owing to inadequate therapeutic plasma level. The aim of this study was
      to evaluate which dosage of PHT can maintain the therapeutic range in the early
      postoperative period. Twenty patients operated on for supratentorial neoplasms
      were randomly allocated to receive, during the last hour of the surgical
      procedure, loading doses of either 10 mg/kg (group A, n = 10) or 15 mg/kg (group
      B, n = 10) of PHT. PHT infusion rate never exceeded 30 mg/min. Six hours after
      the loading dose, PHT maintenance treatment (250 mg, i.v., every 8 hours) was
      started in all patients. PHT plasma levels were evaluated from the end of the
      intra-operative loading infusion up to 24 h. During the first six hours after the
      loading dose, phenytoin plasma levels fell below the therapeutic range (10-20
      mg/l) in 7 out of the 10 patients receiving 10 mg/kg, while in the patients
      treated with 15 mg/kg, PHT plasma levels were always in the therapeutic range (P
      < or = 0.0001). PHT maintenance dose was sufficient to keep plasma levels within
      the therapeutic range in 8 patients in group A, and in all the patients in group
      B. It is concluded that a loading dose of 15 mg/kg, followed by postoperative
      treatment, is necessary to guarantee therapeutic plasma levels of phenytoin in
      the immediate postoperative period, when seizure risk is very high.

PMID- 8861697
TI  - Synthesized surface anatomy scanning (SSAS) for surgical planning of brain
      metastasis at the sensorimotor region: initial experience with 5 patients.
AB  - Surface anatomy scanning (SAS) is a powerful technique that uses T2-weighted
      magnetic resonance images (MRI) to visualize brain surface structures, and to
      precisely localize subcortical lesions. To overcome technical limitations of this
      method, synthesized SAS (SSAS) superimposes MR angiography (MRA) data on the SAS
      images. We describe our initial experience with surgical planning for the
      resection of metastases at the sensorimotor region in 5 patients using SSAS.
      Neurological deficits were assessed before and after surgical resection. Although
      4 of 5 patients had mild to severe neurological deficits before surgery, three
      became symptom-free and no patient had an increased deficit after surgery. Our
      results undoubtedly provide palliative surgery for sensorimotor metastases. As
      SSAS is non-invasive and requires a short scanning time, this method could become
      a useful technique for the routine pre-operative simulation for surgery on brain
      surface lesions such as sensorimotor metastases.

PMID- 8861698
TI  - Embolization of cerebral aneurysms with a liquid embolus, EVAL mixture: report of
      three cases.
AB  - Embolization of three surgically difficult cerebral aneurysms was performed using
      our newly developed non-adhesive embolic material, EVAL mixture (ethylene vinyl
      alcohol copolymer). Conventional embolic materials such as detachable balloons or
      microcoils were not used because of a large or irregular aneurysmal neck. After
      temporary occlusion of the parent artery with a superselective balloon catheter,
      the EVAL mixture was slowly injected through a microcatheter placed in the
      aneurysm or parent artery. The locations of the aneurysms were anterior
      communicating artery, basilar artery-posterior cerebral artery and basilar artery
      anterior inferior cerebellar artery (BA-AICA). One aneurysmal occlusion and 2
      parent artery occlusions were performed. Patients had no persistent deficits. The
      patient with the BA-AICA aneurysm associated with an arteriovenous malformation
      died of rupture of the residual AVM due to haemodynamic change 2 weeks after
      embolization. In selected and limited cases, embolization of surgically difficult
      cerebral aneurysms using EVAL mixture was more effective and safer than
      embolization using conventional embolic materials such as balloons and
      microcoils.

PMID- 8861699
TI  - SPECT with technetium-99m-HMPAO in relation to late cognitive outcome after
      surgery for ruptured cerebral aneurysms.
AB  - Fifteen patients with a good neurological outcome after aneurysmal SAH and
      surgery were collected prospectively. Six months after surgery neurological
      examination and a SPECT study for evaluation of the three dimensional CBF
      distribution as well as an extensive neuropsychological test were performed. In
      all patients with pathological SPECT findings the location of the reduced
      regional CBF correlated with the location of the ruptured aneurysm and/or side of
      surgical approach. The volume of the brain tissue with reduced rCBF showed a
      great variety, from 9-112 cm(3) (mean: 33 cm(3)). Similarly, the maximum flow
      reduction in the affected areas also varied considerably from 17-95% (mean: 39%).
      In general, the neuropsychological functioning of the patients post SAH was
      favourable. Seven individuals had a presumably normal neuropsychological
      appearance with respect to estimates of premorbid levels of functioning. Another
      four patients were slightly impaired and the remaining four were moderately
      affected. Only in five cases did the location of SPECT pathology and the site of
      neuropsychological impairment appear to coincide, whereas this was not the case
      in the remaining 10 patients. In general, the extent of SPECT pathology did not
      differ in the three neuropsychological outcome groups (normal, slight and
      moderate disability).

PMID- 8861700
TI  - Entrapment neuropathy at the cubital tunnel: simple decompression is the method
      of choice.
AB  - We present a retrospective study of 41 patients treated by simple decompression
      for ulnar neuropathy. Pre- and postoperatively, patients were evaluated
      clinically and electrophysiologically. The median follow-up was 2 years (minimum:
      0.5 years, maximum: 5.1 years). The leading pre-operative sign was motor loss in
      the ulnar distribution (36 patients = 89%) with consecutive atrophy of ulnar
      innervated muscles (30 patients = 75%). The secondary complaint was sensory
      impairment in 59% of all cases, less frequently patients presented with pain or
      paraesthesia. In the majority of cases the aetiology remained unknown (27
      patients = 65%). When aetiology was known, previous trauma to the elbow was
      reported most frequently (9 patients = 22%). Motor nerve conduction velocity
      (mNCV), compared to the contralateral, non-involved arm, was lower at least for
      10 m/s. In cases with atrophy of the ulnar innervated muscles the difference was
      greater than 15 m/s. In 89%, postoperative results were good or even very good.
      In 8% (3 patients) no improvement was observed. Worsening due to surgery did not
      occur. We could demonstrate a significant increase in postoperative mNCV of 7.95
      m/s in all patients (p < 0.05). There is still disagreement as to the correct
      surgical treatment of this disorder. We favour simple decompression (SD) as the
      appropriate operative technique for cubital tunnel syndrome.

PMID- 8861701
TI  - Posterolateral decompression and stabilization of thoracolumbar injuries using
      Diapason instrumentation.
AB  - The authors describe a series of 28 patients with thoracolumbar spine injury who
      were decompressed via a posterolateral approach and stabilized with a new
      material for osteosynthesis called Diapason. Similarly to other osteosynthesis
      systems, it combines the advantages of pedicular fixation and rod stabilization.
      All patients were studied pre- and postoperative by plain X-ray films, standard
      and 3-D CT scan. The sagittal index (S.I.) was calculated in all patients to
      quantify segmental sagittal deformity. Patient follow-up ranged from 1 to 3
      years. Twenty-two patients who presented with neurological deficit improved
      (78.5%). Twenty-six patients (92.8%) developed osseous union and 5 patients with
      spinal deformity (S.I. > 15 degrees) presented a postoperative S.I. of less than
      5 degrees at long-term check-up; S.I. underwent a current of 2 degrees in one
      patient only but it remained stable at subsequent controls. Instrument failure
      occurred in 4 cases (screw breakage in 1 case, rod displacement in 3) but only
      one required reoperation because the others were asymptomatic and presented solid
      fusions.

PMID- 8861702
TI  - Correlation between spinal cord blood flow and arterial diameter following acute
      spinal cord injury in rats.
AB  - Simultaneous measurements of spinal cord blood flow and arterial diameter at
      areas adjacent to a site of spinal cord injury were carried out to determine
      changes in CO(2) reactivity and autoregulation. The spinal cord injury was made
      at T10 level by the epidural clip compression method. A spinal window was drilled
      at an area either 7 mm caudal or 7 mm rostral to the injury site for the
      measurement of spinal cord blood flow and arterial diameter at the same time.
      Spinal cord blood flow was decreased at both spinal windows, especially at the
      rostral window. Arterial diameter was also decreased significantly at both sites.
      The ischaemic zone evaluated histologically tended to expand more diffusely in
      the rostral direction than in the caudal direction. In the pre-injury stage, both
      CO(2) reactivity and autoregulation were present in the spinal cord. Following
      the clip injury, CO(2) reactivity and autoregulation were both impaired in the
      areas 7 mm adjacent to the impact site. Correlation coefficients suggested that
      the rostral spinal cord tended to sustain more injury than the caudal spinal
      cord. The histologically proven spinal cord ischaemia following the injury may
      have resulted from the decreased arterial diameter and impaired CO(2) reactivity
      and dysautoregulation of the spinal cord.

PMID- 8861703
TI  - Vasodilation by intrathecal lipopolysaccharide of the cerebral arteries after
      subarachnoid haemorrhage in dogs.
AB  - To investigate the influence of inducible nitric oxide synthase on cerebral
      arteries after subarachnoid haemorrhage (SAH) in vivo, lipopolysaccharide (LPS),
      a major inducer of inducible nitric oxide synthase, was injected intracisternally
      into control and SAH model dogs. Intracisternal injection of LPS (0.5 mg)
      produced a long-lasting, submaximal vasodilation of the basilar artery of control
      dogs on angiography. This effect became significant at 4 hours after LPS
      injection and plateaued after 6 hours. This vasodilation was reduced by N(G)
      monomethyl-L-arginine. Vasopressin slightly suppressed the vasodilation, while
      bradykinin increased it. The concentration of L-arginine in CSF decreased after
      LPS injection, while that of L-citrulline increased. In cytokines, the
      concentration of tumour necrosis factor-alpha; (TNF-alpha;) in CSF increased
      transiently at 4 hours after LPS injection, while interleukin-1 beta, interleukin
      6, interferon-gamma, did not change. These data suggest that vasodilation by LPS
      is mainly due to nitric oxide predominantly synthesized by an inducible nitric
      oxide synthase, proximally induced by TNF-alpha. Our data make it unlikely that
      SAH itself induces the inducible nitric oxide synthase in vascular tissue, since
      isolated endothelium-denuded basilar artery from SAH model dogs did not respond
      to L-arginine. In SAH model dogs, the degree of vasodilation by LPS differed with
      the severity of vasospasm. Vasodilation was much greater in mild than in severe
      vasospasm in dogs, and was increased by superoxide dismutase. These findings
      suggest that the induction of inducible nitric oxide synthase or its activity may
      be less effective in severe vasospasm.

PMID- 8861705
TI  - Ablation of neural tissue by short-pulsed lasers--a technical report.
AB  - The basis for most laser applications in neurosurgery is the conversion of laser
      light into heat when the incident laser beam is absorbed by the tissue.
      Irradiation of neural tissue with laser light therefore leads to its thermal
      damage. However, due to the diffusion of heat energy into the surrounding tissue,
      often there is thermal damage to neural tissue outside the area of the target
      volume. These are the characteristics of thermal laser/tissue interaction. In
      this paper we discuss how we used three different short-pulsed lasers to achieve
      non-thermal ablation of neural tissue. Three different short-pulsed lasers were
      used to generate ultrashort laser pulses in the picosecond to femtosecond range.
      The interaction of such laser pulses with tissue was predicted to be nonthermal.
      The short-pulsed lasers were used for the ablation of neural tissue using an in
      vitro calf brain model. The histopathological examination of the lesions revealed
      that the neural tissue had been removed very precisely without any sign of
      thermal damage to the surrounding tissue.

PMID- 8861704
TI  - The effects of the pretreatment of intravenous high dose methylprednisolone on
      Na(+)-K(+)/Mg(+2) ATPase and lipid peroxidation and early ultrastructural
      findings following middle cerebral artery occlusion in the rat.
AB  - The sodium-potassium activated and magnesium dependent adenosine-5'
      triphosphatase (Na(+)-K(+)/Mg(+2) ATPase EC.3.6.1.3.) activity and lipid
      peroxidation and early ultrastructural findings were determined in rat brain at
      the acute stage of ischaemia produced by permanent unilateral occlusion of the
      middle cerebral artery (MCA). The effects of the pretreatment with intravenous
      high-dose methylprednisolone (MP) on these biochemical indices and
      ultrastructural findings were also evaluated in the same model. The rats were
      divided into four groups. In group I, 10 rats were used to determine Na(+)
      K(+)/Mg(+2) ATPase activity and the extent of lipid peroxidation by measuring the
      malondialdehyde (MDA) content and normal ultrastructural findings. In group II on
      20 rats, only subtemporal craniectomy was done in order to determine the effects
      of the surgical procedure on these indices and findings. This group was treated
      intravenously with saline solution before occlusion. In group III with MCA
      occlusion, saline solution was administered intravenously to 20 rats in the same
      amount of methylprednisolone used in group IV, ten minutes before the occlusion.
      In Group IV, a single high-dose (30 mg/kg) of methylprednisolone was administered
      intravenously, ten minutes before occlusion in 20 rats. After occlusion of the
      middle cerebral artery, Na(+)-K(+)/Mg(+2) ATPase activity was decreased promptly
      in the first ten minutes in the ischaemic hemisphere and remained at a lower
      level than the contralateral hemispheres in the same group and the normal levels
      in group I, during 120 minutes of ischaemia. A single dose methylprednisolone
      pretreatment prohibited the inactivation of Na(+)-K(+)/Mg(+2) ATPase. On the
      other hand, there was significant difference in malondialdehyde content between
      group I and group III. Malondialdehyde levels were significantly increased
      following ischaemia and a non-significant increase was observed in the
      contralateral hemisphere. Methylprednisolone treatment significantly decreased
      malondialdehyde content on the side of the ischaemic hemisphere. We conclude that
      there is a positive relationship between membrane-bound enzyme Na(+)-K(+)/Mg(+2)
      ATPase activity, malondialdehyde content and early ultrastructural changes in the
      treated group with MP. These data suggest that the pretreatment injection of high
      doses (30 mg/kg) methylprednisolone contribute to the protection of the brain
      from ischaemia with stabilization of the cell membrane by effecting the lipid
      peroxidation and the activation of Na(+)-K(+)/Mg(+2) ATPase.

PMID- 8861706
TI  - The long history of a cerebello-pontine angle epidermoid tumour--a case report
      and lessons learned.
AB  - The authors present the case of a patient accurately diagnosed and operated on
      for an epidermoid cyst in the CPA region, 30 years after the clinical onset with
      the initial symptom of hypoacusis. At the time of the operation, the patient
      presented with advanced CPA syndrome, and the tumour had grown to an enormous
      size. Complete capsule removal was not attempted due to its tenacious adherence
      to vital neurovascular structures. Thirteen years after surgery, the patient
      underwent a second operation due to tumour regrowth. The case provides supporting
      evidence that the clinical findings of a CPA epidermoid cyst may be minimal, and
      remain so for extended periods of time until the tumour has spread widely.
      Epidermoids tend to insinuate in the cisterns around cranial nerves, blood
      vessels, and the brainstem, rather than compressing these structures. The
      importance of early detection and radical removal, presently facilitated by
      Magnetic Resonance Imaging, is emphasized.

PMID- 8861707
TI  - Effects of calcium channel blockers on impairment of brain function in senescence
      accelerated mice.
AB  - The effects of the L-type calcium channel blockers, nicardipine, nimodipine,
      nilvadipine and amlodipine, on brain dysfunction were examined in senescence
      accelerated-prone mice. A disturbed brain function in passive avoidance response,
      forced swimming, rota-rod and traction tests was observed in senescence
      accelerated-prone mice compared to senescence-accelerated-resistant mice. A
      single oral administration of the four calcium channel blockers tested had little
      effect on the brain dysfunction in senescence-accelerated-prone mice. In
      contrast, the daily oral administration of nicardipine (1 and 3 mg/kg),
      nimodipine (3 mg/kg) and nilvadipine (3 mg/kg), once a day for three weeks,
      prolonged the shortened latency of step-through in the passive avoidance response
      and falling time in rota-rod tests. Brain dysfunction in forced swimming and
      traction tests was not influenced by repeated administration of these blockers.
      Repeated administration of amlodipine for three weeks in senescence-accelerated
      prone mice showed little pharmacological actions in all four tests. Thus, we
      found that repeated administration of nicardipine, nimodipine and nilvadipine
      ameliorated the brain dysfunction in these mice. Furthermore, the present study
      suggests that senescence-accelerated-prone mice can be used as an appropriate
      model for evaluating the pharmacological effects of calcium channel blockers on
      brain dysfunction.

PMID- 8861708
TI  - Dilazep inhibits binding of batrachotoxin to sodium channels in canine
      sarcolemmal vesicles.
AB  - We studied the effect of dilazep on the binding of [3H]- batrachotoxinin A 20
      alpha-benzoate ([3H]BTXB), which binds to and stabilizes the activated state of
      the Na+ channel, and compared it with that of lidocaine in canine cardiac
      sarcolemmal vesicles. Dilazep inhibited the specific [3H]BTXB binding in a dose
      dependent manner with an IC50 value of 0.37 microM, while lidocaine inhibited it
      with an IC50 value of 92 microM. Scatchard analysis of [3H]BTXB binding
      demonstrated that both dilazep and lidocaine reduced the amax without a marked
      effect on the K(D). The inhibition of [3H]BTXB induced by dilazep was reversible.
      Both dilazep (4 microM) and lidocaine (100 microM) increased the dissociation
      rate constant of [3H]BTXB only in concentrations which are about a 10-fold
      greater than their IC50, indicating the low affinity of both drugs for the
      [3H]BTXB-bound Na+ channel. However, dilazep (0.5 microM) and lidocaine (100
      microM) decreased significantly the association rate constant of the [3H]BTXB
      binding at concentrations near their IC50, indicating that the affinity of both
      drugs for the [3H]BTXB-unbound Na+ channel is relatively high. These results
      suggest that, in canine cardiac membrane vesicles, the effect of dilazep in
      inhibiting the binding of [3H]BTXB and stabilizing the Na+ channel is similar to
      that of lidocaine, but the potency of dilazep is greater than that of lidocaine.

PMID- 8861709
TI  - Voltage- and frequency-dependent modulation of L-type Ca2+ channel by MPC-1304, a
      novel calcium antagonist in guinea-pig hearts.
AB  - The electrophysiological effects of MPC-1304, a novel calcium antagonist, were
      examined using the conventional microelectrode and whole-cell patch-clamp
      techniques in guinea-pig hearts. MPC-1304, at 100 nM or higher concentrations,
      produced a dose-dependent reduction in the action potential duration of guinea
      pig papillary muscles, without changes in resting membrane potentials and maximum
      rate of rise of action potentials. In guinea-pig ventricular myocytes, MPC-1304
      (1-100 nM) dose-dependently depressed the initial inward currents induced by
      depolarizing pulses from a holding potential of -30 mV in the external Tyrode
      solution, as did nifedipine, whereas the late outward current was not changed by
      MPC-1304. In the presence of 100 nM of MPC-1304 or 100 nM of nifedipine, the
      first depolarizing pulse from a holding potential of -80 mV caused a depression
      of the isolated L-type Ca2+ current (I(Ca)) by 29.5 % and 29.4 % of the control,
      respectively (tonic block), and successive pulses further suppressed I(Ca) in a
      use-dependent manner (use-dependent block). The degree of steady state use
      dependent block of I(Ca) by 100 nM of MPC-1304 was 25.5 % at the stimulus
      frequency of 1 Hz and further increased to 34.0 % at 2 Hz (frequency-dependent
      block), which were significantly larger than those by 100 nM of nifedipine at
      both frequencies. The onset rate of use-dependent block by 100 nM MPC-1304 was
      significantly smaller than that by 100 nM nifedipine. MPC-1304 (100 nM) and
      nifedipine (100 nM) shifted the steady state inactivation curve of I(Ca) toward
      the negative potential by 3.3 mV and 9.1 mV in the mid-potential of the curve,
      respectively. The estimated dissociation constants of MPC-1304 were 137.7 and
      49.9 nM for the resting and inactivated states of the L-type Ca2+ channel,
      respectively, and those of nifedipine were 113.9 and 18.1 nM, respectively. We
      conclude that MPC-1304 suppress the L-type Ca2+ channel with slow kinetics in a
      voltage- and frequency-dependent manner, which might be caused by its high
      affinity to the activated as well as to the inactivated state of the channel.

PMID- 8861710
TI  - Drug profile of new benzofurane derivatives in guinea-pig isolated heart muscle
      preparations.
AB  - The recently synthesized benzofuranylethanolamines GE 68, GE 70, GE 76, RG 16 and
      RG 25, were studied in guinea-pig isolated papillary muscles and right atria.
      With regard to their inotropic, chronotropic and beta-adrenoceptor-blocking
      activity, these compounds were compared with the reference drug propafenone. GE
      68, GE 70 and GE 76 were almost equally potent as propafenone in reducing the
      isometric force of contraction of papillary muscles, while RG 16 and RG 25 were
      less effective than the parent drug. GE 70 decreased the spontaneous rate of
      activity of right atria in a similar concentration range as propafenone, whereas
      GE 68 showed a more, and GE 76, RG 16 and RG 25 a less pronounced negative
      chronotropy. In contrast to the reference compound propafenone, the derivatives
      GE 70, GE 76 and RG 16 lacked any beta-adrenoceptor-blocking activity, while GE
      68 and RG 25 exerted only a weak and nonsignificant effect. It is concluded that
      the formation of a benzofurane ring in the propafenone molecule did not cause a
      prominent change in negative inotropic and negative chronotropic effects, but
      resulted in a decrease or loss of beta-adrenoceptor-blocking activity.
      Additionally, an exchange of the phenylethyl group (GE 68, GE 70, GE 76) on the
      benzofurane ring by a methyl (RG 25) or ethyl group (RG 16), attenuated the
      negative inotropic and chronotropic potency.

PMID- 8861711
TI  - Species difference in the 5-hydroxytryptamine3 receptor associated with the von
      Bezold-Jarisch reflex.
AB  - Species differences in the 5-hydroxytryptamine (5-HT)3 receptor among
      anesthetized rats, mice, rabbits, ferrets, dogs and guinea-pigs were examined in
      the transient bradycardia induced by i.v. injection of 5-HT (the von Bezold
      Jarisch reflex). We also investigated the mechanism of the 5-HT-induced
      bradycardia in these species. 5-Hydroxytryptamine and the selective 5-HT3
      receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide, dosedependently
      decreased heart rate in all species. In anesthetized rats, mice, ferrets and
      guinea-pigs, 2-methyl-5-HT and m-chlorophenylbiguanide behaved as full agonists
      against the 5-HT3 receptor, whereas their agonistic action in rabbits was
      partial. On the basis of ED50 values, there was no marked species difference in
      the potency of 5-HT3 receptor agonists. In contrast, the blocking activities of
      the 5-HT3 receptor antagonists, YM060, YM114 (KAE-393), granisetron and
      ondansetron, were markedly weaker in anesthetized guinea-pigs than in the other
      species. With regard to the mechanism of the 5-HT-induced bradycardia, YM060,
      atropine or vagotomy completely inhibited the 5-HT-induced bradycardia in
      anesthetized rats and mice. In guinea-pigs, in contrast, higher doses of YM060
      and atropine or vagotomy inhibited this reflex by approximately 80%. Although the
      YM060-resistant part of the 5-HT-induced bradycardia in guinea-pigs was affected
      by neither 5-HT2 receptor antagonists nor 5-HT4 receptor antagonists, it was
      completely abolished by methysergide, a 5-HT1-like and 5-HT2 receptor antagonist.
      These results suggest that there is a species difference in the 5-HT3 receptor
      between guinea-pigs and other species in the von Bezold-Jarisch reflex system.
      They also suggest that the 5-HT-induced bradycardia in anesthetized rats and mice
      is evoked by acetylcholine released through activation of 5-HT3 receptors on the
      vagus nerve, while that in guinea-pigs is, at least in part, mediated through 5
      HT1-like receptors in addition to 5-HT3 receptors.

PMID- 8861712
TI  - Age-related alteration of alpha(1)-adrenoceptor mechanisms and Ca2+ inhibitory
      effects of isradipine.
AB  - The effects of age on alpha1-adrenoceptor and Ca2+ channel-mediated contractile
      mechanisms in the thoracic aorta, isolated from rats of 3, 6, 10, 18 and 40 weeks
      old, were studied. The potency (pD(2) value) of norepinephrine increased with age
      from 3 to 10 weeks, but decreased thereafter from 10 to 40 weeks. The change in
      pD(2) value of norepinephrine was proportional to the logarithm of the maximum
      number of binding sites (B(max)), obtained in the [(3)H]prazosin binding study.
      The inhibitory effect of a potent Ca(2)+ channel blocker, israpidine, on the
      norepinephrine-induced contraction decreased with age from 3 to 10 weeks, but
      increased in rats aged 10 to 40 weeks. An inverse relationship between the change
      in isradipine inhibition, the maximum reduction of isradipine on norepinephrine
      induced contraction and the logarithm of B(max) was found. The inhibitory effect
      of a nonselective Ca2+ channel blocker, SKF96365, on the norepinephrine-induced
      contraction did not change with age. The amplitude of the Ca2+-induced sustained
      contraction, after pretreatment with isradipine (10(-7) M) in the presence of
      norepinephrine (10(-6) M), increased with age from 3 to 10 weeks, but decreased
      thereafter in rats aged 10 to 40 weeks. There was no significant difference in
      the slope of the regression lines between the cytosolic Ca(2)+ level ([Ca2+]i)
      and the tension in the presence of norepinephrine at different ages. These
      results suggest that the changes in alpha(1)-adrenoceptor mechanisms and the
      reduction by isradipine with age are due to changes in the alpha1-adrenoceptor
      density and the population of Ca2+ channels, but not to changes in the affinity
      of drugs to the alpha1-adrenoceptor or Ca2+ sensitivity of contractile elements
      of aortic smooth muscles.

PMID- 8861713
TI  - Induction of nitric oxide synthase by endotoxin in rat isolated aorta but not in
      rat aortic smooth muscle cells grown in culture from explant.
AB  - Incubation of endothelium-denuded rings of rat aorta at 37 degrees C for 18 hours
      in Krebs solution led to a profound depression of the contractile actions of
      phenylephrine (1 nM-10 mu M). A major component of this depression of
      vasoconstriction was due to the relaxant actions of nitric oxide since it was
      reversed following inhibition of the synthesis of nitric oxide with N(G)-nitro-L
      arginine methyl ester or its actions with haemoglobin (30 microM) or methylene
      blue (10 mu M). The depression was also reversed upon treatment with LY83583 (0.1
      1 microM which generates superoxide anions, intracellularly and extracellularly,
      but was unaffected by hypoxanthine (100 microM)/ xanthine oxidase (16 mu/ml)
      which generates superoxide anion only extracellularly. The ability of polymixin B
      (30 microM) to inhibit the development of the depression of vasoconstriction
      suggests that it results from the expression of an inducible form of nitric oxide
      synthase, stimulated by bacterial lipopolysaccharide, contaminating the Krebs
      solution. In contrast to aortic rings, we found that lipopolysaccharide (10
      10,000 ng/ml) alone from S. typhosa was unable to stimulate the expression of the
      inducible form of nitric oxide synthase in rat aortic smooth muscle cells grown
      in culture from explant, as assessed either by measuring the accumulation of
      nitrite into the culture medium during a 24 hour incubation period or by
      measuring the smooth muscle cyclic GMP content. Interferon-gamma (1-100 IU/ml)
      and interleukin-1 alpha (1-10 IU/ml) alone were, however, able to stimulate the
      accumulation of nitrite in a concentration-dependent manner. These inductions of
      nitrite accumulation were abolished following treatment with N(G)-nitro-(L)
      arginine methyl ester (1 mM) and dexamethasone (1 microM). Further investigations
      are required to determine whether the ability of bacterial lipopolysaccharide to
      induce the inducible form of nitric oxide synthase in rat aortic rings, but not
      in rat aortic smooth muscle cells in culture, results from the presence of an
      endotoxin-sensitive, cytokine-secreting cell type in the vessel wall which is
      absent in culture, or from differences in smooth muscle phenotype in situ and in
      culture.

PMID- 8861714
TI  - Involvement of tyrosine kinase and protein kinase C in the induction of nitric
      oxide synthase by lipopolysaccharide and interferon-gamma in J774 macrophages.
AB  - The combination of lipopolysaccharide (LPS; 100 ng/ml) and interferon-gamma (IFN
      gamma; 10 IU/ml) synergistically stimulated induction of nitric oxide synthase
      activity in J774 macrophages, measured by nitrite accumulation during an
      overnight incubation. Neither the phorbol ester, phorbol 12-myristate 13-acetate
      (PMA; 10(-9) - 3 x 10(-6) M) nor the calcium ionophore, A23187 (10(-7) - 10(-4)
      M), alone or in combination, stimulated accumulation of nitrite. They were also
      unable to substitute for IFN-gamma in priming J774 macrophages to stimulation
      with LPS. Phorbol 12-myristate 13-acetate (10(-9) - 3 x 10(-6) M) produced a
      concentration-dependent inhibition of nitrite accumulation when added prior to
      stimulation with LPS and IFN-gamma, but enhanced nitrite accumulation when added
      12 hours following stimulation with LPS and IFN-gamma. Of the protein kinase C
      inhibitors tested, staurosporine (10(-9) - 3 x 10(-6) M) and Ro 31-8220 (3 x 10(
      9) - 10(-5) M) produced a powerful, concentration-dependent inhibition of nitrite
      accumulation when added prior to stimulation with LPS and IFN-gamma, but had only
      slight inhibitory effects when added 12 hours after stimulation with LPS and IFN
      gamma. Chelerythrine chloride ( 10(-8) - 3 x 10(-5) M) produced only a slight
      inhibition of nitrite accumulation when added prior to stimulation with LPS and
      IFN-gamma, but slightly enhanced nitrite accumulation when added 12 hours
      following stimulation with LPS and IFN-gamma. The tyrosine kinase inhibitors,
      genistein (10(-7) - 10(-4) M) and herbimycin A (5.2 x 10(-9) - 1.74 x 10(-6) M),
      produced a powerful concentration-dependent inhibition of nitrite accumulation
      when added prior to stimulation with LPS and IFN-gamma. In contrast, herbimycin A
      had only a slight inhibitory effect when added 12 hours following stimulation
      with LPS and IFN-gamma, and genistein had no effect. When used in combination
      prior to stimulation with LPS and IFN-gamma, herbimycin A (1.7 x 10(-7) M) and
      staurosporine (3 x 10(-8) M) produced additive inhibitory effects on nitrite
      accumulation, but herbimycin A, together with Ro 31-8220 (3 x 10(-6) M) or
      chelerythrine chloride (10(-5) M), produced no further effects. These results
      provide strong evidence for the involvement of tyrosine kinases in the induction
      of nitric oxide synthase by LPS and IFN-gamma in J774 macrophages. They also
      suggest a role for protein kinase C, but elucidation of the precise mechanisms by
      which this pathway interacts with tyrosine kinase to regulate the expression of
      nitric oxide synthase requires further investigation.

PMID- 8861715
TI  - Inhalation of phosphoramidon, a neutral endopeptidase inhibitor, induces cough in
      awake guinea-pigs.
AB  - In the present study, we explored whether or not a neutral endopeptidase
      inhibitor provokes cough in awake guinea-pigs. Inhalation of phosphoramidon at a
      concentration of 10(-6) M did not cause cough, but increasing the concentration
      to 10(-5) M caused cough with a latency of about 10 to 12 min. Inhalation of
      enalapril, an angiotensin-converting enzyme inhibitor, did not cause cough, even
      at high concentrations of 10(-5) M and 10(-4) M. Pretreatment with phosphoramidon
      (10(-5) M) significantly increased the number of coughs caused by substance P and
      capsaicin. Capsaicin-induced coughs were more easily produced in bronchitic
      guinea-pigs than in normal guinea-pigs. However, there was no significant
      difference in the number of phosphoramidon-induced coughs between normal and
      bronchitic guinea-pigs. Phosphoramidon-induced coughs were significantly
      depressed by codeine (20 mg/kg, p.o.) and CP96345 (2 mg/kg, i.v.). The present
      results provide new evidence for the proposed idea that neutral endopeptidase may
      regulate the occurrence of cough.

PMID- 8861716
TI  - Cell type-specific expression of the mouse peripherin gene requires both upstream
      and intragenic sequences in transgenic mouse embryos.
AB  - Peripherin is a neuron-specific type III intermediate filament protein expressed
      in well-defined populations of neurons projecting towards peripheral targets. To
      investigate the molecular mechanisms by which a gene is expressed in a specific
      subset of neurons, we used a transgenic approach in order to define peripherin
      gene sequences that are necessary for cell-type specific expression. Transgenic
      mice carrying different various genomic regions of the mouse peripherin gene
      fused to the Escherichia coli lacZ reporter gene were generated. We used three
      different peripherin/lacZ constructs containing either 5.8 kb upstream sequences,
      or both 5.8 kb upstream and 1.1 kb intragenic sequences, or 1.1 kb intragenic
      sequences associated with an heterologous promoter. Analysis of lacZ gene
      expression in transgenic mouse embryos showed that cell type-specific expression
      of the mouse peripherin gene requires both upstream and intragenic sequences.
      Analysis of transgenic mouse lines expressing the construct containing both
      upstream and intragenic sequences showed that this transgene contains all
      regulatory elements essential for both spatial and temporal expression of the
      mouse peripherin gene during embryogenesis. Furthermore, lacZ+ positive cells
      isolated from these transgenic lines by fluorescence-activated cell sorting
      (FACS) can be stained with a peripherin antibody, demonstrating that the
      transgene containing both upstream and intragenic sequences is expressed in
      peripherin neurons. These mouse peripherin upstream and intragenic sequences can
      now be used to identify cis-acting regulatory elements and transcription factors
      involved in peripherin gene regulation.

PMID- 8861717
TI  - Ontogeny of NMDA R1 subunit protein expression in five regions of rat brain.
AB  - A polyclonal antiserum to a fusion protein corresponding to a region of the NMDA
      R1 (NR1) subunit (amino acids 656-811) was produced and affinity purified. A
      quantitative immunoblotting technique was developed using the fusion protein as a
      standard. By employing this method, ontogenic studies (day 2-42) of the density
      of NR1 protein were carried out in several regions of rat brain. The results
      showed that in all five of the brain regions examined [olfactory bulb (Ob),
      cortex (Cx), hippocampus (Hp), midbrain (Mb) and cerebellum (Cb)], levels of NR1
      protein are low at birth and increase with similar patterns having a sharp rise
      within the first 3 weeks after birth. Levels increased 2.0 to 4.5-fold from
      postnatal day 2 to postnatal day 42. Although the general patterns of
      developmental expression are similar, large differences in the absolute amounts
      of NR1 protein among the five brain regions were observed. The maximal levels
      (pmol of fusion protein equivalent/mg +/- S.E.) of NR1 subunit attained during
      development in the five regions are: Hp 2.0 +/- 0.37 > Cx 1.4 +/- 0.11 > Ob 1.3
      +/- 0.2 > Mb 1.0 +/- 0.10 > Cb 0.57 +/- 0.13. The temporal patterns of expression
      of NR1 protein are similar to results from studies examining the expression of
      NR1 mRNA. Furthermore, the absolute numbers obtained from our studies are close
      to those found using [(3)H]MK-801 binding suggesting that many of the NR1
      subunits expressed in the brain exist in an active form.

PMID- 8861718
TI  - Ontogeny of heme oxygenase activity in the hippocampus, frontal cerebral cortex,
      and cerebellum of the guinea pig.
AB  - Heme oxygenase (HO) catalyzes the oxidation of heme to produce carbon monoxide
      (CO), biliverdin and iron. CO is considered to function as a novel neuronal
      messenger in the brain analogous to nitric oxide. The ontogeny of microsomal HO
      activity in the hippocampus, frontal cerebral cortex, and cerebellum of the
      immature fetal, mature fetal and adult guinea pig was determined using an
      optimized assay which quantitated heme-derived CO formation by a gas
      chromatographic method. There was a distinct developmental profile of HO activity
      that was similar for all three brain regions. In particular, HO activity was
      maximal in the mature fetus compared with the immature fetus and the adult. These
      data demonstrate that HO activity is developmentally regulated and that there is
      similar ontogeny of HO activity in the hippocampus, frontal cerebral cortex, and
      cerebellum of the guinea pig.

PMID- 8861719
TI  - Synaptophysin-like immunoreactivity in the rat olfactory bulb during postnatal
      development and after restricted early olfactory experience.
AB  - Synaptophysin is a synaptic vesicle protein that provides a marker of synaptic
      distribution in the brain. We used synaptophysin immunohistochemistry to detect
      changes in synaptic distribution in the main olfactory bulb during normal early
      postnatal development and following early olfactory restriction. Synaptophysin
      like immunoreactivity appears early in the postnatal development of most bulbar
      laminae. In the first postnatal week, the entire glomerular neuropil is stained
      intensely, but by PND 19, the glomerular perimeter becomes more intensely stained
      than its core. This immunoreactivity is especially dense along that aspect of the
      perimeter facing the olfactory nerve layer. To determine if this developmental
      pattern could be affected by early olfactory experience, unilateral naris closure
      was performed on PND 1. In deprived bulbs at PND 19, the difference in staining
      between the glomerular border and the glomerular core is significantly less than
      in either contralateral glomeruli or glomeruli from unoperated animals. The
      difference between the glomerular border and the glomerular core is greater in
      bulbs contralateral to a closed naris than in bulbs from unoperated animals.
      Staining intensity measured over entire glomeruli is not altered by naris
      closure, nor is staining of other laminae. The changes detected after naris
      closure indicate that the glomerular distribution of synaptophysin may be
      particularly sensitive to early olfactory experience.

PMID- 8861720
TI  - The abnormal distribution of mossy fiber bundles and morphological abnormalities
      in hippocampal formation of dreher(J) (dr(J)/dr(J))mouse.
AB  - The organization of pyramidal cells and mossy fibers in the hippocampal formation
      of homozygous dreher(J) mutant mice was investigated using Timm's and Golgi
      methods. Five clear abnormalities were found: (1) some pyramidal cells were
      located below the infrapyramidal mossy fiber layer, (2) mossy fibers emerged in
      diffuse fashion from between the suprapyramidal and infrapyramidal mossy fiber
      layers, and their fibers invaded within the pyramidal cell layer, where they
      traveled as 3-6 small, usually quite short, bundles, (3) some normally situated
      pyramidal cells had unusual contacts with mossy fibers at two or three places on
      their apical and/or basal dendrites, (4) some normally situated pyramidal cells
      had abnormal dendritic trees typified by the occurrence of fine-caliber dendritic
      branches extending out of the apical dendrite or the apical portion of the soma,
      and (5) a few Timm positive fibers extending from the dentate hilus to the
      dentate molecular layer in both dreher(J) and control mice were observed. These
      abnormalities indicate that in the hippocampal formation a variety of cell
      populations and neuronal circuits can be indirectly modified by the dreher
      mutation.

PMID- 8861721
TI  - Development and activity-dependent expression of neuronal marker proteins in
      organotypic cultures of rat visual cortex.
AB  - We are interested in activity-dependent mechanisms which govern the structural
      and functional maturation of neurons in the visual cortex. We have asked whether
      the expression of neuronal markers microtubule-associated proteins tau, MAP-2,
      synaptophysin (p38), and the growth-associated protein GAP-43 are dependent on
      cortical afferents or spontaneous activity. As a model system we have employed
      organotypic monocultures of rat visual cortex (OTCs, isolated from subcortical
      structures) in comparison with visual cortex in vivo (innervated by thalamic and
      other afferents) at different postnatal ages. We know from previous work that the
      OTCs, like the cortex in vivo, display a high rate of spontaneously generated
      action potentials. Therefore, as a third objective, we have analysed OTCs grown
      as monocultures under chronic blockade of spontaneous action potentials. Protein
      expression was detected by protein blots and/or immunohistochemistry. The
      proteins examined in this study are expressed in OTCs, even when grown under
      activity blockade. However, the pattern of expression differs from the cortex in
      vivo. Tau is expressed much weaker in OTCs than in cortex in vivo. The expression
      of the major band of about 50 kDa increases over time in vivo and in OTCs.
      Smaller isoforms of tau are dramatically downregulated, and larger (adult)
      isoforms do not appear within 35 days in vitro (DIV). Under activity blockade the
      expression of tau reaches a maximum by 21 DIV and decreases dramatically, so that
      the protein is hardly detectable by 47 DIV. MAP-2-immunoreactive proteins are
      localized in somata and dendrites, but also persist in axons. The expression in
      OTCs of p38 and GAP-43 correlates well with the expression observed in vivo.
      Synaptophysin (p38) occurs with a similar time course and amount in OTCs as in
      cortex in vivo. Synaptic boutons appear in all layers, and specialized terminal
      elements have been observed. Activity blockade slightly affects the p38
      expression, although the late postnatal decline in p38 immunoreactivity observed
      on protein blots from cortex in vivo and in normal OTCs appears more accentuated
      in activity-blocked OTCs. The GAP-43 expression is prominent from birth onwards
      in vivo and in OTCs. However, in normal OTCs GAP-43 is not declining as it is in
      vivo, although it is downregulated in activity-blocked OTCs. As a major finding
      we report that neuronal markers which are normally expressed in immature neurons
      and axons during the period of differentiation and structural plasticity are
      continuously expressed in OTCs, suggesting that a monocultured cortex retains the
      ability for growth and structural changes longer than the cortex in vivo.

PMID- 8861722
TI  - NGF, BDNF and NT-3 play unique roles in the in vitro development and patterning
      of innervation of the mammalian inner ear.
AB  - Developing cochleovestibular ganglion (CVG) neurons depend upon interaction with
      the otocyst, their peripheral target tissue, for both trophic support and tropic
      guidance. RT-PCR of E11 through E14 otocyst-CVG RNA extracts have shown that NGF
      as well as BDNF and NT-3 are expressed in the developing inner ear (in situ RT
      PCR on tissue sections of E12 otocysts localized all three neurotrophins to the
      otocyst). To evaluate the functional significance of NGF, BDNF and NT-3
      expression, E10.5 otocyst-CVG explants were treated with antisense
      oligonucleotides and compared to sense treated and control cultures. Confocal
      microscopic analysis revealed that treatment with BDNF antisense resulted in
      extensive neuronal cell death, downregulation of NGF caused an inhibition of
      neuritogenesis and a decrease in the neuronal population of the CVG, whereas
      treatment with NT-3 antisense resulted in a loss of target directed CVG neuritic
      ingrowth in this in vitro model. The effect of NGF or BDNF antisense treatment
      could be prevented by the simultaneous addition of the respective growth factor.
      These findings demonstrate that each of the three neurotrophins have important
      roles during the onset of neuritic ingrowth of the CVG neurons to the otocyst.

PMID- 8861723
TI  - Excitotoxic lesions of the rat striatum: different responses of kynurenine
      pathway enzymes during ontogeny.
AB  - Excitotoxic lesions of the adult rat striatum result in reactive gliosis and an
      associated increase in the activities of the astrocytic enzymes 3
      hydroxyanthranilic acid oxygenase (3HAO) and kynurenine aminotransferase (KAT),
      which are responsible for the biosynthesis of the neurotoxin quinolinic acid and
      the neuroprotectant kynurenic acid, respectively. Unilateral ibotenate injections
      were made in the striatum of 7-, 14-, 21- and 28-day- and 2.5-month-old rats to
      study the reaction of 3HAO and KAT when injury is inflicted during ontogeny. By
      one week, all lesioned striata showed a > 50 percent decrease in the activity of
      the neuronal marker enzyme glutamic acid decarboxylase. At this timepoint, lesion
      induced elevations in 3HA0 activity increased progressively from 130 to 206, 280,
      385 and 456 percent of the contralateral striatum in the five age groups studied.
      In contrast, in the same animals the respective increases in striatal KAT
      activity were 601, 350, 312, 259 and 159 percent (n = 6-13 per group). In all age
      groups, statistically significant lesion-induced increases in 3HA0 and KAT were
      seen up to 4 weeks after the ibotenate injection. Rats receiving an intrastriatal
      injection of ibotenate on postnatal day 7 also showed an increase in the striatal
      tissue level of kynurenic acid 1 week after the lesion. These data demonstrate
      that substantial qualitative differences exist between the immature and adult rat
      in the reaction of two glial enzymes to striatal injury. Moreover, the ability of
      the immature brain to mobilize kynurenic acid production preferentially may play
      a role in the brain's response to perinatal injury.

PMID- 8861724
TI  - Distribution of muscarinic receptor subtypes in rat brain from postnatal to old
      age.
AB  - In an effort to understand the developmental changes in the distribution of
      muscarinic receptor subtypes (m1-m5), specific brain regions from juvenile (16
      day-old), young (21-day-old) and adult (90-day-old) rats were analyzed using
      subtype-selective antibodies. These studies revealed significant age-dependent
      changes in the four brain regions examined. In cortex, an area associated with
      higher cognitive functions, significant increases of m2 and m4 receptors occurred
      between juvenile and adult rats. In the striatum, the level of m4 receptor
      increased with age whereas the m1, m2 and m3 receptors had reached mature levels
      within the first 16 days. Small but significant changes occurred in the
      cerebellum with a decrease in m1, m3 and m4 receptor subtypes. In contrast to
      other brain regions, the hippocampus displayed consistent expression levels of
      muscarinic receptor subtypes. Suggesting that this brain region, which is
      involved in the foundation of numerous neural networks, requires a full
      complement of muscarinic receptors at a very early age. Muscarinic receptors have
      been shown to be important in a number of behavioral activities, including
      learning and memory. The changes observed in the age-dependent expression of
      these receptors most likely play an important role in how acetylcholine produces
      its effects in vivo.

PMID- 8861725
TI  - The influence of blood gas changes on hyperthermia-induced seizures in developing
      rats.
AB  - Fever induces seizures in infants with febrile convulsions or epilepsy. Hyperpnea
      induced by fever may contribute to the induction of these seizures. In order to
      examine this possibility, we evaluated the effect of changes in arterial blood
      gas tension on hyperthermia-induced seizures in developing rats. Electrical
      seizure discharges were induced by application of infra-red rays on the skull of
      rats under mechanical ventilation with different respiratory conditions. There
      was positive correlation between pCO(2) and the seizure threshold (ST) defined as
      a latency from the start of hyperthermia to the occurrence of seizures: ST
      (seconds, s) = 2.36 pCO(2) + 0.05 (R(2) = 0.80, P < 0.001). Seizure duration (SD)
      was longer at lower pCO(2) level: 18 (6-33) (median, range) s at pCO(2) ranging
      from 23 to 26 mmHg vs. 0 (0-7) s at pCO(2) ranging from 35 to 57 mmHg (P < 0.01).
      Hypoxia significantly increased ST: 84 (61-100) s at P0(2) ranging from 53 to 76
      mmHg vs. 60 (51-72) s at P0(2) ranging from 87 to 131 mmHg (P < 0.01). Hyperoxia
      prolonged SD: 27 (10-30) s at P02 ranging from 100 to 170 mmHg vs. 9 (0-23) at
      P0(2) ranging from 53 to 93 mmHg (P < 0.02). Hypocarbia caused by fever-induced
      hyperpnea probably contributes to the generation of fever-induced seizures.

PMID- 8861726
TI  - Evidence that large myelinated primary afferent fibers make synaptic contacts in
      lamina II of neonatal rats.
AB  - Choleragenoid horseradish peroxidase (B-HRP) is a retrogradely transported marker
      that selectively labels large cutaneous myelinated primary afferent fibers. In
      adults, B-HRP labelled large afferent fibers are seen to enter laminae III-V, and
      to a lesser extent lamina I, whereas lamina II, which is the major termination
      site of unmyelinated primary afferents, remains unlabelled. In the neonate,
      however, there is extensive B-HRP label in lamina II. The present study shows
      that the B-HRP labelled fibers in the neonate make many synaptic contacts in
      lamina II. This supports the idea that large primary afferent fibers in neonatal
      animals make synaptic contact with post-synaptic targets that presumably process
      nociceptive information. Accordingly to ameliorate pain in neonates it may be
      more important to block low threshold sensory input whereas in adults it would be
      more important to block the high threshold inputs.

PMID- 8861727
TI  - Genomic imprinting and the differential roles of parental genomes in brain
      development.
AB  - Certain genes are expressed either from the maternal or the paternal genome as a
      result of genomic imprinting, a process that confers functional differences on
      parental genomes during mammalian development. In this study we focus on the
      cumulative effects of imprinted genes on brain development by examining the fate
      of androgenetic (Ag: duplicated paternal genome) and parthenogenetic/gynogenetic
      (Pg/Gg: duplicated maternal genome) cells in chimeric embryos. Striking cell
      autonomous differences in the phenotypic properties of the uniparental cells were
      observed. Ag cells contributed substantially to the hypothalamic structures and
      not the cortex. By contrast, Pg/Gg cells contributed substantially to the cortex,
      striatum and hippocampus but not to the hypothalamic structures. Furthermore
      growth of the brain was enhanced by Pg/Gg and retarded by Ag cells. We propose
      that genomic imprinting may be responsible for a change in strategy controlling
      brain development in mammals. In particular, genomic imprinting may have
      facilitated a rapid non-linear expansion of the brain, especially the cortex,
      during development over evolutionary time.

PMID- 8861728
TI  - Spatial organization of calcium dynamics in growth cones of sensory neurones.
AB  - The concentration of calcium ions in the cytosol ([Ca2+]i) has a dominant
      influence on neuronal development. A [Ca2+]i rise can, depending on the amplitude
      and location, promote outgrowth or dramatically inhibit it. We have used the
      fluorescent calcium indicators Fura-2 and Fura-2 dextran to measure [Ca2+]i
      dynamics in sensory neurones from the adult rat. [Ca2+]i was low and uniform in
      advancing growth cones, even during specific behaviours such as protrusion,
      filling and consolidation. A brief train of action potentials caused [Ca2+]i to
      rise at the extreme leading edge of the growth cone. [Ca2+]i changes in more
      proximal regions of the growth cone were much smaller. This spatially organized
      [Ca2+]i change, which may result from a concentration of calcium channels at the
      growth cone leading edge, is likely to function in spontaneously active
      regenerating axons in vivo to specifically activate calcium-dependent processes
      at the growth cone tip.

PMID- 8861729
TI  - Increased levels of kynurenic acid in brains of genetically dystonic hamsters.
AB  - Recent pharmacological studies have shown antidystonic effects of NMDA and non
      NMDA receptor antagonists in an inbred line of Syrian hamsters (dt(sz)) with
      primary generalized dystonia, i.e. a neurological syndrome of sustained muscle
      contractions which occurs in the absence of any pathomorphological alterations.
      This prompted us to examine the levels of kynurenic acid (KYNA), the endogenous
      broad spectrum antagonist of the excitatory amino acid receptors. The
      concentrations of KYNA were determined by HPLC in forebrain, cerebellum,
      brainstem and plasma in dystonic hamsters and age-matched non-dystonic controls.
      Dystonia in mutant hamsters is transient and disappears completely at the age of
      70 days. In order to examine if neurochemical changes are associated with
      dystonia, KYNA was determined at the age of maximum severity (30 days) and after
      remission (70 days). The levels of KYNA were significantly increased in
      forebrain, cerebellum and brainstem (37-130 percent) in dystonic hamsters at the
      age of maximum severity of dystonia (30 days of life) compared to both a
      genetically related non-dystonic inbred line and a non-related outbred line of
      hamsters. The increase of KYNA in brain regions was accompanied by enhanced
      plasma levels. However, there was no correlation between brain and plasma levels.
      Since the changes in KYNA levels disappeared in parallel with dystonia (70 days),
      the present data provide further evidence that abnormal activity of excitatory
      amino acids may be pathogenetically involved in dystonia in mutant hamsters. With
      regard to the recent finding of antidystonic effects of glutamate receptor
      antagonists the increased levels of kynurenic acid may be interpreted as a
      counteracting process to an overactivity of the glutamatergic system.

PMID- 8861730
TI  - Prenatal cocaine exposure leads to enhanced long-term potentiation in region CA1
      of hippocampus.
AB  - Cocaine use by pregnant women is currently of concern for its social and economic
      impact. Clinical studies of cocaine exposed offspring are limited by
      methodological constraints. In this study we used a rabbit model to examine the
      effects of gestational cocaine exposure on substrates of learning and memory.
      Rabbits, 30 to 40 days old, were examined for alterations in synaptic plasticity
      using an intact hippocampal slice preparation. Extracellular recordings revealed
      in utero cocaine exposure predisposed slices to larger long-term potentiation
      compared to controls.

PMID- 8861731
TI  - 1,25-Dihydroxyvitamin D(3) receptors in developing dorsal root ganglia of fetal
      rats.
AB  - We observed immunostaining for the 1,25-dihydroxyvitamin D(3) receptor (VDR) and
      calbindin-D(28k) in neurons, but not glial cells, of fetal rat dorsal root
      ganglia (DRG) from days 13 through 21 of gestation. Dispersed cultures of DRG
      collected from rat fetuses at gestational day 15 also contained epitopes for VDR
      and calbindin-D(28k) in neurons, but not in glial cells. 1,25-Dihydroxyvitamin
      D(3), through VDR, may perform significant functions in the development of
      neuronal cells.

PMID- 8861732
TI  - Systematic screening for pharmacokinetic interactions during drug development.
AB  - The possible involvement of a new chemical entity in pharmacokinetic drug
      interactions is an important safety issue. Not all relevant drug combinations for
      evaluation of the interactive potential of a new drug can be examined. Therefore,
      experiments should be selected to provide information which is valid not only for
      the interaction investigated, but which can be extrapolated to other
      comedications. In this respect the typical approaches currently used, including
      interaction studies with high risk drugs and compounds frequently given as
      comedication, or studies involving standard inhibitors and standard substrates
      are unsatisfactory. A better approach is to characterize drugs according to their
      effects on the underlying pharmacokinetic processes. Indeed, recent progress in
      understanding drug interaction mechanisms and in the development and refinement
      of in vitro test systems enables in many cases experiments to be designed which
      predict the occurrence of drug interactions. This paper illustrates systematic
      investigational procedures based on mechanism of interaction. Interaction
      mechanisms involving drug absorption, distribution, metabolism, and/or excretion
      are briefly summarized. Detailed proposals are derived which allow identification
      of the possible role of a new drug in interaction mechanisms for which valid test
      systems are available. Emphasis is placed on the rational selection of
      experiments with optimal cost-effectiveness. In vitro methods are integrated in
      the schemes wherever possible. In addition, it is proposed that
      pharmacoepidemiological screening, starting in phase II of drug development, be
      used to identify those relevant drug interactions missed by the mechanism-based
      approach. As exemplified by several recently discovered interactions it should be
      possible, by implementation of the proposed procedure, to avoid most serious
      unexpected adverse effects due to pharmacokinetic drug interactions.

PMID- 8861733
TI  - Lack of pharmacokinetic interaction between pantoprazole and diclofenac.
AB  - The new H+/K+ ATPase inhibitor pantoprazole is extensively metabolized by the
      liver. As substituted benzimidazoles may potentially interact with the cytochrome
      P450 system, the influence of pantoprazole on the pharmacokinetics of the NSAID
      diclofenac was investigated. Diclofenac is widely used in the treatment of
      rheumatic diseases and is mainly metabolized in the liver by CYP2C9. Twenty-four
      healthy volunteers (13 male/11 female) completed a randomized crossover study. As
      test they received orally 40 mg pantoprazole and concomitantly 100 mg diclofenac.
      As respective references 100 mg diclofenac or 40 mg pantoprazole were given
      alone. Diclofenac and pantoprazole serum concentrations were measured. Lack of
      pharmacokinetic interaction was handled as an equivalence problem. The 90%
      confidence intervals (CI) of the ratios of the primary characteristic AUC and the
      secondary characteristic C(max) of diclofenac were entirely within the
      equivalence range of 0.8 - 1.25. Hence, no influence of pantoprazole on the
      pharmacokinetics of diclofenac was concluded, either by competition with the
      CYP2C9 or by the reduction of gastric acid secretion. Vice versa, diclofenac did
      not affect the pharmacokinetics of pantoprazole. All treatments were safe and
      well tolerated. No dose adjustment is required during concomitant treatment with
      diclofenac and pantoprazole.

PMID- 8861734
TI  - Difference of the plasma concentration and urinary excretion of allopurinol,
      oxypurinol, and purine bases between dietary intake and fasting.
AB  - To investigate how much the metabolism of allopurinol, oxypurinol, and purine
      bases during dietary intake (total calorie 2,083 kcal, total protein 107.5 g,
      total lipid 74.1 g, total carbohydrate 228.3 g, total purine 180.5 mg) differs
      from that during fast, allopurinol (300 mg) was administered to 5 normal subjects
      after a 6-hour fast and then breakfast was taken. Four and 10 hours after the
      administration of allopurinol lunch and dinner were taken, respectively. Two
      weeks later the same protocol was performed, except for the intake of only water
      instead of diet. The fractional clearances and urinary excretions of oxypurinol,
      uric acid, and the clearance of creatinine were increased by dietary intake,
      compared with the respective ones resulting from fasting. At the same time the
      plasma concentrations of hypoxanthine, xanthine, and oxypurinol were decreased in
      dietary intake, compared with the respective ones in fasting, while the urinary
      excretion of neither allopurinol, hypoxanthine, nor xanthine was affected. These
      results suggest that the administration of allopurinol at bed time (during the
      nocturnal fast) may be more effective than that after breakfast in order to
      decrease the plasma concentration of uric acid.

PMID- 8861735
TI  - No interethnic differences in stereoselective disposition of oral nimodipine
      between Caucasian and Japanese subjects.
AB  - Using stereospecific assays plasma samples of 4 clinical-pharmacological studies
      have been analyzed to obtain enantioselective data on the pharmacokinetics of the
      calcium channel blocker nimodipine in healthy young and elderly Caucasians as
      well as in healthy young Japanese subjects. Basic pharmacokinetics (AUC, C(max),
      t(max), t1/2) and dose-proportionality based on racemic nimodipine plasma
      concentrations after oral single doses of 30, 60, and 90 mg were comparable in
      Caucasian and Japanese subjects. Stereoselective disposition of nimodipine could
      be observed in all cases investigated, resulting in pronounced differences in AUC
      and C(max) values favoring the (R)-(+)-isomer in respect of higher oral
      bioavailability: After single doses of 60 mg nimodipine, for instance, (R)/(S)
      ratios for AUC were ranging from 5.5 - 10.0 (g.mean/SD: 7.4/1.3) in young
      Caucasians, for C(max) from 4.4 - 7.7 (g.mean/SD: 5.9/1.3). Corresponding ranges
      of 4.7 - 5.5 (g.mean/SD: 5.0/1.1) and 4.5 - 6.5 (g.mean/SD: 5.0/1.2),
      respectively, were calculated for Japanese subjects. The mean (R)/(S)-ratios for
      AUC and C(max) of all 4 studies were quite comparable between the 2 ethnic
      groups. The available data suggest that there are neither any differences in
      racemic nimodipine pharmacokinetics in Caucasians and Japanese subjects nor
      interethnic differences in its stereoselective disposition after oral therapeutic
      doses.

PMID- 8861736
TI  - Tyramine pharmacodynamics during combined administration of lazabemide and
      moclobemide.
AB  - The objective of this study was to assess the tyramine pressor sensitivity during
      combined administration of selective and reversible inhibitors of monoamine
      oxidase A and B, viz. moclobemide (300 mg b.i.d.) and lazabemide (100 mg b.i.d.),
      respectively. In part A, 5 healthy male subjects underwent i.v. tyramine pressor
      tests before (baseline) and during (day 7) combined treatment with both drugs.
      The tyramine dose was titrated until an increase in systolic blood pressure of 30
      mmHg was attained. Subsequently, lazabemide treatment was discontinued and i.v.
      tyramine pressor tests were again conducted after 2 - 3 days of moclobemide
      monotreatment. The tyramine pressor sensitivity factor (mean + or - SD) during
      combined moclobemide and lazabemide treatment was 4.2 + or - 0.9 and during
      moclobemide monotreatment 3.1 + or - 1.1. In part B, a separate panel of 8
      subjects received combined treatment with moclobemide and lazabemide for up to 10
      days. Ascending oral doses of tyramine were administered on days 7 - 10 to
      determine the threshold dose eliciting a 30 mmHg increase in systolic blood
      pressure. In comparison to baseline the effects of oral tyramine were potentiated
      by a factor of 13.5 + or - 6.9. The low amount of oral tyramine needed (51 + or -
      20 mg) to induce relevant increases in blood pressure indicates that dietary
      precautions are needed when both MAO-A and B are inhibited by 2 reversible
      inhibitors.

PMID- 8861737
TI  - The effect of co-administration of zolpidem with fluoxetine: pharmacokinetics and
      pharmacodynamics.
AB  - Since early treatment of depression with Selective Serotonin Reuptake Inhibitor
      (SSRI) can be associated with insomnia, daytime antidepressive therapy with SSRI
      is often combined with nighttime administration of a hypnotic. This study
      attempted to evaluate the pharmacokinetic and pharmacodynamic interactions
      between zolpidem 10 mg, a short-acting hypnotic, and fluoxetine 20 mg, an SSRI.
      Twenty-seven healthy male volunteers (mean age 23.5 years, range 20 - 29)
      received zolpidem and fluoxetine in the following open design: zolpidem on night
      1, a morning dose of fluoxetine daily from day 2 through day 18 and zolpidem on
      night 18. Using HPLC, plasma levels of zolpidem, fluoxetine, and norfluoxetine
      were determined throughout night 1 for zolpidem, night 18 for zolpidem,
      fluoxetine, and norfluoxetine on days 16 and 17 for fluoxetine and norfluoxetine.
      Morning psychomotor tests were performed on days 1, 2, 18, and 19. Statistical
      analysis of data consisted of repeated measures of ANOVA. There was no
      significant difference in AUC, C(max), and T1/2 of zolpidem plasma concentrations
      between night 1 (zolpidem) and night 18 (zolpidem and fluoxetine). There was a
      significantly higher zolpidem plasma level at 0.5 hours after dosing together
      with a significantly shorter T(max) on night 18 compared to night 1. There was no
      significant difference in C(min) of plasma fluoxetine and norfluoxetine levels
      between day 16 and 17 of fluoxetine dosing, and there was no difference in T(max)
      between day 17 (fluoxetine) and day 18 (fluoxetine and zolpidem). There was a 3 -
      4% increase in AUC and C(max) of fluoxetine and norfluoxetine plasma
      concentrations in the presence of zolpidem. There was no difference in the next
      morning performance tests after nighttime treatment of zolpidem alone after 17
      consecutive days of fluoxetine treatment, or after zolpidem in the presence of
      steady-state plasma concentrations of fluoxetine. Both zolpidem and fluoxetine
      were well tolerated alone or in combination. It is concluded that the onset of
      action of zolpidem may possibly be shortened in the presence of fluoxetine, but
      no other significant pharmacokinetic or pharmacodynamic interactions occurred
      between zolpidem and fluoxetine.

PMID- 8861738
TI  - A continuous endeavour for high quality standards in applied human pharmacology.

PMID- 8861739
TI  - Epidermal cytokine and neuronal peptide modulation of contact hypersensitivity
      reactions.
AB  - Cellular and molecular mechanisms underlying contact hypersensitivity reactions
      have been, and still are, fields under intense investigation, not only for the
      importance of these reactions in clinical medicine, but also because they are
      considered prototypic of a vast group of T cell-mediated immune diseases of the
      skin. Interestingly, potent contributions by non-bone marrow-derived cells have
      been shown clearly, demonstrating that epidermal cells are far more than mere
      spectators of these reactions, and undergo a functional activation after contact
      with the hapten causing the hypersensitivity reaction. In particular,
      keratinocyte contribution to the onset as well as modulation of contact
      hypersensitivity reactions through the release of a plethora of cytokines, has
      been widely documented. Moreover, an important control over these reactions is
      exerted by local release of neuropeptides by nerve endings. This review paper
      focuses on epidermal cytokine and neuronal peptide modulation of contact
      hypersensitivity reactions, trying to document the complexity of the regulatory
      systems, active during these immune processes of the skin.

PMID- 8861740
TI  - Interleukin 6 in diseases: cause or cure?

PMID- 8861741
TI  - A secreted peptidase involved in T cell beta-endorphin metabolism.
AB  - Beta-endorphin metabolism by CD4+ and CD8+ T cells, and the thymoma cell line,
      EL4, was investigated. In all three cell types, extracellular beta-endorphin was
      metabolized exclusively by a secreted, metal-dependent, thiol peptidase. The
      enzyme activity is expressed constitutively in EL4 cells and following activation
      of CD4+ and CD8+ T cells with anti-CD3 antibody. The enzyme is not one of the
      proteinases associated with cytolytic T cells and does not appear to be identical
      with any previously described beta-endorphin metabolizing enzyme. The enzyme
      cleaves beta-endorphin at approximately equal rates at either of two sites to
      yield beta-endorphin(1-17) (which is gamma-endorphin), beta-endorphin(1-18), beta
      endorphin(18-31) and beta-endorphin(19-31). Evidence in the literature indicates
      that these N- and C-terminal peptides which contain, respectively, the opioid and
      non-opioid receptor binding domains of beta-endorphin, are biologically active.
      Thus, it is likely that this new T cell peptidase has important immunoregulatory
      activity.

PMID- 8861742
TI  - Inflammatory and immunological parameters of disease activity in rheumatoid
      arthritis patients treated with minocycline.
AB  - The objective of this study was to analyze the anti-inflammatory effect of
      minocycline in rheumatoid arthritis. Serum samples of 65 RA patients who
      completed a 26-week randomized double-blind trial of minocycline (100 mg twice a
      day) versus placebo were studied. In this trial some clinical parameters and in
      particular the acute phase response decreased significantly in the minocycline
      treated group. Serum levels of albumin and interleukin-6 (IL-6) were compared
      with CRP levels in order to study the acute phase response. Furthermore,
      rheumatoid factor (RF) and total immunoglobulin isotypes as well as serum levels
      of soluble interleukin-2 receptor (sIL2-2R) were determined in order to study
      immunological parameters of the disease. Immunoglobulins and cytokines were
      measured by ELISA. Serum levels of albumin remained stable, whereas serum CRP
      levels decreased both in the minocycline- and in the placebo-treated group. Serum
      levels of IL-6 decreased in the minocycline-treated group only and this decrease
      was positively correlated with the decrease in CRP levels. Minocycline
      significantly decreased serum IgM-RF, IgA-RF, total IgM and total IgA levels. In
      addition the ratio of IgM-RF/total IgM decreased in the minocycline-treated
      group. No such changes were observed in the placebo-treated group. The anti
      inflammatory effect of minocycline in RA patients may be due to the reduction in
      the synthesis of IL-6 and rheumatoid factor.

PMID- 8861743
TI  - Local popliteal lymph node reactions to hexachlorobenzene and pentachlorobenzene:
      comparison with systemic effects.
AB  - The effects of the presumed autoimmunogenic chemical hexachlorobenzene (HCB), and
      the closely related non-autoimmunogenic pentachlorobenzene (PCB) in the local
      popliteal lymph node assay (PLNA) were investigated. To that end 1-5 mg of HCB,
      equimolar amounts of PCB or the vehicle only, were injected into the hind
      footpads of rats or mice, and the reaction in the draining lymph node was
      evaluated on days 7 and 21 after injection. PLN were isolated, weighed, and cell
      suspensions were prepared to determine PLN cell numbers, and antibody production
      of PLN cells with an ELISPOT assay or a line immunoassay. The extent of the
      lymphoproliferative effect was examined by detection of proliferating cells with
      the BrdU method, and by measurement of paracortex and follicle areas, by combined
      immunohistochemistry and morphometry of PLN cryosections. We demonstrate here
      that HCB elevated PLN weights and cell numbers of the rat PLN, by day 7 after
      injection, but no elevation of antibody production in the PLN. Moreover, HCB
      caused an enlargement of both the PLN paracortical and follicular areas, and an
      elevation of proliferating paracortical T cells. None of the HCB-induced effects
      were found on day 21. HCB caused the same effects in the mouse PLNA, but they
      tended to sustain at least until day 21. Hardly any of the HCB-induced changes
      were found when PCB was injected. Previously, we have shown that oral exposure of
      Wistar rats to HCB elevated the number of splenic T cells and B cells, but also
      the serum levels of (auto-)antibodies and the production of these antibodies in
      the spleen, which is thus only partly in accordance with the results of the local
      reaction to HCB described in this study. This seeming contradiction is discussed.

PMID- 8861744
TI  - Effect of pentoxifylline in rat and swine models of hepatic fibrosis: role of
      fibroproliferation in its mechanism.
AB  - Fibroproliferation was studied in two animal models of liver disease. Oral
      feeding of yellow phosphorus to pigs reproducibly results in fibrosis after 8
      weeks of feeding, extensive fibrosis after 12 weeks and cirrhosis after 16 weeks
      of yellow phosphorus. Bile duct ligation was used to induce cirrhosis in the rat.
      Fibroproliferation was assessed as uptake of tritiated thymidine into fibroblasts
      which had been incubated with monocyte-conditioned medium obtained from monocytes
      of pigs treated with yellow phosphorus or bile duct-ligated rats and compared to
      the corresponding controls. Fibrosis was assessed by collagen content of liver
      sections obtained from the two animal models. The collagen content was determined
      by quantitation of Sirius red/Fast green-stained liver sections. In both animal
      models collagen content was significantly elevated at the conclusion of the
      treatment. Collagen content of liver sections of yellow phosphorus-treated
      animals were elevated (40 +/- 2.7, n = 15) compared to mineral oil-treated
      controls (23 +/- 1.2, n = 12) and collagen levels in the bile duct-ligated rat
      model liver sections were elevated (31.2 +/- 1.6, n = 6) compared to sham
      operated controls (21.6 +/- 0.7, n = 6). The results of the fibroproliferation
      assay indicate that monocytes obtained from pigs treated with yellow phosphorus
      produce fibroproliferative factors during the development of fibrosis. This is in
      contrast to the bile duct-ligated rat model where no differences were observed in
      the production of fibroproliferative factors in the bile duct-ligated rats
      compared to sham operated controls suggesting that this may not be a key event in
      this model of fibrosis. Pentoxifylline treatment of the yellow phosphorus induced
      swine model of hepatic fibrosis has been associated with a marked improvement in
      fibrosis. In this study treatment of fibrotic pigs with pentoxifylline was
      associated with an improvement in liver function tests, a reduction of collagen
      content of liver sections, and reduction in fibroproliferation in pigs receiving
      yellow phosphorus treatment. Fibroproliferative factors were produced during the
      development of fibrosis in the swine model of fibrosis and their effect was
      blocked by pentoxifylline administered in vivo. This is in contrast to the bile
      duct-ligated rat model where pentoxifylline treatment was not associated with
      improvement in liver function tests or reduction of collagen content of liver
      sections and did not alter the fibroproliferative activity of monocyte
      conditioned media. Taken together these results suggest that fibroproliferation
      and increased synthesis of collagen are key events in the yellow phosphorus
      induced pig model of hepatic fibrosis and that the action of pentoxifylline in
      this animal model is likely to be related to its effects on fibroproliferation
      with a subsequent effect on collagen production. This is in contrast to the bile
      duct-ligated rat model where pentoxifylline does not prevent hepatic fibrosis.

PMID- 8861745
TI  - Photofrin II induces cytokine secretion by mouse spleen cells and human
      peripheral mononuclear cells.
AB  - The aim of our study was to find out if Photofrin II, a cytotoxic drug used
      routinely in photodynamic therapy (PDT), can induce immune responses in vitro,
      and to compare its effects with those of the protoporphyrin 9, hemin, which also
      has antitumor properties. We tested the effect of these porphyrins on lymphocyte
      proliferation and secretion of interleukin-2, interleukin-3, tumor necrosis
      factor alpha (TNFalpha) and interferon gamma (IFNgamma), by human or murine
      mononuclear cells (MNC) without an activating light. Both the Photofrin II- and
      hemin-treated cells showed a significant increase in cytokine secretion in the
      presence of suboptimal concentrations of mitogen. Moreover, Photofrin II and
      hemin significantly increased production of TNFalpha and IFNgamma even in the
      absence of mitogen. The cellular binding sites of Photofrin II and hemin to MNC
      were localized by electromicroscopy or fluorescence. Combined stimulation of
      cells by mitogens and porphyrins maintained optimal vital ionic balance of
      potassium, sodium and chlorine in the lymphocytes. In the cells thus treated
      there was a significant increase in intracellular calcium, a vital second
      messenger for lymphokine secretion. We demonstrate that the effect of Photofrin
      II on the immune system involves enhanced cytokine secretion which may account
      for the subsequent tumor eradication by PDT.

PMID- 8861746
TI  - The immunomodulatory and antitumor activities of lectins from the mushroom
      Tricholoma mongolicum.
AB  - TML-1 and TML-2 were two lectins isolated from the mushroom Tricholoma
      mongolicum. They did not differ appreciably in their pH stability and cationic
      requirement for hemagglutinating activity. They both stimulated the production of
      nitrite ions and activated the macrophages in mice. The two lectins were able to
      inhibit the growth of implanted sarcoma 180 cells by 68.84% and 92.39%
      respectively. The growth of tumor cells in the mouse peritoneal cavity was also
      inhibited by the two lectins with TML-2 expressing a greater potency.

PMID- 8861747
TI  - Thalidomide selectively modulates the density of cell surface molecules involved
      in the adhesion cascade.
AB  - The mode of action of thalidomide (THD) in clinical cases of vasculitis is still
      not clear. Expression of adhesion molecules on endothelial cell lines was
      therefore assessed in vitro. THD is capable of changing the density of tumor
      necrosis factor alpha (TNFalpha) induced ICAM-1 (CD54), VCAM-1 (CD106) and E
      selectin antigens on HUVEC. Furthermore, modulation of L-selectin (CD62L) by THD
      can be demonstrated on human leukocytes in vitro. The molecules investigated are
      involved in the neutrophil-endothelial cell interaction and participate in the
      adhesion cascade. Blunting of cytokine induced up-regulation of these adhesion
      molecules may account at least in part for anti-vasculitic effects of
      thalidomide.

PMID- 8861748
TI  - Phosphodiesterase inhibitors suppress proliferation of peripheral blood
      mononuclear cells and interleukin-4 and -5 secretion by human T-helper type 2
      cells.
AB  - It has been suggested that interleukin-4 and -5 (IL-4 and IL-5) are instrumental
      in the control of allergic disease. Elevated levels of IL-4 messenger RNA (mRNA)
      have been detected in numerous foci of atopic activity, including bronchoalveolar
      lavage (BAL) fluid from atopic asthmatics and skin of atopic dermatitis patients.
      IL-5 is important in eosinophil activation, which is a common feature of atopic
      disease. IL-5 mRNA has been detected in BAL fluid from both atopic and non-atopic
      asthmatics, indicating that IL-5 may be a common feature of the two disease
      states. Production of IL-4 and IL-5 by T cells appears to be associated with a
      high affinity cyclic AMP (cAMP) phosphodiesterase (PDE). This study was designed
      to compare the effects of PDE inhibitors Ro20-1724 and theophylline on (1) the
      mitogenic response of peripheral blood mononuclear cells from atopic and non
      atopic individuals and (2) secretion of IL-4 and IL-5 by TH(2) cells after
      activation with PMA and anti-CD3. Both Ro20-1724 and theophylline inhibited
      proliferation of PBMC in a dose-dependent manner. There was no significant
      difference between proliferation of PBMC from atopic versus non-atopic donors,
      but Ro20-1724, a specific PDE IV inhibitor, was more potent at a concentration of
      10(-5)M than theophylline in suppressing lymphocyte proliferation. Similarly,
      both PDE inhibitors suppressed secretion of IL-4 and IL-5 from TH(2)-like cell
      lines in a dose-dependent manner. In conclusion, as Ro20-1724 and theophylline
      inhibit proliferation of PBMC and secretion of IL-4 and IL-5 from human TH(2)
      cell lines, the development of a selective cyclic nucleotide PDE IV inhibitor may
      provide a promising new approach for asthma prophylaxis.

PMID- 8861749
TI  - A comparison of cyclosporine A and cyclosporine G in a rabbit heterotopic cardiac
      transplant model: graft outcome and histological findings.
AB  - Cervical heterotopic heart transplants were performed on 20 male New Zealand
      white rabbits comprising 4 treatment groups. Animals in each group were injected
      daily via the marginal ear vein and received one of the following regimes:
      Cyclosporine A, 10 mg/kg/day; Cyclosporine G, 15 mg/kg/day; cremophor-El,
      3ml/day; or normal saline. Measurement of 24 hour trough blood concentrations
      revealed no significant differences between the average concentrations of
      Cyclosporine A and Cyclosporine G. Animals were examined daily and the cervical
      allografts assessed by palpation for viability/rejection. The duration of the
      study ended for each animal when the graft stopped beating at which time the
      animals were euthanized and the transplanted heart and native kidneys harvested
      and processed for light microscopy evaluation of rejection and drug toxicity,
      respectively. Graft survival in the Cyclosporine A group significantly surpassed
      that seen in the Cyclosporine G group as well as the control groups, whereas in
      animals treated with Cyclosporine G, graft survival was not different from
      controls. In the native kidney, there were no differences in glomerular tuft area
      or volume density amongst drug-treated or control animals. In contrast, tubule
      atrophy and interstitial fibrosis were markedly greater in Cyclosporine A-treated
      vs Cyclosporine G-treated animals. The results of this study indicate that,
      whereas Cyclosporine G is less nephrotoxic than Cyclosporine A, given equivalent
      blood concentrations Cyclosporine A delays rejection of a cardiac allograft
      significantly longer than Cyclosporine G in this animal species.

PMID- 8861750
TI  - Ultrastructural studies on myofibrillogenesis and neogenesis of skeletal muscles
      after prolonged traction in rabbits.
AB  - Little is known about the morphological response of muscle after long term
      traction. The purpose of this study was to investigate the morphological changes
      of skeletal muscle during limb lengthening. After application of mini
      extraskeletal fixator, the hindlimb of New Zealand white rabbit was osteotomized
      and then slowly lengthened at the rate of 1 mm/day up to a 20 mm gain in length.
      The muscles of hindlimbs were perfused and dissected. Morphological studies were
      performed at electron microscopic level. Transmission electron microscopy
      revealed foci of microtrauma at the myotendinous junction. The distance between
      the muscle fibers and tendon parenchyma increased, with numerous primitive
      mesenchyme-like cells interposed within this gap. The cytoplasmic space of these
      cells was devoid of myofibril formation at the ends of stretched fibers. Within
      the satellite near the myotendinous junction myofilament production was observed
      in various gradations of maturation. It is concluded that myofibrillogenesis with
      traction neogenesis of skeletal muscle during limb lengthening does exist and
      occurs mainly near the myotendinous junction. The myotendinous junction in mature
      skeletal muscle actively participated in the process of limb lengthening.

PMID- 8861751
TI  - A change in the localization of the region trapping immune complexes in rat
      popliteal lymph nodes during development of germinal centers, with regard to the
      distribution of follicular dendritic cells.
AB  - A study was conducted to clarify changes in the relationship between the region
      of immune complex (IC) trapping by follicular dendritic cells (FDCs) and the
      distribution of FDC during reaction of germinal centers (GCs), and to examine the
      relationship between the tridimensional shape of the IC-trapping regions and
      their two-dimensional shape. Five-week-old rats were given footpad injections of
      sheep red blood cells, and then their popliteal lymph nodes were excised between
      days 0 and 42, 24 h after injection of peroxidase-antiperoxidase complex (PAP) as
      an IC. The specimens were immunostained for PAP trapping on serial paraffin
      sections, and for S-100 protein as a marker of FDCs. It was found that during the
      GC reaction, PAP trapping became weak and then disappeared on the basal side of
      developing GCs where S-100 protein-positive FDCs were still present. All of the
      1933 lymph follicles examined were found to trap PAP. Whereas the tridimensional
      shapes of the trapping regions showed similar patterns according to the
      development of lymph follicles, their two-dimensional shapes varied. We suggest
      that FDCs in primary follicles may differentiate into FDCs in the light zone and
      FDCs in the dark zone in secondary follicles. To evaluate each of the
      compartments of a lymph follicle more accurately, investigators should pay
      attention to the tridimensional shape of the compartment.

PMID- 8861752
TI  - Ultrastructural localization of substance P-like immunoreactivity in the
      intermediolateral column of spontaneously hypertensive rats and Wistar-Kyoto
      rats.
AB  - The distribution of substance P in the intermediolateral column of the upper
      thoracic spinal cord of spontaneously hypertensive (SHR) rats and Wistar-Kyoto
      (WKY) rats was studied by combined retrograde tracing of choleragen subunit-B
      horseradish peroxidase (CB-HRP) and immuno-electronmicroscopy. In the T(1)-T(3)
      segments of the spinal cord, SP-like immunoreactive products were localized in
      the cell bodies and dendrites of the sympathetic preganglionic neurons as well as
      in a few pre-axon terminals or axon terminals. In the neuropil of the
      intermediolateral column (ILN), different synaptic configurations were observed
      including synaptic contacts between SP-like positive dendrites and negative axon
      terminals, and between SP-like positive axon terminals and SP-like positive
      dendrites. Furthermore, a single SP-like positive dendrite was sometimes
      postsynaptic to several axon terminals, a feature typical of glomerular synapses.
      The present findings suggest that most of the SP-like immunoreactive elements in
      the ILN were of intraspinal origin derived mainly from the sympathetic
      preganglionic neurons in SHR and WKY rats. Since there was no ultrastructural
      difference in the distribution of SP between the neural elements in the ILN of
      SHR and WKY rats, the present findings also suggest that SP may not be directly
      involved in the hyperactivity of the sympathetic nervous system in hypertension.

PMID- 8861753
TI  - Heterogeneous ultrastructure of melanosome formation in the goldfish induced by
      osmotic stress.
AB  - In this study, melanophore cytodifferentiation in the fins of xanthic goldfish
      that had been exposed to osmotic stress for 18 days was investigated. It was
      found that multi-vesicular bodies (MVB) are not the only type of premelanosome.
      Granules having a homogeneous matrix also function as premelanosomes. The
      presence of acid phosphatase reaction product inside the melanin granules
      indicated that these organelles in this animal were also related to lysosomes.
      DOPA-oxidase of tyrosinase, the key enzyme in melanogenesis, was surprisingly not
      only detected in melanocytes but also in the Golgi stacks of dermal cells. Due to
      the mechanisms of premelanosome formation it is evident that cytoplasmic material
      also serves as substrate for melanogenesis. EDX microanalysis was performed to
      measure the ionic composition of the melanin granules. After aldehyde fixation
      the newly-formed melanin granules did not contain Na, but had accumulated Ca.

PMID- 8861754
TI  - Tenascin and type IV collagen expression in liver cell dysplasia and in
      hepatocellular carcinoma.
AB  - The extracellular matrix (ECM) located in and around tumors is different from
      normal organ stroma, and there is evidence that it is critically involved in
      carcinogenesis and malignant growth. Whereas an abnormal composition of ECM in
      hepatocellular carcinomas (HCC's) has previously been demonstrated, not much is
      known so far with respect to putative HCC precursor lesions. We have, therefore,
      systematically analyzed the immunohistochemical reactivity for two major ECM
      components, tenascin and type IV collagen, in three types of liver cell dysplasia
      (LCD), and compared the findings with patterns observed in HCC's of different
      types and grades. Tenascin reactivity was generally stronger in HCC's than in
      cirrhosis. In cirrhotic nodules harboring areas of LCD, tenascin expression was
      significantly lower in small cell LCD than in large cell LCD. Type IV collagen
      reactivity in and around HCC's decreased as a function of a lower differentiation
      grade. In both groups of cirrhosis, i.e. with or without HCC, cirrhotic nodules
      occupied by the small cell variant of LCD exhibited a significantly lower type IV
      collagen reactivity than those with large cell LCD or simple regenerative cells.
      Taken together these findings suggest that, similar to adenomatous hyperplasia,
      small cell LCD is characterized by an abnormal tenascin and type IV collagen
      expression, thus reflecting the defective ECM pattern observed in HCC's.

PMID- 8861755
TI  - Expression of cytoskeletal proteins and ATPase activity in bovine femoral artery
      and vein intima.
AB  - Intimal cells play an important role in the biology of the vascular wall.
      Variability in the metabolic activity of intimal smooth muscle cells (SMC), as
      well as the differential expression of cellular cytoskeletal proteins depend on
      factors such as degree of differentiation, aging, atherosclerosis, etc. Myosin
      ATPase activity and cytoskeletal proteins were studied in the intima of bovine
      femoral arteries and veins of mature animals. In some arteries the intima was
      thickened and two distinct layers--inner elastic hyperplastic (EHL) and outer,
      musculo-elastic (MEL) were observed. ATPase activity was well defined in
      endothelial cells (EC) as well as in SMC. However, differential enzymatic
      expression was observed in thickened intimas. SMC in the EHL were ATPase
      negative, while in the MEL they were ATPase positive. All EC and SMC in the
      "normal" intimas were vimentin positive, desmin and cytokeratin negative. In
      vessels with thickened intimas, the EHL showed intensive vimentin positivity; in
      the MEL desmin immunoreactive SMC were numerous as were as those in the media.
      Vimentin-positive SMC occupied their innermost part. Differences in the
      expression of ATPase activity and cytoskeletal proteins is discussed in terms of
      possible migration of medial SMC and/or morphological modulation observed in
      vessels with altered vascular walls.

PMID- 8861756
TI  - A new morphological classification during follow-up in patients with celiac
      disease: a three-dimensional observation by scanning electron microscopy.
AB  - The structure and ultrastructure of the villi of small intestinal mucosa was
      examined in 237 duodenal or jejunal biopsies taken from children with active
      celiac disease and during gluten-free diet. All biopsies were processed for light
      and scanning electron microscopy. Conventional histology showed four different
      morphological aspects: total and subtotal villous atrophy in patients on
      unrestricted diet, partial villous atrophy and normal mucosa during gluten-free
      diet. Scanning electron microscopy demonstrated that in active celiac disease the
      severity of the intestinal lesions was related to individual vulnerability to
      gluten. Our results showed that during dietary treatment the process of mucosal
      healing was constant and strictly time-dependent. Furthermore, the
      ultrastructural examination has been relevant in evaluating the evolution of the
      villous regeneration. In this study a classification regarding the healing
      process of the small intestinal mucosa correlated with the time of start of
      dietary therapy is proposed.

PMID- 8861757
TI  - New insights into the cytodynamics of the hamster Harderian gland as provided by
      the bromodeoxyuridine-labelling method.
AB  - The fourth week of postnatal life is a critical point in the development of the
      hamster Harderian gland. During this week, cells with large lipid vacuoles (type
      II cells) appear in the male gland, marking a morphological sex difference that
      is notorious in adult animals. The origin and fate of type-II cells are
      controversial. To gain insight into the mechanisms by which type-II cells become
      a major cell type in the gland of adult male hamsters, bromodeoxyuridine (BrdU)
      labelling was used to assess the proliferative activity of both types of
      glandular cells in 28-day-old animals. To search for possible sex differences in
      the proliferative activity of this gland, female animals of the same age as the
      males were also studied. No difference was found in the overall labelling index
      (BrdU-labelled cells/100 cells) between males (1.8 +/- 0.1%) and females (1.5 +/-
      0.1%). In the gland of the males, the specific labelling index of type-II cells
      (3.4 +/- 0.4%) was significantly higher than that of type-I cells (0.9 +/- 0.2%).
      Interestingly, the proportion of type-II cells present in the male glands at this
      age (36.6%) was significantly lower than that of type-I cells. Our results
      strongly suggest that the proliferation of type-II cells, rather than a
      continuous differentiation of these cells from preexisting type-I cells, is a
      major event in the achievement of the mature form of this gland. The results
      reported here counsel a reappraisal of current theories about the cytodynamics of
      the hamster Harderian gland.

PMID- 8861758
TI  - Initiation and post-initiation chemopreventive effects of beta-carotene in toad
      liver carcinogenesis.
AB  - Hepatocellular carcinoma were recognized in the toad, Bufo viridis, in 14 cases
      out of 50 by injection of 1 mg 7,12 dimethylbenz(a)anthracene (DMBA)/toad
      twice/week for 12 weeks. In contrast, toads treated with DMB at the same dose
      level and beta-carotene (betaC), 0.05 mg (3 hr prior to the carcinogen)/toad,
      twice/week for 12 weeks showed no tumor incidence. However, betaC at the same
      dose level was less effective when administered 3 hr. after the carcinogen
      (DMBA). In 8 cases out of 50 cases neither tumor growth nor neoplastic changes
      were observed in toads treated with betaC alone or olive oil. It is concluded
      that betaC completely blocked hepatocarcinogenesis in toads when given 3 hr.
      before initiation.

PMID- 8861759
TI  - Morphological changes of autoclaved autogenic bone implantation and autoclaved
      autogenic bone supplemented with allogenic demineralized bone matrix in rat
      parietal bone.
AB  - The healing process of resected, autoclaved (121 degrees C, 20 minutes) and re
      implanted bone in the rat parietal bone was compared with that of autoclaved bone
      that was supplemented with allogenic bone matrix (AAA-bone), using a scanning
      electron microscope and a light microscope. In the implant without AAA-bone, bone
      union and replacement of the autoclaved bone was seen at 2 weeks after
      implantation. There was no evidence of any inflammatory reaction around the
      autoclaved bone. The implant was gradually replaced by the new bone. In the
      implant with AAA-bone, the new bone formation around the implanted bone was more
      abundant than that of the implant without AAA-bone. An inflammatory reaction was
      also observed after 1 week. The replacement of the implant with AAA-bone was
      inferior to the nonsupplemented group. The reason for the poor replacement was
      the disturbance of the blood supply in the implant by abundant new bone
      formation. In these results, the autoclaved bone re-implantation was an excellent
      bone substitute with osteoconductive ability and biocompatibility. The
      implantation with AAA-bone was good for the new bone formation, but the position
      and the technique of supplement with AAA-bone have to be more deeply
      investigated.

PMID- 8861760
TI  - Odontogenic jaw cysts: light and electron microscopical investigations.
AB  - Light and electron microscopy were used to analyze the epithelial lining of
      odontogenic cysts excised from edentulous regions of the jaws. Clinically, three
      cases were identified as keratocysts, and 21 cases as cysts other than
      keratocysts ("non-keratocysts"). The epithelium of the former was found to
      achieve keratinization over most of the surface and to never contain mucus
      secreting cells. The epithelium of the latter appeared to be in part stratified
      squamous, with cells loosely connected to each other, and in part stratified
      columnar, with superficial cells connected to each other by tight junctions and
      secreting mucus. The results suggest that cysts arising from edentulous regions
      of the jaws may be either keratocysts or cysts with heterogeneous, non
      keratinizing epithelium; the content of keratocysts can be formed mainly by
      shedding of cornified epithelial layers, and that of non-keratocysts by mucus
      secretion from columnar epithelium associated to fluid filtration through non
      keratinizing squamous epithelium.

PMID- 8861761
TI  - Pattern of degeneration of the rat inferior olivary complex after the early
      postnatal axotomy of the olivocerebellar projection.
AB  - Neuronal death of inferior olivary neurons after early axotomy of the
      olivocerebellar tract was studied in newborn (P1) hemicerebellectomized rats
      during the first six days after lesion. The degeneration of the inferior olive
      showed a topographic pattern from one (P2) to six days after axotomy (P7), after
      which this complex had almost completely disappeared. The first degenerative
      changes were observed in the principal olive (P2), while the medial accessory
      olive was the later-degenerated area (P5). The analysis of these degenerative
      changes provides a reference for future experimental studies. Furthermore, the
      topographic study of the degenerative process demonstrated that: i) the most
      vulnerable neurons were dorsolaterally located, whereas the most resistant ones
      occupied the medial aspect of the inferior olivary complex, ii) the comparison
      between the topographical arrangement of the inferior olivary neurons according
      to their birth dates, and the rate of degenerative changes observed after
      hemicerebellectomy, open the possibility that the neuronal generation date and
      the response to the axotomy of the inferior olivary neurons could be related.

PMID- 8861762
TI  - Stereology of human fetal adrenal medulla.
AB  - Stereological studies were performed on 27 pairs of adrenal glands of human
      fetuses (9-38 weeks of intra-uterine development). Medullary chromaffin cells
      were identified by immunostaining for chromogranin-A. The volume of adrenal
      medulla, average cell volume, and the number of chromaffin cells were calculated.
      The volume of adrenal medulla increased slowly up to the 20th week and afterwards
      it enlarged rapidly to the 31 st week of the fetal period. A gradual, linear
      increase in the number of chromaffin cells of developing adrenal medulla was
      observed during the studied period. On the contrary, the average volume of the
      adrenal medullary cells remained quite constant until the 17th week of the
      development. Afterwards, a gradual, linear increase in the cell volume was
      observed until the 31 st week, reaching a plateau by the end of intra-uterine
      development.

PMID- 8861763
TI  - Modulation of the glycoconjugate expression in the tracheo-bronchial epithelium
      during sustained hypovitaminosis A.
AB  - The aim of this study was to determine the influence of sustained marginal
      vitamin A deficiency on the morphology of glycoconjugate expression in the
      tracheobronchial epithelium of guinea pigs. The distribution of oligosaccharide
      chains was investigated by applying a panel of 24 lectins. Glycosaminoglycans
      were detected by histochemical techniques. Number as well as morphology of
      ciliated cells showed no significant alterations in hypovitaminosis A. In
      contrast, the quantity of goblet cells was constantly decreased. A considerable
      reduction of secretory granules was also observed in these cells. Cytomembranes
      of ciliated cells (especially in the area of ciliar extensions) showed constant
      alterations in the patterns of lectin binding in vitamin A-depleted guinea pigs.
      Our results demonstrate a significant augmentation of accessibility of fucosyl
      molecules in proximal domains of glycoconjugates of ciliary membranes, whereas
      the presence of mannose structures seemed unchanged. In distal bronchioli,
      terminal N-acetylgalactosamine molecules were expressed. During marginal vitamin
      A deficiency, ciliary cells were specially labelled by GSA I(B), indicating
      presentation of terminal galactose molecules in alpha-position. Additionally, the
      cytoplasm of epithelial cells demonstrated enhanced concentrations of
      polyantennary oligosaccharide core structures. Staining of epithelial cells by
      VVA was restricted to control specimens. Abundance of N-acetylglucosamine
      residues on the non-reducing terminus of oligosaccharides was significantly
      enhanced in the connective tissue of depleted animals as demonstrated by the
      binding patterns of GSA II. We suggest that altered oligosaccharide patterns may
      contribute to enhanced predisposition to tracheobronchial infection in marginal
      vitamin A deficiency.

PMID- 8861764
TI  - Microgravity in the STS-29 space shuttle discovery affected the vestibular system
      of chick embryos.
AB  - Out of 32 embryos flown (16 @ E2 + 16 @ E9) for 5 days, 16 survived. All sixteen
      E2 were dead at landing. Eight were opened and eight were incubated at 1.0G.
      Autopsy showed that 4 E2 survived over 24 hours in space. Eight E14 hatched
      without anatomical malformations, and 8 E14 were fixed. The height of the macular
      epithelia was 31 mu m (mean) in control and 26 mu m in flight chicks. The cross
      sectional area of macular nuclei of control was 17 mu m(2) for hair cells and 14
      mu m(2) in supporting cells. In flight, cross-sectional area was 17 mu m(2) in
      hair cells and 15 mu m(2) in supporting cells (n=250). The shape factor of
      cartilage cells (1.0 = perfect circle) between control (mean = 0.70) and flight
      (mean = 0.72), and the area of cartilaginous cells between controls (mean = 9 mu
      m(2)) and flight (mean = 9 mu m(2)) did not differ (n=300). The nuclei of support
      cells were closer to the basement membrane in flight than in control chicks. The
      immunoreactivity of otoconia with anti keratan, fibronectin or chrondroitin
      sulfate was not different between flight and control ears. There were more
      afferent fibers inside the macular epithelia of flight (p<0.05) than control.
      Three of 8 flight animals had elevated vestibular thresholds (VT), with normal
      mean response amplitudes and latencies. Modified afferent innervation patterns
      requiring weeks to compensate are sufficient to elevate VT, and should be
      investigated further. Other reversible (sublethal) microgravity effects on
      sensory epithelia (vacuoles, swelling, etc) require quantification.

PMID- 8861765
TI  - Seasonality and freezability vs routine parameters in stallion semen.
AB  - The fertilizing ability of stallion semen was analyzed using fresh and frozen
      samples, obtained before (June-July) or during (October-November) the breeding
      season. Thirty ejaculates obtained from 4 stallions were used. The analysis
      comprises routine seminogram; ATP concentration (Comhaire et al., 1983);
      subjective and objective motility and sperm velocity (Makler, 1980). Freezing was
      done following the technique of Martin et al. (1979). Sperm velocity, ATP content
      and objective motility in ejaculates of subjective motility >50% show values of
      14.0 + or - 0.84 mu m s(-1); 4.8 + or - 2.7x10(-7)M and 54.0 + or - 7.4%,
      respectively. For ejaculates with subjective motility <50%, these values are 8.4
      + or - 2.4; 0.74 + or - 0.36x10(-7)M and 27.0 + or - 0.8%. No significant changes
      in these characteristics were elicited by freezing, though ATP content dropped to
      50% after thawing. These characteristics are highly associated between them
      (p<0.05) and with some conventional parameters of the routine seminogram such as
      sperm motility, count, total spermatozoal number and morphology. Additionally,
      sperm chromatin packing was analyzed by decondensing sperm nuclei using a thiol
      reducing agent. This parameter was not modified by freezing and it may depend on
      prolonged epididymal sperm storage during the non-breeding season. Epididymal
      maturation then results in an excessive disulphur bridging in sperm basic
      proteins, so that hypermaturation with faulty male pronuclear formation can
      follow.

PMID- 8861766
TI  - Expression of transforming growth factor beta isoforms and their receptors during
      hair growth phases in mice.
AB  - Transforming growth factor beta (TGF-beta) is a family of potent growth inhibitor
      proteins, often produced as a precursor and often secreted in a complex with the
      latent TGF-beta binding protein (LTBP). We investigated the expression of TGF
      beta 1, -beta 2, -beta 3, LTBP, TGF-beta receptor proteins type I and type II (T
      beta R-I and -II) during induced hair growth in C57 BL-6 mice. We here
      demonstrated that TGF betas and T beta R-I are expressed in hair follicle
      epithelium and have found a positive reactivity for LTBP and T beta R-I in
      ++sebocytes. Dermal tissue was weakly stained for LTBP and TGF-beta 3. In early
      anagen the inner hair root sheath epithelium expressed TGF-beta 1, whereas outer
      hair root was positive for T beta R-I during anagen/catagen switch. T beta R-II
      was found in sebaceous glands without significant variations during the hair
      cycle. We may conclude that in follicle epithelium TGF-beta 1 is not produced in
      a complex together with LTBP. On the other hand, it is possible that other types
      of LTBP, like LTBP-2 and LTBP-3, are present, which are not detected by the
      antibody we used. Furthermore, a very rapid secretion of LTBP from producing
      cells may prevent immunohistochemical detection. TGF-beta 1 released by inner
      hair root sheath may regulate outer root sheath growth. A bidirectional
      interaction of sebocytes and hair follicle epithelium in the TGF-beta/LTBP seems
      possible. Sebocytes can be considered to be a target for TGFs since they express
      both T beta R++-I and -II. The general properties of TGF-beta as a growth
      inhibitor of epithelial cells may suggest a possible involvement in either the
      abrogation of extensive growth at the end of anagen or the initiation of catagen
      for the follicle epithelium as well as growth control for sebaceous glands.

PMID- 8861767
TI  - Retinal pigment epithelial fine structure in the Australian Galah (Eolophus
      roseicapillus) (Aves).
AB  - As part of a comparative morphological study, the fine structure of the retinal
      epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has
      been investigated by light and electron microscopy in the galah (Eolophus
      roseicapillus), an Australian cockatoo. The RPE consists of a single layer of low
      cuboidal cells joined basally by a series of zonulae occludentes. Basally
      (sclerally) the retinal epithelial cells display numerous deep infoldings while
      apically (vitreally) microvillar processes interdigitate with photoreceptor outer
      segments. Internally the RPE cells show a large vesicular nucleus, plentiful
      smooth endoplasmic reticulum (SER) and numerous polysomes but very little rough
      endoplasmic reticulum (RER). Numerous mitochondria are located basally. In the
      light-adapted specimens studied, the melanosomes of the RPE are almost
      exclusively located within the apical processes indicating that retinomotor
      movement of this pigment probably occurs. Phagosomes and lysosome-like bodies are
      present as are myeloid bodies which may show ribosomes on their outer surface.
      The choriocapillaris endothelium is thin but only minimally fenestrated facing
      Bruch's membrane. Most fenestrations of the choriocapillaris display a single
      layered diaphragm while the remainder have a double-layered diaphragm. Bruch's
      membrane (complexus basalis) is typical of avian species in that it is
      pentalaminate with the central lamina densa displaced towards the
      choriocapillaris.

PMID- 8861768
TI  - The intracellular origin of the melanosome in pigment cells: a review of
      ultrastructural data.
AB  - This paper is a review about the ultrastructural data dealing with the origin of
      the melanin granules in retinal pigment epithelial cells, in melanocytes, in the
      ink gland of cuttle fish, in Kupffer cells of the liver, in neuronal tissues, in
      cultured pigment cells. The role and structure of lysosomes in melanogenesis are
      discussed in a separate chapter. The early steps of melanogenesis are
      ultrastructurally very heterogeneous, even in the same cell types. With respect
      to this heterogeneity and the considerably different views on melanosome origin
      in the literature, the author hypothesizes that pigment cells may use protein
      matrices originated from different cellular pathways. 1) They may either produce
      a specific protein matrix and be converted into melanin in the classical way, or
      2) alternatively, a matrix resulting from lysosomal protein degradation or
      endocytotic pathways may be used and converted into melanin, as found in
      fibroblasts transfected with the tyrosinase gen or in Kupffer cells. The very
      heterogeneous ultrastructure of the polymerizing melanin may be influenced by the
      amount and sterical availability of tyrosine residues in the protein moieties and
      the activity of tyrosinase.

PMID- 8861769
TI  - Alterations in the alveolar epithelium after injury leading to pulmonary
      fibrosis.
AB  - This review discusses current knowledge of the involvement of the alveolar
      epithelium in tissue remodelling during fibrogenesis. The purpose of the present
      paper is to give an overview, including the authors' own results, of knowledge of
      ultrastructural alterations, proliferation kinetics and phenotypic changes of
      pneumocytes in experimental and clinical pathology of pulmonary fibrosis. After
      lung injury, the alveolar epithelial cells show ultrastructural alterations,
      hypertrophy and hyperplasia, and a modulation of a series of structural and
      membrane proteins such as cytoskeletal changes, loss or de novo expression of
      epithelial adhesion molecules, and altered lectin binding. Furthermore, enhanced
      secretion of proteases, of cytokines and other soluble factors can be observed in
      the alveolar epithelium. These findings suggest the contribution of the
      epithelium in the remodelling process to be greater than expected. Estimations of
      the cell kinetics show that type II pneumocytes have the proliferative capacity
      to restore high proportions of damaged type I cells within few hours. In fibrosis
      this capacity also seems to be affected seriously, resulting in transitional
      phenotypes between type II and type I cells. Additionally, in the light of the
      detection of CD44 type of adhesion molecules at the foot processes of type II
      pneumocytes, some aspects of epithelial-fibroblast interaction are described.

PMID- 8861770
TI  - Neuropeptide Y-related peptides and hypothalamo-pituitary-adrenal axis function.
AB  - Current data on the localization of neuropeptide Y-related peptides in the
      hypothalamo-pituitary-adrenal gland (HPA) axis as well as the effects of these
      peptides on the function of cells comprising HPA axis are presented and
      discussed. The action of neuropeptide Y, peptide YY, and pancreatic polypeptide
      on HPA axis are evaluated. Moreover, we report the presence of pancreatic
      polypeptide immunoreactivity in subset of chromaffin cells in the medulla of rat
      adrenal gland.

PMID- 8861771
TI  - Nonerythroid membrane skeletal proteins in normal and diseased human skin.
AB  - A number of reports have described the presence and localization of membrane
      skeletal proteins in nonerythroid tissues and cultured cells. Interactions of
      these proteins, which have been extensively characterized in erythrocytes, may be
      physiologically important in other cell types. This review focuses on recent
      developments concerning proteins analogous to erythrocyte spectrin, protein 4.1,
      adducin and ankyrin in epidermal keratinocytes, and discusses their significance
      from physiological and pathological stand points. Keratinocyte proteins are
      involved in a wide variety of functions such as the cell-to-cell and cell-to
      substratum adhesion, stratification, and maintenance of the cell shape. In
      epidermal keratinocytes, these nonerythroid membrane skeletal proteins may play a
      role in maintaining the polarity of membrane proteins by connecting them to the
      cytoskeleton, regulating cell-cell interdigitations and stabilizing newly
      synthesized cell membranes before elaboration of cell-cell interdigitations.
      Furthermore, altered expression and distribution of these proteins may be
      important in the pathogenesis of skin disease such as psoriasis.

PMID- 8861772
TI  - Use of lectin-probes for correlative histochemical and biochemical assessments of
      the glycosylation patterns of secretory proteins, including kallikreins, in
      salivary glands and saliva.
AB  - Labelled lectins were used as probes to study the glycosylation and secretion of
      submandibular glycoproteins not only in sections of fixed glands but also in
      glandular extracts and in nerve-induced saliva, after electrophoretic separations
      and immobilization in nitrocellulose membranes. In cats the glycoproteins in
      sympathetic saliva differed considerably from those in parasympathetic saliva. In
      sympathetic saliva they were found to originate mainly from striated ducts, to
      some extent from demilunar cells and to a small extent from acinar cells, whereas
      in parasympathetic saliva they arose mainly from acinar cells and demilunes and
      only to a small extent from striated ducts. In rat submandibular glands
      sympathetic stimulation caused extensive depletion of lectin stainable granules
      from granular tubules. Corresponding strong binding occurred with the same
      lectins to constituents in saliva that ran between 25 and 35 kD on SDS gel
      electrophoresis and were shown to contain tissue kallikreins. Their binding
      patterns suggested that individual kallikreins from the same gland may be
      glycosylated in different ways. This possibility was tested on five different
      kallikreins after separation from submandibular extracts by isoelectric
      focussing. Lectin bindings on slot blot preparations of these kallikreins were
      tested before and after N-glycosidase F, sialidase or endo-alpha-N
      acetylgalactosaminidase digestions. Results showed that, despite their close
      genetic and structural similarities, the kallikreins are in fact differently
      sialylated and fucosylated and the novel finding that some contain O
      glycosidically linked side chains as well as the anticipated N-glycosidically
      linked side chains was revealed. Thus, correlative histochemical and biochemical
      assessments of bindings with lectin probes has provided important new information
      about differences in the glycosylation patterns of individual glycoproteins
      stored within the same secretory granules.

PMID- 8861773
TI  - Facts and paradoxes in current notions of nuclear organization and function.
AB  - Invisible compartments, identified rather by their activities than by their
      morphology, seem to operate in the nucleus. These compartments interrelate
      somehow, including mediation by the nuclear matrix. As our knowledge about the
      nucleus increases, more paradoxes become evident. We here consider some of them:
      1) the well-known C-paradox of Cavalier-Smith, concerning the disproportionate
      amount of nuclear DNA content in comparison with the amount of DNA potentially
      able to transcribe; 2) the DNA folding in the chromatin fibre and its
      superorganization within the nucleus, which seems to be in opposition with the
      transcribing and self-replicating activities; 3) the elusive role of the DNA
      sequences with different degrees of repetitivity; and 4) the compartmentalization
      in the nucleus and how it relates to transcription, processing and transport of
      transcripts, and to DNA reduplication. We conclude by introducing the concept of
      species specific, minimal, but essential genome components, i.e. the elusive few
      thousand DNA bases that, in our hypothesis, act as a functional bridge between
      the nuclear matrix and chromatin.

PMID- 8861774
TI  - Growth factors in mechanisms of malignancy: roles for TGF-beta and FGF.
AB  - Malignant progression is a complex process involving the accumulation of multiple
      genetic alterations leading to changes in many specialized cell functions.
      Important in this process is the loss of growth control which is frequently
      associated with modifications in growth factor production, and growth factor
      response pathways. Indeed, oncogenes have been characterized that code for
      polypeptide growth factors or their receptors, and many tumor cell populations
      release potently mitogenic growth factors which contribute to the malignant
      properties of tumor cells. In this review, the importance of growth factors in
      mechanisms of malignant progression is emphasized, using as examples the
      transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF)
      families. We describe many of the properties and biological activities of these
      two families of growth factors, focusing on mechanisms of autocrine and
      intracrine mitogenic stimulation of tumor cell proliferation and malignant
      progression. The discussion includes evidence for altered growth factor
      expression in tumor cells, and the relationship between these changes in growth
      factors and alterations in the regulation of DNA synthesis, cell proliferation,
      protease production and cell motility required for invasion and metastasis.
      Recent studies are described that show that aberrant expression of TGF-beta1,
      bFGF or K-FGF results in dramatic changes in the genetic stability of cells,
      leading to increased rates of spontaneous gene amplification and the generation
      of drug resistant variants. These findings describe new malignancy relevant
      functions for altered growth factor expression.

PMID- 8861775
TI  - Architecture of the mammalian pituitary cholinergic system with observations on a
      putative blood acetylcholine sensor.
AB  - Acetylcholine (ACh) plays an important role in pituitary gland function. Little
      is known, however, about the source and trajectory of pituitary ACh, the location
      of pituitary cholinergic receptors, and the pathways along which the release of
      pituitary ACh is controlled. Therefore choline acetyltransferase (CHAT)
      immunoreactive profiles have been investigated in the rat median eminence and
      pituitary. Furthermore, both muscarinic- (mAChRp-L) and nicotinic receptor
      proteinlike (nAChRp-L) immunoreactivity have been examined in the rat, rabbit,
      and cat pituitary. The results have demonstrated that the rat pituitary ChAT
      network is composed of neurons in the hypothalamic arcuate nucleus and a great
      number of terminals in the median eminence. In the pituitary, ChAT immunolabeled
      profiles were virtually absent. This suggests that much of the ACh acting on
      pituitary cells is released as a humoral factor from the median eminence. All the
      examined animals expressed mAChRp-L immunostained endocrine cells in the
      intermediate lobe. Apart from this, marked species differences in AChRp-L
      immunolabeled profiles have been found. In addition, strong mAChRp-L
      immunoreactive rod to cone-shaped bodies were detected associated with blood
      vessels of the anterior and intermediate lobes in the rat and rabbit, but not in
      the cat. The immunolabeling was present in particles on the body plasma membrane.
      These characteristics suggest that the function of these structures might be to
      sense pituitary blood ACh levels. Consequently the name blood acetylcholine
      reading bodies (BARBs) was adopted to indicate these structures. It is proposed
      that the BARBs may play a role in the feedback control of ACh release from the
      median eminence.

PMID- 8861776
TI  - Pharmacokinetics of selective serotonin reuptake inhibitors: clinical relevance.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are a safe and effective class of
      drugs for treatment of depressive and obsessive-compulsive disorders. Among this
      class of drugs, pharmacodynamic actions, antidepressant efficacy and adverse
      effect profiles are remarkably similar. However, pharmacokinetic profiles of
      SSRIs are substantially different especially with respect to pharmacokinetically
      mediated drug-drug interactions. For example, fluoxetine and paroxetine produce
      clinically significant inhibition of cytochrome P450 2D6 at their usually
      effective antidepressant dose, whereas citalopram, fluvoxamine or sertraline do
      not. There is also a substantial difference between SSRIs with respect to their
      capacity to inhibit other cytochrome P450 enzymes including IA2, 2C19, 3A4 and
      possibly 2C9/10. The inhibition of these enzymes can reduce the clearance of
      concomitantly administered drugs which are dependent on oxidative metabolism
      mediated by these enzymes as a necessary prerequisite for their subsequent
      elimination. The accumulation of unusually high levels of such drugs can result
      in an increase in nuisance and/or more serious, even life-threatening, adverse
      effects depending on the pharmacology of the co-prescribed drug. Knowledge of
      these issues will enable clinicians to predict and make appropriate dose
      adjustments to avoid potential drug-drug interactions that otherwise could result
      in toxicity.

PMID- 8861777
TI  - Characteristics of the protective action of alpha-Tocopherol in vascular hypoxia.
AB  - The functioning of the guinea-pig isolated portal vein was monitored by measuring
      spontaneous mechanical activity, responses to electrical stimulation and
      administered noradrenaline in normoxic conditions. The effect of hypoxia, induced
      by bubbling the physiological bathing solution with a 95% N(2)/5% CO(2) gas
      mixture, on the mechanical performance of the vein was then assessed. Spontaneous
      activity declined in hypoxia, with mean contraction tension reduced by 55 + or -
      8.8%. The responses to electrical field stimulation (2-32 Hz, 0.7 msec. 70 V)
      were lowered by 14 + or - 4.6% but contractions produced by a range of
      noradrenaline concentrations (0.01-160 mu M) were unaffected by hypoxia.
      Substitution of glucose in the bathing solution with sucrose, a substrate
      unavailable to the cells for energy generation, produced a marked enhancement of
      the effect of hypoxia. Spontaneous activity was reduced by 76 + or - 8.3%,
      electrically-induced activity by 80 + or - 14.4% and noradrenaline-induced
      responses by 85 + or - 6.8%. Although in normoxia the activity and responses of
      the portal vein were unaffected by the presence of alpha-tocopherol, it
      significantly protected the functioning of the vein in hypoxic conditions. This
      effect was concentration-dependent within the range 10-160 mu M and was most
      marked when glucose was replaced by sucrose in the bathing solution.

PMID- 8861778
TI  - Use of rat and human liver slices for the detection of steroid hormone-induced
      DNA-adducts in vitro by means of the (32)P-postlabeling technique.
AB  - Precision cut liver slices from humans and rats were used to investigate the
      covalent binding of xenobiotics to the DNA by means of the (32)P-postlabeling
      technique. Human liver slices were incubated with the structurally related
      steroid hormones chlormadinone acetate (5 mu g/ml), cyproterone acetate (0.01-5
      mu g/ml), megestrol acetate (5 mu g/ml), and the positive control 2-aminofluorene
      (0.01-5 mu g/ml), which is known for its marked ability to form DNA-adducts in
      vivo. Rat liver slices were incubated with cyproterone acetate in concentrations
      of 0.1, 1, and 5 mu g/ml. The functional viability and metabolic activity of the
      slices were shown to be sufficiently maintained during the incubation time by
      measurement of the intracellular K(+)-content and the metabolic turnover of the
      model substrate 7-ethoxycoumarin, respectively. All three test substances and the
      control induced DNA-adducts in human liver slices, however, with a different
      adduct pattern. While the total DNA-adduct levels obtained with cyproterone
      acetate and megestrol acetate were in the same order of magnitude (on average
      1000 DNA-adducts/10(9) nucleotides after incubation with 5 mu g /ml), the
      relative adduct labeling calculated for chlormadinone acetate was about 400.
      Following in vitro incubation of rat liver slices with cyproterone acetate, the
      relative adduct labeling values increased proportionally with increasing
      concentrations and added linearily to in vivo generated DNA-adducts. At the level
      of liver slices, different DNA-adduct patterns were induced by cyproterone
      acetate in rat and man. In contrast to the finding of others, using rat
      hepatocytes, the relative adduct labeling values of cyproterone acetate and
      megestrol acetate were in the same order of magnitude after incubation with human
      liver slices. The present study indicates that liver slices are a useful tool to
      investigate the in vitro DNA-adduct inducing potential of xenobiotics.

PMID- 8861779
TI  - Paracetamol-induced spindle disturbances in V79 cells with and without expression
      of human CYP1A2.
AB  - Spindle disturbing effects in terms of c-mitosis and cytotoxicity of paracetamol
      were investigated in two Chinese hamster V79 cell lines, one of which (V79MZh1A2)
      was transfected with human CYP1A2. This enzyme catalyses the oxidative formation
      of the reactive paracetamol metabolite, NAPQI, believed to initiate hepatoxicity
      by covalent binding to proteins after overdose. In the native V79 cell line
      paracetamol increased c-mitosis frequency in a concentration dependent manner
      from 8.7 + or - 3.5% (control) to 66 + or - 18% at 20 mM. A significant increase
      to 13.3 + or - 3.5% was first seen at 2.5 mM in the native cell line (P<0.05). In
      the V79MZh1A2 cells the concentration-effect curve was slightly shifted to the
      left (P<0.05) with c-mitosis frequency increased to 12.1 + or - 2.6% (P<0.05) at
      1 mM paracetamol. At 5 mM paracetamol the c-mitosis frequency was 14.4 + or -
      5.0% and 19.0 + or - 3.8% in the native and CYP1A2 expressing cell lines,
      respectively (P<0.05). At 20 mM paracetamol the c-mitosis frequency was 61 + or -
      10% in the V79MZh1A2 cells. Cell survival was reduced to approximately 50% at 5
      10 mM paracetamol in both cell lines. At 20 mM paracetamol survival was further
      decreased to 39 + or - 9% in V79MZh1A2 cells only (P<0.05). The present study
      demonstrated that paracetamol may disturb the spindle of dividing cells conveying
      a risk of aneuploidy. The spindle disturbing effect was only slightly enhanced by
      expression of CYP1A2, suggesting that metabolic activation plays only a minor
      role in this genotoxic effect. The reduction of survival mirrored the increase in
      c-mitosis frequency.

PMID- 8861780
TI  - Effects of propionic acid and pravastatin on HMG-CoA reductase activity in
      relation to forestomach lesions in the rat.
AB  - Administration of 4% propionic acid in powdered diet to rats for 12 weeks induces
      severe hyperplastic lesions in the forestomach mucosa. The mechanisms underlying
      this damage are not yet clear. Several lipophilic 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors such as lovastatin and simvastatin
      produce forestomach lesions similar to propionic acid after oral administration
      and the degree of alterations is correlated with their in vitro inhibitory
      potency (Kloss et al. 1991). Therefore it is possible, that sustained inhibition
      of HMG-CoA reductase and induction of hyperplasias may be somehow connected. For
      that reason we investigated, whether or not propionic acid has any influence on
      HMG-CoA reductase activity in vitro and in vivo, because propionic acid has been
      suggested to suppress liver cholesterol synthesis, and also whether or not
      pravastatin, a more polar HMG-CoA reductase inhibitor than lovastatin displays
      similar effects on forestomach mucosa. In untreated forestomach microsomes in
      vitro, propionic acid at a concentration of 51 mM (pH 5.7) inhibited HMG-CoA
      reductase activity by 51 + or - 10%, but at pH 7.2 no inhibition of the enzyme
      could be detected. Furthermore 4% propionic acid-treatment did not lower serum
      cholesterol. In contrast to lovastatin (Kloss et al. 1991), oral administration
      of pravastatin (up to 25% in the diet) did not produce any forestomach lesions in
      the rat. On the other hand, pretreatment with pravastatin revealed that HMG-CoA
      reductase activity in microsomes exceeded the activity of control forestomach and
      liver microsomes by 4.9 fold and 6.7 fold respectively, whereas no induction of
      this enzyme (neither liver nor forestomach) could be observed by pretreatment
      with 4% propionic acid for 12 weeks. Despite increased hepatic HMG-CoA reductase
      activity, pravastatin-treatment significantly lowered serum cholesterol levels of
      rats. These results show that sustained inhibition of HMG-CoA reductase activity
      in forestomach microsomes is not strongly connected with hyperplasia development.

PMID- 8861781
TI  - Arylamine N-acetyltransferase in erythrocytes of cystic fibrosis patients.
AB  - Sulphamethoxazole, a substrate of human arylamine N-acetyltransferase, is used in
      the treatment of cystic fibrosis patients, who metabolise the drug rapidly.
      Increased metabolic clearance of sulphamethoxazole has been suggested to account
      for this rapid metabolism. Arylamine N-acetyltransferase type 1 is expressed in
      erythrocytes and leucocytes and the activity in erythrocytes is shown to
      contribute approximately 99% of the activity of arylamine N-acetyltransferase
      type 1 in blood cells. Arylamine N-acetyltransferase type 1 activity in
      erythrocytes from 16 adult cystic fibrosis patients and 19 age-matched controls
      were compared. Although there is a variation in erythrocyte arylamine N
      acetyltransferase type 1 activity within each group, no difference was found when
      the two groups were compared. All individuals from the cystic fibrosis and
      control groups were investigated for certain allelic variants of the arylamine N
      acetyltransferase type 1 gene (NAT1). Only one copy of a mutant NAT1 allele
      (NAT1*11) was found. The heterozygous NAT1 individual is a cystic fibrosis
      patient with a low level of erythrocyte arylamine N-acetyltransferase type 1
      activity. A second distinct arylamine N-acetyltransferase isozyme, arylamine N
      acetyltransferase type 2, is encoded at the multi-allelic NAT2 locus. There was
      no correlation between erythrocyte arylamine N-acetyltransferase-1 activity and
      NAT2 alleles present in either the cystic fibrosis or control groups. The
      distribution of NAT2 alleles was very similar in the two groups. The increased
      clearance of sulphamethoxazole in cystic fibrosis patients appears unlikely to be
      due to erythrocyte arylamine N-acetyltransferase type 1 activity or to
      inheritance of alleles at either the NAT1 or NAT2 loci.

PMID- 8861783
TI  - Primary alcohols and phosphatidylcholine metabolism in rat brain synaptosomal
      membranes via phospholipase D.
AB  - Phospholipase D of rat brain synaptosomal membranes was tested with
      phosphatidylcholine as the substrate for its specificity in the use of primary
      alcohols as transphosphatidylation co-substrates. The efficiency of the reaction
      was related to the hydrophobicity and the membrane penetrating capacity of the
      alcohol molecule. Phosphatidylalcohol formation could be detected up to 1-octanol
      but not for alcohols with longer hydrocarbon chains (C(9), C(10)). With
      increasing alcohol concentration the transphosphatidylation activity of the
      phospholipase D reached an optimum and then declined abruptly. Alcohol
      concentrations required for maximal transphosphatidylation reaction generally
      decreased with increasing hydrophobicities of the alcohols. Nevertheless 1
      butanol and 4-chloro-1-butanol were the most efficient cosubstrates, sharing
      identical optimal conditions. Transphosphatidylation works at the cost of
      phosphatidic acid formation. Phosphatidic acid itself was transformed to
      diacylglycerol, probably by a contaminating phosphatidic acid phosphohydrolase.

PMID- 8861782
TI  - The involvement of cytochrome P4502E1 in 2-bromoethanol-induced hepatocyte
      cytotoxicity.
AB  - The cytotoxicity of 2-bromoethanol towards hepatocytes isolated from rats was
      concentration-dependent (EC(50)100 mu M, 2 hr). Bromoacetaldehyde was more toxic
      (EC(50)60 mu M, 2 hr) and bromoacetic acid was less toxic (EC(50)150 mu M, 2 hr).
      Glutathione (GSH) depletion occurred before cytotoxicity ensued and GSH depleted
      hepatocytes were more susceptible to 2-bromoethanol. Lipid peroxidation increased
      steadily 1 hr after 2-bromoethanol addition and antioxidants, iron chelators or
      hypoxia prevented 2-bromoethanol induced lipid peroxidation and cell lysis.
      Alcohol dehydrogenase inhibitors, methyl pyrazole or dimethyl sulfoxide only
      partly prevented 2-bromoethanol induced GSH depletion, lipid peroxidation and
      cytotoxicity. However, cytochrome P4502E1 (CYP2E1) inhibitors/substrates were
      more effective at preventing 2-bromoethanol-induced GSH depletion, lipid
      peroxidation and cytotoxicity suggesting that 2-bromoethanol is mostly
      metabolically activated by CYP2E1. Also, hepatocytes isolated from CYP2E1 induced
      rats were more susceptible to 2-bromoethanol and hepatocytes isolated from rats
      pretreated with carbon disulfide to inactivate CYP2E1 were more resistant to 2
      bromoethanol treatment. Formation of S-(formylmethyl)glutathione during 2
      bromoethanol metabolism by microsomal mixed function oxidase in the presence of
      GSH was also prevented by cytochrome P4502E1 inhibitors/substrates or by Anti-Rat
      CYP2E1. Furthermore, aldehyde dehydrogenase inhibitors-cyanamide or chloral
      hydrate increased 2-bromoethanol dependent hepatocyte susceptibility. This
      suggests that 2-bromoethanol is preferably metabolised by CYP2E1 dependent
      monoxygenase to form 2-bromoacetaldehyde which causes cell lysis as a result of
      GSH depletion and lipid peroxidation.

PMID- 8861784
TI  - Agonist and antagonist properties of beta 3-adrenoceptors in human omental and
      mouse 3T3-L1 adipocytes.
AB  - The pharmacological properties of the native human beta 3-adrenoceptor are poorly
      defined. In the present study, the agonist and antagonist properties of beta 3
      adrenoceptors in human omental and mouse 3T3-L1 adipocytes were compared by
      measuring lipolysis in the absence or presence of adrenoceptor blockers.
      Methodological experiments revealed that all three beta-adrenoceptors were
      functionally expressed in both types of adipocytes. This makes the human and the
      mouse cells directly comparable in pharmacological studies. CGP 12177 was a
      selective partial beta 3-adrenoceptor agonist in both cell types with a pD(2) of
      about 7.5. The order of potency of classical non-selective adrenoceptor agonists,
      when determined during blockade of beta 1-, beta 2- and alpha 2-adrenoceptors,
      was isoprenaline>noradrenaline>adrenaline in both human and 3T3-L1 adipocytes.
      This is different from the order of potency of the same agonists at the beta 1-
      or beta 2-adrenoceptors. The sensitivity of the beta 3-adrenoceptor to these
      catecholamines, expressed as pD(2) values, were virtually identical in both
      adipocyte types. Isoprenaline, noradrenaline, and adrenaline were almost full
      agonists in both cell types (intrinsic activity from 74% or 95%) during combined
      beta 1, beta 2- and alpha 2-adrenoceptor blockade. Antagonist potencies
      (expressed as pA(2) and using CGP 12177 as agonist) at the alpha 3-adrenoceptor
      were similar in both adipocyte types: bupranolol>propranolol>metoprolol. The
      corresponding pA(2) values for bupranolol, propanolol and metoprolol were about
      7, 6 and 5, respectively in both species. In conclusion, the pharmacological
      properties of classical catecholamines, beta-adrenoceptor blockers and CGP 12177
      are almost identical at the beta 3-adrenoceptors of human omental adipocytes and
      3T3-L1 adipocytes.

PMID- 8861785
TI  - Interaction of mu-opioid antagonistic drugs with antiepileptics.
AB  - Interactions of the mu-opioid receptor antagonists, naloxone (0.3 and 1 mg/kg),
      cyprodime and clocinnamox (3 and 10 mg/kg for both drugs) with phenytoin (7
      mg/kg), phenobarbital (7 mg/kg), carbamazepine (10 mg/kg) and valproic acid (130
      mg/kg) were investigated using the electroconvulsive threshold in mice as a model
      in order to elucidate a possible role of mu-receptor mediated reactions in the
      mechanism of action of antiepileptic drugs. All 3 mu-antagonists are devoid of an
      effect on the electroconvulsive threshold. Pretreatment with the mu-antagonists
      resulted partly in an increase of anticonvulsant action, partly in a decrease,
      and partly the pretreatment had no effect on the electroconvulsive threshold. The
      anticonvulsant effect of phenytoin was antagonized dose-dependently by naloxone,
      that of phenobarbital by the dose of 10 mg/kg of clocinnamox. A common
      denominator of the mu-antagonistic interactions with anticonvulsants cannot be
      found and the effects observed are therefore considered as "unspecific".

PMID- 8861786
TI  - Trimedoxime and HI-6: kinetic comparison after intravenous administration to
      mice.
AB  - The intravenous pharmacokinetics of the oximes HI-6 (pyridinium-1-(((4-carbamoil
      pyridinio)metoxy)methyl)2 -(hydroxyiminomethyl)dichloride monohydrate), (132.54
      mu mol/kg) and trimedoxime (1,1'-(1,3'-propanedyl)bis((4-hydroxyimino) methyl)
      pyridinium dibromide), (55.98 mu mol/kg) in mice was investigated. The
      concentrations of oximes in plasma determined by high pressure liquid
      chromatography (HPLC) corresponded to a two-compartment pharmacokinetic open
      model. The oximes were rapidly eliminated from mice plasma, with half-times of
      57.93 min. for HI-6 and 108.08 min. for trimedoxime. Although the oximes passed
      from circulation into the tissues at approximately the same rate, their transport
      back to the central compartment was two-times slower in the case of trimedoxime:
      t(1/2k21) was 77.9 min. for trimedoxime and 41.7 min. for HI-6. The total body
      clearance (CI(tot)) of HI-6 was about 25% higher than that of trimedoxime. The
      central compartment volume of HI-6 distribution (V(1)) was greater, whereas the
      volume of distribution of the peripheral compartment (V(2)) was lower for about
      35% with respect to the corresponding parameters of trimedoxime. The calculated
      pharmacokinetic parameters for the oxime HI-6 and trimedoxime show that
      trimedoxime is eliminated more slowly in mice, and penetrates better into the
      peripheral compartment where it remains longer.

PMID- 8861787
TI  - Effect of parasympathetic and sensory transmitters on human epicardial coronary
      arteries and veins.
AB  - Vasomotor effects of various agonists were tested on isolated human epicardial
      coronary arteries and veins at resting tension and after precontraction with
      U46619. Acetylcholine relaxed all arteries with intact endothelium but only some
      endothelium-denuded arteries. Most veins did not relax to acetylcholine. Higher
      concentrations of acetylcholine induced powerful contractions of all arteries and
      veins. Preincubation with atropine significantly lowered the pD(2) values but not
      E(max) values for contractile responses to acetylcholine in arteries and veins
      (pA(2) value for atropine 9.1 arteries and 9.6 veins). Vasoactive intestinal
      peptide, human alpha-calcitonin gene-related peptide and substance P potently
      relaxed all arteries with intact endothelium and all veins. Removal of the
      arterial endothelium abolished relaxation to substance P in most arteries whereas
      responses to vasoactive intestinal peptide were unaffected, and for alpha
      calcitonin gene-related peptide the pD(2) value but not the E(max) value was
      significantly lowered. In both arteries and veins, the antagonists alpha
      calcitonin gene-related peptide (8-37) and spantide lowered significantly the
      potency for alpha-calcitonin gene-related peptide and substance P, respectively,
      without significant changes in E(max) values (pA(2) value for alpha-calcitonin
      gene-related peptide (8-37) 7.9 arteries and 7.9 veins, for spantide 7.6 arteries
      and 8.1 veins).

PMID- 8861794
TI  - Role of neutrophil elastase in the development of renal necrotizing vasculitis.
AB  - To assess the pathogenetic mechanisms of renal vasculitis, we performed
      immunohistochemical studies using renal biopsy specimens which were obtained from
      a patient with microscopic polyangiitis during both the acute and the
      convalescent phase. Intense infiltration and aggregation of neutrophil elastase
      positive (NE+) cells were observed especially in the periglomerular and
      perivascular areas in the first biopsy in which vascular necrosis, rupture of
      Bowman's capsule, and necrotizing glomerulonephritis were present. In addition to
      intracellular NE expression, NE was also expressed extracellularly in both
      segmental glomerular tufts and the interstitium. Intensity of NE immunoreactivity
      in the glomeruli was closely correlated with the development of glomerular
      necrotizing lesions and crescents, but no such correlation was detected with the
      infiltration of macrophages, T cells or B cells. In the second biopsy
      (convalescent phase), patchy intracellular NE expression was present in the
      interstitium, but no aggregation of NE+ cells or extracellular NE expression was
      detected in either the glomeruli or the interstitium. These findings suggest that
      recruitment of polymorphonuclear leukocytes in perivascular and periglomerular
      areas as well as in glomerular tufts, and subsequent extracellular release of NE
      in situ may play an important role in the development of renal vasculitis
      characterized by vascular necrosis, rupture of Bowman's capsule, and tuft
      necrosis.

PMID- 8861795
TI  - Decrease of mesangial matrix after immunosuppressive therapy in children with
      reversible membranoproliferative glomerulonephritis type I.
AB  - We followed the course of membranoproliferative glomerulonephritis (MPGN) type I
      after immunosuppressive therapy in 10 children. At diagnosis all patients had
      abnormal urinary findings. After a mean follow-up of 14 years all but one patient
      showed normal urinalysis and renal function. Glomerular morphometry revealed an
      increase in the ratio of mesangial matrix area to glomerular area (M/G%) in all
      patients. After immunosuppressive treatment, a second biopsy was performed, which
      showed a significantly decreased M/G% in 4 patients. In 3 of the remaining 6, the
      mean M/G% was significantly lower in a third biopsy when compared with the first.
      In addition, there was a negative correlation between M/G% and duration from
      onset disease to biopsy (r = -0.46, p <0.05). Fifteen biopsies (6 initial and 9
      repeat biopsies) were examined for the staining of various extracellular
      matrices. In the initial biopsy type IV collagen, type V collagen and fibronectin
      were increased in expanded mesangial areas. Type III collagen was found
      segmentally in a few biopsies only. M/G% correlated with the grade of type IV
      collagen, type V collagen and fibronectin staining. These findings suggest that a
      reversible clinical course of MPGN type I in children is paralleled by a decrease
      of mesangial matrix expansion.

PMID- 8861796
TI  - Proteinuria and plasma hexosugars in early-stage glomerulonephritis.
AB  - Marked changes in the plasma concentration of several non-glucose monosaccharides
      have been detected among patients++ with end-stage renal disease. To find changes
      specific to renal disease and not caused by a failing urinary excretion, we
      studied the plasma monosaccharide concentration in patients with early-stage
      glomerulonephritis whose renal function was normal or only mildly compromised.
      Plasma mannose, fructose and 1,5-anhydroglucitol (1,5-AG) concentrations were
      measured using gas chromatography/mass spectrometry and isotope-labelled sugar
      standard additions. The daily urinary protein excretion was positively correlated
      with the plasma cholesterol (r = 0.785), mannose (r = 0.550), triglyceride (r =
      0.531 ) and fructose (r = 0.401) concentrations, while the correlation with 1,5
      AG (r = -0.581) was inverse. The correlations were statistically significant. As
      previous studies have revealed a close positive correlation between the plasma
      mannose and glucose concentrations, we calculated the mannose/glucose
      concentration ratio to find out whether the increase in mannose concentration was
      or was not explained by ambient glucose. There was a strong correlation between
      the ratio and the urinary protein excretion (r = 0.704). It is inferred that the
      metabolic syndrome associated with glomerulonephritis and characterised by
      hyperlipidemia also involves a derangement in mannose and 1,5-AG metabolism.

PMID- 8861797
TI  - Detailed study of changes in renal function after conversion from cyclosporine to
      azathioprine.
AB  - The renal dysfunction induced by cyclosporine (CsA) has been demonstrated to be
      at least partially reversible after cessation of CsA therapy. The time course and
      magnitude of changes in various parameters of renal function after CsA withdrawal
      have not been studied in detail. We examined 12 renal transplant patients
      immediately before and 1, 2, and 4 weeks after replacement of CsA by azathioprine
      at 3 months after transplantation. Nine patients in whom CsA was continued during
      this period served as a control group. A significant increase in glomerular
      filtration rate ([GFR] 15 + or - 17%, p <0.01) occurred already in the first week
      after discontinuation of CsA. From 1 to 4 weeks after conversion, GFR did not
      significantly increase any further. A fall in serum creatinine (-7 + or - 9%, Ns)
      paralleled the rise in GFR (r = -0.76, p <0.01), but there was a further decrease
      of creatinine in the second to fourth week after conversion. Withdrawal of CsA
      induced a rise in serum magnesium in all patients (0.73 + or - 0.13 vs 0.86 + or 
      0.12 mmol/l, p <0.001) as well as a marked decrease in the serum level of urate
      (0.39 + or - 0.09 vs 0.33 + or - 0.07 mmol/l, p <0.01) within one week. None of
      the observed changes took place in the control group. In conclusion, a major
      improvement of GFR occurs within one week after cessation of CsA therapy. Changes
      in the serum levels of magnesium and urate appear to be the most responsive
      markers of the renal effects of CsA.

PMID- 8861798
TI  - Obstruction to venous outflow from the left lower extremity after renal
      transplantation.
AB  - Three patients with acute massive swelling of the left lower extremity occurring
      soon after placement of a renal allograft in the left iliac fossa are described.
      In each patient, obstruction to venous outflow from the left lower limb was
      documented by venography. We surmise that venous obstruction resulted principally
      from a combination of extrinsic compression of the left iliac vein by the right
      common iliac artery or by the allograft, and enhanced venous return from the
      allograft.

PMID- 8861799
TI  - The measurement of fingernail creatinine in the differentiation of acute from
      chronic renal failure.
AB  - It is often difficult to distinguish acute renal failure clinically from chronic
      renal failure, especially in patients who do not have records of their medical
      history. Since fingernail creatinine (Ncr) reflects serum creatinine at the time
      of nail formation, it has been suggested that the level of Ncr at the distal tip
      of the fingernail might represent the level of the serum creatinine about four
      months previously. In this study, clipped fingernail specimens from 60 normal
      individuals, 35 patients with chronic renal failure and 33 patients with renal
      insufficiency with rapid onset were analyzed for creatinine by a modified
      alkaline picrate method. The results showed that the Ncr level of the renal
      insufficiency with rapid onset group (69 + or - 12.39 mu mol/100 g nail) was
      similar to that in the normal group (62 + or - 10 mu mol/100 g nail) and
      significantly lower than that in the chronic renal failure group (130 + or - 35
      mu mol/100 g nail, p <0.01). The correlation between Ncr and the serum creatinine
      level obtained four months previously was highly significant (r = 0.895, p
      <0.01). This study confirms that the Ncr measurement is of clinical value in
      differentiating acute from chronic renal failure.

PMID- 8861800
TI  - Serotonin metabolism in patients undergoing hemodialysis.
AB  - To determine the pathogenic role of serotonin (5-HT), we investigated 5-HT
      metabolism in undergoing hemodialysis (HD). Mean value of platelet 5-HT in
      patients undergoing HD was significantly lower than that of normal controls (0.22
      + or - 0.16 pmol/10(5) platelets versus 0.35 + or - 0.13 pmol/10(5) platelets, p
      <0.02). While platelet uptake of 5-HT in normal controls reached a plateau in
      each experiment after incubation with authentic 5-HT for 60 min, platelet uptake
      of 5-HT in patients undergoing HD reached various levels. We found significantly
      lower platelet 5-HT levels in patients with diabetes mellitus (DM) after HD
      compared with those in patients with chronic glomerulonephritis (p <0.05). The
      pathogenic role of serotonergic amplifying mechanism especially in patients with
      DM should be investigated. Second, we investigated plasma 11-dehydro-thromboxane
      B2 (11-DTXB2) levels in patients undergoing HD. Mean level of plasma 11-DTXB2
      concentration in patients after HD was significantly higher than in patients
      before HD (32.8 + or - 17.0 pg/ml versus 23.7 + or - 7.2 pg/ml, p <0.02).
      Increased plasma levels of 11-DTXB2 after HD were regarded as an indication of
      hypercoagulation. Our results provide evidence that several factors such as
      hypercoagulation, heparin, 5-HT uptake of platelet, or causal diseases of renal
      failure could be responsible for the lower platelet 5-HT levels in patients
      undergoing HD.

PMID- 8861801
TI  - Indoxyl-beta-D-glucuronide and 3-indoxyl sulfate in plasma of hemodialysis
      patients.
AB  - The content of indoxyl-beta-D-glucuronide, which has been found in patients'
      plasma as a new indicator of renal failure, logarithmically correlated with that
      of 3-indoxyl sulfate (indican) in the plasma of hemodialysis patients, showing
      another weak correlation with beta(2)-microglobulin content. The content ratio of
      indoxyl-beta-D-glucuronide to 3-indoxyl sulfate (IG/IS) gradually increased
      depending on the duration of hemodialysis treatment. Indoxyl-beta-D-glucuronide
      could be easily dialyzed in the hemodialysis treatment, in contrast to hardly
      dialyzable 3-indoxyl sulfate which bound to plasma proteins. Therefore,
      glucuronide conjugation in indole excretion is favorable for hemodialysis
      patients in that it eliminates indoxyl compounds in blood by hemodialysis.

PMID- 8861802
TI  - Is hepatitis C virus-RNA detection by nested polymerase chain reaction clinically
      relevant in hemodialysis patients?
AB  - We have prospectively studied in hemodialysis (HD) patients the evolution of
      hepatitis C virus (HCV) viremia and the putative relationships between the
      viremia and the biological markers of liver disease. For each of 22 HD patients
      having detectable antibodies to HCV (anti-HCV+), we looked four times for serum
      HCV-RNA by nested PCR (N-PCR), in April and November 1992, November 1993 and May
      1994. We checked the transaminases (Trans) and the gamma glutamyl transpeptidase
      (gamma(GT)) levels on the same day as blood tests for the N-PCR. Abnormal Trans
      or gamma(GT)++ values were considered if they exceeded the upper limit of the
      normal level for our laboratory. Fifteen patients (68%) were intermittently N-PCR
      positive (N-PCR+): 3 patients were N-PCR+ at three determinations, 7 were N-PCR+
      at two determinations and 5 only one time. Two patients (9%) were always N-PCR+
      and five (23%) always negative. No correlation between an abnormal value of
      either Trans or gamma(GT) and viremia was evidenced at successive determinations.
      In conclusion, the majority (68%) of the anti-HCV+ patients had intermittent HCV
      N-PCR+. Among the anti-HCV+ patients, 77% were viremic. Since HCV viremia is
      often transitory and since there is no correlation between N-PCR positivity and
      the increase in Trans or gamma(GT) activities, HCV-RNA detection by N-PCR is
      probably not clinically relevant in anti-HCV+ HD patients.

PMID- 8861803
TI  - Midodrine treatment for patients with hemodialysis hypotension.
AB  - Hypotension is the principal complication of chronic hemodialysis. Autonomic
      insufficiency is thought to be a primary contributing cause of hemodialysis
      hypotension. We treated patients who experience hemodialysis hypotension with
      midodrine, a selective alpha-1 adrenergic pressor agent in an initial effort to
      assess potential efficacy. Twenty-one patients who experienced severe hypotension
      during hemodialysis participated in this study. To qualify, patients had to
      exhibit a fall of > or = 30 mmHg in systolic blood pressure with associated
      clinical symptoms during hemodialysis. The lowest intra- and post-dialysis blood
      pressures were monitored for five consecutive hemodialysis treatment periods
      before receiving midodrine, as a baseline. After the patients were titrated to a
      maintenance midodrine dose, the lowest intra- and post-dialysis blood pressure
      data were again collected for five consecutive dialysis treatments. Hemodialysis
      blood pressures on midodrine treatment were compared to baseline to evaluate the
      effect of midodrine. Midodrine given at a mean treatment dose of 8 mg (range 2.5
      25) significantly increased the mean (+ or - SE) minimal systolic pressure from
      93.1 "+ or - " 3.8 to 107.1 + or - 3.2 mmHg (p <0.01) and elevated the mean
      diastolic pressure from 52.3 + or - 2.9 to 57.9 + or - 2.3 mmHg during
      hemodialysis. Also, the post-dialysis blood pressures (systolic/diastolic) were
      significantly increased from 115.6 + or - 3.1/62.3 + or - 2.1 to 129.9 + or -
      3.9/68.1 + or - 1.7 mmHg (p <0.01 and 0.05, respectively). No apparent clinical
      or laboratory abnormalities were observed. Oral midodrine appears to be a safe
      and effective therapy for the treatment of hemodialysis hypotension.

PMID- 8861804
TI  - Minimal change nephrotic syndrome with cecum adenocarcinoma.
AB  - Membranous glomerulonephritis is the most common glomerular disease associated
      with malignancy, the association of minimal change glomerulopathy with solid
      tumor is still uncommon. We report a 72-year-old man with nephrotic syndrome due
      to minimal change glomerular disease; an accurate seek of underlying malignancy
      revealed a cecum adenocarcinoma. We had a complete remission of nephrotic
      syndrome after surgery of carcinoma.

PMID- 8861805
TI  - Nephrotic syndrome associated with chronic lymphocytic leukemia resistant to
      immunosuppressive drugs: remission obtained by splenectomy.
AB  - Chronic lymphocytic leukemia is a common disease in the elderly but is rarely
      associated with a nephrotic syndrome. The rarity of this association suggests
      that leukemic cells may have certain properties or features that may lead to the
      development of glomerulonephritis. Effective medical treatment of the leukemia
      may not necessarily allow regression of the nephrotic syndrome; however, the
      effects of splenectomy on nephrotic proteinuria when associated to chronic
      lymphocytic leukemia have never been evaluated. We report the case of a 50-year
      old male with stage C CD5+ chronic lymphocytic leukemia associated with a
      nephrotic syndrome due to Type I membranoproliferative glomerulonephritis.
      Chlorambucil and prednisone were unable to control the leukemia and the nephrotic
      range proteinuria, and were discontinued because of poor hematologic tolerance. A
      splenectomy immediately resulted in a spectacular remission of both chronic
      lymphocytic leukemia and the nephrotic syndrome. Spleen lymphocytes were
      collected and tested in quantitative flow cytometry for the expression of the
      main B cell associated markers. They did not exhibit any particular
      immunophenotypic pattern. This report of a remission of a glomerulonephritis
      associated with chronic leukemia following splenectomy is evidence of a possible
      relationship between the two diseases.

PMID- 8861806
TI  - The presentation, treatment and outcome of acute glomerulonephritis in the
      elderly.

PMID- 8861807
TI  - Prevalence of pulmonary tuberculosis in end-stage renal disease (ESRD) patients
      is not unusually high.

PMID- 8861808
TI  - Prolonged intrauterine transabdominal ventricular external drainage. A method to
      decompress dilated fetal ventricles.
AB  - Advances in diagnostic procedures to detect intrauterine hydrocephalus have
      compelled neurosurgeons to intervene in order to preserve precious neural tissue.
      We present the first case (to the best of our knowledge) of a successful decrease
      in intracranial pressure and head circumference by repeated transabdominal
      intrauterine external drainage. The mother tolerated the procedure well. No
      complication occurred from the procedure. This method may temporarily decrease
      the intracranial pressure and head circumference in utero, preserve neural tissue
      and facilitate normal vaginal delivery. The literature of intrauterine
      intervention in hydrocephalic fetuses is reviewed.

PMID- 8861809
TI  - Caudascopic experiences and a new patho-anatomic concept for treatment of
      sciatica.
AB  - In order to investigate the potential of an exclusively endoscopic extradural
      approach as an alternative to open discectomy, epidural endoscopy was performed
      in 5 cadavers. This did not produce satisfactory images of the epidural space.
      Intradural endoscopy (caudascopy) was performed, to show whether additional
      anatomical factors might explain a radicular syndrome supplementary to or without
      a disc herniation. Caudascopy allowed excellent images of the cauda equina, nerve
      roots, and the entrance of the lumbar nerve root sheaths. A Fogerty balloon
      positioned in the intervertebral foramen was used to simulate disc herniation.
      The impact of this simulation on the intradural endoscopic image was observed to
      be minimal. A dural fold was identified at the entrance of the nerve root sheath.
      It is proposed as a factor contributing to the mechanical involvement of
      lumbosacral nerve roots. Pressure measurements in the intradural nerve root
      sheath support this preliminary finding. An endoscopical management of this
      potential patho-anatomy of the nerve root is suggested.

PMID- 8861810
TI  - Endoscopic ventricular fenestration of intracranial fluid cysts.
AB  - The authors report 5 patients with paraventricular or intraventricular fluid
      cysts, successfully treated by fenestration into the ventricular system using a
      neuroendoscopic technique. The series includes three paraventricular malformative
      CSF cysts, a cyst of the velum interpositum and a cystic astrocytoma with small,
      deeply located and unresectable mural nodule. In all cases the endoscopic
      fenestration was the unique treatment and allowed to avoid the definitive
      ventriculoperitoneal shunt. The surgical endoscopic technique and the
      postoperative radiological findings which indirectly confirm the patency of the
      fenestration are discussed. The authors conclude that endoscopic ventricular
      fenestration represents the treatment of choice for most paraventricular and
      intraventricular CSF collections.

PMID- 8861811
TI  - MIN-biopsy of brain tumors: operative technique and histomorphological results.
AB  - MIN-biopsy is defined as an open minimal invasive biopsy, performed by
      microsurgical principles over a small osteoplastic trepanation or bore hole.
      Localization of the lesion is performed by exact calculation using the CT
      topogram. Between 1993 and 1995 ten patients with unknown intracranial lesions
      were operated using the MIN-biopsy approach. Age ranged between 36 to 84 years
      (median age 57.8 years). Patients included five females and five males.
      Histomorphological diagnosis was possible in all cases. Histological diagnoses
      were glioblastoma multiforme in three patients and B-cell malignant lymphoma in
      four cases. Anaplastic astrocytoma was found in one case and the diagnosis of
      metastatic adenocarcinoma was observed in two patients. Complications or
      neurological deterioration were not observed. MIN-biopsy seems to be a safe
      procedure to arrive at exact neuropathological diagnosis of brain tumors. The
      procedure is compared with the established method of stereotactic biopsy by
      review of the literature.

PMID- 8861812
TI  - Ultrasound-guided endoscopic fenestration of the third ventricular floor for non
      communicating hydrocephalus.
AB  - Conventional valve shunting for treatment of hydrocephalus has a high rate of
      long-term complications. Endoscopic ventriculostomy by fenestration of the third
      ventricular floor, a minimally-invasive technique, avoids many of the drawbacks
      of extracranial shunting. Endoscopy was performed in 12 hydrocephalic patients
      with MRI-diagnosed aqueductal stenosis and neurological signs. Intraoperative
      ultrasound guidance allowed aiming the tip of the rigid endoscope to the foramen
      of Monro, and direct entering of the enlarged third ventricle. This technique is
      as exact as stereotaxy but is faster and easier. No complications were seen due
      to the surgical procedure. Nine patients were cured from their complaints, in 3
      cases there was a subjective improvement of neurology. Long-term patency of the
      third ventriculostomy was confirmed by movement-sensitive MRI.

PMID- 8861813
TI  - Effect of Gamma Knife surgery on the risk of rupture prior to AVM obliteration.
AB  - The incidence for hemorrhage in non-obliterated arteriovenous malformations (AVM)
      during the first two years following Gamma Knife (GK) surgery was compared to the
      calculated incidence in untreated patients. There was a decrease in the incidence
      of hemorrhage as compared to the natural course. This difference was
      statistically significant. The actual number of hemorrhages during the first two
      years was 49 in a series of 1604 patients. Additionally, 41 hemorrhages occurred
      beyond the two years following treatment over the entire follow up time span of
      up to 24 years. For the first two years the calculated incidence was roughly two
      times higher than the observed incidence. This impact on the natural history was
      detectable already within six months after the treatment for the malformations
      totally covered with at least 25 Gy. The relation between a high minimum and a
      high average dose on the one hand and a lower risk for hemorrhage on the other
      hand was statistically significant. Low treatment doses and high age correlated
      to a higher risk. Neither hemorrhage prior to treatment nor time interval between
      presenting hemorrhage and treatment seemed to influence the risk for post
      treatment hemorrhage. The risk for permanent neurological deficit or death due to
      AVM rupture during the latency period between the time of treatment and total
      nidus obliteration was less than 0.5% for small AVM and 2-4% for large ones
      during the first two years. Of the 24 patients with sequelae following AVM
      rupture after treatment 14 died and 10 remained with neurological deficit of
      different degrees. However, all survivors were self sufficient.

PMID- 8861814
TI  - Transvenous embolization of traumatic carotid cavernous fistula with mechanical
      detachable coils.
AB  - An attempt at transarterial balloon embolization of a traumatic carotid cavernous
      fistula was made but the carotid artery rent was too small for this approach. The
      patient was then treated by antegrade embolization through a superior ophthalmic
      vein using mechanical detachable coils. Successful obliteration of the fistula
      was achieved with preservation of the carotid artery. Transvenous embolization is
      an alternative technique to treat patients with traumatic carotid cavernous
      fistulas, especially when a transarterial approach has failed.

PMID- 8861816
TI  - Pharmacological induction of rhythmical activity and plateau action potentials in
      unmyelinated axons.
AB  - The physiological function of the axon is to conduct short all-or-none action
      potentials from their site of initiation (usually the cell body) to the synapse.
      To ensure this function, both passive and active biophysical properties of the
      axons are tuned very precisely, especially the voltage-dependent ionic
      conductances to sodium and potassium. Under normal conditions, axons are not
      spontaneously active. Minor modifications of their ionic micro-environment or
      slight changes in the membrane properties are however sufficient to induce
      rhythmical activity and modify the time course of the action potentials. These
      modifications can be induced by a variety of pharmacological agents. Some typical
      examples taken from original studies on invertebrate preparations are
      illustrated. The experiments were carried out on two axonal preparations: the
      giant axon of the squid Loligo forbesi and the giant axon of the cockroach
      Periplaneta americana. The axons were 'space-clamped' and studied under both
      current-clamp and voltage-clamp conditions. Voltage-clamp experiments were used
      to dissect out the mechanisms underlying repetitive activity and to extract the
      relevant parameters. These parameters were then used to rebuild the observed
      effects using an extended version of the Hodgkin and Huxley (1952, J Physiol
      (Lond) 117, 500-544) formulation. One easy way to get repetitive firing in both
      preparations is to reduce potassium conductance. The effect of 4-aminopyridine on
      squid axon is illustrated here. The experimental results, including the
      occurrence of bursts of activity, can be described by adding a time- and voltage
      dependent block of the potassium channels to the original Hodgkin and Huxley
      (1952, J Physiol (Lond) 117, 500-544) model. Repetitive spike activity and
      plateau action potentials are also produced when the depolarising effect of the
      voltage-dependent potassium current is counterbalanced by a maintained inward
      sodium current. This maintained sodium current can be due to several different
      mechanisms. This will be illustrated by five structurally unrelated molecules:
      two scorpion toxins, two insecticide molecules and one sea anemone toxin. One
      toxin purified from the venom of the scorpion Buthotus judaicus (insect toxin 1)
      exerts its effects by shifting the sodium activation curve towards more
      hyperpolarized potentials. Another toxin purified from the venom of another
      scorpion Androctonus australis (mammal toxin 1) modifies a significant proportion
      of normal (fast) sodium channels into slowly activating and inactivating sodium
      channels. The main effect of the insecticide DDT is to maintain sodium channels
      in the 'open' configuration. Another insecticide molecule known to induce
      repetitive activity, S-bioallethrin, activates voltage-dependent sodium channels
      with slow activation and inactivation kinetics. The sea anemone toxin
      anthopleurin A, purified from the venom of Anthopleura xanthogrammica, delays
      inactivation of the sodium current without changing its activation kinetics.
      These examples show that minor modifications of the properties of the nerve
      membrane are sufficient to alter nerve function. These deleterious effects will
      be amplified at the synapse through dramatic changes in transmitter release and
      will lead eventually to disastrous alterations of brain function.

PMID- 8861817
TI  - Model experiments on squid axons and NG108-15 mouse neuroblastoma x rat glioma
      hybrid cells.
AB  - Three types of ionic current essentially determine the firing pattern of nerve
      cells: the persistent Na+ current, the M current and the low-voltage-activated
      Ca(2)+ current. The present article summarizes recent experiments concerned with
      the basic properties of these currents. Keynes and Meves (Proc R Soc Lond B
      (1993) 253, 61-68) studied the persistent or steady-state Na+ current on dialysed
      squid axons and measured the probability of channel opening both for the peak and
      the steady-state Na+ current (PF(peak) and PF(ss)) as a function of voltage.
      Whereas PF(peak) starts to rise at -50 mV and reaches a maximum at +40 to +50 mV,
      PF(ss) only begins to rise appreciably at around 0 mV and is still increasing at
      +100 mV. This differs from observations on vertebrate excitable tissues where the
      persistent Na+ current tums on in the threshold region and saturates at around 0
      mV. Schmitt and Meves (Pflugers Arch (1993) 425, 134-139) recorded M current, a
      non-inactivating K+ current, from NGI08-15 neuroblastoma x glioma hybrid cells,
      voltage-clamped in the whole-cell mode, and studied the effects of phorbol 12,13
      dibutyrate (PDB), an activator of protein kinase C (PKC), and arachidonic acid
      (AA). PDB and AA both decreased I(M), the effective concentrations being 0.1-1 mu
      M and 5-25 mu M, respectively; while the PDB effect was regularly observed, the M
      current depression by AA was highly variable from cell to cell. The PKC 19-31
      peptide, an effective inhibitor of PKC, in a concentration of 1 muM almost
      totally prevented the effects of PDB and AA on M current, suggesting that both
      are mediated by PKC. Schmitt and Meves (Pflugers Arch (1994a) 426, Suppl R 59)
      measured low-voltage-activated (l-v-a) and high-voltage-activated (h-v-a) Ca2+
      currents on NG108-15 cells and investigated the effect of AA and PDB on both
      types of current. At pulse potentials > -20 mV, AA (25-100 mu M) decreased 1-v-a
      and h-v-a I(Ca). The decrease was accompanied by a small negative shift and a
      slight flattening of the activation and inactivation curves of the l-v-a I(Ca).
      The AA effect was not prevented by 50 mu M eicosa-5,8,11,14-tetraynoic acid
      (ETYA), an inhibitor of AA metabolism, or PKC 19-31 peptide and not mimicked by
      0.1-1 mu M PDB. Probably, AA acts directly on the channel protein or its lipid
      environment. The physiological relevance of these three sets of observations is
      briefly discussed.

PMID- 8861818
TI  - Modulation and dynamic specification of motor rythm-generating circuits in
      crustacea.
AB  - The operation of central pattern generators (CPGs), oscillatory neural circuits
      responsible for rhythmic motor behavior, is now known to depend both on the
      synaptic interactions between constituent neurons and their intrinsic membrane
      properties (oscillatory, plateauing, etc). Moreover, these synaptic and cellular
      properties are not invariant, but are subject to a wide range of neuromodulatory
      influences that, by modifying the bioelectrical character of individual neurons
      and/or the strength of their synapses, are able to adapt the output of a given
      CPG circuit to the changing needs of the animal. Despite this ability to produce
      different functional configurations, however, the assumption remains of a CPG as
      a predefined assemblage of interconnected neurons dedicated to a particular
      behavior and functionally distinguishable from other circuits responsible for
      other tasks. However, our recent studies on the stomatogastric nervous system
      (STNS) of crustacea have begun to question this concept of the CPG as a discrete
      and identifiable entity within the central nervous system. Here we review
      evidence showing that under neuromodulatory instruction, individual neurons can
      participate in different oscillatory motor circuits and hence more than one
      rhythmic behaviour, and even more profoundly, preexisting networks can be
      dismantled to specify dynamically a new circuit for an entirely different
      behaviour. This de novo network construction is achieved again by neuromodulatory
      induced alterations in the oscillatory and synaptic properties of individual
      target neurons. On this basis, therefore, a functional CPG network must be seen
      in a more dynamic context than previously thought since it may exist only in a
      particular behavioural situation dictated by modulatory influences.

PMID- 8861819
TI  - Cholinergic control of the walking network in the crayfish Procambarus clarkii.
AB  - The output of a neuronal network results generally from both the properties of
      the component neurons and their synaptic relationships. This article aims at
      synthesizing various results obtained on the neural network generating locomotion
      in vitro. In the preparation used, consisting of the last three thoracic ganglia
      (3-5) along with motor nerves from the 5th leg ganglion to the promotor, remotor,
      levator and depressor muscles, motor nerve recordings generally revealed only
      tonic activity in several different motoneurons (MNs). However, rhythmic activity
      can be obtained by the use of cholinergic agents such as the oxotremorine (Oxo)
      superfused in the bath (5 x 10(-5) M). If Oxo is pressure-ejected locally in the
      ganglion, it is possible, depending upon the locus where the drug is applied, to
      elicit a rhythmic activity restricted to a group of antagonistic MNs. To analyze
      how cholinergic agents are able to induce such rhythmic activity, very small
      volumes of drug (50-200 pl), were applied close to the recording electrode. Two
      types of depolarizing response occurred: a fast large amplitude depolarization (5
      20 mV) and a long lasting (10s to several minutes) low amplitude depolarization
      (1-3 mV). These responses persisted in the presence of TTX and Co(2)+. The
      transient initial depolarization is a mixed nicotinic and muscarinic voltage
      independent response during which the input resistance decreases by 20 to 40%. In
      contrast, the long lasting component is voltage-dependent, exclusively muscarinic
      and associated to a 5-10% increase of input resistance due to the closing of a K+
      conductance that is active at the resting Vm, and totally suppressed at holding
      potentials below -70 mV. More generally, K+ currents activated at resting
      potential are responsible for membrane potential stability. The injection of TEA,
      a blocker of the K+ currents, through the recording electrode is able to unmask
      plateaus above a threshold depolarization. These plateaus are TTX-sensitive but
      persist in the presence of Ca(2)+ channel blockers. Moreover, in 10% of TEA
      filled MNs a spontaneous pacemaker activity was revealed. The organization of the
      locomotor network is also based upon connections between MNs and INs. Within a MN
      pool, connections are only loosely established, appearing to consist mainly of
      electrical coupling. Inhibitory synaptic connections between MNs of opposite
      pools are mediated by chloride channels. However, the neurotransmitter involved
      could be either GABA or glutamate. Therefore, at the level of a given joint, a
      basic rhythm occurs due to both motoneuronal membrane properties and motoneuronal
      connectivity. However, the coordination of all MNs of an entire leg during
      fictive walking activity requires the involvement of INs. Based upon these data,
      we propose a two-stage model of the locomotor network organization: a joint
      motoneuronal level and a whole leg interneuronal level.

PMID- 8861820
TI  - The neuronal network for locomotion in the lamprey spinal cord: evidence for the
      involvement of commissural interneurons.
AB  - The spinal cord of the lamprey, a primitive vertebrate, has been used as a model
      system for investigating the cellular basis of rhythmic locomotor activity. Three
      classes of interneurons have been characterized that are active during locomotor
      activity in the isolated spinal cord (ie fictive swimming). The identified
      synaptic interactions of these neurons form a network which has been proposed to
      underlie locomotor rhythmogenesis. Modeling studies confirmed that the network
      can produce oscillatory activity with phase relations among the neurons similar
      to those found in the spinal cord. Within the network, inhibitory commissural
      interneurons form reciprocal inhibitory connections and play a key role in
      rhythmogenesis. Several experiments have been done to test whether these cells
      participate in the generation of rhythmic activity in the spinal cord. First,
      midline lesions that sever the axons of commissural interneurons eliminate
      rhythmic ventral root bursting. Second, photo-ablation of commissural
      interneurons on one side of the spinal cord alters the symmetry of ventral root
      bursts, alters the cycle period, and can eliminate rhythmic bursting. Taken
      together, these experiments support the model that commissural interneurons are
      involved in rhythmogenesis in the lamprey spinal cord.

PMID- 8861821
TI  - Inhibition of crossed caudal interneurons by lateral interneurons in lamprey
      spinal chord during fictive locomotion.
AB  - Templates of the membrane potential profiles from lateral (LI) interneurons and
      motoneurons during glutamate- and N-methyl-D-aspartate (NMDA)-induced fictive
      locomotion showed pronounced plateau phases. In contrast, crossed caudal (CC)
      interneurons had a less obvious and steeper plateau region that was followed by a
      clear notch coinciding with the end of the lateral interneuron plateau phase.
      These results indicate a significant inhibitory input from LI to CC interneurons.

PMID- 8861822
TI  - Positive feedback as a general mechanism for sustaining rhythmic and non-rhythmic
      activity.
AB  - Our aim is to reassess our proposal that various states of motor output may be
      sustained by positive feedback generated within the premotor neural circuitry.
      The evidence for this proposal came from the Xenopus embryo which when touched
      can swim for many seconds even after all movement has been prevented by a
      neuromuscular blocking agent. Experiments showed that even the spinal cord could
      sustain its own swimming activity for a few seconds after stimulation. We
      proposed that this was the result of the glutamatergic excitatory spinal
      interneurons synapsing with each other. Because this excitation is of long
      duration compared to the swimming cycle period it can sum from cycle to cycle to
      sustain swimming by a form of positive feedback. We have tested the plausibility
      of these ideas by making realistic computer simulations of the spinal networks
      and have shown that positive feedback can sustain stable swimming activity.
      Pharmacological evidence recently suggested that acetylcholine contributes to the
      excitation underlying swimming in spinal embryos so we investigated the central
      synapses made by motoneurons. Recordings from pairs of synergistic motoneurons
      then showed: a) cholinergic chemical synapses from more rostral motoneurons
      activate nicotinic receptors and produce excitation; and b) local intrasegmental
      electrical synapses also lead to mutual excitation. The presence of central
      motoneuron synapses suggested that they could contribute to excitation during
      swimming. We therefore used local drug applications to see if spinal neurons
      received cholinergic or electrical excitation during fictive swimming. The
      results show that motoneurons received both types of excitation while
      interneurons received only cholinergic excitation. This evidence suggests that
      when motoneurons are active during swimming they contribute positive feedback
      excitation not only to themselves but also to the premotor interneurons of the
      spinal rhythm generating network. This excitation would sum with that from
      'glutamatergic' excitatory interneurons. We conclude that in addition to our
      original proposal of feedback between excitatory interneurons, there are other
      forms of positive feedback during swimming in the Xenopus embryo spinal cord.
      Motoneurons feed excitation back to each other. They may also contribute
      cholinergic excitation to premotor interneurons which could sum with the
      excitation from 'glutamatergic' interneurons and help to sustain swimming. If
      they do this, motoneurons may be a component part of the central pattern
      generator for swimming. Since central motoneuron synapses are a feature of most
      vertebrate groups, these results suggest a reevaluation of such synapses in these
      groups also.

PMID- 8861823
TI  - Do cortical and thalamic bioelectric oscillations have a functional role? A brief
      survey and discussion.
AB  - This paper first briefly describes rhythmic bioelectric oscillations that can be
      recorded from the neocortex (particularly in cats). This descriptive section is
      followed by a review of the mechanisms whereby these rhythms are generated, and a
      section in which we try to go beyond the purely correlative aspect and discuss
      the possible functional role of synchronized oscillations in thalamo-neocortical
      channels. Based on the literature data, it seems that two distinct and opposite
      roles can be attributed to these oscillations: either to lower the level of
      awareness, such as in slow wave sleep, when these oscillations are widespread on
      the neocortex; or to contribute to perceptual processing, when these rhythms are
      more localized and possibly of a higher frequency. Electrocortical (ECoG)
      rhythmical activities have been known and described since the early days of
      electrophysiological explorations of the human and animal brain. Surprisingly
      though, little importance has generally been attached to these oscillatory
      activities, except as indicators of sleep stages in animals and humans and, in
      the case of the alpha rhythms (the first rhythm to be discovered in the thirties
      by Hans Berger), of a certain state of 'relaxation' in humans. Despite the well
      accepted fact that the human alpha rhythm evidently occurs during waking (even if
      it is in a 'relaxed' state), the idea has curiously prevailed that the waking
      ('aroused') state in general is mostly characterized by low voltage fast
      ('desynchronized') activity. It is only more recently that some studies have
      suggested a functional importance of a variety of regular oscillatory activities
      that can be recorded from the neocortex and/or from a variety of thalamic nuclei
      not only in the sleeping but also on the waking, behaving animal. This review
      considers possible reasons indicating that these rhythmical activities are more
      than just epiphenomena. Our analysis is essentially restricted to the cat, with
      only a very quick glance at other species.

PMID- 8861824
TI  - Spatio-temporal characteristics of paroxysmal interictal events in human temporal
      lobe epilepsy.
AB  - A spatio-temporal mapping technique was applied to stereotactically-implanted
      depth electrode recordings (SEEG). This technique was used to study the
      interictal activity in 13 epileptic patients with temporal lobe epilepsies during
      the pre-surgical evaluation of their epileptogenic zone prior to surgery. The
      method further provided the precise localization of distinct interictal
      activities in each explored structure. The high sensitivity of the technique is
      showed and has demonstrated the evidence of multiple sources during one single
      sequence of interictal activity. The stability of such an activity was also
      demonstrated in each patient. A temporal relationship existed between the
      activity recorded in different structures. Paroxysmal interictal activity thus
      appeared as an ordered and successive activation of different interictal loci
      overlapping each other. In this way it was possible to distinguish two different
      types of activities: primary foci that are activated independently of each other,
      and secondary foci activated by the primary foci. Finally, in addition to the
      source localization of interictal activity, the problem of detection and
      discrimination of the different components must be considered.

PMID- 8861826
TI  - Alglucerase (Ceredase).

PMID- 8861825
TI  - Pharmacotherapy of opioids: present and future developments.
AB  - The clinically available opioids have different physicochemical properties,
      resulting in differences in clinical profile with regard to potency, onset, and
      duration of activity. However, they all have comparable side-effects after acute
      systemic application. Several approaches can be used to overcome these side
      effects. The following approaches, with special emphasis on the perioperative use
      of the opioids, are discussed: (1) the use of alternative routes of
      administration, such as via the spine (epidurally and intrathecally); (2)
      optimization of opioid delivery by means of slow-release preparations, chronic
      infusions with indwelling catheters, and transdermal delivery systems; (3) use of
      additional agents to potentiate the analgesic properties of the opioids so that
      the dose of opioid can be reduced; and (4) searching for new analgesics on the
      basis of knowledge of the pain-transmission system and the different opioid
      receptors with their functional interactions.

PMID- 8861827
TI  - 3(3) factorial design-based optimization of the formulation of nitrofurantoin
      microcapsules.
AB  - A microcapsule form of nitrofurantoin was prepared by a simple coacervation
      method with carboxymethylcellulose and aluminium sulfate. 3(3) factorial design
      was performed for three independent variables, namely, the particle size of the
      drug, the size of the microcapsules and the pH of the dissolution medium. The
      dissolution tests with the formulated microcapsules were carried out according to
      the United States Pharmacopeia XXII rotating basket method at pH 1.2, 5, and 7.5,
      which represent the pH of gastrointestinal fluids. Release data were examined
      kinetically and the ideal kinetic models were estimated and t(63.2) values
      obtained from RRSBW distribution were used in the factorial design experiment.
      The influence of the independent variables on the dissolution of nitrofurantoin
      microcapsules could be expressed as the pH of the dissolution medium > particle
      size of the microcapsule > particle size of nitrofurantoin. The other aim of this
      study was to evaluate microcapsule formulation in terms of the United States
      Pharmacopeia criteria with a minimum of experiments. Our findings suggest that
      dosage forms which comply with the pharmacopoeia criteria for dissolution can be
      prepared and selected by factorial design.

PMID- 8861828
TI  - Rectal administration of paracetamol: a comparison of a solution and
      suppositories in adult volunteers.
AB  - The pharmacokinetics and tolerability of two dosage forms for rectal
      administration of paracetamol were compared. A fatty suppository was compared
      with a solution of 60 mg/ml paracetamol. Both dosage forms were given as 1000 mg
      doses to 10 healthy adult volunteers. The solution produced peak plasma
      concentrations significantly faster (t (max)) than did the suppository. The peak
      concentration (C(max)) and the area under the curve (AUC(6)) were also
      significantly greater. The pharmacokinetic characteristics of the solution were
      superior to those of the suppository. No difference in irritation score was
      identified and no discomfort was reported.

PMID- 8861829
TI  - Safety of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in patients with human
      immunodeficiency virus infection: a pilot study.
AB  - The compound 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent inhibitor of
      a number of viruses in vitro such as human immunodeficiency virus types 1 and 2,
      herpes simplex virus types 1 and 2, hepatitis B virus, cytomegalovirus, and
      Epstein-Barr virus. PMEA also proved to be effective in vivo against feline
      immunodeficiency virus in cats and simian immunodeficiency virus in rhesus
      monkeys. In an open, non-placebo-controlled trial, the safety of weekly doses of
      PMEA in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS
      related complex was studied for a period of 11 weeks. CD4+ T-cell counts at
      baseline were between 10 and 450/mm(3). The drug was administered intravenously
      at a dose of 1000 mg. No serious side-effects were seen. On one occasion one
      patient showed alanine aminotransferase and aspartate aminotransferase levels 5
      times higher than the upper limit of normal and another patient showed on one
      occasion aspartate aminotransferase levels 5 times higher than the upper limit of
      normal. In another patient serum amalyse levels increased, on one occasion 1.5
      times above the upper limit of normal. An improvement in general well-being was
      reported by all patients. For patients with a CD4+ T-cell count > 100/mm(3) at
      baseline, the CD4+ T-cell count increased from a mean of 283/mm(3) at baseline to
      a mean of 448/mm(3) at the end of the study. Repeat infusions of PMEA at a dose
      of 1000 mg were safe and well tolerated. Our results suggest that PMEA,
      administrated according to this treatment schedule, may be effective in treating
      patients with human immunodeficiency virus infection.

PMID- 8861830
TI  - The efficacy of Prrrikweg gel in the treatment of insect bites: a double-blind,
      placebo-controlled clinical trial.
AB  - OBJECTIVE: This study was conducted to examine the efficacy of Prrikweg gel, a
      homeopathic after-bite gel, in relieving the effects of mosquito bites, in
      particular itching and erythema. DESIGN: A double-blind, randomized, placebo
      controlled clinical trial. SETTING: London School of Hygiene and Tropical
      Medicine. SUBJECTS: 100 healthy volunteers. METHODS: All subjects were bitten
      under laboratory conditions by Aedes aegypti mosquitoes at one spot on the
      ventral aspect of the left forearm and another on a corresponding position on the
      right forearm. One spot was treated with the homeopathic after-bite gel and the
      other with a placebo gel. MAIN OUTCOME MEASURES: Itching was assessed on a 5
      point discrete rating scale at 0, 0.5, 1, 26.5, and 48 h post-bite to compare the
      itch-relieving efficacy of the two treatments. Erythema development was assessed
      by photographing the bite sites, measuring length and width of the erythema with
      a calliper, and comparing the ratio of the erythema surface at baseline T(0) to
      the mean erythema surface at 0.5, 1, 26.5, and 48 h post-bite (T mean) for the
      two treatments. RESULTS: Testing erythema development by comparing the ratio
      T(0)/T (mean, after-bite gel) and the ratio T(0)/T (mean, placebo gel) gave a two
      tailed p = 0.098(95% Cl, -0.031-0.361) in favour of the after-bite gel. There was
      not a statistically significant difference between the itch relief provided by
      the two treatments (two-tailed p = 0.424; 95 percent Cl, -0.541-0.191). The
      correlation between itching and erythema was significant (r = 0.46; p < 0.001).
      CONCLUSIONS. There are strong indications that the homeopathic after-bite gel
      reduces erythema development following mosquito bites. The homeopathic mother
      tinctures of Echinacea angustifolia DC., Ledum palustre L., Urtica urens L. as
      well as the Hamamelis extract in this gel, whether alone or in combination, are
      the biologically active ingredients. The homeopathic after-bite gel was not
      demonstrated to relieve itching; however, based on the correlation between
      erythema and itching, an effect on itching is not inconceivable.

PMID- 8861831
TI  - Psychotropic drug use in a group of Dutch nursing home patients with dementia:
      many users, long-term use, but low doses.
AB  - The aim of this study was to describe the use of psychotropic drugs in a
      psychogeriatric nursing home, "Joachim en Anna", in Nijmegen, the Netherlands. To
      this end the medical records of 890 nursing home patients with dementia, admitted
      between 1980 and 1989, were analysed retrospectively. Each time pattern of
      psychotropic drug use was registered. Drugs were coded by means of the Anatomical
      Therapeutic Chemical classification system. The daily dose was expressed as the
      ratio of the mean prescribed daily dose and the defined daily dose. Side-effects
      and changes in prescription patterns throughout the years patients were admitted
      were analysed. A total of 3,090 time patterns of exposure to psychotropics were
      registered. Neuroleptics, benzodiazepines, and antidepressants accounted for 58,
      32, and 9 percent of the time patterns, respectively. For almost every drug
      prescription the prescribed daily dose was lower than the defined daily dose.
      More than 75 percent of these nursing home patients had at least one prescription
      for a psychotropic drug during institutionalization. One or more side-effects
      were observed in 50 percent of the patients who used a neuroleptic. The total
      number of patients receiving psychotropics did not change throughout the study.
      Psychotropics were prescribed for long-term use, but in a low dose. Side-effects
      were frequently observed while the correct individual dose was being determined.

PMID- 8861832
TI  - A second trefoil protein, ITF/hP1.B, is transcribed in human breast cancer.
AB  - Trefoil proteins form a specific group of stable secreted polypeptides. They are
      expressed in a lot of human cancers and during inflammatory processes of the
      gastrointestinal tract. Recently a new human trefoil protein, ITF/hP1.B, was
      isolated. Until now no studies of the activity of this gene in human solid tumors
      exist. In our examination we show for the first time that this gene is
      transcribed in human breast cancer. In contrast to another trefoil protein, pS2,
      the expression of ITF/hP1.B is not under control of estrogen in the human breast
      cancer cell line MCF-7. We suggest that the gene activity of ITF/hP1.B in
      addition to pS2 expression may be an improved prognostic marker in human breast
      cancer.

PMID- 8861833
TI  - Age-specific sensitivities of mammographic screening for breast cancer.
AB  - The sensitivity of the mammographic screening test in the biennial screening
      program of Nijmegen is assessed by analyzing the occurrence of interval cancers,
      i.e. cancers surfacing clinically in the interval between a negative screening
      examination and the subsequent scheduled examination. The difference between the
      observed number of interval cancers and the expected number of clinically
      manifest cancers in the absence of screening for the interval period reflects the
      number of cancers detected by screening. The expected number should be limited by
      the number of those cancers that were not detectable at the time of the screening
      examination because their size was under the threshold of mammographic
      detectability (5 mm). In contrast to other sensitivity studies we took these
      'fast growing' cancers into consideration, the numbers of which are estimated in
      each of the six-month periods of the two-year interval using age-specific tumor
      volume growth rates for three age groups: < 50, 50-69, and > or = 70 years. In
      patients under age 50, the sensitivity was 64% for cancers which would become
      clinically manifest within one year after screening. This sensitivity was lower
      than those obtained from the 50-69 and > or = 70 age groups, being 85% and 80%,
      respectively. For cancers that would become clinically manifest 12-18 months
      after screening, sensitivity decreases to 22% in the under age 50 group, and to
      56% and 65% in the two above age 50 groups, respectively. We conclude that even
      when adjusted for growth rate, the mammographic screening test has a poor
      performance in the under age 50 group.

PMID- 8861834
TI  - Breast self-examination and survival from breast cancer: a prospective follow-up
      study.
AB  - A prospective study was conducted to investigate the possible effect of breast
      self-examination (BSE) on cause-of-death-specific survival rate of breast cancer
      patients. Six hundred and four breast cancer patients diagnosed in 1984-1986 in
      Finland, and applying for breast prostheses, were interviewed about both their
      BSE practices prior to cancer diagnosis and the actual method of tumor detection.
      No clear differences were observed in the stage distribution or cause of death
      specific five-year survival rates between individuals with different BSE
      practices. After adjustment for potential confounders in the Cox proportional
      hazards analysis, no differences in risk of breast cancer death were observed for
      those who performed BSE monthly as compared to those who practised BSE less
      frequently or not at all. When the method of detection was taken into account, it
      turned out that only 34 (7.6 %) of the 448 regular BSE practisers had actually
      detected their cancers by means of BSE. Furthermore, no survival advantage was
      associated with detection of breast cancer by means of BSE. Those BSE practisers
      whose cancer was detected by BSE had a similar or slightly worse prognosis
      compared to BSE practisers whose cancer had been detected by other means. Our
      results suggest that BSE practice is not beneficial in terms of breast cancer
      survival, nor is detection of breast cancer by means of BSE. Conclusive evidence
      should, however, be obtained from prospective randomized studies of breast cancer
      mortality.

PMID- 8861835
TI  - Bioelectrical impedance for monitoring the efficacy of lymphoedema treatment
      programmes.
AB  - The treatment of lymphoedema includes a combination of massage, compression
      bandaging, and exercise. To date the most common technique of assessing the
      efficacy of treatment has involved estimating the total limb volume from
      circumferential measurements at fixed intervals along the limb. This study
      investigated the application of multiple frequency bioelectrical impedance
      analysis, MFBIA, to monitor the volume of lymphoedema in the upper limb of
      patients who developed this disorder following surgery for cancer of the breast.
      Daily measurements of both circumference and impedance of both the affected and
      unaffected limbs were recorded for 20 patients throughout their 4 week treatment
      programmes. Twenty control subjects were also monitored daily over a similar 4
      week period. Prior to the commencement of treatment the bioimpedance technique
      detected a significant (P < 0.01) asymmetry between the two limbs of the control
      subjects, associated with handedness (P < 0.001). Circumferential estimates of
      limb volumes in the control group detected no asymmetry. Impedance measures of
      extracellular fluid showed all of the patients to lie outside the 95% confidence
      interval determined from the data of the control group. The trends of the
      impedance measures and the circumferential estimates of volume throughout the 4
      week program were found to be significantly different (P < 0.05); MFBIA
      exhibiting a greater sensitivity in the detection of lymphoedema. The results
      demonstrate that MFBIA is significantly more sensitive than circumferential
      measurement both in the early diagnosis of lymphoedema and in monitoring change.

PMID- 8861836
TI  - Cytogenetic abnormalities in an in situ ductal carcinoma and five
      prophylactically removed breasts from members of a family with hereditary breast
      cancer.
AB  - Short-term cultures of tissue samples from three bilateral prophylactic
      mastectomies and one in situ ductal carcinoma from four women belonging to a
      family with hereditary breast cancer were cytogenetically analyzed. Clonal
      chromosome abnormalities were detected in five of the six prophylactically
      removed breasts, all of which had the histologic diagnosis epithelial hyperplasia
      without atypia, and in the in situ carcinoma. The same karyotypic imbalance, a
      loss of 3p12-14, was detected in the in situ carcinoma as well as in one of the
      hyperplasias, indicating that these bands may harbor a pathogenetically relevant
      gene in this breast cancer family. The finding of chromosome aberrations in
      clonal proportions in the prophylactically removed breasts indicates that a
      neoplastic process was already present, lending support to the view that
      prophylactic bilateral mastectomy in these high-risk individuals prevented the
      development of breast carcinoma.

PMID- 8861837
TI  - Breast cancer survivors: psychosocial concerns and quality of life.
AB  - PURPOSE: To describe the psychosocial concerns and quality of life of breast
      cancer survivors evaluated 2 and 3 years after primary treatment. METHODS: A
      sample of 139 breast cancer survivors who had been interviewed during the first
      year after primary treatment participated in a mailed survey at 2 years (N = 69)
      and 3 years (N = 70) after initial surgery. A random sample of these survivors
      were also interviewed in person. The mailed questionnaire included standardized
      instruments to assess quality of life (QL), rehabilitation needs, and
      psychological distress. Additional survey questions were developed to examine
      post-surgical recovery, employment and insurance problems, social support, and
      existential concerns. The in-person interviews expanded on these questions and
      systematically compared these patients' rehabilitation needs to those which
      existed at the time of an interview 1 year after surgery. RESULTS: The 2 and 3
      year participants in this follow-up study did not differ from each other on their
      prior assessments with standardized QL instruments during the first year after
      surgery, nor did they differ from the full study sample of 227 women. The scores
      on the Profile of Mood States and the Functional Living Index-Cancer were the
      same for the 2 and 3 year survivor groups and did not differ from the previous
      assessments at 1 year after initial treatment. The scores on the Cancer
      Rehabilitation Evaluation System showed a significant decline in Global Quality
      of Life, Sexual Functioning and Marital Functioning between the 1 year and 3 year
      evaluations. For the 2 year sample only Sexual Functioning showed a deterioration
      between the 1 and 2 year evaluations. Using the RAND 36-Item Health Survey 1.0,
      the breast cancer survivors were compared with patients from the Medical Outcomes
      Study. The breast cancer survivors demonstrated higher levels of functioning in
      many dimensions (role functioning, social functioning, pain, and general health)
      than the patients with chronic medical conditions. In spite of relatively good
      physical and emotional functioning on this generic measure of health status and
      quality of life, these breast cancer survivors reported a number of important and
      severe rehabilitation problems that persisted beyond one year after primary
      treatment. Especially frequent were problems associated with physical and
      recreational activities, body image, sexual interest, sexual function, and
      problems with dating for those who were single. CONCLUSIONS: Breast cancer
      survivors appear to attain maximum recovery from the physical and psychological
      trauma of cancer treatment by one year after surgery. A number of aspects of QL
      and rehabilitation problems worsen after that time. Nevertheless, breast cancer
      survivors rate their QL more favorably than outpatients with other common medical
      conditions, and they identify many positive aspects from the cancer experience.

PMID- 8861838
TI  - Fluorescent in situ hybridization assessment of chromosome 8 copy number in
      breast cancer.
AB  - Conventional cytogenetics of breast and other solid tumors has been hampered by a
      number of factors. An analysis of breast tumor tissues was therefore undertaken
      using fluorescent in situ hybridization (FISH). A total of 34 specimens were
      analyzed using a chromosome 8-specific alpha-satellite probe. Various approaches
      were tested and compared. Among 30 informative samples, 11 infiltrating ductal
      carcinomas, not otherwise specified (NOS), 5 ductal carcinomas in situ, 5 lobular
      carcinomas, 3 papillary carcinomas, and 6 benign lesions were studied. Of the 11
      cases of infiltrating ductal carcinomas (NOS) analyzed, four cases showed 3
      signals, one case showed 4 signals, and the rest showed 2 signals. Of the 5 cases
      of ductal carcinoma in situ samples, 1 showed 3 signals and the other 4 cases
      showed 2 signals. All cases of lobular carcinomas, papillary carcinomas, and
      benign lesions showed 2 signals. We inferred from these data that 36% of the
      infiltrating ductal carcinomas (NOS) were trisomic and 9% were tetrasomic,
      whereas 20% of the ductal carcinomas in situ were trisomic. All samples from
      lobular carcinomas, papillary carcinomas, and the benign lesions were disomic.
      From our preliminary data, it can further be concluded that a subset of breast
      cancer is characterized by chromosome 8 trisomy. These data are consistent with
      an ever-increasing database on the association of chromosomal 8 trisomy with
      other cancers such as leukemia, lymphoma, prostate cancer, ovarian carcinoma,
      salivary gland tumor, malignant melanoma, desmoid tumors, and recently
      gestational trophoblastic disease. It is also noted that the ability to analyze
      formalin-fixed, paraffin-embedded archival material will enable a more
      comprehensive cytogenetic study of breast cancer than is currently available.

PMID- 8861839
TI  - Effects of secretory products of breast cancer cells on osteoblast-like cells.
AB  - The pathogenesis of breast cancer-induced osteolysis remains largely unknown. To
      evaluate the potential role of osteoblasts as target cells during this process,
      we incubated SaOS-2 human osteoblast-like cells (OBL) with culture media
      conditioned by proliferative (PM, 'Proliferation Media') or confluent (CfM,
      'Confluence Media') MCF-7 human breast cancer cells. CfM decreased the growth of
      OBL by 26% (P < 0.01) while PM was without significant effect on this parameter.
      In contrast, both PM and CfM obtained from MCF-7 cultures increased the cyclic
      AMP (cAMP) response of OBL to the osteolytic agents PTH (10(-8) M) and PTH
      related peptide (PTHrP, 10(-8) M) by a factor of about 3 (P < 0.001), and to
      prostaglandin E(2) (PGE(2),10(-6) M) by a factor of about 2 (P < 0.01). No
      significant modulation of OBL growth or sensitivity to PTH, PTHrP, or PGE2 was
      induced by media obtained from HBL-100 non-malignant immortalized breast
      epithelial cell cultures. 17betaestradiol (E(2), 10(-8) M) and the antiestrogen
      tamoxifen (Tam, 10(-7) M) added for 48 h to MCF-7 cultures before collecting
      conditioned media attenuated and potentiated, respectively, the PM- but not the
      CfM-induced increase in the response of OBL to PTH or PTHrP Along the same line,
      the addition to MCF-7 conditioned media of a polyclonal anti-transforming growth
      factor-beta (TGF-beta) antibody attenuated by about 25% (P < 0.01) the PM-induced
      increase in OBL response to PTH and PTHrP while abrogating the modulatory effects
      of E(2) and Tam on that response. Together, our results indicate that MCF-7
      breast cancer cells secrete factors which inhibit the growth of OBL and increase
      their sensitivity to various osteolytic agents. TGF-beta was only partly
      responsible for these effects, and accounts for their modulation by E(2) and Tam.
      The identification of other osteoblast-modulatory factor(s) should contribute to
      a better understanding and treatment of breast cancer-induced osteolysis.

PMID- 8861840
TI  - Cellular localisation by in situ hybridisation of cathepsin D, stromelysin 3, and
      urokinase plasminogen activator RNAs in breast cancer.
AB  - We have compared by RNA in situ hybridisation on serial cryo-sections the
      distribution of cathepsin D (cathD), stromelysin 3 (strom-3), and urokinase
      plasminogen activator (UPA) gene expression in different tissues of human benign
      and malignant mammary tumors. Cath-D expression was found to be higher in
      adenocarcinomas compared to non-tumoral glands. The cath-D RNA was located in
      mammary epithelial cancer cells rather than in fibroblasts, indicating that the
      cath-D gene was overexpressed in cancer cells, where the corresponding protein
      determined by immunohistochemical staining had been shown to be accumulated (E
      Roger et al., Human Pathol 25: 863-871,1994). In contrast strom-3 RNA in adjacent
      tissue sections used as a control of tissue localisation was mostly expressed in
      peritumoral fibroblasts rather than in cancer cells confirming previous results
      of Basset et al. and validating our methodology. UPA RNA was detected both in
      tumor cells and in stromal cells. In benign lesions the 3 protease RNAs were
      mostly found in epithelial cells. Stromal cells expressed UPA RNA in 5 of 7
      lesions, cath-D and strom-3 in only one sample. We conclude that in breast cancer
      patients, cath-D gene expression is increased in epithelial mammary cancer cells
      at the RNA level as well as at the protein level, suggesting an altered
      transcriptional regulation. In non malignant lesions, the distribution was
      different with a predominant distribution in epithelial mammary cells for the 3
      protease messenger RNA.

PMID- 8861842
TI  - AIDS related neoplasms in Genoa, Italy.
AB  - The study defines the epidemiological characteristics of HIV-infection in the
      population of Genoa and estimates the entity of AIDS-cancer association. The
      cohort includes 317 subjects resident in the Municipality of Genoa, aged above 14
      years and notified prior to 31 December 1991 and/or dead from AIDS in the period
      1988-1991. From 1984 to 1991, 44 cases of tumour were recorded. The comparison
      between the rate ratios found in the AIDS patients' cohort and in the general
      population of Genoa strengthen the significant association highlighted in
      literature regarding overall cancer, 26.7 (p < 0.05), and in particular, Kaposi's
      sarcoma, 3239.4 (p < 0.05); non-Hodgkin's lymphomas, 84.8 (p < 0.05); Hodgkin's
      lymphomas, 20.6 (p < 0.05). Moreover, a significant increase in the risk of
      testicular seminoma, 61.5 (p < 0.05) and lung cancer, 18.0 (p < 0.05) is
      confirmed.

PMID- 8861841
TI  - Epidermal growth factor receptor and c-erbB-2 expression in normal breast tissue
      during the menstrual cycle.
AB  - EGF receptor (EGF-R) and c-erbB-2 are homologous tyrosine kinase transmembrane
      receptors. They are involved in controlling proliferation, and probably
      differentiation, of normal breast epithelial cells, and their expression has been
      linked to the prognosis of breast cancer. Their physiological roles in normal
      breast tissue remain to be elucidated, as most studies to date have involved
      breast cancer cell lines. We studied the location of EGF-R and c-erbB-2 in 100
      samples of normal breast with standard immunohistochemical methods and double
      labelling techniques. EGF-R was mainly expressed on the stroma and myoepithelial
      cells, whereas c-erbB-2 expression was exclusively epithelial. An image analyser
      was used to quantitate variations in their expression during the menstrual cycle.
      EGF-R and c-erbB-2 expression on epithelial cells was stronger during the luteal
      phase than the follicular phase (p < 0.01 for EGF-R). The pattern of expression
      was also compared with that in 28 breast cancers and 7 fibroadenomas.

PMID- 8861843
TI  - Attitudes and opinions of French cardiologists towards smoking.
AB  - To assess attitudes and opinions of French cardiologists towards tobacco, a
      postal survey was performed in 1993 of all members of the French Society of
      Cardiology using a questionnaire designed by the World Health Organisation (WHO)
      and the International Union against tuberculosis and lung diseases (IUATLD) for
      health professionals. 730 cardiologists responded to the mailing. The mean age of
      them was 47 + or - 9 years, 84% were males. The prevalence of smoking was 27%
      (14% daily smokers and 13% occasionally smokers). There were more never smokers
      in age group < 45 than in those aged 45 and more (33% vs 21%). Of daily smokers,
      42% claimed to have made a serious attempt to stop smoking, but only 16% expected
      to have stopped within five years of the survey. French cardiologists aged 29-45
      years had a better knowledge of tobacco related respiratory and cardiovascular
      diseases than those over 45 years old. Only 64% (54% of daily smokers) would
      counsel a patient to stop smoking if he did not have a smoking related illness
      and did not himself raise the question. 53% thought they had sufficient knowledge
      to advise their patients on stopping smoking. The results compared to those of
      the French general practitioners survey, showed a lower prevalence of daily
      smokers. French cardiologists especially those aged 29-45, have a better
      knowledge of the risk of cardiovascular diseases. But only 64% of them would
      advise any smoker patients. These results also demonstrated the influence of
      personal smoking on the attitude of cardiologists towards smoker patients.

PMID- 8861844
TI  - Birth prevalence of congenital malformations in Bavaria, Germany, after the
      Chernobyl accident.
AB  - This study considers whether or not exposure to radioactive fallout from the
      Chernobyl accident led to an increased prevalence of congenital malformations in
      infants born in Bavaria, the German state with the highest levels of
      contamination after the accident. The odds ratios for major malformations after
      the accident relative to before were used as indicators for adverse health
      effects. Since measurements of caesium in soil showed that contamination was
      considerably higher in Southern Bavaria than in Northern Bavaria, the odds ratios
      were calculated for both regions separately. Analysis did not show a significant
      increase in any of the odds ratios of the selected malformations in Southern
      Bavaria as compared to Northern Bavaria. Consequently, this study provides no
      evidence that radiation from Chernobyl caused an increase in the birth prevalence
      of major congenital malformations.

PMID- 8861845
TI  - Is maternal asthma a risk factor for low birth weight? Results of an
      epidemiologic survey.
AB  - The association between history of asthma in the mother and low birth weight (<
      2,500 g) was studied in 2,929 primary schoolchildren, randomly selected from
      three areas of the Lazio Region, Italy, and enrolled in a cross-sectional survey
      to assess their health status in relation to environmental factors. A history of
      asthma in the mother was associated with a higher prevalence of low birth weight,
      with a crude OR of 2.95 (95% CI 1.10-6.72). After stratification for other
      variables, an association was still present only for males (OR 4.13; 95% CI 1.01
      12.53), when mothers had smoked in pregnancy (OR 8.02; 95% CI 1.63-32.28) and
      were resident in an industrial town (OR 10.21; 95% CI 2.69-32.27). An OR of 6.43
      was also found when mothers belonged to low social class, but the 95% CI included
      the unity. These results suggest that a history of asthma in the mother is a risk
      factor for low birth weight, but only when other adverse factors are concurrently
      present.

PMID- 8861846
TI  - A comparative study of mortality in agricultural and industrial areas in Spain.
AB  - The three main causes of contamination in the industrialized world are energy
      production, and industrial and agricultural activities. The aim of the present
      study was to examine changes in cause of death in order to contrast causes of
      death between agricultural and industrial areas. To this effect we have selected
      four zones--two predominantly industrial and two mainly agricultural--within the
      Valencian Community. Mortality figures were gathered corresponding to the same
      period 1976-1989, published by the Conselleria de Sanitat i Consum of the
      Generalitat Valenciana (Valencian Community health authorities). Thirty large
      groups of causes of death were established for posterior analysis. Mortality rate
      was defined as the number of deaths per 100,000 inhabitants, standardizing the
      data by the direct method. A simple regression analysis was performed for each
      cause of death and in each health coverage area studied, to determine the
      tendencies characterizing each area in time. A statistical significance test was
      also carried out. A statistically significant increase (95% confidence interval)
      was observed for digestive cancer, respiratory cancer, benign tumors and non
      specific neoplastic diseases in the industrial areas. In the agricultural areas,
      a significant decrease (95% confidence interval) was observed in tuberculosis and
      respiratory diseases and infections. Relative risk (RR) was calculated and thus,
      tuberculosis, mental and central nervous system disorders, respiratory infections
      and diseases, and male genital disorders were more frequent in agricultural
      areas.

PMID- 8861847
TI  - Mortality amongst Paris fire-fighters.
AB  - This paper is the first mortality cohort study undertaken in France to examine
      the association between fire-fighting and cause of death. The cohort investigated
      in this study consisted of 830 male members of the Brigade des sapeurs-pompiers
      de Paris (BSPP). These professional had served for a minimum of 5 years on 1
      January 1977. They were monitored for a 14 year period, finishing 1 January 1991.
      When compared to the average French male, the Paris fire-fighters were found to
      have a far lower overall mortality (SMR = 0.52 [0.35-0.75]). None of the cause
      specific SMRs were significantly different from unity. However a greater number
      of deaths than expected was observed for genito-urinary cancer (SMR = 3.29),
      digestive cancer (SMR = 1.14), respiratory cancer (SMR = 1.12) and
      'cerebrovascular disease' (SMR = 1.16). The low overall SMR observed was
      consistent with the healthy worker effect. As for cause specific SMRs, they will
      be confirmed or invalidated by a further analysis as the follow-up of this cohort
      is being carried on.

PMID- 8861848
TI  - Vaccine-associated cases of poliomyelitis over a 30 year period in East Germany.
AB  - A report is presented about studies on poliovirus type 3 isolates from vaccine
      associated cases or contacts of cases of paralytic poliomyelitis, observed over a
      period of 30 years in East Germany (former GDR). In the viral isolates, some
      mutations were found in comparison to the Sabin vaccine type 3 strain,
      distributed over the whole genome. The significance of these mutations has been
      discussed, especially the mutation at position 472 in the 5' noncoding region
      found in all the isolates investigated. In five isolates, intertypic
      recombination between Sabin type 3 and Sabin type 1 vaccine strain occurred.
      Primary and secondary structures were analysed for the recombination sites.

PMID- 8861850
TI  - Diarrhea caused by a Cyanobacterium-like organism.
AB  - Seven cases of watery diarrhea of explosive onset, three of them ending within
      two weeks, are discussed. The cause of diarrhea is believed to be the presence of
      an organism called Cyanobacteriumlike organism. These are non-refractile,
      spherical bodies, 8-9 micrometers in diameter, which take on a faint to deep pink
      color after modified kinyoun acid-fast staining. Risk factors such as travel to
      and from warm regions, and water as a possible source of infection are briefly
      discussed.

PMID- 8861849
TI  - Seroepidemiology of rickettsial infections in Morocco.
AB  - The prevalence of antibodies reactive with Rickettsia conorii, Rickettsia typhi,
      Coxiella burnetii and Ehrlichia chaffeensis was investigated using indirect
      immunofluorescence (IFA) test on human sera obtained from 300 blood donors in
      Casablanca and 126 sera obtained from clinical laboratories in Fez. In sera from
      Casablanca, antibodies reactive at titers > or = 1:32 were found against R.
      conorii (7%), and R. typhi (1.7%), but not against E. chaffeensis. In the sera
      from Fez, antibodies were also detected against R. conorii (5.6%), R. typhi (4%),
      but not against E. chaffeensis. By Western immunoblotting, seroprevalence for R.
      conorii was in Casablanca and 4.8% in Fez. Antibodies reactive at titers > or =
      1:50 against C. burnetii (phase II) were present in sera from Casablanca (1%) and
      Fez (18.3%).

PMID- 8861851
TI  - The use of PCR ribotyping for typing strains of Listeria spp.
AB  - The potential of PCR ribotyping for discriminating between and within various
      species of Listeria, as well as strains of Listeria monocytogenes was examined.
      In total, 49 strains of Listeria monocytogenes and 12 isolates of Listeria spp.
      were analyzed. The genomic DNA isolated from these strains was subjected to PCR
      amplification in the regions between 16S and 5S rRNA. Amplifications were
      performed with both low and high concentrations of Taq polymerase. Length
      polymorphisms in the amplified DNA products enabled distinction between various
      strains of Listeria spp. and between various serotypes of L. monocytogenes. Six
      composite profiles for serotype 4b strains, 8 for 1/2a strains and 11 for 1/2b
      strains, were observed. In addition, several different PCR ribotyping strategies
      were evaluated. Restriction fragment length polymorphisms of the spacer region
      between the 16S and 23S rRNA genes of 16 strains of L. monocytogenes were not
      observed, except for two isolates. PCR ribotyping analysis displayed promise as
      an alternative to traditional L. monocytogenes molecular typing methods.

PMID- 8861852
TI  - The Jerusalem seventy-year-old longitudinal study. I: Description of the initial
      cross-sectional survey.
AB  - The main objectives of our first cross-section of a longitudinal study of a
      cohort of 70 year olds in Jerusalem, are to survey the social and medical
      conditions of the heterogeneous elderly population and to contribute to the
      knowledge of aging processes for specific age-groups. Whereas, most previous
      surveys were conducted on homogeneous and stable population groups, the elderly
      of Jerusalem provide the basis for ethnographic comparisons and for assessing the
      impact of profound historical and personal changes. From a representative
      systematic sample (from a geographically sorted electoral register) of 759
      persons, 605 persons replied to our home-visit questionnaire gathering data on
      migration history, dwelling conditions, health status, health service
      utilization, employment status, activities of daily living, social support, use
      of drugs and war experience. Later on, 463 persons attended our geriatric
      research institute where we gathered information from in-depth anamnesis and
      physical examination, as well as cognitive and psychological tests. In addition,
      a battery of biochemical and hematological blood tests were performed as well as
      urine analysis and culture, ECG and pulmonary function tests. The heterogeneity
      of our cohort population is demonstrated by the finding that 84% were born in 40
      different countries outside of Israel. In contrast, in the seventy-year old
      population studied in Gothenburg, Sweden, only 3% were not native born. In the
      years 1996, 2001 and 2006, our initial study cohort will be re-examined and
      compared to control groups representing states of no-survey intervention until
      ages 75, 80 and 85 years old. This background paper describes the study design,
      protocols and procedures. The responders were found to be representative of the
      70 year old Jewish population in Jerusalem as a whole, in terms of mortality and
      hospital utilization rates. The results of the study to be reported in subsequent
      papers will allow conclusions regarding all 70 year old Jews in Jerusalem to be
      made.

PMID- 8861853
TI  - The Jerusalem seventy year olds longitudinal study. II: Background results from
      the initial home interview.
AB  - Basic background information is presented from a representative sample of 605
      West Jerusalem Jewish residents aged 70 years in 1990/91. A followup survey of
      the original cohort is planned for 1996, in addition to a similar sized control
      group of persons not studied in 1990/91. This paper describes the demographic
      characteristics, marital status, household composition, migration patterns,
      language comprehension, education, employment status, religious practices,
      household conditions, health status, health service utilization, health
      practices, use of medications, social contacts and activities of daily living of
      the study population. Only 16% of the study population were born in Israel, the
      remainder were born in forty different countries in four continents. This article
      also presents some ethnic comparisons within our cohort. Some significant
      differences were found between ethnic sub-groups in self-reported chronic
      diseases. However, many of these differences disappeared when socio-economic
      covariates were considered. Differences were also found when specific countries
      were considered. Compared to Polish-born Jews, Moroccan-born Jews had lower
      economic status, less education, more family contacts and less faith in
      physicians. Moroccan-born Jews also reported more morbidity for cerebrovascular
      disorders, emphysema and glaucoma.

PMID- 8861854
TI  - A seroepidemiologic survey of immunity against poliomyelitis in a group of HIV
      positive and HIV negative drug addicts.
AB  - In a seroepidemiological study performed to investigate immunity against
      poliomyelitis in a population of drug addicts in a rehabilitative residential
      centre we demonstrated a widespread lack of poliovirus neutralizing antibodies.
      This was more evident in the HIV positive subjects, 27% of whom were seronegative
      for poliovirus type 1, 27% for type 2 and 34% for type 3, with 11% seronegative
      for all three types. These results indicate a gap in immunity to poliomyelitis in
      the examined population.

PMID- 8861855
TI  - Prevalence of antibodies to rickettsiae in the north-western part of Bosnia and
      Herzegovina.
AB  - The prevalence of rickettsial antibodies in north-western part of Bosnia and
      Herzegovina was studied. Among 231 sera tested by complement fixation (CF)
      positive were: 61.5% for Rickettsia typhi, 4.3% for R. prowazekii, 1.7% for R.
      conorii and 19.0% for Coxiella burnetii. Of 183 sera tested by indirect
      immunofluorescence assay (IFA) 37.7% reacted with R. typhi, 1.6% with R. conorii
      and 22.4% with C. burnetii. The results show that at least R. typhi and C.
      burnetii are highly endemic in this area.

PMID- 8861856
TI  - Seroprevalence of toxocariasis in children and a case of VLM.
AB  - An epidemiological study on toxocariasis in children was carried out at our
      hospital (Madrid, Spain) in relation with a case of toxocariasis in a child with
      chronic hypereosinophilia. The study was based on a positive result of the ELISA
      test, using excretory-secretory antigen from Toxocara canis. The seroprevalence
      in children was 1%.

PMID- 8861857
TI  - Evaluation of a commercially available ELISA for detection of Giardia lamblia
      antigen in faeces: preliminary results in unconventional samples.
AB  - The sensitivity and specificity of a commercial ELISA for the diagnosis of G.
      lamblia were assessed on a series of 52 formalin-ether concentrated,
      unrefrigerated faecal samples after prolonged storage. Before storage the CELISA
      did not perfectly accord with microscopy. All the 30 microscopically positive
      samples scored highly positive on ELISA after storage, including 2 samples that
      had given a false negative result when examined soon after collection. There was
      no false positive ELISA. The sensitivity of the test therefore seems to be
      enhanced by storage at room temperature without any corresponding fall in
      specificity.

PMID- 8861858
TI  - Human leptospirosis in Italy, 1986-1993.
AB  - In the eight-year period 1986-1993, the Italian National Center for Leptospirosis
      and the Regional Leptospira Laboratories confirmed 312 cases of clinical
      leptospirosis by using the microscopic agglutination (MA) assay. The majority of
      cases was observed in Northern regions of the Country. Cases were reported in all
      age groups, but were most common in the working-age population. Of 312 cases, 291
      (93.3%) occurred among males. The largest number of infections was ascribed to
      occupational activities (45.8%). The typical leptospiral seasonal course, with a
      peak during the summer, was observed. Involvement of the liver was the most
      frequent manifestation. Influenza-like symptoms were the only signs of illness in
      11.1% of cases. Anti-leptospira antibodies, cross-reacting with two or more
      serovars, were found in 28.2% of sera. The most frequent serovar-specific
      antibodies were those against poi, icterohaemorrhagiae, bratislava, copenhageni
      and sejroe.

PMID- 8861859
TI  - Absence of HIV-1 and HIV-2 infection in different populations from Alexandria,
      Egypt.

PMID- 8861860
TI  - An imported cholera case infected with both O139 synonym Bengal and O1 Vibrio
      cholerae in Japan.

PMID- 8861861
TI  - Current trends in typing of bacterial strains for medical purposes.

PMID- 8861862
TI  - The potential for bacterial testing of blood products.

PMID- 8861863
TI  - Proposed new bacterial taxa and proposed changes of bacterial names published
      during 1994 and considered to be of interest to medical or veterinary
      bacteriology.

PMID- 8861864
TI  - A trojan horse mechanism in the pathogenesis of infective endocarditis: a
      hypothesis.

PMID- 8861865
TI  - Kinetics and regulation of erythrogenic toxins type A and C during growth of
      Streptococcus pyogenes.
AB  - The production of erythrogenic toxins type A (ETA) and C (ETC) is described as a
      function of growth kinetics. Group A streptococcal strains C 203 S and NY 5 were
      cultivated in yeast-peptone extract, Todd-Hewitt medium and a synthetic medium.
      Two main growth phases occurred during growth: a first logarithmic phase and a
      second linear phase. These phases were separated by a short stationary interphase
      caused by limitation of the amino acids L-serine and L-leucine. Maximum
      production of ETC was observed during the logarithmic phase, it was correlated to
      a high level of viable cells. ETA was produced mainly during the short stationary
      interphase. The production of ETC is regulated by L-isoleucine. A stagnation or
      reduction of the concentration of viable cells was observed during the
      interphase. The phosphate limitation caused during streptococcal growth induced
      expression of the extracellular protein phosphatase and surprisingly, of a serine
      proteinase activity. The association between these results and the pathogenicity
      of streptococci is discussed.

PMID- 8861866
TI  - Characterization of an isolate of the newly described species Mycobacterium
      interjectum.
AB  - The phenotypic features of a clinical isolate of the new species Mycobacterium
      interjectum, identified on the basis of its 16S rRNA gene sequence, are compared
      with those of the type strain. The differentiation of M. interjectum from
      Mycobacterium gordonae or Mycobacterium scrofulaceum is not achievable on the
      basis of phenotypic traits usually tested for mycobacterial speciation, but it
      can be reached by 16S rRNA gene sequencing or by high performance liquid
      chromatography (HPLC) of cell wall mycolic acids. The former reveals sequence
      identity with the signature region of the type species, and the latter yields a
      profile which is easily differentiated from those of the other two species. The
      unique HPLC profile of M. interjectum is reported here for the first time and so
      are the MICs of a wide spectrum of drugs.

PMID- 8861867
TI  - Comparison of intrathecal synthesis of Treponema pallidum-specific IgG antibodies
      and polymerase chain reaction for the diagnosis of neurosyphilis.
AB  - An indirect Treponema pallidum-IgG enzyme-linked immunosorbent assay (Tp-IgG
      ELISA) was used for the estimation of intrathecal synthesis of specific IgG
      antibodies in patients with syphilis. Detection of T. pallidum DNA in
      cerebrospinal fluid (CSF) samples of syphilitic patients was performed by
      amplification of treponemal DNA, using the polymerase chain reaction (PCR). Both
      methods were compared as to their suitability for diagnosis of neurosyphilis in
      37 patients with syphilis. Intrathecal synthesis of T. pallidum-specific IgG and
      PCR was negative in 16 patients with treated syphilis or untreated secondary
      syphilis. In contrast, an intrathecal IgG antibody production was found in all 21
      patients with treated or untreated neurosyphilis. PCR was only positive in CSF
      samples from six out of ten patients with untreated neurosyphilis. The findings
      suggest that the intrathecal production of T. pallidum-specific IgG antibodies is
      an important indicator for the diagnosis of neurosyphilis. In addition, a
      positive result by PCR performed in CSF establishes a diagnosis of active
      neurosyphilis.

PMID- 8861868
TI  - In vitro demonstration of the invasive ability of Campylobacters.
AB  - By means of the gentamicin HEp-2 cell invasion assay, it was demonstrated that
      82% of the Campylobacters tested were cell-invasive, including 83% of isolates
      from bloody diarrhoea and 80% of isolates from watery diarrhoea. The large number
      of invasive strains from watery diarrhoea suggests the possible role of
      invasiveness in the production of watery diarrhoea. Whether this stage can
      progress further to more severe symptoms such as bloody diarrhoea remains to be
      elucidated. Whether this progression to bloody diarrhoea occurs as a result of
      toxin production is still debatable. In Vero cells, invasion was less efficient
      and intracellular multiplication was not observed.

PMID- 8861869
TI  - Sequential development of resistance to fluoroquinolones and erythromycin in an
      isolate of Campylobacter jejuni.
AB  - A severe episode of Campylobacter jejuni gastroenteritis in a patient with HIV
      infection was treated with ciprofloxacin and, because of therapeutic failure,
      subsequently with roxithromycin. After treatment, C. jejuni was again isolated
      from feces and shown to be resistant to both drugs. We present molecular evidence
      of the sequential development of both types of resistance in the patient isolate.
      To our knowledge, this is the first case with documented evidence showing
      sequential emergence of resistance to fluoroquinolones and erythromycin in a
      strain of C. jejuni during treatment.

PMID- 8861870
TI  - Postantibiotic effect and virulence factors depression induced by ciprofloxacin
      and by aminoglycosides in a clinical isolate of Pseudomonas aeruginosa.
AB  - The postantibiotic effect (PAE) was induced in Pseudomonas aeruginosa by
      ciprofloxacin, tobramycin and netilmicin (2x or 4x MIC). A longer PAE was evoked
      by a higher concentration of antibiotics. The evaluation of Pseudomonas
      aeruginosa virulence factors after treatment with suprainhibitory concentrations
      of the antibiotics tested showed that a higher suppression of elastase activity
      was associated with a longer PAE. Elastase was suppressed more effectively than
      proteinase. The highest reduction of elastase and proteinase activity (to 24.9%
      and 76.4% of the control values) was observed after treatment with ciprofloxacin.

PMID- 8861871
TI  - Susceptibility to antimicrobial agents of Streptococcus suis capsular type 2
      strains isolated from pigs.
AB  - The minimal inhibitory concentrations (MICs) for thirty-three epidemiologicaly
      unrelated clinical isolates of Streptococcus suis capsular type 2 were determined
      in relation to ampicillin, ampicillin-sulbactam, amoxicillin, clavulanate
      amoxicillin, penicillin G, cephalexin, gentamicin, streptomycin, erythromycin,
      tylosin and doxycycline, using the microtitre broth dilution procedure described
      by the U.S. National Committee for Clinical Laboratory Standards (NCCLS).
      Gentamicin was the most active compound tested, with an MIC for 90% of the
      strains tested (MIC(90)) of 0.4 mg/L. Overall, 70% of strains were resistant to
      doxycycline (MIC(90) > or = 100.0 mg/L), followed by penicillin G (51% of
      strains) (MIC(90) + or = 100.0 mg/L). Resistance to amoxicillin and ampicillin
      was 36.4% (MIC(90) 12.5 mg/L) and 33.3% (MIC(90) 50.0 mg/L), respectively. 15.2%
      of S. suis strains were resistant to streptomycin, tylosin and cephalexin with
      MIC90 values of 25.0 mg/L, 12.5 mg/L and 25.0 mg/L, respectively. A combination
      of ampicillin and sulbactam (MIC(90) 6.3 mg/L) and a combination of amoxicillin
      and clavulanate (MIC(90) 3.1 mg/L) as well as erythromycin (1.6 mg/L) were of the
      same efficacy, with a total of 9.1% resistant S. suis strains. This high
      percentage of resistance to doxycycline and penicillin G precludes the use of
      these antibiotics as empiric therapy of swine diseases.

PMID- 8861872
TI  - Postantibiotic effect of penicillin on Streptococcus anginosus.
AB  - We studied the postantibiotic effect of penicillin G on bacterial growth of two
      strains of Streptococcus anginosus by optical density readings of the cultures
      and by counting the numbers of viable cells. Duration of the effect of the drug
      in concentrations equivalent to the MICs after exposure for 2 h was 3.4 and 3.5
      h. The production of streptococcal substances was examined during the
      postantibiotic phase. The antibiotic caused an increase in deoxyribonuclease and
      a decrease in both free and cell-bound hemolysin activities of one strain. The
      other strain displayed an increase in hyaluronidase and both free and bound
      hemolysin production.

PMID- 8861873
TI  - Phagocytosis of Helicobacter pylori bacteria differing in the heparan sulfate
      binding by human polymorphonuclear leukocytes.
AB  - Heparan sulfate binding proteins (HSBPs) of Helicobacter pylori facilitate
      bacterial phagocytosis by human polymorphonuclear leukocytes (PMNs). H. pylori 25
      strain which demonstrates a strong heparan sulfate binding activity was found to
      be attached to/ingested by PMNs in greater numbers than H. pylori strain 17874
      bacteria which lacked this activity. Moreover, heparin inhibited the uptake of
      cells of H. pylori strain 25 but not of cells of H. pylori strain 17874 by PMNs.

PMID- 8861874
TI  - Experimental melioidosis in inbred mouse strains.
AB  - Experimental infection was induced in three inbred mouse strains (BALB/c, BDF1
      hybrid and C57BL) by i. p. inoculation with Pseudomonas pseudomallei. The
      bacterial load in the viscera and the host response induced in different
      compartments (blood, peritoneal cavity and organs) were determined. Blood cell
      parameters and peritoneal exudative cell populations were evaluated during the
      infection with the aid of an automated haematology analyser Technicon H-1. It was
      found that all mouse strains produced a similar intraperitoneal inflammatory
      response with predominance of granulocytes at the early stage of infection and
      subsequent increase of macrophages especially in BDF1 hybrid and BALB/c mice. The
      highest bacterial count found in the liver and spleen of C57BL was associated
      with corresponding tissue damage (purulent pneumonia, abscesses in liver,
      karyorrhexis of hepatocytes and meningoencephalitis). The degree of bacterial
      load and histological changes found in BALB/c and BDF1 hybrid mice were lower
      than in C57BL mice. The results show that the variations in the infection
      magnitude among inbred mouse strains are host-dependent.

PMID- 8861875
TI  - Cryptococcosis associated with HIV negative Indian patients and HIV positive
      Indian blood donors.
AB  - Cryptococcosis, particularly cryptococcal meningitis (CM), has become an
      increasing problem globally in the AIDS era. In the present investigation we have
      made an effort for the first time to study Indian cases (100) both HIV-positive
      (23 cases, male, mostly Indian professional blood donors, PBDs') confirmed by an
      ELISA test and Western Blot but asymptomatic for CM and HIV-negative (77:49 male
      and 28 female) asymptomatic or symptomatic. These subjects were patients from the
      Lucknow hospitals admitted during the period between February, 1991 to February,
      1994, for suspected cryptococcosis or CM. Of those cases, 10% were positive for
      cryptococcosis or CM. Meningoencephalitis was the dominant clinical manifestation
      in four (HIV-negative) cases of CM. CT scanning of the head of those cases
      revealed a noncommunicating hydrocephalus due to aqueductal stenosis (in 2 cases)
      and a communicating hydrocephalus with granuloma (by MRI) in another case. The
      latex agglutination test (LAT) of the sera was positive for Cryptococcus antigen
      in 6 (26%) of the (HIV-positive) patients and 4 (5%), of the HIV-negative cases.
      In the cases of CM, there was a lower antigen titre in CSF than in the pronase
      treated sera. The LAT was found to be useful in diagnosis of cryptococcosis,
      especially in asymptomatic cases. The CSF of CM-positive cases revealed low
      levels of glucose, reduced cell count and high proteins. Among the HIV-negative
      cases, the onset of meningitis in 4 cases was preceded by the presence of
      encapsulated budding yeast cells in CSF India ink smear, or cryptococci in a
      direct urine smear in one case. The CSF culture of 3 cases was positive for
      mucoid Cryptococcus neoformans, showing brown colour effect (BCE) on Staib agar
      (syn. Guizotia abyssinica creatinine agar, bird seed agar). The isolated yeast
      strains were identified as C. neoformans var. neoformans by physiological tests.
      The pathogenicity test of strains revealed virulence to BALB/c mice evidenced by
      a high mortality of mice and significantly (p < 0.05) high CN burden (> 4-5 mean
      log(10) cfu), in the brain followed by other visceral organs (lung, liver,
      spleen, kidney and heart). The in-vitro susceptibility (MIC mu gmL(-1)) of
      strains.

PMID- 8861876
TI  - Factors affecting the results of a broth microdilution antifungal susceptibility
      testing in vitro.
AB  - In experiments involving 10 antifungal drugs and 46 strains of potentially
      pathogenic fungi, the factors affecting the results of in vitro susceptibility
      testing were studied. The composition of the test medium, inoculum size,
      temperature and length of incubation were the most pronounced effects influencing
      the results of testing in vitro. Minimal inhibitory concentrations (MIC) of the
      antimycotics tested were lowest in complex media (Brain Heart Infusion,
      Antibiotic Medium 3, Sabouraud broth) except for 5-fluorocytosine which was most
      effective in Yeast Nitrogen Base medium. Inoculum sizes of 10(3) to 10(4) cfu*
      mL(-1) had no marked effect on MIC but starting from a final concentration of
      10(5) cfu*mL(-1), an abrupt increase in MIC in azole derivatives and 5
      fluorocytosine was observed. There was a direct relationship between the duration
      of incubation and MIC of fungistatic antimycotics. The influence of the
      incubation temperature became generally manifest primarily in fungi with retarded
      growth at elevated temperature (>35 degrees C). In these fungal species, a
      tendency towards a decrease in MIC with increasing temperature was apparent. The
      other factors studied (medium pH, buffer, solvent) had no substantial influence
      on the antifungal activity of the drugs tested.

PMID- 8861877
TI  - Human infection caused by Salmonellae of subspecies II to VI in Germany, 1977
      1992.
AB  - Human infections by Salmonella (S.) are usually caused by S. enterica strains
      belonging to the subspecies I (subsp.). Strains of subsp. II-VI and S. bongori
      are mostly isolated from animals or environmental specimens, and they are
      therefore considered as less pathogenic for humans. Out of 90,201 S. isolates
      examined at the German National Reference Centre for Enteric Pathogens between
      1977 to 1992, 89,798 (99.55%) belonged to S. subsp. I, while 403 (0.45%) of
      strains belonged to S. subsp. II-VI and S. bongori (formerly called subsp. V).
      108 strains belonged to subsp. II, 241 isolates to subsp. IIIa and IIIb (formerly
      called Arizona), 49 to subsp. IV, 4 to S. bongori and one isolate to subsp. VI.
      215 of the 403 isolates (53.4%) were from humans, 101 (25.1%) from reptiles, 52
      (12.9%) from various warm-blooded animals, 11 (2.7%) from foodstuffs and 12
      (3.0%) from environmental specimens. The origin of 12 (3.0%) strains was unknown.
      According to the clinical diagnosis reported by the laboratories, intestinal
      disease was associated with 176 (81.9%) out of 215 strains of human origin. 11
      (5.1%) strains had been isolated from extraintestinal infections (sepsis,
      atypical pneumonia, urinary tract and wound infections), and 28 (13.0%) strains
      from stool specimens of healthy persons. A slightly higher incidence was observed
      in children of 0-5 years of age (49 cases; 22.8%). Male persons were twice as
      often affected than females. The seasonal incidence of infections was highest in
      October and in February. In 53 cases (24.6%), travel to a foreign country was
      reported.

PMID- 8861878
TI  - Phage types and ribotypes of Salmonella enteritidis in southern Italy.
AB  - Differently from other European countries, Southern Italy was affected by a
      considerable increase in human infections due to Salmonella enterica subsp.
      enterica serovar Enteritidis (S. Enteritidis) only after 1990. On the present
      investigation, two groups of S. Enteritidis strains isolated during the low
      incidence period 1980-1984 and the epidemic period 1990-1993, respectively, have
      been submitted to phage-typing and ribotyping in order to ascertain whether the
      epidemic increase was determined by the spread of a foreign bacterial clone or
      not. Among the 150 isolates relative to the aforesaid two periods, 12 different
      phage types (PTs) were observed. PT4 was the most common phage type among the
      strains isolated in 1980-1984 (61%) as well as in those of the epidemic period
      1990-1993 (72%). PT8 was the second most frequent (33%) phage type in 1980-1984.
      It was substituted by PT1 (19%) in the 1990-1993 period. Analysis of rDNA
      patterns obtained after Hinc II digestions and Escherichia coli rRNA
      hybridizations showed 8 different patterns, A to H. The great majority of the
      strains studied (140 isolates, 93%) belonged to the ribotype A, showing a similar
      frequency both in 1980-1984 (36 of 39, 92%) and in 19901993 (104 of 111, 94%).
      The predominance of PT4 and ribotype A among both preepidemic and epidemic
      strains is in agreement with the hypothesis that host genetic diversity decline
      and modern farming practices in the poultry industry have facilitated a
      widespread dissemination of preexisting endemic strains. This hypothesis urges to
      plan new strategies in preventing S. Enteritidis infections.

PMID- 8861879
TI  - Medical scholarship: how can a practicing surgeon do research?

PMID- 8861880
TI  - A brief history of pediatric otolaryngology.

PMID- 8861881
TI  - A history of rhinology in North America.
AB  - The history of rhinology is the story of the efforts of men and women who have
      tried to help patients who have nasal and sinus disorders or other conditions
      thought to be related to the nose or sinuses. Woven through this story are the
      subplots of the progress of surgical technology, the understanding of anatomy and
      physiology, and the hit-or-miss relationship between them. Through the last half
      of the nineteenth century, great strides were made in understanding nasal and
      sinus anatomy and physiology. As that century ended and as the twentieth century
      began, there was a surge of technology that allowed a marked increase in the type
      and number of surgeries performed. Unfortunately, nasal and sinus surgery holds
      the awesome potential to promote health or to severely hurt someone. The
      knowledge of nasal physiology and anatomy had been exceeded, and often those
      operations were not in the patient's best interest. Through the middle of the
      twentieth century the basic science knowledge seems to have caught up with the
      care being provided, but as the end of the century approaches, another tide of
      surgical activity seems to be upon us. Perhaps in no other area of surgery has
      this disparity between biologic knowledge and surgical activity been so well
      demonstrated. Perhaps the next 100 years will witness a better coordination of
      these activities.

PMID- 8861882
TI  - Techniques for human temporal bone removal: information for the scientific
      community.
AB  - Human temporal bones provide an irreplaceable resource for study of the pathology
      and pathophysiology of disorders of hearing, balance, taste, and facial nerve
      function. Additional specimens are needed to study disorders for which there are
      few human specimens; to increase the number of specimens for a given disorder to
      understand the natural variability and expression of the disease entity; to
      evaluate the accuracy of otologic diagnoses and the efficacy of otologic
      treatment modalities; to apply newly available scientific methods, including
      immunohistochemistry and molecular biologic or molecular genetic techniques; and
      to teach the anatomy of the human ear and modern otologic surgical techniques.
      This article provides information for the scientific community concerning
      techniques for temporal bone and auditory brain stem removal, including
      intracranial and extracranial approaches and methods to minimize postmortem
      autolysis and cosmetic defects. Close collaboration between physicians and
      funeral directors will maximize the yield and utility of these valuable specimens
      for scientific inquiry and training.

PMID- 8861883
TI  - Physician workforce in otolaryngology.

PMID- 8861884
TI  - In vitro testing for immunoglobulin E-mediated food allergies.
AB  - The role of immunoglobulin E-mediated food allergy in subjects with allergic
      disorders, especially in patients with rhinitis and sinusitis, is underestimated
      by clinicians because of the initial attribution of these disorders to immediate
      type hypersensitivity reactions. The difficulties of diagnosing food-related
      reactions have caused further delay in their recognition and incorporation into
      the daily practice of diagnosing food allergy. Two of the diagnostic methods for
      food allergy are the in vitro assay of total immunoglobulin E and the measurement
      of food-specific immunoglobulin E levels in serum with the radioallergosorbent
      test. Measurement of specific immunoglobulin E level is the most commonly used
      but also one of the most controversial techniques. We examined 123 patients with
      rhinitis who were referred to our otolaryngology/allergy clinic between January
      and April 1995. All patients received an initial radioallergosorbent test screen,
      which included milk. We determined the positive predictive value of this positive
      screen and, in particular, of a positive test for milk in the diagnosis of
      immunoglobulin E-mediated food allergies in these patients. Conclusions were
      based on comparison with the result of an additional radioallergosorbent test
      food panel consisting of eight common and two investigational food allergens.

PMID- 8861885
TI  - Tonsillectomy in children with or at risk for velopharyngeal insufficiency:
      effects on speech.
AB  - Recent case reports have challenged the notion that tonsillectomy is
      contraindicated in patients with or at risk for velopharyngeal insufficiency. The
      purpose of this study was to quantify the effects of tonsillectomy (with or
      without adenoidectomy) on perceptual speech characteristics, aerodynamic
      measures, and endoscopic descriptions of velopharyngeal function in a clinical
      population. Fifteen children 4 to 10 years of age received preoperative and
      postoperative evaluations. Perceptual speech characteristics improved or remained
      the same for most variables. There was no statistically significant difference
      between preoperative and postoperative ratings of hypernasality or frequency and
      severity of nasal emission. However, ratings of voice quality (pitch and
      breathiness) were significantly improved after surgery. Aerodynamic measures
      showed improvement or no change in velopharyngeal function for 12 of 15 children.
      Endoscopic assessment showed improvement or no change in velopharyngeal closure
      for 7 of 11 children tested. Cross-method analysis indicated that no single
      subject showed deterioration in velopharyngeal function in all three measures.
      The data from this investigation do not support the assumption that tonsillectomy
      is contraindicated for all children with or at risk for velopharyngeal
      insufficiency.

PMID- 8861886
TI  - Hearing loss as a complication of stapes surgery.
AB  - During a 10-year period (1984-1994) 1229 stapes operations for otosclerosis were
      performed at our respective institutions by experienced surgeons well trained in
      the various techniques. Procedures included 691 stapedectomies, 234 small
      fenestrae stapedotomies, and 304 revision operations. These primary and revision
      cases resulted in 20 ears with severe sensorineural hearing loss or anacusis
      noted during the immediate postoperative period. This article will critically
      evaluate those procedures that resulted in profound hearing loss and attempt to
      determine possible reasons for this occurrence. It is hoped that these data will
      allow surgeons to identify before and/or during surgery patients at risk for
      development of this complication and therefore decrease the overall morbidity
      rate of this exacting procedure.

PMID- 8861887
TI  - Vocal fold vibration viewed from the tracheal side in living human beings.
AB  - The mucosal upheaval where the mucosal wave starts and propagates upward appears
      on the lower surface of the canine vocal fold during vibration. We investigated
      the vibratory behavior of the in vivo human vocal fold viewed from the tracheal
      side. Subjects consisted of 14 men and 6 women who had undergone tracheostomy for
      various head and neck diseases; their ages ranged from 22 to 70 years, with a
      mean of 53.9 years. The inferior aspect of the vocal fold during phonation was
      observed with the aid of a rigid oblique-view endoscope inserted through a
      tracheostoma (inferior glottoscopy). Each subject was asked to sustain the vowel
      /a/ at a comfortable pitch and loudness (easy phonation) and then at a higher
      pitch. Inferior glottoscopy could be performed during easy phonation in 19
      subjects and during high-pitched phonation in 10 subjects. During easy phonation,
      the mucosal upheaval appeared on the lower surface of the vocal fold between the
      anterior commissure and the vocal process in all 19 subjects. During high-pitched
      phonation, the vocal fold became longer, and the subglottic vault surrounded by
      the bilateral mucosal upheavals became narrower compared with those during easy
      phonation. Use of a dilated blood vessel as a landmark in one subject showed the
      location of the mucosal upheaval on the vocal fold mucosa to actually shift
      medially toward the oral side during high-pitched phonation. Despite structural
      differences between the human and canine vocal folds, the infraglottic aspect of
      the vocal fold vibration observed in the living human larynx was quite similar to
      that observed in the excised canine larynx.

PMID- 8861888
TI  - A guide to otolaryngology resources on the Internet.
AB  - The number of valuable resources for otolaryngologist-head and neck surgeons on
      the Internet continues to grow at a rapid pace. This article is a comprehensive
      guide to resources currently available.

PMID- 8861889
TI  - Inhibition of proteases in Pseudomonas otitis media in chinchillas.
AB  - The treatment of chronic suppurative otitis media caused by Pseudomonas
      aeruginosa remains a challenging problem. The virulence of Pseudomonas is related
      to its secretion of two matrix metalloproteinases, alkaline protease and
      elastase. This experiment examines the effects of a synthetic inhibitor of matrix
      metalloproteinases GM 6001, or N-(2(R)-2(hydroxyamido carbonylmethyl)-4
      methylpentanoyl)-L-tryptophane methylamide), in a chinchilla Pseudomonas otitis
      media model. Thirty chinchillas underwent bilateral subtotal tympanic membrane
      perforations. Twenty-four chinchillas underwent bilateral middle ear inoculation
      with P. aeruginosa. Chinchillas were divided into four groups of six animals
      after the establishment of otitis media. Animals in one group were controls; the
      other three groups received either gentamicin, GM 6001, or gentamicin plus GM
      6001 into the external auditory canal three times daily for 4 weeks. Clearance of
      Pseudomonas infection occurred in three ears of three animals, all in gentamicin
      groups, with or without GM 6001. Otorrhea (p = 0.0014) and external canal
      erythema (p = 0.025) were mild in the two gentamicin groups and moderate in the
      GM 6001 group when compared with bacterial controls. Animals in the GM 6001 group
      had the highest survival rate, less severe facial paralysis, and less vestibular
      toxicity than the gentamicin, gentamicin plus GM 6001, or control groups,
      although these differences were not statistically significant. This pilot study
      showed encouraging results for a role of ototopical protease inhibitors in the
      treatment of Pseudomonas otitis media.

PMID- 8861890
TI  - Voice and healing after vocal fold epithelium removal by CO2 laser vs.
      microlaryngeal stripping.
AB  - Controversy exists regarding voice recovery after the use of laser vs.
      microforceps techniques in the removal of benign vocal fold lesions. The purpose
      of this study is to compare recovery of voice and healing between groups of cats
      undergoing vocal fold epithelium removal by CO2 laser and those having vocal fold
      stripping. Fourteen adult female cats underwent standardized unilateral vocal
      fold injuries by CO2 laser ablation or stripping. After a 6-week recovery period,
      phonations were evoked by electrical stimulation of the midbrain periaqueductal
      gray area. Phonations were recorded for acoustic analysis. The larynges were
      harvested, fixed, and sectioned for histologic correlation. Acoustic analysis
      showed the mean signal-to-noise ratios in the laser group (19.72) to be
      significantly higher than those in the stripped group (13.51) (p = 0.04). The
      stripped group showed significantly greater amplitude perturbation (8.68% vs.
      2.43%, p = 0.02). No between-group difference was found for period perturbation.
      Histologically, the laser group showed minimal Reinke's space scarring and near
      normal epithelial regeneration, and the stripped group showed marked
      subepithelial scarring, often involving the vocalis muscle. These results
      demonstrate superior recovery of voice and healing in animals undergoing vocal
      fold epithelium removal with the CO2 laser. Inferior outcomes seen in the
      stripped group may be related to difficulty in preserving Reinke's space during
      epithelium removal.

PMID- 8861891
TI  - Survival of normothermic microvascular flaps after prolonged secondary ischemia:
      effects of hyperbaric oxygen.
AB  - Although hyperbaric oxygen has been shown to improve the survival rate of
      ischemic grafts and flaps of many types, it has not been studied extensively in
      free tissue transfer. This study was designed to evaluate the effect of
      hyperbaric oxygen on flap survival when exposed to critical combinations of
      primary ischemia, reperfusion, and secondary ischemia times. Unilateral abdominal
      adipocutaneous island flaps based on the superficial inferior epigastric vessels
      were raised in 133 Sprague-Dawley rats. Primary normothermic ischemia was induced
      by applying a microvascular clamp to the vascular pedicle for 6 hours. The clamp
      was removed for 2 hours of reperfusion and then reapplied for a 6-, 10-, or 14
      hour period of secondary ischemia. After completion of the secondary ischemia
      time, the clamp was removed, and the animals were randomly assigned to one of
      three treatment regimens. The control animals breathed normobaric air, and the
      others breathed normobaric 100% oxygen or hyperbaric oxygen (100% oxygen at the
      equivalent of 33 feet of seawater, 2.0 atmospheres absolute), respectively, for
      two periods of 90 minutes for 7 days. Flap survival was assessed at postoperative
      day 7 and was found to be an all-or-none phenomenon. Maximum likelihood-derived
      survival curves were fitted to the data and used to calculate the secondary
      ischemic time at which 50% of the flaps survived (D50). The D50 for the air and
      100% oxygen groups was 6 hours, whereas that for the hyperbaric oxygen group was
      10 hours. This difference in D50 was found to be statistically significant
      (analysis of variance, p < 0.05). Chi-squared statistical evaluation of pooled
      data reaffirmed a statistically significant increase in flap survival of the
      animals treated with hyperbaric oxygen vs. those treated with air or 100% oxygen
      (p < 0.03 and p < 0.01, respectively). Hyperbaric oxygen enhances the tolerance
      of normothermic, microvascular flaps to prolonged secondary ischemia. A similar
      effect was not noted in the 100% oxygen group; therefore the additional expense
      and technology of a hyperbaric chamber system is necessary to achieve this
      effect.

PMID- 8861892
TI  - Chondrocyte volume fraction distribution in porcine septal cartilage: an initial
      stereoscopic evaluation.
AB  - This study uses stereology to determine the volume fraction distribution of
      chondrocytes throughout septal cartilage. En bloc submucous resection of septal
      cartilage from four different age groups was performed. Each age group contained
      three pigs. The weight, volume, and dimensions of the septi were determined. The
      septi were fixed, embedded in plastic, sectioned vertically at regular intervals
      along their anterior-posterior axis, and stained with toluidine blue. Each
      section was further stratified horizontally to allow chondrocyte volume fraction
      changes to be observed as a function of the two-dimensional location within the
      septum. The volume fraction of the chondrocytes within the septal cartilage was
      obtained through light microscopy and stereologic technique. Nested analysis of
      variance for age groups, individuals within age groups, and locations on the
      septum was performed. Additionally, unequal number-comparison tests for age
      groups were calculated. Gross septal parameter changes regarding weight, volume,
      and length all increased with advancing age. Overall, chondrocyte volume fraction
      decreased with advancing age. Chondrocyte volume fraction was not found to vary
      along the anterior-posterior axis or along the vertical axis. Stereologic
      methodology is an unbiased, simple, and efficient technique to understand the
      distribution of cells within a tissue.

PMID- 8861893
TI  - Otalgia caused by tympanostomy tube wire.

PMID- 8861894
TI  - Intubation granuloma of the larynx.

PMID- 8861895
TI  - Ancient Egyptian reference to otology.

PMID- 8861896
TI  - Outpatient uvuloplasty.

PMID- 8861897
TI  - Emerging understanding of translation termination.

PMID- 8861898
TI  - Fifty ways to love your lever: myosin motors.

PMID- 8861899
TI  - Lessons from hereditary colorectal cancer.

PMID- 8861900
TI  - Human ICE/CED-3 protease nomenclature.

PMID- 8861901
TI  - Nomenclature: vertebrate mediators of TGFbeta family signals.

PMID- 8861902
TI  - Deleted in Colorectal Cancer (DCC) encodes a netrin receptor.
AB  - The guidance of developing axons in the nervous system is mediated partly by
      diffusible chemoattractants secreted by axonal target cells. Netrins are
      chemoattractants for commissural axons in the vertebrate spinal cord, but the
      mechanisms through which they produce their effects are unknown. We show that
      Deleted in Colorectal Cancer (DCC), a transmembrane protein of the immunoglobulin
      superfamily, is expressed on spinal commissural axons and possesses netrin-1
      binding activity. Moreover, an antibody to DCC selectively blocks the netrin-1
      dependent outgrowth of commissural axons in vitro. These results indicate that
      DCC is a receptor or a component of a receptor that mediates the effects of
      netrin-1 on commissural axons, and they complement genetic evidence for
      interactions between DCC and netrin homologs in C. elegans and Drosophila.

PMID- 8861903
TI  - UNC-40, a C. elegans homolog of DCC (Deleted in Colorectal Cancer), is required
      in motile cells responding to UNC-6 netrin cues.
AB  - UNC-6 netrin, a laminin-related protein secreted from neuroglia and neurons along
      the ventral midline, orients migrating cells and pioneering growth cones on the
      nematode epidermis. UNC-5, a cell surface protein expressed on motile cells and
      pioneer axons, orients movements away from UNC-6 sources. UNC-40, a homolog of
      the cell surface proteins DCC (Deleted in Colorectal Cancer) and neogenin, is
      also expressed on motile cells and pioneer neurons. UNC-40 acts cell autonomously
      to orient movement toward UNC-6 sources. For cells coexpressing UNC-5, it helps
      orient movement away from UNC-6 sources. Finally, UNC-40 helps determine the
      dorsoventral position of cells undergoing purely longitudinal migrations.
      Together with the recent report that DCC is a netrin receptor in vertebrates, our
      results suggest that UNC-40 is a component of UNC-6 receptors on motile cells.

PMID- 8861904
TI  - frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is
      required for CNS and motor axon guidance.
AB  - We have identified a Drosophila member of the deleted in colorectal cancer (DCC)
      gene family. The frazzled gene encodes transmembrane proteins that contain four
      immunoglobulin C2 type domains, six fibronectin type III repeats, and a
      cytoplasmic domain of 278 amino acids. Like vertebrate members of the DCC family,
      Frazzled is expressed on axons in the embryonic central nervous system and on
      motor axons in the periphery. Frazzled is also expressed on epidermis and gut
      epithelium. Null mutants in frazzled are defective in axon guidance in the
      central nervous system and in motor axon guidance and targeting in the periphery.
      The phenotypes strongly resemble those of a deletion of the two Drosophila Netrin
      genes. We have rescued the frazzled CNS and motor axon defects by expressing
      Frazzled specifically in neurons; expression in target tissues does not rescue
      the phenotype. These data, together with vertebrate studies showing binding of
      DCC to netrin, suggest that Frazzled may function in vivo as a receptor or
      component of a receptor mediating Netrin-dependent axon guidance.

PMID- 8861905
TI  - MEX-3 is a KH domain protein that regulates blastomere identity in early C.
      elegans embryos.
AB  - After the first division of the C. elegans embryo, the posterior blastomere can
      produce numerous muscles while the anterior blastomere cannot. We show here that
      maternal-effect lethal mutations in the gene mex-3 cause descendants of the
      anterior blastomere to produce muscles by a pattern of development similar to
      that of a descendant of the wild-type posterior blastomere. mex-3 encodes a
      probable RNA-binding protein that is distributed unequally in early embryos and
      that is a component of germline-specific granules called P granules. We propose
      that MEX-3 contributes to anterior-posterior asymmetry by regulating one or more
      mRNAs involved in specifying the fate of the posterior blastomere.

PMID- 8861906
TI  - Spatial and temporal controls target pal-1 blastomere-specification activity to a
      single blastomere lineage in C. elegans embryos.
AB  - The early asymmetric cleavages of Caenorhabditis elegans embryos produce
      blastomeres with distinct developmental potentials. Here, we show that the caudal
      like homeodomain protein PAL-1 is required to specify the somatic identity of one
      posterior blastomere in the 4 cell embryo. We find that pal-1 activity is
      sequentially restricted to this blastomere. First, at the 4 cell stage, it is
      translated only in the two posterior blastomeres. Then, its function is
      restricted to one of these blastomeres. This second targeting step is dependent
      on the activities of the posteriorly localized SKN-1 and asymmetrically
      segregated PIE-1 proteins. We propose that the segregation of PIE-1, combined
      with the temporal decay of SKN-1, targets pal-1 activity to this posterior
      lineage, thus coupling the regulation of this conserved posterior patterning gene
      to asymmetric cell cleavages.

PMID- 8861907
TI  - Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of
      microfilament dynamics.
AB  - Drosophila Enabled is required for proper formation of axonal structures and is
      genetically implicated in signaling pathways mediated by Drosophila AbI. We have
      identified two murine proteins, Mena and Evl, that are highly related to Enabled
      as well as VASP (Vasodilator-Stimulated Phosphoprotein). A conserved domain
      targets Mena to localized proteins containing a specific proline-rich motif. The
      association of Mena with the surface of the intracellular pathogen Listeria
      monocytogenes and the G-actin binding protein profilin suggests that this
      molecule may participate in bacterial movement by facilitating actin
      polymerization. Expression of neural-enriched isoforms of Mena in fibroblasts
      induces the formation of abnormal F-actin-rich outgrowths, supporting a role for
      this protein in microfilament assembly and cell motility.

PMID- 8861908
TI  - The chaperonin ATPase cycle: mechanism of allosteric switching and movements of
      substrate-binding domains in GroEL.
AB  - Chaperonin-assisted protein folding proceeds through cycles of ATP binding and
      hydrolysis by the large chaperonin GroEL, which undergoes major allosteric
      rearrangements. Interaction between the two back-to-back seven-membered rings of
      GroEL plays an important role in regulating binding and release of folding
      substrates and of the small chaperonin GroES. Using cryo-electron microscopy, we
      have obtained three-dimensional reconstructions to 30 A resolution for GroEL and
      GroEL-GroES complexes in the presence of ADP, ATP, and the nonhydrolyzable ATP
      analog, AMP-PNP. Nucleotide binding to the equatorial domains of GroEL causes
      large rotations of the apical domains, containing the GroES and substrate protein
      binding sites. We propose a mechanism for allosteric switching and describe
      conformational changes that may be involved in critical steps of folding for
      substrates encapsulated by GroES.

PMID- 8861909
TI  - RAG1 mediates signal sequence recognition and recruitment of RAG2 in V(D)J
      recombination.
AB  - Recent studies have demonstrated that DNA cleavage during V(D)J recombination is
      mediated by the RAG1 and RAG2 proteins. These proteins must therefore bind to the
      recombination signals, but the specific binding interaction has been difficult to
      study in vitro. Here, we use an in vivo one-hybrid DNA binding assay to
      demonstrate that RAG1, in the absence of RAG2, can mediate signal recognition via
      the nonamer, with the heptamer acting to enhance its binding. A region of RAG1
      with sequence similarity to bacterial invertases is essential for DNA binding.
      Localization of RAG2 to the signal is dependent upon the presence of RAG1 and is
      substantially more efficient with a 12 bp spacer signal than with a 23 bp spacer
      signal.

PMID- 8861910
TI  - The homeodomain region of Rag-1 reveals the parallel mechanisms of bacterial and
      V(D)J recombination.
AB  - The V(D)J recombinase subunits Rag-1 and Rag-2 mediate assembly of antigen
      receptor gene segments. We studied the mechanisms of DNA recognition by Rag-1/Rag
      2 using surface plasmon resonance. The critical step for signal recognition is
      binding of Rag-1 to the nonamer. This is achieved by a region of Rag-1 homologous
      to the DNA-binding domain of the Hin family of bacterial invertases and to
      homeodomain proteins. Strikingly, the Hin homeodomain can functionally substitute
      for the Rag-1 homologous region. Rag-1 also interacts with the heptamer but with
      low affinity. Rag-2 shows no direct binding to DNA. Once the Rag-1/Rag-2 complex
      is engaged on the DNA, subsequent cleavage is directed by the heptamer sequence.
      This order of events remarkably parallels mechanisms that mediate transposition
      in bacteria and nematodes.

PMID- 8861911
TI  - A 700 bp cis-acting region controls mating-type dependent recombination along the
      entire left arm of yeast chromosome III.
AB  - Homothallic switching of the mating-type MATa gene in Saccharomyces cerevisiae
      results from replacement by gene conversion of MAT-Ya DNA with Y(alpha) sequences
      copied from one of two unexpressed donors. MATa preferentially recombines with
      HML(alpha), located near the left end of chromosome III, but can use HMR(alpha),
      near the right chromosome end. MATa donor preference depends on a 700 bp
      orientation-independent cis-acting recombination enhancer, located 17 kb proximal
      to HML. Deletion of this element markedly reduces MATa's use of a donor inserted
      at any of four different locations along the leftmost 92 kb of chromosome III.
      This enhancer is sufficient for donor activation, since it stimulates use of the
      "wrong" donor, when it is inserted 7 kb proximal to HMR.

PMID- 8861912
TI  - Interaction between the origin recognition complex and the replication licensing
      system in Xenopus.
AB  - The origin recognition complex (ORC) binds to origins of replication in budding
      yeast. We have cloned a Xenopus homolog of the largest ORC polypeptide (XORC1).
      Immunodepletion of XOrc1 from Xenopus egg extracts blocks the initiation of DNA
      replication. We have purified Xenopus ORC, consisting of a protein complex
      similar to yeast ORC. In Xenopus egg extracts, ORC associates with chromatin
      throughout G1 and S phases. RLF-M, a component of the replication licensing
      system, also associates with chromatin early in the cell cycle but dissociates
      during S phase. We show that the assembly of RLF-M onto chromatin is dependent on
      the presence of chromatin-bound ORC, leading to sequential assembly of initiation
      proteins onto replication origins during the cell cycle.

PMID- 8861913
TI  - Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA.
AB  - The crystal structure of the human DNA polymerase delta processivity factor PCNA
      (proliferating cell nuclear antigen) complexed with a 22 residue peptide derived
      from the C-terminus of the cell-cycle checkpoint protein p21(WAF1/CIP1) has been
      determined at 2.6 angstrom resolution. p21 binds to PCNA in a 1:1 stoichiometry
      with an extensive array of interactions that include the formation of a beta
      sheet with the interdomain connector loop of PCNA. An intact trimeric ring is
      maintained in the structure of the p21-PCNA complex, with a central hole
      available for DNA interaction. The ability of p21 to inhibit the action of PCNA
      is therefore likely to be due to its masking of elements on PCNA that are
      required for the binding of other components of the polymerase assembly.

PMID- 8861914
TI  - Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a
      targeted mutation of the ICSBP gene.
AB  - Interferon consensus sequence binding protein (ICSBP) is a transcription factor
      of the interferon (IFN) regulatory factor (IRF) family. Mice with a null mutation
      of ICSBP exhibit two prominent phenotypes related to previously described
      activities of the IRF family. The first is enhanced susceptibility to virus
      infections associated with impaired production of IFN(gamma). The second is
      deregulated hematopoiesis in both ICSBP-/- and ICSBP+/- mice that manifests as a
      syndrome similar to human chronic myelogenous leukemia. The chronic period of the
      disease progresses to a fatal blast crisis characterized by a clonal expansion of
      undifferentiated cells. Normal mice injected with cells from mice in blast crisis
      developed acute leukemia within 6 weeks of transfer. These results suggest a
      novel role for ICSBP in regulating the proliferation and differentiation of
      hematopoietic progenitor cells.

PMID- 8861915
TI  - Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)
      ligands modulated by the B cell antigen receptor.
AB  - Signals from CD4+ T cells induce two opposite fates in B cells: clonal
      proliferation of B cells that bind specifically to foreign antigens and clonal
      deletion of equivalent B cells that bind self-antigens. This B cell fate decision
      is determined by the concerted action of two surface proteins on activated T
      cells, CD40-and Fas-ligands (CD40L and FasL), whose effects are switched by
      signals from the B cell antigen receptor (BCR). Foreign antigens that stimulate
      the BCR acutely cause CD40L and FasL to promote clonal proliferation. CD40L and
      FasL trigger deletion, however, when the BCRs become desensitized by chronic
      stimulation with self-antigens or when BCRs have not bound an antigen. The need
      for both Fas and CD40L to correctly regulate self-reactive B cell fate may
      explain the severe autoantibody disorders in Fas- or CD40L-deficient children.

PMID- 8861916
TI  - The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like
      fold and a structural zinc binding site.
AB  - During replication of hepatitis C virus (HCV), the final steps of polyprotein
      processing are performed by a viral proteinase located in the N-terminal one
      third of nonstructural protein 3. The structure of NS3 proteinase from HCV BK
      strain was determined by X-ray crystallography at 2.4 angstrom resolution. NS3P
      folds as a trypsin-like proteinase with two beta barrels and a catalytic triad of
      His-57, Asp-81, Ser-139. The structure has a substrate-binding site consistent
      with the cleavage specificity of the enzyme. Novel features include a structural
      zinc-binding site and a long N-terminus that interacts with neighboring molecules
      by binding to a hydrophobic surface patch.

PMID- 8861917
TI  - Crystal structure of the hepatitis C virus NS3 protease domain complexed with a
      synthetic NS4A cofactor peptide.
AB  - An estimated 1% of the global human population is infected by hepatitis C viruses
      (HCVs), and there are no broadly effective treatments for the debilitating
      progression of chronic hepatitis C. A serine protease located within the HCV NS3
      protein processes the viral polyprotein at four specific sites and is considered
      essential for replication. Thus, it emerges as an attractive target for drug
      design. We report here the 2.5 angstrom resolution X-ray crystal structure of the
      NS3 protease domain complexed with a synthetic NS4A activator peptide. The
      protease has a chymotrypsin-like fold and features a tetrahedrally coordinated
      metal ion distal to the active site. The NS4A peptide intercalates within a beta
      sheet of the enzyme core.

PMID- 8861918
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Proceedings of
      a workshop. Bethesda, Maryland, September 28-29, 1995.

PMID- 8861919
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Keynote
      address.

PMID- 8861920
TI  - Overview of perinatal HIV infection.
AB  - The global HIV epidemic is having a profound impact on the health and survival of
      children. As of 1994, it is estimated that about 2 million children worldwide
      (WHO, 1994) and 12 thousand children in the United States are HIV infected (Davis
      et al. 1995). Almost all HIV infection among infants and young children are from
      mother-to-infant transmission. By the year 2000, HIV is projected to infect 40
      million men, women, and children unless effective prevention strategies are
      developed. Perinatal HIV transmission rates currently vary from 14-40% with the
      lowest rates being seen in Europe and highest rates in Africa. Known risk factors
      for perinatal transmission include advanced maternal HIV disease, lower CD4+
      counts, and increased viral burden during pregnancy. Observational cohort data
      suggest that prenatal vitamin A levels, maternal drug use, and duration of
      membrane rupture during labor also are related to risk of transmission. The
      United States clinical trial utilizing an antiretroviral (zidovudine [AZT])
      prenatally, intrapartum, and for 6 weeks to the infant demonstrated that
      perinatal HIV transmission was reduced by two-thirds. This dramatic result gives
      strong encouragement that simpler perinatal prevention strategies applicable to
      developing countries may also be successful. A number of international studies
      are underway or planned including perinatal vitamin A and micronutrient trials in
      Africa.

PMID- 8861921
TI  - The pathogenesis of HIV disease.
AB  - HIV disease is caused by human adapted Lentiviruses, a family of mammalian
      retroviruses that use the immune systems of their hosts to persist and, as their
      name implies (lenti = slow), to produce a disease state over long periods of
      time. The pathogenesis of HIV infections is now known in enough detail to make
      decisions about intervening in the course of the disease.

PMID- 8861922
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Nutrition and
      immune function: overview.
AB  - Malnutrition can have adverse, even devastating effects on the antigen-specific
      arms of the immune system and on generalized host defensive mechanisms.
      Protein/energy malnutrition and/or deficiencies of single nutrients that assist
      in nucleic acid metabolism generally lead to atrophy of lymphoid tissues and
      dysfunctions of cell-mediated immunity. Deficiencies of single nutrients can
      impair production of key proteins. Trace element deficiencies are often
      multifactorial. Essential fatty acid deficiencies can reduce or perturb the
      synthesis of cytokine-induced eicosanoids. Arginine deficiency can diminish the
      production of nitric oxide, and deficiencies of antioxidant nutrients can allow
      increases in the damaging effects of free oxygen radicals. Humoral immunity
      continues to be maintained, although new primary responses to T-cell-dependent
      antigens are generally subnormal in both magnitude and quality. Immunological
      dysfunctions associated with malnutrition have been termed Nutritionally Acquired
      Immune Deficiency Syndromes (NAIDS). Infants and small children are at great risk
      because they possess only immature, inexperienced immune systems and very small
      protein reserves. The combination of NAIDS and common childhood infections is the
      leading cause of human mortality. NAIDS can generally be corrected by appropriate
      nutritional rehabilitation, but from a viewpoint highly important to this
      Workshop, AIDS and NAIDS are intensely synergistic. AIDS-induced malnutrition can
      lead to the secondary development of NAIDS, with its much broader array of
      additional immunological dysfunctions. The complex and far reaching insults to
      the immune system caused by NAIDS, and the synergistic combination of NAIDS and
      AIDS, thereby hasten the demise of many victims of AIDS. Aggressive nutritional
      support for children with HIV infections could delay, or lessen, the development
      of NAIDS and avoidance of NAIDS would improve both quality and length of life.

PMID- 8861923
TI  - Historical perspectives on the evolution in understanding the importance of
      nutritional care in pediatric HIV infection.
AB  - Women, perinatally-infected infants, and sexually exposed and exploited youths
      and adolescents have become a major focus of the worldwide HIV/AIDS pandemic.
      Increased perinatal screening, improvement in early infant diagnosis, and the
      benefits of primary HIV therapies have increased the numbers identified and
      longevity of infants and children living with HIV. This increase in survival is
      associated with HIV/AIDS becoming a chronic multiorgan system disease that
      requires a multidiscipline comprehensive care approach. The combination of poor
      oral intake, increased loss, and increased metabolic needs of long-term surviving
      HIV-infected children are obstacles to both survival and quality of life. HIV
      infected children and their families need supportive care services including
      nutritional as well as primary therapy. Clinical guidelines for effective
      nutrition interventions must be developed to prevent and treat failure to thrive
      and wasting syndrome. Gains in survival duration must be linked to enhanced
      quality of life through supportive care, including comprehensive nutritional
      services that have their efficacy documented by appropriate clinical trials.

PMID- 8861924
TI  - Gastrointestinal tract function and malnutrition in HIV-infected children.
AB  - Poor growth and/or weight gain was identified in the initial reports of children
      with AIDS (Oleske et al. 1983, Rubinstein et al. 1983). However, in the past 12
      years little progress has been made to understand the mechanisms for these
      observations. Data from the NIAID/NICHD multicenter Women and Infants
      Transmission Study (WITS) demonstrated that a decline in weight occurred in the
      first four months of life followed by decreased linear growth (Rich et al. 1993).
      In older children weight and height seem to decline in parallel (McKinney et al.
      1993), but loss of lean body mass may occur prior to a decline in weight (Miller
      et al. 1993). Adequate caloric intake can improve weight gain, but has little
      effect on height velocity and lean body mass (Henderson et al. 1994, Miller et
      al. 1992). Long-term survivors with HIV infection are shorter than anticipated,
      and these changes cannot be explained solely by inadequate nutrition or by
      endocrine abnormalities. The immune system, gastrointestinal tract function,
      malnutrition, and chronic or recurrent infection interact and contribute to the
      nutritional deficiencies and problems with growth observed in the HIV-infected
      child.

PMID- 8861925
TI  - Malnutrition: metabolic changes in children, comparisons with adults.
AB  - Nutritional problems of human immunodeficiency virus (HIV)-infected children are
      common, pervasive, and often frustrating to treat. Because of the strong link
      between immunity and nutrition, that will be outlined here, clinicians caring for
      HIV-infected children need to attend to nutritional deficits by trying to help
      children achieve normal growth. Scientific studies are emerging on the importance
      of nutrition in both predicting and improving clinical outcomes, such as
      hospitalization rates and survival. Current background information on pediatric
      HIV infection and the associations between nutrition and HIV will be provided in
      this presentation. As well, the growth patterns of HIV-infected children,
      pathogenesis of nutritional disorders, and current diagnostic and therapeutic
      interventions will be presented. It is hoped that this presentation will provide
      both practical advice to clinicians caring for HIV-infected children, as well as
      serving as a basis to stimulate much needed scientific research in this area.

PMID- 8861926
TI  - Newborn factors in maternal-infant transmission of pediatric HIV infection.
AB  - Factors affecting maternal-infant transmission (MIT) can be conveniently divided
      into 5 categories: (1) maternal factors (e.g. maternal immunologic status, anti
      retroviral treatment), (2) virologic factors (e.g. viral load, strain, tissue
      tropism and resistance), (3) obstetric factors (e.g. traumatic delivery,
      chorioamnionitis, C-section), (4) fetal factors (e.g. prematurity, coinfection,
      twinning) and (5) infant factors (e.g. immune status, drugs, nutrition). Several
      of these factors (e.g., prematurity, maternal medication) can be classified as
      both maternal and fetal, and some factors (e.g. nutrition) include both fetal and
      neonatal period. This review focuses on the following six fetal/ infant factors:
      (1) timing of transmission, (2) prematurity, (3) fetal and neonatal nutrition,
      (4) neonatal GI function, (5) breastfeeding, and (6) the maturity of infant's
      immune system. Ways in which these factors may influence both the rate of MIT and
      the progression of the disease in the infant are discussed.

PMID- 8861927
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Nutrition and
      immune function II: maternal factors influencing transmission.
AB  - The risk of mother-to-child transmission of HIV ranges from 15-35 percent
      depending on the population under study (Fowler and Rogers 1996, Peckham and Gibb
      1995). The recent finding that zidovudine treatment during pregnancy can reduce
      the risk of mother-to-child transmission of HIV by as much as two-thirds in some
      populations (CDC 1994, Connor et al. 1994), raises the question of which
      maternal, fetal, viral, immunologic, and placental factors play the greatest role
      in vertical transmission. It is clear that not only does the transmission rate
      vary dramatically by geographical distribution, but both the prevalence of
      infection and susceptibility of the uninfected may be higher in parts of the
      developing world. The transmission rate is significantly higher in the developing
      world presumably due to numerous factors including coinfection with other STD's,
      very little economic support for prevention, education, health maintenance or
      improving nutritional contributions to curb the spread of HIV. Furthermore, the
      strategies to reduce vertical transmission in industrialized countries are often
      not feasible in the developing world. Providing widescale availability of
      antivirals may not be feasible in areas where, to date, vitamin deficiencies
      often still exist. The healthcare budget in many of these developing countries
      cannot even pay for basic medical or prenatal services. The future directions in
      reducing the rate of mother-to-infant transmission must focus on strategies
      applicable to the developing world as well as industrialized countries. The vast
      majority of HIV in the pediatric age group is the result of vertical transmission
      of the virus. A number of maternal immunologic factors have been associated with
      vertical transmission. This paper offers a brief review of the extant knowledge
      with regard to the role of maternal factors in vertical transmission of HIV
      infection.

PMID- 8861928
TI  - Dysregulation of growth and development in HIV-infected children.
AB  - Growth dysregulation is quite common in HIV-infected children and growth failure
      is one of the most sensitive indicators of disease progression. Beginning at
      birth, HIV-infected infants often have smaller size and lower birthweight than
      noninfected children born to HIV-infected women. The causes of growth
      dysregulation are varied, and can be due to alterations in gastrointestinal
      function, chronic or repetitive infections, and alterations in metabolic and
      endocrine function. The metabolic and endocrine effects may be the consequence of
      the primary infection or secondary to the use of any of the medications required
      to treat HIV infection and its complications. Correlational studies have
      identified an inverse relationship between viral burden and linear growth and
      body mass index, i.e., the use of antiviral medications that reduce viral burden
      is associated with improvements in anthropometric indices of growth. Alterations
      in cytokine profiles, possibly related to reported abnormalities in thyroid
      indices, fat metabolism, and the somatomedin axis, may be indicative of
      dysregulation on a cellular level. Pubertal delay, especially among boys, is
      common, and may contribute to the overall growth failure associated with HIV
      infection. If the basis for growth failure resides in metabolic and regulatory
      abnormalities, then interventions beyond increasing caloric intake will be
      necessary to increase linear growth rate and reverse growth failure in HIV
      infected children.

PMID- 8861929
TI  - Neurobehavioral manifestations of symptomatic HIV-1 disease in children: can
      nutritional factors play a role?
AB  - Central nervous system (CNS) abnormalities are significant and frequent
      complications of human immunodeficiency virus (HIV-1) infection in infants and
      children. Although the predominant cause of neurological and neuropsychological
      abnormalities appears to be related to HIV infection of the CNS, other factors
      including malnutrition may also play a role. We retrospectively evaluated the
      association of change in body weight with changes in neurocognitive function,
      ventricular brain ratio, and cerebrospinal quinolinic acid levels in a small
      cohort of children (n=15; mean age 6.3 years) with symptomatic HIV-1 disease
      before and after 6 months of antiretroviral therapy with continuous intravenous
      infusion of zidovudine (ZVD). Significant increases in weight and neurocognitive
      function as well as decreases in ventricular brain ratio and cerebrospinal
      quinolinic acid levels were noted after therapy. Only the relation between
      increase in weight and decrease in ventricular brain ratio was statistically
      significant (P< .01); contrary to expectations, an increase in weight seemed to
      correlate with a decrease in neurocognitive function (NS). Another group of
      children treated at the same time with oral intermittent ZVD, but otherwise
      receiving the same care did not show the same magnitude of improvement in
      neurocognitive function. These results seem to suggest that general supportive
      and medical care as well as nutritional factors may only play a limited role in
      the neurocognitive improvements after antiretroviral therapy with continuous
      infusion ZVD. Our sample size was, however, small and the nutritional measure
      rather global; thus these findings have to be considered as very preliminary.

PMID- 8861930
TI  - Neurological and developmental problems in pediatric HIV infection.
AB  - Human immunodeficiency virus type-1 (HIV-1)-associated neurologic disease, known
      as "HIV-1-associated progressive encephalopathy" (PE), is a common concomitant in
      the progression towards AIDS. PE, characterized by a triad of symptoms including
      impaired brain growth, progressive motor dysfunction, and loss or plateau of
      developmental milestones, is believed to result from both direct and indirect
      effects of HIV-1 infection on the central nervous system (CNS). Consequent to the
      hallmark systemic immune deficiency of HIV infection, the CNS becomes susceptible
      to opportunistic infections which add further morbidity and mortality, and may
      contribute either directly or indirectly to neurologic symptoms which can often
      mimic PE. Static encephalopathies (SE) represent fixed, nonprogressive neurologic
      or neurodevelopmental deficits in HIV-infected children. SE may or may not be
      caused by HIV infection but are often associated with such identifiable insults
      as prematurity, in utero exposure to toxins or infectious agents, or head trauma.
      Additional neurological manifestations of HIV infection are seizures,
      cerebrovascular complications (i.e., stroke), myelopathies, neuromuscular
      syndromes, and CNS complications of opportunistic infections. Neurobehavioral
      aberrations have also been observed in pediatric HIV infection. In addition to
      the neuropathogenesis, theories regarding the timing and detection of the
      neurological problems associated with pediatric HIV infection are discussed along
      with a presentation of current treatment paradigms and their rationales. The
      importance of identifying the numerous environmental factors, including
      nutritional status, that may confound the ability to discriminate between a
      primary or secondary role of HIV infection in the various neurological problems
      of HIV infection is discussed.

PMID- 8861931
TI  - Micronutrient and cytokine interaction in congenital pediatric HIV infection.
AB  - Malnutrition is a frequent manifestation of HIV infection that has received
      comparatively little attention despite growing clinical importance with improved
      treatment and lengthened survival times. Fundamental relationships and mechanisms
      of HIV viral interaction in nutrient metabolism remain to be established. In an
      attempt to begin to fill the void of information relative to pediatric HIV
      infection, we have summarized the extant knowledge with regard to micronutrients
      and present some of the data from studies performed in our laboratory. Previous
      studies have shown both that vitamin A deficiency is associated with increased
      mortality in HIV+ intravenous drug users and that maternal vitamin A deficiency
      is a risk factor for transmission in congenital exposure. Our most significant
      finding is that 70% of children congenitally exposed to HIV are vitamin A
      deficient in the first months of life compared to age-matched controls whether
      they are HIV-infected or not. About 25% of our patient population was found to
      have growth or developmental delay, frequently without other signs of progression
      and in the presence of an intact T-cell compartment. In addition, we found
      evidence of cytokine imbalance, specifically elevated plasma levels of TNF which
      has been implicated in loss of lean body mass. Inflammatory reactions in the
      mucosa and increased TNF production in association with regional HIV infection
      may compromise gastrointestinal absorption. Based on the review of the literature
      and our research findings, it is clear that understanding the interaction between
      nutrients and both the regional and systemic immune system is vital for
      intervention and effective nutrient repletion in congenital HIV infection.

PMID- 8861932
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Working group
      session report: setting the basic research agenda.

PMID- 8861933
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Working group
      session report: setting the clinical research agenda: domestic and international
      perspectives.

PMID- 8861934
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Working group
      session report: coordination of domestic and international effort in executing a
      research agenda in nutrition and pediatric HIV infection.

PMID- 8861935
TI  - Nutrition in pediatric HIV infection: setting the research agenda. Work group
      session report: priorities, recommendations, and strategies for supporting the
      research agenda.

PMID- 8861936
TI  - Nutrition in pediatric HIV infection: setting the research agenda; Work group
      session report: technology transfer.

PMID- 8861937
TI  - Crystal structure of delta9 stearoyl-acyl carrier protein desaturase from castor
      seed and its relationship to other di-iron proteins.
AB  - The three-dimensional structure of recombinant homodimeric delta9 stearoyl-acyl
      carrier protein desaturase, the archetype of the soluble plant fatty acid
      desaturases that convert saturated to unsaturated fatty acids, has been
      determined by protein crystallographic methods to a resolution of 2.4 angstroms.
      The structure was solved by a combination of single isomorphous replacement,
      anomalous contribution from the iron atoms to the native diffraction data and 6
      fold non-crystallographic symmetry averaging. The 363 amino acid monomer consists
      of a single domain of 11 alpha-helices. Nine of these form an antiparallel helix
      bundle. The enzyme subunit contains a di-iron centre, with ligands from four of
      the alpha-helices in the helix bundle. The iron ions are bound in a highly
      symmetric environment, with one of the irons forming interactions with the side
      chains of E196 and H232 and the second iron with the side chains of E105 and
      H146. Two additional glutamic acid side chains, from E143 and E229, are within
      coordination distance to both iron ions. A water molecule is found within the
      second coordination sphere from the iron atoms. The lack of electron density
      corresponding to a mu-oxo bridge, and the long (4.2 angstroms) distance between
      the iron ions suggests that this probably represents the diferrous form of the
      enzyme. A deep channel which probably binds the fatty acid extends from the
      surface into the interior of the enzyme. Modelling of the substrate, stearic
      acid, into this channel places the delta9 carbon atom in the vicinity of one of
      the iron ions.

PMID- 8861938
TI  - Identification of a titratable lysine residue that determines sensitivity of
      kidney potassium channels (ROMK) to intracellular pH.
AB  - Potassium (K+) homeostasis is controlled by the secretion of K+ ions across the
      apical membrane of renal collecting duct cells through a low-conductance inwardly
      rectifying K+ channel. The sensitivity of this channel to intracellular pH is
      particularly high and assumed to play a key role in K+ homeostasis. Recently, the
      apical K+ channel has been cloned (ROMK1,2,3 = Kir1.1a, Kir1.1b and Kir1.1c) and
      the pH dependence of ROMK1 was shown to resemble closely that of the native
      apical K+ channel. It is reported here that the steep pH dependence of ROMK
      channels is determined by a single amino acid residue located in the N-terminus
      close to the first hydrophobic segment M1. Changing lysine (K) at position 80 to
      methionine (M) removed the sensitivity of ROMK1 channels to intracellular pH. In
      pH-insensitive IRK1 channels, the reverse mutation (M84K) introduced dependence
      on intracellular pH similar to that of ROMK1 wild-type. A detailed mutation
      analysis suggests that a shift in the apparent pKalpha of K80 underlies the pH
      regulation of ROMK1 channels in the physiological pH range.

PMID- 8861939
TI  - Functional interaction of syntaxin and SNAP-25 with voltage-sensitive L- and N
      type Ca2+ channels.
AB  - We have used an electrophysiological assay to investigate the functional
      interaction of syntaxin 1A and SNAP-25 with the class C, L-type, and the class B,
      N-type, voltage-sensitive calcium channels. Co-expression of syntaxin 1A with the
      pore-forming subunits of the L- and N-type channels in Xenopus oocytes generates
      a dramatic inhibition of inward currents (>60%) and modifies the rate of
      inactivation (tau) and steady-state voltage dependence of inactivation. Syntaxin
      1-267, which lacks the transmembrane region (TMR), and syntaxin 2 do not modify
      channel properties, suggesting that the syntaxin 1A interaction site resides
      predominantly in the TMR. Co-expression of SNAP-25 significantly modifies the
      gating properties of L- and N-type channels and displays modest inhibition of
      current amplitude. Syntaxin 1A and SNAP-25 combined restore the syntaxin
      inhibited N-type inward current but not the reduced rate of inactivation. Hence,
      a distinct interaction of a putative syntaxin 1A-SNAP-25 complex with the channel
      is apparent, consistent with the formation of a synaptosomal SNAP receptors
      (SNAREs) complex. The in vivo functional reconstitution: (i) establishes the
      proximity of the SNAREs to calcium channels; (ii) provides new insight into a
      potential regulatory role for the two SNAREs in controlling calcium influx
      through N- and L-type channels; and (iii) may suggest a pivotal role for calcium
      channels in the secretion process.

PMID- 8861940
TI  - hch-1, a gene required for normal hatching and normal migration of a neuroblast
      in C. elegans, encodes a protein related to TOLLOID and BMP-1.
AB  - Proteins of the tolloid/bone morphogenetic protein (BMP)-1 family play important
      roles in the differentiation of cell fates. Among those proteins are BMP-1, which
      plays a role in cartilage and bone formation in mammals, the TOLLOID protein,
      which is required for the establishment of the dorsoventral axis of Drosophila
      embryos and BP10/SpAN, which are thought to act in the morphogenesis of sea
      urchins. These proteins have some properties in common. First, they contain the
      astacin metalloprotease domain, the CUB domain and the epidermal growth factor
      like domain. Second, they are expressed in embryos at stages expected for their
      role in cell differentiation. Third, at least BMP-1 and TOLLOID are thought to
      interact with proteins of the transforming growth factor-beta family. We report
      that the hch-1 gene of the nematode Caenorhabditis elegans encodes a tolloid/BMP
      1 family protein. The protein has the characteristic domains common to the
      tolloid/ BMP-1 family. Like other members of the family, it is expressed in
      embryos. However, the phenotype of hch-1 mutants shows that it is required for
      normal hatching and normal migration of a post-embryonic neuroblast. Furthermore,
      in spite of its expression in embryogenesis, it is not required for the viability
      of embryos. These results show new functions of the tolloid/BMP-1 family proteins
      and give insight into their evolution.

PMID- 8861941
TI  - The scl gene product is required for the generation of all hematopoietic lineages
      in the adult mouse.
AB  - Homozygosity for a null mutation in the scl gene causes mid-gestational embryonic
      lethality in the mouse due to failure of development of primitive hematopoiesis.
      Whilst this observation established the role of the scl gene product in primitive
      hematopoiesis, the death of the scl null embryos precluded analysis of the role
      of scl in later hematopoietic development. To address this question, we created
      embryonic stem cell lines with a homozygous null mutation of the scl gene (scl-/
      ) and used these lines to derive chimeric mice. Analysis of the chimeric mice
      demonstrates that the scl-/- embryonic stem cells make a substantial contribution
      to all non-hematopoietic tissues but do not contribute to any hematopoietic
      lineage. These observations reveal a crucial role for the scl gene product in
      definitive hematopoiesis. In addition, in vitro differentiation assays with scl-/
      embryonic stem cells showed that the scl gene product was also required for
      formation of hematopoietic cells in this system.

PMID- 8861942
TI  - Bcl-2 mutants with restricted subcellular location reveal spatially distinct
      pathways for apoptosis in different cell types.
AB  - Human Bcl-2 is located in multiple intracellular membranes when expressed in MDCK
      and Rat-1/myc cells. We restricted expression to the endoplasmic reticulum or
      mitochondria by exchanging the Bcl-2 carboxy-terminal insertion sequence for an
      equivalent sequence from cytochrome b5 or ActA, respectively. MDCK cells are
      protected from serum deprivation-induced apoptosis by both wild-type Bcl-2 and
      the mutant targeted to mitochondria but not by the mutant targeted to endoplasmic
      reticulum. In contrast, when expressed in Rat-1/myc cells, the Bcl-2 mutant
      located at the endoplasmic reticulum is more effective than that targeted to
      mitochondria. In MDCK cells both mutants bind Bax as effectively as wild-type,
      demonstrating that Bax binding is not sufficient to prevent apoptosis.

PMID- 8861943
TI  - RXRalpha-null F9 embryonal carcinoma cells are resistant to the differentiation,
      anti-proliferative and apoptotic effects of retinoids.
AB  - The F9 murine embryonal carcinoma (EC) cell line, a well established model system
      for the study of retinoic acid (RA)-induced differentiation, differentiates into
      cells resembling three types of extra-embryonic endoderm (primitive, parietal and
      visceral), depending on the culture conditions and RA concentration used. A
      number of previously identified genes are differentially expressed during this
      process and serve as markers for the different endodermal cell types.
      Differentiation is also accompanied by a decreased rate of proliferation and an
      apoptotic response. Using homologous recombination, we have disrupted both
      alleles of the retinoid X receptor (RXR) alpha gene in F9 cells to investigate
      its role in mediating these responses. The loss of RXRalpha expression impaired
      the morphological differentiation of F9 EC cells into primitive and parietal
      endoderm, but has little effect on visceral endodermal differentiation.
      Concomitantly the inducibility of most primitive and parietal endoderm
      differentiation-specific genes was impaired, while several genes upregulated
      during visceral endodermal differentiation were induced normally. We also
      demonstrate that RXRalpha is required for both the anti-proliferative and
      apoptotic responses in RA-treated F9 cells. Additionally, we provide further
      evidence that retinoic acid receptor (RAR)-RXR heterodimers are the functional
      units transducing the effects of retinoids in F9 cells.

PMID- 8861944
TI  - Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress-
      and cytokine-stimulated monocytes and epithelial cells.
AB  - Two chromatographically distinct stress-activated protein kinase kinases (SAPKKs)
      have been identified in several mammalian cells, termed SAPKK2 and SAPKK3, which
      activate the MAP kinase family member RK/p38 but not JNK/SAPK in vitro. Here we
      demonstrate that SAPKK2 is identical or very closely related to the MAP kinase
      kinase family member MKK3. However, under our assay conditions, SAPKK3 was the
      major activator of RK/p38 detected in extracts prepared from stress- or
      interleukin-1-stimulated epithelial (KB) cells, from bacterial lipopolysaccharide
      and tumour necrosis factor alpha-stimulated THP1 monocytes or from rabbit
      skeletal muscle. The activated form of SAPKK3 was purified from muscle to near
      homogeneity, and tryptic peptide sequences were used to clone human and murine
      cDNAs encoding this enzyme. Human SAPKK3 comprised 334 amino acids and was 78%
      identical to MKK3. The murine and human SAPKK3 were 97% identical in their amino
      acid sequences. We also cloned a different murine cDNA that appears to encode a
      SAPKK3 protein truncated at the N-terminus. SAPKK3 is identical to the recently
      cloned MKK6.

PMID- 8861945
TI  - The receptor-associated protein (RAP) binds calmodulin and is phosphorylated by
      calmodulin-dependent kinase II.
AB  - The receptor-associated protein, RAP, is an intracellular protein that may
      function as a chaperone for the LDL-receptor family receptors. Here we report
      calmodulin as the first identified RAP binding protein outside of the LDL
      receptor family members. We demonstrate that RAP binds calmodulin in a Ca2+- and
      pH-dependent manner characteristic of calmodulin-dependent enzymes, and present
      evidence that RAP is a substrate for calmodulin-dependent enzymes. Thus, CaM
      kinase II and calcineurin readily phosphorylate and dephosphorylate,
      respectively, serine residues in RAP, and in the individual RAP domains D2 (amino
      acids 113-218) and D3 (amino acids 219-323) which both contain sites for CaM
      kinase II-mediated phosphorylation and for calmodulin binding. In addition, we
      provide evidence that RAP is phosphorylated by other kinases such as casein
      kinase II. Studies of 32[ortho]P-labelled cell cultures demonstrate that RAP is
      phosphorylated in vivo. Our results suggest that RAP may have hitherto unknown
      functions implicating phosphorylation and calmodulin-mediated modulation.

PMID- 8861946
TI  - Erythropoietin-induced erythroid differentiation of the human erythroleukemia
      cell line TF-1 correlates with impaired STAT5 activation.
AB  - The TF-1 cell line has been established from a patient with erythroleukemia.
      While various cytokines induce TF-1 cell proliferation, erythropoietin (Epo) only
      sustains the short-term growth of these cells and induces their differentiation
      along the erythroid lineage. A truncated Epo receptor (EpoR) is overexpressed in
      these cells. The truncation removed the 96 C-terminal amino acids, including
      seven tyrosine residues. An additional single mutation at position +3 of Tyr344
      led to the replacement of leucine 347 by proline. Stimulation by Epo induced an
      impaired activation of the STAT5 transcription factor in these cells. The same
      defect in STAT5 activation was found in the murine FDCP-1 cell line transfected
      with a chimeric EpoR containing the abnormal TF-1 EpoR cytoplasmic domain.
      Infection of TF-1 cells with a retrovirus containing a normal murine EpoR was
      able to restore both Epo-induced STAT5 activity and cellular proliferation. In
      contrast, Epo-induced differentiation was reduced strongly in infected TF-1ER
      cells. These results suggest that Epo-induced differentiation correlates with
      impaired Epo-induced STAT5 activation.

PMID- 8861947
TI  - Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and
      ubiquitin-dependent degradation of cyclin E.
AB  - A yeast screen was developed to identify mutations in human cyclin E that lead to
      stabilization of the protein in order to identify determinants important for
      cyclin E turnover. Both C-terminal truncations and missense mutations near the C
      terminus of cyclin E conferred hyperstability in vivo, suggesting that sequences
      in this region were critical for turnover. The following observations indicate
      that autophosphorylation of CDK2/cyclin E on Thr380 of the cyclin regulates
      cyclin E destruction: (i) mutation of Thr380 to Ala stabilizes cyclin E in yeast
      and mammalian cells; (ii) cyclin E/CDK2 autophosphorylates on cyclin E in vitro
      and cyclin E is a phosphoprotein in vivo in mammalian cells; (iii) the T380A
      mutation eliminates phosphorylation on the same site in mammalian cells and in
      vitro; (iv) inhibiting CDK2 activity in vivo stabilizes cyclin E; (v) the T380A
      mutation prevents ubiquitination of cyclin E. These results suggest a model where
      activation of cyclinE/CDK2 is coupled to cyclin E turnover via site-specific
      phosphorylation, which acts as a signal for ubiquitination and proteasome
      processing.

PMID- 8861948
TI  - DAG, a gene required for chloroplast differentiation and palisade development in
      Antirrhinum majus.
AB  - We have identified a mutation at the DAG locus of Antirrhinum majus which blocks
      the development of chloroplasts to give white leaves with green revertant
      sectors. The green areas contain normal chloroplasts whereas the white areas have
      small plastids that resemble proplastids. The cotyledons of dark-grown dag mutant
      seedlings have plastids which also resemble proplastids. The palisade cells in
      the white areas of dag mutant leaves also lack their characteristic columnar
      shape. The DAG locus was cloned by transposon tagging: DAG encodes a novel
      protein with a predicted Mr of 26k, which is targeted to the plastids. Cleavage
      of its predicted transit peptide gives a mature protein of Mr 20k. Screening of
      databases and analysis of Southern blots gave evidence that DAG belongs to a
      protein family with homology to several proteins of unknown function from plants.
      Expression of DAG is required for expression of nuclear genes affecting the
      chloroplasts, such as CAB and RBCS, and also for expression of the plastidial
      gene RPOB encoding the plastidial RNA polymerase beta subunit, indicating that it
      functions very early in chloroplast development.

PMID- 8861949
TI  - The DCL gene of tomato is required for chloroplast development and palisade cell
      morphogenesis in leaves.
AB  - The defective chloroplasts and leaves-mutable (dcl-m) mutation of tomato was
      identified in a Ds mutagenesis screen. This unstable mutation affects both
      chloroplast development and palisade cell morphogenesis in leaves. Mutant plants
      are clonally variegated as a result of somatic excision of Ds and have albino
      leaves with green sectors. Leaf midribs and stems are light green with sectors of
      dark green tissue but fruit and petals are wild-type in appearance. Within dark
      green sectors of dcl-m leaves, palisade cells are normal, whereas in albino areas
      of dcl-m leaves, palisade cells do not expand to become their characteristic
      columnar shape. The development of chloroplasts from proplastids in albino areas
      is apparently blocked at an early stage. DCL was cloned using Ds as a tag and
      encodes a novel protein of approximately 25 kDa, containing a chloroplast transit
      peptide and an acidic alpha-helical region. DCL protein was imported into
      chloroplasts in vitro and processed to a mature form. Because of the ubiquitous
      expression of DCL and the proplastid-like appearance of dcl-affected plastids,
      the DCL protein may regulate a basic and universal function of the plastid. The
      novel dcl-m phenotype suggests that chloroplast development is required for
      correct palisade cell morphogenesis during leaf development.

PMID- 8861950
TI  - AAA proteases with catalytic sites on opposite membrane surfaces comprise a
      proteolytic system for the ATP-dependent degradation of inner membrane proteins
      in mitochondria.
AB  - The mechanism of selective protein degradation of membrane proteins in
      mitochondria has been studied employing a model protein that is subject to rapid
      proteolysis within the inner membrane. Protein degradation was mediated by two
      different proteases: (i) the m-AAA protease, a protease complex consisting of
      multiple copies of the ATP-dependent metallopeptidases Yta1Op (Afg3p) and Yta12p
      (Rcalp); and (ii) by Ymelp (Ytallp) that also is embedded in the inner membrane.
      Ymelp, highly homologous to Yta1Op and Yta12p, forms a complex of approximately
      850 kDa in the inner membrane and exerts ATP-dependent metallopeptidase activity.
      While the m-AAA protease exposes catalytic sites to the mitochondrial matrix,
      Ymelp is active in the intermembrane space. The Ymelp complex was therefore
      termed 'i-AAA protease'. Analysis of the proteolytic fragments indicated cleavage
      of the model polypeptide at the inner and outer membrane surface and within the
      membrane-spanning domain. Thus, two AAA proteases with their catalytic sites on
      opposite membrane surfaces constitute a novel proteolytic system for the
      degradation of membrane proteins in mitochondria.

PMID- 8861951
TI  - Topology of IEP110, a component of the chloroplastic protein import machinery
      present in the inner envelope membrane.
AB  - Proteins from both the inner and outer envelope membranes are engaged in the
      recognition and translocation of precursor proteins into chloroplasts. A 110 kDa
      protein of the chloroplastic inner envelope membrane was identified as a
      component of the protein import apparatus by two methods. First, this protein was
      part of a 600 kDa complex generated by cross-linking of precursors trapped in the
      translocation process. Second, solubilization with detergents of chloroplasts
      containing trapped precursors resulted in the identification of a complex
      containing both radiolabeled precursor and IEP110. Trypsin treatment of intact
      purified chloroplasts was used to study the topology of IEP110. The protease
      treatment left the inner membrane intact while simultaneously degrading domains
      of inner envelope proteins exposed to the intermembrane space. About 90 kDa of
      IEP110 was proteolitically removed, indicating that large portions protrude into
      the intermembrane space. Hydropathy analysis of the protein sequence deduced from
      the isolated cDNA clone in addition to Western blot analysis using an antiserum
      of IEP110 specific to the N-terminal 20 kDa, suggests that the N-terminus serves
      to anchor the protein in the membrane. We speculate that IEP110 could be involved
      in the formation of translocation contact sites due to its specific topology.

PMID- 8861952
TI  - Multidrug resistance in Lactococcus lactis: evidence for ATP-dependent drug
      extrusion from the inner leaflet of the cytoplasmic membrane.
AB  - Lactococcus lactis possesses an ATP-dependent drug extrusion system which shares
      functional properties with the mammalian multidrug resistance (MDR) transporter P
      glycoprotein. One of the intriguing aspects of both transporters is their ability
      to interact with a broad range of structurally unrelated amphiphilic compounds.
      It has been suggested that P-glycoprotein removes drugs directly from the
      membrane. Evidence is presented that this model is correct for the lactococcal
      multidrug transporter through studies of the extrusion mechanism of BCECF-AM and
      cationic diphenylhexatriene (DPH) derivatives from the membrane. The non
      fluorescent probe BCECF-AM can be converted intracellularly into its fluorescent
      derivative, BCECF, by non-specific esterase activities. The development of
      fluorescence was decreased upon energization of the cells. These and kinetic
      studies showed that BCECF-AM is actively extruded from the membrane before it can
      be hydrolysed intracellularly. The increase in fluorescence intensity due to the
      distribution of TMA-DPH into the phospholipid bilayer is a biphasic process. This
      behaviour reflects the fast entry of TMA-DPH into the outer leaflet followed by a
      slower transbilayer movement to the inner leaflet of the membrane. The initial
      rate of TMA-DPH extrusion correlates with the amount of probe associated with the
      inner leaflet. Taken together, these results demonstrate that the lactococcal MDR
      transporter functions as a 'hydrophobic vacuum cleaner', expelling drugs from the
      inner leaflet of the lipid bilayer. Thus, the ability of amphiphilic substrates
      to partition in the inner leaflet of the membrane is a prerequisite for
      recognition by multidrug transporters.

PMID- 8861953
TI  - Imaging the intracellular trafficking and state of the AB5 quaternary structure
      of cholera toxin.
AB  - The subcellular localization and corresponding quaternary state of fluorescent
      labelled cholera toxin were determined at different time points after exposure to
      living cells by a novel form of fluorescence confocal microscopy. The
      compartmentalization and locus of separation of the pentameric B subunits (CTB)
      from the A subunit (CTA) of the toxin were evaluated on a pixel-by-pixel (voxel
      by-voxel) basis by measuring the fluorescence resonance energy transfer (FRET)
      between CTB labelled with the sulfoindocyanine dye Cy3 and an antibody against
      CTA labelled with Cy5. The FRET efficiency was determined by a new technique
      based on the release of quenching of the Cy3 donor after photodestruction of the
      Cy5 acceptor in a region of interest within the cell. The results demonstrate
      vesicular transport of the holotoxin from the plasma membrane to the Golgi
      compartment with subsequent separation of the CTA and CTB subunits. The CTA
      subunit is redirected to the plasma membrane by retrograde transport via the
      endoplasmic reticulum whereas the CTB subunit persists in the Golgi compartment.

PMID- 8861954
TI  - PIG-B, a membrane protein of the endoplasmic reticulum with a large lumenal
      domain, is involved in transferring the third mannose of the GPI anchor.
AB  - Many eukaryotic cell surface proteins are bound to the membrane via the
      glycosylphosphatidylinositol (GPI) anchor that is covalently linked to their
      carboxy-terminus. The GPI anchor precursor is synthesized in the endoplasmic
      reticulum (ER) and post-translationally linked to protein. We cloned a human gene
      termed PIG-B (phosphatidylinositol glycan of complementation class B) that is
      involved in transferring the third mannose. PIG-B encodes a 554 amino acid, ER
      transmembrane protein with an amino-terminal portion of approximately 60 amino
      acids on the cytoplasmic side and a large carboxy-terminal portion of 470 amino
      acids within the ER lumen. A mutant PIG-B lacking the cytoplasmic portion remains
      active, indicating that the functional site of PIG-B resides on the lumenal side
      of the ER membrane. The PIG-B gene was localized to chromosome 15 at q21-q22.
      This autosomal location would explain why PIG-B is not involved in the defective
      GPI anchor synthesis in paroxysmal nocturnal hemoglobinuria, which is always
      caused by a somatic mutation of the X-linked PIG-A gene.

PMID- 8861955
TI  - p619, a giant protein related to the chromosome condensation regulator RCC1,
      stimulates guanine nucleotide exchange on ARF1 and Rab proteins.
AB  - We report the identification of a novel human gene, designated p619, that encodes
      a polypeptide of 4861 amino acid residues, one of the largest human proteins
      known to date. The p619 protein contains two regions of seven internal repeats
      highly related to the cell cycle regulator RCC1, a guanine nucleotide exchange
      factor for the small GTP binding protein, Ran. In addition, p619 possesses seven
      beta-repeat domains characteristic of the beta-subunit of heterotrimeric G
      proteins, three putative SH3 binding sites, seven polar amino acid-rich regions,
      a putative leucine zipper and a carboxy-terminal HECT domain characteristic of E3
      ubiquitin-protein ligases. p619 is expressed ubiquitously in mouse and human
      tissues and overexpressed in several human tumor cell lines. Subcellular
      localization studies indicate that p619 is located in the cytosol and in the
      Golgi apparatus. Localization of p619 in the Golgi is altered by Brefeldin A. The
      carboxy-terminal RCC1-like domain of p619 interacts specifically with
      myristoylated ARF1, a small GTP binding protein also located in the Golgi.
      Moreover, the second RCC1-like motif located at the amino-terminus of p619
      stimulates guanine nucleotide exchange on ARF1 and on members of the related Rab
      proteins, but not on other small GTP binding proteins such as Ran or R-Ras2/TC21.
      These observations suggest that p619 is a Brefeldin A-sensitive Golgi protein
      that functions as a guanine nucleotide exchange factor for ARF1 and, possibly,
      for members of the Rab family of proteins.

PMID- 8861956
TI  - A novel class of small amphipathic peptides affect aerial hyphal growth and
      surface hydrophobicity in Ustilago maydis.
AB  - Ustilago maydis, a fungal pathogen of corn, can alternate between yeast-like and
      filamentous growth. This dimorphic switch is governed by the mating-type loci. We
      have identified an abundant class of small SDS-insoluble cell wall proteins,
      designated repellents, specifically present in the filamentous form. Genetic
      analysis revealed that these peptides are processed from a single precursor
      protein, Rep1. Rep1 comprises 652 amino acids with a leader sequence for
      secretion. A characteristic feature of Rep1 is 12 repeats of a 37 amino acid
      consensus sequence; 10 of these repeats are separated by Kex2 protease cleavage
      sites. In (delta)rep1 mutants formation of aerial hyphae and surface
      hydrophobicity were reduced dramatically. This and the fact that expression of
      rep1 is regulated by the mating-type loci indicates that repellents play a
      structural role in the formation of aerial hyphae.

PMID- 8861957
TI  - Identification of a surface glycoprotein on African green monkey kidney cells as
      a receptor for hepatitis A virus.
AB  - Very little is known about the mechanism of cell entry of hepatitis A virus
      (HAV), and the identification of cellular receptors for this picornavirus has
      been elusive. Here we describe the molecular cloning of a cellular receptor for
      HAV using protective monoclonal antibodies raised against susceptible African
      green monkey kidney (AGMK) cells as probes. Monoclonal antibodies 190/4, 235/4
      and 263/6, which reacted against similar epitopes, specifically protected AGMK
      cells against HAV infection by blocking the binding of HAV. Expression cloning
      and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a
      novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the
      HAV cellular receptor 1 (HAVcr-1). Immunofluorescence analysis indicated that
      mouse Ltk- cells transfected with HAVcr-1 cDNA gained limited susceptibility to
      HAV infection, which was blocked by treatment with monoclonal antibody 190/4. Our
      results demonstrate that the HAVcr-1 polypeptide is an attachment receptor for
      HAV and strongly suggest that it is also a functional receptor which mediates HAV
      infection. This report constitutes the first identification of a cellular
      receptor for HAV.

PMID- 8861958
TI  - PAX8-mediated activation of the wt1 tumor suppressor gene.
AB  - The developing renal system has long been exploited to study the regulation of
      gene expression during mesenchymal-epithelial transitions. Several transcription
      factors, including WT1 and PAX8, are expressed early in nephrogenesis and play a
      key role in this process. The expression of PAX8 occurs in the induced mesenchyme
      of the developing kidney prior to the upregulation of WT1 levels in the same
      cells. In this report, we assessed whether the Pax-8 gene product resides
      upstream of wt1 in a common regulatory pathway. Transfection studies, as well as
      gel-shift assays, indicate that PAX8 transactivates wt1 through elements within a
      38 bp conserved motif, present in human and murine promoters. Two PAX8 isoforms,
      generated by alternative splicing at the C-terminus and previously thought to
      lack transactivation potential, were found to be capable of activating wt1
      expression. We also demonstrate that the endogenous wt1 promoter can be
      upregulated by exogenously supplied PAX8, suggesting that a function of PAX8
      during mesenchymal--epithelial cell transition in renal development is to induce
      wt1 gene expression.

PMID- 8861959
TI  - Thyroid hormone-dependent transcriptional repression of neural cell adhesion
      molecule during brain maturation.
AB  - Thyroid hormone (T3) is a main regulator of brain development acting as a
      transcriptional modulator. However, only a few T3-regulated brain genes are
      known. Using an improved whole genome PCR approach, we have isolated seven clones
      encoding sequences expressed in neonatal rat brain which are under the
      transcriptional control of T3. Six of them, including the neural cell adhesion
      molecule NCAM, alpha-tubulin and four other unidentified sequences (RBA3, RBA4,
      RBB3 and RBB5) were found to be upregulated in the hypothyroid brain, whereas
      another (RBE7) was downregulated. Binding sites for the T3 receptor (T3R/c-erbA)
      were identified in the isolated clones by gel-shift and footprinting assays.
      Sites in the NCAM (in an intron), alpha-tubulin (in an exon) and RBA4 clones
      mediated transcriptional regulation by T3 when inserted upstream of a reporter
      construct. However, no effect of the NCAM clone was found when located downstream
      of another reporter gene. Northern blotting and in situ hybridization studies
      showed a higher expression of NCAM in the brain of postnatal hypothyroid rats.
      Since NCAM is an important morphoregulatory molecule, abnormal NCAM expression is
      likely to contribute to the alterations present in the brain of thyroid-deficient
      humans and experimental animals.

PMID- 8861960
TI  - The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine
      pancreas-specific basic helix-loop-helix protein.
AB  - We report the isolation of cDNA for the p48 DNA-binding subunit of the
      heterooligomeric transcription factor PTF1. A sequence analysis of the cDNA
      demonstrates that p48 is a new member of the family of basic helix-loop-helix
      (bHLH) transcription factors. The p48 bHLH domain shows striking amino acid
      sequence similarity with the bHLH domain of proteins that act as developmental
      regulators, including the twist gene product, myogenic factors and proteins
      involved in hematopoietic differentiation. We show that reduced p48 synthesis
      correlates with a diminished expression of genes encoding exocrine pancreas
      specific functions. The synthesis of p48 mRNAs, and therefore also the protein,
      is restricted to cells of the exocrine pancreas in the adult and to the
      pancreatic primordium in the embryo. Thus the pancreas-specific DNA-binding
      activity of PTF1 originates from the synthesis of at least one cell-specific
      component rather than from a cell-specific assembly of more widely distributed
      proteins.

PMID- 8861961
TI  - Multiple interactions amongst floral homeotic MADS box proteins.
AB  - Most known floral homeotic genes belong to the MADS box family and their products
      act in combination to specify floral organ identity by an unknown mechanism. We
      have used a yeast two-hybrid system to investigate the network of interactions
      between the Antirrhinum organ identity gene products. Selective
      heterodimerization is observed between MADS box factors. Exclusive interactions
      are detected between two factors, DEFICIENS (DEF) and GLOBOSA (GLO), previously
      known to heterodimerize and control development of petals and stamens. In
      contrast, a third factor, PLENA (PLE), which is required for reproductive organ
      development, can interact with the products of MADS box genes expressed at early,
      intermediate and late stages. We also demonstrate that heterodimerization of DEF
      and GLO requires the K box, a domain not found in non-plant MADS box factors,
      indicating that the plant MADS box factors may have different criteria for
      interaction. The association of PLENA and the temporally intermediate MADS box
      factors suggests that part of their function in mediating between the meristem
      and organ identity genes is accomplished through direct interaction. These data
      reveal an unexpectedly complex network of interactions between the factors
      controlling flower development and have implications for the determination of
      organ identity.

PMID- 8861963
TI  - Transcription factor recognition surface on the RNA polymerase alpha subunit is
      involved in contact with the DNA enhancer element.
AB  - The carboxy-terminal one-third of Escherichia coli RNA polymerase alpha subunit
      plays a key role in transcription regulation by a group of protein transcription
      factors and DNA enhancer (UP) elements. The roles of individual amino acid
      residues within this regulatory domain of the alpha subunit were examined after
      systematic mutagenesis of the putative contact regions (residues 258-275 and 297
      298) for the cAMP receptor protein (CRP). The reconstituted RNA polymerases
      containing the mutant alpha subunits were examined for their response to
      transcription activation by cAMP-CRP and the rrnBP1 UP element. Mutations
      affecting CRP responsiveness were located on the surface of the putative CRP
      contact helix and most of these mutations also influenced the response to the
      rrnB UP element. These observations raise the possibility that the CRP contact
      surface is also involved in contact with the DNA UP element, although some amino
      acid residues within this region play different roles in molecular communication
      with CRP and the UP element. Among the amino acid residues constituting the
      contact surface, Arg265 was found to play a major role in response to both CRP
      and the DNA UP element. Judged by DNase I footprinting analysis, alpha mutants
      defective in transcription from the CRP-dependent lacP1 promoter showed decreased
      activity in the cooperative binding of CRP. Likewise, mutants defective in rrnBP1
      transcription showed decreased binding to the UP element. The amino acid residues
      important for contact with both CRP and DNA are conserved in the alpha subunits
      of not only bacterial, but also chloroplast RNA polymerases.

PMID- 8861962
TI  - Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box
      related sites in vivo.
AB  - The c-Myc protein is involved in cell proliferation, differentiation and
      apoptosis though heterodimerization with Max to form a transcriptionally active
      sequence-specific DNA binding complex. By means of sequential immunoprecipitation
      of chromatin using anti-Max and anti-Myc antibodies, we have identified a Myc
      regulated gene and genomic sites occupied by Myc-Max in vivo. Four of 27 sites
      recovered by this procedure corresponded to the highest affinity 'canonical'
      CACGTG sequence. However, the most common in vivo binding sites belonged to the
      group of 'non-canonical' E box-related binding sites previously identified by in
      vitro selection. Several of the genomic fragments isolated contained transcribed
      sequences, including one, MrDb, encoding an evolutionarily conserved RNA helicase
      of the DEAD box family. The corresponding mRNA was induced following activation
      of a Myc-estrogen receptor fusion protein (Myc-ER) in the presence of a protein
      synthesis inhibitor, consistent with this helicase gene being a direct target of
      Myc-Max. In addition, as for c-Myc, the expression of MrDb is induced upon
      proliferative stimulation of primary human fibroblasts as well as B cells and
      down-regulated during terminal differentiation of HL60 leukemia cells. Our
      results indicate that Myc-Max heterodimers interact in vivo with a specific set
      of E box-related DNA sequences and that Myc is likely to activate multiple target
      genes including a highly conserved DEAD box protein. Therefore, Myc may exert its
      effects on cell behavior through proteins that affect RNA structure and
      metabolism.

PMID- 8861964
TI  - Transcriptional pulse-chase analysis reveals a role for a novel snRNP-associated
      protein in the manufacture of spliceosomal snRNPs.
AB  - Vertebrate spliceosomal snRNAs associate with a conserved set of proteins, the Sm
      proteins, via a conserved RNA sequence, the Sm site. Assembly of this complex is
      required for the accumulation of stable snRNPs, hypermethylation of the 5' cap
      structure and nuclear import of the resultant particles. The function of
      individual core snRNP proteins is poorly understood, in part because of the
      difficulty of selectively inactivating individual polypeptides in vivo. Using a
      transcriptional pulse-chase method we have defined for the first time the steps
      of snRNP biogenesis in Saccharomyces cerevisiae. We describe a novel component of
      spliceosomal snRNPs, Brr1, which is distinct in sequence from Sm core proteins
      and yet which shares many of their properties, as well as a genetic interaction
      with the yeast homolog of Sm D1 core protein. Through a kinetic analysis of snRNP
      formation in wild-type and brr1 mutant cells we demonstrate specific defects in a
      subset of steps in the brr1 mutant: newly synthesized snRNAs are destabilized and
      3'-end processing is slowed, whereas the cap hypermethylation reaction is
      unaffected. Notably, the stability of mature particles, as measured by promoter
      shut-off experiments, is normal in the absence of the Brr1 snRNP protein.

PMID- 8861965
TI  - Spliced leader RNA of trypanosomes: in vivo mutational analysis reveals extensive
      and distinct requirements for trans splicing and cap4 formation.
AB  - In trypanosomes mRNAs are generated through trans splicing. The spliced leader
      (SL) RNA, which donates the 5'-terminal mini-exon to each of the protein coding
      exons, plays a central role in the trans splicing process. We have established in
      vivo assays to study in detail trans splicing, cap4 modification, and RNP
      assembly of the SL RNA in the trypanosomatid species Leptomonas seymouri. First,
      we found that extensive sequences within the mini-exon are required for SL RNA
      function in vivo, although a conserved length of 39 nt is not essential. In
      contrast, the intron sequence appears to be surprisingly tolerant to mutation;
      only the stem-loop II structure is indispensable. The asymmetry of the sequence
      requirements in the stem I region suggests that this domain may exist in
      different functional conformations. Second, distinct mini-exon sequences outside
      the modification site are important for efficient cap4 formation. Third, all SL
      RNA mutations tested allowed core RNP assembly, suggesting flexible requirements
      for core protein binding. In sum, the results of our mutational analysis provide
      evidence for a discrete domain structure of the SL RNA and help to explain the
      strong phylogenetic conservation of the mini-exon sequence and of the overall SL
      RNA secondary structure; they also suggest that there may be certain differences
      between trans splicing in nematodes and trypanosomes. This approach provides a
      basis for studying RNA-RNA interactions in the trans spliceosome.

PMID- 8861966
TI  - Translational regulation of human p53 gene expression.
AB  - In blast cells obtained from patients with acute myelogenous leukemia, p53 mRNA
      was present in all the samples examined while the expression of p53 protein was
      variable from patient to patient. Mutations in the p53 gene are infrequent in
      this disease and, hence, variable protein expression in the majority of the
      samples cannot be accounted for by mutation. In this study, we examined the
      regulation of p53 gene expression in human leukemic blasts and characterized the
      p53 transcripts in these cells. We found control both at the level of RNA
      abundance and at the level of translation. Four experiments point towards
      translational control of human p53 gene expression. First, there is no
      correlation between the level of p53 mRNA and the level of p53 protein expression
      in blast cells. Second, in two cell lines with similar levels of p53 protein
      expression but with different levels of p53 mRNA, we find that there is
      preferential association of p53 mRNA with large polysomes in the cells with less
      p53 RNA. Third, translation of synthetic human p53 transcripts in cell-free
      extracts is inhibited by the p53 3'UTR. Fourth, the p53 3'UTR, when present in
      cis, can repress translation of a heterologous transcript. These observations
      raise the possibility that human p53 mRNA translation may be regulated in vivo by
      RNA binding factors acting on the p53 3'UTR.

PMID- 8861967
TI  - A long-range RNA-RNA interaction forms a pseudoknot required for translational
      control of the IF3-L35-L20 ribosomal protein operon in Escherichia coli.
AB  - In the IF3-L35-L20 operon encoding translation initiation factor 3 (IF3) and the
      two ribosomal proteins L35 and L20, the expression of the genes that code for the
      two ribosomal proteins is negatively regulated at the translational level by the
      cellular concentration of L20. This translational repressor directly regulates
      the expression of the gene encoding L35 and, via translational coupling, that of
      its own gene. Mutations that affect the control of the L35 gene were found
      exclusively at two sites: the first is located approximately 300 nucleotides
      upstream, and the second immediately 5' of the translation initiation site of the
      L35 gene. Mutations that fall between these two sites have little or no effect on
      the control, and the lack of effect of a deletion in the intervening region
      confirms this finding. RNA structure mapping in vitro suggests that the first
      site pairs with the second. We show that this pairing is also likely to occur in
      vivo because single mutations in either of these sites affect control, but base
      pair compensatory mutations re-establish control. We propose that these two
      distant sites can base-pair to form a long-range pseudoknot which is required for
      the control of the expression of the L35 gene.

PMID- 8861968
TI  - Dynamics of DNA-tracking by two sliding-clamp proteins.
AB  - Bacteriophage T4 gene 45 protein (gp45) and Escherichia coli beta are DNA
      tracking sliding-clamp proteins that increase processivity by tethering their
      conjugate DNA polymerases to DNA. gp45 also activates T4 late transcription. DNA
      loading of gp45 and beta requires ATP or dATP hydrolysis; efficient loading at
      primer-template junctions is assisted by single-stranded DNA-binding proteins.
      The kinetics of gp45 loading and tracking have been examined by DNase I
      footprinting of linear DNA with one blunt end, one primer-template junction, and
      binding sites for proteins that block gp45 tracking. DNA loading of gp45 can also
      be interrupted by adding the non-hydrolyzable ATP analog ATP-gamma-S. At
      saturation, DNA is very closely packed with gp45 or beta. When gp45 loading is
      interrupted, or when a segment of the track is blocked off, the gp45 footprint
      dissipates within seconds, but the DNA-tracking state of beta is much more
      stable. The stability of the tracking state of gp45 is, however, increased by the
      macromolecular crowding agent polyethylene glycol. We suggest that labile gp45
      catenation directly generates the coupling of late transcription to DNA
      replication during bacteriophage T4 multiplication.

PMID- 8861971
TI  - A piece of my mind. Touch me.

PMID- 8861972
TI  - FDA focuses on drug and device errors.

PMID- 8861969
TI  - A conserved domain of the large subunit of replication factor C binds PCNA and
      acts like a dominant negative inhibitor of DNA replication in mammalian cells.
AB  - Replication factor C (RF-C), a complex of five polypeptides, is essential for
      cell-free SV40 origin-dependent DNA replication and viability in yeast. The cDNA
      encoding the large subunit of human RF-C (RF-Cp145) was cloned in a Southwestern
      screen. Using deletion mutants of RF-Cp145 we have mapped the DNA binding domain
      of RF-Cp145 to amino acid residues 369-480. This domain is conserved among both
      prokaryotic DNA ligases and eukaryotic poly(ADP-ribose) polymerases and is absent
      in other subunits of RF-C. The PCNA binding domain maps to amino acid residues
      481-728 and is conserved in all five subunits of RF-C. The PCNA binding domain of
      RF-Cp145 inhibits several functions of RF-C, such as: (i) in vitro DNA
      replication of SV40 origin-containing DNA; (ii) RF-C-dependent loading of PCNA
      onto DNA; and (iii) RF-C-dependent DNA elongation. The PCNA binding domain of RF
      Cp145 localizes to the nucleus and inhibits DNA synthesis in transfected
      mammalian cells. In contrast, the DNA binding domain of RF-Cp145 does not inhibit
      DNA synthesis in vitro or in vivo. We therefore conclude that amino acid residues
      481-728 of human RF-Cp145 are critical and act as a dominant negative mutant of
      RF-C function in DNA replication in vivo.

PMID- 8861970
TI  - Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in
      deoxynucleotide binding and misinsertion fidelity of DNA synthesis.
AB  - Tyr115 is located in the vicinity of the polymerase catalytic site of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Site-directed
      mutagenesis was used to generate variant enzymes having Phe, Trp, Ala, Ser, Asp
      or Lys instead of Tyr115. The substitution of Tyr115 by Phe renders a fully
      active polymerase, displaying similar kinetic parameters, processivity and
      misinsertion fidelity of DNA synthesis as the wild-type enzyme. In contrast, the
      replacement of Tyr by Asp or Lys produced enzymes with a very low polymerase
      activity. The activity of the variant enzymes having Trp, Ala or Ser instead of
      Tyr115 was reduced significantly, particularly when poly(rA)484 was used as
      template. This effect was caused by a dramatic increase in the Km value for dTTP,
      and was detected using a DNA template mimicking a proviral HIV-1 gag sequence.
      Misinsertion fidelity assays revealed that mutants Y115W, Y115A and Y115S had a
      higher misinsertion efficiency than the wild-type reverse transcriptase. The low
      fidelity of these mutants appears to be related to nucleotide recognition rather
      than altered DNA-DNA template-primer interactions. The effects observed on the
      steady state kinetic constants, processivity and fidelity were mediated by the 66
      kDa subunit, as demonstrated using chimeric heterodimers with the Y115A
      substitution in either p66 or p51.

PMID- 8861974
TI  - 'Hands-on' center may offer a clue to health education in the 21st century.

PMID- 8861973
TI  - Questions raised about measles vaccine trial.

PMID- 8861975
TI  - Intensive smoking cessation efforts cost-effective.

PMID- 8861976
TI  - From the Centers for Disease Control and Prevention. Breast cancer incidence and
      mortality--United States, 1992.

PMID- 8861977
TI  - From the Centers for Disease Control and Prevention. Measles outbreak among
      school-aged children--Juneau, Alaska, 1996.

PMID- 8861978
TI  - Patient satisfaction with Medicaid managed care.

PMID- 8861979
TI  - Patient satisfaction with Medicaid managed care.

PMID- 8861980
TI  - Who benefits from medical savings accounts?

PMID- 8861981
TI  - Who benefits from medical savings accounts?

PMID- 8861982
TI  - Who benefits from medical savings accounts?

PMID- 8861983
TI  - Tobacco addiction.

PMID- 8861984
TI  - Perinatal transmission of HIV-1.

PMID- 8861985
TI  - Perinatal transmission of HIV-1.

PMID- 8861986
TI  - Initial choice of antidepressant therapy in primary care.

PMID- 8861987
TI  - Initial choice of antidepressant therapy in primary care.

PMID- 8861988
TI  - Predictors of type of vascular access in hemodialysis patients.
AB  - OBJECTIVE: Complications from vascular access account for 15% of hospital
      admissions among US hemodialysis patients. Complications are less frequent with
      arteriovenous fistulas than with synthetic grafts. We assessed clinical and
      nonclinical predictors of whether patients with end-stage renal disease (ESRD)
      starting hemodialysis receive a fistula or graft. We also investigated changes in
      practice between 1986-1987 and 1990. DESIGN: Cross-sectional study. SETTING:
      United States hemodialysis population. PATIENTS: Random, national samples of ESRD
      patients who started hemodialysis in 1986-1987 (n=2741) or 1990 (n=1409) from
      United States Renal Data System Special Studies. MAIN OUTCOME MEASURE: Type of
      permanent vascular access (arteriovenous fistula vs synthetic graft), analyzed
      using multivariate logistic regression. RESULTS: Clinical and demographic factors
      as well as socioeconomic status, region of residence, and year starting
      hemodialysis predicted the type of vascular access. Overall, 56% of patients had
      grafts 30 days after starting dialysis, but graft use increased from 51% in 1986
      1987 to 65% in 1990 (adjusted odds ratio [AOR], 1.67 for 1990 vs 1986-1987; 95%
      confidence interval [CI], 1.43-1.95; P<.001). Graft use (relative to fistula)
      varied by region of residence (ranging from AOR, 0.20; 95% CI, 0.14-0.28; P<.001
      [New England], to AOR, 2.69; 95% CI, 2.03-3.58; P<.001 [East South Central]; both
      relative to the national average). CONCLUSIONS: This national study documents
      large variations in the relative use of fistulas and grafts and a trend away from
      fistulas. The prevalence of comorbid conditions fails to explain these findings.
      Presentation and referral of patients early in the process of their ESRD,
      teaching surgeons to place fistulas, and training dialysis nurses to access
      fistulas may increase their use.

PMID- 8861989
TI  - Longitudinal screening for prostate cancer with prostate-specific antigen.
AB  - OBJECTIVE: To determine for the first 4 years of serial prostate-specific antigen
      (PSA)-based screening trends in compliance, prevalence of abnormal screening test
      results, cancer detection rates, and stage and grade of cancers detected. DESIGN:
      A community-based study of serial screening for prostate cancer with serum PSA
      measurements. SETTING: University medical center. SUBJECTS: A total of 10 248
      male volunteers at least 50 years old who were screened at 6-month intervals for
      a minimum of 48 months. MAIN OUTCOME MEASURES: The proportion of men who returned
      for serial screening, the proportion with elevated PSA levels, the proportion
      with newly elevated PSA levels, prostate cancer detection rates, and the
      distribution of tumor stages and grades at diagnosis. RESULTS: At 48 months, 79%
      of volunteers returned for screening. During this interval there was a decrease
      in the proportion of volunteers with serum PSA levels higher than 4.0 ng/mL (from
      10% to 6%-7%), in cancer detection rates (from 3% to <1%), and in the proportion
      with clinically advanced cancer (from 6% to 2%). In men who underwent surgery,
      the proportion with high-grade cancer decreased (from 11% to 6%), and the
      proportion with pathologically advanced cancer was proportionately reduced but
      not significantly reduced (from 33% to 27%). CONCLUSIONS: With serial PSA-based
      screening, the proportion of men with abnormal test results decreased, and the
      prostate cancer detection rate decreased to near the reported population-based
      incidence rate. There was also a shift to detection of cancers at an earlier
      clinical stage and detection of lower-grade cancers. If PSA screening is
      ultimately shown to be beneficial, then appropriate cost-benefit analyses will be
      required to determine how the shifts in cancer detection rate and cancer stage
      will affect the economics of serial PSA-based screening.

PMID- 8861990
TI  - Taking health status into account when setting capitation rates: a comparison of
      risk-adjustment methods.
AB  - OBJECTIVE: To compare performance of different health status measures for risk
      adjusting capitation rates. DESIGN: Cross-sectional study. Health status measures
      derived from 1 year were used to predict resources for that year and the next.
      SETTING: Group-network health maintenance organization in Minnesota.
      PARTICIPANTS: Sample of 18- to 64-year-old (n=3825) and elderly (aged > or = 65
      years; n=1955) members enrolled in a network-model health maintenance
      organization in Minnesota. MAIN OUTCOME MEASURES: Total expenditures in the year
      concurrent with the health status survey (July 1991 through June 1992) and total
      expenditures in the year following the survey (July 1992 through June 1993).
      RESULTS: Capitation adjustment based on demographic measures performed least
      well. Both self-reported health status measures and diagnoses predicted future
      expenditures twice as well as demographics. When predicting costs for groups of
      patients rather than individuals, the demographic model worked well for average
      groups but tended to overpredict healthier groups and underpredict sicker groups.
      Ambulatory Care Groups based on diagnoses performed better than self-reported
      health status both in the retrospective models and across healthier and sicker
      groups. CONCLUSIONS: Without risk adjustment, capitation rates are likely to
      overpay or underpay physicians for certain patient groups. It is possible to
      improve prediction using health status measures for risk adjustment. When
      selection bias is suspected and administrative data are available, we recommend a
      risk-adjustment method based on diagnostic information. If diagnostic data are
      not available, we recommend a system based on simple self-reported measures, such
      as chronic conditions, rather than complex functional status measures.

PMID- 8861991
TI  - Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent
      diabetes mellitus: a randomized clinical trial. Department of Veterans Affairs
      Implantable Insulin Pump Study Group.
AB  - OBJECTIVE: To determine whether implantable insulin pump (IIP) therapy and
      multiple daily insulin (MDI) injections could equally attain improved blood
      glucose control, and to compare the 2 treatments with respect to reducing daily
      blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and
      improving patients' quality of life. DESIGN: Randomized clinical trial. SETTING:
      Seven Veterans Affairs medical centers. PATIENTS: One hundred twenty-one male
      type II diabetic patients between the ages of 40 and 69 years, receiving at least
      1 injection of insulin per day and having hemoglobin A1c (HbA1c) levels of 8% or
      above. INTERVENTION: Intensive therapy (IIP or MDI) for 1 year. MAIN OUTCOME
      MEASURES: Hemoglobin A1c and blood glucose levels. RESULTS: Blood glucose levels
      declined to 7.96+/-1.08 mmol/L (143.4+/-19.5 mg/dL) and 8.30+/-1.52 mmol/L
      (149.6+/-27.4 mg/dL) (mean +/- SD) for IIP and MDI, respectively (P=.57).
      Hemoglobin A1c levels improved in both groups (time effect P<.001), to means of
      7.54%+/-0.83% (MDI) vs 7.34%+/-0.79% (IIP). IIP reduced blood glucose
      fluctuations compared with MDI (P<.001), and reduced the incidence of mild
      clinical hypoglycemia by 68% (P<.001); IIP also eliminated the weight gain
      associated with MDI therapy and yielded better overall quality-of-life (P=.03)
      and impact-of-disease subscale scores (P=.05). Adverse events included 25% of
      subjects with episodes of insulin underdelivery due to microprecipitates of
      insulin within the pump. CONCLUSIONS: Intensive insulin therapy with IIP and MDI
      is effective in controlling non-insulin-dependent diabetes mellitus. IIP has
      significant advantages in reducing glycemic variability, clinical hypoglycemia,
      and weight gain, while improving aspects of quality of life.

PMID- 8861992
TI  - Should a moratorium be placed on sublingual nifedipine capsules given for
      hypertensive emergencies and pseudoemergencies?
AB  - Over the past 2 decades, nifedipine in the form of capsules has become widely
      popular in the treatment of hypertensive emergencies. Unlike other agents, such
      as sodium nitroprusside, nicardipine hydrochloride, diazoxide, and nitroglycerin-
      which require intravenous administration and monitoring of blood pressure-
      nifedipine can be given orally, and close monitoring is said not to be necessary.
      Although administration of nifedipine capsules has been reported to be expedient
      and safe, it has not been approved by the Food and Drug Administration for
      labeling for treatment of hypertensive emergencies or of any other form of
      hypertension because of lack of outcome data. A review of the literature revealed
      reports of serious adverse effects such as cerebrovascular ischemia, stroke,
      numerous instances of severe hypotension, acute myocardial infarction, conduction
      disturbances, fetal distress, and death. Sublingual absorption of nifedipine has
      been found to be poor; most of the drug is absorbed by the intestinal mucosa.
      Given the seriousness of the reported adverse events and the lack of any clinical
      documentation attesting to a benefit, the use of nifedipine capsules for
      hypertensive emergencies and pseudoemergencies should be abandoned.

PMID- 8861993
TI  - Large trials vs meta-analysis of smaller trials: how do their results compare?
AB  - OBJECTIVE: To evaluate the results of large clinical trials vs the pooled results
      of smaller trials. DATA IDENTIFICATION: Meta-analyses with at least 1 "large"
      study were identified from the Cochrane Pregnancy and Childbirth Database and
      from MEDLINE (1966-1995). STUDY SELECTION: We used a sample size approach to
      select 79 meta-analyses with at least 1 large study of 1000 or more patients. We
      used a statistical power approach to select 61 meta-analyses with at least 1
      large study based on statistical power considerations. DATA EXTRACTION: The
      outcome of interest for each meta-analysis was the primary one stated in the
      original publication or, when not clearly specified, was decided on clinically.
      DATA SYNTHESIS: By random effects calculations, we found agreement between large
      and smaller trials in 90% of the meta-analyses selected by the sample size
      approach and in 82% of the meta-analyses selected by the statistical power
      approach. Twice as many disagreements appeared when the variability among large
      studies and among smaller studies was not considered (ie, fixed effects
      calculations). Of the 15 disagreements between results of large and smaller
      trials using the random effects model, plausible explanations were identified in
      10 meta-analyses: 5 with differences in the control rate of events between large
      and smaller trials, 4 with specific protocol or study differences, and 1 with
      potential publication bias. Two other disagreements were not clinically
      important, and tentative reasons could be identified for 2 of the remaining 3
      disagreements. CONCLUSIONS: Results of smaller studies are usually compatible
      with the results of large studies, but discrepancies do occur even when the
      diversity among both large studies and smaller studies is considered. Clinically
      important differences without a potential explanation are extremely uncommon.
      Future research should further examine sources of heterogeneity between the
      results of large and smaller trials.

PMID- 8861994
TI  - Recommendations for reporting cost-effectiveness analyses. Panel on Cost
      Effectiveness in Health and Medicine.
AB  - OBJECTIVE: This article, the third in a 3-part series, describes recommendations
      for the reporting of cost-effective analyses (CEAs) intended to improve the
      quality and accessibility of CEA reports. PARTICIPANTS: The Panel on Cost
      Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA,
      clinical medicine, ethics, and health outcomes measurement, convened by the US
      Public Health Service. EVIDENCE: The panel reviewed the theoretical foundations
      of CEA, current practices, alternative methods, published critiques of CEAs, and
      criticisms of general CEA methods and reporting practices. CONSENSUS PROCESS: The
      panel developed recommendations through 2 1/2 years of discussions. Comments on
      preliminary drafts were solicited from federal government methodologists, health
      agency officials, and academic methodologists. CONCLUSIONS: These recommendations
      are proposed to enhance the transparency of study methods, assist analysts in
      providing complete information, and facilitate the presentation of comparable
      cost-effectiveness results across studies. Adherence to reporting conventions and
      attention to providing information required to understand and interpret study
      results will improve the relevance and accessibility of CEAs.

PMID- 8861995
TI  - The FDA's decisions regarding new indications for approved drugs. Where's the
      evidence?

PMID- 8861996
TI  - Grafts vs fistulas for hemodialysis patients: equal access for all?

PMID- 8861997
TI  - Whatever happened to the health insurance crisis in the United States? Voices
      from a national survey.

PMID- 8861998
TI  - The position of the heterologous domain can influence the solubility and
      proteolysis of beta-galactosidase fusion proteins in E. coli.
AB  - The VP1 protein (23 kDa) of the foot-and-mouth disease virus has been produced in
      MC1061 and BL21 E. coli strains as beta-galactosidase fusion proteins, joined to
      either the amino and/or the carboxy termini of the bacterial enzyme. In BL21,
      devoid of La protease, all the recombinant fusion proteins are produced at higher
      yields than in MC1061, and occur mainly as inclusion bodies. The fusion of VP1 at
      the carboxy terminus yields a protease-sensitive protein whose degradation
      releases a stable, enzymatically active polypeptide indistinguishable from the
      native beta-galactosidase. On the contrary, when the same viral domain is fused
      to the amino terminus, the resulting chimeric protein is resistant to proteolysis
      even in the soluble form. These data demonstrate that the position of the
      heterologous domain in beta-galactosidase fusion proteins would not be irrelevant
      since it can dramatically influence properties of biotechnological interest such
      as solubility and proteolytic resistance.

PMID- 8861999
TI  - Optimization of the rate of DNA hybridization and rapid detection of methicillin
      resistant Staphylococcus aureus DNA using fluorescence polarization.
AB  - The hybridization rate of two complementary single-stranded DNA 24-mers was
      determined at various NaCl concentrations using a fluorescence polarization
      method. The rate was taken as the rate constant of the second order reaction,
      obtained by mathematical fitting of the time course curves of hybridization. The
      rate increased with the NaCl concentration, plateauing in the concentration range
      of about 1-2 M. Over the temperature range of 46 degrees C to 56 degrees C, it
      was found that in 0.8 M NaCl, hybridization was complete in under 10 min and that
      the difference in the polarization values between specific hybridization and non
      specific binding was greater at lower temperatures. Under the optimized
      conditions of 0.8 M NaCl at 46 degrees C, the time for DNA hybridization to reach
      90% completion decreased to less than 5 min. The assay time for one sample was 10
      min and the detection limit was of the order of 10(-10) M (40 fmol per assay).
      Under the optimized conditions, the DNA of methicillin resistant Staphylococcus
      aureus (MRSA), which had been multiplied by PCR, could be detected within 10 min.

PMID- 8862000
TI  - A specific chromophoric substrate for activity assays of 1,3-1,4-beta-D-glucan 4
      glucanohydrolases.
AB  - The synthesis of 4-methylumbelliferyl 3-beta-O-cellobiosyl-beta-D-glucopyranoside
      (3a) and its use as specific substrate to monitor enzyme activity of 1,3-1,4-beta
      D-glucan 4-glucanohydrolases are described. The chromophoric substrate 3a is
      prepared by a chemoenzymatic approach starting from barley grain, whose beta-D
      glucan polysaccharide is degraded down to a tri- and tetrasaccharide by an
      extracellular extract of recombinant E. coli expressing and secreting Bacillus
      licheniformis 1,3-1,4-beta-glucanase. The trisaccharide 1 is further chemically
      transformed into the title compound. Its use as substrate for an enzyme activity
      assay, the specificity of cleavage, and kinetic parameters are reported. As it
      undergoes a single glycosidic bond hydrolysis with release of 4
      methylumbelliferone, direct UV monitoring of the reaction provides a sensitive
      kinetic assay of the enzyme action.

PMID- 8862001
TI  - Integrated production of human insulin and its C-peptide.
AB  - The potential for the development of an integrated process for production of
      human insulin and its C-peptide in Escherichia coli has been investigated. Human
      proinsulin was produced intracellularly in E. coli fused to two synthetic IgG
      binding domains (ZZ) derived from staphylococcal protein A. High expression
      levels (3 g/l culture) of the gene product, which accumulated as inclusion
      bodies, was obtained. Solubilization of inclusion bodies by oxidative
      sulfitolysis and subsequent renaturation was performed directly after cell lysis
      and pellet wash. IgG affinity chromatography was used for efficient recovery of
      pure proinsulin fusion protein in a single step. Monomers of the proinsulin
      fusion protein constituted approximately 70%. A single step conversion of the
      fusion protein into insulin and C-peptide by trypsin and carboxypeptidase B
      treatment was achieved by engineering the junction between proinsulin and its
      affinity handle, ZZ. Characterization of the cleavage products by reversed phase
      chromatography (RPC) verified that human insulin and C-peptide were generated and
      that the ZZ affinity handle was resistant to cleavage. Human insulin and C
      peptide were recovered with high yields by preparative reversed-phase high
      performance liquid chromatography (RP-HPLC). The potential use of the presented
      scheme for large-scale production of recombinant insulin and/or its C-peptide is
      discussed.

PMID- 8862002
TI  - Production of cadmium sulphide microcrystallites in batch cultivation by
      Schizosaccharomyces pombe.
AB  - Cadmium sulphate was added to separate batch cultures of Schizosaccharomyces
      pombe during different growth phases to determine the effect on cadmium sulphide
      microcrystallite production. Exit gas analysis was used to determine the impact
      on metabolism. Addition during the early-exponential growth phase resulted in an
      immediate intracellular uptake of cadmium, followed by rapid efflux from the
      cells, permanent reduction in cell metabolism and a lower intracellular inorganic
      sulphide content. This response was not suitable for cadmium sulphide
      microcrystallite production. Stationary phase cultures did not induce cadmium
      sulphide microcrystallite production. However, the addition of cadmium sulphate
      to a culture during the mid-exponential growth phase increased the intracellular
      cadmium and inorganic sulphide concentrations for approximately 8 h before
      reaching a saturation level for the cell. This resulted in a significant level of
      cadmium sulphide microcrystallite production.

PMID- 8862003
TI  - Unanswered questions about multidrug resistance.

PMID- 8862004
TI  - Multidrug resistance evaluation by confocal microscopy in primary urothelial
      cancer explant colonies.
AB  - Assessing functional multidrug resistance (MDR) status in clinical biopsy
      material using drug autofluorescence has potential applications to clinical
      management. The small size of many cystoscopy specimens has led us to develop, as
      an alternative to flow cytometry, a protocol for studying epirubicin accumulation
      in adherent colonies of primary bladder cancer cells viewed live and in situ by
      confocal microscopy. The limitations to quantitation inherent in this technique
      are compensated for by preservation of cellular organisation and the elimination
      of non-malignant cells. Biopsy material is disaggregated and explanted into
      culture-grade petri dishes. After incubation for three to seven days plaques of
      epithelial cells have developed. Classical patterns of sensitive and resistant
      drug distribution are observed. Cells of the rolled edges of the colony
      accumulate more drug than those of the inner epithelial monolayer. Some central
      areas of larger colonies give the appearance of drug arrested at the
      intercellular junctions to give a fenestrated pattern. These observations
      contribute to the understanding of mechanisms in MDR as well as forming the basis
      for a clinical urological MDR evaluation protocol.

PMID- 8862005
TI  - Transporter molecules in multidrug resistance.

PMID- 8862006
TI  - Relationship of LRP-human major vault protein to in vitro and clinical resistance
      to anticancer drugs.
AB  - Multidrug resistance (MDR) has been related to two members of the ABC-superfamily
      of transporters, P-glycoprotein (Pgp) and Multidrug Resistance-associated Protein
      (MRP). We have described a 110 kD protein termed the Lung Resistance-related
      Protein (LRP) that is overexpressed in several non-Pgp MDR cells lines of
      different histogenetic origin. Reversal of MDR parallels a decrease in LRP
      expression. In a panel of 61 cancer cell lines which have not been subjected to
      laboratory drug selection, LRP was a superior predictor for in vitro resistance
      to MDR-related drugs when compared to Pgp and MRP, and LRP's predictive value
      extended to MDR unrelated drugs, such as platinum compounds. LRP is widely
      distributed in clinical cancer specimens, but the frequency of LRP expression
      inversely correlates with the known chemosensitivity of different tumour types.
      Furthermore, LRP expression at diagnosis has been shown to be a strong and
      independent prognostic factor for response to chemotherapy and outcome in acute
      myeloid leukemia and ovarian carcinoma (platinum-based treatment) patients.
      Recently, LRP has been identified as the human major protein. Vaults are novel
      cellular organelles broadly distributed and highly conserved among diverse
      eukaryotic cells, suggesting that they play a role in fundamental cell processes.
      Vaults localise to nuclear pore complexes and may be the central plug of the
      nuclear pore complexes. Vaults structure and localisation support a transport
      function for this particle which could involve a variety of substrates. Vaults
      may therefore play a role in drug resistance by regulating the nucleocytoplasmic
      transport of drugs.

PMID- 8862007
TI  - mdr1 ribozyme mediated reversal of the multi-drug resistant phenotype in human
      lung cell lines.
AB  - An mdr1 hammerhead was introduced into two adriamycin-selected multi-drug
      resistant human lung cell lines both of which over-express p-glycoprotein.
      Expression of the ribozyme resulted in a decrease in mdr1 mRNA expression and an
      increase in drug sensitivity in both cell lines. This would suggest that the use
      of specific ribozymes may represent an effective and specific approach in order
      to restore cellular sensitivity towards anti-cancer drugs.

PMID- 8862008
TI  - Overexpression of P-glycoprotein in heat- and/or drug-resistant hepatoma
      variants.
AB  - We have earlier isolated a glucocorticoid-resistant, dedifferentiated rat
      hepatoma variant, the clone 2, which exhibited deficient stress activation of the
      major stress-inducible heat-shock protein hsp68. Multidrug-resistant variants
      were isolated from clone 2 cells using increasing concentrations of colchicine.
      The induction deficiency of hsp68 was maintained in the colchicine-resistant
      clone 2 cells grown for several months in the presence of 1 microgram/ml
      colchicine (termed as highly multidrug-resistant variant) indicating that this
      heat-shock protein is not involved in the multidrug resistance. No alteration of
      the protein synthesis pattern was observed except the strong increase of the P
      glycoprotein, which correlated with high level of corresponding mRNA. Stable heat
      resistant variants of clone 2 were also isolated, which showed increased drug
      resistance to several drugs, i.e. they became moderately multidrug-resistant.
      This moderate multidrug resistance of the heat-resistant variants was further
      increased by stepwise selection with colchicine (highly multidrug-resistant heat
      resistant variants). The levels of P-glycoprotein mRNA and protein were elevated
      both in the heat-resistant, non drug selected, moderately drug-resistant and in
      heat-resistant, colchicine selected, highly drug-resistant variants. Decreased
      retention of antitumor drugs was observed in all multidrug-resistant variants
      indicating that P-glycoprotein was functional. Verapamil increased doxorubicin
      retention and cytotoxicity significantly. Our results showing that severely
      stressed hepatoma cells overexpressed the multidrug resistance gene(s) raise the
      possibility that the P-glycoprotein may participate in protection against
      environmental stress such as heat.

PMID- 8862009
TI  - Alternating bolus and continuous infusion 5-fluorouracil: a strategy to overcome
      resistance to this fluoropyrimidine in advanced colorectal cancer patients.
AB  - Focusing our effort on the importance of FUra scheduling we have tested the
      hypothesis that pulse and continuous infusion (CI) of the fluoropyrimidine have
      different mechanisms of cytotoxicity. Our initial approach was to compare the
      mechanism of resistance of a cell line resistant to a short term exposure to FUra
      (HCT-8/FU4hR) to that of a cell line resistant to a prolonged exposure to the
      fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed that HCT-8/FU4hR
      cells were still sensitive to FUra given as a 7-d exposure, suggesting different
      mechanisms of resistance. Indeed, rapid recovery of TS activity after drug
      removal was evident in the HTC-8/FU7dR cell line while HCT-8/FU4hR cells were
      similar to the parental cell line with regard to both the degree of in situ TS
      inhibition by FUra and duration of inhibition after FUra removal. In contrast,
      labelling studies with [3H-6]FUra(4 h exposure, 100 microM) showed that the
      incorporation of the fluoropyrimidine into RNA is significantly decreased in HCT
      8/FU4hR cells as compared to parental HCT-8 cells. Given the lack of cross
      resistance between the two schedules in vitro, a pilot trial was done on patients
      with colorectal cancer refractory to bolus FUra. On 15 patients failing after
      FUra+LV or FUra alone 1 PR, 3 MR, 3 SD and 8 P were observed, confirming a
      certain degree of activity of CI FUra in patients clinically resistant to bolus
      FUra. Based on this rationale, a phase II trial of schedule-oriented biochemical
      modulation of FUra in advanced colorectal cancer patients was conducted,
      employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600 mg/sqm),
      preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the
      RNA effect of the drug) alternating with Fura continuous infusion, 200 mg/sqm
      daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to
      maximize the DNA effect). Thirty-three consecutive patients (median ECOG PS 1)
      with advanced measurable colorectal cancer and no prior therapy for metastatic
      disease entered the study, from February 1992 to August 1993. Three complete and
      13 partial responses were obtained among these 33 patients (RR = 48%, 95%
      confidence limits, 31-66%). After a median follow-up time of 23 months, 16
      patients are still alive. The median progression free survival and overall
      survival were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4
      toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle
      was: mucositis 6%, diarrhea 3% and vomiting 3% for the bolus part and 21%, 3% and
      6% respectively, for the continuous infusion part of the regimen. Hand-foot
      syndrome occurred in 27% of the patients treated with the continuous infusion
      regimen. In conclusion, this experimental and clinical project has generated a
      novel regimen of schedule oriented biochemical modulation that is twice as active
      and half as toxic compared to bolus FU+LV given with either the daily x 5 or the
      weekly schedule. This high clinical activity is very encouraging, especially
      considering that 1) consecutive patients were entered, 2) the responses were
      independently reviewed, 3) the progression free survival and survival were much
      longer than those actually reported for this disease, 4) the toxicity of the
      program, in particular the bolus regimen, was relatively low allowing further
      intensification.

PMID- 8862010
TI  - Induction of MRP/GS-X pump and cellular resistance to anticancer prostaglandins.
AB  - We provide evidence that the expression of the human MRP/GS-X pump encoded by the
      MRP (multidrug resistance associated protein) gene is induced by cisplatin in
      human leukemia HL-60/R-CP (cisplatin-resistant) cells and modulates cell growth
      inhibition by delta(7)-prostaglandin A1 (PGA1) methyl ester. The MRP mRNA level
      in HL-60/R-CP cells increased remarkably after a 24-h incubation with 20 microM
      cisplatin; interestingly, however, no amplification of the MRP gene was detected.
      In cisplatin-sensitive HL-60 cells, which express the MRP/GS-X pump at low
      levels, c-myc expression was substantially suppressed by delta(7)-PGA1 methyl
      ester and the cell cycle was arrested in G1 phase. By contrast, in HL-60/R-CP
      cells overexpressing the MRP/GS-X pump, c-myc expression and cell proliferation
      were much less affected by delta(7)-PGA1 methyl ester. This suggests that
      induction of the MRP/GS-X pump may confer on cancer cells resistance to
      anticancer prostaglandins and that the resistance mechanism may involve the
      increased efflux of PG-glutathione conjugates, as active intermediates, from the
      cells via the MRP/GS-X pump.

PMID- 8862011
TI  - Anthracycline drugs and MDR expression in human leukemia.
AB  - We investigated the expression of P-glycoprotein (P-gp) in 50 adults with de novo
      acute myeloid leukemia (AML) at the initial diagnosis in order to further define
      the relationship between the presence of P-gp on leukemic cells and the efficacy
      of two different anthracycline drugs, Daunorubicin (DNR) and Idarubicin (IRR), in
      terms of remission, induction and survival. We found that 30 (60%) of the 50
      patients were negative for P-gp expression (group 1) and 20 patients (40%) were
      positive (group 2) for P-gp expression by MRK16MoAb using a cut of 10% positive
      cells. Among the 50 patients, 35 (70%) obtained complete remission (CR);
      depending on P-gp expression the CR rate was 80% for group 1 and 45% for group 2
      (p < 0.005). The median duration of overall survival (OS) was 20 months for
      patients in group 1, compared to 10 months for patients in group 2 (p < 0.005).
      Regarding the anthracycline used, no difference in CR has been observed in
      patients of group 1 (75% CTR with DNR versus 90% CR with IDR); on the contrary in
      group 2 we observed 40% CR with DNR versus 70% CR with IDR (p < 0.005). No
      significant difference has been achieved in group 1 terms of median duration of
      overall survival between DNR and IDR regimen; on the contrary the median duration
      of OS in patients of group 2 treated with IDR regimen was significantly longer
      than DNR regimen (p < 0.005). These results confirm the prognostic value of P-gp
      expression in AML at diagnosis and we suggest that Idarubicin could be a valid
      anthracycline drug for reversing multidrug resistance.

PMID- 8862012
TI  - Absence of correlation between chemo- and radioresistance in a range of human
      tumour cell lines.
AB  - The correlation between cellular resistance to radiation and to chemotherapeutic
      drugs has been investigated in a number of solid tumour cell lines, and
      preliminary results indicate no direct relationship. The acquisition of a
      multidrug resistance (MDR) profile by adriamycin-selected variants of a human
      squamous lung carcinoma, an ovarian carcinoma, a cervical carcinoma and by a
      colchicine-selected variant of a Chinese hamster ovarian carcinoma resulted in
      alterations to their radiosensitivity. However, the degree of change in the
      radiosensitivity of the MDR cell lines could not be predicted from their level of
      resistance to adriamycin. Clonal populations derived from DLKP-A, an adriamycin
      selected MDR variant of the human lung carcinoma cell line DLKP, exhibited
      individual radiosensitivity profiles, which did not correlate with their
      chemoresistance. Exposure of DLKP to consecutive increasing doses of radiation
      did not confer cross-resistance to chemotherapeutic drugs.

PMID- 8862013
TI  - Decreased in vitro chemosensitivity of tumour cells in patients suffering from
      malignant diseases with poor prognosis.
AB  - The aim of the study was to assess the predictive value of MTT in vitro assay for
      evaluation of tumour cell resistance/sensitivity to cytotoxic drugs. We analyzed
      105 samples of malignant cells of different origin. The study included patients
      with a diagnosis of acute and chronic lymphatic leukaemia, acute and chronic
      myeloid leukaemia, non-Hodgkin lymphoma, carcinoma of the lung, stomach and
      liver, rhabdomyosarcoma and breast carcinoma. The results demonstrate outstanding
      chemosensitivity in the majority of childhood acute lymphoblastic leukaemias,
      medium chemosensitivity of adult haematopoietic malignant diseases and
      chemoresistance of solid tumour cells. Our preliminary data suggest a good
      correlation between in vitro MTT assay and clinical curability of individual
      malignant diseases.

PMID- 8862014
TI  - Topology of MDR1-P-glycoprotein as indicated by epitope mapping of monoclonal
      antibodies to human MDR cells.
AB  - The MDR1-P-glycoprotein binding sites of three different murine monoclonal
      antibodies (MM4.17, MM6.15 and MC57), directed towards living, intact human
      multidrug-resistant cells were investigated in order to study P-glycoprotein
      topology. By using synthetic peptide scanning, we demonstrated that well-defined
      regions localized on the predicted first, fourth and sixth extracellular loops
      are external. On the basis of the structure of MM6.15 epitope, which is
      distributed on the above three different extracellular loops (and thus is
      discontinuous), P-glycoprotein molecules result to be differently organized in
      the lipid bilayer. Moreover, the outcome of the MC57 and MM4.17 epitopes
      localization experiments, obtained through the use of phage-displayed peptide
      libraries, represent an additional challenge to the classical 12-transmembrane
      domain model of P-glycoprotein, since they agree with the novel topography of the
      molecule (10-transmembrane domain), which was recently proposed on the basis of
      biochemical and expression studies.

PMID- 8862016
TI  - Hydration of oleic acid by a Selenomonas strain from the ovine rumen.
AB  - A Selenomonas sp., isolated from the ovine rumen, was characterized with regard
      to its ability to hydrate oleic acid to 10-hydroxystearic acid. Hydration
      occurred only in stationary phase in a medium containing 0.1%, 0.5% (w/v)
      galactose or 0.5% (w/v) glucose, but not in a medium containing 1% galactose.
      Growth under a hydrogen headspace did not result in the production of stearic
      acid, the biohydrogenated product of oleic acid. Linoleic and linolenic acids
      (0.1% v/v) were not hydrated. It is concluded that the growing bacterium is
      unlikely to contribute to oleic acid hydration in the rumen.

PMID- 8862015
TI  - Evaluation of P-glycoprotein expression in soft tissue sarcomas of the
      extremities.
AB  - Soft tissue sarcomas comprise a heterogeneous group of mesenchymal tumors
      accounting for less than one-percent of adult neoplasms. In the last few years,
      the use of adjuvant chemotherapy has been proposed for the treatment of these
      lesions in order to obtain a better systemic control, but its usefulness is still
      controversial. In this study, we evaluated whether P-glycoprotein, a membrane
      protein strictly associated with multidrug resistance, is overexpressed in soft
      tissue sarcomas. By using human multidrug resistant sarcoma cell lines as
      controls, we analyzed P-glycoprotein expression in 34 primary and in 23 relapsed
      soft tissue sarcomas of the extremities. Overexpression of P-glycoprotein was
      found in 6 out of 34 primaries (18%) and in 8 out of 23 relapses (35%). In
      particular, in malignant fibrous histiocytoma, the most frequent soft tissue
      sarcoma of adults, P-glycoprotein overexpression was found in 23% of primary
      untreated cases, in agreement with the reported relapse rate of this tumor after
      surgery and chemotherapy. These data suggest that, in soft tissue sarcomas,
      overexpression of P-glycoprotein may be of prognostic value and that the
      assessment of P-glycoprotein expression may be useful for the design of
      chemotherapy protocols.

PMID- 8862017
TI  - Inactivation of bacteria and yeasts on agar surfaces with high power Nd:YAG laser
      light.
AB  - Near infrared light from a high-powered, 1064 nm, Neodymium:Yttrium Aluminium
      Garnet (Nd:YAG) laser killed a variety of Gram-positive and Gram-negative
      bacteria and two yeasts, lawned on nutrient agar plates. A beam (cross-sectional
      area, 1.65 cm2) of laser light was delivered in 10 J, 8 ms pulses at 10 Hz, in a
      series of exposure times. For each microbial species, a dose/response curve was
      obtained of area of inactivation vs energy density (J cm-2). The energy density
      that gave an inactivation area (IA) equal to 50% of the beam area was designated
      the IA50-value and was plotted together with its 95% confidence limits. Average
      IA50-values were all within a threefold range and varied from 1768 J cm-2 for
      Serratia marcescens to 4489 J cm-2 for vegetative cells of Bacillus
      stearothermophilus. There were no systematic differences in sensitivity
      attributable to cell shape, size, pigmentation or Gram reaction. At the lowest
      energy densities where inactivation was achieved for the majority of organisms
      (around 2000 J cm-2), no effect was observed on the nutrient agar surface, but as
      the energy density was increased, a depression in the agar surface was formed,
      followed by localized melting of the agar.

PMID- 8862018
TI  - Enterotoxin-producing strains of Bacillus thuringiensis isolated from food.
AB  - Strains of Bacillus thuringiensis were isolated from various food items (pasta,
      pitta bread and milk) and were found to belong to either H-serotype kurstaki or
      neoleonensis. The strains were bioassayed against Pieris brassicae and
      insecticidal activity of strains was found to correspond to the presence of the
      cry1A-gene. All strains, except one, were found to express cytotoxic effects on
      Vero cells as an indicator of enterotoxin activity. Further, the B. thuringiensis
      strains HD-1 (serotype kurstaki), NB-125 (serotype tenebrionis) and HD-567
      (serotype israelensis ) which are used commercially for insect pest management,
      were also found to have cytotoxic effects on Vero cells.

PMID- 8862019
TI  - Growth inhibition of a human oral bacterium Porphyromonas gingivalis by rat
      cysteine proteinase inhibitor cystatin S.
AB  - Agar diffusion analysis demonstrated that rat cystatin S, a cysteine proteinase
      inhibitor, inhibited the growth of all tested strains of a human oral, Gram
      negative anaerobic periodontopathogen Porphyromonas gingivalis. Its specific
      inhibitory activity against this tissue-invasive bacterium but not against other
      tested oral bacterial species emphasized the importance of specific cysteine
      proteinases for growth of P. gingivalis.

PMID- 8862020
TI  - Potential chitinase activating factor from yeast cells of Candida albicans.
AB  - Microsomal chitinase from yeast and hyphal cells of Candida albicans was
      activated endogenously by incubation at 30 degrees C and exogenously by trypsin.
      The putative activating factor of yeast cells was separated from chitinase
      activity by fractionation of lysed protoplasts on an Iodixanol density gradient.
      The vacuole fraction contained no significant chitinase activity, but was
      enriched in chitinase activating factor. Activity of microsomal chitinase
      increased upon incubation with this, but no other gradient factor. Results
      suggest that the regulatory system governing microsomal chitinase activity, like
      that governing chitin synthase, involves a 'vacuolar' activating factor in
      Candida albicans.

PMID- 8862021
TI  - PCR-RFLP analysis of the large subunit (23S) ribosomal RNA genes of Campylobacter
      jejuni.
AB  - Forty-seven strains of Campylobacter jejuni were examined by PCR-RFLP analysis of
      23S rRNA genes. Seven different molecular profiles were detected by a combination
      of HpaII AluI and DdeI digest analysis. Most (83%) strains, including those with
      different Penner serotypes and from different hosts, had the same molecular
      profiles. The high level of conservation apparent within the 23S rDNA sequences
      confirmed their value as targets in species-specific PCR identification assays
      but not for subtypic discrimination within Camp. jejuni.

PMID- 8862022
TI  - Sub-typing of animal and human Campylobacter spp. using RAPD.
AB  - Based on a 10-mer primer (5'-CCTGTTAGCC-3'), a random amplified polymorphic DNA
      (RAPD) method for typing Campylobacter coli isolated from pigs was developed. The
      method proved effective with a high discrimination and good reproducibility. In
      contrast with serotyping no untypable strains were found out of a total of 269
      isolates (veterinary, food and clinical) examined. The method was also
      successfully applied to typing Campylobacter jejuni from a similar range of
      sources.

PMID- 8862023
TI  - Effect of fungistatic agent 2-deoxy-D-glucose on mycotoxins from Penicillium
      expansum.
AB  - Mycotoxin production from Penicillium expansum was effected by the 'biocontrol
      enhancer' 2-deoxy-D-glucose (DOG). Citrinin and gentisyl alcohol were produced in
      higher amounts, whereas patulin was inhibited, which represents a differential
      effect on the polyketide metabolic pathway. These effects have implications for
      the use of DOG in biocontrol.

PMID- 8862024
TI  - Detection of Escherichia coli O157:H7 in water from coliform enrichment cultures.
AB  - Environmental water samples were seeded with Escherichia coli O157:H7 and the
      bacterium was recovered using a traditional coliform enrichment procedure
      followed by selective plating on sorbitol MacConkey agar and biochemical and
      serological characterization. Assays for beta-glucuronidase and glutamate
      decarboxylase were found to be useful procedures for screening suspected
      isolates. The organism was not recovered in a survey of various water samples.

PMID- 8862025
TI  - Thermal resistance of Bacillus stearothermophilus spores in different heating
      systems containing some approved food additives.
AB  - The effects of different heating systems on the heat resistance of Bacillus
      stearothermophilus spores (ATCC 7953, 12980, 15951 and 15952) were investigated.
      Spores were heated in distilled water, Sorensen buffer (0.18 mol 1-1), McIlvaine
      buffer (0.0025-0.18 mol 1-1), and several solutions containing sodium chloride
      (0.06-12%), sodium nitrite (125 ppm), potassium sorbate (0.1%) and sodium
      benzoate (0.1%) over a wide range of temperatures (115-140 degrees C). D-values
      obtained for McIlvaine and Sorensen buffers, at the same molarities, were not
      significantly different (P > 0.05), but decimal reduction times increased as
      phosphate concentrations in the solutions decreased. The concentrations, in which
      statistically significant differences (P < 0.05) were obtained, varied among
      strains. Among the additives assayed, only sodium chloride reduced heat
      resistance, being effective at concentrations as low as 0.06%. The z-values
      calculated in this study ranged from 6.99 to 8.40 with a mean value of 7.60 +/-
      0.45. Although z-values observed for salt and buffers (180 mol 1-1) were slightly
      higher than obtained in the other conditions assayed, the difference was not
      statistically significant (P > 0.05).

PMID- 8862026
TI  - The isolation and characterization of a rumen chitinolytic bacterium.
AB  - Chitinolytic bacteria were detected in faeces and digesta of wild and
      domesticated herbivores. The presence of chitinolytic bacteria in two cows was
      verified following enrichment culture of rumen fluid on colloidal chitin. In
      three other cows, direct counts on chitin agar showed that the numbers of these
      bacteria in the rumen fluid ranged from 5 x 10(4) to 2 x 10(8) ml-1. Most of
      these bacteria were Clostridium-like spore producers. The most typical strain,
      Clostridium sp. ChK5, was characterized further. This bacterium degraded
      colloidal chitin and produced mainly acetate, butyrate and lactate. Endochitinase
      and chitobiase were produced when chitin was the growth substrate. Endochitinase
      was also detected in cultures grown on N-acetylglucosamine and glucose. Optimal
      conditions for endochitinase activity were 37 degrees C and pH 4.5-6.1. The
      Michaelis constant (Km) for this enzyme was 19.3 mg ml-1. Strain ChK5 shows
      strong phenotypic similarity to Clostridium tertium.

PMID- 8862027
TI  - The effect of rumen chitinolytic bacteria on cellulolytic anaerobic fungi.
AB  - The polycentric anaerobic fungus Orpinomyces joyonii A4 was cultivated on
      microcrystalline cellulose alone and in association with the rumen chitinolytic
      bacterium Clostridium sp. strain ChK5, which shows strong phenotypic similarity
      to Clostridium tertium. The presence of strain ChK5 significantly depressed the
      solubilization of microcrystalline cellulose, the production of short-chain fatty
      acids (SCFA) and the release of endoglucanase by the fungus. Co-culture of the
      monocentric anaerobic fungus Neocallimastix frontalis strain RE1, Neocallimastix
      sp. strain G-1 and Caecomyces sp. strain SC2 with strain ChK5 also resulted in
      depressed fungal cellulolysis. Cell-free supernatant fluids from strain ChK5
      inhibited the release of reducing sugars from carboxymethylcellulose by cell-free
      supernatant fluids from O. joyonii strain A4. Strain 007 of the cellulolytic
      anaerobe Ruminococcus flavefaciens was also shown to produce small amounts of
      soluble products upon incubation with colloidal chitin. Mixtures of culture
      supernates from this bacterium and from O. joyonii strain A4 showed cellulase
      activity that was less than that of the component cultures. It is suggested that
      the ability of some rumen bacteria to hydrolyse or transform chitin may be an
      important factor in the interactions between bacteria and fungi in the rumen.

PMID- 8862028
TI  - Complete amino acid sequences of two trypsin inhibitors from buckwheat seed.
AB  - The major trypsin isoinhibitors from seed extracts of buckwheat (Fagopyrum
      esculentum Monch) were purified by affinity chromatography, anion exchange
      chromatography, anion exchange HPLC and reversed-phase HPLC, and the complete
      amino acid sequences of two isoinhibitors, BTI-1 and BTI-2, were established by
      automated Edman degradation. Each isoinhibitor consists of a single polypeptide
      chain of 69 amino acids, including two Cys residues. The N-terminal sequence of a
      third isoform, BTI-3, was also determined. The buckwheat trypsin isoinhibitors
      exhibit clear sequence similarities with the potato chymotrypsin inhibitor I
      family of serine proteinase inhibitors.

PMID- 8862029
TI  - Differential inhibition of eukaryote protein kinases by condensed tannins.
AB  - Condensed tannins, isolated from a variety of plant sources, were characterized
      according to the constituent flavans, being based on procyanidin and/or
      prodelphinidin and having a cis or trans stereochemistry at positions 2 and 3.
      All the tannin preparations are potent inhibitors of rat liver cyclic AMP
      dependent protein kinase catalytic subunit (cAK) with IC50 values (concentrations
      for 50% inhibition) ranging from 0.009 to 0.2 microM. The tannin preparations are
      very good inhibitors of rat brain Ca(2+)- and phospholipid-dependent protein
      kinase C (PKC) (IC50 values in the range 0.3-7 microM), wheat embryo Ca(2+)
      dependent protein kinase (CDPK) (IC50 values in the range 0.8-7 microM) and of
      calmodulin (CaM)-dependent myosin light chain kinase (MLCK) (IC50 values in the
      range 7-24 microM). One of the most effective preparations, that from the leaves
      of Ribes nigrum, has IC50 values with respect to cAK, PKC, CDPK and MLCK of
      0.009, 0.6, 2.0 and 16 microM, respectively. In general, the order with respect
      to sensitivity to inhibition by these condensed tannins is cAK > PKC > CDPK >
      MLCK. The Ribes nigrum preparation is a competitive inhibitor of cAK with respect
      to both ATP and synthetic peptide substrate. These condensed tannin preparations
      are the most potent plant-derived inhibitors of cAK yet found.

PMID- 8862030
TI  - Dermatolactone, a cytotoxic fungal sesquiterpene with a novel skeleton.
AB  - The nematicidal 5-pentyl-2-furaldehyde and the cytotoxic sesquiterpene
      dermatolactone were isolated from the extracts of an Ascomycete belonging to the
      Dermateaceae. The furan has previously been reported from the Basidiomycete Irpex
      lacteus, while dermatolactone is a new compound the structure of which was
      determined by spectrosocpic methods.

PMID- 8862031
TI  - Colutequinone and colutehydroquinone, antifungal isoflavonoids from Colutea
      arborescens.
AB  - Two new isoflavonoids have been isolated from the root bark of Colutea
      arborescens and identified as 7,3',4'-trimethoxyisoflavan-2',5'-quinone ((3R)
      colutequinone) and the corresponding hydroquinone (2',5'-dihydroxy-7,3',4'-tri
      methoxyisoflavan) ((3R)-colutehydroquinone).

PMID- 8862032
TI  - Two new bioactive diterpenes from Lepista sordida.
AB  - In a screening for inducers of the differentiation of human leukaemic cells, two
      new active diterpenoids were isolated from fermentations of the basidiomycete
      Lepista sordida. The structural elucidation by spectroscopic methods and the
      biological activities of both metabolites are described.

PMID- 8862033
TI  - A lignan and four terpenoids from Brucea javanica that induce differentiation
      with cultured HL-60 promyelocytic leukemia cells.
AB  - A novel lignan, guaiacylglycerol-beta-O-6'-(2-methoxy)cinnamyl alcohol either,
      three known simaroubolides, brusatol, dehydrobrusatol, yadanziolide C, and the
      known terpenoid, blumenol A, were obtained as active compounds from an ethyl
      acetate-soluble extract of Brucea javanica, using a bioassay based on the
      induction of cell differentiation with human promyelocytic leukemia (HL-60)
      cells. Also obtained were the known coumarinolignan, cleomiscosin A, and the
      known quassinoid glycoside, bruceoside B, which were inactive in the HL-60 cell
      test system. The structure of the new lignan was determined by a combination of
      1D and 2D NMR techniques.

PMID- 8862034
TI  - A water-soluble beta-D-glucan from Boletus erythropus.
AB  - The main component of a water extract of Boletus erythropus fruiting bodies is a
      M(r) 10(6) glucan. The use of classical structural analysis and HMQC
      (heteronuclear multiple quantum coherence) NMR experiments indicates a (1-->3)
      linked beta-D-glucan structure with a single glucose residue attached to O-6 of
      the main chain and a branching frequency of 1/3.

PMID- 8862035
TI  - Sesquiterpene O-naphthoquinones from the root bark of Ulmus davidiana.
AB  - Three new sesquiterpene ortho-naphthoquinones, davidianones A, B and C, together
      with four known compounds, mansonones E, F, H and I, were isolated from the root
      bark of Ulmus davidiana. On the basis of spectral data including pulse field
      gradient two-dimensional NMR spectroscopy, the structures of new compounds were
      established as 3-hydroxymethyl-6,9-dimethylnaphtho(1,8-b,c)pyran-7,8-dione, 6
      methoxycarbonyl-3,9-dimethylnaphtho(1,8-b,c)pyran-7,8-dione, 6-dimethoxymethyl
      3,9-dimethylnaphtho(1.8-b,c)pyran-7,8-d ion e, respectively. Their antioxidative
      activities were evaluated by a thiobarbituric acid method using rat liver
      microsomes, with mansonone F showing the greatest activity.

PMID- 8862036
TI  - Triterpenoid glycosides from Ilex kudincha.
AB  - Three new saponins, named kudinosides A, B and C, were isolated from the leaves
      of Ilex kudincha. On the basis of spectroscopic analysis and chemical
      transformation their structures were elucidated as 3-O-beta-D-glucopyranosyl-(1-
      >3)-[alpha-L-rhamnopyranosyl- (1-->2)]-alpha-L-arabinopyranosyl-beta
      kudinlactone, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->3)
      alpha-L- arabinopyranosyl-beta-kudinlactone and 3-O-beta-D-glucopyranosyl-(1-->2)
      beta-D-glucopyranosyl-(1-->3)-[alpha-L -rhamnopyranosyl-(1-->2)]-alpha-L
      arabinopyranosyl-beta-kudinla c tone.

PMID- 8862037
TI  - Bacopasaponin D--a pseudojujubogenin glycoside from Bacopa monniera.
AB  - A new dammarane-type pseudojujubogenin glycoside, bacopasaponin D, has been
      isolated from the reputed Indian medicinal plant Bacopa monniera and defined as 3
      O-[alpha-L-arabinofuranosyl(I-->2)beta-D-glucopyranosyl]pseudojujub ogenin by
      spectroscopic methods and some chemical transformations. The 13C signals of the
      saponin were assigned by DEPT, 1H-1H COSY and HSQC techniques.

PMID- 8862038
TI  - Steroidal saponins from Smilax officinalis.
AB  - Three new steroidal saponins were isolated from the rhizomes of Smilax
      officinalis. The structures of these saponins were established by extensive
      spectral data, hydrolysis and chemical correlation as sarsasapogenin 3-O-beta-D
      glucopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->6 )-beta- D
      glucopyranoside, neotigogenin 3-O-beta-D-glucopyranosyl-(1-->4)-[alpha-L
      arabinopyranosyl-(1-->6 )]-beta- D-glucopyranoside and 25S-spirostan-6 beta-ol 3
      O-beta-D-glucopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->6 )]-beta- D
      glucopyranoside. Acid hydrolysis of the latter compound gave a sapogenin which
      has a new orientation of an hydroxyl on the steroidal skeleton. A route is
      proposed for the biogenesis of the latter sapogenin which is an uncommon
      steroidal aglycone.

PMID- 8862039
TI  - Phenylethanoid glycosides from Stachys officinalis.
AB  - From the aerial parts of Stachys officinalis, six new phenylethanoid glycosides,
      named betonyosides A-F, and six known phenylethanoid glycosides, acetoside,
      acetoside isomer, campneosides II, forsythoside B and leucosceptoside B, were
      isolated and their structures were elucidated from spectroscopic and chemical
      evidence. Campneosides II were separated into two epimers.

PMID- 8862040
TI  - Xanthones from Hypericum roeperanum.
AB  - Four new xanthones have been isolated from the roots of Hypericum roeperanum.
      Their structures have been established by a combination of spectroscopic and
      chemical methods as 1,6-dihydroxy-5-methoxy-4',5'-dihydro-4',4',5'
      trimethylfurano- (2',3':3,4)-xanthone (5-O-methyl-2-deprenylrheediaxanthone B),
      1,6-dihydroxy-5-methoxy-6',6'-dimethylpyrano-(2',3':3,4)-xanthone (5-O
      methylisojacareubin), 1,3,5,6-tetrahydroxy-2-(2',2'-dimethyl-4'-isopropenyl)
      cyclopen tanylxanthone (5-O-demethylpaxanthonin) and 1,3,5,6-tetrahydroxy-4-trans
      sesquilavandulylxanthone (roeperanone). In addition, 2-hydroxyxanthone, 5-hydroxy
      2-methoxyxanthone, 1,5-dihydroxy-2-methoxyxanthone, 2-deprenyl rheediaxanthone B,
      isojacareubin and calycinoxanthone D have been isolated and characterized. Some
      of the isolated xanthones exhibited antifungal activity against Candida albicans.

PMID- 8862041
TI  - Flavonoids from Epimedium wanshanense.
AB  - A novel flavonol glycoside named wanepimedoside A was isolated from the whole
      plant of Epimedium wanshanense, along with fifteen known flavonoids,
      anhydroicaritin, desmethylanhydroicaritin, icarisid I and II, quercetin,
      ikarisoside A and B, sagittatoside B, 2"-O-rhamnosylicarisid II, icariin, 2"-O
      rhamnosylikarisoside A, epimedin B, epimedin C, and diphylloside A and B.

PMID- 8862042
TI  - Edward Jackson in 1896: a man and his specialty at a crossroads. LIII Edward
      Jackson Memorial Lecture: Part 1.
AB  - PURPOSE: To review the life of Dr. Edward Jackson and his contributions to
      American medicine and ophthalmology, using as a reference point 1896, the year of
      the founding of the American Academy of Ophthalmology. METHODS: Review of
      published materials by and about Edward Jackson and other historical materials to
      evaluate Dr. Jackson's contributions to and the status of American ophthalmology
      during the late nineteenth and early twentieth centuries. RESULTS: Eighteen
      ninety-six was a seminal year for Dr. Jackson. He assumed a leadership role in
      American ophthalmology and medicine while overcoming personal tragedy and the
      difficult transition from being part of the Eastern establishment to becoming "a
      great champion of the West." CONCLUSION: The issues and events of 1896, and their
      evolution and repercussions in subsequent decades, confirm that Edward Jackson
      was a major figure in shaping modern American ophthalmology.

PMID- 8862043
TI  - The visual function of professional baseball players.
AB  - PURPOSE: To measure the visual acuity, stereoacuity, and contrast sensitivity of
      professional baseball players. METHODS: Three hundred eighty-seven professional
      baseball players underwent several tests of visual function including distance
      visual acuity. Stereoacuity was evaluated at near by the Randot test and at
      distance by both contour and random dot targets. Distance stereoacuity was also
      tested under timed and untimed conditions. Contrast sensitivity was evaluated by
      the Vision Contrast Test System, Contrast Sensitivity Viewer, and Binocular
      Visual Acuity Tester. RESULTS: Visual acuity (measured with players' regular
      distance correction) in 774 eyes ranged from 20/8.89 to 20/100. Near stereoacuity
      ranged from 23 to 37 seconds of arc, mean untimed distance contour stereoacuity
      from 55 to 35 seconds of arc, and mean untimed distance random dot stereoacuity
      from 98 to 76 seconds of arc. The results under timed conditions were 86 to 65
      seconds of arc (timed distance contour stereoacuity) and 104 to 83 seconds of arc
      (timed distance random dot stereoacuity). Statistically significant differences
      were found between major and minor league players on tests of untimed distance
      contour and random dot stereopsis, and on contrast sensitivity testing with the
      3.0- and 6.0-cpd gratings using the Contrast Sensitivity Viewer. CONCLUSIONS:
      Professional baseball players have excellent visual skills. Mean visual acuity,
      distance stereoacuity, and contrast sensitivity are significantly better than
      those of the general population.

PMID- 8862044
TI  - Variations in the clinical course of submacular hemorrhage.
AB  - PURPOSE: To assess variations in the clinical course of submacular hemorrhages.
      METHODS: We reviewed fundus photography charts taken of patients during a 27
      month period. Thirty-one eyes of 31 patients with submacular hemorrhages under
      the foveal avascular zone were reviewed. RESULTS: In 20 of the eyes, the
      underlying etiology was age-related macular degeneration (ARMD). The other 11
      eyes had various underlying conditions, including macroaneurysms (two), presumed
      ocular histoplasmosis syndrome (two), trauma (one), Valsalva's retinopathy (one),
      idiopathic central serous choroidopathy (one), diabetic retinopathy (two),
      central retinal vein occlusion (one), and choroidal rupture (one). Of the eyes
      with ARMD (mean follow-up, 29 months), eight (40%) of 20 showed an improvement in
      visual acuity (> or = 2 Snellen lines), six (30%) of 20 had a final visual acuity
      of 20/80 or better, and three (15%) had a final visual acuity of 20/40 or better
      (range, 20/25 to 20/80). Of the eyes without ARMD (mean follow-up, 29 months),
      five (45) of 11 had an improvement in visual acuity and five (45%) of 11 attained
      a final visual acuity of 20/40 or better (range, 20/20 to 20/40). The best
      predictive factor for poor final visual acuity was the presence of a subretinal
      neovascular membrane. CONCLUSIONS: Patients with submacular hemorrhage may have
      spontaneous improvement in visual acuity without surgery. Patients without
      subretinal neovascular membranes had a better visual improvement rate.

PMID- 8862045
TI  - Spontaneous regression of neovascularization at the disk and elsewhere in
      diabetic retinopathy.
AB  - PURPOSE: To report three cases of spontaneous regression of new vessels of the
      disk and elsewhere in proliferative diabetic retinopathy. METHODS: We
      retrospectively examined the clinical records of three young women (27, 26, and
      19 years old) with insulin-dependent diabetes mellitus (for 16, eight, and 17
      years, respectively) associated with other systemic diseases and referred to us
      for treatment of retinopathy. Complete general and ophthalmologic findings,
      visual field, and angiographic and electroretinographic examinations were
      available for each patient. RESULTS: All the patients showed marked, spontaneous
      improvement of their proliferative retinopathy, with regression of new vessels.
      Assessment of metabolic control did not bring to light any noteworthy change
      during the period when the new vessels disappeared. Regression of new vessels was
      associated with a marked improvement in blood-retinal barrier breakdown as
      detected on fluorescein angiograms. CONCLUSIONS: Although very unusual,
      spontaneous regression of neovascularizations in proliferative diabetic
      retinopathy can happen. We can offer no explanation for the regression of the new
      vessels and retinovascular hyperpermeability.

PMID- 8862046
TI  - Retinal hemodynamics in retinitis pigmentosa.
AB  - PURPOSE: To investigate the retinal hemodynamic changes occurring in patients
      with retinitis pigmentosa (RP). METHODS: Bidirectional laser Doppler velocimetry
      and monochromatic fundus photography were used to determine retinal venous
      diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow (Q)
      in the major retinal veins of eight patients with RP and eight age-matched normal
      controls. The retinal vascular regulatory responses to hyperoxia, defined as the
      percent decreases in D (RD), Vmax (RVmax), and Q (RQ) at four to six minutes of
      breathing 100% oxygen, were determined in eight normal subjects and five RP
      patients. RESULTS: Average D, Vmax, and Q +/- S.D. in the largest retinal vein of
      each subject were 106 +/- 14 microns, 1.01 +/- 0.20 cm/sec, and 3.5 +/- 1.3
      microliters/min, respectively, in RP patients, and 166 +/- 12 microns, 1.79 +/-
      0.14 cm/sec, and 14.7 +/- 2.6 microliters/min, respectively, in normal subjects.
      This corresponded to significant decreases from normal of 36% in D, 44% in Vmax,
      and 76% in Q in RP patients (Wilcoxon's rank sum test, P < .001). Average total
      retinal volumetric blood flow rate was 8.2 +/- 2.9 microliters/min in RP patients
      and 37 +/- 4.9 microliters/min in normal subjects, corresponding to a significant
      decrease from normal of 78% (Wilcoxon's rank sum test, P < .001). In RP patients,
      the regulatory responses to hyperoxia (RD, RVmax, and RQ) were similar to those
      observed in normal subjects. RESULTS: Retinal blood flow is significantly
      decreased in patients with RP, probably as a result of vascular remodeling in
      response to reduced metabolic demand. The regulatory responses to hyperoxia are
      similar to those of normal subjects. Measurements of retinal blood flow may help
      assess the progression of the disease and the effects of treatment.

PMID- 8862047
TI  - Irradiated uveal melanomas: cytopathologic correlation with prognosis.
AB  - PURPOSE: We analyzed the additional prognostic information from cytopathologic
      data obtained at the time of uveal melanoma irradiation. METHODS: Fine-needle
      aspiration biopsies (FNABs) were performed and reviewed in a masked manner. These
      data and standard prognostic variables were correlated with survival and local
      tumor recurrence using Kaplan-Meier and Cox model statistical techniques.
      RESULTS: Cytopathologic assessment of cell type added to prognostic accuracy. In
      116 patients, the percentage of epithelioid cells on FNAB and ciliary body
      involvement were most strongly correlated with melanoma-related mortality.
      CONCLUSIONS: FNAB data improved our prognostic accuracy in irradiated uveal
      melanoma patients.

PMID- 8862048
TI  - Echographic measurement of optic nerve thickness correlated with neuroretinal rim
      area and visual field defect in glaucoma.
AB  - PURPOSE: To determine whether echographic measurements of the pial diameter of
      the optic nerve are significantly correlated with glaucomatous changes of the
      optic disk and retinal nerve fiber layer. METHODS: In 31 patients with primary
      open-angle glaucoma and 16 normal control subjects, optic nerve thickness was
      determined by measuring the maximal pial diameter of the optic nerve using
      standardized A-scan echography. The optic disks were morphometrically examined
      using color stereo photographs, and the retinal nerve fiber layer was assessed
      using wide-angle red-free fundus photographs. RESULTS: Optic nerve thickness as
      measured echographically decreased significantly (P < .001) with decreasing
      neuroretinal rim area, diminishing visibility of the retinal nerve fiber layer,
      narrowing of the retinal arterioles, enlarging parapapillary atrophy, and
      increasing mean visual field defect. In an intraindividual bilateral comparison,
      side differences in the optic nerve thickness were significantly correlated with
      side differences in neuroretinal rim area (P < .0001), diameter of retinal
      arterioles (P = .003), and visual field defect (P < .0001). In the
      differentiation of normal and glaucomatous eyes, sensitivity and specificity were
      higher for echographic measurements of the optic nerve thickness than for
      parapapillary atrophy and diameter of retinal arterioles but worse than for
      determination of the neuroretinal rim area. CONCLUSIONS: Echographic measurements
      of optic nerve thickness are significantly correlated with glaucomatous changes
      of the optic disk and retinal nerve fiber layer. In patients with opaque media,
      echographic measurement of optic nerve thickness may be helpful in distinguishing
      among normal eyes, eyes with medium advanced glaucoma, and eyes with markedly
      progressed glaucoma.

PMID- 8862049
TI  - Optic nerve head topography in ocular hypertensive eyes using confocal scanning
      laser ophthalmoscopy.
AB  - PURPOSE: To compare measurements of optic nerve topography of ocular hypertensive
      patients with those of normal subjects and primary open-angle glaucoma patients.
      METHODS: Three age-matched study groups of 46 ocular hypertensive patients, 46
      primary open-angle glaucoma patients, and 46 normal subjects were recruited from
      patients and volunteers of a glaucoma referral practice. Optic nerve topography
      was measured using a confocal scanning laser tomograph, the Heidelberg Retina
      Tomograph. The following optic nerve parameters were evaluated: disk area,
      cup/disk area ratio, cup shape, height in contour, rim area, rim volume, maximum
      cup depth, cup area, cup volume, retinal height, and retinal cross-section area.
      For this cross-sectional study, analysis of variance was used to evaluate overall
      differences among the three subject groups and the Tukey-Kramer multiple
      comparison test to evaluate differences between the means of two groups. RESULTS:
      Statistically significant differences among study groups were found for all
      topographic optic nerve parameters evaluated. Despite considerable overlap in
      optic nerve parameter measurements among the study groups, mean values of ocular
      hypertensive eyes were intermediate between those for normal and primary open
      angle glaucoma eyes. Statistically significant differences were found between
      ocular hypertensive and glaucomatous eyes for all optic nerve parameters
      measured, and between ocular hypertensive and normal eyes for disk area, height
      in contour, rim area, and rim volume. CONCLUSIONS: In age-matched groups, mean
      measurements of certain topographic optic nerve parameters of ocular hypertensive
      eyes differ from those of normal and glaucomatous eyes.

PMID- 8862050
TI  - Screening potential corneal donors for HIV-1 by polymerase chain reaction and a
      colorimetric microwell hybridization assay.
AB  - PURPOSE: Current screening of potential corneal donors for human immunodeficiency
      virus type 1 (HIV-1) involves serologic detection of antibodies to the virus.
      However, this approach cannot detect infection during the seronegative window
      period of the disease. We therefore evaluated the polymerase chain reaction (PCR)
      assay for viral nucleic acid as a possible alternative to screening cadaveric
      blood for HIV-1. METHODS: Blood specimens from cadavers diagnosed at autopsy with
      acquired immunodeficiency syndrome (AIDS) (n = 21), at high risk for HIV-1
      infection (n = 47), and at no known risk (n = 350) were screened by PCR for HIV-1
      proviral DNA and human leukocyte antigen (HLA)-DQ alpha sequences, and for HIV
      antibodies. RESULTS: All AIDS group samples were seropositive; of these, 18 (86%)
      and 20 (95%) of 21 were positive for HIV by PCR of proteinase K- and Chelex
      extracted pellets, respectively. The seropositive samples negative by PCR testing
      were shown to inhibit PCR amplification. Nine (19%) of 47 high-risk specimens
      were HIV-positive. The no-known-risk group yielded negative results. The overall
      sensitivities for PCR in the proteinase K- and Chelex-treated groups were 90% and
      97%, respectively, compared with Western blot reactivity. If PCR-inhibitory
      samples and HLA-DQ alpha-negative samples had been eliminated, sensitivity would
      have been 100%. Specificity was 100% for each group. CONCLUSIONS: Screening
      cadaveric blood by PCR may be feasible, but further refinement of the assay and
      blood specimen collection practices will be necessary for it to become routine.
      Future studies should focus on optimizing specimen procurement and preparation to
      reduce or eliminate specimens that inhibit PCR.

PMID- 8862051
TI  - Hyperbaric oxygen therapy for nonarteritic anterior ischemic optic neuropathy.
AB  - PURPOSE: To evaluate the effectiveness of hyperbaric oxygen therapy in reducing
      optic nerve damage in acute nonarteritic anterior ischemic optic neuropathy.
      METHODS: Twenty-two eyes in 20 patients with acute nonarteritic anterior ischemic
      optic neuropathy were treated with hyperbaric oxygen (100% oxygen, 2.0 absolute
      atmospheres of pressure) in two 90-minute inhalation sessions per day for ten
      days. Changes in mean visual acuity and mean sensitivity loss were compared with
      those of 27 untreated control patients with acute nonarteritic anterior ischemic
      optic neuropathy, and proportions of patients with a change in acuity or mean
      sensitivity loss were compared with controls. Similar analysis was performed on
      subgroups based on time delay from symptom onset to therapy. RESULTS: Mean values
      for visual acuity were increased at final examination in both groups; although
      the increase was greater in controls, the difference was not statistically
      significant. Mean visual field sensitivity loss was minimally increased; although
      the increase was smaller in controls, the difference between groups was not
      significant. There was no significant difference between groups in proportions of
      patients with change in acuity score or mean sensitivity loss. Stratification by
      time delay to therapy did not suggest that treatment within nine days produced
      better visual results than that for either controls or those treated later.
      CONCLUSIONS: Hyperbaric oxygen therapy using 100% oxygen and 2.0 absolute
      atmospheres of pressure did not produce a significant improvement in visual
      acuity or visual field for patients with acute nonarteritic anterior ischemic
      optic neuropathy.

PMID- 8862052
TI  - Visual field loss in HIV-positive patients without infectious retinopathy.
AB  - PURPOSE: To determine the extent of vision loss in a cross-sectional study of HIV
      positive individuals who had no infectious retinopathy. METHODS: Visual field
      loss was determined by computerized achromatic automated perimetry and short
      wavelength automated perimetry in both eyes in 65 HIV-positive individuals
      without infectious retinopathy and in one randomly selected eye each in 57 age
      matched normal controls. Results were analyzed using the global index of mean
      defect and the Glaucoma Hemifield Test, and significance was determined through
      analysis of variance, chi-square, and Tukey-Kramer tests. RESULTS: We found that
      HIV-positive patients, compared with age-matched HIV-negative controls,
      demonstrated significant (at least P < .01) localized defects as well as an
      increased mean defect. The HIV-positive patients also had a significantly greater
      number of defective points, especially on short-wavelength automated perimetry,
      even while ophthalmoscopic examination and fundus photographs suggested that the
      retinas were normal. CONCLUSIONS: There is a significant loss of visual function
      in HIV-positive individuals that is not the result of infectious retinopathies.
      The finding by short-wavelength perimetry of more severe defects suggests that
      the vision defects are not caused by attentional or other suprachiasmatic
      problems because the neurologic difficulty of both achromatic and short
      wavelength perimetry is similar. The effects of this vision loss on the daily
      living and occupational tasks of this population require further study.

PMID- 8862053
TI  - Unilateral congenital ptosis with ipsilateral superior rectus muscle overaction.
AB  - PURPOSE: Congenital ptosis may be accompanied by weakness of the ipsilateral
      superior rectus muscle. We report the finding of a hypertropia of the ipsilateral
      eye in patients with isolated unilateral congenital ptosis that became manifest
      only in upgaze. METHODS: Seventy consecutive patients with congenital ptosis were
      recalled and 58 reexamined. Examination included assessment of visual acuities,
      palpebral apertures, levator muscle function, and an orthoptic examination.
      Particular attention was paid to the assessment of upgaze. RESULTS: Thirty-eight
      patients had an isolated unilateral congenital ptosis. Four patients had
      bilateral ptosis, six had upgaze deficits, and ten others had a variety of other
      syndromes associated with ptosis. Seventeen of the 38 patients with isolated
      unilateral congenital ptosis were found to have an ipsilateral hypertropia on
      upgaze. The size of the vertical deviation varied from 5 to 30 prism diopters
      and, in the more severe cases, produced a cosmetic problem that became more
      noticeable after successful ptosis surgery. In one of these patients, a superior
      rectus muscle posterior fixation suture was effective in reducing the
      hypertropia. CONCLUSION: Of a number of possible causes for the ipsilateral
      hypertropia in upgaze in patients with unilateral congenital ptosis that we
      observed either a misdirection syndrome within the superior division of the
      oculomotor nerve or an exaggerated Bell's reflex is the most likely.

PMID- 8862055
TI  - Eye surgeons--seize the opportunity.

PMID- 8862054
TI  - Positron emission tomography in diagnosing brainstem vascular lesions that cause
      abnormal eye movements.
AB  - PURPOSE: To evaluate the efficacy of positron emission tomography (PET) in aiding
      in the diagnosis of brainstem infarctions that cause abnormal eye movements.
      METHOD: Cerebral glucose metabolism was examined by PET with 18F
      fluorodeoxyglucose as a tracer in five normal control subjects and six patients
      with abnormal eye movements. The PET images were registered to and superimposed
      on magnetic resonance images (MRIs). RESULTS: All control subjects showed little
      asymmetry of glucose metabolism in the brainstem, whereas all six patients
      demonstrated areas of low glucose metabolism in the brainstem. Areas of low
      metabolism seen by PET were wider than they appeared to be by MRI; MRIs even
      appeared normal in some patients. Asymmetry index measurements at the level of
      the ischemic lesion ranged between 19% and 45%. CONCLUSIONS: Positron emission
      tomography detected metabolic abnormality in patients with brainstem lesions that
      caused abnormal eye movements. Superimposing PET images on MRIs accurately
      localized abnormally low metabolism in the brainstem. Combined imaging with PET
      and MRI can be used to diagnose ischemic lesions in the brainstem from functional
      (PET) and morphologic (MRI) viewpoints.

PMID- 8862056
TI  - Retinal vein occlusion after trabeculectomy with mitomycin C.
AB  - PURPOSE: To evaluate acute retinal vein occlusion as a potential complication of
      trabeculectomy with mitomycin C in cases of advanced glaucoma. METHODS: The
      records of three patients who developed retinal vein occlusions immediately after
      uncomplicated trabeculectomy with mitomycin C were reviewed. RESULTS: All three
      patients had advanced open-angle glaucoma with total cupping of the optic nerve,
      severe visual field loss, and evidence of systemic vascular disease. A marked
      decrease in intraocular pressure was noted in the postoperative period in all of
      the patients. CONCLUSION: A shift in the lamina cribrosa, associated with the
      perioperative intraocular pressure change, may have contributed to occlusion of
      the venous outflow system in these susceptible patients.

PMID- 8862057
TI  - Total cholesterol and high-density lipoprotein levels as risk factors for
      increased intraocular pressure.
AB  - PURPOSE: To determine whether high-density lipoprotein and total cholesterol
      levels were risk factors for increased intraocular pressure in patients with
      chronic open-angle glaucoma or ocular hypertension. METHODS: We measured total
      cholesterol, high-density lipoprotein, and total cholesterol/high-density
      lipoprotein ratio in 25 patients with open-angle glaucoma or ocular hypertension
      who had taken no glaucoma medications for four weeks. We individually matched
      these patients to 25 control subjects who had no history of open-angle glaucoma
      or ocular hypertension, on the basis of age, race, gender, and history of
      vascular disease or diabetes mellitus. RESULTS: We found no statistical
      difference in the high-density lipoprotein (P = .702) or total cholesterol (P =
      .177) levels or total cholesterol/high-density lipoprotein ratio between groups
      (P = .178, paired t test). CONCLUSION: This study indicates that increased high
      density lipoprotein and total cholesterol levels are not risk factors for
      increased intraocular pressure.

PMID- 8862058
TI  - Bilateral corkscrew episcleral veins from tricuspid incompetence.
AB  - PURPOSE: To use color Doppler imaging in examining a patient with clinically
      diagnosed low-flow carotid-cavernous sinus fistula and a history of rheumatic
      heart disease. METHOD: The flow characteristics of the orbital vessels and the
      internal jugular veins were studied with a 7.0-MHz transducer. RESULTS: Episodic
      arterialization and reversal of blood flow was demonstrated in both superior
      ophthalmic veins. This similar waveform was also seen in both jugular veins.
      CONCLUSION: The presence of tricuspid regurgitation and pulmonary hypertension
      caused increased episcleral venous pressure and the corkscrew appearance, which
      is more commonly associated with carotid-cavernous sinus fistula.

PMID- 8862059
TI  - An infusion temporary keratoprosthesis for pars plana vitrectomy.
AB  - PURPOSE: To develop a temporary keratoprosthesis with integrated infusion cannula
      to minimize retinal complications during pars plana vitrectomy in eyes with an
      opaque cornea. METHODS: The wide-field temporary keratoprosthesis has been
      modified to include an integrated infusion cannula. The 20-gauge cannula runs
      from the periphery of the corneal flange, bends 90 degrees, and enters the eye
      after passing through the periphery of the corneal cylinder. RESULTS: The
      infusion wide-field temporary keratoprosthesis has been used successfully in
      three cases without the need to place a separate infusion, which risks iatrogenic
      retinal breaks or retinal dialyses. Droplet condensation on the posterior surface
      of the infusion temporary keratoprosthesis was reduced compared with the standard
      temporary keratoprosthesis. CONCLUSION: We have developed a wide-field temporary
      keratoprosthesis with an integrated infusion cannula for use during pars plana
      vitrectomy in eyes with severe corneal opacity. This device eliminates the risk
      of complications related to the pars plana infusion cannula.

PMID- 8862060
TI  - Inflammatory opacities of the vitreous in rifabutin-associated uveitis.
AB  - PURPOSE: To describe rifabutin-associated uveitis with opacities in the inferior
      and posterior vitreous in three patients with acquired immunodeficiency syndrome.
      METHOD: Case reports of the three patients are presented. RESULTS: The patients,
      who were being treated with rifabutin and fluconazole, developed anterior and
      posterior uveitis. The posterior uveitis was characterized by white-yellow
      inflammatory opacities located in the inferior and posterior vitreous.
      Discontinuation of rifabutin and the start of topical corticosteroid therapy
      resulted in improvement of the uveitis and visual acuity. CONCLUSION: Recognition
      of rifabutin-associated uveitis with opacities in the inferior and posterior
      vitreous may prevent unnecessary invasive diagnostic and therapeutic procedures.

PMID- 8862061
TI  - Intermediate uveitis and retinal vasculitis as manifestations of cat scratch
      disease.
AB  - PURPOSE: To study the ocular manifestations of systemic Rochalimaea infection.
      METHODS: We examined a healthy 21-year old woman who had floaters in both eyes. A
      bilateral mild vitreitis and multiple foci of retinal vasculitis were found;
      during the ensuing two weeks, exudates appeared over the inferior pars plana. The
      patient owned five kittens but had no history of cat bites or scratches. Serum
      levels of antibodies to Rochalimaea were elevated. RESULT: The retinal vasculitis
      and vitreitis resolved after three weeks of therapy with ciprofloxacin
      hydrochloride without concomitant anti-inflammatory therapy. CONCLUSION:
      Rochalimaea infection should be considered in the differential diagnosis of
      intermediate uveitis and retinal vasculitis.

PMID- 8862062
TI  - Acanthamoeba endophthalmitis in acquired immunodeficiency syndrome.
AB  - PURPOSE: To report the findings of Acanthamoeba endophthalmitis in a patient with
      acquired immunodeficiency syndrome (AIDS). METHODS: A 35-year-old man with AIDS
      and Acanthamoeba infection of the skin and lungs was treated for a granulomatous
      uveitis in the left eye. RESULTS: The left eye developed mutton-fat keratic
      precipitates, iris granulomas, cataract, hypotony, and choroidal infiltrates.
      Aqueous and vitreous specimens were positive for Acanthamoeba cysts. Topical and
      systemic antiamebic medications decreased the inflammation but failed to control
      the infection. CONCLUSIONS: Acanthamoeba infection should be considered in the
      differential diagnosis of uveitis in patients with AIDS.

PMID- 8862063
TI  - Varicella-zoster virus retrobulbar optic neuritis in a patient with human
      immunodeficiency virus.
AB  - PURPOSE: To determine the cause of bilateral retrobulbar optic neuritis followed
      by progressive outer retinal necrosis in a patient with human immunodeficiency
      virus (HIV). METHODS: Extensive ophthalmologic, neurologic, infectious disease,
      rheumatologic, and radiologic examinations were performed. RESULTS: Cerebrospinal
      fluid samples taken after the onset of bilateral retrobulbar optic neuritis and
      before the development of clinical progressive outer retinal necrosis disclosed
      varicella-zoster virus from polymerase chain reaction and viral culture.
      CONCLUSION: Ophthalmologists and neurologists should consider varicella-zoster
      virus optic neuritis as a potential precursor of progressive outer retinal
      necrosis and as a cause of retrobulbar optic neuritis in patients infected with
      HIV.

PMID- 8862064
TI  - Vitreous Hemorrhage complicating laser-induced chorioretinal anastomosis for
      central retinal vein occlusion.
AB  - PURPOSE: To report a severe complication of laser chorioretinal anastomosis for
      central retinal vein occlusion. METHOD: Case report. RESULTS: In the right eye of
      a 62-year-old woman with nonischemic central retinal vein occlusion, retinal
      neovascularization at the laser chorioretinal anastomosis site caused dense
      secondary vitreous hemorrhage. Vitreous hemorrhage prevented laser panretinal
      photocoagulation for subsequent iris neovascularization, necessitating vitrectomy
      surgery to clear the hemorrhage and allow the treatment. CONCLUSION: Laser
      chorioretinal anastomosis can result in severe vitreous hemorrhage and complicate
      efforts to manage later sequelae of central retinal vein occlusion.

PMID- 8862065
TI  - Choroidal neovascular membrane after laser-induced chorioretinal anastomosis.
AB  - PURPOSE: To treat a patient who had a choroidal neovascular membrane after laser
      induced chorioretinal anastomosis for nonischemic central retinal vein occlusion.
      METHODS: A 70-year-old man underwent successful formation of a chorioretinal
      anastomosis for nonischemic central retinal vein occlusion. He subsequently
      developed a choroidal neovascular membrane at the site of the chorioretinal
      anastomosis. RESULTS: The choroidal neovascular membrane at the site of the
      chorioretinal anastomosis was treated successfully with argon laser
      photocoagulation. The anastomosis remained functional. CONCLUSION: We recommend
      that patients who have undergone laser-induced chorioretinal anastomosis for
      nonischemic central retinal vein occlusion be followed up closely for choroidal
      neovascular membrane formation.

PMID- 8862066
TI  - Bilateral papilledema with retinal hemorrhages in association with cerebral
      venous sinus thrombosis and paroxysmal nocturnal hemoglobinuria.
AB  - PURPOSE: To report a patient with paroxysmal nocturnal hemoglobinuria who
      complained of transient obscurations of vision and exhibited bilateral
      papilledema with retinal hemorrhages. METHODS: Case report. Computed tomography
      did not demonstrate any abnormality but magnetic resonance imaging disclosed
      signs of cerebral venous sinus thrombosis. RESULTS: The patient was treated with
      subcutaneous low molecular weight heparin and intravenous corticosteroids.
      Symptoms improved within one week and ophthalmoscopic signs resolved within four
      months. CONCLUSION: Bilateral papilledema with extensive retinal hemorrhages may
      be a sign of cerebral venous sinus thrombosis, a reported devastating
      complication of paroxysmal nocturnal hemoglobinuria. Thus, any patient with
      suspected cerebral venous sinus thrombosis should undergo magnetic resonance
      imaging, even when results of computed tomography are normal.

PMID- 8862067
TI  - Recurrence of a choroidal neovascular membrane in a patient with punctate inner
      choroidopathy treated with daily doses of thalidomide.
AB  - PURPOSE: To determine whether thalidomide therapy can prevent a recurrence of a
      choroidal neovascular membrane in a patient with punctate inner choroidopathy.
      METHODS: Case report. In a 38-year-old woman with bilateral punctate inner
      choroidopathy, thalidomide therapy was initiated three days after laser
      photocoagulation of a choroidal neovascular membrane. RESULTS: The patient had a
      recurrence of the choroidal neovascular membrane eight months after the start of
      thalidomide therapy. CONCLUSIONS: The failure of thalidomide to prevent a
      recurrence of a choroidal neovascular membrane in this patient suggests that this
      medication may have only a limited benefit in preventing recurrences of choroidal
      neovascular membranes.

PMID- 8862068
TI  - Plasmacytoma manifesting as recurrent cellulitis and hematic cyst of the orbit.
AB  - PURPOSE: To describe a patient with recurrent periorbital cellulitis and orbital
      blood cyst as the initial manifestation of primary extramedullary plasmacytoma.
      METHODS: The chart, imaging studies, and histopathologic examination results and
      literature on the subject were reviewed. RESULTS: Orbital surgery disclosed a
      hematic cyst along with a solitary plasma cell tumor. CONCLUSIONS: Periorbital
      cellulitis and pain can be a manifestation of a plasma cell tumor. Bleeding may
      occur within a necrotic orbital tumor.

PMID- 8862069
TI  - Balloon catheter dilatation for treatment of congenital nasolacrimal duct
      obstruction.

PMID- 8862070
TI  - The treatment of Graves' ophthalmopathy in an incidence cohort.

PMID- 8862071
TI  - The management of gallstone pancreatitis in the era of laparoscopic
      cholecystectomy.

PMID- 8862072
TI  - Pancreatic pseudocysts following acute pancreatitis.
AB  - BACKGROUND: Pancreatic pseudocysts (PP) following acute pancreatitis have
      traditionally been approached by observation to allow cyst maturation. However,
      recent evidence suggests a selective approach toward management is indicated.
      METHODS: We retrospectively reviewed the presentation, operative management, and
      outcome of patients developing PP following acute pancreatitis since 1988. PP
      related to chronic pancreatitis were excluded. RESULTS: Twenty-seven patients
      were identified, 17 with giant PP (> 10 cm) and 10 with PP less than 10 cm.
      Groups were not different with respect to age and etiology of pancreatitis,
      predominantly biliary. Patients with giant PP had a significantly greater number
      of Ranson criteria at presentation and underwent drainage procedures earlier
      following their initial presentation. With respect to giant PP, 7 patients
      underwent internal drainage all via cystogastrostomy with 5 complications. Nine
      of 10 patients underwent urgent operation via external drainage. There were 3
      pancreatic fistulas in this group. The morbidity and mortality rates for giant PP
      were 65% and 18% respectively. With respect to smaller PP, 8 underwent internal
      drainage with 1 death (mortality rate 10%). External drainage was performed in 2
      patients with 1 pancreatic fistula (morbidity 10%). CONCLUSIONS: Patients with PP
      and a high Ranson score following acute pancreatitis are at significant risk for
      giant PP formation. Expectant management of giant PP is associated with higher
      morbidity and mortality than small PP suggesting that earlier external drainage,
      before clinical deterioration, may be beneficial. To be accurate, comparisons of
      outcomes for various treatment modalities must take into consideration PP size.

PMID- 8862073
TI  - Safety and long-term efficacy of revisional surgery in severe obesity.
AB  - BACKGROUND: A National Institutes of Health Consensus Conference in 1991
      established gastric surgery as accepted therapy for the treatment of severe
      obesity. The increasing prevalence of obesity in the United States, and the
      increasing numbers of patients undergoing gastric surgery for severe obesity,
      result in substantial numbers of patients being considered for revisional
      surgery. The indications and efficacy of revisional surgery remain controversial.
      METHODS: Sixty-three patients were followed prospectively after undergoing
      revisional surgery for obesity between 1981 and 1994. All patients had previously
      undergone obesity operations. Weight data were recorded at the time of original
      obesity surgery, at revisional surgery, and at most current follow-up.
      Complications following revisional surgery were monitored. RESULTS: The follow-up
      in the group is 98%. Revisional surgery after obesity surgery was associated with
      a 0% mortality rate and a serious complication rate of 16%. Body mass index (BMI)
      at the time of original surgery was 50 +/- 10 kg/m2, at revisional surgery 39 + 9
      kg/m2, and at recent follow-up 34 +/- 10 kg/m2 (P < 0.001 vs original BMI). Those
      patients whose original BMI was > 50 kg/m2 lost significantly more weight (P <
      0.0001) than those with an original BMI < 50 kg/m2. CONCLUSIONS: Revisional
      gastric surgery is safe and does provide patients with the opportunity to achieve
      long-term weight control.

PMID- 8862074
TI  - Perforated colorectal carcinomas.
AB  - BACKGROUND: Colorectal carcinomas that present with perforation are stated in the
      literature to carry a poor prognosis. This study is to verify or refute the
      dismal connotation associated with perforated colorectal carcinomas (PCCs).
      METHODS: A retrospective analysis of 1551 patients with colorectal carcinoma
      revealed that 51 (3.3%) patients presented with perforation. Mary Immaculate and
      St. John's Queens Hospital Divisions of the Catholic Medical Center of Brooklyn
      and Queens chart and tumor board data were retrieved for the period 1983 through
      1993. RESULTS: Localized perforation with abscess formation occurred in 31 (61%)
      patients, and free perforation with generalized peritonitis in occurred 20 (39%)
      patients. Sixteen (31%) patients had distant metastasis at diagnosis with a mean
      survival of only 6 months. Overall operative mortality rate was 12%, and overall
      5-year survival rate was 32%. By excluding 16 patients with documented Stage IV
      disease at diagnosis and 6 operative mortalities (3 of whom also had Stage IV
      disease at diagnosis), the remaining 32 patients had a mean survival of 59 months
      and a 5-year survival of 58%. CONCLUSION: In view of the 58% survival in our
      subset of patients, aggressive management is recommended. This includes
      management of sepsis and radical surgical resection of adjacent involved organs.
      A negative attitude associated with PCC is not substantiated in this
      retrospective 10-year study.

PMID- 8862075
TI  - The mode of lymphatic spread in carcinoma of the bile duct.
AB  - BACKGROUND: Knowing the prevalence of lymph node involvement associated with the
      location of the primary tumor is a prerequisite for operating with curative
      intent in carcinoma of the bile duct. METHODS: We evaluated 80 patients with
      carcinoma of the bile duct or cystic duct to investigate the frequency of lymph
      node involvement, the mode of lymphatic spread, and prognosis, according to the
      location of the primary tumor. RESULTS: The frequency of lymphatic spread of
      carcinomas in the proximal, middle, and distal bile ducts, excluding seven T1
      tumors, was 48%, 67%, and 56%, respectively. With regard to the mode of lymphatic
      spread: (1) a metastatic pathway along the common hepatic artery predominated
      over that to the retropancreatic area in the proximal duct carcinoma group; (2)
      in the middle duct carcinoma group, metastatic lymph nodes were distributed
      widely, involving nodes around the superior mesenteric artery or at the para
      aortic area; and (3) in the distal duct carcinoma group, metastatic nodes
      generally were localized around the head of the pancreas. CONCLUSIONS:
      Understanding the mode of the lymphatic spread according to the primary tumor may
      be helpful for choosing the appropriate surgical approach with curative intent in
      bile duct carcinoma.

PMID- 8862076
TI  - Alternating floxuridine and 5-fluorouracil hepatic arterial chemotherapy for
      colorectal liver metastases minimizes biliary toxicity.
AB  - BACKGROUND: The goals of this study of a hepatic arterial infusion (HAI) regimen
      of alternating floxuridine and 5-fluorouracil were to evaluate the treatment
      related toxic effects, the antitumor response rate, and patient survival.
      METHODS: Fifty-seven consecutive patients were treated with implanted HAI pumps
      and received a regimen of alternating floxuridine (0.1 mg/kg/day continuous HAI
      for 7 days) followed by a weekly HAI pump bolus of 5-fluorouracil (15 mg/kg for 3
      weeks). Any changes in treatment plan because of toxicity, antitumor response,
      and survival were recorded. RESULTS: Thirty-one (54.4%) patients responded to
      this HAI regimen; 14 (24.5% )patients had stable disease, and 12 (21.1%)
      progressed during treatment. Responders or patients with stable disease had a
      significantly (P < 0.05) improved survival rate (19 months median) compared with
      patients in whom disease progressed (12 months median). Two (3.5%) patients
      developed biliary sclerosis and 12 (21.1%) had mild transient liver function
      abnormalities. The liver alone or in combination with another area was the site
      of first progression of disease in 40 (70.2%) patients. CONCLUSIONS: This regimen
      had reversible or no hepatobiliary toxicity in more than 95% of patients. Tumor
      reduction or stabilization of disease was observed in 79% of the patients, who
      had a median survival of 19 months. Reduced toxicity and more effective
      chemotherapeutic regimens may increase the likelihood of survival after HAI
      chemotherapy for unresectable colorectal liver metastases.

PMID- 8862077
TI  - A comparison of the pathophysiologic effects of carbon dioxide, nitrous oxide,
      and helium pneumoperitoneum on intracranial pressure.
AB  - BACKGROUND: Previous studies have suggested that diagnostic laparoscopy may be
      contraindicated in multiple trauma patients with closed head injuries because of
      the detrimental effects of carbon dioxide (CO2) pneumoperitoneum on intracranial
      pressure (ICP). In this study we compared the effects of two alternative
      inflation gases, helium (He) and nitrous oxide (N2O), against the standard agent
      used in most hospitals, CO2. ICP was monitored in experimental animals both with
      and without a space occupying intracranial lesion designed to simulate a closed
      head injury. METHODS: Twenty-four domestic pigs (mean, 30 kg) were divided into
      four groups (6 CO2, 6 He, 6 N2O, and 6 control animals without insufflation). All
      animals were monitored for ICP, intraabdominal pressure, mean arterial pressure,
      end-tidal CO2 (ETCO2), and arterial blood gases. These parameters were measured
      for 30 minutes prior to introducing a pneumoperitoneum and then for 80 minutes
      thereafter. The measurements were repeated after artificially elevating the ICP
      with a balloon placed in the epidural space. RESULTS: The mean ICP increased
      significantly in all groups during peritoneal insufflation compared with the
      control group (P < 0.005). The CO2-insufflated animals also showed a significant
      increase in PaCO2 (P < 0.05) and ETCO2 (P < 0.05), as well as a decrease in pH (P
      < 0.05). After inflating the epidural balloon the ICP remained significantly
      higher in animals inflated with CO2 as compared with the He and N2O groups (P <
      0.05). CONCLUSIONS: Peritoneal insufflation with He and N2O resulted in a
      significantly less increase in ICP as compared with CO2. That difference was most
      likely due to a metabolically mediated increase in cerebral perfusion (PaCO2) in
      the CO2 group. Further studies need to be conducted to determine the safety and
      efficacy of using He and N2O as inflation agents prior to attempting diagnostic
      or therapeutic laparoscopy in patients with potential closed head injuries.

PMID- 8862078
TI  - Splenectomy in patients with sickle-cell disease.
AB  - BACKGROUND: Splenic complications of sickle-cell disease (SCD) are associated
      with morbidity, and in some it may lead to mortality. This paper presents our
      experience with 43 patients with SCD who had splenectomy as part of their
      management. PATIENTS AND METHODS: The records of 43 patients with SCD who had
      splenectomy were examined for age at operation, sex, hemoglobin (Hb)
      electrophoresis, indication for splenectomy, pre- and postoperative medications,
      operative procedures, and postoperative complications. RESULTS: The indications
      for splenectomy were acute splenic sequestration crisis (ASSC) in 21 patients,
      hypersplenism in 15, and splenic abscess in 7. In 17 patients, the spleen was
      also found to be massively enlarged causing discomfort and intervening with
      everyday activity. For those with hypersplenism, there was a significant
      postoperative increase in total Hb (P < 0.0001), hematocrit (P < 0.0001), white
      blood cells (P < 0.0001), and platelet count (P < 0.0001). CONCLUSIONS: With
      careful perioperative management and proper follow-up, splenectomy in patients
      with SCD is beneficial in reducing their transfusion requirements and its
      attendant risks, eliminating the discomfort from mechanical pressure of the
      enlarged spleen, avoiding the risks of ASSC, and managing splenic abscess.

PMID- 8862079
TI  - Is the pectoralis myocutaneous flap in intraoral and oropharyngeal reconstruction
      outdated?
AB  - METHODS: Our experience with 224 immediate pectoralis major myocutaneous flap
      reconstructions in patients with carcinomas of the oral and oropharyngeal
      cavities is presented. RESULTS: Although flap-related complications developed in
      53% of the patients, all flaps survived, and we had no major skin paddle loss.
      The incidence of reoperation due to flap-related complications was 2%. All other
      complications were minor and did not affect the length of hospitalization.
      Analysis showed no significant risk factors for the development of complications.
      Because of fistula formation, infection, or metal exposure, plate removal was
      necessary in 10% of the AO fixation plates used in cases of mandibular swing.
      This occurred in 68% of the anterior and 22% of the lateral mandibular
      reconstructions performed with a reconstruction plate (P < 0.05). CONCLUSIONS: We
      conclude that a reconstruction plate is unsatisfactory for anterior mandibular
      continuity reconstruction and debatable for lateral mandibular reconstruction. At
      present, anterior defects are reconstructed with free vascularized osteocutaneous
      flaps that should probably also be used for lateral mandibular reconstruction.
      Furthermore, in a large number of series, it is reported that free flaps also
      have high complication rates and 5-10% flap loss. As all pectoralis major flaps
      survived in our series, it still remains a good choice in intraoral and
      oropharyngeal reconstruction when there is no necessity to reconstruct bone.

PMID- 8862080
TI  - Risk factors of tracheostomal recurrence after laryngectomy for laryngeal
      carcinoma.
AB  - BACKGROUND: Tracheostomal recurrence after total laryngectomy for laryngeal
      carcinoma has a poor prognosis. The independent risk factors of tracheostomal
      recurrence are, however, not well documented. METHODS: This is a multivariate
      analysis of the risk factors of tracheostomal recurrence after total laryngectomy
      for 322 laryngeal squamous cell carcinomas. The factors included in the analysis
      were sex, age, tumor stage, sites of tumor involvement, preoperative airway
      obstruction, preoperative tracheostomy, extent of surgical resection,
      radiotherapy, and pathological resection margin. RESULTS: Seventeen (5%) patients
      developed tracheostomal recurrence. Univariate analysis showed that preoperative
      airway obstruction, subglottic involvement, and postcricoid extension were
      significant factors associated with tracheostomal recurrence. Multivariate
      analysis using logistic regression method showed that both subglottic and
      postcricoid involvement were independent predisposing factors for tracheostomal
      recurrence. The tracheostomal recurrence rates were 2% in patients without the
      risk factor and 10% in patients with the presence of one or both risk factors.
      CONCLUSIONS: Subglottic and postcricoid involvement were independent risk factors
      for tracheostomal recurrence.

PMID- 8862081
TI  - Octreotide diminishes luminal nutrient transport activity, which is reversed by
      epidermal growth factor.
AB  - BACKGROUND: Octreotide (SMS) is a somatostatin analogue utilized in patients with
      short bowel syndrome (SBS) to decrease output. It may inhibit small bowel
      adaptation by blocking the secretion of trophic hormones such as epidermal growth
      factor (EGF). This study delineates the effects of SMS and EGF on nutrient
      transport in SBS. METHODS: One week after 70% jejunoileal resection, 20 New
      Zealand White rabbits (2 kg) received subcutaneous infusions of saline or EGF
      (1.5 micrograms/kg/hr) and injections of saline or SMS s.q.b.i.d. The study
      groups were EGF/saline, saline/saline, saline/SMS, and EGF/SMS. After 7 days of
      infusion, intestinal brush border membrane vesicles were prepared and nutrient
      transport measured. RESULTS: SMS reduced active nutrient transport. Kinetics
      confirmed this was secondary to a reduction in functional carriers in the brush
      border membrane, without a change in carrier affinity. The coinfusion of EGF
      ameliorated this effect. On an individual basis, EGF alone did not significantly
      increase nutrient transport, but when taken as a group, nutrients transport was
      upregulated 26%. CONCLUSIONS: SMS is detrimental to small bowel adaptation. EGF
      reverses this effect and may benefit patients with SBS who require SMS to control
      high intestinal output.

PMID- 8862083
TI  - A simple device for closure of fasciotomy wounds.
AB  - Early decompressive fasciotomy is essential in the prevention of the sequelae of
      compartment syndrome. Many techniques have been described for the closure of the
      fasciotomy wound, and controversy exists as to which method is the best. Primary
      closure is often impossible secondary to tissue retraction and edema. Split
      thickness skin grafting leaves a thin, insensate, and often aesthetically
      unpleasing result. Gradual mechanical dermal apposition has been used with
      increasing frequency, and has been shown to be effective in the closure of
      fasciotomies, but often takes 7-10 days for closure. We present our experience
      with the STAR, a mechanical method of fasciotomy wound closure that is effective
      in 2-4 days, and is extremely simple to use.

PMID- 8862082
TI  - How does infected bile affect the postoperative course of patients undergoing
      laparoscopic cholecystectomy?
AB  - OBJECTIVES: To assess the rate of infected bile in patients undergoing
      laparoscopic cholecystectomy (LC) and to study the influence on the postoperative
      infective complications in this group of patients. METHODS: Bile samples of 247
      patients undergoing LC were collected and cultured for aerobic and anaerobic
      bacteria. All patients were given prophylactic antibiotics. RESULTS: The overall
      rate of infected bile was 12.8% (56 positive cultures); of these, 54 were aerobic
      and 2 anaerobic bacteria. Only 2 patients developed infection at the umbilical
      site, and in both, the bile was sterile. None of the patients with positive bile
      cultures developed any signs of infection during a mean follow-up period of 26
      months. CONCLUSION: The overall rate of septic complications following LC is
      extremely low, and at least in our study no correlation was found between
      infected bile and septic complications.

PMID- 8862084
TI  - The crochet hook method of stab avulsion phlebectomy for varicose veins.
AB  - Excision of varicose veins through ministab incisions is currently the choice for
      the removal of varicose vein clusters. The crochet hook technique of stab
      avulsion phlebectomy is described in this paper. This surgical method for the
      treatment of varicose veins has been widely utilized in a residency training
      environment during the last twelve years and has been used by the senior author
      for more than 20 years. The technique is easily mastered, cost effective, and has
      excellent therapeutic and cosmetic results.

PMID- 8862085
TI  - A new concept for implementation of a required general surgery clerkship.
AB  - BACKGROUND: Two years ago our institution abbreviated the junior internal
      medicine and general surgery clerkships to accommodate a 4-week family practice
      clerkship and a 4-week elective clerkship. As a consequence, 1-month mandatory
      internal medicine and general surgery clerkships were placed in the senior year.
      METHODS: The surgical disorders most commonly encountered by the generalist are
      discussed. The senior students spend 4 weeks with a community-based surgeon. All
      lectures are presented by full-time faculty and adhere to the student manual,
      which is designed to coincide with examination material. Three histories and
      physicals are reviewed by the course director to determine utilization of
      critical thinking skills. The development of healthy interpersonal and
      professional relationships is addressed by a 2-hour module on the essentials of
      integrity, compassion, humility, and self-knowledge. A faculty development
      seminar provides an awareness of course objectives and logistics. Student grades
      are determined by the preceptor's evaluation (50%), an in-house written
      examination (50%), and submission of adequate history and physicals. RESULTS:
      Subjective reviews by students (n = 115) reveal that although only 27% of the
      students care to pursue a surgical practice, 85% feel that their time was
      effectively spent and 83% feel that the clerkship should be offered to future
      fourth year medical students. Seventy percent of submitted history and physicals
      (n = 420) exhibit appropriate critical thinking skills. CONCLUSIONS: We are
      currently in the midst of our third year of implementation. The students are
      receiving insight into a surgical approach to common disease processes. History
      and physical examination skills and healthy interpersonal relationships are
      reinforced. Although change is often difficult to accomplish and accept, the
      positive response to the newly formatted senior curriculum has exceeded
      expectations.

PMID- 8862086
TI  - Surgical clerkship performance of traditional and nontraditional students in a
      problem-based learning environment.
AB  - BACKGROUND: To determine whether nontraditional students perform better than
      traditional students during surgical clerkships as reflected on the surgical
      clerkship final examination. METHODS: Retrospective review of medical student
      records from the classes of 1986 through 1993. Students admitted soon after
      completing undergraduate training were identified as "traditional," and those
      having prior careers as "nontraditional." RESULTS: There were 150 traditional and
      72 nontraditional students. The ratio of men to women and admission MCAT scores
      were not significantly different. Traditional students were significantly younger
      and had higher admission grade point averages (GPAs). Nontraditional students
      were more likely to be married and have children. Final examination scores of
      traditional and nontraditional students were not significantly different. MCAT
      scores and college GPAs were the best predictors of final examination
      performance. Married students performed significantly better than single
      students. CONCLUSIONS: There was no significant difference between nontraditional
      and traditional student performance on the surgical clerkship final examination.

PMID- 8862087
TI  - Role of case structure and prior experience in a case-based surgical clerkship.
AB  - BACKGROUND: As case-based methods replaced lectures in a surgical clerkship, the
      influences of case structure and prior experience on learning were investigated.
      METHODS: Early and late third-year students randomly received different cases.
      "Structured" cases had data presented and summarized. "Unstructured" cases
      required questions to faculty for information. Multiple choice tests and
      differential diagnosis activities were administered. An attitudinal questionnaire
      gauged student perceptions. RESULTS: In both multiple choice and differential
      diagnosis activities, the late rotation, "unstructured" group scored higher than
      the "structured" group. Conversely, the early rotation, "unstructured" group
      scored lower than the "structured" group. Combined, rotation, and structure
      significantly affected both multiple choice and differential diagnosis activities
      (ANOVA, P < or = 0.02). Early rotation, "unstructured" students described a more
      enjoyable experience, despite lower evaluation scores. CONCLUSIONS: Surgical
      clerkship case-based learning is profoundly affected by case structure and prior
      clinical experience. Case-based curriculum should be tailored to accommodate
      these interactions.

PMID- 8862088
TI  - The pathogenesis of Staphylococcus aureus in the trauma patient and potential
      future therapies.
AB  - BACKGROUND: Staphylococcus aureus is the most frequently isolated pathogen in the
      trauma patient and uses multiple virulent factors to cause infection. At the
      cellular level, infection begins with the prokaryotic bacterial cell manipulating
      the eukaryotic host cell through its virulent factors. Researching this cellular
      interaction by describing the mechanisms of actions of various virulent factors
      may lead to new preventive therapies which will make the trauma patient less
      susceptible to S aureus infections. METHODS: Surgical, medical, and microbial
      literature was reviewed to provide an update on S aureus pathogenesis. RESULTS:
      Novel future therapies, in addition to antibiotics, are being devised based on
      understanding the molecular nature of S aureus pathogenesis. CONCLUSION: The
      impact of S aureus on trauma will increase as S aureus develops more antibiotic
      resistance and as the trauma population becomes older and includes an increasing
      proportion of immunocompromised patients. To meet the challenge of increased
      virulence, trauma surgeons should be directly involved in the research of
      microbial pathogenesis.

PMID- 8862089
TI  - Immunocytochemical detection of isolated epithelial tumor cells in bone marrow of
      patients with pancreatic carcinoma.
AB  - Epithelial cells in the bone marrow of 42 patients with pancreatic carcinoma were
      identified immunocytochemically with monoclonal antibodies directed to epithelial
      cytokeratins. The occurrence of tumor relapse in patients who underwent complete
      surgical resection was significantly associated with cytokeratin-positivity in
      bone marrow. The presence of these cells in indicative of an increased
      disseminative capability of the primary tumor and defines a new category of
      patients for neoadjuvant therapy.

PMID- 8862090
TI  - Granulocyte-macrophage colony-stimulating factor as infection prophylaxis in high
      risk oncologic surgery.
AB  - BACKGROUND: A method of augmenting host defenses against bacterial pathogens
      could result in a decrease in postoperative infections. Given its effects on
      leukocyte proliferation and function, it is possible that prophylactic
      granulocyte-macrophage colony-stimulating factor (GM-CSF) could reduce the
      incidence and severity of infections in high-risk surgical patients. The current
      study was undertaken to determine the safety and hematologic effects of
      perioperative GM-CSF. METHODS: Cancer patients undergoing operations with a high
      risk of postoperative infection were treated perioperatively for 10 days with
      subcutaneous GM-CSF. Cohorts were treated with GM-CSF at 125 micrograms/m2/day
      (12 patients) and 250 micrograms/m2/day (11 patients). RESULTS: There were no
      severe or life-threatening toxicities associated with GM-CSF. Mean maximum
      neutrophil counts during the first 5 postoperative days were 16.3 +/- 9.14 and
      24.5 +/- 7.60 at 125 and 250 micrograms/m2, respectively (P = 0.04). Only one
      wound infection was diagnosed during this study. CONCLUSIONS: GM-CSF may be
      safely administered perioperatively at doses that augment neutrophil number and
      function. An ongoing randomized clinical trial will determine the impact of GM
      CSF on postoperative infection.

PMID- 8862091
TI  - Effectiveness of extended lymphadenectomy in noncurative gastrectomy.

PMID- 8862092
TI  - Mammographic screenings for women under 50.

PMID- 8862093
TI  - Managed competition. Who will win? Who will lose?

PMID- 8862094
TI  - Guidelines, managed care, and ethics.

PMID- 8862095
TI  - Ethical decision making in managed care.

PMID- 8862096
TI  - The ethics of practice guidelines.
AB  - Practice guidelines, which are assistive tools for clinicians, have a long
      tradition in clinical medicine. Traditionally, these documents were developed by
      physicians to improve quality of care and can provide practitioners with valuable
      medical information and improve objectivity in medical decision making.
      Guidelines development by nonphysician groups is increasing. Guidelines are now
      intended to assist in decreasing costs, in reducing liability risk, and in
      utilization review, among other activities. Despite this enthusiasm for
      guidelines, their development is variable and validity remains largely untested.
      The intended clinical and nonclinical applications of guidelines require critical
      analysis. Practice guidelines are not inherently unethical. However, applications
      of nonmedical values combined with intense pressures on health care provision
      create an environment for guideline misuse. The ethical implications of practice
      guidelines are examined in our article.

PMID- 8862097
TI  - A new resource for managing malpractice risks in managed care.
AB  - The risk of malpractice liability faced by physicians is exacerbated by third
      party intrusions such as those encountered in today's managed care environment.
      The likelihood that a malpractice action will be brought is increased by the
      interaction among patients, families, or physicians who are at high risk for
      litigation and situations (eg, denial of treatment benefits by the managed care
      organization) that create adversity. To prevent the ready translation of resource
      adversity into an adversarial physician-patient-family relationship, a forensic
      psychiatric consultation is recommended.

PMID- 8862098
TI  - Appropriateness of referrals for open-access endoscopy. How do physicians in
      different medical specialties do?
AB  - BACKGROUND: Open-access endoscopy allows nongastroenterologist physicians the
      opportunity to directly schedule elective common endoscopic procedures for their
      patients without having them first examined in the gastrointestinal clinic. There
      are few data as to whether nongastroenterologist physicians in the United States
      schedule patients for appropriate indications. OBJECTIVES: To examine our
      practice to see whether patients undergoing open-access endoscopy were scheduled
      for appropriate indications and to see whether there were differences among
      physicians in various medical specialties. METHODS: We prospectively tracked 310
      consecutive patients scheduled for open-access esophagogastroduodenoscopy (EGD)
      and colonoscopy by nongastroenterologist physicians over a 9-month period in our
      academic practice setting to determine whether the indications for performing the
      procedures were appropriate. The American Society for Gastrointestinal Endoscopy
      criteria (revised in 1992) were used as the standard for comparison. RESULTS:
      Primary care physicians (family practitioners and general internists) did a
      superior job of scheduling patients for appropriate indications for EGD and
      colonoscopy than did non-primary care physicians (internal medicine
      subspecialists and surgeons): 97.0% vs 81.3% for EGD (P = .04) and 84.9% vs 66.7%
      for colonoscopy (P = .02), respectively., CONCLUSIONS: Primary care physicians
      were significantly more likely to schedule patients for open-access EGD and
      colonoscopy for appropriate indications than were non-primary care physicians.
      The frequency of inappropriate indications for colonoscopy referrals was greater
      than for EGD. The reasons for the differences among primary care physicians,
      surgeons, and internal medicine subspecialists require further exploration.

PMID- 8862099
TI  - Association of estrogen replacement therapy with the risk of osteoarthritis of
      the hip in elderly white women. Study of Osteoporotic Fractures Research Group.
AB  - OBJECTIVE: To determine whether postmenopausal estrogen replacement therapy is
      associated with a reduced risk of radiographic findings of osteoarthritis (OA) of
      the hip. DESIGN: Cross-sectional study. SUBJECTS: White women (N = 4366; age, >
      or = 65 years) who were participants in a cohort study of osteoporotic fractures.
      MEASUREMENTS AND METHODS: Radiographs of the pelvis that were obtained in all
      subjects were assessed for radiographic features of OA of the hip on a summary
      scale of 0 (none) to 4 (severe OA). Postmenopausal estrogen use was assessed by
      interview. The association of current and past oral estrogen use with OA of the
      hip was analyzed by using logistic regression, adjusting for potential
      confounding variables (eg, indicators of osteoporosis and correlates of estrogen
      use). RESULTS: Five hundred thirty-nine women (12.3%) had mild or greater
      radiographic findings of OA of the hip in at least 1 hip, and 214 women (4.9%)
      had moderate to severe findings; 17% and 24% of the women were current and past
      users of oral estrogen, respectively. Women who were currently using oral
      estrogen had a significantly reduced risk of any OA of the hip (adjusted odds
      ratio [OR], 0.62; 95% confidence interval [CI], 0.49-0.86) and moderate to severe
      manifestation of disease (OR, 0.54; 95% CI, 0.33-0.88). Current users who had
      taken estrogen for 10 years or longer had a greater reduction in the risk of any
      OA of the hip (OR, 0.57; 95% CI, 0.40-0.82) compared with that of users for less
      than 10 years (OR, 0.75; 95% CI, 0.47-1.24). Current estrogen use for 10 years or
      longer was associated with a nonsignificant trend for a reduced risk of moderate
      to severe symptomatic disease (OR, 0.59; 95% CI, 0.28-1.29). CONCLUSION:
      Postmenopausal estrogen replacement therapy may protect against OA of the hip in
      elderly white women.

PMID- 8862100
TI  - Screening for abdominal aortic aneurysms in a hypertensive patient population.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of preventable
      death in the elderly. OBJECTIVE: To search for an effective screening program for
      the detection of AAA. METHODS: We consecutively and prospectively screened 240
      male, predominantly white, patients, aged 60 to 75 years, by ultrasound for the
      presence of AAA in 2 phases: in screen 1, hypertension (diastolic blood pressure
      reading > 95 mm Hg) was the only selection criterion; in screen 2, we included
      hypertensive patients with a systolic blood pressure level higher than 175 mm Hg
      with or without antihypertensive therapy, transient ischemic attacks and/or
      stroke, and claudication. RESULTS: The yield of AAAs in screens 1 and 2 was 3%
      and 11%, respectively (P < .02, (chi)2 analysis). No AAAs were found in patients
      with uncomplicated hypertension. Of the cardiovascular complications, only
      claudication was independently associated with the presence of AAA (relative
      risk, 5.8; confidence interval, 1.8-18.6; P = .004). CONCLUSIONS: Screening for
      AAA is recommended for elderly white patients with claudication. Uncomplicated
      hypertension by itself is not an indication for screening.

PMID- 8862101
TI  - Safety and tolerability of cholesterol lowering with simvastatin during 5 years
      in the Scandinavian Simvastatin Survival Study.
AB  - BACKGROUND: Long-term safety is an important consideration in the selection and
      use of drugs, such as lipid-lowering agents, that are prescribed to reduce the
      risk of clinical events during long periods. METHODS: The Scandinavian
      Simvastatin Survival Study was designed to evaluate the effects of cholesterol
      lowering with simvastatin on mortality and morbidity in patients with coronary
      heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with
      angina pectoris or previous myocardial infarction and serum cholesterol levels of
      5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly
      assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily,
      or placebo. In addition to previously reported end-point events, detailed
      clinical and laboratory safety data were collected during a median follow-up
      period of 5.4 years (range in survivors, 4.9-6.2 years). RESULTS: The only
      clearly drug-related serious adverse event during the 5.4-year median follow-up
      period was a single reversible case of myopathy. The frequencies of persistent
      elevations of hepatic aminotransferase levels above 3 times the upper limit of
      normal and of nonviral hepatitis in the simvastatin and placebo treatment groups
      were not significantly different. Examination of the lens showed no between-group
      differences, and no previously unrecognized adverse effects of the drug were
      observed. There were no significant between-group differences in adverse events
      in any body system. In particular, the frequency of adverse events related to the
      central nervous system was similar in both groups. CONCLUSION: The safety profile
      of simvastatin, 20 to 40 mg daily, over 5 years was excellent.

PMID- 8862103
TI  - Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme
      disease.
AB  - BACKGROUND: A 2-test approach for the serologic diagnosis of Lyme disease has
      recently been proposed. A positive or equivocal result on a first-stage test (eg,
      an enzyme immunoassay) is followed by a Western immunoblot test. For a sample to
      be considered seropositive for Lyme disease, the immunoblot result must be
      positive. OBJECTIVES: To assess the accuracy of IgM immunoblotting for detection
      of early Lyme disease and to establish interpretative criteria for a commercially
      available immunoblot assay. METHODS: Serum samples from 44 patients with erythema
      migrans were tested by an IgM immunoblot assay. All patients were culture
      positive for Borrelia burgdorferi. Serum samples from 2 different control groups
      were also tested. Interpretative criteria were developed using receiver operating
      characteristic curves. RESULTS: The presence of any 2 IgM bands was found to be
      the optimal criterion for a positive test result, and in patients with illness of
      less than 7 days' duration, this was significantly more sensitive than the
      criterion of any 2 of the 3 specific bands defined by the Centers for Disease
      Control and Prevention/Association of State and Territorial Public Health
      Laboratory Directors Lyme Disease Workgroup (P < .05). Specificity of the
      criterion of any 2 bands was 100% for 1 group of controls but only 96% for the
      more clinically relevant control group; this small difference had a large impact
      on the positive predictive value in populations at low risk for Lyme disease.
      CONCLUSIONS: Using a commercially available immunoblot test kit, the presence of
      any 2 IgM bands is proposed as a positive result. The predictive value of a
      positive IgM immunoblot result, however, is poor in patients with minimal
      clinical evidence for Lyme disease.

PMID- 8862102
TI  - Treatment of the dying in the acute care hospital. Advanced dementia and
      metastatic cancer.
AB  - BACKGROUND: Most Americans die in the acute care hospital, where aggressive, life
      prolonging interventions are readily performed. Although patients with incurable
      illness might prefer palliative care, perceived differences in prognosis by
      physicians may influence the type of care provided. Patients with advanced cancer
      and advanced dementia represent 2 extremes in the use of hospice services and may
      also be treated differently in the acute care hospital. We tested this hypothesis
      and quantitated the use of nonpalliative interventions in hospitalized, incurably
      ill patients. METHODS: Charts of elderly patients with advanced dementia or
      metastatic solid tumor malignancy who died during a 13-month period in a tertiary
      care acute teaching hospital were reviewed. Main outcome measures included the
      number of patients receiving invasive of noninvasive (but complex) diagnostic
      tests, invasive nonpalliative treatments, cardiopulmonary resuscitation, systemic
      antibiotics, and do-not-resuscitate orders. RESULTS: Charts of 164 patients (80
      with dementia and 84 with cancer) were reviewed. Overall, 47% received invasive
      nonpalliative treatments. Controlling for age, sex, length of stay, and insurance
      status, the groups were equally likely to receive nonpalliative treatments (P =
      .75), but patients with dementia were more likely to receive new feeding tubes (P
      = .02). Cardiopulmonary resuscitation was attempted for 24% of each group.
      Patients with cancer more often received invasive (41% vs 13%; P = .002) and
      complex noninvasive diagnostic tests (49% vs 23%; P = .02). Overall, 88% received
      antibiotics, often empirically, but, controlling for neutropenia and invasive
      tests and treatments, patients with dementia were significantly more likely to
      receive antibiotics for an identifiable infection (P = .004). CONCLUSIONS:
      Incurably ill patients often receive nonpalliative interventions at the end of
      life. Patients with cancer receive more diagnostic tests, but patients with
      dementia receive more enteral tube feeding. Patients commonly receive systemic
      antibiotics, often empirically. Cardiopulmonary resuscitation is equally applied,
      but is out of proportion to expected survival.

PMID- 8862104
TI  - A review and economic evaluation of bronchodilator delivery methods in
      hospitalized patients.
AB  - BACKGROUND: Bronchodilator delivery by metered dose inhaler (MDI) to treat
      airflow obstruction is considered to be less expensive and as effective as
      nebulized therapy. OBJECTIVES: To document the utilization of bronchodilator
      delivery methods in a tertiary care Canadian university teaching hospital and to
      perform an economic evaluation. METHODS: A prospective 6-week audit of 4
      preselected hospital wards (respiratory, thoracic surgery, general surgery, and a
      general internal medicine clinical teaching unit) and a cost-minimization
      economic evaluation were performed. Bronchodilator (salbutamol and ipratropium
      bromide) doses, frequency, and delivery methods, either MDI or wet nebulizer
      (WN), were recorded for 95 patients treated with aerosolized bronchodilators.
      Direct costs for medications and hourly wages including benefits and equipment
      were obtained. Time and motion studies identified time allocated to MDI and WN
      delivery. We used sensitivity analyses to test assumptions that could
      significantly affect treatment costs, especially assumptions about medications,
      labor, and spacer devices. Costs are expressed in Canadian dollars (Can$1 =
      US$0.75). RESULTS: Sixty-seven patients (70.5%) were treated with WN, 6 (6.3%)
      with MDI, and 22 (23.2%) with both WN and MDI. Self-administration of salbutamol
      by MDI was the least expensive: $1.27 for 200-microgram doses and $1.73 for 400
      microgram doses compared with $2.62 for a 2.5-mg dose delivered by WN. The
      difference in cost between equivalent treatments (400-microgram MDI vs 2.5-mg WN)
      is only $0.89. Sensitivity analyses showed that MDI was the least expensive
      therapy when self-administration was possible and for all levels of supervision
      if more than 4 minutes was needed to administer a WN treatment. CONCLUSIONS:
      Bronchodilator delivery by WN is commonly prescribed for hospitalized patients
      despite evidence for equivalency of effect using MDI and in the absence of
      substitution protocols. Previous studies have estimated a far greater cost
      differential based on unrealistic labor estimates. We found that supervision of
      patients using MDIs minimized the differential cost between WN and MDI therapy
      and that cost savings are maximal in patients who can self-administer MDI
      therapy. Methodologically sound economic evaluations can better identify true
      cost savings and variables that need further study.

PMID- 8862105
TI  - Epidemiology and outcome of Pseudomonas aeruginosa bacteremia, with special
      emphasis on the influence of antibiotic treatment. Analysis of 189 episodes.
AB  - OBJECTIVE: To evaluate the trend in incidence of Pseudomonas aeruginosa
      bacteremia, underlying conditions of patients, mortality rate, and factors
      associated with poor outcome. PATIENTS AND METHODS: Medical charts of 189
      consecutive episodes of P aeruginosa bacteremia, detected between January 1,
      1991, and December 31, 1994, were prospectively evaluated. Associated risk
      factors, treatment, and outcome were recorded. RESULTS: Pseudomonas aeruginosa
      bacteremia represented 5.7% of the total number of bacteremias, 6.9% of
      nosocomial bacteremias, and 23.6% of nosocomial gram-negative bacteremias. There
      were 1.5 episodes per 1000 discharges. These numbers were slightly lower than
      those recorded at our hospital 10 years earlier. Human immunodeficiency virus
      infection was the most frequent underlying disease (28/189 [15%]). Overall
      mortality was 18% (34/189). The presence of fatal underlying disease (P < .001),
      surgery (P = .001), pneumonia (P = .02), and severe sepsis (P < .001) were
      associated with poor prognosis, the mortality of the patients with these
      variables being 28%, 28%, 47%, and 62%, respectively. The presence of
      inappropriate definitive antimicrobial treatment became an independent factor
      predictive of death (P = .04) only when the subset of patients with intravenous
      catheter-associated bacteremia was excluded from the analysis. The survival rate
      was no greater in patients who received 2 or more antibiotics active in vitro
      against P aeruginosa than in those who received only 1. Neutropenia was not
      associated with increased mortality. The use of colony-stimulating factors did
      not affect the outcome of the neutropenic patients. CONCLUSIONS: The rate of P
      aeruginosa bacteremia is falling slightly at our hospital. The emergence of the
      human immunodeficiency virus epidemic has had a considerable impact on both
      epidemiology and mortality. The presence of severe underlying disease, surgery,
      pneumonia, and, especially, severe sepsis are associated with a poor outcome.
      With the exclusion of patients with intravenous catheter-associated P aeruginosa
      bacteremia, the administration of an appropriate antimicrobial therapy is
      essential to a good outcome. Treatment with 1 active antibiotic seems to be
      sufficient.

PMID- 8862106
TI  - A multi-institutional study of care given to patients dying in hospitals. Ethical
      and practice implications.
AB  - BACKGROUND: Relatively little attention has been paid to how physicians care for
      dying patients once an initial decision to forgo life-sustaining treatment is
      made. OBJECTIVES: To describe characteristics of patients forgoing treatment,
      determine the range and sequential process of forgoing treatment, and suggest
      ethical and practice implications. METHODS: Charts of 75 consecutive patients
      dying at each of 4 hospitals were reviewed for this case series. Two hundred
      ninety-one (98%) of 297 charts were available for review; 274 patients died in
      acute care beds and are included in this study. Data collected included patients'
      diagnoses, mental statuses, lengths of stay, timing of the first decision to
      forgo treatment, and range and sequence of interventions forgone. MAIN OUTCOME
      MEASURES: Proportion forgoing life-sustaining treatment, number of interventions
      forgone and decision times per patient, and ranked order of treatment withdrawal.
      RESULTS: Two hundred twenty-nine (84%) of 274 patients who died had some
      intervention forgone before death. Only 35% of patients forgoing life-sustaining
      treatment were able to participate in decision making. On average, 3.8
      interventions were forgone per patient. Resuscitation and/or intubation were
      generally the first measures withheld; once a patient required ventilatory
      support, withdrawing ventilatory support was a late decision. CONCLUSIONS: The
      majority of patients dying at these institutions did so after decisions to limit
      treatment, but few patients were able to participate in these decisions. Forgoing
      life-sustaining treatment generally occurred in a sequential manner over several
      days; the rationale for this stepwise retreat is not, however, clinically or
      ethically obvious.

PMID- 8862107
TI  - Tularemia presenting as community-acquired pneumonia. Implications in the era of
      managed care.
AB  - A case of pleuropulmonary tularemia was diagnosed by sputum culture and serologic
      studies in a patient who did not have classic epidemiological risks for
      tularemia. The patient had atypical pneumonia when initially seen and his
      condition slowly improved with antibiotic therapy that included erythromycin
      lactobionate. The diagnosis of tularemia was delayed because the gram-negative
      rod isolated from the patient's sputum was initially not speciated in an effort
      to reduce laboratory costs.

PMID- 8862108
TI  - Prosthetic valve endocarditis due to Streptococcus pneumoniae.

PMID- 8862109
TI  - Recent antipsychotic regulations in long-term care.

PMID- 8862110
TI  - Working memory in temporal lobe epilepsy: an event-related potential study.
AB  - Event-related potentials (ERPs) were recorded to a digit-probe identification and
      matching task (modified 'Sternberg paradigm') in 29 patients with temporal lobe
      epilepsy (TLE) and 26 healthy subjects. Our main aim was to identify the
      neurophysiological correlates of abnormal short term memory function in patients
      with TLE. Neuropsychological tests allowed the definition and comparison of two
      patient groups according to the presence or absence of memory dysfunction. These
      two groups did not differ significantly in mean age, education years, IQ, seizure
      duration, seizure frequency, anti-epileptic drug (AED) regimes, or on findings on
      neuroimaging. ERPs recorded under different levels of memory load were analysed
      both by conventional component identification and by an objective computer method
      of determining mean amplitudes of multiple 50 ms epochs (MMA analysis). We found
      that some significant abnormalities were common to both groups of patients; these
      included slow reaction times, a reduced amplitude of the N170 wave (and the
      corresponding 157-210 ms epoch in the MMA analysis) and a broad late negative
      shift between 577 and 735 ms. Other findings, including a significantly reduced
      performance accuracy as the level of memory load increased, were restricted to
      patients with abnormal memory function. The ERP changes that were specific to
      these patients occurred within a latency band of 200-420 ms and included a
      relatively preserved, but delayed P250 component and a delayed and attenuated
      N290 wave. When compared with either healthy subjects or with patients with
      normal memory, the responses in patients with abnormal memory showed an abnormal
      'positive shift' between 262 and 315 ms after probe presentation and a further
      positive shift between 315 and 420 ms as memory load increased. These
      abnormalities of 'memory scanning' ERPs in patients with TLE which paralleled
      neuropsychological and behavioural evidence of memory dysfunction, and which
      occurred in the section of the response that is sensitive to memory loading in
      healthy subjects, provide further objective evidence that abnormalities of short
      term memory processes contribute to the memory deficits of TLE.

PMID- 8862111
TI  - Use of non-linear EEG measures to characterize EEG changes during mental
      activity.
AB  - Non-linear EEG analysis provides a possibility for studying the dynamical changes
      in cortical networks related to mental activity. In this study the correlation
      dimension D2 was used to study local changes in complexity, and the mutual
      dimension Dm was used to assess changes in the dynamical coupling between
      different brain areas. EEGs were recorded in 25 healthy subjects under three
      conditions: (1) eyes closed, (2) eyes open, and (3) mental arithmetic with eyes
      closed (serial subtraction of 7s from 1000). In the eyes-closed condition, D2 was
      lower at parieto-occipital sites. D2 increased during the eye-open and arithmetic
      conditions. Contrary to the D2, the Dm showed no regional differences in the eyes
      closed condition. A clear increase in Dm was seen during eyes open and
      arithmetic. We conclude that both the correlation dimension and the mutual
      dimension are very sensitive to EEG changes during simple visual information
      processing and during mental arithmetic. However, these measures seem to be
      relatively non-specific, and correlate only weakly with performance on the
      arithmetic task.

PMID- 8862112
TI  - The N2pc component as an indicator of attentional selectivity.
AB  - Event-related potentials (ERPs) were recorded during visual discrimination tasks
      in which stimulus arrays were presented that contained one lateral target and 3
      (experiment 1) or one (experiments 2 and 3) non-targets. In experiments 1 and 2,
      targets differed from non-targets with respect to their form or their color. In
      experiment 3, word pairs were presented, with targets differing from non-targets
      with respect to their content. Subjects were required to respond to the identity
      of the target. In all experiments, an enhanced negativity was elicited at
      posterior electrodes contralateral to the location of the target. In the form
      discrimination tasks, this effect was present in the N1, N2, and P3 time
      intervals. In the color discrimination tasks, it was confined to the N2 time
      range. In the word discrimination task (experiment 3), this effect could only be
      observed over the left posterior hemisphere. It is argued that these lateralized
      negativities reflect the N2pc component that is assumed to indicate attentional
      filtering processes during visual search tasks. The present results extend this
      assumption by showing that this component is also elicited when targets are
      presented together with just one non-target item. It is argued that the N2pc may
      reflect the attentional selection of task-relevant stimuli.

PMID- 8862113
TI  - N400 evidence of abnormal responses to speech in Alzheimer's disease.
AB  - The status of semantic priming in Alzheimer's disease (AD) was examined using the
      speech elicited N400 component of the event-related brain potential (ERP). Speech
      was naturally paced, with 1 s of silence before the final word. In the semantic
      task, subjects attended to the meaning of the sentences for a subsequent memory
      test. In the phonemic monitoring task, they counted the words beginning with the
      letter 'p'. The effects of age were assessed by comparing young and elderly, and
      the effects of disease by comparing elderly and AD subjects. In healthy young and
      elderly subjects, N400s were large to semantically unprimed words and small to
      semantically primed words. In AD subjects, N400s were large to primed words,
      reflecting a failure of the sentence stem to prime the final word, and probably
      an impairment in semantic knowledge. The N400 priming effect was not smaller
      during the phonemic than semantic task in any group, suggesting that the semantic
      qualities of speech are processed even when subjects are attending to phonemic
      qualities. N400 latency was delayed with age and further delayed with dementia.

PMID- 8862114
TI  - Sensory processing during early and late nocturnal sleep.
AB  - The present experiments in 10 healthy men compared auditory evoked potentials
      (AEPs) and heart rate (HR) indicators of stimulus processing during early and
      late phases of nocturnal stage 2 sleep. Definition of early and late sleep relied
      on endocrine pituitary-adrenal secretory activity which is known to be inhibited
      during early nocturnal sleep but sharply increases during late sleep. AEPs and HR
      responses were recorded to trains of 10 tone pips (1000 Hz; interstimulus
      interval 15 s; intertrain interval > 3 min). On one night, tone pips were
      presented in the first part of sleep, on the other night tone presentation took
      place in the second part, with the order of conditions balanced across subjects.
      Amplitudes of N150 and N550 components of the AEP, and of acceleratory and
      deceleratory HR responses, were higher during the first than second part of
      nocturnal sleep (P < 0.05). Moreover, habituation of P240 and N550 amplitudes was
      slower during the first than second part of sleep (P < 0.05). In supplementary
      experiments, AEP and HR responses to the same stimuli did not differ between the
      first and second part of the night when subjects were waking during stimulation.
      Results indicate a reduced inhibitory control over cortical stimulus processing
      during early nocturnal sleep. This diminished inhibition of cortical processing
      together with other concomitant changes during early sleep (such as the enhanced
      inhibition of pituitary-adrenal secretion) may reflect a coordinated regulatory
      function of sleep possibly mediated by hippocampal mechanisms.

PMID- 8862115
TI  - Automated seizure detection using a self-organizing neural network.
AB  - An algorithm for automated seizure detection using the self-organizing map (SOM)
      neural network (NN), with unsupervised training, was used to detect seizures in
      24 long-term EEG recordings. The detection paradigm was tested on a constant 8
      channel subset of 18 channel scalp EEG recordings. The NN was trained to
      recognize seizures using 98 training examples. A strategy was devised using
      wavelet transform to construct a filter that was 'matched' to the frequency
      features of examples used to train the NN. Four second epochs of training
      examples and EEGs being tested were transformed into time-independent
      representations of spectrograms resulting in a time-frequency representation of
      the time-series. Rule-based long and short term contextual features were used for
      detection in association with the NN. Fifty-six seizures were detected from a
      possible 62 (90%) associated with an average 0.71 +/- 0.79 false-positive errors
      per hour using the same 'population' detection parameters. When the sensitivity
      for detection was increased, all but one of the 62 seizures were detected (98%).
      Less than 1.0 false-positive error per hour occurred in all but 5 records when
      using the 'population' parameters. The combination of rule-based detection
      criteria employing contextual parameters and unsupervised training of NNs to
      recognize time-frequency patterns is a promising direction for automated seizure
      detection.

PMID- 8862116
TI  - Effects of carbamazepine on cortical excitatory and inhibitory phenomena: a study
      with paired transcranial magnetic stimulation.
AB  - The effect of a single dose of oral carbamazepine on cortical facilitatory and
      inhibitory phenomena was investigated in 13 healthy human subjects by focal
      transcranial magnetic stimulation. Paired stimulation was performed via a figure
      of-eight shaped magnetic coil using two Magstim-200 stimulators and a Bistim
      interface at interstimulus intervals of 3, 10, and 17 ms. In addition, the silent
      period evoked by single focal transcranial stimuli during sustained voluntary
      muscle contraction was investigated without and with carbamazepine. Recordings of
      compound muscle action potentials (CMAP) were taken from the left first dorsal
      interosseus muscle. Carbamazepine significantly reduced the facilitatory effect
      of conditioning stimuli of 85% of motor threshold at an interstimulus interval of
      10 ms on the CMAP-amplitude from 162% to 127%, whereas under all other conditions
      no significant depression of CMAP-amplitudes occurred. This effect is discussed
      in the context of carbamazepine's use-dependent inhibition of neuronal high
      frequency discharges. The mean relative duration of the silent period was longer
      with carbamazepine at all 6 stimulus intensities investigated, the absolute
      effect being very low in relation to the interindividual variability of silent
      period duration. The study demonstrates the applicability of transcranial
      magnetic stimulation as an in vivo method in the assessment of drug effects on
      cortical facilitatory as well as inhibitory phenomena.

PMID- 8862117
TI  - Movement-related slow cortical magnetic fields and changes of spontaneous MEG-
      and EEG-brain rhythms.
AB  - Cortical activity was recorded from 5 healthy adults with a 122-channel whole
      head magnetometer while the subjects performed during unilateral finger movements
      at self-paced intervals exceeding 6 s. The readiness field (RF) started over the
      contralateral somatomotor area 0.3-1 s prior to the movement onset in subjects
      (Ss) 1, 2, and 4, and culminated in the motor field (MF) 30 ms after it (Ss 1-4).
      These signals were followed by movement evoked fields MEFI (Ss 1-5) and MEFII (Ss
      1-4) at 100-150 ms and 200-250 ms after the movement onset, respectively. One
      subject showed clear RF over the ipsilateral hemisphere as well. The
      contralateral dominance of the RF contrasted the more symmetric distribution of
      the simultaneously recorded electric Bereitschaftspotential (BP). The RF onset
      never preceded the BP onset. We suggest that BP receives contribution from the
      early bilateral activation of the crown of the precentral gyrus, whereas RF
      reflects later activity of the fissural motor cortex. Spontaneous oscillations in
      the background activity (spontaneous activity) of approximately 10 Hz started to
      dampen 2-3 s prior to the movement onset in the somatomotor areas of both
      hemispheres with contralateral predominance (S1 and S3), and returned to a steady
      level 0.8-2 s after the movement onset in all subjects. Higher frequency bands in
      the same area displayed a prominent rebound about 1 s after the movement onset in
      4 subjects. Execution of self-paced movements is evidently expressed differently
      in the slow movement-related fields and in the cortical spontaneous activity.

PMID- 8862118
TI  - Special types of periodic lateralized epileptiform discharges associated with
      confusional state in cerebral circulation insufficiency.
AB  - A peculiar type of periodic lateralized epileptiform discharges (PLEDs) was
      recorded on 22 EEGs performed in 11 patients. They were characterized by bursts
      of sinusoid activity around 7-9 Hz, usually followed by a slow wave, lasting less
      than 500 ms, with a period less than 2 s, and these sequences could be continuous
      over several days. We propose to name this pattern 'periodic sinusoid paroxysmal
      activity' (PSPA). PSPA was recorded mainly over both parieto-temporo-occipital
      regions, although asymetrically. Sensory stimulations and anticonvulsants had no
      effect on PSPA. In three cases, mobilization of the head blocked PSPA. The
      spontaneous disappearance of PSPA was sometimes followed by classical PLEDs. PSPA
      was always associated with a confusional state and behavioural disturbances, and
      erratic distal clonic movements were seen in 6 cases. These symptoms disappeared
      as soon as PSPA ceased. Patients had either vascular risk factors or a previous
      cerebrovascular insult. The confusional state was associated with either lowered
      carotidian bloodflow or probable global cerebral hypoperfusion due to a systemic
      pathology. A vascular origin of PSPA is likely, due to the presence of vascular
      risk factors, to the morphology of PSPA and to the provoking and inhibiting
      factors.

PMID- 8862119
TI  - Pathogenesis and treatment of ascites.

PMID- 8862120
TI  - C-peptide revisited--new physiological effects and therapeutic implications.
AB  - Recent studies have demonstrated that replacement of C-peptide to normal
      physiological concentrations in insulin-dependent diabetic (IDDM) patients on a
      short-term basis (1-3 h) results in decreased glomerular hyperfiltration,
      augmented glucose utilization and improved autonomic nervous function. More
      prolonged administration (1-3 months) of C-peptide to IDDM patients is
      accompanied by improvements in both renal and autonomic nervous function.
      Moreover, both in-vitro and in-vivo studies indicate that C-peptide may have a
      role in the regulation of insulin secretion. The effects of C-peptide may in part
      be explained by its ability to stimulate Na+,K(+)-ATPase activity. In conclusion,
      the combined findings indicate that C-peptide is a biologically active hormone.
      The possibility that C-peptide therapy in IDDM patients may be beneficial should
      be considered.

PMID- 8862121
TI  - Population-based erythrocyte sedimentation rates in 3910 subjectively healthy
      Norwegian adults. A statistical study based on men and women from the Oslo area.
AB  - OBJECTIVES: To establish age- and sex-specific reference limits for the
      erythrocyte sedimentation rate (ESR) in asymptomatic Norwegian adults. DESIGN:
      Single ESR recordings were obtained by the classical or a modified Westergren
      method from 2145 men and 1765 women (93% being blood donors) with age range 20-90
      years, and analysed statistically. RESULTS: There was a significant positive
      association between ESR level and age, consistent with a parabolic pattern in men
      but a linear one in women. The mean values for men were about 3 mm h-1 at 20
      years, 6 mm h-1 at 55 years, and 10 mm h-1 at 90 years, and 6, 9, and 11 mm h-1
      respectively for women. These averages (predicted by regression lines) were
      significantly higher in women up to the age of 75 years, after which the
      estimated sex-specific 95% confidence limits for mean values were found to
      overlap. CONCLUSIONS: The upper reference levels expected to be exceeded only by
      chance in 5% of single individual recordings at the ages of 20, 55 or 90 years,
      respectively, were estimated to be 12, 14 and 19 mm h-1 for men, and 18, 21 and
      23 mm h-1 for women. Higher values should be controlled and, if confirmed, lead
      to a clinical check-up. However, about 76% of our overall material had ESR values
      lower than 9 mm h-1. Knowledge of each person's baseline ESR value might increase
      the disease-predictive ability of the test. If several measurements over years
      reveal a steeper rise with age than depicted in our population-based curves, it
      should be taken seriously, even when each reading is below the population-based
      reference limits.

PMID- 8862122
TI  - Rising erythrocyte sedimentation rate during several years before diagnosis can
      be a predictive factor in 70% of renal cell carcinoma patients. The benefit of
      knowing subject-based reference values.
AB  - OBJECTIVES: A diagnosis of renal cell carcinoma (RCC) early enough for
      potentially curative surgery is difficult. We wanted to establish whether the
      erythrocyte sedimentation rate (ESR) in RCC patients had begun to rise before the
      appearance of any symptoms or signs and, if so, when. DESIGN: A retrospective
      study of the evolution of the ESR in 236 randomly selected RCC patients during
      several years before diagnosis, comparing the results with previously obtained
      population-based control values. RESULTS: It is generally held that RCC patients
      have a high ESR at diagnosis. In our material, however, 29.7% of the RCC cases
      had an ESR that at this time was at or below the population-based upper reference
      limit; it had not increased significantly, neither with time before diagnosis,
      nor with age. In 70.3% of RCC patients the ESR was increased and had been
      significantly rising for up to 6 years or more before diagnosis. This had not
      been adequately responded to, probably because the physicians lacked knowledge of
      the patients' baseline ESR, and because none of the prediagnostic readings had
      been above the population-based reference limit. CONCLUSIONS: Systematic ESR
      graphic recordings over time will enable a physician to determine each
      individual's baseline value, and hence note any continuously rising trend, which
      should lead to further investigations, e.g. an ultrasound kidney examination.
      This may provide an early clue to many otherwise non-symptomatic RCC cases. It is
      time for a reappraisal of the predictive value of the ESR to discover early RCC,
      and possibly other diseases as well.

PMID- 8862123
TI  - Exploring the declining case fatality in acute stroke. Population-based
      observations in the northern Sweden MONICA Project.
AB  - OBJECTIVES: Declining case fatality in acute stroke has been reported from many
      western countries. The aim of this study was to explore in what subset of
      patients the decline in case fatality has occurred. SETTING: In a population
      based study, acute stroke events were recorded in the age group 25-74 years in
      northern Sweden during the years 1985-1993 within the framework of the WHO MONICA
      Project. SUBJECTS: In total 3486 men and 2212 women with a first-ever stroke
      (except subarachnoid haemorrhage) were included. MAIN OUTCOME: Change in stroke
      incidence, case fatality and neurological deficits at onset over a 9-year period.
      RESULTS: The incidence (first-ever stroke) did not change over the years, while
      the overall case fatality decreased from 18.2% in 1985-1987 to 13.5% in 1991
      1993. In both men and women with non-haemorrhagic stroke, a trend was seen
      towards an increasing incidence of mild stroke events over the years. In both
      sexes, a significant decline in case fatality was seen in patients with minor
      deficits at onset, while no change in case fatality was seen in patients with
      extensive deficits. There was no change in incidence of intracerebral
      haemorrhage, but the case fatality in patients with intracerebral haemorrhage
      declined significantly from 36% to 29% during the study period. CONCLUSIONS: A
      declining case fatality was observed in both men and women. Among patients with
      non-haemorrhagic stroke, the decline was confined to patients with minor
      deficits. The declining case fatality can be attributed both to a shift in the
      severity towards more patients presenting with mild symptoms, and an improved
      prognosis in patients with minor deficits at onset, probably because of improved
      medical management.

PMID- 8862124
TI  - Dissociation between urinary albumin excretion and variables associated with
      insulin resistance in a healthy population.
AB  - OBJECTIVES: To see if the cluster of metabolic and haemodynamic variables defined
      as comprising Syndrome X varied as a function of urinary albumin excretion (UAE)
      rate in a healthy population. DESIGN: A cross-sectional, population-based study.
      SETTING: A factory in Italy. SUBJECTS: Two hundred and twenty-five healthy
      volunteers, 115 men and 110 women. OUTCOME MEASURES. Measurements were made of
      the plasma glucose and insulin responses to oral glucose, fasting triglyceride
      (TG) and high density lipoprotein (HDL)-cholesterol concentrations, blood
      pressure, and UAE rates. RESULTS: Only five of the 225 volunteers had micro
      albuminuria, defined as a UAE rate > 2 micrograms min-1, and the UAE rate was < 5
      micrograms min-1 in 80% of the volunteers. Significant variations in the
      metabolic and haemodynamic variables measured were not associated with any
      differences in UAE. Finally, significant relationships were found between various
      measures of plasma insulin concentration and plasma glucose response to oral
      glucose, plasma TG and HDL-cholesterol concentrations, and mean arterial blood
      pressure, independent of variations in age, body mass index, ratio of waist-to
      hip girth, and UAE rates. CONCLUSION: The widespread variability in plasma
      glucose and insulin responses, plasma TG and HDL-cholesterol concentrations, and
      blood pressure that are seen in the population at large cannot be attributed to
      variations in UAE rate.

PMID- 8862125
TI  - Glomerular lipid deposition and proteinuria in a patient with familial
      dysbetalipoproteinaemia.
AB  - This report describes a male patient who was found to have proteinuria at age 31.
      Renal biopsy showed glomerular hypercellularity with enlarged, lipid-filled
      endocapillary cells. On subsequent lipid analysis there was elevation of
      cholesterol and triglyceride, with apolipoprotein E genotype E2/E2. The clinical
      course was complicated by pancreatitis and onset of diabetes. After treatment
      with gemfibrozil and some improvement of the lipid profile, a second renal biopsy
      showed marked reduction of the glomerular foam cells, despite an increased level
      of proteinuria. This case emphasizes the potential role that lipid abnormalities
      may play in renal dysfunction.

PMID- 8862126
TI  - Cobalamin deficiency with megaloblastic anaemia in one patient under long-term
      omeprazole therapy.
AB  - The first case of cobalamin deficiency with megaloblastic anaemia in a patient
      under long-term omeprazole therapy is presented. This patient received omeprazole
      at a daily dose of 40-60 mg for 4 years as treatment for a gastro-oesophagal
      reflux complicated by peptic oesophagitis. Seric vitamin B12 was dramatically
      decreased at 80 pmol L-1. The Schilling test was normal (13%) with crystalline
      [57Co] cobalamin and it was at 0% with [57Co] cobalamin-labelled trout meat. All
      other assimilation tests were normal except an expiratory hydrogen breath test
      performed with lactulose. The haematological status was restored after
      intramuscular treatment with cobalamin. In conclusion, prolonged omeprazole
      therapy can be responsible for a cobalamin deficiency due to protein-bound
      cobalamin malabsorption.

PMID- 8862127
TI  - Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25
      dihydroxy vitamin D.
AB  - We report a case of a female patient with sarcoidosis who presented with a
      generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis.
      Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with
      a normal plasma 1,25-dihydroxy vitamin D concentration occurred later.
      Corticosteroid therapy resulted in prompt clinical and biochemical responses with
      normalization of plasma calcium and a significant reduction in 1,25-dihydroxy
      vitamin D concentration. This is an exceptional presentation of sarcoidosis with
      severe hypercalcaemia and normal vitamin D metabolites.

PMID- 8862128
TI  - Autoantibodies to peripheral nerve glycosphingolipids SPG, SLPG, and SGPG in
      Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy.
AB  - Unlike CNS myelin, human peripheral nerve myelin has the acidic
      glycosphingolipids sialosyl paragloboside (SPG), sialosyl lactosaminyl
      paragloboside (SLPG), and sulfated glucuronyl paragloboside (SGPG). To elucidate
      the pathogenesis of Guillain-Barre syndrome (GBS) and chronic inflammatory
      demyelinating neuropathy (CIDP), we investigated the autoantibodies to peripheral
      nerve molecules in patients with these diseases and compared the frequency of the
      autoantibodies with that of autoantibody to GM1 which is present in both the CNS
      and PNS. The report of Sheikh et al. (Ann. Neurol. 1995; 38: 350) that
      Campylobacter jejuni bears the SGPG epitope led us to study whether sera from
      patients with GBS subsequent to C. jejuni enteritis have anti-SGPG antibody; but,
      high anti-SGPG antibody titers were not found in the GBS patients from whom C.
      jejuni was isolated. Although the frequency of the anti-SPG, anti-SLPG and anti
      SGPG antibodies were lower than that of the anti-GM1 antibody in GBS, 5 patients
      with demyelinating GBS had high IgG anti-SPG antibody titers. IgG anti-SPG
      antibody may function in the development of demyelinating GBS. We found that 6
      CIDP patients had elevated IgM anti-SGPG antibody titers. Immunoelectrophoresis
      failed to detect IgM M-protein in 3 of the patients. IgM anti-SGPG antibody could
      be a diagnostic marker for a subgroup of CIDP with or without paraprotein.

PMID- 8862129
TI  - Stereoselective inhibition of natural killer activity by the sigma ligand (+)
      pentazocine.
AB  - The effect of sigma (sigma) receptor ligands on natural killer (NK) activity was
      examined both in vivo and in vitro. Following injection of mice with sigma
      receptor ligands such as (+)-pentazocine, (-)-pentazocine, BD 1073, BD 1165 and
      BD 737, NK activity was measured in poly-I.C.-stimulated mouse splenocytes. (+)
      Pentazocine reduced NK cell activity in a dose-dependent fashion, while the (-)
      enantiomer was inactive in this measure. For example, at a dose of 50 mg/kg, (+)
      pentazocine suppressed NK activity (using effector to target cell ratios of
      200:1, 100:1 and 50:1) by > 70%, 24 h after injection while (-)-pentazocine was
      inactive. The other sigma ligands examined either slightly enhanced or had no
      effect on NK activity. Nonetheless, parenteral administration of the sigma
      receptor ligand BD 1165 blocked (+)-pentazocine-induced suppression of NK
      activity, while the opiate receptor antagonist naltrexone was ineffective.
      Addition of sigma receptor ligands (10(-11)-10(-5) M) to splenocyte cultures for
      24 h did not affect NK activity. These findings indicate that while sigma
      receptor ligands are capable of modulating NK activity, this effect is not the
      result of an action on splenocyte sigma receptors, but may be mediated via sigma
      receptors either in the central or peripheral nervous systems.

PMID- 8862130
TI  - Preferential association of V lambda x light chains with gamma 2a heavy chains in
      naturally occurring human myelin basic protein reactive antibodies.
AB  - Active immunization with myelin basic protein (MBP) induces experimental allergic
      encephalomyelitis (EAE) in a variety of animal species, including rats and mice.
      We have previously described the ability of the newly described mouse lambda
      (lambda) variable (V) region V lambda x, to confer MBP reactivity to an Ab. In
      this report, we have evaluated the heavy (H) chain isotype distribution of V
      lambda x-bearing Abs in normal mouse serum. We demonstrate a biased H chain
      isotype association with V lambda x light (L) chains with a skewing towards gamma
      2a and 2b isotypes. The IgG2a restriction in normal mouse Igs is even more
      evident in V lambda x-containing Abs that bind MBP. This was confirmed by the
      ability of purified polyclonal IgG2a Abs to bind MBP and the finding that most or
      all of the IgG2a Abs that bind MBP seem to harbor a V lambda x L chain. The
      specificity of naturally-occurring V lambda x-bearing Abs with MBP can be
      localized to a particular epitope encompassing residues 25-34 of the MBP
      molecule. Furthermore, virtually all of the reactivity of V lambda x-containing
      Abs with MBP peptide 25-34 is associated with the gamma 2a isotype. Collectively,
      these results suggest that the interaction of V lambda x with MBP seems to be
      facilitated by an association with gamma 2a which may reflect preferred VH usage
      by this isotype. Such unique pairing of particular H chains with V lambda x L
      chains in Abs that bind MBP may be indicative of a new B-cell component involved
      in the pathogenesis of EAE.

PMID- 8862131
TI  - Differential effects of transforming growth factor-beta 1 on interleukin-1
      induced cellular inflammation and vascular permeability in the rabbit retina.
AB  - Intra-vitreal injection of 300 U of interleukin (IL)-1 beta into the rabbit eye
      induces an inflammation of the retina characterized by hemorrhage, monocyte and
      neutrophil infiltration, and an increase in vascular permeability that peaks 24 h
      post-injection. Since the epiretinal vessels involved in this inflammation form
      part of the blood-retina barrier, we used this model to investigate the effects
      of the immunosuppressive cytokine TGF beta 1 on inflammation within the context
      of the central nervous system. We found that intra-vitreal injection of 1
      microgram rh TGF beta administered concomitantly with rh IL-1 beta significantly
      reduced IL-1 beta-induced hemorrhage by 78%, and monocyte and neutrophil
      infiltration by 53% and 62%, respectively. In contrast, TGF beta did not reduce
      the IL-1 beta-induced increase in vascular permeability. However, TGF beta by
      itself caused a statistically significant increase in serum proteins in perfused
      tissues of the eye, to give a 3.1 +/- 0.4 fold increase in protein content over
      control values. No cellular inflammation accompanied this alteration in vascular
      permeability. These data indicate that whereas the local administration of TGF
      beta may be an effective inhibitor of cellular inflammation in the CNS, the
      effects on alterations in vascular permeability and accumulation of serum
      proteins may be more complex.

PMID- 8862132
TI  - Methylprednisolone attenuates interferon-beta induced expression of HLA-DR on
      monocytes.
AB  - The effect of methylprednisolone on constitutive and interferon-beta (IFN-beta)
      induced HLA-DR expression on monocytes from multiple sclerosis (MS) patients was
      investigated. Constitutive HLA-DR expression was reduced by 50% following a
      single dose (500 mg) of intravenous methylprednisolone (IVMP). Stimulation with
      natural IFN-beta, in vitro, resulted in a 20 fold increase in HLA-DR expression.
      Following IVMP, IFN-beta inducible HLA-DR levels were reduced (non-significantly)
      by 20-30%. Experiments in which monocytes from normal subjects and MS patients
      were pre-treated in vitro with methylprednisolone prior to IFN-beta stimulation
      revealed that induction of HLA-DR was significantly inhibited; in contrast, IFN
      beta induced HLA-DR expression was not down-regulated following subsequent in
      vitro treatment with methylprednisolone. These findings suggest that the
      immunomodulatory effects of IVMP could be attenuated in MS patients receiving
      regular IFN-beta therapy.

PMID- 8862133
TI  - Angiogenic and inflammatory responses following skeletal muscle injury are
      altered by immune neutralization of endogenous basic fibroblast growth factor,
      insulin-like growth factor-1 and transforming growth factor-beta 1.
AB  - Injured skeletal muscle degeneration comprises early microvascular changes and
      inflammatory cell infiltration, possibly under the control of several growth
      factors. We have studied the role of basic fibroblast growth factor (bFGF),
      insulin-like growth factor-1 (IGF1), and transforming growth factor beta-1 (TGF
      beta 1), by injecting specific anti-growth factor neutralizing antibodies into
      mouse extensor digitorum longus muscle at the time of injury (denervation and
      devascularization). Four days later, at the height of damaged myofiber
      phagocytosis, we assessed quantitatively revascularization, phagocytic activity,
      and inflammation. The immune neutralization of bFGF reduced the number of
      capillaries, macrophages and mast cells, and delayed necrotic myofiber
      phagocytosis. The immune neutralization of IGF1 or TFG beta 1 promoted muscle
      revascularization, macrophage infiltration and necrotic myofiber phagocytosis.
      While IGF1 neutralization reduced the number of mast cells and did not modify
      that of T-cells or neutrophils, TGF beta 1 neutralization increased the number of
      all of these cells. This study strongly suggests differing roles for bFGF, IGF1
      and TFG beta 1 in angiogenic and inflammatory responses during muscle
      degeneration, apart from their known effects on the behaviour of myogenic cells.

PMID- 8862134
TI  - Localization of mRNA for leukemia inhibitory factor receptor in the adult rat
      brain.
AB  - The distribution of leukemia inhibitory factor receptor (LIFR) mRNA in the adult
      rat brain was examined by in situ hybridization technique. The intense signals of
      LIFR mRNA were restricted to specific brain regions relevant to the motor and
      sensory systems. The moderate expression of LIFR mRNA was observed in several
      brain regions, including the cerebral cortex, hippocampus, thalamus, hypothalamus
      and cerebellum. Most of the signals of LIFR mRNA were detected on likely neuronal
      cells. These findings suggest the possibility that LIF has potential actions on
      the neuronal cells in the central nervous system of the adult rat.

PMID- 8862135
TI  - Changes in noradrenergic sensitivity to tumor necrosis factor-alpha in brains of
      rats administered clonidine.
AB  - Tumor necrosis factor-alpha (TNF alpha) and the imidazoline clonidine modulate
      norepinephrine (NE) release from noradrenergic nerve terminals in the central
      nervous system. The present study demonstrates an intrinsic association between
      presynaptic alpha 2-adrenergic receptor sensitivity and TNF alpha responsiveness
      in governing this NE release. Superfusion and electrical field stimulation were
      applied to a series of rat hippocampal brain slices in order to study the
      regulation of [3H]-NE release. The alpha 2-adrenergic agonist clonidine and the
      cytokine TNF alpha concentration-dependently inhibit [3H]-NE release; whereas,
      the alpha 2-adrenergic antagonist idazoxan potentiates [3H]-NE release. The
      fractional release of [3H]-NE during field stimulation of control hippocampal
      slices was decreased by the addition of TNF alpha in a concentration-dependent
      manner, an effect which was potentiated by the alpha 2-adrenergic antagonist
      idazoxan; whereas, TNF alpha attenuated the concentration-dependent potentiating
      effect of idazoxan. Furthermore, constitutive TNF alpha, demonstrated to be
      present in several brain areas, was significantly decreased following
      administration of the alpha 2-adrenergic agonist clonidine (0.6 mg/kg, i.p.,
      twice daily) to rats for either 1 or 14 days, without a change in TNF alpha mRNA
      accumulation. We next investigated whether the presynaptic sensitivity to TNF
      alpha was changed after clonidine administration to rats. TNF alpha enhanced,
      rather than inhibited, [3H]-NE release after 1 day of clonidine administration,
      while a suppressed sensitivity to TNF alpha was observed in the hippocampus after
      14 days of clonidine administration. In addition, in the presence of idazoxan,
      TNF alpha potentiation of [3H]-NE release after 1 day clonidine administration
      was reversed to a decreased inhibition as compared to control slices exposed to
      idazoxan. Therefore, the temporary reversal in the presynaptic TNF alpha response
      after 1 day of clonidine administration illustrates a mechanism of action for its
      persistent antihypertensive effect, its transient sedative and antihyperpathic
      effects, and its acute ability to promote antidepressants. These results
      demonstrate a novel role for an immune mediator in the central nervous system,
      and demonstrates that presynaptic TNF alpha responsiveness is intimately
      associated with adrenergic receptor sensitivity.

PMID- 8862136
TI  - A study of human T-cell lines generated from multiple sclerosis patients and
      controls by stimulation with peptides of myelin basic protein.
AB  - We generated T-cell lines from the peripheral blood of controls and of patients
      with multiple sclerosis (MS) by stimulation with overlapping synthetic peptides
      representing the entire sequences of all four isoforms of human myelin basic
      protein (MBP). The T-cell lines reacted to a wide range of epitopes in the major
      isoforms of MBP and to epitopes that were present only in the minor isoforms.
      Many MS patients and controls had T-cells responding to one or more cryptic MBP
      epitopes, as indicated by the generation of a peptide-specific T-cell line(s) by
      stimulation with synthetic peptides but not by stimulation with whole MBP. About
      one-third of the peptide-generated lines were cytotoxic. Although we have shown
      that this technique of peptide stimulation is effective in generating human
      antiviral cytotoxic CD8+ T-cell lines, all the cytotoxic MBP-specific lines
      generated by this method were predominantly CD4+. Our study did not reveal any
      significant differences, between MS patients and controls, in reactivity to
      epitopes within any of the isoforms of MBP.

PMID- 8862137
TI  - Vascular cell adhesion molecule-1 mRNA is expressed in immune-mediated and
      ischemic injury of the rat nervous system.
AB  - In this study we used nonradioactive in situ hybridization for the cellular
      localization of vascular cell adhesion molecule-1 (VCAM-1) mRNA in immune
      mediated, ischemic and degenerative diseases of the rat nervous system. In the
      acute phase of experimental autoimmune encephalomyelitis and neuritis VCAM-1 mRNA
      was expressed not only on the luminal surface of inflamed vessels but also in
      perivascular cells suggesting a functional role of VCAM-1 in both endothelial
      adhesion and local restimulation of autoantigen-specific T cells. Accordingly,
      perivascular T cell accumulation was most pronounced at sites of local VCAM-1
      mRNA expression. In addition, VCAM-1 mRNA was detected in the border zone around
      photochemically induced cerebral infarcts which is the predeliction site of T
      cell infiltration and expression of immune activation markers during the first
      week after ischemia. VCAM-1 mRNA was absent from the center of the infarcts as
      well as axotomized central and peripheral nerves undergoing Wallerian
      degeneration. These data indicate that VCAM-1-mediated adhesion processes are
      involved in immune-mediated and ischemic diseases of the nervous system but not
      in T cell-independent macrophage recruitment during Wallerian degeneration.

PMID- 8862138
TI  - Measurement of early events in signal transduction beyond receptors involving G
      proteins function in mononuclear leucocytes.
AB  - G protein function in human mononuclear leucocytes was measured through
      isoproterenol, carbamylcholine and dopamine-enhanced 3H-Gpp(NH)p binding.
      Dopamine and carbamylcholine exerted their effects through D5 and M2 receptors,
      respectively. ADP-ribosylation by bacterial toxins indicates that dopamine and
      isoproterenol affected Gs, while carbamylcholine affected Gi. Quantitative G
      proteins measures were conducted through immunoblot analyses with specific
      polyclonal antibodies against G alpha s, and G alpha i subunits. Simultaneous
      functional and quantitative measures of G proteins showed significant
      correlations between function and immunoreactivities. Agonist-enhanced guanine
      nucleotide exchange is thus suggested as a method for measurement of early events
      in signal transduction beyond receptors in leucocytes, which can potentially
      serve for detecting alterations in G proteins measures in human disease.

PMID- 8862139
TI  - Elevated serum levels of interleukin-12 in chronic progressive multiple
      sclerosis.
AB  - The serum levels of the heterodimeric cytokine IL-12 were measured by solid-phase
      ELISA in a group of healthy subjects, multiple sclerosis (MS) patients with
      secondary chronic progressive course of the disease and patients suffering from
      other neurological diseases (OND). Serum levels of IL-12 higher than 5 pg/ml
      (limit of sensitivity of the assay) were only found in 2/30 (6.7%) of the healthy
      subjects and none of the 8 subjects with OND. In contrast, IL-12 was found in the
      majority of CPMS patients' sera (10/15, 66.7%) with values ranging between 5.5
      and 18.6 pg/ml. These results are suggestive for an up-regulated production of IL
      12 in CPMS.

PMID- 8862140
TI  - Effects of pH on vascular tension: which are the important mechanisms?
AB  - The pH has marked effects on the blood flow in several vascular beds but the
      underlying mechanisms remain incompletely understood. It is still not agreed, for
      example, whether it is the fall in extracellular pH or intracellular pH that is
      responsible for changes in tone resulting from hypercapnic acidosis. The issue
      has been further complicated by the recent discovery that nitric oxide (NO) may
      also be involved in vasodilator responses to hypercapnia with the result that, in
      some laboratories, attention has been focused away from vascular smooth muscle.
      The recent availability of fluorescent dyes sensitive to pH has enabled some of
      the uncertainties in this field to be addressed. In light of these new
      observations, we have attempted to put older viewpoints in perspective. We
      conclude that, whilst a fall in smooth muscle intracellular pH is likely to be
      responsible for immediate responses to acidosis, the extracellular pH probably
      plays the predominant role in the steady state. The role of NO is best
      investigated in the cerebral circulation where it plays an important modulating
      role in the response to acidosis, and is probably of extravascular origin.

PMID- 8862141
TI  - Pulsatile and steady flow-induced calcium oscillations in single cultured
      endothelial cells.
AB  - The influence of flow-imposed shear stress on the intracellular calcium
      concentration ([Ca2+]i) of cultured endothelial cells (ECs) remains incompletely
      understood. In the present study, we measured [Ca2+]i in single bovine aortic
      ECs, using fluorescence ratiometric image analysis. The effects of several flow
      patterns were analysed: steady shear stress (5-70 dyn/cm2), 1-Hz pulsatile shear
      stress (nonreversing 40 +/- 20 dyn/cm2, reversing 20 +/- 40 dyn/cm2, or purely
      oscillatory 0 +/- 20 dyn/cm2), or changing shear stress levels. Under all flow
      conditions, single-cell analyses revealed flow-induced asynchronous [Ca2+]i
      oscillations, which occurred randomly over the monolayer and which were not seen
      in the average [Ca2+]i signal corresponding to the monolayer response. The number
      of single-cell [Ca2+]i oscillations and the corresponding oscillation frequency
      rose as the shear stress associated with the steady flow increased: 0.06 +/- 0.02
      min-1 at 5 dyn/cm2, 0.19 +/- 0.03 min-1 at 20 dyn/cm2, and 0.28 +/- 0.02 min-1 at
      70 dyn/cm2 (means +/- SD). Also, the number of oscillations was greater for any
      type of pulsatile flow (0.53 +/- 0.07 min-1 at 40 +/- 20 dyn/cm2, 0.54 +/- 0.08
      min-1 at 20 +/- 40 dyn/cm2, and 0.39 +/- 0.07 min-1 at 0 +/- 20 dyn/cm2), as
      compared to any level of steady flow. The most dramatic finding was that purely
      oscillatory flow induced numerous single-cell [Ca2+]i oscillations, yet the
      average [Ca2+]i response for the monolayer did not change. Furthermore, an EC
      monolayer switched from low to high (or from high to low) steady flow
      consistently showed an increase (or a decrease) in the number of single-cell
      [Ca2+]i oscillations. These experiments show that ECs respond to different flow
      conditions by varying single-cell [Ca2+]i oscillatory activity. This may have
      important implications in the endothelium-dependent control of vascular
      physiology, such as the release of vasoactive substances.

PMID- 8862142
TI  - Rapid effect of LPS-activated macrophages on the reactivity of the rat mesenteric
      artery.
AB  - This study was designed to evaluate the effects of lipopolysaccharide (LPS)
      activated macrophages in the perfused mesenteric circulation of the rat. The
      mesenteric network of anesthetized rats was perfused in situ under constant flow
      conditions and the diameter and pressure of the mesenteric artery were
      continuously recorded. For the first 30 min the mesenteric network was perfused
      with an RPMI solution (control condition); thereafter it was perfused for 60 min
      with the same solution containing either (1) LPS (1 microgram/ml), (2) elicited
      macrophages (10(6) cells/ml), (3) LPS-activated macrophages or (4) supernatants
      derived from LPS-activated macrophages (SPN). The changes in arterial diameter
      induced by topical application of phenylephrine (PE, 10 mumol/l) were measured
      under control conditions and then 30 and 60 min after the onset of perfusions.
      The intravascular pressure was similarly increased (51 +/- 6%, p < 0.001) by the
      perfusion of activated macrophages or elicited macrophages but was not affected
      by perfusion of LPS or SPN. Despite the same level of transmural mesenteric
      pressure in rats perfused with activated and elicited macrophages, the mesenteric
      diameter was significantly larger with activated than with elicited macrophages
      (p < 0.05). Under control conditions, PE induced a marked decrease in arterial
      diameter from 495 +/- 15 to 265 +/- 13 microns (p < 0.001). Perfusion of LPS,
      elicited macrophages or SPN did not modify the vascular reactivity to PE.
      Perfusion of activated macrophages reduced the PE-induced contraction by 77 +/-
      6% (p < 0.001). Perfusion of elicited macrophages with a nitric oxide (NO) donor
      (SIN-1, 10 mumol/l) reproduced the effect of LPS-activated macrophages while
      addition of an NO scavenger (oxyhemoglobin, 10 mumol/l) prevented the depression
      of the vascular reactivity to PE by activated macrophages. Finally, activated
      macrophages preincubated with an inhibitor of NO synthesis (NG-monomethyl-L
      arginine); L-NMMA), and then perfused in RPMI solution without L-NMMA had no
      effect on the PE reactivity of the mesenteric artery suggesting that NO released
      by activated macrophages directly and rapidly inhibited the contractility of the
      mesenteric artery. The results of this study demonstrate the opposing effects of
      macrophages in the mesenteric circulation to increase microvascular resistance by
      a rheological effect while decreasing the reactivity of the mesenteric artery as
      a result of NO released by macrophages.

PMID- 8862143
TI  - Electrotonic propagation of kinin-induced, endothelium-dependent
      hyperpolarizations in pig coronary smooth muscles.
AB  - The kinins, substance P and bradykinin, cause endothelium-dependent
      hyperpolarizations in smooth muscles of the pig coronary artery. We tested
      whether the propagation, in the media, of these hyperpolarizations is passive or
      whether the hyperpolarizations are regenerated in the smooth muscle cells. The
      space constants measured in response to the kinin endothelium-dependent
      stimulations were compared to those obtained by electrical field stimulation. The
      space constant is 2.6 +/- 0.2 mm (n = 13) measured for substance P and 2.2 +/-
      0.2 mm (n = 12) for bradykinin. The space constants established by electrical
      field stimulation-induced hyperpolarization are 3 +/- 0.2 mm (n = 7) for strips
      with intact endothelium and 2.7 +/- 0.3 mm (n = 7) for strips with removed
      endothelium. These results show that the space constants obtained for the kinin
      stimulations are not larger than those caused by electrical field stimulation.
      This suggests that the kinin-induced hyperpolarizations propagate, in the media,
      in a passive, electronic manner, therefore the hypothesis of regenerated kinin
      hyperpolarizations is unlikely.

PMID- 8862144
TI  - Role of endothelial nitric oxide in the response to angiotensin II of small
      mesenteric arteries of the rat.
AB  - The role of endothelium-derived nitric oxide (NO) in the vascular contractile
      response to angiotensin II (Ang II) has been investigated in isolated small
      mesenteric resistance arteries of the rat. Both contraction and intracellular
      Ca2+ ion concentration ([Ca2+]i) were monitored in vessels, with and without
      functional endothelium, which were exposed to physiological salt solution
      containing 25 mM KCl. Ang II induced concentration-dependent contractile
      responses and increases in [Ca2+]i which, at the concentration giving the maximal
      response (10 nM), were not sustained in arteries with functional endothelium;
      however, the presence of a functional endothelium did not modify the peak
      responses. Ang II did not increase the cyclic guanosine 3',5'-monophosphate
      content of the tissue nor did it induce relaxation in arteries precontracted with
      3 microM noradrenaline. The decline of the Ang II responses was suppressed by
      removal of the endothelium or by exposure of arteries with endothelium to either
      the NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (300 microM),
      or the cyclic GMP-dependent protein kinase inhibitor, Rp-8-bromoguanosine 3',5'
      cyclic monophosphorothioate (30 microM). On the other hand, the NO donor SIN-1 (3
      morpholino-sydnonimine, 10 microM) accelerated the decline in [Ca2+]i and
      contraction. These results show that endothelium-derived NO does not affect the
      magnitude of the phasic element of the response to Ang II, but is involved in the
      rapid attenuation of the tonic component. Activation of cyclic GMP-dependent
      protein kinase accounts for this effect of endothelium-derived NO.

PMID- 8862146
TI  - Comparison of the effects of mechanical stimulation on venous and arterial smooth
      muscle cells in vitro.
AB  - The proliferation of intimal smooth muscle cells (SMCs) in large muscular
      arteries and veins often occurs after surgical interventions such as angioplasty
      and bypass grafting, and may lead to restenosis and graft failure. Clinical
      observations suggest that increased pulsatile deformation of veins grated into an
      arterial position may play a role in intimal hyperplasia. Since intimal
      hyperplasia occurs at the vein/arterial interface of the graft, SMC hyperplasia
      could be due to the proliferation of either aortic or venous SMCs. Therefore, we
      compared the effects of in vitro mechanical deformation on the proliferation of
      aortic SMCs with venous SMCs. Using the Flexercell apparatus (Flexercell Corp.,
      McKeesport, Pa., USA), aortic SMCs, stretched at 3 and 60 cpm did not lead to a
      significant increase in growth as compared to the nonstretched controls. In
      contrast, stretch of venous SMCs at 3 and 60 cpm led to a significant increase in
      growth as compared to the nonstretched controls. These results suggest that the
      SMC proliferation, as occurs in vein interposition grafts in vivo, may be
      partially due to a stimulatory response by venous SMCs to increased mechanical
      stimulation.

PMID- 8862145
TI  - Inhibition of nitric oxide-induced vasodilation by gap junction inhibitors: a
      potential role for a cGMP-independent nitric oxide pathway.
AB  - Studies have provided evidence for the role of gap junctional intercellular
      communication in syncytial tissue function. This study tested the hypothesis that
      the vasodilating effects of nitric oxide (NO) rely on gap junctions. The effects
      of the gap junction inhibitors octanol (10(-4) mol/l) and heptanol (10(-3) mol/l)
      were examined on acetylcholine-, the NO-donor S-nitroso-N-acetyl-penicillamine
      (SNAP)-, and guanosine-3',5'-cyclic monophosphate (cGMP)-induced relaxation. In
      addition, we tested varying concentrations of the gap junction inhibitor sucrose
      on SNAP-induced relaxation in the presence and absence of methylene blue, an
      inhibitor of guanylate cyclase. Helical strips of rat thoracic aorta were placed
      in muscle baths for isometric force measurements. Tissues treated with SNAP and
      cGMP were denuded of endothelium. Tissues incubated in octanol and heptanol
      exhibited 4- to 7-fold rightward shifts in acetylcholine-induced and 6- to 15
      fold rightward shifts in SNAP-induced relaxation. Both octanol and heptanol
      produced 2-fold rightward shifts in cGMP-induced relaxation, comparably less in
      magnitude than shifts produced in acetylcholine- and SNAP-induced relaxation.
      Sucrose (10(-2) to 10(-1) mol/l) produced a concentration-dependent rightward
      shift of up to 30-fold in relaxation to SNAP. Incubation with methylene blue (10(
      6) mol/l) altered this rightward shift only slightly, indicating a possible cGMP
      independent mechanism for NO. These findings support the hypothesis that NO
      induced vasodilation, through both cGMP-dependent and -independent pathways,
      relies on gap junctional communication.

PMID- 8862147
TI  - Potentiation of acetylcholine-induced responses in freshly isolated rabbit aortic
      endothelial cells.
AB  - Acetylcholine (ACh)-induced membrane hyperpolarization was studied in freshly
      isolated endothelial cells from rabbit aorta. Ten microM ACh induced transient
      hyperpolarization due to the opening of Ca(2+)-sensitive K+ channels, sensitive
      to TEA and charybdotoxin (CTX). The membrane potential response was accompanied
      by an increase in intracellular Ca2+ [Ca2+]i. Pretreatment of endothelial cells
      with 20 microM ATP, 0.2 microM bradykinin or 0.1 microM platelet-aggregating
      factor, which induced either a transient hyperpolarization or no response,
      changed the subsequent ACh-induced response to a large maintained
      hyperpolarization. This sustained membrane hyperpolarization was also due to the
      opening of Ca(2+)-activated K+ channels as confirmed by CTX and TEA blockade, and
      was related to elevated [Ca2+]i measured by fura-2 fluorescence. Pertussis toxin
      blocked potentiation, indicating involvement of a G protein. The linkage to
      receptor-operated Ca2+ (ROC)-entry was suggested by observations that the
      maintained hyperpolarization during potentiation was dependent on extracellular
      Ca2+ and was abolished by the ROC blockers SKF-96365 and Ni2+. Inhibition of the
      Ca2+ pump of the endoplasmic reticulum mimicked the potentiating effect of the
      agonists. The results suggest that crosstalk between the agonists in endothelial
      cells involves Ca2+ movements and that this crosstalk is important for the
      generation of endothelial secretions.

PMID- 8862148
TI  - Localisation of endothelin-1 in rat aortae, the relationship to flow and elastic
      tissue tears.
AB  - The aortic expression of endothelin-1 (ET-1) was examined in three species of rat
      using a novel en face immunohistochemical technique. A genetically hypertensive
      strain was compared to two normotensive strains, one of which is known to develop
      spontaneous lesions within the abdominal aorta. ET-1-positive staining was
      increased about the major aortic branch ostia and over the dorsal abdominal
      aortic wall in all three species indicating a flow-related expression pattern.
      Mitotic and hyperchromatic endothelial cells stained strongly for ET-1 as did
      occasional multi-nucleated endothelial cells. The aortic-lesion-prone
      normotensive strain developed transverse tears of the internal elastic lamina
      with a corresponding endothelial cell response. Endothelium at the edge of these
      lesions was strongly stained for ET-1 and appeared to be associated with
      increased leucocyte adhesion as did other strongly ET-1-stained areas in all
      three species. This study indicates that increased ET-1 expression is
      anatomically localised within the rat aorta, possibly by haemodynamic stress.
      This may have implications for maintaining endothelial cell confluence, aortic
      smooth muscle cell reparative processes and possibly eventual pathophysiological
      conditions such as atherosclerosis.

PMID- 8862149
TI  - The importance of behavioral science in HIV prevention.

PMID- 8862150
TI  - Bridging the gap between behavioral science and public health practice in HIV
      prevention.

PMID- 8862151
TI  - Behavioral science and public health: a necessary partnership for HIV prevention.

PMID- 8862152
TI  - Adaptation of behavioral theory to CDC's HIV prevention research: experience at
      the Centers for Disease Control and Prevention.

PMID- 8862153
TI  - The use of theory based semistructured elicitation questionnaires: formative
      research for CDC's Prevention Marketing Initiative.
AB  - Through one of its many HIV prevention programs, the Prevention Marketing
      Initiative, the Centers for Disease Control and Prevention promotes a
      multifaceted strategy for preventing the sexual transmission of HIV/AIDS among
      people less than 25 years of age. The Prevention Marketing Initiative is an
      application of marketing and consumer-oriented technologies that rely heavily on
      behavioral research and behavior change theories to bring the behavioral and
      social sciences to bear on practical program planning decisions. One objective of
      the Prevention Marketing Initiative is to encourage consistent and correct condom
      use among sexually active young adults. Qualitative formative research is being
      conducted in several segments of the population of heterosexually active,
      unmarried young adults between 18 and 25 using a semistructured elicitation
      procedure to identify and understand underlying behavioral determinants of
      consistent condom use. The purpose of this paper is to illustrate the use of this
      type of qualitative research methodology in designing effective theory-based
      behavior change interventions. Issues of research design and data collection and
      analysis are discussed. To illustrate the methodology, results of content
      analyses of selected responses to open-ended questions on consistent condom use
      are presented by gender (male, female), ethnic group (white, African American),
      and consistency of condom use (always, sometimes). This type of formative
      research can be applied immediately to designing programs and is invaluable for
      valid and relevant larger-scale quantitative research.

PMID- 8862154
TI  - Using formative research to lay the foundation for community level HIV prevention
      efforts: an example from the AIDS Community Demonstration Projects.
AB  - The AIDS Community Demonstration Projects provided community-level HIV prevention
      interventions to historically hard-to-reach groups at high risk for HIV
      infection. The projects operated under a common research protocol which
      encompassed formative research, intervention delivery, process evaluation, and
      outcome evaluation. A formative research process specifically focusing on
      intervention development was devised to assist project staff in identifying,
      prioritizing, accessing, and understanding the intervention target groups. This
      process was central to the creation of interventions that were acceptable and
      unique to the target populations. Intended to be rapid, the process took 6 months
      to complete. Drawn from the disciplines of anthropology, community psychology,
      sociology, and public health, the formative research process followed distinct
      steps which included (a) defining the populations at high-risk for HIV; (b)
      gathering information about these populations through interviews with persons who
      were outside of, but who had contact with, the target groups (such as staff from
      the health department and alcohol and drug treatment facilities, as well as
      persons who interacted in an informal manner with the target groups, such as
      clerks in neighborhood grocery stores and bartenders); (c) interviewing people
      with access to the target populations (gatekeepers), and conducting observations
      in areas where these high-risk groups were reported to gather (from previous
      interviews); (d) interviewing members of these groups at high risk for HIV
      infection or transmission; and (e) systematically integrating information
      throughout the process. Semistructured interview schedules were used for all data
      collection in this process. This standardized systematic method yielded valuable
      information about the focal groups in each demonstration project site. The
      method, if adopted by others, would assist community intervention specialists in
      developing interventions that are culturally appropriate and meaningful to their
      respective target populations.

PMID- 8862155
TI  - Non-gay-identifying men who have sex with men: formative research results from
      Seattle, Washington.
AB  - Non-gay-identifying men who have sex with men are at risk for human
      immunodeficiency virus (HIV) infection. To understand these men and to develop
      interventions to reduce their HIV risks, the authors interviewed staff at
      agencies that serve non-gay-identifying men who have sex with men, business
      people who interact with them, and the men themselves. Interviews were augmented
      with focus groups of non-gay-identifying men who have sex with men and field
      observations at sites identified as places where they meet to negotiate or have
      sex. These qualitative data suggested 73 possible groups, which were consolidated
      into 16 broader "sectors," and then formally ranked by level of HIV risk, ease of
      access to the sector, psychosocial risks, and influence of other local
      interventions or research activities. The authors identified six priority groups
      of non-gay-identifying men who have sex with men (and sites where members of
      these groups could be approached): hustlers, closeted men, experimenters,
      incarcerated or formerly incarcerated men, men of color, and heterosexually
      identified bisexuals. Masturbation and oral sex were reportedly common, but anal
      and vaginal sex were also noted; condom use was rarely reported. Risk behaviors
      among non-gay-identifying men who have sex with men persist for a variety of
      reasons and may require a variety of intervention approaches.

PMID- 8862156
TI  - Developing community networks to deliver HIV prevention interventions.
AB  - Outreach has a long history in health and social service programs as an important
      method for reaching at-risk persons within their communities. One method of
      "outreach" is based on the recruitment of networks of community members (or
      "networkers") to deliver HIV prevention messages and materials in the context of
      their social networks and everyday lives. This paper documents the experiences of
      the AIDS Community Demonstration Projects in recruiting networkers to deliver HIV
      prevention interventions to high-risk populations, including injecting drug users
      not in treatment; female sex partners of injecting drug users; female sex
      traders; men who have sex with men but do not self-identify as gay; and youth in
      high-risk situations. The authors interviewed project staff and reviewed project
      records of the implementation of community networks in five cities. Across
      cities, the projects successfully recruited persons into one or more community
      networks to distribute small media materials, condoms, and bleach kits, and
      encourage risk-reduction behaviors among community members. Networkers'
      continuing participation was enlisted through a variety of monetary and
      nonmonetary incentives. While continuous recruitment of networkers was necessary
      due to attrition, most interventions reported maintaining a core group of
      networkers. In addition, the projects appeared to serve as a starting point for
      some networkers to become more active in other community events and issues.

PMID- 8862157
TI  - Building a peer network for a community level HIV prevention program among
      injecting drug users in Denver.
AB  - As part of a multi-site Centers for Disease Control and Prevention-funded
      initiative, a community-level HIV prevention project targeting injection drug
      users was implemented in the FivePoints community in Denver, Colorado. The
      protocol for the initiative included the use of peer networks to conduct outreach
      and disseminate intervention materials to injecting drug users. Since April 1993,
      project staff established a peer network of 119 participants who distribute
      approximately 3,000 materials per month.

PMID- 8862158
TI  - Development and use of role model stories in a community level HIV risk reduction
      intervention.
AB  - A theory-based HIV prevention intervention was implemented as part of a five-city
      AIDS Community Demonstration Project for the development and testing of a
      community-level intervention to reduce AIDS risk among historically underserved
      groups. This intervention employed written material containing stories of risk
      reducing experiences of members of the priority populations, in this case,
      injecting drug users, their female sex partners, and female sex workers. These
      materials were distributed to members of these populations by their peers,
      volunteers from the population who were trained to deliver social reinforcement
      for interest in personal risk reduction and the materials. The participation of
      the priority populations in the development and implementation of the
      intervention was designed to increase the credibility of the intervention and the
      acceptance of the message. The techniques involved in developing role-model
      stories are described in this paper.

PMID- 8862159
TI  - Measuring the adoption of consistent use of condoms using the stages of change
      model. AIDS Community Demonstration Projects.
AB  - The stages of behavior change model has been used to understand a variety of
      health behaviors. Since consistent condom use has been promoted as a risk
      reduction behavior for prevention of human immunodeficiency virus (HIV)
      infection, an algorithm for staging the adoption of consistent condom use during
      vaginal sex was empirically developed using three considerations: HIV prevention
      efficacy, analogy with work on staging other health-related behaviors, and condom
      use data from groups at high risk for HIV infection. This algorithm suggests that
      the adoption of consistent condom use among persons at high risk can be
      meaningfully measured with the model. However, variations in the algorithm
      details affect both the interpretation of stages and apportionment of persons
      across stages.

PMID- 8862160
TI  - Defining the components of street outreach for HIV prevention: the contact and
      the encounter.
AB  - Health departments and community-based organizations across the United States are
      funded by the Centers for Disease Control and Prevention to conduct street
      outreach to facilitate risk reduction among a variety of hard-to-reach
      populations who are at risk for human immunodeficiency virus infection and other
      sexually transmitted diseases. The interaction between the client and outreach
      worker is the fundamental element of any street outreach activity. However,
      little has been written about the relationships that develop on the street
      between workers and clients to promote, support, and sustain behavior change.
      This paper describes two types of interactions that occur in street outreach
      intervention activities: the contact and the encounter. As part of a
      comprehensive evaluation of street outreach, interactions between workers and
      clients were described and analyzed during the formative phase of the AIDS
      Evaluation of Street Outreach Projects. For purposes of the evaluation, a contact
      was defined as a face-to-face interaction during which materials and/or
      information are exchanged between an outreach worker and a client (or small group
      of clients). An encounter was defined as a face-to-face interaction between a
      worker and client going beyond the contact to include individual assessment,
      specific service delivery in response to the client's identified need(s), and a
      planned follow-up. The contact provides a means to initiate interaction with
      potential clients in the community. It is the encounter that provides more
      significant opportunity for helping the client initiate and sustain behavior
      change. The discussion suggests techniques for enhancing the encounter between
      outreach workers and clients using the conceptual framework of the social work
      helping relationship. Five elements of the encounter are defined and developed:
      screening, engagement, assessment, service delivery, and follow-up. The encounter
      represents an enhancement of the traditional street outreach interaction and a
      more systematic approach to promoting the behavioral change goals of the AIDS
      Evaluation of Street Outreach Projects. Recommendations are suggested for
      implementing the encounter in street outreach programs serving hard-to-reach
      populations.

PMID- 8862161
TI  - Paraprofessional delivery of a theory based HIV prevention counseling
      intervention for women.
AB  - This report describes a mid-course process evaluation of an HIV risk-reduction
      counseling intervention delivered by specially trained peer paraprofessionals.
      One of the key questions addressed is whether paraprofessionals can successfully
      implement a theory-based counseling intervention. The project, known as Project
      CARES, is a 5-year demonstration research project to prevent HIV infection and
      unplanned pregnancies in women at risk for HIV infection and transmission who
      were recruited from homeless shelters, drug treatment facilities, and hospital
      based service settings for HIV-infected women. Project CARES uses an enhanced
      counseling intervention based on the Transtheoretical Model, also known as the
      Stages of Change model, to promote condom and other contraceptive use for women
      who wish to avoid pregnancy, condom use for disease prevention, and reproductive
      health service use. Peer paraprofessionals, called advocates, provide stage
      tailored counseling using a structured manual which guides them in the selection
      of specific counseling activities appropriate to a woman's level of readiness to
      change her behavior. Data from process evaluation forms completed by advocates in
      Philadelphia and Baltimore document that the delivery of the intervention is
      consistent with the theoretical model upon which it was based. Paraprofessionals
      can become skilled in the delivery of a stage-based counseling intervention in
      health and social service settings. The use of paraprofessionals in HIV
      prevention service delivery may be a cost-effective way to enhance and extend
      services for women.

PMID- 8862162
TI  - Integrating a theoretical framework with street outreach services: issues for
      successful training.
AB  - HIV/AIDS prevention projects utilizing indigenous outreach workers often rely on
      the life experiences and skills of the staff to structure the intervention,
      without grounding in theory. However, to be most effective, community outreach
      projects which target harder-to-reach high-risk populations should both utilize
      and enhance the natural strengths of indigenous field workers' experience and
      style of interaction, while guiding intervention content with theoretical rigor.
      In this paper we demonstrate that the challenge of successfully integrating a
      theoretically guided program design with field staff's credibility with, and
      sensitivity toward, drug-using clients can be practically and satisfactorily met
      through appropriate training. This training is an important investment for better
      utilizing valued and scarce prevention resources. The Philadelphia site of the
      AIDS Evaluation of Street Outreach Project (AESOP), a cooperative agreement of
      the Centers for Disease Control and Prevention, designed and implemented staff
      trainings to reflect the enhancement of the outreach program by the Stages of
      Change model. Through these trainings, the outreach workers have learned to
      integrate their natural street and intervention skills into the structure of a
      theoretical framework. This paper presents specific training components, relevant
      issues within these components, and areas for evaluation and feedback.

PMID- 8862163
TI  - A model of community mobilization for the prevention of HIV in women and infants.
      Prevention of HIV in Women and Infants Demonstration Projects.
AB  - The prevention of HIV in Women and Infants Demonstration Projects use a
      conceptual model for maximizing broad community participation for HIV prevention
      called the Community Mobilization Framework. The projects' comprehensive approach
      attempts to bring about changes on a community level using a model which
      encourages community-wide participation of persons with various roles and
      relationships in the community. The Community Mobilization Framework is one way
      to systematically conceptualize the organization of the community for the purpose
      of mobilizing the maximum number of community members around a common health
      initiative. A community becomes mobilized around an issue by endorsing health
      enhancing attitudes, behaviors, and projects supporting positive health outcomes.
      This mobilization is expressed through the promotion, support, and delivery of
      motivational and informational health messages which convey consistent ideas,
      themes, and images. There are two fundamental bases of the Community Mobilization
      Framework. The first is its characterization of the variety of individual,
      social, and organizational roles and relationships in the community that might be
      used in a concerted campaign for HIV prevention for women. The second basis of
      the model is the description of the nature and extent of the involvement, which
      includes a continuum of involvement, ranging from simple endorsement to building
      active coalitions around a health initiative. The paper discusses practical
      methods of applying these principles, with the Women and Infants Demonstration
      Projects providing concrete examples.

PMID- 8862164
TI  - Quality assurance of HIV prevention counseling in a multi-center randomized
      controlled trial. Project RESPECT Study Group.
AB  - Current HIV prevention counseling strategies rely largely on interventions aimed
      at changing behaviors. Among these is HIV prevention counseling and testing,
      which has been a prominent component in the federally supported strategies for
      HIV/AIDS prevention in the United States. To assess the efficacy of HIV
      counseling in reducing risk behaviors and preventing HIV infection and other
      sexually transmitted diseases, a multicenter, randomized controlled trial is
      being conducted among sexually transmitted disease clinic patients (Project
      RESPECT). The trial compares three separate HIV prevention strategies on
      increasing condom use and decreasing new cases of sexually transmitted diseases.
      The strategies are (a) Enhanced HIV Prevention Counseling, a 4-session individual
      counseling intervention based on behavioral and social science theory; (b) HIV
      Prevention Counseling, a 2-session individual pre- and post test counseling
      strategy that attempts to increase perception of risk and reduce risk behaviors
      using small, achievable steps; and (c) HIV Education, a brief 2-session pre- and
      post-test strategy that is purely informational. One difficulty in conducting
      randomized trials of behavioral interventions is assuring that the interventions
      are being conducted both as conceptualized and in a consistent manner by
      different counselors and, for multicenter studies, at different study sites. This
      article describes the quality assurance measures that have been used for Project
      RESPECT. These have included development of standard tools, standard training,
      frequent observation and feedback to study personnel, and process evaluation.

PMID- 8862165
TI  - Methodological issues in evaluating HIV prevention community planning.
AB  - To be effective, HIV prevention programs should be planned in partnership with
      affected communities and should be built on a solid scientific foundation. In
      1994, the Centers for Disease Control and Prevention (CDC) and its prevention
      partners implemented HIV prevention community planning to achieve primarily these
      two objectives. In order to manage the community planning process effectively,
      extensive evaluation activities were employed at both the grantee and national
      level. This paper describes the first year evaluation goals and methods in
      detail. Throughout, reasons for collecting specific types of information and for
      using particular methodologies are highlighted.

PMID- 8862166
TI  - A method to measure the costs of counseling for HIV prevention.
AB  - This paper describes a method for estimating the true resource costs of
      counseling for HIV prevention. The method includes identifying the resources used
      in counseling, determining the true unit costs of the resources used, and
      calculating the total costs of counseling. Cost equations and sample calculations
      of total and expected costs per client in a specified time period are provided.
      This method of estimating costs provides a systematic application of a standard
      set of procedures, including sample tables and calculations. It uses the societal
      perspective on resource cost to determine true resource costs. This method can be
      used for resource allocation decisions among programs and as inputs for cost
      effectiveness and cost-benefit analyses. Since the method minimizes the burden of
      data collection and calculations, it is useful for the nonspecialist in cost
      analysis. The method provides a rational approach for realistic decision making
      and planning in public health.

PMID- 8862167
TI  - Surveillance of HIV knowledge, attitudes, beliefs, and behaviors in the general
      population.
AB  - This article discusses methods and elements of three major national health survey
      systems, particularly as they relate to HIV infection and AIDS. The National
      Health Interview Survey and the Behavioral Risk Factor Surveillance System
      provide information about health-related knowledge, attitudes, beliefs, and
      behaviors of adults in the United States. The Youth Risk Behavior Surveillance
      System measure health-related behaviors of American youth. Questions and survey
      designs differ among the three surveys, but all three surveys utilize probability
      sampling. The National Health Interview Survey's AIDS Knowledge and Attitudes
      Supplement is administered to a subsample of approximately 20,000 people
      annually. The Behavioral Risk Factor Surveillance System consists of telephone
      surveys providing data for all 50 states and the District of Columbia, with an
      average annual sample size of approximately 2,000 per state. The Youth Risk
      Behavior Surveillance System samples approximately 12,000 youth for its national
      school-based survey, 2,000 (average) for each of its state and local school-based
      surveys, 10,000 for its national household-based survey, and 6,000 (projected)
      for its national college-based survey. This article is meant to assist
      researchers, students, health educators, public health officials and others in
      utilizing survey data bases to address policy, program, research, and evaluation
      needs. All three surveys can help guide prevention efforts by providing
      information about the general population and by identifying national, local, or
      state-wide trends. More detailed studies and targeted studies of specific high
      risk populations are also needed in light of the complexity of the determinants
      of HIV risk behavior.

PMID- 8862168
TI  - CDC data systems collecting behavioral data on HIV counseling and testing.
AB  - This paper describes two systems, the HIV Counseling and Testing Data System and
      the National Health Interview Survey, AIDS Knowledge and Attitudes Supplement,
      that collect behavioral information on HIV counseling and testing in the United
      States. Together these data sources provide valuable information for planning and
      evaluating counseling and testing programs. While these two systems are not
      designed primarily for behavioral research, they both collect behavioral data,
      including the behavioral risk category of persons being tested.

PMID- 8862169
TI  - The supplement to HIV-AIDS Surveillance project: an approach for monitoring HIV
      risk behaviors.
AB  - A variety of surveillance methods are used to characterize the epidemic of HIV
      infection and AIDS. Such surveillance includes AIDS case reporting, reporting of
      diagnosed HIV infections, and HIV seroprevalence surveys among targeted sentinel
      populations. The need for additional surveillance systems to monitor HIV-related
      risk behaviors has been increasingly evident. One approach to behavioral
      surveillance, the CDC's Supplement to HIV-AIDS Surveillance project, uses the
      infrastructure of HIV infection and AIDS case reporting to collect additional
      information on risk behaviors among HIV-infected persons, who by definition
      represent those at highest risk.

PMID- 8862170
TI  - The Young Men's Survey: methods for estimating HIV seroprevalence and risk
      factors among young men who have sex with men.
AB  - Traditional sampling methods are unsuitable for determining the levels of human
      immunodeficiency virus type I infection and related behavioral risk factors among
      young men who have sex with men. Most surveys of this hard-to-reach population
      have used nonprobability samples of young men in clinical or public settings.
      While these studies have revealed high rates of HIV infection and risk behaviors,
      their findings are not generalizable to broader populations of young men who have
      sex with men. To better understand the epidemiology of HIV within this
      population, the Centers for Disease Control and Prevention, in collaboration with
      state and local health departments, has developed a venue-based probability
      survey of young men who have sex with men. Conducted in seven metropolitan areas
      in the United States, the Young Men's Survey combines outreach techniques with
      standard methods of sample surveys to enumerate, sample, and estimate prevalence
      outcomes of a population of young men who frequent public venues and who have sex
      with other men. Venues where young men who have sex with men are sampled include
      dance clubs, bars, and street locations. At sampled venues, young men are
      enumerated, consecutively approached, and offered enrollment if they are
      determined eligible. Young men who agree to participate in the Young Men's Survey
      are interviewed, counseled, and tested for human immunodeficiency virus,
      hepatitis B, and syphilis in vans parked near sampled venues. The Young Men's
      Survey provides data on the locations and times at which demographic and
      behavioral subgroups of young men who have sex with men may be targeted for
      prevention activities. Behaviors and psychosocial factors associated with human
      immunodeficiency virus infection can be used to design culturally relevant and
      age-specific prevention activities for young men who have sex with men.

PMID- 8862171
TI  - Theatrum vacunae.

PMID- 8862172
TI  - New approaches to the mapping of chromosomal domains.
AB  - Although it is generally accepted that the chromosome is divided into elementary
      subunits, the structural and functional domains, the organisation of these
      structures at the molecular level is not well understood. In particular, the
      domain boundaries are not easily identifiable. Several possible candidates such
      as MARs/SARs, insulators, LCRs, palindromic sequences, or easily melting
      sequences have been found in the regions having properties one would except for
      boundaries. None of these elements, however, has been found in all of the
      constructs functioning as boundaries in tests in vivo. Recent work suggests that
      the common denominator might be the presence og GC-rich oligonucleotide stretches
      and the formation of the chromatin hypersensitive sites. A model is discussed in
      which "unusual" structures, in particular the four-stranded DNA sequence elements
      containing unpaired bases, play the role of domain boundaries.

PMID- 8862173
TI  - On the strategy of using nonviral carriers in cancer gene therapy.
AB  - Effectiveness and mode of therapeutic gene delivery in vivo as well as biological
      safety of such transfer must be improved before widespread application of gene
      therapy in the clinic becomes possible. Most research has so far focused on
      recombinant viral delivery systems. Clinical future seems to belong, however, to
      nonviral delivery systems. Such systems feature DNA complexed to lipid, protein,
      peptide or polymeric carriers with ligands allowing in vivo tissue targeting by
      the complex and nuclear translocation of the exogene. Nonviral gene carrier
      systems are discussed together with strategies of destroying cancer cells.

PMID- 8862174
TI  - Recent avenues of chemotherapeutic research.

PMID- 8862175
TI  - DNA adducts in environmental, occupational and life-style studies in human
      biomonitoring.
AB  - The importance of DNA adducts in carcinogenesis had been discussed. The 32P
      postlabelling method was developed as a quantitative technique to measure the
      level of different DNA adducts including adducts in human DNA. The elevated level
      of DNA adducts was found in white blood cells in persons exposed environmentally
      and occupationally to high concentrations of PAHs (polycyclic aromatic
      hydrocarbons) in the ambient air. Tobacco also generated higher level of DNA
      adducts both in lymphocytes and laryngeal tissues of smokers. Exposure to styrene
      has been of interest world-wide because of the very high exposure and persistence
      of adducts in DNA of lamination workers.

PMID- 8862176
TI  - Construction of cDNA library from liver RNA of heat shocked rats and DNA sequence
      analysis of the clone containing the 3'-end untranslated region (3'UTR) of the
      heat inducible gene hsp70.2.
AB  - cDNA library constructed from liver RNA of rats subjected to hyperthermia was
      used to isolate divergent 3' end untranslated regions (3'UTR) of heat inducible
      hsp70.1 and hsp70.2 genes. As a result of a double selection procedure with the
      use of DNA-DNA hybridization and PCR analysis 9 clones containing cDNA sequences
      derived from the 3'UTR of the hsp70.2 gene were selected. Nucleotide sequence of
      the cloned inserts was established and the Northern blot analysis was performed
      to identify the heat inducible transcript encoded by the hsp70.2 gene.

PMID- 8862177
TI  - Interactions of rat repetitive sequence MspI8 with nuclear matrix proteins during
      spermatogenesis.
AB  - Using the Southwestern blot analysis we have studied the interactions between rat
      repetitive sequence MspI8 and the nuclear matrix proteins of rat testis cells.
      Starting from 2 weeks the young to adult animals showed differences in type of
      testis nuclear matrix proteins recognizing the MspI8 sequence. The same sets of
      nuclear matrix proteins were detected in some fractions enriched in spermatocytes
      and spermatides and obtained after fractionation of testis cells of adult animals
      by the velocity sedimentation technique.

PMID- 8862178
TI  - Presynaptic phosphoprotein B-50/GAP-43 in neuronal and synaptic plasticity.
AB  - B-50/GAP-43 is a growth-associated phosphoprotein enriched in growth cones and in
      the presynaptic terminal. The expression of the protein is restricted to the
      nervous system and is highest in the first week after birth. In adult brain, B-50
      is enriched in areas with high plasticity. The regulation of expression of the B
      50 gene occurs both at the transcriptional and post-transcriptional level by
      unknown mechanisms. The gene contains 2 regions displaying promoter activity, the
      most 3' of which (P2) is the active on in vivo. Expression of B-50 in non
      neuronal cells results in filopodial extensions whereas antibodies or antisense
      oligo's to B-50 prevent neurite outgrowth. The protein is important for neuronal
      pathfinding. Several post-translational modifications have been described, ADP
      ribosylation and palmitoylation in the membrane binding domain, phosphorylation
      by PKC, casein kinase II and phosphorylase kinase, and dephosphorylation by
      several phosphatases, among which is calcineurin. Interactions of B-50 have been
      described with calmodulin, PIP kinase, F-actin, and phospholipids. Recent studies
      indicate that the phosphorylation state and amount of calmodulin bound to B-50
      regulate the rate of transmitter release. Induction of long-term potentiation by
      high frequency stimulation of hippocampal slices results in an increased state of
      B-50 phosphorylation. This will increase the amount of free calmodulin in the
      presynaptic terminal and increase the amount of transmitter released. Although B
      50 is involved in seemingly unrelated forms of neuronal plasticity, neurite
      outgrowth and transmitter release, our unifying hypothesis is that the protein
      plays an (unknown) essential, modulatory role in membrane expansion.

PMID- 8862179
TI  - Applications of impedance spectroscopy in biochemistry and biophysics.
AB  - The present study is intended to demonstrate the application of impedance
      spectroscopy to two very different fields of biophysical research. The core
      component of our measuring setup is a self-constructed continuous wave impedance
      spectrometer together with special measuring chambers which are individually
      designed for the systems under investigation. We directed our attention towards:
      i) the investigation of solid supported lipid bilayers in general, especially
      systems which are suitable for protein reconstitution such as
      dimethyldioctadecylammonium bromide (DODAB) immobilized onto a gold electrode,
      precovered with a negatively charged monolayer of 3-mercaptopropionic acid.
      Impedance spectroscopy allows to study the stability, the thickness and the
      electrode coverage of those artificial membranes as well as the observation of
      ion transport mediated by ionophores like gramicidin D incorporated into a DODAB
      bilayer. ii) The characterization of the passive electrical properties of
      epithelial and endothelial cell monolayers in general and especially the
      determination of their transepithelial (transendothelial) electrical resistances
      as a measure for epithelial barrier function. From impedance spectra, as reported
      here, we are able to follow the formation and modulation of cell layer
      permeability to small ions.

PMID- 8862180
TI  - Mitochondrial metabolite carrier family, topology, structure and functional
      properties: an overview.
AB  - A set of metabolite carriers operates the traffic of numerous molecules consumed
      or produced in mitochondrial matrix and/or cytosolic compartments. As their
      existence has been predicted by the chemiosmotic theory, the first challenge, in
      the late sixties, was to prove their presence in the inner mitochondrial membrane
      and to describe the various transports carried out. The second challenge was to
      understand their mechanisms by the kinetic approach in intact mitochondria
      (seventies). The third challenge (late seventies-eighties) was to isolate and to
      reconstitute the carriers in liposomes in order to characterize the proteins and
      to establish the concept of a structural and a functional family as well as some
      structure-function relationship with the help of primary sequences. Genetics,
      molecular biology and genomic sequencing bring the fourth challenge (nineties): a
      raising number of putative carriers becomes known only by their primary sequences
      but their functions have to be discovered. The actual challenge of the future is
      the elucidation of the ternary structure of carrier proteins that together with
      site-directed mutagenesis and kinetic mechanism will permit to advance in the
      understanding of molecular mechanisms of transport processes.

PMID- 8862181
TI  - The Crabtree effect: a new look at the old problem.
AB  - Inhibition of respiration by glucose, known as the Crabtree effect, has been
      observed in several tumours and some other highly glycolytic cells and tissues.
      Among mechanisms proposed to explain this effect were: competition between
      glycolysis and respiration for ADP or for inorganic phosphate, change of
      intracellular pH, change in the permeability of mitochondrial membranes, specific
      regulatory behavior of glycolytic enzymes, and specific enzyme topography within
      the cell. None of these proposals alone seems satisfactory. The present article
      describes the research carried out in the author's laboratory, pointing to the
      role of Ca2+ in the mechanism of the Crabtree effect. This supposition is based
      on the following observations: (1) in Ehrlich ascites tumour cells glucose
      elicits a steady increase of the cytoplasmic concentration of free Ca2+; (2)
      isolated Ehrlich ascites mitochondria and mitochondria within digitonin
      permeabilised cells, preloaded with Ca2+, exhibit a depression of State 3
      respiration and lowering of the rate of ATP synthesis; (3) ATPase activity of
      toluene-permeabilised Ehrlich ascites mitochondria becomes substantially
      inhibited at micromolar concentrations of Ca2+; (4) Ca2+ potentiates the effect
      of the inhibitory subunit of F1F0-ATPase. These results allow to hypothesize on
      the following sequence of events: (1) glucose elevates the cytoplasmic
      concentration of Ca2+; (2) this elicits an increased accumulation of Ca2+ in
      mitochondria; (3) loading of mitochondria with Ca2+ leads to an increased
      association of the inhibitory subunit with F1F0 which results in (4) the
      inhibition of coupled respiration. The importance of these mechanisms for
      glycolytic and rapidly proliferating cells is discussed.

PMID- 8862182
TI  - Regulation of protamine gene expression in an in vitro homologous system.
AB  - An in vitro transcription system from the trout testis nuclei was developed to
      study trout protamine gene expression. The protamine promoter contains, among
      others, two regulatory elements: 1) a cAMP-responsive element or CRE element
      (TGACGTCA) which is present in position 5' to TATA box, and 2) GC box (CCGCCC)
      which is present in position 3' to TATA box. The removal of the CRE-binding
      protein by titration (by the addition of appropriate oligonucleotides to the
      incubation mixture) resulted in a decrease in transcription of the protamine
      gene. These results were confirmed by experiments in which the pure CRE-binding
      factor (TPBP1) was used, as well as by those where a stimulatory effect of cAMP
      on protamine promoter transcription was observed. On the other hand, addition of
      oligonucleotides containing the GC-box sequence enhanced the protamine gene
      transcription indicating that the protein (Sp1 like) which binds to this sequence
      acts as a repressor of protamine gene expression. These results confirm the
      previously proposed model which suggested that the GC box played a role in
      negative regulation of the protamine gene expression. Involvement of some other
      factors in this process was also discussed.

PMID- 8862183
TI  - Purification of IHF-like protein from gram-negative bacteria in one
      chromatographic step.
AB  - We describe a fast and very efficient method of purification which yields highly
      purified integration host factor-like proteins in one chromatographic step. IHF
      like proteins from Acinetobacter junii or Proteus vulgaris are each an alpha beta
      heterodimer (subunits of 10 and 11 kDa) similar to the IHF of Escherichia coli
      when analyzed by polyacrylamide gel electrophoresis. The purified IHF are able to
      bind to the same ihf sites as IHF of E. coli. The results presented confirm that
      IHF is conserved during evolution in gram-negative bacteria.

PMID- 8862184
TI  - Analysis of unstable DNA sequence in FMR1 gene in Polish families with fragile X
      syndrome.
AB  - The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from
      Polish families with fragile X syndrome in order to characterize mutations
      responsible for the disease in Poland. In all affected individuals classified on
      the basis of clinical features and expression of the fragile site at X(q27.3) a
      large expansion of the unstable sequence (full mutation) was detected. About 5%
      (2 of 43) of individuals with full mutation did not express the fragile site.
      Among normal alleles, ranging in size from 20 to 41 CGG repeats, allele with 29
      repeats was the most frequent (37%). Transmission of premutated and fully mutated
      alleles to the offspring was always associated with size increase. No change in
      repeat number was found when normal alleles were transmitted.

PMID- 8862185
TI  - Halogenated benzimidazole inhibitors of phosphorylation, in vitro and in vivo, of
      the surface acidic proteins of the yeast ribosomal 60S subunit by endogenous
      protein kinases CK-II and PK60S.
AB  - Several halogeno benzimidazoles and 2-azabenzimidazoles, previously shown to be
      relatively selective inhibitors of protein kinases CK-I and/or CK-II from various
      sources, including CK-II from yeast [Szyszka et al. (1995) Biochem. Biophys. Res.
      Commun. 208, 418-424] inhibit also the yeast ribosomal protein kinase PK60S. The
      most effective inhibitor of CK-II and PK60S was tetrabromo-2-azabenzimidazole
      ](TetraBr-2-azaBz), which was competitive with respect to ATP (and GTP in the
      case of CK-II) with Ki values of 0.7 microM for CK-II, and 0.1 microM for PK60S
      PK60S phosphorylates only three (YP1 beta', YP2 alpha) out of five polypeptides
      of pp13 kDa acidic proteins of 60S subunit phosphorylated by CK-II [Szyszka et
      al. (1995) Acta Biochim. Polon. 42, 357-362]. Accordingly, TetraBr-2-azaBz
      inhibits phosphorylation only of these polypeptides, catalysed by PK60S .
      Addition of TetraBr-2-azaBz to cultures of yeast cells, at concentrations which
      were without effect on cell growth, led to inhibition of intracellular
      phosphorylation of ribosomal acidic proteins, paralleling that observed in vitro.
      TetraBr-2-azaBz is shown to be a useful tool for studies on the intracellular
      regulation of phosphorylation of the ribosomal 60S acidic proteins, which are
      involved in formation of active ribosomes.

PMID- 8862186
TI  - Solubilization and one-step purification of mannosylphosphodolichol synthase from
      Trichoderma reesei.
AB  - Mannosylphosphodolichol synthase (MPD-synthase) (EC 2.4.1.830) catalyzing
      formation of MPD from GDPMan and dolichylphosphate (PD) has been purified from T.
      reesei cellular membranes almost to homogeneity. Selective solubilization of the
      enzyme was followed by one step purification on Phenyl-Sepharose column. SDS/
      PAGE of the purified enzyme fraction revealed the presence of a protein band of
      31 kDa corresponding to the apparent molecular mass of the MPD-synthase purified
      from S. cerevisiae [Babczinski, P. et al. (1980) Eur. J. Biochem. 105, 509-515;
      Haselbeck A. (1989) Eur. J. Biochem. 181, 663-668]. During solubilization, the
      enzyme was stabilized by the presence of a lipophilic substrate dolichylphosphate
      and phospholipids as well as by protease inhibitors. The Phenyl-Sepharose
      purified enzyme had an absolute requirement for dolichylphosphate and was
      activated by cAMP dependent protein kinase.

PMID- 8862187
TI  - The activities of superoxide dismutase, catalase, glutathione peroxidase and
      glutathione reductase in erythrocytes of rats with experimental neoplastic
      disease.
AB  - In erythrocytes of rats bearing Morris hepatoma 5123 the activities of superoxide
      dismutase, glutathione peroxidase and glutathione reductase as well as the level
      of reduced glutathione increased on the 10th day after transplantation of the
      tumor. In the second phase of the tumor growth (20 days after transplantation),
      the activities of glutathione peroxidase, glutathione reductase and the level of
      reduced glutathione in erythrocytes of the experimental animals were lower than
      in controls, whereas the activity of superoxide dismutase was at that time higher
      than in controls. On the other hand, the activity of catalase did not
      significantly differ from that found in healthy rats.

PMID- 8862188
TI  - Protective effect of pantothenic acid and related compounds against
      permeabilization of Ehrlich ascites tumour cells by digitonin.
AB  - Preincubation of Ehrlich ascites tumour cells with millimolar concentrations of
      pantothenic acid, pantothenol or pantethine, but not with homopantothenic acid,
      at 22 degrees C or 32 degrees C, but not at 0 degrees C, makes the plasma
      membrane more resistant to the damaging effect of submillimolar concentrations of
      digitonin. It is proposed that this increased resistance is due to the increased
      rate of cholesterol biosynthesis. In fact, incorporation of [14C]acetate into
      cholesterol is by 45% increased in the cells preincubated with pantothenic acid;
      this probably reflects elevation of the content of CoA in such cells [Slyshenkov,
      V.S., Rakowska, M., Moiseenok, A.G. & Wojtczak, L. (1995) Free Radical Biol. Med.
      19, 767-772].

PMID- 8862189
TI  - Aging and the respiratory system.
AB  - All the components of the respiratory system are affected by aging, though at
      different rates: i) the lung elastic recoil decreases; ii) PaO2 decreases and the
      D(A-a)O2 increases; iii) the chest wall becomes stiffer; iv) the inspiratory
      muscles loose strength; and v) the respiratory centres are less sensitive.
      Residual volume, closing volume and function residual capacity increase, whereas
      vital capacity and FEV1 progressively decrease. The flow volume curve becomes
      more convex to the volume axis at low lung volume. Whether these changes are due
      to aging or associated with aging is a matter of debate. However, the aging lung
      is more fragile in the face of respiratory and systemic diseases than the
      respiratory system of young adults. Nutrition, smoking habits and sleep-related
      disorders also affect the respiratory system. Although bronchial asthma may also
      appear in the elderly, chronic obstructive pulmonary disease is one of the most
      common respiratory diseases in advanced life and is a major cause of respiratory
      failure and ICU admission. Age in itself is not a risk factor of respiratory
      failure, but elderly patients have an increased risk of mortality for both acute
      respiratory failure (the failing lung), and exacerbated chronic ventilatory
      failure (the failing pump). Although advanced age can influence the final outcome
      of elderly patients from the intensive care unit (ICU), admission to the ICU as
      well as the institution of mechanical ventilation should not be denied on the
      basis of age alone, since the severity of illness, prior health status and
      admitting diagnosis have more weight than age in the final outcome.

PMID- 8862190
TI  - Life events and the quality of life in old age. Report from a medical-social
      intervention study.
AB  - In a board medical-social intervention study in Sweden regarding the possibility
      of postponing/preventing age-related dysfunction, changes in the subjective
      evaluation of quality of life (QL) and the experience of major life events (LE)
      were recorded in the age interval 70-76 years. Significantly more negative than
      positive LE were reported, and the most common was related to disease and death
      in the family. Children's divorce was rated as the most serious negative LE; the
      most common positive LE were travel and birth of a grandchild, but recovery from
      disease was ranked highest. Despite the predominance of negative LE, QL scores
      improved both in a representative population sample that was given support in the
      form of a medical-social intervention for 2 years, and in a control sample that
      underwent the identical systematical health surveys but received no further
      active help. As the study did not demonstrate any differences in outcome
      measurement (QL) between the supported subjects and the controls, it was not
      possible to discern whether the retained well-being could be attributed the
      intervention as was hypothesized.

PMID- 8862192
TI  - The use and effectiveness of assistive devices in an elderly urban population.
AB  - The aim of this study was to examine the type, frequency and usage rate of
      assistive devices in daily life activities in a community-based population aged
      70 and over (N = 170), as well as the particular part of the intervention trial
      which focused on un-met needs, and the usage rate and effectiveness of assistive
      devices 6 and 12 months after prescription. Among persons under 80 years of age,
      24% were users of assistive devices; in the 80 years or above group, this figure
      rose to 57%. Hygiene and mobility devices were the most common. The usage rate of
      assistive devices was 84%. The reasons for disuse were an improved health status,
      or difficulties in using the device. Sixteen percent of the study population had
      un-met needs of assistive devices. At follow-up visits, the subjects estimated a
      high degree of effectiveness when using the devices, particularly in the form of
      reduced difficulty and increment of safety, and increased capacity and ability in
      various activities. We conclude that the use of assistive devices increases with
      age, and that most of the assistive devices are used and are effective. As the
      need for assistive devices changes over time, follow-ups in the home are
      necessary. Therefore, to meet the needs of a growing elderly population,
      information about assistive technology should be supplied to both personnel in
      health care and in the social service system.

PMID- 8862191
TI  - Factors related to length of stay in a geriatric evaluation and rehabilitation
      unit.
AB  - Factors related to length of stay were examined in 295 elderly patients (mean age
      = 79.0 +/- 7.3, range 65-94; males = 75, females = 220), consecutively admitted
      to a Geriatric Evaluation and Rehabilitation Unit (GERU, P. Richiedei Hospital,
      Gussago, Brescia, Italy) over a twelve-month period (November 1, 1993-October 31,
      1994). Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS),
      Basic Activities of Daily Living (BADL), Instrumental Activities of Daily Living
      (IADL), Tinetti Scale, Prognostic Nutritional Index (PNI), number of diseases and
      number of administered drugs were evaluated. An index of Disease Severity (IDS)
      was utilized to estimate the level of comorbidity severity. Three comorbidity
      classes were thus defined: I) patients with no disease of relevant severity; II)
      patients with only one disease of relevant severity accompanied by clinically
      significant comorbidity; and III) patients with two or more relevant diseases.
      The variables associated with the length of stay proved to be classes of
      comorbidity, MMSE, dependence in BADL and IADL, Tinetti scale, and PNI. The
      association of longer length of stay with greater comorbidity was enhanced by
      impairment in gait and balance (Tinetti < 18) and malnutrition (PNI > 45). These
      data suggest that the length of stay in hospital is related to comorbidity in
      patients with conditions of physical and biomedical frailty.

PMID- 8862193
TI  - Clinical presentation of bleeding peptic ulcer in the elderly.
AB  - The aim of this study was to evaluate the characteristics and risk factors of
      bleeding peptic ulcer in elderly people. The histories of 206 consecutive
      patients (110 men and 96 women) with peptic ulcer were examined from hospital
      records. The ulcer was confirmed by endoscopy, surgery or autopsy. Clinical
      parameters were compared in different age groups. The mean age of the patients
      with bleeding ulcer (N = 105) was 65.5 years compared to 57.1 years in those
      without bleeding (N = 101) (p = 0.0001). In the univariate analysis, the duration
      of symptoms was shorter than seven days in 84% of bleeders compared to 40% of non
      bleeders (p = 0.0001). Ninety percent of the bleeding patients were painfree,
      compared to 23% of patients without bleeding (p = 0.0001). Even when patients
      using nonsteroidal anti-inflammatory drugs (NSAIDs) were excluded, short duration
      of symptoms as well as absence of epigastric pain were significantly associated
      with bleeding. The bleeders tended to use more NSAIDs than non-bleeders, but the
      difference was significantly only in patients who had used NSAIDs for 30 or fewer
      days. Atypically located as well as giant ulcers bled more often than typically
      situated ulcers or smaller ulcers. In the logistic regression analysis, advanced
      age, short duration of symptoms and absence of epigastric pain independently
      predicted bleeding of peptic ulcer. In conclusion, although bleeding is a
      complication of peptic ulcer, it can also be considered a variant type of ulcer
      with specific characteristics. Old age seems to be an independent risk factor for
      bleeding, but it has no effect on the clinical presentation of the disease.

PMID- 8862194
TI  - A population-based study on the association between dementia and hip fractures in
      85-year olds.
AB  - The association between dementia and hip fracture was studied in a representative
      sample of 85-year olds (N = 485). The diagnosis of dementia was made according to
      the DSM-III-R. The prevalence of hip fracture was obtained by history and
      inspection of the hip. Bone mineral density was measured with dual photon
      absorptiometry of the right calcaneus. Hip fracture was associated with both
      Alzheimer's disease (p < 0.01) and vascular dementia (p < 0.01) in women, but not
      in men. Among women with dementia, the rate of hip fracture was more than twice
      that found in the general population (32.7% vs 13.6%). Bone density was not
      associated with dementia or hip fracture. Body mass index and body weight were
      lower in women with dementia and in women with hip fracture. The prevalence of
      hip fracture was also increased in subjects who used psychotropic drugs,
      especially tricyclic antidepressants. A logistic multiple regression analysis
      showed that dementia, use of antidepressants and gender independently contributed
      to hip fracture. The reason why subjects with dementia are at increased risk for
      hip fractures may be that these subjects have a defective neuromuscular
      regulation, gait apraxia, use more antidepressants, and have a lower body mass
      index. Another explanation of the association may be that surgery and anesthesia
      give rise to systemic hypotension that leads to cerebral hypoperfusion and
      ischemic and neuronal death in vulnerable brain areas, and as a consequence may
      lead to dementia or worsen the symptoms in subjects already affected by dementia.

PMID- 8862195
TI  - Age and sex differences in body size and composition during rhesus monkey
      adulthood.
AB  - Body size and composition were measured in forty-one adult Rhesus monkeys (Macaca
      mulatta) in order to characterize changes that occur during later life for both
      genders. Data were obtained by traditional somatometric techniques and by dual
      energy X-ray absorptiometry. Representative monkeys were chosen within six
      categories defined by age (Young Adult, 6-9 year-old; Middle Aged, 15-19 year
      old; Older Adult, 26-30 year-old), and sex. Body weight and most external
      measures of body size were greater during middle age and later life than in young
      adulthood, as were body fat content and lean body mass. Females tended to have a
      higher percentage body fat than males in all age categories. Lean tissue mass was
      markedly greater in the two younger groups for both sexes, compared to older
      adults. Bone mineral content and density were higher in the males than the
      females, but differences in bone mineralization among age groups did not achieve
      statistical significance. Such data derived from adult nonhuman primates are
      useful for defining fundamental biological changes with age in these species, and
      have value as a comparative model for studies of human aging and age-related
      morbidity.

PMID- 8862196
TI  - A district-wide examination of 75-year olds suggests discrimination in the
      provision of services.
AB  - The aim of this study was to assess the adequacy of existing services across a
      whole health district for those aged 75 years, in an attempt to detect shortfalls
      and biases in the provision of services. This study was carried out as a cross
      sectional survey using community based nurses in the county of South Glamorgan.
      1376 people in their 75th year who were registered with a general practitioner
      were visited, and their problems assessed by community based nurses. There was a
      marked difference in the results of the assessment for different services. It was
      estimated that 76% of the 75-year olds would benefit from additional health
      services, and 37% from social services. There was a striking difference between
      the services in the proportion of people whose problems were satisfactorily
      solved, according to the criteria used by the community nurses. The proportion of
      problems that were solved varied according to the degree of dependency of the
      individuals, and the service involved. Some services showed a clear trend to care
      more for dependent people; services with a relatively undeveloped home delivery
      system seemed likely to discriminate against people who were dependent.

PMID- 8862197
TI  - A simple program to train case managers in community elderly care.
AB  - The case manager, like many "new professions" does not yet have a defined
      curriculum. We consider that the principal requisite for case managers is a
      proficient knowledge of assessment for the care of elderly. Therefore, we focused
      a four-week teaching course for future case managers on the National Resident
      Assessment Instrument (RAI) of the United States and the Long-Term Care Program
      Application and Admission Form of British Columbia, Canada. We verified that this
      simple program provides students with adequate skills to become case managers.

PMID- 8862199
TI  - Pertussis overlooked as cause of cough in adults.

PMID- 8862198
TI  - Meropenem marketed for meningitis, intra-abdominal infection.

PMID- 8862200
TI  - Tobacco, alcohol, and drug use increasing among women.

PMID- 8862201
TI  - Empowering patients by promoting self-care.

PMID- 8862202
TI  - Pain management for bone metastases.

PMID- 8862203
TI  - Harvey A. K. Whitney Lecture. Searching for the soul of pharmacy.
AB  - This lecture explores the theme that the soul (character) of individual
      pharmacists must be nourished in order to save pharmacy as a health profession.
      Health care is being drastically altered by a private sector that says it wants
      to lower health care costs but in fact desires huge profits. Pharmacy leaders
      have shown nimbleness in dealing with corporate demands, but many are becoming
      too preoccupied with the business of health care. Pharmacists need to discipline
      themselves lest the lure of the new order blind them to their primary obligations
      to patients. Pharmacists should act as a counterforce to the marketing of
      prescription drug products directly to consumers. Pharmacy is an occupation
      psychically bound to the act of providing medications to patients, but which
      knows it must find a new reason for being. There is hope for the profession in
      this realization--it led to the philosophy of pharmaceutical care--but no
      guarantees. Pharmacists must declare that their interests may differ from their
      employers' whenever patient welfare is in question. Suggestions are offered on
      how to nourish the soul of pharmacy.

PMID- 8862204
TI  - Bisphosphonates for controlling pain from metastatic bone disease.
AB  - The rationale for and efficacy of bisphosphonates for pain due to cancer that has
      metastasized to bone are reviewed. Typical strategies for controlling metastatic
      bone pain have consisted of opioids, nonsteroidal anti-inflammatory drugs,
      surgery to stabilize bone, cancer chemotherapy, radiation therapy, and
      radiopharmaceuticals. Cancer metastasis to bone can produce pain through the
      release of prostaglandins, bradykinin, substance P, and histamine; growth of
      tumor into surrounding tissue; stretching of the periosteum; and pathological
      fractures. It has been suggested that bisphosphonates can benefit these patients
      by decreasing the amount of pain or decreasing analgesic requirements.
      Bisphosphonates bind to hydroxyapatite crystals, making it more difficult for
      osteoclasts to recognize exposed unmineralized bone surfaces, and are directly
      toxic to osteoclasts. Etidronate disodium, pamidronate disodium, clodronate
      disodium, and alendronate sodium are bisphosphonates that have been studied in
      patients with painful bone metastases. Although each of these has shown at least
      some benefit, the most promising agent appears to be pamidronate, especially the
      i.v. formulation given monthly. Although oral formulations of this agent have
      been studied, poor bioavailability and adverse effects limit their usefulness.
      Adverse effects of bisphosphonates include GI reactions, impairment of renal
      function, anemia, and electrolyte abnormalities. Bisphosphonates are of some
      benefit in relieving metastatic bone pain, but the exact role, agent, route, and
      duration are issues that need further study.

PMID- 8862205
TI  - Work redesign and role restructuring in a pharmacy department with pharmacist
      assistants.
AB  - A new staffing model for decentralized pharmacists and support staff at a
      university hospital is described. A new technical support position--the
      pharmacist assistant--was created, and activities were reallocated among the
      pharmacists, pharmacist assistants, and pharmacy technicians according to the
      recommendations of two total quality management teams. Pharmacist assistants were
      to perform many of the drug distribution and record-keeping functions previously
      performed by pharmacists. The activities marked for reallocation accounted for
      about 50% of pharmacist time in the existing staffing model; they would not be
      performed by experienced pharmacy technicians who received brief training to be
      pharmacist assistants. Nine pharmacists and nine technicians tested the new
      staffing model on four patient care units over a four-week period. The
      reassignment of pharmacist tasks to pharmacist assistants theoretically gave
      pilot-unit pharmacists more time for providing and documenting patient-specific
      clinical activities and an additional 12 hours a week to participate in such
      global patient care activities as critical-pathway and quality improvement
      meetings. By the end of the study, the pharmacist assistants demonstrated that
      they could perform the reassigned activities; however, the pharmacists were not
      yet confident in the assistants' ability to do so. A pilot study of a new
      decentralized pharmacy staffing model demonstrated that technical support
      personnel can perform many distributive and record-keeping activities
      traditionally performed by decentralized pharmacists.

PMID- 8862206
TI  - Psychosocial and demographic predictors of pediatric psychotropic medication use.
AB  - The effects of age, gender, and family background on children's use of
      prescription psychoactive medications were studied. Patient and prescribing
      information was obtained for children enrolled as dependents in any of five
      prescription drug benefit plans during the period from December 29, 1992, through
      December 28, 1993. A binary response model was specified under the assumption of
      logistic distribution of probabilities of psychotropic drug use. The independent
      variables were family size, parenting type (single- or two-parent family),
      parental use of psychotropic medications, and child's age, gender, and the
      interaction between age and gender. Logistic regression analysis was conducted
      not only for overall psychotropic drug use but also for antidepressants,
      antianxiety drugs, and CNS stimulants. The sample included 3144 children; 3.9%
      received psychotropic drugs. Family size and parenting type had no effect on
      overall use of psychotropic drugs by children, but children were more likely to
      receive psychotropic drugs if the parents took them. The study showed an
      interaction between age and gender. At younger ages, boys were more likely than
      girls to receive psychotropic drugs; the opposite was true at older ages. For
      particular subcategories of drugs the study showed that (1) boys were more likely
      than girls, and young children were more likely than older children, to receive
      CNS stimulants, (2) children from single-parent families were less likely to use
      antidepressants than children from two-parent households, and (3) the influence
      of mothers' psychotropic drug use extended to all three drug classes, but the
      influence of fathers' psychotropic drug use existed for antidepressants only. The
      effects of demographic and familial factors on children's use of psychotropic
      drugs varied according to the drug class.

PMID- 8862207
TI  - Stability of cidofovir in 0.9% sodium chloride injection and in 5% dextrose
      injection.
AB  - The stability of cidofovir in i.v. admixtures under refrigerator and room
      temperature conditions was studied. Admixtures of cidofovir 0.21 and 8.12 mg/mL
      in 0.9% sodium chloride injection or 5% dextrose injection and of 0.085 and 3.51
      mg/mL in 5% dextrose and 0.45% sodium chloride injection were prepared in
      triplicate in polyvinyl chloride (PVC) or polyethylene-polypropylene containers
      and i.v. administration sets and stored for 24 hours at 2-8 or 30 degrees C. The
      lower concentration of cidofovir corresponded to an assumed dose of 0.5 mg/kg for
      a 40-kg patient, and the higher concentration to an assumed dose of 10 mg/kg for
      a 100-kg patient. Samples were removed at 0 and 24 hours and analyzed for
      cidofovir concentration by high-performance liquid chromatography. Physical
      compatibility was also studied. The stability of cidofovir in 0.9% sodium
      chloride injection and in 5% dextrose injection at low- and high-dose
      concentrations was unaffected by storage at either temperature. All admixtures
      were clear, colorless, and free of visible particles or precipitation. There were
      no substantial changes in pH or number of particles of > or = 10 microns in
      diameter. Cidofovir 0.21 and 0.12 mg/mL was stable in 0.9% sodium chloride
      injection and 5% dextrose injection in PVC and polyethylene-polypropylene
      containers and i.v. administration sets for up to 24 hours at 2-8 and 30 degrees
      C. Cidofovir was compatible with the injectable solutions studied.

PMID- 8862208
TI  - Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and
      flucytosine in extemporaneously compounded oral liquids.
AB  - The stability of drugs commonly prescribed for use in oral liquid dosage forms
      but not commercially available as such was studied. Acetazolamide 25 mg/mL,
      allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and
      flucytosine 10 mg/mL were prepared in 1:1 mixture of Ora-Sweet and Ora-Plus
      (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock
      Laboratories), and cherry syrup and placed in polyethylene terephthalate bottles.
      The sources of the drugs were capsules and tablets. Six bottles were prepared per
      liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the
      dark. A sample was removed from each bottle initially and at intervals up to 60
      days and analyzed for drug concentration by stability-indicating high-performance
      liquid chromatography. At least 94% of the initial drug concentration was
      retained in all the oral liquids for up to 60 days. There were no substantial
      changes in the appearance or odor of the liquids, or in the pH. Acetazolamide 25
      mg/mL, allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and
      flucytosine 10 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three
      extemporaneously compounded oral liquids.

PMID- 8862209
TI  - Pharmacy involvement in and use of critical pathways in Minnesota hospitals.

PMID- 8862210
TI  - ASHP guidelines on medication-use evaluation. American Society of Health-system
      Pharmacists.

PMID- 8862211
TI  - Prudent selection of antimicrobials for neonatal sepsis.

PMID- 8862212
TI  - Administering itraconazole via nasogastric tube.

PMID- 8862213
TI  - Reminder of danger from chewing extended-release products.

PMID- 8862214
TI  - Serum versus plasma in ophthalmic solutions.

PMID- 8862215
TI  - Additional information on using clozapine in adults.

PMID- 8862216
TI  - Assessing medication adherence by pill count and electronic monitoring in the
      African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.
AB  - The Medication Event Monitoring System (MEMS), an electronic monitor which
      records the date and time of bottle cap openings, and pill counts were used to
      assess patterns of adherence for the primary antihypertensive drug in the African
      American Study of Kidney Disease and Hypertension Pilot Study (AASK). Blacks with
      hypertension and moderately reduced renal function were randomized to one of two
      levels of blood pressure control and to one of three antihypertensive drug
      regimens: primary therapy with a calcium channel blocker, an angiotension
      converting enzyme inhibitor, or a beta-blocker. Of the 94 participants in AASK,
      91 had MEMS recordings and pill counts for 313 regularly scheduled monthly follow
      up visits. The average length of follow-up was 4.6 months. An acceptable level of
      adherence by pill count was achieved if 80% to 100% of the prescribed pills were
      not returned to the clinic. Adherence by MEMS to a once-a-day drug dosing
      schedule was acceptable if 80% of the time intervals between MEMS openings were
      within 24 +/- 6 h. Acceptable adherence by pill count was observed at 68% of the
      follow-up visits; MEMS indicated nonadherence at 47% of those visits. Blood
      pressure was within goal in 50% of the participants who were adherent by both
      pill count and MEMS throughout their follow-up visits, and only 14% of the
      participants who were identified nonadherent by one or both methods. These
      findings suggest that electronic monitoring is a useful adjunct to pill counts in
      assessing adherence to antihypertensive drugs. Feedback of electronically
      collected information on dosing intervals to participants and staff may enhance
      adherence.

PMID- 8862217
TI  - Predominance of nocturnal sympathetic nervous activity in salt-sensitive
      normotensive subjects.
AB  - To assess the relation between salt sensitivity and autonomic nervous function by
      power spectral analysis of heart rate variability in normotensive subjects, low
      and high salt diets were given to 13 normotensive men (aged 25 to 39 years) for 4
      days each. Autonomic function was assessed by power spectral analysis of R-R
      intervals based on an autoregressive algorithm from 24-h Holter
      electrocardiogram. Subjects whose mean blood pressure was increased more than 3
      mm Hg by high salt diet were defined as salt sensitive (SS, n = 5), and the
      remainder as salt resistant (SR, n = 8). Using the low frequency (LF, 0.1 Hz) and
      high frequency (HF, 0.25 Hz) components, the LF to total power ratio (%LF) was
      used as a marker of sympathetic activity, and the HF to total power ratio (%HF)
      as a marker of parasympathetic activity. Compared to the daytime, SR revealed a
      decrease in %LF and an increase in %HF during the night on both diets. In SS,
      these circadian changes were observed only during low-salt diet. During the
      night, SS showed a higher %LF and a lower %HF than SR. Plasma catecholamines
      tended to be decreased by the high sodium diet in SR but not in SS subjects.
      These results suggest that the persistent nocturnal predominance of sympathetic
      nervous activity in a salt-sensitive men may contribute to the subsequent
      increase of blood pressure in these subjects.

PMID- 8862218
TI  - Hyperinsulinemia, family history of hypertension, and essential hypertension.
AB  - The aim of this study was the evaluation of the relationships among
      hyperinsulinemia, a family history of hypertension, and essential hypertension.
      Insulin and C-peptide responses to an oral glucose load were studied in 175 lean
      normotensives (N) and untreated hypertensives (H) with (F+) and without (F-) a
      family history of hypertension: 30 NF-, 30 NF+, 45 HF-, and 70 HF+. The groups
      were comparable for age, sex, body mass index, and blood pressure. The following
      parameters were evaluated: plasma glucose (G), serum insulin (I), and C-peptide
      (Cp) before and 30, 60, 90, and 120 min after the glucose load, fasting
      glucose/insulin ratio (ISI), fasting insulin/C-peptide ratio (I/Cp), and 24-h
      ambulatory blood pressure monitoring. Plasma glucose was measured, fasting and
      during the test, and it and I/Cp were similar in the four groups. Serum insulin
      and Cp, both fasting and stimulated, were significantly higher and ISI lower in
      normotensives and hypertensives with hypertensive parents. Grouping the subjects
      first on the basis of blood pressure and then on the basis of family history, no
      differences were found between normotensives and hypertensives, whereas I and Cp,
      fasting and stimulated, were significantly higher and ISI lower in subjects with
      positive as compared to negative family history. The closest correlations between
      insulin and ambulatory blood pressure were found in normotensive with
      hypertensive parents; in hypertensives with hypertensive parents we only found a
      direct correlation between fasting Cp and nocturnal blood pressure fall; in
      hypertensives with normotensive parents insulin inversely correlated with
      nocturnal blood pressure fall. Insulin resistance seems to have a familial basis,
      independently of the presence of hypertension. Instead of showing a causal
      relationship between insulin resistance and hypertension, our results indicate
      that the two are partly independent components of a common familial pattern.

PMID- 8862219
TI  - Differences in insulin and sympathetic responses to glucose ingestion due to
      family history of hypertension.
AB  - To evaluate the relationship of metabolic and neural factors in familial
      hypertension, we examined blood pressure (BP), blood glucose, and plasma insulin
      and norepinephrine (NE) levels before and every 30 min for 120 min after glucose
      ingestion in six groups with 20 subjects each: normotensive subjects (NT) with
      and without a family history of hypertension; borderline hypertensive patients
      (BHT) with and without a family history of hypertension; and established
      hypertensive patients (EH) with and without a family history of hypertension. The
      changes in blood glucose were similar in the six groups. In the subjects with a
      positive family history of hypertension regardless of BP levels, the basal levels
      and changes in insulin levels after glucose ingestion were significantly greater
      than those in the subjects without a family history of hypertension (F = 13.32, P
      = .0001). In BHT and EH subjects, regardless of family history, changes in
      insulin were greater than in NT (F = 16.00, P = .0001). Basal levels and changes
      in plasma NE were higher in BHT and EH (F = 26.55, P = .0001) than NT and changes
      in plasma NE were greater in subjects with a family history than those in
      subjects without a family history (F = 18.32, P = .0001). Thus, abnormal insulin
      and NE responses to glucose appear to aggregate in subjects with a history of
      familial hypertension, regardless of the level of BP. Furthermore, the ratio of
      delta NE/ delta insulin (changes from basal to peak) in NT and BHT, and in
      subjects with a family history were significantly greater than in EH and in
      subjects without a family history. Thus, we demonstrated that concomitant
      abnormalities in the glucose-insulin regulatory system and the sympathetic
      nervous system characterize the early phase in the development of hypertension
      and these abnormalities have an apparent genetic basis.

PMID- 8862220
TI  - Effect of insulin on renal sodium and uric acid handling in essential
      hypertension.
AB  - In normal subjects, insulin decreases the urinary excretion of sodium, potassium,
      and uric acid. We tested whether these renal effects of insulin are altered in
      insulin resistant hypertension. In 37 patients with essential hypertension, we
      measured the changes in urinary excretion of sodium, potassium, and uric acid in
      response to physiological euglycemic hyperinsulinemia (by using the insulin clamp
      technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate
      averaged 26.6 +/- 1.5 mumol/min/kg, i.e., 20% lower than in normotensive controls
      (33.1 +/- 2.1 mumol/min/kg, P = .015) In the basal state, fasting plasma uric
      acid concentrations were higher in men than women (P < .001), were positively
      related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P <
      .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related
      to HDL cholesterol concentrations (r = -0.59, P = .0001) and glucose disposal
      rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely
      related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P <
      .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related
      to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood
      pressure, plasma uric acid and sodium concentration, and creatinine clearance did
      not change. In contrast, hyperinsulinemia caused a significant decrease in the
      urinary excretion of uric acid (2.67 +/- 0.12 to 1.86 +/- .14 mumol/min/1.73 m2,
      P = .0001), sodium (184 +/- 12 to 137 +/- 14 mumol/min/1.73 m2, P = .0001), and
      potassium (81 +/- 7 to 48 +/- 4 mumol/ min/1.73 m2, P = .0001). Both in absolute
      terms (clearance and fractional excretion rates) and percentagewise, these
      changes were similar to those found in normotensive subjects. Insulin-induced
      changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective
      changes in sodium excretion. In hypertensive patients, higher uric acid levels
      and lower renal urate clearance rates cluster with insulin resistance and
      dyslipidemia. Despite insulin resistance of glucose metabolism, acute
      physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and
      antiuricosuria in these patients.

PMID- 8862221
TI  - Effects of chronic hypertension and left ventricular hypertrophy on the extent of
      infarct expansion in rats.
AB  - Left ventricular hypertrophy is an adaptive response to long standing
      hypertension. However, the influence of left ventricular hypertrophy with
      hypertension on extent of infarct expansion has not been studied. We compared the
      effects of left ventricular hypertrophy with hypertension on infarct expansion in
      spontaneously hypertensive rats (SHR, n = 76), Wistar-Kyoto rats (WKY; n = 46)
      and spontaneously hypertensive rats treated with delapril, an angiotensin
      converting enzyme (ACE) inhibitor (SHRD; n = 39). The survival rates at 7 days
      after myocardial infarction were 41%, 24%, and 46% for WKY, SHR, and SHRD. The
      survival rate of SHR was significantly lower than those of both SHRD and WKY (P <
      .05). In the surviving rats (18 SHR, 19 WKY, 18 SHRD), both left ventricular
      cavity area (LCVA) and the infarct segment length per the noninfarct segment
      length (FW/IVS), measured as indices of left ventricular dilation, were
      significantly less in SHR and SHRD than in WKY, and the thickness of the left
      ventricular free wall (Wth), used as an index of left ventricular thinning, was
      significantly higher in both SHR and SHRD than in WKY (P < .01). However, there
      was no significant difference in FW/IVS, LCVA, and Wth between SHR and SHRD.
      Hemodynamic findings 1 week after coronary occlusion demonstrated that all rats
      were in heart failure, and there were no significant differences in hemodynamics
      among the three groups. In conclusion, our findings showed that hypertrophy with
      hypertension reduced infarct expansion, but that reduction of blood pressure by
      ACE inhibitor did not reduce infarct expansion more than hypertrophy did.
      However, this finding suggest that an ACE inhibitor may improve the rate of
      survival of patients with left ventricular hypertrophy with hypertension.

PMID- 8862222
TI  - Mechanisms of orthostatic hypotension and tachycardia in patients with
      pheochromocytoma.
AB  - We have explored the pathophysiological mechanisms of orthostatic hypotension and
      orthostatic tachycardia, found to be present in 83% and 61% respectively of 18
      patients with subsequently proven pheochromocytoma. Orthostatic increases in
      plasma norepinephrine (NE) concentrations were significantly greater in the
      patients than in normal control subjects. Intravenous infusions of NE at 1, 2, 4,
      8, and 16 micrograms/min induced similar increases in plasma NE levels but
      smaller increments in systolic and diastolic BP in the pheochromocytoma patients
      than in normal control subjects. This was reflected by a significantly greater
      increment in plasma NE concentration required to raise systolic BP by 15 mm Hg
      and diastolic BP by 7 mm Hg in the pheochromocytoma patients than in the normal
      subjects (P < .05 and P < .01, respectively). Measurements of venous contractile
      responses to locally infused NE by the dorsal hand vein (LVDT) technique revealed
      significantly reduced slopes of the regressions of log NE infusion rate on change
      in venous diameter in the pheochromocytoma patients compared with normal
      subjects. The results indicate reduced responsiveness of the vasculature to NE in
      patients with pheochromocytoma, probably due to down-regulation of alpha
      adrenergic receptors resulting from persistent elevation of the physiological
      agonist NE. This was shown by other authors to be present in circulating
      platelets. The pathophysiological importance of the subnormal venous responses to
      the orthostatic hypotension and tachycardia in the patients were supported by the
      finding that the orthostatic changes were corrected by lower body compression to
      45 mm Hg with a MAST pressure suit.

PMID- 8862223
TI  - Urinary albumin excretion--a predictor of risk of cardiovascular disease. A
      prospective 10-year follow-up of middle-aged nondiabetic normal and hypertensive
      men.
AB  - To study how the risk of cardiovascular disease changes with increasing levels of
      urinary albumin excretion (UAE), we prospectively studied a random sample of 120
      49-year-old men with a wide range of blood pressures. Based on diastolic blood
      pressure (DBP), the subjects were divided into normotensives (DBP < 90 mm Hg; n =
      21), borderline hypertensives (DBP 90 to 94 mm Hg; n = 30), mild hypertensives
      (DBP 95 to 104 mm Hg; n = 45) and moderate to severe hypertensives (DBP > 105 mm
      Hg; n = 24). None had been previously treated for hypertension or had secondary
      hypertension, diabetes mellitus, or other cardiovascular diseases at baseline.
      Heart and kidney function and metabolic and hormonal variables were with beta
      blockade, diuretics, or hydralazine. The cardiovascular morbidity during 10 years
      of follow-up was studied. The hypertensives were treated with beta-blockade,
      diuretics, or hydralazine. The cardiovascular morbidity during 10 years of follow
      up was studied. The 19 subjects who developed cardiovascular disease had
      significantly higher baseline UAE than the group that did not (median value 16.6
      mg/24 h; range 3.5 to 73, and 9.7 mg/24 h, range 0 to 308, respectively). UAE
      correlated to systolic blood pressure (P = .0115) and DBP (P = .031), but not to
      smoking behavior or serum cholesterol. The risk of cardiovascular disease was
      associated with UAE and smoking independently of blood pressure (P = .001 and P =
      .015, respectively), and the risk increased continuously with increasing UAE. The
      initial UAE thus emerged as an efficient and independent predictor of
      cardiovascular disease in middle-aged hypertensive and normotensive men. UAE
      appeared to be a stronger predictor than blood pressure and serum cholesterol.

PMID- 8862224
TI  - The relationship between renal cortical volume and predisposition to
      hypertension.
AB  - It has been proposed that a reduction in the number of nephrons is a renal
      abnormality that plays an important role in the pathogenesis of essential
      hypertension. The objective of this study was to determine whether renal cortical
      volume, used as a measure of the number of nephrons, is lower in normotensive
      subjects with a familial predisposition to develop essential hypertension than in
      subjects who lack this predisposition. For this purpose, we measured renal
      cortical volume using electron beam computed tomography in 26 white offspring to
      two hypertensive parents (OHT; 14 women, 12 men) and 27 white offspring of two
      normotensive parents (ONT; 13 women, 14 men) who were stabilized on a high sodium
      diet for 3 days (200 mmol/day). In women, mean age was significantly greater in
      OHT than ONT (46.1 +/- 4.9 [standard deviation] v 41.8 +/- 5.1 years,
      respectively, P = .04)In men, means for age and weight were greater in OHT than
      ONT (age: 47.1 +/- 7.7 v 37.9 +/- 8.1 years, P < .01; weight: 90.2 +/- 10.7 v
      81.1 +/- 9.4 kg, P = .03.) In women, mean total cortical volume did not differ
      significantly between OHT and ONT (156 +/- 33.3 v 166 +/- 30.9 cc, P = .80).
      After adjustment for interindividual differences in age, mean total cortical
      volume remained not significantly different in OHT than ONT (160 +/- 29.0 v 162
      +/- 32.4 cc, P = .83). In men, mean total cortical volume was significantly
      greater in OHT than ONT (210 +/- 33.6 v 180 +/- 20.0 cc, P = .01). After
      adjustment for interindividual differences in age, mean total cortical volume
      remained significantly greater in OHT than ONT (207 +/- 33.2 v 182 +/- 19.8 cc, P
      = .02). After adjustment for interindividual differences in body weight, mean
      total cortical volume did not differ significantly between OHT and ONT (201 +/-
      21.7 v 187 +/- 20. cc, P = .09). The results of this study do not support the
      hypothesis that a decrease in renal cortical volume, as a result of a decrease in
      number of nephrons, is a characteristic of white women or men with a familial
      predisposition to develop essential hypertension.

PMID- 8862225
TI  - Relationship between birth weight and awake blood pressure in children and
      adolescents in absence of intrauterine growth retardation.
AB  - This study was designed to examine the relationship between birth weight (BW) and
      ambulatory blood pressure in children and adolescents, born at term in absence of
      intrauterine growth retardation. Twenty-four hour ambulatory blood pressure
      monitoring (ABPM) was performed on 332 children (150 boys), aged from 6 to 16
      years. Subjects were stratified by BW tertiles and age. ABPM was performed using
      SpaceLabs 90207 monitor during a regular school day. Blood pressure (BP) was
      measured every 20 min from 06:00 to 24:00, and thereafter every 30 min. Means of
      systolic BP (SBP) and diastolic BP (DBP) during 24 h, daytime (08:00 to 22:00),
      and nighttime (24:00 to 06:00) were calculated. Systolic and diastolic load was
      estimated as the percentage of measurements above the age- and sex-specific 95th
      percentile during the 24 h. BW was inversely related to daytime (SBP (P = .04)
      and SBP load (P = .04) when controlled for sex, current height, ponderal index
      (weight/height3), and age. The predictive values of daytime SBP throughout the
      pediatric age group in the two extreme tertiles of BW (lowest, 2.500 to 3.200 kg;
      and highest, 3.501 to 4.820 kg) were obtained from regression equations including
      SBP during activity period or SBP load and age. Children who had lower BW tended
      to have higher daytime SBP or SBP load at any age although this difference was
      not statistically significant. These differences became more evident as the
      subjects got older. BW is a determinant of daytime SBP even in the absence of
      intrauterine growth retardation. The influence of BW seems to increase with age.

PMID- 8862226
TI  - Renal and antihypertensive effects of neutral endopeptidase inhibition in
      transgenic rats with an extra renin gene.
AB  - The cardiovascular consequences of neutral endopeptidase (NEP) inhibition with
      the NEP inhibitor ecadotril were evaluated by determining acute and long-term
      effects of the compound on hemodynamic, hormonal, renal, and structural
      parameters in hypertensive transgenic rats harboring a mouse renin gene (TGR
      (m(Ren2)27) and in normotensive controls (Sprague-Dawley rats, SDR). Acute
      administration of ecadotril (10 and 30 mg/kg, orally) produced a dose-dependent
      decrease in systolic blood pressure with a maximal effect of -23 mm Hg between 2
      and 4 h after oral administration. The NEP activity in plasma was significantly
      inhibited and the plasma levels of atrial (ANP) and brain (BNP) natriuretic
      peptides and their second messenger, cyclic GMP, were distinctly raised after
      oral administration. In addition, ecadotril (10 and 30 mg/kg, orally) produced a
      dose-dependent increase in the urinary excretion of sodium and cyclic GMP. These
      effects were more pronounced in TGR (mRen2)27 than in the normotensive SDR
      without an activated natriuretic peptide system. In the long-term study, the
      systolic pressure in control TG (m(Ren2)27) rats increased from 213 +/- 5 to 255
      +/- 7 mm Hg, whereas, in animals treated with ecadotril (30 mg/kg, orally twice
      daily), the blood pressure increased only from 213 +/- 5 to 227 +/- 6 mm Hg
      during the observation period of 13 weeks. The increases in heart weight and in
      kidney weight were also delayed. At the end of the study, cyclic GMP was elevated
      and ANP tended to be higher, whereas plasma renin activity had decreased. These
      data indicate a beneficial pharmacological profile of neutral endopeptidase
      inhibition that could prove useful in the treatment of cardiovascular diseases
      like hypertension.

PMID- 8862228
TI  - Platelet calcium handling is different in rats with salt-dependent and
      spontaneous forms of genetic hypertension.
AB  - Increased platelet cytosolic free calcium concentration ([Ca2+]i) has been
      demonstrated in both human essential hypertension and spontaneous hypertension of
      the rat. The present study was designed to extend the investigation on platelet
      Ca2+ handling to two models of salt-dependent genetic hypertension (Sabra and
      Dahl rat strains). No major [Ca2+]i elevation was seen in salt hypertensive SBH
      Sabra or SS/Jr Dahl rats. This contrasts with the data obtained in Lyon
      hypertensive rats (a spontaneous form of genetic hypertension) in which basal
      platelet [Ca2+]i was clearly increased and correlated positively with diastolic
      blood pressure. In these two strains, basal platelet [Ca2+]i correlated with
      pulse pressure but not with diastolic pressure. The absence of a significant
      relationship between platelet [Ca2+]i and diastolic pressure in both Sabra and
      Dahl rats indicates that, at least in young rats with developing salt
      hypertension, platelet cytosolic calcium need not reflect calcium changes
      occurring in the vascular smooth muscle or resistance arterioles. In contrast to
      the high values seen in Lyon hypertensive rats, the [Ca2+]i rise induced by
      thrombin was unchanged in salt-sensitive SS/Jr Dahl rats and substantially
      reduced in hypertension-prone SBH rats (irrespective of salt intake). The initial
      rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels was
      similar in SBN and SBH as well as in SR/Jr and SS/Jr rats kept on a low-salt diet
      but was reduced by high salt intake in platelets of salt-resistant (SBN and
      SR/Jr) animals only. Since platelets of Lyon hypertensive rats are also
      characterized by greater initial rate of thrombin-induced Mn2+ entry, this
      parameter was always higher in rats with established hypertension compared to
      their respective normotensive controls. Our study demonstrated that alterations
      of platelet Ca2+ handling are different in salt-dependent than in spontaneous
      forms of genetic hypertension.

PMID- 8862227
TI  - Renal and vascular effects of chronic endothelin receptor antagonism in malignant
      hypertensive rats.
AB  - The effect of the combined ETA/ETB endothelin receptor antagonist bosentan on
      blood pressure, vascular hypertrophy, and pathologic renal changes was
      investigated in a model of malignant hypertension, severe vascular hypertrophy,
      and enhanced vascular expression of endothelin-1, the deoxycorticosterone acetate
      (DOCA), and salt-treated spontaneously hypertensive rat (SHR). DOCA-salt treated
      SHR received 100 mg bosentan per kilogram weight per day mixed with their food.
      Systolic blood pressure of untreated DOCA-salt SHR rose to 241 +/- 1.5 mm Hg,
      whereas that of bosentan-treated rats rose to 221 +/- 5.1 mm Hg (P < .01).
      Cardiac and conduit artery mass were not affected by treatment. Small arteries
      from the coronary, renal, and mesenteric circulations showed a smaller media
      width and cross-sectional area of the media in rats treated with bosentan than in
      untreated rats. The kidneys showed the presence of fibrinoid necrosis in a high
      percentage of afferent arterioles and glomeruli of untreated DOCA-SHR. Some
      kidneys of treated rats exhibited less severe vascular hypertrophy and lesser
      extent of vascular or glomerular fibrinoid necrosis, but the renal injury score
      of bosentan-treated DOCA-SHR was only at the limit of significance from that of
      untreated rats (P = .06). These results suggest a role for endothelin-1 in blood
      pressure elevation and the severe vascular hypertrophy of small arteries of the
      coronary, renal, and mesenteric vasculature, but not of the heart or larger
      conduit vessels in the malignant hypertension that SHR develop after treatment
      with DOCA and salt. Although some bosentan-treated rats showed fewer renal
      lesions, a significant effect on renal pathology could not be unambiguously
      demonstrated. Further studies will be necessary to determine whether endothelin
      antagonists may indeed offer some degree of renal protection and have therapeutic
      potential in severe or malignant hypertension.

PMID- 8862229
TI  - Neither physical exercise nor alpha 1- and beta-adrenergic blockade affect plasma
      endothelin concentrations.
AB  - Endothelins (ET) are recently discovered vasoconstrictor agents released from
      endothelial cells and have been the object of intense investigation by
      researchers. Many of the factors that seem to influence the release of ET are
      modified by prolonged exercise. The purpose of this study was to investigate the
      effect of physical exercise on ET plasma concentrations and the effect of alpha-
      and beta-blockade on ET concentrations at rest and during exercise. Fifteen young
      volunteers (age 20-35 years) performed an exercise test on a bicycle ergometer.
      The starting workload of 50 W was increased by 30 W every 3 min until maximal
      heart rate was achieved; after a 2 min recovery period at 50 W the test continued
      for 15 min at 60% maximal work load. Blood samples were taken for ET
      determination before and after the test. After 1 week, the test was repeated. In
      the 2 days before either the first or the second test, each volunteer randomly
      received carvedilol (C) (25 mg), an alpha 1-adrenoceptor and beta-adrenoceptor
      blocker. There was no significant difference in ET concentrations after exercise
      with or without C administration (1.24 +/- 0.66, 1.42 +/- 0.83, 1.66 +/- 1.15,
      1.61 +/- 0.87 pg/mL), showing that prolonged aerobic exercise does not affect
      plasma ET levels. Moreover, in our healthy young volunteers, blockade of alpha-
      and beta-adrenoceptors had no effect on ET levels at rest and after exercise.

PMID- 8862230
TI  - Diurnal blood pressure variation in kidney-pancreas transplant recipients.
AB  - Blood pressure normally follows a characteristic pattern throughout the 24 h
      cycle with daytime pressures higher than nighttime pressures. Patients lacking a
      nocturnal decrease in pressure have a higher incidence of end organ damage. This
      investigation was designed to characterize the diurnal pattern of blood pressure
      and to evaluate blood pressure load in patients who have received a combined
      kidney-pancreas (KP) transplant. Ten patients (mean 10 months posttransplant)
      underwent 48 h of noninvasive ambulatory blood pressure monitoring using a
      commercially available device (SpaceLabs 90202 or 90207). Blood pressure was
      measured every 15 min from 6 AM to 9 PM and every 30 min from 9 PM to 6 AM.
      Ambulatory monitoring revealed a markedly increased nocturnal blood pressure (up
      to 25% greater than daytime pressures). These patients were found to have a
      higher nocturnal blood pressure load than during the day. No relationship was
      demonstrated between diurnal blood pressure variation and immunosuppression
      regimen, elapsed time after transplantation, or antihypertensive treatment. These
      results indicate that close attention must be given to the nocturnal blood
      pressure of KP recipients and suggest that standard antihypertensive medication
      regimens do not adequately treat the nocturnal hypertension in these patients.
      This may predispose these patients to further cardiovascular or cerebrovascular
      complications.

PMID- 8862231
TI  - Regression of left ventricular hypertrophy in patients with essential
      hypertension. Results of 6 month treatment with indapamide.
AB  - Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular
      morbidity in hypertensive patients. The effects of diuretics on LVH have raised
      controversies, but recent studies suggest that diuretics are able to reduce LVH
      in hypertensive patients, mainly through a reduction in ventricular diameter. The
      present multicenter open study was designed to test the effects of indapamide, a
      widely used nonthiazide diuretic, on LVH in patients with essential hypertension.
      Patients had to have mild-to-moderate essential hypertension (supine diastolic
      blood pressure [sDBP] 95 to 115 mm Hg) with echocardiographic evidence of LVH
      (left ventricular mass index [LVMI] > 130 g/m2 for men and > 110 g/m2 for women).
      After a 2 week placebo run-in period, eligible patients underwent a 6 month
      treatment with 2.5 mg indapamide daily. All echograms were performed by the same
      investigator before and after 6 months of indapamide. Clinical and biological
      acceptability and quality of life (visual analog scale) were also studied. One
      hundred and thirty patients were included in the study and 112 completed the
      trial. Indapamide induced a significant reduction i systolic and diastolic blood
      pressures. Indapamide induced a marked reduction in posterior wall thickness
      (from 12.1 +/- 2.0 to 11.2 +/- 1.6 mm) and in interventricular wall thickness
      (from 12.7 +/- 1.7 to 11.8 +/- 1.9 mm; each P < .001) and a slight decrease in
      left ventricular diameter (P = .049). This resulted in a 13% reduction in LVMI
      (from 161.9 +/- 37.9 to 140.7 +/- 33.8 g/m2, P < .001). Left ventricular
      fractional shortening remained unchanged. There was no significant relation
      between changes in LVMI and changes in systolic, diastolic, or mean blood
      pressure. No significant adverse clinical or biological effects were reported
      during the study. The increased score of the visual analog scale indicated that
      overall well-being was improved (P < .001). Our study indicates that indapamide,
      in addition to blood pressure control, is able to reduce LVH. This effect was
      achieved mainly through a reduction in wall thicknesses rather than in internal
      cavity diameter.

PMID- 8862232
TI  - Modulation of G-protein expression by the angiotensin converting enzyme inhibitor
      captopril in hearts from spontaneously hypertensive rats. Relationship with
      adenylyl cyclase.
AB  - We have recently shown an enhanced expression of Gi alpha-2 and Gi alpha-3 at
      protein and mRNA levels and their relationship with adenylyl cyclase regulation
      in hearts and aorta from spontaneously hypertensive rats (SHR). The present
      studies were undertaken to examine if the antihypertensive action of captopril,
      an angiotensin I converting enzyme (ACE) inhibitor, is associated with the
      interaction and modulation of G-proteins and adenylyl cyclase activity. SHR and
      age-matched WKY were divided into two groups. One group of rats received
      captopril (10 mg/kg body weight) intravenously, whereas the other group received
      only vehicle (0.9% saline). The levels of Gi alpha-2 and Gi alpha-3 proteins were
      determined by immunoblotting technique using specific antisera against these
      proteins. The levels of Gi alpha-2 and Gi alpha-3 proteins were significantly
      enhanced in hearts from SHR as compared to WKY and captopril treatment restored
      the enhanced levels of Gi alpha-2 and Gi alpha-3 observed in SHR by about 70% to
      80% towards WKY control rats. However, captopril slightly decreased the levels of
      Gi alpha 2 and Gi alpha 3 protein in normotensive WKY. In addition, the
      diminished stimulation of adenylyl cyclase by isoproterenol, glucagon and N-ethyl
      carboxamide adenosine and enhanced inhibition by inhibitory hormones such as C
      type natriuretic peptide and angiotensin II observed in SHR was restored
      significantly by captopril treatment. These results suggest that one of the
      mechanisms by which captopril lowers the blood pressure may be due to its ability
      to modulate the levels of G-proteins and adenylyl cyclase activity.

PMID- 8862233
TI  - Active and passive component of ventricular diastole: is it possible to consider
      their interaction avoiding confusion?

PMID- 8862234
TI  - The reproducibility of Korotkoff 4 and 5.

PMID- 8862235
TI  - The Hypertension Optimal Treatment (HOT) Study in the United States.
AB  - The international Hypertension Optimal Treatment Study has yet to be completed
      but preliminary analysis of data has revealed trends that suggest that physicians
      in the United States treat hypertension much more aggressively than their foreign
      colleagues. At the onset of the study, the previously-treated US patients had
      blood pressures that were substantially lower than those of patients in other
      participating countries. However, after the washout period, the blood pressures
      of the US patients became the same as those of their foreign counterparts. This
      suggests that physicians in the United States aim for target blood pressures that
      are lower than those generally achieved in other countries. After participants of
      the HOT study were treated for 6 months, the blood pressure levels achieved in US
      patients were lower than those achieved in their foreign counterparts.
      Furthermore, US physicians moved their patients more quickly up the step care
      protocol, suggesting that they were much more aggressive in adding new drugs to
      treatment regimen than were physicians from other participating countries. These
      findings strongly suggest that United States physicians treat hypertension much
      more aggressively, and the fact that mortality trends in US hypertensive patients
      have decreased over the past decade lends further support for this consensus.

PMID- 8862236
TI  - Major antihypertensive intervention trials conducted outside the United States.
AB  - Five antihypertensive trials launched outside of the United States have been
      designed to address one of two vital issues. The first is whether or not there is
      an optimal level of blood pressure that clinicians should aim for to minimize the
      risk of cardiovascular disease. This has been addressed by the Swedish Behandla
      Blodtryck Battre (BBB) Trial and the international Hypertension Optimal Treatment
      (HOT) Study. The BBB Trial revealed interesting trends, but no definitive
      conclusions. The ongoing HOT Study will have to be completed before this
      particular issue can be adequately addressed. However, preliminary analysis of a
      subgroup study has revealed that the HOT treatment regimens are as effective in
      the elderly as in younger patients. The second important issue, which is the
      question of whether traditional antihypertensive agents are more effective than
      the newer agents in reducing cardiovascular risk, is the current focus of three
      ongoing studies. Investigators in the Captopril Prevention Project (CAPPP) are
      comparing captopril to beta-blocker and diuretic regimens. The purpose of the
      Nordic Diltiazem Study (NORDIL) is to determine if diltiazem is more effective
      than conventional therapy in reducing cardiovascular risk. The Swedish Trial in
      Old Patients with Hypertension-2 (STOP-Hypertension-2) has been designed to
      compare therapy with beta-blockers and diuretics to therapy with calcium
      antagonists and angiotension converting enzyme inhibitors. All ongoing trials
      should be completed in the next few years and are expected to yield valuable
      information that will improve current strategies for the treatment of
      hypertension.

PMID- 8862237
TI  - Body weight and blood pressure. Effects of weight reduction on hypertension.
AB  - A substudy of the Hypertension Optimal Treatment study, conducted in the Jackson
      Mississippi Center, set out to determine the link between obesity and
      hypertension and to determine the effects of weight loss in hypertensive
      individuals. An analysis of the relationship between body mass index and
      diastolic blood pressure for another study showed that increasing body mass
      indices were associated with increases in blood pressure. This indicates that not
      only is there a strong relationship between obesity and hypertension, but that
      there is also a close association between the continuous variables of body mass
      index and blood pressure. The purpose of the present study was to determine the
      effectiveness of a weight loss regimen in reducing the amount of medication
      required to achieve the target blood pressure in 228 patients at the Jackson
      center. Subjects were randomized to a dietary intervention group or to a control
      group. Preliminary 3 month observational data showed that subjects who lost the
      appropriate amount of weight were three times more likely to achieve their target
      blood pressure at 3 months. These observations suggest that weight reduction
      regimens can reduce elevated blood pressure and can probably promote further
      blood pressure reductions when combined with drug therapy in the treatment of
      hypertension.

PMID- 8862239
TI  - The effect of blood pressure reduction on end stage renal disease.
AB  - In the past 20 years, clinicians have clearly demonstrated that antihypertensive
      therapy is very effective in reducing the incidence of myocardial infarction and
      stroke. However, little is known about the effects of blood pressure reduction on
      end stage renal disease (ESRD). Data from major clinical studies has clearly
      shown that patients with hypertension have an increased risk of developing ESRD.
      Black men and women with hypertension are at the greatest risk; however, the
      incidence of ESRD is increasing in all racial groups. Because patients with
      hypertensive ESRD often require dialysis, the cost of treating this increasing
      common disorder has the potential to deplete the Medicare system. The primary
      effect of blood pressure reduction in patients with ESRD has not been adequately
      addressed in any trial that has been completed to date. Results from some studies
      suggest that blood pressure reduction may improve renal function and that
      angiotensin converting enzyme inhibitors and calcium channel blockers may have
      renoprotective effects. Currently in progress are two large scale clinical trials
      that may provide more information on the effects on antihypertensive therapy on
      preventing ESRD in hypertensive patients. These are the African American Study of
      Kidney Disease and Hypertension (AASK), and a substudy of the Hypertension
      Optimal Treatment (HOT) Study. Data from the HOT study is expected to be
      available 5 years prior to that of the ASK Study, which is expected to be
      completed by the Year 2002.

PMID- 8862238
TI  - Left ventricular mass and function in primary hypertension.
AB  - The Hypertension Optimal Treatment study is a prospective, randomized, clinical
      trial designed to challenge the J curve phenomenon in hypertension. A
      subpopulation of 665 patients from seven participating centers in the United
      States were enrolled to evaluate the prevalence of left ventricular mass and its
      relationship to systolic and diastolic function, as assessed by Doppler
      echocardiography, and to clinical events during the length of the study.
      Echocardiographic measurements followed stringent criteria and were rechecked in
      a core laboratory for accuracy. Baseline data revealed left ventricular
      hypertrophy in 62% of the patients. Left ventricular hypertrophy was more
      prevalent in women than in men (72% v 57%, P < .0001). The hypertrophy was
      further characterized according to left ventricular geometry and found the
      concentric pattern as the predominant form of hypertrophy (46%). Indices of left
      ventricular systolic function, including fractional shortening, cardiac index,
      and ejection fraction, were normal or above-normal. Doppler interrogation of the
      mitral inflow demonstrated left ventricular diastolic dysfunction in 81% of
      patients. The constrictive physiology (inversion of the E/A ratio) was the most
      prevalent mitral flow pattern (79%). Regression of left ventricular hypertrophy,
      modification of mass index geometry, and alterations in mitral flow
      characteristics under optimal blood pressure control will be specifically
      compared with subsequent examinations.

PMID- 8862240
TI  - Foreward: The promise and problems of capitation.

PMID- 8862241
TI  - The evolution of physician credentialing into managed care selective contracting.

PMID- 8862242
TI  - The fraud and abuse statute in an evolving health care marketplace: life in the
      health care speakeasy.

PMID- 8862243
TI  - The future role of managed care and capitation in worker's compensation.

PMID- 8862244
TI  - Provider sponsored organizations and provider service networks--rationale and
      regulation.

PMID- 8862245
TI  - Procedural protections for patients in capitated health plans.

PMID- 8862246
TI  - Capitation, advances in medical technology, and the advent of a new era in
      medical ethics.

PMID- 8862247
TI  - Insurance regulation of providers that bear risk.

PMID- 8862248
TI  - Effects of tumor necrosis factor-alpha on human trophoblast cell adhesion and
      motility.
AB  - PROBLEM: Adhesive interaction between trophoblast cells and uterine endometrial
      basement membrane is one of the critical processes in embryo implantation. This
      interaction is directly or indirectly regulated by hormones, growth factors, and
      cytokines. Since tumor necrosis factor-alpha (TNF-alpha) is synthesized by both
      decidual and trophoblast cells, we hypothesized that TNF-alpha may play a
      regulatory role in trophoblast cell invasion. To test this hypothesis, we have
      used in vitro models to determine the effect of TNF-alpha on human trophoblast
      cell adhesion and motility, two major steps in trophoblast invasion. METHODS: The
      effect of TNF-alpha on the motility of extended-lifespan first trimester
      trophoblasts (HTR) and JEG-3 choriocarcinoma cells was tested using the
      phagokinetic track motility assay. An in vitro adhesion assay was used to
      determine the effect of TNF-alpha on the adhesion of HTR and JEG-3 cells to
      laminin, a major basement membrane component. In addition, the effect of TNF
      alpha on the surface expression of the laminin receptor beta 1 integrin subunit
      was examined using flow cytometry. RESULTS: HTR or JEG-3 cells strongly adherent
      to laminin which was not significantly altered by TNF-alpha treatment. We also
      measured the effect of TNF-alpha on the surface expression of beta 1 integrin on
      HTR and JEG-3 cells; no difference was observed between control and treatment
      groups. Interestingly, the motility of both HTR and choriocarcinoma JEG-3 cells
      was significantly inhibited by TNF-alpha. CONCLUSIONS: The role of TNF-alpha in
      human embryo implantation is currently unknown. Our data demonstrate that TNF
      alpha does alter trophoblast cell adhesion to laminin, but significantly inhibits
      trophoblast cell motility in vitro, suggesting that TNF-alpha may play a
      regulatory role in trophoblast cell invasion.

PMID- 8862249
TI  - Matrix metalloproteinase expression during mouse peri-implantation development.
AB  - PROBLEM: The purpose of this study was to define the temporal expression and to
      quantitate the mRNA levels of collagenase, 72 kDa, 92 kDa, and membrane-type
      matrix metalloproteinase during the peri-implantation period of pregnancy in the
      mouse uterus. Embryonic expression of 72 kDa and 92 kDa matrix
      metalloproteinases, as well as interleukin 1 alpha, was also investigated.
      METHODS: Uterine matrix metalloproteinases were detected using gelatin substrate
      gel electrophoresis (zymography) and reverse-transcription polymerase chain
      reaction methodology was used to detect and quantitate different mRNA species in
      the mouse uterus and blastocyst. RESULTS: Collagenase, 72 kDa, and 92 kDa matrix
      metalloproteinases are developmentally regulated during the peri-implantation
      period of pregnancy, but membrane-type matrix metalloproteinase appears to be
      expressed constitutively. Matrix metalloproteinase mRNA levels have been
      quantitated and confirm the observed developmental expression patterns. Prominent
      expression of bot 92 kDa matrix metalloproteinase and interleukin 1 alpha was
      observed in blastocysts during outgrowth while weak expression of the 72 kDa
      matrix metalloproteinase was detected. CONCLUSIONS: The date provide evidence of
      matrix metalloproteinase expression in vivo and substantiate their potential role
      in tissue remodeling prior to and during blastocyst implantation. Expression of
      interleukin 1 alpha, 92 kDa, and 72 kDa matrix metalloproteinases suggests that
      these proteins are important for trophoblast invasion associated with
      implantation of the early embryo.

PMID- 8862250
TI  - Antiphospholipid antibodies in patients with preeclampsia.
AB  - PROBLEM: To determine the incidence of anticardiolipin and antiphosphatidylserine
      antibodies in women with preeclampsia. METHODS: Sera from 100 women with
      preeclampsia and 100 normotensive pregnant women in the third trimester were
      assayed for anticardiolipin and antiphosphatidylserine antibodies. RESULTS:
      Antiphosphatidylserine antibodies were positive for IgM in 1 patient (1%) and for
      IgG in 4 patients (4%). IgM antibodies to cardiolipin were positive in two
      patients (2%) while IgG antibodies to cardiolipin were positive in nine patients
      (9%). Only 3% of the control women were positive for antiphospholipid antibodies.
      None of the patients or controls had positive levels of IgA anticardiolipin or
      antiphosphatidylserine antibodies. CONCLUSIONS: Elevated levels of IgG or IgM
      antibodies to cardiolipin and phosphatidylserine were detected in 11/100 (11%) of
      women diagnosed with preeclampsia in the third trimester compared to only 3/100
      (3%) positive in controls (P < or = 0.05). These findings suggest that
      antiphospholipid antibodies may play a pathogenic role in some women with
      preeclampsia.

PMID- 8862251
TI  - Comparison of immunosuppressive properties of hydatidiform mole decidua and
      trophoblast extracts.
AB  - PROBLEMS: The immunologic privilege afforded the fetus relies upon
      immunoregulation within the maternal-fetal interface. Trophoblast and decidua
      derived immunoregulatory factors enforce this privilege by locally suppressing
      maternal responses to trophoblast antigens. The relative contribution of
      trophoblast or decidua immunosuppressive factors to pregnancy immunotolerance are
      not well characterized. The purpose of this study was to compare the suppressive
      effects of hydatidiform mole trophoblast and decidua extracts on interleukin-2
      dependent proliferation. METHOD: Tissue extracts were prepared from hydatidiform
      mole trophoblast and decidua following uterine evacuation. Samples were submitted
      to interleukin-2-dependent and -independent cell proliferation assays. RESULTS:
      Hydatidiform mole trophoblast extract significantly (P < 0.05) suppressed
      interleukin-2-dependent proliferation but did not affect interleukin-2-dependent
      cell proliferation. In contrast, molar decidua extract suppressed both cell
      lines. CONCLUSIONS: Human hydatidiform mole trophoblast contains factor(s) that
      specifically abrogate interleukin-2-dependent clonal expansion of murine
      cytotoxic T-cells. In contrast, extracts of molar decidua suppressed both
      interleukin-2-dependent and -independent responses. This indicates that the
      trophoblast antagonizes critical interleukin-2-mediated immunologic responses,
      but that the decidua uses nonspecific antiproliferative mechanisms for
      immunoregulation.

PMID- 8862252
TI  - Quantitative assessment of cytokines (GRO alpha and IL-10) in human seminal
      plasma during genitourinary inflammation.
AB  - PROBLEM: Mechanisms involved in infertility due to genitourinary (GU)
      inflammation are unknown. The production of pro-inflammatory (GRO alpha) and anti
      inflammatory (IL-10) cytokines in seminal plasma is monitored in this study.
      METHOD: GRO alpha, IL-10, and granulocyte elastase were evaluated in semen from
      I) normal, II) infertile patients, and III) infertile patients with
      leukocytospermia. RESULTS: GRO alpha in infertile patients with GU inflammation
      was 1.5-fold higher compared to group II and 2.5-fold higher compared to group I
      patients. The IL-10 was higher in group III than the other two groups. A positive
      correlation was observed between granulocyte elastase and GRO alpha in all
      groups. Group III patients exhibited poor sperm parameters. CONCLUSIONS: A shift
      towards increased production of pro-inflammatory chemokine GRO alpha may have a
      potential role in male infertility associated with GU inflammation.

PMID- 8862253
TI  - Effects of sperm immobilizing antibodies on pregnancy outcome in infertile women
      treated with IVF-ET.
AB  - PROBLEM: Since it was found that anti-sperm antibodies could impair in vitro
      development of fertilized eggs in the presence of complement in rats, the effects
      of sperm immobilizing antibodies on human pregnancy were examined in infertile
      women treated with IVF-ET. METHODS: The pregnancy outcomes of 143 ET cycles in 58
      infertile women with sperm immobilizing antibodies and 363 ET cycles in patients
      with tubal infertility as control were compared. Diagnosis of chemical pregnancy
      was done when the urinary hCG level had risen over 50 IU/L but a gestational sac
      could not be demonstrated later. Antibody titers of sperm immobilizing antibodies
      (SI50 units) were measured by a quantitative sperm immobilization test. RESULTS:
      33 (23.1%) of 143 cycles in the patients with sperm immobilizing antibodies and
      56 (15.4%) of 363 cycles in the control patients were diagnosed as pregnancy. The
      pregnancy rates were significantly higher in the former than in the latter (P <
      0.05). In the patients with sperm immobilizing antibodies, 12 (36.4%) were
      chemical pregnancies, 5 (15.2%) were clinical abortions, and 16 (48.5%) had
      deliveries. In the control group, 18 (32.1%) were chemical pregnancies, 10
      (17.9%) were clinical abortions including ectopic pregnancies and 28 (50.0%) had
      deliveries. There was no significant differences in each category. When the SI50
      titers at the time of conception were considered, chemical pregnancy rates were
      22.2% (4/18) in patients with SI50 titers below 10 units, but those in patients
      with SI50 titers above 10 were 50.0% (5/10) and above 100 were 60.0% (3/5),
      respectively, (P > 0.05). In four of five patients who had both chemical and
      clinical pregnancies, the SI50 titers at the time of conception were higher in
      the chemical pregnancy cycles than in the clinical pregnancy cycles. CONCLUSIONS:
      Though the pregnancy rates were significantly higher in the patients with sperm
      immobilizing antibodies as compared to those with tubal infertility, chemical
      pregnancy rates were also higher in the patients with higher sperm immobilizing
      antibody titers. These results suggest that sperm immobilizing antibodies may
      cause the damage of early development of human embryos in vivo in the small
      number of patients with a high titer of the antibodies.

PMID- 8862254
TI  - Globulin-enriched protein supplements shorten the pre-compaction mitotic interval
      and promote hatching of murine embryos.
AB  - PROBLEM: To determine whether Synthetic Serum Substitute (SSS), which contains
      human globulins in addition to Human Serum Albumin (HSA), is superior to HSA
      alone as a protein supplement for embryo culture. METHOD: Development of mouse
      zygotes to eight-cell/compacting morulae and to hatching/hatched blastocysts was
      assessed in Human Tubal Fluid (HTF) medium containing either SSS of HSA. RESULTS:
      Although there was no difference in the overall blastocyst rate at 120 h in
      HTF+SSS versus HTF+HSA, significantly more embryos at 54 h were at the eight
      cell/compacting morula stage in HTF+SSS. At 120 h, there were more
      hatching/hatched blastocysts in HTF+SSS, and hatching correlated with SSS
      concentration. Addition of isolated globulins to HSA significantly stimulated the
      number of hatching/hatched blastocysts. Hatching could be "rescued" by transfer
      of embryos grown in HTF+HSA to globulin-containing media and prevented by removal
      of globulins as late as the compacted morula stage (54 h). CONCLUSIONS: SSS is
      superior to HSA alone for embryo culture. The stimulatory effects on mitosis and
      hatching may be mediated directly by globulins or by other components in the
      globulin-enriched fraction.

PMID- 8862255
TI  - Susceptibility to murine experimental autoimmune oophoritis is associated with
      genes outside the major histocompatibility complex (MHC).
AB  - PROBLEM: Neonatal thymectomy induces experimental autoimmune oophoritis in
      certain strains of mice, and this serves as a model for human autoimmune
      oophoritis. Because strong MHC associations have been noted in human autoimmune
      conditions, we investigated the role of MHC in determining susceptibility to
      murine experimental autoimmune oophoritis. Strain A mice are highly susceptible
      to post-thymectomy autoimmunity, whereas strain B10 mice are relatively
      resistant. The availability of congenic strains of mice makes it possible to
      separate the effects of genetic background and specific H-2 haplotype METHODS: We
      neonatally thymectomized A and B10 background female mice, and their H-2 congenic
      counterparts, and then evaluated the resulting ovarian disease at age 6 weeks.
      RESULTS: A. By mice, which have the A background and the H-2b haplotype,
      developed severe disease equivalent to strain A mice. Similarly, B10.A mice,
      which have the B background and the H-2a haplotype, failed to develop disease.
      Thus, H-2a haplotype did not convey disease susceptibility. CONCLUSIONS: Our
      findings suggest that immune-regulatory regions outside the H-2 locus play an
      important role in determining susceptibility to murine post-thymectomy autoimmune
      oophoritis. This is in accord with our previous findings in women that showed no
      association between MHC and premature ovarian failure. Thus, in this respect this
      model is similar to human autoimmune ovarian failure. This suggests that the non
      MHC genes conveying susceptibility to autoimmune oophoritis in mice might
      represent similar predisposing genes for premature ovarian failure in women.

PMID- 8862256
TI  - Production of embryotoxic IgG antibodies during IFN-gamma treatment of pregnant
      mice.
AB  - PROBLEM: Administration of IFN-gamma during pregnancy in mice is deleterious not
      only to fetal survival but also to maternal physiology. Thus, injection of
      recombinant IFN-gamma from days 6-11 of gestation results in significant increase
      of fetal abortion, decrease of fetal weight accompanied by morphological defects
      of the embryo, and induction of class II MHC antigens on the spongiotrophoblast
      zone of the placenta. At the maternal level, this treatment causes splenomegaly,
      decrease of hematocrit levels, and increase of IgG production. In an attempt to
      dissect out the different phenomena observed, we examined the properties of
      polyclonal IgG antibodies contained in the animals' serum as to their ability to
      recognize antigenic determinants on IFN-gamma-induced placentae and isolated
      trophoblasts. METHOD: Serum from IFN-gamma-treated pregnant mice was tested in
      vitro for its ability to recognize specific structures on primary trophoblasts
      and placental sections induced by IFN-gamma. In vivo this serum was injected in
      pregnant mice, and the outcome of pregnancy was evaluated. Monoclonal antibodies,
      resulting from the fusion of spleen cells from IFN-gamma-treated pregnant mice to
      a myeloma cell line, were used to certify the IgG-dependent embryotoxic effects
      observed with the polyclonal serum. RESULTS: It was demonstrated that both the
      polyclonal serum and the monoclonal antibodies recognize antigenic determinants
      only on the IFN-gamma-induced trophoblasts, placentae, and embryos, reduce fetal
      size, and cause splenomegaly in the mother, but do not affect the percentage of
      abortions as compared to controls. CONCLUSIONS: IFN-gamma-induces specific
      protein(s) on trophoblasts, which are responsible for embryotoxic antibody
      production in the mother. Since human abortion has been correlated with the
      production of embryotoxic IgG antibodies, this animal model may prove to be a
      useful tool in the analysis of events leading to pregnancy loss.

PMID- 8862257
TI  - Human sperm coating antigen from seminal plasma origin.
AB  - Sperm surface glycoproteins may be involved in sperm-zona pellucida recognition.
      Some of these coating proteins are of seminal plasma origin and their expression
      may change in the process of capacitation and acrosome reaction. Sperm specific
      monoclonal antibodies (mAb) define the presence and role of sperm membrane
      associated proteins. We have isolated a monoclonal antibody (SEM-12) specific for
      human sperm that shows, by indirect immunofluorescence, a discontinuous
      distribution of the antigen on the head and tail surfaces of non capacitated
      sperm. This antigen is also present in human seminal plasma as detected by ELISA.
      The antigen is detectable in sperm of goat, ram, and mouse. Two proteins in the
      range of 80-84 kDa have been isolated by affinity chromatography with SEM-12 mAb.
      The same result is obtained by immunoprecipitation. This antibody inhibits sperm
      motility and acrosome reaction (spontaneous and A23187 ionophore induced.

PMID- 8862258
TI  - Primary dapsone resistance in Cebu, The Philippines; cause for concern.
AB  - At a time when primary dapsone resistance was prevalent in many leprosy endemic
      areas, Cebu in The Philippines reported only 3.6% in the period 1975-1978 and
      later 8.1% in the period 1979-1982. In our current study of patients in the
      period 1988-1992, the number increased dramatically to 52.7%. In addition, 7.9%
      of the isolates are highly resistant to dapsone, a level of resistance not seen
      in earlier studies. This finding could have severe ramifications to the World
      Health Organization's multidrug therapy (WHO-MDT) mode of treatment, where
      dapsone is one of the principal drugs. Moreover, the increase in primary dapsone
      resistance may be a contributing factor in the recent finding that there has been
      no decline in the number of new cases found in Cebu, even after the
      implementation of WHO-MDT in 1985. There is a need for new drugs that could be
      included in the multidrug treatment for multibacillary and paucibacillary
      leprosy.

PMID- 8862259
TI  - Restoration of proliferative response to M. leprae antigens in lepromatous T
      cells against candidate antileprosy vaccines.
AB  - Several studies conducted in the last decade suggest that Mycobacterium
      lepraereactive T cells exist in lepromatous patients, but their number may be too
      few to yield a detectable response in cell-mediated immunity (CMI) assays.
      Immunizations with candidate antileprosy vaccines and stimulation of T cells with
      M. leprae + interleukin-2 restore the M. leprae-induced CMI response in
      lepromatous leprosy patients. These immunizations and stimulation may enrich the
      pre-existing M. leprae-responsive T cells in lepromatous patients and, thereby,
      induce a detectable CMI response to M. leprae antigens upon repeat testing. To
      verify this proposition, we carried out a study in a group of 10 lepromatous
      leprosy patients. Peripheral blood mononuclear cells (PBMC) obtained from these
      patients were anergic to M. leprae antigens in proliferative assays, but they
      responded to the antigens of candidate antileprosy vaccines, i.e., M. bovis BCG,
      M. bovis BCG + M. leprae, and Mycobacterium w. The enrichment of M. leprae
      responsive T cells was performed by establishing T-cell lines from the PBMC after
      in vitro stimulation with M. leprae, M. bovis BCG, M. bovis BCG + M. leprae, and
      Mycobacterium w. When tested for their proliferative responses, 1/10, 3/10, 6/10
      and 2/10 T-cell lines established against M. leprae, M. bovis BCG, M. bovis BCG +
      M. leprae, and Mycobacterium w, respectively, responded to M. leprae. These
      results suggest that enrichment of pre-existing M. leprae-responsive T cells may
      contribute to the restoration of the T-cell response to M. leprae in some
      lepromatous patients. Four of the 10 M. leprae-induced T-cell lines proliferated
      in response to the 65 kDa, 36 kDa, 28 kDa, and 12 kDa recombinant antigens of M.
      leprae, suggesting that the nonresponsiveness of T cells in some lepromatous
      patients may be overcome by using recombinant antigens of M. leprae.

PMID- 8862261
TI  - Microbial colonizers in leprosy skin ulcers and intensity of inflammation.
AB  - The microflora of 55 patients with leprosy skin ulcers was studied and related to
      a weighted inflammatory score (IS). The control group consisted of 18 ulcers with
      different underlying pathology. Leprosy ulcers were characterized by the
      exclusive presence of two types of branching gram-positive rods; a particular
      interesting proposal is that Mycobacterium leprae share common antigens with
      these unusual "leprosy ulcer associated" organisms and group G beta-hemolytic
      streptococci. In the leprosy group, corynebacteria and branching rods accounted
      for 97% of gram-positive bacilli and Bacillus species constituted only 3%. In the
      control group, B. species formed 50% of gram-positive rods; the rest were
      corynebacteria (p = 0.03). In the leprosy group, one third of the gram-positive
      bacteria were branching rods; none of them was acid fast. Ten of them were
      identified as Arcanobacterium haemolyticum, and the remaining 7 could not be
      identified. The IS of leprosy patients was lower than in the control group. The
      presence of more than two species of facultative or aerobic gram-negative rods or
      single species of pyogenic gram-positive cocci correlated with a high IS. The
      presence of two or more different pyogenic cocci resulted in a lower IS. Further
      studies into the nature of leprosyunique organisms as well as the inflammation
      inhibition factors in mixed infections are warranted. It is recommended that
      management of ulcers should consist of the application of local disinfection and
      early treatment of episodes of inflammation with a combination of fluoroquinolone
      and penicillin.

PMID- 8862260
TI  - Effect of rhuIFN-gamma treatment in multibacillary leprosy patients.
AB  - Previous studies have shown that when multibacillary leprosy patients were
      treated with recombinant human interferon gamma (rhuIFN-gamma) for 6-10 months
      there was an accelerated reduction in the number of acid-fast bacilli in the skin
      at the site of injection as well as an accelerated bacillary reduction at distal
      sites. However, this favorable out-come of IFN-gamma treatment was associated
      with the development of erythema nodosum leprosum (ENL). The present study was
      undertaken to investigate whether rhuIFN-gamma-induced bacillary clearance could
      be disassociated from the induction of ENL. rhuIFN-gamma was administered
      together with thalidomide and conventional multidrug chemotherapy to newly
      diagnosed leprosy patients. During treatment with this combination of drugs, the
      mean reduction in bacterial load was the same as the reduction observed with
      chemotherapy alone. Moreover, the inclusion of thalidomide in the treatment
      regimen was associated with a low frequency of ENL episodes. A second group of
      leprosy patients, who had already completed 2 years of chemotherapy, were treated
      with rhuIFN-gamma only. In those patients who were skin bacilli negative, ENL did
      not occur during rhuIFN-gamma treatment. In contrast, in bacilli-positive
      patients the frequency of ENL during rhuIFN-gamma treatment was higher, as was
      the occurrence of local erythema and induration. However, rhuIFN-gamma treatment
      without concomitant chemotherapy did not result in a reduction in the bacterial
      load in the skin of bacilli-positive patients. These findings, taken together,
      indicate that rhuIFN-gamma does not, by itself, accelerate bacterial clearance,
      but requires concomitant chemotherapy to achieve the accelerated reduction in
      bacillary load. Thalidomide reduces the frequency of IFN-gamma-induced ENL, but
      also eliminates the IFN-gamma-induced bacillary clearance.

PMID- 8862262
TI  - Comparative trial of steroids and surgical intervention in the management of
      ulnar neuritis.
AB  - Fifty-seven ulnar nerves in 39 patients with early neuritis were studied to
      assess the benefits offered by medial epicondylectomy and external decompression
      in addition to steroid therapy. The patients were randomly allocated to the
      surgical or medical group. In those cases where there was bilateral involvement,
      surgery was carried out on only one side. All cases were assessed prior to
      treatment and after the first and second years following treatment. The
      improvement in motor and sensory functions attained at the end of the first year
      was sustained into the second year. The improvement sustained in both groups was
      similar even in the second year, and medial epicondylectomy with external
      decompression seems to have no added benefit as compared to steroid therapy alone
      in the early treatment of ulnar neuritis. Early diagnosis and treatment,
      especially in borderline lepromatous cases, seem to offer some hope of nerve
      function recovery.

PMID- 8862263
TI  - Intra- and inter-tester reliability of sensibility testing in leprosy.
AB  - We conducted an intra- and inter-tester agreement study of three sensory
      screening tests used in nerve function assessment of leprosy patients: the Semmes
      Weinstein monofilament (SWM) test, moving 2-point discrimination (M2PD), and the
      pin prick test. The weighted kappa (Kw) statistic was used as the reliability
      coefficient. The SWM had intra-observer Kws ranging from 0.83 to 0.92 and inter
      observer Kws ranging from 0.76 to 0.89. The M2PD had intra- and inter-tester Kws
      ranging from 0.75 to 0.82 and 0.54 to 0.82, respectively. Inter-tester agreement
      for the pin prick test ranged from 0.45 to 0.85. There was evidence that the main
      source of variability between testers was testing skill and experience. Among the
      experienced physiotechnicians there was no significant difference between intra-
      and inter-tester reliability. We conclude that reliability of the SWM test was
      very good, closely followed by the M2PD test. Reliability of the pin prick test
      was less good than that of the SWM and M2PD, making it less suitable for serial
      testing.

PMID- 8862264
TI  - Recognition of lipid antigens by sera of mice infected with Mycobacterium
      lepraemurium.
AB  - Lipids extracted from mouse tissues infected with Mycobacterium lepraemurium
      (MLM) were analyzed by thin-layer chromatography. Although the extracted lipids
      were heterogeneous in polarity, the lipids of intermediate polarity were the ones
      that predominated. All of the lipids of intermediate polarity were glycosylated
      species. There were also lipids of low and high polarity, the latter being
      glycolipids. Compared to lipids extracted from normal tissue (mostly to lipids of
      high and low polarity), all of the additional lipids extracted from the infected
      tissue corresponded to lipids present in the purified bacteria. Enzyme-linked
      immunoassays (ELISAs) were then performed with the whole lipids extracted from
      purified bacilli, the lipids of high, intermediate and low polarity, and the sera
      from 20 normal and 20 MLM-infected mice. Lipids of intermediate polarity were
      specifically recognized by MLM-infected mice. Neither sera (diluted 1:500) from
      normal mice nor infected mice reacted with the lipids of high or low polarity,
      but a higher concentration (sera diluted 1:100) of some sera from mice in both
      groups reacted significantly with these lipids. In the ELISAs the whole-lipid
      extract and the lipids of intermediate polarity were similarly recognized by the
      sera of the infected mice. Thus, as observed in human leprosy, the mycobacterial
      disease in the mouse (murine leprosy) is also accompanied by the development of
      antibodies to the glycolipids of the infecting microorganism.

PMID- 8862266
TI  - Multibacillary nerve histology in clinically diagnosed borderline tuberculoid
      leprosy patients.
AB  - The classification of leprosy into multibacillary (MB) and paucibacillary (PB)
      patients in almost all clinics is entirely dependent on clinical examination. In
      a study of 21 patients clinically classified as borderline tuberculoid (BT) and,
      therefore, belonging to the PB group, skin smears and skin and nerve biopsies
      were examined. Four patients did not have any histopathological evidence of
      leprosy. Skin smears showed that 1 patient was positive for acid-fast bacilli
      (AFB), 2 skin biopsies belonged to the borderline lepromatous (BL) category and
      showed AFB in their lesions, and AFB were present in 10 nerve biopsies classified
      as BL. It is possible that reported relapses among PB patients may be in those
      patients with demonstrable AFB in the lesions, including nerves. A careful follow
      up study of this particular group of patients after PB multidrug therapy is
      suggested to resolve this question.

PMID- 8862267
TI  - 70th anniversary of the Rubino reaction.

PMID- 8862265
TI  - Silent iritis in treated bacillary negative leprosy.
AB  - Iridectomy specimens from 59 leprosy patients who had adequate medical records of
      whom 33 belong to the lepromatous (LL) leprosy variety and 16 normal controls
      were studied histopathologically. All patients were bacteriologically negative
      and had received dapsone followed by multidrug therapy (MDT), or MDT only, or
      only dapsone for varying periods. It was found that leprosy, particularly
      lepromatous disease, did not significantly decrease the age of formation of
      cataract. Of the 33 LL patients studied 60.6% had silent iritis. The duration of
      treatment had no obvious influence on the persistence of iritis. Treatment with
      only 2 years of MDT for LL patients did not significantly increase the prevalence
      of persistent silent iritis compared to those who received other types of
      antileprosy therapy for long periods. It is pointed out that chronic iritis is a
      serious complication that continues even after the patient is declared clinically
      and bacteriologically cured, especially in patients who had a history of chronic
      iritis clinically.

PMID- 8862268
TI  - Antiphospholipid antibodies thrombotic syndrome misdiagnosed as Lucio's
      phenomenon.

PMID- 8862269
TI  - Penile lesion in Hansen's disease.

PMID- 8862270
TI  - Investigation of anti-Mycobacterium leprae antibodies in leprosy patients' sera
      by an A60 antigen immunoassay.

PMID- 8862271
TI  - Antibodies to phenolic glycolipid-I and sulfatide-I in leprosy and tuberculosis.

PMID- 8862272
TI  - NADPH-oxidase activity triggered by endocytosis of yeast in circulating
      phagocytes of nine-banded armadillos (Dasypus novemcinctus)

PMID- 8862273
TI  - Effect of Mycobacterium leprae on peripheral nerve protein phosphorylation; a
      preliminary study.

PMID- 8862274
TI  - Electron-microscopic study of negative Mitsuda reaction in nine-banded armadillos
      and lessons to be learned.

PMID- 8862275
TI  - Myopathy and spontaneous Pasteurella pneumotropica-induced abscess formation in
      an HIV-1 transgenic mouse model.
AB  - In an effort to augment human immunodeficiency virus type 1 (HIV-1) gene
      expression in transgenic mice, an infectious proviral DNA clone was modified by
      deleting the two NF kappa B binding sites and some adjacent upstream LTR
      sequences and replacing them with the core enhancer of Moloney murine leukemia
      virus (MLV). Two independent lines of MLV/HIV transgenic mice were established
      that expressed HIV-1-specific RNA in lymphoid tissue, striated skeletal muscle,
      and the eye lens. Heterozygous animals from each transgenic line spontaneously
      developed an inflammatory disease of the eye associated with the production of
      copious amounts of purulent lacrimal secretions beginning at 2 weeks of age.
      Periorbital abscess formation became grossly apparent by 2 months of age and
      Pasteurella pneumotropica was cultured from the harderian glands and conjunctival
      surfaces of many of the MLV/HIV animals but not their nontransgenic, cohabiting
      littermates. This gram-negative commensal bacterium has been previously
      associated with a similar disease phenotype in immunocompromised (e.g., nude
      mice) rodent colonies. MLV/HIV mice developed normally until 15 weeks of age,
      when weight loss and wasting occurred, culminating in premature death (as earlier
      as 6 months of age). The cachexia was associated with an initially focal and
      subsequently progressive myopathy, coinciding with age-related increases of HIV
      gene expression in muscle.

PMID- 8862276
TI  - Development of T-cell lines expressing functional HIV-1 envelope glycoproteins
      for evaluation of immune responses in HIV-infected individuals.
AB  - The human T-lymphoid cell line, CEM, was transfected with gp 160 cDNA of human
      immunodeficiency virus type 1 (HIV-1)pm213. Three clones expressing the envelope
      glycoproteins (env), designated CEM-213env1, -env4, and -env7, were isolated.
      These clones expressed high levels of surface gp41 and gp120, as demonstrated by
      flow cytometry with anti-HIV env monoclonal antibodies. Processing and function
      of env was shown by induction of syncytia with CD4-expressing HeLa cells and by
      immunoblot analysis. The env expression resulted in specific down-regulation of
      surface CD4 levels, supporting the role of HIV env in CD4 modulation.
      Furthermore, serum samples from nine of nine HIV-1-infected individuals bound
      specifically to the env-expressing transfectants, substantiating the presence of
      conserved antigenic determinants. These sera also mediated antibody-dependent
      cellular cytotoxicity (ADCC) of the env-expressing cell lines. The env-expressing
      cell lines provide a relevant, safe, and practical model for qualitative and
      quantitative analysis of humoral and cellular immune responses and their role in
      HIV-1 pathogenesis and therapy.

PMID- 8862277
TI  - Quantification of HIV-1 RNA in plasma: comparable results with the NASBA HIV-1
      RNA QT and the AMPLICOR HIV monitor test.
AB  - We investigated and compared the reproducibility, accuracy, detection limits, and
      dynamic ranges of two commercial kits for quantification of RNA viral load using
      a titrated virus stock (laboratory strain HIV-1 IIIB) and 107 plasma samples of
      25 HIV-1-infected patients. The high reproducibility of both methods (SD = 0.2
      0.3 log for both methods) allowed reliable detection of a 0.5 log change in RNA
      viral load. Both methods had a similar detection limit (at least 10(3) RNA
      copies/ml plasma) and a dynamic range that extended over a 5 log (AMPLICOR) or a
      6 log (NASBA) range of HIV-1 input. For HIV-1 IIIB, the viral load was compatible
      with measurements of virus-associated p24 antigen. For 21 patients (91 samples),
      the RNA viral load was similar with both methods differing by no more than 0.5
      log. For four patients, the difference in viral load between the two methods was
      > 0.5 log for all 16 samples. For three of these patients, this could be
      explained by mismatches with primers or probes in the gag sequence: there was no
      correlation to the viral subtype. The RNA viral load determination was highly
      sensitive compared with p24 antigen measurement (> 95% of patients had a
      detectable viral load vs. 40% who had a detectable p24 level), but in the p24
      positive samples the correlation between the antigen level and the RNA viral load
      was of only borderline significance. We also found that the viral RNA in whole
      blood was stable for at least 48 h during transport at room temperature. These
      observations show that both the NASBA HIV-1 RNA QT test and the AMPLICOR HIV
      monitor test are reliable parameters of the viral load, with great promise for
      their use as potential surrogate markers.

PMID- 8862278
TI  - Reverse transcriptase mutations in HIV-1-infected children treated with
      zidovudine.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutations
      were detected in DNA from peripheral blood mononuclear cells from 11 of 12 HIV-1
      infected children after 11-20 months of zidovudine monotherapy. The number of
      children with mutations detected at each codon were as follows: codon 41, 4;
      codon 67, 2; codon 70, 7; codon 215, 7; codon 219, 0. Codon 41 mutations were
      found only in the presence of a codon 215 mutation and in the absence of a codon
      70 mutation. The codon 41/215 mutant combination was associated with decline in
      weight-for-age z score during therapy, weight < 10th percentile, CD4+ cell counts
      < 3rd percentile, and immune-complex dissociated HIV-1 p24 antigen (ICD p24 Ag)
      levels > 100 pg/ml. Patients developing the codon 70 mutation tended to have body
      weight > 30th percentile, CD4+ cell counts > 25th percentile, and ICD p24 Ag <
      100 pg/ml. The codon 41 mutation was associated with clinical deterioration
      during a 6-month followup period.

PMID- 8862279
TI  - Infections associated with totally implantable venous access devices (TIVAD) in
      human immunodeficiency virus-infected patients.
AB  - We report on a retrospective study evaluating infectious morbidity associated
      with totally implantable venous access devices (TIVAD) (Port-A-Cath) in HIV
      infected patients. This study of 84 consecutive HIV-infected patients requiring
      89 TIVAD between January 1990 and October 1993 was performed in the Department of
      Infectious Diseases Hopital de l'Institut Pasteur, Paris, France. The total
      number of catheter days was 11,595. Eighteen of 89 patients with TIVAD (20%) were
      infected, causing 25 infectious events (25/89: 28%) among 17 different patients
      (17/84: 20%). The infection rate was 0.22 per 100 catheter days. Mean onset of
      infection was 82 days. Twenty microorganisms were isolated: Staphylococcus aureus
      in eight cases (40%), coagulase-negative Staphylococcus in six cases (30%),
      Streptococcus D faecalis in one case; Gram-negative bacilli were found in five
      cases (25%). All patients received an intravenous antibiotherapy combined with a
      local lock treatment in eight cases. Nine TIVAD removals were performed. One
      death was related to the TIVAD infection. No additional predisposing factor for
      infection was identified other than the implied condition of the HIV infection.
      The population and material in this study were homogeneous. The TIVAD infection
      rate was comparable to other published reports. Prospective evaluation comparing
      tunneled catheter and TIVAD in HIV-infected patients is needed.

PMID- 8862280
TI  - Human immunodeficiency virus infection in children with tuberculosis in Santo
      Domingo, Dominican Republic: prevalence, clinical findings, and response to
      antituberculosis treatment.
AB  - We studied human immunodeficiency virus (HIV)-seroprevalence among children with
      clinically diagnosed tuberculosis (TB) and compared the clinical features and
      response to short-term anti-TB therapy of children with and without HIV infection
      in Santo Domingo, Dominican Republic. Children aged 18-59 months with new-onset,
      clinically diagnosed TB were tested for HIV antibodies, their clinical features
      were recorded and their response to a standard 6-month regimen of daily isoniazid
      and rifampicin with daily streptomycin and pyrazinamide for the first 2 months
      was assessed. To increase the number of HIV-infected children with TB available
      for study, we also included children previously known to be HIV infected who
      developed new-onset TB. Eleven (5.8%) of 189 consecutively enrolled children with
      clinically diagnosed TB were HIV infected. Fifteen other children with previously
      documented HIV infection and new-onset TB were available for study, yielding 26
      HIV-positive and 178 HIV-negative children with TB. Of these 204 children with
      clinically diagnosed TB, 25 HIV-positive and 156 HIV-negative children were
      successfully followed for 6 months or until death. The proportion of HIV-positive
      children who failed treatment was 6 (29%) of 21 as compared with only 5 (3%) of
      156 HIV-negative children [relative risk = 8.9; 95% confidence interval (CI) 2.9,
      26.6; p = 0.0004]. HIV-infected children with clinically diagnosed TB are
      substantially more likely to fail standard treatment for TB than are HIV
      uninfected children. If standard treatment regimens are used in such children,
      response to treatment must be monitored very closely and appropriate changes in
      the regimen must be made expeditiously.

PMID- 8862281
TI  - Model of the impact of HIV infection on the size of future hemophilia and carrier
      birth cohorts.
AB  - The introduction of human immunodeficiency virus (HIV) infection in almost half
      of the U.S. hemophilia population during the late 1970s and early to mid-1980s
      has resulted in significant mortality and morbidity. The predict the quantitative
      impact of HIV infection through HIV-contaminated clotting factor on the size of
      future hemophilia and hemophilia carrier populations in the United States, a
      demographic model was developed for hemophilia and hemophilia carrier birth
      cohorts for the 200 years between 1980 and 2180. Mortality and fertility rates
      were estimated from databases of the Hemophilia Malignancy Study (HMS), NHLBI
      Blood Resources Studies, and Centers for Disease Control (CDC) Minimal Data Set.
      According to the model, the HIV epidemic will produce small reductions in the
      expected numbers of hemophilic (1.79%) and carrier (2.63%) births in the next 2
      centuries. More substantial reductions in the numbers of hemophilic and carrier
      births required extreme assumptions regarding the fertility of hemophilic men,
      the extent of HIV infection among hemophilic men, and the proportion of
      hemophilic births that arise from spontaneous mutation.

PMID- 8862282
TI  - Determinants of HIV seroprevalence rates among sites participating in a community
      based study of drug users.
AB  - The National Institute on Drug Abuse's National Cooperative Agreement Project is
      a nationwide study of the injection and sexual behaviors of three populations of
      out-of-treatment drug users: injecting drug users (IDUs) who did not smoke crack
      cocaine, non-injecting crack smokers, and those engaging in both types of use.
      The goal of the analyses we present was identification of subsets of behavioral
      variables that would, within each type of drug use, distinguish sites by HIV
      seroprevalence level. Among non-crack-smoking IDUs high seroprevalence rates were
      associated with race and sex, the overall frequency of injection, the frequency
      of cocaine injection, and geographic location. Among noninjecting crack smokers,
      cities were distinguished by the frequency of exchanging sex for money, the
      number of sex partners, the local seroprevalence rate among IDUs, and location.
      Among subjects engaging in both types of use, seroprevalence rates among sites
      was distinguished by the frequency of exchanging sex for drugs and location.

PMID- 8862283
TI  - Tuberculosis and HIV infection among female inmates in Sao Paulo, Brazil: a
      prospective cohort study.
AB  - Prison populations are at increased risk of both human immunodeficiency virus
      (HIV) and Mycobacterium tuberculosis infections, but among female inmates
      information on such risks remains scarce, especially in developing countries.
      Between October 1992 and November 1993, 350 women incarcerated at a prison in Sao
      Paulo, Brazil, were prospectively evaluated for HIV and M. tuberculosis infection
      and disease. Among them, 87 (25%) were HIV seropositive, and 20 (5.7%) had
      tuberculosis (TB). During the incarceration period, the purified protein
      derivative test conversion rate was 29% for HIV-positive and 32% for HIV-negative
      women. However, the incidence of TB was 9.9 per 100 person-years for HIV-positive
      and 0.7 per 100 person-years of incarceration for HIV-negative women (p <
      0.0001). A multivariate analysis indicated that HIV infection (p < 0.0001) and
      incarceration time < 12 months (p < 0.05) were each associated with TB. These
      findings indicate that new transmissions of M. tuberculosis infection are common
      among female inmates and that HIV-infected women are more likely to acquire
      active disease during the first 12 months of incarceration. Because of their role
      in childbearing and care female inmates are an important potential source of
      transmission of M. tuberculosis, and new strategies to control the spread of TB
      in prisons need to be developed.

PMID- 8862284
TI  - Role of neopterin and 7,8-dihydroneopterin in human immunodeficiency virus
      infection: marker for disease progression and pathogenic link.
AB  - Human immunodeficiency virus (HIV) infection is associated with increased
      concentrations of neopterin derivatives, released in large quantities by human
      macrophages on stimulation with interferon-gamma (INF-gamma). Neopterin
      concentrations thus inversely correlate with absolute CD4+ T-cell numbers and
      strongly predict progression of disease from latency to AIDS. Investigations of
      hydrogen peroxide-induced chemiluminescence indicated a potential role of
      neopterin and 7,8-dihydroneopterin in oxygen free radical-mediated processes.
      Indeed, 7,8-dihydroneopterin is able to enhance tumor necrosis factor alpha (TNF
      alpha)-induced apoptosis, accompanied by an increased production of reactive
      oxygen intermediates (ROIs). In line with this finding, the same combination
      appears to contribute to the upregulation of HIV replication due to activation of
      nuclear factor-kappa B (NF-kappa B), a central enhancer element of the HIV LTR
      promoter. Thus, besides the role of neopterin as sensitive indicator of disease
      activity in HIV infection, neopterin derivatives apparently are associated with
      the cascade of events that regulate the HIV production in infected individuals.

PMID- 8862285
TI  - Absence of human herpesvirus 8 DNA sequences in neoplastic Kaposi's sarcoma cell
      lines.
AB  - The recent detection of herpesvirus-like DNA sequences in Kaposi's sarcoma (KS)
      lesions has led to numerous speculations regarding the role of this new agent in
      KS pathogenesis. However, recent studies indicate a far wider distribution of
      such viral sequences, shadowing the potential etiologic role of this agent in KS.
      In this report we show that malignant KS cell lines do not harbor such viral
      sequences while B cells, CD14+ and CD34+ cells do, suggesting that if a KS
      malignancy originates from infection with HHV-8, the virus can be lost and is not
      necessary for maintenance of the neoplastic state. Alternatively, HHV-8 may be a
      "passenger" in KS.

PMID- 8862286
TI  - The new era of DEXA.

PMID- 8862287
TI  - Nuclear medicine: 100 years in the making.

PMID- 8862288
TI  - Comparison of iodine-123-epidepride and iodine-123-IBZM for dopamine D2 receptor
      imaging.
AB  - Although 123I-IBZM is widely used as a D2 receptor imaging agent, image quality
      is compromised by a relatively low target-to-nontarget ratio. Animal studies
      suggest that 123I-epidepride (Kd 0.024 nM) may be superior to 123I-IBZM, but this
      agent has not been systematically studied in humans. METHODS: We directly
      compared 123I-epidepride and 123I-IBZM in five normal volunteers (age range 30-58
      yr, mean 43 yr). Brain SPECT imaging was performed 2 hr after the 123I-IBZM
      injection (average dose 153 MBq). Iodine-123-epidepride scans were performed 1 hr
      (n = 3), 2 hr (n = 5) and 3 hr (n = 3) postinjection (average dose 149 MBq).
      RESULTS: Both radiopharmaceuticals were well tolerated. Iodine-123-epidepride
      provided excellent visualization of the striatum. Percent specific striatum
      uptake at 2 hr (71.7 +/- 4.9%) was much greater than with 123I-IBZM (32.6 +/-
      5.3%, p < 0.01). CONCLUSION: Iodine-123-epidepride is a new D2 receptor agent
      that exhibits excellent neuroimaging properties and has a much higher affinity
      for striatal uptake than 123I-IBZM.

PMID- 8862289
TI  - SPECT imaging of dopamine receptors.

PMID- 8862290
TI  - Brain SPECT with dipyridamole stress to evaluate cerebral blood flow reserve in
      carotid artery disease.
AB  - This is a preliminary study of SPECT brain scan using dipyridamole as a stress
      agent to assess cerebral blood flow reserve in six patients with severe carotid
      artery disease. METHODS: We performed SPECT scanning of the brain, with and
      without dipyridamole stress. Dipyridamole (0.57 mg/kg) was given intravenously 3
      min before infusion of 99mTc-HMPAO. Patients were studied 30 min later using a
      rotating head gamma camera. The scans were analyzed qualitatively and
      semiquantitatively. An acetazolamide stress SPECT image was also obtained in two
      patients. RESULTS: All patients had at least 80% stenosis in one internal carotid
      artery, three of them also had contralateral carotid stenosis. The dipyridamole
      SPECT showed an increased region of hypoperfusion in the hemisphere ipsilateral
      to the severe carotid disease in four patients. That suggests poor perfusion
      reserve and the potential risk of regional ischemia. In four of six patients,
      side-to-side asymmetry increased from the baseline condition after injection of
      dipyridamole. The asymmetry index increased more after dipyridamole than after
      acetazolamide injection in two patients. CONCLUSION: This study suggests that
      dipyridamole stress SPECT is useful in assessing cerebral blood flow reserve. It
      demonstrates the region of poor vascular reserve in patients with severe carotid
      artery disease. Dipyridamole SPECT scans show more extensive hypoperfusion than
      acetazolamide in the two cases.

PMID- 8862291
TI  - One-year follow-up of technetium-99m-HMPAO SPECT in mild head injury.
AB  - We evaluated the predictive capacity of 99mTc-HMPAO SPECT for clinical outcome
      during a follow-up period of 12 mo after mild head injury. METHODS: We
      prospectively evaluated 136 patients with mild head injury who underwent initial
      SPECT imaging (SPECTO) within 4 wk after the trauma. Re-evaluations were made 2.9
      3.3 mo (T3mo), 5.7-6.3 mo (T6mo) and 11.9-12.6 mo (T12mo) postinjury. All
      patients with an abnormal SPECT underwent a repeat study at the subsequent time
      of evaluation. Patients with a previously normal SPECT scan did not undergo a
      repeat study. Clinical reassessments (CLIN) were performed as long as the earlier
      study had been positive or until patients were completely asymptomatic. RESULTS:
      During all follow-up evaluations, SPECT had a high sensitivity and negative
      predictive value, increasing from 91% and 89%, respectively, at T3mo to 100% at
      T6mo and at T12mo. Clinical normalization occurred earlier than scintigraphic
      normalization. However, at 12 mo postinjury, we observed considerable improvement
      in the specificity and positive predictive value of SPECT (85% and 83%,
      respectively). The persistent lesions on the SPECT scan were related to their
      severity and to localization in the frontal cortex. CONCLUSION: A normal 99mTc
      HMPAO SPECT scan is a reliable tool in the exclusion of clinical sequelae of mild
      head injury. At 12 mo postinjury, a positive SPECT study is also a reliable
      predictor for clinical outcome.

PMID- 8862292
TI  - Reproducibility of regional brain metabolic responses to lorazepam.
AB  - Changes in regional brain glucose metabolism in response to benzodiazepine
      agonists have been used as indicators of benzodiazepine-GABA receptor function.
      The purpose of this study was to assess the reproducibility of these responses.
      METHODS: Sixteen healthy right-handed men underwent scanning with PET and
      [18F]fluorodeoxyglucose (FDG) twice: before placebo and before lorazepam (30
      micrograms/kg). The same double FDG procedure was repeated 6-8 wk later on the
      men to assess test-retest reproducibility. RESULTS: The regional absolute brain
      metabolic values obtained during the second evaluation were significantly lower
      than those obtained from the first evaluation regardless of condition (p < or =
      0.001). Lorazepam significantly and consistently decreased both whole-brain
      metabolism and the magnitude. The regional pattern of the changes were comparable
      for both studies (12.3% +/- 6.9% and 13.7% +/- 7.4%). Lorazepam effects were the
      largest in the thalamus (22.2% +/- 8.6% and 22.4% +/- 6.9%) and occipital cortex
      (19% +/- 8.9% and 21.8% +/- 8.9%). Relative metabolic measures were highly
      reproducible both for pharmacologic and replication condition. CONCLUSION: This
      study measured the test-retest reproducibility in regional brain metabolic
      responses, and although the global and regional metabolic values were
      significantly lower for the repeated evaluation, the response to lorazepam was
      highly reproducible.

PMID- 8862293
TI  - SPECT and MRI evaluations of the posterior circulation in moyamoya disease.
AB  - We evaluated the posterior circulation in patients with moyamoya disease by SPECT
      and MRI. METHODS: Six patients with idiopathic moyamoya disease were studied by
      SPECT, MRI and angiography. Patients received an injection of 555-740 MBq of
      99mTc-HMPAO, after which SPECT images were taken. The cerebral-to-cerebellar
      activity ratio in five cerebral regions was calculated to assess the regional
      cerebral blood flow (rCBF). The SPECT and MRI findings were then compared with
      angiographic. RESULTS: Of the 12 posterior cerebral arteries (PCAs) in the six
      patients studied, seven PCAs (58%) in five patients had a stenotic or occluded
      lesion. Furthermore, rCBF in all five regions significantly decreased as the
      degree of steno-occlusive lesions of the PCA progressed. No significant
      correlation, however, was found between the steno-occlusive lesions of the
      internal carotid artery bifurcation and the rCBF. The rCBF significantly
      decreased in the absence of leptomeningeal collateral vessels from the PCA to the
      anterior circulation. On the basis of the MR images, the frequency of cerebral
      infractions significantly increased in patients with steno-occulasive PCA
      lesions. CONCLUSION: The rCBF in moyamoya disease decreases proportionally with
      the degree of steno-occlusive lesions of the PCA. The steno-occlusive PCA lesions
      decrease the number of leptomeningeal collateral vessels to the anterior
      circulation, thereby causing severe cerebral ischemia that is likely to result in
      infractions.

PMID- 8862294
TI  - Myocardial perfusion scintigraphy: effect on diagnostic and clinical management
      algorithms.
AB  - Research has demonstrated that myocardial perfusion imaging increases the
      sensitivity and specificity of stress electrocardiography. However, the
      additional effect of the perfusion component of a stress study on clinical
      management algorithms remains poorly defined. METHODS: We prospectively assessed
      the decision-making process in 518 patients, from 191 clinicians, undergoing
      stress myocardial perfusion imaging in our departments. Each clinician was asked,
      by telephone interview, to define the probability of reversible myocardial
      ischemia and their management plan (i.e., no antianginal treatment, medical
      therapy or an invasive intervention) in three stages: pretest, after the stress
      data was made available and after completion of the perfusion study. RESULTS: The
      results of the stress data alone influenced the estimate of the probability of
      reversible ischemia in 149 of 518 patients, and management strategy in 50 of 518
      patients. The data from the perfusion component in isolation changed probability
      of reversible disease in 219 of 518 patients and altered clinical management in
      77 of 518 patients. Of 103 patients in whom an invasive procedure was planned
      after the stress data, the availability of the perfusion data led to deferral of
      catheterization in 48 cases (46.6%). Conversely, of the 415 patients triaged to a
      noninvasive plan after stress data, only 29 (7.0%) were changed to an invasive
      strategy. Of note, only 2.3% of women changed from a conservative strategy as a
      consequence of the perfusion data, compared to 9.1% of men. CONCLUSION: The
      perfusion component of a stress study has a significant effect on both estimation
      of clinical probability and the definition of patient management strategy.
      Myocardial perfusion imaging reduced the number of catheterizations in patients
      initially triaged to an invasive management strategy. Conversely, the effect of
      stress and perfusion data in patients triaged to conservative management on
      clinical grounds, especially women, remains less well defined.

PMID- 8862295
TI  - Early and delayed technetium-99m-tetrofosmin myocardial SPECT compared in normal
      volunteers.
AB  - This study was performed to test the feasibility of early SPECT imaging with
      99mTc-tetrofosmin with the presence of high hepatic activity. METHODS: Thirteen
      normal volunteers were injected 600-740 MBq of 99mTc-tetrofosmin at rest and were
      imaged at 10 min and 1 hr after injection. The SPECT images were reconstructed
      for 180 degrees 360 degrees data. The early and delayed SPECT and anterior planar
      projection images were analyzed. RESULTS: After excluding one subject because of
      high hepatic activity overlapping to the myocardium, 4 of 12 subjects (33%) had
      abnormal scans with reduced uptake in the inferior wall on the early 180 degrees
      SPECT image. In contrast, only one (8%) showed equivocally reduced uptake on the
      360 degrees SPECT image. In the delayed images, all subjects had a normal 180
      degrees and 360 degrees SPECT scan. Quantitative data showed reduced regional
      activities in the inferior wall on the early SPECT scan, especially in the 180
      degrees data. There were no changes in the mean anterior-to-inferior ratio in the
      anterior planar projection images over time, suggesting that the reduced activity
      in the early SPECT images reflected an artifactual effect. CONCLUSION: Our data
      indicate that it would be best to perform late imaging in patients with suspected
      coronary artery disease using 99mTc-tetrofosmin.

PMID- 8862296
TI  - Reproducibility of measurements of regional resting and hyperemic myocardial
      blood flow assessed with PET.
AB  - PET with 13N-ammonia permits the noninvasive quantification of myocardial blood
      flow (MBF) in humans. The present study was done to assess the reproducibility of
      quantitative blood flow measurements at rest and during pharmacologically induced
      hyperemia in healthy individuals. METHODS: Thirty healthy volunteers (26 men, 4
      women) were studied. Paired measurements of MBF at rest (n = 21), during
      adenosine (n = 15) and during dipyridamole (n = 7) were performed using a two
      compartment model for 13N-ammonia PET. The mean difference between baseline and
      follow-up blood flow (% difference) was calculated to assess reproducibility.
      RESULTS: No significant difference was observed between resting blood flow at
      baseline or follow-up (15.8% +/- 15.8%; p = ns). Baseline and follow-up resting
      blood flow were linearly correlated (r = 0.63, p < 0.005). Normalization of
      resting blood flow to the rate pressure product improved the reproducibility
      significantly (15.8% +/- 15.8% versus 10.1% +/- 10.5%, p < 0.05). Baseline and
      follow-up hyperemic myocardial blood flow did not differ (11.8% +/- 9.4%; p = ns)
      and were linearly correlated (r = 0.69, p < 0.0005). CONCLUSION: MBF at rest can
      be measured reproducibly with 13N-ammonia PET. The individual response to
      pharmacologic stress appears to be relatively consistent. Thus, serial blood flow
      measurements with 13N-ammonia PET can be used to quantify the effect of various
      interventions on MBF and vasodilatory reserve.

PMID- 8862298
TI  - Matched ventilation, perfusion and chest radiographic abnormalities in acute
      pulmonary embolism.
AB  - This investigation assessed the positive predictive value of matched
      ventilation/perfusion (V/Q) and chest radiographic defects (triple-matched
      defects) for the detection of acute pulmonary embolism (PE). METHODS: Data are
      from the Prospective investigation of Pulmonary Embolism Diagnosis (PIOPED). Only
      patients randomized for obligatory pulmonary angiography were included. Lungs
      were excluded if they showed any mismatched V/Q defect or any pleural effusion.
      RESULTS: Positive predictive values of triple-matched defects in the upper plus
      middle zones, 1 of 27 (4%), were less frequent than in the lower zones, 13 of 57
      (23%) (p < 0.05). Triple-matched defects that involved 25-50% of a zone showed PE
      in 12 of 38 (32%) which was a higher positive predictive value than with smaller
      or larger triple-matched defects, 2 of 46 (4%) (p < 0.001). CONCLUSION:
      Refinement of the PIOPED data by elimination of nonrandomized patients,
      elimination of lungs with mismatched perfusion defects and elimination of lungs
      with a pleural effusion indicate that triple matches with PE (radiographic
      pulmonary infarcts) are infrequent in the upper and middle lung zones. When a
      triple match with PE occurs, it is most likely to be 25-50% of a zone.

PMID- 8862297
TI  - Comparison of myocardial uptake of fluorine-18-fluorodeoxyglucose imaged with PET
      and SPECT in dyssynergic myocardium.
AB  - PET with 18F-fluorodeoxyglucose (FDG) can detect viable myocardium and predict
      functional recovery after revascularization. The use of PET for clinical routine,
      however, is limited. Recently, imaging FDG with SPECT was proposed. The aim of
      this study was to compare the diagnostic value of FDG-PET and FDG-SPECT in the
      detection of viable myocardium in segments with abnormal wall motion. METHODS:
      Twenty patients with previous myocardial infarction were studied. All underwent
      FDG-PET and FDG-SPECT during hyperinsulinemic glucose clamping. Regional
      perfusion was assessed with 13N-ammonia PET and early resting 201TI- SPECT.
      Regional wall motion was assessed with two-dimensional echocardiography. The
      agreement between FDG/13N-ammonia PET and FDG/201TISPECT to detect viability in
      dyssynergic myocardium was 76%. On a patient basis, PET and SPECT yielded
      comparable results in 17 of 20 patients. In a subgroup of patients with LVEF < or
      = 35% (n = 12), all PET and SPECT viability data were identical. CONCLUSION: This
      study shows a good correlation between the detection of viability in dyssynergic
      myocardium with FDG/13N-ammonia PET and FDG/201TI SPECT, both on a segmental and
      patient basis.

PMID- 8862299
TI  - Lag phase quantification for solid gastric emptying studies.
AB  - This study compared the different calculation methods of the solid gastric
      emptying lag phase and evaluated the effect of the temporal sampling interval on
      the calculated value using the modified power exponential (MPE) method. METHODS:
      Twenty normal control subjects and 42 patients had anterior and posterior image
      acquisition on a multihead gamma camera, one frame per minute x 90. ROIs were
      selected for the stomach, gastric antrum and small bowel. Time-activity curves
      (TACs) were generated for anterior, posterior and geometric mean data. The lag
      phase was calculated using various methods such as transition point, starting
      index, first appearance of bowel activity (FABA), MPE and antral peak filling
      time. To determine the importance of the temporal sampling rate on the
      calculation of the lag phase by the MPE, intervals between 1 and 20 min were
      analyzed. RESULTS: The transition point, starting index and FABA correlated
      extremely high (r = > or = 0.92) in normal control subjects and patients. Normal
      lag phase values were mean 22-24 +/- 10 min for transition point, starting index
      and FABA compared with 47 +/- 18 min for the MPE method (p < 0.0001). The MPE
      correlated poorly with the other method (r = 0.74). Antral peak filling time
      correlated poorly (r = 0.47) with transition point, starting index and FABA, but
      somewhat better with the MPE (r = 0.70). Comparing 15-min versus 1-min sampling
      intervals using the MPE, 35% of subjects had values that differed by > or = 7.5
      min and 10% had values differing by > or = 15 min. CONCLUSION: The lag phase
      calculated by the MPE correlated poorly with other methods, and its accuracy was
      limited by the rate of the temporal sampling. The transition point, starting
      index and FABA all highly correlated with each other; the latter is a
      particularly reliable physiological indicator and is easily quantified using a
      small-bowel TAC.

PMID- 8862300
TI  - Gastric emptying in early noninsulin-dependent diabetes mellitus.
AB  - The aims of this study were to determine in early noninsulin-dependent diabetes
      mellitus (NIDDM): (a) the prevalence of disordered gastric emptying of glucose;
      (b) the relationship between the blood glucose response to an oral glucose load
      and gastric emptying; and (c) the relationship between appetite and gastric
      emptying. METHODS: Sixteen patients (ages 39-79 yr) with recently diagnosed NIDDM
      consumed 350 ml water containing 75 g glucose and 99mTc-sulfur colloid while
      sitting in front of a gamma camera. Blood glucose concentrations were monitored
      immediately before and after the drink. Hunger and fullness were evaluated using
      visual analog scales. The results were compared to those obtained in 13 normal
      subjects of similar age and body mass index. All patients and control subjects
      were white and non-Hispanic. RESULTS: Gastric emptying was slightly slower in the
      NIDDM patients when compared to the control subjects (retention at 180 min 15.9
      +/- 2.3% versus 3.8 +/- 1.0%, p < 0.001), but there was no significant difference
      in the 50% emptying time between the two groups. In the NIDDM patients, there was
      an inverse relationship between the magnitude of the increase in the blood
      glucose concentration and gastric emptying, e.g., between the area under the
      curve for blood glucose from 0-60 min and the intragastric retention of the drink
      at 60 min (r = -0.60, p < 0.05). In the NIDDM patients, fullness was greater (p <
      0.005) both before and after the drink, and the score for hunger at 30 min was
      inversely related to the rate of gastric emptying (r = -0.52, p < 0.05).
      CONCLUSION: In patients with early NIDDM, gastric emptying of 75 g glucose is
      similar to that of normal subjects and is a significant determinant of the
      glycemic response.

PMID- 8862301
TI  - Interpretation of captopril transplant renography using a feed forward neural
      network.
AB  - Severe renal artery stenosis (RAS) is a relatively uncommon complication after
      renal transplantation but is a curable cause of hypertension, which demands
      reliable early diagnosis to reduce morbidity, mortality and graft loss. Captopril
      renography has been used for a number of years as a method of detecting RAS but
      controversy still exists as to the diagnostic accuracy of this test and as to the
      most appropriate interpretation criteria with which to establish a positive
      result. METHODS: This report presents the results of using artificial neural
      networks to impartially assess these interpretation criteria. Data comprised 31
      99mTc-MAG3 captopril renography investigations undertaken on hypertensive renal
      transplant patients with a suspected diagnosis of RAS. Each renogram study was
      correlated with an arteriogram as the "gold standard". Training of the network
      was performed using the round-robin technique. RESULTS: An accuracy of 95% could
      be achieved by considering perfusion index, time-to-peak activity, accumulation
      index and excretion index for both pre- and post-challenge studies. This varied
      as the parameters were either included or excluded. CONCLUSION: Artificial neural
      network analysis is a useful technique to evaluate the most appropriate criteria
      for interpreting captopril transplant renography investigations.

PMID- 8862302
TI  - Baseline and postcaptopril renal blood flow measurements in hypertensives
      suspected of renal artery stenosis.
AB  - Renal blood flow (RBF) measurements using first-pass radionuclide angiography
      with DTPA, a glomerularly filtered agent, failed to show significant differences
      between normal and stenotic kidneys. Since MAG3 is an ideal agent for the study
      of RBF, this agent might be an attractive alternative tracer to detect
      differences in RBF. METHODS: An angiographically controlled prospective study was
      performed in 48 hypertensive patients, in whom a diagnosis of renovascular
      hypertension was suspected on clinical grounds. The study was done to determine
      whether RBF measurements using first-pass radionuclide angiography with 99mTc
      MAG3 could be helpful in the diagnostic work-up of the patients. Additionally,
      the study was done before and after ACE-inhibition. RESULTS: On renal
      angiography, 29 patients showed to have normal renal arteries (50 patients had
      normal kidneys and 8 patients had small kidneys). Nineteen patients had renal
      artery stenosis (13 uni- and 6 bilateral disease). In the patients with normal
      kidneys, the mean value of RBF measurements ranged from 10.5% to 10.9% of cardiac
      output. Only small stenotic and small kidneys with normal renal arteries showed a
      significant reduced baseline RBF as compared with normal kidneys (both p < 0.05);
      this difference disappeared after ACE-inhibition only for the small kidneys with
      normal renal arteries. In patients with stenosed kidneys, RBF tended to be
      reduced both at baseline and after captopril, but the differences with normal
      kidneys were not statistically significant. After ACE-inhibition RBF increased in
      the majority of kidneys, but postcaptopril RBF data did not differ significantly
      from those at baseline. CONCLUSION: RBF measurements using first-pass
      radionuclide angiography with 99mTc-MAG3, either before or after ACE-inhibition,
      cannot reliably discriminate between patients with essential hypertension and
      patients with renal artery stenosis.

PMID- 8862303
TI  - Imaging osteomyelitis with streptavidin and indium-111-labeled biotin.
AB  - Animal studies of infection imaging by a two-step protocol have shown that
      important improvements in target to nontarget ratios are possible. In this
      protocol, unlabeled streptavidin is administered and allowed sufficient time to
      accumulate in the lesion, probably by nonspecific processes, and to clear
      elsewhere. Thereafter, 111Inbiotin is administered. A fraction of the labeled
      biotin may be retained in the lesion because of biotin's high affinity for
      streptavidin while most of the activity is cleared through the kidneys. METHODS:
      Radioscintigraphy with unlabeled streptavidin followed with 111Inlabeled biotin
      was performed in 15 patients with chronic osteomyelitis. As controls, each
      patients received either 111In-labeled biotin without the preadministration of
      streptavidin or 111In-labeled nonspecific IgG. RESULTS: Regions of focal uptake
      were identified in all patients receiving streptavidin followed by radiolabeled
      biotin as early as 10 min postadministration of radioactivity, and retention of
      label was evident through 24 hr. Coincident regions of abnormal accumulation were
      apparent with 111In-IgG, but only in delayed images. Moreover, with 111In-biotin
      alone, without the preadministration of streptavidin, focal accumulations were
      detected in areas similar to that identified with the two-step protocol.
      Although, these observations were only in the earliest images. CONCLUSION: The
      results of this preliminary clinical investigation suggest that a two-step
      protocol with unlabeled streptavidin and radiolabeled biotin may be an
      alternative for the detection of infection.

PMID- 8862304
TI  - Evaluation of sequential thallium and gallium scans of the chest in AIDS
      patients.
AB  - With decreasing incidence of pneumocystis carinii pneumonia (PCP) in AIDS as a
      result of prophylactic regimens, there is a higher incidence of tuberculosis
      (TB), mycobacterium avii complex (MAC), kaposi sarcoma and malignant lymphoma.
      There is a need for differentiating these various pathological entities. The
      purpose of this study was for a retrospective evaluation of sequential thallium
      and gallium scans in AIDS patients for differentiating intrathoracic kaposi
      sarcoma from malignant lymphoma and opportunistic infections. METHODS: A total of
      181 patients had both studies completed between March 1992 and May 1994. The
      final diagnosis was verified only in 83 patients. Results were correlated with
      the CD4 counts, bronchoscopic and chest radiograph findings. RESULTS: In patients
      with pulmonary kaposi sarcoma and no opportunistic infections (19 patients), a
      thallium-positive, gallium-negative pattern was detected in 17 patients with a
      sensitivity of 89%. In the presence of kaposi sarcoma plus opportunistic
      infections, this pattern was only detected in 7 of 19 patients (sensitivity
      dropped to 37%). In 45 patients with opportunistic infections and no kaposi
      sarcoma, only two false-positive findings were found in patients with cytomegalic
      virus pneumonia for a specificity of 96%. For the whole group of 83 patients,
      sensitivity was 63%; specificity 95%; positive predictive value 92%; accuracy
      81%; and negative predictive value 75%. CONCLUSION: A thallium-positive, gallium
      negative pattern in AIDS patients has a high specificity for the diagnosis of
      kaposi sarcoma, however, the sensitivity dropped from 89% to 37% in the presence
      of opportunistic infections.

PMID- 8862305
TI  - Radiation absorbed dose estimates for [1-carbon-11]-glucose in adults: the
      effects of hyperinsulinemia.
AB  - As preparation for studies of blood-brain glucose transport in diabetes mellitus,
      radiation absorbed dose estimates from intravenous administration of [1-(11)C]
      glucose for 24 internal organs, lens, blood and total body were calculated for
      three physiologic conditions: euinsulinemic euglycemia, hyperinsulinemic
      euglycemia and hyperinsulinemic hyperglycemia. METHODS: Cumulated activities in
      blood, Insulin-independent and insulin-dependent compartments were calculated
      from blood time-activity curves in normal human volunteers and macaques.
      Apportionment of cumulated activity to individual organs in insulin-dependent and
      insulin-independent compartments was based on previously published data. Absorbed
      doses were calculated with the computer program MIRDOSE 3 for the 70-kg adult
      phantom. S for blood was calculated separately. RESULTS: The heart wall lungs and
      spleen were the organs receiving the highest dose. The effect of hyperinsulinemia
      was demonstrated by the increase in absorbed dose to the muscle, heart and blood
      with a decrease to other internal organs. This effect was more pronounced during
      hyperinsulinemic hyperglycemia. Hyperinsulinemia produced a decrease in effective
      dose due to the decrease in cumulated activity in organs with specified weighting
      factors greater than 0.05. CONCLUSION: The effective dose per study for [1-(11)C]
      glucose is comparable to that reported for 2-deoxy-[2-(18)F]-glucose.

PMID- 8862306
TI  - Spontaneous regression of intracranial arteriovenous malformation on PET.
AB  - We report a case of spontaneous regression of intracranial arteriovenous
      malformation (AVM) detected by PET in a 57-yr-old woman who had suffered repeated
      ruptures of the AVM at 28, 30 and 31 yr of age associated with pregnancy. The
      rupture at this hospitalization was the most critical, and after repeated
      ruptures for 1 mo, the AVM regressed spontaneously. The decreased cerebral blood
      volume (CBV) in the AVM indicated regression. The flow-to-volume (CBF/ CBV)
      ratios surrounding the AVM increased. The metabolic rate for oxygen (CMRO2) did
      not correlate with her improved neurological status, and an imbalance between CBF
      and CMRO2 was recognized.

PMID- 8862307
TI  - Extensive photopenic osteomyelitis.
AB  - We present a case of a previously healthy child whose osteomyelitis and septic
      arthritis resulted in unusually extensive photopenia on bone scintigraphy. Uptake
      was absent in the humeral shaft and proximal epiphysis and decreased in the
      proximal physis. The subsequent complicated clinical course, including surgical
      interventions, and bone scans is described.

PMID- 8862308
TI  - Detection of impaired fatty acid metabolism and dyskinesis in hypertrophic
      cardiomyopathy with iodine-123-BMIPP.
AB  - Metabolic imaging using 123I-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic
      acid (BMIPP) and Fourier phase analysis of gated blood-pool data were performed
      in a 60-yr-old woman with idiopathic hypertrophic cardiomyopathy. Dyskinetic wall
      motion was identified as a markedly delayed phase angle in the left ventricular
      apex, which was well perfused but highly hypertrophied like other ventricular
      segments. Fatty acid imaging, however, clearly demonstrated highly reduced
      activities in the apex, although there were no abnormalities in regional systolic
      function or in 201TI uptake in other hypertrophied regions. Contrast left
      ventriculography revealed a midventricular collapse of the left ventricle at end
      systole due to markedly hypertrophied ventricular walls and dyskinesis at the
      apex. Thus, dyskinetic wall motion in the apex closely correlated not only with
      cardiac hypertrophy but also with impaired fatty acid uptake. These findings were
      unrelated to the myocardial perfusion state per se. Fatty acid imaging using
      BMIPP may contribute to the detection of myocyte degeneration not visible using
      conventional imaging modalities. It may also provide etiological information on
      regional dysfunction in hypertrophic cardiomyopathy.

PMID- 8862309
TI  - Pseudostripe sign in lobar collapse.
AB  - The stripe sign in perfusion lung scanning refers to an area of focal
      hypoperfusion that fails to extend to the pleural surface, leaving a peripheral
      rim of perfused parenchyma. Although experimental evidence suggests that the
      stripe sign is caused by central pulmonary emphysema, we report a case of an
      identical perfusion defect related to a completely collapsed left lower lobe.
      This etiology should be considered in the differential diagnosis of the stripe
      sign.

PMID- 8862310
TI  - Abnormal colonic accumulation of fluorine-18-FDG in pseudomembranous colitis.
AB  - A 51-yr-old man with a history of pancreatic carcinoma was studied with
      [18F]fluorodeoxyglucose ([18F]FDG) and PET as part of staging for residual
      disease after chemotherapy. The PET study was performed during a clostridium
      difficile-associated diarrheal illness. Striking [18F]FDG uptake was demonstrated
      in the wall of the colon over its entire length. Clostridium difficile associated
      diarrhea and mechanisms of [18F]FDG uptake in normal and abnormal tissues are
      briefly reviewed and a mechanism for FDG uptake in this patient is postulated.

PMID- 8862311
TI  - Abnormal iodine-123-MIBG images in healthy volunteers.
AB  - We have encountered two healthy volunteers with significant reductions of
      myocardial [123I]MIBG (metaiodobenzylguanidine) uptake and rapid clearance. In
      one of these subjects (a 31-yr-old man), we performed additional examinations to
      clarify the mechanism of the abnormal myocardial MIBG uptake. There was no
      abnormality on orthostatic test, maximal exercise test (bicycle ergometer) or in
      plasma norepinephrine concentration. Nevertheless, power spectral analysis (PSA)
      of heart rate variability revealed that the percent low frequency component
      (%LF), an index of sympathetic nerve activity, was increased. Furthermore,
      [123I]MIBG scintigraphy after oral administration of an alpha 2 agonist
      (guanabenz acetate; 4 mg) demonstrated that myocardial uptake and clearance of
      MIBG returned to normal, as did the %LF. These results suggest that reduced
      uptake and rapid clearance of myocardial MIBG in this subject was strongly
      related to the increased release of norepinephrine from sympathetic nerve
      terminals due to augmented sympathetic activity. This subject illustrated that
      unsuspected, subclinical variants of normal or abnormal sympathetic functions may
      pose a diagnostic pitfall in interpretating myocardial MIBG images.

PMID- 8862312
TI  - Bartter's syndrome: renal scintigraphic appearance after captopril
      administration.
AB  - We report a case of Bartter's syndrome, a rare disease characterized by
      hypokalemia, increased plasma renin and angiotensin II levels with normal blood
      pressure. During the diagnostic work-up, the patient had renal scintigraphy in
      baseline and after captopril administration. Pharmacological blockade of the
      renin-angiotensin system with captopril resulted in bilateral and symmetrical
      renal abnormalities (increase of parenchymal transit time, time to maximum
      activity and retained cortical activity, with cortical trapping of the
      radiopharmaceutical). Baseline scintigraphy was normal. The findings are
      consistent with Bartter's syndrome pathogenesis. Captopril renography may be
      useful to differentiate Bartter's syndrome from other covert causes of
      hypokalemia.

PMID- 8862313
TI  - False-positive iodine-131 whole-body scans due to cholecystitis and sebaceous
      cyst.
AB  - False-positive whole-body 131I scans are not frequent but have serious
      consequences in the management of patients with thyroid cancer. They can be
      classified in four main groups: elimination of iodine in body fluids, infection
      or inflammation, cysts or transudates and nonthyroid tumors. We report on two
      patients with false-positive post-therapy 131I scans. The first patient had
      uptake projected in the right pelvic area which was later proven to be a large
      gluteal sebaceous cyst. The second patient had uptake in the gallbladder area
      that did not disappear after 131I treatment; she underwent exploratory laparotomy
      which revealed extensive chronic cholecystitis. These cases illustrate two new
      causes of false-positive 131I whole-body scans (sebaceous cyst and
      cholecystitis), which highlights two mechanisms (elimination in body fluid and
      inflammation).

PMID- 8862314
TI  - Cellular basis of ECD brain retention.
AB  - Clinical observations have shown discrepancies between ECD and HMPAO regional
      cerebral perfusion, particularly in brain tumors and during stroke recovery. We
      investigated the nature of the process(es) involved in ECD accumulation in vitro
      at the cellular level. METHODS: Time course incorporation of ECD was studied in a
      fast-growing human premonocytic line, U937, in a human astrocytic-derived cell
      line, U373, and a human hybridized endothelial cell line, EaHy926. Cells were
      further used in experiments aiming to correlate esterase activity and ECD
      retention. RESULTS: Significant differences in ECD retention between these cell
      lines were observed: %UECD (cpm cells/cpm standard of injected) plateaued within
      2 hr in all cases but %UECD was significantly higher in U937 cells (25.1 +/- 3.9%
      at 120 min) than in the other cell lines (6.1 +/- 0.7% and 8.2 +/- 2.0% at 120
      min for U373 and EaHy926, respectively). Contrary to what we expected, total
      cellular esterase activity (EATOT) was inversely correlated to %UECD.EATOT was 5
      fold lower in U937 cells than in U373 and 20-fold lower than in EaHy926. Thus, we
      compared the membranar to the cytosolic esterase activity of U937 and analyzed
      the influence of temperature and diisopropylfluorophosphate (DFP, an inhibitor of
      cytosolic esterase activity) on both ECD retention and enzymatic activities. When
      cells were exposed to DFP, %UECD was reduced by 80%; while when cells were
      maintained at 4 degrees C, %UECD continuously increased, corresponding to a
      passive diffusion since both cytosolic and membranar esterase activities were
      inhibited. CONCLUSION: For optimal uptake of ECD, the membranar fraction of the
      esterase activity has to be low, while, in contrast, the cytosolic fraction of
      the esterase activity plays an important role in ECD cell retention. ECD-SPECT is
      likely able to reflect regional cerebral blood flow in normal and pathological
      states accurately, but in the event of unusual observations, the membranar
      esterase activity should be considered to explain reduced ECD retention.

PMID- 8862315
TI  - Assessment of antioxidative ability in brain: technetium-99m-meso-HMPAO as an
      imaging agent for glutathione localization.
AB  - To visualize the regional localization of glutathione (GSH) in the brain, the
      relationship between the concentrations of tissue GSH and uptake of [99mTc]meso
      hexamethyl propyleneamine oxime ([99mTc] meso-HMPAO) or [99mTc]d,l-hexamethyl
      propyleneamine oxime ([99mTc]d,l-HMPAO) was studied in mice. METHODS: The uptake
      of [99mTc]meso-HMPAO in the mouse brain was decreased to 35% of control
      paralleling the decrease in GSH content by pre-loading of diethyl maleate (DEM),
      an agent to reduce GSH. In contrast, pre-treatment with DEM scarcely affected the
      99mTc-d,l-HMPAO uptake in the brain. RESULTS: The DEM treatment decreased the GSH
      content in liver, kidney, spleen, fat and lung but did not affect the uptake of
      [99mTc]meso-HMPAO in those tissues except lung. The images of rat brain acquired
      with a gamma camera showed a significant reduction of [99mTc]meso-HMPAO uptake by
      DEM treatment. CONCLUSION: Technetium-99m-meso-HMPAO may be a potential tool to
      assess GSH content and to estimate antioxidative ability in the brain.

PMID- 8862316
TI  - Coronary flow and flow reserve by PET simplified for clinical applications using
      rubidium-82 or nitrogen-13-ammonia.
AB  - To validate routine, noninvasive determination of absolute myocardial perfusion
      and coronary flow reserve (CFR), cardiac PET was performed in animals using a
      simplified imaging protocol, high-dose dipyridamole and a simplified quantitative
      algorithm specific for 82Rb and 13N-ammonia. METHODS: One hundred thirty-five PET
      scans were obtained in eight dogs after intravenous 13N-ammonia or 82Rb using
      serial dynamic PET or a simple two-image dataset. A simple flow model using the
      two-image dataset was developed for each radionuclide to account for varying
      arterial input function, flow-dependent myocardial extraction and increased
      permeability surface area (PS) product due to capillary recruitment at high flows
      not incorporated into previous models. Myocardial perfusion by the simple model
      was compared to standard, complete, two-compartment kinetic models validated by
      comparison to electromagnetic flow meter. RESULTS: For 13N-ammonia, myocardial
      perfusion by the simple PET model correlated with that by complete compartmental
      analysis of multiple serial PET images with r = 0.94, slope = 0.96; CFR by
      compartmental analysis correlated with CFR by electromagnetic flow meter with r =
      0.94, slope = 0.97. For 82Rb, myocardial perfusion determined by the simple model
      correlated with that determined by complete compartmental analysis of multiple
      serial PET images with r = 0.98, slope = 1.06; CFR determined by compartmental
      analysis correlated with CFR by electromagnetic flow meter with r = 0.88, slope =
      1.13. CONCLUSION: A simplified PET protocol using 13N-ammonia or 82Rb and simple
      flow models provide noninvasive measurement of CFR up to six times baseline flow
      throughout the heart and diagnostic image quality for routine clinical
      application.

PMID- 8862317
TI  - Re-evaluation of myocardial FDG uptake in hyperglycemia.
AB  - Myocardial [18F] fluorodeoxyglucose (FDG) uptake depends on several metabolic
      variables in vivo. The effect of different levels of experimentally induced
      hyperglycemia on myocardial FDG uptake was examined. METHODS: FDG uptake was
      studied in young Donryu rats 1 hr after intravenous injection under various
      pretreatments that increased serum glucose levels. Serum samples were analyzed
      for glucose, insulin and free fatty acids. Myocardial distribution of FDG was
      examined with autoradiography. RESULTS: Administration of glucose (n = 42),
      triiodothyronine (n = 7), epinephrine (n = 7), dehydroascorbic acid (n = 5) and 4
      mg streptozotocin (Szt, n = 10) increased glucose levels to 120-200 mg/dl.
      Dexamethasone (Dex, n = 34) and 6 mg Szt (n = 6) increased glucose levels to 200
      450 mg/dl. Myocardial FDG uptake increased proportionately with increases in
      serum glucose level up to 200 mg/dl. In severe hyperglycemia (serum glucose: 200
      450 mg/dl), however, the FDG uptake decreased and did not correlate with blood
      glucose level. A study of fractional FDG uptake calibrated by the arterial FDG
      curve confirmed the same results. Heterogeneous distribution of FDG was observed
      in the myocardium, both in fasting and in severe hyperglycemic conditions. The
      pattern of FDG uptake by skeletal muscles was similar to that of the myocardium,
      although the uptake was lower than that in the myocardium. Changes in insulin and
      free fatty acids levels could not explain the FDG uptake pattern in severe
      hyperglycemia. Blood FDG uptake level remained constant regardless of glucose
      level. CONCLUSION: Hyperglycemia induced a biphasic pattern of myocardial FDG
      uptake, common with skeletal muscles. The understanding of myocardial FDG uptake
      characteristics and their dependence on blood glucose is helpful in interpreting
      myocardial FDG-PET images.

PMID- 8862318
TI  - Derivation of input function from FDG-PET studies in small hearts.
AB  - The extraction of pure arterial time-activity curves (TACs) from dynamic PET
      images of a small animal heart using factor analysis of dynamic structures (FADS)
      was found to be unsuccessful due to the small size of the cardiac chamber that
      causes extensive mixture of TACs of different structures. METHODS: In this study,
      we used digital phantoms of the left ventricle (LV cavity size: 1-2 cm) and small
      monkey (LV cavity size: approximately 2 cm) dynamic FDG PET studies to evaluate
      FADS for extracting the pure blood-pool TACs by adding a single blood sample
      (taken at a late scan time) constraint. RESULTS: In the digital phantom studies,
      spillover fractions in the extracted blood-pool TACs using FADS without a blood
      sample constraint (FADS(-)) and with a blood sample constraint (FADS(+)) were 3%
      91% and < 3%, respectively. In the monkey studies (n = 4), FADS(+) extracted
      blood-pool TACs matched well with the arterialized well counter measurements (%
      differences of curve integration; FADS(-) < 82%; FADS(+) < 9%). The
      microparameters (K1*, k2*, k3*, k4*) and macroparameters (Knlr), obtained from
      the FADS(+) blood-pool TACs, were similar to those obtained from plasma samples
      in a three-compartment model fitting (% differences of Knlr:phantom studies < 5%;
      monkey studies < 9%). CONCLUSION: The FADS technique with a single-blood sample
      has the potential to extract the pure blood-pool TACs directly from dynamic PET
      images of a small animal without multiple blood sampling, region of interest
      definition or spillover correction.

PMID- 8862319
TI  - Quantitation of myocardial fatty acid metabolism using PET.
AB  - Abnormalities of fatty acid metabolism in the heart presage contractile
      dysfunction and arrhythmias. This study was performed to determine whether
      myocardial fatty acid metabolism could be quantified noninvasively using PET and
      1-(11)C-palmitate. METHODS: Anesthetized dogs were studied during control
      conditions; during administration of dobutamine; after oxfenicine; and during
      infusion of glucose. Dynamic PET data after administration of 1-(11)C-palmitate
      were fitted to a four-compartment mathematical model. RESULTS: Modeled rates of
      palmitate utilization correlated closely with directly measured myocardial
      palmitate and total long-chain fatty acid utilization (r = 0.93 and 0.96,
      respectively, p < 0.001 for each) over a wide range of arterial fatty acid levels
      and altered patterns of myocardial substrate use (fatty acid extraction fraction
      ranging from 1% to 56%, glucose extraction fraction from 1% to 16% and myocardial
      fatty acid utilization from 1 to 484 nmole/g/ min). The percent of fatty acid
      undergoing oxidation could also be measured. CONCLUSION: The results demonstrate
      the ability to quantify myocardial fatty acid utilization with PET. The approach
      is readily applicable for the determination of fatty acid metabolism
      noninvasively in patients.

PMID- 8862320
TI  - Technetium-99m-DMSA renal cortical scintigraphy to detect experimental acute
      pyelonephritis in piglets: comparison of planar (pinhole) and SPECT imaging.
AB  - The purpose of this study was to directly compare the sensitivity and specificity
      of SPECT and pinhole imaging for the detection of acute pyelonephritis using
      histology as the standard of reference. METHODS: Bilateral vesicoureteral reflux
      of infected urine was induced in 16 piglets (32 kidneys) by unroofing the
      intravesical ureter and subsequently instilling a broth culture of E. coli into
      the bladder. DMSA scans were obtained by both pinhole and SPECT techniques at 24
      hr (4 piglets), 48 hr (5 piglets), 72 hr (4 piglets) and 10 days (3 piglets)
      after instillation of bacteria into the bladder. Kidneys were harvested
      immediately after scintigraphy for histopathologic examination. Results of the
      SPECT images, pinhole images and histologic findings were interpreted
      independently in a blinded fashion. The images of each kidney were classified as
      positive or negative for pyelonephritis regardless of the severity and number of
      lesions. To evaluate accuracy of SPECT and pinhole imaging for the detection of
      individual lesions, each kidney was arbitrarily divided into three zones (upper,
      middle and lower). Image findings were then compared with the pathology results
      for the presence or absence of pyelonephritis in each zone. RESULTS:
      Histopathology revealed pyelonephritis in 24 of 32 kidneys (58 of 96 zones). The
      sensitivity of the DMSA scan for detection of affected kidneys was 92% for SPECT
      and 83% for pinhole; overall accuracy was 88% for both. The sensitivity of SPECT
      for the detection of affected renal zones was slightly better than pinhole
      imaging (91% compared with 86%), but its specificity was lower (82% compared with
      95%) resulting in a similar accuracy. Excluding four piglets where scans were
      obtained within 24 hr after instillation of bacteria into the bladder, the
      sensitivity of SPECT and pinhole for the detection of affected kidneys were 95%
      and 90%, respectively. Their overall accuracy were 96% and 92%. In this subgroup,
      the sensitivity, specificity and accuracy of SPECT for the detection of involved
      zones were 96%, 95% and 96%, respectively. The corresponding values for pinhole
      imaging were 90%, 95% and 92%, respectively. CONCLUSION: Although the sensitivity
      of SPECT for the detection of acute pyelonephritis is slightly better than
      pinhole DMSA scan, the overall accuracy of these two imaging techniques is
      essentially the same.

PMID- 8862321
TI  - Comparison of technetium-99m-HMPAO and xenon-133 measurements of regional
      cerebral blood flow by SPECT.
AB  - This study compares 99mTc-HMPAO count ratios and derived regional cerebral blood
      flow (rCBF) to 133Xe rCBF ratios and true rCBF (ml/min/100 g), respectively.
      METHODS: Technetium-99m-HMPAO distribution was evaluated in 14 patients and 5
      normal control subjects. Immediately after 133Xe SPECT, subjects received 22 +/-
      4mCi 99mTc-HMPAO, and images were acquired 15 min after injection. rCBF
      (ml/min/100 g, 133Xe) or regional count density (99mTc-HMPAO) were extracted from
      24 ROI located 6 cm above the cantho-meatal line. These data were also normalized
      to global cerebral blood flow (gCBF) for 133Xe or to global count density (gCD)
      for 99mTc-HMPAO. Technetium-99m-HMPAO ROI data also were expressed in units of
      ml/min/100 g by relating gCD to gCBF. Comparisons between 133Xe and 99mTc-HMPAO
      were evaluated using a Bonferroni-corrected paired t-test and by linear
      regression analysis. RESULTS: Profile plots demonstrated agreement in the pattern
      of relative distribution between rCBF ratios (133Xe) and count density ratios
      (99mTc-HMPAO). Regression analysis indicated a significant correlation (r =
      0.78), with a modest slope (0.52) and a large intercept (0.48). A closer
      correlation (r = 0.92) was found for the comparison between rCBF (133Xe) and
      derived 99mTc-HMPAO rCBF. The slope was closer to one (0.82) and the intercept
      closer to zero. This relationship was also examined during high rCBF after a
      subset of these subjects (n = 7) was injected intravenously with 1 g
      acetazolamide. Again, profile plots and regression analysis demonstrated
      agreement in the pattern of distribution (ratios) between 133Xe and 99mTc-HMPAO
      (r = 0.66). However, the slope was reduced and the intercept increased relative
      to resting data. Absolute flow correlations showed some improvement relative to
      the ratio data (r = 0.77). CONCLUSION: The distribution of 99mTc-HMPAO is
      linearly related to rCBF measured by 133Xe SPECT, although our data suggest that
      99mTc-HMPAO mildly underestimates rCBF above 80 ml/min/100 g. These results are
      similar to our previous comparison of 99mTc-ECD and 133Xe.

PMID- 8862322
TI  - Optimal number of views in 360 degrees SPECT imaging.
AB  - This study examined SPECT-reconstructed image quality as a function of the number
      of views, and determined the minimum number of views necessary to remove aliasing
      artifacts in 360 degrees SPECT. METHODS: Computer simulation was performed using
      a two-dimensional Shepp-Logan head phantom and a high-resolution parallel-beam
      collimator with and without photon attenuation. RESULTS: In 360 degrees SPECT,
      aliasing artifacts were reduced by changing the number of views from an even
      number 16 to its neighboring odd numbers 15 or 17, from 32 to 31 or 33 and from
      64 to 63 or 65. Image quality of 15 or 17 views, 31 or 33 views and 63 or 65
      views was similar to that of 32, 64 and 128 views, respectively. CONCLUSION:
      Replacing an even number of views by its neighboring odd numbers in 360 degrees
      SPECT significantly decreased aliasing artifacts. Thirty-one or 33 views are
      sufficient to remove most of the aliasing artifacts in 360 degrees SPECT with a
      matrix of 64 x 64 pixels. This method can be applied to fast 360 degrees SPECT
      since fewer views are used.

PMID- 8862323
TI  - Differential diagnosis of a tender goiter.
AB  - Subacute thyroiditis is generally felt to have a viral etiology, and the
      diagnosis is usually obvious when the patient presents with a diffusely enlarged
      and very tender thyroid gland associated with elevated free T4 levels, elevated
      sedimentation rate, low radioiodine uptake and/or nonvisualization on scan and
      often some systemic symptoms. Subacute thyroiditis can be unilateral or focal
      (1,2). Corticosteroids are very effective in relieving symptoms of subacute
      thyroiditis, often within 24 hr (3). Three patients are presented where the
      initial impression was subacute thyroiditis, there was a clinical response to
      prednisone, but none of the patients actually had subacute thyroiditis.

PMID- 8862324
TI  - From knowledge to action: improving drug prescribing.

PMID- 8862325
TI  - Hepatitis B in Australia: on course for universal vaccination.

PMID- 8862326
TI  - The new genetics: legal and ethical implications for medicine.

PMID- 8862327
TI  - Haematopoietic growth factors and chemotherapy: new horizons.

PMID- 8862328
TI  - Benzodiazepine prescribing in a Sydney teaching hospital.
AB  - OBJECTIVES: To determine the pattern of benzodiazepine prescribing in hospital
      and at discharge in relation to prior benzodiazepine therapy. DESIGN: Patient
      interview within 48 hours of admission to determine benzodiazepine, alcohol and
      other psychotropic drug use before admission and review of medical records after
      discharge to document drugs prescribed in hospital and at discharge. SETTING:
      Tertiary teaching hospital, January to August 1995. RESULTS: 1453 patients (mean
      age, 60 [SD, 19] years; 52.7% female) were interviewed; 277 patients (19.1%) were
      taking benzodiazepines regularly (one or more doses per week) before admission.
      Of these, 28.5% did not have benzodiazepine therapy continued while in hospital
      and 63.9% did not receive benzodiazepines at the time of discharge. Of the
      remaining 1176 patients (those not previously taking benzodiazepines), 277
      (23.6%) were prescribed them for the first time in hospital and 5.3% received
      benzodiazepines at the time of discharge. Older age, female sex, marital status
      (single, divorced or widowed) and the use of antidepressants and Schedule 8
      narcotic analgesics were all statistically significant predictors of
      benzodiazepine use before admission, but alcohol consumption was not.
      CONCLUSIONS: A substantial number of patients do not have their benzodiazepine
      therapy continued in hospital and at the time of discharge, and are thus at risk
      of developing benzodiazepine withdrawal syndromes, including delirium. A small
      but clinically significant number of patients who do not usually take
      benzodiazepines receive them at the time of discharge and may be at risk of
      becoming long term users.

PMID- 8862329
TI  - Premature mortality in aboriginal adults in the Northern Territory, 1979-1991.
AB  - OBJECTIVE: To identify important causes of premature mortality among Aboriginal
      adults in the Northern Territory (NT), 1979-1991. METHODS: All deaths of NT
      Aboriginal residents aged 15-64 years which occurred in the NT between 1979 and
      1991 and which were recorded by the Registry of Births, Deaths and Marriages were
      included. Standardised mortality ratios (SMRs) were used to compare the number of
      deaths observed among Aboriginals in the NT to those expected, based on overall
      Australian rates. Years of potential life lost before age 65 (YPLL65) were
      estimated for specific causes of death. RESULTS: Aboriginal women (overall SMR,
      5.5) and Aboriginal men (SMR, 4.7) experienced a high burden of excess mortality
      from almost every cause of death. This excess increased over time, especially for
      Aboriginal women. Among Aboriginal men, the most important causes of premature
      death were motor vehicle accidents (11% of excess deaths and 17% of YPLL65),
      ischaemic heart disease (10% of excess deaths and 10% of YPLL65), pneumonia and
      influenza (8% of excess deaths and 6% of YPLL65), and homicide (7% of excess
      deaths and 8% of YPLL65). For Aboriginal women, the most important causes
      included homicide (7% of excess deaths and 11% of YPLL65), chronic obstructive
      pulmonary disease (10% of excess deaths and 5% of YPLL65), rheumatic heart
      disease (7% of excess deaths and 8% of YPLL65), and ischaemic heart disease (6%
      of excess deaths and 5% of YPLL65). CONCLUSIONS: The wide variety of causes of
      excess mortality will require an equally wide variety of solutions, both medical
      and non-medical, and a long term commitment will be necessary to achieve
      reductions in premature mortality among NT Aboriginal adults.

PMID- 8862330
TI  - Changing epidemiology of Ross River virus disease in South Australia.
AB  - OBJECTIVE: To investigate changes in epidemiology and symptoms of Ross River
      virus (RRV) disease in South Australia. DESIGN: Longitudinal questionnaire-based
      survey of notified cases from one to 36 months after infection. SUBJECTS: All
      patients with recent serologically confirmed RRV infection notified to the
      Communicable Disease Control Unit, South Australian Health Commission, between 1
      October 1992 and 30 June 1993. OUTCOME MEASURES: Sociodemographic data, source of
      infection, symptoms and ability to carry out daily activities (at onset of
      illness and at time of questionnaire, up to 36 months after infection), symptom
      duration, economic impact of the illness, cases recovery time, factors predictive
      of delayed recovery. RESULTS: Information was obtained on the acute illness from
      698 of the 821 subjects and at 15 months after infection from 436. At 15 months,
      51% of respondents still had joint pain and 45% had persistent tiredness and
      lethargy. Other common symptoms included myalgia (34%), lymphadenopathy (25%),
      headache (23%) and depression (22%). These symptoms were still common 30 months
      after infection. Increasing age was the only statistically significant predictor
      of delayed recovery. Infections were acquired across the State, away from
      previously recognised RRV-endemic areas. CONCLUSIONS: For many people, RRV
      disease is debilitating, with long term symptoms similar to those of chronic
      fatigue syndrome. The geographic range of the infection has expanded in SA.

PMID- 8862331
TI  - Visceral angioedema related to treatment with an ACE inhibitor.
AB  - For more than five years, a patient suffered recurrent episodes of abdominal pain
      accompanied by diarrhoea, nausea and vomiting. An angiotensin converting enzyme
      (ACE) inhibitor causing visceral oedema was eventually implicated.

PMID- 8862332
TI  - The incidence of hepatitis B infection in Australia: an epidemiological review.
AB  - Hepatitis B virus (HBV) infection in Australia remains a significant problem
      despite the availability of an inexpensive vaccine. National information about
      incidence, prevalence, morbidity and the extent of vaccine coverage is
      incomplete; improved surveillance would allow for better targeting and evaluation
      of prevention activities. Our estimates indicate that 75%-90% of cases of
      vertical transmission of HBV are preventable through vaccination of newborns
      whose mothers are carriers.

PMID- 8862333
TI  - Confidentiality and the AMA's new code of ethics: an imprudent formulation?
AB  - The Australian Medical Association's modification of the absolute rule requiring
      confidentiality in the doctor-patient relationship may be seen as a coming-of-age
      of the organisation. However, the change remains controversial: there are no
      guidelines as to when breaches of confidentiality are justified; and it is
      uncertain whether the new formulation will actually protect the public interest.

PMID- 8862334
TI  - A template for diagnosis and management of musculoskeletal diseases.

PMID- 8862335
TI  - Osteoporosis.

PMID- 8862336
TI  - Silicone breast implants: implications for society and surgeons.
AB  - In the last two years, scientific studies have confirmed that there is no
      significant increase in risk of subsequent breast cancer, connective-tissue
      disease or symptoms in women with silicone gel-filled breast implants. Despite
      this evidence, a moratorium (in place since 1992) on the use of these prostheses
      in the United States has been maintained by the pressure of overwhelming
      litigation. At the same time, Australian authorities also announced a moratorium,
      restricting the availability of silicone breast implants. Huge damages awarded by
      United States courts forced Dow Corning, manufacturer of a large percentage of
      breast prostheses, to file for Chapter 11 bankruptcy in May 1995. This
      effectively terminated the major source of implantable silicone for medical use.
      The withdrawal of implantable silicone and other implantable prosthetic material
      will be a significant loss for surgeons and society. This paper will highlight
      the consequences if reasoned scientific data are not relied on by Australian
      courts to assess claims for damages relating to medical devices.

PMID- 8862337
TI  - Successful treatment of serotonin syndrome with chlorpromazine.

PMID- 8862338
TI  - Antidepressant co-prescribing--how often does it occur?

PMID- 8862339
TI  - Polyvalent vaccines and the national immunisation schedule.

PMID- 8862340
TI  - Adverse hepatic events associated with drug therapy.

PMID- 8862341
TI  - Children's exposure to environmental tobacco smoke in private vehicles.

PMID- 8862342
TI  - Tinea of the skin, hair and nails.

PMID- 8862343
TI  - Analysis of 12 months of blood alcohol levels in patients in an urban emergency
      department.

PMID- 8862344
TI  - Arthritis in Australia: an emerging public health problem.

PMID- 8862345
TI  - Skin-prick test sensitivity to olive pollen.

PMID- 8862346
TI  - Charcot-Marie-Tooth disease and related inherited neuropathies.
AB  - Charcot-Marie-Tooth disease (CMT) was initially described more than 100 years ago
      by Charcot, Marie, and Tooth. It was only recently, however, that molecular
      genetic studies of CMT have uncovered the underlying causes of most forms of the
      diseases. Most cases of CMT1 are associated with a 1.5-Mb tandem duplication in
      17p11.2-p12 that encompasses the PMP22 gene. Although many genes may exist in
      this large duplicated region, PMP22 appears to be the major dosage-sensitive
      gene. CMT1A is the first autosomal dominant disease associated with a gene dosage
      effect due to an inherited DNA rearrangement. There is no mutant gene, but
      instead the disease phenotype results from having 3 copies of a normal gene.
      Furthermore, these findings suggest that therapeutic intervention in CMT1A
      duplication patients may be possible by normalizing the amount of PMP22 mRNA
      levels. Alternatively, CMT1A can be caused by mutations in the PMP22 gene. Other
      forms of CMT are associated with mutations in the MPZ (CMT1B) and Cx32 (CMTX)
      genes. Thus, mutations in different genes can cause similar CMT phenotypes. The
      related but more severe neuropathy, Dejerine-Sottas syndrome (DSS), can also be
      caused by mutations in the PMP22 and MPZ genes. All 3 genes thus far identified
      by CMT researchers appear to play an important role in the myelin formation or
      maintenance of peripheral nerves. CMT1A, CMT1B, CMTX, hereditary neuropathy with
      liability to pressure palsies (HNPP), and DSS have been called myelin disorders
      or "myelino-pathies." Other demyelinating forms, CMT1C and CMT-AR, may be caused
      by mutations of not yet identified myelin genes expressed in Schwann cells. The
      clinically distinct disease HNPP is caused by a 1.5-Mb deletion in 17p11.2-p12,
      which spans the same region duplicated in most CMT1A patients. Underexpression of
      the PMP22 gene causes HNPP just as overexpression of PMP22 causes CMT1A. Thus, 2
      different phenotypes can be caused by dosage variations of the same gene. It is
      apparent that the CMT1A duplication and HNPP deletion are the reciprocal products
      of a recombination event during meiosis mediated through the CMT1A-REPs. CMT1A
      and HNPP could be thought of as a "genomic disease" more than single gene
      disorders. Other genetic disorders may also prove to arise from recombination
      events mediated by specific chromosomal structural features of the human genome
      (102). Further studies on the recombination mechanism of CMT and HNPP might
      reveal the causes of site specific homologous recombination in the human genome.
      The discovery of the PMP22 gene in the 1.5-Mb CMT1A duplication/HNPP deletion
      critical region also suggests that the clinical phenotype of chromosome aneuploid
      syndromes may result from the effect of a small subset of dosage-sensitive genes
      mapping within the region of aneuploidy. The understanding of the molecular basis
      of CMT1 and related disorders has allowed accurate DNA diagnosis and genetic
      counseling of inherited peripheral neuropathies and will make it possible to
      develop rational strategies for therapy. As several loci for CMT2 have been
      identified, the genes responsible for CMT2 will most likely be disclosed using
      positional cloning and candidate gene approaches in the near future.

PMID- 8862347
TI  - Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of
      the literature.
AB  - The true incidence of sarcoidosis in common variable immunodeficiency (CVID) is
      unknown. We report here 8 cases of sarcoidosis among 80 patients with CVID
      followed in our clinics, along with 22 well-documented cases reported in the
      literature. Sarcoidosis, therefore, represents an important entity to consider
      among patients with CVID who exhibit clinical, radiographic, laboratory, and
      biopsy findings compatible with sarcoidosis. Conversely, the diagnosis of CVID
      should be considered in patients with sarcoidosis who do not exhibit the
      characteristic hypergammaglobulinemia and who have a history of recurrent
      infections. Although many features of sarcoidosis are similar in patients with
      CVID to those in patients with sarcoidosis alone, there are many important
      differences. Patients with CVID in whom sarcoidosis develops present with
      hypogammaglobulinemia rather than hypergammaglobulinemia and have a higher
      prevalence of recurrent infections, thrombocytopenia, and splenic involvement.
      Steroids, in most cases, appeared helpful in reducing adenopathy and
      splenomegaly, improving uveitis, lowering serum alkaline phosphatase, and
      reversing hematologic abnormalities. The underlying pathophysiology responsible
      for the association of these 2 disorders in the same patient remains obscure.
      However, as more patients are identified, it may be possible to gain a better
      understanding of the immunologic defect responsible for the dual presentation of
      these 2 relatively uncommon diseases.

PMID- 8862348
TI  - Endocrine implications of human immunodeficiency virus infection.
AB  - Endocrine abnormalities occur frequently in HIV-infected patients. Although the
      majority of endocrine disorders reflect chronic infection, stress, and
      malnutrition, some disorders are characteristic of HIV infection or AIDS and
      deserve particular clinical attention. Identification of HIV patients at risk of
      frank endocrine disorders, rapid and correct diagnosis, and appropriate
      management are essential steps to minimize morbidity and mortality. Finally,
      increasing evidence from in vitro studies suggests that various hormones may
      influence HIV replication as well as the course of HIV disease and associated
      disorders. Future studies on the molecular mechanisms of hormones on HIV action
      and clinical studies on the effects of hormones as adjunctives to established
      forms of therapy may stimulate development of novel therapeutic strategies that
      will benefit HIV-infected patients.

PMID- 8862349
TI  - Polymyositis as a manifestation of chronic graft-versus-host disease.
AB  - A syndrome indistinguishable from idiopathic polymyositis occurred in 11 patients
      as a manifestation of chronic GVHD. All patients had elevation of creatine
      phosphokinase (CPK). Immunohistology demonstrated the effector cells in the
      muscle infiltrates as cytotoxic T cells, a finding similar to idiopathic
      polymyositis. Polymyositis is a rarely reported complication of chronic graft
      versus-host disease (GVHD) with only 8 cases described in the literature. We
      encountered this syndrome in a small but significant percentage of our patients
      with chronic GVHD. Polymyositis associated with chronic GVHD does not affect the
      overall prognosis for the patient. Moreover, polymyositis can be the only
      manifestation of chronic GVHD. Awareness of this complication is important
      because it can be confused with other causes of muscle weakness after bone marrow
      transplantation. Finally, prompt initiation of corticosteroid therapy results in
      a rapid improvement of the associated symptoms.

PMID- 8862350
TI  - Breast cancer susceptibility genes.

PMID- 8862351
TI  - Survival of women with node negative breast cancer in the Auckland region.
AB  - AIMS: To assess the effect of prognostic factors on overall survival from node
      negative breast cancer. METHODS: Information was collected on 1138 node negative
      breast cancer patients in the Auckland region, diagnosed between 1976 and 1985.
      Prognostic variables investigated included oestrogen (ER) and progesterone (PR)
      receptor status, tumour grade, tumour size, body mass index, lactation history
      and parity. The effects of these variables on overall survival were assessed
      separately in pre and postmenopausal groups. RESULTS: Over a median follow up
      time of 10.2 years, improved survival was seen in premenopausal women with PR+
      status (p = 0.0007), ER+ status (p = 0.03), positive lactational history (p =
      0.03) and low tumour grade (p = 0.04). In postmenopausal women, only ER+ status
      (p = 0.01) and PR+ status (p = 0.02) were associated with improved survival.
      Multivariate analysis suggested that positive PR status combined with tumour size
      provided the best prognostic discrimination in premenopausal women, whereas ER
      status was the dominant prognostic variable in postmenopausal patients.
      CONCLUSIONS: For premenopausal node negative women, progesterone receptor status,
      considered either alone, or together with tumour size, provides the best
      prognostic prediction of survival. By comparison, oestrogen receptor status is
      the most important predictor of overall survival in postmenopausal women.

PMID- 8862352
TI  - Successful implementation of laboratory budget holding by Pegasus Medical Group.
AB  - AIMS: To evaluate the effectiveness of budget holding by Pegasus Medical Group
      for laboratory services expenditure and reasons for the successes observed.
      METHODS: Two pilot groups and a nonpilot group of general practitioners were
      formed with the pilots receiving active feedback, educational programmes and test
      form redesign within the incentive of savings being retained by the group for
      improved primary care services. RESULTS: Overall savings of 22.7% were achieved
      within the budget over a 13 month period. There was a highly significant
      reduction in expenditure per member especially in the mean and standard deviation
      of cost per consultation indicating a marked narrowing of the variance in cost
      between members in the pilot groups compared with the nonpilot group. CONCLUSION:
      The study illustrates the effectiveness of a comprehensive strategy of education,
      active feedback and test form redesign and especially the importance of the
      incentive of retaining budgetary savings for service improvements. It also
      illustrates the importance of collaborative as compared with competitive
      strategies in achieving cost control and value for money gains in health
      services. However, more work is needed to establish the appropriateness of lower
      laboratory expenditure by linking test requests to diagnosis.

PMID- 8862353
TI  - Public knowledge and attitudes towards the use of alcohol and drinking
      guidelines.
AB  - AIMS: To investigate public knowledge and attitudes towards the use of alcohol
      with particular focus on drinking guidelines. METHOD: A telephone survey of 249
      people randomly selected from the toll free area of Christchurch. RESULTS: Three
      key findings were (1) not one respondent was able to quote drinking guidelines
      that included quantities of alcohol per occasion or quantities of alcohol per
      week; (2) the majority of the public (74%) thought drinking guidelines were not
      publicised well enough; and (3) young men (18-24 years) were significantly more
      likely to state incorrectly that greater than six standard drinks is a safe
      amount of alcohol to consume on social occasions. CONCLUSIONS: More active
      promotion of drinking guidelines via the electronic and popular print media
      should be considered. Young men require particular attention related to drinking
      no more than six standard drinks per occasion of drinking as part of this
      initiative. Other studies targeting groups such as the more transient, different
      ethnic groups especially Maori and Pacific Islanders, health professionals and
      people with alcohol problems would be of interest, as well as a repeat of this
      study following an interim period in which active promotion of drinking
      guidelines is undertaken.

PMID- 8862354
TI  - General practitioners' opinions of continence care training.
AB  - AIMS: To examine general practitioners' confidence in the diagnosis and
      management of urinary incontinence, to define their unmet continence training and
      educational needs, and to evaluate the current provision of continence care in
      general practice, including the role of practice nurses. METHODS: A pre-tested
      postal questionnaire was sent to 600 general practitioners throughout New Zealand
      to obtain information about their demography and training in incontinence
      management, their confidence in diagnosis and treatment, and their perceptions of
      met and unmet educational needs in continence care. They were also asked about
      current provision of continence promotion in their practice and their views on
      the role of practice nurses in caring for incontinent patients. Confidence data
      were recorded on five point scales and analysed using chi square tests. Cluster
      analysis was used to describe groups with different opinions on practice nurses'
      roles. RESULTS: The response rate from eligible contacts was 81.3%. Although most
      respondents provide continence care, only 2.6% offered special clinics for
      continence promotion. Fewer than half felt confident to diagnose the causes of
      incontinence. Confidence in managing incontinence in children was consistently
      lower than for other incontinence presentations. There was no difference by sex
      in confidence in caring for incontinent patients although female respondents were
      more likely to consider management of continence care part of a practice nurse's
      role (chi 2 = 47.5, p < 0.01) and to routinely ask well women about incontinence
      (chi 2 = 243.6, p < 0.01). Most respondents (71.9%) could not remember having had
      any formal training in the management of incontinence at either undergraduate or
      postgraduate level. Recall of postgraduate education was associated with greater
      levels of confidence in management of continence problems. There was general
      agreement that it was appropriate to include training in continence management in
      vocational and continuing medical education. CONCLUSION: A substantial proportion
      of general practitioners perceive a lack of adequate medical training in
      incontinence care at both undergraduate and postgraduate levels. There is a need
      for improved education for both general practitioners and practice nurses.

PMID- 8862355
TI  - Breastfeeding in Canterbury over three decades.
AB  - AIM: To document breastfeeding levels in Canterbury between 1968 to 1994.
      METHODS: The method of feeding at discharge from hospital, at 4 weeks and at 3
      months of age was obtained from maternal obstetric records, Plunket nursing
      notes, parent interviews or by self completed questionnaires. Data were compiled
      for the years 1968 to 1994. RESULTS: In 1968, only half of all mothers were
      breastfeeding when discharged. However, rates have steadily increased since then
      so that by 1990, 90% of infants were recorded as being breastfed at discharge.
      Levels of exclusive breastfeeding have also increased. By 1992-4, 82.2% of babies
      were being exclusively breastfed at discharge from hospital, 72.4% at 4 weeks and
      62.5% at 3 months. CONCLUSION: Levels of breastfeeding in Canterbury are now
      relatively high. The Public Health Commission has set a target for 75% of infants
      to be fully breastfed at 3 months of age by the year 2000. To achieve this the
      circumstances that hinder breastfeeding need to be addressed.

PMID- 8862356
TI  - NHF guidelines on the management of dyslipidaemia.

PMID- 8862357
TI  - Intracytoplasmic sperm injection.

PMID- 8862358
TI  - Interaction between miconazole oral gel (Daktarin) and warfarin.

PMID- 8862359
TI  - Out of hospital cardiac arrest.

PMID- 8862360
TI  - Referral for abortion.

PMID- 8862361
TI  - Hypokalaemia following bowel cleansing with sodium phosphate.

PMID- 8862362
TI  - Surgical education--addressing the challenges of change.

PMID- 8862363
TI  - Double adult renal allografts: a technique for expansion of the cadaveric kidney
      donor pool.
AB  - BACKGROUND: A major impediment to kidney transplantation is the current shortage
      of donor organs. Currently approximately 22,500 candidates are awaiting kidney
      transplantation, while the number of donors remains stable at approximately 3500
      each year in the United States. Alternative approaches to traditional organ donor
      selection are necessary. In this setting we hypothesized that kidneys with
      reduced nephron mass from adult donors may provide satisfactory renal function if
      both donor kidneys are placed into a single recipient. METHODS: Eighteen paired
      adult renal allografts were transplanted into nine adult recipients (DUAL).
      Recipient graft outcome variables were examined and compared with outcomes from
      single kidneys transplanted from randomly selected "ideal" donors younger than 50
      years of age (CONT < 50) and "expanded" donors older than 60 years of age (CONT >
      60) who underwent transplantation at our center. RESULTS: Six-month serum
      creatinine levels in the three groups, DUAL (n = 9), CONT < 50 (n = 20), and CONT
      > 60 (n = 12), were 1.6 +/- 0.3, 2.3 +/- 0.3, and 4.1 +/- 0.9 mg/dl,
      respectively, (p < 0.0001) between CONT > 60 and the other two groups. Mean
      estimated creatinine clearance (ml/min/1.73 m2) was 43.2 +/- 3.4, 62.5 +/- 5.4,
      and 24.5 +/- 5.3 (p < 0.02). Graft and patient survival at last follow-up in DUAL
      was 100% compared with 95% in CONT < 50 and 75% graft and 83% patient survival in
      CONT > 60. Delayed graft function occurred in one of nine patients (11%) in DUAL
      group compared with 4 of 20 (20%) in CONT < 50 group and 6 of 12 (50%) in CONT >
      60 group. Mean follow-up of patients in DUAL group was 6.6 months (range, 2 to 14
      months). CONCLUSIONS: Double adult kidney transplants (DUAL) are associated with
      acceptable short-term graft function, graft survival, and patient survival when
      compared with transplanted kidneys from an ideal donor group (CONT < 50). Double
      renal allografts are a preferred use for donor kidneys with suboptimal nephron
      mass. Long-term follow-up is required to validate further the proposed approach.

PMID- 8862364
TI  - Determinants of success of color-flow duplex-guided compression repair of femoral
      pseudoaneurysms.
AB  - BACKGROUND: Ultrasonography-guided compression repair is reported to be effective
      therapy for femoral pseudoaneurysms that develop after catheterization
      procedures. This study summarizes our experience with color-flow duplex-guided
      repair of these lesions. METHODS: A retrospective chart review of all patients
      who underwent this procedure was undertaken, with statistical analysis to
      identify factors associated with success. RESULTS: Compression repair of 69
      pseudoaneurysms was attempted. Pseudoaneurysms developed after therapeutic
      catheterization in 48 patients and after diagnostic procedures in 21. Sites of
      arterial puncture were the common femoral artery in 59 patients and the
      superficial femoral or profunda femoris arteries in 10. Diameters of the
      pseudoaneurysms ranged from 3 to 60 mm (mean, 28 mm). Compression was attempted
      at a mean of 5 days (range, 1 to 21 days) after catheterization. Compression
      produced complete thrombosis of the pseudoaneurysm at the initial attempt in 43
      (62%) of 69 patients. With repeated attempts the ultimate success was 47 (68%) of
      69. Success was achieved in 44 (75%) of 59 common femoral pseudoaneurysms but in
      only 3 (30%) of 10 superficial femoral or profunda femoris lesions (p = 0.009).
      Anticoagulation, sheath size, pseudoaneurysm chamber size, and time between
      catheterization and compression were not significantly different between lesions
      that were successfully compressed and those that were not. No ischemic or embolic
      complications were observed. CONCLUSIONS: Color-flow duplex-guided compression
      repair can be safely attempted as the initial therapy for all uncomplicated
      pseudoaneurysms arising from the common femoral artery after catheterization,
      with the expectation of success in most.

PMID- 8862365
TI  - Survival after repeat hepatic resection for recurrent colorectal hepatic
      metastases.
AB  - BACKGROUND: This is a retrospective clinical study done to examine survival of
      patients undergoing repeat hepatic resection for recurrent colorectal hepatic
      metastases. METHODS: The records of 131 patients undergoing hepatic resection for
      metastatic colorectal cancer were reviewed. Curative resection was performed in
      107 of these patients. Thirty-one experienced recurrences confined to the liver.
      Thirteen (13 of 107, 12%) of them underwent resection and make up the study
      population. RESULTS: The eight men (62%) and five women (38%) had a median age of
      60 years (range, 32 to 75 years). In 30% of patients recurrence developed near
      the original resection site. In 70% the recurrences were remote from the original
      site. The patients underwent a total of six wedge resections, two left lateral
      segmentectomies, three right lobectomies, and two trisegmentectomies. Average
      blood loss was 2995 cc; average hospital stay was 17.2 days. Morbidity was 23% (3
      of 13); mortality was 8% (1 of 13). Four patients died of recurrent disease, with
      a mean disease-free survival of 9.7 months (median, 7.5 months; range, 3 to 21
      months) and mean total survival of 39 months (median, 24 months; range, 8 to 99
      months). One of these patients had a second recurrence resected at month 21 and
      lived an additional 78 months. Seven patients were alive with no evidence of
      disease, with a mean follow-up time of 34.9 months (median, 14 months; range, 1
      to 186 months). Actual 5-year survival was 23% (3 of 13). Actual disease-free 5
      year survival was 15% (2 of 13). CONCLUSIONS: In properly selected patients
      morbidity, mortality, and survival after repeat resection are similar to those
      after initial resection.

PMID- 8862366
TI  - Dopexamine prevents depression of mesenteric blood flow caused by positive end
      expiratory pressure in rats.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of two
      vasoactive agents, dopamine and dopexamine, on the depression of mesenteric blood
      flow caused by positive end-expiratory pressure (PEEP) during mechanical
      ventilation. METHODS: Sprague-Dawley rats were mechanically ventilated with
      either no PEEP (control group) or increasing levels of PEEP (PEEP group) up to 20
      cm H2O pressure. We evaluated PEEP's effect on blood pressure, cardiac output
      (CO), and the mesenteric microcirculation with a continuous infusion of 2.5 or
      12.5 micrograms/kg/min dopamine or 1, 3, or 5 micrograms/kg/min dopexamine.
      RESULTS: PEEP caused a 20% to 25% decrease in mean arterial pressure and a 30%
      decrease in CO at both 15 and 20 cm H2O of PEEP (all p < 0.05 versus baseline).
      Low dose dopamine partially corrected the decrease in CO to 16% and 21% below
      baseline at 15 and 20 cm H2O of PEEP, respectively (both p < 0.05 versus PEEP
      group) and partially ameliorated the depression of mesenteric blood flow
      associated with the application of PEEP. High dose dopamine did not positively
      affect either CO or mesenteric blood flow. Dopexamine had little effect on CO
      compared with dopamine. All three doses of dopexamine blocked the effect of PEEP
      on mesenteric blood flow (p < 0.05 compared with the PEEP group at all levels of
      PEEP, p < 0.05 compared with the low dose dopamine group at 15 and 20 cm H2O of
      PEEP). CONCLUSIONS: Dopexamine is superior to dopamine in protecting mesenteric
      blood flow in the face of increasing levels of PEEP.

PMID- 8862367
TI  - Thoracoscopic splanchnicectomy for chronic pancreatitis pain.
AB  - BACKGROUND: The study was undertaken to quantitate the effects of thoracoscopic
      splanchnic nerve resection (SPL) on pain from chronic pancreatitis. METHODS:
      Patients with chronic pancreatitis pain completed an analog pain scale before
      operation and at postoperative visits. Midepigastric and left-sided pain was
      treated with left SPL; right-sided pain was treated with right-sided SPL. If pain
      recurred on the contralateral side, the patient underwent contralateral SPL.
      RESULTS: Fifteen patients underwent SPL. Eleven patients required daily narcotics
      for relief of pain before operation. Eight patients had unilateral SPL, whereas
      seven ultimately had a bilateral operation (median follow-up, 18 months).
      Fourteen patients had constant pain before operation, which decreased to a mean
      of 2.8 attacks per month (p < 0.0001). Before operation, the "worst pain within
      last two months" was 9.1 on pain scale (range, 0 for no pain, to 11 for constant
      pain). After operation this decreased to 5.1 (p < 0.002). "Current severity" of
      pain decreased from 6.5 before operation to 2.0 after operation (p < 0.0005). The
      "amount pain is interfering with daily activities" decreased from 7.3 before
      operation to 2.3 after operation (p < 0.0001). Seven patients (46%) no longer
      require narcotics and are classified as having had good results. Five patients
      (33%) are classified as improved and have had a major reduction in narcotic
      needs. Three have had no significant pain relief and are classified as having had
      poor results. CONCLUSIONS: Thoracoscopic SPL offers substantial promise in the
      therapy of pain from chronic pancreatitis.

PMID- 8862368
TI  - Cost analysis of early extubation after coronary bypass surgery.
AB  - BACKGROUND: Although early extubation after coronary bypass surgery has been
      shown to reduce length of stay, a systematic cost analysis of its economic
      benefit has not been reported, and previous studies have used hospital charges
      that are typically confused with actual costs. METHODS: A consecutive series of
      690 patients undergoing coronary bypass surgery during a 24-month period were
      studied to determine the effect of early extubation, defined as removal of the
      endotracheal tube within 8 hours of arrival to the intensive care unit, on length
      of stay and hospital costs. Patients in group 2 (n = 362) who underwent coronary
      bypass surgery in 1995, subsequent to the initiation of an early extubation
      protocol, were compared with those in group 1 (n = 328) operated on in 1994,
      before implementation of early extubation. To reflect true hospital resource
      consumption, only costs (not charges) directly related to patient health core
      (variable direct cost) were analyzed. RESULTS: Baseline characteristics such as
      age, gender, previous myocardial infarctions, ejection fraction, reoperations,
      diabetes, and left main stenosis were similar in both groups. Operative mortality
      for the entire group was 3.3% and did not differ between the two groups; the
      incidence of serious morbidity was 10.9% for the entire group. Early extubation
      was accomplished in 38% of patients in group 2 versus 3% in group 1 (p < 0.001),
      and postoperative length of stay declined from 9.4 days to 7.7 days (p < 0.01).
      This was accompanied by a significant (p = 0.001) reduction in variable direct
      cost per case. CONCLUSIONS: Early extubation after coronary bypass surgery is an
      effective strategy of reducing length of stay and does not appear to impact on
      either morbidity or mortality. An additional benefit is significant cost savings
      realized through accelerated recovery and control of resource use.

PMID- 8862369
TI  - Economics of pancreatoduodenectomy in the elderly.
AB  - BACKGROUND: Managed care and the increasing percentage of surgical procedures
      performed in the elderly have renewed the focus on hospital charges and
      expenditures. The objective of this study was to determine whether
      septuagenarians and octogenarians accrue more hospital charges or have a higher
      risk of morbidity and death. METHODS: We retrospectively reviewed the charges and
      pertinent clinical outcomes data that were available on 70 of the last 100
      pancreatoduodenectomies performed at our institution (1989 to 1994). Charges from
      four cost centers were analyzed and normalized to 1995 dollars by using the
      Consumer Price Index and Wilcoxon rank sum test. Patients were divided into two
      groups: group 1, 70 years of age or older (n = 21); group 2, younger than 70
      years of age (n = 49). RESULTS: Anesthetic charges were $2657 +/- $835 for group
      1 versus $2815 +/- $826 for group 2, which was not a statistically significant
      difference. Laboratory charges were $4650 +/- $3284 for group 1 versus $5969 +/-
      $5169 for group 2, which was not a significant difference. Pharmaceutical charges
      were $5424 +/- $4435 for group 1 versus $9243 +/- $9695 for group 2, which was
      not a significant difference. Charges for operative units were $6198 +/- $1671
      for group 1 versus $7469 +/- $2116 for group 2, p < 0.02. Total charges were
      $41,180 +/- $20,635 for group 1 versus $50,968 +/- $33,783 for group 2, which was
      not a significant difference. No difference was noted in morbidity, mortality,
      length of stay, or survival. CONCLUSIONS: Pancreatoduodenectomy in the elderly
      can be performed safely without accruing higher cost, increased morbidity, or
      increased mortality.

PMID- 8862370
TI  - Current management of visceral artery aneurysms.
AB  - BACKGROUND: Visceral artery aneurysms are an uncommon but important form of
      abdominal vascular disease. This study reviews a contemporary experience with
      special emphasis on newer methods of diagnosis and treatment. METHODS: From 1980
      to 1994, 37 patients were diagnosed with 46 visceral artery aneurysms. These
      consisted of 22 splenic, 10 hepatic, 4 superior mesenteric, 2 gastroduodenal, 3
      celiac, 2 left gastric, 1 pancreatoduodenal, 1 jejunal-ileal, and 1 inferior
      mesenteric artery aneurysms. Follow-up was complete for 28 patients, average of
      37.7 months. There were 17 asymptomatic and 29 symptomatic aneurysms, including
      11 presenting with rupture. RESULTS: Seventeen patients were treated surgically,
      with no surgical deaths. Surgical complications included splenic abscess (two)
      and failure to thrombose (one). Transcatheter embolization was used in 12
      patients. Complications included splenic infarction (one) and recurrence (two),
      successfully treated with repeat embolization. Nine patients were treated with
      observation. Eight experienced no complications during follow-up; one died of a
      ruptured splenic artery aneurysm before treatment was initiated. CONCLUSIONS: The
      widespread use of computed tomography has led to increased detection of
      asymptomatic visceral artery aneurysms. Although surgery remains necessary in
      many patients, transcatheter embolization is effective in the treatment of
      selected visceral artery aneurysms with few complications and low recurrence.

PMID- 8862371
TI  - Eversion endarterectomy of the internal carotid artery: technique and results in
      449 procedures.
AB  - BACKGROUND: Preservation of neurological function with a low incidence of
      restenosis is a measure of the long-term durability of carotid endarterectomy.
      Routine and selective patch angioplasty of the internal carotid artery have both
      been used to reduce the incidence of restenosis. The European literature has had
      many reports of lower restenosis rates in patients undergoing eversion carotid
      endarterectomy. We evaluated our experience with the eversion carotid
      endarterectomy procedure over a 2-year period to identify any advantage of this
      technique. METHODS: Between August 1993 and August 1995, 376 patients underwent
      449 carotid endarterectomies (CEAs) using the eversion technique (described
      below). During the same period, 307 patients underwent 353 CEAs by standard
      endarterectomy. Demographics were similar in both groups. Fifty-two patients in
      the eversion group underwent combined open cardiac procedures and carotid
      endarterectomy. There were 47 such patients in the standard group. Duplex
      examination was performed after surgery at regular intervals to identify any
      recurrent stenosis. RESULTS: Operative mortality was 4 of 376 (1.1%) and 6 of 307
      (2%) in the eversion and standard groups, respectively. Shunts were used in 15 of
      449 patients in the eversion group and 24 of 353 patients in the standard group.
      Cervical block anesthesia was used in 669 of 687 (97%) of patients undergoing CEA
      without coronary artery bypass grafting (CABG). There were four permanent
      neurologic deficits in the eversion group and seven in the standard group, for
      respective stroke rates of 0.9% and 2%, and there were three transient neurologic
      deficits in the eversion group and nine in the standard group. There was one
      (0.2%) restenosis in the eversion group; there were four (1.1%) in the standard
      group by follow-up duplex scan. CONCLUSIONS: These data demonstrate that eversion
      carotid endarterectomy can be performed with low stroke and mortality rates in
      the treatment of extracranial carotid occlusive disease. The incidence of
      restenosis was lower and approached significance in eversion endarterectomy when
      compared to standard carotid endarterectomy in the short-term follow-up in this
      series.

PMID- 8862372
TI  - Transabdominal esophagogastric devascularization as treatment for variceal
      hemorrhage.
AB  - BACKGROUND: During the past 18 years we have used a selective operative approach
      for variceal bleeders in whom endoscopic sclerotherapy failed or sclerotherapy
      was not indicated. Esophagogastric devascularization with splenectomy has been
      reserved for unshuntable patients and for those in whom a shunt was deemed
      inadvisable. The purposes of this study are to describe the surgical procedure
      technique and indications for esophagogastric devascularization and to report its
      long-term results. METHODS: Thirty-two patients who underwent either a limited (n
      = 9) or extensive (n = 23) esophagogastric devascularization procedure without
      esophageal transection for variceal bleeding were retrospectively reviewed.
      Common indications were thrombosis of all splanchnic veins (n = 12), distal
      splenorenal shunt thrombosis (n = 7), generalized portal hypertension with
      isolated splenic vein thrombosis (n = 5), and symptomatic splenomegaly or severe
      hypersplenism (n = 6). Eighteen patients (56%) had cirrhosis, eleven (34%)
      received an emergency operation, and eighteen (56%) bled from gastric varices.
      RESULTS: Three patients with Child's class C disease undergoing emergency surgery
      died during the early postoperative interval. Rebleeding occurred in nine
      surviving patients (31%) and was the cause of death in three. Rebleeding rates
      for the limited and extensive devascularization procedures were 50% and 24%,
      respectively. Only one of 11 patients with diffuse splanchnic venous thrombosis
      without liver disease has died. The 5-year survival rate of patients with liver
      disease was 51%. Only two patients experienced postoperative encephalopathy.
      CONCLUSIONS: When used in selected patients, esophagogastric devascularization
      without esophageal transection is a reasonably effective alternative to shunt
      surgery.

PMID- 8862373
TI  - Gastrointestinal perforation and peritonitis in infants and children: experience
      with 179 cases over ten years.
AB  - BACKGROUND: Premature infants continue to have a high mortality after
      gastrointestinal perforation. This report describes 179 patients with
      gastrointestinal perforation and peritonitis and compares etiologic factors,
      mortality, and causes of death in premature infants and older children in an
      attempt to predict outcome. METHODS: The 113 boys (63.1%) and 66 girls (36.9%)
      had an age range of newborn (n = 139, 77.6%) to 17 years. Site of perforation was
      gastric in 16, duodenal in 9, small bowel in 105, colon in 37, and undesignated
      in 12. Eighteen had multiple perforations. Etiologic factors in newborns (younger
      than 2 months) included necrotizing enterocolitis (NEC) (75, 41.9%), isolated
      ileal perforations (30, 21.5%), malrotation/volvulus (8), iatrogenic causes (5),
      and others (6). Gestational age was 29.6 +/- 4.3 weeks for NEC versus 31.4 +/-
      5.4 weeks for non-NEC. Birth weight for patients with NEC was 1.45 +/- 0.8 gm and
      1.81 +/- 1.0 gm for non-NEC babies. Etiologic factors in 33 older children (older
      than 2 months to 17 years) were trauma (10), Meckel's diverticulum (4),
      intussusception (2), pseudomembranous colitis (2), adhesions (2), stomal leak
      (2), others (4), and nondesignated (7). Gastric perforations (n = 16) were
      iatrogenic in 7, idiopathic in 5, and caused by an ulcer in 4. RESULTS: Mortality
      for NEC was 36 of 75 (48%), 15 of 55 (27.2%) for non-NEC infants (p < 0.05 versus
      NEC), 15.1% (5 of 33) for older children (p < 0.05 versus NEC), and 4 of 16 (25%)
      for gastric perforation. Infant deaths were related to overwhelming sepsis,
      immaturity of systems, and multiorgan failure. Deaths for older children were a
      result of sepsis, multiorgan failure, and immunodeficiency. CONCLUSIONS:
      Gastrointestinal perforation is more common in premature infants with the highest
      mortality (48%) noted in NEC. Despite surgical intervention and advances in
      neonatal intensive care unit care, premature low birth weight infants (especially
      NEC) continue to have a high mortality.

PMID- 8862374
TI  - Free radical scavenging by lazaroids improves renal blood flow during sepsis.
AB  - BACKGROUND: Acute kidney failure in surgical patients is often related to severe
      infection. Renal vasoconstriction is a major factor in the genesis of kidney
      failure. Reactive oxygen species (ROS) are known to mediate kidney injury after
      ischemia-reperfusion and are increased during sepsis. The role of ROS as
      mediators of intrarenal vasoconstriction and renal dysfunction during sepsis is
      unclear. Lazaroids such as U74389G are radical quenching antioxidants that
      inhibit ROS-induced lipid peroxidation. We sought to determine whether radical
      scavenging affected the renal microvascular response to a septic challenge.
      METHODS: In vivo videomicroscopy was used to study the rat hydronephrotic kidney.
      Interlobular artery (ILA) diameter and flow, afferent and efferent arteriolar
      diameters, and cardiac output were measured. U74389G or vehicle was infused
      before a bolus injection of live Escherichia coli or normal saline solution.
      RESULTS: U74389G alone had no effect on the renal vessels or hemodynamics. E.
      coli caused preglomerular vasoconstriction (ILA, -32%; afferent, -30% of
      baseline) and hypoperfusion (-66%) despite increased cardiac output (+54%).
      U74389G significantly attenuated both the constriction (ILA, -16%; afferent, -9%)
      and hypoperfusion (-38%) but not increased cardiac output (+41%). CONCLUSIONS: E.
      coli bacteremia led to preglomerular vasoconstriction and hypoperfusion.
      Inhibition of lipid peroxidation with the radical scavenger U74389G reduced this
      effect without altering central hemodynamic responses. Free radicals have a
      deleterious effect on the renal microcirculation during bacteremia, and these
      data suggest that antioxidants may be of value in preventing sepsis-associated
      kidney failure.

PMID- 8862375
TI  - Adverse effect of donor vasopressor support on immediate and one-year kidney
      allograft function.
AB  - BACKGROUND: This purpose of this study was to determine if there was a
      significant difference between the rates of acute tubular necrosis (ATN) and long
      term graft survival in renal allografts procured from donors requiring inotropic
      support (DRIS) and those from donors not requiring inotropic support. METHODS:
      Eighty-two consecutive cadaveric renal transplant patients were prospectively
      followed in our local procurement area, the Delaware Valley Transplant Program.
      Forty-eight patients received organs from DRIS (> 10 mcg/kg per minute of
      dopamine, dobutamine, epinephrine, and norepinephrine alone or in combination),
      and 34 did not. RESULTS: Allografts from the non-DRIS group had an immediate
      function rate of 82.4% and a 1-year function rate of 91.2%. In comparison, the
      DRIS grafts had an immediate function rate of 58.3% and a 1-year function rate of
      72.9%. These differences were statistically significant. The mean serum
      creatinine in the non-DRIS group was 1.46 +/- 0.58 mg/dl, whereas in the DRIS
      cohort it was 1.89 +/- 0.93 mg/dl. CONCLUSIONS: Kidneys transplanted from DRIS
      had significantly (1) poorer immediate function, (2) worse 1-year survival rates,
      and (3) higher serum creatinine at 1 year. We conclude that recipients receiving
      organs from donors requiring inotropic support are at a higher risk of developing
      ATN after surgery and experience reduced 1-year function.

PMID- 8862376
TI  - Operative strategies for management of abdominal aortic gunshot wounds.
AB  - BACKGROUND: Although management of penetrating abdominal trauma has greatly
      improved, abdominal aortic gunshot wounds (AAGSWs) remain a highly lethal injury.
      Our experience with AAGSWs was reviewed to define operative strategies that may
      improve survival. METHODS: Forty-one patients with AAGSWs were treated between
      1976 and 1996. Preliminary thoractomy was performed in seven patients. Thirty
      nine patients had at least one major associated injury (average, 3.2). RESULTS:
      Twenty-one patients died. Six of seven patients who underwent preliminary
      thoracotomy died; all developed coagulopathy, which appeared to contribute to
      death. Four patients had missed vascular lesions, two of which contributed to
      their death. Associated injuries are currently managed by "damage control"
      strategy, in which some injuries are left untreated to focus on hemorrhage
      control. CONCLUSIONS: We have identified seven operative principles and
      procedures that we believe may improve survival: (1) thorough knowledge of
      supraceliac exposure; (2) rapid aortic control at the hiatus rather than by a
      preliminary thoracotomy; (3) use damage control or abbreviated laparotomy; (4)
      use packing and mesh closure when coagulopathy and hypothermia are present; (5)
      primary concern should be cessation of hemorrhage rather than the maintenance of
      flow; (6) delayed reconstruction using extraanatomic bypass can restore flow; and
      (7) use angiography to detect missed vascular lesions or problems with vascular
      repair.

PMID- 8862377
TI  - Impact of cholesterol reduction on peripheral arterial disease in the Program on
      the Surgical Control of the Hyperlipidemias (POSCH).
AB  - BACKGROUND: Few lipid/atherosclerosis intervention trials have assessed the
      impact of cholesterol reduction on peripheral arterial disease. The 838 patients
      evaluated in the Program on the Surgical Control of the Hyperlipidemias (POSCH)
      trial represent more than the total number of patients in the seven previously
      reported studies. METHODS: Peripheral arterial disease in POSCH was assessed by
      progression of clinical disease, serial changes in the systolic blood pressure
      ankle/brachial index (ABI), and changes on sequential peripheral arteriograms.
      RESULTS: At the time of formal closure of the POSCH trial on July 19, 1990,
      claudication or limb-threatening ischemia was exhibited in 72 of 417 control
      group (CG) patients and in 54 of 421 intervention group (IG) patients (IG
      relative risk [RR] 0.702, 95% confidence interval [CI] 0.169 to 1.000, p =
      0.049). With additional follow-up evaluation to September 30, 1994, clinical
      peripheral arterial disease was evident in 91 CG patients and 64 IG patients (RR
      0.656, 95% CI 0.200 to 0.903, p = 0.009). At the 5-year follow-up evaluation, an
      ABI of less than 0.95 was present in 41 of 120 CG patients and in 24 of 126 IG
      patients, all of whom had an ABI of 0.95 or greater at baseline (RR in the IG of
      0.557, 95% CI 0.360 to 0.863, p < 0.01). No appreciable differences were noted in
      the progression or regression of arteriographic peripheral arterial disease
      between the two groups. CONCLUSIONS: Effective cholesterol reduction in POSCH led
      to statistically significant differences between the control and the intervention
      groups in the development of clinically evident peripheral arterial disease and
      in the ABI values, but not in the peripheral arteriograms. Additional studies
      need to assess the correlation between peripheral arterial changes and coronary
      arterial changes and clinical atherosclerosis events. Intervention trials that
      study peripheral arterial disease have intrinsic value in the evaluation of the
      impact of risk factor modification on progression of atherosclerotic peripheral
      arterial disease.

PMID- 8862378
TI  - Population-based analysis of treatment of pancreatic cancer and Whipple
      resection: Department of Defense hospitals, 1989-1994.
AB  - BACKGROUND: The influence of hospital experience and referral patterns on the
      operative mortality rate of pancreaticoduodenectomy was studied in a worldwide
      hospital system. METHODS: We analyzed computerized data on pancreatic cancer
      patients from U.S. Department of Defense (DOD) hospitals from 1989 to 1994.
      RESULTS: Six hundred ninety-eight patients had pancreatic cancer, and 130 Whipple
      operations (105 for pancreatic and 25 for other cancers) were performed with an
      8.5% 30-day operative mortality rate. Although most resections were done in
      teaching hospitals performing more than 1 Whipple procedure per year, their
      results were not superior to smaller, lower volume nonteaching hospitals.
      Patients transported for resection were younger than patients undergoing
      resection at their local DOD hospital but had similar outcomes. The operative
      mortality rate was higher after unusual resections and with increasing age; the
      tumor stage had no effect. Unresected patients undergoing combined radiation and
      chemotherapy had the longest survival times. Radiation therapy was associated
      with significantly longer survival times in patients without distant metastases,
      but chemotherapy was associated with a longer survival time when metastases were
      present. CONCLUSIONS: This mortality rate 8.5% for Whipple resections matches
      that from other large populations. Equivalent results were obtained in DOD
      teaching hospitals and smaller, community-type institutions. Because the DOD
      medical system minimizes financial and logistic barriers to transfer, the even
      distribution of DOD pancreatectomy mortality suggests that these barriers may
      favorably influence single institutional outcomes.

PMID- 8862379
TI  - Thoracic versus lumbar epidural anesthesia's effect on pain control and ileus
      resolution after restorative proctocolectomy.
AB  - BACKGROUND: Epidural anesthesia as a perioperative adjunct has been shown to
      provide superior pain control and has been implicated in more rapid ileus
      resolution after major abdominal surgery, possibly through a sympatholytic
      mechanism. Studies suggest that the vertebral level of epidural administration
      influences these parameters. METHODS: One hundred seventy-nine patients (120
      male, 59 female; average age, 36 years) underwent restorative proctocolectomy for
      ulcerative colitis or familial polyposis between 1989 and 1995. Patients were
      grouped according to type of anesthesia. Group THO (n = 53) received thoracic (T6
      to T10) epidurals. Group LUM (n = 51) received lumbar (L2 to L4) epidurals, and
      group PCA (n = 75) received patient-controlled intravenous narcotic analgesia.
      Patients were compared for complications, perioperative risk factors,
      postoperative pain, and ileus resolution. RESULTS: Epidural narcotics, alone or
      combined with local anesthetics, were administered for an average of 2 (LUM) to 4
      (THO) days without significant complications. Infrequent problems related to the
      epidural catheters included self-limited headaches or back pain (four) and site
      infections (two). Epidural failure, as measured by conversion to PCA for
      inadequate pain control, was not significantly greater for LUM (25%) than THO
      (23%). Average pain scores, rated daily on a visual analog scale, were
      significantly higher (indicating more pain) for PCA patients (4.2) during
      postoperative days 1 through 5 than for LUM (3.5) (p < 0.05) and for THO (2.4) (p
      < 0.05). Ileus resolution, as determined by stool output and return of bowel
      sounds, was significantly faster in THO than in LUM or PCA (p < 0.05). Resolution
      of ileus was not significantly different between PCA and LUM (p > 0.05).
      CONCLUSIONS: Thoracic epidural analgesia has distinct advantages over both lumbar
      epidural or traditional patient-controlled analgesia in shortening parameters
      measuring postoperative ileus and in reducing surgical pain. The procedure is
      safe and associated with low morbidity. Thoracic epidural anesthesia is also
      economically justifiable and may prove to impact significantly on future
      postoperative management by reducing length of hospitalization. Our data and
      those of others are most striking in these regards for patients with thoracic
      catheters, indicating the importance of vertebral level in epidural drug
      administration.

PMID- 8862380
TI  - Primary liver transplantation without transfusion of red blood cells.
AB  - BACKGROUND: This study examines factors associated with the performance of
      orthotopic liver transplantation (OLT) without red blood cell (RBC) transfusion.
      METHODS: Between January 1992 and December 1994, 306 primary OLTs were performed
      with recipients divided into two groups: group 1 patients (61 recipients, 20% of
      total) underwent transplantation without packed RBCs, and group 2 patients (245
      recipients, 80% of cases) received a transfusion of at least 1 unit of RBCs
      during operation. RESULTS: Recipients in group 1 compared with group 2 had less
      advanced liver disease (20% hospitalized and 48% Child's class C versus 58%
      hospitalized and 73% Child's class C, p < 0.01) and lower frequency of right
      upper quadrant surgery (13% versus 25%, p < 0.05). Group 1 recipients also had
      significantly higher preoperative hematocrits (38% versus 33%, p < 0.01), lower
      prothrombin times (15.4 versus 16.7 seconds, p < 0.001) and partial
      thromboplastin times (36.9 versus 42.2 seconds, p < 0.01), a greater proportion
      of patients transplanted by piggyback technique (87% versus 59%, p < 0.001), and
      shorter operative times (7.9 hours versus 9.2 hours, p < 0.001). Moreover, a
      greater percentage of patients underwent OLT without RBC transfusion in each
      successive year: 9% in 1992, 21% in 1993, and 31% in 1994 (p < 0.001). Logistic
      regression analysis showed the following factors to be independent predictors of
      OLT without RBC transfusion. Preoperative Hct, United Network of Organ Sharing
      status, piggyback technique, operative time, and year of transplantation.
      CONCLUSIONS: OLT can be performed without transfusion of RBCs in recipients with
      less advanced liver disease, and surgical technique, along with increased
      experience by the transplant team, are important factors.

PMID- 8862381
TI  - Adrenalectomy in the era of laparoscopy.
AB  - BACKGROUND: Recently laparoscopy has been described as an alternative approach
      for performing adrenalectomy. This study attempts to define the frequency and
      indications for the various approaches to adrenalectomy including laparoscopy.
      METHODS: From October 1992 to December 1995, 43 adrenal glands were excised from
      40 patients, of whom 23 were women and 17 were men. Their ages ranged from 16 to
      71 years. Nineteen operations were performed for pheochromocytoma, 10 for
      cortical adenoma (CAd), 6 for aldosteronoma, 4 for adrenocortical cancer (ACC), 1
      for Cushing's disease (CD), and 1 for hemorrhagic cyst. Adrenalectomy was
      accomplished via a laparoscopic operation in 20 patients (8 CAds, 6
      pheochromocytomas, 5 aldosteronomas, and 1 HC) and via an open operation in 19
      patients (11 pheochromocytomas, 4 ACCs, 2 CAds, 1 CD, and 1 aldosteronoma). One
      patient with bilateral pheochromocytoma had an open and a laparoscopic
      adrenalectomy. RESULTS: Open operations included 15 transabdominal, 4 posterior,
      and 3 thoracoabdominal approaches for 22 glands. Laparoscopic operations included
      17 transabdominal and 4 retroperitoneal approaches for 21 glands. Reasons for
      open operations included obesity (1), patient choice (2), failed laparoscopy (2),
      previous abdominal surgery (3), extraadrenal location (5); and gland size greater
      than 8 cm (9). Of these cases, the two patient choices, the two failed
      laparoscopies, and two of the three previous abdominal operations were
      appropriate for laparoscopy. Each of the posterior approaches could have been
      done laparoscopically. CONCLUSIONS: More than 60% of surgically treatable adrenal
      disease may be approached laparoscopically. Transabdominal, and on occasion,
      thoracoabdominal approaches are indicated for larger adrenal lesions. Surgeons
      operating on the adrenal gland should be familiar with each of these various
      approaches for adrenalectomy.

PMID- 8862382
TI  - Introduction of human adenomatous polyposis coli gene into Min mice via cationic
      liposomes.
AB  - BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor-suppressor gene
      involved in familial polyposis coli (FAP), a hereditary disease heralded by the
      development of hundreds of colorectal adenomas. A mouse model for FAP, the
      multiple intestinal neoplasia (Min) mouse, develops multiple adenomatous polyps
      of the large and small intestine similar to their human counterparts. To test the
      feasibility of introducing normal human APC as a means of either preventing or
      reversing polyp formation, we describe a method of in vivo transfection of APC
      into colonic epithelium of the Min mouse. METHODS: Anesthetized young (4 weeks)
      Min mice were treated with enemas containing lipofectant and a normal human APC
      cDNA plasmid every 72 hours for 2 months and then euthanized at 24, 48, and 72
      hours after the last treatment. Polymerase chain reaction (PCR) was used to
      detect the presence of the plasmid DNA. RESULTS: PCR on the extracted colonic
      epithelial DNA showed the presence of plasmid DNA up to 72 hours after the last
      treatment. Expression of the plasmid construct was confirmed by reverse
      transcriptase-PCR. CONCLUSIONS: We have demonstrated the repeated introduction
      and detection of normal human APC in the colonic epithelium of the Min Mouse in
      vivo during an extended period of time with no toxic side effects by means of our
      prolonged therapy.

PMID- 8862383
TI  - Impact of improving immunosuppressive treatment on outcome in cadaveric kidney
      transplantation.
AB  - BACKGROUND: Since the advent of cyclosporine-based immunosuppression for
      cadaveric kidney transplants in 1983, several changes have been made in
      immunosuppressive management at the University of Wisconsin. Since 1986, OKT3 has
      been available to treat steroid-resistant rejection; since 1992, OKT3 has been
      used as an induction agent replacing antilymphocyte globulin; and since 1993,
      mycophenolate mofetil has been used in 104 patients. METHODS: The impact of
      different immunosuppressive strategies on overall and immunologic graft survival
      (defined as graft loss caused by rejection) was evaluated in 1210 primary
      cadaveric renal transplants at the University of Wisconsin. Covariables,
      including degree of human leukocyte antigen matching, age, gender, cause of
      kidney failure, and early graft dysfunction, were evaluated. The series was
      subdivided into four eras according to immunosuppressive regimen, and the results
      were analyzed by era. RESULTS: Our principal findings are that immunologic graft
      survival has improved significantly during this series whereas overall graft
      survival has not. Mycophenolate was associated with a significant decrease in
      acute rejection. For a given patient, graft loss from rejection becomes less
      likely over time. Late rejection poses a greater risk than early rejection for
      graft loss. CONCLUSIONS: Improving outcomes may be related to improving
      immunosuppressive treatment, increasing degree of human leukocyte antigen
      matching, and better early graft function.

PMID- 8862384
TI  - Appropriate indications for venous duplex ultrasonographic examinations.
AB  - BACKGROUND: Because of the rapid growth in requests for lower extremity venous
      duplex ultrasonographic examinations, we have evaluated test results to determine
      the appropriate indications for testing and whether there is overuse of this
      technique. METHODS: We reviewed the records of all patients who had duplex
      ultrasonogram during an 18-month period to rule out deep vein thrombosis (DVT).
      Test outcome was evaluated with data on the age, gender, outpatient or inpatient
      status, duration of symptoms, physical findings, and risk factors of the
      patients. RESULTS: We reviewed 3474 examinations; 1265 outpatients and 1231
      inpatients were evaluated to rule out DVT, and 978 patients were evaluated to
      rule out a source of pulmonary embolism. More outpatients were female, and they
      tended to be younger; outpatients also had more acute femoropopliteal DVT. The
      presence of sudden onset of unilateral swelling was a strong predictor of acute
      DVT in all three groups: 52% of such patients were found to have DVT. Mild
      unilateral symptoms with a coexistent risk factor was associated with a 10% to
      20% prevalence of acute DVT. Chronic unilateral swelling was associated with
      acute DVT only with a coexistent risk factor and only in 1% of such patients.
      Bilateral swelling was only associated with acute DVT in the inpatient
      population, with 17% of studies having positive results. If calf tenderness was
      the only symptom with no associated risk factors, seven (1.6%) of 415 patients
      had acute DVT and six of these were tibioperoneal. No patients with cellulitis or
      isolated joint pain had acute DVT. With clinically suspected pulmonary embolism
      in patients without associated symptoms or risk factors, 7 (1.5%) of 447 studies
      showed tibioperoneal disease with no acute femoropopliteal disease. CONCLUSIONS:
      The physical examination and clinical history of the patient remain important
      indicators of the presence (or absence) of lower extremity DVT and can guide the
      appropriate use of duplex ultrasonography for the diagnosis.

PMID- 8862385
TI  - Revascularization of the solitary kidney: a challenging problem in a high risk
      population.
AB  - BACKGROUND: Patients with significant atherosclerotic stenosis involving the
      artery to a solitary functioning kidney present a clinical challenge. METHODS:
      From August 1987 through August 1995, 35 of these patients (average age, 68.4 +/-
      6.9 years) were treated. Comorbid conditions included previous myocardial
      infarction in 23% of the patients, congestive heart failure (CHF) in 34%, chronic
      obstructive pulmonary disease in 20%, and diabetes in 20%. The average creatinine
      level of the patients was 2.5 +/- 1.5 mg/dl. Indications for revascularization
      were hypertension in 86%, hypertensive crisis with CHF in 17%, and renal
      insufficiency in 69%. Procedures performed included 19 extra-anatomic bypasses, 8
      concomitant with infrarenal aortic reconstruction and 2 concomitant with
      thoracoabdominal aortic aneurysm repair; 1 visceral segment endarterectomy; 1
      renal artery endarterectomy with reimplantation; I superior mesenteric to renal
      artery bypass; 1 aortorenal bypass; and 2 percutaneous angioplasties with staged
      nephrectomies. RESULTS: At discharge, 91% of patients had stable or improved
      renal function with an average creatinine level of 1.7 +/- 0.8 mg/dl.
      Hypertension was cured or improved in 85%. Perioperative mortality was 6%, and
      major morbidity was 43%, including the need for permanent (9%) and temporary (9%)
      dialysis, respiratory insufficiency (18%), two early reoperations, six cardiac
      complications, one case of gastrointestinal bleeding, and one stroke. In the
      follow-up period (mean duration, 39.2 months), survival has been 73%, and no
      additional patients have required dialysis. CONCLUSIONS: Although significant
      perioperative morbidity exists in this high risk population, the long-term
      preservation of renal function and improvement in hypertension make solitary
      renal revascularization worthwhile.

PMID- 8862386
TI  - Repair of complex giant or recurrent ventral hernias by using tension-free
      intraparietal prosthetic mesh (Stoppa technique): lessons learned from our
      initial experience (fifty patients).
AB  - BACKGROUND: Giant complex ventral hernias are difficult to repair, and recurrent
      rates are high (greater than 10%). Our aim was to review our experience with a
      modified Stoppa technique. METHODS: From 1991 to 1995, 50 patients underwent
      repair with a large panel of prosthetic mesh placed intraparietally posterior to
      rectus muscle but anterior to posterior rectus sheath; 27 had undergone one to
      five previous hernia repairs, and 14 patients had a simultaneous intraabdominal
      procedure. Mean follow-up (100%) has been 24 months. RESULTS: No operative deaths
      occurred. Hospital morbidity included four wound infections, 2 of which were
      serious and required mesh removal; both occurred in patients in whom the gut was
      opened for other simultaneous intraabdominal procedures. Late morbidity included
      two delayed wound infections/limited mesh infections managed by office
      debridement and open packing, three seromas, and transient abdominal wall pain in
      seven patients. Long-term follow-up showed no recurrent hernias in the 48
      patients without early serious mesh infections requiring mesh removal; thus the
      long-term success rate was 96% (48 of 50 patients). CONCLUSIONS: Recurrent rates
      after this modified Stoppa repair of giant complex giant ventral hernias are very
      low. Early or late mesh infection occurred in four patients. Tension-free
      prosthetic mesh repair offers a marked improvement in outcome. Because of the
      possibility of mesh infection, simultaneous, contaminated, or even clean
      contaminated intraperitoneal procedures should be avoided if possible.

PMID- 8862387
TI  - Nonoperative management of the ruptured spleen: a revalidation of criteria.
AB  - BACKGROUND: Our goal was to revalidate this institution's original criteria for
      safe nonoperative management of splenic injury. METHODS: This was a prospective
      series between October 1991 and December 1995 entering all patients with splenic
      injury to a modified algorithm. Patients were taken to the operating room if
      hemodynamically unstable (systolic blood pressure less than 90 mm Hg; pulse
      greater than 110 beats per minute) after 2 liters of fluid resuscitation,
      positive abdominal examination findings, American Association for the Surgery of
      Trauma Organ Injury Scale Grade IV or V injuries by computed tomographic scan
      (unless younger than 15 years old), or associated severe head injuries (unless
      younger than 15 years old), or age greater than 55. The remainder of the patients
      were closely observed. RESULTS: One hundred seventy-three patients were entered
      six were excluded by death before operating room salvage, and one was excluded
      because of operation for a ruptured thoracic aorta. Therefore 166 patients were
      reviewed. Seventy splenectomies and 18 splenorrhaphies were performed, and 78
      patients were treated nonoperatively (58% splenic salvage). Two failures occurred
      in the nonoperative group: a 16-year-old with a grade IV hilar injury was
      operated on on the eighth day after injury because of a continually falling
      hematocrit, and a 25-year-old with unresolved tachycardia was operated on at 6
      hours (97% success rate). The patients in the operative group had a greater
      severity of injury as determined by mean Injury Severity Score of 32, 18 deaths,
      a mean transfusion requirement of 14 units of blood compared with mean injury
      severity score of 21, two deaths from brain injury, and no transfusions given in
      58 of the 78 nonoperative cases. CONCLUSIONS: Prospectively applied, these
      guidelines allow the safe nonoperative management of patients with blunt splenic
      injury.

PMID- 8862388
TI  - Efficacy of blood cultures in the critically ill surgical patient.
AB  - BACKGROUND: Blood cultures are commonly obtained to delineate an infectious
      process in the ill surgical patient with fever, leukocytosis, or other septic
      parameters. We studied how often bacteremia was diagnosed, whether a positive
      blood culture changed therapy, and the cost analysis of this practice. METHODS: A
      heterogenous adult population of 158 patients at high risk for bacteremia was
      retrospectively reviewed. Blood cultures were not obtained in 37 patients, and
      thus they were excluded from further study. RESULTS: We obtained 1040 blood
      cultures in 121 patients. Forty-eight patients (40%) had 122 positive cultures;
      20 of these patients had only false-positive cultures. Thus 28 patients (23%) had
      82 cultures that represented true bacteremia. Among clinical events, only
      antibiotic changes and interventions occurred significantly more often as a
      result of a positive blood culture (p < or = 0.05). No change in therapy occurred
      in most patients with both positive and negative cultures. Cost for all cultures
      was $60,058 or $1,251 per positive culture and $1,877 per clinical therapeutic
      event change. CONCLUSIONS: Routine ordering of blood cultures is not cost
      effective, rarely alters or provides therapeutic direction, and appears not to
      affect mortality. Obtaining clinically indicated blood cultures as a secondary
      rather than a primary diagnostic measure is suggested.

PMID- 8862389
TI  - Gallbladder and biliary tract candidiasis.
AB  - BACKGROUND: The clinical significance of Candida spp isolated from the
      gallbladder on the biliary tract is relatively unknown. METHODS: To provide this
      information, patients with Candida spp isolated from gallbladder and other
      biliary tract sources during a 10-year period were identified through the records
      of our clinical microbiology laboratory. Medical records were analyzed for
      biliary disease causes, culture data, treatment, and outcome. RESULTS: Twenty
      seven patients were identified. Five of seven patients with cholecystitis were
      critically ill intensive care unit (ICU) patients in whom the mortality rate was
      100%. Gallstone pancreatitis was found in four patients and was fatal in one
      patient with a pancreatic abscess and ongoing retroperitoneal sepsis. An external
      biliary shunt/endoprosthesis was placed in 16 patients to relieve biliary
      obstruction. Cholangitis was present in 14 patients, and most bile cultures
      contained Candida as part of a mixed flora. Only 3 of 27 patients had candidemia,
      and 22 of 27 patients were colonized with Candida at other sites. CONCLUSIONS:
      (1) The ICU patient with Candida cholecystitis has a grave prognosis. (2)
      Patients with Candida isolated from biliary stents placed for obstruction and
      cholangitis should be treated with both antifungal and broad spectrum
      antimicrobial agents. (3) Candidemia is not frequently seen in this setting.

PMID- 8862390
TI  - Effect of very delayed repair of congenital diaphragmatic hernia on survival and
      extracorporeal life support use.
AB  - BACKGROUND: Since November 1992, operative repair in neonates with congenital
      diaphragmatic hernia (CDH) at this institution was delayed until respiratory
      insufficiency had resolved. METHODS: A retrospective analysis was performed (n =
      33) comparing delayed repair with our previously reported institutional
      experience with immediate repair from January 1988 to October 1992 (n = 66).
      Infants with severe genetic defects or moribund conditions or who were premature
      were not considered candidates for repair or extracorporeal life support (ECLS),
      but they were included in the survival analysis. Survival was defined as hospital
      discharge. Data were compared with an independent t test or Pearson chi-squared
      test. RESULTS: Mean age at repair was 8.9 +/- 4.5 days (range, 3 to 20 days).
      Eleven infants in the study group were placed on ECLS (33% versus 68% in the
      comparison group; p = 0.001). Six of these infants survived (55% versus 58% in
      the comparison group; p = 0.846). Of these survivors, one patient was repaired
      while on ECLS, and the remainder underwent repair after decannulation from ECLS.
      All 20 of the remaining candidates for repair survived without need for ECLS.
      Overall survival was 79% versus 56% in the comparison group (p = 0.027).
      CONCLUSIONS: Our current data suggest that very delayed repair of newborns with
      CDHs is associated with an increase in the overall survival and a decrease in the
      use of ECLS when compared with previous experience at this institution.

PMID- 8862391
TI  - Delayed diagnosis in a rural trauma center.
AB  - BACKGROUND: The rapid and accurate diagnosis of all injuries is critical in
      trauma surgery. Injuries not diagnosed after the secondary survey are not without
      serious consequences. Therefore, in an effort to decrease this problem a policy
      was initiated to perform an ongoing serial exam during the entire course of each
      patient's involvement with the trauma team at Saint Francis Medical Center.
      METHODS: Prospective identification and evaluation of patients admitted to a
      single trauma service with delayed diagnosis was done from July 1, 1993, to
      October 31, 1995. RESULTS: Sixty-eight delayed diagnoses were identified in 56
      patients, for an incidence of 3% of the total 1876 patients evaluated. The vast
      majority were nonspinal orthopedic injuries (63%). Of seven missed spinal
      fractures, only one resulted in permanent paralysis. The remaining injuries
      missed were 11 injuries located in the head and neck area, 3 arterial injuries, 3
      pneumothoraces, and 2 small bowel injuries. Thirty-four percent of the patients
      required surgical intervention for these injuries and one patient died because of
      the delay. There was a high association of delayed diagnosis in victims with
      altered mental status, victims intubated in the field, and individuals requiring
      immediate operation. Twenty percent of our total missed injuries could have been
      avoided if a thorough evaluation of initial films had been done. CONCLUSIONS:
      Delayed diagnosis remains a problem in all trauma centers. This study
      demonstrates that to keep this problem at a reasonable rate, we must: (1)
      carefully review initial x rays; (2) repeat any study that is not clear; and (3)
      continue serial examinations of each patient for the entire clinical course.
      Objective and thoughtful discussion of missed injuries on a routine basis will
      also keep this problem minimal.

PMID- 8862392
TI  - Abdominal computed tomography scan as a screening tool in blunt trauma.
AB  - BACKGROUND: One of the most difficult problems in blunt trauma is evaluation for
      potential intraabdominal injury. Admission for serial abdominal exams remains the
      standard of care after intraabdominal injury has been initially excluded. We
      hypothesized a normal abdominal computed tomography (CT) scan in a subgroup of
      minimally injured patients would obviate admission for serial abdominal
      examinations, allowing safe discharge from the emergency department (ED).
      METHODS: We reviewed our blunt trauma experience with patients admitted solely
      for serial abdominal examinations after a normal CT. Patients were identified
      from the trauma registry at a Level 1 trauma center from July 1991 through June
      1995. Patients with abnormal CTs, extra-abdominal injuries necessitating
      admission, hemodynamic abnormalities, a Glasgow Coma Scale less than 13, or
      injury severity scores (ISSs) greater than 15 were excluded. Records of 238
      patients remained; we reviewed them to determine the presence of missed abdominal
      injury. RESULTS: None of the 238 patients had a missed abdominal injury. Average
      ISS of these patients was 3.2 (range, 0 to 10). Discharging these patients from
      the ED would result in a yearly cost savings of $32,874 to our medical system.
      CONCLUSIONS: Abdominal CT scan is a safe and cost-effective screening tool in
      patients with blunt trauma. A normal CT scan in minimally injured patients allows
      safe discharge from the ED.

PMID- 8862393
TI  - Temperature-sensitive mutations in the protein kinase-1 (pk-1) gene of the
      Autographa californica nuclear polyhedrosis virus that block very late gene
      expression.
AB  - We have developed a genetic screen for temperature-sensitive mutations in the
      very late transcription apparatus of the Autographa californica nuclear
      polyhedrosis virus. This method starts with the BacPAKS virus, which has the
      Escherichia coli lacZ gene under the control of the very late polyhedrin
      promoter. The desired mutants are temperature-sensitive for beta-galactosidase
      production and can be complemented by wild-type virus, which lacks the lacZ gene.
      Two mutants created by nitrosoguanidine mutagenesis and identified by this
      screen, and one mutant identified by another screen, have been mapped by marker
      rescue to the viral protein kinase 1 gene (pk-1). The protein kinase genes of
      these three mutant viruses have been sequenced, revealing the same point mutation
      in two of them and a different point mutation in the other. In each case, a
      single amino acid is changed: In two mutants, XF4 and XF5, Asp 92 is changed to
      Asn; in the other mutant, KT800, Thr 204 is changed to lle. Northern blotting of
      RNA made in cells infected by these three mutant viruses has shown that the
      accumulation of very late transcripts (lacZ and p10) is temperature-sensitive,
      but that accumulation of at least one late transcript (vp39) is not temperature
      sensitive. Nuclear run-on transcription assays with two of the mutants indicate
      that very late transcription is somewhat temperature-sensitive, although this
      defect is not as pronounced as the temperature-sensitivity detected by Northern
      blotting. Transcription of at least one late gene (vp39) is not temperature
      sensitive in cells infected by these two mutants. Thus, it appears that the viral
      protein kinase-1 is involved in very late gene expression. Some of this effect is
      at the transcription level, but some may also be exerted at the posttranscription
      level.

PMID- 8862394
TI  - Long-term maintenance of B cell immunity to influenza virus hemagglutinin in mice
      following DNA-based immunization.
AB  - This study demonstrates that gene-gun inoculation of mice with DNA encoding the
      influenza virus hemagglutinin (HA) results in the life-long maintenance of
      protective B cell responses. Using a sensitive single-cell enzyme-linked
      immunospot assay, we show that all of the HA-specific plasma cells are localized
      in the bone marrow and spleen 1 year postimmunization. As a consequence of prior
      virus challenge, only a small population of antibody-forming cells was found in
      the lymphoid tissues associated with the respiratory tract. The tissue
      distribution of HA-specific plasma cells in these mice was identical to the
      profile in infected controls. Complete protection against live virus challenge in
      the aged vaccinated mice did not require prior exposure to virus. Thus,
      immunization with the DNA, vaccine provides long-term protective immunity against
      otherwise lethal infection.

PMID- 8862395
TI  - Induction of apoptosis by calmodulin-dependent intracellular Ca2+ elevation in
      CD4+ cells expressing gp 160 of HIV.
AB  - Human CD4+ cell clones expressing either gp160 or gp120 of HIV-1 under the
      transcriptional control of an inducible promoter were used to examine the role of
      Ca2+ signalling in the induction of apoptosis by envelope glycoproteins.
      Singlecell killing with apoptosis was induced in the cells expressing gp 160
      while no such apoptosis was found in the cells expressing gp 120. An increase of
      intracellular Ca2+ was found in the gp 160-expressing cells but not in the gp 120
      expressing cells as determined by Intracellular Ca2+ imaging analysis before the
      appearance of DNA fragmentation. W7, a calmodulin antagonist, blocked the
      elevation of Ca2+ as well as the resultant DNA fragmentation, which thus implies
      that the calmodulin-dependent intracellular Ca2+ release system is first
      activated by gp 160 and thereafter apoptosis takes place. The above results thus
      indicate that Ca2+ signalling plays a crucial role in the apoptosis accompanying
      the single-cell death induced by gp 160 in CD4+ cells.

PMID- 8862396
TI  - Effects of adenovirus E1A protein on interferon-signaling.
AB  - We have previously shown that adenovirus E1A proteins can block interferon-alpha
      (IFN-alpha)-signalling. In the current study, we examined if the same is true for
      IFN-gamma signaling. Cotransfection experiments showed that both 289R and 243R
      forms of E1A could block the expression of an IFN-gamma-inducible reporter gene.
      Similarly, in an E1A-expressing HeLa cell line IFN-gamma failed to induce the
      synthesis of IRF-1 mRNA. This failure was due to a block in activation of the
      crucial trans-acting factor, GAF, which in turn was due to the lack of IFN-gamma
      activated tyrosine phosphorylation of the STAT1 alpha protein in E1A-expressing
      cells. The above defect could be attributed to a reduced level of STAT1 alpha
      protein. The level of p48 protein, which is required for IFN-alpha signaling, was
      also lowered. However, the level of lak-1 protein, one of the tyrosine kinases
      necessary for both IFN-alpha and IFN-gamma signalling, was comparable in the E1A
      expressing and the control cells. These results indicate that the observed
      inhibition of IFN signalling in E1A-expressing cells is a consequence of a lower
      abundance of the necessary trnas-acting factors.

PMID- 8862397
TI  - Effects of P2 cleavage site mutations on poliovirus polyprotein processing.
AB  - The poliovirus genome comprises a single open reading frame which is translated
      to give one large polyprotein. The proteolytic cascade involved in the processing
      of this polyprotein is not yet understood in full detail,particularly concerning
      the processing of P2-P3, the precursor to the viral nonstructural polypeptides,
      2A, 2B, 2C, 3A, 3B, 3C, and 3D. To investigate the possibility that the cleavage
      events within P2 and at the 2C/3A junction occur in an ordered fashion, we used
      oligonucleotide-directed mutagenesis of poliovirus cDNA to modify the 3C(prn)
      mediated cleavage sites. The Gin residue of the Gin-Gly sequence at the 2A/2B,
      2B/2C, and 2C/3A junctions in the poliovirus polyprotein was replaced by Asn,
      Glu, Asp, or Lys. The effects of each of these substitutions were studied in vivo
      after transfection onto HeLa cells and in vitro in a cell-free translation assay,
      using full-length mutated RNA transcripts. Only the mutant with the Glu-Gly
      sequence at the 2C/3A junction was viable. Analysis of the in vitro processing
      profiles showed that the efficiency of the 3C protease cleavage at any of the
      sites in P2 was in the following order: Gin-Gly > Glu-Gly > Asn-Gly. No cleavage
      could be detected with the Asp-Gly or Lys-Gly sequence at any junction. Lack of
      2A/2B or 2B/2C cleavage had no consequences on the cleavage efficiency at other
      Gin-Gly sites in the polyprotein. Abolition of cleavage at the 2C/3A junction did
      not prevent the generation of the 2A, 2B, and 3CD polypeptides. Thus, these
      polypeptides. Thus, these polypeptides could be produced independently of the
      generation of the P2 and P3 precursors.

PMID- 8862398
TI  - Secondary structure model of the coat protein gene of turnip yellow mosaic virus
      RNA: long, C-rich, single-stranded regions.
AB  - The RNA of all tymoviruses, a group of ssRNA plant viruses, has a base
      composition that is different from that of most other viruses. The excess of
      cytosines (35-42%) and the low number of guanosines (15-17%) must impel an RNA
      structure with a relatively low amount of base pairing and a high incidence of
      unpaired cytosines. These unpaired cytosines probably function in RNA-protein
      interactions. To gain Insight into the way the RNA is positioned inside the
      virion, the secondary structure has been determined of a part of TYMV RNA,
      including the so-called tymobox, the coat protein gene, and the 3' untranslated
      region, by structure probing, sequence comparison, and computer predictions.
      Conservation of secondary structure elements in tymoviruses is not high and does
      not parallel the conservation of the primary structure. A combination of
      structure prediction and probing experiments, however, results in a model
      consisting of structured domains of 100-200 nucleotides interspersed by long
      unpaired cytosine-rich regions. The latter may interact with the coat protein
      inside the virion. The structure of some functionally interesting regions of the
      3' part of TYMV RNA is also discussed.

PMID- 8862399
TI  - Inhibition of puumala and tula hantaviruses in Vero cells by MxA protein.
AB  - Human MxA protein is a type I Interferon-inducible intracytoplasmic protein,
      which mediates antiviral actions against a variety of negative-strand RNA viruses
      including influenza A, measles, and vesicular stomatitis viruses. Recently, it
      has also been shown that several members of the Bunyaviridae family are inhibited
      by MxA protein. The hantavirus genus in the Bunyaviridae family includes
      important human pathogenic viruses, e.g., Puumala (PUUV), Hantaan, and Sin Nombre
      viruses. Tula virus (TULV) is a new member of the genus, but its pathogenicity in
      man remains to be determined. As assumed by the similarities in replication
      strategy. MxA would be a good candidate molecule for antiviral action against
      these viruses, also. To gain more insight into the MxA action on PUUV, we studied
      PUUV and TULV replication in stably MxA genetransfected Vero cells. We show that
      MxA protein has the capacity to inhibit both viral protein and RNA accumulation
      in virus-infected cells. We also studied PUUV and TULV infection in MxA
      transfected U-937 cell clones. In these cell lines both hantaviruses grew poorly,
      independent of whether the cells were expressing MxA or not Whether cell line
      specific differences in the antiviral activity of MxA protein against
      hantaviruses exist cannot be conclusively determined due to the lack of
      productive infection of PUUV and TULV in U-937 cells.

PMID- 8862400
TI  - Regulation of p53 gene expression by a poxviral transcription factor.
AB  - Identification of regulators of p53 expression is a crucial step in understanding
      the diverse functions of p53 and its role in cellular homeostasis and
      responsiveness to insult. Several viral proteins inactivate p53 as a modulator of
      cell cycle progression and apoptosis. Here, we report that a unique
      leporipoxviral transcription factor greatly increases levels of p53 mRNA. C7, an
      early transcription factor from malignant rabbit fibroma virus (MV), is an
      important determinant of MV virulence. Its effects on cellular gene expression
      were studied both during MV infection and in isolation, with C7 DNA cloned into a
      pKC4 expression plasmid. In both settings, C7 caused increased p53 mRNA levels.
      The increased p53 mRNA reflected new transcription. C7-induced increased
      transcription was selective: mRNAs for some cellular genes increased but those
      for many other genes (e.g., Bc12) were unchanged. Immunoblot and
      immunohistochemical analysis of pKC7-transfected and MV-infected cells showed
      that increased transcription led to an increase in p53 protein. EMSA analysis
      suggested that C7 bound the human p53 promoter between -240 and -614 bp. These
      studies document the direct effects of a viral transcription factor on cellular
      gene expression, specifically that it upregulates p53 transcription.

PMID- 8862401
TI  - Fatal Sindbis virus infection of neonatal mice in the absence of encephalitis.
AB  - A comparative pathogenesis study was performed in neonatal mice using a
      molecularly cloned laboratory variant of Sindbis strain AR339, designated TRSB,
      and a single-site attenuated mutant of TRSB derived by site-directed mutagenesis
      of the E2 glycoprotein from Ser to Arg at residue 114 (TRSBr114). TRSB caused
      100% mortality with an average survival time of 3.0 +/- 0.7 days, whereas mice
      inoculated with TRSBr114 exhibited an attenuated disease course with 46%
      mortality and an extended average survival time of 7.5 +/- 3.4 days for those
      animals that died. Reduced virulence of TRSBr114 was characterized by delayed
      appearance of detectable virus, relative to TRSB, and by lower peak virus titers
      in both sera and brains of infected mice. TRSB infection induced very high peak
      serum titers of interferon alpha/beta (215,000 units/ml compared to 2100 units/ml
      for TRSBr114). In situ hybridization analysis demonstrated replication of TRSB in
      brain, but only minimal histopathological changes and no evidence of encephalitis
      were observed. However, extensive extraneural lesions and viral replication were
      found in skin, connective tissue, and muscle. Moreover, dramatic involution of
      the thymus and loss of hematopoietic tissues were observed in the absence of
      virus replication at these sites, suggesting the involvement of a systemic
      physiological stress response in TRSB infection. TRSBr114 infection did not cause
      thymic lesions. Otherwise, the attenuated mutant demonstrated a similar pattern
      of tissue and organ involvement, but lesions and positive in situ hybridization
      signal were much more limited in scope and intensity compared to TRSB. TRSBr114
      infected mice developed myositis and encephalomyelitis approximately 6 days
      postinfection. Therefore, TRSB-infected animals may succumb to an early syndrome
      associated with the stress response, preventing their survival for a time
      sufficient for the development of encephalitis. Alternatively, a systemic stress
      response, as evidenced by thymic involution, may result in immunosuppression,
      thus contributing to the absence of encephalitis. In any event, the attenuating
      mutation in the E2 glycoprotein significantly altered the course of Sindbis
      induced disease by limiting virus replication and associated damage early in
      infection. Mutant-infected animals survived beyond Day 4 and progressed to a
      classical encephalomyelitis from which about half recovered.

PMID- 8862402
TI  - Assembly of African Swine fever virus: quantitative ultrastructural analysis in
      vitro and in vivo.
AB  - African swine fever virus is an icosahedral double-standed DNA virus which
      replicates in the cytoplasm of porcine monocytic cells. Progeny virus particles,
      like poxviruses and iridoviruses, are assembled in cytoplasmic inclusions, termed
      virus factories. The formation of these structures in susceptible cells infected
      in vitro with pathogenic and attenuated ASFV isolates has been studied by
      semiquantitative and qualitative electron microscopy. Recognizable virus factory
      elements were detected by B hr postinfection (hpi) and increased significantly in
      profile area between 12 and 18 hpi. The number of virus particles associated with
      the virus factories also increased significantly between 12 and 24 hpi. These
      included particles with ("full") and without ("empty") a nucleo-protein core.
      Similar results were obtained for both pathogenic (Malawi) and attenuated
      (Uganda) virus isolates, but the replication of pathogenic virus in the
      macrophage was more efficient than that of the attenuated virus in a porcine
      kidney cell line, where a relatively higher percentage of defective "empty"
      particles were observed. Analysis of virus factory formation was also done
      directly on lung and liver tissue from a pig infected with the highly pathogenic
      Malawi virus isolate. The in vivo data for virus factory area and particle number
      in both pulmonary intravascular macrophages and liver Kupffer cells at Day 4
      postinfection were similar to those observed in vitro. As expected, using
      postembedding immunoelectron microscopy, DNA (both cellular and viral) was
      detected in the cell nucleus, cytoplasmic virus, and mature extracellular virus.
      More interestingly, DNA was absent in the cytoplasm, but readily observed in
      virus factories. This DNA, which we presume to be viral, was found in close
      association with membrane-like material and "empty" particles, suggesting that
      the virus DNA may enter a partially formed capsid which is then sealed in order
      to develope into a fully assembled particle. According to this hypothesis, ASFV
      morphogenesis involves the initial formation of "empty" particles within the
      virus factory. The adjacently formed nucleo-protein material is then inserted
      into the "empty" particles, as has been described for poxviruses. These particles
      then mature in to the "full" particles and leave the virus factory as a prelude
      to release from the cell by budding.

PMID- 8862403
TI  - Hepatitis C virus core protein: carboxy-terminal boundaries of two processed
      species suggest cleavage by a signal peptide peptidase.
AB  - The expression and processing of hepatitis C virus core protein was analyzed. Two
      protein bands, 21 kDa (P21), corresponding to the full-length core, and 19 kDa
      (P19), were detected as major products when core protein was expressed in the
      standard rabbit reticulocyte lysate system or in Sf9 insect cells. Core proteins
      with amino-terminal hexa-histidine tags were expressed which allowed the
      purification of the hexa-histidine P19 core with NI(2+)-NTA columns. With the
      help of mass spectrometry, the molecular weight of hexa-histidine-P19 was
      analyzed and its carboxy-terminus could be calculated. Fusion proteins of
      truncated core/core-E1 species fused to mouse dihydrofolate reductase (mDHFR)
      showed cleavage in the expected region. Cleavage sites could be determined by
      amino-terminal protein sequencing of the DHFR-fusion partner. Our data show that
      there are not one but two core products with an apparent molecular weight of
      about 19 kDa, ending either at amino acid leucine 179 or leucine 182,
      respectively. These cleavages in the hydrophobic, carboxy-terminal region of HCV
      core suggest processing by (a) recently proposed eucaryotic signal peptide
      peptidase(s) (F. Lyko et al. (1995) J. Biol. Chem. 270, 19873-19878).
      Furthermore, our results demonstrate that cleavage at these sites and the
      formation of the P19 species does not require previous processing at the
      signalase site (position 191/192) of the HCV-polyprotein.

PMID- 8862404
TI  - A murine host cell factor required for nicking of the dimer bridge of MVM
      recognizes two CG nucleotides displaced by 10 basepairs.
AB  - During replication of the minute virus of mice (MVM) genome, a dimer replicative
      form (RF) intermediate is resolved into two monomer RF molecules in such a way as
      to retain a unique sequence within the left hand hairpin terminus of the viral
      genome. Although the proposed mechanism for resolution of the dimer RF remains
      uncertain, it likely involves site-specific nicking of the dimer bridge. The RF
      contains two double-stranded copies of the viral genome joined by the extended 3'
      hairpin. Minor sequence asymmetries within the 3' hairpin allow the two halves of
      the dimer bridge to be distinguished. The A half contains the sequence [sequence:
      see text], whereas the B half contains the sequence [sequence: see text]. Using
      an in vitro assay, we show that only the B half of the MVM dimer bridge is nicked
      site-specifically when incubated with crude NS-1 protein (expressed in insect
      cells) and mouse LA9 cellular extract. When highly purified NS-1, the major
      nonstructural protein of MVM, is used in this nicking reaction, there is an
      absolute requirement for the LA9 cellular extract, suggesting a cellular factor
      (or factors) is (are) required. A series of mutations were created in the
      putative host factor binding region (HFBR) on the B half of the MVM dimer bridge
      adjacent to the NS-1 binding site. Nicking assays of these B half mutants showed
      that two CG motifs displaced by 10 nucleotides are important for nicking. Gel
      mobility shift assays demonstrated that a host factor(s) can bind to the HFBR of
      the B half of the dimer bridge and efficient binding depends on the presence of
      both CG motifs. Competitor DNA containing the wild-type HFBR sequence is able to
      specifically inhibit nicking of the B half, indicating that the host factor(s)
      bound to the HFBR is(are) essential for site-specific nicking to occur.

PMID- 8862405
TI  - Isolation and characterization of Whitewater Arroyo virus, a novel North American
      arenavirus.
AB  - Rodents are principal hosts for each of the well-characterized arenaviruses.
      Prior to the present study, Tamiami (TAM) virus was the sole arenavirus known to
      be indigenous to North America; it has been isolated only from southern Florida
      where its primary host is the cotton rat Sigmodon hispidus. Recently, arenavirus
      antibody was found in Neotoma albigula woodrats collected from the southwestern
      United States. The purpose of the present study was to isolate and characterize
      the arenavirus associated with N. albigula. Three isolates of a novel arenavirus
      (proposed name "Whitewater Arroyo," WWA) were recovered from two arenavirus
      antibody-positive N. albigula collected from Whitewater Arroyo in McKinley
      County, New Mexico. Two-way serologic tests indicated that WWA virus is
      antigenically distinct from other arenaviruses but most closely related to TAM
      virus. Phylogenetic analysis of nucleocapsid protein gene sequence data showed
      that WWA virus is a novel arenavirus that is genetically most closely related to
      TAM virus. The recovery of WWA virus from antibody-positive N. albigula suggests
      that WWA virus infection in this species can be chronic and thus that N. albigula
      is a reservoir host of the virus.

PMID- 8862406
TI  - NP:P and NP:V interactions of the paramyxovirus simian virus 5 examined using a
      novel protein:protein capture assay.
AB  - Using recombinant proteins extracted from mammalian cells, in a novel
      protein:protein binding assay, direct interaction of the nucleoprotein (NP) of
      simian virus 5 with the phosphoprotein (P) and V protein (V) was demonstrated.
      The amount of NP bound by V was found to be significantly less than that bound by
      P. Furthermore, preabsorption of NP with P removed the fraction of NP that could
      be bound by V, but preabsorption of NP with V did not remove all the NP that
      could be bound by P. These results suggested that V bound a subpopulation of the
      NP recognised by P. Further analysis revealed that P bound both soluble and
      homopolymeric forms of NP, while V bound only the soluble form; thus
      demonstrating that the binding sites on P and V, for soluble NP, are located
      within the N-terminal domain common to both P and V proteins. A monoclonal
      antibody, which recognised an epitope in the unique C-terminus of P, blocked the
      binding of P to polymeric NP but not to soluble NP. These results also suggest
      that there are two binding sites on NP for P, the site that interacts with the
      P/V common domain being either hidden or conformationally altered in polymeric
      NP.

PMID- 8862407
TI  - Resistance to tomato yellow leaf curl geminivirus in Nicotiana benthamiana plants
      transformed with a truncated viral C1 gene.
AB  - The C1 gene of tomato yellow leaf curl geminivirus (TYLCV) encodes a
      multifunctional protein (Rep) involved in replication. A truncated form of this
      gene, capable of expressing the N-terminal 210 amino acids (aa) of the Rep
      protein, was cloned under the control of the CaMV 35S promoter and introduced
      into Nicotiana benthamiana using Agrobacterium tumefaciens. The same sequence was
      also cloned in antisense orientation. When self-pollinated progeny of 19 primary
      transformants were tested for resistance to TYLCV by agroinoculation, some plants
      proved to be resistant, particularly in the sense lines. Two such lines were
      further studied. The presence of the transgene was verified and its expression
      was followed at intervals. All plants that were resistant to TYLCV at 4 weeks
      postinoculation (wpi) contained detectable amounts of transgenic mRNA and protein
      at the time of infection. Resistance was overcome in a few plants at 9 wpi, and
      in most at 15 wpi. Infection of leaf discs derived from transgenic plants showed
      that expression of the transgene correlated with a substantial reduction of viral
      DNA replication. Cotransfections of tobacco protoplasts demonstrated that
      inhibition of viral DNA replication requires expression of the truncated Rep
      protein and suggested that the small ORF C4, also present in our construct, plays
      no role in the resistance observed. The results obtained using both transient and
      stable gene expression systems show that the expression of the N-terminal 210 aa
      of the TYLCV Rep protein efficiently interferes with virus infection.

PMID- 8862408
TI  - Sin Nombre virus mRNA synthesis.
AB  - Sin Nombre (SN) virus is the major etiologic agent of hantavirus pulmonary
      syndrome, a severe respiratory disease with high mortality. Like other
      hantaviruses, SN virus causes an inapparent chronic infection of the natural
      rodent reservoir and tends to grow slowly and produce little cytopathic effect
      even in highly susceptible Vero E6 tissue culture cells. An
      electrochemiluminescent quantitative PCR approach was developed to allow
      examination of SN virus RNA transcription in synchronously infected cells.
      Although virion particles contain equimolar ratios of the three negative-strand
      genome RNA segments (S, M, and L), rates and levels of accumulation of the
      corresponding N, GPC, and L viral mRNAs varied. The smallest mRNA (N) was
      detectable earliest and plateaued at the highest level, where as the largest mRNA
      (L) appeared latest and at the lowest plateau level. In addition, all three mRNAs
      were found to share a common 5' capped primer initiation mechanism, but appeared
      to have different mRNA termination mechanisms. The N mRNA 3' terminus mapped to
      position 1435 on the S segment, in close proximity to a CCC-rich suspected
      transcription termination motif. The GPC mRNA 3' terminus contained a poly(A)
      tall and mapped to a U8 transcription termination-polyadenylation motif
      reminiscent of those seen in other negative-strand RNA viruses. Finally, the L
      mRNA 3' terminus appeared identical to the L segment antigenome 3' terminus.

PMID- 8862409
TI  - Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively
      infected cells in late G1.
AB  - Human embryonic lung fibroblasts (LU) can be productively infected with human
      cytomegalovirus (HCMV). During the course of productive infection, the virus
      elicits a number of responses that resemble certain aspects of G1 cell cycle
      progression. The virus activates cyclin E/Cdk2 kinase in both subconfluent, serum
      arrested, and density-arrested cultures. Activation of cyclin E-dependent kinase
      is due, in part, to induction of cyclin E and, in part, to inhibition of the
      cyclin kinase inhibitors, Cip1 and Kip1. However, G1 progression is incomplete in
      HCMV-infected cells. Neither cyclin A nor cyclin D is induced, and cellular DNA
      synthesis does not occur if one takes care to avoid addition of fresh serum to
      serum-starved cultures. The data indicate that the virus induces a state of late
      G1 arrest, in which cyclin E/Cdk2 activates nucleotide metabolism and other
      biosynthetic processes that are necessary for viral replication. Failure to
      activate host cell DNA synthesis ensures that the virus will have uncompleted
      access to such precursors.

PMID- 8862410
TI  - Viral isolates derived from simian varicella epizootics are genetically related
      but are distinct from other primate herpesviruses.
AB  - Epizootics of a natural varicella-like disease occur in populations of nonhuman
      primates. Several primate herpesviruses have been isolated from these epizootics,
      but the relatedness of these isolates to each other is not well-defined. In this
      study, we demonstrated that the restriction endonuclease (REn) profiles of four
      epidemiologically distinct isolates were similar, although not identical,
      indicating that simian varicella epizootics are caused by various strains of
      simian varicella virus (SVV). The genetic variation among the isolates did not
      map to a specific region of the SVV genome and REn differences were detected
      within the SVV DNA long component and the inverted repeat region. Southern blot
      hybridization demonstrated that SVV is more closely related to varicella-zoster
      virus than to other primate herpesviruses. The study indicates that the current
      herpesvirus classification scheme should be changed to include SVV as a single
      taxonomic group within the Varicellovirus genus of alphaherpesviruses. In
      addition, REn profiles of SVV isolates, derived from primary and secondary
      episodes of simian varicella in the same monkey, were identical, providing
      evidence for SVV reactivation in a latently infected monkey.

PMID- 8862411
TI  - Induction of pleckstrin by the Epstein-Barr virus nuclear antigen 3 family.
AB  - The Epstein-Barr virus (EBV) encoded nuclear antigens, EBNA-3, -4, and -6 (EBNA 3
      family) are expressed in latently infected human B-cells and are involved in the
      transformation of lymphocytes by EBV. Human Burkitt's lymphoma (BL) dG75 cells
      which stably expressed either the complete EBNA 3 gene family or the vector alone
      were generated and changes in gene activity in these transfectants were assayed
      using the differential display of mRNA technique. For the first time, the human
      gene pleckstrin, which is thought to be involved in signalling and
      differentiation of hemopoietic cells, was found to be upregulated in the presence
      of the EBNA 3 protein family, but not in cells expressing the individual EBNA-3, 
      4, or -6 gene. Pleckstrin was increased up to sevenfold in different cell clones
      and the bulk culture of EBNA 3 gene family expressing cells as demonstrated by
      Northern blot. RT-PCR, and immunoblot in contrast to EBV-negative BL cells,
      pleckstrin RNA and protein were highly expressed in EBV growth transformed
      lymphoblastoid cell lines which are thought to play an important role in EBV
      persistence in vivo. These data suggest that induction of pleckstrin might be
      important for the EBV-controlled activation of cells and offers a unique
      biological system for analyzing pleckstrin function.

PMID- 8862412
TI  - Genetic variation in neuraminidase genes of influenza A (H3N2) viruses.
AB  - Nucleotide sequences of the neuraminidase (NA) genes of 33 influenza A (H3N2)
      epidemic strains isolated between 1968 and 1995 were analyzed to determine their
      evolutionary relationships. Phylogenetic analysis using the DNA maximum
      likelihood method indicates that the NA genes of recent H3N2 field strains, like
      their hemagglutinin genes (HA), have evolved as two distinct lineages represented
      by the vaccine strains. A/Beijing/353/89 and A/Beijing/32/92 for A/Shanghai/24/
      90). Furthermore, genetic reassortment of NA genes between the two lineages
      occurred during their circulation. Genetic reassortants, which bear an
      A/Beijing/32/92-like HA and an A/Beijing/353/89-like NA, have circulated
      worldwide and are representative of current influenza A (H3N2) epidemic strains.
      The mutation rate of the NA gene was found to be 2.28 x 10(-3) per nucleotide
      site per year with 4.2% of the mutations resulting in amino acid substitutions.
      Thirty-five percent of the amino acid substitutions was located in sites
      previously suggested to be reactive to antibody. Amino acid residues involved in
      NA enzyme activity have been conserved. Seven potential glycosylation sites
      identified in the NA of A/Hong Kong/8/68 virus were conserved by the majority of
      isolates, with more recently circulating viruses having an additional
      glycosylation site. Comparison of the rate of amino acid substitutions in the NA
      stalk to that of entire NA revealed high variability in this region. These
      findings demonstrate the importance of closely monitoring both the HA and the NA
      genes of influenza viruses to aid vaccine strain selection.

PMID- 8862414
TI  - Cholesterol-depleted cells that are relatively permissive for Semliki Forest
      virus infection.
AB  - Semliki Forest virus (SFV), an enveloped alphavirus, Infects cells by endocytosis
      followed by low pH-triggered fusion of the virus and endocytic vesicle membranes.
      Progeny virus is released by budding from the cell plasma membrane. In vitro, SFV
      fusion with artificial liposomes is triggered by low pH and is dependent on the
      presence of cholesterol and sphingolipid in the target liposome membrane. In
      tissue culture, both SFV fusion and virus exit are strongly cholesterol-dependent
      when assayed in cholesterol-depleted insect cells. We here describe the
      preparation of insect cells that while not containing detectable amounts of
      cholesterol, have adapted to sterol-depleted conditions, resulting in a more
      permissive phenotype for SFV infection. Although still less efficient at
      supporting SFV infection than control cholesterol-containing cells, the adapted
      cells show a 45-fold increase in primary infection by SFV, increased release of
      progeny virus, and enhanced virus growth kinetics compared to nonadapted
      cholesterol-depleted cells. The adapted cells are also about 85-fold more
      permissive for low pH-induced fusion of SFV with the plasma membrane, suggesting
      that adaptation correlates with a change in the cell membrane.

PMID- 8862413
TI  - Interaction of mouse adenovirus type 1 early region 1A protein with cellular
      proteins pRb and p107.
AB  - We demonstrated functional associations between mouse adenovirus type 1 (MAV-1)
      early region 1A (E1A) protein and both the mouse retinoblastoma protein (pRb) and
      the mouse pRb-related protein, p107. Interactions between MAV-1 E1A and mouse pRb
      or mouse p107 proteins were examined in infected cell lysates using a mouse
      embryonic fibroblast cell line infected with wild-type and mutant MAV-1 viruses.
      Using a polyclonal antibody to MAV-1 E1A, exogenously added mouse pRb or mouse
      p107 was coimmunoprecipitated from wild-type, dIE105 (CR1 delta)-, and dIE106
      (CR3 delta)-infected cell lysates. No coimmunoprecipitation was seen with cell
      lysates from dIE102 (CR2 delta) or pmE109, a mutant virus that produces no
      detectable E1A protein due to an ATG to TTG point mutation in the initiator
      methionine. Introduction of mouse pRb into SAOS-2 cells resulted in a flat and
      enlarged cell phenotype, whereas cotransfection of mouse pRb and MAV-1 E1A
      resulted in a significant reduction of flat cells, presumably due to E1A binding
      pRb. CR1 delta and CR2 delta E1A proteins were less effective at reducing the
      number of flat, enlarged cells induced by pRb expression than were the CR3 delta
      or wild-type E1A proteins. The reduced ability of these mutants to inactivate pRb
      relative to wild-type E1A correlated with their reduced ability to bind pRb in
      the in vitro coimmunoprecipitation experiments. As a measure of p107/MAV-1 E1A
      complex formation in MAV-1-infected cells, we used mobility shift assays to
      examine cell extracts for the presence of p107-containing E2F protein-DNA
      complexes. Mock-, dIE102-, and pmE109-infected cell extracts formed a p107
      containing complex, whereas wild-type-infected cell extracts did not. Thus the
      formation of a p107-E2F complex in wild-type- or these mutant-infected extracts
      inversely correlated with the presence of E1A-p107 complexes identified in the
      vitro coimmunoprecipitation experiments. This is consistent with E1A-p107
      complexes forming in wild-type MAV-1-infected cells.

PMID- 8862415
TI  - Activation of the HTLV-I long terminal repeat by the hepatitis B virus X protein.
AB  - The human T-cell leukemia virus type I (HTLV-I) Tax protein and the hepatitis B
      virus (HBV) X protein have each been shown to activate transcription of their
      respective viral promoters as well as a subset of cellular gene promoters. Here
      we show that the HTLV-I long terminal repeat (LTR) is responsive to HBV X
      transactivation. Maximum levels of X-mediated transactivation of the LTR were 8
      fold. An X-responsive-region (XRR) of the LTR is located between nucleotides -355
      and -276 and contains an AP-2 binding site, a previously recognized X-responsive
      element. We demonstrated that Tax and X synergize to activate transcription from
      the HTLV-I LTR, although the AP-2 binding site was not required for this synergy.
      These results raise the possibility that the HBV X protein may affect the level
      of HTLV-I gene expression in co-infected individuals.

PMID- 8862416
TI  - Differential regulation of the HIV-1 LTR by specific NF-kappa B subunits in HSV-1
      infected cells.
AB  - Previous studies have shown that expression of HIV-1 provirus was enhanced in
      cells co-infected with the herpes virus and that HSV-1-mediated induction of the
      HIV-1 provirus expression involved both NF-kappa B-dependent and NF-kappa B
      independent mechanisms. Nuclear NF-kappa B complexes could be detected
      approximately 8 hr after HSV-1 infection. Using NF-kappa B-specific antibodies in
      a mobility shift assay, we have found that HSV-1 increases binding of p50, p65,
      and c-rel to the HIV-1 NF-kappa B probe in both Jurkat T cells and NIH/3T3 cells
      HSV-1 infection also increases transiently the levels of p50 mRNA but an increase
      in the level of p65 mRNA was not detected. Furthermore, HSV-1 infection induces a
      rapid degradation of the I kappa B alpha protein. Transfection of HIV-1 LTR CAT
      into cell lines which overexpressed individual NF-kappa B proteins showed the
      highest constitutive expression of CAT activity in cells overexpressing p65.
      Infection with HSV-1 further enhanced the expression of HIV-1 LTR CAT in cell
      lines producing p52, p100, and c-rel. In contrast, HSV-1 did not significantly
      enhance the expression of HIV-1 LTR CAT in cell lines overexpressing p105 and 1
      kappa B gamma. In the transient expression assay the p65/c-rel heterodimer was
      the most effective inducer of the HIV-I LTR expression. Thus it appears that p65
      plays a limited role in the NF-kappa B-dependent activation of the HIV-1 LTR
      following HSV-1 infection and that the stimulation is mediated by the p50/p65 and
      p65/c-rel heterodimers. Thus the magnitude of HIV-1 provirus induction depends on
      the relative levels of NF-kappa B subunits present in the infected cells.

PMID- 8862417
TI  - Mml1, a new common integration site in murine leukemia virus-induced promonocytic
      leukemias maps to mouse chromosome 10.
AB  - MuLV-induced myeloid leukemias (MML) having promonocytic characteristics are
      produced with high incidence in some strains of adult mice that are undergoing
      chronic peritoneal inflammation. Previously we showed that many leukemias have
      rearrangements of the c-myb locus due to insertional mutagenesis, however, we
      also identified a number of leukemias that had proviral integrations in the
      absence of c-myb rearrangement in the present study, a new locus, Mml1, was found
      to be a target of insertional mutagenesis in 10 of the promonocytic leukemias
      that lacked c-myb alterations. Chromosomal mapping studies, performed using
      progeny from interspecies backcross mice generated by mating (BALB/cAn x M.
      spretus)F1 females to BALB/cAN males, determined that Mml1 is located on the
      proximal end of mouse chromosome 10. Interestingly, there were no recombinants
      between c-myb and Mml1 in 101 backcross progeny and Mml1 was mapped approximately
      20-25 kb upsteam of c-myb. Interestingly, c-myb mRNA and Myb protein are
      expressed at levels similar to the levels observed in myeloid progenitor cells,
      but are not overexpressed. It is anticipated that future experiments will
      determine whether Mml1 integration prevents down regulation of c-myb expression
      or activates another gene on chromosome 10.

PMID- 8862418
TI  - Structure-function analysis of the Autographa californica multinucleocapsid
      nuclear polyhedrosis virus homologous region palindromes.
AB  - Homologous regions (hrs), which are present at eight dispersed locations on the
      Autographa californica multinucleocapsid nuclear polyhedrosis virus genome, are
      composed of repeated imperfect palindromes within directly repeated sequences.
      Hrs act as transcriptional enhancers of RNA polymerase II-mediated transcription
      and as origins of DNA replication when incorporated into plasmids and tested in
      transient replication assays. To characterize the physical structure of these
      elements and to determine the role that mismatched nucleotides may play in hr
      function, oligonucleotides containing a consensus mismatched "imperfect"
      palindrome and a closely related "perfect" palindrome were synthesized. These
      sequences were cloned into individual plasmids and tested for their ability to
      form cruciform structures using nuclease P1 assays and two-dimensional (2-D) gel
      analyses of topoisomers. The perfect palindrome formed a cruciform structure and
      the energy requirement for its formation was predicted to occur under
      physiological conditions. In contrast, the construct containing an imperfect
      palindrome did not form a cruciform under these conditions. Both hr constructs
      were found to bind IE-1 in electrophoresis mobility shift assays and act as
      enhancers when cis-linked to the baculovirus 39K early gene promoter. However, a
      single oligonucleotide containing the palindrome sequence did not bind IE-1 when
      annealed under conditions conducive to hairpin formation.

PMID- 8862419
TI  - Requirement of caprine arthritis encephalitis virus vif gene for in vivo
      replication.
AB  - Replication of vif-caprine arthritis encephalitis virus (CAEV) is highly
      attenuated in primary goat synovial membrane cells and blood-derived macrophages
      compared to the wild-type (wt) virus. We investigated the requirement for CAEV
      Vif for in vivo replication and pathogenicity in goats by intra-articular
      injection of either infectious proviral DNA or viral supernatants. Wild-type CAEV
      DNA or virus inoculation induced persistent infection resulting in severe
      inflammatory arthritic lesions in the joints. We were unable to detect any sign
      of virus replication in vif- CAEV DNA inoculated goats, while vif- CAEV virus
      inoculation resulted in the seroconversion of the goats. However, virus isolation
      and RT-PCR analyses on blood-derived macrophage cultures remained negative
      throughout the experiment as well as in joint or lymphoid tissues taken at
      necropsy. No pathologic lesions could be observed in joint tissue sections
      examined at necropsy. Goats inoculated with the vif- virus demonstrated no
      protection against a pathogenic virus challenge. These results demonstrate that
      CAEV Vif is absolutely required for efficient in vivo virus replication and
      pathogenicity and provide additional evidence that live attenuated lentiviruses
      have to establish a persistent infection to induce efficient protective immunity.

PMID- 8862420
TI  - Common modular structure of lentivirus LTRs.
AB  - Retroviruses are expressed under the control of viral control regions designated
      long terminal repeats (LTRs), which contain all signals for transcriptional
      initiation as well as transcriptional termination. However, retroviral LTRs from
      different species within a common genus, such as Lentivirus, do not show
      significant overall sequence homology. We compiled a model of the functional
      organization of 20 Lentivirus LTRs which we show to recognize all known
      Lentivirus LTRs. To this end we combined our previously published methods for
      identification of transcription elements with secondary structure element
      analysis in a novel modular approach. We deduced descriptions for three new
      Lentivirus-specific sequence elements present in most of the Lentivirus LTRs but
      absent in LTRs of other retrovirus families (B, C, D-type, BLV-HTLV, Spuma). Four
      of the 10 elements defined in our study were primate-specific. We were able to
      deduce a phylogeny based on our model which agrees in general with the phylogeny
      derived from the polymerase genes of these viruses. Our model indicated that more
      than 100 LTRs from the databases are of Lentivirus origin and can be clearly
      separated from all other LTR types (B, C, D, BLV-HTLV, Spuma). This selectivity
      appears to be a unique feature of our modular approach.

PMID- 8862422
TI  - Expression of CD26 does not correlate with the replication of macrophage-tropic
      strains of HIV-1 in T-cell lines.
AB  - Strains of human immunodeficiency virus type 1 (HIV-1) differ significantly in
      both genetic content and biological properties. One of the earliest discovered
      differences between HIV-1 strains was divergence in the relative ability of
      different strains to replicate in either T-cell lines or monocytes/macrophages.
      This observation has led to the suggestion that molecules present on the surface
      of HIV-susceptible cells other than CD4 may interact with gp120 in facilitating
      the entry of HIV-1 into host cell populations. Several reports have suggested
      that CD26, a cell surface protease expressed on many cells of the immune system
      including some CD4+ T-cells and macrophage, may be an accessory molecule for HIV
      1 entry. Recently, it has also been reported that the expression of high levels
      of CD26 correlates with the entry and replication of macrophage-tropic strains of
      HIV-1 in a T-cell line. In this report, we demonstrate that replication of
      macrophage-tropic strains of HIV-1 in T-cell lines is independent of CD26
      expression. From this observation, we conclude that CD26 plays no role in the
      entry of HIV-1 into these cells.

PMID- 8862421
TI  - Comparative properties of feline immunodeficiency virus (FIV) and human
      immunodeficiency virus type 1 (HIV-1) proteinases prepared by total chemical
      synthesis.
AB  - The aspartyl proteinase (PR) encoded by the feline immunodeficiency virus (FIV)
      was prepared by total chemical synthesis. The 116-amino-acid polypeptide chain
      was assembled in a stepwise fashion using a Boc chemistry solid-phase peptide
      synthesis approach and subsequently folded into the biologically active dimeric
      proteinase. The synthetic enzyme showed proteolytic activity against a variety of
      different peptide substrates corresponding to putative cleavage sites of the Gag
      and Gag-Pol polyproteins of FIV. A comparative study with the proteinase of human
      immunodeficiency virus type 1 (HIV-1) showed that the FIV and HIV-1 enzymes have
      related but distinct substrate specificities. In particular, HIV-1 PR and FIV PR
      each show a strong preference for their own MA/CA substrates, despite identical
      amino acid residues at four of seven positions from P3-P4' of the substrate
      including an identical MA/CA cleavage site (between Tyr approximately Pro
      residues). FIV PR also showed a requirement for a longer peptide substrate than
      HIV-1 PR. Defining the similarities and the differences in the properties of
      these two retroviral enzymes will have a significant impact on structure-based
      drug design.

PMID- 8862423
TI  - High Sp1/Sp3 ratios in epithelial cells during epithelial differentiation and
      cellular transformation correlate with the activation of the HPV-16 promoter.
AB  - Gene expression of human papillomavirus type 16 (HPV-16) and other HPV types is
      epithelial specific. Specificity is brought about by synergism between several
      different transcription factors that seem to occur ubiquitously but differ
      qualitatively and quantitatively between cells in which HPV genomes are
      transcriptionally active or inactive. Here, we report on the contribution to this
      combinatorial mechanism by the activator Sp1 and the related antagonist Sp3, both
      of which can bind a single site at the E6 promoter of all genital HPVs. In the Sp
      factor-free background of Drosophila cells, Sp1 activates HPV-16 transcription,
      while Sp3 fails to do so and even inhibits the activation by Sp1. The same
      differential activation occurs in the case of promoters of the epithelial
      specific cellular genes encoding keratin 18 and E-cadherin. All cell types that
      we examined contain similar amounts of Sp3 factor. In contrast, Sp1 levels,
      determined by supershifts and Western blots, are higher in several human
      epithelial cell lines that support HPV transcription than in human fibroblasts,
      liver, and muscle cells. This suggests that cell-type differential transcription
      is regulated by Sp1 and Sp3. In primary keratinocytes, Sp3 levels exceed those of
      Sp1. This ratio became inverted after differentiating these cells in high
      calcium, or methyl cellulose containing medium. The simultaneous transcriptional
      stimulation of the HPV promoter points to a role of the Sp1-Sp3 antagonism during
      a differentiation of stratified epithelia in vivo, as these culture techniques
      mimick this process in vitro. Transformation in vivo or in vitro seems to
      override these cell-type-specific controls and leads to a general increase of Sp1
      activity.

PMID- 8862424
TI  - HIV-1 Nef association with cellular serine kinase correlates with enhanced virion
      infectivity and efficient proviral DNA synthesis.
AB  - We previously reported on the association of Nef with a cellular serine kinase
      (E.T. Sawal et al., Proc. Natl. Acad. Sci. USA 91, 1539-1543, 1994). In the
      present study, we further define the Nef sequence requirements for this kinase
      association and investigate the effect of this kinase association on functions of
      HIV-1 Nef. We observe that, in addition to the membrane targeting signal and the
      conserved arg-arg residues within the core region, mutations in the proline-rich
      domain of Nef also affect its ability to associate with the serine kinase
      activity. The region encompassing the arg-arg residues of Nef is shown to be
      important for Nef-mediated cell-surface CD4 down-modulation as well as
      enhancement of viral growth properties. This is similar to what has previously
      been observed for the membrane targeting site at the N-terminus of Nef. In
      contrast, the proline-rich region of Nef is found to be involved in mediating
      efficient proviral DNA synthesis and the enhanced virion-infectivity function,
      but is not necessary for CD4 down-modulation by Nef. Thus, it appears that serine
      kinase association of Nef is necessary for efficient proviral DNA synthesis and
      for promotion of virion infectivity of Nef viruses, but is dispensable for down
      regulation of the CD4 receptor by Nef. These findings define three functional
      domains of Nef that are required for its interaction with the serine kinase
      activity and suggest that the cellular interaction events via the myristoylation
      and arg-arg regions of Nef lie upstream of the interaction event via the proline
      rich domain.

PMID- 8862425
TI  - HIV-1 particle release mediated by Vpu is distinct from that mediated by p6.
AB  - Vpu and the C-terminal peptide of Gag (p6) are both HIV-1-encoded proteins that
      augment the release of virus particles from cells. We examined the functional
      relationship between these proteins and their activities during particle release.
      Our results indicate that efficient HIV-1 particle release from HeLa and Jurkat
      cells depends on the presence of Vpu. However, Vpu is dispensable for efficient
      release from Cos cells. In contrast, p6 is required for efficient release from
      Cos cells but not from Jurkat or HeLa cells. These data suggest that Vpu and p6
      have distinct activities in virus exit from different cell lines. Intracellular
      proteolytic processing of Gag precursor protein is more complete in Cos cells
      than in HeLa cells. However, this processing has little or no effect on Vpu- or
      p6-mediated particle release. p6 is required for incorporation of yet another
      virus protein (Vpr) into cells but our data suggest that Vpr plays no role in p6
      dependent particle release. Vpu also facilitates the degradation of CD4 in virus
      producing cells but, in contrast to particle release, the ability of Vpu to
      facilitate the degradation of CD4 is not cell line-dependent.

PMID- 8862427
TI  - Expression of human foamy virus reverse transcriptase involves a spliced pol
      mRNA.
AB  - In human foamy virus (HFV) the reverse transcriptase is expressed independently
      of the Gag protein as a 127-kDa Pol precursor molecule. Evaluating the mechanism
      of Pol expression we identified a spliced mRNA which uses the main 5' splice
      donor and a splice acceptor site located in the gag gene. The significance of
      this spliced transcript for HFV Pol expression was studied by constructing a
      virus with a mutated splice acceptor site. This virus was unable to express
      detectable Pol proteins after transient transfection. Replication of the mutant
      was studied by a sensitive assay based on HFV transactivator-stimulated
      expression of an integrated lacZ gene under control of the HFV long terminal
      repeat. Whereas in the first 2 weeks after transfection the mutant replicated 3
      to 5 order of magnitude less well than wild-type virus, extracellular titers
      obtained thereafter were similar to those of wild-type virus. This increase in
      replication competence was accompanied by a reversion of the mutated splice
      acceptor site. The results underlined the importance of the spliced pol
      transcript for HFV replication and pointed to a second mechanism of Pol
      expression. Indicator gene assays suggest that this other mechanism is likely to
      be a transactivator-dependent cryptic promoter in the gag gene which gives rise
      to Pol-encoding transcripts.

PMID- 8862426
TI  - The genome organization and affinities of an Australian isolate of carrot mottle
      umbravirus.
AB  - The genomic sequence of an Australian isolate of carrot mottle umbravirus (CMoV
      A) was determined from cDNA generated from dsRNA. This provides the first data on
      the genome organization and phylogeny of an umbravirus. The 4201-nucleotide
      genome contains four major open reading frames (ORFs). Analysis suggests that
      ORF2 encodes an RNA-dependent RNA polymerase, that ORF4 encodes a movement
      protein, and that the virus has no coat protein gene. The functions of ORFs 1 and
      3 remain unknown. ORF2 is probably translated following ribosomal frameshifting.
      ORFs 3 and 4 are probably translated from a subgenomic mRNA. Sequence comparisons
      showed CMoV-A to be closely related to pea enation mosaic RNA2 (PEMV-RNA2), but
      also to have affinities with the Bromoviridae. These findings shed light on the
      relationships between the luteoviruses, PEMV, and the umbraviruses and on the
      relationships between the carmo-like viruses and the Bromoviridae.

PMID- 8862428
TI  - The effect of regulatory sequence elements upon the initiation of DNA replication
      of the minute virus of mice.
AB  - The minute virus of mice (MVM) genome is a linear single-stranded length of
      approximately 5000 nucleotides of DNA with unique terminal palindromic sequences
      at both ends. The left(3') hairpin is used to prime the initiation of DNA
      synthesis on parental single-strand DNA while the right (5') hairpin or stem-plus
      arms structure can also prime the initiation of DNA synthesis during synthesis of
      dimer and higher oligomers as well as synthesis of progeny single strands.
      Previous studies have shown that if viral duplex DNA was input into an in vitro
      DNA replication system using extracts from uninfected HeLa cells, the 5' end of
      the molecule was able to form a hairpin and initiate DNA synthesis by DNA
      polymerase delta (Cossons et al. (1996), Virology 216, 258-264). In this study,
      the effect of the deletion of known cis-acting genetic elements upon the
      initiation of DNA replication was studied using a series of MVM mutants with
      deletions within the 5' terminal region. Mutants containing deletions of elements
      A (nucleotides 4489-4636), B (nucleotides 4636-4695), and either one or both of
      the 65-bp repeats (nucleotides 4720-4785 and 4785-4849) were used as template in
      the in vitro DNA replication system. When element A was deleted, the efficiency
      of initiation decreased significantly. Subsequent removal of element B, leaving
      just the two 65-bp repeats, restored levels of initiation back to those seen in
      the wild-type genome. In the absence of either A or B both 65-bp repeats were
      necessary for efficient initiation, and removal of one of these repeats caused a
      decrease in efficiency. Thus, element B appeared to have a negative regulatory
      effect (in the absence of element A), and element A appeared to have a positive
      regulatory effect, at least in the presence of element B. These data demonstrate,
      for the first time, a complex interaction between these cis-acting regulatory
      elements which can function as both positive or negative regulators in the
      initiation of MVM DNA replication.

PMID- 8862429
TI  - Transcriptional and translational expression kinetics of the early gene encoding
      the BICP27 protein of bovine herpesvirus type 1.
AB  - The expression kinetics of an essential trans-regulatory protein, ICP27, from
      herpes simplex virus type 1 correspond to that of an immediate-early gene whose
      expression increases rapidly upon infection and then decreases as of 7 hr
      postinfection. In contrast, here we report that the bovine herpesvirus type 1
      (BHV-1) homolog BICP27, a 50-kDa protein, is expressed as an early gene. Both the
      transcript and protein accumulated gradually reaching peak levels at
      approximately 12 hr postinfection, after which point steady state levels were
      maintained up to 24 hr. Thus the expression profiles of ICP27 and BICP27 are
      significantly different, suggesting that they may possess different functions.

PMID- 8862430
TI  - Vaccination with herpes simplex virus type 1 glycoprotein K impairs clearance of
      virus from the trigeminal ganglia resulting in chronic infection.
AB  - Following primary ocular infection, HSV-1 establishes a latent infection in the
      trigeminal ganglia with the complete absence of detectable infectious virus.
      Recently, we showed that vaccination of BALB/cJ with HSV-1 glycoprotein K (gK),
      but not other HSV-1 glycoproteins, significantly exacerbated the severity of HSV
      1-induced ocular disease and herpetic dermatitis (H. Ghiasi et al. J. Virol. 68,
      2347-2354, 1994). We now report that prior vaccination with gK blocked viral
      clearance from trigeminal ganglia until at least Day 56 postinfection, resulting
      in a chronic infection. The significance of this novel finding with respect to
      potential harmful complications associated with the immune response to gK is
      discussed.

PMID- 8862431
TI  - Mapping amino acids of the measles virus hemagglutinin responsible for receptor
      (CD46) downregulation.
AB  - We compared the amino acid sequences of groups of receptor (CD46) downregulating
      and nondownregulating measles virus (MV) hemagglutinins (Hs) and identified seven
      group-specific differences as candidates for the mediation of the observed
      differential effects. Using site-directed mutagenesis, we mutated the chosen
      amino acids of the H of MV-strain WTF (WTF-H), a nondownregulating H, and
      Introduced the corresponding amino acids of Edmonston-H (Edm-H), a downregulating
      H. We identified four amino acids, 211G, 243R, 451V, and 481Y, which influenced
      the downregulative function when introduced into WTF-H. The double mutation 451V
      and 481Y in WTF-H led to a degree of CD46 downregulation comparable to that of
      Edm-H. Conversely, introducing amino acids 451E and 481N into Edm-H resulted in a
      loss of the downregulative function. These results indicate that these amino
      acids play a decisive role in the H-CD46 interaction.

PMID- 8862432
TI  - RNA splice site utilization by simian immunodeficiency viruses derived from sooty
      mangabey monkeys.
AB  - Alternative splicing of the full-length, primary transcript into numerous
      subgenomic mRNAs is one way that lentiviral gene expression is regulated. Because
      the behaviors of different viral isolates might reflect in part differences in
      splicing, we Investigated the patterns of splice site utilization by simian
      immunodeficiency viruses (SIVs)-originally isolated from sooty mangabey monkeys
      (Cercocebus atys) We used reverse transcription-polymerase chain reaction (RT
      PCR), molecular cloning, and DNA sequencing approaches to characterize
      SIVdeltaB670, a pathogenic and neurovirulent isolate, and SIVsmmH4, a related
      molecular clone. The majority of randomly selected SIVdeltaB670 and SIVsmmH4
      partial cDNAs contained tat, rev, nef, and long terminal repeat (LTR) intron
      splice donor and acceptor sites positioned as expected based on the proviral
      sequence of SIVsmmH4. Nearly all (87%) of the partial cDNAs analyzed contained a
      spliced LTR intron. A greater number of partial cDNAs derived from SIVdeltaB670
      infected cells contained putative alternatively spliced introns In comparison to
      SIVsmmH4, including two previously undocumented splice junctions involving the
      LTR intron splice donor. These data provide the first comprehensive analysis of
      splice site utilization by an isolate of SIV in comparison to a related molecular
      clone and the first characterization of SIVsmm splice site utilization.

PMID- 8862433
TI  - A murine and a porcine coronavirus are released from opposite surfaces of the
      same epithelial cells.
AB  - Epithelial cells are important target cells for coronavirus infection. Earlier we
      have shown that transmissible gastroenteritis coronavirus (TGEV) and mouse
      hepatitis coronavirus (MHV) are released from different sides of porcine and
      murine epithelial cells, respectively. To study the release of these viruses from
      the same cells, we constructed a porcine LLC-PK1 cell line stably expressing the
      recombinant MHV receptor cDNA (LMR cells). The MHV and TGEV receptor
      glycoproteins were shown by immunofluorescence to appear at the surface of the
      cells and to be functional so that the cells were susceptible to both MHV and
      TGEV infection. Both coronaviruses entered polarized LMR cells only through the
      apical surface. Remarkably, while the cells remained susceptible to TGEV for long
      periods, infectability by MHV decreased with time after plating of the cells onto
      filters. This was not due to a lack of expression of the MHV receptor, since this
      glycoprotein was still abundant on the apical surface of these cells. TGEV and
      MHV appeared to exit LMR cells from opposite sides. Whereas TGEV was released
      preferentially at the apical membrane, MHV was released preferentially at the
      basolateral surface. These results show that vesicles containing the two
      coronaviruses are targeted differently in LMR cells. We propose that the viruses
      are sorted at the Golgi complex into different transport vesicles that carry
      information directing them to one of the two surface domains. The apical release
      of TGEV and the basolateral release of MHV might be factors contributing to the
      difference in virus spread found between TGEV and MHV in their respective natural
      hosts, the former causing mainly a localized enteric infection, the latter
      spreading through the body to other organs.

PMID- 8862435
TI  - "Oh no!".

PMID- 8862434
TI  - Capsid proteins of cowpea mosaic virus transiently expressed in protoplasts form
      virus-like particles.
AB  - The coding regions for cowpea mosaic virus (CPMV) capsid proteins VP37 and VP23
      were introduced separately into a transient plant expression vector containing an
      enhanced CaMV 358 promoter. Significant expression of either capsid protein was
      observed only in protoplasts transfected simultaneously with both constructs.
      Immunosorbent electron microscopy revealed the presence of virus-like particles
      in extracts of these protoplasts. An extract of protoplasts transfected with both
      constructs together with RNA-1 was able to initiate a new infection, showing that
      the two capsid proteins of CPMV can form functional particles containing RNA-1
      and that the 60-kDa capsid precursor is not essential for this process.

PMID- 8862436
TI  - Buffon's needle statistics are not applicable to calculate the mutation rate or
      the number of structural genes in the human genome.

PMID- 8862437
TI  - Suppression of MHC class I antigens in oncogenic transformants: association with
      decreased recognition by cytotoxic T lymphocytes.
AB  - Cytotoxic T lymphocytes (CTLs) recognize peptide fragments derived from
      endogenous proteins, processed internally, and presented at the cell surface by
      major histocompatibility complex (MHC) class I molecules. The use of specific CTL
      for cancer therapy is limited because of their dependence on effective processing
      and presentation of appropriate antigenic peptides. Structural alterations, like
      point mutation or somatic loss, or dysregulation of key elements in the
      processing or presentation pathway, may allow cells to escape the immune
      surveillance. Indeed, the expression of MHC class I antigens on the surface of
      virus- and oncogene-transformed cells is low and correlates with tumorigenicity.
      Transformation of murine fibroblasts with the ras oncogene results in the
      suppression of cell surface expression of all H-2 loci as determined by FACScan
      analysis using a panel of monoclonal antibodies. We then examined whether the
      oncogene-mediated suppression of MHC class I surface expression was associated
      with reduced recognition of transformants by CD8+ T lymphocytes. Murine T
      lymphoma cells were stably transfected by the Ha-ras oncogene. The transfectants
      expressed distinct levels of the Ha-ras specific protein p21. Again,
      immunofluorescence analysis demonstrated an inverse correlation between oncogene
      and MHC class I surface expression in RMAras transformants. Allogeneic H-2Kb
      restricted cytotoxic T lymphocytes were able to efficiently lyse the parental T
      lymphoma cells. In contrast, the CTL-mediated lysis of ras transformants was
      significantly downregulated compared with untransfected RMA cells. The efficiency
      of CTL-mediated lysis of RMAras cells was directly associated with reduced MHC
      class I membrane and high p21ras protein expression. Thus, the oncogene-mediated
      downregulation of MHC class I surface expression resulted in a reduced CTL
      response. Attempts are in progress to revert the defects in MHC class I surface
      expression of oncogenic transformants by introducing the different elements of
      the antigen presentation pathway. Such studies will not only provide improved
      understanding of the mechanisms of tumor escape, but also will suggest strategies
      to repair cellular defects in cancer patients having impaired expression of MHC
      class I antigens.

PMID- 8862438
TI  - In vitro expansion of murine hematopoietic progenitor cells by leukemia
      inhibitory factor, stem cell factor, and interleukin-1 beta.
AB  - Murine hematopoietic progenitor cells were markedly expanded in the presence of
      leukemia inhibitory factor (LIF), interleukin (IL)-1 beta and/or stem cell factor
      (SCF), although SCF+IL-1 beta +IL-3, LIF+SCF+IL-3, and SCF+IL-1 beta showed an
      appreciable effect on the in vitro expansion of hematopoietic progenitor cells as
      well. In the presence of LIF+SCF+IL-1 beta, highly proliferative potential colony
      forming units (CFU-HPP) and colony forming units of mixed lineages (CFU-Mix) were
      more efficiently expanded than colony forming units granulocytes/macrophage (CFU
      GM) and burst-forming units of erythroid lineage (BFU-E) compared with the colony
      formations of freshly obtained bone marrow cells. The cell yield on day 5 in the
      presence of LIF+SCF+IL-1 beta was comparable to that in SCF+IL-1 beta and SCF+IL
      1 beta +IL-3. Nevertheless, colony formations were marked in LIF+SCF+IL-1 beta,
      thus suggesting that this combination can generate hematopoietic progenitor cells
      that possess greater potential for CFU-HPP, CFU-Mix, CFU-GM, and BFU-E colony
      formations. Hematopoietic cells expanded in the presence of LIF+SCF+IL-1 beta
      showed increased mRNA expressions of IL-1 beta, IL-3, IL-6, granulocyte colony
      stimulating factor (G-CSF), granulocyte/macrophage (GM)-CSF, interferon gamma
      (IFN-gamma), and LIF compared with those of nontreated hematopoietic cells.
      Furthermore, LIF+SCF+IL-1 beta induced increased IL-3 and GM-CSF mRNA expression
      in hematopoietic cells but induced decreased macrophage inflammatory protein 1
      alpha (MIP1 alpha) mRNA expression as compared with SCF+IL-1 beta +IL-3. These
      results suggest that the balance between stimulatory and inhibitory cytokines
      plays an important role in in vitro expansion of hematopoietic progenitor cells.

PMID- 8862439
TI  - Effects of recombinant human interleukin-11 (Neumega rhIL-11 growth factor) on
      megakaryocytopoiesis in human bone marrow.
AB  - We examined the effects of recombinant human interleukin 11 (rhIL-11) on in vivo
      human hematopoiesis. Twelve women with advanced breast cancer and no evidence of
      bone marrow (BM) involvement were treated with 10, 25, 50, or 75
      micrograms/kg/day of rhIL-11 administered subcutaneously for 14 consecutive days.
      Examination of bone marrow trephine biopsies obtained before and after rhIL-11
      treatment revealed unchanged BM cellularity at all doses, and a statistically
      significant increase in megakaryocyte (MK) frequencies (from 0.5 +/- 0.1% to 1.0
      +/- 0.3%) following administration of the two highest doses (p < 0.001). The BM
      biopsies also showed an increased proportion of immature myeloid and erythroid
      precursors following 14 days of treatment in all cases. The mean proportion of
      marrow cells stained with PC10, a monoclonal antibody (mAb) that recognizes the
      proliferating cell nuclear antigen (PCNA), increased from 16.3 +/- 5.7% to 45.8
      +/- 17.1% (p < 0.001) following the two highest treatment doses. Most of the
      PC10+ cells were promyelocytes and proerythroblasts. In this same group, the
      proportion of PC10+ MKs increased from 28.3 +/- 11.5% to 56.8 +/- 24.3% (p <
      0.01) after treatment, while megakaryocyte ploidy analysis revealed a greater
      number of higher ploidy (64N) megakaryocytes following rhIL-11 treatment (p <
      0.012). Numbers of BM and peripheral blood (PB) CD34+, CD34+DR+, and CD34+DR-
      cells did not change following rhIL-11 treatment. Following rhIL-11 therapy at
      the highest dose studied, a 3- and 10-fold increase in the number of committed BM
      MK progenitor cells (CFU-MK) was observed in two of three patients, while no
      change was seen in the number of the other BM or PB progenitor cells examined.
      rhIL-11 administration was also associated with an increase in BM reticulin
      content (fibrosis grade 1-2) in 7 patients. These results indicate that the
      administration of rhIL-11 to patients with normal hematopoiesis stimulates MK
      endoreduplication, PCNA expression, and, at high doses, increases MK and CFU-MK
      progenitor cell numbers. In addition, rhIL-11 was able to stimulate precursor
      cells of different marrow lineages without affecting the number of assayable
      progenitor cells.

PMID- 8862440
TI  - Combined effects of interleukin-3 and interleukin-11 on hematopoiesis in
      irradiated mice.
AB  - The survival rate and recovery of peripheral blood cells and platelets were
      studied in Balb/c mice subjected to different single doses of whole-body
      irradiation and treated with a combination of interleukin-3 (IL-3) and
      interleukin-11 (IL-11). In a first group of 20 mice, 7.5 Gy irradiation,
      immediately followed by 2 and 5 days therapy of IL-3 and IL-11, respectively,
      increased the survival rate to 82% compared to 20% in untreated controls. In a
      second group of mice irradiated with 7 Gy, we observed significantly higher
      platelet, white blood cell (WBC), and red blood cell (RBC) counts after treatment
      with both cytokines, as compared to IL-3 or IL-11 alone or untreated controls. In
      addition, the survival rate of the mice with the combined therapy was also
      increased to 84%, compared to 48% in untreated controls. Irradiation (8.5 Gy)
      gave 100% mortality for the control mice, and therapy with combined IL-3 plus IL
      11 had only a marginal effect. Interestingly, syngeneic bone marrow
      transplantation (BMT) alone, performed 16 hours after irradiation, increased the
      survival rate to 70%, while BMT combined with administration of IL-3 plus IL-11
      increased it to 97%. Furthermore, BMT combined with cytokine administration could
      partially prevent the severe WBC and RBC depletion observed in mice treated with
      BMT alone and promoted a more rapid recovery of platelets and RBC. These data
      show that the combination of IL-3 and IL-11 has a radioprotective effect and can
      enhance recovery of platelets, WBC, and RBC in irradiated mice. Combined IL-3
      plus IL-11 therapy may be clinically useful in myelodepression, especially in
      platelet depletion related to radiation therapy or chemotherapy, or after bone
      marrow transplantation.

PMID- 8862441
TI  - The influence of class II HLA type on the lymphoproliferative response of normal
      donors to a bcr-abl fusion peptide.
AB  - Chronic myelogenous leukemia (CML) is characterized by a t(9;22) chromosomal
      translocation resulting in the expression of a novel bcr-abl fusion protein. The
      region spanning the fusion point is novel to the immune system and hence
      represents a potential leukemia-specific antigen. The ability of a 21-mer b3a2
      fusion peptide to induce an in vitro lymphoproliferative response in a panel of
      54 normal donors has been tested. This gave a mean stimulation index of 2.73 (95%
      CI 2.42-3.05) and 50/54 (93%) of donors gave responses that were greater than
      those with bcr or abl control peptides. The mean stimulation index relative to
      that of the control peptides was 1.80 (95% CI 1.63-1.97; p < 0.001). Responses
      were optimal at concentrations ranging from 0.3-150 micrograms/mL and in most
      cases peaked at 9 days. There was no clear relationship between level of
      responsiveness to the b3a2 fusion peptide and the presence of any single HLA-A, 
      B, -DR, or -DQ allele. HIA-DRB1*0404 was the only allele that was not associated
      with responsiveness. It is therefore likely that the b3a2 fusion peptide can be
      presented to T cells during a primary immune response in the context of several
      different class II HLA allelic products, albeit at low efficiency. The
      implications for specific active immunotherapy of CML patients are discussed.

PMID- 8862442
TI  - Granulocyte-colony stimulating factor and stem cell factor are the crucial
      factors in long-term culture of human primitive hematopoietic cells supported by
      a murine stromal cell line.
AB  - The findings that murine marrow stromal cell line MS-5 supported the
      proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in
      long-term culture have been reported. In this study, we analyzed this
      proliferating activity of MS-5-conditioned medium (CM) on human primitive
      hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells
      were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7
      weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by
      using membrane filter (0.45 micron) was negligible for this activity. This
      indicated that the activity of MS-5 on human primitive hematopoietic cells is a
      soluble factor(s) secreted from MS-5, which is not induced by the contact between
      MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An
      active material with a molecular weight of about 150 kDa, determined by gel
      filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells
      and Mo7e, a human megakaryocytic cell line. This activity not only reacted with
      anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also
      neutralized in the presence of anti-mSCF antibody. Another active material with a
      molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth
      of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was
      inhibited in the presence of soluble mouse granulocyte-colony stimulating factor
      (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular
      domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the
      latter molecule supported the growth of the G-CSF dependent cell line FD/GR3,
      which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF
      receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the
      culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and
      rmG-CSF had synergistic activity on the growth of Lin-CD34+CD38- cells. These
      results indicated that the activity on Lin-CD34+CD38- cells included in MS-5-CM
      is based upon the synergistic effects of mSCF and mG-CSF.

PMID- 8862443
TI  - Internal autocrine regulation by erythropoietin of erythroleukemic cell
      proliferation.
AB  - Antisense oligomers (18 mers) corresponding to the erythropoietin and
      erythropoietin receptor 5' coding sequences cause marked suppression of
      proliferation of several lines of erythroleukemic cells. In these systems,
      phosphorothioate protected sense oligomers are inhibitory, while the unmodified
      sense oligomers have no significant effect on cell growth. These data indicate
      that proliferation of some erythroleukemic cells is under internal autocrine
      regulation by erythropoietin and its receptor.

PMID- 8862444
TI  - PAF and hematopoiesis. VIII. Biosynthesis and metabolism of PAF by human bone
      marrow stromal cells.
AB  - Human bone marrow stromal cells were studied for their ability to synthesize and
      to metabolize platelet-activating factor (PAF), a lipidic compound with potent
      immunoregulatory properties. When stimulated with 2 microM calcium ionophore for
      60 minutes, cultures of stromal cells increased their PAF production (3.52 +/-
      0.91 ng/1 x 10(6) cells) compared with controls (0.82 +/- 0.13 ng/1 x 10(6)
      cells). Addition of exogenous lyso PAF (100 nM) and acetyl-CoA (100 microM)
      during calcium ionophore stimulation did not change the PAF production. The
      synthesis of PAF was not influenced by the concentration of albumin in the
      incubation buffer. The PAF from stromal cells exhibited a hexadecyl chain at the
      sn-1 position of the molecule, as determined by reverse-phase HPLC. While stromal
      cells contained low amounts of PAF acetylhydrolase activity and did not secrete
      it in the culture medium, they metabolized exogenous PAF with 1-alkyl-2-acyl
      glycero-phosphocholine and neutral lipids as the major metabolic products. The
      present results are the first to demonstrate the synthesis and metabolism of PAF
      by human bone marrow stromal cells. These data suggest that they might be a
      source of the PAF found in the human bone marrow and/or might be important in the
      regulation of its levels. The role of PAF on the proliferation and functions of
      human hematopoietic cells deserves investigation.

PMID- 8862445
TI  - Restriction endonuclease in situ digestion (REISD): a novel quantitative sex
      independent method to analyze chimerism after bone marrow transplantation.
AB  - Restriction endonuclease (RE) in situ digestion (REISD) of human metaphase
      chromosomes and interphase nuclei may uncover cryptic polymorphisms. This
      technique can be applied to identify the individual origin of cells and thus
      analyze the hemopoietic chimerism that eventually results in leukemic patients
      after allogeneic bone marrow transplantation (BMT). In the current study, results
      of REISD with different REs are shown. In particular, the use of Sau 3A reveals a
      polymorphism for constitutive heterochromatin of chromosome 3 and may
      differentiate BMT donor (D) and recipient (R) cells. Once pre-BMT
      characterization shows a different Sau 3A digestion pattern of D and R cells, it
      is possible to monitor the development of hematopoietic cell populations in the R
      bone marrow after BMT. A panel of 24 patients who underwent BMT and their Ds were
      analyzed. The method presented here allowed cells from D and R to be
      distinguished, and therefore to quantify the post-BMT hemopoletic chimerism, in 6
      (25%) of the cases. This quantitative and sex-independent genetic approach to the
      study of hemopoietic chimerism has already shown itself to be useful in patients
      with leukemia who require a BMT, but could also be extended to other transplant
      situations.

PMID- 8862446
TI  - Forced expression of cytidine deaminase confers resistance to cytosine
      arabinoside and gemcitabine.
AB  - Genes that confer cellular resistance to cytotoxic agents have potential
      applications both for marrow protection following cancer chemotherapy and as
      dominant selectable markers for the selection of genetically modified
      hematopoietic cell populations in vivo. Cytidine analogues, including cytosine
      arabinoside (Ara-C), 2',2'-difluorodeoxycytidine (gemcitabine), and other drugs
      represent a clinically important class of chemotherapeutic agents for which no
      drug resistance gene has yet been described. Studies were performed to determine
      whether forced expression of a gene encoding the enzyme cytidine deaminase can
      confer resistance to cytosine arabinoside (Ara-C) and gemcitabine in vitro. A
      pooled population of NIH3T3 cells overexpressing cytidine deaminase from a
      retroviral construct based on the LXSN-vector (LCDSN) demonstrated a 4.5-fold
      increased resistance to Ara-C based on the 50% inhibitory concentration (ID50)
      and a 3.7-fold increased resistance to Ara-C based on the 80% inhibitory
      concentration (ID80) relative to cells transduced with a control vector. In the
      hemopoietic cell line CCRF-CEM, the same retroviral construct conferred a 2.1
      fold increased resistance to Ara-C by ID50 and a 3.0-fold increased resistance to
      Ara-C by ID80 relative to cells transduced with a control vector. CEM cells
      transduced with LCDSN were also resistant to gemcitabine (2.4-fold by ID50 and
      2.5-fold by ID80). Furthermore, Ara-C-resistance could be completely reversed in
      LCDSN-transduced CEM cells by a specific inhibitor of cytidine deaminase,
      tetrahydrouridine (THU). Expression of the transgene was confirmed by RNase
      protection assay and by an enzyme activity assay. These results provide the first
      direct evidence that forced expression of cytidine deaminase confers cellular
      resistance to Ara-C and gemcitabine.

PMID- 8862447
TI  - High-resolution cell cycle analysis of defined phenotypic subsets within
      primitive human hematopoietic cell populations.
AB  - We have developed a novel protocol for analysis of cell cycle status within
      specific subsets of primitive human hematopoietic cells. The technique, referred
      to as SID (surface, intracellular, and DNA) analysis, allows for the simultaneous
      characterization of cell surface and intracellular antigens, as well as
      quantitation of DNA content. To evaluate the technique, early human hematopoietic
      cells were examined using surface staining for the CD34 and CD38 antigens to
      identify primitive cells. Relative cell cycle status within defined phenotypic
      subsets (CD34+ and CD34+/CD38-) was determined by simultaneous two-parameter
      analysis using DNA content vs. antibody staining for the Ki-67 antigen. Ki-67 is
      not expressed in quiescent cells, but is quickly up-regulated as cells are
      induced to cycle. Consequently, expression of Ki-67, in combination with DNA
      content can be used to delineate all phases of the cell cycle (G0, G1, S, and
      GZ/M). We demonstrate that cycle induction of CD34+ cells, using IL-3, IL-6, and
      stem cell factor (SCF), does not correlate with activation of the CD34+CD38-
      subpopulation during ex vivo culture. Rather, CD34+/CD38- cells are much more
      refractory to cycle activation, requiring at least 72 hours to show significant
      levels of induction. In addition, primitive cells derived from bone marrow (BM)
      vs. mobilized peripheral blood (PB) show differing degrees of responsiveness to
      conventional ex vivo culture conditions. Finally, the effect of IL-3, IL-6, SCF,
      and Flt3 ligand (FL) on cycle induction was examined. It was observed that IL-3
      synergized strongly with IL6+SCF to activate quiescent CD34+/CD38- cells.
      Moreover, when FL was combined with IL-3+IL-6+SCF, there was a small but
      reproducible increase in activation of CD34+/CD38- cells from G0 to G1. These
      data suggest that ex vivo behavior of primitive human stem cell populations is
      amenable to comprehensive flow cytometric analysis, and that such studies can
      provide detailed information on the biological response of stem cells to ex vivo
      culture and manipulation.

PMID- 8862448
TI  - Induction and persistence of cytogenetic damage in mouse splenocytes following
      whole-body X-irradiation analysed by fluorescence in situ hybridization. II.
      Micronuclei.
AB  - Micronuclei are formed during cell division either from lagging acentric
      fragments caused by chromosomal breakage or from whole chromosomes. Female Swiss
      mice were used to study the induction and persistence of micronuclei (MN) in
      isolated splenocytes up to 112 days after 2Gy whole-body X-irradiation.
      Micronucleus frequency in cytokinesis blocked binucleated cells was estimated
      using acridine orange staining. Fluorescence in situ hybridization (FISH) with
      murine minor satellite DNA probe was used to detect aneuploidy (MN with a
      centromere). The initial frequency of micronuclei immediately after X-ray
      exposure was found to be 39.6 per 100 cells. The MN frequency declined in an
      exponential manner during the subsequent period and at day 14, reached about half
      the value observed immediately after irradiation with a further 50% reduction by
      day 28 and only 3% MN could be detected at day 112 post-irradiation. Some
      induction of aneuploidy was observed after X-irradiation, deduced in the form of
      centromere-positive micronuclei (C + MN) as detected by the presence of a minor
      satellite signal after FISH. Of MN, 23% were centromere-positive in the first
      fixation time after X-ray exposure. Some of the MN showed two or more centromeric
      signals. The percent C + MN increased gradually until day 7 post-exposure. At day
      14, this value started to decline, reaching 13% by 112 days post-irradiation.
      FISH with a biotinylated minor satellite probe can reliably be used in the
      cytokinesis blocked micronucleus assay to distinguish the clastogenic and/or
      aneugenic activity of a test chemical or physical agent.

PMID- 8862449
TI  - Chromosome analysis by fluorescence in situ hybridization: further indications
      for a non-DNA-proportional involvement of single chromosomes in radiation-induced
      structural aberrations.
AB  - The frequencies of symmetrical complete and incomplete translocations and
      dicentrics induced in human lymphocytes after in vitro irradiation with 3Gy X
      rays were analysed by the use of fluorescence in situ hybridization (FISH).
      Single whole chromosome painting (WCP) probes, specific for chromosomes 1-4, 6
      10, 12, 14 and X were hybridized separately. A human pancentromeric DNA-probe was
      used simultaneously for unequivocal centromere detection. For both aberration
      types, symmetrical translocations and dicentrics, a significant deviation from a
      DNA-proportional distribution was found. In general, chromosomes with a higher
      DNA content (chromosomes 1-3, 6 and 7) were less frequently involved in the
      formation of symmetrical translocations and dicentrics than expected according to
      their DNA-content, whereas smaller chromosomes were more frequently involved. The
      only exception was chromosome 4, exhibiting the highest translocation frequency
      of all chromosomes analysed. Ratios of the yields of symmetrical translocations
      to the yields of dicentrics varied between 0.9 and 1.8 for the single
      chromosomes. The present results substantiate our previous data obtained with
      identical chromosomes but examined in four different triple combinations.

PMID- 8862450
TI  - Chromosome painting of radiation-induced micronuclei.
AB  - In this report, in situ hybridization with whole chromosome painting probes was
      used to paint radiation-induced micronuclei (MN) in three lymphoblastoid cells
      lines to investigate the frequency of radiation-induced MN. The results obtained
      for four different chromosomes showed that there was a significant deviation of
      the numbers of signal-positive MN from that expected on the basis of DNA
      proportionality. Restriction of the analysis to three chromosomes showed that the
      deviations arose primarily from chromosome 7, which was underrepresented in the
      numbers of signal-positive MN in the group of chromosomes studied.

PMID- 8862451
TI  - Radiation-induced chromosome damage in astronauts' lymphocytes.
AB  - The increased number of manned space missions has made it important to estimate
      the biological risks encountered by astronauts. As they are exposed to cosmic
      rays, especially ions with high linear energy transfer (LET), it is necessary to
      estimate the doses they receive. The most sensitive biological dosimetry used is
      based on the quantification of radiation-induced chromosome damage to human
      lymphocytes. After the space missions ANTARES (1992) and ALTAIR (1993), we
      performed cytogenetic analysis of blood samples from seven astronauts who had
      spent from 2 weeks to 6 months in space. After 2 or 3 weeks, the X-ray equivalent
      dose was found to be below the cytogenetic detection level of 20 mGy. After 6
      months, the biological dose greatly varied among the astronauts, from 95 to 455
      mGy equivalent dose. These doses are in the same range as those estimated by
      physical dosimetry (90 mGy absorbed dose and 180 mSv equivalent dose). Some blood
      cells exhibited the same cytogenetic pattern as the 'rogue cells' occasionally
      observed in controls, but with a higher frequency. We suggest that rogue cells
      might result from irradiation with high-LET particles of cosmic origin. However,
      the responsibility of such cells for the long-term effects of cosmic irradiation
      remains unknown and must be investigated.

PMID- 8862452
TI  - Rejoining of DNA double-strand breaks induced by accelerated nitrogen ions.
AB  - Rejoining of radiation-induced DNA double-strand breaks (dsb) was measured in
      cultured cells with pulsed-field gel electrophoresis after radiation doses in the
      range of 5-30 Gy. Human glioma, U-343MG and Chinese hamster, V79, cells were
      irradiated with either accelerated nitrogen ions of high linear energy transfer,
      LET approximately 125 keV/ microns, or photons from 60Co. The induction
      frequencies of dsb were similar for the two radiation qualities with a relative
      biological effectiveness, RBE, of 0.90 and 0.89 for the human and hamster cell
      lines respectively. The biphasic rejoining kinetics differed significantly
      between the two radiation qualities when studied in the human glioma cells. The
      difference was seen within the first hour after irradiation and after 6 h there
      were considerable differences in both the total amount of unrejoined dsb and the
      fraction of dsb rejoined during the slow phase. When rejoining was analysed 20-22
      h after irradiation, the nitrogen ions gave 2.5-2.9 times more residual dsb than
      the gamma photons. The results for the hamster V79 cells were, up to 2h after
      irradiation, similar, but the difference between the two radiation qualities was
      less accentuated. In summary, similar initial yields of dsb after exposure of
      cells to high or low LET resulted in both radiation quality and cell type
      dependent differences when the rejoining of these breaks were compared.

PMID- 8862453
TI  - DNA double- and single-strand breaks induced by accelerated He2+ and N6+ ions in
      human cells: relative biological effectiveness is dependent on the relative
      contribution of the direct and indirect effects.
AB  - Double (dsb) and single-(ssb) strand breaks induced by accelerated He2+ ions (LET
      from 10 to 220 keV/micron with > 70% in the range of 35-55 keV/micron, mean LET
      about 40 keV/micron) and N6+ ions (LET 125 keV/micron) have been determined in
      three DNA substrates derived from human cells in culture. He ions were 50% more
      efficient than N ions to induce dsb in intact cells. In the presence of a high
      concentration of an OH-radical scavenger, dimethylsulphoxide (DMSO), the dsb were
      reduced by a factor of 4.5 after He ions but only a factor of 1.4 after N ions,
      i.e. N ions were about a factor of three more efficient in a substrate where
      direct hits in the DNA dominated. With gamma rays DMSO gives a reduction by a
      factor of 3.6. In nucleoids, where the histones were removed by salt treatment,
      dsb induction increased 22, 18 and 12 times for gamma rays, He ions and N ions
      respectively. Under these conditions dsb is about 1.5-fold higher after He
      compared with N ions. Total number of breaks, ssb and dsb, were determined for
      intact cells. Compared with gamma-rays the breaks were reduced by a factor of 4
      after He ions and a factor of 14 after N ions, i.e. ssb and dsb seem to be in the
      same range after nitrogen ions. Although our measurements do not allow an
      absolute determination of relative biological effectiveness (RBE) for He and N
      ions induced dsb, we can show that the RBE for N ions increases by a factor of
      2.5 if OH radicals are removed, and decreases by a factor of 2 if most of the
      protection against OH radicals is removed, altogether a variation of a factor of
      5. RBE for He ions, on the other hand, is almost independent of irradiation
      conditions.

PMID- 8862454
TI  - Response of V79 cells to low doses of X-rays and negative pi-mesons: clonogenic
      survival and DNA strand breaks.
AB  - Mammalian cells are hypersensitive to very low doses of X-rays (< 0.2 Gy), a
      response which is followed by increased radioresistance up to 1 Gy. Increased
      radioresistance is postulated to be a response to DNA damage, possibly single
      strand breaks, and it appears to be a characteristic of low linear energy
      transfer (LET) radiation. Here we demonstrate a correspondence between the extent
      of the increased radioresistance and linear energy transfer of 250 kVp X-rays and
      plateau and Bragg peak negative pi-mesons. The results support our hypothesis
      since the size of the increased radioresistant response appears to correspond to
      the number of radiation induced single-strand breaks. Furthermore, since survival
      prior to the increased radioresistant response (< 0.2 Gy) was LET-independent,
      these data support the notion that the increased radioresistant response may
      dictate the overall survival response to higher doses. However, while these data
      provide further circumstantial evidence for the involvement of DNA strand breaks
      in the triggering of increased radioresistance, more direct conclusions cannot be
      made. The data are not accurate enough to detect structure in the single-strand
      break profiles, the production of single-strand breaks being apparently linear
      with dose.

PMID- 8862455
TI  - Single- and double-strand breaks in pBR322 plasmid DNA by monochromatic X-rays on
      and off the K-absorption peak of phosphorus.
AB  - Using a synchrotron irradiation system pBR322 plasmid DNA was irradiated under
      vacuum by monochromatic X-rays having five specific photon energies (2.147,
      2.153, 2.159, 2.168 and 2.199 keV) both on and off the K-absorption peak (2.153
      keV) of phosphorus. The single- and double-strand breaks (ssb and dsb) were
      measured as conversions of the closed circular form of DNA (form I) to open
      circular (form II) and linear (form III) forms respectively. Exposures to induce
      one strand break per molecule were lowest at the peak (2.153 keV), and highest at
      2.147 keV; the ratios were 2.7 for ssb and 3.0 for dsb. The exposures for dsb
      were 21-26 times higher than those for ssb. When the exposures were converted to
      absorbed doses in grays the absorbed doses per ssb were almost independent of
      photon energy. This result indicates that a certain absorbed dose was necessary
      to induce a ssb, regardless of whether photons were absorbed by the K-shell of
      phosphorus or by other shells, or by other atoms. However, the absorbed dose per
      dsb at 2.147 keV was 1.17 times higher than that averaged over four X-ray
      energies above 2-153 keV, indicating that the K-shell absorption, and the
      subsequent Auger event, efficiently induce dsb. The results are also discussed
      concerning the number of photo-absorptions of the constituent atoms per DNA
      strand break.

PMID- 8862456
TI  - Interpretation of inverse dose-rate effects for mutagenesis by sparsely ionizing
      radiation.
AB  - An inverse dose-rate effect has sometimes been observed for mutagenesis in cells
      exposed to gamma-rays. We model such data quantitatively with the key assumption
      that the effect is caused in cycling cells by correlated variations in
      sensitivity across the cell cycle, for both mutation and killing. We quantify
      this approach using the LQR (linear-quadratic + resensitization) formalism, which
      describes the response to radiation of a heterogeneous cell population. This
      model is applied to an exponentially growing population. We compare its
      predictions with dose- and dose-rate dependent mutation data and show that it can
      well fit the observed inverse dose-rate effect, as well as providing an
      explanation of why inverse dose-rate effects have been seen in some experiments,
      but not in others. The actual values of the model parameters emerging from the
      analysis are reasonable in magnitude, based on their biological interpretations.
      We conclude that the LQR model can quantify cell-cycle redistribution effects
      without overparameterization, and that the data favour a correlation explanation
      of inverse dose-rate effects for mutagenesis by low-LET radiation. It is less
      clear that this explanation is appropriate to high-LET radiation-induced
      oncogenic transformation, although all potential explanations of inverse dose
      rate effects predict that, at appropriately low doses, no dose-rate effects of
      any kind are expected.

PMID- 8862457
TI  - Mutations induced by gamma-irradiation of M13 bacteriophages containing single
      stranded DNA.
AB  - Oxygenated suspensions of M13 bacteriophages, containing single-stranded M13mp10
      DNA, were gamma-irradiated followed by infection of E. coli cells. Mutants in the
      mutational target sequence, which consists of the lac promoter /operator region,
      the lacZ alpha gene, and a 144 bp inframe insert in the lacZ alpha gene, were
      selected and characterized. Except for three one-base deletions, all of the 51
      mutations characterized were base substitutions. All base substitutions appeared
      to involve guanines and cytosines and none affect adenines and thymines. Since
      most of the known repair systems do not act on single-stranded DNA, the
      conclusion can be drawn that radiation induces under these conditions only
      mutagenic damages on guanine and cytosine. Although all possible G- and C
      transversions and transitions were found, there is a strong preference for G-->C
      and G-->T transversions (21 and 25% of all base substitutions, respectively) and
      C-->T transitions (48% of all base substitutions). These results indicate, that
      the G/C-->C/G and G/C-->T/A transversions, found after irradiation of double
      stranded M13 DNA, are mainly due to radiation guanine products, whereas cytosine
      damage is mainly responsible for G/C-->A/T transitions.

PMID- 8862458
TI  - Transferrin-mediated uptake of plutonium by spermatogenic tubules.
AB  - Using isolated rat seminiferous tubules as an in vitro model, we have found that
      238Pu can cross the blood-tubule barrier and accumulate within tubules in a time
      dependent manner. Furthermore, similar to 59Fe, tubule 238Pu uptake was inhibited
      by the addition of excess transferrin, suggesting that plutonium may utilize the
      physiological iron-transferrin pathway to cross the blood-tubule barrier. However
      unlike 59Fe, 238Pu was only transiently associated with the tubules, suggesting
      differences in the intracellular processing of these radionuclides. The
      assumptions made in the estimation of doses to the human testis from incorporated
      plutonium are considered.

PMID- 8862459
TI  - Radiation-induced translocation of protein kinase C through membrane lipid
      peroxidation in primary cultured rat hepatocytes.
AB  - A mechanism of radiation-induced activation of protein kinase C was investigated
      in primary cultured rat hepatocytes. Irradiation of hepatocytes with 5 Gy or 50
      Gy of gamma-rays caused an immediate and transient increase in the activity of
      protein kinase C in the membrane fraction, and a decrease in this activity in the
      cytosol fraction. A ligand binding procedure for protein kinase C using [3H]PDBu
      demonstrated that PDBu binding content increased in the membrane fraction and
      decreased in the cytosol fraction following irradiation. These results suggest
      that protein kinase C molecules were translocated from cytosol to the membrane
      after irradiation of the hepatocytes. Irradiation also induced lipid peroxidation
      of hepatocytes in the range from 0 to 50 Gy in a radiation dose-dependent
      fashion. This induction of lipid peroxidation was markedly suppressed by the
      addition of Trolox, a radical scavenger. Treatment of hepatocytes with Trolox
      also caused simultaneous inhibition of the radiation-induced increase in the PDBu
      binding content of the membrane fraction. We conclude that radiation-induced
      activation of protein kinase C results from the translocation of protein kinase C
      from cytosol to membrane due to membrane lipid peroxidation through reactive
      oxygen species produced by radiation.

PMID- 8862460
TI  - Influence of heat on Na(+)-dependent HCO3-/Cl- exchanger function in a
      thermoresistant cell line.
AB  - During previous studies on the relationship between thermosensitivity and
      intracellular pH (pHi) regulation in mammalian cells, we observed that the
      thermoresistant TR-4 cells appeared to be resistant to manipulations of the
      Na+/H+ antiport, one of the two primary membrane regulators of pHi. We
      hypothesized that this might be due to up-regulation of the alternate pHi
      regulator, the Na(+)-dependent HCO3-/Cl- exchanger, in the TR-4 cells. We have
      now evaluated the effect of heat exposure on the function of the Na(+)-dependent
      HCO3-/Cl- exchanger in both the parent RIF-1 and the thermoresistant variant TR-4
      cells. We also assessed thermosensitivity of the cell lines under conditions of
      either pHe 7.2 or 6.8, with NaHCO3, with or without the addition of DIDS, an
      inhibitor of HCO3-/Cl- exchanger function. After 2h of heating at 43 degrees C,
      relative exchanger function declined to around 50% for the TR-4 cells and 10% for
      the RIF-1 cells. DIDS (0.2 mM) enhanced thermal cytotoxicity in both cells lines,
      by around 1 log when the cells were heated at neutral conditions, and by around
      1.5 log when the condition became acidic. Results from pHi measurements during
      heating reflected the clonogenic survival data in that lower pHi levels were
      associated with the conditions when DIDS was present. We conclude that in the TR
      4 cells, the Na(+)-dependent HCO3-/Cl- exchanger appears to be a more important
      regulator of pHi than the Na+/H+ antiport.

PMID- 8862461
TI  - Influence of sleep state and respiratory pattern on cyclical fluctuations of
      cerebral blood flow velocity in healthy preterm infants.
AB  - To examine the influence of sleep state, respiratory pattern, and ventilation on
      cyclical fluctuations (CF) in cerebral blood flow (CBF) velocity (CBFV), we
      studied 21 'healthy' preterm infants: birth weight 1,790 +/- 162 g (SEM), study
      weight 1,960 +/- 165 g, gestational age 32 +/- 1 weeks, postnatal age 20 +/- 4
      (range 8-57) days. The CBFV was measured using on-line pulsed Doppler ultrasound
      by insonating the middle cerebral artery. Breathing was measured using a flow
      through system. The sleep state was monitored according to conventional criteria.
      Three hundred and seventy-five epochs of 1 min each were analyzed; 207 during
      quiet sleep (QS) and 168 during rapid eye movement (REM) sleep. CFs in CBFV were
      detected in all babies. The frequency of CF ranged from 0.5 to 6 cycles/min. The
      proportion of epochs showing CF was similar during both sleep states (56% QS vs.
      59% REM; p = NS). Although the mean CBFV (cm/s) was similar in these two sleep
      states, the mean coefficient of variation, a measure of CF amplitude, was
      significantly higher during REM as compared with QS (6 +/- 0.5 vs. 4.3 +/- 0.2%;
      p < 0.05). Similarly, the mean CBFVs were similar with various respiratory
      patterns, but the coefficient of variation was significantly higher in periodic
      and apneic patterns as compared with regular and irregular respiratory patterns
      (5.6 +/- 0.6% periodic, 5.6 +/- 0.3% apneic, 3.6 +/- 0.3% regular, and 4.1 +/-
      0.5% irregular, p < 0.05). The amplitude of CF was associated with the
      variability of the heart rate (p < 0.05), but not with the variability of the
      respiratory measurements. These findings suggest: (1) REM sleep is associated
      with a greater CBF variability than QS, and (2) periodic and apneic breathing are
      associated with a greater CBF variability than regular or irregular breathing. We
      speculate that sleep state and respiratory pattern do not determine but modulate
      the CBF. Our data suggest that in studies involving interpretation of CBFV data
      using the Doppler technique, breathing patterns should be taken into account in
      addition to sleep state.

PMID- 8862463
TI  - Human colostrum stimulates cytokine production.
AB  - The effect of human colostrum on the production of IL-1, IL-3 and IL-6 by
      peripheral blood mononuclear cells (PBMCs) has been investigated. The aqueous
      phase of human colostrum significantly stimulated the production of these three
      cytokines. These findings show the importance of breast feeding not only as a
      well-balanced nutrient supply but also as a source for growth-promoting factors.
      It is suggested that the enhanced secretion of IL-1, IL-3 and IL-6 induced by
      human colostrum may compensate for the lower capacity of neonatal PBMCs to
      produce these cytokines. It is also possible that, by stimulating the secretion
      of these cytokines, breast feeding may provide an additional mechanism for the
      regulation of the neonatal immune system and hematopoiesis.

PMID- 8862462
TI  - Cord blood neutrophil responses to polyunsaturated fatty acids: effects on
      degranulation and oxidative respiratory burst.
AB  - Lipid mediators such as arachidonic acid (AA) generated during inflammation play
      an important role in stimulating phagocytic cell responses. Since cord blood
      neutrophils show reduced responses to agonists such as the bacterial tripeptide f
      Met-Leu-Phe (fMLP), it would be of interest to know whether cord blood
      neutrophils show normal or reduced responses to AA and other fatty acids. The
      data showed that the polyunsaturated n-6 fatty acid (PUFA) AA stimulated cord
      blood neutrophils to produce a respiratory response (measured by
      chemiluminescence) and degranulation. Other PUFAs, eicosapentanoic acid and
      docosahexaenoic acid, elicited similar responses in cord blood neutrophils.
      Specific granule release and chemiluminescence response in cord blood neutrophils
      were evident at 0.1-0.5 microgram/ml of PUFA, concentrations normally found in
      vivo during inflammation or following diets enriched with n-3 fatty acids.
      Neutrophil responses to PUFA were significantly better than those to either fMLP
      or phorbol myristate acetate. Cord blood neutrophils primed with PUFA showed
      enhanced responses to fMLP. These results suggest that cord blood neutrophils
      respond to a similar degree to adult neutrophils to the AA which is generated
      during the inflammatory response and to the n-3 fatty acids eicosapentaenoic
      acid/docosahexaenoic acid, both of which may be used in diet manipulation of
      neurological function and immunological reactions.

PMID- 8862464
TI  - Prenatal hypoxia alters the postnatal development of beta-adrenoceptors in the
      rat myocardium.
AB  - The effect of prenatal hypoxia on the development of the beta-adrenoceptor during
      the ontogenesis of rats was investigated. It was shown that the offspring from
      hypoxic dams, in comparison with normoxic control animals, exhibited alterations
      of the density (Bmax) of the myocardial beta-receptors and of the catecholamine
      levels in heart tissue during development. The results suggest that the beta
      adrenoceptor changes might be involved in the phenomenon of enhanced sensitivity
      of prenatal hypoxic animals to catecholamines in adult age.

PMID- 8862465
TI  - Nitric oxide modulates glomerular filtration and renal blood flow of the newborn
      rabbit.
AB  - The current study was performed in 17 anesthetized and mechanically ventilated
      newborn rabbits to investigate the role of nitric oxide (NO) in the regulation of
      basal renal function of the immature kidney. Renal blood flow and glomerular
      filtration rate were determined by the clearance of p-aminohippuric acid and
      inulin, respectively. In 9 newborn rabbits (group 1), L-NAME, a NO synthesis
      inhibitor, significantly increased the renal vascular resistance by 31 +/- 9% and
      decreased the renal blood flow by 20 +/- 6%. The fraction of filtration
      significantly increased by 8 +/- 5% despite a delayed decline in glomerular
      filtration rate by 13 +/- 5%. Mean arterial pressure and heart rate were not
      altered. In 8 additional newborn rabbits (group 2), L-arginine, the physiological
      precursor of NO synthesis, partially reversed the renal hemodynamic changes
      induced by L-NAME. The present results demonstrate that the decrease in NO
      production induced by L-NAME (1) significantly affects the renal microcirculation
      of the immature newborn rabbit kidney and (2) predominantly increases the
      postglomerular renal vascular resistance. Endogenous NO thus appears to play a
      major role in maintaining the basal perfusion of the immature kidney.

PMID- 8862466
TI  - Effects of preweaning sensorimotor stimulation on behavioral and neuronal
      development in motor and visual cortex of the rat.
AB  - The present study investigates the effects of early sensorimotor stimulation on
      behavioral and neuronal cytodifferentiation in motor and visual cortex of
      lactating rats. Seventy-two male and female Sprague-Dawley albino rats were
      systematically submitted to environmental stimulation during the early postnatal
      period (postnatal days 5-21). On postnatal day 22, four behavioral tests were
      performed (open field, narrow path crossing, hind limb support and ascending on a
      rope). In order to evaluate dynamic neuronal changes induced by sensorimotor
      enrichment, brains were stained through the Golgi-Cox-Sholl method. Morphometric
      studies were carried out in pyramidal neurons located in motor and visual
      cortical layers II and III, by measuring their basal dendritic length and
      branching. Further, wide cortical field studies were performed with the aim of
      evaluating the degree of development reached by clusters of pyramidal cells. The
      results indicate that sensorimotor stimulation carried out during the suckling
      period produced a significant increase in neuronal cytodifferentiation as
      observed in single cell studies. However, collective neuronal evaluations yielded
      less significant results. Consistently, rats exposed to enriched environments
      showed a better performance in behavioral adaptive responses.

PMID- 8862467
TI  - Moderate anticonvulsant action of baclofen does not change during development.
AB  - The possible anticonvulsant action of baclofen, a GABAB (gamma-aminobutyric acid)
      receptor agonist, was studied using two types of motor seizures (minimal, clonic
      and generalized tonicoclonic) elicited by pentylenetetrazol in adult rats and rat
      pups, 7, 12, 18, and 25 days old. If baclofen was administered intraperitoneally
      (only in 12- and 25-day-old rats), no effect could be observed in 25-day-old
      animals. In 12-day-old rats, only the 12-mg/kg dose led to a prolongation of the
      generalized tonicoclonic seizure latency. Subcutaneous administration of baclofen
      (3, 6, or 12 mg/kg 30 min before subcutaneous pentylenetetrazol injection) led to
      a moderate action against the tonic phase of generalized tonicoclonic seizures:
      the tonic phase of hind limbs was significantly suppressed in all age groups,
      whereas total suppression of the tonic phase was only outlined. Minimal, i.e.,
      clonic, seizures with preserved righting ability were not influenced by baclofen.
      The conclusion could be made that the anticonvulsant action of baclofen is
      dependent on the model of seizures used and that there is no change of baclofen
      action against pentylenetetrazol-induced seizures during postnatal development in
      rats.

PMID- 8862468
TI  - Catalytic properties and stability of lipase purified from human pancreatic
      juice.
AB  - Catalytic properties of a preparation of human pancreatic lipase purified from
      pancreatic juice have been compared to those of the enzyme present in pooled
      plasma from patients suffering from acute pancreatitis. They were very similar as
      regards influence of effectors (sodium deoxycholate, colipase and Ca2+), optimal
      pH and apparent KM in optimized conditions. The stability of the preparation
      appeared to be satisfactory. It was found to be stable for at least 200 days in a
      liquid form at +4 degrees C and predictive degradation rates per year of the
      lyophilized form at +4 degrees C and -20 degrees C were 0.06% and 0.00%,
      respectively. The close similarity of properties of this preparation with those
      of a recombinant human pancreatic lipase produced in V79 Chinese hamster lung
      cells suggests that both approaches (purification from human pancreatic juice and
      gene transfer technology) could be used to produce a suitable reference material
      for this enzyme.

PMID- 8862469
TI  - Cholesterol metabolism in cells with different peroxisomal defects.
AB  - We showed previously that cholesterol biosynthesis in dermal fibroblasts from
      patients with metabolic disorders of peroxisomal origin is increased in steps
      prior to mevalonate, whereas low-density-lipoprotein(LDL)-receptor activities
      were not different from control fibroblasts. Here, the suppression of 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase activity by lovastatin was studied
      both in dermal fibroblasts from patients with different peroxisomal defects and
      in a Chinese hamster ovary (CHO) cell line lacking morphologically intact
      peroxisomes. In addition, the formation of intracellular cholesteryl esters (a
      measure of acyl-CoA:cholesterol acyltransferase(ACAT)-activity) stimulated by
      exogenous LDL was investigated. A dose-dependent suppression of cholesterol
      biosynthesis by lovastatin at concentrations of 1-50 mumol/l was observed which
      was comparable in normal and peroxisomal-disease fibroblasts. ACAT activity was
      measured in the absence and presence of exogenous LDL using [3H]oleate as a
      substrate for cholesterol ester synthesis. The basal esterification rate was
      equal or lower in peroxisomal-defective fibroblasts compared with controls. In
      the presence of exogenous LDL, cholesterol esterification was significantly
      impaired in all defective cells in comparison with normal fibroblasts. We
      conclude that changes in cholesterol homeostasis in peroxisomal diseased
      fibroblasts be related to cholesterol ester formation.

PMID- 8862470
TI  - Production and certification of an enzyme reference material for pancreatic alpha
      amylase (CRM 476).
AB  - We describe the preparation of a lyophilized material containing purified human
      pancreatic alpha-amylase and the certification of its catalytic concentration.
      The enzyme was purified from human pancreas by ammonium sulphate precipitation
      and chromatography successively on DEAE-Sephacel, CM-Sepharose and Sephadex G-75.
      The purified enzyme had a specific activity of 52.9 kU/g protein and was > 99%
      pure on polyacrylamide gel electrophoresis. Only trace amounts of lipase and
      lactate dehydrogenase were detected in the purified fraction. The purified
      pancreatic alpha-amylase had a molar mass of 57,500 g/mol and an isoelectric
      point at 7.1. The material was prepared by diluting the purified alpha-amylase in
      a matrix containing PIPES buffer 25 mmol/l, pH 7.0, sodium chloride 50 mmol/l,
      calcium chloride 1.5 mmol/l, EDTA 0.5 mmol/l and human serum albumin 30 g/l,
      dispensing in ampoules and freeze-drying. The ampoules were homogeneous and the
      yearly loss of activity on the basis of accelerated degradation studies was less
      than 0.01% at -20 degrees C. The certified value for alpha-amylase catalytic
      concentration in the reconstituted reference material is 555 U/l +/- 11 U/l when
      measured by the specified method at 37 degrees C. The material can be used to
      verify the comparability of results from laboratories, for intra-laboratory
      quality control or for calibration of alpha-amylase catalytic concentration
      measurements.

PMID- 8862471
TI  - Neuraminidase assay in cultured human fibroblasts: in situ versus in vitro
      procedures.
AB  - Further investigations have been carried out to characterize a published
      procedure of neuraminidase assay, in which the activity is measured directly on
      the cell culture layer. The pH optimum was 4.0. A Vmax value of 130 nmol/mg/h and
      a K(m) of 0.3 mmol/l were found. During incubation in the acid buffer,
      arylsulphatase activity was released into the medium, whereas neuraminidase
      activity remained attached to the cells. The in situ method allowed an
      unequivocal diagnosis of primary and secondary neuraminidase deficiencies.
      Because of its simplicity and reliability, the method appears useful as a routine
      method in clinical laboratories.

PMID- 8862472
TI  - Hepatic levels of bile acids in end-stage chronic cholestatic liver disease.
AB  - In chronic cholestatic liver disease hydrophobic and potentially cytotoxic bile
      acids are assumed to accumulate in the liver. To test this hypothesis we
      investigated bile acid levels and pattern in livers and serum of patients with,
      (A) end-stage chronic cholestatic liver disease, and with (B) end-stage cirrhosis
      of alcoholic/chronic hepatitic origin who underwent liver transplantation. Bile
      acids were also analyzed in (C) normal liver tissue. Levels of bile acids were
      215 +/- 39.1 nmol/g liver (wet weight) in chronic cholestasis and 120 +/- 32.7
      and 56.1 +/- 24.2 nmol/g liver in group B and group C (P < 0.01 and P < 0.005),
      respectively. Cholic acid was the prevailing bile acid in chronic cholestasis
      (51%) and was elevated eight-fold as compared to group C (P < 0.005).
      Chenodeoxycholic acid contributed 41% to total bile acids and was elevated four
      fold (P < 0.005). Deoxycholic acid contributed only 1.5% to bile acids in chronic
      cholestasis as compared to 27% in group C (P < 0.01) and was absent in group B.
      Levels of lithocholic acid tended to be increased in chronic cholestasis as
      compared to group C and its sulfation was impaired (P < 0.05). The pattern of
      serum bile acids in chronic cholestasis agreed well with the bile acid pattern in
      the explanted livers. We conclude that hepatic accumulation of hydrophobic
      chenodeoxycholic acid and impaired sulfation of lithocholic acid might contribute
      to tissue degeneration in chronic cholestatic liver disease due to the detergent
      effects of these bile acids.

PMID- 8862473
TI  - Use of an enzyme thermistor for semi-continuous blood glucose measurements.
AB  - A method to monitor glucose in whole blood is presented. The aim of the project
      was to develop a prototype for a bedside monitor system for semi-continuous
      monitoring of the blood glucose concentration, requiring only one calibration.
      This was made possible by using the special advantage of the thermal sensor
      technique in combination with the adjustment of flow. The glucose concentration
      was determined from the difference between the sensor response and an estimated
      background signal. Using standard addition technique, calibration factors for
      background and sensitivity were set and remained unchanged during the monitoring.
      The background signal was 45 +/- 8 mV (mean +/- S.D., n = 8) and the sensitivity
      was 28 +/- 1 mV/mmol (mean +/- S.D., n = 4). Recovery in whole blood was 90-98%
      (mean 94%, n = 12). With an injection interval of 3 min the precision with the
      sensor was < 3% over more than 100 blood samples. Response time was about 60 s.
      The calculated glucose values correlated, r = 0.98, with the values obtained with
      an YSI glucose analyser (Yellow Springs Instruments. Yellow Springs, OH, USA),
      over the range 2-20 mmol/l.

PMID- 8862474
TI  - Kinetic differences between creatine kinase-isoenzyme MB (CK-MB) and c-troponin-T
      in patients with myocardial damage.

PMID- 8862475
TI  - Quantitation of urinary glycosaminoglycans with Alcian blue: evaluation of the
      interference by Tamm-Horsfall glycoprotein.

PMID- 8862476
TI  - Breakfasts high in protein, fat or carbohydrate: effect on within-day appetite
      and energy balance.
AB  - OBJECTIVE: To compare the effect of isoenergetically-dense, high-protein (HP),
      high-fat (HF) or high-carbohydrate (HC) breakfasts (at 08.30) on subjective
      hunger, fullness and appetite (measured hourly on a 100 mm visual analogue
      scale), macronutrient balance and ad libitum energy intake (EI), at a test meal
      (13.30) and throughout the rest of the day (until 23.00). DESIGN: Six men each
      spent 24 h in a whole-body indirect calorimeter on three separate occasions
      during which they received breakfasts designed to match 75% of BMR and that
      comprised, on average 3.1 MJ of protein (HP), carbohydrate (HC) or fat (HF),
      respectively, the remainder being split between the other two macronutrients.
      Every item of the ad libitum diet comprised 13% protein, 40% fat and 47%
      carbohydrate by energy, with an energy density of 550 kJ/100 g. RESULTS:
      Subjectively-rated pleasantness did not differ between the breakfasts, or any of
      the subsequent ad libitum meals. Subjective hunger was significantly greater
      during the hours between breakfast and lunch after the HF (26) treatment relative
      to the HP (18) or HC (18 mm) meals (P < 0.001), although the HP treatment
      suppressed hunger to a greater extent than the other two treatments over 24 h.
      However, mean ad libitum lunch intakes were similar at 5.38, 5.30 and 5.18 MJ
      (NS) on the HP, HC and HF treatments, respectively. After-lunch intakes were also
      very similar at 6.14, 6.18 and 5.83 MJ (NS). Mean 24-h energy expenditure
      amounted to 11.12, 11.14 and 10.93 MJ, respectively, producing energy balances of
      5.71, 5.83 and 5.04 MJ (NS), respectively. The HP, HF and HC breakfasts led to
      enhanced P, F and C oxidation, respectively (P < 0.003). CONCLUSIONS: Large HP,
      HC or HF breakfasts led to detectable changes in hunger that were not of
      sufficient magnitude to influence lunch-time intake 5 h later, or EI for the rest
      of the day. A single positive balance of each macronutrient can be buffered by
      oxidation and storage capacity, without leading to changes in meal-to-meal EI,
      when subjects feed ad libitum on unfamiliar diets of fixed composition.

PMID- 8862477
TI  - Effect of overfeeding macronutrients on day-to-day food intake in man.
AB  - OBJECTIVE: To test whether overfeeding isoenergetic doses protein, carbohydrate
      and fat would differentially influence appetite on the same day, and the
      subsequent day's food intake. DESIGN: Six men were each studied three times on a
      5-day protocol. On days 1 and 2 they were fed a medium fat (MF) maintenance diet
      (comprising 40:47:13% fat, CHO and protein by energy) calculated at 1.6 x RMR.
      Subjects entered the calorimeter at 08.00 on day 3 for 48 h. On day 3
      (manipulation day), they ate a MF diet at 1.5 x RMR with an additional 0.6 x RMR
      as protein (HP), carbohydrate (HC) or fat (HF). On days 4 and 5, (outcome days),
      subjects had ad libitum access to isoenergetically dense MF (40:47:13) foods
      (550kJ/100 g). Subjective hunger and satiety were tracked hourly during waking
      hours throughout days 1-5. RESULTS: Throughout day 3 subjects felt significantly
      more full and less hungry on the high protein diet relative to the other two
      diets (P = 0.002). Also by the end of day 3 each overfed nutrient led to a
      significant increase in its own balance of the other two diets (P < 0.01). These
      effects did not influence the subsequent day's energy intake. The alterations in
      nutrient balance by the end of day 3 were partially buffered by increases in the
      oxidative disposal of each overfed macronutrient throughout day 4 (which was
      proportionately greater for protein (P < 0.001) than carbohydrate (P = 0.07) or
      fat (P = 0.1)). CONCLUSIONS: HP diets were more satiating that isoenergetically
      dense HC or HF diets on the day they are eaten. The HC diet was transiently more
      satiating than the HF diet after each meal. This study supports previous work
      which suggests that relatively large changes in nutrient balance produced on one
      day appear to be poorly compensated by changes in energy intake on a subsequent
      day in men.

PMID- 8862478
TI  - Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.
AB  - OBJECTIVE: To study the association of serum calcium, magnesium, copper and zinc
      concentrations with cardiovascular mortality. DESIGN: A nested case-control study
      within a prospective population study. SUBJECTS AND METHODS: 230 men dying from
      cardiovascular diseases and 298 controls matched for age, place of residence,
      smoking and follow-up time. Mean follow-up time was 10 years. Serum calcium,
      magnesium, copper and zinc concentrations were determined from samples kept
      frozen at -20 degrees C. RESULTS: High serum copper and low serum zinc
      concentrations were significantly associated with an increased mortality from all
      cardiovascular diseases and from coronary heart disease in particular. The
      relative risk of coronary heart disease mortality between the highest and lowest
      tertiles of serum copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04),
      respectively. Adjustment for social class, serum cholesterol, body mass index,
      hypertension and known heart disease at baseline examination did not materially
      alter the results. No significant differences were observed in concentrations of
      serum calcium and magnesium between cases and controls. CONCLUSIONS: High serum
      copper and low serum zinc are associated with increased cardiovascular mortality
      whereas no association was found with serum calcium and magnesium and mortality
      risk.

PMID- 8862479
TI  - The importance of measured intake in assessing exposure of breast-fed infants to
      organochlorines.
AB  - OBJECTIVES: To estimate infants' intake of organochlorines (OCs) from their
      measured intake of breast milk; to compare these with the acceptable daily
      intakes (ADIs) set by the World Health Organization (WHO). DESIGN: Primiparous
      nursing mothers were recruited from either an industrial or rural area between
      January and November 1992. SETTING: Mothers volunteered in response to
      information displayed at their Infant Welfare Centre. All sampling was undertaken
      in the subject's home. SUBJECTS: The sole entry criterion was primiparity. Three
      breast milk samples were collected at one month intervals from each mother. OC
      levels were measured on a milk fat basis by gas chromatograph-mass spectrometer
      and individual milk intakes were used to determine the infant's daily OC intake.
      Of the 23 mothers who entered the study, 17 finished, resulting in 57 samples for
      intake determination. RESULTS: Some intakes of hexachlorobenzene (HCB),
      chlordane, dieldrin and heptachlor epoxide (HE) exceeded the ADI. High OC levels
      in breast milk did not necessarily result in a high intake for the infant.
      CONCLUSIONS: Assessment of the exposure of infants to OC contaminants in breast
      milk requires an accurate estimate of OC intake. Intakes estimated using inferred
      rather than measured values for milk fat and milk intake are not reliable
      indicators of actual intakes.

PMID- 8862480
TI  - Effect of 6 month supplementation with different combinations of an association
      of antioxidant nutrients on biochemical parameters and markers of the antioxidant
      defence system in the elderly. The Geriatrie/Min.Vit.Aox Network.
AB  - OBJECTIVES: To study the effect of supplementation with an association of small
      physiological amounts of antioxidant nutrients upon biochemical parameters and
      indicators of oxidative stress and antioxidant enzymes. DESIGN: The study
      included a double-blind placebo-controlled design. SETTING: Nursing homes in
      different areas in France. SUBJECTS: 575 elderly long term hospitalized subjects
      aged 65-103 years. INTERVENTION: Four groups were compared. They received daily:
      (V) vitamins (vitamin E, 15 mg and vitamin C, 120 mg) and beta-carotene, 6 mg;
      (T) trace elements (zinc, 20 mg, selenium, 100 micrograms); (VT) vitamins
      associated with trace elements; or (P) a placebo. Biological markers of vitamin
      and trace element status, and free radical parameters were measured initially and
      after 6 months of supplementation. RESULTS: An analysis of variance indicated a
      significant effect of vitamin supplementation on serum alpha-tocopherol, beta
      carotene and vitamin C, a significant effect of trace element supplementation on
      serum zinc and both a significant trace element and a vitamin-trace element
      interaction on serum selenium. We observed significant effects of both trace
      element and vitamin supplementation on GPx activity (P < 0.01), an effect of
      vitamin supplementation on SOD activity (P < 0.05). CONCLUSION: Our results
      indicate that short-term supplementation with moderate doses of antioxidant
      vitamins and trace elements in elderly subjects clearly improves both non
      enzymatic (alpha-tocopherol, beta-carotene, vitamin C) levels and enzymatic
      antioxidant (GPx and SOD) activity.

PMID- 8862481
TI  - The prevalence of anaemia and mineral supplement use in a Swedish middle-aged
      population. Results from the Malmo Diet and Cancer Study.
AB  - OBJECTIVE: To describe dietary habits and use of mineral supplements in relation
      to nutrient recommendations and anaemia. DESIGN: a population-based cohort study.
      SUBJECTS: 2665 men and 3878 women, born between 1926 and 1945, randomly invited
      and participating in the prospective 'Malmo Diet and Cancer study' during 1991
      1992. METHODS: The diet was assessed using a combined 7-day menu book for hot
      meals, beverages and supplements and a quantitative food frequency questionnaire
      for other foods. Anaemia was defined as haemoglobin < or = 131 g/l for men and <
      or = 115 g/l for women. RESULTS: Intake of mineral supplements were reported by
      19% of the men and 31% of the women. Less than 0.2% had intakes of iron and
      selenium above highest recommended Swedish long-term intakes. The percentage of
      women with intake below nutrient recommendations were: zinc and selenium (60%);
      magnesium (35%); calcium (21%) and iron (70%, premenopausal). The corresponding
      values for men were: zinc, selenium and magnesium (33-47%); calcium and iron
      (5%). The median contribution of calcium from supplements was less than 110 mg.
      Supplement users had higher intakes of fish, fruits, vegetables and tea and lower
      intakes of coffee and meat. The iron intake was correlated to haemoglobin levels,
      and iron supplementation constituted about 45% of the intake. Three per cent of
      premenopausal women had anaemia as did less than 2% of postmenopausal women.
      CONCLUSION: A substantial number had mineral intake below present recommendations
      despite supplement use. The nutrient content of some supplements could be
      improved, especially calcium. Iron supplementation among postmenopausal women and
      men are questionable.

PMID- 8862482
TI  - Vitamin A deficiency and protein-energy malnutrition in a sample of pre-school
      age children in the Kivu Province in Zaire.
AB  - OBJECTIVE: To assess pre-school age children's vitamin A status in a population
      where protein-energy malnutrition is endemic and serum retinol binding protein
      and transtyretin concentrations are low. DESIGN: A cross-sectional study.
      SETTING: Health district of Katana, South-Kivu, Zaire. SUBJECTS: 415 pre-school
      age children. METHODS: Three methods were used to assess vitamin A status:
      ophtalmological examination, retinol serum concentration and Relative Dose
      Response (RDR) test. RESULTS: The only ophthalmological signs of vitamin A
      deficiency appeared in two cases of night blindness, which represents a
      prevalence of 0.7%. Deficient serum retinol concentration (< 0.35 mumol/l) was
      found in 19.7% of the whole study population and in 10.4% of non-infected
      children in good nutritional status. RDR test carried out on a reduced sample of
      79 subjects was abnormal for 7.6% of the children but showed a low sensitivity
      when compared with serum retinol concentration. CONCLUSION: This survey suggests
      that in this population of the South-Kivu Province in Zaire, vitamin A deficiency
      co-exists with protein-energy malnutrition and is a public health problem even
      with non-malnourished and non-infected children.

PMID- 8862483
TI  - Height and weight reference charts for children aged 2-18 years from Verona,
      Italy.
AB  - OBJECTIVE: To compile curves for growth in weight and height for Italian children
      and adolescents. DESIGN: Cross-sectional. SETTING: All primary and secondary
      schools in the area of Verona, Italy, between October 1986 and January 1987.
      SUBJECTS: 20534 female and 20345 male children aged 2-18 years. METHODS: Weight
      and height were measured using Salus balances, and age in days was calculated
      between the date of measurement and that of birth: centiles of weight and height
      by age were calculated by the LMS method of Cole (1990). RESULTS: The height and
      weight curves were similar for both boys and girls to those obtained in
      Switzerland by Prader & Budliger (1977). However pre-pubertal Italian boys and
      girls are taller and heavier than the standards for France (Sempe & Pedron, 1953
      1970) or for the UK by Tanner & Whitehouse (1976).

PMID- 8862484
TI  - Acute PTH response to oral calcium load and seasonal variation of vitamin D
      status in healthy young adult subjects.
AB  - OBJECTIVE: The aim of the present study was to check the relationship between
      seasonal variations of vitamin D status and parathyroid function explored both in
      basal conditions and after oral calcium load. DESIGN: The calcium and parathyroid
      hormone response to the intake of calcium load was studied at two different
      seasons, before winter (November) and after winter (March-April), corresponding
      to different vitamin D status. SUBJECTS: Eighteen healthy young male adults (age:
      25 +/- 3 y) were studied. All were medical students who were selected as having
      no disorders known to affect calcium metabolism. INTERVENTION: At each period an
      oral calcium load (1 g of elemental calcium as calcium carbonate) was
      administered. Blood samples were collected before and 1 h, 2 h, 3 h and 4 h after
      the intake of calcium. Serum ionized calcium (Ca2+) and intact parathormone (PTH1
      84) were measured at each time point and 25-hydroxyvitamin D (25(OH)D) was
      measured before each calcium test. RESULTS: After winter, basal 25(OH)D
      concentrations were decreased (from 16.4 +/- 6.6 to 11.5 +/- 4.4 micrograms/l)
      and basal PTH concentrations were increased (from 24.1 +/- 6.5 to 31.7 +/- 9.1
      pg/ ml), and the difference between pre- and post-winter basal concentrations
      were statistically significant for both variables (P < 0.001). A statistically
      significant negative correlation between PTH and 25(OH)D was obtained both before
      (r = -0.63; P = 0.005) and after (r = -0.64; P = 0.004) winter. The maximum
      decrement in PTH (delta PTHmax) was not different before (13.92 +/- 4.58 pg/ml)
      and after (14.14 +/- 7.79 pg/ml) winter, but as a consequence of post-winter
      higher basal levels of PTH, at all time points after oral calcium load,
      concentrations of PTH after winter were significantly higher than before.
      CONCLUSIONS: The present results show that PTH concentrations are physiologically
      linked to 25(OH)D concentrations, and emphasize the need of taking into account
      the vitamin D status of each subject to predict the effect of an oral calcium
      load on absolute concentrations of PTH.

PMID- 8862485
TI  - Antioxidant vitamins in hospitalized elderly patients: analysed dietary intakes
      and biochemical status.
AB  - DESIGN: Descriptive study. SETTING: Geriatric department of the Grenoble
      University Hospital. SUBJECTS: 24 hospitalized elderly women: 13 long-stay
      patients and 11 in rehabilitation after femoral neck fracture. MAIN OUTCOME
      MEASURES: Retinol, carotene, tocopherol and vitamin C dietary intakes were
      evaluated by 5-day duplicate portion analysis. Circulating levels of retinol,
      beta-carotene, alpha-tocopherol and vitamin C were determined in parallel (HPLC).
      RESULTS: Mean intake of vitamin C (21 mg/d), and vitamin E (3.1 mg alpha
      tocopherol equivalents TE/d) were low compared to recommendations, in relation
      with poor energy intake (5.27 MJ/d) and nutrient densities. More than 85% of the
      patients exhibited vitamin C and vitamin E intakes below two-thirds the
      recommendations (60 mg/d and 10 mg TE/d, respectively) and 50% did not meet
      recommendations for vitamin A (800 micrograms retinol equivalents/d). With the
      exception of retinol, dietary vitamin intakes were positively correlated to
      corresponding blood concentrations. No values below cut-off levels were found
      concerning plasma retinol, plasma tocopherol or ratio of alpha-tocopherol to
      cholesterol. In contrast, 26% and 32% of the elderly patients had low circulating
      levels of beta-carotene and vitamin C, respectively. CONCLUSIONS: The present
      study highlights low antioxidant vitamin intakes, particularly concerning vitamin
      E and vitamin C, and an important proportion of low blood vitamin C and beta
      carotene concentrations in hospitalized elderly women. Further studies are needed
      to determine the actual requirements of hospitalized elderly patients and to
      evaluate the potential benefits of providing micronutrient-enriched foods to this
      population.

PMID- 8862486
TI  - Development of food frequency questionnaires in three population samples of
      African origin from Cameroon, Jamaica and Caribbean migrants to the UK.
AB  - OBJECTIVES: To develop the methods for assessment of food and nutrient intake
      using standardized food frequency questionnaires (FFQ) in three African origin
      populations from Cameroon, Jamaica and Caribbean migrants to the United Kingdom.
      DESIGN: Cross-sectional assessment of diet from a representative sample in each
      site, using either a 2-day food diary or a 24-h recall method to determine foods
      for inclusion on the food frequency questionnaire. SETTING: A rural and urban
      site in Cameroon, Evodoula and Cite Verte in Yaounde, respectively; a district in
      Kingston Jamaica; African-Caribbeans living in central Manchester, UK. SUBJECTS:
      Aged 25-79 years, 61 from the Cameroonian urban site, 62 from the village site;
      102 subjects from Jamaica (additional analysis on a subsample of 20): 29 subjects
      from Manchester, UK. MAIN OUTCOME MEASURES: Foods contributing to nutrients in
      each site to allow the development of a FFQ. RESULTS: A high response rate was
      obtained in each site. Comparison of macronutrient intakes between the sites
      showed that carbohydrate was the most important contributor to energy intake in
      Jamaica (55%) and the least in rural Cameroon. In rural Cameroon, fat (mainly
      palm oil) was the most important contributor to energy intake (44%). Manchester
      had the highest contribution of protein to energy (17%). Foods contributing to
      total energy, protein, fat and carbohydrate were determined. In rural Cameroon,
      the top 10 food items contributed 66% of the total energy intake compared to 37%
      for the top 10 foods in Manchester. Foods contributing to energy were similar in
      Jamaica and Manchester. Cassava contributed 44% of the carbohydrate intake in
      rural Cameroon and only 6% in urban Cameroon. One FFQ has been developed for use
      in both sites in Cameroon containing 76 food items. The FFQ for Jamaica contains
      69 foods and for Manchester 108 food items. CONCLUSION: Considerable variations
      exist within sites (Cameroon) and between sites in foods which are important
      contributors to nutrient intakes. With careful exploration of eating habits it
      has been possible to develop standardized, but locally appropriate FFQs for use
      in African populations in different countries.

PMID- 8862487
TI  - Validity of self-reported intakes of wine, beer and spirits in population
      studies.
AB  - OBJECTIVE: To compare data on intake of wine, beer and spirits from a frequency
      questionnaire with intake of each type of alcoholic beverage estimated from a
      dietary interview. DESIGN: Cross-sectional study. SETTING: The Danish MONICA
      study. SUBJECTS: A randomly selected sub-sample of 244 women and 249 men aged 35
      65 y. MAIN OUTCOME MEASURE: Differences in intake of beer, wine and spirits as
      reported by the frequency questionnaire and the diet history interview. RESULTS:
      There was an overall agreement between the two methods, with very little or no
      systematic variation for all three alcoholic beverages. CONCLUSION: Compared to a
      more time consuming and thorough dietary interview, the traditional frequency
      questionnaires seem to sufficiently capture intakes of different types of
      alcohol. Bias in alcohol reporting by the frequency questionnaire does not seem
      responsible for the recently found decreased mortality among subjects with a
      daily intake of wine, nor the increased mortality from spirits drinking.

PMID- 8862488
TI  - Adrenergic and serotoninergic receptors mediate the immunological activation of
      corticosterone secretion in male rats.
AB  - In order to elucidate the mechanism of action of immune agents on corticosterone
      secretion, the present study evaluated the possible involvement of some neuronal
      pathways (serotoninergic, noradrenergic/adrenergic) in the lipopolysaccharide
      (LPS)-induced corticosterone release in male rats. Serotoninergic antagonists,
      mianserin (5-HT2C receptor blocker) or pindolol (5HT1A receptor blocker) or
      noradrenergic/adrenergic antagonists, prazosin (alpha 1-adrenoceptor blocker) or
      propranolol (beta-adrenoceptor blocker), were intraperitoneally (i.p.) injected
      before (5 min) the administration of LPS. In each experiment a group of rats i.p.
      injected with vehicle served as controls. Animals were sacrificed by decapitation
      90 min after administration of LPS and trunk blood was collected for
      corticosterone radioimmunoassay. Results showed that pretreatment with mianserin,
      but not with pindolol, significantly reduced plasma corticosterone levels
      following administration of LPS (p < 0.05); prazosin attenuated the plasma
      corticosterone response to LPS (p < 0.05), while propranolol did not induce
      significant change. The present study indicated that serotoninergic and
      noradrenergic/adrenergic pathways are involved in the immunoneuroendocrine
      modulation of hypothalamus-pituitary-adrenal function in rats. In particular, it
      is probably mediated by the activation of 5-HT2C receptors and of alpha 1
      adrenoceptors, while type 1A serotonin receptors or beta-adrenoceptors do not
      seem to be involved in such a phenomenon.

PMID- 8862489
TI  - Changes in the erythrocyte antioxidant enzyme system during transdermal estradiol
      therapy for secondary amenorrhea.
AB  - Twenty-two hypothalamic amenorrheic patients, who were non-smokers and of normal
      weight, received replacement therapy for 1 month with transdermal patches
      containing 8 mg estradiol. No other drugs were prescribed or taken during the
      study. Before treatment (time 0) and 1 month after its start, blood samples were
      taken for assay of plasma estradiol levels, the erythrocyte antioxidant enzyme
      activities of superoxide dismutase, catalase, glutathione peroxidase (GSH-Px),
      and an age-dependent erythrocyte enzyme activity, pyruvate kinase. Plasma
      malondialdehyde levels, as an index of lipoperoxidation products, were also
      detected. The results showed no significant variations in superoxide dismutase,
      catalase, pyruvate kinase erythrocyte enzyme activities or plasma malondialdehyde
      levels. A significant increase in plasma estradiol levels (time 0, 17.33 +/- 4.12
      pg/ml; 1 month, 81.25 +/- 10.45 pg/ml; means +/- SD; p < 0.0001) and in GSH-Px
      erythrocyte activity (time 0, 11.97 +/- 2.31 IU/g hemoglobin; 1 month, 16.88 +/-
      4.38 IU/g hemoglobin; p < 0.004) was found. Plasma estradiol levels correlated
      significantly with GSH-Px erythrocyte activity 1 month after therapy was begun (r
      = 0.776, p < 0.003). We suggest that estrogens restored to physiological plasma
      levels, stimulate erythrocyte antioxidant GSH-Px activity, improving the
      antioxidant power of amenorrheic patients.

PMID- 8862490
TI  - The impact of GnRH agonist and menotropin therapy on lipoprotein metabolism.
AB  - Two groups of women, 48 undergoing controlled ovarian hyperstimulation for in
      vitro fertilization (IVF) treatment with a gonadotropin-releasing hormone (GnRH)
      analog and human menopausal gonadotropin daily and a group of 15 treated with a
      GnRH analog using the 'luteal phase protocol' before the hyperstimulation for
      IVF, took part in a prospective randomized study at the IVF Unit of the Beilinson
      Medical Center, Israel. The aim was to evaluate the changes in lipid metabolism
      occurring in the course of a standard controlled ovarian hyperstimulation
      protocol during IVF treatment cycles by measuring serum lipid levels before and
      after treatment. In the former group, in parallel with the 17 beta-estradiol
      increase, the cholesterol and low-density lipoprotein-cholesterol levels dropped
      and the high-density lipoprotein-cholesterol levels increased significantly. The
      resultant atherogenic index demonstrated a statistically significant decrease. In
      the latter group the mean lipoprotein levels were slightly different after
      treatment, but no statistically significant difference was observed. Our results
      indicate that the GnRH analog alone, administered for 10-12 days, does not induce
      any significant change in serum lipid levels. When using a combination of a GnRH
      analog and menotropins, the change of lipoprotein levels is favorable.

PMID- 8862491
TI  - Intranasal nafarelin versus buserelin (short protocol) for controlled ovarian
      hyperstimulation before in vitro fertilization: a prospective clinical trial.
AB  - The aim of this study was to compare the effect of nafarelin acetate with that of
      buserelin acetate nasal spray, when administered in a 'short' protocol, as an
      adjunct to human menopausal gonadotropin (hMG) for controlled ovarian
      hyperstimulation before in vitro fertilization (IVF). Twenty-two IVF subjects
      were randomly recruited. Each underwent two consecutive treatment cycles; one
      with buserelin (900 micrograms/day) and another with nafarelin (400
      micrograms/day). The treatment protocol included transnasal gonadotropin
      releasing hormone (GnRH) analog from the second cycle day and hMG from the fourth
      day of the cycle. The buserelin and nafarelin cycles did not differ significantly
      in the following parameters: baseline hormone profile, duration of GnRH analog
      treatment, mean hMG dose required, peak estradiol levels, number of preovulatory
      follicles, number of aspirated oocytes, fertilization rate and number of
      transferred or frozen embryos. No side-effects or cancellations of treatment were
      recorded. The average dose required was lower for nafarelin and, because this
      analog was given only twice a day, it was more convenient to administer. These
      findings suggest that nafarelin is as effective as buserelin (when administered
      in a "short' protocol) in achieving controlled ovarian hyperstimulation. It even
      offers advantages over buserelin with respect to the total dose required (which
      probably reflects its relatively high potency) and the subjects' compliance.

PMID- 8862492
TI  - The effects of 3-day clomiphene citrate treatment on endocrine and ovulatory
      responses.
AB  - A prospective cohort, paired clinical trial was carried out to test a shorter
      clomiphene citrate regimen of 3 days, measuring the endocrine outcomes and
      ovulatory responses. The trial took place at Gazi University Medical School
      Department of Obstetrics and Gynecology. The 28 infertile patients were newly
      accepted to the clinic with hypothalamopituitary disorder according to WHO
      classification Group II. They were treated with 50 mg/day clomiphene citrate (CC)
      for 3 days in 63 cycles. The control group of 28 paired patients were treated
      with 50 mg/day CC for 5 days in 40 cycles. The main outcome measures were: serum
      estradiol levels on day 11 (E-11), 14 (E-14) and postovulatory day 7 (E+ 7);
      serum progesterone levels on postovulatory day 7 (P+ 7); endometrial thickness on
      day 14 of the cycle; mean follicular phase length; and ovulation rates. The mean
      ages, gravidas, paritas, menstrual histories, E-11, P+ 7 levels, mean follicular
      phase length and luteal phase length were similar in both groups. E-14 (229.76 +/
      156.05 pg/ml vs. 338.25 +/- 350.60 pg/ml) and E+ 7 (217.30 +/- 114.95 pg/ml vs.
      310.6 +/- 11.05 pg/ml) were significantly lower, whereas mean endometrial
      thickness on day 14 (10.30 +/- 1.39 mm vs. 9.52 +/- 1.96 mm) were significantly
      higher in the study group compared to controls (p < 0.05). Ovulation occurred in
      82.53% of cycles in the study group and 95% in controls. In the study group,
      pregnancy was achieved in 17.3% of the ovulatory cycles; this rate was 10.5% in
      the control group. To decrease the peripheral antiestrogenic effects of CC, a
      regimen of 50 mg/day for 3 days may be used as a starting dose instead of the
      standard 5-day regimen.

PMID- 8862493
TI  - In situ hybridization study of messenger RNA for estrogen receptor and
      immunohistochemical detection of estrogen and progesterone receptors in the human
      ovary.
AB  - The expression of estrogen and progesterone receptors (ER and PR), as well as the
      presence of messenger RNA for estrogen receptor (ER-mRNA), were analyzed by
      immunohistochemistry and in situ hybridization, respectively, in the ovary of 25
      healthy eumenorrheic women. Ovarian biopsies were taken in different phases of
      the menstrual cycle during laparotomy or operative laparoscopy performed for
      extraovarian benign diseases. A total of 126 follicles (105 primordial, 13
      preantral and eight antral) and 50 corpora lutea (eight active and 42 atretic)
      was analyzed. Granulosa cells stained positively for ER, PR and ER-mRNA in 13.3,
      9.5 and 17.1% of primordial follicles, respectively. The proportions of preantral
      and antral follicles with ER-positive granulosa cells were 23.1 and 37.5%,
      respectively; these follicles were positive for PR in 23.1 and 37.5% of cases,
      and for ER-mRNA in 30.7 and 37.5% of cases, respectively. For thecal cells, 38.5%
      of preantral and 37.5% of antral follicles were PR-positive, but no more than 25%
      stained positive for ER and ER-mRNA. Active corpora lutea stained positive for
      ER, PR and ER-mRNA in 50, 62.5 and 50% of cases, respectively. Corpora albicantes
      always stained negative. In all subjects the stroma surrounding both follicles
      and corpora lutea contained several fibroblast-like cells which stained positive
      for ER, PR and ER-mRNA. Oocytes and blood vessels stained negative in all cases.
      This study supports the hypothesis that estrogens and progesterone play a role in
      the intraovarian regulation of follicle growth from the first steps of follicle
      development, and participate in the regulation of corpus luteum.

PMID- 8862494
TI  - Alteration of E-cadherin, alpha- and beta-catenin mRNA expression in human
      uterine endometrium during the menstrual cycle.
AB  - To study the biological functions of the adherens junction in uterine endometrium
      at the reproductive phase, we measured the levels of E-cadherin, alpha- and beta
      catenin mRNA in endometrium with or without an intramuscular injection of
      estradiol dipropionate in patients 5 days before hysterectomy. The levels of E
      cadherin, alpha- and beta-catenin mRNA in endometria of the proliferative phase
      were significantly less than those of the secretory phase. The treatment with
      estradiol dipropionate significantly reduced the levels of alpha- and beta
      catenin mRNA in endometria of the secretory phase, and tended to reduce that of E
      cadherin mRNA. In conclusion, the functions of the adherens junction, which
      regulates the adhesive capacity of endometrial epithelial cells, are considered
      to be activated after ovulation, and at least in part associated with nidation.

PMID- 8862495
TI  - Expression of basic fibroblast growth factor and its mRNA in uterine endometrium
      during the menstrual cycle.
AB  - To learn more about reproductive neovascularization after menstrual regression of
      the microvessels in uterine endometrium, the regulation of basic fibroblast
      growth factor (FGF) and its mRNA expression in the endometria of the menstrual
      cycle with or without treatment with estradiol dipropionate were determined by
      enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase
      chain reaction-Southern blot (RT-PCR-SB), respectively. The endometrial basic FGF
      level was increased in advance of proliferation, but decreased at the secretory
      phase. The expression of basic FGF mRNA in endometria during the proliferative
      phase did not alter, but it was decreased at the secretory phase. Estradiol
      dipropionate increased the expression of basic FGF and its mRNA in endometria of
      the secretory phase. Therefore, the constant high level of basic FGF mRNA might
      contribute to the synthesis and accumulation of basic FGF up to the late
      proliferative phase, and the accumulated basic FGF might be rapidly consumed in
      the secretory phase. Furthermore, basic FGF during the proliferative phase could
      plausibly contribute to capillary neovascularization, which could be regulated by
      sex steroids.

PMID- 8862496
TI  - Bone mineral density and hormone levels in menopausal Australian women.
AB  - To assess the relationships between bone mineral density (BMD) at the lumbar
      spine and femoral neck and menopausal status, age, physical variables, and
      lifestyle and gynecological factors. BMD and follicle-stimulating hormone (FSH),
      estradiol and inhibin levels were measured in 167 women born in Australia, aged
      46-57 years, who had no record of receiving hormone replacement therapy. Using
      the premenopausal group as a baseline, the FSH level was higher in peri- and
      postmenopausal subjects (p < 0.0005), and estradiol and inhibin levels in the
      postmenopausal women were lower (p < 0.0005). Mean (+/- SE) lumbar spine and
      femoral neck BMD were 15 +/- 3% and 10 +/- 3% lower, respectively, in
      postmenopausal than in premenopausal women. Lumbar spine BMD decreased with
      increasing age in perimenopausal women only (p < 0.005), and femoral neck BMD
      decreased with increasing age in the pre-, peri-(p < 0.05) and postmenopausal
      women. The difference between femoral neck BMD in the pre- and postmenopausal
      women was explained by the difference in age between these groups, whereas for
      lumbar spine BMD the menopausal status was an additional determining factor.
      There was a negative effect of smoking on femoral neck BMD (p < 0.05) in
      postmenopausal women. In the perimenopausal decade the femoral neck BMD is
      primarily dependent on age, whereas lumbar spine BMD is dependent on both age and
      menopausal status.

PMID- 8862497
TI  - The role of triphasic levonorgestrel in oral contraception: a review of metabolic
      and hemostatic effects.
AB  - Epidemiological studies suggesting a possible association between the use of
      combined oral contraceptives and an increased risk of cardiovascular disease have
      led to extensive investigations into the effect of oral contraceptives on lipid
      and carbohydrate metabolism, and on hemostasis. Since this association was
      originally suggested, the steroid dose in oral contraceptives has been
      significantly reduced and new progestogens have been developed. Also, triphasic
      formulations have been introduced which offer a well-balanced
      estrogen/progestogen ratio, allowing a further reduction in the progestogen dose
      per cycle, and thus helping to minimize unwanted metabolic and hemostatic
      effects. The metabolic interactions of triphasic levonorgestrel, the first
      triphasic formulation to be introduced, have received particular attention. Lipid
      metabolism appears to be largely unaffected by triphasic levonorgestrel, most
      studies reporting no significant change in high- (HDL-C) or low-density
      lipoprotein-cholesterol (LDL-C) levels. Several studies have reported a decrease
      in the lipoprotein subfraction HDL2-C levels, but in most cases measurements of
      the LDL-C/HDL-C and apolipoprotein A-1/B ratios reveal no clinically significant
      effects. Concerning lipids, most studies suggest that triphasic levonorgestrel
      has less metabolic impact than the monophasic formulation. In common with all
      currently available oral contraceptives, triphasic levonorgestrel appears to have
      some effect on carbohydrate metabolism. The study results vary, however; some
      investigators have found an impairment of glucose tolerance, whereas others have
      not detected any significant effect. Compared with lipid and carbohydrate
      metabolism, fewer studies have investigated the effect of triphasic
      levonorgestrel on hemostasis. In common with all estrogen-containing oral
      contraceptives, levonorgestrel appears to stimulate some procoagulant activity,
      elevating the levels of factors VII and X, and fibrinogen. However, the effect of
      triphasic levonorgestrel appears to be balanced, with most studies reporting a
      corresponding increase in anti-coagulant-fibrinolytic activity. Although most of
      the studies reviewed here reported some statistically significant metabolic
      interactions, many authors comment that the changes are probably not clinically
      relevant in terms of an altered risk of cardiovascular disease. The true risk of
      vascular disease associated with modern low-dose oral contraceptives remains to
      be confirmed when sufficient epidemiological data eventually become available.

PMID- 8862498
TI  - Value of buserelin testing in the evaluation of hirsute women.
AB  - It has been recently reported that many hirsute women are affected with
      functional ovarian hyperandrogenism (FOH)-a term that encompasses the
      heterogeneous polycystic ovary syndrome- and show an abnormal ovarian
      steroidogenic response to gonadotropin-releasing hormone (Gn-RH) agonists. The
      aims of the present study were to determine the prevalence of FOH by the
      assessment of 17-hydroxyprogesterone (17-OHP) response to the Gn-RH agonist
      buserelin, to correlate these abnormal responses to other parameters suggestive
      of PCOS, and to assess the possible adrenal origin of hyperandrogenism.
      Therefore, in 33 consecutive women with hirsutism serum LH, FSH, 17-OHP,
      dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), cortisol levels
      were evaluated in basal conditions and after the administration of buserelin (0.5
      mg sc) and ACTH (tetracosactide 0.25 mg iv). Two patients were affected with a
      non classic congenital adrenal hyperplasia (CAH)-21OH deficiency. In 5 other
      women ACTH test caused a rate increase 17-OHP (30-0)/30 min > 19 nmol/L/min (0.25
      +/- 0.03; mean +/- SE), suggesting the possible existence of heterozygote non
      classic CAH-21OH. One patient showed a DHEA-S response to ACTH (from 10.3 to 17.2
      mumol/L), which was compatible with late-onset 3 beta-Hydroxy-delta 5 steroid
      dehydrogenase deficiency. Out of the 25 patients with normal responsiveness to
      ACTH, 11 women (group A) showed higher 17-OHP and A levels, in comparison to
      normal women, both in basal conditions (17-OHP = 4.18 +/- 0.72 vs 1.74 +/- 0.34
      nmol/L, p < 0.005; A = 11.8 +/- 1.2 vs 6.0 +/- 0.7 nmol/L, p < 0.05) and after
      buserelin (17-OHP = 15.61 +/- 1.31 vs 6.96 +/- 0.9 nmol/L; A = 19.0 +/- 1.9 vs
      7.5 +/- 0.8 nmol/L; p < 0.001). In 6 of these 11 patients basal and buserelin
      stimulated LH levels were higher than in normals. The remaining 14 patients
      (group B) showed normal baseline and buserelin-stimulated 17-OHP and A
      concentrations. In this group only 2 patients had high basal and stimulated LH
      levels. An augmented LH/FSH ratio was present in 5 and 1 cases of groups A and B,
      and polycystic ovaries at ultrasonography were observed in 7 and 8 cases of
      groups A and B, respectively. It is to note that an abnormal 17-OHP response to
      buserelin was present also in 3 of the 5 patients with abnormal 17-OHP rise after
      ACTH test, suggesting an adrenal and ovarian cause of hyperandrogenism. In
      conclusion, an abnormal response to one or both stimulation test was present in
      57% of cases: an adrenal origin of hirsutism was detected in 15%, a combined
      adrenal and ovarian origin was found in 9% and an ovarian cause was present in
      33%. Buserelin testing is an useful means to reveal the presence of FOH.

PMID- 8862499
TI  - Current status of endemic goiter in Croatia: the results of a nationwide study
      (1995).
AB  - In the beginning of the nineties, 40 years after introduction of iodine
      prophylaxis in Croatia, on a basis of a frequent reports coming from general
      practitioners about the presence of a rather high prevalence of goiter among
      schoolchildren, a nationwide study was initiated with the aim to determine the
      real prevalence of goiter in the country. A total of 2856 schoolchildren of both
      sexes, aged 7-15 years, were included into the study. Investigations were
      designed in a way to cover most of geographical regions in Croatia and subjects
      were randomly selected. The prevalence of goiter in schoolchildren was assessed
      by palpation and in part by ultrasonography of the neck. At the same time urinary
      iodine excretion was measured and iodine content in salt samples was determined.
      The results have revealed the persistence of mild endemic goiter in inland parts
      of Croatia with the prevalence of 6-29% in the age group 7-11 years and those of
      10-43% among the age group 12-15 years. The overall goiter prevalence in
      schoolchildren in Croatia fluctuates from 8% to 35%. Such prevalence, most
      probably due to less than optimum iodine intake, is unlikely to change until
      iodine content of the salt is increased from its present level of 10 mg of Kl per
      kg of salt.

PMID- 8862500
TI  - Impairment of granulation tissue formation after menopause.
AB  - Formation of connective tissue is an essential step in the process of wound
      healing. After menopause an atrophy of connective tissues in skin, bone, and
      reproductive organs takes place. Using a dead-space wound healing model we
      measured collagen synthesis and deposition, and cell replication in the
      granulation tissue of 18 premenopausal and 23 peri- and postmenopausal women not
      receiving any hormonal therapy. In the postmenopausal group collagen synthesis
      and deposition and cell number in the granulation tissue were diminished. These
      results document the impairment of the granulation tissue formation after
      menopause.

PMID- 8862501
TI  - Effect of bromocriptine on insulin, growth hormone and prolactin responses to
      arginine in obesity.
AB  - Dopaminergic system seems to influence the regulation of insulin secretion,
      although in man conflicting data are reported. Furthermore, bromocriptine (BRC),
      a dopaminergic agonist, has been recently found to inhibit the seasonally
      occurring hyperinsulinemia and the increase in body weight in the hamster. On
      this basis, we investigated the effect of BRC on spontaneous and stimulated
      insulin secretion in human obesity. Six obese (BMI: 33.2 +/- 1.6 Kg/m2) underwent
      the administration of: 1) arginine (ARG, 0.5 g/Kg iv in 30 min), 2) BRC (2.5 mg
      po), 3) ARG+BRC. In each test plasma glucose and serum insulin, growth hormone
      (GH) and prolactin levels were determined. BRC did not significantly reduce
      spontaneous and ARG-induced insulin release. Baseline and stimulated glucose
      levels were also unchanged. BRC determined an increase in GH levels (3.7 +/- 1.3
      vs 0.5 +/- 0.3 microgram/l, p < 0.05), but failed to modify the somatotrope
      responsiveness to ARG. On the other hand, both spontaneous and stimulated PRL
      secretion were reduced by BRC (2.5 +/- 0.4 vs 6.7 +/- 1.1 micrograms/l, p < 0.05
      and 0.8 +/- 1.9 vs 11.0 +/- 2.1 micrograms/l, p < 0.05, respectively). Our
      results show that in obese patients the acute activation of dopaminergic
      receptors by bromocriptine fails to modify both basal and ARG-induced insulin
      release, while inhibits spontaneous and stimulated PRL secretion. Our data also
      show that the low GH response to arginine in obesity is not improved by the
      coadministration of bromocriptine, in agreement with the hypothesis that both
      substances act by the same mechanism, i.e. inhibition of endogenous somatostatin
      release.

PMID- 8862502
TI  - Congenital hypothyroidism: auxological retrospective study during the first six
      years of age.
AB  - We examined length, height and weight from birth to six years of age and head
      circumference during the first two years in 89 children with congenital
      hypothyroidism (CH). The patients were divided in two groups: children diagnosed
      by clinical criteria during the first year of life (group A) and children
      detected by neonatal screening (group B). Group A showed a complete catch up
      growth for height and weight 10 months after the beginning of the replacement
      therapy; to the contrary, group B did not show any difference for height and
      weight compared to normal standards. Head circumference, evaluated only in group
      B, was significantly higher in comparison with normal standards. When etiology of
      CH was taken into consideration, children with athyreosis showed a significantly
      lower length at birth and at three months of age and their growths curves
      normalized after institution of replacement therapy. In conclusion our data
      suggest a direct relationship between severity and duration of hormone deficiency
      and growth retardation and confirm that replacement therapy started within the
      first year of live in CH patients clinically diagnosed allows a catch up growth.

PMID- 8862503
TI  - Transfection with the cDNA of the human thyrotropin receptor of a poorly
      differentiated rat thyroid cell line (FRT).
AB  - A cell line derived from the Fisher rat thyroid (FRT), that does not have
      functional TSH receptor, was stably transfected with the cDNA of the human TSH
      receptor (h TSH-R). In wild FRT cells TSH (1-1000 mU/l) was unable to increase
      cAMP production, while 10-10000 nmol/l forskolin elicited a 10-30 fold cAMP
      stimulation. Two of the transfected clones were responsive to TSH in terms of
      cAMP production. In particular, the FRT-R3 transfected clone showed the highest
      sensitivity to the hormone with a 10 fold cAMP increase over the basal at 100
      mU/l TSH. The Northern blot analysis using a 2.4 kbp cDNA probe for the hTSH-R
      showed a band corresponding to the mRNA of TSH receptor in FRT-R3 cells, but not
      in wild FRT cells. In both cell types TSH was ineffective in stimulating growth
      assayed by 3H-thymidine incorporation into DNA. Hybridization with a probe for
      thyroperoxidase on polymerase chain reaction products after reverse transcription
      of mRNA showed that FRT-R3, as well as FRT cells, do not have a transcript for
      thyroperoxidase. In conclusion, the data reported in this paper show that the
      insertion of the hTSH-R cDNA in the genome of poorly differentiated rat thyroid
      cells results in the recovery of TSH-dependent adenylate cyclase, but not other
      differentiated thyroid cell functions.

PMID- 8862504
TI  - A 4-base pair deletion mutation of Gs alpha gene in a Japanese patient with
      pseudohypoparathyroidism.
AB  - Mutations in the guanine nucleotide binding protein alpha subunit (Gs alpha) have
      been found in patients with pseudohypoparathyroidism (PHP). We have screened the
      Gs alpha gene for mutations in a Japanese patient with this disorder and
      identified a novel 4-base pair deletion in exon 7 in codons 189-190. This
      deletion causes a frameshift and if synthesis of a truncated form of Gs alpha
      occurred, it would likely be biologically inactive. The patient was heterozygous
      for this deletion. The patient's mother and an unaffected brother were tested for
      the presence of this mutation. His mother had the same mutation, and although her
      serum calcium and parathyroid hormone levels were within the normal range, she
      had subcutaneous calcifications. Thus, this mutation appears to be necessary but
      not sufficient to cause the complete pseudohypoparathyroidism phenotype and thus,
      other unknown factors, either genetic or acquired, may be necessary for the full
      syndrome to occur.

PMID- 8862505
TI  - Cyproheptadine treatment in Cushing's disease.
AB  - Cyproheptadine, a nonselective 5-hydroxytryptamine receptor blocking agent,
      reduces ACTH and beta-endorphin secretion from the ACTH-producing tumors. A 35
      year-old female suffering from Cushing's disease due to microadenoma of the
      pituitary gland has been followed since the age of 15. Subtotal adrenalectomy
      followed by total adrenalectomy, pituitary irradiation, and transsphenoidal
      hypophysectomy, combined with second radiotherapy of the pituitary, were
      unsuccessful in achieving remission of the disease. Remission was achieved with
      cyproheptadine up to a dosage of 24 mg/day. Every attempt to discontinue
      cyproheptadine treatment was accompanied by recurrence of the disease. This is
      the first case of Cushing's disease in which cyproheptadine treatment has been
      the only efficacious therapy for a period of 11 yr. Cyproheptadine may be an
      alternative long-term therapy for Cushing's disease when other methods of
      treatment fail.

PMID- 8862506
TI  - A prolactin-secreting tumor in a patient with Klinefelter's syndrome: a case
      report.
AB  - We report the case of a patient with Klinefelter's syndrome who developed a
      prolactin (PRL)-secreting tumor. The patient developed headaches, visual
      alterations and also symptoms of hypogonadism despite appropriate testosterone
      (T) replacement therapy. The diagnosis of hyperprolactinemia was then suspected.
      The laboratory findings confirmed the hypothesis, showing high levels of serum
      PRL. The patient was initially treated with oral bromocriptine, and afterwards
      with the injectable form. There was a marked decrease in PRL levels and in tumor
      size. Although some neoplasms, like breast carcinoma and germ cell tumors, are
      known to occur more frequently in patients with Klinefelter's syndrome, an
      association with PRL-secreting tumor has not been reported yet. In conclusion,
      symptoms of hypogonadism in patients with Klinefelter's syndrome receiving
      appropriate T replacement therapy can suggest the presence of hyperprolactinemia.

PMID- 8862507
TI  - Oral glucose tolerance test: an inhibitory or a stimulatory input to growth
      hormone secretion?

PMID- 8862508
TI  - Molar pregnancies associated with clomiphene citrate.

PMID- 8862509
TI  - Science and clinical medicine: a marriage made in heaven?

PMID- 8862510
TI  - Multiple sclerosis: an altered immune response or an altered stress response?
AB  - The pathogenesis of multiple sclerosis (MS), the major neurological disease of
      young adults in the Western world, is still poorly understood, and no effective
      therapy to block MS is available as yet. The clinical symptoms of MS result from
      inflammatory damage to the insulating myelin sheath of axons in the CNS and-at
      later stages-to axons themselves. A local autoimmune process involving activation
      of helper T cells against CNS protein components is likely to be crucial in this
      development. Especially at the first stages of MS, therapies aimed at the
      selective downregulation of MS-specific autoimmune responses may contribute to
      controlling the disease. Key to the success of such approaches is the
      identification of CNS proteins that are the target of local T cell responses. We
      recently identified the small heat-shock protein alpha B-crystallin as the single
      immunodominant myelin antigen in MS-affected myelin. This review discusses the
      functional and therapeutic implications of this finding along with other data on
      MS, and hypothesizes that an inappropriate stress response within the CNS itself
      is crucial as an initiating event in disease development.

PMID- 8862512
TI  - Molecular oncology in pancreatic cancer.
AB  - Cancer of the pancreas still has a very poor prognosis despite improved
      diagnostic methods and therapeutic regimens. The reasons for the aggressiveness
      of this cancer are not known, and the molecular mechanisms that govern the growth
      of pancreatic cancer cells are still not clearly defined. During the past two
      decades the development of new molecular biological techniques has offered new
      perspectives for a better understanding of pancreatic cancer. Tumor markers such
      as CA19-9 and CEA are used for diagnosis and for following the postoperative
      course of cancer patients. Characterization of pancreatic cancer cells using
      several molecular biological techniques has revealed overexpression or altered
      expression of growth factors and adhesion molecules, implying altered cell-cell
      and growth-regulatory interactions. In pancreatic cancer mutations in oncogenes
      and tumor suppressor genes are frequently detected in p53 and K-ras. This article
      reviews the possible molecular approaches for diagnosis, prognosis, or even
      therapy of pancreatic cancer.

PMID- 8862511
TI  - Cancer risk and oxidative DNA damage in man.
AB  - In living cells reactive oxygen species (ROS) are formed continuously as a
      consequence of metabolic and other biochemical reactions as well as external
      factors. Some ROS have important physiological functions. Thus, antioxidant
      defense systems cannot provide complete protection from noxious effects of ROS.
      These include oxidative damage to DNA, which experimental studies in animals and
      in vitro have suggested are an important factor in carcinogenesis. Despite
      extensive repair oxidatively modified DNA is abundant in human tissues, in
      particular in tumors, i.e., in terms of 1-200 modified nucleosides per 10(5)
      intact nucleosides. The damaged nucleosides accumulate with age in both nuclear
      and mitochondrial DNA. The products of repair of these lesions are excreted into
      the urine in amounts corresponding to a damage rate of up to 10(4) modifications
      in each cell every day. The most abundant of these lesions, 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG), is also the most mutagenic, resulting in GT
      transversions which are frequently found in tumor relevant genes. A series of
      other oxidative modifications of base and sugar residues occur frequently in DNA,
      but they are less well studied and their biological significance less apparent.
      The biomarkers for study of oxidative DNA damage in humans include urinary
      excretion of oxidized nucleosides and bases as repair products and modifications
      in DNA isolated from target tissue or surrogate cells, such as lymphocytes. These
      biomarkers reflect the rate of damage and the balance between the damage and
      repair rate, respectively. By means of biomarkers a number of important factors
      have been studied in humans. Ionizing radiation, a carcinogenic and pure source
      of ROS, induced both urinary and leukocyte biomarkers of oxidative DNA damage.
      Tobacco smoking, another carcinogenic source of ROS, increased the oxidative DNA
      damage rate by 35-50% estimated from the urinary excretion of 8-oxodG, and the
      level of 8-oxodG in leukocytes by 20-50%. The main endogenous source of ROS, the
      oxygen consumption, showed a close correlation with the 8-oxodG excretion rate
      although moderate exercise appeared to have no immediate effect. So far, cross
      sectional study of diet composition and intervention studies, including energy
      restriction and antioxidant supplements, have generally failed to show an
      influence on the oxidative DNA modification. However, a diet rich of Brussels
      sprouts reduced the oxidative DNA damage rate, estimated by the urinary excretion
      of 8-oxodG, and the intake of vitamin C was a determinant for the level of 8
      oxodG in sperm DNA. A low-fat diet reduced another marker of oxidative DNA damage
      in leukocytes. In patients with diseases associated with a mechanistically based
      increased risk of cancer, including Fanconi anemia, chronic hepatitis, cystic
      fibrosis, and various autoimmune diseases, the biomarker studies indicate an
      increased rate of oxidative DNA damage or in some instances deficient repair.
      Human studies support the experimentally based notion of oxidative DNA damage as
      an important mutagenic and apparently carcinogenic factor. However, the proof of
      a causal relationship in humans is still lacking. This could possibly be
      supported by demonstration of the rate of oxidative DNA damage as an independent
      risk factor for cancer in a prospective study of biobank material using a nested
      case control design. In addition, oxidative damage may be important for the aging
      process, particularly with respect to mitochondrial DNA and the pathogenesis of
      inflammatory diseases.

PMID- 8862514
TI  - Gene expression of the human prostaglandin E receptor EP4 subtype: differential
      regulation in monocytoid and lymphoid lineage cells by phorbol ester.
AB  - We isolated a cDNA clone encoding the human prostaglandin (PG) E receptor EP4
      subtype and examined the gene expression in human blood cells. Northern blot
      analysis revealed that the EP4 gene is expressed at a high level in peripheral
      blood mononuclear cells, and at lower levels in cultured human blood cell lines,
      THP-1 and U937 (monocytoid cell lines), MOLT-4 and Jurkat (T-cell lines), and
      Raji (B-cell line). To examine regulation of the EP4 gene expression in the
      immune system, we studied the effects of phorbol 12-myristate 13-acetate (PMA) on
      these cell lines. Gene expression was upregulated in THP-1, U937, and Raji cells
      by PMA, and was downregulated in MOLT-4 and Jurkat cells. In THP-1 cells the
      effects of PMA were further analyzed, and the upregulation of the EP4 gene was
      shown to be followed by an increase in PGE2 binding sites and in PGE2-induced
      cAMP accumulation. In the striking contrast, other PGE receptor subtypes (EP1,
      EP2 and EP3) and other prostanoid receptors (IP and DP) were shown not to be
      upregulated by PMA. Therefore, this is the first demonstration of a highly
      specific upregulation of the EP4 subtype in THP-1 cells treated with PMA,
      suggesting the importance of the EP4 subtype in the immune system. In the present
      study we also clarified that EP4 gene expression is regulated differently among
      human monocytoid and lymphoid lineage cells, thus leading to the better
      understanding of the regulatory mechanisms for the human EP4 gene expression in
      the immune system.

PMID- 8862513
TI  - Sarcoplasmic reticulum Ca2+ATPase and phospholamban mRNA and protein levels in
      end-stage heart failure due to ischemic or dilated cardiomyopathy.
AB  - Abnormalities in intracellular Ca2+ handling play a crucial role in the
      pathogenesis of heart failure. The reduced capacity of failing human myocardium
      to restore low resting Ca2+ levels during diastole has been explained by the
      impairment of Ca2+ uptake into the sarcoplasmic reticulum (SR) via the SR
      Ca2+ATPase. It is unclear whether Ca2+ATPase function, protein levels, and mRNA
      steady-state levels correspond to one other, and whether the cause of heart
      failure, namely idiopathic dilated or ischemic cardiomyopathy, produces different
      changes. The present study examined SR Ca2+ATPase activity and both mRNA and
      protein levels of SR Ca2+ATPase, phospholamban, and Gi alpha 2 in left
      ventricular myocardium from eight nonfailing hearts, from eight hearts of
      patients with idiopathic dilated cardiomyopathy (DCM), and from six hearts from
      patients with ischemic cardiomyopathy (ICM). Compared to nonfailing myocardium,
      the activity of the SR Ca2+ATPase was significantly reduced in failing myocardium
      from patients with DCM (36%, P < 0.01) and from patients with ICM (37%, P <
      0.001). Significantly lower levels of SR Ca2+ATPase mRNA levels (55% and -56%, P
      < 0.001 for DCM and ICM, respectively) and phospholamban mRNA (45%, P < 0.001 for
      DCM; 31%, P < 0.05 for ICM) were observed in failing than in nonfailing
      myocardium. In contrast, no significant changes were observed at the level of
      proteins, Gi alpha 2 mRNA and protein levels were both significantly increased in
      failing myocardium. There were no differences between idiopathic dilated and
      ischemic cardiomyopathy concerning the examined parameter. It is concluded that
      reduced SR Ca2+ATPase activity contributes to an altered intracellular Ca2+
      handling by the SR in both dilated and ischemic cardiomyopathic hearts. However,
      changes in SR Ca2+ATPase and phospholamban steady-state protein levels do not
      contribute to these alterations. The dissociation between protein and mRNA levels
      provides evidence for a posttranscriptional or post-translational regulation of
      these proteins. The observed alterations are not dependent on the underlying
      cause of end-stage heart failure.

PMID- 8862515
TI  - Elevated venous glutamate levels in (pre)catabolic conditions result at least
      partly from a decreased glutamate transport activity.
AB  - Abnormally high postabsorptive venous plasma glutamate levels have been reported
      for several diseases that are associated with a loss of body cell mass including
      cancer, human/simian immunodeficiency virus infection, and amyotrophic lateral
      sclerosis. Studies on exchange rates in well-nourished cancer patients now show
      that high venous plasma glutamate levels may serve as a bona fide indicator for a
      decreased uptake of glutamate by the peripheral muscle tissue in the
      postabsorptive period and may be indicative for a precachectic state. High
      glutamate levels are also moderately correlated with a decreased uptake of
      glucose and ketone bodies. Relatively high venous glutamate levels have also been
      found in non-insulin-dependent diabetes mellitus and to some extent also in the
      cubital vein of normal elderly subjects, i.e., in conditions commonly associated
      with a decreased glucose tolerance and progressive loss of body cell mass.

PMID- 8862517
TI  - cDNA cloning and characterization of a novel nucleolar protein.
AB  - In an initial study of anti-nuclear antibodies in the chronic inflammatory
      bladder disease interstitial cystitis, we reported that 7% of interstitial
      cystitis patients studied had autoantibodies to the nucleolus. We now report
      that, using an autoimmune serum from a patient with interstitial cystitis, we
      have identified and partially characterized a novel protein with an M(r) of
      approximately 55 kDa (hereafter referred to as No55) localized to the granular
      component of the nucleolus. No55 was initially characterized by diffuse nucleolar
      immunofluorescence staining in interphase cells and by Western blotting as a 55
      kDa doublet on whole-cell extracts. During mitosis, No55 was associated with
      chromosomes and appeared in prenucleolar bodies during telophase, but it did not
      colocalize with p80-coilin in coiled bodies. Immunoelectron microscopy revealed
      that No55 was localized uniformly throughout the granular component of the
      nucleolus compared with a more peripheral localization of nucleolar granular
      component protein B23. On segregation of the nucleolus with actinomycin D, No55
      remained with the granular component of the segregated nucleolus, whereas protein
      B23 was found predominantly in the nucleoplasm. Finally, a cDNA expression
      library was screened with the human autoantibody against No55, and a 2.4-kb
      insert was isolated, subcloned to homogeneity, and then sequenced. Analysis of
      this sequence showed an open reading frame of approximately 1.3 kb coding for 437
      amino acids with a predicted molecular weight of 50 kDa. A search of the gene
      sequence database indicated homology with SC65, a rat synaptonemal complex
      protein. Therefore, on the basis of molecular weight, nucleolar sublocalization,
      response to actinomycin D, and cDNA sequence determination, No55 is a novel
      protein of the interphase nucleolus.

PMID- 8862516
TI  - Proteins in unexpected locations.
AB  - Members of all classes of proteins--cytoskeletal components, secreted growth
      factors, glycolytic enzymes, kinases, transcription factors, chaperones,
      transmembrane proteins, and extracellular matrix proteins--have been identified
      in cellular compartments other than their conventional sites of action. Some of
      these proteins are expressed as distinct compartment-specific isoforms, have
      novel mechanisms for intercompartmental translocation, have distinct endogenous
      biological actions within each compartment, and are regulated in a compartment
      specific manner as a function of physiologic state. The possibility that many, if
      not most, proteins have distinct roles in more than one cellular compartment has
      implications for the evolution of cell organization and may be important for
      understanding pathological conditions such as Alzheimer's disease and cancer.

PMID- 8862518
TI  - Mechanisms of integrin-mediated calcium signaling in MDCK cells: regulation of
      adhesion by IP3- and store-independent calcium influx.
AB  - Peptides containing Arg-Gly-Asp (RGD) immobilized on beads bind to integrins and
      trigger biphasic, transient increases in intracellular free Ca2+ ([Ca2+]i) in
      Madin-Darby canine kidney epithelial cells. The [Ca2+]i increase participates in
      feedback regulation of integrin-mediated adhesion in these cells. We examined
      influx pathways and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ store
      release as possible sources of the [Ca2+]i rise. The RGD-induced [Ca2+]i response
      requires external Ca2+ (threshold approximately 150 microM), and its magnitude is
      proportional to extracellular calcium. RGD-induced transients were attenuated by
      Ca2+ channel inhibitors (Ni2+ and carboxy-amidotriazole) or by plasma membrane
      depolarization, indicating that Ca2+ influx contributes to the response. Loading
      cells with heparin reduced the size of RGD-induced [Ca2+]i transients, indicating
      that IP3-mediated release of Ca2+ from stores may also contribute to the RGD
      response. Depletion of Ca2+ stores with thapsigargin activated Ni(2+)-sensitive
      Ca2+ influx that might also be expected to occur after IP3-mediated depletion of
      stored Ca2-. However, RGD elicited a Ni(2+)-sensitive Ca2+ influx even after
      pretreatment with thapsigargin, indicating that Ca2+ influx is controlled by a
      mechanism independent of IP3-mediated store depletion. We conclude that RGD
      induced [Ca2+]i transients in Madin-Darby canine kidney cells result primarily
      from the combination of two distinct mechanisms: 1) IP3-mediated release of
      intracellular stores, and 2) activation of a Ca2+ influx pathway regulated
      independently of IP3 and Ca2+ store release. Because Ni2+ and carboxy
      amidotriazole inhibited adhesion, whereas store depletion with thapsigargin had
      little effect, we suggest that the Ca2+ influx mechanism is most important for
      feedback regulation of integrin-mediated adhesion by increased [Ca2+]i.

PMID- 8862519
TI  - Genes that control the fidelity of endoplasmic reticulum to Golgi transport
      identified as suppressors of vesicle budding mutations.
AB  - Although convergent evidence suggests that proteins destined for export from the
      endoplasmic reticulum (ER) are separated from resident ER proteins and are
      concentrated into transport vesicles, the proteins that regulate this process
      have remained largely unknown. In a screen for suppressors of mutations in the
      essential COPII gene SEC13, we identified three genes (BST1, BST2/EMP24, and
      BST3) that negatively regulate COPII vesicle formation, preventing the production
      of vesicles with defective or missing subunits. Mutations in these genes slow the
      secretion of some secretory proteins and cause the resident ER proteins Kar2p and
      Pdi1p to leak more rapidly from the ER, indicating that these genes are also
      required for proper discrimination between resident ER proteins and Golgi-bound
      cargo molecules. The BST1 and BST2/EMP24 genes code for integral membrane
      proteins that reside predominantly in the ER. Our data suggest that the BST gene
      products represent a novel class of ER proteins that link the regulation of
      vesicle coat assembly to cargo sorting.

PMID- 8862520
TI  - Altered levels of the Drosophila HRB87F/hrp36 hnRNP protein have limited effects
      on alternative splicing in vivo.
AB  - The Drosophila melanogaster genes Hrb87F and Hrb98DE encode the fly proteins
      HRB87F and HRB98DE (also known as hrp36 and hrp38, respectively) that are most
      similar in sequence and function to mammalian A/B-type hnRNP proteins. Using
      overexpression and deletion mutants of Hrb87F, we have tested the hypothesis that
      the ratio of A/B hnRNP proteins to SR family proteins modulates certain types of
      alternative splice-site selection. In flies in which HRB87F/hrp36 had been
      overexpressed 10- to 15-fold above normal levels, aberrant internal exon skipping
      was induced in at least one endogenous transcript, the dopa decarboxylase (Ddc)
      pre-mRNA, which previously had been shown to be similarly affected by excess
      HRB98DE/hrp38. In a second endogenous pre-mRNA, excess HRB87F/hrp36 had no effect
      on alternative 3' splice-site selection, as expected from mammalian hnRNP
      studies. Immunolocalization of the excess hnRNP protein showed that it localized
      correctly to the nucleus, specifically to sites on or near chromosomes, and that
      the peak of exon-skipping activity in Ddc RNA correlated with the peak of
      chromosomally associated hnRNP protein. The chromosomal association and level of
      the SR family of proteins were not significantly affected by the large increase
      in hnRNP proteins during this time period. Although these results are consistent
      with a possible role for hnRNP proteins in alternative splicing, the more
      interesting finding was the failure to detect significant adverse effects on
      flies with a greatly distorted ratio of hnRNPs to SR proteins. Electron
      microscopic visualization of the general population of active genes in flies
      overexpressing hnRNP proteins also indicated that the great majority of genes
      seemed normal in terms of cotranscriptional RNA processing events, although there
      were a few abnormalities consistent with rare exon-skipping events. Furthermore,
      in a Hrb87F null mutant, which is viable, the normal pattern of Ddc alternative
      splicing was observed, indicating that HRB87F/hrp36 is not required for Ddc
      splicing regulation. Thus, although splice-site selection can be affected in at
      least a few genes by gross overexpression of this hnRNP protein, the combined
      evidence suggests that if it plays a general role in alternative splicing in
      vivo, the role can be provided by other proteins with redundant functions, and
      the role is independent of its concentration relative to SR proteins.

PMID- 8862521
TI  - Syntaxin 4 in 3T3-L1 adipocytes: regulation by insulin and participation in
      insulin-dependent glucose transport.
AB  - Syntaxins are thought to be membrane receptors that bind proteins of the
      synaptobrevin/vesicle-associated membrane protein (VAMP) family found on
      transport vesicles. Recently, we detected synaptobrevin II and cellubrevin on
      immunopurified vesicles containing the glucose transporter 4 (GLUT4) in insulin
      responsive cells. In an effort to identify the plasma membrane receptors for
      these vesicles, we now examine the expression of syntaxins in the 3T3-L1
      adipocyte cell line. Neither syntaxin 1A nor 1B was found, in keeping with the
      neuronal restriction of these isoforms. In contrast, syntaxins 2 and 4 were
      readily detectable. By subcellular fractionation and estimation of protein
      yields, 67% of syntaxin 4 was localized to the plasma membrane, 24% to the low
      density microsomes, and 9% to the high-density microsomes. Interestingly, acute
      insulin treatment decreased the content of syntaxin 4 in low-density microsomes
      and caused a corresponding gain in the plasma membrane fraction, reminiscent of
      the recruitment of GLUT4 glucose transporters. In contrast, there was no change
      in the distribution of syntaxin 2, which was mostly associated in the plasma
      membrane. A fraction of the intracellular syntaxin 4 was recovered with
      immunopurified GLUT4-containing vesicles. Moreover, anti-syntaxin 4 antibodies
      introduced in permeabilized 3T3-L1 adipocytes significantly reduced the insulin
      dependent stimulation of glucose transport, in contrast to the introduction of
      irrelevant immunoglobulin G, which was without consequence. We propose that
      either the plasma membrane and/or the vesicular syntaxin 4 are involved in
      docking and/or fusion of GLUT4 vesicles at the cell surface of 3T3-L1 adipocytes.

PMID- 8862522
TI  - A connection between pre-mRNA splicing and the cell cycle in fission yeast:
      cdc28+ is allelic with prp8+ and encodes an RNA-dependent ATPase/helicase.
AB  - The fission-yeast gene cdc28+ was originally identified in a screen for
      temperature-sensitive mutants that exhibit a cell-division cycle arrest and was
      found to be required for mitosis. We undertook a study of this gene to understand
      more fully the general requirements for entry into mitosis. Cells carrying the
      conditional lethal cdc28-P8 mutation divide once and arrest in G2 after being
      shifted to the restrictive temperature. We cloned the cdc28+ gene by
      complementation of the temperature-sensitive growth arrest in cdc28-P8. DNA
      sequence analysis indicated that cdc28+ encodes a member of the DEAH-box family
      of putative RNA-dependent ATPases or helicases. The Cdc28 protein is most similar
      to the Prp2, Prp16, and Prp22 proteins from budding yeast, which are required for
      the splicing of mRNA precursors. Consistent with this similarity, the cdc28-P8
      mutant accumulates unspliced precursors at the restrictive temperature.
      Independently, we isolated a temperature-sensitive pre-mRNA splicing mutant prp8
      1 that exhibits a cell-cycle phenotype identical to that of cdc28-P8. We have
      shown that cdc28 and prp8 are allelic. These results suggest a connection between
      pre-mRNA splicing and progression through the cell cycle.

PMID- 8862523
TI  - Abrogation of the Fc gamma receptor IIA-mediated phagocytic signal by stem-loop
      Syk antisense oligonucleotides.
AB  - The role of Syk kinase in Fc gamma receptor (Fc gamma R) IIA-mediated
      phagocytosis was examined with two forms of antisense oligodeoxynucleotides
      (ODNs) designed to hybridize to human Syk mRNA. Monocytes were incubated with
      linear and stem-loop antisense ODNs targeted to Syk mRNA. When complexed with
      cationic liposomes, stem-loop Syk antisense ODN with phosphorothioate
      modification exhibited stability in fetal bovine and human serum. The stem-loop
      Syk antisense ODN at a concentration of 0.2 microM inhibited Fc gamma RIIA
      mediated phagocytosis by 90% and completely eliminated Syk mRNA and protein in
      monocytes, whereas scrambled-control ODNs had no effect. The Syk antisense ODNs
      did not change beta-actin mRNA levels and Fc gamma RII cell-surface expression.
      In addition, stem-loop Syk antisense ODN inhibited Fc gamma RI and Fc gamma RIIIA
      mediated phagocytosis. These data indicate the efficacy of stem-loop Syk
      antisense ODN for targeting and degrading Syk mRNA and protein and the importance
      of Syk kinase in Fc gamma receptor-mediated phagocytosis. Immunoblotting assay
      demonstrated that Fc gamma RII tyrosine phosphorylation after Fc gamma RII cross
      linking did not change in the absence of Syk protein. These results indicate that
      Syk kinase is required for Fc gamma RIIA-mediated phagocytic signaling and that
      Fc gamma RII cross-linking leads to tyrosine phosphorylation of Fc gamma RII
      independent of Syk kinase.

PMID- 8862525
TI  - Structure-function studies of the myosin motor domain: importance of the 50-kDa
      cleft.
AB  - We used random mutagenesis to create 21 point mutations in a highly conserved
      region of the motor domain of Dictyostelium myosin and classified them into three
      distinct groups based on the ability to complement myosin null cell phenotypes:
      wild type, intermediate, and null. Biochemical analysis of the mutated myosins
      also revealed three classes of mutants that correlated well with the phenotypic
      classification. The mutated myosins that were not fully functional showed defects
      ranging from ATP nonhydrolyzers to myosins whose enzymatic and mechanical
      properties are uncoupled. Placement of the mutations onto the three-dimensional
      structure of myosin showed that the mutated region lay along the cleft that
      separates the active site from the actin-binding domain and that has been shown
      to move in response to changes at the active site. These results demonstrate that
      this region of myosin plays a key role in transduction of chemical energy to
      mechanical displacement.

PMID- 8862524
TI  - Post-transcriptional regulation of sex determination in Caenorhabditis elegans:
      widespread expression of the sex-determining gene fem-1 in both sexes.
AB  - The fem-1 gene of C. elegans is one of three genes required for all aspects of
      male development in the nematode. Current models of sex determination propose
      that the products of the fem genes act in a novel signal-transduction pathway and
      that their activity is regulated primarily at the post-translational level in
      somatic tissues. We analyzed the expression of fem-1 to determine whether it
      revealed any additional levels of regulation. Both XX hermaphrodites and XO males
      express fem-1 at approximately constant levels throughout development. Somatic
      tissues in hermaphrodites adopt female fates, but they nonetheless express fem-1
      mRNA and FEM-1 protein, suggesting that the regulation of fem-1 activity is post
      transcriptional and probably post-translational. A compact promoter directs
      functional expression of fem-1 transgenes, as assayed by their masculinizing
      activity in fem-1 mutants. Activity also requires any two or more introns,
      suggesting that splicing may enhance fem-1 expression. The minimal noncoding
      sequences required for activity of fem-1 transgenes suffice to direct expression
      of a fem-1::lacZ reporter gene in all somatic tissues in both sexes. Many fem-1
      transgenes, including those that rescue male somatic development in fem-1
      mutants, paradoxically feminize the germline. We suggest that they do so by
      interfering with the germline expression of the endogenous fem-1 gene.

PMID- 8862527
TI  - Parenteral use of medium-chain triglycerides: a reappraisal.
AB  - Over the last two decades, the clinical use of intravenous fat emulsions for the
      nutritional support of hospitalized patients has become routine. During this time
      long-chain triglycerides (LCT) derived from soybean and/or safflower oils were
      the exclusive lipid source for these emulsions, providing both a safe calorically
      dense alternative to dextrose and essential fatty acids needed for biologic
      membranes and the maintenance of immune function. During the past decade, the
      availability of novel experimental triglycerides for parenteral use has generated
      interest in the use of these substrates for nutritional and metabolic support.
      Medium-chain triglycerides (MCT), long advocated as a superior substrate for
      parenteral use, possess many unique physiochemical and metabolic properties that
      make them theoretically advantageous over their LCT counterparts. Although not
      yet approved in the United States, preparations containing MCT have been widely
      available in Europe. Intravenous MCT preparations, either as physical mixtures or
      structured lipids, have been used clinically in patients with immunosuppresion,
      critical illness, liver and pulmonary disease and in premature infants. Despite
      great promise, the clinical data comparing the efficacy of MCT-based lipid
      emulsions to their LCT counterparts has been equivocal. This may be due in part
      to the limited nature of the published clinical trials. Measures of efficacy for
      parenteral or enteral nutritional products has taken on new meaning, in light of
      the reported experience using immunomodulatory nutrients. Current concerns about
      cost of medical care and resource use warrant careful deliberation about the
      utility of any new and expensive therapy. Until clinical data can fulfill
      expectations derived from animal studies, it is difficult to advocate the general
      use of MCT-based lipid emulsions. Future clinical studies with MCT-based
      emulsions should have clear outcome objectives sufficient to prove their
      theorized metabolic superiority.

PMID- 8862526
TI  - The dynamics of coiled bodies in the nucleus of adenovirus-infected cells.
AB  - The coiled body is a specific intranuclear structure of unknown function that is
      enriched in splicing small nuclear ribonucleoproteins (snRNPs). Because
      adenoviruses make use of the host cell-splicing machinery and subvert the normal
      subnuclear organization, we initially decided to investigate the effect of
      adenovirus infection on the coiled body. The results indicate that adenovirus
      infection induces the disassembly of coiled bodies and that this effect is
      probably secondary to the block of host protein synthesis induced by the virus.
      Furthermore, coiled bodies are shown to be very labile structures, with a half
      life of approximately 2 h after treatment of HeLa cells with protein synthesis
      inhibitors. After blocking of protein synthesis, p80 coilin was detected in
      numerous microfoci that do not concentrate snRNP. These structures may represent
      precursor forms of the coiled body, which goes through a rapid cycle of
      assembly/disassembly in the nucleus and requires ongoing protein synthesis to
      reassemble.

PMID- 8862528
TI  - Twenty-four-hour energy and nutrient balance in weight stable postobese patients
      after biliopancreatic diversion.
AB  - To better understand the long-term weight stability of postobese patients who
      underwent biliopancreatic diversion (BPD), we studied 24-h energy and nutrient
      balance in eight women at least 3 yr after surgery (PO) and compared the results
      to those obtained in eight normal never-obese control women (C), matched by age
      and weight. Body composition was measured by dual-energy x-ray absorptiometry
      (DXA). All the patients were on an ad libitum diet; 24-h energy and nutrient
      intake were measured on the experimental day. Twenty-four-hour energy expenditure
      (EE) and 24-h nutrient oxidation rates were measured in a respiratory chamber,
      and energy and nutrient balances were calculated after correcting for 24-h fecal
      nutrient loss. No differences in body composition were found between PO and C. PO
      had a higher gross energy intake than C (10.6 +/- 3.4 vs. 8.0 +/- 2.2 MJ/d; p <
      0.05); however, due to the higher energy fecal loss in PO as compared to C (2.4
      +/- 1.3 vs. 0.09 +/- 0.01 MJ/day; p < 0.01), 24-h metabolizable energy intake
      (MEJ) was not different in the two groups. The energy fecal loss in the PO
      patients was mostly in the form of lipid. EE at 24 h was not different in PO as
      compared to C. Therefore energy balance, computed as the difference between 24-h
      MEI and 24-h EE, was similar in the two groups. Respiratory quotient was
      significantly higher in PO than in C (1.00 +/- 0.08 vs. 0.83 +/- 0.03; p < 0.01).
      Carbohydrate (-135 +/- 37 g/d in PO vs. 63 +/- 23 g/d in C; p < 0.001), and lipid
      (48 +/- 14 g/d in PO vs. -23 +/- 6 g/d in C; p < 0.001) balances were different
      in the two groups. We conclude that chronic lipid malabsorption was the main
      metabolic abnormality explaining the achievement of energy balance in postobese
      subjects after biliopancreatic diversion. A chronic reduction of lipid absorption
      seems to play a key role in the long-term weight stability of this group of
      postobese subjects.

PMID- 8862529
TI  - Essential fatty acid deficiency and home total parenteral nutrition patients.
AB  - The requirements for essential fatty acids in patients on home parenteral
      nutrition are not well described. We therefore studied the needs of 12 patients
      receiving parenteral nutrition for at least 4 mo (range: 4 mo-17.3 yr; mean 7.0
      +/- 5.2 yr). Prior to the study, each patient had been receiving intravenous
      lipids either weekly or biweekly and had a triene to tetraene ratio (TTR) on
      plasma phospholipids performed at least annually. A TTR > or = 0.2 was considered
      diagnostic for essential fatty acid deficiency (EFAD). The purpose of this study
      was to determine the required intravenous lipid supplementation in patients on
      home total parenteral nutrition (HTPN). Patients with an initial TTR of < 0.2 had
      their intravenous lipid stopped and changes in their serum phospholipid fatty
      acids were followed every 3-4 wk. Nine of 12 patients had TTRs > 0.2 at some
      point in the study. Phase I consisted of patients who at initiation of the study
      had normal TTRs and were taken off lipid supplementation until their TTR became
      abnormal. Phases II, III, IV, and V consisted of lipid delivered in total
      nutrient admixtures in biweekly doses of 0.6, 1.2, 1.8, and 2.4 g of fat/kg
      bodyweight, respectively. Eight patients normalized their TTRs on the biweekly
      lipid regimens; one patient expired before his ratio normalized; and three
      patients could not be made deficient in essential fatty acids after 26 or more wk
      of fat-free parenteral nutrition. Most patients required 1.2 to 2.4 g of lipid/kg
      bodyweight/biweekly to correct serologic EFAD. The clinical background, as well
      as the length of small bowel remaining, did not seem to identify those patients
      who required lipid supplementation nor the final dose of lipid needed to
      normalize their TTRs.

PMID- 8862530
TI  - The relationship of birthweight with height at 14 and with the growing process.
AB  - The association of birthweight with length at 12 mo and with height at different
      ages was assessed in a sample of 260 healthy adolescents (130 boys and 130
      girls). The longitudinal study included measures on body weight and height at 4,
      6, 12, and 14 yr of age. Birthweight is highly correlated with stature at 14
      years, particularly in male adolescents. Longitudinal principal components
      analysis (LPCA) showed that it is also correlated with the growing process. There
      is also strong evidence that birthweight can be a good predictor of the onset of
      the pubertal maturation process.

PMID- 8862531
TI  - Prealbumin in nutrition evaluation.
AB  - We compressed 16 test-pattern classes of albumin (ALB), cholesterol (CHOL), and
      total protein (TPR) in 545 chemistry profiles to 4 classes by converting decision
      values to a number code to separate malnourished (1 or 2) from nonmalnourished
      (NM) (0) patients, using as cutoff values for nonmalnourished (0), mild (1), and
      moderate (2): ALB 35, 27 g/L; TPR 63, 53 g/L; CHOL 3.9, 2.8 mmol/L; and BUN 9.3,
      3.6 mmol/L. The BUN was found to have too low an S-value to make a contribution
      to the compressed classification. The cutoff values for classifying the data were
      assigned prior to statistical analysis, after examining information in the
      structured data. The data was obtained by a natural experiment in which the test
      profiles routinely done by the laboratory were randomly extracted. The analysis
      identifies the values for the variables used that best classify the data and are
      not dependent on distributional assumptions. The data were converted to 0, 1, or
      2 as outcomes, to create a ternary truth table (each row is nnnn, the n value is
      0 to 2). This allows for 3(4) (81) possible patterns, without the inclusion of
      prealbumin (PAB). The emerging system has much fewer patterns in the information
      rich truth table formed (a purposeful, far from random, event). We added PAB,
      coded, and examined the data for 129 patients. The classes are a compressed truth
      table of n-coded patients with outcomes of 0, 1, or 2 with protein-energy
      malnutrition (PEM) increasing from an all-0 to all-2 pattern. Pattern class (F =
      154), PAB (F = 35), ALB (F = 56), and CHOL (F = 18) were different across PEM
      class and predicted PEM class (R2 = 0.7864, F = 119, p < E-5). Kruskal-Wallis
      analysis of class by ranks was significant for pattern class (1E-18), PAB (6.1E
      15), ALB (1E-16), CHOL (9E-10), and TPR (5.3E-13). The medians and standard error
      (SEM) for PAB, ALB, and CHOL of all four PABCLASSES (NM, mild, moderate, severe)
      are: PAB = 209, 8.7; 159, 9.3; 137, 10.4; 72, 11.1 mg/L, ALB = 36, 0.7; 30.5,
      0.8; 25.0, 0.8; 24.5, 0.8 g/L; CHOL = 4.43, 0.17; 4.04, 0.20; 3.11, 0.21; 2.54,
      0.22 mmol/L. PAB and CHOL values show the effect of nutrition support on PAB and
      CHOL in PEM. Moderately malnourished patients receiving nutrition support have
      PAB values in the normal range at 137 mg/L and at 159 mg/L when the ALB is at 25
      g/L or at 30.5 g/L.

PMID- 8862532
TI  - Gastric emptying, pulmonary function, gas exchange, and respiratory quotient
      after feeding a moderate versus high fat enteral formula meal in chronic
      obstructive pulmonary disease patients.
AB  - High fat enteral formulas have been advocated for the nutritional support of
      chronic obstructive pulmonary disease (COPD) patients because dietary fat
      utilization under ideal conditions produces less CO2 per O2 consumed than
      carbohydrate. No data exist for these patients comparing the effects of a
      moderate fat vs. a high fat enteral formula on gastric emptying times (GE) and
      subsequent CO2 production (VCO2), oxygen consumption (VO2), respiratory quotient
      (RQ), and pulmonary function. Our double-blind crossover study compared these
      parameters after feeding a 355 mL (530 kcal) meal with either 41% fat calories
      (Respalor) or 55% fat calories (Pulmocare). Thirty-six COPD outpatients with a
      forced expiratory volume in 1 s (FEV1) < 60% of predicted were studied after an
      overnight fast. Gastric emptying half-time (GE t1/2) was measured using the 99MTc
      radionuclide technique; VCO2, VO2, RQ, and other pulmonary functions were
      measured at 0, 30, 90, and 150 min postprandial using the Canopy Mode of the
      Deltatrac Metabolic Monitor and the Renaissance Spirometry System. We observed a
      significantly (p = 0.0001) longer GE t1/2 of the high fat meal when compared to
      the moderate fat meal (134.1 vs. 108.6 min) At 30 and 90, but not at 150 min
      postprandial, the VCO2 and VO2 for patients fed the moderate-fat formula were
      significantly (p = 0.05) higher than for those fed the high-fat formula; no
      differences were observed for the other pulmonary functions. Although RQ
      increased significantly (p = 0.01) after both meals, no differences between
      formulas were noted at all postprandial times tested. Compared to the high-fat
      meal, the moderate-fat meal significantly enhanced gastric emptying. The earlier
      rise in VCO2 and VO2 after the moderate-fat meal did not impact pulmonary
      function and reflected the earlier utilization of the moderate-fat meal. The fact
      that RQ was not different between the two meals at all postprandial times tested
      suggest that the higher rise in VCO2 and VO2 after the moderate-fat meal was most
      likely due to earlier gastric emptying of the moderate-fat meal rather than the
      difference of the fat-to-carbohydrate ratio between the two tested meals. The
      impact of these findings on long-term management of COPD patients awaits long
      term prospective studies.

PMID- 8862533
TI  - Growth requirements of endothelial cells in culture: variations in serum and
      amino acid concentrations.
AB  - Endothelial cell growth in vitro is limited to the availability of nutrients from
      commercially available media and added serum. Nutrients, such as amino acids, are
      chiefly derived from the cell culture medium, rather than from added serum, and
      optimal endothelial cell growth may be dependent on amino acid levels in the
      culture media. To test this hypothesis, porcine pulmonary artery-derived
      endothelial cells were exposed to culture medium 199 (M199), amino acid-deficient
      M199 (dM199), as well as dM199 supplemented with amino acids. Cell protein was
      similar in cells cultured for 3 d in M199 supplemented with 1, 3, 5 or 10% bovine
      calf serum, respectively. Addition of amino acid solutions (L-amino acids [Laa],
      DL-amino acids [DLaa], 2Laa, or Laa+glutamine) to dM199 demonstrated a cell
      dependence for optimal growth on the type of amino acids as well as on the total
      available nitrogen in the media. Compared with M199, dM199 supplemented with Laa
      only partially supported long-term growth of endothelial cells in culture. On the
      other hand, dM199 supplemented with either 2Laa, DLaa, or Laa+ glutamine was
      superior over M199 with regard to endothelial cell growth. The addition of
      Laa+glutamine to dM199 was most growth-supporting, with an increase of over 2.6
      fold in total cell protein compared with cells cultured with M199. These results
      suggest that, in addition to the presence of essential amino acids, total
      available nitrogen in culture media may be a critical factor for optimal
      endothelial cell growth.

PMID- 8862534
TI  - Pulmonary embolus as a complication of a central venous catheter.

PMID- 8862536
TI  - Transgene technology and nutrition in the 21st century.

PMID- 8862535
TI  - Inflammation, free radicals, and antioxidants.
AB  - It is becoming increasingly apparent that certain types of inflammatory tissue
      injury are mediated by reactive oxygen metabolites. The most likely sources of
      these oxidizing agents are the phagocytic leukocytes (e.g., neutrophils,
      monocytes, macrophages, and eosinophils) that invade the tissue. These reactive
      radicals and oxidants may injure cells and tissue directly via oxidative
      degradation of essential cellular components as well as injure cells indirectly
      by altering the protease/ antiprotease balance that normally exists within the
      tissue interstitium. It is becoming increasingly apparent that in addition to
      promoting cytotoxicity, reactive oxygen metabolites may also initiate and/or
      amplify inflammation via the upregulation of several different genes involved in
      the inflammatory response, such as those that code for proinflammatory cytokines
      and adhesion molecules. This may occur by the activation of certain transcription
      factors, such as nuclear transcription factor kB (NF-kB). NF-kB is a ubiquitous
      transcription factor and pleiotropic regulator of numerous genes involved in the
      immune and inflammatory response. Essential nutrients such as vitamins C and E
      may protect against oxidant-mediated inflammation and tissue damage by virtue of
      their ability to scavenge free radicals and by their ability to inhibit the
      activation of NF-kB (and possibly other oxidant-sensitive transcription factors).
      Thus, maintaining adequate antioxidant status may provide a useful approach in
      attenuating the cellular injury and dysfunction observed in some inflammatory
      disorders.

PMID- 8862537
TI  - A clinical nutritionist's search for meaning: why should we bother to feed the
      acutely ill, hospitalized patient?

PMID- 8862538
TI  - The nerves, the liver, and the route of feeding: an integrated response to
      nutrient delivery.

PMID- 8862539
TI  - The evolving health care market: professionalism and value at the envelope's
      edge.

PMID- 8862540
TI  - Clinical nutrition: the view from Europe.

PMID- 8862541
TI  - Ensuring the safety and efficacy of extemporaneously prepared infusions.

PMID- 8862543
TI  - Future trends in dietetics: the multiskilled professional.

PMID- 8862542
TI  - Life tables.

PMID- 8862544
TI  - John M. Kinney, MD.

PMID- 8862545
TI  - The active site of carboxypeptidase Taq possesses the active-site motif His-Glu-X
      X-His of zinc-dependent endopeptidases and aminopeptidases.
AB  - Carboxypeptidase (CPase) Taq possesses the His-Glu-X-X-His sequence, which is the
      consensus sequence in the active site of zinc-dependent endopeptidases and amino
      peptidases, at positions 276-280. Amino acid replacement of the conserved His and
      Glu drastically diminished the activity of CPase Taq, and the zinc content of the
      enzyme was also greatly reduced when either of the two His residues was replaced
      with Arg or Tyr. The results indicate that this sequence actually functions as
      the active site in CPase Taq, showing that CPase Taq is a novel type of zinc
      dependent CPase that possesses the His-Glu-X-X-His active-site motif.

PMID- 8862546
TI  - Intrahelical side chain-side chain contacts: the consequences of restricted
      rotameric states and implications for helix engineering and design.
AB  - Intrahelical side chain-side chain (sc-sc) interactions are assumed to play a
      crucial role in the formation and stability of alpha-helices, yet it was found
      that only 37.2% of all helical residues are involved in such close contacts,
      assuming a specific minimum contact distance. The majority (58.0%) of these were
      detected between residues with amino acid sequence spacing i, i + 4. The low
      frequency of intrahelical sc-sc contacts with sequence separations i, i + 1 and
      i, i + 3, each observed with only about one-third of the i, i + 4 counts, can be
      directly and generally attributed to the absence of the g- conformation in
      helices for the dihedral angle chi 1. However, if it was assumed that each side
      chain may maximally make only one sc-sc contact, as most commonly observed, the
      percentage of contacting pairs increased relative to the maximum possible pairs
      for a given sequence spacing by a factor of approximately 4, e.g. from 20.9 to
      81.7% for i, i + 4 contacts. Stereochemical reasons are also given for the
      observation that i, i + 3 contacts are composed largely of ion or polar pairs,
      while hydrophobic residues dominate the i, i + 4 contacts. No significantly
      increased density of intrahelical sc-sc contacts with increasing helix length was
      found. Although there were generally fewer intrahelical contacts between buried
      helical residues when more contacts were made to the tertiary protein
      environment, the number of intrahelical contacts did not increase with increasing
      solvent exposure of the helices. Implications for helix design and the packing of
      helices are discussed.

PMID- 8862547
TI  - Position-dependent protein mutant profile based on mean force field calculation.
AB  - The application of the mean force field in protein mutant stability prediction is
      explored. Based on protein main chain characteristics, including polar fraction,
      accessibility and dihedral angles, the mean force field was constructed to
      evaluate the compatibility between an amino acid residue and its environment,
      from which a position-dependent protein mutant profile was constructed. At each
      position along a protein sequence, the native residue was replaced by the other
      19 types of amino acid residues. The matches were evaluated by energies from mean
      force field calculation, from which a mutant profile along the protein sequence
      was derived. General characteristics of such a profile were analyzed. Mutant
      stabilities for two sets of mutants in two proteins were found to be reasonable
      compared with experimental data, which indicates that the present method can act
      as a guide in protein engineering and as an effective scoring matrix in protein
      sequence-structure alignment studies.

PMID- 8862548
TI  - A molecular dynamics study of the effect of carbon tetrachloride on enzyme
      structure and dynamics: subtilisin.
AB  - Developing enzymes that are functional in highly concentrated halocarbon
      solutions, such as carbon tetrachloride, may prove useful in the development of
      new strategies for environmental remediation and monitoring of pollutant plumes,
      as well as in developing 'green' processes. Doing so will require gaining an
      understanding of the underlying structural and dynamic effects on enzymes induced
      by such solvents. Herein we report a 714 ps molecular dynamics simulation of the
      enzyme subtilisin Carlsberg and its waters of crystallization in a periodic box
      of carbon tetrachloride. The crystal structure from aqueous solution was used as
      the starting structure for our simulation using the AMBER program and forcefield.
      The calculated time-averaged structure is similar to the aqueous X-ray structure
      except for significant differences in loop (or turn) regions, resulting in many
      extra intra-protein hydrogen bonding interactions. Since carbon tetrachloride is
      a non-polar solvent and cannot interact strongly with the protein and water
      molecules, the water molecules stay very close to the protein surface throughout
      the simulation. The mobility of most of the waters was therefore very low. A few
      water molecules underwent significant lateral motion during the simulation, but
      never wandered far from the protein surface. Waters were either hydrogen bonded
      to protein polar groups, other water and/or counterions. Some of the surface
      waters participated in the formation of water-mediated hydrogen bonding networks.
      The increase in total number of intra-protein hydrogen bonds and the formation of
      water-mediated hydrogen bonding networks in carbon tetrachloride is consistent
      with the generally observed increase in thermostability and reduced flexibility
      of proteins in non-aqueous solutions. Several possible carbon tetrachloride
      binding sites on the protein surface are predicted.

PMID- 8862549
TI  - Prediction of the three-dimensional structure of human interleukin-7 by homology
      modeling.
AB  - The three-dimensional structure of human interleukin (IL)-7 has been predicted
      based on homology to human IL-2, IL-4, granulocyte-macrophage colony stimulating
      factor and growth hormone. The model has a topology common to other cytokines and
      displays a unique disulfide pattern. Knowledge of the tertiary structure of IL-7
      has implications for analysis of key binding regions, suggestions for mutagenesis
      experiments and design of (ant)agonists. In this context, the model is discussed
      and compared with other cytokine structures.

PMID- 8862550
TI  - Effect of replacing helical glycine residues with alanines on reversible and
      irreversible stability and production of Aspergillus awamori glucoamylase.
AB  - To decrease irreversible thermoinactivation of Aspergillus awamori glucoamylase,
      five Gly residues causing helix flexibility were replaced with Ala residues.
      Mutation of Gly57 did not affect thermostability. Mutation of Gly137 doubled it
      at pHs 3.5 and 4.5 but barely changed it at pH 5.5. The Gly139-->Ala mutation did
      not change thermostability at pH 3.5, improved it at pH 4.5 and worsened it at pH
      5.5. The Gly 137/Gly139-->Ala/Ala mutation gave 1.5-2-fold increased
      thermostabilities at pHs 3.5-5.5. Mutations of Gly251 and Gly383 decreased it at
      all pHs. Gly137-->Ala and Gly137/Gly139-->Ala/Ala glucoamylases are the most
      stable yet produced by mutation. Guanidine treatment at pH 4.5 decreased the
      reversible stabilities of Gly137-->Ala, Gly139-->Ala and Gly137/Gly139-->Ala/Ala
      glucoamylases at infinite dilution while not changing those of Gly251-->Ala and
      Gly383-->Ala glucoamylases, which is, in general, opposite to what occurred with
      thermoinactivation. Mutation of Gly57 greatly improved the extracellular
      glucoamylase production by yeast, that of Gly137 barely affected it and those of
      Gly139 and of both Gly137 and Gly139 strongly impeded it. These observations
      suggest that alpha-helix rigidity can affect reversible and irreversible
      glucoamylase stability differently, that the effects of multiple mutations within
      one alpha-helix to improve stability are not always additive and that even single
      mutations can strongly affect extracellular enzyme production.

PMID- 8862551
TI  - Analysis of the catalytic mechanism of a fungal lipase using computer-aided
      design and structural mutants.
AB  - Both an active enzyme conformation and stabilization of tetrahedral transition
      states are essential for the catalysis of ester bond hydrolysis by lipases. X-ray
      structural data and results from site-directed mutagenesis experiments with
      proteases have been used as a basis for predictions of amino acid residues likely
      to have key functions in lipases. The gene encoding a lipase from Rhizopus oryzae
      was cloned and expressed in Escherichia coli. Site-directed mutagenesis of this
      gene was used to test the validity of computer-aided predictions of the
      functional roles of specific amino acids in this enzyme. Examination of the
      kinetic constants of the Rhizopus oryzae lipase variants allowed us to identify
      amino acid residues which are directly involved in the catalytic reaction or
      which stabilize the active geometry of the enzyme. The combination of these
      results with molecular mechanics simulations, based on a homology-derived
      structural model, provided new information about structure-function
      relationships. The interpretation of the data is consistent with results obtained
      with other hydrolases, such as proteases.

PMID- 8862552
TI  - The role of Glu87 and Trp89 in the lid of Humicola lanuginosa lipase.
AB  - The importance of Glu87 and Trp89 in the lid of Humicola lanuginosa lipase for
      the hydrolytic activity at the water/lipid interface was investigated by site
      directed mutagenesis. It was found that the effect on the hydrolytic activity
      upon the replacement of Trp89 with Phe, Leu, Gly or Glu was substrate dependent.
      The Trp89 mutants displayed an altered chain length specificity towards
      triglycerides, with a higher relative activity towards triacetin and trioctanoin
      compared with tributyrin. Trp89 was shown to be less important in the hydrolysis
      of vinyl esters compared with ethyl esters and triglycerides. An exclusive effect
      on the acylation reaction rate by the mutation of Trp89 was consistent with the
      data. It is suggested that Trp89 is important in the process of binding the acyl
      chain of the substrate into the active site for optimal acylation reaction rate.
      The Trp89Phe mutation resulted in an increased hydrolytic activity towards 2
      alkylalkanoic acid esters. This is suggested to be due to reduction of
      unfavourable van der Waals contacts between Trp89 and the 2-substituent of the
      substrate. Thus, in contrast to natural substrates, Trp89 has a negative impact
      on the catalytic efficiency when substrates with bulky acyl chains are used. In
      contrast to the Trp89 mutations, the effect on the hydrolytic activity of the
      Glu87Ala mutation was almost substrate independent, 35-70% activity of wild-type
      lipase. A reduction of both the acylation and deacylation reaction was consistent
      with the data.

PMID- 8862553
TI  - Autocatalytic processing of pro-papaya proteinase IV is prevented by crowding of
      the active-site cleft.
AB  - The DNA coding for pro-papaya proteinase IV (PPIV) has been cloned and expressed
      in Escherichia coli. Heterologous expression of the protein, followed by
      refolding in vitro, yields an enzymatically active pro-enzyme which fails to
      autodigest to form the mature protein. Mutagenesis of the active site of papain
      to simulate that of PPIV yields a proenzyme which also fails to autoactivate.
      Complementary mutagenesis of the pro-region/mature boundary of PPIV, to introduce
      its own substrate recognition sequence, has, however, produced a pro-enzyme that
      will autocatalytically cleave. This is the first report of enzymatic activity in
      a recombinant pro-cysteine proteinase, and the first time that such a protein has
      been shown to fail to autocatalytically cleave because of its stringent substrate
      specificity.

PMID- 8862554
TI  - Single antibody domains as small recognition units: design and in vitro antigen
      selection of camelized, human VH domains with improved protein stability.
AB  - Folding stabilities of camelized human antibody VH domains were studied through
      the determination of their melting points in thermodenaturation experiments. The
      melting point of a VH domain originating from a synthetic library of human VHs,
      which had been optimized for the use as small recognition units through the
      mimicking of camelid antibody heavy chains occurring naturally without light
      chain, was 56.6 degrees C compared with 71.2 degrees C of the original human VH.
      Its stability was improved (melting point 61.6 degrees C) through three mutations
      to mimic camelid VHs even further: Va137 was replaced by phenylalanine and two
      cysteines were introduced at position 33 and 100b. The resulting VH folded
      properly and formed a second intradomain disulphide between the extra cysteines.
      The new mutations were then built constitutively into a phage-display VH library,
      from which antigen-specific VHs were selected. Two were analysed for stability
      with melting points of 72.6 and 75.3 degrees C. Thus secondary camelization
      enabled the isolation of VHs with improved folding stabilities exceeding even
      that of the original human VH. This indicates an effect on folding stability for
      some mutations specific in the light chain lacking camelid heavy chains.

PMID- 8862555
TI  - Complementarity determining region residues aspartic acid at H55, serine at H95
      and tyrosines at H97 and L96 play important roles in the B72.3 antibody-TAG72
      antigen interaction.
AB  - Structural analysis derived from the crystallographic study of the chimeric B72.3
      antibody illustrated some major atomic interactions between complementarity
      determining region (CDR) residues. For example, hydrogen bonds are formed between
      H35/H95, L50/H97, H53/H55 and H96/L96 respectively. These CDR residues may play
      important roles in the B72.3-TAG72 (antibody-antigen) interaction either by
      direct interaction with the TAG72 antigen or by maintaining a CDR loop
      conformation through atomic interactions between CDR residues. In order to
      confirm these assumptions, we altered these CDR residues by site-directed
      mutagenesis and determined binding affinities of these mutant chimeric antibodies
      for the TAG72 antigen in a solid-phase radioimmunoassay. We found that H55, H95,
      H97 and L96 are important CDR residues for the B72.3-TAG72 interaction. Single
      amino acid substitutions of aspartic acid and serine by alanine at H55 of CDR2
      and at H95 of CDR3 respectively and of tyrosine by phenylalanine at H97 and L96
      of CDR3, significantly reduced the binding affinity for the TAG72 antigen by 20-,
      8-, 16- and 45-fold respectively. Therefore, this study reveals some of the
      requirements for maintaining the integrity of the B72.3 antibody combining sites.

PMID- 8862556
TI  - Construction, properties and specific fluorescent labeling of a bovine
      prothrombin mutant engineered with a free C-terminal cysteine.
AB  - To define the role of phosphatidylserine-induced conformational changes in
      prothrombin activation during blood coagulation, a recombinant bovine prothrombin
      was constructed, characterized and shown to have a globally native-like
      conformation. We introduced a cysteine to replace the penultimate residue
      (Gly581) of a previously constructed active site mutant, and expressed the double
      mutant in Chinese hamster ovary cells at the level of 0.6 microgram/ml of cell
      culture medium. Specific labeling with fluorescein maleimide was accomplished by
      limited reduction with dithiothreitol to free the engineered cysteine while
      maintaining the native-like functional properties of the molecule. The average
      stoichiometry of labeling was 0.84 probe/protein. The location of the probe at
      the C-terminus was confirmed by proteolysis by native thrombin, by Taipan venom,
      and by carboxypeptidase Y. Both the double mutant and labeled prothrombin could
      be activated by snake venoms and the prothrombinase but, as expected, the double
      mutant meizothrombin did not autolyze as does native meizothrombin. Thus, for the
      first time, a native-like but specifically labeled prothrombin has been
      constructed. This molecule will be an essential tool for elucidating the
      structural role of membranes during prothrombin activation. In addition, the
      methods described might be usefully applied to labeling of an odd, engineered
      cysteine in other disulfide bond-containing proteins.

PMID- 8862557
TI  - Neutralizing antibodies to Escherichia coli Vero cytotoxin 1 and antibodies to
      O157 lipopolysaccharide in healthy farm family members and urban residents.
AB  - An enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Escherichia
      coli O157 lipopolysaccharide (LPS) was developed with sera from 63 children with
      confirmed recent E. coli O157 infection and from 256 age-stratified urban
      controls. The median ELISA values for control and case sera were 0.05
      (interquartile range, 0 to 0.20; mean +/- standard deviation [SD], 0.15 +/- 0.22)
      and 1.41 (interquartile range, 1.11 to 1.59; mean +/- SD, 1.41 +/- 0.53),
      respectively (P < 0.001). With a breakpoint of 0.59 (mean ELISA value of the
      control sera + 2 SDs), the assay had a sensitivity, specificity, and positive and
      negative predictive values of 95, 94, 80, and 98%, respectively, for recent E.
      coli O157 infection. The O157 LPS assay and Vero cytotoxin (VT) 1-neutralizing
      antibody (NAb) assay were used to compare the relative frequencies of O157 LPS
      antibodies and VT1-NAbs in an age-stratified urban population from Toronto,
      Ontario, Canada, and in 216 healthy family members from dairy farm in southern
      Ontario. The frequency of O157 LPS antibodies was about threefold higher in dairy
      farm residents (12.5%) than in urban residents (4.7%) (P < 0.01). Similarly, the
      frequency of VT1-NAbs was about sixfold higher in dairy farm residents (42.0%)
      than in urban residents (7.7%) (P < 0.001). These findings are consistent with a
      greater level of exposure of dairy farm residents to VT-producing E. coli (VTEC)
      strains. The high rate of seropositivity to VT1 in farm residents probably
      reflects the booster effect of repeated VTEC exposures and argues against a
      sustained generalized immunosuppressive effect of VT1. Seroepidemiological
      studies may help in assessing the level of exposure of different populations to
      VTEC strains.

PMID- 8862558
TI  - Differentiation of spotted fever group rickettsiae by sequencing and analysis of
      restriction fragment length polymorphism of PCR-amplified DNA of the gene
      encoding the protein rOmpA.
AB  - Currently, the genotypic identification of the spotted fever group (SFG)
      rickettsiae is based on restriction fragment length polymorphism analysis of PCR
      amplified genes coding for the enzyme citrate synthase and the surface proteins
      rOmpA and rOmpB. A set of useful restriction endonucleases was found following
      comparison of Rickettsia rickettsii and R. prowazekii sequences. However, by
      using three PCR amplifications and four enzyme digestions with this set, it was
      impossible to differentiate between all of the known serotypes of the SFG
      rickettsiae. We amplified by PCR and sequenced using an automated laser
      fluorescent DNA sequencer a fragment of the gene encoding the protein rOmpA from
      21 serotypes of the SFG rickettsiae. A 632-bp amplification product was obtained
      for most of the strains, although no product could be obtained by using R. akari,
      R. australis, R. helvetica, and R. bellii DNAs. We found a characteristic
      sequence for all strains studied except the two isolates of R. massiliae,
      isolates GS and Mtul. Using the software package BISANCE, we determined the
      restriction map of this fragment and identified five potentially useful
      endonucleases, RsaI, AluI, PstI, XbaI, and AvaII. We confirmed the computer
      analysis-derived profiles by PCR-restriction fragment length polymorphism
      analysis. The combination of the profiles obtained after digestion of the PCR
      product by RsaI and PstI allowed for the differentiation of 16 strains. The use
      of AluI and XbaI allowed for the characterization of R. parkeri and strain HA-91,
      respectively. R. africae and strain S were differentiated by AvaII digestion.
      Thus, using a single PCR amplification, we were able to differentiate all of the
      SFG rickettsiae whose ompA gene was amplified by PCR.

PMID- 8862559
TI  - Molecular epidemiology of Mycobacterium bovis in Texas and Mexico.
AB  - Seventy-nine Mycobacterium bovis isolates recovered from Mexican and Texas cattle
      were categorized into 16 and 25 distinct types on the basis of IS6110 and direct
      repeat fingerprint patterns, respectively. By using a combination of both
      fingerprint patterns, 30 distinct restriction fragment length polymorphism types
      were defined. Fifty-eight of 79 isolates (73%) were distributed among nine
      clusters. Clustered isolates were identified within herds, as well as in
      geographically disperse herds in Texas and Mexico. This observation is consistent
      with active transmission within herds and among herds, presumably as a result of
      active or historical cattle movements. The majority of bovine isolates (64 of 79)
      exhibited a single copy of IS6110. Interestingly, in contrast to previous
      studies, a high percentage of bovine isolates (15 of 79) exhibited multiple
      IS6110 copies (two to five) distributed among 11 different restriction fragment
      length polymorphism types. It is speculated that transmission from noncattle
      sources may be responsible. Continued fingerprinting of isolates originating from
      nonbovine sources and herd surveys is expected to provide useful information
      regarding the epidemiology of tuberculosis in this region.

PMID- 8862560
TI  - Isolation of methicillin-resistant coagulase-negative staphylococci from
      chickens.
AB  - Methicillin-resistant coagulase-negative staphylococci were isolated from the
      nares and skin of 1- to 8-week-old healthy chickens in three flocks from a farm.
      Isolation of methicillin-resistant coagulase-negative staphylococci was positive
      for 72 (25.7%) of the 280 chickens tested, with the frequency varying from 2.2 to
      100% according to flock. A total of 45 appropriate isolates were selected and
      subjected to identification. Of the 45 methicillin-resistant coagulase-negative
      staphylococcal isolates selected, 37 were identified as Staphylococcus sciuri, 5
      were identified as Staphylococcus epidermidis, and 3 were identified as
      Staphylococcus saprophyticus. The distribution of the species was different among
      the flocks. Comparative analysis of the SmaI-digested chromosomal DNA by pulsed
      field gel electrophoresis revealed that the isolates could have originated from a
      single clone of each of S. sciuri and S. saprophyticus and three clones of S.
      epidermidis. By two methods based on the PCR technique, the mecA gene was
      detected in all five representative isolates of each methicillin-resistant
      coagulase-negative staphylococcal clone. The nucleotide sequence of a PCR
      fragment obtained from an isolate of S. sciuri was completely identical to the
      corresponding region of mecA genes reported in human methicillin-resistant
      Staphylococcus aureus isolates and Staphylococcus epidermidis isolates. The
      representative methicillin-resistant coagulase-negative staphylococcal isolates
      were resistant to many beta-lactam antibiotics, and some isolates were also
      resistant to macrolide and aminoglycoside antibiotics. This is the first evidence
      of the existence of methicillin-resistant coagulase-negative staphylococci from
      animals possessing the mecA gene.

PMID- 8862561
TI  - Detection by PCR of the nim genes encoding 5-nitroimidazole resistance in
      Bacteroides spp.
AB  - A PCR method was developed for detection of the nim genes encoding 5
      nitrolmidazole resistance in Bacteroides spp. Two PCR primers specific for nim
      genes were designed. They allowed amplification of a 458-bp fragment from all
      characterized plasmid- and chromosome-borne metronidazole resistance genes. The
      specificity of the method was tested with DNA from metronidazole-sensitive
      Bacteroides spp. strains and from other strains of unrelated species. Each DNA
      preparation was analyzed with and without an internal positive control to verify
      that the absence of PCR amplification product was not due to inhibition of the
      Taq polymerase inhibitors. By this technique, two newly discovered metronidazole
      resistant clinical strains of Bacteroides fragilis were shown to harbor
      resistance genes undetectable by Southern blotting. In spite of the sequence
      divergence of the nim genes, the PCR method is thus suitable for epidemiological
      investigations. The amplification method also revealed that nim-related
      resistance genes were not present in either Streptomyces strain S6670, a natural
      producer of 2-nitroimidazole, or in Enterococcus faecalis strains, which have
      been suggested to possess metronidazole-inactivating enzyme.

PMID- 8862562
TI  - Monitoring of cytomegalovirus infection and disease in bone marrow recipients by
      reverse transcription-PCR and comparison with PCR and blood and urine cultures.
AB  - Preemptive therapy is a promising strategy for the prevention of serious
      cytomegalovirus (CMV) disease after bone marrow (BM) transplantation but requires
      relevant diagnostic tests. We compared the clinical value of a reverse
      transcription (RT)-PCR method, which detected a late viral mRNA in peripheral
      blood leukocytes (PBL), with a PCR method that detected the viral DNA in PBL and
      with viral culture from leukocytes and urine for the diagnosis of symptomatic CMV
      infection after BM transplantation. Forty-five consecutive BM recipients were
      prospectively tested at weekly intervals by the four methods. CMV infection,
      demonstrated either by the culture of CMV or by repeated detection of viral DNA,
      was observed in 28 patients, but only 14 developed CMV-related clinical symptoms.
      The clinical sensitivity and specificity of each technique for detection of
      symptomatic infection were, respectively, 36 and 74% for urine culture, 43 and
      84% for leukocyte culture, 100 and 65% for PCR, and 71 and 94% for RT-PCR.
      Although PCR detection of DNA in PBL was the earliest and most sensitive
      technique for the diagnosis of CMV infection, RT-PCR was more predictive of the
      onset of CMV-related clinical symptoms. These data suggest that both molecular
      methods should be used for identifying BM recipients at highest risk of CMV
      disease.

PMID- 8862563
TI  - Patient-to-patient spread of a single strain of Corynebacterium striatum causing
      infections in a surgical intensive care unit.
AB  - Over a 12-month period, Corynebacterium striatum strains were isolated from
      clinical specimens from 14 patients admitted to a surgical intensive care unit.
      These isolates were identical by morphology and biotype and displayed the same
      antibiogram. Ten isolates were found to be the sole possible pathogen. These 10
      isolates were from six patients, three of whom had signs of infection at the time
      of positive culture. Further typing was performed by random amplification of
      polymorphic DNA analysis, by which all strains were identical and were found to
      differ to various degrees from reference strains and from isolates found in
      clinical samples from other wards. In a case-control study the only independent
      risk factor for acquiring the strain was intubation for longer than 24 h (odds
      ratio, 20.09; 95% confidence interval, 2.29 to 176.09). The same strain was
      isolated from surfaces and from air sampled in the direct vicinity of infected
      patients but never from surfaces or air in other places of the ward. The strain
      was not isolated from the ventilators. The strain was cultured from the hands of
      personnel attending to infected patients, but no long-term carriers were found
      among members of the hospital personnel, suggesting transient carriage only. We
      conclude that C. striatum can cause serious nosocomial infections in surgical
      intensive care unit patients and may spread from patient to patient via the hands
      of attending personnel.

PMID- 8862564
TI  - Use of multiple PCR primer sets for optimal detection of human papillomavirus.
AB  - Using multiple PCR primer sets, we tried to optimize the detection of human
      papillomavirus (HPV) in DNA samples isolated from 361 frozen biopsy specimens
      from patients with invasive cervical carcinomas. The HPVs detected were placed
      into three distinct groups, including group I/Inex at Telelab (Skien, Norway) and
      group Ineg and group II at the Norwegian Radium Hospital (Oslo, Norway). The
      consensus primer sets were Oli-1b-oli-2i, My09-My11, Gp5-Gp6, and Gp(5+)-Gp6+
      from the HPV L1 gene and CpI-CpIIG from the E1 gene. Using these consensus
      primers together with the type-specific primers from E6-E7, we found that 355
      patients (98%) were HPV positive. Type-specific primers for HPV types 11, 16, 18,
      31, 33, and 35 detected more HPV-infected patients than the most sensitive
      consensus primer set, while the three consensus primer sets My, Gp/Gp+, and Cp
      together detected more HPV-positive patients than the type-specific primers.
      Testing of sensitivity of the PCR with SiHa cells serially diluted in lymphocytes
      (HPV-negative cells) indicated a detection limit of 6,300 HPV type 16 DNA copies
      with consensus primers (My, Gp+, and Cp) and 126 original HPV type 16 DNA copies
      with type-specific primers. Comparison of the amplification results for consensus
      L1 primers and type-specific E6-E7 primers indicated the presence of L1 deletions
      in 23 of 56 samples. The conclusion is that in PCR detection systems, multiple
      consensus primers and type-specific primers should be used in order to detect all
      patients harboring HPV.

PMID- 8862565
TI  - Isolation of canine parvovirus from a cat manifesting clinical signs of feline
      panleukopenia.
AB  - Twenty-seven feline parvovirus (FPV) isolates were recovered from cats clinically
      diagnosed with feline panleukopenia (FPL) for assessing antigenic and genomic
      properties of FPL viruses (FPLV) recently prevalent among cats in Japan. All
      isolates, with the exception of one novel isolate, FPV-314, possessed homologous
      properties, and their subgroups in FPVs were identified as FPLV. The FPV-314
      isolate, which was from a 1.5-year-old cat which manifested clinical signs of FPL
      and died on the 13th day after the first medical examination, was finally
      identified as canine parvovirus (CPV) because it lacked a specific antigenic
      epitope commonly detected in FPLV and mink enteritis virus and because the
      nucleotide sequence of the capsid protein gene was almost identical to those of
      CPV-2a and -2b antigenic type strains recently prevalent among dogs in Japan. The
      present result together with our previous findings (M. Mochizuki, R. Harasawa,
      and H. Nakatani. Vet. Microbiol. 38:1-10, 1993) indicates the possibility that
      CPV and FPLV undergo mutual interspecies transmission between dogs and cats, and
      it is postulated that they may cause disease in some adventitious hosts.

PMID- 8862566
TI  - Candida albicans serotype analysis by flow cytometry.
AB  - Candida albicans strains can be assigned to either of two major serogroups, A or
      B. Antigenic surface determinants present only in serotype A strains allow such a
      distinction, which has epidemiologic relevance. Reports have established that the
      relative distributions of the two serotypes can vary depending on the geographic
      origin of the isolates. A prevalence of susceptibility to an antifungal agent,
      flucytosine, was also observed with isolates of serotype A. More recently, it was
      suggested that the occurrence of serotype B isolates in various clinical forms of
      candidiasis is increasing. However, this latest finding remains controversial
      since serotyping results vary widely from one laboratory to another because of
      the lack of standardized methodologies. Difficulty in interpretation of results,
      which may lead to erroneous serotype identification, is the major setback
      associated with current methods. For this study, we thus devised a procedure that
      relies on flow cytometry and that may eliminate ambiguities in serotype
      determination. The validation of results was achieved with two types of serotype
      A-specific antisera, Iatron Factor 6 antiserum and an anti-C. albicans antiserum
      adsorbed on serotype B yeast cells. Agreement between results obtained with these
      two reagents was 100% with a wide array of Candida strains. These results
      confirmed the potential of the flow cytometric procedure as a reliable and
      reproducible method to establish the serotypes of C. albicans strains.
      Furthermore, some applications of this procedure to the epidemiological study of
      this human pathogen are presented.

PMID- 8862567
TI  - Rapid diagnosis of adenoviral conjunctivitis by PCR and restriction fragment
      length polymorphism analysis.
AB  - To detect and identify adenovirus (Ad), we used a combination of PCR and
      restriction fragment length polymorphism (RFLP) analysis. Nested PCR with two
      primer sets that hybridize to the conserved region for hexon proteins of 14
      prototypes of Ad, Ad serotype 1 (Ad1) to Ad8, -11, -14, -19, -37, -40, and -41,
      amplified a 956-bp DNA fragment. The amplified fragments from the 14 prototypes
      were completely differentiated with a combination of three restriction
      endonucleases, EcoT14I, HaeIII, and HintI. We applied this new method for 127
      samples of conjunctival scrapings from patients with conjunctivitis and compared
      the results with those obtained with the combination of culture isolation and a
      neutralization test (NT). PCR gave a positive result in 69 of 127 cases (54.3%),
      while only 61 of the 127 samples (48.0%) tested positive by culture isolation.
      Compared with isolation, the PCR method had a sensitivity of 100% (61 of 61).
      Positive PCR samples were further classified as Ad37 (59.5%), -3(31.9%), -11
      (4.3%), -8 (2.9%), and -4 (1.4%) by PCR-RFLP analysis. Of eight samples that were
      PCR positive and culture isolation negative, six were Ad37 and two were Ad8 by
      PCR-RFLP analysis. These differentiations of isolation-positive samples were
      identical to the results obtained by the NT. It took only 3 days to detect and
      identify Ad by PCR-RFLP analysis, whereas it took at least 3 weeks by culture
      isolation and NT. Our newly developed method of detecting and typing human Ad by
      PCR-RFLP analysis is more sensitive, accurate, and rapid than the conventional
      method of culture isolation and an NT.

PMID- 8862568
TI  - Microwell hybridization assay for detection of PCR products from Mycobacterium
      tuberculosis complex and the recombinant Mycobacterium smegmatis strain 1008 used
      as an internal control.
AB  - A microwell hybridization assay was developed for the detection of the PCR
      products from both Mycobacterium tuberculosis complex bacteria and the
      recombinant Mycobacterium smegmatis strain 1008 that is used as an internal
      control to monitor inhibition in the PCR based on the M. tuberculosis complex
      specific insertion sequence IS6110. The test is based on specific detection with
      digoxigenin-labeled oligonucleotide probes of biotinylated PCR products which are
      captured in a microtiter plate coated with streptavidin. The captured PCR
      products are hybridized separately with two probes, one specific for the PCR
      product from IS6110 from M. tuberculosis complex and the other specific for the
      PCR fragment from the modified IS6110 fragment from the recombinant M. smegmatis
      1008. The microwell hybridization assay discriminates perfectly between the two
      types of amplicon. The amount of PCR product that can be detected by this assay
      is 10 times less than that which can be detected by agarose gel electrophoresis.
      The test can be performed in 2 h. It is much faster and less laborious than
      Southern blot hybridization. Furthermore, the interpretation of results is
      objective. The assay was used with 172 clinical samples in a routine microbiology
      laboratory, and the results were in complete agreement with those of agarose gel
      electrophoresis and Southern blot hybridization.

PMID- 8862569
TI  - Methicillin-resistant Staphylococcus aureus isolates recovered from a New York
      City hospital: analysis by molecular fingerprinting techniques.
AB  - Fifty-five methicillin-resistant Staphylococcus aureus (MRSA) isolates collected
      at New York Hospital Medical Center of Queens in 1989 were analyzed by molecular
      fingerprinting techniques. Close to 70% of these isolates (38 of 55) shared a
      common pulsed-field gel electrophoretic pattern, carried the same mecA gene
      polymorph type II, were free of the transposon Tn554, and would not react with a
      mecI-specific gene probe. An additional five isolates shared all properties of
      the major MRSA clone except that they carried mecA gene polymorph type III. All
      these isolates had an extremely heterogeneous methicillin resistance phenotype
      that belonged to population analysis profile class 1 or 2. The rest of the 12
      MRSA isolates showed a variety of chromosomal pulsed-field gel electrophoretic
      patterns that carried different mecA polymorphs and that also gave positive
      reactions with DNA probes for Tn554 and for the mecI gene. The molecular features
      of the majority MRSA clone suggest that it is an archaic MRSA isolate similar in
      features to early MRSA isolates recovered in the 1960s.

PMID- 8862570
TI  - Substances interfering with direct detection of Mycobacterium tuberculosis in
      clinical specimens by PCR: effects of bovine serum albumin.
AB  - Interfering substances have been reported to inhibit PCR assays for the direct
      detection of Mycobacterium tuberculosis in clinical specimens. Using an internal
      control, we determined that 52% of respiratory specimens interfered with our PCR
      assay. On the basis of these findings, we tried to circumvent the problem by
      simply diluting prepared sediments. With sediment from a routinely processed
      sputum known to be inhibitory to PCR, one aliquot was prepared in a routine
      manner for PCR. Remaining sediment was diluted in phosphate-buffered saline,
      Middlebrook 7H10 broth, or BACTEC 12B broth; an internal control was added to all
      reaction mixtures and controls. Internal control was detected only in the sample
      diluted with BACTEC 12B medium. Components of the BACTEC 12B medium including
      PANTA reagent (polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and
      azlocillin), reconstituting fluid, 0.2% glycerol, 0.05% Tween 80, and 0.05%
      bovine serum albumin (BSA) were tested in a similar manner. Only 0.05% BSA
      resulted in amplification of the internal control DNA. Varying concentrations of
      BSA were added to 11 aliquots of a respiratory sediment known to be inhibitory to
      the PCR. Internal control was detected in all reaction mixtures containing
      0.00038 to 0.1% BSA. To determine the ability of BSA to override inhibition,
      respiratory specimens were run in triplicate: undiluted, diluted 1:2 with BACTEC
      12B medium, or diluted with 0.026% BSA. For 21 of 22 inhibitory specimens, BSA
      was able to override the presence of interfering substances. These data suggest
      that the presence of BSA in a PCR assay is critical for the direct detection of
      M. tuberculosis in respiratory specimens.

PMID- 8862571
TI  - Use of in-house studies of molecular epidemiology and full species identification
      for controlling spread of vancomycin-resistant Enterococcus faecalis isolates.
AB  - Infection with multidrug-resistant (MDR) organisms is a major clinical challenge,
      and few, if any, therapeutic options remain available. Increasingly, infection
      control measures have taken on greater importance in preventing the nosocomial
      transmission of MDR organisms. During December 1994 and January 1995, we
      identified a cluster of vancomycin-resistant Enterococcus faecalis isolates
      involving 16 patients situated in different areas of our university-affiliated
      teaching hospital. Initial review of laboratory requisition forms for the
      patients' locations revealed no common association, suggesting that the
      occurrence was not due to horizontal spread. However, using genomic DNA
      extraction, restriction enzyme analysis, and gel electrophoresis, we found that
      12 patients were infected with isolates originating from a single clone, 2 other
      patients were infected with isolates from a different clone, and the remaining 2
      patients were infected with unique strains. Because the typing data suggested
      nosocomial spread, chart review was undertaken to determine a possible common
      exposure source. With three exceptions, clonal isolates were linked to patient
      movement between surgical floors, intensive care units, and a rehabilitation
      unit. A detailed review of patient records revealing the association would not
      have been performed without realization of clonality. Thus, the data demonstrate
      the utility of genomic typing for epidemiological purposes. In turn, targeted
      infection control measures that halted the spread of the potentially lethal MDR
      pathogen were instituted.

PMID- 8862573
TI  - Thin agar film for enhanced fungal growth and microscopic viewing in a new
      sealable fungal culture case.
AB  - This project was undertaken to find ways to enhance fungus colony maturation, to
      make viewing of fungal cultures easier, and to reduce disruption of the fungal
      structures to be observed for identification. Accordingly, a technique using a
      thin (0.2-mm) agar film that avoids problems inherent in traditional methods of
      fungal culture and identification was developed. In addition, to accommodate the
      0.2-mm layer of agar film and a contiguous thicker 4-mm section of agar, a
      sealable fungal culture case that fits within microscope stage calipers and under
      the objective lenses was invented. The growth and identification of 28 organisms
      were evaluated in the sealable fungal culture cases and on double-pour agar
      plates by using potato dextrose agar in both. Compared with results obtained with
      the double-pour agar plates (rated as "good"), fungal growth and identification
      with the sealable fungal culture case were superior (rated as "excellent") (P <
      0.05, chi-square test). The thin agar film limits excessive mycelial growth,
      while it often promotes complete sporulation or other forms of maturation of the
      fungal colony. More importantly, the thin agar film allows direct microscopic
      viewing of the developing fungal colonies. The portion of the sealable fungal
      culture case with the 4-mm layer of agar can be used for evaluation of colony
      pigment and texture. In conclusion, this new sealable fungal culture case allows
      direct viewing and earlier fungal species identification with greater intrinsic
      safety.

PMID- 8862572
TI  - Ehrlichia canis-like agent isolated from a man in Venezuela: antigenic and
      genetic characterization.
AB  - We report the first isolation and molecular and antigenic characterization of a
      human ehrlichial species in South America. A retrospective study was performed
      with serum specimens from 6 children with clinical signs suggestive of human
      ehrlichiosis and 43 apparently healthy adults who had a close contact with dogs
      exhibiting clinical signs compatible with canine ehrlichiosis. The evaluation was
      performed by the indirect fluorescent-antibody assay with Ehrlichia chaffeensis
      Arkansas, Ehrlichia canis Oklahoma, and Ehrlichia muris antigens. The sera from
      two apparently healthy humans were positive by the indirect fluorescent-antibody
      assay for all three antigens. Of the three antigens, samples from humans 1 and 2
      showed the highest antibody titers against E. chaffeensis and E. muris,
      respectively. The remaining serum samples were negative for all three antigens.
      One year later examination of a blood sample from subject 1 revealed morulae
      morphologically resembling either E. canis, E. chaffeensis, or E. muris in
      monocytes in the blood smear. The microorganism, referred to here as Venezuelan
      human ehrlichia (VHE), was isolated from the blood of this person at 4 days after
      coculturing isolated blood leukocytes with a dog macrophage cell line (DH82). The
      organism was also isolated from mice 10 days after intraperitoneal inoculation of
      blood leukocytes from subject 1. Analysis by electron microscopy showed that the
      human isolate was ultrastructurally similar to E. canis, E. chaffeensis, and E.
      muris. When the virulence of VHE in mice was compared with those of E.
      chaffeensis, E. canis, and E. muris, only VHE and E. muris induced clinical signs
      in BALB/c mice at 4 and 10 days, respectively, after intraperitoneal inoculation.
      VHE was reisolated from peritoneal exudate cells of the mice. Only E. chaffeensis
      and E. muris-infected mice developed significant splenomegaly. Western
      immunoblot analysis showed that serum from subject 1 reacted with major proteins
      of the VHE antigen of 110, 80, 76, 58, 43, 35, and 34 kDa. Human serum against E.
      chaffeensis reacted strongly with 58-, 54-, 52-, and 40-kDa proteins of the VHE
      antigen. Anti-E. canis dog serum reacted strongly with 26- and 24-kDa proteins of
      VHE. In contrast, anti-E. sennetsu rabbit and anti-E. muris mouse sera did not
      react with the VHE antigen. Serum from subject 1 reacted with major proteins of
      90, 64, or 47 kDa of the E. chaffeensis, E. canis, and E. muris antigens. This
      reaction pattern suggests that this serum sample was similar to serum samples
      from E. chaffeensis-infected human patients in Oklahoma. The base sequence of the
      16S rRNA gene of VHE was most closely related to that of E. canis Oklahoma. On
      the basis of these observations, we suggest that VHE is a new strain or a
      subspecies of E. canis which may cause asymptomatic persistent infection in
      humans.

PMID- 8862574
TI  - Immunoblot assay using excreted-secreted antigens of Trypanosoma cruzi in
      serodiagnosis of congenital, acute, and chronic Chagas' disease.
AB  - Immunoblotting with trypomastigote excreted-secreted antigens (TESA blot) of
      Trypanosoma cruzi was evaluated as a method for diagnosis of chronic and acute
      phases as well as congenital (in newborn children) Chagas' disease. Serum samples
      from acute-phase and congenital infections were considered to be positive when
      they reacted with ladder-like bands of 130- to 200-kDa antigens, recognized by
      immunoglobulin M (IgM) and IgG antibodies, while IgG from chronic-phase sera
      recognized a broad band antigen of 150 to 160 kDa. Nonchagasic sera were not
      reactive to these antigens. The study was carried out on 512 patients, 111 of
      whom were nonchagasic but included cases of leishmaniasis or other pathologies,
      and 401 chagasic patients. The latter group comprised 361 chronic cases, 36 acute
      cases, and 4 congenital cases in newborn children. Among the chronic cases, 256
      were from areas in which T. cruzi is endemic but which differed widely in the
      pathogenic expression of T. cruzi infection and in parasitemia levels. These
      patients at the same time showed a broad range of low, medium, and high
      reactivity to conventional enzyme-linked immunosorbent assays and indirect
      immunofluorescence serotests for Chagas' disease. For these reasons they may
      better represent the universe of chagasic patients than would a sample of highly
      reactive sera obtained from chagasic patients in a single area endemic for T.
      cruzi. All acute and congenital cases showed positivity in the IgM and IgG TESA
      blots, while chronic cases were 100% positive for IgG antibodies. In nonchagasic
      sera, including 30 cases of visceral and muco-cutaneous leishmaniasis, the
      specificity index was 1.000, and no cross-reactions were observed. The TESA blot
      thus seems to be useful as a sensitive and specific diagnostic assay in cases of
      suspected acute or congenital T. cruzi infection and as a general confirmatory
      test for conventional Chagas' disease serology.

PMID- 8862575
TI  - Subtyping Listeria monocytogenes isolates genetically related to the Swiss
      epidemic clone.
AB  - Macrorestriction analysis by pulsed-field gel electrophoresis was used to assess
      the diversity of strains within the epidemic-associated electrophoretic type 1
      (ET1) clone of Listeria monocytogenes. For this purpose, a total of 144 isolates
      from Switzerland shown by multilocus enzyme electrophoresis to belong to the ET1
      were examined. These isolates were subtyped by macrorestriction analysis using
      the enzymes ApaI and SmaI and field inversion gel electrophoresis. Among these
      144 isolates, 45 were isolated in human listeriosis cases of the postepidemic
      period of 1988 to 1993 and 44 were isolated in animal listeriosis cases of the
      same period. Forty-seven isolates were from the epidemic period of 1983 to 1987,
      and eight additional isolates were from cattle from two different farms. Twenty
      nine different subtypes could be identified among the 144 isolates tested. Five
      major subtypes were found more frequently than the others during the postepidemic
      period, both in humans and in animals. Two of these subtypes had been previously
      implicated in outbreaks of listeriosis, thus suggesting that particular pulsed
      field gel electrophoresis subtypes may be frequently associated with disease in
      humans and animals. Two of these frequent subtypes were also suspected to be
      related to small clusters of listeriosis cases during the postepidemic period.
      The results obtained by typing epidemiologically related isolates from different
      animals within the same farms and from different body sites of a given patient
      confirmed the potential of macrorestriction analysis for epidemiological studies
      restricted to short periods of time and to small number of isolates. The analysis
      of 47 isolates related to the Swiss listeriosis epidemic period of 1983 to 1987
      and the use of Southern blotting and hybridization experiments show that the
      interpretation of relatedness between isolates presenting slightly different
      macrorestriction patterns may be more complex than commonly accepted. In such
      cases, careful interpretation of the potential molecular mechanisms leading to
      the differences observed between patterns is necessary.

PMID- 8862576
TI  - Fluconazole disk diffusion procedure for determining susceptibility of Candida
      species.
AB  - A simple disk diffusion test was defined for quick determination of the
      susceptibility of Candida species to fluconazole. The standard macrotube dilution
      reference method, the fluconazole E test, and a 25-microgram fluconazole disk
      test were all performed with each of 250 Candida species selected to provide a
      broad range of fluconazole MICs. All three methods were in excellent agreement.
      On RPMI 1640-glucose agar, isolates with inhibition zone diameters of > or = 19
      mm were all susceptible (MIC, < or = 8.0 micrograms/ml) by the E test and 94%
      were susceptible by the macrotube method. Strains with smaller zones were either
      resistant, intermediate (dose-dependent susceptibility), or susceptible by the
      reference methods. The disk test did not adequately separate fully resistant
      strains from those with dose-dependent susceptibility: additional quantitative
      tests are needed for the few strains that are not unequivocally susceptible by
      the disk method.

PMID- 8862577
TI  - Heterogeneity in susceptibility to metronidazole among Helicobacter pylori
      isolates from patients with gastritis or peptic ulcer disease.
AB  - Combination therapies that include metronidazole (MTZ) are the most successful
      therapies used in eradicating Helicobacter pylori. In this study, the prevalence
      and the relevance of heterogeneity in susceptibility to MTZ among H. pylori
      populations of 156 patients were evaluated. The results of this study show that
      37 patients (24%) were infected with MTZ-resistant H. pylori (MIC > or = 8
      micrograms/ml). Furthermore, 33% (52 of 156) of the patients were found to be
      infected with H. pylori populations heterogeneous for their susceptibility to
      MTZ. The reassessment of the MICs of MTZ for these 52 H. pylori populations
      revealed MTZ resistance in 28 of them, increasing the number of MTZ-resistant H.
      pylori populations among the 156 patients to 65 (42%). Out of 20 isolates, 2
      (10%) heterogeneous in their susceptibility to MTZ also appeared to be
      heterogeneous at the genome level as determined by randomly amplified polymorphic
      DNA fingerprinting. In conclusion, the results show the limitations and risk of
      possible misinterpretations when only a single colony, picked from the primary H.
      pylori populations isolated from patients, is analyzed for its susceptibility to
      MTZ.

PMID- 8862578
TI  - Epidemiological study of an outbreak due to multidrug-resistant Enterobacter
      aerogenes in a medical intensive care unit.
AB  - In 1993, 63 isolates of Enterobacter aerogenes were collected from 41 patients in
      a medical intensive care unit (ICU). During the same period, only 46 isolates
      from 32 patients were collected in the rest of the hospital. All isolates were
      analyzed by antibiotic resistance phenotype, and 77 representative isolates were
      differentiated by plasmid restriction analysis, ribotyping, and arbitrarily
      primed (AP)-PCR. The extended-spectrum beta-lactamases produced by 22 strains
      were characterized by determination of their isoelectric points and by
      hybridization of plasmid DNA with specific probes. The isolates were divided into
      25 antibiotic resistance phenotypes, either susceptible (group I) or resistant
      (group II) to aminoglycosides, and exhibited three phenotypes of resistance to
      beta-lactams: chromosomally derepressed cephalosporinase alone or associated with
      either extended-spectrum beta-lactamases (mainly of the SHV-4 type) or imipenem
      resistance. The results of the tests divided the 77 representative isolates
      (group I, n = 21; group II, n = 56) into 15 plasmid profiles, 14 ribotypes, and
      15 AP-PCR patterns. Although the resistant isolates (group II) exhibited
      different plasmid profiles, ribotyping and AP-PCR analysis demonstrated an
      identical chromosomal pattern, indicating an epidemiological relatedness. They
      were mainly found in the medical ICU and occasionally in other units. The
      susceptible strains (group I) had various and distinct markers and were mainly
      isolated in units other than the medical ICU. In conclusion, the presence of a
      nosocomial outbreak in an ICU and the spread of a multidrug-resistant epidemic
      strain throughout the hospital was confirmed. Ribotyping and AP-PCR represent
      discriminatory tools for the investigation of nosocomial outbreaks caused by E.
      aerogenes.

PMID- 8862579
TI  - A 16S rRNA-based PCR assay for detection and identification of granulocytic
      Ehrlichia species in dogs, horses, and cattle.
AB  - A PCR-based assay was developed for detecting DNA of granulocytic ehrlichiae in
      blood samples from dogs, horses, and cattle, Primers were designed from 16S rRNA
      sequence information to specifically amplify DNA from a newly identified Swedish
      Ehrlichia species. The 16S rRNA nucleotide sequence of this Swedish species
      differs in only two and three positions from the sequences of Ehrlichia
      phagocytophila and Ehrlichia equi, respectively, which were also amplified by
      this PCR system. For evaluation, PCR results were compared with microscopic
      examination of stained blood smears for the detection of granulocytes containing
      ehrlichiae (morulae). Thirty-four of 36 microscopically positive samples were
      also positive by PCR, and 6 microscopically negative samples were negative by PCR
      as well. Six samples, in which morulae-like structures had been seen, were
      negative by PCR, also at a lower annealing temperature and when a reamplification
      of the first PCR products was performed. The identities of the PCR products from
      some canine and equine isolates were verified by direct DNA sequencing and were
      found to be identical with the Ehrlichia sequence found in these animal species
      that had been obtained earlier. The sequences of a segment of approximately 600
      nucleotides from two bovine isolates were identical to that of E. phagocytophila,
      whereas the sequence of another bovine isolate differed in two positions from
      that of E. phagocytophila and in three positions from the sequences of the canine
      and equine isolates. Serum samples were analyzed by indirect fluorescent-antibody
      testing. Seventy-three percent of the animals which were positive by microscopy
      and PCR also had positive antibody titers. However, it was not possible to rely
      on a single serological result for diagnosis of present infection. It was,
      therefore, concluded that PCR was the most reliable method, useful in the
      clinical laboratory for specific and early diagnosis of granulocytic ehrlichiosis
      in animals.

PMID- 8862580
TI  - Diagnosis of disseminated candidiasis by measurement of urine D-arabinitol/L
      arabinitol ratio.
AB  - Relative amounts of D-arabinitol (fungal origin) and L-arabinitol (part of normal
      human metabolism) in urine were determined by gas chromatography and mass
      spectrometry from 61 hospitalized patients with hematological malignancies.
      Seventeen neutropenic patients with acute leukemia (with 53 samples) had
      disseminated yeast infections and received empiric antifungal therapy before
      confirmation of the diagnosis. Control groups consisted of 22 hematologic
      patients (76 samples) with either mucosal (n = 10) or urinary (n = 12) Candida
      colonization and 22 neutropenic patients (34 samples) with no clinical or
      laboratory signs of invasive yeast infection. Reference values were also obtained
      from 50 healthy adults (50 samples). The mean urine D-arabinitol/L-arabinitol
      ratio +/- standard deviation (range) was 16.91 +/- 41.79 (1.41 to 254.75) in
      patients with disseminated infection, 2.73 +/- 2.48 (1.11 to 19.00) in colonized
      hematologic patients, 2.12 +/- 0.84 (1.16 to 5.84) in neutropenic controls, and
      1.95 +/- 0.34 (0.97 to 3.44) in healthy adults (P < 0.001 between patients with
      disseminated infection and all control groups). The sensitivity and specificity
      of the assay for detecting disseminated yeast infection were, respectively, 88
      and 91% per patient (upper limit of normal, 4.00). Seventy-one percent of
      patients already expressed elevated values at the onset of empiric antifungal
      therapy. The diagnosis of disseminated infection was confirmed on average 21.7
      days after the first elevation of the D-arabinitol/L-arabinitol ratio. The method
      contributes to diagnosis of disseminated yeast infection and helps in monitoring
      patients at risk, to support the initiation of antifungal therapy at an early
      stage of the disease.

PMID- 8862581
TI  - Clinical importance of increased sensitivity of BacT/Alert FAN aerobic and
      anaerobic blood culture bottles.
AB  - Two recent multicenter blood culture studies found that BacT/Alert FAN (FAN)
      bottles (Organon Teknika, Durham, N.C.) had increased yields in detecting
      bacteremia and fungemia compared with standard BacT/Alert (STD) bottles. Because
      the clinical importance of this increase in microbial recovery is unknown, we
      performed a retrospective analysis to determine the frequency with which FAN
      bottles were the sole means of detecting an episode of bacteremia. There were
      1,047 positive blood cultures in which both study bottles were adequately filled
      and the organism isolated was judged to be the cause of sepsis: 240 (23%) were
      positive only in FAN bottles and 73 (7%) were positive only in STD bottles. Of a
      total of 664 episodes of bacteremia, 126 (19%) were identified only by FAN
      bottles and 43 (7%) were identified only by STD bottles (P < 0.0001). Episodes
      detected only by FAN bottles more often were recurrent events (23 of 126, or 18%)
      than episodes detected only by STD bottles (2 of 43, or 5%) (P < 0.05) and more
      commonly occurred in patients receiving theoretically effective antibiotic
      therapy (33 of 126 [26%] versus 4 of 43 [9%]) (P < 0.05). The medical records for
      patients with 127 of these episodes (92 FAN bottles only; 35 STD bottles only)
      were available for review. More than half of both FAN bottle-only (60 of 92, or
      65%) and STD bottle-only (20 of 35, or 57%) episodes were judged to be clinically
      important. We conclude that FAN bottles improve the detection of bacteremia and
      that the majority of the additional episodes detected are clinically important.
      The benefits of the greater yield in specific patient populations must be
      balanced against the higher costs of FAN bottles.

PMID- 8862582
TI  - Synergistic role of gaseous ammonia in etiology of Pasteurella multocida-induced
      atrophic rhinitis in swine.
AB  - One-week-old Large White piglets were weaned and allocated to 14 experimental
      groups, each composed of five animals. Each group was housed in a separate
      Rochester exposure chamber and exposed continuously to gaseous ammonia at either
      0, 5, 10, 15, 25, 35, or 50 ppm (two groups per exposure level). One week after
      ammonia exposure commenced, the pigs from one group at each exposure level were
      inoculated intranasally with 9 x 10(7) CFU of Pasteurella multocida type D. After
      a further 4 weeks of exposure, all the pigs were euthanized and the extent of
      turbinate degeneration was assessed by using a morphometric index (J.T. Done, D.
      H. Upcott, D. C. Frewin, and C. N. Hebert, Vet. Rec. 114:33-35, 1984) and a
      subjective scoring system (Ministry of Agriculture, Fisheries and Food, Atrophic
      Rhinitis: a System of Snout Grading, 1978). Exposure to ammonia at a
      concentration of 5 ppm or greater resulted in a significant increase in the
      severity of turbinate atrophy induced by P. multocida compared with that
      occurring in pigs kept in 0 ppm of ammonia. This effect was maximal at 10 ppm but
      decreased progressively at concentrations above 25 ppm. Regression analysis
      revealed a significant relationship between the severity of turbinate
      degeneration and the number of P. multocida organisms isolated from the nasal
      epithelium at the end of the experiment (R2 = 0.86). These findings suggest that
      exposure to ammonia facilitates the growth and/or survival of P. multocida within
      the upper respiratory tract of the pig, thereby contributing to the severity of
      the clinical disease atrophic rhinitis. Furthermore, exposure of pigs to ammonia
      at 10 ppm or greater, in the absence of either P. multocida or Bordetella
      bronchiseptica, induced a mild but statistically significant degree of turbinate
      atrophy. The findings of this study demonstrate that exposure to ammonia, at
      concentrations within the range encountered commonly in commercial piggeries,
      contributes to the severity of clinical lesions associated with atrophic
      rhinitis.

PMID- 8862583
TI  - Detection of hepatitis C virus by PCR in second-generation enzyme immunoassay
      seropositive blood donors by using matched pairs of fresh frozen plasma and pilot
      tube sera.
AB  - Between April 1993 and March 1995, 429 of 334,454 (0.13%) blood donations at the
      Toronto Centre of the Canadian Red Cross were reactive for hepatitis C virus
      (HCV) by second-generation enzyme immunoassay (EIA-2). Of the 429 EIA-2-positive
      donations, 189 (44%), 138 (32%), and 102 (24%) were positive, indeterminate, and
      negative by Second-Generation Recombinant Immunoblot Assay (RIBA-2). To assess
      HCV viremia and minimize the risk that specimen handling affected PCR-based
      detection, the qualitative AMPLICOR HCV test was performed on both pilot tube
      sera (PTS) and the corresponding fresh frozen plasma (FFP) from 294 EIA-2
      reactive donations. AMPLICOR PCR results for PTS and FFP were 100% concordant and
      were confirmed by nested HCV PCR for 27 of 294 donations. The AMPLICOR HCV test
      was positive for 127 of 140 (91%) of RIBA-2-positive donations (81, 91, and 96%
      of donations with two, three, and four reactive bands, respectively), 5 of 88
      (5.7%) indeterminate donations, and 0 of 66 (0%) RIBA-2-negative donations. The
      Third-Generation Recombinant Immunoblot Assay (RIBA-3) was performed on RIBA-2
      negative, -indeterminate, and -positive, PCR-negative donations. RIBA-3
      demonstrated enhanced specificity and resolved 18 of 88 (20%) of RIBA-2
      indeterminate samples as HCV antibody positive. The study demonstrates that PTS
      are as suitable as FFP for PCR-based detection of HCV and can be used to
      determine if EIA-2-reactive blood donors are viremic at the time of donation.

PMID- 8862584
TI  - Typing of Helicobacter pylori with monoclonal antibodies against Lewis antigens
      in lipopolysaccharide.
AB  - Recently, it has been shown that the lipopolysaccharide (LPS) O antigen of
      Helicobacter pylori contains Lewis x (Lex), Lewis y (Ley), or both Lex and Ley
      antigens. We applied a serotyping method for H. pylori by an enzyme-linked
      immunosorbent assay with monoclonal antibodies (MAbs) specific for these antigens
      and the related fucosylated H type 1 (H1) antigen. The selected MAbs recognized
      the Lex and/or Ley structures in the LPS of H. pylori. The agreement between the
      results of biochemical compositional analysis and the serological data validated
      our serotyping system. A total of 152 strains from different geographic origins
      (The Netherlands, Canada, Poland, Italy, and People's Republic of China) were
      examined for typeability based on the presence of Lewis antigens. One hundred
      twenty-nine (84.9%) strains were typeable, and 12 different serotyping patterns
      were observed; 80.9% of the strains contained Lex and/or Le(y) antigens, and
      18.4% reacted with the MAb against the related H1 antigen either alone or in
      combination with the Lex and/or Ley antigen. Our results show that the Lex and
      Ley antigens are frequently encountered in the LPS of H. pylori strains from
      various geographic origins. This typing method is an easy-to-perform technique,
      which can be used for strain differentiation in epidemiological studies of H.
      pylori infections.

PMID- 8862585
TI  - Identification and molecular characterization of serological group C streptococci
      isolated from diseased pigs and monkeys in Indonesia.
AB  - The present study was designed to comparatively investigate 34 beta-hemolytic
      streptococci isolated from infected pigs and monkeys from various islands in
      Indonesia. According to the serological and biochemical data, all 34 isolates
      were Lancefield's serological group C streptococci and could be identified as
      Streptococcus equi subsp. zooepidemicus. Of the 34 group C streptococci
      investigated, 28 grew on solid media in large, mucoid colonies, in fluid media at
      a uniform turbidity, and in soft agar in diffuse colonies. A decapsulation test
      with a hyaluronidase-producing Staphylococcus aureus strain revealed the
      hyaluronic acid nature of the capsular material. The remaining six streptococci
      grew on solid media in small, nonmucoid colonies, in fluid media as sediment with
      clear supernatant, and in soft agar in compact colonies. Determination of surface
      hydrophobicity by salt aggregation revealed a hydrophilic surface for the
      encapsulated bacteria and a hydrophobic surface for the unencapsulated group C
      streptococci. To further analyze the epidemiological relationships, all 34 mucoid
      and nonmucoid isolates from pigs and monkeys were subjected to protein and DNA
      fingerprinting. The latter was performed by pulsed-field gel electrophoresis. The
      protein profiles of all 34 isolates and the DNA profiles of 32 isolates appeared
      to be identical, with the DNA profiles of 2 isolates being closely related,
      indicating that a single virulent clone is responsible for this disease outbreak
      in Indonesia.

PMID- 8862586
TI  - Techniques for investigation of an apparent outbreak of infections with Candida
      glabrata.
AB  - A cluster of Candida glabrata isolates recovered from seven patients in an
      intensive care unit over a 10-week period were compared with a collection of
      isolates from six epidemiologically distinct outpatients and a reference strain
      by several DNA typing methods. Restriction enzyme analysis with HinII
      distinguished 13 strains from the 14 sources and was the method of choice. Pulsed
      field gel electrophoresis and random amplification of polymorphic DNA both
      detected nine types from the 14 sources; however, the results of these two
      methods did not always correlate. These methods demonstrated that five of the
      seven patients had distinguishable strains and that cross-infection was unlikely.

PMID- 8862587
TI  - Rubella reimmunization: comparative analysis of the immunoglobulin G response to
      rubella virus vaccine in previously seronegative and seropositive individuals.
AB  - Rubella virus (RV)-specific immunoglobulin G (IgG) antibodies were studied in
      military recruits undergoing unselected immunization with live attenuated
      measles, mumps, and rubella virus (MMR) vaccine. Three different whole-RV enzyme
      immunoassays (EIAs) and an epitope-specific EIA with a synthetic peptide (BCH
      178c) representing a heutralization domain on the RV E1 envelope protein were
      used. Before vaccination, 84.2, 87.7, and 84.5% of the subjects tested (n = 399)
      were found to be seropositive (> 10 IU/ml or assay equivalent) by the three whole
      RV EIAs, respectively, while only 82.5% were seropositive by the BCH-178c EIA.
      Although prevaccination seropositivity rates were similar for the whole-RV EIAs
      (sensitivity, 94 to 100%), many sera considered seropositive by the whole-RV EIAs
      had E1 peptide EIA antibody levels of < 10 IU/ml (sensitivity, 77.4 to 80.7%).
      One month after vaccination, 97.8, 97.2, and 93.5% of the subjects who were
      followed (n = 356) were seropositive by the three whole-RV EIAs, respectively,
      while 89% had BCH-178c peptide-specific IgG titers of > 10 IU/ml. After
      vaccination, depending on the assay used, up to 20.6% of initially seropositive
      individuals exhibited a greater than fourfold increase in RV-specific IgG, while
      up to 47.3% showed a greater than twofold increase. Increased antibody titers
      after vaccination (seroboosting) were most frequently associated with low levels
      of BCH-178c peptide-specific IgG before vaccination. RV protein-specific IgG was
      also studied by immunoblot assays in a subset (n = 56) of individuals receiving
      the MMR vaccine. Of these, 89.4 and 91.1% exhibited RV protein (E1, E2, and C
      protein)-specific IgG before and after vaccination, respectively. Seroboosting
      (two- to fourfold increase in EIA titers of individuals seropositive by the whole
      RV EIA before vaccination) was usually accompanied by a shift in the IgG
      immunoblot pattern from a single (E1) to multiple (E1-E1, E1-C, or E1-E2-C)
      specificities, suggesting exposure of new epitopes as a result of viral
      replication.

PMID- 8862588
TI  - Genotyping of Mycobacterium tuberculosis with additional markers enhances
      accuracy in epidemiological studies.
AB  - Two highly polymorphic Mycobacterium tuberculosis genomic domains, characterized
      by hybridization to the oligonucleotide (GTG)5, were identified as potential DNA
      fingerprinting probes. These domains were cloned [pMTB484(1) and pMTB484(2K4),
      respectively] and shown to be useful for genotype analysis by Southern blotting.
      These probes were used to genotype geographically linked strains of M.
      tuberculosis previously shown to have identical IS6110 fingerprints. Subsequent
      DNA fingerprints generated with MTB484(1) and MTB484(2K4) showed a high degree of
      polymorphism, allowing subclassification of IS6110-defined clusters into
      composites of smaller clusters and unique strains. Correlation of the molecular
      data with patient interviews and clinical records confirmed the sensitivity of
      these probes, as contacts were established only within subclusters. These
      findings demonstrate the requirement for multiple probes to accurately classify
      M. tuberculosis strains, even those with high copy numbers of IS6110. The
      enhanced accuracy of strain typing should, in turn, further our understanding of
      the epidemiology of tuberculosis.

PMID- 8862589
TI  - Antibody against an Anaplasma marginale MSP5 epitope common to tick and
      erythrocyte stages identifies persistently infected cattle.
AB  - A protein epitope of major surface protein 5 (MSP5), defined by monoclonal
      antibody (MAb) ANAF16C1, is conserved among Anaplasma species (E. S. Visser, T.
      C. McGuire, G. H. Palmer, W. C. Davis, V. Shkap, E. Pipano, and D. P. Knowles,
      Jr., Infect. Immun. 60:5139-5144, 1992) and is expressed in the salivary glands
      of infected ticks. A competitive inhibition ELISA (cELISA) for the detection of
      bovine anti-MSP5 antibodies was developed by using purified recombinant MSP5
      fusion protein and MAb ANAF16C1. The specificity of the recombinant-MSP5 cELISA
      within North America was established by using 261 serum samples from cattle in
      the regions of Hawaii and Northern Ontario where anaplasmosis is not endemic and
      from cattle proven by splenectomy or subinoculation of whole blood into
      susceptible splenectomized recipients to be uninfected. The maximum percent
      inhibition by these sera was 18%. Sera known to be positive were obtained from 35
      cattle either experimentally inoculated with infected erythrocytes or exposed to
      infected Dermacentor andersoni ticks. Thirty-four of the 35 serum samples
      inhibited MAb ANAF16C1 binding by > or = 25%. During acute infection, the MSP5
      cELISA detected antibodies prior to or concomitantly with the appearance of
      rickettsiae in erythrocytes. Antibodies were detectable in sera from persistently
      infected cattle inoculated as long as 6 years previously.

PMID- 8862590
TI  - Molecular typing of Yersinia pseudotuberculosis by using an IS200-like element.
AB  - The IS200-like insertion sequence (IS) is a 708-bp element recently found in
      Yersinia pestis. Its nucleotide sequence is 85% identical to that of IS200
      recovered in most Salmonella enterica isolates. It is also present in multiple
      copies in Y. pseudotuberculosis. In contrast, this IS is found in some (biotype
      1B strains) but not other Y. enterocolitica strains and is absent in the
      nonpathogenic yersiniae: Y. frederiksenii, Y. kristensenii, Y. intermedia, Y.
      bercovieri, and Y. mollaretii. The number and locations of the ISs in the Y.
      pseudotuberculosis genome vary among strains, resulting in a high degree of
      polymorphism, but IS fingerprints are stable after multiple subcultures of
      clinical isolates. The discriminative power of IS typing is better than that of
      ribotyping and almost as good as that of the time-consuming method of
      pulsotyping. Overall, IS200-like is a useful molecular marker in determining the
      epidemiology of Y. pseudotuberculosis infections.

PMID- 8862591
TI  - Comparison of mycobacteria growth indicator tube with BACTEC 460 for detection
      and recovery of mycobacteria from clinical specimens.
AB  - We compared the Mycobacteria Growth Indicator Tube (MGIT) system with the BACTEC
      460 (B460) and Lowenstein Jensen (LJ) systems for the recovery of mycobacteria
      (acid-fast bacteria [AFB]) from 1,441 clinical specimens. Excluding 13 isolates
      of Mycobacterium gordonae, 178 significant AFB isolates were recovered from 113
      patients. Isolates (119) of the Mycobacterium avium complex (MAC) accounted for
      67% of all isolates, while isolates (30) of the Mycobacterium tuberculosis
      complex (MTB) accounted for 17% of isolates. The MGIT system recovered 98 (82%)
      MAC and 27 (90%) MTB isolates, while the B460 system recovered 101 (85%) MAC and
      28 (93%) MTB isolates and the LJ system recovered 91 (76%) MAC and 25 (83%) MTB
      isolates. Overall, the MGIT system recovered 152 isolates of AFB (85.4%
      sensitivity), and the B460 and LJ systems recovered 151 (84.8% sensitivity) and
      137 (76.9% sensitivity) AFB isolates, respectively. The recoveries of AFB with
      combinations of media were as follows: MGIT + LJ, 93.2%; B460 + LJ, 92.1%; and
      MGIT + B460, 96.6%. Although the sensitivity of MGIT was equivalent to that of
      B460, MGIT required a longer incubation (median, 11 days) than did B460 (median,
      8 days) to become positive (P < 0.05).

PMID- 8862592
TI  - Identification of Mycobacterium avium complex in sarcoidosis.
AB  - Cell wall-defective bacteria which later reverted to acid-fast bacilli have been
      isolated from sarcoid tissue. These have not been conclusively shown to be
      mycobacteria. Specific PCR assays were applied to identify mycobacterial nucleic
      acids in these cultured isolates and in fresh specimens obtained from patients
      with sarcoidosis. Positive amplification and hybridization were observed with
      Mycobacterium avium complex- and/or Mycobacterium paratuberculosis-specific
      probes in five of the six cultured isolates and two fresh skin biopsy samples and
      one cerebrospinal fluid specimen. There was no amplification or hybridization
      with Mycobacterium tuberculosis or M. avium subsp. silvaticum probes,
      respectively. Patients' sera were also tested for antibody reactivities by
      immunoblotting with M. paratuberculosis recombinant clones expressing the 36,000
      molecular-weight antigen (36K antigen) (p36) and the 65K heat shock protein
      (PTB65K). All seven sarcoidosis, four of six tuberculosis, and all six leprosy
      patient serum specimens showed strong reactivity with p36 antigen. In contrast,
      13 of 38 controls showed only weak reactivity with p36 (P = 0.002 for controls
      versus sarcoidosis samples). Similarly, PTB65K reacted with high intensity with
      sera from 5 of 5 sarcoidosis, 5 of 6 tuberculosis, and 5 of 6 leprosy patients,
      compared with its low-intensity reaction with 5 of 22 controls (P = 0.001 for
      controls versus sarcoidosis samples). This study demonstrates the isolation
      and/or identification of M. paratuberculosis or a closely related M. avium
      complex strain from sarcoid skin lesions and cerebrospinal fluid. Furthermore,
      the reactivity of antibodies in sarcoid patient sera against p36 and PTB65K
      antigens was comparable to the reactivity of sera obtained from patients with
      known mycobacterial disease. Collectively, these data provide further support for
      the theory of the mycobacterial etiology of sarcoidosis.

PMID- 8862593
TI  - Frequency, intensity, species, and strains of oral Candida vary as a function of
      host age.
AB  - While the age of the host has been suggested as a determining factor in yeast
      carriage, no studies in which the genetic relatedness of isolates has been
      assessed in combination with the frequency and intensity of carriage as a
      function of host age have been performed in a single geographical locale and over
      a short time window. Therefore, by using a simple plating protocol to determine
      the frequency and intensity of carriage, sugar assimilation patterns to determine
      species, and Southern blot hybridization with the DNA fingerprinting probe Ca3
      combined with computer-assisted analysis to determine the genetic relatedness of
      strains of Candida albicans, yeast carriage was analyzed as a function of age.
      All test individuals lived in the Iowa City, Iowa, locale and, except for some of
      the 0.5- to 1.5-year-olds, were dentate. The results demonstrate that for this
      test population, the frequency, average intensity, predominant species, and
      genetic relatedness of C. albicans strains varied as a function of host age. In
      addition, comparison with oral commensal organisms from the Ann Arbor, Mich.,
      locale confirms the geographical specificity of C. albicans strains and the
      existence of an Iowa City-enriched strain which is most prevalent in elderly
      individuals.

PMID- 8862594
TI  - Rapid detection of point mutations of the Neisseria gonorrhoeae gyrA gene
      associated with decreased susceptibilities to quinolones.
AB  - Mutations in the gyrA gene resulting in amino acid changes at Ser-91 and Asp-95
      are significantly associated with decreased susceptibilities to quinolones in
      Neisseria gonorrhoeae. To detect these mutations, we developed a rapid and simple
      assay based on amplification of the region of the gyrA gene containing the
      mutation sites by PCR and digestion of the PCR product with a restriction enzyme.
      A naturally occurring HinfI restriction site was present in the region containing
      the Ser-91 codon, and an artificial HinfI restriction site was created in the
      region containing the Asp-95 codon by the method of primer-specified restriction
      site modification. The mutations generating alterations at Ser-91 and Asp-95 were
      detected as restriction fragment length polymorphisms of the PCR products
      digested with HinfI. Fifty-five clinical strains of N. gonorrhoeae were examined
      for mutations in the gyrA gene by this method. Mutations at Ser-91 and/or Asp-95
      were detected in all the 31 strains in which the mutations had been confirmed by
      DNA sequencing. Our method allows simultaneous testing of a large number of
      strains and provides results within 8 h. This rapid and simple assay could be a
      useful screening device for genetic alterations associated with decreased
      susceptibilities to quinolones in N. gonorrhoeae and could facilitate
      epidemiological studies on clinical isolates of N. gonorrhoeae with decreased
      susceptibilities to quinolones.

PMID- 8862595
TI  - Second-generation line probe assay for hepatitis C virus genotyping.
AB  - Because of the enormous variability of hepatitis C virus (HCV), the development
      of reliable genotyping assays is a formidable challenge. The optimal genotyping
      region appears to be the 5' untranslated region (UR) because of high conservation
      within, but considerable variability between, genotypes. In this study, 21 probes
      dispersed over seven variable 5' UR areas were applied to a line probe assay
      (LiPA) and used to analyze 506 HCV-infected sera from different geographical
      regions representing a multitude of subtypes. At least 31 different reactivity
      patterns emerged, with 404 (80%) of 506 distributed over 11 prototype patterns,
      in general corresponding to subtypes 1a, 1b, 2a/2c, 2b, 3a, 5a, and 6a and
      several type 4 subtypes. Subtyping specificity ranged from 97% in Hong Kong to
      90% in Europe but was only 11% in West Africa, while typing specificity was
      always 100% when samples from Vietnam were excluded. In a second evaluation, the
      subtype prediction by LiPA of 448 GenBank 5' UR HCV sequences was scored. Of the
      58 theoretically predicted patterns, 321 sequences (72%) were covered by the 11
      prototype patterns. We concluded that (i) the selected probes detected the
      corresponding signature motifs in the seven variable regions with 100%
      reliability; (ii) these motifs allowed correct type interpretation of samples
      collected worldwide, with the exclusion of Vietnam, Thailand, or Vietnamese
      patients residing in European hospitals; and (iii) subtyping specificities vary
      according to geographical region, with 11 prototype subtyping patterns
      identifying the majority of samples from Europe and the Americas. These results
      indicate that the LiPA is a reliable assay applicable to routine typing and
      subtyping of HCV specimens.

PMID- 8862596
TI  - Comparison of five tests for identification of Staphylococcus aureus from
      clinical samples.
AB  - Five different laboratory tests for the identification of Staphylococcus aureus
      were compared. Analyses of 271 presumptive S. aureus strains, supplemented with
      59 well-defined methicillin-resistant S. aureus (MRSA) isolates, were performed.
      Only the Staphaurex Plus (Murex Diagnostics, Dartford, United Kingdom) and the
      Pastorex Staphplus (Sanofi, Marnes-La-Coquette, France) tests displayed 100%
      sensitivity. The observed difference with the free-coagulase test (Bacto
      coagulase plasma; Difco, Detroit, Mich.), a bound-coagulase (clumping factor)
      test, and the former Staphaurex test (Murex Diagnostics) was caused mainly by the
      inability of these three tests to identify some MRSA strains correctly. Among
      Polish MRSA isolates included in the analysis, a group of free-coagulase-negative
      S. aureus strains was detected. Genetic typing by random amplification of
      polymorphic DNA revealed that the strains showing aberrant behavior when the
      different test results were compared belonged to limited number of S. aureus
      clones.

PMID- 8862597
TI  - Serological cross-reactions between Bartonella quintana, Bartonella henselae, and
      Coxiella burnetii.
AB  - The clinical manifestations of Q fever and bartonelloses can be confused,
      especially in cases of infectious endocarditis. Differential diagnosis of the
      diseases is important because the treatments required for Q fever and
      bartonelloses are different. Laboratory confirmation of a suspected case of
      either Q fever or bartonelloses is most commonly made by antibody estimation with
      an indirect immunofluorescence assay. With an indirect immunofluorescence assay,
      258 serum samples from patients with Q fever were tested against Bartonella
      henselae and Bartonella quintana antigens, and 77 serum samples from patients
      with infection by Bartonella sp. were tested against Coxiella burnetii antigen.
      Cross-reactivity was observed: more than 50% of the chronic Q fever patients
      tested had antibodies which reacted against B. henselae antigen to a significant
      level. This cross-reaction was confirmed by a cross-adsorption study and protein
      immunoblotting. However, because the levels of specific antibody titers in cases
      of Bartonella endocarditis are typically extremely high, low-level cross-reaction
      between C. burnetii antibodies and B. henselae antigen in cases of Q fever
      endocarditis should not lead to misdiagnosis, provided serology testing for both
      agents is performed.

PMID- 8862598
TI  - Diagnosis of extrapulmonary tuberculosis by Gen-Probe amplified Mycobacterium
      tuberculosis direct test.
AB  - A total of 294 specimens collected from nonrespiratory sites of 268 patients were
      tested for direct detection of Mycobacterium tuberculosis complex by the Gen
      Probe Amplified Mycobacterium tuberculosis Direct Test (AMTD). The specimens
      included ascitic, pleural, pericardial, and synovial fluids, abscess aspirates,
      and tissue and lymph node biopsy samples, as well as gastric aspirates and
      cerebrospinal fluid samples. All samples were processed by the N-acetyl-L
      cysteine-sodium hydroxide decontamination procedure prior to testing. Twenty
      samples showed acid-fast bacilli on auramine staining, and 48 samples were
      positive by AMTD, 9 of which were negative for M. tuberculosis complex by
      culture. After reviewing the patients clinical charts to resolve discrepancies,
      the test result of one cerebrospinal fluid sample was considered to be false
      positive by AMTD. The overall sensitivity, specificity, positive predictive
      value, and negative predictive value were 83.9, 99.6, 97.9, and 96.3%,
      respectively. No significant differences were found when AMTD results obtained
      with specimens of nonrespiratory origin were compared with assay results obtained
      with samples of respiratory origin (P > 0.05). In conclusion, our results
      demonstrate that AMTD performs equally well with all types of specimens.

PMID- 8862599
TI  - In vivo detection of porcine reproductive and respiratory syndrome virus RNA by
      in situ hybridization at different times postinfection.
AB  - We studied the distribution of porcine reproductive and respiratory syndrome
      virus (PRRSV) RNA in tissues by in situ hybridization at different times
      postinfection (p.i.). The probe used for in situ hybridization was prepared by
      reverse transcription of PRRSV RNA, followed by PCR amplification of the cDNA.
      The sequence amplified corresponded to 433 bp from PRRSV open reading frame 7,
      which is contained in the nucleocapsid protein gene and which is highly conserved
      in both European and American strains (H. Mardassi, L. Wilson, S. Mounir, and S.
      Dea, J. Clin. Microbiol. 32:2197-2203, 1994). An immunohistochemical technique
      was used to detect PRRSV antigen in tissue from virus-infected animals by using a
      monoclonal antibody specific for the PRRSV nucleocapsid protein (E.A. Nelson, J.
      Christopher-Hennings, T. Drew, G. Wensvoort, J.E. Collins, and D.A. Benfield, J.
      Clin. Microbiol. 31:3184-3189, 1993). The detection of PRRSV RNA was conducted in
      tissues of 6-week-old pigs that had been infected with one of three different
      field PRRSV isolates and collected at times ranging from 4 to 42 days p.i.
      Hybridization signals specific for PRRSV RNA were detected in lung, lymphoid
      tissues, alveolar macrophages (obtained by lavage at the time of necropsy),
      Peyer's patches, and kidney. The PRRSV-positive cells in these tissues appeared
      to be predominantly macrophages. In lung tissue we also obtained evidence
      suggesting the involvement of type II pneumocytes in the replication of PRRSV.
      During the acute period of infection there was a close correlation between the
      detection of RNA and the detection of nucleocapsid protein in individual cells.
      At later times p.i. (28 and 42 days p.i.), instead, more cells containing only
      PRRSV RNA than those containing PRRSV RNA and also expressing PRRSV nucleocapsid
      protein were detected. These results suggest that PRRSV RNA might persist in the
      tissues of infected animals for a longer time than PRRSV antigen expression.

PMID- 8862600
TI  - Sequence variation in the 18S rRNA gene, a target for PCR-based malaria
      diagnosis, in Plasmodium ovale from southern Vietnam.
AB  - Field surveys of malaria were performed in southern Vietnam by using an acridine
      orange staining method for rapid diagnosis and a PCR-based, microtiter plate
      hybridization method for accurate diagnosis. A total of three patients of
      Plasmodium ovale infection were detected, but PCR-amplified DNA of the P. ovale
      isolates from two of the patients did not hybridize with the P. ovale-specific
      probe. Analysis of the target sequence in the 18S rRNA gene indicated that in the
      DNA of isolates from both patients three nucleotides in the probe region from the
      typical P. ovale sequence were different, with deletions of two nucleotides and
      the substitution of one nucleotide. These results may suggest that in addition to
      molecular biological methods, careful microscopic examination of stained thin
      blood films is still required in studies of the prevalence of different malaria
      species.

PMID- 8862601
TI  - Modified India ink preparation for Cryptococcus neoformans in cerebrospinal fluid
      specimens.
AB  - A novel modified India ink technique for the diagnosis of Cryptococcus neoformans
      in cerebrospinal fluid specimens is described. It employs 2% chromium mercury and
      India ink. This technique allows a clear identification of some external and
      internal structures of the organism. Three layers from the outer capsule that
      have previously been discerned only by electron microscopy are distinguished.

PMID- 8862602
TI  - Factors influencing Cryptosporidium testing in Connecticut.
AB  - To describe patterns of testing for Cryptosporidium oocysts in stool samples,
      Connecticut laboratories were surveyed. Different detection methods were used.
      Most laboratories examined stools specifically for Cryptosporidium only on
      physician request. The rate of positive tests varted widely (0 to 28%). Higher
      rates of positivity were associated with the use of monoclonal antibody methods,
      the use of two or more staining procedures, and testing of stool specimens in
      addition to those requested by physicians.

PMID- 8862603
TI  - Epidemiological differentiation of pathogenic strains of Salmonella enteritidis
      by ribotyping.
AB  - The usefulness of two-way ribotyping, performed with SphI and PstI, as a genetic
      marker for a series of pathogenic Salmonella enteritidis strains is reported.
      Eighteen combined ribotypes were differentiated, a discrimination index of 0.77
      was reached, a genetic relationship dendrogram was traced, and the results were
      applied in an epidemiological study.

PMID- 8862604
TI  - Accelerated infectivity of tick-transmitted Lyme disease spirochetes to vector
      ticks.
AB  - We determined whether the span of infectivity of Lyme disease spirochetes
      (Borrelia burgdorferi) to vector ticks varies with the mode of infection in
      laboratory mice. Noninfected larval deer ticks were permitted to feed on two
      strains of spirochete-infected mice that had been naturally (via tick bite) and
      parenterally (via needle injection) infected with B. burgdorferi 2, 4, or 8 weeks
      earlier, and engorged ticks were dissected and examined for spirochetes by direct
      immunofluorescence microscopy. After initial infection, spirochetal infectivity
      to ticks was less efficient in needle-infected mice than in mice infected via
      tick bites. Tick-transmitted spirochetes develop more rapidly from the skin of
      infected mice and do not induce a strong antispirochete antibody response during
      the early stage of infection.

PMID- 8862605
TI  - Screening protocol for Torulopsis (Candida) glabrata.
AB  - A screening test has been developed for the presumptive identification of
      Torulopsis (Candida) glabrata from other common clinical isolates of yeast-like
      fungi. An interlaboratory comparison of a protocol consisting of morphology on
      cornmeal Tween 80 agar and trehalose fermentation at 42 degrees C was successful
      in differentiating T. glabrata from other taxa that are frequent or possible
      clinical isolates. The screening results for 517 clinical yeast isolates, 241 of
      which were T. glabrata, were compared with their final identification via
      commercial systems (API20C Yeast Identification System [bioMERIEUX, Hazelwood,
      Mo.] and Rapid Yeast Identification Panel [Dade Microscan, Sacramento, Calif.]).
      The trehalose screening test has a sensitivity and a specificity of 97.8 and
      95.8%, respectively, and a positive predictive value of 97.4% and a negative
      predictive value of 96.5%. Overall, the trehalose screen had an efficiency rating
      of 93.9% for ruling in or out T. glabrata. Since T. glabrata represents a
      substantial part of the workload in a clinical laboratory, a significant
      reduction in direct and indirect costs should be realized.

PMID- 8862607
TI  - Evaluation of a novel PCR-based diagnostic assay for detection of Mycobacterium
      tuberculosis in sputum samples.
AB  - We report on a PCR-based assay we have developed for the detection of
      Mycobacterium tuberculosis in sputum samples. One hundred sputum specimens, which
      included 34 culture-positive and 66 culture-negative specimens, were evaluated
      with this system. Of the 34 culture-positive specimens, 31 were PCR positive, and
      60 of the culture-negative specimens were PCR negative. An internal standard has
      been included in the assay system to monitor PCR inhibition and to confirm the
      reliability of the PCR assay.

PMID- 8862606
TI  - Isolation of Campylobacter concisus from feces of children with and without
      diarrhea.
AB  - A prospective study compared fecal isolation rates of Campylobacter concisus for
      children with diarrhea and without diarrhea by a filter technique in which media
      were incubated for 4 days in a microaerobic atmosphere. No statistically
      significant difference in isolation rates was found (13.2% in patients with
      diarrhea and 9% in controls). Moreover, 35 of 37 children attending the same day
      care center harbored different C. concisus strains, as was demonstrated by
      arbitrary primer PCR DNA fingerprinting. These data suggest a lack of a
      pathogenic role for C. concisus in enteritis.

PMID- 8862608
TI  - The mtp40 gene is not present in all strains of Mycobacterium tuberculosis.
AB  - A multiple PCR-based assay that targets IS6110 and the mtp40 gene was evaluated
      for the rapid differentiation of Mycobacterium bovis and M. tuberculosis, two of
      the causative agents of tuberculosis. The IS6110 target is present in both
      species, whereas the mtp40 gene was thought to be specific for M.tuberculosis (P.
      Del Portillo, L.A. Murillo, and M.E. Patarroyo, J. Clin. Microbiol. 29:2163-2168,
      1991). However, the mtp-40 gene is not present in all M. tuberculosis strains
      and, hence, is not useful for differentiating M.tuberculosis and M.bovis.

PMID- 8862609
TI  - Evaluation of an infectivity standard for real-time quality control of human
      immunodeficiency virus type 1 quantitative micrococulture assays. Participating
      Laboratories of The AIDS Clinical Trials Group.
AB  - Quantitative microculture assays of cryopreserved human immunodeficiency virus
      type 1-infected cell suspensions and culture supernatants were compared among
      seven assays sites. There was no significant change in titer during 1 year of
      storage. The overall standard deviation for infected cell suspensions was
      approximately 0.8 log10 virus titer. A method for detecting deviant assay results
      was developed and was used to identify two donor cell preparations (n = 54) that
      gave consistently low titers.

PMID- 8862610
TI  - Isolation of an unusual mycobacterium from an AIDS patient.
AB  - A mycobacterium isolated from a clinical sample of an AIDS patient was identified
      as Mycobacterium interjectum by direct 16S rRNA sequence determination. High
      performance liquid chromatography, however, revealed a mycolic acid pattern which
      was different from the one shared by the previously analyzed strains of this
      species.

PMID- 8862611
TI  - Detection of human herpesvirus 6 and human herpesvirus 7 in the submandibular
      gland, parotid gland, and lip salivary gland by PCR.
AB  - In order to define the major sites of persistence of human herpesvirus 6 (HHV-6)
      and HHV-7, PCR with DNAs from more than 100 specimens of 3 different salivary
      glands was performed. HHV-6 DNA was detected in 52 (88.1%) of 59 submandibular
      gland, 17 (63.0%) of 27 parotid gland, and 9 (52.9%) of 17 lip salivary gland
      specimens. On the other hand, HHV-7 DNA was detected in 59 (100%) of 59
      submandibular gland, 23 (85.2%) of 27 parotid gland, and 10 (58.8%) of 17 lip
      salivary gland specimens. These findings demonstrate that salivary glands are a
      site of persistent infection of both HHV-6 and HHV-7 and that among the three
      types of salivary gland examined, the submandibular gland is the primary one in
      which these herpesviruses, especially HHV-7, persist.

PMID- 8862612
TI  - CDC group IIc: phenotypic characteristics, fatty acid composition, and isoprenoid
      quinone content.
AB  - Twenty strains of glucose-utilizing, small gram-negative slightly pleomorphic
      rods that grew well aerobically and that were isolated from clinical specimens
      formed a phenotypically similar group that was designated CDC group IIc. The
      phenotypic characteristics of CDC group IIc were most similar to those of CDC
      groups IIe and IIh, the major differences being that CDC group IIc produced acid
      from sucrose, hydrolyzed esculin, and usually reduced nitrate. The CDC group IIc
      strains were analyzed by gas-liquid chromatography for their cellular fatty acid
      compositions, and all contained relatively large amounts of isobranched hydroxy
      and nonhydroxy acids. High-performance liquid chromatography and mass
      spectrometry analysis of the quinone extract showed menaquinone-6 as the major
      component. Both the cellular fatty acid and isoprenoid quinone compositions were
      consistent with the profiles of CDC groups IIe and IIh. Thirty percent of the
      isolates were from human blood.

PMID- 8862613
TI  - Analysis of clinical and environment Yersinia isolates in the Republic of
      Georgia.
AB  - The Center for Infectious Diseases Control, Georgian Ministry of Health, isolated
      2,493 Yersinia enterocolitica and Y. enterocolitica-like strains, 22 Y. pestis
      strains, and 21 Y. pseudotuberculosis strains from 130,574 clinical and
      environmental samples. Analysis of 100 Y. enterocolitica and Y. enterocolitica
      like strains showed none to be within traditional pathogenic biogroups or
      serogroups, and none carried genetic markers for virulence. However, some strains
      were enterotoxigenic in infant mice, while others were associated with prolonged
      carriage in adult mice.

PMID- 8862614
TI  - Pulmonary paracoccidioidomycosis misdiagnosed as Pneumocystis pneumonia in an
      immunocompromised host.
AB  - Yeast cells of Paracoccidioides brasiliensis can resemble the cysts of
      Pneumocystis carinii in smears stained with Grocott's modification of the Gomori
      methanamine silver stain. Furthermore, P. brasiliensis can cross-react in
      material stained with a widely used P. carinii immunofluorescent stain which uses
      monoclonal antibodies. The need to differentiate P. brasiliensis and P. carinii
      will become more important as the increasing incidence of immunosuppression
      results in the reactivation of latent P. brasiliensis infections.

PMID- 8862615
TI  - Multiplex PCR provides a low-cost alternative to DNA probe methods for rapid
      identification of Mycobacterium avium and Mycobacterium intracellulare.
AB  - A multiplex PCR designed to differentiate Mycobacterium tuberculosis complex
      organisms from M. avium and M. intracellulare was used to test 105 isolates
      identified by DNA probe methods as M. avium, M. intracellulare, or M. avium
      complex type X. The multiple PCR correctly identified 33 of 34 isolates
      identified by commercial probe methods as M. avium and all 51 isolates identified
      as M. intracellulare. The 20 isolates identified as M. avium complex type X by
      probe were identified as Mycobacterium spp. by the multiplex method. These
      results confirm that the multiplex PCR, which is simple to perform and cheaper
      than commercial probe methods, is suitable for routine identification of M. avium
      and M. intracellulare.

PMID- 8862616
TI  - Detection of Legionella pneumophila serogroup 1 antigen in nonconcentrated urine
      and urine concentrated by selective ultrafiltration.
AB  - We evaluated a commercially available radioimmunoassay technique for detecting
      the soluble antigen of Legionella pneumophila serogroup 1 using concentrated and
      nonconcentrated urine. Concentration was achieved by selective ultrafiltration.
      The sensitivity of the technique was 60.9% for nonconcentrated urine and 80.4%
      for concentrated samples, with 100% specificity in both cases.

PMID- 8862617
TI  - Fecal lactoferrin screening assay for inflammatory bacterial diarrhea.

PMID- 8862618
TI  - Reliability of immunoassays in diagnosis of neurocysticercosis.

PMID- 8862619
TI  - Molecular analysis of isolates of Salmonella typhi from patients with fatal or
      nonfatal typhoid fever or aberrant clinical presentations.

PMID- 8862620
TI  - A new Seckel-like syndrome of primordial dwarfism.
AB  - Seckel syndrome is a rare, recessively inherited disorder of severe growth
      retardation and distinct craniofacial, orodental, and skeletal anomalies. Even
      though there are well-established minimum diagnostic criteria for this syndrome,
      controversy exists about its boundaries and criteria for exclusion. We studied 2
      remarkably similar, unrelated children with most of the clinical and radiographic
      manifestations of Seckel's original patient. Although their craniofacial and
      orodental anomalies are typical of Seckel syndrome, 1 child has unusual
      appearance of the hands and feet that have not been previously associated with
      it. This patient appears to define a new Seckel-like syndrome and suggests
      heterogeneity in this type of primordial dwarfism.

PMID- 8862621
TI  - Early-infantile galactosialidosis: clinical, biochemical, and molecular
      observations in a new patient.
AB  - Few patients with the early-infantile form of galactosialidosis have been
      described to date. Presented here is the first Italian case. Fetal hydrops was
      detected by ultrasound at week 24 of gestation. At birth, the infant presented
      with hypotonia, massive edema, a flattened coarse facies, telangiectasias, and
      hepatosplenomegaly, but no dysostosis multiplex. The patient died 72 days
      postpartum. Excessive sialyloligosaccharides in urine, as well as vacuolation of
      lymphocytes and eosinophilic granulocytes in peripheral blood, were indicative of
      a lysosomal storage disease. In the patient's fibroblasts, both alpha
      neuraminidase and beta-galactosidase activities were severely reduced, and
      cathepsin A activity was < 1% of control levels, confirming the biochemical
      diagnosis of galactosialidosis. However, in contrast to previously reported early
      infantile cases, a normal amount of protective protein/cathepsin A mRNA was
      detected on Northern blots. This mutant transcript was translated into a
      precursor protein that was not processed into the mature enzyme and lacked both
      protective and catalytic activities.

PMID- 8862622
TI  - Prenatal monitoring in a family at high risk for ornithine transcarbamylase (OTC)
      deficiency: a new mutation of an A-to-C transversion in position +4 of intron 1
      of the OTC gene that is likely to abolish enzyme activity.
AB  - DNA analysis of a male propositus with ornithine transcarbamylase (OTC)
      deficiency documented an A-to-C substitution in position +4 of intron 1. No other
      abnormalities were observed in the OTC gene, or at 563 bp upstream of the 5'
      site, which included a promoter region, or at 383 bp downstream of the
      termination codon, which included a polyadenylation signal sequence. This
      mutation produces an RsaI site in the sequence, which was used for prenatal
      monitoring in the fourth and fifth pregnancies. DNA from amniotic cells in the
      former case were positive for RsaI digestion and the SRY gene (sex determinant
      region Y), indicating hemizygosity for the mutant allele. OTC activity was not
      measurable, and mRNA of the OTC gene was not detected by Northern blotting in the
      affected fetal liver. RT-PCR (reverse transcription-PCR) demonstrated only the
      wild-type allele. Thus, the mutation interferes with RNA processing, and an
      extremely low amount of normally spliced mRNA for the OTC gene seems to have
      caused the disease in our patient. The fetus of the fifth pregnancy was a normal
      male, as confirmed postnatally.

PMID- 8862623
TI  - Holoprosencephaly: epidemiologic and clinical characteristics of a California
      population.
AB  - Holoprosencephaly is a brain defect resulting from incomplete cleavage of the
      embryonic forebrain. It involves forebrain and facial malformations that can
      range from mild to severe. The epidemiology of holoprosencephaly is largely
      unknown. Published prevalence estimates have been derived from clinic-based case
      series, and suggested risk factors for holoprosencephaly have been identified in
      case reports, without confirmation from systematically conducted population-based
      studies. Using data from a population-based birth defects registry in California,
      we describe the epidemiologic and clinical characteristics of cytogenetically and
      phenotypically distinct types of holoprosencephaly. A total of 121 cases was
      identified among a cohort of 1,035,386 live births and fetal deaths. The
      prevalence of holoprosencephaly was 1.2 per 10,000 births (95% confidence
      interval 1.0-1.4 per 10,000). Of all cases, 41% (50/121) had a chromosomal
      abnormality, most commonly Trisomy 13. Among the 71 cytogenetically apparently
      normal cases, 18 had recognizable syndromes and the remaining 53 were of unknown
      cause. Among the cytogenetically abnormal cases, females had a greater risk than
      males (odds ratio = 2.3,95% confidence interval [1.2, 4.4]). Among the
      cytogenetically normal cases, increased risks were observed among Hispanic whites
      (OR = 1.8 [0.9, 3.6]) and cases whose mother was born in Mexico (OR = 2.2 [1.0,
      4.5]). Approximately 46% of all cases had alobar holoprosencephaly, the most
      severe form of the forebrain malformation. The facial phenotype did not strongly
      predict the severity of the brain defect; however, severity was inversely
      correlated with length of survival. This study is the first to present findings
      based on such a large population-based series of infants/fetuses affected by
      holoprosencephaly, and demonstrates the importance of investigating the component
      subgroups of this rare phenotype.

PMID- 8862624
TI  - Molecular cytogenetic diagnosis of Williams syndrome.
AB  - Williams syndrome (WS) is characterized by distinct facial changes, growth
      deficiency, mental retardation, and congenital heart defect (particularly
      supravalvular aortic stenosis), associated at times with infantile hypercalcemia.
      Molecular genetic studies have indicated that hemizygosity at the elastin locus
      (7q11.23) causes WS. The purpose of this study was to confirm that this regional
      deletion, involving the elastin locus, is the cause of WS in Japan, and to
      clarify the correlation between the phenotype and the elastin locus. Thirty-two
      patients with WS and thirty of their relatives were examined by fluorescent in
      situ hybridization (FISH), using the WS chromosome region (WSCR) probe. All
      patients had cardiovascular disease (100%), 30 had typical WS facial changes
      (94%), 31 had mental retardation or developmental delay (97%), 16 were small-for
      date at birth (50%), 14 had short stature (44%), and 13 had dental anomalies
      (41%). No relatives showed any manifestation of WS. Hemizygosity for a region of
      7q11.23, involving the elastin locus, was found in all WS patients, but was not
      found in the 30 relatives.

PMID- 8862625
TI  - Prenatally diagnosed de novo apparently balanced complex chromosome
      rearrangements: two new cases and review of the literature.
AB  - Complex chromosome rearrangements (CCR) are rare structural rearrangements.
      Currently six cases of prenatally diagnosed balanced de novo CCR have been
      described. We present two new cases of prenatally ascertained balanced de novo
      CCR. In the first case, an amniocentesis revealed a balanced de novo three-way
      CCR involving chromosomes 5, 6, and 11 with a pericentric inversion of chromosome
      5 [four breaks]. In the second case, a balanced de novo rearrangement was
      identified by amniocentesis which involved a reciprocal translocation between
      chromosomes 3 and 8 and a CCR involving chromosomes 6, 7, and 18 [six breaks].
      The use of whole chromosome painting helped elucidate the nature of these
      rearrangements. A review of the postnatally ascertained cases suggests that most
      patients have congenital anomalies, minor anomalies, and/or developmental
      delay/mental retardation. In addition, there appears to be a relationship between
      the number of chromosome breaks and the extent of phenotypic effects. The paucity
      of information regarding prenatally diagnosed CCR and the bias of ascertainment
      of postnatal CCR cases poses a problem in counseling families.

PMID- 8862626
TI  - Congenital vocal cord paralysis with possible autosomal recessive inheritance:
      case report and review of the literature.
AB  - We describe an infant with congenital vocal cord paralysis born to consanguineous
      parents. While autosomal dominant and X-linked inheritance have been previously
      reported in this condition, we conclude that the degree of parental consanguinity
      in this case strongly suggests autosomal recessive inheritance. Although we
      cannot exclude X-linked inheritance, evidence from animal studies demonstrates
      autosomal recessive inheritance and provides a possible molecular basis for
      congenital vocal cord paralysis.

PMID- 8862627
TI  - Aneuploidy detection in human sperm nuclei using PRINS technique.
AB  - Rapid and specific identification of chromosomes can be attained in situ using
      the PRimed IN Situ (PRINS) labelling technique. We have adapted this technique to
      mature human sperm in combination with a protocol for simultaneous decondensation
      and denaturation of sperm nuclei. This strategy allowed us to obtain double
      labelling of human spermatozoa in a < 2-hr reaction. In the present study, we
      report the estimates of disomy for chromosomes 3, 7, 10, 11, and 17 on 64,642
      spermatozoa from 2 normal males. The incidences of disomy ranged from 0.28-0.34%.
      There were no significant interindividual or interchromosomal differences in
      disomy rates.

PMID- 8862628
TI  - Chondrodysplasia punctata, humero-metacarpal type: a second case.
AB  - We report on a boy with symmetrical rhizomelic shortness of the upper limbs and
      punctate epiphyseal calcifications noted at birth. Radiographs documented short
      and wide humeri, symmetrical brachymetacarpy, coronal clefts of the veretebrae,
      and punctate calcifications in the spine, sacrum, shoulder, feet, and trachea.
      Borochowitz [1991] described a similar patient with an apparently new syndrome of
      chondrodysplasia punctata (CP), distinct from previously described forms. He
      suggested the term "chondrodysplasia punctata, humero-metacarpal (HM)" type. We
      present our patient as a second case of this form of CP.

PMID- 8862629
TI  - Skeletal and cardiac malformations with thrombocytopenia: a new syndrome?
AB  - We describe a female patient with multiple anomalies suggestive of a new
      syndrome. Manifestations include: VSD and ASD, mild developmental delay,
      conductive hearing loss, minor facial anomalies, thrombocytopenia, and
      radiological findings (including carpal fusion). Some of these manifestations may
      be present in the Keutel syndrome, IVIC syndrome, and the 10qter deletion
      syndrome. However, none of these syndromes can explain the spectrum of anomalies
      seen in our patient.

PMID- 8862630
TI  - Deletion of chromosome 21 in a girl with congenital hypothyroidism and mild
      mental retardation.
AB  - We report on a girl with a large interstitial deletion of the long arm of
      chromosome 21 and with mild mental retardation, congenital hypothyroidism, and
      hyperopia. The deletion [del(21)(q11.1-q22.1)] extends molecularly from marker
      D21S215 to D21S213. The distal breakpoint is not clearly defined but is situated
      between markers D21S213 and IFNAR. This patient has the largest deletion of
      chromosome 21 known without having severe mental retardation or malformations.
      The deletion does not involve the "Down syndrome chromosome" region, the region
      of chromosome 21 which in trisomy causes most of the manifestations of Down
      syndrome. Apparently, the proximal part of the long arm of chromosome 21 does not
      include genes that are responsible for severe clinical effects in the event of
      either deletion or duplication, since several reported patients with either
      trisomy or deletion of this region have mild phenotypic abnormalities. Congenital
      hypothyroidism is much more common in Down syndrome than in the average
      population. Thus, the congenital hypothyroidism of the present patient might
      indicate that there is one or several genes on the proximal part of chromosome
      21, which might be of importance for the thyroid function.

PMID- 8862631
TI  - Syndrome of lipoatrophic diabetes, vitamin D resistant rickets, and persistent
      Mullerian ducts in a Turkish boy born to consanguineous parents.
AB  - Congenital lipodystrophy (MIM 269700), persistent Mullerian ducts (MIM 261550),
      and vitamin D resistant rickets (MIM 277440) were observed in an 8 1/2-year-old
      boy born to consanguineous parents. Measurements of hormone sensitive lipase
      activity from a sample of the suprapubic fat depot were normal. Although the
      insulin receptor appeared normal (including autophosphorylation), insulin action,
      assessed by induction of total mRNA, was decreased. The vitamin D receptor was
      normal in size and amount, with a slight decrease in affinity for 1,25(OH)2D3.
      Induction of 24-hydroxylase, used as a measure of responsiveness to 1,25(OH)2D3,
      was only mildly defective. Assessment of anti-Mullerian hormone (AMH) failed to
      show any abnormalities explaining the persistent Mullerian ducts. We speculate
      that a defect in general hormone action common to 1,25(OH)2D3, insulin, and AMH
      may exist in this patient although we can not exclude the unlikely possibility
      that he is homozygous for two or three individually rare mutations.

PMID- 8862632
TI  - COACH syndrome: report of two brothers with congenital hepatic fibrosis,
      cerebellar vermis hypoplasia, oligophrenia, ataxia, and mental retardation.
AB  - Congenital hepatic fibrosis (CHF) is probably the most common cause of non
      icteric hepatosplenomegaly and is encountered mainly in children and young
      adults. We describe here two brothers from healthy, non-consanguineous parents.
      The patients showed early hepatosplenomegaly, portal hypertension, and no
      apparent kidney involvement. Clinical and laboratory findings were similar in
      both patients. Liver biopsies showed the presence of broad septa of fibrous
      tissue containing abundant bile ducts, portal tracts enlarged by fibrosis, and
      preserved lobular architecture. The histological findings were suggestive of CHF.
      Ophthalmological assessment demonstrated visual impairment with mild exotropia,
      nystagmus, and oculomotor apraxia. Neurological examination showed moderate
      mental retardation and cerebellar ataxia. Brain MRI confirmed cerebellar
      malformation with inferior vermis hypoplasia. This pattern of defects is
      consistent with COACH syndrome (Cerebellar vermis hypoplasia, Oligophrenia,
      congenital Ataxia, Coloboma, Hepatic fibrocirrhosis) which has previously been
      reported in five other cases. Our report may contribute to a better delineation
      of the COACH syndrome phenotype in the spectrum of oculo-encephalohepato-renal
      disorders.

PMID- 8862633
TI  - Previously apparently undescribed syndrome: shallow orbits, ptosis, coloboma,
      trigonocephaly, gyral malformations, and mental and growth retardation.

PMID- 8862634
TI  - Is the autosomal dominant Optiz GBBB syndrome part of the
      DiGeorge/velocardiofacial syndrome with deletions of chromosome area 22q11.2?

PMID- 8862635
TI  - Autosomal dominant "Opitz" GBBB syndrome due to a 22q11.2 deletion.

PMID- 8862636
TI  - Horace Wells (1815-1848).

PMID- 8862637
TI  - Continuous renal replacement therapy in critically ill patients: monitoring
      circuit function.
AB  - There is currently no universally accepted method to monitor circuit function or
      guidelines for circuit replacement during continuous renal replacement therapies
      (CRRT). The objectives of this study were to diagnose the causes of circuit
      failure, identify factors responsible for circuit clotting and determine a
      predictive monitor of circuit function. The CRRT technique used in this study was
      continuous venovenous haemodialysis (CVVHD). Continuous monitoring of circuit
      pressures (pre- and post-haemofilter and their difference: the transfilter
      pressure gradient) was used to diagnose the causes of circuit failure. In
      circuits ceasing due to clotting, the factors thought to contribute,
      anticoagulation, haematocrit and platelet count, were measured at the
      commencement of CVVHD and every eight hours thereafter until circuit failure.
      Monitors of circuit function, creatinine clearance and plasma to diafiltrate urea
      ratio were measured every eight hours and compared to the transfilter pressure
      gradient. During a three-month period data was collected on five consecutive
      patients (41 consecutive haemofilters). Clotting of the haemofilter (63%) and air
      detection chamber (7.5%) were the most common identifiable causes of circuit
      failure. The duration of their circuit life was described using multiple
      regression analysis, i.e. hours of filter life = -82.8 + (delta platelet count x
      0.25) + (delta haematocrit x 3.6) + (circuit flow [ml/min] x 4) R2 = 0.77. A rise
      in transfilter pressure gradient and a fall in haemofilter function discriminated
      clotted filters with falling function (decrease in creatinine clearance and urea
      ratio) from unclotted filters. In any circuit an increase of 26 mmHg or more in
      the transfilter pressure gradient accurately predicted circuit failure due to
      clotting and imminent cessation of function. Increases in platelet count,
      haematocrit, and low circuit flows are important determinants of haemofilter
      life. The measurement of transfilter pressure gradient across the haemofilter is
      an accurate bedside monitor of circuit function.

PMID- 8862638
TI  - The influence of surgery on cytokines in patients with intra-abdominal sepsis.
AB  - The cytokine cascade which is triggered by severe sepsis may contribute to
      progressive organ dysfunction and death from sepsis. This cascade may be
      accentuated by surgery for sepsis and pre-treatment with cytokine blockers could
      possibly ameliorate the response. This prospective controlled study determined
      the effect of surgery in 11 haemodynamically stable patients undergoing
      laparotomy for intra-abdominal sepsis. Serum levels of endotoxin, IL-1, IL-6, IL
      8 and TNF-alpha were determined; blood cultures, features of systemic
      inflammatory response, and organ dysfunction were monitored over the peri
      operative period. There was considerable variation in the serum cytokine levels.
      The preoperative IL-6 levels were significantly elevated in the septic patients
      and a threefold increase in IL-6 levels occurred in both groups postoperatively.
      An increase in TNF-alpha did not achieve significance because of high levels in
      control patients with cancer. Cytokine release which occurs during abdominal
      surgery is increased in patients with intra-abdominal sepsis.

PMID- 8862639
TI  - Haemodynamic and renal effects of dopexamine after cardiac surgery in children.
AB  - Dopexamine hydrochloride, a synthetic dopamine analog with predominantly beta and
      delta agonist properties, has been shown to improve cardiac performance and renal
      function in adults with heart failure. This study was designed to investigate the
      haemodynamic and renal effects of dopexamine in children after cardiac surgery.
      Seven children were selected in whom a need for postoperative vasodilation after
      cardiac surgery was anticipated. Haemodynamics and renal function were determined
      under baseline conditions and during a continuous infusion of dopexamine at 2 and
      6 micrograms.kg-1.min-1 for 90 minutes, the sequence being randomized for the
      initial dose. Cardiac output was measured by thermodilution and glomerular
      filtration rate (GFR) and renal plasma flow (RPF) by the clearances of inulin and
      para-aminohippurate respectively. Dopexamine induced a dose-related increase in
      cardiac index (CI) expressed as mean (SD) from 3.5 (0.7) to 3.9 (0.76) and 4.5
      (0.8) l.min.-1m-2 (both P < 0.05), and in heart rate (HR) from 107 (17) to 122
      (17) and 136 (17) beats.min-1 (P < 0.05). Stroke volume index (SVI) and mean
      systemic pressure were unchanged, but pulmonary wedge pressure decreased from 14
      (3) to 11 (4) and 12 (3) mmHg (both P < 0.05). Systemic vascular resistances
      (SVR) decreased from 24 (7) to 20 (5) mmHg.l-1.min-1.m-2 (P < 0.05), with
      dopexamine 6 micrograms.kg-1.min-1. Renal blood flow (RBF) increased from 319
      (113) to 441 (230) and 410 (138) ml.min-1.m-2 (both P < 0.05), GFR from 115 (32)
      to 142 (34) and 146 (29) ml.min-1.1.73m-2 (both P < 0.05), urine output and
      fractional excretion of sodium respectively from 3.12 (2) to 7.16 (8) and 7.21
      (6) ml.kg-1 (both P < 0.05) and from 2.24 (1) to 4.25 (3.4) (P < 0.05) and 3.15
      (3.1)% (n.s.). The fraction of CI delivered to the kidneys, the fraction of RBF
      filtered in the kidneys, plasma renin activity and aldosterone levels remained
      unchanged. In children after cardiac surgery, dopexamine increases CI at the
      expense of a concomitant increase in heart rate and demonstrates few selective
      vascular systemic or intrinsic renal actions.

PMID- 8862640
TI  - An outbreak of hepatitis A in an intensive care unit.
AB  - We describe an outbreak of hepatitis A that occurred in an Intensive Care Unit
      (ICU) in a regional hospital in North Queensland. Seven people were infected
      including two patients, two close contacts of the index patient and three ICU
      nursing staff. The index case was admitted with an overdose and multiple trauma;
      he was not suspected to be incubating hepatitis A. The outbreak was initiated as
      a result of inadequate precautions taken whilst handling the index patient's
      bile. Problems identified upon reviewing the outbreak were inadequate terminal
      cleaning of equipment, food consumption in the ICU and inadequate handwashing
      practices. Implementation and maintenance of standard infection control practices
      is vital if further outbreaks of hospital-acquired hepatitis A and other enteric
      infections are to be avoided. We also suggest that the inactivated hepatitis A
      vaccine be considered for ICU staff.

PMID- 8862641
TI  - Brain and blood concentrations of propofol after rapid intravenous injection in
      sheep, and their relationships to cerebral effects.
AB  - The time-course of propofol concentrations in the blood and brain following rapid
      administration of three doses were examined using a sheep preparation and
      regional pharmacokinetic techniques. These were compared to the time-course of
      cerebral effects of propofol reported previously. There were marked differences
      between the time-course of propofol concentrations in arterial blood and the
      brain, with a close relationship between the time-course of brain concentrations
      and effects on depth of anaesthesia and CBF. There was evidence that the effect
      of propofol on cerebral blood flow altered its own rate of elution from the
      brain. Hysteresis between arterial propofol concentrations and cerebral effects
      following rapid i.v. administration therefore appears to have a pharmacokinetic
      basis, and conventional compartmental pharmacokinetic analysis using blood
      concentrations alone may fail to accurately predict the time-course of both brain
      propofol concentrations and depth of anaesthesia.

PMID- 8862642
TI  - Axillary brachial plexus block in two hundred consecutive patients.
AB  - Two hundred consecutive, minimally-sedated patients presenting for upper limb
      surgery were audited prospectively to determine the overall clinical success
      rate, extent of cutaneous neural blockade, reliability and complication rate of
      each indicator of axillary sheath entry, and degree of patient satisfaction. The
      axillary sheath was identified, using a 22 gauge, short-bevelled needle, by one
      of four indicators, whichever was elicited first (paraesthesia, arterial or
      venous puncture, or tethering by the axillary sheath). Alkalinized mepivacaine
      1.2%, 50 ml then was injected. The cutaneous distribution of the block was mapped
      in the presence of minimal sedation. Anaesthesia was supplemented with peripheral
      nerve blocks where necessary. Patients were followed up with a mailed
      questionnaire and surgeon interview. The overall clinical success rate was 92.5%,
      improving to 99% with supplementary nerve blocks. Complete anaesthesia distal to
      the elbow was achieved in 85% of patients. Complications were common, but
      generally mild and transient: mild acute local anaesthetic toxicity, 3.5%;
      axillary tenderness and bruising, 12%; and dysaesthesias, 12.5%. Despite this,
      patient satisfaction was high (97%).

PMID- 8862643
TI  - Anaesthesia for children with mucopolysaccharidoses.
AB  - The mucopolysaccharidoses are a group of inherited disorders of metabolism, with
      varying clinical manifestations. A number of them present anaesthetic
      difficulties. This paper presents a summary table of the syndromes and reviews
      our experience over ten years with patients with these diagnoses. The clinical
      presentations, anaesthetic management, and complications are described. The
      effect of age and diagnosis on airway difficulties was studied. There were 31
      patients, 28 of whom required anaesthesia, on a total of 99 occasions, for 115
      procedures. The patients with Hunter, Hurler and Maroteaux-Lamy syndromes had
      significantly more airway difficulties as they grew older, and compared with
      patients in this group with other syndromes. Patients with Hurler's syndrome may
      have coronary artery involvement and one patient was given fentanyl and
      pancuronium for this reason. He proved impossible to intubate and an emergency
      tracheostomy was performed.

PMID- 8862644
TI  - Audit of unbooked paediatric post-anaesthesia admissions to intensive care.
AB  - We performed an audit of booked and unbooked admissions to a paediatric intensive
      care unit (PICU) after anaesthesia over a 19 month period in order to determine
      whether unbooked admissions were predictable, or whether there were any
      preventable anaesthetic factors responsible for PICU admission, and to evaluate
      the necessity of PICU admission in all study patients. Data was collected from
      the PICU database and from the medical records, especially the anaesthesia
      records, of unbooked admissions. There were 640 admissions to the PICU from the
      operating theatres, with 35 (5%) unbooked. Of the unbooked admissions, 71% were
      considered predictable and 20% had preventable features. There was an appropriate
      use of intensive care resources by these unbooked patients, with 77% having PICU
      specific therapies (compared with 88% of booked cases). This quality assurance
      tool was relatively easy to perform, however it has numerous limitations
      hampering future routine use.

PMID- 8862645
TI  - Sensitivity and specificity of the Hemochron, Hemotec and APTT for the detection
      of low concentrations of heparin.
AB  - This study compared two bedside methods recommended for the detection of low
      concentrations of heparin and the activated partial thromboplastin time (APTT),
      with reference to a laboratory measure of heparin concentration. Patients
      undergoing cardiopulmonary bypass had blood drawn at four stages when low levels
      of heparin could be expected. At each stage four tests were performed: whole
      blood clotting time using a Hemochron analyser with a Saline-Rinsed test
      cartridge, whole blood clotting time using a Hemotec analyser with a High Range
      Heparinase test cartridge, APTT, and heparin concentration by polybrene
      neutralization. Thirty patients were studied. The sensitivity of the Saline
      Rinsed Hemochron, Hemotec High Range Heparinase, and APTT in detecting
      concentrations of heparin less than 1 U/ml was 38%, 40% and 97%, respectively,
      while specificities were 87%, 90%, and 30%, respectively. Neither the Saline
      Rinsed Hemochron, nor the Hemotec Heparinase cartridge reliably detected
      concentrations of heparin less than 1 U/ml.

PMID- 8862646
TI  - A survey of anaesthetic manpower and training in the south-west Pacific region.

PMID- 8862647
TI  - The taste of intravenous thiopentone.
AB  - Patients sometimes notice an onion or garlic taste before losing consciousness
      with thiopentone. An assessment of 113 patients revealed that 42% of patients
      noticed this taste. The effect was observed less in older patients. There was no
      statistically significant difference in the incidence between men and women.
      Premedicated patients had a lower incidence, but this was explained by the
      greater proportion of older patients receiving a premedication. If the taste
      effect of thiopentone is genetically determined then it is a different gene to
      thiocarbamate which has about 75% tasters.

PMID- 8862648
TI  - Anaphylaxis to mivacurium.

PMID- 8862649
TI  - Serum tryptase measurement in diagnosis of intraoperative anaphylaxis caused by
      hydatid cyst.

PMID- 8862650
TI  - Use of esmolol during intraoperative atrioventricular rhythm.

PMID- 8862651
TI  - Masseter spasm and elevated creatine kinase after intravenous induction in a
      child.

PMID- 8862652
TI  - Intracranial pressure monitoring in an Australian military hospital.

PMID- 8862653
TI  - Severe cerebral fat embolism.

PMID- 8862654
TI  - Flumazenil reverses paradoxical reaction to midazolam in a child.

PMID- 8862655
TI  - Transient radicular irritation as a complication of spinal anaesthesia with
      hyperbaric 5% lignocaine.

PMID- 8862656
TI  - An aid to placing the laryngeal mask airway (LMA)

PMID- 8862657
TI  - Emergency ventilation in a child using the suction port of an Ayre's T-piece.

PMID- 8862658
TI  - InterLink and the Lever Lock cannula--potential flow reduction.

PMID- 8862659
TI  - The use of surrogate gases for anaesthetic monitor calibration.

PMID- 8862660
TI  - Hepatitis C and anaesthetic breathing systems.

PMID- 8862661
TI  - Using the Pall HME Filter as an oxygen therapy device in recovery room.

PMID- 8862662
TI  - Inhaled prostacyclin as a selective pulmonary vasodilator.

PMID- 8862663
TI  - Inhaled prostacyclin (PGI2) versus nitric oxide (NO)

PMID- 8862664
TI  - Datex AS3 monitor failure.

PMID- 8862665
TI  - "Awareness" during endoscopic procedures.

PMID- 8862666
TI  - Text processing by digital voice recognition.
AB  - OBJECTIVE: To evaluate digital voice recognition in free text mode. STUDY DESIGN:
      A standard medical text (182 words and punctuation marks) was dictated four times
      each by six people using a commercially available voice recognition system.
      RESULTS: The time used, including the time needed for making corrections,
      decreased from a median of 14.5 (6.3-18.8) minutes in the first session to a
      median of 6.7 (5.1-15.7) in the fourth session. the number of corrections
      necessary in the last session was a median of 20.5 (15-97)-i.e., 11% of the
      number of words in the text. All users described working with the system as
      highly strenuous. Dictating the same text with a dictaphone took median 1.4 (0.9
      1.6) minutes and about five minutes of typing and correction time. CONCLUSION:
      Although the total time was about the same with the two methods, the time for the
      pathologist increased fourfold when using the voice recognition system. To obtain
      acceptable input speed, an appropriate template module is essential.

PMID- 8862667
TI  - Reproducibility of Bayesian belief network assessment of breast fine needle
      aspirates.
AB  - OBJECTIVE: To assess the consistency of diagnosis of fine needle aspiration
      biopsies of breast lesions by three experienced and five less experienced
      pathologists using conventional means and applying a Bayesian belief network
      (BBN) to 10 diagnostic features to support diagnostic decision making. STUDY
      DESIGN: Forty fine needle aspiration biopsies, previously assessed by one of the
      experienced pathologists both conventionally and using a BBN, were assessed by
      two further experienced pathologists and five less experienced pathologists.
      RESULTS: Using the BBN, the experienced pathologists arrived at diagnoses in
      agreement with an established consensus at a slightly lower rate than by
      conventional means. The less experienced pathologists arrived at the correct
      diagnoses no more frequently with the help of the BBN than conventionally.
      CONCLUSION: As used in this study, the BBN did not help less experienced
      pathologists to interpret their observations but did not enable less experienced
      pathologists to identify how their observations differed and affected their
      diagnoses. The prototype system used in this study has since been upgraded by
      providing computer graphic displays of the features to be observed so that a more
      uniform mental image can be held by the participating pathologists. This will be
      tested with the same study design.

PMID- 8862668
TI  - Acetylcarnitine modulation of the morphology of rat hippocampal synapses.
AB  - OBJECTIVE: To measure the effect of chronic administration of acetylcarnitine
      (ALCAR) on the morphologic plasticity of rat hippocampal synapses. STUDY DESIGN:
      Computer-assisted morphometry was carried out on the ultrastructure of
      hippocampal synapses in 6-, 12- and 22-month-old rats and in age-matched animals
      chronically treated with ALCAR from the age of 1 month up to when they were
      killed. Synaptic numeric (Nv) and surface (Sv) densities as well as the synaptic
      average area (S) were measured in the dentate gyrus supragranular layer. RESULTS:
      In control animals, Nv was constant between 6 and 12 months of age but
      significantly decreased in 22-month-old rats, S did not show significant
      differences due to age and Sv was unchanged between 6 and 12 months but decreased
      significantly in the old animals. In ALCAR-treated rats, Nv increased and S
      decreased significantly vs. age-matched controls. Sv showed lifespan constancy
      among the age groups analyzed. In ALCAR-treated rats the number of synapses
      smaller than 0.08 microns 2 increased by 18%, 9% and 10% at 6, 12 and 22 months
      of age, respectively. CONCLUSION: We interpret these findings to represent
      positive modulation of the synaptic structural dynamics in ALCAR-treated animals
      through improvements in energy provision at nerve terminals.

PMID- 8862669
TI  - Total number of astrocytes in the molecular layer of the dentate gyrus of rats at
      different ages.
AB  - OBJECTIVE: To estimate the total number of glial fibrillary acidic protein (GFAP)
      positive astrocytes and the volume of GFAP-positive structures in the left
      molecular layer of the dentate gyrus by unbiased methods to provide reference
      values for neurotoxicologic model studies. STUDY DESIGN: The number of astrocytes
      was estimated by the optical fractionator, and the volume of GFAP-positive
      structures was estimated by the Cavalieri principle in male Wistar rats at 3, 13
      and 25 months of age. RESULTS: The number of astrocytes was statistically
      significantly increased in the oldest age group (111.000 +/- 11.000 [mean +/-
      SD]) as compared to the youngest group (88.000 +/- 15.000). The value for 13
      month-old rats was intermediate (103.000 +/- 14.000). The GFAP volume per
      astrocyte was statistically significantly reduced in the oldest age group (441 +/
      103 microns 3) as compared to the youngest one (673 +/- 146). The GFAP volume
      per astrocyte of 13-month-old rats was intermediate (629 +/- 245). CONCLUSION:
      There is a slight increase in the number of astrocytes with age and a slight
      decrease in GFAP volume per astrocyte with age. Stereology combined with
      immunohistochemistry is a strong tool for estimation of the total number of
      accurately identified cells in different brain regions.

PMID- 8862670
TI  - Application of attributed graphs in diagnostic pathology.
AB  - OBJECTIVE: To compute attributed graphs based upon calculation of the minimum
      spanning tree (MST) for various applications in diagnostic lung pathology. STUDY
      DESIGN: The study design included assistance in histologic diagnosis,
      confirmation of the diagnosis in single cases, measurement of texture alterations
      after induction chemotherapy, estimation of prognosis of operated-on lung cancer
      patients and analysis of lung cancer cells in association with differentiation
      markers. The histologic slides were Feulgen stained, and features of the
      integrated optical density (IOD) were associated with the nodes of the MST. The
      same procedure was applied to immunohistochemically and ligand histochemically
      stained slides by calculation of the mean staining intensity of the cytoplasm of
      tumor cells. A measure for structural entropy was introduced by computing the
      relative differences in distance and IOD between neighboring tumor cells in a
      1/r2 field of force. In addition, the current of entropy was computed. RESULTS:
      Structural entropy reflects alterations in regular textures; the current of
      entropy is an especially good prognostic parameter in lung cancer. In
      immunochemistry and ligand histochemistry, construction of the attributed MST
      permits detailed insight into locally different staining behavior of tumor cells
      and immunocompetent cells. CONCLUSION: Attributed graphs contain important
      information that can be used for the estimation of survival or for confirmation
      of diagnostic entities, such as tumor cell types.

PMID- 8862671
TI  - Flow cytometric analysis of bronchoalveolar lavage and venous blood lymphocyte
      phenotype for the diagnosis of acute graft rejection in lung transplant patients.
      The Lung Transplant Group, Ospedale Maggiore di Milano.
AB  - OBJECTIVE: To investigate modifications of phenotype in bronchoalveolar lavage
      (BAL) and venous blood lymphocytes as markers of acute organ rejection in lung
      transplant patients. STUDY DESIGN: Five consecutive patients receiving successful
      single lung transplants between March 1991 and April 1992 were followed for two
      years; serial bronchoscopies with BAL and transbronchial biopsies (TBBs) were
      performed. BAL and venous blood lymphocyte cytofluorimetry was performed at every
      procedure, and an index, (blood T4/T8)/(BAL T4/T8), was computed. RESULTS: The
      index was always > or = 3 in the two patients who did not have graft rejection
      and always < 3 in the two patients who had repeated episodes of acute rejection
      (even when no rejection was apparent). The index was frequently < 3 when
      cytomegalovirus infection was diagnosed. CONCLUSIONS: Since BAL is far less
      invasive and carries lower risks than TBB, the index might be considered, if our
      results are confirmed, for screening patients at high risk of acute rejection.
      TBB could be used as a confirmatory tool for patients who have an index < 3.

PMID- 8862672
TI  - Data-driven approaches to decision making in automated tumor grading. An example
      of astrocytoma grading.
AB  - OBJECTIVE: To compare four data-driven approaches to automated tumor grading
      based on morphometric data. Apart from the statistical procedure of linear
      discriminant analysis, three other approaches from the field of neural computing
      were evaluated. STUDY DESIGN: The numerical basis of this study was computed
      tomography-guided, stereotactically obtained astrocytoma biopsies from 86
      patients colored with a combination of Feulgen and immunhistochemical Ki-67
      (MIB1) staining. In these biopsies the cell nuclei in four consecutive fields of
      vision were evaluated morphometrically and the following parameters determined:
      relative nuclei area, secant lengths of the minimal spanning trees and relative
      volume-weighted mean nuclear volumes of the proliferating nuclei. RESULTS: Based
      on the analysis of these morphometric features, the multivariate-generated HOM
      grading system provides the highest correct grading rates (> 90%), whereas the
      two widely employed qualitative histologic grading systems for astrocytomas yield
      correct grading rates of about 60%. For automated tumor grading all approaches
      yield similar grading results; however, back-propagation networks provide
      reliable results only following an extensive training phase, which requires the
      use of a supercomputer. All other neurocomputing models can be run on simple UNIX
      workstations (AT&T, U.S.A). CONCLUSION: In contrast to discriminant analysis,
      backpropagation and Kohonen networks, the newly developed neural network
      architecture model of self-editing nearest neighbor nets (SEN3) provides
      incremental learning; i.e., the training phase does not need to be restarted each
      time when there is further information to learn. Trained SEN3 networks can be
      considered ready-to-use knowledge bases and are appropriate to integrating
      further morphometric data in a dynamic process that enhances the diagnostic power
      of such a network.

PMID- 8862673
TI  - Grading in superficial papillary bladder carcinoma, with an emphasis on nuclear
      orientation.
AB  - OBJECTIVE: To develop a computerized analysis method that could reflect not only
      cellular anaplasia but also the orientation (PV) of neoplastic elements and could
      allow the separation of low (grade G 1 and G 2a) and high (G 2b) grades of
      superficial papillary bladder tumors (SPBTs). STUDY DESIGN: Cellular anaplasia is
      based on classic morphometric parameters, such as mean and standard deviation of
      area, perimeter, roundness and aspect ratio (length/width ratio) of 50 papillary
      bladder tumors (16 G 1, 10 G 2a and 24 G 2b according to Pauwels). Orientation of
      the major axis of each nucleus with respect to the true basal membrane was
      calculated using the SD of valve distribution. RESULTS: No statistically
      significant differences were found between cases showing contiguous grades (G 1
      versus G 2a or G 2a versus G 2b). PV, SD of the area and SD of the perimeter were
      the parameters that could significantly distinguish between G 1 and G 2b and
      between G 1 plus G 2a and G 2b (P < .05). When comparing G 1 with G 2a plus G 2b,
      only PV and SD of the area were statistically significant. CONCLUSION:
      Quantification of the irregularities in the orientation of nuclei with respect to
      the basal membrane may improve morphometric classification of low grade SPBTs.

PMID- 8862674
TI  - A new flow cytometric approach to the analysis of DNA and a second parameter.
AB  - OBJECTIVE: To describe a new method of analyzing flow cytometry data by
      continuously variable gating (CVG), which is particularly useful for analysis of
      cellular DNA plus a second parameter, such as the proliferation marker Ki-67.
      STUDY DESIGN: CVG was compared with histogram subtraction (HS) using Overton's
      cumulative subtraction and with boxed gating (BG). Background suppression
      (thresholding) was used to remove outliers. The comparisons were carried out on a
      human bladder cancer cell line (T24) in various phases of cell proliferation and
      on disaggregated cells of fresh specimens of human prostatic and bladder
      carcinoma. With similar counts in control and test samples, data did not have to
      be normalized. RESULTS: In most cases histogram analysis by CVG was similar to
      that of BG and HS. However, when true positive values showed only a slight shift
      in fluorescence intensity, HS generated higher values than CVG. When true
      positive values exhibited strong fluorescence signals, HS could falsely include
      minor shifts in fluorescence values, and CVG became more accurate. CVG generated
      a continuous plot of percent positive events that could be superimposed on the
      DNA histogram, or a DNA histogram of positive events only could be created. This
      latter method demonstrated the DNA subpopulations containing most of the positive
      cells and improved discrimination of small subpopulations. CONCLUSION: The CVG
      method presents data in unique graphic form from flow cytometry assays of DNA and
      a second parameter. It is relatively objective and particularly useful in
      analyzing specimens with multiple DNA populations.

PMID- 8862675
TI  - Reproducibility of DNA ploidy and S-phase values from paraffin-embedded tissue.
AB  - OBJECTIVE: To determine the degree of variability of DNA flow cytometric results
      between two types of flow cytometers. STUDY DESIGN: Single-cell suspensions were
      made from 40 paraffin blocks of ovarian carcinoma using a modified Hedley
      procedure. These samples were consecutively analyzed in both Coulter's Profile II
      and Elite Flow cytometers. Gated and ungated data were collected and analyzed
      using Phoenix flow system's multicycle software. RESULTS: There were 16 (40%) DNA
      diploid, 23 (58%) DNA aneuploid and 1 DNA tetraploid tumor. The degree of
      variability in the DNA index coefficient of variation of the G0/G1 diploid peak,
      percentage of S phase, percentage of G2M, percentage of debris plus percentage of
      clumps were compared. Excellent correlations of the results were obtained in the
      DNA index (r = .999) and in percentage of S phase (r = .946). CONCLUSION: It is
      feasible to standardize variables of flow cytometric instruments to obtain
      reproducible results.

PMID- 8862676
TI  - Optimization of linear image combination for segmentation in red-green-blue
      images.
AB  - OBJECTIVE: To present an iterative algorithm that selects the optimal pair of
      grey level image components of red-green-blue (RGB) and hue-luminance-saturation
      (HLS) color image models and the optimal weighting factor for automated
      segmentation of the structure of interest in color images. STUDY DESIGN: The
      method was based on a stepwise technique, searching for the image combination
      that yielded the maximum two-sample t value for the grey levels of the object of
      interest and of the background. As a result, a transformed grey level image
      providing a two-peak grey level histogram suitable for automated thresholding was
      provided. RESULTS: The segmentation of collagen bundles in hematoxylin and eosin
      stained slides of cutaneous melanomas is presented as an example. Though each of
      the RGB and HLS grey level images showed extensive overlap of objects and
      background, the combined image facilitated clear-cut discrimination. CONCLUSION:
      The proposed algorithm permits the discrimination of specified objects in color
      images that are not characterized by grey level in any of the underlying grey
      level image components.

PMID- 8862677
TI  - DNA quantification as a prognostic factor in prostatic adenocarcinoma.
AB  - OBJECTIVE: To determine if DNA quantification on fine needle aspiration (FNA) has
      a predictive value in cancer of the prostate. STUDY DESIGN: Fifty-four patients
      with cancer of the prostate during the years 1979-1989 were selected; all were
      diagnosed by FNA. The smears were studied using image cytometry. RESULTS: With
      the type of histogram and value of entropy, two large groups with high and low
      degrees of malignancy were obtained. Survival was utilized as a variable of
      interest. Kaplan-Meier survival curves for both groups were formulated, and the
      results were supported with statistical data. CONCLUSION: The survival
      differences between both groups were statistically significant (P < .001), thus
      demonstrating the predictive value of DNA quantification.

PMID- 8862678
TI  - Transgenic models for arthritis: useful clues to be gained?
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of unknown
      aetiology. Much of our understanding regarding the pathogenesis of this disease
      has been derived from studies in rodents induced to develop arthritis with
      injected agents. More recently with the advent of transgenic mouse technology,
      animal models of arthritis have been generated either by design or by
      serendipity, and have provided insight into the role of cytokines in particular
      in contributing to the pathogenesis of arthritis. This short editorial summarizes
      recent advances in this field and how this has increased our understanding of RA.

PMID- 8862679
TI  - Metabolic bone disease of prematurity.
AB  - Metabolic bone disease is recognized with increasing frequency in very-low-birth
      weight infants. Radiological changes characteristic of rickets have been found in
      55% of infants with a birth weight of less than 1000 g and in 23% of infants
      weighing less than 1500 g at birth. Twenty-four per cent of infants with a birth
      weight of less than 1500 g have fractures. The main aetiological factor is
      insufficient phosphorus supplementation. The aetiology is, however,
      multifactorial and also includes calcium deficiency, vitamin D deficiency,
      certain drugs, aluminium loading and immobilisation. The method of choice in
      detecting subclinical mineral bone disease of prematurity is measurement of bone
      mineral density, but there is as yet no single good diagnostic method available
      for premature infants. The optimal mineral and vitamin D requirement of the
      premature infant must be established so that proper recommendations can be given.
      The current recommended vitamin D dose in Europe (ESPGAN 800-1000 IU/day) is
      probably too high when extra minerals are supplied. Moreover, the duration of
      mineral supplementation may need to be continued until the infant has reached a
      body weight of 3.5 kg. This article deals with the aetiology, pathogenesis,
      diagnosis and future prospects of metabolic bone disease of prematurity.

PMID- 8862680
TI  - Clinical significance of antinuclear antibodies in systemic rheumatic diseases.
AB  - Autoantibodies directed to intracellular antigens can be detected in many
      systemic rheumatic diseases. In this review, we discuss the clinical significance
      of antinuclear antibodies (ANA) associated with systemic lupus erythematosus
      (SLE), Slogren's syndrome, scleroderma and polymyositis/dermatomyositis, the
      immunogenetic factors associated with these four autoimmune diseases, and the
      possible role of autoantibodies in the etiopathogenesis of autoimmune disease.
      The antibodies associated with systemic rheumatic diseases serve as important
      tools in the initial diagnosis, and they are also useful in the evaluation of
      prognosis. However, for correct conclusions, the autoantibody findings should be
      carefully considered and interpreted in clinical context.

PMID- 8862681
TI  - Intraperitoneal chemotherapy in the treatment of ovarian cancer.
AB  - Over the past decade the intraperitoneal administration of chemotherapeutic
      agents has evolved from a pharmacokinetic concept into a rational treatment
      strategy for a selected group of women with advanced ovarian cancer. A recently
      reported large randomized controlled clinical trial has confirmed that the
      intraperitoneal administration of cisplatin is associated with superior efficacy
      and less toxicity than intravenous cisplatin in patients receiving initial
      chemotherapy for advanced small-volume residual ovarian cancer. Intraperitoneal
      chemotherapy is also a reasonable therapeutic option in women with very-small
      volume residual disease following an initial response to a platinum-paclitaxel
      systemic chemotherapy programme. On the basis of the data available to date,
      further exploration of a role for intraperitoneal chemotherapy in the management
      of ovarian cancer is indicated.

PMID- 8862682
TI  - Use of immunocytochemistry in the diagnosis of metastatic carcinoma.
AB  - Metastasis of unknown primary site is a common clinical problem.
      Immunohistochemistry has been shown to be a useful tool in the identification of
      the primary site. The availability of new antibodies specific for a wide range of
      antigens and working on routinely fixed, paraffin-imbedded material will ensure
      that this technique will continue to offer useful information in the search for
      an elusive primary tumour.

PMID- 8862683
TI  - Unravelling the molecular genetics of osteoarthrosis.
AB  - Osteoarthrosis (OA) is a major component of many osteochondrodysplastic syndromes
      which follow mendelian modes of inheritance. The use of molecular genetic
      techniques to unravel the molecular background of OA has therefore become
      possible. Linkage analysis, positional cloning, and candidate gene analysis have
      been used to identify genes which, when altered, can lead to syndromic OA. Allele
      association studies and sib-pair analysis have also made it possible to study the
      importance of a particular gene or locus in OA at the population level.
      Furthermore, the creation of transgenic mice and analyses of naturally occurring
      and chemically or radiologically induced mutations in mice are providing in vivo
      models for human osteochondrodysplasias and OA.

PMID- 8862684
TI  - Cytokeratin profile suggests metaplastic epithelial transformation in Barrett's
      oesophagus.
AB  - Cytokeratins are subunit proteins of epithelial cell intermediate filaments,
      which are genetically determined. Because epithelia have their own characteristic
      cytokeratin profile, this may reveal the origin of the epithelium. The
      cytokeratin profile of Barrett's oesophagus, complicating severe gastro
      oesophageal reflux disease, was determined in 35 consecutive patients and in 10
      normal controls in order to provide insight into the origin of Barrett's
      epithelium. Immunostaining of frozen sections showed abundant immunoactivity for
      cytokeratin (CK) 13, which is characteristic of squamous epithelia, including
      that of the oesophagus, but is not present in the simple columnar epithelium of
      the cardia. On the other hand, the latter epithelium expresses mainly CK 8, 18
      and 19, also found in Barrett's epithelium. The presence of CK 13 in Barrett's
      epithelium may indicate its origin from the squamous oesophageal epithelium and
      not from the proximal migration of columnar epithelial cells of the gastric
      cardia.

PMID- 8862685
TI  - Results of treatment in testicular nonseminoma.
AB  - Seventy-one testicular nonseminomatous germ cell tumours were treated in the
      Helsinki University Central Hospital between 1980 and 1990. Thirty-five (49%)
      were stage I, 16 (23%) stage II and 20 (28%) stage III tumours. The 5-year
      survival rates were 91%, 94% and 70%, respectively. Five of the eight patients
      relapsing in stage I had adverse histopathological risk factors in their tumours.
      In the retrospective evaluation two stage I patients had actually a higher stage.
      The good results in stage II were achieved with a routine combination of
      chemotherapy and retroperitoneal lymph node dissection. All five patients lost
      for stage III nonseminoma had risk factors for unfavourable prognosis: liver
      metastases or very high serum markers at diagnosis. The results presented here
      are considerably better than in the 1970s in this country and well comparable to
      results from countries where this malignancy is more common. Still some patients
      were lost. Co-operation in different fields of medicine is essential to find and
      treat optimally those with more aggressive disease and those who are cured with
      less strenuous treatment modalities.

PMID- 8862686
TI  - International variations in cardiovascular mortality associated with diabetes
      mellitus: the WHO Multinational Study of Vascular Disease in Diabetes.
AB  - The WHO Multinational Study of Vascular Disease in Diabetes was launched in 1975
      77 to investigate international variations in the occurrence of different
      manifestations of vascular disease in subjects with insulin-dependent and non
      insulin-dependent diabetes. A morbidity and mortality follow-up extending until
      January 1, 1988 was carried out in 10 centres, including five European centres
      (London, Switzerland, Berlin, Warsaw and Zagreb), two East Asian centres (Hong
      Kong and Tokyo), two Native American centres (Arizona and Oklahoma) and one
      Caribbean centre (Havana). Of a total of 4714 diabetic subjects (2310 men and
      2404 women) aged between 35 and 55 years at baseline who were successfully
      followed up, 1266 were classified as having insulin-dependent diabetes and 3448
      as having non-insulin-dependent diabetes. There was a large variation between the
      centres in ischaemic heart disease and cerebrovascular disease mortality rates
      for both insulin-dependent and non-insulin-dependent diabetic subjects,
      presumably reflecting in part differences between the background populations in
      mortality rates from these cardiovascular causes. The lowest ischaemic heart
      disease mortality rates for diabetic subjects were observed in Hong Kong and
      Tokyo centres, representing industrialized countries which have continued to have
      low ischaemic heart disease mortality rates. The importance of raised blood
      pressure and proteinuria as potentially modifiable cardiovascular risk factors in
      diabetic subjects was confirmed in this study.

PMID- 8862687
TI  - The impact of gender and general risk factors on the occurrence of
      atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus.
AB  - While it is generally accepted that non-insulin-dependent diabetes mellitus
      (NIDDM) increases atherosclerotic risk, controversy remains as to whether this
      effect is greater for women than men (thus reducing the usual gender
      differential). Furthermore, it is unclear to what extent changes in general risk
      factors may account for this increased risk. The literature was reviewed with
      meta-analyses. Gender specific overall relative risks with 95% confidence
      intervals for coronary heart disease (CHD) mortality (ICD codes 410-414) were
      calculated. Similarly, overall gender specific odds ratios for prevalent
      myocardial infarction (MI) are presented. Data are generated from both fixed
      effects and random effects models. Frequency counts of studies showing specific
      cardiovascular disease (CVD) risk factor effects in diabetes are given as is the
      number of studies showing diabetes to be an independent risk factor. The overall
      relative risk (the ratio of men to women) for CHD mortality in diabetes was 1.46
      (1.21-1.75) and 2.29 (2.05-2.55) in nondiabetes suggesting that the gender
      differential is reduced in diabetes. However, heterogeneity was high (P < 0.001).
      Exclusion of studies that were exclusively in elderly subjects eliminated
      heterogeneity (P > 0.05), but retained a separation of the confidence intervals.
      Overall odds ratios (men:women) show no suggestion of a diabetes effect on the
      gender difference for prevalent MI, 1.77 (diabetes) and 1.79 (no diabetes). The
      effects of six general CVD risk factors were unclear, although the largest study
      showed a clear effect of cholesterol, smoking, and blood pressure. All 10 studies
      in women report diabetes to be an independent risk factor as do 8 out of 12
      studies in men. NIDDM reduces the gender differential in CHD mortality, but not
      for prevalent MI (or other end points). Although the effect of specific CVD risk
      factors is inconsistent across studies, this is likely to reflect limited sample
      size and power. The major three risk factors, cholesterol, blood pressure, and
      smoking, probably operate in NIDDM but do not fully explain the increased risk of
      CVD in NIDDM.

PMID- 8862688
TI  - New insights into lipid metabolism in non-insulin-dependent diabetes mellitus.
AB  - Perturbations of lipid metabolism are common in diabetes. Therefore, an
      understanding of the underlying mechanism of lipid metabolism and in particular
      the role of insulin is a critical issue. The review aims to provide evidence that
      hypertriglyceridaemia is central to many features of diabetic dyslipidaemia.

PMID- 8862689
TI  - Lipids and lipoproteins as risk factors for coronary heart disease in non-insulin
      dependent diabetes mellitus.
AB  - Dyslipidaemia is frequent in non-insulin-dependent diabetes mellitus (NIDDM).
      Lipid and lipoprotein abnormalities include particularly elevated levels of total
      and very-low-density lipoprotein (VLDL) triglycerides and reduced levels of high
      density lipoprotein (HDL) cholesterol. The worsening of glycaemic control further
      deteriorates lipid and lipoprotein abnormalities and furthermore, total and low
      density lipoprotein (LDL) cholesterol levels are often elevated in poor glycaemic
      control. Epidemiological data show that total cholesterol is as powerful risk
      factor for coronary heart disease (CHD) in NIDDM patients as in nondiabetic
      subjects. High total triglycerides and low HDL cholesterol may be even stronger
      risk factors for CHD in NIDDM patients than in nondiabetic individuals, but more
      prospective studies are needed to substantiate this view. Compositional changes
      in LDL and VLDL particles may further increase the risk of CHD but
      epidemiological data are missing to support this notion.

PMID- 8862690
TI  - Modified lipoproteins, cytokines and macrovascular disease in non-insulin
      dependent diabetes mellitus.
AB  - The processes of glycation and oxidation play a significant role in the
      acceleration of atherosclerosis in diabetes mellitus. Glycation is thought not
      only to increase the susceptibility of low-density lipoprotein (LDL) to oxidation
      but also to enhance the propensity of vessel wall structural proteins to bind
      extravasated plasma proteins, including LDL, and thus to contribute to a more
      marked oxidative modification of LDL. Glycated and oxidized lipoproteins induce
      cholesteryl ester accumulation in human macrophages and may promote platelet and
      endothelial cell dysfunction. Furthermore, these modified lipoproteins have the
      ability to trigger an autoimmune response that leads to the formation of
      autoantibodies and subsequently to the formation of immune complexes containing
      LDL. Both the modified lipoproteins and the immune complexes formed with
      autoantibodies reactive with modified lipoproteins may be responsible for several
      alternative and not mutually exclusive pathways leading to foam cell formation,
      macrophage activation and endothelial cell damage and may thus be of potential
      significance in initiating and/or contributing to the acceleration of the
      development of atherosclerosis. In this review we discuss how modified LDL
      affects lipoprotein metabolism, how immune complexes containing LDL induce the
      transformation of macrophages into foam cells and promote macrophage activation
      leading to the release of cytokines and thus initiating a sequence of events
      leading to endothelial cell damage and to the recruitment and activation of
      leucocytes. We also summarize our work showing that macrophage activation by LDL
      containing immune complexes leads to a paradoxical increase in LDL-receptor
      expression thus further impairing cholesterol homeostasis and enhancing the
      development of atheromatous lesions.

PMID- 8862691
TI  - Will correction of dyslipoproteinaemia reduce coronary heart disease risk in
      patients with non-insulin-dependent diabetes? Need for trial evidence.
AB  - The incidence of atherosclerotic vascular disease is greatly increased in
      patients with non-insulin-dependent diabetes (NIDDM). The most frequent
      lipoprotein abnormalities in this type of diabetes are an increase in
      triglyceride-rich lipoproteins and a decrease in high-density lipoproteins.
      Hypertriglyceridaemia appears to be a stronger coronary heart disease risk factor
      in patients with NIDDM than in nondiabetic subjects. Plasma total and low-density
      lipoprotein cholesterol levels in NIDDM patients and nondiabetic subjects do not
      differ. Hypercholesterolaemia is, however, as powerful a predictor of coronary
      heart disease risk in diabetic patients as in nondiabetic subjects. In spite of
      this knowledge, there is to date no solid evidence to indicate whether correction
      of dyslipoproteinaemia in order to reduce coronary heart disease risk in patients
      with NIDDM is more, equally, or less beneficial than it is in nondiabetic
      subjects. The only available data come from post-hoc subgroup analyses of the
      Helsinki Heart Study and the Scandinavian Simvastatin Survival Study (4S). Other
      trials including patients with diabetes are in progress. Only one intervention
      trial (currently in its treatment phase), the Diabetes Atherosclerosis
      Intervention Study (DAIS), is specifically designed to examine the lipid
      hypothesis in patients with NIDDM.

PMID- 8862692
TI  - Cardiovascular risk factors and the prediabetic syndrome.
AB  - Cardiovascular disease is increased 2- to 4-fold in non-insulin-dependent
      diabetes mellitus (NIDDM); yet in most studies, there is a relatively weak
      relationship between the frequency of coronary heart disease (CHD) and the
      duration of diabetes and severity of hyperglycaemia. A number of authors have
      suggested that the prediabetic stage may contribute to the risk of CHD in NIDDM.
      Hyperinsulinaemia and insulin resistance have been strongly associated with the
      development of NIDDM. Data are less conclusive about the relationship of
      hyperinsulinaemia to the development of CHD in nondiabetic subjects. Relatively
      little data are available on hyperinsulinaemia and/or insulin resistance to CHD
      in NIDDM subjects. Tight control of glycaemia with exogenous insulin improves
      cardiovascular risk factors in NIDDM subjects and therefore is unlikely to
      increase the risk of CHD. Although the relation of insulin to CHD in the general
      population is somewhat controversial, insulin is clearly related to multiple
      cardiovascular risk factors (especially elevated triglyceride, decreased high
      density lipoprotein, small dense low-density lipoprotein, impaired glucose
      tolerance and increased plasminogen activator inhibitor 1 (PAI-1)). However, the
      relation of insulin resistance to hypertension remains controversial.

PMID- 8862693
TI  - Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin
      dependent diabetes mellitus.
AB  - Disturbances of the haemostatic system may favour the development of vascular
      damage and the final occlusion events in the progress of coronary heart disease
      (CHD). It has been shown recently in epidemiological studies, that increased
      concentration of several factors, mainly fibrinogen, factor VII, von Willebrand
      factor (vWF), and the fibrinolytic variables plasminogen activator inhibitor 1
      (PAI-1) and tissue plasminogen activator (t-PA), can be considered as risk
      factors for CHD. As morbidity and mortality through coronary atherosclerosis are
      higher in type 2 diabetic patients than in nondiabetic subjects and as insulin
      resistance represents a situation which favours the development of
      atherothrombosis, evaluation of the haemostatic factors which are recognized as
      risk factors may be interesting to consider in these situations. In fact, it has
      been shown that the fibrinolytic parameters PAI-1 and t-PA antigen are strongly
      related to the metabolic disorder of insulin resistance, whereas the link with
      fibrinogen, factor VII, and vWF remains weak. Many cross-sectional studies
      conducted in different populations have shown that PAI-1 and t-PA antigen (which
      represents t-PA/PAI-1 complexes) are strongly correlated with insulin,
      triglyceride, high-density lipoprotein (HDL) cholesterol, body mass index, walst
      to-hip ratio and blood pressure, and that the improvement of insulin resistance
      improves in parallel the metabolic abnormalities and the concentration of the
      fibrinolytic parameters. Attempts at explaining the elevated PAI-1 and t-PA
      antigen levels in the insulin resistance syndrome have involved many clinical and
      in vitro studies, in which the role of insulin, insulin propeptides, very-low
      density lipoprotein (VLDL) triglyceride, insulin resistance per se, glucose, and
      adipose tissue have successively been analysed and the main results of these
      studies are presented in this review. Due to recent experimental data from animal
      models of thrombosis, a pathogenic role of decreased fibrinolytic activity or
      increased PAI-1 levels can be proposed and could play a role in the development
      of vascular disease in subjects with Type 2 diabetes or insulin resistance.

PMID- 8862694
TI  - Comparison of the body composition of age-matched Italian, Ukrainian, and Dutch
      children.
AB  - In the present study, the body composition was measured in 35 Ukrainian children,
      14 boys and 21 girls, aged 8-12 years, by dual-energy X-ray absorptiometry
      (DEXA), anthropometry, and bioelectrical impedance. The results were compared
      with those obtained from a sample of the same number of Italian and Dutch
      children of the same sex and range of age. The Ukrainian children were slightly
      smaller, had a lower body weight, and had a lower body fat percentage, as
      measured by skinfolds, as compared with the Italian and Dutch children, as well
      as a lower calculated fat-free mass (FFM) by impedance. Comparison between FFM as
      determined by different methods in the Ukrainian children showed that all
      assessed values differed significantly. In particular, all methods overestimated
      the FFM as compared with DEXA, but the differences between DEXA and the other
      methods were not dependent on the level of FFM as determined by DEXA.
      Furthermore, the difference between predicted FFM and FFM values obtained by DEXA
      was correlated for skinfolds and body mass index (r = 0.77, p < 0.01), but not
      for body mass index and impedance, or skinfolds and impedance. The mean
      differences were 1.8 +/- 1.5 for body mass index, 1.0 +/- 1.4 for impedance, and
      3.6 +/- 1.6 for skinfolds. Some differences in the body composition have also
      been found between boys and girls. The boys had higher values of lean tissue
      (23.3 +/- 3.1 vs. 20.7 +/- 3.3; p < 0.01) and FFM (24.5 +/- 3.3 vs. 21.8 +/- 3.5;
      p < 0.01) as compared with the girls and slightly higher values of bone mineral
      content. It should be noted, however, that the differences between different
      groups and different methods are always small, even when they are statistically
      significant.

PMID- 8862695
TI  - Trends in food consumption in a south German population from 1984/85 to 1989/90:
      results from the WHO MONICA project Augsburg.
AB  - In the risk factor surveys of the WHO MONICA project Augsburg 1984/85 (S1) and
      1989/90 (S2), a qualitative food frequency questionnaire with 24 items was used
      to monitor trends in food consumption in two independent age- and sex-stratified
      two-stage cluster samples of the population aged 25-64 years (S1: n = 4,022; S2:
      n = 3,966). Alcohol intake was assessed by separate questions. From S1 to S2
      slight but encouraging trends towards a better agreement with dietary guidelines
      could be found with a decreasing monthly consumption of meat, sausages and ham,
      eggs, and beer and an increasing consumption of cooked vegetables and cereals.
      These trends correspond well with trends in food supply data.

PMID- 8862696
TI  - Promotion of IgA immune response in patients with Crohn's disease by oral
      bacteriotherapy with Lactobacillus GG.
AB  - The effect of oral bacteriotherapy with human Lactobacillus casei strain GG
      (10(10) colony-forming units twice daily for 10 days) was investigated in Crohn's
      disease and in juvenile chronic arthritis which are chronic inflammatory diseases
      associated with impaired mucosal barrier function. During oral bacteriotherapy,
      the gut immune response was indirectly assessed by solid-phase enzyme-linked
      immunoassay in 14 children with Crohn's disease, in 9 with juvenile chronic
      arthritis, and in 7 controls. The immunostimulatory effect of Lactobacillus GG
      was specific for Crohn's disease, irrespective of its activity: the mean (95%
      confidence interval) number of specific antibody secreting cells in the IgA class
      to beta-lactoglobulin increased significantly from 0.2 (0.04-1.3) to 1.4 (0.3
      6.0)/10(6) cells and to casein from 0.3 (0.1-1.4) to 1.0 (0.2-4.8)/10(6) cells.
      The results indicate that orally administered Lactobacillus GG has the potential
      to increase the gut IgA immune response and thereby to promote the gut
      immunological barrier. Consequently, Lactobacillus GG could provide an adjunct
      nutritional therapy for Crohn's disease.

PMID- 8862697
TI  - Influence of the intake of fortified breakfast cereals on dietary habits and
      nutritional status of Spanish schoolchildren.
AB  - A study was performed on the breakfast habits of 200 schoolchildren between 9 and
      13 years of age. The subjects were classified into two groups: group C, children
      who consumed fortified breakfast cereals (65 boys and 35 girls), and group NC,
      children who did not (64 boys and 36 girls). The different dietary habits and the
      nutritional status of the two groups were analyzed. Haematological, biochemical,
      anthropometric, and dietary data were collected, the latter involving a 5-day
      food record. The children of the C group were found not only to have a more
      complete and nutritive breakfast, but also showed better dietary patterns for the
      rest of the day. Their lipid intake (% kJ) was lower and the carbohydrate intake
      (g/d and % kJ) higher than in the NC children. The intakes of thiamine,
      pyridoxine, folates, and beta-carotenes were also higher in group C. Better
      dietary habits were reflected in higher blood levels of some important compounds.
      Group C children had higher retinol, serum folate, and riboflavin levels than NC
      children. The percentage of children with hypercholesterolaemia (serum
      cholesterol > 4.5 mmol/l) was higher amongst those of the NC group: 37% as
      compared with 18% of the C children.

PMID- 8862698
TI  - Increased secretion of triglyceride and cholesterol following inhibition of long
      chain fatty acid oxidation in rat liver.
AB  - The effects of emeriamine, a fungal metabolite and a potent inhibitor of
      mitochondrial fatty acid oxidation, on ketogenesis and lipid secretion were
      examined in isolated perfused livers from 2-day-fasted rats. Liver perfusion with
      increasing concentrations of emeriamine up to 3 mumol caused a dose-dependent
      inhibition of ketone body production. The hepatic uptake of exogenous oleic acid
      substrate was comparable in the control and emeriamine-treated livers. The
      addition of 2 mumol emeriamine to the perfusion medium at either the beginning of
      perfusion or 2 h later caused immediate and almost complete cessation of ketone
      body production, which was accompanied by a concomitant decrease in the beta
      hydroxybutyrate: acetoacetate ratio, suggesting a decreased production of NADH
      via mitochondrial beta-oxidation. Conversely, both triglyceride and cholesterol
      secretions were elevated, indicating a reciprocal response in ketogenesis and
      lipid secretion by the livers. The proportion of oleate in the perfusate
      triglyceride obtained from emeriamine-treated livers was significantly higher
      than that from control livers. In the post-perfused liver triglyceride, oleate
      was progressively increased in the livers treated with the inhibitor 2 h after
      perfusion and at the beginning of perfusion, respectively. These results indicate
      that direct inhibition of fatty acid oxidation diverts the exogenous fatty acids
      to the esterification pathway, and subsequently stimulate the synthesis and
      secretion of triglyceride and cholesterol. The fatty acid oxidation rate in the
      liver is, therefore, a critical determinant for the synthesis and secretion of
      these lipid components.

PMID- 8862699
TI  - Distribution of energy between food-restricted dams and offspring.
AB  - Pregnant and nonpregnant rats were subjected to one of four food intake
      schedules: ad libitum, 20, 40 and 60% of food restriction, during 20 days, with
      the objective of studying the distribution of energy between food-restricted
      mothers and offspring. The animals were anesthetized and the conceptuses were
      removed and separated into male, female, and placental tissues. The rats were
      then killed and all carcasses were prepared for energy balance determination. A
      baseline group of weight-matched rats were killed in the first day of the
      experiment to evaluate the initial body energy. The results obtained showed that
      the energy balance of pregnant rats was impaired as a consequence of the food
      restriction imposed. The offspring from restricted mothers had lower body weight
      and energy content and were less in number than the ones from the control dams.
      It is also suggested that food restriction causes the mother to transfer similar
      percent energy to the offspring as in control animals which will deplete the
      mother energy stores more than in ad libitum fed rats.

PMID- 8862700
TI  - The effect of alpha-linolenic acid-rich emulsion on fatty acid metabolism and
      leukotriene generation of the colon in a rat model with inflammatory bowel
      disease.
AB  - The purpose of this study was to investigate the efficacy of alpha-linolenic acid
      rich perilla oil emulsion (POE) in a rat model with trinitrobenzenesulfonic acid
      (TNB)-induced inflammatory bowel disease. Three different isocaloric solutions,
      which are glucose solution (FF), soybean oil emulsion (SOE) and POE, were infused
      for 14 days after instillation of TNB. After infusion, total cholesterol and
      phospholipid concentration in the plasma in the POE group were significantly
      decreased compared with the FF and SOE groups. Arachidonic acid level in the
      colonic phospholipids was significantly decreased and eicosapentaenoic acid level
      was significantly increased in the POE group compared with the FF and SOE groups.
      Thickness, damage score and leukotriene B4 content in the colon in the POE group
      were the lowest among the infusion groups. These results suggest that alpha
      linolenic acid suppresses the synthesis of leukotriene B4 in the colon by
      changing the fatty acid composition in the colonic phospholipids and that POE may
      be effective in the improvement of inflammation in the colon.

PMID- 8862701
TI  - Management of advanced breast cancer: patient needs, challenges and new treatment
      options. Introduction.

PMID- 8862702
TI  - Treatment of advanced breast cancer: current status.
AB  - Metastatic breast cancer is a major and increasing public health problem. The 5
      year survival for this disease is only 15%, and while hormonal and
      chemotherapeutic options have had a significant impact on long-term survival for
      patients with localized disease, treatment for disseminated disease remains
      essentially palliative. New treatment options are urgently needed to improve the
      prospects for patients with metastatic breast cancer, particularly for those with
      disease characteristics indicating a particularly poor prognosis. Docetaxel
      (Taxotere) is a promising new drug and has shown encouraging activity in patients
      with disease resistant to anthracyclines and in patients with visceral
      metastases, both of which indicate a poor prognosis. Although docetaxel is, at
      present, only licensed for use in patients with anthracycline-resistant disease,
      this highly active drug should now be developed for first-line treatment, and
      eventually for adjuvant use.

PMID- 8862703
TI  - First-line treatment of metastatic breast cancer.
AB  - Although metastatic breast cancer is an incurable disease, chemotherapy has had
      an impact on survival since the use of anthracycline drugs has become widespread.
      The optimal time for chemotherapeutic intervention for disseminated disease is in
      the first-line setting, but optimal treatments vary amongst patients, and the
      treatment must be chosen after consideration of the characteristics of the
      patient and the disease. Amongst the new drugs which have been used in the
      treatment of metastatic breast cancer, vinorelbine and the taxoids, docetaxel
      (Taxotere) and paclitaxel (Taxol), challenge monotherapy with anthracycline
      drugs, and even combination therapies, with regard to the response rate
      obtainable. In five multicentre phase II trials, the response rate to docetaxel,
      75 or 100 mg/m2, given intravenously over 1 hour every 3 weeks, varied from 38 to
      68%, with a median survival of 16.4 months across all studies. Good performance
      status and treatment with the higher dose improved response rates, though these
      effects were not statistically significant. Docetaxel has proved to be a highly
      active monotherapy for metastatic breast cancer in the first-line setting.

PMID- 8862704
TI  - Treatment of patients resistant to anthracycline therapy.
AB  - The results of three multicentre phase II trials in which docetaxel (Taxotere)
      was used in previously treated patients with metastatic breast cancer resistant
      to anthracyclines or anthracenediones are summarized here. Docetaxel was given to
      a total of 134 patients who had evidence of disease progression while receiving
      anthracyclines or anthracenediones for metastatic disease or had relapsed during
      adjuvant therapy which included these agents. The overall response rate (ORR)
      across the three studies was 41% in an intent-to-treat analysis. The median
      duration of response varied from 24 to 28 weeks between studies and the median
      survival varied from 9 to 12 months. The response rate was well maintained in
      evaluable patients with visceral metastases (ORR 43%), or multiple (> 2) sites of
      disease (ORR 48%). These response rates are the highest ever reported for a
      single agent in patients with anthracycline-resistant disease. The recommended
      dose and schedule for docetaxel (100 mg/m2 intravenously over 1-h every 3 weeks),
      which was used in all three studies, was found to be well tolerated, with
      neutropenia as the most common toxicity (grade 4 in 90% of patients) and febrile
      neutropenia requiring hospitalisation occurring in only 4% of cycles of therapy.

PMID- 8862706
TI  - Treatment of patients with liver metastases.
AB  - The presence of liver metastases is considered a very poor prognostic factor for
      patients with metastatic breast cancer. Liver metastases are generally considered
      to be less responsive to chemotherapy than metastases in other sites, and
      patients with liver lesions have a shorter survival duration than patients with
      other sites of disease. The results from five multicentre phase II studies of
      docetaxel (Taxotere) as a first-line treatment for metastatic breast cancer have
      been analysed with regard to the presence or absence of liver lesions, which were
      found in 39% of the 209 patients involved. Response rates to docetaxel, 100 or 75
      mg/m2, were maintained in the presence of liver lesions and the median survival
      across all five studies was 16.4 months for all patients and 14.7 months for
      patients with liver lesions. Similarly, when results from 129 patients given
      docetaxel as a second-line treatment were analysed, the response rates and
      survival durations were not reduced in the 57% of patients who had liver lesions.
      These results indicate that the presence of liver metastases does not reduce the
      probability or duration of response to docetaxel as a first- or second-line
      treatment for advanced breast cancer.

PMID- 8862705
TI  - Treatment of patients resistant to paclitaxel therapy.
AB  - Although the taxoid drugs, paclitaxel (Taxol) and docetaxel (Taxotere) have a
      broadly similar mechanism of action, there are notable differences in their
      activities and they are distinct agents. Docetaxel is more potent than paclitaxel
      with regard to the promotion of the polymerization of tubulin and the inhibition
      of depolymerization, and has greater antitumour activity in many in vitro and in
      vivo tumour model systems. The development of drug resistance is a major problem
      in the treatment of metastatic breast cancer and observations indicating only
      partial cross-resistance between docetaxel and paclitaxel in vitro, combined with
      supporting clinical evidence of activity in patients with previously-treated
      tumours, including anthracycline-resistant breast cancer, led to the
      implementation of a prospective study of docetaxel treatment in patients with
      paclitaxel-resistant disease. Preliminary results in 27 patients recruited to
      this ongoing study indicate that docetaxel has activity in paclitaxel-resistant
      metastatic breast cancer.

PMID- 8862707
TI  - Optimal use of docetaxel (Taxotere): maximizing its potential.
AB  - The safety of docetaxel (Taxotere) has been evaluated in the safety overview
      population consisting of 1070 patients recruited to phase II trials. These
      patients received a total of 4989 cycles of therapy (median four cycles per
      patient). Since docetaxel is known to be metabolized in the liver, hepatic
      impairment was predicted to be a risk factor for increased toxicity and was
      studied prospectively, comparing the 42 patients in the overview population with
      moderate hepatic impairment with the 1028 patients with liver function within
      normal limits. Hepatic dysfunction was associated with an increase in the
      percentage of cycles of therapy during which febrile neutropenia occurred and the
      number of patients suffering documented infection and severe (grade 3/4)
      stomatitis. The incidence of toxic death was also increased in patients with
      moderate hepatic impairment. The severity of fluid retention, a cumulative
      toxicity of docetaxel, was found to be reduced, and its onset delayed, by
      prophylactic treatment with corticosteroids for 5 days, starting 1 day before
      docetaxel administration. Treatment with corticosteroids was also recommended to
      reduce the incidence and severity of hypersensitivity reactions and cutaneous
      toxicities. The most frequent severe non-haematological toxicity of docetaxel was
      asthenia. Other non-haematological toxicities were generally mild or moderate.

PMID- 8862708
TI  - The development of new chemotherapeutic agents.
AB  - There is a great need for new drugs to treat the increasing numbers of patients
      with disseminated cancers. Many of the known anticancer drugs, including the
      taxoids, docetaxel (Taxotere) and paclitaxel (Taxol), are derived from natural
      products and there will be many more active compounds to be discovered amongst
      the 300000 plant species available for evaluation. Cytotoxic agents may kill
      cancer cells by a variety of means. Thymidilate synthase inhibitors such as
      LY231514 and raltitrexed (Tomudex) have shown activity against a variety of solid
      tumours including colorectal cancer. The antifolate, trimetrexate, and the
      nucleoside analogue, gemcitabine, have also shown anticancer activity. Amongst
      the topoisomerase I inhibitors, CPT-11 is being developed for use against
      colorectal cancer. Non-cytotoxic agents which interfere with processes such as
      angiogenesis may also have a role in future treatments for disseminated cancers.

PMID- 8862709
TI  - The scientific rationale for developing taxoids.
AB  - The taxoid drugs, docetaxel (Taxotere) and paclitaxel (Taxol), represent a new
      class of antitumour agents which act by promoting the assembly and inhibiting the
      disassembly of microtubules. Docetaxel has been shown to be more potent than
      paclitaxel with regard to the formation and stabilization of microtubules in
      vitro. Docetaxel also has a higher cell uptake than paclitaxel and a longer
      intracellular retention time. Docetaxel is a more potent antitumour agent than
      paclitaxel in most model systems. The observation that the cytotoxic
      concentration for docetaxel is lower than that for paclitaxel in cultures of
      human haematopoietic cells supports the clinical observation that dose-limiting
      neutropenia is seen at a lower dose of docetaxel than paclitaxel. The
      concentration of docetaxel required to kill tumour cells in vitro is well within
      the plasma concentrations recorded in clinical studies, and docetaxel has shown
      extensive clinical activity against a variety of solid tumours. Most drugs are
      used in combination regimens in the clinic and combinations of docetaxel with
      other agents are under active investigation. The agents to be combined with
      docetaxel include those which showed synergism with docetaxel in vitro and can be
      delivered at optimal doses without additive toxicity.

PMID- 8862710
TI  - The clinical rationale for developing docetaxel (Taxotere).
AB  - Clinical empiricism has recognized resistant breast cancer as a privileged target
      for docetaxel (Taxotere). This worldwide registration will offer medical
      oncologists the opportunity to develop new indications for docetaxel.
      Pharmacokinetics, preclinical optimal combination and clinical practice will
      constitute the rationale for the future development of docetaxel.

PMID- 8862711
TI  - New approaches to the treatment of advanced breast cancer.
AB  - The increase in our understanding of the mode of action of drugs and their
      potential interactions is allowing treatment strategies to be designed to
      optimize efficacy and minimize toxicity. Combination chemotherapy may entail the
      use of concurrent administration of two or more agents, or sequential or
      alternating administration of single agents or combinations. It is increasingly
      important to understand the advantages and disadvantages of each of these
      strategies, and the influence of each component of a combination therapy.
      Biochemical modulation is now used to enhance drug efficacy: the metabolism of 5
      fluorouracil can be modified using leucovorin, methotrexate and 5-ethynyluracil;
      etoposide enhances the action of platinum drugs by inhibiting repair of the
      platinum-damaged DNA; and treatment with topoisomerase I inhibitors can increase
      sensitivity to topoisomerase II inhibitors. The role of docetaxel in combinations
      is now under investigation. Docetaxel (Taxotere) has the following features which
      indicate that it will be a useful drug in combination: the unique mechanism of
      action of the taxoids; neutropenia as the single dose-limiting toxicity; and a
      broad spectrum of antitumour activity. Clinical trials are ongoing to examine the
      use of docetaxel combination regimens in several disease areas.

PMID- 8862712
TI  - Taxoids in combination chemotherapy for metastatic breast cancer.
AB  - The rationale for the development of new drug combinations is to combine optimal
      doses of drugs with single agent activity which are not cross-resistant and have
      non-overlapping toxicities. Anthracyclines are widely accepted as the agents of
      choice for first-line treatment of metastatic breast cancer and have been tested
      in combination with the taxoids, docetaxel (Taxotere) and paclitaxel (Taxol).
      Toxicity problems have emerged using anthracyclines and paclitaxel, with sequence
      and schedule-dependent toxic effects including dose-limiting typhlitis and
      mucositis, as well as febrile neutropenia and, in one study, cardiomyopathy. The
      dose-limiting toxicities of the combination of docetaxel and doxorubicin are
      neutropenia and infection, and preliminary results indicate a response rate of
      89%. There is a need to develop a combination treatment regimen which is non
      cross-resistant with anthracyclines. Vinorelbine (Navelbine) has single agent
      activity against metastatic breast cancer and has been used in combination with
      taxoids. The dose-limiting toxicities of the vinorelbine-paclitaxel combination
      are febrile neutropenia, pelvic pain, fatigue and paraesthesias. The dose
      limiting toxicities of the combination of docetaxel and vinorelbine are febrile
      neutropenia and mucositis. The overall response rate for this combination was 67%
      and studies are ongoing.

PMID- 8862713
TI  - Conclusion: the place of docetaxel (Taxotere) in future therapy.

PMID- 8862714
TI  - Remission of refractory gestational trophoblastic disease with high-dose
      paclitaxel.
AB  - High-risk metastatic gestational trophoblastic disease (GTD) in patients who have
      failed primary chemotherapy has a very poor prognosis. About 25% of women with
      high-risk metastatic disease become refractory to EMA-CO (etoposide,
      methotrexate, actinomycin-D, cyclophosphamide and vincristine) and fall to
      achieve a complete remission. Currently, there is no standard salvage
      chemotherapeutic regime for EMA-CO failure. Paclitaxel, a taxane analog extracted
      from the bark of the western yew (Taxus brevlfolla), has shown antitumor activity
      in a variety of cancer cell lines. High in vivo efficacy was confirmed in phase
      II trials, especially for breast and epithelial ovarian cancer patients.
      Recently, two in vitro studies have shown that paclitaxel is a highly effective
      antineoplastic agent in choriocarcinoma cell lines. We present the first clinical
      report of a serologic remission with high-dose paclitaxel (250 mg/m2 i.v.
      infusion over 24 h every 3 weeks) of a highly refractory GTD in a patient who
      developed brain metastasis after multiple combined chemotherapeutic regimens. The
      patient tolerated paclitaxel with granulocyte colony stimulating factor support
      very well. The remission with paclitaxel in this patient confirms its preclinical
      activity in high-risk, refractory GTD.

PMID- 8862715
TI  - Drug retention following intravesical delivery of fluorouracil therapeutic
      adhesive in C3H mouse bladder.
AB  - We have developed a fibrinogen-based, sustained-retention drug delivery system,
      therapeutic adhesive (TA), for application to resected tumor beds to reduce local
      tumor recurrences. In this study we evaluated the feasibility, safety and
      retention of the TA formulated with 5-fluorouracil (5-FU TA) after intravesical
      administration in a mouse bladder model. Radiolabeled [14C]5-FU TA or [14C]5-FU
      solution was delivered intravesically to C3H/He female mice. After drug
      administration, retention of 14C in the bladder was quantified by storage
      phosphor autoradiography. A 2.6-fold increase in retention was observed with 5-FU
      TA when compared with 5-FU solution. The AUC(2 min-5 h) for 5-FU TA was 685 nmol
      h/mm2 compared with 260 nmol h/mm3 for 5-FU solution. No signs of toxicity in the
      bladder tissue or treatment-associated adverse effects were observed in the mice.

PMID- 8862716
TI  - Cytogenetic analysis in peripheral lymphocytes of cancer patients treated with
      cytostatic drugs: results from an EC Collaborative Study.
AB  - Many of the cytostatic drugs commonly used in cancer chemotherapy treatments have
      been shown to be genotoxic in vivo and in vitro. We present a cytogenetic
      collaborative study on 13 cancer patients treated with different antitumor
      agents. For comparison we also carried out a cytogenetic analysis on 14 healthy
      untreated controls. The frequency of sister chromatid exchanges and structural
      chromosome aberrations in peripheral blood lymphocytes of the cancer patients was
      determined prior to the treatment, just after it and 3-7 weeks later. The results
      obtained show clear differences between the basal levels of cytogenetic
      alterations in cancer patients, even though the mean value is higher in this
      group than the basal levels of the group of healthy individuals. Treatment with
      cytostatics increases the frequency of both cytogenetic biomarkers analyzed,
      which declined to values similar to those initially observed several weeks after
      the treatment. Our data are in qualitative and quantitative agreement with other
      results previously found by other authors.

PMID- 8862718
TI  - A prospective cohort study of the effect of vincristine on audition.
AB  - We conducted a prospective cohort study of the possible ototoxic effect of
      vincristine among patients treated for lymphoproliferative malignancies. No
      deleterious effect of moderate doses of vincristine on pure tone audiometry for
      air and bone conduction and on speech audiometry could be found. Nevertheless,
      the isolated finding of sensorineural hearing loss in the only patient who
      received a high dose of vincristine raises the issue of ototoxicity as a possible
      dose-related and dose-limiting side effect of vincristine.

PMID- 8862717
TI  - A phase I trial of 5-fluorouracil, leucovorin and interferon-alpha 2b
      administered by 24 h infusion in metastatic colorectal carcinoma.
AB  - A phase I trial of 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN)
      was conducted in 15 advanced colorectal cancer patients refractory to a bolus
      regimen of 5-FU/LV. Therapy consisted of a weekly i.v. infusion of 5-FU at 2600
      mg/m2 administered concomitantly with LV at 500 mg/m2 over a 24 h period. IFN
      alpha 2b was administered by 24 h infusion from the second cycle at escalating
      dose (4.5, 9, 18 and 27 MU/m2). The maximum tolerated dose of IFN was 18 MU/m2.
      At 27 MU/m2 two patients complained of diarrhea grade 3, so that the escalation
      of IFN dose was stopped. Two patients achieved a partial response (IFN level dose
      9-18 MU/m2). Eight patients had stable disease. Pharmacokinetics of 5-FU were not
      influenced by IFN at any level dose. Our results show that doses of IFN of 18
      MU/m2 given by a 24 h infusion can be administered safely to an established and
      active schedule of weekly 24 h infusion of 5-FU and LV. A phase II study has been
      planned to define the level of activity of this regimen.

PMID- 8862719
TI  - A phase II trial of piroxantrone in endometrial cancer: Southwest Oncology Group
      study 8918.
AB  - A phase II trial of the new anthrapyrazole piroxantrone was carried out by the
      Southwest Oncology Group in patients with advanced metastatic or recurrent
      endometrial cancer. A two-stage statistical design targeted accrual of 20
      eligible patients. The starting dose of piroxantrone was 150 mg/m2 in patients
      without prior radiation therapy (RT) and 120 mg/m2 in patients with prior RT.
      There were 15 eligible patients, six of whom had received prior hormonal therapy
      while nine patients had not received prior hormonal therapy. Eight patients had
      received prior RT while seven patients had not received any prior RT. One to
      seven cycles of piroxantrone were administered. Dose escalation was feasible in
      four patients. No grade 5 toxicity was experienced by any patients. Most of the
      grade 4 (granulocytopenia in one) and grade 3 (leukopenia in three,
      granulocytopenia in three, anemia in two and thrombocytopenia in one) toxicity
      was related to myelosuppression. Grade 3 non-hematologic toxicities were nausea,
      fatigue and SGOT elevation. There was one partial response for a response rate of
      7% (95% CI 0.2-32%) and median survival was 11 months (95% CI 3-13 months). The
      study was prematurely terminated due to lack of patient accrual.

PMID- 8862720
TI  - Interactions between taxol and camptothecin.
AB  - Taxol is an antitumor drug which, as its mechanism of action, promotes
      microtubule assembly in vitro. Camptothecin (CPT) is an anticancer agent with the
      peculiar mechanism of poisoning eukaryotic DNA topoisomerase I. Both drugs are in
      clinical trials and their chemotherapeutic efficacy seems promising in refractory
      human ovarian cancer. We studied the molecular and cellular pharmacology of the
      two drugs when administered simultaneously toward human ovarian cancer cell line
      A2780. Taxol inhibits CPT-induced single-strand breaks as well as CPT-induced
      cytotoxicity. Taken together, our experiments indicate that the two drugs might
      interact with the same class of nuclear enzyme, i.e. DNA topoisomerase I.

PMID- 8862721
TI  - Antiemetic treatment with two different doses of methylprednisolone in breast
      cancer patients: a double-blind randomized cross-over study with evaluation of
      efficacy parameters.
AB  - This randomized double-blind cross-over study followed a previous one which
      showed an antiemetic efficacy from methylprednisolone (MP) 250 mg superior to
      placebo. The present study compared MP 40 mg with 250 mg in breast cancer
      patients treated with non-cisplatin chemotherapy. Preference after course II was
      the determining parameter. Participation in two courses was compulsory for
      evaluation, participation in four courses was optional. Interim analyses were
      performed after each 12 patients to a maximum of 60 patients. As there was no
      significant difference in preference in 60 patients the study was closed.
      Patients treated with the CEF regimen, patients who requested rescue antiemetics
      and patients completing four study courses had a better effect from high-dose MP
      reflected in preference and other parameters. Global assessments, measurement of
      emetic volumes and the visual analog scale for nausea gave a fair coherence with
      patients' preference. The numbers of emetic episodes and observer registered
      nausea were of no value. The stability of preference and other parameters after
      course II and IV, respectively, was low. The present study did not prove
      superiority from high-dose MP. This hypothesis must be tested in patients more
      severely bothered by emesis after chemotherapy. These results show the complexity
      of evaluation of antiemetic effect and demonstrate the dependency of a given
      result on the parameter used.

PMID- 8862722
TI  - Daily oral etoposide in metastatic breast cancer.
AB  - Etoposide, administered i.v. or orally, as a single agent, in 1- to 5-day
      courses, was found to be minimally effective in pretreated advanced breast cancer
      patients. Clinical data suggested an effectiveness of a chronic low-dose oral
      etoposide schedule, in refractory and those malignancies otherwise unresponsive
      to the drug. Therefore, the aim of our open-labeled, non-randomized, phase II
      clinical study was to investigate the efficacy and toxicity of chronic daily
      etoposide (50 mg/m2 daily, for 21 consecutive days, every 28 days) as a first
      line chemotherapy for metastatic breast cancer. Twenty-one advanced breast cancer
      patients, with or without previous adjuvant CMF chemotherapy, were included. One
      complete (CR) and five partial remissions (PR) were obtained in 18 patients
      evaluable for response. Disease stabilization was obtained in 10 patients (55%),
      while two patients (11%) failed to respond. Grade 3-4 hematological toxicity
      developed in seven out of 21 patients evaluable for toxicity or in 15 out of 96
      cycles. Nonhematological toxicity was moderate. Our results showed the efficacy
      and relative low toxicity of a chronic oral etoposide regimen in advanced breast
      cancer patients. Adjuvant CMF chemotherapy did not influence the therapeutic
      response. Previous irradiation of the breast tended to increase the etoposide
      hematological toxicity.

PMID- 8862723
TI  - Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed
      to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two
      biochemical modulators.
AB  - We have focused our attention on the development of a novel form of a tegafur
      based [FT; a prodrug of 5-fluorouracil (5-FU)] antitumor agent. We have used two
      biochemical and pharmacological modulators of 5-FU to improve its overall
      activity. To potentiate the antitumor activity of FT, 5-chloro-2,4
      dihydroxypyridine (CDHP) was used as a potent reversible inhibitor of 5-FU
      degradation. The reduction of gastrointestinal (GI) toxicity, induced in the host
      by 5-FU, was modulated by potassium oxonate (Oxo), an inhibitor of orotate
      phosphoribosyltransferase that catalyzes the phosphorylation of 5-FU, a process
      believed to be responsible for the toxic effects of 5-FU. When CDHP and FT were
      simultaneously given orally to Yoshida sarcoma-bearing rats in various molar
      ratios, the antitumor effect of FT was significantly potentiated by the
      combination consisting of at least a 0.2 versus 1 molar ratio of CDHP to FT,
      respectively. This augmentation of an antitumor activity was supported by potent
      and prolonged inhibition of dihydrouracil dehydrogenase activity (5-FU degrading
      activities) in the liver of tumor-bearing rats after oral CDHP (0.2:0.8 molar
      ratio) and furthermore by elevation and over 12 h retention of 5-FU levels in the
      tumors following combined administration of FT and CDHP at a molar ratio of
      1:0.4, respectively. Moreover, to reduce the severe GI injury and subsequent loss
      of body weight, observed in parallel with an increased antitumor efficacy, Oxo
      was given orally to Yoshida sarcoma-bearing rats and nude rats xenografted with H
      81 human gastric carcinoma, during consecutive administration of the FT-CDHP
      mixture. Combined treatment with Oxo and FT (1:2 molar ratio) supplemented with
      0.4 molar CDHP resulted in protection of body weight loss without affecting the
      high antitumor efficacy of the FT-CDHP mixture. When [2-14C]FT plus CDHP was
      administered with Oxo, the 14C-labeled fluoronucleotide content was objectively
      decreased in the GI tract of the tumor-bearing rats but not in the tumor and bone
      marrow, which supports our initial hypothesis. Based on these promising data, we
      propose a suitable formulation of a FT-based anticancer drug, called S-1, and
      consisting of FT, CDHP and Oxo at a 1:0.4:1 molar ratio and showing tumor
      selective cytotoxicity of 5-FU.

PMID- 8862724
TI  - The effect of dexrazoxane (ICRF-187) on doxorubicin- and daunorubicin-mediated
      growth inhibition of Chinese hamster ovary cells.
AB  - Dexrazoxane (ICRF-187) is clinically used to reduce doxorubicin-induced
      cardiotoxicity. Because dexrazoxane, doxorubicin and daunorubicin all act on DNA
      topoisomerase II, a study was undertaken to see what effect dexrazoxane had on
      the growth inhibitory effects of doxorubicin and daunorubicin towards Chinese
      hamster ovary cells. Dexrazoxane exhibited significant antagonism of doxorubicin-
      and daunorubicin-mediated growth inhibition when the cells were preincubated with
      dexrazoxane before the anthracycline was added. Continuous exposure of cells to
      either anthracycline and low concentrations of dexrazoxane resulted in additive
      growth inhibitory effects at low anthracycline concentrations, and no effect at
      higher anthracycline concentrations.

PMID- 8862725
TI  - Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry
      screening assay.
AB  - In order to compare the capacities of a variety of compounds to interfere with P
      glycoprotein (Pgp) function, a novel assay was set up to work on a large
      screening scale. The model assay measures the capacity of parental sensitive
      (Par) and multidrug-resistant (MDR) cells to efflux a small fixed amount of
      acetoxymethyl calcein (calcein-AM) after their pretreatment with concentration
      ranges of known Pgp modulators. This microplate cytometry-based assay was
      performed with two different pairs of cell lines, the human lymphocytic leukemia
      CEM cells and the murine monocytic leukemia P388 cells. For a given Pgp
      expressing MDR cell line, a Pgp modulator EC50 was defined as the concentration
      required to restore half of the calcein retention shown by similarly treated Par
      cells. With both MDR-P388 and MDR-CEM cells, EC50 comparisons ranked five
      reference Pgp modulators as follows: SDZ 280-446 > SDZ PSC 833 > cyclosporin A >
      verapamil > vinblastine. Further use of the MDR-CEM cells could rank 15 Pgp
      modulators for their capacity to interfere with calcein-AM efflux as follows: SDZ
      280-446 1.9 x > SDZ PSC 833 8.3 x > cyclosporin A 3.8 x > amiodarone 1.1 x >
      quinacrine 1.6 x > verapamil 1.4 x > quinidine 1.1 x > vinblastine 11 x >
      vincristine 2 x > chloroquine > beta-lumicolchicine > or = gamma-lumicolchicine >
      or = colchicine > etoposide > or = doxorubicin. This calcein-AM assay should open
      the way for ranking large numbers of novel structures for their potential Pgp
      modulator properties, particularly for an efficient screening of Pgp function
      antagonists, but it does not allow defining whether their inhibition may be
      competitive or not.

PMID- 8862726
TI  - A quantitative morphometric study of the kinetics of tissue regeneration after
      administration of cisplatin.
AB  - The effect of the anti-neoplastic drug cisplatin was investigated on several rat
      tissues using a novel computerized morphometric image analysis system. The rats
      were sacrificed in pre-determined intervals, ranging from 1 to 36 days after drug
      administration, and their liver, kidneys and external ears were sampled and
      sectioned. Tritiated thymidine was injected into each rat 1 h prior to sacrifice
      to enable autoradiographical explorations. All sections were
      histomorphometrically studied by a computerized system. The kidneys of the
      experimental group revealed increased tubular diameters, especially in the
      corticomedular region. In the ears, decreases of the mean epithelial thickness,
      in the mean number of nuclei and in the mean nuclear surface were observed. The
      thickness of the connective tissue also decreased significantly by the end of the
      first week and returned to its normal size later on. No changes were detected in
      the ear cartilage. In the liver, no morphometrical differences were noticed in
      the hepatocyte density, Kupffer cell density or nuclear area. The nuclei of the
      hepatocytes and Kupffer cells retained a constant ratio to the total number of
      cells throughout the whole experiment. Liver autoradiography revealed that the
      hepatocyte and Kupffer cell labelling indexes after cisplatin administration were
      significantly higher than those of the control group, indicating enhanced
      replication of cells and increased synthesis of DNA, which in turn is accumulated
      in the nuclei and turn the cells into polyploids. In addition, the mean radius of
      the liver acini after cisplatin was diminished, followed by a significant
      reduction in the size of the progenitor compartment. It is concluded that while
      the kidneys are the organs most affected by cisplatin, the progenitor compartment
      of the liver is heavily affected as well. Computerized morphometry was
      demonstrated as a highly reproducible and accurate quantitative method for
      evaluation of histopathological changes in various mammalian tissues.

PMID- 8862727
TI  - The influence of hypoxia on the cytotoxicity of concomitant KW-2149 and ionizing
      irradiation in Chinese hamster fibroblasts.
AB  - 7-N-((2-((2-(gamma-L-glutamylamino)ethyl)dithio)ethyl))-mitomycin C (KW-2149) is
      a newly synthesized water-soluble mitomycin C (MMC) analog. Preclinical testing
      showed an interesting activity profile and a superior hematological tolerance in
      murine models. The aim of this study was to investigate the interaction of this
      compound with ionizing radiation, both under normoxic and hypoxic conditions, in
      Chinese hamster fibroblasts (V79). V79 cells were irradiated both under normoxic
      conditions and after a 1 h period of hypoxia. Paired irradiation dose-response
      curves confirmed the significance of radioresistance under hypoxia with an oxygen
      enhancement ratio of approximately 3. In contrast to MMC, KW-2149 showed no
      increased cytotoxic effect on hypoxic V79 cells. The cytotoxic effect of KW-2149
      increased with increasing concentration, irrespective of the ambient oxygen
      pressure. When KW-2149 was combined with irradiation under hypoxic conditions,
      cytotoxicity was significantly enhanced under these conditions. The difference in
      survival between normoxic and hypoxic conditions was statistically significant (p
      < 0.004). These data suggest a radiosensitizing effect of KW-2149, more
      pronounced under hypoxic conditions. This effect increases with radiation dose.
      It also corroborates earlier suggestions of a different mode of action of KW-2149
      as compared to MMC.

PMID- 8862728
TI  - Antitumor activity of 2-amino-4,4 alpha-dihydro-4 alpha, 7-dimethyl-3H
      phenoxazine-3-one, a novel phenoxazine derivative produced by the reaction of 2
      amino-5-methylphenol with bovine hemolysate.
AB  - 2-Amino-4,4 alpha-dihydro-4 alpha,7-dimethyl-3H-phenoxazine-3-one (Phx) was
      synthesized by the reaction of 2-amino-5-methyl-phenol with bovine hemolysates.
      Since Phx is a phenoxazine derivative like actinomycin D, which exerts a strong
      anti-tumor effect by intercalating DNA, we examined the effects of Phx on cell
      proliferation and cell cycle progression in human epidermoid carcinoma cells (KB
      cells). Phx inhibited the proliferation of Kb cells in a dose-dependent manner.
      When KB cells were incubated for 9 h with medium containing 50 microM Phx, a
      transient accumulation of cells in S and G2/M phase was observed and at 24 h many
      of cells had lower DNA content. Although Phx had antitumor activity, the drug did
      not intercalate DNA, showing a different mode of action from actinomycin D.

PMID- 8862729
TI  - Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution
      of doxorubicin after intraperitoneal administration.
AB  - Increased hydrostatic pressure in solid tumor nodules decreases the penetration
      of chemotherapy into cancerous tissue. This is true for both i.v. and i.p.
      chemotherapy. The purpose of this study was to determine the influence of
      increasing intra-abdominal pressures on the pharmacokinetics and tissue
      distribution of doxorubicin administered i.p. Four groups of 10 Sprague Dawley
      rats were given i.p. doxorubicin (4 mg/kg) during 60 min combined with no
      pressure (control), 10, 20 and 30 mm Hg pressures. During the course of i.p.
      chemotherapy, peritoneal fluid and blood were sampled. Two other groups of 10
      rats received the same dose of i.p. doxorubicin during 10 min combined with no
      pressure and 30 mm Hg pressure. At the end of experiments animals were sacrificed
      and tissue samples were collected. Doxorubicin concentrations in peritoneal
      fluid, plasma and tissues were determined by HPLC. Pharmacokinetic studies showed
      that increased intra-abdominal pressures of 10, 20 and 30 mm Hg did not alter
      peritoneal fluid AUCs, the plasma AUCs and the peak ratios of i.p. doxorubicin
      when compared to the control group (no pressure). A subset analysis of high intra
      abdominal pressure groups (20 and 30 mm Hg) versus control group showed
      statistically significant differences in peritoneal fluid AUCs, plasma AUCs and
      AUC (peritoneal fluid/plasma) ratios. For all groups, the highest tissue
      concentrations of doxorubicin were found in tissues associated with the parietal
      peritoneum: the bladder, the abdominal wall and the diaphragm. After 10 min of
      i.p. chemotherapy, the group treated with 30 mm Hg pressure showed a significant
      increase of doxorubicin concentrations in these tissues as compared to the
      control group. This significant increase of tissue doxorubicin concentrations was
      not found after 60 min of pressure with i.p. chemotherapy; prolonged intra
      abdominal pressure was associated with a high incidence of intestinal ischemia.
      In conclusion, intra-abdominal pressure of 20 and 30 mm Hg significantly
      decreased the AUC ratios of i.p. doxorubicin but concomitantly increased tissue
      uptake of doxorubicin in bladder, diaphragm and abdominal wall during the first
      10 min of i.p. administration. These findings may have significance in the design
      of improved strategies to increase tissue concentrations of chemotherapy
      delivered by an i.p. route.

PMID- 8862730
TI  - Modulation of melphalan cytotoxic activity in human melanoma cell lines.
AB  - The aim of the present study was to potentiate the cytotoxic effects of melphalan
      through pharmacological and physical modulators. The combination of the cytotoxic
      agent with ethacrynic acid, a glutathione-S-transferase pi (GST pi) inhibitor, or
      topotecan, a topoisomerase I inhibitor, or mild hyperthermia was investigated.
      The selected cell lines exhibited variable levels of expression of GST pi, DNA
      topoisomerase I and heat-shock proteins. Mild hyperthermia (42 degrees C) alone
      potentiated melphalan cytotoxicity, especially in the two cell lines exhibiting
      low basal levels of HSP70 expression. The combination of the GST inhibitor with
      melphalan resulted in a potentiation of drug cytotoxicity only in JR8 cells, one
      of the two cell lines which expressed high levels of GST pi mRNA and which were
      the less responsive to ethacrinic acid alone. A synergistic interaction between
      topotecan and melphalan was observed only in the cell lines expressing low levels
      of topoisomerase I even if all cell lines exhibited a comparable sensitivity to
      this agent. The results support an involvement of GST and DNA topoisomerase in
      cell defense and response to the alkylating agent. However, the variable
      potentiation of the cytotoxic effects of melphalan achieved in different cell
      systems suggests that factors other than the level of expression of the
      modulation target are responsible of such potentiation.

PMID- 8862731
TI  - Antineoplastic activities of 2,3,4-chloro-substituted beta
      alkylaminopropiophenone derivatives in CF1 mice and in murine and human tumor
      cells.
AB  - A series of beta-alkylaminopropiophenone derivatives were demonstrated to be
      potent antineoplastic agents. Several compounds showed activity against Ehrlich
      ascites carcinoma growth in CF1 mice by demonstrating over 70% inhibition. Most
      of these agents proved to be potent cytotoxic agents in inhibiting the growth of
      a number of murine and human cancer cell lines grown in tissue culture. Their
      ED50 values were comparable to those of the selected standard anticancer drugs,
      such as 6-MP, ara-C, hydroxyurea, 5-FU, 6-aza-UMP, etoposide, antimycin A,
      actinomycin D and cycloheximide. In the mode of action studies in Tmolt3 cells,
      beta-(3",5"-dimethyl)piperidinopropiophenone was observed to reduce DNA and RNA
      synthesis significantly at 25 microM within 60 min incubation. The site of action
      of this agent appears to involve the reduction of the activities of Tmolt3 DNA
      polymerase alpha 1 dihydrofolate reductase, PRPP-amido transferase and
      ribonucleoside reductase.

PMID- 8862732
TI  - Uptake and retention in suckling rats of 51chromium fed with human milk or infant
      formulas.
AB  - Optimum concentration of Cr for infant formulas has not been established. Such
      components as soy protein or supplemental Fe could influence absorption and
      retention. Suckling rat pups were used to evaluate the influence of three
      commercial formulas and human milk, all of which had been incubated with 51CrCl3
      for 1 h, on the uptake and retention of the added 51Cr. After fasting 3 h, the
      pups were intubated with a single dose of 25 microCi 51CrCl3 in either a cow's
      milk-based formula, an Fe-supplemented cow's milk-based formula, a soy-based
      formula, or human milk. Six hours later, 51Cr was counted in five organs, thymus,
      blood, and total urine. Absorption of 51Cr was low. At 6 h, percent 51Cr in blood
      was < 0.2% of the dose, and total 51Cr excretion in urine was < 1.8%. The uptake
      and retention of 51Cr and its concentration in any of the organs, thymus, blood,
      and urine were not influenced by different types of formula or by human milk.

PMID- 8862733
TI  - Zinc status does not affect aluminum deposition in tissues of rats.
AB  - To examine whether zinc deficiency would increase the toxicity of dietary
      aluminum, weanling, male Sprague-Dawley rats were fed purified diets containing
      either 2 or 30 mg Zn/kg diet, with or without 500 mg Al/kg diet for 28 d.
      Individually pair-fed rats were fed the 30 mg Zn/kg diet with or without added
      aluminum to control for inanition secondary to zinc deficiency. Rats fed the 2
      micrograms Zn/kg diet showed evidence of zinc deficiency, including anorexia,
      growth retardation, and depressed concentrations of zinc in tibias and livers.
      Zinc deficiency did not significantly increase the concentrations of aluminum in
      the tibias, livers, kidneys, or regions of the brain examined (cerebrum,
      cerebellum, midbrain, and hippocampus). Inclusion of aluminum in the diet did not
      alter aluminum concentrations in the various tissues. Under the conditions of
      this study, zinc deficiency did not result in greater sensitivity to dietary
      aluminum exposure.

PMID- 8862734
TI  - Protection by zinc against UVA- and UVB-induced cellular and genomic damage in
      vivo and in vitro.
AB  - For many years, zinc salts have been used both topically and orally to treat
      minor burns and abrasions as well as to enhance wound repair in man and animals.
      In this study we describe the protective effects of zinc against UV-induced
      genotoxicity in vitro and against sunburn cell formation in mouse skin in vivo.
      Cultured skin cells from neonatal mice showed a dramatic increase in the number
      of micronuclei as a result of UVA and UVB irradiation. Inclusion of zinc at 5
      micrograms/mL in the medium significantly reduced the frequency of micronuclei
      and of micronucleated cells. In hairless mice, topical application of zinc
      chloride for 5 consecutive days or a single application 2 h prior to UV exposure
      reduced the number of sunburn cells in the epidermis as did application of zinc 1
      h after exposure. Application 2 h after irradiation also tended to have a
      protective effect, although there was a large variation between animals. It is
      proposed that an influx of zinc can protect epidermal cells against some of the
      more delayed effects of UV-induced damage.

PMID- 8862735
TI  - Black tea, green tea, and tea polyphenols. Effects on trace element status in
      weanling rats.
AB  - Previous studies have shown that tea consumption can impair trace element
      metabolism, particularly iron status, and increase the risk of anemia in humans
      and animals. More recently, however, evidence has been accumulating to show that,
      in animals, consumption of green tea or its polyphenols is associated with a
      reduction of the incidence and severity of a variety of experimentally induced
      cancers. In this study we have monitored the growth, trace element status,
      including hematological parameters of weanling rats given either (1) water, (2)
      1% black tea, (3) 1% green tea, or (4) 0.2% crude green tea extract as their sole
      drinking fluid while consuming diets containing either adequate or low amounts of
      iron. With the exception of manganese, none of the trace elements studied (iron,
      copper, zinc, and manganese) or the hematological indices measured were affected
      by the type of beverage supplied, even though the polyphenol extract was shown to
      chelate metals in vitro and all the animals fed the low iron diet were shown to
      be anemic. There appeared to be an effect of black and green teas on manganese
      balance in both the first and last weeks of the study. A lower level of brain
      manganese was associated with green tea consumption, and a higher level of this
      element in the kidneys of animals fed black tea. The results demonstrate that
      both black and green teas and a green tea polyphenol extract do not represent a
      risk to animals consuming the beverages as their sole fluid intake with respect
      to iron availability, although the interactions with manganese deserve further
      study.

PMID- 8862736
TI  - Concentration of rare earth elements, As, and Th in human brain and brain tumors,
      determined by neutron activation analysis.
AB  - Toxic elements As and Th, six rare-earth elemental profiles of brain tumor
      tissues from 16 patients of astrocytomas (grade I-III), and normal human brain
      tissues of 18 male, age-matched autopsies serving as controls have been studied
      by radiochemical neutron activation analysis. P-204 [di(2-ethylhexyl) phosphate]
      extraction chromatography column was used for group separation of rare-earth
      element (REE) by one step. Compared with the normal brain tissues, the analytical
      results showed that the concentrations of Th, La, Ce, Gd, and Lu were
      significantly higher in tumor tissues (P < 0.01 or 0.001). The possible effects
      of REE on tumor cell were discussed.

PMID- 8862737
TI  - Plasma selenium levels in rheumatoid arthritis.
AB  - The plasma selenium (Se) levels were determined in patients with rheumatoid
      arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found
      to be significantly lower than those in 60 normal, healthy controls (p < 0.001).
      Similar significant differences were determined in sex-matched comparisons
      between patients and controls (p < 0.001) but there was no significant difference
      in plasma Se levels in sex-matched comparisons in both groups (p > 0.05). Our
      results suggest that Se is an important factor in RA.

PMID- 8862738
TI  - Neurological disorder and excessive accumulation of calcium in brain of
      clinically vitamin A-deficient rats.
AB  - Three groups of rats were fed two types of synthetic diets for 52 d. The -A group
      was allowed free access to a vitamin A-deficient diet and showed classical signs
      of vitamin A deficiency. The brain was the only organ in our experiment where no
      significant weight difference was present among the three groups. In the brain,
      calcium concentration was significantly higher in the -A group when compared with
      the PF (Pair-fed; allowed restricted amount of control diet) and +A groups
      (allowed free access to control diet). In the tibia, calcium and magnesium
      concentrations were significantly lower in the -A group when compared with other
      two groups. Excessive accumulation of calcium in brain and apparently similar
      unbalance in bone mineral concentration were observed in central nervous system
      (CNS) degenerative diseases. Our results suggest that abnormal metabolism of
      calcium and magnesium in some tissues and excessive accumulation of calcium in
      brain may be responsible for the development of neurological disorders in vitamin
      A-deficient rats.

PMID- 8862740
TI  - Induction and characterization of metallothionein in different organs of Ostrea
      edulis L.
AB  - In this study, the induction of metallothionein (MT) in one species of oyster
      Ostrea edulis exposed to copper (Cu) and zinc (Zn) was examined. The quantity of
      total protein (mg protein/mg dry wt) in each sample and the measurement of MT
      were determined by the Lowry and silver (Ag)-saturation methods. Our results show
      that the gonads are the organs producing the greatest quantity of MT in the
      controls and in the groups induced by Cu and Zn, followed by the mantle, gut, and
      by muscle and plasma. Competition by Zn with respect to Cu for the production of
      MT has been established.

PMID- 8862739
TI  - Selenium-vitamin E supplementation in infertile men. Effects on semen parameters
      and micronutrient levels and distribution.
AB  - In order to verify the hypothesis that selenium (Se) and vitamin E (Vit E) could
      improve male fertility, nine oligoasthenoteratozoospermic men were supplemented
      for a period of 6 mo with Se and Vit E. Compared to the baseline period
      (presupplementation) of 4 mo, statistically significant increases were observed
      for Se and Vit E levels, sperm motility, percent live, and percent normal
      spermatozoa. These improvements are likely to be "supplementation-dependent,"
      since all of the parameters returned to baseline values during the posttreatment
      period. None of the couples reported a pregnancy during the study. The HPLC
      analysis conducted on the serum of one of the patients showed the existence of at
      least six different Se-containing peaks, whose Se content was affected by
      supplementation. The mechanism(s) involved in these improvements of semen
      parameters is presently under investigation.

PMID- 8862741
TI  - Potassium changes in trained subjects after potassium loading and during
      restriction of muscular activity and chronic hyperhydration.
AB  - The objective of this investigation was to determine whether urinary and plasma
      potassium changes developed during prolonged hypokinesia (HK) (decreased number
      of km/d) in endurance-trained subjects could be minimized or reversed with a
      daily intake of fluid and salt supplementation (FSS). The studies were performed
      on 30 endurance-trained male volunteers aged 23-26 yr with an average peak oxygen
      uptake of 65 mL/kg min during 364 d of HK. All volunteers were on an average of
      13.8 km/d prior to their exposure to HK. All volunteers were randomly divided
      into three groups: 10 volunteers were placed continuously under an average of
      14.0 km/d (control subjects), 10 volunteers were subjected continuously to an
      average of 2.7 km/d (unsupplemented hypokinetic subjects), and 10 volunteers were
      submitted continuously to an average of 2.7 km/d, and consumed daily an
      additional amount of 0.1 g sodium chloride (NaCl)/kg body wt and 30 mL water/kg
      body wt (supplemented hypokinetic subjects). During the prehypokinetic period of
      60 d and during the hypokinetic period of 364 d, potassium loading tests were
      performed with 1.5-1.7 mEq potassium chloride/kg body wt, and potassium, sodium,
      and chloride excretion in urine and potassium, sodium, and chloride in plasma
      were determined. In the unsupplemented hypokinetic volunteers, urinary excretion
      of electrolytes and concentrations of electrolytes in plasma increased
      significantly as compared to the control and supplemented hypokinetic groups of
      volunteers. It was concluded that daily intake of fluid and salt supplementation
      had a favorable effect on regulation of urinary and plasma potassium changes in
      trained subjects during prolonged HK.

PMID- 8862742
TI  - Discrepancy between cytotoxicity, platinum accumulation, and DNA platination in
      MCF-7 breast cancer cells treated with diaqua (1,2-diphenylethylenediamine)
      platinum (II) sulfates and cisplatin.
AB  - Cisplatin (cis), raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]
      platinum(II) sulfate (r-4F-PtSO4), meso-diaqua[1,2-bis(4
      fluorophenyl)ethylenediamine]platinum(II) sulfate (m-4F-PtSO4), and meso
      diaqua[1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] platinum(II) sulfate
      (m-2,6Cl2-4OH-PtSO4) were compared with regard to their growth inhibitory effect
      on MCF-7 breast cancer cells. At concentrations of 5 microM, cis, r-4F-PtSO4, and
      m-4F-PtSO4 were essentially equiactive, whereas m-2,6Cl2-4OH-PtSO4 was
      ineffective. Platinum measurements by neutron activation analysis showed that a
      24-h treatment of the MCF-7 cells with r-4F-PtSO4 and m-4F-PtSO4 caused a 22.3-
      and 10.3-fold accumulation, respectively, whereas the accumulation factors for
      cis (2.55) and m-2,6Cl2-4OH-PtSO4 (1.83) were very low. The comparison of DNA
      associated platinum revealed a similar tendency. After 24 h of drug exposure, the
      base pair/ platinum ratios were: 2.1.10(4) for r-4F-PtSO4, 3.7.10(4) for m-4F
      PtSO4, 6.1.10(4) for cisplatin, and 8.1. 10(4) for m-2,6Cl2-4OH-PtSO4. Thus, the
      grade of cytotoxicity was correlated neither with the extent of cellular platinum
      enrichment nor with the degree of genomic DNA platination.

PMID- 8862743
TI  - Plasma and erythrocyte manganese concentrations. Influence of age and acute
      myocardial infarction.
AB  - This study was carried out to assess manganese (Mn) status after an acute episode
      of myocardial infarction. Plasma and erythrocyte Mn concentrations were measured
      from admission to hospital to day 15 postadmission in 21 patients suffering from
      acute myocardial infarction and in three control groups. The determination of Mn
      in these biological fluids was performed by electrothermal atomic absorption
      spectrometry. Plasma Mn was higher (p < 0.01) and erythrocyte Mn was similar in
      the acute myocardial infarction group compared to healthy age-matched control
      group. Plasma and erythrocyte Mn remained unchanged during the 2 wk after acute
      myocardial infarction and were not correlated to enzyme activities. A decrease of
      erythrocyte Mn with age, expressed in nmol/L, was noted (p < 0.02). These results
      suggest that plasma and erythrocyte Mn do not provide an indication of myocardial
      damage. Nonetheless, Mn status in elderly merits further attention.

PMID- 8862744
TI  - Effect of magnesium supplementation and training on magnesium tissue distribution
      in rats.
AB  - The aim of this work is to study the effect of training and Mg supplementation on
      body pools of Mg and on Mg tissue distribution. Forty male Wistar rats were
      divided into four groups (n = 10): control group (C); trained group (T); Mg
      supplemented group (+Mg); and trained and Mg-supplemented group (+MgT). The Mg
      supplement (1000 ppm of Mg) was given in the drinking water for 21 d. The
      training consisted of swimming during 60% of maximal swimming time obtained in
      the first session to exhaustion, during 3 wk (5 d a week). The variables measured
      were: erythrocytes (RBC), hemoglobin (Hb), hematocrit (Hto), total proteins (TP),
      and Mg in serum, RBC, liver, muscle, bone, and kidney. There was less Mg in
      liver, muscle, and erythrocyte in trained animals than in control or supplemented
      animals (T vs C, +MgT vs C and +MgT vs +Mg) (p < 0.01). Trained animals (T and
      +MgT) showed higher Mg kidney rates than the untrained ones (p < 0.01). There was
      less bone Mg in control (C) and in supplemented and trained (+MgT) groups than in
      trained (T) and in supplemented (+Mg) animals (p < 0.01). Serum Mg showed a
      decreasing concentration profile in the following order: +Mg, +MgT, T, C (p <
      0.01). We conclude that Mg supplementation improves bone and serum Mg levels, but
      this does not affect Mg status in soft tissues. Maintained exercise leads to a
      diminution of Mg in the aforementioned soft tissues that is not noticeable in
      serum, probably provoked by an increase of renal excretion.

PMID- 8862745
TI  - Calcium, magnesium, and phosphorus content of hair from two populations of rhesus
      monkeys.
AB  - The use of hair for the assessment of human mineral nutritional status is
      controversial, yet has potential because of the ease of collection and storage,
      and the high concentration of minerals in hair. This study generated baseline
      values for hair macromineral content in the most commonly used primate model for
      human nutrition and disease, the rhesus monkey. Hair digests from monkeys in
      Maryland (n = 98) and Puerto Rico (n = 208) were analyzed by inductively coupled
      plasma atomic emission spectrometry (ICP-AES). Significant differences existed
      between the two populations for hair calcium (Ca), magnesium (Mg), and phosphorus
      (P) (P < 0.01, P < 0.001, P < 0.02). Male hair had higher concentrations of Mg in
      specimens from the Puerto Rican population (P < 0.001), whereas hair phosphorus
      was higher in female hair (P < 0.02). There were no significant differences
      attributable to pregnancy status. Differences in hair content attributable to
      categorical age were found for Ca and Mg (P < 0.001, P < 0.01). Significant
      location differences paralleled dietary differences. These values therefore can
      be considered reference ranges for hair Ca, Mg, and P for free-ranging and caged
      rhesus monkeys.

PMID- 8862746
TI  - Copper, iron, manganese, and zinc content of hair from two populations of rhesus
      monkeys.
AB  - The concentrations of the elements copper (Cu), iron (Fe), manganese (Mn), and
      zinc (Zn) in hair of caged (in Maryland) and free-ranging (in Puerto Rico) rhesus
      monkey populations were determined. Significant chronological age-related
      decreases were evident for the trace elements Mn and Zn in both populations (P <
      or = 0.01) and for Cu and Fe in free-ranging monkeys (P < or = 0.005). The only
      overall gender difference was higher hair Mn concentration in free-ranging males
      than in females (P < 0.03). There were no significant differences in hair Cu, Fe,
      or Mn related to pregnancy status. Hair Zn was lower in samples from pregnant
      than from nonpregnant monkeys from the caged monkeys (P < or = 0.05), but did not
      differ in the free-ranging monkeys. Comparison of the two populations revealed
      that hair Zn levels were significantly higher in caged vs free-ranging animals (P
      < 0.001). We attribute this higher hair Zn in the caged monkeys to contact and
      ingestion of Zn from their galvanized enclosures. Hair iron levels were
      significantly higher (P < 0.001) in free-ranging monkeys, possibly as a result of
      Fe-rich soil ingestion from their environment. These data support continued
      investigation of the use of hair as an indicator of the exposure of large groups
      or populations to potentially high levels of specific minerals, and the use of
      nonhuman primates as models for the study of trace element deficiency and/or
      toxicity in humans.

PMID- 8862747
TI  - Effect of vanadium compounds on acid phosphatase activity.
AB  - The direct effect of different vanadium compounds on acid phosphatase (ACP)
      activity was investigated. Vanadate and vanadyl but not pervanadate inhibited the
      wheat germ ACP activity. These vanadium derivatives did not alter the fibroblast
      Swiss 3T3 soluble fraction ACP activity. Using inhibitors of tyrosine
      phosphatases (PTPases), the wheat germ ACP was partially characterized as a
      PTPase. This study suggests that the inhibitory ability of different vanadium
      derivatives to modulate ACP activity seems to depend on the geometry around the
      vanadium atom more than on the oxidation state. Our results indicate a
      correlation between the PTPase activity and the sensitivity to vanadate and
      vanadyl cation.

PMID- 8862748
TI  - Aluminum chelation by 3-hydroxypyridin-4-ones in the rat demonstrated by
      microdialysis.
AB  - The ability and site of the metal-chelating 3-hydroxypyridin-4-ones (HPs) to
      mobilize aluminum (Al) was assessed in Al-loaded rats using microdialysis. Four
      HPs with greatly varying lipophilicity were studied. One week after Al loading,
      microdialysis probes were implanted in the liver, a jugular vein, and the frontal
      cortex. An HP was given iv followed by continuous microdialysis for 5 h. Al
      concentrations in dialysates from the liver increased rapidly and were
      consistently greater than from blood, suggesting that liver was a primary site of
      Al chelation. Brain dialysate Al concentrations remained low, suggesting little
      Al chelation in the brain and little distribution of the Al HP complex into the
      brain. Al concentrations were determined in the main organs/tissues of a separate
      group of Al-loaded rats, and the percentage of the total Al body burden in each
      organ/tissue was calculated. The skeletal system and liver had 57 and 28% of the
      Al body burden, consistent with the liver as a primary site of Al chelation. The
      HPs chelate extravascular Al and have been shown by others to be orally active.
      They warrant further investigation as Al chelators.

PMID- 8862749
TI  - Urinary cadmium levels during pregnancy and postpartum. A longitudinal study.
AB  - It is well established that pregnancy induces physiological, metabolical and
      hormonal changes. As a consequence, trace metal metabolism can be affected. The
      aim of the present study was to assess the urinary cadmium levels in women during
      gestation and postpartum. The survey was conducted in a group of
      nonoccupationally cadmium-exposed women from Southern Catalonia (NE, Spain).
      Urine samples were obtained before pregnancy, during the 6th, 10th, 26th, and
      30th wk of gestation, as well as during the 5th and 24th wk after delivery.
      Urinary cadmium levels were determined by graphite furnace atomic absorption
      spectrophotometry. The concentrations of zinc and copper in plasma were also
      measured. Moreover, to assess the effect of the diet during pregnancy, dietary
      ingestions of zinc, iron, and calcium were also determined. A significant
      decrease of plasma zinc levels could be observed during the last two trimesters
      of pregnancy, while plasma copper concentrations significantly increased during
      the same period. Urinary cadmium concentrations ranged from 0.05 to 3.79
      micrograms/g creatinine (geometric mean 0.49 +/- 2.26 micrograms/g creatinine).
      No significant changes in urinary cadmium concentrations during pregnancy and
      postpartum could be observed.

PMID- 8862750
TI  - Effect of zinc on aminopeptidase N activity and L-threonine transport in rabbit
      jejunum.
AB  - Zinc is a nutritionally essential trace element required for many biological
      functions to be successfully carried out. The aim of the present work was to
      study the influence of zinc on the intestinal absorption of L-threonine and on
      the aminopeptidase N activity in rabbit jejunum, after in vitro addition and/or
      oral administration of ZnCl2 in drinking water. Results obtained show that zinc
      decreases L-threonine absorption in the jejunal tissue. This effect would appear
      to be owing to an action mainly located in active amino acid transport, because
      zinc does not seem to modify the amino acid diffusion across the intestinal
      epithelium, of the mucosal border of the intestinal epithelium. Zinc has also
      been shown to inhibit the (Na(+)-K+)-ATPase activity of the enterocyte, which
      might explain the inhibition of the L-threonine Na(+)-dependent transport.
      Nevertheless, a direct action of the zinc on carriers of active transport cannot
      be rejected. However, zinc did not significantly modify the aminopeptidase N
      activity in rabbit jejunum.

PMID- 8862751
TI  - Subcellular distribution of protein kinase C (pKC) in erythrocytes and
      concentration of D-myo-inositol-1,4,5-trisphosphate (IP3) in platelets and
      monocytes of force-fed zinc-deficient rats.
AB  - The purpose of the present study was to investigate whether alimentary zinc (Zn)
      deficiency affects the activities of the Zn metalloenzymes protein kinase C (pKC)
      and the phosphatidylinositol-specific phospholipase C (PLC) in force-fed Zn
      deficient rats. The in vivo activity of pKC was determined by measuring the
      subcellular distribution of the enzyme between the cytosolic and the particulate
      fraction of erythrocytes, whereas the activity of PLC was measured indirectly
      through the concentration of its metabolite inositol-1,4, 5-trisphosphate (IP3)
      in platelets and monocytes. For this purpose, 24 male Sprague-Dawley rats with an
      average live mass of 126 g were divided into 2 groups of 12 animals each. The Zn
      deficient and the control rats received a semisynthetic casein diet with a Zn
      content of 1.2 and 24.1 ppm, respectively. All animals were fed the same amount
      of the diet (10.8 g dry matter [DM]/d and rat) four times daily by gastric tube.
      After 12 d, the depleted rats were in a state of severe Zn deficiency, as
      demonstrated by a 70% lower Zn concentration and a 66% reduction in the serum
      activity of alkaline phosphatase. The radio-immunologically determined
      concentration of IP3 was reduced by a significant 55% in the platelets of the Zn
      deficient rats (8.4 pmol IP3/ 5 x 10(8)) as compared with the control rats (18.8
      pmol IP3/5 x 10(8)), whereas the IP3 concentration in the monocytes was not
      affected by the alimentary Zn supply (1.4 vs 1.2 pmol IP3/10(6)), nor was there
      any difference between the Zn-deficient and the control rats with regard to the
      radioenzymatically determined specific activity of pKC, either in the cytosolic
      fraction (32.7 vs 32.5 pmol P/min/mg protein) or in the particulate fraction
      (38.1 vs 36.5 pmol P/min/mg protein) of the erythrocytes.

PMID- 8862752
TI  - Magnesium and iron contents of leukemic lymphocytes in acute leukemias and
      hemolytic anemia.
AB  - In this study, magnesium and iron concentrations were measured in lymphocytes
      from patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia
      (AML), and hemolytic anemia (HA) before and after chemotherapy treatment. The
      results were compared with those of control subjects. Magnesium concentrations
      were significantly lower in the patient groups, compared with control values.
      However, no significant differences, except in the HA group, were found among
      magnesium concentration of the patient groups themselves. Iron level values were
      at physiological range in all groups. Similarly, no statistically significant
      differences were found between lymphocyte magnesium concentrations before and
      after chemotherapy treatment in the patient groups. Fe+3 values were higher in
      the ALL and HA groups with respect to the group before chemotherapy.

PMID- 8862753
TI  - Trace elements in scalp hair of professional drivers and university teachers in
      Hong Kong.
AB  - Hair samples of 23 male professional drivers and 20 male university teachers in
      Hong Kong were collected, and the concentrations of Al, Sb, As, Ca, Cu, Fe, Pb,
      Mg, Mn, Hg, K, Sr, S, V, and Zn were measured. Both of the target groups fell
      within the same age group of 35-45. The washing method of using detergent and
      powder was found to be comparable to that of using ether. Difference in the mean
      concentration of each detected element in the two groups was tested by the
      Student's t-test and the Wilcoxon rank-sums test. Hair concentrations of Al, Sb,
      Pb, Mg, Mn, and K in the "Driver Group" were significantly (p < 0.05) higher than
      those in the "Teacher Group." On the other hand, As and Hg were found to have a
      higher concentration in hair of teachers. Interpretation of the findings in terms
      of the environmental factor and the metabolic rate was attempted.

PMID- 8862754
TI  - Biokinetics of lead in various organs of rats using radiotracer technique.
AB  - Uptake, distribution, and elimination of lead in various organs of rats have been
      studied using a radiotracer technique. The elimination data for various organs,
      except whole blood, is fitted to a double-exponential function using a computer
      program. The biological half-lives along with the percent elimination of lead by
      two different decay modes in testis, epididymis, prostate, and seminal vesicles
      are being reported together with that in liver, kidney, blood, and whole body. It
      is evident from this study that the elimination of lead is limited for all the
      organs and permits lead accumulation in the bone, where it is stored and becomes
      almost unavailable for elimination. Lead levels in blood, testis, and femur of
      lead acetate-fed rats measured using atomic absorption spectroscopy have been
      correlated to the uptake of 210Pb in various organs.

PMID- 8862755
TI  - Copper absorption, endogenous excretion, and distribution in Sprague-Dawley and
      lean (Fa/Fa) Zucker rats.
AB  - We previously observed a rapid reduction in plasma ceruloplasmin activity in lean
      Zucker (Fa/Fa) rats fed a marginal copper (Cu)-deficient diet compared to
      similarly fed obese Zucker (fa/fa) and lean Sprague-Dawley rats. In an effort to
      understand the mechanisms underlying this response, we utilized the isotope
      dilution method to investigate the absorption and excretion of Cu in lean Zucker
      rats fed control and marginal Cu diet. Sprague-Dawley (SD) and homozygous lean
      Zucker rats were fed either a Cu-adequate (Cont; 7.5 micrograms Cu/g diet) or a
      low Cu (Low; 1.1 micrograms Cu/g diet) casein-based diet for 23 d. Two weeks
      following initiation of the dietary treatment, each rat was injected
      intramuscularly (im) with 11.2 microCi of 67Cu. Urine and feces were collected
      daily. On the 9th d following isotope injection, rats were killed and tissues
      collected. Significant dietary effects were observed in the relative absorption
      and endogenous fecal excretion of 67Cu. The tissue distributions of nonisotopic
      Cu and 67Cu activity were also different between dietary treatments. Tissues from
      rats fed the low-Cu diet typically had high concentrations of 67Cu and low
      concentrations of nonisotopic Cu compared to controls. An increase in relative
      67Cu absorption was evident for rats fed the low-Cu diet (57.2 and 39.3%, for SD
      Low, Zucker Low, respectively, and 17.9, and 28.5% SD Cont and Zucker Cont,
      respectively). Rats fed the low-Cu diet also had reductions in endogenous fecal
      excretion of 67Cu compared to their respective controls. Although strain effects
      were not evident for either percent Cu absorption or endogenous fecal Cu
      excretion, the relative adaptive changes appeared more marked for the Sprague
      Dawley rats compared to the lean Zucker rats.

PMID- 8862756
TI  - Toxicity to alveolar macrophages in rats following parenteral injection of
      mercuric chloride.
AB  - Alveolar macrophages collected by pulmonary lavage from male Fisher-344 rats at
      intervals (24-72 h) after HgCl2 injection (1-5 mg/kg, s.c.) were analyzed by
      several techniques. Within 24-72 h, the macrophages showed morphological signs of
      activation (hypertrophy and ruffled plasma membrane). Lipid peroxidation
      (increased malondialdehyde concentration) was not detected until 48 h. Dose- and
      time-related effects of HgCl2 on malondialdehyde concentration and mercury
      content of alveolar macrophages were observed 24-72 h postinjection. Diminished
      cell viability occurred only at 72 h after the highest dosage of HgCl2. This
      study demonstrates that the alveolar macrophage was a cellular target for mercury
      toxicity following parenteral exposure to HgCl2.

PMID- 8862757
TI  - Determination of selenium in the human brain by graphite furnace atomic
      absorption spectrometry.
AB  - For the investigation of neurological disorders, a development of simple and
      accessible methods for determining selenium in human brain samples is required.
      We devised a method of determining selenium using graphite furnace atomic
      absorption spectrometry (GFAAS). An electrodeless discharge lamp provided the
      sufficient sensitivity to determine brain selenium. The matrix interferences were
      avoided by using high temperature, a prolonged pyrolysis step, and a palladium
      matrix modifier. The technique of standard addition was used to evaluate the
      sample concentrations. The accuracy of the method was confirmed by a bovine liver
      reference material. The detection limit of selenium was 0.04 ng. The determined
      selenium concentrations of human brain cortex and white matter were higher than
      those of putamen (115-155 and 206-222 ng/g wet wt, respectively). These GFAAS
      values agreed with those obtained by fluorometric analysis (r = 0.91, n = 10).
      Moreover, the GFAAS values were compatible to those reported by other researchers
      (99-274 ng/g wet wt), in which selenium concentrations in putamen also tended to
      be higher than the other two regions. We conclude that GFAAS is useful for
      selenium analysis in brain samples.

PMID- 8862758
TI  - Age-related change of mineral content in the human thoracic aorta and in the
      human cerebral artery.
AB  - The relative contents (RCs) of mineral elements in aortae and cerebral arteries
      from 23 subjects, with ages ranging between 45 and 99 yr, were analyzed by
      inductively coupled plasma atomic emission spectrometry. The RCs of calcium,
      phosphorus, and magnesium in the aortae increased markedly after the age of 70.
      While the RC of sulfur in aortae decreased gradually after that age. It was found
      that accumulation of calcium and phosphorus occurred primarily in the tunica
      media of aorta, and secondarily in the tunica intima. Furthermore, the RCs of
      calcium, phosphorus, and magnesium in cerebral arteries increased markedly after
      the age of 70, whereas the RC of sulfur in cerebral arteries decreased after age
      70. It was found that accumulation of calcium and phosphorus in the cerebral
      arteries were 30 and 60%, respectively, lower than those in the aortae with ages
      ranging between 45 and 99 yr.

PMID- 8862759
TI  - Lipid peroxidation in liver of rats administrated with methyl mercuric chloride.
AB  - Parenteral administration of methyl mercuric chloride (MMC, CH3HgCl) to rats
      enhanced lipid peroxidation in liver of rats, as measured by the thiobarbituric
      acid reaction for malondialdehyde (MDA) in fresh tissue homogenates. After sc
      injection of CH3HgCl (5 mg/kg body wt), MDA concentration in liver became
      significantly increased at 24 h and further increased at 48 h. Dose-response
      studies were carried out with male albino rats of the Fisher-344 strain (body wt
      170-280 g) injected with 3 or 5 mg Hg/kg as CH3HgCl and sacrificed after 24 h. In
      time-response studies, animals were administered 5 mg Hg/kg as CH3HgCl and
      sacrificed after 24 and 48 h. Studies in the authors' laboratory have shown that
      (1) mercury is accumulated in liver; (2) concentration of MDA is increased in
      liver of CH3HgCl-treated rats; (3) severity of hepatotoxicity is generally
      proportional to the elevation of MDA concentration, based upon the dose-effect
      relationships observed after administration of CH3HgCl to rats. The results of
      this study implicate that the lipid peroxidation is one of the molecular
      mechanisms for cell injury in acute CH3HgCl poisoning.

PMID- 8862760
TI  - Effects of aluminum chloride on normal and uremic adult male rats. Tissue
      distribution, brain choline acetyltransferase activity, and some biological
      variables.
AB  - Normal and uremic adult male rats were given a daily ip injection of 20 mg Al (Al
      chloride)/kg for 14 d. The results indicate that Al induces a significant
      decrease in food ingestion, weight gain, and total protein concentration in the
      plasma. Compared with control animals, very high increases in Al levels were
      found in plasma and hepatic homogenates (about 36 and 19 times, respectively). In
      the brain homogenates, the Al increases were lower (about 23%). The brain
      cholineacetyltransferase activity was reduced: 10.6 and 14.9% in normal and
      uremic rats, respectively. The nephrectomy and the food restriction did not
      affect the total protein concentrations in plasma and the cerebral
      cholineacetyltransferase activity. Both were only found to be reduced in the rats
      treated by Al chloride.

PMID- 8862761
TI  - Effect of age and dietary protein level on tissue mineral levels in female rats.
AB  - Mineral (phosphorus, sulfur, potassium, calcium, magnesium, iron, zinc, copper,
      and manganese) concentrations were measured in plasma, and several tissues from
      female Wistar rats (young: 3-wk-old; mature: 6-mo-old) were fed on a dietary
      regimen designed to study the combined or singular effects of age and dietary
      protein on mineral status. Three diets, respectively, contained 5, 15, and 20% of
      bovine milk casein. Nephrocalcinosis chemically diagnosed by increased calcium
      and phosphorus in kidney was prevented in rats fed a 5% protein diet. Renal
      calcium and phosphorus were more accumulated in young rats than mature rats. A 5%
      protein diet decreased hemoglobin and blood iron. The hepatic and splenic iron
      was increased by a 5% protein diet in mature rats but was not altered in young
      rats. Mature rats had higher iron in brain, lung, heart, liver, spleen, kidney,
      muscle, and tibia than young rats. A 5% protein diet decreased zinc in plasma and
      liver. Zinc in tibia was increased with dietary protein level in young rats but
      was not changed in mature rats A 5% protein diet decreased copper concentration
      in plasma of young rats but not in mature rats. Mature rats had higher copper in
      plasma, blood, brain, lung, heart, liver, spleen, and kidney than young rats.
      With age, manganese concentration was increased in brain but decreased in lung,
      heart, liver, kidney, and muscle. These results suggest that the response to
      dietary protein regarding mineral status varies with age.

PMID- 8862762
TI  - Urinary and plasma calcium changes in endurance trained volunteers during
      exposure to acute and rigorous bed rest conditions.
AB  - The purpose of the present study was to evaluate the effect of acute (abrupt
      restriction of muscular activity) and rigorous bed-rest conditions on urinary and
      plasma calcium changes in endurance trained volunteers. The studies were
      performed on 30 long distance runners ages 23-25 who had a peak oxygen uptake of
      66.0 mL/min/kg and had run 14.0 km/d on the average prior to their participation
      in the study. The volunteers were divided into three groups: The volunteers in
      the first group were under normal ambulatory conditions (control subjects), the
      second group was subjected to an acute bed-rest regime (acute bed-rested
      subjects), and the third group was submitted to a rigorous bed-rest regime
      (rigorous bed-rested subjects). The second and third groups of volunteers were
      kept under a rigorous bed rest regime for 7 d. During the pre-bed-rest period and
      during the actual bed-rest periods (acute and rigorous bed-rest periods), urinary
      excretion of calcium and plasma calcium and parathyroid hormone (PTH)
      concentrations were determined. During the 1st d of acute and rigorous bed-rest
      periods, urinary excretion and plasma concentration of calcium increased
      significantly (P < or = 0.05), while plasma parathyroid hormone content decreased
      significantly (P < or = 0.05). On the 3rd d of the experimental period, urinary
      excretion and plasma calcium concentration decreased somewhat, during the 7th d,
      calcium in urine and plasma increased further, while parathyroid hormone content
      in plasma increased somewhat on the 3rd d and decreased again on the 7th d of the
      experimental period. The changes were more pronounced in the volunteers who were
      subjected to acute bed-rest conditions than in the volunteers who were submitted
      to rigorous bed-rest conditions. It was concluded that exposure to acute bed-rest
      conditions induces significantly greater urinary and serum calcium changes than
      rigorous bed-rest conditions in endurance trained volunteers.

PMID- 8862763
TI  - The influence of aging on renal response to cadmium in Syrian hamsters.
AB  - To determine the renal effects of cadmium (Cd) in older animals, we administered
      subcutaneously a single dose of cadmium, 3.0 mg/kg/BW, to Syrian hamsters aged 16
      wk ("young") and 60 wk ("old"). Marked morphologic changes in the kidney and
      renal dysfunction were observed, especially in the older animals. The
      concentration of MDA in the renal cortex was significantly increased only in
      young hamsters treated with cadmium. Concentrations of glutathione (GSH) in the
      renal cortex were increased in the old hamsters on d 6. Increased levels of renal
      MDA after cadmium treatment may induce the production of GSH in the kidney thus
      preventing renal damage. Aging can increase the susceptibility to the renal
      effects of cadmium.

PMID- 8862765
TI  - Temporal and spatial expression of tissue inhibitors of metalloproteinases during
      the natural ovulatory cycle of the mouse.
AB  - The role of tissue inhibitors of metalloproteinases (TIMPs) in ovarian function
      has primarily been documented by studies that utilize hormone-primed animals. In
      this study, our objectives were to elucidate the spatiotemporal expression of
      individual TIMP genes during the natural ovulatory cycle, and to correlate these
      with specific biological events. Two models of spontaneous ovulation used were
      the murine estrous cycle and the first ovulation postpartum. Ovaries were
      collected from mice at diestrus, estrus, and metestrus, or at early and late
      proestrus, and from pregnant females on Days 17 and 18 of gestation (D17, D18)
      and within 24 or 48 h postpartum (PP1, PP2). We observed that TIMP-1 mRNA was
      elevated at early proestrus and D18 and was maximal at late proestrus and PP1.
      The TIMP-3 pattern was distinct from that of TIMP-1, maximal expression occurring
      at early proestrus and D17 and D18. In both models, TIMP-2 mRNA remained constant
      and at very low levels throughout ovulation. In situ hybridization localized TIMP
      1 mRNA to the corpus luteum at D18 and PP1, and to oocytes at specific stages of
      follicular development. Expression of TIMP-1 in granulosa and thecal cells was
      not observed at any stage. Demonstrating a distinct distribution, TIMP-3 mRNA was
      localized to oocytes, thecal and granulosa cells of small and large follicles,
      and corpora lutea only at D17. These data suggest specific hormonal regulation of
      individual TIMP gene expression in the ovary associated with distinct
      physiological functions. We propose that in the natural ovulatory process, TIMP-1
      is probably a factor that regulates corpus luteum regression while TIMP-3 is
      important in maintaining the structural integrity of the corpus luteum.

PMID- 8862764
TI  - Presence of urokinase plasminogen activator and plasminogen activator inhibitor-1
      messenger ribonucleic acids in rat endometrium during decidualization in vivo.
AB  - Rat endometrial stromal cells undergoing decidualization in vitro secrete
      urokinase-type plasminogen activator (uPA), and this secretion is regulated by
      prostaglandin E2. The present study was undertaken to determine whether uPA and
      plasminogen activator inhibitor-1 (PAI-1) mRNAs are expressed in vivo in the
      decidua of pregnant rats and in the deciduoma of "pseudopregnant" rats. Total RNA
      was prepared from nondecidualized and decidualized endometrial tissues at various
      stages of early pregnancy and examined by Northern blot analysis using specific
      cDNA probes for rat uPA and PAI-1. There was little uPA mRNA in the endometrium
      during the first 5 days of pregnancy (Day 1 = the presence of sperm in the
      vagina). A high level of uPA mRNA was detected on Day 7, and it declined
      thereafter. There was a gradual increase in PAI-1 mRNA in the decidua from Day 7
      of pregnancy, reaching a peak level on Day 15 when the decidua was transformed
      into the maternal placenta. (RNA was not analyzed beyond Day 15 of pregnancy in
      this study.) In situ hybridization studies verified that uPA mRNA was present in
      the decidua adjacent to the implanting embryo on Day 7. Plasminogen activator
      inhibitor-1 mRNA was scattered in the decidualized endometrium, but greater
      amounts of PAI-1 mRNA were found in the fetal tissue on Day 10 of pregnancy.
      Northern blot analysis of RNA from the deciduoma produced in ovariectomized,
      steroid-treated rats by intrauterine injection of oil demonstrated a similar
      temporal pattern of expression of uPA mRNA; i.e., the level of uPA mRNA was
      highest on Day 7 and decreased thereafter. The level of PAI-1 mRNA in deciduoma
      was not detectable by Northern blot technique during the first 10 days of
      pseudopregnancy. These findings confirm that uPA mRNA is present in vivo in rat
      decidual cells, independent of the presence of a conceptus. By contrast, the
      level of PAI-1 mRNA in the uterus is probably influenced by the presence of the
      conceptus.

PMID- 8862766
TI  - Testis of prepubertal rhesus monkeys receives a dual catecholaminergic input
      provided by the extrinsic innervation and an intragonadal source of
      catecholamines.
AB  - The mammalian testis is innervated by extrinsic catecholaminergic nerves and
      responds to catecholamines with steroid secretion. Although the primate testis
      has also been shown to be innervated, potential differences in the density of
      this innervation between immature and sexually developed individuals have not
      been described. A recent study demonstrated that the primate ovary contains a
      network of neuron-like cells and that some of these cells are catecholaminergic.
      It is thus possible that the male gonad is also endowed with a similar
      intragonadal source of catecholamines. The present study addresses these two
      issues. Catecholaminergic nerves were identified as such by their content of
      immunoreactive tyrosine hydroxylase (TH; the rate-limiting step in catecholamine
      biosynthesis), and in some cases by glyoxylic acid histochemistry. Fibers
      containing TH were abundant in testes from juvenile animals (1-2 yr of postnatal
      life), but the density of this innervation was not maintained in adult animals,
      whose testis showed only a few TH-positive fibers scattered in the interstitial
      tissue. Testicular norepinephrine (NE) concentration was much lower in adult than
      in juvenile animals, suggesting that the marked increase in testicular weight
      that occurs with the attainment of sexual maturity is not accompanied by
      corresponding changes in NE content. At the ultrastructural level, testicular
      nerve fibers contained pleiomorphic, dense-core and clear vesicles, suggesting
      the presence of catecholamines and other neurotransmitters. In addition to this
      extrinsic catecholaminergic innervation, prepubertal testes, but not adult
      gonads, contained an intrinsic population of TH-immunopositive neuron-like
      elements, identified as cells by confocal scanning laser microscopy. To determine
      whether the prepubertal monkey testis indeed expresses the TH gene, testicular
      RNA was subjected to reverse transcriptase polymerase chain reaction to amplify
      the 5' end of TH mRNA, which encodes the regulatory domain of the enzyme. The
      cDNA that was obtained predicts an amino acid sequence similar, but not
      identical, to that encoded by the alternatively spliced type 1 TH mRNA form
      present in the adrenal gland. These results indicate 1) that the primate testis
      receives a dual catecholaminergic input, one provided by the extrinsic
      innervation and the other by neuron-like cells located within the gonad itself,
      and 2) that the influence exerted by both sources on testicular function may be
      more prominent during the prepubertal period than in adulthood. The presence in
      the testis of a TH mRNA variant encoding amino acid substitutions in its 5' end
      suggests that regulation of testicular TH enzyme activity may include a gonad
      specific component.

PMID- 8862767
TI  - Maintenance of decidual cell reaction by androgens in the mouse.
AB  - In the mouse, estrogen and progesterone are required to prime the uterus for
      decidual cell reaction (DCR) in response to an intraluminal stimulus and, once
      DCR is induced, progesterone is required to maintain DCR. However, some evidence
      indicates that certain nonprogestational steroid hormones may also be involved in
      regulating DCR. The present study determined whether androgen plays any role in
      DCR. Adult CD1 mice were ovariectomized and treated with a regimen of estradiol
      and progesterone to prime the uterus for DCR and to maintain DCR. Sesame oil was
      injected into the uterine lumen to induce DCR on Day 5 of the treatment. DCR was
      determined by deciduomal weight-the difference between the wet weights of oil
      injected and noninjected uterine horns. Testosterone, given at 1 mg/day during
      Days 3-5, could not replace progesterone in priming the uterus for DCR. However,
      the same dose of testosterone given during Days 6-8 maintained DCR. Alkaline
      phosphatase activity, a bio-marker for DCR, was present in the deciduoma
      maintained by either progesterone or testosterone, although the distribution of
      this enzyme activity was more intense in the antimesometrial pole in progesterone
      maintained deciduoma. A nonaromatizable androgen, 5 alpha-dihydrotestosterone
      (DHT), was also effective in maintaining DCR, and this action of DHT was blocked
      by an androgen receptor antagonist, hydroxyflutamide. The relative potency of DHT
      in maintaining DCR was similar to that of progesterone. However, the regression
      of the deciduoma appeared to be advanced in DHT-treated mice. Ovariectomy on Day
      6 of pregnancy resulted in resorption of the conceptus and regression of the
      decidua within 48 h. Treatment with DHT at the time of ovariectomy could not
      prevent fetal resorption, but it delayed the regression of decidua, as indicated,
      in part, by the presence of granulated metrial gland cells. In summary, androgen
      cannot prime the uterus for DCR, but it can maintain DCR once it is induced. The
      physiological significance of this finding remains to be determined.

PMID- 8862768
TI  - Gap junction regulation during preterm labor in the rat: multiple effects of the
      antiprogesterone RU486.
AB  - The objective of the present study was to examine the effects of the
      antiprogesterone RU486 on the expression levels of multiple gap junction (GJ)
      gene products and, in detail, on alpha 1 (connexin43 [Cx43]), in various regions
      of the rat implantation chamber during experimentally induced preterm labor at
      mid/late stages of gestation. Vaginal bleeding, but not expulsion of concepti,
      was observed in a majority of animals 24 h after a single injection of RU486 at
      Day 15 of gestation, and it persisted until animals were killed 48 h later. The
      bleeding was completely suppressed by R 5020, a synthetic progesterone with a
      high affinity for the progesterone receptor (PR). Various components of the
      implantation chamber (uterus, mesometrial stroma, placenta) and ovaries were
      isolated 24 and 48 h postinjection and analyzed for alpha 1 (Cx43), beta 1
      (Cx32), and beta 2 (Cx26) connexin expression by immunohistochemistry and by
      Northern blots (alpha 1 only). Alpha 1 Connexin was present at high levels in the
      myometrium following the inhibition of progesterone action by RU486; accordingly,
      this effect was completely suppressed by R 5020. The blocking of the PR also had
      a dramatic effect on expression levels, size, and distribution of junctional
      plaques composed of beta 1 and beta 2 connexins in polarized luminal and
      glandular epithelium. The average size of junctional plaques was significantly
      reduced in the luminal epithelium after RU486 administration. This effect was
      inhibited in the presence of R 5020. At the RNA level, the alpha 1 transcript was
      markedly elevated in the uterus and in the ovaries 24 and 48 h after
      administration of RU486. An elevation was also observed in the mesometrial
      stroma, while no increase was detected in the placenta. The RU486-induced alpha 1
      mRNA steady-state levels in various tissues were completely suppressed by R 5020.
      These results demonstrate the modulation of multiple connexins in various cell
      types of the implantation chamber upon blocking of PR action. The expression
      profile of the myometrial and epithelial GJs was similar to that previously
      observed in the estrogen-treated rat uterus.

PMID- 8862769
TI  - Determination of activable proacrosin/acrosin in bovine sperm using an
      irreversible isocoumarin serine protease inhibitor.
AB  - The activable proacrosin/acrosin levels in bovine sperm were examined using
      fluorescent staining and flow cytometry. The proportion of sperm with active
      acrosin were determined using the biotinylated isocoumarin serine protease
      inhibitor, Bi-Aca-Aca-OMe-IC (BIC). The presence of bound inhibitor on sperm was
      then determined by secondary labeling with avidin fluorescein conjugate. The
      proportion of sperm with activable proacrosin/acrosin was assessed by using
      detergent treatment to expose the active acrosin in intact sperm. The difference
      between untreated and detergent-treated aliquots was used to estimate the
      proportion of sperm with activable proacrosin/acrosin. In the 24-h stored samples
      from six bulls, the mean proportion of sperm with activable proacrosin/acrosin
      was 78.8 +/- 2.8%, whereas the mean proportion with exposed acrosin after
      cryopreservation of these samples was 55.8 +/- 4.1%. Significant differences (p <
      0.05) were found among bulls in the proportion of sperm with activable
      proacrosin/acrosin both before and after cryopreservation. Activable
      proacrosin/acrosin levels in samples of cryopreserved sperm from five bulls were
      not correlated with fertility. These results do indicate, however, that the
      irreversible isocoumarin serine protease inhibitor BIC can be used to determine
      the proportion of sperm cells that retain activable proacrosin/acrosin after
      cryopreservation and thawing.

PMID- 8862770
TI  - Follicular Atresia, follicular fluid hormones, and circulating hormones during
      the midluteal phase of the estrous cycle in pigs.
AB  - The incidence of atresia, concentrations of follicular fluid steroids, and
      circulating concentrations of estradiol, FSH, and progesterone were investigated
      to determine whether there was any evidence for a wave of follicular activity or
      atresia between Days 7 and 15 of the estrous cycle in pigs, Cyclic pigs (gilts)
      were slaughtered on Days 7, 9, 11, 13, and 15 (4, 4, 4, 4, and 3 pigs per day),
      and 287 follicles > 2 mm were dissected from ovaries to recover follicular fluid
      and granulosa cells. Apoptotic (Ao) granulosa cells were those containing sub
      diploid DNA fluorescence as determined by flow cytometry. follicles with > or =
      10% Ao granulosa cells were classified as atretic, and those with < 10% Ao
      granulosa cells were designated nonatretic. The percentage of atretic follicles
      (AF) per pig was 35.5 +/- 4.7 (mean +/- SEM), and while the percentage of AF
      ranged from 12% to 73%, means did not differ significantly among days. Mean
      follicular estradiol concentration was higher (p < 0.05) in nonatretic follicles
      (NAF) than in AF; in NAF, the concentration decreased (p < 0.05) from 15 ng/ml on
      Day 7 to 2.5 ng/ml on Day 11 and then increased (p < 0.05) to 10 ng/ml on Day 15
      of the cycle. Mean follicular progesterone concentration was higher (p < 0.05) in
      AF than in NAF, while follicular androstenedione concentration (20 +/- 1.5 ng/ml,
      overall mean +/- SEM) did not differ between AF and NAF. Mean plasma estradiol,
      FSH, and progesterone concentrations did not differ among days of the cycle or
      differ significantly during the last 42 h before slaughter. Plasma estradiol and
      FSH concentrations were not significantly correlated with percentage of AF or
      with follicular steroid concentrations. These results support the notion of
      continuous growth and atresia of ovarian follicles in pigs independent of changes
      in plasma FSH and follicular steroid concentration, without evidence for a
      dominant cohort of follicles during the luteal phase of the estrous cycle.

PMID- 8862771
TI  - Differential expression of two beta-galactoside-binding lectins in the
      reproductive tracts of pregnant mice.
AB  - Two beta-galactoside-binding proteins were isolated from uteroplacental complexes
      of pregnant mice and identified as the S-Lac lectins galectin-1 and galectin-3.
      The spatiotemporal pattern of appearance of those proteins was determined by
      immunocytochemistry. Galectin-1 was present in all tissue compartments of the
      uterus except the luminal and glandular epithelium. It was found in the uteri of
      animals from all preimplantation stages of pregnancy, as well as in those from
      nonpregnant, ovariectomized, or sexually immature animals. After implantation of
      the embryo, cells of the decidua basalis were labeled, as were granular metrial
      gland cells, all trophoblastic elements of the placenta, the myometrium, and
      nondecidualized endometrium. By contrast, there was little evidence of galectin-3
      in the uteri of nonpregnant animals or during the preimplantation stages of
      pregnancy. However, immunoreactive material was observed in endometrial cells of
      the primary decidual zone immediately after implantation and at later stages of
      pregnancy in the decidua basalis, metrial gland, and all trophoblastic elements
      of the placenta. There was no evidence of galectin-3 in the myometrium or
      nondecidualized endometrium. After parturition, amounts of galectin-3 in the
      endometrium and metrial triangle appeared to decrease as the implantation sites
      were resorbed. These data suggested that the function of galectin-1 is one of
      tissue maintenance, whereas the function of galectin-3 is related specifically to
      pregnancy.

PMID- 8862772
TI  - Hypothalamic corticotropin-releasing hormone expression in the baboon fetus at
      mid- and late gestation.
AB  - We have proposed that estrogen, via regulation of the placental 11 beta
      hydroxysteroid dehydrogenase (11 beta-HSD) enzyme(s) catalyzing the oxidation of
      cortisol to its inactive metabolite cortisone, regulates the baboon fetal
      pituitary-adrenocortical axis and the onset of de novo production of cortisol by
      the fetus near term. In support of this hypothesis we have demonstrated that the
      increase in expression of the mRNA for the ACTH precursor proopiomelanocortin
      (POMC) in the fetal pituitary and in the specific activity of steroidogenic
      enzymes in the fetal adrenal normally observed at term were enhanced at
      midgestation by maternal estrogen administration. However, it is not known
      whether activation of the fetal pituitary reflects a concomitant increase in
      corticotropin-releasing hormone (CRH) mRNA expression and/or peptide production
      by the fetal hypothalamus. Therefore, an aim of the present study was to
      determine whether the increase in POMC mRNA in fetal baboons delivered at term,
      and at midgestation to mothers treated with estradiol, reflected an increase in
      hypothalamic CRH. Fetal hypothalami were obtained on Day 100 (n = 6) and Day 165
      of gestation (term = Day 184) from untreated baboons (n = 5) and on Day 100 from
      baboons (n = 4) whose mother had been treated daily with 1.0 mg estradiol on Days
      70 to 100. Hypothalamic CRH peptide concentrations were determined by RIA, and
      CRH mRNA expression was quantified by in situ hybridization in sections of the
      fetal hypothalamus through the paraventricular nucleus (PVN) using a 48-base
      synthetic oligodeoxynucleotide probe 3' end-labeled with [35S]dATP. The mean (+/-
      SE) maternal serum estradiol concentration in baboons treated with estradiol at
      midgestation (2.4 +/- 0.4 ng/ml) was greater (p < 0.05) than that in untreated
      baboons on Day 100 (1.0 +/- 0.2), but similar to that in late gestation (2.0 +/-
      0.2). The mean steady-state concentration of CRH in the baboon fetal hypothalamus
      at midgestation (15.8 +/- 6.0 ng/g tissue) was not altered in fetuses whose
      mothers had been treated with estradiol (17.6 +/- 0.9 ng/g). Hypothalamic CRH
      concentrations in fetal baboons of late gestation (20.7 ng/g; n = 2) were also
      similar to mean CRH values measured at midgestation but, owing to the marked
      increase in weight of the fetal hypothalamus with advancing pregnancy, the
      content of hypothalamic CRH in late gestation (28.8 ng/structure) exceeded (p <
      0.01) that at midgestation. Mean levels of CRH mRNA at midgestation when
      expressed per cell (17.4 +/- 1.3 grains per cell) or per unit area of PVN (375 +/
      20 grains per area) were similar to respective values in late gestation (18.3 +/
      1.1 grains per cell; 350 +/- 55 grains per area; n = 3 per group). These
      findings support the suggestion that the increase in fetal pituitary POMC mRNA
      expression and ACTH peptide previously reported to occur normally between
      midgestation and term are not associated with a concomitant increase in
      hypothalamic CRH peptide or CRH mRNA concentrations. Moreover, it would appear
      that by midgestation, hypothalamic CRH is available in adequate concentrations to
      "drive" the fetal pituitary and that it is the levels of maternal cortisol
      arriving within the fetal circulation, as dictated by estrogen-regulated
      placental 11 beta-HSD-oxidase activity, that establish the extent to which the
      fetal pituitary responds to CRH.

PMID- 8862773
TI  - Androgen and pituitary control of penile nitric oxide synthase and erectile
      function in the rat.
AB  - Castration of adult male rats reduces by half the penile erectile response to
      electrical field stimulation (EFS) of the cavernosal nerve, and the activity of
      penile nitric oxide synthase (NOS). Both changes are prevented by androgen
      administration. We have now investigated whether other strategies of androgen
      ablation or competition may act as stronger inhibitors, and, if so, whether the
      stronger inhibition is due to the depletion of penile NOS content. Rats were
      castrated or left intact and were treated daily as follows: 1) intact, with the
      antiandrogen flutamide (25 mg/kg/day, i.p.); 2) castrated, with similar
      treatment; 3) castrated, with 17 beta-estradiol 3-benzoate (estradiol; via
      silastic tubing, s.c.). Additional groups of intact rats received injections of a
      GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysectomized and left
      untreated. Controls were untreated intact and castrated animals. After 7 days,
      rats were subjected to EFS, and the ratios between maximal intracavernosal
      pressure (MIP) and mean arterial pressure (MAP) were measured. Penile NOS
      activity and the contents of neuronal NOS (nNOS) and endothelial NOS (eNOS) were
      determined. Castration reduced the MIP:MAP ratio and penile NOS activity.
      Androgen receptor blockade with flutamide induced a similar response in intact
      rats. When flutamide treatment was combined with castration, the erectile
      response was nearly abolished, but NOS activity was not decreased below the
      values in castrated rats. Estradiol given to castrated rats and hypophysectomy or
      GnRHA treatment in intact rats diminished the erectile response below the level
      in castrated animals. In hypophysectomized rats, penile NOS activity fell below
      levels in castrated animals. contents of nNOS and eNOS were not significantly
      reduced by any treatment. These data suggest that penile erection in the rat is
      completely dependent on androgens, presumably because of their role in the
      maintenance of penile NOS activity and of other ancillary factors. However, only
      the complete blockade of residual androgen effects at the tissue level or a total
      androgen depletion can abolish the erectile response.

PMID- 8862774
TI  - Characterization of porcine endometrial, myometrial, and mammary oxytocin binding
      sites during gestation and labor.
AB  - Changes in oxytocin (OT) receptor expression have been found to be an important
      determinant of the physiological effect of OT in several species. To date there
      are no published studies of OT binding sites during pregnancy in the pig. The
      purpose of the present study is to improve understanding of the role of OT in
      porcine parturition. The concentration and affinity of OT binding sites were
      determined for myometrium and endometrium from pregnant and postpartum gilts.
      Tissues were obtained after slaughter from 7 animals in each of four groups: 1)
      90 days gestation, 2) 112 days gestation, 3) term after milk letdown (before
      delivery), and 4) within 1-3 h after farrowing. Mammary tissues were obtained for
      some animals in each group (n = 3-5/group). Before slaughter, blood was collected
      from each animal and assayed for estradiol-17 beta, progesterone, 13,14-dihydro
      15-keto-prostaglandin F2 alpha (PGFM), and OT. Binding of 3H-OT in the three
      tissues was concentration- and time-dependent. Sites of 3H-OT binding (fmol/mg
      protein +/- SEM) increased toward term for each tissue and remained elevated in
      the postpartum group. Endometrial and mammary tissues displayed the most acute
      increases in OT binding site concentrations while myometrial tissues displayed a
      more gradual increase in OT binding sites over the times studied. The binding
      sites displayed high affinity for 3H-OT and were characterized by linear
      Scatchard plots. Concentrations of estradiol-17 beta, PGFM, and OT (pg/ml +/-
      SEM) were positively correlated with 3H-OT binding site concentrations, whereas
      progestrone concentrations (ng/ml +/- SEM) were negatively correlated with
      binding site concentration, as determined by Pearson's Correlation Analysis. The
      data represent the first account of changes in the expression of OT binding sites
      on porcine tissues during gestation and labor.

PMID- 8862775
TI  - Maternal recognition of pregnancy in swine. I. Minimal requirement for exogenous
      estradiol-17 beta to induce either short or long pseudopregnancy in cycling
      gilts.
AB  - Five experiments were conducted to determine the minimal requirement for
      estradiol-17 beta (E2) injections to induce either short pseudopregnancy (SPP) or
      long pseudopregnancy (LPP) in cycling gilts. In experiments 1 through 5, E2 was
      injected i.m. on combinations of days between 11 and 25 days postestrus.
      Exogenous E2 on Days 12 and 13 or on Days 12 through 19 was optimal for induction
      of SPP or LPP, respectively. The duration of E2-induced diestrus was clearly
      demarcated between SPP (n = 73, duration 23-35 days) and LPP (n = 23, duration >
      50 days). A sixth experiment was conducted to determine the minimum dose of
      intrauterine E2 required to induce SPP, and these gilts received intrauterine
      infusions of 0, 4, 40, or 400 micrograms E2 per 24 h on Days 12 and 13
      postestrus. Pseudopregnancy was induced in 0 of 12, 1 of 4, 1 of 11, and 4 of 7
      gilts in the treatment groups, respectively. These data suggest that uterine
      exposure alone is not sufficient to induce SPP. The present results indicate that
      the optimal signal for inducing LPP in unmated cycling gilts, and perhaps also
      for maternal recognition of pregnancy in mated gilts, may occur in two phases
      with continuous exposure to E2 being required from Day 12 to Days 17-19.

PMID- 8862776
TI  - Maternal recognition of pregnancy in swine. II. Plasma concentrations of
      progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha during the estrous
      cycle and during short and long pseudopregnancy in gilts.
AB  - Two experiments were conducted to determine plasma progesterone (P4) and 13,14
      dihydro-15-keto-prostaglandin F2 alpha (PGFM) concentrations in unmated gilts
      induced to have either short pseudopregnancy (SPP) or long pseudopregnancy (LPP).
      In experiment 1, estradiol-17 beta (E2) was injected on different combinations of
      days between Days 11 and 16 of the estrous cycle. For gilts induced to exhibit
      SPP, the interestrous interval averaged 27.0 +/- 0.4 days compared to the control
      interval of 20.0 +/- 0.4 days. In experiment 2, E2 injections were given on Days
      12 and 13 or on Days 12 through 25. Interestrous intervals in SPP and
      nonpseudopregnant gilts were 25.6 +/- 0.2 and 19.9 +/- 0.6 days, respectively.
      Four of six gilts treated with E2 on Days 12-25 were induced to have LPP lasting
      more than 100 days. In both experiments, plasma P4 declined to baseline
      approximately 3 days before posttreatment estrus, regardless of type of
      pseudopregnancy induced. Plasma PGFM peaked 4-6 days before posttreatment estrus
      in gilts displaying each type of response. In gilts exhibiting LPP, plasma PGFM
      concentrations tended to increase steadily during pseudopregnancy. These data
      suggest that the mechanisms of luteolysis during the estrous cycle of unmated
      gilts and during estrogen-induced SPP and LPP may be similar. The present results
      suggest that luteal persistence during SPP and LPP may be due to delayed peak
      release of prostaglandin F2 alpha by the uterus.

PMID- 8862777
TI  - Effects of phosphate on in vitro 2-cell block of AKR/N mouse embryos based on
      changes in cdc2 kinase activity and phosphorylation states.
AB  - This study demonstrated the effects of phosphate on the 2-cell block of AKR/N
      mouse embryos at the molecular level and focused on changes in the kinase
      activity and the phosphorylation state of cdc2, which is shown to regulate the
      cell division cycle. Removal of phosphate from the culture medium dramatically
      increased developmental rates to the 4-cell (91.8%) and blastocyst (42.6%) stages
      compared with those of embryos cultured in 1.17 mM phosphate (3.3% and 0%,
      respectively). The rate of development to the 4-cell stage was significantly
      inhibited by 0.001 mM phosphate (p < 0.05), and no morula formation was observed
      at 1.0 mM. The patterns of cdc2 kinase activity during the first cell cycle in
      AKR/N embryos were similar to those of control MCH embryos, showing the highest
      activity at M phase and low activity during the interphase. The phosphorylated
      form of cdc2 increased during the interphase, indicating that the synthesis of
      cyclin B and accumulation of inactive pre-maturation-promoting factor (pre-MPF)
      as well as abrupt dephosphorylation of cdc2 at the first cleavage correlated with
      the activation of cdc2 kinase. When phosphate was absent, the activation pattern
      of cdc2 kinase during the second cell cycle in AKR/N embryos was similar to that
      in the first cell cycle. On the other hand, no dephosphorylation of cdc2 was
      observed and the kinase activity remained at a low level until 56 h after
      insemination in the presence of phosphate, although an increase in phosphorylated
      cdc2 was observed as in the phosphate-free group. Treatment of AKR/N embryos
      arrested at the 2-cell stage with okadaic acid resulted in the dephosphorylation
      and activation of cdc2, confirming the presence of a sufficient amount of pre
      MPF. These results show that phosphate has a deteriorative effect on the in vitro
      development of AKR/N embryos and suggest that this effect was not on the
      synthesis of cyclin B but on the dephosphorylation of phosphorylated cdc2.

PMID- 8862778
TI  - Identification of prometalloproteinase-3 as a major protein secreted by human
      endometrial fibroblasts and inhibited by coculture with trophoblast cells.
AB  - To assess endometrial fibroblast-cytotrophoblast interactions, we used a
      coculture system allowing analysis of the potential cell morphology modifications
      and protein secretion variations possibly involved in endometrial invasion
      arrest. Stromal cells and cytotrophoblasts were isolated from endometrial
      biopsies and first-trimester placental villi, respectively. In our culture
      conditions, a 57-kDa protein that was secreted by cultured fibroblasts but was
      absent in the 4-day coculture medium was found to be identical to
      prometalloproteinase-3 (proMMP-3) through determination of amino acid sequences
      of NH2-terminal and internal peptides. Northern blotting analysis of endometrial
      fibroblast total RNA showed a 38.6% metalloproteinase-3 (MMP-3) mRNA inhibition
      by 4-day 10(-6) M R5020 treatment. Inhibition of proMMP-3 secretion was weak when
      cytotrophoblasts were cultured for 4 days in a polycarbonate membrane insert over
      cultured fibroblasts without possible cell contact in spite of high levels of
      progesterone produced by cytotrophoblasts. Furthermore, cytotrophoblasts cultured
      on a monolayer of endometrial fibroblasts became syncytia, and most of the
      fibroblasts were decidualized. The closeness of the two cell types allowed
      paracrine relationships that might facilitate the progesterone action. Since MMP
      3 is known to activate collagenases, inhibition of its secretion by cell contact
      might be a mechanism of invasion arrest for trophoblast cell migration.

PMID- 8862779
TI  - Characterization of a polarized porcine uterine epithelial model system.
AB  - A porcine uterine epithelial cell (pUE) culture system that retains structural
      and functional properties of the surface epithelium in vivo was developed.
      Uterine luminal epithelial cells were isolated after pancreatin-dispase enzymatic
      release of epithelium from hysterectomized gilts. Cells were seeded on Millicell
      filters precoated with Matrigel in 24-well plates and subsequently allowed to
      proliferate to confluence. Purity of the isolation was confirmed by the presence
      of > 99% cytokeratin-positive cells. Epithelial cells became polarized in vitro
      and compared favorably in morphology to uterine epithelial cells in situ once a
      transepithelial resistance of > 600 omega cm2 was established. Microscopic
      analysis confirmed the presence of a simple columnar epithelium with prominent
      microvilli on the apical cell surface and a well-developed junctional complex
      containing tight junctions, belt and spot desmosomes, and interdigitating lateral
      cell processes. Indirect immunofluorescence of the tight junction-associated
      protein, ZO-1, indicated the formation of tight junctional complexes in the
      subapical region of the polarized cells. Functional polarity of epithelial
      cultures was also verified by 1) electrical resistance measurements, 2) basal
      preference for the secretion of prostaglandins F2 alpha and E2, 3) apical
      preference for the release of 35S-methionine-incorporated secretory proteins, and
      4) apically and basally distinct secretory protein profiles. Steroid treatment
      (estrogen, progesterone, or estrogen plus progesterone) of the polarized pUE
      cells affected the release of radiolabeled methionine-incorporated secretory
      proteins. In addition, the protein profiles as compared to samples treated with
      fetal bovine serum or charcoal/dextran-stripped fetal bovine serum were altered.
      Steroid treatments did not alter the electrical resistance or the basal
      preference for prostaglandin secretion. This culture system may be useful for in
      vitro analysis of maternal recognition of pregnancy paradigms as well as the
      study of the direct actions of hormones, prostaglandin secretion, and epithelial
      stromal interactions.

PMID- 8862780
TI  - Diploid expression of human leukocyte antigen class I and class II molecules on
      spermatozoa and their cyclic inverse correlation with inhibin concentration.
AB  - A diploid expression of class I and class II human leukocyte antigens (HLA) has
      been found in purified spermatozoa by using double fluorescence labeling
      cytofluorometry and relevant monoclonal antibodies; this expression has been
      confirmed for the first time by the analysis of specific HLA mRNA and metabolic
      35S labeling followed by immunoprecipitation, which demonstrates an active
      ongoing translation of HLA proteins in germinal cells. Long-living mRNA coming
      from diploid germinal cells may be translated to HLA molecules in spermatozoa.
      This translation is controlled (or at least inversely correlated) by a testicular
      hormone (inhibin) in a cyclic fashion. Remarkably, serum levels of inhibin,
      synthesized by Leydig and Sertoli cells, follow a 12- to 13-day cycle, with a
      peak level at Day 6; this is probably controlled by FSH (not cyclic in males) and
      other testicular and/or unknown hormones. Peak levels of inhibin concur with the
      lower density and percentage of spermatozoa expressing both HLA class I and II
      molecules (close to 3% by cytofluorometry); lowest levels of inhibin coincide
      with the highest numbers (35-40%) of spermatozoa positive for both HLA molecules
      and a higher surface density. These observations could put to an end a
      disconcerting and long-lasting controversy on the expression/non-expression of
      HLA antigens on spermatozoa. The possibility that HLA-bearing spermatozoa are
      more capacitated for fertilization than those that do not bear HLA, and the
      implications of our results on male fertility control are also discussed.

PMID- 8862781
TI  - Xrcc-1 expression during male meiosis in the mouse.
AB  - XRCC1 is involved in DNA strand-break repair, homologous recombination, and
      sister chromatid exchange and is expressed as a low-abundance mRNA with elevated
      expression in testis. The purpose of this study was to determine whether specific
      spermatogenic cell types have elevated Xrcc-1 expression and whether expression
      levels change in the testis with increased age. Northern blot analysis of mRNA
      prepared from testes of 15-, 25-, and 60-day-old mice revealed a single
      hybridizing band of 2.2 kb. Quantitative RNase protection assays revealed no
      changes in the level of Xrcc-1 expression in testis relative to DNA content among
      6-, 12-, 18-, 24-, or 28-mo-old mice. Finally, reverse transcription coupled
      polymerase chain reaction amplification results demonstrated that Xrcc-1
      expression is most abundant in pachytene spermatocytes and round spermatids with
      low expression in Sertoli cells, types A and B spermatogonia, preleptotene
      spermatocytes, and leptotene plus zygotene spermatocytes. The relatively abundant
      Xrcc-1 expression in pachytene spermatocytes and round spermatids suggests that
      Xrcc-1 is involved in DNA strand-break repair associated with meiotic
      recombination in addition to its previously implicated role in strand-break
      repair associated with base excision repair.

PMID- 8862782
TI  - Three forms of gonadotropin-releasing hormone in a perciform fish (Sparus
      aurata): complementary deoxyribonucleic acid characterization and brain
      localization.
AB  - Three forms of GnRH-salmon (sGnRH), seabream (sb-GnRH), and chicken (cGnRH-II)
      have been described in the gilthead seabream (Sparus aurata) brain, and the cDNA
      encoding the sbGnRH precursor was recently isolated. In the present study, the
      cDNAs encoding the sGnRH and cGnRH-II were isolated and characterized, and the
      neurons producing the three GnRHs were localized in the seabream brain. Fragments
      of sGnRH and cGnRH-II cDNAs were amplified by polymerase chain reaction and used
      as probes to isolate the full-length cDNAs from a brain cDNA library. The cDNA
      encoding the cGnRH-II precursor is 573 nucleotides (nt) long, and the cDNA
      encoding the sGnRH precursor is 1971 nt in length with an unusually long 5'
      untranslated region. Specific single-strand DNA probes for in situ detection of
      mRNA were designed according to nonconserved regions among the three GnRH c-DNAs.
      Localization of GnRH mRNA-producing cells in the brain revealed five distinct
      populations of cells: sGnRH-producing cells in the ventromedial olfactory bulbs
      and the terminal nerve, sbGnRH-producing cells in the preoptic area and the
      ventral thalamus, and cGnRH-II-producing cells in the midbrain tegmentum. The
      discrete sites of expression of the three forms of GnRH indicate that only sbGnRH
      is directly involved in the control of gonadotropin secretion.

PMID- 8862783
TI  - Characterization of a vitellogenin receptor in white perch (Morone americana).
AB  - Receptors for white perch vitellogenin (wVTG) were characterized using wVTG,
      labeled in vivo with [3H]leucine or in vitro with 125I, and semipurified ovarian
      membranes. Specific binding of wVTG to the membranes was temperature-dependent,
      proportional to the amount of membrane, and saturable. Scatchard analyses
      revealed a single class of binding sites of low maximum binding capacity (MBC;
      approximately 35 pmol VTG/mg membrane protein) and high affinity (Kd
      approximately 400 nM), consistent with wVTG levels (540-2700 nM) circulating in
      maturing females. Ligand blotting revealed a receptor protein of M(r)
      approximately 157000 and a smaller protein, possibly its degradation product.
      Striped bass vitellogenin, chicken egg yolk very low density lipoprotein, and
      suramin displaced wVTG from its receptor, but BSA did not. No change in Kd was
      noted over the course of vitellogenesis in maturing perch, and MBC increased only
      slightly very late in the gametogenic cycle. The wVTG bound specifically to
      membranes prepared from liver, muscle, and mesenteric fat, but not to erythrocyte
      membranes. The Kd for ovary (394 nM) and liver (345 nM) were similar, but the Kd
      for muscle (1440 nM) was much higher.

PMID- 8862784
TI  - Changes in uterine secretion of prostaglandin F2 alpha in response to oxytocin
      during the estrous cycle, early pregnancy, and estrogen-induced pseudopregnancy
      in swine.
AB  - Thirty-one sows were used in an experiment designed to determine whether the
      ability of the porcine uterus to release prostaglandin (PG) F2 alpha in response
      to oxytocin was suppressed in pregnancy and pseudopregnancy. Sows were assigned
      to one of three treatment groups: nonbred (nonpregnant) controls (n = 8),
      pseudopregnant (5 mg estradiol benzoate, i.m., daily on Days 11-15 postestrus; n
      = 8), or bred (bred once daily throughout the estrous period; n = 15). Jugular
      venous blood samples were collected daily for quantification of progesterone.
      Pregnancy was determined by uterine examination at slaughter 51-72 days
      postmating. On the basis of progesterone and embryo recovery, bred sows were
      classified into three subgroups: confirmed pregnant (n = 4), suspected pregnant
      based on delayed luteal regression (n = 5), or bred/not pregnant (n = 6). All
      sows received an injection of oxytocin (30 IU, i.v.) on Days 12, 15, and 18
      postestrus. Jugular venous blood samples were collected from 60 min prior to
      through 120 min after injection of oxytocin for quantification of 13, 14-dihydro
      15-keto-PGF2 alpha (PGFM). Magnitude of response above baseline and area under
      the PGFM response curve (AUC) were calculated for each sow on each day and
      compared among treatment groups by analysis of variance. Responses in pregnant
      and suspected-pregnant sows were not different on any day examined; therefore the
      two groups were combined (n = 9) and considered pregnant for all subsequent
      analyses. Responses in the nonpregnant and bred/not pregnant sows were pooled and
      compared to the responses in the pregnant and pseudopregnant sows. Magnitudes of
      response were similar between these pooled groups on Day 12 (p > 0.5), but were
      less in pregnant and pseudopregnant sows on Days 15 and 18 (p < 0.01). When
      nonpregnant and bred/not pregnant sows were compared to each other, the
      magnitudes of the response were similar on Days 12, 15, and 18 (p > 0.3 on each
      day). In contrast, when pregnant and pseudopregnant sows were compared,
      pseudopregnant sows had a lower magnitude of response that was consistent across
      all 3 days (p < 0.02). Similar relationships were apparent for the AUC. These
      results demonstrate that uterine secretory responsiveness to oxytocin is
      suppressed during early pregnancy and that this effect may be mediated through
      estrogen secreted by conceptuses.

PMID- 8862785
TI  - Development of luteinizing hormone action in the perinatal rat ovary.
AB  - The expression of LH receptor (LHR) mRNA was studied in fetal rat gonads using
      polymerase chain reaction multiplication of reverse-transcribed mRNA. A primer
      pair corresponding to the extracellular domain of the receptor revealed the
      expression of LHR mRNA in fetal ovaries and testes as early as embryonic Day
      13.5, the earliest age studied. The localization of LHR mRNA was examined in the
      perinatal rat ovary using in situ hybridization with two antisense probes, one
      encoding the extracellular and the other encoding the transmembrane domains of
      LHR. At the age of 4 days, only the extracellular LHR probe gave specific signal
      over ovarian stromal and follicular cells, excluding the ova. Three days later,
      similar distribution of specific hybridization was observed with both probes. In
      the 10- and 30-day-old rat ovaries, clear expression of LHR mRNA was found to be
      with both probes in theca cells. Gonadotropin-stimulated production of cAMP was
      studied in cultures of dispersed perinatal rat ovarian cells. When 5-day-old
      ovarian cells were cultured for 3 days in vitro and then stimulated by either hCG
      (0.1 mg/L) or FSH (1 mg/L) for 6 h, cAMP production was enhanced only in cells
      stimulated by FSH. In a similar experiment with 7-day-old ovarian cells, cAMP
      production was stimulated by both FSH and hCG. Stimulation with hCG (0.1 mg/L)
      during the 3-day culture caused homologous desensitization of cAMP production,
      but stimulation with FSH (0.1 mg/L) had no such effect. The desensitization of
      the LHR was also investigated by treating neonatal rats in vivo with a high dose
      of hCG (600 IU/kg BW s.c. as a single injection on Day 7) or with a dosage of
      recombinant human (rec) FSH on Days 3-9 (0.3 IU s.c twice daily). Thereafter, at
      the age of 10 days, the ovaries were incubated either with recFSH (200 IU/L) or
      hCG (CR-121; 0.1 mg/L) for 1 h. Homologous desensitization of cAMP production by
      hCG was observed, but the FSH-mediated cAMP production was not affected. The hCG
      induced steroidogenesis (progesterone and testosterone production) was not
      desensitized. In conclusion, these findings indicate that 1) the expression of
      the mRNA encoding the extracellular domain of LHR, i.e., truncated receptor,
      occurs in fetal rat gonads as early as embryonic Day 13.5; 2) the expression of
      the truncated LHR mRNA occurs uniformly in the differentiating ovarian cells
      before the appearance of the functional theca cell layer; 3) full-length LHR
      message appears in the developing ovary concomitantly with appearance of
      differentiated theca cells; 4) homologous desensitization of cAMP output by hCG,
      without steroidogenic desensitization, is present in perinatal rat ovaries; and
      5) no FSH-evoked desensitization of cAMP production occurs in perinatal ovaries.

PMID- 8862786
TI  - Effects of relaxin on lactational performance in ovariectomized gilts.
AB  - In gilts, mammary lobulo-alveolar growth begins on about Day 80 of gestation and
      continues progressively until term. Relaxin in concert with estrogen plays a
      major role in promoting this mammary gland growth. The present study was
      conducted to determine the importance for lactational performance of prepartum
      relaxin-dependent growth of the mammary glands in ovariectomized gilts given
      progesterone to maintain pregnancy. Twenty-four gilts were either sham
      ovariectomized or bilaterally ovariectomized and assigned to four treatment
      groups: sham-ovariectomized control, ovariectomized progesterone-treated,
      ovariectomized progesterone- and (starting at Day 80) relaxin-treated, and
      ovariectomized progesterone- and (starting at Day 100) relaxin-treated. Piglets
      were delivered by cesarian section, and gilts were given uniform colostrum
      replete foster litters (born of untreated mothers) to nurse from Day 1 to Day 28
      of lactation. Prepartum mammary development appeared by visual examination to be
      greatly reduced in relaxin-deficient gilts. Stimulus of the mammary nipples by
      the nursing piglets, however, appeared to overcome relaxin-dependent differences
      in mammary development among treatments. There was no effect of treatment on the
      time piglets spent at the udder, piglet mortality, piglet weight at Day 21 of
      lactation, milk composition, mammary cross-sectional area, or sow weight change
      during lactation. We conclude that gilts devoid of circulating luteal relaxin can
      display normal lactational performance when given colostrum-replete foster
      litters.

PMID- 8862787
TI  - Low density lipoprotein receptor-related protein-2 expression in efferent duct
      and epididymal epithelia: evidence in rats for its in vivo role in endocytosis of
      apolipoprotein J/clusterin.
AB  - Apolipoprotein J/clusterin/sulfated glycoprotein-2 (apo J) disassociates from
      spermatozoa and is endocytosed by epithelial cells lining the efferent ducts and
      epididymis. The low density lipoprotein receptor-related protein-2/megalin (LRP
      2) has been shown to bind to apo J and mediates its endocytosis and lysosomal
      degradation in cultured cells. In this study, immunocytological techniques were
      used to localize LRP-2 in rat efferent ducts and epididymis and to determine
      whether its expression correlated with those epithelial cells involved in apo J
      endocytosis. Pronounced LRP-2 immunochemical staining was observed on the apical
      surfaces of epithelial cells lining the efferent ducts and in the intermediate
      zone, proximal caput, and corpus and cauda regions of the epididymis. Single
      immunogold labeling at the electron microscopic level showed LRP-2 to be present
      within coated pits, endocytic vesicles, and early endosomes of the nonciliated
      cells of the efferent ducts and the principal cells of the epididymis. In
      efferent ducts, double immunogold labeling showed both LRP-2 and apo J to be
      present in endocytic compartments including coated pits, endocytic vesicles, and
      early endosomes of nonciliated cells. However, while apo J was detected in late
      endosomes and lysosomes of nonciliated cells, LRP-2 was not. Apical tubules,
      possibly emerging from late endosomes, contained labeling for LRP-2 but not for
      apo J. Ciliated cells lying adjacent to nonciliated cells displayed no labeling
      for either LRP-2 or apo J. These results are consistent with the possibility that
      LRP-2 serves as an endocytic receptor for apo J in vivo and that after
      endocytosis the LRP-2 is recycled back to the cell surface while apo J is
      delivered to the lysosomes for degradation. To provide additional evidence
      implicating LRP-2 in apo J endocytosis, a receptor-associated protein (RAP), an
      antagonist of apo J binding to LRP-2, was injected into the efferent duct lumen.
      Subsequent immunocytological analysis of the efferent duct showed that the RAP
      treatment abolished the endocytosis of apo J by the nonciliated cells. Taken
      together, these data indicate that LRP-2 is a likely mediator of apo J
      endocytosis by the nonciliated efferent duct cells.

PMID- 8862788
TI  - Cyclic adenosine 3',5'monophosphate-dependent regulation of protein tyrosine
      phosphorylation in relation to human sperm capacitation and motility.
AB  - The involvement of cAMP in the process of sperm capacitation has been the subject
      of several studies. In addition, the importance of protein-tyrosine
      phosphorylation in this process has been investigated, although only a few
      studies have been reported in the human. Since agents regulating the
      intracellular concentrations of cAMP affect sperm capacitation rates, the role of
      cAMP on the expression of phosphotyrosine-containing proteins was investigated
      during human sperm capacitation. Fetal cord serum ultrafiltrate, a known
      capacitation inducer in human spermatozoa, caused an increase in the
      phosphotyrosine content of 105- and 81-kDa proteins (p105 and p81), the two major
      phosphotyrosine-containing proteins of human spermatozoa. Similar effects were
      observed when spermatozoa were incubated with phosphodiesterase inhibitors or
      cell-permeant cAMP analogs, suggesting that cAMP is involved in these two
      processes. Forskolin, an adenylyl cyclase activator, also caused an increase in
      both sperm capacitation rates and tyrosine phosphorylation of p105 and p81, while
      12-O-tetradecanoyl phorbol 13-acetate stimulated both capacitation and tyrosine
      phosphorylation of p105 and p81 only when spermatozoa were incubated in the
      presence of bicarbonate, in agreement with its reported effects on cAMP
      production and hamster sperm capacitation. The inhibition of these phenomena by
      cAMP-dependent protein kinase inhibitors, and the stimulation by protein
      phosphatase inhibitors, suggest that Ser/Thr protein phosphorylation plays an
      important role in the regulation of both sperm capacitation and protein-tyrosine
      phosphorylation pathways. However, observations that both calyculin A and okadaic
      acid stimulated sperm capacitation, whereas only calyculin A increased p105 and
      p81 phosphotyrosine content and sperm velocity, suggest that protein phosphatase
      PP1 is involved in the two latter phenomena while PP2A mediates sperm
      capacitation. These results suggest that divergent pathways might regulate
      tyrosine phosphorylation of p105 and p81 and sperm capacitation after cAMP
      dependent phosphorylation of an intermediate protein.

PMID- 8862789
TI  - Effects of gonadotropin treatment and withdrawal on follicular growth, cell
      proliferation, and atresia in ewes.
AB  - To determine the effects of FSH-P treatment and subsequent withdrawal on
      follicular growth, cell proliferation, and atresia, ewes (n = 4 ewes/treatment
      group) received twice daily injections of saline or FSH-P beginning on Day 13 of
      the estrous cycle (length of the estrous cycle = 16.5 days) and were slaughtered
      after 0, 48, or 72 h of treatment (i.e., on Days 13, 15, or 16). Some treatment
      groups received FSH-P from Day 13 until slaughter (FSH-P-treated), whereas some
      received FSH-P for 24-48 h followed by saline for 24-48 h (FSH-P withdrawal). All
      ewes received an i.v. injection of bromodeoxyuridine (BrdU, a thymidine analogue)
      1 h before slaughter. For both ovaries from each ewe, the number and surface
      diameter of all visible antral follicles were determined, and antral follicles
      were classified as small (< or = 3 mm), medium (> 3 mm to < or = 6 mm), or large
      (> 6 mm). As an index of the rate of cell proliferation, BrdU was immunolocalized
      in paraffin-embedded tissue sections, and the labeling index (LI; BrdU-labeled
      nuclei as a percentage of total nuclei) was determined for granulosa and thecal
      cells of nonatretic and early atretic antral follicles of known diameter.
      Follicular status (atretic vs. nonatretic) was evaluated morphologically.
      Moreover, the presence of apoptosis was detected in situ by using the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling method. For
      untreated and saline-treated ewes, the number of small follicles per ewe
      increased (p < 0.01) from Day 13 to Day 15, then decreased again on Day 16,
      whereas numbers of medium and large follicles did not differ across days.
      Compared with saline-treated ewes, ewes receiving FSH-P from Day 13 until
      slaughter had fewer (p < 0.05) small but more (p < 0.05) medium and large
      follicles. Compared with FSH-P-treated ewes, FSH-P withdrawal resulted in fewer
      (p < 0.05) medium and large but more (p < 0.05) small follicles. Across all
      follicular size classes, granulosa and thecal cell LI of nonatretic follicles was
      decreased (p < 0.05) by FSH-P withdrawal compared with FSH-P treatment.
      Additionally, across all follicular size classes, FSH-P withdrawal increased (p <
      0.01) the percentage of follicles that were atretic compared with saline or FSH-P
      treatment. Histochemical staining of early and advanced atretic follicles showed
      that granulosa cells are the predominant site of cell death (apoptosis) during
      follicular atresia. Thus, compared with continuous FSH-P treatment, withdrawal of
      FSH-P resulted in decreased numbers of medium and large follicles, decreased
      proliferation of follicular cells, and an increased incidence of atresia
      associated with granulosa cell death. This model should prove useful for studying
      the mechanisms regulating follicular growth and atresia in ewes.

PMID- 8862790
TI  - Development of ovine embryos in synthetic oviductal fluid containing amino acids
      at oviductal fluid concentrations.
AB  - The effects of supplementing synthetic oviductal fluid (SOF) with amino acids, at
      oviductal fluid concentrations, on the development of ovine in vitro-matured/in
      vitro-fertilized embryos was examined in three experiments. In the first, embryo
      development in SOF, SOF + 2% human serum (HS), SOF + 20% HS, and SOF + BSA, with
      and without amino acid supplementation, was examined. Development of zygotes to
      the blastocyst and hatching blastocyst stages was highest in medium containing
      20% HS (64.8% and 54.4%, respectively) irrespective of amino acid
      supplementation. However, supplementation was significantly beneficial in all
      other media, with up to 42.1% of zygotes developing into hatching blastocysts. In
      these media, supplementation also significantly increased the mean number of
      nuclei per newly formed blastocyst (up to a mean of 70.8) and reduced the time
      during which blastocysts formed. Experiment 2 was an examination of the effect on
      embryo development of three amino acid preparations (oviduct amino acid
      concentrations vs. Eagle's Basal Medium (BME) essential + Minimum Essential
      Medium (MEM) nonessential vs. MEM essential + MEM nonessential concentrations)
      and the presence or absence of BSA. Both the amino acid and BSA treatments
      significantly influenced the percentage of zygotes that developed to the hatching
      blastocyst stage but not to the blastocyst stage. The preferred medium contained
      amino acids at oviductal fluid concentrations and BSA (54.5% hatching rate). The
      amino acid treatments did not significantly influence the mean number of nuclei
      per newly formed blastocyst, but the addition of BSA had a significant effect
      (70.7 +/- 1.14 vs. 75.7 +/- 1.13). In experiment 3, embryo development to Day 13
      was examined after culture in SOF containing amino acids at oviductal fluid
      concentrations. Embryos were cultured in the presence of either BSA, polyvinyl
      alcohol (PVA), or no additional supplement and were transferred to recipient ewes
      on either Day 0 (after in vitro fertilization), 3, or 5. The addition of BSA or
      PVA had no significant effect, but significantly more embryos developed to Day 13
      following transfer on Day 0 (60.0%) than on either Day 3 or 5 (overall 45.4%). It
      is concluded that SOF containing oviductal fluid concentrations of amino acids 1)
      facilitates the development of a high percentage (57.5%) of blastocysts, 2)
      improves embryo morphology compared with that observed in medium containing HS,
      3) significantly improves hatching rates compared with those obtained in SOF
      containing commercially available preparations of amino acids, and 4) produces
      embryos with relatively high levels of viability to Day 13 of pregnancy.

PMID- 8862791
TI  - Normal mice develop from oocytes injected with spermatozoa with grossly misshapen
      heads.
AB  - Because in the mouse some structurally abnormal spermatozoa can penetrate
      oocytes, we decided to determine whether mouse oocytes fertilized by spermatozoa
      with grossly misshapen heads are able to develop normally. We injected such
      spermatozoa from BALB/c mice individually into mature oocytes of hybrid mice
      B6D2F1. Eighty to ninety percent of the oocytes were activated and developed into
      blastocysts in vitro and, when transferred to foster mothers, some developed into
      apparently normal fertile adults. This finding indicates that a proportion of
      abnormal spermatozoa carry all the genome and organelles necessary for normal
      embryonic development and growth to fertile maturity.

PMID- 8862792
TI  - Osmotic tolerance limits and properties of murine spermatozoa.
AB  - Osmotic tolerance of spermatozoa is a critical determinant of functional survival
      after cryopreservation. This study first tested the hypothesis that mouse
      spermatozoa behave as linear osmometers, using an electronic particle counter to
      measure the change in sperm volume in response to anisosmotic solutions. The
      resulting Boyle-van't Hoff plot was linear (r2 = 0.99) from 75 to 1200 mOsmolal
      and indicates that 60.7% of the total cell volume is osmotically inactive. Next,
      mouse sperm tolerance to osmotic stress was determined by assessment of plasma
      membrane integrity, mitochondrial viability, and motility. Each functional
      endpoint was measured after exposure to anisosmotic solutions and again after
      return to isosmolality. The dual fluorescent stains-carboxyfluorescein diacetate
      with propidium iodide and Rhodamine 123 with propidium iodide-were used to
      determine membrane integrity and functional mitochondria, respectively. Motility
      was measured by video microscopy in the range of 1-2400 mOsmolal and was further
      analyzed from 140 to 600 mOsmolal using computer-assisted semen analysis. The
      data indicate that motility is substantially more sensitive to osmotic stress
      than either mitochondrial viability or membrane integrity and that mouse
      spermatozoa should be maintained within 76-124% of their isosmotic volume during
      cryopreservation in order to maintain > 80% of pretreatment motility.

PMID- 8862793
TI  - Nonradioisotopic PCR heteroduplex analysis: a rapid, reliable method of detecting
      minor gene mutations.

PMID- 8862794
TI  - Single-tube immuno-capture and PCR of genotoxin-modified DNA: application to gene
      specific damage analysis.

PMID- 8862795
TI  - PCR genotyping of oim mutant mice.

PMID- 8862796
TI  - Prolonged final extension time increases cloning efficiency of PCR products.

PMID- 8862797
TI  - Directional PCR cloning of multiple repeat sequences.

PMID- 8862798
TI  - New approach to mRNA quantification: additive RT-PCR.

PMID- 8862799
TI  - Rapid method for construction of gene disruption plasmids in Saccharomyces
      cerevisiae.

PMID- 8862801
TI  - Chemiluminescent detection of apoptotic DNA: a qualitative and quantitative
      method.

PMID- 8862800
TI  - Site-directed mutagenesis by unique site elimination using filamentous phage
      derived ssDNA templates for plasmids that are resistant to denaturation.

PMID- 8862802
TI  - Single-tube chemical cleavage of mismatch: successive treatment with
      hydroxylamine and osmium tetroxide.

PMID- 8862803
TI  - Optimized filter set and viewing conditions for the S65T mutant of GFP in living
      cells.

PMID- 8862804
TI  - Streamlined protocol for polytene chromosome in situ hybridization.

PMID- 8862805
TI  - Visualization of unstained protein bands on polyvinylidene fluoride membranes
      rehydrated in Tween 20.

PMID- 8862806
TI  - Alternative method for isolation of double-stranded template for DNA sequencing.

PMID- 8862807
TI  - Modification of the acid guanidinium thiocyanate-phenol-chloroform method for
      nuclear RNA isolation.

PMID- 8862808
TI  - Pouring gradients using a cork.

PMID- 8862809
TI  - Quantification of HIV-1 using multiple competitors in a single-tube assay.
AB  - Methods for quantification of human immunodeficiency virus type 1 (HIV-1) based
      on competitive PCR and fragment analysis have been developed. Samples containing
      HIV-1 DNA and known amounts of three cloned competitors were co-amplified by PCR
      with semi-nested primers. The competitor DNAs contained the same long terminal
      repeat primer binding sequences as the wild-type DNA, but they are different in
      internal sequences and length. One of the inner primers was fluorescent-labeled
      to allow discrimination between the wild-type DNA and the three competitors by
      fragment analysis using a standard automated sequencer. A calibration curve using
      the peak area of the three competitors enabled accurate determination of target
      amount with minimal variations. The method presented here can be used for
      quantification of HIV-1 in clinical samples and will be useful for monitoring
      disease progression and treatment effects.

PMID- 8862810
TI  - Vectors encoding alternative antibiotic resistance for use in the yeast two
      hybrid system.
AB  - We have altered the antibiotic resistance of the reporter plasmids and the pJG4-5
      activation-domain and pEG202 DNA binding-domain plasmids used in the Brent
      interaction trap/two-hybrid system. These plasmids were each previously
      ampicillin-resistant, resulting in an inefficient purification of any one plasmid
      from a yeast strain containing all three plasmids that constitute the complete
      interaction trap. By creating derivatives of each of these plasmids expressing
      either kanamycin or chloramphenicol resistance, along with the parent plasmids,
      we now have the option to use the interaction trap in yeast with three E. coli
      differentially selectable vectors. This will allow isolation of any one plasmid
      by purifying all of the interaction trap plasmids from yeast simultaneously and
      plating E. coli transformed with the plasmids onto the appropriate antibiotic
      plate to select the particular plasmid of interest.

PMID- 8862811
TI  - Spectrophotometric quantitation of tissue culture cell number in any medium.
AB  - We have developed a spectrophotometric assay for cell number in suspensions of
      tissue culture cells. For each cell type tested, absorbance between 650 and 800
      nm is linearly dependent upon cell density over a 50-fold range and is
      independent of the color or composition of the medium in which cells are
      suspended. A standard curve of absorbance vs. cell density is used to estimate
      cell number with accuracy and reproducibility superior to hemacytometer counting
      and with speed and ease surpassing use of a Coulter counter. Less than 5000 cells
      are needed for this quantitation. The same cells that are counted can be
      maintained live in culture after the reading is taken, thus allowing the growth
      of cells to be measured within individual cultures over time. The assay should be
      readily extended to assays of cell number directly within microplate culture
      wells. The spectrophotometric assay described here is of significant use in all
      experiments requiring rapid, accurate measurements of cell number, including
      determinations of cell doubling time and equal plating of parallel cultures.

PMID- 8862813
TI  - Quantitative RT-PCR: limits and accuracy.
AB  - In this paper we determine the limits and accuracy of quantitative reverse
      transcription (RT)-PCR using a modification of the original protocol. The
      quantification of mRNA with this procedure requires a preliminary estimation of
      the target molecule (TM) concentration, established from experiments with an
      internal control molecule (ICM). A definitive quantification is then attained
      from serial dilutions of the reverse transcription reaction. The success of this
      latter step is dependent on maintaining an equivalent number of TM and ICM in the
      reaction. The purpose of our study was to evaluate the influence of the deviation
      between the TM and the ICM on the result. We show here that we can control the
      accuracy of the assay by fixing the limit of the TM/ICM ratio. Indeed, when the
      TM/ICM ratio is between 0.66 and 1.5 (i.e., the difference between TM and ICM is
      1.5-fold), the final result has an error of approximately 10%. Exceeding this
      limit produces errors approaching 60%, as in the case of TM/ICM = 2. When the
      above conditions are respected, a difference as small as 20% between two samples
      can be determined with an accuracy of 95%.

PMID- 8862812
TI  - Technical aspects of quantitative competitive PCR.

PMID- 8862814
TI  - Use of flow cytometry and RT-PCR for detecting gene expression by single cells.
AB  - We have developed a method for reliably detecting gene expression by individual,
      phenotypically defined cells. Cells were sorted by flow cytometry into 96-well
      plates containing a Nonidet P-40 (NP40)-based bysis solution. Reverse
      transcription (RT) of cellular major histocompatibility complex class II DQB and
      either bovine leukemia virus (BLV) env or tax/rex mRNA was subsequently conducted
      using gene-specific oligonucleotide primers. Two sequential rounds of PCR were
      then performed to co-amplify DQB and either BLV env or tax/rex cDNA. The PCR
      products were electrophoresed in 6% polyacrylamide gels and visualized by
      ethidium bromide staining. The BLV-infected BL3 cell line was used to establish
      the sensitivity of the method; cellular and viral mRNA were reproducibly detected
      in wells into which single BL3 cells were sorted. Additionally, BLV env mRNA from
      single infected cells was consistently detected in reactions containing as many
      as 1000 uninfected cells. By using this method, 0.012% +/- 0.002% of B cells from
      a BLV-infected cow with persistent lymphocytosis were found to express BLV
      tax/rex mRNA, whereas < or = 0.001% expressed BLV env mRNA. The combination of
      single-cell sorting and RT-PCR provides a powerful new tool to study viral
      transcription, host responses associated with progression of retroviral
      infections or other problems requiring determination of the frequency of cells
      expressing a particular gene(s).

PMID- 8862816
TI  - Measurement of cell adhesion and migration using phosphor-screen autoradiography.
AB  - This study demonstrates the use of phosphor-screen autoradiography as a means of
      measuring cell adhesion and cell expansion on polymer surfaces. The method has
      particular merit in cases where a specific substrate may be opaque or
      biochemically incompatible with colorimetric assay methodologies. With the
      phosphor-screen autoradiography method, there was a linear relationship between
      cell number and quantitated radioactivity. The technique has also been validated
      by comparison with a colorimetric assay of adhesion conducted for attachment to
      conventional culture substrata. The data supported the view that the use of
      phosphor-screen autoradiography was a valid method for detecting cell attachment,
      and it gave equivalent results to the colorimetric assay. Furthermore, a
      comparison between phosphor-screen autoradiography and a dye-staining method
      showed that this technique can be used as a means of quantifying cellular
      expansion over surfaces.

PMID- 8862815
TI  - Detection of calmodulin-binding proteins using a 32P-labeled GST-calmodulin
      fusion protein and a novel renaturation protocol.
AB  - To identify calmodulin-binding proteins in cellular extracts and tissue
      homogenates and to analyze purified calmodulin target proteins, overlay
      procedures using 125I-calmodulin or, more recently, nonradioactive biotinylated
      calmodulin have been widely used. Here we describe a rapid, alternative method
      for detecting calmodulin-binding proteins with a 32P-labeled calmodulin probe
      generated as a glutathione-S-transferase (GST)-fusion protein. We used a modified
      pGEX-2TK vector, which contains the flag epitope and the consensus sequence R-R-A
      S, that can be phosphorylated by the cAMP-dependent protein kinase A. The fusion
      protein is easily purified from bacterial bysates by affinity chromatography
      using glutathione-Sepharose 4B beads. Phosphorylation of GST-calmodulin is
      performed directly on the beads and, after elution with reduced glutathione, the
      labeled calmodulin probe can be used for overlay experiments. We also describe a
      rapid renaturation protocol that enhances the signal for some but not all
      calmodulin-binding proteins and is used after the proteins have been transferred
      to nitrocellulose filters. Furthermore, we have compared the specificity and
      sensitivity of the 32P-labeled GST-calmodulin overlay with those of 125I
      calmodulin and biotinylated calmodulin, clearly indicating that our newly
      developed protocol is a suitable alternative to conventionally used calmodulin
      overlay procedures.

PMID- 8862817
TI  - High-level inducible expression of visual pigments in transfected cells.
AB  - A method for high-level expression of a functionally active, recombinant human
      red cone opsin was developed by adding the coding sequence for the C-terminal
      epitope of bovine rhodopsin onto the C terminus of the cone opsin and cloning the
      resulting construct into the vector pMEP4 beta. The recombinant pMEP4 beta vector
      was transfected stably into 293-EBNA cells, and expression of the cone opsin was
      induced by the addition of CdCl2 into the medium. The recombinant cone opsin was
      reconstituted with 11-cis retinal and purified by immunoaffinity chromatography.
      Spectral analysis prior to and following photobleaching confirmed its identity as
      a red cone opsin. The protein was targeted to the cell membrane and activated
      bovine transducin.

PMID- 8862818
TI  - Direct amplification and cloning of up to 5-kb lentivirus genomes from serum.
AB  - To produce large cDNA strands from biological samples containing limited numbers
      of template molecules, it may be necessary to minimize both nonspecific primer
      attachment in first-strand synthesis and secondary structure in RNA molecules.
      Failure to do so could result in the accumulation of shortened cDNA strands and
      therefore may reduce the yield of large cDNA molecules, sometimes below detection
      level. We show that 5.0-kb cDNA fragments can be generated from simian
      immunodeficiency virus RNA in a specific reverse transcription (RT)-PCR by
      increasing the stringency of the primer-annealing conditions, followed by the
      elimination of excess free primer. Since this method utilizes a relatively long
      primer in the first-strand cDNA synthesis, it is possible to heat-denature the
      nonspecific RNA/primer complexes and RNA secondary structure without dissociating
      the primer from the specific template. In contrast to classic RT assays, in which
      an excess of primer is annealed to denatured RNA just prior to and during reverse
      transcription at relative low temperatures (37 degrees-42 degrees C), this method
      eliminates false priming. To optimize the yield and fidelity of full-length cDNA
      molecules, two PCR amplifications are first performed using both Taq and Pfu
      polymerase, followed by Pfu alone in the second amplification.

PMID- 8862820
TI  - Public science and norms of truthfulness.

PMID- 8862819
TI  - Positive selection of recombinant DNA by CcdB.

PMID- 8862821
TI  - Evolving ethical issues in selection of subjects for clinical research.

PMID- 8862822
TI  - For her own good: protecting (and neglecting) women in research.

PMID- 8862823
TI  - Incompetent persons as research subjects and the ethics of minimal risk.

PMID- 8862824
TI  - Ethical concerns about relapse studies.

PMID- 8862825
TI  - Drug trials, doctors, and developing countries: toward a legal definition of
      informed consent.

PMID- 8862826
TI  - Patient access to experimental drugs and AIDS clinical trial designs: ethical
      issues.

PMID- 8862827
TI  - The ethical problems of the open label extension study.

PMID- 8862829
TI  - Cq sources/bibliography.

PMID- 8862828
TI  - Stanton Glantz on snuffing tobacco research. Interview by Thomasine Kushner.

PMID- 8862830
TI  - What is the proper role for charity in healthcare?

PMID- 8862831
TI  - Reflections on adoption ethics.

PMID- 8862832
TI  - Except in emergencies: AMA ethics and physician autonomy.

PMID- 8862833
TI  - Further exploration of the relationship between medical education and moral
      development.

PMID- 8862834
TI  - Response to "Germ-line therapy to cure mitochondrial disease: protocol and ethics
      of in vitro ovum nuclear transplantation" by Donald S. Rubenstein, David C.
      Thomasma, Eric A. Schon, and Michael J. Zinaman (CQ Vol 4, No 3)
AB  - As a result of the dramatic advances made in molecular biology, gene therapy has
      become viable. The initial endeavors were with monogenetic disorders, but gene
      therapy may also be of benefit in cancer therapy and treatment of infectious
      diseases. The current framework for the ethical discussion of gene therapy is a
      two-dimensional scheme. The first dimension is the target tissue (somatic cells
      versus germ-line cells) and the second dimension is the purpose
      (therapy/prevention versus enhancement). Although the mitochondrial genome occurs
      in eukaryotic cells at several hundred copies and the sequence has been known
      since the late 1980s, it has been excluded from the ethical discussions of gene
      therapy or genetic interventions. With the development of the first IVONT
      protocol and successful experiments with mitochondrial transfection vectors, the
      two-dimensional framework is no longer adequate. Therefore, we propose a three
      dimensional framework for the ethical debate of genetic interventions in humans,
      whereby we include the genome type (nDNA versus mtDNA) as a third dimension. The
      ethical evaluation of all imaginable genetic interventions is located on five
      different levels. The demands for ethical justification are different for each.

PMID- 8862835
TI  - Physician experience as a measure of competency: implications for informed
      consent.

PMID- 8862836
TI  - Second, let no harm be done: an American antiimmigration dilemma.

PMID- 8862837
TI  - Excitation and inhibition in epilepsy.
AB  - The term epileptic seizures is used to describe a variety of paroxysmal signs and
      symptoms resulting from a large number of underlying pathological processes.
      Generalized tonicclonic convulsions, therefore, reflect entirely different basic
      neuronal mechanisms than those of typical absences. Animal research suggests that
      the former result from disturbances that involve disinhibition, whereas the
      abnormality giving rise to the latter requires intact, if not enhanced,
      inhibition in order to sustain hypersynchronous neuronal discharges.
      Investigations in human mesial temporal lobe epilepsy and chronic experimental
      animal models indicate that partial seizures can also reflect multiple underlying
      mechanisms, with some disinhibitory in type, while others appear to be
      hypersynchronous and associated with enhanced inhibition. Just as more than one
      epileptogenic disturbance can result in transition to ictus, it is likely that
      more than one mechanism can be engaged to terminate epileptic seizures, that
      these diverse processes could result in different postictal manifestations, and
      that they could conceivably contribute differently to the development of
      interictal behavioral disturbances. An appreciation for the fact that epilepsy is
      not merely an increase in excitation and/or a decrease in inhibition, but a
      variety of complicated neuronal interactions in different patients, or even at
      different times in the same patient or same seizure, is essential to the
      development of effective treatments to control epileptic seizures and prevent
      their consequences.

PMID- 8862838
TI  - The efficacy of retrograde infusion with LY231617 in a rat middle cerebral artery
      occlusion model.
AB  - BACKGROUND AND PURPOSE: We examined the efficacy of the antioxidant LY231617
      administered five hours following middle cerebral artery (MCA) occlusion in rats.
      METHODS: The treatment was contrived for a two hour interval. Group A (n = 16)
      was left untreated. Group B (n = 16) received an intravenous infusion of
      LY231617. Group C (n = 16) received saline (86 microliters/min) by retrograde
      infusion of the cerebral vein (RICV). Group D (n = 22) was administered LY231617
      (10mg/kg/2 hr) in saline (86 microliters/min) by RICV. Local cerebral blood flow
      with [14C]-iodoantipyrine and blood-brain transfer constant with 14C-alpha-amino
      isobutyric acid were examined. Early ischemic damage was histologically examined
      with cresyl violet and Luxol fast blue and with triphenyl-tetrazolium chloride.
      RESULTS: The results revealed a marked increase in local cerebral blood flow
      (over 600%, p < 0.01) after RICV with LY231617, with a significant improvement of
      BBB permeability in rats from group D. Ischemic brain damage measured with Luxol
      fast blue and triphenyl-tetrazolium chloride methods showed a significant
      improvement (50-91%) of ischemic damage in group D, as compared to groups B and
      C. CONCLUSION: Retrograde infusion of the cerebral vein with LY231617 resulted in
      a significant amelioration at seven hours post MCA occlusion.

PMID- 8862839
TI  - Epidemiological study of reptured intracranial aneurysms in the Saguenay-Lac
      Saint-Jean region (Quebec, Canada).
AB  - BACKGROUND: Using a population-based register of the Saguenay-Lac-Saint-Jean
      region (Quebec, Canada), the genealogical reconstruction of 533 individuals with
      intracranial aneurysm (IA) showed a familial aggregation (the presence of
      aneurysm in two or more first- to third-degree relatives) for 159 (29.8%) of
      them; this proportion is much higher than reported elsewhere. OBJECTIVE: As part
      of an ongoing project to assess a genetic predisposition to intracranial
      aneurysms in the Saguenay-Lac-Saint-Jean population, the objective of the present
      study was to determine whether age-specific rates of reputed cerebral aneurysms
      were higher than in other populations. DESIGN: A retrospective study of cases of
      proven ruptured IAs which were hospitalized during the 1973 to 1992 period was
      conducted. Age-adjusted rates were computed and compared to those reported in the
      Helsinki population. RESULTS: We identified 412 cases of ruptured aneurysms. The
      age-adjusted incidence rate was 7.2/100,000/year (6.2 for men, 8.1 for women),
      which is similar to the incidence rates reported in other studies. Although the
      mean age at time of rupture was younger (46.6 years +/- 13.8) than usually
      reported, no increase in age-specific incidence rates was detected. CONCLUSIONS:
      The results of this epidemiological study neither support nor reject the
      hypothesis of a genetic predisposition to intracranial aneurysms in the Saguenay
      Lac-Saint-Jean population.

PMID- 8862840
TI  - Risk factors for peak dose dyskinesia in 100 levodopa-treated parkinsonian
      patients.
AB  - BACKGROUND: No clinical parameter other than "sufficient" dopamine denervation
      and exposure to exogenous levodopa has been unquestionably linked to dyskinesia
      in levodopa-treated Parkinson's disease patients. METHODS: We retrospectively
      analyzed data on 100 consecutive patients treated with levodopa for 1 to 18 years
      to identify clinical risk factors for dyskinesia. The cumulative dyskinesia-free
      survival probability in relation to levodopa therapy was assessed using the
      Kaplan-Meier method. RESULTS: Overall, 56% of patients developed dyskinesia after
      a mean of 2.9 years, a figure similar to the average duration of levodopa
      treatment in the non-dyskinetic group. Dyskinetic patients were significantly
      younger at disease onset, but their mean latency to dyskinesia induction after
      levodopa initiation was not different from older dyskinetic individuals and the
      overall dyskinesia-free survival of younger subjects was not worse either.
      Dyskinetic patients were on a higher daily levodopa dose than non-dyskinetic
      subjects when dyskinesia emerged, but the cumulative levodopa dose used prior to
      dyskinesia did not discriminate dyskinetic from non-dyskinetic patients. A delay
      in initiating levodopa therapy of more than three years after disease onset and
      levodopa treatment initiation in Hoehn-Yahr stage II compared to stage I patients
      did not increase the probability of developing dyskinesia over time. CONCLUSIONS:
      Since withholding levodopa therapy did not increase the risk for dyskinesia in
      our patients and can delay the emergence of dyskinesia after onset of
      parkinsonian symptom, a trial with a dopaminomimetic agonist as initial treatment
      appears logical.

PMID- 8862842
TI  - Perioperative problems in Parkinson's disease and their management: apomorphine
      with rectal domperidone.
AB  - OBJECTIVE: To present guidelines on the use of apomorphine in combination with
      rectal domperidone in Parkinson's disease (PD) patients undergoing abdominal
      surgery and to review the perioperative problems encountered in such patients.
      BACKGROUND: PD patients undergoing abdominal surgery present a major therapeutic
      challenge. Because most antiparkinsonian medications must be withheld until the
      patient is able to resume oral intake, resulting rigidity and akinesia as well as
      alterations in gastrointestinal motility, respiratory function and swallowing
      mechanisms predispose these patients to numerous serious postoperative
      complications. We have found that parenteral apomorphine in combination with
      rectal domperidone markedly facilitates the care of these difficult patients.
      METHODS: Presentation of two illustrative cases with review of the literature.
      RESULTS: A standardized protocol using subcutaneous apomorphine and rectal
      domperidone was used in two PD patients who underwent abdominal surgery.
      Excellent control of parkinsonian symptomatology was obtained without side
      effects. The simplicity of the protocol was emphasized in our second patient who
      required urgent reoperation; the surgery nursing staff was able to restart the
      apomorphine immediately without having to wait for neurological follow-up
      assessment. CONCLUSIONS: The use of parenteral apomorphine with rectal
      domperidone in the immediate postoperative period for patients unable to take
      oral antiparkinson drugs increases patient comfort, facilitates nursing care and
      may reduce serious postoperative complications.

PMID- 8862841
TI  - Localizing muscles for botulinum toxin treatment of focal hand dystonia.
AB  - BACKGROUND: There is currently no consensus on the best way to localize muscles
      in the forearm for botulinum toxin (BTX) injection. We devised a study to compare
      electromyography (EMG) with local stimulation through a cannula for localizing
      forearm muscles for botulinum toxin (BTX) injection, and for predicting the risk
      of unwanted weakness in non-target muscles. METHODS: In 12 patients with focal
      hand dystonia a single "target" muscle, determined by clinical examination to
      contribute most to the dystonic hand posture, was selected for botulinum toxin
      injection. The patients were randomized into 2 treatment groups, one in which the
      target muscle was localized by recording the EMG signals during voluntary
      contractions (8 patients) and the other in which the target muscle was localized
      by local electrical stimulation (4 patients). The target muscle was then injected
      with a standardized dose of BTX. RESULTS: At follow-up 3 weeks after BTX
      injection the target muscle was weakened in 7/12 patients (4/8 of the EMG group,
      and 3/4 of the stimulation group). Additional noninjected muscles, adjacent to
      the target muscle, were weakened in 5 of these 7 patients, presumably from
      diffusion of the toxin. CONCLUSIONS: Localization by stimulation is probably at
      least as good as EMG. Each technique has certain advantages. Weakness of "non
      target" muscles was not consistently predicted by either EMG or stimulation
      suggesting that BTX diffuses farther than the volume conduction of EMG signals or
      the spread of effective stimulus current.

PMID- 8862843
TI  - Focal midbrain glioma: long term survival in a cohort of 16 patients and the
      implications for management.
AB  - BACKGROUND: Focal gliomas involving the midbrain tectum and tegmentum have been
      identified as having a better prognosis than diffuse tumors affecting the brain
      stem. However, only limited information is available concerning treatment
      effectiveness and long term outcome for these patients. METHODS: A retrospective,
      population-based cancer registry survey was performed to assess the clinical
      features and treatment courses of patients with focal midbrain tumors. RESULTS:
      Sixteen patients with midbrain gliomas were identified; eight had tectal gliomas
      and eight tegmental gliomas. Thirteen patients presented with symptoms related to
      hydrocephalus, and 12 required a ventriculoperitoneal shunt. Seven patients
      underwent surgery directed at the tumor. Eight patients underwent initial
      radiation therapy and none had initial chemotherapy. One patient diagnosed at age
      18 months had a rapidly growing tumor after 14 months of follow up which has
      responded to chemotherapy. The mean survival of this patient population was 84
      months (range 3-280 months) after diagnosis, with only one tumor related death
      occurring (280 months after diagnosis). Survival was not affected by tumor
      location within the midbrain (tegmental or tectal) or by whether radiation
      therapy was or was not administered. CONCLUSIONS: Patients with focal midbrain
      gliomas require symptom control aimed at treatment of hydrocephalus, or mass
      effect from the tumor. However the extended survival of this population suggests
      that routine aggressive surgical debulking is often not required. Furthermore,
      the routine use of radiation therapy or chemotherapy for all such patients is
      questioned.

PMID- 8862844
TI  - Triphasic waves during post-ictal stupor.
AB  - BACKGROUND: The term, "triphasic wave" originally described an EEG pattern
      believed to be a marker for a specific stage of hepatic coma. For 4 decades, the
      diagnostic and prognostic specificity of the pattern remains controversial. Its
      pathophysiology also continues to be elusive. METHODS: EEG recordings were
      obtained in three patients known or suspected to have primary generalized
      epilepsy. In 2 patients, the EEGs were part of long-term monitoring using
      simultaneous video-EEG telemetry. For the third patient, the EEG was secured only
      during the post-ictal unconsciousness. These 3 patients were specifically
      selected because of the presence of triphasic waves in their EEGs. RESULTS:
      Triphasic waves were observed in the EEG of the 3 patients only during post-ictal
      unconsciousness. The pattern was transient, being preceded by generalized
      suppression and delta slow waves and followed by theta activities. Alpha rhythms
      supervened when the patients became fully alert. CONCLUSION: A post-ictal state
      should be considered in unconscious patients with triphasic EEG waves.

PMID- 8862845
TI  - Functional MRI localization of language in a 9-year-old child.
AB  - BACKGROUND: Localizing critical brain functions such as language in children is
      difficult and generally requires invasive techniques. Recently sensory, motor and
      language functions in adults have been mapped to specific brain locations using
      functional imaging techniques. Of these techniques, functional MRI (fMRI) is the
      least invasive and has the highest spatial and temporal resolution. Its use in
      adults is well documented but application to children has not been as well
      described. In the present study lateralization and localization of language was
      evaluated with fMRI prior to epilepsy surgery in a nine-year-old male with
      complex partial seizures, attentional difficulty and decreased verbal
      proficiency. METHODS: Two language paradigms well studied in adults (read, verb
      generation) and two additional language paradigms (antonym generation, latter
      fluency) were studied using whole brain fMRI after stimulus items and timing were
      adjusted to achieve the desired performance level during imaging. The patient was
      also conditioned to the magnet environment prior to imaging. RESULTS: Word
      reading and letter fluency tasks produced lateralized and localized activation
      similar to that seen in adults. The patient had no language deficits following an
      anterior 2/3 dominant temporal lobe resection. CONCLUSIONS: With modifications of
      protocols such as those detailed in this report, this non-invasive method for
      localizing language function is feasible for the presurgical evaluation of
      children as well being applicable for a variety of developmental language issues.

PMID- 8862846
TI  - Listeria spinal cord abscess--clinical and MRI findings.
AB  - BACKGROUND: Intramedullary spinal cord abscess due to Listeria Monocytogenes is
      an uncommon condition usually affecting immunocompromised patients. METHOD: Case
      study. RESULTS: A 69-year-old man presented with 3 weeks history of subacute
      paralysis of both lower limbs and the left upper limb. Myelogram and CT scan
      showed a widened upper cervical cord. CSF revealed lymphocytosis, moderately
      elevated protein and depressed glucose. A gadolinium-enhanced MRI showed diffuse
      cervical cord edema with two ring-enhancing lesions at C2-C3. Blood and CSF
      cultures grew Listeria Monocytogenes. He received IV ampicillin and gentamycin;
      the latter was discontinued after 1 month due to nephrotoxicity. Serial MRI over
      the next 3 months showed significant reduction in the size of these abscesses.
      The patient made a modest improvement in the power of his lower limbs, however he
      remained bed-ridden. Aside from being a mild, diet-controlled diabetic, there was
      no evidence of immunosuppression. CONCLUSION: Listeria spinal cord abscess is a
      treatable disorder and should be considered in the differential diagnosis in
      patients with a subacute onset of spinal cord dysfunction.

PMID- 8862847
TI  - Headache and scalp edema in sickle cell disease.
AB  - BACKGROUND: Major neurological complications of sickle cell disease include
      cerebral infarction and intracranial hemorrhages. METHODS: We describe the case
      of a 25-year-old man with sickle cell disease who developed a severe headache of
      acute onset, located at the vertex. There was associated pitting edema of the
      scalp. RESULTS: Technetium and gallium bone imaging showed focal decreased uptake
      of the tracers, consistent with a recent fronto-parietal skull infarction.
      Management included intravenous hydration and analgesic medication. CONCLUSIONS:
      In addition to the more common intracranail vaso-occlusive complications, skull
      infarction should be considered as a cause of newonset headache in patients with
      sickle cell disease, especially if scalp edema is present.

PMID- 8862848
TI  - Periodontoid synovial cyst causing cervico-medullary compression.
AB  - BACKGROUND: Periodontoid synovial cysts are rare lesions which may produce
      symptomatic cervico-medullary compression. METHOD: We report such a patient,
      whose progressive neurological deterioration required surgical treatment by
      transoral odontoidectomy and decompression. RESULTS: The diagnostic and
      theraputic interventions are described, including a lumbar puncture which
      precipitated a transient loss of consciousness and respiratory arrest. Surgery
      achieved clinical improvement, without complications or need for operative
      stablization. Detailed neuropathology is presented, as well as a literature
      review. CONCLUSION: Appropriate neuroradiological assessment is required in
      patients with suspected cervico-medullary compression, and symptomatic
      periodontoid synovial cysts may respond well to transoral surgical decompression.

PMID- 8862849
TI  - Neurology and the community.

PMID- 8862850
TI  - Re: Isolated supranuclear nerve palsy: a review of nine cases (Can J Neurol Sci
      1995; 22:301-304)

PMID- 8862851
TI  - A participant's observations: preparing DSM-IV.
AB  - OBJECTIVE: To provide an overview of the process of creating the DSM-IV from a
      participant's perspective. METHOD: Narrative review. RESULTS: In its attempt to
      address the perceived weaknesses of both the content and development of the DSM
      III and DSM-III-R, the DSM-IV development was based on commissioned reviews for
      sets of diagnoses, especially designed field trials and a transparent decision
      making process. CONCLUSIONS: Nosology is an ambitious and complicated enterprise.
      Classification systems must evolve as new empirical evidence is presented. Many
      of the obstacles faced by the DSM-IV work groups, therefore, may be moot for
      those formulating DSM-V. The DSM-IV development process was carefully planned,
      and the profession is indebted to the American Psychiatric Association (APA) for
      its initiative and effort in producing this system.

PMID- 8862852
TI  - Effects of nonparental child care on child development: an update.
AB  - OBJECTIVE: To review the published literature on the effects of nonparental and
      out-of-home care on infants, toddlers, and preschoolers. METHOD: Narrative
      literature review. RESULTS: Although substantial controversy persists, the
      accumulated evidence suggests that nonparental care does not necessarily have
      either beneficial or detrimental effects on infants and children, although it can
      have such effects. In some circumstances, careproviders establish relationships
      with children that have significant effects on development, and this increases
      the importance of ensuring that careproviders are well trained, behave
      sensitively, and are stable rather than ephemeral figures in children's lives.
      Nonparental care is associated with behaviour problems (including aggression and
      noncompliance) when the care is of poor quality and opportunities for meaningful
      relationships with stable careproviders are not available, however. CONCLUSION:
      The effects of out-of-home care vary depending on the quality of care as well as
      the characteristics of individual children, including their age, temperaments,
      and individual backgrounds.

PMID- 8862853
TI  - Identifying narcissistic personality disorders in preadolescents.
AB  - OBJECTIVE: To establish whether consensus exists among 3 diagnostic systems that
      outline criteria for narcissistic personality disorders (NPDs) in children
      (Kernberg), in adolescents (Bleiberg), and in adults primarily (DSM-IV) and to
      identify age-related criteria for preadolescents. METHOD: A comparative analysis
      was used to determine the rate of concordance for the 9 DSM-IV criteria for NPD.
      RESULTS: There is a high concordance among the 3 systems for DSM criteria,
      suggesting that NPD can be identified among preadolescents. CONCLUSIONS:
      Preliminary ways of adapting DMS-IV criteria for NPD in this age group are
      discussed.

PMID- 8862854
TI  - Families of children with attention deficit hyperactivity disorder: a review.
AB  - OBJECTIVES: 1) To review the evidence of attention deficit hyperactivity disorder
      (ADHD) and other conditions in family members (siblings and parents) of children
      with ADHD and determine the importance of genetic and environmental factors in
      this condition. 2) To describe the prospective 10-year follow-up of 65 families
      with ADHD children and 43 families of matched normal controls. 3) To review
      various studies that have looked at parent-child interactions with ADHD children
      on and off stimulant medication, and such interactions over time. The paper thus
      provides an overview of family pathology and functioning of families of ADHD
      children over time. METHOD: The paper outlines twin, sibling, family and adoption
      studies with regard to possible genetic and environmental factors in ADHD. It
      also presents data of a prospective 10-year follow-up of 65 families with ADHD
      children and 43 families of normal controls. This family study evaluated
      sociocultural factors, child rearing practices, health of family members and
      relationships, as well as the parental view of the child's functioning over time.
      RESULTS: A review of the literature suggests that ADHD has a strong genetic
      component, but that environmental factors also play an important role. Families
      of children with ADHD have more problems than families of normal controls, but
      these problems improve as the child with ADHD grows up and leaves home. Families
      of ADHD subjects can appreciate positive as well as negative changes in their
      children over time. Generally, family interactions with children with ADHD are
      problematic but improve when the child is on medication and when the child
      becomes an adult. CONCLUSIONS: This condition has strong genetic underpinnings;
      therefore, diagnosing and treating family members (parents and siblings) as well
      as the child with ADHD is important in improving parent-child interactions and
      better long-term outcome for the child and his or her family.

PMID- 8862855
TI  - The use of selective serotonin reuptake inhibitors in young children with
      pervasive developmental disorders: some clinical observations.
AB  - OBJECTIVE: To study the effects of a new group of psychotropic medications, the
      selective serotonin reuptake inhibitors (SSRIs), on some symptoms of young
      children (under 7 years old) with pervasive developmental disorders (PDD).
      METHOD: Open clinical trial. RESULTS: Medications produced positive results in
      half the children, particularly those with obsessional, repetitive, and anxiety
      symptoms. The medication was discontinued in half the children: one-quarter for
      worsening of symptoms and the other quarter for doubtful side effects.
      CONCLUSIONS: SSRIs may have a role to play in ameliorating some symptoms of PDD.
      Further studies with standardized measurements, however, are needed to elucidate
      which children and what symptoms could benefit from which medication.

PMID- 8862856
TI  - A clinical and academic outcome study of children attending a day treatment
      program.
AB  - OBJECTIVE: To assess the behavioural and academic improvement of children who
      attended a day treatment program during a defined period of time. METHOD: Forty
      six children admitted consecutively to the project were assessed on admission and
      discharge using behavioural and academic measures. They also had intelligence and
      language assessments. The subjects attended the program for one academic year, on
      the average. The large majority presented with disruptive behaviour disorders and
      low academic achievement levels. RESULTS: There was a significant improvement
      reported by the parents in externalizing (P < 0.001) and internalizing (P < 0.05)
      behaviour. The subjects also gained one academic year, but their levels continued
      to be low in terms of percentiles. Measures of academic improvement showed
      significant associations with cognitive measures only (subscales of Wechsler
      Intelligence Scale for Children-Revised [WISC-R] and Clinical Evaluation of
      Language Fundamentals-Revised [CELF-R]). CONCLUSION: A day treatment and school
      program is an effective modality for treatment and remediation of children with
      severe psychiatric disorders. The academic underachievement may be resistant to
      remediation within the limited period of attendance in such a program.

PMID- 8862857
TI  - Psychopathology in adolescent mothers and its effects on mother-infant
      interactions: a pilot study.
AB  - OBJECTIVE: This study assessed adolescent maternal psychopathology and its
      relation to the quality of mother-infant interactions. METHOD: Twenty-one mother
      infant pairs recruited from an adolescent medicine clinic were assessed for socio
      demographic background, psychosocial adversity, conduct disorder, alcohol or
      substance dependence, and depression. Dyads were videotaped during free play and
      their interactions rated using the Crittenden Child-Adult Relational Experimental
      (CARE) Index. RESULTS: A large proportion of mothers exhibited psychopathology.
      Severity of maternal depression correlated positively with maternal
      controllingness and infant difficulty. Severity of maternal antisocial history
      correlated positively with maternal unresponsiveness and infant passivity.
      CONCLUSION: Though preliminary, this work suggests that adolescent maternal
      depression and antisocial history have different effects on the quality of mother
      infant interactions. Researchers and clinicians interested in adolescent
      parenting should consider psychopathology as a contributing variable to the
      quality of mother-infant interactions.

PMID- 8862858
TI  - The mental health of children in foster care: a comparison with community and
      clinical samples.
AB  - OBJECTIVE: To determine whether the psychiatric profile of children in foster
      care is more similar to clinical or community profiles. METHOD: Caregiver and
      teacher ratings of DSM-III-R externalizing and internalizing symptoms were
      collected for 3 groups of children: children in foster care, children assessed at
      a children's mental health centre, and a community sample. RESULTS: Children in
      foster care approximated the numbers and types of symptoms of the clinical
      sample. Coming from a family on social assistance, having a parent with a
      criminal history, and being of the male gender were correlated with higher
      externalizing and internalizing symptom scores independent of group membership.
      Group membership accounted for less than 5% of the variance in psychiatric
      symptom scores. CONCLUSIONS: The high symptom burden of children in care is
      substantially attributable to their high-risk histories, and treatment should be
      designed with this in mind.

PMID- 8862859
TI  - Prevention concerning mental health: the adolescent's perspective.
AB  - OBJECTIVE: To examine several subjective components of adolescents' behaviour
      concerning mental illness prevention. METHOD: Adolescents' knowledge, their
      attitudes and subjective norms, as well as their thoughts about how they would
      concretely handle a psychological problem were measured. A self-administered
      questionnaire was completed by 438 male and female adolescents in grades 8 and
      11. RESULTS: Gender and age differences were revealed: girls and older
      adolescents were more attuned to prevention. Further, the influence on young
      people of peers and parents was also apparent. CONCLUSION: Adolescents perceive
      prevention concerning mental health as important.

PMID- 8862860
TI  - Building curriculum for training in community, child psychiatry.
AB  - OBJECTIVE: To present a practical approach to curriculum design for community
      based care in child psychiatry. METHOD: A design template is presented, steps for
      a curriculum review are derived from it, and as an example, a small academic
      division's program is reviewed. RESULTS: The division's curriculum was developed
      according to the template, resulting in an enhanced focus and improved coverage
      of topics through a combination of experiential and didactic teaching.
      CONCLUSION: The suggested format is considered applicable to child psychiatric
      training programs of all sizes and offers an opportunity to review or initiate
      the teaching of community child psychiatry.

PMID- 8862861
TI  - Re: Acute dystonic reaction with risperidone.

PMID- 8862862
TI  - Re: Iron overload and psychiatric illness.

PMID- 8862863
TI  - Victim subculture or the "poor me" syndrome.

PMID- 8862864
TI  - The electroretinogram and neuropsychological functioning in cocaine addicts.

PMID- 8862865
TI  - A philosophy of psychiatry?

PMID- 8862866
TI  - Successful multimodal treatment of a child with selective mutism: a case report.

PMID- 8862867
TI  - Introduction: concepts of antisocial behaviour, of cause, and of genetic
      influences.

PMID- 8862868
TI  - Issues in the search for candidate genes in mice as potential animal models of
      human aggression.
AB  - Conceptual and methodological issues in the search for candidate genes for mouse
      aggression and for the development of animal models of human aggression are
      considered. First, the focus is on genetic and then behavioural aspects of the
      search for candidate genes in mice. For the genetic aspect, two approaches are
      presented. In mice, these are chromosome mapping of polymorphic genes and
      evaluation of gene (polymorphic or monomorphic) function using knockout mutants.
      For the behavioural aspect, several parameters, including the type of aggression,
      measure of aggression, test situation and opponent type can have effects on the
      obtained genetics. This is illustrated for the offence type of attack behaviour
      in mice. The current combination of sophisticated genetic and behavioural
      analyses will result in time in the identification of many of the genes with
      effects on variation and development of one or more types of murine aggression.
      Since mouse and humans have many homologous genes mapped to homologous chromosome
      regions, it is conceivable that individual genes identified for one or more types
      of mouse aggression may be developed as animal models for human aggression.
      Genetic, physiological and behavioural limitations and uses of such models are
      discussed.

PMID- 8862869
TI  - Aggression from a developmental perspective: genes, environments and
      interactions.
AB  - Genetic influences on the social behaviours of non-human mammals are ubiquitous,
      powerful and readily detected. But demonstrations that social behaviours are
      influenced by genes constitute only part of the story. Developmental findings
      have helped complete the picture. Specifically, these studies show that: (1)
      genetic effects for aggressive behaviours are highly malleable over the course of
      development; (2) genetic influences on aggressive behaviour are more dynamic,
      easily achieved and open to rapid manipulation than has been recognized in
      current models of social evolution and behavioural genetics; (3) developmental
      timing has a significant impact upon the nature of the genetic effects observed
      in aggressive behaviours. These empirical results are consistent with the view
      that social behaviours are among the first features to be influenced by genetic
      selection and by environmental experience. Social actions have distinctive
      properties in adaptation because they organize the space between the organism and
      the environment and promote rapid, selective and novel accommodations. The modern
      integrative view of the development of individual-in-context brings attention to
      the correlation between constraints within and external to individuals. This
      paper reviews findings on how these processes become integrated over time in
      individuals and species, and their implications for the nurture of nature.

PMID- 8862870
TI  - A twin study of self-reported criminal behaviour.
AB  - Twin studies can be used to investigate the contributions of genetic factors, the
      common or shared environment, and the unique or non-shared environment to
      individual differences in a measurable characteristic. This paper reports the
      results of preliminary analyses of self-reported data on arrests and criminal
      behaviour from the Vietnam Era Veteran Twin Registry. The subjects for the study
      were 3226 male twin pairs in which both members served in the military during the
      Vietnam era. There were significant influences from both genetic factors and the
      common environment on early arrests. Genetic factors, but not the common
      environment, significantly influenced whether subjects were ever arrested after
      age 15, whether subjects were arrested more than once after age 15, and later
      criminal behaviour. The common environment, but not genetic factors,
      significantly influenced early criminal behaviour. The environment shared by the
      twins has an important influence on criminality while the twins are in that
      environment, but the shared environmental influence does not persist after the
      individual has left that environment. Genes are likely to influence the
      occurrence of criminal behaviour in a probabalistic manner by contributing to
      individual dispositions that make a given individual more or less likely to
      behave in a criminal manner.

PMID- 8862871
TI  - Heterogeneity among juvenile antisocial behaviours: findings from the Virginia
      Twin Study of Adolescent Behavioural Development.
AB  - The examination of heterogeneity in antisocial behaviour was accomplished by
      applying latent class analytic methods to multivariate categorical data on 389
      same-sex male twins, aged 11 to 16 from the Virginia Twin Study of Adolescent
      Behavioural Development (VTSABD). The data included multiple measures of
      oppositional and conduct disorder, attention deficit disorder, hyperactivity,
      impulsivity, reading disability and anxiety from mother, teacher, and child
      report from both questionnaire and interview (child and adult psychiatric
      assessment; CAPA). A latent four-class model provided a good fit to the data and
      yielded four phenotypically and aetiologically distinct latent classes: (1) a non
      symptomatic class influenced by both additive genetic and shared environmental
      factors; (2) a hyperactivity-conduct disturbance class accounted for by both
      additive and non-additive genetic effects; (3) a 'pure' conduct disturbance class
      with a very strong shared environmental component; and (4) a multisymptomatic
      class explained entirely by the additive effect of the genes. Further
      characterization of these four latent classes by age of the child and parental
      psychiatric history is also shown.

PMID- 8862872
TI  - Predisposition to criminality: Swedish adoption studies in retrospect.
AB  - The predisposition to criminality was studied in 913 women and 862 men from the
      Stockholm Adoption Study. Different genetic and environmental antecedents
      influenced the development of criminality, depending on whether or not there was
      associated alcohol abuse. Male alcoholic criminals often committed repeated
      violent offences, whereas non-alcoholic criminals characteristically committed a
      small number of petty property crimes. These non-alcoholic petty criminals more
      often had biological fathers with histories of petty crime but no excess of
      alcohol abuse. The risk of criminality in alcohol abusers was correlated with the
      severity of their own alcohol abuse, but not with criminality in their biological
      or adoptive parents. Most explained variation in petty crime was due to
      differences between the genetic predispositions of the adoptees, but substantial
      contributions were also made by postnatal environment, either alone or in
      combination with specific genetic subtypes. There was no overlap between the
      congenital antecedents of alcoholism and non-alcoholic criminality, but some
      postnatal variables were common to this kind of criminality and type 2 or male
      limited alcoholism. Low social status alone was not sufficient to lead to petty
      criminality, but did increase risk in combination with specific types of genetic
      predisposition. Unstable preadoptive placement contributed to the risks of both
      petty criminality and male-limited alcoholism.

PMID- 8862873
TI  - Assessing the role of genetics in crime using adoption cohorts.
AB  - The role of genetics in criminal behaviour can be assessed through family, twin
      and adoption studies. This paper discusses the major findings of adoption studies
      that have focused on criminal outcome. Results from adoption studies have
      consistently revealed a relationship between biological parent criminal behaviour
      and adoptee criminal outcome. This finding has been noted in the case of property
      crime, but not in the case of violent crime. Violent crime in adopted-away
      offspring is not related to violent crime in biological parents. Findings from
      the Danish Adoption Cohort suggest that violent crime may be genetically related
      to other types of behavioural deviance. In the Danish Adoption Cohort, there is
      an increased rate of schizophrenia in the adopted-away offspring of biological
      fathers who are convicted of violent crimes. This father violence-adoptee
      schizophrenia relationship cannot be accounted for by the potential confounding
      factors of rearing social status, age at transfer, knowledge of family history of
      crime, or biological parents' mental illness.

PMID- 8862874
TI  - Direct analysis of candidate genes in impulsive behaviours.
AB  - Antisocial behaviour is both heterogeneous and the product of interacting genetic
      and environmental factors acting at different levels of causation. Heritability
      studies show that individual differences in predisposition to antisocial
      behaviour are transmitted vertically in families by genetic mechanisms. Owing to
      aetiological heterogeneity and complexity, study of a variety of other
      behavioural phenotypes may shed more light on the antecedents of antisocial
      behaviour than direct studies on antisocial behaviour. Identification of genetic
      vulnerability factors would clarify mechanisms of vulnerability and the role of
      the environment. Direct gene analysis and genetic linkage analysis have
      identified structural variants in genes involved in neurotransmitter function,
      and some progress has been made towards relating these genetic variants to
      antisocial personality and other behaviours. Thyroid hormone receptor variants
      can cause attention deficit/hyperactivity disorder, and a monoamine oxidase A
      variant leads to aggressive behaviour in one family. Direct gene analyses have
      revealed non-conservative amino acid substitutions and structural variants
      (generally rare) at DRD2, DRD3 and DRD4 dopamine receptors and 5-HT1A, 5-HT2A, 5
      HT2C and 5-HT7 serotonin receptors. The stage is set to identify the phenotypic
      significance of these as well as genetic variants at other loci which may be
      relevant as candidate genes for antisocial behaviour and related behavioural
      differences.

PMID- 8862875
TI  - MAOA deficiency and abnormal behaviour: perspectives on an association.
AB  - We have recently described an association between abnormal behaviour and
      monoamine oxidase A (MAOA) deficiency in several males from a single large Dutch
      kindred. Affected males differed from unaffected males by borderline mental
      retardation and increased impulsive behaviour (aggressive behaviour, abnormal
      sexual behaviour and arson). Nevertheless, a specific psychiatric diagnosis was
      not made in four affected males who had psychiatric examination. Since MAOA
      deficiency raises 5-hydroxytryptamine (5-HT) levels, it provides an interesting
      exception to the low 5-HT paradigm of impulsive aggression. Even if the possible
      relationship between MAOA deficiency and abnormal behaviour is confirmed in other
      kindreds, the data do not support the hypothesis that MAOA constitutes an
      "aggression gene'. In fact, because genes are essentially simple and behaviour is
      by definition complex, a direct causal relationship between a single gene and a
      specific behaviour is highly unlikely. In the case of MAOA deficiency, some of
      the complexities are illustrated by the variability in the behavioural phenotype,
      as well as by the highly complex effects of MAOA deficiency on neurotransmitter
      function. Thus, the concept of a gene that directly encodes behaviour is
      unrealistic.

PMID- 8862876
TI  - Serotonin in alcoholic violent offenders.
AB  - Finnish alcoholic, impulsive, habitually violent offenders have been found to
      have low brain serotonin (5-hydroxytryptamine; 5-HT) turnover which is associated
      with impaired impulse control, a history of suicide attempts, hypoglycaemic
      tendency after an oral glucose load and diurnal activity rhythm dysregulation or
      hyperactivity. Relatively high cerebrospinal fluid (CSF) free testosterone
      concentration is a further characteristic of the offenders with antisocial
      personality disorder. The impulsive offenders may represent a behaviourally
      extreme group of type 2 alcoholics as defined by Cloninger. A large cohort of 800
      subjects, including alcoholic violent offenders, their relatives and male
      controls, has now been gathered from Finland with support from the National
      Institute on Alcohol Abuse and Alcoholism. About 200 subjects have provided CSF
      samples. Leukocytes from the whole cohort have been harvested and immortalized.
      Genes regulating 5-HT functions are now being systematically analysed from these
      samples. Thus far, polymorphisms of the tryptophan hydroxylase (TPH) and 5-HT2C
      receptor genes have been the most informative findings.

PMID- 8862877
TI  - Evolutionary adaptationism: another biological approach to criminal and
      antisocial behaviour.
AB  - Although in a sense "genetic', the conceptual framework of evolutionary
      psychology, behavioural ecology and sociobiology is distinct from that of
      behaviour genetics. Considerable confusion has resulted from failures to
      recognize the distinctions. These disciplines are primarily concerned with the
      characterization of evolved adaptations, which are usually species-typical and
      environmentally contingent, so theory and research in these fields mainly
      concerns environmental rather than genetic sources of behavioural variation.
      Heritable behavioural variation is in general neither predicted by nor supportive
      of adaptationist theories. One might even say that substantial heritability of an
      apparently consequential attribute is a datum that challenges the tenets of
      adaptationism. Behaviour genetics and evolutionary adaptationism have had only
      limited mutual influence, but increasing knowledge of the processes by which
      genotypes affect behavioural phenotypes should facilitate development of a more
      synthetic approach.

PMID- 8862878
TI  - Chronic problems in understanding tribal violence and warfare.
AB  - This paper discusses problems confronting researchers whose work addresses the
      nature, causes and functions of violence and warfare in contemporary tribal
      societies and the interpretation of evidence on these topics from archaeological
      records. A major problem is the paucity of reliable ethnographic evidence
      describing conflicts, causes of conflicts and numbers of casualties suffered.
      There are few first-hand studies of warring tribesmen and little uniformity in
      data collection methods or specific topics covered by the studies. A second
      problem is the wide range of theoretical opinion on ultimate versus proximate
      causes of conflict and often polemic insistence that some causes cannot even be
      admitted into the explanatory framework, as illustrated by the debate between
      cultural materialists and evolutionary anthropologists. A third problem is the
      widespread belief that pre-colonial conflict and warfare was either rare or did
      not exist at all and that where contemporary tribesmen are found to be in lethal
      contests this has been provoked by contact with European colonial expansion.
      Finally, a new problem is emerging: ethnographic descriptions of violence in
      tribal societies are increasingly opposed by politically correct academics who
      argue that it is detrimental to the goals of advocates of native cultural
      survival. The paper concludes with a summary of some of the main features of
      Yanomamo violence and warfare, based on the author's field research and
      publications up to 1990, and introduces new data and theoretical issues that are
      emerging from his most recent field studies since 1990.

PMID- 8862879
TI  - The implications for responsibility of possible genetic factors in the
      explanation of violence.
AB  - Genetic determinism is unlikely to be true of most human behaviour. The discovery
      of a genetically based disposition to violent behaviour would not automatically
      undermine a person's responsibility for such behaviour. The relevant question is
      not just whether the genetic disposition plays a causal role, but whether it is
      so strong as to be irresistible. This requires complex evaluation of different
      kinds of evidence. When genetic causes are combined with others, including
      environmental ones, the resulting picture of human behaviour may be a more
      determinist one than we are used to. Such a picture, if it came to be accepted,
      would not necessarily undermine responsibility. The everyday distinctions between
      what we can and cannot do would still survive. But understanding the full
      implications of such a picture would in some ways modify our attitudes and
      practices. Blame would take a different form, and retributive punishment might
      come to seen unacceptable.

PMID- 8862880
TI  - Legal implications of genetics and crime research.
AB  - Two controversial topics dominate discussions of the legal implications of
      genetics and crime research; (1) the viability and politics of such research,
      which has sparked fervent debate in the USA; and (2) the current status of new or
      atypical criminal law defences, which would include a genetic-defect defence to
      criminal behaviour. This chapter begins by examining the scientifically
      discredited XYY chromosome syndrome defence, the major genetic-defect defence
      that defendants have attempted, albeit unsuccessfully. It then focuses on
      attorneys' efforts to test for evidence of genetic abnormality in the recent and
      highly publicized case involving convicted murderer Stephen Mobley, whose family
      history reveals four generations of violent, aggressive and behaviourally
      disordered men and women. Mobley is currently appealing his death sentence before
      the Georgia Supreme Court on the basis that the trial court denied his request
      both to have genetic testing performed and to have such testing allowed as
      evidence into court. This chapter concludes by emphasizing that the question is
      not whether genetic evidence will ever be admitted into court, but when and under
      what kinds of circumstances. No doubt, genetic evidence, and comparable kinds of
      biological evidence, will have a major impact on juries when such evidence is
      more fully accepted by the legal and scientific communities.

PMID- 8862881
TI  - Ultrasound of the placenta.

PMID- 8862882
TI  - Postpartum examination of the placenta.
AB  - Placental morphologic examination can provide the clinician much information
      regarding pathogenesis in many problems of pregnancy and newborns. This depends
      on appropriate examination at the time of delivery, with triage to pathology
      based on clinical criteria and initial gross examination. The delivery room
      examination can readily assess gross lesions of the cord, villous tissue, and
      membranous surfaces. The chorionicity of multiple gestations can be quickly
      determined. Most microscopic lesions are suggested by the gross examination.

PMID- 8862883
TI  - Clinicopathologic implications of placental pathology.

PMID- 8862884
TI  - The umbilical cord: obstetrically important lesions.

PMID- 8862885
TI  - Placental causes of fetal malformation.

PMID- 8862886
TI  - Surgery of the placenta and umbilical cord.

PMID- 8862887
TI  - Update on endometrial cancer. Introduction.

PMID- 8862888
TI  - Tamoxifen and endometrial neoplasia.

PMID- 8862889
TI  - Role of transvaginal sonography in the evaluation of endometrial hyperplasia and
      cancer.

PMID- 8862891
TI  - Laparoscopic staging of endometrial cancer.

PMID- 8862890
TI  - Surgical staging endometrial cancer.
AB  - Nothing improves the subsequent care of a woman with endometrial cancer more than
      the accurate determination of the extent of her disease. A significant number of
      women whose malignancy is apparently confined to the uterus will have
      extrauterine disease after careful, complete surgical staging. The failure to
      detect and effectively treat unrecognized metastatic disease can have fatal
      consequences; the decision to prescribe potentially harmful therapy to women who
      do not have metastatic disease also has deleterious effects. Although the optimal
      surgical management of any patient must be individualized, careful and complete
      surgical staging at the time of hysterectomy offers the most complete data for
      future management.

PMID- 8862892
TI  - Endometrial papillary serous carcinoma: patterns of spread and treatment.
AB  - Uterine papillary serous carcinoma exemplifies the potential for Mullerian
      epithelium at any site to differentiate along histologic patterns that replicate
      Mullerian epithelium at other sites, especially when neoplastic. Papillary serous
      differentiation is most commonly associated with epithelial ovarian carcinoma.
      Papillary serous differentiation of endometrial malignancy is associated with a
      poor prognosis wrought mainly through the tendency to present as late- stage
      disease. There is a considerable discrepancy between clinical and surgical
      staging. Because surgical stage is the single most important prognostic factor,
      the need for standardized, accurate, and comprehensive staging is highlighted,
      particularly where experimental protocols are being evaluated. Similarly, there
      is a need for strict adherence to standardized histologic criteria and reporting,
      particularly in making the often subtle distinction between papillary
      endometrioid adenocarcinoma and UPSC. Because even the earliest stage of disease
      is associated with a poor prognosis, a case can be made for offering adjuvant
      therapy to all patients diagnosed with UPSC. No single adjuvant modality has
      emerged as preeminent. There is comparable response to both radiotherapy and
      chemotherapy regimens, suggesting a need to compare these regimens in a
      multicenter, randomized trial. Because UPSC constitutes up to 10% of all
      endometrial carcinomas, there should be no difficulty accruing sufficient numbers
      for meaningful analysis. Although such a study may provide clues to optimizing
      available adjuvant strategies, further improvement in treatment regimens is
      required to effectively alter the poor prognosis associated with this condition.

PMID- 8862893
TI  - Endometrial neoplasia: prognostic significance of ploidy status.
AB  - For several decades, clinical and histologic assessment of various phenotypic
      properties has provided a basis for treatment planning. However, it is recognized
      that, preoperatively, clinical assessment identifies only 20% of patients with
      advanced disease. Furthermore, the variability in intraoperative sampling, the
      subjectivity and limitations of histologic interpretation, and the variability in
      response to standardized treatment modalities represent concerns associated with
      the current treatment of endometrial carcinoma. Presumably, early dissemination,
      early recurrence, treatment refractoriness and, ultimately, compromised survival
      are reflections of the inherent biologic characteristics of the tumor. A
      reasonable assumption is that proscribed molecular events determine various
      behavioral characteristics of tumors that become manifested at the time of
      transformation rather than evolving as the tumor volume increases. Therefore, the
      identification of one or more of these quantifiable molecular variables that
      directly or indirectly assess tumor biology would assist clinicians in
      determining patient risk status and in selecting treatment options. As noted, DNA
      ploidy is an independent, broadly applicable, quantifiable predictor of
      progression-free survival in patients with endometrial cancer and, therefore,
      warrants designation as a major prognostic factor or therapeutic determinant.
      Aneuploidy implies the presence of an abnormal quantity of genomic material and
      imparts a progressively less favorable prognosis as the DNA index increases.
      These assayable aberrancies of cellular DNA content presumably reflect the more
      extreme alterations at the molecular level. Because neoplastic transformation is
      generally a multistep process, aberrations in several proto-oncogenes or tumor
      suppressor genes (or both) presumably must be realized before a clinical
      malignancy develops. A number of genes that encode for various regulatory
      proteins are overexpressed in endometrial cancer. Whether these aberrancies are
      fundamental to the pathogenesis of this disease process is unclear. Nevertheless,
      there appears to be an association between DNA ploidy and the overexpression of
      several regulatory genes, such as c-fms, K-ras, HER-2/neu, and p53. Although
      overexpression of these oncogenes and tumor suppressor genes harbor prognostic
      significance in endometrial cancer, the ploidy status of the tumor appears to
      represent the most cogent objective variable. As the etiopathogenesis of
      endometrial carcinoma becomes more discernible, one can envision a limited number
      of tissue-specific molecular-genetic indices characterizing the risk status of
      patients. Because the estimated number of deaths from endometrial cancer has
      doubled since 1987, reassessing of the therapeutic determinants for this disease
      process is important. The management objective for endometrial cancer by the turn
      of the century should be the identification of patients at high risk for advanced
      disease or post-treatment recurrences (or both) at the time of clinical
      declaration of symptoms and diagnosis. Such pretreatment identification would
      afford patients at high risk for advanced or recurrent disease access to
      physicians with special expertise and would facilitate the evaluation and
      application of new or modified therapeutic modalities. Equally important would be
      the identification of patients at low risk for untoward outcome, thereby avoiding
      the cost and morbidity of excessive therapeutic measures.

PMID- 8862894
TI  - The molecular biology of endometrial adenocarcinoma.

PMID- 8862895
TI  - Chemotherapy as adjuvant and salvage treatment in women with endometrial
      carcinoma.

PMID- 8862896
TI  - Modern techniques of radiation therapy for endometrial cancer.

PMID- 8862897
TI  - Special considerations in the treatment of seasonal allergic rhinitis in
      adolescents: the role of antihistamine therapy.
AB  - The symptoms of seasonal allergic rhinitis often develop during adolescence. Teen
      age students with seasonal allergic rhinitis may experience decreased academic
      performance and productivity from the disease or because of the sedative effects
      of some antihistamines. The pharmacologic effects of nonsedating second
      generation antihistamines are compared with those of classical antihistamines.
      The effects of antihistamines on sedation and motor and cognitive function are
      discussed. The role of antiinflammatory agents, decongestants, and combination
      products is reviewed. Potential drug interactions must be considered along with
      factors such as drug-induced weight gain and the use of antihistamines in
      potentially pregnant patients in selecting appropriate antihistamine therapy for
      adolescent patients.

PMID- 8862898
TI  - Mastoiditis in children.
AB  - Fifty-seven children were seen over a 10-year period, 1984-1994, at two large
      pediatric referral centers with a diagnosis of mastoiditis. Twelve had acute
      infection and 45 had chronic manifestations. Clinical presentations and recovered
      bacterial pathogens were identical to those reported in earlier literature
      although the incidence of both acute and chronic mastoiditis has decreased
      markedly since 1950. The availability of computed tomographic (CT) scans during
      this decade has improved the management of chronic disease by defining the
      location of cholesteatomas and the extent of disease as well as possible anatomic
      variations and potential complications encountered during surgery. CT scanning is
      indicated in acute disease when there is suspicion of chronic suppuration or
      destruction of the mastoid.

PMID- 8862899
TI  - Pyomyositis: report of three patients and review of the literature.
AB  - Pyomyositis is the primary infection of skeletal muscles, accompanied by abscess
      formation in the suppurative phase but may be without a focal fluid collection in
      the presuppurative phase. We describe three patients, one with insulin-dependent
      diabetes mellitus, another with sickle cell disease, and the third a previously
      healthy child with varicella infection who developed pyomyositis. Ultrasound or
      magnetic resonance imaging suggested the diagnosis in each case. The patients
      were treated with intravenous antibiotic therapy and two required abscess
      drainage. The infection in the third resolved without surgical drainage. None of
      our patients had residual functional limitations. We believe that a high index of
      suspicion and prompt diagnosis can prevent complications from pyomyositis.

PMID- 8862900
TI  - Slipping rib syndrome as a cause of chest pain in children.
AB  - Four patients with the slipping rib syndrome presenting as chest pain are
      described, and the appropriate literature is reviewed. In two of the patients the
      physicians caring for the children were initially concerned that a cardiac
      condition was the cause of the chest pain, and a cardiac evaluation was done. In
      one patient an emotional cause for the pain was first considered and then a
      cardiac cause was pursued. In the last patient esophagitis was thought to be the
      cause and the child was referred to a gastroenterologist. It is suggested that
      slipping rib syndrome should be considered by physicians when evaluating children
      with a complaint of chest pain. The condition can be easily diagnosed on physical
      examination and therefore may save some patients from an unnecessary cardiac or
      gastroentestinal evaluation.

PMID- 8862901
TI  - Relapsing bacteremia with highly penicillin-resistant pneumococci in a normal
      host.

PMID- 8862902
TI  - Chronic compulsive foot rubbing.

PMID- 8862903
TI  - Chylous ascites associated with gastroschisis.

PMID- 8862904
TI  - Cough-induced Mallory-Weiss tear in a child.

PMID- 8862905
TI  - Dermal injury following the use of fiberoptic phototherapy in an extremely
      premature infant.

PMID- 8862906
TI  - Bezoar in a preterm baby associated with sucralfate.

PMID- 8862907
TI  - Psychological factors in encopresis: comparison of patients to nonsymptomatic
      siblings.

PMID- 8862908
TI  - Keratin biochemistry.

PMID- 8862909
TI  - Basement membrane zone.

PMID- 8862910
TI  - Cytokines.

PMID- 8862911
TI  - Use of vaccines in treatment of malignant melanoma.

PMID- 8862912
TI  - Role of reactive oxygen species in dermatologic diseases.

PMID- 8862913
TI  - Biochemical aspects of psoralen photochemotherapy.

PMID- 8862914
TI  - Hyperlipidemias.

PMID- 8862915
TI  - The porphyrias.

PMID- 8862916
TI  - Nutrition and the skin.

PMID- 8862917
TI  - Cytochrome P-450-dependent drug metabolism in skin.

PMID- 8862918
TI  - Prediction of refractive outcome in penetrating keratoplasty for keratoconus.
AB  - We carried out a retrospective study to evaluate the relationship between
      vitreous cavity length, graft size, and final spherical equivalent refraction
      after penetrating keratoplasty (PK) for keratoconus. We found a straight-line
      relationship between vitreous cavity length and spherical equivalent for a one
      surgeon series using the same technique throughout. The use of 0.25-mm undersized
      grafts shifted the results an average of 2.2 Dioptres in a more hypermetropic
      direction (p = 0.07 for the whole group, p < 0.01 for paired eyes). Hence the
      final spherical equivalent following PK for keratoconus can be predicted. Also,
      by altering the size of the donor graft button, the final refraction can be
      manipulated to some extent towards acceptable ametropia or to match the
      refraction of the fellow eye.

PMID- 8862919
TI  - Herpes zoster peripheral ulcerative keratitis in patients with the acquired
      immunodeficiency syndrome.
AB  - The purpose of this study was to describe the clinical characteristics and course
      of peripheral ulcerative keratitis (PUK) secondary to herpes varicella-zoster
      virus in patients with the acquired immunodeficiency syndrome (AIDS). Three AIDS
      patients with ocular herpes zoster infection (mean age at onset, 33.0 years;
      range, 30-42) developed PUK. The three patients had skin involvement, and two of
      them had bilateral keratouveitis. All were treated with high-dose oral acyclovir
      (4 g/day) with or without topical antiviral therapy. Two of the patients
      responded well to oral acyclovir, but one of them stopped the treatment, and
      bilateral progressive outer retinal necrosis and lethal encephalitis developed.
      The third patient had a recurrent episode of inflammation with PUK, extensive
      stromal scarring, and deep neovascularization. AIDS patients with herpes
      varicella-zoster virus infection may have severe and protracted corneal
      manifestations, including PUK. The correct diagnosis and aggressive early long
      term systemic antiviral treatment must be instituted to control inflammation,
      ulcer progression, and complications.

PMID- 8862920
TI  - Donor factors associated with epithelial defects after penetrating keratoplasty.
AB  - The records of 39 patients undergoing 40 consecutive penetrating keratoplasties
      were reviewed to identify donor factors that might correlate with the presence of
      an epithelial defect on the first postoperative day. Of the 40 transplanted
      corneas, 13 (32.5%) had no epithelial defect, 18 (45%) had some epithelial
      defect, and nine (22.5%) had a total epithelial defect 1 day postoperatively. The
      status of the epithelium was correlated with several donor factors. The only
      factor that had a statistically significant association with the degree of
      epithelial defect was the time interval from preservation to surgery (p = .001).
      Based on a logistic regression model, the probability of having an epithelial
      defect 1 day after penetrating keratoplasty increased with respect to longer
      storage times. These results may aid the surgeon in the selection of donor
      tissue, particularly when performing penetrating keratoplasty on patients with
      ocular surface disorders.

PMID- 8862921
TI  - Recurrent keratopathy after penetrating keratoplasty for aniridia.
AB  - Corneal lesions in aniridia include peripheral pannus and epithelial
      abnormalities that may advance centrally, resulting in the need for penetrating
      keratoplasty. Three patients with aniridia who underwent repeated corneal
      surgical procedures (one keratectomy and six penetrating keratoplasties) are
      described herein. A clinicopathological correlation was performed. In all three
      patients there was evidence of recurrent pannus and epitheliopathy on
      histopathological examination, which correlates with the clinical findings. These
      findings suggest that the pathophysiology of recurrent aniridia keratopathy may
      be related to a primary abnormality in the stem cells of the recipient corneal
      limbus. Aniridic pannus and epitheliopathy recur in grafts after penetrating
      keratoplasty and threaten the transplanted cornea. The risk of recurrent
      keratopathy should be considered when recommending a surgical procedure to
      patients with aniridia.

PMID- 8862922
TI  - Forceps and vacuum injuries to the cornea: histopathologic features of twelve
      cases and review of the literature.
AB  - Histopathologic and ultrastructural features were examined from 11 cases of
      corneal injury from obstetrical forceps and one case from vacuum extraction. Four
      major types of histopathologic features were observed. Type I (n = 4) included
      large tears of Descemet's membrane with a fragment of Descemet's membrane
      extending into the anterior chamber at one end of the tear and scroll formation
      at the other end. Type II (n = 6) consisted of scrolls of Descemet's membrane at
      each margin of the original break. Type III (n = 2) included those with small
      breaks in Descemet's membrane and healing by fibrosis at and posterior to the
      original tear. Type IV (n = 1) contained a small break in Descemet's membrane
      with minimal fibrosis. Transmission electron microscopy revealed Descemet's
      scrolls and retrocorneal fibrous tissue. Scanning electron microscopy revealed
      folds in Descemet's membrane and attenuation or absence of endothelium. Spindle-
      and stellate-shaped cells and pigment granules were present in the area of the
      tear in most cases. A review of the literature is presented.

PMID- 8862923
TI  - Keratoconus and tapetoretinal degeneration.
AB  - In a series of 233 keratoconus cases, electroretinograms (ERGs) and visual evoked
      responses (VERs) were recorded; the results of this study are discussed. In six
      cases, the ERGs were extinguished, and the VERs were pathologic. In contrast to
      this, in four cases, ERGs were normal, but VERs were pathologic. Postoperatively
      the electrophysiologic findings remained the same, and the ophthalmoscopic
      examination of the eyes revealed the existence of a diffuse tapetoretinal
      degeneration or a macular lesion. These data show clearly the coexistence in many
      cases of keratoconus with diffuse tapetoretinal degeneration or macular lesion.
      The preoperative value of an electrophysiologic study of keratoconus patients is
      justified to avoid an unneeded corneal transplant.

PMID- 8862924
TI  - Keratitis in methamphetamine abusers.
AB  - We report four cases of severe corneal ulceration in methamphetamine abusers.
      Methamphetamine abuse has been increasing in California and may exceed cocaine
      abuse in some regions. Methamphetamine's extensive physiologic effects,
      inconsistent street purity, and multiple routes of administration offer many
      possibilities for injury to the cornea. Potential causes of methamphetamine
      related keratitis can be divided into four categories resulting from (a) direct
      pharmacologic and physical effects of methamphetamine; (b) the toxic effects of
      diluting or "cutting" agents such as lidocaine and quinine; (c) effects related
      to the route of drug administration (intravenous, inhalation, smoking); and (d)
      manufacture-related effects of exposure to unintentional caustic contaminants in
      the final product. The increasing prevalence of methamphetamine abuse and the
      severity of the associated ulcers should alert ophthalmologists to the problem of
      methamphetamine-related keratitis.

PMID- 8862925
TI  - Repair of Descemet's membrane detachment with intracameral injection of 20%
      sulfur hexafluoride gas.
AB  - Detachment of Descemet's membrane is a rare complication of cataract surgery that
      can cause permanent corneal decompensation. We report five patients with
      Descemet's membrane detachments who were successfully treated with intracameral
      injection of 20% sulfur hexafluoride gas with resultant resolution of their
      corneal edema.

PMID- 8862926
TI  - Cleavage of human corneal type VI collagen alpha 3 chain by matrix
      metalloproteinase-2.
AB  - The human cornea contains significant amounts of type VI collagen and matrix
      metalloproteinase-2 (MMP-2), but there has been no established relation between
      these two components. The objective of this study was to determine whether
      corneal type VI collagen was susceptible to digestion by MMP-2. Human corneas
      were frozen and then pulverized in liquid nitrogen. The type VI collagen was
      isolated by sequential extractions with sodium chloride buffer, guanidinium
      chloride solution, and guanidinium chloride/dithiothreitol solution.
      Visualization of type VI collagen alpha 3(VI) chain was made by using Western
      blots with specific monoclonal antibodies. The extracts were incubated up to 24 h
      with isolated, activated MMP-2. Within 4 h of incubation, two lower molecular
      weight bands (approximately 190 and 170 kDa) appeared. These bands increased in
      intensity with time but were not further digested into smaller fragments. This
      cleavage activity was inhibited by ethylenediaminetetraacetic acid (EDTA).
      Because type VI collagen represents approximately 25% of the corneal dry weight,
      its degradation properties may be important for the integrity of the stroma in
      scarring episodes and corneal diseases, such as keratoconus.

PMID- 8862927
TI  - A comparison of recurrent and primary herpes simplex keratitis in NIH inbred
      mice.
AB  - Herpes simplex virus (HSV) infection is one of the leading causes of corneal
      blindness. This study compared the clinical, virologic, and immunopathologic
      features of primary and recurrent murine models of herpes simplex keratitis (HSK)
      in the National Institutes of Health (NIH) inbred mouse strain. Primary infection
      resulted in multiple epithelial dendrites, followed by diffuse stromal
      opacification, symptoms that do not mimic what is seen in human HSK. In contrast,
      recurrent infection presented clinical features that included microdendrites,
      focal stromal opacities, disciform endotheliitis, and corneal neovascularization,
      which were similar to those observed in human disease. Immunohistochemical
      characterizations indicated that the number and duration of T cells and
      macrophages in recurrent HSK resemble those observed in primary disease. Results
      also indicated that the amount of infectious virus detected in the cornea during
      primary and recurrent disease was similar. However, when corneas were stained for
      HSV-1 antigens, mice with primary HSK displayed diffuse HSV antigen expression
      throughout the cornea, whereas HSV antigens were more focally distributed in
      recurrent disease. These data suggest that the clinical differences between the
      recurrent and primary herpetic keratitis may, in part, reflect the different
      distribution of HSV-1 antigens within the cornea.

PMID- 8862928
TI  - Induction of alpha-smooth muscle actin expression and myofibroblast
      transformation in cultured corneal keratocytes.
AB  - The effects of serum, transforming growth factor (TGF) beta 1, bFGF, and heparin
      on in vitro myofibroblast transformation was studied. Primary rabbit corneal
      keratocytes were grown under serum-free conditions or in media supplemented with
      serum (10% fetal calf serum), TGF beta 1 (0.1-10 ng/ml), basic fibroblast growth
      factor (bFGF) (0.1-10 ng/ml), or heparin (10 U/ml). Cells were analyzed for
      expression of alpha-smooth muscle actin (alpha-SM actin), alpha 5 beta 1 integrin
      (the high-affinity fibronectin receptor) and fibronectin by immunoprecipitation,
      Western blotting, and immunofluorescence. Corneal keratocytes grown in the
      presence of serum showed a typical fibroblast morphology with induction of alpha
      SM actin expression in 1 to 10% of cells. Addition of bFGF blocked serum-induced
      alpha-SM actin expression, whereas addition of TGF beta 1 enhanced alpha-SM actin
      expression (100%), which in combination with heparin (10 U/ml), led to a pulling
      apart of the fibroblastic sheet, simulating contraction. Under serum-free
      conditions, with or without bFGF and heparin, primary corneal fibroblasts
      appeared morphologically similar to in situ corneal keratocytes, demonstrating a
      broad, stellate morphology with interconnected processes and no alpha-SM actin
      expression. Addition of TGF beta 1 to serum-free cultures resulted in a dramatic
      transformation of corneal keratocytes to spindle-shaped, fibroblast-like cells
      that expressed alpha-SM actin in 100% of cells and exhibited a 20-fold increase
      in fibronectin synthesis and a 13-fold increase in alpha 5 beta 1-integrin
      synthesis. These effects were blocked by the addition of neutralizing antibodies
      (16 micrograms/ml). Overall these data suggest that TGF beta 1 is a potent
      modulator of myofibroblast transformation under serum-free conditions. In
      addition, the growth of keratocytes in serum appears to mimic, in part, in vivo
      activation and myofibroblast transformation. We conclude that detailed study of
      TGF beta 1-induced myofibroblast transformation under defined serum-free
      conditions will provide important insights into the myofibroblast transformation
      process.

PMID- 8862929
TI  - Effect of amniotic fluid in corneal sensitivity and nerve regeneration after
      excimer laser ablation.
AB  - To examine the effect of topical application amniotic fluids on the recovery of
      corneal sensitivity and nerve regeneration after excimer laser photokeratectomy,
      excimer laser was applied to 18 rabbits (VISX 20/20, 5 Hz, 7 microns depth: nine
      rabbits; 100 microns depth: nine rabbits). Human amniotic fluid (AF) was
      topically applied to the right eyes (AF group), and a balanced salt solution
      (BSS) was applied to the left eyes (BSS group). Corneal sensitivity was measured
      by using a Cochet-Bonnet aesthesiometer after weeks 1, 2, 4, 5, 8, and 12. Nerve
      regeneration status was evaluated after weeks 2, 4, 5, 8, and 12 by gold chloride
      staining. Corneal sensitivity was initially subnormal and recovered close to the
      normal level at week 8. The sensitivity was higher in the AF group than in the
      BSS control group, except at week 2. Subepithelial nerve regeneration at the
      laser site was detected both at week 4 in the AF group and at week 5 in the BSS
      group. There was no significant correlation between the nerve-regeneration state
      and sensitivity changes. Long striated nerve regeneration from the deep stromal
      nerve was remarkable at the third month, especially in the BSS group. The BSS
      group showed more marked scarring of the superficial stroma, compared with the AF
      group. The nerve regeneration at the scar site was discontinued and delayed.
      Subepithelial leash nerves in the AF group were more abundant than those in the
      BSS group. The recovery of sensitivity and nerve regeneration were faster in the
      AF cornea than in the BSS cornea. These results suggest that the factors in AF
      helped the recovery of corneal sensitivity, nerve regeneration, and reduced scar
      formation.

PMID- 8862930
TI  - Effects of basic FGF and TGF beta 1 on F-actin and ZO-1 organization during cat
      endothelial wound healing.
AB  - Previous studies suggest the existence of two separate and distinct mechanisms of
      endothelial wound healing (i.e., cell migration and cell spreading), which may be
      controlled by unique, injury-dependent, wound-related factors. The purpose of our
      study was to evaluate potential biologic mediators regulating healing of the
      growth arrested cat endothelium by using an ex vivo, organ-culture model. Three
      buttons were punched from each cornea of 11 cats with a 6-mm trephine. A 1- to 2
      mm diameter endothelial scrape injury (SI) was made, and buttons were cultured in
      (a) serum-free media (SFM), (b) serum plus media (20% fetal calf serum), (c) SFM
      plus basic fibroblast growth factor (bFGF), (d) SFM plus bFGF and heparin, (e)
      SFM plus transforming growth factor-beta 1 (TGF beta 1), or (f) SFM plus TGF beta
      1 and anti-TGF beta 1. At various times from 8-48 h after injury, buttons were
      stained with phalloidin and anti-ZO-1, and imaged by using laser scanning
      confocal microscopy. Evaluation of SI in cat corneal buttons under serum-free
      conditions showed maintenance of normal endothelial differentiation, indicating
      that the organ-culture SI model mimics in vivo SI. Addition of TGF beta 1
      produced a dramatic reorganization of apical F-actin and development of stress
      fibers, as well as the loss of normal cell border-associated ZO-1 distribution.
      The effects of TGF beta 1 were blocked by the neutralizing antibodies to TGF beta
      1. Addition of serum or bFGF produced much less pronounced changes in F-actin and
      ZO-1 distribution. These results suggest that TGF beta 1 may play a critical role
      in modulating the wound-healing response of the corneal endothelium.

PMID- 8862931
TI  - Povidone-iodine (betadine) in the treatment of experimental Pseudomonas
      aeruginosa keratitis.
AB  - Topical 5% povidone-iodine for the treatment of corneal ulcers was observed in
      Sierra Leone, West Africa by one of us (D.J.D.). To test the efficacy of topical
      5% povidone-iodine for infectious keratitis, experimental Pseudomonas aeruginosa
      keratitis was induced in 12 rabbits by first abrading the central 3 mm of corneal
      epithelium. Thirty milliliters of broth of P. aeruginosa strain ATCC 27835 (1.8 x
      10(7) viable bacteria) was dropped twice on the wounded cornea. After 22 h, all
      corneas were clinically infected. Eight rabbits were treated with 5% povidone
      iodine solution and four with 0.9% NaCl solution. All were given hourly drops.
      Twenty-four hours after treatment began, the central 8-mm button of the infected
      cornea was excised, homogenized, and serial dilutions plated onto MacConkey agar.
      The total number of viable Pseudomonas organisms was calculated. The treatment
      group had 5.2 +/- 0.4 CFUs (colony-forming units) per cornea. The control group
      had 4.8 +/- 0.4 CFUs per cornea (p = 0.11). The clinical scores (Hobden grading
      system) were 6.9 +/- 1.5 for the treated group and 7.3 +/- 2.5 for the control
      group (p = 0.74). There was no statistical difference between the treated and
      control groups. Povidone-iodine (5%) is not effective in the acute treatment of
      P. aeruginosa keratitis in this rabbit model.

PMID- 8862932
TI  - Corneoscleral melt after pterygium surgery using a single intraoperative
      application of mitomycin-C.
AB  - A 59-year-old man underwent pterygium excision with intraoperative application of
      0.2 mg/ml (0.02%) mitomycin-C placed on the scleral bed for 3 min. A sliding
      conjunctival flap was used to cover the exposed limbus and sclera. Five weeks
      after the original surgery, the patient had mild trauma and noted decreased
      vision. At that time, it was noted that he had a corneoscleral melt with
      perforation. The patient was managed with a lamellar transplant in this area.
      Intraoperative single-dose application of topical mitomycin-C can be associated
      with serious complications. This case occurred despite the fact that this patient
      received the lowest dose used in a series of 25 eyes using the same technique
      without any other complications. Although topical mitomycin-C is effective as an
      adjunct to pterygium surgery and may reduce recurrence, the safety and efficacy
      of various concentrations and dosing schedules need further definition.

PMID- 8862933
TI  - Recurrent erosion after photorefractive keratectomy.
AB  - Recurrent erosion of the corneal epithelium has been treated successfully by
      phototherapeutic keratectomy when convention therapy has failed. We present a
      case of recurrent corneal erosion occurring 1 year after photorefractive
      keratectomy in a 55-year-old myopic woman. No corneal abnormalities were
      previously identified in either the affected or the fellow eye. This case
      demonstrates the potential for ineffective healing of the corneal epithelial
      basement membrane complex after excimer laser photorefractive keratectomy.

PMID- 8862934
TI  - Infectious crystalline keratopathy caused by Candida parapsilosis.
AB  - Infectious crystalline keratopathy is a chronic infection of the cornea,
      characterized by branching intrastromal opacities without inflammation. These
      changes are usually due to accumulations of bacterial colonies, most commonly
      viridans streptococci, but this entity has previously been reported in
      association with Candida albicans and Candida tropicalis. We present the case of
      a 66-year-old man who had previously undergone penetrating keratoplasty and
      developed infectious crystalline keratopathy due to Candida parapsilosis.
      Histopathology showed interlamellar accumulations of viable yeasts with no
      inflammation. Chronic topical corticosteroid use in this patient produced
      relative immunosuppression, allowing for the infection by Candida parapsilosis
      and the lack of inflammation in the cornea. The spectrum of causative organisms
      in infectious crystalline keratopathy continues to grow, emphasizing the need for
      laboratory evaluation in the management of this disorder.

PMID- 8862935
TI  - Treatment of adenoviral conjunctivitis with topical cidofovir.

PMID- 8862936
TI  - The efficacy and tolerability of an 8-day administration of intravenous and oral
      meloxicam: a comparison with intramuscular and oral diclofenac in patients with
      acute lumbago. German Meloxicam Ampoule Study Group.
AB  - In this controlled, randomized, parallel and open multicentre study, the efficacy
      and tolerability of a regimen comprising intravenous (i.v.) meloxicam followed by
      oral therapy was compared with a standard regimen of intramuscular (i.m.)
      diclofenac followed by oral dosing in patients with acute lumbago. Of a total of
      183 patients, 92 were randomized to receive meloxicam 15 mg i.v. on day 1
      followed by 7 days oral treatment with one 15 mg tablet daily, and 91 patients
      received diclofenac 75 mg i.m. on day 1 followed by 7 days treatment with one 100
      mg slow release tablet daily. Pain on movement and limitation of activities were
      assessed by patients and physicians using questionnaires. Meloxicam i.v.
      demonstrated a significantly faster median time of onset of analgesic action (30
      minutes), compared with diclofenac i.m. (60 minutes). The reduction in pain
      during movement 30 minutes after injection was also significantly in favour of
      meloxicam. Assessments of global efficacy indicated that meloxicam was
      significantly better than diclofenac as rated by investigators (p = 0.02) and
      patients (p = 0.01). Moreover, the rating of investigators and patients for local
      and global tolerance was significantly in favour of meloxicam (p < 0.05) and
      improvements in the quality of life were almost significant (p = 0.053). Fewer
      adverse events, particularly of a gastrointestinal (GI) nature, occurred in the
      meloxicam group compared with the diclofenac group. This study therefore
      demonstrates that meloxicam 15 mg i.v. followed by oral therapy is both
      efficacious and well tolerated in the treatment of acute lumbago, and compares
      favourably with the standard NSAID, diclofenac, in this indication.

PMID- 8862937
TI  - LDL subfractions and atherogenicity: an hypothesis from the University of
      Glasgow.
AB  - The variation in the size and atherogenicity of the low density lipoprotein (LDL)
      particles has attracted a great deal of recent attention. In particular,
      attention has focused on the role of plasma triglyceride concentrations in
      driving the lipoprotein exchange that determines the concentration of the
      smaller, denser, more atherogenic LDL fraction. In a study at Glasgow University,
      researchers analysed the distribution of LDL subfractions among
      normocholesterolaemic men, with or without coronary artery disease, survivors of
      myocardial infarction, and normal controls. The results showed that the risk of
      coronary artery disease or myocardial infarction is considerably greater in those
      groups with higher plasma concentrations of small, dense LDL. In a second study,
      eight patients with hypercholesterolaemia were treated with fenofibrate.
      Radioisotope tracers showed that fenofibrate shifts the distribution of LDL
      subfractions from small, dense, atherogenic particles towards larger, lighter,
      less atherogenic ones. The efficacy of fenofibrate derives from its
      hypotriglyceridaemic activity. Triglycerides may have further atherogenic and
      thrombogenic effects: they may cause endothelial cell dysfunction in the artery
      wall, stimulating the recruitment of macrophages into the endothelium. They may
      also promote the synthesis of thrombogenic mediators, suppressing local plasmin
      synthesis and accelerating intra-arterial fibrin deposition. This evidence has
      led to an increasing recognition of the central role of triglycerides in the
      process of atherogenesis.

PMID- 8862938
TI  - Topical therapy of allergic rhinitis in childhood: Allergodil nasal spray--non
      sedating in children.
AB  - The efficacy and safety of the nasally administered drug Allergodil in the
      treatment of allergic rhinitis were evaluated in a prospective drug monitoring
      programme conducted in Germany. Data from 489 children under the age 13 were
      included. The study was designed to gain knowledge about Allergodil in a normal
      clinical setting. Dosing was at the judgement of the investigator bearing in mind
      data sheet recommendations, i.e. one spray-puff (0.14 mg) per nostril twice
      daily. Patients were treated for four weeks. The occurrence of ten nasal, eye and
      throat symptoms was rated (0 = never, 1 = sometimes, 2 = often). All symptoms
      showed a statistically significant improvement at the final visit, as did the
      overall sums of the scores. These changes were clinically significant. Overall
      assessment of efficacy by the physicians and the patients was very good and good
      in more than 85% of patients. 70% of patients required no concomitant medication.
      13.5% of patients experienced adverse events, mostly mild or moderate in
      severity. Safety and tolerance were assessed as very good and good in more than
      97% of cases. No sedation was seen. With respect to both efficacy and safety,
      there were no differences between patients younger than 6 years and those aged 6
      12 years. In conclusion, these results suggest that Allergodil is an effective
      treatment of the symptoms of allergic rhinitis in children. The subgroup of 48
      young patients studied shows that Allergodil was safe and well tolerated in
      patients aged 2-6 years.

PMID- 8862939
TI  - The value of nifedipine in the treatment of hypertension, coronary heart disease
      and myocardial infarction (post-infarction therapy).
AB  - Calcium antagonists are among the drugs most often prescribed in the treatment of
      cardiovascular diseases. Among the 2000 preparations most often prescribed in
      Germany in 1994, there were 48 calcium antagonists which presented a prescription
      rate of 1268 million defined daily doses. Calcium antagonists of the nifedipine
      type are by far the most often prescribed preparations of this group. They are
      targeted mainly against hypertension and coronary heart disease, with post
      infarction angina pectoris also featuring among their indications. Recent
      publications have, in consideration of indications on possible risks associated
      with nifedipine medication, fanned discussions on the pros and cons of nifedipine
      medication and thus the value of calcium antagonists in treating hypertension and
      CHD as well as post-infarction patients. The purpose of this report is to analyze
      the current situation and to draw conclusions for the practical use of calcium
      antagonists.

PMID- 8862940
TI  - Double-blind parallel study of a combination of chlorthalidone 50 mg and
      triamterene 50 mg in patients with mild and moderate hypertension.
AB  - In a double-blind, partial cross-over study of 141 patients with mild to moderate
      hypertension, chlorthalidone 50 mg was compared with chlorthalidone 50
      mg/triamterene 50 mg combination treatment. The study assessed clinical efficacy
      in the reduction of blood pressure, and safety with regard to serum potassium
      concentration and adverse reactions. Both treatment regimens were found to offer
      equivalent therapeutic success, but the decrease in serum potassium concentration
      was significantly less with the combination treatment than with chlorthalidone
      alone.

PMID- 8862941
TI  - The effect of 5-aminosalicylate and para-aminosalicylate on the synthesis of
      prostaglandin E2 and leukotriene B4 in isolated colonic mucosal cells.
AB  - The effect of 5-aminosalicylate (5-ASA) and para-aminosalicylate (PAS) on the
      synthesis of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) was studied in 24
      healthy volunteers. Both drugs are successfully used in the treatment of chronic
      inflammatory bowel disease, but the biochemical pathway of their anti
      inflammatory action is still unknown. Biopsies were taken from the descending
      colon and were isolated biochemically. 5-ASA, PAS and a control were added to the
      suspension of isolated colonic mucosal cells and incubated over 0-45 min. Both 5
      ASA and PAS did not alter the PGE2 production but, compared with PAS and the
      control, 5-ASA decreased the LTB4 synthesis in a dose-related fashion. As a
      result, the LTB4/PGE2 ratio was significantly diminished by 10(-4) mol/l 5-ASA.
      These findings are consistent with those of other authors, indicating that 5-ASA,
      at least in part, modulates the colonic eicosanoid synthesis. In contrast, PAS
      did not influence the mucosal production of PGE2 and LTB4 and therefore must
      exert some other biochemical action in order to explain its therapeutic effects
      in the treatment of Crohn's disease or ulcerative colitis.

PMID- 8862942
TI  - The thrifty genotype hypothesis: how does it look after 30 years?

PMID- 8862943
TI  - The aetiology and management of erectile, ejaculatory, and fertility problems in
      men with diabetes mellitus.
AB  - Erectile impotence is more common in the diabetic than the general population,
      occurs at a younger age, and is often associated with ejaculatory problems. For
      these, and possibly for other more subtle reasons, fertility may be a problem for
      men with diabetes. The symptoms of erectile and ejaculatory dysfunction are
      frequently not discussed between patient and doctor. Psychological factors are
      important but the vast majority of diabetic patients have an organic basis for
      their impotence. Both neurogenic and vascular factors are important in the
      pathogenesis of erectile failure. Autonomic neuropathy is almost certainly the
      cause of the ejaculatory failure that may be present in up to 40% of men with
      diabetes. The final biochemical mediator of erection within the penile erectile
      tissue is nitric oxide and a key enzyme in its degradation is phosphodiesterase
      (type V). Drugs that affect the metabolism of this enzyme are being developed to
      treat erectile failure. At present, the self injection of intra-cavernosal
      erectogenic agents (such as prostaglandin E1) provide the main form of therapy
      for erectile failure. Vacuum devices are a simple alternative and venous ligation
      surgery may be effective for a properly selected cohort of patients. Prosthetic
      implants are a final option for patients in whom all else has failed. Fertility
      problems, particularly when associated with ejaculatory failure can be overcome
      with modern assisted reproductive techniques. Nowadays, these will frequently
      involve gamete micro-manipulation.

PMID- 8862944
TI  - Acute effect of insulin on autonomic regulation of the cardiovascular system: a
      study by heart rate spectral analysis.
AB  - Insulin is suggested to have direct effects on the cardiovascular system but
      these are not well described. We assessed the possible influence of insulin on
      autonomic control of heart function. A 2-h hyperinsulinaemic euglycaemic clamp
      was performed in 10 healthy women (mean age 21.7 +/- 1.3 years), at two different
      insulin infusion rates: 80 mU m-2 and 400 mU m-2 min-1, in 7 and 3 subjects,
      respectively. Saline alone was infused in 4 controls. Power spectral analysis
      (PSA) of heart rate was recorded before and after 90-120 min of insulin infusion,
      as were blood pressure and heart rate. Although there were no significant changes
      in heart rate or blood pressure, PSA showed marked reductions of high frequency
      (HF) bands after insulin (2.60 +/- 0.12 vs 2.09 +/- 0.16 log ms2, p < 0.005), as
      at both low and high infusion rates (2.46 +/- 0.13 to 2.14 +/- 0.23 log ms2, p <
      0.05, and 2.92 +/- 0.18 to 1.98 +/- 0.06 log ms2, p < 0.01, respectively). There
      were no significant changes of low frequency (LF) bands. Densities at LF and HF
      did not change significantly in control studies. As HF and LF are considered to
      reflect parasympathetic and mainly sympathetic control respectively, our
      observation of an increased LF/HF ratio (0.13 +/- 0.10 vs 0.63 +/- 0.13, p <
      0.005) may be considered an index of relative sympathetic predominance induced by
      insulin infusion. We conclude that insulin affects the cardiovascular system,
      reducing vagal influence on the heart and inducing a relative hypersympathetic
      tone.

PMID- 8862945
TI  - Abnormal antioxidant status in impaired glucose tolerance and non-insulin
      dependent diabetes mellitus.
AB  - A total of 105 subjects with impaired glucose tolerance were classified into two
      groups, 51 subjects with plasma glucose > 11.1 mmol l-1 in one of the blood
      samplings during OGTT, but at 2 h being less than < 11.1 mmol l-1 were classified
      as early hyperglycaemics. Fifty-four cases were classified as true IGT, with
      fasting plasma glucose < 7.8 mmol l-1 and post plasma glucose level between 7.8
      and 11.1 mmol l-1. Age and sex matched groups of normals (healthy adults) and
      NIDDM cases without symptomatic secondary complications were also included in the
      study. Lipid peroxidation (LPO) product in plasma, erythrocyte, and erythrocyte
      cell membrane were found to be significantly elevated (p < 0.001) in IGT, early
      hyperglycaemia and diabetes mellitus while glycosylated haemoglobin was also
      higher. Antioxidant enzymes superoxide dismutase and catalase were significantly
      lower in red blood cells obtained from IGT and early hyperglycaemic groups. They
      were closer to the levels showed in NIDDM confirming that antioxidant deficiency
      is already present in subjects classified as impaired glucose tolerant. Among the
      antioxidant scavengers, reduced glutathione (GSH) and ascorbic acid are reduced
      by 15% and 20% in IGT and NIDDM, respectively. We conclude that antioxidant
      status is poor in both IGT and NIDDM, suggesting an overlap of frank diabetic
      state in those classified as IGT. It is possible that antioxidant therapy might
      retard progression from IGT to NIDDM.

PMID- 8862946
TI  - Levels of von Willebrand factor, insulin resistance syndrome, and a common vWF
      gene polymorphism in non-insulin-dependent (type 2) diabetes mellitus.
AB  - To examine the association between von Willebrand Factor (vWF) concentrations and
      features of the insulin resistance syndrome, 208 patients with Type 2 (non
      insulin-dependent) diabetes (NIDDM) and 80 healthy controls were studied. A
      restriction fragment length polymorphism in exon 12 of the vWF gene, detected by
      Aat II endonuclease, was also examined. vWF concentrations were elevated in the
      patient group (patients 1.28 IU ml-1 vs controls 1.12 IU ml-1, p = 0.003).
      Genotype frequencies were in Hardy-Weinberg equilibrium and genotype did not
      relate to vWF levels: means (95% CI) were AA 1.29 (1.29-1.44) IU ml-1 n = 3; AG
      1.28 (1.22-1.26) IU ml-1 n = 48; GG 1.29 (1.25-1.39) IU ml-1 n = 155. vWF
      correlated with age (r = 0.23 p < 0.0005), duration of diabetes (r = 0.23, p <
      0.001), and fibrinogen (r = 0.22, p = 0.002) in the patient group, but was
      unrelated to blood lipids, HbA1C, body mass index, glucose, hypertension, and
      smoking. In a linear regression model, age and insulin remained as independent
      predictors of vWF levels, explaining 16% of inter-individual variance in the
      patient group. In conclusion, these findings show vWF concentrations are elevated
      in NIDDM and are weakly related to features of the insulin resistance syndrome.
      No relationship was demonstrated between the gene polymorphism studied and vWF
      concentrations in this group.

PMID- 8862947
TI  - The management and outcome of critical limb ischaemia in diabetic patients:
      results of a national survey. Audit Committee of the Vascular Surgical Society of
      Great Britain and Ireland.
AB  - It is generally considered that the outcome from critical limb ischaemia (CLI) in
      people with diabetes is inferior to that in non-diabetic patients. However,
      excellent results have been reported in diabetic people with the use of bypass
      surgery to pedal arteries. Data from a prospective national survey on CLI have
      been analysed to compare surgical practice and outcome from CLI in diabetic and
      non-diabetic populations. Of 679 limbs included in the survey, 204 (30%) were in
      diabetic patients. Thirty-seven (18%) of diabetic limbs were treated by primary
      amputation compared to 43 (9%) in non-diabetics (p = 0.0013). Revascularization
      was the primary treatment intention in 127 (62.3%) of diabetic limbs compared to
      342 (72%) in non-diabetics (p = 0.01). Bypass to pedal arteries was reported in
      only 2 (1%) diabetic patients. The limb salvage rate in diabetic patients was
      60%, compared to 72.5% for non-diabetic patients (p = 0.0013). The mortality
      rates were 15% and 12% in diabetic and non-diabetic patients, respectively (NS).
      These results confirm that in the UK and Ireland diabetic patients with CLI fare
      considerably worse than do people without diabetes. The results may be improved
      if more pedal artery reconstructions were performed.

PMID- 8862948
TI  - Social consequences of insulin-dependent diabetes mellitus are limited: a
      population-based comparison of young adult patients vs healthy controls.
AB  - In a population-based study, the social situation of 91 young adult patients with
      Type 1 diabetes mellitus (IDDM) since childhood was compared to that of an age-
      and sex-matched group of 189 healthy persons. Their mean age was 37.2 years,
      duration of diabetes 28.7 years and severe complications were present in 13 of
      the 91 patients. A nearly 10-fold increased mortality rate was found in diabetic
      patients, mainly due to diabetic nephropathy and trauma, including suicide. The
      employment rate was lower in diabetic patients (71% vs 85%, p < 0.05); the need
      for welfare benefits was greater (15% vs 3%, p < 0.01). These differences were
      mainly the consequence of diabetic late complications. Education, housing
      conditions, life style, civil state, alcohol and smoking habits were similar in
      both groups. Confidence in the future was slightly less in diabetic patients (p <
      0.05). In conclusion, besides an increased mortality rate, the present study has
      shown no serious social consequences in adult Type 1 diabetic patients without
      severe late complications, as compared to matched controls. Our results indicate
      that IDDM affects social life only to a limited extent, in the absence of severe
      vascular complications.

PMID- 8862949
TI  - Geographical mapping of childhood diabetes in the northern English county of
      Yorkshire.
AB  - This study aimed to highlight geographical differences in childhood Type 1
      (insulin dependent) diabetes mellitus (IDDM) by mapping incidence at 3 different
      geographical scales, within the northern English county of Yorkshire. Mapping
      techniques are applied to incident cases from a population-based regional
      register of childhood IDDM. The Yorkshire Children's Diabetes Register (YCDR)
      comprises 1310 children (0-14 years) diagnosed with IDDM from 1978-1990. Age
      standardized incidence rates (cases/100000/year) are given for administrative
      county, standardized incidence ratios (SIRs) are mapped by local government
      district and electoral ward. Heterogeneity between areas was assessed by a chi 2
      test. At county level, incidence is 25% higher in Humberside (16.82 per 100000
      per year) compared to West Yorkshire (12.21 per 100000 per year) (p < 0.001).
      SIRs for the 22 districts display significant heterogeneity (p < 0.001) with
      deficits in the urban areas of Kirklees (70 95% CI 57-85) and Bradford (81 95% CI
      68-95) and significant excesses in the rural districts of Ryedale (147 95% CI 106
      198), Beverley (149 95% CI 113-193), Holderness (166 95% CI 112-237) and
      Boothferry (186 95% CI 134-250). At the smallest scale, variation between wards
      is significant (p < 0.001) and low incidence in urban areas is notable.
      Geographical variation in the incidence of childhood IDDM may provide strong
      clues to its aetiology. Within Yorkshire, geographical distribution shows
      significant heterogeneity at three different scales. The magnitude of the
      variation is not explained by ethnic or genetic differences in the population and
      underlines the important influence of environmental factors in disease aetiology.

PMID- 8862950
TI  - The incidence of diabetes mellitus in an English community: a 20-year follow-up
      of the Whickham Survey.
AB  - The original Whickham Survey documented the prevalence of diabetes and lipid
      disorders in a sample of 2779 adults aged 18 years and over, which matched the
      British population structure. The aim of the 20-year follow-up study was to
      determine the incidence and natural history of diabetes. Outcomes in terms of
      morbidity and mortality at follow-up were determined in over 97% of the original
      population. Ninety-four subjects had been identified and treated for diabetes
      since the first survey, including 17 subjects identified as having a fasting
      plasma glucose > or = 7.8 mmol l-1 at follow-up. The incidence of diabetes for
      the total population was 2.2 1000-1 year-1 (95% confidence interval 1.8, 2.6).
      The risk factors identified at first survey were corrected for age, cut-off at
      the 95 centile and entered into a log linear model. Those which strongly
      predicted development of diabetes in the total population were fasting blood
      glucose (odds ratio (OR) (with 95% confidence intervals) = 2.3 (1.5, 3.5)) and
      body mass index (OR = 2.2 (1.5, 3.3)) in men, and fasting blood glucose (OR = 2.6
      (1.7, 4.1)) and fasting serum triglyceride (OR = 2.8 (1.8, 4.4)) in women. A
      logit model has enabled the calculation of the probability of developing diabetes
      20 years later. It was the characteristics of becoming older such as obesity,
      hypertriglyceridaemia, and raised fasting blood glucose, rather than age itself,
      which were associated with the development of diabetes.

PMID- 8862951
TI  - Why does ethnicity affect prevalence of gestational diabetes? The underwater
      volcano theory.
AB  - To study why gestational diabetes (GDM) is more common in some ethnic groups than
      others, we tested the hypothesis that GDM is more common in people who are
      temporally closer to developing non-insulin-dependent (Type 2) diabetes mellitus
      (NIDDM). The prevalence of GDM and the mean age of affected women in each major
      ethnic group were determined. From our database of NIDDM 6052 patients, the mean
      age of onset in each ethnic gorup was calculated and the mean difference between
      age of developing GDM and age of developing NIDDM derived (NIDDM-GDM age gap).
      This age gap was used to adjust for the susceptibility to GDM of each group. The
      overall prevalence of GDM was 6.7% (CI 6.0%-7.4%). In Anglo-Celtic women it was
      3.0% (CI 2.3%-3.7%). For the other ethnic groups the prevalence and odds ratio
      (OR) were: Chinese (15.0% CI 11.8%-18.2% OR 5.6), Vietnamese (9.6% CI 6.6%-12.5%
      OR 3.6), Indian (16.7% CI 9.8%-23.5% OR 6.4), Arabic (7.3% CI 4.6%-10.1% OR 2.5)
      and Aborigines (10.1% CI 3.8%-16.4% OR 3.7). The OR for susceptibility to GDM did
      not change after adjustment for BMI and maternal age and it correlated
      significantly with the NIDDM-GDM age gap (r = -0.85; p = 0.03). However, it fell
      substantially after adjustment for NIDDM-GDM age gap. For women of different
      ethnic origins there is a difference in the time gap between their pregnancies
      and the time at which they would on average be expected to develop diabetes. This
      difference may be an important factor underlying the higher prevalence of GDM in
      some ethnic populations.

PMID- 8862952
TI  - Effect of metformin on intact proinsulin and des 31,32 proinsulin concentrations
      in subjects with non-insulin-dependent (type 2) diabetes mellitus.
AB  - We have investigated the effects of metformin treatment on concentrations of
      proinsulin-like molecules in subjects with Type 2 (non-insulin-dependent)
      diabetes mellitus. Metformin was given for 12 weeks in an increasing dose up to
      850 mg three times daily in a double-blind placebo-controlled cross-over design
      to 27 subjects (age 53.0 +/- 9.9 years; 19 male, 8 female). Concentrations of
      insulin and proinsulin-like molecules were measured by highly specific
      enzymoimmunometric assays. The end of metformin treatment was compared with end
      of placebo treatment. Metformin lowered fasting plasma glucose concentrations (at
      12 weeks, metformin: 8.0 +/- 2.5 vs placebo: 12.0 +/- 2.3 mmol l-1, p r2 0.001;).
      Concentrations of intact (median change -2.9 (range -28.4 to +2.5 pmol l-1), p =
      0.02) and des 31,32 proinsulin (median change -1.6 (range -14.1 to +5.4 pmol l
      1), p = 0.07) and percentage of proinsulin-like molecules were reduced by
      metformin treatment (median change -6% (range -16% to +6%), p = 0.02). Changes in
      the ratio of proinsulin-like molecules were significantly related with those in
      fasting plasma glucose (r1 = 0.69, p < 0.001). Changes in concentrations of
      intact and des 31,32 proinsulin on metformin were not related to changes in body
      mass index or fasting glucose concentration or changes in concentrations of total
      triglyceride, cholesterol, and plasminogen activator inhibitor-1. Therefore,
      metformin treatment in subjects with Type 2 diabetes mellitus significantly
      reduced concentrations of proinsulin-like molecules over a 12-week period.
      However, these changes were not related to changes in cardiovascular risk factors
      seen during metformin treatment. We conclude that short-term effects of metformin
      treatment on proinsulin-like molecules are similar to those previously observed
      with dietary treatment in subjects with Type 2 diabetes but opposite to those of
      sulphonylurea treatment. The effect of long-term treatment with metformin on
      proinsulin-like molecules needs to be assessed.

PMID- 8862953
TI  - Urinary glycosaminoglycan excretion in NIDDM subjects: its relationship to
      albuminura.
AB  - Nephropathy is a serious microvascular complication of diabetes mellitus which is
      preceded by a period of microalbuminura. Increased loss of proteoglycan (PG) from
      glomerular basement (GBM) has been postulated to alter glomerular charge
      selectivity which contributes to urinary loss of albumin. In this study we
      measured the excretion of urinary glycosaminoglycans (GAG), the degradation
      products of PG, in 82 non-insulin-dependent (NIDDM) (Type 2) diabetic and 34 non
      diabetic subjects. We found that diabetic subjects had a significantly higher GAG
      urinary excretion rate compared to non-diabetic subjects (12.54 +/- 5.67 vs 8.80
      +/- 3.99 micrograms glucuronic acid min-1, p = 0.0001). Categorizing for
      albuminuric status shows that the diabetic normo-, micro- and macroalbuminuric
      groups have a higher GAG excretion rate than non-diabetic subjects. Heparan
      sulphate (HS) GAG urinary excretion was measured in 25 samples from diabetic
      subjects and 18 non-diabetic subjects. Diabetic subjects excreted more HS GAG
      than controls both as a rate or as a percentage of total GAG (3.70 +/- 1.94 vs
      2.38 +/- 1.48 micrograms glucosamine min-1, p = 0.02; 31.6% +/- 12.5 vs 23.1% +/-
      10.4, p = 0.02). Categorizing for albuminuric status shows that micro- and macro
      albuminuric groups have a significantly higher HS GAG excretion rate than non
      diabetic subjects. We conclude that, as in IDDM, excretion of GAG and HS GAG is
      higher in NIDDM and may precede the development of microalbuminuria.

PMID- 8862954
TI  - Microalbuminuria screening in the UK: are we meeting European standards?
AB  - European guidelines recommend annual screening for microalbuminuria in patients
      with Type 1 (insulin-dependent) diabetes mellitus (IDDM) of greater than 5 years'
      duration and in those with Type 2 (non-insulin-dependent) diabetes mellitus
      (NIDDM) from diagnosis. To determine the current provision of screening for
      microalbuminuria we performed a postal survey of all diabetologists in the United
      Kingdom. Of 556 questionnaires sent, 326 (59%) were returned (246 adult, 57
      paediatric, 3 adolescent clinics) and of these 306 (55%) were suitable for
      analysis. Screening programmes have been established by 210 (69%) diabetologists:
      70 of these in the last 2 years. 46 more plan to screen patients with IDDM within
      2 years. 155 (92%) of 169 adult programmes perform annual screening in IDDM, 74%
      according to European guidelines (39% in NIDDM). Other clinics use age, type of
      diabetes or criteria such as blood pressure to target screening. An
      albumin/creatinine ratio (52%) on an early morning urine (56%) or random (29%)
      urine sample is most commonly requested. Financial constraint was the principal
      reason given in 32 (33%) of 96 clinics that do not currently screen. Other
      reasons included implementation of other developments with a higher priority
      (24%) and doubts about the medical value of screening (46%). Assuming respondents
      are representative of current UK practice, we conclude that microalbuminuria
      screening is available to patients in many clinics, but is neither universal nor
      always performed according to European guidelines.

PMID- 8862955
TI  - Medial arterial calcification, calcific aortic stenosis and mitral annular
      calcification in a diabetic patient with severe autonomic neuropathy.
AB  - Medial arterial calcification (Monckeberg's arteriosclerosis) is well described
      in diabetic patients with autonomic neuropathy. There is also a high prevalence
      of diabetes mellitus among subjects with calcific aortic stenosis and mitral
      annular calcification. We describe a diabetic patient with autonomic neuropathy
      and extensive medial arterial calcification who also had calcification of the
      aortic valve and of the mitral valve annulus. We propose that autonomic
      neuropathy may play a role in calcification of these structures at the base of
      the heart.

PMID- 8862956
TI  - On diabetes in the elderly.

PMID- 8862957
TI  - Abnormal QTc intervals and autonomic dysfunction.

PMID- 8862958
TI  - The relation of fetal growth to insulin secretion in young men.

PMID- 8862959
TI  - Hypoglycaemia causes functional changes within the chromaffin cells of the
      adrenal medulla.

PMID- 8862960
TI  - Concepts in risk-benefit assessment. A simple merit analysis of a medicine?
AB  - The term 'benefit-risk ratio' is often used as a general term linked to the use
      of a medicine. To balance risk and benefit is, however, a very complex exercise.
      For most medicines the benefits are limited to a few indications and for an
      individual patient there is usually only a single benefit sought but the
      potential risks are multiple. Perceptions of risks versus benefits are influenced
      to a great extent by the context in which they occur. Thus, perception of risk
      may be different to actual risk. In the end in any given situation, the
      acceptable risk-to-benefit balance is an individual judgement on the part of the
      patient or the prescriber. For newer medicines, where there is likely to be
      limited experience, conservative estimates of the overall merit seem preferable
      so that the prescriber will use the drug critically. Subsequently, re-evaluation
      of the risk-to-benefit balance is necessary as greater knowledge of efficacy and
      adverse effects is acquired. It is possible to provide a general 'principle of
      threes' structure for a merit assessment based upon the concepts of seriousness,
      duration and incidence as related to disease indication, disease amelioration by
      a medicine, and the adverse effects ascribed to the medicine. This allows a rapid
      first comparison of medicines for a given indication. In using this general
      conceptual model in a transparent fashion for a given hypothesis and context, it
      is possible to identify the essential data used and assumptions involved that
      make up a merit statement. The quality and value, particularly of risk data, is
      problematic. Risk perception is an issue that needs to be clearly identified
      alongside a merit analysis. A simple merit assessment should pave the way for
      more focused studies.

PMID- 8862961
TI  - A risk-benefit assessment of tramadol in the management of pain.
AB  - Tramadol is a cyclohexanol derivative with mu-agonist activity. It has been used
      as an analgesic for postoperative or chronic pain since the late 1970s, and
      became one of the most popular analgesics of its class in Germany. International
      interest has been renewed during the past few years, when it was discovered that
      tramadol not only acts on opioid receptors, but also inhibits serotonin (5
      hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake. This review
      aims to provide a risk-benefit assessment of tramadol in the management of acute
      and chronic pain syndromes. Tramadol has been used intraoperatively as part of
      balanced anaesthesia. Such use is under discussion, however, as it was associated
      with a high incidence of intraoperative recall and dreaming, and postoperative
      respiratory depression has been described after intraoperative administration of
      high doses. Postoperatively, intravenous and intramuscular tramadol has been used
      with good efficacy. Analgesic doses were comparable with pethidine (meperidine)
      and 10 times higher than morphine. Nausea and vomiting were the most frequently
      reported adverse effects. In controlled studies, haemodynamic and respiratory
      parameters were only minimally impaired. The risk of severe respiratory
      depression in typical dosages is negligible in comparison with other opioids used
      for postoperative pain management. Tramadol has been used with good results for
      the management of labour pain without respiratory depression of the neonate. It
      was also effective for the treatment of pain from myocardial ischaemia, ureteric
      colic and acute trauma. Good results have been published for cancer pain
      management with tramadol in several studies. The potential for abuse or addiction
      seems to be minimal, and serious complications have not been reported. For
      patients with severe pain, the efficacy of morphine is superior, and most
      patients with adequate analgesia from tramadol had to be changed to a more potent
      opioid after a few weeks due to increased nociceptive input during tumour
      progression. Tramadol can be recommended as a safe and efficient drug for step II
      according to the World Health Organization guidelines for cancer pain management.

PMID- 8862963
TI  - Adverse effects of thyroid hormone preparations and antithyroid drugs.
AB  - Thyroid hormone preparations, especially thyroxine, are widely used either at
      replacement doses to correct hypothyroidism or at suppressive doses to abolish
      thyrotropin (thyroid-stimulating hormone) secretion in patients with
      differentiated thyroid carcinoma after total thyroidectomy or with diffuse/
      nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is
      necessary to administer slightly supraphysiological doses of thyroxine. Possible
      adverse effects of this therapy include cardiovascular changes (shortening of
      systolic time intervals, increased frequency of atrial premature beats and,
      possibly, left ventricular hypertrophy) and bone changes (reduced bone density
      and bone mass), but the risk of these adverse effects can be minimised by
      carefully monitoring serum free thyroxine and free liothyronine
      (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides
      [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely
      used antithyroid drugs. They are given for long periods of time and cause adverse
      effects in 3 to 5% of patients. In most cases, adverse effects are minor and
      transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect
      is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life
      threatening condition can now be effectively treated by granulocyte colony
      stimulating factor administration. Other major adverse effects (aplastic anaemia,
      thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly
      rare.

PMID- 8862964
TI  - Nonsteroidal anti-inflammatory drug-induced hepatic disorders. Incidence and
      prevention.
AB  - The nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used
      medications worldwide for the treatment of a variety of common chronic and acute
      inflammatory conditions. The association between NSAIDs and liver disease is
      poorly documented, the exceptions being sulindac and, to a lesser degree,
      diclofenac. The incidence of liver disease is very low and is relatively
      unimportant compared with the risk of peptic ulcer disease and gastrointestinal
      bleeding. Reports of hepatic injury range from insignificant and transient liver
      enzyme elevation to severe and fulminant hepatitis.

PMID- 8862965
TI  - ACE inhibitor-induced cough and bronchospasm. Incidence, mechanisms and
      management.
AB  - A dry, tickly and often bothersome cough is the most common adverse effect of ACE
      inhibitors. Recent studies indicate that cough may develop in around 10% of the
      patients treated with ACE inhibitors. In half of these patients, the ACE
      inhibitor has to be discontinued. Cough has emerged as a class effect occurring
      with all ACE inhibitors with no clear difference between the single substances.
      While ACE inhibition is safe in the vast majority of patients with obstructive
      airways disease, asthmatic symptoms or exacerbation of asthma as well as a rise
      in bronchial reactivity have been occasionally reported. ACE inhibition increases
      the cough reflex. The mechanisms underlying ACE inhibitor-induced cough are
      probably linked to suppression of kininase II activity, which may be followed by
      an accumulation of kinins, substance P and prostaglandins. Physicians should be
      aware that a dry cough is the most common adverse effect of ACE inhibitors and
      that this symptom may occur not necessarily shortly after institution of therapy
      but months or even a year later. Replacement by another ACE inhibitor should not
      be tried, since the cough will almost always recur on rechallenge with the same
      or another ACE inhibitor. After withdrawal of the ACE inhibitor, which is the
      treatment of choice, cough will resolve usually within a few days.

PMID- 8862962
TI  - A risk-benefit assessment of drugs used in the eradication of Helicobacter pylori
      infection.
AB  - Helicobacter pylori is the cause of chronic active gastritis and predisposes to
      peptic ulcer disease (PUD). Furthermore, H. pylori is linked to the pathogenesis
      of gastric lymphoma and gastric cancer. However, treatment of this infection has
      proven difficult. In the last decade, many antimicrobial compounds have been
      studied extensively as monotherapy as well as in combination with bismuth or acid
      suppressive drugs. The individual drugs and the most important eradication
      regimens are discussed with special regard to their risks. In the past, highly
      complex multidrug regimens, fear of adverse effects and frequent eradication
      failures have hampered the broad acceptance of H. pylori-eradication therapies.
      Recently, new 1-week, low-dose combination regimens of 2 antibacterials with a
      proton pump inhibitor have consistently achieved eradication rates of 90% and
      more with an acceptably low rate of adverse effects. One week's standard triple
      therapy [tripotassium dicitrato bismuthate (or bismuth salicylate plus
      metronidazole plus tetracycline or amoxicillin) has been shown to be highly
      effective and tolerated better in combination with a proton pump inhibitor. This
      regimen is, however, more complex and has more adverse effects. Therefore, it is
      not recommended as first-line therapy. Equipped with these therapies physicians
      can now be strongly encouraged to use H. pylori eradication as the therapy of
      choice for patients with PUD and even extend this treatment to other H. pylori
      associated disease conditions.

PMID- 8862967
TI  - Compression? Yes, but for low or high frequencies, for low or high intensities,
      and with what response times?
AB  - Several rationales for using compression in hearing aids are outlined. These
      rationales comprise discomfort avoidance, loudness normalization, noise
      reduction, short term signal dynamic range reduction, empirically determined
      compression, and long-term signal dynamic range reduction. The compression
      systems needed to implement each of these differ greatly, and these differences
      can be viewed as differences in the frequency range undergoing most compression,
      the intensity range undergoing most compression, and the speed at which the
      compressor(s) operate. A classification system along these lines is introduced
      and examples of currently available hearing aids falling into each category are
      given. The effects of each type of compression on speech intelligibility is
      investigated via a review of published research. The results of this indicate
      that, for speech in quiet at a comfortable level, no compression scheme yet
      tested offers better intelligibility than individually selected linear
      amplification. If input level is then decreased and the aid wearer is prevented
      from adjusting the volume control, many types of compression provide
      intelligibility superior to that available from linear amplification. In
      broadband noise, only one system, containing wideband compression followed by
      fast acting high-frequency compression, has so far been shown to provide
      significant intelligibility advantages.

PMID- 8862966
TI  - Antibacterial-induced hepatotoxicity. Incidence, prevention and management.
AB  - Hepatotoxic reactions to antibacterials are rare, occurring with an estimated
      frequency of between 1 and 10 per 100,000 drug prescriptions for most
      antibacterials. Although many antibacterial-induced hepatotoxic reactions have a
      characteristic clinical and biochemical pattern e.g. cholestatic hepatitis
      (flucloxacillin) or fatty liver (tetracycline), many can also present with a
      variety of clinicopathological patterns e.g. nitrofurantoin is associated with
      the development of acute hepatitis, granulomatous hepatitis and chronic active
      hepatitis. Almost all reactions are idiosyncratic, with no diagnostic laboratory
      tests to aid the diagnosis. Early diagnosis is essential and requires a vigilant
      physician to elicit a detailed drug history. Although the outcome is usually good
      when the offending antibacterial is withdrawn, morbidity may persist for years
      and fatalities have occurred, particularly when there is a delay in recognising
      the hepatotoxic antibacterial. There is no specific treatment for antibacterial
      induced hepatotoxicity other than withdrawing the implicated drug. For severe
      disease, however, liver transplantation should be considered.

PMID- 8862968
TI  - Improving consonant intelligibility for Ineraid patients fit with continuous
      interleaved sampling (CIS) processors by enhancing contrast among channel
      outputs.
AB  - OBJECTIVE: In Experiment 1 the objective was to determine whether patients who
      have been implanted with the Ineraid electrode array perform better on tests of
      consonant identification when signals are processed through a continuous
      interleaved sampling (CIS) processor than when signals are processed through an
      analogue (Ineraid) processor. In Experiment 2 the objective was to determine, for
      patients using the CIS strategy, whether identification accuracy for stop
      consonant place of articulation could be improved by enhancing differences in the
      patterns of the signal processor channel outputs. DESIGN: In Experiment 1, 16
      consonants were presented in VCV format for identification. In Experiment 1 the
      CIS patients evidence difficulty in identifying /p t k/. Therefore, in Experiment
      2 the voiceless stop consonants were presented in two stimulus conditions. In
      one, the stimuli were unfiltered. In the other, the stimuli were individually
      filtered so as to enhance the differences in channel outputs for /p/, /t/, and
      /k/. RESULTS: In Experiment 1 the patients performed better with CIS processors
      than with analogue processors. In Experiment 2 the "enhanced" stimuli were
      identified with better accuracy than were the unfiltered stimuli. CONCLUSIONS: We
      confirm that Ineraid patients achieve higher scores on tests of consonant
      identification when using a CIS processor than when using an analogue processor.
      Errors in identification of stop consonant place of articulation, when using a
      CIS processor, are due to the similarity in the patterns of the processor's
      channel outputs. By showing that consonant intelligibility can be improved by
      filtering, we show that we have not reached the limit of speech understanding
      that can be supported by the population of neural elements remaining in our
      patients' auditory systems.

PMID- 8862969
TI  - Topography of auditory evoked long-latency potentials in children with severe
      language impairment: the P2 and N2 components.
AB  - OBJECTIVE: To establish objective neurophysiological correlates of a central
      auditory processing disorder in impaired language development. The study focused
      on the differences in latency, amplitude, and topography of the auditory evoked
      long-latency components, P2 and N2, and the potential diagnostic value of these
      parameters. DESIGN: Topographic maps of the late auditory evoked potentials
      (AEPs) were obtained in a group of 20 children, aged 9 to 15 yr, with severe
      language impairment (LI) and in a control (C) group of 20 normal children.
      Stimulus was a pure tone at 500 Hz with a duration of 100 msec and a rise and
      fall time of 20 msec. The intensity was 75 dB HL. Six test sequences of 50
      stimuli an interval of 1.0 sec were presented to the left and to the right ear
      separately. The AEPs were recorded and analyzed with the Bio-Logic Brain Atlas
      III program. RESULTS: In the topographic maps, a focus of positive potential
      corresponding to P2 (FP2) and a focus of negative potential corresponding to N2
      (FN2) were seen in the majority of children, with a similar distribution in the
      two groups. The latencies of P2 and N2 were significantly longer in the LI group
      than in the C group, P2 showing the most pronounced difference. The amplitudes of
      FP2 and FN2 were lower in the LI group. The diagnostic value of the P2 and N2
      latency, amplitude, and topography in identifying the LI subjects, was estimated
      by means of a scoring system. With all three parameters together, the sensitivity
      was calculated to be 80% and the specificity 80%. Statistical mapping of the
      latency interval of 135 to 305 msec showed z maps with regions of > or = 3 SD in
      14 subjects in the LI group and eight subjects in the C group. CONCLUSIONS: The
      deviations in the LI group indicate slower processing in central auditory
      pathways rather than differences in location and orientation of generators. The
      deviating topography seen in some LI subjects may reflect the various sites and
      extent of cerebral dysfunction. The results also support the idea of different
      generators for the P2 and N2 components. Topographic evaluation of long-latency
      AEPs may become a diagnostic tool in language disorders. The scoring system is a
      potential model in the establishment of individual diagnostic variables.

PMID- 8862971
TI  - Binaural summation of the acoustic reflex.
AB  - OBJECTIVE: The ways in which summation of energy or of information occurs have
      long been used to explore sensory mechanisms. In the case of the acoustic reflex,
      some binaural summation is known to occur, but both data and specification of
      method have been sketchy. Accurate estimates of mean and standard deviation were
      therefore sought to compare binaural acoustic reflex summation (BARS) with
      binaural loudness summation (BLS) to determine whether these have a common basis.
      DESIGN: A specified method was developed for determining reliable acoustic reflex
      values from admittance/intensity functions. Subjects were 34 university students;
      the ages ranged from 18 through 25 yr. For each, the contralateral component of
      the binaural stimulus was presented at a level above the ipsilateral component
      corresponding to the difference in monaural reflex thresholds ("physiologically
      equivalent"). RESULTS: BARS had a mean of 4.4 dB (SD = 3.5 dB), which was
      significantly different from the BLS (mean = 7.6 dB, SD = 1.2 dB). The
      contralateral-ipsilateral difference had a mean of 11.0 dB (SD = 5.1 dB). The
      BARS estimate was not appreciably larger than that found in studies lacking
      correction for physiologic equivalence. CONCLUSIONS: Although the presence of a
      contralateral component elicits a summation or facilitation effect, the
      particular intensity value contributes little to the magnitude of that effect.

PMID- 8862970
TI  - Impaired brain processing in noise-induced tinnitus patients as measured by
      auditory and visual event-related potentials.
AB  - OBJECTIVES: This study aimed to confirm that the brain processing of auditory
      stimuli in tinnitus patients is impaired (Attias, Urbach, Gold, & Shemesh, 1993).
      In addition, possible brain processing dysfunction in response to visual stimuli
      was assessed. DESIGN: Auditory and visual event-related potentials (ERPs) and
      reaction times were recorded in response to a standard oddball target detection
      paradigm. The subjects consisted of 21 noise-induced chronic tinnitus patients
      and 21 age- and hearing-matched control subjects without tinnitus. RESULTS: The
      tinnitus patients had significantly prolonged latencies for the auditory
      nontarget ERP components N1, N2, and P3 and for the auditory target ERP P3
      component. The auditory P3 component was also significantly reduced in amplitude
      for both target and nontarget stimuli for the tinnitus patients. The visual P3
      target and nontarget components were similarly significantly prolonged in latency
      for the tinnitus patients. Reaction times to both target and nontarget stimuli
      were significantly delayed for the tinnitus patients for both stimulus
      modalities. CONCLUSIONS: These findings point to a cortical information
      processing dysfunction in chronic tinnitus patients associated primarily with
      auditory stimuli. ERPs may provide an objective electrophysiologic tinnitus
      measure.

PMID- 8862973
TI  - Breast cancer and magnetic fields.

PMID- 8862972
TI  - Naloxone blockade of (-)pentazocine-induced changes in auditory function.
AB  - OBJECTIVE: In a previous report, we found that intravenous (i.v.) (-)pentazocine
      improved auditory sensitivity and significantly altered compound action potential
      (CAP) amplitudes. Its sigma (sigma)-receptor-selective optical isomer
      (+)pentazocine administered at the same dose was without effect, suggesting that
      the observed auditory neural effects might be mediated by an opioid receptor. To
      directly test this hypothesis, in the present investigation we attempted to
      antagonize the auditory neural effects of (-)pentazocine using the pure,
      nonspecific drug antagonist naloxone. DESIGN: In 25 normal-hearing, male,
      pigmented chinchillas, amplitude and latency changes in the click-evoked auditory
      nerve CAP (N1) and cochlear microphonic (CM) were tracked at six stimulus
      intensities during a baseline period and after the postbaseline administration of
      the opioid drug agonist (-)pentazocine (16 mg/kg; i.v.). In separate groups of
      chinchillas, (-)pentazocine was given alone or administered in combination with
      the standard opioid receptor antagonist naloxone administered at two doses.
      RESULTS: Robust changes in CAP amplitudes after (-)pentazocine occurred in the
      absence of measurable alterations in CAP response latencies, CM amplitudes, or
      blood chemistries and were significantly antagonized when naloxone (5 mg/kg) was
      added to the i.v. infusion. CONCLUSIONS: The observed blockade clearly indicates
      that the agonist effects of (-)pentazocine are opioid receptor-mediated and
      suggests a connection between opioid receptors and auditory neural function.
      Mechanisms of action and the connection between an opioid modulation of auditory
      function and stress, hyperacusis, and tinnitus are discussed.

PMID- 8862974
TI  - Occupational exposure to 60-hertz magnetic fields and risk of breast cancer in
      women.
AB  - We used data from a large population-based case-control study to test the
      hypothesis that women whose "usual occupation" entailed exposure to higher than
      background 60-Hz magnetic fields had a higher risk of breast cancer than women
      without such exposure. Breast cancer cases were identified from four statewide
      tumor registries, and controls were randomly selected from lists of licensed
      drivers and Medicare beneficiaries. Information on usual occupation and breast
      cancer risk factors was obtained by telephone interview. We calculated adjusted
      odds ratios from logistic regression models for women holding occupations with
      potential for low, medium, or high magnetic field exposure, compared with
      background exposure. There was a modest increase in risk for women with potential
      for high exposure [odds ratio (OR) = 1.43; 95% confidence interval (CI) = 0.99
      2.09], and no increase for women with potential for medium (OR = 1.09; 95% CI =
      0.83-1.42) or low (OR = 1.02; 95% CI = 0.91-1.15) exposure The risk among
      premenopausal women in the highest-exposure category was higher (OR = 1.98; 95%
      CI = 1.04-3.78) than for postmenopausal women (OR = 1.33; 95% CI = 0.82-2.17).

PMID- 8862975
TI  - Drinking water nitrate and the risk of non-Hodgkin's lymphoma.
AB  - The increasing incidence of non-Hodgkin's lymphoma (NHL) in the United States is
      only partially explained by known risk factors. Nitrate is a contaminant of
      drinking water in many rural areas. We evaluated its association with NHL after
      accounting for dietary nitrate intake. For 156 cases and 527 controls who used
      Nebraska community supplies, average nitrate exposure was estimated from 1947
      through 1979. Longterm consumption of community water with average nitrate levels
      in the highest quartile (> or = 4 mg per liter nitrate-nitrogen) was positively
      associated with risk [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.1
      3.6]. Dietary nitrate, which came mainly from vegetables, was not associated with
      NHL risk, after adjusting for vitamin C and carotene intakes. Persons with a
      lower intake of vitamin C were at slightly higher risk of developing NHL than
      persons whose daily intake was > or = 130 mg, for all levels of intake of
      drinking water nitrate; our findings were similar for the combined effect of
      water nitrate and carotene intake. Nitrate levels in private wells were measured
      at the time of the interview for 51 cases and 150 controls but were not
      associated with the risk of NHL after adjusting for pesticide use on the farm.
      These findings indicate that longterm exposure to elevated nitrate levels in
      drinking water may contribute to the risk of NHL.

PMID- 8862976
TI  - Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the
      Western Electric Study.
AB  - Dietary factors are likely candidates for important determinants of prostatic
      cancer risk. Among the most investigated nutritional factors have been
      antioxidants. We evaluated dietary beta-carotene and vitamin C in relation to
      subsequent risk of prostate cancer in a prospective study of 1,899 middle-aged
      men. We combined prostate cancer cases diagnosed in the first 24 years of follow
      up with incident cases identified from the Health Care Financing Administration
      hospitalization and outpatient files during an additional 6-year follow-up
      period. We obtained death certificates for all decedents. During the 30-year
      follow-up, prostate cancer developed in 132 men. There was no indication that
      consumption of beta-carotene or vitamin C was related to increased or decreased
      risk of prostate cancer. Relative risks for highest vs lowest quartiles of beta
      carotene and vitamin C intake were 1.27 [95% confidence interval (CI) = 0.75
      2.14] and 1.03 (95% CI = 0.59-1.60), respectively, after adjustment for age,
      number of cigarettes smoked per day, dietary cholesterol and saturated fat,
      alcohol consumption, total energy intake, and occupation. Associations between
      intake of these nutrients and risk of prostate cancer differed depending on
      whether the cancer was diagnosed during the first 19 years of follow-up or the
      next 11 years of follow-up. Overall survival over the 30 years of follow-up was
      positively associated with intake of beta-carotene and vitamin C.

PMID- 8862977
TI  - Evidence of depression provoked by cardiovascular medication: a prescription
      sequence symmetry analysis.
AB  - Many cardiovascular drugs have been implicated as causes of depression. With the
      exception of beta-blockers, few have been studied in formal epidemiologic
      designs. I present a new approach to such analyses that effectively controls for
      confounders that are stable over time. I analyzed the exposure histories of
      11,244 incident antidepressant users, using the Odense University
      PharmacoEpidemiologic Database. All persons starting both beta-blockers and
      antidepressants during a predefined period were identified. If beta-blockers do
      not cause depression, this particular population should show equal numbers of
      persons starting either drug first. A depression-provoking effect of beta
      blockers would generate an excess of persons starting beta-blockers first, that
      is a nonsymmetrical distribution of prescription orders. Confounders causing the
      two drugs to be co-prescribed would rarely be expected to affect the symmetry.
      The initial screening showed nonsymmetrical prescription orders for a wide range
      of cardiovascular drugs. After adjustment for an increasing incidence of
      antidepressant prescribing, I found a depression-provoking effect only for
      angiotensin-converting enzyme (ACE) inhibitors (rate ratio = 1.29; 95% confidence
      interval = 1.08-1.56) and calcium channel blockers (rate ratio = 1.31; 95%
      confidence interval = 1.14-1.51). This prescription sequence symmetry analysis
      may be useful as a screening tool.

PMID- 8862978
TI  - Head injury as a risk factor for brain tumors in children: results from a
      multicenter case-control study.
AB  - We evaluated the risk of brain tumor occurrence in relation to previous head
      injury in a population-based case-control study of 540 children with a primary
      brain tumor and 801 control children. The risk of a brain tumor among children
      with a previous head injury that resulted in medical attention was slightly
      elevated when compared with children with no reported head injury [odds ratio
      (OR) = 1.4; 95% confidence limits (CL) = 1.0, 1.9]. This effect was stronger when
      we restricted the head-injured group to the few children with loss of
      consciousness (OR = 1.6; 95% CL = 0.6, 3.9) or an overnight admission to a
      hospital (OR = 1.7; 95% CL 0.7, 4.6), relative to those with no head injury. We
      observed no appreciable association between brain tumor occurrence and birth
      injury involving the head or a forceps delivery. Among the few children with
      either a birth injury or forceps delivery and a subsequent head injury, we
      observed approximately twofold elevations in risk. The OR was 2.6 (95% CL = 1.1,
      6.9) for those with a birth injury and subsequent head injury, relative to those
      with neither a birth injury nor head injury. Our results provide only weak
      evidence in support of head injury as an etiologic agent for brain tumor
      occurrence in children, although most of our exposed group had only mild head
      injury.

PMID- 8862979
TI  - Imputation for exposure histories with gaps, under an excess relative risk model.
AB  - In reconstructing exposure histories needed to calculate cumulative exposures,
      gaps often occur. Our investigation was motivated by case-control studies of
      residential radon exposure and lung cancer, where half or more of the targeted
      homes may not be measurable. Investigators have adopted various schemes for
      imputing exposures for such gaps. We first undertook simulations to assess the
      performance of five such methods under an excess relative risk model, in the
      presence of random missingness and under assumed independence among the true
      exposure levels for different epochs of exposure (houses). Assuming no other
      source of measurement error, one of the methods performed without bias and with
      coverage of nominally 95% confidence intervals that was close to 95%. This method
      assigns to the missing residences the arithmetic mean across all measured control
      residences. We show that its good properties can be explained by the fact that
      this approach produces approximate "Berkson errors." To take advantage of
      predictive information that might exist about the missing epochs of exposure, one
      might prefer to carry out the imputations within strata. In further simulations,
      we asked whether the method would still perform well if imputations were carried
      out within many strata. It does, and much of the lost statistical power/precision
      can be recovered if the stratification system is moderately predictive of the
      missing exposures. Thus, observed control mean imputation provides a way to
      impute missing exposures without corrupting the study's validity; and stratifying
      the imputations can enhance precision. The technique is applicable in other
      settings where exposure histories contain gaps.

PMID- 8862980
TI  - Absence of confounding does not correspond to collapsibility of the rate ratio or
      rate difference.
AB  - Miettinen and Cook (Am J Epidemiol 1981; 114:593-603) showed that absence of
      confounding does not imply collapsibility of the odds ratio; that is, the crude
      odds ratio need not equal a common stratum-specific odds ratio even if the
      exposed and unexposed study groups have the same distribution of risk factors.
      Less well known is that absence of confounding does not correspond to
      collapsibility of the person-time rate ratio or rate difference. For example, two
      study groups can have the same distribution of all risk factors and yet the crude
      rate ratio need not equal a common stratum-specific rate ratio. The present paper
      provides an example and explanation of this phenomenon. The discrepancy between
      nonconfounding and collapsibility in rate comparisons arises when person-time is
      a post-exposure variable whose distribution can be altered by the effects of
      exposure and other risk factors.

PMID- 8862981
TI  - Effects of disease-dependent changes of exposure in cross-sectional studies.
AB  - The possibility of disease-related changes in exposure is a major limitation of
      many epidemiologic studies. This limitation particularly applies to cross
      sectional studies, in which exposure and presence of disease are measured at the
      same point of time. In some cross-sectional studies, attempts are made to collect
      information not only on current exposure, but also on exposure at some period in
      the past. Various methods have been proposed to assess the relation of past and
      current exposure with disease in such situations. Systematic methodologic work is
      lacking, however, on the performance of these methods in the presence of disease
      related changes of exposure. In this paper, we provide a model to assess the
      effects of such changes, and we illustrate the effects with a variety of
      numerical examples. We show that all of the proposed methods can yield seriously
      biased measures of current exposure effects in the presence of disease-related
      changes in exposure, and we illustrate the direction and order of magnitude of
      the biases. Our results imply that there is usually no alternative to
      longitudinal approaches to measure exposure in relation to disease onset if
      disease-related changes of exposure are of concern.

PMID- 8862982
TI  - Is maternal obesity a risk factor for anencephaly and spina bifida?
AB  - To determine whether the risk of having an infant with anencephaly or spina
      bifida is greater among obese women than among average-weight women, we compared
      307 Atlanta-area women who gave birth to a liveborn or stillborn infant with
      anencephaly or spina bifida (case group) with 2,755 Atlanta-area women who gave
      birth to an infant without birth defects (control group). The infants of control
      women were randomly selected from birth certificates and frequency-matched to the
      case group by race, birth hospital, and birth period from 1968 through 1980.
      After adjusting for maternal age, education, smoking status, alcohol use, chronic
      illness, and vitamin use, we found that, compared with average-weight women,
      obese women (pregravid body mass index greater than 29) had almost twice the risk
      of having an infant with spina bifida or anencephaly (odds ratio = 1.9; 95%
      confidence limits = 1.1, 3.4). A woman's risk increased with her body mass index:
      adjusted odds ratios ranged from 0.6 (95% confidence limits = 0.3, 2.1) for very
      underweight women to 1.9 for obese women.

PMID- 8862983
TI  - Dehydroepiandrosterone sulfate and testosterone are independently associated with
      body fat distribution in premenopausal women.
AB  - To evaluate the relative importance of androgen and insulin concentrations in
      predicting body fat distribution, we measured their association with waist-hip
      ratio in a sample of 151 consecutively enrolled healthy premenopausal women age
      18-24 years, after controlling for potential confounding variables.
      Dehydroepiandrosterone sulfate (DHEAS) and total testosterone were independently
      associated with waist-hip ratio, whereas insulin and free testosterone did not
      appear to play a role of comparable importance. Differences in concentrations of
      circulating DHEAS and total testosterone are independently associated with the
      waist-hip ratio in premenopausal women, providing epidemiologic support to the
      "neuroendocrine dysregulation" hypothesis for the pathogenesis of central
      obesity.

PMID- 8862984
TI  - Underreporting and misclassification of urinary tract cancer cases on death
      certificates.
AB  - We compared the diagnoses for decreased cases with urinary tract cancer reported
      to the Surveillance, Epidemiology, and End Results (SEER) program with their
      underlying cause of death reported on death certificates. Deaths for a
      substantial proportion of cases were ascribed to noncancer causes (bladder, 48%;
      kidney, 28%; renal pelvis, 37%; and other urinary tract, 38%), which decreased
      with advancing stage at diagnosis and increased with length of survival. In
      general, cancer deaths were more likely to be recorded to the predominant subsite
      within an organ. Only 5.5% of renal pelvis cancer patients were recorded to have
      died of their illness, whereas 33.7% of their deaths were reported as due to
      kidney cancer. On the other hand, over 85% of urinary tract cancer deaths
      reported on the death certificates were confirmed by SEER diagnosis, although the
      extent of agreement varied by stage at diagnosis and age at death for kidney and
      renal pelvis cancers.

PMID- 8862985
TI  - Does induced or spontaneous abortion affect the risk of breast cancer?
AB  - The influence of induced or spontaneous abortion on breast cancer risk has been
      the subject of numerous epidemiologic studies over the past decades and has
      recently received heightened attention. Here, we review the evidence to
      understand better the apparent inconsistencies among studies. We considered
      possible biases in data collection, presentation, and analysis that could create
      spurious associations or obscure real relations. A particularly important issue
      is the sensitive nature of abortion, which is a pervasive problem that could
      affect the validity of many studies. Also, an incomplete pregnancy deprives the
      woman of a potentially protective full-term pregnancy and therefore may appear
      harmful when compared with the experience of a woman who did carry to term. The
      dual effect of parity on breast cancer risk-short-term risk increase and long
      term protection-adds another dimension of complexity to the interpretation of
      abortion studies. Long-term influences of abortion may have been insufficiently
      captured in some studies, as follow-up time was too short. Studies to date are
      inadequate to infer with confidence the relation between induced or spontaneous
      abortion and breast cancer risk, but it appears that any such relation is likely
      to be small or nonexistent.

PMID- 8862986
TI  - Amyotrophic lateral sclerosis after long-term exposure to drinking water with
      high selenium content.
AB  - We examined 9 years' incidence of amyotrophic lateral sclerosis, a disease
      previously associated with a high-selenium environment, in a cohort of 5,182
      residents of Reggio Emilia, Italy. This cohort had accidentally been exposed to
      drinking water with high selenium content. Four cases were diagnosed during the
      follow-up. Using the remainder of the municipal population as the reference
      group, the standardized incidence ratio was 4.22 (95% confidence interval = 1.15
      10.80). The standardized incidence ratio was higher after limiting the analysis
      to the subcohort with the longest ascertainable exposure period. The findings
      appear to confirm a causal association between overexposure to environmental
      selenium and amyotrophic lateral sclerosis.

PMID- 8862987
TI  - Use of dipyrone during pregnancy and risk of Wilms' tumor. Brazilian Wilms' Tumor
      Study Group.
AB  - We evaluated the risk of Wilms' tumor in the offspring of women taking various
      medications during pregnancy in a case, control study conducted in Brazil. The
      study accrued 109 cases and 218 age- and gender-matched hospital controls. After
      adjustment for known confounders, we found a strong association with ingestion of
      dipyrone (odds ratio = 10.9; 95% confidence interval = 2.4-50) particularly in
      women from low-income families. Although dipyrone-containing analgesics are
      banned in Europe and North America, they are widely prescribed in Brazil and are
      given as free samples in neighborhood clinics providing free health care. The
      strong effect specific to low-income women may result from higher individual
      consumption compared with women at higher income levels.

PMID- 8862988
TI  - Influence of environmental tobacco smoke on asthma in nonallergic and allergic
      children.
AB  - The relation between exposure to environmental tobacco smoke and childhood asthma
      is not clear. A 1993 study of 892 subjects age 6-17 years (87.5% of 1,019
      eligible subjects) living in Humboldt, Saskatchewan, showed that a lifetime
      history of asthma and asthma attack during the past 12 months were more common
      among allergic children than among non-allergic children. The number of household
      smokers and total daily cigarette consumption by household members were linearly
      related to both lifetime history of asthma and recent asthma in nonallergic
      children, but not in allergic children. Out study indicates that allergic status
      does alter the relation between exposure to environmental tobacco smoke and
      childhood asthma.

PMID- 8862989
TI  - Induced abortion as a risk factor for subsequent fetal loss.
AB  - The relation between past induced abortions and subsequent fetal loss is still
      unclear. We report a case-control study with 331 cases of first spontaneous
      abortion and 993 controls with no previous spontaneous abortion and a normal
      pregnancy at the same period of pregnancy. In comparison with primigravid women,
      the odds ratio for a fetal loss in the current one was 1.41 [95% confidence
      interval (CI) = 0.81-2.43] among women with one previous pregnancy ending in
      induced abortion, 4.43 (95% CI = 1.46-13.36) among those with two previous
      induced abortions out of two pregnancies, and 1.35 (95% CI = 0.64-2.82) among
      women with three or more previous pregnancies ending in one or more induced
      abortions.

PMID- 8862990
TI  - Menstrual patterns and breast cancer mortality in a large U.S. cohort.
AB  - We examined the relation between menstrual irregularity and breast cancer
      mortality in the American Cancer Society Cancer Prevention Study I. In 1959,
      428,653 women age 30 years and older completed a questionnaire on possible cancer
      risk factors, including their recollection of their menstrual pattern at age 20
      years. We used proportional hazards analysis to estimate rate ratios, based on
      2,226 breast cancer deaths over 13 years of follow-up. Women who reported having
      irregular menstruation at age 20 years were at reduced risk for breast cancer
      mortality (rate ratio = 0.84; 95% confidence interval = 0.74-0.96). The relation
      was neither confounded nor modified by other breast cancer risk factors.

PMID- 8862991
TI  - Risk factors for functional ovarian cysts.
AB  - We evaluated risk factors for functional ovarian cysts using data from a case
      control study conducted in Milan. Cases were 68 women with histologically
      confirmed functional cysts. Controls were 272 women admitted to hospital for
      acute conditions. Compared with women who were 11 years of age or younger at
      menarche, women who experienced menarche at 12-13 years or at 14 years or later
      had odds ratios (ORs) of 0.9 [95% confidence interval (CI) = 0.5-1.6] and 0.4
      (95% CI = 0.2-0.9). In comparison with women reporting menstrual cycles lasting
      less than 26 days, the OR was 1.8 (95% CI = 0.7-5.0) in women reporting cycles
      lasting 26-30 days, 1.8 (95% CI = 0.4-7.4) in those reporting cycles greater than
      30 days, and 1.9 (95% CI = 0.4-7.7) in those with totally irregular cycles. Body
      mass was inversely related to the risk of functional ovarian cysts: compared with
      women with a Quetelet index below 20, the OR was 0.9 (95% CI = 0.5-1.7) in those
      with an index in the range from 20-24 and 0.5 (95% CI = 0.2-1.2) in those with an
      index of 25 or more. We found little relation between the risk of functional
      ovarian cysts and education, smoking, marital status, or age at first marriage.
      For oral contraceptive use, we found an OR of 1.3 (95% CI = 0.7-2.6).

PMID- 8862992
TI  - Use of a coded postcard to maintain anonymity in a highly sensitive mail survey:
      cost, response rates, and bias.
AB  - In a survey about euthanasia, 1,600 critical care nurses were randomly assigned
      to receive either three complete, anonymous mailings of the questionnaire or,
      with each mailing, a coded postcard to be returned separately from the
      questionnaire to reduce subsequent mailings to previous responders. The response
      rate in these two groups was 76.5% [95% confidence interval (CI) = 73.6-79.4%]
      and 69% (95% CI = 65.7-72.4%), respectively. The two strategies yielded similar
      responses, and costs were much lower for the postcard group. Using coded
      postcards to be returned separately from completed instruments appears to lower
      the response rate to anonymous mail surveys, but it also lowers cost and may not
      introduce additional bias.

PMID- 8862993
TI  - Should epidemiologists be pragmatists, biostatisticians, or clinical scientists?

PMID- 8862994
TI  - Asbestos-related mortality among Italian migrants to Western Australia.

PMID- 8862995
TI  - Arsenic and bladder cancer mortality.

PMID- 8862996
TI  - Epidemiology differs from public health practice.

PMID- 8862997
TI  - The peril of smokeless tobacco.

PMID- 8862998
TI  - How good is that agreement?

PMID- 8862999
TI  - Seasonality bias in poor reproductive outcome.

PMID- 8863000
TI  - Review: treatment of schizophrenia. State of the art.
AB  - As a result of the multifactorial etiopathology of schizophrenia, a treatment
      strategy combining drug therapy with psychosocial measures is indicated.
      Depending on the stage of the disease and on the individual condition of the
      patient, the accent is set alternatively more on one approach or on the other.
      However, under aspects of symptom reduction and relapse prophylaxis, the therapy
      with neuroleptics plays the most important role. In order to keep their side
      effects to a minimum during acute and long term treatment, there is nowadays a
      trend towards administration of the lowest possible dose. Under this aspect, the
      use of so called atypical neuroleptics should be taken into consideration. The
      treatment of negative symptoms, especially in the context of chronic residual
      syndrome, is still a problem which hasn't been solved to satisfaction. Beside the
      use of atypical neuroleptics, treatment with antidepressives should be tried.
      During the long term relapse prophylactic treatment, it is important that not
      only the criterion "reduction of the relapse rate" but also that of individual
      risk/benefit relation be considered. Concerning psychosocial therapies,
      especially focused behavioural therapy approaches, for example educational
      programs and specific family therapeutical intervention following the high-EE
      concept, as well as training of social and cognitive competences have proved
      useful beside supportive psychotherapy and the whole range of sociotherapeutical
      measures. However they need further evaluation before they get integrated in
      routine treatment.

PMID- 8863001
TI  - Trimipramine: a challenge to current concepts on antidepressives.
AB  - Although it is chemically a classical tricyclic antidepressant agent,
      trimipramine shows atypical pharmacological properties. Its well-documented
      antidepressant action cannot be explained by noradrenaline or serotonin reuptake
      inhibition or by a down-regulation of beta-adrenoceptors. Furthermore, its
      receptor affinity profile resembles more that of clozapine, a neuroleptic drug,
      than that of tricyclic antidepressants. Trimipramine does not reduce, but rather
      increases, rapid eye movement sleep. It stimulates nocturnal prolactin secretion
      and inhibits nocturnal cortisol secretion and may act at the level of the
      hypothalamus on corticotropin-releasing hormone secretion. Trimipramine is of
      particular value in depressed patients with insomnia, and it has been shown to be
      effective in the therapy of primary insomnia. As the pharmacological profile
      indicates, and an open clinical study has shown, trimipramine might also be
      active as an antipsychotic. The drug is both a tool for increasing our
      understanding of depression and a potential therapy for several psychiatric
      disorders.

PMID- 8863002
TI  - Neurological soft signs in schizophrenia: assessment and correlates.
AB  - A German version of the Neurological Evaluation Scale (NES) was administered to
      143 schizophrenic patients, 45 of them being severly chronic and disabled.
      Seventy-eight alcohol-dependent inpatients and 57 healthy volunteers were tested
      as control groups. Neurological soft signs (NSS) were rated with convincing
      agreement. Schizophrenic patients are more impaired on all scales than healthy
      controls. The chronic, severly disabled schizophrenic patients are more impaired
      compared with the main group of schizophrenic patients and both control groups. A
      significant difference between the main group of schizophrenic patients and
      alcohol-dependent patients was only found for the subscale "Motor Coordination".
      Compared with healthy controls the alcohol-dependent patients show a higher NES
      total score. The NES total score was related to the relative width of the third
      ventricle. Total score and subscales were correlated consistently with the level
      of cognitive functioning as measured by the Raven Standard Progressive Matrices
      and various neuropsychological tests presumably sensitive to dysfunctions of the
      prefrontal cortex. The NSS were related to positive as well as to negative
      symptoms, the correlations with negative symptoms being confined to items of
      "Cognitive Disorganization". This close association of psychomotor and cognitive
      dysfunctions may be seen as related to the frequently discussed dysfunctions of
      the prefrontal cortex or the neurointegrative deficit postulated by Meehl.

PMID- 8863003
TI  - Neuropsychological impairment in first-episode and chronic schizophrenic
      patients.
AB  - Patients with first-episode (FE) schizophrenia (n = 40), with chronic
      schizophrenia (n = 40) and healthy controls (n = 40) matched for age, gender,
      education and parental socioeconomic status were administered a battery of
      standardized neuropsychological (NP) tests. Both patient groups showed
      generalized impairment relative to controls and the most pronounced deficits in
      visual-motor processing and attention (VSM). Compared with FE patients, chronic
      schizophrenics performed worse in VSM and abstraction/flexibility. Our findings
      suggest that NP deficits are fundamental manifestations of the illness, and that
      mainly frontally based dysfunctions are more prominent in chronic, kraepelinian
      patients.

PMID- 8863004
TI  - Visual 3D illusion: a systems-theoretical approach to psychosis.
AB  - Binocular depth inversion represents an illusion of visual perception. Such an
      inversion does not occur in all cases, especially when objects with a higher
      degree of familiarity (e.g. photographs of faces) are displayed. Cognitive
      factors are assumed to override the binocular disparity cues of stereopsis. We
      tested the hypothesis that during psychotic and similar states the human CNS is
      unable to correct the implausible perceptual hypothesis. Measurements of
      binocular depth inversion in perception of 3D objects were performed in
      schizophrenic patients (n = 13), in patients with alcohol withdrawal (n = 10), in
      sleep-deprived medical staff (n = 10) and in healthy volunteers (n = 41). The
      binocular depth inversion scores were highly elevated in the patient group and in
      the sleep-deprivated medical staff in comparison with healthy volunteers. The
      data demonstrate that impairment of binocular depth inversion reflects a common
      final pathway, characterized by an impairment of adaptive systems regulating
      perception.

PMID- 8863005
TI  - The Zurich Study: XXII. Epidemiology of gastrointestinal complaints and
      comorbidity with anxiety and depression.
AB  - A representative cohort of Swiss adults recruited at age 20 years and interviewed
      at ages 23, 28 and 30 years was studied regarding the symptomatology, prevalence
      and longitudinal course of functional gastrointestinal symptoms and their
      association with psychiatric syndromes. A functional gastrointestinal complaint
      was identified if a proband reported symptoms at least eight times in the past
      year or for a duration of at least 2 weeks without medical explanation and with a
      moderate degree of distress. Of the population, 9.4-17.7% was found to suffer
      from functional stomach complaints and 4.9-16% from functional intestinal
      complaints. Women reported functional gastrointestinal complaints two to three
      times more often than men, and increasingly so with age. The overlap of stomach
      and intestinal complaints was modest with 2.0-6.7%. Cross sectionally, functional
      stomach complaints were significantly associated with major depression (DSM-III
      R), recurrent brief depression (RBD), subthreshold RBD and dysthymia, and with
      subthreshold panic disorder, agoraphobia, social phobia and recurrent brief
      anxiety. Functional intestinal complaints showed a consistently significant
      association with RBD, dysthymia, major depression, subthreshold RBD, panic
      disorder, subthreshold panic disorder, agoraphobia, simple and social phobia and
      generalized anxiety disorder. Individuals who at younger ages suffered from
      functional gastrointestinal complaints did not show an increased risk for a
      subsequent development of an anxiety or depressive disorder. Functional
      gastrointestinal complaints reflect an unspecific concomitant vegetative
      disturbance common to depression and anxiety; they do not reflect a risk factor
      for the development of a specific anxiety or depressive disorder.

PMID- 8863006
TI  - Suicide in south Tyrol 1980-1992: influence of affiliation to different language
      groups.
AB  - National suicide rates differ widely throughout Europe. The reasons for this are
      still unclear. Besides differences in actual suicide figures, different
      assessment methods and certification strategies have been suggested. This study
      examines the ethnic influence on suicide rates of South Tyrol, an Italian
      province bordering on Austria. The region has historically been under the
      cultural influence of both countries, with its population composed of three
      ethnic groups: the German-, Italian- and Ladinian-language groups. The study
      shows a significant correlation between the male suicide rate and the proportion
      of the German-language group. The ethnic suicide rates of Italian- and German
      speaking people in South Tyrol were found to approximate each other, in
      comparison with the national rates for Italy and Austria, as a possible result of
      cultural interaction.

PMID- 8863007
TI  - Investigations of cytokine production in whole blood cultures of paranoid and
      residual schizophrenic patients.
AB  - In an attempt to define potential immunological dysfunctions in schizophrenia, we
      determined the production of interleukin-2 (IL-2), interleukin-4 (IL-4),
      interferon-gamma (IFN-gamma), and soluble IL-2 receptor (sIL-2R) in a whole-blood
      assay after stimulation with phytohemagglutinin (PHA) as well as the serum
      concentrations of sIL-2R. Because CD4+CD45RO+T cells are the main producers of
      IFN-gamma, we determined the percentage of these cells, as well as of panT,
      CD4+T, and CD8+T cells, by flow cytometry. A whole-blood count was performed in
      addition. Two groups of patients were examined, paranoid-type and residual-type
      schizophrenics. The numbers of both monocytes and neutrophils, but not of
      lymphocytes, were increased significantly in the schizophrenic sample. The IFN
      gamma production of the schizophrenics as a whole group, and of the paranoid
      patients, was reduced significantly in comparison with the control group (p < or
      = 0.05). The residual patients produced less IFN-gamma than the controls, but
      more than the paranoid patients. The latter differences did not reach statistical
      significance. The production of IL-4, which physiologically antagonizes the
      production of IFN-gamma, was not significantly higher in the patient group. No
      changes in the lymphocyte subpopulations were observed. The production of IL-2
      showed a trend toward reduction in paranoid patients, but not in residual
      schizophrenics. The serum sIL-2R levels were elevated slightly in schizophrenics
      when compared with controls. In order to rule out a possible effect of cortisol
      on cytokine production, 20 schizophrenics were compared with 20 age- and gender
      matched controls. However, neither elevated cortisol levels were detected in the
      schizophrenic sample, nor significant intercorrelations between cortisol levels
      and cytokine production, or levels of sIL-2R, respectively. In summary, our data
      reinforce the possibility of immune dysfunction in schizophrenia and point to the
      possible relevance of disease subgroups in this respect.

PMID- 8863008
TI  - Meal frequency; does it determine postprandial lipaemia?
AB  - OBJECTIVE: To determine the effect of altering meal frequency on postprandial
      lipaemia and associated parameters. DESIGN: A randomized open cross over study to
      examine the programming effects of altering meal frequency. A standard test meal
      was given on three occasions following: (i) the normal diet; (ii) a period of two
      weeks on a nibbling and (iii) a period of two weeks on a gorging diet. SETTING:
      Free living subjects associated with the University of Surrey. SUBJECTS: Eleven
      female volunteers (age 22 +/- 0.89 y) were recruited. INTERVENTIONS: The subjects
      were requested to consume the same foods on either a nibbling diet (12 meals per
      day) or a gorging diet (three meals per day) for a period of two weeks. The
      standard test meal containing 80 g fat, 63 g carbohydrate and 20 g protein was
      administered on the day prior to the dietary intervention and on the day
      following each period of intervention. MAJOR OUTCOME MEASURES: Fasting and
      postprandial blood samples were taken for the analysis of plasma triacylglycerol,
      non-esterified fatty acids, glucose, immunoreactive insulin, glucose-dependent
      insulinotropic polypeptide levels (GIP) and glucagon-like peptide (GLP-1),
      fasting total, low density lipoprotein (LDL)- and high density lipoprotein (HDL)
      cholesterol concentrations and postheparin lipoprotein lipase (LPL) activity
      measurements. Plasma paracetamol was measured following administration of a 1.5 g
      paracetamol load with the meal as an index of gastric emptying. RESULTS: The
      compliance to the two dietary regimes was high and there were no significant
      differences between the nutrient intakes on the two intervention diets. There
      were no significant differences in fasting or postprandial plasma concentrations
      of triacylglycerol, non-esterified fatty acids, glucose, immunoreactive insulin,
      GIP and GLP-1 levels, in response to the standard test meal following the
      nibbling or gorging dietary regimes. There were no significant differences in
      fasting total or LDL-cholesterol concentrations, or in the 15 min postheparin
      lipoprotein lipase activity measurements. There was a significant increase in HDL
      cholesterol in the subjects following the gorging diet compared to the nibbling
      diet. DISCUSSION: The results suggest that previous meal frequency for a period
      of two weeks in young healthy women does not alter the fasting or postprandial
      lipid or hormonal response to a standard high fat meal. CONCLUSIONS: The findings
      of this study did not confirm the previous studies which suggested that nibbling
      is beneficial in reducing the concentrations of lipid and hormones. The rigorous
      control of diet content and composition in the present study compared with
      others, suggest reported effects of meal frequency may be due to unintentional
      alteration in nutrient and energy intake in previous studies.

PMID- 8863009
TI  - The effect of reduced extrinsic sucrose intake on plasma triglyceride levels.
AB  - OBJECTIVE: To examine the effect on plasma triglycerides of removing most of the
      extrinsic sugar from the diet of free living hypertriglyceridaemic individuals
      while controlling weight loss. DESIGN: Free living subjects were randomly
      assigned to intervention and control groups. The intervention group undertook to
      consume a "sugar free' diet for six months after a three month baseline period.
      The control group maintained their usual diets for the nine month period. The
      results from the two groups were compared using repeated measures ANOVA.
      SUBJECTS: Thirty two hypertriglyceridaemic individuals, selected from members of
      the public in Dunedin, New Zealand. RESULTS: Subjects in the intervention group
      were able to achieve a mean reduction in sucrose intake of > 70%, largely
      extrinsic sucrose, resulting in a group mean reduction in plasma triglyceride
      levels of > 20% and a mean weight loss over the six month period of about 2%.
      Repeated measures ANOVA on the mean triglyceride figures after the individual
      figures had been adjusted for this small weight loss, showed that there was a
      significant fall in triglyceride levels over the study period compared with the
      baseline. CONCLUSIONS: Hypertriglyceridaemia can be reduced in some individuals
      by the reduction of extrinsic sucrose in the diet. When allowance is made for
      weight loss the reduction is still significant.

PMID- 8863010
TI  - High and low fat consumers, their macronutrient intake and body mass index:
      further analysis of the National Diet and Nutrition Survey of British Adults.
AB  - OBJECTIVES: To explore the different characteristics of high and low fat
      consumers, in particular their macronutrient intake and body mass index. DESIGN:
      Reanalysis of data from the Dietary and Nutritional Survey of British Adults.
      Comparisons were made between groups defined as high and low fat consumers on the
      basis of 7-day weighed food records considered to be valid for energy intake.
      Individuals were classified in two ways according to the percentage energy from
      fat (FAT%) and the absolute amount of fat consumed (FATg). The criteria for
      classification of the high FAT% being > 45% (high fat) and < or = 35% (low fat).
      For the FATg group the threshold for the high fat group was > 138 g/day (men) and
      > 102 g/day (women), and for the low fat group < 85 g/day (men) and < 70 g/day
      (women). SETTING: Dietary data was collected from private households in Great
      Britain between 1986 and 1987. SUBJECTS: From the total population of 2197,
      individuals who were slimming, ill or had an EI: BMR of < 1.2 were excluded in
      order to use data which was most likely to represent habitual energy intakes.
      From the remaining 1240 subjects, 10.8% of this sample (6.1% of the total
      population) were classified as low fat consumers (76 men and 58 women) and 15.4%
      high fat (8.7% of the total population, 93 men and 98 women). MAIN OUTCOME
      MEASURES: Macronutrient consumption and body mass index (BMI). RESULTS: 30% of
      the subjects changed fat group classification when the criteria of defining high
      and low fat groups altered from FAT% to FATg. Nutrient intakes differed according
      to definition of the groups. The high fat FATg group ate significantly more of
      all nutrients than the low fat FATg group. However, this was not seen for the
      FAT% analysis, with the high fat group eating more fat and less carbohydrate. The
      average BMI tended to be higher in the high fat than the low fat groups,
      particularly in the FATg analysis. However, the high fat group contained a wide
      range of BMIs. Further exploration of BMI in the high fat groups, showed that age
      (an 11-year difference) was the only variable to distinguish individuals in the
      top and bottom quartiles of BMI. CONCLUSIONS: High and low fat consumers differ
      according to a number of variables, and this is affected by how these groups are
      defined (FAT% or FATg). High fat consumers tend to have a higher BMI than low fat
      consumers, but not all high fat consumers are overweight or obese.

PMID- 8863011
TI  - Relationship between feeding pattern and body mass index in 220 free-living
      people in four age groups.
AB  - OBJECTIVE: To assess the relationship between feeding pattern and body mass index
      in free-living humans. DESIGN AND SUBJECTS: Feeding pattern was assessed from 220
      7-day weighed dietary records. 187 records were obtained from three separate
      existing studies, and reanalysed. These studies contained data on three age
      groups in the British population; Elderly group (n = 88), Middle-aged group (n =
      40), Working age group (n = 59). A separate study of 13-14 year olds living in
      Croydon was conducted from which 33 usable diet records were collected to produce
      a fourth, Adolescent group. RESULTS: 'Nibbling' and greater energy intakes at
      breakfast were associated with a lower body mass index (BMI) in the Adolescent
      group. In the Middle-aged group, greater energy intakes at breakfast and lower
      energy intakes during the evening were associated with a lower BMI. However, when
      diet records which produced unreasonably low energy intakes were removed from the
      analysis, these relationships disappeared except for energy intakes at breakfast
      and BMI in the Adolescent group. CONCLUSION: It is suggested that the
      relationship between feeding pattern and BMI observed in the Adolescent and
      Middle-aged groups was caused by underestimation of 'habitual' energy intake from
      snacks and the omission of breakfast by females and those who were overweight.
      The lack of relationship in the Working age group was attributed to the fact that
      more individuals in this group appeared to report valid diet records. Reported
      energy intake was directly related to BMI in the Working age group, but was not
      related to BMI in the other three age groups. It is concluded that feeding
      pattern is not a major factor in determining BMI in humans. Also, since snacks
      have a relatively high sugar and low fat composition compared with meals, it is
      suggested that biased under-reporting of snacks by the obese could produce
      spurious results from free-living studies which show that obesity is related to
      the proportion of energy from fat in the diet.

PMID- 8863012
TI  - Eating patterns in functional dyspepsia: a case control study.
AB  - OBJECTIVE: To determine whether eating patterns differ between patients with
      endoscopically determined functional dyspepsia and non-dyspeptic controls.
      DESIGN: Case-control study (50 per group). A seven-day record of food consumption
      with time of food consumption was determined. SETTING: Endoscopy clinic, St.
      James' Hospital and the Clinical Nutrition Laboratory at the Trinity College
      Medical School. MAIN OUTCOME MEASURES: Meal eating pattern and their temporal
      distribution; consumption of food categories and their temporal distribution;
      data for all subjects and for employed vs unemployed subjects. RESULTS: There was
      no evidence to suggest that the pattern of food and meal intake throughout the
      day was in any way influenced by endoscopically determined functional dyspepsia.
      CONCLUSION: The widely held belief that patients with functional dyspepsia eat
      differently to healthy controls to relieve or prevent symptoms of dyspepsia is
      not supported by these findings.

PMID- 8863013
TI  - Circadian patterns of total 24-h hydrogen and methane excretion in humans
      ingesting nonstarch polysaccharide (NSP) diets and the implications for indirect
      calorimetric and D2 18O methodologies.
AB  - OBJECTIVES: To quantify the relationship between substrate fermentation and total
      24-h H2 and CH4 excretion on mixed diets and to assess errors incurred in the
      calculation of energy expenditure and fuel selection by the exclusion of these
      gases from standard calculations. DESIGN AND SUBJECTS: Twelve healthy, lean men
      were studied over two consecutive dietary periods of 3 weeks. Measurements of
      total H2 and CH4 excretion were made during 24h within a whole body calorimeter.
      Subjects were fed a diet containing 16 g or 38 g of nonstarch polysaccharide
      (NSP) and 16 g or 19 g resistant starch (RS). Colonic fermentation was measured
      by balance techniques during the two dietary treatments. RESULTS: There was an
      inverse non-linear relationship between H2 and CH4 excretion on both diets (r2 =
      0.53; P < 0.001), but absolute excretion did not increase significantly as the
      intake of NSP and RS (from 28 +/- 3 and 48 +/- 4 g/day) increased. No
      relationship was found between daytime and 24-h measurements of H2 and CH4. H2
      and CH4 excretion introduces an error of less than 0.2% and 1% in calculations of
      energy expenditure and CO2 production from the standard human equations used in
      indirect calorimetric (IC) and doubly labelled water (DLW) methodologies
      respectively, and less than 2% in fuel utilisation calculated as % non-protein
      energy expenditure from IC. CONCLUSIONS: This study provides evidence that
      neither daytime nor total 24-h rates of H2 or CH4 excretion accurately predict
      degree of fermentation of NSP+RS in either individual subjects or groups of
      subjects, probably because of changes in the stochiometry of the fermentation
      process.

PMID- 8863014
TI  - Composition of platelet phospholipids after moderate consumption of red wine in
      healthy volunteers.
AB  - OBJECTIVE: To evaluate the effect of moderate consumption of red wine on
      composition of platelet phospholipids, discriminating the effect of alcohol from
      that of non-alcoholic components. DESIGN: A randomised crossover study. SETTING:
      The Department of Food Science and Technology, University of Milan. SUBJECTS:
      Eleven healthy male volunteers who were moderate drinkers. INTERVENTIONS: For
      three periods of 4 weeks, subjects drank three different beverages [320 ml of red
      wine (providing 30 g/day of alcohol), 30 g/day of alcohol diluted in 320 ml of
      clear fruit juice or 320 ml of dealcoholised red wine] during the two main meals.
      Each treatment was preceded by a period of 4 weeks of complete withdrawal from
      any alcoholic beverage. At the end of each period the fatty acid composition of
      individual phospholipids was determined on isolated platelets. RESULTS:
      Consumption for a period of 4 weeks of non-alcoholic components either from 320
      ml of red wine or from the same amount of dealcoholised red wine resulted in
      similar increases in polyunsaturated fatty acids in all phospholipid fractions of
      platelet, with the exception of sphingomyelin. No differences were detected when
      we compared the composition of phospholipids at the end of red wine and alcohol
      treatments with findings at the end of dealcoholised treatment and abstinence.
      CONCLUSIONS: The increase of polyunsaturated fatty acids in platelet
      phospholipids due to the non-alcoholic components of red wine suggests an
      antioxidant effect that could be relevant in justifying the protective effect of
      red wine shown in epidemiological studies.

PMID- 8863015
TI  - The influence of fat free mass on prediction of densitometric body composition by
      bioelectrical impedance analysis and by anthropometry.
AB  - OBJECTIVE: To examine the effect of varying size of fat free mass (FFM) on the
      precision and bias of body composition prediction by bioelectrical impedance
      analysis (BIA) from four equations of Segal et al (BIA-Segal), Gray et al (BIA
      Gray, Lukaski et al (BIA-Lukaski) and those from a manufacturer (BIA-EZC), by
      body mass index (BMI), and by skinfold methods with reference to estimation by
      densitometry. SUBJECTS: 73 men and 77 women aged 17-71 years, were measured for
      height, weight, FFM, bioelectrical impedance and age. RESULTS: BIA-Segal gave the
      highest precision (men: R2 = 83%, women: R2 = 75%) and the least bias (men: slope
      = 0.88; women: slope = 0.81) of all BIA methods. There were poorer precision (R2
      < or = 50%) and more bias (slope < 0.70) by BIA-Lukaski and BIA-EZC in both
      sexes, which were comparable to the simpler BMI method. The skinfold method gave
      R2 = 83% and slope = 0.84 in men and R2 = 61% and slope = 0.86 in women. Bland
      and Altman analysis showed BIA-Segal gave prediction of FFM within +/-6 kg of 95%
      confidence interval limit of agreement of that estimated by UWW in most subjects.
      Other BIA methods presented unacceptably large underestimates of up to 15-17 kg
      in FFM. CONCLUSIONS: The BIA-Segal provide the best predictions of the methods
      tested, but using BMI-or waist-specific equations may be more practical than the
      original BIA-Segal method, which BIA methods are affected by large FFM, and not
      better than anthropometric methods in predicting FFM.

PMID- 8863016
TI  - Subclinical beriberi polyneuropathy in the low income group: an investigation
      with special tools on possible patients with suspected complaints.
AB  - OBJECTIVE: To determine the prevalence rate of subclinical beriberi
      polyneuropathy (PNP) in the low income group and to present new methods for early
      detection. DESIGN: We conducted a prospective, randomized observational study on
      all patients from family members of non-PNP patients presenting to the outpatient
      neurologic clinic of the Dr Soetomo Hospital in 1989 in Surabaya, Indonesia.
      MATERIAL AND METHODS: The 53 group I patients belonged to the low income series,
      whereas the 56 group II patients were from the mid- and high-income groups. We
      analyzed their diets and determined their blood thiamine levels. Neurologic,
      internal, psychiatric as well as neurophysiologic examinations were performed on
      all patients. RESULTS: The prevalence rate of subclinical beriberi PNP of the
      apparently healthy subjects of the low income group was 66% compared with 12.5%
      among the mid and high income groups. The exposure odds ratio was 13.6 (95% Cl,
      2.78 to 8.04) indicating that the low income group ran a greater risk of
      developing beriberi PNP than the mid and high income groups. CONCLUSION: Most of
      our low income group patients had an inadequate diet, especially concerning
      deficient thiamine intake. Analysis of the diets revealed, that they were usually
      rich in carbohydrate especially steamed milled rice, whereas intake of fat and
      thiamine was low, protein was just sufficient. The calorie intake was marginal.
      Carbohydrate rich and non fat calories in the diet with low thiamine intake may
      provoke beriberi.

PMID- 8863017
TI  - Plasma vitamins A and E and red blood cell fatty acid profile in newborns and
      their mothers.
AB  - OBJECTIVE: In this work, we have measured the plasma vitamins A and E and red
      blood cell fatty acid profile in newborns and their mothers and have determined
      whether there are any relationships between maternal blood and cord blood for the
      nutrients measured. SETTING: The study was performed at the Chung Shan Memorial
      Hospital, Taichung, Taiwan. SUBJECTS: Twenty-nine pairs of mothers and their term
      infants. INTERVENTIONS: Maternal venous blood was collected in the first
      trimester and at delivery, and cord blood was collected at delivery. Plasma
      vitamin A and E levels were determined by high performance liquid chromatography
      and red blood cell fatty acid profile was estimated by gas chromatography.
      RESULTS: Mothers had significantly greater plasma vitamin A and E levels and
      vitamin E/total lipid than their term neonates did (P < 0.05). Maternal plasma
      vitamin E and vitamin E/total lipid were significantly greater in the first
      trimester than at delivery (P < 0.05). Red blood cell phospholipid oleate and
      linoleate were significantly greater in maternal red blood cell than in cord
      blood (P < 0.05), however, stearate and arachidonate were significantly greater
      in the cord blood than in the maternal blood (P < 0.05). Maternal vitamin E,
      vitamin E/total lipid, palmitate, linoleate, arachidonate and docosahexaenoate
      were found positively correlated to those in their neonates (P < 0.05).
      CONCLUSIONS: The results suggest that there is a relationship between maternal
      blood and cord blood for some nutrients. Therefore, the nutritional status of
      mothers may affect the nutritional outcome of their neonates.

PMID- 8863018
TI  - Socio-economic influences on gender inequalities in child health in rural
      Bangladesh.
AB  - OBJECTIVE: To investigate gender inequalities in child growth and nutritional
      status in relation to socio-economic status in Bangladesh. DESIGN: A 16-month
      longitudinal study of child growth measuring anthropometric and socio-economic
      status. SETTING: A rural area of Jamalpur district, northern Bangladesh.
      SUBJECTS: 1366 children from 2 to 6 years of age. METHODS: Child height and
      weight were measured monthly. Morbidity, food intake and health-seeking
      behaviours were assessed fortnightly. Multivariable analyses were performed on
      the growth and nutritional status of male and female children in relation to
      socio-economic factors including father's occupation, parental education, birth
      order and family size. RESULTS: There was no evidence of gender bias in farming
      and trading/employee households but landless female children had significantly
      poorer height-for-age (P < 0.001) and weight-for-age (P < 0.001) than their male
      counterparts. During a period of natural disaster, a statistically significant
      interaction was observed between father's occupation and sex (P < 0.05) such that
      the combination of being female and being landless was more detrimental to
      nutritional status than either variable alone. Over the following 16-months,
      catch-up-growth was apparent in landless female children who grew significantly
      more in height-for-age (P < 0.001) and weight-for-age (P < 0.001) than their male
      counterparts. CONCLUSIONS: Gender inequalities in health in Bangladesh varied
      significantly according to occupational status, such that the effect of sex was
      dependent upon occupation. These effects were statistically significant during
      the period of natural disaster but became insignificant as local conditions
      improved. This demonstrates both temporal and socio-economic variation in gender
      inequalities in health.

PMID- 8863019
TI  - Lack of influence of intestinal transit on oxidative status in premenopausal
      women.
AB  - OBJECTIVE: There are reasons for believing that diet can alter the risk of
      malignancy by alteration of the body's oxidative status. Intestinal contents and
      enterohepatically recirculated substances are influenced by intestinal transit
      rate. A low fibre diet has been linked to the increase in constipation seen in
      countries consuming a westernized diet, as well as to the aetiology of many
      diseases. We studied the effects of altering intestinal transit rates and of
      wheat bran on oxidative status. DESIGN: 40 premenopausal women were randomized to
      receive dietary supplements of wheat bran, senna or loperamide for the length of
      two menstrual cycles. Dietary records, whole gut transit time (WGTT) and plasma
      lipid peroxides, measured as TBARS (specifically malondialdehyde) were determined
      at the beginning and end of each intervention. SETTING: University department of
      Medicine, Bristol Royal Infirmary. RESULTS: 36 volunteers completed the study.
      WGTT increased in those receiving loperamide and decreased in those receiving
      senna. The decrease in WGTT was not significant in those receiving wheat bran.
      Diets did not change. There were no changes in TBARS, cholesterol, triglyceride
      or TBARS adjusted for cholesterol and triglyceride, during any intervention.
      CONCLUSIONS: Dietary supplementation with wheat bran and pharmacological
      alteration of intestinal transit had no influence on oxidative status or on
      plasma cholesterol or triglycerides.

PMID- 8863020
TI  - Existence of iodine deficiency in Hong Kong--a coastal city in southern China.
AB  - OBJECTIVE: Iodine deficiency is a serious public health problem worldwide which
      is associated with mental retardation and cretinism. In view of a high incidence
      of transient neonatal hypothyroidism and a relatively high mean cord blood
      thyrotropin (TSH) concentration, a pilot study was carried out to analyse the
      urine iodine excretion in Hong Kong, a coastal city in the southern part of
      China. DESIGN: Early morning urine was collected from healthy volunteers
      including children (n = 104), adults (n = 112) and elderly subjects (n = 349). A
      semi-quantitative questionnaire survey on the pattern of food intake was
      conducted in the adults and elderly. RESULTS: 45.3% of the children, 51.7% of the
      adults and 55.3% of the elderly had urine iodine concentration below the criteria
      for iodine sufficiency (< 0.79 mumol/l). Iodine content in the drinking water and
      salt was low. A dietary survey revealed that seafood was not commonly consumed.
      50-80% of the subjects never consumed high-iodine containing food such as
      seaweed, kelp or laver, and only 50% consumed seawater fish daily. CONCLUSION: We
      confirmed that although Hong Kong is a non-goitrous area, iodine insufficiency
      exists. It is unsafe to assume that iodine deficiency does not exist in coastal
      urban areas.

PMID- 8863021
TI  - Tibial plafond fractures: limited internal fixation and a hybrid external
      fixator.

PMID- 8863022
TI  - Analysis of failed surgical management of fractures of the base of the fifth
      metatarsal distal to the tuberosity: the Jones fracture.
AB  - Failure of surgical management of fractures of the base of the fifth metatarsal
      distal to the tuberosity is uncommon. Only one such failure has been reported in
      the literature to date. The purpose of this article is to present the clinical
      course of 11 patients with failure of surgically managed jones fractures reviewed
      by the senior author (J.S.T.). Surgical management was complicated by delayed
      union in three patients, refracture in seven patients, and nonunion in one
      patient. The 11 procedures were divided between two established techniques: (1)
      intramedullary screw fixation (N = 6) and (2) inlaid corticocancellous bone graft
      (N = 5). In the six intramedullary fixation procedures, using other than a 4.5-mm
      ASIF malleolar screw for internal fixation correlated with failure. In the five
      inlaid bone graft procedures, undersized corticocancellous grafts and incomplete
      reaming of the medullary canal correlated with failure. Also, after both
      procedures, early return to vigorous physical activity is believed to have played
      a role in delayed union and refracture.

PMID- 8863023
TI  - Distal soft tissue release using direct and indirect approaches: an anatomic
      study.
AB  - Two surgical approaches for distal soft tissue release in the correction of
      hallux valgus, one using a dorsal first web space incision and the other a
      longitudinal medial capsulotomy incision (used also for medial eminence
      resection), were studied to compare and delineate the structures actually
      incised. Anatomic dissections were performed on six fresh-frozen amputation
      specimens using each of the approaches. The adequacy of release of the adductor
      hallucis, transverse and oblique heads, first metatarsophalangeal lateral
      capsule, and suspensory ligament was reviewed. Any inadvertent damage to the
      first metatarsal head cartilage, second metatarsophalangeal capsule, and lateral
      head of the flexor hallucis brevis tendon was also noted. Distal soft tissue
      release is thought to be an important part of hallux valgus surgery. Based on our
      anatomic dissections, the actual extent of the release may be inconsistent and
      unpredictable, and may have implications for the predictability of results after
      hallux valgus surgery.

PMID- 8863024
TI  - Plantar pressure measurements during ambulation in weightbearing conventional
      short leg casts and total contact casts.
AB  - Total contact casts have been shown to be effective in healing plantar
      neuropathic ulcerations. The proposed mechanism of action is reduction of
      pressure over the ulcer during ambulation. However, there is little information
      to support this contention. Plantar pressure distribution was studied using
      standard short leg casts and total contact casts in normal feet. Both types of
      casts reduced forefoot pressure in study subjects. This occurred because of an
      increase in plantar surface area exposed to weightbearing forces. While increased
      force was shifted to the midfoot, there was no increase in pressure due to a
      corresponding increase in midfoot surface area exposed to this force. No
      significant difference was noted between standard short leg casts and total
      contact casts.

PMID- 8863025
TI  - Plantar pressure analysis of diabetic rockerbottom deformity in total contact
      casts.
AB  - In a previous study, we examined plantar pressures under normally arched
      individuals in casts. The investigation described in this article was designed to
      assess plantar pressure distribution in subjects with Charcot midfoot collapse
      and rockerbottom deformity in standard short leg casts and total contact casts.
      Our results show that both types of casts significantly reduced midfoot
      pressures. No significant differences were noted between the two casting groups.

PMID- 8863026
TI  - Quantitative analysis of cancellous bone graft available from the greater
      trochanter.
AB  - To quantify the amount of cancellous bone graft available from the greater
      trochanteric region, 20 paired iliac crest-proximal femur specimens were
      harvested and compared in 10 adult pelvises. A 1.3 x 1.3-cm cortical window was
      made in the lateral aspect of the proximal femur 2 cm distal from the tip of the
      greater trochanter. Cancellous bone evacuation was performed by curettage. The
      extent of harvest was mechanically limited by the medial wall of the trochanter
      and by curette impingement on the margins of the cortical window. The graft was
      quantitated after maximal digital compression in a 10-ml syringe and compared
      with cancellous graft obtained from the paired anterior iliac crest. The average
      compressed volume of cancellous bone harvested from the greater trochanter was
      6.5 ml (range, 4.2-9.6 ml). The average iliac crest cancellous bone volume was
      6.0 ml (range, 2.7-8.8 ml). Differences in graft volume between the anterior
      iliac crest and the trochanter were not statistically significant. The resulting
      defect in the proximal femur remained isolated to the trochanteric region. In
      this study, we demonstrate that cancellous bone is available from the greater
      trochanteric region in an amount similar to that available from the anterior
      iliac crest. We also show that it is obtainable in a reproducible manner. Our
      clinical experience of over 100 cases has demonstrated acceptable morbidity
      associated with this technique. The greater trochanteric region may be used as a
      secondary source of autogenous cancellous bone graft when specific procedures
      demand more bone graft than available from the iliac crest alone, or in patients
      who have had previous iliac crest graft harvest.

PMID- 8863027
TI  - A study of intrinsic factors in patients with stress fractures of the tibia.
AB  - We aimed to study intrinsic factors in 29 consecutive patients with well
      documented unilateral stress fractures of the tibia. Anthropometry, range of
      motion, isokinetic plantar flexor muscle performance, and gait pattern were
      analyzed. The uninjured leg served as the control. A reference group of 30
      uninjured subjects was compared regarding gait pattern. Anterior stress fractures
      of the tibia (N = 10) were localized in the push-off/ landing leg in 9/10
      athletes, but were similarly distributed between legs in posteromedial injuries
      (N = 19). Ten (30%) of the stress fracture subjects had bilateral high foot
      arches, similar to those found in the reference group. There were no other
      systematic differences in anthropometry, range of motion, gait pattern, or
      isokinetic plantar flexor muscle peak torque and endurance between injured and
      uninjured legs. No other differences were found between anterior and
      posteromedial stress fractures. We conclude that anterior stress fractures of the
      tibia occur mainly in the push-off/landing leg in athletes. Within the
      limitations of our protocol, no registered intrinsic factor was found to be
      directly associated with the occurrence of a stress fracture of the tibia.

PMID- 8863028
TI  - Parent satisfaction comparing two bandage materials used during serial casting in
      infants.
AB  - Plaster of Paris was compared with semirigid fiberglass casting material during
      serial casting in 17 infants with clubfoot or rigid metatarsus adductus.
      Semirigid fiberglass was statistically superior in its durability, convenience,
      performance, and ease of removal. The average amount of time for home cast
      removal by the parents was 55 minutes for plaster of Paris and 21 minutes for
      semirigid fiberglass. Complications such as skin abrasions and cast slip-off were
      similar for both casting materials. Ninety-four percent of parents strongly
      preferred semirigid fiberglass rather than plaster of Paris for their child's
      serial casting.

PMID- 8863029
TI  - Aneurysmal bone cyst and giant cell tumor of the foot.
AB  - From 1950 to 1994, 257 cases of benign bone tumors of the foot were treated at
      the Bone Tumor Center of the Rizzoli Institute. Aneurysmal bone cysts (ABC) and
      giant cell tumors (GCT) are rare and often they are misdiagnosed. To define the
      clinical and radiographic features useful for diagnosis, x-rays of 24 ABCs and 21
      GCTs of the foot were reviewed. Adding our series to the cases reported in the
      literature, the only important clinical data that emerged was the average age of
      patients affected by ABC and GCT (15 and 27 years, respectively). ABCs localized
      in small tarsal bones were rare (6%), whereas 19% of GCTs were found in this
      site. The eccentric, round shape of a lytic lesion was more characteristic of
      GCT. An aggressive pattern of radiographic bone destruction was observed more
      frequently in GCT than in ABC (P = 0.01). Septation was seen in both tumors.
      Typical of ABC was a sharp and trabeculated margin, whereas GCT had an ill
      defined edge with normal cancellous bone (P = 0.007). The growth of ABCs often
      expanded the cortex, while GCTs eroded, thinned, and broke the cortical bone (P =
      0.001). A saucerized cortex was observed only in ABCs. A bony shelf was more
      characteristic of ABC than of GCT (P = 0.002). Pathologic fractures (67%) and
      joint involvement, evaluated by computed tomography and magnetic resonance
      imaging (83%), were more frequent in GCTs, whereas fluid levels were more
      frequently observed in ABCs (47%). The majority of the tumors were stage 2, but
      GCTs represented 70% of stage 3 aggressive lesions.

PMID- 8863030
TI  - Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a
      case report and literature review.
AB  - Fluoroquinolone antibiotics (such as olprofloxacin, pefloxacin, ofloxacin,
      norfloxacin, temafloxacin, etc.) have recently been implicated in the etiology of
      Achilles tendinitis and subsequent tendon rupture. We report on a patient with
      bilateral partial Achilles tendon ruptures associated with ciprofloxacin therapy
      and present a review of the current literature on this increasingly recognized
      complication. Treatment with fluoroquinolones should be discontinued at the first
      sign of tendon inflammation so as to reduce the risk of subsequent rupture.
      Magnetic resonance imaging is useful in distinguishing between Achilles
      tendinitis and partial tendon rupture.

PMID- 8863031
TI  - The subtalar angle: a proposed measure of rearfoot structure.
AB  - The purpose of this study was to propose a new measure of rearfoot structure to
      further enhance the understanding of the function of the foot. Landmarks visible
      on sagittal plane radiographs were used to represent the approximate direction of
      the subtalar joint axis in the sagittal plane based upon descriptions from the
      literature of its orientation. Four landmarks were chosen, resulting in four
      calculated angles. One hundred lateral view radiographs were analyzed. The mean
      values ranged from 28.7 degrees to 47.7 degrees. These values are within the
      ranges reported from both cadaver and in vivo studies. Tests of repeatability of
      the measures resulted in intraclass coefficient values between 0.94 and 0.98,
      suggesting good reliability. All four angles correlated highly among each other
      (r = 0.88-0.97). Examination of the validity of any one of these measures is left
      to those who are able to accurately calculate the orientation of the subtalar
      joint axis.

PMID- 8863032
TI  - A pitfall of coronal computed tomographic imaging in evaluation of calcaneal
      fractures.
AB  - Computed tomographic (CT) coronal images of the posterior talocalcaneal joint
      were compared with lateral radiographic views and intraoperative findings in 35
      patients with 36 intra-articular calcaneal fractures. The severity of articular
      incongruity and rotational displacement of the posterior facet fragment were not
      well appreciated in coronal CT images of nine patients, although Bohler and
      Gissane angles were significantly decreased in lateral radiographs. This
      disparity between the radiographic and coronal CT scans can be explained by the
      intraoperative finding of rotation of the fractured central or lateral portion of
      the convex posterior calcaneal facet along a horizontal axis in the coronal
      plane.

PMID- 8863033
TI  - The Foot Function Index for measuring rheumatoid arthritis pain: evaluating side
      to-side reliability.
AB  - The Foot Function Index is a validated and reliable instrument for measuring foot
      pain, disability, and activity restriction in patients with rheumatoid arthritis.
      For the purposes of orthopaedic studies in which one foot serves as an internal
      control, we assessed the side-to-side reliability of the seven-question Foot
      Function Index pain subscale. Thirty patients with rheumatoid arthritis completed
      visual analog scale pain questionnaires for both feet on two occasions 8 days
      apart. Internal reliability of the scale was high, with Cronbach's alphas ranging
      from 0.94 to 0.96, suggesting good left versus right discriminatory abilities.
      Principal component factor analysis segregated the questions into two large
      clusters containing predominantly either left or right foot items. Intraclass
      correlation coefficients were examined for test-retest reliability (separated by
      side) and for side-to-side reliability (separated by the day of test). The
      resultant intraclass correlation coefficients were nearly equivalent, ranging
      from 0.79 to 0.89. Generalizability analysis yielded similar results. Intraclass
      correlation coefficients and generalizability analysis demonstrate that the
      majority of variation is best explained by the differences within subjects or
      between subjects rather than by test-retest or side-to-side differences. We
      recommend the Foot Function Index as a reliable measurement scale for use in
      orthopaedic interventional trials.

PMID- 8863034
TI  - The approach to stool examination for parasites.
AB  - This article presents the sequences followed in order to maximize the yield of
      laboratory assistive diagnosis of parasitic infections in the physiologic passage
      and/or collection of specimens for those parasites producing pathologic disease
      in the gastrointestinal tract and liver. The advantages and disadvantages of the
      many methods available to the clinician and laboratorian in the examination of
      those specimens are presented in a work-flow mode. The controversy relative to
      the current practice of controlling unwarranted specimen submission and the
      reasons for their rejection of limited examination and interpretation are
      discussed. Quality assurance and safety practices are also addressed.

PMID- 8863035
TI  - Preparing the international traveler.
AB  - Travelers to developing countries are at risk for diseases ranging from
      traveler's diarrhea to malaria. Immunizations, medications, and sensible
      precautions can ensure a safe trip in most areas of the world. This article
      presents an overview of how to prepare the international traveler.

PMID- 8863036
TI  - Protozoa. Amebiasis.
AB  - The intestinal protozoan parasite Entamoeba histolytica causes amebic dysentery
      and amebic liver abscess, and ranks third worldwide among parasitic causes of
      death. The application of molecular techniques to the study of this organism have
      led to major advances in understanding the pathophysiology of amebic infection.
      This article reviews what is currently known about the pathogenesis, clinical
      manifestations, diagnosis, and treatment of amebiasis.

PMID- 8863037
TI  - Giardiasis.
AB  - Despite rapid progress in understanding the biology of Giardia, several questions
      remain unanswered. First, there is no adequate explanation for the diverse
      clinical spectrum of giardiasis. Second, the mechanisms by which Giardia produces
      diarrhea and malabsorption are poorly understood, although some progress has been
      made. Finally, despite extensive studies in animal models and human infections,
      the key immunologic determinants for clearance of acute infection and development
      of protective immunity remain ill defined. This article discusses the
      epidemiology, pathology, diagnosis, treatment, and prevention of giardiasis.

PMID- 8863038
TI  - American trypanosomiasis (Chagas' disease).
AB  - Gastrointestinal dysfunction is a major problem for many patients with chronic
      Chagas' disease, as are cardiac dysrhythmias and cardiomyopathy. The underlying
      anatomic abnormality in these patients is a denervation of the gastrointestinal
      tract. This process of nerve destruction usually develops insidiously over many
      years, and it is highly variable in terms of its extent in individual patients as
      well as in the segments of the gastrointestinal tract that are most affected.
      Megaesophagus is the most common manifestation of gastrointestinal Chagas
      disease, and mechanical dilation of the esophageal sphincter or surgery in
      advanced cases usually give satisfactory relief of symptoms. Megacolon,
      particularly of the sigmoid segment, is also common in patients with chronic T.
      cruzi infections, and its presence can be complicated by fecal impaction or
      sigmoid volvulus. Patients with advanced megacolon who have resections of the
      sigmoid colon and most of the rectum generally do well postoperatively.

PMID- 8863039
TI  - Visceral leishmaniasis.
AB  - Visceral leishmaniasis presents a serious problem in endemic regions that is
      difficult to treat or prevent. Several epidemiologic problems make the disease
      particularly troublesome to manage. These include the facts that classic visceral
      leishmaniasis is fatal if untreated and there is not reliable access to medical
      care in many endemic regions. When available, treatment has associated toxicity
      and requires the use of intravenous medications with careful monitoring for
      toxicity, which are complex to administer in underdeveloped nations. There is an
      increasing incidence of the disease in HIV-infected individuals in southern
      Europe, in part because of the fact that eradication of the organism from
      infected persons using currently available drugs appears to be difficult if not
      impossible. Furthermore, chronic cutaneous forms of the disease allow humans and
      animals to maintain the organism long-term in a bodily site that is easily
      accessible to the sandfly vector. More effective and less toxic treatment
      modalities as well as a protective vaccine are badly needed to manage this
      disease.

PMID- 8863040
TI  - Ascariasis.
AB  - Ascariasis is a helminthic infection of global distribution with more than 1.4
      billion persons infected throughout the world. The majority of infections occur
      in the developing countries of Asia and Latin America. Of 4 million people
      infected in the United States, a large percentage are immigrants from developing
      countries. Ascaris-related clinical disease is restricted to subjects with heavy
      worm load, and an estimated 1.2 to 2 million such cases, with 20,000 deaths,
      occur in endemic areas per year. More often, recurring moderate infections cause
      stunting of linear growth, cause reduced cognitive function, and contribute to
      existing malnutrition in children in endemic areas. Ascaris infection is acquired
      by the ingestion of the embryonated eggs. The larvae, while passing through the
      pulmonary migration phase for maturation, cause ascaris pneumonia. Intestinal
      ascaris is usually detected as an incidental finding. Ascaris-induced intestinal
      obstruction is a frequent complication in children with heavy worm loads. It can
      be complicated by intussusception, perforation, and gangrene of the bowel. Acute
      appendicitis and appendicular perforation can occur as a result of worms entering
      the appendix. HPA is a frequent cause of biliary and pancreatic disease in
      endemic areas. It occurs in adult women and can cause biliary colic, acute
      cholecystitis, acute cholangitis, acute pancreatitis, and hepatic abscess. RPC
      causing hepatic duct calculi is possibly an aftermath of recurrent biliary
      invasion in such areas. Ultrasonography can detect worms in the biliary tract and
      pancreas and is a useful noninvasive technique for diagnosis and follow-up of
      such patients. ERCP can help diagnose biliary and pancreatic ascariasis,
      including ascaris in the duodenum. Also, ERCP can be used to extract worms from
      the biliary and pancreatic ducts when indicated. Pyrantel pomoate, mebendazole,
      albendazole, and levamisole are effective drugs and can be used for mass therapy
      to control ascariasis in endemic areas.

PMID- 8863041
TI  - Enterobius, trichuris, capillaria, and hookworm including ancylostoma caninum.
AB  - Infections by the nematodes Enterobius, Trichuris, Capillaria, and hookworm are
      some of the most widespread gastrointestinal infections worldwide. This article
      is designed not only to provide an overview of the different parasites in terms
      of epidemiology, clinical manifestation, and disease but also to highlight
      particular areas of intensive research activity that are providing new insights
      into both the biology of the host-parasite relationship and possible new
      approaches to infection management for the future.

PMID- 8863042
TI  - Schistosomiasis. Pathophysiology, diagnosis, and treatment.
AB  - Globally, schistosomes infect 1 in 30 people. Tourists travel to endemic areas,
      whereas students, workers, and expatriates travel to nonendemic areas. Physicians
      around the world need to remain aware of this common parasitic infection.
      Pathology results from parasite eggs that lodge in the intestines and liver.
      Intestinal schistosomiasis is most often asymptomatic and presents with occult
      gastrointestinal bleeding. Hepatosplenic schistosomiasis develops insidiously
      because of cumulative fibrotic injury. Stigmata of liver failure are absent
      unless comorbid viral or alcoholic hepatitis is present. Patients with end-stage
      hepatosplenic schistosomiasis die from variceal hemorrhage. Diagnosis of
      schistosomiasis is confirmed by finding eggs in stool or biopsy specimens.
      Antischistosome antibodies may identify infected tourists returning from endemic
      areas. Circulating schistosome antigens distinguish current from past infections.
      Praziquantel is the schistosomicidal drug of choice. Most cases of hepatosplenic
      schistosomiasis resolve after effective treatment. Prophylactic propranolol may
      prevent hemorrhage in praziquantel-treated patients with high-grade varices.
      Sclerotherapy is also efficacious. When necessary, patients with hepatosplenic
      schistosomiasis tolerate decompressive surgery well.

PMID- 8863043
TI  - Liver and intestinal flukes.
AB  - A number of trematodes besides schistosomes parasitize humans and domesticated
      animals. Although they do not have as great a public health impact as
      schistosomiasis, they are prevalent in Southeast Asia as well as among the
      greater than 1 million immigrants from this region to North America. The human
      biliary flukes include C. sinensis, O. viverrini, and O. felineus. These chronic
      infections are often asymptomatic but over time may cause biliary thickening,
      cholangitis, and a predisposition to cholangiocarcinoma. Zoonotic trematode
      infections include the sheep liver fluke F. hepatica and the intestinal flukes
      Fasciolopsis, Echinostoma, Heterophyes, and Metagonimus.

PMID- 8863044
TI  - Tapeworms (cestodiasis).
AB  - Nearly all of the cestodes, or tapeworms (class Cestoda in the phylum
      Platyhelminthes, the flatworms), are parasitic as adults in the intestinal tract
      of vertebrates. This article discusses the epidemiology, diagnosis, and treatment
      of taeniasis, diphyllobothriasis, hymenolepiasis, dipylidiasis, and other
      tapeworm infections.

PMID- 8863045
TI  - Cestodes. Echinococcus.
AB  - This article deals with cystic echinococcosis (CE) and alveolar echinococcosis in
      humans caused by the cestode parasites Echinococcus granulosus and Echinococcus
      multilocularis. The life cycles of these parasites and their epidemiologic
      aspects are briefly discussed, and a detailed review is presented on clinical
      aspects of the diseases, including diagnosis and therapy. Considerable progress
      has been made in chemotherapy but the results are not yet satisfactory. A new
      alternative for treatment of CE is puncture of cysts, aspiration of fluid,
      injection of ethanol, and reaspiration of fluid (PAIR).

PMID- 8863046
TI  - Parasitic diseases in immunocompromised hosts. Cryptosporidiosis, isosporiasis,
      and strongyloidiasis.
AB  - Cryptosporidiosis and isosporiasis are intestinal infections caused by the
      protozoan parasites Cryptosporidium parvum and Isospora belli, respectively. HIV
      infection and other immunodeficiency diseases predispose human subjects to severe
      and prolonged cryptosporidiosis. There is also evidence that HIV infection
      predisposes to chronic isosporiasis. Strongyloidiasis is caused by a nematode
      worm, Strongyloides stercoralis. Administration of corticosteroids to patients
      with chronic low-grade S. stercoralis infection can trigger a fulminant, life
      threatening form of strongyloidiasis.

PMID- 8863048
TI  - Laminins, tenascin and type VII collagen in colorectal mucosa.
AB  - The distribution of different laminin polypeptides, type VII collagen and
      tenascin has been studied in adult and foetal colorectal mucosa by using the
      indirect immunofluorescence technique. Immunoreactivity for laminin alpha 1 chain
      was located to basement membranes of epithelia, muscularis mucosae, and blood
      vessels, respectively in different segments of adult colon and rectum. Laminin
      beta 1 and gamma 1 chains were additionally expressed in lamina propria. Laminin
      alpha 2 chain was also found in lamina propria around the pericryptal
      fibroblasts. Immunoreactivity for laminin beta 2 chain was restricted to basement
      membranes in the muscularis mucosae and arteries. Laminin alpha 3 and beta 3
      chains, suggestive for laminin-5, were confined especially to surface epithelial
      basement membranes. Immunoreactivity for type VII collagen was confined to
      basement membrane of surface epithelium in a punctate manner, while that for
      tenascin was seen slightly more broadly in the basement membrane zone and also in
      the muscular layer. The distribution of laminin chains in 16-week-foetal colon
      mostly resembled that of corresponding adult tissue, although immunoreactivities
      for laminin alpha 2 and beta 2 chains were lacking. Type VII collagen and the
      high molecular weight isoform of tenascin were also absent from the foetal colon.
      The results show that the basement membrane of the surface epithelium of colon
      and rectum express the components of epithelial adhesion complex, laminin-5
      (alpha 3-beta 3-gamma 2) and type VII collagen, resembling in this respect small
      intestine and stomach while laminin-2 (alpha 2-beta 1-gamma 1) appears to be
      associated with pericryptal fibroblasts, and laminin-1 (alpha 1-beta 1-gamma 1)
      widely in most basement membranes.

PMID- 8863049
TI  - Localization of the mRNA encoding the zona protein ZP3 alpha in the porcine
      ovary, oocyte and embryo by non-radioactive in situ hybridization.
AB  - The mRNA of the zona pellucida glycoprotein ZP3 alpha was localized in frozen
      sections of pig ovaries, isolated oocytes and early embryos by in situ
      hybridization using biotinylated oligonucleotide probes. In follicles, the
      distribution of mRNA for ZP3 alpha was correlated with the developmental stage:
      in primordial and primary follicles, the mRNA was shown to be predominantly
      localized in the oocyte. In secondary follicles, mRNA was found in both the
      oocyte and follicle cells. In tertiary and preovulatory follicles, the follicle
      cells showed distinct staining, whereas the oocyte was labelled weakly. In the
      early embryo, i.e. 2 days after fertilization, mRNA for ZP3 alpha could not be
      demonstrated. Our results suggest that, in the pig, the zona pellucida protein
      ZP3 alpha is synthesized by the oocyte and the follicle cells in sequence. After
      fertilization, synthesis of ZP3 alpha is terminated.

PMID- 8863050
TI  - Immunohistochemical localization of oviductin in the endometrial lining of the
      golden hamster (Mesocricetus auratus) during the estrous cycle and early
      gestation.
AB  - Oviductal non-ciliated secretory epithelial cells, under hormonal stimulation,
      synthesize and secrete a family of glycoproteins referred to as oviductins. These
      glycoproteins are found in oviductal fluid in several mammalian species, and have
      been localized in the oviduct, and in the zona pellucida of ovulated oocytes. In
      the golden hamster, this glycoprotein is named hamster oviductin-I. Recently, an
      immunofluorescent study on hamster uterine tissue has revealed the presence of
      the glycoprotein in luminal epithelial cells in a heterogeneous labelling pattern
      during the estrous cycle. The mechanism of endometrial epithelial cell
      receptivity to hamster oviductin-1 is not known. In this study,
      immunohistochemical studies were performed using a monoclonal antibody against
      the oviductin in conjunction with silver enhancement technique, in an attempt to
      determine further the factors playing a role in uterine receptivity to oviductin
      1. Paraffin sections of hamster uterus obtained from different stages of the
      estrous cycle and from days 1-6 of gestation, and paraffin sections of hamster
      oviduct obtained from days 1-6 of gestation were used in this study. The results
      we obtained using the silver enhancement technique show that hamster uterus
      luminal epithelial cells exhibit a homogeneous, high intensity immunolabelling
      pattern throughout the estrous cycle, whereas, during gestation, labelling
      intensity decreases as the period for blastocyst implantation approaches. Oviduct
      epithelial cells revealed no definite fluctuating pattern in immunolabelling
      intensities during gestation, indicating no change in synthesis and secretion of
      the glycoprotein during this period. It is speculated that receptors for hamster
      oviductin-1 are present at the apical cell surface of endometrial cells and that
      implantation of the developing blastocyst into the uterine wall is possible only
      following downregulation of these receptors. The use of the silver enhancement
      technique proves to be an effective tool in immunohistochemical studies at the
      light microscope level, as seen through this study.

PMID- 8863051
TI  - Simultaneous detection of cytokine and immunophenotype at the single cell level
      by immunoenzymatic double staining.
AB  - The goal of this study was to establish a generally applicable immunoenzymatic
      method for the simultaneous detection of cytokine and immunophenotype at the
      single cell level. Evaluating various cell preparations and staining protocols,
      we found that permeabilization by saponin (0.1%) is very efficient, in
      combination with glutaraldehyde (0.04%) as fixative. Among various staining
      procedures, sequential immunoperoxidase labelling of the cytokine by use of
      diaminobenzidine, and detection of the immunophenotype by use of 4-chloronaphthol
      proved most discriminative. The typical localization of the cytokine reaction
      product ('Golgi staining') within the cell, and the 'ring-like' staining for the
      immunophenotype on the cell surface, allowed precise identification of double
      labelled cells. Primary monoclonal antibodies from the same species could be used
      without loss of sensitivity and specificity for either or both antigens. This
      method thus provides the opportunity to study morphology, cytokine and
      immunophenotype simultaneously at the single cell level with standard equipment.
      Its application for the analysis of tissue samples is in progress, and may allow
      us to incorporate the cytokine-type as a new parameter in histopathological
      diagnostics.

PMID- 8863052
TI  - Hepatotoxicity of N, N-dimethylformamide (DMF) in acute poisoning with the
      veterinary euthanasia drug T-61.
AB  - 1. We report on a patient who was resuscitated after a suicide attempt with the
      veterinary euthanasia product T-61 and treated with N-acetylcysteine (NAC) to
      prevent hepatotoxicity from N,N-dimethylformamide (DMF), the solvent of T-61. 2.
      Serum concentrations of DMF were high as compared with values published on
      occupational exposure. 3. The patient showed only a transient increase in liver
      enzymes with eventually a full recovery. 4. The hepatoprotective effect of NAC
      was studied in a rat model using the rise in serum sorbitol dehydrogenase (SDH)
      as a marker for DMF-induced hepatotoxicity. 5. Four series of randomized,
      controlled and double-blind experiments were carried out and consistently showed
      a lower increase in SDH in NAC-treated animals in each series. The difference was
      statistically significant only when the data of the 4 series were pooled. This is
      probably due to the large interindividual variations in the effect of DMF. 6. We
      hypothesize that in the rat NAC may have a protective effect. Whether NAC is also
      protective in patients, in which it is administered after exposure to DMF, cannot
      be concluded from the present experiments.

PMID- 8863047
TI  - In situ heterogeneity of peroxisomal oxidase activities: an update.
AB  - Oxidases are a widespread group of enzymes. They are present in numerous
      organisms and organs and in various tissues, cells, and subcellular compartments,
      such as mitochondria. An important source of oxidases, which is investigated and
      discussed in this study, are the (micro)peroxisomes. Oxidases share the ability
      to reduce molecular oxygen during oxidation of their substrate, yielding an
      oxidized product and hydrogen peroxide. Besides the hydrogen peroxide
      catabolizing enzyme catalase, peroxisomes contain one or more hydrogen peroxide
      generating oxidases, which participate in different metabolic pathways. During
      the last four decades, various methods have been developed and elaborated for the
      histochemical localization of the activities of these oxidases. These methods are
      based either on the reduction of soluble electron acceptors by oxidase activity
      or on the capture of hydrogen peroxide. Both methods yield a coloured and/or
      electron dense precipitate. The most reliable technique in peroxisomal oxidase
      histochemistry is the cerium salt capture method. This method is based on the
      direct capture of hydrogen peroxide by cerium ions to form a fine crystalline,
      insoluble, electron dense reaction product, cerium perhydroxide, which can be
      visualized for light microscopy with diaminobenzidine. With the use of this
      technique, it became clear that oxidase activities not only vary between
      different organisms, organs, and tissues, but that heterogeneity also exists
      between different cells and within cells, i.e. between individual peroxisomes. A
      literature review, and recent studies performed in our laboratory, show that
      peroxisomes are highly differentiated organelles with respect to the presence of
      active enzymes. This study gives an overview of the in situ distribution and
      heterogeneity of peroxisomal enzyme activities as detected by histochemical
      assays of the activities of catalase, and the peroxisomal oxidases D-amino acid
      oxidase, L-alpha-hydroxy acid oxidase, polyamine oxidase and uric acid oxidase.

PMID- 8863053
TI  - Reference values for young normal Sprague-Dawley rats: weight gain, hematology
      and clinical chemistry.
AB  - 1. Arterial blood from 63 male (315-500 g) and 60 female (210-290 g) healthy
      Sprague-Dawley rats was analyzed for 16 hematological and 22 clinical chemistry
      parameters. 2. Nine of these parameters were associated with growth and
      developmental changes in males between 38-78 days and females 49 - 89 days of
      age. 3. Weight gain in both sexes followed patterns consistent with other studies
      using this strain, but interexperimental variation was as much as +/-22%. 4.
      Rectal temperatures of females averaged 37.28 degrees C, being statistically
      greater (P < 0.05) than the average male at 36.99 degrees C. 5. The data provide
      reference values for use in toxicological and other investigations.

PMID- 8863054
TI  - Paraphenylenediamine induced optic atrophy following hair dye poisoning.

PMID- 8863055
TI  - The effect of sulphur mustard on glutathione levels in rat lung slices and the
      influence of treatment with arylthiols and cysteine esters.
AB  - 1. Sulphur mustard reacts directly with benzenethiols and cysteine esters in
      aqueous medium. 2. Benzenethiols diffuse into lung slices in short term culture.
      3. Treatment of lung slices in short term culture with benzenethiols does not
      protect cellular glutathione from conjugation with sulphur mustard. 4. Following
      uptake of cysteine ester into lung slices cysteine is elevated but this does not
      protect cellular glutathione from sulphur mustard.

PMID- 8863057
TI  - Respiratory toxicity of direct lytic factor in the venom of the southern Chinese
      cobra (N. naja atra) in dogs.
AB  - The effects of direct lytic factor (DLF) on respiratory ventilation, gas exchange
      as well as hemodynamics were studied in anesthetized dogs. After an intravenous
      DLF dose of 1 mg/kg, the initial manifestation of intoxication was observed as
      follows: (1) Increase in airway impedance characterized by slowed air flow rate
      and increased negative transpulmonary pressure. (2) Decrease in dynamic
      compliance. (3) Progressive increase in venoarterial shunt (Qs/Qt) and decrease
      in PaO2, (4) Elevation of pulmonary artery blood pressure and fall of mean
      systemic blood pressure and maximal left ventricular pressure. Above actions
      reached the peak values at 15 min and thereafter all respiratory functional
      parameters, except Qs/Qt and hypoxemia, returned gradually to approach the normal
      levels at 50 min. The tidal volume, PaCO2 and LVEDP remained unchanged until
      another DLF dose of 1.5 mg/kg was given. After a second dose of DLF (total 2.5
      mg/kg), the respiratory functions and the cardiac performance deteriorated as
      follows: (1) Further increase in Qs/Qt and hypoxemia. (2) Appearance of
      hypercapnea and acidosis. (3) Fall of dP/dtmax and elevation of LVEDP, widening
      of QRS complex of ECG. (4) Blood pressure run a downhill course. From above
      experimental evidence, we came to the conclusion that as well as the basic
      cardiotoxicity, respiratory toxicity of DLF must be considered as the primary,
      because of broad spectrum of action of DLF and early effect on respiratory
      function.

PMID- 8863056
TI  - Combined dapsone and clofazimine intoxication.
AB  - We report clinical findings and pharmacokinetic data regarding a combined dapsone
      and clofazimine intoxication in a man, who ingested 50 tablets of dapsone (100
      mg) 20 capsules of clofazimine (100 mg) and two tablets of rifampicin (600 mg).
      Oral administration of activated charcoal (50 grams) and sodium sulphate (20
      grams) after gastric lavage resulted in an elimination half-life in plasma of
      11.1 and 10.8 h for dapsone and its main metabolite, monoacetyldapsone,
      respectively. A rapid initial decrease of the plasma concentration of clofazimine
      was observed after gastric lavage and administration of activated charcoal and
      sodium sulphate. 15 h after this treatment, clofazimine plasma levels remained
      relatively constant. Dapsone-induced methaemoglobinaemia (48% at admission) was
      treated successfully with methylene blue.

PMID- 8863058
TI  - Environmental endocrine modulators--where toxicology meets epidemiology.

PMID- 8863059
TI  - Exits from the maze of apoptosis?

PMID- 8863060
TI  - Chemospheric evaluation.

PMID- 8863061
TI  - Hidden persuasion.

PMID- 8863062
TI  - Allotropes versus polymorphisms.

PMID- 8863063
TI  - Attachment disruption in anorexia nervosa and bulimia nervosa: a review of theory
      and empirical research.
AB  - OBJECTIVE: To critically review both the theoretical propositions about the
      connections between attachment disruption and eating disorders and the empirical
      work directly examining these associations. METHOD: The major theoretical
      positions advocating an influential role for disruptions in the early development
      of secure attachments in the development of eating disorders were identified and
      a comprehensive review of empirical studies derived from these positions
      undertaken. RESULTS: There is evidence for the presence of attachment
      disturbances in eating-disordered populations and for an association of these
      disturbances with key aspects of eating disorder psychopathology. DISCUSSION:
      Because of the limitation of the single pathway conceptualization adopted by the
      theoreticians and researchers reviewed, few inferences about the role of
      attachment processes in the etiology and maintenance of eating disorders can be
      drawn from the existing literature. The paper argues for the development of
      multifactorial and process-orientated models of the role of attachment functions
      in the pathogenesis of eating disorders.

PMID- 8863064
TI  - The relationship between sexual abuse and eating pathology.
AB  - OBJECTIVE: The present study examined whether patients with histories of sexual
      abuse reported a higher degree of pathological eating behaviors and attitudes
      than a nonsexually abused control group. METHOD: Subjects, 134 psychiatric
      inpatients, completed the Eating Disorder Inventory (EDI) to assess eating
      pathology, and a questionnaire that gathered information regarding sexual abuse
      experiences. RESULTS: A logistic regression model found that a complex of EDI
      subscales was significantly related to a history of childhood abuse. Exploratory
      analyses found that survivors of sexual abuse obtained higher scores on the EDI
      subscales scores of Drive for Thinness, Interpersonal Distrust, Perfectionism,
      and Interoceptive Awareness. Further, the mean score for sexual abuse survivors
      without an eating disorder on the majority of EDI subscales was above established
      means for eating-disordered groups. DISCUSSION: These findings suggest that
      inpatients with a history of sexual abuse are likely to present with eating
      disorder symptomatology.

PMID- 8863065
TI  - The influence of sexual orientation on body dissatisfaction in adult men and
      women.
AB  - OBJECTIVE: Whereas gay culture's presumed emphasis on physical appearance may
      potentiate body dissatisfaction, lesbian culture's seeming lack of emphasis on
      appearance may protect against body dissatisfaction. We examined body
      dissatisfaction, associated psychosocial variables, and affiliation with the gay
      and lesbian community. METHOD: Self-report measures were administered to 257
      subjects (69 lesbians, 72 heterosexual women, 58 gay men, and 58 heterosexual
      men). RESULTS: Compared with heterosexual men, gay men reported significantly
      more body dissatisfaction and more distress in many of the psychosocial areas
      related to body dissatisfaction. In contrast, lesbians and heterosexual women did
      not differ in these areas. Although affiliation with the gay community was
      associated with body dissatisfaction in gay men, affiliation with the lesbian
      community was unrelated to body dissatisfaction in lesbians. DISCUSSION: It seems
      that aspects of the gay community increase vulnerability to body dissatisfaction,
      yet the values of the lesbian community do not seem to be protective against body
      dissatisfaction.

PMID- 8863066
TI  - Coping, sexual abuse, and compensatory behavior.
AB  - OBJECTIVE: We explored rates of sexual abuse in different diagnostic subgroups of
      eating disorder patients, and the extent to which sexually abused patients
      presented with a higher incidence of disturbed behavior, affective distress, and
      personality disturbance. Further, we explored Waller's hypothesis that self
      criticism may be an important mediator between sexual abuse, compensatory
      behavior, and personality disturbance. METHOD: We assessed sexual abuse in 103
      eating disorder patients, and compared abused and nonabused patients on measures
      of coping, eating disorder symptoms, affective distress, personality disorders,
      and behavioral dysregulation. RESULTS: Although the overall rate of abuse was
      equivalent to previous reports, about 40%, frequency of abuse was strikingly
      different across diagnostic subgroups, ranging from 12% to 75%. Abuse was lowest
      in compulsive overeaters (12%) and highest in patients who engaged in
      compensatory behaviors but did not binge or meet criteria for anorexia (75%).
      Abused patients were not only more disturbed on comorbid psychiatric symptoms,
      but were more likely to have engaged in self-injurious behavior (80%) and
      attempted suicide (75%). Consistent with Waller's model, self-criticism was the
      only primary coping strategy to differentiate abused from nonabused patients.
      DISCUSSION: The findings indicate the possible need for a reprioritization of
      purging and compensatory behaviors in the diagnostic schedule for eating
      disorders, and the importance of assessing sexual abuse as a comorbid factor.

PMID- 8863067
TI  - Prospective study of outcome in bulimics as a function of Axis-II comorbidity:
      long-term responses on eating and psychiatric symptoms.
AB  - We assessed prognostic implications of categorical personality disorder (PD)
      diagnoses at selected points during and following treatment for bulimic
      syndromes. Seventy-six bulimic cases were organized into Borderline PD, Other PD,
      or No PD groups, and then assessed at pretreatment, after 3 months of therapy,
      and at termination (after a modal 8 months). Results at 3- and 12-month
      posttreatment follow-ups (available in 43 and 38 cases, respectively) provided a
      reflection of status after therapy termination. On comorbid symptoms, borderline/
      nonborderline differences were very striking: Borderlines showed more initial
      psychiatric symptoms than did nonborderlines, and despite improvements, retained
      disturbances of clinical magnitude to completion of therapy and into follow-up.
      On eating symptoms, borderline/ nonborderline differences were less dramatic, the
      overall pattern implying that borderlines showed only marginally poorer response
      in selected areas of disturbance. Results corroborate others linking Axis-II
      comorbidity to unfavorable outcome in the eating disorders, but suggest that
      character disturbance is more strongly linked to course of general psychiatric
      symptoms than it is to course of eating disturbances. We discuss clinical
      implications of differing strengths of association observed between eating and
      psychiatric symptoms, on the one hand, and Axis-II pathology, on the other.

PMID- 8863068
TI  - Substance use among women with eating disorders.
AB  - OBJECTIVE: The results of past research suggest that bulimics are more likely
      than anorexics to engage in substance use, and that binge eating and/or purging
      may be an indicator of increased likelihood of substance use. We further
      investigated substance use among women with eating disorders. METHOD: We compared
      women with anorexia nervosa (n = 134) to women with bulimia nervosa (n = 320)
      with regard to history of substance use and investigated potential relationships
      between eating disorder symptom presentation and substance use. RESULTS: Even
      after controlling for age and eating disorder symptom severity, women with
      bulimia nervosa were more likely than those with anorexia nervosa to have used
      alcohol, amphetamines, barbituates, marijuana, tranquilizers, and cocaine.
      Independent of diagnostic category, severity of caloric restriction was
      predictive of amphetamine use, severity of binge eating was predictive of
      tranquilizer use, and severity of purging was predictive of alcohol, cocaine, and
      cigarette use. DISCUSSION: Results are discussed in relation to the results of
      past research and with an emphasis on the importance of considering eating
      disorder symptom presentation in addition to formal eating disorder diagnosis.

PMID- 8863069
TI  - Bulimic psychopathology and attentional biases to ego threats among non-eating
      disordered women.
AB  - OBJECTIVE: It has been proposed that bulimic psychopathology is associated with
      responsiveness to ego threats, rather than to physical threat. However, the
      concept of ego threat is a heterogeneous one, and needs to be more clearly
      defined. This study examined the relationship between bulimic attitudes and
      attentional biases to different forms of threat. METHOD: The participants were 80
      non-eating-disordered women, drawn from school and University populations. Each
      woman completed a Stroop task, measuring attentional biases toward five different
      forms of threat. Their times to complete these tasks were associated with scores
      on the Eating Disorders Inventory. RESULTS: Bulimic (but not restrictive)
      attitudes were specifically associated with an attentional bias toward ego
      threats that are self-directed, rather than with ego threats that are perceived
      to come from others. DISCUSSION: It is suggested that there is a complex
      relationship between attention to self-directed ego threats, poor self-esteem
      (ineffectiveness), and bulimic psychopathology, although the causal structure of
      the relationship remains to be established. The results require replication with
      an eating-disordered sample.

PMID- 8863070
TI  - Disordered eating and its psychosocial correlates among Chinese adolescent
      females in Hong Kong.
AB  - OBJECTIVES: To study the prevalence of disordered eating and its relationship
      with body dissatisfaction, family dysfunction, and depression among Chinese
      adolescent females in Hong Kong. METHOD: Two hundred ninety-four schoolgirls
      completed a demographic and weight history sheet, Eating Attitudes Test-26, Body
      Dissatisfaction Scale, cohesion and conflict subscales of the Family Environment
      Scale, and the Beck Depression Inventory. RESULTS: 6.5% of subjects were EAT-26
      high scores. Disordered eating was positively predicted by body dissatisfaction
      and, to a lesser extent, family cohesion and conflict. Body dissatisfaction was
      in turn positively predicted by depression, which was negatively predicted by
      family cohesion. DISCUSSION: Western patterns of body dissatisfaction and
      disordered eating attitudes are common among Chinese adolescent females. In the
      presence of psychosocial vulnerability factors, more weight control behavior and
      eating disorders may be expected to arise in Hong Kong.

PMID- 8863071
TI  - Prevalence of eating disorders among Norwegian women and men in a psychiatric
      outpatient unit.
AB  - OBJECTIVE: The primary purpose of the study was to establish lifetime and point
      prevalence of different eating disorders in a psychiatric outpatient population
      of both men and women. METHOD: A questionnaire was sent out to 364 patients
      referred to a psychiatric outpatient department. Of these questionnaires, 234
      (64.3%) were completed and returned. Patient questionnaires were analyzed to
      assess the prevalence for different groups of eating disorders according to DSM
      III-R criteria. RESULTS: In women there was a lifetime prevalence of 5.2% of
      anorexia nervosa (AN), 16.1% bulimia nervosa (BN), 6.5% binge eating disorder
      (BED), and 11.0% eating disorder not otherwise specified (EDNOS), in total 38.7%.
      The point prevalence was 1.9% AN, 5.2% BN, 3.2% BED, nd 8.4% EDNOS, in total
      18.7%. The lifetime prevalence in men was 0% AN, 10.7% BN, 6.7% BED, and 4.0%
      EDNOS, in total 21.3%. Point prevalence was found to be 0% AN, 2.7% BN, 5.3% BED,
      and 6.7% EDNOS, in total 14.7%. Staff information yielded substantially lower
      rates of eating disorders among these patients. There was a significantly higher
      rate of eating disorders in the close family of eating-disordered patients
      compared to the patient group without such a disorder. DISCUSSION: The results
      support earlier studies indicating that younger patients have more eating
      disorders. The men showed frequencies of BN and BED at the same level as women,
      but the frequency of EDNOS was lower, and there were no cases of AN.

PMID- 8863072
TI  - Psychiatric symptoms in clients presenting for commercial weight reduction
      treatment.
AB  - OBJECTIVE: To study the prevalence and severity of psychiatric symptoms in a
      group of clients presenting to a commercial weight reduction program, compared
      with a group of patients seeking outpatient medical treatment. METHOD: Sixty-six
      clients presenting for commercial weight loss treatment and 52 patients
      presenting for general outpatient medical treatment were given self-report
      measures of anxiety (Spielberger State and Trait Inventory), depression (Beck
      Depression Inventory), body dissatisfaction (Body Shape Questionnaire), and
      overall impairment in functioning (Sheehan Disability Scale). RESULTS: Weight
      loss clients had significantly higher rates of depressive symptomatology and
      psychosocial disability than patients presenting for medical treatment. Weight
      loss clients were also more likely to demonstrate body dissatisfaction regardless
      of actual weight. Levels of anxiety were not significantly different, despite the
      medical group reporting themselves to be in poorer health as compared with the
      weight loss group. DISCUSSION: Regular screening for psychiatric symptoms in
      clients presenting for commercial weight reduction treatment may be valuable as
      this group may constitute an as yet unidentified cohort requiring psychiatric
      intervention.

PMID- 8863073
TI  - Role of television in adolescent women's body dissatisfaction and drive for
      thinness.
AB  - OBJECTIVE: Many authors have implicated the media's promotion of an
      unrealistically thin ideal for women as a major causal factor in the current high
      levels of body dissatisfaction and increasing incidence of eating disorders. The
      present study aimed to investigate the relationship between exposure to one
      medium, television, and body dissatisfaction and drive for thinness. METHOD:
      Questionnaires were administered to 94 adolescent women who reported how much and
      what television they had watched in the previous week. Body dissatisfaction and
      drive for thinness were also assessed. RESULTS: Amount of television watched did
      not correlate with either body dissatisfaction or drive for thinness, but
      category of program did. Specifically, amount of time spent watching soaps,
      movies, and (negatively) sport predicted body dissatisfaction, and the watching
      of music videos predicted drive for thinness. DISCUSSION: The results are
      consistent with sociocultural explanations for body dissatisfaction and for the
      emergence of eating disorders in young women.

PMID- 8863074
TI  - Why is attendance variable at groups for women with bulimia nervosa? The role of
      eating psychopathology and other characteristics.
AB  - OBJECTIVE: A substantial number of bulimic patients either fail to complete group
      therapy or miss a large number of sessions. This study examines the differences
      in eating psychopathology and other clinical features of women who either drop
      out of group therapy or attend intermittently. METHOD: Fifteen women who attended
      group therapy for bulimia completed measures of their eating psychopathology and
      other characteristics at the outset of the group. The women who completed the
      group were compared with those who did not, and the proportion of sessions
      attended was correlated with the women's pretreatment characteristics. RESULTS:
      In general, poor attendance at group therapy for bulimic disorders appears to
      have been related to the group not addressing the women's immediate wishes (e.g.,
      weight loss). Good attendance was associated with more severe levels of bulimic
      pathology (binging and vomiting). DISCUSSION: These findings are related to the
      small existing literature. Clinicians setting up groups might use these
      conclusions to indicate who would be most likely to benefit from group therapy
      for bulimic disorders.

PMID- 8863075
TI  - Anorexia nervosa: refeeding and hypophosphatemia.
AB  - A case of anorexia nervosa (AN) is reported where heart failure occurred
      secondary to severe hypophosphatemia despite oral phosphate supplementation. We
      recommend starting patients with AN on oral phosphate when refeeding is begun,
      monitoring serum phosphate every 1 to 2 days for at least the first week of
      refeeding, and discontinuation of refeeding during phosphate supplementation
      should severe hypophosphatemia develop.

PMID- 8863076
TI  - A case of comorbid anorexia nervosa, bulimia nervosa, and Munchausen's syndrome.
AB  - Reports of comorbid eating disorders and Munchausen's syndrome are rare. As part
      of a follow-up study of the outcome of anorexia nervosa, medical records and
      direct structured psychiatric interview data were collected on all women treated
      for anorexia nervosa in Christchurch, New Zealand between 1981-1984. On
      interview, one participant received diagnoses of anorexia nervosa, bulimia
      nervosa, and factitious disorder (Munchausen's syndrome). The subject interwove
      symptoms of her eating disorders with factitious presentations on several
      occasions. This diagnosis had not been apparent prior to compilation of all
      medical records.

PMID- 8863077
TI  - Prisons or prevention? Which really costs more?

PMID- 8863078
TI  - Adolescents as witnesses to violence.
AB  - A questionnaire, adapted from Gladstein assessed the teen's personal witnessing
      of certain violent acts or personal knowledge of victims of violent acts. The
      population as a whole personally knew more victims of violence compared to having
      actually witnessed violent acts. More than one-third of the surveyed population
      responded positively to each question about knowing victims, except with regard
      to victims of rape. Our study was conducted in a general adolescent medicine
      clinic in a large Midwestern city, and our data were compared to those of a
      previous study done in Baltimore, Maryland. Both studies showed similar positive
      responses in 10 of the 18 items surveyed. Further study is needed to determine
      the potential impact of this widespread exposure to violence on psychosocial
      functioning.

PMID- 8863079
TI  - The relationship of partner support to outcomes for teenage mothers and their
      children: a review.
AB  - This article reviews the literature on the relationship of partner support to
      outcomes for teenage mothers and their children. It discusses the changing
      alliance over time between men who father their babies and the young mothers and
      their children. This report considers both adults and adolescents who father
      children with adolescent women. The discussion focuses on the relationship
      between partner support and three outcomes for the mothers: educational outcomes,
      economic outcomes, and psychological well-being. The general association between
      partner support and the children's development is also examined. In addition,
      partner support is viewed within the context of the teenager's family system,
      providing a framework for assessing key features of support for teenage mothers.
      The article outlines suggestions for future research.

PMID- 8863080
TI  - Concurrent risk factors for adolescent violence.
AB  - PURPOSE: To examine the risk and protective factors for different types of
      violent behavior in a sample of high school age adolescents drawn from the
      general population, illuminate the multiple and cumulative nature of the
      different risk factors, and characterize gender differences in explanatory
      variables that foster involvement in violent activities. METHODS: Using data from
      a 6-year longitudinal self-report survey of over 4,500 high school seniors and
      high school dropouts from California and Oregon, we developed weighted estimates
      of the proportions of youth exhibiting different risk factors who are also
      involved in violent activities. We use risk scales to show the cumulative effects
      of multiple factors within substantive domains, and logistic regression
      techniques to pinpoint the effects of each risk factor relative to others
      included in the models. RESULTS: Major risk factors for violence include gender
      and deviant behaviors, such as using and selling drugs, committing nonviolent
      felonies, and engaging in other forms of nonviolent delinquency. Low academic
      orientation, lack of parental affection and support, and perceptions of parents'
      substance use also show strong links with violent behavior. As the number of risk
      factors increases, so does the likelihood of engaging in violent behavior. Boys
      and girls show somewhat different paths to violence, with girls being
      comparatively more susceptible to the effects of family problems or disruption
      and impaired relationships with parents. For boys, engaging in other deviant
      behaviors provides the most information about their propensity to commit violent
      acts. Weak bonds with school and family also have an impact on serious violence
      for boys. CONCLUSIONS: Risk factors from multiple domains--demographic,
      environmental, and behavioral--contribute to involvement in various types of
      violent behavior. The strong links between violence, drug use, and delinquency
      argue for prevention/intervention programs that take into account the clustering
      of these behaviors, while the contribution of weak familial and school bonds
      point to the need for efforts to strengthen these institutions. Research is
      needed to identify effective ways of achieving these ends.

PMID- 8863081
TI  - Evaluation of comprehensive violence prevention education: effects on student
      behavior.
AB  - PURPOSE: This study evaluates the impact on student behavior of violence
      prevention education in school settings. METHODS: School records were obtained
      for three panels (1985, 1986, and 1987) of urban public high school students (n =
      1,523) who were nonrandomly assigned to three different conditions of school
      based violence prevention education: (1) in a class-specific comprehensive
      educational intervention, (2) as part of a school-wide violence prevention
      initiative, and (3) no exposure. Changes in suspension status from sophomore to
      junior year were tracked within exposure groups and the risk of junior year
      suspension was compared across exposure groups, controlling for age, gender,
      race, absenteeism, and previous year suspension. RESULTS: The class-specific
      exposure, compared to a not-exposed group from the same school showed a
      significant 71% reduction in suspension rates (RR = .286, CI .12, .66). The
      school-wide exposure school shows reductions in and maintenance of very low rates
      of junior year suspension in each cohort year, although these are not always
      statistically significantly different from not-exposed groups. CONCLUSION:
      Results indicate that violence prevention education can reduce negative school
      behaviors, particularly when other supportive curricula and activities are added.

PMID- 8863082
TI  - Comparison of two violence prevention curricula for middle school adolescents.
AB  - OBJECTIVE: To compare the effectiveness of the Violence Prevention Curriculum for
      Adolescents to the Conflict Resolution: A Curriculum for Youth Providers among
      middle school students. METHODS: A sample (N = 225) of adolescents (males = 48%)
      representing 20% of the student population in two middle schools were
      administered a pretest questionnaire. Of these students, 89% were African
      American, 10% were white, and 1% were Native-American and lived in public housing
      (40%) or in neighborhoods adjacent to public housing (60%). Each school was
      randomly assigned to one of the curricula. Each curriculum was administered
      during 10 50-min sessions held twice a week over 5 weeks. One week later, 209
      students who completed the 10 sessions were tested with the same questionnaire.
      The data were analyzed with a repeated-measures analysis of variance. RESULTS:
      Students who received either curriculum reported significant decreases in their
      self-reported use of violence in hypothetical conflict situations, frequency of
      use of violence in the previous 30 days, and frequency of physical fights in the
      previous 30 days. The conflict resolution curriculum was more effective in
      reducing the frequency of fights resulting in an injury requiring medical
      treatment in the previous 30 days. CONCLUSIONS: Both curricula were successful in
      reducing three indicators of violence. However, the conflict resolution approach
      was more successful in reducing the frequency of more severe physical fights
      requiring medical treatment. The latter finding is of particular importance,
      because that physical fighting is the form of violence behavior in which young
      adolescents most often engage.

PMID- 8863084
TI  - Sexual behavior of adolescents with chronic disease and disability.
AB  - PURPOSE: This study aimed to assess sexual behaviors, sexual orientation,
      pregnancy, and abuse history among adolescents with and without chronic
      conditions. METHODS: Analyses were based on a statewide survey of 36,284 young
      people in the 7th through 12th grades for analytic purposes; subsets were defined
      using a specialized cohort design including adolescents with visible and
      nonvisible conditions plus controls. Principle outcome measures included self
      report of ever having sexual intercourse, age of sexual debut, reasons for not
      having intercourse, ever causing or having a pregnancy, ever having a sexually
      transmitted disease (STD), contraceptive use and reasons for their nonuse,
      history of sexual abuse, and sexual orientation. RESULTS: No differences were
      evident between adolescents with and without chronic conditions in the proportion
      ever having intercourse, age of sexual debut, pregnancy involvement, patterns of
      contraceptive use, or sexual orientation. No differences were evident among girls
      or boys with visible compared with invisible conditions. A significantly greater
      proportion of girls and boys with invisible conditions than controls reported a
      history of sexual abuse. More index boys than controls reported ever having an
      STD, whereas more girls with visible conditions than controls reported this.
      CONCLUSIONS: Adolescents with chronic conditions are at least as sexually
      involved as their peers, and significantly more likely to have been sexually
      abused. Visibility of chronic conditions does not appear to affect the sexual
      behaviors of adolescents. The need for comprehensive sexuality education in this
      population is high, and discussion of sexuality, contraception and abuse must be
      part of standard psychosocial assessment and anticipatory guidance for all
      teenagers, including those with chronic conditions.

PMID- 8863083
TI  - Adolescents' reasons for and experience after discontinuation of the long-acting
      contraceptives Depo-Provera and Norplant.
AB  - PURPOSE: The objectives of this study were to examine the reasons for
      discontinuation of the long-acting contraceptives Depo-Provera and Norplant in
      adolescents, and to assess the adolescents' experience after discontinuation of
      the methods. METHODS: A total of 35 adolescents [gynecologic age 4.7 +/- 0.3
      years, and body mass index (BMI) 24.2 +/- 0.6] who discontinued Depo-Provera, and
      31 adolescents (gynecologic age 3.4 +/- 0.3 years, BMI 24.1 +/- 0.9) who
      discontinued Norplant were periodically assessed during use of the methods and up
      to 12 months after discontinuation. RESULTS: The most common reasons for
      discontinuation of both Norplant (after 21.8 +/- 1.6 months of use) and Depo
      Provera (9.2 + 0.9 months of use) were irregular menstrual bleeding (64%), weight
      gain (41%), and increased headaches (30%). Resumption of menstrual regularity and
      dysmenorrhea was noted sooner after discontinuation of Norplant, compared with
      Depo-Provera. The increase in BMI noted at discontinuation of Depo-Provera (1.1,
      P = .0005) and Norplant (1.3, P = .03) persisted up to 6 months after
      discontinuation of either method (0.6, P = .01 post-Depo-Provera discontinuation;
      and 0.9, P = 0.02 post-Norplant discontinuation). Only 62% of the adolescents
      reported no break in contraceptive practice. The condom was the most popular
      method (37%) after discontinuation of Depo-Provera, and oral contraceptive (39%)
      after discontinuation of Norplant. The cumulative conception proportion reached
      0.93 at 12 months after discontinuation of Norplant, and was significantly higher
      (P = .01) compared with the cumulative proportion of conception after
      discontinuation of Depo-Provera (P = .50). CONCLUSIONS: Health care providers
      should aggressively manage physical problems associated with Depo-Provera and
      Norplant use, and expedite the transition to a new contraceptive method to
      minimize the high pregnancy rate observed after discontinuation of these methods
      in adolescents.

PMID- 8863085
TI  - Impact of a social support program on teenage prenatal care use and pregnancy
      outcomes.
AB  - PURPOSE: This study evaluated the impact of a resource mothers program (RMP) on
      prenatal care use, low birth weight (LBW), and preterm birth (PTB). The
      intervention used paraprofessional women to provide social support to pregnant
      teenagers through home visiting. METHODS: Data were obtained by linking RMP,
      health department, and birth certificate data. Outcomes for primiparous teenagers
      were compared across two main study groups: a RMP group (n = 1,901) and a
      comparison group from counties in which the program was not offered (n = 4,613).
      Multiple logistic regression was used to estimate the effects of program
      participation with simultaneous adjustment for age, race, marital status, and
      previous pregnancies. Odds ratios (OR) and 95% confidence intervals (CI) were
      calculated. RESULTS: Resource mothers program teenagers were more likely to
      initiate prenatal care early (OR = 1.48; CI = 1.32-1.66) and to receive adequate
      prenatal care (OR = 1.58; CI = 1.40-1.78) than teenagers in the other counties.
      The program had no significant effect on LBW, but unmarried teenagers in the RMP
      group were less likely to have a PTB than unmarried teenagers in the other
      counties with an OR of 0.81 (CI = 0.70-0.95). These findings were supported by
      analyses using a second comparison group. CONCLUSIONS: Given that PTB contributes
      heavily to infant mortality, the program's effect on PTB is promising.

PMID- 8863086
TI  - Trichotillomania and anorexia nervosa in an adolescent female: a case study of
      comorbidity.

PMID- 8863087
TI  - Puberty questions asked by early adolescents: what do they want to know?
AB  - OBJECTIVE: We undertook the following study to document questions asked by early
      adolescents regarding pubertal development. METHODS: As part of a health
      education program, 159 sixth-grade students (mean = 12.1 years) were surveyed to
      obtain their questions about puberty and their self-assessed pubertal stage.
      Questions were coded for content and gender specificity. RESULTS: Of 159 initial
      subjects, 111 generated a total of 200 questions. A majority of the questions
      reflected biological topics (88%), such as genital physiology (26%) and sexuality
      and reproduction (26%). Only 6% addressed psychosocial questions. Both females
      and Asians (compared with other ethnic or racial groups) expressed greater
      interest in the differences between male and female development (P < .05).
      Prepubertal males were more concerned about general puberty than were boys in
      later Tanner stages (P < .05). Earlier maturing males focused on genital anatomy
      (P < .05). CONCLUSIONS: We found that biological questions concerning puberty
      predominated over psychosocial topics, and that the gender, race or ethnicity,
      and stage of development determined the kinds of questions that early adolescents
      have about pubertal development. Health educators and clinicians may need to
      focus on physiologic areas to provide more meaningful information about
      development to early adolescents.

PMID- 8863088
TI  - Chronic illness and emotional distress in adolescence.
AB  - OBJECTIVE: The purpose of this study was to investigate emotional distress and
      suicidal ideation among adolescents with and without chronic illness. METHODS:
      Two groups were compared from the Barcelona Adolescent Health Survey (3,129
      students aged 14-19 years) data base. The index group included 162 adolescents
      with chronic conditions (100 females and 62 males) including those with asthma,
      diabetes, seizures, or cancer. No differences in prevalence of emotional distress
      or suicidal ideation were found among the four categories of disease. The control
      group included 865 subjects (383 females and 482 males). No age differences were
      evident between the index and control groups. Chi-square and Student's t-test
      were used for intergroup comparisons, with the criterion value set at p < .01 to
      reduce the probability of type I error. Analyses were conducted separately by
      gender. RESULTS: Compared with controls, a significantly greater proportion of
      females with chronic illness reported emotional problems, feeling in a bad mood,
      feeling sad, believing nothing amused them, having suicidal thoughts, expressing
      depressive symptomatology, and having personal problems needing professional
      help. In contrast, no significant group differences were found for males. No
      gender differences were found regarding recent contact with a mental health
      specialist. CONCLUSIONS: Chronic illnesses were associated with substantive
      emotional distress and suicide ideation in females but not in males. Females with
      chronic conditions did not, however, seek mental health services more often than
      their non-chronically ill counterparts. This suggests serious shortcomings in
      identification of "at-risk" youth and effective outreach to this population.

PMID- 8863089
TI  - Adolescents with physical disabilities: some psychosocial aspects of health.
AB  - PURPOSE: To examine the psychosocial issues related to growing up with a physical
      disability. METHODS: Adolescents with physical disabilities aged 11-16 years were
      compared with a Canadian national sample of adolescents using the Health
      Behaviours in School-Aged Children (HBSC), a World Health Organization Cross
      National Study survey. RESULTS: Adolescents with physical disabilities reported
      good self-esteem, strong family relationships, and as many close friends as
      adolescents in the national sample. However, adolescents with physical
      disabilities participated in fewer social activities and had less intimate
      relationships with their friends. They had more positive attitudes toward school,
      teachers, and their fellow classmates than the national sample, but fewer had
      plans for postsecondary education. The majority of adolescents with physical
      disabilities reported that they had not received information on parenthood, birth
      control, and sexually transmitted diseases. CONCLUSIONS: There are a number of
      critical areas of risk for adolescents with physical disabilities to which health
      promotion efforts should be directed. These include lower levels of peer
      integration, heightened adult orientation, low educational aspirations, and poor
      knowledge of sexuality.

PMID- 8863090
TI  - Commentary on Siegel, Minshew, and Goldstein.

PMID- 8863091
TI  - Wechsler IQ profiles in diagnosis of high-functioning autism.
AB  - A Wechsler Intelligence Scale profile characterized by VIQ < PIQ with lowest
      subtest score on Comprehension and highest on Block Design has been associated
      with autism. Recently, this profile has been applied to assess the accuracy of
      diagnosis in research samples and for differentiating autism from similar
      disorders in high-functioning individuals. Universality of this profile, however,
      has not been sufficiently demonstrated. We therefore examined WISC-R and WAIS-R
      profile characteristics in 81 rigorously diagnosed high-functioning (VIQ and FSIQ
      > 70) children (n = 45) and adults (n = 36) with autism. Analysis of the profiles
      in these groups did not reveal the presumed typical VIQ < PIQ pattern. The
      typical subtest pattern was found, but the magnitude of profile variability was
      small. We concluded that individuals with autism can demonstrate a wide range of
      ability levels and patterns on the Wechsler scales, without a single
      characteristic prototype. Use of IQ score profiles in the diagnosis and
      differential diagnosis of autism in high-functioning individuals is not
      considered valid.

PMID- 8863092
TI  - Teaching preschool age autistic children to make spontaneous initiations to peers
      using priming.
AB  - Children with autism rarely initiate social interactions with their peers.
      Currently available interventions have not increased autistic children'
      spontaneous initiations in natural settings without extensive teacher
      involvement. A "priming" strategy consisting of a low demand, high reinforcement
      session prior to the regular school activity was used to increase the spontaneous
      social initiations of 2 preschool age autistic boys to typically developing peers
      in a regular preschool classroom. Peers were also trained to independently
      respond to initiations. Implications for developing practical ways to improve
      autistic children's social functioning in regular school settings are discussed.

PMID- 8863093
TI  - Visual-spatial orienting in autism.
AB  - Visual-spatial orienting in high-functioning adults with autism and both
      chronological- and mental-age normal controls was examined. Three experiments
      were conducted in which stimuli were presented centrally and/or laterally (left
      or right of central fixation), and either detection or identification was
      required. The group with autism differed from normal controls by responding
      faster to central than to lateral stimuli, and by showing a left visual field
      advantage for stimulus detection only in the simplest condition (lateral
      presentations alone). Discussion focuses on the apparent abnormalities in
      disengaging/shifting attention, and on the coordination of attentional and motor
      systems in autism.

PMID- 8863094
TI  - Dysregulated immune system in children with autism: beneficial effects of
      intravenous immune globulin on autistic characteristics.

PMID- 8863095
TI  - A case-control study of obstetric complications and later autistic disorder.
AB  - The precise etiology of autism remains unclear. Obstetric adversity has been
      described as one factor that may increase the risk for the disorder. We examined
      the contemporaneous birth records of 49 children satisfying DSM-III-R criteria
      for autistic disorder, at four Dublin maternity hospitals, using the previous
      same-sex live birth in that hospital as a control. Data were evaluated blind to
      subject status using two obstetric complication (OC) rating scales. No
      significant differences in obstetric adversity were found between index and
      control groups. Autistic individuals did not differ from controls in terms of
      previously described risk factors for this disorder (maternal age, maternal
      parity, birth order, and low birth weight) in autism. These data do not support
      the view that OCs increase the risk for later autism.

PMID- 8863097
TI  - Abdominal fat distribution and insulin levels only partially explain adverse
      cardiovascular risk profile in Asian Indians.
AB  - BACKGROUND: Asian Indians show an increased risk of non-insulin-dependent
      diabetes mellitus (NIDDM) and coronary heart disease, together with adverse fat
      distribution and hyperinsulinaemia relative to other ethnic groups. Using
      population-based data, we investigated the question of whether the adverse fat
      distribution observed in Indians can be explained by differences in behavioural
      risk factor levels. We have examined the question of whether ethnic differences
      in fat distribution are responsible for the unfavourable risk factor profile of
      Indians. SUBJECTS AND METHODS: Fat distribution (waist: hip ratio) was compared
      in population-based samples of Asian Indian (n = 4394), Creole (n = 1746), and
      Chinese (n = 425) Mauritians, after controlling for body mass index and other
      factors. The contribution of this ratio to ethnic differences in cardiovascular
      disease risk factors and the role of fasting insulin concentrations were also
      determined. RESULTS: Indian men had the highest mean waist: hip ratio, despite
      having the lowest body mass index. In Indian women the mean waist: hip ratio and
      body mass index were intermediate between those of Chinese and Creole women.
      Indians of both sexes had low levels of high-density lipoprotein (HDL)
      cholesterol and HDL: total cholesterol compared with Creoles or Chinese, whereas
      triglycerides levels were highest in Indian men but intermediate in Indian women.
      Mean fasting and 2 h insulin concentrations were not consistently highest in the
      Indian subgroups. Blood pressure and serum urate levels were lowest in Indians of
      both sexes and Indian women also had lower total cholesterol concentrations than
      either Creoles or Chinese. The elevated waist: hip ratio in Indians was not
      explained by differences in physical activity, cigarette smoking, or alcohol
      consumption and the differences in this ratio (and insulin levels) did not
      explain the observed ethnic differences in metabolic parameters. CONCLUSIONS: The
      susceptibility of Indians to abdominal obesity contributed to the less desirable
      levels of some, but not all, cardiovascular risk factors. Ethnic differences in
      cardiovascular risk factors in Mauritians were not explained by differences in
      abdominal obesity, serum insulin or behavioural risk factors. These data suggest
      that it is over-simplistic to ascribe the adverse cardiovascular risk factor
      profile commonly observed in Asian Indians to a tendency to abdominal obesity.

PMID- 8863096
TI  - Professional perceptions of children with developmental difficulties: the
      influence of race and socioeconomic status.

PMID- 8863098
TI  - Decline of coronary heart disease mortality in The Netherlands from 1978 to 1985:
      contribution of medical care and changes over time in presence of major
      cardiovascular risk factors.
AB  - OBJECTIVE: To study the relative contributions of medical care and changes in
      cardiovascular risk factors to the decline in coronary heart disease (CHD)
      mortality in The Netherlands from 1978 to 1985. METHODS: The number of potential
      CHD deaths prevented in this period was estimated by subtracting the number of
      observed CHD deaths from the number of deaths that would have occurred without
      any change in age-specific CHD mortality. In addition, the number of myocardial
      infarctions over this period was determined. Using estimates of risk associated
      with smoking, based on national and international data, of effects of changes in
      total cholesterol level, of benefits of antihypertensive drug treatment and
      effects of different intervention strategies in subjects with a previous
      myocardial infarction, we calculated the relative contribution of the separate
      factors to the decline in CHD mortality. RESULTS: The estimated contribution of
      treatment in coronary care units, postinfarction treatment and coronary bypass
      grafting to the fall in CHD mortality was 46%. Approximately 44% of the decline
      in CHD mortality could be attributed to primary prevention efforts (cessation of
      smoking, change in cholesterol level and treatment of hypertension). CONCLUSION:
      On the basis of available estimates of the potential effects of primary and
      secondary prevention it seems likely that a sizeable proportion of the age
      specific reduction in mortality in The Netherlands during the period 1978-85
      could have resulted from these measures. However, our findings should be
      considered to be estimates illustrating the relative benefits of different
      strategies rather than absolute figures.

PMID- 8863099
TI  - Serum lipoprotein(a) levels in a Greek population sample without a history of
      premature myocardial infarction.
AB  - OBJECTIVE: To investigate lipoprotein(a) levels in a Greek population sample.
      METHOD: Serum apolipoprotein [Apo(a)] concentrations were measured in 220 men and
      190 women aged 55-65 years without a history of effort angina or myocardial
      infarction. RESULTS: The distributions of Apo(a) and lipoprotein(a) [LP(a)]
      levels were highly skewed both in men and in women. The level of 30 mg/dl Lp(a)
      corresponded to the 77th percentile of the Lp(a) distribution in men but to the
      66th percentile in women. Women had significantly higher values of Apo(a) or
      Lp(a) concentration than men. High-density lipoprotein cholesterol levels tended
      to be higher in women, but not in men, belonging to the fourth and fifth
      quintiles of the Lp(a) distribution than in those belonging to the three lower
      quintiles.

PMID- 8863100
TI  - The concept of cardioreparation: Part 1. Pathophysiology of remodelling.
AB  - PURPOSE: Left ventricular hypertrophy is common in patients with hypertension or
      congestive heart failure and in survivors of myocardial infarction. It is
      associated with increased risks of adverse cardiovascular events, including
      angina, myocardial infarction and congestive heart failure. We aimed to explain
      these observations in terms of changes in the structure of the heart,
      collectively described as remodelling. DATA EXTRACTION: Laboratory investigations
      of animal models of cardiovascular diseases were reviewed. The most prominent
      features of remodelling are myocyte hypertrophy, excessive accumulation of
      collagen in the heart (myocardial fibrosis) and pathological changes in the
      coronary blood vessels. Remodelling disrupts the structure of the heart and
      impairs its pumping function and blood supply. The reversal of remodelling,
      termed cardioreparation, could restore cardiac structure and function towards
      normal and improve the prognosis of patients with cardiovascular diseases.
      CONCLUSIONS: Cardioreparation implies the regression of myocyte hypertrophy and
      myocardial fibrosis. Myocyte hypertrophy is primarily a response to chronic
      pressure or volume overload of the ventricles, whereas myocardial fibrosis
      depends on activation of circulating and tissue renin-angiotensin-aldosterone
      systems. Angiotensin converting enzyme inhibitors reduce blood pressure and
      inhibit these systems. They might therefore induce cardioreparation.

PMID- 8863101
TI  - The concept of cardioreparation: Part 2. Medical implications of
      cardioreparation.
AB  - PURPOSE: Left ventricular hypertrophy (LVH) caused by systemic hypertension,
      myocardial infarction and congestive heart failure is associated with
      pathological changes in the structure of the heart, collectively described as
      remodelling (see part 1 of this review). The reversal of remodelling, termed
      cardioreparation, might restore cardiac structure and function towards normal,
      thereby improving the prognosis of these conditions. We aimed to explore the
      medical implications of this concept. DATA EXTRACTION: Clinical trials of
      angiotensin converting enzyme (ACE) inhibitors and other drugs in patients with
      hypertension, myocardial infarction and congestive heart failure were reviewed.
      The results showed that ACE inhibitors induce regression of LVH in hypertensive
      patients, reduce mortality in acute myocardial infarction, and reduce morbidity
      and mortality in patients with congestive heart failure or left ventricular
      dysfunction subsequent to myocardial infarction. These observations are
      consistent with cardioreparation by ACE inhibitors. CONCLUSIONS: ACE inhibitors
      reduce morbidity and mortality in patients with myocardial infarction or
      congestive heart failure. Theoretical considerations and some clinical
      observations suggest that these benefits might result from cardioreparation.

PMID- 8863102
TI  - Smoking and socioeconomic status in a population-based inner city sample of
      African-Americans, Latinos and whites.
AB  - OBJECTIVE: To examine patterns of cigarette smoking among individuals of
      different socioeconomic status (SES) and ethnicity. DESIGN: A cross-sectional and
      longitudinal community-based random household sample. METHODS: Unmarried African
      American, Latino and while men and women, aged 20-44 years, living in San
      Francisco in 1988-9 and in 1989-90, were surveyed regarding prior and current
      smoking. Evaluation of behaviors was based on responses to an interviewer reading
      questions related to the variables of interest. SES was primarily based on
      educational attainment. RESULTS: Overall, 40% of respondents smoked, with an
      inverse association in univariate analysis between smoking and educational
      attainment in each gender/ethnic subgroup, except for Latino men. After
      controlling for other variables, ethnicity and education predicted smoking: with
      Latinos as referent, whites [odds ratio (OR) = 3.2] and African-Americans (OR =
      2.7) were more likely to stroke, and there was a consistent graded inverse
      association between educational attainment and smoking (P < 0.0001). Of smokers,
      after controlling for other variables, heavy smokers (> or = 1 pack/day compared
      with < 1 pack/day) were more likely to be older (P < 0.0001) and white (OR = 7.1)
      than African-American (OR = 1.8) or Latino (OR = 1.0), and there was trend toward
      heavy smokers being less educated (P = 0.06). One year later, 1422 (80%) of the
      original participants were resurveyed. Of 563 baseline smokers, 96 (17%) reported
      having quit, with African-Americans less likely to quit than whites or Latinos (P
      < 0.05). Of 859 baseline nonsmokers, 34 (4%) had started to smoke 1 year later.
      CONCLUSIONS: In a population-based inner city sample, the prevalence of smoking
      was considerable and there was a strong inverse association between smoking and
      educational attainment in almost all ethnic and gender subgroups. Further studies
      are needed to explore the possible reasons for these differences so that
      culturally sensitive risk factor interventions may be developed and tested.

PMID- 8863103
TI  - Using a coronary risk score for screening and intervention in general practice.
      British Family Heart Study.
AB  - AIM: To investigate whether a risk score proposed by the British Regional Heart
      Study (BRHS), derived from data collected in 1978-1980, provides an appropriate
      basis for current coronary risk factor screening and intervention in general
      practice. METHODS: The BRHS risk score was applied to 1993 men aged 40-59 years
      and 1353 women aged 35-59 years, from 13 general practices in England, Wales and
      Scotland, who had health checks during 1991-1992 in the British Family Heart
      Study (FHS). Modifications to the BRHS risk score were made in order to identify
      subjects with a current high risk compared with others of the same age and sex.
      These were validated on 3272 men and 2229 women recruited from different general
      practices during 1992-1994 in the FHS. RESULTS: Only 9% of men in the FHS fell
      into the published top (highest risk) quintile of the BRHS score, versus an
      expected 20%, and 44% fell into the bottom quintile. Scores were, on average,
      substantially lower in the FHS men than in the BRHS men, principally because of
      lower measured cholesterol levels (using a Reflotron) and a lower prevalence of
      cigarette-smoking. The BRHS scores also tended to increase with age,
      disproportionately identifying older subjects, and were substantially lower in
      women than in men. Simple age-related modifications to the risk score were
      therefore devised to overcome these problems. These modifications performed well
      in the validation. CONCLUSIONS: The substantial difference in risk scores between
      the BRHS and FHS men may reflect both a real reduction in risk and changes in
      calibration and methodology. Current use of the BRHS risk score may therefore
      mislead doctors and patients in the direction of complacency. In addition, the
      published BRHS risk score has an age-dependence that is undesirable in terms of
      guiding the intensity of lifestyle intervention which should be offered to an
      individual patient. The simple modifications proposed provide a more appropriate
      basis for coronary risk factor screening and intervention in general practice,
      and one that can be used both for men and for women.

PMID- 8863104
TI  - Inter-relationships of plasma fibrinogen, low-density lipoprotein cholesterol,
      cigarette smoking and the prevalence of cardiovascular disease.
AB  - BACKGROUND: The magnitude of the cardiovascular risk associated with plasma
      fibrinogen concentration is influenced separately by cigarette smoking and by low
      density lipoprotein (LDL) cholesterol levels. The effects of combinations of
      these factors on risk and the extent to which inclusion of the plasma fibrinogen
      level further refines the risks associated with smoking and high LDL cholesterol
      levels are not known. OBJECTIVE: To determine the inter-relationships among all
      of the three factors smoking, LDL cholesterol level and fibrinogen level with
      respect to the occurrence of cardiovascular disease. METHODS: The study was part
      of the Edinburgh Artery Study, which was a cross-sectional random sample survey
      of 1592 men and women aged 55-74 years. The assessment of cardiovascular disease
      included recall of diagnosis by a doctor of angina or myocardial infarction,
      intermittent claudication determined by a questionnaire and measurement of ankle
      systolic blood pressure. RESULTS: The odds ratio for disease in smokers in the
      top tertiles of plasma fibrinogen and LDL cholesterol levels was 7.7 (95%
      confidence interval 3.0-19.8; P < or = 0.001). Neither a multiplicative nor a
      synergistic effect of the three factors on the odds of disease was observed but
      the level of each contributed to the risk. For example, in current smokers in the
      bottom tertile of LDL cholesterol level, the odds of disease were 6.1 (95%
      confidence interval 2.2-17.0; P < or = 0.001) in the top tertile, 2.9 (95%
      confidence interval 1.0-8.6; P < or = 0.05) in the middle tertile and 1.6 (95%
      confidence interval 0.5-4.8; P > 0.05) in the bottom tertile of plasma fibrinogen
      level. Subjects in the bottom tertile of plasma fibrinogen level did not have
      significantly elevated (P < 0.05) risks irrespective of LDL cholesterol levels
      and smoking status. CONCLUSION: The incorporation of plasma fibrinogen level
      permitted more precise delineation of the odds of disease within categories of
      smoking and LDL cholesterol concentration. These relationships need to be
      investigated further in prospective studies.

PMID- 8863105
TI  - Evidence from a chronobiometric approach that chronic smokers, although
      normotensive, show an increase in diurnal blood pressure.
AB  - OBJECTIVE: To investigate the effects of chronic smoking on the 24 h blood
      pressure and heart rate pattern in normotensive subjects. METHODS: Twenty-five
      smokers and 25 age-, weight- and height-matched non-smokers, who were all
      clinically healthy young men, gave their informed consent to undergo non
      invasive, automated, ambulatory blood pressure monitoring for 24 h. The smokers
      in this study consumed on average 25.4 cigarettes per day. The lifestyle of the
      two groups was comparable because they worked as clerks at the same company. The
      24 h blood pressure and heart rate data were analysed according to
      chronobiological methods. RESULTS: Smokers were found to show a statistically
      significantly higher blood pressure versus non-smokers by day but not by night.
      Furthermore, smokers showed a slight increase in the mean level of circadian
      blood pressure rhythm versus non-smokers, accompanied by an amplification of one
      cyclic component of this periodicity. CONCLUSIONS: The increase in diumal blood
      pressure in smokers might be regarded as the haemodynamic effect of chronic
      smoking in normotensive subjects. Such an effect seems to be substantiated
      pathophysiologically by an amplitude overmodulation of one of the harmonic
      components which confer the circadian blood pressure rhythmicity. Because the
      diumal increase in blood pressure persists for two-thirds of the day-night
      period, one can argue that this phenomenon in normotensive smokers might be a
      premonitory sign of future hypertension. Apart from this, one can hypothesize
      that the diumal increase in blood pressure might itself be a cause of target
      organ damage, given its consistent within-day duration and daily repetition.

PMID- 8863106
TI  - Bibliography current world literature.

PMID- 8863107
TI  - Evaluation of a regional oxygen saturation catheter for monitoring SjvO2 in head
      injured patients.
AB  - OBJECTIVES: Monitoring jugular venous oxygen saturation (SjvO2) has been useful
      for the early identification and treatment of cerebral ischemia in patients with
      severe head injury. However, the catheters that have been used for this purpose
      have not performed optimally. The purpose of this study was to evaluate the
      performance of a new regional oxygen saturation catheter for monitoring SjvO2.
      METHODS: Eighteen regional oxygen saturation catheters, 4-Fr in diameter (Baxter
      Healthcare Corporation, Edward Critical Care), were used in this study. Each
      catheter was inserted percutaneously into the dominant jugular vein and the
      catheter's tip position in the jugular bulb was verified by radiograph. The
      catheter was calibrated in vitro prior to insertion using the optic calibrator
      provided by the manufacturer. The catheter was recalibrated every 8 to 12 hours
      by comparing the oxygen saturation value from the catheter with that measured by
      a co-oximeter in a blood sample drawn through the catheter. RESULTS: In vitro
      calibration using the optic calibrator was not always successful. Five catheters
      could not be calibrated. The remaining 13 catheters could all be calibrated, but
      only 9 provided a value that was within 4% of the oxygen saturation derived from
      the blood sample. After the first in vivo calibration, the correlation between
      the catheter and the blood sample values was improved. A total of 196 comparisons
      were made. The median, 25th, and 75th quartile differences between the catheter
      and the blood sample measurement of SjvO2 were 0.00, -1.15, and 1.25%,
      respectively. Using longitudinal data regression, the overall slope of the
      regression between the catheter and blood values was 0.997 (p = 0.001).
      CONCLUSIONS: The new regional oxygen saturation catheter provided reliable
      measurement of SjvO2 83% of the time when the signal quality index was < or = 3,
      and may be useful for continuous monitoring of SjvO2.

PMID- 8863108
TI  - Supraorbital artery as an alternative site for oscillometric blood pressure
      measurement.
AB  - OBJECTIVE: Noninvasive blood pressure measured from the superficial temporal
      artery has been shown to correlate well with pressure in the brachial artery. The
      supraorbital artery may be an even better site for monitoring blood pressure on
      the forehead because it originates from the internal carotid artery, and it is
      easier to locate anatomically. This study compares mean pressure measured
      oscillometrically over the supraorbital artery and at the upper arm. METHODS:
      Oscillometric signals from the supraorbital artery were recorded in 20 surgical
      patients under general anesthesia using a 2.5- x 1-cm bladder attached to the
      forehead with a self-adhesive pad. Blood pressure was measured simultaneously
      from the arm using a Dinamap 1846 blood pressure monitor, and the resulting data
      compared with the supraorbital artery measurements. RESULTS: The mean difference
      between 219 pairs of blood pressure measurements, from the forehead and the arm,
      was 3.8 mm Hg. The standard deviation of the differences was 7.4 mm Hg. The
      linear regression equation for the data was y = 0.98x + 3.25, with a standard
      error of estimate of 7.31 mm Hg. The correlation coefficient between the two
      measurements was 0.82. CONCLUSIONS: The results show that mean blood pressures
      measured oscillometrically from the supraorbital and brachial arteries agree and
      correlate well with each other. The supraorbital artery should be a good
      alternative site for blood pressure measurement.

PMID- 8863109
TI  - Comparison of four methods of automated recording of physiologic data at one
      minute intervals.
AB  - INTRODUCTION: This study aims to evaluate possible differences between the
      maximum, minimum, and mean value over each epoch, or the instantaneous value at
      the end of the interval, when recording physiological data at 1-minute intervals.
      METHODS: The mean arterial pressure (MAP), heart rate derived from the radial
      pulse (PULSE), end-tidal CO2 (etCO2), and the arterial O2 saturation by pulse
      oximeter (SpO2) were measured continuously in 10 patients during general
      anesthesia. Anesthesia was induced and maintained using the same technique for
      the first 10 minutes. At 1-minute intervals for each parameter, the maximum,
      minimum, and mean value (over the preceding minute), as well as the instantaneous
      value at the end of the recording epoch, were automatically downloaded to an
      electronic spreadsheet. The differences between the maximum and minimum, the
      maximum and mean, the mean and minimum, and the instantaneous and mean values
      were calculated for each patient. RESULTS: We found differences between the
      maximum and minimum values recorded over each interval, between the maximum and
      mean values, between the mean and minimum values, and between the mean and
      instantaneous values recorded at the end of each minute interval for all
      physiological parameters examined. CONCLUSIONS: From the data presented, we
      conclude that during the first 10 minutes of a general anesthetic, including
      anesthesia induction and endotracheal intubation, the values of physiologic
      parameters derived from different summary indices, namely the maximum, minimum,
      and mean values over the 1-minute interval or instantaneous at the end of the
      interval differ from each other. This source of error must be considered when
      designing systems for computerized recordkeeping of anesthesia charts and when
      interpreting the data stored in electronic databases.

PMID- 8863110
TI  - The anesthesia machine valve tester: a new device and method for evaluating the
      competence of unidirectional anesthetic valves.
AB  - OBJECTIVE: Current methods of determining anesthesia machine unidirectional valve
      (UDV) competence are time-consuming, ineffective, or carry the risk of
      transmitting infectious disease to the anesthetist or patient. New methods of
      testing these valves are needed. The purpose of this study was to determine the
      prevalence of incompetent UDVs at one institution by employing the Anesthesia
      Machine Valve Tester (AMVT), a new way to test anesthesia machine UDVs. METHODS:
      We tested each expiratory and inspiratory UDV on all anesthesia machines in
      functioning operating rooms at the Brigham and Women's Hospital. If a UDV was
      found to be incompetent, we cleaned and reseated it, and then tested it again
      with the AMVT. RESULTS: We found a 13% prevalence of UDV malfunction in our
      machines. Three of the 10 incompetent valves were repaired quickly by us and were
      made competent by either reseating the valve or by first cleaning and then
      reseating it. CONCLUSIONS: We found that the AMVT was able to detect UDV failure
      quickly with no risk to the tester or to the patient. We conclude that the AMVT
      can be used to check the UDV as recommended by the FDA anesthesia machine check
      out protocol.

PMID- 8863111
TI  - The use of the iSTAT portable analyzer in patients undergoing cardiopulmonary
      bypass.
AB  - OBJECTIVE: To evaluate the utility of the iSTAT blood analyzer, a bedside device
      for hematocrit, sodium, potassium, and glucose measurement during cardiopulmonary
      bypass (CPB). METHODS: Forty patients scheduled for elective CPB were evaluated
      prospectively. In addition to using the iSTAT analyzer, blood samples were
      analyzed at four time points: following induction of anesthetic, 10 min. after
      initiation of CPB, 60 min. after initiation of CPB, and following heparin
      neutralization by protamine. Blood glucose concentration was measured by the
      hospital laboratory using a Kodak Analyzer and by a glucose meter, electrolytes
      were evaluated by the Kodak Analyzer and BGE (a device which is commonly used for
      "satellite laboratory" determinations of electrolyte and blood gas results), and
      hematocrit samples were measured by the hospital laboratory using an NE 8,000 and
      a centrifuge. The means and standard deviations of the differences between the
      methods were calculated. RESULTS: The hematocrit values determined by the iSTAT
      machine, when adjusted for the level of total protein (according to
      manufacturer's directions), differed from the laboratory values by 0.53 +/- 1.46
      percentage points. An alternative to measuring total protein and making the
      adjustment is simply adding 1% to the hematocrit in the pre-CPB period and 3% on
      CPB or post-CPB, which we found to yield values that differed from the laboratory
      by 0.52 +/- 1.42 percentage points. For all four tests (hematocrit, sodium,
      potassium, and glucose) the iSTAT had a similar relationship to the laboratory
      values as did the other commonly used means (centrifuge, BGE, and glucose meter)
      of clinical evaluation. CONCLUSION: In summary, we found that in patients
      undergoing CPB, the iSTAT values agreed sufficiently well with standard
      laboratory values and that the iSTAT instrument can be relied upon for bedside
      measurements.

PMID- 8863112
TI  - Accuracy and precision of a new, portable, handheld blood gas analyzer, the IRMA.
AB  - OBJECTIVE: The accuracy and precision of the new IRMA (Immediate Response Mobile
      Analysis System, Diametrics, Inc., St. Paul, MN) handheld blood gas analyzer was
      compared with that of two benchtop blood gas analyzers. The IRMA consists of a
      notebook-sized machine and disposable cartridges, each containing a pH, a CO2 and
      an O2 electrode, and provides bedside (point-of-care) blood gas analysis.
      METHODS: A total of 172 samples (arterial and mixed venous) were obtained from 25
      informed, consenting patients undergoing cardiopulmonary bypass. The pH, PCO2 and
      PO2 of each sample was determined on four blood gas analyzers: NOVA Statlabs
      Profile 5 (NOVA Biomedical, Waltham, MA), the ABL-50 (Radiometer, West Lake, OH),
      and two IRMA machines. Linear regression and bias +/- precision were determined,
      comparing each of the analyzers with the NOVA. RESULTS: All three machines showed
      a similar, high degree of correlation with the NOVA for pH, PCO2, and PO2. The
      bias and precision of the IRMA machines compared with the NOVA was similar to
      that of the ABL compared with the NOVA for pH (NOVA:ABL -0.005 +/- 0.011;
      NOVA:IRMA 1 = 0.0026 +/- 0.025; NOVA:IRMA 2 = 0.0021 +/- 0.025), for PCO2
      (NOVA:ABL = -1.4 +/- 1.3 mmHg; NOVA: IRMA 1 = -1.3 +/- 1.9 mmHg; NOVA: IRMA 2 = 
      1.2 +/- 2.1 mmHg) and PO2 (NOVA:ABL = 3.6 +/- 21.1 mmHg; NOVA:IRMA 1 = 3.4 +/-
      19.9 mmHg; NOVA:IRMA 2 = 6.3 +/- 20.9 mmHg). The bias found for pH, PCO2, and PO2
      was not affected by extremes of temperature (range 25.5-40 degrees C) or
      hematocrit (range 11-44%) for any machine. CONCLUSIONS: The new technology
      incorporated in the IRMA blood gas analyzer provides results with an accuracy
      that is similar to that of benchtop analyzers, but with all of the advantages of
      point-of-care analysis.

PMID- 8863113
TI  - Detection of intravenous fluid extravasation using resistance measurements.
AB  - Resistance to fluid infusion can be derived from measurements of pressure at two
      or more flow rates. We measured resistance in 31 patients using a pressure
      monitoring infusion pump (Model 560, IVAC) by recording pressure at five flow
      rates (0, 50, 100, 200, and 300 mL/hr), and computing resistance as the slope of
      the pressure versus flow curve. Resistance was measured subcutaneously (Rtissue)
      and intravenously (Rvein) immediately after unsuccessful or successful IV
      catheter placement. In all patients, Rtissue was always greater than Rvein. The
      difference ranged from 23 resistance units (RU) to 4166 RU, with a mean
      difference of 1147 RU (p < 0.0001, Student's t-test). Unpaired analysis of the
      data was performed to assess the ability of resistance to indicate extravasation
      in the absence of prior Rvein measurement. The median value for Rvein was 62 RU
      (range -13.6 to 420 RU), and for Rtissue, 544 RU (range 65.7 to 4170 RU).
      Receiver operating characteristic (ROC) analysis revealed that a 200-RU threshold
      detected infiltration with 0.90 sensitivity and 0.91 specificity. We conclude
      that elevated resistance during fluid infusion is an important early and easily
      measurable finding in fluid extravasation.

PMID- 8863114
TI  - Resistance to fluid flow in veins.
AB  - We evaluated the resistance to fluid infusion in the veins of 118 adult patients
      after intravenous catheter insertion prior to elective surgery. Hydraulic
      resistance in veins was defined as the slope of the pressure-flow relationship
      obtained by measuring venous pressure at several fluid flow rates. A resistance
      unit (RU) was defined as 1 mmHg/L/hr. Resistance in veins ranged from -12.1 to
      732 RU, with 50th and 95th percentiles being 22 and 198 RU, respectively. Venous
      resistance was not significantly affected by site of catheter insertion, tissue
      characteristics at the insertion site, age, sex, patient anxiety, American
      Society of Anesthesiologists physical status, or catheter size. This report
      provides a distribution of resistance to fluid infusion in arm veins of adult
      patients.

PMID- 8863115
TI  - Electrosurgery-induced ventricular fibrillation during pacemaker replacement--a
      unique mechanism.
AB  - Arrhythmias and pacemaker malfunction are known to occur from the use of an
      electrosurgical device. The present case report describes a patient with sick
      sinus syndrome who experienced ventricular fibrillation while undergoing surgery.
      During replacement of his non-functioning cardiac pacemaker under general
      anesthesia, electrosurgery was used to ensure hemostasis. Electric current may
      have stimulated myocardial leads present in the surrounding tissue, leading to
      ventricular fibrillation. The patient was resuscitated from the episode without
      any residual sequelae. Microshock and possible mechanisms that can lead to
      ventricular arrhythmias in patients with pacemakers during electrosurgery are
      discussed.

PMID- 8863116
TI  - The pediatric electrocardiogram: recognition of ischemia.

PMID- 8863117
TI  - Stimulability: a useful clinical tool.
AB  - Although difficult to define, stimulability is an easily measured skill that can
      provide valuable information for clinicians treating children with phonological
      disorders. In this article, we review changing trends in the definition of
      stimulability, standardized and nonstandardized approaches to its measurement,
      and clinical implications of stimulability for prognosis and treatment plan
      development as they have evolved over a 40-year period. Clinical application of
      stimulability information in caseload management and intervention is emphasized.

PMID- 8863119
TI  - Assessing stimulability in toddlers.
AB  - This article describes the development and use of a novel, script-based
      stimulability task for toddlers. A detailed description of the task and
      procedures for administration is provided. The task assesses stimulability for
      fricatives, affricates, and liquids in isolation and single words through
      presentation of toys and objects in a script format during play. Three different
      levels of cueing are provided to elicit the desired sounds/words. Selected
      findings from examination of the performance of 10 toddlers with normal speech
      language development and 10 with delayed development at an initial assessment and
      a 6-month reassessment are also described. Results suggest that stimulability
      testing may be successful with toddlers through the use of a scripted task and
      that they are more responsive to direct elicitations. Both groups added
      stimulable sounds; however, there was considerable individual variation with
      respect to specific sounds added and the addition of nonstimulable sounds as
      well. Stimulability testing is clinically useful as a dynamic assessment tool for
      toddlers because it may reveal information regarding a child's speech that is not
      obtainable with other measures and is also beneficial for individualized
      intervention planning.

PMID- 8863118
TI  - Factors associated with speech-sound stimulability.
AB  - Speech-sound stimulability as a clinical procedure has been used in speech
      language pathology for more than 60 years although review of the archival
      literature on this clinical construct provides little information on what factors
      may be associated with it. In this study, the factors found to relate to
      stimulability were articulation visibility, the child's age, the family's
      socioeconomic status, and the child's overall imitative abilities. Perception,
      severity, otitis media history, language abilities, consistency of productions,
      amount of stimulations provided, and willingness to self-correct were not
      associated with stimulability. Potential explanations are provided on the basis
      of prior research.

PMID- 8863120
TI  - The role of stimulability in the assessment and treatment of Spanish-speaking
      children.
AB  - Stimulability has been used successfully in planning treatment of phonological
      disorders in English-speaking children. The effectiveness of stimulability on the
      treatment of phonological disorders in speakers of languages other than English
      has not been investigated. Specifically, its role in treatment planning of
      phonological disorders in Spanish-speaking children has yet to be explored. The
      purpose of this article is to discuss the role of stimulability in the assessment
      and treatment of phonological disorders in Spanish-speaking children. Further, a
      case study applying these principles to a Spanish-speaking child with a
      phonological disorder is presented.

PMID- 8863121
TI  - Stimulability considerations in the phonological treatment of a child with a
      persistent disorder of speech-sound production.
AB  - The term "persistent sound system disorder" has been used to describe the speech
      problems of a relatively small group of children that does not respond readily to
      treatment. This group includes children who have been given diagnoses such as
      development apraxia of speech. In this article, a rationale is developed for one
      approach to the treatment of persistent sound system disorder. This approach,
      which involves broadening of the phonetic inventory early in the treatment
      process, is contrasted with more traditional motor-programming treatments that
      emphasize stabilization of a restricted set of inconsistently produced sounds.
      The treatment procedures advocated in this article are illustrated in a case
      study. The article concludes with a discussion of evolving theories and
      technologies that are likely to impact upon the assessment and treatment of
      children with persistent sound system disorders in the future.

PMID- 8863122
TI  - Enhancing stimulability: a treatment program.
AB  - Recent research on stimulability and generalization suggests that treatment of
      nonstimulable sounds results in maximum treatment gains (Powell, Elbert, &
      Dinnsen, 1991). It has also been suggested, however, that nonstimulable sounds
      are more difficult to teach, especially to young children with very small
      phonetic inventories. In this article, we describe a treatment program designed
      to increase the size of the phonetic inventory by "teaching" stimulability.
      Application of the treatment approach is demonstrated in a case study.

PMID- 8863123
TI  - Growth cone calcium elevation by GABA.
AB  - Cytoplasmic calcium plays a key role in neurite growth. In contrast to previous
      work suggesting that gamma aminobutyrate's (GABA) role in regulating growth cone
      calcium is primarily to antagonize the effects of glutamate, we report that GABA
      can act in an excitatory manner on developing hypothalamic neurites,
      independently raising calcium in growing neurites and their growth cones. Time
      lapse digital video and confocal laser microscopy with the calcium-sensitive dyes
      fluo-3 and fura-2 were used to study the influence of GABA on neurite calcium
      levels. GABA (10 microM) evoked a calcium rise in both bicarbonate- and Hepes
      based buffers. The calcium rise was greatly reduced after chloride transport was
      blocked. GABA raised calcium by stimulating the cell body, resulting in an
      increase in calcium throughout the neuronal cell body and dendritic arbor. GABA
      also acted locally, stimulating a neuritic calcium rise only in a single dendrite
      or growth cone. In some neurites and growth cones during early development, GABA
      generated a greater calcium rise than did glutamate. Bicuculline, a GABAA
      receptor antagonist, reduced calcium levels in neurites of young synaptically
      coupled neurons, indicating that ongoing synaptic release of GABA raised neuritic
      calcium. These data suggest that during early development, GABA may play a
      significant role in regulating process growth and modulating the formation of
      early connections in the hypothalamus. Our data support the hypothesis that GABA
      receptors are functionally active and may play a calcium regulating role similar
      to that of glutamate in neuronal development. This is particularly true in early
      development, as later in development GABA's role becomes more inhibitory, and
      glutamate plays the primary excitatory role.

PMID- 8863124
TI  - Synapses from medial olivocochlear branches in the inferior vestibular nucleus.
AB  - Olivocochlear neurons are auditory efferent neurons that convey information from
      the brainstem to the auditory periphery. With light and electron microscopy,
      using mice, we studied the central branches of medial olivocochlear neurons that
      are given off to the inferior vestibular nucleus. At the level of the electron
      microscope, the branches form synapses. The synapses are asymmetric with round
      vesicles, suggesting that they are excitatory. The synapses are formed mainly
      onto neuronal dendrites. These dendrites have a large range of diameters, and
      they may emanate from several types of target neurons. These results indicate
      that the inferior vestibular nucleus is an integrating center for vestibular,
      auditory, and other types of information, but the results do not fit with current
      theories about the function of the olivocochlear system.

PMID- 8863125
TI  - c-neu oncoprotein in developing rostral cerebral cortex: relationship to
      epidermal growth factor receptor.
AB  - The c-neu oncoprotein, p185c-neu, is a transmembrane tyrosine kinase that shares
      structural similarities with the receptor for epidermal growth factor (EGFr). We
      used immunoblots, immunoprecipitation, and immunohistochemistry 1) to test the
      hypothesis that p185c-neu and EGFr are coordinately expressed in central nervous
      system tissue and 2) to assess the spatiotemporal expression of both the c-neu
      oncoprotein and EGFr in the rostral cerebral cortex. In nondenaturing gels, anti
      c-neu antibody identified high molecular weight proteins (about 300-400 kDa) that
      were reduced by EDTA to a molecular weight of 180-200 kDa. Sodium dodecylsulfate
      polyacrylamide gel electrophoresis broke down this protein into an array of
      smaller peptides, which were expressed prenatally, transiently during the first
      three postnatal weeks, or in the adult. Perinatally, c-neu immunoreactivity was
      evident in subplate neurons, ascending processes of neurons in the cortical
      plate, and ventricular zone cells. During the second postnatal week, cells
      throughout cortex expressed somatodendritic immunostaining, but, in the adult, c
      neu immunoreactivity was expressed only by pyramidal neurons in layer V and by
      glia in the white matter and ependyma. EGFr-positive proteins behaved in the
      nondenaturing gels as did c-neu-positive oncoproteins, suggesting that both
      proteins naturally formed dimers. This contention was supported by the EGFr-or c
      neu immunolabeling of tissue that was previously immunoprecipitated with anti-c
      neu or anti-EGFr, respectively. The pattern of EGFr immunolabeling in the
      developing and mature cortex was virtually identical to that described for c-neu
      immunoreactivity. Cortical neurons express the c-neu oncoprotein and EGFr,
      probably as heterodimers. The specific immunolabeling of layer V neurons in the
      adult cortex with anti-c-neu and anti-EGFr suggests that the p185c-neu ligand and
      EGF regulate the activity of corticofugal systems. The expression of different c
      neu- and EGFr-positive peptides is developmentally defined and may be related to
      specific ontogenetic events.

PMID- 8863126
TI  - Development of cholinergic and GABAergic neurons in the rat medial septum:
      different onset of choline acetyltransferase and glutamate decarboxylase mRNA
      expression.
AB  - In the present study, we have investigated the developmental expression of the
      transmitter-synthesizing enzymes choline acetyltransferase (ChAT) and glutamate
      decarboxylase (GAD) in rat medial septal neurons by using in situ hybridization
      histochemistry. In addition, we have employed immunostaining for ChAT and the
      calcium-binding protein parvalbumin, known to be contained in septohippocampal
      GABAergic neurons. A large number of GAD67 mRNA-expressing neurons were already
      observed in the septal complex on embryonic day (E) 17, the earliest time point
      studied. During later developmental stages, there was mainly an increase in the
      intensity of labeling. Neurons expressing ChAT mRNA were first recognized at E
      20, and their number slowly increased during postnatal development of the septal
      region. The adult pattern of ChAT mRNA-expressing neurons was observed around
      postnatal day (P) 16. By using a monoclonal ChAT antibody, the first
      immunoreactive cells were not seen before P 8. Similarly, the first weakly
      parvalbumin-immunoreactive neurons were seen in the septal complex by the end of
      the 1st postnatal week. These results indicate that in situ hybridization
      histochemistry may be an adequate method to monitor the different development of
      transmitter biosynthesis in cholinergic and GABAergic septal neurons. Moreover,
      the late onset of ChAT mRNA expression would be compatible with a role of target
      derived factors for the differentiation of the cholinergic phenotype.

PMID- 8863127
TI  - Distribution of a reeler gene-related antigen in the developing cerebellum: an
      immunohistochemical study with an allogeneic antibody CR-50 on normal and reeler
      mice.
AB  - We have immunohistochemically investigated the expression of a reeler gene
      related antigen in the mouse cerebellum by using a monoclonal antibody, CR-50.
      This antibody probes a distinct allelic antigen present in normal but not in
      reeler mutant mice, and this antigen is localized in the brain regions in which
      morphological abnormalities occur in reeler mice (Ogawa et al., Neuron 14: 899
      912, 1995). The developing normal cerebellum showed transient immunoreactivity to
      CR-50 in a limited set of neurons and in the extracellular space near the pial
      surface. An early population of CR-50-labeled cells emerged on embryonic day (E)
      13 along the dorsal cerebellar surface, comprising the nuclear transitory zone
      (NTZ). Bromodeoxyuridine labeling revealed the time of origin of these cells to
      be at E11-12. From E14 to E18, some CR-50-labeled cells were stacked in the inner
      border of the external granular layer (EGL), whereas others were scattered in
      deep areas, such as the cerebellar nuclei and the surrounding intermediate zone
      or white matter. In the first postnatal week, these subcortical structures became
      immunonegative. However, CR-50 antigen was continuously produced until the second
      postnatal week by another population of cells occupying i) the premigratory zone
      (PMZ), the inner half of the EGL, and ii) the internal granular layer (IGL).
      These later CR-50-positive cells were smaller than the earlier type and showed
      the morphology typical of granule neurons. Both types of CR-50-labeled cells were
      positive for a DNA-binding protein, zic. By treating living cerebellar slices
      with CR-50, the extracellular antigen was localized as a puncutate staining
      pattern in the NTZ, PMZ, and molecular layer (ML), but not in the subcortical
      regions and IGL. Purkinje cells were negative for CR-50 and aligned as a
      monolayer adjacent to the PMZ, though their dendritic trees were closely
      associated with the extracellular CR-50-antigen in the PMZ and ML. Staining of
      dissociated cells suggested that the extracellular antigen is initially present
      throughout the surfaces of the CR-50/anti-zic double positive neurons, and is
      then rearranged to concentrate on their processes contacting with Purkinje cells.
      The spatiotemporal expressions of the CR-50 antigen in the cerebellum are
      consistent with the possibility that this antigen is involved in cell-cell
      interactions related to the histogenetic assembly of Purkinje cells.

PMID- 8863128
TI  - Synaptic and nonsynaptic monoaminergic neuron systems in the lamprey spinal cord.
AB  - In the lamprey spinal cord, dopamine- (DA) and 5-hydroxytryptamine-(5-HT)
      containing cells appear to play an important role in controlling the firing
      properties of motoneurons and interneurons and, thereby, in modulating the
      efferent motor pattern. To determine the detailed morphology and synaptic
      connectivity of the intraspinal DA and 5-HT systems in Lampetra fluviatilis and
      Ichthyomyzon unicuspis, DA and 5-HT antisera were used in light and electron
      microscopic immunocytochemical experiments. Two main groups of labeled cells were
      distinguished: DA-containing liquor-contacting (LC) cells distributed along the
      central canal, and 5-HT+DA-containing multipolar cells located near the midline
      ventral to the central canal. Both types were synaptically connected with other
      neuronal elements. The DA-immunoreactive LC cells, which extended a ciliated
      process into the central canal, received symmetrical synapses from unlabeled
      terminals containing small synaptic vesicles. The distal process of the LC cells
      could be traced to the lateral cell column, to the ventral aspect of the dorsal
      column, or to the ventromedial area. Ultrastructural analysis of DA fibers in
      these regions showed the presence of labeled terminals containing numerous small
      synaptic vesicles and a few dense-core vesicles. These terminals formed
      symmetrical synapses with unlabeled cell bodies and dendrites, with GABA
      immunopositive LC cells, and with the multipolar DA+5-HT cells. The multipolar
      DA+5-HT cells also received input from unlabeled synapses. Intracellular
      recording from these cells showed that they received excitatory postsynaptic
      potentials in response to stimulation of fibers in the ventromedial tracts and
      dorsal roots. The terminals of the multipolar DA+5-HT neurons in the ventromedial
      spinal cord contained numerous dense-core vesicles and small synaptic vesicles,
      but no synaptic specializations could be detected. In addition, a small number of
      larger DA-immunoreactive cells were observed in the lateral cell column at
      rostral levels. The lamprey spinal cord thus contains distinct populations of
      synaptically interconnected monoaminergic neurons. Dopamine-containing LC cells
      synapse onto DA+5-HT-containing multipolar cells, in addition to GABAergic LC
      cells and unidentified spinal neurons. In contrast, the multipolar cells appear
      to exert their influence by nonsynaptic mechanisms.

PMID- 8863129
TI  - Anatomy of the ventral nucleus of the lateral lemniscus in rats: a nucleus with a
      concentric laminar organization.
AB  - The lateral lemniscus contains relay nuclei of the auditory pathway in which the
      neurons have been grouped into dorsal and ventral (VNLL) nuclei. The data about
      the cytoarchitecture of the VNLL are controversial and no agreement exists
      concerning its tonotopical organization. In this paper, the cytoarchitecture of
      VNLL and the spatial distribution of its neurons projecting to the central
      nucleus of the inferior colliculus (CNIC) have been studied by using different
      tracers. Rats were iontophoretically injected in the CNIC and grouped in three
      sets. Group 1 rats received large injections of biotinylated dextran amine (BDA).
      Group 2 animals received restricted single injections of BDA in the low-, medium
      , or high-frequency regions of the CNIC. Group 3 rats were double injected, with
      horseradish peroxidase placed in the high-frequency region of the CNIC, and with
      biocytin in the low-frequency one. The distribution of retrogradely labeled
      neurons in the ipsilateral VNLL was three-dimensionally reconstructed by use of a
      computer microscope. The analysis of labeled neurons and Nissl material suggests
      that the VNLL contains flat stellate neurons. Labeled flat stellate neurons and
      fibers are oriented in parallel and form fibrodendritic laminae. The projection
      from the VNLL to the CNIC is topographically organized: neurons in peripheral
      laminae project to dorsolateral, low-frequency regions of the CNIC, and those of
      central laminae project to ventromedial, high-frequency regions. Each VNLL lamina
      forms a continuous ventrodorsal structure which resembles a helicoid.

PMID- 8863130
TI  - Visuotopic organisation of striate cortex in the marmoset monkey (Callithrix
      jacchus).
AB  - The visuotopic organisation of the primary visual cortex (V1) was studied by
      extracellular recordings in adult male marmosets (Callithrix jacchus) that were
      anaesthetised with sufentanil/nitrous oxide and paralysed with pancuronium
      bromide. Extensive sampling of the occipital region in four individuals and
      partial coverage of V1 in five others allowed not only the establishment of the
      normal visuotopy but also the study of interindividual variability. As in other
      primates, there was a single, continuous map of the contralateral hemifield in
      V1, with the upper visual quadrant represented ventrally and the lower quadrant
      represented dorsally. The surface area of V1, which was measured in two
      dimensional reconstructions of the cortical surface, varied from 192 to 217 mm2.
      There was a marked emphasis on the representation of the foveal and parafoveal
      visual fields: the representation of the central 5 degrees of the visual field
      occupied 36-39% of the surface area of V1, whereas the central 10 degrees
      occupied 57-59%. No asymmetry between the representations of the upper and lower
      quadrants was apparent. The visual topography of V1 was highly consistent between
      individuals, relative to both sulcal landmarks and stereotaxic coordinates. The
      entire contralateral hemifield was represented in V1; in addition, neurones with
      receptive fields whose borders invaded the ipsilateral hemifield were observed
      within V1, less than 800 microns from the V1/V2 boundary. The total invasion of
      the ipsilateral hemifield was less than 0.5 degree at the centre of the fovea but
      reached 8 degrees at the periphery of the vertical meridian. Our results
      demonstrate that the organisation of V1 is similar in diurnal New and Old World
      simians, despite major variations in size, ecological niche, and timing of
      postnatal development across species.

PMID- 8863131
TI  - Neuronal localization of the cyclophilin A protein in the adult rat brain.
AB  - Cyclophilin A is a small, soluble protein which binds the immunosuppressive drug
      cyclosporin A. Cyclophilin A is a peptidyl-prolyl isomerase and is widely
      expressed in a multitude of tissues, but is present in highest concentration in
      the brain. A role for this protein in the maturation and folding of neuron
      specific membrane proteins has been hypothesized. Immunohistochemical staining
      for cyclophilin A was used to determine whether cyclophilin A is present in
      neurons, and whether there is variation in the level of expression with respect
      to brain regions and cell types. The specificity of the antibody used was
      demonstrated by Western blot analysis and cyclosporin affinity purification.
      Immunohistochemical staining of sections of adult rat brain showed labelled
      neurons throughout the neuraxis. The intensity of the immunostaining observed was
      roughly equivalent to neuronal cell density and was restricted to gray matter. On
      a cellular level, staining was present in cytosol and nuclei and extended into
      neuronal processes. Fluorescent double-labelling experiments on hippocampal cell
      cultures revealed that all cells labelled with the cyclophilin A antibody also
      showed staining for the neuron-specific marker for microtubule-associated protein
      (MAP)2, and could, therefore, be identified as neurons. Immunoreactivity in these
      neurons is present in punctate, spinelike structures along dendrites. Cyclophilin
      A immunoreactivity was undetectable in glial fibrillary acidic protein (GFAP)
      positive cells. The pattern of cyclophilin. A expression is consistent with a
      role of cyclophilin A in neuronal protein maturation and folding in vivo.

PMID- 8863132
TI  - Neuroanatomical distribution of androgen and estrogen receptor-immunoreactive
      cells in the brain of the male roughskin newt.
AB  - Immunohistochemistry was used to investigate the neuroanatomical distribution of
      androgen and estrogen receptors in brains of adult male roughskin newts, Taricha
      granulosa, collected during the breeding season. Immunoreactive cells were found
      to be widely distributed in specific brain areas of this urodele amphibian.
      Androgen receptor-immunoreactive (AR-ir) cells were observed in the olfactory
      bulbs, habenula, pineal body, preoptic area, hypothalamus, interpeduncular
      nucleus, area acusticolateralis, cerebellum, and motor nuclei of the medulla
      oblongata. Estrogen receptor-immunoreactive (ER-ir) cells were found in the
      lateral septum, amygdala pars lateralis, pallium, preoptic area, hypothalamus,
      and dorsal mesencephalic tegmentum. This immunocytochemical study of the newt
      brain reveals AR-ir and ER-ir cells in several regions that have not been
      previously reported to contain androgen and estrogen receptors in non-mammalian
      vertebrates. Additionally, the distribution of AR-ir and ER-ir cells in the newt
      brain, in general, is consistent with previous studies, suggesting that the
      distribution of sex steroid receptor-containing neurons in some brain regions is
      relatively conserved among vertebrates.

PMID- 8863133
TI  - Sources of GABAergic input to the inferior colliculus of the rat.
AB  - We have studied the GABAergic projections to the inferior colliculus (IC) of the
      rat by combining the retrograde transport of horseradish peroxidase (HRP) and
      immunohistochemistry for gamma-amino butyric acid (GABA). Medium-sized (0.06-0.14
      microliter) HRP injections were made in the ventral part of the central nucleus
      (CNIC), in the dorsal part of the CNIC, in the dorsal cortex (DCIC), and in the
      external cortex (ECIC) of the IC. Single HRP-labeled and double (HRP-GABA)
      labeled neurons were systematically counted in all brainstem auditory nuclei. Our
      results revealed that the IC receives GABAergic afferent connections from ipsi-
      and contralateral brainstem auditory nuclei. Most of the contralateral GABAergic
      input originates in the IC and the dorsal nucleus of the lateral lemniscus
      (DNLL). The dorsal region of the IC (DCIC and dorsal part of the CNIC) receives
      connections mostly from its homonimous contralateral region, and the ventral
      region from the contralateral DNLL. The commissural GABAergic projections
      originate in a morphologically heterogeneous neuronal population that includes
      small to medium-sized round and fusiform neurons as well as large and giant
      neurons. Quantitatively, the ipsilateral ventral nucleus of the lateral lemniscus
      is the most important source of GABAergic input to the CNIC. In the superior
      olivary complex, a smaller number of neurons, which lie mainly in the periolivary
      nuclei, display double labeling. In the contralateral cochlear nuclei, only a few
      of the retrogradely labeled neurons were GABA immunoreactive. These findings give
      us more information about the role of GABA in the auditory system, indicating
      that inhibitory inputs from different ipsi- and contralateral, mono- and binaural
      auditory brainstem centers converge in the IC.

PMID- 8863134
TI  - An integrated pharmacokinetic and pharmacodynamic approach to controlled drug
      delivery.

PMID- 8863135
TI  - Modulation of blood-brain barrier permeability.
AB  - Genetic and other defects leading to brain changes in Down syndrome, Alzheimer
      disease, amyotrophic lateral sclerosis, Huntington disease, Gaucher disease,
      hypertension and other disorders are rapidly being identified. If brain access
      were possible, new candidates for gene replacement therapy, antisense
      oligonucleotides, immune proteins or growth factors might be used for treating
      these disease (Lowenstein et al., 1994; Wielbo et al., 1995). Further, a number
      of drugs, peptides, antibodies and biological response modifiers have proven
      valuable in inhibiting malignant, infectious and other pathological processes in
      vitro, but are unlikely to be employed clinically because of their limited access
      to brain.

PMID- 8863136
TI  - Nasal delivery. The use of animal models to predict performance in man.

PMID- 8863137
TI  - Evaluation of the efficiency of targeting of antitumor drugs: simulation analysis
      based on pharmacokinetic/pharmacodynamic considerations.
AB  - Antitumor drugs can be classified into two groups; cell cycle phase nonspecific
      (type I) and specific (type II) drugs. The cytotoxic activity of type I drugs
      depends on the time-concentration product (AUC), whereas that of type II drugs is
      time-dependent. Therefore, not only the AUC in the target organ, but also the
      exposure time is an important factor for evaluating the efficiency of any
      delivery system for antitumor drugs. In the present study, we examined the
      factors governing the cytotoxicity of drugs in tumors based on a hybrid perfusion
      model. It is suggested that the increase in tumor tissue binding of drug results
      in an increased unbound drug mean residence time (MRTT,U), leading to the
      increased activity of type II drugs. In contrast, the cytotoxic activity of type
      I drugs is unaffected by the alteration in the tissue binding since the
      intracellular AUC defined for unbound drugs (AUCT,U) is unaffected by the extent
      of drug binding. We also found that the symmetrical increase in the permeability
      surface area products (PS) for drug influx (PSinf) and efflux (PSeff) across the
      tumor plasma membrane results in the unaltered and reduced antitumor activity for
      the type I and type II drugs, respectively, due to the unaltered AUCT,U and to
      the reduced MRTT,U. The kinetic analysis suggests that the increase in
      PSinf/PSeff ratio results in the increased cytotoxic activity of both type I and
      type II drugs. Collectively, optimization of the antitumor activity can be
      attained by increasing the tissue binding for type II drugs and by increasing
      PSinf and/or by decreasing PSeff type I and type II drugs. The present simulation
      study was carried out by considering the pharmacodynamic features of antitumor
      drugs and was a method of predicting how the antitumor activity may change on
      altering each process (tissue binding and membrane permeability for the influx
      and efflux processes) which governs the characteristics of drug distribution to
      tumors.

PMID- 8863138
TI  - Nasal delivery of vaccines.
AB  - Only relatively recently the significance of inducing not only systemic immunity
      but also significant local immunity at susceptible mucosal surfaces has become
      appreciated. A new field of mucosal immunity has been established as information
      accumulates on mucosal-associated lymphoid tissue (MALT) and on its role in both
      local and systemic immune responses. This review describes the formation of
      vaccines to be delivered to one of MALT components, i.e. the nasal-associated
      lymphoid tissue (NALT), which bears some similarities with the Peyer's patches of
      the intestine. The association of antigens with adjuvants and particulate
      carriers such as microparticles, nanoparticles and liposomes is emphasised.

PMID- 8863139
TI  - High yield incorporation of plasmid DNA within liposomes: effect on DNA integrity
      and transfection efficiency.
AB  - Effective use of liposomes in gene therapy requires high yield incorporation of
      nucleic acids within vesicles which protect their content from nuclease attack
      and facilitate transfection: To that end, pGL2 plasmid DNA (3.99 x 10(6) Daltons)
      expressing the luciferase reporter gene was incorporated quantitatively (40-92%
      of the DNA used) by a mild procedure into neutral and negatively or positively
      charged multilamellar liposomes which offered considerable protection from
      deoxyribonuclease attack. Smaller vesicles (210-383 nm diameter) produced from
      such liposomes, retained much of the original content of DNA which was still
      significantly inaccessible to the enzyme. Liposomal plasmid DNA was found to
      retain its structural integrity and to transfect cells in vitro in relation to
      the size and surface charge of the vesicles. Such DNA-incorporating liposome
      constructs could prove effective for plasmid DNA expression in vivo.

PMID- 8863140
TI  - Preparation and evaluation of a time-controlled release capsule made of
      ethylcellulose for colon delivery of drugs.

PMID- 8863141
TI  - QALYs, lotteries and veils: the story so far.

PMID- 8863142
TI  - The ethics of complementary medicine.

PMID- 8863143
TI  - Should a doctor prescribe hormone replacement therapy which has been manufactured
      from mare's urine?
AB  - Many clinicians are experiencing consumer resistance to the prescription of
      equine HRT (that is hormone replacement therapy which has been manufactured from
      mare's urine). In this paper I consider the ethical implications of prescribing
      these preparations. I decide that patients should have a right to refuse such
      treatment but also ask whether a prescribing doctor should choose one preparation
      over another on moral grounds. I determine that there is prima facie evidence to
      suggest that mares may suffer and that prescription of equine HRT (instead of
      synthetic oestrogen-oestriol) would therefore have to be justified in terms of
      either offering greater benefits to the women or offering greater value for money
      to the health service. I find that there is no substantial evidence to suggest
      that equine HRT offers unique advantages over and above oestriol. I conclude that
      it would be preferable for a doctor to recommend the synthetic oestrogen to women
      who want relief from the symptoms of the menopause and protection from
      osteoporosis and cardiovascular disease.

PMID- 8863144
TI  - Double jeopardy, the equal value of lives and the veil of ignorance: a rejoinder
      to Harris.
AB  - Harris levels two main criticisms against our original defence of QALYs (Quality
      Adjusted Life Years). First, he rejects the assumption implicit in the QALY
      approach that not all lives are of equal value. Second, he rejects our appeal to
      Rawls's veil of ignorance test in support of the QALY method. In the present
      article we defend QALYs against Harris's criticisms. We argue that some of the
      conclusions Harris draws from our view that resources should be allocated on the
      basis of potential improvements in quality of life and quantity of life are
      erroneous, and that others lack the moral implications Harris claims for them. On
      the other hand, we defend our claim that a rational egoist, behind a veil of
      ignorance, could consistently choose to allocate life-saving resources in
      accordance with the QALY method, despite Harris's claim that a rational egoist
      would allocate randomly if there is no better than a 50% chance of being the
      recipient.

PMID- 8863145
TI  - Would Aristotle have played Russian roulette?
AB  - This paper continues the debate between myself and Peter Singer et al started in
      the Journal of Medical Ethics volume 21, no 3 about the ethical respectability of
      the use of QALYs in health care allocation. It discusses the question of what, in
      the way of health care provision, would be chosen by rational egoists behind a
      Rawlsian "veil of ignorance", and takes forward the vexed question of what is to
      count as "doing good" and hence as "doing the most good" in health care. Most
      importantly, this paper argues that it would be unfair to discriminate against
      people because they have been disadvantaged by their genetic condition. It notes
      that McKie et al in their reply to my first contribution to this debate continue
      to fail to distinguish between chance and probability and it is argued that this
      failure causes them to miss the whole point of the argument.

PMID- 8863146
TI  - Another peep behind the veil.
AB  - Harris argues that if QALYs are used only 50% of the population will be eligible
      for survival, whereas if random methods of allocation are used 100% will be
      eligible. We argue that this involves an equivocation in the use of "eligible",
      and provides no support for the random method. There is no advantage in having a
      100% chance of being "eligible" for survival behind a veil of ignorance if you
      still only have a 50% chance of survival once the veil is lifted. A 100% chance
      of a 50% chance is still only a 50% chance. We also argue that Harris provides no
      plausible way of dealing with the criticism that his random method of allocation
      may result in the squandering of resources.

PMID- 8863147
TI  - Potential and the early human.
AB  - Some form of potential or "capacity" is often seen as evidence of human moral
      status. Opinions differ as to whether the potential of the embryo should be
      regarded as such evidence. In this paper, I discuss some common arguments against
      regarding the embryo's potential as a sign of human status, together with some
      less common arguments in favour of regarding the embryo's potential in this way.

PMID- 8863148
TI  - Offering patients entry in clinical trials: preliminary study of the views of
      prospective participants.
AB  - OBJECTIVE: To ascertain attitudes to different methods of obtaining informed
      consent for randomised clinical trials (RCTs). DESIGN: Structured interviews with
      members of the public, medical secretaries and medical students. SETTING: The
      public were approached in a variety of public places. Medical secretaries and
      students were approached in their place of work. SUBJECTS: Fifty members of the
      public, 25 secretaries and 25 students. MAIN OUTCOME MEASURES: Views on RCTs were
      elicited, with particular emphasis on how subjects thought the concept of
      randomisation should be explained. Each participant was presented with
      descriptions of proposed clinical trials and asked to select his or her
      preference from a range of options. RESULTS: Written information was preferred
      over verbal information in 91% of replies. Most respondents (86%) would prefer to
      sign a consent form. Of the seven statements explaining randomisation, a
      significant difference was found in favour of explanations that were less
      explicit about the play of chance (ANOVA; p = 0.0004). Eighty-three per cent of
      participants thought that randomised trials were morally acceptable when there
      was no prior medical preference between treatments. However, over half (55%)
      thought they would find it upsetting to be offered entry in such a trial and a
      quarter thought the outcome of treatment might be adversely affected.
      CONCLUSIONS: Our results offer some support for the idea that "economy with
      truth" is less unsettling than a frank description of the stark reality of what
      randomisation means. It is a matter of debate as to whether, if we are correct,
      autonomy should have precedence over beneficence. The offer of entry in a
      clinical trial is likely to affect the experience of care for many people,
      especially if the process of randomisation is described explicitly. Potential
      participants should be given a detailed written explanation of the rationale for
      the trial and be asked to sign a consent form if they agree to take part.

PMID- 8863149
TI  - Consent to clinical research--adequately voluntary or substantially influenced?
AB  - In clinical research the giving of consent by the patient often lies within the
      context of illness or the doctor/patient relationship. On exploration of these
      issues it would appear unlikely that the patient's consent is free of substantial
      influences, some of which may be strong enough to be controlling. Five categories
      of consent are suggested: voluntary, involuntary, coerced, enforced and partially
      voluntary. It is argued that consent in clinical research is substantially
      influenced and thus only partially voluntary. Several practical strategies are
      proposed to ensure adequately voluntary consent by reducing some circumstantial
      influences when consent to clinical research is obtained.

PMID- 8863150
TI  - Random paired scenarios--a method for investigating attitudes to prioritisation
      in medicine.
AB  - OBJECTIVE: This article describes a method for investigating attitudes towards
      prioritisation in medicine. SETTING: University of Kuopio, Finland. DESIGN: The
      method consisted of a set of 24 paired scenarios, which were imaginary patient
      cases, each containing three different ethical indicators randomly selected from
      a list of indicators (for example, child, rich patient, severe disease etc.). The
      scenarios were grouped into 12 random pairs and the procedure was repeated four
      times, resulting in 12 scenario pairs arranged randomly in five different sets.
      SURVEY: This method was tested with four groups of subjects (n = 8, n = 47, n =
      104 and n = 36). RESULTS: Children and patients with a severe disease were
      prioritised in all groups. The aged, patients with a mild disease and patients
      with a self-acquired disease were negatively prioritised in all groups. Poor or
      rich patients were prioritised in some groups but negatively prioritised in
      others. CONCLUSIONS: The validity and reliability of this method are good and it
      is suitable for investigating attitudes towards medical prioritisation.

PMID- 8863151
TI  - Should intellectual property be disseminated by "forwarding" rejected letters
      without permission?
AB  - Substantive scientific letter writing is a cost-effective mode of complementing
      observational and experimental research. The value of such philosophically
      uncommitted and unsponsored well-balanced scientific activity has been relegated.
      Critical letter writing entails the abilities to: maintain rational scepticism;
      refuse to conform in order to explain data; persist in keeping common sense
      centre-stage; exercise logic to evaluate the biological significance of
      mathematical figures, including statistics, and the ability to sustain the will
      to share insights regarding disease mechanisms on an ostensibly lower research
      platform. During peer review, innovative letter writing may share the
      occasionally unfortunate fate of innovative research. Rejected scientific letters
      do not automatically lose copyright. Periodicals with high letter loads will see
      some valuable contributions wasted, but that is the price for maintaining
      autonomy in scientific publication. The scientific community is an integrated
      whole that must respect the rights of authors at all levels. Unauthorised
      forwarding of rejected letters sets the dangerous precedent of justifying unjust
      means.

PMID- 8863152
TI  - German family study on hereditary breast-ovarian cancer.
AB  - An estimated 5% to 10% of all breast and ovarian cancers are attributed to
      dominant susceptibility genes. Two such genes, BRCA1 and BRCA2, were recently
      identified. The involvement of these genes was studied in 43 German breast only
      and breast-ovarian cancer families. All families contained three or more cases of
      breast or ovarian cancer, with at least two diagnosed under the age of 60 years.
      Multipoint linkage analysis gave a maximum lod score of 2.13 at the BRCA1 locus
      under the assumption of genetic heterogeneity, with an estimated 50% of families
      being linked. Among the 33 breast only cancer and 10 breast-ovarian cancer
      families, the estimated proportions of linked families were 35% and 75%,
      respectively. Sixteen families with at least four cases of female breast cancer
      diagnosed under the age of 60 years, or male breast cancer diagnosed at any age,
      were analysed for linkage to BRCA2. Positive lod scores at BRCA2 were obtained in
      six families.

PMID- 8863154
TI  - Distribution of oculocutaneous albinism in Zimbabwe.
AB  - A survey of 1.3 million schoolchildren in Zimbabwe identified a total of 278
      pupils with oculocutaneous albinism (OCA), giving a prevalence of 1 in 4728.
      Pupils with OCA were identified in every province of the country, but the
      distribution was not even. In certain areas, notably the capital, Harare, and the
      eastern province of Manicaland, the frequency was significantly higher than in
      others. Although most of the pupils with albinism belonged to the majority Shona
      ethnic group, people with OCA were also found among the minority population
      groups in the country. There were almost twice as many pupils with albinism in
      rural compared with urban schools (248 v 129). However, the prevalence of OCA was
      significantly higher in urban than rural areas. These results indicate that data
      for a country collected solely in urban locations are likely to be biased and
      emphasise the need for widespread distribution of health and special educational
      facilities for affected people.

PMID- 8863153
TI  - Complex genetic predisposition to cancer in an extended HNPCC family with an
      ancestral hMLH1 mutation.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is characterised by a genetic
      predisposition to develop colorectal cancer at an early age and, to a lesser
      degree, cancer of the endometrium, ovaries, urinary tract, and organs of the
      gastrointestinal tract other than the colon. In the majority of families the
      disease is linked to mutations in one of the two mismatch repair genes, hMSH2 or
      hMLH1. We have found a novel hMLH1 nonsense mutation in a Swiss family with Lynch
      syndrome, which has been transmitted through at least nine generations. A
      different tumour spectrum of neoplasms of the skin, soft palate, breast,
      duodenum, and pancreas was observed in three branches of this family, where there
      was a virtual absence of colonic tumours. The hMLH1 mutation could not be
      detected in members of these branches suggesting that at least a second genetic
      defect predisposing to cancer is segregating in part of the kindred.

PMID- 8863155
TI  - Phenotypic variability in male patients carrying the mutant ornithine
      transcarbamylase (OTC) allele, Arg40His, ranging from a child with an
      unfavourable prognosis to an asymptomatic older adult.
AB  - In five different Japanese families, we identified six male hemizygotes (aged 6,
      9, 15, 17, 56, and 65 years) and a putative candidate (aged 48 years), carrying a
      mutant allele of the ornithine transcarbamylase (OTC) gene, a G to A substitution
      at nucleotide 119 in exon 2 generating histidine in place of arginine. OTC
      activity in the necropsied liver tissue was reduced to approximately 12% of the
      control and that of COS 1 cells transfected with Arg40His OTC cDNA was 10.2 +/-
      1.8% of the control transfected with wild type OTC cDNA. Clinical features ranged
      from death during a hyperammonaemic attack (a 9 year old) to a 65 year old
      asymptomatic man. We consider that the amount of protein ingested by these
      subjects may be one predisposing factor leading to the manifestation of this
      disease.

PMID- 8863156
TI  - The deletion of six amino acids at the C-terminus of the alpha 1 (II) chain
      causes overmodification of type II and type XI collagen: further evidence for the
      association between small deletions in COL2A1 and Kniest dysplasia.
AB  - We have identified an 18 bp deletion in exon 49 of the type II procollagen gene
      (COL2A1) in a patient with Kniest dysplasia. The deletion is located at the very
      C-terminus of the helical domain and removes two of three Gly-Pro-Pro triplets at
      positions 1007-1012, which are thought to be involved in helix formation and
      stability. Morphological investigation of an iliac crest biopsy showed large
      inclusions in the endoplasmic reticulum of chondrocytes, reflecting impaired
      secretion of type II collagen. Electrophoretic analysis of collagens extracted
      from cartilage or synthesised by cultured chondrocytes showed that type II and
      also type XI procollagen molecules containing mutant alpha 1 (II) chains showed
      post-translational overmodification. These observations provide further evidence
      for the general association of Kniest dysplasia with small deletions in the
      helical domain of type II collagen.

PMID- 8863157
TI  - PAX genes and human neural tube defects: an amino acid substitution in PAX1 in a
      patient with spina bifida.
AB  - From studies in the mouse and from the clinical and molecular analysis of
      patients with type 1 Waardenburg syndrome, particular members of the PAX gene
      family are suspected factors in the aetiology of human neural tube defects (NTD).
      To investigate the role of PAX1, PAX3, PAX7, and PAX9, allelic association
      studies were performed in 79 sporadic and 38 familial NTD patients from the Dutch
      population. Sequence variation was studied by SSC analysis of the paired domain
      regions of the PAX1, PAX7, and PAX9 genes and of the complete PAX3 gene. In one
      patient with spina bifida, a mutation in the PAX1 gene was detected changing the
      conserved amino acid Gln to His at position 42 in the paired domain of the
      protein. The mutation was inherited through the maternal line from the unaffected
      grandmother and was not detected in 300 controls. In the PAX3 gene, variation was
      detected at several sites including a Thr/Lys amino acid substitution in exon 6.
      All alleles were present among patients and controls in about the same
      frequencies. However, an increased frequency of the rare allele of a silent
      polymorphism in exon 2 was found in NTD patients, but no significant association
      was observed (p = 0.06). No sequence variation was observed in the paired domain
      of the PAX7 and PAX9 genes. Our findings so far do not support a major role of
      the PAX genes examined in the aetiology of NTD. However, the detection of a
      mutation in PAX1 suggests that, in principle, this gene can act as a risk factor
      for human NTD.

PMID- 8863158
TI  - No founder effect in three novel Alzheimer's disease families with APP 717 Val-
      >Ile mutation. Clerget-darpoux. French Alzheimer's Disease Study Group.
AB  - We sequenced exons 16 and 17 of the APP (amyloid precursor protein) gene in 18
      unrelated French Alzheimer's disease (AD) patients. These patients had an onset
      before the age of 60 and belonged to families with autosomal dominant
      transmission of the disease. We detected the APP 717 Val-->Ile mutation in three
      out of 18 (16.6%) families. In these three families, all affected subjects had
      the APOE 3/3 genotype, but their ages of onset ranged from 38 to 60 years,
      indicating that factors other than the APOE genotype influence age of onset.
      Analysis of two polymorphic loci adjacent to the APP gene showed that at least
      two independent mutational events had occurred within these pedigrees, in spite
      of their origin in the same region of France.

PMID- 8863159
TI  - Characterisation of four novel fibrillin-1 (FBN1) mutations in Marfan syndrome.
AB  - Forty-four percent of the fibrillin-1 gene (FBN1) from 19 unrelated families with
      Marfan syndrome was screened for putative mutations by single strand
      conformational polymorphism (SSCP) analysis. Four novel mutations were identified
      and characterised in five people, three with classical Marfan syndrome (two from
      one family, and one from an unrelated family), one with a more severe phenotype,
      and one with neonatal Marfan syndrome. The base substitutions G2113A, G2132A,
      T3163G, and G3458A result in amino acid substitutions A705T, C711Y, C1055G, and
      C1152Y, respectively. C711Y, C1055G, and C1152Y lead to replacement of a cysteine
      by another amino acid; the latter two occur within epidermal growth factor-like
      motifs in exon 25 and 27, respectively. The A705T mutation occurs at exon 16
      adjacent to the GT splice site. The A705T and C711Y mutations, at exon 16 and 17,
      respectively, are the first documented in the second transforming growth factor
      beta 1 binding protein-like motif of FBN1.

PMID- 8863160
TI  - Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35.
AB  - The macrophage resistance gene NRAMP1 regulates priming/activation of macrophages
      for enhanced TNF alpha, IL 1 beta, and MHC class II expression. Since all of
      these functions are of potential importance in the induction or maintenance or
      both of autoimmune disease, samples from the Arthritis and Rheumatism Council's
      repository of multicase rheumatoid arthritis families were typed for a
      dinucleotide repeat in the NRAMP1 promoter region and four other 2q34 (TNP1) or
      2q35 (IL8R, VIL1, DES) marker genes. Identity by descent (IBD) sib pair analysis
      using a three locus haplotype NRAMP1-IL8RB-VIL1, or NRAMP1 alone, provided
      preliminary evidence (maximum lod score = 1.01, p = 0.024) for a gene in this
      region contributing to suceptibility to rheumatoid arthritis. Candidacy for
      NRAMP1 as the disease susceptibility gene was supported by a significant bias (p
      = 0.048) towards transmission of the NRAMP1 promoter region allele 3 in affected
      offspring.

PMID- 8863161
TI  - PCR assay confirms diagnosis in syndrome with variably expressed phenotype:
      mutation detection in Stickler syndrome.
AB  - Stickler syndrome is an autosomal dominant disease with ocular (severe myopia,
      vitreal degeneration, and retinal detachment) and other systemic manifestations
      (hearing loss, cleft palate, epiphyseal dysplasia, and premature osteoarthritis).
      As with other dominantly inherited conditions, the clinical phenotype of Stickler
      syndrome varies considerably. To date, all mutations have been located in the
      type II procollagen (COL2A1) gene. Analysis of a C-->T mutation we had identified
      previously, in COL2A1 gene in exon 40, in a three generation pedigree showed the
      loss of a cleavage site for the TaqI restriction enzyme. We designed a rapid PCR
      based restriction enzyme assay to detect this mutation and used it to establish
      the diagnosis in a neonate from the same pedigree, presenting with the first
      occurrence of the Pierre-Robin sequence in the family and minimal ocular
      findings. These results underline the potential diagnostic value of many as yet
      undetected DNA mutations in families affected with Stickler syndrome, since the
      variability of the phenotype can impede accurate diagnosis, appropriate genetic
      counselling, and effective intervention and prophylactic treatment for affected
      people.

PMID- 8863162
TI  - Uneven X inactivation in a female monozygotic twin pair with Fabry disease and
      discordant expression of a novel mutation in the alpha-galactosidase A gene.
AB  - We describe two female monozygotic (MZ) twins heterozygous for Fabry disease, an
      X linked disorder resulting from the deficient activity of alpha-galactosidase A.
      While one of the twins was clinically affected, the other was asymptomatic.
      Enzymatic assay of alpha-galactosidase in blood leucocytes, skin fibroblasts,
      Epstein-Barr virus transformed lymphoid cell lines, and hair follicles of the
      twins and their parents confirmed the heterozygous status of the twins and
      indicated that Fabry disease had occurred as a result of a de novo mutation. The
      son of the unaffected twin sister was shown to be hemizygous. Molecular analysis
      of the alpha-galactosidase A gene permitted the identification of an as yet
      undescribed point mutation at position 10182 of exon 5 which causes an Asp to Asn
      substitution at codon 231. Single strand conformation polymorphism (SSCP)
      analysis again showed the heterozygous status of the twins and a normal pattern
      in their parents. The basis for the discordant expression of this d novo mutation
      in the twins was investigated by studying their X inactivation status. Analysis
      of the inactive X specific methylation at the androgen receptor gene showed
      unbalanced inactivation in the twins' fibroblasts and in opposite directions.
      While the maternally derived X chromosome was preferentially active in the
      asymptomatic twin, the paternal X chromosome was active in the other, affected
      twin and was found in her hemizygotic nephew. These data suggest that the
      paternal X chromosome carries the de novo alpha-galactosidase A mutation and that
      uneven X inactivation is the underlying mechanism for disease expression in this
      novel female MZ twin pair. This is the first documented case of female twins
      discordant for Fabry disease.

PMID- 8863163
TI  - Investigation of an interleukin-4 promoter polymorphism for associations with
      asthma and atopy.
AB  - The cytokine cluster located on chromosome 5 has been shown by linkage studies to
      play a role in the genetic determination of circulating immunoglobulin E (IgE)
      levels in atopic subjects. In the study presented here, the reported chromosome 5
      linkage has been investigated in two sets of subjects. The first consisted of a
      general population sample of 230 nuclear families (n = 1004) from Busselton, a
      small West Australian country town. The second group consisted of 124 unrelated
      atopic asthmatics and 59 unrelated non-atopic, non-asthmatic controls, all
      resident in the Oxfordshire Regional Health Authority area in the United Kingdom.
      A previously reported interleukin-4 (II-4) promoter polymorphism (-590 C-->T) was
      analysed in these populations by a newly designed method of specific PCR
      amplification and BsmFI restriction endonuclease digestion. In the Busselton
      population the polymorphism was shown to be weakly associated with specific IgE
      to house dust mite (Mann-Whitney-U test, p = 0.013) and to wheeze (MWU test, p =
      0.029), but not with specific IgE to grass pollen, total serum IgE, bronchial
      hyperresponsiveness, eosinophil count, or asthma. In the Oxfordshire subjects
      there were no statistically significant associations with any measure of asthma
      or atopy. These data show that the -590 C-->T II-4 promoter polymorphism is only
      weakly associated with certain measures of asthma and atopy in some subjects. It
      was specifically not associated with serum IgE concentration or asthma in either
      of the two groups in this study.

PMID- 8863165
TI  - X chromosome inactivation pattern in female carriers of X linked
      hypophosphataemic rickets.
AB  - X linked hypophosphataemia (XLH) results from an abnormality of renal tubular
      phosphate reabsorption. The disorder is inherited as an X linked dominant trait
      and the gene has been mapped to Xp22.1-p22.2. A candidate gene (PEX) has recently
      been isolated. The most striking clinical features are growth retardation and
      skeletal abnormalities. As expected for X linked dominant disorders, females are
      less affected. However, such a gene dosage effect does not exist for renal
      phosphate reabsorption. Preferential X chromosome inactivation has been proposed
      as a possible explanation for this lack of gene dosage. We have examined the X
      inactivation pattern in peripheral blood cells from 12 females belonging to seven
      families with XLH using PCR analysis at the androgen receptor locus. The X
      inactivation pattern in these patients did not differ significantly from the
      pattern in 30 healthy females. The X inactivation pattern in peripheral blood
      cells does not necessarily reflect the X inactivation pattern in renal cells.
      However, the finding of a normal distribution of X inactivation in peripheral
      blood cells indicates that the similarity in the renal handling of phosphate in
      male and female patients is not related to a ubiquitous preferential X
      inactivation.

PMID- 8863164
TI  - Rett syndrome.

PMID- 8863166
TI  - Gorlin syndrome associated with midline nasal dermoid cyst.
AB  - Gorlin syndrome is an autosomal dominant multisystem disorder characterised by
      multiple basal cell naevi, cysts of the jaw, pits of the palms and soles,
      skeletal anomalies, and various other defects. Patients with Gorlin syndrome have
      a predisposition to basal cell carcinomas and other neoplasms. This is the first
      report to describe the coexistence of Gorlin syndrome and a nasal dermoid cyst. A
      4 year old girl was diagnosed with medulloblastoma and treated with surgery and
      radiation therapy. A genetic evaluation was sought because of the brain tumour,
      multiple small naevi localised mostly on the upper torso, and rib abnormalities.
      Biopsies of several naevi showed naevoid basal cell carcinoma. Past medical
      history was significant for a midline nasal punctum noted at birth. The
      significance of this finding was unrecognised until the dermoid cyst enlarged,
      just before the diagnosis of her brain tumour. A common tissue of origin exists
      between basal cell naevi, cysts of the jaw, and dermoid cysts. We propose that
      the association of these two rare conditions in one patient is not a chance
      occurrence.

PMID- 8863167
TI  - Hidrotic ectodermal dysplasia of hair, teeth, and nails: case reports and review.
AB  - We report two families with the Witkop "tooth and nail syndrome". This term is a
      misnomer, as the hair was mildly involved in the original case reports and in the
      families reported here.

PMID- 8863168
TI  - Heterogeneity of phenotype in two cystic fibrosis patients homozygous for the
      CFTR exon 11 mutation G551D.
AB  - In the heterozygous state, the cystic fibrosis transmembrane conductance
      regulator (CFTR) exon 11 mutation G551D has been described as "severe," causing
      pancreatic insufficiency. Two cystic fibrosis (CF) patients homozygous for this
      mutation showed a mild rather than severe pancreatic phenotype and a variable
      pulmonary phenotype.

PMID- 8863169
TI  - Linkage of a medium sized Scottish autosomal dominant retinitis pigmentosa family
      to chromosome 7q.
AB  - Retinitis pigmentosa is a group of hereditary retinopathies which is both
      clinically and genetically heterogeneous. Autosomal dominant (ADRP), autosomal
      recessive (ARRP), and X linked recessive (XLRP), as well as digenic forms of
      inheritance have been reported. ADRP has been linked to 3q, 6p, 7p, 7q, 8cen,
      17p, 17q, and 19q. Three unrelated ADRP families have been reported to show
      linkage to 7q. We tested a Scottish ADRP family with microsatellite markers
      mapping within the 7q31-q35 region, and found three markers (D7S487, D7S514,
      D7S530) showing statistically significant evidence of linkage. A maximum two
      point lod score of 3.311 at 0% recombination was obtained for D7S514.

PMID- 8863170
TI  - Genotype-phenotype correlation in von Hippel-Lindau disease: identification of a
      mutation associated with VHL type 2A.
AB  - A family with von Hippel-Lindau disease (VHL) type 2A has been shown to have a T
      to C missense mutation at nucleotide 547 of the VHL gene. This gives further
      support for the proposal to associate the 547 T to C mutation with phenotype VHL
      2A.

PMID- 8863171
TI  - Prevalence of 22q11 microdeletion.

PMID- 8863172
TI  - Should the 3C (craniocerebellocardiac) syndrome be included in the spectrum of
      velocardiofacial syndrome and DiGeorge sequence?

PMID- 8863173
TI  - Health care reform and medical education.

PMID- 8863174
TI  - Occupational diseases-a mini review.

PMID- 8863175
TI  - Hemorrheologic effects of pyrimido-pyrimidine derivatives.
AB  - A series of pyrimido-pyrimidine derivatives were tested for their effect on
      membrane fluidity-deformability of human red blood cells and on human platelet
      aggregation. These agents were also tested for their intracellular cAMP
      increasing activity and proliferation inhibitory activity in neoplastic cells.
      The order of activity was established and clinical implications discussed.
      Several derivatives are under study as antineoplastic agents.

PMID- 8863176
TI  - Correlation between serum level of, and tissue positivity for, alpha-fetoprotein
      in hepatocellular carcinoma.
AB  - The serum level of alpha-fetoprotein (AFP) is a marker for primary liver tumors.
      To evaluate the relationship between the serum level of AFP and the positivity of
      liver tissue for this marker, specimens of liver were obtained at autopsy from
      patients with hepatocellular carcinoma (HCC). Tissues were fixed with formalin or
      Kryofix and immunostained for AFP. Serum AFP titer at autopsy was positively
      correlated with AFP staining in tissue fixed by Kryofix and stained with
      monoclonal antibody against AFP. The correlation was significant for plasma
      levels of AFP above 5,000 ng/ml. Results suggest that elevated serum AFP levels
      are an indicator of the progression of HCC.

PMID- 8863177
TI  - Changes in urinary enzyme activity and histochemical findings in experimental
      tubular injury induced by gold sodium thiomalate.
AB  - To elucidate the renal injury induced by gold treatment, we administered various
      doses of gold sodium thiomalate (GST) to Wistar rats and investigated alterations
      in the urinary enzyme activity, gamma-glutamyl transpeptidase (gamma GTP) and N
      acetyl-beta-glucosaminidase (NAG) activity, and histochemical change of enzymes,
      gamma GTP, alkaline phosphatase (ALP) and acid phosphatase (ACP) activity in the
      renal tissue. The single administration of a large dose of gold salts induced
      acute tubular necrosis and enzyme leakage was detected histochemically without
      damage to the glomerulus. After chronic administration of small doses of gold
      salts, the urinary gamma GTP activities gradually increased, but urinary NAG
      activities did not. These findings suggested that the change in urinary enzyme
      activities, which leaked from inside of brushborder or lysosome, indicated the
      degree or localization of tubular damage, because renal tubules were selectively
      injured by gold salts.

PMID- 8863178
TI  - Plasma levels of interleukin-1 receptor antagonist (IL-1ra) and severity of
      illness in patients with burns.
AB  - The present study was conducted to determine whether a plasma interleukin-1
      receptor antagonist (IL-1ra) would reflect the severity of burn injury and to
      examine the relation between IL-1ra and the cytokines. We studied 24 burn
      patients in whom the total burn surface area (TBSA) accounted for at least 20% of
      the body surface, and in whom serial blood samples could be obtained beginning
      immediately after the burn injury. Plasma levels of IL-1ra were determined by
      enzyme-linked immunosorbent assay (ELISA). Plasma levels of tumor necrosis factor
      alpha (TNF-alpha), IL-6, and IL-8 were also determined by ELISA. Endotoxin was
      measured by an endotoxin-specific synthetic substrate method. There was a
      significant correlation between the plasma levels of IL-1ra and TBSA during the
      first week following burn injury. The IL-1ra level was the highest immediately
      after the burn injury. The level decreased markedly thereafter, and again rose
      when infection occurred. The IL-1ra level was extraordinarily elevated in
      patients who developed concomitant sepsis, septic shock or the septic multiple
      organ dysfunction syndrome. The IL-1ra level on admission and the maximum IL-1ra
      level during the observation period were significantly higher in the patients who
      eventually died than in the survivors. There was a significant correlation
      between the level of IL-1ra and that of TNF-alpha, IL-6 or IL-8 during the
      observation period. No correlation was found between IL-1ra and endotoxin. The
      plasma IL-1ra level was closely correlated with the severity of inflammation and
      the clinical status of the burn patients, regardless of the infection. Results
      suggest that IL-1ra can serve as an index of the systemic inflammatory response
      syndrome (SIRS).

PMID- 8863180
TI  - Changes in baroreflex sensitivity induced by cilazapril do not manifest in
      Valsalva and tachycardia ratios in hypertensives.

PMID- 8863179
TI  - Vasodilator responses to desmopressin and its diluent, chlorobutanol, in the
      hindquarters vascular bed of the cat.
AB  - Desmopressin is a synthetic analog of vasopressin used to promote hemostasis and
      reduce postoperative blood loss. Recent studies have shown that desmopressin
      decreases arterial blood pressure in the anesthetized rat and relaxes isolated
      segments of aorta and pulmonary artery. Responses to a clinical preparation of
      desmopressin were investigated in the hindquarters vascular bed of the cat under
      constant flow conditions so that changes in perfusion pressure directly reflect
      changes in vascular resistance. Responses to desmopressin and its vehicle, and
      the effect of receptor antagonists, inhibitors of prostaglandin, and nitric oxide
      synthesis inhibitors, were investigated.

PMID- 8863181
TI  - Human 3 beta-hydroxysteroid dehydrogenase: genes and phenotypes.

PMID- 8863182
TI  - Dexamethasone modulates insulin receptor expression and subcellular distribution
      of the glucose transporter GLUT 1 in UMR 106-01, a clonal osteogenic sarcoma cell
      line.
AB  - Corticosteroids have profound effects on bone metabolism, though the underlying
      mechanisms remain unclear. They are also known to alter glucose metabolism, in
      part by induction of insulin resistance. To determine whether corticosteroids
      impair glucose metabolism in bone cells, we have examined the actions of
      dexamethasone (DEX) on glucose transport and insulin receptor expression using
      osteoblast-like UMR 106-01 cells. DEX was shown to inhibit basal 2-deoxyglucose
      uptake by up to 30% in a time- and dose-dependent manner. It inhibited insulin
      stimulated glucose transport by 13%. By Northern and Western blot analysis, DEX
      was shown to stimulate insulin receptor mRNA and protein by up to 5.6-fold, but
      it had no effect on expression of the glucose transporter GLUT 1 mRNA or protein
      under basal conditions. However, DEX augmented insulin-stimulated GLUT 1 mRNA and
      protein levels. By Scatchard analysis of labelled insulin binding, DEX increased
      insulin receptor number per cell by 54%. Subcellular fractionation and Western
      blot analysis demonstrated that DEX caused a redistribution of immunoreactive
      GLUT 1 from plasma membrane to intracellular microsomes, resulting in a 21%
      decrease in GLUT 1 at the plasma membrane. These data suggest that (i) DEX
      impairs basal glucose transport by post-translational mechanisms in UMR 106-01
      cells, (ii) DEX increases insulin receptor mRNA, protein and insulin binding and
      (iii) the inhibition of glucose transport by DEX dominates its effects on the
      insulin receptor. It is possible that DEX inhibition of glucose transport in
      osteoblasts may contribute to steroid-induced osteoporosis.

PMID- 8863183
TI  - Effects of sodium butyrate on glucose transporter and glucose-phosphorylating
      enzyme gene expression in RINm5F insulinoma cells.
AB  - RINm5F insulinoma cells show a defective physiological insulin secretory response
      to glucose stimulation. The short chain carbonic acid sodium butyrate induced a
      growth arrest during a 72-h tissue culture period. In contrast to control RINm5F
      cells, 2 mM glucose increased insulin secretion by more than 70% in these sodium
      butyrate-treated cells (1 mM) without any further increase of the secretory rate
      between 2 and 20 mM glucose. This effect of sodium butyrate on insulin secretion
      was assessed in comparison with its effect on gene expression of the GLUT1 and
      GLUT2 glucose transporter, hexokinase type I and type II, glucokinase and
      insulin. Sodium butyrate at a 1 mM concentration decreased GLUT1 gene expression
      by nearly 50%, but did not induce gene expression of the low-affinity GLUT2
      glucose transporter above the detection limit. Furthermore, sodium butyrate
      increased glucokinase gene expression by more than 50% and hexokinase type II
      gene expression by more than 100%, while insulin gene expression was increased
      only by 24%. Hexokinase type II enzyme activity was increased by more than 100%
      without a concomitant significant change of the glucokinase enzyme activity.
      Sodium butyrate (2 mM) caused effects comparable with those of 1 mM sodium
      butyrate. Thus the improved insulin secretory responsiveness of RINm5F insulinoma
      cells after sodium butyrate treatment at low non-physiological millimolar glucose
      concentrations can be interpreted as a result of an increased hexokinase-mediated
      metabolic flux rate through the glycolytic chain.

PMID- 8863184
TI  - Mistyping of the human angiotensin-converting enzyme gene polymorphism:
      frequency, causes and possible methods to avoid errors in typing.
AB  - A polymorphism of the gene encoding the human angiotensin I-converting enzyme
      (ACE), which is defined by an insertion/deletion polymorphism in intron 16, has
      been identified as a candidate genetic locus in the development of cardiovascular
      and renal disease. We have demonstrated that the accuracy of ACE genotyping is
      critically dependent on the strategy of the PCR used in typing. Of 1238
      individuals genotyped by a standard method, 335 were typed as DD, 645 as DI and
      258 as II. However, when DD individuals were retyped using modified methods
      (including either 5% dimethyl sulphoxide, or a 'hot start') 35 of the original
      335 samples (10.5%) were retyped as DI. In approximately half of these mistyped
      samples, PCR amplification was assessed as inefficient by the absence of a third
      faint heteroduplex band in a control ID sample: when the assay was repeated
      without any modifications, the mistyped samples were correctly genotyped. In the
      remainder, mistyping persisted. In these cases, the use of a third 'nested' PCR
      primer specific for the I allele was required for successful genotyping,
      providing a more reliable strategy without the need for further modification to
      the PCR technique. Our results suggest that the triple primer approach is the
      method of choice for accurate ACE genotyping.

PMID- 8863185
TI  - Identification and localisation of a type IV cytosolic phospholipase A2 in rat
      pancreatic beta-cells.
AB  - The liberation of arachidonic acid (AA), by phospholipase A2 (PLA2), is the rate
      limiting step in a number of cell signalling pathways. In the pancreatic beta
      cell, AA itself is thought to participate in the regulation of insulin secretion.
      Recently a Ca(2+)-sensitive, AA-selective cytosolic PLA2 (type IV cPLA2) has been
      isolated from the human monocyte U937 cell line. Although the DNA sequence of
      this enzyme implies a molecular weight of 85 kDa, the protein migrates with a
      molecular weight of 100-110 kDa on SDS-PAGE. In many cell types, cPLA2s which are
      reactive towards antibodies raised against the type IV cPLA2 have been shown to
      hydrolyse AA from membrane glycerophospholipids. Using a polyclonal antibody
      raised against a recombinant form of type IV cPLA2, we have detected an
      immunoreactive protein with a molecular weight of 93.5 kDa in rat islets of
      Langerhans. Furthermore, we have detected similar immunoreactive proteins in
      insulin-secreting beta-cell lines and have shown co-expression of type IV cPLA2
      immunoreactivity and insulin immunoreactivity in rat pancreatic beta-cells. Under
      non-stimulatory conditions the 93.5 kDa immuno-reactive protein detected in rat
      islets of Langerhans was located predominantly in the cytosolic fraction. We have
      shown that immunoprecipitation of the rat immunoreactive protein from rat islet
      homogenates significantly decreases the total dithiothreitol/beta-mercaptoethanol
      insensitive PLA2 activity by 56.4 +/- 7%. This provides further evidence that the
      immunoreactive rat protein is a type IV cPLA2 and is responsible for a large
      component of the PLA2 activity in rat islets of Langerhans. It is possible that,
      in the rat beta-cell, type IV cPLA2 couples the increase in intracellular Ca2+,
      brought about by insulin secretagogues, to the liberation of AA and the
      subsequent release of insulin.

PMID- 8863186
TI  - Expression of growth factor ligand and receptor genes in rat cancellous bone
      trabeculae and marrow.
AB  - The technique of reverse transcription-PCR for mRNA phenotyping was applied to
      total RNA isolated from the two compartments of cancellous bone, namely
      trabecular bone and hematopoitic tissue or marrow. The pattern of gene expression
      for ten different growth factor ligands and five growth factor receptors was
      examined in total RNA isolated from the two compartments of cancellous bone of
      the female rat distal femur. Our results show that transcripts encoding IGF-I,
      IGF-II, transforming growth factor-beta 1 (TGF-beta 1), TGF-alpha, basic
      fibroblast growth factor, platelet-derived growth factor A and osteocalcin are
      detectable in samples from both trabeculae and marrow. Expression of epidermal
      growth factor (EGF) was confined to samples from trabeculae while nerve growth
      factor expression was only detected in marrow. Transcipts encoding insulin were
      not detected in any of the bone-derived samples in this study. Samples from
      cancellous bone trabeculae and marrow both showed evidence of expression of the
      genes encoding receptors for IGF-I, parathyroid hormone (PTH)/PTH-related protein
      and insulin. Neither compartment of cancellous bone contained transcripts
      encoding the receptor for IGF-II. Transcripts encoding the EGF receptor were
      detected in samples from cancellous bone marrow and not trabeculae as has been
      previously reported. These patterns of growth factor ligand and receptor gene
      expression suggest that it is likely that both autocrine and paracrine regulatory
      circuits are established in cancellous bone. This study also demonstrated the
      feasibility of assessing the expression of multiple genes from the small samples
      of total RNA obtained from separated tissues of cancellous bone. This is the
      first time that growth factor gene expression has been examined in separated
      trabeculae and marrow from cancellous bone and this approach will allow a more
      detailed analysis of molecular events in cancellous bone as opposed to whole bone
      or extracts of isolated and cultured bone cells.

PMID- 8863187
TI  - Development of cytochrome P450 17 alpha-hydroxylase (P450c17) mRNA and enzyme
      activity in neonatal ovaries of normal and hypogonadal (hpg) mice.
AB  - The cytochrome P450 enzyme 17 alpha-hydroxylase (P450c17) is required for
      androgen synthesis and therefore regulates substrate supply for aromatization. In
      this study, changes in P450c17 activity and mRNA levels were measured during
      ovarian development in the normal mouse and in the hypogonadal (hpg) mouse which
      lacks circulating gonadotrophins. At birth, low levels of P450c17 activity and
      mRNA were detectable in normal ovaries. This basal level of expression did not
      change until after day 10 at which time both enzyme activity and mRNA levels
      increased by six- to eightfold. In the hpg mouse, levels of P450c17 mRNA were
      normal at birth but did not change significantly during subsequent development
      and were significantly less than normal by day 15. Results show that there is a
      low level of gonadotrophin-independent expression of P450c17 in the ovary at
      birth and that gonadotrophins are required for the subsequent increase in
      expression between days 10 and 15. In the ovary, P450c17 is expressed solely in
      the thecal/interstitial compartment and interstitial cells arise in the mouse
      ovary around day 11. Changes in P450c17 are likely, therefore, to be related to
      gonadotrophin-dependent development of the interstitial tissue in the mouse.
      Treatment of adult hpg mice with LH and FSH showed that both gonadotrophins can
      act to increase P450c17 activity. Since FSH acts only on the granulosa cell
      compartment of the ovary it is likely that FSH acts through a paracrine mechanism
      to regulate thecal/interstitial cell activity.

PMID- 8863188
TI  - Expression of activin beta C subunit mRNA in reproductive tissues.
AB  - A cDNA encoding the potential activin beta C subunit was produced from human
      testis RNA using reverse transcription and PCR and then used as a probe in
      Northern blot analysis of poly(A)+ RNA. A transcript of approximately 1.8 kb was
      evident in human ovary, placenta and testis samples. A transcript of this size
      was also detected in adult rat caput and cauda epididymis, and adult and day-15
      testis and adult spleen, while adult liver contained a single transcript of
      approximately 2.1 kb. Poly(A)+ RNA from primary spermatocytes but not from round
      spermatids contained the 1.8 kb activin beta C mRNA. These findings highlight the
      need for further studies to determine the physiological role(s) of activin beta C
      in a wide variety of tissues.

PMID- 8863189
TI  - Decreased muscle cell proliferation in chicks with a deletion in the GH receptor
      gene.
AB  - The increase in muscle weight in neonatal animals is a consequence of increased
      protein accretion and DNA content. GH increases protein accretion but direct
      effects of GH on myogenic cell proliferation have not been demonstrated. Sex
      linked dwarfism in the chick is caused by mutation or deletion in the GH receptor
      gene and has provided a useful model to study the physiological consequences of
      GH insensitivity. This study determined the consequences of GH receptor gene
      mutation on muscle cell proliferation in vivo. Northern and Southern blotting and
      PCR analysis revealed restriction fragment length polymorphism patterns and a 1.7
      kb deletion of the intracellular domain of the GH receptor gene in commercial
      dwarf broiler chicks, similar to the Connecticut strain in which there is a
      dysfunctional GH receptor. Cell proliferation was measured in muscle sections
      from normal and dwarf chicks after incorporation of 5-bromo-2'-deoxyuridine
      (BrdU; 25 mg/kg) in vivo at 2, 5 and 13 days of age. Incorporation of BrdU into
      nuclei was measured in frozen sections, counterstained with propidium iodide to
      estimate the total number of nuclei by quantitative image analysis, and the
      labelling index was calculated. Paraffin-embedded sections of breast muscle were
      stained using an anti-human IGF-I polyclonal antibody. Expression of IGF-I mRNA
      in muscle from each genotype at 5 days of age was measured by RNAse protection
      assay. The labelling index was similar in 2-day-old chicks from both genotypes
      (normal, 20.14 +/- 2.39%; dwarf, 19.79 +/- 5.83%). By day 5 the labelling index
      had decreased but was significantly higher (P < 0.02) in normal (12.53 +/- 3.36%)
      compared with the dwarf (6.25 +/- 1.39%). By 13 days of age, there was a further
      decrease in labelling index but no difference between the groups (normal, 4.92 +/
      1.28%; dwarf, 4.96 +/- 1.51%). IGF-I mRNA was expressed and IGF-I peptide was
      identified in muscle sections but there was no difference between genotypes. The
      results show that cell division in breast muscle in vivo is high in neonatal
      chicks but it declines with increasing age. The absence of a functional GH
      receptor in the dwarf is associated with a greater decline in DNA synthesis and
      suggests that GH may directly affect a proportion of cells, since there was no
      difference in IGF-I mRNA or peptide.

PMID- 8863190
TI  - Regenerating (reg) and insulin genes are expressed in prepancreatic mouse
      embryos.
AB  - The pancreatic regenerating (reg) gene is proposed to be involved in pancreatic
      beta-cell growth. Up- or down-regulation of reg gene expression has been shown to
      parallel variations in beta-cell mass and function in the adult pancreas. In
      several species at least two nonallelic reg genes have been identified. In this
      study we investigated the expression of each individual reg gene (reg-I and reg
      II) during embryogenesis in the mouse. Single mouse embryos were harvested at
      8.5, 9, 10, and 12 days of development, homogenized and subjected individually to
      reverse transcription (RT)-PCR, with a single primer pair to amplify both reg-I
      and -II mRNAs. Southern blot analysis of the RT-PCR products revealed the
      presence of reg mRNA at day 9 of embryogenesis, just before the beginning of
      pancreatic organogenesis. Slot-blot analysis with internal oligonucleotide probes
      that specifically recognize reg-I or -II sequences demonstrated that only reg-I
      mRNA was present in day 9 and day 10 prepancreatic embryos. Reg-II mRNA was not
      detected until day 12, a stage corresponding to late organogenesis. RT-PCR for
      insulin mRNA from the same samples used for the amplification of reg mRNA showed
      that the earliest insulin expression occurred at day 8.5, and coincided with the
      onset of reg-I expression. Hybridization with gene-specific oligonucleotide
      probes revealed that only insulin-II mRNA was detectable at this time. Insulin-I
      mRNA was not detectable until day 12 and coincided with early reg-II expression.
      These results suggest that the two nonallelic reg genes and the two insulin genes
      are expressed differentially during early embryogenesis. Differential expression
      of reg-I and -II suggests that they may be induced by different and independent
      stimuli and have distinct functions.

PMID- 8863191
TI  - MASCIS evaluation of open field locomotor scores: effects of experience and
      teamwork on reliability. Multicenter Animal Spinal Cord Injury Study.
AB  - The Multicenter Animal Spinal Cord Injury Study (MASCIS) adopted a modified 21
      point open field locomotor scale developed by Basso, Beattie, and Bresnahan (BBB)
      at Ohio State University (OSU) to measure motor recovery in spinal-injured rats.
      BBB scores categorize combinations of rat hindlimb movements, trunk position and
      stability, stepping, coordination, paw placement, toe clearance, and tail
      position, representing sequential recovery stages that rats attain after spinal
      cord injury. A total of 22 observers from 8 participating centers assessed 18
      hindlimbs of 9 rats at 2-6 weeks after graded spinal cord injury. The observers
      were segregated into 10 teams. The teams were grouped into 3 cohorts (A, B, and
      C), consisting of one experienced team from OSU and two non-OSU teams. The
      cohorts evaluated the rats in three concurrent and sequential sessions. After
      viewing a rat for 4 min, individual observers first assigned scores without
      discussion. Members of each team then discussed and assigned a team score.
      Experience (OSU vs. non-OSU) and teamwork (individual vs. team) had no
      significant effect on mean scores although the mean scores of one cohort differed
      significantly from the others (p = 0.0002, ANOVA). However, experience and
      teamwork significantly influenced reliability of scoring. OSU team scores had a
      mean standard deviation or discordance of 0.59 points, significantly less than
      1.31 points for non-OSU team scores (p = 0.003, ANOVA) and 1.30 points for non
      OSU individual scores (p = 0.001, ANOVA). Discordances were greater at the upper
      and lower ends of the scale, exceeding 2.0 in the lower (< 5) and upper (> 15)
      ends of the scale but were < 1.0 for scores between 4 and 16. Comparisons of non
      OSU and OSU team scores indicated a high reliability coefficient of 0.892 and a
      correlation index (r2) of 0.894. These results indicate that inexperienced
      observers can learn quickly to assign consistent BBB scores that approach those
      given by experienced teams, that the scores are most consistent between 4 and 16,
      and that experience improves consistency of team scores.

PMID- 8863192
TI  - Intrathecal infusion of the nitric oxide synthase inhibitor N-methyl L-arginine
      after experimental spinal cord injury in guinea pigs.
AB  - The potential role of nitric oxide (NO) production in secondary pathologic
      processes that follow spinal cord injury was examined in a guinea pig model that
      shows secondary loss of function for at least 3 days after trauma. Lateral
      compression injury of the lower thoracic cord was performed under
      ketamine/xylazine/acepromazine anesthesia. A fine polyethylene cannula was
      inserted through an incision in the dura rostral to the injury and run along the
      dorsal subdural space to the lesion level. The tube was connected to an osmotic
      pump delivering 1 microL/h of a 10 mM solution of either N-methyl-L-arginine or N
      methyl-D-arginine in normal saline (pH 7.2). N-Methyl-L-arginine blocks both
      constitutive and inducible forms of NO synthase (NOS), present in neurons and
      inflammatory cells, respectively: N-methyl-D-arginine is the inactive
      stereoisomer. Two groups of 10 animals were used. Behavioral analysis and
      somatosensory evoked potential measurements were performed daily for 3 days, then
      the animals were fixed and survival of white matter at the center of the injury
      was evaluated, using toluidine-blue stained, 1 microns plastic sections. No
      significant difference was found between treated and control groups in degree or
      rate of secondary loss of spinal cord function or in the cross-sectional area of
      surviving white matter. These data do not support the hypothesis that local NO
      production by phagocytes, neurons, or other cells plays a significant role in
      secondary pathology of injury in this model.

PMID- 8863193
TI  - Secondary insults increase injury after controlled cortical impact in rats.
AB  - Secondary ischemic insults are common after severe head injury and contribute to
      poor neurological outcome. To study the increased vulnerability of the
      traumatized brain to secondary insults, bilateral carotid occlusion was produced
      after a controlled cortical impact injury in rats. The injury produced by either
      the impact injury or the bilateral carotid occlusion was mild to moderate when
      studied individually. The 1 and 3 m/sec impact injuries alone caused no
      detectable contusion at the impact side and minimal neuronal loss in the
      hippocampus. The 5 m/sec impact injury alone resulted in a small contusion with a
      median volume of 5.4 mm3. The 40-min period of bilateral carotid occlusion alone
      caused no cortical injury and no neuronal loss in the CA1 region of the
      hippocampus. When the 40 min of bilateral carotid occlusion was produced 1 h
      after the impact injury, there was an increase in the damage produced. The
      contusion volume was significantly larger after the 3 and 5 m/sec impact injuries
      and the hippocampal neuronal loss was significantly greater after the 1 and 3
      m/sec impact injuries. When varying durations of bilateral carotid occlusion were
      produced 1 h after a 3 m/sec impact injury, contusion volume was significantly
      larger after bilateral carotid occlusion duration of 40 min, and CA1 neuronal
      loss was significantly greater after bilateral carotid occlusion durations of 30
      and 40 min. When 40 min of bilateral carotid occlusion was produced at different
      time intervals after a 3 m/sec injury, the increased contusion volume was maximal
      when bilateral carotid occlusion occurred at 4 h after the impact injury, and the
      increased neuronal loss in the CA3 region of the hippocampus was maximal when
      bilateral carotid occlusion occurred at 1 h after the impact injury. By 24 h
      after the impact injury, 40 min of bilateral carotid occlusion had minimal
      consequences, similar to the effect in sham-injured animals. These results mimic
      the clinical situation where secondary insults of a severity that would not cause
      permanent neurological damage in a normal person are associated with a marked
      worsening of neurological outcome after head injury and where the injured brain
      is most susceptible to secondary insults in the first few hours after injury.

PMID- 8863194
TI  - Reactive astrocytes in acute stage after experimental brain injury: relationship
      to extravasated plasma protein and expression of heat shock protein.
AB  - It is well known that an astrocytic response occurs after brain damage; however,
      the mechanisms initiating this acute astrocytic response remain unclear. In this
      study, we examined the immunolocalization of glial fibrillary acidic protein
      (GFAP) to investigate the astrocytic response within 72 h after injury. Further,
      we related these results to the distribution of extravasated plasma protein and
      the expression of stress protein. Adult male Wistar rats were subjected to a
      lateral fluid percussion brain injury. Animals were sacrificed at 1, 6, 24, and
      72 h postinjury. Each brain section was immunostained for GFAP, extravasated
      albumin, and heat shock protein (HSP 72). Immunoreactive astrocytes, extravasated
      albumin, and HSP 72 positive cells were evaluated by light microscopy. Reactive
      astrocytes were defined by the presence of increased immunoreactivity to anti
      GFAP. By 6 h, the presence of reactive astrocytes was restricted to the impact
      site and the hemorrhagic external capsule. At 24 h, reactive astrocytes were
      identified in the entire injured hemisphere. By 72 h, the immunoreactive
      astrocytes were more pronounced than at 24 h. At 1 h, extravasated albumin was
      found at the impact site, the hemorrhagic external capsule, the parasagittal
      cortex, hippocampus, thalamus, and midbrain. By 72 h, the immunostaining of
      albumin was more widely distributed. HSP 72 immunoreactive glia were detected
      only at the impact site and the hemorrhagic external capsule. In summary, the
      distribution of reactive astrocytes at 6 h was associated with HSP 72-positive
      glia rather than the extravasation of albumin. In contrast, the distribution of
      reactive astrocytes at 24 and 72 h paralleled that of extravasated albumin. These
      results suggest that the initial response of astrocytes is correlated to glial
      stress and/or injury and that humoral factors play a role in the subsequent
      responses.

PMID- 8863195
TI  - Acute alterations in [Ca2+]i in NG108-15 cells subjected to high strain rate
      deformation and chemical hypoxia: an in vitro model for neural trauma.
AB  - The short-term (less than 2 min) alterations in the intracellular free calcium
      concentration in differentiated NG108-15 (neuroblastoma cross glioma) cells
      exposed to dynamic mechanical deformation with and without superimposed chemical
      hypoxia were determined. A previously developed device, modified for these
      studies, was used to apply deformations at a magnitude and rate representative of
      those experienced by neural tissue in Traumatic Brain Injury. Chemical hypoxia
      was imposed using a combination of 2-deoxy-D-glucose and salicylate, anaerobic
      and aerobic metabolic blockers, respectively. Real time measurement of
      intracellular free calcium concentration using Fura-2 and a custom
      epifluorescence microscopy system provided a quantitative index of cell response.
      At high rates of deformation (approximately 10 sec-1), increases in intracellular
      free calcium concentration were exponentially related to the magnitude of the
      applied deformation. Chemical hypoxia had no effect on this acute response. At
      low rates of deformation, small increases in intracellular free calcium
      concentration were independent of the magnitude of the deformation. These
      findings indicate that strategies for reducing severity of TBI should focus on
      minimizing the rate of deformation of neural cells. Together with data from
      animal, physical, and finite element models, these data can be employed in the
      development of physiologic injury tolerance criteria for the whole head.

PMID- 8863196
TI  - Kinematic analysis of limb position during quadrupedal locomotion in rats.
AB  - A test of locomotor behavior using the coordinates of ipsilateral limb positions
      of rats walking on a moving treadmill is described. Specific points on the
      forelimb and hindlimb were digitized from video records for 20-sec continuous
      sequences of locomotion, and step periods and step distances were calculated. The
      extent to which a given limb position would predict its own position--or the
      position of another limb--at different points in time was mathematically
      determined by autocorrelation and cross-correlation, respectively.
      Autocorrelation of position data was performed using a three-step window and the
      standard formula for correlating phasic data. A novel method of data preparation,
      which included normalization of the step data to eliminate variability introduced
      by differences in step period length, was used prior to cross-correlations of
      forelimb to hindlimb positions. Rats walking at 0.10, 0.15, and 0.25 m/sec had
      high limb autocorrelations, comparable forelimb/hindlimb phase relationships, and
      consistently high average cross-correlation coefficients. This analysis has
      resulted in the quantification of rat locomotor behavior in terms of the degree
      of limb movement rhythmicity and the strength of the forelimb/hindlimb
      coordination, and has provided baseline data for comparisons with spinal cord
      injured rats that have retained or recovered alternating hindpaw movements.

PMID- 8863197
TI  - Mutant p53 protein as a biomarker of chemical carcinogenesis in humans.

PMID- 8863198
TI  - Lung cancer mortality among workers in formaldehyde industries.

PMID- 8863199
TI  - A cognitive-behavioral treatment of patients suffering from "electric
      hypersensitivity". Subjective effects and reactions in a double-blind provocation
      study.
AB  - This study tested psychological treatment of patients with "electric
      hypersensitivity." Seventeen patients were randomly assigned to a treatment group
      or a waiting-list control group in a pretest-posttest control group design. The
      patients were also taking part in double-blind provocation tests before and after
      the treatment. Subjective ratings of symptoms were registered and blood samples
      were taken and analyzed for "stress-related" variables, such as prolactin,
      cortisol, dehydroepiandrosterone, and cholesterol levels. The patients in the
      experimental group reduced their evaluations of the disability more than the
      control group did. This indicates that psychological treatment may be of value in
      this disease. However, none of the psychophysiological measures or the subjective
      reactions to the provocation test showed any significant between-group
      difference. The conclusion from the provocation test is that this group of
      alleged hypersensitive patients did not react to the electromagnetic fields.

PMID- 8863200
TI  - Occupational exposure of water-plant operators to high concentrations of radon
      222 gas.
AB  - Water-plant operators may be exposed to high airborne radon-222 (222Rn)
      concentrations created when 222Rn gas transfers from water to air during the
      water treatment processes. To evaluate this hazard, we placed yearlong alpha
      track radon detectors in 31 water plants. The geometric mean of the annual
      average airborne 222Rn concentrations was 3.4 pCi L-1 (126 Bq m-3), with a
      maximum of 133 pCi L-1 (4921 Bq m-3). We assessed the short-term temporal
      variability of 222Rn by monitoring four water plants continuously for a 3- to 6
      day period. Cumulative working level months were estimated for the time workers
      were in the water plants. Because airborne 222Rn concentrations in water plants
      can reach levels considered unsafe for underground miners, it would be prudent to
      monitor airborne 222Rn concentrations in water plants which aerate water as part
      of their treatment process.

PMID- 8863201
TI  - A medical-center-wide, multidisciplinary approach to the problem of natural
      rubber latex allergy.
AB  - Latex is a common cause of occupational allergy in health care workers; latex
      sensitized patients are at increased risk of allergic reactions in medical
      environments. Skin test reagents and latex-specific immunoglobulin E immunoassays
      were established for diagnosis of latex allergy. Inhibition immunoassays were
      developed for measuring latex aeroallergens and latex allergens in rubber
      products. A registry of latex-sensitive employees was established. High-allergen
      gloves were removed from the medical center inventory; latex aeroallergen levels
      subsequently declined. Despite an increasing number of gloves used annually,
      expenditures for gloves in 1994 were lower than in previous years. Latex
      sensitive individuals can be identified using skin tests or immunoassays. Latex
      aeroallergen levels in medical environments can be reduced substantially at lower
      cost by using powder-free rubber gloves with lower allergen content.

PMID- 8863202
TI  - Study of employees with anhydride-induced respiratory disease after removal from
      exposure.
AB  - The purpose of this study was to determine the clinical and immunologic status of
      hexahydrophthalic anhydride (HHPA)-exposed employees who had developed an
      immunologic respiratory disease and who have been removed from exposure for at
      least 1 year. In a surveillance study spanning 4 years, we identified 28
      employees with HHPA-induced immunologic respiratory disease who had been removed
      from exposure for at least 1 year. Seven had asthma, nine had hemorrhagic
      rhinitis, four had both, and eight had allergic rhinitis alone. Respiratory
      symptoms were assessed by physician-administered questionnaires. For each
      employee, a physical examination, spirometry, and chest roentgenograph were
      performed. Antibody against HHPA conjugated to human serum albumin (HHP-HSA) was
      measured using an enzyme-linked immunosorbent assay. Symptoms, signs, and
      spirometry normalized in all but one employee. There were no chest-roentgenograph
      findings at follow-up that could be attributed to HHPA. There was a decline in
      antibody liter for both immunoglobulin E and G against HHP-HSA. In this group of
      28 employees, there was only one employee with mild asthma after removal from
      exposure for at least I year. Although specific antibody was still present in
      many, the titers were generally lower at follow-up than at presentation.

PMID- 8863203
TI  - Monitoring of exposure to benomyl in nursery workers.
AB  - We compared urinary levels of the metabolite methyl-5-hydroxy-2-benzimidazole
      carbamate (5-HBC) among nursery workers exposed to the fungicide benomyl
      (specifically Benlate 50 DF [DuPont, Wilmington, DE]) and workers not exposed to
      benomyl. Environmental exposures were quantitated from gloves, body patches, and
      air samples collected with area and personal monitors. The median concentration
      of 5-HBC in the urine of benomyl-exposed workers was 23.8 mumol of 5-HBC per mole
      of creatinine. No 5-HBC was detected in the reference group. Industrial hygiene
      results and biological monitoring findings indicate that use of Benlate 50 DF in
      the ornamental industry can lead to absorption of the active ingredient, benomyl.
      Weighing, mixing, and application activities involved the highest exposures.
      Dermal contact appeared to be the primary route of exposure.

PMID- 8863205
TI  - Pesticide poisonings in the lawn care and tree service industries. A review of
      cases in the New York State Pesticide Poisoning Registry.
AB  - Although pesticides are used extensively by lawn care and tree service workers,
      the incidence of pesticide poisonings among this population has never been
      systematically assessed. This article is a review of suspected and confirmed
      pesticide poisonings of lawn care and tree service applicators that were reported
      to the New York State Pesticide Poisoning Registry from 1990 to 1993. Thirty-nine
      cases were identified, of which 28 satisfied the criteria for a suspected or
      confirmed poisoning. At the time of the poisoning, the majority of applicators
      reported the use of more than one class of pesticide. The most common classes of
      pesticide applied were organophosphates (71%) and herbicides (43%). Twenty-four
      cases were identified through laboratory reporting. All 24 laboratory tests had
      been ordered for worker surveillance. Twenty of the reported workers were
      symptomatic. Personal protective equipment was used routinely by 22 of the 27
      applicators for whom information was available. These data suggest that pesticide
      exposures are occurring among a subset of the lawn care and tree service
      applicators, despite the reported routine use of safety measures. More rigorous
      evaluation of the control measures utilized in the lawn care and tree and shrub
      industry is warranted.

PMID- 8863204
TI  - A population-based study of tractor-related injuries: Regional Rural Injury Study
      I (RRIS-I).
AB  - Although tractors account for the majority of fatal farming-related injuries,
      little is known about the magnitude of this problem. The study population in this
      article was obtained from the five state Regional Rural Injury Study-I (RRIS-I)
      database that included 3939 farm households and 13,144 persons interviewed during
      1990. Rates were calculated for sociodemographic variables and various exposures;
      logistic regression was used to calculate the relative risks and respective
      confidence intervals. Among the total farming-related injury events (n = 764), 65
      (8.4%) were related to regular tractor (> or = 20 horsepower) use (495 injured
      persons per 100,000 persons per year). The rates increased incrementally for
      those persons working between 20 to 39 and 60 to 79 hours per week (range, 529 to
      1430 per 100,000 persons). Among the 12 rollover events, there were only three
      injuries. The majority of injury events occurred while persons were mounting or
      dismounting the tractor (42%). Although only 7% of the cases were hospitalized,
      83% required some type of health care. Among all injured persons, 43% were
      restricted from regular activities for 1 week or more and 20% were restricted for
      1 month or more; 28% continued to have persistent problems. The finding of the
      large proportion of events associated with activities of mounting and dismounting
      suggests a need to investigate specific design characteristics of the tractors
      associated with these events and, in general, the tractors to which the
      population is exposed.

PMID- 8863206
TI  - Oral carcinogens.

PMID- 8863208
TI  - Glottic microinvasive carcinoma: is it different from carcinoma in situ?
AB  - OBJECTIVE: To determine the impact of different treatment modalities on the
      outcome of microinvasive carcinoma. DESIGN: Retrospective review of patients
      presenting between 1976 and 1990. SETTING: Fifteen patients with microinvasive
      carcinoma (MIC) of the glottic larynx treated at McGill University teaching
      hospitals. METHODS: All patients had MIC involving the glottis confirmed
      pathologically. Nine patients (60%) had right vocal cord involvement, four (27%)
      had left vocal cord involvement, and two (13%) had involvement of both cords.
      Five patients (33%) were treated by stripping(S), three patients (20%) by
      stripping and radiotherapy (S + RT), and six patients (40%) by radiotherapy (RT)
      alone as the primary treatment. Only one patient underwent hemilaryngectomy.
      RESULTS: With a median follow-up time of 63 months (range 20-208 months), the 15
      year actuarial survival rate is 100% for all patients. CONCLUSIONS: Surgery
      alone, RT alone, or S + RT is equally effective in treating MIC of the glottic
      larynx; however, single-modality therapy is preferred. The choice of treatment
      modality should be individualized for each patient.

PMID- 8863207
TI  - Value of rigid bronchoscopy and cytodiagnosis of bronchial washings in detecting
      bronchial carcinoma in the presence of a carcinoma of the upper aerodigestive
      tract.
AB  - OBJECTIVE: To assess the usefulness of rigid bronchoscopy and bronchial washings
      in detecting primary lung carcinomas. SETTING: Department of Otolaryngology,
      University Hospital of Ghent, Belgium. DESIGN: Prospective analysis of patient
      investigations. METHOD: The results of 127 rigid bronchoscopies with bronchial
      washings in patients with a new, untreated head and neck tumour and a normal
      chest radiograph were analyzed for their usefulness in detecting simultaneous
      primary lung carcinomas. All patients were followed for a minimum of 2 years or
      till death. RESULTS: We found positive bronchial washings in 19 cases (21%).
      Unilateral positive bronchial washings were found in 8 patients (9%). In only one
      patient was a simultaneous primary lung tumour found. One patient was found to
      have a pulmonary metastasis. The remaining 6 patients with positive unilateral
      cytology (6/8) had normal chest roentgenograms and/or CT scans, and did not
      develop a lung tumour in the course of follow up. Of the 19 positive bronchial
      washings, 10 patients had a carcinoma of the larynx and two had a large
      hypopharyngeal carcinoma. CONCLUSIONS: Contamination of bronchial washings with
      tumour cells from head and neck neoplasms limited seriously the usefulness of
      positive bronchial cytology. The sensitivity and specificity of the rigid
      bronchoscopy with bronchial washing is too low to justify its cost.

PMID- 8863209
TI  - Deep-neck space abscesses.
AB  - OBJECTIVE: Despite a reduction in the incidence, deep-neck space infections are
      still seen today with definite potential for significant morbidity and even
      mortality. DESIGN: The authors present their experience in the management of 16
      patients with 19 deep-neck space abscesses. The distribution of the abscesses
      were: 5 Ludwig's angina, 4 parapharyngeal abscesses, 3 retropharyngeal abscesses,
      3 in the sub-mandibular triangle, 3 in the deep anterior triangle, and 1 in the
      deep posterior triangle. RESULTS: The source of infection was odontogenic in six
      patients, pharyngeal in three, otogenic in one, and could not be identified in
      the other six patients. Most cases presented with pain and neck swelling. Plain x
      ray films, computed tomography, ultrasonography, and magnetic resonance imaging
      were the main diagnostic procedures. Positive culture was obtained in only nine
      cases (56.2%). No predominant single organism was identified. Antimicrobial
      therapy and surgical drainage were the mainstay of treatment. Two cases were
      complicated by internal jugular-vein thrombophlebitis. All the patients survived
      without major residual sequelae. CONCLUSIONS: The etiology, presentation, and
      management of deep-neck space infections are briefly reviewed.

PMID- 8863210
TI  - Comparison of laser-assisted uvulopalatopharyngoplasty to electrocautery-assisted
      uvulopalatopharyngoplasty: a clinical and pathologic correlation in an animal
      model.
AB  - OBJECTIVE: To determine if there are any pathologic or technical differences
      between laser-assisted uvulopalatopharyngoplasty (LAUP) and electrocautery
      assisted uvulopalatopharyngoplasty (EAUP). DESIGN: A prospective randomized in
      vivo trial in an appropriate animal species. RESULTS: We found no gross
      difference in healing between the palates treated with laser and those treated
      with high-frequency electrocautery. However, there was consistently more thermal
      damage noted histologically in the hemipalates treated with LAUP. On the other
      hand, EAUP was faster to perform, more hemostatic, associated with less char
      formation, and had less histologic evidence of thermal damage. CONCLUSIONS: These
      results raise the possibility that the beneficial effects of LAUP over
      traditional uvulopalatopharyngoplasty (UPPP) may be as a consequence of staging
      rather than the particular treatment modality used.

PMID- 8863211
TI  - Objective identification of dizzy patients by vestibulo-ocular and
      vestibulospinal testing.
AB  - OBJECTIVE: To evaluate how well two new objective tests of vestibular function
      might help identify truly dizzy patients. DESIGN: A prospective study of dizzy
      patients. SETTING: Department of Otolaryngology, Sir Mortimer B. Davis-Jewish
      General Hospital, Montreal, Quebec. METHODS: Vestibular function (in 39 dizziness
      clinic patients and 30 normals) was characterized as follows: 1. While subjects
      sat on a rotatable chair trying to look at a wall target, vestibulo-ocular
      function was quantified by accuracy of ocular stabilization during brief chair
      turns imposed during 1-second periods of darkness. 2. While subjects stood feet
      together rotating their head and torso together from the knees, vestibulospinal
      function was quantified by the fastest comfortable torsal-head movement made
      without exacerbating dizziness. RESULTS: After plotting ocular stabilization
      accuracy against fastest comfortable torsal-head velocity, patients and normals
      tended to separate into two groups. Statistical analysis permitted most dizzy
      patients (sensitivity: 87%), and most normals (specificity: 83%) to be
      identified. CONCLUSION: Results are promising, since approximately 40% of
      patients had no abnormal vestibular signs.

PMID- 8863212
TI  - Particle repositioning maneuver: effective treatment for benign paroxysmal
      positional vertigo.
AB  - OBJECTIVE: To assess short-term and long-term outcomes of the particle
      repositioning maneuver (PRM). DESIGN: This is a prospective study of 68 cases of
      benign paroxysmal positional vertigo (BPPV) in 65 consecutive patients. RESULTS:
      Initially, 57 (83.8%) cases had no evidence of residual symptoms, 10 (14.7%) had
      a partial improvement, and only 1 (1.5%) failed treatment. In the long-term (18.7
      month mean follow-up period), 43 (67.2%) cases had no history of recurrence, and
      22 (34.4%) cases had recurrences, of which 14 (21.9%) experienced only mild
      symptoms, and 8 (12.5%) were no better than before the PRM. Of the eight who were
      no better, five had repeat PRMs that successfully relieved their symptoms. The
      final overall outcome was that 59 (95.2%) patients had either mild symptoms or no
      symptoms, and 3 (4.8%) patients were treatment failures. Factors that did not
      seem to be predictive of outcome were secondary nystagmus, gender, and duration
      of symptoms. In both the short and long terms, the self-limited form of BPPV was
      found to have the best outcome, the episodic type had an intermediate outcome,
      and the prolonged type had the worst outcome. CONCLUSIONS: We postulate that
      outcomes are best in those cases where free-floating canaliths are the mechanism
      of disease, which includes patients with self-limited BPPV. Patients with
      episodic or prolonged BPPV may have varying degrees of underlying cupulolithiasis
      that cannot be entirely corrected with PRM alone.

PMID- 8863213
TI  - Microbiology and management of sinusitis.
AB  - PURPOSE: The pathophysiology, microbiology, and treatment of acute and chronic
      sinusitis are reviewed. MATERIALS AND METHODS: The current literature is
      reviewed. REVIEW: Sinusitis generally develops as a complication of viral or
      allergic inflammation of the upper respiratory tract. Bacterial pathogens
      contribute to the inflammatory process-Streptococcus pneumoniae, Haemophilus
      influenzae, and Moraxella catarrhalis are predominant in acute sinusitis, while
      anaerobic bacteria and Staphylococcus aureus are predominant in chronic
      sinusitis. Pseudomonas aeruginosa has emerged as a potential pathogen in the
      immunocompromised patients and in those who have nasal tubes or catheters. Many
      of these organisms recovered from sinusitis became resistant to penicillins
      either through the production of beta-lactamase (H. influenzae, M. catarrhalis,
      S. aureus, Fusobacterium sp., and Prevotella sp.) or through changes in the
      penicillin-binding protein (S. pneumoniae). The pathogenicity of beta-lactamase
      producing bacteria is expressed directly through their ability to cause
      infections, and indirectly through the production of beta-lactamase. CONCLUSIONS:
      The indirect pathogenicity is conveyed not only by surviving penicillin therapy,
      but also by "shielding" penicillin-susceptible pathogens from the drug. The
      direct and indirect virulent characteristics of these bacteria require the
      administration of appropriate antimicrobial therapy directed against all
      pathogens in mixed infections. Proper therapy, with antimicrobial and
      decongestants combined when indicated with surgical drainage and correction of
      pathology, constitutes the cornerstone of management of sinusitis.

PMID- 8863214
TI  - External septoplasty in children.

PMID- 8863215
TI  - Multiple endocrine neoplasia type 1: an interesting Canadian pedigree.

PMID- 8863216
TI  - Multiple dentigerous cysts in childhood.

PMID- 8863217
TI  - Acute macroglossia causing upper-airway obstruction.

PMID- 8863218
TI  - Giant sinus as a possible risk factor of postoperative pneumocephalus: a case
      report.

PMID- 8863219
TI  - Eosinophilic angiocentric fibrosis of the subglottic region of the larynx and
      upper trachea.

PMID- 8863220
TI  - History of otolaryngology in Canada, the University of Toronto: Part 2.

PMID- 8863221
TI  - Early history of the therapy of Hirschsprung's disease: facts and personal
      observations over 50 years.

PMID- 8863222
TI  - Selective inhibition of the inducible isoform of nitric oxide synthase prevents
      pulmonary transvascular flux during acute endotoxemia.
AB  - The inducible isoform of nitric oxide synthase (iNOS) is expressed in various
      organs, including the lung, during systemic endotoxemia. Overproduction of nitric
      oxide (NO) by iNOS contributes significantly to the vascular failure and end
      organ damage in endotoxemia. Using selective pharmacological inhibitors of iNOS,
      the purpose of this study was to define the role of iNOS in a rat model of
      endotoxin-induced pulmonary transvascular flux (TVF). Lung TVF was assessed by a
      method of Evans Blue permeability index (PI). Bacterial lipopolysaccharide (LPS)
      (15 mg/kg intraperitoneally [IP]) significantly increased pulmonary iNOS activity
      and serum levels of nitrite/nitrate (NO2/NO3). This was accompanied by a
      significant elevation of the PI 5 hours after injection. Selective iNOS
      inhibition with either S-methyl isothiourea (SMT; 5 mg/kg IP) or aminoguanidine
      (AG; 20 mg/kg IP), administered 2 hours after LPS injection, significantly
      prevented the increase in PI associated with LPS injection. Similarly, inhibition
      of the induction of iNOS with dexamethasone (10 mg/kg IP), given 3 hours before
      LPS, also inhibited the increase in PI. All three treatments significantly
      prevented the increase in both lung iNOS activity and serum NO2/NO3 associated
      with endotoxemia. In conclusion, the overproduction of NO generated by iNOS
      during systemic endotoxemia causes a vascular leak in the lung. Thus, it is
      speculated that selective inhibition of iNOS may be beneficial in preventing the
      development of acute respiratory failure in sepsis.

PMID- 8863223
TI  - Decreased pulmonary nitric oxide synthase activity in the rat model of congenital
      diaphragmatic hernia.
AB  - Because nitric oxide (NO) dilates vascular smooth muscle cells, a deficiency of
      endogenous pulmonary nitric oxide production by nitric oxide synthase (NOS) has
      been suggested to be involved in the pathophysiology of pulmonary hypertension in
      congenital diaphragmatic hernia (CDH). Our aim was to determine whether
      experimentally induced CDH in rats results in a decrease in the synthesis of NO
      in the lungs. Adult Sprague-Dawley rats were fed 300 mg/kg of nitrofen at 10.5
      days' gestation. CDH, control, and sham (dosed with nitrofen, but without CDH)
      lungs were homogenized at full term (22 days' gestation) for measurement of NOS
      activity using the 14C-L-arginine to 14C-L-citrulline conversion assay. Western
      blot analysis with anti-endothelial cell NOS (EC-NOS) monoclonal antibody (mAb)
      was performed, and NOS expression was measured by densitometry. NOS activity was
      highest in the pulmonary parenchyma of control rat lungs (0.420 +/- 0.20
      fmol/min/mg lung; n = 11), intermediate in sham lungs (0.370 +/- 0.010
      fmol/min/mg lung; n = 14), and lowest in CDH lungs (0.300 +/- 0.04 fmol/min/mg
      lung; n = 12). NOS activity in the CDH and sham lungs was significantly lower
      than that of control lungs (P < .05). There was no difference in pulmonary NOS
      activity between sham and CDH lungs. NOS protein expression by Western blot
      analysis paralleled the observation for NOS activity in all groups, with the
      highest concentrations in controls, intermediate expression in sham lungs, and
      lowest expression in CDH lungs. Both NOS expression and NOS activity are
      significantly decreased in CDH rat lungs. Pulmonary hypertension in this model
      may be attributable to a deficiency of endogenous NO. This is the first reported
      study to suggest that decreased NOS activity may result in pulmonary hypertension
      in CDH.

PMID- 8863224
TI  - Renal salvage procedures in patients with synchronous bilateral Wilms' tumors: a
      report from the National Wilms' Tumor Study Group.
AB  - Synchronous bilateral Wilms' tumor accounts for 4% to 6% of all Wilms' tumors.
      Renal salvage procedures (partial nephrectomy and enucleation) have been
      recommended to conserve renal parenchyma. The objective of this study was to
      review the results of renal salvage operations performed in children who had
      bilateral neoplasms. The authors reviewed the records of 98 children enrolled in
      the Fourth National Wilms' Tumor Study who had synchronous bilateral tumors and
      underwent renal salvage procedures. One hundred thirty-four kidneys were managed
      with renal salvage procedures. Complete excision of gross disease was
      accomplished in 118 (88%) of the 134 kidneys. Local tumor recurrence in the
      remnant kidney or tumor bed occurred in 11 cases (8.2%). Overall, 72% of the
      kidneys were preserved, and the 4-year survival rate was 81.7%. The surgical
      morbidity after a salvage procedure was comparable to that of a complete
      nephrectomy in patients with unilateral Wilms' tumor. Although the incidence of
      positive surgical margins is worrisome, it did not invariably lead to local
      recurrence in the remnant kidney or the tumor bed.

PMID- 8863225
TI  - Esophageal replacement using the colon: is it a good choice?
AB  - Thirty-eight children (2 months to 26 years of age) underwent esophageal
      replacement at our institution between 1962 and 1993. Twenty-four patients had
      esophageal atresia, with the replacement performed at a mean age of 17 months.
      The remaining patients (37%) had strictures and were older (mean, 7.4 years).
      Replacement procedures involved the right colon in 61% of cases and the
      transverse left colon in the others (39%). Sixty-three percent were placed
      substernally and 37% were done in transthoracic fashion. The average length of
      stay in the hospital was 34 days (range, 11 to 256 days.) Early complications
      (within 30 days) included cervical anastomotic leaks (11 patients; 29%) pneumonia
      (4), would infection (2), pneumothorax/hemothorax (3), wound dehiscence (1),
      prolonged ventilation (2), vocal cord paralysis (1), Horner's syndrome (1),
      pancreatitis (1), and perforated graft (1). Despite the incidence of early leaks,
      only two persisted long-term (more than 3 months). Other late complications
      included significant proximal strictures (5), and cologastric strictures
      developed in five patients. Seven cases were considered graft failures (18%), and
      all of these eventually require graft replacement. Additional problems included
      redundant graft requiring revision (4) and dumping syndrome (2). There were six
      cases of intestinal obstruction caused by adhesions. Four of these involved
      intrathoracic obstruction of the graft and two involved small bowel obstruction.
      There was only one death, which occurred late and was not related to the primary
      disease or procedure. Long-term follow-up data were available for 20 patients
      (53%). The follow-up period ranged from 1 to 33 years (mean, 12 years). Fourteen
      had excellent results after the initial interposition, being able to eat and
      function well without any further intervention. Seven patients (18%) have had
      poor results and 17 (45%) required additional procedures to obtain good
      functional results. In our experience, the colon continues to be a good option
      for esophageal replacement, but additional procedures frequently are necessary to
      optimize the functional outcome. Good results can be expected in the majority of
      cases, but late problems (ie, redundant colon and poor emptying) are not unusual,
      and careful follow-up is essential in the management of such patients.

PMID- 8863226
TI  - Insurance-related differences in the presentation of pediatric appendicitis.
AB  - In the pediatric population, there is strong evidence to suggest that a delay in
      treatment results in an increased risk of appendiceal perforation. However, it is
      not clear whether this delay arises from the parent seeking medical advice, the
      referring physician seeking surgical consultation, or the surgeon deciding to
      operate. To resolve this issue, the authors performed a retrospective chart
      review of all cases of confirmed acute appendicitis that presented to the
      pediatric surgical service of the Children's Hospital of Buffalo during a 4-year
      period (January 1990 through December 1993). All children (< or = 16 years of
      age) were categorized with respect to type of insurance coverage:Medicaid (or
      uninsured), health maintenance organization (HMO), or private fee-for-service.
      Their time until emergency room (ER) presentation, operating room (OR)
      presentation, and hospital discharge were recorded and compared. Their
      complications and perforation rates also were noted. Two hundred eighty-eight
      cases were reviewed. The rate of appendiceal perforation was significantly higher
      among the Medicaid patients (Medicaid, 44%; HMO, 27%; private, 23%; P < .05);
      their duration of symptoms before presentation was significantly longer
      (Medicaid, 47.3 +/- 4.1 hours; HMO, 29.3 +/- 1.9 hours; private, 23.1 +/- 2.5
      hours; P < .01), and their hospital stay was longer (Medicaid, 7.9 +/- 0.9 days;
      HMO, 4.8 +/- 0.27 days; private, 4.6 +/- 0.44 days; P < .01). However, there were
      no significant differences in the time from presentation to the ER until
      definitive surgery in the OR. Children covered by Medicaid (or uninsured)
      presented later, had a higher risk of appendiceal perforation, and required a
      longer hospital stay. The parents of these children either failed to recognize
      the significance of their children's symptoms, or delayed seeking medical advice
      because of financial or logistical reasons. The gatekeeper consultation, required
      by the health maintenance organizations (HMO) did not result in a delay in
      presentation or have a negative impact on morbidity. Providing easier access to a
      primary care physician and improving parental health education/awareness may
      shorten the time until presentation for the uninsured/Medicaid patient.

PMID- 8863227
TI  - Appendicitis in children in the managed care era.
AB  - Acute appendicitis is the most common condition requiring emergency operation in
      children. Late appendicitis is still a major source of morbidity and potential
      mortality. It has been suggested that managed care programs are responsible for a
      delay in surgical referral and consequently an increased risk of morbidity and
      mortality. In light of the increasing use of managed care, the authors reviewed
      their experience with pediatric acute appendicitis in managed care and indemnity
      insurance patients. The charts of all pediatric appendectomy patients treated
      between January 1990 and March 1995 were reviewed. Payor status, surgical and
      pathological findings, hospital course, and follow-up findings were documented.
      If the operative note or the pathology report described the appendix as
      gangrenous or perforated, the case was considered to be late appendicitis. Group
      I patients had traditional indemnity insurance; group II patients were in our
      institution's managed care plan. One hundred two patients were identified (28 in
      group 1, 74 in group II). Late appendicits was found less often in the managed
      care group (21.6% v 42.9%; P < .01). This resulted in a lower rate of major
      complications (1.4% v 3.6%) and a lower overall complication rate (2.7% v 7.1%).
      Group II also had a shorter hospital stay (2.6 days v 4.5 days; (P < .01) and
      lower average hospital charges ($6,507 v $8,754 (P < .01). These results do not
      demonstrate any adverse affect on outcome for children with acute appendicitis
      who have a managed care plan. In fact, the incidence of late appendicitis among
      these patients was half of that of the indemnity-insured patients. The lower risk
      of late appendicitis resulted in a shorter length of stay and lower hospital
      charges. These results suggest that managed care programs can provide quality
      care along with a significant reduction in costs; no delay in appropriate
      surgical referral was demonstrated.

PMID- 8863228
TI  - Button device for antegrade enema in the treatment of incontinence and
      constipation.
AB  - Antegrade enema through an appendicostomy is effective in improving the quality
      of life for patients with incontinence or severe constipation. For patients
      without an appendix, a conventional gastrostomy button was used to create a
      cecostomy (or ileostomy) that served as a port for the administration of enema
      solutions.

PMID- 8863229
TI  - Surgical evaluation and management of refractory constipation in older children.
AB  - Chronic constipation is a common childhood problem that accounts for 3% to 5% of
      pediatric visits and 10% to 25% of referrals to pediatric gastroenterologists.
      The etiology of constipation can be elusive, and extensive investigation often
      fails to identify a specific cause. The authors conducted a 5-year retrospective
      review of the patients referred for deep transanal rectal biopsy to determine the
      usefulness of this procedure in the evaluation and subsequent surgical management
      of refractory constipation. Specimens obtained by transanal rectal biopsy
      established a diagnosis for 30 of the 70 patients, and 17 of these 30 had
      subsequent procedures in the treatment of their constipation. The authors
      conclude that transanal rectal biopsy identifies a significant number of patients
      with previously unidentified neuroenteric disorders who may benefit from
      additional surgery in the treatment of constipation refractory to medical
      management.

PMID- 8863230
TI  - Gastroschisis increases small bowel nitric oxide synthase activity.
AB  - In gastroschisis, the eviscerated fetal bowel frequently is damaged and this
      results in hypoperistalsis and malabsorption. The mechanistic link that ties
      gastroschisis-induced intestinal damage to dysfunction may be nitric oxide (NO)
      and the enzyme responsible for producing it, NO synthase. Using a fetal rabbit
      model, the authors investigated the hypothesis that the hypoperistalsis and
      malabsorption associated with gastroschisis may be attributable to abnormal small
      bowel NO synthase activity. Using the 3H-arginine-to-3H-citrulline conversion
      assay, they measured NO synthase activity in the small bowel of full-term fetal
      rabbits with and without gastroschisis. The mean total small bowel NO synthase
      activity of fetal rabbits with gastroschisis was 2.5 times greater than that of
      control littermates without gastroschisis (n = 6; 5,726 +/- 834 v 2,208 +/- 537
      mean pmol/mg protein/min; P = .004). This increased NO synthase activity also was
      studied by measuring the individual isoforms of NO synthase, and the site of
      increased NO synthase activity was localized to the small bowel epithelium and
      neurons. After detecting and localizing the gastroschisis-induced increase in NO
      synthase activity, the authors explored the mechanism of this increase using
      NADPH-diaphorase staining. With this histological staining technique, no
      quantitative increase was found in the small bowel NO synthase of the rabbits
      with gastroschisis. This suggests that the increased NO synthase activity found
      in these rabbits is the result of accelerated enzyme kinetics. These findings
      suggest that the increased NO synthase activity caused by gastroschisis may
      contribute to the common clinical sequelae of malabsorption and intestinal
      dysmotility.

PMID- 8863231
TI  - Trophic effects of interleukin-11 in rats with experimental short bowel syndrome.
AB  - Interleukin-11 (IL-11) is a multifunctional cytokine, derived from bone marrow
      stromal cells, that stimulates proliferation of stem/progenitor precursor cells
      in the small intestinal crypts and accelerates recovery of intestinal mucosa
      after cytoablative therapy. This study evaluates whether IL-11 can improve the
      function and structure of the small intestine and enhance adaptation in an
      experimental model of short bowel syndrome. After 90% small bowel resection, 32
      Sprague-Dawley rats were divided randomly into eight experimental groups of four
      animals each. Four groups were treated with IL-11 (125 micrograms/kg twice daily,
      subcutaneously), and the four control groups were treated with a similar volume
      (0.1%) of bovine serum albumin (BSA). The animals were weighed daily and were
      killed on day 2, 4, 6, or 8; remnant small bowel was evaluated for villus height
      and crypt cell mitosis. The body weight of the animals that received IL-11 was
      significantly greater at the beginning of postoperative day 4 in comparison to
      that of the BSA groups (P < .01 during days 5 to 7). The rats that had IL-11 also
      had significantly greater villus height and crypt cell mitotic rates (P < .05).
      These observations suggest that IL-11 has a trophic effect on the small bowel
      during the adaptive phase that follows massive bowel resection and may be useful
      in the treatment of short bowel syndrome.

PMID- 8863232
TI  - Alpha-1-proteinase inhibitor prolongs small intestinal graft preservation and
      survival.
AB  - Organ preservation solutions currently used for cold storage of human donor
      organs are less effective in preserving small intestinal grafts than other organ
      grafts. The maximal safe period of cold preservation for human small intestinal
      graft is only about 6 hours. The pathology of preserved and reperfused small
      intestinal grafts is characterized by mucosal autolysis and sloughing. The
      authors speculated that the preservation/reperfusion injury results from a
      proteinase/proteinase-inhibitor imbalance in the graft that favors tissue
      degradation. This study evaluates whether the addition of an alpha-1-proteinase
      inhibitor (alpha-1-PI) to the preservation solution can improve graft survival
      after small bowel transplantation. Forty small intestinal grafts (20 cm long)
      were harvested from Lewis rats. The grafts were divided randomly into three
      groups and were preserved in one of the following solutions: normal saline (NS)
      (n = 10), alpha-1-PI (25 mg/mL; n = 20), or proteinase-free bovine serum albumin
      (BSA) (25 mg/mL; n = 10). After 12-hour cold storage in the respective solutions,
      the grafts were transplanted orthotopically into syngeneic recipients. Full
      thickness graft biopsies were performed before and 1 hour after
      revascularization. The effectiveness of preservation was judged by graft
      histopathology and recipient survival. Histological studies showed that there was
      less mucosal autolysis and sloughing of the grafts in the alpha-1-Pl group than
      in the other two groups. All recipients in the NS and BSA groups died of graft
      failure within 7 days (NS: median, 4 days; range, 2 to 5 days; BSA: median, 6
      days; range, 4 to 7). However, 60% (12 of 20) of the recipients in the alpha-1-PI
      group survived more than 90 days (median, > 90 days; range, 4 to > 90 days; P <
      .005 v NS or BSA groups, log-rank method). These data suggest that the inclusion
      of alpha-1-PI in the preservation solution may enhance graft integrity and
      improve the surgical outcome after small bowel transplantation.

PMID- 8863233
TI  - Management of esophageal varices in children by endoscopic variceal ligation.
AB  - Endoscopic variceal sclerotherapy (EVS) has been considered the mainstay of
      therapy for bleeding esophageal varices in adults. However, recent data have
      shown that endoscopic variceal ligation (EVL) is just as efficacious and has
      fewer complications than EVS. Although there are many reports concerning EVL in
      adults, only a few studies have been done in children. This report describes
      experience with EVL in 22 children with esophageal variceal hemorrhage. Eighty
      seven EVL procedures were performed during a 9-year period in 22 children. The
      causes of portal hypertension were biliary atresia (10), portal vein thrombosis
      (8), chronic active hepatitis (1), cirrhosis secondary to cystic fibrosis (2),
      and primary sclerosing cholangitis (1). The age range at the onset of variceal
      bleeding was 8 months to 19 years. Twelve patients had EVS before EVL treatment
      was begun. Distal esophageal varices (one to four per session) were mechanically
      ligated using an elastic band ligature device attached to a flexible endoscope.
      The aim of therapy was obliteration of distal esophageal varices by EVL, every 2
      to 4 weeks, until eradication. Subsequent EVL was dictated by the status of the
      varices. Outcome was assessed with respect to survival, rebleeding, status of
      varices, and complications. The patients underwent a mean of four sessions of EVL
      (range, one to eight). Four patients subsequently underwent liver
      transplantation. Of the 18 patients remaining (average follow-up period, 5.3
      years), 12 had their varices eradicated (average of four EVL sessions), four are
      still in treatment, one has not been evaluated in the past 4 years, and one died
      of liver failure. Complications included bleeding between sessions (6 patients),
      cervical esophageal perforation (1 patient), and transient fever (2 patients). No
      child has experienced symptoms of esophageal stenosis or gastroesophageal reflux.
      Two patients died of liver disease, unrelated to bleeding from portal
      hypertension. EVL is effective in controlling variceal hemorrhage in children
      with portal hypertension, regardless of etiology. The complication rate is low,
      and EVL is an acceptable and perhaps preferable alternative to EVS in children
      with esophageal varices.

PMID- 8863234
TI  - The effect of gestational age at birth on morbidity in patients with
      gastroschisis.
AB  - Infants born with gastroschisis frequently present with an eviscerated intestinal
      segment that is inflamed and thickened. The damaged segment of intestine displays
      absorption and motility disturbances for a variable period of time after
      gastroschisis repair. Clinical and animal research suggests that the damage to
      the eviscerated intestine is caused by prolonged exposure to amniotic fluid
      and/or progressive constriction on the intestine and its blood supply by the
      umbilical ring. Some obstetricians and pediatric surgeons have advocated early
      elective delivery to decrease the exposure of the bowel to these potentially
      damaging influences. Fifty-five patients underwent gastroschisis repair at the
      authors' institution during the last 6 years. Many of these patients had early
      elective delivery after their pulmonary maturity was judged adequate based on
      their amniotic lecithin/sphingomyelin ratios. The patients were divided into
      three groups according to gestational age at the time of delivery. Elective early
      delivery did not lessen the need for silo closure or hasten the time until
      enteral feeding could be tolerated. The hospital stay was not shortened for the
      early delivery group. This retrospective review supports the concept that
      patients with sonographically identified antenatal gastroschisis are best managed
      by delivery at full term.

PMID- 8863235
TI  - Liver hemorrhage during laparotomy in patients with necrotizing enterocolitis.
AB  - Major liver hemorrhage (LH) without obvious iatrogenic injury was recently
      observed in several patients during operation for necrotizing enterocolitis
      (NEC). The purpose of this study was to determine the incidence and risk factors
      associated with the development of LH in patients with NEC. METHODS: The hospital
      charts of patients with NEC who underwent surgical exploration during a 5-year
      period (1989-1994) were reviewed. The patients in whom LH developed without
      obvious significant iatrogenic liver injury were compared with those who did not
      have LH. RESULTS: Eight of the 68 patients reviewed had LH. The survival rate for
      those with LH was 13%, compared with 88% for those without LH (P < .001). The
      patients with LH had a younger gestational age (28 +/- 3 weeks v 32 +/- 5 weeks)
      and a lower birth weight (1,262 +/- 489 g v 1,649 +/- 666 g); however, the
      differences were not significant. The patients with LH had significantly lower
      preoperative mean arterial blood pressure (35 +/- 1 mm Hg v 46 +/- 3 mm Hg; P <
      .001) and required greater fluid intake (272 +/- 28 mL/kg/d v 186 +/- 9 mL/kg/d;
      P < .01) for the 24 hours preceding surgery. CONCLUSION: LH is as an important
      and lethal complication associated with laparotomy in very small infants with
      NEC. The presence of hypotension and the administration of large amounts of
      volume in the preoperative period appear to be risk factors. Earlier surgical
      intervention and restoration of blood pressure using inotropic agents, once a
      particular level of fluid administration has been achieved, my be preventive.

PMID- 8863236
TI  - Neonatal lipid utilization increases with injury severity: recombinant human
      growth hormone versus placebo.
AB  - Increased lipid oxidation has been observed in injured adult and pediatric
      patients who receive growth hormone (GH). In infants, whose bodies make fat more
      readily (de novo lipogenesis), this effect has not been tested. After surgery for
      necrotizing enterocolitis or gastroschisis, 22 neonates (average gestational age,
      35 weeks; average postnatal age, 7 days) were provided basal protein-calorie
      parenteral repletion, and were prospectively randomized to receive either
      recombinant human GH (rhGH, 0.2 mg/kg/d) or placebo for 6 days. Injury severity
      was established by serial serum C-reactive protein (CRP) levels (high v low
      stress: CRP > or = 6.0 mg/dL v < 6.0 mg/dL). Indirect calorimetry was used to
      measure energy expenditure (MEE), respiratory quotient (RQ), net lipid oxidation
      (Fe), and lipid oxidative O2 consumption (VO2f). Among the GH+ group, MEE, Fe,
      and VO2f were significantly higher for the high-stress patients (MEE: 52.87 +/-
      13.35 v 42.57 +/- 9.47 kcal/kg/d; P < .03: Fe; 18.32 +/- 27.74 v 0.81 +/- 13.47
      kcal/kg/d; P < .02; VO2f: 7.21 +/- 9.86 v 0.01 +/- 7.42 L/d, P < .02), and RQnp
      was significantly lower in the high-stress patients (RQnp: 0.93 +/- 0.14 v 1.05
      +/- 0.11; P < .02). In addition, Fe and RQnp were directly proportional to
      carbohydrate intake (CHO) in the high-stress patients (CHO to Fe: Pearson r = 
      .701; CHO to RQnp: Pearson r = .714; P < .05). Lipid oxidation was directly
      proportional to stress severity, was higher in the GH group (18.32 v 11.91
      kcal/kg/d for the placebo group), and was depressed in response to increased CHO
      intake in all groups. Lipid is an important energy source in acutely injured,
      especially severely stressed neonates. Lipid substrate utilization is improved
      with GH supplementation during acute metabolic stress. In addition, excess
      carbohydrate delivery reduces the amount of lipid utilized for energy metabolism.
      An appropriately balanced, mixed-fuel formula should be used for caloric
      repletion in this infant population.

PMID- 8863237
TI  - Endodermal sinus tumor in children.
AB  - Malignant germ cell tumors account for about 3% of neoplasms in children, and
      endodermal sinus tumor (EST) is the most common histological subtype. The authors
      reviewed 22 years' experience (at their institution) in the management of 37
      patients with this tumor. Fifteen of them (41%) had a sacrococcygeal primary, 10
      had a testicular tumor (27%), 6 had an ovarian tumor (16%), 3 had a vaginal tumor
      (8%) and 3 had tumors at other sites (8%). Seven (19%) patients presented with
      metastatic disease, primarily pulmonary. The serum alpha-fetoprotein (AFP) level
      was elevated in all cases tested. The initial chemotherapy regimen included
      vincristine, actinomycin, cyclophosphamide (VAC), and Adriamycin (6 patients),
      but since 1985 the regimen has been changed to include cisplatin or Carboplatin,
      etoposide, and bleomycin (21 patients). Eight patients with testicular tumors
      initially were treated with surgical excision alone. Computed tomography results
      were a poor predictor of recurrence, but AFP surveillance was extremely
      sensitive. No second-look operation detected residual tumor in the absence of AFP
      elevation. Initial relapse for all patients tended to occur early (within 2
      years), locally, and often with pulmonary metastases. Although historically the
      prognosis for patients with EST has been poor, the overall 2-year survival rate
      in this series was 70%. The best prognosis was among the children who had a
      testicular primary tumor (survival rate, 100%). The 2-year survival rate for
      patients with ovarian tumors was 67%; for those with sacrococcygeal primaries it
      was 60%. These results suggest that the prognosis for children with EST has
      improved significantly over the past decade. Contributing factors include therapy
      based on cisplatin, etoposide, and bleomycin, and relapse surveillance with
      serial AFP determinations. Second-look procedures should be reserved for patients
      who have an increasing level of serum AFP, suspicious computed tomography
      findings, and no obvious evidence of metastatic disease.

PMID- 8863238
TI  - Malignant fibrous histiocytoma in children.
AB  - Because malignant fibrous histiocytoma (MFH) rarely occurs in children, the
      natural history of this tumor and prognostic factors predictive of outcome have
      not been well described. The charts of all pediatric patients with MFH seen at
      M.D. Anderson Cancer Center were reviewed with respect presentation, treatment,
      and outcome, in an attempt to determine prognostic factors that are predictive of
      survival. Forty-four pediatric patients were identified. Extremities were the
      most common tumor site (31 of 44 patients). Five patients presented with
      angiomatoid histology subtype; all subsequently survived. The estimated 5-year
      survival rate was 85% for clinical group I patients, 87% for clinical group II,
      53% for clinical group III, and 0% for clinical group IV. The estimated 5-year
      survival rate was 95% for patients with tumors of less than 5 cm in diameter and
      45% for those with larger tumors. Overall, the estimated 5-year survival rate was
      71%. Significant prognostic factors found to affect survival (by univariate
      analysis) were clinical group, tumor size, and recurrence. Gender and race were
      not significant predictors. The use of chemotherapy and radiation was not found
      to improve the chance of survival, but this most likely reflected the more
      frequent use of adjuvant therapy in patients with unresectable or high-grade
      tumors. Although adequate surgical resection continues to be the most effective
      treatment, investigation of adjuvant chemotherapy and radiation therapy on
      protocol is warranted.

PMID- 8863239
TI  - The argument for conservative, delayed surgery in the management of prostatic
      rhabdomyosarcoma.
AB  - Exenteration is no longer required for most patients who have rhabdomyosarcoma
      (RMS) of the prostate. This site comprised only about 5% of newly diagnosed cases
      in the IRS-III (1984-1991). The mean age at the time of diagnosis was 5.3 yrs
      (range, 0 to 19 years). Most tumors were relatively large, had embryonal
      histology, and were clinically localized but unresectable without major loss of
      organ function. The 44 patients with group III tumors (gross residual disease)
      were treated according to the IRS-III protocol. Forty-three of them underwent
      biopsy only, and one patient had subtotal resection as the initial procedure. The
      average number of surgical procedures per patient was two (range, one to five).
      Six of the 44 patients had no additional surgery. The second-look procedures
      performed in the other 38 patients included exenteration (14), prostatectomy (7),
      cystoscopic/perineal needle biopsy (8), laparotomy with biopsy (6), and subtotal
      excision with bladder salvage (3). Additional surgery was required for four
      patients, for evaluation of a residual mass, postoperative fistula, ureteral
      stricture, or small bowel obstruction. Six patients with relapse or residual
      disease underwent additional chemotherapy and late exenteration (3),
      prostatectomy (1), or biopsy (2). Four of the six have been cured, one is in
      treatment for a second malignancy, and the other has residual disease after
      exenteration. Thirty-six of the 44 patients with group III tumors have been cured
      (minimum follow-up period, 6 years; range, 6 to 11 years), compared with 23 of
      the 47 in IRS-II (1978-1984) (P = .001). Two of the six deaths in this group were
      caused by infection. The bladder salvage rate for those cured of their disease
      also was better (64% v 57% for IRS-II). The two patients with group IIA tumors
      were cured by gross primary excision, local radiotherapy, and vincristine and
      actinomycin therapy. By contrast, all patients with metastatic disease (group IV)
      died of the tumor. Conservative, delayed surgery, performed after intensive
      chemotherapy with or without radiotherapy, yields a better cure rate while
      maintaining a high rate of bladder salvage in children with group III prostatic
      RMS.

PMID- 8863240
TI  - Respiratory insufficiency at birth: a predictor of mortality for infants with
      omphalocele.
AB  - For infants with omphalocele, the size of the defect and the presence of
      associated anomalies are well known prognostic factors. However, the prognostic
      importance of the respiratory status at birth has not been well defined. The
      authors reviewed the records of 30 infants with omphalocele (treated during a 10
      year period) to determine whether respiratory insufficiency at birth affected
      survival. Eighteen infants did not require ventilatory support before repair of
      the omphalocele. The mean gestational age and birth weight were 38.2 +/- 2.6
      weeks and 3.4 +/- 0.6 kg, respectively. Cardiac or other major associated
      anomalies were present in six infants (33%). Seven (39%) had a "giant"
      omphalocele (ie, liver-containing and/or omphalocele sac > 5 cm in diameter). The
      average length of ventilatory support was 3.2 days. All infants in this group
      were managed by primary (14) or staged closure of the omphalocele (4) immediately
      after birth. One infant died, but the remainder survived without any significant
      complications. Twelve infants had severe respiratory distress at birth and
      required positive pressure ventilation (mean peak inspiratory pressure, 31.4 +/-
      1.2 cm H2O; mean FiO2, 0.8 +/- 0.1). The mean gestational age and birth weight
      were 32.7 +/- 3.5 weeks and 1.9 +/- 0.8 kg, respectively. Cardiac or other major
      associated anomalies were present in nine infants (75%), and eight (67%) had a
      giant omphalocele. The average length of ventilatory support was 57.7 days, which
      was significantly longer than for the previous group (P < 0.001). Two infants
      died of respiratory failure within 48 hours of birth, before the initiation of
      any treatment for the omphalocele. Six were managed with surgical repair of the
      omphalocele, primary or staged, immediately after birth. In four, topical
      treatment was used to allow improvement in the respiratory status. Only one of
      the six infants initially managed by surgical repair survived, whereas three of
      the four infants managed nonsurgically recovered. Stepwise logistic regression
      analysis showed that the presence of respiratory distress at birth was the only
      significant predictor of mortality, independent of gender, gestational age, birth
      weight, presence of other anomalies, or size of the omphalocele (odds ratio =
      25.48; likelihood ratio test = 13.86; P < .001). In conclusion, respiratory
      failure at birth in infants with omphalocele is a significant predictor of
      mortality. Initial conservative management of the omphalocele until there is
      improvement in the respiratory status may result in a better outcome.

PMID- 8863241
TI  - Maximal oxygen consumption and stress performance in children operated on for
      congenital diaphragmatic hernia.
AB  - The long-term follow-up of patients operated on for congenital diaphragmatic
      hernia (CDH) at birth has been extensively evaluated, both clinically and with
      respect to respiratory function. However, little is known about the sports
      practice and stress performance of these subjects. Fifteen of 107 patients
      operated on for CDH underwent exercise stress testing with a stepwise increase in
      workload. A questionnaire was provided, which requested information on sports
      practice and lifestyle. Maximal oxygen consumption [Vo2 max] was measured along
      with dynamic lung volumes. Clinical examination included a whole-body assessment
      (height, weight, skinfolds) and vital parameters (heart rate and blood pressure).
      Fifteen healthy children who practiced regular physical activity (2 to 4
      hours/week) served as controls. All the CDH patients experienced a good
      lifestyle, but only 8 of them were participating in sports. Exercise duration and
      Vo2 max were significantly lower for the CDH patients, and were lowest for the
      sedentary patients. Therefore, the reduced Vo2 max of these otherwise healthy
      children most likely represents a lower degree of physical fitness rather than
      decreased respiratory function. Fitness is an expression of well-being; thus,
      there is evidence that these patients could safely participate in competitive
      motor activities.

PMID- 8863242
TI  - Long-term pulmonary sequelae in survivors of congenital diaphragmatic defects.
AB  - Between 1948 and 1980, 107 of 164 patients survived after repair of a congenital
      diaphragmatic defect. Sixty of the survivors (mean age, 29.6 years; SD, 9.0
      years) underwent clinical examination, chest radiography, spirometry, and
      diffusing capacity measurement 11 to 41 years after the diaphragmatic repair.
      Twenty-seven of the 60 had body plethysmography, xenon 133 radiospirometry, and a
      test of bronchial hyperreactivity. Subjective physical performance was below
      average for eight patients (13%), seven patients (12%) had asthma, and four
      patients (7%) reported increased susceptibility to respiratory infections. Thirty
      one patients (52%) had ventilatory impairment, which was obstructive in nine
      (15%), restrictive in seven (12%), and obstructive and restrictive in 15 patients
      (25%). Nine (35%) of the 26 patients tested had bronchial hyperreactivity. The
      presence of ventilatory impairment and bronchial hyperreactivity correlated with
      the initial clinical severity of the affliction. Chest asymmetry (29 patients;
      48%) and scoliosis (16 patients; 27%) were more common among patients with
      ventilatory impairment than among those with normal spirometric findings.
      Ventilatory impairment and thoracic deformities are common in adults with
      repaired diaphragmatic defects. Surveillance should begin in infancy and continue
      into adulthood.

PMID- 8863243
TI  - Fetal endoscopic ('Fetendo') tracheal clip.
AB  - Fetal surgery can correct several life-threatening malformations before birth.
      Despite recent advances in fetal surgery, preterm labor remains a major problem
      directly related to the large uterine incision required for fetal exposure. Fetal
      endoscopic surgery ("Fetendo") obviates the need for a large uterine incision and
      may reduce the overall risks of fetal surgery by causing less uterine trauma and
      ultimately less preterm labor. Temporary tracheal occlusion is a promising
      strategy to enlarge the lungs in fetuses with congenital diaphragmatic hernia.
      Using the technology developed for laparoscopic surgery and for temporary
      tracheal occlusion, we have developed an endoscopic technique for tracheal
      occlusion with an endoscopic clip in a fetal sheep model. The evolution of this
      technique may allow temporary tracheal occlusion without incisional hysterotomy
      or maternal laparotomy.

PMID- 8863244
TI  - Surfactant rescue in the fetal lamb model of congenital diaphragmatic hernia.
AB  - Surfactant therapy given before the onset of ventilation (surfactant prophylaxis)
      has been shown to improve oxygenation, ventilation, and pulmonary hemodynamics in
      the lamb model of congenital diaphragmatic hernia (CDH). The aim of this study
      was to assess the efficacy of surfactant administered after the onset of
      ventilation ("surfactant rescue"). Ten lambs with surgically created CDH were
      instrumented, at full term, to measure pulmonary blood flow and pulmonary
      vascular resistance (PVR). Catheters also were positioned for monitoring of
      systemic blood pressure and arterial blood gases. The animals were delivered and
      pressure-ventilated according to a standard protocol (PIP, 30 cm; PEEP, 4 cm;
      respiratory rate, 60 breaths per minute). After 30 minutes of ventilation, five
      animals received an intratracheal dose of calf lung surfactant extract (50
      mg/kg). The animals were studied for 4 hours. Surfactant rescue had no
      discernible effect on Pco2, Pco2, or pH. There was an increase in pulmonary blood
      flow, but it was not significant. The dramatic improvement in oxygenation,
      ventilation, and pulmonary blood flow found with prophylactic surfactant cannot
      be reproduced when surfactant is administered as rescue therapy. This indicates
      that the surfactant is not being delivered adequately, the lungs have already
      incurred significant barotrauma, and/or the surfactant is being inactivated by
      alveolar protein. Therefore, the authors suggest that when exogenous surfactant
      therapy is being considered for the fetus or newborn with CDH, it should be
      administered as early as possible, preferably before the infant's first breath.
      Prenatal diagnosis and delivery in a tertiary care center would facilitate this
      optimum management.

PMID- 8863245
TI  - The effect of pre-ECLS ventilation time on survival and respiratory morbidity in
      the neonatal population.
AB  - Although mechanical ventilation for more than 7 to 10 days has been considered a
      contraindication to the application of extracorporeal life support (ECLS) in
      neonates, the outcome and respiratory morbidity for newborns placed on ECLS after
      more than 7 days of ventilation have not been well characterized. The purpose of
      this study was to determine the impact of pre-ECLS ventilation time on the rate
      of survival, the likelihood of the development of bronchopulmonary dysplasia
      (BPD), and the need for supplemental oxygen at the time of discharge. Examination
      of the Extracorporeal Life Support Organization (ELSO) Registry showed that 6,110
      neonates were treated for respiratory failure with a pre-ECLS ventilation time of
      less than 14 days between January 1990 and May 1995. Gestational age (GA), birth
      weight (BW), indication for ECLS, and diagnosis were compared with the rate of
      survival, the discharge diagnosis of BPD, and the need for home oxygen. The GA
      and BW of neonates placed on ECLS during the first week of life (n = 5,888) did
      not differ significantly from those of neonates whose ECLS was begun in the
      second week of life (n = 222). The neonates were divided into two groups (early,
      ventilation time of 3 to 6 days; late, ventilation time of 7 to 10 days) to
      determine the odds ratios for survival, BPD, and home oxygen. Logistic regression
      analysis was used to develop a model to predict the rate of survival, the risk
      for the development of BPD, and the need for home oxygen given the length of pre
      ECLS ventilation time. The late group was less likely to survive (odds ratio,
      1.8; 95% confidence interval [CI], 1.21 to 2.68). The late group also had
      approximately twice the risk for the development of BPD (odds ratio, 1.9; 95% CI,
      1.2 to 3.04) and a trend toward an increased incidence of home oxygen use (odds
      ratio, 1.55; 95% CI, 0.92 to 2.60). The authors conclude that (1) there is a
      greater risk of mortality and BPD and a trend toward an increased need for home
      oxygen with increased time on the ventilator before ECLS; (2) at 14 days the
      predicted probability of survival is still 53% (95% CI, 31% to 74%); (3) at 14
      days the predicted probability of BPD is 54% (95% CI, 28% to 78%); and (4) based
      on these data, it is reasonable to consider application of ECLS to patients who
      have had mechanical ventilation for up to 14 days.

PMID- 8863246
TI  - ECMO in evolution: the impact of changing patient demographics and alternative
      therapies on ECMO.
AB  - The incidence of neonatal extracorporeal membrane oxygenation (ECMO) is
      decreasing nationally. This decrease is presumed to be a result of the emergence
      of alternative technologies such as high-frequency oscillatory ventilation
      (HFOV), nitric oxide (NO), and surfactant therapy as well as others. The purposes
      of the present report were to determine just how rapidly the demographics of ECMO
      are changing and to determine the impact of competing technologies on ECMO use.
      The authors reviewed their entire ECMO experience of 455 cases (370 neonatal, 38
      pediatric, and 47 cardiac). The neonatal cases also were separated into
      diagnostic groups: MAS (meconium aspiration syndrome), PPHN (persistent pulmonary
      hypertension of the newborn), RDS (respiratory distress syndrome), and sepsis. To
      allow statistical comparison, the patients were divided into four chronological
      groups, of equal 3-year duration, spanning the 12 years that ECMO has been
      available. The results of the analysis demonstrated four principle findings. (1)
      The total number of patients receiving ECMO per year was declining (P = .0001).
      This decline was attributable to a reduction in the total number of neonatal
      patients, with the exception of cases of congenital diaphragmatic hernia. (2) The
      complexity of each ECMO run was increasing, as evidenced by substantial increases
      in mean ECMO duration per patient and an increase in the incidence of patient
      complications on ECMO (P = .0001). (3) There has been a significant decrease in
      the overall survival rate for patients treated with ECMO (P = .0001). (4) The
      ECMO population mix has shifted away from straightforward neonatal cases and
      toward the more complex pediatric and cardiac cases. This demographic shift has
      occurred as a result of improvements in pre-ECMO management of neonatal patients,
      and is primarily responsible for the findings noted above. However, there also
      has been a worsening of condition severity within each diagnostic group, which
      also is partly responsible for the changes noted. If these trends continue,
      pediatric, cardiac, and CDH patients will likely account for the majority of ECMO
      patients. Consequently, existing ECMO centers must be prepared to adapt to the
      changing demographics by evolving programs that support pediatric, cardiac, and
      adult patients, in addition to neonates. Furthermore, the complexity associated
      with transporting these unstable older patients and the likelihood that the
      number of active ECMO centers will decline may require remaining ECMO centers to
      develop long-distance ECMO transport capabilities.

PMID- 8863247
TI  - The effects of venous occlusion on cerebral blood flow characteristics during
      ECMO.
AB  - Extracorporeal membrane oxygenation (ECMO) in the newborn usually requires
      occlusion of a jugular vein, and frequently a carotid artery. The acute effects
      of jugular vein occlusion on cerebral blood flow characteristics have received
      little investigation. Six newborns (age range, 0 to 5 days; weight, 2.4 to 3.1
      kg) were treated with venoarterial ECMO, with additional placement of a cephalic
      venous catheter, for meconium aspiration (4) or persistent fetal circulation (2).
      Doppler duplex ultrasound evaluation of blood flow velocity and resistive index
      (RI) in the right (RMCA) and left (LMCA) middle cerebral arteries was performed
      just before ECMO, immediately after ECMO onset, and at 8,24, and 48 hours of
      ECMO. Arterial Po2 was maintained at 80 to 120 mm Hg. Pco2 at 35 to 45 mm Hg. and
      mean arterial pressure at 50 to 60 mm Hg. Flow velocity was measured with the
      cephalic venous catheter both open and closed. Closure of the cephalic venous
      cannula resulted in an abrupt, significant reduction in RMCA flow velocity and a
      significant increase in RI at the onset of ECMO and at 8 hours of ECMO. Opening
      the cannula restored the velocity and RI to normal. LMCA velocity and RI did not
      change with closure of the cephalic venous cannula. All infants survived ECMO,
      and five of the six are normal neurologically at 1 year of age. These data show
      that right carotid ligation alone did not change cerebral arterial blood flow
      velocity, but the addition of venous occlusion significantly decreased RMCA flow
      velocity, which was alleviated by cephalic venous drainage. After 24 hours of
      ECMO, this effect disappeared. This suggests that cephalic venous drainage may
      help prevent the neurological complications of ECMO by maintaining normal
      cerebral blood flow.

PMID- 8863248
TI  - Type IV laryngotracheoesophageal clefts: surgical management for long-term
      survival.
AB  - Complete laryngotracheoesophageal clefts (types III and IV) are rare congenital
      anomalies that occur when the primitive foregut fails to separate into the
      tracheobronchial tree and the esophagus. This article summarizes a 10-year
      institutional experience with six infants who had type IV clefts, presents a
      modification of the authors' surgical approach, and identifies pitfalls in the
      management of these infants. Three of the six children are long-term survivors.
      The recognition of specific complicating issues leads to a standardized approach,
      which can result in successful repair and long-term survival.

PMID- 8863249
TI  - Is surgical ligation of a patent ductus arteriosus the preferred initial approach
      for the neonate with extremely low birth weight?
AB  - The optimal approach to a patent ductus arteriosus (PDA) in an extremely low
      birth weight (ELBW) neonate, whether initial surgical ligation or a trial of
      indomethacin, has not been established. The authors reviewed the records of 82
      ELBW premature infants who had surgical ligation of a PDA during a 2-year period.
      Thirty-one received indomethacin before ligation. Bronchopulmonary dysplasia
      (BPD) occurred in 33% of the infants. Predictors of BPD were prolonged positive
      pressure ventilation, severe intraventricular hemorrhage (IVH) and lower birth
      weight (BW). Seventy-seven percent of the infants survived. Predictors of
      mortality were severe IVH, lower BW, and the occurrence of necrotizing
      enterocolitis (NEC). The indomethacin-treated infants had a lower incidence of
      NEC and IVH. Overall, 16% of the patients had perioperative morbidity, and 10% of
      the patients died. The study shows that a trial of indomethacin therapy is not
      associated with increased complications in ELBW infants with PDA.

PMID- 8863250
TI  - Surgical implications of necrotizing fasciitis in children with chickenpox.
AB  - Varicella (chickenpox) affects approximately 90,000 children each year. Although
      most cases resolve, some develop necrotizing soft tissue infections secondary to
      group A streptococcus and staphylococcus. Delay in diagnosis is common. At the
      time of initial presentation, the need for surgical intervention is not always
      clear. The authors conducted a retrospective review of 30 patients with varicella
      (seen from December 1993 to June 1995) for whom there was clinical concern for
      necrotizing soft tissue infection. Various parameters were examined, including
      tachycardia, band count, temperature, and clinical symptoms, to differentiate the
      children who required surgery from those who did not. Of the 30, 22 underwent
      surgery. Eighteen had necrotizing fasciitis and required debridement, and four
      had abscesses that were incised and drained. Eight patients had simple cellulitis
      and did not require operation. Group A streptococcus was the most common organism
      cultured. All patients were treated with appropriate antibiotics. Twenty of the
      22 surgical patients had elevated band count (> or = 5%), 21 had tachycardia, and
      18 were febrile at the time of presentation (> 4 days after the onset of
      chickenpox). Although all patients with necrotizing fasciitis had tachycardia,
      this sign was a less specific indicator for surgery than was increased band
      count. Severe pain, erythemia, and induration was the most common signs/symptoms
      in the surgical patients. The survival rate for these 30 patients was 100%, and
      there was little long-term morbidity. The authors recommend immediate surgical
      intervention for children with chickenpox who present more than 2 or 3 days after
      the onset of the viral illness with symptoms that include fever, tachycardia, and
      an elevated band count in association with an erythematous, indurated, painful
      lesion. With this sign/symptom complex, the presumptive diagnosis must be
      necrotizing fasciitis until proven otherwise. If the patient has suspicious
      symptoms or if these symptoms are associated with tachycardia or an elevated band
      count, the patient warrants admission, institution of intravenous fluids,
      nafcillin, clindamycin, and close observation over several hours. If the symptoms
      progress over the next few hours or if the tachycardia persists despite
      rehydration and antibiotics, the patient should be taken to the operating room
      for exploration. The authors strongly endorse such exploration despite the risk
      of a negative operation, because the morbidity and mortality associated with
      delayed surgical treatment are potentially significant. With prompt aggressive
      surgical and medical treatment, a good outcome can be anticipated for these
      patients.

PMID- 8863251
TI  - Necrotizing fasciitis in children: prompt recognition and aggressive therapy
      improve survival.
AB  - Necrotizing fasciitis (NF) is a bacterial infection of the soft tissues with a
      fulminant course and a high mortality rate. The authors performed a review to
      define the diagnosis, bacteriology, and management of NF in the pediatric
      population. This report of 20 cases treated over 18 years represents the largest
      reported pediatric experience. These infections were attributable to secondary
      infection of varicella lesions (5), omphalitis (4), extremity lesions (4),
      perineal infections (3), head and neck lesions (2), inguinal herniorrhapy (1),
      and breast abscess (1). Nineteen of the 20 children were healthy, without chronic
      disease or immunosuppression. All patients presented with an altered sensorium
      and signs of systemic toxicity. Fever (40%), tachycardia (70%), and abnormal
      white blood cell count (50%) were not uniformly present. There was marked tissue
      edema in all patients, with a characteristic peau d'orange appearance in 18.
      Seven infections were caused by streptococcus; the remainder were polymicrobial,
      involving multiple aerobes and anaerobes. Initial gram stain was of limited
      utility; in 14 of 19 cases the result was negative or showed only one of many
      organisms present. Fifteen patients survived and five died. All survivors
      underwent aggressive surgical debridement within 3 hours of admission. The
      survivors required of a mean of 3.8 operations. Fascial excision of up to 35% of
      total body surface area was required. One patient required amputation, two had
      colostomies, and six required extensive skin grafting for reconstruction. All
      five patients who died had delayed initial management. CONCLUSION: NF is a
      serious cause of death in previously healthy children. The diagnosis should be
      considered in the presence of any soft tissue infection presenting with signs of
      toxicity and marked wound edema, even in the absence of fever or abnormal white
      blood cell count. Immediate surgical debridement and coverage with penicillin, an
      aminoglycoside, and metronidazole are essential. Subsequent changes in
      antibiotics should be based on culture data because gram stain results are not
      reliable. More than one operation is required in almost all cases.

PMID- 8863252
TI  - Neutrophil activation and chemotaxis after in vitro treatment with
      perfluorocarbon.
AB  - The in vitro effects of perfluorocarbon (PFC) on human neutrophil activation and
      chemotaxis were examined. Neutrophils were incubated, with and without PFC, and
      were analyzed for chemotaxis through 5-microns and 8-microns pore filters.
      Neutrophil activation was quantitated by flow cytometry. Activation studies
      showed that PFC-treated neutrophil samples (n = 6) produced only 39.83% +/- 25.9%
      (mean +/- SD) of matched control (n = 6) fluorescence. Chemotaxis studies showed
      that PFC-treated neutrophil samples (n = 8) had migration of only 18.63% +/- 6.5%
      (of control values) of neutrophils to the outer boundary of the 5-microns filters
      (n = 8 controls). The 8-microns pore filter migration (n = 8) was similarly low,
      with a mean outer boundary migration count of only 26% +/- 19.8% of the control
      (n = 8) value. Thus, neutrophils exposed to perfluorocarbon produce significantly
      less detectable H2O2 (P < .001) and have a significantly lower chemotactic
      response (P < .001).

PMID- 8863253
TI  - Immediate reconstruction for penile agenesis.
AB  - The goal of treatment for penile agenesis is early female gender assignment and
      feminizing reconstruction of the perineum. Historically, this required multiple
      operations including both vesicostomy and colostomy. The present case
      demonstrates the feasibility of early total reconstruction through a posterior
      sagittal approach that avoids diversion of stool and urine.

PMID- 8863254
TI  - Laparoscopic Swenson pull-through: a comparison with the open procedure.
AB  - This study was performed to compare the standard open Swenson pull-through (OSP)
      with the laparoscopic Swenson pull-through (LSP) for Hirschsprung's disease. The
      Swenson pull-through was performed on eight patients with a rectosigmoid
      transition zone, during a 14-month period, using one camera port and three
      working ports. The results were compared with those of 10 patients with a similar
      lesion treated by the open procedure during an overlapping 19-month period. One
      laparoscopic procedure was converted to the open version because of technical
      difficulties. Both methods had a hand-sewn anastomosis approximately 1 cm above
      the pectinate line. The preoperative variables of age, weight, incidence of
      colostomy, and incidence of Down's syndrome were similar for the two groups. The
      operating time for LSP was similar to that for OSP (4 hours 42 minutes v 4 hours
      37 minutes, respectively: P = NS). Postoperatively, the laparoscopic group had a
      shorter hospital stay (5.25 v 8.8 days; P < .05) and had a shorter period until
      the start of oral intake (2.75 v 5 days; P < .05). The requirement for narcotic
      pain medication was similar (12.6 v 12.8 doses; P = NS). Early postoperative
      complications were more common in the open group (3 wound infections, 1 prolonged
      ileus, and 1 anastomotic leak). No complications occurred in the laparoscopic
      group. Late postoperative follow-up was too short to compare functional results.
      The authors conclude that the Swenson pull-through can be performed safely with
      the laparoscope, with reduced morbidity.

PMID- 8863255
TI  - Laparoscopy for diagnosis and treatment of recurrent abdominal pain in children.
AB  - Extensive radiographic evaluation of children with recurrent abdominal pain (RAP)
      is rarely diagnostic or cost-effective. The authors sought to define the role of
      laparoscopy in the evaluation of children with RAP. Fifteen children underwent
      laparoscopy for RAP in a 2-year period. Their mean age was 12 years (range, 6 to
      16 years), 13 (87%) were female, and the mean duration of symptoms was 11 months
      (range, 2 to 60 months). Thirty-eight imaging studies (excluding plain films) had
      been obtained before laparoscopy, including 19 abdominal sonograms, 9 upper
      gastrointestinal series, four abdominal computed tomography scans, 3 barium
      enemas, 2 isotope scans, and 1 magnetic resonance examination of the head. Only
      two (5%) of these studies provided an accurate diagnosis. Eleven of the 15
      children (73%) had positive findings diagnosed and treated laparoscopically.
      These included eight appendiceal abnormalities (in six patients), three Meckel's
      diverticula, one inguinal hernia, one urachal cyst, one para-fallopian tube cyst,
      and one adhesion to an appendectomy stump. Eight of 11 (73%) children with
      positive findings had immediate resolution of symptoms after laparoscopic
      treatment. Three children with pathological findings at the time of laparoscopy
      had persistent symptoms, which resolved completely within 4 months of the
      laparoscopy. Laparoscopy is an accurate technique for the evaluation and
      treatment of children with RAP. Its early application could provide economic
      benefit by eliminating many low-yield imaging studies and minimizing lost time
      from school.

PMID- 8863256
TI  - Complications of minimal-access surgery in children.
AB  - Minimal-access surgery (MAS) is rapidly becoming the surgical approach of choice
      for a variety of surgical disorders in adults, but its use in children remains a
      relative novelty. Most pediatric surgeons continue to harbor justifiable concerns
      about the morbidity of this modality owing to the cumbersome nature of the
      instruments and the technical difficulty associated with two-dimensional views.
      The purpose of this study was to determine the complication rate and the lessons
      learned from the use of MAS in performing a variety of procedures in a large
      series of children. To determine complications, the authors reviewed the medical
      records of all children (n = 636; age range, 1 month to 19 years) who underwent
      laparoscopy (LAP) or thoracoscopy (THO) during a 5-year period (January 1, 1990
      through December 31, 1994). The follow-up ranged from 1 week to 45 months. THO
      was performed in 62 children. Conversion to thoracotomy occurred in eight
      children (13%), because of inability to localize the lesion (3), unresectibility
      (2), inadequate tissue sample (1), unsafe access (1), hypoxemia (1), or
      inadvertent esophagotomy (1). Postoperatively, two ventilator-dependent children
      had tension pneumothorax after lung resection and required chest tubes. LAP was
      performed on 574 children, with conversion to laparotomy occurring in 15 (2.6%),
      because of technical reasons (10) or intraoperative complications (5). The
      complication rate of LAP was 2% (12 of 574). Early in the experience,
      intraoperative complications that led to laparotomy included hemorrhage during
      appendectomy (2), cholecystectomy (1), and splenectomy (1); and esophagotomy
      during a fundoplication (1). Other technical problems in the postoperative period
      were a malpositioned Nissen fundoplication and a gastric volvulus after
      gastrostomy and Nissen fundoplication owing to improper gastrostomy tube
      position. In addition, two children had a hernia at the umbilical trocar site
      that had been used for contralateral inguinal exploration, and cellulitis
      developed in three patients when a gastrostomy tube was brought out through a
      trocar site. Other complications not specific to MAS included pelvic abscess
      after appendectomy (5); small bowel obstruction after jejunostomy catheter
      placement (1) and combined cholecystectomy/appendectomy (1); enterocolitis (1)
      and severe hyponatremia (1) after pull-through for Hirschsprung's disease; and
      pneumonia after splenectomy (1). The overall complication rate of MAS was 4% (26
      of 626), and there were no deaths. The initial use of MAS was associated with
      technical errors, which decreased with experience. Based on this study, the
      authors recommend (1) routine placement of a thoracostomy tube in children after
      THO if they require postoperative ventilator support; (2) using the open hernia
      sac to place a 70 degrees telescope for contralateral inguinal exploration; and
      (3) not using a trocar site for gastrostomy tube placement in immune-suppressed
      patients. With appropriate training and experience, MAS can be used safely in
      children, for a wide variety of diseases, with minimal morbidity and mortality.

PMID- 8863257
TI  - Hernia survey of the Section on Surgery of the American Academy of Pediatrics.
AB  - The members of the Section on Surgery of the American Academy of Pediatrics were
      surveyed to determine the practice of North American pediatric surgeons in
      infants with inguinal hernia (IH). Case-scenario multiple-choice-design
      questionnaires regarding hernias and hydroceles were sent to all members of the
      Surgical Section, and responses were received from 292 (50%). In healthy full
      term infant boys with asymptomatic reducible IH, 82% of responders perform repair
      electively, no matter what the age or weight. In full-term girls with a reducible
      ovary, 59% perform surgery at the next available time; if the ovary is
      nonreducible but asymptomatic, 44% operate emergently or urgently and 42% at the
      next elective slot. In former preemies, the pattern of repair is as follows. (1)
      For those recently discharged after 2 months in the neonatal intensive care unit
      (NICU) with reducible IH, 65% perform the repair when convenient. (2) A general
      anesthetic is used in 70%; 15% use spinal anesthesia, and 11% use caudal block
      with sedation. (3) If the repair is done in the hospital outpatient (same-day)
      unit, 36% wait until 50 weeks postconception (PC) and 33% wait until 60 weeks PC.
      (4) if the baby's weight is at least 1,000 g. 71% perform the repair before
      discharge. The pain control choice after childhood IH repair is Tylenol for 30%,
      local infiltration biquivacaine for 30%, caudal block for 22%, regional block for
      11%, and Tylenol/codeine combined for 7%. In 6-week-old full-term infants with
      communicating hydroceles without definite "hernia," two thirds treat as an IH
      with elective repair as soon as possible. With respect to contralateral
      exploration in infants with unilateral IH, 65% perform it in males if they are <
      or = 2 years of age and 84% use it in females of up to 4 years of age. This
      approach is not influenced by presenting side, presence of hydrocele, or history
      of prematurity. Laparoscopic evaluation of the contralateral IH is performed by
      only 6% of responders, 40% of whom use the open ipsilateral sac for laparoscope
      introduction.

PMID- 8863258
TI  - Laparoscopic evaluation for contralateral patent processus vaginalis: Part II.
AB  - Between May 1,1992 and August 1, 1995, 599 consecutively treated children under
      10 years of age evaluated by the authors for a known inguinal hernia were
      involved in a prospective protocol to determine whether diagnostic laparoscopy
      has a place for evaluation of the contralateral inguinal region. The experience
      with the first 221 patients was reported at the 1993 AAP meeting. In this total
      experience, 81 patients had known bilateral inguinal hernias and did not require
      diagnostic laparoscopy. Five hundred eighteen patients had a unilateral inguinal
      hernia with the status of the contralateral region being unknown. Between May 1,
      1992 and May 1, 1994, 368 children underwent evaluation using an umbilical
      approach. However, for the past 14 months, 150 patients have undergone the
      diagnostic laparoscopy through the ipsilateral hernia sac. Among the children
      under 1 year of age, 98 were found to have a unilateral hernia and also a
      contralateral patent processus vaginalis (CPPV) and 110 had a unilateral hernia.
      Of the children older than age 1,116 had a unilateral hernia and CPPV and 194 had
      only a single hernia. After induction of anesthesia, it was suspected on clinical
      examination that 195 of the 518 patients had a CPPV. However, laparoscopy showed
      that only 94 (48%) had a CPPV. In the remaining 323 patients, the surgeon
      believed that a CPPV was not present based on the examination. This negative
      finding was verified in only 198 patients (81%), but a surprising 125 (39%) did
      have CPPV documented at the time of endoscopy. Insufflation alone was very
      unrellable for documenting the presence of CPPV. Of the 214 patients for whom
      CPPV on the contralateral side was documented during laparoscopy, only 41 (19%)
      had a positive finding on insufflation. This experience has convinced the authors
      that diagnostic laparoscopy is the most accurate means to ascertain whether a
      patient should undergo contralateral inguinal exploration. In addition,
      laparoscopy through the ipsilateral inguinal sac is now the preferred approach.

PMID- 8863259
TI  - Laparoscopy through the open ipsilateral sac to evaluate presence of
      contralateral hernia.
AB  - PURPOSE: Laparoscopic evaluation of the contralateral side (LECS) in children
      with unilateral inguinal hernia (UIH) has been criticized because of the
      abdominal trocar risk and costs. LECS was modified to avoid abdominal trocar
      insertion by using the open hernia sac for instrumentation (OHLECS). This study
      was performed to determine the utility, safety, and effectiveness of this
      technique. METHODS: During a 15-month period, 80 children with unilateral hernia
      underwent attempted OHLECS. All ordinarily would have undergone open
      contralateral exploration. The indications were UIH in boys < or = 2 years of age
      and girls < or = 4 years of age (n = 53) or high clinical suspicion (but not
      certainty) of contralateral hernia in older children with UIH (n = 27).
      Endotracheal intubation was not used unless otherwise indicated. Reusable 3-mm
      blunt trocars and 3-mm 30 degrees or 70 degrees laparoscopes were employed, with
      and 6 to 8 mm of insufflation pressure. No urethral catheter was used. The
      ipsilateral hernia sac was dissected, opened, and instrumented, and the
      contralateral side was evaluated for patency. Concurrent external palpation of
      the contralateral inguinal canal is an important diagnostic adjunct. Positive
      results were visible patency of processus vaginalis or bubbles or fluid and/or
      gas expressed from the processus by palpation. Only if the evaluation was
      positive was contralateral incision and repair performed. OHLECS added no more
      than 2 minutes of operating time. The operating room cost is similar to that of
      opening the contralateral side. Only reusable laparoscopic instruments are used,
      and less operating time, anesthetic time, suture material, and dressings are
      required if the contralateral side is not opened. RESULTS: In 10 patients (all <
      6 months old) OHLECS was aborted because the hernia sac was smaller than 3 mm at
      the internal ring. OHLECS was successful in 70 (88%) patients-56 boys and 14
      girls, aged 2 mo to 12 years (mean, 2.6 years). The presenting hernia was right
      sided in 46 (66%) and left-sided in 24 (34%). Overall, 43 (61%) OHLECS results
      were negative and 27 (39%) were positive. The OHLECS results were positive for 22
      (39%) boys and 5 (36%) girls. Their mean age was 1.9 years (range, 2 months to 10
      years). There were no false-positives and one false-negative. There have been no
      complications during follow-up (mean, 1.14 years; range, 6 months to 2 years). No
      additional costs were incurred because nondisposable equipment was used.
      CONCLUSION: Laparoscopic evaluation of the contralateral side via the open
      ipsilateral hernia sac is feasible, quick, safe, cost effective, and requires no
      additional incisions. The rate of positive findings is comparable with that of
      open exploration. Long-term follow-up is required to determine the ultimate
      effectiveness of the technique.

PMID- 8863260
TI  - Clinical judgment is superior to diagnostic tests in the management of pediatric
      small bowel injury.
AB  - Traumatic solid organ injuries are easily recognizable on computed tomography
      (CT) scans and usually are treated nonoperatively. Small bowel injuries may be
      difficult to diagnose and require prompt operation. This study was done to assess
      the role of clinical examination versus diagnostic tests in evaluating these
      injuries. The medical records of all pediatric (< or = 18 years old) patients
      treated at a pediatric trauma center from 1984 to 1995 were reviewed. Statistical
      analysis was performed using SAS software, with P values of less than .05
      considered significant. Small bowel injury occurred in 48 patients (21 blunt, 27
      penetrating). Most blunt injuries were automobile-related (11 patients) or
      attributable to recreational activities (4) or bicycle accidents (2). Penetrating
      injuries were primarily caused by assaults with guns (21) or knives (4). All
      conscious patients with small bowel injury had abnormal physical examination
      findings at the time of presentation. Nineteen patients had generalized
      peritonitis, and 14 had localized abdominal tenderness. The serum amylase level
      was abnormal in 2 of 18 cases. Abdominal CT scans were obtained in six patients
      and showed the injury in only three. Peritoneal lavage (DPL), performed in 10
      patients, led to the diagnosis in five. There was no significant difference in
      the complication rate (30%) between patients operated on immediately because of a
      diagnostic test result and those operated on later, after a period of clinical
      observation (P = 1.0, Fisher's Exact test). Associated injuries were common (60%)
      among both blunt and penetrating cases. In this nonoperative era of pediatric
      trauma care, small bowel injury is best diagnosed clinically. The physical
      examination is 100% sensitive in the conscious patient, and specificity is
      achieved by serial examination. Serum amylase, CT scan, and DPL are not reliable
      diagnostic tests to exclude these injuries. Patients can be observed until
      physical findings suggest bowel injury without increased morbidity. Associated
      injuries are common; thus, patients are best treated where multidisciplinary
      support is available.

PMID- 8863261
TI  - Helicopter transport of injured children: system effectiveness and triage
      criteria.
AB  - The authors compared air and ground transport to a level I pediatric trauma
      center to assess the effectiveness of helicopter transport of injured children.
      They also performed a retrospective assessment of triage criteria and utilization
      patterns for helicopter transports. The sample comprised 3,861 children who were
      admitted (consecutively) to an urban level I pediatric trauma center during a 4
      year period and who were transported by emergency medical services. TRISS
      probability of survival (P2),z, and W scores were used to compare outcomes of
      ground and air transports. An absolute value of z greater than 1.96 indicates a
      statistically significant difference in mortality rate; the W statistic
      represents the number of survivors more than expected per 100 patients treated.
      Receiver operator characteristic (ROC) curves were used to identify optimal
      triage criteria, using P6 < .95 to define children who potentially could benefit
      from air transport. The triage criteria were applied to the air transport group
      to determine overtriage rates. Nearly 75% of the children arrived directly from
      the scene of injury. Those transported by air were more severely injured, as
      shown by significant differences in the mean Glasgow Coma Scale (GCS), P6, Injury
      Severity Score, and mortality rate. The better survival rate for children
      transported by helicopter was indicated by a TRISS z score of 2.81, compared with
      a z score of 0.31 for those transported by ambulance. The W statistic for the
      children transported by air was 1.11. ROC analysis identified GCS < 12 and heart
      rate > 160 beats per minute as optimal air triage criteria; these yielded 99%
      sensitivity and 90% specificity. Using these criteria, approximately 85% of air
      transports would be considered overtriage. The authors conclude that (1)
      helicopter transport was associated with better survival rates among urban
      injured children; (2) pediatric helicopter triage criteria based on GCS and heart
      rate may improve helicopter resource utilization without compromising care; and
      (3) current air triage practices result in overuse of helicopters in
      approximately 85% of flights.

PMID- 8863262
TI  - Penetrating hepatic trauma in children: operating room or not?
AB  - Nonoperative management has become widely accepted as the standard of care for
      patients with blunt hepatic trauma. Recent studies among adults have supported
      the use of nonoperative management of selective penetrating wounds to the hepatic
      bed in stable patients. The therapeutic management of children with penetrating
      injuries to the hepatic bed were evaluated to ascertain whether nonoperative
      management was a reasonable consideration in their care. The database of the
      National Pediatric Trauma Registry (NPTR) was reviewed for the period 1985-1994.
      ICD-9 codes 864.00 to 864.10 were used to select injury site, diagnosis, and,
      combined with Current Procedural Terminology (CPT) code data, to ascertain
      therapeutic interventions. The NPTR is a compilation of data from 61 pediatric
      trauma centers, currently held at Tufts University. The charts of 29,000 children
      were reviewed; of these, 1,147 sustained hepatic injuries, 132 (12%) of whom had
      a penetrating injury. The mechanism of injury was gunshot wound in 100 patients
      (76%) and stab wound in 32 (24%). The mean age of the children who had a
      penetrating injury was 12.7 years (range, in utero to 19 years). Six children
      were managed nonoperatively (5%), and 20 (15%) had negative laparotomy findings.
      Overall, 106 children sustained additional injuries that required surgical
      repair. There were 50 hollow viscous injury repair, 19 diaphragmatic repairs, 5
      nephrectomies, 4 splenectomies, 4 pancreatic resections, and 43 significant
      hepatic repairs. The overall mortality rate was 9.8% (13 deaths). Nine of these
      patients died within 24 hours of injury. These data indicate that penetrating
      injury to the hepatic bed in children is associated with a high percentage of
      other organ injuries that require surgical intervention. This seems to be in
      direct contrast with the findings for adults, for whom the hepatic mass appears
      protective because of its larger size. The close anatomic proximity of the organs
      in a child's abdomen appears to make surgical intervention necessary for the
      majority of children with penetrating injury to the hepatic bed, and indicates
      that this approach should remain the standard of care for pediatric patients.

PMID- 8863263
TI  - Pseudoaneurysm formation is a known complication of both arterial manipulations
      and arterial injuries.

PMID- 8863264
TI  - Laparoscopic pyloromyotomy for infantile hypertrophic stenosis.

PMID- 8863265
TI  - A nomogram to predict the best biological half-life values for candidates for
      oral prolonged-release formulations.
AB  - It is sometimes possible to maintain plasma concentrations between desired
      maximum and minimum limits by repetitively administering a drug in an oral
      prolonged-release formulation when this goal cannot be achieved with a rapid
      release formulation. However, this approach does not work with all drugs. The
      biological half-life value of the drug can be one cause for failure of this
      approach. Although it is recognized that a half-life may be too long or too
      short, neither the criteria for determining these values nor the consequences of
      failing to meet them have been established. The best half-life values for
      prolonged-release candidates were found by simulating once-a-day and twice-a-day
      administration of formulations and examining the capacity of these formulations
      to maintain steady-state plasma concentrations between various selected limits.
      These observations were used to establish criteria to judge the acceptability of
      half-lives. Half-life values were considered too long if drugs were self
      sustaining and simulations of their rapid-release formulations were also
      successful. Half-life values were considered too short if minor variability in
      prolonged-release rates resulted in plasma concentrations above and/or below the
      selected limits. The actual half-life values that were considered too long or too
      short depended on the dosing interval and the selected maximum and minimum plasma
      concentrations. A nomogram was constructed to assess the acceptability of the
      biological half-life of a candidate for once-a-day or twice-a-day prolonged
      release formulations. The nomogram employs the user-selected limits for the
      desired plasma concentrations to predict whether the half-life of a candidate is
      (1) too long, (2) too short, or (3) acceptable (i.e., between 1 and 2).

PMID- 8863266
TI  - Prediction of binding constants of alpha-cyclodextrin complexes.
AB  - Proceeding from a phenomenological theory of pairwise interactions (solvent
      solvent, solvent-solute, and solute-solute), the binding constant K11 (in M-1)
      for 1:1 complex formation by alpha-cyclodextrin at a substrate binding site, at
      25 degrees C in water, is given by log K11 = -1.74 - [Z] + 0.032(-delta A), where
      [Z] incorporates solvent-solute (solvation) and solute-solute interactions and
      delta A is the decrease in nonpolar surface area (in A2 molecule-1) on the
      substrate that is exposed to solvent when the binding site enters the
      cyclodextrin cavity. delta A is estimated from the structure of the binding site.
      Three levels of approximation are described for estimating [Z]. At the third
      (highest) level, the procedure when applied to 569 complex systems generated
      predicted values of log K11 that agreed within 0.30 unit of the experimental
      values in 58% of cases, and that agreed within 1.00 unit in 95% of cases.

PMID- 8863267
TI  - Interaction of norfloxacin with divalent and trivalent pharmaceutical cations. In
      vitro complexation and in vivo pharmacokinetic studies in the dog.
AB  - The formation constants of the fluoroquinolones norfloxacin and ciprofloxacin
      with Mg2+ (log beta 1 = 2.97(4), log beta 2 = 5.6(2)), Zn2+ (log beta 1 =
      3.77(2), log beta 2 = 7.59(3)), and Fe2+ (log beta 1 = 3.99(5), log beta 2 =
      7.2(5)) were determined by potentiometric titration. The pH at which
      precipitation occurred in the titration solutions was compared for the metal ions
      Ca2+, Mg2+, Zn2+, Fe2+, Cu2+, and Al3+. The formation constants were used to
      predict a rank order of metals that may be expected to hinder the
      gastrointestinal absorption of the fluoroquinolones, in vivo. The effects of
      metal ions on the pharmacokinetics of orally-administered norfloxacin in the dog
      were investigated. Norfloxacin (12 mg/kg) was administered alone or with
      equimolar doses of each of the chloride salts of Ca2+, Mg2+, Zn2+, Fe2+, and
      Al3+. Statistically significant reductions in serum norfloxacin concentrations
      were observed after analysis by HPLC. The Cmax was reduced 29-85%, while the area
      under the norfloxacin serum concentration-time curve (AUC0-infinity) was reduced
      by 29-79%. The extent of the reduction in AUC0-infinity was correlated with the
      magnitude of the formation constant of the 1:1 norfloxacin:metal chelate complex
      for the divalent metal ions. On coadministration of 12 mg/kg norfloxacin with
      various doses of Mg2+ (chloride) the AUC0-infinity and Cmax decreased with
      increasing Mg2+ dose. The interaction peaked at a Mg2+:norfloxacin ratio of 1:2
      suggesting the formation of a 1:2 Mg:norfloxacin complex. Formation constant data
      were used to simulate the percentage of norfloxacin complexed at pH 6.5.
      Combinations of metal ion and norfloxacin which result in only a small extent (<
      20%) of norfloxacin complex formation can result in relatively large decreases in
      oral bioavailability of this antimicrobial agent.

PMID- 8863268
TI  - Antiradiation compounds. 24. Stability of copper (II) complexes of
      bis(methylthio) and methylthio amino derivatives of 1-methylpyridinium- and 1
      methylquinolinium-2-dithioacetic acids in the presence of amino acids, simple
      peptides, and a protein.
AB  - The radiation-protective bis(methylthio) and methylthio amino derivatives of 1
      methylpyridinium- and 1-methylquinolinium-2-dithioacetic acids, a series of non
      thiol sulfur-containing compounds, have been examined for their ability to
      complex Cu(II) ion and remain stable in the presence of alpha-amino acids,
      peptides, and a protein. Copper-binding stability constants were found that were
      considered sufficiently large to be capable of existence under cellular
      conditions, with log K beta values in the range of 13-15. Copper-binding
      constants for alpha-amino acids are comparable to those for the radioprotective
      ligands, but overall binding constants for simple peptides are usually 10(4)
      10(6) lower in magnitude. Essentially no change was found in the UV spectra of
      the Cu(II) complexes in the presence of alpha-amino acids and simple peptides,
      and the binding capacity to bovine serum albumin was quite low for two Cu(II)
      complexes of the best protective ligands, with values of 10(-6)-10(-7) M. The
      possibility that these radioprotectors may act in vivo as copper complexes,
      possibly as superoxide dismutase mimics, is thus feasible. The magnitude of the
      copper-binding stability constants, the lack of copper exchange between the
      radioprotective ligands and amino acids or peptides, and the very low tendency of
      the copper complexes of the radioprotective ligands to bind to a protein indicate
      the potential of the complexes to contribute to the radioprotective ability of
      the ligands.

PMID- 8863269
TI  - Synthetic nucleosides and nucleotides. 37. Antisense oligodeoxynucleotides
      bearing 5-(phenylethyl)-2'-deoxyuridylate at the 3'-terminus: exonuclease
      resistant molecule with natural phosphodiester backbone.
AB  - 5-(Phenylethyl)-2'-deoxyuridine has been incorporated into an
      oligodeoxynucleotide (ODN) by using normal cyanoethyl phosphoramidite chemistry
      on a DNA synthesizer. For introduction of the modified residue at the 3'-end
      position of the ODN, we designed and synthesized a new nucleoside phosphoramidite
      derivative, which connected the 3'-hydroxyl group and phosphoramidite moiety by
      an alkaline-labile linker. The 3'-end could be substituted in ODNs by using
      commercially available supports as a starting material following standard NH4OH
      treatment. The ODN carrying 5-(phenylethyl)-2'-deoxyuridine at the 3'-end
      position showed about 3-fold resistance to nucleolytic degradation in human
      plasma without precluding its specific base-pairing activity.

PMID- 8863270
TI  - Unified model for the corneal permeability of related and diverse compounds with
      respect to their physicochemical properties.
AB  - Corneal permeability data taken from the literature were analyzed for possible
      quantitative relationships with physicochemical properties. Although a parabolic
      relationship was obtained with good correlation between lipophilicity, as
      expressed by the 1-octanol-water partition coefficients, log Poctanol (or the
      distribution coefficients, log D for ionizable compounds), and the permeability
      in individual analyses of compound classes such as beta-adrenoceptor blockers and
      steroids, the correlation was reduced when taken together. However, delta log P
      (i.e., log Poctanol-log Palkane) correlated inversely with the combined
      permeability data for beta-blockers and steroids and played a key role as a
      unifying variable. To a lesser extent, lipophilicity itself also contributes
      positively to corneal permeation. Even with the addition of miscellaneous
      compounds such as methanol and ibuprofen, the delta log P and lipophilicity terms
      were still significant. However, small molecules were likely to be
      underestimated, which is consistent with penetration via another pathway besides
      that governed by delta log P and lipophilicity.

PMID- 8863271
TI  - Pharmacokinetics of cisplatin and its monohydrated complex in humans.
AB  - The pharmacokinetics of cisplatin and its cytotoxic hydrolysis product cis
      diammineaquachloroplatinum(II) ion (monohydrated complex) were investigated in
      seven patients after they received a 1-h infusion of cisplatin in normal saline
      at 100 mg/m2. The concentrations of intact cisplatin and the monohydrated complex
      were determined in blood by liquid chromatography with post-column
      derivatization, using diethyldithiocarbamate as the reagent. A pharmacokinetic
      model was developed assuming that a fraction of the dose (2.3%) is present as the
      monohydrated complex in the infusion solution and that reversible reactions
      between cisplatin and its monohydrated complex prevail. The clearances of
      cisplatin and the monohydrated complex were 0.32 +/- 0.05 and 0.27 +/- 0.11
      L/min/m2, respectively. The apparent volume of distribution was considerably
      smaller for the monohydrated complex (4 +/- 2 L/m2) than for cisplatin (11 +/- 2
      L/m2). The elimination rate constants were 0.030 +/- 0.002 and 0.07 +/- 0.02 min
      1 for cisplatin and the monohydrated complex, respectively. The area under the
      time-concentration curve for the monohydrated complex was approximately 15% of
      that for cisplatin. It is concluded that the significant amounts of the
      monohydrated complex present in blood are due to the fraction already present in
      the administered dose and to the fraction formed in blood.

PMID- 8863272
TI  - Prodrugs of BMS-183920: metabolism and permeability considerations.
AB  - The oral bioavailability of BMS-183920, a diacidic, potent angiotensin II
      receptor antagonist, is low in rats (approximately 11%). In vivo studies in bile
      duct-cannulated rats indicated that BMS-183920 was metabolically stable and that
      the low bioavailability was due to incomplete intestinal absorption. Five acyl
      ester prodrugs were synthesized which were 5-15 times more permeable than BMS
      183920 through Caco-2 cells. However, limited studies in rats indicated that the
      oral bioavailability of BMS-183920 was improved only 2-fold, in the best case.
      The lack of a substantial increase in bioavailability was apparently due to
      presystemic prodrug hydrolysis or metabolism via N-glucuronidation.
      Bioavailability of BMS-183920 after oral dosing of a tetrazole-ester prodrug
      averaged 37%, the most significant improvement within this prodrug series.
      Interestingly, in vitro studies indicated that the tetrazole-ester prodrug was a
      substrate for glucuronosyl transferase; however, its rate of bioactivation
      (hydrolysis) was sufficiently high to provide a substantial increase in
      bioavailability of BMS-183920. Therefore, while prodrug modification of BMS
      183920 improved Caco-2 cell permeability and oral absorption in vivo, the
      relative extents of hydrolysis (bioactivation) vs metabolism of the prodrug
      determined whether a substantial improvement in bioavailability was achieved.

PMID- 8863273
TI  - Solid phases of delavirdine mesylate.
AB  - Delavirdine mesylate was recrystallized from solution under a variety of
      conditions. Seven crystal forms and a stable amorphous phase were isolated from
      solution. Two of these crystal forms were polymorphic anhydrates: from XI (U
      90152T) and form VIII (U-90152S). Two hydrates (forms VI and XIV), an ethanol
      solvate (form VII), an acetonitrile solvate (form XIII), and a solvate from
      methanol/acetone (from XII) were also identified. Six additional phases were
      identified as the products of solid-state transformations of the hydrated and
      solvated phases. The solid phases were differentiated by infrared spectroscopy
      and X-ray powder diffraction. Several of the solid-state phase transformations
      were mediated by atmospheric moisture. These transformations were studied as a
      function of relative humidity with dynamic moisture sorption gravimetry (DMSG).
      DMSG also provided useful measurements of hygroscopicity.

PMID- 8863274
TI  - Evaluation of ketorolac concentrations in plasma and gingival crevicular fluid
      following topical treatment with oral rinses and dentifrices.
AB  - Two clinical studies were conducted to determine the relative amounts of
      ketorolac detectable locally in the gingival crevicular fluid (GCF) and
      systemically in plasma after oral, topical drug administration. The rinse study
      compared topical administration of three concentrations of ketorolac tromethamine
      (0.1%, 0.5%, and 0.01%) in oral rinse formulations administered topically and a
      perorally administered capsule (10 mg), and the dentifrice study compared two
      concentrations of ketorolac in dentifrice formulations (0.15% and 1.0%) with a
      0.1% oral rinse, all treatments administered topically. The dose-corrected
      systemic availability of the three oral rinses evaluated in the rinse study
      relative to the peroral capsule was about 15%. However, the ratios of the
      observed maximum GCF ketorolac concentration to maximum plasma ketorolac
      concentration ranged from 22 to 49, compared to less than 1 for the peroral
      ketorolac capsule. Using this ratio as an estimate of the ability of a treatment
      to target the drug to the gingival tissue, these data indicate that the ketorolac
      oral rinses achieved greater delivery of drug to the gingival tissue (presumed
      site of action for periodontitis) with a lower systemic drug load than peroral
      administration of a ketorolac capsule. The dose-corrected relative systemic
      bioavailabilities for the dentifrice treatments with respect to the 0.1% rinse in
      the dentifrice study were 59.2% and 86.4% for the 1.0% and 0.15% dentifrices,
      respectively, indicating that significantly less ketorolac was systemically
      available from the two dentifrices relative to the oral rinse. The relative
      bioavailabilities of ketorolac in the GCF after dosing with the dentifrice
      formulations with respect to the rinse were 89.1% for the 1.0% dentifrice and
      19.7% for the 0.15% dentifrice. Thus, the 1.0% dentifrice appears to provide
      statistically equivalent levels of ketorolac to the gingival tissue as the 0.1%
      oral rinse with significantly less systemic exposure. The T1/2 of ketorolac in
      the GCF was about 0.5 h for all three treatments, which is significantly less
      than the plasma half-life of about 5.3 h. These data suggest that GCF levels of
      ketorolac should remain above the IC50 for PGE2-stimulated IL-1 bone resorption
      for about 7 h following treatment, assuming continuation of the first-order
      elimination observed over the first two postdosing hours. We conclude that oral
      rinses and dentifrices are effective and preferred vehicles for administration of
      ketorolac for use in treatment of periodontitis.

PMID- 8863275
TI  - Self-association of nicotinamide in aqueous solution: light-scattering and vapor
      pressure osmometry studies.
AB  - Nicotinamide is a hydrotropic agent that has been reported to self-associate in
      aqueous solution. The objective of this study is to characterize the self
      association of nicotinamide with regard to the extent of self-association as well
      as association constants using light-scattering and vapor pressure osmometry.
      Both methods allow calculation of association constants; however, while light
      scattering measurements depend on the size of particles in solution, vapor
      pressure osmometry depends on the number of particles in solution. Using light
      scattering, nicotinamide was found to associate primarily as dimers and trimers.
      Higher order aggregates can be characterized by an average aggregation number of
      4.37. The association constants were 9.99 L/mol and 13.1 L/mol for dimerization
      and trimerization, respectively. From vapor pressure osmometry data were
      calculated a dimerization constant of 0.203 L/mol and a trimerization constant of
      14.1 L/mol. In comparison, the trimerization constants are in good agreement,
      while the dimerization constants differ by an order of magnitude. Since light
      scattering measurements are less reliable for small molecules like nicotinamide
      at low concentrations, it is felt that the dimerization constant calculated from
      vapor pressure osmometry is the more accurate.

PMID- 8863276
TI  - Improvement of intestinal absorption of leucine enkephalin by sugar coupling and
      peptidase inhibitors.
AB  - Peptidase-degradable leucine enkephalin (LE) was coupled with cellobiose or
      gentiobiose. In the absorption experiments, cellobiose-coupled LE (CcpLE) was
      more stable than LE itself on the mucosal side, and CcpLE appeared on the serosal
      side. Destyrosyl LE coupled with cellobiose was not formed, indicating that sugar
      coupling provided LE with aminopeptidase resistance. In the presence of
      inhibitors of angiotensin-converting enzyme and enkephalinase, the stability of
      CcpLE on the mucosal side was increased, and as a result more was absorbed.
      Furthermore, the absorption clearance was much higher than the value expected
      from the mucosal concentration of CcpLE. Similar results were observed in the
      absorption of gentiobiose-coupled LE. In the LE absorption experiment, however,
      LE was not detected on the serosal side even in the presence of these peptidase
      inhibitors. Improvement of intestinal absorption by sugar coupling and peptidase
      inhibitors was evaluated kinetically, indicating the exclusive contribution of
      metabolic degradation of LE through intestinal tissues to the absorption process.

PMID- 8863277
TI  - Effects of protease inhibitors on the absorption of phenol red and fluorescein
      isothiocyanate dextrans from the rat intestine.
AB  - The absorption enhancement effects of three types of protease inhibitors,
      aprotinin, bacitracin, and soybean trypsin inhibitor, on the small and large
      intestinal absorption of phenol red (PR) and fluorescein isothiocyanate dextrans
      (FDs) were examined in rats. Of these protease inhibitors, only bacitracin
      enhanced the absorption of PR and FDs from the rat small and large intestine.
      Thus, we suggest that bacitracin has not only a protease-inhibitory but also an
      absorption-enhancing capability. We examined the effects of various protease
      inhibitors on intestinal mucosal toxicity by measuring the leakage of Evans blue
      (EB) from the systemic circulation. Although there was a significant increase in
      the leakage of EB in the presence of bacitracin, it was considerably less than
      that in the case of polyoxyethylene 9-lauryl ether (BL-9), which was used as a
      positive control. Therefore, bacitracin may be a good model adjuvant for
      improving the intestinal absorption of poorly absorbable drugs because it did not
      cause serious intestinal mucosal damage, as seen in the case of BL-9.

PMID- 8863278
TI  - Myocardial pharmacokinetics of thiopental in sheep after short-term
      administration: relationship to thiopental-induced reductions in myocardial
      contractility.
AB  - The myocardial kinetics and dynamics of thiopental (750 mg over 2 min) were
      examined in chronically instrumented sheep (five studies in four sheep). The
      myocardial kinetics were studied by simultaneous rapid sampling of arterial and
      coronary sinus blood for 30 min. The myocardial kinetics for four of the five
      studies were best described by a single flow-limited compartment with apparent
      volumes of between 42 and 113 mL. These volumes equated to half-lives of
      equilibration between blood and myocardium of between 0.49 and 1.00 min when
      baseline blood flow was taken into account. The remaining study was better
      described by a model with a slight membrane limitation (permeability/flow ratio
      of approximately 2). Myocardial contractility was studied as a measure of
      myocardial pharmacodynamics and was reduced to 53% of baseline at approximately
      2.5 min after the start of the dose. Effect compartment analysis showed that
      there was hysteresis between the time course of these contractility changes and
      the time course of the arterial concentrations, with effect compartment half
      lives between 0.08 and 0.87 min. There was significantly less hysteresis for the
      coronary sinus concentrations. It is concluded that thiopental equilibrated
      rapidly with a component of the myocardium, and that consequently its effects on
      myocardial contractillity also rapidly equilibrated with both afferent and
      effluent myocardial blood.

PMID- 8863279
TI  - Inhibitory effect of sugars and polyols on the metal-catalyzed oxidation of human
      relaxin.
AB  - Previously, our laboratory (Li, S.; et al. Biochemistry 1995, 34, 5762-5772)
      showed that the oxidation of recombinant human relaxin (Rix) could be induced by
      ascorbic acid (AsA)/Cu(II), a system used for the metal-catalyzed generation of
      reactive oxygen species. In this study, we observed that this oxidation could be
      inhibited by high concentrations of mannitol and other sugars and polyols, such
      as ethylene glycol, glycerol, glucose, and dextran. Similar protective effects
      with high concentrations of mannitol were also observed in the AsA/CuCl2-induced
      oxidation of Gly-Met-Gly and Gly-His-Gly. In contrast, (carboxymethyl)cellulose
      had no protective effect on the metal-catalyzed oxidation of Rix. These results,
      together with results from deuterium isotope experiments and spectroscopic
      experiments, suggest that the inhibitory effect of polyols and sugars is probably
      due to the complexation of transition metal ions rather than a hydroxyl radical
      scavenging mechanism. However, dextran, a high molecular weight polysaccharide,
      might function as a hydroxyl radical scavenger to protect Rix from the metal
      catalyzed oxidation.

PMID- 8863280
TI  - Effects of reducing sugars on the chemical stability of human relaxin in the
      lyophilized state.
AB  - Sugars and polyols have been used routinely with lyophilized proteins and
      peptides as bulking agents, cryoprotectants, and lyoprotectants. However,
      reducing sugars may present a problem as excipients since they are potentially
      reactive with proteins. In this stability study of recombinant human relaxin
      (Rix) with various sugars as excipients in lyophilized formulations, we observed
      rapid covalent modifications of the protein in the presence of glucose. Analysis
      of the protein by LC/MS and tryptic mapping indicated two major degradation
      pathways. Covalent adducts of glucose with amino groups on the side chains of the
      protein (i.e., Lys and Arg) formed via the Maillard reaction. In addition, a
      significant amount of Ser cleavage from the C-terminal of the B-chain of relaxin
      was also identified when glucose was used as the excipient. It was observed that
      the latter reaction occurred to a greater extent in the solid state than in
      solution. We proposed a mechanism for this reaction involving an initial reaction
      of the Ser hydroxyl group with glucose followed by subsequent hydrolysis of the
      Trp-Ser amide bond via a cyclic intermediate. In contrast to glucose, mannitol
      (polyhydric alcohol) and trehalose (nonreducing sugar) produced stable,
      lyophilized formulations of Rix.

PMID- 8863281
TI  - Preliminary physiologically based pharmacokinetic model for cocaine in the rat:
      model development and scale-up to humans.
AB  - A physiologically based multicompartmental model has been developed to describe
      the concentration-time course of cocaine in plasma and tissues in the rat. The
      compartments included in the model were brain, heart, gut, liver, muscle, fat,
      venous blood, arterial blood, and a mass-balance compartment. Drug delivery to
      the tissues was assumed to be flow limited. The model incorporated a nonsaturable
      binding site for cocaine in the liver. Elimination occurred via both blood and
      hepatic elimination. The model was validated using independently derived data.
      The model was scaled to humans and accurately predicted the cocaine levels
      following intranasal and inhalation administration. However, a poor fit was
      observed following intravenous administration. Future models incorporating non
      constant blood flow and pharmacodynamics need to be developed.

PMID- 8863282
TI  - The variance of a better AUC estimator for sparse, destructive sampling in
      toxicokinetics.

PMID- 8863283
TI  - Determination of the steady state tissue distribution of midazolam in the rat.
AB  - The aim of this study was to determine the steady state tissue:blood (Kb),
      tissue:plasma (Kp), and tissue:plasma water (Ku) partition coefficients of
      midazolam in all major organs and tissues in the rat, after development of a gas
      chromatographic assay. The Kp in 12 tissues ranged between 1.3 (in muscle) and
      9.0 (in fat). Ku ranged correspondingly between 16 and 115.

PMID- 8863284
TI  - High-performance liquid chromatographic analysis of 2'-fluoro-2',3'
      dideoxyadenosine and 2'-fluoro-2',3'-dideoxyinosine in dog plasma and urine.
AB  - A high-performance liquid chromatographic assay was developed and validated for a
      simulataneous determination of 2'-fluoro-2' 3'-dideoxyadenosine (FddA) and its
      metabolite, 2'-fluoro-2',3'-dideoxyinosine (Fddl) in dog plasma and urine. In
      vitro, FddA and Fddl exhibit activity against human immunodeficiency virus (HIV).
      A solid phase extraction was applied to extract FddA, Fddl, and the internal
      standard (IS; 3',5'-anhydrothymidine) from the biomatrices. The processed samples
      were chromatographed using a C8 column coupled with a mobile phase consisting of
      monobasic phosphate, dibasic phosphate, ethylene glycol monomethyl ether, and
      water. Detection was performed at 257 nm. The nominal retention times were 9, 14,
      and 26 min for Fddl, IS, and FddA, respectively. The lower limits of quantitation
      were 0.1 and 2.0 micrograms/mL in plasma and urine, respectively, for both
      analytes. The accuracy of the assay deviated < or = 10% from the nominal
      concentrations, and the precision was < or = 14% coefficient of variation. In
      either matrix, both analytes were stable for at least three freeze-thaw cycles
      and in the injection media for at least 54 h. The extraction recoveries of the
      analytes were greater than 80%. The application of this assay was demonstrated in
      a preliminary pharmacokinetic study of FddA and Fddl in dogs. Two male dogs per
      dose level received a 100, 250, or 500 mg/kg oral dose of FddA once daily for 14
      days. The early appearance of Fddl in plasma (0.25 h; the first sampling time)
      and greater plasma levels of Fddl than FddA (> 50-fold of Cmax), suggested that
      the conversion of FddA to Fddl was rapid and extensive. Renal excretion appeared
      to be the major route of elimination of Fddl.

PMID- 8863285
TI  - Rectal absorption of omeprazole from suppository in humans.
AB  - The oral absorption of omeprazole is incomplete, in part due to first-pass
      metabolism. We investigated the feasibility of rectal administration of
      omeprazole by comparing its absorption from a Witepsol H15-based rectal
      suppository and an orally administered commercial gelatin capsule in 10 male
      volunteers. Profiles of plasma concentration between two preparations (20 mg)
      were not statistically different, indicating that the rate and the extent of
      absorption were similar. Paired t-test revealed no significant differences in
      area under the curve, mean residence time, and time to peak concentration between
      two preparations. On the other hand, lag time of absorption and peak
      concentration were statistically different (p < 0.05) between these preparations.
      Under these experimental conditions, the rectal route did not produce an
      improvement in the extent of absorption over an oral capsule.

PMID- 8863286
TI  - Isolation and measurement of colloids in human plasma by membrane-selective flow
      field-flow fractionation: lipoproteins and pharmaceutical colloids.
AB  - Using a modified flow field-flow fractionation (flow FFF) technique termed
      membrane-selective flow FFF, a capability is developed to isolate various
      colloidal constituents that are naturally present in or may be introduced into
      blood plasma. Once isolated, the colloids may be subject to quantitative
      measurement to provide relative amounts of the different constituents and the
      size distribution curve of each. The potential of the technique has been
      demonstrated by isolating and measuring (a) the lipoprotein fractions found in
      human blood plasma, (b) liposyn II pharmaceutical emulsion added at 2 mg/mL of
      plasma, and (c) amphotericin B colloidal dispersion (a drug delivery agent) added
      to plasma at 0.5 mg/mL.

PMID- 8863287
TI  - Bioavailability of intranasal scopolamine in normal subjects.
AB  - The bioavailability of scopolamine in three dosage forms was compared in 12
      healthy nonsmoking male volunteers. Subjects received 0.4-mg doses of scopolamine
      bromide in intravenous (i.v.), intranasal (i.n.), or oral (p.o.) dosage forms on
      three occasions, with at least 2 weeks separating the doses. Scopolamine
      concentrations in plasma were determined with a combined reverse-phase liquid
      chromatographic-radioreceptor binding assay. Saliva volume and flow rate and
      percent suppression of control flow rate were determined from each sample.
      Absorption after i.n. and po scopolamine administration was rapid; plasma
      concentrations [1680 (i.n.) and 164 pg/mL (p.o.)] peaked within 1 h of dosing
      [0.37 (i.n.) and 0.78 h (p.o.)], respectively. i.n. and i.v. scopolamine
      suppressed salivary flow rate to similar extents (95% and 99.7%), respectively.
      Times to reach maximum effect were 1.05 and 0.27 h after i.n. and i.v. dosage,
      respectively. Absolute intranasal bioavailability, calculated from the area under
      the drug concentration vs time curve, was found to be significantly greater than
      that of p.o. scopolamine (83% vs 3.7%, p < 0.05). The i.n. route may provide a
      noninvasive, reliable, fast, and effective route for administering scopolamine.

PMID- 8863288
TI  - Quality of life--an outcome of oral health care?

PMID- 8863289
TI  - Using area-based measures of socioeconomic status in dental health services
      research.
AB  - OBJECTIVES: This paper reports the results of a study to assess the value of an
      area-based measure of socioeconomic status in dental health services research.
      METHODS: Data on oral health were collected using a telephone interview survey of
      a random sample of persons aged 50 years and older living independently in
      Ontario, Canada. Postal codes and a computerized census database were used to
      identify the mean household income of the enumeration area in which each subject
      lived. Analyses were undertaken to determine the extent to which the area-based
      measure of household income substitutes for and supplements self-reported
      household income in predicting oral health outcomes. RESULTS: The results
      indicate that the enumeration area mean was not a good predictor of self-reported
      household income in this population. However, the area-based measure identified
      as much variation in nine oral health outcome variables as did the self-reported
      measure. Also, the socioeconomic status of the area in which the subjects lived
      had an effect on health and health-related behaviors that was independent of
      their household socioeconomic status. CONCLUSIONS: The use of area-based measures
      in dental health services research is promising and warrants further exploration.

PMID- 8863290
TI  - The association between developmental enamel defects and caries in populations
      with and without fluoride in their drinking water.
AB  - OBJECTIVES: The purpose of this study was to consider the association between
      developmental enamel defects and dental caries in children from areas with
      different levels of fluoride in their drinking water. METHODS: children (mean age
      = 14.1 +/- 0.3 years) were examined from areas with less than 0.1 ppm (n = 267)
      and 0.7 ppm (n = 196) in their drinking water. These areas were chosen to contain
      subjects with a similar social profile. Two types of enamel defect were
      considered: those consistent with the diagnostic criteria of the Thylstrup
      Fejerskov (TF) index and demarcated opacities. Dental caries was recorded for
      surfaces at the level of the dentinal lesion. RESULTS: Subjects with one or more
      demarcated opacities had more dental caries than those without these opacities
      present. Children with enamel defects scored with the TF index tended to have
      less dental caries than those without these defects present. However, the
      difference was only statistically significant in the area without fluoride in the
      drinking water. CONCLUSIONS: Developmental enamel defects may be useful markers
      of caries susceptibility, which should be considered in the risk-benefit
      assessment for use of fluoride. Further studies are required to clarify the
      relationship between developmental enamel opacities and dental caries and the
      reasons for any associations.

PMID- 8863291
TI  - The association of early dental caries patterns with caries incidence in
      preschool children.
AB  - OBJECTIVES: This study assessed the development of caries in preschool children
      over two years according to baseline caries pattern. METHODS: Connecticut Head
      Start children (n = 142, mean age = 3.8 years) were examined for dental caries at
      baseline (spring 1991) and once annually for two years. Children were categorized
      at baseline as caries-free, having pit and fissure (PF) caries, or having
      maxillary anterior (MA) caries. RESULTS: After two years, children who presented
      at baseline with MA or PF caries had a mean posterior dmfs of greater than seven
      and four times, respectively, that of children who were caries-free at baseline.
      When dental caries of the primary dentition was categorized by specific posterior
      patterns (i.e., posterior proximal [PP] and buccal/lingual [BL]), change in dmfs
      for the PP and BL patterns in the group that presented with pit/fissure caries at
      baseline were nearly four and three times greater, respectively, than for those
      in the caries-free group. The group that presented with maxillary anterior caries
      at baseline had PP and BL caries increments eight times those of children who
      began caries-free. CONCLUSION: Dental caries presentation in 3- to 4-year-old
      children can identify those children and tooth surfaces that will be at the
      greatest risk for future caries development.

PMID- 8863292
TI  - The state of the nation's oral health: mid-decade assessment of Healthy People
      2000.
AB  - OBJECTIVES: This communication reviews the history and process of establishing
      and assessing national health objectives, presents the status of oral health
      objectives in Healthy People 2000, and summarizes major issues related to the
      outlook for the nation's oral health from the perspectives of participants in a
      July 1995 briefing session with the US Assistant Secretary for Health. METHODS:
      Data obtained from sources such as the third National Health and Nutrition
      Examination Survey-Phase 1, the 1991 Indian Health Service Survey, and 1989-92
      National Health Interview Surveys were examined in relation to specific
      indicators and populations defined at baseline using mid-1980s data. RESULTS:
      Examination of baseline measures and progress data shows that the indicators for
      objectives are, for the most part, stable or improving slightly. Deaths due to
      oral cancer have decreased. Edentulousness is declining. Placement of dental
      sealants on children's teeth is increasing. Adult dental visits are on the
      expected course. Little change has been observed in water fluoridation. Apparent
      declines in dental visits and increases in untreated dental decay for young
      children are potential concerns. Four objectives have no data for progress
      evaluation. CONCLUSIONS: The persistent and often dramatic race-ethnicity and
      socioeconomic differences on many objectives, in combination with possible
      alterations in the public health infrastructure, indicate that concentrated and
      collaborative efforts are needed to achieve Healthy People 2000 targets.

PMID- 8863293
TI  - 1995 Special Merit Award: Howard M. Field, DDS, MPH.

PMID- 8863294
TI  - 1995 Distinguished Service Award: Robert E. Mecklenburg, DDS, MPH.

PMID- 8863295
TI  - Public Service Award: Joe Garagiola.

PMID- 8863296
TI  - The John W. Knutson Distinguished Service Award in dental public health--1995
      recipient Naham C. Cons.

PMID- 8863297
TI  - Leukoplakia, dysplasia, and malignant transformation.

PMID- 8863298
TI  - Hemophilia and EACA.

PMID- 8863299
TI  - Aphthous ulcers and lasers.

PMID- 8863300
TI  - Treatment of large odontogenic keratocysts by decompression and later cystectomy:
      a long-term follow-up and a histologic study of 23 cases.
AB  - OBJECTIVE: The purpose of this study was to determine the course of healing, the
      frequency of recurrence, and the changes in the epithelium of keratocysts after
      decompression treatment. STUDY DESIGN: The treatment of 23 keratocysts, which had
      been divided into two groups (12 and 11 patients, respectively), was carried out
      in two phases: (1) insertion of a polyethylene drain and removal of a biopsy
      specimen from the cyst wall, and (2) cystectomy and removal of the drain
      approximately 1 year later. Histologic examination of the biopsy material from
      the two phases was carried out, and the material classified according to
      Forssell. RESULTS: Reduction in cyst volume together with bone healing occurred
      in all cases, although there was recurrence in two patients. Decompression
      resulted in substantial histologic changes in the epithelium in 19 cases (83%).
      CONCLUSIONS: (1) Decompression results in new bone formation and thickening of
      the cyst wall. (2) This treatment conserves bone and anatomic structures. (3) The
      frequency of recurrence is low. (4) The keratocyst epithelium is modulated
      histologically to nonkeratocyst after decompression.

PMID- 8863301
TI  - Effect of low-level laser treatment on neurosensory deficits subsequent to
      sagittal split ramus osteotomy.
AB  - OBJECTIVES: Low-level laser treatment has been advocated as a possible treatment
      for patients with paresthesia. An objectively verified improvement in sensory
      function is relevant if, at the same time, it is perceived as a subjective
      improvement by the patient. The aim of this double blind clinical study was to
      see if low-level laser treatment with a GaAlAs laser (820 nm, Ronvig, Denmark)
      resulted in objectively verified improvement in sensory function and whether this
      correlated with the patient's subjective evaluation subsequent to treatment.
      STUDY DESIGN: The 13 patients in this study had all undergone saggittal split
      ramus osteotomy resulting in either compression or traction of the inferior
      alveolar nerve as reported by the surgery notes. The material was collected from
      a consecutive series of patients at the Karolinska Hospital, all of whom had
      shown reduced sensibility at their final 2-year postoperative checkup. The
      patients were randomly divided into two groups; one (eight subjects) group
      received real low-level laser treatment (4 x 6 J per treatment along the
      distribution of the inferior alveolar nerve, at the following points extraoral:
      lateral third of lower lip, intraoral; buccally to the apex of the second
      premolar tooth and the apex of the second molar tooth; lingually in the region of
      the mandibular foramen; for a total of 20 treatments). The other group received
      an equivalent placebo treatment. The study was conducted in a double blind
      fashion for both patient and doctor as the low-level laser equipment had two
      settings, A and B, one of which was an unknown void setting. The degree of
      mechanoceptor neurosensory deficit was assessed by Semmes Weinstein monofilaments
      (North Coast Medical, USA) and the degree of thermoceptor neurosensory deficit
      was assessed by a Thermotester (Somedic, Sweden). The degree of subjective
      neurosensory deficit was assessed by means of a visual analogue scale. Both
      variables and the degree of subjective injury were comparable between the two
      groups before starting treatment. RESULTS: The patients in the real low-level
      laser treatment group experienced a subjective improvement in both lip (p = 0.01)
      and chin (p = 0.02) after completion of the course of treatment. In addition,
      this group showed a significant decrease in the area of mechanoperception
      neurosensory deficit (p = 0.01) compared with no difference in the placebo group.
      The real low-level laser treatment group exhibited a strong tendency toward
      improvement in mechanoreceptor neurosensory deficit in the areas of most damage
      for both lip and chin. This improvement was especially pronounced in the lip
      region (p = 0.06). No similar tendency was demonstrated in the placebo group.
      Neither group showed any significant change or tendency to improvement in
      thermoception on completion of the course of treatment. CONCLUSION: In conclusion
      GaAlAs low-level laser treatment results in both a subjective and objective
      improvement in mechanical sensory perception in long-standing neurosensory
      deficit in the inferior alveolar nerve.

PMID- 8863302
TI  - Muscle attachment to the lateral aspect of the articular disk of the human
      temporomandibular joint.
AB  - OBJECTIVE: To investigate the anatomic attachments to the lateral aspect of the
      anterior band of the human temporomandibular joint articular disk. MATERIAL AND
      METHODS: Sixteen human cadaver half-heads were dissected and examined
      macroscopically. RESULTS: No direct attachment was observed between the deep
      masseter muscle and the temporomandibular joint articular disk. In one specimen,
      a small band of the anterior temporalis muscle was directly attached to the
      lateral aspect of the temporomandibular joint disk; whereas, on the same
      specimen, the attachment of the superior belly of the lateral pterygoid muscle
      was a comparatively large band. In another specimen, the lateral pterygoid muscle
      passed in an anterolateral direction. CONCLUSIONS: The masseter muscle has no
      functional significance in the biomechanics of temporomandibular joint disk
      displacement. The anterior temporalis muscle may have functional significance
      when it is accompanied by an anterolaterally divergent lateral pterygoid muscle.

PMID- 8863303
TI  - The assessment of trapezius muscle symptoms of patients with temporomandibular
      disorders by the use of liquid crystal thermography.
AB  - OBJECTIVE: To test the hypothesis that neuromuscular symptoms of patients with
      temporomandibular disorders that occur in the upper back and neck can be
      evaluated by recording the temperature patterns in the skin overlying the
      muscles. STUDY DESIGN: Liquid crystal contact thermography was evaluated on
      patients with temporomandibular disorders to demonstrate temperature changes in
      the muscles of the neck and upper back. The study consisted of 22 patients with
      temporomandibular disorders and 22 normal controls. RESULTS: The mean right
      versus-left-side temperature difference of the control group was 0.13 degree C
      whereas the patient group showed a difference of 0.78 degree C. Of the 22
      patients with temporomandibular disorders, 21 (95.5%) showed an increased
      temperature over the trapezius muscle on the symptomatic side. CONCLUSIONS: These
      findings indicate that thermography may be useful in the diagnosis of myofascial
      symptoms that may be associated with temporomandibular disorders.

PMID- 8863304
TI  - Biologic responses of the pulp to single-tooth dento-osseous osteotomy.
AB  - OBJECTIVE: This study was conducted to investigate biologic responses of the pulp
      to single-tooth dento-osseous osteotomy and to explore an appropriate level of
      transverse bone resection for maintaining biologic activity of the pulp in
      monkeys. STUDY DESIGN: The levels of transverse bone resection were designed at
      approximately 10 mm (10 mm group) and 5 mm (5 mm group) above the apices.
      Histologic and histomorphometric changes were evaluated microscopically, and
      changes in blood flow in the pulp were also measured in terms of vascular
      responses to a vasoconstrictor (noradrenaline, NA). RESULTS: Vacuolar
      degeneration in the pulp chamber associated with less number of the pulp cells
      were more prominent in the 5 mm group, and the response of blood flow to NA was
      maintained better in the 10-mm group. CONCLUSION: It is shown in this 8-week
      experiment that biologic activity of the pulp is much better preserved in the 10
      mm group than in the 5-mm group, whereas the pulpal response may become similar
      if observed for a longer period.

PMID- 8863305
TI  - Oral pathoses caused by Candida albicans during chemotherapy: update on
      development mechanisms.
AB  - Oral candidiasis occurs at a high frequency among immunocompromised hosts. The
      development mechanisms of oral pathoses associated with Candida are complex and
      certainly multifactorial. In immunocompromised patients, they include the
      evolution of the buccal flora associated with the influence of antineoplastic
      treatments and immunosuppression. They also include adherence of Candida to
      epithelial cells of the oral cavity as a function of host cell-related and yeast
      related factors. Interaction and cooperation between Candida and bacteria could
      be a third influence in the development of oral candidiasis. It seems important
      to determine these mechanisms more precisely so as to improve preventive and
      therapeutic measures.

PMID- 8863306
TI  - Cause of oral ulcers in HIV-infected patients: a study of 19 cases.
AB  - OBJECTIVES: To study the cause and clinical aspects of oral ulcers in HIV
      infected patients. STUDY DESIGN: Forty-one consecutive HIV-positive patients with
      long-standing oral ulcers were examined; 19 were evaluated by biopsy. From these
      19 cases, viral, bacterial, and fungal cultures and biopsies were taken in each
      patient. When indicated, special microbial stains were undertaken to identify
      bacteria or fungi. Ten cases without granulomatous bacterial fungal or
      lymphomatous features were available for in situ hybridization to detect viral
      DNA of herpes simplex virus 1 and 2, cytomegalovirus, varicella-zoster virus, and
      Epstein-Barr virus. RESULTS: Most of the oral ulcers occurred in patients with
      severe immunodepression. Median CD4 T-lymphocyte count was 60 cell/mm3 (range, 3
      to 335). It was ascertained that nine (47%) patients had nonspecific aphthous
      like ulcers, and ulcers caused by herpes group viruses were identified in six
      (31.5%) patients. One (5%) person was diagnosed with non-Hodgkin's lymphoma; and
      in one (5%) patient, multiple ulcers were an expression of lues maligna. Two
      ulcers (10.5%) in the palate harbored mycotic granulomatous foci (cryptococcosis,
      histoplasmosis). In this population, almost all of these ulcers were found to be
      large, persistent, and painful. CONCLUSIONS: Nontumefactive oral ulcers in HIV
      positive patients may be a source of diagnostic difficulties because of the
      diverse array of underlying pathologic entities and multiplicity of etiologic
      agents. Biopsy should always be performed on long-standing ulcers because either
      infection or a neoplastic process may be extant. In the absence of infection or
      neoplasm, such lesions are then designated as ulcers not otherwise specified.

PMID- 8863308
TI  - Computer expert system for the histopathologic diagnosis of salivary gland
      neoplasms.
AB  - The design, development, and testing of a prototype interactive histopathologic
      expert system capable of diagnosing 15 types of primary salivary gland neoplasms
      is described. The system incorporates a multiple subprogram modular design and
      makes use of multiple reasoning methods including: data-driven and goal-directed
      rule-based reasoning, linear pattern recognition, and Bayesian classification.
      Its user interface incorporates both a "hypertext" context-sensitive information
      assistance facility and the video display of stored and digitized
      photomicrographic images. The system can report a differential diagnosis of its
      findings with assessment of its confidence in its diagnosis. The system's
      performance was evaluated in a series of tests. The results of a weighted kappa
      analysis of the system's diagnoses versus those of four oral pathologists for 20
      salivary gland neoplasms indicated no statistical difference in diagnostic
      performance between the system and the human experts and each of the experts in
      relationship to the others (Wilcoxon rank sums test). A modified version of
      Turing's test of artificial intelligence demonstrated no statistically
      significant difference in the system's diagnoses versus the diagnosis of four
      human expert pathologists (Fisher's exact test). The knowledge and experience
      gained in the development and testing of the expert system described in this
      study have demonstrated the validity of histopathologic diagnostic expert systems
      in a selected area of oral pathology.

PMID- 8863307
TI  - Intraoral non-Hodgkin's lymphoma in seven patients with acquired immunodeficiency
      syndrome.
AB  - Since the appearance of AIDS, there has been a significant increase in the number
      of cases of oral non-Hodgkin's lymphoma. Rarely seen in the oral cavity before,
      non-Hodgkin's lymphoma is now seen with some frequency in HIV-positive patients.
      Oral HIV-related lymphomas exhibit an aggressive course and can mimic other oral
      tumors and infections, which makes early recognition and diagnosis important and
      difficult. We report on the clinical findings in seven homosexual men in whom the
      oral cavity was the first site in which non-Hodgkin's lymphoma appeared and the
      only site involved at the time of diagnosis. Treatment consisted of chemotherapy
      with or without radiation therapy. The relatively short survival in these
      patients averaged 8 months. All patients died of complications from their tumor.

PMID- 8863309
TI  - Cytogenetic analysis of salivary gland type tumors.
AB  - Fourteen salivary gland type tumors were analyzed with a combination of
      conventional cytogenetics via GTG-banding, molecular cytogenetics via fluorescent
      in situ hybridization, and chromosome morphometry. Nine tumors were benign (eight
      pleomorphic adenomas and one Warthin tumor) five tumors were malignant (one
      carcinoma ex pleomorphic adenoma, two adenoid cystic carcinomas including one
      from the breast, a basal cell adenocarcinoma, and an acinic cell carcinoma).
      Thirteen specimens grew in tissue culture; the basal cell adenocarcinoma did not
      grow. The Warthin tumor had a normal karyotype, one pleomorphic adenoma was
      normal, one had a clone with a missing Y chromosome, and the other pleomorphic
      adenomas had structural chromosomal abnormalities including the following:
      translocations between chromosomes 3 and 8, chromosomes 6 and 16, chromosomes 8
      and 9, chromosomes 8 and 12, chromosomes 8 and 14, and chromosomes 8 and 21. Of
      the four malignant tumors with karyotypes, the acinic cell carcinoma and one
      adenoid cystic carcinoma were normal, the second adenoid cystic carcinoma showed
      a normal polymorphic variant, whereas the carcinoma ex pleomorphic adenoma
      demonstrated the following karyotype: 46,XX,dir ins(8;5)(q12;q12q35),
      add(12)(p13)/46,XX. In conclusion, 66% of the benign tumors and 25% of the
      malignant tumors demonstrated abnormal karyotypes.

PMID- 8863310
TI  - Apocrine carcinoma of the lip: a case report including immunohistochemical and
      ultrastructural study, discussion of differential diagnosis, and review of the
      literature.
AB  - The light microscopic, immunohistochemical, and ultrastructural features of a
      case of apocrine carcinoma of the upper lip of a 54-year-old white man are
      described. The neoplasm had a cribriform intraductal component resembling
      apocrine carcinoma of the breast. The tumor had irregular borders and infiltrated
      skeletal muscle. The neoplastic cells had abundant eosinophilic granular
      cytoplasm and showed apical decapitation secretion characteristic of apocrine
      differentiation. The differential diagnosis is discussed with particular
      reference to distinction of the tumor from oncocytic carcinoma and ductal
      carcinoma of minor salivary gland.

PMID- 8863311
TI  - Sebaceous adenoma of the submandibular gland: a case report.

PMID- 8863312
TI  - Clinical management of nonhealing periradicular pathosis. Surgery versus
      endodontic retreatment.
AB  - OBJECTIVES: This prospective randomized study compared the outcome of retreatment
      and surgical intervention in root canal treated teeth with nonhealing
      periradicular pathosis. STUDY DESIGN: One such tooth from each of 38 patients was
      randomly allotted to retreatment or root-end resection and root-end filling.
      Treatment outcome after 1 year was evaluated and compared clinically and
      radiographically. RESULTS: The success rate for surgery was higher than for
      conventional retreatment, but the difference was not statistically significant.
      CONCLUSIONS: For management of nonhealing periradicular pathosis associated with
      root canal treated teeth, surgical intervention should be considered as an
      alternative to retreatment. In cases with a similar prognosis for both modes of
      treatment, the choice should be governed by consideration of intrinsic and
      extrinsic factors.

PMID- 8863313
TI  - Pathohistology of undecalcified primary teeth in vitamin D-resistant rickets:
      review and report of two cases.
AB  - The basic dental defects in vitamin D-resistant rickets seem to be manifested in
      dentin. Enamel is usually reported to be normal. This histologic examination
      showed the penetration of microorganisms through the calcified structures of the
      enamel layer without visible caries. The microorganisms passed through the
      dentinoenamel junction and invaded dentin, which was characterized by
      calcospherites and large amounts of interglobular dentin. Furthermore,
      microorganisms could be detected in dentinal tubules, which were exposed to the
      oral cavity when enamel was removed. However, large areas of tertiary dentin
      extended between such tubules and the pulp. These light microscopic results
      suggest that clinical manifestations, such as, pulp recrosis and periapical
      lesions (without carious defects) may be caused by the penetration of
      microorganisms through microclefts of the enamel layer as well as pathologically
      altered enamel microstructures of affected teeth.

PMID- 8863314
TI  - Oral complications associated with sickle cell anemia: a review and case report.
AB  - Sickle cell anemia is a multisystem disease that can affect the oral region. This
      article reviews previously reported oral complications associated with this
      disease and describes the cause of these problems. A case history describes a
      patient with multiple oral problems after a sickle cell crisis. The diagnostic
      and management problems of this case are highlighted. The need for a
      multidisciplinary approach to the care of these patients is emphasized.

PMID- 8863315
TI  - Magnetic resonance appearance of bone marrow in the mandible at different ages.
AB  - To differentiate pathologic states of bone marrow from normal age-related marrow
      conversion, magnetic resonance appearances of the mandible were analyzed cross
      sectionally according to age in 73 normal volunteers. Low signal intensities of
      red marrow first changed to high signal intensities in the anterior region of the
      mandibular body. With increase in age, marrow conversion was observed in the
      premolar/molar region, angle, ramus, and condyle regions in that order. No red
      marrow was recognized in the body of the mandible of subjects more than 30 years
      old. After the age of 30, the majority of the subjects showed high signal
      intensities in the entire bone marrow of the mandible. However, one subject over
      30 years of age showed some portions of red marrow in the ramus and condyle. This
      knowledge about age-related marrow conversion of the mandible on magnetic
      resonance imaging will be useful in the visual differentiation from abnormal bone
      marrow, such as anemias, inflammatory diseases, infiltrative neoplastic
      disorders, and metastatic diseases.

PMID- 8863316
TI  - "Those who cannot remember the past are condemned to repeat it'.

PMID- 8863317
TI  - Cervical spine injuries in children.
AB  - While cervical spine injuries are unusual in children, when they occur they
      frequently cause death or life-long disability. The primary care practitioner
      should be familiar with the signs and symptoms of cervical spine injuries, know
      the proper techniques of initial management, and engage in anticipatory guidance
      to prevent these injuries.

PMID- 8863318
TI  - Burn management in children.
AB  - Pediatric burn care consists of a coordinated program to provide acute
      physiological support during the shock phase, prompt wound closure, aggressive
      ancillary care, and appropriate postdischarge management. Adherence to
      predetermined burn care guidelines will produce the most optimal results in
      survival and return to function.

PMID- 8863319
TI  - Management of pediatric wounds.

PMID- 8863320
TI  - Pediatric abdominal surgical emergencies.
AB  - Pediatric abdominal surgical emergencies may present the primary physician with a
      diagnostic challenge. A systematic approach will help to minimize missed
      diagnoses and resultant complications. It always must be kept in mind that
      children often have atypical presentations of common entities. Prudent and
      directed use of laboratory and imaging studies will minimize misdiagnosis. The
      early involvement of surgical consultants in the care of pediatric patients who
      have significant abdominal symptoms or findings is always appropriate.

PMID- 8863321
TI  - Genitourinary surgical emergencies.

PMID- 8863322
TI  - Dialysis modality selection: harsh realities.

PMID- 8863323
TI  - In search of the ideal V.

PMID- 8863324
TI  - The rationale and ultimate limitations of urea kinetic modelling in the
      estimation of nutritional status.
AB  - OBJECTIVE: This paper reviews protein flux and amino acid metabolism and the
      potential inaccuracies inherent in using urea kinetics as an estimate of these
      processes, particularly in the patient undergoing peritoneal dialysis. The
      problems of extrapolating these estimates back to the whole patient are examined,
      addressing assumptions about neutral nitrogen balance, and the difficult issue of
      normalizing urea-derived indices to body size. CONCLUSIONS: Urea kinetics can be
      a helpful tool for assessing nutritional indices, but there are many caveats and
      many pitfalls that must be kept in mind to avoid being lulled into a false sense
      of confidence by the comfort of numbers.

PMID- 8863325
TI  - Nasal carriage and peritonitis by Staphylococcus aureus in patients on continuous
      ambulatory peritoneal dialysis: a prospective study.
AB  - OBJECTIVE: To establish whether or not patients on continuous ambulatory
      peritoneal dialysis (CAPD) using current infection control measures who are nasal
      carriers of Staphylococcus aureus are at risk for the development of S. aureus
      peritonitis. DESIGN: A prospective 22-month study analyzing nasal and skin/nasal
      (i.e., nasal and/or exit-site) carrier status for S. aureus and peritonitis
      episodes. Nasal swab cultures for S. aureus were taken with 1- to 3-month
      intervals; swab cultures from the catheter exit site were taken only when
      infection was suspected. SETTING: Renal unit, tertiary-care center. PATIENTS: All
      patients on CAPD at our center that could be observed during at least 2 months.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Nasal and skin/nasal carrier status,
      occurrence of peritonitis. RESULTS: Of 54 enrolled patients, 31 (57%) were nasal
      carriers for S. aureus: 6 of these 31 developed S. aureus peritonitis as opposed
      to none of 23 non-carriers (p = 0.03). The S. aureus peritonitis rate in 28
      skin/nasal carriers was increased when compared to non-carriers (p = 0.02), but
      there was no difference between chronic and intermittent skin/nasal carriers (p =
      0.63). CONCLUSIONS: In our population, nasal carriers are at increased risk for
      the development of S. aureusperitonitis. Further studies should evaluate the
      effect of eradication of nasal carriage of S. aureus and the effect of additional
      preventive hygienic measures on the occurrence of peritonitis by S. aureus.

PMID- 8863326
TI  - Neither size nor weight predicts survival in peritoneal dialysis patients.
AB  - OBJECTIVE: To determine if patient size or weight at the start of PD influences
      patient or technique survival. DESIGN: A prospective cohort study of adult PD
      patients. SETTING: A university and a Veterans Administration outpatient dialysis
      unit. PATIENTS: 343 adults patients with 660 years on PD enrolled from 1979 to
      1995. MAIN OUTCOME MEASURES: Patient survival (censoring for transplant, 60 days
      post-transfer to hemodialysis, and end of study) and technique survival
      (censoring for death, transplant, or end of the study) for patients as grouped by
      weight (< or = 64 kg vs. > 64 kg or < or = 82.7 kg vs. > 82.7 kg) or BSA (< or =
      2.0 m2 vs > 2.0 m2). RESULTS: Patient survival was 86.3% at one year, 77.0% at
      two years, 65.2% at three years, and 56.9% at 4 years. Technique survival was
      84.9% at one year, 77.5% at two years, 63.5% at three years, and 58.3% at four
      years. The patient and technique survival curves were not significantly different
      for patients as grouped by weight or BSA. Using Cox proportional hazards model,
      age, diabetes, peritonitis rate, and albumin at the start of PD were independent
      predictors of patient survival, but BSA and weight were not. The only predictor
      of technique survival was the peritonitis rate. Larger patients had higher
      initial albumins, which may indicate better nutritional status that may offset
      the risk of underdialysis. CONCLUSIONS: Large patients do as well as smaller
      patients on PD. Size alone should not preclude patients from PD.

PMID- 8863327
TI  - Epidemiologic and demographic aspects of peritoneal dialysis in Mexico.
AB  - OBJECTIVE: To assess some epidemiological and demographic aspects of peritoneal
      dialysis (PD) at the Instituto Mexicano del Seguro Social (IMSS), the major
      institution of social security in Mexico, that provides health care services for
      57% of the Mexican population at the time of the study. STUDY DESIGN: A cross
      sectional analysis of data about patients under peritoneal dialysis in 1992. DATA
      SOURCES: A national survey containing demographic data, dialysis modality, type
      of catheter, peritonitis and death rates, and questions on costs, medical staff,
      and physical facilities for PD in all of the hospitals of the IMSS. RESULTS: All
      hospitals returned the information requested. Intermittent peritoneal dialysis
      (IPD) was performed in 19 hospitals, continuous ambulatory peritoneal dialysis
      (CAPD) in 11, and both modalities in 90. In 61 hospitals, a special area was
      designed for PD; in the rest of them, beds from general internal medicine
      departments were used. All hospitals had a head for the PD programs; overall,
      teams had 240 physicians and 765 nurses for IPD, and 182 physicians and 313
      nurses for CAPD. CAPD prescription was four 2-L bags/day. For IPD, patients were
      hospitalized once a week and received 28 manually performed exchanges of 2-L
      bags; the mean time of hospitalization was 2.7 days, and 878 beds were used. The
      number of patients receiving PD was 7785, with a prevalence of 199.6 per million
      population. Of them, 4011 were on IPD and 3774 on CAPD; 54% of the patients were
      males. IPD patients' mean age was 49 +/- 17 yr, and that of CAPD patients' was 42
      +/- 17 yr (NS). Diabetic nephropathy was the most frequent cause of ESRD (44%).
      Infection was the most important complication detected. Rates of peritonitis were
      0.5/patient/yr on IPD and 0.8/patient/yr on CAPD. Annual mortality rates without
      stratification for specific causes were 34% in IPD and 17% in CAPD. Mortality
      rates may have been influenced by malnutrition and cardiovascular complications
      of diabetes, but specific causes of death were not investigated. All of the PD
      programs costs were covered by the institution. The cost per patient was not
      calculated, but IPD is known to be more expensive, due to its higher
      hospitalization rate. CONCLUSION: In spite of its higher cost and mortality, the
      institutions still use IPD, not so much on medical basis, but as the only
      alternative available for patients with adverse environmental, social,
      educational, and economic conditions for CAPD or HD.

PMID- 8863328
TI  - Variability in creatinine clearance (CCR) and KT/V due to different methods of
      calculating volume and CCR.
AB  - OBJECTIVE: This study aimed to compare the correlations between KT/V and
      creatinine clearance (Ccr) calculated by different methods and to determine and
      compare the correlations between KT/V and Ccr. DESIGN: Nonrandomized,
      retrospective analysis of data. SETTING: Continuous ambulatory peritoneal
      dialysis (CAPD) outpatient clinic in a teaching hospital. PATIENTS: All patients
      were included for analysis if the data collection was complete for the
      calculations of KT/V and Ccr using five different methods. INTERVENTIONS: Volume
      of distribution for urea (V) was estimated by four methods: Watson nomogram,
      ideal body weight (IBW), actual body weight, and total body surface area. Ccr was
      determined by five methods: Dialysate Ccr was calculated by creatinine (Cr)
      uncorrected and corrected for the presence of glucose; urinary Ccr was calculated
      using urinary Cr alone and the average urinary clearance of urea and Cr; and by
      the Cockcroft and Gault method. MAIN OUTCOME MEASURES: Correlations between KT/V
      and Ccr. RESULTS: Sixty-three data sets were collected from 52 CAPD patients. The
      correlations between weekly KT/V and Ccr normalized to 1.73 m2 body surface area
      were found to be highly variable from one method to another (r2 = 0.012 -0.494).
      For obese patients (20% above IBW), KT/V values obtained were more variable using
      the Watson nomogram compared to the IBW and BSA methods. CONCLUSION: KT/V
      calculated using the Watson nomogram and the Ccr determined using average of
      urinary urea and creatinine clearance gave the best correlation (r2 = 0.49).

PMID- 8863329
TI  - Low seroconversion with hepatitis B vaccination in peritoneal dialysis patients.
AB  - OBJECTIVE: To compare seroconversion using hepatitis B vaccine between
      hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: Data on PD
      patients vaccinated were collected retrospectively for the period 1992 to 1995.
      The data on HD patients were collected prospectively from 1991 to 1994. SETTING:
      A university outpatient dialysis center. PARTICIPANTS: All adult patients who
      received all four doses of hepatitis B vaccine while on dialysis were included
      (47 PD and 50 HD patients). INTERVENTION: Recombinant hepatitis B vaccine
      (Engerix), 40 micrograms IM was administered at 0, 1, 2, and 6 months. MAIN
      OUTCOME MEASURE: Seroconversion was measured after completion of the vaccination
      series. RESULTS: 74% of the HD patients seroconverted compared to 53% of PD
      patients (p = 0.03). Older, heavier patients compared to all the other patients
      had a lower seroconversion rate in both the HD patients (55% vs. 78 %) and PD
      patients (38% vs. 59%) (p = 0.03). CONCLUSION: The seroconversion rate to
      recombinant hepatitis B vaccine is lower in patients on PD than on HD for unclear
      reasons. Further studies are required to determine the etiology of this
      difference.

PMID- 8863330
TI  - Synthesis of hyaluronic acid by human peritoneal mesothelial cells: effect of
      cytokines and dialysate.
AB  - OBJECTIVE: To assess effects of the inflammatory cytokines (IL-1-beta, TNF-alpha,
      TGF-beta 1) and dialysate effluent on synthesis of hyaluronic acid by human
      peritoneal mesothelial cells (HMC) in in vitro culture. METHODS: Dialysate
      effluent was collected after the overnight dwell of Dianeal 1.5% from patients
      during CAPD training. HMC were obtained from omentum from nonuremic donors or
      were harvested from the dialysate effluent from CAPD patients. Synthesis of
      hyaluronic acid was studied on monolayers of HMC, which were deprived of serum 48
      hours prior to experiment. Effects of cytokines were tested in a medium with low
      serum concentration (0.1%) or in medium mixed (1:1 v/v) with the autologous
      dialysate. Hyaluronic acid level in medium was measured with radioimmunoassay.
      RESULTS: Cytokines enhanced synthesis of hyaluronic acid by HMC, and the
      strongest effect was induced by IL-1. Effluent dialysate stimulates synthesis of
      hyaluronic acid stronger than 10% FCS. Effluent dialysate and IL-1
      synergistically enhance synthesis of hyaluronic acid by HMC. CONCLUSION: Effluent
      dialysate from CAPD patients stimulates production of hyaluronic acid by HMC and
      acts synergistically with cytokines.

PMID- 8863331
TI  - Pharmacokinetics of once-daily IP gentamicin in CAPD patients.
AB  - OBJECTIVE: This study aimed to investigate the pharmacokinetic characteristics of
      once-daily intraperitoneal (IP) gentamicin in continuous ambulatory peritoneal
      dialysis (CAPD) patients. DESIGN: Prospective, nonrandomized, open study.
      SETTING: CAPD outpatient clinic in a teaching hospital. PATIENTS: Ten volunteer
      CAPD patients without peritonitis. INTERVENTIONS: Each patient received a single
      IP dose of 0.6 mg/kg of gentamicin. Blood and dialysate samples were collected at
      0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 hours after the administration of
      IP gentamicin. Any urine produced over the 24-hour study period was also
      collected. The dialysate concentration/time data were fitted to a monoexponential
      curve for all patients. RESULTS: The bioavailability was 56 +/- 11% over a six
      hour dwell. The mean serum elimination half-life (t1/2) was 35.8 hours. The
      volume of distribution was 0.23 +/- 0.08 L/kg. Equilibration of gentamicin across
      the peritoneal membrane was rapid, with a t1/2 equilibration of 4.5 hours. The
      peritoneal clearance was 5.74 +/- 1.5 mL/min. Patients-with residual renal
      function had significantly higher systemic gentamicin clearances (7.36 +/- 1.46
      mL/min) than those of anuric patients (4.76 +/- 1.08 mL/min, p < 0.024).
      CONCLUSION: Currently recommended doses of once-daily IP gentamicin for the
      treatment of peritonitis may not produce the desired therapeutic serum and
      dialysate concentrations over 24 hours for effective treatment of peritonitis.

PMID- 8863332
TI  - Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a
      CAPD peritonitis.
AB  - OBJECTIVE: To investigate whether or not a change in dialysate interleukin-8 (IL
      8) concentration precedes the onset of clinically overt peritonitis and is
      significant in the recruitment of granulocytes during continuous ambulatory
      peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients stored
      their overnight effluent at 4 degrees C, which was routinely thrown away after 2
      days. If peritonitis developed, patients delivered their effluent of the
      preceding two nights and the peritonitis effluent for analysis. A control study
      was performed 1 to 3 months after recovery. Dialysate samples were analyzed for
      number of cells, differential cell count, IL-8 and elastase concentrations, and
      their neutrophil chemoattractive capacity. In addition, serum samples during
      peritonitis were analyzed for IL-8 concentrations. RESULTS: Ten peritonitis
      episodes in 7 patients were analyzed. Numbers of neutrophils and levels of
      dialysate IL-8 and elastase started to increase 4 to 12 hours before the first
      peritonitis effluent. The dialysate/serum IL-8 ratio was 423.5 during peritonitis
      and 7.0 in the postperitonitis controls. There was a significant correlation
      between the number of neutrophils and IL-8 concentration in the dialysate. The in
      vitro neutrophil chemotaxis was increased toward the peritonitis effluents, as
      compared to control effluents. Incubation of the peritonitis effluents with anti
      IL-8 monoclonal antibody blocked the increase in neutrophil chemotaxis above
      control levels by an average of 26.7%. CONCLUSION: IL-8 is produced in the
      peritoneal cavity during CAPD treatment and may mediate part of the neutrophil
      recruitment and degranulation in the initial phase of a CAPD peritonitis.

PMID- 8863333
TI  - Peritoneal mesothelium in vitro: an electrophysiologic study.
AB  - OBJECTIVE: In vitro electrophysiologic characterization of the peritoneal
      mesothelium as a barrier for ion transport during peritoneal dialysis. DESIGN:
      Experiments were performed on rat's mesentery and diaphragm. Electrophysiologic
      parameters of the isolated tissue were assessed in the modified Ussing system.
      RESULTS: We have shown that there are significant differences between
      electrophysiological parameters of the parietal and visceral peritoneum. The
      value of the potential difference across the parietal mesothelium lining the
      abdominal part of the diaphragm (PDmpt) was 0.26 +/- 0.03 mV (mean +/- SEM), with
      a positive charge recorded from the apical side of the mesothelium. Electrical
      resistance of the mesothelial monolayer (Rmpt) was Rmpt = 13.6 +/- 1.3 omega.cm2
      and 1.4 +/- 0.2 omega.cm2 for the tissue isolated from the diaphragm and
      mesentery, respectively. Both the mechanical and chemical procedures used for the
      preparation of the peritoneal membrane model from the diaphragm have been shown
      to produce similar values of electrophysiological parameters. CONCLUSION: The
      electrophysiologic approach presented here may be a useful tool for studies of
      highly permeable biological membranes such as the peritoneal mesothelium. The
      mesothelial tissue isolated from the rat diaphragm has been shown to be a
      suitable model for electrophysiologic studies of the peritoneum as assessed by
      the values of the PDmpt and Rmpt parameters.

PMID- 8863335
TI  - Differential glucocorticoid responsiveness of dialysis patients' lymphocytes.
AB  - OBJECTIVES: To evaluate in vitro glucocorticoid responsiveness of
      phytohemagglutinin (PHA)-stimulated lymphocytes from peritoneal dialysis (PD)
      patients compared to hemodialysis (HD) patients. DESIGN: Cross-sectional study of
      prevalent PD and HD patients and concurrent control subjects. SETTING: Urban
      outpatient dialysis unit. PATIENTS: 20 HD, 14 PD, and 20 control subjects.
      MEASUREMENTS: Using standard lymphocyte culture techniques, the concentration of
      prednisolone (P) and methylprednisolone (MP) required to cause 50% inhibition
      (IC50) of the proliferative response to phytohemagglutinin (PHA) was determined
      from dose-response curves. RESULTS: There was considerable heterogeneity in the
      sensitivities of individual patients' PBMC to glucocorticoid inhibition,
      especially those of HD patients' cells to P. The mean +/- SD IC50 for MP was
      significantly (p < or = 0.001) lower than that for P in each cohort: PD 11 +/- 5
      vs. 34 +/- 18 ng/mL; HD 22 +/- 14 vs. 89 +/- 43 ng/mL; control subjects 14 +/- 11
      vs. 55 +/- 56 ng/mL. Interestingly, the IC50 for both P and MP was significantly
      higher in HD than in either PD or controls (ANOVA, P: F = 6.56, p = 0.003; MP: F
      = 3.77, p = 0.03), indicating decreased sensitivity of HD lymphocytes to both
      drugs. There were no significant differences in mean IC50 values for either P or
      MP between PD and controls. No correlations were found between IC50 for either P
      or MP and patient age, gender, duration of dialysis, serum creatinine, serum
      albumin, or parathyroid hormone level. CONCLUSIONS: In vitro glucocorticoid
      responsiveness of dialysis patients' lymphocytes appears to be influenced by
      dialysis modality, but the factor(s) involved remains to be determined. The
      greater sensitivity of PD lymphocytes to both P and MP might result in better
      immunosuppression and less severe rejection after renal transplantation. MP may
      be particularly advantageous following renal transplantation for any patient
      manifesting relative or absolute in vitro resistance to P.

PMID- 8863334
TI  - Biocompatibility of silver-coated peritoneal dialysis catheter in a porcine
      model.
AB  - OBJECTIVE: Previous studies have shown that silver formulations coated onto
      implantable materials retard bacterial colonization and reduce the incidence of
      catheter-related infections. The objective of this study was to assess the
      histologic effects of sputter-coated silver/ silicone implants on host tissue.
      DESIGN: Sputter silver-coated silicone peritoneal dialysis catheter segments with
      and without Dacron cuffs were implanted in the subcutaneous fat and muscle in 4
      pigs. Noncoated implants served as controls. The specimens were retrieved at 1,
      2, 3, 4, 7, 8, 9, 10, 12, and 27 weeks. EXPERIMENTAL ANIMALS: Four 6-week-old
      male Yorkshire-Landrace pigs (5-6 kg) were used. MAIN OUTCOME MEASURES:
      Histologic parameters evaluated included the degree of inflammation, the number
      of giant cells, the extent of silver particulate inclusions, and the thickness of
      the capsules. All specimens were evaluated by a single blinded pathologist.
      Microbiologic analyses were also performed. RESULTS: The silver-coated catheters
      were associated with less inflammation than were the noncoated catheters, both in
      fat and muscle (p = 0.04). The number of giant cells was also lower around the
      silver-coated than the non-coated catheters, which were implanted in subcutaneous
      fat (p < 0.05). Particulate inclusions compatible with silver or silver oxide
      were observed only in tissue around silver-coated implants (p < 0.0001). The
      thickness of the capsules and the extent of the inflammatory zones were not
      significantly different. There was no evidence of infection-related changes.
      CONCLUSIONS: These data suggest that the sputter silver coating does not act as a
      significant tissue irritant.

PMID- 8863336
TI  - Microcirculation of the fingernail fold in CAPD patients: preliminary
      observations.
AB  - OBJECTIVE: To study changes in the peritoneal microcirculation during continuous
      ambulatory peritoneal dialysis (CAPD) by studying change in the microcirculation
      of the fingernails of CAPD patients. SETTING: A university department. DESIGN: A
      cross-sectional study of 10 nondiabetic patients on CAPD. INTERVENTION:
      Hemorrheological tests of fingernail microcirculation using equipment built at
      our university. MAIN OUTCOME MEASURES: Microcirculation was characterized by
      estimation of capillary density, red blood cell (RBC) column diameter, torque
      index, and RBC flow velocity semiquantitatively using videocapillaroscopy at the
      fingernail fold and plasma viscosimetry. Findings were correlated with treatment
      duration, peritoneal clearance, state of capillary morphology and hemodynamics,
      and lipid and fibrinogen levels. RESULTS: Treatment duration was significantly
      correlated (p < or = 0.05) with low-density lipoprotein (LDL) (r = 0.776) and
      clearances of urea (r = -0.583), uric acid (r = -0.666), and potassium (r = 
      0.764). Changes in capillary morphology were correlated to clearances of urea (r
      = 0.643) and uric acid (r = 0.701). The fibrinogen concentration increases plasma
      viscosity (r = 0.799) and deteriorates the capillary state (r = -0.706). In
      addition, plasma viscosity correlates to cholesterol (r = 0.620, NS) and LDL (r =
      0.781), but not to high-density lipoprotein and triglycerides. CONCLUSION: CAPD
      treatment results in lipid abnormalities and high fibrinogen levels that may
      cause microvascular damage and poor perfusion. These interactions may explain the
      deterioration of peritoneal transport in some CAPD patients.

PMID- 8863337
TI  - Hyporesponsiveness to erythropoietin: overview, 1996.

PMID- 8863338
TI  - Thoracoscopic pleurodesis for massive hydrothorax complicating CAPD.

PMID- 8863339
TI  - Acute treatment of constipation may lead to transmural migration of bacteria
      resulting in gram-negative, polymicrobial, or fungal peritonitis.

PMID- 8863340
TI  - Creatinine clearance in amputees on CPD: body surface area calculations.

PMID- 8863341
TI  - Diagnostic difficulties with mycobacteria peritonitis in a CAPD patient.

PMID- 8863342
TI  - Mechanisms of signal-mediated protein sorting in the endocytic and secretory
      pathways.
AB  - The ability to sort proteins to different intracellular compartments is an
      essential property of all cells. Many diseases are caused by a failure of certain
      proteins to be sorted properly in the endocytic and secretory pathways. In
      addition, various intracellular pathogens use their hosts' protein-sorting
      machinery at different stages of their life cycles. These facts underscore the
      importance of understanding the mechanisms of protein sorting at a molecular
      level. In this article, we review recent advances in the identification of
      signals that direct proteins to their correct intracellular locations and of the
      recognition molecules that bind to the signals. The implications of these
      findings for the trafficking of various proteins are discussed.

PMID- 8863343
TI  - Cushing's disease preceded by generalized glucocorticoid resistance: clinical
      consequences of a novel, dominant-negative glucocorticoid receptor mutation.
AB  - Generalized glucocorticoid resistance is associated with chronic hyperactivation
      of the hypothalamic-pituitary-adrenal axis, compensating for impaired
      glucocorticoid receptor function. We report a unique patient with sporadic
      generalized glucocorticoid resistance who, at age 33, presented with infertility
      and hypertension and, at 38, developed pituitary Cushing's disease. Leukocyte
      binding studies revealed normal affinity of the glucocorticoid receptor but a
      reduction of binding sites by 50%. [3H]thymidine incorporation by this patient's
      lymphocytes was not suppressible by dexamethasone. He had a novel heterozygous
      missense mutation in the glucocorticoid receptor gene (isoleucine 559 to
      asparagine 559). The mutant receptor exhibited a strong dominant-negative effect
      on the ability of the wild-type receptor to induce gene transcription in vitro.
      The mutation was present in all of the patient's cultured lymphoblasts and
      fibroblasts as well as in 50% of his sperm, as demonstrated by single-cell
      polymerase chain reaction; it was not present in his parents and seven siblings.
      This novel mutation was thus both de novo and present in the germ line.
      Immunohistochemical staining of this patient's pituitary corticotropinoma
      revealed accumulation of p53 protein, indicating the presence of a putative
      somatic oncogenic mutation in the p53 gene in the tumor cells. Investigation of
      the lymphoblast and skin fibroblast cultures for p53 abnormalities did not show
      any aberration. Thus, a novel de novo germ line mutation of the glucocorticoid
      receptor with strong dominant-negative activity caused severe sporadic
      generalized glucocorticoid resistance, which preceded corticotroph adenoma
      formation. The latter probably was due to the combined effects of chronic
      corticotroph hyperstimulation, decreased glucocorticoid negative feedback, and at
      least one subsequent somatic defect in the control of the cell cycle.

PMID- 8863344
TI  - A case of Becker muscular dystrophy resulting from the skipping of four
      contiguous exons (71-74) of the dystrophin gene during mRNA maturation.
AB  - The mutations in one-third of both Duchenne and Becker muscular dystrophy
      patients remain unknown because they do not involve gross rearrangements of the
      dystrophin gene. Here we report the first example of multiple exon skipping
      during the splicing of dystrophin mRNA precursor encoded by an apparently normal
      dystrophin gene. A 9-year-old Japanese boy exhibiting excessive fatigue and high
      serum creatine kinase activity was examined for dystrophinopathy. An
      immunohistochemical study of muscle tissue biopsy disclosed faint and
      discontinuous staining of the N-terminal and rod domains of dystrophin but no
      staining at all of the C-terminal domain of dystrophin. The dystrophin transcript
      from muscle tissue was analyzed by the reverse transcriptase polymerase chain
      reaction. An amplified product encompassing exons 67-79 of dystrophin cDNA was
      found to be smaller than that of the wild-type product. Sequence analysis of this
      fragment showed that the 3' end of exon 70 was directly connected to the 5' end
      of exon 75 and, thus, that exons 71-74 were completely absent. As a result, a
      truncated dystrophin protein lacking 110 amino acids from the C-terminal domain
      should result from translation of this truncated mRNA, and the patient was
      diagnosed as having Becker muscular dystrophy at the molecular level. Genomic DNA
      was analyzed to identify the cause of the disappearance of these exons. Every
      exon-encompassing region could be amplified from genomic DNA, indicating that the
      dystrophin gene is intact. Furthermore, sequencing of these amplified products
      did not disclose any particular nucleotide change that could be responsible for
      the multiple exon skipping observed. Considering that exons 71-74 are spliced out
      alternatively in some tissue-specific isoforms, to suppose that the alternative
      splicing machinery is present in the muscle tissue of the index case and that it
      is activated by an undetermined mechanism is reasonable. These results illustrate
      a novel genetic anomaly that results in dystrophinopathy.

PMID- 8863345
TI  - A contaminant of L-tryptophan enhances expression of dermal collagen in a murine
      model of eosinophilia myalgia syndrome.
AB  - The eosinophilia-myalgia syndrome was associated with the ingestion of L
      tryptophan products containing a number of contaminants, one of which has been
      identified as 1,1'-ethylidene-bis-(L-tryptophan) (EBT), also known as peak E or
      peak 97. In earlier studies, we demonstrated that EBT induces inflammation and
      fibrosis in dermal and subcutaneous tissue of C57BL/6 mice. Others have shown EBT
      to be a potent stimulus for fibroblast activation and collagen synthesis in
      vitro, and dermal tissue from EMS patients reveals evidence of enhanced collagen
      gene expression. In the present study using Northern blot analysis and in situ
      hybridization, we demonstrate enhanced expression of genes for types I, III, and
      VI collagen in the dermis and subcutis of C57BL/6 mice treated with EBT for 3-21
      days. Increased type I procollagen mRNA was noted on day 6 of EBT treatment and
      was followed by enhanced expression of type III and VI procollagen mRNA at day
      21. L-Tryptophan, free of contaminants associated with the eosinophilia-myalgia
      syndrome epidemic, increased dermal collagen mRNA to a lesser extent than did
      EBT. Increased procollagen gene expression was accompanied by evidence of
      enhanced TGF-beta 1 expression in the dermis and subcutis. This animal model
      provides additional evidence for EBT as a causal agent of the eosinophilia
      myalgia syndrome and should prove useful in the study of the pathogenesis of that
      syndrome.

PMID- 8863346
TI  - Influence of the rheumatoid arthritis-associated shared epitope on T-cell
      receptor repertoire formation.
AB  - Rheumatoid arthritis is associated with several human leukocyte antigen DRB1
      types that express a common five-amino acid sequence called the shared epitope.
      Here we show that the human leukocyte antigen DRB1 shared epitope expands naive T
      lymphocytes that express the same T-cell-receptor variable region-joining region
      combinations that are prevalent in the synovia of rheumatoid arthritis patients.
      Thus, the shared epitope could affect rheumatoid arthritis disease susceptibility
      by selecting in the premorbid state specific T-cell subsets that contribute to
      synovial inflammation.

PMID- 8863347
TI  - Subunit composition of AMPD varies in response to changes in AMPD1 and AMPD3 gene
      expression in skeletal muscle.
AB  - Adenosine monophosphate deaminase (AMPD), a central enzyme in energy metabolism
      in skeletal muscle, is encoded by a multigene family in higher eukaryotes.
      Denervation was used as a stimulus to induce a change in fiber type composition
      of rat gastrocnemius muscle and, consequently, gene expression. Specific antisera
      and nucleic acid probes were used to assess changes in expression of the AMPD1
      and AMPD3 genes. Total AMPD activity in denervated skeletal muscle increased by
      34%. The composition of the AMPD tetrameric holoenzyme was altered in two ways:
      The percentage of AMPD holoenzyme molecules consisting of one or more AMPD3
      subunits increased three-fold, and the percentage of AMPD1 mRNA that excludes
      exon 2-encoded sequences doubled. These results suggest that expression of the
      AMPD1 and AMPD3 genes may be coordinated in myocytes to effect production of an
      AMPD holoenzyme of varying subunit composition.

PMID- 8863348
TI  - Regulation of alpha 2A-adrenergic receptor expression in the human colon
      carcinoma cell line HT29: SCFA-induced enterocytic differentiation results in an
      inhibition of alpha 2C10 gene transcription.
AB  - Previous studies on the intestinal epithelium from various species have shown
      that the number of alpha 2-adrenergic receptors in immature cells from the crypts
      is several-fold higher than in mature cells from the villi, thus suggesting an
      inverse relationship between enterocytic differentiation and the expression of
      this inhibitory receptor. The receptor density along the surface-crypt axis of
      the human colonic mucosa is correlated with the amount of alpha 2C10 mRNA;
      however, the mechanisms underlying this regulation remain unknown. The human
      colonic adenocarcinoma cell line HT29, which expresses the alpha 2A-adrenergic
      receptor and is able to undergo enterocytic differentiation, is a suitable model
      with which to investigate this question in vitro. In this study, we explored the
      effects of short chain fatty acids (SCFAs), differentiating agents normally
      present in the colon lumen, on alpha 2-adrenergic receptor expression. Exposure
      of HT29 cells to butyrate and propionate, but not acetate, resulted in a large
      diminution of [3H]RX821002 binding sites. The reduction of alpha 2-adrenergic
      receptor number induced by butyrate or propionate was due to decreased amounts of
      alpha 2C10 mRNA and was associated with an increase of alkaline phosphatase
      activity, which reflected the emergence of a more differentiated phenotype. The
      changes in alpha 2C10 mRNA level induced by both SCFAs were dose-dependent,
      rapid, and reversible and resulted from a diminution in the transcription rate of
      the alpha 2C10 gene. Finally, these effects were mimicked by trichostatin A,
      indicating that they are triggered primarily through inhibition of histone
      deacetylases. The present findings demonstrate that decrease of alpha 2
      adrenergic receptor expression is a very early event of the HT29 cell
      differentiation process. They also suggest that SCFAs, which originate from
      bacterial fermentation of dietary fibers, may play a role in the regulation of
      the alpha 2-adrenergic receptivity of colonic mucosa in vivo.

PMID- 8863350
TI  - The spectrum of African Kaposi's sarcoma: is it consequential upon diverse
      immunological responses?
AB  - Kaposi's sarcoma (KS) is a complex, multicellular growth, the pathogenesis of
      which remains unclear. Endemic African Kaposi's Sarcoma (KS) is characterized by
      its epidemiological peculiarities, protean clinical manifestations and an
      unpredictable natural history. A wide spectrum of clinical manifestations occurs,
      although the reasons for the heterogeneity remain unclear. Clinical observations
      in the presentation of human immunodeficiency virus (HIV)-associated epidemic
      African KS show a considerable overlap with endemic African KS obscuring the
      conventional binomial concept of African KS which was developed in light of the
      HIV epidemic. It is probable that once the KS lesions are expressed clinically,
      the subsequent spectrum and behaviour of all forms of African KS are
      consequential upon a complex interplay between the nature of the host cell
      mediated immune responses and the putative aetiological factor(s).

PMID- 8863349
TI  - A 10-year follow-up study of tick-borne encephalitis in the Stockholm area and a
      review of the literature: need for a vaccination strategy.
AB  - 143 people treated for tick-borne encephalitis (TBE) were included in a
      retrospective follow-up study. Sequelae and epidemiological characteristics in
      114 individuals were analysed. The case fatality rate and the prevalence of
      residual paresis were low, 1.4 and 2.7%, respectively. However, 40 (35.7%)
      individuals were found to have a postencephalitic syndrome after a median follow
      up time of 47 months, and a majority (77.5%) of these were classified as moderate
      to severe. Various mental disorders, balance and co-ordination disorders and
      headache were the most frequently reported symptoms. Increasing age was
      correlated to a longer duration of hospital stay, longer convalescence and
      increased risk of permanent sequelae. Results from a neuropsychiatric
      questionnaire showed marked differences between the subjects with sequelae
      compared to controls. 57% had noticed a tick bite before admission, and 48% were
      aware of at least one person in their environment who previously had contracted
      TBE. 79% were permanent residents or visited endemic areas often and regularly.
      In conclusion, we have found that TBE in the Stockholm area has a low case
      fatality rate, but gives rise to a considerable number of different neurological
      and mental sequelae, which justifies vaccination of a defined risk population in
      endemic areas.

PMID- 8863351
TI  - Mad cow disease and Creutzfeldt-Jakob disease--is there a link?
AB  - The report of the Creutzfeldt-Jakob Surveillance Unit from March 1996 regarding
      10 cases of a new variant of Creutzfeldt-Jakob disease (CJD) in young adults
      caused a great deal of uproar when it was suggested that a possible link with
      bovine spongiform encephalopathy (BSE) could not be excluded. BSE was first
      noticed in 1986 after the introduction of modified rendering systems in the
      manufacture of meat and bone meal containing animal wastes contaminated with
      scraple-like agents. This article reviews available information on CJD, BSE and
      other diseases caused by prions, transmission studies and the report of the CJD
      Surveillance Unit and discusses possible links between BSE and the new variant of
      CJD.

PMID- 8863352
TI  - An outbreak of mumps in a population partially vaccinated with the Rubini strain.
AB  - Since 1991, 6 years after the recommendation of universal childhood triple
      vaccination against measles, mumps and rubella (M + M + R), Switzerland has been
      confronted with an increasing number of mumps cases affecting both vaccinated and
      unvaccinated children. The M + M + R vaccine mainly used in the Swiss population
      after 1986 contains the highly attenuated Rubini strain of mumps virus. We
      analysed an outbreak of 102 suspected mumps cases by virus isolation,
      determination of IgM antibodies to mumps virus in 27 acute phase sera, and
      verification of vaccination histories. Mumps was confirmed by virus isolation in
      88 patients, of whom 72 had previously received the Rubini vaccine strain. IgM
      antibodies to mumps virus were detected in 24/27 acute phase serum samples. A
      group of 92 subjects from the same geographic area without signs of mumps virus
      infection served as controls. IgG antibodies to mumps virus and vaccination
      status were assessed in these children. The vaccination rate in these controls
      was 61%, with equal seropositivity for unvaccinated and Rubini-vaccinated
      subjects. These data support other recent reports which indicate an insufficient
      protective efficacy of current mumps vaccines.

PMID- 8863353
TI  - Assessments of plasma HIV RNA and CD4 cell counts after combined Pneumovax and
      tetanus toxoid vaccination: no detectable increase in HIV replication 6 weeks
      after immunization.
AB  - The influence of simultaneous vaccination with Pneumovax and tetanus toxoid on
      plasma human immunodeficiency virus (HIV) RNA and CD4 cell counts was assessed in
      patients with HIV infection. Six weeks after immunization plasma HIV RNA did not
      differ significantly from baseline values. A slight decline in CD4 cell counts
      after vaccination was detected. There was no correlation between the serological
      responses to pneumococcal vaccination and baseline CD4 cell counts, changes in
      HIV RNA or CD4 cell counts. In conclusion, immunization did not induce an
      increase in viral replication detectable 6 weeks after immunization.

PMID- 8863354
TI  - Transmission of genital human papillomavirus infections is unlikely through the
      floor and seats of humid dwellings in countries of high-level hygiene.
AB  - To evaluate the transmission of genital human papillomavirus (HPV) through the
      floor and seats of humid dwellings, samples were collected with a toothbrush from
      the floor and seat surfaces of humid dwellings; showers, saunas and dressing
      rooms. The survey included 3 bathing resorts, 1 indoor swimming pool, 2 schools
      and 2 private homes. Polymerase chain reaction (PCR) was used to amplify the
      human beta-globin gene and HPV DNA. The results for HPV DNA amplification were
      confirmed by Southern blot hybridization under low stringency using a probe
      mixture of HPV types 6, 16, 18 and 31. beta-globin could be amplified only from 3
      sample taken from a dressing room of and indoor public swimming pool. No HPV DNA
      positive samples were found. These results indicate that transmission of genital
      HPV infection via floor or seat surfaces in the above dwellings in general or
      family use is highly unlikely.

PMID- 8863356
TI  - Meningococcal disease in Norway 1992-1995. Epidemiology and fatality.
AB  - We analysed data on all cases of meningococcal disease (MCD) reported to the
      Norwegian Notification System for Infectious Diseases during the period 1992
      1995. For 1994, additional information on fatalities was gathered. Notifications
      were received from laboratories and clinicians. A total of 586 patients were
      included. The incidence decreased from 4.6 per 100000 in 1992 to 2.4 in 1994, and
      then rose to 3.7 in 1995. The initial decrease, a trend also observed in previous
      years, was seen in both main serogroups B and C. This decline was broken with the
      increase of serogroup B in 1995. MCD predominantly affects children below 5 years
      and teenagers. In 1994, 17/105 (16%) patients died. Main risk factors for fatal
      outcome were age above 30 years (adjusted odds ratio (OR) 19.8; 95% confidence
      interval (CI) 2.4-164), septicaemia (adjusted OR 9.5; 95% CI 2.2-41) and disease
      caused by strains B:15 (adjusted OR 6.4; 95% CI 1.2-35) or C:2a (adjusted OR
      10.1; 95% CI 1.6-62). We conclude that the incidence of MCD in Norway is
      unpredictable and that the case fatality rate is substantially higher than
      previously believed.

PMID- 8863355
TI  - Incidence and prognosis of meningitis due to Haemophilus influenzae,
      Streptococcus pneumoniae and Neisseria meningitidis in Sweden.
AB  - The incidence, concomitant conditions and case fatality rate of Haemophilus
      influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal
      infections were studied retrospectively in Sweden (population 8.4 million) for
      the years 1987-89, the period before vaccination against Hi type b started. A
      total of 1,019 cases with culture-verified infection were found. The incidence
      rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal
      meningitis and 1.0 for invasive meningococcal infections. The age-specific
      incidence was highest in the 3-23 months age group for the 3 bacterial species.
      Pneumococcal meningitis was common in individuals > or = 60 years and
      meningococcal infections in the age-group 10-24 years. A serious concomitant
      condition was known in 57% of all patients with pneumococcal meningitis while
      this was uncommon for the other organisms. The case fatality rate was 2% for Hi
      meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections.
      All 81 pneumococcal isolates which had been serotyped belonged to serotypes in
      the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged
      to serogroup B. In conclusion, the high incidence of Hib meningitis justifies
      general Hib vaccination. Development of a vaccine against N. meningitidis group B
      should have high priority. Furthermore, improved pneumococcal vaccines are needed
      for patients with predisposing conditions. The currently available pneumococcal
      polysaccharide vaccine seems to be underused.

PMID- 8863357
TI  - Incidence, aetiology, and prognosis of acute epiglottitis in children and adults
      in Sweden.
AB  - A retrospective study of the incidence, aetiology and case fatality rate of acute
      epiglottitis in children and adults was performed. The study covered the whole of
      Sweden (population 8.4 million) during the years 1987-89, before general
      vaccination against Haemophilus influenzae (Hi) type b was started. Patients were
      included if it was documented that they fulfilled all 3 of the following
      criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b)
      inspiratory stridor or difficulties in swallowing, and (c) a temperature > or =
      38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults
      (> or = 20 years) were found. The age-specific incidence was highest in children
      aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per
      year. In the age group 0-19 years, blood cultures had been obtained from 195
      (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298
      blood cultures yielded Hi, while pneumococci were isolated from 5 and group A
      streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%)
      needed an artificial airway. Five children and 12 adults died. In conclusion, the
      incidence of acute epiglottis in Sweden is very high. Compared to a previous
      country-wide study covering the years 1981-83 that used the same methods for case
      finding and case definition, the incidence in children had decreased while the
      incidence in adults had increased.

PMID- 8863358
TI  - Invasive Haemophilus influenzae disease and epiglottitis among Swiss children
      from 1980 to 1993: evidence for herd immunity among older age groups. The Swiss
      Haemophilus Influenzae Study Group.
AB  - We analysed time trends in the incidence of invasive Haemophilus influenzae
      disease in Switzerland between 1980 and 1993 to investigate whether conjugated H.
      influenzae type b vaccines, licensed in Switzerland in May 1990, confer indirect
      protection to children in older, non-vaccinated age groups. Data were obtained
      from the records of 39 Swiss paediatric clinics for 2,857 children 0-16 years old
      with invasive H. influenzae disease. Incidence time trends were analysed by
      Poisson regression. The diseases incidence decreased by 80% among 0-4-year-old
      children (i.e. those eligible for vaccination) between 1990 and 1993. Among
      children aged 5-16 years, there also was an abrupt 50% fall in the incidence of
      H. influenzae meningitis after 1990. However, the incidence of epiglottitis in
      this age group had started to decline before conjugated vaccines became
      available, with no additional decline thereafter. While our results suggest some
      indirect protection conferred to older, non-vaccinated children through the
      administration of conjugated vaccines to younger children, they also argue that
      underlying time trends of invasive H. influenzae disease need not be considered
      when interpreting incidence rates in the vaccine era.

PMID- 8863359
TI  - Epidemiologic application of pulsed-field gel electrophoresis to an outbreak of
      Campylobacter fetus meningitis in a neonatal intensive care unit.
AB  - An outbreak of nosocomial Campylobacter fetus meningitis occurred in a neonatal
      intensive care unit (NICU). Eight C. fetus strains were isolated from 4 infants
      with meningitis, the mother of the index patient and 2 infants who were
      asymptomatic intestinal carriers. The pulsed-field gel electrophoresis (PFGE)
      pattern with the restriction endonucleases Smal and Sall were found to be
      identical for the nosocomial C. fetus isolates, but the patterns were different
      from those of sporadic strains. These nosocomial strains were strongly suspected
      to be a single strain. The finding revealed that the index patient was infected
      by the mother, and that the outbreak developed from this patient by cross
      infection. This is the first confirmed nosocomial C. fetus meningitis outbreak
      spread by cross-infection in a NICU.

PMID- 8863360
TI  - Persistent Chlamydia pneumoniae infection in a Swedish family.
AB  - Chlamydia pneumoniae, an etiological agent for respiratory tract infection, was
      found as a cause of persistent infection in a family group. During the
      observation period of 2 1/2 years, serology and polymerase chain reaction for C.
      pneumoniae demonstrated a failure to eradicate the organism, despite several
      prolonged courses of antibiotics known to be effective against chlamydia species.

PMID- 8863361
TI  - Detection and identification of non-tuberculous mycobacterial infections in 6,472
      tuberculosis suspected patients.
AB  - Between March 1993 and March 1994, 82 patients with infection by non-tuberculous
      mycobacteria (NTM) and 443 patients with tuberculosis (TB) were registered among
      6,472 patients with suspected tuberculosis. Skin-test reactivity to purified
      protein derivative (PPD) in patients demonstrated indurations of 10-14 mm or more
      for the majority of patients in both groups. Most patients with NTM infection had
      abnormal chest roentgenograms showing sporadic infiltrations, nodular abscesses,
      and cavities resembling TB radiological evidence. The similarity in age range,
      PPD skin reaction, and radiological evidence in patients infected with NTM or
      Mycobacterium tuberculosis (MTB) can mislead the physician. Some NTM species were
      recovered more often than others. Mycobacterium fortuitum from 22 clinical
      specimens (26.8%); Mycobacterium gastric 19 (23.1%); and Mycobacterium terrae
      complex 15 (18.3%). The antimicrobial drug susceptibility tests of the isolated
      organisms showed that 42 (9.5%) isolates of MTB were resistant to isoniazid and
      31 (7.0%) to streptomycin. a few strains (1.3%) were identified as being
      resistant to a combination of 3 primary drugs. These findings suggest that drug
      resistant mycobacterial infections are becoming an important problem in the
      region.

PMID- 8863362
TI  - Detection of Pneumocystis carinii DNA by filtration of air.
AB  - The high incidence of pneumonia caused by Pneumocystis carinii in
      immunosuppressed patients makes it the most important parasite in non-tropical
      geographical regions. It has recently been shown to be a fungus, but several
      aspects of this organism are still poorly understood. A major question of
      clinical relevance is the nature of transmission and, thereby, the related
      problem of prevention. The mode of P. carinii transmission is thought to be air,
      but this is based on circumstantial evidence, the transmissive stage has not been
      identified. We attempted to capture P. carinii by filtration of air in the
      vicinity of cages containing P. carinii infected Wistar rats. Using nested
      polymerase chain reaction amplification of the thymidylate synthase gene to
      demonstrate P. carinii we were able to demonstrate P. carinii DNA on such
      filters. This strongly supports the suggested mechanism of transmission of
      Pneumocystis by means of airborne spores and suggests an approach to their
      isolation and characterization.

PMID- 8863363
TI  - Bacteriology of antrum in children with chronic maxillary sinusitis.
AB  - Swabs from 93 chronically inflamed maxillary sinuses in children were taken from
      aerobic and anaerobic bacteria during endoscopy. Bacterial growth was present in
      87/93 specimens (93%). Anaerobic bacteria were isolated in 81/87 culture-positive
      specimens (93%) and were recovered alone in 61 cases (70%) and mixed with aerobic
      or faculative bacteria in 20 (23%). Aerobic or facultative bacteria were present
      alone in six cases (7%). A total of 261 isolates (3/specimen), 19 (2.4/specimen)
      anaerobes and 69 (2.6/specimen) aerobes or facultatives, were isolated. The
      predominant anaerobic organisms were Bacteroides sp. and anaerobic cocci; the
      predominant aerobes or facultatives were Streptococcus sp. and Staphylococcus
      aureus. These findings indicate the important role of anaerobic organisms in
      chronic sinusitis.

PMID- 8863364
TI  - Continuous-monitoring blood culture screening system improves the detection of
      bacteremia in neutropenic patients.
AB  - One reason for the underdiagnosis of bacteremia as an etiology of fever in
      neutropenic patients might lie in inefficient blood culture techniques. This
      possibility was investigated in a retrospective study by comparing the efficacies
      of a manual and an automated blood culture system used to detect bacteremia in
      such patients. All neutropenic fever episodes accompanying all 93 intensive
      chemotherapy cycles of 26 consecutive patients with acute myelogenous leukemia
      (AML) enrolled in Finnish Leukemia Group AML 86 trial and treated in Oulu
      University Hospital over 3 1/2 years were analyzed. The chemotherapy protocol and
      the supportive care of the patients remained the same during the whole period. In
      1990-91 the blood cultures were made manually and in 1992-93 with an automated
      continuous-monitoring culture screening system. Evaluable febrile episodes
      numbered 53 during 1990-91 and 73 during 1992-93. There was a statistically
      significant increase (p < 0.05) of culture-positive episodes, from 21% to 40%,
      when the continuous-monitoring system was adopted. The new method proved to be
      better than the manual one in detecting bacteremia of neutropenic patients.

PMID- 8863365
TI  - A hospital outbreak of high-level beta-lactam-resistant Enterobacter spp.:
      association more with ampicillin and cephalosporin therapy than with nosocomial
      transmission.
AB  - We studied an 8 month outbreak of a 7-fold increased isolation rate of high-level
      beta-lactam-resistant Enterobacter spp. from clinical infections (20 patients, 22
      isolates: 20 E. cloacae, 2 E. aerogenes). In a case-control analysis the
      occurrence of resistant Enterobacter spp. was found to be associated with
      treatment with multiple antibiotics (p = 0.03), broad-spectrum beta-lactam agents
      (p = 0.0001) including ampicillin (p = 0.04), and cephalosporins (cefuroxime and
      cefotaxime, p = 0.004). Biochemical fingerprinting and pulsed-field gel
      electrophoresis (PFGE) typing showed no identity between the resistant isolates,
      indicating that neither cross-infection nor nosocomial transmission from a common
      source was the immediate cause of the problem. The outbreak was not paralleled by
      the overall Enterobacter spp. isolation rate or the antibiotic usage pattern in
      the hospital. Thus, the underlying cause of the outbreak remained obscure.

PMID- 8863366
TI  - Trimethoprim-sulfamethoxazole plus amikacin versus ceftazidime monotherapy as
      empirical treatment in patients with neutropenia and fever.
AB  - In a prospective randomized comparison, 217 episodes of fever (oral temperature >
      38.5 degrees C on 1, or 38.0 degrees C on 2 occasions with a minimum interval of
      4 h between recordings) during neutropenia (neutrophil count < 0.5 x 10(9)/I),
      patients were empirically treated with trimethoprim-sulfamethoxazole plus
      amikacin (TMP/SMZ plus AMI) or ceftazidime. Successful antibiotic treatment was
      defined as eradication of all signs, symptoms and microbiological evidence of
      infection on the primary therapy alone. The overall success rate did not differ
      between the 2 treatment groups: 31/102 (30%; 21-39%, 95% confidence interval, CI)
      for TMP/SMZ plus AMI and 41/115 (36%; 27-44%) for ceftazidime (difference 0.06 +/
      0.13, 95% CI). The corresponding numbers for documented infections were 12/50
      (24%; 12-36%) and 14/60 (23%; 12-35%), respectively (difference 0.01 +/- 0.16).
      One patient in the TMP/SMZ plus AMI group and 2 patients in the ceftazidime group
      died from Gram-negative bacteraemias within 72 h. No other early deaths were
      observed. Antibiotics were changed due to adverse events in 2 episodes of each
      treatment group. In conclusion, this study demonstrates that TMP/SMZ plus AMI
      combination is comparable (i.e. a difference of < 20%) to ceftazidime monotherapy
      with regard to efficacy and safety in haematological patients with severe
      neutropenia. Both regimens require frequent modifications, particularly in
      bacteraemic fever episodes. However, in centres with a low frequency of isolation
      of Pseudomonas and especially of multi-resistent Pseudomonas strains, TMP/SMZ
      plus AMI offers an inexpensive alternative for the empirical treatment of febrile
      neutropenia.

PMID- 8863367
TI  - No findings of enteroviruses in Swedish patients with chronic fatigue syndrome.
AB  - Enteroviruses have been proposed to cause an immune complex disease in the
      chronic fatigue syndrome. Altogether 34 patients with the chronic fatigue
      syndrome, according to criteria of the Centers for Disease Control, USA, were
      studied evenly over the seasons for the possible presence of a chronic
      enterovirus infection. In 11 patients, 1-5 faecal samples were collected at about
      6 month intervals for virus isolation before and after acid treatment, followed
      by ultracetrifugation at pH 3 to dissolve possible enterovirus-antibody
      complexes. Another 14 fecal samples were subjected to routine virus isolation
      alone. Seven pairs of serum-cerebrospinal fluid samples were analysed for cross
      reactive IgG antibody activity to enteroviruses. In 29 patients a muscle biopsy
      was collected for enterovirus polymerase chain reaction (PCR). We were unable to
      identify enteroviruses in any of these samples by any of these techniques. Our
      study does not confirm evidence for persistent enterovirus infection in the
      chronic fatigue syndrome.

PMID- 8863368
TI  - Recurrent vertebral osteomyelitis and psoas abscess caused by Streptococcus
      constellatus and Fusobacterium nucleatum in a patient with atrial septal defect
      and an occult dental infection.
AB  - We describe a case in which recurrent vertebral osteomyelitis and psoas abscess
      due to Streptococcus constellatus and Fusobacterium nucleatum developed in a
      patient with a previously unrecognized atrial septal defect with bidirectional
      shunts. Disease recurrence was ascribed to the presence of dental disease, which
      served as the source of infection. To the best of our knowledge, this is the
      first case in which vertebral osteomyelitis and psoas abscess have been
      associated with atrial septal defect.

PMID- 8863369
TI  - Invasive Candida norvegensis infection in immunocompromised patients.
AB  - Invasive infection with Candida norvegensis has previously been reported only
      once. Three new cases of invasive infection with C. norvegensis are described.
      One patient with acute myeloid leukaemia and neutropenic septicaemia had positive
      blood cultures with C. norvegensis, and 2 patients with AIDS and prolonged
      unexplained febrile cachexia had positive cultures of C. norvegensis from
      multiple sites, including pericardium, liver, kidneys lymph nodes and bone
      marrow, on autopsy. In severely immunocompromised patients, C. norvegensis
      appears to be an emerging new pathogen.

PMID- 8863370
TI  - Fatal outcome of disseminated candidosis after allogeneic bone marrow
      transplantation under treatment with liposomal and conventional amphotericin-B. A
      report of 4 cases with determination of the Mic values.
AB  - Four patients undergoing allogeneic bone marrow transplantation were treated with
      liposomal (3 patients) and conventional (one patient) amphotericin-B for
      disseminated candidosis. Candida krusei was isolated from 3, and C. glabrata from
      1 patient. The patients were treated with liposomal amphotericin-B in doses from
      3 to 5 mg/kg. The fourth patient received conventional amphotericin-B in a
      reduced dose due to renal impairment. The patients died from multiorgan failure
      due to disseminated fungal infection. In 1 case, the switch to the conventional
      drug resulted in clearance before death. The 3 fungus isolates, together with the
      fourth strain obtained from patient no. 4 without any exposition to liposomal
      amphotericin-B were tested for their susceptibility to conventional, liposomal
      and discoidal amphotericin-B. All strains showed good sensitivity to the
      conventional and discoidal drug. The minimal inhibitory concentrations (MIC) of
      liposomal amphotericin-B were 1 to 3 titre steps higher indicating a reduced
      sensitivity of the tested strains to this preparation. We conclude that the use
      of liposomal amphotericin-B is recommended mainly on the base of the low
      incidence of side-effects. Intensive microbial resistance tests, pharmacokinetic
      investigations and randomized studies are necessary before the conventional drug
      is replaced as the gold standard for systemic antimycotic therapy.

PMID- 8863371
TI  - Nosocomial cerebral aspergillosis: a report of 3 cases.
AB  - Cerebral aspergillosis carries a mortality rate close to 100%, especially in
      immunocompromised patients. We describe 3 patients who contracted cerebral
      aspergillosis after neurosurgery, 2 of whom survived after exhaustive surgical
      treatment and medical treatment with high doses of amphotericin B (once
      liposomal), 5-fluorocytosine and itraconazole. We review the few non-fatal cases
      of cerebral aspergillosis reported. We consider that surgical excision must be
      complete and repeated if necessary, always in combination with medical treatment.

PMID- 8863372
TI  - Chronic Prototheca meningitis.
AB  - A case of chronic meningitis caused by the achloric alga Prototheca wickerhamii
      is described, which has persisted for more than 6 years despite treatment with
      various antifungal agents. For the last year no treatment has been given, but the
      patient has no complaints.

PMID- 8863373
TI  - Recurrent bilateral anterior uveitis with hypopyon and rifabutin therapy.
AB  - Rifabutin is used in patients with human immunodeficiency virus infection to
      prevent and treat Mycobacterium avium complex infection. We report a case of
      recurrent bilateral anterior uveitis with hypopyon in a patient who was taking
      600 mg of rifabutin daily. The rate of recurrence with the continuation of
      rifabutin seems to be high, especially in the opposite eye (alternate uveitis
      with hypopyon); rifabutin should be discontinued if uveitis recurs.

PMID- 8863374
TI  - 11B[27Al] and 27Al[11B] double resonance experiments on a glassy sodium
      aluminoborate.
AB  - Cross-polarization/magic-angle spinning (CP/MAS) and rotational echo double
      resonance (REDOR) experiments involving two half-integer quadrupolar nuclei, 11B
      and 27Al, are reported, to demonstrate boron-aluminum connectivities in a model
      aluminoborate glass. A detailed study of the spin-lock behavior of 11B and 27Al
      proves to be a prerequisite for successful CP/MAS experiments. Under MAS
      conditions, two distinct boron sites are observed, corresponding to tetrahedral
      BO4/2- sites (nuclear electric quadrupole coupling constant near 0.3 MHz) and
      trigonal BO3/2 sites (nuclear electric quadrupole coupling constant near 2.7
      MHz). The BO4/2- sites are most successfully spin-locked in the adiabatic regime
      at high radio frequency (RF) field strengths, whereas for the BO3/2 sites optimum
      spin-lock conditions are achieved in the sudden regime (low RF field strengths).
      These differences can be exploited for spectral editing purposes in REDOR
      experiments. Using corresponding T1p filters, it becomes possible to measure
      individual REDOR dephasing curves for both types of boron sites. The results
      illustrate the possible utility of heteronuclear X-Y double resonance techniques
      in unravelling the intermediate range order in amorphous systems containing
      quadrupolar nuclei.

PMID- 8863375
TI  - The influence of molecular motion on cross-polarization in cross-linked
      elastomers.
AB  - The effect of molecular motion on the heteronuclear cross-polarization rate for
      the case of the spin-lock procedure was investigated. In applying heteronuclear
      solid state NMR techniques to mobile elastomer systems the influence of molecular
      motion cannot be neglected. Starting in the slow motion regime a strong collision
      model was used for predicting changes of the cross-polarization rate in the
      dipolar spectral density function of abundant spins. The dipolar correlation time
      and hence the cross-polarization rate is found to scale with the inverse of the
      correlation time of the molecular motion. The same behavior is obtained using a
      second approach valid in the intermediate molecular motion regime. This is based
      on the effect of the motion on the homonuclear and heteronuclear van-Vleck
      moments and leads to a linear dependence of the cross-polarization rate on the
      correlation time of molecular motion. This dependence was verified experimentally
      by 1H-13C high-resolution cross-polarization measurements on sulfur cross-linked
      elastomer systems. 13C rotating frame spin-lattice relaxation rate measurements
      were used to corroborate these data and the approximations used to evaluate the
      influence of molecular motion on cross-polarization rates. The dependence of
      these rates on the cross-link density of the elastomer network is analyzed and it
      is shown that they scale with the cross-link density. The correlation of the 1H
      13C cross-polarization rates with the dynamic storage moduli was demonstrated.

PMID- 8863376
TI  - Determination of 113Cd shielding tensor components in cadmium-phosphine complexes
      from 31P-decoupled 113Cd cross-polarisation/magic angle spinning spectra.
AB  - Owing to the simultaneous presence of various anisotropic interactions within the
      isolated M-31P and M(31P)2 fragments in solid transition metal phosphine
      complexes MX2.PR3 and MX2.2PR3 with, for instance, M = Cd, Hg or Pt, it is not
      normally possible to unequivocally determine the shielding tensor components of
      the metal nucleus M from simple 113Cd, 199Hg or 195Pt cross-polarisation/magic
      angle spinning (CP/MAS) spectra. In this paper it is shown that additional 31P on
      resonance high-power decoupling during the acquisition time does allow the
      determination of the shielding tensor components of M from CP/MAS spectra. Two
      cadmium(II) complexes, Cd(OAc)2.Pchex3, (chex = cyclohexyl) and Cd(ClO4)2.2Pchex3
      were chosen as examples; the 113Cd CP/MAS experiments were carried out at a low
      external magnetic field strength B0 = 2.35 T.

PMID- 8863378
TI  - Determination of 207Pb2+ chemical shift tensors from precise powder lineshape
      analysis.
AB  - 207Pb solid state NMR powder spectra at 296 K are presented for PbSO4, PbMoO4,
      PbCrO4, PbCO3, PbTiO3, PbZrO3, Pb(NO3)2, Pb(SCN)2, and PbS. Analysis for
      principal values of the anisotropic chemical shift tensors of the generally very
      broad spectra included the frequency dependent excitation of the pulse sequence
      used. Commonly used solid and liquid secondary shift standards for lead were
      studied with high precision as a function of temperature between 295 K and 315 K
      to establish a clean 207Pb shift scale. Errors in the existing literature are
      discussed.

PMID- 8863377
TI  - Determination of the 13C magnetic shielding tensor in partially oriented polymer
      systems.
AB  - It is shown that, for an oriented sample, the 13C magnetic shielding tensor of a
      specific nucleus can be determined from the spinning sideband intensities in a 2D
      spectrum obtained from a 13C rotor-synchronized 2D CPMAS experiment, originally
      designed by Harbison and co-workers (G.S. Harbison, V. Vogt and H.W. Spiess, J.
      Chem. Phys., 86(3) (1987) 1206; G.S. Harbison, H.W. Spiess, Chem. Phys. Lett.,
      124 (1986) 128). In our fitting procedure, we combined their multilinear
      regression analysis for the determination of the order parameters with a
      variation both of the principal values of the magnetic shielding tensor and of
      the direction of the principal axes relative to the molecule. The magnetic
      shielding principal elements of the nonprotonated aromatic carbon in
      poly(ethylene terephthalate) (PET) fibres and of the aromatic carbons in the
      central ring of an oriented liquid crystalline polymer network are reported. We
      estimate that the accuracy of the principal values is within 5 ppm.

PMID- 8863379
TI  - 1H MAS NMR spectroscopy of chemically modified silica gels: a fast method to
      characterize stationary interphases for chromatography.
AB  - Chemically modified silica gels used as stationary phases in chromatography have
      been investigated by means of solid-state 1H magic angle spinning (MAS) NMR
      spectroscopy. Since the organosilanes are bonded to the surface of the silica
      gel, their protons are diluted and possess a higher mobility in comparison to
      protons in pure organic solids. Thereby the usually strong homonuclear dipole
      dipole interactions among the protons are reduced and it is possible to obtain
      well-resolved 1H NMR spectra of the organic interphases with MAS-only techniques.
      Effects of temperature and magnetic field strength on the resolution of the
      spectra are examined as well as the dependence of T1 and T1pH relaxation times on
      temperature and spinning speed.

PMID- 8863380
TI  - Electronic structure of bridging halogen atoms in metal halide dimers studied by
      the AM1 method and NQR spectroscopy.
AB  - A nuclear quadrupole resonance (NQR) study of the electronic structure of
      bridging halogen atoms in dimers of transition and non-transition metal halides
      has been performed. An explanation of the differences in the NQR frequencies for
      transition and non-transition metal halides is proposed. The population of the
      bridging halogen atom orbitals and the metal-halogen bond lengths have been
      estimated by the AM1 method. The aim of this paper was to obtain a relationship
      describing the lengths of the metal-halogen bonds.

PMID- 8863381
TI  - Japan's health care system in the 21st century.

PMID- 8863382
TI  - Trends leading to the restructuring of health care systems: is the United States
      a leader or an outlier?

PMID- 8863383
TI  - A plan for a new health leader training course at Tokai University.

PMID- 8863384
TI  - Demand and needs on new health initiative leaders developments.

PMID- 8863385
TI  - Proposal for a host education center under WHO for the international development
      of new health initiative leaders.

PMID- 8863386
TI  - Clinical hematology. In-clinic analysis, quality control, reference values, and
      system selection.
AB  - An increasing number of veterinary practices are performing in-office hematology
      testing. Historically, this involved time-consuming, labor-intensive manual
      methods. A number of automated and semiautomated hematology instruments are now
      available for analysis of veterinary samples, which, when used properly, offer
      more efficient, precise testing than can be achieved through manual methods. This
      article reviews manual methods for performing a complete blood count and
      describes some of the available automated hematology instruments. Factors that
      affect test results and the importance of a quality assurance program are also
      discussed.

PMID- 8863387
TI  - Congenital erythrocyte enzyme deficiencies.
AB  - Congenital hemolytic anemias resulting from PK, PFK, and G6PD enzyme deficiencies
      have been reported in domestic animals. Dogs with PFK deficiency may have
      episodes of intravascular hemolysis with hemoglobinuria in addition to a
      persistent compensated hemolytic anemia. Patients with mild G6PD deficiency are
      not anemic but may show increased susceptibility to oxidant-induced erythrocyte
      injury. Persistent methemoglobinemia has been reported in dogs and cats with
      methemoglobin reductase enzyme deficiency. Affected animals have cyanotic
      appearing mucous membranes but show no or only mild clinical signs attributable
      to hypoxemia. Enzyme assays are usually done after acquired causes of hemolytic
      anemia and methemoglobinemia have been ruled out.

PMID- 8863388
TI  - The neutrophil. Function, disorders, and testing.
AB  - Normal neutrophil function requires the cooperation and coordination of many
      cellular activities within the neutrophil and cells of the vascular system. The
      free flowing neutrophil begins the process by "rolling" along the vessel wall.
      This first step in migration is mediated by selectins on the surface of
      neutrophils, platelets, and endothelial cells. Subsequent firm adhesion requires
      the collaboration of neutrophil integrins and membrane-expressed cellular
      adhesion molecules. The activated neutrophil also changes shape from a sphere to
      an elongated motile cell by the assembly of actin filaments. At the inflammatory
      focus the neutrophil may encounter material to be ingested and killed. The
      ingestion process is mediated by the same receptors that stimulate firm adherence
      to the vessel wall. The ingestion process stimulates the formation of active
      NADPH oxidase, which is critical for the formation of superoxide and subsequent
      components of the killing mechanism. The process of normal neutrophil function is
      complex and multifaceted, but luckily, defects in this system are extremely rare.
      Patients with persistent and recurrent infections should be carefully evaluated
      for underlying disease before primary neutrophil dysfunction is pursued.

PMID- 8863389
TI  - Myelopoiesis and myeloproliferative disorders.
AB  - Myeloid cells arise from a common stem cell whose development is regulated by
      stimulatory and inhibitory growth factors. Pluripotential hematopoietic stem
      cells are most influenced by IL-3, GM-CSF, and stem cell factor while committed
      progenitor cells are regulated by variable concentrations of GM-CSF, G-CSF, M
      CSF, IL-5, Epo, and Tpo. As a result of their common origin, a key point to
      remember about myeloproliferative disorders is the involvement of multiple cell
      lines in dysplastic and neoplastic conditions. Dysplastic changes may signal
      early neoplastic changes with cases progressing to acute leukemia.
      Myelodysplastic syndrome (MDS) is associated with anemia or multiple cytopenias,
      normal to hypercellular bone marrow, ineffective hematopoiesis, and less than 30%
      blast cells of all nucleated cells in the bone marrow. Chronic myeloid leukemias
      also have less than 30% blast cells of all nucleated cells in the bone marrow and
      are distinguished from MDS by elevated cell counts of one or more cell lines with
      mature forms predominating. Acute myeloid leukemias, often the end result of all
      myeloproliferative disorders, are recognized by equal or greater 30% blast cells
      of all nucleated cells in the bone marrow. Additional diagnostic information from
      cytochemical stains, immunohistochemical staining, and cytogenetic analysis can
      influence the final diagnosis when morphology alone is equivocal. In conclusion,
      prognosis and response to treatment are best determined by application of a
      uniform set of standards in evaluating hematolymphatic neoplasia. Critical to
      diagnosis are complete blood and bone marrow evaluations including observation
      for dysplastic changes and blast cell quantitation. In addition, evidence for
      tissue infiltration identified through cytologic or histologic evaluations of
      lymph node, spleen, or liver is recommended.

PMID- 8863390
TI  - Blood cell markers.
AB  - Cytochemistry and immunocytochemistry are important adjunctive technologies to
      the morphologic characterization of blood cells and hematopoietic neoplasms.
      Although cytochemistry is briefly discussed, the emphasis of this article is on
      the clinical application of flow cytometry and leukocyte monoclonal antibodies in
      veterinary medicine. Classification and significance of immunophenotyping in
      canine and feline lymphomas and immunodeficiencies such as feline
      immunodeficiency virus and feline leukemia virus are discussed.

PMID- 8863391
TI  - Platelets and coagulation. An update.
AB  - Accepted mechanisms of coagulation are being challenged as new proteins and
      feedback mechanisms are discovered and evaluated. These new proteins, including
      tissue factor pathway inhibitor, not only change the way we look at the
      coagulation mechanism, but also give us potential alternatives in treatment of
      hemophilia. Gene therapy continues to be a challenging research area, with
      hemophilia serving as the prototypic hereditary disease target. As acquired
      disorders of coagulation secondary to immune-mediated events are studied and
      better understood, our approaches to management of these cases will also change
      to the benefit of our patients.

PMID- 8863392
TI  - von Willebrand's disease in the dog and cat.
AB  - Von Willebrand's disease (vWD) is a bleeding disorder that is recognized commonly
      in dogs but rarely in cats. This article presents the pathophysiology and
      clinical features of vWD, including a discussion of inherited and acquired types
      of vWD. Laboratory evaluation and treatment of vWD are reviewed.

PMID- 8863394
TI  - An update on chemistry analyzers.
AB  - This update of six chemistry analyzers available to the clinician discusses
      several points that should be considered prior to the purchase of equipment.
      General topics include how to best match an instrument to clinic needs and the
      indirect costs associated with instrument operation. Quality assurance
      recommendations are discussed and common terms are defined. Specific instrument
      features, principles of operation, performance, and costs are presented. The
      information provided offers potential purchasers an objective approach to the
      evaluation of a chemistry analyzer for the veterinary clinic.

PMID- 8863393
TI  - Antithrombotic and fibrinolytic factors. A review.
AB  - Excessive or nonphysiologic thrombogenesis and fibrinolysis accompanies many
      diseases. Several specific proteins involved in the physiologic regulation and
      maintenance of blood in a fluid state are reviewed in this article. Assays for
      these proteins or evidence of their function (antithrombin III, protein C,
      protein S, plasminogen/plasmin, tissue plasminogen activator, plasminogen
      activator inhibitor I, fibrinogen/fibrin degradation products, and
      thrombin/antithrombin complexes) are described. Principles, general methodology,
      and application in veterinary medicine are discussed. Although most of the
      investigative work and knowledge concerning these proteins and assays has been in
      human beings, their use and application in veterinary medicine is becoming more
      available in research laboratories at referral centers and some larger commercial
      veterinary laboratories. Use and interpretation of these assays will help
      clinicians and researchers better understand pathophysiologic processes occurring
      in various diseases associated with thrombogenesis and excessive fibrinolysis.

PMID- 8863395
TI  - Pathophysiology of calcium, phosphorus, and magnesium metabolism in animals.
AB  - The goal of this article is to summarize key features of calcium, phosphorus, and
      magnesium pathophysiology and highlight some of the recent scientific
      accomplishments in these fields. The area of calcium physiology has been
      especially active due to the discovery of a new calcium-regulating hormone,
      parathyroid hormone-related protein, cloning of the parathyroid hormone receptor
      and identification of a cell membrane receptor for ionized calcium. Advances have
      also been made in understanding the role of phosphorus and the active form of
      vitamin D, 1,25-dihydroxyvitamin D in the pathogenesis of secondary
      hyperparathyroidism in patients with chronic renal failure. The role of magnesium
      in many pathologic processes, including cardiac disease, is gaining a heightened
      appreciation due to its function in many metabolic processes and the development
      of techniques to measure ionized magnesium concentrations.

PMID- 8863396
TI  - Strong ion difference approach to acid-base imbalances with clinical applications
      to dogs and cats.
AB  - Stewart's strong ion difference, first introduced more than 10 years ago, offers
      an innovative approach for the analysis of non-respiratory acid-base disorders.
      This article addresses the concept of strong ion difference and discusses its
      clinical applications. A brief review of base excess and anion gap is also
      included. Clinical cases are provided to demonstrate a step-by-step method using
      strong ion difference to evaluate nonrespiratory acid-base imbalances.

PMID- 8863397
TI  - Invasive cytology of internal organs. Cytology of the thorax and abdomen.
AB  - Invasive cytology of the thoracic and abdominal cavities can provide diagnostic
      information in a timely manner for the practitioner. The information depends on
      obtaining a quality sample followed by thorough cytologic evaluation. Diagnostic
      imaging can enhance the sampling process and minimize the risk. As an adjunct to
      the historic and clinical information, cytology is valuable in establishing a
      diagnosis or list of differentials and directing future diagnostics or therapy.
      The application of cytology of internal organs opens a new window for the
      differential diagnosis of disease.

PMID- 8863399
TI  - BSE research results suggest 'enhanced risk' of maternal transmission.

PMID- 8863398
TI  - Molecular tools for the diagnosis of animal diseases.
AB  - Molecular diagnostics is now commonplace in veterinary research laboratories. The
      advent of nonradioactive labeling systems has allowed the rapid spread of these
      techniques into commercial laboratories as well. The use of PCR, nucleic acid
      probes, and hybridization studies will undoubtedly shape the future of laboratory
      diagnostics for many infectious, neoplastic, and congenital diseases. Practicing
      veterinarians must become aware of the basic concepts behind these diagnostic
      tools. Molecular-based diagnostic tests are soon likely to be commercially
      available for use in clinical laboratories.

PMID- 8863400
TI  - Epidemiology of lameness in dairy cattle: the influence of cubicles and indoor
      and outdoor walking surfaces.
AB  - A survey of cubicles and indoor and outdoor walking surfaces on 37 farms served
      by four veterinary practices in Somerset, Cheshire, Wirral and west. Wales was
      carried out in 1989 to 1991. A study of the space requirements of
      Friesian/Holstein cows at pasture showed that they required approximately 240 cm
      x 120 cm lying space and a further 60 cm lunging space for rising. By these
      standards, 87 per cent of the cubicles were too short and 50 per cent were too
      wide or too narrow. Over 1500 observations on cows lying down, rising and
      standing indicated that only 12 per cent of the cubicles permitted real freedom
      of movement; 91 per cent of top partition rails were judged to be too low and 70
      per cent of bottom rails too low or too high. In addition, the kerb was very high
      in 76 per cent of the cubicles. As a result, 10 per cent of cows appeared
      moderately or severely restricted when lying down, 33 per cent when rising and 55
      per cent when standing. Over 2000 cubicle beds were also studied; 75 per cent had
      a concrete base and of those, 63 per cent were judged to have too little bedding
      and 11 per cent next to none. Higher incidences and prevalences of lameness were
      associated with limited borrowing space (P < 0.01) low bottom rails (P < 0.05),
      high kerbs (P < 0.05) and inadequate bedding (P < 0.01). Of 3190 walking
      surfaces, only 25 per cent were classified as satisfactory in the first winter
      and 34 per cent in the second. In general, surfaces in silage bays were too rough
      and those in other sites were too smooth. The farms with the smoothest indoor
      walking surfaces had a significantly higher incidence of lameness (P < 0.01). Of
      3335 outdoor walking surfaces only 25 per cent were classified as satisfactory,
      and 70 per cent were too rough. The incidence of lameness was not significantly
      related to these findings.

PMID- 8863401
TI  - Force-plate analysis of gait before and after surgical excision of calcified
      lesions of the supraspinatus tendon in two dogs.
AB  - Two dogs with supraspinatus calcifying tendinopathy were lame in their forelimbs
      and were treated by the surgical excision of the calcified lesion. The lameness
      in both dogs improved after surgery without additional medical treatment, as
      evidenced by force-plate analysis of their gait.

PMID- 8863402
TI  - Efficacy of a commercial competitive exclusion product against a chicken
      pathogenic Escherichia coli and E coli O157:H7.
AB  - The prevention of caecal colonisation of chicks by a poultry pathogenic
      Escherichia coli O20:K-:H8 and the human pathogenic E coli O157:H7 was studied in
      vivo in four one-week laboratory trials. Chicks were treated with a competitive
      exclusion product on the day of hatch and challenged one day later. The poultry
      pathogenic serotype showed higher levels of caecal colonisation than the human
      pathogenic serotype, but the protection against both pathogens was highly
      significant.

PMID- 8863403
TI  - Health status of dairy herds converting from conventional to organic dairy
      farming.

PMID- 8863404
TI  - Efficacy of triclabendazole against Fasciola hepatica in the donkey (Equus
      asinus).

PMID- 8863405
TI  - Cholangiocarcinoma in a goat.

PMID- 8863406
TI  - BSE and rabies policies: science or sophistry?

PMID- 8863407
TI  - Novel Psychrobacter species from Antarctic ornithogenic soils.
AB  - Ornithogenic soil is derived from the deposition of the fecal matter of various
      species of birds and is a major source of nutrient input in the Antarctic marine
      ecosystem. A significant proportion of microbiota of ornithogenic soil collected
      from an Adelie penguin colony in eastern Antarctica (Vestfold Hills ice-free
      zone) consisted of gram-negative, coccoid bacteria identified on the basis of
      their phospholipid ester-linked fatty acid and lipid class profiles as
      Psychrobacter strains. Phenotypic, genotypic, and 16S ribosomal DNA phylogenetic
      analyses revealed that the Antarctic psychrobacters belonged to three distinct
      groups. Comparisons with Psychrobacter immobilis and Moraxella phenylpyruvica
      reference cultures isolated from fish, seawater, poultry, and human clinical
      specimens revealed the relationships of these groups within the genus
      Psychrobacter. Two of the groups represent the following two novel species:
      Psychrobacter urativorans sp. nov. (type strain, strain ACAM 534) and
      Psychrobacter frigidicola sp. nov. (type strain, strain ACAM 304). The third
      group of strains included members of the previously described species P.
      immobilis (Juni and Heym 1986). In addition, M. phenylpyruvica (Bovre and
      Henriksen 1967) is renamed Psychrobacter phenylpyruvicus comb. nov. (type strain,
      strain ACAM 535) on the basis of 16S ribosomal DNA phylogenetic data. In general,
      the genus Psychrobacter could be differentiated from the related genera Moraxella
      and Acinetobacter by the fact that the members of the genus Psychrobacter are
      psychrotolerant or psychrophilic and halotolerant, which reflects the ubiquitous
      distribution of the genus in both marine and terrestrial environments. On the
      basis of the results of this and previous studies, the genus Psychrobacter is the
      predominant genus in ornithogenic soils in Antarctica and is diverse.

PMID- 8863408
TI  - Bordetella trematum sp. nov., isolated from wounds and ear infections in humans,
      and reassessment of Alcaligenes denitrificans Ruger and Tan 1983.
AB  - Ten strains recognized on the basis of a computer-assisted numerical comparison
      of whole-cell protein patterns as members of a novel species belonging to the
      family Alcaligenaceae were examined by using an integrated phenotypic and
      genotypic approach. This species, for which we propose the name Bordetella
      trematum sp. nov., was more closely related to the type species of the genus
      Bordetella (Bordetella pertussis) than to the type species of the genus
      Alcaligenes (Alcaligenes faecalis) and had the general characteristics of members
      of this family (i.e., a DNA base ratio in the range from 57 to 70 mol%, a fatty
      acid profile characterized by high percentages of 16:0, 17:0 cyclo, and 14:0 3OH,
      nonsaccharolytic metabolism, and several classical biochemical characteristics,
      including aerobic and microaerobic growth, catalase activity, assimilation of
      citrate, an absence of anaerobic growth, and an absence of acetylmethylcarbinol
      and indole production, gelatin liquefaction, and esculin hydrolysis). A
      reevaluation of the criteria used to classify Alcaligenes denitrificans Ruger and
      Tan 1983 and Achromobacter xylosoxidans Yabuuchi and Ohyama 1971 as subspecies of
      Alcaligenes xylosoxidans and additional evidence provided in recent studies
      revealed that, consistent with present standards, it is appropriate to consider
      these two taxa distinct species of the genus Alcaligenes.

PMID- 8863409
TI  - Phylogenesis of relapsing fever Borrelia spp.
AB  - The phylogenetic relationships of 20 relapsing fever (RF) Borrelia spp. were
      estimated on the basis of the sequences of rrs genes. Complete sequences were
      aligned and compared with previously published sequences, and the similarity
      values were found to be 97.7 to 99.9%. Phylogenetic trees were constructed by
      using the three neighbor-joining, maximum-parsimony, and maximum-likelihood
      methods. The results of the comparative phylogenetic analysis divided the RF
      Borrelia spp. into three major clusters. One cluster included Borrelia
      crocidurae, Borrelia duttonii, Borrelia recurrentis, and Borrelia hispanica.
      Another cluster comprised tow main branches with Borrelia coriaceae, Borrelia
      lonestari, and Borrelia miyamotoi on one side and Borrelia parkeri, Borrelia
      turicatae, and Borrelia hermsii on the other side. Borrelia anserina constituted
      the third cluster. The phylogenetic position of Borrelia persica was more
      uncertain. These results suggested that the taxonomy of these spirochetes should
      be revised. To overcome the problems of culturing the spirochetes, RF Borrelia
      primers were defined. Following PCR amplification of the rrs gene, restriction
      length fragment polymorphism could be used to distinguish between RF Borrelia
      strains.

PMID- 8863410
TI  - Emendation of the genus Planococcus and transfer of Flavobacterium okeanokoites
      Zobell and Upham 1944 to the genus Planococcus as Planococcus okeanokoites comb.
      nov.
AB  - The taxonomic position of Flavobacterium okeanokoites IFO 12536T (T = type
      strain) was determined by 16S rRNA gene sequencing and chemotaxonomic methods.
      Phylogenetic evidence derived from a 16S rRNA sequence analysis indicated that F.
      okeanokoites, which forms rod-shaped cells, belongs to the genus Planococcus,
      which forms spherical cells. A phylogenetically close relationship was supported
      by chemotaxonomic characteristics, such as the presence of menaquinone 7 and
      menaquinone 8 as major isoprenoid quinones, the presence of phosphatidylglycerol,
      bisphosphatydylglycerol, and phosphatidylethanolamine as cellular polar lipids,
      and the G + C content of the DNA (46.3 mol%). These data suggest that whether a
      cell is a rod or a coccus is not a generic criterion. Accordingly, we propose
      that F. okeanokoites should be transferred to the genus Planococcus and that the
      description of the genus Planococcus should be emended.

PMID- 8863411
TI  - Anaerofilum pentosovorans gen. nov., sp. nov., and Anaerofilum agile sp. nov.,
      two new, strictly anaerobic, mesophilic, acidogenic bacteria from anaerobic
      bioreactors.
AB  - Strictly anaerobic, gram-positive, nonsporing, thin rod-shaped organisms whose
      cells were 0.2 to 0.6 by 3 to 6 microns were isolated from a Hoechst
      Biohochreaktor (strain FaeT [T = type strain]) and from the biofilm population of
      a fixed-film reactor treating sour whey (strain FT). Strain FT was vigorously
      motile during early logarithmic growth by means of peritrichously inserted
      flagella, while strain FaeT was seldom motile and usually possessed no flagella.
      During the stationary growth phase both strains formed spheroplasts. The
      temperature optimum was close to 37 degrees C (temperature range for growth, > or
      = 17 to < 45 degrees C) and the pH optimum was 7.0 to 7.4 (pH range, 6.5 to 8.0)
      for both strains. The two organisms grew chemoorganotrophically on a number of
      mono- and disaccharides, including glucose and xylose; yeast extract was required
      for growth. The principal fermentation products from glucose included lactate,
      acetate, ethanol, formate, and CO2. Hydrogen was not generated. The G + C
      contents of the DNAs of strains FaeT and FT were 55 and 54.5 mol%, respectively.
      The cell wall architecture was typical of gram-positive bacteria; the cells had
      an extraordinarily thin type A3 alpha' peptidoglycan layer containing muramic
      acid. Analysis of 16S ribosomal DNA sequences of the two new isolates
      demonstrated that they represent members of a new genus of bacteria in
      Clostridium cluster IV of the domain Bacteria and that the misclassified organism
      Fusobacterium prausnitzii and Clostridium leptum are among their closest
      relatives. The names Anaerofilum pentosovorans gen. nov., sp. nov. (type strain,
      strain Fae [= DSM 7168]) and Anaerofilum agile sp. nov. (type strain, strain F [=
      DSM 4272]) are proposed.

PMID- 8863412
TI  - Gordona hirsuta sp. nov.
AB  - Bacterial strain K718aT (T = type strain), which was isolated from the packing
      material of a biofilter used for deodorization of animal-rendering plant
      emissions, was subjected to a polyphasic taxonomic study in which physiological,
      chemotaxonomic, and genomic methods were used. On the basis of the chemotaxonomic
      and physiological properties found and the results of 16S ribosomal DNA sequence
      comparisons, it was evident that strain K718aT belongs to a new species in the
      genus Gordona. We propose that strain K718a should be the type strain of the new
      species Gordona hirsuta.

PMID- 8863413
TI  - Reduction of benzyl viologen distinguishes genera of the class Mollicutes.
AB  - We tested the ability of 62 growing strains belonging to the class Mollicutes to
      reduce the redox indicator and free-radical generator 1,1'-dibenzyl-4,4'
      bipyridinium dichloride (benzyl viologen [BV]) to a blue-violet-purple color. BV
      was reduced by 12 Acholeplasma species but not by Acholeplasma multiforme PN525T
      (T = type strain). BV was also reduced by five of nine Mesoplasma species and by
      four of six Entomoplasma species. BV was not reduced by 19 Mycoplasma species,
      six Spiroplasma species, five unnamed Spiroplasma strains belonging to different
      serogroups, three Ureaplasma species, and one unnamed Ureaplasma strain. The BV
      reducing ability was localized in the membrane of Acholeplasma laidlawii B-PG9
      and was dependent on NADH. Reduction of BV could be expressed in mixed cultures,
      and this activity may be useful for recognizing the contaminating presence of an
      Acholeplasma species. The reductive BV response may have phylogenetic value. We
      believe that the test described in this paper readily distinguishes all
      Acholeplasma species and some Mesoplasma and Entomoplasma species from all
      Mycoplasma, Spiroplasma, and Ureaplasma species tested.

PMID- 8863414
TI  - Comparative metabolism of Mesoplasma, Entomoplasma, Mycoplasma, and Acholeplasma.
AB  - Cytoplasmic fractions from species of the Mollicutes genera Entomoplasma,
      Mesoplasma, Mycoplasma, and Acholeplasma were assayed for NADH oxidase (NADH ox),
      ATP- and PPi-dependent phosphofructokinase (PFK), ATP- and PPi-dependent
      deoxyguanosine kinase (dGUOK), thymidine kinase (TK), TMP kinase (TMPK), glucose
      6-phosphate dehydrogenase (G6Pde), lactate dehydrogenase (LDH), malate
      dehydrogenase (MDH), phosphoenolpyruvate carboxylase, hypoxanthine-guanine
      phosphoribosyl transferase, dUTPase, and uracil-DNA glycosylase (UNG) activities.
      Membrane fractions were also examined for NADH ox activity. These activities were
      used as indicators of the presence and relative activities of major Mollicutes
      metabolic and DNA repair pathways. This was the first study to determine the
      presence of these enzymes in members of the genera Entomoplasma and Mesoplasma.
      Using the data obtained, we constructed a preliminary scheme for distinguishing
      genera of the class Mollicutes on the basis of the results of signature
      functional enzyme assays. This scheme includes phylogenetic relationships deduced
      from rRNA analyses, but is more informative with respect to metabolic potential.
      The criteria used include the presence of PPi-dependent PFK, urease, dUTPase, and
      dGUOK activities. Entomoplasma ellychniae ELCN-1T (T = type strain), Entomoplasma
      melaleucae M-1T, Mesoplasma seiffertii F7T, Mesoplasma entomophilum TACT,
      Mesoplasma florum L1T, Mycoplasma fermentans PG18T, and Acholeplasma multilocale
      PN525T were similar in most respects. NADH ox activity was localized in the
      cytoplasm of these organisms. These strains had ATP-dependent PFK, MDH, LDH, ATP-
      and PPi-dependent dGUOK, and UNG activities, but not dUTPase or G6Pde activities.
      In contrast, Acholeplasma equifetale C112T, Acholeplasma oculi 19LT, Acholeplasma
      hippikon C1T, Acholeplasma modicum PG49T, and Acholeplasma morum 72-043T had
      membrane-localized NADH ox activity, PPi-dependent PFK, G6Pde, and dUTPase
      activities, and significantly lower MDH and LDH activities and exhibited a faster
      rate with PPi than with ATP in the dGUOK reaction. All of the members of the
      Mollicutes tested had hypoxanthine-guanine phosphoribosyl transferase,
      phosphoenolpyruvate carboxylase, and (except for Mesoplasma entomophilum TAC(T))
      UNG activities. All of the Acholeplasma strains except Acholeplasma multilocale
      PN525T had TK, TMPK, and UNG activities. Mesoplasma entomophilum TAC(T) was
      distinguished by having no detectable dUTPase, UNG, TK, and TMPK activities,
      indicating that there is a severe restriction in or an absence of a synthetic
      route to dTTP. Our data also suggest that A. multilocale PN525T is a member of an
      unrecognized metabolic subgroup of the genus Acholeplasma or is not an
      Acholeplasma strain.

PMID- 8863415
TI  - Comparison of partial citrate synthase gene (gltA) sequences for phylogenetic
      analysis of Bartonella species.
AB  - Nucleotide base sequence data were obtained for a 940-bp fragment of the citrate
      synthase-encoding gene (gltA) of representatives of the eight validly described
      Bartonella species and seven uncharacterized Bartonella strains obtained from
      small mammals. Complete 16S rRNA gene sequences were also determined for the
      uncharacterized strains, and these sequences revealed that each strain had a
      unique sequence which was very similar to the sequences of the previously
      recognized Bartonella species. A comparison of the gltA sequences of the
      different Bartonella species revealed that the levels of similarity between
      sequences were 83.8 to 93.5%, whereas comparisons of sequences obtained from
      different strains of the same species revealed that the levels of similarity were
      more than 99.8%. One of the uncharacterized strains had a gltA sequence that
      matched the sequence of Bartonella elizabethae, three uncharacterized strains had
      sequences which were more than 99.6% similar to each other (but less than 93.5%
      similar to any other sequence), and the remaining three uncharacterized strains
      each exhibited less than 93.5% sequence similarity to other Bartonella species or
      isolates. Phylogenetic trees were inferred from multiple alignments of both gltA
      and 16S ribosomal DNA (rDNA) sequences. Whereas the proposed intra-Bartonella
      architecture of trees inferred from 16S rDNA sequence data by using both distance
      matrix and parsimony methods had virtually no statistical support, the trees
      inferred from the gltA sequence data contained four well-supported lineages in
      the genus. The gltA-derived phylogeny appears to be more useful than the
      phylogeny derived from 16S rDNA sequence data for investigating the evolutionary
      relationships of Bartonella species, and the validity of the lineages identified
      by the gltA analysis is discussed in this paper.

PMID- 8863416
TI  - Phylogenetic analysis of Borrelia species based on flagellin gene sequences and
      its application for molecular typing of Lyme disease borreliae.
AB  - We determined almost complete flagellin gene sequences of various Borrelia
      species and aligned them with previously published sequences. A neighbor-joining
      phylogenetic analysis showed that the genus Borrelia was divided into the
      following three major clusters: New World relapsing fever borreliae (Borrelia
      turicatae, Borrelia parkeri, and Borrelia hermsii), Old World relapsing fever
      borreliae (Borrelia crocidurae, Borrelia duttonii, and Borrelia hispanica), and
      Lyme disease borreliae (Borrelia burgdorferi sensu stricto, Borrelia garinii, and
      Borrelia afzelii). Agents of animal spirochetosis (Borrelia coriaceae and
      Borrelia anserina) and species of unknown pathogenicity (Borrelia miyamotoi and
      Borrelia lonestari) were related to relapsing fever borreliae. Although the Lyme
      disease borreliae, two related species (Borrelia japonica and Borrelia
      andersonii), and some newly described genomic groups (groups PotiB2, VS116,
      DN127, Hk501, and Ya501) were closely related to each other, each taxon formed an
      independent branch on the phylogenetic tree. The data obtained in this study
      indicate that the flagellin genes are useful in Borrelia taxonomy. To distinguish
      the Lyme disease borreliae from related organisms easily, we designed an
      oligonucleotide primer set for the flagellin gene and performed a PCR-restriction
      fragment length polymorphism (PCR-RFLP) analysis. The primer set amplified an
      approximately 580-bp DNA fragment that included species-specific restriction
      sites, and HapII, HhaI, CelII, HincII, or DdeI digestion of the product resulted
      in distinctively different PCR-RFLP patterns. The PCR-RFLP typing method which we
      developed should facilitate rapid identification of Lyme disease borreliae and
      related organisms obtained from biological and clinical specimens.

PMID- 8863417
TI  - Helicobacter trogontum sp. nov., isolated from the rat intestine.
AB  - A new Helicobacter species that colonizes the colonic mucosa of Wistar and
      Holtzman rats was isolated and characterized. This bacterium was gram negative,
      its cells were rod shaped with pointed ends, and its protoplasmic cylinder was
      entwined with periplasmic fibers. It was catalase and oxidase positive, rapidly
      hydrolyzed urea, and was susceptible to metronidazole and resistant to
      cephalothin and nalidixic acid. The new organism was microaerophilic and grew at
      42 degrees C, a feature that differentiates it from two other murine intestine
      colonizers, Helicobacter hepaticus and Helicobacter muridarum. On the basis of
      16S rRNA sequence analysis data, the new organism was identified as a
      Helicobacter species that is most closely related to H. hepaticus. This bacterium
      is named Helicobacter trogontum. The type strain is strain LRB 8581 (= ATCC
      700114).

PMID- 8863418
TI  - High degree of similarity between Chromatium vinosum and Chromatium minutissimum
      as revealed by riboprinting.
AB  - The riboprinting technique (restriction fragment length polymorphism [RFLP]
      analysis of PCR-amplified ribosomal DNA) was used to study five strains
      representing three species of the genus Chromatium. An RFLP analysis following
      digestion of the amplified small-subunit ribosomal DNA with 25 restriction
      enzymes revealed that the patterns obtained for all strains of Chromatium vinosum
      were identical. Chromatium gracile was different from C. vinosum with seven
      enzymes. On the other hand, Chromatium minutissimum produced the same patterns as
      C. vinosum with all enzymes, indicating that these organisms have a high degree
      of similarity. An RFLP analysis of the PCR-amplified spacer sequence between the
      16S and 23S ribosomal DNAs gave similar results except that there was a larger
      number of differences between C. gracile and the other organisms examined.

PMID- 8863419
TI  - A proposal to transfer Microbispora bispora (Lechevalier 1965) to a new genus,
      Thermobispora gen. nov., as Thermobispora bispora comb. nov.
AB  - We determined almost complete 16S rRNA gene sequences of two Microbispora bispora
      (Lechevalier 1965) strains, ATCC 19993T (T = type strain) and JCM 3082. The two
      sequences were 99% similar to each other but exhibited only 81 to 87.8%
      similarity with the 16S rRNA gene sequences of seven other Microbispora strains.
      A phylogenetic analysis revealed that the two sequences clustered not only
      distantly from other Microbispora strains, but also outside the cluster
      containing members of the family Streptosporangiaceae. On the basis of the
      results of our phylogenetic analysis and the results of a comprehensive review of
      the genus Microbispora by Miyadoh et al. (S. Miyadoh, S. Amano, H. Tohyama, and
      T. Shomura, J. Gen. Microbiol. 136:1905-1913, 1990) in which chemotaxonomic and
      DNA-DNA hybridization analyses were performed, we propose that Microbispora
      bispora should be transferred to a new genus, Thermobispora gen. nov., as
      Thermobispora bispora comb. nov.

PMID- 8863420
TI  - Proposal for two new genera, Brevibacillus gen. nov. and Aneurinibacillus gen.
      nov.
AB  - 16S rRNA gene sequences of the type strains of 11 species belonging to the
      Bacillus brevis and Bacillus aneurinolyticus groups were determined. On the basis
      of the results of gene sequence analyses, these species were separated into two
      clusters. The B. brevis cluster included 10 species, namely, Bacillus brevis,
      Bacillus agri, Bacillus centrosporus, Bacillus choshinensis, Bacillus parabrevis,
      Bacillus reuszeri, Bacillus formosus, Bacillus borstelensis, Bacillus
      laterosporus, and Bacillus thermoruber. Bacillus aneurinolyticus and Bacillus
      migulanus belonged to the B. aneurinolyticus cluster. Moreover, the two clusters
      were phylogenetically distinct from other Bacillus, Amphibacillus,
      Sporolactobacillus, Paenibacillus, and Alicyclobacillus species. On the basis of
      our data, we propose reclassification of the B. brevis cluster as Brevibacillus
      gen. nov. and reclassification of the B. aneurinolyticus cluster as
      Aneurinibacillus gen. nov. By using 16S rRNA gene sequence alignments, two
      specific PCR amplification primers were designed for differentiating the two new
      genera from each other and from other aerobic, endospore-forming organisms.

PMID- 8863421
TI  - Spiroplasma corruscae sp. nov., from a firefly beetle (Coleoptera: Lampyridae)
      and tabanid flies (Diptera: Tabanidae).
AB  - Spiroplasma strain EC-1T (T = type strain), which was isolated from the gut of a
      lampyrid beetle (Ellychnia corrusca) in Maryland, was serologically distinct from
      other spiroplasma species and groups. Similar strains were obtained from other E.
      corrusca specimens, and, later, numerous isolates of similar or partially related
      strains were obtained from several species of tabanid files. Cells of strain EC
      1T were helical, motile filaments that were bound by a single cytoplasmic
      membrane, and there was no evidence of a cell wall. The cells were filterable
      through 220-nm-pore-size membrane filters but not through 100-nm-pore-size
      membrane filters. The organism was absolutely resistant to penicillin (1,000
      U/ml) and required sterol for growth. Strain EC-1T grew well in M1D and SP-4
      liquid media and could be cultivated in the Edward formulation of conventional
      mycoplasma medium and in 1% serum fraction medium. Optimal growth occurred at 32
      degrees C (doubling time, 1.5 h). Strain EC-1T multiplied at 10 to 41 degrees C,
      but not at 5 or 43 degrees C. This organism produced acid from glucose, but did
      not hydrolyze arginine or utilize urea. The guanine-plus-cytosine content of the
      DNA was determined to be 26.3 mol% by the melting temperature method and 27.0
      mol% by the buoyant density method. As a result of our studies, strain EC-1 (=
      ATCC 43212) is designated the type strain of a new species, Spiroplasma
      corruscae.

PMID- 8863422
TI  - Actinobacillus minor sp. nov., Actinobacillus porcinus sp. nov., and
      Actinobacillus indolicus sp. nov., three new V factor-dependent species from the
      respiratory tract of pigs.
AB  - The results of DNA-DNA relatedness experiments and comparisons of sequences of
      genes coding for 16S rRNA were used to determine the genetic relationships of
      selected V factor-dependent species belonging to the family Pasteurellaceae and
      obtained from the porcine respiratory tract. These results showed that the Minor
      group and taxa C, D plus E, and F are distinct phylogenetic groups that are
      separate from each other and from other members of the family Pasteurellaceae. On
      the basis of these results, three new species, corresponding to the Minor group,
      taxa D plus E, and taxon F, are proposed; the names of these new species are
      Actinobacillus minor (type strain, NM305), Actinobacillus porcinus (type strain,
      NM319), and Actinobacillus indolicus (type strain, 46KC2), respectively.

PMID- 8863423
TI  - Phylogeny of oral asaccharolytic Eubacterium species determined by 16S ribosomal
      DNA sequence comparison and proposal of Eubacterium infirmum sp. nov. and
      Eubacterium tardum sp. nov.
AB  - 16S rRNA gene sequences of Eubacterium brachy, Eubacterium nodatum, Eubacterium
      saphenum, Eubacterium timidum, and two previously unnamed taxa were determined.
      The results of a phylogenetic analysis indicated that all of the strains
      sequenced belonged to a deep branch of the low-G+C-content gram-positive group.
      The levels of 16S ribosomal DNA sequence similarity between species were low,
      suggesting that a number of genera may be represented in this group. The
      representatives of the two unnamed taxa, which were isolated from patients with
      periodontitis, were clearly distinct from the previously described species, and,
      therefore, the following two new species are proposed: Eubacterium infirmum (type
      strain, NCTC 12940) and Eubacterium tardum (type strain, NCTC 12941).

PMID- 8863424
TI  - Phylogeny of Prosthecobacter, the fusiform caulobacters: members of a recently
      discovered division of the bacteria.
AB  - Prosthecobacter fusiformis is morphologically similar to caulobacters; however,
      it lacks a dimorphic life cycle. To determine the relatedness of the genus
      Prosthecobacter to dimorphic caulobacters and other prosthecate members of the
      alpha subgroup of the Proteobacteria (alpha-Proteobacteria), we isolated and
      sequenced 16S rRNA genes from four Prosthecobacter strains. Surprisingly, the
      results of phylogenetic analyses placed the fusiform caulobacters in a deeply
      rooted division of the Bacteria that was most closely affiliated with the
      Planctomyces-Chlamydia group and only distantly related to the alpha
      Proteobacteria. The genus Prosthecobacter shares a common lineage in this
      division with Verrucomicrobium spinosum, a polyprosthecate, heterotrophic
      bacterium. Consistent with this phylogenetic placement, menaquinones were
      isolated from Prosthecobacter strains and menaquinones have been isolated from
      Verrucomicrobium strains and planctomycetes but not from members of the alpha
      Proteobacteria. Thus, the genus Prosthecobacter is a second genus in the recently
      described order Verrucomicrobiales. Members of the genus Prosthecobacter are
      susceptible to beta-lactam antibiotics and contain mesodiaminopimelic acid,
      indicating that they, unlike members of the Planctomycetales or Chlamydiales,
      have peptidoglycan cell walls. This major phenotypic difference, together with
      the phylogenetic independence of the verrucomicrobia, indicates that these
      bacteria and the sources of related 16S ribosomal DNAs obtained from soils,
      freshwater, and the marine pelagic environment represent an unrecognized division
      of the Bacteria.

PMID- 8863425
TI  - Leucobacter komagatae gen. nov., sp. nov., a new aerobic gram-positive,
      nonsporulating rod with 2,4-diaminobutyric acid in the cell wall.
AB  - A new aerobic, gram-positive, nonsporulating rod-shaped organism is described:
      Strain IFO 15245T (T = type strain) has the following characteristics: the
      menaquinone contains a side chain with 11 isoprenyl units; the guanine-plus
      cytosine content of the DNA is 66.2 mol%; 2,4-diaminobutyric acid, glutamic acid,
      alanine, glycine, and gamma-aminobutyric acid are present in the cell wall at a
      molar ratio of ca. 1:1:2:1:1; and glucose and galactose are also present in the
      cell wall. A comparison of partial 16S rRNA sequences revealed that IFO 15245T
      represents a distinct line of descent within the gram-positive bacteria with high
      guanine-plus-cytosine contents. The taxonomic characteristics of this organism
      are different from those of previously described aerobic, gram-positive,
      nonsporulating, rod-shaped bacteria. The name Leucobacter komagatae gen. nov.,
      sp. nov., is proposed for this organism. The type strain is strain IFO 15245.

PMID- 8863426
TI  - Sinorhizobium medicae sp. nov., isolated from annual Medicago spp.
AB  - The taxonomic position of isolates of a new genomic species (designated genomic
      species 2) obtained from several annual Medicago species and originating from
      different geographical locations was established through the results of
      phenotypic tests (including the results of auxanographic and biochemical tests
      and symbiotic properties) and 16S rRNA phylogenetic inferences. A comparison of
      the complete 16S rRNA sequence of a representative of genomic species 2 (strain A
      321T [T = type strain]) with the 16S rRNA sequences of other members of the
      Rhizobiaceae and closely related taxa showed that genomic species 2 was
      phylogenetically related to Sinorhizobium meliloti, Sinorhizobium fredii,
      Sinorhizobium saheli, and Sinorhizobium teranga. The levels of sequence
      similarity and observed numbers of nucleotide substitutions in Sinorhizobium
      strains indicated that A 321T and S. meliloti exhibited the highest level of
      sequence similarity (99.7%), with four nucleotide substitutions and one deletion.
      The results of a numerical analysis based on data from 63 auxanographic and
      biochemical tests clearly separated genomic species 2 isolates from S. meliloti.
      Genomic species 2 isolates nodulated and fixed nitrogen with Medicago polymorpha,
      whereas S. meliloti isolates were ineffective and formed rudimentary nodules on
      this host plant. On the basis of phenotypic and 16S sequence analysis data,
      genomic species 2 isolates cannot be assigned to a previously described species.
      We propose that these isolates belong to a new species, Sinorhizobium medicae.

PMID- 8863427
TI  - Oxidation of thiosulfate by a new bacterium, Bosea thiooxidans (strain BI-42)
      gen. nov., sp. nov.: analysis of phylogeny based on chemotaxonomy and 16S
      ribosomal DNA sequencing.
AB  - A gram-negative bacterium which was capable of oxidizing reduced inorganic sulfur
      compounds was isolated from agricultural soil and designated BI-42. This new
      isolate grew on a wide range of organic substrates but was not able to grow
      autotrophically and lacked ribulose 1,5-bisphosphate carboxylase, a key enzyme of
      carbon dioxide fixation. These results suggested that strain BI-42 was a
      chemolithoheterotroph. Ammonia and nitrate were not used as sole nitrogen sources
      for growth, and strain BI-42 lacked glutamate synthase activity, which resulted
      in glutamate auxotrophy. The glutamate dehydrogenase activity of this organism
      was apparently insufficient for ammonia assimilation. On the basis of the results
      of additional biochemical tests, the G + C content of the DNA, the results of a
      respiratory ubiquinone analysis, the results of a 16S ribosomal DNA sequence
      analysis, the fatty acid composition, and the results of a membrane lipid
      analysis, strain BI-42 was identified as a phylogenetically and physiologically
      distinct taxon belonging to the alpha subclass of the Proteobacteria. Bosea
      thiooxidans gen. nov., sp. nov. is the name proposed for this taxon.

PMID- 8863428
TI  - A polyphasic reassessment of the genus Paenibacillus, reclassification of
      Bacillus lautus (Nakamura 1984) as Paenibacillus lautus comb. nov. and of
      Bacillus peoriae (Montefusco et al. 1993) as Paenibacillus peoriae comb. nov.,
      and emended descriptions of P. lautus and of P. peoriae.
AB  - Seventy-seven strains representing 10 species in the Paenibacillus polymyxa 16S
      rRNA group and 3 other species that exhibit phenetic relatedness to members of
      this group, Bacillus lautus, "Bacillus longisporus," and Bacillus peoriae, were
      characterized genotypically and phenotypically by performing an amplified
      ribosomal DNA restriction analysis, a randomly amplified polymorphic DNA
      analysis, a fatty acid methyl ester analysis, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of whole-cell proteins, pyrolysis mass
      spectrometry, and API and other routine phenotypic tests. These analyses revealed
      distinct clusters representing Paenibacillus alvei, Paenibacillus amylolyticus,
      Paenibacillus azotofixans, Paenibacillus durum, Paenibacillus larvae subsp.
      larvae, Paenibacillus larvae subsp. pulvifaciens, B. lautus, Paenibacillus
      macerans, Paenibacillus macquariensis, B. peoriae, P. polymyxa, and Paenibacillus
      validus, which confirmed the distinctness of these species, but appreciable
      within-species heterogeneity was observed in P. alvei, B. lautus, P. macerans, P.
      polymyxa, and P. validus. The type strain of Paenibacillus pabuli did not cluster
      with other strains of this species, and in several analyses a relationship
      between strains of P. pabuli and "B. longisporus" was observed. As the analyses
      showed that B. lautus and B. peoriae are closely related to the genus
      Paenibacillus, these species are reclassified as members of this genus.

PMID- 8863429
TI  - Analysis of the beta' subunit of DNA-dependent RNA polymerase does not support
      the hypothesis inferred from 16S rRNA analysis that Oenococcus oeni (formerly
      Leuconostoc oenos) is a tachytelic (fast-evolving) bacterium.
AB  - rRNA sequencing has shown that leuconostocs comprise three distinct phylogenetic
      lineages which have been designated separate genera (viz., the genera Leuconostoc
      sensu stricto, Oenococcus, and Weissella). In addition, the 16S rRNA line formed
      by Oenococcus oeni (formerly Leuconostoc oenos) is exceptionally long; this fact,
      together with variations in the compositions of conserved positions in the 16S
      rRNA, has led to the hypothesis (D. Yang and C. R. Woese, Syst. Appl. Microbiol.
      12:145-149, 1989) that this organism is a fast-evolving bacterium. Previous
      evidence that the leuconostocs should be divided into three genera and that O.
      oeni is an example of tachytelic evolution has come solely from rRNA analyses. In
      this study we seqenced the rpoC gene encoding the beta' subunit of DNA-dependent
      RNA polymerase of leuconostocs and performed a comparative phylogenetic analysis.
      The subdivision of the leuconostocs into three distinct lineages was confirmed by
      the rpoC gene data, but no evidence that indicated that O. oeni is evolving at an
      extraordinary rate was found. If O. oeni is truly tachytelic, then fast-evolving
      phenomena would be expected to occur throughout the whole genome, including this
      independent molecular chronometer.

PMID- 8863430
TI  - Isolation and characterization of Desulfitobacterium frappieri sp. nov., an
      anaerobic bacterium which reductively dechlorinates pentachlorophenol to 3
      chlorophenol.
AB  - An anaerobic bacterium, strain PCP-1T (T = type strain), which dechlorinates
      pentachlorophenol (PCP) to 3-chlorophenol, was isolated from a methanogenic
      consortium. This organism is a spore-forming rod-shaped bacterium that is
      nonmotile, asaccharolytic, and Gram stain negative but Gram type positive as
      determined by electron microscopic observations. Inorganic electron acceptors,
      such as sulfite, thiosulfate, and nitrate (but not sulfate), stimulate growth in
      the presence of pyruvate and yeast extract. The optimum pH and optimum
      temperature for growth are 7.5 and 38 degrees C, respectively. The dechlorination
      pathway is: PCP-->2,3,4,5-tetrachlorophenol -->3,4,5-trichlorophenol-->3,5
      dichlorophenol-->3-chlorophenol. This bacterium dechlorinates several different
      chlorophenols at ortho, meta, and para positions; exceptions to this are 2,3
      dichlorophenol, 2,5-dichlorophenol, 3,4-dichlorophenol, and the
      monochlorophenols. The time course of PCP dechlorination suggests that two enzyme
      systems are involved in dehalogenation in strain PCP-1T. One system is inducible
      for ortho dechlorination, and the second system is inducible for meta and para
      dechlorinations. A 16S rRNA analysis revealed that strain PCP-1T exhibits 95%
      homology with Desulfitobacterium dehalogenans JW/IU-DC1, an anaerobic bacterium
      which can dehalogenate chlorophenols only in ortho positions. These results
      suggest that strain PCP-1T is a member of a new species and belongs to the
      recently proposed genus Desulfitobacterium. Strain PCP-1T differs from D.
      dehalogenans JW/IU-DC1 by its broader range of chlorophenol dechlorination.
      Strain PCP-1 is the type strain of the new species, Desulfitobacterium frappieri.

PMID- 8863431
TI  - Classification of bacteria nodulating Lathyrus japonicus and Lathyrus pratensis
      in northern Quebec as strains of Rhizobium leguminosarum biovar viciae.
AB  - The diversity of two populations of rhizobia isolated from Lathyrus japonicus (30
      strains) and Lathyrus pratensis (49 strains) growing in northern regions of
      Quebec, Canada, was determined on the basis of phenotypic characteristics,
      multilocus enzyme electrophoresis, DNA-DNA homology, and 16S ribosomal DNA
      sequencing. According to numerical analysis of phenotypic characteristics,
      strains were divided into four groups. Strains isolated from L. pratensis fell in
      groups I to III; the latter included reference strains of Rhizobium
      leguminosarum. All strains isolated from L. japonicus were included in group IV.
      All strains had nodulation characteristics similar to those of R. leguminosarum
      bv. viciae. Strains isolated from L. japonicus originating from an arctic region
      were usually able to grow at 5 degrees C and were more likely to be tolerant to
      copper (CuCl2.H2O, 100 micrograms/ml) and lead [Pb(CH3COO)2, 500 micrograms/ml]
      than strains isolated from L. pratensis from a boreal zone. However, both
      populations of Lathyrus strains were adapted to the cold in comparison to
      reference strains from temperate regions. Each population had similar genetic
      diversity (H = 0.45), determined by multilocus enzyme electrophoresis of the loci
      encoding eight enzymes, but the diversity obtained by analyzing all strains
      including the reference strains (H = 0.58) was higher. Representative strains of
      both populations showed high levels of DNA homology among themselves and with R.
      leguminosarum. Partial sequences of the 16S ribosomal RNA genes were similar to
      those reported for R. leguminosarum bv. viciae. We conclude that the strains
      isolated from L. japonicus and L. pratensis belong to R. leguminosarum bv. viciae
      but are distinguishable by growth at 5 degrees C, which is a characteristic
      related to their geographic origin.

PMID- 8863432
TI  - Thermobrachium celere gen. nov., sp. nov., a rapidly growing thermophilic,
      alkalitolerant, and proteolytic obligate anaerobe.
AB  - More than 40 isolates of a novel, ubiquitous, proteolytic, moderately
      alkaliphilic, thermophilic obligate anaerobe were obtained from geothermally and
      anthropogenically heated environments and mesobiotic environments located on
      three continents. Whole-cell protein sodium dodecyl sulfate gel electrophoresis
      revealed that most of these organisms are very similar. Eight of the isolates
      were characterized in detail; this analysis included 16S ribosomal DNA sequence
      analysis. The cells of those organisms are (depending on the isolate) 0.5 to 0.8
      micron in diameter and 1.5 to 13 microns long, exhibit tumbling motility, and
      have a positive Gram stain reaction. The temperature range for growth is 43
      degrees to 75 degrees C (optimum temperature, 66 degrees C), and the pH range for
      growth is 5.4 to 9.5 (optimum pH, 8.2); the shortest doubling time is around 10
      min. Yeast extract is required for growth, and (depending on the strain) glucose,
      sucrose, fructose, galactose, and ribose are utilized. The fermentation products
      from glucose in the presence of yeast extract are CO2, H2, acetate, formate, and
      ethanol. The G + C content is 30 to 31 mol%. On the basis of these properties,
      which differentiate these strains from all alkalitolerant thermophiles described
      previously, and the results of a comparison of the 16S ribosomal DNA sequences of
      these organisms with previously described sequences, we propose that our isolates
      be placed in a single species of the new genus Thermobrachium; strain JW/YL-NZ35
      is the type strain of the the type species, Thermobrachium celere.

PMID- 8863433
TI  - Phenotypic and DNA relatedness between nematode symbionts and clinical strains of
      the genus Photorhabdus (Enterobacteriaceae).
AB  - Bacterial strains isolated from wide ranges of nematode hosts and geographic
      sources and strains isolated from human clinical specimens were used to assess
      the taxonomic structure of the genus Photorhabdus. The following two methods were
      used: DNA relatedness and phenotypic characterization. Analysis of the DNA
      relatedness data revealed that all of the strains studied were congeneric and
      that the genus Photorhabdus is, on the basis of DNA relatedness data, more
      homogeneous than the other genus of nematode-symbiotic bacteria, the genus
      Xenorhabdus. In contrast to previous reports, only two DNA relatedness groups
      were identified in the genus Photorhabdus. These groups corresponded to the
      symbiotic strains and the clinical strains. There appeared to be some subgroups
      within the symbiotic strain group on the basis of the interactions of the strains
      with nematodes, which corresponded to some extent with the DNA relatedness data.
      However, there were significant ambiguities in the DNA relatedness data, and this
      group could not be subdivided on the basis of DNA relatedness data or phenotypic
      data. The distinct functional differences within and between the DNA relatedness
      groups of symbiotic Photorhabdus strains indicated that there are biologically
      significant sub-groups within the genus Photorhabdus that cannot be defined at
      this time. Further investigation of the taxonomy of Photorhabdus by using
      different approaches and a suitably wide range of strains is recommended.
      However, it is clear that the clinical strains form a recognizable subgroup
      within the genus even though no formal subtaxon can be defined at this time.

PMID- 8863434
TI  - Description of chlorophenol-degrading Pseudomonas sp. strains KF1T, KF3, and NKF1
      as a new species of the genus Sphingomonas, Sphingomonas subarctica sp. nov.
AB  - Gram-negative polychlorophenol-degrading bacterial strains KF1T (T = type
      strain), KF3, and NKF1, which were described previously as Pseudomonas
      saccharophila strains, were studied by chemotaxonomic, genetic, and physiological
      methods and by electron microscopy and compared with selected xenobiotic compound
      degrading bacteria. These strains contained sphingolipids with d-18:0, d-20:1,
      and d-21:1 as the main dihydrosphingosines, ubiquinone 10 as the main respiratory
      quinone, and spermidine as the major polyamine, and the DNA G + C content was 66
      mol%. The cellular fatty acids included about 60% octadecenoic acid, 9% 2
      hydroxymyristic acid, 14% cis-9-hexadecenoic acid, and 10% hexadecanoic acid.
      These strains exhibited less than 97% 16S ribosomal DNA sequence similarity to
      all of the other taxa studied. In the DNA-DNA reassociation studies the highest
      levels of reassociation between these strains and previously described species
      were less than 40%. Thin sections of cells of strains KF1T, KF3, and NKF1 were
      examined by electron microscopy, and the results showed that the cells had
      peculiar concentrically arranged layered membranous blebs that extruded from the
      outer membrane, especially at the cell division points. On the basis of the
      results of this study, polychlorophenol-degrading strains KF1T, KF3, and NKF1 are
      considered members of a new species of the genus Sphingomonas, Sphingomonas
      subarctica. The polycyclic aromatic hydrocarbon-degrading organism Sphingomonas
      paucimobilis EPA 505 was closely related to Sphingomonas chlorophenolica as
      determined by chemotaxonomic, phylogenetic, and physiological criteria. The
      xenobiotic compound degraders Alcaligenes sp. strain A175 and Pseudomonas sp.
      strain BN6 were identified as members of species of the genus Sphingomonas.

PMID- 8863435
TI  - Sulfobacillus disulfidooxidans sp. nov., a new acidophilic, disulfide-oxidizing,
      gram-positive, spore-forming bacterium.
AB  - An acidophilic, disulfide-oxidizing, mesophilic, aerobic bacterium was isolated
      from wastewater sludge. The new organism is a gram-positive sporulated rod. It
      can use elemental sulfur and pyrite as sole energy sources and grows on organic
      substrates such as glutamate and glucose. It also grows on the following organic
      sulfur substrates: oxidized and reduced glutathione, cysteine, cystine, and
      dithio(bis)benzothiazole and clearly shows a preference for disulfide bond
      containing substrates. The optimal pH of growth is between 1.5 and 2.5, depending
      on the substrate used, and the growth temperature range varies from 4 to 40
      degrees C, with an optimal value at 35 degrees C. The G + C chromosomal DNA
      content was measured at 53 +/- 1 mol%. Phylogenetic analysis of 16S genes coding
      for rRNA sequences places the new isolate in the genus Sulfobacillus. In
      addition, unique phenotypic and physiologic characteristics and DNA homology
      values assign the isolate to a new species in the genus. Therefore, this new
      isolate has been named Sulfobacillus disulfidooxidans and has been assigned ATCC
      number 51911.

PMID- 8863436
TI  - Phylogenetic positions of Desulfofustis glycolicus gen. nov., sp. nov., and
      Syntrophobotulus glycolicus gen. nov., sp. nov., two new strict anaerobes growing
      with glycolic acid.
AB  - The glycolate-oxidizing, sulfate-reducing bacterium strain PerGlyS and the
      syntrophically glycolate-oxidizing bacterium strain FlGlyR were studied with
      respect to their phylogenetic relationships on the basis of in vitro
      amplification and direct sequencing of 16S rRNA-encoding DNA. Strain PerGlyS
      clustered with representatives of the delta subclass of the class Proteobacteria,
      close to "Desulforhopalus vacuolatus" but sufficiently distinct to preclude its
      assignment to this genus. These organisms, together with Desulfobulbus
      propionicus, represent a phylogenetic subgroup among members of the delta
      subclass of Proteobacteria. Strain FlGlyR was found to cluster with the gram
      positive bacteria with low-G + C DNA, and Desulfitobacterium dehalogenans and
      Desulfotomaculum orientis are its closest relatives. Other species of the genus
      Desulfotomaculum are phylogenetically only moderately closely related to these
      organisms. These results necessitate the establishment of new genera and species
      for these two strains. Strain PerGlyS was designated the type strain of
      Desulfofustis glycolicus gen. nov., sp. nov., and strain FlGlyR was designated
      the type strain of Syntrophobotulus glycolicus gen. nov., sp. nov.

PMID- 8863437
TI  - Aeropyrum pernix gen. nov., sp. nov., a novel aerobic hyperthermophilic archaeon
      growing at temperatures up to 100 degrees C.
AB  - A novel aerobic hyperthermophilic archaeon was isolated from a coastal solfataric
      vent at Kodakara-Jima Island, Japan. The new isolate, strain K1, is the first
      strictly aerobic organism growing at temperatures up to 100 degrees C. It grows
      optimally at 90 to 95 degrees C, pH 7.0, and a salinity of 3.5%. The cells are
      spherical shaped and 0.8 to 1.2 microns in diameter. Various proteinaceous
      complex compounds served as substrates during aerobic growth. Thiosulfate
      stimulates growth without producing H2S. The core lipids consist solely of C25
      isopranyl archaeol (glycerol diether). The G + C content of the genomic DNA is 67
      mol%. Phylogenetic analysis based on 16S rRNA sequence indicates that strain K1
      is a new member of Crenarchaeota. On the basis of our results, the name Aeropyrum
      pernix gen. nov., sp. nov. is proposed (type strain: K1; JCM 9820).

PMID- 8863438
TI  - Reassessment of the phylogenetic position of the bacterium associated with
      Whipple's disease and determination of the 16S-23S ribosomal intergenic spacer
      sequence.
AB  - Whipple's disease is a rare chronic illness associated with an unculturable
      bacterium that is constantly present in affected tissues. This bacterium was
      previously characterized at the molecular level by PCR and sequencing of the 16S
      rRNA gene. On the basis of 1,321 nucleotides of the sequence of its gene coding
      for 16S rRNA (16S rDNA), a phylogenetic relationship to the actinomycetes was
      established. In this study, we determined an almost complete 16S rDNA sequence
      (1,495 nucleotides), the 16S-23S ribosomal intergenic spacer sequence, and 200
      nucleotides of the 23S rRNA gene. The 16S rDNA sequence was compared with the
      large number of actinomycete sequences that have been added to the database since
      the original study. Phylogenetic analysis revealed a branching position as the
      deepest branch of the cluster comprising the actinomycetes with group B
      peptidoglycan between this group and the family Cellulomonadaceae. This provides
      additional information on the phylogenetic position of this bacterium and some
      clues as to its characteristics. The spacer region between the 16S and 23S rRNA
      genes is 294 nucleotides long and does not contain tRNA genes. As has been shown
      in other instances, the increased variability of the ribosomal intergenic spacer
      compared with the 16S rRNA gene makes it a potential target for use in the
      differentiation of strains of the bacterium associated with Whipple's disease.

PMID- 8863439
TI  - Phylogenetic relationships of the genera Acetobacterium and Eubacterium sensu
      stricto and reclassification of Eubacterium alactolyticum as Pseudoramibacter
      alactolyticus gen. nov., comb. nov.
AB  - 16S rRNA gene sequences of the type strains of the seven previously described
      Acetobacterium species were determined. The Acetobacterium species were found to
      form a tight phylogenetic cluster within the Clostridium subphylum of the gram
      positive bacteria. Within this subphylum these organisms belong to cluster XV as
      defined by Collins et al. (M.D. Collins, P.A. Lawson, A. Willems, J.J. Cordoba,
      J. Fernandez-Garayzabal, P. Garcia, J. Cai, H. Hippe, and J. A. E. Farrow, Int.
      J. Syst. Bacteriol. 44:812-826, 1994) together with Eubacterium alactolyticum
      barkeri, Eubacterium callanderi, and Eubacterium limosum. Our data indicate that
      Clostridium cluster XV consists of at least the following three genera: the genus
      Acetobacterium, the genus Eubacterium sensu stricto (comprising E. limosum, E.
      barkeri, and E. callanderi), and the genus Pseudoramibacter gen. nov., which is
      created for E. alactolyticum, which we reclassify as Pseudoramibacter
      alactolyticus comb. nov.

PMID- 8863440
TI  - The genus Nocardiopsis represents a phylogenetically coherent taxon and a
      distinct actinomycete lineage: proposal of Nocardiopsaceae fam. nov.
AB  - The genus Nocardiopsis was shown to be phylogenetically coherent and to represent
      a distinct lineage within the radiation of the order Actinomycetales. The closest
      relatives of the genus Nocardiopsis are members of the genera Actinomadura,
      Thermomonospora, Streptosporangium, and Microtetraspora. The intrageneric
      structure of the genus Nocardiopsis is shown to consist of a highly related
      species group containing Nocardiopsis dassonvillei, Nocardiopsis alborubida, and
      Nocardiopsis antarctica and a second group of less highly related species
      comprising Nocardiopsis alba subsp. alba, Nocardiopsis alba subsp. prasina, and
      Nocardiopsis listeri. Nocardiopsis lucentensis occupies a position intermediate
      between the two species groups. The results of a 16S ribosomal DNA sequence
      analysis are generally consistent with the available chemotaxonomic, phenotypic,
      and DNA-DNA hybridization data. The phylogenetic position and the morpho- and
      chemotaxonomic properties of Nocardiopsis species support the creation of a
      family for the genus Nocardiopsis, Nocardiopsaceae fam. nov.

PMID- 8863441
TI  - Phylogeny of some mycoplasmas from ruminants based on 16S rRNA sequences and
      definition of a new cluster within the hominis group.
AB  - Almost complete (> 96%) 16S rRNA sequences from nine ruminant mycoplasmas have
      been determined by solid-phase DNA sequencing. Polymorphisms were found in four
      of the 16S rRNA sequences, which indicated the existence of two different rRNA
      operons. Seven polymorphisms were found in Mycoplasma agalatiae, three were found
      in Mycoplasma bovis, one was found in Mycoplasma alkalescens, and one was found
      in Mycoplasma bovirhinis. The sequence data were used for construction of
      phylogenetic trees. All but one of the ruminant mycoplasmas sequenced in this
      work clustered in the hominis group. A close relationship was found between M.
      agalactiae and M. bovis, with a 99% nucleotide similarity between their 16S rRNA
      sequences. They were also found to be members of the Mycoplasma lipophilum
      cluster of the hominis group. Furthermore, the 16S rRNA comparisons showed that
      Mycoplasma alkalescens and Mycoplasma canadense are closely related (> 98.5%),
      and these species were found to cluster in the Mycoplasma hominis cluster of the
      hominis group. Interestingly, M. bovirhinis grouped in a new phylogenetic cluster
      of the hominis group. The new cluster, which was supported by bootstrap
      percentage values, signature nucleotide analysis, and higher-order structural
      elements, was named the Mycoplasma synoviae cluster. Mycoplasma bovoculi,
      Mycoplasma conjunctivae, and Mycoplasma ovipneumoniae clustered in the Mycoplasma
      neurolyticum cluster of the hominis group. Mycoplasma alvi clustered with
      Mycoplasma pirum in the M. pneumoniae cluster of the pneumoniae group.

PMID- 8863442
TI  - Rhodothermus obamensis sp. nov., a modern lineage of extremely thermophilic
      marine bacteria.
AB  - A novel extremely thermophilic bacterium was isolated from a shallow marine
      hydrothermal vent environment (depth, 22 m) in Tachibana Bay, Nagasaki
      Prefecture, Japan. The cells of this organism were gram-negative rods. Growth
      occurred at temperatures between 50 and 85 degrees C (optimum temperature, 80
      degrees C; doubling time at optimum temperature, 90 min), at pH 5.5 and 9.0
      (optimum pH, 7.0), and in the presence of 1 and 5% NaCl (optimum NaCl
      concentration, 3%). The new isolate was an aerobic heterotroph which utilized the
      following compounds as sole energy and carbon sources: yeast extract, peptone,
      starch, casein, Casamino Acids, a variety of sugars, some carboxylic acids, and
      amino acids. As determined by a sequence analysis of the 16S rRNA, the new
      isolate belongs to the genus Rhodothermus and represents a modern lineage of
      extreme thermophiles within the domain Bacteria. On the basis of the
      physiological and molecular properties of the new isolate, we describe a new
      species, Rhodothermus obamensis. The type strain of R. obamensis is strain OKD7
      (= JCM 9785).

PMID- 8863443
TI  - Organization and phylogenetic interrelationships of genes encoding components of
      the botulinum toxin complex in proteolytic Clostridium botulinum types A, B, and
      F: evidence of chimeric sequences in the gene encoding the nontoxic
      nonhemagglutinin component.
AB  - The cluster of genes encoding components of the botulinum neurotoxin (BoNT)
      complex was mapped in proteolytic (group I) Clostridium botulinum strains
      encoding BoNT types A, B, and F. Two different arrangements of genes were found:
      type A strain 62A and type B strain NCTC 7273 have similar organizations of genes
      encoding BoNT, the nontoxic nonhemagglutinin component (NTNH), hemagglutinin
      components, and P-21; type F strain Langeland has genes encoding BoNT, NTNH, and
      P-21, and a previously unidentified open reading frame encoding a protein of 416
      amino acids. A group of type A strains typified by infant strain Kyoto-F, which
      is unlike type A strain 62A, lacks genes for hemagglutinin components and
      exhibits an organization similar to that of type F. Sequencing and pairwise
      analysis revealed the presence of possible chimeric sequences in some NTNH genes
      of proteolytic C. botulinum. Discordance in genealogical trees derived from
      different regions of the NTNH genes was observed which could be symptomatic of
      recombination and which may indicate that the NTNH gene represents a hot spot for
      such events within the cluster of genes encoding the BoNT complex. It is also
      evident that the phylogenetics of the NTNH gene, which is linked to the gene
      encoding BoNT, does not mirror the evolutionary history of the BoNT, upon which
      the C. botulinum species complex is defined and subdivided.

PMID- 8863444
TI  - Thermococcus fumicolans sp. nov., a new hyperthermophilic archaeon isolated from
      a deep-sea hydrothermal vent in the north Fiji Basin.
AB  - An extremely thermophilic archaeon, strain ST557T (T = type strain), was isolated
      from a deep-sea hydrothermal vent in the North Fiji Basin. This strain is a
      strictly anaerbic coccus whose cells are about 0.8 to 2 microns in diameter. The
      optimum temperature, pH and sea salt concentration for growth are 85 degrees C,
      8.5, and 20 to 40 g/liter, respectively. Strain ST557T grows preferentially in
      the presence of elemental sulfur on proteinaceous substrates and on a mixture of
      20 amino acids. It grows slowly on pyruvate and maltose. Growth is inhibited by
      rifampin. The DNA G + C content is 54 to 55 mol%. Sequencing of the 16S rRNA gene
      revealed that strain ST557T belongs to the genus Thermococcus. We propose that
      this organism should be placed in a new species, Thermococcus fumicolans.

PMID- 8863445
TI  - Eubacterium exiguum sp. nov., isolated from human oral lesions.
AB  - Eubacterium exiguum sp. nov. is the name proposed for organisms formerly
      described as Eubacterium group S strains and similar bacteria isolated from
      various types of oral lesions. This new species was established on the basis of
      the results of DNA-DNA hybridization experiments and DNA base composition
      determinations (G + C contents, 60 to 64 mol%). The results of an API ZYM
      analysis, Western blotting (immunoblotting) reactions, and phenotypic tests are
      also given. The type strain of E. exiguum is strain S-7.

PMID- 8863446
TI  - Isolation and characterization of a new gram-negative, acetone-degrading, nitrate
      reducing bacterium from soil, Paracoccus solventivorans sp. nov.
AB  - An acetone-degrading, nitrate-reducing, coccoid to rod-shaped bacterium, strain
      L1, was isolated from soil on the site of a natural gas company. Cells of the
      logarithmic growth phase reacted gram positive, while those of the stationary
      growth phase were gram negative. Single organisms were 0.4 to 0.5 by 0.9 to 1.5
      microns in size, nonmotile, and non-spore forming and had poly-beta
      hydroxybutyrate inclusions. The doubling time of strain L1 on acetone-CO2-nitrate
      at the optimal pH of 7 to 8 and the optimal temperature of 30 to 37 degrees C was
      12 h. More than 0.2% NaCl or 10 mM thiosulfate inhibited growth. For oxygen or
      nitrate respiration, acetone and a few organic chemicals were utilized as carbon
      sources whereas many others could not be used (for details, see Results).
      Bicarbonate (or CO2) was essential for growth on acetone but not for growth on
      acetoacetate. The growth yields for acetone-CO2 and acetoacetate were 28.3 and
      27.3 g/mol, respectively. With acetone as the carbon source, poly-beta
      hydroxybutyrate accounted for up to 40% of the cellular dry weight. The DNA of
      strain L1 had a G + C content of 68.5 mol% (as determined by high-performance
      liquid chromatography of nucleotides) or 70 mol% (as determined by the TM
      method). The sequence of the gene coding for the 16S rRNA led to the
      classification of strain L1 in the paracoccus group of the alpha subclass of the
      Proteobacteria. The new isolate is named Paracoccus solventivorans sp. nov. DSM
      6637.

PMID- 8863447
TI  - Thermosyntropha lipolytica gen. nov., sp. nov., a lipolytic, anaerobic,
      alkalitolerant, thermophilic bacterium utilizing short- and long-chain fatty
      acids in syntrophic coculture with a methanogenic archaeum.
AB  - Three strains of an anaerobic thermophilic organoheterotrophic lipolytic
      alkalitolerant bacterium, Thermosyntropha lipolytica gen. nov., sp. nov. (type
      strain JW/VS-265T; DSM 11003), were isolated from alkaline hot springs of Lake
      Bogoria (Kenya). The cells were nonmotile, non-spore forming, straight or
      slightly curved rods. At 60 degrees C the pH range for growth determined at 25
      degrees C [pH25 degrees C] was 7.15 to 9.5, with an optimum between 8.1 and 8.9
      (pH60 degrees C of 7.6 and 8.1). At a pH25 degrees C of 8.5 the temperature range
      for growth was from 52 to 70 degrees C, with an optimum between 60 and 66 degrees
      C. The shortest doubling time was around 1 h. In pure culture the bacterium grew
      in a mineral base medium supplemented with yeast extract, tryptone, Casamino
      Acids, betaine, and crotonate as carbon sources, producing acetate as a major
      product and constitutively a lipase. During growth in the presence of olive oil,
      free long-chain fatty acids were accumulated in the medium but the pure culture
      could not utilize olive oil, triacylglycerols, short- and long-chain fatty acids,
      and glycerol for growth. In syntrophic coculture (Methanobacterium strain JW/VS
      M29) the lipolytic bacteria grew on triacylglycerols and linear saturated and
      unsaturated fatty acids with 4 to 18 carbon atoms, but glycerol was not utilized.
      Fatty acids with even numbers of carbon atoms were degraded to acetate and
      methane, while from odd-numbered fatty acids 1 mol of propionate per mol of fatty
      acid was additionally formed. 16S rDNA sequence analysis identified
      Syntrophospora and Syntrophomonas spp. as closest phylogenetic neighbors.

PMID- 8863448
TI  - DNA relatedness among Pseudomonas strains isolated from natural mineral waters
      and proposal of Pseudomonas veronii sp. nov.
AB  - The taxonomic position of eight strains isolated from mineral water and
      previously grouped in the authentic pseudomonads on the basis of a phenotypic
      analysis (cluster Ib of M. Elomari, L. Coroler, D. Izard, and H. Leclerc [J.
      Appl. Bacteriol. 78:71-81, 1995]) has been further studied by DNA-DNA
      hybridizations. Using the S1 nuclease method at 60 degrees C and labeled
      reference DNA from a representative strain, CFML 92-134, we showed that members
      of cluster Ib constituted a homogeneous group with a relative binding ratio of
      greater than 80% and changes in melting temperature of less than 1 degree C. With
      a total of 67 strains representing known or partially characterized species of
      the genus Pseudomonas, only 4 to 47% DNA hybridization and changes in melting
      temperature of between 8 and 20 degrees C were found, the highest hybridization
      values being measured with members of the saprophytic fluorescent pseudomonads.
      Since cluster Ib could also be clearly differentiated from members of the latter
      group and from other phenotypic clusters containing isolates from mineral water,
      we designated the Ib strains members of a new Pseudomonas species for which the
      name Pseudomonas veronii sp. nov. has been proposed. Members of this species grew
      on alpha-aminobutyrate, sucrose, butyrate, isobutyrate, erythritol, L-tryptophan,
      and trigonelline as sole sources of carbon and energy. The average G+C content of
      the DNA of the eight strains of P. veronii was 61.5 +/- 0.5 mol%. The type strain
      is CFML 92-134T (CIP 104663T), with a G+C content of 61 mol%. The clinical
      significance of P. veronii is unknown.

PMID- 8863449
TI  - Clostridium ultunense sp. nov., a mesophilic bacterium oxidizing acetate in
      syntrophic association with a hydrogenotrophic methanogenic bacterium.
AB  - A syntrophic acetate-oxidizing bacterium, strain BST (T = type strain), was
      isolated from a previously described mesophilic triculture that was able to
      syntrophically oxidize acetate and form methane in stoichiometric amounts. Strain
      BST was isolated with substrates typically utilized by homoacetogenic bacteria.
      Strain BST was a spore-forming, gram-positive, rod-shaped organism which utilized
      formate, glucose, ethylene glycol, cysteine, betaine, and pyruvate. Acetate and
      sometimes formate were the main fermentation products. Small amounts of alanine
      were also produced from glucose, betaine, and cysteine. Strain BST grew optimally
      at 37 degrees C and pH 7. The G+C content of the DNA of strain BST was 32 mol%. A
      16S rRNA sequence analysis revealed that strain BST was a member of a new species
      of the genus Clostridium. We propose the name Clostridium ultunense for this
      organism; strain BS is the type strain of C. ultunense.

PMID- 8863450
TI  - Chrysiogenes arsenatis gen. nov., sp. nov., a new arsenate-respiring bacterium
      isolated from gold mine wastewater.
AB  - A new strictly anaerobic bacterium (strain BAL-1T) has been isolated from a reed
      bed at Ballarat Goldfields in Australia. The organism grew by reducing arsenate
      [As(V)] to arsenite [As(III)], using acetate as the electron donor and carbon
      source; acetate alone did not support growth. When BAL-1T was grown with arsenate
      as the terminal electron acceptor, acetate could be replaced by pyruvate, L- and
      D-lactate, succinate, malate, and fumarate but not by H2, formate, citrate,
      glutamate, other amino acids, sugars, or benzoate. When acetate was the electron
      donor, arsenate could be replaced by nitrate or nitrite but not by sulfate,
      thiosulfate, or iron oxide. Nitrate was reduced to ammonia via nitrite. The
      doubling time for growth on acetate (5 mM) plus arsenate (5 mM) or nitrate (5 mM)
      was 4 h. The G+C content of the DNA is 49 mol%. The 16S rRNA sequence data for
      the organism support the hypothesis that this organism is phylogenetically unique
      and at present is the first representative of a new deeply branching lineage of
      the Bacteria. This organism is described as Chrysiogenes arsenatis gen. nov., sp.
      nov.

PMID- 8863451
TI  - Lactobacillus curvatus subsp. curvatus subsp. nov. and Lactobacillus curvatus
      subsp. melibiosus subsp. nov. and Lactobacillus sake subsp. sake subsp. nov. and
      Lactobacillus sake subsp. carnosus subsp. nov., new subspecies of Lactobacillus
      curvatus Abo-Elnaga and Kandler 1965 and Lactobacillus sake Katagiri, Kitahara,
      and Fukami 1934 (Klein et al. 1996, emended descriptions), respectively.
AB  - Lactobacillus curvatus and Lactobacillus sake are each genetically homogeneous
      species, as indicated by the high levels of DNA homology (> or = 76%) exhibited
      by strains of these taxa. However, the results of a numerical analysis of total
      soluble cell protein patterns and biochemical test data revealed that there are
      two phenotypic subgroups within L, curvatus and two phenotypic subgroups within
      L. sake. The overall randomly amplified polymorphic DNA (RAPD)-PCR band patterns
      obtained for the majority of L. curvatus strains corresponded well to the pattern
      obtained for the type strain of L. curvatus (strain DSM 20019). However, six
      strains of L. curvatus had different, but similar, RAPD-PCR profiles and grouped
      in a separate genetic cluster, which was linked to one of the clusters of L. sake
      strains. On the basis of these results, differences in biochemical and
      physiological characteristics, and total soluble cell protein profiles, we
      describe the subspecies L. curvatus subsp. curvatus subsp. nov. and L. curvatus
      subsp. melibiosus subsp. nov. for L. curvatus Abo-Elnaga and Kandler 1965 (Klein
      et al. 1996, emended description). Strains of L. sake grouped in two RAPD-PCR
      clusters, which was consistent with previous reports of phenotypic heterogeneity.
      Strains of Lactobacillus bavaricus, including type strain LMG 9844, clustered
      with the type strain of L. sake (strain NCFB 2714), indicating that these
      organisms belong to the same genetic group. We propose that strains of L. sake
      Katagiri, Kitahara, and Fukami 1934 (Klein et al. 1996, emended description)
      should be reclassified as members of L. sake subsp. sake subsp. nov. and L. sake
      subsp. carnosus subsp. nov. Strains of L. bavaricus are reclassified as members
      of L. sake subsp. sake, and the name L. bavaricus Stetter and Stetter 1980 is
      rejected.

PMID- 8863452
TI  - Determination of mycobacterial phylogeny on the basis of immunological
      relatedness of superoxide dismutases.
AB  - Sixteen strains of cultivable mycobacteria were grown in Sauton's medium, and
      Mycobacterium leprae was purified from armadillo liver. Cell extracts were
      prepared from log-phase growths of each of the cultivable mycobacterial strains.
      Superoxide dismutase (SOD) enzyme was purified from all cultivable mycobacterial
      strains included in the study, and antibodies against purified SOD enzyme were
      raised in rabbits. Immunological distances (ImDs) between these anti-SOD
      antibodies and SOD antigens were determined by a previously described
      immunoprecipitation method and by a recently developed enzyme-linked
      immunosorbent assay (ELISA) technique. The reciprocal ImDs among mycobacterial
      strains were constant, reproducible and consistent by these two methods. An
      evolutionary tree was constructed on the basis of estimated ImDs. Except for M.
      duvalii and M. terrae, slowly and rapidly growing mycobacterial species appeared
      to be separately grouped by this analysis. Rapid growers clustered into a group
      which is near that of some slow-growing mycobacteria. M. avium falls almost in
      the middle of the evolutionary tree and the position of M. leprae was found to be
      between those of M. avium and M. bovis BCG. Measurement of immunological
      relatedness of SODs provides an alternative system with which to study the
      taxonomical relatedness among mycobacteria.

PMID- 8863453
TI  - Phylogeny of Methanopyrus kandleri based on methyl coenzyme M reductase operons.
AB  - The mcrBDCGA operon that encodes methyl coenzyme M reductase (MR) in the
      hyperthermophile Methanopyrus kandleri was cloned and sequenced. The results of a
      phylogenetic analysis of the nine MR sequences now available support the position
      that M. kandleri is a separate methanogen lineage. As in other methanogens, the
      M. kandleri mcr operon is located immediately upstream of the mtrE gene, the
      promoter-proximal gene in an operon that encodes the N5
      methyltetrahydromethanopterin:coenzyme M methyltransferase that catalyzes the
      step preceding the MR-catalyzed reaction in methanogenesis. In contrast to other
      methanogens and hyperthermophilic members of the Archaea, CG dinucleotides and CG
      containing codons occur frequently in M. kandleri DNA. The MR subunit-encoding
      genes are preceded by sequences consistent with ribosome binding sites,
      indicating that mRNA-rRNA base pairing can still direct translation initiation in
      cells growing at temperatures above 100 degrees C.

PMID- 8863454
TI  - Phylogenetic positions of Clostridium chauvoei and Clostridium septicum based on
      16S rRNA gene sequences.
AB  - The sequences of the 16S rRNA genes (rrs genes) of Clostridium chauvoei, the
      causative agent of blackleg in cattle, and the phenotypically related organism
      Clostridium septicum were determined. After amplification of 1,507-bp PCR
      fragments from the corresponding rrs genes, the sequences were determined in a
      single round of sequencing by using conserved region primers. A sequence
      similarity analysis of the sequences revealed the close phylogenetic relationship
      of C. chauvoei and C. septicum in Clostridium cluster I (M. D. Collins, P. A.
      Lawson, A. Willems, J. J. Cordoba, J. Fernandez-Garayzabal, P. Garcia, J. Cai, H.
      Hippe, and J. A. E. Farrow, Int. J. Syst. Bacteriol. 44:812-826, 1994), which
      includes Clostridium carnis, Clostridium perfringens, Clostridium botulinum, and
      Clostridium tetani. We found that 99.3% of the nucleotides in the genes of C.
      chauvoei and C. septicum are identical.

PMID- 8863455
TI  - Phylogenetic relationships of the porcine mycoplasmas Mycoplasma hyosynoviae and
      Mycoplasma hyopharyngis.
AB  - The phylogenetic positions of the porcine mycoplasmas Mycoplasma hyosynoviae and
      Mycoplasma hyopharyngis were determined by using PCR-amplified 16S rRNA gene
      sequences. M. hyosynoviae is a member of the Mycoplasma hominis group, while M.
      hyopharyngis belongs to the Mycoplasma fermentans group of mollicutes. Neither
      species is closely related to previously characterized porcine mycoplasmas
      belonging to the Mycoplasma hyorhinis group.

PMID- 8863456
TI  - Ureaplasma gallorale, an isolate from chickens, is most closely related to the
      human isolate, U. urealyticum.
AB  - Ureaplasma gallorale is a urease-containing mycoplasma (a member of the
      Mollicutes) which is pathogenic for chickens, from which it was originally
      isolated. We amplified the 16S rRNA gene of this bacterium and then cloned and
      sequenced the amplicon. A phylogenetic analysis based on an alignment of the 16S
      rRNA sequences of U. gallorale and several other Ureaplasma species revealed that
      U. gallorale is more closely related to Ureaplasma urealyticum than to other
      Ureaplasma species.

PMID- 8863457
TI  - Self-care behaviors in insulin-dependent diabetes: evaluative tools and their
      associations with glycemic control.
AB  - Clarified the relationships between self-care behaviors and illness-specific
      outcomes in approximately 270 youths with IDDM. Youths were assessed at three
      points in time using a semistructured interview measure and multiple indices of
      dietary intake and physical activity with two different methodologies (i.e.,
      recalls, logs). Glycemic control was most strongly related to the semistructured
      Self-Care Adherence Interview (SCAI); and second to the overall quality of the
      youth's dietary intake. The SCAI also predicted glycemic control over time.
      Physical activity levels and specific nutritional components from the logs and
      recalls were generally unrelated to glycemic control.

PMID- 8863458
TI  - Development and evaluation of a measure of concerns related to raising a child
      with a physical disability.
AB  - Developed a measure of perceived disability-related stress, the Parents of
      Children with Disabilities Inventory (PCDI). A content analysis of concerns
      expressed by mothers identified four primary domains: Medical and Legal Concerns,
      Concerns for the Child, Concerns for the Family, and Concerns for the Self. Item
      analysis performed on an initial item pool administered to 48 mothers recruited
      from area spina bifida and cerebral palsy clinics identified 40 items for further
      investigation. Psychometric evaluation of this final version was, performed based
      on additional data collected from 63 mothers from the same clinics. The
      organization and reliability of the PCDI were confirmed through traditional
      measures of internal consistency and test-retest reliability over a 2-month
      interval. Preliminary support for the construct validity of the PCDI was provided
      through the confirmation of several hypothesized relationships. Scores on the
      PCDI were significantly related to maternal mental and physical health. Concerns
      for the Self scale made a significant unique contribution to these prediction
      models. Findings provide preliminary support for the PCDI being an appropriate
      and informative measure of perceived disability-related stress to be used with
      mothers of children with physical disabilities.

PMID- 8863459
TI  - Brief report: the assessment of posttraumatic stress disorder in pediatric cancer
      patients and survivors.
AB  - Investigated the incidence and severity of Posttraumatic Stress Disorder (PTSD)
      in childhood cancer using informant methodology. The parents of pediatric cancer
      patients (n = 30) and off-treatment survivors (n = 42) completed a modified
      version of the Posttraumatic Stress Disorder Symptom Scale (PSS) on their
      children (M age = 8.8: SD = 4.0), in addition to the Child Behavior Checklist
      (CBCL) and the Personality Inventory for Children (PIC). Medical treatment and
      demographic data were also collected for each child. The only variables that
      significantly identified the presence of symptoms of PTSD were being on treatment
      at the time of the evaluation or in the preparatory phase prior to bone marrow
      transplantation and not having received cranial irradiation. Results indicate
      that a full constellation of PTSD symptoms can occur in children over the course
      of cancer treatment. Within the off-treatment pediatric cancer survivors,
      however, the incidence of PTSD was no greater than epidemiological estimates from
      the general population. The concurrent validity of the PSS received support, and
      the results, while preliminary, suggest that extended periods of medical trauma
      during which emotional support is present may not excessively predispose children
      to PTSD.

PMID- 8863460
TI  - Involving children and adolescents in medical decision making: developmental and
      clinical considerations.
AB  - Outlined the issues in informed consent, as well as goals for involving children
      and adolescents in decisions regarding their own medical treatment. This paper
      reviews the developmental and clinical considerations, and provides
      recommendations, for determining particular children's level of involvement.
      Finally, there are distinct roles for pediatric psychologists in this process,
      which are described. As medical treatment becomes increasingly sophisticated,
      there is an obligation for pediatric psychologists to appreciate the ethical and
      clinical issues in medical decision making for families.

PMID- 8863461
TI  - A content analysis of safety behaviors of television characters: implications for
      children's safety and injury.
AB  - Examined frequency and characteristics of safety behaviors in television programs
      popular with child audiences. A sample of 52 programs was coded for safety event
      location, demographic characteristics of safety models, social and physical
      contexts of safety events, and successful or unsuccessful outcomes of safety
      behaviors. Results indicate an overall rate of 13 safety behaviors per hour, with
      hour half of all safety behaviors located in commercial advertisements. Most
      safety behaviors were performed by made adult characters, had limited relevance
      for children, and were not associated with either positive or negative outcomes.
      Findings are discussed in terms of their relevance for observational learning of
      safety behaviors by child viewers.

PMID- 8863462
TI  - Adjustment in childhood brain tumor survival: child, mother, and teacher report.
AB  - Examined the adjustment of 6- to 18-year-old children and adolescents (n = 38) 2
      to 5 years postdiagnosis of brain tumor with respect to standardized measures of
      anxiety and depression; self-perceptions; and adaptive living skills. Child,
      mother, and teacher report data were used. Maternal adjustment (anxiety and
      depression, parenting stress) was also assessed. Children and adolescents
      surviving brain tumors reported themselves to be generally within the normal
      range. However, maternal ratings of social problems were higher than normative
      scores and significantly lower than norms on social problems, scholastic
      competence, and communication skills. Teacher ratings on the Teacher Rating Form
      were all within normal limits. Maternal adjustment measures were within the
      normal range, although the Parent-Child Dysfunctional Interaction subscale of the
      Parenting Stress index was elevated. No differences in scores were found between
      children in regular and special education, or between children who had received
      radiation and those who did not. This sample of survivors of pediatric brain
      tumors and their mothers had relatively mild problems in adjustment, supporting a
      competency-based view of the adaptation of pediatric patients and their families.

PMID- 8863463
TI  - Parents of children with cancer: a longitudinal study of emotional distress,
      coping style, and marital adjustment two and twenty months after diagnosis.
AB  - Evaluated emotional distress, coping style, and marital adjustment in 84 parents
      (42 couples) of children with cancer 2 months after diagnosis and again about 20
      months after diagnosis. As expected, mothers' mean state anxiety and trait
      anxiety scores decreased to near normal levels over time. Fathers' scores were
      lower initially and did not change. Neither mothers' nor fathers' mean marital
      adjustment scores changed over time. Marital adjustment at treatment follow-up
      was predicted by depression and the spouse's marital satisfaction in mothers, and
      depression, child health status, and spouse's marital satisfaction in fathers. In
      contrast to findings obtained 2 months after diagnosis, coping style was not
      related to marital adjustment at follow-up. Results are discussed in terms of
      possible gender differences in the role of social support in marital adjustment
      and the stability versus situational specificity of coping styles.

PMID- 8863464
TI  - Intuitive theories of human immunodeficiency virus transmission: their
      development and implications.
AB  - Explored the use of cluster analysis to characterize the development of intuitive
      theories of HIV transmission and examined relationships between children's
      theories and their attitudes regarding AIDS. In Study 1, analyses of interviews
      with 188 children and adolescents led to the identification of three relatively
      immature theories (undifferentiated thinking in which anything can cause AIDS,
      uncertainty about its causes, and a hybrid theory emphasizing germs as well as
      any form of drug use) and two relatively mature ones (both emphasizing true AIDS
      risk factors but differing in their understanding of blood exchange as a cause).
      Unwillingness to interact with persons with AIDS and worry about AIDS decreased
      with age and the former in particular was most closely associated with the belief
      that AIDS is spread through casual contact. In Study 2, analyses of data from a
      largely Mexican American sample of 306 third, fifth, and seventh graders yielded
      largely similar findings despite use of different risk factor subscales. Overall,
      the intuitive theories approach and the use of cluster analysis in its service
      appear to be promising ways of assessing children's knowledge of disease so that
      appropriate interventions for different subgroups of children can be designed.

PMID- 8863465
TI  - Commentary: pitfalls in the use of brief screening measures of coping.

PMID- 8863466
TI  - Commentary: systems theory orientation and clinical practice: a survey of
      pediatric psychologists.

PMID- 8863467
TI  - Retinoids and the visual process.

PMID- 8863468
TI  - Photochemical and photophysical studies of 3-amino-6-iodoacridine and the
      inactivation of lambda phage.
AB  - The photochemistry and photophysics of 3-amino-6-iodoacridine (Acr-I) was
      studied. Photolysis (350 nm) of Acr-I (free base) generates products consistent
      with a free radical intermediate in methanol, benzene and carbon tetrachloride.
      The Acr-I hydrochloride is shown to bind to calf thymus DNA and to the self
      complementary dinucleotide cytidylyl-(3'-5')-guanosine (CpG) miniduplex in a
      manner similar to that of proflavine (Acr-NH2), a known DNA intercalator. The Acr
      I is shown to more efficiently nick supercoiled plasmid DNA pBR322 upon 350 nm or
      420 nm photolysis than Acr-NH2. The efficiency of Acr-I-sensitized DNA nicking is
      not oxygen dependent. Photolysis of the Acr-I/(CpG)2 complex leads to cleavage of
      the dinucleotide and to cytidine base release by selective damage to a specific
      ribose moiety. Dinucleotide cleavage occurs equally well in the presence or
      absence of oxygen, thereby eliminating a singlet oxygen- or peroxyl radical
      mediated process. Photolysis of Acr-I in the presence of a mononucleotide (GMP)
      or a non-self-complementary dinucleotide (uridylyl-[3'-5']-cytidine-UpC) does not
      lead to fragmentation and base release. Similarly, photolysis of the Acr
      NH2/(CpG)2 complex does not lead to fragmentation and base release. The data
      indicate that photolysis of an iodinated intercalator bound to CpG or plasmid DNA
      generates an intercalated aryl radical and that the reactive intermediate
      initiates a sequence of reactions that efficiently nick nucleic acids. The
      inactivation of lambda phage sensitized by Acr-I with UV (350 nm) light is oxygen
      independent but with visible (420 nm) light is strongly oxygen dependent. The Acr
      I fluoresces more intensely when excited at 446 than at 376 nm. Thus, UV
      photolysis may lead to C-I bond homolysis and free radical formation, a process
      that is not energetically feasible with visible light. The results demonstrate
      the difficulty of extrapolating model studies involving simple molecules and DNA
      to understanding the mechanism of viral inactivation with a particular
      sensitizer.

PMID- 8863469
TI  - Two-color two-photon excitation of fluorescence.
AB  - We report the observation of two-photon excitation of an organic fluorophore with
      two different wavelengths, a phenomenon we refer to as two-color two-photon
      (2C2P) excitation. Ultraviolet emission of p-terphenyl at 340 nm was observed
      when the sample was illuminated with both 375 and 750 nm pulses from a picosecond
      dye laser. The emission of p-terphenyl was about 100-fold and more than 1000-fold
      less for illumination at only 375 or 750 nm, respectively. Observation of the
      2C2P signal required temporal and spatial overlap of the 375 and 750 nm pulses.
      The amplitude of the signal depended on the polarization of each beam. 2C2P
      excitation can have applications in fluorescence microscopy and elsewhere when
      spatially localized excitation is desirable.

PMID- 8863470
TI  - On the possibility of evanescent wave excitation distal from a solid-liquid
      interface using light quenching.
AB  - Evanescent wave illumination with total internal reflection is often used to
      provide excitation near a quartz-water interface. We now show that evanescent
      illumination at one wavelength and incident angle, coupled with light quenching
      at a second wavelength and incident angle, can be used for selective excitation
      of fluorophores located up to 5000 A into the aqueous phase. The displacement of
      the fluorophore population from the solid-liquid interface depends on the angles
      of incidence of the excitation and quenching beams and the optical power of the
      quenching beam. Light quenching with an evanescent wave was demonstrated to be
      experimentally possible using Pyridine2 and a light-quenching wavelength of 736
      nm. The use of combined evanescent wave excitation and evanescent wave quenching
      could provide selective excitation of fluorophores in the cytoplasmic region of
      cells and may provide improved response times for optical sensors based on
      evanescent excitation.

PMID- 8863471
TI  - Ultraviolet B wavelength dependence for the regulation of two major matrix
      metalloproteinases and their inhibitor TIMP-1 in human dermal fibroblasts.
AB  - The wavelength dependence for the regulation of two major matrix
      metalloproteinases, interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3),
      and their major inhibitor, tissue inhibitor of metalloproteinases (TIMP-1), was
      studied in human dermal fibroblasts in vitro. Monochromatic irradiation at 302,
      307, 312 and 317 nm with intensities ranging from 20 to 300 J/m2 increased MMP-1
      and MMP-3 mRNA steady-state levels and the secretion of the corresponding
      proteins up to 4.4-fold, whereas almost no increase was observed at wavelengths <
      290 nm. In contrast, the synthesis of TIMP-1 increased only marginally. This
      imbalance may contribute to the severe connective tissue damage related to
      photoaging of the skin. The wavelengths responsible for MMP-1 and MMP-3 induction
      reported here are distinct from the absorption spectrum of DNA and are different
      from results previously reported in the literature. Importantly, they overlap
      with wavelengths whose intensity is predicted to increase on the earth's surface
      upon ozone depletion. Intensities and particular wavelengths used in our studies
      in vitro can be absorbed readily by fibroblasts within the skin in vivo and,
      thus, are relevant for risk assessment and development of protective agents.

PMID- 8863472
TI  - Photodynamic therapy with a diode laser for implanted fibrosarcoma in mice
      employing mono-L-aspartyl chlorin E6.
AB  - The authors performed photodynamic therapy (PDT), avoiding any hyperthermic
      effects, using a newly developed diode laser and photosensitizer, mono-L-aspartyl
      chlorin e6 (NPe6), of Meth-A fibrosarcoma implanted in mice and achieved tumor
      therapeutic benefit. The photodynamic light treatment was performed 5 h following
      the photosensitizer administration. With 5.0 mg/kg NPe6 and light doses of 50,
      100, 150 and 200 J/cm2, the tumor cure rates were 20, 50, 70 and 90%,
      respectively. With 100 J/cm2 laser exposure and NPe6 doses of 1.25, 2.5, 5.0, 7.5
      and 10.0 mg/kg, the tumor cure rates were 0, 20, 50, 70 and 90%, respectively. A
      charge-coupled device (CCD) camera system was employed to measure the NPe6
      fluorescence intensity correlating with the residual amount of the
      photosensitizer at deferent depth from the tumor surface. The ratios of the NPe6
      fluorescence intensity at 3 mm from the tumor surface following 50, 100, 150 and
      200 J/cm2 laser exposure to no laser exposure were 0.73, 0.36, 0.22 and 0.16,
      respectively. With samples sectioned at 1 mm depth, after 50 J/cm2 and the same
      photosensitizer dose (5 mg/kg) this ratio was 0.19. These results suggest that a
      certain increase in the tumor tissue level of NPe6 and a certain increase of
      laser light dose reaching deeper layer of tumor caused an increase in percent
      cure. In addition, the effectiveness of PDT depends on the total laser dose
      reaching deeper layers of tumors. Furthermore, the effectiveness of PDT tends to
      correlate with the amount of NPe6 photobleaching by PDT.

PMID- 8863473
TI  - Detection of early stages of carcinogenesis in adenomas of murine lung by 5
      aminolevulinic acid-induced protoporphyrin IX fluorescence.
AB  - Administration of the heme precursor 5-aminolevulinic acid (ALA) leads to the
      selective accumulation of the photosensitizer protoporphyrin IX (PpIX) in certain
      types of normal and abnormal tissues. This phenomenon has been exploited
      clinically for detection and treatment of a variety of malignant and nonmalignant
      lesions. The present preclinical study examined the specificity of ALA-induced
      porphyrin fluorescence in chemically induced murine lung tumors in vivo. During
      the early stages of tumorigenesis, ALA-induced PpIX fluorescence developed in
      hyperplastic tissues in the lung and later in early lung tumor foci. In early
      tumor foci, maximum PpIX fluorescence occurred 2 h after the administration of
      ALA and returned to background levels after 4 h. There was approximately a 20
      fold difference in PpIX fluorescence intensity between tumor foci and the
      adjacent normal tissue. The specificity of ALA-induced fluorescence for
      hyperplastic tissues and benign tumors in lung during tumorigenesis suggests a
      possible use for this fluorochrome in the detection of premalignant alterations
      in the lung by fluorescence endoscopy. Two non-small cell lung cancer cell lines
      developed ALA-induced PpIX fluorescence in vitro. These lines exhibited a light
      dose-dependent phototoxic response to ALA photodynamic therapy (PDT) in vitro.
      Because PpIX is a clinically effective photosensitizer for a wide variety of
      malignancies, these results support the possible use of ALA-induced PpIX PDT for
      lung cancer.

PMID- 8863474
TI  - Inactivation of photosensitizing merocyanine dyes by plasma, serum and serum
      components.
AB  - Merocyanine dyes with an oxygen in the electron donor heterocycle were rapidly
      degraded by plasma, serum and serum components. Replacement of the oxygen by a
      sulfur or selenium atom rendered the dyes refractory to degradation. The
      degradation of labile merocyanine dyes was temperature dependent and oxygen
      independent. The plasma component that was responsible for the degradation of
      merocyanine dyes was sensitive to heat and detergent, suggesting an enzymatic
      process. The identification of the structural requirements for
      sensitivity/resistance to degradation provides the experimenter with a simple
      means to manipulate the stability of merocyanines in high serum or plasma
      environments and may expand the clinical utility of merocyanine photosensitizers
      beyond their traditional role in the extracorporeal purging of bone marrow
      grafts.

PMID- 8863475
TI  - Mexoryl SX protects against solar-simulated UVR-induced photocarcinogenesis in
      mice.
AB  - The aim of this study was to determine, for regulatory purposes, the potential of
      Mexoryl SX, a broad UVA absorber that also absorbs to some extent in the UVB, to
      modify the UV radiation (UVR)-induced murine skin tumor development and growth.
      Skh-hr1 mice were exposed to solar-simulated UVR 5 days per week for 40 weeks.
      Two control groups were irradiated without topical application, three groups
      received a sunscreen preparation containing either the UVA absorber, Mexoryl SX
      at 5 or 10% concentration, or a filter that absorbs principally in the UVB, 2
      ethylhexyl-p-methoxycinnamate (2-EHMC) at 5% concentration, introduced as a
      comparator test article. Sunscreen application was performed before UVR exposure
      3 days per week and after UVR exposure on the other 2 days (consistent with the
      design of a standard photocarcinogenesis safety test). Two different weekly UVR
      doses were administrated: the lower dose was given to one group of unprotected
      animals, whereas the higher dose was administrated to the other unprotected group
      and to the three sunscreen-treated groups. The two UVR control groups
      demonstrated a UVR-dependent response for cumulative tumor prevalence, tumor
      yield and median latent period. Neither concentration of Mexoryl SX increased the
      probability of tumor development; consistent with the principles for safety
      testing, this provides evidence in that it is safe for use in sunlight. Although
      this study was explicitly designed as a safety test, the results also provide
      some clues about the efficacy of Mexoryl SX in decreasing the probability of
      tumor development. Topical administration of Mexoryl SX, at both concentrations,
      resulted in a 6 week delay in the median latent period compared to high UVR
      controls, whereas 5% 2-EHMC delayed the median latent periods only by 2 weeks.
      Tumor prevalence and yield show the same efficacy differences between the two
      sunscreen ingredients. Tumor protection factors were calculated from these
      results and found to be equal to 2.4 for the two preparations containing Mexoryl
      SX and to 1.3 for the 5% 2-EHMC preparation. These findings illustrate the
      efficacy of Mexoryl SX in preventing UVR-induced carcinogenesis.

PMID- 8863476
TI  - Unsymmetrically substituted benzonaphthoporphyrazines: a new class of cationic
      photosensitizers for the photodynamic therapy of cancer.
AB  - Unsymmetrical zinc(II) complexes of benzonaphthoporphyrazines 5a-12a bearing
      between one and eight pyridyloxy substituents are synthesized by statistical
      tetramerization of 6-(1,1-dimethylethyl)-2,3-naphthalenedicarbonitrile (1) with 4
      (3-pyridyloxy)- or 4,5-bis-(3-pyridyloxy)-1,2-benzenedicarbonitrile (2, 3).
      Methylation of 5a-12a leads to the catianic pyridyloxybenzonaphthoporphyrazines
      5b-12b having between one to eight positive charges. The Q-band transition in the
      visible spectra exhibits a bathochromic shift from 680 to 760 nm dependent upon
      the number of annelated naphthalene rings. The singlet oxygen quantum yields of
      the benzonaphthoporphyrazines determined by the dye-sensitized photooxidation of
      1,3-diphenylisobenzofurane is surprisingly high (in the range of zinc
      phthalocyanine). The photooxidative stabilities of the photosensitizers described
      quantitatively by first-order kinetics decrease with the number of annelated
      naphtho groups. A linear correlation between the logarithm of the decomposition
      rate constant and the position of the highest occupied molecular orbital (HOMO)
      level of the photosensitizers is found. Destabilization of the HOMO leads to a
      decrease of the photostability. Due to their adjustable long wavelength
      absorption, their intramolecular polarity axis and their different
      hydrophilic/hydrophobic character, these novel compounds may be suitable
      photosensitizers for the photodynamic therapy of cancer.

PMID- 8863477
TI  - Measurement of tumor vascular damage in mice with 99mTc-MIBI following
      photodynamic therapy.
AB  - The clinical perfusion agent 99mTc-MIBI was used to monitor changes in tumor
      vascular perfusion (TVP) induced by Photofrin (PII)-mediated photodynamic therapy
      (PDT). BALB/c mice bearing an EMT-6 tumor on each hind thigh were given an
      intravenous injection of 1, 2 or 5 mg kg-1 PII. Twenty-four hours later, one
      tumor was illuminated (600-650 nm, 200 mW cm-2, 400 J cm-2) while the other
      served as a control. At various time intervals after PDT (0, 2 and 24 h) mice
      received an intravenous injection of 99mTc-hexakismethoxyisobutylisonitrile
      (MIBI) (0.18 MBq g-1) and were sacrificed 2 min later. The light-treated and the
      untreated tumors were then dissected, the radioactivity was counted and the
      percentage of the injected dose per gram of tumor (%ID g-1) was calculated as a
      measure of TVP. We observed that TVP is drug dose dependent, develops
      progressively with time post-PDT and is inversely related to PDT efficacy. Our
      data show that early tumor retention of 99mTc-MIBI is a simple method to assess
      TVP and vascular damage induced by PDT.

PMID- 8863478
TI  - Photodynamic therapy of human glioma (U87) in the nude rat.
AB  - We measured the response of normal brain and the human U87 glioma implanted in
      the brain of rats (n = 65) to photodynamic therapy (PDT) using Photofrin as the
      sensitizer. Normal brain and U87 tumor implanted within brain of athymic (nude)
      rats were subjected to PDT (12.5 mg/kg of Photofrin) at increasing optical energy
      doses (35 J/cm2, 140 J/cm2, 280 J/cm2) of 632 nm light. Photofrin concentration
      in tumor, brain adjacent to tumor and normal brain were measured in a separate
      population of rats. Twenty-four hours after PDT, the brains were removed,
      sectioned, stained with hematoxylin and eosin (H&E), and the volumes of the PDT
      induced lesion measured. Photofrin concentration in tumor greatly exceeded that
      of normal brain and brain adjacent to tumor (> 20x). Both normal brain and U87
      tumor exhibited superficial tissue damage with PDT at 35 J/cm2. However, both
      normal and tumor-implanted brain exhibited tissue damage with increasing optical
      dose. A heterogeneous pattern of pannecrosis along with a uniform volume of
      pannecrosis was detected in the tumor. In contrast, normal brain exhibited a
      uniform sharply demarcated volume of necrosis. Our data indicate that the U87
      human brain tumor model and the normal brain in the athymic rat are sensitive to
      PDT and Photofrin with an optical dose-dependent response to treatment.

PMID- 8863479
TI  - Photophysical and redox properties of a series of phthalocyanines: relation with
      their photodynamic activities on TF-1 and Daudi leukemic cells.
AB  - The photodynamic therapy (PDT) efficiency of five phthalocyanines, chloroaluminum
      phthalocyanine (AlPc), dichlorosilicon phthalocyanine (SiPc), bis(tri-n
      hexylsiloxy)silicon phthalocyanine (PcHEX), bis(triphenylsiloxy)silicon
      phthalocyanine (PcPHE) and nickel phthalocyanine (NiPc), was assessed on two
      leukemic cell lines TF-1 and erythroleukemic and B lymphoblastic cell lines,
      Daudi, respectively. AlPc showed the best photocytotoxicity leading to 0.008
      surviving fraction at 2 x 10(-9) M for TF-1 and 4 x 10(-9) M for Daudi. A1 5 x
      10(-7) M, SiPc and PcHEX induced a significant photokilling, whereas NiPc and
      PcPHE were inactive. Laser flash photolysis and photoredox properties of the
      phthalocyanines were investigated to try to relate these parameters with the
      biological effects. AlPc showed the longest triplet life-time: 484 microseconds
      in dimethyl sulfoxide/H2O. This value was increased up to 820 microseconds when
      AlPc was complexed with human serum albumin used as a membrane model. Such an
      enhancement was not observed with the silicon phthalocyanines. Upon irradiation,
      all the phthalocyanines generated singlet oxygen with 0.29-0.37 quantum yield
      values. The reduction potentials of the excited states obtained from measurement
      in the ground state and energy of the excited triplets show that AlPc is the best
      electron acceptor. The in vitro photocytotoxicity observed and the measured
      parameters are in agreement with a key role of electron transfer in PDT assays
      involving these phthalocyanines.

PMID- 8863480
TI  - Cervical precancer detection using a multivariate statistical algorithm based on
      laser-induced fluorescence spectra at multiple excitation wavelengths.
AB  - A portable fluorimeter was developed and utilized to acquire fluorescence spectra
      from 381 cervical sites in 95 patients at 337, 380 and 460 nm excitation
      immediately prior to colposcopy. A multivariate statistical algorithm was used to
      extract clinically useful information from tissue spectra acquired in vivo. Two
      full-parameter algorithms were developed using tissue fluorescence emission
      spectra at all three excitation wavelengths (161 excitation-emission wavelength
      pairs) for cervical precancer (squamous intraepithelial lesion [SIL]) detection:
      a screening algorithm that discriminates between SIL and non-SIL with a
      sensitivity of 82 +/- 1.4% and specificity of 68 +/- 0.0%, and a diagnostic
      algorithm that differentiates high-grade SIL from non-high-grade SIL with a
      sensitivity and specificity of 79 +/- 2% and 78 +/- 6%, respectively.
      Multivariate statistical analysis was also employed to reduce the number of
      fluorescence excitation-emission wavelength pairs needed to redevelop algorithms
      that demonstrate a minimum decrease in classification accuracy. Two reduced
      parameter algorithms that employ fluorescence intensities at only 15 excitation
      emission wavelength pairs were developed: the screening algorithm differentiates
      SIL from non-SIL with a sensitivity of 84 +/- 1.5% and specificity of 65 +/- 2%
      and the diagnostic algorithm discriminates high-grade SIL from non-high-grade SIL
      with a sensitivity and specificity of 78 +/- 0.7% and 74 +/- 2%, respectively.
      Both the full-parameter and reduced-parameter screening algorithms discriminate
      between SIL and non-SIL with a similar specificity (+/-5%) and a substantially
      improved sensitivity relative to Pap smear screening. A comparison of the full
      parameter and reduced-parameter diagnostic algorithms to colposcopy in expert
      hands indicates that all three have a very similar sensitivity and specificity
      for differentiating high-grade SIL from non-high-grade SIL.

PMID- 8863481
TI  - Catecholamine phenotyping: clues to the diagnosis, treatment, and pathophysiology
      of neurogenetic disorders.
AB  - One purpose of clinical neurochemistry has been to indicate "activities" of
      catecholamine systems, by assaying levels of the effector compounds or their
      metabolites in body fluids such as plasma, cerebrospinal fluid, urine, or
      microdialysate. This review discusses a new purpose: relating specific
      catecholaminergic phenotypes to neurogenetic disorders. Distinctive catecholamine
      patterns in several neurogenetic conditions reflect enzyme deficiencies as direct
      or indirect effects of gene mutations. These neurochemical patterns can provide
      potentially important clues to the diagnosis, treatment, and pathophysiology of
      neurogenetic disorders. Linking genetic abnormalities with molecular mechanisms
      and clinical manifestations of disease represents a useful new direction in
      clinical neurochemistry.

PMID- 8863482
TI  - The C terminal tail of the histamine H2 receptor contains positive and negative
      signals important for signal transduction and receptor down-regulation.
AB  - To examine the role of the C terminal tail in H2 receptor regulation, three
      cDNAs, encoding truncated histamine H2 receptor mutants (H2T295, H2T307, and
      H2T341), were constructed and stably transfected in Chinese hamster ovary (CHO)
      cells. The amino acids before position 307 appear to be necessary for proper
      receptor transport or folding, as no detectable H2 receptor binding of the H2T295
      was observed after transfection. Truncation of the C terminal tail by 51 amino
      acids (H2T307) did not affect the binding properties of H2 antagonists and
      histamine or histamine-induced signaling. Yet, removal of 17 amino acids
      generated a mutant receptor (H2T341), which was able to form a ternary complex
      but was unable to fully activate the Gs protein on histamine exposure. Agonist
      induced but not the cyclic AMP-dependent H2 receptor down-regulation was more
      profound for the H2T307 receptor, indicating that different structural elements
      of the H2 receptor protein are involved in the cyclic AMP-dependent and
      independent pathways of H2 receptor down-regulation. Taken together, in this
      study we identified regions in the C terminal tail of the H2 receptor that act as
      positive and/or negative signals in H2 receptor signaling and down-regulation.

PMID- 8863483
TI  - Inhibition of p42 and p44 mitogen-activated protein kinase activity by PD98059
      does not suppress nerve growth factor-induced survival of sympathetic neurones.
AB  - Nerve growth factor (NGF) induces persistent p42 and p44 mitogen-activated
      protein kinase (MAPK) activity in sympathetic neurones in parallel to its
      survival-promoting activity. To investigate whether these MAPK activities are
      necessary for NGF-induced survival, we have inhibited NGF-stimulated p42/p44 MAPK
      activity over extended periods using the compound 2-(2'-amino-3'-methoxyphenyl)
      oxanaphthalen-4-one (PD98059). Despite attaining up to 95% inhibition of p42/p44
      MAPK activity in cultures treated with NGF and PD98059, neuronal survival is
      maintained undiminished, although a decrease in the density of the neuritic
      network is observed. Because p21Ras activity is essential for NGF-induced
      survival, we conclude that p21Ras-linked activities other than p42 and p44 MAPKs
      are responsible for mediating NGF-dependent survival of rat sympathetic neurones.

PMID- 8863484
TI  - Differential compartmentalization of mRNAs in squid giant axon.
AB  - Previously, we reported that the squid giant axon contains a heterogeneous
      population of mRNAs that includes beta-actin, beta-tubulin, kinesin,
      neurofilament proteins, and enolase. To define the absolute levels and relative
      distribution of these mRNAs, we have used competitive reverse transcription-PCR
      to quantify the levels of five mRNAs present in the giant axon and giant fiber
      lobe (GFL), the location of the parental cell soma. In the GFL, the number of
      transcripts for these mRNAs varied over a fourfold range, with beta-tubulin being
      the most abundant mRNA species (1.25 x 10(9) molecules per GFL). Based on
      transcript number, the rank order of mRNA levels in the GFL was beta-tubulin >
      beta-actin > kinesin > enolase > microtubule-associated protein (MAP) H1. In
      contrast, kinesin mRNA was most abundant in the axon (4.1 x 10(7) molecules per
      axon) with individual mRNA levels varying 15-fold. The rank order of mRNA levels
      in the axon was kinesin > beta-tubulin > MAP H1 > beta-actin > enolase. The
      relative abundance of the mRNA species in the axon did not correlate with the
      size of the transcript, nor was it directly related to their corresponding levels
      in the GFL. Taken together, these findings confirm that significant amounts of
      mRNA are present in the giant axon and suggest that specific mRNAs are
      differentially transported into the axonal domain.

PMID- 8863485
TI  - Human astrocytoma cells (U-87 MG) exhibit a specific substance P binding site
      with the characteristics of an NK-1 receptor.
AB  - To investigate substance P (SP) receptors on an established human astrocytoma
      cell line (U-87 MG), [3H][Sar9,Met(O2)11]-SP, a selective SP receptor agonist,
      was used to identify and characterize the cell membrane binding sites for SP. SP
      receptor mRNA was examined by solution hybridization analysis, and the existence
      of SP binding protein on the surface of membranes was evaluated by flow cytometry
      using an anti-SP binding protein antibody. In U-87 MG and U-373 MG RNA
      preparations, transcripts were identified that corresponded to both mature and
      partially spliced receptor forms. In U-87 MG cell membrane-enriched preparations,
      the binding of [3H][Sar9,Met(O2)11]-SP was found to be time and cell number
      dependent, specific, saturable, and of high affinity. Equilibrium binding
      analysis revealed a single class of binding sites with an apparent KD of 1.15 +/-
      0.15 nM and a Bmax of 108 +/- 9.8 fmol/mg of protein. [3H][Sar9, Met(O2)11]-SP
      binding was basically not influenced by addition of mono (Na+, Li+) or divalent
      (Mg2+, Mn2+, Ca2+) cations; only high doses of divalent cations decreased the
      binding. GTP and guanylyl-5'-imidodiphosphate, but not GDP and GMP, reduced the
      Bmax without changing the affinity of [3H][Sar9,Met(O2)11]-SP. We also examined
      the effects of pretreatment with three lectins [concanavalin A (con A), wheat
      germ agglutinin (WGA), and Lens culinaris agglutinin (LCA)] to determine the
      nature of carbohydrate chains on the U-87 MG cell. Of three lectins analyzed for
      effects on agonist binding, WGA and LCA had an inhibitory effect, whereas con A
      was ineffective. These results suggest that SP receptors on the human astrocytoma
      cell line U-87 MG have either a biantennary complex-type or a high mannose-type
      of carbohydrate chain and may be regulated by GTP-binding protein(s).

PMID- 8863486
TI  - Induction of ganglioside biosynthesis and neurite outgrowth of primary cultured
      neurons by L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.
AB  - We reported previously that stereoisomers of 1-phenyl-2-decanoylamino-3
      morpholino-1-propanol (PDMP), the D-threo and L-threo forms, exerted inhibitory
      and stimulatory effects on glycosphingolipid (GSL) biosynthesis in B16 melanoma
      cells, respectively. In the present study, the primary cultured rat neocortical
      explants were treated with L- or D-threo-PDMP. These isomers exhibited opposite
      effects on neurite outgrowth: D-PDMP was inhibitory at concentrations ranging
      from 5 to 20 microM, whereas L-PDMP was stimulatory over the same concentration
      range, and the maximal effect was observed at 10-15 microM. Rat neocortical
      explants were doubly labeled with [14C]serine and [3H]galactose at 15 microM L-
      or D-PDMP. L-PDMP increased the incorporations of both labels into sphinganine,
      sphingosine, ceramide, sphingomyelin, neutral GSLs, and gangliosides, whereas D
      PDMP inhibited the glucosylation of ceramide resulting in a reduction of
      ganglioside biosynthesis and accumulation of precursors of glucosylceramide,
      ceramide, and sphingomyelin. To clarify the stimulatory effect of L-PDMP on GSL
      biosynthesis, serine palmitoyltransferase, sphingosine N-acyltransferase,
      glucosylceramide synthase, lactosylceramide synthase, GM3 synthase, and GD3
      synthase were quantified in cell lysates of explants pretreated with this agent.
      Serine palmitoyltransferase was fully activated up to 150% of the control.
      Furthermore, marked increases in the activities of lactosylceramide synthase
      (200%), GM3 synthase (240%), and GD3 synthase (300%) were observed. These results
      suggest that the neurotrophic action of L-PDMP may be ascribable to its
      stimulatory effect on the biosynthesis of GSLs, especially that of gangliosides.

PMID- 8863487
TI  - Modulation of major histocompatibility complex class I genes by interferon-gamma
      and ganglioside GT 1b in astrocytes: involvement of protein tyrosine
      phosphatases.
AB  - We have previously reported that the polysialoganglioside GT1b suppresses the
      induction of major histocompatibility complex class I molecules by interferon
      gamma in astrocytes. Suppression by GT1b depended on the presence of sialic acid
      moieties because asialo-GM1 was not suppressive. In the present report, GT1b was
      found to act transcriptionally to suppress class I genes because both the
      interferon-gamma induction of RNA and the activity of class I promoter constructs
      were inhibited. Furthermore, GT1b suppressed promoter activity through interferon
      regulatory factor elements, indicating an effect on the transcription activation
      factor, interferon regulatory factor 1. Interferon-gamma induced interferon
      regulatory factor 1 within 8 h, and GT1b suppressed this induction. The
      suppression of interferon regulatory factor 1 by GT1b correlated with the
      suppression of gamma-activated factor binding at the promoter of the interferon
      regulatory factor 1 gene. The suppression of gamma-activated factor by GT1b
      appeared to involve increased protein tyrosine phosphatase activity because
      treatment of the cells with pervanadate reversed the effect of GT1b on the gamma
      activated factor and, correspondingly, phosphotyrosine content. In sum, GT1b
      displays specific effects on interferon-gamma signaling and negative feedback
      regulatory molecules in astrocytes.

PMID- 8863488
TI  - Role of Na(+)-Ca2+ exchanger in agonist-induced Ca2+ signaling in cultured rat
      astrocytes.
AB  - We have previously demonstrated that activation of the Na(+)-Ca2+ exchanger in
      the reverse mode causes Ca2+ influx in astrocytes. In addition, we showed that
      the exchange activity was stimulated by nitric oxide (NO)/cyclic GMP and
      inhibited by ascorbic acid. The present study demonstrates that the Na(+)-Ca2+
      exchanger is involved in agonist-induced Ca2+ signaling in cultured rat
      astrocytes. The astrocytic intracellular Ca2+ concentration ([Ca2+]i) was
      increased by L-glutamate, noradrenaline (NA), and ATP, and the increases were all
      attenuated by the NO generator sodium nitroprusside (SNP). SNP also reduced the
      ionomycin-induced increase in [Ca2+]i. The NA-induced Ca2+ signal was also
      attenuated by S-nitroso-L-cysteine and 8-bromo cyclic GMP, whereas it was
      enhanced by 3,4-dichlorobenzamil, an inhibitor of the Na(+)-Ca2+ exchanger.
      Treatment of astrocytes with antisense, but not sense, deoxynucleotides to the
      sequence encoding the Na(+)-Ca2+ exchanger enhanced the ionomycin-induced
      increase in [Ca2+]i and blocked the effects of SNP and 8-bromo cyclic GMP in
      reducing the NA-induced Ca2+ signal. Furthermore, the ionomycin-induced Ca2+
      signal was enhanced by removal of extracellular Na+ and pretreatment with
      ascorbic acid. These findings indicate that the Na(+)-Ca2+ exchanger is a target
      for NO modulation of elevated [Ca2+]i and that the exchanger plays a role in Ca2+
      efflux when [Ca2+]i is raised above basal levels in astrocytes.

PMID- 8863489
TI  - Cytosolic proteolysis of tau by cathepsin D in hippocampus following suppression
      of cathepsins B and L.
AB  - Incubation of cultured hippocampal slices with an inhibitor [N-CBZ-L-phenylalanyl
      L-alanine-diazomethyl ketone (ZPAD)] of cathepsins B and L resulted in the
      degradation of high molecular weight isoforms of tau protein and the production
      of a 29-kDa tau fragment (tau 29). A tau antibody that is sensitive to the
      phosphorylated state of its epitopes did not recognize tau proteins or the tau 29
      fragment in slices that had been treated with a protein phosphatase inhibitor.
      This strongly suggests that the tau fragment was located in an extralysosomal
      compartment accessible to kinases and phosphatases. tau 29 exhibited a
      significant capacity for binding to microtubules and thus has the potential for
      interfering with normal tau-tubulin interactions. Three lines of evidence
      indicated that ZPAD-induced tau proteolysis was mediated by cathepsin D: (a)
      slices treated with the inhibitor had markedly elevated levels of cathepsin D in
      both lysosomal and extralysosomal compartments; (b) co-incubation of cathepsin D
      and tau at neutral pH resulted in a loss of intact tau proteins and production of
      a 28-kDa fragment; and (c) the lysosomotropic drug chloroquine blocked ZPAD
      induced increases in mature cathepsin D, and this was accompanied by a
      suppression of ZPAD-induced tau proteolysis. Changes in lysosomal hydrolases and
      cytoskeletal perturbations occur during brain aging. The present results suggest
      that the enzymatic and structural effects are related and, more specifically, are
      linked by alterations in the concentration and localization of cathepsin D. The
      tau fragments with microtubule binding capacity generated by cathepsin D could
      also be a source for the small polypeptides found in association with age-related
      pathological features.

PMID- 8863490
TI  - Two types of apoptotic cell death of rat central nervous system-derived
      neuroblastoma B50 and B104 cells: apoptosis induced during proliferation and
      after differentiation.
AB  - We describe here two types of apoptotic cell death observed in the rat CNS
      derived neuroblastoma B50 and B104 cells. One type was induced by dibutyryl
      cyclic AMP (DBcAMP) after differentiation, and the other was induced by treatment
      of proliferating cells with cycloheximide. When B50 and B104 cells were treated
      with 1 mM DBcAMP in the presence of 0.5% fetal calf serum, they began to extend
      neurites within 12 h and differentiated into neurons at 24 h, as reported
      previously. However, further cultivation with DBcAMP for up to 72 h led to
      flotation and, finally, death. Death was by apoptosis as shown by chromatin
      condensation and DNA fragmentation. Addition of a protein kinase A inhibitor or
      removal of DBcAMP after differentiation suppressed apoptosis, indicating the
      involvement of cyclic AMP and protein kinase A in apoptotic cell death. Cell
      death was also induced in proliferating cells without neurite outgrowth by
      treatment with cycloheximide. The death was also judged to be by apoptosis based
      on chromatin condensation and apoptotic body formation, although DNA
      fragmentation into small sizes was not detected. Both types of cell death showed
      similar responses to inhibitors for protein kinases and protein phosphatases.

PMID- 8863491
TI  - Changes of free long-chain bases in neuronal cells during differentiation and
      aging in culture.
AB  - Changes in the free long-chain base (LCB) composition in rat cerebellar granule
      cells in culture were studied during differentiation and aging. The total LCB
      mixtures, extracted from the cells maintained in culture up to 22 days, were
      derivatized with o-phthalaldehyde and fractionated by reversed-phase HPLC, and
      each LCB species was quantified. Four main LCBs were components of the total LCB
      mixtures of cultured cells: C18-sphingosine, C18-sphinganine, C20-sphingosine,
      and C20-sphinganine. They were found in all the cells analyzed, from 0 to 22 days
      of culture, with their contents being in the sequence C18-sphingosine > C18
      sphinganine > C20-sphingosine > C20-sphinganine and varying from 0.02 +/- 0.015
      pmol/mg of cell protein for C20-sphinganine at day 0 to 223 +/- 22 pmol/mg of
      cell protein for C18-sphingosine at day 8. Sphinganines were found to be minor
      components of the total LCB mixture, with C20-sphinganine being particularly
      scarce in nondifferentiated cells. The cell content of C20-sphinganine
      progressively increased from day 0 to 22 of culture; that of C18-sphinganine
      increased up to day 8, when cells are differentiated, and then remained quite
      constant. The changes of C18- and C20-sphingosine levels during cell culture were
      qualitatively similar to those of C18- and C20-sphinganine, but the content of
      the sphingosines was much higher than that of the sphinganines.

PMID- 8863492
TI  - Tissue-specific expression of the vasoactive intestinal peptide gene requires
      both an upstream tissue specifier element and the 5' proximal cyclic AMP
      responsive element.
AB  - An upstream enhancer element [tissue specifier element (TSE)] located between
      4.66 and 4.02 kb from the transcription start site is important for cell type
      specific expression and phorbol ester induction of the vasoactive intestinal
      peptide (VIP) gene. An element located within 100 bases of the VIP promoter [the
      VIP cyclic AMP-responsive element (VIP-CRE)] confers cyclic AMP and phorbol ester
      responsiveness to heterologous promoters. The possibility that these two regions
      of the VIP gene function cooperatively to determine tissue-specific and second
      messenger-dependent expression of the VIP gene was addressed by assaying
      transcription from a VIP-luciferase reporter gene with progressive deletions from
      the 5' flanking sequence of the gene, with or without inactivation of the
      proximal VIP-CRE. Basal expression of the reporter gene in both SH-EP and SK-N-SH
      human neuroblastoma cells, which express endogenous VIP mRNA, was absolutely
      dependent on the presence of the upstream TSE. Full constitutive expression was
      also dependent on the intact VIP-CRE. Forskolin-mediated induction of the
      reporter gene in SH-EP and SK-N-SH cells was completely abolished by mutations in
      the VIP-CRE but not by deletion of the upstream sequence, indicating that the VIP
      CRE alone determines cyclic AMP responsiveness. In contrast to reports that the
      VIP-CRE imparts 12-O-tetradecanoylphorbol 13-acetate (phorbol 12-myristate 13
      acetate; PMA) responsiveness to heterologous promoters, PMA stimulation in SK-N
      SH cells was independent of an intact VIP-CRE but dependent on a region between 
      2.5 kb and the VIP-CRE. Sequencing of the entire 5.2-kb VIP 5' flank revealed a
      consensus PMA-responsive element (TGACTCA) 2.25 kb upstream of the transcription
      start site that may represent the site imparting PMA responsiveness to the VIP
      gene.

PMID- 8863493
TI  - Increased activity-regulating and neuroprotective efficacy of alpha-secretase
      derived secreted amyloid precursor protein conferred by a C-terminal heparin
      binding domain.
AB  - Proteolytic cleavage of beta-amyloid precursor protein (beta APP) by alpha
      secretase results in release of one secreted form (sAPP) of APP (sAPP alpha),
      whereas cleavage by beta-secretase releases a C-terminally truncated sAPP (sAPP
      beta) plus amyloid beta-peptide (A beta). beta APP mutations linked to some
      inherited forms of Alzheimer's disease may alter its processing such that levels
      of sAPP alpha are reduced and levels of sAPP beta increased. sAPP alpha s may
      play important roles in neuronal plasticity and survival, whereas A beta can be
      neurotoxic. sAPP alpha was approximately 100-fold more potent than sAPP beta in
      protecting hippocampal neurons against excitotoxicity, A beta toxicity, and
      glucose deprivation. Whole-cell patch clamp and calcium imaging analyses showed
      that sAPP beta was less effective than sAPP alpha in suppressing synaptic
      activity, activating K+ channels, and attenuating calcium responses to glutamate.
      Using various truncated sAPP alpha and sAPP beta APP695 products generated by
      eukaryotic and prokaryotic expression systems, and synthetic sAPP peptides, the
      activity of sAPP alpha was localized to amino acids 591-612 at the C-terminus.
      Heparinases greatly reduced the actions of sAPP alpha s, indicating a role for a
      heparin-binding domain at the C-terminus of sAPP alpha in receptor activation.
      These findings indicate that alternative processing of beta APP has profound
      effects on the bioactivity of the resultant sAPP products and suggest that
      reduced levels of sAPP alpha could contribute to neuronal degeneration in
      Alzheimer's disease.

PMID- 8863494
TI  - Creation and characterization of mitochondrial DNA-depleted cell lines with
      "neuronal-like" properties.
AB  - Mitochondrial dysfunction and attendant bioenergetic defects are increasingly
      recognized as playing an important role in neurodegenerative disorders. The
      increased attention on mitochondrial involvement points to the need for
      developing cell lines that have neuron-like characteristics for the genetic
      analysis and modeling of these diseases. We describe the creation of respiratory
      deficient SH-SY5Y neuroblastoma cell lines (rho zero 64/5) by selectively
      depleting mitochondrial DNA through prolonged exposure to ethidium bromide.
      Oxygen consumption in these cells and activities of the electron transport chain
      enzyme complexes I and IV that contain subunits encoded by the mitochondrial
      genome are eliminated. In contrast, the function of complex II, a nuclear-encoded
      electron transport chain component, is largely intact in these cells. The rho
      zero 64/5 cells retain the ability to differentiate into cells with neuron-like
      phenotypes following treatment with phorbol ester or retinoic acid. Normal
      respiratory function is recovered by repopulation of rho zero 64/5 cells with
      exogenous human platelet mitochondria. The rho zero 64/5 cell line serves as a
      valuable model for the study of neurologic diseases suspected of involving
      mitochondrial dysfunction.

PMID- 8863495
TI  - Apoptosis induced by differentiation or serum deprivation in an immortalized
      central nervous system neuronal cell line.
AB  - To characterize the nature of programmed cell death (PCD) induced in neuronal
      cells during development, three regulators of apoptosis were investigated: one,
      the bcl-2-related genes, modulate cell survival, and the other two, the
      interleukin-1 beta converting enzyme (ICE)-related enzymes and the tumor
      suppressor protein p53, have been implicated as mediators of apoptosis. These
      regulators were studied in H19-7 cells, an SV40 Tts-immortalized rat hippocampal
      neuronal cell line that can be differentiated with basic fibroblast growth factor
      at the nonpermissive temperature, resulting in a rapid attrition of cells by
      apoptosis. PCD occurred by two mechanisms in H19-7 cells: The first was initiated
      by removal of serum from undifferentiated cells, and the second was a consequence
      of neuronal differentiation. In differentiated H19-7 cells, the survival time was
      increased by both human bcl-2 and bcl-xL, and this could be reversed by bcl-xs.
      Addition of a peptide inhibitor of the ICE enzyme family to H19-7 cells resulted
      in a transient protection against differentiation-associated apoptosis, whereas
      no further protection was observed in the BCL-2- or BCL-XL-expressing cells.
      Shifting the differentiated cells to 33 degrees C to inactivate p53 did not
      significantly affect the apoptotic process, indicating that apoptosis induced by
      neuronal differentiation is not dependent on the continued presence of p53. By
      contrast, in undifferentiated cells, cell loss induced by transfer to serum-free
      media occurred more rapidly on inactivation of large T, consistent with p53
      involvement. This medium-induced decrease in cell survival could not be rescued
      by the ICE inhibitor but was partially rescued by BCL-2 or BCL-XL. Furthermore,
      studies involving expression of BCL-2 and BCL-XL alone or together revealed
      differences in the survival dependent on the cellular environment. These results
      suggest that apoptosis of neuronal cells occurs by at least two processes: one in
      undifferentiated cells initiated by removal of serum and one linked to
      differentiation. The data implicate the ICE enzyme family but not p53 in
      apoptosis induced by differentiation and demonstrate that either BCL-2 or BCL-XL
      can prolong the survival of differentiated neuronal cells.

PMID- 8863496
TI  - Chronic exposure to adenosine receptor agonists and antagonists reciprocally
      regulates the A1 adenosine receptor-adenylyl cyclase system in cerebellar granule
      cells.
AB  - Chronic treatment with the adenosine receptor antagonist caffeine evokes an up
      regulation of A1 adenosine receptors and increased coupling of the receptor to G
      proteins in rat brain membranes. However, chronic agonist exposure has not been
      explored. Primary cultures of cerebellar granule cells were exposed chronically
      to A1 adenosine receptor agonists and antagonists. Exposure to the A1 adenosine
      receptor agonist N6-cyclopentyladenosine resulted in (1) a time- and
      concentration-dependent reduction in the density of receptors labeled by 1,3
      [3H]dipropyl-8-cyclopentylxanthine, (2) an enhanced ability of guanyl nucleotides
      to decrease the fraction of A1 adenosine receptor sites displaying high affinity
      for 2-chloroadenosine, and (3) a functional uncoupling of receptors from adenylyl
      cyclase (EC 4.6.1.1). The adenosine antagonists caffeine and 8-p
      sulfophenyltheophylline produced alterations in A1 adenosine receptor homeostasis
      that were antipodal to those associated with agonist treatment. Antagonist
      exposure (1) increased the density of A1 adenosine receptors in cerebellar
      granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor
      coupling to G proteins, and (3) increased the functional coupling of receptors to
      adenylyl cyclase inhibition. Forskolin treatment of cerebellar granule cells did
      not affect receptor density, suggesting that cyclic AMP is not involved in the
      regulation of A1 adenosine receptor expression.

PMID- 8863497
TI  - Effects of (-)-sulpiride on dopamine release in striatum of developing rats:
      degree of depolarization influences responsiveness.
AB  - The purpose of this study was to determine the effects of localized delivery of
      the D2 antagonist (-)-sulpiride (via microdialysis) on spontaneous and evoked
      dopamine release in the neostriatum of urethane-anesthetized rats 5, 10, 15, 21,
      and 70 days of age. Sulpiride increased spontaneous dopamine release
      approximately threefold relative to baseline measures, and this effect decreased
      with maturation. The relationship between sulpiride- and potassium-evoked release
      was complex; sulpiride increased evoked dopamine outflow at 5, 10, and 15 days of
      age. At 21 and 70 days of age, however, the effects of sulpiride were inversely
      related to the degree of stimulation with potassium. Furthermore, the D2 agonist
      quinpirole (100 microM) reversed the effects of sulpiride (10 microM), suggesting
      receptor mediation. These experiments demonstrate that the maturational decline
      in the efficacy and potency of D2 antagonism appears to be related to the degree
      of stimulation at the nerve terminal.

PMID- 8863498
TI  - Lack of a precursor-product relationship between histamine and its metabolites in
      brain after histidine loading.
AB  - Levels of histamine and its major metabolites in brain, tele-methylhistamine (t
      MH) and tele-methylimidazoleacetic acid (t-MIAA), were measured in rat brains up
      to 12 h after intraperitoneal administration of L-histidine (His), the precursor
      of histamine. Compared with saline-treated controls, mean levels of histamine
      were elevated at 1 h (+102%) after a 500 mg/kg dose; levels of t-MH did not
      increase. Following a 1,000 mg/kg dose, mean histamine levels were increased for
      up to 7 h, peaked at 3 h, and returned to control levels within 12 h. In
      contrast, levels of t-MH showed a small increase only after 3 h; levels of t-MIAA
      remained unchanged after either dose. Failure of most newly formed histamine to
      undergo methylation, its major route of metabolism in brain, suggested that
      histamine was metabolized by another mechanism possibly following nonspecific
      decarboxylation. To test this hypothesis, other rats were injected with alpha
      fluoromethylhistidine (alpha-FMHis; 75 mg/kg, i.p.), an irreversible inhibitor of
      specific histidine decarboxylase. Six hours after rats received alpha-FMHis, the
      mean brain histamine level was reduced 30% compared with saline-treated controls.
      Rats given His (1,000 mg/kg) 3 h after alpha-FMHis (75 mg/kg) and examined 3 h
      later had a higher (+112%) mean level of histamine than rats given alpha-FMHis,
      followed by saline. Levels of t-MH and t-MIAA did not increase. These results
      imply that high doses of His distort the simple precursor-product relationship
      between histamine and its methylated metabolites in brain. The possibility that
      some His may undergo nonspecific decarboxylation in brain after His loading is
      discussed. These findings, and other actions of His independent of histamine,
      raise questions about the validity of using His loading as a specific probe of
      brain histaminergic function.

PMID- 8863499
TI  - Differential effects of ipsapirone on 5-hydroxytryptamine release in the dorsal
      and median raphe neuronal pathways.
AB  - Serotonergic neurons of the dorsal and median raphe nuclei are morphologically
      dissimilar. Recent results challenge previous evidence indicating a greater
      inhibition of dorsal raphe neurons after 5-hydroxytryptamine1A (5-HT1A)
      autoreceptor activation. As both nuclei innervate different forebrain
      territories, this issue is critical to understanding the changes in brain
      function induced by anxiolytic and antidepressant drugs. Using microdialysis, we
      examined the modifications of 5-HT release induced by the selective 5-HT1A
      agonist ipsapirone in both neuronal pathways. Maximal and minimal basal 5-HT
      values (in the presence of 1 microM citalopram) were 45.0 +/- 4.8 fmol/fraction
      in the median raphe nucleus and 8.4 +/- 0.4 fmol/fraction in the dorsal
      hippocampus. Ipsapirone (0.3, 3, and 10 mg/kg s.c.) reduced dose-dependently 5-HT
      in the two raphe nuclei and four forebrain areas. Maximal reductions (to
      approximately 25% of predrug values) were observed in cortex and striatum and in
      median raphe nucleus. The effects were more moderate in dorsal and ventral
      hippocampus (to 66 and 50% of baseline, respectively). These results are
      consistent with a higher sensitivity of dorsal raphe neurons to 5-HT1A
      autoreceptor activation. Yet the differential reduction of 5-HT release in the
      median raphe nucleus and hippocampus suggests the presence of complex mechanisms
      of control of 5-HT release in these neurons.

PMID- 8863500
TI  - Multiple determinants of dihydro-beta-erythroidine sensitivity on rat neuronal
      nicotinic receptor alpha subunits.
AB  - Neuronal nicotinic acetylcholine receptors are differentially sensitive to
      blockade by the competitive antagonist dihydro-beta-erythroidine. Both alpha and
      beta subunits participate in determining sensitivity to this antagonist. The
      alpha subunit contribution to dihydro-beta-erythroidine sensitivity is
      illustrated by comparing the alpha 4 beta 4 receptor and the alpha 3 beta 4
      receptor, which differ in sensitivity to dihydro-beta-erythroidine by
      approximately 120-fold. IC50 values for blocking alpha 4 beta 4 and alpha 3 beta
      4, responding to EC20 concentrations of acetylcholine, were 0.19 +/- 0.06 and
      23.1 +/- 10.2 microM, respectively. To map the sequence segments responsible for
      this difference, we constructed a series of chimeric alpha subunits containing
      portions of the alpha 4 and alpha 3 subunits. These chimeras were coexpressed
      with beta 4, allowing pharmacological characterization. We found determinants of
      dihydro-beta-erythroidine sensitivity to be distributed throughout the N-terminal
      extracellular domain of the alpha subunit. These determinants were localized to
      sequence segments 1-94, 94-152, and 195-215. Loss of determinants within segment
      1-94 had the largest effect, decreasing dihydro-beta-erythroidine sensitivity by
      4.3-fold.

PMID- 8863501
TI  - Differential inhibition of secretagogue-stimulated sodium uptake in adrenal
      chromaffin cells by activation of D4 and D5 dopamine receptors.
AB  - Recent studies have demonstrated that D1-selective and D2-selective dopamine
      receptor agonists inhibit catecholamine secretion and Ca2+ uptake into bovine
      adrenal chromaffin cells by receptor subtypes that we have identified by PCR as
      D5, a member of the D1-like dopamine receptor subfamily, and D4, a member of the
      D2-like dopamine receptor subfamily. The purpose of this study was to determine
      whether activation of D5 or D4 receptors inhibits influx of Na+, which could
      explain inhibition of secretion and Ca2+ uptake by dopamine agonists. D1
      selective agonists preferentially inhibited both dimethylphenylpiperazinium-
      (DMPP) and veratridine-stimulated 22Na+ influx into chromaffin cells. The D1
      selective agonists chloro-APB hydrobromide (CI-APB; 100 microM) and SKF-38393 (<
      00 microM) inhibited DMPP-stimulated Na+ uptake by 87.5 +/- 2.3 and 59.7 +/-
      4.5%, respectively, whereas the D2-selective agonist bromocriptine (100 microM)
      inhibited Na+ uptake by only 22.9 +/- 5.0%. Veratridine-stimulated Na+ uptake was
      inhibited 95.1 +/- 3.2 and 25.7 +/- 4.7% by 100 microM CI-APB or bromocriptine,
      respectively. The effect of CI-APB was concentration dependent. A similar IC50
      (approximately 18 microM) for inhibition of both DMPP- and veratridine-stimulated
      Na+ uptake was obtained. The addition of 8-bromo-cyclic AMP (1 mM) had no effect
      on either DMPP- or veratridine-stimulated Na+ uptake. These observations suggest
      that D1-selective agonists are inhibiting secretagogue-stimulated Na+ uptake in a
      cyclic AMP-independent manner.

PMID- 8863502
TI  - Effects of subchronic clozapine and haloperidol on striatal glutamatergic
      synapses.
AB  - Subchronic treatment with haloperidol increases the number of asymmetric
      glutamate synapses associated with a perforated postsynaptic density in the
      striatum. To characterize these synaptic changes further, the effects of
      subchronic (28 days) administration of an atypical antipsychotic, clozapine (30
      mg/kg, s.c.), or a typical antipsychotic, haloperidol (0.5 mg/kg, s.c.), on the
      binding of [3H] MK-801 to the NMDA receptor-linked ion channel complex and on the
      in situ hybridization of riboprobes for NMDAR2A and 2B subunits and splice
      variants of the NMDAR1 subunit were examined in striatal preparations from rats.
      The density of striatal glutamate immunogold labeling associated with nerve
      terminals of all asymmetric synapses and the immunoreactivity of those asymmetric
      synapses associated with a perforated postsynaptic density were also examined by
      electron microscopy. Subchronic neuroleptic administration had no effect on [3H]
      MK-801 binding to striatal membrane preparations. Both drugs increased glutamate
      immunogold labeling in nerve terminals of all asymmetric synapses, but only
      haloperidol increased the density of glutamate immunoreactivity within nerve
      terminals of asymmetric synapses containing a perforated postsynaptic density.
      Whereas subchronic administration of clozapine, but not haloperidol, resulted in
      a significant increase in the hybridization of a riboprobe that labels all splice
      variants of the NMDAR1 subunit, both drugs significantly decreased the abundance
      of NMDAR1 subunit mRNA containing a 63-base insert. Neither drug altered mRNA for
      the 2A subunit, but clozapine significantly increased hybridization of a probe
      for the 2B subunit. The data suggest that some neuroleptic effects may be
      mediated by glutamatergic systems and that typical and atypical antipsychotics
      can have varying effects on the density of glutamate in presynaptic terminals and
      on the expression of specific NMDA receptor splice variant mRNAs. Alternatively,
      NMDAR1 subunit splice variants may differentially respond to interactions with
      glutamate.

PMID- 8863503
TI  - Nicotinic autoreceptors mediating enhancement of acetylcholine release become
      operative in conditions of "impaired" cholinergic presynaptic function.
AB  - The existence in the mammalian CNS of release-inhibiting muscarinic autoreceptors
      is well established. In contrast, few reports have focused on nicotinic
      autoreceptors mediating enhancement of acetylcholine (ACh) release. Moreover, it
      is unclear under what conditions the function of one type of autoreceptor
      prevails over that of the other. Rat cerebrocortex slices, prelabeled with
      [3H]choline, were stimulated electrically at 3 or 0.1 Hz. The release of [3H]ACh
      evoked at both frequencies was inhibited by oxotremorine, a muscarinic receptor
      agonist, and stimulated by atropine, a muscarinic antagonist. Nicotine,
      ineffective at 3 Hz, enhanced [3H]ACh release at 0.1 Hz; mecamylamine, a
      nicotinic antagonist, had no effect at 3 Hz but inhibited [3H]ACh release at 0.1
      Hz. The cholinesterase inhibitor neostigmine decreased [3H]ACh release at 3 Hz
      but not at 0.1 Hz; in the presence of atropine, neostigmine potentiated [3H]ACh
      release, an effect blocked by mecamylamine. In synaptosomes depolarized with 15
      mM KCl, ACh inhibited [3H]ACh release; this inhibition was reversed to an
      enhancement when the external [Ca2+] was lowered. The same occurred when, at 1.2
      mM Ca2+, external [K+] was decreased. Oxotremorine still inhibited [3H]ACh
      release at 0.1 mM Ca2+. When muscarinic receptors were inactivated with atropine,
      the K+ (15 mM)-evoked release of [3H]ACh (at 0.1 mM Ca2+) was potently enhanced
      by ACh acting at nicotinic receptors (EC50 approximately 0.6 microM). In
      conclusion, synaptic ACh concentration does not seem to determine whether
      muscarinic or nicotinic autoreceptors are activated. Although muscarinic
      autoreceptors prevail under normal conditions, nicotinic autoreceptors appear to
      become responsive to endogenous ACh and to exogenous nicotinic agents under
      conditions mimicking impairment of ACh release. Our data may explain in part the
      reported efficacy of cholinesterase inhibitors (and nicotinic agonists) in
      Alzheimer's disease.

PMID- 8863504
TI  - Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter
      GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of
      GLP-1 receptor agonists as an inhibitory signal for food and water intake.
AB  - This study was designed to determine the possible role of brain glucagon-like
      peptide-1 (GLP-1) receptors in feeding behavior. In situ hybridization showed
      colocalization of the mRNAs for GLP-1 receptors, glucokinase, and GLUT-2 in the
      third ventricle wall and adjacent arcuate nucleus, median eminence, and
      supraoptic nucleus. These brain areas are considered to contain glucose-sensitive
      neurons mediating feeding behavior. Because GLP-1 receptors, GLUT-2, and
      glucokinase are proteins involved in the multistep process of glucose sensing in
      pancreatic beta cells, the colocalization of specific GLP-1 receptors and glucose
      sensing-related proteins in hypothalamic neurons supports a role of this peptide
      in the hypothalamic regulation of macronutrient and water intake. This hypothesis
      was confirmed by analyzing the effects of both systemic and central
      administration of GLP-1 receptor ligands. Acute or subchronic intraperitoneal
      administration of GLP-1 (7-36) amide did not modify food and water intake,
      although a dose-dependent loss of body weight gain was observed 24 h after acute
      administration of the higher dose of the peptide. By contrast, the
      intracerebroventricular (i.c.v.) administration of GLP-1 (7-36) amide produced a
      biphasic effect on food intake characterized by an increase in the amount of food
      intake after acute i.c.v. delivery of 100 ng of the peptide. There was a marked
      reduction of food ingestion with the 1,000 and 2,000 ng doses of the peptide,
      which also produced a significant decrease of water intake. These effects seemed
      to be specific because i.c.v. administration of GLP-1 (1-37), a peptide with
      lower biological activity than GLP-1 (7-36) amide, did not change feeding
      behavior in food-deprived animals. Exendin-4, when given by i.c.v. administration
      in a broad range of doses (0.2, 1, 5, 25, 100, and 500 ng), proved to be a potent
      agonist of GLP-1 (7-36) amide. It decreased, in a dose-dependent manner, both
      food and water intake, starting at the dose of 25 ng per injection. Pretreatment
      with an i.c.v. dose of a GLP-1 receptor antagonist [exendin (9-39); 2,500 ng]
      reversed the inhibitory effects of GLP-1 (7-36) amide (1,000 ng dose) and exendin
      4 (25 ng dose) on food and water ingestion. These findings suggest that GLP-1 (7
      36) amide may modulate both food and drink intake in the rat through a central
      mechanism.

PMID- 8863505
TI  - Brain polyamine stress response: recurrence after repetitive stressor and
      inhibition by lithium.
AB  - We recently demonstrated that, unlike in peripheral tissues, the increase in
      activity of polyamine synthesizing enzymes observed in the brain after acute
      stress can be prevented by long-term, but not by short-term, treatment with
      lithium. In the present study we sought to examine the effects of chronic
      intermittent stress on two key polyamine synthesizing enzymes, ornithine
      decarboxylase and S-adenosylmethionine decarboxylase, and their modulation by
      lithium treatment. Adult male rats were subjected to 2 h of restraint stress once
      daily for 5 days and to an additional delayed stress episode 7 days later. Enzyme
      activities were assayed 6 h after the beginning of each stress episode. In
      contrast to the liver, where ornithine decarboxylase activity was increased (300%
      of the control) only after the first stress episode, the enzyme activity in the
      brain was increased after each stress episode (to approximately 170% of the
      control). Unlike ornithine decarboxylase activity, S-adenosylmethionine
      decarboxylase activity was slightly reduced after the first episode (86% of the
      control) but remained unchanged thereafter. After cessation of the intermittent
      stress period, an additional stress episode 7 days later led again to an increase
      in ornithine decarboxylase activity in the brain (225% of the control) but not in
      the liver, whereas S-adenosylmethionine decarboxylase activity remained
      unchanged. The later increase in ornithine decarboxylase activity was blocked by
      lithium treatment during the intervening 7-day interval between stressors. The
      results warrant the following conclusions: (a) Repetitive application of
      stressors results in a recurrent increase in ornithine decarboxylase activity in
      the brain but to habituation of this response in the liver. (b) This brain
      polyamine stress response can be blocked by long-term (days) lithium treatment.
      (c) The study implicates an overreactive polyamine response as a component of the
      adaptive, or maladaptive, brain response to stressful events and as a novel
      molecular target for lithium action.

PMID- 8863506
TI  - Aggregation of neurofilaments in NF-L transfected neuronal cells: regeneration of
      the filamentous network by a protein kinase C inhibitor.
AB  - Cytoplasmic inclusion bodies that are accumulations of neurofilaments are the
      pathological hallmark of many neurodegenerative diseases and have been produced
      in transgenic mice by overexpression of mouse (NF-L and NF-M; light and medium
      chains, respectively) and human (NF-M and NF-H; medium and heavy chains,
      respectively) neurofilament subunits. This report describes a neuronal culture
      model in which human NF-L was overexpressed to produce cytoplasmic accumulations
      of neurofilaments within cell bodies concomitant with the collapse of the
      endogenous neurofilament network. Electron microscopy showed that, within
      accumulations, neurofilaments retained a filamentous structure. The culture model
      thus provides a novel system in which the effect on neurofilament accumulations
      of manipulating protein phosphorylation can be studied. Treatment of cells
      containing neurofilament accumulations with bisindolylmaleimide, a specific
      protein kinase C inhibitor, resulted in regeneration of the filamentous network;
      this effect was not due to a change in the level of transfected NF-L expression.
      These findings lend support to the suggestion that an impairment in the
      regulation of protein phosphorylation may lead to the accumulation of
      neurofilaments seen in neurodegenerative disease.

PMID- 8863507
TI  - Global brain ischemia and reperfusion: modifications in eukaryotic initiation
      factors associated with inhibition of translation initiation.
AB  - We used in vitro translation and antibodies against phosphoserine and the
      eukaryotic initiation factors elF-4E, elF-4G, and elF-2 alpha to examine the
      effects of global brain ischemia and reperfusion on translation initiation and
      its regulation in a rat model of 10 min of cardiac arrest followed by
      resuscitation and 90 min of reperfusion. Translation reactions were performed on
      postmitochondrial supernatants from brain homogenates with and without
      aurintricarboxylic acid to separate incorporation due to run-off from
      incorporation due to peptide synthesis initiated in vitro. The rate of leucine
      incorporation due to in vitro-initiated protein synthesis in normal forebrain
      homogenates was approximately 0.4 fmol of leucine/min/microgram of protein and
      was unaffected by 10 min of cardiac arrest, but 90 min of reperfusion reduced
      this rate 83%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      western blots of these homogenates showed that neither 10 min of global brain
      ischemia nor 90 min of reperfusion induced significant alterations in the
      quantity or serine phosphorylation of elF-4E. However, we observed in all 90-min
      reperfused samples elF-4G fragments that also bound elF-4E. The amount of elF-2
      alpha was not altered by ischemia or reperfusion, and immunoblotting after
      isoelectric focusing did not detect serine-phosphorylated elF-2 alpha in normal
      samples or in those obtained after ischemia without reperfusion. However, serine
      phosphorylated elF-2 alpha was uniformly present after 90 min of reperfusion and
      represented 24 +/- 3% of the elF-2 alpha in these samples. The serine
      phosphorylation of elF-2 alpha and partial fragmentation of elF-4G observed after
      90 min of reperfusion offer an explanation for the inhibition of protein
      synthesis.

PMID- 8863508
TI  - Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases
      have increased levels of neurofilament protein in CSF.
AB  - In the present study we describe an ELISA to quantify the light subunit of the
      neurofilament triplet protein (NFL) in CSF. The method was validated by measuring
      CSF NFL concentrations in healthy individuals and in two well-characterized
      groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's
      disease (AD). The levels were increased in ALS (1,743 +/- 1,661 ng/L; mean +/-
      SD) and AD (346 +/- 176 ng/L) compared with controls (138 +/- 31 ng/L; p < 0.0001
      for both). Within the ALS group, patients with lower motor neuron signs only had
      lower NFL levels (360 +/- 237 ng/L) than those with signs of upper motor neuron
      disease (2,435 +/- 1,633 ng/L) (p < 0.05). In a second study patients with
      miscellaneous neurodegenerative diseases were investigated (vascular dementia,
      olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral
      infarctions, and multiple sclerosis), and the CSF NFL level was found to be
      increased (665 +/- 385 ng/L; p < 0.0001). NFL is a main structural protein of
      axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in
      general, but particularly in ALS with involvement of the pyramidal tract.

PMID- 8863509
TI  - Changes in brain protease activity in aging.
AB  - We measured changes in protease activity with aging, conducting assays of
      cathepsin D and calpain II activities and the rate of degradation of cytoskeletal
      proteins, preparing the enzymes and substrates from young and aged brains.
      Calpain preparations added to the young and to the aged substrates were
      standardized with casein as substrate so that age-related changes in calpain
      specificity and substrate susceptibility were measured. Several age-related
      differences were observed in substrate susceptibility and in enzyme activity.
      With respect to substrate, the neurofilament protein from young animals was
      somewhat more susceptible to calpain action than that from older animals. With
      respect to enzyme activity, calpain from aged brain cleaved neurofilament protein
      at a faster rate than did calpain from young. With neurofilaments, the most rapid
      breakdown usually occurred when enzyme from aged tissue was incubated with
      substrate from young. Kidney enzyme of aged rats incubated with neurofilament
      substrate of aged rats resulted in a more rapid breakdown than enzyme of young
      kidney incubated with substrate of young. The age dependence of tubulin breakdown
      was somewhat different from that of neurofilament breakdown. The most rapid
      breakdown usually occurred when using enzyme from young with tubulin from young.
      Incubation of neurofilament protein or tubulin with cathepsin D did not reveal
      any differences with aging. These studies suggest that an increase in enzyme
      activity observed previously during aging may also include changes in the
      properties of the enzyme (substrate specificity) and/or in the properties of
      their endogenous substrates (susceptibility to breakdown).

PMID- 8863510
TI  - Metabolite changes in the cerebral cortex of treated and untreated infant
      hydrocephalic rats studied using in vitro 31P-NMR spectroscopy.
AB  - The effect of hydrocephalus on cerebral energy metabolites and on intermediates
      of membrane phospholipid metabolism has been studied in H-Tx rats with inherited
      infantile hydrocephalus. Hydrocephalic rats and rats with shunts placed at 4-5
      days or at 10 days after birth were subjected to magnetic resonance imaging in
      vivo before 21 days of age to determine the dimensions of the ventricles and
      cortex. At 21 days, the brains from the three groups of rats, together with age
      matched control littermates, were frozen in situ, and chloroform/methanol
      extracts of cerebral cortex were prepared for high-resolution 31P-NMR
      spectroscopy. Hydrocephalus resulted in modest decreases in most metabolites
      quantified. Levels of phosphocreatine, ATP, and diphosphodiesters plus NAD were
      significantly reduced by 23-32%, and inorganic phosphate content was reduced but
      not significantly. Levels of the membrane phospholipid intermediates
      phosphorylethanolamine, glycerophosphorylethanolamine, and
      glycerophosphorylcholine were also significantly reduced by 30-33%, indicating
      changes in membrane metabolism. These general decreases are consistent with a
      loss of cell contents, possibly due to changes in dendrite structure in
      hydrocephalus. Rats shunt-treated at 4-5 days were similar to control rats for
      all energy metabolites, but those treated later at 10 days had reduced
      phosphocreatine and ATP levels. Shunt-treated rats also had reductions in levels
      of membrane phospholipids, some of which occurred in sham-operated rats. It is
      concluded that hydrocephalus leads to reductions in levels of energy metabolites
      and in levels of membrane phospholipids and that the changes in energy
      metabolites can be reversed by early, but not by later, shunt treatment.

PMID- 8863511
TI  - Interleukin-1 beta and tumor necrosis factor-alpha induce expression of alpha 1
      antichymotrypsin in human astrocytoma cells by activation of nuclear factor-kappa
      B.
AB  - The protease inhibitor alpha 1-antichymotrypsin (ACT) has been suggested to be
      involved in the etiology of Alzheimer's disease (AD). Increased levels of ACT
      have been found in serum and brains of AD patients, and ACT has been proposed to
      regulate beta-amyloid fibril formation in vitro. To gain insight into the
      regulation of ACT in the brain, we investigated the signal transduction pathways
      involved in ACT gene expression and protein synthesis in the human astrocytoma
      cell line U373. This cell line has previously been shown to respond with strong
      ACT synthesis on stimulation with interleukin-1 beta (IL-1 beta) or tumor
      necrosis factor-alpha (TNF alpha). Here, we describe that both IL-1 beta and TNF
      alpha activate the transcription factor nuclear factor-kappa B (NF-kappa B) via
      production of reactive oxygen intermediates resulting in ACT expression. In
      addition, we show that neither protein kinase C nor protein kinase A is involved
      in IL-1 beta- or TNF alpha-induced ACT expression. These results suggest that
      activation of NF-kappa B may be one possible cause of increased ACT levels in AD
      and provide a basis for the development of drugs used for the modulation of
      inflammatory processes occurring in AD.

PMID- 8863512
TI  - Prevention of hyperoxia-induced alterations in synaptosomal membrane-associated
      proteins by N-tert-butyl-alpha-phenylnitrone and 4-hydroxy-2,2,6,6
      tetramethylpiperidin-1-oxyl (Tempol).
AB  - Hyperoxia has been considered a model of free radical reactive oxygen species
      production in aging and age-related disorders. Previously, we studied the
      membrane protein alterations that occur during hyperoxia; we found that exposure
      of young animals to 24 h of hyperoxia provided the greatest degree of oxidation
      of cortical synaptosomal membrane proteins. We reasoned that free radical
      oxidation was involved in this protein oxidation. In accordance, in the current
      study we investigated the protective nature of two known free radical scavengers,
      N-tert-butyl-alpha-phenylnitrone (PBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidin
      1-oxyl (Tempol), against 24-h hyperoxia damage. The three techniques used in this
      study were electron paramagnetic resonance (EPR) protein-specific spin labeling,
      assay of the activity of the oxidatively sensitive enzyme glutamine synthetase
      (GS), and measurement of protein carbonyl content. Before hyperoxia, gerbils
      received intraperitoneal injections of varying concentrations of either of the
      two free radical scavengers. After 30 min, the gerbils were exposed to 90-100% O2
      for 24 h. For the spin labeling experiments, cortical synaptosomes were isolated
      from gerbils. The membrane proteins were spin labeled with the thiol-specific
      label MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl). As in our earlier
      study, the EPR spectral parameter of MAL-6-labeled membranes, the W/S ratio,
      decreased with hyperoxia (p < 0.00001). This effect was lessened significantly
      with administration of PBN (p < 0.0003) or Tempol (p < 0.00003). For the GS and
      protein carbonyl assays, cortical proteins were used. The activity of the GS
      decreased with hyperoxia (p < 0.000005), and this effect likewise was lessened
      with administration of PBN (p < 0.004) or Tempol (p < 0.002). The protein
      carbonyl content increased with hyperoxia (p < 0.0002), and there was a
      protective effect found with Tempol (p < 0.000001). The optimum doses for PBN and
      Tempol were 20 and 5 mg/kg, respectively. The results are discussed with
      reference to the use of free radical scavengers as potential antiaging agents.

PMID- 8863513
TI  - Inosine mediates the protective effect of adenosine in rat astrocyte cultures
      subjected to combined glucose-oxygen deprivation.
AB  - Preliminary evidence suggests adenosine, a neuromodulator, has neuroprotective
      properties during cerebral ischemia. It is unclear, however, if adenosine has
      glioprotective effects. We studied the effect of adenosine on cellular injury in
      astroglial cultures subjected to combined glucose-oxygen deprivation. Adenosine
      (100-1,000 microM)dramatically reduced astroglial injury, whereas the adenosine
      agonists 2-chloroadenosine (10 nM-100 microM), N6-cyclopentyladenosine (1 nM-10
      microM), 5'-N-ethylcarboxamidoadenosine (10 nM-100 microM), and N6-2-(4
      aminophenyl)ethyladenosine (10 nM-100 microM) had no effect. Furthermore, the
      adenosine antagonists 8-cyclopentyl-1,3-dipropylxanthine (1 nM-1 microM),
      xanthine amine congener (10 nM-10 microM), and 8-(p-sulfophenyl)-theophylline (10
      300 microM) failed to reverse the protective effect of 200 microM adenosine.
      Next, adenosine degradation products were studied. Inosine proved to be
      glioprotective at concentrations nearly identical to those of adenosine, but
      hypoxanthine and ribose had no effect. The protective effect of 200 microM
      inosine was not reversed by 8-(p-sulfophenyl)theophylline (10-300 microM).
      Adenosine deaminase (1 unit/ml) had no effect on protection produced by
      adenosine, whereas erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (10 microM)
      reversed the protective effect of adenosine. Dipyridamole (4 microM) inhibited
      the protective effect of both adenosine and inosine. We conclude that adenosine
      dramatically decreases astroglial injury during combined glucose-oxygen
      deprivation and that this protective effect appears to be mediated by inosine.

PMID- 8863514
TI  - In vivo tryptophan hydroxylase activity in rat major cerebral arteries is
      decreased by dorsal raphe nucleus lesions.
AB  - The in vivo presence of tryptophan hydroxylase activity in rat major cerebral
      arteries as well as the possible origin of the structure containing it were
      explored. Enzyme activity was appraised by accumulation of 5-hydroxytryptophan
      after inhibition of aromatic L-amino acid decarboxylase. Decarboxylase inhibition
      evoked a significant increase in 5-hydroxytryptophan levels in rat cerebral
      arteries, striatum, hippocampus, hypothalamus, and plasma but had no effect on
      aorta. p-Chlorophenylalanine reduced 5-hydroxytryptophan accumulation in the
      cerebral vessels and brain nuclei, whereas alpha-methyltyrosine did not modify it
      except in hypothalamus, where it was enhanced. alpha-Methyltyrosine significantly
      reduced noradrenaline levels in cerebral arteries and L-dopa accumulation after
      inhibition of the decarboxylase in striatum. Dorsal raphe nucleus lesioning
      significantly diminished 5-hydroxytryptophan formation in cerebral arteries,
      striatum, and hypothalamus, without affecting it in hippocampus. Lesion of median
      raphe nucleus reduced 5-hydroxytryptophan accumulation in hippocampus and in
      hypothalamus but not in cerebral blood vessels or striatum. Superior cervical
      ganglia removal decreased noradrenaline levels in cerebral blood vessels without
      affecting 5-hydroxytryptophan accumulation. These results indicate the presence
      of a functionally active tryptophan hydroxylase in rat cerebral arteries
      associated with fibers originating from dorsal raphe nucleus. This supports that
      rat major cerebral arteries receive serotonergic innervation from central origin.

PMID- 8863515
TI  - Expression, catalytic activity, and inducibility of cytochrome P450 2E1 (CYP2E1)
      in the rat central nervous system.
AB  - Cytochrome P450 2E1 (CYP2E1) metabolizes several neuroactive substrates,
      including exogenous compounds such as anesthetics, organic solvents, and muscle
      relaxants as well as endogenous substrates such as arachidonic acid. CYP2E1 and
      its mRNA were found to be expressed in the rat hippocampus, where the enzyme was
      localized mainly to the microsomal fraction. Chlorzoxazone (CZN), a CYP2E1
      substrate, was 6-hydroxylated in hippocampal homogenates with a K(m) of 25.5
      microM and a Vmax of 0.22 pmol/mg/min. CYP2E1 was also expressed in vitro in
      cortical glial cultures, where CYP2E1 mRNA levels were found to be 1,000-fold
      lower than in rat liver. Exposure of cortical glial cultures to 25 or 100 mM
      ethanol for 24 h caused a fourfold and sixfold increase, respectively, in the
      rate of CYP2E1-dependent 6-hydroxylation of CZN. After a continuous exposure to
      100 mM ethanol for 48 or 72 h, however, the hydroxylation rate was down
      regulated. Chlormethiazole, a potent inhibitor of hepatic CYP2E1 transcription,
      inhibited the ethanol-dependent induction of CYP2E1 by 50%. In vivo, acute
      ethanol treatment of rats (24 h, 3 g/kg) resulted in a 1.8-fold increase in the
      rate of CZN 6-hydroxylation in hippocampal homogenates. It is concluded that
      CYP2E1 is expressed and catalytically active in the rat CNS, and that CYP2E1 can
      be induced by a relatively low concentration of ethanol in cortical glial
      cultures. It is suggested that CYP2E1 substrates may be metabolically activated
      in situ in the CNS.

PMID- 8863516
TI  - Amyloid beta toxicity consists of a Ca(2+)-independent early phase and a Ca(2+)
      dependent late phase.
AB  - Amyloid beta protein (A beta), which accumulates in the senile plaques in the
      brain of Alzheimer's patients, is cytotoxic to neurons. A modified 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, in which a
      yellow redox dye, MTT, is reduced to purple formazan, is very sensitive to the
      effect of A beta. In primary hippocampal cultures, inhibition of MTT reduction
      starts within 2 h after the addition of low concentrations of A beta and reaches
      a plateau in 12 h. This effect of A beta is not blocked by Ca2+ channel blockers
      or in Ca(2+)-free medium. In contrast, lactate dehydrogenase (LDH) release and
      trypan blue exclusion, which are indices of cell death, start 3 days after
      exposure to high concentrations of A beta and are blocked by Ca2+ channel
      blockers such as Co2+, nicardipine, and diltiazem. When A beta was washed out
      from the medium after 12 h, MTT reduction recovers and LDH release does not
      occur, suggesting that a long-lasting inhibition of the cellular redox system may
      be required to induce cell death. These observations demonstrate that A beta
      toxicity consists of two phases-a Ca(2+)-independent early phase and a Ca(2+)
      dependent late phase- and that the early phase may be required to induce the late
      phase.

PMID- 8863517
TI  - Attenuation of cyclic AMP production by carbamazepine.
AB  - The anticonvulsant carbamazepine is an effective treatment both for epilepsy and
      for bipolar affective disorder, but the molecular mechanism(s) underlying its
      therapeutic effects have not been identified. We have found that carbamazepine
      exerts significant inhibitory effects on the cyclic AMP (cAMP) generating system.
      Within the clinical therapeutic range (approximately 50 microM), carbamazepine
      inhibited both basal and forskolin-stimulated cAMP production, without having any
      significant effects on phosphodiesterase activity. Carbamazepine also exerted its
      inhibitory effects on the cAMP generating system in pertussis toxin-treated
      cells, suggesting that the action of carbamazepine was likely mediated through an
      inhibitory guanine nucleotide binding protein-independent mechanism. A forskolin
      affinity purification column was used to purify adenylyl cyclases from rat
      cerebral cortex, and we found that carbamazepine inhibited both basal and
      forskolin-stimulated activity of purified adenylyl cyclase. We also investigated
      the effects of carbamazepine on the levels of the transcription factor, cAMP
      response element binding protein in the phosphorylated (active) state, and found
      that carbamazepine significantly inhibited forskolin-induced phosphorylation of
      the cAMP response element binding protein. The data indicate that carbamazepine
      inhibits adenylyl cyclase activity as well as the downstream effects of
      activation of adenylyl cyclase.

PMID- 8863519
TI  - Two amino acid differences in the sixth transmembrane domain are partially
      responsible for the pharmacological differences between the 5-HT1D beta and 5
      HT1E 5-hydroxytryptamine receptors.
AB  - 5-Hydroxytryptamine elicits its physiological effects by interacting with a
      diverse group of receptors. Two of these receptors, the 5-HT1D beta and the 5
      HT1E receptors, are approximately 60% identical in the transmembrane domains that
      presumably form the ligand binding site yet have very different pharmacological
      properties. Analysis of the pharmacological properties of a series of chimeric 5
      HT1D beta/5-HT1E receptors indicates that sequences in the sixth and seventh
      transmembrane domains are responsible for the differential affinity of 5
      carboxamidotryptamine for these two receptors. More detailed analysis shows that
      two amino acid differences in the sixth transmembrane domain (Ile333 and Ser334
      in the 5-HT1D beta receptor, corresponding to Lys310 and Glu311 in the 5-HT1E
      receptor) are largely responsible for the differential affinities of some, but
      not all, ligands for the 5-HT1D beta and 5-HT1E receptors. It is likely that
      these two amino acids subtly determine the overall three-dimensional structure of
      the receptor rather than interact directly with individual ligands.

PMID- 8863518
TI  - Neurotransmitter-mediated regulation of brain aromatase: protein kinase C- and G
      dependent induction.
AB  - Aromatase in the diencephalic neurons, the level of which increases transiently
      during the prenatal to neonatal period, has been suggested to be involved in
      control of sexual behavior and differentiation of the CNS. Effects of
      neurotransmitters on levels of aromatase mRNA in cultured neurons were
      investigated to determine factors regulating the developmental increase that
      occurs in level of fetal brain aromatase. The expression of aromatase in
      diencephalic neurons of fetal mice at embryonic day 13, cultured in vitro, was
      significantly affected by alpha 1-adrenergic receptor ligands. Aromatase mRNA
      levels were higher in neurons treated with the alpha 1-agonist phenylephrine than
      in control neurons, whereas prazosin, an alpha 1-antagonist, suppressed this
      increase, and ligands for alpha 2- or beta-adrenergic receptors did not exert any
      influence. The profile of alpha 1-adrenergic receptor subtypes during actual
      development in vivo suggested that the alpha 1B subtype is in fact responsible
      for the signal transduction. Substance P, cholecystokinin, neurotensin, and brain
      natriuretic peptide also increased the level of expression along with phorbol 12
      myristate 13-acetate and dibutyrylcyclic GMP, whereas forskolin and dibutyryl
      cyclic AMP caused a decrease. These data indicate that stimulation via alpha 1
      (possibly alpha 1B)-adrenergic receptors, as well as receptors of specific
      neuropeptides, controls the expression of aromatase in embryonic day 13
      diencephalic neurons through activation of protein kinase C or G. beta-Adrenergic
      receptors would not appear to participate in the regulation, judging from their
      developmental profile, although cyclic AMP might be a suppressive second
      messenger.

PMID- 8863520
TI  - Structure of the C-terminal tail of alpha-tubulin: increase of heterogeneity from
      newborn to adult.
AB  - A combination of posttranslational modifications contributes to the high
      heterogeneity of brain tubulin in mammals. In this report, the structures of the
      detyrosinated carboxy-terminal peptides of alpha-tubulin from newborn and adult
      mouse brain were compared. The heterogeneity of these carboxy-terminal peptides
      was observed to increase from newborn to adult brain tubulin. The major part of
      this increased heterogeneity is due to the post-translational excision of Glu450,
      which makes alpha-tubulin nontyrosinatable (delta-2 tubulin). The structures of
      the polyglutamyl side chain of the bi- and triglutamylated peptides were analyzed
      in this work. In polyglutamylation of alpha-tubulin, the first glutamyl residue
      can only be amide-linked to the gamma-carboxyl group of Glu445, but the
      additional residues may be linked either to the gamma- or to the alpha-carboxyl
      groups of the preceding one. By optimized reverse-phase separations and
      comparison with synthetic peptides corresponding to all possible linkages for the
      biglutamylated (gamma 1 alpha 2, gamma 1 gamma 2) and triglutamylated (gamma 1
      alpha 2 alpha 3, gamma 1 gamma 2 gamma 3, gamma 1 alpha 2 gamma 3, gamma 1 gamma
      2 alpha 3, gamma 1 gamma 2 alpha 2) tubulin peptides, it was possible to conclude
      that the mode of linkage connecting the second and third additional glutamyl
      residues corresponds mostly to alpha-bond structures, for both newborn and adult
      mice.

PMID- 8863521
TI  - Existence of two acetylcholinesterases in the mosquito Culex pipiens
      (Diptera:Culicidae).
AB  - Two acetylcholinesterases (AChEs), AChE1 and AChE2, differing in substrate
      specificity and in some aspects of inhibitor sensitivity, have been characterized
      in the mosquito Culex pipiens. The results of ultracentrifugation in sucrose
      gradients and nondenaturing gel electrophoresis of AChE activity peak fractions
      show that each AChE is present as two molecular forms: one amphiphilic dimer
      possessing a glycolipid anchor and one hydrophilic dimer that does not interact
      with nondenaturing detergents. Treatment by phosphatidylinositol-specific
      phospholipase C converts each type of amphiphilic dimer into the corresponding
      hydrophilic dimer. Molecular forms of AChE1 have a lower electrophoretic mobility
      than those of AChE2. However, amphiphilic dimers and hydrophilic dimers have
      similar sedimentation coefficients (5.5S and 6.5S, respectively). AChE1 and AChE2
      dimers, amphiphilic or hydrophilic, resist dithiothreitol reduction under
      conditions that allow reduction of Drosophila AChE dimers. In the insecticide
      susceptible strain S-LAB, AChE1 is inhibited by 5 x 10(-4) M propoxur (a
      carbamate insecticide), whereas AChE2 is resistant. All animals are killed by
      this concentration of propoxur, indicating that only AChE1 fulfills the
      physiological function of neurotransmitter hydrolysis at synapses. In the
      insecticide-resistant strain, MSE, there is no mortality after exposure to 5 x
      10(-4) M propoxur: AChE2 sensitivity to propoxur is unchanged, whereas AChE1 is
      now resistant to 5 x 10(-4) M propoxur. The possibility that AChE1 and AChE2 are
      products of tissue-specific posttranslational modifications of a single gene is
      discussed, but we suggest, based on recent results obtained at the molecular
      level in mosquitoes, that they are encoded by two different genes.

PMID- 8863522
TI  - p-Chlorophenylalanine-induced alteration of somatodendritic levels of tryptophan
      hydroxylase within the rat mesencephalic raphe nuclei.
AB  - Tryptophan hydroxylase distribution was examined across the nuclei raphe
      dorsalis, medianus, and pontis of the adult rat, under basal conditions and 2
      days after a single injection of p-chlorophenylalanine, an irreversible
      tryptophan hydroxylase inhibitor. Tryptophan hydroxylase-expressing cells were
      numbered in transverse sections processed for immunohistochemistry, and the area
      of tryptophan hydroxylase distribution was delineated in adjacent sections
      transferred onto nitrocellulose and processed for immunoautoradiography. Two
      distinct areas were visualized: an inner zone, corresponding to the area
      displaying tryptophan hydroxylase-immunoreactive cells (so-called somatic area),
      and an outer zone, here called perisomatic, devoid of perikarya yet rich in
      tryptophan hydroxylase-positive neuropil in the histological sections. After
      treatment with p-chlorophenylalanine, a significant decrease in the number of
      tryptophan hydroxylase-immunoreactive cells could be observed only in the rostral
      raphe dorsalis, particularly within its ventromedian and dorsomedian
      subdivisions. In all raphe nuclei, the topological reconstruction of the somatic
      area was not modified. Based on the densitometric measurements in the
      immunoautoradiographs, however, a dramatic decrease in the content,
      concentration, and volume of expression of tryptophan hydroxylase could be
      documented in the three raphe nuclei. Detailed analysis of these results led to
      the conclusion that (a) tryptophan hydroxylase expression is differentially
      regulated in different serotoninergic cell body subpopulations of the raphe, some
      of which are more sensitive to p-chlorophenylalanine, and (b) distribution of
      tryptophan hydroxylase protein is modified also in the somatodendritic area in
      all raphe nuclei.

PMID- 8863523
TI  - Rate of retrograde transport of cholera toxin from the plasma membrane to the
      Golgi apparatus and endoplasmic reticulum decreases during neuronal development.
AB  - Various glycolipid-binding toxins are internalized from the cell surface to the
      Golgi apparatus. Prominent among these is cholera toxin (CT), which consists of a
      pentameric B subunit that binds to ganglioside GM1 and an A subunit that mediates
      toxicity. We now demonstrate that rhodamine (Rh)-CT can be further internalized
      from the Golgi apparatus to the endoplasmic reticulum (ER) in cultured
      hippocampal neurons and in neuroblastoma N18TG-2 cells and that the A subunit is
      essential for retrograde transport to the ER. In addition, the rate of
      internalization of Rh-CT to the Golgi apparatus and ER decreases dramatically as
      hippocampal neurons mature. The Golgi apparatus was labeled in almost all 1-day
      old neurons after < 1 h of incubation with Rh-CT but was labeled in < 10% of 14
      day-old neurons after 1 h. During the first 14 days in culture, there was a 15
      fold increase in the number of 125I-CT-binding sites per cell, indicating that
      the decrease in the rate of internalization of Rh-CT is not due to reduced levels
      of cell surface GM1 in older neurons. These results imply that the rate of
      retrograde transport of CT from the plasma membrane to the Golgi apparatus and ER
      is regulated during neuronal development and differentiation.

PMID- 8863524
TI  - Unsaturated free fatty acids increase benzodiazepine receptor agonist binding
      depending on the subunit composition of the GABAA receptor complex.
AB  - It has been shown previously that unsaturated free fatty acids (FFAs) strongly
      enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor
      ligands in the CNS in vitro. To investigate the selectivity of this effect,
      recombinant human GABAA/benzodiazepine receptor complexes formed by different
      subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and
      3) were expressed using the baculovirus-transfected Sf9 insect cell system. At
      10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic
      (22:6) acids, strongly stimulated (> 200% of control values) the binding of
      [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in
      whole cell preparations. No effect or small increases in levels of unsaturated
      FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2
      receptor combinations were observed, and weak effects (130% of control values)
      were detected using the alpha 5 beta 2 gamma 2 receptor combination. The
      saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM
      binding to any combination of receptor complexes. The hydroxylated unsaturated
      FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of
      [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given
      the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in
      the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to
      vary at both cellular and regional levels.

PMID- 8863525
TI  - Preparation of giant myelin vesicles and proteoliposomes to register ionic
      channels.
AB  - Myelin vesicles, reconstituted liposomes with proteolipid protein (PLP), the main
      protein component of myelin, and electrophysiological patch-clamp are potentially
      powerful tools to study the role of myelin in functional ionic channels. However,
      technical difficulties in the vesiculation of myelin and the small size of the
      vesicles obtained do not permit the application of micropipettes for current
      recordings. From a suspension of purified myelin we have prepared oligolamellar
      vesicles (mean diameter of 144 nm) using the so-called French pressure system.
      From this preparation we obtained giant myelin vesicles approximately 10 microns
      in mean diameter, using a dehydration-rehydration procedure. Qualitative analysis
      of proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed
      no significant loss of any component in these vesicles due to pressure, in
      comparison with non-vesiculated myelin. A way of preparing giant liposomes of
      approximately 80-100 microns and proteoliposomes of approximately 30 microns in
      mean diameter, using the same dehydration-rehydration procedure, is also
      reported. Reconstitution of purified PLP in giant liposomes was confirmed by
      fluorescent labeling of PLP and by fluorescence microscopy. The current
      recordings from these vesicles prove the validity of these methods and provide
      significant evidence of the existence of ionic channels in myelin membranes and
      the possibility that PLP functions as a channel. The physiological significance
      and characterization of these channels remain yet unresolved. These results have
      a special significance for elucidating the molecular role of myelin in the
      regulation of neural activity and in the brain ion microenvironment.

PMID- 8863526
TI  - Novel omega-conotoxins block dihydropyridine-insensitive high voltage-activated
      calcium channels in molluscan neurons.
AB  - We have identified two novel peptide toxins from molluscivorous Conus species
      that discriminate subtypes of high voltage-activated (HVA) calcium currents in
      molluscan neurons. The toxins were purified using assays on HVA calcium currents
      in the caudodorsal cells (CDCs) of the snail Lymnaea stagnalis. The CDC HVA
      current consists of a rapidly inactivating, transient current that is relatively
      insensitive to dihydropyridines (DHPs) and a slowly inactivating, DHP-sensitive L
      current. The novel toxins, designated omega-conotoxins PnVIA and PnVIB,
      completely and selectively block the transient HVA current in CDCs with little
      (PnVIA) or no (PnVIB) effect on the sustained L-type current. The block is rapid
      and completely reversible. It is noteworthy that both PnVIA and PnVIB reveal very
      steep dose dependences of the block, which may imply cooperativity in toxin
      action. The amino acid sequences of PnVIA (GCLEVDYFCGIPFANNGLCCSGNCVFVCTPQ) and
      of PnVIB (DDDCEPPGNFCGMIKIGPPCCSGWCFFACA) show very little homology to previously
      described omega-conotoxins, although both toxins share the typical omega
      conotoxin cysteine framework but have an unusual high content of hydrophobic
      residues and net negative charge. These novel omega-conotoxins will facilitate
      selective analysis of the functions of HVA calcium channels and may enable the
      rational design of drugs that are selective for relevant subtypes.

PMID- 8863527
TI  - Effect of buthionine sulfoximine, a synthesis inhibitor of the antioxidant
      glutathione, on the murine nigrostriatal neurons.
AB  - This study analyzed the effects of acute systemic treatment with buthionine
      sulfoximine (BSO), a synthesis inhibitor of the antioxidant reduced glutathione
      (GSH), on dopaminergic neurons of the murine nigrostriatal pathway. Part 1 of the
      study established a dose-response curve and the temporal pattern of GSH loss and
      recovery in the substantia nigra and striatum following acute BSO treatment. Part
      2 of the study determined the effect of acute BSO treatment on the morphology and
      biochemistry of nigrostriatal neurons. We found that decreases in GSH levels had
      profound morphological effects, including decreased catecholamine fluorescence
      per cell, increased levels of lipid peroxidation and lipofuscin accumulation, and
      increased numbers of dystrophic axons in dopaminergic neurons of the
      nigrostriatal pathway. However, no measurable effects were observed in
      biochemical levels of either dopamine or its metabolites. These changes mimic
      those that have been reported to occur in the nigrostriatal system of rodents
      with advancing age. Our data suggest that reduction of GSH via BSO treatment
      results in the same types of nigrostriatal degenerative effects that occur during
      the aging process and consequently is a good model system for examining the role
      of GSH in protecting this area of the brain against the harmful effects of age
      related oxidative stress.

PMID- 8863528
TI  - Characterisation and molecular identification of adrenomedullin binding sites in
      the rat spinal cord: a comparison with calcitonin gene-related peptide receptors.
AB  - Calcitonin gene-related peptide (CGRP) and its receptors are found in mammalian
      spinal cord. We show, for the first time, binding sites for the novel related
      peptide adrenomedullin in rat spinal cord microsomes. 125I-Adrenomedullin binding
      showed high affinity (KD = 0.45 +/- 0.06 nM) and sites were abundant (Bmax = 723
      +/- 71 fmol/mg of protein). CGRP, amylin, and calcitonin did not compete at these
      sites (Ki > 10 microM). High-affinity CGRP binding sites (KD = 0.18 +/- 0.01 nM)
      were much less numerous (Bmax = 17.7 +/- 2.4 fmol/mg of protein) and showed
      competition by unlabeled adrenomedullin (Ki = 34.6 +/- 2.4 nM). Chemical cross
      linking revealed a major band for 125I-adrenomedullin of M(r) = 84,400 +/- 1,200
      and a minor band of M(r) = 122,000 +/- 8,700. 125I-CGRP cross-linking showed
      bands of lower molecular weight (M(r) = 74,500 +/- 5,000 and 61,000 +/- 2,200).
      Enzymic deglycosylation of the adrenomedullin binding site showed a considerable
      carbohydrate content. Neither adrenomedullin nor CGRP was able to increase cyclic
      AMP in spinal cord. Adrenomedullin mRNA was present in spinal cord, at one-third
      of its level in lung, and adrenomedullin immunoreactivity was present, at a low
      concentration (40 fmol/g of tissue). Thus, the presence of abundant binding sites
      and adrenomedullin mRNA and immunoreactivity anticipate an as yet undefined
      function for this peptide in spinal cord.

PMID- 8863529
TI  - Preferential release of ATP and its extracellular catabolism as a source of
      adenosine upon high- but not low-frequency stimulation of rat hippocampal slices.
AB  - The release of adenosine and ATP evoked by electrical field stimulation in rat
      hippocampal slices was investigated with the following two patterns of
      stimulation: (1) a brief, high-frequency burst stimulation (trains of stimuli at
      100 Hz for 50 ms applied every 2 s for 1 min), to mimic a long-term potentiation
      (LTP) stimulation paradigm, and (2) a more prolonged (3 min) and low-frequency (5
      Hz) train stimulation, to mimic a long-term depression (LTD) stimulation
      paradigm. The release of ATP was greater at a brief, high-frequency burst
      stimulation, whereas the release of [3H]adenosine was slightly greater at a more
      prolonged and low-frequency stimulation. To investigate the source of
      extracellular adenosine, the following two pharmacological tools were used:
      alpha, beta-methylene ADP (AOPCP), an inhibitor of ecto-5'-nucleotidase, to
      assess the contribution of the catabolism of released adenine nucleotides as a
      source of extracellular adenosine, and S-(4-nitrobenzyl)-6-thioinosine (NBTI), an
      inhibitor of adenosine transporters, to assess the contribution of the release of
      adenosine, as such, as a source of extracellular adenosine. At low-frequency
      stimulation, NBTI inhibited by nearly 50% the evoked outflow of [3H]-adenosine,
      whereas AOPCP inhibited [3H]adenosine outflow only marginally. In contrast, at
      high-frequency stimulation, AOPCP inhibited by 30% the evoked release of
      [3H]adenosine, whereas NBTI produced a 40% inhibition of [3H]adenosine outflow.
      At both frequencies, the kinetics of evoked [3H]adenosine outflow was affected in
      different manners by AOPCP and NBTI; NBTI mainly depressed the rate of evoked
      [3H]adenosine outflow, whereas AOPCP mainly inhibited the later phase of evoked
      [3H]adenosine accumulation. These results show that there is a simultaneous, but
      quantitatively different, release of ATP and adenosine from rat hippocampal
      slices stimulated at frequencies that can induce plasticity phenomena such as LTP
      (100 Hz) or LTD (5 Hz). The source of extracellular adenosine is also different
      according to the frequency of stimulation; i.e., at a brief, high-frequency
      stimulation there is a greater contribution of released adenine nucleotides for
      the formation of extracellular adenosine than at a low frequency with a more
      prolonged stimulation.

PMID- 8863530
TI  - Neural thrombin and protease nexin I kinetics after murine peripheral nerve
      injury.
AB  - We addressed the balance between thrombin and its serpin protease nexin I (PNI)
      after sciatic nerve injury in the mouse. Prothrombin levels increased twofold 24
      h after nerve crush, as measured by a specific chromogenic assay, and peaked at
      day 3. Thrombin activity also increased 2-4 days after injury in distal sciatic
      nerve segments. Nerve RNA analysis using reverse transcriptase--polymerase chain
      reaction (RT-PCR) assay confirmed that prothrombin was synthesized locally. We
      also monitored PNI levels in these injured nerve samples by complex formation
      with an 125I-labeled target protease and found peak activity occurring later, 6-9
      days after the thrombin induction. These data indicate that nerve injury first
      induces the synthesis of prothrombin, which is subsequently converted to active
      thrombin. Nerve crush-induced thrombin is followed by the generation of
      functionally active PNI and may be directly responsible for its induction. By
      immunocytochemistry with anti-PNI antibody, we found that activated Schwann cells
      were the source of induced PNI. These results support the concept that the
      balance between serine proteases and their serpins is dysregulated during nerve
      injury and suggests a role for its reestablishment in nerve damage repair.

PMID- 8863531
TI  - Cloning of CDP-diacylglycerol synthase from a human neuronal cell line.
AB  - A critical step in the supply of substrate for the phosphoinositide signal
      transduction pathway is the formation of the liponucleotide intermediate, CDP
      diacylglycerol, catalyzed by CDP-diacylglycerol synthase. Further insight into
      the regulation of phosphoinositide biosynthesis was sought by cloning of the gene
      for the vertebrate enzyme. Sequence of the corresponding gene from Drosophila was
      used to prepare a probe for screening of a human neuronal cell cDNA library. A
      cDNA was isolated with a predicted open reading frame of 1,332 bases, encoding a
      protein of 51 kDa. The amino acid sequence showed 50% identity (75% similarity)
      to that of Drosophila eye CDP-diacylglycerol synthase and substantial similarity
      to the Saccharomyces cerevisiae and Escherichia coli homologues. Northern blot
      analysis, with human cDNA riboprobes, suggested that the corresponding mRNA was
      expressed in all human tissues examined. Expression of the human cDNA in COS
      cells resulted in a more than fourfold increase in CDP-diacylglycerol synthase
      activity. Knowledge of the sequence of vertebrate CDP-diacylglycerol synthase
      should facilitate further investigations into its regulation and the possible
      existence of distinct isoforms.

PMID- 8863532
TI  - Combined administration of a 5-hydroxytryptamine (5-HT)1D antagonist and a 5-HT
      reuptake inhibitor synergistically increases 5-HT release in guinea pig
      hypothalamus in vivo.
AB  - In vivo microdialysis in guinea pig hypothalamus was used to study the effect of
      serotonin [5-hydroxytryptamine (5-HT)] subtype 1D autoreceptor blockade on the
      increase in extracellular 5-HT levels produced by a selective 5-HT reuptake
      inhibitor (SSRI). Administration of the selective 5-HT1D antagonist GR127935 at
      0.3 mg/kg had no effect, but 5 mg/kg significantly increased extracellular levels
      of 5-HT and 5-hydroxyindoleacetic acid to 135% of basal values. Moreover, at
      these doses GR127935 significantly attenuated the decrease in extracellular 5-HT
      levels following local perfusion with the selective 5-HT1D agonist CP-135,807.
      The SSRI sertraline at 2 mg/kg increased 5-HT levels to 130% of basal levels. The
      combination of this low dose of sertraline with either dose of GR127935 resulted
      in a pronounced, long-lasting increases in 5-HT levels to 230% of basal values.
      These results indicate that the effects of an SSRI on terminal 5-HT are
      significantly enhanced by coadministration of a 5-HT1D antagonist and confirm
      that in addition to somatodendritic 5-HT1A autoreceptors, terminal 5-HT1D
      autoreceptors mitigate the effect of SSRIs on terminal 5-HT. As such, antagonists
      of the 5-HT1D autoreceptor could be useful as rapidly acting antidepressants and
      may shorten the onset of antidepressant action when combined with SSRIs.

PMID- 8863533
TI  - Scavenging effects of dopamine agonists on nitric oxide radicals.
AB  - It has recently been considered that free radicals are closely involved in the
      pathogenesis of Parkinson's disease (PD), and the level of nitric oxide radical
      (.NO), one of the free radicals, is reported to increase in PD brain. In the
      present study, we established a direct detection system for .NO in an in vitro
      .NO-generating system using 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N
      methyl-1-propa namine as an .NO donor and 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO) by electron spin resonance
      (ESR) spectrometry and examined the quenching effects of the dopamine agonists
      pergolide and bromocriptine on the amount of.NO generated. .NO appeared to be
      scavenged by pergolide and, to a lesser extent, by bromocriptine. In the
      competition assay, the 50% inhibitory concentration values for pergolide and
      bromocriptine were estimated to be approximately 23 and 200 microM, respectively.
      It was previously reported that in vivo treatment of pergolide and bromocriptine
      completely protected against the decrease in levels of striatal dopamine and its
      metabolites in the 6-hydroxydopamine-injected mouse. Considering these findings,
      pergolide and probably bromocriptine may also protect against dysfunction of
      dopaminergic neurons because of its multiple effects; not only does it stimulate
      the presynaptic autoreceptors, but it also directly scavenges .NO radicals and
      hence protects against .NO-related cytotoxicity. This ESR spectrometry method
      using carboxy-PTIO may be useful for screening other drugs that can quench .NO.

PMID- 8863534
TI  - Expression of native GABAA receptors in Xenopus oocytes injected with rat brain
      synaptosomes.
AB  - Oocytes from the frog Xenopus laevis were shown recently to express native
      nicotinic acetylcholine receptors after injection with purified Torpedo
      electroplaque membrane vesicles. Injection of Xenopus oocytes with rat cortical
      or nigral synaptosomes has now been shown to result in the expression of gamma
      aminobutyric acid type A (GABAA) receptor-mediated Cl- currents.
      Electrophysiological characterization of the responses of these receptors to GABA
      and other agents revealed that they were incorporated into the oocyte membrane
      and that they retained their original pharmacological properties, such as
      sensitivity to Cl- channel blockers, benzodiazepines, and general anesthetics.
      These results suggest that this approach to the expression of heterologous
      proteins in Xenopus oocytes may facilitate the study of native synaptic proteins
      derived from brain tissue.

PMID- 8863535
TI  - Intracerebral NMDA injection stimulates production of interleukin-1 beta in
      perinatal rat brain.
AB  - Susceptibility to NMDA neurotoxicity peaks in the early postnatal period in rats.
      Although indirect evidence suggests that interleukin-1 beta is a mediator of NMDA
      neurotoxicity in perinatal rats, direct confirmation of NMDA-induced interleukin
      1 beta production in the brain has not been reported previously. The primary goal
      of this study was to determine if intracerebral injection of a neurotoxic dose of
      NMDA stimulates interleukin-1 beta production acutely. We used a rat-specific
      interleukin-1 beta ELISA to quantify brain tissue homogenate interleukin-1 beta
      content, and an immunocytochemical assay with a monoclonal antirat interleukin-1
      beta antibody to visualize its distribution. NMDA (10 nmol) was injected
      stereotaxically into 7-day-old rats, using coordinates that targeted the striatum
      and overlying dorsal hippocampus. Interleukin-1 beta concentrations were measured
      in samples from the injected and contralateral cerebral hemispheres 0-12 h later;
      In addition, the impact of treatment with the noncompetitive NMDA antagonist MK
      801 on interleukin-1 beta production was assessed. We found marked increases in
      tissue content of interleukin-1 beta in the lesioned hemisphere; values peaked at
      6 h post injection. Treatment with MK-801 (1 mg/kg) blocked NMDA-induced
      increases in interleukin-1 beta. Preliminary immunocytochemical analysis
      demonstrated high concentrations of interleukin-1 beta-immunoreactive cells in
      the lesioned hippocampus, and concurrent increases in interleukin-1 beta
      immunoreactivity diffusely in the ependyma at 6 h after NMDA administration. Our
      data provide the first direct evidence that NMDA-induced excitotoxic injury
      stimulates interleukin-1 beta production in vivo.

PMID- 8863536
TI  - Investigation of myelin/oligodendrocyte glycoprotein membrane topology.
AB  - Myelin/oligodendrocyte glycoprotein (MOG) is a CNS-specific integral membrane
      protein that is an atypical member of the immunoglobulin (Ig) superfamily with
      two potential transmembrane domains based upon hydropathy analysis. With only one
      other exception, all Ig family members possess a single or no membrane spanning
      region. In order to analyze MOG membrane topology, we prepared stably transfected
      cells that express mouse MOG and used three domain-specific antisera to ascertain
      the localization of these hydrophobic domains. As expected, MOG's glycosylated N
      terminal Ig-like domain was identified as extracellular, because membrane
      permeabilization was not required for immunoreactivity with the MOG1-125
      antiserum. In contrast, both MOG154-169 and MOG198-218 antisera stained cells
      only upon permeabilization. These data indicate that only MOG's N-terminal
      hydrophobic domain spans the lipid bilayer, and we propose that MOG's C-terminal
      hydrophobic domain associates with the cytoplasmic face of the plasma membrane.
      As for MOG's second hydrophobic domain, it is clear that either orientation
      (transmembrane versus membrane-associated) would be unique among Ig-like
      proteins, and the implications of our proposed topology for MOG in
      oligodendroglial plasma membrane are discussed.

PMID- 8863537
TI  - Tropism in bacterial infections: urinary tract infections.
AB  - PURPOSE: Tropism describes the phenomenon by which commensal and pathogenic
      bacteria are restricted to certain hosts, tissue and cell types. This review was
      done to shed light on the initiating factors in bacterial disease, more
      particularly those responsible for urinary tract infections. MATERIALS AND
      METHODS: The literature was reviewed on the tropism of several common bacterial
      infections with an extensive evaluation of tropism at the molecular level in
      urinary tract infections. RESULTS: Interaction of bacteria with certain tissues,
      cells and molecules is described. Initially, bacterial adhesion occurs via
      bacterial fimbriae in the case of gram-negative bacteria, while gram-positive
      bacteria adhere more frequently via extracellular polysaccharides. Urinary tract
      infections occur most frequently because of adherence via P-fimbriae of
      Escherichia coli. P-fimbriae are important in cystitis as well, while type 1
      fimbriae and nonfimbrial adhesins may also be responsible for its initiation.
      CONCLUSIONS: The usual initiating mechanism in bacterial infections involves
      bacterial adhesion to specific molecules on cell surfaces, followed by invasive
      disease. The tip proteins of P-fimbriae of Escherichia coli lead to the
      initiation of urinary tract infection. Understanding the molecular events
      responsible may lead to development of a vaccine to prevent urinary tract
      infection.

PMID- 8863539
TI  - Cost-effectiveness of different treatment options for staghorn calculi.
AB  - PURPOSE: The cost-effectiveness of shock wave lithotripsy monotherapy,
      percutaneous nephrolithotomy and combined sandwich therapy in the treatment of
      staghorn calculi was examined. MATERIALS AND METHODS: The cost-effective index,
      which estimates the average cost of making 1 patient stone-free, was computed for
      the various treatment options. Data for effectiveness of each therapy were used
      as available from the literature. Billing charges were used as cost data from
      University Hospital and the Kidney Stone Center. RESULTS: Average charges for a
      single percutaneous nephrolithotomy were $26,622, of which 81% were facility
      charges and 7.9% urologist fees. Average charges for a single shock wave
      lithotripsy were $8,213, 60.3% of which were facility fees and 33.3% of which
      were urologist charges. Overall, percutaneous nephrolithotomy and combined
      sandwich therapy were more cost-effective than shock wave lithotripsy
      monotherapy. When the stone surface area was less than 500 mm2 combined sandwich
      therapy and shock wave lithotripsy monotherapy were equally cost-effective.
      However, when the stone burden was greater than 500 mm2 combined sandwich therapy
      clearly became more cost-effective than shock wave lithotripsy monotherapy.
      CONCLUSIONS: Percutaneous nephrolithotomy followed by shock wave lithotripsy, if
      necessary, and second look nephroscopy are the most cost-effective methods of
      treating staghorn calculi.

PMID- 8863538
TI  - Quantitative polymerase chain reaction does not improve preoperative prostate
      cancer staging: a clinicopathological molecular analysis of 121 patients.
AB  - PURPOSE: To improve on current staging and monitoring methods for prostate
      cancer, we applied the technique of quantitative polymerase chain reaction to
      measure the degree of tumor burden in the circulation and correlate this with
      pathological tumor stage. A reproducible, highly sensitive and specific, reverse
      transcriptase-polymerase chain reaction amplification technique to quantify
      prostate specific antigen (PSA) and prostate specific membrane antigen gene
      expression in the peripheral circulation was developed. Using a 32phosphorus
      gamma-adenosine triphosphate-5'PSA and prostate specific membrane antigen primer
      incorporation assay, the ribonucleic acid signal extracted from a single
      neoplastic cell (LNCaP) premixed in 10 cc normal whole blood could be amplified.
      PSA and prostate specific membrane antigen polymerase chain reaction indexes have
      been created for clinical application. MATERIALS AND METHODS: From September 1994
      through July 1995 specimens from 121 patients were prospectively analyzed for PSA
      and prostate specific membrane antigen signals. RESULTS: Circulating PSA
      producing cells were present in 29 of 33 patients (88%) with metastatic prostate
      cancer. Two of 19 patients (11%) with no known prostate cancer exhibited positive
      signals (1 later had prostate cancer), establishing a sensitivity of 88% and
      specificity of 94% for our assay. Positive PSA polymerase chain reaction signals
      were detected in 30 of 51 patients (59%) with stages pT1 and pT2 disease and in
      13 of 18 (72%) with stage pT3 cancer. No statistically significant relationship
      of a positive PSA polymerase chain reaction signal to pathological stage, tumor
      grade, apical involvement or positive surgical margins was found, and no benefit
      was derived by measuring the quantity of circulating PSA polymerase chain
      reaction signals. Circulating prostate specific membrane antigen polymerase chain
      reaction signals were identified mostly in patients with advanced prostate cancer
      and offered no benefit to preoperative staging. CONCLUSIONS: Given the high
      incidence of false positive signals in patients with pathologically determined
      localized disease, in our experience polymerase chain reaction based assays offer
      no immediate benefit for preoperative prostate cancer staging. The prognostic
      significance of detecting circulating prostate specific signals awaits longer
      followup in this cohort of patients, which is currently under study.

PMID- 8863540
TI  - Extracorporeal shock wave lithotripsy for lower pole calculi: long-term
      radiographic and clinical outcome.
AB  - PURPOSE: We evaluated the efficacy of extracorporeal shock wave lithotripsy
      (ESWL) for lower pole calculi regarding immediate and long-term radiographic and
      clinical outcomes. MATERIALS AND METHODS: A total of 206 patients with isolated
      lower pole calculi in 220 renal units underwent ESWL for stones 4 to 625 mm2
      (mean 88). Clinical and radiographic followup was obtained at 1 month and every 6
      to 12 months thereafter. An initial stone-free rate was determined, as was the
      subsequent radiographic outcome. Clinical outcome with regard to a symptomatic
      episode or requiring intervention was also determined. Kaplan-Meier estimates of
      the probabilities of these outcomes with time were developed. RESULTS: Of the 206
      patients 99 (48%) were rendered stone-free by 1 month after ESWL. Another 13
      patients (6.3%) spontaneously became stone-free within another 1 to 95 months
      (mean 17.5). Of the remaining patients residual stones were decreased, stable or
      increased in 13 (6.3%), 71 (34%) and 10 (4.8%), respectively, after 1 to 91
      months (mean 14.5). Among all 206 patients 180 (87.4%) remained asymptomatic for
      1 to 99 months, while 7 (3.4%) suffered a symptomatic episode requiring medical
      attention 1 to 40 months (mean 21.1) after ESWL and 19 (9.2%) required
      intervention after 1 to 91 months (mean 23.9). Kaplan-Meier estimates of the
      probabilities of a symptomatic episode or requiring intervention at 5 years were
      0.24 and 0.52, respectively. CONCLUSIONS: ESWL is the initial treatment of choice
      for lower pole calculi smaller than 2 cm.2 because the stone-free rate is
      comparable to that for stones at other caliceal locations and, perhaps more
      importantly, the risk of a symptomatic episode or requiring secondary
      intervention is low even in the setting of residual fragments.

PMID- 8863541
TI  - Medical treatment of cystinuria: results of contemporary clinical practice.
AB  - PURPOSE: We determined the efficacy of a contemporary medical regimen for
      treatment of cystinuria. MATERIALS AND METHODS: A total of 16 patients with
      cystinuria was followed for 7 to 141 months (mean 78.1). Standard therapy
      included hydration and alkalization. D-penicillamine or alpha
      mercaptoproprionylglycine was added for failure of hydration and alkalization to
      prevent new stones or stone growth, or to cause dissolution. Captopril was added
      for failure of or intolerance to D-penicillamine or alpha
      mercaptopropionylglycine. Radiography was performed every 6 to 12 months, at
      which time stone events were documented. RESULTS: During hydration and
      alkalization 46 stone events occurred in 8 of 9 patients (1.6 events per patient
      year). With addition of thiol derivatives 7 of 9 patients experienced 24 stone
      events, all 6 treated with hydration, alkalization and captopril experienced 10
      events, and 4 of 5 treated with alkalization, thiols and captopril experienced 8
      events (0.52, 0.71 and 0.54 events per patient-year, respectively). During a
      total treatment time of 104.1 patient-years 88 stone events occurred in 14 of 16
      patients (0.84 events per patient-year). CONCLUSIONS: D-penicillamine and alpha
      mercaptopropionylglycine are effective in decreasing the rate of stone formation
      in patients in whom hydration and alkalization failed. While captopril may also
      be beneficial in this setting, it does not appear to be as effective as D
      penicillamine or alpha-mercaptopropionylglycine, and it does not clearly add
      clinical benefit to those thiols. Our study demonstrates that patients with
      cystinuria are at high risk for recurrence when treated with any contemporary
      medical program. This natural history must be considered when evaluating the long
      term efficacy of newer or alternative modes of medical and urological treatment.

PMID- 8863542
TI  - Management of stone disease--bearing the burden.

PMID- 8863543
TI  - Intracorporeal electrohydraulic lithotripsy of ureteral and renal calculi using
      small caliber (1.9F) electrohydraulic lithotripsy probes.
AB  - PURPOSE: The development of 1.9F or smaller electrohydraulic lithotripsy probes
      has facilitated the use of this form of lithotripsy via miniature rigid and
      flexible ureteroscopes. We report our experience with ureteroscopic
      intracorporeal lithotripsy using 1.9F electrohydraulic lithotripsy probes.
      MATERIALS AND METHODS: A total of 45 patients (32 ureteral and 57 renal calculi)
      underwent retrograde rigid (microscopic to 6F short) or flexible (7.5 and 9.4F)
      ureteroscopy with electrohydraulic lithotripsy using 1.9F electrohydraulic
      lithotripsy probes. In 17 patients (38%) there were 37 lower pole caliceal
      calculi (41%). Stone size ranged from 3 to 30 mm. (mean 8.5). RESULTS:
      Electrohydraulic lithotripsy resulted in successful fragmentation (that is 2 mm.
      or smaller fragments) in 98% of patients overall. It was successful after failure
      of HM-3 extracorporeal shock wave lithotripsy in 10 patients and after failed
      lithotripsy with the 140 mJ. tunable dye laser in 7. Electrohydraulic lithotripsy
      resulted in successful fragmentation of 94% of lower pole caliceal stones. No
      intraoperative complications and no significant ureteral or renal mucosal damage
      were noted. Fever developed postoperatively in 2 patients (4.4%) with negative
      urine cultures. Postoperatively an indwelling stent was placed for 2 weeks or
      less in 71% of patients and no stents were placed due to preoperative stenting in
      29%. Average hospital stay was 0.8 days (range 0 to 4). Followup imaging in 38
      patients (84%) at a mean of 8.7 months (range 2 to 28) revealed stone-free rates
      of 92% overall and 87% in patients with lower pole renal calculi. No patient had
      a ureteral or infundibular stricture postoperatively. CONCLUSIONS: The
      development of 1.9F or smaller electrohydraulic lithotripsy probes provides the
      urologist with a safe, highly effective and inexpensive method for performing
      intracorporeal lithotripsy throughout the entire upper urinary tract via rigid or
      flexible ureteroscopes. Furthermore, for the ureteroscopic treatment of lower
      pole renal calculi electrohydraulic lithotripsy is the only form of
      intracorporeal lithotripsy sufficiently malleable to allow routine access.

PMID- 8863544
TI  - Renal cell carcinoma metastatic to the lung: potential benefit in the combination
      of biological therapy and surgery.
AB  - PURPOSE: We evaluated outcomes in cases of renal cell carcinoma metastatic to the
      lung treated with surgery or biological therapy followed by surgery. MATERIALS
      AND METHODS: We retrospectively evaluated 22 patients treated with surgical
      resection and 29 treated with biological therapy followed by surgery. RESULTS: At
      the time of this study 31 patients (61%) were alive, including 15 with no
      residual disease and 16 with disease. Of the 22 patients treated with surgery
      without initial biological therapy 12 (55%) were alive at a median followup of 57
      months (range 17 to 148) and 19 of the 29 (66%) treated with combination therapy
      were alive at a median followup of 48 months (range 19 to 78). A total of 19
      patients (37%) died of progressive disease. CONCLUSIONS: Our results suggest a
      role for an aggressive surgical approach in select patients with metastatic renal
      cell carcinoma, and demonstrate that patients who do not achieve a complete
      response to biological therapy may benefit from surgical resection of residual
      disease.

PMID- 8863545
TI  - Laser induced autofluorescence diagnosis of bladder tumors: dependence on the
      excitation wavelength.
AB  - PURPOSE: We assessed the ability of laser induced autofluorescence spectroscopy
      to distinguish neoplastic urothelial bladder lesions from normal or nonspecific
      inflammatory mucosa. MATERIALS AND METHODS: Three different pulsed laser
      excitation wavelengths were used successively: 308 nm. (xenium chloride excimer
      laser), 337 nm. (nitrogen laser) and 480 nm. (coumarin dye laser). The excitation
      light was delivered by a specially devised multifiber catheter connected to a 1
      mm. core diameter silica monofiber introduced through the working channel of a
      standard cystoscope with saline irrigation. The captured fluorescence light was
      focused onto an optical multichannel analyzer detection system. Device
      performance was evaluated in 25 patients after obtaining consent and immediately
      before transurethral resection of a bladder tumor. Spectroscopic results were
      compared with histological findings. RESULTS: At 337 and 480 nm. excitation
      wavelengths the overall fluorescence intensity of bladder tumors was clearly
      decreased compared to normal urothelial mucosa regardless of tumor stage and
      grade. At the 308 nm. excitation wavelength the shape of the tumor spectra,
      including carcinoma in situ, was markedly different from that of normal or
      nonspecific inflammatory mucosa. No absolute intensity determinations were
      required in this situation, since a definite diagnosis could be established based
      on the fluorescence intensity ratio at 360 and 440 nm. CONCLUSIONS: This
      spectroscopic study could be particularly useful to design a simplified
      autofluorescence imaging device for detection of occult urothelial neoplasms.

PMID- 8863546
TI  - Laser induced autofluorescence diagnosis of bladder cancer.
AB  - PURPOSE: We assessed the ability of laser induced autofluorescence to
      differentiate malignant from nonmalignant bladder lesions. MATERIALS AND METHODS:
      We studied 53 patients with bladder cancer undergoing mucosal biopsies or
      transurethral resection of a bladder tumor. A quartz optical fiber was advanced
      through the working channel of a cystoscope and placed in gentle contact with the
      bladder. Tissue fluorescence was excited by 337 nm. light pulses (nitrogen
      laser). One fiber was used for transmission of the excitation and emission
      (fluorescence) light. An optical multichannel analyzer system was used to record
      fluorescence spectra of the sites of interest. RESULTS: We analyzed the
      fluorescence spectra of 114 bladder areas (1 carcinoma in situ as well as 28
      malignant, 35 inflammatory, 7 dysplastic, 1 squamous metaplastic and 42 normal
      areas). These lesions included 44 difficult to diagnose suspicious tumors (11
      malignant and 33 nonmalignant). We developed an algorithm that used the I385:I455
      nm. fluorescence ratio to distinguish malignant from nonmalignant lesions,
      including inflammatory areas. By analyzing the data on all 114 lesions, we noted
      the sensitivity, specificity, and positive and negative predictive values of this
      method for differentiating malignant from nonmalignant bladder lesions to be 97,
      98, 93 and 99%, respectively. CONCLUSIONS: Under excitation with 337 nm. light a
      clear differentiation between malignant and nonmalignant bladder tissues can be
      made using the I385:I455 nm. autofluorescence ratio.

PMID- 8863547
TI  - Low dose Pasteur bacillus Calmette-Guerin regimen in stage T1, grade 3 bladder
      cancer therapy.
AB  - PURPOSE: We assessed the effectiveness of intravesical bacillus Calmette-Guerin
      (BCG) for high risk transitional cell carcinoma of the bladder. MATERIALS AND
      METHODS: A total of 51 patients with stage T1, grade 3 disease was treated with
      weekly instillations of 75 mg. Pasteur strain BCG for 6 weeks after transurethral
      resection for bladder cancer. An additional induction course was given to
      patients with relapse. Tumor-free patients followed a maintenance course with
      monthly instillations for 12 months. RESULTS: After the initial induction course
      37 of 51 patients (72.5%) remained tumor-free. A second induction course was
      necessary in 13 patients. After 1 or 2 induction courses 44 of 51 patients
      (86.3%) were tumor-free. The maintenance course was administered to 44 patients,
      with 41 remaining tumor-free. After a median followup of 33 months (range 3 to
      63) 28 patients (54.9%) were disease-free, 12 (23.5%) had recurrent tumors and 7
      (13.7%) had progression. The risk of treatment failure was significantly greater
      for solid than papillary tumors (p = 0.0006), recurrent than primary tumors (p =
      0.0052) and coexisting carcinoma in situ (p = 0.124) in multivariate analysis,
      and for early recurrence (p = 0.0001) in univariate analysis only. The drug was
      well tolerated with few side effects. CONCLUSIONS: Our data suggest that this low
      dose Pasteur BCG regimen is effective in the treatment of high risk superficial
      bladder cancer. Some tumor characteristics, such as solid appearance, coexisting
      carcinoma in situ, history of superficial transitional cell carcinoma and early
      relapse after the initial induction course, seem to be negative prognostic
      factors.

PMID- 8863549
TI  - Bladder cancer.

PMID- 8863548
TI  - Paclitaxel in advanced urothelial carcinoma: its role in patients with renal
      insufficiency and as salvage therapy.
AB  - PURPOSE: We evaluated the role of paclitaxel in patients with advanced urothelial
      carcinoma and renal insufficiency or as second line therapy for metastatic
      disease. MATERIALS AND METHODS: Nine patients with advanced urothelial carcinoma
      received 175 to 250 mg./m2. paclitaxel intravenously as a 24-hour infusion. Six
      patients had renal insufficiency with a median serum creatinine of 2.25 mg./dl.
      (range 1.9 to 3.2) and 3 with normal renal function were treated after disease
      progression following 1 to 2 prior chemotherapy regimens. RESULTS: Of 9 patients
      5 (56%) achieved a partial response, including 4 of 6 with renal insufficiency.
      Toxicity was primarily hematological with 4 patients experiencing febrile
      neutropenia. There was no adverse impact on renal function. CONCLUSIONS:
      Paclitaxel as a single agent represents an effective therapeutic alternative for
      patients with advanced transitional cell carcinoma of the urothelium and renal
      insufficiency precluding cisplatin or gallium nitrate based chemotherapy.
      Additionally, paclitaxel appears to be effective in patients in whom prior
      cisplatin based therapy failed.

PMID- 8863550
TI  - Long-term results of internal urethrotomy.
AB  - PURPOSE: A retrospective analysis was done of long-term results of internal
      urethrotomy to evaluate risk factors of stricture recurrence. MATERIALS AND
      METHODS: Followup studies were performed of 937 patients with urethral strictures
      treated with internal urethrotomy. Of the patients 357 were treated at Mainz
      University between 1977 and 1989 (mean followup 4.6 years) and 580 were treated
      at Bonn University between 1974 and 1986 (mean followup 3.2 years). RESULTS:
      Strictures recurred in 96 of 357 (26.9%) and 260 of 580 (44.8%) patients,
      respectively. Risk factors for recurrence were etiology (post-transurethral
      resection and inflammation), stricture longer than 1 cm. and postoperative
      catheter drainage for longer than 3 days. CONCLUSIONS: Urethroplasty should be
      considered in patients at high risk for stricture recurrence and with more than 1
      treatment failure after urethrotomy.

PMID- 8863551
TI  - Urethral recurrence in patients with orthotopic ileal neobladders.
AB  - PURPOSE: We identified the risk of urethral recurrence following cystectomy for
      transitions cell bladder carcinoma, stratified by pathological characteristics of
      the bladder tumor and type of urinary diversion. MATERIALS AND METHODS: The
      pathological characteristics and clinical courses of 174 men with a Kock ileal
      neobladder and 262 with a cutaneous urinary diversion were analyzed for time to
      urethral recurrence. RESULTS: Urethral recurrence was identified in 34 patients
      at a median of 1.6 years after cystectomy, for an overall 7.9% 5-year risk of
      recurrence. Carcinoma in situ (p = 0.71) and multifocality (p = 0.17) did not
      independently confer an increased risk of recurrence. Prostatic urethral
      involvement, particularly stromal invasion, significantly increased the
      probability of recurrence (p < 0.001). Patients with a Kock ileal neobladder had
      a significantly lower probability of recurrence compared to those with cutaneous
      diversion (p = 0.015), even when associated with prostatic urethral involvement.
      CONCLUSIONS: Patients with a Kock ileal neobladder have a lower risk of urethral
      recurrence than those with cutaneous urinary diversion, even when associated with
      a high risk pathological condition predicting increased risk of urethral
      recurrence.

PMID- 8863552
TI  - Expanded indications for the pubovaginal sling: treatment of type 2 or 3 stress
      incontinence.
AB  - PURPOSE: The usefulness of the pubovaginal sling procedure as primary treatment
      of stress incontinence associated with urethral hypermobility (type 2) or
      intrinsic sphincter deficiency (type 3) was determined. MATERIALS AND METHODS: A
      total of 60 consecutive cases of type 2 or 3 stress urinary incontinence was
      treated with a pubovaginal sling by 1 surgeon using a previously reported
      technique. Fluoroscopic urodynamic studies with leak point pressures were used to
      classify the type of incontinence. Of the 60 women 38 (63%) were diagnosed with
      type 2 and 22 (37%) with type 3 stress urinary incontience. Of these patients 24
      had previously undergone 1 or more anti-incontinence procedures. RESULTS: At a
      mean followup of 25 months 57 of the 60 patients (95%) were completely continent.
      In addition, 69% of patients with urgency had resolution of the urgency symptoms
      following the sling procedure. Transient postoperative urinary retention (median
      duration 6.5 days) was present in 60% of the patients. However, all women
      subsequently voided spontaneously without requiring further intermittent or Foley
      catheterization. Other complications occurred infrequently, and included urinary
      tract infection (13% of cases), de novo urgency (12%) and persistent incisional
      pain (5%). CONCLUSIONS: These early results suggest that the pubovaginal sling is
      a safe and effective treatment for primary or recurrent type 2 or 3 stress
      incontinence. The most worrisome complication, urinary retention, occurred
      temporarily in more than half of the patients but eventually resolved in all
      cases, usually within 10 days.

PMID- 8863553
TI  - A new vaginal procedure for cystocele repair and treatment of stress urinary
      incontinence.
AB  - PURPOSE: Treatment of cystoceles and stress urinary incontinence continues to
      evolve. We evaluated the efficacy of a new vaginal wall sling procedure for
      cystocele repair and treatment of stress urinary incontinence. MATERIALS AND
      METHODS: We present our experience with the vaginal wall sling procedure in 36
      patients (mean age 67.4 years) with cystocele. Of the patients 16 had undergone a
      prior pelvic operation. With our technique a vaginal wall tube was created with
      the base in the bladder neck and fixation to the periurethral tissues or
      suspension to the suprapubic area. RESULTS: Success rates were 95 and 82% for
      cystocele and stress incontinence repair, respectively. Mean followup was 17
      months. Morbidity was minimal and mean hospitalization was less than 5 days.
      CONCLUSIONS: This original, simple, noninvasive treatment is applicable for all
      cystoceles regardless of patient age or sexual activity, and has shown
      encouraging results. Based on our experience we recommend this procedure for
      repair of cystoceles and stress urinary incontinence.

PMID- 8863554
TI  - Female stress incontinence in the 1990s--changing concepts.

PMID- 8863555
TI  - A positive pharmacological erection test does not rule out arteriogenic erectile
      dysfunction.
AB  - PURPOSE: We tested the assumption that a positive pharmacological erection test
      implies normal penile vascular status. MATERIALS AND METHODS: From March 1991 to
      February 1995, 372 patients with erectile dysfunction were referred to our
      institutions. Penile hemodynamics were studied in 205 patients with color coded
      Doppler ultrasonography after intracavernous injection of 40 micrograms.
      prostaglandin E1. RESULTS: Of the 205 patients undergoing color coded Doppler
      utrasonography 92 had a rigid erection, that is a positive pharmacological
      erection test. Doppler wave analysis showed that 76 of the 92 patients (82%) had
      normal and 7 (8%) had borderline arterial function (peak systolic velocity
      greater than 35 and 25 to 35 cm. per second, respectively), while 9 (10%) had
      arterial insufficiency (peak systolic velocity less than 25 cm. per second). All
      92 patients had a normal veno-occlusive mechanism (resistance index greater than
      0.90). Of the 9 patients with pure arteriogenic erectile dysfunction 8 had risk
      factors for arterial insufficiency, such as aortoiliac occlusive disease (5),
      diabetes mellitus (3), longer than 20-year smoking history (8) and hypertension
      (7). CONCLUSIONS: Our study shows hemodynamically that a positive pharmacological
      erection test does not rule out arteriogenic erectile dysfunction.

PMID- 8863556
TI  - The efficacy of fluoxetine in the treatment of premature ejaculation: a double
      blind placebo controlled study.
AB  - PURPOSE: The efficacy of the selective serotonin re-uptake inhibitor fluoxetine
      in the treatment of premature ejaculation was examined. MATERIALS AND METHODS:
      The study comprised 17 patients with premature ejaculation who presented to the
      urology clinic of our medical school. In this double-blind study the patients
      were randomized into treatment groups receiving 20 mg. fluoxetine daily for 1
      week and 40 mg. daily afterward (group 1) or 1 capsule placebo daily for 1 week
      and 2 capsules daily afterward (group 2). The groups were evaluated according to
      the latent period of intravaginal ejaculation. RESULTS: The latent period of
      intravaginal ejaculation in group 1 was significantly longer than that in group
      2. Nausea, headache and insomnia were reported side effects. CONCLUSIONS:
      Fluoxetine may be regarded as a safe and effective alternative in the treatment
      of premature ejaculation.

PMID- 8863557
TI  - AMS 3-piece inflatable penile prosthesis implantation in men with Peyronie's
      disease: comparison of CX and Ultrex cylinders.
AB  - PURPOSE: We compared the ability of the CX and Ultrex cylinders to straighten the
      penis in men who received a 3-piece AMS 700 series inflatable penile prosthesis
      for erectile dysfunction and erectile deformity due to Peyronie's disease.
      MATERIALS AND METHODS: The records of 34 and 38 patients receiving devices CX and
      Ultrex cylinders, respectively, were reviewed. RESULTS: All 34 patients receiving
      the CX cylinders achieved complete penile straightening with cylinder inflation
      and bending alone. In 10 of 38 patients receiving the Ultrex cylinders complete
      straightening with cylinder inflation and bending could not be achieved, and
      simultaneous corporoplasty was necessary. CONCLUSIONS: Girth expanding CX
      cylinders have better penile straightening properties than girth and length
      expanding Ultrex cylinders. We recommend use of CX cylinders for 3-piece AMS 700
      series inflatable penile prosthesis implantation in men with Peyronie's disease.

PMID- 8863558
TI  - Male sexual dysfunction--pitfalls, pills and prostheses.

PMID- 8863559
TI  - Prognostic factors in carcinoma of the penis: multivariate analysis of 145
      patients treated with amputation and lymphadenectomy.
AB  - PURPOSE: The major issue in penile cancer is deciding who should or should not
      undergo lymph node dissection. Clinical and invasive methods are not reliable for
      staging. Clinical and pathological factors involved in lymph node metastases and
      prognosis were evaluated in 145 patients with penile carcinoma staged according
      to the 1978 TNM system, and treated with amputation and lymphadenectomy.
      MATERIALS AND METHODS: Clinical factors studied were patient age, race, disease
      evolution time, symptoms, and clinical T and N stages. Pathological factors of
      the primary tumor considered were tumor thickness, histological grade, lymphatic
      and venous embolization, infiltration of the corpora cavernosa, corpus spongiosum
      and urethra, mononuclear and eosinophilic infiltrates, and cell alterations
      suggestive of human papillomavirus. All slides were reviewed by 1 pathologist.
      The Cox regression hazards method for multifactorial analysis was used. RESULTS:
      Followup ranged from 0.7 to 453.2 months (mean 85.8, median 32.7). The 5-year
      disease-free and overall survival rates were 45.3 and 54.3%, respectively. Venous
      and lymphatic embolizations were the main factors affecting significantly the
      incidence of lymph node metastasis, which were the main risks factors for
      recurrence and death. Pathologically proved infiltration of the corpora
      cavernosa, urethra and adjacent structures, which corresponded to stages T2, T3
      and T4 disease, respectively, of the current TNM classification, were not
      significant predictors for incidence of lymph node metastasis, disease-free and
      overall survival or risk factors for recurrence and death. CONCLUSIONS: Because
      venous and lymphatic embolizations were related to greatest risk of lymph node
      metastasis, we propose their evaluation in staging and therapeutic planning of
      patients with infiltrative tumors of the penis.

PMID- 8863560
TI  - Testicular trauma: potential impact on reproductive function.
AB  - PURPOSE: The long-term effects of testicular trauma on reproductive function are
      unknown. In an effort to define the relationship between testicular injury and
      fertility in humans, we identified patients with a history of testicular trauma
      and assessed parameters commonly associated with fertility. MATERIALS AND
      METHODS: We reviewed 15 patients 23 to 59 years old who underwent immediate
      exploration after testicular trauma between 1972 and 1991. Of the patients 11
      were contacted and 8 returned for prospective followup. Reproductive and sexual
      histories, physical examination, measurements of serum hormones and antisperm
      antibodies, semen analysis and scrotal ultrasound were done. RESULTS: Of the 8
      patients 1 (13%) achieved and 7 (87%) did not attempt conception. Hormonal status
      was normal in all 8 patients. Six men had objective evidence of subfertility by
      semen analysis only, although none had severe oligospermia or asthenospermia and
      only 1 had severe teratospermia. Five of 9 traumatized testes were atrophic.
      Interestingly, only 1 patient had antisperm antibodies, the levels of which were
      probably low enough to be clinically insignificant. CONCLUSIONS: There was
      definite evidence of subfertility as assessed by abnormal semen analyses and
      atrophic testes following testicular trauma. However, the subfertility did not
      appear to be immune mediated nor did the patients present with infertility. Since
      only 1 patient had severely compromised fertility according to semen analysis we
      conclude that early repair can help preserve hormonal function as well as
      fertility.

PMID- 8863561
TI  - Percutaneous testis biopsy: an alternative to open testicular biopsy in the
      evaluation of the subfertile man.
AB  - PURPOSE: We evaluated the safety and efficacy of percutaneous testis biopsy by
      comparing the ultrasound appearance and histological status of testicular
      parenchyma obtained to those noted after open testis biopsy. MATERIALS AND
      METHODS: A total of 51 consecutive infertile men with azoospermia or severely
      impaired semen quality, in whom ductal obstruction was suspected, underwent
      percutaneous (31) or open (20) testis biopsy, with 58 and 34 procedures
      performed, respectively. Scrotal ultrasound was performed preoperatively, and at
      2 weeks and 1, 3 and 6 months after biopsy. In addition, immunoglobulins G and A
      antisperm antibody assays were obtained preoperatively and postoperatively. Two
      biopsy specimens were obtained from each testis for formal histological
      evaluation. A touch preparation was also performed and examined immediately for
      mature spermatozoa using phase contrast microscopy. RESULTS: All biopsies yielded
      adequate tissue for diagnosis and morphometric analysis. Of 58 percutaneous
      biopsies 4 (7%) demonstrated sonographic evidence of intratesticular bleeding,
      characterized by a hypoechoic region within the testicular parenchyma, which
      resolved by 6 months postoperatively. In contrast, 10 of 34 open biopsies (29%)
      showed evidence of intratesticular bleeding or a new area of increased
      echogenicity at 1 month after the procedure (intraparenchymatous scar). All
      intraparenchymatous scars persisted to 6 months postoperatively. No patient
      undergoing percutaneous or open testis biopsy had antisperm antibodies in the
      seminal fluid or serum (azoospermia cases) or on sperm postoperatively. Of the 32
      and 20 patients undergoing percutaneous and open testis biopsy 3 (9%) and 14
      (70%), respectively, required narcotic analgesia. All patients returned to
      routine activities within 24 hours after percutaneous testis biopsy. No
      postoperative infections or extratesticular hematomas were noted. Pathological
      study was diagnostic in all specimens. CONCLUSIONS: Percutaneous testis biopsy is
      well tolerated by the patient, with fewer apparent complications than and
      diagnostic value equal to open testis biopsy. Percutaneous testis biopsy should
      be considered an alternative to open biopsy.

PMID- 8863562
TI  - Infrared thermometry for rapid, noninvasive detection of reflux of spermatic vein
      in varicocele.
AB  - PURPOSE: We evaluated infrared thermometry for measurement of reflux of blood via
      the internal spermatic vein. MATERIALS AND METHODS: The change in scrotal
      temperature in patients with varicoceles and controls with different positions
      was measured with an infrared thermometer. RESULTS: Scrotal neck temperature in
      the patients increased during Valsalva's maneuver with upright position (mean
      plus or minus standard deviation 34.62 +/- 1.20 to 36.05 +/- 1.42C), while no
      statistically significant increase occurred in the controls (32.91 +/- 0.92 to
      33.42 +/- 1.15C). Two weeks after high ligation of the internal spermatic vein
      the scrotal temperature in the patients decreased to the same level (0.59 +/-
      0.84C) as in the controls. Using this method 2 subclinical varicoceles were also
      found on the right side in patients with a left varicocele. CONCLUSIONS: Infrared
      thermometry is noninvasive, rapid and simple for documenting varicoceles,
      including subclinical disease.

PMID- 8863563
TI  - Clinical studies of male infertility.

PMID- 8863564
TI  - Nerve sparing post-chemotherapy retroperitoneal lymph node dissection for
      advanced testicular cancer.
AB  - PURPOSE: Nerve sparing techniques are used routinely during retroperitoneal lymph
      node dissection in patients with low stage testis cancer in an attempt to
      preserve postoperative ejaculation. Preservation of ejaculation without an
      increased retroperitoneal recurrence rate in such patients prompted us to
      reevaluate the role of nerve sparing techniques in select patients undergoing
      post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS:
      Of 472 patients who underwent post-chemotherapy retroperitoneal lymph node
      dissection between March 1988 and January 1995, 93 (19.7%) underwent a nerve
      sparing procedure. Two patients died of disseminated cancer within 6 months after
      post-chemotherapy retroperitoneal lymph node dissection. In 10 patients the
      ejaculatory status could not be established from the clinical notes and the
      patient was lost to followup. The remaining 81 patients form the basis of this
      report. Disease status, complications and ejaculatory status were evaluated. Mean
      followup was 35.5 months. RESULTS: Of the patients 76.5% reported normal
      ejaculation after post-chemotherapy retroperitoneal lymph node dissection. Testis
      cancer recurred after nerve sparing surgery in 6 patients but no tumor was
      retroperitoneal. Ten pregnancies have been reported to date with uneventful term
      deliveries in 7. CONCLUSIONS: Select patients are candidates for nerve sparing
      post-chemotherapy retroperitoneal lymph node dissection. Although indications for
      nerve sparing techniques in the post-chemotherapy population have expanded, the
      local recurrence rate has not increased. Nerve sparing post-chemotherapy
      retroperitoneal lymph node dissection can preserve the inherent fertility
      potential of the patient without increasing retroperitoneal relapse rates.

PMID- 8863565
TI  - Nerve block in prostate surgery.
AB  - PURPOSE: We describe a novel technique for anesthetizing the prostate, which
      should be used for patients at risk undergoing prostate surgery with general,
      spinal or epidural anesthesia. MATERIALS AND METHODS: Local anesthesia to the
      prostatic plexus supplemented by monitored anesthesia care was performed on 40
      patients with outflow obstruction secondary to an enlarged prostate. Of the
      patients 34 underwent transurethral resection of the prostate, 5 underwent visual
      laser ablation and 1 underwent transurethral electrovaporization. A 20 gauge
      spinal needle was inserted via a suprapubic approach toward the base and apex of
      the prostate, and guided by the left index finger inserted into the rectum.
      Lidocaine was injected into the prerectal space. Bulging of the rectal wall
      caused by the amount of lidocaine injected was appreciated. Insertion into the
      proper area was essential for a good anesthetic result. RESULTS: Adequate
      anesthesia levels could be obtained without major complications. All but 1
      patient with poor bladder compliance were rendered free of a Foley catheter.
      There were no deaths. CONCLUSIONS: This technique has definite advantages for
      patients who are at risk for prostate surgery with general or spinal anesthesia.

PMID- 8863566
TI  - Age related urodynamic changes in patients with benign prostatic hyperplasia.
AB  - PURPOSE: We determined age related urodynamic changes in patients with untreated
      symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of
      222 patients (mean age 67.3 years, range 45 to 90) with the clinical diagnosis of
      symptomatic BPH was entered into a prospective protocol evaluating the
      international prostate symptom score (I-PSS), prostate volume, noninvasive
      uroflowmetry, residual volume and a pressure-flow study. To obtain a homogeneous
      study population only patients with a noninvasive maximum flow rate of 15 ml. per
      second or less and an I-PSS of 7 or more were eligible. RESULTS: There was no
      correlation between age and I-PSS (p > 0.05) but there was a statistically
      significant decrease in maximum flow rate (p = 0.045) and voided volume (p =
      0.0013) with age. Prostate volume increased constantly from 31.3 to 64.4 ml. in
      patients 45 to 50 and older than 80 years, respectively (p < 0.0001). Pressure
      flow studies revealed an age related decrease in cystometric bladder capacity (p
      = 0.0003) and invasive maximum flow rate (p = 0.0057) but no changes in detrusor
      pressure at maximum flow rate (p > 0.05), maximum detrusor pressure (p > 0.05)
      and linear passive urethral resistance relation (p > 0.05). The incidence of
      urodynamically proved bladder instability increased from 20 to 47% in men 45 to
      50 and older than 80 years, respectively. CONCLUSIONS: The well established age
      related decrease in maximum flow rate and voided volume in patients with
      prostatism cannot be attributed to an increase in bladder outflow obstruction or
      impaired detrusor function. Because 60% of all men older than 80 years did not
      have urodynamic obstruction despite a decreased maximum flow rate of 10 to 15 ml.
      per second, all patients meeting these criteria and having symptoms bothersome
      enough to justify surgery should undergo pressure-flow studies before surgical
      intervention.

PMID- 8863567
TI  - Significant correlation of the American Urological Association symptom score and
      a novel urodynamic parameter: detrusor contraction duration.
AB  - PURPOSE: Various investigators have reported the lack of specificity of the
      American Urological Association (AUA) symptom score and its poor correlation with
      urodynamic parameters. A retrospective study was performed to ascertain the
      correlation of the AUA symptom score with various urodynamic parameters,
      including detrusor contraction duration. MATERIALS AND METHODS: The urodynamic
      records of 120 consecutive patients with moderate (scores 8 to 19) or severe
      (scores greater than 19) symptoms were retrospectively analyzed to ascertain if
      the AUA symptom score correlated with the urodynamic parameters of maximum
      detrusor pressure, detrusor pressure at maximum flow, compliance, involuntary
      detrusor contractions and, a novel parameter, detrusor contraction duration.
      RESULTS: There were 63 men (mean age 59.7 years) and 57 women (mean age 58.8
      years). Mean AUA symptom score plus or minus standard deviation was 17.8 +/- 3.7
      and 15.4 +/- 2.9, respectively. There was no correlation between any urodynamic
      parameter and symptoms in women. In men increasing symptoms were associated with
      worsening urodynamic parameters. The 2 parameters that had the greatest
      correlation with symptom severity were incidence of involuntary detrusor
      contractions (r = 0.56, p < 0.006) and detrusor contraction duration (r = 0.61, p
      < 0.003). Furthermore, increasing incidence of involuntary detrusor contractions
      was associated with increasing irritative symptoms, while increasing detrusor
      contraction duration was correlated with increasing obstructive symptoms.
      Detrusor contraction duration was correlated with symptom severity and urodynamic
      outlet obstruction in men. CONCLUSIONS: These data demonstrated that the AUA
      symptom score correlates with certain urodynamic parameters. Furthermore, this
      correlation occurs in men in contrast to women despite similar AUA symptom
      scores. In addition, increasing detrusor contraction duration is associated with
      worsening symptoms and may herald worsening obstruction. Further prospective
      studies are underway to determine the prognostic value of these urodynamic
      parameters in altering ultimate outcomes of treatment.

PMID- 8863568
TI  - A statistical study of the American Urological Association symptom index for
      benign prostatic hyperplasia in participants of mass screening program for
      prostatic diseases using transrectal sonography.
AB  - PURPOSE: A study was done on the prevalence of urinary symptoms in community
      based populations in Japan regarding the influences of aging and benign prostatic
      hyperplasia (BPH) as evaluated by transrectal sonography. MATERIALS AND METHODS:
      In 961 Japanese men 55 to 87 years old who underwent mass screening for prostatic
      diseases the American Urological Association symptom index scores were compared
      with age and ultrasonic diagnosis of the prostate. RESULTS: Moderate to severe
      symptoms (symptom score 8 or more) were found in 265 of our 961 samples (27.6%),
      while BPH was also recognized ultrasonically in 197 (20.5%). Frequencies of
      urinary symptoms and BPH increased significantly with age. BPH related increase
      in total symptom scores occurred only in select men when adjusted by age.
      CONCLUSIONS: The ability of the American Urological Association symptom index to
      characterize BPH in an individual was limited because of the lack of specificity
      to the disease along with the considerable influence of aging on the symptom
      score. Currently, transrectal sonography is the most reliable method for the
      definitive diagnosis of BPH.

PMID- 8863569
TI  - Immunohistochemical localization of metallothionein in human prostate cancer.
AB  - PURPOSE: We investigated the expression of metallothionein in human prostate
      cancer. MATERIALS AND METHODS: Formalin fixed and paraffin embedded tissue
      specimens from 45 patients with primary prostate cancer were stained for
      metallothionein using a standard immunohistochemical technique. RESULTS:
      Metallothionein was detected in 15 of 45 prostate cancers (33.3%). Cytoplasmic
      and nuclear staining occurred in most cells. Additionally, metallothionein was
      found in basement membrane surrounding the cancer cells in 2 cases with
      metallothionein expression, and in secretory products of the lumen in a few
      cases. Statistical analysis for metallothionein expression related to tumor grade
      revealed a significant difference between high (7 to 10) and low (2 to 4) Gleason
      scores (p < 0.001), as well as between middle (5 and 6) and low scores (p <
      0.05). However, no relationship was found with clinical stage. CONCLUSIONS: Our
      data suggest a close correlation of metallothionein expression with tumor grade
      and a wide range of metallothionein expression in prostate cancer.

PMID- 8863570
TI  - Effect of extracorporeal shock wave lithotripsy on prostate specific antigen.
AB  - PURPOSE: We evaluated the effects of extracorporeal shock wave lithotripsy (ESWL)
      of distal ureteral calculi on serum prostate specific antigen (PSA). MATERIALS
      AND METHODS: A total of 29 consecutive men with distal ureteral calculi at a
      maximum of 25 mm. from the ureteral orifice, and without any history of urinary
      tract infection, benign prostatio hyperplasia or prostate cancer underwent ESWL
      with the Dornier MPL 9000 X lithotriptor. The therapeutic focus size was 48 X 7
      mm. PSA was measured exactly 5 minutes before ESWL, as well as 120 minutes, 24
      hours and 7 days after termination of treatment. RESULTS: Fragmentation rate was
      100% and all patients were stone-free within 1 week of therapy. There was no
      statistically significant difference between PSA values before and after
      treatment. Only 15 patients had a slight increase in PSA at 120 minutes after
      treatment (range 0.01 to 0.41 ng./ml., mean 0.07). CONCLUSIONS: ESWL can be
      performed in men at risk for prostate cancer without impairing the predictive
      value of PSA.

PMID- 8863571
TI  - Prospective evaluation of prostate specific antigen and prostate specific antigen
      density in the detection of nonpalpable and stage T1C carcinoma of the prostate.
AB  - PURPOSE: We evaluated prospectively prostate specific antigen (PSA) and prostate
      specific antigen density in the detection of prostate cancer in patients with
      normal findings on digital rectal examination with and without normal transrectal
      ultrasound. MATERIALS AND METHODS: Consecutive patients (184) with an elevated
      serum PSA and normal digital rectal examination underwent transrectal ultrasound
      with lesion directed and systematic biopsies (6 if prostatic volume was 50 cc or
      less and 12 if volume was more than 50 cc). Receiver operating characteristic
      curves, predictive values and likelihood ratios were calculated for PSA and PSA
      density. RESULTS: Of the 184 patients 50 (27%) with a normal digital rectal
      examination had cancer compared to 30 of 112 (27%) with a normal digital rectal
      examination and transrectal ultrasound. Median PSA or PSA density did not differ
      between the positive and negative biopsy groups among patients with a normal
      digital rectal examination (8.4 versus 7.1 and 0.22 versus 0.14 ng./ml.,
      respectively) or a normal digital rectal examination and transrectal ultrasound
      (8.2 versus 7.5 and 0.21 versus 0.14 ng./ml., respectively). PSA density was
      superior to PSA by receiver operating characteristic analysis for cancer
      detection when all PSA values or those between 4 and 20 ng./ml. were considered.
      However, the significance was lost for a PSA of 4 to 10 ng./ml. Likelihood ratios
      demonstrated insignificant changes in the post-test probability if PSA density
      was used to determine the need for biopsy and many cancers would have been
      missed. CONCLUSIONS: PSA density should not be used to determine the need for
      biopsy in patients with a normal digital rectal examination and/or transrectal
      ultrasound.

PMID- 8863572
TI  - Urinary pyridinoline and deoxypyridinoline as potential markers of bone
      metastasis in patients with prostate cancer.
AB  - PURPOSE: The levels of probable markers of bony metastatic disease were measured
      to evaluate their efficacy as predictors of disease and therapeutic outcome.
      MATERIALS AND METHODS: Urinary pyridinoline, urinary deoxypyridinoline, serum
      alkaline phosphatase and serum osteocalcin were measured in patients with benign
      prostatic hyperplasia, clinically localized prostate cancer and prostate cancer
      with bone metastases. Also, urinary pyridinoline and deoxypyridinoline were
      compared in 2 groups of patients with metastatic prostate cancer of the bone who
      demonstrated progression or positive response to treatment. Urinary pyridinoline
      and deoxypyridinoline were determined by high performance liquid chromatography
      and were normalized to urinary creatinine. RESULTS: Levels of pyridinoline and
      deoxypyridinoline in urine, and the level of alkaline phosphatase in serum from
      patients with bone metastatic prostate cancer were significantly greater than
      levels in patients with benign prostatic hyperplasia or localized prostate
      cancer. Serum osteocalcin levels failed to separate the 3 groups. Serial
      measurement of urinary pyridinoline and deoxypyridinoline was correlated with a
      positive response to treatment (decreased) and with clinical progression of
      disease (increased) before detection of new bone lesions by bone scintigraphy.
      CONCLUSIONS: Measurement of urinary pyridinoline and deoxypyridinoline may
      provide a useful marker of prostate cancer metastatic to bone and may be useful
      in monitoring the response to treatment.

PMID- 8863573
TI  - Marriage and mortality in prostate cancer.
AB  - PURPOSE: We evaluated the association of marital status and survival in patients
      with prostate cancer. MATERIALS AND METHODS: Using the 146,979 prostate cancer
      patients of the 1973 to 1990 public use tape of the Surveillance, Epidemiology
      and End Results program we performed survival analysis and multivariate
      proportional hazards modeling to estimate the relative risk of mortality.
      RESULTS: Married patients had significantly longer median survival than those who
      were divorced, single, separated or widowed. In models that controlled for age,
      stage, race and treatment, married patients had a significantly lower risk of
      mortality than those who were divorced, single, separated or widowed.
      CONCLUSIONS: Several hypothetical models can explain the association of marital
      status and mortality in men with prostate cancer. The most attractive model
      relies on the putative salutary effects of being married on social support and/or
      mood. A social support and depressed mood model of mortality raises the
      possibility that in prostate cancer quality of life determines quantity of life.
      Understanding the relationships among marital status, social support, mood and
      mortality could open the way to rational strategies for postponing death in men
      with prostate cancer.

PMID- 8863574
TI  - Prostate cancer--bench to bedside.

PMID- 8863575
TI  - Early results with antegrade collagen injection for post-radical prostatectomy
      stress urinary incontinence.
AB  - PURPOSE: Results of retrograde transurethral collagen injection for treatment of
      stress urinary incontinence have been generally disappointing for men with
      intrinsic sphincter deficiency following radical prostatectomy. We describe a new
      technique of antegrade transvesical collagen injection using suprapublic
      percutaneous bladder access. MATERIALS AND METHODS: Between October 1994 and
      January 1996, 20 patients underwent antegrade collagen injection for post-radical
      prostatectomy stress urinary incontinence. Evaluation by pad test, urodynamics
      and subjective scores was performed before and after injection. RESULTS: At a
      mean followup of 8.5 months 9 of 20 patients (45%) had significant subjective
      improvement and 5 (25%) were totally dry. CONCLUSIONS: Antegrade collagen
      injection is a promising and simple method of correcting post-radical
      prostatectomy stress urinary incontinence. Further study and longer followup are
      necessary to determine its precise role in the treatment of this condition.

PMID- 8863576
TI  - Risk factors for urinary incontinence after radical prostatectomy.
AB  - PURPOSE: We identified risk factors associated with urinary incontinence after
      radical retropubic prostatectomy. MATERIALS AND METHODS: The time from operation
      until urinary continence was achieved was determined by chart review and
      questionnaire in 581 patients who were continent before undergoing radical
      retropubic prostatectomy between 1983 and 1994. Using univariate and multivariate
      analyses of data gathered prospectively, we examined risk factors associated with
      incontinence in these patients. RESULTS: The actuarial rate of urinary continence
      at 24 months was 91% for the entire patient population and 95% for those treated
      after 1990. Many factors were associated with the risk of incontinence in
      univariate Cox proportional hazards regression analysis (patient age and weight,
      degree of obstructive voiding symptoms, prior transurethral resection of the
      prostate, clinical stage, intraoperative blood loss, resection of neurovascular
      bundles, postoperative anastomotic stricture and technique of vesicourethral
      anastomosis). However, in a multivariate analysis the factors that were
      independently associated with increased chance of regaining continence were
      decreasing age, a modification in the technique of anastomosis (introduced in
      1990), preservation of both neurovascular bundles and absence of an anastomotic
      stricture. With introduction of the new surgical technique in 1990 the median
      time to continence decreased from 5.6 to 1.5 months and the rate of continence at
      24 months increased from 82 to 95%. CONCLUSIONS: While the risk of urinary
      incontinence after radical prostatectomy is related to the uncontrollable factor
      of patient age, it is also sensitive to the surgical technique used.

PMID- 8863577
TI  - Co-morbidities and survival of men with localized prostate cancer treated with
      surgery or radiation therapy.
AB  - PURPOSE: We determined the impact of preexisting co-morbidities on survival of
      men with clinical stages T1b and T2NXM0 prostate cancer treated with surgery or
      radiation therapy. MATERIALS AND METHODS: A weighted co-morbidity score was
      determined for 276 consecutive men treated with surgery (138) or radiation
      therapy (138) at a Veterans Affairs medical center and was correlated with
      actuarial freedom from death due to co-morbid disease. RESULTS: After a median
      potential followup of 7.0 years 91 patients (33%) died of co-morbid disease and
      20 (7%) died of cancer related causes. There were highly significant correlations
      between actuarial survival and weighted co-morbidity (p < 0.000001), and the 10
      year actuarial survivals in men with no or severe co-morbidities were 66 and 9%,
      respectively. Associations between patient age and co-morbidity score were highly
      significant (p < 0.0001). The age adjusted risk of co-morbid death was 5.7 times
      greater in men with severe compared to no co-morbidities. There were also
      significant correlations between actuarial survival and weighted co-morbidity
      among patients treated with surgery (p = 0.02) and radiation therapy (p =
      0.0002). Patient age and severity of co-morbidities were significantly greater
      among men treated with radiation therapy compared to surgery, and age adjusted
      risk of co-morbid death among men with a co-morbidity score of 1 was 3.8 times
      greater among men treated with radiation therapy (p = 0.025). CONCLUSIONS: Cancer
      related deaths are unusual within 5 to 10 years after surgery or radiation
      therapy in men with stages T1b and 2 prostate cancer. The risk of death during
      this interval is directly related to the severity of co-morbid conditions, which
      should be factored in an individual when assessing the advisability of
      therapeutic intervention. Since patient co-morbidities impact all cause survival,
      quantitative assessment of co-morbidities using validated instruments offers a
      method to control partially for the variabilities of health status among men
      receiving different treatments for localized prostate cancer.

PMID- 8863579
TI  - Risk factors for urinary incontinence after radical prostatectomy.

PMID- 8863578
TI  - Radiotherapy for high grade clinically localized adenocarcinoma of the prostate.
AB  - PURPOSE: We defined the efficacy of radiotherapy for the treatment of high grade
      (Gleason scores 8 to 10) adenocarcinoma of the prostate. MATERIALS AND METHODS: A
      total of 50 patients underwent radiotherapy with curative intent for clinically
      localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities
      affiliated with the University of California San Francisco. Patients were
      considered to have biochemical failure if they had a significant increase in
      prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to
      greater than 1.0 ng./ml. or a positive biopsy. RESULTS: Among the 50 patients
      median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or
      T2 in 46% of the cases and stage T3 or T4 in 54%. The overall actuarial
      probability of freedom from biochemical failure at 4 years was 23%. In a
      multivariate analysis including all patients pretreatment PSA was the only
      predictor of PSA failure, with 64% free of progression if the pretreatment PSA
      was 10 ng./ml. or less compared to only 16% at 3 years if PSA was more than 10
      ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA
      less than 20 ng./ml. 83% of those treated to more than 71 Gy. were free of
      progression compared to 0% for those treated to less than 71 Gy. (p = 0.03). In a
      multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T
      stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy.
      (relative risk 4.0, p = 0.06) were associated with a favorable outcome.
      CONCLUSIONS: At 4 years the freedom from PSA failure following radiotherapy for
      high grade prostate cancer was comparable to previously reported surgical series.
      The high failure rate among patients with PSA greater than 20 ng./ml. suggests
      that these patients should be considered for investigational approaches. The
      apparent improvement in freedom from progression with the use of higher doses
      provides reason for optimism.

PMID- 8863580
TI  - The use of radiotherapy for patients with isolated elevation of serum prostate
      specific antigen following radical prostatectomy.
AB  - PURPOSE: An analysis was performed to assess the outcome of patients who received
      radiotherapy for isolated elevation of serum prostate specific antigen (PSA)
      levels following radical retropubic prostatectomy. MATERIALS AND METHODS: Forty
      six patients were initially treated for localized prostate cancer with radical
      retropubic prostatectomy following negative pelvic lymphadenectomy. These
      patients had detectable serum PSA 6 or more months postoperatively. No patient
      had other clinical evidence of recurrent disease as determined by history,
      physical examination, bone scan, computerized tomography of the abdomen and
      pelvis, chest radiographs, complete blood cell counts and serum chemistry
      profiles. The patients received prostate bed irradiation using 10 MV. x-rays and
      a 4-field approach. Doses ranged from 60.0 to 67.0 Gy. in 1.8 to 2.0 Gy.
      fractions. Freedom from failure after radiotherapy was defined as maintaining a
      PSA of 0.3 ng./ml. or less without hormonal intervention. RESULTS: In 27 of the
      46 patients (59%) PSA had decreased to 0.3 ng./ml. or less at last measurement
      without hormonal intervention. The freedom from failure rate was 50% at 3 and 5
      years. More favorable responses to salvage radiotherapy occurred in patients with
      low grade tumors and serum PSA 1.1 ng./ml. or less at initiation of radiotherapy.
      Patients, receiving radiation doses of 64 Gy. or more had more favorable response
      rates than those receiving lesser doses. CONCLUSIONS: Isolated elevations of
      serum PSA following prostatectomy reflect residual disease. Radiotherapy
      administered to the prostate bed effectively decreased serum PSA in approximately
      half of the cases. This effect appears to be accomplished by eradicating tumor
      cells in the prostate bed.

PMID- 8863581
TI  - The role of renal scintigraphy in the evaluation of spinal cord injury patients
      with presumed urosepsis.
AB  - PURPOSE: We attempted to differentiate pyelonephritis, defined as upper urinary
      tract parenchymal infection, from fever due to other sources in patients with
      spinal cord injury by radioisotope renal scintigraphy. MATERIALS AND METHODS: A
      total of 13 consecutive spinal cord injury patients 21 to 54 years old (level of
      injury C4 to cauda equina) was hospitalized with urosepsis. The diagnosis was
      based on medical history, physical examination and laboratory evaluation,
      including blood, urine, sputum and wound fluid culture and sensitivity, and a
      99mtechnetium glucoheptonate renal scan for pyelonephritis. Renal scan results
      were compared to 1 or more of several studies performed in each case, including
      ultrasonography, excretory urography and axial computerized tomography. RESULTS:
      Glucoheptonate renal scintigraphy accurately diagnosed pyelonephritis in all 7
      patients with a scintigraphic B lesion. In 2 patients with a C lesion on
      scintigraphy, representing a cortical scar, other sources of sepsis were
      identified. In the 4 patients with negative renal scans pyrexia was attributed to
      active decubitus wound infection and osteomyelitis. Positive and negative
      predictive values of renal scanning were each 100%. CONCLUSIONS: Nuclear medicine
      renal scanning is a valuable adjunct in the evaluation of sepsis and presumed
      urosepsis in the spinal cord injury population.

PMID- 8863582
TI  - Circumferential laser vaporization for severe meatal stenosis secondary to
      balanitis xerotica obliterans.
AB  - PURPOSE: A new technique for treating meatal stenosis due to balanitis xerotica
      obliterans was used. MATERIALS AND METHODS: Three patients with complete urinary
      retention and 1 with severe obstructive symptoms due to balanitis xerotica
      obliterans were treated with circumferential carbon dioxide laser vaporization of
      the urethral meatus. RESULTS: All 4 patients void spontaneously at 1 to 4.5
      months of followup with peak flow rates of 1.25 to more than 3.0 standard
      deviations less than the mean normal peak flow rates at similar voided volumes.
      All patients are pleased with the postoperative results. CONCLUSIONS:
      Circumferential carbon dioxide laser vaporization monotherapy shows promise in
      treatment of meatal stenosis associated with balanitis xerotica obliterans.

PMID- 8863583
TI  - Sex differences in the determination of abdominal leak point pressure in patients
      with intrinsic sphincter deficiency.
AB  - PURPOSE: We determined the effect of a urethral catheter on abdominal leak point
      pressure in men and women with intrinsic sphincter deficiency. MATERIALS AND
      METHODS: A total of 21 consecutive men treated with prostatectomy and 19 women
      with intrinsic sphincter deficiency underwent abdominal leak point pressure
      measurements with a rectal catheter before and after removal of a 10F urethral
      catheter. RESULTS: Of the 19 women 2 had leakage only when the urethral catheter
      was removed, while 17 had excellent correlation between abdominal leak point
      pressures before and after catheter removal (r = 0.83). In contrast, 10 of 21 men
      had leakage only when the urethral catheter was removed and 11 had weak
      correlation between abdominal leak point pressures before and after catheter
      removal (r = 0.46). CONCLUSIONS: An indwelling 10F urethral catheter is much more
      likely to invalidate abdominal leak point pressure measurement in men than in
      women with intrinsic sphincter deficiency.

PMID- 8863584
TI  - Urethral closure pressure changes with age in men.
AB  - PURPOSE: The natural history of external urethral sphincter function in elderly
      men is unknown. MATERIALS AND METHODS: In 257 men 45 to 88 years old external
      sphincter function changes with aging were analyzed by urodynamic studies,
      including functional urethral length, maximal urethral pressure, sphincter length
      and maximum urethral pressure during voluntary contraction. RESULTS: Mean
      functional urethral length was 51.9 mm. and there was no statistical decrease
      with age. However, sphincter length decreased with age from 24.3 to 14.8 mm.,
      maximal urethral pressure from 88.7 to 55 cm. water and maximal urethral pressure
      during voluntary contraction from 221.4 to 166.3 cm. water. CONCLUSIONS:
      Sphincter function according to urethral pressure profile decreases with patient
      age.

PMID- 8863585
TI  - Modified Ingelman-Sundberg bladder denervation procedure for intractable urge
      incontinence.
AB  - PURPOSE: We determined the efficacy of the modified Ingelman-Sundberg procedure
      in women with urge incontinence and intractable detrusor instability. MATERIALS
      AND METHODS: Women with urge incontinence and detrusor instability, in whom
      medical and behavioral therapy failed, received transvaginal local anesthesia to
      block the terminal pelvic nerve branches to the bladder. Urge incontinence
      resolved temporarily in 25 patients, who subsequently underwent modified Ingelman
      Sundberg transvaginal bladder denervation. All patients underwent preoperative
      urodynamic evaluation but documented detrusor instability was not a requirement
      for surgery. RESULTS: Of the patients 16 (64%) were cured of urge incontinence
      with substantial relief of detrusor instability, 2 (8%) had temporary improvement
      and 7 (28%) had no change. No patient who was cured required further surgery
      (mean followup 14.8 months, range 4 to 30). Use of anticholinergic agents also
      decreased dramatically: 5 patients used no, 9 used 1 and 2 used 2 medications.
      Detrusor instability was documented in 44% of the patients and was not predictive
      of operative outcome. There were no major complications of the procedure.
      Operative time was approximately 15 minutes. CONCLUSIONS: In patients with urge
      incontinence and medically refractory detrusor instability, with few simple
      choices for treatment, the modified Ingelman-Sundberg procedure is an excellent
      surgical option that yields good results with minimal morbidity.

PMID- 8863586
TI  - Acute cerebrovascular accident and lower urinary tract dysfunction: a prospective
      correlation of the site of brain injury with urodynamic findings.
AB  - PURPOSE: We evaluated the effects of an acute cerebrovascular accident on the
      lower urinary tract and correlated the site of cerebrovascular accident with
      findings on urodynamic study. MATERIALS AND METHODS: A total of 45 men and 15
      women underwent a complete urodynamic study with electromyography within 72 hours
      of a cerebrovascular accident. Patients were divided into 5 different groups
      based on urodynamic findings. RESULTS: The majority of cortical and internal
      capsule lesions resulted in detrusor hyperreflexia. A total of 28 patients (47%)
      had urinary retention, mainly due to detrusor areflexia (75%). Of 20 patients
      with hemorrhagic infarcts 17 (85%) had areflexia, compared to only 4 of 40 (10%)
      with ischemic infarcts. All 6 patients with cerebellar infarction had detrusor
      areflexia. CONCLUSIONS: Our results confirm many previously reported findings. In
      addition, there was a specific correlation of cerebellar and hemorrhagic
      infarctions with detrusor areflexia.

PMID- 8863587
TI  - Vesicourethral dysfunction--neurogenic and nonneurogenic considerations.

PMID- 8863588
TI  - Laparoscopic pyelolithotomy in an ectopic kidney.

PMID- 8863589
TI  - 2,8-Dihydroxyadenine stone formation in a renal transplant recipient due to
      adenine phosphoribosyltransferase deficiency.

PMID- 8863590
TI  - Splenic rupture after extracorporeal shock wave lithotripsy.

PMID- 8863591
TI  - Acute appendicitis presenting as a perinephric abscess.

PMID- 8863592
TI  - Renal cavernous hemangioma in a patient with the acquired immunodeficiency
      syndrome.

PMID- 8863593
TI  - Pregnancy after relief of ejaculatory duct obstruction by aspiration
      decompression of an ectopic ureter.

PMID- 8863594
TI  - Ureteral injury secondary to an inferior vena caval filter.

PMID- 8863595
TI  - Polyomavirus mimicking high grade transitional cell carcinoma.

PMID- 8863597
TI  - Tuberculous iliac lymphadenitis: a rare complication of intravesical bacillus
      Calmette-Guerin and cause of tumor over staging.

PMID- 8863596
TI  - Adenocarcinoma of the ampulla of Vater and head of the pancreas metastatic to the
      ureter: report of 2 cases.

PMID- 8863598
TI  - Management of urethral recurrence after radical cystectomy and neobladder
      creation by urethroscopic resection and fulguration.

PMID- 8863599
TI  - Corpus cavernosum-spongiosum fistula after blunt pelvic trauma: successful
      resolution with digoxin.

PMID- 8863600
TI  - A surgical approach to penoscrotal lymphedema.

PMID- 8863601
TI  - Testicular juvenile capillary hemangioma.

PMID- 8863602
TI  - Primary squamous cell carcinoma of the testis.

PMID- 8863603
TI  - Giant scrotal lipomatosis.

PMID- 8863604
TI  - Iodide mumps after intravenous and oral administration of contrast medium.

PMID- 8863605
TI  - Wear particles in bilateral internal iliac lymph nodes after loosening of a
      painless unilateral cemented total hip arthroplasty.

PMID- 8863606
TI  - Intravesical methylmethacrylate after revision hip arthroplasty.

PMID- 8863607
TI  - Practice trends of American urologists in the treatment of impotence,
      incontinence and infertility.
AB  - PURPOSE: Trends of urologist practice patterns in evaluating and treating
      impotence, incontinence and infertility in the United States were assessed.
      MATERIALS AND METHODS: In July 1995 the executive interviewing branch of the
      Gallup Organization selected randomly and interviewed by telephone 533 practicing
      urologists in the United States who had provided urological patient care for more
      than 20 hours per week, practiced in 1994 and completed a urological residency
      program. RESULTS: Treatment of male sexual dysfunction and female urinary
      incontinence comprises a significant portion of the professional activity of
      United States urologists. However, evaluation and management of male infertility
      occupy a small portion of the average urological work load. While more than half
      of United States urologist office clinical laboratories were inspected in 1994,
      only 2% failed evaluation due to major deficiencies. CONCLUSIONS: Male sexual
      dysfunction and female urinary incontinence are major areas of urological
      practice in the United States but male infertility is not. Few United States
      urologist clinical laboratories failed inspection because of major deficiencies.

PMID- 8863608
TI  - Re: Hereditary papillary renal cell carcinoma: clinical studies in 10 families.

PMID- 8863609
TI  - Re: Changing trends in the management of iatrogenic ureteral injuries.

PMID- 8863610
TI  - Re: Urological symptomatology in patients with reflex sympathetic dystrophy.

PMID- 8863611
TI  - Re: Laparoscopic laser assisted auto-augmentation of the pediatric neurogenic
      bladder: early experience with urodynamic followup.

PMID- 8863612
TI  - Re: The quality of life during intravesical bacillus Calmette-Guerin therapy.

PMID- 8863613
TI  - Re: Efficacy of prilocaine-lidocaine cream in the treatment of premature
      ejaculation.

PMID- 8863614
TI  - Re: Complications of penile lengthening and augmentation seen at 1 referral
      center.

PMID- 8863615
TI  - Re: Early and late long-term effects of vasectomy on serum testosterone,
      dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels.

PMID- 8863616
TI  - Re: Prostate cancer mortality in patients surviving more than 10 years after
      diagnosis.

PMID- 8863617
TI  - Enucleative surgery for stage I nephroblastoma with a normal contralateral
      kidney.
AB  - PURPOSE: Tumor enucleation is not recommended for children with nephroblastoma
      and a normal contralateral kidney. However, in adults with unilateral low stage
      renal cell carcinoma tumor enucleation may offer an alternative to radical
      nephrectomy, since functioning renal tissue is preserved without a greater risk
      of residual microscopic disease. Enucleative surgery may be more reasonable in
      children with nephroblastoma, because the risk of relapse can be reduced with
      chemotherapy. Therefore, we prospectively evaluated the feasibility of
      enucleative surgery in children with stage I unilateral nephroblastoma. MATERIALS
      AND METHODS: Between 1992 and 1995, 13 children with nephroblastoma and a normal
      contralateral kidney were consecutively admitted to our surgical unit. Possible
      candidates for tumor enucleation were evaluated according to certain criteria,
      including stage I disease at diagnosis, well-defined margins on post-contrast
      computerized tomography and at least 50% of the functioning kidney could be
      preserved. Preoperative and postoperative chemotherapy was given in all cases.
      RESULTS: Of 4 children with preservation of more than 50% of the functioning
      kidney 3 were considered eligible for enucleation. The tumors, which were
      confined to the mid kidney in 2 children and upper renal pole in 1, were
      successfully enucleated without hypothermia or vascular occlusion. All 3 children
      are disease-free at 49, 48 and 26 months of followup, respectively. Renal
      function has been almost completely restored postoperatively. CONCLUSIONS: These
      preliminary data suggest that enucleative surgery may be a reasonable option in
      select children with stage I nephroblastoma and a normal contralateral kidney.

PMID- 8863618
TI  - Outcome analysis of Mitrofanoff principle applications using appendix and ureter
      to umbilical and lower quadrant stomal sites.
AB  - PURPOSE: We compared the indications for and results of application of the
      Mitrofanoff principle using appendix and ureter to umbilical and lower quadrant
      stomal sites. MATERIAL AND METHODS: We created continent catheterizable conduits
      in 60 patients 3 days to 20 years old (mean age 8.8 years). The primary
      indication was refractory urinary incontinence associated with bladder or cloacal
      exstrophy, or anomalies in 31 cases. We constructed 38 umbilical (all appendix)
      and 22 lower quadrant (10 appendix and 12 ureter) stomas. Mean followup was 3
      years. RESULTS: We preferred the umbilicus as a stomal site for its cosmetic
      value. The most common indication for a lower quadrant stomal site was
      preservation of the retroperitoneal course of the ureter. The stomal stenosis
      rate was 13 and 4% in patients with umbilical and lower quadrant stomas,
      respectively. We preferred the appendix as a conduit due to availability.
      Indications for the ureter as a catheterizable conduit were absence of an
      adequate appendix or presence of a healthy ureter after nephrectomy. The
      appendiceal and ureteral conduits were catheterizable in 94 and 84% of patients,
      respectively, and continence was achieved in 97%. CONCLUSIONS: In a complex group
      of patients with incontinence application of the Mitrofanoff principle yielded
      good results for either combination of stomal site or catheterizable conduit.
      Appendicovesicostomy to the umbilicus remains our preferred procedure.

PMID- 8863619
TI  - Reconstructive options in genitourinary rhabdomyosarcoma.
AB  - PURPOSE: We attempted to develop a rational and consistent scheme for surgical
      reconstruction in patients with genitourinary rhabdomyosarcoma. MATERIALS AND
      METHODS: We reviewed the records of 35 patients with resectable genitourinary
      rhabdomyosarcoma treated from 1970 to 1993. RESULTS: Primary sites included
      bladder in 11 cases, prostate in 13, vagina/uterus in 9 and pelvic tumors of
      uncertain origin in 2. A total of 33 patients underwent surgery, including
      partial and radical cystectomy in 17 (bowel conduit diversion in 10, continent
      urinary diversion in 6 and ureterosigmoidostomy in 1). Overall 30 of the 33
      surgical patients are free of disease 4 months to 24 years after diagnosis.
      CONCLUSIONS: A nonrefluxing colon conduit is appropriate at cystectomy. Continent
      diversion fashioned from the original conduit may be planned as the patient
      achieves a durable disease-free status.

PMID- 8863620
TI  - Natural history of vesicoureteral reflux in siblings.
AB  - PURPOSE: We attempted to assess the natural course of vesicoureteral reflux after
      it was detected in asymptomatic siblings of children with reflux, and to
      determine predictors of and time to resolution. MATERIALS AND METHODS: We
      reviewed the records and radionuclide cystograms of 76 girls and 32 boys 2 weeks
      to 103 months old (mean age 21 months) with vesicoureteral reflux detected in a
      sibling screening program. Predictors were determined using logistic regression
      and survival analysis. RESULTS: Vesicoureteral reflux resolved in 52.8% of cases
      at a mean followup of 18.5 months. Yearly resolution rates exceeded 28%.
      Predictors of the likelihood of resolution were not identified. At diagnosis
      unilateral reflux and mild reflux were independent and univariate predictors,
      respectively, of more rapid resolution. CONCLUSIONS: By showing that spontaneous
      resolution is likely for children with vesicoureteral reflux detected in a
      sibling screening program, this study supports nonsurgical management with annual
      imaging evaluation.

PMID- 8863621
TI  - Screening for reflux--the current status.

PMID- 8863622
TI  - Four-hour voiding observation in healthy infants.
AB  - PURPOSE: We present the 4-hour voiding observation as a method for basic
      assessment of bladder function in infants and nontoilet trained children.
      MATERIALS AND METHODS: Voiding pattern, including number of voidings, voided
      volume, bladder capacity and residual urine for 4 hours, was determined
      noninvasively in 43 healthy infants. RESULTS: The infants voided an average of 1
      time per hour but with great variability. Bladder capacity increased with age
      according to the formula, 38 + 2.5 x age (months). Mean residual urine plus or
      minus standard deviation was 4.6 +/- 3.0 ml. In all infants residual volume was
      less than 5 ml. at least once during observation. CONCLUSIONS: The 4-hour voiding
      observation is an easy noninvasive method of characterizing the voiding pattern,
      focusing especially on emptying difficulties, in infants and nontoilet trained
      children.

PMID- 8863623
TI  - Analysis of shape and retractability of the prepuce in 603 Japanese boys.
AB  - PURPOSE: We evaluated preputial development in Japanese boys. MATERIALS AND
      METHODS: Preputial retractability and formation of a tight ring were evaluated in
      603 Japanese boys 0 to 15 years old. RESULTS: The incidence of a completely
      retractable prepuce gradually increased from 0% at age 6 months to 62.9% by 11 to
      15 years, while that of a tight ring decreased with age from 84.3 to 8.6%. Nine
      boys had balanoposthitis but none had a symptomatic urinary tract infection.
      CONCLUSIONS: Incomplete separation of the prepuce is common and normal in
      neonates and infants, and preputial separation progresses until adolescence.
      Awareness of these findings will eliminate unnecessary circumcision in boys.

PMID- 8863624
TI  - Role of mesenchymal-epithelial interactions in normal bladder development.
AB  - PURPOSE: To assess the role of cell-cell interactions in the development of
      bladder smooth muscle. MATERIAL AND METHODS: Bladders from 14-day rat fetuses
      (prior to smooth muscle differentiation) were isolated and digested with trypsin
      to separate the mesenchyme and epithelium. Three types of specimens were prepared
      for grafting under the renal capsule of syngeneic adult hosts: a) intact bladder
      (BL) which had been isolated from fetuses of timed pregnant rats by surgical
      methods alone; b) bladder mesenchyme (BLM) alone (urothelium removed following
      trypsinization); and c) isolated BLM recombined with bladder urothelium (BLM +
      BLE). After 2 weeks of in vivo growth the grafts were assessed by
      immunocytochemical techniques for the expression of smooth muscle cells markers
      (actin, myosin, vinculin, laminin and desmin). The same experiments were repeated
      in vitro. In the final experiment, the induction of bladder smooth muscle was
      elicited in situ across species lines. Fourteen-day rat BLM was grafted onto the
      proximal ureter of an athymic nude mouse after ipsilateral nephrectomy. RESULTS:
      Grafts of intact BL and BLM + BLE recombinants expressed smooth muscle
      differentiation. In contrast, grafts of BLM alone remained devoid of smooth
      muscle. This was also true for the in vitro studies in which, after 5 days of
      growth, BLM + BLE recombinants (n = 12) showed clear evidence of smooth muscle
      differentiation. In contrast, cultures of BLM alone (n = 12) exhibited poor
      growth without smooth muscle differentiation. In the final experiment testing the
      induction of smooth muscle across species, after 1 month in vivo growth the
      urothelium of the cut end of the ureter had invaded the grafted BLM. The BLM
      grafts (n = 3) had increased 30 times in size, and immunocytochemical staining
      showed clear expression of smooth muscle markers in the grafted BLM in proximity
      to the urothelium. CONCLUSION: We have shown that the differentiation of smooth
      muscle in the rat bladder is dependent upon an inductive interaction with the
      epithelium.

PMID- 8863625
TI  - Lipid peroxidation assessment of free radical production following release of
      obstructive uropathy.
AB  - PURPOSE: To identify if free radicals were released following relief of ureteric
      obstruction. MATERIALS AND METHODS: Free radical production was assessed by a
      high performance liquid chromatography assay of malondialdehyde (MDA) in a 24
      hour complete unilateral ureteric obstruction model in Wistar rats. RESULTS: In
      the first experiment, a rise greater than 20% above prerelease levels in renal
      venous malondialdehyde levels was observed at 8, 15, 22, and 30 minutes following
      release. At 45 and 60 minutes, levels were similar to the prerelease levels. In
      the second experiment, renal venous samples taken before release and at 10 and 20
      minutes after release in control and obstructed groups (n = 7) identified a
      significant difference (T = 10 minutes p = 0.006 and T = 20 minutes p = 0.045). A
      significant MDA rise following release occurred only in the obstructed group
      (obstruction group; MDA level T = 0 min. 1.01 mumol/l. +/- 0.13, T = 10 min. 2.12
      mumol/l. +/- 0.3 p = 0.016, T = 20 min. 2.09 mumol/l. +/- 0.28 p = 0.016. CONTROL
      GROUP: T = 0 min. 1.13 mumol/l. +/- 0.23, T = 10 min. 1.05 mumol/l. +/- 0.18 p =
      0.95, T = 20 min. 1.23 mumol/l. +/- 0.19 p = 0.67). In the third experiment, an
      attempt was made to block free radical release with allopurinol. No statistical
      difference between the control and obstructed groups with allopurinol was noted
      at 20 minutes after release. A Kruskal Wallace two-way analysis identified a
      significant difference between experiments two and three at both time periods (p
      = 0.049). CONCLUSION: This study suggests, for the first time, that free radicals
      are released after relief of ureteric obstruction and that this release is
      partially attenuated by allopurinol pretreatment.

PMID- 8863626
TI  - Evidence for aggregation in oxalate stone formation: atomic force and low voltage
      scanning electron microscopy.
AB  - PURPOSE: The aim of this investigation was to differentiate between aggregation
      and crystal growth by studying the structure of oxalate stones at high spatial
      resolution using recently developed microscopy techniques. MATERIALS AND METHODS:
      Sections from 6 complete human oxalate stones and 4 stone fragments were prepared
      by ultramicrotomy and examined by both low voltage scanning electron microscopy
      and atomic force microscopy. RESULTS: The scanning electron microscopy showed
      lamellar structures up to 10 microns. in size, consistent with previous results,
      and provided evidence that these structures were composed of smaller particles.
      The atomic force microscopy clearly showed arrays of the small particles, whose
      size varied between 500A and 2800A. CONCLUSION: Our images suggest that an
      ordered aggregation of small crystallites is responsible for oxalate stone
      formation.

PMID- 8863627
TI  - 17 beta-estradiol induced prostatitis in the rat is an autoimmune disease.
AB  - PURPOSE: Studies suggest that alteration in steroid hormone levels may be one of
      the factors causing nonbacterial prostatitis (NBP) in rats. We hypothesized that
      hormonally induced prostatitis in the rat may be an autoimmune disease. Studies
      were carried out to prove this hypothesis. MATERIALS AND METHODS: We injected 17
      beta-estradiol (E2; 250 micrograms/kg. subcutaneously) or vehicle into 1-year-old
      male rats for 30 days, and isolated and cultured the splenocytes in the presence
      of con-A (Experiment 1). Approximately 10(7) splenocytes were adoptively
      transferred into young naive syngeneic rats. To find out whether or not the
      inflammation is mediated by T-lymphocytes, a pure population of T-lymphocytes
      from E2-treated 3-month-old rats was injected into young naive syngeneic rats
      (Experiment 2). To rule out the possibility that the inflammation was due to con
      A itself, we cross-linked some T-cells with anti-CD3 antibody before adoptive
      transfer (Experiment 2). RESULTS: The recipients of splenocytes from E2-treated
      animals presented evidence of inflammation in terms of lymphocytic infiltration
      and presence of degranulated mast cells. Furthermore, we observed in these
      animals an increase in histamine-releasing peptide (HRP) levels, an indication of
      plasma extravasation. The T-cells stimulated by anti-CD3 antibody produced a
      similar degree of inflammation, thereby ruling out the possibility that the
      inflammation was due to con-A. The results also indicated that the immune
      response to antigen(s) is not dependent on the age of the animal but is dependent
      on a population of CD3+ T-cells. CONCLUSION: Our results demonstrate that
      hormonal imbalance and autoimmunity in male rats produce the symptoms of
      nonbacterial prostatitis.

PMID- 8863628
TI  - Absence of bacterial DNA in the bladder of patients with interstitial cystitis.
AB  - PURPOSE: Although bacterial infection has been long considered a possible cause
      of interstitial cystitis (IC), no definitive proof for or against this hypothesis
      has been presented so far. We have used 16S rDNA bacterial polymerase chain
      reaction to study bladder biopsies and sterile urine samples from patients
      suffering from IC. This method is sensitive and detects all known eubacteria.
      MATERIALS AND METHODS: Bladder biopsies and sterile urine samples obtained by
      transabdominal puncture were studied from 11 patients with IC. As controls we
      studied 4 patients with other urological problems leading to partly similar
      symptoms and 5 healthy individuals. RESULTS: All samples from the IC patients
      were negative. One positive sample was obtained from a woman with a history of
      urinary tract infections who suffered from nonIC ulcerative cystitis. Her sterile
      urine sample yielded Lactobacillus acidophilus. CONCLUSION: These results
      indicate that an ongoing bacterial infection is not the cause of interstitial
      cystitis.

PMID- 8863630
TI  - Contrast enhancement of PC-3 prostate cancer for magnetic resonance imaging:
      animal studies using tumor-localizing Mn-metalloporphyrin (THF-Mn-Asp).
AB  - PURPOSE: The objective of the present study was to test, in nude mouse PC-3
      tumors, the contrast enhancement of 2,4-bis(1-tetrahydro-fulfuroxyethyl)
      deuteroporphynyl(IX)-6- 7-bisaspartic acid (THF-Mn-ASP), which is a
      hematoporphyrin derivative and depresses T1 relaxation time on magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: THF-Mn-ASP or gadolinium-diethylenetriamine
      pentaacetic acid (Gd-DTPA) was intravenously administered, and MR imaging of the
      tumors transplanted into nude mice was performed on T1-weighted images. RESULTS:
      After administration of THF-Mn-Asp, the signal intensity of PC-3 tumors increased
      and the tumor/muscle intensity ratio was highest at about 1 hour. The
      tumor/muscle intensity ratio, in contrast, was highest at about 5 minutes after
      administration of Gd-DTPA. The increase in intensity ratio was 32% in THF-Mn-ASP
      and 28% in Gd-DTPA. CONCLUSION: The preliminary study suggested that THF-Mn-Asp
      has a predilection to accumulate in PC-3 tumors, and it seems to provide good
      contrast enhancement with tumor specificity for MR imaging.

PMID- 8863629
TI  - Clonal analysis of human recurrent superficial bladder cancer by
      immunohistochemistry of P53 and retinoblastoma proteins.
AB  - PURPOSE: To investigate the clonal origin of malignant cells in recurrent
      superficial bladder cancer. MATERIALS AND METHODS: We compared the protein
      expression of p53 and retinoblastoma (Rb) by immunohistochemistry using antibody
      P1801 and PMG3-245, respectively, in 13 patients at the time of primary
      superficial bladder cancer resection (6 Ta and 7 T1) and their 15 corresponding
      recurrences of disease. Mutations in p53 and Rb were inferred on the basis of
      immunoperoxidase staining. RESULTS: At the time of initial tumor resection, a p53
      mutation was observed in 5 patients (39%) and an Rb mutation was observed in 3
      (23%). The p53/Rb mutation status of recurrent bladder cancers completely matched
      their corresponding primary bladder cancer. CONCLUSIONS: The chance that
      recurrent bladder cancer originated from independent clones in this study was
      extremely small (p < 10(-6)). This result strongly supports the monoclonal origin
      of recurrent superficial bladder cancer.

PMID- 8863631
TI  - Role of spinal and peripheral alpha 2 adrenoceptors in micturition in normal
      conscious rats.
AB  - PURPOSE: To explore the potential of alpha 2-adrenoceptors in modulating
      vesicourethral function at the spinal and bladder levels. MATERIAL AND METHODS:
      Continuous cystometry was performed in normal, conscious rats, and the urodynamic
      effects of alpha 2-adrenoceptor stimulation and blockade were recorded. RESULTS:
      Given intrathecally, the selective alpha 2-adrenoceptor agonist, dexmedetomidine
      (dex) 3 nmol., decreased micturition pressure, bladder capacity, micturition
      volume and residual volume. These effects were counteracted by the selective
      alpha 2-adrenoceptor antagonist, atipamezole 30 nmol. Intrathecally dex 10 nmol.
      caused total incontinence in 9 of 9 rats. Given intra-arterially near the
      bladder, dex 6 nmol. Decreased micturition pressure, bladder capacity,
      micturition volume, residual urine and basal pressure. Atipamezole 30 nmol.
      intrathecally increased micturition pressure, bladder capacity and residual
      urine, and decreased micturition volume. Similar effects were obtained when
      atipamezole 60 nmol. was given intra-arterially. The selective alpha 2
      adrenoceptor antagonist, rauwolscine 200 nmol., had effects similar to those of
      atipamezole. CONCLUSIONS: The results show that alpha 2-adrenoceptors can
      modulate micturition in normal conscious rats both at the spinal and the
      peripheral levels.

PMID- 8863632
TI  - Urinary bladder blood flow changes during the micturition cycle in a conscious
      pig model.
AB  - PURPOSE: To develop a method using laser Doppler flowmetry in conscious pigs,
      which allows the accurate simultaneous measurement of cystometric and
      cardiovascular parameters together with changes in vesical blood flow. The animal
      model was then used to investigate the changes in blood flow in the urinary
      bladder which occur during the micturition cycle. MATERIALS AND METHODS: Seven
      large white female pigs were subjected to chronically implanted vascular access
      and urodynamic catheters as well as an intramural vesical laser Doppler probe.
      The animals underwent repeated conscious urodynamics with simultaneous
      measurement of cardiovascular, urodynamic and vesical blood flow parameters.
      RESULTS: The model shows both compliant and low-compliance behavior and allows
      greater investigation of the effects of intravesical pressure on blood flow.
      Blood flow is not altered, during compliant filling and voiding transiently
      decreases flow to 38% of resting levels, with a rapid return to normal. Low
      compliance filling results in a progressive fall in blood flow to a minimum of
      45% of normal. At all times an inverse relationship between intravesical pressure
      and blood flow is maintained. CONCLUSIONS: The pig model proved to be well suited
      to the experimental conditions and provided reproducible results. The principal
      determinant of blood flow within the wall of the bladder is the pressure within
      its lumen. During normal filling the blood supply of the bladder is able to adapt
      to the large increase in surface area which occurs, maintaining blood flow until
      the pressure increases.

PMID- 8863633
TI  - Changes in cholinergic and purinergic neurotransmission in pathologic bladder of
      chronic spinal rabbit.
AB  - PURPOSE: We evaluated the changes in cholinergic and purinergic neurotransmission
      in pathologic bladder of chronic spinal rabbits. MATERIAL AND METHODS: Detrusor
      muscle strips were obtained from normal rabbits and chronic spinal rabbits with
      detrusor hyperreflexia and detrusor sphincter dyssynergia (DSD). Muscle strips
      were mounted in an organ bath, and transmural nerve electrical field stimulation
      (EFS: supamaximal voltage, 0.5 msec. duration, 10 second trains) was performed.
      The responses to EFS and agonists were determined by recording the isometric
      tension of muscle strips. RESULTS: Both normal and pathologic detrusor strips
      contracted in a frequency dependent fashion in response to transmural electrical
      nerve stimulation. At each frequency, atropine reduced the nerve-mediated
      contraction in a dose-dependent fashion and left an atropine-resistant response
      at a concentration of 1 microM. The atropine-resistant contraction was abolished
      by desensitization of P2X-purinoceptors with repeated exposure to alpha, beta
      methylene ATP (10 microM). The atropine sensitive (cholinergic) and resistant
      (purinergic) contractions increased with an increase in frequency and reached
      maximum at 20 Hz. The relative contribution of cholinergic and purinergic
      transmission to the nerve-mediated contraction was determined at this frequency.
      In normal detrusor, the cholinergic and purinergic components were approximately
      40% and 60%. In pathologic detrusor, the cholinergic component increased to 75%
      whereas the purinergic component decreased to 25%. Exogenously administered
      acetylcholine and ATP produced dose-dependent contractions of detrusor strips.
      The concentration-response curves for each agonist did not show significant
      differences between normal and pathologic detrusor. CONCLUSION: These results
      suggest that neurotransmission is shifted to a cholinergic dominance in
      pathologic rabbit bladder affected by detrusor hyperreflexia and DSD.

PMID- 8863634
TI  - Human renal cancers resistant to IFN's antiproliferative action exhibit
      sensitivity to IFN's gene-inducing and antiviral actions.
AB  - PURPOSE: Although treatment with interferon-alpha (IFN alpha) results in tumor
      regression in a subset (< 20%) of patients with renal cell carcinoma, the
      underlying mechanisms for the resistance of renal cancer (RC) cells to IFN alpha
      is unknown. MATERIALS AND METHODS: We examined 5 RC lines resistant and 5 RC
      lines sensitive to the antiproliferative effects of IFN alpha for differences in:
      1) the number of IFN binding sites, 2) the number of signal-transducing IFNAR-1
      chains of the IFN alpha receptor, 3) IFN alpha receptor structure, 4) IFN
      stimulated gene (ISG) expression and 5) IFN alpha sensitivity in antiviral
      assays. RESULTS: No structural alterations in the IFN alpha receptor were
      detected in any RC line examined, although varying numbers of ligand binding
      sites and IFNAR-1 signal transducer chains were present. All 5 IFN-sensitive, and
      4 of 5 IFN-resistant RC lines were sensitive to the antiviral and gene-inducing
      actions of IFN alpha. CONCLUSIONS: The resistance of RC lines to IFN's
      antiproliferative action is not due to defects in ligand binding or in IFN
      receptor structure. Our results indicate that the defective antiproliferative
      response in most RC cells is not due to their failure to induce the gene-inducing
      and antiviral effects of IFN alpha.

PMID- 8863635
TI  - Inhibition of transport processes of intestinal segments following augmentation
      enterocystoplasty in rats.
AB  - PURPOSE: Sodium and chloride transport was measured by using the Ussing chamber
      voltage clamp technique to evaluate alterations occurring in ileal segments
      interposed in the urinary tract in a rat enterocystoplasty model. MATERIALS AND
      METHODS: In adult male Sprague-Dawley rats which had undergone augmentation
      ileocystoplasties 3 months earlier, intestinal segments were explanted from the
      neobladders and native ileal segments were removed separately for electrolyte
      transport and morphometric analysis. RESULTS: Basal ileal active sodium and
      chloride absorption and cyclic nucleotide-induced chloride secretion were
      attenuated in transplanted ileum in contrast to control tissue. Morphologically,
      there was villus epithelial hyperplasia, crypt hyperplasia and chronic
      inflammation in transplanted segments, but villus height:crypt length ratios were
      unchanged. CONCLUSIONS: Pathophysiologic derangements in intestinal segments
      interposed in the urinary tract include inhibition of sodium and chloride
      transport processes and mucosal hyperplasia. The use of the Ussing
      chamber/voltage clamp technique described herein offers a new approach for
      additional studies of the metabolic consequences following urinary diversion.

PMID- 8863636
TI  - An experimental study of the effect of ginkgo biloba extract on the human and
      rabbit corpus cavernosum tissue.
AB  - PURPOSE: To investigate the effect of subfractions of extract from the ginkgo on
      human and rabbit corpus cavernosal tissue and their possible use for the
      treatment of impotence. MATERIALS AND METHODS: Among the fractions of ginkgo
      biloba extract (GBE), nonginkgolide nonflavonoid fraction (NGF) has the most
      potent relaxing effect on vascular smooth muscle. We subfractionated NGF and
      speculated that some of the subfractions might have a very potent relaxing effect
      on corpus cavernosal tissue. Thereafter we have studied their effect on human and
      rabbit corpus cavernosum using organ bath and electrical field stimulation
      experiments. RESULTS: In the tissue precontracted by norepinephrine (10(-5)M.),
      corpus cavernosal tissue of human and rabbit showed relaxation in response to
      subfractions of NGF in a dose-dependent manner. 304U-1 showed the most potent
      relaxing effect (ED50 = 0.74 mg./ml. in human, ED50 = 0.66 mg./ml. in rabbit).
      304U-1 elicits pharmacological actions on corpus cavernosum smooth muscle via the
      signal transduction pathway whereby relaxation induced by 304U-1 is mediated by
      intracellular cAMP and perhaps partially by antagonizing of the adrenergic
      nervous system. A hyperpolarizing effect via potassium channel opening might also
      be related to this relaxing effect. CONCLUSION: The subfractions of NGF,
      especially 304U-1, have a relaxing effect on corpus cavernosum tissue. 304U-1,
      which showed the most potent relaxing effect, can possibly be used as a drug for
      intracavernosal injection therapy. Considering the fact that the value of ED50 is
      too high, further fractionation and in vivo study are needed before clinical use
      in an oral form.

PMID- 8863637
TI  - Protein synthesis and secretion by the rat seminiferous tubule in vivo not
      affected by experimental varicocele.
AB  - PURPOSE: Varicocele is associated with testicular dysfunction and male
      infertility. In vivo protein synthesis and secretion by the seminiferous tubules
      can be studied as an overall assessment of Sertoli cell function. The present
      experiments were undertaken to determine the effect of experimental left
      varicocele (ELV) on seminiferous tubule protein synthesis and secretion.
      MATERIALS AND METHODS: Androgen binding protein (ABP) was determined in native
      testicular interstitial fluid by radioimmunoassay. 35S-methionine was perifused
      around seminiferous tubules in vivo in testes of control rats and those with 30
      day ELV. Interstitial fluid (IF) and lumen fluid (LF) were subsequently collected
      by micropuncture, and a tubule extract (TE) was prepared. Proteins in all fluids
      were subjected to one- and two-dimensional electrophoresis and autoradiography to
      evaluate the total synthesized proteins (those in TE) as well as the secreted
      proteins (those in LF). RESULTS: Two-dimensional electrophoresis allowed
      detection of approximately 170 proteins synthesized by the seminiferous tubules
      in vivo with 60 of those being secreted into the tubule lumen within a 3-hour
      time period. Experimental left varicocele significantly reduced the concentration
      of a specific protein, ABP, in ipsilateral interstitial fluid, but more extensive
      evaluation of protein synthesis and secretion into the tubule lumen did not
      corroborate a significant change in protein synthesis and secretion by rat
      seminiferous tubules under the influence of varicocele. CONCLUSIONS: Experimental
      varicocele does not significantly alter the panel of proteins synthesized by rat
      seminiferous tubules and secreted into the lumen in vivo. At this level it does
      not appear that altered Sertoli cell function is within the primary mechanism of
      dysfunction subsequent to varicocele.

PMID- 8863638
TI  - Using drug delivery devices.

PMID- 8863639
TI  - Out on a limb.

PMID- 8863642
TI  - Choosing needlestick prevention devices.

PMID- 8863645
TI  - How to conquer the fear of codes.

PMID- 8863646
TI  - Skin care rituals that do more harm than good.

PMID- 8863647
TI  - Clinical snapshot: migraines.

PMID- 8863648
TI  - Managing postoperative pain in the elderly.

PMID- 8863650
TI  - Irradiating the thyroid. How to protect yourself and others.

PMID- 8863649
TI  - Making the transition to home care nursing.

PMID- 8863651
TI  - Emergency! Myxedema coma.

PMID- 8863652
TI  - Alternative use of PCA.

PMID- 8863653
TI  - Emerging issues in licensure and regulation.

PMID- 8863654
TI  - Adding an 'at home' path to your discharge plan.

PMID- 8863655
TI  - Patients' privacy on the line.

PMID- 8863656
TI  - Rous-Whipple Award Lecture. Role of complement in lung inflammatory injury.

PMID- 8863657
TI  - Expression and distribution of amyloid precursor protein-like protein-2 in
      Alzheimer's disease and in normal brain.
AB  - Amyloid precursor-like protein-2 (APLP-2) belongs to a family of homologous
      amyloid precursor-like proteins. In the present study we report on the expression
      and distribution of APLP-2 in fetal and adult human brain and in brains of
      patients with Alzheimer's disease. We demonstrate that APLP-2 mRNAs encoding
      isoforms predicted to undergo post-translational modification by chondroitin
      sulfate glycosaminoglycans are elevated in fetal and aging brains relative to the
      brains of young adults. Immunocytochemical labeling with APLP-2-specific
      antibodies demonstrates APLP-2 immunoreactivity in cytoplasmic compartments in
      neurons and astrocytes, in large part overlapping the distribution of the amyloid
      precursor protein. In Alzheimer's disease brain, APLP-2 antibodies also label a
      subset of neuritic plaques. APLP-2 immunoreactivity is particularly conspicuous
      in large dystrophic neurites that also label with antibodies specific for APP and
      chromogranin A. In view of the age-dependent increase in levels of chondroitin
      sulfate glycosaminoglycan-modified forms of APLP-2 in aging brain and the
      accumulation of APLP-2 in dystrophic presynaptic elements, we suggest that APLP-2
      may play roles in neuronal sprouting or in the aggregation, deposition, and/or
      persistence of beta-amyloid deposits.

PMID- 8863659
TI  - CD79 alpha expression in acute myeloid leukemia. High frequency of expression in
      acute promyelocytic leukemia.
AB  - CD79 alpha is a subunit of an intracytoplasmic protein reported to be specific
      for B lymphocytes, including immature B lineage cells. To evaluate expression of
      the CD79 alpha antigen in acute myeloid leukemia (AML), we studied forty-eight
      cases of AML by paraffin section immunohistochemistry. The cases included four
      MO, nine M1, nine M2, ten M3, ten M4, and six M5 AMLs using criteria of the
      French-American-British cooperative group. Eleven cases demonstrated cytoplasmic
      staining for the CD79 alpha antigen, including one M1, nine M3, and one M5 AML.
      These CD79 alpha-positive cases represented 5% of all non-promyelocytic AMLs and
      90% of all acute promyelocytic leukemias studied. All acute promyelocytic
      leukemias had the characteristic t(15;17)(q24;q21), including two cases of the
      microgranular variant (M3v). No other B-lineage-associated antigens were found in
      the CD79 alpha-positive cases, with the exception of a subpopulation of CD19
      positive leukemic cells in one patient. The two non-promyelocytic leukemias that
      expressed CD79 alpha had no evidence of t(15;17) and did not express any
      additional B-lineage-associated antigens that might suggest a mixed lineage
      proliferation. This study demonstrates that CD79 alpha expression in acute
      leukemia is not restricted to B-lineage acute lymphoblastic leukemias and that
      CD79 alpha expression is frequently associated with t(15;17) acute myeloid
      leukemia.

PMID- 8863658
TI  - Localization of simian immunodeficiency virus nucleic acid and antigen in brains
      of fetal macaques inoculated in utero.
AB  - Neurological dysfunction has been shown to be associated with human
      immunodeficiency virus (HIV) infection. The incidence of these abnormalities is
      greater in HIV-infected children when compared with adults, and the patterns of
      neurological disease are also known to differ from those observed in the adult
      population. The reasons for these differences are unclear but are most likely
      related to the immaturity of the host's immune and central nervous systems at the
      time of infection. This is thought to be particularly true for infants infected
      with HIV prenatally. To examine these questions, the brains of fetal rhesus
      macaques that were infected with SIVmac251 at various time points in utero were
      examined. Direct fetal inoculations were performed on gestational day (GD) 65 (n
      = 8; early second trimester), GD 110 (n = 4; early third trimester) and GD 130 (n
      = 2; mid third trimester), with harvest of fetal tissues on GD 80, 100, 130, or
      145. Eleven sham controls were included with harvest at correlative time points.
      Specimens were examined by routine histology, immunohistochemistry, and in situ
      hybridization to localize viral antigens and SIV nucleic acid. Histologically,
      scattered glial nodules, spongiosis, and mineralization were found in the basal
      ganglia and deep white matter in 4 of the 14 fetuses (3 inoculated on GD 65 and
      one on GD 110). These fetuses and those without histological lesions had viral
      nucleic acid and SIV antigen in the stroma of the choroid plexus, meninges, and
      external granular layer of the cerebellum and in columns of cells in the cortical
      plate. In contrast to juvenile and adult macaques, very few SIV-positive
      perivascular mononuclear cells were present. These findings suggest that SIV has
      a different distribution in the brain of fetal macaques after direct infection
      when compared with adult or juvenile animals. Furthermore, the results of these
      studies suggest that differences in neurological disease between pediatric and
      adult patients with acquired immune deficiency syndrome are most likely related
      to the time of infection.

PMID- 8863660
TI  - Detection of Epstein-Barr virus-infected mucosal lymphocytes in nasal polyps.
AB  - Primary nasal lymphomas of T or NK cell origin are known to be associated with
      Epstein-Barr virus (EBV). However, it is not known whether EBV is normally
      present in nasal mucosa as distinct to nasopharyngeal tissue. This study
      investigates the prevalence of EBV infection in 13 cases of nasal polyps. EBV DNA
      was detected in 2 of 13 (15%) by Southern blot hybridization and in 9 of 13 (69%)
      by polymerase chain reaction. In situ hybridization for EBV-encoded small nuclear
      RNAs (EBER) was positive in 11 of 13 (85%) cases; the virus was present in
      stromal lymphocytes only and not in the epithelial cells. Immunohistochemistry
      for EBV proteins in 7 cases revealed EBV nuclear antigen (EBNA)-2, latent
      membrane protein (LMP)-1, and ZEBRA (the switch protein encoded by gene BZLF1)
      expression in rare isolated stromal lymphocytes in 3 cases. Double immunostaining
      in 1 case showed that the LMP-1+ cells were B or T cells. Immunohistochemistry
      for EBV lytic proteins showed very rare viral capsid antigen (VCA)+ and membrane
      antigen (MA)+ cells in 1 case and very rare diffuse early antigen (EA-D)+ and
      VCA+ cells in 1 other case. The expression of ZEBRA, EA-D, VCA, and MA suggested
      a disruption of latency in very rare stromal lymphocytes leading to a productive
      cycle. Although the incidence of EBV positivity in nasal polyps in our population
      is high (85%), very low numbers of EBV+ cells are found in each case.
      Nevertheless, they indicate that nasal mucosa could be one of the sites of EBV
      persistence through a low level of infection of the resident lymphocytes and
      thereby provide a possible setting for the emergence of virally associated tumors
      in this site.

PMID- 8863661
TI  - De Novo renal expression of macrophage migration inhibitory factor during the
      development of rat crescentic glomerulonephritis.
AB  - Macrophage migration inhibitory factor (MIF), a key mediator of the delayed-type
      hypersensitivity response, was originally thought to be produced by activated T
      cells. However, recent studies have found that MIF is produced in many cell types
      including monocytes/macrophages and anterior pituitary cells. The current study
      has examined MIF expression in normal and diseased kidney using in situ
      hybridization, immunohistochemistry, and Northern blotting. MIF mRNA and protein
      are constitutively expressed in normal kidney, being largely restricted to
      tubular epithelial cells and some glomerular visceral and parietal epithelial
      cells. During the development of rat anti-glomerular basement membrane
      glomerulonephritis, a model of macrophage-mediated renal injury, there was marked
      de novo expression of MIF by intrinsic kidney cells including endothelium and
      glomerular and tubular epithelial cells. Up-regulation of MIF expression
      correlated with macrophage accumulation within the glomerulus (P < 0.001) and
      tubulointerstitium (P < 0.001). Of significance, the accumulation of macrophages
      was exclusively localized to areas of strong MIF expression, contributing to
      focal glomerular and tubulointerstitial lesion formation. In addition, up
      regulation of MIF expression by parietal epithelial cells was associated with
      macrophage accumulation within Bowman's space and crescent formation. Combined in
      situ hybridization and immunostaining also demonstrated MIF expression by
      macrophages, T cells, and fibroblast-like cells within renal lesions. In
      conclusion, these data provide the first demonstration that renal epithelial
      cells are a major source of MIF in both normal and diseased kidney. Furthermore,
      the up-regulation of MIF expression may play an important role in macrophage
      accumulation and progressive renal injury in rat crescentic glomerulonephritis.

PMID- 8863663
TI  - Differentiation-associated overexpression of the cyclin-dependent kinase
      inhibitor p21waf-1 in human cutaneous squamous cell carcinoma.
AB  - p21waf-1 negatively regulates the cell cycle by inhibiting the activity of cyclin
      dependent kinases. As p21waf-1 is a probable tumor suppressor, we sought to
      determine whether this cyclin-dependent kinase inhibitor is abnormally regulated
      in human cutaneous squamous cell carcinoma (SCC). An immunohistochemical
      technique was employed to assay p21waf-1 protein in SCCs chosen from sun-exposed
      and anogenital sites. We observed that p21waf-1 was greatly overexpressed in SCC
      versus adjacent benign epithelium. Furthermore, expression of p21waf-1 was
      consistently elevated in the superficial, differentiated cells versus basal
      keratinocytes. p21waf-1 expression correlated with the proliferative state of the
      cancers as measured by MIB-1 immunostaining. In vitro, keratinocytes grown in
      supplemented media upregulated p21waf-1 during differentiation, supporting our in
      vivo observations. We conclude that p21waf-1 overexpression is associated with
      differentiation in proliferating SCC but is not sufficient to suppress cancer
      development.

PMID- 8863665
TI  - Regulation of carcinoembryonic antigen expression in human colon carcinoma cells
      by the organ microenvironment.
AB  - The expression of carcinoembryonic antigen (CEA) is thought to be involved in
      homotypic adhesion and has been associated with the progression of human colon
      carcinomas (HCC) to the metastatic state. Three cell lines established from
      surgical specimens of Dukes' stage D (KM20) or Dukes' stage B (KM12C, KM12SM)
      with high and low preoperative CEA serum levels, respectively, were studied
      subsequent to growth in culture, in the subcutis (ectopic) or cecal wall
      (orthotopic) of nude mice. In all cell lines, CEA expression was higher in cecal
      tumors than in subcutaneous lesions. The degree of differentiation and CEA
      expression by HCC growing in the cecal wall of nude mice correlated with the
      pathological diagnosis and preoperative CEA level of the original patients. To
      better understand the regulation of CEA expression, the HCC cells were grown in
      culture as sparse and confluent monolayers or as multicell spheroids. The CEA
      expression level increased in all three cell lines growing as confluent
      monolayers and was highest in multicell spheroids. Treatment of sparse monolayer
      cultures of KM12SM cells with mitomycin-C inhibited cell division and was
      associated with higher production of CEA protein. Moreover, conditioned media
      from confluent monolayer cultures or from spheroids up-regulated CEA production
      in sparse monolayer cells. These data show that CEA expression in HCC cells may
      be regulated by cell density and by factors from the organ environment.

PMID- 8863664
TI  - Relationship between CD44 expression and cell proliferation in epithelium and
      stroma of colorectal neoplasms.
AB  - The cell surface glycoprotein CD44 is expressed primarily in the region of cell
      replication in the lower crypt epithelium of colorectal mucosa, and its
      expression is markedly increased in colorectal neoplasms, suggesting that
      expression is linked to proliferation. The association between CD44 expression
      and replication in individual cells was therefore analyzed by double-label
      immunohistochemistry for CD44 and the cell-cycle-dependent protein proliferating
      cell nuclear antigen (PCNA). Enhanced expression of CD44 in colorectal neoplasms
      occurred not only in epithelial cells but also in stromal cells, including
      lymphocytes and macrophages. On a topographical basis, the cellular localization
      of CD44 and PCNA were commonly different. Quantitatively, in all cell types
      studied (epithelial cells and stroma of colorectal mucosa, adenomas, and
      carcinomas) PCNA was present most frequently in cells lacking CD44. Statistical
      analysis by logistic regression models indicated that cells negative for CD44 had
      a higher probability of being positive for PCNA than did cells positive for CD44
      (P < 0.001). These data suggest that the enhanced level of CD44 in colorectal
      neoplasms is asynchronous with cell replication and reflects mechanisms that act
      on nonproliferative stromal lymphocytes and other mononuclear cells as well as
      the epithelial cells.

PMID- 8863662
TI  - Exon-specific DNA hypomethylation of the p53 gene of rat colon induced by
      dimethylhydrazine. Modulation by dietary folate.
AB  - Folate deficiency enhances colorectal carcinogenesis in dimethylhydrazine-treated
      rats. Folate is an important mediator of DNA methylation, an epigenetic
      modification of DNA that is known to be dysregulated in the early stages of
      colorectal cancer. This study investigated the effect of dimethylhydrazine on DNA
      methylation of the colonic p53 gene and the modulation of this effect by dietary
      folate. Sprague-Dawley rats were fed diets containing 0, 2, 8, or 40 mg of
      folate/kg of diet. Five weeks after diet initiation, dimethylhydrazine was
      injected weekly for fifteen weeks. Folate-depleted and folate-replete control
      animals did not receive dimethylhydrazine and were fed the 0- and 8-mg folate
      diets, respectively. The extent of p53 methylation was determined by a
      quantitative HpaII-polymerase chain reaction. In exons 6 and 7, significant p53
      hypomethylation was observed in all dimethylhydrazine-treated rats relative to
      controls (P < 0.01), independent of dietary folate. In exon 8, significant p53
      hypomethylation was observed only in the dimethylhydrazine-treated folate
      depleted rats compared with controls (P = 0.038) and was effectively overcome by
      increasing levels of dietary folate (P = 0.008). In this model, dimethylhydrazine
      induces exon-specific p53 hypomethylation. In some exons, this occurs independent
      of dietary folate, and in others, increasing levels of dietary folate effectively
      override the induction of hypomethylation in a dose-responsive manner. This may
      be a mechanism by which increasing levels of dietary folate inhibit colorectal
      carcinogenesis.

PMID- 8863666
TI  - Classification of hepatocellular carcinoma according to hepatocellular and
      biliary differentiation markers. Clinical and biological implications.
AB  - Hepatocellular carcinoma (HCC) is a heterogeneous disease. HCC derived from
      different stages of cellular differentiation may have different clinical and
      pathobiological behavior. To test the hypothesis that HCC can be classified into
      two types based on its phenotypic markers (hepatocellular and biliary
      differentiation), liver tissues from 290 Chinese patients with HCC were studied.
      Expression of hepatocytic differentiation marker (HEP-PAR-reactive antigen),
      biliary differentiation markers (AE1-AE3, cytokeratin-19), proliferation markers
      (Ki-67, proliferating cell nuclear antigen), alpha-fetoprotein, p53, and
      transforming growth factor-alpha in the tumor tissue were assessed by
      immunohistochemistry. Hepatocytic differentiation marker was detected in 99.7%
      and biliary differentiation markers were detected in 29.3% of these tumors.
      Clinically, no patient with HCC with biliary markers survived for more than 27
      weeks compared with a 22.6% survival rate in patients with HCC negative for
      biliary markers. HCCs positive for the biliary differentiation markers showed
      features of more aggressive disease in terms of poorer cellular differentiation
      (P < 0.001) and high-level expression of proliferation markers (Ki-67, P < 0.001;
      proliferating cell nuclear antigen, P = 0.0114) compared with HCCs without
      biliary markers. HCCs with biliary markers also had a higher level of expression
      of alpha-fetoprotein (P < 0.001) and p53 (P = 0.0077). Classification of HCCs
      based on its phenotypic (differentiation) markers has both clinical and
      pathobiological implications.

PMID- 8863668
TI  - Comparison of fluorescence in situ hybridization analysis of isolated nuclei and
      routine histological sections from paraffin-embedded prostatic adenocarcinoma
      specimens.
AB  - Fluorescence in situ hybridization (FISH) is a powerful tool for quantitative
      analysis of chromosomes and genes and can be applied in a variety of specimens,
      including cell cultures, isolated nuclei from fresh and fixed tissues, and
      histological tissue sections. However, the results of FISH analysis of isolated
      nuclei in prostate cancer have not been previously compared with those from
      histological sections from the paraffin-embedded tissue blocks. To compare these
      methods, we studied isolated nuclei derived from 50-microns sections and adjacent
      5-microns tissue sections from 10 cases of benign nodular hyperplasia of the
      prostate and 16 cases of prostatic carcinoma. FISH analysis employed centromere
      specific probes for chromosomes 7, 8, 11, and 12. In benign tissue, the
      percentage of nuclei with three or more signals for chromosomes 7, 8, 11, and 12
      was less than 3% for both isolated nuclei and tissue sections. However, the
      percentage of nuclei with no and one signals was less than 8% for isolated nuclei
      and more than 24% for tissue sections. In prostatic carcinoma, numeric
      chromosomal anomalies were found in 75% of cases by both FISH methods. However,
      isolated nuclei had more chromosomal tetrasomy than tissue sections (mean, 9.2 to
      11.0% versus 5.1 to 5.6%, respectively). Conversely, intratumor heterogeneity of
      chromosomal anomalies was identified in 5 cases by FISH analysis of tissue
      sections but not in isolated nuclei. Cancer ploidy analysis by FISH correlated
      well with ploidy analysis by flow cytometry, although FISH was more sensitive for
      aneuploidy. We conclude that FISH analysis of isolated nuclei and histological
      tissue sections from paraffin blocks are reliable methods for detection of
      chromosomal anomalies in archival tissue of prostate cancer, although each method
      has advantages and disadvantages.

PMID- 8863667
TI  - Neoplastic transformation of prostatic and urogenital epithelium by the polyoma
      virus middle T gene.
AB  - Male transgenic mice expressing the polyomavirus middle T (PyV-MT) gene exhibited
      growth and developmental abnormalities in prostatic and other urogenital
      epithelium. Expression of PyV-MT was directed to these tissues by a novel,
      androgen-inducible expression vector based on the rat C3(1) gene. Epithelial
      growth disturbances (hyperplasia, dysplasia, and invasive carcinoma) were
      observed in the ventral and dorsal prostate, coagulating gland, epididymis, and
      vas deferens. The abnormalities were characterized by histological
      disorganization, nuclear pleomorphism, increased mitoses, and abnormal DNA
      content. Transgene transcription was detected in affected tissues, indicating
      that the C3(1)-based vector targeted androgen-sensitive urogenital tissues,
      especially the prostate. These results demonstrated that expression of a gene,
      the protein of which is known to interact with cellular proteins involved in
      signal transduction, dramatically disrupted urogenital growth and development.

PMID- 8863669
TI  - Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and
      genetic features.
AB  - The tuberous sclerosis complex (TSC) is a multisystem autosomal dominant disorder
      characterized by seizures, mental retardation, and hamartomas. Patients with TSC
      have been reported to develop renal cell carcinomas (RCC) with increased
      frequency, an observation that is supported by the Eker rat model. To address the
      role of the tuberous sclerosis tumor suppressor genes in the pathogenesis of RCC,
      we studied six TSC-associated RCCs. Our findings suggest that some TSC-associated
      RCCs have clinical, pathological, or genetic features distinguishing them from
      sporadic RCC. Clinically, the TSC-associated tumors occurred at a younger age
      (mean, 36 years) than sporadic tumors and occurred primarily in women. Four of
      the six patients died of metastatic disease. Pathologically, five tumors
      displayed clear cell morphology. Of those five, two had high-grade spindle cell
      areas and one had granular cell histology in addition to the clear cell areas. A
      sixth tumor was anaplastic throughout. Four of the six tumors immunostained
      positively for a melanocyte-associated marker, HMB-45. HMB-45 positivity has been
      seen in two other TSC lesions: renal angiomyolipomas and pulmonary
      lymphangiomyomatosis. Five tumors were analyzed for loss of heterozygosity. Two
      had loss of heterozygosity on chromosome 9q34 and one had loss of heterozygosity
      on chromosome 16p13. We conclude that TSC-associated RCCs occur at an earlier age
      than sporadic RCCs, that some TSC-associated renal carcinomas have a different
      immunophenotype than sporadic RCCs, and that the TSC tumor suppressor genes may
      play a specific pathogenic role in these tumors.

PMID- 8863670
TI  - Expression of Met/hepatocyte growth factor receptor gene and malignant behavior
      of musculoskeletal tumors.
AB  - Overexpression of the hepatocyte growth factor receptor (Met/HGF receptor), a
      transmembrane tyrosine kinase encoded by the met proto-oncogene, has been
      associated with tumor progression in different human carcinomas. More recently,
      the Met/HGF receptor has also been described in tumor cell lines of mesenchymal
      origin, suggesting the existence of an autocrine loop that may contribute to the
      pathogenesis of sarcomas. In this study, we analyzed the expression of Met/HGF
      receptor by Western blotting and immunohistochemistry in frozen samples of 87
      primary tumors of bone and soft tissues. Among benign tumors, overexpression was
      consistently found only in giant-cell tumor, a locally aggressive lesion that may
      also, although rarely, spread to the lung. Among malignant lesions, the presence
      of the Met/HGF receptor was detected in a relevant percentage of primaries and in
      almost all of the recurrences. The highest levels of Met/HGF receptor were found
      in osteosarcoma, a highly aggressive tumor that typically permeates the host bone
      and rapidly expands to the soft tissues. On the contrary, only low levels of
      Met/HGF receptor were found in chondrosarcoma, a slowly growing tumor that
      usually expands without massive destruction of the surrounding structures. These
      data indicate an association of Met/HGF expression with local aggressiveness in
      human mesenchymal tumors. The finding of Met/HGF receptor overexpression in all
      of the osteosarcomas suggests a role for the met proto-oncogene in the
      pathogenesis of this tumor.

PMID- 8863672
TI  - Abnormal expression of plasminogen activator inhibitors in patients with
      gestational trophoblastic disease.
AB  - We previously reported significantly elevated levels of plasminogen activator
      inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe
      pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As
      increases in PAI-1 may contribute to the placental alterations that occur in pre
      eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and
      several other components of the fibrinolytic system in patients with
      trophoblastic disease. Significant increases in plasma PAI-1 and decreases in
      plasma PAI-2 levels were observed in molar pregnancies when compared with the
      levels in normal pregnant women of similar gestational age. PAI-1 antigen levels
      also were increased, and PAI-2 levels were decreased in placenta from women with
      molar pregnancies compared with placenta obtained by spontaneous abortion.
      Immunohistochemical analysis revealed strong positive and specific staining of
      PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak
      staining of PAI-2. No association between the distribution of PAI-1 and
      vitronectin was found, and no specific signal for tissue type PA, urokinase type
      PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ
      hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from
      molar pregnancies in comparison with placenta from abortions. These results
      demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest
      that localized elevated levels of PAI-1 may contribute to the hemostatic problems
      associated with this disorder.

PMID- 8863671
TI  - Germ cell tumors of the testis overexpress wild-type p53.
AB  - Several recent studies have suggested that testicular germ cell tumors express
      high levels of wild-type p53 protein. To clarify and confirm this unexpected
      result, we have investigated seminomatous and nonseminomatous germ cell tumors at
      the genomic, mRNA, and protein levels. Thirty-five tumors were examined for p53
      overexpression using antibodies directed against the p53 (PAb1801, PAb240, and
      CM1), mdm2 (IF2), and p21Waf1/Clp1 (EA10) proteins. Thirty-two tumors were
      screened for p53 mutations by single-strand conformation polymorphism analysis.
      Eighteen tumors were screened with a functional assay that tests the
      transcriptional competence of human p53 protein expressed in yeast. On frozen
      sections, 100, 65, 35, 73, and 0% of tumors reacted with the CM1, PAb240,
      PAb1801, IF2, and EA10 antibodies, respectively. No p53 mutations were detected
      by single-strand conformation polymorphism or by functional assay. The fact that
      many tumors overexpress wild-type p53 but not mdm2 rules out mdm2 overexpression
      as a general explanation for the presence of wild-type p53 in these tumors. The
      absence of p21 overexpression suggests that p53 may be unable to activate
      transcription of critical target genes, which may explain why the presence of
      wild-type p53 is tolerated in this tumor type, although the mechanism for this
      transcriptional inactivity remains to be established.

PMID- 8863673
TI  - Immunohistochemical study of metalloproteinases and their tissue inhibitors in
      the lungs of patients with diffuse alveolar damage and idiopathic pulmonary
      fibrosis.
AB  - Immunohistochemical and confocal microscopic studies of the localization of
      matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV
      collagen were made in lung tissues from patients with normal pulmonary histology
      (n = 3), diffuse alveolar damage (n = 14), and idiopathic pulmonary fibrosis (n =
      12). Pretreatment with pepsin revealed otherwise undetectable MMP- and TIMP
      immunoreactive sites. In normal lung, MMP-2, MMP-9, TIMP-1, and TIMP-2 were
      localized in ciliated cells, endothelial cells, pneumocytes, macrophages, and
      smooth muscle cells; fibroblasts showed a strong reaction only for MMP-2. Only
      TIMP-2 showed co-localization with type IV collagen. Myofibroblasts and
      epithelial cells expressed increased reactivity for MMPs and TIMPs in both
      disorders. The reactivities for MMPs and TIMPs were stronger in diffuse alveolar
      damage. MMP-2 showed focal co-localization in capillary endothelial and disrupted
      epithelial basement membranes, suggesting activation of collagenolysis. A
      protective effect against this lysis was suggested by the extensive co
      localization of TIMP-2 with type IV collagen and fibrillar collagens. Alveolar
      buds showed increased reactivity for MMPs and TIMPs in their lining epithelial
      cells, myofibroblasts, and their basement membranes; however, their matrices were
      mostly unreactive. These findings emphasize the complexity of the roles of MMPs
      and TIMPs in collagen turnover in diffuse alvcolar damage and idiopathic
      pulmonary fibrosis.

PMID- 8863674
TI  - Mesenchymal cell activation is the rate-limiting step of granulation tissue
      induction.
AB  - During wound repair a 3-day lag occurs between injury and granulation tissue
      development. When full-thickness, 8-mm-round, excisional wounds were made in the
      paravertebral skin of outbred Yorkshire pigs and harvested at various times, no
      granulation tissue was observed before day 4. Day 4 wounds were 3% filled with
      granulation tissue, day 5 wounds 48% filled, and day 7 wounds 88% filled. The
      prerequisites for granulation tissue induction are not known but hypothetically
      include fibrin matrix maturation or cell activation. To examine whether matrix
      maturation was necessary, wounds were allowed to heal for 5 or 7 days and then
      aggressively curetted, resulting in the formation of fresh fibrin clots in the
      newly formed wound spaces. In contrast to original wounds, no lag phase was
      observed; wounds curetted on day 5 were 23% filled with granulation tissue 1 day
      later and 99% filled 3 days later, whereas wounds curetted on day 7 were 47%
      filled 1 day later and completely filled within 2 days. Thus, granulation tissue
      formation resumed promptly and independently of fibrin clot matrix maturation.
      This observation suggested that mesenchymal cell activation might be the rate
      limiting step in granulation tissue formation. To address this hypothesis more
      directly, cultured porcine or human fibroblasts, grown to 80% confluence in
      Dulbecco's minimal essential medium plus 10% fetal calf serum, were added to new
      wounds. These wounds were sealed with a freshly made exogenous fibrin clot. In
      some wounds, platelet releasate was added to the fibrin clot. Granulation tissue
      did not form in day 3 wounds, which had received either fibrin alone, fibrin and
      platelet releasate, or fibrin and fibroblasts. In contrast, granulation tissue
      was observed in wounds receiving fibrin, human fibroblasts, and platelet
      releasate. By day 4, wounds receiving cultured human fibroblasts, fibrin, and
      platelet releasate were 14% filled with granulation tissue compared with less
      than 4% granulation tissue in control wounds. Thus, fibroblast activation is a
      limiting step of granulation tissue formation, and continued cell stimulation is
      required for accelerated development.

PMID- 8863675
TI  - Repopulation of murine Kupffer cells after intravenous administration of liposome
      encapsulated dichloromethylene diphosphonate.
AB  - Kupffer cells were selectively eliminated in mice by the intravenous
      administration of liposome-entrapped dichloromethylene diphosphonate. At 5 days,
      small peroxidase-negative and acid-phosphatase-weakly-positive macrophages
      appeared, increased in number, and differentiated into peroxidase- and acid
      phosphatase-positive Kupffer cells. Repopulating small macrophages actively
      proliferated, and the number of Kupffer cells returned to the normal level by day
      14. The numbers of macrophage precursors in the liver as detected by the
      monoclonal antibodies ER-MP20 and ER-MP58 increased after liposome-entrapped
      dichloromethylene diphosphonate injection. ER-MP58-positive cells proliferated
      and differentiated into ER-MP20-positive cells and eventually into BM8-positive
      Kupffer cells in the liver. Bone-marrow-derived ER-MP58-positive cells were also
      detectable in the liver and differentiated into ER-MP20-positive cells, but they
      did not become BM8-positive macrophages. Macrophage colony-stimulating factor
      mRNA expression was enhanced in the liver 1 day after injection. The
      administration of macrophage colony-stimulating factor did not shorten the period
      of Kupffer cell depletion but increased the number and the proliferative capacity
      of repopulating Kupffer cells. These findings implied that repopulating Kupffer
      cells are derived from a macrophage precursor pool in the liver rather than from
      bone-marrow-derived monocytes. Local production of macrophage colony-stimulating
      factor in the liver plays a crucial role in the differentiation, maturation, and
      proliferation of Kupffer cells.

PMID- 8863676
TI  - Role of matrix metalloproteinases in failure to re-epithelialize after corneal
      injury.
AB  - Delayed re-epithelialization of the cornea after injury usually precedes stromal
      ulceration. Previous findings using a rat thermal injury model suggested that re
      epithelialization is impeded by products of resident corneal cells, which destroy
      adhesive structures at the basement membrane zone. In this study, we provide
      additional evidence for this concept. Failure to re-epithelialize was found to
      correlate with an increase in the amounts of gelatinolytic matrix
      metalloproteinases present in the rat cornea. One of these gelatinases,
      gelatinase B, is synthesized by the resident corneal cells, and inhibitions of
      its synthesis correlated with inhibition of basement membrane dissolution. The
      matrix metalloproteinases collagenase and stromelysin are also synthesized by
      resident corneal cells in thermally injured corneas of rabbits, but the timing of
      bulk enzyme synthesis correlated more closely with deposition of repair tissue in
      the stroma than with failure to re-epithelialize. Nevertheless, in human corneas
      with repair defects, gelatinase B and collagenase are synthesized by cells in the
      basal layer of the epithelium directly adjacent to the basement membrane,
      suggesting that both could participate in dissolution of this structure.
      Importantly, treatment of thermally injured corneas with a synthetic inhibitor of
      matrix metalloproteinases significantly improved basement membrane integrity.
      These data support the concept that over-expression of matrix metalloproteinases
      by resident corneal cells impedes re-epithelialization after some types of
      corneal injury.

PMID- 8863678
TI  - Lipoproteins accumulate in immune deposits and are modified by lipid peroxidation
      in passive Heymann nephritis.
AB  - Proteinuria in passive Heymann nephritis is primarily caused by reactive oxygen
      species that are produced by glomerular cells. Reactive oxygen species apparently
      exert their damaging effects on the glomerular filter by lipid peroxidation and
      subsequent adduct formation on matrix proteins of glomerular basement membranes.
      This raised the question as to the source of polyunsaturated fatty acids required
      as substrates for lipid peroxidation. Here we have localized by
      immunocytochemistry rat apolipoprotein E and apolipoprotein B within
      subepithelial immune deposits. Moreover, apolipoprotein B extracted from isolated
      glomeruli of proteinuric passive Heymann nephritis rats shows degradation and
      lipid peroxidation adduct formation, similar to apoproteins of oxidized
      lipoproteins in atherosclerotic lesions. These data provide evidence that
      lipoproteins accumulate within immune deposits and suggest that their lipids
      generate lipid-peroxidation-derived reactive compounds.

PMID- 8863677
TI  - Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by
      intratracheal or intravenous challenge with Corynebacterium parvum in sensitized
      rats.
AB  - Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous
      diseases of the lung for which clinical presentation and anatomic site of
      granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled
      antigens, whereas the nature and source of the inciting antigen in sarcoidosis is
      unknown. To test the hypothesis that the route via which antigen is introduced to
      the lung contributes to the clinicopathological presentation of pulmonary
      granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium
      parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C.
      parvum. The granulomatous inflammation elicited by i.t. challenge predominantly
      involved alveolar spaces and histologically simulated extrinsic allergic
      alveolitis. In contrast, the inflammation induced by i.v. challenge was
      characterized by granulomatous angiitis and interstitial inflammation simulating
      sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar
      fluid, which reflect inflammation in the intra-alveolar compartment, were much
      more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor,
      interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and
      protein expression occurred in each model. In conclusion, i.t. or i.v. challenge
      with C. parvum in sensitized rats caused pulmonary granulomatous inflammation
      that was histologically similar to human extrinsic allergic alveolitis and
      sarcoidosis, respectively. Although the soluble and cellular mediators of
      granulomatous inflammation were qualitatively similar in both disease models, the
      differing anatomic source of the same antigenic challenge was responsible for
      differing clinicopathological presentations.

PMID- 8863679
TI  - Connexin expression and intercellular communication in two- and three-dimensional
      in vitro cultures of human bladder carcinoma.
AB  - The identification of gap-junctional proteins (connexins) and the preparation of
      related antibodies provides new tools to study patterns of intercellular
      communication in tumors. Focusing on the biology of human bladder carcinoma, we
      compared the expression of gap-junctional proteins (connexins Cx26, Cx32, and
      Cx43) with a dye-coupling assay for gap-junctional intercellular communication in
      three cell lines with different urothelial differentiation. The cell lines HCV
      29, RT4, and J82 were initially grown as monolayers of different ages. Connexin
      expression was found mostly positive over the time of culture and found
      constantly negative only in J82 cells for Cx26 and HCV-29 cells for Cx32. In HCV
      29 cells, Cx26 increased in positivity over the time of culture. Western blotting
      with the antibodies confirmed the findings. Comparisons of dye transfer using
      Lucifer Yellow showed an increase of coupling in the normal urothelial cell line
      HCV-29 in contrast to a decrease of coupling in the tumor cell lines. Data were
      extended by multicellular spheroid (MCS) co-cultures with the stromal fibroblast
      line N1. In three-dimensional cultures as MCSs, Cx26 was increased in proximity
      of RT4 tumor cells to fibroblasts, and positivity was maintained in J82 cells. E
      cadherin expression in cell lines showed no change in dependence of growth state.
      The data suggest that Cx26 plays a role in negative growth control or
      differentiation of urothelial cells. Preliminary comparative data on normal and
      neoplastic urothelium show all three connexins in normal urothelium, in contrast
      to varying amounts of Cx43 and low amounts of Cx32 in tumors and evident loss of
      Cx26 in low-grade tumors. Discrepancies between monolayer and MCS cultures are
      most likely due to higher differentiation in MCSs, and the continuation of
      systematic work with heterologous MCSs is indicated for more information on the
      role of gap-junctional proteins in human tumors.

PMID- 8863680
TI  - K-ras and p53 mutations in hamster pancreatic ductal adenocarcinomas and cell
      lines.
AB  - K-ras and p53 gene alterations are frequently found in human pancreatic
      carcinomas and cell lines. The aim of this study was to analyze for the presence
      of K-ras and p53 gene mutations in hamster pancreatic tumors and cell lines.
      Mutations at the first coding exon of the K-ras gene and in exons V to VIII of
      the hamster p53 gene were analyzed in six cell lines (H2T, PC1, PC1.2, PC1.0, WD,
      and PD) and in N-nitroso-bis(2-oxopropyl)amine-induced pancreatic (n = 9) and
      extra-pancreatic (n = 4) tumors. K-ras mutations were present in seven of the
      nine pancreatic tumors and in all extra-pancreatic tumors. No p53 mutations were
      detected in the tumors. All cell lines analyzed contained K-ras mutations.
      Moreover, four of the six cell lines contained single amino acid substitutions in
      the p53 gene. Cell lines derived from nitrosamine-induced pancreatic tumors in
      the hamster contained K-ras and p53 alterations similar to those found in cell
      lines derived from human pancreatic carcinomas.

PMID- 8863681
TI  - Differential expression of laminin 5 (alpha 3 beta 3 gamma 2) by human malignant
      and normal prostate.
AB  - Laminin 5 is an extracellular matrix protein integral to the formation of the
      hemidesmosomes that attach normal basal cells to the underlying basal lamina. We
      have shown that these hemidesmosomal complexes are lost in prostate carcinoma,
      possibly allowing malignant cells to detach from the anchoring structures and
      then to invade and migrate through the adjacent tissue. Our previous
      immunohistochemical studies of normal and malignant human prostate tissue
      demonstrated that the laminin subchains alpha 1, alpha 2, beta 1, beta 2, gamma
      1, and gamma 2 were all expressed as normal components of the basal lamina
      surrounding prostate glands. Although most of these subchains were also expressed
      by the de novo basal lamina synthesized by prostate carcinoma, the gamma 2
      subchain of laminin 5 was not detected. In an effort to investigate the role
      laminin 5 plays in the tumorigenesis of prostate carcinoma, the protein
      expression of the three subchains of laminin 5 (alpha 3, beta 3, and gamma 2) was
      compared in normal prostate, prostatic intraepithelial neoplasia, and invasive
      carcinoma using immunohistochemistry. The results showed that the protein for the
      alpha 3 subchain of laminin 5 is retained by both normal prostate epithelium and
      prostate carcinoma, but the beta 3 and the gamma 2 subchains were not detected in
      invasive carcinoma. Despite the absence of the gamma 2 protein, however, the
      carcinoma cells continued to express substantial amounts of the gamma 2 mRNA.
      Although it is unclear how the gene for the gamma 2 subchain of laminin 5 is
      regulated, results of this study suggest that there is a post-transcriptional
      defect in the expression of the gamma 2 subchain that occurs during the
      progression from a premalignant lesion to invasive carcinoma. As laminin 5 is a
      component of the anchoring filaments, the failure to express the gamma 2 subchain
      may contribute to the failure to form anchoring filaments and hemidesmosomes.
      This failure of hemidesmosome formation results in a less stable epithelial
      stromal junction, which may allow malignant cells more potential to invade and
      spread through adjacent structures.

PMID- 8863682
TI  - Poor correlation between clonal immunoglobulin gene rearrangement and
      immunoglobulin gene transcription in Hodgkin's disease.
AB  - It recently has been suggested that some cases of Hodgkin's disease (HD) are
      derived from B lymphocytes. We therefore examined immunoglobulin heavy chain gene
      rearrangement and transcription by polymerase chain reaction in 30 cases of HD
      and compared them with 25 cases of non-Hodgkin's B-cell lymphoma. Clonal VDJ gene
      rearrangements were observed in 6 cases of HD. Of these 6 cases, clonal VDJ gene
      transcription was found by RNA-dependent polymerase chain reaction in only 2
      cases. One of these 2 cases histologically showed composite lymphoma of HD and
      diffuse large B cell lymphoma. We performed in situ hybridization with a clonal
      VDJ gene probe in this case to determine the localization of the genetic
      clonality. The large lymphoma cells reacted positively, but Hodgkin's and Reed
      Sternberg cells showed only nonspecific staining. No discrepancy between
      immunoglobulin gene rearrangement and transcription was observed in 24 of the 25
      cases of non-Hodgkin's B-cell lymphoma. The discordance between clonal gene
      rearrangement and transcription in HD contrasts sharply with the high correlation
      of those processes in non-Hodgkin's B-cell lymphoma.

PMID- 8863683
TI  - Detection of Kaposi's sarcoma-associated herpesvirus-like DNA sequence in
      angiosarcoma.
AB  - The partial DNA sequence of a putative new herpesvirus has recently been isolated
      from almost all cases of Kaposi's sarcoma (KS), from a small subset of AIDS
      related lymphomas, and from a high proportion of multicentric Castleman's
      disease. The presence of this KS-associated herpesvirus, which is also known as
      human herpes virus 8 (KSHV/ HHV8), has not been reported in vascular tumors other
      than KS. We therefore examined a series of vascular neoplasms of both endothelial
      and pericyte derivation using polymerase chain reaction to detect a 233-hp
      segment of the viral DNA. KSHV/HHV8 sequences were found in 7 of 24 (29%)
      angiosarcomas and 1 of 20 (5%) hemangiomas but not in any hemangiopericytomas (0
      of 6). The presence of the virus in angiosarcoma was confirmed by direct
      sequencing of the polymerase chain reaction product and Southern blotting in one
      case each. Only one of the affected patients was known to be immunocompromised.
      By detecting its presence in a significant proportion of angiosarcomas, this
      study extends the number of tumors associated with KSHV/HHV8, further tightens
      its association with malignancy, and suggests a tropism of the virus for
      endothelial cells. The presence of KSHV/HHV8 in angiosarcomas in addition to
      classical KS also indicates that immunosuppression is not a requisite for viral
      infection.

PMID- 8863684
TI  - Biochemical and morphological characterization of vascular and lymphocytic
      interleukin-4 receptors.
AB  - The distribution of the interleukin (IL)-4 receptor in normal human and common
      marmoset (Callithrix jacchus) tissues was examined by immunofluorescence and flow
      cytometry using monoclonal antibodies specific for the human IL-4 receptor to
      gain further insight into IL-4-mediated inflammatory and immunological events. IL
      4 receptor positivity was unequivocally demonstrated on lymphocytes,
      predominantly T cells, and on blood vessels in many tissues. Vascular IL-4
      receptor immunofluorescence consisted of a strong smooth muscle cell positivity
      and weaker positive staining of capillary and venular endothelial cells.
      Subnanomolar concentrations of IL-4 induced a genistein-sensitive up-regulation
      of VCAM-1 in vascular cell cultures. Tumor necrosis factor-alpha induced a
      genistein-resistant up-regulation of VCAM-1. IL-4 strongly induced expression of
      the IL-4 receptor on splenocytes (T lymphocytes) but not on vascular smooth
      muscle or endothelial cell cultures. Receptor cross-linking to [125I]IL-4
      revealed a 65- to 75-kDa accessory receptor subunit consistent with a recently
      cloned IL-13 receptor associated with the IL-4 receptor on both vascular
      endothelial and smooth muscle cells. The demonstration of a vascular distribution
      pattern for the IL-4 receptor in addition to expression on lymphocytes suggests
      that vascular functional alterations, transduced through a unique IL-4 receptor
      complex (the type II IL-4 receptor), may be of importance during immunological
      and allergic inflammatory events.

PMID- 8863685
TI  - DNA fragmentation in mouse organs during endotoxic shock.
AB  - The systemic inflammatory response syndrome has still an unpredictable outcome,
      and patients often die of multiple organ failure despite circulatory
      stabilization therapy. The still incompletely understood pathophysiological
      mechanisms include organ damage due to direct toxic actions of cytokines elicited
      by overactivation of the host response. To study this process of organ failure in
      experimental septic shock, we injected mice with a lethal dose of endotoxin and
      examined apoptotic and necrotic tissue damage biochemically, histologically, and
      ultrastructurally. Endotoxin administration caused oligonucleosomal as well as
      random DNA fragmentation in liver, lung, kidney, and intestine. In the liver, DNA
      fragmentation was not restricted to hepatocytes but also occurred in
      nonparenchymal cells. The DNA fragmentation was mediated by tumor necrosis factor
      and attenuated by endogenous nitric oxide release. Unlike the situation in D
      galactosamine-sensitized mice, in which injection or release of tumor necrosis
      factor causes massive hepatocyte apoptosis, liver failure due to high doses of
      endotoxin was characterized by single-cell necrosis, a low incidence of
      apoptosis, and simultaneous damage to nonparenchymal cells. We conclude that,
      even though endotoxin causes cytokine-mediated DNA fragmentation in several
      organs including the liver, hepatocyte apoptosis itself seems to be a minor
      phenomenon in high-dose endotoxic shock in mice.

PMID- 8863686
TI  - Adenoviral gene transfer of macrophage inflammatory protein-2 in rat lung.
AB  - Replication-defective adenoviral vectors are capable of localized transfer and
      expression of incorporated gene product in lung tissue. We have constructed an
      adenoviral vector that expresses rat macrophage inflammatory protein (MIP)-2, a C
      X-C chemokine specifically chemotactic for neutrophils, Supernatants from 293
      cells, infected with the adenoviral MIP-2 (ADMIP-2) construct, showed potent
      chemotactic activity and the ability of the ADMIP-2 vector to transcribe and make
      functional protein was confirmed. In vivo analysis of bronchoalveolar lavage
      fluid from rats after intratracheal instillation of ADMIP-2 (10(9) plaque-forming
      units) showed a 10-fold increase in the absolute number of neutrophils in
      bronchoalveolar lavage fluid as opposed to rats treated with an equal titer of an
      E1-disabled control virus expressing firefly luciferase (ADCA-18). Neutrophils
      constituted 65% of total BAL cells with alveolar macrophages being the other
      major cell type recovered. Rat MIP-2 protein was increased (nanograms per
      milliliter) in bronchoalveolar lavage fluid over a period of 7 days in ADMIP-2
      treated animals. MIP-2 mRNA was demonstrated by Northern blot analysis in lung
      tissue, and histological analysis confirmed the presence of massive localized
      tissue neutrophilia. Evidence of chronic tissue injury and repair (ie, fibrosis)
      was not detected up to 2 weeks after the neutrophil infiltrate had resolved,
      subsequent to decreased chemokine presence. Adenoviral gene transfer proved an
      effective tool for the assessment of lung tissue expression of this chemokine in
      vivo and is useful in developing rodent models of tissue neutrophilia.

PMID- 8863687
TI  - Elastin and collagen remodeling in emphysema. A scanning electron microscopy
      study.
AB  - The relationship between elastin degradation and emphysema is well known. Recent
      evidence suggests that a complex process of pulmonary remodeling occurs within
      the emphysematous lung. The aim of this study was to assess the extent of
      extracellular matrix remodeling in emphysema by ultrastructural examination of
      elastin and collagen templates in an animal model of emphysema and in human
      emphysematous lungs. Emphysema was induced in rats by the intratracheal
      administration of porcine pancreatic elastase. Human lung samples were obtained
      at surgical resection for lung carcinoma. Emphysema was confirmed
      morphometrically and quantitated using the mean linear intercept. Matching
      sections were treated with sodium hydroxide and formic acid to expose collagen
      and elastin templates, respectively. Scanning electron microscopy with stereo
      pair imaging allowed three-dimensional visualization of the exposed templates. In
      emphysematous lungs from both sources, sheets of elastin were disrupted and
      perforated with multiple fenestrations. In elastase-induced emphysema, this
      disintegration was accompanied by a marked increase in thickness of collagen
      fibrils, which contrasted with the fine fibrillar network of control lungs.
      Similarly, a pattern of thickened fibrils and disorganized deposition of collagen
      was observed in human lungs. In conclusion, these findings support the novel
      concept of increased collagen deposition and aberrant collagen remodeling in the
      pathogenesis of emphysema.

PMID- 8863688
TI  - Bracken fern-induced bladder tumors in guinea pigs. A model for human neoplasia.

PMID- 8863690
TI  - The case against new reproductive technologies in developing countries.

PMID- 8863691
TI  - The choice of luteal support following pituitary down regulation, controlled
      ovarian hyperstimulation and in vitro fertilisation.

PMID- 8863689
TI  - Inhibins and activins: roles in clinical practice.

PMID- 8863692
TI  - William Hewson and the lady without the coagulable lymph.

PMID- 8863693
TI  - Lack of analgesic effect of systemically administered morphine or pethidine on
      labour pain.
AB  - OBJECTIVE: To evaluate the true analgesic effect of morphine and pethidine on
      labour pain. DESIGN: The analgesic and sedative effects of intravenous morphine
      or pethidine and their effect on anxiety were compared in a prospective, double
      blind, randomised dose-response study. SETTING: A Stockholm teaching hospital
      obstetric unit. PARTICIPANTS: Ten healthy nulliparous parturients in active
      labour were included in each group. RESULTS: Even after repeated doses (up to
      0.15 mg/kg body weight morphine and up to 1.5 mg/kg body weight pethidine) the
      findings were uniform, with very high pain scores maintained in each group as
      assessed with visual analogue scale. The parturients were all significantly
      sedated and several fell asleep but were awakened by pain during contractions.
      CONCLUSION: It is concluded that labour pain is not sensitive to systemically
      administered morphine or pethidine. These drugs only cause heavy sedation. It
      therefore seems unethical and medically incorrect to meet parturients' requests
      for pain relief by giving them sedation. Considering the well documented negative
      effects on newborn infants we also believe systemic pethidine should be avoided
      in labour.

PMID- 8863695
TI  - A comparison of the inactive urinary kallikrein:creatinine ratio and the
      angiotensin sensitivity test for the prediction of pre-eclampsia.
AB  - OBJECTIVE: To determine the relation between the inactive urinary kallikrein:
      creatinine ratio (IUK:Cr) and the angiotensin sensitivity test (AST) at 28 weeks
      of gestation and to assess each as a screening test for pre-eclampsia. DESIGN:
      Prospective interventional study. SUBJECTS: Four hundred and fifty-nine
      normotensive nulliparous women recruited from hospital antenatal clinics.
      SETTING: John Radcliffe Maternity Hospital, Oxford, and Queen Charlotte's and
      Chelsea Hospital, London. INTERVENTIONS: A urine sample for IUK:Cr measurement
      was provided before performing the AST at 28 weeks of gestation. Those women who
      demonstrated increased sensitivity to angiotensin II were entered into a
      randomised placebo controlled trial of low dose aspirin for the prevention of pre
      eclampsia (CLASP). MAIN OUTCOME MEASURES: The development of pre-eclampsia.
      RESULTS: The IUK:Cr ratio was significantly lower in those women who showed
      increased sensitivity to angiotensin II (P < 0.0001 Student's t test). The
      sensitivity and specificity for detecting pre-eclampsia were, respectively, 22%
      and 85% for the AST and 67% and 75% for the IUK:Cr. Low-dose aspirin (60 mg) had
      no effect on the pregnancy outcome. CONCLUSION: There appears to be some relation
      between the IUK:Cr and AST tests in pregnancy. However, in this population, the
      IUK:Cr ratio was a better screening test for pre-eclampsia than the AST, but
      overall neither test was a powerful predictor for the syndrome.

PMID- 8863694
TI  - Maternal mortality in England and Wales 1970-1985: an analysis by country of
      birth.
AB  - OBJECTIVE: To determine the risk of maternal mortality in immigrants to England
      and Wales. DESIGN: Analysis of death registrations, 1970-1985, by country of
      birth. SETTING: England and Wales. POPULATION: Women dying in England and Wales
      during pregnancy, childbirth or the puerperium, or dying from malignant tumour of
      the placenta. MAIN OUTCOME MEASURES: The risk of dying in pregnancy, childbirth
      or the puerperium, adjusted for age and year of death, and the risk of cause
      specific death, adjusted for age, in immigrants compared with women born in
      England and Wales. RESULTS: Women born in West Africa (relative risk 10.3; 95% CI
      8.0-13.2) and the Caribbean (4.6; 3.8-5.7) were at very elevated risk of maternal
      death and of the main causes of death. Women from Southern Asia (1.6; 1.3-2.0)
      and "Europe and the USSR' (1.7; 1.2-2.3) were at moderate risk. Adjustment for
      year of death increased the estimates of risk and women born in the "Rest of the
      World' and Scotland were at significantly elevated risk. CONCLUSIONS: An
      increased incidence of obstetric conditions in immigrant groups may account for
      the elevated risk but it is also possible that differences in care may account
      for some of the additional risk. The pattern of increased risk does not appear to
      be explicable by the parity or social class distribution of immigrants as far as
      data are available on these. Research is required into the aetiology of the
      differential incidence of obstetric disease. The collection of routine mortality
      data which include maternal reproductive and social factors would elucidate the
      significance of such factors to maternal health. Further investigation into
      possible differences in the process of antenatal care between immigrants and non
      immigrants is required, and into whether this affects the risk of maternal
      mortality.

PMID- 8863696
TI  - Changes in maternal heart dimensions and plasma atrial natriuretic peptide levels
      in the early puerperium of normal and pre-eclamptic pregnancies.
AB  - OBJECTIVE: To measure plasma atrial natriuretic peptide (ANP) in relation to
      maternal haemodynamics and body fluid balance in the early puerperium following
      uncomplicated pregnancy and pre-eclampsia. DESIGN: A longitudinal study from late
      pregnancy and into the early postpartum period (days 1 to 3 and days 4 to 6)
      compared with nonpregnant controls. SUBJECTS: Eleven women with uncomplicated
      pregnancies, 12 women with pre-eclampsia and 12 healthy, nonpregnant women. MAIN
      OUTCOME MEASURES: Maternal heart dimensions determined by M-mode
      echocardiography, concentrations of ANP, and daily urine output and sodium
      excretion. RESULTS: After delivery increases in left atrial dimensions,
      represented as mean (SEM), from 33.2 (1.6) to 37.7 (1.7) mm and ANP levels from
      7.9 (1.1) to 19.0 (2.7) pmol/L were observed at 1-3 days postpartum in normal
      pregnant women, but we were not able to demonstrate a significant increase in
      diuresis and natriuresis. In the third trimester left atrial dimensions (38.4
      (1.2) mm) and ANP levels (15.4 (2.2) pmol/L) were greater in pre-eclampsia. ANP
      levels rose further in pre-eclamptic women in the early puerperium (27.4 (7.4)
      pmol/L) with an increase in diuresis and natriuresis, while left atrial
      dimensions did not change significantly (39.4 (1.7) mm). A pericardial effusion
      was found in 11 pre-eclamptic but in only three healthy pregnant women.
      CONCLUSIONS: A concommitant increase in left atrial dimensions and ANP in the
      early puerperium following uncomplicated pregnancies is consistent with the
      mechanism of atrial stretch as a stimulus for ANP release, although the
      biological significance of this finding remained unclear. A significantly higher
      release of ANP in the early puerperium after pregnancies complicated by pre
      eclampsia may be a mechanism which promotes the renal elimination of excessive
      body fluids and sodium.

PMID- 8863697
TI  - Peak systolic over protodiastolic ratio as an objective substitute for the
      uterine artery notch.
AB  - OBJECTIVE: To measure the inter-rater agreement for the identification of a
      uterine artery notch, as well as the association between an observed notch and
      the peak systolic over protodiastolic (A/C) ratio. DESIGN: Cohort study. SETTING:
      Tertiary care university hospital. POPULATION AND METHODS: Six hundred and sixty
      five nulliparous women in whom 1022 examinations of uterine artery velocity
      waveforms were performed by pulsed Doppler at 18 and at 26 weeks of gestation.
      Agreement between two independent raters was analysed using Cohen's kappa
      statistics. A/C ratios of flow velocity waveforms with or without a notch were
      compared. The agreement between A/C values and the presence of a notch was
      estimated by measuring the surface under the receiver operating characteristic
      (ROC) curve. RESULTS: Inter-rater agreement for the identification of a notch was
      0.74 (95% CI 0.64-0.83) at 18 weeks and 0.72 (95% CI 0.64-0.80) at 26 weeks. A/C
      ratios were higher when a notch was present (P < 0.0001). The area under the ROC
      curve was 0.86 (95% CI 0.81-0.91) for the placental uterine artery and 0.93 (95%
      CI 0.90-0.96) for the nonplacental artery. An A/C value > or = 2.5 in any uterine
      artery had a sensitivity of 88% and a specificity of 86% to detect a notch.
      CONCLUSION: Although there is no definitive definition of the notch, its
      detection is reproducible within a center. However, published prevalences between
      centers in unselected populations vary. The measure of the A/C ratio can serve as
      an objective substitute.

PMID- 8863698
TI  - Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal
      translucency thickness at 10-14 weeks of gestation.
AB  - OBJECTIVE: To determine the prevalence of increased fetal nuchal translucency
      thickness in twin pregnancies and to evaluate screening for trisomy 21 by a
      combination of translucency thickness and maternal age. DESIGN: Prospective
      screening study at 10 to 14 weeks of gestation. SETTING: Fetal Medicine Centre.
      POPULATION: 22,518 self-selected pregnant women at 10 to 14 weeks of gestation,
      including 21,477 singleton and 448 twin pregnancies with live fetuses. METHODS:
      Fetal nuchal translucency thickness was measured by ultrasound examination at 10
      14 weeks. Sensitivity and false positive rates of screening for trisomy 21 by a
      combination of fetal nuchal translucency thickness and maternal age were
      calculated. MAIN OUTCOME MEASURES: Prevalence of increased nuchal translucency
      thickness and detection of trisomy 21. RESULTS: In the 448 twin pregnancies the
      nuchal translucency thickness was above the 95th centile of the normal range (for
      crown-rump length in singletons) in 65/896 fetuses (7.3%), including 7/8 (88%)
      with trisomy 21. Increased translucency was also present in four fetuses with
      other chromosomal abnormalities. In the chromosomally normal twin pregnancies the
      prevalence of increased nuchal translucency was higher in fetuses from
      monochorionic (8.4%; 16/190) than in those with dichorionic pregnancies (5.4%;
      37/688). The minimum estimated risk for trisomy 21, based on maternal age and
      fetal nuchal translucency thickness, was 1 in 300 in 19.5% (175/896) of the twins
      including all eight of those with trisomy 21. CONCLUSIONS: In twin pregnancies
      the sensitivity of fetal nuchal translucency thickness in screening for trisomy
      21 is similar to that in singleton pregnancies, but the specificity is lower
      because translucency is also increased in chromosomally normal monochorionic twin
      pregnancies.

PMID- 8863699
TI  - Application of ultrasonic transit time flowmetry to the measurement of umbilical
      vein blood flow at caesarean section.
AB  - OBJECTIVES: To determine the applicability of ultrasonic transit time flowmetry
      to the measurement at caesarean section of umbilical vein blood flow rate and to
      examine the relationship between flow rates and birthweight for gestational age.
      DESIGN: Umbilical vein blood flow was measured at caesarean section using a
      transonic time flow probe on a loop of the umbilical cord in 33 appropriate and
      21 small for gestational age fetuses. RESULTS: The mean (SD) umbilical vein blood
      flow in the 54 fetuses was 78.4 (23.1) ml kg-1 min-1. There was a linear relation
      between umbilical vein blood flow measured by ultrasonic transit time flowmetry
      and birthweight (r = 0.63, P < 0.0001). The mean umbilical vein blood flow in
      appropriate for gestational age fetuses [90 (18) ml kg-1 min-1] was greater than
      that in the small for gestational age group [66 (23) ml kg-1 min-1], P < 0.04).
      CONCLUSIONS: Umbilical vein blood flow measurements obtained by the ultrasonic
      transit time flowmetry technique are simple to perform and compare well with
      reported values obtained by the Doppler ultrasound technique (when vessel
      diameter is greater than 4 mm). Umbilical venous blood flow rate is significantly
      lower in small for gestational age fetuses.

PMID- 8863700
TI  - Serum parameters and nuchal translucency in first trimester screening for fetal
      chromosomal abnormalities.
AB  - OBJECTIVE: To assess the relation between serum parameters and nuchal
      translucency in pregnancies affected by fetal aneuploidy in the first trimester.
      DESIGN: Retrospective study of different serum parameters collected prior to
      chorionic villus sampling and measurement of nuchal translucency in relation to
      fetal aneuploidy. SETTING: Switzerland (German and Italian sector) and Bregenz,
      Austria. POPULATION: One thousand one hundred and fifty-one women aged 25 to 44
      years at 10 to 13 weeks of gestation undergoing chorionic villus sampling, mostly
      for advanced maternal age. Fetal aneuploidy was found in 23 pregnancies including
      four cases of trisomy 21, five of trisomy 18 and one case of trisomy 13. MAIN
      OUTCOME MEASURE: Fetal karyotype, serum levels of free beta-hCG, pregnancy
      associated plasma protein A (PAPP-A) and alpha-fetoprotein and the measurement of
      nuchal translucency. RESULTS: Serum PAPP-A was decreased in all common
      chromosomal abnormalities. Free beta-hCG levels were increased in trisomy 21 but
      decreased in trisomy 18, whereas alpha-fetoprotein was low in trisomy 21, 18 and
      other chromosomal abnormalities. Nine of twenty-three abnormal embryos had
      evidence of an increased nuchal translucency. Nuchal translucency, however, did
      not seem to be associated with any alteration in the levels of the biochemical
      parameters in either chromosomally normal or abnormal embryos. A low serum PAPP-A
      or an increased nuchal translucency was seen in two-thirds of all pregnancies
      with chromosomal abnormalities. CONCLUSION: A nuchal translucency > or = 3 mm and
      depressed serum PAPP-A levels have a good predictive value in the detection of
      fetal aneuploidy at 10 to 13 weeks of pregnancy. Serum free beta-hCG and alpha
      fetoprotein levels may give additional information. An increased nuchal
      translucency was not associated with altered serum parameters. This would allow
      these different markers to be used in combination.

PMID- 8863701
TI  - Estimation of fetal lung volume using enhanced 3-dimensional ultrasound: a new
      method and first result.
AB  - OBJECTIVE: To measure fetal lung volume using a computer based, enhanced, 3
      dimensional ultrasound imaging system. DESIGN: An observational study. SETTING:
      The Fetal Medicine Unit at Guys Hospital, London. PARTICIPANTS: Twenty healthy
      women with a singleton pregnancy between 24 and 36 weeks of gestation were
      scanned on one occasion during pregnancy using an ultrasound based 3-dimensional
      imaging system. All delivered at term with weights above the 10th centile for
      gestation. RESULTS: Total lung volume increased exponentially with gestational
      age. Right lung volume measured consistently greater than left lung volume.
      CONCLUSIONS: The use of this new enhanced 3-dimensional imaging system allows for
      estimations of fetal lung volume. Preliminary data confirm that fetal lung
      volume, measured by a computerised 3-dimensional ultrasound imaging system
      increased exponentially with gestational age. The use of this system has obvious
      application in the further study of lung growth in utero and possible clinical
      application in disease states where fetal lung growth may be impaired.

PMID- 8863702
TI  - Persistent ectopic pregnancy following conservative surgery for tubal pregnancy.
AB  - OBJECTIVE: To audit the incidence and management of persistent ectopic pregnancy
      following conservative tubal surgery performed at laparotomy and via the
      laparoscope. DESIGN: A retrospective analysis of the case records. SETTING: The
      Birmingham and Midland Hospital for Women. PARTICIPANTS: Two hundred and fourteen
      women who received surgical treatment for ectopic pregnancy between October 1991
      and December 1994. RESULTS: Of the 85 women who underwent conservative tubal
      surgery, nine were diagnosed as having persistent ectopic pregnancy on the basis
      of hCG values. The incidence after laparoscopy was no higher than after
      laparotomy. A second surgical procedure was indicated in only four cases.
      CONCLUSIONS: Post-operative surveillance of serum hCG remains mandatory. Patients
      who remain symptom free may be managed conservatively The threshold for a second
      look laparoscopy should be relatively high and be based on the presence of
      symptoms rather than changes in hCG values.

PMID- 8863703
TI  - A population based survey of women's experience of the menopause.
AB  - OBJECTIVES: To describe the prevalence of, and degree of distress caused by, 15
      symptoms commonly attributed to the menopause among a random sample of women aged
      45 to 54, selected from the total population of a geographically defined area.
      DESIGN: Postal questionnaire survey. SETTING: Grampian Health Board area.
      PARTICIPANTS: Eight thousand women, aged 45 to 54, randomly selected from the
      Grampian Community Health Index. MAIN OUTCOME MEASURES: Self-reported symptoms,
      including depression, and use of hormone replacement therapy (HRT) among women of
      differing menopausal status. RESULTS: The response rate was 78%; 57% of
      respondents had experienced one or more of the 15 symptoms listed, but only 22%
      had found such symptoms a problem. Women's experience of classic vasomotor and
      atrophic symptoms varied according to menopausal status but experience of general
      somatic and psychological symptoms did not. Users of HRT and women whose
      menopause was iatrogenic found more symptoms a problem. CONCLUSIONS: Symptoms
      attributed to the menopause are common among women in the age group studied but
      often are not perceived as a problem. Among nonusers of HRT, only vasomotor and
      atrophic symptoms vary with menopausal status. Other somatic and psychological
      symptoms experienced by middle-aged women cannot be regarded as part of the same
      "menopausal syndrome'.

PMID- 8863704
TI  - A new method for measuring menstrual blood loss and its use in screening women
      before endometrial ablation.
AB  - OBJECTIVE: 1. To develop and validate a method for measuring menstrual blood loss
      in a routine setting, and 2. To assess the value of measuring menstrual blood
      loss before endometrial ablation. DESIGN: A prospective, observational study.
      SETTING: Four Yorkshire hospitals: The General Infirmary at Leeds, St. James's
      University Hospital, Leeds, St. Luke's Hospital, Bradford and The Friarage
      Hospital, Northallerton. PARTICIPANTS: Three hundred and seventy-two women who
      had been offered endometrial ablation for menorrhagia. MEASUREMENT: Sanitary
      material was washed with a nonionic detergent in a known volume of water. The
      haemoglobin in a sample of solution was measured by mixing with sodium carbonate
      for spectrophotometric analysis. INTERVENTIONS: The menstrual blood loss result
      was revealed to each women. Electrosurgical endometrial ablation was performed
      for those who decided to have surgery. MAIN OUTCOME MEASURES: Proportion of women
      with normal menstrual blood loss (< or = 80 mL) who avoided surgery. Comparison
      of endometrial ablation outcome in women with and without genuine menorrhagia.
      RESULTS: Thirty-six women (10%) with normal menstrual blood loss who declined
      surgery continued to avoid surgery after a mean of 27 months. Two hundred and
      ninety-two women were followed up for one year after endometrial ablation. Those
      with genuine menorrhagia (n = 122) were less likely to be dissatisfied (9% vs
      18%) (OR 2.5, 95% CI 1.1-4.7) or to require hysterectomy (4% vs 7%) (OR 1.8, 95%
      CI 0.6-5.2) than women with normal menstrual blood loss (n = 170). CONCLUSIONS:
      The objective diagnosis of menorrhagia can be undertaken in a routine setting and
      may provide some women, who have a normal menstrual blood loss, sufficient
      reassurance to refrain from surgery. Women with genuine menorrhagia have a better
      outcome after endometrial ablation than those with normal menstrual blood loss.

PMID- 8863705
TI  - Anal and urinary incontinence in women with obstetric anal sphincter rupture.
AB  - OBJECTIVE: To assess the long term impact of obstetric anal sphincter rupture on
      the frequency of anal and urinary incontinence and to identify factors to predict
      women at risk. DESIGN: An observational study. SETTINGS: Departments of
      Obstetrics and Gynaecology and of Surgery D, Glostrup County University Hospital,
      Denmark. PARTICIPANTS: Ninety-four consecutive women who had sustained an
      obstetric anal sphincter rupture. INTERVENTIONS: Assessment of history, anal
      manometry, anal sphincter electromyography and pudendal nerve terminal motor
      latency at three months postpartum A questionnaire regarding anal and urinary
      incontinence was sent two to four years postpartum. MAIN OUTCOME MEASURES: The
      frequency of anal and urinary incontinence and risk factors for the development
      of incontinence. RESULTS: Thirty of 72 women (42%) who responded had anal
      incontinence two to four years postpartum; 23 (32%) had urinary incontinence and
      13 (18%) had both urinary and anal incontinence. Overall, 40 of 72 women (56%)
      had incontinence symptoms. The occurrence of anal incontinence was associated
      with pudendal nerve terminal motor latencies of more than 2.0 ms, and the
      occurrence of urinary incontinence was associated with the degree of rupture, the
      use of vacuum extraction and previous presence of urinary incontinence. Seventeen
      women had subsequently undergone a vaginal delivery in relation to which four
      (24%) had aggravation of anal incontinence, and three (18%) had aggravation of
      urinary incontinence. Of the women with incontinence, 38% wanted treatment but
      only a few had sought medical advice. CONCLUSIONS: Obstetric anal sphincter
      rupture is associated with a risk of approximately 50% for developing either anal
      or urinary incontinence or both. The prediction of women at risk is difficult.
      Information and routine follow up of all women with obstetric anal sphincter
      rupture is mandatory.

PMID- 8863706
TI  - Maternal phenylketonuria 1987 to 1993, pregnancy outcome and early infant
      development: the Northern Ireland experience.

PMID- 8863707
TI  - Nuchal translucency: a marker for the antenatal diagnosis of aortic coarctation.

PMID- 8863708
TI  - Mycobacterium fortuitum infection of the endometrium: a rare cause of
      infertility.

PMID- 8863709
TI  - Small bowel injury in gastroschisis: relation to fetal presentation.

PMID- 8863710
TI  - Assessing the costs of assisted reproductive techniques.

PMID- 8863711
TI  - Assessing the costs of assisted reproductive techniques.

PMID- 8863712
TI  - Induction of labour: a randomised clinical trial of amniotomy versus amniotomy
      with oxytocin infusion.

PMID- 8863713
TI  - The Burch colposuspension for women with and without detrusor overactivity.

PMID- 8863714
TI  - Transcervical analgesia for laparoscopic sterilisation.

PMID- 8863715
TI  - Screening for fetal trisomies by maternal age and fetal nuchal translucency
      thickness at 10 to 14 weeks of gestation.

PMID- 8863716
TI  - On the association between maternal phosphoglucomutase 1 (PGM1) and fetal
      macrosomia in diabetic pregnancy.

PMID- 8863717
TI  - Intrapartum fetal cerebral near infrared spectroscopy: apparent change in
      oxygenation demonstrated in a nonviable fetus. University of London Near Infrared
      Spectroscopy Group.

PMID- 8863718
TI  - Screening of fetal trisomies by maternal age and fetal nuchal translucency
      thickness at 10 to 14 weeks of gestation.

PMID- 8863719
TI  - Chorioamnionitis due to Pseudomonas aeruginosa: a complication of prolonged
      antibiotic therapy for premature rupture of membranes.

PMID- 8863720
TI  - Chorioamnionitis due to Pseudomonas aeruginosa: a complication of prolonged
      antibiotic therapy for premature rupture of membranes.

PMID- 8863721
TI  - Twin to twin blood transfusion in a dichorionic pregnancy without the
      oligohydramnios-polyhydramnios sequence.

PMID- 8863722
TI  - Molecular cloning of Quek 1 and 2, two quail vascular endothelial growth factor
      (VEGF) receptor-like molecules.
AB  - We have previously reported the cloning of two partial cDNAs corresponding to two
      quail (Coturnix coturnix japonica) receptor tyrosine kinases (RTKs), named Quek 1
      and Quek 2, and their expression in endothelial cells of the early avian embryo.
      We here report the cloning of the full-size cDNAs for both molecules. Sequence
      comparison shows that Quek 1 and 2 share an overall amino acid (aa) identity of
      49%. They both comprise seven extracellular immunoglobulin-like (Ig-like)
      domains, a single transmembrane domain, and an intracellular kinase domain split
      into two by a 70 aa insertion. These structural characteristics are shared by the
      members of the recently discovered VEGF receptor (VEGFR) family. We have compared
      the sequences of Quek 1 and 2 to the other VEGFRs. At the aa level, Quek 1 is
      most closely related to KDR/flk-1 (VEGFR 2) (aa identity of 69% and 71%,
      respectively). Quek 2 shows a similar degree of aa identity to fit-4 (VEGFR 3).
      Quek 1 and 2 display a lower homology to fit-1 (VEGFR 1) (about 45% aa identity).
      These data suggest that Quek 1 and 2 are the avian homologues of VEGFRs 2 and 3,
      respectively.

PMID- 8863723
TI  - The LTR, v-src, LTR provirus in H-19 hamster tumor cell line is integrated
      adjacent to the negative regulatory region.
AB  - The tumor hamster cell line H-19 harbors a single copy LTR, v-src, LTR provirus
      that becomes permanently transcriptionally suppressed in morphological revertants
      segregating at high rate from this cell line. Our previous data document that the
      provirus suppression is mediated by epigenetic cell-regulatory mechanisms. In
      this report, we concentrate on cellular sequences neighboring the integration
      site. The locus is unique for Syrian hamster and is not detectable in DNA of
      several animal species. No restriction sites that usually hint at the presence of
      CpG islands were found in the significantly close vicinity of the provirus.
      Nevertheless, the chromosomal DNA flanking the provirus is rich in GC content
      (57.8%). We localized a 0.5-kb region downstream from the provirus that
      remarkably inhibits transcription in the transient expression assay and is
      effective both on the homologous RSV LTR promoter/enhancer and heterologous SV40
      promoter. We propose that a cellular trans-acting factor is involved in the
      silencing of the reporter gene. Since this activity is comparable both in
      transformed and revertant cells, we speculate that this down-regulatory region
      makes the permissive integration locus prone to provirus silencing initiated by
      other fluctuating stimuli.

PMID- 8863724
TI  - Trypanosoma cruzi elongation factor 1-alpha: nuclear localization in parasites
      undergoing apoptosis.
AB  - The cloning and sequencing of the gene coding for Trypanosoma cruzi elongation
      factor 1 alpha (TcEF-1 alpha) was performed by screening a T. cruzi genomic
      library with a probe obtained through the polymerase chain reaction (PCR)
      amplification of T. cruzi DNA using two oligonucleotides deduced from the
      sequence of T. brucei EF-1 alpha. Southern blot analysis of T. cruzi digested
      genomic DNA and Northern blot hybridized with the labeled probe revealed that one
      copy of TcEF-1 alpha exist in the genome of the parasite. Indirect
      immunofluorescence technique using anti-EF-1 alpha antibodies and epimastigotes
      harvested after different days of in vitro culture showed that EF-1 alpha is
      localised in the cytoplasm of the parasites from the exponential growth phase.
      Surprisingly, during the stationary phase (ageing parasites), EF-1 alpha was
      found in the nucleus. Furthermore, treatment of parasites with the antibiotic
      drug geneticin (G418) which induces the death of epimastigotes by apoptosis
      showed selective localization of EF-1 alpha in the nucleus of dying parasites.
      This observation supports the notion already reported in the case of mammalian
      cells that EF-1 alpha could participate in the transcription processes and
      possibly in the case of T. cruzi, in the expression regulation of genes involved
      in the control of cell death. The possible transfection and genomic manipulation
      of T. cruzi may provide a model to study the role of TcEF-1 alpha in this
      phenomenon.

PMID- 8863725
TI  - Structure of the rabbit kappa-casein encoding gene: expression of the cloned gene
      in the mammary gland of transgenic mice.
AB  - The rabbit kappa-casein (kappa-Cas) encoding gene has been isolated as a series
      of overlapping DNA fragments cloned from a rabbit genomic library constructed in
      bacteriophage lambda EMBL3. The clones harboured the 7.5-kb gene flanked by about
      2.1 kb upstream and 9 kb downstream sequences. The cloned gene is the most
      frequently occurring of two kappa-Cas alleles identified in New Zealand rabbits.
      Comparison of the corresponding domains in rabbit and bovine kappa-Cas shows that
      both genes comprise 5 exons and that the exon/intron boundary positions are
      conserved whereas the introns have diverged considerably. The first three introns
      are shorter in the rabbit, the second intron showing the greatest difference
      between the two species: 1.35 kb instead of 5.8 kb in the bovine gene. Repetitive
      sequence motives reminiscent of the rabbit C type repeat and the complementary
      inverted C type repeat were identified in the fourth and first introns,
      respectively. Transgenic mice were produced by microinjecting into mouse oocytes
      an isolated genomic DNA fragment which contained the entire kappa-Cas coding
      region, together with 2.1-kb 5' and 4.0-kb 3' flanking region. Expression of
      transgene rabbit kappa-Cas mRNA could be detected in the mammary gland of
      lactating transgenic mice and the production of rabbit kappa-Cas was detected in
      milk using species-specific antibodies. The cloned gene is thus functional.

PMID- 8863726
TI  - Genes for murine Y1 and Y3 Ro RNAs have class 3 RNA polymerase III promoter
      structures and are unlinked on mouse chromosome 6.
AB  - Murine YRNAs, which are components of the conserved Ro ribonucleoprotein (RNP)
      complex, have been identified by enzymatic RNA sequencing. Mouse Y1 (mY1) and Y3
      (mY3; originally named mY2) RNAs share 97 and 95% identity to the human Y1 and Y3
      RNAs, respectively. TATA-like sequences, Proximal Sequence Elements, and octamer
      sequences, which are upstream promoter element motifs indicative of Class 3 RNA
      Polymerase III (RNAPIII) transcribed genes, are found upstream of both the
      putative mY1 and mY3 coding regions. Further, these elements are strikingly
      conserved both in sequence and position relative to known Class 3 genes and to
      human YRNA genes. Inhibition of transcription in vitro by 200 micrograms/ml but
      not 1 microgram/ml of alpha-amanitin indicates transcription of the mouse YRNA
      genes by RNAPIII. Southern blot of C57BL/6J and Mus spretus murine genomic DNA
      with mY1 and mY3 gene-specific probes suggests that these genes are single copy
      in the mouse genome. Finally, gene mapping with a (C57BL/6J x SPRET/Ei)F1 x
      SPRET/Ei mouse interspecific backcross DNA panel localizes the mY1 gene to the
      distal end of mouse chromosome 6, close to the motheaten (me) autoimmunity locus.
      The mY3 gene maps to the proximal end of mouse chromosome 6 very close to the T
      cell receptor beta locus, in a region homologous to human chromosome 7 where the
      human YRNA genes have been mapped.

PMID- 8863727
TI  - Genomic organization of the fungus Phycomyces.
AB  - The fungus Phycomyces blakesleeanus has a relatively small genome, 30 megabases
      (Mb), with a low guanine and cytosine (G + C) content, 35%; the coding sequences
      cloned to date all have a G + C content of about 50%. In order to investigate the
      organization of the genome of this fungus, we have cloned and sequenced 251 DNA
      fragments. One hundred and twenty-six clones were obtained by digestion with MspI
      (target sequence 5'-CCGG-3') and 125 random clones were obtained by sonication.
      The average length of sequence obtained was about 200 base pairs (bp) and the
      total length was about 50 kilobases (kb). The G + C content is not homogeneous
      throughout the genome: sequences obtained after digestion with MspI have an
      average of 5% more G + C content than the random fragments, and are enriched in
      coding sequences. Fourteen MspI fragments show similarities to known proteins and
      21 encode ribosomal RNA (rRNA). By contrast, only three of the random fragments
      are similar to known proteins and only one to a rRNA. We conclude that the
      Phycomyces genome is composed of G + C-rich genes surrounded by G + C-poor areas.
      Two clones have similarities to the transposase of the transposon Tc1 from
      Caenorhabditis elegans. This result suggests the presence of a high copy number
      of a Tc1-like transposable element in the Phycomyces genome. Another clone was
      similar to the transposon Tx1 from Xenopus laevis. A novel repetitive nt sequence
      has been characterized; about 5% of the total genome is a repetition of any of
      two consensus sequences of 31 bp named PrA1 and PrA2.

PMID- 8863728
TI  - Construction and expression of a synthetic wheat storage protein gene.
AB  - A synthetic wheat high-molecular-weight (HMW) glutenin storage protein gene
      analog was constructed for expression in E. coli. This first synthetic HMW
      glutenin gene and future modifications are intended to allow systematic
      dissection of the molecular basis of HMW-glutenin role in the visco-elastic
      properties critical for wheat product processing and utilization. The design of
      the gene included four features: different construction strategies for the
      separate assembly of major polypeptide domains, the inclusion of convenient
      restriction sites for modifications, use of a codon selection similar to E. coli
      highly expressed genes, and the ability to produce repetitive sequence domains of
      exact numbers of defined repeats. The complete synthetic HMW-glutenin construct
      was 1908 bp, and contained 32 identical copies of one of the HMW-glutenin
      repetitive domain motifs. The gene expressed the novel HMW-glutenin protein to
      relatively high levels in bacterial cultures and the protein exhibited the known
      anomalous behavior of HMW-glutenins in SDS-PAGE.

PMID- 8863729
TI  - Characterization of vitellogenin from rainbow trout (Oncorhynchus mykiss).
AB  - The nucleotide sequence of the vitellogenin cDNA from the rainbow trout
      Oncorhynchus mykiss was determined. Analysis of the deduced amino acid sequence
      (1659 residues) places the lipovitellin I, phosvitin and lipovitellin II domains
      between amino acids 16 to 1088, 1089 to 1145 and 1146 to 1659, respectively. The
      general structure is similar to other vertebrate vitellogenins except for the
      serine rich phosvitin domain which is the shortest identified so far in
      vertebrates (57 amino acids), being 2 to 4 times smaller than in other species.
      Sequence comparisons between vertebrate and invertebrate vitellogenins as well as
      with distantly related proteins allowed to identify two short amino acid motifs
      particularly well conserved, RGILN and TCGLCG in lipovitellin I and II domains,
      respectively, and strongly suggest that the lipovitellin II domain is involved in
      protein interactions via disulfide bridge formation.

PMID- 8863730
TI  - Structure of the human kappa-casein gene.
AB  - The human kappa-casein-encoding gene, Kca, was cloned and sequenced. The
      structural gene consists of five exons ranging from 33 to 496 nucleotides (nt)
      separated by introns ranging from 1146 to 2942 nt, and extends over 8821 nt. All
      intron/exon splice junctions conform to the GT/AG rule. The gene organization is
      similar to that of the bovine gene. The 5'-flanking region contains an A + T-rich
      sequence; TTTAATT, close to where the TATA motif is found in most other genes, a
      CAAT box, and an AP-1 consensus sequence. In addition, one Alu repetitive element
      was found in the second intron.

PMID- 8863731
TI  - A systematic survey of the intergenic region between the murine oxytocin- and
      vasopressin-encoding genes.
AB  - The genomic region between the oxytocin (OT) and vasopressin (VP) genes in the
      two strains of mice was independently sequenced by our two groups. In this
      report, we present our collated sequence data and analyses. The mouse intergenic
      region (MUIGR) was aligned to that of the rat, which has been reported to contain
      6.4-kb long interspersed nuclear element (LINE). The MUIGR sequences in the two
      mice strains did not contain any LINE sequences. This suggests that the
      approximately 3.5-kb sequence that is conserved between the rat and mouse
      intergenic regions is likely to be involved in the regulation of OT and VP
      expression. We also observed several conserved putative transcription factor
      recognition sequences. Analysis of the MUIGR revealed the lack of any significant
      ORFs, but the presence of several repetitive elements.

PMID- 8863732
TI  - Isolation of retinoic acid-repressed genes from P19 embryonal carcinoma cells.
AB  - Retinoic acid (RA) plays a critical role in normal development, growth and
      differentiation by modulating the expression of target genes. Using substractive
      hybridization cloning, we isolated two cDNAs, whose corresponding mRNAs are
      repressed upon RA treatment of P19 embryonal carcinoma (EC) cells. The cDNAs
      correspond to the serine hydroxymethyltransferase (shmt) gene and the early
      transposon, ETnMG1. RA appears to reduce the stability of ETnMG1 transcript. We
      also report the sequence of two different isoforms of mouse SHMT. Since SHMT
      activity is increased when cells are stimulated to proliferate and during the S
      phase of the cell cycle, we suggest that repression of shmt expression is an
      important step in RA-induced cell growth arrest and differentiation.

PMID- 8863733
TI  - Identification of the gene-richest bands in human chromosomes.
AB  - The human genome is a mosaic of isochores, long DNA segments which are
      compositionally homogeneous and which can be partitioned into five families, L1,
      L2, H1, H2 and H3, characterized by increasing GC levels and by increasing gene
      concentrations. Previous investigations showed that in situ hybridization with a
      DNA fraction derived from the GC-richest and gene-richest isochores of the H3
      family produced the highest concentration of signals on 25 R(everse) bands that
      include the 22 most thermal-denaturation-resistant T(elomeric) bands, a subset of
      R bands. Using an improved protocol for in situ hybridization and cloned H3
      isochore DNA, we have now shown (i) that the number of bands which are
      characterized by strong hybridization signals, and which are here called T or
      H3+, is 28; (ii) that 31 additional R bands, here called T'or H3* bands, also
      contain H3 isochores, although at a lower concentration than H3+ bands; and (iii)
      that the remaining R bands (about 140 out of 200, at a resolution of 400 bands),
      here called R" or H3- bands, do not contain any detectable H3 isochores. H3+ and
      H3* bands contain all the gene-richest isochores of the human genome. The
      existence of three distinct sets of R bands is further supported (i) by the
      different compositional features of genes located in them; (ii) by the very low
      gene density of chromosomes 13 and 18, in which all R bands are H3- bands; (iii)
      by the compositional map of a H3* band, Xq28; (iv) by the overwhelming presence
      of GC-rich and GC-poor long (> 50 kb) DNA sequences in H3+/H3* and in H3-/G
      bands, respectively; and (v) by the large degree of coincidence of H3+ and H3*
      bands with CpG island-positive bands. These observations have implications for
      our understanding of the causes of chromosome banding and provide a
      classification of chromosomal bands that is related to GC level (and to gene
      concentration).

PMID- 8863734
TI  - The gene distribution of the human genome.
AB  - Linear correlations exist between the GC levels of third codon positions (GC3) of
      individual human genes and the GC levels of long genomic sequences and DNA
      molecules (50-100 kb in size) embedding the genes. These linear relationships
      allow the positioning of the GC3 histogram of cDNA sequences from the databases
      relative to the CsCl profile of human DNA. In turn, this allows an estimate of
      the relative concentrations of genes in genomic regions of different GC content.
      An estimate obtained by using current sequence data and Gaussian decompositions
      of the GC3 histogram and of the CsCl profile indicates that the GC-richest (non
      ribosomal) component of the human genome is at least 17 times as gene-rich as the
      GC-poor regions. Moreover, our results suggest that the most recent physical maps
      of the human genome consisting of overlapping YACs cover less than 50% of the
      genes.

PMID- 8863735
TI  - Vector for IS element entrapment and functional characterization based on turning
      on expression of distal promoterless genes.
AB  - We constructed and characterized a novel trap vector for rapid isolation of
      insertion sequences. The strategy used for the isolation of IS elements is based
      on the ability of many IS elements to turn on the expression of otherwise silent
      genes distal to some sites of insertion. The simple transposition of an IS
      element can sometimes cause the constitutive expression of promoterless
      antibiotic resistance genes resulting in selectable phenotypes. The trap vector
      pAW1326 is based on a pBR322 replicon, it carries ampicillin and streptomycin
      resistance genes, and also silenced genes that confer chloramphenicol and
      kanamycin resistance once activated. The trap vector pAW1326 proved to be
      efficient and 85 percent of all isolated mutations were insertions. The majority
      of IS elements resident in the studied Escherichia coli strains tested became
      trapped, namely IS2, IS3, IS5, IS150, IS186 and Tn1000. We also encountered an
      insertion sequence, called IS10L/R-2, which is a hybrid of the two IS variants
      IS10L and IS10R. IS10L/R-2 is absent from most E. coli strains, but it is
      detectable in some strains such as JM109 which had been submitted to Tn10
      mutagenesis. The distribution of the insertion sequences within the trap region
      was not random. Rather, the integration of chromosomal mobile genetic elements
      into the offered target sequence occurred in element-specific clusters. This is
      explained both by the target specificity and by the specific requirements for the
      activation of gene transcription by the DNA rearrangement. The employed trap
      vector pAW1326 proved to be useful for the isolation of mobile genetic elements,
      for a demonstration of their transposition activity as well as for the further
      characterization of some of the functional parameters of transposition.

PMID- 8863736
TI  - Genomic structure of the maize TATA-box binding protein 1 (TBP-1): conserved
      exon/intron structure in eukaryotic TBP genes.
AB  - The gene system of the TATA-box binding protein (TBP) is well suited for the
      study of the evolutionary conservation of essential components of eukaryotic
      transcription initiation. In this context we have isolated and sequenced the
      maize TBP gene for a comparison with TBP genes from other organisms. In
      particular, a molecular phylogenetic analysis of the exon/intron structure of
      these genes including the archaeal TBP homolog (Thermococcus celer) was
      performed, revealing that the intron insertion probably occurred after the early
      appearance of the characteristic tandem repeat within the highly conserved C
      terminal domain of all known TBPs, but before separation of the eukaryotic
      progenitor into the different kingdoms.

PMID- 8863737
TI  - Characterization of new human c-myc mRNA species produced by alternative
      splicing.
AB  - Characterization of two human c-myc cDNAs corresponding to the mRNAs 2.5 and 3.1
      kb in length transcribed from P0 previously demonstrated the existence of
      alternative acceptor sites at the end of intron 1 and intron 2, respectively
      [Bentley, D.L. and Groudine, M. (1986) Mol. Cell. Biol. 6, 3481-3489]. We
      investigated the use of these alternative acceptor sites in each c-myc mRNA
      species. We characterized cDNAs corresponding to c-myc mRNAs transcribed in the
      SW613-S human carcinoma cell line. The use of the alternative acceptor site at
      the end of intron 1 was demonstrated in two out of 10 cDNAs corresponding to the
      3.1-kb mRNA transcribed from P0 and in three out of 10 cDNAs corresponding to the
      mRNAs transcribed from P1 or P2. The use of this acceptor site is therefore not
      restricted to the 2.5-kb mRNA transcribed from P0. The mRNAs resulting from the
      use of this acceptor site is therefore not restricted to the 2.5-kb mRNA
      transcribed from P0. The mRNAs resulting from the use of this acceptor site would
      encode for a variant form of the p67 polypeptide lacking one amino-acid residue.
      Conversely, the use of the alternative acceptor site at the end of intron 2 was
      not found in any of the cDNAs corresponding to the mRNAs transcribed from P0
      (0/10), from P1 or P2 (0/10) and from P3 (0/10). In the course of this study, we
      isolated a cDNA corresponding to another new c-myc mRNA species. This mRNA is
      produced by alternative splicing within intron 1 and encodes only for p64.

PMID- 8863738
TI  - A gyrB-like gene from the hyperthermophilic bacterion Thermotoga maritima.
AB  - We have cloned and sequenced two overlapping DNA fragments (3236 bp) containing a
      gene encoding the ATPase subunit of a type II DNA topoisomerase from the
      hyperthermophilic bacterion Thermotoga maritima (Tm Top2B). The deduced protein
      is composed of 636 aa with a calculated molecular mass of 72415 Da. It shares
      significant similarities with the ATPase subunits of mesophilic bacterial DNA
      topoisomerases II, either DNA gyrase (GyrB) or DNA topoisomerase IV (ParE).
      Although the highest similarity scores are obtained with GyrB proteins (55%
      identity with Bacillus subtilis DNA gyrase), a detailed phylogenetic analysis of
      all known DNA topoisomerases II does not allow us to determine if Tm Top2B
      corresponds to a DNA gyrase or a DNA topoisomerase IV. This hyperthermophilic
      Top2B protein exhibits a larger amount of charged amino acids than its mesophilic
      homologues, a feature which could be important for its thermostability. No gyrA
      like gene has been found near top2B. A gene coding for a transaminase B-like
      protein was found in the upstream region of top2B.

PMID- 8863739
TI  - Molecular cloning of two novel rab genes from human melanocytes.
AB  - We isolated the genes of two small GTP-binding proteins of the rab family from a
      human melanocyte cDNA library and from melanoma cells. One gene, rab30 codes for
      a novel rab protein of 203 amino acids with minimal homology to previously
      documented GTPases. The other, rab22b, appears to be an isoform of the human
      homologue of canine rab22. Both rab mRNAs displayed a nearly ubiquitous pattern
      of expression in the various tissues examined. Rab22b and rab30 were mapped to
      chromosomes 18 and 11, respectively.

PMID- 8863740
TI  - Molecular cloning, expression and chromosomal localization of a human gene
      encoding a 33 kDa putative metallopeptidase (PRSM1).
AB  - The zincins are a superfamily of structurally-related Zn(2+)-binding
      metallopeptidases which play a major role in a wide range of biological processes
      including pattern formation, growth factor activation and extracellular matrix
      synthesis and degradation. In this paper we report the identification and
      complete primary structure of a novel 33 kDa protein which contains the zinc
      binding HEXXH motif found in the zincin superfamily. We have named this novel
      protein PRSM1 (PRoteaSe, Metallo, number 1). The gene was identified by the
      immunoscreening of a human placental cDNA library using polyclonal antibodies
      raised to the 70 kDa human matrix metalloendopeptidase, type III procollagen N
      proteinase [Halila, R. and Peltonen, L. (1986) Purification of human procollagen
      type III N-proteinase from placenta and preparation of antiserum. Biochem. J.
      239, 47-52]. The protein is found in placenta and cultured osteosarcoma cells.
      PRSM1 could share sequence homology with the type III procollagen N-proteinase.
      The prsm1 gene is represented once in the human genome and is localized on
      chromosome 16 (q24.3).

PMID- 8863741
TI  - A group II intron in a conjugative transposon from the gram-positive bacterium,
      Clostridium difficile.
AB  - We have been studying the conjugative transposon Tn5397, originally isolated from
      the Gram-positive pathogen Clostridium difficile. Physical analysis of this
      transposon demonstrated that it contained a group II intron. This is the first
      report of an intron in a conjugative transposon and the first report of a group
      II intron in Gram-positive bacteria. The intron interrupted a gene in Tn5397 that
      is almost identical to orf14 from Tn916. DNA hybridisation analysis showed that
      elements related to Tn5397, containing the group II intron, were present in five
      other C. difficile strains from different geographical locations suggesting that
      the element is likely to be widely distributed.

PMID- 8863742
TI  - Expression profiles of active genes in human and mouse livers.
AB  - An expression profile of active genes in the human liver was obtained by
      collecting sequences with a 3'-directed cDNA library that faithfully represents
      composition of the mRNA population. The results show the relative activity of ca.
      600 genes in maintaining the hepatocytes and sustaining their liver-specific
      phenotypes. The most active group of genes are those for the production of plasma
      proteins, followed by the genes for the synthesis of lipoproteins, protease
      inhibitors, coagulation factors, and complements. This balance of gene activity
      was maintained for four independently obtained expression profiles from human
      livers, including those of adult and fetus. The expression profiling was extended
      to the liver of adult mouse, used as a model for the molecular etiology of
      hepatocytes and for examining the effects of drugs. Subtle biological differences
      between the human and mouse livers are reflected in the global expression
      profiles of active genes, especially with regard to the synthesis of plasma
      proteins, lipoproteins and complements. This comparative analysis using
      expression profiling should find a wide application in comparative biology.

PMID- 8863743
TI  - Molecular cloning of fish alcohol dehydrogenase cDNA.
AB  - A cDNA encoding a putative alcohol dehydrogenase class III (ADH) was cloned from
      a cDNA library constructed from 7-day larvae RNA of the marine teleost Sparus
      aurata. The full length cDNA is 1350 nucleotides (nt) long and contains an ORF of
      1128 nt [encoding 376 amino acid (aa) residues]. Identity of 82% was found with
      human class III ADH (305 of 372 aa compared), and only 62% identity with a fish
      (cod) ADH (234 of 375 aa compared). Northern hybridization analysis with the cDNA
      revealed a transcript of about 1.4-1.5 kb, which is expressed in all tissues from
      adult fish studied: skeletal muscle, heart muscle, kidney, gill filaments and
      liver, with the highest levels found in the kidney. The expression of ADH mRNA
      was determined also during early development of Sparus aurata by Northern blot
      analysis. ADH transcripts were detected in eggs and in embryos 4, 8 and 12 h
      after fertilization, as well as on all days post-hatching studied. The levels of
      expression decreased during early embryonal development, but increased 4-fold
      from day 1 to day 21 after hatching. The size of the transcript was identical to
      that of hepatic ADH. Our results suggest that maternal ADH mRNA is present in the
      eggs and embryos, which decreases as divisions and development occur, while after
      hatching ADH mRNA is expressed by the larval tissues.

PMID- 8863744
TI  - Distribution and variability of trinucleotide repeats in the genome of the yeast
      Saccharomyces cerevisiae.
AB  - We have examined the distribution of trinucleotide repeats in the yeast genome.
      Perfect and imperfect repeats, ranging from four to 130 triplets were recognized
      and the repartition of different triplet combinations was found to differ between
      Open Reading Frames and Intergenic Regions. Examination of different laboratory
      strains, revealed polymorphic size variations for all perfect repeats studied,
      compared to an absence of variation for the imperfect ones. Size variations were
      found discrete in the range of 6-18 triplets, each strain showing one allelic
      form for a given repeat array. The distribution and stability of trinucleotide
      repeats in the yeast genome resembles that of humans and may provide an
      experimental approach to study the mechanisms of their expansion.

PMID- 8863745
TI  - Insertion of a short Alu sequence into the hMSH2 gene following a double cross
      over next to sequences with chi homology.
AB  - Alu repeat sequences and other multiple copy repetitive elements are present
      throughout the human genome and are active in promoting recombination. It is
      believed that reverse transcription of transcribed Alu repeats followed by
      chromosomal integration has been responsible for the wide dispersion and high
      copy number of these sequences. During studies on the hMSH2 gene we have used RT
      PCR to amplify from peripheral blood lymphocytes a cDNA species in which 553 base
      pairs of hMSH2 cDNA have been deleted to be replaced by a short 36 base pair Alu
      sequence as a result of a genomic insertion/deletion event. The 36 base pair Alu
      insert is homologous to a 26 base pair Alu sequence previously implicated in the
      promotion of recombination and contains the GCTGG motif which is part of the
      prokaryotic chi sequence. A second chi-like sequence is also located within the
      deleted hMSH2 region. Both chi-like sequences are located within 4 bp of the two
      4-bp regions of cross over containing the insertion/deletion breakpoints. This
      suggest that a double recombination event has occurred, providing direct evidence
      for the recombinogenic activity of this Alu element. Furthermore, it suggests
      that chi-like sequences may define recombination hotspots as in prokaryotes.

PMID- 8863746
TI  - Sequence analysis of the beta B2-crystallin cDNA of hamster containing a domain
      conserved among vertebrates.
AB  - The cDNA sequence of the beta B2-cry was determined from hamster (Mesocricetus
      auratus) and compared to the corresponding genes of bovine, frog, chicken, human,
      mouse and rat. Multispecies comparison demonstrated high homology between the
      hamster, rat and mouse gene, but larger distances to man, bovine, chicken and
      frog. There is striking identity within a strech of 36 deduced amino acids (aa)
      between the Greek key motif 3 and part of motif 4. This 36-aa domain contains a
      putative phosphorylation site for protein kinase C and is highly conserved among
      all known basic beta B-Cry; however, it can neither be detected in the acidic
      beta A-nor in the gamma-Cry.

PMID- 8863747
TI  - Structure and organization of the mouse elk1 gene.
AB  - In the ets gene family of transcription factors, elk1 belongs to the subfamily of
      Ternary Complex Factors (TCFs) which bind to the Serum Response Element (SRE) in
      conjunction with a dimer of Serum Response Factors (SRFs). In this communication
      we report the isolation of cDNAs from the mouse elk1 gene, containing the full
      coding sequence homologous (87% identical) to the human gene, and the structure
      and organization of 22 kb of the mouse elk1 locus. The coding sequence is spread
      through 5 exons (numbered 1 to 5): exons 1 to 4 range from 102 bp to 447 bp and
      exon 5 is at least 620 bp. Exon 0 was not found in the 8.5 kb sequence upstream
      of exon 1. The intron between exons 1 and 2 is 4 kb long and the 3 other introns
      are less than 500 bp long. This information will be useful to engineer targeted
      mutations of this gene in mice and to determine the genomic structure of the
      other TCF genes.

PMID- 8863749
TI  - Managed care: seeking the right balance.

PMID- 8863750
TI  - Hemlock Society medical director defends 'physician aid-in dying'.

PMID- 8863751
TI  - Palliative care: how do you manage "other' distressing symptoms?

PMID- 8863753
TI  - Dressing wound care with less skin irritation.

PMID- 8863752
TI  - Geriatrics photo quiz. Addison's anemia.

PMID- 8863754
TI  - Brown patches, skin tags on axilla. Are this patient's velvety plaques related to
      his obesity and diabetes?

PMID- 8863755
TI  - Depression: making the diagnosis and using SSRIs in the older patient.
AB  - Depression often goes unrecognized and untreated in older adults, in part because
      of its atypical presentation and the comorbid medical conditions in this
      population. Depression may coexist with dementia and is more often seen in
      patients with certain medical illnesses. Drug therapy is effective in treating
      depression in 65 to 75% of older patients. Selective serotonin reuptake
      inhibitors (SSRIs) are often used in this population because of their proven
      efficacy, safety, and tolerability. The most common side effects of SSRIs are GI
      disturbances and headaches, which may be minimized by slow dose escalation.
      Compared with younger adults, the elderly generally require smaller doses but
      show a similar time course of response to anti-depressant therapy.

PMID- 8863756
TI  - Managed care: what to expect as Medicare-HMO enrollment grows. 1.
AB  - Managed care is restructuring the American health care system and is beginning to
      make inroads into the Medicare-eligible population. Advantages of managed care
      for older patients include an emphasis on prevention, more flexibility in care
      delivery, and fewer restrictions and wider coverage (eg, prescriptions) than
      Medicare fee-for-service, and opportunities to develop measures for quality of
      care. Disadvantages include limitations on access and choice and a potential for
      professional conflict of interest. Early managed care enrollment favors the
      healthy "young-old;" questions remain about whether HMOs can provide quality care
      to the frail elderly with complicated and expensive health care needs.

PMID- 8863757
TI  - Treating alcoholism: an age-specific intervention that works for older patients.
AB  - Alcoholism occurs in 10 to 15% of the population over age 65 and may be difficult
      to diagnose. The diagnosis is based on a history aimed at detecting behavioral
      problems associated with drinking, administering an in-office screening
      instrument, and conducting tests of liver function and/or mean corpuscular
      volume. The most effective treatment approach in this population focuses on the
      stresses of aging and co-existing depression, rather than on alcohol use itself.
      This approach has been found equally effective in long-standing alcoholics and
      those who develop a drinking problem in late life. Generally, older alcoholics
      are very responsive to treatment.

PMID- 8863758
TI  - A matter of degree.

PMID- 8863759
TI  - Cardiorespiratory responses of patients with rheumatoid arthritis during bicycle
      riding and running in water.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare exercise during
      dry-land bicycle ergometry and running in water with a flotation device in
      individuals with rheumatoid arthritis. SUBJECTS: Eight individuals with adult
      onset rheumatoid arthritis, between the ages of 30 and 40 years (X = 35.88, SD =
      2.85), participated. METHODS: Each subject did a graded maximal exercise test on
      a stationary bicycle and in the water wearing a flotation device, while oxygen
      uptake (VO2), heart rate (HR), pain, rating of perceived exertion (RPE), minute
      ventilation (VE), respiration rate, tidal volume (VT), and respiratory exchange
      ratio (R) were monitored. RESULTS: Higher maximum RPE and R were seen during
      water running, whereas higher VE and VT were seen during bicycle riding. Heart
      rate, R, and plateauing VO2 data indicated that a true physiological peak VO2 was
      reached during the bicycle test. Peak VO2 and HR were similar for either water or
      bicycle exercise. These findings show that with both forms of exercise, subjects
      were able to reach training levels as set by the American College of Sports
      Medicine. CONCLUSION AND DISCUSSION: The water exercise, therefore, provides a
      means of exercising for individuals with rheumatoid arthritis. It allows them to
      reach the needed training levels in a comfortable aquatic environment.

PMID- 8863760
TI  - Lumbar lordosis and pelvic inclination of asymptomatic adults.
AB  - BACKGROUND AND PURPOSE: We examined the association between pelvic inclination
      and lumbar lordosis during relaxed standing and eight variables thought to
      contribute to lordosis. SUBJECTS: Ninety subjects (45 men, 45 women) without back
      pain or a history of surgery were examined. The mean age was 54.8 years (SD =
      8.5) for male subjects and 58.9 years (SD = 8.8) for female subjects. METHODS:
      Multiple linear regression modeling was used to assess the association of pelvic
      inclination and size of lumbar lordosis in a standing position with age, gender,
      body mass index, physical activity level, back and one-joint hip flexor muscle
      length, and performance and length of abdominal muscles. RESULTS: Abdominal
      muscle performance was associated with angle of pelvic inclination for women (R2
      = .23), but not for men. Standing lumbar lordosis was associated with abdominal
      muscle length in women (R2 = .40), but it was multivariately associated with
      length of abdominal and one-joint hip flexor muscles and physical activity level
      in men (R2 = .38). No correlation was found between angle of pelvic inclination
      and depth of lumbar lordosis in a standing position. CONCLUSION AND DISCUSSION:
      Neither univariate nor multivariate regression models account for variability in
      the angle of pelvic inclination or size of lumbar lordosis in adults during
      upright stance; no correlation was found in standing between these two variables.
      The use of abdominal muscle strengthening exercises or stretching exercises of
      the back and one-joint hip flexor muscles to correct faulty standing posture
      should be questioned.

PMID- 8863761
TI  - The effect of brochure use versus therapist teaching on patients performing
      therapeutic exercise and on changes in impairment status.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate whether the
      mode of teaching exercises (use of brochures versus therapist teaching) affects
      whether patients correctly perform the exercises and whether it affects changes
      in impairment. SUBJECTS: Eighty-seven patients (33 women, 54 men) with neck pain
      and low back pain were examined. The average age was 48 years (SD = 12.7, range =
      21-67). METHODS: Two groups of patients were analyzed. The supervised (physical
      therapist-instructed) group (n = 47) exercised under the supervision of a
      physical therapist, whereas the brochure group (n = 40) received their
      instructions only from one of three brochures. A rating scale was used to assess
      the correctness of exercise performance. Muscle status was registered using a
      standardized procedure for determination of muscle force and length. Pain
      severity was determined by means of a visual analogue scale. RESULTS: On the
      rating scale evaluating the correctness of exercise performance at follow-up, the
      patients in the supervised group performed better than the patients in the
      brochure group. In addition, there was a strong correlation between the quality
      of exercise performance and decrease in pain. CONCLUSION AND DISCUSSION:
      Exercises learned only from a brochure without being monitored by a physical
      therapist were done properly by only about half of the patients and appeared to
      result in fewer improvements in impairments.

PMID- 8863762
TI  - Amount of patient education in physical therapy practice and perceived effects.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the amount
      and perceived effects of informal patient education in physical therapy practice.
      SUBJECTS: Thirty-seven physical therapists from nine outpatient physical therapy
      settings participated. METHODS: Each therapist audiotaped the entire course of
      treatment for one patient. The frequency of patient education statements in five
      categories (information about illness, home exercises, advice and information,
      health education, and stress counseling) was counted. Therapists, patients, and
      supervisors completed questionnaires about the amount and perceived effects of
      these teaching behaviors. RESULTS AND CONCLUSIONS: The greatest numbers of
      educational statements were in the categories of information about illness (X =
      4.72 statements per session), home exercises (X = 3.98 statements per session),
      and advice and information (X = 2.54 statements per session). The therapists'
      teaching behaviors rarely corresponded to their perceptions of their own teaching
      or to their patients' or supervisors' perceptions.

PMID- 8863763
TI  - The identification of ethical issues in physical therapy practice.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to identify the current
      ethical issues facing physical therapists and (2) ethical issues that may be
      faced in the future by physical therapists. SUBJECTS AND METHODS: The Delphi
      technique was used as the research design for this study. The panel of experts
      for the study were selected from Papers submitted by past and present members of
      the Judicial Committee of the American Physical Therapy Association. A series of
      three questionnaires were sent to the members of the panel. Following the Delphi
      technique, the first questionnaire contained broad questions designed to elicit a
      wide range of responses. The second and third questionnaires were then developed
      from the information received in the preceding questionnaire. RESULTS: The
      results of the first question of the study identified 10 current ethical issues
      as consensus choices by the panel and 3 issues as near-consensus. The panel
      responses to the second question identified 4 future ethical issues. A combined
      list of current and future contained 16 issues in physical therapy. CONCLUSION
      AND DISCUSSION: The 16 issues addressed ethical considerations in different areas
      of physical therapy practice: 6 issues involving patient rights and welfare, 5
      professional issues, and 5 issues relating to business and economic factors.
      Thirteen of these issues have not been discussed in previous physical therapy
      literature and would be suggested topics for future study.

PMID- 8863764
TI  - Health status measures: strategies and analytic methods for assessing change
      scores.
AB  - Over the last 15 years, numerous self-report health status measures have appeared
      in the literature. An important parallel development has been the development of
      numerous strategies for assessing change in health status over time. The purpose
      of this article is to summarize and critique the more common design and analytic
      strategies for assessing the meaningfulness of change over time. Five commonly
      reported designs are presented, critiqued, and depicted using examples from the
      literature. Methods for analyzing results are reviewed and illustrated using two
      data sets. Insights into comparing competing health status measures are provided.
      In summary, the article suggests that some designs and analytic strategies are
      more adept than others at assessing change and that these methods should be
      considered when planning sensitivity-to-change studies.

PMID- 8863765
TI  - Berg balance test.

PMID- 8863766
TI  - Berg balance test.

PMID- 8863767
TI  - Bylaws of the American Physical Therapy Association.

PMID- 8863768
TI  - Standing rules of the American Physical Therapy Association.

PMID- 8863769
TI  - Hypotensive reactions: are they a new phenomenon? Are they related solely to
      transfusion of platelets? Does filtration of components play a role?

PMID- 8863770
TI  - The Viral Activation Transfusion Study (VATS): rationale, objectives, and design
      overview.

PMID- 8863771
TI  - Human immunodeficiency virus type 1 activation after blood transfusion.
AB  - BACKGROUND: Anemia and transfusion are predictors of disease progression in AIDS
      patients. This study was designed to examine the effects of blood transfusion on
      human immunodeficiency virus type 1 (HIV-1) expression. STUDY DESIGN AND METHODS:
      Assays of plasma viral load were performed before and after transfusion in nine
      HIV-1-infected patients who required blood transfusion for refractory anemia.
      RESULTS: There was a modest rise in plasma HIV-1 p24 antigen and plasma HIV-1 RNA
      beginning 1 to 2 weeks after the blood transfusion. The mean change in plasma p24
      antigen for all patients was 9.3 +/- 5.1 (mean +/- SE) pg per mL at Week 2 after
      transfusion and 18 +/- 11.1 pg per mL at Week 4. Plasma HIV-1 RNA levels were
      unchanged immediately after transfusion and exceeded pretransfusion levels with a
      mean rise of 84 +/- 40 percent (SE) at Week 1, 70 +/- 27 percent at Week 2, and
      67 +/- 38 percent at Week 4 (p = 0.006, exact permutation test). There was no
      increase in spontaneous or interleukin 2-induced lymphocyte proliferation or p24
      antigen production by patients' lymphocytes that were examined immediately after
      blood transfusion. CONCLUSION: The transfusion of blood to persons with advanced
      HIV-1 infection modestly increases plasma levels of HIV-1. The activation of HIV
      1 expression by transfusion may help to explain the accelerated course of HIV-1
      disease in recipients of blood transfusion.

PMID- 8863772
TI  - Virus inactivation by pepsin treatment at pH 4 of IgG solutions: factors
      affecting the rate of virus inactivation.
AB  - BACKGROUND: IgG preparations have rarely transmitted infectious diseases;
      however, because such transmission has occurred a few times, manufacturers are
      required to present experimental proof that their specific production process
      removes and/or inactivates viruses that may be present in the starting material.
      STUDY DESIGN AND METHODS: The kinetics of virus inactivation mediated by pepsin
      treatment at pH 4 during the production of intravenous immunoglobulin was
      assessed with spiking experiments using human immunodeficiency virus, bovine
      viral diarrhea virus, Semliki Forest virus, and pseudorabies virus. The influence
      of various factors on the rate of virus inactivation also was studied by
      modifying the composition of the IgG solutions with respect to IgG, sucrose, and
      NaCl content. RESULTS: Virus inactivation at 37 degrees C was extremely rapid and
      resulted in a complete loss of infectivity within 5 minutes to 1 hour.
      Inactivation was much slower at lower temperatures. Furthermore, inactivation was
      dependent on the solute composition. Increasing the sucrose content from 0 to 15
      percent reduced the rate of inactivation of pseudorabies virus but did not affect
      the rate of inactivation of Semliki Forest virus. In contrast, increasing the
      NaCl content from 0 to 150 mM resulted in a reduction in the rate of inactivation
      of Semliki Forest virus, whereas the rate of inactivation of pseudorabies virus
      remained unaffected. Moreover, increasing the IgG concentration from 0 to 10
      percent resulted in an increased rate of inactivation of pseudorabies virus but a
      decreased rate of inactivation of Semliki Forest virus. CONCLUSION: Inactivation
      of viruses by pepsin treatment at pH 4 essentially is temperature-dependent, and
      the reaction rate is selectively influenced by the solute composition of the IgG
      solution. This has to be taken into account when safety data for different
      products are compared.

PMID- 8863774
TI  - Large-volume leukapheresis in pediatric patients: processing more blood
      diminishes the apparent magnitude of intra-apheresis recruitment.
AB  - BACKGROUND: Recruitment of progenitors during a large-volume collection, as
      defined by increasing relative and absolute numbers of progenitors (colony
      forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported
      previously. STUDY DESIGN AND METHODS: To ascertain whether intra-apheresis
      recruitment occurs in pediatric patients who have undergone mobilization with
      chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's
      portion of a 4-hour leukapheresis was collected into separate bags, and assessed
      by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients
      (median age, 7; range, 2-19) were studied in connection with 2 to 4 collections
      each, for a total of 21 collections (with hourly samples). The collections lasted
      for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily
      processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated
      by the patient's weight in kg x 70 mL/kg.) Smaller (younger) patients had inlet
      rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of
      1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of
      the collection and divided by the first hour's value were compared by
      nonparametric repeated-measures ANOVA. RESULTS: Second-, third- and fourth-hour
      CD34+ progenitor cell counts were arithmetically higher than first-hour counts,
      but the trend did not reach significance (p = 0.1561). Second-hour counts were
      higher than first-hour counts in the overall analysis (mean +/- standard error
      [SE], 1.00 and 1.39 +/- 0.1, respectively; p = 0.0525) and in children older than
      5 years (1.00 vs. 1.70 +/- 0.30, respectively; p = 0.0259), but not in children
      younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours
      of collection (p = 0.1717) or between the first and second hour (p = 0.9587).
      CONCLUSION: In larger (older) patients, from whom fewer blood volumes were
      collected, there is a trend toward intra-apheresis recruitment, although less
      than reported previously. In the smaller (younger) patients, from whom more blood
      volumes were collected, no trend was observed. Lack of (or submaximal) prior
      mobilization in previously reported studies may have facilitated intracollection
      recruitment. Alternatively, the larger number of blood volumes collected from the
      smaller (younger) patients may have masked intra-apheresis recruitment. The study
      documents the feasibility of large-volume, 4-hour leukapheresis in pediatric
      patients.

PMID- 8863773
TI  - AS-1 red cells for neonatal transfusions: a randomized trial assessing donor
      exposure and safety.
AB  - BACKGROUND: Despite recent optimism about the use of erythropoietin therapy to
      treat the anemia of prematurity, very-low-birth-weight infants who are severely
      ill receive multiple red cell (RBC) transfusions. Many physicians transfuse
      relatively fresh RBCs to newborn infants, exposing them to multiple donors and
      possibly increasing their risk of acquiring transfusion-transmitted infections.
      STUDY DESIGN AND METHODS: A randomized, single-blind clinical trial was conducted
      to determine, as the primary endpoint, whether RBCs collected from one dedicated
      donor and stored for < or = 42 days in AS-1 storage media could safely supply all
      small-volume RBC transfusions (15 mL/kg/dose) needed by very-low-birth-weight
      infants (0.6-1.3 kg) during the first 84 days of life. Secondary endpoints were
      the assessment of the possible adverse clinical and biochemical effects of
      transfusing AS-1 RBCs stored for < or = 42 days. Control infants received
      identical nursery care, except they received fresh RBCs stored < or = 7 days in
      CPDA-1. RESULTS: Infants transfused with AS-1 RBCs were exposed to a mean of 1.6
      donors,-compared with an exposure to 3.7 donors for infants given CPDA-1 RBCs (p
      < 0.05). Neither clinical transfusion reactions nor the results of multiple
      laboratory tests were significantly different in infants who received slow
      transfusions (15 mL/kg) of AS-1 RBCs stored for < or = 42 days and in infants who
      received the same volume of CPDA-1 RBCs stored < or = 7 days. CONCLUSION: AS-1
      RBCs, usually from only one dedicated donor, can safely supply all RBCs needed by
      most very-low-birth-weight infants-a practice that decreases donor exposure and
      likely increases transfusion safety.

PMID- 8863775
TI  - Febrile reactions to platelet transfusion: the effect of increased interleukin 6
      levels in concentrates prepared by the platelet-rich plasma method.
AB  - BACKGROUND: A relation between febrile reactions to platelet transfusion and high
      cytokine levels in platelet concentrates (PCs) was found previously. The levels
      of cytokines such as interleukin (IL)-6 are related to the while cell content of
      the PC during storage. Therefore, early removal of white cells should prevent
      reactions. STUDY DESIGN AND METHODS: This prospective study was set up to compare
      methods for the preparation of random PCs, the platelet-rich plasma method (PRP
      PCs), which results in a high white cell content, and the buffy coat method (BC
      PCs), which results in a low white cell content, with regard to the frequency and
      severity of reactions to platelet transfusion and the IL-6 level of the PC. IL-6
      was chosen because it is the major mediator of the acute-phase response. White
      cells were reduced in all PCs before transfusion. RESULTS: Platelet transfusions
      (n = 584) in 64 patients were studied. An overall reaction frequency of 7.2
      percent was observed. Transfusion reactions were seen predominantly in patients
      who received PRP-PCs (PRP-PCs: 9.3% vs. BC-PCs: 2.7%, p = 0.007). Allergic
      reactions were limited to transfusions of PRP-PCs. The following PRP-PC
      characteristics were significantly correlated with febrile transfusion reactions:
      IL-6 level (p < 0.0001), initial white cell count (p = 0.001), and storage time
      (p = 0.02). In this group, reactions were less frequent in patients receiving
      pretransfusion medication (p < 0.001). In the PRP-PC group, IL-6 content (p =
      0.01) and initial white cell count (p = 0.04) were also significantly correlated
      with allergic reactions, which indicated that these or associated factors might
      have an effect on the outcome of this type of reaction. CONCLUSION: Febrile
      reactions are highly correlated with IL-6 levels in PCs. The low white cell
      content of BC-PCs is associated with undetectable IL-6 levels and a reduced
      frequency of febrile as well as allergic reactions in recipients. The BC method
      is the preferable one for the production of random-donor PCs.

PMID- 8863776
TI  - Frequency and functional relevance of genetic threonine145/methionine145
      dimorphism in platelet glycoprotein Ib alpha in an Italian population.
AB  - BACKGROUND: Threonine145/methionine145 dimorphism in platelet glycoprotein (GP)
      Ib alpha defines the human platelet antigen (HPA)-2 system that has been
      implicated in refractoriness to HLA-matched platelet transfusion and in neonatal
      immune thrombocytopenic purpura. STUDY DESIGN AND METHODS: The occurrence of this
      amino acid dimorphism was investigated in 379 Italian blood donors by studying
      their genomic DNA. Two oligonucleotide primers, Ib alpha-3 (5'
      GGACGTCTCCTTCAACCGGC-3') and Ib alpha-4 (5'-GCTTTGGTGGGGAACTTGAC-3'), were used
      in a polymerase chain reaction to generate a 591-base pair fragment that was
      digested with the restriction enzyme Acy I. To investigate whether this
      dimorphism is involved in the binding of von Willebrand factor (vWF) to GPlb, the
      binding of vWF to the GPlb/IX complex was measured in two Met145/Met145 and two
      Thr145/Thr145 subjects. RESULTS: The genotypic frequencies are 78.9% for Thr/Thr,
      19.8% for Thr/Met), and 1.3% for Met/Met; the allelic frequencies are 88.8% for
      Thr145 and 11.2% for Met145. Estimates for binding of subunit molecules per
      platelet at saturation and inhibition constant in mol per L, respectively,
      follow. In the presence of ristocetin (0.5 mg/mL), they are 11,460 +/- 2,040 and
      1.26 +/- 0.44 x 10(-8) for normals and 11,230 +/- 2,330 and 1.29 +/- 0.48 x 10(
      8) for patients. In the presence of botrocetin (2.5 micrograms/mL), they are
      64,260 +/- 7,760 and 2.99 +/- 0.96 x 10(-8) for normals and 65,770 +/- 11,570 and
      2.47 +/- 0.22 x 10(-8) for patients. Platelet aggregation responses obtained
      using platelet-rich plasma from donors with Met145/Met145 or Thr145/Thr145
      genotype were within normal limits. CONCLUSION: Genotypic and phenotypic
      frequencies in the HPA-2 system in this population are consistent with those
      reported among the white population. Furthermore, the HPA-2 system is not
      involved in the binding of vWF to GPlb.

PMID- 8863777
TI  - Determination of neutrophil antigen gene frequencies in five ethnic groups by
      polymerase chain reaction with sequence-specific primers.
AB  - BACKGROUND: The granulocyte antigens NA1 and NA2 are the two recognized allelic
      forms of Fc gamma receptor IIIB. These antigens are clinically relevant, because
      they are the most frequent targets of neutrophil antibodies in alloimmune
      neonatal neutropenia, transfusion-related acute lung injury, and chronic benign
      autoimmune neutropenia of infancy. STUDY DESIGN AND METHODS: A genotyping assay
      for NA1 and NA2 using polymerase chain reaction with sequence-specific forward
      and reverse oligonucleotide primers has been developed and validated. Genomic DNA
      was isolated from the peripheral blood of 478 unrelated individuals of five
      ethnic groups and used as template for NA genotyping. RESULTS: A validation study
      of 22 serologically typed samples (2 NA1/NA1, 10 NA1/NA2, and 10 NA2/NA2) was
      performed. A concordance rate of 100 percent (22/22 samples) was observed between
      the genotyping assay and serologic typing. In the genotyping study conducted, the
      NA1 and NA2 gene frequencies observed were 0.31 and 0.69 for African Americans,
      0.30 and 0.70 for Asian Indians, 0.37 and 0.63 for whites, 0.53 and 0.47 for
      Hispanics, and 0.55 and 0.45 for Native Americans, respectively. CONCLUSION:
      Polymerase chain reaction with sequence-specific primers provides a simple and
      rapid alternative to neutrophil antigen typing by serologic tests. The NA1 and
      NA2 gene frequencies observed in Asian Indians and African American populations
      are similar to those observed in white populations, while those observed in
      Native American and Hispanic populations are more similar to those previously
      reported for Asian populations.

PMID- 8863778
TI  - Hypotensive reactions to white cell-reduced plasma in a patient undergoing
      angiotensin-converting enzyme inhibitor therapy.
AB  - BACKGROUND: Hypotensive reactions to platelet transfusions performed with white
      cell (WBC)-reduction filters with negatively charged surfaces have been reported
      recently in patients taking angiotensin-converting enzyme (ACE) inhibitors.
      Experimental studies have shown that the filter material can activate bradykinin,
      which may cause symptoms in patients with reduced bradykinin catabolism.
      Symptomatic adverse reactions after the administration of fresh-frozen plasma
      (FFP) through a WBC-reduction filter have not been reported in a patient on ACE
      Inhibitor medication. CASE REPORT: A 58-year-old man with congenital coagulation
      factor V deficiency and hypertension treated with an ACE inhibitor was admitted
      for rehabilitation after orthopedic surgery. On 3 consecutive days, he received
      FFP through a WBC-reduction filter; within minutes of the beginning of each
      infusion, he experienced a drop in blood pressure, facial erythema, abdominal
      pain, and anxiety. When the infusions were stopped, symptoms quickly abated
      without treatment. Multiple prior transfusions of unfiltered FFP and FFP filtered
      through a WBC-reduction filter made by a different manufacturer, as well as
      subsequent transfusions of unfiltered FFP, had not produced such reactions.
      CONCLUSION: Facial flushing, hypotension, and abdominal pain after FFP
      administration in a patient on ACE inhibitor medication appeared to be associated
      with a specific type of WBC-reduction filter. This association and other reported
      studies suggest that special caution is warranted when patients who are treated
      with ACE inhibitors receive blood components administered through WBC-reduction
      filters capable of generating bradykinin.

PMID- 8863779
TI  - Hypotensive reactions: a previously uncharacterized complication of platelet
      transfusion?
AB  - BACKGROUND: In 1993, the American Association of Blood Banks (AABB) received
      reports of severe hypotensive reactions associated with platelet transfusions.
      The question arose as to whether these reports were indicative of a previously
      uncharacterized platelet transfusion reaction. STUDY DESIGN AND METHODS: To
      further characterize these reactions, the AABB Transfusion Practices Committee
      developed a series of three questionnaires. The initial questionnaire was sent to
      all AABB institutional members; the two subsequent questionnaires were sent to
      those institutions reporting severe and/or unusual platelet transfusion
      reactions. This report focuses on the 24 responses to the third and most detailed
      questionnaire, which specifically addressed reactions that were characterized by
      hypotension and/or unexplained respiratory failure. RESULTS: Of the 24 detailed
      responses received, 4 were not considered to represent unusual reactions to
      platelet transfusion, 3 described reactions consistent with a (presumably
      unrecognized) diagnosis of transfusion-related acute lung injury, and 17
      described reactions that were primarily characterized by hypotension. The
      majority of the hypotensive reactions occurred within 1 hour of the beginning of
      the transfusion (88%), were associated with respiratory distress (82%), and
      resolved rapidly after cessation of the transfusion (82%). Eighty-eight percent
      of implicated components had been white cell reduced by filtration. CONCLUSION:
      The hypotensive platelet transfusion reactions that were described appear to
      represent a previously uncharacterized complication of platelet transfusion.
      However, the nature of the questionnaires used in this investigation does not
      allow the drawing of firm conclusions as to the frequency or the cause of these
      reactions.

PMID- 8863780
TI  - Purging: the separation of normal from malignant cells for autologous
      transplantation.

PMID- 8863781
TI  - HIV and the blood supply: an analysis of crisis decision making. Executive
      summary. The Institute of Medicine, National Academy of Sciences Committee to
      Study HIV Transmission Through Blood and Blood Products.

PMID- 8863782
TI  - Blood safety decisions, 1982 to 1986: perceptions and misconceptions.
AB  - Although blood bankers and those who treat persons with hemophilia are supportive
      of most of the recommendations of the Report, the manner in which the analysis
      was conducted and some of the general conclusions that were reached appear
      flawed. The flaws may reflect the deficiencies in the process by which the
      Committee gathered data more than any bias on the part of its members themselves.
      The Report may accurately reflect the testimony heard, but it is biased by the
      committee's acceptance as fact the opinions of critics who claim the AIDS
      epidemic was mismanaged by the blood-collecting agencies, professional
      organizations, hemophilia organizations, and the federal government.
      Countervailing views on the various issues are ignored or incompletely discussed.
      Much testimony was taken from the victims of the transfusion-associated AIDS
      epidemic. Reliance seems to have been placed upon hindsight testimony (taken 10
      years after the events), rather than on documentation of what was known at the
      time when events unfolded. The Report states that "[t]he Committee's charge did
      not include the development of assertions about what should have been done at the
      time,"l(pl:4) yet that is precisely what was done. These comments address just a
      few of the misconceptions we perceive in the Report. They are based on our
      understanding of the state of knowledge--or ignorance--at the time that decisions
      about the safety of the blood supply were made. If we are to avert future threats
      to the blood supply from emerging infectious diseases, a goal that is universally
      embraced, we must learn the lessons the past can teach us, as painful as they may
      be. However, the hazards of judging history in hindsight should be avoided.
      Neither allegations nor opinions should be accepted as facts without critical
      examination and without placement in the context of contemporary knowledge; to
      accept a lesser standard does a great injustice to all who were touched by this
      tragedy.

PMID- 8863783
TI  - Whither the blood products advisory committee?

PMID- 8863784
TI  - Transfusion-transmitted hepatitis G virus following open heart surgery.

PMID- 8863785
TI  - More on the safety of cord blood collection.

PMID- 8863786
TI  - Anti-Vw causing a case of clinically significant hemolytic disease of the
      newborn.

PMID- 8863787
TI  - More on kininogen measurements in platelet concentrates that are white cell (WBC)
      reduced with WBC-reduction filters.

PMID- 8863788
TI  - Alkylation of DNA by the anthracycline, antitumor drugs adriamycin and
      daunomycin.

PMID- 8863789
TI  - 3 alpha-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters:
      novel ligands with high affinity and selectivity at the dopamine transporter.

PMID- 8863790
TI  - Derivatives of the triazoloquinazoline adenosine antagonist (CGS15943) are
      selective for the human A3 receptor subtype.
AB  - The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5
      amine (CGS15943) binds to human A3 receptors with high affinity (Ki = 14 nM),
      while it lacks affinity at rat A3 receptors. Acylated derivatives of the 5-amino
      group and other modifications were prepared in an effort to provide A3 subtype
      selectivity. Affinity was determined in radioligand binding assays at rat brain
      A1 and A2A receptors using [3H]-(R)-PIA ([3H]-(R)-N6-(phenylisopropyl)-adenosine)
      and [3H]CGS 21680 ([3H]-2-[[4-(2-carboxy ethyl)phenyl]ethylaminol]-5'-(N- ethyl-
      carbamoyl)adenosine), respectively. Affinity was determined at cloned human A3
      receptors using [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-(N
      methylcarbamoyl)adenosine). A series of straight chain alkyl amides demonstrated
      that the optimal chain length occurs with the 5-N-propionyl derivative, 3, which
      had a Ki value of 7.7 nM at human A3 receptors, and was 40- and 14-fold selective
      vs rat A1 and A2A receptors, respectively. The 5-N-benzoyl derivative, 10,
      displayed Ki values of 680 and 273 nM at rat A1 and A2A receptors, respectively,
      and 3.0 nM at human A3 receptors. A 5-N-phenylacetyl derivative, 12, was 470-fold
      selective for human A3 vs rat A1 receptors with a Ki value of 0.65 nM. A
      conjugate of Boc-gamma-aminobutyric acid was also prepared but was nonselective.
      Conversion of the 5-amino group of CGS15943 to an oxo function resulted in lower
      affinity but 15-fold selectivity for human A3 receptors.

PMID- 8863791
TI  - Structure-activity relationships of the antimalarial agent artemisinin. 5.
      Analogs of 10-deoxoartemisinin substituted at C-3 and C-9.
AB  - Novel 3- and 9-substituted analogs (4-19) of 10-deoxoartemisinin, 3, were
      prepared from the corresponding known lactones by one-pot reduction with sodium
      borohydride and boron trifluoride etherate. Reproducibility problems associated
      with this heterogeneous reaction were encountered on small reaction scales, and
      thus alternative methodology was sought for this reduction. Conversion of the
      lactones to tetrahydropyrans via the corresponding intermediate lactols was made
      more reproducible using a two-step sequence involving low-temperature reduction
      with diisobutylaluminum hydride followed by deoxygenation with boron trifluoride
      etherate in the presence of triethylsilane. In this manner, 10-deoxoartemisinin
      (3) could be obtained from artemisinin (1) in greater than 95% overall yield. All
      analogs were tested in vitro against W-2 and D-6 strains of Plasmodium
      falciparum. Several of the analogs were much more active than the natural product
      (+)-artemisinin (1) or 10-deoxoartemisinin (3). Conventional structure-activity
      relationships are discussed in relation to the bioassay data.

PMID- 8863792
TI  - Synthesis and structure-activity relationship of pyrazolo[3,4-d]pyrimidines:
      potent and selective adenosine A1 receptor antagonists.
AB  - A series of 12 substituted 1-phenylpyrazolo[3,4-d]pyrimidines were synthesized
      and evaluated for rat brain adenosine A1 and A2a receptor binding affinity.
      Substituents at C-4 and C-6 were varied in order to define these regions in terms
      of molecular recognition by the receptor subtypes. At C-4, the effects of a
      mercapto, methylthio, and amino substituent were evaluated, while at C-6, amides
      with varying alkyl groups extending from the alpha-carbon were examined. This
      study identified both potent and selective adenosine A1 receptor antagonists. The
      most potent of the 12 compounds was alpha-[(4-amino-1-phenylpyrazolo[3,4
      d]pyrimidin-6-yl)thio]hexanamide (14); with an A1 Ki of 0.939 nM and an A2a Ki of
      88.3 nM, this compound is 94-fold A1 selective. The most selective of the 12
      compounds was alpha-[[4-(methylthio)-1-phenylpyrazolo[3,4-d]pyrimidin-6
      yl]thio]hex anamide (10); with an A1 Ki of 6.81 nM and an A2a Ki > 40 000 nM,
      this compound is > 5900-fold A1 selective. The structure-activity relationships
      for the complete series has identified discrete structural differences between
      the A1 and A2a receptors with respect to the binding of pyrazolo[3,4
      d]pyrimidines. This study resulted in prediction that increased A1 affinity could
      be achieved by incorporation of NH-alkyl substituents at C-4. This was confirmed
      by synthesis of alpha-[[4-(methylamino)-1-phenylpyrazolo[3,4-d]pyrimidin-6
      yl]thiol] hexanamide (15) which was found to have an A1 Ki of 0.745 nM.

PMID- 8863793
TI  - Inactivation of S-adenosyl-L-homocysteine hydrolase by amide and ester
      derivatives of adenosine-5'-carboxylic acid.
AB  - S-Adenosyl-L-homocysteine (AdoHcy) hydrolase has been shown to have (5'/6')
      hydrolytic activity with vinyl (5') or homovinyl (6') halides derived from
      adenosine (Ado). This hydrolytic activity is independent of its 3'-oxidative
      activity. The vinyl (or homovinyl) halides are converted into 5'(or 6')
      carboxaldehydes by the hydrolytic activity of the enzyme, and inactivation occurs
      via the oxidative activity. Amide and ester derivatives of Ado-5'-carboxylic acid
      were prepared to further probe the hydrolytic capability of AdoHcy hydrolase. The
      oxidative activity (but not the hydrolytic activity) is involved in the mechanism
      of inhibition of the enzyme by the ester and amide derivatives of Ado-5'
      carboxylic acid, in contrast to the inactivation of this enzyme by adenosine
      derived vinyl or homovinyl halide analogues during which both activities are
      manifested.

PMID- 8863794
TI  - Understanding the mechanism of sweet taste: synthesis of ultrapotent
      guanidinoacetic acid photoaffinity labeling reagents.
AB  - Azido-functionalized analogs of potently sweet guanidinoacetic acids have been
      synthesized for use as sweetener receptor photoaffinity labeling reagents. These
      compounds have been synthesized using readily available starting materials. One
      of the azido-labeled guanidinoacetic acids has been evaluated in an
      electrophysiological model in the Rhesus monkey. We found that the photoaffinity
      labeling reagent caused irreversible inhibition in electrophysiological response
      to sweeteners upon exposure of the monkey tongue to a combination of the reagent
      and UV light.

PMID- 8863795
TI  - Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with
      improved in vivo antiviral activity.
AB  - We have been investigating the potential of a new class of antiviral compounds.
      These peptidomimetic derivatives prevent association of the two subunits of
      herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for
      efficient replication of viral DNA. The compounds disclosed in this paper build
      on our previously published work. Structure-activity studies reveal beneficial
      modifications that result in improved antiviral potency in cell culture in a
      murine ocular model of HSV-induced keratitis. These modifications include a
      stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two
      ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus.
      These three modifications led to the preparation of BILD 1351, our most potent
      antiherpetic agent containing a ureido N-terminus. Incorporation of the C
      terminal modification into our inhibitor series based on a
      (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more
      potent antiviral compound than our previously published best compound, BILD 1263.

PMID- 8863796
TI  - Structure-activity relationships for inhibition of inosine monophosphate
      dehydrogenase by nuclear variants of mycophenolic acid.
AB  - Structure-activity relationships in the region of the phthalide ring of the
      inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been
      explored. Replacement of the lactone ring with other cyclic moieties resulted in
      loss of potency, especially for larger groups. Replacement of the ring by acyclic
      substituents also indicated a strong sensitivity to steric bulk. A phenolic
      hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be
      essential for high potency. The aromatic methyl group was essential for activity;
      the methoxyl group could be replaced by ethyl to give a compound with 2-4 times
      the potency of mycophenolic acid in vitro and in vivo.

PMID- 8863797
TI  - Hydroxamic acid-based bisubstrate analog inhibitors of Ras farnesyl protein
      transferase.
AB  - The rational design, synthesis, and activity of novel, hydroxamic acid-based,
      collective bisubstrate analog inhibitors of farnesyl protein transferase (FPT) is
      described. This class of compounds differ structurally from the conventional FPT
      inhibitors by being non-sulfhydryl and by being bisubstrate based rather than
      peptide or FPP derived inhibitors. Whereas replacement of the sulfhydryl group of
      tetrapeptide CVLS (I50 = 1 microM) by an N-methylhydroxamic acid had a
      deleterious effect (10, I50 > 360 microM), moderate inhibition was realized with
      16 (I50 = 42.5 microM), a bisubstrate analog involving anchorage of farnesyl and
      tripeptide groups by a hydroxamic acid-embedded linker. Starting from 16, a 1
      order of magnitude improvement in in vitro potency was obtained by optimization
      of the linker (20, I50 = 4.35 microM). An additional 13-fold enhancement was
      achieved by substituting the tripeptide moiety VLS in 20 by VVM (23, I50 = 0.33
      microM). The dependence of these inhibitors on their peptide and farnesyl
      subunits is suggestive of their bisubstrate nature. Compound 23 (I50 = 0.33
      microM) is 2 orders of magnitude better in activity compared to the initial lead
      16 [I50 = 42.5 microM) and is effective in blocking prenylation of protein in
      whole cells including p21ras.

PMID- 8863798
TI  - 2-alkenyl and 2-alkyl derivatives of adenosine and adenosine-5'-N-ethyluronamide:
      different affinity and selectivity of E- and Z-diastereomers at A2A adenosine
      receptors.
AB  - A series of new 2-(ar)alkenyl, both Z- and E-diastereomers, and 2-alkyl
      derivatives of adenosine-5'-N-ethyluronamide (NECA) and adenosine were
      synthesized and evaluated for their interaction with the A1 and A2A adeosine
      receptors, to better understand the conformational requirements of the receptor
      area interacting with the substituents in the 2- and 5'-positions. Partial
      reduction of the triple bond in 2-alkynyl derivatives of NECA led to compounds
      whose activity at the A2A receptor subtype was related to Z-E-isomerism, the E
      diastereomers being more potent and selective than the Z-ones. Saturation of the
      side chain markedly reduced compound affinity at adenosine receptors.
      Specifically, compounds bearing an (E)-alkenyl chain, while maintaining the same
      affinity at A2A receptors as the corresponding alknyl derivatives, showed an
      increase in A2A vs A1 selectivity. Hence, the new nucleosides (E)-2-hexenylNECA
      (12a) and (E)-2-(phenylpentenyl)NECA (12b) exhibited both high A2A receptor
      affinity (Ki = 1.6 and 3.5 nM, respectively) and A2A vs A1 selectivity (157- and
      290-fold, respectively). Moreover, 12a displayed potent antiaggregatory activity,
      similar to that of the reference compound NECA. Comparison between NECA and
      adenosine derivatives further demonstrated that the 5'-ethylcarboxamido group is
      critical for the A2A affinity. These studies indicated that the orientation of
      the substituent in the 2-position and the nature of the 5'-group in adenosine
      derivatives are critical to achieve high affinity and selectivity at the A2A
      adenosine receptor subtype.

PMID- 8863799
TI  - Neurosteroid analogues. 4. The effect of methyl substitution at the C-5 and C-10
      positions of neurosteroids on electrophysiological activity at GABAA receptors.
AB  - A series of analogues of the neuroactive steroids 3 alpha-hydroxy-5 alpha-pregnan
      20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one were studied to elucidate the
      mode of binding of 5 alpha-and 5 beta-reduced steroids to steroid binding sites
      on GABAA receptors. Analogues which were either 3 alpha-hydroxy-20-ketosteroids
      or 3 alpha-hydroxysteroid-17 beta-carbonitriles and which contained various
      methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations
      utilized whole-cell patch clamp electrophysiological methods carried out on
      cultured rat hippocampal neurons, and the results obtained with the rigid 17 beta
      carbonitrile analogs were analyzed using molecular modeling methods. The
      molecular modeling results provide a rationale for the observation that the
      configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic
      potency than the configuration of the A,B ring fusion at C-5. The
      electrophysiological results identify steric restrictions for the space that can
      be occupied in 5 alpha- and 5 beta-reduced steroid modulators of GABAA receptors
      in the regions of space proximate to the steroid C-5, C-10, and possibly C-4
      positions. This information is useful for the development of nonsteroidal
      analogues that can modulate GABAA receptors via interactions at steroid binding
      sites.

PMID- 8863800
TI  - Affinity for dopamine D2, D3, and D4 receptors of 2-aminotetralins. Relevance of
      D2 agonist binding for determination of receptor subtype selectivity.
AB  - A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on
      the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were
      prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4
      receptors. Some members of this series were prepared in former studies, but were
      never tested in vitro with single receptor subtypes, and these were examined
      again. None of the tested 2-aminotetralins showed high affinity for the dopamine
      D4 receptor. However, a number of the 2-aminotetralins showed high affinity for
      both the D2 and the D3 DA receptors, as exemplified by compounds 11-15 and 21-26,
      while some had a reasonable selectivity for the DA D3 receptors. The affinities
      of the 2-aminotetralins for the D21, receptor depended on the type of radioligand
      (agonist or antagonist) used. The agonist affinity data, obtained by using the
      agonist ligand [3H]N-0437, are thought to be more relevant for calculating DA
      receptor subtype selectivity.

PMID- 8863801
TI  - Synthesis, resolution, and preliminary evaluation of trans-2-amino-6(5)-hydroxy-1
      phenyl-2,3-dihydro-1H-indenes and related derivatives as dopamine receptors
      ligands.
AB  - The present work reports the synthesis of enantiomeric pairs of the trans-2-amino
      6-hydroxy-1-phenyl-2,3-dihydro-1H-indene [(+)-14a, (-)-14a] and trans-2-amino-5
      hydroxy-1-phenyl-2,3-dihydro-1 H-indene [(+)-14b, (-)-14b] and their N,N-di-n
      propyl [(+)-and (-)-15a,b], N-methyl-N-allyl [(+)-and (-)-16a,b], and N-methyl-N
      n-propyl [(+) and (-)-17a,b] derivatives obtained by a combination of
      stereospecific reactions and optical resolution. The new compounds were evaluated
      for their affinity at the dopamine D1 and D2 receptors. The amines (+)- and (-)
      14a, incorporating the D1 pharmacophore 2-phenyl-2-(3-hydroxyphenyl)ethylamine in
      a trans extended conformation, and their derivatives displayed D1 and D2 affinity
      in the nanomolar range. On the other hand, the enantiomers (+)- and (-)-14b, (+)-
      and (-)-15b displayed high affinity and selectivity for the D1 receptor. In a
      preliminary behavioral study on rats (+)-14b, and to a greater extent (+)-15b,
      promoted episodes of intense grooming, thus indicating that they act as central
      D1 agonists. The trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1H-indenes (+)-14b
      and (+)-15b represent selective D1 agonists lacking a catechol group, which
      should meet the prerequisites for a central nervous system penetration.

PMID- 8863802
TI  - Synthesis, molecular modeling, and K+ channel-blocking activity of dequalinium
      analogues having semirigid linkers.
AB  - Dequalinium [1,1'-(decane-1, 10-diyl)bis(2-methyl-4-aminoquinolinium)] is an
      effective blocker of the small conductance Ca2(+)-activated K+ channel. It has
      been shown that the number of methylene groups in the alkyl chain linking the two
      quinolinium rings of this type of molecule is not critical for activity. To
      further investigate the role of the linker, analogues of dequalinium have been
      synthesized, in which the alkyl chain has been replaced by CH2XCH2 where X is a
      rigid or semirigid group containing aromatic rings. The compounds have been
      tested for blockade of the slow after-hyperpolarization on rat sympathetic
      neurons. The most potent compounds have X = phenanthryl, fluorenyl, cis-stilbene,
      and C6H4(CH2)nC6H4, where n = 0-4. The conformational preferences of the
      compounds were investigated using the XED/COSMIC molecular modeling system.
      Although there is some dependence of the potency of the analogue on the
      conformational properties of the linker (X), overall, X groups having substantial
      structural differences are tolerated. It seems that X provides a support for the
      two quinolinium groups and does not interact with the channel directly. The
      intramolecular separation between the quinolinium rings, which is provided by
      rigid groups X, is not critical for activity; this may be attributed to the
      residual conformational mobility of the heterocycles and to the extensive
      delocalization of the positive charge. These two factors may permit favorable
      contacts between the quinolinium groups and the channel over a range of
      intramolecular separations.

PMID- 8863803
TI  - Novel potent sigma 1 ligands: N-[omega-(tetralin-1-yl)alkyl]piperidine
      derivatives.
AB  - A series of substituted N-[(tetralin-1-yl)alkyl]piperidines and a number of
      related N-di-n-propyl-[(tetralin-1-yl)alkyl]amines were prepared. Structural
      modifications such as piperidine substitutions, intermediate chain lengthening,
      and the nature of the aromatic ring were explored in order to identify structural
      requirements for selective sigma 1 affinity. They were tested in radioligand
      binding assays on sigma 1, 5-HT1A and 5-HT2 serotonergic, PCP (phencyclidine),
      and D-2 dopaminergic receptors. Almost all the compounds reported here showed a
      high to superpotent sigma 1 affinity, and some compounds also demonstrated a
      widespread selectivity over the other receptors. In [3H]-(+)-pentazocine binding,
      3,3-dimethyl-1-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n- propyl]
      piperidine (24) and 3,3-dimethyl-1-[4-(1,2,3,4-tetrahydronaphthalen-1-yl)-n-
      butyl]piperidine (26) reached the lowest Ki values (0.4 and 0.8 nM,
      respectively); compound 24 also demonstrated a considerable PCP affinity (Ki =
      34.2 nM), whereas compound 26 was suitably selective. Furthermore the presence of
      a 4-benzyl substituent on the piperidine ring (compound 16, Ki = 3.9 nM on sigma
      1 sites) caused an increase in 5-HT1A affinity (Ki < 0.14 nM).

PMID- 8863804
TI  - Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse
      transcriptase inhibitors. 2. Synthesis and further structure-activity
      relationship studies of PETT analogs.
AB  - Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new
      series of non-nucleoside inhibitors of HIV-1 RT. Structure-activity relationship
      studies of this class of compounds resulted in the identification of N-[2-(2
      pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine;
      LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in
      phase one clinical trials for potential use in the treatment of AIDS. Extension
      of these structure-activity relationship studies to identify additional compounds
      in this series with improved properties is ongoing. A part of this work is
      described here. Replacement of the two aromatic moieties of the PETT compounds by
      various substituted or unsubstituted heteroaromatic rings was investigated. In
      addition, the effects of multiple substitution in the phenyl ring were also
      studied. The antiviral activities were determined on wild-type and constructed
      mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof,
      Ile100 and Cys181, in cell culture assays. Some selected compounds were
      determined on double-mutant viruses, HIV-1 (Ile 100/Asn103) and HIV-1
      (Ile100/Cys181). A number of highly potent analogs were synthesized. These
      compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell
      culture, these agents inhibited wild-type HIV-1 with ED50's between 1 and 5 nM in
      MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100)
      with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's
      between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100)
      with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3
      and 20 nM.

PMID- 8863805
TI  - Molecular basis of peripheral vs central benzodiazepine receptor selectivity in a
      new class of peripheral benzodiazepine receptor ligands related to alpidem.
AB  - Alpidem (1), the anxiolytic imidazopyridine, has nanomolar binding affinity for
      both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine
      receptor (PBR). A novel class of PBR ligands related to alpidem has been designed
      by comparing the interaction models of alpidem with PBR and CBR. Several
      compounds in this class have shown high selectivity for PBR vs CBR, and the
      selectivity has been discussed in terms of interaction models. The binding
      behavior of the three selected compounds was extensively studied by competition
      and saturation assays, and the results suggest that they are capable of
      recognizing two sites labeled by [3H]PK11195. The molecular structure of one of
      the most active compounds (4e) has been determined by X-ray diffraction and
      compared with that of alpidem. Molecular modeling studies suggest that the
      bioactive conformation of 4e is likely to be very similar to the conformation
      found in the crystal.

PMID- 8863806
TI  - 3-amino-3,4-dihydro-2H-1-benzopyran derivatives as 5-HT1A receptor ligands and
      potential anxiolytic agents. 2. Synthesis and quantitative structure-activity
      relationship studies of spiro[pyrrolidine- and piperidine-2,3'(2'H)-benzopyrans].
AB  - In continuation of our work on 3-amino-3,4-dihydro-2H-1-benzopyran derivatives
      with high affinity for 5-HT1A receptors, we have prepared rigid spirobenzopyran
      analogues designed from the pharmacophore models of Mellin and selected via a
      quantitative structure-activity relationship approach mainly based on similarity
      indices. A series of spiro[pyrrolidine- and piperidine-2,3'(2'H)-benzopyrans]
      with various substitutions on the aromatic ring as well as on the extracyclic
      spiranic nitrogen atom were then synthesized and evaluated for their serotonergic
      and dopaminergic activities. Good correlation between the predicted and the
      experimental binding values was observed with an average difference of 0.2 unit
      on log(IC50). Affinities for the 5-HT1A receptors were in the nanomolar range for
      the best compounds ((+)-11a,23) with a high selectivity versus other 5-HT (5
      HT1B, 5-HT2, 5-HT3) or dopamine (D1, D2) receptor subtypes. As for the 3-amino
      3,4-dihydro-2H-1-benzopyran series, the dextrorotatory enantiomer (+)-11a showed
      better affinity and selectivity for 5-HT1A receptors than its levorotatory
      analogue (-)-11a. Compound (+)-11a proved in vitro to be a full agonist and in
      vivo to be active in various comportmental tests predictive of psychotropic
      activity, such as the forced swim test and the tail suspension test, and is
      currently under complementary investigations.

PMID- 8863807
TI  - HIV protease inhibitory bis-benzamide cyclic ureas: a quantitative structure
      activity relationship analysis.
AB  - A series of N,N'-disubstituted cyclic urea 3-benzamides has been synthesized and
      evaluated for HIV protease inhibition and antiviral activity. Some of these
      benzamides have been shown to be potent inhibitors of HIV protease with Ki <
      0.050 nM and IC90 < 20 nM for viral replication and, as such, may be useful in
      the treatment of AIDS. The synthesis and quantitative structure-activity
      relationship for this benzamide series will be discussed.

PMID- 8863808
TI  - Biophysical characterization of zinc ejection from HIV nucleocapsid protein by
      anti-HIV 2,2'-dithiobis[benzamides] and benzisothiazolones.
AB  - HIV nucleocapsid protein (NCp7) has been suggested as a possible target for 2,2'
      dithiobis-[benzamide] and benzisothiazolone agents that inhibit viral replication
      in infected cells (Rice et al. Science 1995, 270, 1194-1197). The solution
      behavior of these compounds and the mechanistic events leading to removal of Zn
      from HIV nucleocapsid protein in vitro has been studied by electrospray
      ionization mass spectrometry, 500 MHz one- and two-dimensional nuclear magnetic
      resonance spectroscopy, and circular dichroism spectroscopy. We demonstrate that
      (1) Zn ejection is accompanied by formation of covalent complexes formed between
      the 2,2'-dithiobis[benzamide] monomers and Cys residues of Zn-depleted NCp7, (2)
      the rate of Zn ejection is faster for the C-terminal Zn finger and slower for the
      N-terminal finger, (3) Zn ejection results in a loss of structural integrity of
      the NCp7 protein, and (4) there is no appreciable interaction between a
      nonreactive isostere of the lead 2,2'-dithiobis[benzamide] and NCp7 in buffered
      aqueous solution. These findings are discussed in terms of the mechanism of
      action of Zn ejection by aromatic 2,2'-dithiobis[benzamides].

PMID- 8863809
TI  - Chemistry of the pyrrolo[1,2-alpha]benzimidazole antitumor agents: influence of
      the 7-substituent on the ability to alkylate DNA and inhibit topoisomerase II.
AB  - This study addresses the influence the 7-substituent on the cytotoxicity of
      pyrrolo[1,2-alpha]-benzimidazole quinones possessing a 6-aziridinyl group (PBIs)
      and a 6-acetamido group (APBIs). Reduction of a PBI to the aziridinyl
      hydroquinone results in both nucleophile trapping (alkylation) and 1,5
      sigmatropic shift reactions. The latter process is essentially an internal redox
      reaction wherein the hydroquinone causes reductive opening of the aziridinyl
      ring. The 7-substituent controls the fate of the aziridinyl ring by means of
      steric and electronic effects. An electron-rich 7-substituent favors the 1,5
      sigmatropic shift reaction. If the 7-substituent distorts the 6-aziridinyl group
      from the conformation required for the 1,5-sigmatropic shift, then nucleophile
      trapping occurs. The 7-methyl substituent results in significant nucleophilic
      trapping, and the 7-unsubstituted and 7-methoxy substituents favor the 1,5
      sigmatropic reaction. Thus, the 7-methyl PBIs show the most cytotoxicity of the
      analogues studied. The APBIs are cytotoxic only as quinones, and reduction to the
      hydroquinone results in loss of activity. Consistent with this observation, the
      change from 7-methyl to the more electron-rich 7-methoxy results in a substantial
      loss of APBI cytotoxicity as well as decreased topoisomerase II inhibition. The
      mechanism of inhibition is thought to involve the interacalation of only electron
      deficient APBIs into DNA.

PMID- 8863810
TI  - Molecular modeling studies of "flap up" mannosyl cation mimics.
AB  - The importance of inhibitors of glycosidases as therapeutic agents for viral,
      proliferative, and metabolic diseases is being increasingly recognised. Several
      years ago we reported that the activities of mannosidase inhibitors may be
      explained in terms of their similarity to the mannosyl cation intermediate
      postulated to form during the enzyme-catalyzed processing of oligosaccharide
      substrates. Recently, the validity of this model has been called in to question
      by some authors. We report recent molecular modeling studies undertaken to
      clarify this apparent contradiction. Mannostatin can indeed bind in a fashion
      which bears a close similarity to the mannosyl cation. Moreover we have shown
      that (-)-mannostatin is not able to adopt a similar binding mode to that of the
      mannosyl cation. As additional proof, Farr et al. have synthesized a
      trihydroxycyclopentylamine as a direct mimic of our mannosyl cation model.
      Satisfyingly, this compound shows potent inhibition of Jack Bean alpha
      mannosidase, as predicted by the model. The inactivity of
      aminotrihydroxyhexahydro-1H-azepine against mannosidases can be explained in
      terms of the relative energies of the axial versus equatorial conformations of
      the critical hexahydroazepine ring substituents.

PMID- 8863811
TI  - Synthesis and evaluation of pregnane derivatives as inhibitors of human
      testicular 17 alpha-hydroxylase/C17,20-lyase.
AB  - The pregnene derivatives with modifications at the 17,20-side chain and D-ring
      were synthesized and evaluated as inhibitors of human testicular 17 alpha
      hydroxylase/C17,20-lyase. The results demonstrate that compounds which have 20
      substituents with moderate to strong dipole properties, such as 20-oxime (3, 20),
      20 beta-ol (24, 30), and 20 beta-carboxaldehyde (27), are potent inhibitors of
      this enzyme complex. The 20-substituents with hydrophobic property were devoid of
      inhibitory activity, e.g., the dimethylhydrazones 8 and 9. The 16-ene together
      with 20-oxime (20) showed the most potent inhibition of this enzyme complex,
      whereas 17(20)-ene modification as in 17(20)-ene-20-carbonitrile (14) did not
      increase activity in comparison to the 20 beta-carbonitrile (16). The bioisotere
      of 27 with 20-aza (19) also reduced the inhibitory activity. The results showed
      that isomeric configurations at the 20-position of some steroidal compounds are
      important factors which influence the potency of the inhibition significantly
      (e.g., 20 beta-ols 24 and 30 were 3-5-fold more potent than 20 alpha-ols 23 and
      29). As expected, some compounds based on the pregn-5-en-3 beta-ol skeleton,
      which is similar to the natural substrate of human testicular 17 alpha
      hydroxylase/C17,20-lyase in A- and B-rings, showed more potent inhibition than
      similar compounds which are based on the pregn-4-en-3-one skeleton (e.g., 23-25
      compared to 29-31). These results suggest that A- and B-rings make significant
      contributions to the binding of these steroidal compounds to the 17 alpha
      hydroxylase and C17,20-lyase. In comparison to ketoconazole, a nonsteroidal
      inhibitor of 17 alpha-hydroxylase and C17,20-lyase which has been used in the
      treatment of prostatic cancer, the steroidal compounds 20, 24, and 27 demonstrate
      more potent inhibition for this enzyme complex. These inhibitors warrant further
      investigation in biological systems. The structural features of these compounds
      may serve as leads in the design of new inhibitors.

PMID- 8863812
TI  - Design and synthesis of histidine analogues of folic acid and methotrexate as
      potential folylpolyglutamate synthetase inhibitors.
AB  - Folypolyglutamate synthetase (FPGS) is responsible for the conversion of
      naturally occurring folates and antifolates to their poly-gama-glutamyl
      derivatives, which are the forms required for intracellular retention of folates
      and are also the preferred substrates (cofactors) for most folate-dependent
      enzymes. Folate and methotrexate analogues 6 and 4, with L-histidine in place of
      L-glutamate, were designed and synthesized as potential FPGS inhibitors. Target
      compound 5, the N tau-(carboxymethyl)-L-histidine derivative of 4, was also
      prepared. Compounds 4 and 5 inhibited the growth of L1210 cells (IC50 values:
      0.091 and 0.15 microM, respectively) and were potent inhibitors of L1210
      dihydrofolate reductase. No significant inhibition of FPGS by 4, 5, or 6 was
      observed at the high pH of the standard enzyme assay. This could be the
      consequence of a lack of protonation of the basic side chains, which is likely to
      be required for FPGS inhibitory activity. The observed cytotoxicity indicates
      that partial protonation of the imidazole ring permits cellular uptake of the
      analogues.

PMID- 8863813
TI  - Activation of N-methyl-D-aspartate receptors by glycine: role of an aspartate
      residue in the M3-M4 loop of the NR1 subunit.
AB  - Glutamate and glycine are coagonists that act at distinct sites to activate N
      methyl-D-aspartate (NMDA) receptors. In the NR1 subunit of the NMDA receptor,
      mutation of D732 to glutamate (D732E), asparagine (D732N), alanine (D732A), or
      glycine (D732G) reduced the potency of glycine by > 4000-fold, but these
      mutations had no effect on sensitivity to glutamate. Mutations at NR1(D732) also
      changed sensitivity to the glycine-site agonists D-serine and D-alanine, reducing
      the potencies and, in some cases, the efficacies of these compounds. Thus, D
      serine was a full agonist at the glycine site of receptors containing NR1(D732N)
      and NR1(D732A), a partial agonist at receptors containing NR1(D732G), and a
      competitive antagonist at receptors containing NR1(D732). Mutations at NR1(D732)
      had no effect or produced an increase in sensitivity to the glycine-site
      antagonists 6,7-dichloroquinoxaline-2,3-dione and 5,7-dichlorokynurenic acid.
      These mutations did not affect the reversal potential, voltage-dependent block by
      extracellular Mg2+, block by ifenprodil, or stimulation by spermine at NR1/NR2B
      receptors. NR2 subunits containing mutations at NR2A(D731) and NR2B(D732), which
      correspond to NR1(D732), did not produce functional receptors when coexpressed
      with NR1. Residue D732 in NR1 may be close to a glycine binding site on the NMDA
      receptor and may directly affect the properties of this site or be critical for
      coupling of glycine binding to channel activation.

PMID- 8863814
TI  - Identification and characterization of novel somatostatin antagonists.
AB  - The study of the five somatostatin receptor subtypes (SSTx, where x is the
      subtype number) has been hampered by the lack of high affinity antagonists.
      Potent and selective antagonists would increase our understanding of SST
      structure, function, and regulation. In this study, the identification of novel
      disulfide-linked cyclic octapeptide antagonists of somatostatin is described. The
      antagonists contain a core structure of a DL-cysteine pair at positions 2 and 7
      of the peptides. Substitution of a D-cysteine at position 2 with an L-cysteine
      converts the full antagonist into a full agonist. All somatostatin receptor
      subtypes are coupled to inhibition of adenylate cyclase. The functional
      properties of these peptides have been determined in radioligand binding assays,
      in functional coupling of the SST2 subtype to yeast pheromone response pathway,
      and in cAMP accumulations. One peptide antagonist [Ac-4-NO2-Phe-c(D-Cys-Tyr-D-Trp
      Lys-Thr-Cys)-D-Tyr-NH2] displays a binding affinity to SST2 comparable with that
      observed for the native hormone (Ki = 0.2 nM) and reverses somatostatin-mediated
      inhibition of cAMP accumulation in rat somatomammotroph GH4C1 cells, cells
      transfected with the SST2 and SST5 subtypes, as well as somatostatin-stimulated
      growth of yeast cells expressing the SST2 subtype. This class of somatostatin
      antagonists, which are the first to be described, should be useful for
      determination of somatostatin's diverse functions in vivo and in vitro.

PMID- 8863815
TI  - Agonist binding and protein kinase C activation stimulate phosphorylation of the
      gastrin-releasing peptide receptor at distinct sites.
AB  - Gastrin-releasing peptide and other bombesin-like peptides stimulate secretion,
      cell proliferation, and smooth muscle contraction via a family of G protein
      coupled receptors that activate phospholipase C. Second messenger formation by
      one of these receptors, called BR1, is rapidly desensitized after treatment of
      cells with either agonists or the protein kinase C activator 12-O
      tetradecanoylphorbol-13-acetate (TPA). To determine whether receptor
      phosphorylation was involved in BR1 desensitization, we generated antibodies to a
      peptide corresponding to a unique sequence within the COOH terminus of this
      receptor. One antibody (BR1-517) immunoprecipitated 60% of the solubilized [125I
      Tyr4]bombesin/receptor complex prepared from either Swiss 3T3 fibroblasts or CHO
      K1 cells transfected to express high levels of mouse BR1 (CHO-mBR1). Furthermore,
      immunoprecipitation of photoaffinity-labeled receptors yielded the expected 87
      kDa radiolabeled band on gel electrophoresis. Phosphorylation of this
      immunoprecipitated receptor protein was markedly stimulated when
      [32P]orthophosphate-labeled Swiss 3T3 cells or CHO-mBR1 cells were treated with
      100 nM bombesin for 5 min. 32PO4 incorporation into immunoprecipitated receptor
      was detectable after 2 min and maximal after 15 min of bombesin treatment.
      Phosphoamino acid analysis showed 32P labeling of serine and theonine but not
      tyrosine residues. Pretreatment of CHO-mBR1 cells with 100 nM TPA for 30 min also
      desensitized bombesin stimulation of inositol-1,4,5-trisphosphate formation.
      However, TPA did not increase 32PO4 incorporation into the immunoprecipitated
      receptor, although protein kinase C inhibition potentiated bombesin-induced
      receptor phosphorylation. Subsequent studies showed that TPA did stimulate
      receptor phosphorylation, but the antibody did not recognize this phosphorylated
      state of the receptor. Thus, TPA decreased the efficiency of receptor
      immunoprecipitation, and subsequent incubation of receptor with alkaline
      phosphatase reversed this TPA inhibition. The differential specificity of the
      antibody for various phosphorylated forms of BR1 demonstrates that agonist
      induced and TPA-induced phosphorylations of the receptor occur at distinct sites.

PMID- 8863816
TI  - Expression of human NAD(P)H: quinone oxidoreductase (DT-diaphorase) in Chinese
      hamster ovary cells: effect on the toxicity of antitumor quinones.
AB  - Previous studies have indicated that NAD(P)H: quinone oxidoreductase [DT
      diaphorase (NQO1)] plays an important role in the bioreductive activation of
      quinone-containing antitumor agents. Although these studies demonstrated that
      purified NQO1 can reduce these compounds in vitro, the importance of NQO1 in the
      intracellular activation of quinone-containing antitumor agents remains
      controversial. In our study, we transfected human NQO1 into Chinese hamster ovary
      cells that do not normally express NQO1 activity and obtained stable clones that
      expressed NQO1 activity of 19-3527 nmol of 2,6-dichlorophenolindophenol
      reduced/min/mg of protein. The level of NQO1 expression correlated with an
      increased killing by streptonigrin, EO9 (3-hydroxymethyl-5-aziridinyl-1-methyl-2
      (1H-indole-4,7-dione)-propen ol), and 2,5-diaziridinyl-3,6-dimethyl-1,4
      benzoquinone, but mitomycin C sensitivity was independent of this activity. NQO1
      expression also led to a slight decrease in the sensitivity of cells to
      menadione. Our data demonstrate that compounds that are efficient substrates for
      NQO1 in vitro are also bioactivated in cultured mammalian cells when they are
      transfected with human NQO1. These results are consistent with the relative
      abilities of mitomycin C, streptonigrin, EO9, and 2,5-diaziridinyl-3,6-dimethyl
      1,4-benzoquinone to serve as substrates for bioreduction by human NQO1, and show
      that NQO1 levels are not necessarily predictive in terms of sensitivity to
      mitomycin C.

PMID- 8863817
TI  - Structural determinants of substrates for the prostaglandin transporter PGT.
AB  - We recently identified a broadly expressed transporter, PGT, that transports
      primarily prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). In the current
      study, we examined the structural determinants of potential PGT substrates in
      detail. Rat PGT was transiently expressed in HeLa cells, the timed uptake of
      tracer PGE2 was determined in the presence of various concentrations of unlabeled
      prostanoids; and the resulting inhibitory constants (Ki) were determined by curve
      fitting. PGE2 and PGF2 alpha, both known to be transported, had similar
      affinities for PGT (Ki = 49-50 nM). The strongest interaction (Ki = 13-19 nM) was
      obtained with prostanoids lacking the 9- or 11-position oxygen groups. A
      relatively high affinity was also obtained for the bicycloendoperoxides U44069,
      PGH2, and U46619 (Ki = 29-39 nM). However, a radioactive representative from this
      group, U46619, was not transported. Structural modifications that produced a
      moderately reduced affinity relative to that of PGE2 (Ki = 56-286 nM) included
      reduction in C5 = C6, the addition of a benzene group at position C18, and
      isomerization at the C8 position. In complementary studies, tracer isoprostane B
      iso-PGF2 alpha was found to be transported at approximately 13% the rate of
      tracer PGE2. Substantially weaker interaction (Ki = > 700 nM) was seen when the 1
      position COO- anionic group was neutralized or when the 15(S)-OH group was
      changed to 15(R)-OH or to 15-keto. These results with the cloned rat PGT are very
      similar to those previously reported in the in vitro perfused rat lung and
      indicate that PGT probably represents the predominant route by which certain
      prostanoids, including F2 isoprostanes, are transported across plasma membranes.

PMID- 8863818
TI  - Enhanced angiotensin receptor type 1 mRNA degradation and induction of
      polyribosomal mRNA binding proteins by angiotensin II in vascular smooth muscle
      cells.
AB  - Stimulation of cultured rat thoracic aorta vascular smooth muscle cells (VSMCs)
      with 100 nM angiotensin II (Ang II) reduces angiotensin receptor type 1 (AT1-R)
      gene expression. mRNA levels are reduced to approximately 30% of control levels 4
      hr after the addition of Ang II to the culture medium. The loss of mRNA remains
      sustained for up to 24 hr after the addition of Ang II. The half-life of the AT1
      R mRNA is approximately 2 hr in cells treated with a single dose of 100 nM Ang
      II. This represents a 3-fold reduction from its half-life of 6 hr in
      nonstimulated cells, as assessed by treatment with 5,6-dichlorobenzimidazole or
      actinomycin D to block transcription. Thus, the AT1-R mRNA is moderately unstable
      in VSMC and destabilized further by treatment with Ang II. Ang II-induced AT1-R
      mRNA destabilization is prevented by pretreatment with transcriptional inhibitors
      or the protein synthesis inhibitor cycloheximide, suggesting that Ang II-induced
      AT1-R mRNA destabilization requires the induction of an unknown factor or factors
      that are postulated to mediate this effect. AT1-R mRNA levels decrease more
      rapidly in vitro from a polyribosomal fraction isolated from VSMC exposed for 2
      hr to 100 nM Ang II compared with that from vehicle-treated cells, suggesting
      that polyribosomal-associated AT1-R mRNA is at least one site of action for the
      mRNA destabilization effect of Ang II. Ang II stimulation induces a complex of
      polyribosomal proteins that bind specifically in the distal 350 bases of the AT1
      R mRNA. Regulation of mRNA stability accounts in part for modulation of AT1-R
      gene expression by Ang II in VSMCs, and Ang II-induced AT1-R mRNA polyribosomal
      binding proteins are associated with this phenomenon.

PMID- 8863819
TI  - 5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the
      serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D
      receptors.
AB  - The serotonergic system controls the activity of neurotransmissions involved in
      numerous physiological functions. It is also thought to be crucially implicated
      in various pathologies, including psychiatric disorders such as depression,
      anxiety, and aggressiveness. The properties of 5-hydroxytryptamine (5-HT)
      moduline, a novel endogenous peptide, have been tested in vitro and in vivo.
      Binding studies have shown that the peptide specifically interacts with 5-HT1B/1D
      receptors via a noncompetitive mechanism corresponding to a high apparent
      affinity (EC50 = 10(10) M). The interaction was shown in rat and guinea pig brain
      tissues and in cells transfected with either 5-HT1B or 5-HT1D beta receptor gene.
      [3H]5-HT-moduline binds to a single population of sites in mammalian brain (Kd =
      0.4 nM in rat, Kd = 0.8 nM in guinea pig) as well as in transfected cells
      expressing the 5-HT1B or the 5-HT1D beta receptors (Kd = 0.2 and 0.6 nM,
      respectively). Furthermore, the binding is clearly specific of the LSAL sequence.
      Autoradiographic studies showed an heterogeneous brain distribution of this site.
      The interaction of 5-HT-moduline with the 5-HT1B/1D receptor corresponds to a
      decrease in the functional activity of the receptor (i.e., a decrease in the
      inhibitory effect of a 5-HT1B agonist on the evoked release of [3H]5-HT from
      synaptosomal preparation). It was also shown that 5-HT-moduline possess an in
      vivo effect in the social interaction test in mouse. Finally, it was demonstrated
      that 5-HT-moduline was released from brain synaptosomal preparation by a
      K+/Ca(2+)-dependent mechanism. In conclusion, 5-HT-moduline is a novel endogenous
      peptide regulating the serotonergic activity via a direct action at presynaptic 5
      HT receptor. It may play an important role in the physiological mechanisms
      involving the serotonergic system, particularly in mechanisms corresponding to
      the elaboration of an appropriate response of the central nervous system to a
      given stimulus.

PMID- 8863820
TI  - Blockade of DNA synthesis induced by platelet-derived growth factor by tranilast,
      an inhibitor of calcium entry, in vascular smooth muscle cells.
AB  - The present study was conducted to establish a pharmacological method of
      controlling growth of vascular smooth muscle cells (VSMC) by blocking calcium
      entry. In cultured rat VSMC, 1 nM platelet-derived growth factor (PDGF) induced a
      biphasic elevation of cytoplasmic free calcium concentration, ([Ca2+]c). The
      second sustained phase of [Ca2+]c was dependent on extracellular calcium. At
      lower concentrations, PDGF induced oscillatory changes in [Ca2+]c, and reduction
      of extracellular calcium attenuated the oscillation. An antiallergic compound,
      tranilast, abolished the sustained phase of [Ca2+]c induced by 1 nM PDGF.
      Tranilast also inhibited the oscillatory changes in [Ca2+]c induced by 200 pM
      PDGF. In addition, PDGF-induced calcium influx in the late G1 phase, as assessed
      by measuring the initial uptake of 45Ca, was inhibited by tranilast in a
      concentration-dependent manner. Tranilast also inhibited PDGF-augmented DNA
      synthesis; the ID50 for the inhibition of DNA synthesis was nearly identical to
      that for calcium influx. Although tranilast blocked PDGF-induced calcium entry,
      it did not affect PDGF-mediated autophosphorylation of the PDGF receptor,
      activation of phosphatidylinositol 3-kinase, activation of Ras or mitogen
      activated protein kinase. Similarly, PDGF-induced elevation of diacylglycerol was
      not affected by tranilast. These results suggest that the antiallergic drug
      tranilast inhibits PDGF-induced DNA synthesis by blocking PDGF-mediated calcium
      entry. Tranilast may be of use in controlling PDGF-induced DNA synthesis in VSMC.

PMID- 8863821
TI  - Ligand-binding characteristics and related structural features of the expressed
      goldfish kainate receptors: identification of a conserved disulfide bond and
      three residues important for ligand binding.
AB  - Low-molecular-weight kainate receptors from nonmammalian vertebrate brain belong
      structurally to the ionotropic glutamate receptor superfamily. In this study, two
      previously cloned goldfish kainate receptor subunits (GFKAR alpha and GFKAR beta)
      were transiently expressed in human embryonic kidney 293 cells, and their ligand
      binding properties and some associated structural features were characterized,
      resulting in the following findings. 1) Both subunits form homomeric receptors
      with high affinity for [3H]kainate (KD = 16 and 31 nM, respectively) and L
      glutamate (KD = 2 and 40 microM, respectively). 2) A deletion mutant lacking the
      originally proposed second-transmembrane domain was efficiently expressed and
      retains the overall ligand-binding properties of wild-type GFKAR alpha, strongly
      indicating that this region is not a transmembrane domain. 3) Mutations of Q12,
      A53, and Y54 of GFKAR beta indicate that these three residues are important for
      ligand binding (particularly L-glutamate), which is consistent with the sequence
      homology to bacterial periplasmic binding proteins. 4) Mutation of the three
      extracellular cysteine residues of GFKAR beta indicated that the two conserved
      cysteine residues (C305 and C385), located between two transmembrane segments,
      form a solvent-accessible disulfide bond. Analysis of [3H]kainate binding to wild
      type and cysteine mutations of GFKAR beta indicate that in the absence of the
      disulfide bond, the affinity for kainate is increased 3-fold. These data lend
      further evidence in support of a model of glutamate receptor topology with three
      transmembrane segments and reveal several general structural features of the
      extracellular ligand-binding domain of the kainate receptors. These results are
      consistent with the notion that the ligand-binding domain has close structural
      similarities to bacterial periplasmic binding proteins.

PMID- 8863822
TI  - Baculovirus-mediated expression and characterization of rat CYP2A3 and human
      CYP2a6: role in metabolic activation of nasal toxicants.
AB  - Cytochrome P450 2A3 (CYP2A3) was previously identified in rat lung by cDNA
      cloning and recently found to be expressed at a high level in the olfactory
      mucosa. In the current study, CYP2A3 was expressed in insect cells lacking
      endogenous cytochrome P450 (P450) activity, and the substrate specificity of the
      recombinant cytochrome was characterized and compared with that of CYP2A6, a
      human ortholog of rat CYP2A3, which has been detected in human olfactory mucosa
      as well as in liver. The CYP2A3 and CYP2A6 cDNAs were cloned into baculovirus,
      and recombinant viruses were used to produce active enzymes in Spodoptera
      frugiperta (SF9) cells. The metabolic activities of S. frugiperta cell microsomal
      fractions containing CYP2A3 or CYP2A6 were studied in a reconstituted system with
      purified rabbit NADPH-P450 reductase. CYP2A3 was found to be active toward
      testosterone, producing 15 alpha-hydroxytestosterone and several other
      metabolites, but it had only low activity toward coumarin. On the other hand,
      CYP2A6 was active toward coumarin but not toward testosterone. However, both
      enzymes were active in the metabolic activation of hexamethylphosphoramide, a
      nasal procarcinogen, and 2,6-dichlorobenzonitrile (DCBN), a herbicide known to
      cause tissue-specific toxicity in the olfactory mucosa of rodents at very low
      doses. In addition, both enzymes were active toward 4-nitrophenol, a preferred
      substrate for CYP2E1. Consistent with CYP2A3 being a major catalyst in microsomal
      metabolism of DCBN, the activities of both CYP2A3 and rat olfactory microsomes in
      DCBN metabolism were inhibited strongly by metyrapone and methoxsalen (ID50 < 1
      microM, with DCBN at 30 microM), but only marginally by 4-methylpyrazole, an
      inhibitor of CYP2E1. In contrast, the activity of CYP2A6 was only weakly
      inhibited by metyrapone or methoxsalen (ID50 > 50 microM). Thus, rat CYP2A3 and
      human CYP2A6 have differences in substrate specificity as well as tissue
      distributor. These findings should be taken into account when assessing the risk
      of exposure to potential nasal toxicants in humans.

PMID- 8863823
TI  - Covalent modification of transmembrane span III of the A1 adenosine receptor with
      an antagonist photoaffinity probe.
AB  - Structure-based design of subtype-selective ligands for the A1 adenosine receptor
      will require a reliable model of the ligand-binding pocket. It should be possible
      to develop a reliable model based on the results of affinity labeling experiments
      that provide atomic coordinates for the ligand in relation to predicted receptor
      helices. A high affinity, A1-selective xanthine antagonist photoaffinity probe,
      125l-3-(4-azidophenethyl)-1-propyl-B-cyclopentylxanthine, was used to covalently
      modify the A1 receptor. Chemical or enzymatic fragmentation experiments were
      performed to localize the region or regions of incorporation within the receptor.
      The fragmentation profiles for radiolabeled A1 receptor obtained with
      endoproteinase Glu-C, endoproteinase Lys-C, cyanogen bromide, and hydroxylamine
      were consistent with the interpretation that the covalent linkage was within the
      first four predicted transmembrane regions. This interpretation was confirmed by
      the demonstration that the radioactive endoproteinase Glu-C fragment derived from
      an A1 receptor that contains an amino-terminal FLAG epitope was recognized by an
      anti-FLAG monoclonal antibody. Sequential digestion with endoproteinase Glu
      C/endoproteinase Lys-C limited the possible labeling to the first three predicted
      transmembrane spans, and endoproteinase Glu-C/trypsin digestion refined this
      prediction to include only transmembrane spans III and IV. Taken together, our
      findings suggest that the adenosine antagonist 125l-3-(4-azidophenethyl)-1-propyl
      8-cyclopentyl-xanthine covalently modifies transmembrane III of the A1 receptor
      because this was the only receptor region common to all radiolabeled fragments.

PMID- 8863824
TI  - Identification, molecular cloning, and distribution of a short variant of the 5
      hydroxytryptamine2C receptor produced by alternative splicing.
AB  - The actions of the neurotransmitter 5-hydroxytryptamine (5-HT) (serotonin) are
      mediated by multiple receptor subtypes. One of the prominent serotonin receptors
      in the brain is the 5-HT2C receptor (5-HT2C-R). We report the occurrence of a
      second 5-HT2C-R transcript, first identified using S1 nuclease protection of
      total RNA isolated from the choroid plexus. Analyses of the distribution of these
      two RNAs revealed that the short form is expressed in the same structures as the
      5-HT2C-R mRNA, including choroid plexus, striatum, hippocampus, hypothalamus,
      olfactory tubercles, and spinal cord. Cloning and sequence analyses revealed a
      second cDNA with a 95-nt deletion in the region coding for the putative second
      intracellular loop and the fourth transmembrane domain of the 5-HT2C-R. This
      deletion leads to a frameshift in the coding sequence and the introduction of a
      premature stop codon. The predicted truncated protein (5-HT2C-tr) contains 172
      amino acids, with 153 residues at the amino terminus, identical to the 5-HT2C-R,
      and 19 carboxyl-terminal amino acids that are unique. Although antibodies
      specific to the 5-HT2C-tr protein showed that the truncated form is expressed in
      a transfected fibroblast cell model system, there was no serotonergic ligand
      binding activity or phosphoinositide hydrolysis. Analyses of the 5-HT2C-R gene
      revealed that the two transcripts arise from a single gene by differential
      splicing using alternative donor sites and a common 3'-splice acceptor.
      Polymerase chain reaction amplification of mouse and human brain cDNAs
      demonstrated the occurrence of the same splicing patterns in these species.
      Although this study demonstrates tissue-specific expression of two 5-HT2C mRNA
      splice variants in rat, mouse, and human, the significance of the truncated form
      in these three species remains to be established.

PMID- 8863825
TI  - Inhibition of expression of the multidrug resistance-associated P-glycoprotein of
      by phosphorothioate and 5' cholesterol-conjugated phosphorothioate antisense
      oligonucleotides.
AB  - Multiple drug resistance (MDR) as a result of overexpression of the P
      glycoprotein drug transporter, a product of the MDR1 gene, is a significant
      problem in cancer therapeutics. We demonstrate that phosphorothioate antisense
      oligonucleotides can reduce levels of MDR1 message, inhibit expression of P-glyco
      protein, and affect drug uptake in MDR mouse 3T3 fibroblasts. An obligonucleotide
      (5995) directed against a sequence overlapping the AUG start codon was effective
      in reduction MDR1 transcript and protein levels when used at submicromolar
      concentrations in conjunction with cationic liposomes, whereas a scrambled
      control oligonucleotide (10221) was ineffective. Substantial and specific
      antisense effects could also be attained with a 5' cholesterol conjugate of the
      5995 sequence. In this case, use of cationic liposomes was unnecessary. The 5'
      cholesterol 5995, but the not 5' cholesterol 10221, reduced MDR1 message and P
      glycoprotein levels by 50-60% when used at low micromolar concentrations. In
      parallel, treatment with 5' cholesterol 5995 also enhanced cellular accumulation
      of rhodamine 123, a well-known substrate of the P-glycoprotein transporter. The
      effectiveness of the cholesterol-conjugated 5995 may be due to its rapid and
      extensive cell uptake, as indicated in flow cytometry and confocal microscopy
      studies. These observations suggest that cholesterol-conjugated anti-sense
      oligonucleotides may offer a novel approach to inhibition of P-glycoprotein
      mediated MDR and to the modulation of other tumor cell genes whose overexpression
      contributes to the neoplastic state or to resistance to therapy.

PMID- 8863826
TI  - Vasopressin V2 receptor mutants that cause X-linked nephrogenic diabetes
      insipidus: analysis of expression, processing, and function.
AB  - We investigated the biochemical and functional properties of five vasopressin V2
      receptor mutants (L44F, L44P, W164S, S167L, and S167T) that were recently
      described in families with a history of X-linked nephrogenic diabetes insipidus.
      COS.M6 cells transfected with cDNA encoding these mutants acquired < 4% specific
      [3H]arginine vasopressin (AVP) binding sites on the cell surface in comparison
      with cells transfected with cDNA coding for the wild-type receptor. Membrane
      preparations from COS.M6 cells or human embryonic kidney 293 cells expressing
      these mutants did not respond with an increase in adenylyl cyclase activity in
      response to AVP, which is in contrast to membranes from cells expressing the wild
      type. By analyzing fusion proteins of the V2 receptor and Escherichia coli
      alkaline phosphatase attached to the carboxyl terminus of the receptor moiety, we
      found that the mutants L44P, W164S, S167L, and S167T lacked complex glycosylation
      and were expressed at low levels. The data suggest that the mutants L44P, W164S,
      S167T, and S167L are misfolded and therefore retained within the endoplasmic
      reticulum and degraded. In contrast, the fusion proteins carrying the mutant L44F
      and the in vitro mutant S167A were expressed in their mature form at wild-type
      levels; however, only the mutant S167A was functionally active. Site-directed
      mutagenesis of S167 revealed that elimination of the endogenous hydroxyl group
      (S167A) yielded a protein with properties identical to those of the wild-type
      receptor, whereas both the introduction of a methyl group (S167T) and the
      replacement of the hydroxyl group by an isopropyl group (S167L) profoundly
      disturbed receptor processing. The data show that minute changes at codon 167
      nearly abolish expression of a mature protein, thus defining structural
      requirements of this codon.

PMID- 8863827
TI  - Pharmacological characterization of the rat A2a adenosine receptor functionally
      coupled to the yeast pheromone response pathway.
AB  - The rat A2a adenosine receptor, a G protein-coupled receptor, was functionally
      expressed in the yeast Saccharomyces cerevisiae. High affinity binding sites for
      A2a adenosine agonists were detected in yeast membranes containing the endogenous
      Grx protein Gpa1. Agonist saturation binding isotherms using [3H]5'-N
      ethylcarboxamidoadenosine indicated that the A2a adenosine receptor expressed in
      yeast cell membranes displays pharmacological properties equivalent to those
      observed when the receptor is expressed in human embryonic kidney 293 cell
      membranes. The rank order of potency of various agonists in [3H]5'-N
      ethylcarboxamidoadenosine competition binding assays performed with yeast cell
      membranes was comparable to that seen for the receptor expressed in mammalian
      cell membranes. Adenosine agonist-dependent growth response of yeast strains
      expressing the A2a adenosine receptor was elicited via activation of the yeast
      pheromone-response pathway. Induction of a pheromone-responsive FUS1-HIS3
      reporter gene in far1 his3 cells permits cell growth in medium lacking histidine.
      The sensitivity of the bioassay was increased by deletion of the STE2 gene, which
      encodes the yeast alpha-mating pheromone receptor. The growth response was dose
      dependent, and agonists of varying affinities displayed a rank order of potency
      comparable to that observed in competition binding assays. Agonist-activated
      growth assays performed in liquid culture gave ED50 values for various adenosine
      agonists consistent with reported Kd alpha values. Yeast strains expressing a
      single receptor/G protein complex will be useful as a model system for the study
      of receptor/G protein interactions in vivo.

PMID- 8863828
TI  - Aza-bioisosteres of 9, 10-anthracenedione: a modulation of DNA sequence
      specificity.
AB  - The sequence specificity of DNA-binding by monoaza- and diaza-anthracenedione
      analogues of mitoxantrone (MX) has been investigated by DNase 1 footprinting and
      spectroscopic techniques. More than 100 sites cut by the enzyme were sequenced on
      three pBR 322 and simian virus 40 DNA restriction fragments. Different inhibition
      and stimulation effects were observed as a function of the structural properties
      of each drug. A gradual change was found from MX to monoaza derivatives and from
      these to diaza derivatives, corresponding to a broader distribution of drug
      inhibited regions. In addition to almost all sites found with MX (38 of 44), 29
      new inhibition sites were observed using the diaza compound BBR 2894. The
      sequence analyses in terms of base doublets or triplets confirm the preference of
      MX for alternating pyrimidine-purine sites, the most significant triplet
      sequences being (5' to 3') CTA, GCA, TAC, ACT, CAC and TTA. In addition to MX
      sites, BBR 2894 seemed to bind efficiently to pyrimidine-pyrimidine-pyrimidine or
      purine-pyrimidine-pyrimidine triplets containing CT or TC motifs. Differential
      cleavage plots essentially confirmed the above results. Spectrophotometric and
      chiroptical studies showed a decreased DNA-binding affinity and a modified
      geometry of intercalation when nitrogen replaces carbon in the anthraquinone
      ring. These results can be useful for understanding the substantially different
      biological responses exhibited by aza-substituted anthracenedlones when compared
      with their non-substituted, pharmacologically relevant congeners.

PMID- 8863829
TI  - Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase:
      inhibition of the core catalytic domain of human immunodeficiency virus
      integrase.
AB  - Integration of a cDNA copy of the human immunodeficiency virus (HIV) genome is
      mediated by an HIV-1-encoded enzyme, integrase (IN), and is required for
      productive infection of CD4+ lymphocytes. It had been shown that 3,5
      dicaffeoylquinic acid and two analogues were potent and selective inhibitors of
      HIV-1 IN in vitro. To determine whether the inhibition of IN by dicaffeoylquinic
      acids was limited to the 3,5 substitution, 3,4-, 4,5-, and 1,5-dicaffeoylquinic
      acids were tested for inhibition of HIV-1 replication in tissue culture and
      inhibition of HIV-1 IN in vitro. All of the dicaffeoylquinic acids were found to
      inhibit HIV-1 replication at concentrations ranging from 1 to 6 microM in T cell
      lines, whereas their toxic concentrations in the same cell lines were > 120
      microM. In addition, the compounds inhibited HIV-1 IN in vitro at submicromolar
      concentrations. Molecular modeling of these ligands with the core catalytic
      domain of IN indicated an energetically favorable reaction, with the most potent
      inhibitors filling a groove within the predicted catalytic site of IN. The
      calculated change in internal free energy of the ligand/IN complex correlated
      with the ability of the compounds to inhibit HIV-1 IN in vitro. These results
      indicate that the dicaffeoylquinic acids as a class are potent and selective
      inhibitors of HIV-1 IN and form important lead compounds for HIV drug discovery.

PMID- 8863830
TI  - Glucocorticoid receptor-independent transcriptional induction of cytochrome P450
      3A1 by metyrapone and its potentiation by glucocorticoid.
AB  - Metyrapone administration to 21- and 90-day-old male rats causes a
      transcriptional induction of the hepatic glucocorticoid-inducible CYP3A1 gene
      within an hour as determined by nuclear run-on experiments. Analyses performed 24
      hr after metyrapone administration in both ages of rat demonstrate that the
      transcriptional induction of CYP3A1 gene expression is followed by significant
      increases in CYP3A1 mRNA, CYP3A-immunoreactive microsomal protein and total
      microsomal cytochrome P450 (CYP). In 21-day-old rats, there is a significant
      increase in microsomal CYP3A dependent steroid 6 beta-hydroxylase activity but
      not in 90-day-old rats, possibly because of a slower clearance of this drug,
      which inhibits CYP activities. In hepatocytes cultured in serum- and
      glucocorticoid hormone-free medium, metyrapone alone induces CYP3A1 mRNA
      expression, which demonstrates that metyrapone transcriptionally induces hepatic
      CYP3A1 by a direct interaction with the liver. Metyrapone does not compete with
      the binding of the synthetic glucocorticoid and potent transcriptional CYP3A1
      inducer dexamethasone to the glucocorticoid receptor (GR) in soluble fractions
      from liver. This suggests that metyrapone is not a ligand for the GR and induces
      CYP3A1 by a mechanism independent of the GR. Addition of glucocorticoid to
      cultured hepatocytes at levels that induce GR-dependent genes potentiate CYP3A1
      mRNA induction by metyrapone without inducing CYP3A1 mRNA alone. A GR-dependent
      mechanism may therefore mediate the potentiation of CYP3A1 transcriptional
      induction by metyrapone. The CYP3A1 transcriptional inducer and glucocorticoid
      antagonist pregnenolone 16 alpha-carbonitrile at 100 microM blocks dexamethasone
      binding to the GR in 21-day-old rat liver soluble fractions but is less effective
      in 90-day-old rat liver soluble fractions in contrast with 10 microM
      glucocorticoid antagonist RU486, which is equally effective at blocking
      dexamethasone binding to the GR. The inability of pregnenolone 16 alpha
      carbonitrile to fully compete with dexamethasone for cytosolic binding in adult
      animals suggests that there may exist variant receptors with different affinities
      for dexamethasone and pregnenolone 16 alpha-carbonitrile and may explain the
      mechanism by which low concentrations of dexamethasone potentiate the
      transcriptional induction of CYP3A1 mediated by high concentrations of
      pregnenolone 16 alpha-carbonitrile [J. Biol, Chem. 270:28917-28923 (1995)].
      Examination of membrane-bound dexamethasone binding activity, with which other
      steroidal and nonsteroidal CYP3A inducers have been shown to compete, indicates
      that binding activity is detectable in 90- but not 21-day-old rat liver
      microsomes. The absence of membrane-bound glucocorticoid binding site activity
      and the presence of a functional CYP3A1 transcriptional response in 21-day-old
      rats suggest that membrane-bound glucocorticoid binding site activity is not
      involved in the transcriptional activation of CYP3A1 expression. These data
      suggest that both glucocorticoids and nonsteroidal compounds may trigger the
      transcriptional induction of CYP3A1 by a GR-independent mechanism that may be
      potentiated by a GR-dependent mechanism.

PMID- 8863831
TI  - Inhibition by toxin B of inositol phosphate formation induced by G protein
      coupled and tyrosine kinase receptors in N1E-115 neuroblastoma cells: involvement
      of Rho proteins.
AB  - G protein-coupled receptors activate phospholipase C (PLC)-beta isoforms by the
      alpha or beta gamma subunits of G proteins, whereas growth-factor receptors
      activate PLC-gamma isoforms by phosphorylating tyrosine residues of the enzyme.
      As a common substrate for PLC enzymes, phosphatidylinositol 4,5-bisphosphate
      [Ptdins(4,5)P2] may play a pivotal role in the regulation of cellular PLC
      activity. Because small-molecular-weight G proteins have been implicated in the
      synthesis of Ptdins(4,5)P2, we studied the effect of Clostridium difficile toxin
      B, which glucosylates and thereby inactivates small G proteins of the Rho family,
      on receptor-stimulated PLC activity. We report here that in N1E-115 neuroblastoma
      cells, stimulation of inositol phosphate formation by the G protein-coupled
      receptor agonists bradykinin and lysophosphatidic acid and by the tyrosine kinase
      receptor agonist platelet-derived growth factor is largely attenuated by toxin B
      treatment. Furthermore, inositol phosphate production stimulated by the stable
      GTP analog guanosine 5'-O-(3-thio)-triphosphate in permeabilized N1E-115 cells
      was inhibited by C3 exoenzyme, which specifically inactivates Rho proteins. The
      inhibition by toxin B was apparently not caused by its effect on the
      cytoskeleton. In addition, the level of platelet-derived growth factor receptors,
      which was studied with immunoblotting, was unaffected by toxin B. Using exogenous
      Ptdlns(4,5)P2 as PLC substrate, it was found that the intrinsic enzymatic
      activity of PLC activated either by Ca2+ or by guanosine 5'-O-(3
      thio)triphosphate was not altered by toxin B. However, toxin B decreased
      strongly, by up to 80%, the cellular level of Ptdins(4,5)P2 in a concentration
      dependent manner, without changing those of phosphatidylinositol and
      phosphatidylinositol 4-phosphate. These results, together with the recent finding
      that Rho family proteins can regulate phosphatidylinositol 4-phosphate 5-kinase
      activity, demonstrate that Rho proteins are presumably important regulators of
      Ptdins(4,5)P2 synthesis and, thereby, play an integral role in the regulation of
      cellular signaling by PLC enzymes.

PMID- 8863832
TI  - Opioid mu, delta, and kappa receptor-induced activation of phospholipase C-beta 3
      and inhibition of adenylyl cyclase is mediated by Gi2 and G(o) in smooth muscle.
AB  - In neurons and transformed cell lines, opioid receptors are coupled to various
      signaling mechanisms involved in Ca2+ mobilization, including inhibition or
      activation of Ca2+ channels and phospholipase C-beta (PLC-beta), the enzyme
      responsible for generation of the Ca2+ mobilizing messenger inositol-1,4,5
      trisphosphate [Ins(1,4,5)P3]. In the current study, we used selective PLC-beta
      and G protein antibodies to identify the PLC-beta isozyme activated by opioid
      receptors in intestinal smooth muscle and the G proteins to which the PLC-beta
      isozyme and adenylyl cyclase are coupled. [D-Pen2,D-Pen5]Enkephalin, a delta
      receptor agonist, stimulated Ins(1,4,5)P3 formation, Ca2+ release, and
      contraction; inhibited forskolin-stimulated cAMP formation in dispersed muscle
      cells; and stimulated phosphoinositide hydrolysis in plasma membranes; all of the
      effects were blocked by pertussis toxin. [D-Pen2,D-Pen5]Enkephalin-stimulated
      Ins(1,4,5)P3 formation, Ca2+ release, and contraction in permeabilized muscle
      cells and phosphoinositide hydrolysis in plasma membranes were selectively
      blocked by G beta antibody and PLC-beta 3 antibody; contractions stimulated by [D
      Ala2,N-MePhe4,Gly-ol5]enkephalin, a mu receptor agonist, and U-69,593, a kappa
      receptor agonist, were also blocked by G beta and PLC-beta 3 antibodies.
      Inhibition of forskolin-stimulated cAMP formation by delta, mu, and kappa
      receptor agonists was partially blocked by G alpha i2 and G alpha o antibodies
      and additively blocked by a combination of the antibodies. The delta, mu, and
      kappa receptor agonists stimulated the binding of guanosine-5'-O-(3
      thio)triphosphate to the alpha subunits of Gi2 and G(o) but not to the alpha
      subunits of other G proteins. We conclude that opioid mu, delta, and kappa
      receptors are selectively coupled to Gi2 and G(o) in intestinal smooth muscle.
      The beta gamma subunits of both G proteins activate PLC-beta 3, thereby
      stimulating Ins(1,4,5)P3-dependent Ca2+ release and smooth muscle contraction,
      whereas the alpha subunits inhibit adenylyl cyclase activity.

PMID- 8863833
TI  - Acemannan, a beta-(1,4)-acetylated mannan, induces nitric oxide production in
      macrophage cell line RAW 264.7.
AB  - Acemannan is a polydispersed beta-(1,4)-linked acetylated mannan with antiviral
      properties. It is an immunomodulator, and studies in our laboratory have shown
      that it causes activation of macrophages. Inducible NO synthase is generally
      expressed after transcriptional induction and is known to mediate some of the
      cytotoxic action of activated macrophages. Acemannan, in the presence of
      interferon-gamma, greatly increased the synthesis of NO in RAW 264.7 cells. This
      increase was preceded by increased expression of mRNA for the inducible form of
      macrophage NO synthase. Preincubation with pyrrolidine dithiocarbamate inhibited
      the induction, indicating the involvement of nuclear factor-kappa B. These
      results suggest that acemannan causes the activation of macrophages by increasing
      the level of NO synthase at the level of transcription.

PMID- 8863834
TI  - Carboxyl-terminal mutations of Gq alpha and Gs alpha that alter the fidelity of
      receptor activation.
AB  - The carboxyl terminus of the G protein alpha subunit is a key determinant of the
      fidelity of receptor activation. We have previously shown that the Gq alpha
      subunit (alpha q) can be made to respond to alpha i-coupled receptors by
      replacing its carboxyl terminus with the corresponding alpha i2, alpha o, alpha z
      residues. We now extend these findings in three ways: 1) carboxyl-terminal
      mutations of alpha q/alpha i chimeras show that the critical amino acids are in
      the -3 and -4 positions, 2) exchange of carboxyl termini between alpha q and
      alpha z allows activation by receptors appropriate to the carboxyl-terminal
      residues, and 3) we identify receptors that either do or do not activate the
      expected carboxyl-terminal chimeras (alpha q/alpha i, alpha q/alpha s, alpha
      s/alpha q). Replacement of the five carboxyl-terminal amino acids of alpha q with
      the alpha s sequence permitted an alpha s-coupled receptor (the V2 vasopressin
      receptor but not the beta 2-adrenergic receptor) to stimulate phospholipase C.
      Replacement of the five carboxyl-terminal amino acids of alpha z with residues of
      alpha q permitted certain alpha q-coupled receptors (bombesin and V1a vasopressin
      receptors but not the oxytocin receptor) to stimulate adenylyl cyclase. Thus, the
      relative importance of the G alpha carboxyl terminus in permitting coupling to a
      new receptor depends on the receptor with which it is paired. These studies
      refine our understanding and provide new tools with which to study the fidelity
      of receptor/G alpha activation.

PMID- 8863835
TI  - Mapping the functional domains of human recombinant phosphodiesterase 4A:
      structural requirements for catalytic activity and rolipram binding.
AB  - To identify functional domains of the 886-amino acid human recombinant cAMP
      specific phosphodiesterase (PDE) subtype A (rhPDE4A), we engineered the
      expression of seven mutant proteins containing both NH2- and COOH-terminal
      truncations. The level of rhPDE4A protein expression in yeast was monitored by
      immunoblotting using enzyme-specific antisera. Biochemical profiles of the mutant
      proteins were compared with those of the full-length protein or a fully active
      truncated form of the enzyme (rhPDE4A Met265-886), lacking the first 264 amino
      acids. The smallest catalytically active fragment generated was Met332-722, which
      at 45 kDa is less than half the mass of the full-length enzyme (approximately 110
      kDa) but spans the most highly conserved region of the PDE superfamily. Two
      prototypical PDE4 inhibitors, rolipram and RP 73401, inhibited cAMP hydrolyzing
      activity of all truncated forms of the enzyme, with IC50 values of 70-2000 nM and
      0.2-0.6 nM, respectively. [3H](R)-Rolipram bound to two sites on Met265-886, a
      high affinity site (Kd1 = 0.7 +/- 0.3 nM) and a low affinity site (Kd2 = 34 +/-
      10 nM). Interestingly, [3H](R)-rolipram failed to bind to Met332-886 with high
      affinity, indicating that high affinity binding is not required for inhibition of
      enzyme activity. Low affinity rolipram binding was still present in Met332-886
      (Kd = 101 +/- 7 nM). In contrast to [3H](R)-rolipram, [3H]RP 73401 bound to a
      single class of high affinity sites on Met265-886 (Kd = 0.4 +/- 0.1 nM). Further
      truncation of the enzyme to Met332-886 had no effect on [3H]RP 73401 binding (Kd
      = 0.2 +/- 0.03 nM). We conclude that the catalytic center of rhPDE4A lies between
      amino acids 332 and 722. Furthermore, amino acids 265-332 may form a high
      affinity binding site for rolipram that is outside of the catalytic domain. As a
      more likely alternative, these amino acids may not form a distinct binding site
      but instead may be required for the recombinant enzyme to assume a conformation
      that binds rolipram at the catalytic domain with a high affinity.

PMID- 8863836
TI  - DNA-damaging agents induce both p53-dependent and p53-independent apoptosis in
      immature thymocytes.
AB  - Apoptosis in the immature thymus can be induced by both p53-dependent and 
      independent pathways, the former being activated by exposure to DNA-damaging
      agents and the latter being induced by glucocorticoids [Nature (Lond.) 362:847
      849; Nature (Lond.) 362:849-852 (1993)]. We report that the DNA-damaging agents
      etoposide and gamma-radiation induced similar levels of apoptosis in both
      proliferatively enriched and quiescent immature rat thymocytes, as assessed by
      flow cytometry and the formation of both kilobase-pair and 180-bp integer
      fragments of DNA. However, a marked stabilization of p53 occurred exclusively in
      the proliferatively enriched population, which was also enriched for immature CD4
      CD8- and mature CD4+ CD8-/CD4- CD8+ cells. In contrast, DNA damage-induced
      apoptosis in quiescent mature peripheral T cells was associated with an
      accumulation of p53. Our studies suggest that stabilization of p53 in thymocytes
      in response to DNA damage may be developmentally regulated. In immature
      thymocytes obtained from p53-null mice, DNA-damaging agents induced apoptosis at
      significantly lower levels and at later times than that seen in cells from p53
      wild-type animals. These data support the hypothesis that DNA-damaging agents
      induce apoptosis primarily via a p53-dependent pathway in immature thymocytes as
      previously reported. We report here that DNA damage can also induce apoptosis by
      a p53-independent pathway in a particular subpopulation of immature thymocytes.

PMID- 8863837
TI  - Functional coupling of rat group II metabotropic glutamate receptors to an omega
      conotoxin GVIA-sensitive calcium channel in human embryonic kidney 293 cells.
AB  - Metabotropic glutamate receptors are G protein-coupled receptors that perform a
      variety of modulatory roles in the central and peripheral nervous systems. The
      development of receptor subtype-specific agonists/antagonists has lagged far
      behind the isolation and characterization of receptor cDNAs. Further more, the
      coupling of specific metabotropic receptors to the various neuronal-specific
      effector molecules, such as voltage gated Ca2+ channels, has not been well
      studied. It was recently demonstrated that a rat group II metabotropic receptor
      (rm-GluR2) is capable of coupling to endogenous N-type Ca2+ channels when
      heterologously expressed in adult rat sympathetic ganglia neurons. To eventually
      understand the molecular aspects of metabotropic receptor modulation of the N
      type Ca2+ channel, we have transiently expressed both group II receptors in a
      human embryonic kidney 293 cell line (G1A1) that stably expresses the human alpha
      1B-1, alpha 2b, and beta 1-3 Ca2+ channel subunits. rmGluR2 and rmGluR3 modulate
      the omega-conotoxin GVIA-sensitive Ba2+ currents in G1A1 cells using a voltage
      dependent mechanism via an endogenous pertussis toxin-sensitive G protein. Cell
      attached "macropatch" recordings demonstrate that modulation by rmGluR2 and
      rmGluR3 is membrane delimited. This is the first report of Ca2+ channel
      modulation mediated by rmGluR3. In addition, an extensive pharmacological
      comparison between rmGluR2 and rmGluR3 reveals that these group II receptors
      interact with agonists and antagonists in unique ways.

PMID- 8863838
TI  - Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16,
      and chimeric G alpha q/i proteins: characterization of new antagonists.
AB  - Together with the calcium-sensing receptor, the metabotropic glutamate receptors
      (mGluRs) share no sequence homology with the other G protein-coupled receptors
      (GPCRs) and therefore constitute a new family of receptors. Recently, it was
      reported that G alpha 15 and G alpha 16 subunits allow many GPCRs to activate
      phospholipase C (PLC). Furthermore, the exchange of a few carboxyl-terminal
      residues of G alpha q by those of G alpha 12 or G alpha o allows the resulting
      chimeric G alpha subunits (G alpha ql and G alpha qol respectively) to couple Gi
      coupled receptors to PLC. We report that mGluR2 and mGluR4, two receptors
      negatively coupled to adenylyl cyclase, activate PLC when coexpressed with G
      alpha 15, G alpha ql or G alpha qo. This indicates that the carboxyl-terminal end
      of the G alpha subunit also plays an important role in the specific interaction
      between mGluRs and the G proteins. In addition, the measurement of PLC activation
      by Gi-coupled mGluRs coexpressed with these G alpha subunits constitutes an easy
      functional assay for the pharmacological characterization of these receptors. The
      rank order of potency of antagonists was found to be (2S,3S,4S)-2-methyl-2
      (carboxycyclopropyl)glycine approximately (R,S)- alpha-methyl-4
      phosphonophenylglycine > (R,S)-alpha-methyl-4-sulfonophenylglycine > (R,S)-alpha
      methyl-4-tetrazolylphenylglycine = (S)-2-amino-2-methyl-4-phosphonobutyrate for
      mGluR2 and to be (R,S)-alpha-methyl-4-phosphonophenylglycine > or = (S)-2-amino-2
      methyl-4-phosphonobutyrate > > (R,S)-alpha-methyl-4-sulfonophenylglycine [(R,S)
      alpha-methyl-4-tetrazolylphenylglycine and (2S,3S,4S)-2-methyl-2
      (carboxycyclopropyl)glycine being inactive at 1 mM] for mGluR4. Using this
      functional assay, (R,S)-alpha-methyl-4-phosphonophenylglycine was found to have a
      similar KB value for mGluR2 and mGluR4.

PMID- 8863839
TI  - Endogenous subunits can cause ambiguities in the pharmacology of exogenous gamma
      aminobutyric acidA receptors expressed in human embryonic kidney 293 cells.
AB  - The physiological and pharmacological properties of GABAA receptors have been
      studied extensively after the expression of subunits in non-neural cells. Many of
      these studies have used the human embryonic kidney cell line HEK 293. We examined
      the properties of subunits that result in the expression of low levels of
      functional receptors and found that the properties of the gamma-aminobutyric acid
      (GABA)-elicited responses in transfected HEK 293 cells differ from expectations
      based on previous work and are consistent with the idea that the expressed
      receptors do not necessarily contain the expected subunits. In particular,
      expression of a mutated beta 2 subunit [beta 2(Y205S)] in combination with alpha
      1 and gamma 2L results in cells that have large responses to pentobarbital (as
      expected) but also show appreciable responses to GABA (contrary to expectation).
      Furthermore, transfection of HEK 293 cells with alpha 1 plus gamma 2L subunits
      results in responses to GABA that are potentiated by the drug loreclezole,
      suggesting that a subunit resembling the beta 2 or beta 3 subunit had assembled
      with the alpha 1 gamma 2L subunits. In addition, some nontransfected HEK 293
      cells respond to applications of GABA, and transfection of cells with alpha 1,
      beta 1, or gamma 2L subunits alone can result in the expression of GABA-elicited
      currents. In comparison, when QT6 quail fibroblasts are used as the expression
      system, no responses were seen in untransfected cells or in cells transfected
      with alpha 1, beta 1, or gamma 2L subunits alone or alpha 1 gamma 2L subunits.
      Furthermore, no response to GABA was seen in QT6 cells transfected with alpha 1
      beta 2(Y205S) gamma 2L subunits, although cells gave strong responses to
      pentobarbital. These observations indicate that caution must be taken in
      interpreting the results of studies of the properties of GABAA receptors
      expressed in HEK 293 cells if the exogenous subunits result in the expression of
      low levels of functional GABAA receptors.

PMID- 8863840
TI  - Block of high-threshold calcium channels by the synthetic polyamines sFTX-3.3 and
      FTX-3.3.
AB  - A polyamine component of Agelenopsis aperta spider venom designated FTX is
      reported to be a selective antagonist of P-type calcium channels in the mammalian
      brain. Consequently, this component has frequently been used as a pharmacological
      tool to determine the presence, distribution, and function of P-type channels in
      physiological systems. We describe antagonism of calcium channels by the
      synthesized polyamine FTX-3.3, which has the proposed structure of natural FTX.
      We also examined a corresponding polyamine amide, sFTX-3.3. These polyamines are
      critically evaluated for antagonism of three high-threshold calcium channel
      subtypes in rat neurons through the use of the whole-cell patch-clamp technique.
      FTX-3.3 (IC50 = approximately 0.13 mM) is approximately twice as potent as sFTX
      3.3 (IC50 = approximately 0.24 mM) against P-type channels and approximately 3
      fold more potent against N-type channels (FTX-3.3, IC50 = approximately 0.24 mM;
      sFTX-3.3, IC50 = approximately 0.70 mM). Both polyamines also block L-type
      calcium channels with similar potencies. sFTX-3.3 (1 mM) and FTX-3.3 (0.5 mM)
      typically block 50% and 65% of Bay K8644-enhanced L-type current, respectively.
      Antagonism of each calcium channel subtype is voltage dependent, with less
      inhibition of Ba2+ currents at more-positive potentials. These data show that
      both sFTX-3.3 and FTX-3.3 antagonize P-, N-, and L-type calcium channels in
      mammalian Purkinje and superior cervical ganglia neurons with similar IC50
      values.

PMID- 8863841
TI  - Voltage-dependent inhibition of Ca2+ channels in GH3 cells by cloned mu- and
      delta-opioid receptors.
AB  - To study cloned opioid receptor binding and modulation of both adenylyl cyclase
      and ion channel activity, we stably expressed mu- and delta-opioid receptors in
      the rodent pituitary-derived GH3 cell line. GH3 cells express G proteins and
      voltage-activated Ca2+ channels (predominantly of the L-type). Activation of
      cloned rat mu-opioid receptors expressed in GH3 cells (termed GH3MOR cells)
      inhibits L-type Ca2+ channel activity. GH3MOR cells, further transfected with
      mouse delta receptor cDNA (termed GH3MORDOR cells), bound both [D-Ala2,N
      MePhe4,Gly-ol5]enkephalin (DAMGO) and [D-Pen2,D-Pen5]enkephalin (DPDPE). These
      opioid ligands inhibited adenylyl cyclase activity (IC50 = 174 and 0.53 nM,
      respectively). This action of DAMGO and DPDPE was attenuated selectively by mu-
      and delta-opioid receptor-specific antagonists. Activation of both opioid
      receptors also led to inhibition of Ca2+ channel activity, measured with Ba2+ as
      the charge carrier using the whole-cell patch-clamp technique. Both DAMGO (1
      microM) and DPDPE (1 microM) reversibly inhibited Ba2+ currents (by 17.0 +/- 1.4%
      and 20.7 +/- 1.3%, respectively) in GH3MORDOR cells. The inhibitory action of
      DPDPE was dose dependent (IC50 = 1.6 nM) and was attenuated by pretreatment with
      pertussis toxin (200 ng/ml) or by the inclusion of guanosine-5'-O-(2
      thio)diphosphate (2 mM) in the recording electrode. Ba2+ current inhibitions by
      both DAMGO and DPDPE were completely reversed by depolarizing (to > 50 mV)
      prepulses in GH3MORDOR cells. In summary, cloned mu- and delta-opioid receptors
      expressed in GH3 cells voltage-dependently couple through Gi/G(o) proteins to L
      type Ca2+ channels.

PMID- 8863842
TI  - Identification of a single amino acid, phenylalanine 586, that is responsible for
      high affinity interactions of tricyclic antidepressants with the human serotonin
      transporter.
AB  - When assayed in parallel using transfected mammalian cells, human and rat
      serotonin transporters (SERTs) exhibit consistent differences in potency for
      tricyclic antidepressants but not for 5-hydroxytryptamine, cocaine, or
      nontricyclic serotonin transporter-selective reuptake inhibitors. Previously,
      using chimeric proteins, we determined that domains or residues distal to
      transmembrane domain 11 (amino acid 531) dictate the increased sensitivity of
      human SERT to imipramine. Using an additional chimera and site-directed
      mutagenesis, we have determined that a single amino acid, F586, is responsible
      for increased sensitivity to imipramine, desipramine, and nortriptyline. Thus,
      mutation of wild-type rat SERT (V586) to the human SERT identity F586, but no
      other divergent amino acids between human and rat SERTs, selectively increased
      tricyclic antidepressant potency. A reciprocal reduction in potency was observed
      when human SERT F586 was converted to the cognate rat SERT residue (V586).
      Interactions with other SERT antagonists, including paroxetine and cocaine, as
      well as the SERT substrates 5-hydroxytryptamine and d-amphetamine were unaffected
      by interconversion of this residue. Phenylalanine conversion in the human
      norepinephrine transporter at the homologous position failed to alter tricyclic
      inhibition of catecholamine uptake, revealing a SERT-specific context for use of
      the aromatic side chain at this position. Additional constraints on aromaticity
      at rat SERT position 586 were revealed by conversion of rat SERT V586 to Y586,
      which failed to repllcate the effect of the F586 mutation. In addition,
      conversion to V586D, but not V586R, increased tricyclic potency to that of human
      SERT and additionally increased potency for cocaine but not paroxetine. These
      results implicate distal domains and a single residue in TMD 12 in the formation
      of high affinity SERT antagonist binding sites.

PMID- 8863844
TI  - Radioligand-dependent discrepancy in agonist affinities enhanced by mutations in
      the kappa-opioid receptor.
AB  - A series of kappa/mu receptor chimeras and a number of kappa receptors
      substituted in the second transmembrane segment (TM-II) were investigated using
      as radioligands, respectively, the kappa-selective agonist [3H]C1977 and the
      nonselective opioid antagonist [3H]diprenorphine (DIP). All of the receptor
      constructs bound [3H]DIP with similar and high affinity, whereas the apparent
      affinity of the nonpeptide agonist C1977, when estimated in competition binding
      with the antagonist [3H]DIP, was impaired between 42- and > 500-fold in the
      kappa/mu chimeras and between 64- and 153-fold in three of the kappa receptor
      mutants that had been substituted in the TM-II segment. However, homologous
      competition binding experiments, using [3H]C1977 as radioligand, showed that the
      high affinity binding of this nonpeptide agonist was in fact not impaired in four
      of the kappa/mu chimeras and in three TM-II substituted kappa receptors compared
      with the wild-type kappa receptor. In all cases in which mutations decreased the
      apparent affinity of C1977 without affecting its actual affinity, as determined
      in homologous assays using [3H]C1977, the calculated number of receptor sites
      (Bmax) was decreased. In three of the kappa/mu constructs, binding of [3H]C1977
      was undetectable, indicating that in these chimeras the affinity of the
      nonpeptide agonist had actually been affected. Also, for the kappa-selective
      peptide agonist dynorphin A(1-8), the measured affinity for the receptor mutants
      was strongly dependent on whether it was determined using the antagonist [3H]DIP
      or the agonist [3H]C1977 in that < or = 800-fold higher Ki values were determined
      in competition with the antagonist. It is concluded that mutations in the kappa
      opioid receptor can cause large discrepancies between the affinity determined for
      agonists in homologous versus heterologous competition binding assays and that
      this pattern, which is compatible with a partial uncoupling of receptors, is
      observed in surprisingly many types of receptor mutations.

PMID- 8863843
TI  - Sensitization of endogenous and recombinant adenylate cyclase by activation of D2
      dopamine receptors.
AB  - Prolonged stimulation of Gi-coupled receptors often sensitizes adenylate cyclase
      to subsequent activation by forskolin or Gs-coupled receptors. To identify
      mechanisms of heterologous sensitization, we characterized sensitization of cAMP
      accumulation that was induced by activation of recombinant dopamine D2 receptors
      expressed in C6 glioma and human embryonic kidney (HEK)293 cells. Pretreatment
      with dopamine or other agonists for 2 hr induced heterologous sensitization that
      was blocked by the D2 antagonist spiperone but not by the beta-adrenergic
      receptor antagonist propranolol. Sensitization was evident after 15 min of
      treatment with dopamine and persisted for at least 2 hr after washout. The EC50
      value for sensitization by dopamine in HEK-D2L cells was 100 nM(r) approximately
      80-fold higher than the IC50 value for dopamine inhibition of cAMP accumulation.
      The D2 receptor agonists quinpirole, 7-hydroxy-dipropylamin-otetralin, and
      pergolide also induced sensitization, whereas the high affinity ergot agonists
      bromocriptine and lisuride did not. Stimulation of either D2L or D2S receptors
      sensitized cAMP accumulation to similar extents, but stimulation of D3 receptors
      did not. In C6-D21 cells, sensitization of isoproterenol-stimulated activity was
      manifested as a > 100% increase in maximal response, with no change in potency.
      In contrast, the potency for forskolin-stimulated activity was increased 4-fold,
      with no apparent change in maximal response. Overnight treatment with pertussis
      toxin (25 ng/ml) had little effect on isoproterenol or forskolin activation of
      adenylate cyclase per se but prevented D2 receptor-mediated sensitization in both
      C6-D2L and HEK-D2L cells, indicating an involvement of one or more of the
      pertussis toxin-sensitive G proteins, Gi/Gzero. D2 receptor stimulation also
      sensitized type I and type II adenylate cyclases, each expressed in HEK293 cells
      together with D2L dopamine receptors. Rapid D2 receptor-mediated heterologous
      sensitization may be the result of enhanced interaction of G6 with adenylate
      cyclase and may represent a novel mechanism for modulation of neural activity by
      D2 receptors.

PMID- 8863845
TI  - Identification of the critical domains of the delta-opioid receptor involved in G
      protein coupling using site-specific synthetic peptides.
AB  - A large body of evidence implicates the second and third intracellular loops and
      the carboxyl-terminal portion of many G protein-coupled receptors as sites
      responsible for the interaction to G proteins. We synthesized a number of
      peptides from selected sites of the murine delta-opioid receptor and measured
      their ability to modify ligand-stimulated G protein activation and 3H agonist
      binding to the receptor. In membranes from Rat-1 fibroblasts transfected to
      express the murine delta-opioid receptor stably (clone D2 cells), the delta
      opioid agonist [D-Ser2-Leu5-Thr6]enkephalin (DSLET) stimulated high affinity
      GTPase activity, which was inhibited by peptides that are derived from the
      proximal (i3.1) and the distal portions (i3.3) of the third intracellular loop
      with IC50 values of 15 +/- 5 and 50 +/- 4 microM, respectively. Peptides i3.1 and
      i3.3 inhibited DSLET-stimulated [35S]guanosine 5'-O-thiotriphosphate binding in
      the same membranes. However, a peptide designated i4, which was derived from a
      juxtamembranous region of the carboxyl-terminal tail of the delta-opioid
      receptor, failed to alter agonist-mediated high affinity GTPase activity or
      agonist-driven [35S]guanosine 5'-O-thiotriphosphate binding. Specific binding of
      [3H]DSLET to membrane preparations from clone D2 was reduced by peptides i3.1 and
      i4. Combinations of these peptides abolished detectable [3H]DSLET binding in the
      same membranes. Peptides i3.1 and i3.3 also destabilized the high affinity state
      of the receptor as assessed in 3H agonist binding on membranes from neuroblastoma
      X glioma (NG108-15) hybrid cells, which express the delta-opioid receptor
      endogenously; furthermore, delta-opioid receptor-stimulated GTPase activity in
      the same membranes was inhibited by peptides i3.1 and i3.3 but i4 was inactive.
      In contrast, peptides derived from the second intracellular loop (i2.1 and i2.2),
      an intermediate portion of the third intracellular loop (i3.2), and the extreme
      amino-terminal region of the receptor were without effect in these assays. These
      observations indicate that although peptides i3.1, i3.3, and i4 act via different
      mechanisms, they provide evidence that at least two sites of the third
      intracellular loop and part of the carboxyl-terminal tail of the delta-opioid
      receptor are important in the interaction between this receptor and cellular G
      proteins. Collectively, these results provide novel information about regions of
      the delta-opioid receptor that are involved in G protein coupling and high
      affinity agonist binding.

PMID- 8863846
TI  - The antioxidant function of the physiological content of vitamin C.
AB  - The synthesis of vitamin C is substantially reduced in Osteogenic Disorder
      Shionogi (ODS) rats. Hepatocytes prepared from these rats contained approximately
      12% of the wild-type content of this vitamin. In culture, the ascorbate content
      remained low in the absence of supplementation of the medium. Independent of
      their vitamin C status, cultured hepatocytes become depleted of vitamin E.
      Supplementation of the culture medium with 10C microM ascorbate and 1.2 microM
      alpha-tocopherol phosphate maintained the physiological content of both vitamins
      C and E in ODS hepatocytes. Thus, the antioxidant function of vitamins C and E
      could be evaluated in the presence of both or either vitamin or in the absence of
      both vitamins. Hepatocytes deficient in both vitamins were the most susceptible
      to lipid peroxidation (as measured by thiobarbituric acid) and to cell kllling
      within a 90-min exposure to 125-500 microM tert-butyl hydroperoxide (TBHP).
      Supplementation to achieve a physiological content of both vitamins C and E
      reduced the evidence of lipid peroxidation and abolished the cell killing.
      Supplementation with either vitamin alone resulted in an intermediate degree of
      both lipid peroxidation and cell killing. In ODS hepatocytes treated with TBHP,
      the decline in vitamin E preceded the decline in vitamin C. In ODS hepatocytes
      depleted of vitamin C, the loss of vitamin E after exposure to TBHP was greater
      than that in the presence of physiological levels of ascorbate. This greater loss
      of vitamin E in the face of a depletion of vitamin C was readily attributable to
      the increased peroxidation of lipids. Thus, the physiological level of vitamin C
      in cells does not seem to regenerate vitamin E. In contrast, the rate and extent
      of the depletion of vitamin C correlate with the degree of cell killing. These
      data document the antioxidant function of the physiological level of cellular
      vitamin C and relate this function to protection against peroxidative cell
      injury.

PMID- 8863847
TI  - Mechanism of extracellular ATP-induced proliferation of vascular smooth muscle
      cells.
AB  - The mitogenic effect of extracellular ATP was examined in cultured rat aortic
      smooth muscle cells (VSMCs). ATP, 2-methylthio-ATP, and ADP stimulated
      [3H]thymidine and [3H]leucine incorporation and cell growth. AMP, adenosine, UTP,
      and P2x agonists showed little of these effects. Reactive blue 2, a P2Y
      purinoceptor antagonist, was effective in suppressing the mitogenic effect of ATP
      and 2-methylthio-ATP, indicating that extracellular ATP-induced VSMC
      proliferation is mediated by P2Y purinoceptors. The P2Y purinoceptor activation
      was coupled to a pertussis toxin (PTX)-insensitive G protein (Gq) and triggered
      phosphoinositide hydrolysis with subsequent activation of protein kinase C (PKC),
      Raf-1, and mitogen-activated protein kinase (MAPK) in VSMCs. In response to ATP,
      both 42-and 44-kDa MAPKs were activated, and tyrosine was phosphorylated. Western
      blot analysis using PKC isozyme-specific antibodies indicated that VSMCs express
      PKC-alpha, PKC-delta, and PKC-zeta. A complete down-regulation of PKC-alpha and
      PKC-delta was seen after 24-hr treatment with 12-O-tetradecanoylphorbol-13
      acetate. When cells were pretreated with 12-O-tetradecanoyl-phorbol-13-acetate
      for 24 hr and subsequently challenged with ATP, Raf-1 activation and 42-kDa as
      well as 44-kDa MAPK tyrosine phosphorylation failed to be induced. These results
      demonstrate that ATP-induced Raf-1 and MAPK activations involve the activation of
      PKC-alpha and PKC-delta. P2Y purinoceptor stimulation with ATP also caused
      accumulation of c-fos and c-myc mRNAs. Both Reactive blue 2 and staurosporine
      significantly blocked this increase by ATP. In conclusion, the mitogenic effect
      of ATP seemed to be triggered by activation of the Gq protein-coupled P2Y
      purinoceptor that led to the formation of inositol trisphosphate and activation
      of PKC. PKC and, in turn, Raf-1 and MAPK were then activated, leading eventually
      to DNA synthesis and cell proliferation.

PMID- 8863848
TI  - Ethanol inhibition of nicotinic acetylcholine type alpha 7 receptors involves the
      amino-terminal domain of the receptor.
AB  - Recent studies have suggested that alcohols can affect the function of
      neurotransmitter-gated ion channels by a direct interaction with the receptor
      protein. However, the molecular region of the receptor protein that mediates the
      alcohol action is not known. To address this question, we studied the effect of
      ethanol on the function of recombinant nicotinic acetylcholine type alpha 7 (nACh
      alpha 7) receptors, 5-hydroxytryptamine (serotonin) type 3 (5-HT3) receptors, and
      a chimeric receptor constructed from these two receptors. The receptors were
      expressed in Xenopus oocytes and their function was studied using the two
      electrode voltage-clamp technique. Ethanol inhibited the response of nACh alpha 7
      receptors in a concentration-dependent manner over the concentration range of 5
      100 mM; the EC50 for this inhibition was 33 mM ethanol. Ethanol decreased the
      maximal amplitude (Emax) of the nACh alpha 7 receptor agonist concentration
      response curve, without significantly affecting the EC50. In contrast, ethanol
      potentiated 5-HT3 receptor-mediated responses at low agonist concentrations. The
      potentiation was concentration-dependent over the concentration range of 10-100
      mM; the EC50 for this potentiation was 57 mM ethanol. The magnitude of the
      ethanol potentiation of 5-HT3 receptor-mediated responses decreased with
      increasing agonist concentration. The chimeric receptor had the amino-terminal
      domain from the nACh alpha 7 receptor and the transmembrane and carboxyl-terminal
      domains from the 5-HT3 receptor. Ethanol was found to inhibit the function of
      this chimeric receptor in a manner similar to that of nACh alpha 7 receptors.
      Because the inhibition transfers with the amino-terminal domain of the receptor,
      the observations suggest that the amino-terminal domain of the receptor is
      involved in the inhibition.

PMID- 8863849
TI  - 5-hydroxytryptamine2C receptor activation inhibits 5-hydroxytryptamine1B-like
      receptor function via arachidonic acid metabolism.
AB  - We previously reported that in Chinese hamster ovary (CHO) cells, 5
      hydroxytryptamine (5-HT)1B-like (CHO/5-HT1B) receptor-mediated inhibition of
      forskolin-stimulated cAMP accumulation is inhibited by activation of transfected
      human 5-HT2C receptors but not 5-HT2A receptors. In the current study, we
      investigated the mechanism involved in the regulation of receptor-mediated
      inhibition of adenylyl cyclase as a means to further elucidate differences
      between the signal transduction cascades of the 5-HT2A and 5-HT2C receptor
      subtypes. Activation of 5-HT2C receptors with 5-HT or (+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane increased release of arachidonic acid via a
      phospholipase A2 (PLA2)-dependent mechanism. Incubation with (+/-)-1-(2,5
      dimethoxy-4-iodophenyl)-2-aminopropane (1 microM) abolished 5
      carboxamidotryptamine (5 nM)-mediated inhibition of forskolin-stimulated cAMP
      accumulation, which was blocked by the PLA2 inhibitor mepacrine (100 microM) and
      the cyclooxygenase inhibitor indomethacin (2 microM). Furthermore, purinergic
      receptor-mediated PLA2 activation as well as direct activation of PLA2 with
      melittin reduced CHO/5-HT1B responsiveness. These data indicate that activation
      of the PLA2/arachidonic acid signaling cascade mediates 5-HT2C receptor
      regulation of the CHO/5-HT1B receptor pathway. Consistent with our previous
      report and in contrast to activation of 5-HT2C or purinergic receptors,
      activation of 5-HT2A receptors had no effect on CHO/5-HT1B receptor function,
      although 5-HT2A receptor-mediated activation of PLA2 was measured. Interestingly,
      purinergic receptor-mediated inhibition of CHO/5-HT1B receptor function was
      blocked when 5-HT2A receptors were activated simultaneously. These data suggest
      that the lack of 5-HT2A mediated regulation of CHO/5-HT1B receptors may be due to
      activation of a third pathway (in addition to PLC and PLA2 pathways), which
      results in the inhibition of the production or the actions of a cyclooxygenase
      dependent arachidonic acid metabolite.

PMID- 8863850
TI  - Design and in vitro pharmacology of a selective gamma-aminobutyric acidC receptor
      antagonist.
AB  - In mammals, receptors for the inhibitory neurotransmitter gamma-aminobutyric acid
      (GABA) are divided into three pharmacological classes, which are denoted GABAA,
      GABAB, and GABAC. GABAC receptors are defined by their insensitivity to the GABAA
      receptor antagonist bicuculline and the GABAB receptor agonist (-)-baclofen.
      GABAC receptors probably are a heterogeneous group of proteins. The most
      extensively studied mammalian GABAC receptors are those found in neurons of the
      outer retina. These receptors are GABA-gated Cl- channels comprised of p
      subunits, of which there are two subtypes. The physiological functions served by
      GABAC receptors are largely unknown; to determine the functions, it would be
      useful to have GABAC-selective ligands. In a previous study, we found that
      isoguvacine, a GABAA-selective agonist, and 3-aminopropyl-(methyl)phosphinic acid
      (3-APMPA), a GABAB-selective agonist, show affinity for retinal GABAC receptors.
      In particular, 3-APMPA is an antagonist with low micromolar potency (Kb
      approximately 1 microM). Here, we report the synthesis and pharmacological
      characterization of (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid
      (TPMPA), a hybrid of isoguvacine and 3-APMPA designed to retain affinity for
      GABAC receptors but not to interact with GABAA or GABAB receptors. Electrical
      assays show that TPMPA is a competitive antagonist of cloned human mu 1 GABAC
      receptors expressed in Xenopus laevis oocytes (Kb approximately 2 microM). TPMPA
      is > 100-fold weaker as an inhibitor of rat brain GABAA receptors expressed in
      oocytes (Kb approximately 320 microM) and has only weak agonist activity on GABAB
      receptors assayed in rat hippocampal slices (EC50 approximately 500 microM).
      TPMPA should be a useful pharmacological probe with which to investigate GABAC
      receptor function in the outer retina and in any other areas of the nervous
      system in which these types of receptor are present.

PMID- 8863851
TI  - Two Gs-coupled prostaglandin E receptor subtypes, EP2 and EP4, differ in
      desensitization and sensitivity to the metabolic inactivation of the agonist.
AB  - There are at least four subtypes of prostaglandin E (PGE) receptors. The EP1 and
      EP3 receptors are coupled to Ca2+ mobilization and the inhibition of adenylate
      cyclase, respectively, and the EP2 and EP4 receptors are coupled to the same
      signal transduction pathway, stimulation of adenylate cyclase. To identify the
      functional differences between EP2 and EP4 receptors, we examined agonist-induced
      desensitization of these two receptors using Chinese hamster ovary cells, which
      stably express these receptors. The EP4 receptor underwent short term agonist
      induced desensitization, but no such desensitization was observed for the EP2
      receptor. In contrast, the EP2 and EP4 receptors displayed similar patterns of
      down-regulation in response to prolonged exposure to PGE2. On the other hand,
      PGE2 is rapidly metabolized to 15-keto-PGE2 and, subsequently, to 13,14-dihydro
      15-keto-PGE2. Thus, we compared the sensitivities of the two receptors to these
      two metabolites. The EP4 receptor markedly lost the response at the first
      metabolism, whereas the EP2 receptor gradually lost the response according to the
      degree of metabolism, having higher sensitivity to the first metabolite, 15-keto
      PGE2, than the EP4 receptor. Therefore, the physiological significance of EP2 and
      EP4 may lie in their different sensitivities to agonist-induced short term
      desensitization and their differential susceptibilities to the metabolic
      inactivation of the agonist.

PMID- 8863852
TI  - m3 Muscarinic receptor-induced and Gi-mediated heterologous potentiation of
      phospholipase C stimulation: role of phosphoinositide synthesis.
AB  - Agonist activation of thrombin and purinergic receptors endogenously expressed in
      human embryonic kidney (HEK) cells and of the stably expressed m3 muscarinic
      acetylcholine receptor (mAChR) induces phospholipase C (PLC) stimulation, with
      the most pronounced PLC stimulation observed on mAChR activation. These receptor
      responses were pertussis toxin (PTX) insensitive and nonadditive, suggesting that
      the receptors share common signaling pathways. Short term (2 min) pretreatment of
      HEK cells with carbachol (1 mM), but not ATP, followed by agonist washout, caused
      a long-lasting (> or = 90 min) sensitization of PLC responses. At 30 min after
      carbachol treatment and washout, mAChR-stimulated PLC activity, measured as
      formation of either total inositol phosphates or of inositol-1,4,5-trisphosphate,
      was enhanced by 1.5-2-fold. PLC stimulation by thrombin and purinergic receptors
      was increased by approximately 3-fold. Furthermore, carbachol pretreatment also
      enhanced, by approximately 2.5-fold, stimulation of PLC activity on direct
      activation of G proteins by AIF4- and guanosine-5'-O-(3-thio)-triphosphate in
      intact and permeabilized cells, respectively. In contrast, PLC activities,
      measured with exogenous phosphatidylinositol-4,5-bisphosphate [Ptdns(4,5)P2] in
      HEK cell lysates, were not altered, suggesting that carbachol pretreatment may
      enhance the cellular level of Ptdlns(4,5)P2. Indeed, the level of Ptdlns(4,5)P2
      was found to be increased by approximately 50% in HEK cells 30 min after short
      term carbachol treatment, whereas the level of phosphatidylinositol was not
      altered and that of phosphatidylinositol-4-phosphate decreased (by 40-50%).
      Pretreatment of HEK cells with PTX prevented the m3 mAChR-induced PLC
      potentiation and reduced the elevation in Ptdlns(4,5)P2 level by approximately
      50%. In conclusion, short term agonist activation of m3 mAChRs stably expressed
      in HEK cells can lead to a longlasting heterologous potentiation of PLC
      signaling, which processes apparently involve PTX-sensitive G proteins and an
      enhanced PLC substrate supply.

PMID- 8863853
TI  - Pituitary adenylate cyclase-activating peptide, carbachol, and glucose stimulate
      insulin release in the absence of an increase in intracellular Ca2+.
AB  - Insulin secretion from the pancreatic beta cell line HIT-T15 was examined under
      conditions in which the elevation of intracellular free Ca2+ concentration
      ([Ca2+]i) was inhibited by nitrendipine or diazoxide or by severe Ca2+
      deprivation. Glucose-induced insulin release was completely abolished under these
      conditions. However, in the presence of 12-O-tetradecanoyl-phorbol-13-acetate or
      forskolin, 10 mM glucose significantly enhanced insulin release, even in the
      presence of 5 microM nitrendipine or 150 microM diazoxide. The [Ca2+]i was not
      increased under these conditions. Even under Ca(2+)-deprived conditions, achieved
      by 60-min preincubation in Ca(2+)-free buffer containing 1 mM ethylene glycol bis
      (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), glucose in the
      complete absence of extracellular Ca2+ significantly enhanced insulin release
      when the cells were treated also with 12-O-tetradecanoylphorbol-13-acetate and
      forskolin. Because of these findings, additional studies were performed with
      pituitary adenylate cyclase-activating peptide (PACAP) and carbachol to see
      whether physiological stimulation via receptor activation could stimulate insulin
      release in the absence of a rise in [Ca2+]i. Under normal Ca(2+)-containing
      conditions, PACAP and carbachol stimulated insulin release and markedly
      potentiated glucose-stimulated release. In the presence of nitrendipine and
      thapsigargin, glucose failed to stimulate insulin release. Also, neither glucose
      in combination with PACAP nor glucose with carbachol was able to stimulate
      release. However, under the same conditions, the combination of glucose, PACAP,
      and carbachol did stimulate release while being unable to elevate [Ca2+]i. Thus,
      simultaneous activation of the beta cell by PACAP, carbachol, and glucose can
      stimulate insulin release even when [Ca2+]i is not elevated.

PMID- 8863854
TI  - Colocalisation of NADPH-diaphorase with neuropeptides in the ureterovesical
      ganglia of humans.
AB  - Neurones in the ureterovesical ganglion complex provide autonomic innervation to
      the pelvic ureter, the ureterovesical junction and the bladder trigone. We
      examined the distribution and peptide co-expression pattern of nitric oxide
      synthase (NOS) in the human ureterovesical ganglia by combining NADPH-diaphorase
      histochemistry with immunoreactivity for vasoactive intestinal peptide (VIP),
      neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP). Less than 20%
      of nerve cells in the large ganglia of the ureterovesical complex were stained
      for NOS activity. In elderly individuals, ganglion cells regularly exhibited
      conspicuous morphological alterations suggestive of degenerative changes. Most of
      the NOS-positive cell bodies costained for VIP-immunoreactivity. A minority of
      NOS-expressing cells also reacted for NPY-immunoreactivity. CGRP-immunoreactivity
      was present in varicose terminal-like nerve fibres which were found to encircle
      NOS-containing perikarya. Occasionally, NOS-positive somata were surrounded by
      plexiform axon terminals which immunostained for VIP or NPY. We conclude that the
      passage of urine across the ureterovesical junction is under relaxatory control
      of a local nitric oxide/VIP(NPY) pathway which may be modulated by preganglionic
      efferent and/or primary afferent input.

PMID- 8863855
TI  - Hypoxia-dependent changes of enzyme activities in different fibre types of rat
      soleus and extensor digitorum longus muscles. A cytophotometrical study.
AB  - Using cytophotometry activity changes of succinate dehydrogenase, glycerol-3
      phosphate dehydrogenase and myofibrillar adenosine triphosphatase were measured
      in 3 fibre types of soleus and extensor digitorum longus muscles under normal and
      experimental conditions. Fibres were typed by means of cytophotometrical data
      into slow-oxidative, fast-oxidative glycolytic and fast-glycolytic ones. After
      experimental hypoxia of 20 min duration a significant increase of enzyme
      activities was observed especially in slow-oxidative and fast-oxidative
      glycolytic fibres of both muscles, e.g. succinate dehydrogenase activity
      increased by 21% in these fibres of soleus muscle and by 23-26% in these fibres
      of extensor digitorum longus muscle. Moreover, an increase of glycerol-3
      phosphate dehydrogenase activity by 10% in slow-oxidative fibres and by 28% in
      fast-oxidative glycolytic fibres and a 10-12% increased ATPase activity in all
      fibres of extensor digitorum longus muscle were measured. Treatment with Ginkgo
      biloba extract for 3 months before exposure to hypoxia resulted in increased
      adenosine triphosphatase activity in all fibres of both muscles and in decreased
      succinate dehydrogenase activity of slow-oxidative and fast-oxidative glycolytic
      fibres of extensor digitorum longus muscle. These results could be interpreted as
      a protective effect of Ginkgo biloba extract.

PMID- 8863856
TI  - Ultrastructural sinusoidal changes in extrahepatic cholestasis. Light and
      electron microscopic immunohistochemical localization of collagen type III and
      type IV.
AB  - Extrahepatic cholestasis causes excessive extracellular matrix formation
      perisinusoidally. Ito cells, transitional and endothelial cells are considered to
      be a source of extracellular matrix proteins in experimental cholestasis. The
      localization of collagens type III and type IV in human liver in extrahepatic
      cholestasis was investigated immunohistochemically in the present study.
      Immersion fixation was used after modification to be applied to surgical biopsies
      with commercially available kits. Sinusoidal changes were observed that indicated
      excessive collagen and matrix formation. Light microscopically, increased
      immunostaining with the two collagen antibodies was found perisinusoidally and
      portally. Ultrastructurally, collagen type III positive fibres were found beneath
      basement membranes of vessels, in collagen bundles and as a fibrillar network in
      the space of Disse. Collagen type IV immunostaining was located in portal tracts
      and near hepatocyte microvilli. Intracellular staining with collagen type IV was
      detected in the rough endoplasmic reticulum of some transitional cells.
      Immunostaining was located around transitional cells, Ito cells or endothelial
      cells mainly. Our study indicates that Ito cells, transitional and endothelial
      cells are the main source of collagens type III and IV in the space of Disse in
      extrahepatic cholestasis in humans.

PMID- 8863857
TI  - Sucrase-isomaltase and other brush border glycosidases in colorectal tumors.
AB  - Sucrase-isomaltase (SI), trehalase (T) and lactase-beta-glucosidase (LG)
      activities were assessed histochemically in samples of colorectal adenomas (11
      tubular, 12 tubulovillous, 10 villous) and 30 adenocarcinomas obtained by biopsy
      during colonoscopy or from specimens removed by surgical intervention. Small
      samples of tumor tissue, tissue of the transitional zone and of macroscopically
      normal mucosa were quenched in heptan cooled in an acetone-dry ice mixture.
      Cryostat sections, transferred to non-precooled slides and in some cases to
      semipermeable membranes, were dried and subjected to the histochemical reactions
      for SI, T and LG. Sucrose, 2-naphthyl, 6-Br-2-naphthyl, and 5-Br-4-Cl-3-indoxyl
      alpha-D-glucosides, trehalose, and 5-Br-4-Cl-3-indoxyl-beta-D-fucoside were used
      as substrates. Sections of jejunal biopsies with normal activities of brush
      border glycosidases were used as controls. From samples of 5 adenomas, 5
      adenocarcinomas and collected rests of jejunal biopsies with a normal finding 10%
      (w/vol) homogenates in 2% Triton X-100 were prepared. Homogenates were frozen and
      thawed 3 times and their supernatants subjected to isoelectric focusing on
      polyacrylamide gel plates. Zymograms were developed with the same methods as for
      the detection of alpha-glucosidases in sections. In no colorectal tumor LG was
      present. SI was found in 70% adenocarcinomas, 50% villous, 25% tubulovillous and
      19% tubular adenomas when the method with sucrose, glucose oxidase-peroxidase and
      3,3'-diaminobenzidine was used. Hardly discernible traces of activity were found
      in tumors with azo-coupling reactions applied at pH 5, 6 and 6.5. No reaction was
      detected with the indigogenic method applied at pH above 6.0. However, jejunal
      biopsies displayed very strong reactions confined to the brush border of
      enterocytes under the same conditions. A strongly positive reaction was seen in 7
      of 12 tumors investigated recently when the indigogenic reaction was applied at
      pH below 6.0 (particularly at pH 5.0). In this case the deposition of indigo was
      due to membrane and lysosomal alpha-glucosidases of the tumor cells and lysosomal
      alpha-glucosidase of macrophages and leukocytes. These findings were corroborated
      by zymograms. T was detected in the same tumors as SI; its activity was lower,
      however. SI activity in colorectal tumors is a useful, but not general marker of
      these tumors.

PMID- 8863858
TI  - Desktop computer-based image analysis of cell surface fluorescence patterning
      from a photographic source.
AB  - We report the use of standard computer-based image analysis technology to
      analyze, from a photographic source, individual cell surface receptor site
      patterns using fluorochrome labeling. The model used in this study was a
      Strongylocentrotus purpuratus sea urchin embryo labeled with fluorescein
      isothiocyanate-conjugated wheat germ agglutinin (FITC-WGA) (0.5 mg/ml for 5 min
      at 15 degrees C incubated with fertilization membrane free embryos). Image
      capture was performed using desktop-type digital scanning, and the images were
      imported into Adobe Photoshop for study. All images analyzed were derived from a
      single photographic negative: 1) the actual micrograph printed from the negative
      and scanned into a Macintosh IIx computer; 2) the scanned negative itself; and,
      3) a high resolution scanning process used with a Kodak Photo CD. Patterns were
      analyzed using the densitometry feature of Photoshop, and were similar enough
      from all 3 scanned images to indicate that any of the 3 scanning processes can be
      used for fluorescence patterning analysis. Adobe Photoshop was also used to
      highlight, for closer analysis, the fluorescence patterns by producing 3-D
      effects, border mapping and transition area detailing. The desktop image analysis
      procedures described here to study fluorescence patterning require no expensive
      scientific hardware or software.

PMID- 8863859
TI  - Immunohistochemical characterization of amyloid fibril precursors in renal
      tissue.
AB  - Amyloidosis is a heterogeneous group of disorders characterised by extracellular
      deposition of abnormal protein fibrils which are derived from different proteins
      in different forms of the disease. Almost all patients with amyloidosis have
      renal disorders. Distinguishing type of amyloidosis is important for therapeutic
      and investigative purposes. The different types of amyloid fibril proteins can be
      evaluated by immunohistochemistry, but not by routine histochemical techniques.
      On the basis of immunohistochemical studies two groups of amyloidosis were
      distinguished. In all cases, whatever the type, P component was detected, while
      none of the biopsies revealed transthyretin. The immunoperoxidase technique has
      the advantage of being able to detect amyloid in formalin-fixed paraffin embedded
      tissues and remains the simplest and very specific method for identifying amyloid
      fibril proteins.

PMID- 8863860
TI  - A light and electron microscopic radioautographic study on RNA synthesis in the
      retina of chick embryo.
AB  - The incorporation of 3H-uridine into RNA of chick embryo retina was studied by
      light and electron microscopic radioautography. The numbers of silver grains were
      counted over the nucleus, nucleolus and cytoplasm of the cells in three different
      regions of the same retina of 2, 3, 4, and 7 day chick embryos. The results
      showed an increase of 3H-uridine incorporation from embryonic day 2 to 7. In
      every stage of development of the chick embryo retina, the number of silver
      grains was higher in the anterior than in the other two regions of the retina. In
      the three cell compartments of every embryo group, the number of silver grains
      was higher in the nucleus than in the nucleolus and cytoplasm. The results show
      further that the grains were less in the cytoplasm of the retinal cells of the
      day 2 embryo group and higher in the other groups especially in the day 7
      embryos. Ultrastructural changes were also observed during the studied period of
      retina development.

PMID- 8863861
TI  - Immunoelectron microscopic single and double labelling of aminopeptidase N (CD
      13) and dipeptidyl peptidase IV (CD 26).
AB  - Using ultrathin cryosections and immunogold labelling, aminopeptidase N (CD 13)
      and dipeptidyl peptidase IV (CD 26) were localized on the luminal side of the
      brush border membrane of proximal tubular cells in human kidney as well as of
      enterocytes from rat small intestine. Furthermore, both enzymes could be detected
      on the cell surface of human T lymphocytes and especially aminopeptidase N on
      human synovial fibroblasts. Gold labelled vesicular structures were also found in
      the cytoplasm in the apical part of renal proximal tubular cells and synovial
      fibroblasts. In human kidney the colocalization of the two membrane antigens was
      possible by using several double labelling methods.

PMID- 8863862
TI  - A multiwell plate procedure for immunohistochemical and histochemical staining of
      constituents of articular cartilage.
AB  - A multiwell plate procedure was tested for its applicability to determine
      immunohistochemically the noncollagenous matrix protein COMP (cartilage
      oligomeric matrix protein) and histochemically the proteoglycans of the matrix of
      articular cartilage. Fixed and decalcified cartilage-bone sections were treated
      with buffer, antisera, substrate or staining solutions in the wells of an assay
      plate under shaking on a rocking table. This floating procedure results in a
      reproducible histochemical or immunohistochemical staining and might therefore be
      valuable to determine or to detect other constituents of the matrix of these
      connective tissues under comparable conditions.

PMID- 8863863
TI  - Adhalin (alpha-sarcoglycan) is not required for anchoring of nitric oxide
      synthase I (NOS I) to the sarcolemma in non-mammalian skeletal (striated) muscle
      fibers.
AB  - Previous studies have shown the association of NOS I with the sarcolemma in
      mammalian striated muscle fibers, implicating the dystrophin complex (DC) as a
      major anchor for the enzyme. The potential role of the sarcoglycan subcomplex,
      especially of alpha-sarcoglycan (adhalin), as part of the DC in holding of NOS I
      in the sarcolemmal position was examined by carrying out a comparative study on
      the distribution of NOS I, dystrophin, dystrophin-associated glycoproteins (DAG)
      and alpha-sarcoglycan in various skeletal muscles of non-mammals. Rat muscles
      were included since they reflect the situation in mammals. Catalytic NOS
      associated diaphorase (NOSaD) activity as well as NOS I and DAG
      immunoreactivities were positive in the saracolemma region of skeletal muscle
      fibers of rats, chicken, and turtles. Adhalin immunoreactivity was present in the
      rat but absent in the chicken and turtle muscle surface membrane. These data
      suggest that alpha-sarcoglycan and therefore the entire sarcoglycan subcomplex
      may not be needed for localizing NOS I to the sarcolemma in these non-mammalian
      species. This may hold for skeletal muscle fibers in general.

PMID- 8863864
TI  - A new model to predict final height in constitutionally tall children.
AB  - In order to develop new height prediction models for children with
      constitutionally tall stature, 55 such boys and 88 girls were recalled for
      measurement of adult final height (FH). Data on height (H), age (CA), and target
      height (TH) were collected from the hospital charts and radiographs of the left
      hand and wrist were retrieved and used for bone age (BA) determination [BA
      according to the methods of Greulich and Pyle (BAGP) and Tanner and Whitehouse
      (BARUS)]. Standard multiple regression techniques were used to develop prediction
      equations for FH. In addition to test the validity of the new equations, FH was
      measured in a second group of constitutionally tall children (n = 32) and
      compared with the predicted FH according to our models. In addition, a comparison
      was made with other prediction methods. Mean (SD) FH was 196.0 (4.9) cm in boys
      and 180.5 (3.8) cm in girls. The ultimate regression equation was FH (cm) =
      216.07 + 0.75 x H + 0.25 x TH -11.09 BAGP + 0.74 x (CA x BAGP) for boys and FH =
      161.42 + 0.73 x H + 0.15 x TH - 8.41 x CA -8.83 x BARUS -2.45 x M + 0.55 x (CA x
      BARUS) for girls. The models showed satisfying accuracy: the mean (SD) errors
      were -1.4(3.2) cm for boys and -0.5(3.1) cm for girls with corresponding mean
      (SD) absolute errors of 2.7 (2.2) cm and 2.0 (2.4) cm, respectively. Compared
      with the current prediction methods, the new models were quite promising. Their
      clinical validity has to be ascertained in larger groups of tall children.

PMID- 8863865
TI  - Low urinary GH levels in normal statured obese children.
AB  - Urinary GH (u-GH) levels were evaluated in 240 children (age range 5-14 years;
      136M, 104F) of normal height (25-90th centile); 165 children were defined as "non
      obese" (body mass index (BMI) < 75th centile for their chronological age (CA))
      and 75 as "obese" (BMI > 75th). U-GH levels were determined using a two-site
      enzyme immunometric assay and calculated as the mean obtained from the values of
      three consecutive first morning voidings; results were expressed as both u-GH
      concentration (ngl-1) and u-GH excretion (ng per night). Multiple regression
      analysis revealed that in all children (non-obese and obese) most of the
      variation in u-GH levels (ngl-1 and ng night-1) was explained by BMI
      (coefficient: -0.72, p < 0.0001 and coefficient: -0.10, p < 0.001, respectively)
      and chronological age (coefficient: 1.03, p < 0.01 and coefficient; 0.27, p <
      0.001, respectively), whereas sex and pubertal stage did not add significance to
      the variance. In obese children, mean u-GH concentration and u-GH excretion (per
      night) levels were significantly lower than those recorded in non-obese children
      both before and during puberty. A similar trend towards higher u-GH levels at
      puberty was found in non-obese and obese children. In conclusion, our study shows
      that u-GH levels are (a) related to CA and BMI in the general population and (b)
      significantly lower in obese than in non-obese children, in spite of their
      comparable normal height. The measurement of u-GH excretion in the assessment of
      children with short stature needs to take into consideration the role of marked
      ponderal excess, which is associated "per se" with significantly lower u-GH
      levels.

PMID- 8863866
TI  - Body composition, atherogenic risk factors and apolipoproteins following growth
      hormone treatment.
AB  - We studied the change in atherogenic risk factors in 27 children, 21 boys and 6
      girls, 6 to 14 years of age, with growth hormone deficiency during 12 months of
      growth hormone replacement therapy. Changes in body composition and lipid profile
      during growth hormone treatment were evaluated. The atherogenic index was
      calculated using the equation [(total cholesterol- high-density lipoprotein
      cholesterol)(apolipoprotein B)]/[(apolipoprotein AI)(high-density lipoprotein
      cholesterol)]. Body fat decreased (p < 0.01), associated with an increase in lean
      body mass (p < 0.01). Total cholesterol and high-density lipoprotein cholesterol
      showed no significant changes. The atherogenic index significantly decreased from
      1.44 +/- 0.60 to 1.09 +/- 0.52 (p < 0.01) after 12 months. Apolipoproteins CII
      and CIII increased throughout the study period (p < 0.01). Lipoprotein(a) and
      apolipoproteins AI, B and B/AI ratio did not change significantly. In conclusion,
      growth hormone treatment improved body composition and reduced atherogenic risk
      factors in children with growth hormone deficiency.

PMID- 8863867
TI  - Cerebrospinal fluid concentrations of leukotriene B4 in bacterial meningitis.
AB  - We investigated whether leukotriene B4 (LTB4), a granulocyte inflammatory
      mediator, is detectable in cerebrospinal fluid using a high performance liquid
      chromatographic method. In non-pleocytotic cerebrospinal fluid (n = 5) and in
      cerebrospinal fluid from children with aseptic meningitis (n = 8), LTB4
      concentrations were below the detection limit (< 0.2 ng ml-1). In the range 0-20
      ng ml-1, the recovery rate of LTB4 that had been added to non-pleocytotic
      cerebrospinal fluid was > 90%. In cerebrospinal fluid with a polymorphonuclear
      leucocyte (PMN) count higher than 1,000/ml, LTB4 was detectable in six out of
      seven specimens with a concentration of 0.35-3.3 ng ml-1. LTB4 concentration was
      significantly correlated with PMN number. These results, together with
      observations in animal models, are discussed with regard to a pathophysiological
      role of LTB4 in bacterial meningitis.

PMID- 8863868
TI  - Age-dependent variation in the serum concentration of mannan-binding protein.
AB  - Mannan-binding protein (MBP) is an acute phase reactant, and its deficiency is
      associated with the common opsonic defect and suspectibility to infections and
      atopic constitution. The aim of this study was to investigate the changes
      occurring in the serum level of MBP in infancy and during later childhood. We
      studied the serum concentration of MBP in 611 Finnish children of different ages
      and 110 adults by using an enzyme immunoassay. In an analysis of successive serum
      samples from infants at the day of birth and at the ages of 1 and 5 months, and
      at 1 and 2 years, the serum concentration of MBP increased significantly after
      birth, and was at its highest (the mean and median were 8.13 and 8.49 mgl-1,
      respectively) at the age of 1 month. After that, it declined to the initial level
      until the age of 5 months. The MBP concentration continued to decrease during
      childhood, and after the age of 12 years the MBP values reached the adult level.
      In Finnish adults the mean and median concentrations of MBP were 4.48 and 4.02
      mgl-1, respectively, which seem to be higher than those reported previously in
      other populations. The high concentration of MBP in infants may best be explained
      by exposure to novel environmental antigens in early childhood, which suggests a
      protective role for MBP during the period of immaturity of the immunosystem. In
      older children the high level of MBP can probably be explained by childhood
      infections and the ensuing need of MBP.

PMID- 8863870
TI  - HLA-DP antigens and post-streptococcal acute glomerulonephritis.
AB  - We have typed 58 Japanese patients with post-streptococcal acute
      glomerulonephritis (PSAGN) for HLA-DRB1, DQA1, DQB1, DPA1, and DPB1 genes by the
      HLA-DNA typing method using a polymerase chain reaction (PCR)-sequence specific
      oligonucleotide probe (SSOP) technique. The control subjects were 317 healthy
      unrelated individuals. Frequencies of HLA-DPA1 02022 and DPB1 0501, which are in
      linkage disequilibrium and encode HLA-DP5 antigen, were significantly increased
      in patients with PSAGN than those in control (pc < 0.0005 and pc < 0.005,
      respectively). Frequencies of HLA-DPA1*01 and DPA1*0201 were significantly
      decreased in patients when compared with controls (pc < 0.05, for both). No
      significant difference in allele frequencies between the two groups was observed
      in the DRB1, DQA1 and DQB1 genes. This is the first report documenting the
      association of HLA-DP alleles with PSAGN. We speculate that HLA-DP5 antigens may
      be involved in the development of PSAGN.

PMID- 8863869
TI  - Randomized trial comparing intravenous immunoglobulin with methylprednisolone
      pulse therapy in acute idiopathic thrombocytopenic purpura. Danish I.T.P. Study
      Group.
AB  - Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura
      (ITP), platelet count (PC) below 20 x 10(9)l-1, and either continued bleeding or
      failure to show a spontaneous rise in the PC after a 3 day observation period
      were randomized to treatment with either intravenous immunoglobulin (IVIG)
      infusions 1 g kg-1 (n = 23) or intravenous methylprednisolone pulse therapy
      (MPPT) 30 mg kg-1 (n = 20) on two consecutive days. After 72 h, IVIG had induced
      greater platelet responses (mean PC 188 x 10(9) versus 77 x 10(9)l-1, 2p < 0.001)
      and raised the PC to a haemostatically safe level above 50 x 10(9)l-1 more
      frequently (91 versus 50%, one-sided exact p = 0.003). Children responding poorly
      were then given the alternative treatment in addition. After 6 days, a normal PC
      of over 150 x 10(9)l-1 had been obtained more frequently in the group given first
      line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow
      up were not significantly different (26 versus 40%, p = 0.26). Cross-over
      treatment in 11 children with relapse confirmed the superior response to IVIG.
      The treatment given was restricted to the two initial infusions more often in the
      IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be
      preferable to MPPT as the initial treatment for ITP.

PMID- 8863871
TI  - Altered Na(+)-K+ ATPase activity in uraemic adolescents.
AB  - The Na(+)-K+ ATPase enzyme plays an essential role in the regulation of cell
      composition and volume. Enzyme activity itself is regulated by substrate
      availability and several hormones. In adult uraemic patients red blood cell Na(+)
      K+ ATPase activity is decreased. However, it is unknown if children with uraemia
      exhibit the same phenomenon. Therefore, in the present study we examined whether
      endogenous digoxin-like factors (EDLF) and physicochemical membrane properties
      play a role in the regulation of erythrocyte Na(+)-K+ ATPase activity in uraemic
      children and adolescents. Healthy age-matched children were used as controls.
      Enzyme activity was measured in detergent-pretreated red blood cells and
      erythrocyte ghosts. Na(+)-K+ ATPase activity (2204 +/- 538 nmol Pi ml erythrocyte
      1 h-1 in detergent pretreated erythrocytes; 204 +/- 56 nmol Pi mg protein-1 h-1
      in ghosts) in adolescents with uraemia was lower compared to controls (3245 +/-
      362 nmol Pi ml erythrocyte-1 h-1; 266 +/- 37 nmol Pi mg protein-1 h-1, p < 0.001,
      p < 0.05, respectively). Plasma levels of EDLF were elevated in uraemic patients
      (0.30 +/- 0.05 versus 0.21 +/- 0.04 ng ml-1, p < 0.01). Furthermore, the membrane
      lipid component was decreased in patients with uraemia, while the
      cholesterol/phospholipid ratio and membrane fluidity were similar in both groups.
      No correlation was found between the decrease in Na(+)-K+ ATPase and the increase
      in EDLF concentration and altered membrane lipid components. Our results
      demonstrate, that similar to the findings of adults, the activity of Na(+)-K+
      ATPase is diminished in uraemic adolescent patients, and that uraemia-associated
      elevation in EDLF and altered membrane components do not play a role in the down
      regulation of Na(+)-K+ ATPase. Therefore other factors (presence of other
      inhibitors and/or reduced number of enzyme molecules) should contribute to the
      lower activity of the Na(+)-K+ pump.

PMID- 8863872
TI  - Circulating noradrenaline and beta-adrenergic receptors in children with
      congestive heart failure.
AB  - This study was designed to investigate changes in plasma catecholamine
      concentrations and the number of beta-adrenoceptors (beta-AR) of circulating
      lymphocyte in 94 noncyanotic congenital heart patients. In 43 patients with
      congestive heart failure, beta-AR density was significantly lower (p < 0.001) and
      plasma noradrenergic levels were significantly higher (p < 0.001) compared with
      corresponding values in 51 patients without heart failure. A significant negative
      correlation between lymphocyte beta-AR density and plasma noradrenergic levels
      was observed (r = -0.61, p < 0.001). The degree of left-to-right shunt and
      pulmonary pressure was correlated directly with noradrenaline level and inversely
      with lymphocyte beta-AR density. Both plasma noradrenaline level and lymphocyte
      beta-AR density return to normal in children with heart failure after surgical
      repair. Our results support the idea that changes in noradrenaline level and
      lymphocyte beta-adrenoceptor density occur concurrently with the presence and
      severity of heart failure in children.

PMID- 8863873
TI  - The natural history of cardiac rhabdomyoma with and without tuberous sclerosis.
AB  - The aim of the present study is to contribute to the knowledge of the natural
      history of cardiac rhabdomyoma in children with and without tuberous sclerosis.
      In a retrospective study, 33 children with cardiac rhabdomyoma were collected
      from three pediatric cardiology centres. In 30/33 patients tuberous sclerosis was
      associated. High prevalence of cardiac rhabdomyoma was found in infancy, with
      21/23 detected before the age of 1 year, and 11/33 before 1 month of age. Cardiac
      manifestations were present in 19 patients: cardiac rhythm disturbances were
      detected in 13; in 6/33 a Wolff-Parkinson-White syndrome was documented, of which
      4 presented paroxysmal arrhythmias. Obstructive or regurgitative phenomena were
      present in 5; and in 2 patients surgical removal proved necessary. With the
      exception of one tumoural mass in the right atrium, all 77 tumours were located
      somewhere in the ventricles, including at atrio-ventricular valve level. Because
      of spontaneous regression of most of the tumoural masses, treatment should at
      first be symptomatic, while surgical removal is required only in life-threatening
      conditions, as documented in 2 of our 33 patients.

PMID- 8863874
TI  - Chronic diarrhoea as a dominating symptom in two children with cerebrotendinous
      xanthomatosis.
AB  - The objective of this study was to describe diarrhoea as a dominating symptom of
      cerebrotendinous xanthomatosis (CTX), a lipid storage disease, and investigate
      its cause. Two children with chronic diarrhoea as the dominating symptom of CTX
      are presented. Before and after therapy with orally administered chenodeoxycholic
      acid (15 mg kg-1 24 h, in three divided doses) bile alcohol excretion in urine,
      serum cholestanol level, serum bile acid patterns and faecal bile acids were
      measured. All routine gastro-intestinal investigations before therapy were
      normal. Diarrhoea ceased immediately after starting treatment with
      chenodeoxycholic acid. Abnormal bile alcohol excretion in urine decreased rapidly
      during the first days and elevated serum cholestanol level normalized in 2 years.
      We postulate the presence of bile alcohols in the lumen of the gut as most likely
      cause for diarrhoea in CTX, since the rapid decrease of bile alcohol excretion is
      associated with prompt cessation of diarrhoea after starting treatment with
      chenodeoxycholic acid.

PMID- 8863875
TI  - Clinical and biochemical screening for Smith-Lemli-Opitz syndrome. Italian SLOS
      Collaborative Group.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomalies/mental
      retardation disorder possibly due to a defect of delta 7-sterol reductase,
      leading to low plasma cholesterol levels and to the accumulation of 7
      dehydrocholesterol (7-DHC) and other cholesterol precursors. This study aimed to
      identify clinical features that could potentially be specific indicators for the
      clinical diagnosis of SLOS, and to test the reliability of ultraviolet
      spectrophotometry (UVS) as a biochemical screening procedure for the syndrome.
      Twenty patients with clinical suspicion of SLOS, referred to 11 Italian
      paediatric and clinical genetic centres, were collected during 1994. In 10
      patients the diagnosis was confirmed biochemically by gas chromatography/mass
      spectrometry (GC/MS) analysis of serum sterols, whereas in the other 10 patients
      the serum sterol profiles were normal. A comparison between confirmed SLOS
      patients and biochemically negative subjects did not show clinical signs specific
      for the syndrome. UVS measurement of 7-DHC correlated well with GC/MS profiles,
      showing 100% sensitivity and specificity. Four out of five patients had serum
      bile acid concentrations below the normal range of controls.

PMID- 8863876
TI  - Maternal hyperphenylalaninaemia as a cause of microcephaly and mental
      retardation.
AB  - We attempted to evaluate the role of maternal hyperphenylalaninaemia (HPA) as an
      isolated cause of mental retardation and microcephaly in children. This
      transversal study observed the plasma phenylalanine from mothers of 161 children
      with mental retardation and/or microcephaly of unknown origin. In this sample, we
      found two women with previously undiagnosed HPA, a frequency (2/161) higher than
      expected for our general population (1:12 500) (p < 0.001). We concluded that the
      plasma phenylalanine levels should be determined during preconceptional
      evaluation of every woman of reproductive age that already has had a child
      affected either by mental retardation or microcephaly of unknown cause. It is
      particularly significant where women currently having their pregnancies have not
      been screened for phenylketonuria as newborns, as happens in most developing
      countries.

PMID- 8863877
TI  - Psychological reactions at the onset of insulin-dependent diabetes mellitus in
      children and later adjustment and metabolic control.
AB  - The initial psychological reactions at the onset of insulin-dependent diabetes
      mellitus (IDDM) in a population-based sample of 76 children were studied with
      staff observations and a self-report questionnaire for children 12 years of age
      and more. Younger children reacted with more anger and less distress than the
      older children. High initial self-reported distress was associated with poorer
      subjective psychological IDDM adjustment at a follow-up 10 months later for the
      older children. The children's initial reactions as well as later adjustment were
      intimately associated with maternal initial reactions in the total group. The
      metabolic control, estimated as the mean level of the major fraction of
      glycosylated haemoglobin (Hb AIc) during the first 2 years, was poorer in the
      adolescent group. Initial anxiety over injections and protest but low general
      distress in mothers and children were associated with better metabolic control.

PMID- 8863878
TI  - The changing panorama of cerebral palsy in Sweden. VII. Prevalence and origin in
      the birth year period 1987-90.
AB  - This seventh Swedish population-based cerebral palsy (CP) report comprises 216
      children born between 1987 and 1990. The crude live birth prevalence was 2.36 per
      1000, indicating a break in the continuous increase since 1970. Excluding 10
      postnatally-derived cases, gestational-age specific prevalences were 80 for
      extremely, 54 for very and 8 for moderately preterms and 1.4 for term children
      per 1000. Birth weight-specific prevalences were 57 for birth weights < 1000 g,
      68 for 1000-1499 g, 14 for 1500-2499 g and 1.4 for > or = 2500 g per 1000. The
      aetiology was considered prenatal in 8%, peri/neonatal in 54% and unclassifiable
      in 38% of preterms and 33, 28 and 39% of term children. Hemiplegic, diplegic and
      tetraplegic syndromes accounted for 22, 66 and 7% of preterms and 44, 29 and 10%
      of term children. Non-walking, mental retardation, epilepsy, severe visual
      impairment and infantile hydrocephalus were present in 39, 39, 26, 18 and 23% of
      preterms; and 38, 44, 36, 14 and 5% of term children, respectively. The entire
      series of 1408 cases born in 1954-90 revealed three distinct trend eras for
      preterms, clearly related to changes in perinatal care and shifts in type of CP
      manifestations.

PMID- 8863879
TI  - Recurrent abdominal pain and Helicobacter pylori in a community-based sample of
      London children.
AB  - Helicobacter pylori is accepted as an important factor in the pathogenesis of
      peptic ulcer disease. Infection is probably most commonly acquired in early life
      but there is still limited information on the prevalence or symptomatology of H.
      pylori infection in childhood. The aim of the present study was to establish the
      prevalence of H. pylori infection in a large sample of urban school children and
      to determine its relationship, if any, to a history of recurrent abdominal pain.
      Using a commercial ELISA significant levels of anti-H. pylori IgG antibody were
      detected in 107/640 (16.7%) of school children (M, 383; F, 257; mean age 9.15
      years, range 4-13). No relationship was demonstrated between H. pylori
      seropositivity and a personal or family history of recurrent abdominal pain or
      the nature of the pain.

PMID- 8863880
TI  - Asthma and atopy in schoolchildren in a defined population.
AB  - We investigated the frequency of allergic disorders, the pattern of allergen
      sensitization and serum total IgE concentration in a population-based sample of
      schoolchildren screened on the basis of respiratory symptoms (N = 244). The
      children were classified on clinical grounds into three groups, asthma (N = 43),
      other symptoms from lower airways (OSLA; N = 34) and control children (N = 167).
      The frequency of allergic disorders (allergic rhinitis, conjunctivitis or
      dermatitis) differed significantly between children with asthma (81%), children
      with OSLA (62%) and in control children (48%) (p < 0.001). The presence of at
      least one positive skin prick test result was equally common in children with
      asthma or OSLA (77%), but lower in control children (40%) (p < 0.001). Serum
      total IgE concentrations did not differ between the three groups. Two conclusions
      can be drawn: (i) there is a strong association between clinical allergy, skin
      reactivity and asthma in school age children, and (ii) a similar association is
      present between allergy and asthma-like conditions.

PMID- 8863882
TI  - An assessment of behavioural characteristics in infants who died of sudden infant
      death syndrome using the Early Infancy Temperament Questionnaire.
AB  - An assessment of the behavioural peculiarities of infants dying of sudden infant
      death syndrome (SIDS) was carried out using the Early Infancy Temperament
      Questionnaire (EITQ). Thirty-six infants (25 boys and 11 girls aged 1-4 months)
      in whom the diagnosis of SIDS was confirmed by full necropsy and who died in St
      Petersburg from 1990 to 1992 entered the study, and the families were approached
      contemporaneously. A control group consisted of an equal number of age, sex,
      geographic distribution and date of birth matched live infants from the same
      city. The infants who died of SIDS had significantly lower estimates of activity
      in comparison with the babies from the control group. Behavioural defects may be
      a contributory factor and a sign of increased risk in some babies presenting with
      SIDS.

PMID- 8863881
TI  - Serum vitamin A in relation to socio-economic, demographic and dietary
      characteristics in Bangladeshi children.
AB  - The purpose of this study was to examine socio-economic conditions, demographic
      factors, use of vitamin A capsules and dietary practices in relation to the risk
      of low serum vitamin A. One hundred and twenty four night blind cases were
      identified by parents in a cross-sectional survey in Bangladesh in 1992. Age-,
      sex- and neighbourhood-matched controls were selected. Venous blood was collected
      from 87 cases and 97 controls for the determination of serum vitamin A.
      Information about socio-economic conditions, demographic factors, use of vitamin
      A capsules and dietary practices was obtained by interview. The level of serum
      vitamin A was strongly related to age and consumption of beta-carotene rich
      foods. The preschool years (2-6 years) are important risk periods for vitamin A
      deficiency among children. We conclude that long-term prevention of vitamin A
      deficiency should rely on efforts to improve local diet.

PMID- 8863883
TI  - Survival of orphans in 19th century Sweden--the importance of remarriages.
AB  - The study aims at elucidating the fate of orphans in 19th century Sweden. A
      cohort of all children born in the region of Sundsvall was followed. The Cox
      regression model was used. The population increased 12-fold in the sawmill
      parish, and doubled in the other parishes. Every 13th child lost either his or
      her mother or father. The death risk represented by being a motherless infant
      exceeded every other death risk for the child, and was further enhanced if
      parents were crofters or coming from the sawmill parish. For children beyond the
      age of 1 year, factors other than parental deprivation became decisive. Step
      parents had an immense positive influence on the survival of the children. The
      social network worked relatively well for those children who were orphans beyond
      the age of 1 year. The motherless infants had the worst outcome. The best chance
      for survival was found for children with step-parents.

PMID- 8863884
TI  - Transcutaneous bilirubinometry in Chinese, Malay and Indian infants.
AB  - The objective of this study was to investigate the correlation of transcutaneous
      bilirubinometry (TcB) and plasma bilirubin concentrations in full-term Chinese,
      Malay and Indian infants. TcB was performed with the Minolta Airshields
      bilirubinometer on Chinese, Malay and Indian fullterm infants. The readings were
      taken on the chest (sternum) and forehead (glabella) when capillary blood was
      sampled for bilirubin determination. Five hundred and forty TcB indices in 253
      Chinese infants, 282 in 169 Malay infants, and 182 in 120 Indian infants were
      obtained over the sternum and forehead. A good correlation between the TcB
      indices and the bilirubin concentrations was observed in Chinese, Malay and
      Indian infants: r = 0.78 (chest), r = 0.73 (forehead); r = 0.86 (chest), r = 0.84
      (forehead); and r = 0.84 (chest), r = 0.82 (forehead). The correlation was just
      as good when the combined values were evaluated together: r = 0.80 (chest) r =
      0.75 (forehead). In Chinese infants, correlation at values below 250 mumol l-1
      was significantly better than that at values over 250 mumol l-1 r = 0.80 versus r
      = -0.20, p < 0.00001 (chest), and r = 0.74 versus r = 0.07, p < 0.00001
      (forehead). However, a safer cut-off point clinically would be 200 mumol l-1,
      since only relatively few higher bilirubin values were encountered when TcB
      indices were below 200 mumol l-1. The same pattern was noticed with the other two
      groups, and the combined group. Thus, TcB provides a non-invasive, cost-effective
      screening method for significant neonatal jaundice, sparing infants and parents
      physical and emotional stress, and medical and nursing personnel extra work and
      inconvenience.

PMID- 8863885
TI  - Chlamydia trachomatis-associated respiratory disease in the very early neonatal
      period.
AB  - Of 103 preterm neonates admitted consecutively to the neonatal intensive care
      unit soon after birth for respiratory distress, 8 were found to be Chlamydia
      trachomatis-positive as early as within the first 24 h of life. All these
      patients required mechanical ventilation and supplemental oxygen. Six infants had
      evidence on chest radiographs of hyaline membrane disease, one of pneumonia, and
      one of slight bilateral parenchymal changes. Our results suggest that the
      presence of C. trachomatis in preterm infants with neonatal respiratory distress
      is probably not an infrequent event.

PMID- 8863886
TI  - Epidemiology of infant Kawasaki disease with a report of the youngest neonatal
      case ever reported in Japan.
AB  - Our objectives were to describe epidemiological pictures of infant Kawasaki
      disease (KD) and to report the youngest patient ever reported in Japan. A
      Japanese database of 105755 KD patients reported in the 25 year period since 1970
      was analyzed. Of all the cases registered, there were only six cases aged 30 days
      or younger and 1768 cases (1.67%) aged 90 days or younger. We reported a typical
      case of KD (female, the onset at 20 days old) who was the youngest patient ever
      reported in Japan. The epidemiology of KD in early infants does not contradict
      the infection theory of the etiology; the rare incidence in the neonatal period
      can be explained by the protective effects of the passive immunity transferred
      from the mother and by exposure to the unknown infectious agents.

PMID- 8863888
TI  - Lipoid proteinosis in three children.
AB  - We report on three children with lipoid proteinosis, an autosomal recessive
      disorder characterized by the deposition of hyaline-like material in the skin,
      mucous membranes and other tissues. All cases had characteristic hoarseness.
      Other symptoms observed were infiltrated whitish plaques and pock-like scars on
      the face, papules on the palpebral margins, and infiltrates in the mucous
      membranes of the lower lip and tongue. Two of the children were siblings whose
      parents were first cousins.

PMID- 8863887
TI  - Restricted catch-up growth after cessation of steroid treatment in a growth
      hormone-deficient child.
AB  - The phenomenon of catch-up growth has been known for a long time but its actual
      stimulus has remained unidentified. Involvement of growth hormone (GH) seems
      likely, but it is unknown whether normal GH secretion is an absolute prerequisite
      for catch-up growth. We present insight to this topic by describing a child with
      GH deficiency who showed a biphasic pattern of catch-up growth. During the first
      catch-up phase, she showed restricted catch-up growth in the absence of GH
      therapy, while she achieved nearly complete catch-up with GH therapy. Both
      periods of catch-up growth are compared separately with the response to GH
      therapy of age-matched, GH deficient patients with similar height deficit. This
      observation suggests that the first phase of catch-up growth in a child with
      severe growth retardation may be partially GH independent, while further catch-up
      requires normal GH levels.

PMID- 8863889
TI  - A case of Guillain-Barre syndrome accompanied by sympathetic overactivity and
      hypertensive encephalopathy.
AB  - Hypertension has often been observed in patients with Guillain-Barre syndrome,
      and various underlying mechanisms have been implicated. We report the case of a
      child with the Guillain-Barre syndrome whose hypertension was associated with
      increases in both renin activity and circulating catecholamines. This case also
      appeared to be complicated by hypertensive encephalopathy. Following
      administration of intravenous regitine, a blood pressure change was observed and
      cardiac performance was assessed by two-dimensional echocardiography. Results
      indicated that increased total peripheral resistance may have been responsible
      for the symptoms and the hypertension. The hypertension was effectively managed
      by nifedipine, captopril and prazosin without the need for beta-blockade.

PMID- 8863890
TI  - Recurrent exercise-induced acute renal failure in renal hypouricemia.
AB  - We describe a male patient with four episodes of acute renal failure after
      strenuous exercise occurring between the age of 14 and 25 years. He was found to
      have low serum uric acid (0.4 mg dl-1 after recovery) and high fractional
      excretion of uric acid. A benzbromarone/pyrazinamide test suggested that renal
      hypouricemia was due to defective proximal tubular reabsorption of uric acid at a
      presecretory site. A renal biopsy revealed acute tubular necrosis, a renal
      computer tomography scan showed patchy contrast enhancement and a treadmill
      exercise test induced an immediate fall in creatinine clearance. These findings
      suggest that the cause of acute renal failure was renal vasoconstriction rather
      than obstruction by uric acid crystals.

PMID- 8863891
TI  - Transformation and recovery of rat skeletal muscles in pathologic hormonal
      states.
AB  - There are numerous controversial data published on muscle transformation in
      pathologic endocrine states. Information is consistent in respect of slow muscle
      sensitivity to diabetes, but data concerning characteristics of fast muscles are
      contradictory under the same conditions. Sensitivity of fast and slow muscles to
      diabetes was examined and compared in this study. Diabetes was induced by a
      single intravenous dose of Streptozotocin in Wistar rats. Contractile parameters
      of soleus and extensor digitorum longus muscle were determined by in vitro
      measurements. We collected data on reversibility of diabetic transformation using
      exogenous thyroxine and insulin treatment. Insulin was used both to prevent and
      revert diabetic transformations. We found that, according to the data previously
      published, soleus muscle is more sensitive to diabetes than the extensor
      digitorum longus (EDL). Changes in the EDL muscle proved not to be statistically
      significant, but the comparison of hyperthyroid and diabetic muscles to controls
      led us to the conclusion that there is a sublimital transformation in the EDL in
      diabetes. T4 and insulin were effective in preventing diabetic muscle
      transformation. Application of insulin not only prevented diabetic complications,
      but its use in animals suffering from diabetes for a longer time (8 weeks)
      resulted in a successful recovery of the muscle transformation.

PMID- 8863892
TI  - Characteristics of stretch-release induced tension development in arterial smooth
      muscle.
AB  - Stretching helical strips of porcine a. carotis comm. to 1.7 times the resting
      length increases myosin light chain phosphorylation from 0.22 to 0.67 mol
      phosphate/mol light chain. While stretch is maintained, the stretch induced light
      chain phosphorylation decreases and reaches the resting level over a period of 60
      minutes. The fully stretched arterial strips containing maximally phosphorylated
      myosin light chain cannot generate active tension which indicates, according to
      the sliding filament theory, the lack of overlap between actin and myosin
      filaments. When stretch is released from these muscle strips active tension
      develops. The amplitude of this stretch-release induced tension depends on the
      level of myosin light chain phosphorylation related to the time interval between
      stretch and release as well as on the extent of the overlap zone related to the
      length of the released strip. Three-dimensional graphic representation of both
      measured and interpolated data points in an active tension-light chain
      phosphorylation-muscle length space reveals a contractility surface which
      demonstrates that active tension appears as a sigmoidal function of light chain
      phosphorylation, on the one hand and shows maximum as a function of muscle
      length, on the other hand.

PMID- 8863894
TI  - Interference of sulphonylurea antidiabetica with mitochondrial bioenergetics
      under in vivo conditions.
AB  - Sulphonylurea antidiabetica effectively inhibits the basal hepatic glucose
      production. Since it has been firmly established that lipophylic sulphonylurea
      drugs exerted an uncoupling effect on mitochondrial oxidative phosphorylation, a
      relationship between the reduction of hepatic gluconeogenesis and the
      insufficient energy supply due to sulphonylureas could be supposed. In this study
      we have investigated the effects of glibenclamide and gliquidone on mitochondrial
      bioenergetics in liver after peroral treatments of normal rats with different
      doses. The treatment of rats with 5 mg/kg glibenclamide or gliquidone daily for
      14 days elicited only a marginal inhibition on mitochondrial oxidation capacity
      and remained without any effect on mitochondrial ATPase activity. Only the
      supermaximal dose 50 mg/kg for 14 day produced a significant damage in the
      mitochondrial functions. The basal respiration increased with 60-80 per cent,
      whereas the ADP- or DNP-stimulated oxygen consumption significantly decreased
      independently from the respiratory substrates investigated. Similar alterations
      were found in the mitochondrial ATPase activity after treatment with these drugs.
      No essential differences have been observed in the actions between glibenclamide
      and gliquidone. However, the lowest dose applied in this study is many times
      higher than the usual therapeutic dose. Consequently, glibenclamide and
      gliquidone do not interact with mitochondrial bioenergetic processes under
      therapeutic conditions. On the other hand, in different liver and kidney damages
      we have no sufficient knowledge whether these drugs can be accumulated in these
      organs and therefore their elevated concentration may interfere with the
      mitochondrial energy metabolism.

PMID- 8863893
TI  - Interference of the sulphonylurea antidiabeticum gliquidone with mitochondrial
      bioenergetics in the rat under in vitro conditions.
AB  - The hypoglycaemic sulphonylurea gliquidone and glibenclamide exerted a partial
      uncoupling effect on mitochondrial respiration of liver under in vitro conditions
      using various citrate cycle intermediates as substrates. Besides the uncoupling
      effect, gliquidone and glibenclamide caused a direct inhibition of ATP-as well as
      DNP-stimulated oxygen consumption. Both phenomena proved to be dose dependent.
      Respiratory control ratio decreased progressively with increasing concentrations
      of sulphonylureas mainly through the inhibition of ADP-stimulated respiration.
      Basal and DNP-stimulated ATP-ase activity of isolated mitochondria changed
      similarly to the respiratory parameters. Changes in membrane permeability of
      mitochondria and the inhibition of substrate uptake further support the
      assumption of structural and functional alteration of mitochondria by the
      hypoglycaemic compounds tested.

PMID- 8863895
TI  - Effect of streptozotocin-induced diabetes on kidney Na+/K(+)-ATPase.
AB  - The maximal capacity of low affinity ouabain binding sites in kidney medulla was
      found to be increased by 20 +/- 3.8% after 2 weeks, and by 35 +/- 4.5% in 4 weeks
      diabetes. However, in kidney cortex no similar changes could be detected. Western
      blot analysis of Na+/K(+)-ATPase subunits in kidney medulla indicated a
      significant enhancement of both the alpha 1 and beta 1 subunit in two and four
      weeks diabetic rats (alpha 1: 35 +/- 3.1, 51 +/- 5.8% and beta 1: 31.3 +/- 5.2
      and 43.2 +/- 6.8%, respectively). However, kidney cortex showed no significant
      change in any condition tested. In diabetes we could detect a significant change
      only in the medulla in case of the b subunit mRNA transcript, which showed 1.69
      +/- 0.59 and 2.89 +/- 0.81 times increased in two and four weeks diabetic state,
      respectively. There was no change in the alpha 1 subunit mRNA abundance. Insulin
      treatment of diabetic animals did not result in a complete reversal of diabetes
      induced changes in ouabain binding capacity or in the amount of Na+/K(+)-ATPase
      alpha 1 and beta 1 subunit protein and mRNA levels. Our data indicate a good
      correlation between changes in low affinity ouabain binding capacity and the
      level of alpha 1 isoform in diabetic rats, and suggest an important role of the b
      subunit in the regulation of enzyme quantity.

PMID- 8863896
TI  - Changes of the 78 kDa glucose-regulated protein (grp78) in livers of diabetic
      rats.
AB  - The 78 kDa glucose-regulated protein (grp78) is an abundant member of the 70 kDa
      molecular chaperone family in the lumen of the endoplasmic reticulum
      participating in the quality control of secretory proteins. In the present paper
      we have analysed the synthesis and level of grp78 in livers of control,
      streptozotocin-diabetic, and the spontaneously diabetic Zucker rats. The level of
      grp78 mRNA significantly decreased in streptozotocin-diabetic rats. The effect
      was reversed by insulin treatment. In case of Zucker rats we did not detect any
      significant change in grp78 mRNA, grp78 protein level showed opposite changes
      being essentially unchanged in streptozotocin-diabetes and significantly reduced
      in Zucker rats. Autoradiograms of Ca-dependent phosphorylation of
      postmitochondrial supernatants of control and streptozotocin-diabetic livers
      indicated no significant changes in the 70 kDa region. Decrease in the
      availability of grp78 may participate in the attenuation of hepatic protein
      secretion in diabetes.

PMID- 8863897
TI  - Effect of irradiation on the GTP binding kinetics of chicken embryo brain plasma
      membranes.
AB  - The membrane bound form of the catalytic subunit of adenylate cyclase of chicken
      embryo brain has been found earlier to be rather radioresistant [28]. The
      radiation induced changes of G proteins of membrane preparations of 19 day old
      chicken embryo brains were investigated in this work. The activation of catalytic
      subunit of adenylate cyclase by G protein dependent activators (Gpp/NH/p and NaF)
      was found elevated at lower radiation doses (0-400 Gy), while both basal enzyme
      activity (measured without any activator) and the activity measured in the
      presence of activators decreased at higher doses (above 800 Gy). Heterogeneity of
      GTP binding sites measured with 3-H-Gpp/NH/p a GTP-ase resistant GTP analogue was
      observed in the case of control (with Kd1 = 0.0663 +/- 0.034 mumol/l, Bmax =
      0.0079 +/- 0.0022 nmol/ml and Kd2 = 2.038 +/- 0.4779 mumol/l, Bmax2 = 0.0291 +/-
      0.0017 nmol/ml). The lower affinity high capacity binding sites seemed to be more
      radiosensitive, than the higher affinity sites. A marked decrease was observed in
      the number of low affinity binding sites above 200 Gy and these low affinity
      binding sites practically disappeared after irradiation with 400 Gy. At high
      doses (above 1600 Gy) the catalytic subunit was damaged, too. On the basis of the
      decrease of low affinity binding sites together with an increase in activation of
      the catalytic subunit via G proteins one can conclude that it is caused by
      radiation induced damage of Gi protein that can be more radiosensitive, than Gs
      protein.

PMID- 8863898
TI  - Intestinal elimination of p-nitrophenol in the rat.
AB  - The intestinal metabolism and metabolite transport of p-nitrophenol (PNP), as a
      model compound have been investigated in an in vivo isolated intestinal loop
      preparation in the rat. Different PNP concentrations (20 microM, 100 microM and
      500 microM) were recirculated to determine the formation and transport of PNP
      metabolites (PNP-glucuronide: PNP-G and PNP-sulphate: PNP-S) in the jejunal loop.
      It was found that the jejunum of the rat was able to metabolize PNP rapidly and
      to transport the metabolites efficiently back into the luminal solution. About
      21, 16 and 6% of recirculated amount of PNP could be detected in 90 minutes as
      PNP-G in the lumen of jejunal loop when 20, 100 or 500 microM PNP was perfused.
      These results show that the luminal appearance of PNP-G tended to saturability.
      Sulphate conjugate of PNP was undetectable in the intestinal lumen at 20 and 100
      microM PNP concentrations and PNP-S amounted to 0.07% of recirculated amount of
      PNP when it was used in a concentrations of 500 microM. These results indicate
      that the intestinal metabolism and the excretion of metabolites may play a role
      in the elimination of xenobiotics containing phenolic hydroxyl groups and that
      the small intestine of the rat forms predominantly PNP-G after luminal
      administration of PNP.

PMID- 8863899
TI  - Effect of hyperglycaemia on the hepatic metabolism and excretion of xenobiotics.
AB  - The biliary excretion of drugs has been investigated in hyperglycaemic male
      Wistar rats. Hyperglycaemia was produced by a continuous infusion of glucose in
      different concentrations. To examine the effect of hyperglycaemia on the biliary
      excretion rate of xenobiotics, one representative of non-metabolizing exogenous
      organic anions (rose bengal) and metabolizing phenolic drugs (p-nitrophenol) as
      model compounds were used. A dose-dependent increase of blood and bile glucose
      level was found after the continuous infusion of glucose in a concentration of
      10, 20 or 30%. Biliary flow and biliary excretion of rose bengal were
      significantly depressed in hyperglycaemic rats. Hepatic conjugation of p
      nitrophenol with glucuronic acid appeared to be decreased, however, a
      compensatory increase of sulphoconjugation of p-nitrophenol was observed in
      hyperglycaemic rats. Biliary excretion of unconjugated p-nitrophenol was
      negatively influenced by high blood glucose level and the overall hepatic
      elimination of p-nitrophenol was also diminished by hyperglycaemia. Insulin (I
      U/kg i.v.) compensated partly the depressive effect of high blood sugar level on
      the biliary excretion rate of rose bengal, however, it was unable to abolish
      completely the negative effects of hyperglycaemia. These results indicate that
      hyperglycaemia does alter the hepatic elimination of xenobiotics.

PMID- 8863900
TI  - Segmental flexibility of cardiac myosins.
AB  - Conventional and saturation transfer electron paramagnetic resonance spectroscopy
      (EPR and ST EPR) and differential scanning calorimetry (DSC) were used to study
      the motional dynamics and structural stability of cardiac myosins. Cardiac
      myosins isolated from bovine and human heart muscle were spin-labelled with a
      maleimide- or an iodoacetamide-based probe molecule at the reactive sulhydryl
      sites (Cys-697 and Cys-707). The probe molecules rotated with an effective
      rotational correlation time of 0.04 microsecond which was at least six times
      shorter than the rotational correlation time of the same label on skeletal
      myosin. In the presence of MgADP, flexibility changes in the multisubunit
      structure of myosins were detected, but this did not lead to changes of the
      overall rotational property of the myosin heads. Temperature dependence of the
      EPR spectra of maleimide spin-labelled myosin showed continuous decrease of the
      spectral parameters (amplitude ratio of the diagnostic peak heights in the ST EPR
      time domain and hyperfine splitting constant) at increasing temperature. In
      contrast, marked changes were obtained at about 17 degrees C in light chain-2
      deficient myosin. DSC measurements supported the view that the removal of the
      light chain-2 produced additional loosening in the multisubunit structure of
      cardiac myosin. It is postulated that the light chain-2 is an integral part of
      myosin, and there is an intersite communication between light chain-2 and the 20
      kDa subunit.

PMID- 8863901
TI  - Effect of radioprotectors on the aggregability, cAMP and thiol content of blood
      platelets.
AB  - Aminothiol radioprotectors (MEA, AET, WR-1065) were found to be inhibitors of
      platelet aggregation. The aim of this study has been to clarify the potential
      involvement of the adenylate cyclase-cAMP system in this effect. In vitro
      aminothiol compounds (> 1 mmol/l) inhibited platelet function as well as AC
      activity, i.e. significantly reduced their cAMP content. In less than 1 mmol/l
      concentration WR-1065 elevated the cAMP content of PGI2-stimulated platelets,
      while basal cAMP level mainly remained unchanged. On the effect of WR-1065 the
      level of non-protein thiols (NP-SH) markedly elevated in the platelets, while
      their protein-bound thiol content (PB-SH) either decreased or remained at control
      level. The phosphorothioate WR-2721 was effective only after in vitro or in vivo
      dephosphorylation. Although the amount of NP-SH slightly increased, the PB-SH
      content decreased in the platelets isolated after intravenous administration of
      WR-2721. Moreover, platelet-poor plasma samples of WR-2721 treated animals also
      inhibited both the AC-activity and function of control platelets, too. Based on
      these results it is suggested that aminothiol radioprotectors non-specifically
      inhibit platelet functions forming mixed disulfides with endogenous, mostly
      protein-bound thiols. The slight elevation of AC-activity caused by low doses of
      WR-1065 also suggest that the AC-complex consists of unevenly sensitive subunits
      (G-proteins, catalytic subunit).

PMID- 8863902
TI  - Intrarenal distribution of renal blood flow after acute and chronic
      administration of nitric oxide-synthase inhibitor.
AB  - The effects of acute and chronic inhibition of endothelium derived relaxing
      factor (EDRF/NO) synthesis were investigated on the intrarenal blood flow in
      anaesthetized rats. N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) was
      used for inhibition of NO-synthase. In acute experiments L-NAME was infused,
      while in chronic experiments L-NAME (4-day pretreatment) was dissolved in the
      drinking water. Blood flow was measured by 86-Rubidium accumulation method. Renal
      blood flow decreased markedly after both acute and chronic L-NAME treatment.
      (Acute: RBF-control: 679 +/- 122, RBF-L-NAME: 333 +/- 65 ml/min/100 g, p < 0.01;
      Chronic: RBF-control: 527 +/- 133, RBF-L-NAME: 315 +/- 75 ml/min/100 g, p <
      0.01). The consequences of the NO-synthase blockade are different in the cortical
      and medullary vessels. The increase in the vascular resistance in the medulla (in
      acute experiments 228%, R-control: 2.76 +/- 0.76, R-L-NAME: 9.08 +/- 4.36 R, p <
      0.01; in chronic experiments 113%, R-control: 3.89 +/- 1.20, R-NAME: 8.31 +/-
      3.75 R, p < 0.01) is appreciably greater than in the cortex (acute blockade:
      112%, R-control: 1.12 +/- 0.29, R-L-NAME: 2.38 +/- 0.47 R, p < 0.01; chronic
      blockade: 62%, R-control: 1.61 +/- 1.03, R-L-NAME: 2.61 +/- 0.61 R, p < 0.01).
      The percentile distribution of intrarenal blood flow shifts from the medulla
      toward the cortex following acute NO-synthase blockade (MBF-control: 16.8 +/-
      1.11%; MBF-NAME: 12.3 +/- 2.66%, p < 0.01). The proportion of cortical and
      medullary blood flow remains unaltered after chronic NO-synthase inhibition.
      CONCLUSION: The nitric oxide plays an important role in determining the renal,
      cortical and medullary blood flow. The effect of EDRF in influencing the vascular
      resistance is more pronounced in the medulla than in the cortex.

PMID- 8863903
TI  - 100,000 quinacrine sterilizations.
AB  - 100000 quinacrine nonsurgical female sterilizations have been completed over the
      past decade involving transcervical insertion of quinacrine (252 mg) as pellets
      by one, two or three monthly insertions. No deaths have been reported and serious
      complications are far fewer than for surgical sterilization. Side-effects are
      mild and transient. Efficacy has improved from 3 pregnancy failures per 100 women
      at one year to approximately 1 by improved insertion technique and use of
      adjuvants. Long-term follow-up of early cases in Chile shows no increased risk of
      cancer for this method. The main advantage of quinacrine sterilization is its
      ability to raise contraceptive prevalence and thereby reduce maternal mortality
      and morbidity, especially in rural and urban slum areas of developing countries.
      It should be made available as an option to well informed women everywhere as an
      economical and safe permanent family planning method.

PMID- 8863904
TI  - Is tubal sterilization associated with an increased risk of subsequent
      hysterectomy but a decreased risk of ovarian cancer? A review of recent
      literature.
AB  - Recent epidemiologic studies have suggested that tubal sterilization (TS) may
      lead to an increased incidence of subsequent hysterectomy but a decreased risk of
      ovarian cancer. This review evaluates the nature and magnitude of these two
      relationships, which should be of great concern and interest to women, clinicians
      and the administrators of family planning programs. The positive relationship
      between TS and subsequent hysterectomy is more likely to be of a motivational
      rather than biological nature, and a considerable number of unnecessary
      hysterectomies after TS could be avoided by changing the attitudes of physicians
      and women. The inverse relationship between TS and ovarian cancer appears causal,
      although the exact biological mechanisms remain to be clarified. Theoretically,
      this non-contraceptive beneficial effect of TS could be used as a primary
      preventive measure to curb the incidence of the highly fatal ovarian cancer.
      However, a number of medical, ethical, and economic questions attending use of a
      generally irreversible contraceptive procedure as a preventive measure must first
      be answered. The issue of whether TS is associated with any long-term sequelae,
      and, if so, whether the association is of a cause-and-effect nature or a by
      product of time passage and aging of the woman, should be addressed by well
      designed studies.

PMID- 8863906
TI  - The CUE Fertility Monitor compared to ultrasound and LH peak measurements for
      fertile time ovulation detection.
AB  - A prospective study of the reliability of the CUE Fertility Monitor to identify
      the fertile time of the menstrual cycle was conducted. The device provides a
      digital measurement of the electrical resistance of saliva (SER) and vaginal
      secretions (VL). The readings of the device were compared with the fertile time
      detected by ultrasonography of the growing follicle and estimation of the LH
      surge to detect ovulation. Thirteen women participated in the study. Sixteen
      cycles contained both signals (SER, VL) for the beginning and the end of the
      fertile period. In 2 cycles a CUE signal could not be found by the device. Using
      a computerized algorithm for evaluation of the CUE signals, the beginning of the
      fertile period was accurately detected in 14 cycles; in 2 cycles the signal was
      found less than five days prior to ovulation. The last day of fertility was
      identified correctly by the CUE Fertility Monitor in 10 cycles; in 6 it was
      incorrectly identified during the time when the woman was still fertile. This
      suggests that the CUE Fertility Monitor utilizing the algorithm on which it
      currently is based cannot be recommended for natural family planning. However, we
      think that the algorithm for evaluation should be improved as useful signals in
      the menstrual cycle are detected.

PMID- 8863905
TI  - Risk for ovulation in women taking a low-dose oral contraceptive (Microgynon)
      when receiving antibacterial treatment with a fluoroquinolone (ofloxacin).
AB  - The possibility of escape ovulation in women using a fluoroquinolone ofloxacin
      for antibacterial treatment at a dose of 200 mg twice daily for 7 days when
      taking a combined oral contraceptive (Microgynon, 150 micrograms levonorgestrel
      and 30 micrograms ethinyl estradiol) was studied in 20 women. By using a placebo
      controlled, randomized, cross-over design 6 contraceptive pill cycles were
      followed. Follicle-stimulating hormone and estradiol concentrations were measured
      on tablet days 5-8, 19-21; progesterone was assayed on days 19-21 during
      treatment with ofloxacin or placebo. Ultrasonographical investigations for
      measurements of the number and diameter of ovarian follicles were performed on
      one of days 5-10, 11-17, 18-24, 25-28. No indications of ovulation during
      ofloxacin medication were detected. It is concluded that alternative
      contraceptive precautions should not be needed when ofloxacin is prescribed for
      patients taking oral contraceptives.

PMID- 8863907
TI  - Calendar rhythm efficacy: a review.
AB  - OBJECTIVE: To estimate the unplanned pregnancy rate of calendar rhythm. DESIGN:
      Meta-analysis of eight studies of calendar rhythm published between 1940 and
      1989. RESULTS: There exist few studies of the calendar rhythm method. Analysis of
      the best of these studies resulted in a conservative estimated Pearl rate of 18.5
      +/- 1.8, and a less conservative estimate of 15.0 +/- 4.0, standardized to 12
      months' observation; these results are in the range of other natural and barrier
      methods. DISCUSSION: We need properly done clinical trials of the calendar rhythm
      method to scientifically establish its effectiveness.

PMID- 8863908
TI  - The fiction of an ideal hormonal contraceptive.

PMID- 8863909
TI  - Oral misoprostol use in early complicated pregnancy.
AB  - Eighty-four patients with early complicated pregnancies such as intrauterine
      death, blighted ovum pregnancy and missed abortion were treated with oral
      misoprostol. If abortion did not occur, 200 micrograms misoprostol was given once
      an hour, with an average dose of 1000 micrograms (min 200 micrograms, max 1200
      micrograms). Complete or partial abortion took place within 7.0 +/- 5.1 h in
      92.5% of patients. Of the patients, 11.9% and 83.3% had complete and partial
      abortion, respectively, without major complications. We observed only minor side
      effects such as nausea, vomiting, diarrhea, hypotension, fever, headache and
      abdominal pain. This study demonstrates that the use of oral misoprostol is a
      simple, inexpensive and easy procedure for terminating early complicated
      pregnancies, although additional surgical evacuation of the uterus was required
      in the large majority of patients.

PMID- 8863910
TI  - Chlamydia trachomatis detected in cervical smears from Copper-T users by DFA
      test.
AB  - OBJECTIVE: This study was carried out to determine the prevalence of Chlamydia
      trachomatis (CT) antigen in endocervical smears from women using the Copper-T200
      (Cu-T) intrauterine device and comparing them with nonusers. METHODS: The direct
      fluorescent antibody (DFA) test was used to detect the CT antigen (CT Ag).
      RESULTS: A total of 422 women between 17 and 42 years of age was evaluated. Out
      of these 71 (16.8%) were positive for CT Ag. Among Cu-T users (n = 222), 14.0%
      were positive. The duration of Cu-T use varied from 6 to 80 months. Among
      nonusers (n = 200), the DFA test was positive in 20.0% (p = 0.11, NS). However,
      as a whole, symptoms related to genital tract infection were significantly more
      common in Copper-T users than in nonusers (p < 0.02) and signs were relatively
      more common in Cu-T users but not significantly so (p = 0.16). Similarly, as a
      group, symptoms as well as signs were significantly more common in all DFA
      positive cases than in all negative cases (p < 0.02). Among Cu-T users, symptoms
      were relatively more common, and signs were significantly more common, in women
      positive for CT Ag than in the negative cases (p < 0.04). There were two cases of
      mild pelvic inflammatory disease (PID) diagnosed clinically, one in a Copper-T
      user, and the other a nonuser, both being positive by the DFA test. CONCLUSION:
      There was no correlation between the duration of Copper-T use and percent
      positivity for CT Ag. Although milder genital tract symptoms and signs were more
      common in women with chlamydial cervicitis, clinically PID appears to be uncommon
      (0.5%). PID in this study was not related to Copper-T use but related to
      chlamydial cervicitis in this group of women with low risk sexual behavior.

PMID- 8863911
TI  - Supporting children in need through a community-based orphan visiting programme.
AB  - There is an urgent need for programmes to be established to support the growing
      number of orphans in countries severely affected by AIDS. Most orphans are being
      cared for by extended families under difficult circumstances. Few descriptions of
      community-based orphan support programmes exist. We describe one such programme
      established in Zimbabwe in 1993. Twenty-five volunteers identified 300 orphan
      households. During one year, volunteers made 1725 home visits and 123 households
      received an average of $11 in material support or school fees. In 292 orphan
      households there were 702 orphans, 14.7% of children under 15 years in the area.
      The rate of parental deaths was increasing with 3.5% of households in the area
      having a parental death in 1994. Forty-five per cent of caregivers were
      grandparents and 33% of caregivers were over 60 years. Three per cent of orphans
      were cared for by adolescent siblings. The poorest orphan households were those
      in receipt of school fees, with out-of-school children or with an older sibling
      as caregiver. Community members initiated activities to help orphans. The
      programme described is targeted, effective and replicable. Community-based
      organizations such as local churches and women's groups can be mobilized to
      administer programmes which provide support to the poorest orphan households.

PMID- 8863912
TI  - Patrons of the sex industry: perceptions of risk.
AB  - This paper reports on an in-depth study of how men who buy sex construe risk in
      relation to their sexual activities. Twenty men were contacted in a massage
      parlour, four more through sex workers or newspaper advertisements. In-depth,
      face-to-face interviews were recorded. Two main discourses were articulated by
      the men to "manage' risk. Parlour clients articulated a discourse of the "cordon
      sanitaire' which they defined in various way to encompass elements of both
      commercial and non-commercial sex. Most felt while they operated within this they
      ran only those risks inevitable in life. Outside the cordon were dangerous
      venues, especially the streets. A few felt either fatalistic or invulnerable
      about possibilities of risk even within this "cordon sanitaire'. Street clients
      articulated a different discourse about risk, based on a strategy of
      discrimination between women.

PMID- 8863913
TI  - Segmentation of heterosexual prostitution into various forms: a barrier to the
      potential transmission of HIV.
AB  - The results of an earlier Dutch study on prostitutes' clients, interviewed face
      to-face, were cross-validated by means of telephone interviews, which both
      guaranteed anonymity and produced a larger sample of respondents (n = 559).
      Depending on their preference and financial resources, they had visited different
      types of prostitution; but about half of them had restricted themselves to one
      type. Inconsistent use of condoms was reported by 14% of the clients who had had
      vaginal or anal intercourse. Condoms were most frequently used in clubs, brothels
      and window prostitution, and least often in street, home and escort prostitution;
      in the last two sorts especially not with regular prostitutes. Whether or not
      prostitutes came from non-Western countries had no influence on protective
      behaviour of these clients. The formation of networks between different sorts of
      prostitution, through unsafe sexual contacts in two or more sorts, involved only
      3% of respondents. Thus, prostitution in The Netherlands should be seen as a
      number of sparsely-connected networks rather than as a single network. The
      formation of networks between prostitution and the population at large is made
      possible by the 10% of the respondents who had had unsafe contacts with both
      commercial and private partners.

PMID- 8863914
TI  - Depression and use of mental health services among HIV-infected men.
AB  - Depression is a serious, common, and treatable condition among HIV-infected
      persons. We examined the prevalence and predictors of depression and use of
      mental health services among 475 HIV-infected men without AIDS. Participants were
      drawn from three sites in San Francisco and Denver that did not provide ongoing
      medical care or mental health services. Depression was measured using the Center
      for Epidemiology Studies Depression scale (CES-D). Overall, 176 men (37.1%) were
      classified as depressed based on having a CES-D score above the standard cut-off
      of > or = 16. In logistic regression analysis, persons with HIV-related symptoms
      (OR = 3.4; 95% CI = 2.0.-5.6), low social support (OR = 2.5; 95% CI = 1.6-3.9),
      who were unemployed (OR = 1.9; 95% CI = 1.1-3.3), and with CD4 count < 200 cells
      (OR = 1.9; 95% CI = 1.1-3.3), were significantly more likely to be depressed.
      Only 40.3% of depressed men had seen a mental health clinician in the previous
      year and only 6.3% were taking an antidepressant. Among depressed men, in
      logistic regression analysis, men who were unemployed (OR = 2.4; 95% CI = 1.2
      4.7) and those with health insurance (OR = 2.2; 95% CI = 1.1-4.5) were more
      likely to have received these services. Increased evaluation and treatment of HIV
      infected persons for depression is needed.

PMID- 8863915
TI  - Sexual debut and predictors of condom use among secondary school students in
      Arusha, Tanzania.
AB  - A cross-sectional survey was conducted using interviews among 852 students
      attending seven secondary schools in the Arusha region, Northern Tanzania, to
      predict determinants of sexual debut and recent condom use among students.
      Schools were sampled according to location, school size and ownership criteria.
      Subjects were randomly sampled within grade-level and gender through use of class
      registers. Altogether, 528 students were sexually active. Males were more likely
      than females to report their sexual debut status (82.0% versus 33.3%; OR = 8.78;
      95% CI: 6.17-12.49). Among males, incidence of sexual debut increased with grade
      level, but decreased according to religious affiliation. None of the socio
      demographic predictor variables used in this study had a significant association
      with sexual debut among females when age was controlled for. Of the sexually
      active students, 26.8% reported having ever used a condom and 21.5% reported use
      of condoms during their most recent sexual encounter. Late sexual debut,
      prolonged duration of dating before intercourse and having only one sex partner
      were significantly associated with increased condom use during the most recent
      occasion. Condom use increased with levels of education, but gender was not
      significantly linked to increased condom use. Condom use was particularly
      infrequent among casual sex partners. We observed a marked gender difference
      among students with respect to their sexual debut status, but no such difference
      was found in relation to condom use.

PMID- 8863916
TI  - College students' perceptions of the prevalence of risky sexual behaviour.
AB  - In contrast to previous research which has largely focused on students'
      perceptions of other students' risk for contracting HIV/STDs, this study assessed
      single heterosexual college students' (96 men, 121 women) perceptions of the
      prevalence of different sexual behaviours which increase a person's risk for
      HIV/STD infection (e.g. multiple sexual partners, unprotected sexual intercourse,
      one-time sexual encounters). Consistent with previous research which has
      demonstrated an overestimation bias in judging others' risk for HIV/STD
      infection, students' estimates about the prevalence of sexual behaviours
      increasing a person's risk for HIV/STD infection were similarly overestimated
      relative to reported base rates. Gender differences were also observed. Although
      women generally tended to give higher prevalence estimates than men, overall,
      participants gave higher estimates when judging the behaviour of men compared to
      women. Both motivational and cognitive explanations of our data are discussed.
      Our findings highlight the importance of developing sexual risk reduction
      programmes which (a) enable students to make more accurate personal risk
      judgements, (b) increase students' awareness of the riskiness of their own sexual
      behaviours, and (c) promote positive health changes (e.g. increased condom use)
      in normative sexual behaviour among college students.

PMID- 8863917
TI  - Community service needs of people with HIV infection in London.
AB  - The objectives of this study were to describe the expressed needs for community
      services of HIV-infected individuals by disease stage, gender and transmission
      category and the barriers which prevent the receipt of such services. Structured
      interviewer-administered questionnaires concerning a 6-month retrospective period
      were used to obtain information on need for community services and problems which
      prevented the receipt of services. The study sample included 70 homosexual men
      with asymptomatic HIV disease, 42 homosexual men with symptomatic non-AIDS, 53
      homosexual men with AIDS, 23 heterosexual men, 29 heterosexual women, 9 male and
      9 female injecting drug users. The main outcome measures were the extent to which
      needs for community services were met and person/service combinations for which
      problems or barriers prevented the receipt of community services. On average,
      subjects expressed a need for 10 categories of community services over the 6
      month period: homosexuals expressed a mean of 10, heterosexuals 10, injecting
      drug users 11, subjects with asymptomatic HIV infection 9, subjects with
      symptomatic non-AIDS 11, subjects with AIDS 13, men 9 and women 14. A total of
      58% of community service needs were always met, 6% were rarely not met, 16% were
      sometimes not met, 6% were often not met and 14% were not met at all. The extent
      to which subjects felt that their needs were met was similar for the different
      study groups, but the needs of women were met somewhat less frequently than those
      of men. Similarly, people with AIDS felt that their needs were met slightly less
      often. Reported levels of unmet need were high for a wide range of services. The
      most common reason subjects gave for not having received a community service for
      which they expressed a need was ignorance of where or how to obtain the service.
      This was mentioned in one-third of all such cases. Anxieties over the competence
      with which a service would be rendered was mentioned in 13% of cases and long
      waiting times in 11%. The frequencies of unmet need for many community services
      were high and often seemed to arise either from a lack of awareness on the part
      of subjects on how and where services could be obtained or from doubts about the
      relevance of services offered. Both of these barriers should be surmountable
      through the provision of better information to patients, extending user
      involvement in service development and the better co-ordination of service
      delivery through care management approaches.

PMID- 8863918
TI  - Nurses' intentions to provide home care: the impact of AIDS and homosexuality.
AB  - The purpose of this experimental study was to identify key factors influencing
      the intention of nurses (n = 102) to provide care at home to AIDS or leukaemia
      patients, homosexual or heterosexual. Ajzen's theory of planned behaviour with
      the addition of personal normative belief borrowed from Triandis's theory defined
      the theoretical framework. Homophobia and social desirability were also assessed
      as control variables. All nurses completed a self-administered and anonymous
      questionnaire after reading one of the four randomly-assigned vignettes that
      described the context of care. Sexual orientation of the patient influenced the
      personal normative belief (p < 0.05), and type of disease affected significantly
      perceived subjective social norm (p < 0.05). The regression of intention on all
      variables yielded an adjusted R2 of 0.48 (p < 0.0001), with perceived behavioural
      control, personal normative belief, attitude and homophobia being the significant
      predictors. In conclusion, nurses need to be better informed, better prepared and
      have better skills in order to provide appropriate care to homosexual AIDS
      patients.

PMID- 8863919
TI  - A primary health care service for Glasgow street sex workers--6 years experience
      of the "drop-in centre', 1989-1994.
AB  - In Glasgow, a health and social care centre opened in 1988 principally to
      facilitate HIV prevention among street prostitutes, most of whom are injecting
      drug users. During 1992 to 1994, 551 women made 17,554 visits to the medical room
      which is functional 5 nights per week. The mean age of the sex workers was 26
      years (range 15 to 62) and 89% injected drugs. Fifty-five per cent of the
      attendances were for needle/syringe exchange only whilst the remainder involved
      other health care provision. Common presenting problems included abscesses, burns
      and venous thromboses, reflecting the high proportion of sex workers who injected
      drugs. Most women always used condoms for penetrative commercial sex and
      symptomatic sexually transmitted disease was seen infrequently. In addition to
      the provision of injecting equipment and condoms, other key prevention activities
      included Hepatitis B vaccination and cervical screening. The prevalence of HIV
      infection amongst the women remains under 5% and most seropositives were known to
      be infected before the Centre opened. This initiative shows that if
      multidisciplinary health and social services are provided to street sex workers
      at a time and place convenient to their work, the benefits are considerable.

PMID- 8863920
TI  - WHO global AIDS statistics.

PMID- 8863921
TI  - Maternofetal interaction and allergy.

PMID- 8863922
TI  - Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is
      increased in healthy-appearing skin.
AB  - In the skin of normal and atopic individuals, the expression of E-selectin (ELAM
      1), L-selectin (LECAM-1), P-selectin (CD62), CD31 (PECAM), vascular cell adhesion
      molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and cutaneous
      lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which
      were taken from normal individuals (n = 17), the healthy-appearing skin of
      patients with atopic dermatitis (n = 10), and their acute (n = 5) and chronic (n
      = 6) skin lesions. In contrast to ELAM-1, the expression of VCAM-1 and ICAM-1 was
      found to be significantly increased in nonlesional atopic skin in comparison to
      the skin of normal individuals. Moreover, in contrast to normal skin of healthy
      individuals, nonlesional atopic skin showed a further increase of VCAM-1, ICAM-1,
      and ELAM-1 when cultured with medium alone. This suggests that certain adhesion
      molecules are constitutively upregulated in healthy-appearing skin of patients
      with atopic dermatitis. In addition, atopic skin appears to respond to
      nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM
      1, ICAM-1, and ELAM-1. It is suggested that the observed upregulation of adhesion
      molecules is mediated by the release of cytokines such as interleukin-4 from
      cells which reside in atopic skin. The question of whether the inherent
      upregulation of adhesion molecules in atopic skin contributes to the development
      of Th2 cells, which have been found to predominate in atopic inflammation, has to
      be further investigated.

PMID- 8863923
TI  - Skin prick tests and specific IgE in adults from three different areas of Sweden.
AB  - The aims of this part of the European Respiratory Health Survey were to estimate
      the prevalence of atopic sensitization to inhalant allergens among adults in
      three different areas of Sweden and to investigate the association between
      sensitization and certain risk factors. Randomly selected subjects aged 20-46
      years from Goteborg, Uppsala, and Vasterbotten were investigated with the skin
      prick test (SPT), analyses for specific IgE antibodies in serum (specific IgE)
      and total serum immunoglobulin E (total IgE), and a questionnaire. SPT was
      performed in 1572 subjects and analyses of specific IgE in 1470. One or more
      positive SPT were found in 35.6% and one or more positive specific IgE in 31.7%
      approximately the same values in all three areas. Birch, grass, cat, and dog were
      the most frequent sensitizing agents and occurred at similar prevalences, i.e.,
      around 15%, in all areas. The SPT to mite was positive in 14.1% in Goteborg, 7.4%
      in Uppsala, and 7.9% in Vasterbotten. A positive SPT to pellitory of the wall
      (Parietaria), not described previously in Sweden, was found in 3.4% in Goteborg.
      Living in Goteborg was independently associated with a higher risk of a positive
      SPT to mite and Parietaria. Heredity, male sex, and low age were independently
      associated with atopy. Birth in the Scandinavian countries was independently
      associated with sensitization to cat, whereas birth in other countries was
      associated with sensitization to mite. The overall prevalence of atopy was
      similar in the three Swedish areas, but the sensitizing allergens varied. There
      is an indication that sensitization is increasing in the population, as low age
      was associated with sensitization. Sensitization to cat, but not to mite, appears
      to be particularly important in persons born in the Scandinavian countries.

PMID- 8863924
TI  - Isotypic analysis of grass-pollen-specific antibodies in human plasma. III.
      Relationship to autoantibodies to IgE.
AB  - Since it has been shown that autoanti-IgE may be mistaken for antiallergen
      antibodies, thus appearing as pseudo-allergen-specific antibodies, it is crucial
      to separate true-from pseudo-allergen-specific antibodies and to determine to
      what extent autoanti-IgE appeared as pseudo-allergen-specific antibodies. For
      this purpose, human Ig pools were affinity-purified successively on a grass
      pollen column and then on an antihuman-IgE column. IgG1-4, IgA, and IgM
      antibodies that were eluted from the grass-pollen column separated into pseudo-
      (approximately 30-40%) and true-allergen-specific antibodies that were coretained
      and not coretained, respectively, with the IgE on the anti-IgE column. Levels of
      autoanti-IgE were determined in individual plasma samples by surface plasmon
      resonance and statistically compared to the concentrations of allergen-specific
      antibodies obtained previously in the same plasma samples. A positive correlation
      between IgM autoanti-IgE levels and grass-pollen- "specific" IgM concentrations
      (P < 0.0002), and negative correlations between IgA autoanti-IgE and both IgE
      anti-grass pollen and IgG2 autoanti-IgE levels (P < 0.03, in both cases) were
      observed for the first time. This supports the contentions that: (1) autoanti-IgE
      antibodies appeared as pseudo-grass-pollen-specific antibodies, (2) they hid IgE
      antibodies when the latter were measured, and (3) they compete with one another
      in binding IgE. Lastly, a model of large Ig complexes is discussed.

PMID- 8863925
TI  - Eosinophil activity markers in peripheral blood have high predictive value for
      bronchial hyperreactivity in patients with suspected mild asthma.
AB  - The present study aimed to evaluate the predictive value of eosinophils and
      markers of their activity for bronchial hyperreactivity (BHR) in a population of
      patients with recently developed clinical symptoms of asthma. The activation of
      eosinophils was estimated by measuring eosinophil cationic protein (ECP) in
      serum. In addition, flow cytometry was used to measure the expression of the EG2
      epitope on intracellular ECP in eosinophils from peripheral blood. Twenty-eight
      consecutive patients with clinical history of asthma were studied. Of the 28
      patients, 18 had a positive bronchial challenge test measured as PD20 < or = 1600
      micrograms histamine. A significantly higher concentration of eosinophils and a
      trend to higher ECP in the peripheral blood was found in the hyperreactive group
      than in the nonreactive group. However, the intracellular expression of ECP did
      not correlate with the PD20 value, and no significant difference between the
      groups was found. With one eosinophil activity marker, either serum ECP or EG2,
      BHR could be predicted in 70% of the patients. If we combined any two of the
      activity markers (serum ECP, EG2, or the percentage of eosinophils), the
      predictive value increased to 100%. We conclude that the blood eosinophil
      concentration, as well as, to some extent, serum ECP, has a high specificity for
      BHR in patients with recently developed clinical symptoms of asthma. Despite
      normal bronchial reactivity, some patients had signs of activated eosinophils,
      i.e., high serum ECP and increased EG2 expression. Thus, these markers may
      reflect early stages in the development of BHR. Our results also indicate that a
      combined evaluation of percentage of eosinophils and of eosinophil activity
      markers is of clinical value to predict BHR.

PMID- 8863926
TI  - A double-blind, placebo-controlled study of immunotherapy with grass-pollen
      extract Alutard SQ during a 3-year period with initial rush immunotherapy.
AB  - Thirty patients with asthma and/or monosensitized allergic rhinitis caused by
      grass pollen whose ages ranged from 15 to 35 years were selected. Two groups were
      established at random: an active group and a placebo group, and a double-blind
      study was done on treatment with immunotherapy for a period of 3 continuous
      years, with initiation doses administered according to the rush immunotherapy
      technique. Grass-pollen allergen extract Alutard SQ and histamine as a placebo
      were used. The objective parameters of efficacy evaluated were end-point
      cutaneous tests, conjunctival provocation, bronchial provocation, and
      symptom/medication scores, as well as specific immunoglobulin determinations. The
      statistical evaluation of the results was significant for the differences
      existing between the initial and final time of the active group, and there were
      significant differences between the two groups for all of the parameters
      considered. We found no relationship between clinical improvement and the range
      of specific immunoglobulin E values. Regarding the safety of the treatment,
      systemic adverse effects were manifested only in the initial phase (rush
      immunotherapy), and were easily controlled by treatment. We conclude that the
      efficacy and safety of immunotherapy with grass pollen make it possible to
      consider this treatment fundamental in these patients.

PMID- 8863927
TI  - Sensitization to Dermatophagoides siboney, Blomia tropicalis, and other domestic
      mites in asthmatic patients.
AB  - Mite species adapted to warm, humid climates are commonly found in house dust in
      the tropics. In Cuba, Dermatophagoides pteronyssinus, D. siboney, and Blomia
      tropicalis are the most common and abundant mite species in house dust. To
      investigate the pattern of sensitization of Cuban asthmatic patients to common
      mite species, we skin-prick-tested (SPT) 148 patients with a clinical history of
      asthma and possible mite allergy, and determined specific IgE antibodies against
      mite allergens (D. pteronyssinus, D. farinae, D. siboney, B. tropicalis, Acarus
      siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, and Glycyphagus
      domesticus). The prevalence of positive SPT was high to D. siboney (88%), D.
      pteronyssinus (87%), A. siro (85%), B. tropicalis (85%), and D. farinae (83%).
      The largest skin reactions were obtained with D. siboney and B. tropicalis
      extracts. The skin test response to the D. siboney extract correlated to those of
      D. farinae, D. pteronyssinus, B. tropicalis, and A. siro. The highest IgE levels
      were found to Dermatophagoides species and B. tropicalis. IgE to D. siboney and
      B. tropicalis were found in 97% and 96% of the patients, respectively. The
      prevalence of specific IgE to the other mites studied varied from 46 to 65%. D.
      siboney and B. tropicalis are important sensitizers among asthmatic patients in
      Cuba.

PMID- 8863928
TI  - Increased in vitro cysteinyl leukotriene release from blood leukocytes in
      patients with asthma, nasal polyps, and aspirin intolerance.
AB  - In vitro cysteinyl leukotriene (cLT) release from blood leukocytes was measured
      in eight normal individuals (NI), nine patients with nasal polyps (NP) without
      aspirin intolerance, and eight patients with NP, asthma, and aspirin intolerance
      (AI). Blood leukocytes were prestimulated with interleukin-3 (IL-3) and incubated
      with acetylsalicylic acid (ASA) (10 and 100 micrograms/ml) together with C5a (10(
      8) mol/l) for 18 h. cLT release (LTC4, LTD4 and LTE4) from blood leukocytes was
      measured with a competitive enzyme-linked immunoassay. Background cLT release was
      259 +/- 66 pg/ml (mean +/- SEM) in the NI group, 185 +/- 33 pg/ml in the NP
      group, and 578 +/- 136 pg/ml in the AI group (P = 0.1). After incubation with 10
      micrograms/ml ASA, cLT concentration was lower in normal subjects (346 +/- 72
      pg/ml) and in patients with NP (209 +/- 53) than in patients with AI (686 +/- 75
      pg/ml, P = 0.002). After incubation with 100 micrograms/ml ASA, cLT
      concentrations were 285 +/- 72 pg/ml in the NI group, 313 +/- 77 pg/ml in the NP
      group, and 654 +/- 121 pg/ml in the AI group (P = 0.04), respectively.
      Simultaneous incubation with ASA 10 micrograms/ml and C5a (10(-8)mol/l) resulted
      in a cLT concentration of 751 +/- 171 pg/ml in the NI group, 343 +/- 102 pg/ml in
      the NP group, and 2196 +/- 480 pg/ml in patients with AI (P = 0.0006), whereas
      simultaneous incubation with ASA 100 g/ml and C5a (10(-8)mol/l) resulted in 268
      +/- 51 pg/ml in the NI group, 412 +/- 97 pg/ml in the NP group, and 1701 +/- 368
      pg/ml in the AI group (P = 0.005). In patients with AI, cLT release from blood
      leukocytes is altered when compared with normals and patients with NP. The
      presented cLT-release assay could be of potential use in the in vitro diagnosis
      of AI.

PMID- 8863930
TI  - Adverse reaction to bupivacaine.

PMID- 8863929
TI  - Transient sensitization to house-dust mites: a study on the influence of mite
      exposure and sex.
AB  - This study aimed to evaluate the prognosis of a previous positive skin test to
      house-dust mites (HDM) in relation to environmental exposure. A total of 115
      children, 50 from Stockholm and 65 from northern Sweden, all with a previous
      (average 2.5 years) positive Phazet (Pharmacia AB, Uppsala, Sweden) skin prick
      test (SPT) to extracts of Dermatophagoides pteronyssinus (Dpt) and/or D. farinae
      (Df) were included. Dust samples were collected from the children's mattresses,
      and the total (Dpt, Df, and D. microceras [Dm]) amount of major mite allergen was
      measured by ELISA (50 children) and expressed as microgram allergen per gram of
      dust, or was measured by microscopy (65 children). The results of microscopic
      mite counts were transformed to approximate allergen levels as 2 micrograms
      equals 100 mites per gram of dust. Of 115 originally SPT-positive children, only
      48 (48%) remained positive at retest, while the majority (58%) were SPT negative
      after 2 years. Among the 67 converted children, 11 were still exposed to mite
      allergen, but only to low concentrations (only one converted child being exposed
      above the suggested threshold level [TLV] of 2 micrograms/g), compared to 15/48
      children still SPT positive who were exposed above the TLV. This shows that
      continued mite exposure is a major risk factor (OR = 30, CI 4.8-184) for
      continued positive SPT to HDM. A minor risk factor for continued sensitization
      was sex, boys having a higher risk than girls (OR = 2.2, CI 1.0-4.8). In
      conclusion, a surprisingly high rate of SPT conversion occurred, mainly as a
      result of a favorable indoor environment with low exposure to HDM and, to a
      lesser degree, as a result of sex. The present results support the view that the
      risk level of exposure is 2 micrograms mite allergen per gram of dust.

PMID- 8863931
TI  - Intolerance to sodium metabisulfite in beer.

PMID- 8863932
TI  - Prevalence of allergic conjunctivitis in Italian young men.

PMID- 8863933
TI  - Presidential address--trends, tools, and technology.

PMID- 8863934
TI  - Legitimizing occupational therapy's knowledge.
AB  - Proceeding from the ethic that occupational therapy is the rightful keeper of its
      own practice and knowledge, this article strives to bring the profession's
      knowledge concerning the role of occupation in adaptation into sharp relief.
      Knowledge generated by many occupational therapists represented in the
      profession's historic literature, scholarship, practice models, position papers,
      and research is analyzed through a heuristic framework that distinguishes the
      process from the state of adaptation. This analysis offers evidence that, in the
      service of persons with profound and often medically incurable disabilities,
      occupational therapy has begun to explicate the role of occupation as a vital
      adaptive medium and cornerstone of quality in daily living. Related areas of
      knowledge development in which legitimate progress can be claimed are suggested.
      Nevertheless, it is argued that occupational therapy's knowledge must be further
      developed and its societal value better communicated through the concerted
      efforts of all practitioners, educators, and researchers.

PMID- 8863935
TI  - Moving occupation into treatment: clinical interpretation of "legitimizing
      occupational therapy's knowledge".

PMID- 8863936
TI  - The effects of an occupationally embedded exercise on bilaterally assisted
      supination in persons with hemiplegia.
AB  - OBJECTIVES: Occupationally embedded exercise is a central idea in the profession
      of occupational therapy. This experiment compared the effect of an occupationally
      embedded exercise involving a simple dice game with a rote exercise in persons
      with stroke with pronator spasticity. Both exercise conditions involved
      bilaterally assisted supination, consistent with the neurodevelopmental model of
      practice. METHODS: The sample consisted of 14 men and 12 women post
      cerebrovascular accident with a mean age of 68.4 years (SD = 11.2) at six
      clinical sites in California, Texas, and Michigan. Subjects had pronator
      spasticity, full passive range for supination after a brief warm-up, and no
      functional supination. After random assignment for experimental condition, the
      subjects engaged in two sets of 10 repetitions of bilaterally assisted supination
      in either the occupationally embedded condition (dice game) or the rote condition
      (no game). A pen recorder electronically documented degrees of rotation of the
      handle that was grasped during the exercise. RESULTS: The occupationally embedded
      exercise resulted in significantly more handle rotation (requiring more
      supination) than the rote exercise, t (24) = 2.28, p (one tailed) < .05. The
      effect size was large. CONCLUSION: This study advances the experimental analysis
      of therapeutic occupation in the area of occupationally embedded exercise.
      Clinicians are urged to consider the multidimensional nature of occupationally
      embedded exercise.

PMID- 8863937
TI  - An analysis of score patterns of children with attention disorders on the Sensory
      Integration and Praxis Tests.
AB  - OBJECTIVES: The purpose of this study was to identify and describe the score
      patterns of children with attention deficit hyperactivity disorder (ADHD) on the
      Sensory Integration and Praxis Tests (SIPT) and to determine whether their score
      patterns differ significantly from those of children without ADHD. METHOD: In
      this retrospective study, the score patterns of 309 children with ADHD were
      compared with a group of 309 children without ADHD. The children were matched by
      norm group (reflecting age), gender, and the presence or absence of a learning
      disability. Both descriptive statistics and multivariate techniques were used.
      RESULTS: Subjects with ADHD demonstrated relative strengths in the areas of
      nonmotor visual perception and localization of tactile input and weaknesses with
      vestibular processing and in most areas of praxis or motor planning. Certain SIPT
      scores of subjects with ADHD were found to differ significantly from those of
      subjects without ADHD. The SIPT test that best discriminated the two groups was
      Space Visualization. CONCLUSIONS: The results suggest that it may be helpful for
      therapists to consider the areas of praxis and vestibular processing in the
      evaluation and treatment of children with ADHD and that in clinical practice, it
      would be difficult to distinguish children with ADHD from those without on the
      basis of their SIPT scores. However, the ways in which the SIPT score patterns of
      children with ADHD differed from those without assist our understanding of the
      brain areas and neurological systems involved in children with ADHD.

PMID- 8863938
TI  - Art: an occupation with promise for developing empathy.
AB  - Empathy is central to the interactions of occupational therapists who value
      personal dignity. Persons from various sectors of the behavioral sciences and the
      medical humanities have proposed that engagement with the arts can develop
      empathy, an assumption that prompted this inquiry. The observations of artists
      and art philosophers suggest that the assumption that art may develop empathy is
      grounded in the kindred natures of the two practices and in the actions that
      occur when a person engages with a work of art. The assumption that art may
      develop empathy is grounded in the kinship of the actions common to both
      practices: response, emotion, and connection. Artists and art philosophers'
      observations of human practices have uncovered three rules of art that may
      dispose one toward empathy: reliance on bodily senses, use of metaphor, and
      occupation by virtual worlds. Analysis of art's potential suggests that a person
      who would derive empathy from art must (a) use the senses to grasp feeling, (b)
      stretch the imagination to see a new perspective, and (c) invite an occupation
      that enhances understanding. Persons who hope to develop empathy must pursue an
      experience that evokes the fellow feeling that inspires it. Art can offer this
      experience.

PMID- 8863939
TI  - Theory application by school-based occupational therapists.
AB  - OBJECTIVES: Recent literature indicates that there is an inconsistent use of
      theory to guide clinical actions by occupational therapists, including those
      working in pediatrics. The purpose of this study was to describe school-based
      therapists' theory application by collecting information about what frames of
      reference they used and why. METHOD: Of the 72 school-based therapists in the mid
      Atlantic states who agreed to respond to a questionnaire, 51 (70.8%) returned the
      questionnaire. Information about demographics, what frames of reference were
      used, and why they were used was obtained from the questionnaire. RESULTS:
      Respondents reported using a multitheoretical approach, with sensory integration
      theory and neurodevelopmental theory being the predominate frames of reference
      applied but not the only ones used. The frames of reference were used on the
      basis of several factors, including the children's needs and the respondent's
      education. CONCLUSION: Formal and continuing education seems to have a great
      effect on school-based occupational therapists as they develop their personal
      conceptual frameworks.

PMID- 8863940
TI  - Analysis of the orthopedic content in an occupational therapy curriculum from a
      clinical reasoning perspective.
AB  - OBJECTIVES: Recent studies have suggested that occupational therapists working
      with adults with physical disabilities do not use narrative reasoning in practice
      as much as they use procedural reasoning. This focus on procedural reasoning may
      be partially shaped by the occupational therapy educational process. The purpose
      of this analysis was to see whether one accredited occupational therapy
      curriculum was promoting narrative reasoning relative to its information on adult
      orthopedics. METHOD: An accredited occupational therapy undergraduate and
      certificate curriculum was analyzed from both student and faculty perspectives to
      see what types of clinical reasoning were most emphasized relative to treatment
      of adults with orthopedic injuries. The student analysis, done by a senior as
      part of an independent study, looked at the clinical reasoning content of journal
      articles, an occupational therapy textbook, and occupational therapy lectures
      relative to adult orthopedic injuries. The faculty analysis, part of a curriculum
      revision process and independent of the student analysis, looked at the clinical
      reasoning content of all courses in the curriculum. RESULTS: The student and
      faculty analyses concurred that although narrative reasoning is taught in this
      curriculum, narrative reasoning concepts are not well integrated into the adult
      physical dysfunction course that deals with adult orthopedic injuries.
      CONCLUSION: Occupational therapy educators may not be integrating narrative
      reasoning into more procedurally oriented physical dysfunction courses as fully
      as possible and may, therefore, be fostering procedurally oriented practice in
      physical dysfunction settings. Curricula evaluations, like the one described in
      this article, can be a mechanism for examining the types of clinical reasoning
      emphasized in a given curriculum for a given diagnostic group.

PMID- 8863941
TI  - Teaching strategies for the development of clinical reasoning.
AB  - A primary aim of occupational therapy education is to teach students how to think
      like practitioners, that is, how to engage in clinical reasoning. Since the early
      1980s, occupational therapy clinical reasoning research has elucidated a language
      that describes the various types of thinking therapists use in clinical practice,
      a language that has the potential to make previously tacit thought processes
      accessible to conscious examination and improvement. Occupational therapy
      educators can use that language to make their teaching of clinical reasoning more
      explicit to students. This article examines occupational therapy teaching methods
      using the language of clinical reasoning, categorizing them by the types of
      clinical reasoning they promote. Current clinical reasoning language is reviewed,
      and teaching strategies to facilitate the various types of clinical reasoning are
      described.

PMID- 8863942
TI  - Cruise ship accommodations for passengers with physical limitations due to
      disability or age.

PMID- 8863943
TI  - Chromosomal abnormalities: how much can we predict by ultrasound examination in
      low-risk pregnancies?
AB  - We examined the rates of chromosomal anomalies detected by ultrasound
      investigations for the whole region of Vienna. We evaluated the data of 250
      private offices, 10 clinics for Obstetrics and Gynecology, and one university
      Department of Prenatal Diagnosis and Therapy during the period from January,
      1990, to July, 1991. The study group consisted of low-risk patients, since cases
      where prenatal karyotyping has been performed for other reasons than sonographic
      findings (for example, maternal age) were excluded from the study. An overall
      detection rate of 53.7% was found for the region. Structural malformations of
      fetuses (41.5%) were the most prominent factors leading to the diagnosis of
      chromosomal abnormalities. In addition, detection rate of trisomy 21 (17.6%) by
      prenatal ultrasonography was found to be significantly lower compared to all
      other chromosomal abnormalities in our study (50 to 100%).

PMID- 8863944
TI  - Strategies for reducing the frequency of preeclampsia in pregnancies with insulin
      dependent diabetes mellitus.
AB  - The object of this study was whether improving glycemic control and maintaining
      normal glycosylated hemoglobin (HbA1c) through pregnancy can reduce the frequency
      of preeclampsia. One hundred and twenty-three complete medical records of
      pregnant insulin-dependent diabetics (IDDM) managed at Yale-New Haven Hospital
      from 1983 to 1993 were reviewed. Serial HbA1c measurements and the occurrence of
      preeclampsia were recorded. Based on the change of HbA1c values through the
      pregnancy, glycemic control was categorized into four groups: group 1, high to
      normal; group 2, high to high; group 3, normal to normal; group 4, normal to
      high. The association between HbA1c change and the incidence of preeclampsia was
      analyzed by chi-square test and Fisher's exact test. Among 123 IDDM pregnancies,
      40 (32.5%) developed preeclampsia. High HbA1c levels at any time in IDDM
      pregnancies were associated with an increased incidence of preeclampsia (group 1
      or 2 or 4 versus group 3). Reducing HbA1c by improving glycemic control both
      before and during pregnancy resulted in a significantly lower incidence of pre
      eclampsia (group 3 versus groups 1+2+4, p < 0.05). The best strategy for reducing
      the frequency of preeclampsia in IDDM pregnancies is by improving glycemic
      control before pregnancy.

PMID- 8863945
TI  - Changing epidemiology of triplet pregnancy: etiology and outcome over twelve
      years.
AB  - Neonates of 34 triplet pregnancies were admitted to our neonatal unit over a
      twelve-year period (1983 to 1995), with an incidence of 1 out of 812 deliveries.
      Thirty (88%) of the pregnancies were the result of ovulation induction and
      artificial fertilization: artificial insemination from husband (n = 3), in vitro
      fertilization (n = 9), and gamete intra-fallopian transfer (n = 6). All except
      one had antenatal sonographic diagnosis, 79% in the first trimester. The most
      common pregnancy-related complication was preterm labor (56%). Twenty-seven (79%)
      were delivered by cesarean section. There were 101 live births (one stillborn).
      Mean gestation age was 33.6 +/- 2.94 weeks, mean birthweight 1809 +/- 485 g, with
      7 extremely low birthweight (< 1000 g [6.8%]). Neonatal complications included
      respiratory distress syndrome (12%), intraventricular hemorrhage (8.8%),
      retinopathy of prematurity (8%), sepsis (3%), severe asphyxia (3%), and
      omphalopagus conjoined twins (1%). The perinatal and neonatal mortality was 49
      per 1000 and 59 per 1000, respectively. The introduction of advanced artificial
      fertilization techniques and ovulation induction agents resulted in a major
      increase in multifetal gestations. Early prenatal diagnosis, judicious
      prolongation of gestation, and planned delivery by cesarean section combined with
      major improvement in neonatal care by experienced neonatologists has improved
      survival of triplet neonates.

PMID- 8863946
TI  - Clinical defense response to cold and noise in preterm neonates after
      intrauterine conditions associated with chronic stress.
AB  - Threatening stimuli may trigger abnormal reaction patterns in animals and
      infants. We investigated whether chronic intrauterine stress influenced these
      reactions. The autonomic defense response to cold and noise in 21 preterm
      newborns who had suffered from chronic intrauterine stress, such as maternal
      smoking, maternal hypertension, and intrauterine growth retardation (STR-group)
      was compared with the response in 30 preterm newborns without such condition (C
      group). An ice cube was applied to the forehead and a 90 dB bleeptone was
      presented to the ears. After the cold test the heart rate, systolic, diastolic,
      and mean blood pressure increased in both groups, but to a lesser extent in the
      STR-group: the heart rate increased more at 2 minutes in the C-group (p = 0.009),
      and the systolic blood pressure was higher in the C-group at 30 seconds (p =
      0.007). The respiratory rate decreased in both groups. After the auditory
      stimulus, no significant difference in response between the two groups was seen
      for any of the parameters. The number of arousals between the two groups was
      similar for both tests; they uniformly resulted in increased heart and
      respiratory rates. The classic passive defense response was not observed in
      either group of preterm newborns. The observed reaction could be defined as a
      combination of a sympathetic, active fight-or-flight reaction and a
      parasympathetic passive freezing, or paralysis, reaction. The latter was less
      pronounced in the C-group. This may point to a change in the maturation of the
      autonomic nervous system after chronic intrauterine stress. It is speculated that
      this could make these infants more vulnerable in stressful situations.

PMID- 8863947
TI  - Serum vitamin A, vitamin E, and beta-carotene levels in preeclamptic women in
      northern nigeria.
AB  - We compared the serum levels of beta-carotene, vitamin A (retinol), and vitamin E
      (alpha-tocopherol) in healthy pregnant women and their counterparts who exhibited
      the signs and symptoms of preeclampsia or eclampsia, including: systolic blood
      pressure greater than 160 mm Hg, edema, and proteinuria. The study was conducted
      in the cities of Maiduguri and Bauchi, which are located in the semi-arid
      northeastern region of Nigeria. Most of the pregnant subjects: (1) were
      teenagers, though they ranged in age from 14 to 25 years; (2) had 2 or fewer
      prior pregnancies; and (3) were predominantly of the Muslim faith and members of
      the Hausa, Fulani, or Kanuri ethnic groups. Few of the women had received
      prenatal care. Serum levels of vitamins A and E and betacarotene were quantified
      using high pressure liquid chromatography. The serum vitamin A levels of the 9
      preeclamptic women (15.3 mg/dL) and the 7 eclamptic women (8.3 mg/dL) were
      significantly reduced (p < 0.01) relative to the serum vitamin A levels of
      healthy women in the third trimester (24.2 mg/dL). For the healthy pregnant
      controls, the levels of vitamins A and E and beta-carotene were relatively
      constant throughout pregnancy. The mean serum beta-carotene levels for both the
      preeclamptic and eclamptic groups of subjects were half as high as those of
      healthy control women in the third trimester (p = 0.004). The serum vitamin E
      levels of the preeclamptic and eclamptic women were 15% and 30% lower,
      respectively, than those of the corresponding controls (p < 0.01). The serum
      levels of these three lipids in the healthy pregnant and non-pregnant women we
      studied are similar to values reported by others for North American and European
      women of childbearing age. These results support the hypothesis that preeclampsia
      eclampsia deplete natural lipid antioxidants and suggest that the reduced levels
      of vitamin A in such women experiencing hypertension of pregnancy, if they happen
      to be infected with the HIV-1 virus, may place them at increased risk for mother
      child transmission of the virus.

PMID- 8863948
TI  - Induction of labor at 38 to 39 weeks of gestation reduces the incidence of
      shoulder dystocia in gestational diabetic patients class A2.
AB  - The purpose of this study was to test the hypothesis that the incidence of
      shoulder dystocia could be reduced in insulin-requiring diabetic women by
      elective induction of labor at 38 to 39 weeks of gestation. A prospective study
      protocol in which labor was induced at 38 to 39 weeks of gestation in insulin
      requiring diabetic women was executed between January 1, 1990, and July 31, 1994
      (n = 96). The outcome was compared to the results of a previous protocol (years
      1983 to 1989) in which the pregnancies were allowed to progress to spontaneous
      labor, unless fetal health became compromised (n = 164). The incidence of
      shoulder dystocia in patients in whom labor was electively induced at 38 to 39
      weeks of gestation was 1.4% as compared to 10.2% in patients who delivered beyond
      40 weeks' gestation (p < 0.05). No increase in cesarean section rate was
      demonstrated. We conclude that elective induction of labor is suggested for
      insulin-requiring diabetic women in order to reduce the incidence of shoulder
      dystocia.

PMID- 8863949
TI  - Blood gas profiles of fetuses with abnormal Doppler flow in the umbilical artery.
AB  - This study was designed to show how accurately the pulsed Doppler fetal blood
      flow velocimetry reflects fetal blood gas values. Abnormal Doppler umbilical
      artery (UA) velocimetry was defined when the value deviated from the 95%
      confidence interval of the normal fetuses. Fetal acidemia, hypoxemia, or
      hypercapnia was defined when the fetal blood gas taken by funipuncture during
      pregnancy deviated from the 95% confidence interval of the standard. Positive
      predictive values of abnormal UA Doppler with acidemia, hypoxemia, and
      hypercapnia were 26.3, 29.2, and 25.4%, respectively. When an absence or reversal
      of diastolic flow was observed, positive predictive values of absence or reversal
      of UA Doppler were 71.4 for acidemia, 71.4 for hypercapnia, and 71.4 for
      hypoxemia. In conclusion, although it is difficult to presume the fetal blood gas
      profile by Doppler velocimetry alone, we have to recognize the deterioration of
      the fetal blood gas profile when we observe the absence or reversal in diastolic
      flow in the UA.

PMID- 8863950
TI  - Hypoxemia associated with cimetidine therapy in a newborn infant.
AB  - Cimetidine therapy used for the treatment of gastric bleeding due to tolazoline
      therapy in a newborn infant was temporally associated with episodes of severe
      hypoxemia. It appears likely that the histamine H2 receptor blocked by cimetidine
      obviated the pulmonary vasodilator effect of tolazoline therapy.

PMID- 8863951
TI  - Spontaneous torticollis in a breech-presenting fetus delivered by an atraumatic
      elective cesarean section: a case and review of the literature.
AB  - A non-laboring patient with a breech-presenting fetus and oligohydramnios at 41
      weeks' gestation underwent elective cesarean delivery. The infant was delivered
      atraumatically through a wide transverse incision of the lower uterine segment.
      Severe leftsided torticollis was noted immediately at delivery. The torticollis
      subsequently responded to physiotherapy with minimal residual facial asymmetry.
      This case and the literature suggest that torticollis itself may predispose to
      breech presentation. Alternatively, in the case presented, oligohydramnios with
      subsequent restricted posture may have contributed to the underlying
      pathophysiology of this phenomena, which previously has been noted as associated
      with and as a possible sequela of traumatic vaginal breech delivery.

PMID- 8863953
TI  - Threshold value of glucose screening tests in pregnancy: could it be standardized
      for every population?
AB  - We aimed to determine a threshold value that perfectly demarcates women at high
      risk for gestational diabetes mellitus (GDM) in the Turkish population. One
      thousand gravid women of 24 to 32 weeks of gestation were given 50 g, 1-hour
      glucose screening tests. A 100 g, 3-hour glucose tolerance test (GTT) was
      performed on all patients whose screening test plasma glucose value was 130 mg/dL
      or greater. The sensitivity and specificity of each screening test value was
      found, and the GDM rate of each value was calculated. Three-hundred-and-five
      patients were identified for GTT and 66 were shown to have GDM with two or more
      abnormal values in GTT. The incidence of GDM was found to be 6.6%. The maximum
      specificity and sensitivity were met at 140 mg/dL. However, this value
      underestimated 12% of patients with GDM, and the lowest value for a positive GTT
      appeared to be 134 mg/dL. We recommend a 135 mg/dL threshold for GTT since this
      threshold accurately diagnoses almost all women with GDM while eliminating
      unnecessary GTT.

PMID- 8863952
TI  - Surfactant therapy prior to the interhospital transport of preterm infants.
AB  - The risk-to-benefit ratio of surfactant treatment of outborn preterm infants
      prior, as opposed to after, transportation to a perinatal center is not known.
      The objective of this study was to document current practice and to examine
      clinical outcomes in North America. In phase I (December, 1991 to January, 1992)
      questionnaires were distributed to 114 perinatal centers in the United States and
      Canada. The centers returned 98 surveys. Over half (50.5%) of the centers report
      giving surfactant rescue prior to infant transport, but only a minority (9.5%) of
      the centers report doing so for prophylaxis. In phase II (January, 1992 to
      December, 1992), clinical outcomes of surfactant-eligible babies requiring
      interhospital transport at a university hospital were evaluated to determine
      which infants ultimately received surfactant and when. The infants were compared
      between groups and did not differ significantly in gestational age, birthweight,
      sex type, number of multiple births, five-minute Apgar scores, or whether
      antenatal steroids were used. In phase II, the 66 consecutive, ventilator
      dependent, outborn infants with average, and median, gestational age of 28 weeks
      were compared. The infants receiving surfactant prior to transport, when compared
      to the infants that got it after transport (9 hours later), did not do any
      better. There was 6% more survival without bronchopulmonary dysplasia in the
      group receiving surfactant after transport (65.2% versus 59.3%, p = 0.665). The
      infants receiving surfactant after transport were off the ventilator sooner (95%
      C.I. 6.0-28.7 versus 11.8-25.9 days) and discharged from the perinatal center
      earlier (95% C.I. 37.8-70.8 versus 47.9-69.0 days). Furthermore, arterial blood
      gases before and after transport reveals that there were no short-term advantages
      in administering surfactant prior to transport when compared to waiting for
      reevaluation at the perinatal center. These findings suggest that surfactant can
      be used safely prior to the interhospital transport of preterm infants, but this
      treatment does not seem to confer benefit over waiting for reevaluation, and
      possible surfactant treatment, at the tertiary perinatal center.

PMID- 8863954
TI  - Brief communications: one option for speedy publication.

PMID- 8863955
TI  - Centric relation treatment.

PMID- 8863956
TI  - Centric relation treatment.

PMID- 8863957
TI  - Centric relation treatment.

PMID- 8863958
TI  - Lip adaptation to simulated dental arch expansion. Part 1: Reliability and
      precision of two lip pressure measurement mechanisms.
AB  - Understanding the influence of lip and tongue pressure on tooth position requires
      a reliable method of measuring pressure. A transducer with a beam mechanism has
      been used extensively in the past. A transducer with a diaphragm mechanism has
      been recently introduced. Comparative in-vivo tests of these transducers have not
      been published. The purpose of this study was to investigate transducer
      reliability and precision. Transducers were placed intraorally in 22 subjects,
      and two lip pressure measurements were recorded. Paired t-tests and interclass
      correlations were used to evaluate repeatability and reliability. The error of
      the method was analyzed for each transducer type. Both transducer types produced
      measurements that were repeatable and reliable. The error was smaller for the
      diaphragm transducer. The diaphragm transducer is more precise.

PMID- 8863959
TI  - Lip adaptation to simulated dental arch expansion. Part 2: One week of simulated
      expansion.
AB  - An increase in resting lip pressure and the resulting disruption of the intraoral
      pressure equilibrium may be responsible for the poor stability found with
      orthodontically expanded dentitions. Passive expansion strategies seek improved
      stability by altering lip pressure, thus creating a new equilibrium. One of these
      strategies has been shown to alter pressure favorably. However, pressure changes
      associated with conventional expansion need to be studied before conclusions
      regarding the superiority of passive expansion can be drawn. The purpose of this
      study was to examine lip pressure changes after 1 week of simulated conventional
      expansion. Twenty-two subjects agreed to wear a mandibular expansion-simulating
      stent full-time for 1 week. Resting pressure was measured in the midline and
      right canine areas. Midline lip pressure decreased significantly after 1 week.
      Resting pressure was measured in the midline and right canine areas. Midline lip
      pressure decreased significantly after 1 week while pressure in the canine area
      did not change significantly. This finding suggests an adaptive response that
      varies according to anatomic location.

PMID- 8863960
TI  - A study of maximum bite force during growth and development.
AB  - Bilateral bite force was measured in a sample of 457 subjects (231 males and 226
      females) from 6 years through 20 years. The mean maximum bite force was found to
      increase from 78 Newtons at 6 to 8 years to 176 Newtons at 18 to 20 years. While
      earlier studies have shown adult males have a greater mean bite force than
      females, this difference is not evident during growth and development. Gender
      related bite force difference likely develops during the postpubertal period in
      association with greater muscle mass development in males.

PMID- 8863961
TI  - Dimensional differences in the craniofacial morphologies of groups with deep and
      shallow mandibular antegonial notching.
AB  - Certain craniofacial characteristics were identified on the lateral cephalograms
      of 40 untreated subjects with shallow mandibular antegonial notches and 40
      subjects with deep notches. Subjects with shallow notches demonstrated more on
      the morphological characteristics usually associated with horizontal mandibular
      growth patterns than did subjects with deep notches, and their mandibles were
      positioned more protrusively. In general, the mandibles of the shallow notch
      subjects proved to be longer than mandibles of the deep notch subjects. On
      average, mandibles with deep notches showed greater gonial angles, deeper
      posterior ramus notch depths, and larger occlusal plane inclinations. The total
      anterior facial height of shallow notch subjects was much smaller than that of
      the deep notch subjects. The maxillae in deep notch subjects were more retrusive
      in relation to the cranial base when compared with the shallow notch subjects. A
      discriminant analysis was used to determine which combinations of variables were
      most consistently related to either deep or shallow mandibular antegonial
      notches. Eighty percent (80%) of the cases were classified correctly as deep or
      shallow notch cases by means of this discriminant function.

PMID- 8863962
TI  - A tongue retaining device and sleep-state genioglossus muscle activity in
      patients with obstructive sleep apnea.
AB  - To define the effect of a tongue retaining device (TRD) on genioglossus (GG)
      muscle activity in seven obstructive sleep apnea subjects, two overnight sleep
      studies were carried out with two TRDs. TRD-A had no anterior bulb and
      incorporated two electrodes to record GG electromyographic (EMG) activity. TRD-B
      had a bulb and it had electrodes similar to those in TRD-A. Episodes of
      apnea/hypopnea (AH) were analyzed during both rapid eye movement (REM) and non
      REM (NREM) sleep. The peak GG muscle activity was measured for the breath
      immediately before the AH (pre-AH), for the first (first-E) and last (last-E)
      inspiratory efforts during the AH, and for the first breath after the AH (post
      AH). The time lag between the peak GG EMG activity and the maximum inspiratory
      effort was calculated. The AH index decreased with both TRDs. The peak GG EMG
      activity preceded the maximum inspiratory effort throughout the periods, however
      the time lag changed considerably with TRD-A. The time lags with TRD-A and TRD-B
      differed significantly for the first-E and the last-E during NREM sleep and for
      the first-E during REM sleep. The TRD reduces AH severity, normalizes the time
      lag, and counteracts fluctuating GG EMG activity observed when no bulb is
      present.

PMID- 8863963
TI  - Laser-aided degradation of composite resin.
AB  - The removal of residual composite resin after debonding orthodontic brackets
      often creates surface scratches, enamel loss, and enamel tearouts. If the Nd:YAG
      laser could selectively degrade the resin without damaging the underlying tooth
      structure, these problems might be eliminated. The purpose of this study was to
      determine the effectiveness of the Nd:YAG laser in degrading composite resin
      within a time frame that will not cause pulpal damage. Minimal lasing times and
      optimum frequencies were determined by testing the compressive strengths of resin
      cylinders exposed to laser radiation for 2, 3, 5, 10, or 15 seconds at
      frequencies of 60, 80, or 100 Hz. The optimum condition was determined to be a 3
      second lasing time at a frequency of 100 Hz. Cylinders of composite resin were
      divided into four groups consisting of: (1) resin, (2) resin with a laser
      enhancing dye, (3) resin lased for 3 seconds at 100 Hz, and (4) resin with the
      dye which was lased for 3 seconds at 100 Hz. The compressive strengths of the
      four groups were statistically compared. The resin groups that were lased for 3
      seconds at 100 Hz showed a 75% reduction in compressive strength. The results of
      this study demonstrate that dual wavelength pulsed Nd:YAG laser energy, when used
      within the parameters described here, will degrade the mechanical properties of
      composite resin, thereby offering the potential for a quick and efficient method
      of removing residual composite resin.

PMID- 8863964
TI  - Extraction of maxillary second molars in the treatment of Class II malocclusion.
AB  - The results of treatment following the extraction of maxillary second molars for
      Class II correction were evaluated. Records (cephalograms, orthopantomograms, and
      models) of 32 patients treated with maxillary second molar extraction were
      analyzed. Cephalograms taken before and after treatment were traced and 18
      variables were compared. Changes in the axial inclination of the erupted third
      molars relative to the occlusal plane were measured on the orthopantomograms. The
      form and the position (eruption in occlusion, rotations) of the maxillary third
      molars were evaluated on the models. The average treatment time was 26 months.
      The results of this study show significant changes of the angles SNA, SNB, ANB,
      1/4:SN, and the distances 1-NPog, and 1-APog, as well as significant effects on
      the soft tissue profile. In 19 cases examined 4 years postretention, all
      maxillary third molars had erupted into occlusion with a mesial contact point and
      acceptable mesiodistal axial inclination.

PMID- 8863965
TI  - Recording condylar movement with two facebow systems.
AB  - Two different articulator systems are commonly used by orthodontists to reveal
      the maxillomandibular relationship for improved diagnosis and treatment planning.
      The purposes of the study were: (1) to compare the SAM and the Panadent
      articulator systems when recording condylar discrepancies for the same patient;
      (2) to evaluate the interchangeability of the SAM estimated facebow when mounting
      to the Panadent articulator; and (3) to evaluate the direction of condylar
      movement between centric relation (CR) and centric occlusion (CO). Maxillary and
      mandibular impressions, CO and CR bite registrations, and SAM and Panadent
      facebow recordings were taken for 37 patients. There were no statistically
      significant differences between the SAM and the Panadent systems (p > 0.05).
      However, the SAM facebow should not be used when mounting to the Panadent
      articulator. In most cases, the condyle moves down and back when the subject
      bites into maximum intercuspation.

PMID- 8863966
TI  - The effect of rapid maxillary expansion on conductive hearing loss.
AB  - The effects of rapid maxillary expansion (RME) on conductive hearing loss were
      investigated in 14 subjects (11 females and 3 males). The subjects ranged in age
      from 10 years 4 months to 16 years 9 months (mean age 12 years 11 months +/- 1
      year 9 months) and had narrow maxillary arches and conductive hearing loss.
      Hearing levels were determined by means of pure-tone audiometric records. Three
      records were taken for each subject. The first was taken before RME, the second
      after sufficient midpalatal suture opening was achieved (mean = 15 days), and the
      third after the retention period (mean = 4.5 months). All the audiometric records
      were assessed by an otolaryngologist. Changes in both hearing level and air-bone
      gap were investigated by means of analysis of variance. It has been determined
      that hearing improved at a statistically significant level (P < 0.05) after the
      active treatment period, but that the improvement reversed at the end of the
      retention period. Five patients experienced significant and stable hearing
      improvement over the duration of this study.

PMID- 8863967
TI  - A three-year clinical trial using a glass ionomer cement for the bonding of
      orthodontic brackets.
AB  - Recent clinical studies measuring orthodontic bracket failure, when using glass
      ionomer cement as an adhesive, have reported a wide range of percentages of
      bracket failure. The present study recorded bracket failure over a 3-year period,
      longer than had been previously measured. Seventeen participants were randomly
      assigned to one of two treatment groups, either using glass ionomer cement or
      composite resin for bonding. In each group, brackets were bonded to incisors,
      canines, and premolars. Bracket failure was measured over the duration of
      comprehensive orthodontic treatment for all participants. Brackets bonded with
      the glass ionomer cement were more likely to fail (log-rank test; P < or =
      0.022). This difference was clinically significant. At the present time, the
      disadvantage of extra bracket failures appears to outweigh potential advantages
      when considering glass ionomer cement for the routine bonding of orthodontic
      brackets.

PMID- 8863969
TI  - Permanent lip augmentation using autologous breast implant capsule.
AB  - Permanent augmentation of lip volume can be achieved either with autologous or
      nonautologous implants. The constant risk of infectious complications remains the
      disadvantage of nonautologous implants. Likewise, autologous implants of dermis,
      fat, or fascia are prone to reabsorption and require an additional donor
      incision. In several patients undergoing revisional aesthetic breast
      augmentation, grafts of scar capsule were utilized for lip augmentation. Results
      at 10 months demonstrate persistent volume enhancement.

PMID- 8863968
TI  - Effect of applying chlorhexidine antibacterial agent on the shear bond strength
      of orthodontic brackets.
AB  - The purpose of this study was to determine whether the application of
      chlorhexidine as an antibacterial agent affects the shear bond strength and
      debonding failure modes of orthodontic brackets. Thirty-six recently extracted
      human premolars were cleaned and randomly assigned to one of three groups:
      prophylaxis with pumice only prophylaxis using a 13,500 ppm fluoridated pumice,
      and prophylaxis with pumice followed by application of 0.12% chlorhexidine paste.
      All teeth were etched with a 37% phosphoric acid gel and metal orthodontic
      brackets were bonded to each tooth using the same bonding system. The teeth were
      mounted in phenolic rings and stored in deionized water at 37 degrees C for 72
      hours. A Zwick Universal Testing Machine was used to determine shear bond
      strengths. The residual adhesive on the enamel surfaces was estimated using the
      Adhesive Remnant Index. The analysis of variance was used to compare the various
      groups. Significance was predetermined at P < 0.05. The results indicated that
      there were no significant differences in bond strengths between the chlorhexidine
      , fluoride-, and nonfluoride-treated teeth (P = 0.233). The Chi-Square test
      evaluating the residual adhesive on the enamel surfaces also showed no
      significant differences (P = 0.456) between the various groups. In conclusion,
      the use of chlorhexidine and/or fluoride prophylactic pastes does not
      significantly affect shear bond strength nor bond failure location of orthodontic
      brackets.

PMID- 8863970
TI  - The management of pigmented lesions of the nail bed.
AB  - Pigmented lesions of the nail bed, especially without a history of trauma,
      represent a diagnostic challenge to the clinician. These lesions are often
      categorized as melanonychia striata (MS), which refers to any linear tan-brown
      black pigmentation of the nail bed. The differential diagnosis of MS includes
      subungual hematomas, onchomycosis nigricans, junctional nevi, melanoma in situ
      (MIS), and malignant melanoma (MM). Our algorithm at the New York University
      (NYU) Medical Center for the treatment of pigmented lesions of the nail bed is
      presented. A histopathologic diagnosis with any evidence of melanocytic atypia,
      however subtle, requires absolute confirmation by complete excision. The absence
      of a clear margin or recurrence requires total nail bed excision and
      reconstruction using a full-thickness graft. The diagnosis of MIS is similarly
      treated. The surgical management of subungual MM is discussed. All cases of MM of
      the hand treated at NYU were reviewed. In all, 30 patients were treated from 1982
      to 1995. Follow-up ranged from 6 months to 13 years. In our series, there were 8
      cutaneous and 22 subungual melanomas. There was a marked delay in treatment of
      both groups, with subungual melanomas more often erroneously treated as other
      pathology prior to correct diagnosis. The 5-year survival rate was 100% for
      patients with cutaneous lesions, but only 80% for those with the subungual
      variety. There was a statistical difference in the depths of the lesions
      (subungual, 3.68 mm; cutaneous, 1.36 mm) with a p-value of 0.008. The role of
      elective lymph node dissection in the absence of clinical metastases as well as
      intraoperative sentinel lymphatic mapping remains controversial and is discussed.

PMID- 8863971
TI  - Thenar flap rehabilitated: a review of 20 cases.
AB  - The thenar flap is a satisfactory reconstruction technique for the treatment of
      extensive loss of the distal phalanx of the index and middle fingers. As we
      observed in this series of 20 patients, this flap is reliable and provides tissue
      that closely matches the missing finger pulp. Flap sensibility is good (average
      Weber of 6.5 mm). Transferring a distally based flap prevents proximal
      interphalangeal joint contracture and allows the surgeon to better reconstruct
      the outlines of the distal phalanx, thereby reducing the risk of a clawed nail.
      Finally, we did not observe major postoperative complications at the donor site.

PMID- 8863972
TI  - Femur lengthening with a vascularized tibia bone flap.
AB  - A vascularized tibial bone flap based on a single nutrient vessel has been
      previously proposed for use in long-bone reconstruction. While the routine use of
      the tibia for donor bone tissue is precluded by its essential weight-bearing
      function, in select cases it provides a useful alternative to standard donor bone
      sources. Cadaver dissection was performed to confirm the endosteal and periosteal
      vascular anatomy of the tibia. The presence of a consistent nutrient vessel was
      confirmed. Selective dye injection demonstrated a dual cortical blood supply
      based on both the endosteal nutrient vessel and multiple periosteal perforator
      vessels. Inclusion of both vascular supplies maximizes perfusion of bone and
      periosteum, thus potentially optimizing bone healing and osseous union. Based on
      these findings, the vascularized tibial bone flap was applied to a clinical case.
      A 45-year-old male veteran sustained a right proximal femur fracture in a motor
      vehicle accident. Multiple attempts at fusion with open reduction, internal
      fixation, grafting, and nonvascularized fibular onlay strut with cerclage wires
      were all unsuccessful. The patient presented with a chronic right femur nonunion
      with painful pseudoarthrosis; frozen knee joint; and an internally rotated, 20.3
      cm shortened, nonfunctional lower limb. Femur length proximal to the nonunion was
      less than 15 cm. A maximum amputation stump length is recommended for optimal
      prosthetic function. A 15-cm pedicled tibial bone flap based on the posterior
      tibial endosteal and periosteal vascular supply was reversed and plated to the
      proximal femur to provide a stump of adequate length to optimize prosthetic
      fitting and function. The tibia is essential for normal weight-bearing, but in
      select cases may be sacrificed for use in long-bone reconstruction. Expanded use
      of tibial vascularized allografts in long-bone reconstruction may be made
      possible following future development of effective and safe immunosuppressive
      therapy. Transfer based on the posterior tibial pedicle, which includes the
      endosteal nutrient vessel as well as the periosteal supply via the tibialis
      posterior muscle, maximizes bone perfusion. The pedicle is of sufficient length
      to be used for positioning the tibia in the thigh or for free transfer to distant
      sites.

PMID- 8863973
TI  - The effects of chronic ketorolac tromethamine (toradol) on wound healing.
AB  - Intramuscular ketorolac is a commonly used nonsteroidal anti-inflammatory (NSAI)
      agent for analgesia in surgical patients. Increasing numbers of surgical patients
      are chronically taking some form of an NSAI drug. We examined the effects of
      "chronic" intramuscular ketorolac on the healing of a closed linear surgical
      wound in the rat. Wistar rats were pretreated with 4 mg per kilogram per day
      ketorolac intramuscularly prior to receiving dorsal incisional wounds. The
      ketorolac treatment was continued and after 2 weeks the wounds were excised and
      separated with a tensiometer to measure mechanical properties. Breaking strength
      was directly measured, tensile strength was calculated, and collagen
      concentrations at the wound site were determined. A significant decrease in the
      mean breaking strength was seen in the ketorolac-treated animals when compared to
      controls. The ketorolac-treated animals had a mean tensile strength less than the
      controls, although this difference did not reach statistical significance. The
      mean collagen concentration of the ketorolac-treated wounds was significantly
      less than the untreated wounds. Use of ketorolac for just 1 week prior to surgery
      in rats produced a significant decrease in the breaking strength of their wounds.
      With the increasing use of ketorolac in surgical patients as well as the
      increasing use of oral NSAI drugs, more study of this effect is warranted.

PMID- 8863974
TI  - Musculofascial flaps based on the dorsalis pedis vascular pedicle for coverage of
      the foot and ankle.
AB  - Soft-tissue reconstruction of the foot and ankle has long presented challenging
      problems for the plastic surgeon. Limitations of available local tissue, the need
      for specialized tissue, and donor site morbidity restrict the options available
      to the reconstructive surgeon. In an effort to solve these difficult problems, we
      have begun to use musculofascial flaps based on the branches of the dorsalis
      pedis artery. We present our early experience of 5 patients treated with an
      extensor digitorum brevis muscle flap with fascial extensions often containing
      the contents of the first web space. Our patients ranged from 6 to 60 years in
      age and included 4 males and 1 female. The etiologies of the wounds were
      secondary to trauma (N = 2), complications of surgery for rheumatoid arthritis (N
      = 2), and were secondary to a defect following resection of an arteriovenous
      malformation (N = 1). The flaps had antegrade blood flow in 3 patients and
      reverse flow in 2 patients. The flaps were covered with a split-thickness skin
      graft and the donor site was closed primarily. The donor sites healed without the
      need for further surgery. One patient required additional procedures. This flap
      proved to be both versatile and effective for closure of difficult wounds of the
      foot and ankle.

PMID- 8863975
TI  - Free flap coverage for knee salvage.
AB  - Soft-tissue reconstruction using free flaps was reviewed in 11 consecutive knee
      wounds complicated by joint exposure or adjacent osteomyelitis and unavailability
      of adequate local flaps. Ten free muscle flaps and one fasciocutaneous flap were
      used successfully. Eight limbs presented with wide exposure of the knee joint,
      including 4 patients with wound infection involving the joint. Three other
      patients suffered osteomyelitis immediately adjacent to the knee. All knees were
      successfully salvaged with a single free flap operation, except for one knee that
      required a second free flap after flap necrosis. Follow-up in nine flaps ranged
      from 7 weeks to 19 months (mean, 12 months). For patients without preexisting
      conditions affecting the knee, free flap coverage provided excellent return of
      knee function. The choice of recipient vessels was determined mainly by the
      region of the knee requiring coverage. The recipient arteries utilized included
      the distal superficial femoral artery, anterior tibial artery, popliteal artery,
      and small arteries, which included the saphenous artery and descending branch of
      the lateral circumflex femoral artery. The use of small arteries and venae
      comitantes as recipient vessels increased the effective reach of the free flaps
      and eliminated the need for vein grafts.

PMID- 8863976
TI  - Treatment of earlobe keloids with surgery plus adjuvant intralesional verapamil
      and pressure earrings.
AB  - Treatment for keloids remains less than ideal. Previous discouraging results
      prompted a change in the author's standard treatment for keloids to surgery plus
      adjuvant intralesional verapamil and pressure earrings. Intralesional verapamil
      (2.5 mg per milliliter) was administered 7 to 14 days after keloid removal and
      again approximately 1 month after removal when possible. Between 0.5 ml and 2.0
      ml was administered each time, depending on the size of the keloid. Patients were
      instructed to wear pressure earrings essentially continuously for a minimum of 6
      months after excision. Thirty-five African American patients with 45 earlobe
      keloids were treated with this regimen. Information regarding recurrence was
      obtained by follow-up, mail, or phone call from 31 patients (89%) with 40 keloids
      (89%). Minimum follow-up for inclusion was 6 months and average follow-up was 28
      months. Twenty-two keloids (55%) in 16 patients (52%) were cured by this
      treatment modality. There were no significant differences in recurrence rates
      related to sex, age, keloid size, length of time the keloid was present, how long
      the ears had been pierced, and how many verapamil injections were received. There
      was a trend toward an increased recurrence rate for previously treated keloids.
      Though not optimal, this regimen is superior to some previously evaluated
      regimens.

PMID- 8863977
TI  - Repair of incomplete cleft earlobe.
AB  - The repair of incomplete clefts of the earlobe by just freshening the edges and
      suturing them in apposition may result in an abnormal, pointed earlobe. We
      present a modification of the technique described by Pardue, preserving the hole
      for an earring and preventing the pointed earlobe. Two skin suture lines, in
      opposing directions, maintain the natural curved contour of the earlobe.

PMID- 8863978
TI  - The use of cryopreserved microvenous allografts in the venous system without
      immunosuppression: an experimental study.
AB  - Autogenous vein grafts are currently the number one choice in microsurgical
      practice for managing vessel length discrepancies. A significant percentage of
      these grafts is used in the venous system. Allografts may serve as a viable
      alternative source of vein grafts. Few studies in the past have described the use
      of cryopreserved vein grafts (1 mm in diameter) in the venous system. In the
      present study, we cryopreserved the femoral veins of rats and transplanted these
      across rat species (ACI to Lewis) as interpositional vein grafts into a defect in
      the femoral vein. Short-term patencies (21 days), expressions of systemic
      antigenicity, histology, and scanning electron microscopic studies were
      performed. We obtained 100% patencies with fresh control veins and cryopreserved
      veins at 21 days.

PMID- 8863979
TI  - Endoscopic-assisted repair of a malar fracture.
AB  - Although the zygomatic arch can be employed as a key landmark to the accurate
      alignment of a displaced malar fracture, it has been traditionally avoided
      because of the need for a bicoronal incision. Exposure of the zygomatic arch by
      means of the conventional bicoronal incision has several possible disadvantages,
      including an increased risk of blood loss, alopecia, loss of sensation posterior
      to the incision, and traction palsy of the facial nerve. Endoscopic-assisted
      exposure of a zygomatic arch can largely obviate the disadvantages of a bicoronal
      incision and yield this site accessible to reduction and fixation in the routine
      treatment of displaced malar fractures. A case of endoscopic-assisted open
      reduction and internal fixation of a moderately displaced malar fracture is
      presented. In particular, exposure and fracture fixation of the zygomatic arch
      were performed without the need for a bicoronal incision.

PMID- 8863980
TI  - Endoscopic-assisted wire removal and neurolysis.
AB  - Endoscopic-assisted surgery allows remote incision placement and provides an
      illuminated, magnified operative field. We have applied these principles to
      perform neurolysis of the zygomaticotemporal nerve and removal of a fixation wire
      under endoscopic control in a patient with pain and tenderness at the site of a
      previous zygomatic arch fracture. Endoscopic assistance aided dissection by
      placing the incision in a hidden, unscarred area.

PMID- 8863981
TI  - Rodeo thumb: an unusual etiology of avulsion amputation of the thumb.
AB  - Though avulsion amputation of the thumb is a devastating hand injury,
      microsurgical techniques allow for immediate reconstruction and early restoration
      of function. The majority of these injuries occur in the workplace. An uncommon
      cause of thumb avulsion amputation is team roping. Recently, several individuals
      with such injuries presented and underwent successful replantation. Early
      perioperative venous thrombosis in one case led to secondary reconstruction with
      a delayed skin flap. Nonetheless, all patients have returned to full activity
      including team roping.

PMID- 8863982
TI  - Compound rib-latissimus dorsi osteomusculocutaneous flap in reconstruction of the
      upper arm.
AB  - Reconstruction of humeral defects with a pedicled compound rib-latissimus dorsi
      osteomusculocutaneous flap is described. This flap consists of a latissimus dorsi
      musculocutaneous flap and segments taken from two ribs. In addition to the
      advantages of the conventional latissimus dorsi musculocutaneous flap, it enables
      multiple ribs to be transferred to the recipient site. This compound flap
      transfer can be used as a choice for a reconstructive procedure of the upper arm
      combined with humeral defects.

PMID- 8863983
TI  - Giant cell tumor (osteoclastoma) of the mandible: a diagnostic dilemma and a
      therapeutic challenge.
AB  - A recurrent giant cell lesion of bone 4.5 years after initial curettage from the
      mandibular body is described in a 40-year-old premenopausal female patient. Giant
      cell tumor is exceedingly rare in this location and histologically may be
      indistinguishable from giant cell reparative granuloma. The treatment rationale
      for this particular patient was extrapolated from the treatment of giant cell
      tumor in other more commonly involved bones. En bloc resection is indicated
      irrespective of the grade or stage of the tumor, provided satisfactory
      reconstruction can be achieved. The morbidity from tumor treatment should never,
      in any case, exceed the morbidity from the tumor itself.

PMID- 8863984
TI  - Mentosternal pterygium with teratoma.
AB  - A 7-year-old girl with a cervical midline pterygium and teratoma is presented.
      Pterygium (congenital webbing) of the skin is a rare congenital anomaly.
      Teratomas are tumors formed by pluripotential primordial germ cells that
      constitute heterogeneous types of tissues foreign to the organ from which they
      originate. The undefined connection of two conditions of pterygium and teratoma
      in the cervical region is reviewed in this case report.

PMID- 8863985
TI  - Reconstruction of a complex midfacial defect with the folded fibular free flap
      and osseointegrated implants.
AB  - Refinements in microsurgical techniques, plate fixation, and osseointegration
      have changed the conceptual approach to midface reconstruction. Free tissue
      transfer has emerged as the ideal method of reconstructing complex midfacial
      defects. Single-stage bony restoration of the palate and orbital rim using the
      folded fibular osteocutaneous free flap is described. The fibular free flap is
      our first choice for reconstructing complex midfacial defects. The thin, soft,
      pliable tissue is ideal for intraoral and palatal reconstructions. The bone can
      be tailored precisely to fit any desired shape, and forms a sturdy support for
      both orbital and dental prostheses. With a single flap, rapid and reliable
      restoration of midfacial appearance, orbital support, and palatal function can be
      achieved.

PMID- 8863986
TI  - Cystic hygroma of the chest wall: a rare condition.
AB  - Cystic hygroma of the chest wall is a very rare condition. A review of the
      literature showed only 15 cases reported worldwide. The authors report a case of
      cystic hygroma of the chest wall in a male infant 2 months of age that was
      successfully treated with surgical excision in one stage. The diagnosis was made
      by physical examination with transillumination and by its typical sonographic
      pattern. The diagnosis was confirmed by histopathological examination and there
      is no evidence of recurrence after 24 months of follow-up. A review of the
      literature, updating the embryology, classification, and treatment of the
      disease, is also presented.

PMID- 8863987
TI  - Parotid cribriform salivary carcinoma of the excretory ducts.
AB  - Parotid cribriform salivary carcinoma of the excretory ducts (CSCED) is an
      unusual parotid neoplasm with very distinctive histological features. It is a
      highly malignant tumor with a grave prognosis, CSCED is often misdiagnosed, since
      it is uncommon and difficult to distinguish from metastatic adenocarcinomas. The
      neoplasm most often occurs in the parotid gland of middle-aged or older males and
      has the most dismal prognosis of all salivary carcinomas. Little information is
      available in the literature as to the management of this rare tumor. The
      diagnostic features of CSCED are discussed, along with the case management of a
      46-year-old female patient who was treated and remains tumor free after 5 years.

PMID- 8863988
TI  - Cutaneous fibrous histiocytoma with osteoclast-like giant cells.
AB  - We report a case of a rare variant of benign fibrous histiocytoma composed of
      abundant, multinucleated, osteoclast-like giant cells. Local excision with
      negative margins is the treatment of choice.

PMID- 8863989
TI  - Cutaneous lasers: a review.
AB  - Lasers are versatile instruments capable of treating an ever-increasing array of
      cutaneous conditions. Various vascular, pigmented, epidermal, and dermal lesions
      can be selectively destroyed without damaging normal uninvolved skin structures
      by utilizing lasers that correspond to the absorption characteristics of the
      intended target. Recently, lasers have been used with much success in the
      treatment of rhytides, photodamaged skin, and scarring. The rapid development of
      laser technology has made many lasers obsolete that only a few years ago were
      considered state of the art. Lasers are more reliable, emit light at higher
      energies with shorter pulse widths, and at faster delivery rates. As is typically
      the case with high-technology devices, lasers are becoming less expensive and
      more consolidated. For this reason, laser techniques will continue to evolve and
      new indications for their use will, no doubt, be discovered in the near feature.
      Physicians treating the skin are in a unique position to study the clinical and
      histological effects of lasers, as the skin remains an easy-access organ. Laser
      medicine and surgery will continue to be enhanced by the contributions made
      through the investigative efforts of laser surgeons treating the skin.

PMID- 8863990
TI  - The effect of recombinant human interferon alpha B/D compared to interferon alpha
      2b on SIV infection in rhesus macaques.
AB  - The model of simian immunodeficiency virus (SIV) infection in rhesus macaques was
      used to evaluate the effects of recombinant human interferon alpha, Hu IFN-alpha
      2b and Hu IFN-gamma B,D, at two doses. Administration began 1 day prior to
      infection and was continued for 90 days postinfection. Both interferons
      suppressed SIV antigenemia during the treatment period. Following treatment
      animals were monitored for 4 years for rate of disease progression. Neither IFN
      prolonged the asymptomatic period or survival.

PMID- 8863991
TI  - Establishment of an in vitro assay system for screening hepatitis C virus
      protease inhibitors using high performance liquid chromatography.
AB  - The hepatitis C virus (HCV) genome contains the code for a conserved, serine-type
      protease, called NS3, for the processing of the non-structural protein region of
      the viral polyproteins. Furthermore, a related protein, NS4A, is an effector or
      cofactor of NS3 protease activity in the cleavage of NS3-4A, NS4A-4B, NS4B-5A and
      NS5A-5B junctions. To establish an in vitro assay system for the screening of
      those enzyme inhibitors that inhibit the protease NS3-4A, we prepared a maltose
      binding protein-NS3-NS4A fusion protein and a synthetic peptide substrate that
      mimics the NS5A-5B junction. Cleavage of the synthetic peptide was analyzed by
      reversed-phase high performance liquid chromatography (HPLC). We showed that the
      enzymatic activity of the NS3-NS4A fusion protein was enhanced in comparison to
      the NS3 protein alone. The assay conditions for optimum NS3-4A protease activity
      were determined to be pH 7.6 and 37 degrees C. In addition, we evaluated several
      protease inhibitors using the same HPLC assay system. The activity of HCV
      protease NS3-4A was inhibited by 2714.4 microM diisopropyl fluorophosphate, 270.8
      microM N-tosyl-L-lysyl chloromethyl ketone, and 825.5 microM chymostatin. The
      results of the present study indicated that the synthetic peptide substrate and
      HPLC assay system are suitable for studying HCV protease activity and may
      facilitate the development of anti-HCV therapeutic reagents.

PMID- 8863992
TI  - Response to interferon treatment decreases with epidermal dedifferentiation in
      condylomas.
AB  - After interferon (IFN) treatment of patients with condyloma acuminatum, groups
      clinically proven to be responders or nonresponders were selected, and cellular
      parameters that might influence the clinical response were studied in
      pretreatment biopsies by reverse transcription polymerase chain reaction (RT
      PCR). The nonresponders were found to express higher amounts of cellular
      proliferative markers, such as proliferating cell nuclear antigen (PCNA), cyclin
      A, and cdc 2 kinase, but lower levels of growth suppressor genes (TGF-beta 1, TGF
      beta 2 and p53) before IFN treatment. The responders retained the epidermal
      keratinization, except for some signs of hyperproliferation (K6, K16
      cytokeratins). In addition, the nonresponders showed a shift in the
      keratinization pattern to a mucosal or fetal type, as evidenced by high
      expression of the K18, K6, K16 and K13 cytokeratins but decreased K5, K14 and K10
      levels before treatment. The expression of the human papillomavirus (HPV) genes
      is consistent with these differentiation patterns. The crucial conclusion to be
      drawn from this study is that those condylomas whose pretreatment phenotype most
      closely resembles that of normal epidermis respond to IFN treatment, whereas
      those more akin to nonkeratinizing epithelia fail to respond, i.e. the resistance
      of condylomas to IFN treatment is correlated with dedifferentiation.

PMID- 8863993
TI  - Differential effect of recombinant human and mouse interferons on replication of
      herpes simplex virus type 1 in mouse cells.
AB  - Pretreatment of murine (BALB/3T3) cells with either murine or recombinant hybrid
      human B/D interferon (IFN) blocked the release of infectious herpes simplex virus
      type 1 (HSV-1) from treated cells. The block in replication was not due to an
      effect on attachment of HSV-1 to the target cells or to toxic effects of IFN.
      Immunoblot analyses showed that murine IFN significantly reduced the expression
      of virus-specific proteins in IFN-treated cells. In contrast, B/D IFN had no
      major effect on the expression of viral proteins in treated cells. In support of
      the above observation, electron microscopy of virus-infected cells displayed
      formation of nucleocapsids within the nucleus of IFN-treated cells. However, the
      expression of glycoproteins B and D was reduced in B/D IFN-treated cells. These
      results suggested that murine IFN blocked HSV-1 replication at an early stage
      whereas B/D IFN inhibited HSV-1 replication at a late stage in virus
      morphogenesis.

PMID- 8863994
TI  - A rapid assay for determination of antiviral activity against human
      cytomegalovirus.
AB  - RC256, the recombinant human cytomegalovirus (HCMV) which expresses beta
      galactosidase, was used as a tool for rapid screening of compounds for antiviral
      activity. The effective concentration of antiviral compound needed to inhibit
      RC256 was identical to the concentrations needed to inhibit other strains of HCMV
      as measured by plaque reduction assay or virus yield reduction assay. Measurement
      of beta-galactosidase activity in infected cell lysates allowed determination of
      effective concentrations 48 h postinfection with results comparable to the
      longer, more laborious assays.

PMID- 8863995
TI  - Anti-hepatitis B virus activity of N-acetyl-L-cysteine (NAC): new aspects of a
      well-established drug.
AB  - N-acetyl-L-cysteine (NAC) is commonly administered as an antidote against
      acetaminophen intoxication and is the preferred agent in the treatment of
      pulmonary diseases. It is furthermore commonly considered that it restrains human
      immunodeficiency virus (HIV) replication by scavenging reactive oxygen
      intermediates (ROI) and thus suppressing activation of nuclear factor kappa B (NF
      kappa B). We show here that NAC is in addition able to inhibit hepatitis B virus
      (HBV) replication, but by a mechanism independent of the intracellular level of
      reactive oxygen intermediates. Treatment of HBV-producing cell lines with NAC
      resulted in an at least 50-fold reduction of viral DNA in the tissue culture
      supernatant within 48 h. This decrease of viral DNA and thus of virions in the
      tissue culture supernatant is caused by a disturbance of the virus assembly,
      rather than by a reduction of viral transcripts. Our data strongly suggest a
      potential use of this well-established, non-toxic drug for the treatment of HBV
      infection. Since NAC, in contrast to interferon, exerts its anti-HBV activity at
      a posttranscriptional level, a combination of NAC with the established interferon
      therapy could also be considered.

PMID- 8863996
TI  - A comparison of accuracy between clinical examination and magnetic resonance
      imaging in the diagnosis of meniscal and anterior cruciate ligament tears.
AB  - A prospective and retrospective study was undertaken to compare the accuracy of
      magnetic resonance imaging (MRI) with clinical examination in diagnosing meniscal
      and anterior cruciate ligament (ACL) tears. Pathological findings were then
      confirmed during arthroscopy. One hundred fifty-four patients clinically
      diagnosed with a meniscal or ACL tear who ultimately had arthroscopic knee
      surgery were evaluated; 100 patients underwent clinical examination followed by
      MRI, and 54 underwent clinical examination alone. The presence or absence of
      meniscal and ACL tears was confirmed during arthroscopy. The accuracies of
      clinical examination and MRI were compared for the 100 patients who underwent
      both clinical examination and MRI. The accuracy of MRI was 75% for medial
      meniscal tears, 69% for lateral meniscal tears and 98% for ACL tears. The
      accuracy of clinical examination was 82% for medial meniscal tears, 76% for
      lateral meniscal tears and 99% for complete tears of the ACL. Furthermore, the
      accuracy of clinical examination for the 54 patients who underwent clinical
      examination alone was not significantly different from the accuracy of clinical
      examination in the 100 patients who also underwent MRI. There was no significant
      difference between the accuracy of clinical examination and MRI in the diagnosis
      of meniscal and ACL tears and, overall, MRI contributed to treatment in only 16
      of 100 cases. Based on these findings, we feel that MRI, except in certain
      circumstances, is an expensive and unnecessary diagnostic test in patients with
      suspected meniscal and ACL pathology.

PMID- 8863997
TI  - A prospective study comparing the accuracy of the clinical diagnosis of meniscus
      tear with magnetic resonance imaging and its effect on clinical outcome.
AB  - A prospective, single-blind study of 57 consecutive knees with an initial
      clinical diagnosis of a torn meniscus was completed to test the hypothesis that a
      routine preoperative magnetic resonance imaging (MRI) scan could improve accuracy
      over clinical diagnosis alone. The overall accuracy for the clinical diagnosis of
      meniscal tear was 80.7% and the corresponding accuracy for MRI was 73.7%.
      Surgical pathology was found in all knees at arthroscopy. Relying blindly on MRI
      to determine surgical intervention would have resulted in inappropriate treatment
      in 35.1% of the knees. A surgeon can safely rely on the clinical diagnosis of
      meniscal tear alone and will find surgical pathology in almost all cases. Relying
      on MRI alone without using clinical judgment may lead to inappropriate treatment
      in a high percentage of cases. Clinical examination alone is at least as accurate
      as MRI. MRI did not prevent "unnecessary surgery" in any case. MRI should be
      reserved for confusing or special cases.

PMID- 8863998
TI  - Comparison of anterior cruciate ligament reconstructions using patellar tendon
      autograft or allograft.
AB  - Seventy-eight of 113 consecutive patellar tendon anterior cruciate ligament
      reconstructions (autograft, 47 of 66; allograft, 31 of 47) were evaluated at an
      average of 34 months. Reconstructions were compared with Lysholm and Tegner knee
      rating scales, physical examination findings, instrumented laxity values, single
      leg hop distances, and isokinetic strength results. Lysholm scores > or = 90 were
      achieved by 69% of autograft patients versus 67% of allograft patients. Desired
      Tegner activity scores were achieved by 80% of autograft patients versus 74% of
      allograft patients. Patellofemoral signs and symptoms were absent in 40% of
      autograft patients versus 44% of allograft patients. Side-to-side laxity
      differences < or = 3 mm were achieved in 80% of autograft patients versus 70% of
      allograft patients. Single-leg hop scores > or = 90% of the nonoperated leg were
      obtained in 76% of autograft patients versus 81% of allograft patients.
      Isokinetic results between groups were also similar. Traumatic ruptures were
      sustained by four allograft patients at an average of 11 months postoperatively
      compared with no traumatic ruptures in the autograft group (P = .011). This was
      the only difference of statistical significance.

PMID- 8863999
TI  - Strength of the fixation of patellar tendon bone grafts using a totally
      absorbable self-reinforced poly-L-lactide expansion plug and screw. An
      experimental study in a bovine cadaver.
AB  - In a bovine cadaver study, bone-tendon-bone graft fixation strength with
      different graft geometry and fixation devices was measured to evaluate the
      fixation strength of totally absorbable implants: a 6.0-mm expansion plug and 6.3
      mm screw both made of self-reinforced polylactide (SR-PLLA). Comparison was made
      with 6.5-mm AO cancellous screw. Maximum tensile force to dislodge the bone plug
      from the bone tunnel was recorded. First, two preliminary tests were performed.
      In the first test, triangular bone plugs were used (9-mm diameter). The direction
      of the pull force was parallel to the bone tunnel. The maximum tensile forces
      were 786 N in femoral insertions and 625 N in tibial insertions, mean. After
      this, we evaluated the influence of change in the pullout direction. In the
      second test, a circular bone plug was used with no fixation but the direction of
      the pull force was parallel to the tibial or femoral axis and the bone plug (10
      mm diameter) was in a 30 degrees to 40 degrees angle to the direction of the pull
      force and it was compressed to the tunnel (9-mm diameter). The maximum tensile
      forces were 783 N in femoral insertions and 695 N in tibial insertions, mean. In
      the final third test, we used a curved saw in harvesting the graft. This made a
      half-circular bone block with a diameter of 12 mm. The maximum tensile force to
      dislodge the bone plug from the bone tunnel was recorded and the pull force was
      in a 30 degrees to 40 degrees angle to the tunnel. The results were evaluated
      with Student's t-test and Mann-Whitney U-test. With the AO screw, the maximum
      tensile force to dislodge the bone plug from the bone tunnel was 2,113 +/- 407 N
      (mean +/- standard deviation) and it was better than the fixation strength of the
      SR-PLLA expansion plug, 1,379 +/- 328 N (P = .009, t-test) and better than the
      fixation strength of SR-PLLA screw, 1,454 +/- 230 N (P = .007, t-test). However,
      the maximum tensile force of both SR-PLLA implants in all measurements in the
      third test were above 1,100 N and it seems that the initial strength of totally
      absorbable implants is enough for the clinical use.

PMID- 8864000
TI  - Ankle arthrodesis using an arthroscopic method: long-term follow-up of 34 cases.
AB  - Thirty-four ankle arthrodeses performed using an arthroscopic technique were
      followed for an average of 8 years. The fusion rate was 97% and the average time
      to fusion was 9 weeks; 86% of patients had good or excellent functional results.
      There were no wound infections or neurological injuries. There was one malunion
      and one additional minor complication. The arthroscopic method uses an abrader to
      denude the joint surfaces of cartilage, followed by screw fixation. The average
      time to fusion is significantly less than other ankle arthrodesis techniques,
      which hastens the recovery period. The shorter time to fusion is likely a result
      of the minimal soft tissue stripping that is performed during the procedure. The
      low morbidity of this technique eliminates the need for hospitalization in most
      cases. There were no long-term adverse sequelae. This is the largest reported
      series of arthroscopic ankle arthrodeses.

PMID- 8864001
TI  - Femoral interference screw placement through the tibial tunnel: a radiographic
      evaluation of interference screw divergence angles after endoscopic anterior
      cruciate ligament reconstruction.
AB  - Fifty patients who underwent single-incision arthroscopically assisted anterior
      cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone autograft
      were reviewed. All procedures were performed using a technique for placement of
      the femoral interference screw that reduced the divergence between the femoral
      interference screw and the femoral bone plug. This technique includes securing
      the femoral interference screw by placing the screw driver through the tibial
      tunnel, anterior to the tibial bone plug. Using this technique, 8% of our
      patients had significant femoral bone plug and interference screw divergence;
      however, no patients had a divergence angle of greater than 15 degrees in either
      the anteroposterior or lateral planes. None of our patients were noted to have
      divergence angles consistent with decreased pullout strength. We had no
      complications caused by screw driver placement, and we did not experience any
      graft injury. We believe that adequate femoral bone plug and interference screw
      alignment can be achieved by using this technique during single-incision
      endoscopic ACL reconstruction.

PMID- 8864002
TI  - Reactions of meniscal tissue after arthroscopic laser application: an in vivo
      study using five different laser systems.
AB  - In many clinical and in vitro studies, the effect of laser radiation on meniscal
      tissue was examined. Clinical studies referred to clinical criteria like
      swelling, effusion, and pain to evaluate laser effects. In vitro studies showed
      the laser effect in the moment of cutting the tissue. But the effect of laser
      radiation on biological tissue also depends on the vital reaction of the tissue.
      So, the real extent of tissue damage caused by laser irradiation can only be
      examined in long-term in vivo studies. This was the purpose of this study.
      Seventy-two knees of pigs underwent arthroscopic meniscal cuts in the anterior
      horn of the medial meniscus. The pigs were divided into 6 groups: The first 5
      groups were operated with 5 different laser systems: Neodym: YAG 1,440-nm
      wavelength; Nd:YAG 1,064-nm wavelength, Excimer, Holmium:YAG, and CO2. The sixth
      group was operated with mechanical punches. From each group, the menisci of the
      pigs were examined macroscopically and by light-microscope after survival periods
      of 0, 2, 6, 12 weeks. Results were as follows. (1) All laser systems caused
      greater damage to the meniscal tissue than mechanical instruments. (2) This
      damage was a biological reaction of the tissue, characterized by a necrotic zone
      surrounding the meniscus cut. (3) This necrotic zone was not visible
      intraoperatively but only 2, 6 and 12 weeks after operation. The diameter of the
      necrotic zone ranged between 1.5 nm and 9 mm. (4) Meniscus cuts with mechanical
      instruments showed no necrotic zone in the surrounding tissue. (5) Laser cuts in
      the meniscus caused more extensive healing reaction than cuts with mechanical
      instruments. (6) The quality of this healing reaction varied with the different
      laser systems: the Nd:YAG 1,064-nm, Ho:YAG, and CO2 laser caused only an
      incomplete healing because the tissue repair showed by tissue growing from the
      synovial edge into the defect only. The Nd:YAG 1,440-nm wavelength and Excimer
      led to tissue growing from the synovial edge and to remodeling of original
      meniscal tissue, recognizable by reduction of the necrotic zone. Arthroscopic
      surgeons should be aware that the damage to meniscus tissue caused by a laser is
      much greater than can be seen intraoperatively and is much greater than the
      damage caused by mechanical punches. The healing reaction of the tissue is more
      extensive after laser application than after use of mechanical instruments.
      Results of in vitro studies on the tissue damage caused by lasers are
      insufficient to describe the whole extent of laser effects on living tissue.

PMID- 8864003
TI  - Metal and biodegradable interference screws: comparison of failure strength.
AB  - The purpose of this laboratory investigation was to determine if there was any
      difference in the force required to pull out a patellar bone-tendon-bone graft
      from a femoral bone tunnel when secured by an interference screw of different
      materials, metal or biodegradable. The tibial end of the bone-tendon-bone graft
      was placed in the femoral tunnel. A 9-mm metal interference screw was used on the
      left side, and a 9-mm biodegradable screw was used on the right to secure the
      graft. Ultimate load to failure was determined by Instron testing. The average
      load before failure for the graft secured by the metal screw was 436 Newtons and
      for the biodegradable screw was 565 Newtons. A statistical significance was not
      demonstrated because there was wide range of loads between donor specimens,
      probably because of variations in bone density.

PMID- 8864004
TI  - Captured shoulder: a complication of rotator cuff surgery.
AB  - Thirteen patients who developed restrictive subdeltoid adhesions after rotator
      cuff repair were identified. These patients underwent second-look arthroscopy and
      takedown of adhesions at an average of 37 weeks after their index surgery.
      Clinical findings include pain and restricted motion that does not yield to
      manipulation under anesthesia. Arthroscopic findings are subdeltoid adhesions and
      a chondral lesion (companion lesion) of the humeral head articular surface.
      Patients were reevaluated at 26 weeks after their release of adhesions.
      Prerelease and postrelease University of California, Los Angeles (UCLA) scores
      average 14.8 and 30.1, respectively. Prerelease and postrelease UCLA pain scores
      averaged 2.6 and 7.7, respectively. Prerelease and postrelease range of motion
      was as follows: Flexion, 141/158; abduction, 123/141; internal rotation, 47/69;
      and external rotation, 53/74. The authors have proposed a theory to explain the
      clinical and arthroscopic findings in this subgroup of patients who are
      dissatisfied after rotator cuff repair. A technique for and the results of
      release of the subdeltoid adhesions also are reported.

PMID- 8864005
TI  - Single versus two-incision arthroscopic anterior cruciate ligament
      reconstruction.
AB  - The purpose of this study was to compare single (endoscopic) versus two-incision
      arthroscopic anterior cruciate ligament reconstruction using bone-patellar tendon
      bone in a population of young athletes. All patients followed a similar
      postoperative rehabilitation program. The Lysholm knee score, the International
      Knee Documentation Committee Score, KT-1000 arthrometric measurements, Lachman
      tests, pivot shift tests, isokinetic and functional testing, and perioperative
      complications were used to compare the two techniques. Anteroposterior and
      lateral radiographs were also evaluated and compared. Group I comprised 51
      patients who underwent two-incision arthroscopic ACL reconstruction. The average
      age was 19.8 years, with a range of 18 to 22. The average follow-up in this group
      was 31 months (range, 24 to 43 months). Group II, the endoscopic group, consisted
      of 31 patients with an average age of 19.4 years (range, 18 to 22). The average
      follow-up was 25 months (range, 24 to 31 months). There were no significant
      differences between the two groups using subjective, objective, and functional
      criteria. There did appear to be a trend toward a residual pivot glide in the
      endoscopic group, but this did not achieve statistical significance. Radiographic
      analysis demonstrated an increased incidence of screw divergence in the
      endoscopic group. Intraoperative complications were more common with the
      endoscopic method.

PMID- 8864006
TI  - Comparison of screw post fixation and free bone block interference fixation for
      anterior cruciate ligament soft tissue grafts: biomechanical considerations.
AB  - Endoscopic (single-incision) anterior cruciate ligament (ACL) reconstruction with
      bone patellar tendon bone can usually be secured with interference screws on the
      femur and tibia. Infrequently, patella alta, which results in a longer tendinous
      component of the graft construct, can result in construct mismatch, resulting in
      a large portion of the tibial bone plug extruding from the tibial tunnel,
      requiring graft fixation with staples or a suture/screw and post technique. This
      study investigated the hypothesis that initial graft fixation could be enhanced
      if the bone plug was removed and press fit into the tibial tunnel and then
      secured with an interference screw in the scenario of graft construct mismatch.
      Initial biomechanical fixation strengths of bovine patellar tendon were compared
      using a screw and post suture fixation compared with a free bone plug, which was
      removed from the graft and sandwiched along with the soft tissue with an
      interference screw. Twenty-eight bovine knees were randomly divided into two
      groups. Graft fixation was performed with a free bone plug excised from the
      tibial tubercle portion of the bone tendon bone construct. Fixation was achieved
      with a cannulated 9-mm x 20-mm interference screw. Fixation was performed in
      group 2 patients with a Krackow suture of no. 5 Ticron secured over a screw and
      post. An Instron materials testing system was used and loading rates at 1 mm/sec
      until failure was performed. Statistically significant differences were noted for
      load to failure and stiffness (P < .001). Group 1 specimens' mean maximum load to
      failure was 669 N (range, 511 to 819 N), whereas the load to failure for group 2
      patients was 374 N (range, 266 to 491 N). Group 1 stiffness was 90 N/mm (range,
      50 to 122 N/m) compared with a mean stiffness of 24 N/m (range, 16 to 33 N/m) for
      group 2 knees. In our bovine model, free bone block interference fixation was
      stronger and stiffer than fixation using sutures tied over a post. This fixation
      method of securing a soft tissue graft with an interference screw warrants
      further clinical investigation and may offer an improvement to the alternative of
      suture/post fixation.

PMID- 8864007
TI  - The effect of nonablative laser energy on the ultrastructure of joint capsular
      collagen.
AB  - This study was designed to evaluate the effect of laser energy at nonablative
      levels on the ultrastructure of joint capsular collagen. The femoropatellar joint
      capsules of six mature New Zealand white rabbits were harvested immediately after
      death. Specimens were divided into three treatment groups (5, 10, and 15 watts)
      and one control group. Laser energy was applied using a holmium: YAG laser.
      Transmission electron microscopy showed significant ultrastructural alterations
      in collagenous architecture for all laser treatment groups, with increased fibril
      cross-sectional diameter for each of the treated groups. The fibrils began to
      lose their distinct edges and their periodical cross-striations at subsequently
      higher energy densities. A morphometric analysis showed that each subsequently
      higher laser energy caused a significant increase in collagen fibril diameter.
      Ultrastructural alteration of collagen fibril architecture caused by the thermal
      effect of laser energy is probably the dominant mechanism of laser-induced tissue
      shrinkage.

PMID- 8864008
TI  - Local anesthesia in outpatient knee arthroscopy: a comparison of efficacy and
      cost.
AB  - This study was performed to compare the efficacy, cost-effectiveness, and safety
      of general, regional, and local anesthesia when performing outpatient knee
      arthroscopy. The study consisted of two portions. A retrospective review of 256
      outpatient knee arthroscopies was performed. The types of anesthesia used were
      general endotracheal, regional (epidural or spinal), and local. Comparisons were
      made between operative procedure, anesthesia procedure time, need for
      supplemental anesthesia, recovery room time and cost, pharmaceutical cost, and
      complications. A prospective study consisted of 100 consecutive outpatient knee
      arthroscopies performed using local anesthesia. Data identical to the
      retrospective portion were obtained. Visual analog scales were used in a patient
      questionnaire completed at the first postoperative visit to assess patient
      satisfaction with local anesthesia. The retrospective data showed similar
      demographics and operative procedures performed in the three study groups. The
      difference between operative time and total anesthetic time for the local group
      was 35 minutes less than for regional, and 23 minutes less than for the general
      group. These differences were statistically significant (P < or = .05). Total
      pharmaceutical cost was significantly less for the local group (P < or = .05).
      Recovery room cost for the local anesthesia group averaged $134 compared with
      $450 for regional and $527 for general. This difference was significant (P < or =
      .05). There were 19 complications with general anesthesia, 16 with regional
      anesthesia, and 2 with local. There were two regional and two local cases that
      needed subsequent general anesthesia. The prospective data showed nearly
      identical time and cost data. The patient questionnaire showed nearly universal
      acceptance and satisfaction with the use of local anesthesia. The use of local
      anesthesia for outpatient knee arthroscopy is safe, effective, and well accepted.
      The use of local anesthesia was shown to save a minimum of $400 per case compared
      with the other anesthetic methods studied.

PMID- 8864009
TI  - What would you do? Acute extension block caused by anterior cruciate ligament
      tear: a case report.
AB  - Acute knee locking is usually attributed to a displaced meniscus tear. This case
      involved late diagnosis of mechanical extension block caused by anterior
      displacement of a torn anterior cruciate ligament (ACL) with impingement in
      extension. Definitive reconstruction was delayed after debridement of the ACL
      stump to improve preoperative range of motion. Despite this, the patient still
      had difficulty regaining extension after surgery. Early treatment of mechanical
      extension block may facilitate motion recovery after ACL reconstruction.

PMID- 8864010
TI  - Tenosynovial giant-cell tumor arising from the anterior cruciate ligament of the
      knee.
AB  - The localized form of tenosynovial giant-cell tumor is rarely located
      intraarticularly, especially in the large weight-bearing joints. We report the
      first case of localized, intraarticular tenosynovial giant-cell tumor arising
      from the anterior cruciate ligament of a knee in which locking and effusion had
      occurred. After arthroscopic removal of this tumor, the patient became
      asymptomatic.

PMID- 8864011
TI  - Arthroscopic shaving of a hematoma after total knee arthroplasty.
AB  - A large hematoma in the immediate postoperative period after total knee
      arthroplasty may result in wound breakdown and skin necrosis, leading to a delay
      in recovery or prosthetic infection and failure. Needle aspiration is ineffective
      because of the viscous nature of the hematoma. This is the first report of the
      use of an arthroscopic shaver to evacuate such a hematoma in an 81-year-old woman
      6 days after a primary total knee arthroplasty. This allowed for immediate pain
      relief, early mobilization, and primary wound healing.

PMID- 8864012
TI  - The dimpling phenomenon: articular cartilage injury overlying an occult
      osteochondral lesion at the time of anterior cruciate ligament reconstruction.
AB  - The authors report the arthroscopic finding of articular cartilage "dimpling"
      when a probe is placed onto the discrete chondral area involved over the
      geographic bone bruise incurred during traumatic anterior cruciate ligament
      disruption. As we develop an understanding of the pathology and sequelae of this
      osteochondral injury, this finding may be useful to document injury extent and
      possibly guide treatment including weight-bearing status and rehabilitation.

PMID- 8864013
TI  - Arthroscopic bone peg fixation in the treatment of osteochondritis dissecans in
      the knee.
AB  - An arthroscopic method for the treatment of osteochondritis dissecans lesions in
      the knee is described. The technique involves using autogenous bone pegs for
      arthroscopic transfixion of femoral osteochondritis dissecans (OCD) lesions. The
      method represents a simple biological alternative for arthroscopic fixation of
      OCD lesions.

PMID- 8864014
TI  - Arthroscopic-assisted posterior cruciate ligament reconstruction using patellar
      tendon autograft: a technique for graft passage.
AB  - During arthroscopic posterior cruciate ligament (PCL) reconstruction, passage of
      the graft into the knee joint may be difficult, especially when using the
      patellar tendon. Because of the angle of passage, the bone block ends may become
      entangled or caught on the superior edge of the posterior tibial tunnel when
      passing the graft from the tibia to the femur. The use of a blunt trocar through
      the posteromedial portal avoids impingement of the bone block against the edge of
      the tibial tunnel. This method uses the pulley principle and permits the graft to
      pass freely into the knee. This method has been used successfully by the authors
      in more than 40 PCL arthroscopic reconstructions.

PMID- 8864015
TI  - Femoral bone plug recession in endoscopic anterior cruciate ligament
      reconstruction.
AB  - Graft tunnel mismatch is a constant challenge in endoscopic ACL reconstruction
      with bone-patella tendon-bone allograft. Strategies for addressing this situation
      on the tibial side which include staple or suture fixation may compromise the
      postoperative pullout strength of the graft. We describe our technique for
      recession of the femoral bone plug as a solution to this problem and present our
      preliminary experience in a series of 100 consecutive patients followed-up to 1
      year. Interference screw fixation was consistently achieved in both tunnels and
      recession did not influence anterior-posterior displacement by KT arthrometry.

PMID- 8864016
TI  - Hemolysis in membrane plasma separators: is it caused by filter or user?

PMID- 8864017
TI  - Metabolic acidosis in hemodialysis patients: a study of prevalence and factors
      affecting intradialytic bicarbonate gain.
AB  - The correction of uremic acidosis is one of the goals of hemodialysis; however,
      despite acceptable hemodialysis protocols, metabolic acidosis remains a common
      problem. The prevalence of acidosis and significance of factors affecting
      bicarbonate flux during hemodialysis were studied. A cohort of 70 stable patients
      receiving high-efficiency hemodialysis for at least 4 months was studied
      prospectively over a 1-year period. Twenty patients (28%) had a mean predialysis
      serum bicarbonate of less than 21 mEq/L. The patients with or without metabolic
      acidosis had similar mean net ultrafiltration and percent ultrafiltration, but
      acidotic patients had a higher percent increase in bicarbonate during
      hemodialysis (35 +/- 12 versus 27 +/- 10 [p = 0.008]). The latter suggests an
      increased net daily acid gain in patients with metabolic acidosis (1.19 +/- 0.32
      mEq/kg versus 1.05 +/- 0.35 mEq/kg [p = 0.04]). A review of factors affecting
      intradialytic bicarbonate gain showed that predialysis serum bicarbonate
      (diffusive gradient) was the most significant with a demonstrated linear
      relationship between these two variables (R2 0.51). The role of dialysance and
      blood flow, assessed together using percent urea reduction, was minor as was the
      effect of ultrafiltration. At our level of dialysis delivery, prevalence of
      metabolic acidosis is low, and dialysis-related factors do not contribute to the
      persistence of metabolic acidosis. Net daily acid gain was higher in acidotic
      patients and accounts for the long-term maintenance of metabolic acidosis. For
      individual dialysis treatments, the diffusive gradient is the most important
      determinant of bicarbonate gain, with only a minor role being demonstrated for
      percent urea reduction and ultrafiltration rate.

PMID- 8864018
TI  - Blood density monitoring during dialysis.
AB  - Continuous monitoring of blood density (BD) was preformed in 4 stable dialysis
      patients in 20 sessions using a density meter based on a mechanical oscillator
      technique. Mean predialysis and postdialysis BDs were 1.0427 +/- 0.0031 g/cm3 and
      1.0502 +/- 0.0055 g/cm3, respectively. For similar predialysis to postdialysis
      total body water reduction, significant difference in the mean BD increase was
      found between hypotensive and nonhypotensive groups (1.29 +/- 0.07%, 0.47 +/-
      0.12%, respectively; p < 0.001). Eight hypotensive episodes occurred during 6
      sessions. The mean value of the blood density changes slope (dBD/dr) during the 5
      min preceding a hypotensive episode increased about 2.5 times more than did the
      mean of the predialysis to postdialysis blood density slope (27.6 +/- 2.2
      g/cm3.min.10(-5), 10.5 +/- 0.4 g/cm3.min.10(-5), respectively; p < 0.001) under
      the condition of a constant ultrafiltration rate of 18.9 +/- 0.6 ml/min.
      Continuous monitoring of blood density allows abrupt change in plasma volume to
      be identified and seems to have a potential utility to the prevention of
      symptomatic hypotension episodes in patients receiving hemodialysis.

PMID- 8864019
TI  - Reduction of plasma fibrinogen, immunoglobulin G, and immunoglobulin M
      concentrations by immunoadsorption therapy with tryptophan and phenylalanine
      adsorbents.
AB  - Immunoadsorption (IA) therapy with tryptophan (TR-350) or phenylalanine (PH-350)
      adsorbents has been used to reduce the concentration of serum antibodies in human
      lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification
      have been reported to reduce the level of fibrinogen, which affects the blood
      properties. In this study we investigated the effects of IA therapy using both
      adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8
      patients were treated with TR-350, and 5 patients were treated with PH-350).
      During each session I plasma volume (2.8 +/- 0.4 L of plasma) was processed
      through the immunocolumn and then returned to the patient together with the blood
      cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM
      concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350;
      p < 0.04 for PH-350). There was a positive correlation between the degree of
      reduction of plasma proteins and the number of IA treatments given. A
      nonparametric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was
      used for statistical analysis. We conclude from our study that IA therapy
      effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be
      considered a valuable alternative to other blood purification methods.

PMID- 8864020
TI  - Use of an integrated sideport for diagnosis and management of decreased flow
      rates in a programmable implanted insulin delivery system. Implantable Insulin
      Pump Trial Study Group.
AB  - The aim of this study was to develop procedures for the diagnosis and nonsurgical
      management of decreased insulin flow in an implantable programmable pump for long
      term intraperitoneal or intravenous insulin delivery featuring a sideport.
      Patency of the catheter lumen was tested by measuring the time needed for
      sideport pressure to decrease by 50% after the injection of 0.1 ml of buffer
      solution. Pumping unit performances were assessed by measuring the volume of pump
      pulses after diverting the pump flow at the sideport. A catheter flush with
      buffer solution through the sideport was effective in clearing 79% of
      intraperitoneal and 84% of intravenous catheter occlusions. Washing the pumping
      unit with an alkaline solution after diverting pump flow at the sideport was
      effective in dissolving insulin aggregates inside the pumping unit and in
      restoring normal pump flow. These procedures were associated with a 1.3% rate of
      hypoglycemic episodes.

PMID- 8864021
TI  - Pancreatic islet macroencapsulation: a new device for the evaluation of
      artificial membrane.
AB  - We propose a new device especially designed to test membranes for islet
      macroencapsulation. It is composed of three independent parts: a support made of
      three polytetrafluoroethylene rings, the membrane that forms the walls of the
      encapsulation chamber, and a collagen gel that immobilizes the islets. Studies of
      this device were performed with the AN69 membrane. After 2 months of implantation
      in the peritoneal cavity of rats, the empty device was found to be biocompatible,
      referred to as weak cellular adhesion. In vitro the encapsulation preserved the
      peak of insulin release in response to high glucose during a perifusion test
      (0.36 +/- 0.02 microU/ml/islet for free or encapsulated islets). As a result of
      the collagen gel, the morphological aspect and functional activity were still
      preserved after 7 days of culture. In vivo xenotransplantation into diabetic mice
      normalized the fasting glycemia up to 30 days. Numerous macrophages adhered to
      the outer surface of the membrane, and a layer of cells emerging from the
      destruction of islets covered the inner surface. In addition, the morphological
      aspect of many islets was altered. By showing that the AN69 membrane was only
      partially efficient for islet xenotransplantation, this new device proved to be
      of interest for testing a variety of membranes.

PMID- 8864022
TI  - Effects of heparin coating of cardiopulmonary bypass circuits on in vitro oxygen
      free radical production during coronary bypass surgery.
AB  - During cardiopulmonary bypass (CPB) oxygen free radicals (OFR) are formed, which
      can mediate reactions damaging tissue components. Blood contact with artificial
      surfaces during CPB leads to an activation of leukocytes, which are one of the
      sources of the OFR. Heparin coating of the CPB circuit reduces granulocyte
      activation. In the present study, the heparin-coated circuits with noncoated
      cardiotomy reservoirs (Group HC) were compared with noncoated, otherwise similar
      CPB sets (Group C). In each group, 8 patients were operated on for coronary
      revascularization. The release of granulocyte granule proteins myeloperoxidase
      (MPO) and lactoferrin (LF) was evaluated. Production of OFR in the whole blood
      and in the granulocyte suspension were measured by chemiluminescence (CL). In
      both groups the whole blood CL declined during CPB. The whole blood CL induced by
      serum-opsonized zymosan, when enhanced by luminol, was significantly lower in
      Group HC at 45 min after CPB start (68 +/- 6% of initial values in Group HC vs.
      87 +/- 6% in Group C, mean +/- SEM) and 30 min after protaminization (54 +/- 6%
      of initial values in Group HC vs. 72 +/- 6% in Group C, mean +/- SEM), and CL was
      significantly higher in Group HC at CPB end (83 +/- 5% of initial values in Group
      HC vs. 67 +/- 5% in Group C, mean +/- SEM) when enhanced by lucigenin. CL of
      isolated granulocytes showed no significant differences between the groups.
      Release of MPO at CPB end and of LF 45 min after start of CPB and at CPB end were
      significantly lower in the heparin-coated CPB circuits.

PMID- 8864023
TI  - In vitro function and durability assessment of a novel polyurethane heart valve
      prosthesis.
AB  - While flexible-leaflet, central-flow prosthetic heart valves promise relief from
      anticoagulation therapy, they continue to be restricted by inadequate durability.
      In consequence, a novel trileaflet valve, made entirely from polyurethane, has
      been developed. A batch of 6 consecutively manufactured polyurethane valves was
      subjected to hydrodynamic function and accelerated fatigue testing. Computerized
      data acquisition and control systems have been introduced to improve valve
      testing methodologies. In terms of hydrodynamic function, the polyurethane valve
      demonstrates transvalvular pressure gradients similar to those for a
      bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow
      significantly less than those for either the bioprosthetic valve or a bileaflet
      mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without
      failure has been exceeded by all 6 polyurethane valves in accelerated fatigue
      tests with 2 valves remaining intact after 674 million cycles (equivalent to
      approximately 17 years) in continuing tests. Highspeed photography revealed
      considerable differences in leaflet motion between valves cycled at accelerated
      and physiological rates.

PMID- 8864024
TI  - Factors influencing vortex development in a model of a skeletal muscle ventricle.
AB  - A video technique was used to visualize flow patterns in a pulsatile model of a
      skeletal muscle ventricle (SMV). The shape and duration of SMV filling/emptying
      curves were determined by the stroke action of a computer-controlled piston pump.
      In this way we examined the effect of filling duration and injection volume on
      the flow structures. To simulate the interaction between the left ventricle and
      the SMV in the proposed clinical application, two filling/emptying regimes were
      employed with the period of each SMV cycle being either equal to or twice that of
      a typical cardiac cycle. Vortex formation at the inlet to the ventricle was a
      feature of both flow cycles during filling for all the combinations of injection
      volume and filling duration considered. When a pacing ratio of 1:1 was simulated,
      SMV filling was immediately followed by ejection, and the formed vortex was
      expelled. Under this flow regime, fluid in the apical end of the ventricle
      remained undisturbed. When the pacing ratio was 2:1, however, the quiescent
      period that followed filling allowed time for the formed vortex to travel a
      significant distance toward the apical end of the ventricle. Under certain
      conditions of injection volume and flow rate, the vortex reached the apex by the
      end of the quiescent period. We suggest that a ventricle connected to the aorta
      by a single, valveless conduit would require a flow regime that included a
      significant period of quiescence after filling. This would allow the vortex to
      reach and displace blood that would otherwise stagnate in the apex, thereby
      reducing the risk of thrombus formation.

PMID- 8864025
TI  - Optimal control algorithm for pneumatic ventricular assist devices: its
      application to automatic control and monitoring of ventricular assist devices.
AB  - We developed a control and monitoring unit for pneumatic ventricular assist
      devices (VADs), which provides optimal fill and empty control and real-time
      evaluation of pump performance. The flow signal of the inflow cannula is
      integrated every beat to yield pump filling volume per pump diastole. The
      ejection signal is triggered when pump filling reaches a preset level. The
      instantaneous mean flow of each beat (stroke volume/cycle length) is compared
      with the previous beat, and the threshold level is readjusted to optimize flow.
      This feedback loop is repeated every beat, and pump filling is immediately
      adjusted to yield maximum pump flow. Simultaneously the mean flow of every 10
      beats is compared with that of the previous 10 beats; then, the ejection time is
      readjusted to optimize flow. Initial clinical application of this unit supports
      its effectiveness and reliability.

PMID- 8864026
TI  - Hemolytic characteristics of a pivot bearing supported Gyro centrifugal pump
      (C1E3) simulating various clinical applications.
AB  - Centrifugal blood pumps are playing a key role in circulatory mechanical assist
      systems including cardiopulmonary bypass (CPB), right and left ventricular assist
      devices (RVAD and LVAD), percutaneous cardiopulmonary support (PCPS), and
      extracorporeal membrane oxygenation (ECMO). Each of these circulatory assist
      systems requires specific flow and pressure conditions. In vitro hemolysis tests
      were performed using five compact mock loops with flow and pressure set
      equivalent to clinical conditions. These studies determined the hemolytic
      characteristics and clinical applicability of the pivot bearing-supported Gyro
      centrifugal pump with an eccentric port (C1E3) compared with the Bio-Medicus pump
      (BP-80). Normalized index of hemolysis (NIH) values of the C1E3 were less than
      those of the BP-80 under all conditions; in particular, they were significantly
      less in the CPB, LVAD, and RVAD conditions. In addition, linear correlation was
      observed between NIH values, rotational pump speed (RPM), total pressure head
      (delta P), and flow rate (Q) with both the C1E3 and BP-80: NIH = a(RPM/Q) + b,
      NIH = c(delta P/Q) + d. However, the slopes (a and c) of these equations were
      smaller with the C1E3 than those with the BP-80, which suggests that the C1E3 has
      decreased hemolytic characteristics when increasing the RPM and delta P. In other
      words, the increase of RPM and delta P results in less shear stress with the C1E3
      than with the BP-80. One cause of these decreased hemolytic characteristics of
      the C1E3 is thought to be less pump power loss against an increase of RPM and
      delta P than with the BP-80. Furthermore, the average exposure time is shorter
      with the C1E3 than with the BP-80 because the priming volume of the C1E3 (30 ml)
      is smaller than that of the BP-80 (80 ml). From the point of both shear stress
      and exposure time, the C1E3 has less hemolytic features than the BP-80.

PMID- 8864027
TI  - Sweep gas flowrate and CO2 exchange in artificial lungs.
AB  - A simple analysis and graphic result are presented for characterizing the
      dependence of CO2 exchange on the sweep gas (ventilating gas) flowrate in
      artificial lungs. The analysis requires no knowledge of the device-specific mass
      transfer characteristics of an artificial lung, nor does it require detailed
      mathematical modeling or computer simulation. Rather, it uses appropriate
      normalization to establish generic features of the gas flow dependency of CO2
      exchange that are applicable to all artificial lung devices. Principal results
      are that the transition from relatively gas flow-sensitive to gas flow
      insensitive CO2 exchange occurs at sweep gas flowrates of approximately 40-60
      times the CO2 exchange rate. Achieving a CO2 exchange rate within 85% of maximal
      (for a given oxygenator and blood-side conditions) requires a sweep gas flowrate
      of no less than approximately 50 times the nominal CO2 exchange rate. When the
      sweep gas flowrate is less than 20 times the CO2 exchange rate, CO2 exchange is
      highly gas flow dependent and less than one-half the maximal possible rate.

PMID- 8864028
TI  - A volume-controlled liquid ventilator with pressure-limit mode: imperative
      expiratory control.
AB  - Liquid ventilation with perfluorocarbon (PFC) has been considered to offer
      advantages over gas ventilation to respiratory distress syndrome patients. We
      developed a volume-controlled liquid ventilator with pressure-limit mode;
      inspiration is performed mechanically with an actuator under the preset limit of
      the intratracheal pressure (Paw); expiration is performed by gravity assistance.
      Oxygenation and CO2 removal of PFC are done with a membrane oxygenator. An
      endotracheal tube with a Paw monitor line was placed in 5 rabbits weighing 2.7 +/
      0.6 kg, and liquid ventilation was conducted with the condition that the upper
      and lower limits of Paw were 20 and -20 mm Hg, respectively. The best arterial pH
      and gas tension were examined. The averaged arterial pH and gas tension were
      examined. The averaged arterial pH. Pao2, Paco2, and Sao2 were 7.45 mm Hg, 369 mm
      Hg, 46.2 mm Hg, and 100% at the best values, respectively. Ventilatory conditions
      at the best values were as follows: ventilation rates, tidal volume peak Paw,
      average Paw, and trough Paw were 5-15 (11 +/- 4) times/min, 13.3-17.3 (15.6 +/-
      1.4) ml/kg, 5-18 (12 +/- 5) mm Hg, -7-4 (-1 +/- 4) mm Hg, and -20(-)-6 (-13 +/-
      5) mm Hg, respectively. Pressure-limit control of the system worked well, but in
      the initial 3 animals, fluorothrax, that is the leakage of PFC into thoracic
      cavity, was recognized at the Paw from 20 to 25 mm Hg after the upper pressure
      limit was raised to 25 mm Hg to improve Paco2. The fluorothrax seemed to be
      caused by excess end-expiratory residual volume. An expiratory control mechanism
      appears to be imperative for further improvement of our liquid ventilator.

PMID- 8864029
TI  - Chronic viral hepatitis in childhood.
AB  - In endemic areas infection with hepatitis B virus is a common cause of chronic
      liver disease in childhood. High levels of viral replication and mild ALT
      abnormalities are the rule in children infected perinatally and many of them are
      likely to maintain viral replication through their youth. Conversely about 90% of
      children infected later in life clear HBeAg and achieve sustained remission of
      liver disease before reaching adulthood. The eventual outcome of infection and
      disease in these patients remains unpredictable as reactivation of liver damage
      and viral replication may occur after several years of sustained remission.
      Cirrhosis is a rare and early complication of chronic HBV infection in children,
      and a risk factor for hepatocellular carcinoma. IFN therapy can accelerate HBV
      DNA clearance, improving the spontaneous anti-HBe seroconversion rate in
      Caucasian children by two to three times. Hepatitis delta is the most severe form
      of chronic viral hepatitis in childhood. Cirrhosis can be diagnosed in up to 26%
      of patients at presentation, and few cases respond to IFN therapy. Hepatitis C is
      relatively rare in children. Before the discovery of HCV, blood transfusions were
      the most common source of infection. Hepatitis C is usually a mild, asymptomatic
      disease in otherwise healthy children, but has a poor propensity to spontaneous
      remission over the years. For this reason, and based on the experience in adults,
      IFN treatment is now being evaluated.

PMID- 8864031
TI  - Hepatitis E.
AB  - Hepatitis E has a world-wide distribution and causes substantial morbidity and
      mortality in some developing countries, particularly among pregnant women.
      Hepatitis E virus (HEV) has recently been cloned and sequenced, and new
      diagnostic tests have been developed. These tests have been used to begin to
      characterize the natural history and epidemiological features of HEV infection.
      Experimental vaccines have also been developed that offer the potential to
      prevent hepatitis E. However, much remains to be learned about HEV, including the
      mechanisms of transmission, the reservoir(s) of the virus, and the natural
      history of protective immunity in order to develop effective strategies to
      prevent this disease.

PMID- 8864030
TI  - Recent advances in the molecular biology of hepatitis B virus.
AB  - Hepatitis B virus (HBV) is an enveloped hepatotropic DNA virus. Acute and chronic
      HBV infection causes significant liver diseases such as acute hepatis, fulminant
      hepatitis and chronic active hepatitis that may lead to liver cirrhosis and the
      development of hepatocellular carcinoma. The use of molecular biological
      techniques has substantially improved our understanding of the HBV life cycle. In
      this review, we discuss recent advances that have contributed to a better
      understanding of HBV biology. Recent studies in the understanding of the life
      cycle of HBV such as viral entry, replication, transcriptional regulation, viral
      regulatory proteins, viral assembly and secretion, and nucleic acid based
      approaches to antiviral therapy will be emphasized. These advances in molecular
      biology and relationship to clinical disease will be instrumental in developing
      effective therapeutic approaches for the estimated 300 million individuals
      worldwide chronically infected with HBV.

PMID- 8864032
TI  - Heterogeneity of hepatitis C virus.
AB  - A great deal of information on the molecular heterogeneity of hepatitis C virus
      (HCV) has been achieved since its discovery in 1989. However, little is known
      about the clinical significance of these variations. Based on the degree of
      sequence variation, HCV has been classified into six major groups or types,
      differing by 31-34% at the nucleotide level over the entire virus genome. Each
      type is divided into several subtypes that differ by 20-23% in nucleotide
      sequence. Viruses within the same subtype are up to 10% divergent and, within
      infected individuals, vary by up to 1.5%. Genotype distributions are not
      homogeneous around the world and may reflect both historical and recent
      parenteral routes of transmission. The clinical implication of these genomic
      variations are not yet fully elucidated: genotype 1b has been associated with end
      stage liver disease, including liver cirrhosis and hepatocellular carcinoma, but
      this finding might rather reflect its earlier introduction to the populations
      studied. Consistent evidence exists that types 2 and 3 have a higher response
      rate to interferon treatment than type 1, although the interplay between genotype
      and viral load in determining the response is still unclear. Immunohistochemical
      studies indicate a stronger activation of the endogenous interferon system in the
      liver of patients infected with type 1 compared to those infected with types 2
      and 3, explaining, at least in part, its low responsiveness to exogenous
      interferon treatment. Biological, sequence-dependent variations of genotypes have
      been poorly investigated to date, but differential efficiency of translation
      activity of the 5' non-coding region has been reported. The availability of "in
      vitro" systems for evaluating pathogenetic aspects and neutralization mechanisms
      will improve the present knowledge on this world-wide infectious disease and on
      the clinical usefulness of distinguishing between genotypes.

PMID- 8864033
TI  - Pathogenesis of chronic hepatitis C and associated clinical manifestations.
AB  - In 20% of patients exposed to hepatitis C virus, infection is transient but,
      after a few months, the patient remains susceptible to infection with the same
      strain. Protective immunity is short-lived. This suggests that recovery is
      related to the cellular immune response, which presumably lyses infected cells,
      and that the need during recovery for a virus-neutralizing anti-envelope
      response, is transient. In 80% of patients the infection is persistent, and it
      seems that antigenic variation of the envelope proteins allows the virus to
      escape neutralization by anti-envelope responses. The fact that this antigenic
      variation occurs at a much lower rate in agammaglobulinaemic subjects suggests
      that the major immune pressure producing this variation is humoral. How the virus
      infected cells avoid lysis by cytotoxic T cells, which can be demonstrated in
      small numbers in the infected liver, remains unclear. The recent observation,
      that HCV infects CD8 lymphocytes, raises the possibility that virus infection of
      CD8 cells may impair their function and contribute to persistent infection. The
      mechanisms of production of cryoglobulin and of autoantibody formation are both
      unclear.

PMID- 8864034
TI  - The natural history of hepatitis C.
AB  - The natural history of hepatitis C is complex and still poorly known. Hepatitis C
      virus (HCV) replication can be detected very soon after exposure and, at least in
      the transfusional setting, it persists indefinitely in up to 90% of the cases.
      While liver damage during the acute phase of hepatitis is almost invariably mild
      (fulminant cases are exceptions), chronic sequelae of HCV infection may be severe
      in the long run. Chronic hepatitis C, in fact, is a long-lasting indolent process
      which leads to cirrhosis in approximately 20% of all infected patients.
      Hepatocellular carcinoma is a well-recognized complication of old infections, as
      are a number of extrahepatic manifestations, including type II cryoglobulinaemia.
      The determinants of the severity of the liver disease are still unclear. However,
      the risk of cirrhosis seems to be greater for patients with old infections, those
      infected with the genotype 1b and those with associated conditions. The latter
      are a heterogeneous and increasing group of 'problem' patients, including
      patients who are co-infected with the human immunodeficiency virus (HIV1), or who
      are being treated with cytotoxic or immunomodulating drugs. Data suggest that the
      natural history of hepatitis C is altered in patients with associated conditions,
      and this might have an impact on strategies of patient management and treatment.

PMID- 8864035
TI  - Interferon therapy for chronic hepatitis C.
AB  - Interferon alone is currently the treatment of choice for chronic hepatitis C.
      The optimal treatment regimen continues to be defined and refined by clinical
      studies. The variability of the response to interferon seems to be influenced by
      several factors, including liver histology, viral genotype, level of viraemia,
      number of predominant quasispecies, and perhaps the type of interferon and
      treatment regimen. It is therefore quite likely that, in the future, treatment
      regimens will be tailored to the individual patient in order to maximize the
      likelihood of a beneficial outcome. It is also likely that the increasing
      availability of sensitive, quantitative, and affordable assays of hepatitis C
      viral levels will allow physicians to assess treatment response quite differently
      from the way we do so today. This will change our philosophy such that we will
      begin to view and treat chronic hepatitis C as an infection, instead of simply as
      a liver disease.

PMID- 8864036
TI  - New treatments for chronic viral hepatitis B and C.

PMID- 8864037
TI  - Hepatitis B and C viruses and primary liver cancer.
AB  - The data presented indicate that viral agents (namely, HBV and HCV) are major
      environmental aetiological factors for human primary liver cancer. It is
      important to elucidate the molecular mechanisms further because HCC is one of the
      few examples of virus-related human cancers. In addition, the available evidence
      points to the possibility of at least partial prevention of the tumour by large
      scale vaccination.

PMID- 8864038
TI  - Liver transplantation in virus-induced chronic liver disease.
AB  - The current status of liver transplantation (OLTx) for chronic viral hepatitis is
      reviewed. The major issues addressed include the rate of recurrence of disease,
      its severity and natural history, and the potential for therapy. These issues
      vary markedly for each type of viral hepatitis. The development of new antiviral
      agents for clinical use may change the current restriction on liver
      transplantation for hepatitis B virus (HBV)-related liver disease such that it
      begins to challenge hepatitis C virus (HCV) as the principal indication for OLTx
      world-wide.

PMID- 8864039
TI  - A sex difference in turning bias in humans.
AB  - A large body of literature has documented the existence of individual preferences
      in turning direction among rodents which appear to be dependent on striatal
      dopaminergic mechanisms. Recent work has indicated that humans also demonstrate
      individual turning preferences, and that these preferences may also be related to
      the nigrostriatal dopamine system. We describe here a new method for measuring
      turning preferences in humans and report a sex difference in the magnitude of the
      directional preference. While both males and females tended to turn towards the
      right, this tendency was significantly stronger among females. Analyses of test
      retest reliability across two sessions (1-2 weeks apart) indicated that, in
      general, the rotation task elicited consistent turning biases. However, the
      turning biases of males and of females using oral contraceptives were
      significantly more consistent than those of regularly cycling females. These
      results are compatible with the animal literature and provide indirect evidence
      that ovarian hormones may modulate the mechanism(s) underlying this motor
      asymmetry.

PMID- 8864040
TI  - Systemic administration of anti-NGF antibodies to neonatal mice impairs 24-h
      retention of an inhibitory avoidance task while increasing ChAT immunoreactivity
      in the medial septum.
AB  - Neonatal mice received subcutaneous injections of either antibody against murine
      NGF raised in goat (3 mg, injection volume 50 microliters) or preimmune serum on
      postnatal days 2, 4, 6, 8, 10, and 12. They were tested on postnatal days 15-16
      or 20-21 for learning and 24-h retention of a passive avoidance step-through
      task. Immunostaining for choline acetyltransferase (ChAT) was measured in two
      cholinergic forebrain areas (septum and caudate-putamen) on postnatal day 16 or
      21. Locomotor activity and exploratory behavior in an open-field test were also
      assessed on day 17 or 22, following a single administration of either scopolamine
      (2 mg/kg) or saline solution. While anti-NGF treatment did not affect acquisition
      on day 15, impairment in retention was evident on day 16. On days 20-21, no
      effects were found either on acquisition or on retention capabilities. Analysis
      of ChAT immunostaining revealed a significant increase of ChAT-immunopositive
      cells in the medial septal area in 16-day-old but not in 21-day-old mice.
      Behavior in the open-field test and age-typical response to scopolamine were not
      altered by anti-NGF at either of the two ages considered. These data support the
      view that immunological neutralization of endogenous NGF specifically affects the
      maturation of retention capabilities in altricial rodents, and confirm the
      involvement of forebrain cholinergic mechanisms in early memory processes.

PMID- 8864041
TI  - Effects of the subacute administration of nefiracetam on abnormal behavior in
      aged rats.
AB  - We investigated the effects of nefiracetam on learning and memory by the Morris
      water maze task and water-finding test, and on emotional behavior by forced
      swimming, hole-board and open-field tests in old male Kbl Wistar rats aged 90 and
      108 weeks. In the water maze task, the acquisition of the task in aged rats was
      slower than that in young rats. Subacute administration of nefiracetam (1 and 3
      mg/kg daily) for 24 days tended to shorten the goal latency to escape onto the
      platform in a dose-dependent manner in the retention test, conducted 24 days
      after acquisition training. Nefiracetam (1 mg/kg) administration for 49 days
      decreased the duration of immobility in aged rats in the forced swimming test.
      Locomotor activity in young rats during the dark period was significantly higher
      than that during the light period, while there was no difference in locomotor
      activity between the light and dark periods in aged rats, suggesting that
      locomotor activity during the dark period and nocturnal habits may be impaired in
      aged rats. Subacute administration of nefiracetam for 14 days significantly
      increased the locomotor activity during the dark, but not light, period in a dose
      dependent manner. In addition, nefiracetam given for 38 days, significantly
      shortened the increased time elapsed before animals started exploring the
      environment in aged rats compared with young rats in the water-finding tests.
      These findings suggest that nefiracetam may improve the impaired nocturnal habits
      and some of emotional behavior in aged rats.

PMID- 8864042
TI  - An endpoint, descriptive, and kinematic comparison of skilled reaching in mice
      (Mus musculus) with rats (Rattus norvegicus).
AB  - The forelimb and paw movements of mice were compared with those of rats in two
      skilled reaching for food tasks. Both species could use a single forelimb to
      reach for food, as measured in two different tasks, although performance was
      better and more consistent in rats than in mice. Both species located the food
      using olfaction, and moved from a diagonal supporting pattern in which support
      and postural adjustments came mainly from the contralateral to reaching forelimb
      and the ipsilateral to reaching hindlimb. Forelimb movements in both species
      could be divided into 3 components: (1) a transport component in which the limb
      is lifted, aimed, advanced, and pronated over the food using mainly movements of
      the upper limb; (2) a manipulatory component in which the digits are pronated
      over the food in an arpeggio movement and in which the digits grasp the food
      using grips that are scaled to the size of the food; and (3) a withdrawal
      component, in which the paw is supinated by adduction by the upper arm and by a
      movement about the wrist, as the food is withdrawn and presented to the mouth.
      Kinematic measures showed that the initial velocity of reaching in mice was
      slower than for rats, but otherwise the shape of the velocity curve and the
      trajectory of the limb movement, above and beyond the food pellet, were similar
      in both species. The results suggest that the motor control of reaching in the
      two rodent species is almost the same despite an evolutionary divergence that
      occurred about 20 million years ago. This profile of movement could be useful for
      investigating motor systems in normal mice and it could be applied to the
      analysis of motor systems in mutant and transgenic mice suspected of having motor
      abnormalities.

PMID- 8864043
TI  - Motor dysfunction in a photothrombotic focal ischaemia model.
AB  - The study of behavioural deficits resulting from cerebral infarction in animal
      models of stroke has in the past taken second place to histological assessment.
      This is particularly true of the photothrombotic lesion model. Most tests
      currently used to measure motor deficits use a scoring system to quantify
      parameters such as beam walking. The present study set out to characterise a
      simple and objective assessment for motor impairment in the photothrombotic
      cortical lesion model. Rats were assessed on a number of motor function tests,
      i.e. gross locomotor activity, rotarod, and grip strength. After the
      establishment of stable baselines, cortical photothrombotic lesions were induced,
      after which the animals were re-tested for a further 18 days. The presence of
      cortical photothrombotic lesions significantly imparied the rats' performance on
      the rotarod and grip-strength tests. The deficit observed with the grip-strength
      task appeared 24 h postsurgery, but was much reduced by day 18 postsurgery. The
      rotarod test revealed an effect that took longer to establish, but which was more
      persistent. Gross locomotor activity was not affected. These data suggest that
      bilateral photothrombotic lesions of the prefrontal cortex produce deficits that
      can be detected by rotarod and grip-strength tasks.

PMID- 8864044
TI  - Contribution of egocentric spatial memory to place navigation of rats in the
      Morris water maze.
AB  - Place navigation in the Morris water maze can be directed by memory of the target
      coordinates relative to remote landmarks (allocentric) or by the memory of the
      start-goal route (egocentric). When the start and goal positions remain constant
      and visual cues are eliminated by darkness, memory of the route may become
      decisive. This assumption was tested in 10 male hooded rats using an infrared
      television tracking system allowing navigation training in the dark. In Expt. 1,
      these animals were trained to swim in the dark from the start at the S rim of the
      pool to the goal position in the center of the NW quadrant of the pool. Mean
      escape latencies decreased from 47 s initially to 16 s during the 24 daily
      sessions. Another group of 10 male hooded rats learned the same task in the
      light. Mean escape latencies decreased from 20 s initially to 5 s during 4 daily
      sessions. In Expt. 2, possible allocentric location of the target was tested in
      the same rats by rotating both the start and goal positions by 90 degrees
      counterclockwise (i.e., to E-SW and later to N-SE). Mean escape latency during 5
      days after the first rotation increased to 24 s, but returned back to the
      asymptotic level of 18 s after the second rotation. The same change of the start
      and goal position (from S-NW to E-SW) in the light only increased escape latency
      in the first session. In Expt. 3, both the goal position and route direction were
      changed to N-SW. Surprisingly, the animals rapidly acquired a new heading angle
      at the start and mean escape latencies were not significantly changed. It is
      concluded that overtrained place navigation in darkness can be easily changed to
      a new direction.

PMID- 8864045
TI  - Differential expression of fos-like immunoreactivity in the descending
      projections of superior colliculus after electrical stimulation in the rat.
AB  - In rodent, there is evidence that the orienting behaviour elicited by direct
      stimulation of the superior colliculus (SC) is partly mediated by contralateral
      descending projections, while avoidance-type behaviour is associated with
      ipsilateral descending projections. However, the identity of target structures in
      the brainstem which mediate these different behavioural responses is unknown. The
      c-fos immediate early gene is expressed polysynaptically in neurons in response
      to a wide range of extracellular stimuli, and hence has been proposed as a
      technique for mapping functional pathways. The purpose of this study was,
      therefore, to use the c-fos technique to investigate the functional specificity
      of brainstem regions which are innervated by the two main descending projections
      of the SC. Patterns of fos-like immunoreactivity (FLI) were observed throughout
      the brainstem following electrical stimulation of the SC in Urethane
      anaesthetized rats. Previously, the electrical stimulation had been shown to
      elicit either approach-like or avoidance-like movement. The main results of this
      experiment were; (i) animals in which the stimulation elicited defensive
      behaviour had elevated levels of immunostaining in specific terminal areas of the
      ipsilateral descending projections, e.g. the ventrolateral midbrain/pontine
      reticular formation, the cuneiform area and rostral periaqueductal grey; (ii)
      there was no FLI expression in any of the terminal areas of the crossed
      descending projection, even in animals where the electrical stimulation elicited
      approach. Control experiments showed that the lack of expression in the crossed
      descending pathway was not due to the restricted range of stimulation parameters
      used in the main study, or to the effects of the anaesthetic. In conclusion, this
      experiment was able to identify likely substrates for the mediation of defensive
      reactions elicited by tectal stimulation. However, given the total lack of
      expression in a pathway which is known to be activated, it also provides further
      evidence that c-fos cannot simply be used as a high resolution neuronal activity
      marker for mapping functional pathways.

PMID- 8864046
TI  - Effortful information processing in a spontaneous spatial situation by rats with
      medial prefrontal lesions.
AB  - Previous research has suggested that the rat prefrontal cortex might play a role
      in spatial information processing and in divided attention. More recent work
      showed that the effect of prefrontal lesions is more important when the task
      involves response selection in complex situations. The first aim of the present
      study was to test the effect of lesions of the prelimbic area of the rat
      prefrontal cortex in spatial exploration, a situation involving the processing of
      spatial and non-spatial information, but requiring no response selection. The
      second aim was to manipulate the degree of cognitive effort required by the task.
      The latter effect was tested by manipulating the number of items to explore. Rats
      explored either a simple (3 objects) or a complex (6 objects) situation. We
      reasoned that acquiring spatial information so as to react adequately to spatial
      or non spatial changes involved more effortful processing in the complex
      situation than in the simpler one. The results suggest that the medial prefrontal
      cortex is not crucially involved in effortful processing when the task requires
      no response selection.

PMID- 8864047
TI  - Behavioural effects of ablations of the presumed 'prefrontal cortex' or the
      corticoid in pigeons.
AB  - This study further explored functional similarities of mammalian prefrontal
      cortex and its presumed equivalent in pigeons. Our results show that the
      performance of delayed alternation of pigeons in an Y-maze is impaired following
      ablations of the prefrontal equivalent together with the corticoid but not of the
      corticoid alone. In the same maze, discrimination between vertical and horizontal
      stripes was unimpaired regardless of the lesion. Our results added the following
      new information. (1) Corticoid is not essentially involved in mediation of
      delayed responding. (2) Like monkeys, pigeons take much fewer trials to learn
      delayed alternation in a maze than in an operant chamber. (3) Lesions of the
      pigeon equivalent of the prefrontal cortex impair delayed responding also in the
      new apparatus. (4) These lesions do not impair visual pattern discrimination. Our
      results do not contradict the hypothesis that the postero-dorso-lateral
      neostriatum in pigeons is comparable to the prefrontal cortex in mammals.

PMID- 8864048
TI  - NMDA and non-NMDA sensitive [L-3H]glutamate receptor binding in the brain of the
      Naples high- and low-excitability rats: an autoradiographic study.
AB  - The Naples high-excitability (NHE) and low-excitability (NLE) rat lines,
      selectively bred for high and low activity in a Lat maze, respectively, are used
      as an animal model in the study of hippocampal functions. The aim of this study
      was to investigate the anatomical distribution of N-methyl-D-aspartate (NMDA) and
      non-NMDA sensitive [3H]glutamate receptor binding by quantitative autoradiography
      in the brain of the NHE and NLE rats with a randomly bred line (NRB) as controls.
      Twenty-micron-thick cryostat sagittal sections were incubated at 4 degrees C with
      150 nM [L-3H]glutamate alone or in the presence of 100 microM NMDA or 2.5 microM
      quisqualate (QA). Non-specific binding was determined in the presence of 1 mM of
      non-labeled glutamate. The sections were exposed to tritium-sensitive films for 3
      weeks at 4 degrees C. Quantitative analysis revealed: (1) higher levels of total
      binding in NHE than in NRB and NLE rats in all areas but the cerebellum; (2)
      fewer binding sites for both NMDA and QA receptors and larger binding sites for
      QA receptors in the hippocampus of NLE and NHE rats, respectively; (3) a positive
      correlation between total binding sites and activity level in a Lat maze in all
      areas, except the cerebellar molecular layer with NLE < NHE, which was due to
      differential contribution from NMDA and non-NMDA types. Thus, the brain of the
      NHE rats shows an imbalance between NMDA and non-NMDA sensitive [L-3H]glutamate
      receptors.

PMID- 8864049
TI  - Behavioral changes in Anolis carolinensis following injection with fluoxetine.
AB  - Eight adult male lizards of the genus and species Anolis carolinensis were used
      in this experiment. In order to induce aggressive responding, animals were caged
      separately and daily underwent pairing with another male, during which aggressive
      responses and changes in skin color were measured. After obtaining a baseline
      measure of aggressive responding, animals were injected either with fluoxetine or
      vehicle-controls in a cross-over design. Subjects were then exposed to five more
      days of (non drug) pairing with the intruder male, after which they underwent a
      second trial with fluoxetine/vehicle. Finally, two post-drug paired-trials were
      obtained. Fluoxetine injection significantly reduced the aggressive responding in
      the males while causing the postorbital eyespot to significantly darken. Subjects
      also showed increased aggressivity and skin-color reactivity subsequent to the
      two drug trials, although it is unclear if the fluoxetine, or non-specific
      factors of the injection paradigm, accounted for these changes. These results
      suggest that serotonergic CNS systems tonically regulate aggression in Anolis
      carolinesis, similar to that seen in many other species. They further suggest
      that eyespot-darkening and aggressive responding can be pharmacologically
      dissociated, implicating serotonin in the regulation of this phenomenon.

PMID- 8864050
TI  - Brain sites mediating the discriminative stimulus effects of nicotine in rats.
AB  - Pharmacological studies suggest that the discriminative stimulus (DS) produced by
      nicotine is mediated centrally. The aim of the present study was to identify
      neuroanatomical substrates that mediate the DS properties of nicotine.
      Specifically, the nucleus accumbens, a brain region known to mediate the DS
      effects of amphetamine and cocaine, was investigated using a two-lever operant
      drug discrimination paradigm. Male hooded rats were trained to discriminate
      nicotine (0.2 mg/kg s.c.) from saline with a tandem schedule of food
      reinforcement. Once stimulus control was attained, a randomised sequence of
      nicotine microinjections (2-8 micrograms) was tested for generalisation during
      brief extinction tests. It was confirmed that the stimulus produced by the
      systemic administration of nicotine generalized to nicotine administered
      bilaterally into the dorsal hippocampus, with significant decreases in overall
      response rates. Microinjections of nicotine (1-8 micrograms) into the nucleus
      accumbens failed to produce any dose-related increases in responding on the
      nicotine-appropriate lever although these microinjections also produced
      significant decreases in response rates. Smaller doses (1-4 micrograms) of
      nicotine administered into the fourth ventricle produced characteristic
      prostration responses but these microinjections failed to produce generalization
      in tests carried out 20 min later, when the disabling effects of prostration had
      dissipated. These results suggest that the DS effects of nicotine may be
      mediated, at least in part, through the dorsal hippocampus. Results from intra
      accumbens and intraventricular injections suggest that these regions may not be
      important in mediating the DS effects of nicotine.

PMID- 8864051
TI  - Long-term effects of neonatal ischemic-hypoxic brain injury on sensorimotor and
      locomotor tasks in rats.
AB  - Perinatal ischemia and/or hypoxia in humans are major risk factors for neurologic
      injury that often manifest as sensorimotor and locomotor deficits throughout
      development and into maturity. In these studies, we utilized an established model
      of neonatal ischemic-hypoxia that creates unilateral striatal, cortical, and
      hippocampal damage (Rice III, J.E., Vanucci, R.C. and Brierley, J.B., Ann.
      Neurol., 9 (1981) 131-141) to investigate sensorimotor and locomotor deficits in
      these animals during development and as adults. Sensorimotor deficits were
      examined by measuring the amount of time that the animals were able to remain on
      a rotating treadmill. Locomotor abnormalities were assessed by measuring
      apomorphine-induced rotational asymmetry. Following the neonatal ischemic-hypoxic
      episode, at 3-9 weeks of age, animals were not able to remain on the treadmill as
      long as their normal littermate controls. In addition, these animals demonstrated
      an abnormal, ipsiversive rotational asymmetry in response to systemic
      administration of apomorphine. When these animals reached adulthood, the degree
      of atrophy in specific regions of the damaged hemisphere was quantified using
      measurements of cross-sectional area. The mean cross-sectional area of the
      striatum was decreased by 29%, the sensorimotor cortex area by 26%, and the
      dorsal hippocampus cross-sectional area was approximately 6% of its normal size.
      These data suggest that this rodent model of neonatal ischemic-hypoxic brain
      injury results in cerebral atrophy and long-lasting sensorimotor and locomotor
      deficits. These particular behavioral tasks may be used in future studies to
      assess locomotor and sensorimotor deficits following neonatal ischemic-hypoxic
      brain injury.

PMID- 8864052
TI  - The differential haloperidol effect on the immobility response elicited by
      clamping, grasping, bandaging and inversion in guinea pig, hamster and rat.
AB  - The induction and modification by haloperidol of inhibitory responses, by 4
      inducing stimuli (inversion, clamping, bandaging and grasping) were studied and
      compared in guinea pig, hamster and rat. When undrugged, all 4 stimuli induced
      immobility responses in guinea pig; only clamping, bandaging and grasping, but
      not inversion, induced immobility responses (IR) in hamsters; only clamping and
      grasping, but not inversion and bandaging induced IR in rats. Haloperidol
      significantly potentiated the occurrence and duration of the IR by clamping,
      grasping and bandaging in rats. In hamsters haloperidol only potentiated the IR
      induced by bandaging, and in guinea pigs, haloperidol had no effect on IR
      produced by any of the stimuli. These findings suggest an inverse relationship
      between susceptibility to IR and the potentiation of IR by haloperidol.

PMID- 8864053
TI  - Recovery of function after neonatal ablation of the auditory cortex in rats
      (Rattus norvegicus).
AB  - Functional recovery following neonatal ablation of the auditory cortex was
      surveyed in 28 rats. Fourteen neonatal-lesioned rats had their temporal cortex
      lesioned on the date of birth (P1); 7 adult-lesioned rats had their auditory
      cortex lesioned at P60; and 7 rats served as controls. The training consisted of
      two phases using task with a Go/No Go procedure. The first task was to detect the
      presentation of a tone pulse. The second task was to discriminate the pulse rate
      of a tone pulse. Results showed that the achievements of neonatal-lesioned and
      control groups were comparable in both tasks. Adult-lesioned rats, however,
      failed to discriminate temporal patterns, although they could detect tone
      presentation as efficiently as the other two groups. These findings suggested
      that discrimination of temporal patterns could be a critical function of the
      auditory cortex and that brain injury in infancy was more compensated than the
      comparable damage in adulthood. Neurological plasticity was suggested in the
      recovery of function in our neonatal-lesioned animals.

PMID- 8864054
TI  - Neonatal hippocampal lesions induced hyperresponsiveness to amphetamine:
      behavioral and in vivo microdialysis studies.
AB  - The effect of neonatal hippocampal lesions on behavioral sensitivity to
      amphetamine (AMPH) and dopamine (DA) release in the nucleus accumbens (NAc) were
      examined. The ventral hippocampus was damaged bilaterally by ibotenic acid on
      postnatal day 7 (PD7). Spontaneous exploration and AMPH-stimulated locomotor
      activity were examined on postnatal day 35 (PD35) and day 56 (PD56).
      Extracellular DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA),
      and 5-hydroxyindoleacetic acid (5-HIAA) were sampled using in vivo microdialysis
      while simultaneously AMPH-stimulated locomotion was examined in freely moving
      rats on PD56. Spontaneous exploration increased in rats with hippocampal lesions
      relative to controls on PD56 but not PD35. AMPH (0, 0.187, 0.375, 0.75, 1.5, and
      3 mg/kg) enhanced locomotion dose-dependently in both control and lesioned
      groups. Locomotor activity was higher in lesioned rats than controls following
      AMPH at the dose of 0.75 mg/kg on PD35 and at the doses of 1.5 and 3.0 mg/kg on
      PD56. The basal level of DA in the NAc was not different between the hippocampal
      and control groups. AMPH (1.5 mg/kg) induced hyperlocomotion in lesioned rats
      relative to controls. DA release in the NAc for both groups was enhanced
      following injections of AMPH. However, neonatal hippocampal lesions had no
      further enhancement on AMPH-stimulated release of DA as compared to the control
      group. The levels of DOPAC and HVA in the NAc were altered by AMPH but not
      lesions. The level of 5-HIAA was not influenced by either lesions or AMPH. The
      results of neonatal lesion-induced hyperlocomotion suggest that an emergence of
      behavioral hyperresponsiveness to AMPH was dependent on an interaction of
      lesions, age of examination, and dose of the drug. A dissociation between the
      effect of AMPH on lesion-enhanced hyperlocomotion and a lack of a lesion-enhanced
      DA release in the NAc suggest that presynaptic release of DA had no major
      contribution to lesion-enhanced DA transmission in the mesolimbic DA system.

PMID- 8864055
TI  - The role of brain noradrenaline in cortical activation and behavior: a study of
      lesions of the locus coeruleus, medial thalamus and hippocampus-neocortex and of
      muscarinic blockade in the rat.
AB  - Local injection of 6-hydroxydopamine in the locus coeruleus resulted in a 90%
      depletion of noradrenaline (NA) in the cerebral cortex as assessed by high
      pressure liquid chromatography. This NA depletion had no effect on scopolamine
      resistant hippocampal rhythmical slow activity and only an occasional effect on
      scopolamine-resistant neocortical low voltage fast activity. However, NE
      depletion resulted in a slight deficit in a behavioral swim-to-platform test and
      increased the deficit produced on the test by systemic treatment with
      scopolamine. Large surgical lesions of the medial thalamus or hippocampal
      formation plus posterior neocortex greatly increased the behavioral deficit
      produced by scopolamine. It is concluded that ascending noradrenergic projections
      play only a modest and possibly indirect role in the control of electrocortical
      activation and that a number of different brain lesions increase the behavioral
      impairment produced by central muscarinic blockade.

PMID- 8864056
TI  - Acquisition of a runway motor learning task is impaired by a beta adrenergic
      antagonist in F344 rats.
AB  - Performance of rats on a motor learning paradigm that has been demonstrated to be
      dependent upon cerebellar norepinephrine (NE) was studied in male F344 rats
      treated with an alpha 1 antagonist (prazosin), an alpha 2 antagonist (yohimbine)
      or a beta noradrenergic antagonist (propranolol). The ability of propranolol
      treated rats (10 mg/kg i.p. 30 min prior to daily testing) to acquire proficiency
      on the novel motor task was impaired while prazosin-treated rats' (0.5 mg/kg i.p.
      30 min prior to daily testing) and yohimbine-treated rats' (1 mg/kg i.p. 30 min
      prior to daily testing) rates of acquisition of the novel motor task were not
      different from controls. In an attempt to distinguish between alterations in
      motor coordination and motor learning, additional tests of psychomotor
      performance were assessed for all groups of rats. These examinations included a
      walking test on 2.5 and 5 cm rods and speed of running on the motor task. The
      data indicate that drug-treated rats show no difference from controls on the
      above parameters. Some differences, however, were observed between propranolol
      and controls in the time spent in the goal box. Overall, the data are consistent
      with our hypothesis that the beta noradrenergic receptor is involved in the
      ability to acquire novel motor tasks.

PMID- 8864057
TI  - Effect of pimozide on self-stimulation threshold under a continuous and fixed
      interval schedule of reinforcement.
AB  - Rats implanted with a monopolar electrode in the medial mesencephalon and trained
      to press a lever to self-administer trains of stimulating pulses were tested
      under a continuous (CRF) and a fixed interval (FI-1s) schedule of reinforcement
      before and after systemic pimozide injection (0.35 mg/kg). As previously shown,
      this dose of pimozide caused reductions in maximal response rates and in the
      rewarding effectiveness of the stimulation. The magnitude of the attenuation in
      rewarding effectiveness was significantly greater under CRF than under FI
      conditions, an effect that can be attributed to the decrease in the number of
      earned rewards concomitant to a decrease in response rates. The present results
      show that the tighter control over reward density provided by the use of a FI
      schedule of reinforcement reduces the probability of artifactually measuring
      increases in reward thresholds following treatments that suppress response rates.

PMID- 8864058
TI  - Regulation of gene expression and transcription factor binding activity during
      cellular aging.
AB  - Human diploid fibroblasts (HDFs) undergo a limited number of population doublings
      in vitro and are widely used as a model of cellular aging. Despite growing
      evidence that cellular aging occurs as a result of altered gene expression,
      little is known about the activity of transcription factors that regulate gene
      expression in aging cells. Here we survey the relevant literature regarding
      altered gene expression and the role of transcription factors during cellular
      aging, focusing upon the serum response factor (SRF). SRF is hyperphosphorylated
      in senescent HDFs and fails to bind to the serum-response element in the c-fos
      promoter. Differential phosphorylation during replicative aging may contribute,
      at least in part, to the altered activity of SRF and possibly other transcription
      factors and to subsequent changes in the expression of serum-regulated genes in
      senescent HDFs.

PMID- 8864060
TI  - Replicative senescence, aging and growth-regulatory transcription factors.
AB  - Normal somatic cells invariably enter a state of permanent growth arrest and
      altered function after a finite number of divisions. This phenomenon is termed
      cellular or replicative senescence. Replicative senescence is thought to be a
      tumor-suppressive mechanism, and a contributing factor in aging. Three features
      distinguish senescent from presenescent cells: an irreversible block to cell
      proliferation, increased resistance to apoptotic death, and changes in
      differentiated functions. Senescence entails an altered pattern of gene
      expression, much of which is due to altered transcription. At least three growth
      regulatory transcriptional modulators are repressed in senescent cells: the c-fos
      component of the AP1 transcription factor, the Id1 and Id2 helix-loop-helix (HLH)
      proteins that negatively regulate basic HLH transcription factors, and the E2F-1
      component of the E2F transcription factor. Failure to express any one of these
      modulators is very likely sufficient to arrest cell proliferation. Loss of these
      modulators may also explain many of the functional changes shown by senescent
      cells. In the case of c-fos repression, the resulting decline in AP-1 activity
      may be exacerbated by an altered ratio of AP-1 components to a protein known as
      QM or Jif. QM interacts with the c-jun component of AP-1 and suppresses AP-1
      activity. We cloned QM from a senescent fibroblast cDNA library, and found that
      it was neither cell cycle- nor senescence-regulated. However, QM suppressed the
      growth of murine and human fibroblasts when overexpressed. Thus, an altered
      balance between positive factors (e.g., AP-1 components) and negative factors
      (e.g., QM) may lead to the growth arrest, as well as the changes in
      differentiated gene expression, that are a hallmark of senescent cells.

PMID- 8864061
TI  - Cell cycle- and age-dependent transcriptional regulation of human thymidine
      kinase gene: the role of NF-Y in the CBP/tk binding complex.
AB  - Expression of thymidine kinase gene in normal human diploid cells is both cell
      cycle- and age-dependent and appears to be transcriptionally regulated. Strong
      DNA protein binding with a 28-bp fragment (-91/-64) that contains the distal
      inverted CCAAT box is observed in serum-stimulated young (low population doubling
      level) IMR-90 cells but not in senescent cells. This cell cycle- and age
      dependent binding factor was termed CBP/ tk, indicating CCAAT binding protein for
      the thymidine kinase gene. Based on immunoshift assay and purification, it has
      been suggested that CBP/tk is equivalent to NF-Y, previously identified as the
      binding protein for the Y box within E alpha gene promoter. In this study, we
      examined the mRNA level and protein amount of NF-Y, proteins in young and old IMR
      90 cells during serum stimulation by Northern and Western blot blot analyses. In
      addition, we compared (1) the turnover rate of NF-Y in IMR-90 cells with that of
      CBP/tk binding activity and (2) the levels of NF-Y and CBP/tk in normal and
      cancer cells. Both NF-YA and NF-YB were constitutively expressed at mRNA level in
      IMR-90 cells. However, expression of NF-YA, and to a lesser degree, NF-YB, at the
      protein level were clearly age-dependent. The half-life of NF-YA and NF-YB were,
      respectively, 4- and > 10-fold longer than that of CBP/tk binding activity in IMR
      90 cells. In addition, we found that the amount of NF-Y did not correlate with
      the overexpression of CBP/tk binding activity in HeLa cells. Taken together, our
      results suggested that although CBP/tk may contain NF-YA or related proteins, NF
      A and NF-YB alone may not account for all the characteristics of CBP/tk observed
      in normal and transformed human cells.

PMID- 8864059
TI  - The tumour suppressor gene p53 as a regulator of proliferative life-span and
      tumour progression.
AB  - This review develops the concept of p53 as a transcription factor mediating
      growth arrest or cell death in response to long-term (senescence-related) as well
      as acute (DNA damage) signals. Evidence is presented to support the importance of
      both functions in tumour development. The role of p53 in senescence is discussed
      in the context of the telomere theory and in relation to its more established
      function as a 'guardian of the genome'. Finally, data indicating important tissue
      specific differences in the control of proliferative life-span by p53 are
      reviewed, together with potential clinical implications.

PMID- 8864062
TI  - Role of transcription factors in the age-dependent regulation of the androgen
      receptor gene in rat liver.
AB  - Androgen receptor (AR) is a ligand-activated transcription factor involved in
      mediating male reproductive functions. The high expression of the AR gene in
      target tissues of young-adult animals is generally followed by an age-dependent
      decline during the postreproductive life. The liver of male rats shows about a 50
      to 100-fold decline in androgen sensitivity during old age due to a concomitant
      decline of the AR gene expression. This decline corresponds to changes in the
      nuclear level of several transcription factors that bind to the AR gene promoter.
      The positively acting factors that control the AR gene and undergo an age
      dependent decline include the age-dependent transcription factor (ADF), Sp1 and
      the serum response factor (SRF). Nuclear factor kappa B, which functions as a
      negative regulator of the AR promoter, undergoes about a 10-fold increase during
      the age-dependent loss of the hepatic androgen sensitivity. Additionally, AP3,
      which can potentially function as a regulator of the AR gene, shows a marked
      increase during old age. Thus, a coordinated interaction among a number of
      positive and negative regulators appears to guide the downregulation of the AR
      gene during aging.

PMID- 8864063
TI  - Heat shock response, heat shock transcription factor and cell aging.
AB  - A characteristic feature of aging is a progressive impairment in the ability to
      adapt to environmental challenges. The purpose of this article is to review the
      evidence of an attenuated response to heat and physiological stresses in a number
      of mammalian aging model systems, including the human diploid fibroblasts in
      culture, whole animals and animal-derived cells and cell cultures, as well as
      peripheral blood mononuclear cells obtained from human donors. Analyses of the
      regulation and function of heat shock factor 1 (HSF1), a transcription factor
      that mediates the response to heat shock, showed that while the relative
      abundance of both the hsf1 transcript and the HSF1 protein did not change as a
      function of age, the responsiveness of HSF1 to heat-induced activation, as
      measured by its trimerization and ability to bind to the heat shock element
      consensus sequence, was inversely related to the age of the cells used. Given the
      fundamentally important role of heat shock proteins (HSPs) in many aspects of
      protein homeostasis and signal transduction it seems likely that the inability,
      or compromised ability, of aging cells and organisms to activate HSF1 and produce
      HSPs in response to stress would contribute to the well-known increase in
      morbidity and mortality of the aged when challenged.

PMID- 8864072
TI  - Emergency surgery in hematologic patients.
AB  - Patients at risk for clinically significant bleeding and who require urgent or
      emergent surgical procedures are encountered. Usually local causes are
      responsible, but a generalized hematologic defect may be uncovered. Quickly and
      effectively distinguishing the cause may be critical to rapid treatment and
      survival. A careful history, appropriate use of laboratory tests (e.g., partial
      thromboplastin time, prothrombin time, and platelet count), and knowledge of
      possible causes are key to prompt diagnosis and treatment. Bleeding from multiple
      sites, spontaneous bleeding, or unexpectedly severe bleeding suggests a systemic
      process. Immunocompromised or suppressed patients or systemically ill patients
      with chronic hepatic renal, lymphatic, and hematologic disorders are seen with
      urgent surgical problems. The key is rapid diagnosis and effective systemic and
      local therapy to counter the problem. The syndrome of diffuse "medical bleeding"
      frequently confronts the surgeon treating a patient who has received transfusions
      of more than 1.5 times blood volume. The coagulation defect is almost always
      associated with hypothermia and acidosis. Treatment consists in control of large
      vessel bleeding by appropriate surgical techniques, blunt packing, and tamponade
      of diffuse bleeding, rapid rewarming of the patient, and adequate resuscitation
      for shock. Transfusion of platelets and fresh frozen plasma is empiric initially
      and subsequently guided by the clinical and laboratory coagulation profiles of
      the patient.

PMID- 8864073
TI  - What is new in the prophylaxis and treatment of venous thromboembolism?
AB  - Deep venous thrombosis continues to be a frequent complication of surgery and
      trauma. The topic is controversial with regard to diagnosis, indication for
      prophylaxis, and suitable methods for prophylaxis and therapy. We review some of
      the highlights of the extensive literature in this field during the last few
      years. Particular emphasis is given to new trends in diagnostic methods, newly
      discovered genetic factors for thrombophilia, and the use of heparins for
      prophylaxis and therapy of thromboembolic disease.

PMID- 8864074
TI  - Surgical strategy for management of deep venous thrombosis of the lower
      extremities.
AB  - Clinical experience proves that there is a considerable group of patients with
      acute proximal deep vein thrombosis (DVT) of the legs who have absolute or
      relative contraindications to anticoagulants or thrombolytic agents but require
      immediate medical treatment. The aim here is to present our strategy for
      qualifying patients for venous thrombectomy and the technique of the operation in
      patients with acute iliofemoral DVT. A total of 268 patients with DVT were
      evaluated. A proximal thrombosis was diagnosed in 225 cases (84%), and acute
      thrombosis was found in 126 (56%) of these 225 patients. Venous thrombectomy with
      temporary arteriovenous fistula was performed in 30 patients. In the remaining
      patients initial treatment included heparin, acenocumarol, or both in 61,
      thrombolytic agents in 26, and other therapy in 9 cases. Three patients died
      during the early postoperative period. Minor nonhemorrhagic complications were
      observed in four operated patients. One patient developed wound hematoma. In all
      but three operated cases the patency of the iliac and femoral veins with leg
      swelling in 16 patients was observed 1 year after fistula closure. There were no
      episodes of rethrombosis during this period. None of the thrombectomized patient
      had leg ulcers. Eight patients were free of clinical symptoms related to DVT. We
      believe that venous thrombectomy provides a good chance for satisfactory
      restoration of venous outflow in patients with acute proximal DVT. Venous
      thrombectomy with temporary arteriovenous fistula represents the treatment of
      choice in patients with acute, proximal DVT and with contraindications to heparin
      treatment.

PMID- 8864075
TI  - Role of splenectomy in hematologic disorders.
AB  - There has been an increase in the indications for splenectomy for hematologic
      diseases. It is a consequence of expanding the list of disorders and liberalizing
      the indications for splenectomy for many diseases. Hereditary spherocytosis is
      the most frequently encountered congenital anemia for which splenectomy is
      curative. Splenectomy is generally advised for warm antibody acquired hemolytic
      anemia if conventional medical therapy fails. Idiopathic thrombocytopenic purpura
      (ITP) remains the most common hematologic disorder for which splenectomy is
      therapeutic. A variety of thrombocytopenias are improved by splenectomy. The
      myeloproliferative disorders constitute a spectrum of disease potentially
      improved by splenectomy, but preoperative management should be modified in this
      group. Splenectomy in patients with chronic leukemias and lymphomas are often
      palliative and facilitate chemotherapy. There are no specific requirements
      preoperatively other than the administration of pneumococcal and Hemophilus
      influenzae vaccines. Platelets are not administered to patients with ITP. An
      integral part of the procedure is the search for accessory spleens. The
      postoperative complication of overwhelming postsplenectomy sepsis must be
      considered; it occurs more frequently in association with specific basic diseases
      and can be obviated by appropriate treatment.

PMID- 8864076
TI  - Hematologic problems and organ transplantation.
AB  - Disturbances in blood coagulation profiles combined with intraoperative technical
      problems may lead to hemorrhage and significant blood loss. During the
      postoperative period hematologic changes may result from the use of
      immunosuppressive drugs, so careful monitoring and review are essential parts of
      management. The two major aspects of hematologic change are reviewed.

PMID- 8864077
TI  - Endoscopic injection treatment of gastrointestinal bleeding in hemophiliacs.
AB  - The aims of this prospective study were to determine the patterns of
      gastrointestinal (GI) bleeding in hemophiliacs and to assess the hemostatic
      effect of injection therapy with alcohol. During a 5-year period (1990-1994) 89
      hemophiliacs were admitted to our department with acute GI bleeding. Among these
      patients duodenal ulcer was found endoscopically to be the most common (42.7%)
      cause of hemorrhage; gastric ulcer was the source of the bleeding in only three
      patients (3.4%). A group of 46 patients met the criteria of active or recent
      bleeding and underwent injection therapy with alcohol. The injected bleeding
      lesions were duodenal ulcer in 32 patients, duodenal erosion in 2, gastric ulcer
      in 3, and other gastric lesions (Mallory-Weiss tear, Dieulafoy lesion, stomal
      ulcer, erosions) in 9 patients. Initial hemostasis was achieved in 100% and
      permanent hemostasis in 82.6%. Rebleeding was observed in eight patients (17.4%),
      with five of them successfully treated by reinjections. Three patients (6.5%)
      required emergency surgery. The mortality rate in the group of injected patients
      was 2.2%. One patient died of stroke on day 10 after partial gastrectomy. All
      injected patients were given replacement therapy with factor VIII or IX for 2
      days (29 patients) or 7 to 14 days (17 patients). Analysis of the hemostatic
      effect achieved in these two subgroups indicate that short-term replacement
      therapy (2 days) may be sufficient to ensure adequate hemostasis in hemophiliacs.
      The results of the present study indicate that injection therapy with alcohol is
      an effective, safe, proved method to control GI bleeding in hemophiliacs.

PMID- 8864078
TI  - Surgery in hemophilia A patients with factor VIII inhibitor: 10-year experience.
AB  - Patients with hemophilia A and circulating anticoagulant (factor VIII inhibitor)
      present a difficult, even unsolvable problem, particularly if they require
      surgical treatment and the inhibitor titer is high. During the 1986-1995 period
      29 surgical procedures on inhibitor hemophilia A patients were performed in our
      center. Each of the cases had an individual character, and all demanded special
      clinical treatment. Based on this experience we present the possibilities of
      hemostasis maintenance during the perioperative period with high doses of human
      or porcine factor VIII, aPCC, plasmapheresis, and extracorporeal antibody
      adsorption to protein A-Sepharose. In some patients hemostasis maintenance
      requires combined treatment. To induce immunotolerance in patients with inhibitor
      is the gold standard treatment because it is then possible to achieve proper
      hemostasis after factor VIII infusion. Various methods of immunotolerance
      induction have been discussed and compared with our experience with
      immunotolerance induction in 11 patients with small factor VIII doses (25 IU/kg
      twice a week) and the modified Malmo protocol in 15 patients.

PMID- 8864079
TI  - Safe hemoglobin or hematocrit levels in surgical patients.
AB  - The terminology and fundamental aspects of the delivery, consumption, and
      deficits of oxygen are recalled. In chronic and acute, nonseptic states, red
      blood cell (RBC) transfusion is capable of increasing oxygen consumption (VO2).
      In acute septic states, the response of VO2 to RBC transfusion is variable and
      unpredictable, but attempts to increase oxygen delivery (DO2) should be made if
      the clinical picture raises the suspicion of a potentially lethal oxygen deficit.
      Therapeutic interventions raising the cardiac index to "supranormal" values in
      critically ill patients improve their chances of survival; and maintenance of
      hemoglobin or hematocrit values around 11 g/dl or 33%, respectively, is one part
      of such interventions. Opinions differ on the general tolerance of anemia, as
      witnessed by postulated "critical levels" of the hemoglobin concentration between
      approximately 11 and 4 to 5 g/dl or hematocrit values between 33% and 12% to 15%,
      respectively. The common denominator underlying these vastly different opinions
      is the variable behavior of several "non-Hb variables," which influence the
      venous oxygen tensions apart from the hemoglobin or hematocrit. Abnormalities of
      these non-Hb variables-typically encountered in the critically ill-increase the
      dependence of patients on hemoglobin or hematocrit levels that suffice to protect
      them against an oxygen deficit. For this reason, the "critical" hemoglobin or
      hematocrit is an individual value, and a generally valid "transfusion trigger"
      does not exist. Finally, the entity now known as silent myocardial ischemia (SMI)
      is a decisive factor for the tolerance of anemia. Solid clinical evidence is now
      available to support the concept that patients over age 40 should not, as an
      elective procedure, be subjected to levels < 10 g/dl or < 30%, respectively,
      without prior exclusion of SMI by appropriate investigations.

PMID- 8864080
TI  - Benefits and risks of blood transfusion in surgical patients.
AB  - This article attempts to put into a risk-related perspective modern red blood
      cell (RBC) transfusion therapy. When making the decision to transfuse, RBCs or
      blood products, it is important to weigh the risks and benefits of the proposed
      therapy. It is equally important to evaluate the risk of not transfusing and the
      morbidity and mortality associated with that decision. After nearly a century of
      use, RBC transfusions continue to be associated with a variety of risks. Although
      the initial risks of mismatch and infectious disease transmission are ever
      decreasing, new risk considerations, particularly immunosuppression, are being
      uncovered. Because of the nearly universal worldwide fear of transfusion-related
      transmission of infectious disease a more conservative transfusion policy has
      generally taken hold. Transfusion avoidance philosophies and then increased use
      of autologous RBCs have become commonplace. This article puts a decision-oriented
      slant on the risk and benefit of transfusion therapy. The issues behind the
      inability to discern a defined benefit as well as a commentary on the newly
      perceived risks is provided. Overall, when increased oxygen delivery is required,
      the addition of RBCs has an apparent survival benefit in some specific patients.
      In these patients the risk of transfusion-related complication is minimized
      compared to the mortality outcome. For cancer and trauma patients, if transfusion
      is immunosuppressive and therefore detrimental, alternatives must be considered.
      The newest question is whether the act of transfusion, independent of the form,
      allogeneic or autologous, is of itself immunosuppressive.

PMID- 8864081
TI  - Recombinant blood components: clinical administration today and tomorrow.
AB  - Improvements in the technology of whole blood fractionation have resulted in the
      development of many subfractions that allow more specific management of clotting
      deficiencies, such as the hemophilias. Infective disasters have occurred in
      recent years, which has led to concern regarding the use of human blood
      components. There has been great interest in the search for alternatives, such as
      synthetic volume expanders, antifibrinolytic drugs, and hormones to stimulate
      bone marrow production. Recombinant technology has developed rapidly over the
      past 15 years, and several products are now available for use, including
      recombinant factor VIII and recombinant factor VIIa for the treatment of
      hemophilia and recombinant erythropoietin to stimulate red blood cell production.
      As these recombinant proteins are complex, they require mammalian cell lines as
      their substrate. Recombinant processes have the potential to produce sufficient
      quantities of these products for the treatment of patients around the world
      independent of a human plasma source. The introduction of all of the new
      recombinant products has been done in an orderly fashion through clinical trials.
      Erythropoietin was extensively reviewed initially for its effect in chronic renal
      failure patients and appears to have other applications. Recombinant factor VIII
      has now become a mainstay of treatment for many patients with hemophilia A, and
      recombinant factor VIIa has a major role to play in the management of patients
      with inhibitors to factors VIII and IX. We anticipate the availability of other
      recombinant blood proteins soon.

PMID- 8864082
TI  - Clinical development of human polymerized hemoglobin as a blood substitute.
AB  - Although the efficacy of hemoglobin-based oxygen carriers was established more
      than 60 years ago, all prior clinical trials have demonstrated significant
      toxicity characterized by renal dysfunction, gastrointestinal distress, and
      systemic vasoconstriction. The mechanisms of these toxicities now appear to be
      understood. Tetrameric forms of the hemoglobin molecule extravasate from the
      circulation and interact with endothelium-derived relaxing factor, leading to
      unopposed vasoconstriction. Although numerous efforts are under way to chemically
      modify the native tetramer, it is likely that all tetrameric forms of the
      hemoglobin molecule will continue to extravasate. We have focused on developing a
      polymerized form of hemoglobin that is virtually free of unreacted tetramer. The
      development and characterization of this polymerized pyridoxylated hemoglobin
      solution (Poly SFH-P) is described. Clinical trials have been completed
      successfully in volunteers and are now under way to assess the safety and
      efficacy of Poly SFH-P as a clinically useful red blood cell substitute for
      treatment of acute blood loss in the setting of trauma and surgery.

PMID- 8864083
TI  - Hemodilution in clinical surgery: state of the art 1996.
AB  - Acute normovolemic hemodilution entails removal of blood from a patient either
      immediately before or shortly after induction of anesthesia and simultaneous
      replacement with cell-free fluid. Nowadays, because of their predictable volume
      effects, the synthetic colloids (6% dextran 60/70, 6% hydroxyethyl starch
      200,000) are preferred as volume substitutes; albumin should be avoided because
      of its high cost. Hemodilution has experienced a renaissance in recent years,
      mainly due to the evolving discussion of legal aspects, immunologic changes,
      viral infections, and a potentially higher cancer recurrence rate associated with
      the transfusion of homologous blood. Hemodilution should be considered for
      elective surgical patients free of contraindications and presenting with an
      initial hemoglobin concentration >/= 12 g/dl and an anticipated blood loss of >/=
      1500 ml. The efficacy of this method (judged by the need to give homologous blood
      transfusion) depends on the preoperative (initial) hematocrit, the target
      hematocrit (to which hemodilution is performed), and the preset intra- and
      postoperative transfusion trigger. In the past, data from clinical trials showed
      that in healthy subjects a target hematocrit of 20% to 25% (hemoglobin 7.0-8. 0
      g/dl) is feasible and safe for the patient. The lower the target hematocrit
      accepted, the more extensive is the monitoring required: Intraoperative target
      hemoglobin concentrations of 5.0 g/dl and less have been tolerated by surgical
      patients without adverse effects. The safety and efficacy of acute normovolemic
      hemodilution in terms of reducing homologous blood transfusion requirements has
      been demonstrated in various clinical studies. Hemodilution therefore is regarded
      an integral part of programs aimed at reducing the need for homologous blood and
      can thus be successfully combined with preoperative autologous blood deposition,
      intraoperative blood salvage, and carefully adjusted surgical techniques.
      Hemodilution is feasible and relatively cost-effective, and it minimizes adverse
      effects associated with transfusion of homologous blood, particularly
      transmission of viral diseases, immunosuppression, and infectious complications.

PMID- 8864084
TI  - Laparoscopic surgery and the third world.

PMID- 8864085
TI  - Gastrointestinal problems in the immunocompromised host. A review for surgeons.
AB  - As the immunocompromised patient population grows, the gastrointestinal surgeon
      is increasingly called upon to make complex diagnostic and therapeutic decisions.
      The surgeon should first identify the patient as immunocompromised and then
      categorize the probable degree of immunocompromise as mild, moderate, or severe.
      Mildly immunocompromised patients tend to present late and with minimal symptoms,
      but the disease entities are the same ones seen in the general population.
      Moderately and severely immunocompromised patients may also develop the usual
      surgical problems, but the differential diagnosis is expanded to include
      complications of the immunocompromised state or complications of the underlying
      problem which caused the immune compromise. The expanded differential diagnosis
      includes infections with atypical organisms, opportunistic neoplasms, neutropenic
      enterocolitis, complications of medications, and forms of biliary tract disease
      not seen in the general population. Advances in oncology, transplantation, and
      the treatment of AIDS, have extended the life expectancy of these patients and
      increased the immunocompromised population. Prompt appropriate operative therapy
      may be lifesaving when surgical complications develop.

PMID- 8864086
TI  - A microprocessor-controlled psychomotor tester for minimal access surgery.
AB  - BACKGROUND: There is little reported information on psychomotor performance in
      relation to minimal access surgery (MAS). METHODS: A microprocessor-controlled
      endoscopic psychomotor tester (the Dundee Endoscopic Psychomotor Tester-DEPT) has
      been developed to evaluate psychomotor aspects of MAS. Experiments were conducted
      on 20 medical undergraduates to evaluate accuracy and reliability of the tester.
      RESULTS: The study demonstrated a significant difference between subjects (p <
      0.01). It also identified three individuals who enacted 16, 22, and 40 errors
      while the majority (85%) sustained less errors with a median of 4.5. CONCLUSIONS:
      DEPT provides a standard, reproducible, objective real-time scoring system. It
      identifies individuals who cannot adjust to endoscopic viewing and therefore
      manipulate from endoscopic images.

PMID- 8864087
TI  - Management of malignant biliary stricture with self-expanding metallic stent.
AB  - BACKGROUND: Self-expanding metallic mesh stents are designed to remain patent
      longer than polyethylene (PE) stents, which generally clog in 3 to 4 months.
      Though more expensive, metal stents may therefore be a better choice for
      malignant strictures. METHODS: From January 1991 to October 1995, we performed
      ERCP in 212 patients with malignant or benign strictures, and 34 ultimately had
      insertion of a metallic stent. These stents were placed by the percutaneous
      transhepatic route in 17 patients and endoscopically in 17. RESULTS: Metallic
      stent insertion was successful in each case and relieved the preoperative
      jaundice and cholangitis. There were no procedure-related deaths; complications
      were pancreatitis (one) and hemorrhage (one). Overall stent patency was 6.2
      months. Three of 34 stents occluded due to tumor ingrowth at 3, 4.5, and 8 months
      and were treated by placing a new PE stent through the blocked metal stent. The
      remaining 31 stents remained patent until patient death (n = 15, mean survival =
      4.9 months) or are still open (n = 16, mean patency = 12.2 months). CONCLUSIONS:
      Self-expanding metal stents provide effective palliation of malignant biliary
      strictures and should be considered an alternative to open surgery. Metal stents
      remain patent much longer than PE stents and usually a single session of metal
      stenting can palliate biliary obstruction for life.

PMID- 8864088
TI  - Alterations in hemodynamics and left ventricular contractility during carbon
      dioxide pneumoperitoneum.
AB  - BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum has been shown to adversely
      affect hemodynamics in patients. This study specifically examines the potential
      contribution of altered left ventricular contractility (LVC) to hemodynamic
      changes observed during CO2 pneumoperitoneum. METHODS: In a canine model, LV
      volumes, LV pressure, and intrathoracic and central venous pressures were
      recorded both at basal intra-abdominal pressure (IAP) and after CO2 insufflation
      to produce IAPs of 5-25 mmHg. RESULTS: At IAPs greater than 15 mmHg, cardiac
      output and LV end-diastolic volume decreased. Mean arterial pressure and heart
      rate were unchanged. LVC, quantified using the linear Frank-Starling
      relationship, was not affected by increases in IAP. CONCLUSIONS: This study is
      the first to quantify LVC during CO2 pneumoperitoneum and demonstrates no changes
      in contractility over IAPs from 5 to 25 mmHg. In the dog model, any hemodynamic
      alterations induced by CO2 pneumoperitoneum are secondary to altered LV preload
      and not alterations in contractility or LV afterload.

PMID- 8864089
TI  - Mechanisms and avoidance of esophageal perforation by anesthesia personnel during
      laparoscopic foregut surgery.
AB  - BACKGROUND: This study retrospectively assesses the mechanisms of 13 esophageal
      or gastric injuries resulting from dilator or nasogastric tube placement during
      laparoscopic foregut surgery and is intended to assist in determining methods of
      prevention. METHODS: Information regarding esophageal or gastric injury during
      laparoscopic foregut surgery was obtained from six experienced laparoscopic
      surgeons. The specific mechanisms of injury were determined by discussion with
      the operating surgeon and review of the operative reports. RESULTS: Eleven cases
      of esophageal or gastric perforation occurred during bougie insertion and two
      perforations occurred secondary to nasogastric tube placement during Nissen
      fundoplication or Heller myotomy. Five perforations required conversion to open
      operation for repair including two delayed thoracotomies. The 13 injuries
      occurred during the performance of 1,620 laparoscopic foregut operations for an
      overall incidence of 0.8%. CONCLUSION: Foregut injury resulting from
      esophagogastric intubation during laparoscopic surgery is more common than
      expected. Risk factors include esophageal anatomy, intrinsic pathologic changes
      of the esophagus, and inexperience. Prevention must focus on close communication
      between the surgeon and anesthesiologist and safe techniques of dilator
      insertion.

PMID- 8864090
TI  - An assessment of pain and return to normal activity. Laparoscopic herniorrhaphy
      vs open tension-free Lichtenstein repair.
AB  - BACKGROUND: Laparoscopic herniorrhaphy is controversial and deserves critical
      evaluation. METHODS: In a randomized prospective study transabdominal
      preperitoneal laparoscopic herniorrhaphy (n = 24) was compared in patients to the
      tension-free Lichtenstein repair (n = 29) utilizing validated and reliable pain
      and activity assessment tools. The Sickness Impact Profile (SIP) was used to
      compare preoperative normal activity to postoperative activity. A Pain-O-Meter
      (visual analogue scale plus affective and sensory pain descriptors) assessed
      intensity of pain. The total pain assessment score and SIP were compared across
      time (postoperative day 1-42). Analgesic medication was used as a covariate.
      RESULTS: The total pain score was less for laparoscopic herniorrhaphy but this
      did not reach statistical significance. Similarly, the SIP showed modest
      improvement for laparoscopic herniorrhaphy. No differences between groups were
      noted for morphine equivalents of administered analgesics or length of
      hospitalization. CONCLUSION: Further investigation of laparoscopic herniorrhaphy
      is warranted.

PMID- 8864091
TI  - A comparison of open vs laparoscopic adrenalectomy.
AB  - BACKGROUND: To compare the outcome of patients who underwent laparoscopic
      transabdominal adrenalectomy (LA) with those who had open adrenalectomy (OA).
      METHODS: A retrospective review of consecutive adrenalectomies performed by a
      single surgical team at a university hospital. Outcome measurements were
      operative time, operative blood loss, procedure-related complications,
      postoperative stay, and return to regular activity. RESULTS: Twenty-nine
      adrenalectomies were done in 23 patients during a 54-month period. There were 12
      OAs performed in nine patients and 17 LAs were done in 14 patients. Both groups
      were similar in their demographics and their indications for operation. All
      attempted LAs were successfully completed. The mean operative time was longer for
      LA than for OA (289 vs 201 min; p = 0.042). Resumption of oral intake (1.0 vs 3.0
      days; p = 0.002), postoperative hospital stay (3.0 vs 7.9 days; p = 0.002), and
      return to regular activity (8.9 vs 14.6 days; p = 0.002) were significantly
      shorter after LA than after OA. There were no postoperative deaths and there was
      no difference in operative blood loss between the two groups. Procedure-related
      complications occurred in three patients having LA and in five patients having
      OA. CONCLUSIONS: Patients having LA had longer operative procedures but shorter
      hospital stays and faster return to normal activity than patients having OA.
      Procedure-related complications for LA were due to bleeding into the
      retroperitoneum or abdominal wall. Significant postoperative cardiac and
      respiratory complications occurred only in the OA group.

PMID- 8864092
TI  - Laparoscopic splenectomy for ITP. The gold standard.
AB  - BACKGROUND: A comparison of safety, efficacy, and cost of laparoscopic
      splenectomy (LS) vs open splenectomy (OS) for idiopathic thrombocytopenic purpura
      (ITP) was performed. METHODS: The records of 49 consecutive patients who
      underwent splenectomy for ITP (31 LS and 18 OS) at a large metropolitan teaching
      hospital between 3/91 and 8/95 were reviewed. Morbidity, mortality, hospital
      stay, operative time, blood loss, time to oral fluid intake, direct costs, and
      operating room (OR) costs were analyzed. RESULTS: Age, sex, comorbidity, and
      spleen size were similar in both groups. LS was successful in 94% of patients in
      whom it was attempted. Operative times showed a learning curve for LS, with
      average times for the last ten cases (94 +/- 35 min) significantly shorter than
      for the first ten (p = 0.01) and also shorter than for OS (103 +/- 45 min).
      Postsurgical hospital stay was 2.9 +/- 1.3 days for LS and 6.9 +/- 3. 0 days for
      OS (p < 0.001). Patients tolerated an oral diet 1.2 +/- 0. 5 days after LS and
      3.2 + 0.7 days after OS (p < 0.001). Direct hospital cost was $5,509 +/- 3,636
      for LS and $9,031 +/- 12,752 for OS. In the LS group, six patients (21%) had
      accessory spleens identified and removed, compared with two patients (11%) in the
      OS group. Platelet counts did not respond in two (7%) patients in the LS group,
      but no accessory spleens were identified by nuclear scan. One major complication
      occurred in the LS group. There were no cases of splenosis or mortality in either
      group. CONCLUSIONS: LS is a safe and effective treatment for ITP, with
      significantly shorter postoperative hospital stay than OS.

PMID- 8864094
TI  - Successfully establishing laparoscopic surgery programs in developing countries.
      Clinical results and lessons learned.
AB  - BACKGROUND: Laparoscopic surgery has not been widely established in developing
      countries due to the lack of access to training and lack of money. We describe
      our experience using on-site training programs to efficiently teach and propagate
      laparoscopic surgery in Leon, Nicaragua; La Paz, Bolivia; and Santa Cruz,
      Bolivia. METHODS: A group of well-trained and motivated local surgeons was
      identified in each country as the initial target for teaching. Participants were
      taught basic and advanced laparoscopic surgery during on-site didactics, animal
      laboratories, and proctoring sessions. Follow-up courses were held until the
      target group of surgeons was capable of independently teaching and supervising
      laparoscopic surgery among other surgeons in each country. RESULTS: Multiple
      technical and logistic difficulties were encountered. In Leon, Nicaragua, and La
      Paz, Bolivia, a total of eight surgeons were fully trained and proctored in
      laparoscopic cholecystectomy. In La Paz and Santa Cruz, Bolivia, a total of seven
      surgeons were instructed in advanced laparoscopic procedures. To date, over 180
      patients have undergone laparoscopic cholecystectomy or advanced procedures with
      a morbidity similar to that reported in literature series in the United States.
      CONCLUSIONS: Our experience demonstrates that in spite of numerous limitations,
      basic and laparoscopic surgery can be efficiently and safely taught in developing
      countries. Many lessons were learned in how to safely and efficiently use
      laparoscopic equipment and instruments within strict financial constraints.

PMID- 8864093
TI  - Immediately preoperative laparoscopic staging for gastric cancer.
AB  - BACKGROUND: This ongoing study is a prospective evaluation of immediately
      preoperative video-laparoscopy compared to ultrasound/computed tomography (US/CT)
      staging for gastric cancer. An analysis of the first 70 cases is reported.
      METHODS: TNM staging is used to compare the US/CT findings and the laparoscopic
      findings with the gold standard for pathologic findings in resected specimens.
      RESULTS: In our series 47 out of 70 cases are locally advanced cancers (stages
      III and IV): In this subset the predictive value of laparoscopic staging is
      86.4%. Laparoscopy shows an overall staging accuracy of 68.6%, compared to 32.8%
      for US/CT. The difference is statistically significant as regards the T factor
      (T3: 69.7% vs 12. 1%, p < 0.002; T4: 84.2% vs 42.1%, p < 0.05); as regards the M
      factor, laparoscopy appears the most specific method for detecting peritoneal
      seeding. CONCLUSIONS: This procedure plays a crucial role in determining the
      resectability of the tumor, thus avoiding unnecessary laparotomies. A meticulous
      staging becomes mandatory when applying modem treatment options (e.g., neo
      adjuvant chemotherapy) to locally advanced cancers; in this context the use of
      staging laparoscopy will have a relevant impact on future treatment.

PMID- 8864095
TI  - Estimated costs of biliary tract complications in laparoscopic cholecystectomy
      based upon Medicare cost/charge ratios. A case-control study.
AB  - BACKGROUND: Costs of laparoscopic cholecystectomy (LC)-associated biliary tract
      complications are poorly documented. METHODS: A retrospective, case-controlled
      study attempted to define costs in an institution-specific manner, as compared to
      a group of patients who underwent an uncomplicated LC at the same institution.
      Costs were estimated by obtaining actual hospital billing charges and multiplying
      them by each hospital's specific Medicare cost-to-charge ratio (MCCR). This is
      considered a reasonable estimate of cost. The MCCR is calculated annually and is
      the hospital's actual cost estimate divided by what it charges. RESULTS: Twelve
      complications consisting of six common bile duct transection/excisions (CBDTE),
      one CBD leak/stricture (CBDLS), and five cystic duct leaks (CDL) were identified
      and matched to a control group (having an uncomplicated LC) for age, sex, and
      institution where the LC had been completed. Mean cost for CBDTE was $9,061 +/-
      $5,112 vs $2,689 +/- $1,469 for controls (p = 0.015), and $6,937 +/- $3,317 for
      CDL vs the controls cost of $1,343 +/- $417 (p = 0.006). The single CBDLS injury
      cost $5,804 vs $3,611 for the control. While the costs of these complications are
      statistically significantly greater than the controls, they are dramatically less
      than the costs reported in the literature for these problems ($30,000-$300,000).
      CONCLUSIONS: Costs of LC-associated biliary tract complications, as calculated
      using MCCR multiplied by hospital charges, for each complication type were
      statistically significantly higher than for the control groups. Although more
      expensive than the controls, these complications do not appear to be as costly as
      has been reported in the past.

PMID- 8864096
TI  - Laparoscopic percutaneous jejunostomy for long term enteral access.
AB  - BACKGROUND: Patients suffering from upper gastrointestinal pathology may require
      jejunal feeding for adequate nutrition. A laparoscopically guided percutaneous
      jejunostomy offers a minimally invasive means of obtaining such feeding access.
      METHODS: Laparoscopic jejunostomy was performed in 32 patients. The most common
      indications were gastroparesis (n = 16), neurological deficits (n = 7), and
      proximal obstruction (n = 5). The proximal jejunum was affixed to the abdominal
      wall using intracorporeal and extracorporeal transabdominal sutures, allowing
      safe insertion of an 18-Fr Silastic dual-lumen tube. RESULTS: Laparoscopic
      jejunostomy was successfully completed for 28 patients; the procedure was
      converted to an open operation in four cases. Three of these four were among 14
      patients undergoing the procedure who had a history of previous abdominal
      surgery. Major complications were observed in seven patients, including one
      reoperation and one death from aspiration pneumonia. Tube feeding was
      accomplished in all patients; progression to full enteral feeding proceeded
      without interruption in 20 patients. CONCLUSION: Laparoscopic jejunostomy can be
      performed with relative safety. Morbidity, though high, is usually related to
      preexisting disease. Previous abdominal surgery is not necessarily a
      contraindication to laparoscopic jejunostomy.

PMID- 8864097
TI  - Laparoscopic management of acute small-bowel obstruction.
AB  - BACKGROUND: A retrospective review is given of the authors' experience with a
      consecutive series of acute small-bowel obstruction unresponsive to medical
      management. METHODS: There were 33 exploratory laparoscopies. The etiology was
      accurately diagnosed in 100% of the cases. Twenty-five (76%) were secondary to
      postoperative adhesions, of which 18 (72%) were successfully treated by
      laparoscopic lysis of adhesions. Minilaparotomy was needed to treat iatrogenic
      perforation (two), gangrenous bowel (one), and Meckel's diverticulectomy (one).
      Formal laparotomy was utilized for small-bowel resection (two), malignant
      adhesions (two), and intolerance of pneumoperitoneum (one). Four cases of
      incarcerated hernias were treated by conventional herniorrhaphy. RESULTS:
      Overall, 67% of our cases were spared formal laparotomy. CONCLUSION: We conclude
      that laparoscopy is an excellent diagnostic modality in acute small-bowel
      obstruction, the majority of which can be simultaneously managed
      laparoscopically. Laparotomy should be reserved for malignant adhesions, surgical
      misadventure, or when the pathology dictates.

PMID- 8864098
TI  - Endoscopic treatment of a choledochocele in a 2-year-old child.
AB  - Choledochocele is an extremely rare congenital lesion of the biliary tree causing
      abdominal pain, pancreatitis, and obstructive cholestasis. Traditionally the
      therapy for this malformation has been surgery. Recently endoscopic therapy has
      been utilized alternatively for the treatment of choledochocele in adults. We
      report the case of a 2-year-old girl with a choledochocele who was treated by
      endoscopic sphincterotomy and placement of a biliary stent. The prosthesis was
      removed after 4 months. After a follow-up of 20 months the patient remains free
      of symptoms. Our experience suggests that endoscopic treatment of congenital
      biliary disease can be performed accurately. Further studies will be necessary to
      confirm the value of stent implantation in congenital bile duct stenosis.

PMID- 8864099
TI  - Laparoscopic reconstruction of vagina using sigmoid autograft.
AB  - With the advent of advanced laparoscopic techniques in surgery, new applications
      have been found, which have expanded the role of laparoscopy in the gynecological
      field. The aim of this paper is to introduce our laparoscopic technique of taking
      a sigmoid colon autograft for colpopoiesis in a patient with congenital agenesis
      of the vagina. This technique is less invasive and is easy to perform, and it may
      be the best choice of operation in respect to the naturalness and the permanency
      of the vagina that results. The success of this laparoscopic technique of taking
      a sigmoid autograft for colpopoiesis suggests diverse possible applications in
      the future.

PMID- 8864100
TI  - Serum electrolyte abnormalities secondary to Fleet's Phospho-Soda colonoscopy
      prep. A review of three cases.
AB  - The authors report three cases of adverse reactions to commonly used lavage
      solutions generally believed harmless.

PMID- 8864101
TI  - Synergistic benefits of combined technologies in complex, minimally invasive
      surgical procedures. Clinical experience and educational processes.
AB  - The new burden surgical technology must assume demands not only improved
      efficiency and reduced risk, but also diminished cost and resource utilization.
      To this end, we have instituted the use of multiple, sequential technologies in
      complex, minimally invasive procedures: laparoscopic gastric surgery (44 cases),
      spine procedures (38 cases), and colectomies (96 cases). The technologies include
      head-mounted display, 3-D optics, robotic arm, harmonic scalpel, and optical
      access trocars. The combined use of these technologies shortened operative times,
      diminished use of personnel, and as associated with no technical mishap. Surgeon
      concentration and control of the operative environment were increased. In an
      effort to promote combined use of technologies, a structured teaching process was
      designed and implemented. It required five (average) experiences for efficient,
      hands-on implementation of combined technologies. We conclude that combined use
      of sophisticated technologies is safe and efficient; is accomplished by
      structured, moderately intense educational experience; and diminishes cost and
      use of human resources.

PMID- 8864102
TI  - Simultaneous vs staged bilateral video-assisted thoracoscopic surgery.
AB  - It is generally thought that simultaneous bilateral chest surgery carries a high
      morbidity. We reviewed the results of simultaneous (under one anesthesia) vs
      staged bilateral video-assisted thoracoscopic surgery (VATS) from a single
      institution over a 35-month period. From September 1992 to July 1995, we
      performed simultaneous bilateral VATS on 37 patients (31 males, six females, age
      ranging from 15 to 55 years) with spontaneous pneumothorax (20) for bleb
      resections and pleurodesis; thoracodorsal sympathectomy (12) for palmar
      hyperhidrosis and vasospastic disease; and metastatic sarcomas (five) for wedge
      lung resections. During the same period, nine patients with metachronous
      bilateral spontaneous pneumothorax had staged procedures, as did two with digital
      ischemic ulcers for sympathectomy and three with metastatic pulmonary
      osteosarcomas for resection. Mean postoperative hospital stays in days for the
      simultaneous groups were 3.3 for spontaneous pneumothorax, 2.1 for sympathectomy,
      and 1.5 for wedge resection, compared to 2.9, 2.5, and 2.2 for the staged groups,
      respectively (p > 0.05 by Mann-Whitney U tests). Likewise, pain assessment by
      visual analogue scale as well as analgesic requirement showed no significant
      difference between the simultaneous and the staged groups. We conclude that
      simultaneous VATS is not associated with increased morbidity or prolonged
      hospital stay compared to the staged counterparts and provides an attractive
      alternative to the median sternotomy, bilateral posterolateral thoracotomy, or
      transternal (clam-shell) thoracotomy for selected cases of simultaneous bilateral
      lung surgery.

PMID- 8864103
TI  - A new sealing device (Sandwich-disc) for rapid recreation of pneumoperitoneum
      during laparoscopic assisted surgery.
AB  - We have developed a new device which enables rapid sealing of a minilaparotomy
      during laparoscopic assisted surgery to recreate an airtight condition. This
      device consists of a center rod and two discs (7 cm in diameter) which form an
      airtight condition by compressing the inner and outer surfaces of the abdominal
      wall. Advanced laparoscopic procedures requiring both pneumoperitoneum and
      minilaparotomy are facilitated with the use of this device. This new device is
      called the Sandwich-disc: Takasago Medical Industry Co., Ltd.

PMID- 8864104
TI  - CD-ROM multimedia. The step before virtual reality.
AB  - Applications developed using key multimedia elements are finding their way into a
      number of training and information exchange environments including the
      laparoscopy training market. Emerging multimedia-based applications range from
      procedural information for patients to interactive CD-ROM-based applications used
      to train highly skilled surgeons. These products are designed with a high level
      of interactivity that allows the surgeon to plan a surgical procedure, review
      detailed patient information and then merge that information into the surgical
      planning process. Using this new technology, a surgeon now has the ability to
      review CD-ROM-based course materials and efficiently meet continuing education
      requirements. The factor found most limiting in the development of multimedia
      based applications for laparoscopy training is generally not the technology, but
      the limits placed on the technology because of one's reluctance to think beyond
      what is accepted as the norm. Properly implemented, multimedia applications
      developed for laparoscopy training reduce the cost and time associated with
      learning new materials, assist a user in retaining more of the information
      reviewed, and in many cases make the learning experience much more enjoyable.

PMID- 8864111
TI  - The crystal structure of a five-stranded coiled coil in COMP: a prototype ion
      channel?
AB  - Oligomerization by the formation of alpha-helical bundles is common in many
      proteins. The crystal structure of a parallel pentameric coiled coil,
      constituting the oligomerization domain in the cartilage oligomeric matrix
      protein (COMP), was determined at 2.05 angstroms resolution. The same structure
      probably occurs in two other extracellular matrix proteins, thrombospondins 3 and
      4. Complementary hydrophobic interactions and conserved disulfide bridges between
      the alpha helices result in a thermostable structure with unusual properties. The
      long hydrophobic axial pore is filled with water molecules but can also
      accommodate small apolar groups. An "ion trap" is formed inside the pore by a
      ring of conserved glutamines, which binds chloride and probably other monatomic
      anions. The oligomerization domain of COMP has marked similarities with proposed
      models of the pentameric transmembrane ion channels in phospholamban and the
      acetylcholine receptor.

PMID- 8864112
TI  - Nested retrotransposons in the intergenic regions of the maize genome.
AB  - The relative organization of genes and repetitive DNAs in complex eukaryotic
      genomes is not well understood. Diagnostic sequencing indicated that a 280
      kilobase region containing the maize Adh1-F and u22 genes is composed primarily
      of retrotransposons inserted within each other. Ten retroelement families were
      discovered, with reiteration frequencies ranging from 10 to 30,000 copies per
      haploid genome. These retrotransposons accounted for more than 60 percent of the
      Adh1-F region and at least 50 percent of the nuclear DNA of maize. These elements
      were largely intact and are dispersed throughout the gene-containing regions of
      the maize genome.

PMID- 8864113
TI  - Requirement of rigid-body motion of transmembrane helices for light activation of
      rhodopsin.
AB  - Conformational changes are thought to underlie the activation of heterotrimeric
      GTP-binding protein (G protein)-coupled receptors. Such changes in rhodopsin were
      explored by construction of double cysteine mutants, each containing one cysteine
      at the cytoplasmic end of helix C and one cysteine at various positions in the
      cytoplasmic end of helix F. Magnetic dipolar interactions between spin labels
      attached to these residues revealed their proximity, and changes in their
      interaction upon rhodopsin light activation suggested a rigid body movement of
      helices relative to one another. Disulfide cross-linking of the helices prevented
      activation of transducin, which suggests the importance of this movement for
      activation of rhodopsin.

PMID- 8864114
TI  - Control of spatiotemporal coherence of a thalamic oscillation by corticothalamic
      feedback.
AB  - The mammalian thalamus is the gateway to the cortex for most sensory modalities.
      Nearly all thalamic nuclei also receive massive feedback projections from the
      cortical region to which they project. In this study, the spatiotemporal
      properties of synchronized thalamic spindle oscillations (7 to 14 hertz) were
      investigated in barbiturate-anesthetized cats, before and after removal of the
      cortex. After complete ipsilateral decortication, the long-range synchronization
      of thalamic spindles in the intact cortex hemisphere changed into disorganized
      patterns with low spatiotemporal coherence. Local thalamic synchrony was still
      present, as demonstrated by dual intracellular recordings from nearby neurons. In
      the cortex, synchrony was insensitive to the disruption of horizontal
      intracortical connections. These results indicate that the global coherence of
      thalamic oscillations is determined by corticothalamic projections.

PMID- 8864115
TI  - PIN: an associated protein inhibitor of neuronal nitric oxide synthase.
AB  - The neurotransmitter functions of nitric oxide are dependent on dynamic
      regulation of its biosynthetic enzyme, neuronal nitric oxide synthase (nNOS). By
      means of a yeast two-hybrid screen, a 10-kilodalton protein was identified that
      physically interacts with and inhibits the activity of nNOS. This inhibitor,
      designated PIN, appears to be one of the most conserved proteins in nature,
      showing 92 percent amino acid identity with the nematode and rat homologs.
      Binding of PIN destabilizes the nNOS dimer, a conformation necessary for
      activity. These results suggest that PIN may regulate numerous biological
      processes through its effects on nitric oxide synthase activity.

PMID- 8864116
TI  - Change of a catalytic reaction carried out by a DNA replication protein.
AB  - The RepA protein of plasmid pC194 initiates and terminates rolling circle
      replication. At initiation, it forms a 5'-phosphotyrosyl DNA link, whereas at
      termination, a glutamate residue directs hydrolytic cleavage of the newly
      synthesized origin, and the resulting 3'-hydroxyl group undergoes
      transesterification with the phosphotyrosine link. The protein is thus released
      from DNA, and the termination is uncoupled from reinitiation of replication.
      Replacement of the glutamate with tyrosine in RepA altered this mechanism, so
      that termination occurred by two successive transesterifications and became
      coupled to reinitiation. This result suggests that various enzymes involved in
      DNA cleavage and rejoining may have similar mechanistic and evolutionary roots.

PMID- 8864117
TI  - A role for phosphoinositide 3-kinase in bacterial invasion.
AB  - Listeria monocytogenes is a bacterial pathogen that invades cultured
      nonphagocytic cells. Inhibitors and a dominant negative mutation were used to
      demonstrate that efficient entry requires the phosphoinositide (PI) 3-kinase
      p85alpha-p110. Infection with L. monocytogenes caused rapid increases in cellular
      amounts of PI(3, 4)P2 and PI(3,4,5)P3, indicating that invading bacteria
      stimulated PI 3-kinase activity. This stimulation required the bacterial protein
      InlB, host cell tyrosine phosphorylation, and association of p85alpha with one or
      more tyrosine-phosphorylated proteins. This role for PI 3-kinase in bacterial
      entry may have parallels in some endocytic events.

PMID- 8864118
TI  - An essential role for NF-kappaB in preventing TNF-alpha-induced cell death.
AB  - Studies on mice deficient in nuclear factor kappa B (NF-kappaB) subunits have
      shown that this transcription factor is important for lymphocyte responses to
      antigens and cytokine-inducible gene expression. In particular, the RelA (p65)
      subunit is required for induction of tumor necrosis factor-alpha (TNF-alpha)
      dependent genes. Treatment of RelA-deficient (RelA-/-) mouse fibroblasts and
      macrophages with TNF-alpha resulted in a significant reduction in viability,
      whereas RelA+/+ cells were unaffected. Cytotoxicity to both cell types was
      mediated by TNF receptor 1. Reintroduction of RelA into RelA-/- fibroblasts
      resulted in enhanced survival, demonstrating that the presence of RelA is
      required for protection from TNF-alpha. These results have implications for the
      treatment of inflammatory and proliferative diseases.

PMID- 8864119
TI  - TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF
      kappaB.
AB  - Many cells are resistant to stimuli that can induce apoptosis, but the mechanisms
      involved are not fully understood. The activation of the transcription factor
      nuclear factor-kappa B (NF-kappaB) by tumor necrosis factor (TNF), ionizing
      radiation, or daunorubicin (a cancer chemotherapeutic compound), was found to
      protect from cell killing. Inhibition of NF-kappaB nuclear translocation enhanced
      apoptotic killing by these reagents but not by apoptotic stimuli that do not
      activate NF-kappaB. These results provide a mechanism of cellular resistance to
      killing by some apoptotic reagents, offer insight into a new role for NF-kappaB,
      and have potential for improvement of the efficacy of cancer therapies.

PMID- 8864120
TI  - Suppression of TNF-alpha-induced apoptosis by NF-kappaB.
AB  - Tumor necrosis factor alpha (TNF-alpha) signaling gives rise to a number of
      events, including activation of transcription factor NF-kappaB and programmed
      cell death (apoptosis). Previous studies of TNF-alpha signaling have suggested
      that these two events occur independently. The sensitivity and kinetics of TNF
      alpha-induced apoptosis are shown to be enhanced in a number of cell types
      expressing a dominant-negative IkappaBalpha (IkappaBalphaM). These findings
      suggest that a negative feedback mechanism results from TNF-alpha signaling in
      which NF-kappaB activation suppresses the signals for cell death.

PMID- 8864121
TI  - Conditional circadian dysfunction of the Arabidopsis early-flowering 3 mutant.
AB  - Photoperiodic responses, such as the daylength-dependent control of reproductive
      development, are associated with a circadian biological clock. The photoperiod
      insensitive early-flowering 3 (elf3) mutant of Arabidopsis thaliana lacks
      rhythmicity in two distinct circadian-regulated processes. This defect was
      apparent only when plants were assayed under constant light conditions. elf3
      mutants retain rhythmicity in constant dark and anticipate light/dark transitions
      under most light/dark regimes. The conditional arrhythmic phenotype suggests that
      the circadian pacemaker is intact in darkness in elf3 mutant plants, but the
      transduction of light signals to the circadian clock is impaired.

PMID- 8864122
TI  - Protection from natural killer cell-mediated lysis by HLA-G expression on target
      cells.
AB  - The outermost layer of the human placenta is devoid of classical class I human
      leukocyte antigens (HLA-A, HLA-B, and HLA-C) and class II proteins (HLA-DR, HLA
      DQ, and HLA-DP). Although this prevents recognition by maternal T lymphocytes,
      the lack of class I molecules leaves these cells susceptible to attack by natural
      killer (NK) cells. However, trophoblast cells directly in contact with the
      maternal tissues express the class I molecule HLA-G, which may be involved in
      protecting the trophoblast from recognition by NK cells. Here evidence is
      provided that expression of HLA-G is sufficient to protect otherwise susceptible
      target cells from lysis by activated NK1 and NK2 cell lines and clones that are
      specific for distinct groups of HLA-C alleles. The receptors on NK cells that
      recognize HLA-G are also identified.

PMID- 8864123
TI  - Decreased resistance to bacterial infection and granulocyte defects in IAP
      deficient mice.
AB  - Granulocyte [polymorphonuclear leucocyte (PMN)] migration to sites of infection
      and subsequent activation is essential for host defense. Gene-targeted mice
      deficient for integrin-associated protein (IAP, also termed CD47) succumbed to
      Escherichia coli peritonitis at inoccula survived by heterozygous littermates. In
      vivo, they had an early defect in PMN accumulation at the site of infection. In
      vitro, IAP-/- PMNs were deficient in beta3 integrin-dependent ligand binding,
      activation of an oxidative burst, and Fc receptor-mediated phagocytosis. Thus,
      IAP plays a key role in host defense by participating both in PMN migration in
      response to bacterial infection and in PMN activation at extravascular sites.

PMID- 8864124
TI  - Hyperresponsive B cells in CD22-deficient mice.
AB  - CD22 is a surface glycoprotein of B lymphocytes that is rapidly phosphorylated on
      cytoplasmic tyrosines after antigen receptor cross-linking. Splenic B cells from
      mice with a disrupted CD22 gene were found to be hyperresponsive to receptor
      signaling: Heightened calcium fluxes and cell proliferation were obtained at
      lower ligand concentrations. The mice gave an augmented immune response, had an
      expanded peritoneal B-1 cell population, and contained increased serum titers of
      autoantibody. Thus, CD22 is a negative regulator of antigen receptor signaling
      whose onset of expression at the mature B cell stage may serve to raise the
      antigen concentration threshold required for B cell triggering.

PMID- 8864125
TI  - Visual pigment gene structure and the severity of color vision defects.
AB  - Rearrangements of the visual pigment genes are associated with defective color
      vision and with differences between types of red-green color blindness. Among
      individuals within the most common category of defective color vision,
      deuteranomaly, there is a large variation in the severity of color vision loss.
      An examination of specific photopigment gene sites responsible for tuning
      photopigment absorption spectra revealed differences that predict these
      variations in the color defect. The results indicate that the severity of the
      defect in deuteranomalous color vision depends on the degree of similarity among
      the residual photopigments that serve vision in the color-anomalous eye.

PMID- 8864126
TI  - Protein tyrosine phosphorylation in leukocyte activation through receptors for
      IgG.
AB  - Membrane receptors for the Fc portion of immunoglobulin G (IgG) antibodies
      (Fc(gamma)Rs) are expressed on almost every type of hematopoietic cells, where
      they mediate a wide variety of effector functions. A high degree of structural
      heterogeneity exists among Fc(gamma)Rs. The biological significance of such
      heterogeneity is unknown, since the structural diversity does not appear to be
      reflected in the binding specificity nor in the effector functions that each
      distinct receptor is able to mediate. Recent work has emphasized the essential
      role of protein tyrosine phosphorylation in the initiation of transmembrane
      signaling by these receptors. In this article we review the role of protein
      tyrosine phosphorylation in signal transduction by the different types of
      Fc(gamma)Rs in order to assess to what extent the structural heterogeneity of
      this receptor family is related to different activation pathways utilized by each
      of its members.

PMID- 8864127
TI  - Signaling by IL-2 and related cytokines: JAKs, STATs, and relationship to
      immunodeficiency.
AB  - Cytokines that bind to the interleukin-2 (IL-2) receptor common gamma chain
      (gamma c), including IL-2, IL-4, IL-7, IL-9, and IL-15, are important for the
      growth and differentiation of T and B lymphocytes, natural killer cells,
      macrophages, and monocytes. These cytokines have overlapping biological effects
      that in part result from the use of the shared receptor subunit gamma c. Recently
      it has become clear that these cytokines activate a number of important
      intracellular signaling molecules, including the Janus kinases JAK1 and JAK3 and
      members of the transcription factor family of signal transducers and activators
      of transcription (STATs). The discovery of these signaling pathways has led to
      important new insights into their role in lymphocyte maturation, as it has
      emerged that mutations in the genes encoding both gamma c and JAK3 result in
      similar forms of severe combined immunodeficiency (SCID). In this review we
      examine the structure and function of cytokine receptors and the signaling
      pathways involved in their regulation of gene expression. Furthermore, we discuss
      recent advances that have led to a better understanding of how cytokines elicit
      intracellular responses, as well as their role in normal lymphoid development.

PMID- 8864128
TI  - Hepatic catabolism of intravenously administered pro-macrophage-stimulating
      protein in mice.
AB  - We injected 125I-pro-macrophage-stimulating protein (pro-MSP) intravenously into
      normal mice to determine its clearance from the circulation and to test for
      conversion of pro-MSP to the biologically active heterodimer in the absence of
      inflammation or tissue injury. Pro-MSP was cleared from the circulation with a
      half-life of approximately 100 min. This rapid clearance was not peculiar to 125I
      pro-MSP, since clearance rates of unlabeled pro-MSP and of 125I-bovine serum
      albumin were comparable. The liver was the major locus of radioactivity 10-20 min
      after the intravenous injection of 125I-pro-MSP. By 90 min, over 60% of total
      recovered radioactivity was in the small intestine. Reflecting gastrointestinal
      transit, counts decreased in the small intestine and appeared in the colon by 180
      min. Essentially all counts in urine and feces obtained at later times were
      soluble in trichloracetic acid. These findings reflected rapid hepatic
      proteolysis of pro-MSP to fragments undetectable by antibody to pro-MSP; within
      20 min after intravenous administration, immunoprecipitable counts were only 22%
      of the total liver extract radioactivity. Comparison of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and radioautography data for
      immunoprecipitated plasma and liver extract revealed no evidence for hepatic
      conversion of pro-MSP to MSP. Thus, the hepatic catabolic pathway of pro-MSP is
      degradative and does not yield mature MSP. The results support our view that MSP
      is not released into the circulation but is generated at specific extravascular
      loci by pro-MSP convertases.

PMID- 8864129
TI  - Elevated TNF-alpha and inducible nitric oxide production by alveolar macrophages
      after exposure to a nitrite inhalant.
AB  - Abuse of nitrite inhalants, widespread among male homosexuals, has been
      identified by epidemiological studies as an independent risk factor for AIDS and
      for Kaposi's sarcoma. Subchronic exposure of mice to inhaled isobutyl nitrite was
      previously found to impair the tumoricidal activity of peritoneal macrophages.
      Because inhalants would be expected to have the greatest effects on cells in the
      lung, alveolar macrophages from exposed mice were examined in this study. Mice
      were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 min/day
      for 14 days. Following this treatment, the lungs of exposed mice had large
      increases in cellularity, both in the alveolar septa and within the alveoli.
      Bronchoalveolar lavages also contained increased numbers of cells. Alveolar
      macrophages collected from treated mice had increased tumoricidal activity
      compared with controls and produced higher levels of inducible nitric oxide and
      tumor necrosis factor-alpha (TNF-alpha). The frequency of alveolar cells
      secreting TNF-alpha was increased ninefold in mice exposed to the inhalant. Cell
      influx into the lung, as indicated by the presence of red blood cells in lung
      lavages, was evident after only a single 45-min exposure to inhaled isobutyl
      nitrite at doses as low as 300 ppm.

PMID- 8864130
TI  - Interaction of murine dendritic cells with collagen up-regulates allostimulatory
      capacity, surface expression of heat stable antigen, and release of cytokines.
AB  - In vivo, dendritic cells (DC) reside in direct proximity to extracellular matrix
      (ECM) proteins. Because ECM proteins affect morphology and function of a number
      of cell types, this study investigated potential effects of ECM proteins on
      functional properties of DC. DC were generated from murine bone marrow cultures,
      supplemented with granulocyte-macrophage colony-stimulating factor, and
      subsequently cultured on tissue culture plates coated with various ECM proteins.
      Among the ECM proteins tested, collagen (COL) up-regulated the T cell stimulatory
      capacity of DC. This effect was accompanied by sustained surface expression of
      the co-stimulatory molecule heat stable antigen on DC and by enhanced release of
      interleukin-1 and interleukin-6, respectively. Because fibronectin or solubilized
      COL were unable to cause similar changes in DC phenotype or function, we conclude
      that adherence to COL interferes specifically with DC function. These data
      suggest that ECM proteins may be involved in regulation of DC phenotype as well
      as in their functional activation.

PMID- 8864131
TI  - Mechanisms regulating macrophage-induced nitric oxide production by spontaneously
      transformed hamster fibroblasts.
AB  - Nitric oxide has been implicated as an important effector molecule involved in
      tumor cell growth and cytotoxicity. In these studies we examined mechanisms
      regulating nitric oxide production by hamster tumor cells. Cocultures of hamster
      alveolar macrophages (HAM) and spontaneously transformed hamster embryonic
      fibroblasts (STHE cells) produced significant quantities of nitric oxide in
      response to lipopolysaccharide (LPS). Culture supernatants from HAM treated with
      LPS also stimulated nitric oxide production by STHE cells, whereas tumor cell
      culture supernatants had no effect on HAM. These data, together with the findings
      that paraformaldehyde treatment of STHE cells, but not macrophages, completely
      abrogated nitric oxide production in the cocultures demonstrate that the tumor
      cells were the source of this mediator. In contrast to STHE cells, STHE-83/20
      cells, a highly malignant variant, did not produce nitric oxide in response to
      HAM or HAM culture supernatants even in the presence of LPS. Both anti-tumor
      necrosis factor-alpha (TNF-alpha) and anti-interleukin-1alpha (IL-1alpha)
      antibodies inhibited HAM-induced nitric oxide production by STHE cells. However,
      the kinetics of their effects were different. Moreover, although the nitric oxide
      stimulating activity in HAM culture supernatants was abrogated by anti-TNF-alpha
      antibody, it was only minimally reduced by anti-IL-1alpha antibody. These data
      demonstrate that TNF-alpha and IL-1alpha play distinct roles in induction of
      nitric oxide synthesis in STHE cells. HAM were also found to suppress
      proliferation of STHE cells, an effect that was inhibited by anti-TNF-alpha
      antibody, but not NG-monomethyl-L-arginine, which blocks nitric oxide synthase.
      Abrogation of macrophage-induced cytostasis in STHE cells by anti-TNF-alpha
      antibody was associated with decreased nitric oxide production. Thus TNF-alpha
      released by macrophages may indirectly activate STHE cells for nitric oxide
      synthesis by suppressing tumor cell proliferation.

PMID- 8864132
TI  - The inhibitory effect of prostaglandin E2 on rat neutrophil aggregation.
AB  - Rat peritoneal neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine
      (fMLP) produce an aggregation response that can be inhibited by prostaglandin E2
      (PGE2) with an IC50 value of 2.6 x 10(-9) M. Although PGE2 can stimulate [3H]cAMP
      production in neutrophils (EC50 4.3 x 10(-8) M), the anti-aggregation response
      cannot be significantly attenuated by inhibitors of adenylate cyclase or protein
      kinase A, neither can it be potentiated by inhibition of phosphodiesterase
      activity. Despite these observations, it still remains possible that PGE2
      mediated inhibition of rat neutrophil aggregation is a cAMP-dependent response
      mediated by highly localized changes in neutrophil cAMP. The inhibitory effect of
      PGE2 does not appear to depend on effects on intracellular calcium or K(ATP)
      channels. Similarities exist between PGE2 and the profile of activity of
      phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors, suggesting that PI 3
      kinase is a possible target for PGE2 action in rat neutrophils.

PMID- 8864133
TI  - Gadolinium chloride inhibits Kupffer cell nitric oxide synthase (iNOS) induction.
AB  - Kupffer cells (KC) are the phagocytic macrophages of the liver. The rare earth
      metal, gadolinium (GdCl3), is a lanthanide, which, after phagocytosis by the KC,
      has been found to alter various aspects of KC physiology. In this study, we
      describe for the first time that the in vivo administration of GdCl3 to rats
      decreases the release of NO by isolated rat KC in response to lipopolysaccharide.
      Western blot analysis shows decreased expression of both inducible nitric oxide
      synthase as well as total cellular calmodulin after GdCl3 treatment. Possible
      mechanisms for this phenomenon are suggested.

PMID- 8864134
TI  - Eosinophil viability during immunoglobulin-induced degranulation.
AB  - Eosinophil adhesion and degranulation appear to be associated with cell death.
      Eosinophils bound avidly and degranulated with secretory immunoglobulin A (sIgA)-
      and IgG-coupled Sepharose 4B beads but bound poorly and did not degranulate with
      ovalbumin beads. Through the use of dye staining, we found that about 50% of the
      bound eosinophils were dead by 4 h, regardless of the protein coating. Colchicine
      and reduced calcium concentration inhibited binding to beads and eosinophil
      degranulation in a concentration-dependent manner but did not decrease the
      percentages of dead bound eosinophils. Electron microscopy showed that
      eosinophils bound to and spread over bead surfaces. Typical granule exocytosis
      with release of membrane-free granules occurred in about 20% of bound
      eosinophils. Eosinophil degeneration and lysis with release of membrane-coated
      granules occurred in about 50% of bound eosinophils; often only membrane-bound
      granules were present. Therefore, bound eosinophils degranulate both by classical
      exocytosis and by release after cytolytic degeneration. By increasing the numbers
      of bound cells, both IgG and sIgA increase the numbers of dying cells.

PMID- 8864135
TI  - Regulation of microglial activation by TGF-beta, IL-10, and CSF-1.
AB  - Microglia are the resident macrophages of the brain and as such are active
      participants in immune responses in the central nervous system. Normal resting
      microglia express low levels of MHC class I and class II antigens and do not
      produce proinflammatory cytokines. However, microglial immune functions are
      induced in areas of infection or injury. To understand regulation of cytokines
      that are secreted by and act upon microglia, we examined production of
      interleukin (IL) -12, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide
      (NO) by lipopolysaccharide (LPS)-stimulated microglia. We observed secretion of
      IL-12, TNF-alpha, and NO following stimulation of microglia with LPS. Addition of
      IL-10 suppressed TNF-alpha, IL-12, and NO production. Transforming growth factor
      beta (TGF-beta) also inhibited TNF-alpha and NO but did not affect IL-12
      secretion. IL-12 secretion became sensitive to TGF-beta inhibition when microglia
      were cultured in the absence of CSF-1. In addition to its effect on the response
      to TGF-beta, CSF-1 suppressed the response of microglia to LPS. These data
      suggest that CSF-1 may contribute to the immunologically privileged status of the
      central nervous system.

PMID- 8864136
TI  - M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated
      giant cells with distinct phenotypes.
AB  - Multinucleated giant cells (MGC) are a hallmark of granulomatous reactions but
      the mechanisms that regulate their formation are unknown. To address this issue,
      we cultured resident alveolar macrophages (AM) from rat lung and examined the
      effects of defined cytokines on AM differentiation and MGC formation. The
      presence of MGC was found after 3 days in culture with maximal numbers obtained
      at 7 days and thereafter (up to 21 days). Macrophage colony-stimulating factor (M
      CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (25-75 U/mL)
      stimulated the formation of MGC (up to 4-fold), whereas interleukin (IL) -3, IL
      10, and interferon-gamma (IFN-gamma) had no stimulatory effect. Interestingly,
      MGC with distinct phenotypes were observed in AM cultures: (1) spherical MGC with
      3-16 nuclei, dense cytoplasm, and lower expression of beta3 integrin (Type 1) and
      (2) irregular MGC with 3-30 nuclei, thin and vacuolated cytoplasm, and higher
      expression of beta3 integrin (Type 2). Furthermore, the actions of M-CSF and GM
      CSF on AM were found to be different. GM-CSF promoted, in AM cultures, the
      appearance of an elongated fibroblastoid phenotype and stimulated mostly the
      formation of Type 2 MGC. In contrast, M-CSF did not cause significant change in
      the general morphology of regular AM but stimulated the appearance of both Type 1
      and Type 2 MGC. Reverse transcriptase-polymerase chain reaction analysis
      demonstrated that, under these conditions, M-CSF induced GM-CSF gene expression
      in AM. In addition, neutralizing antibodies against M-CSF selectively decreased
      the formation of Type 1 MGC, whereas neutralizing anti-GM-CSF inhibited Type 2
      formation. These data suggest that M-CSF promotes AM differentiation into Type 1
      MGC, whereas GM-CSF stimulates the formation of Type 2 and that M-CSF and GM-CSF
      may selectively regulate in an autocrine fashion AM differentiation into distinct
      MGC.

PMID- 8864137
TI  - Interferon-gamma reduces Ia+ dendritic cell traffic to the lung.
AB  - MHC class II+ lung dendritic cells (DC) increase in number following treatment of
      animals with interferon-gamma (IFN-gamma) [Kradin et al. (1991) Am. J. Resp. Mol.
      Biol. 4, 210; Gong et al. (1992)J. Exp. Med. 175, 797]. To test whether this is
      due to increased sequestration and/or trafficking of DC to the lung, bone marrow
      DC from BALB/c mice were obtained by culturing bone marrow with granulocyte
      macrophage colony-stimulating factor (GM-CSF). Recipient BALB/c mice were
      injected intraperitoneally (i.p.) for 4 days with one of the following: IFN
      gamma, dexamethasone (Dex), or phosphate-buffered saline (PBS). Twenty-four hours
      after the last dose, they were injected intravenously (i.v.) with
      carboxyfluorescein (F1) -labeled DC (1 x 10(6)/mouse) and killed 4 h later. DC,
      double immunostained for Ia and F1, were quantified by morphometry in frozen
      sections of lung. The number of injected dual-labeled DC/cm2 was reduced by 90%
      in IFN-gamma-treated mice. By contrast, there was no significant difference
      between Dex- and PBS-treated animals in the number of double-labeled DC retained
      in pulmonary capillaries. Biodistribution and imaging studies were conducted on
      IFN-gamma- and PBS-treated mice using 111In-labeled DC. Reduced radioactivity in
      the lung was accounted for by an equivalent increase in the liver of IFN-gamma
      treated mice; imaging studies confirmed these observations. Removal of >80% of
      alveolar macrophages (AM) by pretreatment with intratracheally administered
      chlodronate-loaded liposomes did not change the biodistribution of DC in IFN
      gamma- and PBS-injected mice. Serum levels of tumor necrosis factor-alpha (TNF
      alpha and nitrite/nitrate in IFN-gamma-treated mice were similar to those of
      controls. Immunostaining for inducible nitric oxide synthase (iNOS), however,
      revealed a 1.5-and 6-fold increase in the number of positively stained cells in
      the lung and liver, respectively, of IFN-gamma-treated mice; the number of iNOS
      expressing cells was markedly reduced in Dex-treated animals relative to
      controls. To test whether the systemic treatment with IFN-gamma stimulated the
      cytotoxic activity of Kupffer cells, mice were injected with chlodronate
      liposomes 5 days before death. After treating the mice in the ensuing 4 days with
      IFN-gamma or PBS, biodistribution and imaging studies with 111In-labeled DC were
      conducted on the 5th day. After administration of chlodronate liposomes, there
      was a significant increase in the radioactivity detected in the lungs of IFN
      gamma-injected mice but not in those of PBS- injected controls, a finding
      confirmed by imaging studies. We conclude that IFN-gamma treatment augmented
      Kupffer cell cytotoxic activity, which, in turn, effectively reduced the number
      of injected DC in circulation, with the result that fewer of these cells were
      retained in the lung vasculature. We further conclude that IFN-gamma increases
      the number of Ia+ lung DC by up-regulating Ia expression of resident Ia- DC
      precursors and not by promoting the migration of circulating DC to the lung.

PMID- 8864138
TI  - Role of interferon-gamma in immunity to herpes simplex virus.
AB  - Removal of herpes simplex virus (HSV)-infected cells from peripheral sites such
      as the skin is mainly an activity of T cells, particularly the CD4+ T subset.
      Such cells orchestrate an inflammatory response with interferon-gamma (IFN-gamma)
      appearing to play the essential role in viral clearance. In accordance with this
      hypothesis, we show that infection of BALB/c background mice expressing the
      knockout phenotype for IFN-gamma (GKO mice) are significantly more susceptible to
      the development of cutaneous zosteriform lesions than are wild-type. However,
      following HSV immunization, GKO mice become solidly immune to the development of
      zosteriform lesions. In addition, the transfer of T cells from immune GKO mice to
      nude mice recipients renders them resistant to zosteriform lesions. Our results
      are discussed in terms of the major and compensatory mechanisms available to the
      body to effect immunity to viral infections.

PMID- 8864139
TI  - T cell activation via the disialoganglioside GD3: analysis of signal
      transduction.
AB  - The monoclonal antibody (mAb) R24 is a murine immunoglobulin G3 (IgG3) that
      reacts with the GD3 disialoganglioside present on melanoma cells as well as a
      subset of T cells. R24 mAb has induced antitumor responses both alone and in
      combination with interleukin-2 (IL-2) in clinical trials. We have reported T cell
      activation via GD3 as measured by the induction of tyrosine phosphorylation. In
      this study a more detailed analysis of signal transduction after ligation of GD3
      was performed in an attempt to understand the mechanism of in vivo therapeutic
      benefits observed. Analysis of subsequent events indicated that GD3 engagement
      resulted in phospholipase C(gamma) phosphorylation and calcium flux. When ras
      associated events were examined, GD3 signaling resulted in ras activation as
      determined by GDP/GTP conversion as well as dose-and time-dependent IP3
      activation. In addition, the majority of the IP3 activation by GD3 was inhibited
      by herbimycin A pretreatment. Elucidation of the nature and potential role of
      this moiety in GD3 signal transduction should be useful. Collectively, these data
      suggest a novel mechanism of T cell activation via a single, non-protein, surface
      moiety. This novel form of T cell-mediated activation may permit the delivery and
      local activation of effector cells at the tumor resulting in site-specific
      activation of the immune system.

PMID- 8864140
TI  - Differential screening identifies genetic markers of monocyte to macrophage
      maturation.
AB  - Maturation of cells of the mononuclear phagocyte lineage from bone marrow
      precursors to tissue macrophages (MAC) via circulating blood monocytes (MO) is a
      multistep process only partially understood. Similarly, MAC differentiation can
      be observed if MO are cultured in vitro. In an attempt to further characterize
      molecular changes occurring during this process we carried out differential
      screening of a MO-derived MAC cDNA library using MO and MAC cDNA. After
      subcloning and confirmation by a second round of screening, partial sequencing of
      41 cDNA clones was performed. In 33 clones the sequences of 7 different
      previously identified cDNAs were found. The mRNA expression of two of the
      corresponding genes (apolipoprotein E, ferritin light chain) is already known to
      be up-regulated during MAC maturation. For one gene (cathepsin B), a specific up
      regulation of mRNA expression could be shown corresponding to previous protein
      data. For four genes [human cartilage glycoprotein (HC-gp39), osteopontin, type
      IV collagenase, and tryptophanyl-tRNA synthetase] the specific expression in MAC
      versus MO was previously unknown but could be confirmed by the use of Northern
      blot analysis. Of these genes, HC-gp39 is especially interesting because it is
      only expressed during the late stages of MAC differentiation.

PMID- 8864141
TI  - Activation of Src-family tyrosine kinases during Fas-induced apoptosis.
AB  - Stimulation of several human and murine hematopoietically derived cell lines with
      anti-Fas antibodies induced increased tyrosine phosphorylation of a panel of
      proteins observed in whole-cell lysates. In the human T cell line Jurkat, the
      activity of a 56-kDa tyrosine kinase was likewise activated by anti-Fas
      antibodies. Immunoprecipitation studies of anti-Fas-stimulated human Jurkat and
      murine 2B4.11 T cells revealed activation of the Src-family tyrosine kinases Lck
      and Fyn. Fas receptor-induced tyrosine phosphorylation of p120 c-cbl proto
      oncogene product was observed in Jurkat T cells. Pharmacological experiments
      demonstrated that pretreatment of Jurkat cells with tyrphostins inhibited Fas
      induced apoptosis; likewise, Lck activity was inhibited by tyrphostins in a dose
      dependent fashion. Finally, Lck derived from unstimulated Jurkat T cells formed
      stable complexes with the intracellular domain of the Fas receptor. These data
      are consistent with the notion that expression and activation of members of the
      Src-family kinases is required for Fas-induced cell death in T lymphocytes and
      consistent with recent findings demonstrating decreased Fas-mediated thymocytic
      death in Fyn-knockout mice.

PMID- 8864142
TI  - Breast cancer incidence and mortality--United States, 1992.
AB  - Breast cancer is the most commonly diagnosed nondermatologic cancer and the
      second leading cause of cancer-related deaths among women in the United States.
      In 1996, a total of 184,300 new cases of and 44,300 deaths from invasive breast
      cancer are projected among women. To assess trends in incidence and death rates
      for breast cancer among U.S. women, CDC analyzed national incidence data from the
      National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)
      program and death-certificate data from CDC's National Center for Health
      Statistics (NCHS). This report presents incidence and death rates for breast
      cancer for 1992 (the most recent year for which SEER data were available) and
      summarizes trends in these rates for 1973-1992. Overall, these findings indicate
      that incidence rates for invasive breast cancer increased among women during 1973
      1987 and stabilized during 1988-1992, while mortality rates remained stable
      during 1973-1988 and decreased during 1989-1992.

PMID- 8864143
TI  - What is comorbidity--fact or artefact?

PMID- 8864144
TI  - Critical issues in the evaluation of comorbidity of psychiatric disorders.
AB  - Comorbidity has become an increasingly popular theme in psychiatry and clinical
      psychology, although its heuristic value was recognised long ago. Frequently used
      in research and practice, no definition of comorbidity is uniformly accepted and
      it has no comprehensive and coherent theoretical framework. These factors have
      led to substantial variation in the magnitude of comorbidity across studies. The
      variability in the definition, assessment and design of comorbidity studies has
      led to an increasingly complex and confusing picture about the potential value of
      this concept. The full exploration of mechanisms of comorbidity requires an
      interdisciplinary approach to investigating nosology, assessment, and underlying
      models of comorbidity, as well as experimental study designs beyond the scope of
      clinical and epidemiological studies. A more precise specification of comorbidity
      patterns might help identify common biochemical and cognitive markers relevant in
      the aetiology of specific mental disorders as well as comorbid conditions.
      Critical issues that might help us understand and explain the variability of
      findings are described.

PMID- 8864145
TI  - Comorbidity of DSM-III-R major depressive disorder in the general population:
      results from the US National Comorbidity Survey.
AB  - General population data are presented on the prevalence and correlates of
      comorbidity between DSM-III-R major depressive disorder (MDD) and other DSM-III-R
      disorders. The data come from the US National Comorbidity Survey, a large general
      population survey of persons aged 15-54 years in the non-institutionalised
      civilian population. Diagnoses are based on a modified version of the Composite
      International Diagnostic Interview (CIDI). The analysis shows that most cases of
      lifetime MDD are secondary. In the sense that they occur in people with a prior
      history of another DSM-III-R disorder. Anxiety disorders are the most common
      primary disorders. The time-lagged effects of most primary disorders on the risk
      of subsequent MDD continue for many years without change in magnitude. Secondary
      MDD is, in general, more persistent and severe than pure or primary MDD. This has
      special public health significance because lifetime prevalence of secondary MDD
      has increased in recent cohorts, while the prevalence of pure and primary
      depression has remained unchanged.

PMID- 8864146
TI  - Comorbidity of mood disorders: a longitudinal prospective study.
AB  - From the Zurich cohort study (n = 591), the association of major depressive
      episodes and recurrent brief depression (RBD) with other psychiatric disorders is
      presented cross-sectionally at age 28 and 30 years, and over ten years (age 20 to
      30 years). Longitudinally, the odds ratios of major depression are highest with
      dysthymia (4.4), generalised anxiety disorder (4.4), panic disorder (2.7),
      hypomania and agoraphobia (2.6), and social phobia (2.4). There is a significant
      association with cannabis consumption and smoking. Follow-up data over nine years
      are available for 41 patients with a major depressive disorder (MDD) and 62 with
      RBD: approximately 20% of MDD patients did not receive a diagnosis during follow
      up. Major depression reoccurred in 32%, became bipolar in 24%, or developed into
      RBD in 24%. RBD remitted in 41%, reoccurred in 35%, turned into major depression
      in 22%, and became bipolar in only 7%. Longitudinally, MDD and RBD show a
      symmetrical diagnostic change in a quarter of the cases. There is no substantial
      development of MDD or RBD into minor depression or generalised anxiety disorder.
      Thirteen per cent of those with RBD later developed panic disorder.

PMID- 8864147
TI  - Depression comorbid with anxiety: results from the WHO study on psychological
      disorders in primary health care.
AB  - The World Health Organization collaborative study on "Psychological Problems in
      General Health Care" investigated the form, frequency, course and outcome of
      common psychological problems in primary care settings at 15 international sites.
      The research employed a two-stage case-finding procedure. GHQ-12 was administered
      to 25916 adults who consulted health-care services. The second-stage assessment
      (n = 5438) consisted of the Composite international Diagnostic Interview (CIDI),
      the Social Disability Schedule, and questionnaires. Possible cases or borderline
      cases of mental disorder, and a sample of known cases, were followed up at three
      months and one year. Using standard diagnostic algorithms (ICD-10), prevalence
      rates were calculated for current disorder (one-month) and lifetime experience
      disorder. Well-defined psychological problems are frequent in all the general
      health-care settings examined (median 24.0%). Among the most common were
      depression anxiety, alcohol misuse, somatoform disorders, and neurasthenia. Nine
      per cent of patients suffered from a "subthreshold condition" that did not meet
      diagnostic criteria but had clinically significant symptoms and functional
      impairment. The most common co-occurrence was depression and anxiety. Comorbidity
      increases the likelihood of recognition of mental disorders in general health
      care, and the likelihood of receiving treatment.

PMID- 8864148
TI  - A dimensional model for common mental disorders.
AB  - Although categorical diagnoses are valued by clinicians and those wishing to
      collect homogeneous groups of patients for research projects, in the field of non
      psychotic mental disorders they correspond poorly to actual clinical syndromes.
      Indeed, patients often satisfy several sets of categorical criteria
      simultaneously. A more parsimonious representation of symptomatology can be
      obtained by using a dimensional model for symptoms-with two correlated axes
      corresponding to anxiety and depression for ratings derived from the Present
      State Examination. The Composite International Diagnostic Interview is likely to
      produce a third dimension-so-matic symptoms-because of a radically different
      symptom content. Preliminary data analysis indicates that the somatic symptoms
      dimension correlates with both anxiety and depression. Symptomatic individuals in
      particular areas of dimensional space will satisfy several criteria for
      categorical diagnoses, and thus display comorbidity. However, evidence that these
      disorders are distinct is far from persuasive, as they appear to share several
      common causes.

PMID- 8864149
TI  - Social factors and comorbidity of depressive and anxiety disorders.
AB  - Differences in rates of depression across and between populations can be
      considerable and are largely determined by psychosocial factors. Such findings
      have important implications for comorbidity. On the basis of multiplying
      independent probabilities, the proportion of comorbid conditions increases as
      base rates of the disorders increase in a population. If such a chance
      combination has clinical implications, it would appear to be a "fact" of
      significance irrespective of biological underpinnings. In a recent survey of 404
      women living with at least one child in an inner-city area, the rate of both
      anxiety and depression was highly related to the childhood experiences of neglect
      and abuse. However, adversity in adult life (e.g. widowhood or divorce), which
      might be expected to relate to current stressors, was only related to the rate of
      depression. The two risk factors had a considerable impact on comorbidity by
      increasing the rate of each disorder and thus the probability of their occurring
      together. They had a lesser impact as "common antecedents". If both influences
      are considered, such adversity explains around half of the comorbidity. This is a
      conservative estimate of the impact of psychosocial factors.

PMID- 8864150
TI  - Comorbidity and boundaries of affective disorders with anxiety disorders and
      substance misuse: results of an international task force.
AB  - Associations between affective disorders, anxiety disorders, and substance use
      disorders were examined in epidemiological studies conducted in Germany,
      Switzerland, Puerto Rico, and the mainland US. There was a remarkable degree of
      similarity across studies in the magnitude and type of specific disorders
      associated with the affective disorders. Comorbidity with affective disorders was
      greater for the anxiety disorders than for substance misuse. Panic disorder was
      the subtype of anxiety that was most highly comorbid with depression. Social
      phobia was the specific phobic type with the strongest association with the
      affective disorders. The magnitude of associations between substance misuse and
      affective disorders generally was quite low and less consistent across sites. No
      major differences were found in the patterns of comorbidity by gender or age
      group, affective subtype or prevalence period. The onset of anxiety disorders
      generally preceded that of depression, whereas alcohol misuse was equally likely
      to pre-or post-date the onset of affective disorders. Finally, comorbidity was
      associated with an elevation in treatment rates across all sites, confirming
      Berkson's paradox on an international level.

PMID- 8864151
TI  - Major depression and generalised anxiety disorder. Same genes, (partly)different
      environments--revisited.
AB  - In both clinical and epidemiological samples, major depression (MD) and
      generalised anxiety disorder (GAD) display substantial comorbidity. In a prior
      analysis of lifetime MD and GAD in female twins, the same genetic factors were
      shown to influence the liability to MD and to GAD. A follow-up interview in the
      same twin cohort examined one-year prevalence for MD and GAD (diagnosed using a
      one-month minimum duration of illness). Bivariate twin models were fitted using
      the program Mx. High levels of comorbidity were observed between MD and GAD. The
      best-fitting twin models, when GAD was diagnosed with or without a diagnostic
      hierarchy, found a genetic correlation of unity between the two disorders. The
      correlation in environmental risk factors was +0.70 when GAD was diagnosed non
      hierarchically, but zero when hierarchical diagnoses were used. Our findings
      provide further support for the hypothesis that in women, MD and GAD are the
      result of the same genetic factors. Environmental risk factors that predispose to
      'pure' GAD episodes may be relatively distinct from those that increase risk for
      MD.

PMID- 8864152
TI  - Comorbidity and the general neurotic syndrome.
AB  - The observation that people with an anxiety or depressive disorder also have an
      increased likelihood of having had other anxiety or depressive disorders in their
      lifetime means either that the separate causes of these disorders have
      aggregated, much more than chance would allow, or that some general vulnerability
      factor has made them liable to each and all of the disorders they report. In this
      paper, three separate sources of information-symptoms occurring in the general
      population, disorders occurring in the general population, and disorders
      occurring in patients who have sought treatment-are reviewed. In all three
      domains of information, a general vulnerability factor, associated with
      personality trait measures of high trait anxiety and poor coping, emerges as a
      principal cause of these symptoms or disorders, and accounts for the majority of
      the variation in the comorbidity of symptoms or disorders. This vulnerability
      factor is shown to be under substantial gentic control. Nevertheless it can be
      modified by appropriate treatment, and prevention strategies exist to reduce the
      incidence of the anxiety and depressive disorders.

PMID- 8864153
TI  - Implications of comorbidity for genetic studies of bipolar disorder: P300 and eye
      tracking as biological markers for illness.
AB  - In large families with affective illness, identification of a biological variable
      is needed that reflects brain dysfunction at an earlier point than symptom
      development. Eye movement disorder, a possible vulnerability marker in
      schizophrenia, is less clearly associated with affective illness, although a
      subgroup of affective disorders shows smooth-pursuit eye movement disorder. The
      auditory P300 event-related potential may be a useful marker for risk to
      schizophrenia, but a role in bipolar illness is less certain. The distribution of
      these two biological variables and their association with symptoms in two
      multiply affected bipolar families is described. In a single, five-generation
      family identified for linkage studies through two bipolar I (BPI) probands, 128
      members (including 20 spouses) were interviewed. The 108 related individuals had
      diagnoses of BPI (7), bipolar II (2), cyclothymia (3), or major depressive
      disorder (19). Eight others had generalised anxiety (1), minor depression (5),
      intermittent depression (1), or alcoholism (1). Sixty-nine subjects had no
      psychiatric diagnosis. P300 latency (81) and eye tracking (71) were recorded from
      a subgroup of relatives within the pedigree. Eye tracking was abnormal in 11 of
      71 relatives (15.5%) and was bimodally distributed. In these 11 relatives,
      clinical diagnoses included minor depression (1), alcoholism (1) and generalised
      anxiety disorder (1). P300 latency was normally distributed and did not differ
      from controls. In a second family in which five of seven siblings have BPI
      illness, P300 latency and eye movement disorder were found in affected relatives
      and in some unaffected offspring. In these large families, clinical diagnoses of
      general anxiety, alcoholism and minor depression, when associated with eye
      tracking abnormality, may be considered alternative clinical manifestations of
      the same trait that in other relatives is expressed as bipolar illness.

PMID- 8864154
TI  - Co-occurrence and contransmission of affective disorders and alcoholism in
      families.
AB  - The analysis of patterns of co-occurrence and cotransmission of affective
      disorders and alcoholism in families may provide clues for understanding the
      excess comorbidity between these conditions in clinical settings and in the
      general population. This paper reports the results of a family study of the
      relatives of patients with bipolar disorder, unipolar depression and alcoholism,
      and combinations thereof. Excess comorbidity between affective disorders and
      alcoholism was observed in all groups of relatives. However, the sharing of
      familial aetiological components was not a major contributor to the excess
      comorbidity between affective disorders and alcoholism. Unipolar depression and
      alcoholism segregated independently in families, whereas a modest correlation
      between familial components of alcoholism and bipolar disorder was observed.

PMID- 8864155
TI  - The relationship between pain and depression.
AB  - Empirical results from epidemiological studies on pain-depression comorbidity in
      primary care and population samples have shown that: (a) pain is as strongly
      associated with anxiety as with depressive disorders; (b) characteristics that
      most strongly predict depression are diffuseness of pain and the extent to which
      pain interferes with activities; (c) certain psychological symptoms (low energy,
      disturbed sleep, worry) are prominent among pain patients, while others (guilt,
      loneliness) are not; (d) depression and pain dysfunction are evident early in the
      natural history of pain, but dysfunction and distress are often transient; and
      (e) among initially dysfunctional pain patients whose dysfunction is chronic,
      depression levels do not improve but neither do they increase over time with
      chronicity alone. These results seem consistent with these mechanisms of pain
      depression comorbidity; (1) a trait of susceptibility to both dysphoric physical
      symptoms (including pain) and psychological symptoms (including depression), and
      a state of somatosensory amplification in which psychological distress amplifies
      dysphoric physical sensations (including pain); (2) psychological illness and
      behavioural dysfunction being interrelated features of a maladaptive response to
      pain evident early in the natural history of the condition, and often resolving
      during an early recovery phase; (3) pain constituting a significant physical and
      psychological stressor that may induce or exacerbate psychological distress.
      Thus, pain and psychological illness should be viewed as having reciprocal
      psychological and behavioural effects involving both processes of illness
      expression and adaption, as well as pain having specific effects on emotional
      state and behavioural function.

PMID- 8864156
TI  - Cancer and depression.
AB  - Half of all cancer patients have a psychiatric disorder, usually an adjustment
      disorder with depression. Anxiety about illness, such as cancer, often leads to
      delay in diagnosis, which has been estimated to reduce prospects of long-term
      cancer survival by 10% to 20%. Although earlier studies showed that depressed
      individuals were at higher risk for cancer incidence, later studies have not
      confirmed this predictive relationship. Nonetheless, effective psychotherapeutic
      treatment for depression has been found to affect the course of cancer.
      Psychotherapy for medically ill patients results in reduced anxiety and
      depression, and often pain reduction. In three randomised studies, psychotherapy
      resulted in longer survival time for patients with breast cancer (18 months),
      lymphoma, and malignant melanoma. The physiological mechanisms for these findings
      have not yet been determined, but four fundamental possibilities for
      psychotherapeutic effects on physiological change include health maintenance
      behaviour, health-care utilisation, endocrine environment, and immune function.
      Thus, effective treatment of depression in cancer patients results in better
      patient adjustment, reduced symptoms, reduced cost of care, and may influence
      disease course. The treatment of depression in these patients may be considered a
      part of medical as well as psychiatric treatment.

PMID- 8864157
TI  - Depressive syndromes and symptoms in subjects with human immunodeficiency virus
      (HIV) infection.
AB  - The association between the infection produced by the human immunodeficiency
      virus (HIV) and syndromal or subsyndromal depression has been the topic of
      several studies in recent years. The results of the WHO Neuropsychiatric AIDS
      Study, conducted in the five geographical areas predominantly affected by the HIV
      epidemic, suggest that the symptomatic stages of HIV infection are associated
      with an increased prevalence of depressive symptoms, and, at least in some
      contexts in which the spreading of the infection is more recent and the social
      rejection of HIV-seropositive subjects is harsher, may also be associated with an
      increased prevalence of a syndromal diagnosis of depression.

PMID- 8864158
TI  - Depression and endocrine disorders: focus on the thyroid and adrenal system.
AB  - Of the various hypothalamic-pituitary-end organ axes, the thyroid and adrenal
      systems have been implicated most often in affective disorders. Patients with
      primary thyroid disease have high rates of depression, and patients with
      Addison's disease or Cushing's syndrome have relatively high rates of affective
      and anxiety symptoms. However, the major support for these endocrine axes in the
      pathophysiology of mood disorders comes from studies in which alterations in
      components of the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic
      pituitary-adrenal (HPA) axes have been documented in patients with primary
      depression. Concerning the HPT axis, depressed patients have been reported to
      have: (a) alterations in thyroid-stimulating hormone response to thyrotropin
      releasing hormone (TRH); (b) an abnormally high rate of antithyroid antibodies;
      and (c) elevated cerebrospinal fluid (CSF) TRH concentrations. Moreover, tri
      iodothyronine has been shown conclusively to augment the efficacy of various
      antidepressants. Concerning the HPA axis, depressed patients have been reported
      to exhibit: (a) adrenocorticoid hypersecretion; (b) enlarged pituitary and
      adrenal gland size; and (c) elevated CSF corticotropin-releasing factor
      concentrations. All of the HPA axis alterations in depression studied thus far
      are state-dependent, whereas the HPT axis alterations may be partially trait and
      partially state markers.

PMID- 8864159
TI  - Comorbidity (psycho) analysed.
AB  - Many psychiatric patients seem to suffer from a multitude of psychiatric
      disorders. The term 'comorbidity' was introduced to characterise that situation.
      This term, however, is multi-interpretable and thus conceals more than it
      clarifies. Five interpretations of the concept of comorbidity are discussed, in
      conjunction with the consequences their validity would have for psychiatric
      research, in particular for the biological branch. If the term comorbidity
      continues to be used without further qualification, it will slow down the process
      of conceptualization of novel research strategies in experimental psychiatry,
      which is so urgently needed.

PMID- 8864160
TI  - A teratologist to extinction. Ad Hoc Committee on Grant Funding.

PMID- 8864161
TI  - A teratologist to extinction.

PMID- 8864162
TI  - Problems in teratology research.

PMID- 8864163
TI  - Hydroxamic acid: a potential human teratogen that could be recommended to treat
      ureaplasma.
AB  - Hydroxamic acid has been shown in experimental animals to be teratogenic. It can
      be used to treat chronic cervicitis; extreme caution is recommended to avoid
      exposure to this potential human teratogen.

PMID- 8864164
TI  - Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol
      during gestation.
AB  - The most serious features of fetal alcohol syndrome (FAS) are mental retardation
      and other behavioral problems resulting from alcohol-induced damage to the
      developing central nervous system (CNS). The mechanism by which alcohol induces
      its neuroteratogenic effects is unknown. One hypothesis is that gestational
      alcohol exposure results in a reduction in neuronal number. This study
      demonstrates that gestational exposure to ethanol in a non-human primate species
      induces permanent dose-related deficits in the number of cerebellar Purkinje
      cells. Ethanol was administered via nasogastric tube once per week to 15 gravid
      pigtailed macaques (Macaca nemistrina) in one of the following doses: 0.0
      (intubated controls), 1.2, 1.8, 2.5, 3.3, and 4.1 g/kg/dose. Offspring were
      reared with parental surrogates and were sacrificed at 6 months of age; 8-microns
      thick, parasagittal sections were cut through the paraffin-embedded cerebellar
      vermis. Purkinje cells were quantified, the length of the Purkinje cell line was
      determined stereologically, and Purkinje cell linear frequency was calculated.
      The number of Purkinje cells and their linear frequencies were significantly
      reduced in the alcohol-treated subjects, and the deficits were dose-dependent.
      The groups receiving 2.5 g/kg/dose and above were most severely affected and had
      an average deficit in Purkinje cell number of 11.8%, relative to controls.
      Alcohol had no effect on the length of the Purkinje cell line. The findings
      suggest that alcohol-induced reduction in neuronal number may be an important
      factor underlying the CNS dysfunction in FAS.

PMID- 8864165
TI  - Comparative embryolethality and teratogenicity of the all-trans isomers of
      retinoic acid, 3,4-didehydroretinyl acetate, and retinyl acetate in pregnant
      rats.
AB  - The teratogenic potencies of the all-trans isomers of retinoic acid (RA), 3,4
      didehydroretinyl acetate (A2), and retinyl acetate (A1) were compared. Groups of
      eight timed-pregnant Sprague-Dawley rats were administered single equimolar doses
      (3.5-352 mumol/kg BW) of the retinoids orally in oil on day 8.5 of pregnancy, and
      dams and fetuses were sacrificed on day 19. The relative teratogenicity and
      embryolethality of the three tested retinoids were: RA > A2 > A1. The no-effect
      level of RA and A2 was 3.5 mumol/kg BW and of A1 was 35 mumol/kg BW. Whereas the
      adverse effects of RA and A1 were dose dependent, A2 showed biphasic effects,
      with a peak of embryolethality at 35 mumol/kg BW. Dams also exhibited weight loss
      and other toxic manifestations from doses of A2 and Ra > or = 35 mumol/kg BW. In
      dosed dams, (1) Liver concentrations of A1 and A2 increased with the doses of A1
      and A2, respectively, (2) RA had little effect on liver A1 except for an increase
      at the highest toxic dose, and (3) A2 showed a sparing effect on liver A1. RA,
      although not detected in fetuses from dams treated with A1, was present in
      significant concentrations (0.5-4.1 nmol/g liver) in fetuses from dams treated
      with A2. The biphasic change in embryolethality with the dose of A2 correlates
      with this enhanced concentration of fetal RA. We hypothesize that the actual
      teratogen in the fetuses of A2-dosed dams is RA. A2 might induce this biphasic
      effect by inhibiting the catabolism of RA at lower doses and its formation at
      higher doses.

PMID- 8864166
TI  - Toxicokinetic analysis of losartan during gestation and lactation in the rat.
AB  - Previous developmental and reproductive toxicity studies in rats with losartan, a
      potent AT1-selective angiotensin II (AII) receptor antagonist, correlated
      maternal treatment during gestation day (GD) 15-20 with irreversible renal
      abnormalities in the F1 generation (Spence et al., '95a,b). Continued treatment
      through lactation was also associated with increases in pup mortality and
      decreases in pup body weights that persisted through weaning. The studies
      presented here were undertaken to quantify fetal and neonatal exposure to
      losartan when administered to the dam by oral gavage during early gestation, late
      gestation, and lactation. Following daily oral dosing of 135 mg/kg/day on GD6-15,
      fetal drug levels were negligible. However, losartan and its active metabolite,
      EXP3174 (L-158,641) were readily detectable in fetal plasma on GD 20 (estimated
      AUC values, 50.70 and 167.70 micrograms/hr/ml, respectively) and maternal milk
      during lactation (1.61 and 1.67 micrograms/ml, respectively). These studies
      suggest that the relative increased sensitivity of the fetus as compared to the
      neonate for losartan-induced renal lesions is related to the degree of exposure
      which is dependent on the time of administration (early gestation vs. late
      gestation/lactation) and the route of exposure (transplacental or through the
      milk). Furthermore, the maximum exposure to losartan and EXP3174 correlates with
      the ontogeny of the renin angiotensin system on approximately GD 17 and the
      critical period for losartan-induced renal lesions (GD15-20). The data support
      the hypothesis that the observed adverse fetal and neonatal effects are
      pharmacologically mediated, presumably through the lack of AT1 receptor
      stimulation.

PMID- 8864167
TI  - Anencephaly, dorsal hypermelia, and duplication of the vertebral column: a rare
      type of rachipagus conjoined twins.
AB  - The rare combination of hypermelia with craniorachischisis and duplication of the
      vertebral column has been found in three cases, two published and one previously
      unreported. Even though the previous authors had come to other conclusions,
      careful analysis of the details in these twins leads to the inescapable
      conclusion that they were all dorsally united parasitic rachipagus twins. The
      nature of the original union was clearly indicated by (1) the articulation of
      autositic ribs to two different vertebral columns but to a single ventral
      sternum, (2) the articulation of parasitic ribs also to the two vertebral columns
      but fusion of the ribs and clavicles dorsally without an interposed sternum, and
      (3) the dorsal location of the rudimentary viscera of the parasite. The
      orientation of notomelic arms was confirmatory but not diagnostic. The proposed
      embryologic origin of these twins is presented.

PMID- 8864168
TI  - Parental cigarette smoking and risk for congenital anomalies of the heart, neural
      tube, or limb.
AB  - Risks for selected congenital anomalies from parental smoking were investigated
      in a case-control study in California. Mothers of 207 infants with conotruncal
      heart defects, 264 infants with neural tube defects, 178 infants with limb
      deficiencies, and 481 live born control infants delivered in 1987-1988 were
      interviewed by telephone. Modestly elevated risks were observed for conotruncal
      heart defects and limb deficiencies, associated primarily with both parents
      smoking. An odds ratio of 1.9 (95 percent confidence interval 1.2-3.1) was
      observed for conotruncal heart defects and an odds ratio of 1.7 (95% confidence
      interval 0.96-2.9) for limb deficiencies when both parents smoked compared to
      neither parent smoking. We did not observe increased risks associated with
      maternal smoking in the absence of paternal smoking, although an increased risk
      associated with paternal smoking in the absence of maternal smoking was observed
      for limb deficiencies in offspring. For conotruncal defects, the risks associated
      with parental smoking differed among race/ethnic groups. Parental smoking was not
      associated with increased risks for neural tube defects. Observed risks did not
      change substantially when adjusted for maternal vitamin use, alcohol use, and
      gravidity. Some heterogeneity in risk was observed for phenotypic case subgroups,
      but data were too sparse to draw firm inferences.

PMID- 8864169
TI  - A comparison of three statistical models for IDDM associations with HLA.
AB  - The association between HLA-DQ haplotypes and insulin-dependent diabetes mellitus
      (IDDM) was studied in 48 children from 44 families ascertained from the high
      incidence area around Umea, Sweden. Numerous hypotheses have been proposed to
      explain associations between HLA and IDDM, but comparisons of statistical models
      based on these hypotheses have not been attempted. The aim of the present study
      was to compare the goodness-of-fit and predictive abilities among different
      statistical models. A likelihood-based analysis rather than a conventional
      analysis based on contingency tables was therefore adopted. We first used
      parental haplotype information in a conditional likelihood analysis (1) and then
      compared this analysis with that of an unaffected control group which used
      information on geographically matched controls. Under the analysis conditional on
      parental haplotype, a statistical model motivated by the hypothesis that the
      entire DQ heterodimer is involved in IDDM pathogenesis fit the data significantly
      better and had greater predictive ability than either a model motivated by the
      explanation that an IDDM gene is linked to DQB1 or that the DQB1 chain itself is
      involved in IDDM pathogenesis, or a model arising from the hypothesis that single
      amino acids at codon 57 of DQB1 and codon 52 of DQA1, respectively, confer
      susceptibility. Under the case-control analysis, the identity of the best-fitting
      or more predictive statistical model was not as clear, although both approaches
      to analyzing risk suggested that the single-amino-acids model had significantly
      poorer fit compared to the remaining two models.

PMID- 8864170
TI  - Expression of LA45 reactive beta 2-microglobulin free HLA class I alpha-chains on
      activated T-cells is regulated by internalization, constitutive and protein
      kinase C inducible release.
AB  - HLA Class I molecules on activated T cells are expressed as mAb W6/32 reactive
      heterodimers associated with beta 2-microglobulin (beta 2-m) and also as mAb LA45
      reactive beta 2-m free HLA Class I alpha-chains. However, the regulation of free
      alpha-chain expression remained enigmatic. Here we show, that the amount of cell
      surface expressed free heavy chains is influenced by two distinct mechanisms.
      Firstly, a proportion of expressed molecules are cleaved and give rise to a
      soluble pool of HLA Class I molecules. We provide evidence that, besides the
      previously described constitutive release of free alpha chains, a second phorbol
      ester inducible release mechanism involving activation of protein kinase C (PKC)
      does exist. We demonstrate that both the constitutive and the enhanced release of
      LA45 reactive HLA Class I alpha-chains are the consequence of a cell membrane
      bound proteolytic activity with the characteristics of a 1, 10 phenanthroline
      sensitive metalloprotease. Secondly, we report that a distinct fraction of mAb
      tagged free alpha-chains is internalized via an n-ethylmaleimide sensitive
      pathway. Together, this data suggests that the expression of free alpha-chains is
      regulated by pathways governing release and internalization.

PMID- 8864171
TI  - Tumor associated antigens in human renal cell carcinoma: MHC restricted
      recognition by cytotoxic T lymphocytes.
AB  - Based on previous studies in human melanoma leading to the molecular cloning of
      genes encoding peptide antigens recognized by MHC-restricted cytotoxic T
      lymphocytes (CTL) we extended our efforts to renal cancer systems established in
      tissue culture. In two patients we obtained stable CD8+ CTL clones with high
      cytolytic activity for the corresponding autologous tumor cell line in vitro.
      Neither autologous EBV-transformed B lymphocytes or PHA-activated PBL nor natural
      killer targets K562 were lysed by these CTL clones. MZ1257-RCC CTL5-30 lysed
      autologous tumor cells as well as normal kidney cell cultures in an HLA-A2
      restricted fashion. Further specificity analysis showed cross reactivity with HLA
      A2 matched renal cancer cell lines, melanoma cell lines and tumor cell lines of
      other origins. HLA-A2 negative target cells were not lysed. The restriction
      element for T cell recognition in another renal cancer system, MZ1973-RCC,
      appeared to be HLA-B8 as tested with CTL 5-10. Crossreactivity of CTL 5-10 was
      documented with one HLA-B8 positive RCC line. Tumor cell lines of other origin
      were not lysed by CTL 5-10. For further study of CTL-defined epitopes, peptides
      were extracted from tumor cell lines. Peptides from cultured cell lines were acid
      eluted and fractionated by reversed phase HPLC. The peptide fractions were tested
      in cytotoxicity assays for their ability to reconstitute RCC epitopes by addition
      to the HLA-A2.1 positive antigen processing mutant cell line 721.124xCEM.T2. One
      HPLC peak was identified containing an epitope for the HLA-A2 restricted MZ1257
      RCC CTL 5-30. These peptide epitopes were present in the autologous renal cancer
      cell line MZ1257-RCC as well as in an allogeneic HLA-A2 positive RCC cell line
      MZ1973 and melanoma cell line SK29-MEL, but were absent in peptides eluted from
      autologous EBV-B cells. We conclude that renal cell carcinoma may induce
      autologous CTL. Epitopes recognized by MHC-restricted CTL on RCC may be shared by
      HLA-matched allogeneic renal cancer or even tumors of other origin, such as
      melanoma. The current challenge is the determination of the amino acid sequences
      of these CTL-defined peptides as a step to further characterize the nature of
      these tumor associated antigens.

PMID- 8864172
TI  - HLA DQ-DR haplotype and susceptibility to cervical carcinoma: indications of
      increased risk for development of cervical carcinoma in individuals infected with
      HPV 18.
AB  - The association of HLA class II DQB1 and DRB1 alleles with the development of
      cervical carcinoma was studied in 150 Swedish patients using PCR-based HPV and
      HLA typing. The association of cervical carcinoma with alleles encoding the DQ3
      antigen, previously found among German and Norwegian patients, was not observed
      in the Swedish patients. Five DQ-DR haplotypes were indicated to be positively
      associated with development of cervical carcinoma in the Swedish patients. Two of
      these HLA associations were specific for HPV 18 infected patients, suggesting
      that the ability of the oncogenic HPV 18 to cause more rapid-transit tumors than
      other high risk HPV types may be due to a deficiency in antigen presentation by
      the HLA molecules encoded by carried on these haplotypes.

PMID- 8864173
TI  - Development and characterization of rabbit antisera to human MHC-linked
      transporters associated with antigen processing.
AB  - The limited availability of sera to human MHC-linked transporters associated with
      antigen processing (TAP) has hampered the analysis of the role of these molecules
      in the reduced HLA Class I antigen expression by normal and transformed cells. To
      overcome these limitations, anti-human TAP1 and anti-human TAP2 xenoantisera have
      been generated and characterized. To this end rabbits have been immunized with
      TAP1-specific or TAP2-specific peptides which correspond to nonhomologous,
      hydrophilic regions of each transporter subunit. The immunized rabbits developed
      high titer IgG antibodies which displayed specific reactivity with the immunizing
      peptides in ELISA. Both anti-TAP1 and anti-TAP2 antisera immunoprecipitated the
      70-76 kDa TAP complex from TAP(+)-TAP2+ cell lines WALK and Colo 38, but
      precipitated no component from TAP(-)-TAP2- cell lines T2 and SK-MEL-19.
      Furthermore, in immunodepletion experiments anti-TAP1 and anti-TAP2 antisera
      removed the molecules recognized by each of them in a lymphoid cell extract.
      Lastly, in Western blotting assays anti-TAP1 and anti-TAP2 antisera reacted
      specifically with isolated TAP1 and TAP2, respectively. The latter results in
      conjunction with those of the immunodepletion experiments indicate that TAP1 and
      TAP2 are not detectable as isolated subunits in a cell extract and that TAP
      heterocomplex is the major, if not the only detectable molecular species in
      cells. Anti-TAP1 and anti-TAP2 antisera were evaluated in immunohistochemical
      staining of both frozen and formalin fixed sections of skin and primary malignant
      melanoma lesions. Both antisera stained the cytoplasm of keratinocytes in normal
      skin and of melanoma cells in malignant lesions. The antisera we have elicited
      with TAP1- and TAP2-specific peptides appear to be useful reagents to
      characterize the role of TAP in abnormalities of HLA Class I antigen expression.

PMID- 8864174
TI  - A functional monoclonal antibody recognizing the human alpha 1-integrin I-domain.
AB  - Alpha 1 beta 1 heterodimer is a member of the integrin receptor superfamily that
      has been described to be involved in cell-matrix binding through its interaction
      with collagens, fibronectin and laminin. The alpha 1 integrin belongs to a subset
      of I-domain containing integrins that includes alpha M, alpha L, alpha X and
      alpha 2. In this study we describe an anti-alpha 1 mAb (FB12) that recognizes an
      epitope located in the human alpha 1 I-domain, since the mAb can bind to human,
      but not to rat, recombinant I-domain GST fusion protein. FB12 mAb efficiently and
      specifically inhibits the binding of activated human lymphocytes to laminin,
      collagen and fibronectin. These data support the notion that the alpha 1 I-domain
      itself has an important role in receptor-ligand binding. In particular, we show
      that alpha 1 integrin-dependent lymphocyte adhesion to fibronectin is I-domain
      mediated, at variance with the RGD-dependent adhesion which seems to be mediated
      by the beta 1 rather than the alpha 1 integrin chain. Lastly, the overexpression
      of the alpha 1-integrin by stromal cells and blood vessels of solid tumors may
      suggest a role for this integrin in tumor biology.

PMID- 8864175
TI  - New DRB1*1120 allele; another example of the transition between the DR11 and DR13
      families of alleles.

PMID- 8864176
TI  - HLA-C genotyping in the Japanese population by the PCR-SSP method.

PMID- 8864177
TI  - The primate MHC contains sequences related to the fibroblast growth factor
      receptor gene family.
AB  - We have cloned and sequenced a genomic region centromeric of the HLA-B locus from
      different MHC ancestral haplotypes. These haplotypes are associated with several
      diseases. The sequences were analyzed for coding potential and their relevance to
      disease associations were assessed with respect to the level of polymorphism.
      Analysis of sequences located approximately 25kb centromeric of HLA-B reveals the
      existence of fibroblast growth factor receptor related sequences. These sequences
      designated PERB1 (FGFR6) reveal 80% homology, at both nucleic acid and amino acid
      level, to the immunoglobulin domain 1 (Ig-1) of the human fibroblast growth
      factor receptor 3 (FGFR3) gene. Amino acid comparison of the Ig-1 domain of PERB1
      to those of other FGFR molecules indicates that PERB1 is more closely related to
      FGFR3 and FGFR5 than to FGFR1, FGFR2 or FGFR4. Genomic sequence analysis,
      however, reveals no consensus splice sites and indicates the existence of inframe
      premature stop codons in the putative coding sequences. The results suggest that
      these sequences may represent FGFR gene fragments existing within the central
      MHC. Sequence analysis of the Mhc in 6 chimpanzee and one orangutan indicates
      that the existence of PERB1 predates the speciation of the three species. The
      fact that the MHC contains a mixture of functional and nonfunctional (pseudo)
      genes suggests that a functional copy of PERB1 (FGFR6) may exist within or in
      close proximity to the MHC.

PMID- 8864179
TI  - Nomenclature for factors of the HLA system, update April 1996.

PMID- 8864178
TI  - CD69 expression on primitive progenitor cells and hematopoietic malignancies.
AB  - CD69 is an early activation antigen of peripheral blood lymphocytes and is
      constitutively expressed on a wide variety of bone marrow-derived cells. To
      further characterize the distribution and understand the potential biological
      role of the molecule in normal and malignant hematopoiesis, we used a novel high
      affinity anti-CD69 mAb (UN6) and analyzed hematopoietic progenitor cells together
      with a panel of myeloid and lymphoid malignancies. We report that mobilized
      peripheral blood CD34+ cells display detectable levels of CD69 and that the
      density of membrane expression correlates with the immature phenotype CD34bright
      Thy-1bright cells. Furthermore, during cytokine-induced differentiation, the
      expression of CD69 is moderately down-regulated. Analysis of hematopoietic
      malignancies revealed that CD69 expression correlates with the immature myeloid
      phenotype. Taken together these data suggest a role of CD69 during the early
      phase of hematopoiesis and in the leukemic transformation.

PMID- 8864180
TI  - Recombinant human interleukin-3 induces extramedullary hematopoiesis at
      subcutaneous injection sites in cynomolgus monkeys.
AB  - Parenteral administration of recombinant hematopoietic growth factors has been
      sporadically associated with cutaneous complications, including injection site
      reactions in humans and nonhuman primates. In this study, subcutaneous injection
      sites were evaluated from 12 cynomolgus monkeys administered a recombinant human
      interleukin-3 (rhIL-3) at dose levels of 0, 70, or 700 micrograms/kg daily for 18
      days. Monkeys administered rhIL-3 developed small (0.5-1-cm-diameter), firm
      nodules at the subcutaneous injection sites. Histologically, these nodules from 4
      of 8 rhIL-3-treated monkeys contained trilineage extramedullary hematopoiesis
      (EMH) represented by precursors of myeloid, erythroid, and megakaryocytic series
      cells. The lineage of hematopoietic cells was confirmed by histochemical and
      immunohistochemical methods. Hematopoietic cells of myeloid and megakaryocytic
      lineages were more common than erythroid cells. Of myeloid cells, immature
      eosinophils were more common, which usually formed small sheets or clusters in
      the panniculus and deep dermis. This report describes, for the first time, the
      occurrence of cutaneous EMH at the injection sites of recombinant hematopoietic
      growth factors, which should be differentiated from inflammation. We believe the
      cutaneous EMH was the exaggerated pharmacologic effect of rhIL-3.

PMID- 8864181
TI  - Long-lasting effect of dexrazoxane against anthracycline cardiotoxicity in rats.
AB  - The long-lasting protective effect of dexrazoxane (ADR-529) against doxorubicin-
      and epirubicin-induced cardiotoxicity was evaluated in the multiple-dose 35-wk
      rat model. Groups of 36 male Sprague-Dawley rats were given ADR-529 30 min before
      administration of cardiotoxic doses of doxorubicin (1 mg/kg/wk) or epirubicin
      (1.13 mg/kg/wk). The compounds were intravenously injected once weekly for 7
      consecutive wk at ADR-529; anthracycline ratios ranging from 5:1 to 20:1. These
      ratios covered the entire chemotherapeutic range in humans and allowed studying
      the chronic progressive cardiomyopathy in our rat model. Animals were observed
      for up to 35 wk to follow the time course of the well-characterized
      cardiomyopathy, which was evaluated through the well-established
      qualitative/quantitative morphological grading. It was clearly demonstrated in
      this rat model that ADR-529, at the ratios administered, provided ample
      cardioprotection for a duration of 35 wk, which corresponds to 25 yr of
      equivalent human time.

PMID- 8864182
TI  - Light microscopic comparison of surfactant-induced eye irritation in rabbits and
      rats at three hours and recovery/day 35.
AB  - Limited information exists on the pathologic changes occurring with surfactant
      induced ocular irritation in the context of accidental human exposures and animal
      tests used to assess for such irritation. The purpose of this study was to begin
      to characterize the pathologic changes that occur with surfactants in the context
      of standard animal tests and compare the response in rats to that in rabbits.
      Representative anionic, cationic, and nonionic surfactants causing slight to
      severe ocular irritation were directly applied to the corneas of rabbits and rats
      at a dose of 10 microliters. Eyes and eyelids of each animal were macroscopically
      examined for signs of irritation beginning 3 hr after dosing and periodically
      until recovery or day 35. Eyes and eyelids from animals in each group were
      collected for microscopic examination after 3 hr and at recovery or day 35.
      Microscopically, all of the surfactants caused erosion, denudation, and/or
      necrosis of the conjunctival and corneal epithelium in rabbits and rats. Necrosis
      of keratocytes was observed in rabbits and rats treated with the severely
      irritating cationic surfactant and in rats treated with anionic surfactants that
      were mildly irritating and moderately irritating. Corneal endothelial changes
      were observed in rabbits and rats with only the cationic surfactant. Changes in
      eyes of rabbits and rats that had not recovered by day 35 included decreased
      prominence of goblet cells, conjunctivalization of the corneal epithelium,
      neovascularization and fibrosis of the cornea, and presence of devitalized
      stroma. Overall, the changes in rabbits and rats were similar and suggest that
      the rat may be used as a surrogate for the rabbit in studies to understand better
      mechanisms of surfactant-induced eye irritation.

PMID- 8864183
TI  - Application of in vivo confocal microscopy to the understanding of surfactant
      induced ocular irritation.
AB  - The purpose of this study was to assess the ability of in vivo confocal
      microscopy (CM) to provide noninvasively derived histopathologic correlates of
      surfactant-induced eye irritation from which specific pathologic mechanisms can
      be identified and later evaluated in alternative in vitro models. Rats and
      rabbits, divided into groups of 5, received 10 microliters of an anionic or
      cationic surfactant in one eye with the other eye used as a control. At specified
      times, eyes were examined and scored for ocular irritancy using a penlight and
      slit-lamp. Subsequently, corneas were evaluated by in vivo CM to evaluate
      epithelial layer thickness and surface epithelial cell area, corneal thickness,
      depth of necrosis, inflammation, fibrosis, and endothelial injury. At 3 hr, the
      anionic surfactant produced slight irritation with peak scores of 12.4 and 8.0
      out of a possible 110 in the rats and rabbits, respectively. In vivo CM revealed
      changes limited to the corneal epithelium that decreased in thickness to 78% in
      rats and 81% in rabbits at 3 hr. This decrease in the thickness correlated with a
      significant decrease in surface epithelial cell area from 2,061 +/- 395 microns2
      to 567 +/- 330 microns2 in the rats and 1,523 +/- 185 microns2 to 934 +/- 71
      microns2 in the rabbits (p < 0.005 and 0.005, respectively). The cationic
      surfactant produced severe irritation in both the rats and rabbits with peak
      scores of 85.4 and 80.2 occurring at day 2, respectively. In vivo CM in the rats
      showed complete loss of corneal epithelium, lysis of keratocytes, and loss of
      corneal endothelium. In the rabbits, injury appeared limited to the anterior
      cornea with complete loss of epithelium and loss of keratocytes extending to 52%
      of the corneal thickness. These findings establish the application of
      noninvasive, in vivo CM to qualitatively and quantitatively characterize the
      pathobiology of ocular irritation in situ. This information will be important in
      the development and evaluation of mechanistically based in vitro alternatives for
      ocular irritancy testing.

PMID- 8864184
TI  - Characterization of coronary arterial lesions in the dog following administration
      of SK&F 95654, a phosphodiesterase III inhibitor.
AB  - Drugs that inhibit the low-Km, cGMP-inhibitable form of phosphodiesterase III
      (PDE III) are associated with arterial lesions in the extramural coronary
      arteries of dogs following oral and intravenous administration at high doses.
      Acute coronary arterial lesions have been investigated following administration
      to the dog of SK&F 95654, a potent PDE III inhibitor, and the progression of the
      lesion defined. Groups of 3 male beagle dogs received a single 2-hr infusion of
      SK&F 95654 at 8 mg/kg/hr and the characteristics of the coronary arterial lesions
      were evaluated at 1, 3, 10, and 34 days postdosing by light, scanning, and
      transmission electron microscopy. At 24 hr postdosing, the arterial lesion was
      characterized by segmental or circumferential necrosis of medial smooth muscle
      cells and hemorrhage; adventitial hemorrhage was also noted, particularly in the
      right atrial artery. Ultrastructural evaluation showed extensive medial necrosis,
      characterized by loss of smooth muscle cells and their replacement by cellular
      debris with ingress of erythrocytes, platelets, and inflammatory cells into the
      media. Associated with medial changes, significant endothelial effects were
      observed consisting of widening of intercellular boundaries, loss of normal
      elongated cellular appearance, and the attachment of numerous leukocytes and
      platelets. During the 10-34-day postdosing period, substantial repair of the
      arterial lesions occurred such that by day 34 all sections of extramural coronary
      artery were normal. The lesions induced in the dog are consistent with a
      hemodynamic effect induced by the pharmacological action of SK&F 95654.

PMID- 8864185
TI  - Mesenteric arteriopathy in the rat induced by phosphodiesterase III inhibitors:
      an investigation of morphological, ultrastructural, and hemodynamic changes.
AB  - A reproducible model of a phosphodiesterase III (PDE III) inhibitor-induced
      arteriopathy has been developed in the rat after subcutaneous administration of
      SK&F 95654. Administration of this potent PDE III inhibitor induced an
      arteriopathy of mesenteric arteries within 24 hr that was dose-related in
      intensity and incidence over the range 0.174, 0.348, 0.523, and 0.697 mmol/kg.
      The arteriopathy was restricted to muscular arteries of external diameter of 100
      800 microns and was shown microscopically to be focal or segmental medial
      necrosis and hemorrhage. A time-course experiment, conducted from 3 to 24 hr
      postdosing, showed that the first changes observed 6 hr postdosing were on the
      endothelium followed by focal hemorrhages into the media at 12 hr postdosing,
      causing compression, degeneration, and necrosis of myocytes. From 16 hr
      postdosing, there was focal endothelial cell necrosis and loss of confluence.
      Leukocytes and activated platelets were found adhering to exposed basement lamina
      and seen to pass through endothelial gaps into the subintima. By 24 hr
      postdosing, medial necrosis was extensive with large areas of media replaced by
      erythrocytes, cell debris, and a few leukocytes and platelets. The effect of 3
      structurally dissimilar PDE III inhibitors administered subcutaneously at a dose
      of 0.697 mmol/kg was compared with that of SK&F 95654. The arteriopathy induced
      by these compounds were identical to that produced by SK&F 95654 with the
      incidence and severity of lesions ranked in the following order: SK&F 95654 > WIN
      62582 > SK&F 94836, with no macroscopic lesions observed for SK&F 94120. Systolic
      blood pressure was measured for these 4 PDE III inhibitors at regular intervals
      over the 24-hr period postadministration by a plesthymographic method. The
      severity of the arterial lesions correlated with the magnitude of hypotension
      induced by these agents. It is postulated that the arterial damage is a
      consequence of profound vasodilation resulting in abnormal endothelial
      permeability and increased wall tension, resulting in progressive medial necrosis
      and hemorrhage.

PMID- 8864186
TI  - Cadmium-induced dental lesions in ovariectomized rats.
AB  - The effects of cadmium chloride on both incisor and molar teeth of ovariectomized
      female rats were studied histopathologically. The rats were injected
      intravenously with the compound at doses of 1.0 and 2.0 mg/kg, 5 days/wk. Six
      rats per group were sacrificed at 4, 8, and 13 wk. Discoloration of the incisors
      was observed in the rats of the 2.0-mg/kg group from 8 wk. Histopathologic
      examination of the incisor demonstrated decreased iron-containing pigment in
      ameloblasts and destruction of the enamel organ. These changes were accompanied
      with accumulation of cadmium and loss of iron in the teeth. Necrosis of the
      dental pulp occurred from the coronal end of both the incisor and molar teeth
      extended to the apical, deep portion of the teeth. The dental pulp of the molar
      teeth, which is shorter than that of the incisor, was mildly affected by cadmium
      intoxication. These findings suggested that intradental ischemia due to cadmium
      toxicity may have contributed to the development of the pulpal necrosis.

PMID- 8864187
TI  - Overexpression of cytochrome P-450 isoforms involved in aflatoxin B1
      bioactivation in human liver with cirrhosis and hepatitis.
AB  - Studies were carried out to test the hypothesis that inflammatory liver disease
      increases the expression of specific cytochrome P-450 isoenzymes involved in
      aflatoxin B1 (AFB) activation. The immunohistochemical expression and
      localization of various human cytochrome P-450 isoforms, including CYP2A6,
      CYP1A2, CYP3A4, and CYP2B1, were examined in normal human liver and liver with
      hepatitis and cirrhosis. The constitutive expression of CYP3A4 in normal liver
      showed a characteristic pattern of distribution in centrilobular hepatocytes,
      whereas CYP1A2, CYP2A6, and CYP2B1 were expressed uniformly throughout the liver
      acinus. In sections of liver infected with hepatitis B virus (HBV) or hepatitis C
      virus (HCV), the expression of CYP2A6 was markedly increased in hepatocytes
      immediately adjacent to areas of fibrosis and inflammation. CYP3A4 and CYP2B1
      were induced to a lesser degree, and expression of CYP1A2 was unaffected. In HBV
      infected liver, double immunostaining revealed that overexpression of CYP2A6
      occurred in hepatocytes expressing the HBV core antigen. In HCV-infected liver,
      CYP2A6, CYP3A4, and CYP2B1 were overexpressed in hepatocytes with hemosiderin
      pigmentation. These results suggest that alterations in phenotypic expression of
      specific P-450 isoenzymes in hepatocytes associated with hepatic inflammation and
      cirrhosis might increase susceptibility to AFB genotoxicity.

PMID- 8864188
TI  - Subchronic toxicity of atorvastatin, a hydroxymethylglutaryl-coenzyme A reductase
      inhibitor, in beagle dogs.
AB  - The toxicity of atorvastatin (AT), an inhibitor of hydroxymethylglutaryl-coenzyme
      A reductase (HMG), was evaluated in beagle dogs. In 4 studies [2-wk rising dose
      (daily increasing doses for 1 wk; maintenance for 1 wk), 12-wk rising dose (daily
      dosing with weekly increases in dose), 2-wk toxicity (daily dosing for 2 wk; 3
      dose levels), 13-wk toxicity (daily dosing for 13 wk; 3 dose levels)], dogs
      received up to 400 mg/kg orally. Doses of 180 mg/kg induced moribundity,
      necessitating euthanasia. Weight losses up to 26% were seen at doses > or = 150
      mg/kg. Decreases in cholesterol levels were dose-related. Alanine and/or
      aspartate aminotransferase were increased at doses > or = 80 mg/kg; alkaline
      phosphatase was increased at doses > or = 150 mg/kg. Histopathologic findings
      were seen at > or = 150 mg/kg and included hepatocellular eosinophilia related to
      increased smooth endoplasmic reticulum and cholangiohepatitis and cholecystitis
      at 150 mg/kg in the 2-wk toxicity study; hepatocellular degeneration,
      centrilobular bridging, cholecystitis, hemorrhage in gallbladder and brain,
      demyelination of optic nerve, and skeletal muscle necrosis at > or = 280 mg/kg in
      the 12-wk rising dose study; and erosion and hemorrhage in large intestine,
      hepatocellular degeneration and necrosis, and inflammation and necrosis of
      gallbladder epithelium at 320 mg/kg in the 2-wk rising dose study. Doses up to 80
      mg/kg for 13 wk did not induce histopathologic lesions in examined organs. AT
      effectively lowered serum cholesterol in normal lipidemic dogs. Toxicity at AT in
      dogs was similar to that with other inhibitors of HMG except that lenticular
      changes were not seen, significant hepatic, testicular, or neurological toxicity
      was associated only with high doses at AT, and skeletal muscle changes similar to
      those described in rats and rabbits were identified.

PMID- 8864189
TI  - The synovial membrane, liver, and tongue: target organs for a ricin A-chain
      immunotoxin (ZD0490).
AB  - ZD0490 is an immunotoxin consisting of a mouse monoclonal antibody conjugated to
      recombinant ricin A-chain (rRAC). It was developed at Zeneca Pharmaceuticals as a
      treatment for certain antigen-bearing tumors. During safety evaluation studies in
      rats, a number of reversible inflammatory changes were seen. The synovial
      membranes of articular joints showed a marked degeneration and necrosis with an
      associated inflammation. When of mild severity only the synovial membrane was
      involved, but when more severe many adjacent tissues including the surface of the
      articular cartilage were affected. Some nonspecific skeletal muscle toxicity
      occurred. However, tongues from the intravenously (tail) dosed rats consistently
      showed inflammation specifically located in the ventral subepithelial area with
      myocyte degeneration and necrosis. Also, hepatic peliosis primarily located in
      the subcapsular areas was induced. Studies with rRAC alone indicated that ricin A
      chain (RAC) is the component responsible for these findings. It is suggested that
      cells of a macrophage type with the ability to specifically bind RAC may at least
      in part determine the location and nature of the changes seen.

PMID- 8864190
TI  - A review of the hepatic tumors related to mixed-function oxidase induction in the
      mouse.
AB  - Mixed-function oxidase (MFO) induction in the mouse liver results in a rapid and
      sustained centrilobular hypertrophy associated with a hyperplastic response. In
      many studies, the long-term sequela of prolonged exposure is an increased
      incidence of lesions considered to be adenomas. Studies have shown in aged
      control mice that the burden of adenomas usually consists of lesions with
      basophilic cytoplasic staining and a uniform population of hepatocyte nuclei.
      With long-term feeding of MFO inducers, there is an additional burden of lesions
      diagnosed as adenomas having a different histological appearance with increased
      eosinophilic cytoplasm and pleomorphic nuclei. The incidence of hepatocarcinomas
      usually is not modified by the increased incidence of eosinophilic adenomas.
      Studies into the behavior of the eosinophilic lesions show that the hepatocytes
      approximate in their behavior to normal and not neoplastic cells. It is suggested
      that these lesions should not be considered a carcinogenic response to the
      chemical.

PMID- 8864191
TI  - Equivocal evidence of complete carcinogenicity after repeated infection of Syrian
      hamsters with Opisthorchis viverrini.
AB  - The effects of repeated infection with Opisthorchis viverrini on liver lesion
      development in male and female Syrian hamsters were investigated over a 1-yr
      period. Ten monthly intragastric applications of 50, 25, 13, or 0 parasite
      metacercariae resulted in pronounced proliferative and inflammatory lesions
      involving the first- and second-order ducts in response to the presence of adult
      worms. Despite the development of small numbers of putative preneoplastic areas
      of cholangiofibrosis and morphologically altered hepatocellular foci, no
      neoplastic lesions were evident at sacrifice after 1 yr. The results thus suggest
      that parasite infestation is itself not strongly carcinogenic if at all but,
      rather, that it exerts a marked promoting influence on cholangiocellular and
      hepatocellular tumor development in the hamster via chronic irritation and
      increased cell turnover.

PMID- 8864192
TI  - A case report of superficial necrolytic dermatitis in a beagle dog with diabetes
      mellitus.
AB  - A case of superficial necrolytic dermatitis in a young laboratory beagle dog with
      diabetes mellitus was investigated. Macroscopically, the skin lesion was
      restricted to paws showing erosion and swelling of the interdigital areas. The
      most predominant histopathological feature was upper-epidermal vacuolation of
      keratinocytes. In the pancreas, the number and size of islets were found to be
      markedly reduced, and only glucagon-positive cells were detected. In the liver,
      severe and widespread vacuolation of hepatocytes was observed. Blood biochemical
      assays showed that the serum glucose and plasma glucagon levels were increased.
      In addition, levels of individual amino acids varied markedly, although the total
      amino acid concentration was within the normal range. From these results, it was
      suggested that the skin lesion in this case was primarily caused by
      hyperglucagonemia in diabetes mellitus.

PMID- 8864193
TI  - A transgenic mouse prostate cancer model.

PMID- 8864194
TI  - Can so-called nongenotoxic hepatocarcinogens induce mouse liver nodules that are
      not neoplasms?

PMID- 8864195
TI  - Laboratory animal pathology--emphasis on an area of relevance to the toxicologic
      pathologist.

PMID- 8864196
TI  - The neoplastic potential of liver tumors induced by mixed-function oxidase
      inducers in the mouse.

PMID- 8864197
TI  - Validation of in vitro methods: societies' expectations require the involvement
      of toxicological pathologists.

PMID- 8864198
TI  - Third international conference on harmonization of technical requirements for
      registration of pharmaceuticals for human use--a toxicologist's perspective.
AB  - This overview provides a perspective on the ICH process and outcomes based on the
      third international conference held in Yokohama, Japan, in November/December
      1995. It is an attempt to provide awareness of this process to the toxicologic
      pathology community from the point of view of a practicing toxicologist and
      meeting attendee and to consolidate much of the information on this process in
      one place. The ICH process is an active, and ongoing process to improve the
      standardization of safety assessment testing throughout the world, and further
      changes will no doubt have occurred by the time this document is published.

PMID- 8864199
TI  - "Have you seen this?" Hypovolemic shock.

PMID- 8864200
TI  - Porcine adenoviruses types 1, 2 and 3 have short and simple early E-3 regions.
AB  - The nucleotide sequence of the E-3 region genes, the hexon associated protein
      pVIII genes, and part of the fiber genes coding for the N-terminal tail regions,
      of porcine adenovirus (PAV) types 1 and 2 were determined. The sizes of the E-3
      regions were found to be 1162 and 1222 bp, respectively. The five open reading
      frames (ORF) encoded within the sequenced regions of PAV types 1 and 2 shared a
      high degree of homology with the published sequences of the corresponding ORFs of
      PAV-3. The E-3 regions of PAV types 1, 2 and 3 were further characterized by
      Northern blot analysis and 5' and 3' end mapping of the transcripts by S1
      nuclease analysis. The results of these experiments indicated that the E-3
      regions in these three viruses are shorter and simpler in organization than the E
      3 regions of human adenoviruses. A potential promoter for the E-3 regions of
      these PAVs was identified.

PMID- 8864201
TI  - Equine herpesvirus-1 strain KyA, a candidate vaccine strain, reduces viral titers
      in mice challenged with a pathogenic strain, RacL.
AB  - The equine herpesvirus type-1 (EHV-1) strain Kentucky A (KyA) has a long history
      of repeated passage either in vivo in the Syrian hamster or in vitro in mouse L-M
      fibroblast tissue culture. This repeated passage in cells other than those of the
      natural host has caused genomic alterations of the KyA chromosome resulting in
      deletion of several genes or portions of open reading frames (ORFs). This report
      presents in vivo data from a mouse model of EHV-1 infection demonstrating the
      attenuated nature of EHV-1 strain KyA and that intranasal infection with KyA
      protects animals from subsequent challenge with a pathogenic strain, RacL, by
      reducing RacL viral titers in the lungs of the challenged animals. Mice infected
      with KyA exhibit no clinical manifestations of EHV-1 disease and do not
      experience the wasting that occurs with RacL infection. KyA-infected mice clear
      virus from the lung by day 5 post-infection (p.i.), whereas RacL infected mice
      have substantial virus titers (5 x 10(5) pfu/lung) at this time point. Intranasal
      infection with KyA followed by a challenge with RacL 4 weeks post-KyA infection
      resulted in a significant (P = 0.0079) reduction in the lung titers of the RacL
      virus. RacL was identified as the virus present in the lungs of the challenged
      mice by a PCR assay employing primers to amplify the EUS4 gene which differs in
      size by 1.2 kilobase pairs (kbp) in the two strains. Importantly, the protection
      afforded by KyA is long lasting in that challenge with RacL 15 months after KyA
      infection, results in reduced virus titers and viral clearance by day 5 post
      challenge. These results support the further consideration of EHV-1 KyA as a live
      virus vaccine.

PMID- 8864202
TI  - Characterization of Langat virus antigenic determinants defined by monoclonal
      antibodies to E, NS1 and preM and identification of a protective, non
      neutralizing preM-specific monoclonal antibody.
AB  - Hybridomas secreting monoclonal antibodies (MAb) to the tick-borne encephalitis
      (TBE) group virus, Langat virus (LGTV), were prepared. Of more than 200 MAb
      screened, 19 antibodies, which cross-reacted with the etiologic agent of Central
      European encephalitis, were selected for further characterization. Of these MAb,
      15 were specific for LGTV E glycoprotein, two for the NS1 protein, and three for
      preM protein. The two NS1-specific MAb and two of the E-specific MAb reacted with
      all six of the other TBE group viruses tested while the remainder of the E
      specific MAb failed to recognize at least one of the viruses. None of the MAb
      neutralized LGTV in cell culture assays, but one of the preM-specific MAb
      protected weanling mice against a virulent LGTV challenge. Although protective
      antibodies to E and NS1 proteins of TBE viruses were reported, our data provided
      the first evidence for protection by a non-neutralizing antibody to the preM or M
      protein of any of the tick-borne flaviviruses.

PMID- 8864203
TI  - Genetic variability of classical swine fever virus.
AB  - The genetic variability of classical swine fever virus was studied by comparative
      nucleotide sequence analysis of 76 virus isolates, collected during a half
      century from three continents. Parts of the E2 (gp55) and the polymerase gene
      coding regions of the viral genome were amplified by RT-PCR and DNA fragments of
      254 and 207 bp, respectively, were sequenced. The comparative sequence analysis
      of the E2 region revealed two main phylogenetic groups of CSFV, indicating that
      the virus apparently evolved from two ancestor nodes. Group I (represented by
      Brescia strain) consisted of old and recent American and Asian viruses, as well
      as old English isolates from the 1950s. This group was subdivided into three
      subgroups, termed I.A-I.C. Group II (represented by Alfort strain) consisted of
      relatively recent isolates from Europe, together with strain Osaka, which was
      isolated in Japan from a pig of European origin. Based on genetic distances the
      group was divided into subgroups II.A and II.B. Malaysian isolates were branched
      into both groups, indicating multiple origins for contemporaneous outbreaks in
      that country. All ten vaccine strains tested were branched in group I, implying a
      common ancestor. The Japanese Kanagawa strain, isolated in 1974, and the British
      Congenital Tremor strain from 1964 were the most distinct variants of CSFV in our
      collection. The comparison of the nucleotide sequences of the polymerase coding
      region of 32 European strains distinguished subgroups II.A and II.B which were
      similar to the corresponding subgroups of the E2 phylogenetic tree. Thus, the
      results revealed that the E2 region and the polymerase coding regions seem to be
      appropriate for the grouping of CSFV isolates from all over the world,
      distinguishing two major groups of the virus. The reliability of these regions
      for phylogenetic analysis is indicated by the similarity of the results obtained
      from the two separate parts of the CSFV genome.

PMID- 8864204
TI  - Geographic distribution and epidemiology of peste des petits ruminants virus.
AB  - Peste des petits ruminants (PPR) is an important viral disease of goats and sheep
      prevalent in West Africa and the Middle East. In recent years, PPR has emerged in
      India, first in the South India and later in North India. To study the genetic
      relationships between viruses of distinct geographical origin we have sequenced a
      322 nucleotide cDNA fragment of the fusion protein gene generated using reverse
      transcription followed by polymerase chain reaction (PCR) amplification. Viruses
      from nineteen independent PPR outbreaks were compared; these included the
      prototype African strain from Senegal and viruses from disease outbreaks which
      have occurred at different times and locations across Africa, Arabia, the Near
      East and the Indian subcontinent. Four separate lineages of the virus were
      identified and the virus isolates from Asia over the past 2 years were all of one
      lineage which had not previously been identified in Africa or Asia.

PMID- 8864205
TI  - Expression and characterisation of the NS1 and NS2 proteins of respiratory
      syncytial virus.
AB  - The NS1 and NS2 proteins of human respiratory syncytial virus (RSV) were
      expressed using baculovirus. Antisera to these expressed proteins and to
      synthetic peptides were raised in rabbits and used to characterise the proteins.
      Multiple forms of both NS1 and NS2 proteins were detected in RSV infected cells
      by both immunoblotting and radioimmunoprecipitation when non-reducing, but not
      reducing, conditions were used. In pulse-labelling experiments the monomeric form
      of NS1 was stable, while that of NS2 was unstable with a half life of about 30
      min. The NS1 protein associated with the matrix (M) protein and could be co
      precipitated by a monoclonal antibody to M protein. The NS2 protein did not show
      any detectable association with RSV structural proteins. These results indicate
      that the NS1 and NS2 proteins have distinct roles in the viral life cycle.

PMID- 8864206
TI  - Expression of the major inner capsid protein of the epizootic haemorrhagic
      disease virus in baculovirus and potential diagnostic use.
AB  - The RNA 7 encoding the major capsid protein (VP7) of epizootic haemorrhagic
      disease virus (EHDV), Australian serotype 2 (strain CS439), was cloned and the
      complete nucleotide sequence was determined. The coding region contained 1047
      nucleotides (nt) capable of encoding a predicted 349 amino acid (aa) polypeptide
      with a calculated molecular size of 38.087 kDa. When the VP7 gene was expressed
      in bacterial or yeast expression systems, the expression product showed weak or
      no reactivity with polyclonal antibodies to EHDV. Therefore, the expression of
      the VP7 gene in baculovirus was pursued. The expressed EHDV VP7 was similar in
      antigenicity to that of the native virus as revealed by its reactivity in ELISA
      with monoclonal antibody (MAb) specific to EHDV. Preliminary ELISA results
      indicated that the recombinant protein binds to EHDV antibodies in serum and that
      these antibodies block the binding of EHDV-specific MAb. The availability of a
      reliable EHDV recombinant VP7 could enhance our existing assay for detection of
      EHDV-specific antibodies.

PMID- 8864207
TI  - Experimental evaluation of a modular approach to mobilizing antitobacco
      influences of peers and parents.
AB  - The experimental evaluation of two components of a community intervention to
      prevent adolescent tobacco use are described. Youth antitobacco activities (e.g.,
      peer quizzes, sidewalk art, poster and T-shirt giveaways, etc.) and family
      communications activities (pamphlets to parents and student quizzes of parents)
      were evaluated in two time-series experiments, each of which was conducted in two
      experimental and one control community. Students in Grades 6 and 8 and their
      parents were assessed in a series of four phone surveys in the first experiment
      and six phone surveys in the second. Implementation of the youth antitobacco and
      family communications activities led to significantly greater exposure of young
      people to antitobacco information. They led to increases in parent and youth
      knowledge about tobacco use and more negative attitudes toward tobacco. In
      Experiment 2, youths in intervention communities had significantly lower rated
      intentions to smoke. The findings suggest the value of a modular approach to
      community interventions for influencing the social context relevant to the onset
      of adolescent tobacco use.

PMID- 8864208
TI  - The long-term outcome of a personal network-oriented HIV prevention intervention
      for injection drug users: the SAFE Study.
AB  - Social influence processes have been found to affect numerous drug and health
      related behaviors. We postulated that by using a network-oriented intervention it
      may be possible to capitalize on social influence processes to reduce human
      immunodeficiency virus (HIV) risk behaviors. The present study used an
      experimental study design for delivering a psychoeducational acquired
      immunodeficiency syndrome (AIDS) preventive intervention to injection drug
      sharing networks. Participants were recruited from the ALIVE study, an
      epidemiological study in Baltimore. In the present paper we examine the self
      reported behavioral outcomes of 117 injection drug users 18 months after the
      baseline interview. HIV seronegative experimental participants reported
      significantly less frequent needle sharing and less injecting of heroin and
      cocaine than controls. In multiple logistic regression models of HIV seronegative
      participants, there was a significant negative association between assignment to
      the experimental group and the HIV-related behaviors of needle sharing and
      sharing of cookers in the prior 6 months; controls were 2.8 times more likely
      than experimentals to report needle sharing and were 2.7 times more likely to
      report sharing cookers. The results of this 18-month follow-up suggest that among
      injection drug users network-oriented interventions may be a promising approach
      to HIV prevention.

PMID- 8864209
TI  - Family, peer, and neighborhood influences on academic achievement among African
      American adolescents: one-year prospective effects.
AB  - Using a 1-year prospective design, this study examined the influence of family
      status variables (family income, parental education, family structure), parenting
      variables (maternal support and restrictive control), peer support, and
      neighborhood risk on the school performance of 120 African American junior high
      school students. In addition to main effects of these variables, neighborhood
      risk was examined as a moderator of the effects of parenting and peer support.
      Family status variables were not predictive of adolescent school performance as
      indexed by self-reported grade point average. Maternal support at Time 1 was
      prospectively related to adolescent grades at Time 2. Neighborhood risk was
      related to lower grades, while peer support predicted better grades in the
      prospective analyses. Neighborhood risk also moderated the effects of maternal
      restrictive control and peer support on adolescent grades in prospective
      analyses. These findings highlight the importance of an ecological approach to
      the problem of academic underachievement within the African American Community.

PMID- 8864210
TI  - Evidences for a stage-specific juvenile hormone binding protein in the hemolymph
      of the silkworm, Bombyx mori L.: identification and characterization by
      photoaffinity labeling and immunological analyses.
AB  - Two molecular forms of juvenile hormone binding proteins were identified in the
      larval hemolymph of Bombyx mori by photoaffinity labeling. One form having an Mr
      of 33 kDa was present constantly in the hemolymph of the third to the fifth
      instar larvae while the other form having an Mr of 35 kDa was detected in the
      hemolymph until in the early fifth instar larvae but not in the prewandering
      larvae and prepupae. A 33 kDa binding protein was purified by hydrophobic
      interaction chromatography, gel filtration, and native PAGE. Antiserum against 33
      kDa binding protein cross-reacted with 35 kDa binding protein on Western blots,
      suggesting that these binding proteins shared the same epitopes. From the results
      of saturation binding assays, it was inferred that 33 and 35 kDa binding proteins
      had a similar binding affinity for JH I. It was revealed that one of these
      binding proteins, 35 kDa binding protein, was produced in the fat body in a stage
      specific manner: fat body of the early fifth instar larvae synthesized both 33
      and 35 kDa binding proteins while that of prewandering larvae synthesized only 33
      kDa binding protein.

PMID- 8864211
TI  - Methionine-rich hexamerin and arylphorin as precursor reservoirs for reproduction
      and metamorphosis in female luna moths.
AB  - The storage proteins of Lepidoptera include a pair of methionine-rich hexamerins
      (MtH) that are more abundant in female pupae than in males. Their inferred
      support of female reproduction could be achieved either by enhancing general
      pools of amino acids, or by hydrolyzing MtH at times and/or sites that direct its
      constituents to the synthesis of egg proteins. The two models were tested in
      Actias luna, a saturniid moth that makes its eggs during adult development. MtH
      and arylphorin (ArH), the third major storage protein of this species, were
      labeled metabolically with [35S]-methionine and [3H]-leucine, and injected
      individually into wandering stage caterpillars. Isotope distributions at eclosion
      indicated that both hexamerins supported egg formation as well as adult tissue
      protein synthesis. In the absence of evidence for targeting, MtH appears to
      support egg formation in A. luna by enhancing the amino acid pools derived from
      ArH. Analysis of 35S labeling and of 35S/3H ratios indicated, however, that ArH
      is consumed over a period that extends somewhat later in adult development than
      MtH. Differences in timing should prove to be much greater in Lepidoptera that
      delay egg formation until after eclosion.

PMID- 8864212
TI  - Development of techniques for the genetic manipulation of the gliding bacteria
      Lysobacter enzymogenes and Lysobacter brunescens.
AB  - Lysobacter enzymogenes and Lysobacter brunescens are Gram-negative gliding
      bacteria that belong to the gamma subgroup of the proteobacteria. As a first step
      toward a molecular analysis of Lysobacter gliding motility, we developed
      techniques to genetically manipulate these bacteria. Cosmid pSUP106 of the broad
      host range incompatibility group Q (Inc Q) was introduced into L. enzymogenes and
      L. brunescens by conjugation and electroporation. pSUP106 replicated stably in
      both organisms and conferred antibiotic resistance. We also identified several
      other plasmids (pKT210, pH1JI) that functioned in L. enzymogenes and a transposon
      (mini-Tn5Sp) that functioned in L. brunescens. The identification of these tools
      allows genetic analysis of Lysobacter gliding motility, exoenzyme production, and
      production of antibiotics and other secondary metabolites.

PMID- 8864213
TI  - A 150-megadalton plasmid in Rhizobium etli strain TAL182 contains genes for
      nodulation competitiveness on Phaseolus vulgaris L.
AB  - Rhizobium etli TAL182, a competitive strain for the nodulation of Phaseolus
      beans, occupied more than 99% of the nodules when co-inoculated in various
      proportions with Rhizobium TAL1145 or Rhizobium tropici CIAT899. Two overlapping
      cosmid clones, pUHR68 and pUHR69, containing genes for nodulation competitiveness
      from TAL182, were isolated by functional complementation of strain TAL1145. Using
      one of these cosmid clones, we constructed two Tn5-insertion mutants of TAL182
      defective in nodulation competitiveness. The Tn5 insertions in both mutants were
      localized in identical positions within a 4.6-kb HindIII fragment. One mutant,
      RUH120, was complemented for nodulation competitiveness by this HindIII fragment.
      The cloned DNA in pUHR68 is a part of a plasmid, 150 MDa in size, in TAL182 and
      does not show homology with TAL1145 genomic DNA. The 4.6-kb HindIII fragment
      contains a gene(s) required for nodulation competitiveness on beans, which is
      present only in some R. etli strains and absent in other Rhizobium spp.

PMID- 8864214
TI  - Cloning and characterization of transcriptional promoters from Bacillus subtilis
      phage 2C.
AB  - Phage 2C is a Bacillus subtilis lytic phage, whose genome contains
      hydroxymethyluracil in place of thymine. To isolate promoters of early phage
      genes involved in the take-over of cellular metabolism, 2C DNA libraries were
      constructed in promoter-probe plasmids replicating in Escherichia coli and B.
      subtilis. Four different 2C DNA fragments strongly expressed reporter genes in E.
      coli but not in B. subtilis. All fragments originated from unique sequences of
      the genome and not from its terminal redundancies. One fragment was sequenced.
      Despite the presence of an sigma-A-RNA polymerase binding site upstream of the
      transcriptional initiation site of a 2C early gene, this fragment did not promote
      transcription in B. subtilis.

PMID- 8864215
TI  - Effects of a strain of Saccharomyces cerevisiae (Levucell SC1), a microbial
      additive for ruminants, on lactate metabolism in vitro.
AB  - The effect of Levucell SC, a strain of Saccharomyces cerevisiae marked as a feed
      additive for ruminants, was investigated in vitro on lactate metabolism by the
      ruminal bacteria Streptococcus bovis and Megasphaera elsdenii. The coculture
      between 10(7) live cells x mL(-1) of SC and a Streptococcus bovis strain in the
      presence of glucose reduced lactate production by the bacterial strain. Live
      yeast cells were able to compete with Streptococcus bovis for glucose utilization
      in strictly anaerobic conditions, so less glucose was available for the
      bacterium. SC also stimulated L-lactate utilization by a strain of M. elsdenii.
      The effect depended on the concentration of yeast cells added. Bacterial growth
      and fermentation end-product concentrations were also increased in the presence
      of SC. Some amino acids and vitamins, but not dicarboxylic acids, stimulated the
      bacterial specific activity of L-lactate uptake. SC was able to provide amino
      acids to M. elsdenii. In a coculture of Streptococcus bovis and M. elsdenii on
      glucose, the reduction of lactate concentration was improved by SC, the same
      trend being observed when maltose or soluble starch were used as carbon and
      energy source. These results indicate that SC can be a very useful tool to reduce
      lactate accumulation in vitro during fermentation of soluble sugars.

PMID- 8864216
TI  - Endoglucanase G from Fibrobacter succinogenes S85 belongs to a class of enzymes
      characterized by a basic C-terminal domain.
AB  - A 3.6-kb fragment of the Fibrobacter succinogenes S85 DNA was sequenced and found
      to contain two open reading frames (ORFs) on the same strand separated by 242
      nucleotide bases. The translated protein from ORF1 had a predicted mass of 52.3
      kDa. In a region of 320 amino acid overlap, it shares a 35% identity with the b
      chain of the glutamate synthase of Escherichia coli. The ORF2 protein encodes a
      519 residue protein designated CelG. It consists of an ORF of 1557 bp, encoding a
      polypeptide of 54.5 kDa. The N-terminal region, which contains the catalytic
      domain, is linked to a C-terminal basic domain, which has a predicted isoelectric
      point of 10.8. The catalytic domain in endoglucanase G (CelG) is homologous to
      the family 5 (A) cellulases. The enzyme has an apparent mass of 55 kDa, a pH
      optimum of 5.5, and temperature optimum of 25 degrees C. It had a specific
      activity of 16.5 mumols x min(-1) x mg-1 on barley b-glucan and produced a
      mixture of cellooligosaccharides from the hydrolysis of acid swollen cellulose
      and cellooligosaccharides. Antiserum raised against the purified form of CelG in
      E. coli failed to react with proteins from the native organism when grown on
      either glucose or crystalline cellulose, but reverse transcription and polymerase
      chain reaction techniques using RNA from the native organism demonstrated that
      the celG gene was expressed constitutively. Its distribution amongst subspecies
      of Fibrobacter was restricted to F. succinogenes S85.

PMID- 8864217
TI  - Leishmania (V.) guyanensis: isolation and characterization of glucantime
      resistant cell lines.
AB  - A glucantime sensitive Leishmania (V.) guyanensis strain was used to obtain in
      vitro resistant cell lines, by increments in glucantime concentrations employing
      both one step and stepwise protocols. Whereas the effective concentration of drug
      that inhibited the growth of wild type cells by 50% (EC50 value) was 0.20 mg
      Sb(v)/mL, the resistant cells were able to grow in glucantime concentrations
      greater than 8.0 mg/mL. The resistant cell lines were partially characterized by
      their in vitro response to glucantime, the stability of resistance phenotype,
      cross resistance to a range of drugs, and also by the analysis of total DNA
      fragments generated by restriction endonucleases and blot hybridization.
      Amplified DNA sequence similar to a P-glycoprotein analog from Leishmania
      tarentolae (ltpgpA gene) was observed in all the resistant cell lines obtained
      through the one-step protocol. These cell lines showed cross resistance to heavy
      metals but were sensitive to puromycin, vinblastine, and pentostam.

PMID- 8864219
TI  - A comparative study of the broth micro- and macro-dilution techniques for the
      determination of the in vitro susceptibility of Aspergillus fumigatus.
AB  - The effects of inoculum size, medium, temperature, and duration of growth on the
      in vitro susceptibility testing of Aspergillus fumigatus were investigated using
      broth micro- and macro-dilution techniques. The minimum inhibitory concentrations
      (MICs) of ketoconazole, miconazole, itraconazole, fluconazole, and amphotericin B
      were significantly influenced by the inoculum size, regardless of the techniques
      used. Two- to four-fold higher MIC values were obtained when the inoculum size
      was increased 100-fold. The use of peptone yeast extract glucose and RPMI 1640
      media provided essentially identical MIC values at 30 and 35 degrees C after
      incubation for 48 h or longer. A comparison of broth micro- and macro-dilution
      techniques revealed that, under equivalent conditions, the latter with an
      inoculum size between 1 x 10(3) and 1 x 10(4) conidia (strain W73355)/mL
      consistently provided the lowest MICs of fluconazole (256 micrograms/mL),
      ketoconazole (8 micrograms/mL), miconazole (2 micrograms/mL), itraconazole (0.25
      micrograms/mL), and amphotericin B (0.25 micrograms/mL). Using the broth
      macrodilution technique we screened 24 clinical isolates of A. fumigatus obtained
      from the Detroit Medical Center in 1994. The MIC values of fluconazole,
      ketoconazole, miconazole, itraconazole and amphotericin B for all the isolates
      were 128-256, 8-16, 1-2, 0.25-0.5, and 0.25-1.0 micrograms/mL, respectively,
      indicating that none of the clinical isolates that we tested shows acquired
      resistance to the antifungals used.

PMID- 8864218
TI  - Analysis of mutations in the creA gene involved in carbon catabolite repression
      in Aspergillus nidulans.
AB  - The molecular nature of a number of creA mutant alleles has been determined.
      Three alleles analysed are missense mutations in the DNA binding domain and
      predicted to reduce but not abolish binding. Of the other four alleles, two
      result from frameshifts: one has a nonsense mutilation and the other has an
      inversion. All four alleles result in truncations of the protein after the zinc
      finger domain, such that the protein no longer contains at least the carboxy
      terminal 145 amino acids, so identifying a region required for repression.
      Transcriptional analysis of creA indicates that the transcript is autoregulated
      and analysis using 5' rapid amplification of cDNA ends indicates that
      transcriptional start points exist in clusters over a region of 200 bp located up
      to 595 bp 5' of the translational start point. The two major clusters have
      potential CREA-binding sites (SYGGRG) at appropriate positions to allow
      autoregulation. Autoregulation leads to the creA transcript being most abundant
      in carbon catabolite nonrepressing conditions, and this, together with the
      phenotypes of the mutant alleles, has led to the suggestion that CREA has effects
      under conditions generally not considered as carbon catabolite repressing, as
      well as in carbon catabolite repressing conditions.

PMID- 8864220
TI  - Investigation of the conformational behaviour of permethylated cyclodextrins by
      molecular modelling.
AB  - Conformations of manually built native and permethylated alpha-, beta-, and gamma
      cyclodextrins (CD) were investigated using various computer assisted molecular
      modelling methods. Calculations were carried by applying the MM+ and the Tripos
      force field. The influences of atomic charges on the macrocyclic conformations
      during the optimization procedure were analyzed. The permethylation of hydroxyl
      groups of cyclodextrins changes bond and torsion angles between the glucose
      monomers and of the primary substituents. A method to determine the diameters of
      the cyclodextrin cavity by a modelling approach is described. It is shown that
      due to permethylation the larger cavity opening is increased and the primary
      substituents are canted outwards. As a consequence, the torus shape of the
      molecule changes, which is an important feature for docking and fitting studies.

PMID- 8864221
TI  - Efficient, convergent syntheses of oligosaccharide allyl glycosides corresponding
      to the Streptococcus group A cell-wall polysaccharide.
AB  - Convergent syntheses of di-, tri, tetra-, penta-, and hexa-saccharide allyl
      glycosides corresponding to the beta-hemolytic Streptococcus Group A cell-wall
      polysaccharide are described. The strategy relies on the preparation of related
      di- and tri-saccharide building blocks: beta-D-Glc pNAc-(1-3)-alpha-L-Rhap and
      alpha-L-Rhap-(1-2)-[(beta-D-Glc p NAc-(1-3)]-alpha-L-Rhap, which could be used
      either as glycosyl donors or acceptors in subsequent glycosylation reactions. The
      protecting groups were chosen to allow the selective removal of the allyl aglycon
      to access the intermediate glycosyl donors but also to allow their own removal
      without affecting the allyl group. The allyl group was intended for use in
      conjugation of the oligosaccharides to soluble protein carriers or solid supports
      for the preparation of antigens and immunoadsorbents, respectively.

PMID- 8864222
TI  - Evaluation of C-(beta-D-galactosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) (D
      galactal type) derivatives as inhibitors of beta-D-galactosidase from Escherichia
      coli.
AB  - C-(2-Deoxy-D-lyxo-hex-1-enopyranosyl)formamide was prepared from acetylated C
      (beta-D-galactopyranosyl)formamide by a radical-mediated bromination-zinc/N
      methylimidazole-induced reductive elimination-Zemplen deacetylation reaction
      sequence. The preparation of acetylated 5-(2-deoxy-D-lyxo-hex-1
      enopyranosyl)tetrazole was improved. Methyl C-(2-deoxy-D-lyxo-hex-1
      enopyranosyl)formimidate was transformed by benzylamine into N-benzyl-C-(2-deoxy
      D-lyxo-hex-1-enopyranosyl)formamidine and, after hydrolysis to methyl C-(2-deoxy
      D-lyxo-hex-1-enopyranosyl)formate, into N-benzyl-C-(2-deoxy-D-lyxo-hex-1
      enopyranosyl)formamide. A series of C-(beta-D-galactopyranosyl) and C-(2-deoxy-D
      lyxo-hex-1-enopyranosyl) derivatives was comparatively investigated for E. coli
      beta-D-galactosidase inhibitory activity. N-Benzyl-C-(2-deoxy-D-lyxo-hex-1
      enopyranosyl)formamidine was the best inhibitor and had K(i) = 6 microM (on the
      basis of its free base concentration, K(i) = 8.3 nM was obtained). Basicity and
      hydrophobicity of the aglycon proved to be more important factors for the
      inhibition than the conformation of the sugar ring.

PMID- 8864223
TI  - Interglycosidic acetals. Part 3. Synthesis and structure determination of cyclic
      monobenzylidene acetals of cyclodextrin derivatives bridging between two
      contiguous D-glucopyranosyl residues.
AB  - Transacetalation of fully 6-O-pivaloylated alpha-, beta-, and gamma-cyclodextrins
      with benzaldehyde dimethylacetal in the presence of (+)-10-camphorsulfonic acid
      gave monobenzylidene acetals (4, 5, 6) in moderately good yields. Benzylation of
      the beta-cyclodextrin derivative 5 followed by acid-catalyzed hydrolysis of the
      benzylidene group and acetylation afforded a di-O-acetyl-non-adeca-O-benzyl
      derivative 9. NMR spectroscopic analysis of 9, including two-dimensional HOHAHA
      and 1H-(13)C correlation experiments revealed that the benzylidene group bridged
      the O-2 and O-3 positions of contiguous D-glucopyranosyl residues. Reductive ring
      opening of the benzylidene acetal with lithium aluminum hydride/aluminum chloride
      afforded predominantly a 2(1)-O-unprotected derivative 10 in good yield.

PMID- 8864224
TI  - Synthesis of Hex p-(1-->4)-beta-D-Glc pNAc-(1-->2)-alpha-D-Man p-(1-->O)(CH2)7CH3
      probes for exploration of the substrate specificity of glycosyltransferases: Part
      I, Hex = beta-D-Gal, 4-deoxy-beta-D-Gal, 4-O-methyl-beta-D-Gal, 4-deoxy-4-fluoro
      beta-D-Gal, or beta-D-Glc.
AB  - Five trisaccharide derivatives designed for detailed exploration of the acceptor
      specificity of glycosyltransferases involved in termination of N
      acetyllactosamine-type structures have been synthesized: beta-D-Gal p-(1-->4)
      beta-D-Glc pNAc-(1-->2)-alpha-D-Man p-(1-->0)(CH2)7CH3 (1), 4-deoxy-beta-D-Gal p
      (1-->4)-beta-D-Glc pNAc-(1-->2)-alpha-D-Man p-(1-->O)(CH2)7CH3 (2), 4-O-methyl
      beta-D-Gal p-(1-->4)-beta-D-Glc pNAc-(1-->2)-alpha-D-Man p-(1-->O)(CH2)7CH3 (3),
      4-deoxy-4-fluoro-beta-D-Gal p-(1-->4)-beta-D-Glc pNAc-(1-->2)-alpha-D-Man p(1-
      >O)(CH2)7CH3 (4), and beta-D-Glc p-(1-->4)-beta-D-Glc pNAc-(1-->2)-alpha-D-Man p
      (1-->O)(CH2)7CH3 (5). A general disaccharide acceptor octyl 3,4,6-tri-O-benzyl-2
      O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D -glucopyranosyl)-alpha-D
      mannopyranoside was synthesized by condensation of 4-O-acetyl-3,6-di-O-benzyl-2
      deoxy-2-phthalimido-alpha, beta-D-glucopyranosyl trichloroacetimidate with octyl
      3,4,6-tri-O-benzyl-alpha-D-mannopyranoside, followed by deacetylation. 2,3,4,6
      Tetra-O-acetyl-alpha-D-galactopyranosyl trichloroacetimidate and 2,3,4,6-tetra-O
      acetyl-alpha-D-glucopyranosyl trichloroacetimidate were used as the glycosyl
      donors in the syntheses of 1 and 5. The modified galactosyl derivatives required
      subtle anomeric activation. Suitable donors for 2 turned out to be 2,3,6-tri-O
      acetyl-4-deoxy-alpha-D-xylo-hexopyranosyl trichloroacetimidate and ethyl 2,3,6
      tri-O-acetyl-4-deoxy-1-thio-alpha, beta-D-xylo-hexopyranoside; for 3, ethyl 2,3,6
      tri-O-acetyl-4-O-methyl-1-thio-alpha, beta-D-galactopyranoside; and for 4, 2,3,6
      tri-O-acetyl-4-deoxy-4-fluoro-alpha-D-galactopyranosyl trichloroacetimidate. It
      was concluded that thioglycosides were most appropriate for stereoselective
      coupling of activated synthons (carrying deoxy or O-methyl groups), whereas
      trichloroacetimidates gave high yields with deactivated (fluorine-containing)
      synthons.

PMID- 8864225
TI  - Selective cleavage of welan gum (S-130) by oxidative decarboxylation with lead
      tetraacetate.
AB  - Oxidative decarboxylation of peracetylated welan gum (S-130) with lead
      tetraacetate resulted in selective cleavage of the glucuronosidic linkages.
      Products of the degradation were reduced with sodium borohydride, O-deacetylated,
      and fractionated. Polymeric and oligomeric fractions were separated and analysed
      by 1H NMR spectroscopy and fast atom bombardment mass spectrometry, and were
      found to be monomers, dimers, and trimers of the repeating unit. Results show
      that this method may be used to liberate alditol-terminated multiples of the
      repeating unit of peracetylated glycuronans by cleavage and degradation of the
      uronic acid residues. The reaction sequence also confirms the recent finding that
      welan gum contains repeating units with randomly distributed terminal groups.

PMID- 8864226
TI  - HPLC analysis of saturated or unsaturated oligoguluronates and oligomannuronates.
      Application to the determination of the action pattern of Haliotis tuberculata
      alginate lyase.
AB  - The chromatographic behaviour of various saturated and unsaturated oligouronates
      obtained by acid or enzymatic degradation of homopolymeric blocks of alginates
      was investigated by isocratic anion exchange liquid chromatography. This approach
      was then applied to the determination of the catalytic properties of Haliotis
      tuberculata alginate lyase. This enzyme presents a high affinity for poly-beta-D
      mannuronate blocks, leading to the release of O-(4-deoxy-alpha-L-erythro-hex-4
      enopyranosyluronic acid)-(1-->4)-O-(beta-D-mannopyranosyluronic acid)-(1-->4)-O
      beta-D-mannopyranuronic acid as the main end reaction product. Kinetic analysis
      with oligomannuronates of various sizes indicate that the catalytic site of
      Haliotis tuberculata lyase (abalone) best accommodates an oligomannuronate
      pentamer. The abalone lyase, however, is also capable of cleaving the G-M
      linkages of alginate heteropolymeric sequences. In contrast, it does not degrade
      the G-G nor the M-G diads. This lyase should therefore be referred to as a
      mannuronate beta-eliminase, indicating that the enzyme performs beta-elimination
      on mannuronate residues only, from both the M-M and G-M diads of alginates.

PMID- 8864227
TI  - Structural studies of the enteroinvasive Escherichia coli (EIEC) O28 O-antigenic
      polysaccharide.
AB  - The structure of the O-specific side-chain of the lipopolysaccharide from
      Escherichia coli O28 has been investigated. NMR spectroscopy has been the main
      method used, complemented with sugar and methylation analyses. The polysaccharide
      contains one equivalent of O-acetyl groups per repeating unit. Selective cleavage
      of the O-deacetylated polymer was performed by treatment with aqueous
      hydrofluoric acid, and resulted in a trisaccharide-glycerol. The polysaccharide
      thus is of the teichoic acid type and composed of repeating units in which the
      trisaccharide-glycerol residues are joined by phosphodiester linkages. The O
      antigen polysaccharide has the following structure. [sequence: see text] The
      absolute configuration of the glycerol moiety as R, )i.e., D-glycerol 1
      phosphate) was determined by a new method based on TEMPO oxidation of the
      polysaccharide, followed by GLC analysis of the (+)-2-butyl ester of the
      resulting glyceric acid.

PMID- 8864228
TI  - Structural elucidation of an extracellular polysaccharide produced by
      Lactobacillus helveticus.
AB  - An extracellular polysaccharide produced by a strain of Lactobacillus helveticus
      isolated from cheese milk has been investigated. Sugar and methylation analysis
      together with 1H and 13C NMR spectroscopy revealed that the polysaccharide is
      composed of hexasaccharide repeating units. The sequence of sugar residues was
      determined by use of two-dimensional nuclear Overhauser effect spectroscopy and
      heteronuclear multiple-bond correlation experiments. The structure of the
      repeating unit of the exopolysaccharide from L. helveticus is as follows:
      [sequence: see text]

PMID- 8864229
TI  - Structural studies of the O-antigenic polysaccharide from an Aeromonas caviae
      strain.
AB  - The structure of the O-antigenic polysaccharide from a strain of Aeromonas
      caviae, isolated from the stools of a patient with diarrhoea, has been
      investigated. Sugar analysis, methylation analyses, and a uronic acid degradation
      together with NMR spectroscopy were the principal methods used. The sequence of
      the sugar residues could be determined by NOESY and HMBC experiments. It is
      concluded that the polysaccharide is composed of pentasaccharide repeating units
      with the following structure: [sequence: see text]

PMID- 8864231
TI  - An efficient synthesis of 3,4,6-tri-O-benzyl-2-C-methyl-D-glucal.

PMID- 8864232
TI  - Structure determination of the O-antigen polysaccharide from the enteroinvasive
      Escherichia coli (EIEC) O143 by component analysis and NMR spectroscopy.

PMID- 8864233
TI  - Somatic antigens of pseudomonads: structure of the O-specific polysaccharide of
      the reference strain for Pseudomonas fluorescens (IMV 4125, ATCC 13525, biovar
      A).

PMID- 8864234
TI  - Copper in biological systems. A report from the 7th Manziana Conference, held at
      Santa Severa, September 11-15, 1995.
AB  - In this fifty-seven page report, the author attempts to give the essence of the
      twenty-four lectures and of an about equal number of posters, including subjects
      of discussion, that were presented at an international conference on copper
      proteins held in Italy. The report deals with research carried out up to mid-1995
      and contains 140 literature references and thirty-three figures or schemes.

PMID- 8864235
TI  - Macrocarpals H, I, and J from the Leaves of Eucalyptus globulus.
AB  - A 50% EtOH extract of Eucalyptus globulus leaves yielded eight phloroglucinol-
      sesquiterpene-coupled constituents, including three novel compounds named
      macrocarpals, H, I, and J. Some of these compounds possessed antibacterial
      activity against oral pathogenic microorganisms with MIC values ranging from 0.20
      micrograms/mL to 6.25 micrograms/mL. Inhibition of glucosyltransferase activity
      by these compounds was also noted.

PMID- 8864236
TI  - Novel antiplatelet constituents from formosan moraceous plants.
AB  - Sixteen constituents from Formosan Moraceous plants were tested for their
      antiplatelet activities in rabbit platelet suspension and human platelet-rich
      plasma. Cycloartocarpin A, cycloheterophyllin, broussochalcone A, kazinol A,
      broussoaurone A, and broussoflavonol F showed strong inhibition of arachidonic
      acid (AA)-induced platelet aggregation. Of the compounds tested, broussochalcone
      A exhibited the most potent inhibition of platelet aggregation induced by AA
      (IC50 = 6.8 microM). The antiplatelet effects of cycloheterophyllin,
      broussochalcone A, kazinol B, broussoaurone A, and broussoflavonol F are
      partially due to an inhibitory effect on cyclooxygenase.

PMID- 8864237
TI  - Specific inhibition of human immunodeficiency virus type 1 reverse transcriptase
      mediated by soulattrolide, a coumarin isolated from the latex of calophyllum
      teysmannii.
AB  - Soulattrolide (1), a coumarin isolated from Calophyllum teysmannii latex, was
      found to be a potent inhibitor of HIV-1 reverse transcriptase (RT) with an IC50
      of 0.34 microM. Inhibition was remarkably specific, with no appreciable activity
      being observed toward HIV-2 RT, AMV RT, RNA polymerase, or DNA polymerases alpha
      or beta.

PMID- 8864238
TI  - New macrocyclic spermine (budmunchiamine) alkaloids from Albizia gummifera: with
      some observations on the structure--activity relationships of the
      budmunchiamines.
AB  - The CH2Cl2 extract of the stem bark of Albizia gummifera yielded four macrocyclic
      spermine alkaloids (budmunchiamines), three of them being new analogues. On the
      basis of spectral analysis and comparison with related compounds they were
      identified as budmunchiamine G (1) and the new analogues budmunchiamine K (2),
      6'xi-hydroxybudmunchiamine K (3), and 9-normethylbudmunchiamine K (4). The four
      isolated alkaloids and other related budmunchiamines isolated from Albizia
      schimperana were all active against two Gram-positive and two Gram-negative
      bacteria at MIC levels below 80 micrograms mL(-1), and showed toxicity to brine
      shrimp larvae (with LC50 values below 100 micrograms mL(-1)). The negative impact
      of side chain hydroxylation and N-demethylation on both measures of biological
      activity was shown to be considerable.

PMID- 8864239
TI  - Three new naphthyldihydroisoquinoline alkaloids from Ancistrocladus tectorius.
AB  - Three new 5--1'-linked naphthyldihydroisoquinoline alkaloids (1-3) have been
      isolated from the organic extract of Ancistrocladus tectorius. The gross
      structures of the compounds have been established using 1D and 2D NMR
      spectroscopy and difference NOE experiments. The absolute stereochemistry of 1,
      2, and 3 was determined from CD spectral comparison and chemical degradation.
      Evidence is presented to show that two of the compounds exist exclusively in the
      keto form at C-8 of the isoquinoline system (2b, 3b).

PMID- 8864240
TI  - A new secotrinervitane diterpene isolated from soldiers of the Madagascan termite
      species, Nasutitermes canaliculatus.
AB  - Reported herein is the X-ray crystallographic structure of a novel 10-oxygenated
      secotrinervitane diterpene, 3 alpha, 10 alpha-diacetoxy-7,16-secotrinervita
      7,11,15(17)-triene (4), from soldiers of the endemic Madagascan termite
      Nasutitermes canaliculatus, which was compared with an energy-minimized structure
      obtained by computer molecular modeling. We also report 1H- and 13C-NMR and MS
      data for this new diterpene.

PMID- 8864241
TI  - Antiviral sulfated steroids from the ophiuroid Ophioplocus januarii.
AB  - One new and three known sulfated steroidal polyols have been isolated from the
      ophiuroid Ophioplocus januarii, collected at San Antonio Oeste, Rio Negro,
      Argentina. The four compounds possess 4 alpha,11 beta-dihydroxy-3 alpha,21
      disulfoxy substituents and the A/B cis ring junction but differ in the side
      chain. The new compound has been characterized as (22E)-5 beta-24-norcholest-22
      ene-3 alpha,4 alpha,11 beta,21-tetrol 3,21-disulfate (4). The structures of the
      four compounds were determined from spectral data and comparison with those of
      related steroidal polyols. The four compounds were tested for their inhibitory
      effect on the replication of one DNA and three RNA viruses. Compounds 2 and 4
      were active against respiratory syncytial and polio viruses, and compound 3
      inhibited Junin virus, responsible for Argentine hemorrhagic fever.

PMID- 8864242
TI  - (Hydroxymethyl)acylfulvene: an illudin derivative with superior antitumor
      properties.
AB  - Reaction of the fungal sesquiterpene illudin S with excess paraformaldehyde in
      dilute H2SO4 gives (hydroxymethyl)acylfulvene. The primary allylic hydroxyl thus
      formed can undergo very facile replacement by a variety of nucleophiles.
      (Hydroxymethyl)acylfulvene (MGI.114) was more toxic than a precursor,
      acylfulvene, but less toxic than the parent compound illudin S to HL 60 cells.

PMID- 8864243
TI  - Diterpenoid alkaloids from Consolida oliveriana.
AB  - From the aerial parts of Consolida oliveriana (DC) Schrod. a new norditerpenoid
      alkaloid consolidine (2) has been isolated, in addition to the known alkaloids
      pubescenine (1), gigactonine, and delsoline and the diterpenoid alkaloid
      ajaconine (4). The structure of alkaloid 2 was established on the basis of its
      physical and spectroscopic data including detailed NMR studies. A detailed NMR
      study on ajaconine (4) resulted in the revision of 11 13C chemical shift
      assignments.

PMID- 8864244
TI  - Uptake and localization of lead in corn (Zea mays L.) seedlings, a study by
      histochemical and electron microscopy.
AB  - A detailed microscopic analyses of the mode of lead uptake and localization in
      root, stem and leaf initials of corn seedlings grown in cultural solution is
      reported. Lead, as other minerals, was passively absorbed into the root tip
      region and transported by the active apical growth force. The entrance of lead
      was mainly from the thin epidermal cell walls at the meristematic region. Only
      limited amounts of lead entered into protoplasts, primarily during the early
      stage of cell development. However, accumulation of lead within cell walls
      increased as cells matured. Both local and long distance transport of lead were
      apoplastic. Once the vascular stele differentiated from the ground meristem, lead
      entered into the central conducting systems. Lead was also absorbed from the
      water absorbing zone but this lead mainly remained in the cortex. The Casparin
      strip was an effective barrier limiting the movement of lead. However, transport
      through passage cells was observed. The direction of lead movement was also
      mainly towards high growth rate areas as seen at meristematic root initials, the
      leaf primordia and the transaction zone at the stem apical meristem. Damaged
      plasmalemmae allowed lead to enter cells from cell walls. Lead deposition in the
      cytoplast was observed.

PMID- 8864245
TI  - Mobility of Chernobyl-derived 137Cs in a peatbog system within the catchment of
      the Pripyat River, Belarus.
AB  - The behaviour of Chernobyl-derived 137Cs in a hydrologically isolated bog system
      in the catchment of the Pripyat River, Belarus was investigated. Measurements
      were made of 137Cs activities in the solids and pore waters of the bog soils, as
      well as the variability in activity in water draining from the bog. It was found
      that the radiocaesium activity of the pore water, and hence the measured
      distribution coefficient, Kd, was dependent upon the pressure at which the water
      was removed from the soil. Measured values of Kd were of the order 10(2) l/kg at
      an extraction pressure of 0.8 MPa, approximately one order of magnitude lower
      than those measured in a similar system, Devoke Water, in the UK [1]. Results of
      comparative measurements suggested that this was a result of the different pore
      water extraction techniques used. The vertical migration of radiocaesium was
      modelled using a solution of the advection-diffusion equation. Using a mass
      balance approach, it was estimated that 137Cs was removed from the system at a
      rate of 0.3% of the catchment inventory per year, approximately 8 years after the
      Chernobyl accident. It was shown that both vertical migration and removal of
      137Cs is best modelled using a Kd based on a measurement of pore water held at
      low pressure in the soil, approximately 10(3) l/kg. 137Cs activities in soil pore
      waters and in drainage waters were very strongly related to the aqueous potassium
      concentration, and both showed concentration minima in drainage water during the
      spring. It was shown that runoff coefficients of radiocaesium from peat bogs 8
      years after the Chernobyl accident were approximately one order of magnitude
      greater than those from unsaturated soils of higher mineral content.

PMID- 8864246
TI  - Importance of monitoring family members in establishing sources and pathways of
      lead in blood.
AB  - High precision lead isotope measurements were undertaken to establish the sources
      and pathways in blood and environmental samples of five families from the Broken
      Hill lead mining community, New South Wales, Australia. The five families were
      selected from 27 families investigated to illustrate the different sources and
      pathways of lead into blood and the importance of monitoring the whole family.
      The results illustrate that although the major source of lead is from the
      orebody, paint and petrol can be significant contributors to both house dust and
      blood leads. The results also show that the sources and pathways can be from the
      father's occupation and hence monitoring of families is important, especially in
      high risk locations. In two cases, the elevated blood leads in the children did
      not derive from their current residence but from other residences in the
      community.

PMID- 8864247
TI  - A simple method for defluoridation of drinking water at village level by
      adsorption on Ando soil in Kenya.
AB  - In this paper a new and simple defluoridation method is presented using local
      Kenyan soil derived from volcanic ash (e.g. Ando soils or soils with 'andic'
      properties) as a fluoride sorbent. The ability of Kenyan Ando soil to adsorb
      fluoride was determined experimentally. These results were extended to possible
      technical application using a one dimensional solute transport model. Based on
      the results it is concluded that the use of Ando soils appears to be an
      economical and efficient method for defluoridation of drinking water on a small
      scale in rural areas of Kenya and other regions along the Rift Zone. Further
      research is warranted to evaluate its practical applications and social
      acceptance.

PMID- 8864248
TI  - Schizophrenia throughout life: sex differences in severity and profile of
      symptoms.
AB  - BACKGROUND: The impact of aging and of gender has been examined in health and
      disease, but has received limited attention in schizophrenia. A lifespan
      perspective of gender differences can contribute to an understanding of clinical
      features and their underlying neurobiological processes. METHOD: A prospective
      sample of 272 patients with schizophrenia, divided into four age groups: < 35, 35
      65, 65-80 and > 85, was assessed with standardized procedures to measure the
      composition and severity of symptoms. RESULTS: Aging was associated with
      increased severity of symptoms and gender differences were noted. Negative
      symptoms increased in severity, while some positive symptoms ameliorated with
      aging. Women were characterized by reduced negative symptoms, and this remained
      evident until the eighth decade. CONCLUSIONS: Aging and gender moderate the
      clinical features of schizophrenia in specific symptom clusters. These effects
      may give insight into neurobiological substrates of the illness.

PMID- 8864249
TI  - Inhibitory effect of cholesterol oxides on low density lipoprotein receptor gene
      expression.
AB  - The effects of the cholesterol oxides on low density lipoprotein receptor (LDLR)
      gene expression were investigated. Cultured rabbit aortic smooth muscle cells
      were incubated with 1, 2, and 5 micrograms/ml culture medium concentrations of
      pure cholesterol, 25-hydroxycholesterol (25-OH), 7-ketocholesterol (7-keto),
      cholestane-3 beta, 5 alpha, 6 beta-triol (triol) and cholesterol-5 alpha, 6 alpha
      epoxide (epoxide) for 12 hours and with vehicle only as control. Total mRNAs were
      extracted and electrophoresed. Northern blot hybridization analyses were
      performed. The results showed mRNA expressions of LDLR gene were inhibited to
      16.1 +/- 4.4%, 33.8 +/- 0.6%, 42.8 +/- 1.8% and 46.9 +/- 3.9% of control by 25
      OH, 7-keto, epoxide and triol respectively. Pure cholesterol showed only minimal
      inhibition. The inhibitions were time dependent. Although cholesterol oxides have
      been shown to alter many membrane-related functions and the LDLR domain are
      located in the cell membrane. The findings of this study suggested that the
      cholesterol oxides exerted their repressive actions on LDLR function primarily by
      down-regulating LDLR gene expression rather than directly upon cell membrane.

PMID- 8864250
TI  - Intracellular ionized calcium ([Ca++]i) mobilization in platelets from rats
      receiving atherogenic lipids. Modulation by nifedipine.
AB  - Atherosclerosis is a progressive disease in which its clinical sequelae are
      manifest with increasing frequency as individual age. The present study seeks to
      better understand the mechanisms underlying this process by utilizing our
      previously-characterized rat model of early atherosclerosis induction to evaluate
      the effect of atherogenic plasma lipids on intracellular ionized calcium levels
      in rat platelets. Sprague-Dawley male rats were infused i.v. with 20% Lipofundin
      S, a triglyceride-rich emulsion shown by us in previous studies to induce early
      athero-sclerosis and platelet hyperactivity. Twenty four hrs after the last
      infusion, blood was obtained by cardiac puncture. Washed platelets were loaded
      with aequorin, stimulated with ADP, and [Ca++]i was determined by measuring
      luminescence in platelets from lipid-infused vs. control rats. In platelets
      isolated from lipid-infused rats, [Ca++]i levels were 34% higher (p < or = 0.05)
      than in platelets from control animals. In addition, the mean, median, and mode
      diameters of platelets from lipid-treated rats were significantly greater (p < or
      = 0.001) than those of platelets from controls. With ADP as the aggregating
      agent, nifedipine at 1 microgram/ml caused a 27% (p < or = 0.05) inhibition of
      [Ca++]i release in platelets from lipid-treated rats, but showed no inhibitory
      action in platelets isolated from control animals. Hyperlipidemia results in
      elevated platelet [Ca++]i levels, with a concomitant increase in cell size, both
      indicating enhanced platelet function. Nifedipine modulates this increased
      activity in platelets isolated from lipid-infused rats, but not in cells from
      control animals.

PMID- 8864251
TI  - Endothelial, haemostatic and haemorheological modifications in migraineurs.
AB  - Vasotropic, haemostatic and haemorheological parameters have been investigated in
      17 patients suffering from migraine without aura in comparison with 11 sex and
      age matched healthy control subjects. NO metabolites (NO2- and NO3-), endothelin
      (ET-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI
      1), fibrinogen, D-dimer, fibrinopeptide A, beta thromboglobulin (beta-TG), blood
      viscosity, plasma viscosity, haematocrit (Htc) and red blood cell (RBC)
      filterability index (FI) were determined during headache free periods.
      Migraineurs NO3- and ET-1 plasma levels, compared to control values, showed a
      significant decrease and increase respectively; fibrinogen, beta-TG and D-dimer
      appeared slightly lowered in migraineurs, while Htc remained in the normal
      limits; tPA, PAI-1 and FI were significantly reduced, while fibrinopeptide A,
      blood viscosity and plasma viscosity at a low shear rate (shr) exhibited a
      significant rise. Data obtained support the involvement of endothelial,
      haemostatic and haemorheological functions in the pathogenesis of migraine.

PMID- 8864252
TI  - Relation of C4b-binding protein to athero-sclerosis of the descending thoracic
      aorta.
AB  - C4b binding protein (C4bp) is a regulator of the classical pathway of the
      complementing system. It forms a complex with protein S which serves as a
      cofactor of coagulation inhibitor, protein C. We have reported that C4bp is an
      acute phase reactant and associated with total cholesterol and triglyceride
      concentrations (Biochim. Biophys. Acta 963 (1988) 98-108). This suggests a
      possible association of C4bp with athero-sclerosis. We examined the relation of
      C4bp levels and the severity of atherosclerosis of the descending thoracic aorta
      in 98 Japanese men. The severity of aortic atherosclerosis was assessed by
      average sclerotic length (ASL) and average sclerotic area (ASA), using
      transesophageal echocardiography. After adjustment for age, C4bp levels increased
      significantly with increasing ASL and ASA. The association remained significant
      even after adjusting for total cholesterol, hypertension, smoking, drinking, body
      mass index, fasting blood sugar, and uric acid. Immunohistochemical analysis of
      specimens of the descending thoracic aorta from autopsies, demonstrated the
      presence of C4bp in the foamy macrophages of fatty streaks and the necrotic core
      of atheromatous plaque. These findings indicate that the serum level of C4bp can
      serve as an independent indicator of aortic athero-sclerosis.

PMID- 8864253
TI  - Audioscan: a high-definition audiometry technique based on constant-level
      frequency sweeps--a new method with new hearing indicators.
AB  - The resolution of data given by traditional fixed-frequency tone audiometry is
      limited to the number of frequencies tested. Numerical electronics now allow us
      to bypass the difficulties of controlled-level frequency sweeping. The Audioscan
      method gives a detailed audiometric curve and is designed to detect even the
      narrowest notches. The Audioscan method includes the possibility of defining
      hearing loss indicators containing more information and of increasing the
      diagnostic power of the audiometry. The applications both in the clinic and in
      screening are highly promising.

PMID- 8864254
TI  - 'Derived nonlinear' versus 'linear' click-evoked otoacoustic emissions.
AB  - Recordings of emission evoked in response to transient stimuli (TEOAE) are
      partially contaminated by the initial stimulus artifact. For this reason, a
      nonlinear estimation method is widely used (derived nonlinear response, DNLR).
      The aims of this paper are: (1) to analyse some very basic properties of the
      derived nonlinear emissions such as the short-time input/output relationships;
      and (2) to show similarities and differences between the classical averaging
      (linear) and the derived nonlinear recording techniques, in the same ears, both
      in time and in the frequency domain. At latencies greater than about 6 ms,
      responses which are recorded using the derived nonlinear technique exhibit no
      additional features in comparison with linear recordings, at all stimulus levels.
      At latencies less than 6 ms, the derived nonlinear technique greatly reduces the
      linear content of the acoustic artifact, and the response may be considered as
      the initial part of the emission. However, the derived nonlinear responses tend
      to be considerably noisier than the linear emissions, thus reducing the
      effectiveness of the technique. The linear responses show a strikingly similar
      frequency content with respect to the derived nonlinear responses, at least at a
      high stimulus level and around the main peaks of the spectrum.

PMID- 8864255
TI  - Epidemiological evaluation of hearing damage related to strongly amplified music
      (personal cassette players, discotheques, rock concerts)--high-definition
      audiometric survey on 1364 subjects.
AB  - Listening to loudly amplified music can be responsible for hearing damage of the
      same nature as that caused by industrial noise. This study of the repercussions
      on hearing is based on isolating different types of risks (PCPs (personal
      cassette players), discotheques and rock/variety concerts) using 'pure' exposed
      groups matched subject to subject for age and sex to control groups. Hearing is
      studied with high-definition audiometry and an 'auditory suffering' indicator.
      Although discotheque patrons present on average no audiometric damage (211
      subjects), a statistically significant increase of average hearing thresholds is
      found in young people using a PCP > 7 h/week (54 subjects) compared to those
      using one 2-7 h/week (195 subjects) and compared to their matched controls. The
      same is true for subjects who go to rock concerts at least twice a month (87
      subjects) compared to their matched controls. Signs of auditory suffering are
      found in two subjects out of three in this last exposure group, as opposed to 12%
      of the controls. Measures to conserve young people's hearing must include a
      reduction of sound levels, the education of music and entertainment
      professionals, and making PCP users better informed.

PMID- 8864256
TI  - Influence of acquisition parameters on the measurement of click evoked
      otoacoustic emissions in neonates in a hospital environment.
AB  - There is much interest in the introduction of a universal neonatal hearing
      screening programme. Screening programmes using high-risk criteria have been used
      for some time, but 50 per cent of deaf and hearing-impaired neonates are not
      identified because they are not classified as high risk for hearing impairment at
      birth. Otoacoustic emission (OAE) measurement is widely regarded as a technique
      likely to be suitable for universal hearing screening. To examine this,
      otoacoustic emissions were measured from 351 neonate ears at a large maternity
      hospital. Of particular interest were the practicalities of recording OAE in a
      hospital environment, the establishment of an appropriate age at which screening
      should be performed on neonates and investigation of the relative advantages of
      different recording techniques. Main findings were: (1) low OAE levels relative
      to noise during the first 24 to 48 hours post partum; (2) lower OAE signal to
      noise levels in low frequencies irrespective of age; (3) increase of overall
      signal to noise ratio in frequencies above 1 kHz through the use of a shortened
      response window; and (4) OAE recording could be performed easily in mothers'
      hospital rooms prior to discharge.

PMID- 8864257
TI  - The effect of neonatal universal hearing screening in a health surveillance
      perspective--a controlled study of two health authority districts.
AB  - The contribution describes the effect of a neonatal hearing screening program in
      terms of estimated prevalence rate of congenital hearing impairment and age at
      identification in two five-year cohorts born between 1990 and 1994 as a function
      of health authority districts (HADs). In addition, identically defined five-year
      birth cohorts from 1970 to 1974 and 1980 to 1984 living in the same HADs
      evaluated previously are used in the analysis, offering longitudinal data. In
      1990 a non-targetted neonatal hearing screening program based on EOAE was
      introduced in the County-HAD, whereas the City-HAD continued its child hearing
      health surveillance program unchanged. Assuming an unchanged prevalence estimate
      of 1.5 per 1000 of congenital or early acquired (i.e. neonatal period) hearing
      disability, i.e. > or = 25 dB HL for the better ear at 0.5-4 kHz in both HADs, an
      underestimate of 68 per cent in the City and of 20 per cent in the County,
      respectively, was found at the time of data collection (January 1995).
      Significant longitudinal improvements in the early identification from the 1970
      1974 cohort compared to the 1980-1984 cohort has been demonstrated, but the
      improvement in the proportion of children identified as a function of both 6 and
      12 months of age in the 1990-1994 cohort is significantly greater, showing a
      median age at identification of 11 months in the County-HAD. The cross-sectional
      and longitudinal comparisons between the HADs imply that a neonatal universal
      hearing screening program with a 20 per cent coverage may add significantly to
      the early identification of children with early-onset hearing impairment.

PMID- 8864258
TI  - Visual and vestibular influences on head-direction cells in the anterior thalamus
      of the rat.
AB  - As a rat navigates through space, head-direction cells provide an ongoing signal
      of its momentary directional heading. This directional signal is thought to be
      generated, in part, by a dead-reckoning mechanism that uses angular motion
      information to constantly update the directional representation. This study
      investigated what kinds of angular motion information might be used for dead
      reckoning. Anterior thalamic head-direction cells were recorded from rats in a
      rotatable, cylindrical chamber, which could independently deliver visual motion
      cues and vestibular cues. Results suggest that both of these angular motion cues
      have an influence on head-direction cells and may thus be used for dead
      reckoning. The authors conclude that vestibular and visual movement cues work
      interactively, along with visual landmarks and motor signals, to determine the
      directional frame of reference.

PMID- 8864259
TI  - Psychological stress impairs spatial working memory: relevance to
      electrophysiological studies of hippocampal function.
AB  - Stress blocks hippocampal primed-burst potentiation, a low threshold form of long
      term potentiation, thereby suggesting that stress should also impair hippocampal
      dependent memory. Therefore, the effects of stress on working (hippocampal
      dependent) and reference (hippocampal-independent) memory were evaluated. Rats
      foraged for food in seven arms of a 14-arm radial maze. After they ate the food
      in four of the seven baited arms, they were placed in an unfamiliar environment
      (stress) for a 4-hr delay. At the end of the delay they were returned to the maze
      to locate the food in the 3 remaining baited arms. Stress impaired only working
      memory. Stress interfered with the retrieval of previously stored information
      (retrograde amnesia), but did not produce anterograde amnesia. Stress appears to
      induce a transient disruption of hippocampal function, which is revealed
      behaviorally as retrograde amnesia and physiologically as a blockade of synaptic
      plasticity.

PMID- 8864260
TI  - Cognitive gender differences in very young children parallel biologically based
      cognitive gender differences in monkeys.
AB  - Infant humans were trained on 2 cognitive tests that have previously revealed, in
      infant monkeys, a double dissociation that was reversible by perinatal
      manipulations of androgens and ablations of specific brain sites. Children showed
      the same sex-linked behavior found with infant monkeys: young boys were superior
      on the object reversal task and young girls were superior on the concurrent
      discrimination task. As happened previously with infant monkeys, the gender
      difference was not apparent in older human subjects. Thus, early in ontogeny,
      cognitive gender differences have now been discovered in both humans and monkeys,
      probably a result of gender differences in androgens that influence the
      maturation rate of specific brain systems.

PMID- 8864261
TI  - Cortico-hippocampal representations in simultaneous odor discrimination: a
      computational interpretation of Eichenbaum, Mathews, and Cohen (1989).
AB  - A previous model of hippocampal region function in classical conditioning is
      generalized to H. Eichenbaum, A. Fagan, P. Mathews, and N.J. Cohen's (1989) and
      H. Eichenbaum, A. Fagan, and N.J. Cohen's (1989) simultaneous odor discrimination
      studies in rats. The model assumes that the hippocampal region forms new stimulus
      representations that compress redundant information while differentiating
      predictie information; the piriform (olfactory) cortex meanwhile clusters similar
      and co-occurring odors. Hippocampal damage interrupts the ability to
      differentiate odor representations, while leaving piriform-mediated odor
      clustering unchecked. The result is a net tendency to overcompress in the
      lesioned model. Behavior in the model is very similar to that of the rats,
      including lesion deficits, facilitation of successively learned tasks, and
      transfer performance. The computational mechanisms underlying model performance
      are consistent with the qualitative interpretations suggested by Eichen baum et
      al. to explain their empirical data.

PMID- 8864262
TI  - Subicular lesions disrupt but do not abolish classically conditioned bradycardia
      in rabbits.
AB  - Rabbits and rats received horseradish peroxidase injections in the medial
      prefrontal cortex, and retrograde labeling was examined in the hippocampus (HC)
      and subicular complex (SC). Labeled cells were observed in HC and SC in the rat,
      but only in the SC of the rabbit. In a second experiment, separate groups of
      rabbits with sham, SC, or cortical control lesions were subjected to differential
      classical heart rate conditioning, in which 4-s, 75-db tones served as
      conditioned stimuli and a 3-mA paraorbital shock was the unconditioned stimulus.
      Although conditioned bradycardia was obtained in animals with SC lesions, it was
      slower to develop and was much shorter in duration than in the cortical and sham
      control groups. In the animals with SC lesions, the bradycardiac response was
      quickly replaced with tachycardia, suggesting a sympathetic bias in these
      animals.

PMID- 8864263
TI  - Retrograde abolition of conditional fear after excitotoxic lesions in the
      basolateral amygdala of rats: absence of a temporal gradient.
AB  - The role of the basolateral amygdala (LA) in the acquisition and expression of
      Pavlovian fear conditioning was examined in 80 rats. Excitotoxic lesions were
      made in the BLA using N-methyl-D-aspartate 7 days before or 1, 14, or 28 days
      after Pavlovian fear conditioning. Conditioning consisted of three pairings of a
      tone with an aversive footshock in a novel chamber, and freezing behavior served
      as an index of conditional fear. BLA lesions abolished conditional freezing to
      both the contextual and acoustic conditional stimuli at all training-to-lesion
      intervals, and the magnitude of the impairment did not vary as a function of the
      training-to-lesion interval. Reacquisition training elevated levels of freezing
      in rats with BLA lesions but did not reduce the magnitude of their deficit in
      relation to that of controls. These results reveal that neurons in the BLA have
      an enduring role in the expression of conditional fear.

PMID- 8864264
TI  - Neural systems for the expression of hypoalgesia during nonassociative fear.
AB  - A single brief exposure to moderately intense while noise is sufficient to
      produce opioid-mediated antinociception in rats. This form of stress-induced
      hypoalgesia represents a response to unconditional fear or anxiety. Three
      experiments compared the neural circuits responsible for learned versus unlearned
      fear responses. Male rats received lesions of the medial geniculate nucleus,
      lateral or central nuclei of the amygdala, or the ventral, dorsal lateral, or
      dorsal medial periaqueductal gray (PAG). Controls showed a pronounced elevation
      in tail-flick latency following presentation of 90-dB white noise. All lesions,
      with the exception of dorsolateral and dorsomedial PAG, significantly blocked
      this response. These results support the idea that hypoalgesia produced by
      aversive auditory stimuli uses a common neural circuit regardless of whether the
      response is a product of associative learning or unconditional fear/anxiety.

PMID- 8864265
TI  - Gustatory thalamus lesions in the rat: I. Innate taste preferences and aversions.
AB  - Two experiments examined the innate taste preferences and aversions of rats with
      electrolytic lesions of the gustatory thalamus (GT). Contrary to previous
      research, GT lesions had only a minor influence on intake of the 4 basic tastes
      as assessed with the 24-hr, 2-bottle preference test in Experiment 1. The same
      lesioned rats, when tested with the same stimuli in the 15-min, single-bottle
      procedure in Experiment 2, showed normal consumption patterns except for sucrose
      intake, which was attenuated. The conflicting findings of previous and present
      research are considered to result from differences in lesion size. The current
      data suggest that the GT has a relatively minor functional role in the
      unconditioned acceptance or rejection of sapid stimuli.

PMID- 8864267
TI  - Flavor and the frontal cortex.
AB  - Rats were trained to discriminate an aqueous compound of an odor and taste (amyl
      acetate and NaCl) from the components of the compound before removal of one
      olfactory bulb and the contralateral ventrolateral frontal cortex. In
      postoperative tests, experimental rats performed much more poorly than
      nonlesioned controls or controls which had all lesions made in the same
      hemisphere. However, there were no significant differences among groups on tests
      for detection of amyl acetate and NaCl. These results provide evidence that
      integration of taste and smell in the production of flavor occurs in the
      ventrolateral frontal cortex.

PMID- 8864266
TI  - Gustatory thalamus lesions in the rat: II. Aversive and appetitive taste
      conditioning.
AB  - The learning capacities of rats with electrolytic lesions of the gustatory
      thalamus (GT) were investigated in 3 experiments. In Experiment 1, the presence
      of a taste cue failed to overshadow odor aversion learning in the lesioned rats,
      yet these same animals acquired normal taste and odor aversions. Thalamic lesions
      had no discernible effect on the acquisition of a conditioned flavor preference
      in Experiment 2. Finally, GT lesions completely reversed the anticipatory
      contrast effect shown by control subjects in Experiment 3. These results suggest
      that damage to the GT spares taste detection and recognition and simple
      associative learning but interferes with learning that involves more complex
      gustatory information processing.

PMID- 8864268
TI  - Destruction of the medial forebrain bundle caudal to the site of stimulation
      reduces rewarding efficacy but destruction rostrally does not.
AB  - Rats with an electrode in the medial forebrain bundle (MFB) in or near the
      ventral tegmental area and another at the level of the rostral hypothalamus
      sustained large electrolytic lesions at either the rostral or the caudal
      electrode. The rewarding efficacy of stimulation through the other electrode was
      determined before and after the lesion. Massive damage to the MFB in the rostral
      lateral hypothalamus (LH) generally had little effect on the rewarding efficacy
      of more caudal stimulation, whereas large lesions in the caudal MFB generally
      reduced the rewarding efficacy of LH stimulation by 35-60%. Similar reductions
      were produced by knife cuts in the caudal MFB. These results appear to be
      inconsistent with the hypothesis that the reward fibers consist either of
      descending or ascending fibers coursing in or near the MFB. It is suggested that
      the reward fibers are collaterals from neurons with both their somata and their
      behaviorally significant terminals located primarily in the midbrain.

PMID- 8864269
TI  - Neonatal exposure to cocaine enhances the reward-potentiating properties of the
      drug in young adult animals.
AB  - Either cocaine (20 mg/kg) or saline vehicle was administered to rat pups once
      daily on postnatal days 1-8. The enhancement of brain stimulation reward (BSR) by
      acute administration of cocaine (2.5, 5, and 10 mg/kg i.p.) was assessed in adult
      offspring (70-90 days of age) using a rate-frequency curve-shift paradigm. Acute
      administration of cocaine produced orderly dose-related shifts of the rate
      frequency function toward lower frequencies in all groups indicating a reward
      enhancing effect of the drug on BSR. However, offspring neonatally exposed to
      cocaine displayed a greater drug-induced potentiation of BSR. Of particular note,
      the small but significant enhancement of the reward-potentiating properties of
      cocaine was more pronounced in female offspring neonatally exposed to the drug.
      These findings indicate that the rewarding properties of cocaine were altered by
      neonatal exposure to the drug in a sexually dimorphic fashion.

PMID- 8864270
TI  - Differential behavioral response to dopamine D2 agonists by sexually naive,
      sexually active, and sexually inactive male rats.
AB  - This study was performed with male rats categorized as sexually naive (SN),
      sexually active (SA), or sexually inactive (SI). In a first experiment the
      effects of dopamine (DA) D2 agonist SND 919 (0.05, 1, and 10 mg/kg) on the
      copulatory behavior of SN, SA and SI rats were assessed. In a second experiment
      the DA D2 agonist B-HT 920 (0.2 mg/kg) was used, and examination was limited to
      SN and SA rats. The effects exerted on stretching-yawning, penile erection, and
      sedation by the same compounds at the same doses in these three rat categories
      were also investigated. The main findings were that SND 919 and B-HT 920
      facilitated ejaculation in SA rats, and that the rats that were different as
      regards level of sexual activity exhibited different behavioral responses to the
      two DA agonists.

PMID- 8864271
TI  - Increases in vocalization and motor reflex thresholds generated by the
      intrathecal administration of serotonin or norepinephrine.
AB  - The capacity of serotonin and norepinephrine to elevate the thresholds of spinal
      motor reflexes (SMRs), vocalizations during shock (VDSs), and vocalization
      afterdischarges (VADs) when administered into the spinal subarachnoid space was
      evaluated. Both monoamines generated dose-dependent increases in the thresholds
      of all 3 responses. The minimum effective doses of serotonin and norepinephrine
      that elevated all 3 response thresholds were 40 micrograms and 1 microgram
      respectively. Monoamine-induced increases in response thresholds were reversed by
      the intrathecal administration of their corresponding receptor antagonists
      (phentolamine or methysergide). Threshold increases generated by serotonin were
      also partially reduced by phentolamine. These results indicate that dorsal horn
      neurons that underlie flexion reflex generation (SMR) and the rostral
      transmission of pain information (VDS and VAD) have similar thresholds of
      inhibition to spinopetal monoaminergic projections.

PMID- 8864272
TI  - Central implants of dilute estradiol enhance the satiety effect of CCK-8.
AB  - The following studies evaluated whether direct placement of estradiol into
      different brain areas could increase the satiating potency of CCK in female rats.
      In Experiment 1, estradiol implants in the PVN, but not in the VMN or third
      ventricle, significantly enhanced the satiety actions of CCK (5.0 micrograms/kg).
      In Experiment 2, a lower dose of CCK (0.5 micrograms/kg) suppressed food intake
      in females with estradiol implants in the PVN but not in animals with implants in
      the VMN or preoptic area. In both experiments, estradiol implants in the PVN
      significantly lowered food intake and body weight during the 2-day period of
      hormone treatment. Implants in other areas had no significant effects on feeding
      or body weight. These data support the hypothesis that the satiety effect of CCK
      is enhanced by estradiol and suggest that the PVN is involved in the interaction
      between CCK and estradiol.

PMID- 8864273
TI  - Hippocampal lesions impair memory for location but not color in passerine birds.
AB  - The effects of hippocampal complex lesions on memory for location and color were
      assessed in black-capped chickadees (Parus atricapillus) and dark-eyed juncos
      (Junco hyemalis) in operant tests of matching to sample. Before surgery, most
      birds were more accurate on tests of memory for location than on tests of memory
      for color. Damage to the hippocampal complex caused a decline in memory for
      location, whereas memory for color was not affected in the same birds. This
      dissociation indicates that the avian hippocampus plays an important role in
      spatial cognition and suggests that this brain structure may play no role in
      working memory generally.

PMID- 8864274
TI  - Lack of a temporal gradient of retrograde amnesia following NMDA-induced lesions
      of the basolateral amygdala assessed with the fear-potentiated startle paradigm.
AB  - M. Kim and M. Davis (1993b) previously reported that electrolytic lesions of the
      central nucleus of the amygdala, made 6 or 30 days after training, completely
      blocked the expression of fear-potentiated startle in rats. The present study
      shows that excitotoxic lesions of the basolateral amygdala also block fear
      potentiated startle and do so whether the lesions are made soon (i.e., 6 days) or
      long (i.e., 30 days) after training. The relevance of these findings to various
      theories of amygdala function is discussed.

PMID- 8864275
TI  - Recovery from habituation in Caenorhabditis elegans is dependent on interstimulus
      interval and not habituation kinetics.
AB  - The habituation of the tap withdrawal reflex of Caenorhabditis elegans was
      assessed to determine whether the kinetics of recovery from habituation were
      dependent on the interstimulus interval (ISI) used during habituation training,
      or alternately, on the rate and asymptotic level of habituation produced at a
      given ISI. Two groups of intact animals were trained at either a 10-s (CON10) or
      a 60-s (CON60) ISI. Laser ablation was used to alter the habituation kinetics in
      one further group of animals (PLM10), independent of ISI. Although the PLM10
      animals trained at a 10-s ISI habituated like CON60 worms, the recovery from
      habituation of the PLM10 animals very closely resembled the recovery of the CON10
      worms. Thus recovery kinetics are dictated by consequences of a given ISI, which
      do not impact upon habituation rate and asymptote. This suggests the recruitment
      of multiple ISI-dependent processes during habituation in C. elegans.

PMID- 8864276
TI  - Taste aversion learning in fyn mutant mice.
AB  - Conditioned taste aversion (CTA) learning is a robust form of classical
      conditioning in which animals rapidly associate a flavor with aversive internal
      symptoms. The present study assessed CTA learning in transgenic mice deficient in
      a specific nonreceptor tyrosine kinase (the fyn mutant). Fyn mutants show
      impaired long-term potentiation and marked deficits in acquisition of spatial
      learning tasks. To assess whether they are also impaired in CTA learning, fyn
      mutant and wild-type mice received 2 conditioning trials consisting of access to
      a flavored solution followed by administration of LiCl. Fyn mutant mice acquired
      significant CTAs following a single conditioning trial and these aversions were
      comparable to those seen in wild-type mice. These results indicate that the fyn
      mutation does not interfere with the acquisition of CTAs and hence that this
      mutation is not associated with a global learning deficit.

PMID- 8864277
TI  - Long-lasting transneuronal changes in rat dentate granule cell dendrites after
      entorhinal cortex lesion. A combined intracellular injection and electron
      microscopy study.
AB  - Following entorhinal cortex lesion, inhibitory hippocampal neurons show a
      persistent rarefication of those dendrites formally receiving entorhinal input.
      Physiological data indicate a long lasting disequilibrium of inhibition and
      excitation in the de-entorhinated hippocampus. We analyzed the intracellularly
      stained dendritic tree of de-entorhinated excitatory rat granule cells. Granule
      cells of controls and animals surviving 2, 8, 60 and 270 days after unilateral
      entorhinal cortex lesion were impaled. Dendrites of control cells were of typical
      shape, traced to the hippocampal fissure and a complete dye filling of dendrites
      was ascertained by EM-analysis. Conversely, 60 and 270 days following lesioning,
      dendrites were only rarely seen to extend into the outer portions of the
      molecular layer and the dendritic architecture became significantly rarefied.
      Sixty days post-lesion, intracellularly filled dendrites extending to the middle
      molecular layer were surrounded by cell clusters resembling glia. Some of these
      contained the neuronally applied dye, suggesting a close association of the
      cytosolic compartments with the altered dendrites. These observed alterations
      exceed the process of sprouting and de novo synaptogenesis of remaining afference
      for long periods of time. The dendritic morphology of both inhibitory and
      excitatory neurons seems to require specific input from the entorhinal cortex.
      Moreover, sprouting of remaining afferents is apparently not sufficient to
      compensate for this loss of input.

PMID- 8864278
TI  - Overexpression of the EGF receptor and p53 mutations are mutually exclusive in
      the evolution of primary and secondary glioblastomas.
AB  - Glioblastoma multiforme, the most malignant human brain tumor, may develop de
      novo (primary glioblastoma) or through progression from low-grade or anaplastic
      astrocytoma (secondary glioblastoma). We present further evidence that primary
      and secondary glioblastomas constitute distinct disease entities which develop
      through the acquisition of different genetic alterations. We analyzed p53
      mutations, p53 protein accumulation and epidermal growth factor receptor (EGFR)
      overexpression in 49 biopsies classified as primary or secondary glioblastoma
      according to clinical and histopathologic criteria. Patients with primary
      glioblastoma were selected on the basis of a clinical history of less than 3
      months and histopathologic features of glioblastoma at the first biopsy (19
      cases; mean age, 55 years). The diagnosis of secondary glioblastomas required at
      least two biopsies and clinical as well as histologic evidence of progression
      from low grade or anaplastic astrocytoma (30 cases; mean age, 39 years). DNA
      sequence analysis showed that p53 mutations were rare in primary glioblastomas
      (11%) while secondary glioblastomas had a high incidence of p53 mutations (67%),
      of which 90% were already present in the first biopsy. The incidence of p53
      protein accumulation (nuclear immunoreactivity to PAb 1801) was also lower in
      primary (37%) than in secondary glioblastomas (97%). In contrast,
      immunoreactivity for the EGF receptor prevailed in primary glioblastomas (63%)
      but was rare in secondary glioblastomas (10%). Only one out of 49 glioblastomas
      showed EGFR overexpression and a p53 mutation. These data indicate that
      overexpression of the EGF receptor and mutations of the p53 tumor suppressor gene
      are mutually exclusive events defining two different genetic pathways in the
      evolution of glioblastoma as the common phenotypic endpoint.

PMID- 8864279
TI  - Neuronal ceroid-lipofuscinosis--late-infantile or Jansky-Bielschowsky type-
      revisited.
AB  - The tissues from three patients with late-infantile NCL originally described by
      Max Bielschowsky became available to apply modern techniques such as fluorescence
      microscopy, electron microscopy and immunohistochemistry. While regular
      tinctorial preparations of the tissues documented a neuronal storage disorder in
      all three patients' tissues, the accumulated material proved to be
      autofluorescent, showed the ultrastructure of curvilinear lipopigments, and
      reacted strongly with an antibody against the subunit-C of mitochondrial ATP
      synthase, a major component of lipopigments in NCL and also with an antibody
      against sphingolipid activator proteins. Thus, these modern morphological
      techniques demonstrated that the originally described three siblings with late
      infantile "amaurotic familial idiocy" really had neuronal ceroid-lipofuscinosis
      of the late-infantile or Jansky-Bielschowsky type, according to current
      diagnostic criteria. This type of archival study may also contribute to the
      mosaic of medical history.

PMID- 8864281
TI  - Biochemistry of demyelination.
AB  - The myelin sheath, a lipid-rich multilamellar membrane of relative stability,
      both insulates and enhances conduction in nerve axons. A notable feature of
      myelin-specific proteins, in particular myelin basic protein, is their
      susceptibility to proteolytic activity and their encephalitogenicity, which
      induces inflammatory demyelination in the CNS. The final common pathway of myelin
      breakdown in vivo is well documented and there is evidence that myelin disruption
      can be mediated directly by soluble (circulating) factors and for following
      receptor-driven phagocytosis by macrophages. However the exact mechanism(s) of
      demyelination in multiple sclerosis is still unresolved, both antigen-specific
      and--non-specific events having the potential to generate the myelinolytic
      process.

PMID- 8864282
TI  - Mechanisms of immune injury in multiple sclerosis.
AB  - In this review, we address current concepts regarding the mechanisms of tissue
      damage that lead to demyelination and oligodendrocyte loss in multiple sclerosis.
      Particular emphasis has been placed on examining the MS lesion for evidence for
      pathogenetic processes that have been implicated from various in vivo and in
      vitro model systems. Central in this analysis has been the evaluation of the
      various effector cell types and their products. The results strongly support the
      conclusion that proinflammatory cytokines are major mediators of tissue damage,
      through the activation of inflammatory cells and resident glial cells. A role for
      antibody is also discussed, particularly as part of an antibody-dependent cell
      mediated demyelinating process. Minor populations of lymphocytes may also
      participate by defining the nature of the immunological microenvironment.

PMID- 8864283
TI  - Distinct patterns of multiple sclerosis pathology indicates heterogeneity on
      pathogenesis.
AB  - Multiple sclerosis is an inflammatory demyelinating disease of the central
      nervous system. The hallmark of its pathology is the demyelinated plaque with
      reactive glial scar formation. However, a detailed analysis of the patterns of
      demyelination, oligodendroglia cell pathology and the reaction of other tissue
      components suggests that the pathogenesis of myelin destruction in this disease
      may be heterogeneous. In this review we present a new classification scheme of
      lesional activity on the basis of the molecular composition of myelin degradation
      products in macrophages. When these criteria are used, different patterns of
      demyelination can be distinguished, including demyelination with relative
      preservation of oligodendrocytes, myelin destruction with concomitant and
      complete destruction of oligodendrocytes or primary destruction or disturbance of
      myelinating cells with secondary demyelination. Furthermore, in some cases a
      primary selective demyelination may be followed by a secondary oligodendrocyte
      loss in the established lesions. Finally, some extraordinarily severe conditions
      may result in destructive lesions with loss of myelin, oligodendrocytes, axons
      and astrocytes. This heterogeneity of plaque pathology is discussed in the
      context of recent experimental models of inflammatory demyelination, which show
      that different immunological pathways may lead to the formation of demyelinated
      plaques that reveal the diverse structural aspects described above. Our data
      indicate, that the demyelinated plaques of multiple sclerosis may reflect a
      common pathological end point of a variety of different immunological mechanisms
      of myelin destruction in this disease.

PMID- 8864284
TI  - Lymphocyte targeting of the central nervous system: a review of afferent and
      efferent CNS-immune pathways.
AB  - The central nervous system (CNS) in considered to be an immunological privileged
      site. However, inflammatory reactions in response to virus infections, in
      multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE)
      suggest that there are definite connections between the CNS and the immune
      system. In this review, we examine evidence for afferent and efferent pathways of
      communication between the CNS and the immune system, the pivotal role of regional
      lymph nodes in T-cell mediated autoimmune disease of the CNS, and the factors
      involved in lymphocyte targeting of the CNS. Afferent pathways of lymphatic
      drainage of the brain are well established in a variety of species, especially
      rodents. Fluid and antigens appear to drain along perivascular spaces populated
      by immunocompetent perivascular cells. Drainage pathways connect directly via the
      cribriform plate to nasal lymphatics and cervical lymph nodes. Soluble antigens
      draining from the brain induce antibody production in the cervical lymph nodes.
      Using a model of cryolesion-enhanced EAE, we review the role of lymphatic
      drainage and cervical lymph nodes in the enhancement of cerebral EAE. If a brain
      wound in the form of a cryolesion is produced 8 days post inoculation (dpi) of
      antigen in the induction of acute EAE, there is a 6-fold increase in severity of
      cerebral EAE by 15 dpi. Removal of the cervical lymph nodes significantly reduces
      such enhancement of EAE. These findings suggest that drainage of antigens from
      the brain to the cervical lymph nodes, in the presence of activated lymphocytes
      in the meninges or CNS, results in an enhanced second wave of lymphocytes
      targeting the brain. In examining the efferent immune pathway by which
      lymphocytes home to the CNS, several studies have characterized the phenotype of
      infiltrating T lymphocytes by the use of immunocytochemistry or FACS analysis. T
      cells infiltrating the CNS are recently activated/memory lymphocytes typified by
      their high expression of CD44, LFA-1 and ICAM-1 and low expression of CD45RB in
      the mouse. Following the induction of EAE in susceptible mice, ICAM-1 and VCAM-1
      are dramatically upregulated on CNS vessels; lymphocytes bind to such vessels via
      the interaction of their known ligands, LFA-1/Mac-1 and alpha 4-integrins, at
      least in vitro. It appears that alpha 4-integrin plays a key role in lymphocyte
      recruitment across the blood-brain barrier and may be a major factor in
      lymphocyte targeting of the CNS. Definition of factors involved in the afferent
      and efferent connections between the CNS and the immune system may clarify
      mechanisms involved in immune privilege of the CNS and may open significant
      therapeutic opportunities for multiple sclerosis.

PMID- 8864285
TI  - Genetics of demyelinating diseases.
AB  - Multiple sclerosis (MS), the prototypic demyelinating disease in humans, is the
      most common cause of acquired neurological dysfunction arising between early to
      mid adulthood. MS is an inflammatory disorder and is believed to result from an
      autoimmune response, directed against myelin proteins and perhaps other antigens,
      resulting in demyelination and dense astrogliosis. A genetic component in MS is
      indicated by an increased relative risk to siblings compared to the general
      population (lambda s) of 20-40, and an increased concordance rate in monozygotic
      compared to dizygotic twins. Association and/or linkage studies to candidate
      genes have yielded a considerable number of reports showing significant genetic
      effects for the major histocompatibility complex (MHC), immunoglobulin heavy
      chain, T cell antigen receptor, and myelin basic protein loci. With the exception
      of the MHC, however, these results have been difficult to replicate or apply
      beyond isolated populations. Recently, a multi-analytical genomic screen effort
      was completed to identify genomic regions potentially harboring MS susceptibility
      genes. Nineteen such regions were identified. The data confirm the reported
      genetic effect of the MHC region. However, no single locus generated overwhelming
      evidence of linkage. These results suggest a multifactorial etiology, including
      both environmental and multiple genetic factors of moderate effect.

PMID- 8864286
TI  - Animal models of demyelination.
AB  - Demyelination is a pathological feature that is characteristic of many diseases
      of the central nervous system (CNS) including multiple sclerosis (MS), sub-acute
      sclerosing panencephalomyelitis (SSPE), metachromatic leukodystrophy and
      Pelizaeus-Merzbacher disease. While demyelination is a pathological end-point
      that is common to all of these diseases, the cellular and molecular mechanisms
      responsible for this pathology are very different . These range from genetic
      defects that affect lipid metabolism in the leukodystrophies, cytopathic effects
      of viral infection in SSPE to the action of immunological effector mechanisms in
      MS and the viral encephalopathies. Irrespective of the initial cause of myelin
      degradation, many of these disorders are associated with some degree of CNS
      inflammation, as indicated by the local activation of microglia, recruitment of
      macrophages or the intrathecal synthesis of immunoglobulin. Many of these
      phenomena are now being duplicated in animal models, providing not only new
      insights into the pathogenesis of human demyelinating diseases , but also
      unexpected interrelationships between the immune response in the CNS and the
      pathogenesis of diseases such as Alzheimers disease and HIV encephalopathy.
      Autoimmune mediated models of inflammatory demyelinating CNS disease have proved
      particularly valuable in this respect as they allow the effects of defined immune
      effector mechanisms to be studied in the absence of CNS infection.

PMID- 8864287
TI  - Regulation of oligodendrocyte development and CNS myelination by growth factors:
      prospects for therapy of demyelinating disease.
AB  - Multiple sclerosis (MS), the most common neurological disorder diagnosed in young
      adults, is characterized by autoimmune demyelination in the central nervous
      system (CNS). Promotion of remyelination in the brain and spinal cord is a
      potential strategy for therapeutic intervention in MS and other demyelinating
      diseases. Recent studies have shown that the development of oligodendrocytes, the
      myelin-forming cells of the CNS, is extensively controlled by growth factors.
      These factors regulate the proliferation, migration, differentiation, survival
      and regeneration of oligodendroglial cells and the synthesis of myelin, and often
      interact in a complex manner. Moreover, insulin-like growth factor I (IGF-I) has
      proven effective for therapy of experimental autoimmune encephalomyelitis (EAE),
      an animal model of autoimmune demyelination. In this review we summarize recent
      findings on the regulation of oligodendrocyte development and CNS myelination by
      growth factors, and discuss these findings in the context of possible clinical
      application for the therapy of neurological disease in humans.

PMID- 8864288
TI  - Central nervous system remyelination clinical application of basic neuroscience
      principles.
AB  - Studies in both humans and experimental animals have demonstrated that myelin
      repair in the CNS is a normal physiological response to myelin damage, similar to
      tissue injury elsewhere in the body. The unanswered question is why myelin repair
      is incomplete in multiple sclerosis patients. In this paper we review the
      morphological characteristics of remyelination, discuss the available animal
      models of CNS demyelination and their usefulness to identify the molecular,
      cellular, and morphological events involved in CNS myelin repair, examine the use
      of immunosuppression, immunoglobulins, protein growth factors, and glial cell
      transplantation at the primary experimental therapies designed to promote CNS
      remyelination, and address the potential electrophysiological and clinical
      benefits of myelin repair in the CNS.

PMID- 8864289
TI  - Pitfalls in the evaluation of apoptosis using TUNEL.

PMID- 8864290
TI  - Inhibition of free radical production or free radical scavenging protects from
      the excitotoxic cell death mediated by glutamate in cultures of cerebellar
      granule neurons.
AB  - Glutamate kills sensitive neurons through several steps downstream to receptor
      activation: increased free Ca2+ levels, activation of various enzymes and
      accumulation of reactive oxygen species (ROS). We have evaluated in a well
      established model of neuronal cultures the neuroprotective effects of blocking
      these mechanisms, either singularly or by combining multiple enzyme inhibition
      and/or ROS scavenging. In vitro cultures of cerebellar granule cells exposed to a
      toxic concentration of glutamate (100 microM for 15 min in the absence of Mg2+)
      combined with several pharmacological treatments. Inhibition of nitric oxide
      synthase (NOS) and phospholipase A2 (PLA2) were effective in decreasing cell
      death and the combined treatments showed some degree of additivity. By contrast,
      inhibition of xanthine oxidase (XO) with allopurinol was uneffective.
      Antioxidants (in particular vitamin e or vitamin E analogs). protected neurons up
      to more than 50%. A synergistic effect was demonstrated by the combination of
      vitamin E and C. On the other hand, antioxidants did not increase the protection
      granted by enzyme inhibitors, suggesting that they act downstream to NOS and
      PLA2. In conclusion, NOS and PLA2 activated by Ca2+ influx give rise to reactive
      oxygen species whose deleterious action can be counteracted either by inhibiting
      these enzymes or by scavenging the excess of free radicals produced by them.
      Finally, a moderate protection was obtained by blocking protein synthesis with
      cycloheximide, suggesting a partial contribution of apoptotic mechanisms to the
      excitotoxic cell death.

PMID- 8864291
TI  - The contribution of NMDA receptors to the visual response in animals that have
      been partially monocularly deprived.
AB  - Kittens were monocularly deprived to give a partial shift in the ocular dominance
      histograms from their visual cortices. Responses were measured for the normal and
      deprived eyes at a variety of contrasts, and curves fitted to give measurements
      of background activity and peak visual response. The N-methyl-D-aspartate (NMDA)
      antagonist D-2-amino-5-phosphonovalerate (APV) was then applied, and the effect
      on the contrast-response curves was measured, and compared in the two eyes. In
      normal animals, the effect of APV on the contrast-response curve was similar in
      the two eyes. In monocularly deprived animals, on average, peak visual response
      was affected similarly in the two eyes, although there was wide variability from
      cell to cell. When the effect of APV on background activity was measured, there
      was difference between the normal and deprived eyes. APV reduced background
      activity in the normal eye more than it reduced background activity in the
      deprived eye. In other words, the NMDA contribution to background activity in the
      deprived eye was reduced compared to the NMDA contribution to background activity
      in the normal eye. This could represent a reduction of NMDA receptors in the
      pathway from the deprived eye, like the reduction of acetylcholine receptors
      associated with the losing input at the neuromuscular junction before the nerve
      is eliminated.

PMID- 8864292
TI  - Immunohistochemical localization of tissue factor pathway inhibitor-1 (TFPI-1), a
      Kunitz proteinase inhibitor, in Alzheimer's disease.
AB  - Senile plaques in Alzheimer's disease (AD) are composed principally of A beta, a
      4 kDa fragment of the amyloid precursor protein (APP). Longer forms of APP which
      contain a Kunitz proteinase inhibitor (KPI) domain are elevated in aged and in AD
      brains. Tissue factor pathway inhibitor-1 (TFPI) contains three tandem KPI
      domains and has been well characterized for its role as a natural anticoagulant
      in the extrinsic coagulation pathway. Functionally, the first two KPI domains of
      TFPI bind and inhibit the activity of factor Xa and VIIa respectively. In
      addition, TFPI and APP-KPI share a common clearance mechanism through the low
      density lipoprotein receptor-related protein (LRP). As part of an ongoing study
      of the role of KPI-containing proteins in AD, the current study examines TFPI
      localization in the brain. We report here that TFPI is immunohistochemically
      localized to microglia in both AD and non-AD individuals and is localized to some
      senile plaques in AD. Western blot analyses indicate that the amount of TFPI is
      elevated in frontal cortex samples from AD brains. We propose that TFPI may play
      a cell specific role in proteinase regulation in the brain.

PMID- 8864293
TI  - Subpopulation of dogs with severe brain parenchymal beta amyloidosis
      distinguished with cluster analysis.
AB  - A study of the brains of 30 dogs, mongrels from 6.5 to 26.5 years of age,
      revealed that all dogs older than 13 years of age develop amyloid-beta-positive
      plaques. Cluster analysis based on the age of the dogs and the numerical density
      of amyloid-positive plaques stained with monoclonal antibody 4G8 (17-24aa)
      revealed that the population of old dogs consists of two subpopulations: one with
      a very low (0.8/mm2 on average) and other with a high (19.2/mm2 on average)
      numerical density of plaques. These two groups (19.5 and 19.1 years of age,
      respectively) appear to emerge from the younger group (12.2 years of age on
      average), with moderate (2.2/mm2 on average) numerical density of 4G8-positive
      plaques. These data may indicate that only a portion of the mongrel population
      (43%) is susceptible to amyloidosis beta or that only this severely affected
      subpopulation was exposed to a factor or factors inducing this pathology and
      developed severe cortical amyloidosis that correlates with age. Dog plaques are
      only of the diffuse type, with nonfibrillar, thioflavin S-, and Congo red
      negative amyloid in all groups distinguished by cluster analysis. Only from 10%
      of 4G8-positive plaques in the mildly affected group to 29% in the severely and
      37% in the moderately affected group are Bielschowsky positive. In the younger,
      moderately affected group, 6E10 (1-17aa)-positive plaques prevail. In the two old
      groups with severe and weak changes, almost all 4G8-positive plaques are also
      6E10-positive. Carboxy-terminal region immunocytochemistry reveals that BC42
      positive plaques are numerous, whereas BC40-positive plaques are few or absent.
      The differences in the silver-positivity of plaques and their immunoreactivity in
      both the amino- and carboxy-terminal regions may reflect differences in amyloid
      beta deposition and resolution. Dog parenchymal amyloidosis beta appears to be a
      model for the study of diffuse plaques.

PMID- 8864294
TI  - Roles of monoaminergic, glycinergic and GABAergic inhibitory systems in the
      spinal cord in rats with peripheral mononeuropathy.
AB  - The current study was designed to determine if the monoaminergic descending
      inhibitory system and the glycinergic and GABAergic inhibitory systems were
      activated in the spinal cord in the presence of peripheral mononeuropathy
      produced by loose ligatures around the common sciatic nerve. The time course of
      withdrawal latencies to thermal stimuli were assayed in lesioned and sham
      operated rats. The levels of monoamines (serotonin; 5-HT, noradrenaline, and
      dopamine), glycine and gamma-aminobutyric acid (GABA) in the dorsal half of the
      spinal cord were measured using HPLC with electrochemical detection. Furthermore,
      on day 7 after nerve ligation, intrathecal methysergide, yohimbine, strychnine or
      bicuculline was administered in order to investigate the roles of these
      inhibitory neuromodulators in this pathological pain state. The levels of 5-HT
      and noradrenaline significantly increased in both ipsi- and contralateral sides
      of the dorsal half of the lumbar spinal cord in the lesioned, but not sham
      operated animals. The levels of glycine and GABA in the ipsilateral dorsal half
      of the spinal cord increased significantly and were significantly higher than in
      the contralateral side. Intrathecal antagonists of 5-HT, noradrenaline, glycine
      and GABA produced enhancement of the magnitude of hyperalgesia on the lesioned
      hindpaw. We also examined the effects of four daily single treatments with
      intrathecal MK-801 beginning 15 min prior to nerve ligation on the development of
      thermal hyperalgesia and on the contents of the neuromodulators in the ligation
      model. MK-801 treatment effectively abolished the increases in 5-HT,
      noradrenaline, glycine and GABA levels as well as preventing the development of
      hyperalgesia. The results of the present study suggest that the pathological pain
      state activates or increases the activity of these inhibitory systems.

PMID- 8864295
TI  - Brain distribution of vasoactive intestinal peptide receptors following REM sleep
      deprivation.
AB  - Vasoactive intestinal peptide (VIP) has been shown to increase rapid eye movement
      (REM) sleep in normal and insomniac animals, while the administration of anti-VIP
      antibodies or an antagonist of VIP receptors decreases REM sleep. In addition,
      recently, it has been suggested that a VIP-like substance accumulates in the CSF
      during waking and that it may be involved in the production of the REM rebound
      normally seen following REM sleep deprivation. This evidence suggests that VIP
      may be important in modulating REM sleep in normal conditions and during REM
      sleep rebound. To determine whether VIP is involved in REM sleep homeostasis, VIP
      receptors of discrete brain areas was determined by autoradiography after 24 and
      72 h of REM sleep deprivation (REM SD) by the water tank technique. Since this
      procedure has been suggested to produce some stress, an additional group adapted
      for 7 days to the sleep deprivation situation was tested. The results showed that
      REM SD produces an increase in the density of VIP receptors in several brainstem
      and forebrain structures at 24 h of REM SD and more so at 72 h of REM SD.
      Interestingly, results showed that habituation to the REM SD procedure decreases
      the density of VIP receptors in some areas of the brain of the REM sleep-deprived
      rats. The results are discussed in terms of the possibility that waking induces
      an increase of VIP receptors in several structures, which in turn are responsible
      for modulating REM sleep, but that stress contributes in part to VIP receptor
      changes.

PMID- 8864296
TI  - Nerve growth factor (NGF) content in adult rat brain tissues is several-fold
      higher than generally reported and is largely associated with sedimentable
      fractions.
AB  - Initial studies had revealed that the bioactivity of nerve growth factor (NGF) in
      sonicates of adult rat hippocampal formation (HF) is several-fold greater in
      their pellet than their supernatant fractions. Such observations have prompted an
      analysis of NGF antigen (NGF-Ag) contents in pellets and supernatants from a
      variety of adult rat CNS tissues, both in the absence and the presence of
      exogenous beta-NGF. With HF tissues, NGF-Ag in the supernatants was comparable to
      most literature values, but pellet NGF-Ag was 3 to 5 times that amount. All other
      CNS tissue sonicates also revealed 3-6 fold higher NGF-Ag in their pellets than
      their supernatants, hence overall NGF-Ag contents were greatly in excess of
      reported ones. Presentation of mouse beta-NGF to a tissue, its sonicate, or its
      standard pellet resulted in a transfer to the final pellet of 30-50% of the added
      soluble NGF-Ag (and 30% of the added bioactivity). This percentage is much lower
      than that present in native pellets (80%), suggesting that the association of
      endogenous NGF with particulate matter may involve at least two compartments.
      Treatments of pellets with salt, alkaline pH, and/or the detergent Triton X-100
      have revealed a third subset, namely additional pellet NGF-Ag that was not
      initially recognized by the antibody in our ELISA assay. The treatments also
      caused substantial release of NGF from pellet to supernatant. Further studies
      should clarify the nature of the association between NGF and the three subsets of
      pellet NGF and allow the investigation of the pellet molecules responsible for
      it.

PMID- 8864297
TI  - Galanin gene expression declines with adulthood in the cholinergic fields of the
      horizontal diagonal band of male rats.
AB  - The neuropeptide galanin (GAL) influences learning and memory processes, perhaps
      by inhibiting cholinergic function. We recently reported that, in the rat, the
      nucleus of the horizontal limb of the diagonal band (HDB) exhibits the highest
      level of GAL mRNA coexpression by basal forebrain (BF) cholinergic neurons and,
      in the HDB, virtually all GAL mRNA-expressing neurons correspond to the
      cholinergic cell type. Since GAL gene expression is induced across puberty in
      many brain regions, we used in situ hybridization histochemistry and quantitative
      autoradiography to assess GAL gene expression across the rostro-caudal extent of
      the HDB in prepubertal and adult male rats and to determine whether GAL gene
      expression is also regulated during maturation in this BF region. Our results
      show that the number of GAL mRNA-expressing cells per section is significantly
      reduced in the HDB with adulthood. Post-hoc analysis indicated that these age
      associated differences in the number of GAL mRNA-expressing cells per section
      could be ascribed to the rostral and central subregions of the HDB. Age-related
      differences in the labeling intensity of GAL mRNA-expressing neurons were also
      detected in the rostral and central subregions of the HDB. No age-associated
      differences in GAL gene expression were found in the caudal HDB subregion. These
      results suggest that: (1) in contrast to other brain regions, GAL gene expression
      in the cholinergic BF may be negatively regulated by factors concomitant with
      puberty; and (2) the inhibition of cholinergic function by cosecreted GAL may be
      enhanced prior to puberty within cholinergic neurons of the rostral and central
      aspects of the HDB.

PMID- 8864298
TI  - Effects of freezing storage time on the density of muscarinic receptors in the
      human postmortem brain: an autoradiographic study in control and Alzheimer's
      disease brain tissues.
AB  - The effect of sex, age (range = 41-84 years), postmortem delay (range = 1-71 h)
      and freezing storage time (FST) (range = 8-75 months) at -25 degrees C on the
      density of muscarinic receptors (MR) was examined in tissue sections of several
      representative areas of 41 postmortem brains from adult patients who had died
      from non-neurological disorders using [3H]N-methylscopolamine as a ligand.
      Neither age, sex nor postmortem delay determined significant changes in the
      density of MR in frontal and entorhinal cortex, hippocampus and striatum. By
      contrast, FST significantly decreased the densities of MR in frontal and
      entorhinal cortex, pyramidal layer of CA1 and CA3 fields at the hippocampus and
      over caudate nucleus. This reduction in MR densities did not reach statistical
      significance, for any region, when FST was less than 39 months. Although there
      was a tendency towards a decrease, no significant changes were observed in
      putamen and over hippocampal dentate gyrus. FST (range = 11-78 months) also
      significantly decreased the densities of MR in the same regions of postmortem
      brains from 18 patients who had died with a clinico-pathological diagnosis of
      Alzheimer's disease (AD). Even though there was a general tendency towards a
      decrease (between 7% in the caudate and 30% in the dentate gyrus at the
      hippocampus), no significant differences could be seen in MR densities between
      control and AD cases, except in the hilus in the dentate gyrus (P < 0.022), when
      brains were matched for FST. From the present results it is clear that control
      and diseased brains must also be matched for FST as well as for other factors
      such as sex, age and postmortem delay. It is possible that differences in FST
      could in part account for the variability of the reported results measuring MR in
      control and AD brains. At least for MR, FST shorter than three years would seem
      to be acceptable when performing this kind of studies.

PMID- 8864299
TI  - Acoustically activated c-fos expression in auditory nuclei of the anaesthetised
      guinea pig.
AB  - The spatial expression of the immediate-early gene c-fos in central auditory
      nuclei of the anaesthetised guinea pig was investigated following exposure of the
      animal to acoustic stimulation. Accurate control of both the spectra and the
      level of the stimulus was designed so that the presumed excitation of central
      auditory nuclei was similar across animals. For unstimulated anaesthetised
      control animals levels of labelling were significantly higher when compared with
      unanaesthetised controls. This appeared to a result of the combination of the
      experimental manipulations and also the use of the anaesthetic. A surprising
      finding was that unstimulated control animals placed in an anechoic chamber
      demonstrated the highest levels of fos-like immunoreactivity (Fos-LIR). When
      anaesthetised animals were exposed to acoustic stimuli the total number of cells
      showing Fos-LIR was elevated when compared to anaesthetised, but unstimulated
      animals. There was no evidence at any level of the auditory pathway that these
      animals demonstrated spatially restricted Fos-LIR which may have suggested place
      frequency mapping. In contrast, spatially restricted labelling was found in awake
      animals exposed to an identical stimulus.

PMID- 8864300
TI  - Functional anatomy of GO/NO-GO discrimination and response selection--a PET study
      in man.
AB  - The purpose of this study was to identify the functional fields activated in
      relation to the NO-GO decision. Nine healthy subjects participated in the study
      which consisted of two test positron emission tomography (PET) scans (GO/NO-GO
      task and response selection task) and one control scan. In the response selection
      task, subjects were asked to flex their thumb of the right hand when a light
      emitting diode (LED) placed 60 cm from their eyes turned on red and to flex their
      index finger of the right hand when LED turned on green. In the GO/NO-GO task,
      subjects were asked to flex their thumb when the LED turned on red, however, they
      were asked not to move their fingers when LED turned on green. In the control
      state, they were asked simply to look at the LED without any movement of finger
      during the course of the scan. The mean regional cerebral blood flow (rCBF)
      change images for each task minus control and task minus task were calculated and
      fields of significant rCBF changes were identified. Several fields in the
      prefrontal cortex of the right hemisphere were specifically activated in relation
      to the GO/NO-GO task. The results indicate that the prefrontal cortex of the
      right hemisphere may be a key structure to make a decision not to move.

PMID- 8864301
TI  - Expression of Fos in rat brain in relation to sodium appetite: furosemide and
      cerebroventricular renin.
AB  - Two experiments were performed to investigate the relationship between the
      expression of sodium appetite and the appearance of Fos-like immunoreactivity
      (Fos-IR) in the brain of rats. In the first experiment, rats were depleted of
      sodium by treatment with furosemide 24 h prior to sacrifice and without access to
      either food or sodium solution. Some rats had access to distilled water, and
      others had no fluids available during the 24 h. All of the furosemide-treated
      rats showed Fos-IR in both the subfornical organ (SFO) and around the organum
      vasculosum laminae terminalis (OVLT). Rats with access to distilled water during
      the depletion period showed no Fos-IR in the supraoptic (SON) or paraventricular
      hypothalamic nuclei (PVN) and, in parallel behavioral studies, comparably-treated
      rats consumed only 0.3 M NaCl solution at the end of the 24 h. In rats that had
      no fluids during the deprivation period, only about one half showed Fos-IR in SON
      and PVN and, in parallel behavioral studies, comparably treated rats consumed
      both water and 0.3 M NaCl solution at the end of 24 h. In a second experiment,
      cerebroventricular administration of renin stimulated short latency intake of 0.3
      M NaCl and water. The relative intakes of water and NaCl were comparable at a low
      dose of renin, but intake of water exceeded that of NaCl after higher doses.
      Renin induced Fos-IR in SFO, MnPO, peri-OVLT region, SON and PVN. Both Fos-IR and
      fluid intake were antagonized by administration of losartan, an angiotensin II
      type 1 receptor antagonist. Thus, only the circumventricular organs of the lamina
      terminalis showed Fos-IR during each natriorexigenic regimen in these studies.
      These data support the view that Ang II of both central and peripheral origin
      activates the SFO and/or peri-OVLT region and contributes to sodium appetite.

PMID- 8864302
TI  - Cerebrocortical Fos expression following dopaminergic stimulation: D1/D2
      synergism and its breakdown.
AB  - Using standard immunohistochemical techniques, we examined Fos expression in
      different areas and layers of cerebral cortex in rats following combined or
      separate stimulation of dopamine D1 and D2 receptors under normal conditions and
      following five days of reserpine (1 mg/kg/day), a treatment that causes a
      breakdown in requisite D1/D2 synergism. In normal animals, combined but not
      separate stimulation of D1 and D2 receptors elicited Fos expression in frontal
      and parietal, but not cingulate, cortex. Expression was highest in layer IV of
      primary somatosensory cortex; in frontal and secondary somatosensory cortex, Fos
      expression was lower and peaked in layer VI. Cortical Fos expression following
      amphetamine showed the same general pattern, and was blocked by either a
      selective D1 or D2 antagonist. Following reserpine treatment, stimulation of
      either D1 or D2 receptors gave rise to cortical Fos expression in patterns
      similar to each other and to combined D1/D2 stimulation in normal rats (except in
      frontal cortex in which separate D1 or D2 stimulation was unable to elicit Fos
      even following repeated reserpine treatment). The fact that cortical Fos
      expression was tightly associated with behavioral activation together with its
      laminar and areal distribution suggest that sensory input resulting from
      behavioral activation may be an important stimulus for this immediate-early gene
      response.

PMID- 8864303
TI  - NMDA receptor activation induces glutamate release through nitric oxide synthesis
      in guinea pig dentate gyrus.
AB  - We tested the hypothesis that the release of glutamate following activation of N
      methyl-D-aspartate (NMDA) receptors is mediated by nitric oxide (NO) production,
      using slices of the guinea pig hippocampus. The NMDA-induced glutamate release
      from slices of dentate gyrus or CA1, which was both concentration-dependent and
      Ca(2+)-dependent, was also Mg(2+)-sensitive and abolished by MK-801, a selective
      non-competitive NMDA receptor antagonist. In dentate gyrus, the NMDA-induced
      glutamate release was inhibited non-significantly by tetrodotoxin, whereas the NO
      synthase (NOS) inhibitor NG-nitro-L-arginine (L-NNA) blocked the NMDA-induced
      release of glutamate in a concentration-dependent manner, but not a high K(+)
      evoked release of glutamate. In addition, the L-NNA blockade of NMDA-induced
      release of glutamate was recovered by pretreatment with L-arginine, the normal
      substrate for NOS. These results suggest that activation of NMDA receptors in
      dentate gyrus, as well as subsequent Ca2+ fluxes, is required for the neuronal
      glutamate release mediated by NO production. On the other hand, the NMDA-evoked
      glutamate release from CA1 region was tetrodotoxin-sensitive and was not
      inhibited by L-NNA, thereby suggesting that activation of NMDA receptors in CA1
      results in increased glutamate release in an NO-independent manner. Taken
      together, the NMDA receptor-mediated neuronal release of glutamate from the
      guinea pig dentate gyrus likely involves the recruitment of NOS activity.

PMID- 8864304
TI  - Nitric oxide synthase immunoreactivity distinguishes a sub-population of GABA
      immunoreactive neurons in the ventrobasal complex of the cat.
AB  - This study describes the presence of nitric oxide synthase (NOS-ir)
      immunoreactive neurons in the thalamic ventrobasal complex of the cat. NOS-ir is
      co-localized with gamma-aminobutyric acid (GABA-ir) in a subset of small neurons
      identified as local circuit neurons in previous studies. The double labeled
      neurons are further identified by a larger soma diameter when compared to GABA-ir
      only neurons. All NOS-ir somata exhibit GABA-ir but none exhibit immunoreactivity
      to calbindin.

PMID- 8864305
TI  - Kindling induces neuropsin mRNA in the mouse brain.
AB  - Neuropsin mRNA expression was analyzed and mapped in the mouse brains after
      kindling epileptogenesis by using in situ hybridization histochemistry. Dynamic
      increases of the neuropsin mRNA were observed in the layer II of prelimbic,
      somatosensory, auditory, perirhinal, entorhinal, and piriform cortices in an
      activity-dependent manner, though no neuropsin gene was expressed in these areas
      in control mice. In addition to the confirmation of our previous studies showing
      increases of mRNA in the hippocampus and amygdaloid complex, there were also
      remarkable increases of the neuropsin mRNA in the limbic areas, such as the
      accessory olfactory nucleus, the medial and lateral septal nucleus, the nucleus
      of diagonal band, the substantia innominata and the zona incerta. The dynamic
      activity-dependent changes of the gene expression and the site-specificity of
      neuropsin localization are suggesting that this molecule is implicated in
      cortical- and limbic-specific neuronal reorganization.

PMID- 8864306
TI  - Flow-cytometric estimation on glutamate- and kainate-induced increases in
      intracellular Ca2+ of brain neurons: a technical aspect.
AB  - Effects of glutamate and kainate on the intracellular Ca2+ concentration
      ([Ca2+]i) in a large population (several thousand) of dissociated cerebellar
      granule cell neurons were evaluated using a flow-cytometer and a combination of
      two fluorescent dyes, fluo-3-AM for estimating [Ca2+]i and ethidium bromide for
      removing neurons that had compromised membranes from the cell population
      examined. The number of neurons responding to glutamate or kainate in augmenting
      the fluo-3 fluorescence increased in a dose-dependent manner. The number of
      neurons responding to kainate was much greater than that to glutamate. CNQX, a
      blocker of non-NMDA receptors, completely blocked the response elicited by
      kainate while the complete blockade of this glutamate-induced response was made
      by a combination of MK-801, a NMDA receptor blocker, and CNQX. Nicardipine, a
      calcium antagonist, decreased the number of neurons responding to glutamate and
      kainate, suggesting involvement of voltage-dependent calcium channels. These
      results indicate that the flow-cytometric measurement of glutamate and kainate
      responses has the potential to provide answers to such questions as what
      percentage of the population of neurons respond to these amino acids and what is
      the resulting distribution of [Ca2+]i.

PMID- 8864307
TI  - Abnormal c-fos expression in the lateral habenula during dystonic attacks in a
      hamster model of idiopathic dystonia.
AB  - The genetically dystonic hamster (dtsz), an animal model of idiopathic dystonia,
      displays sustained twisting movements and postures either spontaneously or in
      response to mild stress. In the present study the expression of c-fos
      immunoreactive neurons (Fos-ir), used as an indicator of neuronal activity, was
      investigated within various brain regions in dtsz hamsters and non-dystonic
      control hamsters. Under baseline condition, i.e. in the absence of dystonia, the
      expression of Fos-ir did not reveal any differences between dtsz hamsters and
      controls. However, in response to mild stress several brain regions, particularly
      the lateral habenula (LHb), exhibited differences in c-fos induction in dtsz
      hamsters and controls. Whereas in the LHb the expression of Fos-ir was markedly
      enhanced in controls, it showed almost no increase in dystonic hamsters,
      indicating impaired neuronal activity. Since the lateral habenula receives major
      input from the basal ganglia via the entopeduncular nucleus, the present data
      might indicate that basal ganglia are involved in the dystonic syndrome in mutant
      hamsters.

PMID- 8864308
TI  - Age-related assessment of central 5-HT1A receptors following irreversible
      inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).
AB  - Age-dependent differences in the ability of N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ) to irreversibly inactivate 5-HT1A receptors were
      investigated in female Fischer 344 rats (ages 3 and 22 months). In the
      hippocampus, frontal cortex and amygdala, EEDQ reduced 5-HT1A receptor density
      (33-70%) and drug affinity (2.3-6.2 fold) as determined by Scatchard analyses
      using [3H]8-hydroxy-2-(di-N-propylamino)tetralin. In the frontal cortex, the
      reduction in Bmax values was significantly greater in 3 months vs. 22 months
      groups. These region-specific and age-dependent alterations in 5-HT1A receptors
      may be of pathophysiological significance in age-related cognitive decline and
      Alzheimer's disease.

PMID- 8864309
TI  - The influence of steady magnetic fields on the mouse hippocampal evoked
      potentials in vitro.
AB  - Direct current-generated EM fields modulated evoked potentials recorded from
      hippocampal slices. Both the synaptic efficiency represented by the slope of EPSP
      and the number of activated pyramidal cells represented by the population spike
      were modified by EM fields. While the weak EM fields (2-3 mT) exerted a biphasic
      effect observed as a transient small depression followed by a long-lasting
      amplification of the potentials, stronger EM fields (8-10 mT) depressed these
      potentials. This depression could be partially reversed by increasing the
      strength of the stimulation. It is suggested that EM-induced fluctuations in the
      intracellular Ca2+ concentration are responsible for the observed effect.

PMID- 8864310
TI  - Multi-centre trials: U-turns by bandwagons and the patient left by the wayside.

PMID- 8864311
TI  - Disposition of diazepam in young and elderly subjects after acute and chronic
      dosing.
AB  - 1. The pharmacokinetics of diazepam were examined in seven young (20-30 years)
      and six elderly (60-75 years) males prior to and also after chronic oral dosing
      of diazepam. 2. Following intravenous administration, the half-life and volume of
      distribution of 14C-labelled diazepam in the elderly were approximately twofold
      greater than corresponding estimates in younger subjects (mean +/- s.d., 71.5 +/-
      27.6 vs 44.5 +/- 16.5 h and 1.39 +/- 0.32 vs 0.88 +/- 0.30 1 kg-1, respectively).
      Clearance did not differ between the two groups (0.26 +/- 0.09 vs 0.29 +/- 0.09
      ml min-1 kg-1). 3. The accumulation of diazepam and its major metabolite,
      desmethyldiazepam, were extensive during chronic administration. A radioreceptor
      assay that measured total benzodiazepine activity, including diazepam and its
      active metabolites, indicated that the accumulation of 'benzodiazepine
      equivalents' was similar to the sum of the accumulated diazepam and
      desmethyldiazepam concentration levels. However, the level of 'benzodiazepine
      equivalents' on multiple-dosing was about double that of the predicted steady
      state 'equivalent' concentration from single-dose studies. This was due to the
      insensitivity of the radioreceptor assay for desmethyldiazepam following single
      dose diazepam administration. 4. There were no age- or dosing-related differences
      in diazepam clearance (0.37 +/- 0.22 vs 0.32 +/- 0.18 ml min-1 kg-1, young vs
      elderly, single-dose; 0.37 +/- 0.11 vs 0.27 +/- 0.12 ml min-1 kg-1, young vs
      elderly, multiple-dose) and no age-related differences in the levels of
      accumulated 'benzodiazepine equivalents' (243.7 +/- 60.1 vs 288.0 +/- 125.8 ng ml
      1, young vs elderly). 5. Thus, changes that occur in diazepam disposition with
      ageing after acute administration do not appear to be important during chronic
      dosing. On the other hand, accumulation of diazepam and desmethyldiazepam are
      considerable and would be expected to be clinically relevant.

PMID- 8864312
TI  - Diazepam-omeprazole inhibition interaction: an in vitro investigation using human
      liver microsomes.
AB  - 1. The metabolism of diazepam to its primary metabolites 3-hydroxydiazepam (3HDZ)
      and nordiazepam (NDZ) was evaluated in human liver microsomes. The 3HDZ pathway
      was the major route of metabolism representing 90% of total metabolism with a
      Vmax/Km ratio of 0.50-7.26 microliters min-1 mg-1 protein. 2. Inhibition of the
      two metabolic pathways of diazepam by omeprazole was investigated. The NDZ
      pathway was not affected by omeprazole whilst a Ki of 201 +/- 89 microM was
      obtained for the 3HDZ pathway (Km/Ki ratio of 3.0 +/- 0.9). 3. Inhibitory effects
      of omeprazole sulphone on the 3HDZ and NDZ pathways were also investigated.
      Omeprazole sulphone inhibited both pathways with similar Kis of 121 +/- 45 and
      188 +/- 73 microM respectively (Km/Ki ratios of 5.2 +/- 2.3 and 3.3 +/- 1.5
      respectively). 4. These in vitro data provide direct evidence for cytochrome P450
      inhibition as the mechanism for the well documented diazepam-omeprazole clinical
      interaction and indicate that omeprazole sulphone, as well as the parent drug,
      contribute to the inhibition effect.

PMID- 8864313
TI  - The influence of renal function on the pharmacokinetics of unchanged and acyl
      glucuroconjugated ketoprofen enantiomers after 50 and 100 mg racemic ketoprofen.
AB  - 1. To study the effect of renal dysfunction on the pharmacokinetics of ketoprofen
      (KT), and the possibility of saturation of clearance with elevation of dose,
      single 50 and 100 mg doses of racemic ketoprofen were administered in a cross
      over fashion to seven patients (creatinine clearance, CLCR, 6-72 ml min-1). 2.
      The stereospecific disposition kinetics of KT enantiomers and their acyl
      glucuronide conjugates (KTconj) were determined in plasma and urine for 24 h post
      dose. 3. Decreased renal function was associated with a reduced KT oral clearance
      (CLO) and terminal elimination rate constant (lambda z). Renal clearance of KT
      conj (CLrconj) was reduced with diminished renal function. 4. Following both 50
      and 100 mg doses, there was significant stereoselectivity in the AUC of KT (mean
      S/R, 0.87 and 0.83, respectively), the AUC of KTconj (mean S/R, 3.4 and 5.2,
      respectively) and the cumulative urinary excretion of KTconj (mean S/R, 2.1 and
      2.2, respectively). The stereoselectivity in renal dysfunction in contrast with
      the observations previously made in healthy subjects may suggest a disease
      related process. 5. CLO remained constant after increasing the dose, indicating
      linearity in the pharmacokinetics of KT despite reduced CLCR. CLrconj, however,
      was significantly reduced after the 100 mg dose suggestive of saturation of the
      urinary clearance and existence of a compensatory pathway. 6. Renal impairment
      reduces CLrconj and this appears to be the rate-limiting step for clearance of KT
      due to the observed stronger correlations of CLO with CLrconj than with CLCR. 7.
      Dose reduction of ketoprofen is indicated only for patients with CLCR < 20 ml min
      1.

PMID- 8864314
TI  - Pharmacodynamics and pharmacokinetics of BAY x 7195 aerosol, a new and selective
      receptor antagonist of cysteinyl-leukotrienes, in normal volunteers.
AB  - 1. The safety, tolerability and pharmacokinetics of BAY x 7195 aerosol, a new
      selective receptor antagonist of cysteinyl-leukotrienes, were investigated in
      healthy male volunteers in two observational studies (1 and 2 mg; n = 5 each) and
      two double blind, placebo-controlled two way crossover studies (4 and 8 mg; n = 6
      each) using the commercially available Inhaler Ingelheim M. 2. The
      pharmacodynamic effect was assessed by testing the ability of BAY x 7195 aerosol
      to inhibit leukotriene-D4 (LTD4) induced bronchoconstriction in healthy
      volunteers. Using a double-blind, placebo-controlled three way crossover design,
      volunteers received 2 and 4 mg of BAY x 7195 by means of a newly developed
      metered dose dry powder inhaler. Bronchoprovocation with nebulized LTD4 was
      performed 20 min and 8 h (n = 6 each) after drug administration. Specific airways
      of conductance (SGaw) served to assess the airway's response. 3. BAY x 7195
      aerosol was safe and well tolerated. Inhalation of the aerosol had no effect on
      baseline lung function. Only one volunteer reported cough following the
      inhalation of the 8 mg dose. 4. The pharmacokinetics of unchanged drug following
      the administration of BAY x 7195 aerosol were linear in the investigated range of
      doses and in general very similar to a previously investigated tablet
      formulation. Plasma-concentration vs time courses followed a two-compartment body
      model. Compared with oral administration of the tablet formulation absorption
      tended to be more rapid with the aerosol formulation. 5. Compared with placebo, 2
      and 4 mg BAY x 7195 increased the concentration of LTD4 needed to produce a 35%
      decrease in SGaw 20 min after drug administration by a mean (geometric) of 14.2
      and 29.7 fold, respectively. For both doses only three volunteers showed a
      protective effect against LTD4 induced bronchoconstriction 8 h after drug
      administration. Individual shifts in the concentration-response curve ranged
      between 0.4 and 7.2 fold. 6. In conclusion, the present results suggest that BAY
      x 7195 aerosol is a safe and potent but short acting receptor antagonist of
      cysteinyl leukotrienes in man.

PMID- 8864315
TI  - A study of 5 day fractionated ifosfamide pharmacokinetics in consecutive
      treatment cycles.
AB  - 1. Ifosfamide demonstrates increased clearance with time when administered daily
      for 5 days. The objectives of this study were to define whether the increased
      ifosfamide clearance was sustained between treatment cycles and whether it was
      reproducible in consecutive treatment cycles. 2. Seven patients with inoperable
      cancer received 1.5 g m-2 ifosfamide infused intravenously over 0.5 h, each day
      for 5 days, for two consecutive cycles. Urine and appropriately timed blood
      samples were collected for up to 24 h post ifosfamide infusion on day 1 and day
      5. Plasma ifosfamide concentrations were assayed by gas liquid chromatography and
      pharmacokinetic parameters were imputed using non-compartmental analysis. 3. The
      difference in the mean (n = 7) total ifosfamide plasma clearance between day 5
      and day 1 of Cycle I was an increase of 56.8 ml min-1 (99.8% CIs + 22.6-->+
      91.4). The difference in the mean (n = 7) total ifosfamide plasma clearance
      between day 1 of Cycle II and day 5 was a decrease of 61.9 ml min-1 (99.8% CIs 
      111.2 -->-12.6). The magnitude of the mean increase in total ifosfamide plasma
      clearance in Cycle II and Cycle I was similar because the difference between
      these means (0.9 ml min-1, 99.8% CIs -63.7-->+65.3) was not statistically
      significant. There was no change in the apparent volume of distribution of
      ifosfamide between the two study days in either of Cycle I or II, or between
      cycles. 4. The difference in the mean (n = 7) ifosfamide renal clearance between
      day 5 and day 1 of Cycle I was minus 0.4 ml min-1 (99.8% CIs -8.5-->+8.6); the
      means +/- s.d. wee 6.3 +/- 2.6 ml min-1 and 6.7 +/- 3.2 ml min-1 respectively.
      The difference in the mean (n = 4) ifosfamide renal clearance between day 5 and
      day 1 of Cycle II was -0.2 ml min-1 (99.8% CIs -5.7-->+5.2); the means +/- s.d.
      were 7.8 +/- 6.1 ml min-1 and 8.0 +/- 6.2 ml min-1 respectively. 5. These data
      suggest that the increase in total ifosfamide plasma clearance with time in a 5
      day fractionated regimen was due to an increase in ifosfamide metabolism which
      was not sustained over the 21 days between cycles, but was reproducible and of a
      similar magnitude in the two consecutive treatment cycles studied.

PMID- 8864316
TI  - Cholesterol lowering therapy inhibits the low-flow mediated vasoconstriction of
      the brachial artery in hypercholesterolaemic subjects.
AB  - 1. We tested whether lipid lowering treatment with HMG CoA reductase inhibitor
      modified the flow mediated large artery reactivity in primary pure
      hypercholesterolaemia. 2. Abnormalities in arterial reactivity have been
      described in the presence of high blood cholesterol, in particular an enhanced
      constriction of the brachial artery in response to acute induction of a low flow
      state. 3. Using pulsed-Doppler, we measured brachial artery diameter and flow
      velocity at rest and their changes induced by wrist occlusion before and after 3
      months of double-blind treatment by pravastatin (40 mg orally) in 13 subjects and
      placebo in 15 others. 4. The significant decrease (P < 0.01) in diameter induced
      by wrist occlusion before (0.34 +/- 0.08 mm) placebo and pravastatin (0.39 +/-
      0.10 mm) persisted after placebo (0.26 +/- 0.07 mm) but was abolished after
      pravastatin (0.07 +/- 0.05 mm). The absolute change in diameter induced by wrist
      occlusion was lower after than before pravastatin (P < 0.01) and lower after
      pravastin than after placebo (P < 0.05). Diameter during the wrist occlusion was
      higher after pravastatin than after placebo (4.35 +/- 0.16 vs 3.89 +/- 0.09 mm);
      P < 0.01). 5. These findings indicate that the lipid changes induced by
      pravastatin and/or some unknown but direct mechanism of the drug itself inhibit
      low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such
      effects may have important implications for the treatment of vasospasm often seen
      in the presence of high blood cholesterol.

PMID- 8864318
TI  - Pharmacokinetics of bismuth and ranitidine following single doses of ranitidine
      bismuth citrate.
AB  - 1. The pharmacokinetics of bismuth and ranitidine derived from ranitidine bismuth
      citrate given in single oral doses ranging from 200 mg to 1600 mg were evaluated
      in healthy subjects. 2. Bismuth was only minimally absorbed (< 0.5% of the amount
      dosed) after administration of ranitidine bismuth citrate, and peak plasma
      concentrations never exceeded 33 ng ml-1 in any subject. Plasma concentrations
      and urinary recoveries of bismuth at doses up to and including 800 mg were
      relatively constant and not proportional to dose. Bismuth absorption was
      increased more than proportionally with the dose at 1600 mg. 3. The
      pharmacokinetics of ranitidine after administration of ranitidine bismuth citrate
      were dose-proportional and consistent with previous observations for ranitidine
      administered alone. 4. Ranitidine bismuth citrate was well-tolerated in single
      oral doses of up to 1600 mg.

PMID- 8864317
TI  - Combination of methotrexate and sulphasalazine in patients with rheumatoid
      arthritis: pharmacokinetic analysis and relationship to clinical response.
AB  - 1. The influence of sulphasalazine (SASP) on the pharmacokinetics of low dose
      methotrexate (MTX) and the relation between pharmacokinetic variables and
      clinical response was studied in 15 patients with active rheumatoid arthritis
      despite > 6 months of SASP treatment. 2. SASP was stopped for 2 weeks. Thereafter
      a single oral dose of 7.5 mg MTX was administered after a standard breakfast.
      Blood was sampled initially every 30 min, thereafter hourly during 8 h. Urine was
      sampled every hour. Then 2000 mg SASP daily + 7.5 mg MTX weekly was given. After
      4 weeks the same procedure was repeated supplemented with concomitant
      administration of 1000 mg SASP. Clinical measurements included Ritchie articular
      index, number of swollen joints, ESR and the disease activity score.
      Pharmacokinetic analysis was performed using a two-compartment model with first
      order absorption and lag time. Results are given as mean (s.d.). Paired t-test or
      signed rank test were applied in the statistical analysis. 3. Pharmacokinetics of
      MTX without vs with SASP, means +/- s.d. were follows: AUC: 673 +/- 179 vs 628 +/
      210 (95% confidence interval [CI] of the difference was -71 to 159) ng ml-1,
      MRT: 5.2 +/- 1.3 vs 5.2 +/- 1.1 (95% CI -0.4 to 0.4) h, t1/2,z: 4.3 +/- 1.1 vs
      4.2 +/- 1.1 (95% CI -0.3 to 0.5) h, V/F: 59.3 +/- 29.3 vs 65.5 +/- 25.3 (95% 
      23.8 to 11.4) 1, CL/F: 12.3 +/- 5.0 vs 13.5 +/- 4.8 (95% CI -4.5 to 2.3) 1 h-1.
      CLR/F: 6.2 +/- 1.3 vs 6.3 +/- 2.1 (95% CI -1.3 to 1.1) l h-1. All P values were >
      or = 0.3. 4. A weak correlation existed between the change of ESR and the MRT,
      the t1/2,z and the V/F (Spearman correlation coefficients of 0.43, 0.50 and 0.50
      respectively, 0.05 < P < 0.1). 5. There is no significant influence of chronic
      SASP administration on the pharmacokinetics of MTX or vice versa. Of the clinical
      variables, only the ESR correlated consistently with some pharmacokinetic
      variables on MTX.

PMID- 8864319
TI  - Pharmacokinetics of bismuth and ranitidine following multiple doses of ranitidine
      bismuth citrate.
AB  - 1. The pharmacokinetics of bismuth and ranitidine derived from oral doses of
      ranitidine bismuth citrate 800 mg given twice daily for 28 days were examined in
      this double-blind, placebo-controlled, parallel-group study in 27 healthy
      subjects. 2. Bismuth accumulation in plasma reflected its multicompartmental
      disposition, achieving the majority of predicted steady state within 14-28 days.
      Bismuth absorption from ranitidine bismuth citrate is limited (< 0.5% of the
      dose), and bismuth elimination is predominantly renal secretion. Peak plasma
      concentrations did not exceed 19 ng ml-1, remaining well below those associated
      with bismuth toxicity. Bismuth was measurable at low concentrations in plasma and
      urine for up to 5 months after the last dose. Plasma bismuth concentration-time
      data and urinary excretion data were best described by separate
      multicompartmental models, with terminal half-lives averaging 21 days and 45
      days, respectively. 3. The pharmacokinetics of ranitidine derived from ranitidine
      bismuth citrate were similar to those of ranitidine administered alone.
      Ranitidine did not appreciably accumulate in plasma. 4. Ranitidine bismuth
      citrate was well-tolerated during 28 days of repeated dosing.

PMID- 8864320
TI  - A cohort study of the ocular safety of anti-ulcer drugs.
AB  - 1. Recently, some cases have been reported where intravenous use of omeprazole
      was followed by loss of vision. We followed up a cohort of close to 140,000
      persons during periods of treatment and non-treatment with five anti-ulcer drugs.
      2. The relative risk of vascular disorders of the eye during use of omeprazole
      compared with non-use was 1.8 (95% CI 0.5-6.0). Use of other anti-ulcer drugs was
      associated with a similar risk of vascular disorders. The relative risk
      associated with current use of any anti-ulcer drug was 1.9 (95% CI 1.1-3.4). We
      did not find a single case of optic inflammatory disorder during treatment with
      any of the five anti-ulcer drugs. 3. These results do not suggest a major
      increased risk for vascular or inflammatory disorders of the eye associated with
      use of omeprazole or other anti-ulcer drugs.

PMID- 8864321
TI  - (--)-Timolol is a more potent antagonist of the positive inotropic effects of (-
      )-adrenaline than of those of (--)-noradrenaline in human atrium.
AB  - 1. The affinity of (--)-timolol for beta 1- and beta 2-adrenoceptors was
      determined on isolated atrial preparations from patients undergoing open heart
      surgery. The times for onset and offset of antagonism of the positive inotropic
      effects of (--)-adrenaline and (--)-noradrenaline by (--)-timolol were measured.
      2. The antagonism of the positive inotropic effects of (--)-adrenaline and (--)
      noradrenaline by (--)-timolol (0.1-100 nM) was simple competitive in human atrium
      tissue. The slope of Schild-plots was not significantly different from 1.0 [0.93
      +/- 0.09 for (--)-adrenaline, 0.97 +/- 0.09 for (--)-noradrenaline]. 3. The
      inotropic effects of (--)-adrenaline were antagonized significantly more by each
      concentration of (--)-timolol than those of (--)-noradrenaline. KB-values (-log
      M) were 10.10 +/- 0.09 against (--)-adrenaline and 9.43 +/- 0.07 against (--)
      noradrenaline (P < 0.001). 4. Blocking kinetics of (--)-timolol for the beta
      adrenoceptor were relatively slow. Half-times for the onset of blockade by 10
      times KB of (--)-timolol were approximately 30 min for both (--)-adrenaline and (
      -)-noradrenaline; offset times were similar. 5. It is concluded that (--)-timolol
      has a higher affinity for the beta 2-adrenoceptor than for the beta 1
      adrenoceptor in human atrium. This property may be beneficial clinically in
      protecting against the beta 2-adrenoceptor hypersensitivity induced by cardiac
      beta 1-adrenoceptor blockade, but also explain why severe asthma can occur after
      administration of very low intra-ocular doses of the drug.

PMID- 8864322
TI  - The acute cardiovascular actions of intravenous thyrotrophin releasing hormone
      (TRH) in man are mediated by non-catecholaminergic mechanisms.
AB  - 1. Intravenous bolus doses of thyrotrophin releasing hormone (TRH, 50-1000
      micrograms) caused statistically significant, non-dose dependent and transient
      rises in blood pressure, heart rate and plasma catecholamines in healthy young
      males. 2. Mean peak incremental rises in systolic blood pressure (mean +/- s.e.
      mean) following 50, 200 and 500 micrograms TRH were 14.3 +/- 2.9 mmHg, 15.7 +/-
      3.2 mmHg and 17.1 +/- 3.9 mmHg respectively (all P < 0.05 vs placebo). Mean
      incremental rises in heart rate for the three doses of TRH were 8.2 +/- 2.2 beats
      min-1, 7.1 +/- 1.8 beats min-1, and 10.7 +/- 2.9 beats min-1 respectively (all P
      < 0.05 vs placebo). 3. Following the 50 micrograms and 1000 micrograms doses of
      TRH, plasma noradrenaline and adrenaline rose significantly (P < 0.05) between 4
      and 8 min. Mean +/- s.e. mean incremental plasma noradrenaline rise following 50,
      200 and 100 micrograms TRH were 0.4 +/- 0.13 nmol 1(-1), 0.37 +/- 0.21 nmol 1(-1)
      and 0.41 +/- 0.18 nmol 1(-1) respectively. Mean +/- s.e. mean incremental rise in
      adrenaline for the 50, 200 and 1000 micrograms dose were 0.13 +/- 0.04 nmol 1(-),
      0.08 +/- 0.03 nmol 1(-1), and 0.11 +/- 0.05 nmol 1(-1) respectively. 4. Following
      administration of the ganglion blocking drug pentolinium (5 mg) the incremental
      systolic blood pressure and heart rate rises following 500 micrograms TRH alone
      16.6 +/- 2.8 mmHg and 10.4 + 3.1 beats min-1 respectively. 5. The rises in plasma
      noradrenaline and adrenaline following TRH were attenuated by prior ganglion
      blockade. 6. alpha-Adrenoceptor blockade with thymoxamine (0.3 mg kg-1 bolus +
      0.3 mg kg-1 h-1 infusion), singly and combined with intravenous propranolol (10
      mg i.v. over 10 min), did not alter the pressor or tachycardic effects of 500
      micrograms TRH. 7. In conclusion, although plasma noradrenaline rises following
      i.v. TRH, suggesting activation of the sympathetic nervous system, this effect is
      not responsible for the pressor response to TRH, which appears to be due to
      either a direct vasoconstrictive effect on the peripheral resistance vessels or a
      direct inotropic/chronotropic effect on the heart.

PMID- 8864324
TI  - Effect of locally applied prazosin on the kinetics of the pupillary light reflex.
AB  - The effect of locally applied prazosin on pupillometric measures was studied in
      healthy volunteers, in an attempt to identify the role of alpha 1-adrenoceptors
      in the recovery time of the light reflex. Prazosin antagonized the mydriatic
      effect of phenylephrine, but did not alter that of tropicamide. Miotic responses
      to a range of light stimuli were measured under ambient temperature conditions of
      22 degrees C and 40 degrees C. The 40 degrees C condition was associated with
      shorter recovery times of the light reflex; prazosin increased the recovery time
      under both temperature conditions. Response amplitude was not affected by the
      temperature condition or prazosin. The results are consistent with the hypothesis
      that sympathetic neuromuscular transmission is involved in the redilatation of
      the pupil following a miotic response to light stimulation.

PMID- 8864323
TI  - Calcium supplementation and ototoxicity in patients receiving cisplatin.
AB  - We have studied the effect on ototoxicity of maintaining serum calcium
      concentration by calcium gluconate infusion in cancer patients receiving high
      dose cisplatin in a randomized study in two groups: 11 patients received calcium
      gluconate, 4 mg kg-1 i.v. infusion during cisplatin therapy; 11 other patients
      without any calcium supplementation served as controls. All of them received the
      first course of chemotherapy, based on cisplatin, 120 mg m2 with a hydration
      schedule. An audiogram was performed in each patient just before cisplatin and
      repeated after 1 day and 3 weeks. Mean total calcium concentration in control
      patients before and after chemotherapy was 2.2 +/- 0.14 (95% confidence interval
      1.9-2.5) and 2.0 +/- 0.13 (95% CI 1.7-2.24) mmol 1(-1) respectively (P = 0.0004)
      and for ionized calcium 1.22 +/- 0.52 (95% CI 0.21-2.23) and 1.11 +/- 0.07 (95%
      CI 0.97-1.25) mmol 1(-1) respectively (P = 0.0005). Serum magnesium levels were
      maintained or increased by magnesium supplementation. Although there was no
      change in serum total or ionized calcium, or serum magnesium in the calcium
      infusion group, no differences in hearing loss between the groups were observed.
      High-dose cisplatin chemotherapy for cancer patients induces an acute decrease of
      serum total calcium and serum ionized calcium and audiometric changes.
      Maintenance of calcium serum levels by calcium gluconate infusion did not protect
      against ototoxicity in those patients.

PMID- 8864325
TI  - The effects of reboxetine and amitriptyline, with and without alcohol on
      cognitive function and psychomotor performance.
AB  - Reboxetine is a novel antidepressant that has been shown to be effective in the
      treatment of major depressive disorders. The present experiment was designed to
      assess whether it affects the cognitive and psychomotor skills necessary for
      optimum function in everyday life. Ten healthy male volunteers received
      reboxetine 0.5 mg, 1 mg or 4 mg, amitriptyline 25 mg, or matched placebo with and
      without alcohol (0.6 mg kg-1) in a double-blind 10-way crossover study. A
      psychometric test battery was administered at baseline and at 1, 2.25, 3.5, 6 and
      9 h post-dose. The results showed that reboxetine had little or no effect on
      performance at any dose, compared with placebo. Amitriptyline, however, with and
      without alcohol, lowered critical flicker fusion threshold compared with placebo
      and/or reboxetine at all test points (e.g. at 3.5 h: 28.51 vs 30.33 Hz; P <
      0.05); increased reaction time (e.g. 619 vs 540 ms; P < 0.05); increased tracking
      error (e.g. 16.34 vs 8.54 RMS units; P < 0.05); and slowed short-term memory
      scanning (e.g. 742 vs 590 ms; P < 0.05). It is concluded that reboxetine at doses
      of 4 mg and below is free from disruptive effects on cognitive function and
      psychomotor performance, and that it does not act synergistically with alcohol,
      in contrast to amitriptyline.

PMID- 8864326
TI  - Clonidine and or adrenaline decrease lignocaine plasma peak concentration after
      epidural injection.
AB  - Clonidine is an alpha 2-adrenoceptor agonist increasingly used in combination
      with lignocaine for spinal or epidural anaesthesia because of a prolonged
      analgesic effect. Life adrenaline, it may decrease lignocaine peak concentration
      (Cmax), thus leading to decreased toxicity. However, the effects of clonidine on
      resorption of lignocaine into the systemic circulation from the epidural space
      remain to be established. We studied the pharmacokinetics of lignocaine after
      epidural injection of lignocaine with or without clonidine, adrenaline and both
      drugs. Total body clearance and apparent volume of distribution were similar in
      the four groups, but the maximum observed concentration (Cmax) was markedly
      increased in the plain solution group as compared with the other groups; (plain
      lignocaine: 7.15 +/- 2.04 micrograms ml-1, lignocaine + adrenaline: 3.11 +/- 136
      micrograms ml-1, lignocaine + clonidine: 4.48 +/- 1.26 micrograms ml-1,
      lignocaine + adrenaline + clonidine: 4.06 +/- 1.42 micrograms ml-1 [mean +/-
      s.d.]). Our results show that, clonidine decreases lignocaine Cmax to the same
      extent as adrenaline.

PMID- 8864327
TI  - Atovaquone has no effect on the pharmacokinetics of phenytoin in healthy male
      volunteers.
AB  - The potential pharmacokinetic interaction between atovaquone and phenytoin was
      investigated in 12 healthy male volunteers. Each volunteer received a single 600
      mg oral dose of phenytoin in the two treatment periods. On one occasion phenytoin
      was taken alone and on the other pre-treatment with 2000 mg atovaquone taken as
      two doses of 1000 mg as a microfluidized suspension. The mean (+/- s.d.) peak
      plasma concentrations (Cmax), apparent total clearance (CL/F) and terminal half
      life (t1/2) for phenytoin when administered alone were 10.6(1.8) mg 1(-1), 24.3
      (7.7) ml min-1 and 25(8) h, respectively. When administered together with
      atovaquone, phenytoin Cmax, CL/F and t1/2,z were 10.9 (2.0) mg 1(-1), 23.8 ml min
      1 and 24(6) h, respectively. There were no statistically significant differences
      in any of these plasma pharmacokinetic parameters. There were also no
      statistically significant differences in the fraction of circulating drug not
      bound to plasma protein or urinary excretion of 5-hydroxyphenyl-phenyl-hydantoin.
      In conclusion, there was no effect of atovaquone on the pharmacokinetics of
      phenytoin or its major metabolite after a single dose.

PMID- 8864328
TI  - Lack of pharmacokinetic interaction of pantoprazole with diazepam in man.
AB  - Pantoprazole, a substituted benzimidazole, is a potent and well tolerated
      inhibitor of the gastric H+,K(+)-ATPase with a low potential to inhibit
      cytochrome P450. In this randomized, placebo-controlled two-period crossover
      study, 12 healthy volunteers received placebo (reference) and 240 mg of
      pantoprazole (test) i.v. within 2 min once daily for 7 days each. On day 4 of
      either period, a 1 min bolus of diazepam (0.1 mg kg-1 body weight) was
      additionally injected. Pantoprazole was well tolerated and did not cause
      clinically relevant changes in heart rate, blood pressure, ECG and routine
      clinical laboratory parameters. There was no effect on diazepam clearance (0.021
      1 h-1 kg-1 for test and reference) and elimination half-life (36.8 for test, 40.4
      h for reference). Diazepam metabolism to desmethyldiazepam was not affected by
      pantoprazole. In conclusion, pantoprazole and diazepam may be administered
      concomitantly without dose adjustment even when high doses of pantoprazole are
      required.

PMID- 8864329
TI  - Patient awareness of the adverse effects of non-steroidal anti-inflammatory drugs
      (NSAIDs).
AB  - We set out to determine the extent to which two groups of patients reported
      having been informed about the adverse effects of NSAIDs. These consisted of 50
      patients who had suffered an acute gastrointestinal bleed while taking a NSAID,
      and 100 age, sex and drug matched controls who had not. Eight (16%) of the index
      patients, and 41 (41%) of the control patients remembered having been informed of
      potential adverse effects, an odds ratio of 3.65 (95% CI 1.55-8.58, P < 0.002).
      Two (4%) of the index patients recalled having been advised what to do should
      adverse symptoms develop, whereas 21 (21%) of the control patients did so, an
      odds ratio of 6.38 (95% CI 1.4-28.4, P < 0.01). Eighteen (36%) of patients who
      bled had experienced gastrointestinal pain prior to the bleed, but of these only
      two (11%) admitted reduced compliance with NSAID therapy. In contrast, 10 (67%)
      of the 15 control patients who had suffered epigastric discomfort admitted
      reduced compliance, an odds ratio of 16.0 (95% CI 2.6-98.8, P < 0.001). Our
      results suggest that patients who report not having been informed of adverse
      effects of NSAIDs are less likely to reduce intake in response to epigastric pain
      than patients who report having received such information. If the patients who
      bled had reduced their intake of NSAIDs to the same extent as apparently better
      informed control patients in response to epigastric pain, it is possible that
      some episodes of acute gastrointestinal bleeding would have been avoided.

PMID- 8864330
TI  - Lung bioavailability of chlorofluorocarbon free, dry powder and
      chlorofluorocarbon containing formulations of salbutamol.

PMID- 8864331
TI  - Delayed presentation of a mitral annular perforation complicating Staphylococcus
      aureus infective endocarditis.

PMID- 8864332
TI  - Atrial fibrillation in acute myocardial infarction: a prospective study based on
      data from a consecutive series of patients admitted to the coronary unit.

PMID- 8864333
TI  - The use of dobutamine stress echocardiography for the determination of myocardial
      viability.
AB  - Determining the presence of viable myocardium has prognostic and therapeutic
      implications in the treatment of ischemic heart disease. Dobutamine stress
      echocardiography (DSE) is one possible technique to help identify both
      hibernating and stunned but viable myocardium. Low-dose dobutamine infusion has
      an increased inotropic effect, while higher doses cause both inotropic and
      chronotropic effects. Thus, at lower doses cardiac augmentation occurs, and at
      higher doses regions of ischemia may be produced in the presence of significant
      coronary artery disease. This is manifested echocardiographically as changes in
      segmental wall motion. In theory, therefore, areas of viable myocardium should
      show improved wall motion at low doses, and areas of irreversible myocardial
      damage will remain akinetic. Five studies have investigated DSE for determining
      viability in the setting of acute myocardial infarction, thus looking for stunned
      but viable myocardium. DSE was shown to compare favorably with positron emission
      tomography and was highly sensitive and specific for predicting functional
      myocardial recovery. Five additional studies examined DSE for determining the
      presence of hibernating myocardium. The sensitivity and specificity of DSE were
      found to range from 71 to 92% and from 73 to 93%, respectively. The benefits of
      DSE include lower cost, convenience to both patient and physician, additional
      ancillary information, and determination of the possible need for urgent
      revascularization. Limitations of DSE include occasional technical difficulty in
      obtaining and interpreting studies and the need for larger volumes of viable
      myocardium to detect changes predictive of functional recovery. Larger trials are
      currently underway to confirm DSE as a reliable technique for determining
      myocardial viability.

PMID- 8864334
TI  - Factors limiting the enrollment of women in a randomized coronary artery disease
      trial. The Asymptomatic Cardiac Ischemia Pilot Study (ACIP) Investigators.
AB  - BACKGROUND AND HYPOTHESIS: Although it is recognized that women have been
      underrepresented in clinical trials of cardiovascular disease, the reasons for
      their limited enrollment have not been elucidated. METHODS: A prospective
      tracking system was established in the Asymptomatic Cardiac Ischemia Pilot study
      (ACIP) to monitor recruitment and identify protocol issues that interfered with
      the recruitment of women. Patients with stress test evidence for ischemia during
      the course of routine clinical care were screened for asymptomatic ischemia with
      an ambulatory electrocardiogram (ECG). RESULTS: Those with at least one episode
      of asymptomatic ischemia and angiographic evidence of coronary artery disease
      suited for revascularization could be randomized. Women comprised only 17% of the
      1,820 patients screened for asymptomatic ischemia, and only 14% of the 558
      patients randomized. The limited number of women screened for ischemia was
      largely due to the limited number of women (25% of all patients) found to have
      test evidence for ischemia or coronary artery disease suited for
      revascularization during the course of routine clinical care. Once patients were
      identified as having ischemia on stress test and ambulatory ECG, the major
      difference in eligibility was the difference in disqualifying angiograms,
      occurring 21/2 times as frequently in women as in men (p < 0.001). CONCLUSION:
      The percentage of women recruited was lower than the prevalence of ischemic heart
      disease in the general population because at participating centers (1) women were
      found to have ischemia less often than men during the course of routine clinical
      care, and (2) screening tests for ischemia were less predictive of protocol
      defined coronary disease in women than in men.

PMID- 8864336
TI  - Myocardial infarction in men aged 40 years or less: a prospective clinical
      angiographic study.
AB  - HYPOTHESIS: The study was undertaken to characterize acute myocardial infarction
      (AMI) in young patients. METHODS: In all 108 consecutive Mediterranean patients
      with AMI (102 men and 6 women), aged < or = 40 years, were prospectively included
      in this study over a period of 6.5 years. Coronary angiography was carried out
      within the first month and data from these patients with normal or diseased
      coronary arteries were compared. Clinical features, risk factors, and in-hospital
      and late morbidity and mortality were evaluated. RESULTS: Young patients with AMI
      represent 4.1% of the 2,644 patients admitted because of definite AMI during this
      period. The most common risk factors were cigarette smoking (94.5%) and
      hypercholesterolemia (48%). Location of the AMI was anterior in 37%, inferior in
      57.5%, and non-Q in 5.5%. A history of previous angina was present in 42.5% of
      the patients, including all seven patients with previous myocardial infarction
      (6.5%). However, in 52% of the patients the anginal episodes started in the week
      prior to the AMI. In-hospital mortality and mortality during a mean follow-up of
      41 +/- 23 months were 3.7 and 3.8%, respectively. The Kaplan-Meier actuarial
      curve assessed on 97 of 104 survivors was 100 and 94% at 1 and 5 years,
      respectively. Coronary arteries were angiographically normal in 17 (20%) of 87
      survivors. Compared with young patients who had obstructive lesions, this subset
      had a lower age and fewer risk factors, reinfarction (p < 0.05), and late angina
      (p < 0.01), but development of congestive heart failure and survival were similar
      in both groups. CONCLUSION: These data suggest that young patients with AMI are
      very frequently heavy smokers, have a high incidence of angiographically normal
      coronary arteries, and that the short- and long-term prognosis is excellent.

PMID- 8864335
TI  - Effects of heart rate on coronary circulation and external mechanical efficiency
      in elderly hypertensive patients with left ventricular hypertrophy.
AB  - BACKGROUND AND HYPOTHESIS: Mechanisms of heart failure in elderly hypertensive
      patients with hypertrophy have not been studied sufficiently. We hypothesized
      that impaired increment of coronary blood flow in response to increases in heart
      rate could be responsible for the occurrence or aggravation of heart failure.
      METHODS: To test this hypothesis, we measured coronary hemodynamics and lactate
      balance during basal conditions and atrial pacing in 21 elderly patients aged >
      or = 65 years (mean 74 +/- 6 years) without coronary arterial disease: 7
      normotensive control patients (Group 1), 7 hypertensive hypertrophic patients
      without a history of congestive heart failure (Group 2), and 7 patients with such
      history (Group 3). Coronary sinus blood flow (CSBF) was measured in coronary
      sinus using a thermodilution catheter. RESULTS: During basal conditions, heart
      rate did not differ among the three groups (67 +/- 3 in Group 1, 65 +/- 11 in
      Group 2, and 63 +/- 6 beats/ in Group 3). CSBF was significantly higher in the
      two hypertrophic groups than in the control group, but CSBF normalized by left
      ventricular mass was significantly lower in both hypertrophic groups. External
      mechanical efficiency (EME) obtained as left ventricular work divided by
      myocardial oxygen consumption did not differ among groups during basal conditions
      (36 +/- 9% in Group 1, 35 +/- 8% in Group 2, and 29 +/- 9% in Group 3, NS).
      During atrial pacing to increase heart rate by 25 +/- 5% (lower) and 54 +/- 6%
      (higher), the increases in CSBF were markedly limited in both hypertrophic
      groups, and the response in Group 3 was more depressed than that in Group 2. EME
      did not change in the control group or in Group 2, but did decrease to 21 +/- 5%
      in Group 3 during the higher pacing rate (p < 0.01 vs. basal conditions). In this
      group, the relationship between EME and heart rate showed a significant negative
      correlation (r = -0.56, p = 0.02). Lactate balance in coronary sinus blood showed
      a tendency to production in Group 3 during the higher pacing rate, suggesting
      myocardial ischemia. CONCLUSION: These findings suggest that in hypertensive
      hypertrophic patients with a history of heart failure, the coronary circulation
      system is vulnerable to increasing heart rate. In medical treatment of elderly
      hypertensive patients, control of heart rate in addition to blood pressure
      control should be considered to minimize the occurrence or aggravation of heart
      failure.

PMID- 8864337
TI  - Possible mechanisms of mitral regurgitation in dilated hearts: a study using
      transesophageal echocardiography.
AB  - HYPOTHESIS: This study was undertaken to clarify the mechanisms of mitral
      regurgitation (MR) in dilated hearts. METHODS: In all, 68 patients with dilated
      heart and MR, including 26 patients with dilated cardiomyopathy (DCM), 24 with
      prior anterior myocardial infarction (A-MI), and 18 with prior posteroinferior
      myocardial infarction (I-MI), as well as 25 normal subjects were examined by
      transesophageal two-dimensional and color Doppler echocardiography. RESULTS: The
      maximum area of the MR signal in the DCM group correlated positively with the
      anteroposterior diameter of the mitral annulus at late systole. Although the
      coaptation edge length of the anterior and posterior mitral leaflets appeared
      shorter in dilated hearts than in the hearts of controls, a significant
      difference did not exist. The length of the coaptation edge correlated negatively
      with the maximum area of the MR signal in all dilated hearts, and characteristic
      systolic displacement of the coaptation point of both mitral leaflets occurred.
      The MI groups demonstrated anterior and posterior displacement in the direction
      of the short axis of the left ventricle in the A-MI and I-MI groups,
      respectively. However, the DCM group demonstrated inferior displacement toward
      the long axis of the left ventricle; its magnitude correlated positively with the
      maximum area of the MR signal. CONCLUSION: A major cause of MR in dilated hearts
      is mitral malcoaptation due to displacement of the coaptation point of the mitral
      leaflets along the long or short axis of the left ventricle. This is caused by
      left ventricular enlargement and/or asynergy of the left ventricular wall, rather
      than by a decrease in mitral coaptation edge length due to mitral annular
      dilation.

PMID- 8864338
TI  - Relationship between late potentials and the predischarge electrocardiographic
      pattern in patients with acute anterior wall myocardial infarction.
AB  - HYPOTHESIS: The presence of late potentials on the signal-averaged
      electrocardiogram (SAECG) identifies patients at high risk for development of
      ventricular tachyarrhythmias after myocardial infarction (MI). METHODS: The
      electrocardiogram and left ventricular function in 65 patients recovering from a
      first acute anterior wall MI were analyzed. We compared the pattern of the ST
      segment (isoelectric or elevated) and of the T wave (positive or negative) with
      the SAECG using an orthogonal bipolar lead configuration (X, Y, Z) with
      bidirectional Butterworth filtering (Simson's method). RESULTS: Abnormal SAECG
      was found in 17 (26%) patients; 11 of 18 patients with ST elevation had abnormal
      SAECG, and only 6 of 47 patients with isoelectric ST segment developed abnormal
      SAECG (p < 0.0001, odds ratio = 10.74). Of 19 patients with positive T waves, 10
      had abnormal SAECG, and abnormal SAECG was found in 7 of 46 patients with
      negative T waves (p < 0.003, odds ratio = 5.27). When both parameters were
      considered together, 9 of 12 patients with ST elevation and positive T wave
      developed abnormal SAECG, and 35 of 40 patients with isoelectric ST and negative
      T wave had normal SAECG (p < 0.0002). Left ventricular ejection fraction was
      similar in patients with abnormal SAECG (43 +/- 14%) and normal SAECG (46 +/-
      11%). CONCLUSION: These findings suggest that patients with anterior wall MI and
      a predischarge pattern of ST elevation and positive T wave have a higher
      incidence of abnormal SAECG and therefore may have a worse prognosis, especially
      related to the subsequent development of ventricular arrhythmias.

PMID- 8864339
TI  - Cost-effective treatment of coronary artery disease--the new imperative.
AB  - Large lipid-lowering clinical trials have demonstrated a significant reduction in
      cardiovascular events and the need for cardiovascular procedures. These clinical
      and point trials used relatively weak treatment modalities, and when the cost
      savings of the reduced number of events is balanced against the estimated cost of
      treatment, the average difference is approximately $1,500 per patient per year.
      Arteriographic trials have used similar or more aggressive lipoprotein therapy
      over shorter periods of time. Estimates of cost savings from reduced clinical
      events balanced against the cost of treatment in these studies indicate a wide
      spectrum of estimated patient costs. These estimates range between a cost of
      $2,273 per patient per year to a cost savings of (-)$901 per patient per year.
      Extrapolation to the United States population with coronary artery disease (CAD)
      suggests that greater than one billion dollars per year could be saved if
      patients with CAD received similar treatment and responded in a similar manner.

PMID- 8864340
TI  - Nonatherosclerotic causes of coronary artery narrowing--Part III.
AB  - Approximately 5% of patients with acute myocardial infarction do not have
      atherosclerotic coronary artery disease but have other causes for their luminal
      narrowing. The third part of this three-part review of nonatherosclerotic causes
      of coronary narrowing focuses on coronary vasculitis, infectious diseases,
      Kawasaki's disease, metabolic disorders, metastatic disease, and substance abuse
      (cocaine).

PMID- 8864341
TI  - Directional coronary atherectomy for coronary artery spasm refractory to medical
      therapy.
AB  - A patient with severe medically refractory coronary artery spasm was treated
      successfully with coronary atherectomy of a mild (40%) left anterior descending
      artery stenosis. Before the procedure, the patient was dependent on intravenous
      nitroglycerin because of daily episodes of angina with ST-segment elevation
      despite receiving multiple combinations of antianginal therapies. Clinical
      response to coronary atherectomy was prompt and dramatic.

PMID- 8864342
TI  - Accelerated TPA for treatment of prosthetic valve thrombosis.
AB  - The first case of prosthetic valve thrombosis treated with an accelerated regimen
      of TPA is reported. The experience suggests that this therapeutic approach is
      feasible and may produce higher rates of patency for thrombosed prosthetic valves
      than other thrombolytic therapies currently available. This therapeutic strategy
      is worthy of further evaluation as a treatment for this disorder.

PMID- 8864343
TI  - Ventricular tachycardia initiated solely by reduced pacing rate during routine
      pacemaker follow-up.
AB  - Ventricular arrhythmias during a pacemaker follow-up have been previously
      reported, usually in conjunction with temporary asynchronous stimulation of a
      demand pacemaker through magnet application or by increased myocardial
      excitability, for example, following a myocardial infarction. The subject of this
      report, an 82-year-old pacemaker patient, had been VVI-paced without problems for
      the past 11 years. As an aid in determining the sensing threshold, the pacemaker
      lower rate was reduced from 70 to 40 beats/min. A ventricular tachycardia of 240
      beats/min was induced, most likely following short-long cycles; syncope resulted.
      To our knowledge, this is the first report of induction of a ventricular
      tachycardia during pacemaker follow-up solely by reduction of pacing rate and not
      by asynchronous pacing. This case demonstrates an additional potential risk
      associated with pacemaker rate manipulation during pacemaker follow-up.

PMID- 8864344
TI  - Aortic valve endocarditis in an acutely rejecting orthotopic heart transplant
      recipient.
AB  - Infective endocarditis is an infrequent but serious complication in heart
      transplant recipients. We report successful treatment for this serious
      complication.

PMID- 8864345
TI  - Sustained ventricular tachycardias associated with myotonic dystrophy.
AB  - Patients with myotonic dystrophy are reported to have a higher frequency of
      sudden death than the general population. Although causes of sudden death in
      myotonic dystrophy are suggested to be due to conduction of defects progressing,
      the HV interval cannot predict whether conduction system disease would develop or
      progress. We report two cases of myotonic dystrophy complicated with sustained
      monomorphic ventricular tachycardias (VT), which can cause sudden death. In Case
      No. 1, although the patient was treated successfully for sustained VT with
      verapamil in electrophysiologic studies, another sustained VT was confirmed 2
      years later. In Case No. 2, the patient showed decreased left ventricular
      ejection fraction and late potentials, and induced sustained VT that was
      identical to clinically documented VT. Although VT is believed to be rare in
      patients with myotonic dystrophy, these cases suggest that VT is a possible cause
      of sudden death.

PMID- 8864346
TI  - Antonio di Paolo Benivieni.

PMID- 8864347
TI  - Stress echocardiography for the assessment of myocardial ischemia and viability.

PMID- 8864348
TI  - The inauguration of Cytokine & Growth Factor Reviews.

PMID- 8864349
TI  - Ligand-induced dimerization of growth factor receptors: variations on the theme.
AB  - Growth, differentiation, apoptosis and movement of cells are regulated, in part,
      by polypeptide growth factors, or cytokines, which exert their effects by binding
      to cell surface receptors on the target cells. Recent observations have indicated
      that a common mechanism of activation of several classes of such receptors is
      ligand-induced dimerization or oligomerization of the receptors.

PMID- 8864351
TI  - MIF re-discovered: pituitary hormone and glucocorticoid-induced regulator of
      cytokine production.
AB  - The protein mediator known as macrophage migration inhibitory factor (MIF) was
      one of the first cytokine activities to be discovered and was described 30 years
      ago to be a T cell-derived factor that inhibited the random migration of
      macrophages. Despite the long-standing association of MIF with activated
      lymphocytes, the precise role of MIF in host responses remained undefined. Recent
      studies however, have led to the description of a pituitary mediator that appears
      to act as the natural, counter-regulatory hormone for glucocorticoid action
      within the immune system. Isolated as a product of an anterior pituitary cell
      line, this protein was sequenced and found to have the same structure as MIF. The
      major role of MIF appears to be to act at an inflammatory site or lymph node to
      counter-balance the inhibitory effects of steroids on the primary immune
      response, which must necessarily be mounted to eliminate the source of infection
      or tissue invasion.

PMID- 8864350
TI  - ISGF3 gamma p48, a specificity switch for interferon activated transcription
      factors.
AB  - Interferon (IFN) induces gene expression by phosphorylating latent transcription
      factors of the STAT family. Two different STAT multimeric complexes that bind
      distinct enhancer elements are activated by IFN alpha and IFN gamma, dictated by
      the DNA-binding protein ISGF3 gamma p48. This protein, a member of the IFN
      regulatory factor (IFR) family, acts as an adaptor protein to redirect STAT
      multimers from their intrinsic palindromic sequence specificity to interactions
      with a composite element composed of an IRF site juxtaposed with a STAT half
      site. Sequence similarity within the IRF family suggests that other members could
      serve as adaptor proteins for transcriptional activators. Recent evidence
      suggests that PIP (LSIRF) sequesters the Ets protein PU.1 at a composite DNA
      element lends support to this adaptor hypothesis.

PMID- 8864352
TI  - Interferon-gamma in autoimmunity.
AB  - Autoimmune disorders are characterized by abrogation of self-tolerance, resulting
      in emergence of activated self-reactive lymphocyte clones that trigger or
      maintain inflammatory reactions in specific organs. Interferon-gamma (IFN-gamma),
      as well as other cytokines, plays an important role as a regulator of the
      activation of self-reactive lymphocytes and of bystander and accessory cells that
      are involved in the autoimmune inflammatory response. In experimental models of
      autoimmunity, endogenous IFN-gamma has invariably been found to profoundly affect
      the disease course. However, it acts in one way in some diseases and in the
      opposite way in others.

PMID- 8864354
TI  - Chemokine receptors: structure, function and role in microbial pathogenesis.
AB  - The chemokine superfamily is composed of at least 20 different leukocyte
      chemoattractants that act by binding to a family of G protein-coupled receptors.
      Leukocyte subtypes respond preferentially to unique but overlapping subsets of
      chemokines as determined by the receptor distribution, yet the receptors appear
      to signal through a common Gi-type G protein. Since chemokines appear to play
      major roles in inflammatory pathology, their receptors may be good targets for
      developing leukocyte selective anti-inflammatory drugs. Two chemokine receptors,
      CC CKRS and ONCC, function pathologically as cell entry factors respectively for
      human immunodeficiency virus 1, the cause of AIDS, and Plasmodium vivax, the
      major cause of malaria.

PMID- 8864353
TI  - Chemokines in immune-mediated inflammation of the central nervous system.
AB  - Inflammatory cell recruitment to the central nervous system (CNS) is a cardinal
      feature of physiological and pathological processes, including multiple sclerosis
      (MS). Despite recent progress, the soluble signals that attract inflammatory
      cells from the vascular compartment into the CNS parenchyma remain obscure. We
      favor the hypothesis that chemoattractant cytokines termed 'chemokines' are
      uniquely important for mediating leukocyte entry into CNS tissues during immune
      mediated inflammation. Three lines of evidence supporting this hypothesis will be
      reviewed. The first regards expression of chemokines in animal models of immune
      mediated CNS inflammation and in the human disease, multiple sclerosis. The
      second line of evidence involves interventional studies of chemokine blockade in
      such model disorders. The third line of evidence comprises function of chemokines
      in the CNS, as analysed in transgenic mice. Investigation of CNS chemokine
      function will enhance our understanding of leukocyte recruitment to the CNS and
      suggest therapeutic strategies for neurological disorders.

PMID- 8864355
TI  - Up and down the growth hormone cascade.
AB  - In this review we present a personal overview of current research at different
      levels of the control cascade that regulates growth hormone and insulin-like
      growth factors, the primary endocrine regulators of post-natal growth and
      metabolism. Given the broad scope of this topic we have focused on only a few key
      areas of current interest.

PMID- 8864356
TI  - Cardiotrophin-1: a multifunctional cytokine that signals via LIF receptor-gp 130
      dependent pathways.
AB  - In a search for novel factors that induce cardiac myocyte hypertrophy,
      cardiotrophin-1 (CT-1) was identified by coupling expression cloning with an
      embryonic stem cell-based model of cardiogenesis. CT-1 is a new member of the IL
      6 family of cytokines that induce their biological effects through the shared
      signaling subunit, gp 130. The expression pattern of CT-1 and its range of
      activities in the hematopoietic, neuronal, and developmental assays suggest that
      CT-1 may play an important role in other organ systems, in addition to its
      actions in cardiac development and hypertrophy.

PMID- 8864357
TI  - Tumor suppressor activity of the TGF-beta pathway in human cancers.
AB  - The TGF-betas are a family of cytokines with antiproliferative activity on many
      cell types. Recent findings demonstrate that the TGF-beta receptor complex
      functions as a tumor suppressor gene in human malignancy. Somatic mutations of
      the type II subunit of the TGF-beta receptor (RII) have been demonstrated in
      several different tumor types. RII frameshift mutations within a short coding
      region polyadenine repeat are particularly characteristic of colon and gastric
      cancers that also demonstrate the phenotype of microsatellite instability (RER
      cancers). These and other mutations as in the type I receptor (RI) are associated
      with both loss of cell surface TGF beta receptors and with resistance of the
      cancer cells to TGF-beta-induced growth inhibition. Restoration of receptor
      expression by gene transfection reverses the transformed phenotype in cancer
      cells that lacked functional RII or RI. These receptors and, by implication, TGF
      beta as well as its complete signalling pathway, are thus new and novel additions
      to the family of human tumor suppressor genes.

PMID- 8864358
TI  - Cytokines in 1995.

PMID- 8864359
TI  - Interferons in 1995.

PMID- 8864360
TI  - Medial telangiectatic nevi: not always acral but sometimes sacral.

PMID- 8864361
TI  - Sacral medial telangiectatic vascular nevus: a study of 43 children.
AB  - BACKGROUND: Medial telangiectatic vascular nevi are capillary vascular
      malformations frequently observed at birth occurring mostly on the face or on the
      nape as a single lesion or as multiple macules affecting more than one site
      simultaneously. In 1990, Metzker and Shamir reported a medial telangiectatic
      vascular nevus (MTVN) in the sacral region along the midline and called this
      particular variety of MTVN 'butterfly-shaped mark'. OBJECTIVE: Our study was
      performed to investigate the morphology and localization of an MTVN in the sacral
      region (sMTVN) in a group of Caucasian children. METHODS: We observed 43 children
      with sMTVN, ranging in age from 1 month to 12 years (mean 8 years), for a period
      of 6 years. RESULTS: sMTVN was found as a red-violet macular lesion of rhomboid
      or triangular shape in 16 patients and as a group of little red-violet macules in
      10 patients. In 16 patients moreover the whole back was involved with many small
      red-violet spots on and around the spinal column, and in 1 patient with classic
      sMTVN satellite macules were also present over both buttocks. Four patients
      suffered from epilepsy with mental deficiency. In 6 patients, the family history
      showed sMTVN in one or more members of the family. No case presented an
      association with spina bifida. CONCLUSION: In our study, sMTVN shows a
      morphological polymorphism while Metzker and Shamir reported the same clinical
      aspect in all 25 of their patients. In accordance with these authors, we noted
      that sMTVN persist into childhood and adult life in the same way as occipital
      MTVN.

PMID- 8864362
TI  - Decreased bone mineral density in patients with pustulosis palmaris et plantaris.
AB  - BACKGROUND: Focal skeletal changes in patients with pustulosis palmaris et
      plantaris (PPP) are known to occur in a minority of patients. It is unknown
      whether these changes are unique events or whether they merely represent more
      progressed cases. OBJECTIVE: The study was undertaken in order to investigate
      possible diffuse bone changes in patients with PPP. METHODS: Bone mineral density
      (BMD) and biochemical markers of bone turnover were studied in 18 female patients
      and 18 age-matched controls. RESULTS: A significant correlation was found between
      lower-forearm BMD and disease duration (< 0.05). With increasing age, patients
      had significantly lower values than controls for both forearm and spine BMD (p <
      0.005); patients who had PPP for more than 2 years had significantly reduced
      forearm BMD (19.8%; 95% CI: 5.6-32.8%) and spine BMD (17.4%; 95% CI: 0.9-33.8%).
      No significant differences were observed in biochemical markers of bone turnover,
      physical activity or body mass index between patients and controls. The
      proportion of smokers among patients was four times higher than among controls (p
      < 0.0005). No significant dose effect was found between number of pack-years and
      BMD. CONCLUSION: Although we cannot exclude that prolonged use of topical
      steroids under occlusion is a confounding factor, the study suggests that PPP
      patients have decreased BMD due to primary pathogenic events, and that
      osteoporosis may be an additional problem for these patients.

PMID- 8864363
TI  - Detection of herpes simplex virus in exacerbated pemphigus vulgaris by polymerase
      chain reaction.
AB  - BACKGROUND: Herpes simplex virus infections are well known complications of
      various dermatoses and have also been reported in acantholytic diseases like
      pemphigus vulgaris or Darier's and Hailey-Hailey diseases. In pemphigus vulgaris,
      herpes simplex virus infection is considered to be rare and difficult to rule out
      clinically. OBJECTIVE: We report on 3 patients suffering from pemphigus vulgaris
      with exacerbation especially of lesions of the oral mucosa. METHODS AND RESULTS:
      While conventional techniques failed to unequivocally support a suspected
      herpetic infection, herpes simplex virus-specific DNA was detected by polymerase
      chain reaction (PCR) in cytological swabs taken from oral erosions of all 3
      patients. CONCLUSION: Herpetic infection should be considered in pemphigus
      vulgaris with lack of improvement under adequate immunosuppressive therapy. In
      addition, herpes simplex virus infection might to able to induce acute
      exacerbation of oral pemphigus. PCR can be useful for a highly sensitive and
      rapid molecular detection of herpes simplex virus.

PMID- 8864364
TI  - No alteration of biophysical parameters in the skin of subjects with respiratory
      atopy.
AB  - BACKGROUND: Skin hyperreactivity to environmental factors in patients with atopic
      dermatitis has been extensively studied. Conversely, little is known on the
      biophysical parameters of the skin in patients with respiratory allergy.
      OBJECTIVE AND METHODS: Functional characteristics of the skin in subjects with
      allergic asthma and/or rhinitis were studied using evaporimetry, capacitance and
      pHmetry. Data were compared to those of healthy subjects and patients with atopic
      dermatitis (AD). RESULTS AND CONCLUSIONS: Our results suggest that the skin of
      patients with atopic respiratory allergy does not show altered biophysical
      parameters when compared to normal skin, confirming that the functional
      alterations in AD skin are linked to the expression of the atopic diathesis in
      the skin.

PMID- 8864365
TI  - Hystrix-like keratosis with nail and joint-involvement: a new genodermatosis?
AB  - BACKGROUND AND OBJECTIVE: We describe a familial disorder featuring hystrix-like
      keratosis, thickened nails and plantar hyperkeratosis. The index patient, a 10
      year-old girl, suffered also from joint laxity and had long fingers, while in her
      mother only the typical skin lesions were observed. METHODS AND RESULTS:
      Histologic examination of the spiny hyperkeratoses in the index patient showed
      parakeratosis with marked cornoid lamella. On electron microscopy the
      keratinocytes exhibited intracellular vacuolization and aggregated tonofilaments,
      but no concentric shell formation. CONCLUSION: The striking skin lesions present
      in the 2 cases can be distinguished from other forms of hystrix-like
      hyperkeratoses such as nevus corniculatus or multiple digitate hyperkeratoses and
      hence may represent a new autosomal dominant genodermatosis.

PMID- 8864366
TI  - Dermatologic findings in HIV-1-infected patients: a prospective study with
      emphasis on CD4+ cell count.
AB  - BACKGROUND: Skin manifestations are common in patients infected with the human
      immunodeficiency virus (HIV) but the prognostic significance of may of them is
      not clear. METHODS: Skin disorders were studied in a cohort of 267 HIV-infected
      patients followed prospectively and were correlated to the CD4+ cell count.
      RESULTS: Among the most specific to HIV infection, Kaposi's sarcoma, oral hairy
      leukoplakia, molluscum contagiosum, xerosis and oral candidiasis were
      statistically associated to a low CD4+ cell count (200-300 CD4+/mm3; p < 0.001).
      Kaposi's sarcoma, oral candidiasis and molluscum contagiosum were more frequent
      in homosexual males (p < 0.05). Genital warts were more frequent in intravenous
      drug users (p < 0.001). CONCLUSIONS: These results suggest that dermatological
      findings are useful clinical predictors of the presence or progression of HIV
      infection.

PMID- 8864367
TI  - Silicone cream occlusive dressing--a novel noninvasive regimen in the treatment
      of keloid.
AB  - BACKGROUND: The use of silicone oil in the treatment of hypertrophic scars has
      recently been much discussed. Silicone gel and silicone cream containing 20%
      silicone oil have been demonstrated to effectively treat hypertrophic scars.
      However, the results in treating keloid are variable. OBJECTIVE: The purpose of
      this study was to evaluate the clinical efficacy of silicone cream with occlusive
      dressing in the treatment of keloid. METHODS: An open study was performed in 15
      Chinese patients with single or multiple keloids. Nineteen keloids were randomly
      selected and treated with silicone cream occlusive dressing (SCOD). The
      effectiveness was assessed using a scoring system involving elevation, redness,
      hardness, itching and tenderness or pain of the lesions. RESULTS: Fifteen out of
      19 keloids (79%) showed significant improvement after using SCOD for 6 months.
      None of the keloids progressed. CONCLUSIONS: We conclude that SCOD is easy to
      apply, noninvasive, painless, almost free of side effects. It is especially
      useful in children and those who cannot tolerate the pain or inconvenience of
      other treatment procedures. The action mechanism of SCOD is still unclear, though
      hydration and occlusion rather than silicone itself may play an important role.

PMID- 8864368
TI  - Efficacy of oral low-dose tretinoin (all-trans-retinoic acid) in lichen planus.
AB  - BACKGROUND: Retinoids were shown to be effective in the treatment of both oral
      and cutaneous forms of lichen planus. OBJECTIVE: Confirm the beneficial effect of
      low doses of oral tretinoin in lichen planus. METHODS: Eighteen patients with
      lichen planus were treated in an open study for up to 19 months. Efficacy and
      safety data were recorded. RESULTS: Complete remission was observed in 13 (72%)
      and marked improvement in 4 (22%) out of 18 patients. Six patients showed
      moderate and 12 had no side effects. CONCLUSION: Tretinoin is a valuable drug
      when given at low doses to patients with lichen planus who failed to respond to
      other therapies.

PMID- 8864369
TI  - Insulin-like growth factor axis, bone and collagen turnover in children with
      atopic dermatitis treated with topical glucocorticosteroids.
AB  - BACKGROUND: Topical glucocorticosteroids are widely used in the treatment of
      children with atopic dermatitis. Due to percutaneous absorption, these agents may
      become systemically available and cause inhibition of growth in children.
      However, the mechanisms responsible for the growth-suppressive effective are not
      fully understood. OBJECTIVE: To evaluate whether treatment with topical
      budesonide has any adverse effects on growth-hormone-dependent serum levels of
      insulin-like growth factor I (IGF-I) and insulin-like growth factor binding
      protein 3 (IGFBP-3), and on the serum markers of bone and collagen turnover
      osteocalcin, the carboxy-terminal propeptide of type I collagen (PICP), the
      carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP)
      and the amino-terminal propeptide of type III procollagen (PIIINP). METHODS: 13
      children (mean age 9.5 years) with atopic dermatitis were studied in an open
      longitudinal trial with run-in and budesonide treatment periods of 2 weeks'
      duration. During the run-in, only emollient was used. During the treatment
      period, budesonide cream 0.025% followed by emollient were applied twice daily
      all over the body except on the face. At day 14 of each period, blood samples
      were taken and eczema was scored according to a severity index based on extent
      and activity of the disease. RESULTS: Compared to the run-in, budesonide
      treatment was associated with a statistically significant reduction in mean
      severity index (p = 0.002). No statistically significant effects on serum levels
      of IGF-I, IGFBP-3, osteocalcin or ICTP were observed. The serum concentrations of
      PICP and PIIINP were reduced with (mean +/- 1 SD) 43 +/- 64 milligrams (95%
      confidence interval 3.5-80 milligrams, p = 0.03, t = 2.4, d.f. = 12) and 1.2 +/-
      1.5 milligrams (95% confidence interval 0.3-2.1 milligrams, p = 0.01, t = 3.0,
      d.f. = 12), respectively. CONCLUSION: Type I and III collagen turnover may be
      suppressed during short-term treatment with topical budesonide in children with
      atopic eczema. clinical implications need further study.

PMID- 8864370
TI  - Methotrexate-induced liver cirrhosis. Clinical, histological and serological
      studies--a further 10-year follow-up.
AB  - BACKGROUND: Methotrexate (MTX) may induce liver damage, which in some psoriatics
      will lead to fibrosis or cirrhosis. Studies performed 10 years ago on 25 patients
      with MTX-induced liver cirrhosis indicated that this type of cirrhosis was not of
      an aggressive nature. OBJECTIVE: The aim of this study was to evaluate the
      present status of surviving patients 10 years later, together with the latest
      clinical and histological data on patients who had died. METHODS: The
      investigations were carried out on 186 liver biopsies and 5 autopsies. All
      biopsies were studied by the same pathologist. Eleven surviving patients were
      also studied by analysis of serum aminoterminal propeptide of type III
      procollagen (PIIINP), which is an indicator of fibrogenesis, which is especially
      suitable for follow-up of fibrotic liver disease. RESULTS: Thirteen patients had
      died; 1 of these died of liver failure. Another patient died form an overdose due
      to misunderstanding of the prescribed dosage given elsewhere. The remaining
      deaths were non-MTX related, but all 5 autopsies showed some degree of cirrhosis.
      On the other hand, 13 patients had no histologically verified liver cirrhosis in
      their latest biopsy, and PIIINP was within the normal range in all 11 patients
      investigated, this in spite of total cumulative MTX doses from 1,120 to 18,645 mg
      (mean 7,171 mg). CONCLUSIONS: This study confirmed that in most patients MTX
      induced liver cirrhosis is not aggressive. However, continued low-dose MTX led,
      in spite of normal liver tests, 8 years after the last biopsy to liver failure
      and death in 1 of our patients. Our data support the continued use of liver
      biopsies in the surveillance of MTX-treated psoriatics.

PMID- 8864371
TI  - Matting of scalp hair.
AB  - Matting of the hair is a rare condition characterized by an irreversible tangling
      of scalp hair. This phenomenon has an uncertain etiopathogenesis, and it is
      assumed that physical, chemical and electrostatic factors may lead to its onset.
      In our case, vigorous brushing of the hair can be suggested as the etiological
      factor of matting.

PMID- 8864372
TI  - Tinea corporis bullosa anularis.
AB  - A case of annular bullous tinea corporis (tinea corporis bullosa anularis) in a
      27-year-old woman is reported. The infection was characterized by numerous
      lesions localized exclusively to the forearms and the legs. These lesions were
      erythematous and scaling with bullous and annular borders. Mycological culture
      yielded Microsporum canis.

PMID- 8864373
TI  - Ivermectin-responsive crusted scabies in HTLV1 carrier.
AB  - We report a case of HTLV1 infection revealed by crusted scabies and widespread
      dermatophytosis in an African woman. HTLV1 infection was not complicated by adult
      T cell leukemia or myelopathy. Crusted scabies is a marker of HTLV1 infection.
      The importance of oral ivermectin therapy in crusted scabies is emphasized.

PMID- 8864374
TI  - Localized lipoatrophia with persistent circulating autoantibodies and partial
      immunoglobulin A deficiency in a child.
AB  - A 7-year-old Caucasian girl developed lipoatrophic areas on the abdomen and left
      thigh. Laboratory tests showed a partial IgA deficiency, circulating
      autoantibodies (ANAs, double- and single-stranded anti-DNAs, rheumatoid factor).
      The clinical aspect resembles lipodystrophia centrifugalis abdominalis
      infantilis, but autoimmune abnormalities suggest connective tissue panniculitis
      which underlines the overlap between the different forms of localized
      lipoatrophias.

PMID- 8864375
TI  - Acrodermatitis continua of Hallopeau: response to combined treatment with
      acitretin and calcipotriol ointment.
AB  - Treatment of acrodermatitis continua of Hallopeau (ACH) is difficult and often
      disappointing. We describe a patient with an extensive ACH of all finger- and
      toetips, who was treated with acitretin combined with calcipotriol. A within
      subject left/right comparison was carried out between calcipotriol ointment (50
      micrograms/g) and the ointment base to investigate the additional value of
      calcipotriol above the ointment base. The side treated with calcipotriol as
      adjunct therapy showed an impressive improvement, well beyond the degree of
      improvement at the side treated with the ointment base only.

PMID- 8864376
TI  - Mycosis fungoides with marked hyperpigmentation.
AB  - Pigmentary changes in mycosis fungoides are not rare. Although poikiloderma and
      hypopigmented skin lesions have often been reported in the literature, there are
      few cases of mycosis fungoides presenting as a hyperpigmented skin lesion. We
      present a 57-year-old Japanese male with mycosis fungoides whose skin lesions
      showed marked hyperpigmentation. The skin lesion initially appeared as an
      irregularly shaped itchy annular erythema with central pigmentation predominantly
      on his extremities. During our 5-year follow-up, these skin lesions gradually
      increased in size and number. The erythema extended peripherally and became
      elevated with marked hyperpigmentation. Histology revealed extreme elongation of
      the rete ridges with infiltration of atypical large lymphoid cells characteristic
      of mycosis fungoides and numerous melanin granules in both the epidermal
      melanocytes and dermal melanophages. Although the exact mechanism of the marked
      hyperpigmentation is one of the unique characteristics in mycosis fungoides,
      especially in non-white individuals.

PMID- 8864377
TI  - Ocular sebaceous carcinoma. Two unusual cases, and their histochemical and
      immunohistochemical findings.
AB  - BACKGROUND: Since sebaceous carcinomas with a poor prognosis arising from the
      cutaneous adnexae of the eyelid are sometimes difficult to differentiate from
      squamous cell carcinoma or basal cell carcinoma on clinical and histopathological
      findings, definite differentiation between these tumors by additional methods is
      necessary. OBJECTIVE AND METHODS: To clarify the usefulness of histochemical and
      immunohistochemical examinations in diagnosing ocular sebaceous carcinoma,
      histochemical and immunohistochemical studies were carried out on the 2 patients
      with unusual ocular sebaceous carcinoma. RESULTS: The findings of ocular
      sebaceous carcinoma, at least in our 2 cases, were almost identical to those of
      extraocular sebaceous carcinoma. CONCLUSION: Immunohistochemical detection of
      human milk fat globules subclass 1, human milk fat globules subclass 2, and
      breast carcinoma-associated antigen 225 was useful for diagnosing ocular
      sebaceous carcinomas as well as extraocular ones.

PMID- 8864378
TI  - Congenital psoriasiform erythrokeratodermia with cleidocranial dysplasia,
      urogenital anomalies and atresia ani.
AB  - We describe two siblings with unique psoriasiform erythrokeratodermia associated
      with cleidocranial dysplasia, urogenital anomalies and atresia ani. The skin
      lesions were characterized by demarcated psoriasiform erythema with scaling. A
      skin biopsy revealed small abscesses containing polymorphonuclear leukocytes in
      the parakeratotic horny layer, elongation of the rete ridges and dermal papillae,
      and other findings consistent with psoriasis. A reverse-transcription polymerase
      chain reaction analysis disclosed increased expression of transforming growth
      factor alpha in the affected skin lesion of one of the siblings as well as in the
      skin of a patient with psoriasis. It is suggested that these cases are a variant
      of a congenital form of psoriasiform erythrokeratodermia.

PMID- 8864379
TI  - A case of diet-related pemphigus.
AB  - An experimental investigation has lately shown that certain allyl compounds of
      garlic are able to provoke acantholysis in normal human skin cultured in vitro.
      The acantholytic effect has been more prominent in the samples from DR4+ donor.
      We here report a case of superficial pemphigus which appeared spontaneously in a
      DR4,14+, 49-year-old man and which ran a course that proved to be affected by
      dietary factors, in particular by the consumption of garlic. In the absence of a
      conventional treatment and on a garlic-free diet only, the disease ceased for
      several months. Soon after an unintentional dietary test with a strongly and
      presumable garlic-spiced fish meal, the pemphigus recurred. Nutritional factors
      should be added to the ever-growing list of exogenous factors capable of inducing
      or perpetuating pemphigus in genetically predisposed individuals.

PMID- 8864380
TI  - Zosteriform lichen planus.
AB  - A 42-year-old woman developed a papular eruption mainly localized on the right
      side of the body and with a zosteriform pattern within the nerve segments TH6
      TH12, L1-L4 as well as S1 and S2. The skin lesions were characteristic of lichen
      ruber planus. The zosteriform arrangement of lichenoid papules is rare and is
      interpreted as a cutaneous reaction possibly triggered by some neural factor.

PMID- 8864381
TI  - Taxol-induced acral erythema.
AB  - Chemotherapy-induced acral erythema is a peculiar localized cutaneous response to
      several chemotherapeutic agents, mostly antimetabolites. Taxol is a recently
      developed antineoplastic drug that acts on the mitotic spindle and does not
      interfere with nucleic acid synthesis. We describe the first case of taxol
      induced acral erythema and report on additional data concerning the pathogenesis
      of this kind of toxic eruptions.

PMID- 8864382
TI  - Fibropapule multiplex of the nose: a variant of Cowden's disease?
AB  - A 58-year-old male presented multiple papules on the nose for over 10 years.
      Excisional biopsy revealed angiofibroma with perivascular fibrosis and coarse
      collagen fibers. Investigation for internal malignancies revealed gastric cancer.
      Messenger RNA for HER-2/neu and c-ras were found both in the lesions of the skin
      and stomach. We propose the term, fibropapule multiplex of the nose, which may be
      a variant of Cowden's disease associated with occult internal malignancy.

PMID- 8864383
TI  - Chloroquine: consideration of maximum daily dose (3.5 mg/kg ideal body weight)
      prevents retinopathy.

PMID- 8864384
TI  - A naturally occurring ring seborrheic keratosis.

PMID- 8864385
TI  - Chemotherapy-associated supravenous hyperpigmentation.

PMID- 8864386
TI  - 'Zosteriform' lichen planus: is it zosteriform?

PMID- 8864387
TI  - Langerhans cell histiocytosis over dilated skin vessels.

PMID- 8864388
TI  - Mechanical properties of skin in recombinant human growth factor abusers among
      adult bodybuilders.
AB  - A Cutometer was used to measure the mechanical properties of skin in 8 adult
      bodybuilders who were recombinant human growth hormone (hGH) abusers. Although
      skin deformability and biological elasticity remained within the normal range, an
      increase in dermal viscosity was noted. The expression of the activity of hGH or
      insulin-like growth factor I on target dermal cells is likely to be responsible
      for these findings.

PMID- 8864389
TI  - Lichen scrofulosorum type tuberculids of the face.
AB  - We report the case of a 27-year-old man who presents facial tuberculid of the
      type lichen scrofulosorum. This presentation stimulates interest in those aspects
      which cutaneous lesions associated with tuberculosis can manifest. As a
      consequence of the growing poverty and the flow of new immigrants into our
      industrialized regions, this pathology is becoming more frequent today.

PMID- 8864390
TI  - Clinical manifestations of cholesterol crystal embolism with subungual
      haemorrhages: a possible relationship?

PMID- 8864391
TI  - Dirofilariasis, a rare, usually imported dermatosis.
AB  - Dirofilariasis is an animal filariasis, exceptionally transmitted to man. The
      clinical manifestations are usually one or a few subcutaneous nodules which are
      frequently mistaken for lipomas or epidermic cysts. Inside the nodule may be
      found a worm, adult but immature. There are no systemic reactions and the only
      required treatment is surgical excision of the nodules.

PMID- 8864392
TI  - Netherton's syndrome: a severe neonatal disease. A case report.
AB  - A male infant was born with generalized erythroderma and scaling; the newborn
      demonstrated poor neonatal development and developed several complications such
      as hypernatremic dehydration, septicemia, gastroenteritis and seizures. In the
      neonatal period, the erythema faded, but exfoliation persisted. The parents are
      healthy but related. One older brother, who died at the age of 3 months, had
      shown the same clinical picture in the neonatal period and was diagnosed with
      congenital psoriasis. All clinical investigations, including serum
      immunoglobulins, complement levels and lymphocyte counts, were normal. Only
      raised total IgE and multiple positive specific IgE reactions were noted. Skin
      biopsy revealed an image of ichthyosis. Polarization microscopy of scalp hair
      showed trichorrhexis nodosa and discrete focal twisting of the hair shaft. This
      clinical picture and all histological findings are compatible with the
      indications of Netherton's syndrome. The purpose of this report is to call
      attention to this severe presentation of congenital ichthyosis in the neonatal
      period and to the difficulty of a correct diagnosis when confronted with
      congenital erythroderma.

PMID- 8864393
TI  - Late cutaneous syphilis and neurosyphilis.
AB  - We report two syphilitic cases of indeterminable duration. The dramatic cutaneous
      lesions of the female patient, compatible with secondary-tertiary syphilis
      associated with a positive VDRL reaction in CSF together with the criteria of
      neurosyphilis in her male companion (despite normal TPHA and IgG indices), led us
      to treat both of them in an optimal way. The clinical and serological evolution
      was favourable.

PMID- 8864394
TI  - Yellow nail syndrome and onychomycosis. Experience with itraconazole pulse
      therapy combined with vitamin E.
AB  - We describe the case of a female patient suffering from yellow nail syndrome
      (YNS) accompanied by bronchial hyperactivity and sinusitis. A dermatophyte
      onychomycosis was evident on some of her nails. Following treatment of the
      respiratory pathology and oral administration of vitamin E, there was an
      improvement in the nails. The improvement of the yellow nails was however more
      discernible subsequent to the introduction of itraconazole pulse therapy for
      secondary onychomycosis suggesting an effect of this treatment on ungual growth.

PMID- 8864395
TI  - Erythromelalgia: a clue to the diagnosis of polycythemia vera.
AB  - We report the case of a 74-year-old woman with recurrent episodes of symmetrical
      congestion and erythema in the distal lower legs causing a burning distress.
      Laboratory and clinical investigations revealed an underlying myeloproliferative
      disorder. The cutaneous symptoms were atypical of erythromelalgia. Salicylates
      and treatment of the underlying polycythemia were able to eliminate the skin
      lesions but not entirely suppress the subjective discomfort.

PMID- 8864396
TI  - Invasive atypical fibroxanthoma and eruptive actinic keratoses in a heart
      transplant patient.
AB  - We report a case of atypical fibroxanthoma (AFX) and eruptive actinic keratoses
      following heart transplantation in a 65-year-old patient. The AFX was diploid
      with moderate proliferative activity. It recurred and proved to invade the large
      vessels of these tumors during immunosuppressive therapy highlights the
      cumulative intervention of ultraviolet light and immune dysregulation in the
      development of some skin cancers in transplant patients.

PMID- 8864397
TI  - Primary systemic amyloidosis. A report of 2 cases.
AB  - We report 2 cases of primary systemic amyloidosis. A monoclonal gammopathy was
      confirmed at the postmortem examination of the first patient. An extensive search
      for evidence of chronic infection, inflammation, neoplasms and paraproteinemia
      was conclusively negative in the other patient. The recognition of cutaneous
      signs of primary systemic amyloidosis is crucial to insure a rapid management
      aimed at postponing the fatal issue of the disease.

PMID- 8864398
TI  - Keratosis lichenoides chronica: an unusual case.
AB  - An unusual severe case of keratosis lichenoides chronica is presented. In
      addition to the typical lichenoid reticulated lesions, the patient had a
      prominent erythematosquamous involvement of the face and lips. Sclerodactylia was
      present and represented a yet undescribed manifestation of the disease.

PMID- 8864399
TI  - Epidermolysis bullosa dystrophica of Hallopeau-Siemens and squamous-cell
      carcinoma: a case report.
AB  - A 46-year-old patient suffering from Hallopeau-Siemens type epidermolysis bullosa
      dystrophica presented a large squamous-cell carcinoma of the left hand. No
      metastases were observed. The tumour was resected and the phalanxes were
      amputated. The wound was covered with autologous skin grafts. Squamous-cell
      carcinoma is extremely aggressive in these patients and surgery is the only
      effective therapy. This life-threatening complication should always be kept in
      mind and a biopsy taken of every chronic, non-healing ulceration and of each
      atypical lesion.

PMID- 8864400
TI  - Cotinine concentrations in plasma of smoking pregnant women and their infants.
AB  - In the Netherlands 30% of all women of reproductive age are habitual smokers. One
      third of these women continue to smoke during pregnancy. Tobacco smoke consists
      of more than 3600 different compounds. One of its chief pharmacologically active
      ingredients is nicotine of which 60% is metabolized to cotinine. Cotinine is the
      best available biochemical marker of nicotine consumption because it is specific
      for tobacco smoke exposure and it has a relatively long mean t1/2 of 15 hours. In
      the present study nicotine and cotinine concentrations were measured in 25
      smoking and 25 non-smoking healthy pregnant women. In all 25 non-smoking pregnant
      women nicotine and cotinine levels were < 10 mg/l. Light smokers (< 10
      cigarettes/day) were found to have nicotine blood concentrations < 10 mg/l and
      cotinine levels varying between 40 and 99 mg/l. Heavy smokers (> or = 10
      cigarettes/day) had nicotine concentrations < 10 mg/l, but high cotinine levels
      varying from 115 to 199 mg/l. Cotinine was also determined in 25 neonates of non
      smoking mothers and in 34 neonates of smoking mothers. In 9 of these 34 newborns
      the relationship between maternal and neonatal cotinine concentrations was
      investigated. Cotinine levels in neonates born to non-smokers and to women who
      smoked less than 10 cigarettes/day were below the detection limit of 10 mg/l.
      Cotinine values in neonates whose mothers smoked > or = 10 cigarettes/day were
      significantly higher than in those whose mothers smoked < 10 cigarettes/day, but
      significantly lower than in their mothers. The results of this study confirm that
      cotinine is more useful than nicotine in discriminating non-smokers, light and
      heavy smokers. Cotinine concentrations were significantly lower in the neonates
      than in their mothers, but there was a strong positive linear relationship
      between maternal and neonatal cotinine concentrations.

PMID- 8864402
TI  - Capillary electrophoresis of serum proteins. Reproducibility, comparison with
      agarose gel electrophoresis and a review of the literature.
AB  - Conditions of serum protein analysis by capillary electrophoresis were optimized
      and within day, between day and between capillary variations were examined for
      both migration times and relative peak areas. For the five currently accepted
      zones, albumin, alpha 1, alpha 2, beta and gamma-globulin, reproducibilities of
      migration times were in the range of 2.3-3.1% (n = 200 measurements). Although
      variations in relative peak areas were slightly higher than those obtained by
      conventional agarose gel electrophoresis, from a resolution perspective,
      capillary electropherograms provided better detail than the densitometric scans
      of agarose gel electrophoresis. Precise localization of C3 and transferrin in
      capillary electrophoresis resulted in more accurate detection of the beta
      globulin fraction. When C3 appeared in the gamma-fraction it was not detected as
      a separate peak in agarose gel electrophoresis, whereas it was in capillary
      electrophoresis. In artificially prepared mixtures of highly purified albumin and
      gamma-globulin preparations, best correspondence with theoretical values was
      found with capillary electrophoresis. Inter-individual variations and reference
      values were obtained by measuring 140 samples from healthy controls (59 females,
      81 males) with both techniques. For capillary electrophoresis the inter
      individual variations of the albumin, alpha 1, alpha 2, beta and gamma fractions
      were respectively 6, 21, 19, 14 and 18% and for agarose gel electrophoresis 5,
      20, 17, 18 and 22%. From these results it can be concluded that the more precise
      localization of the beta- and gamma-globulin fraction results in about 4% lower
      inter-individual variations in capillary electrophoresis compared to agarose gel
      electrophoresis. For the other fractions, comparable variations were obtained.
      Differences between males and females were not significant. For patient samples,
      a good correlation was found between capillary electrophoresis and agarose gel
      electrophoresis data for all five protein fractions. We conclude that separation
      efficiency of capillary electrophoresis is better than that of agarose gel
      electrophoresis and even weak monoclonal components can easily be distinguished
      with the capillary electropherogram. Capillary electrophoresis is a qualitatively
      good, cheap, fast and easy to perform alternative to agarose gel electrophoresis.

PMID- 8864401
TI  - Ornithine decarboxylase levels in patients with normal colonic mucosa.
AB  - We describe a systematic examination of ornithine decarboxylase activity in 120
      colonic mucosal samples which were obtained from 20 subjects without colonic
      disease to establish the normal mean and standard deviation from proximal to
      distal colon. Ornithine decarboxylase activity was determined by releasing CO2
      from DL-[1-14C]ornithine. The mean ornithine decarboxylase levels (CO2 liberated)
      ranged from 0.26 +/- 0.08 nmol/h.mg protein in the caecum to 0.44 +/- 0.16
      nmol/h.mg protein in the rectum. There was no difference between sex and age.
      Ornithine decarboxylase was not stimulated by guanosine 5'-triphosphate. alpha
      Difluoromethylornithine showed an ornithine decarboxylase inhibition of 97.1%.
      Ornithine decarboxylase activity can be measured with reliable precision and
      reproducibility. The knowledge of the normal range of ornithine decarboxylase
      activity in normal human colonic mucosa is necessary for the determination of
      ornithine decarboxylase activity in pathological findings, especially in
      malignant transformation.

PMID- 8864403
TI  - Development and evaluation of an ELISA method for the determination of
      lipoprotein lipase mass concentration--comparison with a commercial, one-step
      enzyme immunoassay.
AB  - We developed a non-competitive, enzyme-linked, immunosorbent assay (ELISA) for
      the quantitation of lipoprotein lipase (LPL) in human postheparin plasma using
      affinity-purified antihuman milk lipoprotein lipase antibodies produced in
      chicken eggs and a monoclonal antibody directed against human lipoprotein lipase.
      We compared our ELISA method with a commercially available sandwich-enzyme
      immunoassay (Markit-F LPL EIA Kit, Dainippon Pharmaceutical Co, Ltd. Osaka,
      Japan). The reference values for lipoprotein lipase catalytic activity
      concentration and mass concentration in healthy Finns were determined.
      Lipoprotein lipase activity concentration (mean +/- SD) was 297 +/- 112 U/l in
      women, and mass concentration as measured by the ELISA method was 1058 +/- 367
      micrograms/l. The corresponding values for men were 247 +/- 97 U/l and 815 +/-
      207 micrograms/l, respectively. Across the whole concentration range of the ELISA
      method, the control samples' intra- and inter-assay coefficients of variation
      (CV) were 5.1% and 6.5%, respectively. The correlation between the ELISA and EIA
      methods was good, r = +0.81. The importance of the correct standardisation of
      immunoassays is discussed.

PMID- 8864404
TI  - Cathepsin D serum mass concentrations in patients with hepatocellular carcinoma
      and/or liver cirrhosis.
AB  - Cathepsin D serum mass concentrations were determined by enzyme immunoassay in
      patients with hepatocellular carcinoma (n = 51) and/or liver cirrhosis (n = 92)
      or benign steatosis (n = 16) and correlated with some biochemical and clinical
      properties of these diseases. Increased cathepsin D serum mass concentrations (P
      < 0.001) were observed in all these groups of patients as compared to normal
      subjects (n = 98). However, patients with steatosis had serum mass concentrations
      of this enzyme significantly lower (mean 2-3 fold) than those measured in cancer
      patients (P < 0.05) or cirrhotic patients (P < 0.001). Interestingly,
      significantly higher cathepsin D serum mass concentrations (mean + 62%) (P <
      0.006) were determined in the cirrhosis group as compared to cancer patients. No
      correlation between cathepsin D and a number of clinical and biochemical
      properties examined, namely, alpha-foetoprotein, number of neoplastic lesions and
      tumour size in cancer patients or, Child-Pugh grade of severity of cirrhosis and
      other enzymes of liver function tests in the cirrhotic group was found. The
      present data and those from other studies which indicate that cathepsin D may be
      involved in carcinogenesis suggest that this enzyme may be potentially useful as
      an additional biochemical marker to identify cirrhotic patients who may develop
      precancerous hepatic nodules.

PMID- 8864405
TI  - Faecal nitrogen determination by near-infrared spectroscopy.
AB  - The well-known Kjeldahl method for the determination of faecal nitrogen is rather
      complex, time-consuming and expensive. Therefore, the use of near-infrared
      spectroscopy in determining the amount of nitrogen in faeces has been studied. To
      our knowledge we are the first to present the calibration equation for the
      determination of nitrogen with near-infrared spectroscopy. A good correlation (r
      = 0.96) was found between results from near-infrared spectroscopy and the
      Kjeldahl method. The imprecision of both methods was comparable. Once the rather
      laborious calibration has been performed, near-infrared spectroscopy is shown to
      be a very simple and rapid method for measuring nitrogen in faeces.

PMID- 8864406
TI  - Population-based differences in thyrotropin and thyroxine distributions in
      healthy newborns revealing results from independent reagent evaluation.
AB  - An independent evaluation of reagents for the determination of thyroxine and
      thyrotropin from dried blood spot samples taken from newborns between the third
      and fifth day of life revealed striking differences in the thyrotropin
      distribution among newborns from Byelorussia. An analysis of the thyrotropin
      distribution from Byelorussian newborns showed that 40% of samples had over 5
      mIU/l blood. In other European populations comparable in respect to timing of
      blood collection, this fraction varied from only 1% (Stockholm, Sweden) to 3.7%
      (Lille, France). The reason for the "shift right" in Byelorussian newborns
      remains to be further investigated. This shift can be attributed to the
      synergetic effects of mild-moderate iodine deficiency and/or as yet unidentified
      environmental factors. The differences observed in cumulative distribution
      patterns obtained by two commercial methods question the use of absolute figures
      (such as the proportion of samples over 5 mIU/l) for the purpose of inter
      population comparisons.

PMID- 8864407
TI  - Evaluation of an automated pyrogallol red-molybdate method for the measurement of
      urinary protein in rats.
AB  - Methods for quantitating urinary protein differ in their ranges of linearity,
      technical ease of performance, and applicability to automated analyzers. The
      Coomassie Brilliant Blue method is widely used but has limited linearity and its
      tendency to stain glassware has limited its application to automated analyzers.
      We evaluated a pyrogallol red-molybdate protein dye-binding method (Biotrol USA,
      Inc.) on a Hitachi 705 analyzer for the quantitation of urinary protein in rats.
      This method showed a wide range of linearity (up to 2.6 g/l) and good precision.
      Within-run CVs of 6.6% and 1.3% and between-day CVs of 10.9% and 1.1% were
      observed at mean protein concentrations of 0.16 g/l and 1.96 g/l, respectively.
      In addition, rat urine protein results from this method correlated well (r2 =
      0.998, n = 40) with a Coomassie Brilliant Blue method (QuanTtest Blue,
      Quantimetrix Corporation). No significant or unexpected interferences were
      encountered with this method. We conclude that the automated pyrogallol red
      molybdate method is an acceptable and practical alternative to the Coomassie
      Brilliant Blue method for the quantitation of urine protein in rats.

PMID- 8864408
TI  - High dose hook effect and sample carryover in carcinoembryonic antigen assay
      performed on the Boehringer-Mannheim ES-300 automated immunoassay system.

PMID- 8864409
TI  - Profilin: an update.

PMID- 8864410
TI  - Clinical evaluation of a new quantitative method for specific IgE antibodies.
AB  - We studied the analytical and clinical efficiency of a "second generation"
      technique for the in vitro determination of specific IgE, the so-called CARLA
      system (Capture Assay Radim Liquid Allergen). Reproducibility studies
      demonstrated satisfactory intra- and inter-assay analytical imprecision. The
      linearity test gave good results, and no significant interference by non-specific
      total IgE was found. The diagnostic efficiency of the system for the five most
      representative aeroallergens (D1, Dermatophagoides pteronyssinus; E1, Cat's
      epithelium; G5, Lolium perenne; W19, Parietaria officinalis and W5, Arthemisia
      absinthium) was evaluated using the Receiver Operating Characteristic (ROC)
      analysis in eighty-nine patients with suspected inhalant allergies. For each
      aeroallergen the area under the ROC curve and the most efficient threshold were
      calculated. Satisfactory areas under the ROC curve were found for D1, G5, E1 and
      W19, while a lower diagnostic efficiency was observed for W5. The most efficient
      thresholds differed from one allergen to another, although the differences were
      not great.

PMID- 8864411
TI  - Statistical analysis of heterogeneous pharmacokinetic data from the literature.
AB  - To obtain the reliable pharmacokinetic quantities necessary for the adjustment of
      individual drug dosages, the pharmacokinetic data in the literature must be
      analysed by various appropriate statistical methods. Generally, pharmacokinetic
      quantities have been calculated from small sample sizes and published in
      different ways (the coefficient of variation of an estimated pharmacokinetic
      quantity is often higher than 40 percent). In the present study data were
      therefore structured and clustered according to the important influence
      variables. The important influence variables were obtained by known multivariate
      statistical methods. To obtain optimal estimators (uniformly minimum variance
      unbiased estimators) for the quantities inside the clusters, goodness of fit
      tests must be performed. Skewed distributions and samples with heterogeneous
      variances must be subjected to transformation procedures to obtain normally
      distributed values with homogeneous variances. The population-derived estimate of
      the a priori knowledge of pharmacokinetic quantities can be obtained by a
      statistical algorithm proposed in this paper. Information on the quantities half
      life, total body clearance and volume of distribution of vancomycin were
      extracted from over 200 publications. These data were analysed with the proposed
      statistical algorithm, yielding population-based estimates for half-life,
      clearance and volume of vancomycin, taking into consideration the detected
      influence variables--renal function and the age of the patient. Important
      dependencies between different variables are discussed.

PMID- 8864412
TI  - Multicentre evaluation of an immunological rapid test for the detection of
      troponin T in whole blood samples.
AB  - In a multicentre study we assessed the analytical and diagnostic performance of a
      rapid test (TROPT rapid test, Boehringer Mannheim; in the USA: CARDIACT) for
      cardiac troponin T compared to quantitative troponin T ELISA and creatine kinase
      MB mass determinations. The rapid test requires 150 microliters of heparinized or
      EDTA whole blood; serum is not suitable. Interference testing with biotin,
      haemoglobin and 27 standard drugs yielded no significant influence in the
      physiological range. Skeletal muscle troponin T concentrations > or = 40
      micrograms/l gave positive results with the rapid test. We used the rapid test
      for 369 samples from 203 patients with suspected acute coronary syndromes and
      compared the results to troponin T ELISA and creatine kinase-MB mass. 90 patients
      (44%) were primarily classified as having myocardial infarction by the WHO
      criteria. Twenty-two (20%) of the 113 non-myocardial infarction patients were
      unstable angina pectoris cases showing increased troponin T ELISA but not
      increased creatine kinase-MB mass values. Consequently, these were classified as
      minor myocardial damage cases. The rapid test was positive in 99% of all samples
      with a troponin T ELISA value > or = 0.30 micrograms/l and negative in 95 to 96%
      of all samples below this value. Diagnostic sensitivities for the detection of
      acute myocardial infarction within the first 12 hours after onset of pain were
      the same, 90%, for the rapid test, troponin T ELISA and creatine kinase-MB mass.
      After 48 hours, diagnostic sensitivity of creatine kinase-MB mass sharply
      decreased whereas that of the troponin T assays remained close to 100% beyond 72
      hours after onset of symptoms. Diagnostic specificities for acute myocardial
      infarction (WHO) of all markers remained between 80 and 100% over this time. The
      diagnostic sensitivity of the rapid test for the detection of high risk unstable
      angina pectoris patients with minor myocardial damage was nearly the same as for
      troponin T ELISA. A major advantage of the rapid test is the ease of use and 20
      minute turn around time. This facilitates the detection of increased troponin T
      at alternate sites.

PMID- 8864413
TI  - Growth hormone, insulin-like growth factors and bone remodelling.

PMID- 8864414
TI  - The pathogenesis of vascular complications of diabetes mellitus: one voice or
      many?

PMID- 8864415
TI  - Prostacyclin (PGI2): a potential mediator of c-fos expression induced by
      hydrostatic pressure in osteoblastic cells.
AB  - Application of compressive forces to osteoblastic cells is known to cause
      specific cellular responses. We report that hydrostatic pressure increased c-fos
      mRNA expression in MC3T3-E1 cells after 15, 30 and 60 min. This effect was absent
      when 5 x 10(-7) mol L-1 indomethacin, an inhibitor of prostaglandin synthesis,
      was present in the culture medium during pressurization. Using radioimmunoassay,
      a significant increase in the concentrations of 6-keto-PGF1 alpha, the stable
      conversion product of prostacyclin (PGI2), in the conditioned medium of
      pressurized cells, was measured after 60 min. In contrast, PGE2 levels were not
      significantly changed and we therefore assume that under these experimental
      conditions PGE2 is not responsible for the transduction of the hydrostatic force.
      However, we also found that PGE2 has the capacity to induce c-fos mRNA in MC3T3
      E1 cells. Furthermore, we show for the first time that the stable prostacyclin
      analogue, Iloprost-Trometamol (Ilomedin), is a potent activator of c-fos gene
      transcription. Our data suggest that prostacyclin is a likely candidate in
      mediating the effect of hydrostatic compressive stress on bone cells by
      regulating the level of c-fos mRNA, a member of the activator protein (AP-1)
      complex and potent regulator of osteoblastic proliferation and differentiation.

PMID- 8864416
TI  - Cyclosporine induces high bone turnover and may contribute to bone loss after
      heart transplantation.
AB  - Cardiac transplantation has become a successful therapy for end-stage heart
      disease. However, increased bone loss has been observed in heart transplant
      recipients, sometimes being responsible for osteoporotic fractures.
      Glucocorticoids cause dose-related bone loss, particularly in the first 6-12
      months of use, but cyclosporine might play a role as well. The evolution of bone
      mineral density (BMD) and biochemical parameters was prospectively assessed in 24
      patients (mean age 52 years) from cardiac transplantation. All patients received
      cyclosporin A (CsA) and prednisone, the latter at decreasing dosage. The mean
      current daily dose of CsA was 321 mg and serum levels of CsA were constant. All
      patients received calcium (500 mg day-1) and vitamin D (1000 U day-1) for
      prevention of bone loss. BMD (gcm-2) was measured in 17 patients at the lumbar
      spine, femoral neck and total hip with dual energy X-ray absorptiometry every 6
      months. Spinal BMD as well as neck and total hip BMD decreased at 6 and 12 months
      after transplantation, being statistically significant at the three sites: -5.6
      and -3.4% for the lumbar spine, -9.3 and -8.5% for the femoral neck, -4.8% and 
      6.0% for the total hip respectively. Parathyroid hormone (PTH) and osteocalcin
      (BGP) increased by 90% and 800% respectively between pretransplantation values
      and 18 months after transplantation. BGP levels measured every 2 months from
      transplantation increased continuously from 8.7 micrograms L-1 (mean +/- SEM)
      before transplantation to 31.3 +/- 10.1 (P < 0.05) at 4 months, to 59.1 +/- 8.8
      (P < 0.01) at 6 months and to 72.2 +/- 9.9 (P < 0.01) at 18 months (Kruskal
      Wallis analysis: P < 0.0001). PTH showed a biphasic pattern with an initial
      decrease from 39.3 +/- 4.1 ng L-1 at baseline to 22.0 +/- 2.8 ng L-1 at 2 months,
      but increasing thereafter to 45.9 +/- 5.7 at 6 months and 74.2 +/- 8.9 at 18
      months (Kruskal-Wallis analysis: P < 0.001). These variations represent a
      glucocorticoid-induced osteoporosis. In summary, cardiac transplant patients lose
      bone immediately after transplantation at the spine and the hip. Later on, the
      loss in BMD discontinues at all sites of the skeleton, but predominantly at the
      spine, and a few patients still lose bone at the hip. This is probably a result
      of the high bone turnover either due to secondary hyperparathyroidism or induced
      by cyclosporin A.

PMID- 8864417
TI  - Renovascular hypertension and insulin sensitivity.
AB  - We tested the hypothesis that the status of the renin-angiotensin-aldosterone
      system affects insulin sensitivity. Insulin sensitivity (by the euglycaemic
      insulin clamp technique) was measured in eight patients with angiographically
      proven renovascular hypertension and in eight normotensive subjects matched for
      age, gender, body mass index and glucose tolerance. In the patients, insulin
      sensitivity was measured both at baseline and following 7 days of ACE inhibition.
      Following glucose ingestion, patients and controls showed similar insulin and
      glucose responses. Insulin infusion (7 pmol min-1 kg-1) promoted similar glucose
      utilization in the hypertensives and normotensives: 24.8 +/- 2.3 vs. 26.0 +/- 3.0
      mumol min-1 kg-1 respectively. One week of ACE inhibition caused a 20 +/- 4 mmHg
      decrease in mean blood pressure and a 20 +/- 6% decrease in peripheral vascular
      resistance. Plasma angiotensin II concentrations dropped from 24.6 +/- 6.3 to
      13.5 +/-5.0 pg mL-1 (P < 0.05) and plasma aldosterone from 17 +/- 4 to 9 +/- 2 ng
      dL-1 (P < 0.05), and plasma renin activity doubled (from 1.6 +/- 0.3 to 3.4 +/-
      1.7 ng mL-1 h-1, P < 0.02). Nevertheless, insulin sensitivity was unchanged
      (before, 24.8 +/- 2.3; after 25.8 +/- 2.2 mumol min-1 kg-1, P = Ns). During
      insulin infusion, forearm blood flow did not change from baseline in either set
      of studies. Also, the antinatriuretic (before, -26 +/- 18; after, -22 +/- 14%)
      and antikaliuretic (before: -36 +/- 13%, after -39 +/- 11%) action of the hormone
      was unaffected by the therapy. In conclusion, renovascular hypertension is not
      associated with insulin resistance. Furthermore, a selective, drastic reduction
      of the renin-angiotensin-aldosterone system activity and vascular tone does not
      alter insulin action on glucose and electrolyte metabolism.

PMID- 8864418
TI  - Association between eating behaviour and current glycaemic control, body mass or
      autonomic nervous function in long-term type I and type II diabetic patients.
AB  - This cross-sectional study was aimed at investigating the association between
      eating behaviour and current glycaemic control, body mass or autonomic nervous
      function in patients with type I and type II diabetes mellitus (DM). In 72
      patients (31 type I DM, 41 type II DM) we investigated body mass index (BMI),
      serum cholesterol, serum triglycerides, haemoglobin A1c (HbA1c) and autonomic
      nervous function (seven standardized tests). The three-factor eating
      questionnaire was used to investigate cognitive control of eating behaviour (CC)
      and susceptibility to eating problems (SEP). The mathematical product of CC and
      SEP provides information about disinhibition of eating control (DEC). In type I
      DM, there was a correlation between SEP and age (r = -0.536, P < 0.01), SEP and
      HbA1c (0.438, P < 0.05), and between DEC and duration (-0.371, P < 0.05) and DEC
      and HbA1c (0.376, P < 0.05). In type II DM, there was a correlation between SEP
      and BMI (0.401, P < 0.01) and between DEC and BMI (0.429, P < 0.01). Low CC was
      associated with autonomic nervous dysfunction in type I DM (P = 0.022). In type
      II DM, autonomic nervous dysfunction was associated with high SEP (P = 0.044). In
      conclusion, the correlation between eating behaviour and HbA1c or triglycerides
      in type I DM indicates that the questionnaire is able to address current
      parameters of diabetes control. Self-assessment of eating behaviour in type I and
      type II diabetic patients reveals associations between eating behaviour and
      autonomic nervous function.

PMID- 8864419
TI  - Activation of endothelial cells during insulin-dependent diabetes mellitus: a
      biochemical and morphological study.
AB  - Plasma membrane lipid dynamics and cellular morphology were evaluated in
      endothelial cells obtained from umbilical cords of five women affected by insulin
      dependent diabetes mellitus (IDDM) and six healthy pregnant women of similar age
      and gestational age. Endothelial cells were prepared by an adaptation of the
      method of Jaffe et al. Membrane fluidity was studied by means of the steady-state
      fluorescence anisotropy (r) of 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5
      hexatriene (TMA-DPH), a fluorescent probe specifically anchoring at the membrane
      surface. Fluid phase endocytosis was evaluated by the measurement of the changes
      in fluorescence intensity of TMA-DPH at various times, owing to the
      internalization of the fluorescent marker in endocytic vesicles. The
      morphological and morphometric studies were performed by means of transmission
      electron microscopy (TEM). Endothelial cells obtained from IDDM women showed: (a)
      increased fluidity of the superficial region of the plasma membrane; (b) a more
      active fluid phase endocytosis compared with cells from healthy women; (c)
      increase in mitochondrial area, Weibel-Palade bodies and rough reticulum with
      wide cisternae. No statistically significant correlation was found between
      metabolic control and membrane fluidity and endocytosis. All the observed
      modifications suggest the presence of endothelial cell activation with membrane
      reshaping during IDDM. These alterations might play a central role in the
      pathophysiology of atherosclerosis and microangiopathy associated with diabetes
      mellitus.

PMID- 8864420
TI  - Intestinal phase of human antro-pyloro-duodenal motility: cholinergic and CCK
      mediated regulation.
AB  - In this study the muscarinic receptor antagonist atropine and the cholecystokinin
      (CCK)-A receptor antagonist loxiglumide were used to investigate the relative
      importance of cholinergic and CCK-mediated regulation of intestinal phase antro
      pyloro-duodenal motility. Plasma levels of gastrointestinal hormones [pancreatic
      polypeptide (PP), gastrin, CCK] were concomitantly determined to estimate
      biological potency of the doses of the receptor antagonists. In eight healthy
      male volunteers, a 30-min basal interdigestive period was followed by duodenal
      perfusion of a mixed liquid meal for 150 min at 1.6 kcal min-1 against a
      background of saline or atropine (5 micrograms kg-1 h-1) or loxiglumide (10 mg kg
      1 h-1). Antropyloro-duodenal motility was continuously monitored with a sleeve
      straddling the pylorus. Against a background of saline, duodenal nutrients
      persistently stimulated isolated pyloric pressure waves. After 60 min, the
      initially low antral and duodenal contraction rates increased. In the fed state,
      atropine reduced total number of antral contractions and integrated motility
      index by 73% (P < 0.01) and 76% (P < 0.005), total number of pyloric contractions
      and integrated motility index by 43% and 50% (P < 0.05) with inhibition
      increasing over time. It did not alter duodenal contraction frequency but
      diminished duodenal motility index by 39% (P < 0.05) owing to a reduction in
      amplitude and duration of contractions. Loxiglumide decreased total numbers of
      antral, pyloric and duodenal contractions by 44% (P < 0.05), 74% (P < 0.005) and
      41% (P < 0.005) respectively. It reduced cumulative antral, pyloric and duodenal
      motility indexes by 60% (P < 0.01), 80% (P < 0.01) and 61% (P < 0.05)
      respectively. Atropine fully abolished PP release to duodenal nutrients whereas
      loxiglumide reduced it by 60% (P < 0.05). Both atropine and loxiglumide enhanced
      gastrin release whereas only loxiglumide markedly stimulated CCK release. We
      conclude that both cholinergic input and endogenous CCK are major stimulatory
      regulators of antro-pyloroduodenal motility in the intestinal phase. There
      appears to be a regional heterogeneity of cholinergic and CCK control.
      Cholinergic input predominates in the antrum. Both systems are equipotent at the
      pylorus. CCK predominates in the duodenum. We suggest that CCK primarily
      interacts with receptors on cholinergic neurons in the antropyloric region and
      primarily affects smooth muscle receptors in the duodenum.

PMID- 8864421
TI  - Renal and hormonal actions of atrial natriuretic peptide during angiotensin II or
      noradrenaline infusion in man.
AB  - In order to study the renal and hormonal actions of atrial natriuretic peptide
      (ANP) during background infusions with angiotensin II (ANG II) or noradrenaline
      (NA), 69 healthy subjects were examined in three main groups receiving a 90-min
      infusion with either placebo, ANG II (1.5 ng kg-1 min-1), or NA (25 ng kg-1 min
      1). Each of these three main groups were subdivided into two groups receiving an
      infusion with either placebo or ANP (10 ng kg-1 min-1) for the last 60 min of the
      background infusion. Lithium clearance was used to evaluate segmental tubular
      reabsorption. ANG II alone caused a decrease in glomerular filtration rate (GFR),
      renal plasma flow, urinary absolute and fractional excretion of sodium, both
      proximal and distal fractional tubular sodium reabsorption, and urinary flow. NA
      alone caused a decrease in renal plasma flow. ANP alone caused a decrease in
      renal plasma flow. Urinary absolute and fractional excretion of sodium were
      increased and the distal fractional tubular reabsorption of sodium decreased,
      whereas the proximal fractional tubular reabsorption was unchanged by ANP. ANG II
      + ANP: during a background ANG II infusion, ANP still increased fractional
      excretion of sodium. Proximal fractional reabsorption was decreased, whereas
      distal fractional reabsorption of sodium was unchanged by ANP during ANG II
      infusion. The ANP-induced decreases in proximal absolute (-147 vs. +714 mumol min
      1 1.73 m-2, P = 0.05) and fractional (-1.7% vs. +0.6%, P < 0.01) tubular sodium
      reabsorption were more pronounced, and the decrease in distal fractional tubular
      reabsorption of sodium (-0.1% vs -1.4%, P < 0.05) less pronounced compared with
      when ANP was given alone. NA + ANP: during a background NA infusion, ANP still
      increased urinary sodium excretion and decreased distal fractional reabsorption.
      None of the ANP-induced absolute changes seen during background infusion with NA
      were significantly different from the ANP-induced changes seen during placebo
      background infusion. It is concluded that the natriuretic action of low-dose ANP
      seems to be preserved during background infusions with ANG II and NA in man. Net
      sodium excretion during the combined infusion with ANG II and ANP seems to
      reflect the sum of the opposing influences of each peptide. Low-dose ANP had a
      very modest but significant inhibitory effect on proximal tubular sodium
      reabsorption prestimulated by ANG II infusion.

PMID- 8864422
TI  - Detection of gram-negative bacteraemia in early sepsis by a quantitative
      chromogenic and kinetic endotoxin assay. The Study Group.
AB  - A kinetic chromogenic limulus test was carried out in order to investigate the
      possibility of a sensitive and specific detection of circulating endotoxin during
      the first 24 h of septic shock or severe sepsis in 76 patients. Two commercial
      kits, Whittaeker (W) and Chromogenix (C), were used. Blood culture was taken as a
      reference. At 1:10 plasma dilution (a currently used dilution in the end point
      limulus test) abnormal reaction kinetics were found in 13% and 41% of tests, for
      C and W respectively (P = 0.0008), resulting in unreliable results. Retesting
      plasma at a greater dilution, until the reaction kinetic was identical to
      calibration curve control values, gave similar results between the two kits and a
      better accuracy. Beyond a 0.5 EU mL-1 endotoxin level, the probability of Gram
      negative bacteraemia was high (sensitivity = 0.53 and 0.47; specificity = 0.95
      and 0.93 for C and W respectively). This kinetic limulus amoebocyte lysate (LAL)
      test may be useful in therapeutic decisions for treatment of endotoxaemia.

PMID- 8864423
TI  - Effects of bile salt hydrophobicity on crystallization of cholesterol in model
      bile.
AB  - Precipitation of cholesterol crystals is an essential step in gallstone
      formation. In the present study we found much faster and more extensive
      precipitation of various cholesterol crystal shapes in whole model biles
      containing the hydrophobic bile salt taurodeoxycholate than in biles containing
      the relatively hydrophilic taurocholate. Addition of taurodeoxycholate to
      isolated cholesterol-phospholipid vesicles also induced more crystallization than
      taurocholate. Crystallization behaviour in whole model biles and in vesicles
      after addition of corresponding bile salts was very similar. The very hydrophilic
      bile salts tauroursodeoxycholate and taurohyodeoxycholate never induced
      crystallization from vesicles, and crystallization in corresponding whole model
      biles did not occur. These bile salts also reduced crystallization dose
      dependently after addition of taurodeoxycholate to vesicles. Ultracentrifugation
      experiments suggested a higher vesicular cholesterol-phospholipid bile salts.
      These findings indicate that bile salt hydrophobicity influences shape of
      cholesterol crystals and extent of crystallization, possibly by modulating the
      vesicular cholesterol-phospholipid ratio.

PMID- 8864424
TI  - Tumour necrosis factor alpha stimulates gastrin release from canine and human
      antral G cells: possible mechanism of the Helicobacter pylori-gastrin link.
AB  - There is evidence that gastric Helicobacter pylori (Hp) infection promotes
      duodenal ulceration by releasing gastrin. We therefore asked how Hp releases
      gastrin. Tumour necrosis factor alpha (TNF-alpha) is up-regulated in Hp gastritis
      and stimulates hormone release from pituitary cells, so we tested its effect on
      primary cultures of canine antral G cells and human antral fragments. TNF-alpha
      pretreatment (100 ng mL-1) of canine G cells significantly increased both basal
      (by 89%: P < 0.01) and bombesin-stimulated (by 39% P < 0.05) gastrin release. A
      similar pattern of increase was seen following TNF-alpha (20 ng mL-1)
      pretreatment of human antral fragments: basal gastrin release was increased by
      38% (P < 0.05) and bombesin-stimulated by 26% (P < 0.05). This effect persisted
      during immunoblockade with anti-somatostatin antibody S6. We propose that TNF
      alpha provides the link between Hp infection and gastrin release and thus
      contributes to duodenal ulceration.

PMID- 8864426
TI  - Surface tension measurements on pharyngeal and tracheal aspirate samples from
      newborns without and with respiratory distress syndrome.
AB  - A rapid test determining surfactant deficiency or dysfunction might help in
      controlling therapy of respiratory distress syndrome (RDS). Forty tracheal
      aspirate samples (TA) from 40 newborns with RDS (group 1) and 46 pharyngeal from
      46 newborns without RDS (reference group) were analyzed by surface tension
      measurement with the pulsating bubble surfactometer. Five surface tension
      parameters were compared. Marked differences between both groups could be noted
      for the parameters: minimum surface tension (gamma min) and stability index (S),
      while maximum surface tension (gamma max), surface tension after a 10-second
      adsorption period and hysteresis area did not have striking differences. The
      parameters gamma min and S have the highest diagnostic value for determining
      surfactant deficiency or dysfunction. For a rapid test it is sufficient to
      compare gamma min with reference values, because S is calculated from gamma min
      and gamma max.

PMID- 8864425
TI  - Intravenous immune globulin in neonatal ABO isoimmunization: factors associated
      with clinical efficacy.
AB  - OBJECTIVE: Intravenous immune globulin (IVIG) reduces jaundice in many but not
      all cases of neonatal isoimmunization. We sought to elucidate the type of infant
      most likely to benefit from IVIG administration by attempting to define
      pretreatment parameters associated with both clinical symptomatology and
      therapeutic responsiveness to IVIG. METHODS: Term, healthy Coombs-positive
      infants were studied prospectively. IVIG was administered if, despite
      phototherapy, serum bilirubin reached > or = 222 mumol/l (13 mg/dl) at < or = 24
      h of age and/or > or = 274 mumol/l (16 mg/dl) at > 24 h of age. Clinical data
      including serial serum total bilirubin levels, rate of bilirubin rise on day 1 of
      life, serial corrected carboxyhemoglobin levels (a sensitive indicator of
      hemolysis) and total hemoglobin (tHb) levels were collected. RESULTS: Infants
      were classified as IVIG responders (n = 18), those in whom total serum bilirubin
      levels either remained stable or decreased following IVIG administration; IVIG
      nonresponders (n = 5), those who developed a total serum bilirubin of > or = 2
      mg/dl greater than pre-IVIG bilirubin levels within the first 24 h after IVIG
      administration, or nontreated, those not meeting IVIG treatment criteria (n =
      13). Four of the five nonresponders proceeded to require exchange transfusion vs.
      none of the others (p < 0.001). Four of the five nonresponders had a pretreatment
      rate of bilirubin rise of > or = 1 mg/dl/h as compared with only 1 of 18
      responders and none of the nontreated (p < 0.001). Pretreatment tHb levels were
      also different (13.2 +/- 1.3 vs. 15.5 +/- 2.3 vs. 17.7 +/- 2.4 g/dl for
      nonresponders vs. responders vs. nontreated infants, respectively; p < 0.005).
      The highest pretreatment COHbc levels were seen in the nonresponders (1.8 +/- 0.7
      vs. 1.4 +/- 0.3 vs. 0.9 +/- 0.3% tHb, respectively). CONCLUSIONS: Our 3 groups
      represent a spectrum of hemolysis, ranging from severe to moderate to mild. This
      spectrum appears to relate not only to the severity of hemolysis, but also to the
      therapeutic responsiveness to IVIG. We speculate that some or all of the factors
      identified can be used prospectively to predict the subsequent clinical course of
      ABO-incompatible infants and to facilitate optimal management.

PMID- 8864427
TI  - Effects of cordocentesis on inferior vena cava velocity waveforms: differences
      between normally grown and growth-retarded fetuses.
AB  - The objective of this study was to analyze the effects of cordocentesis on
      velocity waveforms recorded from the inferior vena cava and to evaluate
      differences, if any, in the hemodynamic response between normally grown and
      growth-retarded fetuses. Twenty-five normally grown fetuses and 20 growth
      retarded fetuses were considered for this study. This latter group was
      characterized by abnormal Doppler indices in the umbilical artery and the middle
      cerebral artery suggestive of uteroplacental insufficiency as the causative
      factor of the impaired growth. Flow velocity waveforms were measured from the
      inferior vena cava immediately before and after cordocentesis and the % reverse
      flow during atrial contraction calculated. In normally grown fetuses the %
      reverse flow values did not vary significantly after cordocentesis, while in
      growth-retarded fetuses this index increased significantly after the procedure (p
      < or = 0.001). Furthermore, the amplitude of this increase was inversely related
      to pH levels in umbilical vein (p = 0.004). In conclusion, in growth-retarded
      fetuses cordocentesis induces an increase of % reverse flow in the inferior vena
      cava, while no modifications occur in normally grown fetuses. This suggests the
      presence in growth-retarded fetuses of an impaired cardiac adaptive mechanism to
      cordocentesis that may explain the higher incidence of complications occurring in
      such fetuses.

PMID- 8864428
TI  - Impact of central, obstructive and mixed apnea on cerebral hemodynamics in
      preterm infants.
AB  - The objective of this study was to evaluate the effect of central, obstructive
      and mixed apnea on cerebral total hemoglobin concentration (tHb), which is
      analogous to cerebral blood volume, and to investigate whether tHb alterations
      correlate with bradycardia and arterial desaturation. Measurements were carried
      out on 17 preterm infants (gestational age 26-30 weeks) with frequent apneic
      events. Near infrared spectrophotometry (NIRS) was used to quantify changes in
      tHb. Respiration was monitored by chest movements using impedance pneumography
      and by nasal airflow using a thermistor. In addition, heart rate, arterial oxygen
      saturation, in each infant and esophageal pressure in 3 babies were continuously
      recorded. 130 apneic episodes of > 10 s duration showed four different patterns
      of tHb alterations: (1) no change in tHb (28%); (2) isolated decrease (35%); (3)
      isolated increase (12%), or (4) both combined, an initial decrease followed by an
      increase over the previous baseline level (25%). Obstructive apneic episodes were
      associated with a significantly greater maximum fall in tHb (median 11.5; 5th
      percentile 0 and 95th percentile 30.5 mumol/l) compared to mixed (4.9, 0 and 26.4
      mumol/l) and central events (3.0, 0 and 14.0 mumol/l). Changes in tHb correlated
      with heart rate only in purely central apnea and were not reflected in arterial
      oxygen saturation in any type of apnea. Obstructive apnea was observed to have
      the strongest impact on tHb. As these tHb alterations may exacerbate or cause
      intraventricular hemorrhage, efforts must be made to prevent obstruction of upper
      airways and to focus monitoring on cerebral perfusion.

PMID- 8864429
TI  - Fetal mouse lung ultrastructural maturation is accelerated by maternal
      thyrotropin-releasing hormone treatment.
AB  - Maternal administration of thyrotropin-releasing hormone, alone or in combination
      with corticosteroid, accelerates functional, morphologic and biochemical fetal
      lung maturation. However, the dose-response relationship of maternal thyrotropin
      releasing hormone treatment and acceleration of fetal lung ultrastructural
      maturation or disaturated phosphatidylcholine content has not been investigated.
      We administered (i.p.) saline or thyrotropin-releasing hormone (0.2, 0.4 or 0.6
      mg/kg/dose) to the pregnant Balb/c mouse on days 16 and 17 (b.i.d.) and on day 18
      of gestation (1 h prior to killing). Morphometric ultrastructural analysis and
      quantitation of disaturated phosphatidylcholine content was done on the 18-day
      gestation fetal lung. Maternal thyrotropin-releasing hormone treatment resulted
      in an increase in the number of lamellar bodies and depletion of glycogen in
      fetal lung type II cells, and an increase in the lung airspace to parenchymal
      ratio. In addition, a striking difference in the pattern of lung growth was noted
      in the thyrotropin-releasing-hormone-treated (0.4 and 0.6 mg/kg/dose) groups.
      These lungs had larger air spaces, thinner alveolar septae and more air-blood
      barriers. Maternal thyrotropin-releasing hormone treatment did not influence
      fetal lung disaturated phosphatidylcholine content. We conclude that in the
      mouse, maternal thyrotropin-releasing hormone treatment enhances fetal lung
      structural maturation and propose that thyrotropin-releasing hormone plays a role
      in mammalian fetal lung growth.

PMID- 8864430
TI  - Ontogeny of circulating leucocytes in the fetal guinea pig.
AB  - The ontogeny of leucocytes in the fetal guinea pig was investigated. The total
      leucocyte concentration increased between days 40 and 56, but thereafter was
      unchanged at term (day 68). T and B lymphocytes were detected on day 56 and at
      term, and while T cell concentrations remained constant between day 56 and term,
      the concentration of B cells decreased. The ratio of CD4+ to CD8+ T cells
      increased from 0.9 on day 56 to 3.0 at term. All fetal cell concentrations were
      significantly lower as compared with adult animals. The fetal peripheral blood
      mononuclear cell proliferative responses to mitogenic stimulation increased from
      day 40 to 56, but tended to decrease between day 56 and term. The fetal
      proliferative responses were significantly lower as compared with adults.
      Comparison of these data with previous analyses of the pattern of human fetal
      lymphocyte development indicated that, although there were similarities, such as
      the timing of the first appearance of circulating lymphocytes, there were also
      differences, for example the changes which occur between birth and adulthood,
      between the two species. This suggests that the guinea pig may have a limited use
      as a model of some aspects of the ontogeny of the human immune system.

PMID- 8864431
TI  - Possible mechanism for late gestational development of the antioxidant enzymes in
      the fetal rat lung.
AB  - We hypothesized that a possible mechanism to explain the significant increases
      that occur in the pulmonary antioxidant enzyme (AOE) system late in gestation
      might be an endogenous increase in the normal reactive O2 substrates for these
      enzymes. We found that lung O2 free radical formation increased approximately
      175% between fetal day 18 and birth (p < 0.01). We also found that late fetal rat
      lung mitochondrial and microsomal rates of AOE substrate (H2O2) generation
      increased markedly, and there was also significantly increased lung lipid
      peroxidation products with increasing gestational age. These definite elevations
      in reactive O2 species production in parallel with the time course of
      maturational elevations in the pulmonary AOE system, suggest that increasing
      enzyme substrate concentrations could be a primary controlling mechanism for
      increasing lung AOE gene expression in preparation for birth of the newborn.

PMID- 8864432
TI  - Effects of different surfactant preparations on bacterial growth in vitro.
AB  - Several lines of evidence suggest that surfactant and surfactant proteins may
      have direct effects on inhaled bacteria and are able to interact with lung
      defence mechanisms in many ways. We examined the effect of three different
      surfactant preparations (Alveofact, Survanta and Exosurf) approved for treatment
      of the infant respiratory distress syndrome on different strains of Escherichia
      coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus
      agalactiae which are important neonatal pathogens and on Legionella pneumophila
      serogroup I as a frequent cause of pneumonia in adults. Addition of Survanta to
      saline seemed to delay the reduction of viable bacteria in sterile saline and
      induced a considerably accelerated growth of all examined E. coli strains. As
      opposed to this, addition of surfactant did not influence the kinetics of
      bacterial growth in brain-heart infusion or buffered yeast extract both with the
      exception of Exosurf which exerted an inhibitory effect on the multiplication of
      group B streptococci. Though the exact mechanisms underlying these effects remain
      to be determined, the influence of surfactant therapy on the growth of bacteria
      within the respiratory tract should be taken into account.

PMID- 8864433
TI  - Early infectious complications in autologous bone marrow transplantation: a
      review of 219 patients.
AB  - The objective of this study was to define the incidence, type and timing of early
      infectious complications, occurring within the first 30 days, in autologous bone
      marrow transplant (autoBMT) recipients over a 45-month period, and in addition to
      assess the effects of growth factors and primed peripheral blood progenitor cells
      on the rate of infectious complications. The paper describes a retrospective and
      observational study, carried out at the bone marrow transplantation unit at a
      tertiary referral center. The subjects were two hundred and nineteen patients who
      underwent autologous bone marrow transplantation for a variety of indications
      from April 1989 to December 1992. The median duration of neutropenia after
      autologous bone marrow transplantation was 12 days. There was a direct
      correlation between the duration of neutropenia and the incidence of infectious
      complications. The overall incidence of infections and isolated febrile episodes
      was 35%. Septicemia occurred in 7.8% of patients, pneumonia in 2.7%, skin
      infection in 1.8%, other infections in 2.7% and isolated febrile episodes in
      20.1%. Viridans streptococci were the most common cause of septicemia. Invasive
      fungal infections occurred in only 2.3% of patients. There were no documented
      viral infections. The use of growth factors and primed peripheral blood
      progenitor cells was associated with a shorter duration of neutropenia; a
      decrease in the overall incidence of infections, particularly septicemia and
      fungal infections; a shorter length of stay in the hospital and a lower mortality
      rate in the first 30 days after transplantation. We found a lower incidence of
      bacterial and fungal infections compared to previous studies. The critical factor
      associated with the occurrence of any early infection was the duration of
      neutropenia, which was significantly shortened by the use of growth factors and
      peripheral blood progenitor cells. Septicemia was uncommon in our population and
      viridans streptococci were the most common bloodstream isolates.

PMID- 8864434
TI  - CY/TBI-800 as a pretransplant regimen for allogeneic bone marrow transplantation
      for severe aplastic anemia using HLA-haploidentical family donors.
AB  - Allogeneic BMT is the treatment of choice for patients with SAA who have an HLA
      identical sibling donor. The results, however, have been relatively poor for
      transplants from partially matched family donors or unrelated donors because of
      the high incidence of graft rejection and/or GVHD. Six multiply transfused
      patients received a novel conditioning regimen of CY 200 mg/kg and TBI 800 cGy
      prior to receiving marrow from their HLA-haploidentical family donors. Three
      recipient-donor pairs were mismatched for one HLA locus, one for two loci and two
      for three loci. A combination of MTX and CsA was used for GVHD prophylaxis.
      Engraftment was noted in all six patients. Acute GVHD occurred in four patients,
      two each for grade I and II, respectively. One patient, who was ABO-compatible
      with her donor had delayed onset of pure red cell aplasia (PRCA) which completely
      recovered 6 months after additional immunotherapy with prednisolone. There were
      two deaths; both occurred while patients were on treatment for GVHD. One was from
      systemic fungemia and the other probably from cytomegalovirus interstitial
      pneumonitis (CMV-IP). Four patients (66.7%) have been alive and disease-free for
      more than 8.2, 27.3, 38.4 and 47.2 months after BMT, respectively. The results
      suggest that CY/TBI-800 may be a simple and effective conditioning regimen for
      SAA patients receiving BMT from family members other than HLA-identical siblings.

PMID- 8864435
TI  - Mobilization of peripheral blood progenitor cells for allogeneic transplantation:
      efficacy and toxicity of a high-dose rhG-CSF regimen.
AB  - Mobilization of PBPC was investigated in 19 healthy matched sibling donors using
      two different rhG-CSF regimens. Five donors (median age 39 years, range 17 to 57
      years) received 10 micrograms rhG-CSF/kg bw once daily subcutaneously (s.c.),
      while 14 donors (median age 34 years, range 19 to 56 years) were treated with 10
      12 micrograms rhG-CSF/kg bw twice daily s.c.. Leukapheresis was started on day 4
      of rhG-CSF administration. Cytokine priming as well as collection of PBPCs were
      well tolerated. Application of twice daily rhG-CSF resulted in a higher yield of
      CD34+ cells in leukapheresis products than injection of once daily rhG-CSF. This
      high-dose twice daily rhG-CSF regimen is well tolerated and results in reliably
      high numbers of progenitor cells in the leukapheresis product in healthy donors,
      therefore collection as well as subsequent selection has been facilitated.

PMID- 8864436
TI  - Alloresistance to K locus class I-mismatched bone marrow engraftment is mediated
      entirely by CD4+ and CD8+ T cells.
AB  - Clinical application of approaches to inducing transplantation tolerance that
      involve bone marrow reconstitution will require achievement of engraftment
      without major toxicity to the recipient. These requirements are likely to vary
      according to the type of histoincompatibility between donor and recipient. We
      have attempted to determine the minimal conditioning required to achieve lasting
      mixed allogeneic chimerism and tolerance in the presence of a class I MHC
      disparity by evaluating the host elements that resist alloengraftment. We based
      our approach on a regimen that was shown to induce mixed chimerism in fully MHC
      mismatched strain combinations. Recipient B10.AKM (KkIkDq) mice were treated with
      7 Gy thymic irradiation (TI) and 3 Gy whole body irradiation (WBI) and received
      either anti-CD8 mAb alone or anti-CD4 plus anti-CD8 mAbs before transplantation
      of K locus-disparate B10.MBR (KbIkDq) marrow. All (27 of 27) animals receiving
      both mAbs showed lasting multi-lineage mixed chimerism and donor-specific
      tolerance. In contrast, five of 22 (23%) recipients pre-treated with anti-CD8 mAb
      alone in the same experiments failed to develop lasting multilineage mixed
      chimerism, suggesting that the CD4 T cell subset also participates in resistance
      to class I-mismatched marrow engraftment. We next attempted to determine whether
      or not host non-T cell elements resist allogeneic engraftment by comparing the
      minimum number of syngeneic vs allogeneic BMC required to achieve lasting
      multilineage mixed chimerism. Titrated numbers (10(6) to 10(7)) of B10.MBR
      (KbIkDq) bone marrow cells were administered to B10.AKM recipients treated with
      anti-CD4 and -CD8 mAbs, 3 Gy WBI and 7 Gy TI. All recipients of each marrow dose
      developed lasting multilineage mixed chimerism and showed specific tolerance to
      B10.MBR skin grafts. The level of donor-type repopulation in recipients of each
      dose was not lower than that observed in similarly irradiated recipients in an
      Ly5 congenic, otherwise syngeneic, BMT system. Together, our results suggest that
      CD4+ T cells contribute to resistance to K locus class I-mismatched marrow
      allografts and that resistance is mediated only by CD4 and CD8 T cells, with no
      role for non-T cell host elements.

PMID- 8864437
TI  - Granulocyte-macrophage colony-stimulating factor accelerates hematopoietic
      recovery after autologous bone marrow or peripheral blood progenitor cell
      transplantation and high-dose chemotherapy for lymphoma.
AB  - The use of recombinant human granulocyte-macrophage colony-stimulating factor
      (rhGM-CSF) as an adjunct to autologous bone marrow transplantation (ABMT) or
      peripheral blood progenitor cell (PBPC) transplantation was evaluated in 59
      lymphoma patients. Patients were divided into three groups. In group I (n = 21)
      patients received rhGM-CSF (5 micrograms/kg daily) at the time of PBPC collection
      and during the recovery phase post-infusion. In group II (n = 12) patients
      received rhGM-CSF as an adjunct to ABMT. In group III (n = 26) they were grafted
      with bone marrow without rhGM-CSF. Administration of rhGM-CSF (groups I and II)
      significantly reduced the time to myeloid engraftment, the number of febrile days
      and the median duration of antibiotics administration and of hospital stay when
      compared with the group in which patients did not receive rhGM-CSF. The only
      difference between ABMT and PBPC, given with rhGM-CSF support, was observed in
      the duration of hospitalization (group I > group II, P < 0.05). These data show
      that rhGM-CSF is highly effective in reducing the duration of aplasia following
      BMT and PBPC transfusion, and there appears to be little difference in efficacy
      between these techniques, provided that patients also receive rhGM-CSF.

PMID- 8864438
TI  - Serum interleukin-6 levels during bone marrow transplantation: impact on
      transplant-related toxicity and engraftment.
AB  - The biological properties of IL-6 include the induction of acute phase proteins,
      stimulation of hematopoietic stem cell growth and thrombopoiesis. Serum levels of
      IL-6 were closely monitored in 66 patients before and after allogeneic (n = 37),
      autologous bone marrow transplantation (n = 8) or autologous peripheral blood
      stem cell transplantation (n = 21). Almost every patient showed elevated IL-6
      serum levels during the aplastic phase. Patients then suffered from mucositis,
      had elevated C-reactive protein (CRP) and usually body temperatures of above 38
      degrees C. It was investigated whether IL-6 serum levels, apart from inducing
      acute phase reactions, correlated with transplant-related complications or
      leukocyte and thrombocyte engraftment. By statistical analysis, a correlation was
      found between IL-6 and CRP and between IL-6 and fever. In contrast, no
      correlation was found between IL-6 and elevated serum bilirubin as a marker for
      hepatotoxicity. IL-6 showed a weak negative correlation with leukocyte or
      platelet counts. In contrast, the day of platelet engraftment correlated with the
      day of peak serum IL-6 value, possibly indicating an influence of IL-6 on
      platelet engraftment.

PMID- 8864439
TI  - 4-Hydroperoxycyclophosphamide purged autologous bone marrow transplantation in
      non-Hodgkin's lymphoma patients at high risk of bone marrow involvement.
AB  - Between June 1990 and January 1994, 19 patients with non-Hodgkin's lymphoma (NHL)
      at high risk for bone marrow involvement underwent 4-hydroperoxycyclophosphamide
      (4-HC) purged bone marrow transplantation. Eleven patients had low grade, seven
      intermediate grade and one high grade NHL and 7/19 patients had received three or
      more previous chemotherapeutic regimens. Four patients were transplanted in first
      partial remission (PR) and the remainder in responsive relapse. Fourteen patients
      had bone marrow (BM) involvement at diagnosis and/or at relapse. The median times
      to granulocyte and platelet recovery were 26 and 29 days, respectively. There
      were two toxic deaths and one complete responder developed secondary AML at 31
      months post-BMT. Seventeen of 18 evaluable patients achieved a complete remission
      (CR) and one patient a PR. Fourteen patients (74%) are progression-free at a
      median follow-up of survivors of 34 months (range 29-55). The 3 year event-free
      (EFS) and overall survival (OS) probabilities are both 67%. No statistically
      significant difference was seen between EFS or OS and BM involvement or
      histologic grade at diagnosis. At 29 months, 4/7 patients with a morphologically
      involved BM harvest had relapsed or died compared to 1/12 patients with negative
      BM (P = 0.03). These results are encouraging and warrant further investigation of
      4-HC purging in NHL.

PMID- 8864440
TI  - High-dose melphalan +/- total body irradiation and autologous hematopoietic stem
      cell rescue for adult patients with Ewing's sarcoma or peripheral neuroectodermal
      tumor.
AB  - The role of high-dose therapy and autologous stem cell transplantation (ASCT) in
      the treatment of patients with Ewing's sarcoma (EWS) remains uncertain. From
      November 1985 to September 1994, 13 patients aged 16-30 years (median 20.5)
      received high-dose melphalan (HDM) 140-200 mg/m2 +/- 500 cGy TBI followed by ASCT
      for relapsed/refractory (n = 4), metastatic (n = 2), or non-metastatic (n = 6)
      EWS, or for peripheral neuroectodermal tumor (PNET) (n = 1). This regimen was
      well tolerated with no transplant-related mortality and no toxicity requiring
      life sustaining measures. Three of the four patients treated for
      relapsed/refractory EWS had progression-free survivals (PFS) less than 5 months.
      The only long-term survivor of these four patients received HDM while in complete
      remission following pulmonary irradiation. Both patients with pulmonary
      metastases at presentation died just 5 and 6 months post-ASCT. All four patients
      with non-metastatic, bulky (> 8 cm) osseous EWS progressed at a median of 11
      months (range 7-22 months) while the two patients with non-bulky EWS remain
      progression-free 25+ and 28+ months post-HDM/TBI + ASCT. The 19-year-old patient
      with a PNET of the thoracoabdominal wall relapsed 4 months post-ASCT. Overall,
      only three of these 13 patients remain progression-free at 25+, 28+, and 108+
      months following HDM +/- TBI and ASCT. In conclusion, HDM +/- TBI did not
      obviously improve the outcome of these 13 patients relative to that expected
      following conventional dose therapy alone.

PMID- 8864441
TI  - Factors affecting engraftment and hematopoietic recovery after unpurged
      autografting in acute leukemia.
AB  - Factors affecting hematologic recovery to 0.5 x 10(9)/l neutrophils and 50 x
      10(9)/l platelets after unpurged autografting (210 marrow, 30 blood) were
      analyzed in 240 patients with acute myeloid (AML, n = 128) or lymphoblastic (ALL,
      n = 112) leukemia. Cytokines were not administered routinely after transplant.
      Age, sex and cryopreservation did not influence hematologic recovery in
      multivariate analysis. Blood cell grafts (P < 0.0001), ALL (P = 0.003), and a
      nucleated cell dose of > or = 2 x 10(8)/kg (P = 0.035) were associated with
      faster neutrophil recovery. First remission (P = 0.001), a higher cell dose (P =
      0.011), ALL (P = 0.023), and a short remission-transplant interval (P = 0.023)
      were associated with faster platelet recovery. There was a strong correlation
      between blood cell grafts and higher cell doses, and marrow and lower cell doses.
      Amongst marrow recipients, neutrophil recovery was faster in ALL (P = 0.001) and
      with higher cell doses (P = 0.032). Platelet recovery was faster in first
      remission patients (P = 0.005) and ALL (P = 0.043), and with higher cell doses (P
      = 0.031). We conclude that hematologic recovery after autografting is faster in
      ALL and first remission patients, probably due to the nature and the amount of
      prior chemotherapy. Using blood stem cells hastens engraftment, but even if
      marrow is used due to concern over relapse with blood, higher cell doses are
      associated with faster recovery.

PMID- 8864442
TI  - Previous conventional chemotherapy is the principal risk factor for
      immunoglobulin deficiency during the early post-ABMT period in children.
AB  - Humoral immunodeficiency after ABMT may worsen the course of infectious
      complications as already described in this clinical setting; children with low Ig
      values of the three isotypes during the first week after ABMT experienced more
      severe infections during the procedure than those with normal values. The aim of
      the study was to establish the prevalence, the duration and the risk factors of
      Ig deficiency after ABMT. Serum Ig levels of 160 children treated with high-dose
      chemotherapy (HDCT) followed by ABMT for solid tumors were studied prospectively
      before HDCT and weekly from the day after transplantation until the patients were
      discharged from the unit, as were the associations of the following covariates:
      patient characteristics, previous conventional chemotherapy (CCT), conditioning
      regimens, marrow graft and complications following ABMT. Serum Ig deficiency for
      at least one isotype was already present before HDCT in half of the children and
      mean serum Ig values decreased after HDCT. Serum Ig deficiency was early (day 7),
      inconstant, heterogeneous (IgM deficiency was more frequent and lasted longer)
      and brief (< 1 month). Children with low Ig values before HDCT were at high risk
      of profound and prolonged humoral immune deficiency. Previous CCT with more than
      six different drugs was the main risk factor for low serum IgM values before
      HDCT, on day 7 and on day 21 post-HDCT. This study shows that Ig replacement
      therapy could be useful after ABMT provided it is given to the patients defined
      on the basis of these specific risk factors and serum Ig levels before HDCT.

PMID- 8864443
TI  - Loss of seroreactivity against human papillomavirus (HPV) in bone marrow
      transplant recipients.
AB  - Sera from 19 autologous and 35 allogeneic bone marrow transplant (BMT) patients
      at Huddinge University Hospital were analyzed by different ELISA assays before
      and 1 year after BMT for the presence of IgG antibodies towards human
      papillomavirus (HPV). One assay was a peptide-based enzyme-linked immunoadsorbent
      assay (ELISA). These peptides were derived from the amino acid sequences of the
      two major viral capsid proteins of HPV 16, p(31) L1 and (p49) L2. The other was
      an ELISA using HPV-type 16 virus-like particles (VLPs) as antigens. Before BMT
      13/19 autologous and 14/35 allogeneic BMT patients were IgG positive towards p49
      (L2). Reactivity to p31 (L1) was less frequent and was only observed in 7/19
      autologous and 3/35 allogeneic BMT patients. One year after BMT 1/4 of the
      autologous and 2/3 of the allogeneic BMT patients who were IgG positive to p49
      (L2) lost these antibodies as measured by the peptide ELISA assay. Regarding IgG
      reactivity to p31 (L1), one of the seven p31 (L1) positive autologous BMT
      patients and all three of the p31 (L1) positive allogeneic BMT patients lost this
      reactivity 1 year after BMT. Of all the 19 autologous and the 35 allogeneic BMT
      patients only two allogeneic BMT patients were weakly IgG reactive towards VLPs
      and 1 year after BMT this activity was lost in one of the two patients.

PMID- 8864444
TI  - Clonal predominance of cytomegalovirus-specific CD8+ cytotoxic T lymphocytes in
      bone marrow recipients.
AB  - After lymphocyte-depleted BMT, CD8+ T cells have been expanded to or above normal
      levels in 45% of the recipients within 3 months. The mechanisms underlying
      proliferation of donor-derived CD8+ T cells after BMT are still unclear. We
      investigated whether these CD8+ T cells proliferate in response to specific
      antigens by determination of TCR clonality and whether these cells exert specific
      cytotoxicity. PCR analysis of TCR-gamma gene rearrangements showed a marked
      clonal predominance in CD8+ T cells of recipients with a high number of these
      cells. Strong association between expansion of CD8+ T cells and CMV infection
      suggests involvement of CMV antigens. Therefore, we examined CMV-specific
      cytotoxicity of freshly isolated CD8+ T cells of two BMT recipients with clonal
      expansion after the onset of CMV infection. CD8+ T cells exerted HLA-restricted
      cytotoxicity directed against CMV-infected fibroblasts indicating that CMV
      stimulates proliferation. The majority of CD8+ T cells in these recipients
      expressed CD57. We demonstrated that TCR clonality was irrespective of CD57
      expression. Both CD8+CD57+ and CD8+CD57- T cells showed significant HLA
      restricted CMV-specific cytotoxicity. These studies strongly suggest that CMV
      antigens can induce expansion of clonal CD8+ T cells after BMT.

PMID- 8864445
TI  - Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis
      following T-depleted BMT for adults with hematological malignancies.
AB  - Reactivation of cytomegalovirus (CMV) is a major cause of morbidity and mortality
      following allogeneic bone marrow transplantation (BMT) and early reactivation
      with increased risk of interstitial pneumonia (IP) has been reported in T cell
      depleted BMT. In 21 patients at risk for CMV reactivation following T cell
      depleted BMT for hematological malignancies, CMV reactivation was the main cause
      of transplant-related mortality: 19 (90.5%) reactivated CMV and five (26%
      actuarial) developed fatal IP. Median reactivation time post-BMT was 22 days for
      IP and 39.5 days for non-IP patients (P = 0.04). Patients developing IP showed no
      increase in lymphocyte count following CMV reactivation. There was a trend for
      higher pp65 antigen load at reactivation in patients who relapsed with CMV or
      progressed to IP. Donor lymphocyte transfusions (DLT) were given to pre-empt
      leukemic relapse and viral infection (15 patients) or to treat IP in two. Nine of
      19 patients reactivated CMV before receiving DLT on day 30 post-BMT and DLT were
      ineffective in established IP. However DLT from seropositive donors did not cause
      IP. These results confirm the relationship of donor T cell function with CMV
      reactivation following BMT. They suggest that patients receiving T cell-depleted
      BMT should be protected from CMV disease with prophylactic rather than pre
      emptive treatments.

PMID- 8864446
TI  - Infectious complications of autologous bone marrow and peripheral stem cell
      transplantation for refractory leukemia and lymphoma.
AB  - We aimed to characterize the infectious complications of autologous bone marrow
      (AuBMT) and peripheral stem cell transplantation (PSCT) in patients with
      refractory leukemia and lymphoma. We performed a retrospective analysis of all
      patients (n = 56) with refractory leukemia or lymphoma treated with AuBMT or PSCT
      at Memorial Sloan-Kettering Cancer Center from January 1993 to July 1994. Records
      were available in 55, of whom 33 (60%) received AuBMT and 22 (40%) PSCT. Fifteen
      (27%) developed complicated infections, including 13 (39%) treated with AuBMT and
      two (9%) with PSCT. Complicated infections were caused by bacterial (11
      episodes), fungal (four episodes), and viral (four episodes) pathogens. Five (9%)
      infections were fatal. In a multivariate model, only duration of neutropenia was
      significantly associated with development of complicated infection (P = 0.006).
      Thus, 27% of patients with refractory leukemia or lymphoma treated with AuBMT or
      PSCT developed complicated infections and 9% died of infection. Prolonged
      neutropenia was significantly associated with development of infection. Patients
      receiving PSCT had significantly lower rates of complicated infection, presumably
      due to the associated shorter duration of neutropenia. Future studies are needed
      to define the role of PSCT as treatment for refractory neoplastic disease.

PMID- 8864447
TI  - Legionellosis in a bone marrow transplant center.
AB  - We reviewed 10 cases of culture proven legionellosis that occurred at a marrow
      transplant center (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) over
      a 6-year period ending in 1993. Infections were caused by four species of
      Legionella with no apparent clustering of cases. Detection of Legionella using
      direct fluorescent antibody assays proved unreliable due to the high proportion
      of rare Legionella species isolated. The clinical presentation, course and
      outcome of patients varied and did not correlate with underlying disease, type of
      transplant, transplant day or engraftment status. However, five of the seven
      patients infected with non-pneumophila species recovered from their pneumonia
      compared to none of the three patients infected with L. pneumophila. Persistent
      or relapsed infection after 3 weeks of appropriate therapy was documented in one
      case suggesting that prolonged antibiotic treatment is indicated in these
      patients.

PMID- 8864448
TI  - Murine IL-10 fails to reduce GVHD despite inhibition of alloreactivity in vitro.
AB  - Graft-versus-host disease (GVHD) is a serious complication following allogeneic
      bone marrow transplantation (BMT). Initial immunologic events that are thought to
      lead to clinical GVHD include allogeneic antigen presentation, CD4+ T cell
      proliferation and eventually generation of specific cytotoxic lymphocytes.
      Interleukin-10 (IL-10) has been shown to inhibit the function of antigen
      presenting cells (APC) and to reduce lymphocyte proliferation. In this study we
      investigated the possible role of recombinant murine IL-10 (rmIL-10) as
      prophylactic treatment of GVHD in a murine BMT model involving B10.BR donor mice
      (H-2k) and AKR recipients (H-2k). In particular, we wished to determine whether
      early post-BMT administration of IL-10 would suppress GVHD by interfering with
      macrophage function and inflammatory cytokine production during the proposed
      "afferent' phase of GVHD. In MLR assays, rmIL-10 significantly inhibited the
      proliferation of donor spleen cells when stimulated by irradiated recipient
      spleen cells in a dose-dependent manner. In murine BMT, rmIL-10 was administered
      exogenously by intraperitoneal injection of 100 U daily in two different dosage
      schedules, on days-1, 0, 1, 2, 3, 6 to target the early post-BMT phase, and days
      1, 0, 3, 5, 7, 10 after BMT, to administer the same total dose throughout the
      engraftment period. IL-10 injected mice had lower plasma IL-1 alpha levels on day
      3 (12 pg/ml vs 64 pg/ml in controls, P < 0.05), suggesting that both macrophage
      function and inflammatory cytokine production were inhibited. In contrast to the
      MLR data, no significant improvement in morbidity and mortality from GVHD was
      observed. Therefore, IL-10 does not appear to be useful in GVHD prophylaxis.

PMID- 8864449
TI  - Risk factors for developing EBV-related B cell lymphoproliferative disorders
      (BLPD) after non-HLA-identical BMT in children.
AB  - B cell lymphoproliferative disorders (BLPD) are relatively frequent after
      genotypically non-HLA-identical BMT. We performed univariate analysis to study
      which BMT-related variables were associated with an increased risk of developing
      BLPD. Sixty-five recipients of other than genotypically HLA-identical BM grafts
      were included in the study. Seventy-seven recipients of genotypically HLA
      identical BM grafts served as a comparison group. BLPD occurred in nine of 65
      children after non-HLA-identical BMT (14%) and in none of the 77 children after
      HLA-identical BMT (0%). In all cases, BLPD was proven to be EBV-related. Our data
      suggest that the combined use of Campath 1G and anti-LFA1 was associated with an
      increased risk of developing BLPD, particularly children who had received a T
      cell-depleted BM graft, using albumen density gradient sedimentation followed by
      E-rosetting, and who were conditioned with Ara-C, CY and TBL. In addition, T cell
      numbers below 50/microliters at 1 month and below 100/microliters at 2 months
      after BMT, respectively, were associated with an increased risk of developing
      BLPD. Longitudinal determination of T cell numbers after non-HLA-identical BMT is
      a simple method for identifying patients at risk of developing BLPD. In addition
      to monitoring levels of circulating EBV-infected lymphocytes, monitoring T cell
      numbers may allow early intervention to prevent progression of BLPD.

PMID- 8864451
TI  - Complete donor T cell chimerism is accomplished in patients transplanted with
      bone marrow grafts containing a fixed low number of T cells.
AB  - T cell depletion of the bone marrow graft, the most effective method to prevent
      severe graft-versus-host disease (GVHD) after allogeneic bone marrow
      transplantation (BMT), has resulted in approximately three times more relapses of
      the disease post-transplant than after non-T cell-depleted BMT. It has been
      hypothesized that this is caused by the development of mixed T cell chimerism,
      often observed after T cell depleted BMT, whereas non-T cell-depleted BMT
      generally results in complete donor T cell chimerism. In order to find an
      approach of T cell depletion which may avoid the high relapse rate but prevent
      severe GVHD, we gave marrow recipients a partial T cell-depleted marrow graft
      containing 1 x 10(5) donor T cells/kg recipient's weight. To investigate whether
      our approach results in complete donor T cell chimerism, we analyzed post
      transplant the origin of purified T cells in 56 patients with hematologic
      malignancies, including 15 patients at the time they relapsed. The T cells were
      studied for being of host or donor origin by amplification of four loci of
      variable number of tandem repeats (VNTR) by PCR. From 6 months post-BMT, all 45
      patients who could be analyzed in remission (five had died and six had relapsed
      within 6 months) had T cells that were exclusively of donor origin. Furthermore,
      the T cells of 15 patients who had relapsed post-BMT were also exclusively of
      donor origin. Severe GVHD was never observed. Thus, this approach seems to
      combine the favorable aspects of both T cell-depleted and non-T cell-depleted
      BMT.

PMID- 8864450
TI  - Increased plasma level of vascular endothelial glycoprotein thrombomodulin as an
      early indicator of endothelial damage in bone marrow transplantation.
AB  - We investigated the nature of hemostatic alterations occurring after bone marrow
      transplantation. In 45 patients, we evaluated the coagulation parameters,
      naturally occurring anticoagulants and thrombomodulin at days +15 and +22 after
      conditioning therapy. It was observed that endothelial cell damage is a central
      pathogenetic mechanism in some BMT complications. The increased plasma level of
      thrombomodulin after conditioning therapy is therefore discussed as a marker of
      endothelial cell injury. At day +15 a significant increase of fibrinogen from
      276.1 mg/dI to 389.1 mg/dI was observed, while the natural anticoagulants all
      decreased significantly. Eleven patients with clinical complications related to
      endothelial damage had a significant thrombomodulin increase which, in
      uncomplicated patients, remained unchanged or resulted in lower than baseline
      values. Analysis of the data shows a strong correlation between clinical
      findings, reflecting endothelial cell injury and thrombomodulin increase when the
      increment is > or = 30%. We found a significant elevation in thrombomodulin in
      70% of clinical complications related to endothelial cell damage namely:
      septicemia, GVHD, VOD. There were four cases (or 9%) of false positive data, and
      only two (or 4.5%) of false negative results. We therefore propose thrombomodulin
      assessment as a valid parameter to monitor chemotherapy toxicity-related
      complications.

PMID- 8864452
TI  - Molecular studies of chimerism and minimal residual disease after allogeneic
      peripheral blood progenitor cell or bone marrow transplantation.
AB  - We investigated 23 patients for their chimerism status who underwent allogeneic
      transplantation using peripheral blood progenitor cells (PBPCT) for chronic
      myelogenous leukemia (CML) (n = 14), acute myelogenous leukemia (AML) (n = 5),
      acute lymphoblastic leukemia (n = 1), myelodysplasia (MDS) (n = 1), and Hodgkin's
      disease (HD) (n = 2). These data were compared with those of patients after
      allogeneic BMT after matching them for disease and disease stage, sex of donor
      and recipient, GVHD prophylaxis, conditioning therapy and degree of HLA
      disparity. Patients were studied monthly up to 16 months post-transplant. In 11
      of 23 (48%) patients who were transplanted with PBPCs and in 18 of 23 (78%)
      patients after BMT a mixed chimerism was detected at 1 month post-transplant.
      After 3 months, six of 21 (29%) evaluable patients after PBPCT remained mixed
      chimeric as opposed to 12 of 21 (57%) patients after BMT. We also assessed
      minimal residual disease using detection of the chimeric BCR/ABL transcripts by
      PCR of CML patients in this study. In four of 14 (29%) patients who underwent
      PBPCT, the BCR/ABL chimeric transcript was detected, while after BMT eight of 14
      (57%) CML patients remained BCR/ABL positive. In two of these BMT patients, a
      cytogenetic relapse developed subsequently, and one other patient suffered a
      hematological relapse, whereas one of the CML patients relapsed after PBPCT. The
      present data may indicate that after PBPCT the incidence of leukemic relapse is
      similar or even lower than after BMT.

PMID- 8864453
TI  - Study of chimerism in long-term survivors after bone marrow transplantation for
      severe acquired aplastic anemia.
AB  - Chimerism studies employing PCR and Southern techniques targeting VNTR loci were
      performed in 17 severe acquired aplastic anemia patients who were long-term
      survivors after BMT. They were studied a median of 4 years after BMT (1-12). All
      patients had normal blood counts. All patients conditioned with radiation-based
      schemes showed a full donor pattern of hemopoiesis. Conversely, out of five
      patients who received only cyclophosphamide as conditioning therapy, two of them
      had a late graft failure (2.4 and 3 years after BMT). One of these relapsing
      patients had a durable mixed chimerism, which was first detected 1 month after
      BMT. Our results seem to suggest that durable mixed chimerism can antecede graft
      failure in some patients conditioned only with cyclophosphamide, and that a more
      stringent monitoring can be clinically rewarding in this group of patients.

PMID- 8864454
TI  - Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16
      patients.
AB  - Sixteen patients with relapse after allogeneic BMT were treated with donor
      leukocyte infusions (DLI) from the original donor. The diagnoses at relapse were:
      CML in chronic phase (CP) (two patients), CML in accelerated phase (AP) (four
      patients), AML (four patients), MDS (one patient), ALL (four patients) and
      relapse of Hodgkin's disease (one patient). The patients received a mean of 5.2 x
      10(8) leukocytes/kg with a range of 1.4-12.3 x 10(8) leukocytes/kg. Six patients
      obtained complete remission (CR), one with CML in CP, three with CML in AP, one
      MDS and one ALL. Partial remission (PR) was seen in three patients, one patient
      with CML in AP, one with AML and one with Hodgkin's disease. Seven patients had
      no response (NR) to the infusions, including one patient with CML in CP
      transplanted with a syngeneic donor. Four patients developed marrow hypoplasia
      after DLI (three CR and one PR) and two patients (ALL with CR and MDS with CR)
      were hypoplastic at relapse and marrow hypoplasia continued after DLI. GVHD
      occurred without GVL, but GVL only occurred in one patient with absence of GVHD.
      Eleven patients died of leukemia, six patients are alive. Three patients with CML
      are in CR 12, 12 and 32 months after DLI and one patient with ALL is in CR 15
      months after DLI.

PMID- 8864455
TI  - Eliminating graft-versus-host potential from T cell immunotherapeutic
      populations.
AB  - It is common knowledge that donor T cells are responsible for graft-versus-host
      disease (GVHD) following bone marrow transplantation (BMT), yet GVHD remains a
      grave threat to transplant patients. The donor marrow can be purged of T cells to
      reduce this danger, but the risks of viral infections, tumor relapse and graft
      rejection are then increased. Here we describe a method that may be used to
      provide BMT patients with T cell immunotherapeutic populations responsive to
      foreign antigens, but unresponsive to host HLA. The method involves the culture
      of donor T cells with host-derived B lymphoblastoid cell lines (BLCL). During
      culture, the T cells are activated by the mismatched host HLA. Activated cells
      are subsequently removed by fluorescence-activated cell sorting. Criteria for
      removal include cell size and the expression of multiple T cell activation
      antigens on cell membranes. After the procedure, T cell populations retain helper
      and cytotoxic T cell responses against foreign antigens, but are specifically
      devoid of responses to host HLA. This technique offers a promising method for
      providing BMT patients the benefits of T cell immunity without the consequences
      of GVHD.

PMID- 8864456
TI  - Separation of chemotherapy plus G-CSF-mobilized peripheral blood mononuclear
      cells by counterflow centrifugal elutriation: in vitro characterization of two
      different CD34+ cell populations.
AB  - Counterflow centrifugal elutriation (CCE) has been extensively employed in T cell
      depletion of bone marrow cells for allografting. Nevertheless very little is
      known about CCE properties of mobilized hematopoietic progenitors. In this study
      five leukapheresis products collected after chemotherapy and G-CSF from patients
      with non-Hodgkin's lymphoma were elutriated. Two mononuclear cell fractions were
      obtained containing smaller and less dense cells (lymphocyte fraction) and larger
      and denser cells (monocyte fraction), respectively. The presence of immature
      CD34+ progenitor cells, not co-expressing CD33, CD38 and HLA-DR antigens, was
      demonstrated in both cell fractions. CD34+ cells were isolated from each fraction
      and grown in various culture conditions (CFU-GM and BFU-E assay, blast cell
      colony assay, cytokine supplemented liquid culture). CD34+ cells isolated from
      the monocyte fraction showed a longer lasting expansion in liquid culture and a
      higher number of blast cell colonies than CD34+ cells selected from the
      lymphocyte fraction. Moreover a significant reduction of T cell number was
      obtained in the monocyte fraction. These data suggest that chemotherapy plus G
      CSF-mobilized progenitor cells show a characteristic behavior when subjected to
      CCE, allowing an efficient T cell depletion without losing more immature
      progenitors.

PMID- 8864457
TI  - G-CSF (filgrastim)-stimulated whole blood kept unprocessed at 4 degrees C does
      support a BEAM-like regimen in bad-risk lymphoma.
AB  - The purpose of this study was to demonstrate the reconstitutive potential of
      granulocyte colony-stimulating factor (G-CSF) (filgrastim; Neupogen-primed
      unprocessed whole blood after myelotoxic therapy in bad-risk lymphoma. Nine
      patients with resistant lymphoma were treated with BAM: a BEAM regimen modified
      to a 72 h course consisting of BCNU 300 mg/m2 i.v. (day 1), Ara-C 3000 mg/m2 i.v.
      q 12 h (day 2) and melphalan 140 mg/m2 i.v. (day 3). After 5 days stimulation
      with G-CSF (10 micrograms/kg) 1l of blood was drawn, kept unprocessed for 3 days
      and reinfused 24 h after completion of chemotherapy. Back-up peripheral stem
      cells were available for all patients. The neutrophil count reached 0.5 x 10(9)/l
      at a median of 16 days (range 11-25) and a platelet count of 10 x 10(9)/l was
      reached at a median of 20 days (range 11-NR (not reached)). The median length of
      hospital stay was short in these patients with a median of 19 days (range 17-33).
      In three patients platelet transfusion independence did not occur before day 28.
      Those patients received their back-up stem cells. Antibiotics had to be used in
      two patients. The median number of reinfused CD34+ cells was 0.28 x 10(6)/kg
      (range 0.01-0.59). When more than 0.2 x 10(6)/kg CD34+ cells were reinfused the
      time to recovery was comparable to that observed after 'classical PBSCT'. In
      conclusion, the use of G-CSF-stimulated unprocessed whole blood is easy to
      perform and a cheap technique to mobilize and collect stem cells that can serve
      as a stem cell source after severe myelotoxic therapy in bad-risk malignant
      lymphoma.

PMID- 8864458
TI  - Mixed erythrocyte chimerism: implications for tolerance of the donor immune
      system to recipient non-ABO system red cell antigens.
AB  - We report a case of a minor degree of ABO incompatibility in a BMT recipient,
      demonstrating mixed RBC chimerism, who, late in the post-transplant period,
      developed a warm autoimmune hemolytic anemia and subsequently developed
      antibodies with donor-anti-recipient specificities for non-ABO system RBC
      antigens. While this implies a lack of tolerance of the donor immune system for
      recipient non-ABO system RBC antigens, other factors may be operating and should
      be evaluated before such a conclusion is reached. Underscored is the importance
      of obtaining pretransplant RBC antigen phenotypes on both the recipient and
      donor.

PMID- 8864459
TI  - Proliferation of macrophage-lineage cells in the bone marrow, severe thymic
      atrophy, and extramedullary hematopoiesis of possible donor origin in an autopsy
      case of post-transplantation graft-versus-host disease.
AB  - A case of proliferation of CD68-positive macrophage-lineage cells in the bone
      marrow accompanied by severe thymic atrophy associated with graft-versus-host
      disease (GVHD) in a boy given allogeneic bone marrow transplantation (BMT) is
      reported. A 7-year-old boy was treated for posthepatitic severe aplastic anemia
      by BMT from his HLA-identical, mixed lymphocyte reaction-negative sister. After
      the transplantation his peripheral blood group converted to the donor type.
      However, the patient suffered from acute and chronic GVHD and slowly progressive
      anemia, and he died of multiple organ failure 21 months after BMT. At the autopsy
      diffuse and monotonous proliferation of CD68-positive macrophage-lineage cells
      was found to be replacing the blood-forming cells in the bone marrow. The thymus
      was almost empty of T lymphocytes, and remaining strands of extremely atrophic
      epithelial cells showed focal cystic change. Extramedullary hematopoiesis was
      found in the spleen. Analyses of microsatellite markers suggested the
      hematopoietic cells in the spleen to be of donor origin.

PMID- 8864460
TI  - Successful treatment of severe hepatic veno-occlusive disease after allogeneic
      bone marrow transplantation by transjugular intrahepatic portosystemic stent
      shunt (TIPS).
AB  - Severe veno-occlusive (VOD) disease is a major cause of morbidity and mortality
      in allogeneic bone marrow transplant recipients, and new approaches in managing
      patients who develop serious VOD is needed. In this report, we describe a patient
      who underwent transjugular intrahepatic portosystemic stent-shunt (TIPS) for life
      threatening VOD are following allogeneic bone marrow transplantation for AML.
      Although the patient died of CMV-associated pneumonitis 5 weeks later, the TIPS
      functioned well until her death and permitted regression of the hepatic and renal
      symptoms. This report suggests that TIPS may be feasible and effective for
      managing patients with life-threatening liver dysfunction after marrow
      transplantation.

PMID- 8864461
TI  - Chagas' disease after bone marrow transplantation.
AB  - Chagas' disease is caused by Trypanosoma cruzi. It is endemic in Latin America
      where 16 to 18 million people are infected. Immunocompromised patients such as
      BMT recipients are at risk of Chagas' disease either due to reactivation or
      transfusion. We report a case of acute Chagas' disease in the setting of BMT.

PMID- 8864462
TI  - Allogeneic bone marrow and peripheral stem cell transplantation from a haplo
      identical mother and CD34 positive selection for CML.
AB  - A 6-year-old boy with CML in blastic crisis was transplanted with BM and PBSC
      from his HLA-mismatched MLC-positive mother following CD34-positive selection.
      Preconditioning for transplant was with thiotepa, cyclophosphamide, rabbit anti
      human thymocyte globulin, and TBI followed by infusion of 2.6 x 10(6)/kg of CD34
      positive BM and PBSC. Engraftment was confirmed by FISH analysis, and GVHD was
      not observed. On day 50, he relapsed and died despite three transfusions of donor
      lymphocytes without GVHD prophylaxis. CD34-positive cell selection for HLA
      mismatched transplantation may prevent severe acute GVHD.

PMID- 8864463
TI  - Unrelated donor bone marrow transplantation for acute leukemia in patients with
      Down's syndrome.
AB  - The incidence of hematologic disorders in patients with Down's syndrome (DS) is
      significantly increased, and includes neonatal transient abnormal myelopoiesis
      and acute leukemias. Treatment of children with DS and leukemia has been
      controversial because of toxicity and associated congenital cardiac and other
      abnormalities. The role of BMT, particularly from an unrelated donor (URD),
      remains undefined in this population. We report two children with DS and acute
      leukemia successfully treated with intensive chemotherapy and matched URD bone
      marrow transplantation. One child was transplanted in third remission of ALL and
      has been disease free for 8 months. A second child with AML was transplanted in
      second remission and is disease free 15 months post-BMT.

PMID- 8864464
TI  - Solitary pulmonary cholesteroloma, multiple xanthelasmas and lipemia retinalis
      complicating hypercholesterolemia after bone marrow transplantation.
AB  - A 22-year-old female with diffuse mixed T cell lymphoma in second complete
      remission underwent allogeneic BMT from her HLA-compatible brother.
      Transplantation was complicated by acute graft-versus-host disease (GVHD),
      cytomegalovirus (CMV) infection, and combined hepatotoxic/cholestatic liver
      disease 45 days post-BMT. Cholesterol levels reached 65 mmol/l, and high density
      lipoprotein (HDL) cholesterol decreased to 0.23 mmol/l. She developed skin
      xanthelasmas, lipemia retinalis, and a solitary lung lesion, which was clinically
      diagnosed as pulmonary cholesteroloma. All these complications resolved following
      plasmapheresis and hypolipidemic treatment with lovastatin and cholesterol levels
      normalized.

PMID- 8864465
TI  - Unrelated bone marrow transplantation as a rescue procedure following inadvertent
      loss of an autologous bone marrow graft.
AB  - We report a 27-year-old male patient with acute myeloid leukaemia who was
      successfully treated with an unrelated bone marrow graft within 7 days following
      the loss of his autologous bone marrow graft. Several factors were found to be
      essential in order to locate an HLA-ABDR (DRB1)DQ(DQB1) identical, sex-matched,
      CMV-negative and ABO compatible donor within a week. These included a common HLA
      phenotype of the patient, the presence of an experienced donor registry in close
      proximity to a blood bank associated with an HLA laboratory, a large donor file
      with fully HLA-ABDR typed donors and the almost exclusive use of blood bank
      donors as potential bone marrow donors. The possibility of further streamlining
      the logistics of finding a suitable unrelated bone marrow donor is discussed.

PMID- 8864467
TI  - Unrelated mismatched cord blood transplantation in an adult with secondary AML.
AB  - Umbilical cord blood (CB) has been widely used for related and unrelated
      transplants in pediatric patients. We present the case of an adult with secondary
      AML who received an unrelated, one-antigen mismatched CB transplant due to the
      lack of a matched donor. The patient was a 26-year-old female (35 kg/bw) who had
      received an autologous bone marrow transplant for Hodgkin's disease in April 1994
      and, 6 months later, developed secondary MDS (RAEB, 46, XX, -7, +mar), which
      slowly evolved into acute myelogenous leukemia. In May 1995, she was transplanted
      with a 165 ml CB unit containing a total of 1.6 x 10(9) nucleated cells, 11 x
      10(6) CD34+ cells and 7.2 x 10(5) CFU-GM. GVHD prophylaxis consisted of standard
      CsA and methotrexate. Myeloid engraftment occurred on day +28 (PMN > 500) and
      full donor chimerism was confirmed twice (on days +33 and +56) by means of
      cytogenetics and DNA microsatellite analysis. Erythroid and megakaryocytic
      engraftment was documented by immunohistochemical analysis of a bone marrow
      biopsy on day +40, showing the presence of erythroblastic islands and isolated
      CD61+ immature cells. The patient did not develop GVHD but died on day +56 from
      idiopathic interstitial pneumonia and multiorgan failure. To our knowledge, this
      is one of the first case reports of unrelated mismatched CB transplantation in an
      adult.

PMID- 8864466
TI  - Unusual split chimaerism after mismatched T-depleted BMT.
AB  - We report a case of haploidentical T-depleted BMT that engrafted durably after a
      highly immunosuppressive conditioning regimen. DNA polymorphism analysis showed
      that granulocytes and monocytes were donor type but T and B lymphocytes were host
      derived. Host tolerance to donor antigens was documented. The patient suffered
      from serious recurrent CMV infections until split chimaerism shifted to full
      donor type 2 years post-BMT. Seven years after BMT the patient remains in
      complete remission.

PMID- 8864468
TI  - Transmission of Plasmodium falciparum by allogeneic bone marrow transplantation.
AB  - We describe a case of Plasmodium falciparum infection in a Comorian patient
      undergoing BMT. The patient's last visit to an endemic area was 1 year prior to
      BMT. The donor left the Comoro Islands 2 months before marrow harvesting. They
      had both had previous episodes of malaria and were seropositive for Plasmodium
      falciparum. At the time of BMT, blood smears were negative in both the donor and
      recipient. On day 12 post-BMT the patient was asymptomatic but a blood smear
      revealed 12.5% parasitemia. We consider that donors and recipients at risk pre
      BMT should routinely be given specific treatment before marrow harvesting and
      conditioning, independent of the appearance of blood smears.

PMID- 8864469
TI  - In vivo CAMPATH-1 followed by T cell-depleted bone marrow transplantation: a
      potential new mode of therapy for hepatitis-associated severe aplastic anemia
      (SAA).
AB  - Bone marrow transplantation (BMT) has been previously reported as a successful
      mode of treatment for hepatitis B and associated severe aplastic anemia (SAA).
      Non-A, non-B, non-C hepatitis is one of the causes of SAA. The etiology of SAA
      caused by non-A, non-B, non-C hepatitis is unknown. There is evidence that the
      immune response and, specifically, T cells and monocytes have a major role in
      both HCV- and HBV-induced liver damage. The liver damage caused by non-A, non-B,
      non-C hepatitis may be associated with similar mechanisms. We describe an 8-year
      old girl who developed SAA post-non-A, non-B, non-C hepatitis infection. She was
      treated by in vivo CAMPATH-1G antibodies followed by T cell depleted HLA-matched
      BMT and cyclosporin A, resulting in gradual improvement and almost normalization
      of liver function. We suggest that treatment with CAMPATH-1G followed by T cell
      depleted BMT and cyclosporin A could be a novel mode of therapy for viral non-A,
      non-B, non-C hepatitis-induced liver damage and associated SAA.

PMID- 8864470
TI  - Myocardial infarction following allogeneic bone marrow transplantation.

PMID- 8864471
TI  - Low-dose interleukin-2 therapy is not associated with cutaneous toxicity after
      autologous transplantation.

PMID- 8864472
TI  - Prolonged thrombocytopenia after administration of granulocyte colony-stimulating
      factor and leukapheresis in a donor for allogeneic peripheral blood stem cell
      transplantation.

PMID- 8864473
TI  - Topical mesalazine in the treatment of chemotherapy and radiotherapy-induced oral
      mucositis.

PMID- 8864474
TI  - Pancreatitis following allogeneic bone marrow transplantation in a patient with
      aplastic anemia.

PMID- 8864475
TI  - Somatostatin 1-12 immunoreactivity is decreased in the hypothalamic lateral
      tuberal nucleus of Huntington's disease patients.
AB  - The hypothalamic lateral tuberal nucleus (NTL) can be recognized in man and
      higher primates, only. The function of this nucleus is unknown, but the NTL is
      affected in a variety of human neurodegenerative diseases, including Huntington's
      disease (HD) and Alzheimer's disease. In the present study we demonstrate an
      abundant presence of somatostatin 1-12 (SST1-12) immunoreactivity in both
      neurites and perikarya of the NTL. This immunoreactivity could be visualized best
      after microwave pretreatment. In HD brains, NTL SST1-12 immunoreactivity was
      greatly reduced, providing further evidence of the presence of SST1-12 as an
      intrinsic neuropeptide in the NTL. Although striatal SST neurons escape
      destruction in HD, our study demonstrates that not all SST neurons are resistant
      to the degenerative process in this disease.

PMID- 8864476
TI  - Perinatal cocaine reduces responsiveness to cocaine and causes alterations in
      exploratory behavior and visual discrimination in young-adult rats.
AB  - Lister hooded female rats were exposed to either saline or cocaine (20 mg/kg
      s.c.) from gestational day 10 every other day until weaning (postnatal day 25).
      The effects of maternal cocaine exposure on novelty-induced exploration and on
      spontaneous and cocaine-induced motor activity were evaluated in young-adult male
      offspring (4 weeks after weaning). Rats exposed to cocaine during development
      spent less time exploring two novel objects. Lack of habituation upon the second
      presentation of the objects and failure in the ability to discriminate between
      the novel and familiar object were also found in cocaine exposed offspring.
      Moreover, maternal cocaine treatment did not affect spontaneous motor activity
      (active time, average speed and rearing) in rats subjected to an open field test.
      Furthermore, perinatal exposure to cocaine significantly attenuated acute cocaine
      (15 mg/kg i.p.)-induced hyperactivity. These data indicate that developmental
      exposure to cocaine, at dose levels below those producing gross malformations
      and/or overt signs of neurotoxicity, causes behavioral changes characterized by
      an altered responsiveness to environmental and pharmacological challenges.

PMID- 8864477
TI  - Microinfusion of corticotropin-releasing factor into the locus
      coeruleus/subcoeruleus nuclei inhibits gastric acid secretion via spinal pathways
      in the rat.
AB  - Brain corticotropin-releasing factor (CRF) is involved in stress-related
      alterations of gastric acid secretion. CRF in the locus coeruleus has been shown
      to induce anxiogenic behavioral responses and to mimic stress-induced alterations
      of colonic motor function. Whether the locus coeruleus/subcoeruleus nucleus
      (LC/SC) is a site of action for CRF to alter gastric acid secretion was
      investigated in urethane-anesthetized gastric fistula rats. In sham-operated
      animals, CRF (126-420 pmol) microinfused bilaterally into the LC/SC induced a
      dose-dependent inhibition of pentagastrin (PG)-stimulated gastric acid secretion
      of 60-81% within the first hour after microinjection. At the 420 pmol dose, this
      inhibitory effect of CRF into the LC/SC lasted throughout the whole observation
      period of 120 min. After bilateral vagotomy, basal and PG-stimulated gastric acid
      secretion at microinjection of vehicle was reduced. Nevertheless, microinfusion
      of 420 pmol CRF into the LC/SC still inhibited significantly gastric acid
      secretion by 62.1%. In contrast, in spinal cord transected animals bilateral
      microinfusion of 420 pmol CRF into the LC/SC did not reduce PG-stimulated gastric
      acid secretion. These data indicate that CRF acts in the LC/SC to induce a long
      lasting inhibition of peripherally stimulated gastric acid secretion via spinal
      pathways. These findings suggest a possible role of the LC/SC in the regulation
      of gastric secretion and of endogenous CRF at these sites in the stress-related
      inhibition of gastric acid secretion by affecting autonomic nervous system
      activity.

PMID- 8864478
TI  - Chronic alcohol reduces calcium signaling elicited by glutamate receptor
      stimulation in developing cerebellar neurons.
AB  - The effect of chronic alcohol (33 mM ethanol) on Ca2+ signals elicited by
      glutamate receptor agonists (quisqualate and NMDA) was examined in developing
      cerebellar Purkinje and granule neurons in culture. The neurons were exposed to
      alcohol during the second week in culture, the main period of morphological and
      physiological development. The Ca2+ signals were measured with fura-2 based
      microscopic video imaging. Chronic exposure to alcohol during development
      significantly reduced the peak amplitude of the Ca2+ signals to quisqualate (1
      microM; Quis) in both the somatic and dendritic regions of the Purkinje neurons.
      The dendritic region was affected to a greater extent than the somatic region.
      Granule neurons also showed a reduced somatic Ca2+ signal to Quis (dendrites not
      measured) in the alcohol-treated cultures, indicating that the effect was not
      limited to Purkinje neurons. In addition to the effects on in the response to
      Quis, the peak amplitude of the Ca2+ signals to NMDA (100 microM) was reduced by
      chronic alcohol exposure during development in both the cultured Purkinje and
      granule neurons. Resting Ca2+ levels were not consistently affected by alcohol
      treatment in either neuronal type. These results indicate that Ca2+ signaling
      linked to glutamate receptor activation is an important target of alcohol in the
      developing nervous system and could be a contributing factor in the altered CNS
      function and development observed in animal models of fetal alcohol syndrome.

PMID- 8864479
TI  - Regulation of glutamate release via NMDA and 5-HT1A receptors in guinea pig
      dentate gyrus.
AB  - The regulation by 5-HT1A and N-methyl-D-aspartate (NMDA) receptors on the
      endogenous glutamate release was investigated in slices of guinea pig dentate
      gyrus. The release of glutamate was increased dose-dependently by the 5-HT1A
      receptor antagonist, NAN-190 at 0.01 to 300 nM, but was not affected by the 5
      HT1A receptor agonist, 8-OH-DPAT even at 100 nM. The release of glutamate evoked
      by 0.1 microM NAN-190 was Ca(2+)-dependent, tetrodotoxin-sensitive and inhibited
      significantly by 8-OH-DPAT at 1, 10 and 100 nM. These results suggest that the 5
      HT1A receptor, which is located postsynaptically on glutamatergic neurons, is
      involved in the inhibitory regulation of glutamate release. The release of
      glutamate evoked by 200 microM NMDA from dentate gyrus was inhibited
      significantly by pretreatment with 8-OH-DPAT at 1, 10 and 100 nM. The release of
      glutamate evoked by 0.1 microM NAN-190 was inhibited significantly by
      pretreatment with MK-801 at 1 and 10 microM, a selective non-competitive NMDA
      receptor antagonist. The release of glutamate evoked by NMDA at 25 and 75 microM
      from dentate gyrus was augmented by the concurrent application of 1 nM NAN-190.
      We propose that the glutamate release from guinea pig dentate gyrus is regulated
      both by the postsynaptic 5-HT1A receptor in an inhibitory manner and by the NMDA
      receptor in a stimulatory manner.

PMID- 8864480
TI  - 5-Hydroxytryptamine (5-HT) agonists: effects on neocortical slow wave activity
      after combined muscarinic and serotonergic blockade.
AB  - In freely-moving rats treated with a combination of reserpine (10 mg/kg, i.p.)
      and scopolamine (5 mg/kg, i.p.), neocortical low voltage fast activity (LVFA)
      associated with continuous multiunit activity (MUA) was abolished and replaced by
      2-6 Hz large irregular slow activity (LISA) above 1.5 mV associated with a burst
      suppression pattern of MUA. Administration of the monoamine oxidase inhibitor
      pargyline (50-100 mg/kg, i.p.) completely suppressed 2-6 Hz LISA and restored
      normal-appearing LVFA and continuous MUA. The 5-hydroxytryptamine (5-HT) receptor
      agonists quipazine (0.5-20 mg/kg, i.p.), (+/-)-DOI (0.1-5 mg/kg, s.c.), and
      buspirone (0.1-10 mg/kg, i.p.), but not 8-hydroxy-2-(di-n-propylamine) tetraline
      (8-OH-DPAT, 0.05-0.8 mg/kg, s.c.) and RU 24969 (1-30 mg/kg, i.p.), produced a
      partial suppression of 2-6 Hz LISA and restored some lower voltage activity (< 1
      mV) above 6 Hz associated with continuous MUA. However, as opposed to pargyline,
      no receptor agonist tested restored continuous, normal-appearing LVFA. Even
      though agonists at 5-HT receptors can produce some activation of neocortical slow
      wave activity after combined cholinergic and serotonergic blockade, this effect
      is not equivalent to that observed after restoration of endogenous 5-HT
      transmission.

PMID- 8864481
TI  - Effect of chronic dexfenfluramine on Fos in rat brain.
AB  - The acute appetite suppressant effect of dexfenfluramine (DF) in rats, which may
      depend upon its action to release serotonin (5-HT) in the brain, often declines
      with repeated dosing (tolerance). The mechanisms of this tolerance remain
      unclear. Previously, we used Fos-like immunoreactivity (Fos-IR) to map potential
      brain sites activated by single injections of DF in rats. A dose of 5 mg DF/kg
      activated the central amygdala (CeA), bed nucleus of the stria terminalis (BST),
      caudate-putamen (CPu), lateral parabrachial nucleus (LPB), nucleus tractus
      solitarius (NST), frontal cerebral cortex and the parvocellular paraventricular
      hypothalamic nucleus (PVN). We now report studies using Fos-IR in an attempt to
      understand which regions might underlie tolerance to the action of DF.
      Pretreatment of rats with an escalating dosage regimen of DF (0.5-4 mg/kg, i.p.)
      was associated with complete loss of Fos-IR to a probe dose (5 mg DF/kg) in the
      cortex, CPu, PVN and NTS, and partial loss of Fos-IR in the BST, CeA and LPB.
      Second, repeated treatment with DF (2 mg/kg), which has been shown to produce
      tolerance the anorexia caused by DF but not cholecystokinin (CCK), likewise
      reduced Fos-IR induced in the above brain regions, but had no effect on Fos-IR
      induced by either CCK or the 5-HT agonist, 5-carboxamidotryptamine. Third,
      repeated treatment with 5-HT (2 mg/kg, s.c.) had no effect on Fos-IR induced by a
      probe dose of DF. These data show that regionally heterogeneous
      hyporesponsiveness to the induction of Fos by DF develops after repeated low
      doses of DF; however, the Fos response to other putative anorectics or weight
      reducing agents is not affected. This may be related to behavioral tolerance.

PMID- 8864482
TI  - Atrophy of cholinergic basal forebrain neurons following excitotoxic cortical
      lesions is reversed by intravenous administration of an NGF conjugate.
AB  - Nerve growth factor (NGF) has been shown to sustain the viability and modulate
      the function of cholinergic basal forebrain neurons. However, under normal
      circumstances, NGF does not cross the blood-brain barrier (BBB) following
      systemic administration making this neurotrophin unavailable to NGF-responsive
      neurons within the central nervous system (CNS). Recently, a non-invasive method
      for delivering NGF to the brain was established in which NGF was conjugated to an
      antibody directed against the transferrin receptor (OX-26) [15, 16]. This
      conjugation facilitates the transfer of NGF from the systemic circulation to the
      CNS via the transferrin transport system. In the present study, we tested whether
      intravenous administration of an OX-26-NGF conjugate could reverse the atrophy of
      cholinergic basal forebrain neurons following removal of the target sites.
      Lesions of the left cerebral cortex were created by epidural application of N
      methyl-D-aspartic acid (NMDA). Seventy-five days later, cholinergic nucleus
      basalis neurons were atrophic ipsilateral to the lesion relative to the
      contralateral side in control rats receiving intravenous injections of vehicle or
      a non-conjugated mixture of OX-26 and NGF. In contrast, intravenous injections of
      the OX-26-NGF conjugate restored the size of nucleus basalis perikarya to within
      normal limits relative to the unlesioned contralateral side. Immunohistochemical
      studies using rat serum albumen antisera indicated that the BBB was closed at the
      time of treatment indicating that this trophic effect did not result from NGF
      crossing through a compromised BBB at the site of the lesion. These data
      demonstrate that systemic administration of a neurotrophic factor-antibody
      conjugate, intended to circumvent the BBB, can provide trophic influences to
      degenerating cholinergic basal forebrain neurons. These data support the emerging
      concept that the conjugate method can facilitate the transfer of impermeable
      therapeutic compounds across the BBB.

PMID- 8864483
TI  - Extracellular Mg2+ modulates intracellular Ca2+ in acutely isolated hippocampal
      CA1 pyramidal cells of the guinea-pig.
AB  - Using digital imaging microscopy and fluorescent probes, isolated hippocampal CA1
      pyramidal neurons of the guinea-pig were used to examine the roles of [Mg2+]o in
      regulation of [Ca2+]i and [Mg2+]i. Low extracellular Mg ([Mg2+]o) (0.3 mM)
      significantly increased [Ca2+]i compared to 1.2 and 4.8 mM [Mg2+]o. In contrast,
      [Mg2+]i levels remained relatively constant, irrespective of alterations of
      [Mg2+]o. The sustained rise in [Ca2+]i induced by low [Mg2+]o was reduced 70% by
      1 microM verapamil and 42% by 1 mM Ni2+, and completely abolished by 5 mM Ni2+.
      The data suggest that [Mg2+]o regulates [Ca2+]i in hippocampal neurons, probably
      by modulating Ca2+ entry via voltage-sensitive Ca2+ channels, which may play
      important roles in epileptogenesis, memory, learning and brain trauma.
      Furthermore, the results demonstrate that intracellular Mg2+ concentration does
      not follow passively the concentration of Mg2+ in the extracellular solution.

PMID- 8864484
TI  - Induction of locomotor activity by the glutamate antagonist DNQX injected into
      the ventral tegmental area.
AB  - DNQX, an antagonist of AMPA/kainate receptors, was injected into the ventral
      tegmental area (VTA) to test the hypothesis that AMPA/kainate receptors in this
      brain region might be involved in regulation of locomotor activity. Bilateral
      injection of 1 microgram DNQX into the VTA increased locomotor activity. In
      addition, unilateral injection of DNQX into this site produced contraversive
      turning, which was potentiated by coadministration of amphetamine (1 mg/kg,
      i.p.). These results suggest that a glutamatergic afferent to the VTA is
      tonically active in inhibiting locomotor activity. The locomotor stimulation
      produced by DNQX was not associated with a change in DOPAC/DA level in the
      nucleus accumbens or the striatum. However, the locomotor stimulation produced by
      DNQX was markedly attenuated following blockade of dopaminergic receptors by
      haloperidol (0.5 mg/kg, s.c.) or following dopamine depletion induced by
      reserpine plus alpha-methyl-para-tyrosine pretreatment. These results suggest
      that a basal activation of dopaminergic receptors is required for expression of
      the locomotor activity elicited by DNQX.

PMID- 8864485
TI  - PCP and ketamine inhibit non-NMDA glutamate receptor mediated hsp70 induction.
AB  - The physiological model for glutamate receptor mediated excitotoxicity entails
      elevation of intraneuronal calcium levels. Excessive activation of the NMDA
      receptor leads to excitotoxicity by prolonged calcium influx via its calcium
      channel. The purpose of this research was to examine the mechanism of non-NMDA
      glutamate receptor mediated excitotoxicity. Mammalian AMPA receptors do not show
      significant calcium conductance. However, some kainate receptors show significant
      calcium conductance. The hypothesis of this research states that non-NMDA
      glutamate agonists (quisqualate (5 microliters of 2 mg/ml i.c.v.), AMPA (4
      microliters of 1 mg/ml i.c.v.), and kainate (15 mg/kg i.p.)) produce significant
      heat shock gene, hsp70, induction via glutamate release with subsequent opening
      of the NMDA receptor calcium channel. PCP (phencyclidine) and ketamine are
      noncompetitive blockers of the NMDA calcium channel. They act to prevent
      significant NMDA receptor excitotoxicity. PCP (20 mg/kg i.p.) and ketamine (60
      mg/kg i.p.) both diminished quisqualate and AMPA hsp70 induction in the CA1, CA2,
      CA3 areas of the hippocampus, in the polymorph area of the dentate gyrus, and in
      the parietal neocortex. PCP significantly (P < 0.05) diminished kainate hsp70
      induction only in the CA1 area and the neocortex. Ketamine failed to reduce
      kainate hsp70 induction. AMPA receptors appear to result in excitotoxic damage
      via glutamate release. Glutamate opens NMDA receptor calcium channels which
      increases intraneuronal calcium levels. Kainate receptors probably mediate
      excitotoxicity via direct calcium conductance with glutamate release being
      important in the CA1 area and neocortex.

PMID- 8864486
TI  - Involvement of GABAB receptor systems in action of antidepressants. II: Baclofen
      attenuates the effect of desipramine whereas muscimol has no effect in learned
      helplessness paradigm in rats.
AB  - Involvement of GABAergic systems in action of antidepressants was examined in the
      learned helplessness paradigm in rats. Rats were treated with desipramine,
      baclofen or muscimol for 14 days. On day 14, the rats were subjected to 90
      inescapable shocks. On day 15, the rats received the 40-trial escape test. The
      inescapable shocks induced the subsequent increase in escape failures in the
      escape test. Desipramine dose-dependently improved the increased escape failures
      induced by the inescapable shocks. Baclofen attenuated the escape failures
      improving effect of desipramine, although baclofen had no effects on the
      increased escape failures when it was injected alone. Muscimol at any dose failed
      to influence the increased escape failures. Therefore, it is suggested that the
      long-term decrease in GABAB neurotransmission may be involved in the action of
      antidepressants. Our present results do not support the hypothesis that
      activation of GABAA receptors may contribute to the action of antidepressants.

PMID- 8864487
TI  - c-Fos expression in the rat intergeniculate leaflet: photic regulation, co
      localization with Fos-B, and cellular identification.
AB  - Ambient light alters the level of the transcriptional regulatory protein c-Fos in
      the suprachiasmatic nucleus, the site of an endogenous circadian clock in
      mammals, and in one other retino-recipient area, the intergeniculate leaflet of
      the lateral geniculate complex. Complementing previous work by ourselves and
      others on the photic and temporal regulation of c-Fos expression in the
      suprachiasmatic nucleus, the present studies investigated c-Fos regulation in the
      rat intergeniculate leaflet, revealing some important differences between the two
      brain regions. In the intergeniculate leaflet, the levels of c-fos mRNA (by in
      situ hybridization) and immunoreactive c-Fos protein (by immunohistochemistry)
      were elevated by light pulses administered either during the subjective day or
      subjective night. The regulation of immunoreactive Fos-B protein was similar to c
      Fos, and 98% of Fos-B-expressing cells were also c-Fos-positive (by double-label
      immunofluorescence). By combining c-Fos immunofluorescence with stereotaxic
      injections of the retrograde tract tracer FluoroGold, we found photically-induced
      c-Fos in 15% of intergeniculate leaflet neurons projecting to the suprachiasmatic
      nucleus and in 34% of those projecting to the contralateral intergeniculate
      leaflet. Intergeniculate leaflet cells that express c-Fos after photic
      stimulation appear to represent a functionally-defined population that does not
      correspond to anatomically-defined categories based on connectivity or
      peptidergic phenotype.

PMID- 8864488
TI  - The effects of N-methyl-D-aspartate (NMDA) and its competitive antagonist, 3-(2
      carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP), injected into caudate
      putamen on kindled amygdaloid seizures in rats.
AB  - N-methyl-D-aspartate (NMDA) is an agonist of NMDA receptors and 3-(2
      carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) is an NMDA receptor
      antagonist. NMDA (1 or 2 nmol per side) or CPP (2.5 or 10 nmol per side) was
      injected into the bilateral caudate-putamen of amygdaloid-kindled rats. In
      addition, CPP (10 nmol) was ipsilaterally or contralaterally injected into the
      unilateral caudate-putamen. Either 20 min after NMDA or 60 min after CPP, the
      kindled amygdala was stimulated at the generalized seizure triggering threshold.
      In a few animals tested, injection of NMDA into the bilateral caudate-putamen
      produced transient spiking activity, with no clinical manifestations. This
      feature began about 5 min after the injection and lasted about 10 s. When these
      animals were excluded from the statistical analysis, NMDA in the caudate-putamen
      showed a weak and non-significant anticonvulsant action. Injection of CPP into
      the bilateral caudate-putamen caused no ictal change, but markedly suppressed the
      kindled seizures. Injection of CPP into the unilateral caudate-putamen,
      regardless of the site, did not cause any ictal change, or affect the stimulation
      of the amygdala. These findings suggest that: (1) NMDA receptors in the caudate
      putamen facilitate the development of kindled amygdaloid seizures; (2) activation
      of NMDA receptors in the bilateral, but not in the unilateral, caudate-putamen is
      required for the generalization and expression of kindled amygdaloid seizures.

PMID- 8864489
TI  - Subdiaphragmatic vagotomy inhibits intra-abdominal interleukin-1 beta stimulation
      of adrenocorticotropin secretion.
AB  - Although interleukin (IL)-1 beta activates the hypothalamic-pituitary-adrenal
      (HPA) axis, the mechanisms by which peripheral IL-1 beta acutely stimulates
      adrenocorticotropin (ACTH) secretion are not clear. Recently, the vagus has been
      implicated in mediating peripheral cytokine signalling of the brain. To
      investigate a possible central mechanism for peripheral cytokine stimulation of
      the HPA axis, we tested the hypothesis that the vagus mediates IL-1 beta
      activation of the HPA axis by an intra-abdominal stimulus. We studied the effect
      of subdiaphragmatic vagotomy on plasma ACTH stimulation in rats by
      intraperitoneal (i.p.) IL-1 beta. Adult male Sprague-Dawley rats underwent
      subdiaphragmatic vagotomy or sham surgery 1 week prior to study. Rats were killed
      1 and 2 h after i.p. saline (control) and low- (4 micrograms/kg) and high-dose
      (20 micrograms/kg) IL-1 beta. Vagotomy markedly attenuated plasma ACTH secretion
      at 2 h after high-dose IL-1 beta stimulation and abolished plasma ACTH secretion
      at 2 h after low-dose IL-1 beta stimulation. At 1 h after low-dose IL-1 beta,
      stimulation of plasma ACTH in vagotomized animals was also markedly diminished
      compared to sham animals. However, vagotomy did not alter stimulation of plasma
      corticosterone at 1 or 2 h after low-dose IL-1 beta or at 2 h after high-dose IL
      1 beta. In addition, vagotomy did not alter stimulation of plasma ACTH or
      corticosterone secretion by insulin-induced hypoglycemia. We conclude that: (1)
      the vagus plays an important role in stimulation of ACTH secretion by intra
      abdominal (i.p.) IL-1 beta; (2) stimulation of corticosterone secretion by i.p.
      IL-1 beta is not altered by vagotomy; and (3) the inhibitory effect of vagotomy
      on activation of the HPA axis appears to be specific for immune stimulation by
      cytokines.

PMID- 8864490
TI  - Endogenous endothelin-1 initiates astrocytic growth after spinal cord injury.
AB  - We developed a rat spinal cord injury model and investigated whether endogenous
      endothelin (ET)-1 plays a role in astrocytic growth after injury.
      Immunohistochemical study showed that the number of immature astrocytes (ACs)
      exhibiting strong reactivity to the monoclonal antibody, RC1, markedly increased
      24 h after the injury. Injection of a potent nonselective ET receptor antagonist,
      SB209670, into the lesion sites significantly inhibited the appearance of RC1
      positive cells 24 h after the injury. In conjunction with this result, the
      increase in immunostaining density of 5-bromo-2'-deoxyuridine in the spinal cord
      24 h after the injury was inhibited by the injection of SB209670. The tissue
      content of ET-1-LI was significantly increased 12 and 24 h after the injury.
      These results suggest that endogenous ET-1 is involved in astrocytic growth after
      spinal cord injury.

PMID- 8864491
TI  - Effect of corticosterone on serotonin and catecholamine receptors and uptake
      sites in rat frontal cortex.
AB  - The effects of corticosterone (1 mg/kg per day for 7 days) on serotonin 5-HT1A, 5
      HT2A, 5-HT uptake sites, and alpha 2-adrenergic receptor sites were measured.
      Corticosterone treatment significantly decreased the number of 5-HT1A receptor
      sites (Bmax = 108 +/- 8.20 fmol/mg protein and 152.31 +/- 13.36 fmol/mg protein
      in corticosterone- and vehicle-treated rats, respectively). No significant
      differences were found in other measures. It is possible that corticosteroids
      exert some of their behavioral effects via regulation of 5-HT1A sites in frontal
      cortex.

PMID- 8864492
TI  - Identification of nasal epithelial cells with carbonic anhydrase activity.
AB  - Although carbonic anhydrase (CA) plays an important role in respiration, there is
      little information about CA in the respiratory system except for the lung. We
      examined the entire nasal cavity of guinea pig to identify CA activity using an
      enzyme-histochemical method. CA activity was detected in a group of
      morphologically distinct nasal epithelial cells. These cells were singly and
      sparsely distributed mainly in the olfactory epithelium and their number
      increased rostrocaudally. These cells were also detected in the apical portion of
      the nasal turbinate, particularly on the nasal endoturbinate, with a more
      complicated structure, rather than on the nasal septum and the roof of nasal
      cavity. Although the physiological role of these cells in unknown, based on the
      morphological and histochemical characteristics and the distribution of these
      cells, we speculated that they may represent a specialized chemoreceptors.

PMID- 8864493
TI  - Evidence that excitatory amino acids mediate afferent input to the primate
      somatosensory thalamus.
AB  - Neurons in and posterior to the primate sensory nucleus of the thalamus (VPL)
      were tested for excitation by iontophoretically applied excitatory amino acid
      agonists. In addition, in several cells the effects of iontophoretically applied
      excitatory amino acid antagonists on the responses to cutaneous stimuli were
      examined. All neurons showed responses to all agonists. The responses of several
      neurons to cutaneous stimuli were attenuated or blocked by local administration
      of receptor antagonists. These results provide initial evidence that
      somatosensory responses of neurons in the primate thalamus are mediated by
      excitatory amino acids.

PMID- 8864494
TI  - Effects of bromocriptine and/or L-DOPA on neurons in substantia nigra of MPTP
      treated C57BL/6 mice.
AB  - The effects of bromocriptine and/or L-DOPA on substantia nigra neurons of MPTP
      intoxicated mice were investigated. L-DOPA reduced the number of neurons.
      Bromocriptine protected the neurons from damage by L-DOPA but had no effect on
      the neurons damaged by MPTP. The treatment of bromocriptine and L-DOPA protected
      the neurons compared with single administration of bromocriptine. It seems
      reasonable to suppose that bromocriptine should be added to L-DOPA in order to
      protect the neurons in parkinsonism.

PMID- 8864495
TI  - Compartmental organization of styloglossus and hyoglossus motoneurons in the
      hypoglossal nucleus of the rat.
AB  - Surgical techniques were used to isolate the extrinsic bellies of the
      styloglossus and hyoglossus muscles from the body of the tongue for cholera toxin
      HRP injection. An average of 53 styloglossus and 121 hyoglossus motoneurons in
      the dorsal subdivision of the hypoglossal nucleus were demonstrated using
      tetramethyl benzidine histochemistry. Styloglossus motoneurons were restricted to
      the rostral 25% of the nucleus while hyoglossus motoneurons occupied other
      regions of the dorsal nucleus.

PMID- 8864496
TI  - Cutaneous blood flow increases in the rat hindpaw during dorsal column
      stimulation.
AB  - The purpose of this study was to determine the optimal stimulation site and
      parameters that result in the greatest changes in cutaneous blood flow during
      dorsal column stimulation (DCS). Laser Doppler flowmetry was used to assess
      cutaneous blood flow changes in both rat hindpaws during DCS with a unipolar ball
      electrode. We found that stimulating the dorsal column at the L2 spinal segment
      at 0.6 mA at either 25 or 50 Hz with a pulse duration of 0.2 ms resulted in the
      largest cutaneous blood flow increases in the rat hindpaw. In addition, the DCS
      response appeared to be limited primarily to the hindpaw ipsilateral to the site
      of DCS.

PMID- 8864497
TI  - Posterior circulation aneurysms.

PMID- 8864498
TI  - The surgical management of patients with glomus tumours of the skull base.
AB  - Total surgical excision is the only treatment modality that offers a cure for
      patients with glomus tumours of the skull base. The vascularity, inaccessibility
      and frequently extensive local spread, all contribute to the difficulties
      encountered in the management of patients with these complex lesions. Owing to
      the rarity of skull base glomus tumours, experience in their management can only
      be attained over long periods of time. We describe the surgical management of 20
      patients with large glomus tumours of the skull base treated by an
      otoneurosurgical team over an 11-year period. Overall, 70% of patients had an
      excellent outcome, 10% a good outcome and 20% a poor outcome at a mean follow-up
      of 3.1 years. Poor outcomes were due to severe facial nerve palsies in two cases,
      and poorly accommodated palsies of the bulbar cranial nerves in a further two
      patients. The management of postoperative neurological deficits is discussed in
      detail. We conclude that in the majority of patients with skull base glomus
      tumours, complete surgical excision can be safely achieved.

PMID- 8864499
TI  - Anterior callosotomy for intractable epilepsy: outcome in a series of twenty
      patients.
AB  - This series reports 20 patients with intractable epilepsy who underwent corpus
      callosotomy during the period 1984-1993. The mean age of patients at the time of
      onset of seizures was 9 years and at the time of callosotomy 26 years. The
      seizure types were generalized tonic-clonic (18/20), drop attacks (13/20),
      absences (12/20) and complex partial seizures (8/20). The most common
      electroencephalographic (EEG) abnormalities were 'bilateral multiple spike and
      wave' (7/20), or 'generalized/multifocal spike and slow wave' (7/20). The follow
      up was 5.6 (SD 0.6) years. Six patients have remained free of major generalized
      motor seizures and 10 additional patients experienced significant sustained
      reduction in the severity and frequency of the seizures. In total, 16 of 20
      patients (80%) had a favourable outcome. The type of seizures associated with the
      most improved outcome were drop attacks, and generalized tonic-clonic seizures,
      in 11/13 and 14/18 of the patients, respectively. No relationship was established
      between seizure control and preoperative EEG patterns, computed tomography or
      magnetic resonance imaging findings. The most frequent complication was transient
      mild left hemiparesis that occurred in four patients. The mortality was nil. This
      study confirms the efficacy of corpus callosum division as a surgical option for
      selected patients with medically intractable epilepsy. In addition, results
      suggest that the history and clinical classification of the seizures have
      prognostic value as selection criteria for patients referred for this operation.

PMID- 8864500
TI  - Cerebral venous oxygen saturation monitoring: is dominant jugular bulb
      cannulation good enough?
AB  - Venous oxygen saturation at the clinically dominant jugular bulb (SjO2) and that
      at the confluence of the cerebral sinuses (SccsO2) were compared by direct
      simultaneous blood sampling of 13 severely head injured patients. The side of
      dominant jugular bulb (JB) was determined by neck compression test. The right
      side was chosen if the test was equivocal. In effect, the right side was
      cannulated in all cases. Subsequent angiography showed that two of the 13 cases
      were left side dominant. In all, 176 pairs of blood samples were analysed.
      Correspondence rates (the difference between each pair of blood samples being
      less than 4% of oxygen saturation) for individual case were good (80-100%) in
      nine cases including one case with left side dominance. Correspondence rates were
      moderate in two cases (50 and 56%); the differences were not clinically
      significant. In the remaining two cases, including one with left side dominance,
      the correspondence rates were poor (0 and 4%, respectively); SccsO2 was always
      lower than SjO2; median differences were 13.4 and 23.1%. Ischemia in the cerebral
      hemispheres would have been underestimated if management were based on SjO2.
      Monitoring at the dominant JB accurately reflected the global and hemispheric
      cerebral oxygenation in 11/13 of cases. Monitoring at the non-dominant JB is not
      recommended.

PMID- 8864501
TI  - Cerebellar astrocytoma: report of 13 cases aged over 20 years and review of the
      literature.
AB  - Cerebellar astrocytoma in adulthood is a distinct neoplasm with a variable
      prognosis. We reviewed retrospectively 13 cases in patients aged 21 years or
      over, seen between 1976 and 1992. These accounted for 19% of all cases of
      cerebellar astrocytoma seen during that period. The tumour was located in the
      midline in six patients and laterally in seven; seven patients were females and
      six were males. The low grade tumours had an overall favourable course, similar
      to that seen in cerebellar astrocytoma in childhood, with follow-up ranging from
      4 to 10 years. The poorly differentiated form, seen in four of the cases, showed
      progression or recurrence within 4-24 months, regardless of the extent of removal
      or post-operative radiation therapy.

PMID- 8864502
TI  - Surgery for patients with central protruded lumbar discs who have failed
      conservative therapy.
AB  - The clinical presentation and results of surgery of patients with central
      protruded lumbar discs have not been well defined or distinguished from studies
      of patients with lateral herniated discs. Many patients are denied surgical
      treatment, even though they are incapacitated by pain, because they do not have
      the classic radiographic findings seen in patients with lateral disc herniation.
      Sixty-three symptomatic patients with radiographically documented central lumbar
      disc protrusion were analysed. All patients had failed at least 6 months of
      conservative therapy. Although lumbar spinal pain was the most common complaint,
      24 patients also presented with bilateral leg pain and 33 with unilateral leg
      pain; 26 had unilateral limitation of straight leg raising. An interesting
      observation was that unilateral symptoms and dural tension signs can be seen in
      patients with central disc protrusion. After surgical follow-up for a mean of 51
      months, 86% achieved good results when analysed by the Prolo Functional Economic
      Outcome Rating Scale. It is postulated that pain is mediated by neuropeptides and
      arachidonic acid degradation products which are a response to mechanical annular
      injury.

PMID- 8864503
TI  - Infra-red thermographic evaluation of spinal cord electrostimulation in patients
      with chronic pain after failed back surgery.
AB  - This study sought to visualize spinal-cord stimulation activity by infra-red
      thermography in humans suffering from chronic lumbosciatic pain. All the patients
      had previously undergone neurosurgery for a herniated intervertebral disc.
      Temperature changes were evaluated in two defined body areas after starting,
      stopping, maintaining or not starting the stimulation. In one body area,
      corresponding to the pain location, the patient experienced stimulation
      paraesthesia, whereas in the non-painful (second) area no stimulation
      paraesthesia were present. The patients were studied on four consecutive days
      with a randomly chosen stimulation pattern. Temperature changes in identical and
      comparable skin areas were measured and statistically analysed. No statistically
      significant temperature variation was found between the painful and non-painful
      areas. These findings do not confirm the idea that spinal cord stimulation
      induces vasodilation in the affected pain area when stimulation is present. Infra
      red thermography is not able to differentiate the stimulated from the non
      stimulated areas.

PMID- 8864504
TI  - Choroid plexus arteriovenous malformations. A report of four pathologically
      proven cases and review of the literature.
AB  - The clinical, radiological and pathological findings of four cases of primary
      intraventricular haemorrhage secondary to choroid plexus arteriovenous
      malformations (AVM) are described and the relevant literature reviewed. In three
      of the cases the diagnosis was confirmed or made at autopsy. The fourth case
      survived to undergo craniotomy followed by radiosurgery with excellent results.
      All AVMs originated in the choroid plexus of the lateral ventricle, and autopsy
      confirmation required a high degree of suspicion and the systematic microscopic
      examination of serial coronal sections of the ventricle with the clot in situ.

PMID- 8864505
TI  - Basal ganglia-internal capsule low density lesions in children with mild head
      injury.
AB  - I report my experience with 14 children with mild head injury who presented with
      a distinct clinico-radiological syndrome. Twelve of these children were less than
      18 months of age. A fall was the most common mode of injury. These children
      presented with immediate onset of hemiparesis. CT showed a low density lesion in
      the region of the basal ganglia-internal capsule. All these children made a good
      recovery within 2 weeks. The pathogenesis of this particular clinico-radiological
      syndrome is discussed.

PMID- 8864506
TI  - Endoscopy-assisted burr hole evacuation of subdural empyema.
AB  - A 71-year-old man developed a large multi-loculated subdural empyema following
      the evacuation of a chronic subdural haematoma. The pockets of pus were
      successfully evacuated endoscopically via the burr holes resulting in good
      recovery and no re-accumulation. The advantages of this technique and the
      difficulties encountered during this procedure are discussed.

PMID- 8864507
TI  - Tuberculous osteitis of the skull: a case report and review of the literature.
AB  - A 13-year-old girl of Pakistani origin presented with a non-tender, fluctuant
      swelling over her left parietal area and an underlying skull defect. At the apex
      of the swelling there was a sinus. Cultures of the discharge were positive for
      Mycobacterium tuberculosis. We present a case report of tuberculosis of the skull
      and review of the literature. We highlight the difficulty which still exists in
      establishing a diagnosis of tuberculosis in countries where it is uncommon.

PMID- 8864508
TI  - Isolated injury to a major branch of the posterior interosseous nerve of the
      forearm with surgical repair.
AB  - We report the case of a patient who sustained an isolated injury to one of the
      two main branches of the posterior interosseous nerve of the forearm. Repair by
      epineurial suture was followed by complete recovery.

PMID- 8864509
TI  - Unattached intracranial extra-axial schwannoma.
AB  - We describe an intracranial extra-axial petroclival schwannoma which did not
      arise from any cranial nerve, nor was it attached to brain parenchyma or dura.
      The possible pathogenesis is discussed.

PMID- 8864510
TI  - Regression of syringomyelia after removal of a posterior fossa epidermoid tumour.
AB  - The case is reported of a 49-year-old man with a giant infratentorial extradural
      epidermoid tumour, with cervical syringomyelia and hydrocephalus, and partial
      protrusion of the cerebellar tonsils through the foramen magnum. The patient
      complained of symptoms of raised intracranial pressure and was admitted to our
      Department, where ventriculoperitoneal shunting and total removal of the
      epidermoid tumour were performed. One year later, MR imaging demonstrated
      collapse of the cervical syringomyelia.

PMID- 8864511
TI  - Cervical spondylotic myelopathy with syringomyelia.
AB  - Syringomyelia may complicate cervical spondylotic myelopathy (CSM). We describe a
      case of CSM with instability at C3/4 and a cervicothoracic syrinx which was
      demonstrated using magnetic resonance imaging. Decompression and stabilization,
      without drainage of the syrinx, were adequate surgical treatment.

PMID- 8864512
TI  - Extrusion of BOP-B graft orally following anterior cervical discectomy and
      fusion.
AB  - Graft extrusion following anterior cervical discectomy and fusion is a recognized
      complication. We report a case of oral extrusion of a synthetic graft (BOP B,
      Biocompatible Orthopaedic Polymer).

PMID- 8864514
TI  - Origin of germ cell tumours.

PMID- 8864513
TI  - Sigmoidoscopic neurosurgery? Treatment of an unusual complication of
      ventriculoperitoneal shunting.
AB  - A 16-year-old male with acute hydrocephalus due to bilateral acoustic neuromata
      was treated successfully with a ventriculoperitoneal shunt before formal neuroma
      resection. However, 2 years postoperatively, he noticed the distal shunt per
      rectum while defaecating. Subsequent removal was successfully performed using a
      flexible sigmoidoscope.

PMID- 8864515
TI  - Cavernous haemangiomas in the cavernous sinus.

PMID- 8864516
TI  - EndothelinB (ETB) receptor-activated potentiation of cholinergic nerve-mediated
      contraction in human bronchus.
AB  - In human isolated bronchial preparations, the endothelinB (ETB) receptor
      selective agonist, sarafotoxin S6c (Stx6c; 1 nM) increased nerve-mediated
      contraction in response to electrical field stimulation (EFS) at 0.5-1 Hz from 19
      +/- 4% to 42 +/- 7% (n = 9). This effect was blocked in the presence of the ETB
      receptor-selective antagonist, BQ-788 (10 microM). These data are consistent with
      findings in some animal species that ET-1 and related peptides have marked
      neuromodulatory influences on the cholinergic system. Furthermore, they provide
      additional support for the concept that ET-1 may have a mediator role in
      bronchial obstruction in asthma.

PMID- 8864517
TI  - Inhibitory action of nociceptin on spinal dorsal horn neurones of the rat, in
      vivo.
AB  - Intrathecally administered nociceptin (5, 50, 225 micrograms) dose-relatedly
      inhibited the C-fibre evoked wind-up and post-discharge of dorsal horn neurones,
      but not the baseline C-fibre evoked responses. Spinal naloxone 50 micrograms, but
      not 10 micrograms, reversed the effects of nociceptin. Thus the antinociceptive
      role of nociceptin in the spinal cord differs from that of classical opioids.

PMID- 8864518
TI  - Evidence for P-glycoprotein-modulated penetration of morphine-6-glucuronide into
      brain capillary endothelium.
AB  - 1. Morphine-6-glucuronide is one of the major metabolites of morphine. The potent
      analgesic action of this compound together with its potential lower apparent
      toxicity in man, when compared with morphine, indicated its clinical importance.
      2. Primary cultures of porcine brain capillary endothelial cells were used to
      study brain penetration of morphine-6-glucuronide. Biochemical characterization
      of the cell cultures revealed a marked enrichment in enzymatic activity of
      alkaline phosphatase (56 fold) and angiotensin converting enzyme (230 fold) as
      compared to whole brain tissue. By immunostaining the presence of vimentin,
      factor VIII, the tight junction associated protein ZO-1, and P-glycoprotein was
      shown. Functional characterization revealed that the carrier system responsible
      for transport of neutral amino acids was intact. 3. Uptake and transport of
      morphine-6-glucuronide was marginal and in the range of the extracellular marker
      sucrose. However, uptake of morphine-6-glucuronide was enhanced significantly (P
      < 0.0001) in presence of the inhibitors of P-glycoprotein, verapamil or
      vincristine. The finding that morphine-6-glucuronide may serve as a substrate for
      P-glycoprotein was confirmed in multidrug-resistant P388 tumour cells. 4. We
      conclude that penetration of the blood-brain barrier by morphine-6-glucuronide
      may depend on the expression of the product of the multidrug-resistance (MDR)
      gene in brain capillary endothelial cells.

PMID- 8864519
TI  - Modulation by atrial natriuretic factor of receptor-mediated cyclic AMP-dependent
      responses in canine pulmonary artery during heart failure.
AB  - 1. Pacing-induced congestive heart failure (CHF) in dogs is associated with
      increased plasma levels of atrial natriuretic factor (ANF) and inhibition of
      receptor-mediated cyclic AMP-dependent relaxation in isolated pulmonary arteries
      (PA). Since ANF is known to be negatively coupled to adenylate cyclase, we
      studied cyclic AMP-mediated relaxation to isoprenaline (Iso) and arachidonic acid
      (AA) in PA from control dogs (C), dogs with pacing-induced CHF (CHF) and dogs
      with bilateral atrial appendectomy and CHF (ATR APP+CHF). 2. In CHF, plasma ANF
      levels increased from a baseline of 80 +/- 8 pg ml-1 to 283 +/- 64 pg ml-1 (P <
      0.05), but the ATR APP+CHF group failed to show this increase (67 +/- 7 pg ml-1
      vs 94 +/- 15 pg ml-1, P = NS). Plasma ANF levels, however, did not influence
      myocardial dysfunction in CHF. 3. The relaxation of 49 +/- 5% to 1 microM Iso in
      C was reduced to 23 +/- 4% in CHF (P < 0.05), but relaxation of 49 +/- 12% was
      observed in the ATR APP+CHF group (P = NS vs C). Relaxation responses to 10
      microM AA were as follows: 77 +/- 5% (C, n = 8), 27 +/- 8% (CHF, n = 10, P < 0.05
      vs C), and 93 +/- 5% (ATR APP+CHF, n = 5). The presence of CHF, or the plasma ANF
      levels, did not affect responses to cyclic GMP-mediated relaxing agents in PA. 4.
      These data indicate that the myocardial performance in CHF is not influenced by
      plasma ANF levels. However, altered cyclic AMP-mediated relaxation in PA during
      CHF is, in part, modulated by circulating ANF levels.

PMID- 8864520
TI  - The cardiovascular and renal functional responses to the 5-HT1A receptor agonist
      flesinoxan in two rat models of hypertension.
AB  - 1. This study investigated the importance of renal sympathetic nerves in
      regulating sodium and water excretion from the kidneys of stroke prone
      spontaneously hypertensive and 2K1C Goldblatt hypertensive rats anaesthetized
      with chloralose/urethane (17.5/300 mg initially and supplemented at regular
      intervals), and prepared for measurement of renal function. 2. In stroke prone
      spontaneously hypertensive rats, flesinoxan, 30-1000 micrograms kg-1, i.v.,
      caused graded reductions in blood pressure and heart rate of 74 +/- 5 mmHg and 63
      +/- 9 beats min-1, respectively at the highest dose (P < 0.001). Renal blood flow
      did not change at any dose of drug while glomerular filtration rate fell by some
      20% (P < 0.001) at the highest dose of drug, absolute and fractional sodium
      excretions, approximately doubled at 100 micrograms kg-1, and thereafter fell to
      below the baseline level at 1000 micrograms kg-1. 3. This pattern of excretory
      response was abolished following acute renal denervation when flesinoxan caused
      dose-related reductions in urine flow and sodium excretion, similar to that
      obtained by a mechanical reduction of renal perfusion pressure. 4. Flesinoxan
      administration (30-1000 micrograms kg-1, i.v.) into 2K1C Goldblatt hypertensive
      rats caused a maximum decrease in blood pressure and heart rate (both P < 0.001)
      of 34 +/- 3 mmHg and 20 +/- 6 beats min-1 and while renal blood flow and
      glomerular filtration rate were autoregulated, from 160 to 125 mmHg, there were
      dose-related decreases in urine volume and sodium excretion from the clipped and
      non-clipped kidneys of approximately 50-60% at the highest dose. 5. These
      findings suggest that in the stroke prone spontaneously hypertensive rat the
      renal nerves importantly control sodium and water reabsorption at the level of
      the tubules, whereas in 2K1C Goldblatt hypertensive rats, they play a minor role.

PMID- 8864521
TI  - The effect of the calcium-antagonist nitrendipine on intracellular calcium
      concentration in endothelial cells.
AB  - 1. Nitrendipine induces NO-release from coronary vascular endothelium presumably
      by activating endothelial NO-synthase. We have investigated whether this effect
      may be mediated by an influence on the intracellular calcium in endothelial
      cells. 2. Bovine aortic endothelial cells (BAEC) were incubated with Fura-2/AM (1
      microM) for 30 min and Fura-2 fluorescence was measured at 510 nm in response to
      chopped excitation with both 340 and 380 nm. The ratio 340/380 nm (known to
      reflect changes in intracellular calcium) was calculated from these data. 3.
      Nitrendipine (0.1 to 100 microM) led to a significant, concentration-dependent,
      monophasic increase in [Ca2+]i in suspended BAEC by 11 +/- 2 nM (0.1 microM), 23
      +/- 3 nM (1 microM), 34 +/- 4 nM (10 microM) and by 47 +/- 5 nM (100 microM) from
      a control levels of 118 +/- 10 nM. 4. This elevation of intracellular calcium was
      prevented by pretreatment of BAECs with gadolinium (100 microM) or by incubation
      with calcium free saline solution. In contrast, the application of 0.3 microM
      thapsigargin did not abolish the nitrendipine-induced calcium signal. In
      additional experiments it was shown that the nitrendipine-induced NO-release (as
      measured with the oxy-haemoglobin-method could also be inhibited by gadolinium
      and was absent in calcium-free solution. 5. Thus, nitrendipine elevates
      intracellular calcium in suspended BAECs in a concentration-dependent manner.
      This elevation is mainly due to a gadolinium-sensitive calcium influx from the
      extracellular space rather than a calcium release from intracellular stores.

PMID- 8864522
TI  - Effect of Hoe 694, a novel Na(+)-H+ exchange inhibitor, on intracellular pH
      regulation in the guinea-pig ventricular myocyte.
AB  - 1. Hoe 694 (3-methylsulphonyl-4-piperidinobenzoyl, guanidine hydrochloride) is a
      Na+/H+ exchange (NHE) inhibitor exhibiting cardioprotective properties during
      ischaemia and reperfusion in animal hearts. We have (i) tested the selectivity of
      Hoe 694 for NHE over other pHi-regulating mechanisms in the myocardium, and (ii)
      tested if the functionally important NHE isoform contributing to intracellular pH
      regulation in heart is NHE-1, as suggested from molecular biology studies of this
      protein. 2. pHi was recorded by fluorescence microscopy with carboxy SNARF-1, AM
      loaded into single ventricular myocytes of guinea-pig. 3. In nominally HCO3-free
      media, recovery of pHi from an intracellular acid load is mediated by NHE, and
      was inhibited by Hoe 694, amiloride (an NHE inhibitor) or dimethyl amiloride
      (DMA, a high affinity NHE inhibitor) with potency values of 2.05, 87.3 and 1.96
      microM respectively, giving the potency series: Hoe 694 congruent to DMA > >
      amiloride. This potency series, and the potency values (corrected for drug
      competition with extracellular Na+) match those determined previously for cloned
      NHE-1 expressed in mutant fibroblasts. In the absence of extracellular Na+ (to
      inhibit NHE), Hoe 694 had no effect on pHi. 4. In 5% CO2/HCO3(-)-buffered
      solution containing DMA, pHi recovery from acidosis is mediated by Na(+)-HCO3-
      symport and was unaffected by Hoe 694. The drug also had no effect on pHi
      recovery from an alkali-load, a process largely mediated by Cl(-)-HCO3- exchange.
      Finally, the fall of pHi upon adding extracellular Na-lactate is assisted by H(+)
      lactate symport, and this too was unaffected by Hoe 694. 5. We conclude (i) Hoe
      694 has no detectable inhibitory potency for pH-regulating carriers in heart
      other than NHE. (ii) native NHE functioning during pHi-regulation in the
      cardiomyocyte is the NHE-1 isoform. These data strengthen the case for NHE-1
      being the receptor for mediating the cardioprotective effects of Hoe 694.

PMID- 8864523
TI  - Effect of opiates on transmitter release from visualized hypogastric boutons
      innervating the rat pelvic ganglia.
AB  - 1. The effect of opiates on neurotransmission between visualized hypogastric
      nerve boutons and postganglionic cell bodies has been examined using
      extracellular recording of nerve bouton impulses (NBIs) and excitatory
      postsynaptic currents (e.p.s.cs). 2. Morphine (10 to 40 microM) did not affect
      neurotransmission in the ganglia. Dynorphin-A (4 microM) and U50488H (1 microM)
      decreased quantal transmitter release and naloxone (10 microM) reversed these
      effects. 3. Morphine (10 microM), dynorphin-A (4 microM) and U50488H (1 microM)
      did not affect either the time course or consistency with which the NBI was
      recorded. 4. Dynorphin-A (1 to 4 microM) and U50488H (1 microM) decreased the
      average amplitude of e.p.s.cs by increasing the number of failures to release
      quanta from single or small groups of 2 to 4 boutons during continuous nerve
      stimulation at 0.1 Hz. 5. The decrease in quantal release induced by dynorphin-A
      and U50488H in 0.2 to 0.5 mM [Ca2+]zero was readily reversed by increasing the
      extracellular calcium ion concentration to 1 mM. 6. It was concluded that kappa
      opioid receptors are located on the boutons of the hypogastric nerve and when
      activated by kappa-opioid receptor agonists reduce quantal release without
      affecting the NBI.

PMID- 8864524
TI  - The role of TNF-alpha in fever: opposing actions of human and murine TNF-alpha
      and interactions with IL-beta in the rat.
AB  - 1. The role of tumour necrosis factor-alpha (TNF-alpha) in fever is
      controversial. Some studies have indicated that TNF-alpha acts as a cryogen to
      inhibit fever, while others suggest that TNF-alpha is an endogenous pyrogen which
      mediates fever. The majority of studies in experimental animals supporting a
      cryogenic action have been conducted using human (h)TNF-alpha, which has been
      shown to bind only to one (p55) of the two TNF-alpha receptors in rodents. 2. The
      aim of the present investigation was to study the role of TNF-alpha in fever by
      comparing effects of hTNF-alpha, which binds only to the p55 receptor, with those
      of murine (m) TNF-alpha, which binds to both p55 and p75 TNF-alpha receptors, and
      to investigate the relationship between TNF-alpha and interleukin-1 (IL-1), an
      important endogenous pyrogen. 3. Injection of hTNF-alpha (0.3-10 micrograms kg-1,
      i.p.) had no effect on core temperature in conscious rats (measured by remote
      radiotelemetry), whereas mTNF-alpha (3 micrograms kg-1) induced fever which was
      maximal 1 h after the injection (38.2 +/- 0.2 degrees C compared to 37.3 +/- 0.1
      degrees C in controls). Intracerebroventricular (i.c.v.) administration of either
      form of TNF-alpha elicited dose-dependent fever at doses higher than 0.12
      microgram kg-1. 4. Peripheral injection of hIL-1 beta (1 microgram kg-1) resulted
      in fever (38.3 +/- 0.2 degree C compared to 37.2 +/- 0.1 degrees C in controls at
      2 h), which was significantly attenuated (P < 0.01) by co-administration of a sub
      pyrogenic dose of hTNF-alpha (1 microgram kg-1), but was unaffected by co
      administration of mTNF-alpha (0.1 or 0.3 microgram kg-1, i.p.). In contrast,
      intracerebroventricular (i.c.v.) co-administration of a sub-pyrogenic dose (0.12
      microgram kg-1) of hTNF-alpha did not attenuate fever induced by intraperitoneal
      (i.p.) injection of IL-1 beta, and sub-pyrogenic dose (0.12 microgram kg-1,
      i.c.v.) of mTNF-alpha significantly prolonged the febrile response to IL-1 beta.
      Pretreatment of animals with anti-TNF-alpha antiserum (i.c.v.) did not affect the
      febrile response to systemic IL-1 beta. 5. Animals injected i.p. with a pyrogenic
      dose of mTNF-alpha developed fever (38.2 +/- 0.2 degrees C compared to 37.3 +/-
      0.1 degrees C in controls 2 h after the injection) that was completely abolished
      by peripheral administration of IL-1ra (2 mg kg-1, P < 0.001), while i.c.v.
      administration of IL-1ra (400 micrograms/rat) did not affect mTNF-alpha-induced
      fever. 6. These data indicate that endogenous TNF-alpha is probably a pyrogen and
      that previous results suggesting cryogenic actions of TNF-alpha resulted from the
      use of a heterologous protein in the rat. The markedly contrasting effects of
      mTNF-alpha and TNF-alpha could result from different interactions with the two
      TNF-alpha receptor subtypes. The data also suggest that fever induced by
      exogenous TNF-alpha is mediated via release of IL-1 beta in peripheral tissues,
      but not in the brain.

PMID- 8864525
TI  - The role of endogenous bradykinin in blood pressure homeostasis in spontaneously
      hypertensive rats.
AB  - 1. The role of endogenous bradykinin in mean arterial blood pressure (BP)
      homeostasis was studied in spontaneously hypertensive (SHR) and normotensive
      (WKY) rats by the use of a bradykinin B2-receptor antagonist (BKant; Hoe 140,
      11.6 micrograms kg-1) and converting enzyme (kininase II) inhibitor (captopril,
      10 mg). To obtain a response to captopril that was induced through inhibition of
      kinin-degradation only and not through inhibition of angiotensin II-formation,
      the studies were performed on binephrectomized male rats to eliminate the renin
      angiotensin system. 2. The role of the nitric oxide (NO) and the adrenergic
      systems were evaluated by the use of NO-synthase inhibitor (L-NAME, 0.3 g kg-1)
      and phentolamine (2 mg kg-1), respectively. 3. The rats were anaesthetized and
      pretreated with two injections of vehicle (PBS) or drugs spaced 5 min apart: PBS
      + PBS; BKant + PBS; PBS + L-NAME; BKant + L-NAME; or phentolamine + L-NAME. All
      rats were given captopril 15 min later. Time-control groups were treated with L
      NAME but not captopril. 4. In WKY rats, captopril did not significantly alter BP
      in any of the groups. In the SHR-PBS + PBS group, on the other hand, captopril
      induced an immediate fall in BP (delta BP = -23 +/- 4 mmHg, P < 0.0017) which was
      completely blocked by BKant (delta BP = 2 +/- 2 mmHg) (P < 0.0011). L-NAME did
      not significantly alter the immediate hypotensive response to captopril but
      disclosed a later hypertensive reaction. In L-NAME + BKant-treated rats, both the
      hypotensive response and the late hypertension was abolished. In rats treated
      with phentolamine + L-NAME, the immediate fall in BP was not different from the
      controls whereas the late hypertension was absent. 5. BKant itself had no effect
      on basal BP in either WKY or SHR even when a 10 times higher dose was tested in a
      separate set of experiments. This was true also for conscious, nonnephrectomized
      SHR rats. 6. It was concluded that endogenous production of bradykinin was
      demonstrable through kininase II-inhibition in hypertensive but not in
      normotensive rats. However, this endogenous bradykinin did not play a role in
      basal BP homeostasis. The captopril-induced hypotension depended on kinin but,
      under the present conditions, not on NO as a mediator. The fall in BP induced a
      compensatory adrenergic hypertensive response which was revealed when the
      continuous NO-synthesis was blocked by L-NAME.

PMID- 8864526
TI  - Investigation of the contributions of nitric oxide and prostaglandins to the
      actions of endothelins and sarafotoxin 6c in rat isolated perfused lungs.
AB  - 1. The aims of the study were to assess the contribution of prostaglandins and
      nitric oxide (NO) to the effects of endothelin (ETs) and sarafotoxin 6c (SX6c) in
      perfused rat lungs. This was carried out by using indomethacin, a cyclo-oxygenase
      inhibitor and NG-nitro-L-arginine (L-NOARG), a NO synthase inhibitor. Responses
      were studied under basal perfusion conditions and in other experiments after the
      elevation of vascular tone with the thromboxane-mimetic, U46619. The sub-types of
      ET receptors involved were characterized by use of ET receptor antagonists and
      cross-tachyphylaxis. 2. Pulmonary perfusion pressure (PPP), lung weight and
      pulmonary inflation pressure (PIP), were continuously recorded. Although L-NOARG
      (100 microM) did not alter basal parameters it markedly augmented the
      vasoconstriction and lung weight increases induced by ET-1 (50-400 pmol) or SX6C
      (25-200 pmol) while vasoconstrictor responses to phenylephrine were not affected
      by L-NOARG. 3. L-NOARG markedly potentiated the bronchoconstriction induced by ET
      1 or SX6C whereas it had no effect on responses to carbachol. 4. When vascular
      tone was elevated, low doses (1.25-40 pmol) of ET-1, ET-3 and SX6C produced falls
      in PPP. The vasodilator potencies were SX6C > ET-1 = ET-3. The ETA receptor
      antagonist, BQ123, did not affect these depressor responses whereas the mixed
      ETA/ETB antagonist, bosentan, blocked them. 5. Indomethacin (10 microM) partially
      inhibited vasodilator response to ET-1, whereas it had no effect on SX6C-induced
      vasodilation. 6. L-NOARG plus indomethacin completely blocked ET-1 induced
      vasodilation, whereas responses to SX6C were blocked by L-NOARG alone. 7.
      Repeated injections of submaximal doses of ET-1 or SX6C caused tachyphylaxis to
      vasodilator responses. Subsequent injections of SX6C or ET-1 did not elicit
      depressor responses showing cross tachyphylaxis had occurred. 8. These findings
      indicate that under basal conditions the pulmonary vasoconstrictor, lung weight
      and bronchoconstrictor responses to ET-1 and SX6C are attenuated by evoked
      release of nitric oxide (NO). When vascular tone was elevated, lower doses of ETs
      and SX6C produced vasodilatation. These vasodilator responses are indirect, those
      to SX6C being mediated via NO production, whereas those to ET-1 involve both NO
      and prostanoid(s). Tachyphylaxis and ET antagonist experiments indicate that the
      same receptor subtype is involved in mediating the vasodilatation and that this
      is of the ETB type located on the endothelium. However the post-receptor
      vasodilator events triggered by ET-1 or SX6C appear to be different.

PMID- 8864527
TI  - Effects of RP 73401, a novel, potent and selective phosphodiesterase type 4
      inhibitor, on contractility of human, isolated bronchial muscle.
AB  - 1. The aim of this study was to investigate the smooth muscle relaxant effects of
      the novel, selective phosphodiesterase (PDE) type 4 inhibitor, RP 73401 in
      comparison with the classical PDE 4 inhibitor, rolipram, the non-selective PDE
      inhibitor, theophylline and the beta-adrenoceptor agonist, isoprenaline on the
      human, isolated bronchus. 2. At resting tone, the rank order of potency (pD2) for
      the relaxants was RP 73401 > or = rolipram > or = isoprenaline >> theophylline.
      In terms of maximum relaxation produced (Emax) the PDE 4-selective inhibitors
      were similar, but the maximal effects (70-75% of theophylline, 3 mM) were lower
      than that observed with isoprenaline (98% of theophylline, 3 mM) or theophylline
      itself (100%). 3. On the human isolated bronchus pre-contracted with
      acetylcholine (ACh, 0.1 or 1.0 mM), the rank order of potency remained the same.
      The maximal responses to RP 73401 and rolipram were however markedly reduced
      (Emax 39.9-46.6%) compared with isoprenaline (Emax 79-85%). 4. In tissues pre
      contracted with ACh (0.1 mM), RP 73401 and rolipram (10(-9)-10(-7) M)
      significantly and concentration-dependently increased tissue sensitivity to
      isoprenaline. RP 73401 and rolipram were similar in potency. Both selective PDE 4
      inhibitors also significantly increased the maximal relaxant effects of
      isoprenaline. These effects were not observed with the PDE 3 inhibitor,
      siguazodan. 5. In terms of retention by tissues (an index of duration of action),
      the onset of action of RP 73401 (2.11 +/- 0.53 min) and rolipram (1.70 +/- 0.45
      min) was significantly slower than that of isoprenaline (0.33 +/- 0.06 min) or
      theophylline (1.17 +/- 0.25 min). The retention of RP 73401 (89.0 +/- 21.9 min)
      on the human isolated bronchial tissues after washing was however dramatically
      longer than that of rolipram (18.3 +/- 4.5 min), theophylline (3.43 +/- 0.58 min)
      or isoprenaline (2.81 +/- 0.31 min). 6. These data indicate that RP 73401 is a
      potent and long acting relaxant of human bronchial muscle in vitro. RP 73401 is
      more potent than the classical PDE 4-selective inhibitor rolipram and the non
      selective PDE inhibitor theophylline and is retained in bronchial tissue for a
      much longer period of time.

PMID- 8864528
TI  - Identification of cyclic AMP phosphodiesterases 3, 4 and 7 in human CD4+ and CD8+
      T-lymphocytes: role in regulating proliferation and the biosynthesis of
      interleukin-2.
AB  - 1. The cyclic AMP phosphodiesterases (PDE) expressed by CD4+ and CD8+ T
      lymphocytes purified from the peripheral blood of normal adult subjects were
      identified and characterized, and their role in modulating proliferation and the
      biosynthesis of interleukin (IL)-2 and interferon (IFN)-gamma evaluated. 2. In
      lysates prepared from both subsets, SK&F 95654 (PDE3 inhibitor) and rolipram
      (PDE4 inhibitor) suppressed cyclic AMP hydrolysis indicating the presence of PDE3
      and PDE4 isoenzymes in these cells. Differential centrifugation and subsequent
      inhibitor and kinetic studies revealed that the particulate fraction contained,
      predominantly, a PDE3 isoenzyme. In contrast, the soluble fraction contained a
      PDE4 (approximately 65% of total activity) and, in addition, a novel enzyme that
      had the kinetic characteristics of the recently identified PDE7. 3. Reverse
      transcription-polymerase chain reaction (RT-PCR) studies with primer pairs
      designed to recognise unique sequences in the human PDE4 and PDE7 genes amplified
      cDNA fragments that corresponded to the predicted sizes of HSPDE4A, HSPDE4B,
      HSPDE54D and HSPDE7. No message was detected for HSPDE4C after 35 cycles of
      amplification. 4. Functionally, rolipram inhibited phytohaemagglutinin- (PHA) and
      anti-CD3-induced proliferation of CD4+ and CD8+ T-lymphocytes, and the
      elaboration of IL-2, which was associated with a three to four fold increase in
      cyclic AMP mass. In all experiments, however, rolipram was approximately 60 fold
      more potent at suppressing IL-2 synthesis than at inhibiting mitogenesis. In
      contrast, SK&F 95654 failed to suppress proliferation and cytokine generation,
      and did not elevate the cyclic AMP content in T-cells. Although inactive alone,
      SK&F 95654 potentiated the ability of rolipram to suppress PHA- and anti-CD3
      induced T-cell proliferation, and PHA-induced IL-2 release. 5. When a combination
      of phorbol myristate acetate (PMA) and ionomycin were used as a co-mitogen,
      rolipram did not affect proliferation but, paradoxically, suppressed IL-2 release
      indicating that cyclic AMP can inhibit mitogenesis by acting at, or proximal to,
      the level of inositol phospholipid hydrolysis. 6. Collectively, these data
      suggest that PDE3 and PDE4 isoenzymes regulate the cyclic AMP content, IL-2
      biosynthesis and proliferation in human CD4+ and CD8+ T-lymphocytes. However, the
      ability of rolipram to suppress markedly mitogen-induced IL-2 generation without
      affecting T-cell proliferation suggests that growth and division of T-lymphocytes
      may be governed by mediators in addition to IL-2. Finally, T-cells have the
      potential to express PDE7, although elucidating the functional role of this
      enzyme must await the development of selective inhibitors.

PMID- 8864529
TI  - Identification of potent P2Y-purinoceptor agonists that are derivatives of
      adenosine 5'-monophosphate.
AB  - 1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate
      were synthesized and tested as agonists for activation of the phospholipase C
      linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase
      linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor
      stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine
      monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems,
      eleven different 2-thioether-substituted adenosine monophosphate analogues were
      full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an
      EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was
      16,000 fold greater than that of ATP and was only 10 fold less than the potency
      of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3.
      Monophosphate analogues that were the most potent activators of the C6 cell P2Y
      purinoceptor were also the most potent activators of the turkey erythrocyte P2Y
      purinoceptor. However, agonists were in general more potent at the C6 cell
      receptor, and potency differences varied between 10 fold and 300 fold between the
      two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate
      were potent P2Y-purinoceptor agonists no effect of these analogues on the human
      P2U-purinoceptor were observed. 5. These results support the view that a single
      monophosphate is sufficient and necessary for full agonist activity at P2Y
      purinoceptors, and provide insight for strategies for development of novel P2Y
      purinoceptor agonists of high potency and selectivity.

PMID- 8864530
TI  - Neural 5-HT4 receptors in the human isolated detrusor muscle: effects of indole,
      benzimidazolone and substituted benzamide agonists and antagonists.
AB  - 1. In strips of human isolated detrusor muscle, the 5-hydroxytryptamine (5-HT)
      receptor (5-HT4) that mediates facilitation of neuromuscular cholinergic
      transmission was further characterized by using 5-HT and a series of ligands
      known for their 5-HT4 agonist (5-methoxytryptamine: 5-MeOT, cisapride, (R,S)
      zacopride, BIMU 8) or antagonist (RS 23597, GR 125487, DAU 6285) properties. 2.
      In the presence of methysergide (1 microM) and ondansetron (3 microM) to isolate
      pharmacologically the 5-HT4 receptors, 5-HT (0.3 nM-1 microM), 5-MeOT (10 nM -30
      microM), BIMU 8 (10 nM-3 microM), cisapride (0.1-10 microM) and (R,S)-zacopride
      (0.1-30 microM) potentiated cholinergic contractions to electrical field
      stimulation in a concentration-dependent manner. RS 23597 (10 nM-10 microM), a
      competitive 5-HT4 receptor antagonist in other systems, also showed agonist
      properties. The following rank order of potency as an agonist was obtained: 5-HT
      (pEC50 = 8.0) > RS 23597 (7.0) = BIMU 8 (6.9) > or = cisapride (6.6) > 5-MeOT
      (6.0) > or = (R,S)-zacopride (5.7). Relative to 5-HT (intrinsic activity = 1), 5
      MeOT acted as a full agonist (1.03), while BIMU 8 (0.76), (R,S)-zacopride (0.61),
      RS 23597 (0.60) and cisapride (0.41) behaved as partial agonists. 3. The
      potentiation by 5-HT was competitively antagonized by the selective 5-HT4
      receptor antagonist GR 125487 (0.3-3 nM) with a pA2 estimate of 9.75 (Schild
      slope of 1.09), and by DAU 6285 (1 microM; pK3 = 6.45). Additionally, GR 125487
      (3 nM) antagonized the responses to 5-MeOT (pKB = 9.72) and reversed the
      potentiation induced by RS 23597. As an antagonist, RS 23597 (10, 30 and 100 nM)
      inhibited the response to 5-HT. In addition, 30 and 100 nM RS 23597 reduced the 5
      HT response maximum by 30 and 50%, respectively. The pKB value calculated at 10
      nM was 8.0. 4. Thus, in the human isolated detrusor muscle, the 5-HT4 receptors
      mediating facilitation of cholinergic neuromuscular transmission are activated by
      indoleamines (5-HT, 5-MeOT), substituted benzamide (cisapride, (R,S)-zacopride),
      benzoate (RS 23597) and benzimidazolone (BIMU 8) derivatives. The activities (in
      terms of both potency and efficacy) of most agonists, as well as the affinity
      estimates of the antagonists GR 125487 and DAU 6285, are comparable to those
      found in other peripheral tissues. Exceptions are RS 23597, which acted either as
      a partial agonist or as an antagonist of the response to 5-HT1 and 5-MeOT that
      showed an unusually low potency. The latter findings may be ascribed to
      differences in the efficiency of receptor coupling mechanisms and/or in the
      molecular structure (i.e. splice variants) of the 5-HT4 receptor.

PMID- 8864531
TI  - Enhancement by calcitonin gene-related peptide of non-contractile Ca2(+)-induced
      nicotinic receptor desensitization at the mouse neuromuscular junction.
AB  - 1. Nicotinic acetylcholine receptor (AChR)-operated non-contractile Ca2+
      mobilization (unaccompanied by muscle contraction) depressed contractile Ca2+
      mobilization (accompanied by muscle contraction) in mouse diaphragm muscles. In
      the process of nicotinic AChR desensitization, the enhancing role of calcitonin
      gene-related peptide (CGRP) on the non-contractile Ca2(+)-induced depression of
      contractile Ca2+ mobilization was investigated by measurement of Ca2(+)-aequorin
      luminescence in the presence of neostigmine (0.1 microM). 2. When the phrenic
      nerve was stimulated with paired pulses at intervals of 150, 300, 600, 1000 and
      2000 ms, contractile Ca2+ transients were elicited during the generation of non
      contractile Ca2+ mobilization. The amplitude of the contractile Ca2 transients
      elicited by the second pulse (S2) was depressed at the shorter pulse intervals,
      but not at the longer pulse intervals. 3. The extent of depression of S2 was
      enhanced when the duration of non-contractile Ca2+ mobilization was prolonged by
      CGRP (10 nM). However, CGRP failed to enhance the depression of S2 when non
      contractile Ca2+ mobilization was not observed at the low external Ca2+
      concentration (1.3 mM). 4. The enhancing effect by CGRP on the depression of S2
      was counteracted by staurosporine (3 nM), a protein kinase-C inhibitor, despite
      prolongation of the duration of non-contractile Ca2+ mobilization. 5. When H-89
      (1 microM), a protein kinase-A inhibitor, completely blocked non-contractile Ca2+
      mobilization, the depression of S2 was diminished. The prolongation of the
      duration of non-contractile Ca2+ mobilization by AA373 (300 microM), a protein
      kinase-A activator, enhanced the depression of S2. The enhancing effect was
      observed neither with CGRP nor with AA373, in the presence of H-89 (0.1 microM).
      6. These findings suggest that the CGRP mobilizes non-contractile Ca2+ through
      activation of protein kinase-A, which in turn may activate protein kinase-C, then
      enhance the desensitization of postsynaptic nicotinic AChRs at the neuromuscular
      junction.

PMID- 8864532
TI  - Effects of intravenous anaesthetic agents on fast inhibitory oscillations in the
      rat hippocampus in vitro.
AB  - 1. General anaesthetic agents prevent awareness of sensory input and subsequent
      recall of sensory events after administration. The mechanisms involved in higher
      sensory processing, including awareness and recall, are not fully elucidated.
      However, fast oscillations in neuronal activity in the 20-80 Hz (gamma) range
      have been strongly implicated. Here we have investigated the effects of two
      anaesthetic agents and a sedative/hypnotic drug on these oscillations. 2. Trains
      of fast oscillations, shown previously to be shaped by gamma-aminobutyric acid
      (GABAA) receptor activation, were evoked by pressure ejection of L-glutamate (10
      nM) onto the perisomatic region of hippocampal area CAI in the presence of 3-((R)
      2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (R-CPP), 50 microM, 6-nitro-7
      sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX), 50 microM and 2-hydroxysaclofen,
      0.2 mM. 3. Thiopentone (10-200 microM) and propofol (0.5-10 microM) dose
      dependently decreased both the maximum oscillation frequency, by approx. 90%, and
      the incidence of evoked rhythmic oscillations by approx. 60%. Diazepam (0.05-1
      microM) decreased maximum oscillation frequency by about 40% but did not affect
      the incidence of evoked oscillations. 4. The similar effects of thiopentone and
      propofol were mediated by both a large (about 600%) increase in the decay
      constant (tau D) of GABAA receptor-mediated inhibitory postsynaptic currents
      (i.p.s.cs) and a bicuculline-sensitive leak current. The two drugs had differing
      effects on i.p.s.c. amplitude. Diazepam caused a small increase in tau D (about
      170%) and did not alter leak currents at the doses used. 5. Effects of the
      anaesthetic agents were seen on the above measurements at similar concentrations
      to those estimated in the CNS during clinical and veterinary anaesthesia. We
      suggest that the effects on fast oscillations associated with cognition may
      contribute to the mechanism by which these agents produce general anaesthesia.

PMID- 8864533
TI  - Development of cholinergic and inhibitory non-adrenergic non-cholinergic
      responses in the rat gastric funds.
AB  - 1. Cholinergic contractions and inhibitory non-adrenergic non-cholinergic (NANC)
      relaxations were studied in longitudinal muscle strips of the gastric funds of 2,
      4 and 8 week old rats. 2. Contractions induced by electrical stimulation of the
      cholinergic neurones and by administration of acetylcholine decreased during
      development. The potentiating effect of physostigmine was similar in the 3 age
      groups. 3. Short train stimulation in NANC conditions induced fast relaxations,
      which were more pronounced in 4 and 8 week than in 2 week old rats. These
      relaxations were almost completely inhibited by NG-nitro-L-arginine methyl ester
      (L-NAME) in the 3 age groups. The nitric oxide-induced relaxations did not change
      during development. 4. Sustained electrical stimulation in NANC conditions
      induced an initial relaxation, which was almost totally blocked by L-NAME,
      followed by an almost complete recovery of tone at lower frequencies of
      stimulation. At higher frequencies of stimulation, the recovery of tone was
      incomplete or absent. This sustained relaxation was only partially reduced by L
      NAME and almost abolished by L-NAME plus alpha-chymotrypsin. The initial
      relaxations increased during development, while the sustained relaxations
      remained similar during this period. Vasoactive intestinal polypeptide-induced
      relaxations were also similar in the 3 age groups. 5. These results show that the
      sensitivity of the gastric fundus to acetylcholine decreases from 2 weeks to 8
      weeks postnatally, while the importance of the nitrergic innervation increases
      during this period.

PMID- 8864534
TI  - Effect of intrarenally infused parathyroid hormone-related protein on renal blood
      flow and glomerular filtration rate in the anaesthetized rat.
AB  - 1. Parathyroid hormone-related protein (PTHrP) is expressed in the kidney and
      acts on vascular PTH/ PTHrP receptors to vasodilate the isolated kidney and to
      stimulate renin release. However, effects of PTHrP on renal blood flow (RBF) and
      glomerular filtration rate (GFR) in vivo have not been assessed in the absence of
      its cardiac, peripheral and central effects. We investigated the renal effects of
      PTH and PTHrP infused into the left renal artery of anaesthetized rats. 2.
      Intrarenal infusions, adjusted to generate increasing concentrations of human
      PTHrP(1-34) and rat PTH(1-34) in renal plasma (2 x 10(-11) to 6 x 10(-9) M)
      produced a comparable dose-dependent increase in RBF. The rise was 4% at the
      lowest and 34% at the highest concentrations of peptides. Up to a concentration
      of 2 x 10(-9) M, mean arterial pressure (MAP) and heart rate were not affected,
      but at 6 x 10(-9) M, intrarenally infused peptides reached the peripheral
      circulation, and caused a fall in MAP within a few minutes. While MAP returned to
      basal value after the last peptide infusion, RBF remained more than 10% above
      control for at least 30 min. 3. Two competitive PTH/PTHrP receptor antagonists,
      [Nle8,18, Tyr34]-bPTH(3-34)amide and [Leu11, D-Trp12]-hPTHrP(7-34)amide (2 x 10(
      8) M) were devoid of agonist activity, but markedly antagonized the dose
      dependent increase in RBF elicited by PTHrP. 4. GFR and urine flow were measured
      in left PTHrP-infused experimental kidney and right control kidney. Renal PTHrP
      concentration of 10(-10) M elevated left RBF by 10%, and GFR by 20% without
      significantly increasing filtration fraction, and increased urine flow by 57%. In
      the right control kidney GFR and diuresis did not change. 5. The results indicate
      that PTHrP has similar renal haemodynamic effects as PTH and increases RBF, GFR
      and diuresis in anaesthetized rats.

PMID- 8864535
TI  - Inhibition by sodium nitroprusside of a calcium store depletion-activated non
      selective cation current in smooth muscle cells of the mouse anococcygeus.
AB  - 1. The effects of sodium nitroprusside (SNP) on the non-selective cation current
      activated in response to intracellular calcium store depletion were studied using
      the whole-cell patch-clamp technique in single smooth muscle cells isolated from
      the mouse anococcygeus. Voltage-dependent calcium currents were blocked with
      extracellular nifedipine, and caesium and tetraethylammonium chloride were used
      to block voltage-dependent potassium currents. Calcium stores were depleted with
      caffeine (10 mM), carbachol (50 microM) or cyclopiazonic acid (CPA 10 microM; an
      inhibitor of the sarcoplasmic reticulum [SR] calcium-ATPase). 2. At a holding
      potential of -40 mV, both CPA and caffeine activated inward currents which
      consisted of two clearly distinguishable components; an initial transient current
      followed by a smaller sustained current. In the case of CPA, the amplitudes of
      the transient and sustained components were 19.7 +/- 2.1 pA and 3.5 +/- 0.3 pA
      respectively, whilst the equivalent values for caffeine were 188 +/- 21 and 4.8
      +/- 0.3 pA. As described previously, the transient current results from
      activation of a calcium-dependent chloride conductance whilst the sustained
      current is a non-selective cation current, activated following intracellular
      calcium store depletion. 3. The muscarinic receptor agonist, carbachol, also
      activated a transient followed by a sustained current with amplitudes of 238 +/-
      55 and 4.7 +/- 0.5 pA respectively. Superimposed on the sustained current were
      regular, oscillations of calcium-activated chloride current. 4. Both the
      transient and the sustained currents activated by CPA were absent in cells
      pretreated with SNP (10 microM). Application of SNP to a cell following
      activation of the sustained current by CPA inhibited the current by 88.6 +/-
      3.8%. SNP (10 microM) did not inhibit the transient current activated by caffeine
      but abolished the sustained current. 5. SNP (10 microM) had no effect on the
      initial transient current activated by carbachol (50 microM). However, it did
      inhibit the oscillations in the inward current. In recordings from cells bathed
      in extracellular solution containing the chloride channel blocker, anthracene-9
      carboxylic acid (A-9-C; 1 mM), carbachol activated only a sustained current. This
      current was inhibited by 88.1 +/- 6.5% by a concomitant application of SNP (10
      microM) and was absent in cells pretreated with the nitrovasodilator. 6. The
      effects of SNP on the currents activated by caffeine (10 mM) were mimicked by 8
      bromo-cyclic GMP (200 microM); thus the nucleotide had no effect on the transient
      current activated by caffeine but abolished the sustained current. The effects of
      SNP, but not those of 8-bromo-cyclic GMP, were inhibited by the nitric oxide
      sensitive guanylyl cyclase inhibitor, 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxaline-1
      one (ODQ; 1 microM). ODQ alone produced a significant increase in the size of the
      sustained current activated by caffeine (7.8 +/- 0.7 pA). 7. These findings
      suggest that SNP activates guanylyl cyclase to inhibit the non-selective cation
      current activated as a result of intracellular calcium store depletion in mouse
      anococcygeus cells. Since the non-selective cation current appears to underlie
      the calcium entry process responsible for maintaining the sustained contractions
      to agonists in this tissue, this action of SNP may represent an important
      mechanism by which nitrates relax non-vascular smooth muscle.

PMID- 8864536
TI  - Impaired activation of adenylyl cyclase in lung of the Basenji-greyhound model of
      airway hyperresponsiveness: decreased numbers of high affinity beta
      adrenoceptors.
AB  - 1. To evaluate mechanisms involved in the impaired beta-adrenoceptor stimulation
      of adenylyl cyclase in tissues from the Basenji-greyhound (BG) dog model of
      airway hyperresponsiveness, we compared agonist and antagonist binding affinity
      of beta-adrenoceptors, beta-adrenoceptor subtypes, percentage of beta
      adrenoceptors sequestered, and coupling of the beta-adrenoceptor to Gs alpha in
      lung membranes from BG and control mongrel dogs. We found that lung membranes
      from the BG dog had higher total numbers of beta-adrenoceptors with a greater
      percentage of receptors of the beta 2 subtype as compared to mongrel lung
      membranes. 2. Agonist and antagonist binding affinity and the percentage of beta
      adrenoceptors sequestered were not different in BG and mongrel dog lung
      membranes. However, the percentage of beta-adrenoceptors in the high affinity
      state for agonist was decreased in BG lung membranes suggesting an uncoupling of
      the receptor from Gs alpha. 3. Impaired coupling between the beta-adrenoceptor
      and G protein documented by the decreased numbers of beta-adrenoceptors in the
      high affinity state in BG lung membranes, is a plausible explanation for the
      reduced stimulation of adenylyl cyclase and the resultant reduction in airway
      smooth muscle relaxation in this model.

PMID- 8864537
TI  - The effect of ovariectomy on depressed contractions to phenylephrine and KCl and
      increased relaxation to acetylcholine in isolated aortic rings of female compared
      to male rabbits.
AB  - 1. Differences in vascular responses to phenylephrine, acetylcholine (ACh) and
      potassium chloride (KCl) were studied in rabbit aorta from female and male
      rabbits, in the absence and presence of an inhibitor of nitric oxide (NO)
      production, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). 2.
      Phenylephrine and KCl-induced contractions, were significantly reduced in
      amplitude (P < 0.01) in the rings from female rabbits compared to those from male
      rabbits. 3. ACh-induced relaxation was greater (P < 0.01) in aortic rings from
      females than from males. 4. Incubation of the rings with L-NAME abolished the
      phenylephrine-induced contraction differences between rings from male and female
      rabbits. 5. Ovariectomy eliminated the differences in vascular responses to
      phenylephrine, KCl and ACh of aortic rings from the female rabbits. 6. Both basal
      and ACh-stimulated release of nitrites from aortic rings was greater (P < 0.01)
      in vascular tissue from female than male rabbits. 7. These results indicate that
      differences in vascular reactivity in aortic rings from male and female rabbits
      may be associated with a higher release of NO, resulting in an increased
      vasodilator response in the female rabbits.

PMID- 8864538
TI  - Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1
      receptors on peripheral sympathetic nerves.
AB  - 1. Activation of CB1 receptors by plant cannabinoids or the endogenous ligand,
      anandamide, causes hypotension via a sympathoinhibitory action in anaesthetized
      rats. In mouse isolated vas deferens, activation of CB1 receptors inhibits the
      electrically evoked twitch response. To determine if these effects are related to
      presynaptic inhibition of noradrenaline (NA) release, we examined the effects of
      delta 9-tetrahydrocannabinol (delta 9-THC), anandamide and the CB1 antagonist,
      SR141716A, on exocytotic NA release in rat isolated atria and vasa deferentia. 2.
      In isolated atria and vasa deferentia preloaded with [3H]-NA, electrical field
      stimulation caused [3H]-NA release, which was abolished by tetrodotoxin 0.5
      microM and concentration-dependently inhibited by delta 9-THC or anandamide, 0.3
      10 microM. The inhibitory effect of delta 9-THC and anandamide was competitively
      antagonized by SR 141716A, 1-10 microM. 3. Tyramine, 1 microM, also induced [3H]
      NA release, which was unaffected by tetrodotoxin, delta 9-THC or anandamide in
      either atria or vasa deferentia. 4. CB1 receptor mRNA is present in the superior
      cervical ganglion, as well as in whole brain, cerebellum, hypothalamus, spleen,
      and vas deferens and absent in medulla oblongata and atria, as demonstrated by
      reverse transcription-polymerase chain reaction. There was no evidence of the
      presence of CB1A receptor mRNA in ganglia, brain, or cerebellum. These results
      suggest that activation of presynaptic CB1 receptors located on peripheral
      sympathetic nerve terminals mediate sympathoinhibitory effects in vitro and in
      vivo.

PMID- 8864539
TI  - Pharmacological modulation of immunoreactive imidazoline receptor proteins in rat
      brain: relationship with non-adrenoceptor [3H]-idazoxan binding sites.
AB  - 1. The densities of various imidazoline receptor proteins (with apparent
      molecular masses of approximately 29/30-45- and 66-kDa) were quantitated by
      immunoblotting in the rat cerebral cortex after various drug treatments. The
      modulation of these imidazoline receptor proteins was then compared with the
      changes in the density of non-adrenoceptor [3H]-idazoxan binding sites (I2-sites)
      induced by the same drug treatments. 2. Chronic treatment (7 days) with the I2
      selective imidazol(in)e drugs idazoxan (10 mg kg-1), cirazoline (1 mg kg-1) and
      LSL 60101 (10 mg kg-1) differentially increased the immunoreactivity of
      imidazoline receptor proteins. The levels of the 29/30-kDa protein were increased
      by idazoxan and LSL 60101 (23%), the levels of the 45-kDa protein only by
      cirazoline (44%) and those of the 66-kDa protein only by idazoxan (50%). These
      drug treatments also increased the density of I2-sites (32-42%). 3. Chronic
      treatment (7 days) with efaroxan (10 mg kg-1), RX821002 (10 mg kg-1) and
      yohimbine (10 mg kg-1), which possess very low affinity for I2-imidazoline
      receptors, did not alter either the immunoreactivity of imidazoline receptor
      proteins or the density of I2-sites. 4. Chronic treatment (7 days) with the
      monoamine oxidase (MAO) inhibitors clorgyline (10 mg kg-1) and phenelzine (10 mg
      kg-1) decreased the immunoreactivity of the 29/30-kDa (17-24%), 45-kDa (19%) and
      66-kDa (23-31%) imidazoline receptor proteins. The alkylating agent N
      ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (1.6 mg kg-1, 6 h) also decreased
      the levels of the three imidazoline receptor proteins (20-47%). These drug
      treatments consistently decreased the density of I2-sites (31-57%). 5.
      Significant correlations were found when the mean percentage changes in
      immunoreactivity of imidazoline receptor proteins were related to the mean
      percentage changes in the density of I2-sites after the various drug treatments
      (r = 0.92 for the 29/30-kDa protein, r = 0.69 for the 45-kDa protein and r = 0.75
      for the 66-kDa protein). 6. In the rat cerebral cortex the I2-imidazoline
      receptor labelled by [3H]-idazoxan is heterogeneous in nature and the related
      imidazoline receptor proteins (29/30-, 45- and 66-kDa) detected by immunoblotting
      contribute differentially to the modulation of I2-sites after drug treatment.

PMID- 8864540
TI  - Photolysis of the novel inotropes EMD 57033 and EMD 57439: evidence that Ca2+
      sensitization and phosphodiesterase inhibition depend upon the same enantiomeric
      site.
AB  - 1. We studied the effects of flash photolysis on the novel enantiomeric cardiac
      inotropes EMD 57033 (a calcium sensitizer) and EMD 57439 (a phosphodiesterase III
      inhibitor) in rat isolated ventricular trabeculae. 2. In skinned trabeculae, EMD
      57439 had no effect on force production, consistent with lack of an active cyclic
      AMP system in this preparation. In contrast, EMD 57033 potentiated force at
      partial and maximal activation. A single flash of near u.v. light given at
      partial activation (30-70%) reduced force potentiation by 52.4 +/- 5.2%. No
      effect was produced by flashes in the presence of EMD 57439 or in the absence of
      either drug. 3. The time course of relaxation induced by EMD 57033 photolysis was
      indistinguishable from that obtained on deactivating the muscle by rapidly
      lowering Ca2+ using photolysis of the caged chelator of calcium, diazo-2. 4. In
      intact, twitching trabeculae, EMD 57033 increased diastolic and peak force and
      slowed relaxation. These effects were simultaneously reduced by a light flash. In
      these muscles EMD 57439 reduced force, without affecting the twitch time course.
      These effects were also reduced by a light flash. 5. The u.v. absorbance spectra
      of EMD 57033 and EMD 57439 were identical. After photolysis optical density
      decreased substantially and the peak shifted from 320 nm to 280 nm. 6. The proton
      n.m.r. spectra of these compounds were identical. The main change post-photolysis
      was a decrease in the proton signal associated with the enantiomeric carbon atom.
      7. This novel manipulation of the molecular structure of EMD 57033 and EMD 57439
      within an experiment thus provides direct evidence linking calcium sensitization
      to a particular molecular structure. The three main effects of the sensitizer on
      the twitch were simultaneously abolished and may be mechanistically linked. Flash
      photolysis may be a useful tool for further investigations of the actions of
      these compounds. In particular, flash photolysis of the sensitizer represents a
      novel method of rapidly deactivating cardiac muscle.

PMID- 8864541
TI  - [3H]-thioperamide as a radioligand for the histamine H3 receptor in rat cerebral
      cortex.
AB  - 1. The purpose of the present study was to characterize the binding of the
      histamine H3 receptor antagonist, [3H]-thioperamide, to rat cerebral cortical
      membranes. 2. The binding of [3H]-thioperamide to rat cerebral cortical membranes
      reached equilibrium after incubation with [3H]-thioperamide after 8-10 h at 4
      degrees C. Equilibrium was maintained for up to 18 h of incubation. Addition of 1
      microM (R)-alpha-methylhistamine rapidly dissociated [3H]-thioperamide from its
      binding sites. From these kinetic experiments a dissociation constant of 0.3 nM
      was obtained for [3H]-thioperamide. 3. Saturation experiments with [3H]
      thioperamide using 1 microM (R)-alpha-methylhistamine to define nonspecific
      binding were best analysed according to a single site model. A dissociation
      constant (KD) of 0.80 +/- 0.06 nM (n = 3) and a maximal number of binding sites
      (Bmax) of 73 +/- 20 fmol mg-1 protein (n = 3) were obtained for the binding of
      [3H]-thioperamide to rat cerebral cortical membranes. 4. Saturation experiments
      with [3H]-thioperamide using 0.3 microM iodophenpropit to define nonspecific
      binding were best analysed according to a two site model. For the high affinity
      [3H]-thioperamide site a KD value of 1.1 +/- 0.3 nM (n = 3) and Bmax value of 162
      +/- 108 fmol mg-1 protein (n = 3) were obtained whereas KD and Bmax values for
      the low affinity site were 96 +/- 19 nM and 4346 +/- 3092 fmol mg-1 protein (n =
      3), respectively. 5. Using 5 nM [3H]-thioperamide, the binding was hardly
      displaced by H3 agonists within concentration-ranges expected to bind to the
      histamine H3 receptor. Under these conditions, [3H]-thioperamide binding was
      fully displaced by various H3-antagonists, yet most H3 antagonists showed Ki
      values different from those expected for the histamine H3 receptor. 6. Using 0.3
      nM [3H]-thioperamide, 50-60% of the total binding was potently displaced by the
      H3 agonists histamine, (R)-alpha-methylhistamine, (S)-alpha-methylhistamine,
      imetit and immepip. Displacement of the binding of 0.3 nM [3H]-thioperamide
      binding exhibited clear stereoselectivity for the R and S isomers of alpha
      methylhistamine. 7. Binding of 0.3 nM [3H]-thioperamide was completely displaced
      by several H3 antagonists (thioperamide, iodophenpropit, iodoproxyfan, and
      burimamide) and biphasic displacement curves were obtained; the Ki values for the
      high affinity site corresponded well with the expected values for the H3
      receptor. Antagonists fully displaced the binding of 5 nM [3H]-thioperamide with
      affinities comparable to the low affinity site found with 0.3 nM [3H]
      thioperamide. 8. Ondansetron and haloperidol did not displace binding of 5 nM
      [3H]-thioperamide at concentrations at which the former are known to bind to 5
      HT3 or sigma receptors, respectively. On the other hand, nonselective cytochrome
      P450 inhibitors displaced the binding of 5 nM [3H]-thioperamide from both rat
      cerebral cortical membranes and rat liver microsomes. 9. It is concluded that the
      histamine H3 antagonist, [3H]-thioperamide, can be used as a radioligand to study
      the histamine H3 receptor in rat brain, provided that subnanomolar concentrations
      are used in displacement studies. Moreover, the specific binding should be
      defined with an H3 agonist, since most H3 antagonists share with [3H]
      thioperamide a low affinity, high density, non-H3 receptor binding site(s) in rat
      brain. The latter is probably due to binding to cytochrome P450 isoenzymes.

PMID- 8864542
TI  - Evidence for the presence of cannabinoid CB1 receptors in mouse urinary bladder.
AB  - 1. CP 55,244, (-)-11-hydroxy-dimethylheptyl-delta 8-tetrahydrocannabinol, WIN
      55,212-2, delta 9-tetrahydrocannabinol, nabilone and anandamide each inhibited
      electrically-evoked contractions of the mouse isolated urinary bladder in a
      concentration-related manner, their EC50 values being respectively 15.9, 18.27,
      27.23, 1327.6, 1341.5 and 4950.3 nM. (+)-11-hydroxy-dimethylheptyl-delta 8
      tetrahydrocannabinol was inactive at the highest concentration used (10 microM).
      2. SR141716A (31.62 or 100 nM) produced parallel rightward shifts in the log
      concentration-response curves of CP 55,244, (-)-11-hydroxy-dimethylheptyl-delta 8
      tetrahydrocannabinol, WIN 55,212-2, delta 9-tetrahydrocannabinol and anandamide
      for inhibition of electrically-evoked bladder contractions. The effect of the
      antagonist on the log concentration-response curve of CP 55,244 was shown to
      depend on the concentration of SR141716A used (31.62 to 1000 nM). 3. The
      amplitudes of contractions evoked by acetylcholine or beta, gamma-methylene-L-ATP
      were not decreased by 316.2 nM CP 55,244 or 3162 nM delta 9-tetrahydrocannabinol.
      Electrically-evoked contractions were almost completely abolished by 200 nM
      tetrodotoxin. 4. The above results support the hypothesis that mouse urinary
      bladder contains prejunctional CB1 cannabinoid receptors which can mediate
      inhibition of electrically-evoked contractions, probably by reducing contractile
      transmitter release. 5. AM 630 which behaves as a cannabinoid receptor antagonist
      in the mouse isolated vas deferens did not antagonize the ability of CP 55,244 or
      delta 9-tetrahydrocannabinol to inhibit electrically-evoked contractions of the
      mouse bladder. 6. SR141716A produced small but significant increases in the
      amplitude of electrically-evoked contractions of the bladder suggesting that this
      tissue may release an endogenous cannabinoid receptor agonist or that some
      cannabinoid receptors in this tissue are precoupled to the effector system.

PMID- 8864543
TI  - Tachykininergic synaptic transmission in the coeliac ganglion of the guinea-pig.
AB  - 1. The responses of coeliac ganglion neurones of the guinea-pig to electrical
      stimulation of the mesenteric nerves and applications of tachykinin receptor
      agonists were investigated by use of intracellular recording techniques. 2.
      Ganglion neurones were classified into three groups based on firing patterns in
      response to a depolarizing current pulse: phasic (38% of the population), tonic
      (39%) and atypical (23%). In the majority of phasic neurones (91%) a long after
      hyperpolarization (LAH) lasting 5-8 s followed action potentials induced by a
      train of depolarizing current pulses. In contrast, LAH was rarely observed in
      tonic neurones (5%). 3. In most of tonic neurones (90%) slow excitatory post
      synaptic potentials (e.p.s.ps) lasting 3-10 min were evoked by repetitive
      electrical stimulation of the mesenteric nerves. Prolonged depolarizations were
      also evoked in most tonic neurones by applications of substance P (SP),
      neurokinin A (NKA) or senktide, a tachykinin NK3 receptor agonist. 4. In most of
      phasic neurones (73%), mesenteric nerve stimulation did not induce an obvious
      depolarization but induced a prolonged inhibition of LAH lasting 3-10 min. Bath
      applied tachykinin receptor agonists similarly induced an inhibition of LAH
      without causing depolarization in most of the phasic neurones. 5. GR 71251 (5
      microM), a tachykinin NK1 receptor antagonist, partially depressed the nerve
      evoked slow e.p.s.ps in tonic neurones and the nerve-evoked LAH inhibition in
      phasic neurones. 6. Capsaicin (0.1-5 microM) induced a prolonged depolarization
      in tonic neurones and an inhibition of LAH in phasic neurones. 7. A mixture of
      peptidase inhibitors potentiated the depolarization and the LAH inhibition evoked
      by nerve stimulation, SP and NKA, but not those evoked by senktide. 8. It is
      concluded that tonic neurones respond to repetitive mesenteric nerve stimulation
      preferentially with slow e.p.s.ps and that phasic neurones respond preferentially
      with LAH inhibition. The present study further suggests that SP and NKA, released
      from axon collaterals of primary afferent neurones, produce slow e.p.s.ps in
      tonic neurones and the LAH inhibition in phasic neurones via NK1 receptors.

PMID- 8864544
TI  - Sources of calcium and alpha 1-adrenoceptor-mediated contraction in rat tail
      artery.
AB  - 1. The relative importance of intracellular and extracellular Ca2+ on alpha 1
      adrenoceptor-mediated contraction by noradrenaline and St-587 has been studied
      and correlated with the binding characteristics in intact tail artery from
      Sprague-Dawley rats. 2. Noradrenaline and St-587 behaved as full agonists
      inducing a concentration-dependent vasoconstriction. 3. Nifedipine (1 microM and
      10 microM) blocked by 50% (P < 0.001) and 75% (P < 0.001) respectively, the
      maximum contraction (Emax) induced by St-587. Nevertheless, to reach 40%
      inhibition of Emax on noradrenaline responses (P < 0.01), 10 microM nifedipine
      was necessary. 4. Both agonists induced a concentration-dependent accumulation of
      inositol phosphates. Noradrenaline behaved as a full agonist and St-587 as a
      partial agonist for this response. 5. [3H]-prazosin binding to intact tail artery
      rings was saturable and of high affinity (KD = 4.44 +/- 0.46 nM; Bmax = 36.35 +/-
      4.22 fmol mg-1 tissue). 6. Competition curves for inhibition of specific [3H]
      prazosin binding by WB-4101 suggest that the rat tail artery contains two alpha 1
      adrenoceptor subtypes in an approximate ratio of 60:40. 7. After irreversible
      alkylation of alpha 1B-adrenoceptors with 100 microM chloroethylclonidine (CEC),
      nifedipine (1 microM) influenced to a greater extent the St-587- than the
      noradrenaline-induced contraction. 8. Our results indicate that the degree of
      participation of intracellular and extracellular Ca2+ sources, on the alpha 1
      adrenoceptor-mediated contraction, depends on the agonist used. The two alpha 1
      adrenoceptor subtypes observed in binding experiments seem to be unrelated to the
      Ca2+ sources used for contraction.

PMID- 8864545
TI  - Differential effects of nitric oxide donors on basal and electrically evoked
      release of acetylcholine from guinea-pig myenteric neurones.
AB  - 1. The effects of the nitric oxide (NO) donors, 3-morpholino-sydnonimine (SIN-1),
      S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside on basal and
      electrically evoked release of [3H]-acetylcholine were studied in myenteric
      plexus longitudinal muscle preparations of the guinea-pig small intestine
      preincubated with [3H]-choline. 2. The NO donors concentration-dependently
      increased basal release of [3H]-acetylcholine. The increase in release was
      calcium-dependent and was prevented in the presence of tetrodotoxin. Superoxide
      dismutase (150 u ml-1) potentiated the effect of SIN-1. The selective inhibitor
      of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one
      (ODQ, 0.01-1 microM), antagonized the facilitatory effect of SNAP. 8-Bromo cyclic
      GMP and the cyclic GMP-specific phosphodiesterase inhibitor, zaprinast (both 0.1
      1 mM), also enhanced basal [3H]-acetylcholine release. The effect of 10 microM
      SNAP was significantly enhanced in the presence of zaprinast. 3. The NO donors
      concentration-dependently inhibited the electrically evoked release of [3H]
      acetylcholine, whereas 8-bromo cyclic GMP and zaprinast enhanced the evoked
      release. The inhibition of acetylcholine release by SNAP was not affected by ODQ
      (0.01-1 microM). 4. It is concluded that NO stimulates basal acetylcholine
      release from myenteric neurones through activation of guanylyl cyclase. In
      addition, NO inhibits the depolarization evoked release of acetylcholine by a
      presynaptic mechanism unrelated to cyclic GMP. The data imply that NO is not only
      an inhibitory transmitter to intestinal smooth muscles but also a modulator of
      cholinergic neurotransmission in the myenteric plexus.

PMID- 8864546
TI  - Intranasal administration of neuropeptide Y in man: systemic absorption and
      functional effects.
AB  - 1. Exogenous neuropeptide Y (NPY, 10 nmol, 50 nmol and 100 nmol) and its vehicle
      (NaCl 0.9%) were administered in a double blind, randomized and controlled manner
      by intranasal spray in 7 healthy volunteers. Variations of plasma NPY
      concentration over time were measured during 120 min. Forty min after the
      administration of 50 nmol and 100 nmol of exogenous NPY, plasma NPY increased
      from 5.5 +/- 1.1 pM to 9.8 +/- 2.3 pM (P < 0.05) and from 9.06 +/- 5.1 pM to 20.8
      +/- 6.16 pM (P < 0.001), respectively. There was no significant modification of
      the mean arterial blood pressure and no subjective discomfort was reported. 2.
      Nasal airway resistance (NAR) was measured by anterior rhinomanometry and was
      reduced by 25 +/- 3% and 32 +/- 5% after the spray of 50 nmol and 100 nmol,
      respectively, for about 90 min. 3. Double-blind, randomized, placebo-controlled
      and 3-way crossover design experiments were performed in 8 healthy volunteers to
      evaluate the influence of intranasal pretreatment with NPY (20 nmol) and the
      mixed alpha 1/alpha 2-adrenoceptor agonist oxymetazoline (20 nmol) on the
      functional effects of subsequent local irritation evoked by capsaicin (3.3 x 10(
      4) mol). Subjective evaluation of NAR and local intensity of discomfort were
      evaluated by means of a visual analogue scale. Nasal secretions were collected
      and objective NAR was recorded by rhinomanometry. 4. Subjective NAR, nasal
      secretions and rhinomanometry recordings were not modified by intranasal
      application of saline, NPY or oxymetazoline. Subjective nasal obstruction, local
      discomfort, nasal secretions and NAR increase evoked by capsaicin were markedly
      reduced by NPY pretreatment (P < 0.05) when compared to saline or oxymetazoline.
      5. It is concluded that intranasal application of exogenous NPY has very low
      systemic absorption but induced long lasting nasal vasoconstriction without
      cardiovascular effects. Pretreatment of the nasal mucosa with exogenous NPY
      reduces both secretagogue and vasodilator responses to subsequent application of
      capsaicin.

PMID- 8864547
TI  - Differences between the third cardiac beta-adrenoceptor and the colonic beta 3
      adrenoceptor in the rat.
AB  - 1. The heart of several species including man contains atypical beta
      adrenoceptors, in addition to coexisting beta 1- and beta 2-adrenoceptors. We now
      asked the question whether or not the third cardiac beta-adrenoceptor is
      identical to the putative beta 3-adrenoceptor. We compared the properties of the
      third cardiac beta-adrenoceptor with those of beta 3-adrenoceptors in isolated
      tissues of the rat. To study the third cardiac beta-adrenoceptor we used
      spontaneously beating right atria, paced left atria and paced left ventricular
      papillary muscles. As a likely model for putative beta 3-adrenoceptors we studied
      atypical beta-adrenoceptors of the colonic longitudinal muscle precontracted with
      30 mM KCl. We used beta 3-adrenoceptor-selective agonists, antagonists and non
      conventional partial agonists (ie high-affinity blockers of both beta 1- and beta
      2-adrenoceptors know to exert also stimulant effects through beta 3
      adrenoceptors). 2. The non-conventional partial agonist (-)-CGP 12177 caused
      positive chronotropic effects in right atria (pD2 = 7.3) and positive inotropic
      effects in left atria (pD2 = 7.5). The stimulant effects of (-)-CGP 12177 were
      resistant to blockade by 200 nM-2 microM (-)-propranolol and 3 microM ICI 118551
      (a beta 2-selective antagonist) but antagonized by 1 microM (-)-bupranolol (pKB =
      6.4-6.8), 3 microM CGP 20712A (a beta 1-selective antagonist) (pKB = 6.3-6.4) and
      6.6 microM SR 59230A (a beta 3-selective antagonist, pKB = 5.1-5.4). 3. The non
      conventional partial agonist cyanopindolol caused positive chronotropic effects
      in right atria (pD2 = 7.7) and positive inotropic effects in left atria (pD2 =
      7.1). The stimulant effects of cyanopindolol were resistant to blockade by 200 nM
      (-)-propranolol but antagonized by 1 microM (-)-bupranolol (pKB = 6.8-7.1). 4.
      Neither (-)-CGP 12177 nor cyanopindolol caused stimulant effects in papillary
      muscles at concentrations between 0.2 nM and 20 microM. 5. In the presence of 200
      nM (-)-propranolol the beta 3-adrenoceptor-selective agonists BRL 37344 (6
      microM), SR 58611A (6 microM), ZD 2079 (60 microM) and CL 316243 (60 microM) did
      not cause stimulant effects or modify the potency and efficacy of the effects of
      (-)-CGP 12177 in right and left atria. The combination of 2 microM (-)
      propranolol and 2 microM (-)-noradrenaline did not modify the chronotropic
      potency and efficacy of (-)-CGP 12177 compared to the potency and efficacy in the
      presence of 2 microM (-)-propranolol alone. 6. (-)-CGP 12177 relaxed the colon
      with a pD2 of 6.9 and a maximum effect of 55% compared to (-)-isoprenaline. The
      relaxant effects of (-)-CGP 12177 were resistant to blockade by 200 nM (-)
      propranolol, 3 microM CGP 20712A, 3 microM ICI 118551 but blocked by 2 microM (-)
      propranolol (pKB = 6.0), 1 microM (-)-bupranolol (pKB = 6.4) and 3 microM SR
      59230A (pKB = 6.3). In the presence of 200 nM (-)-propranolol, (-)-CGP 12177 (20
      microM) antagonized surmountably the relaxant effects of BRL 37344 (pKP = 7.3) (
      )-noradrenaline (pKP = 7.0); and CL 316243 (pKP = 7.0). 7. Cyanopindolol in the
      presence of 200 nM (-)-propranolol relaxed the colon with a pD2 of 7.0 and a
      maximum effect of 40% compared to (-)-isoprenaline. As expected from a partial
      agonist, cyanopindolol antagonized the relaxant effects of both BRL 37344 and CL
      316243 with a pKP = 7.6 and (-)-noradrenaline with a pKP = 7.4. 8. The following
      beta 3-adrenoceptor-selective agonists were potent colonic relaxants (pD2 values
      between parentheses): BRL 37344 (9.1), ZD 2079 (7.0), CL 316243 (9.0) and SR
      58611A (8.2). The relaxant effects of these agonists were only marginally
      affected by 200 nM (-)-propranolol, not blocked by 3 microM CGP 20712A or 3
      microM ICI 118551, and blocked by SR 59230A 3 microM (pKB = 6.9-7.5), 1 microM (
      )-bupranolol (pKB = 6.2-6.4) and 2 microM (-)-propranolol (pKB = 6.3-6.5). 9...

PMID- 8864548
TI  - Effects of agents which elevate cyclic AMP on guinea-pig eosinophil homotypic
      aggregation.
AB  - 1. Eosinophil recruitment and activation in inflamed tissue is thought to play an
      important role in the pathophysiology of allergic diseases. Experimental evidence
      suggests that elevating cyclic AMP is an effective means of reducing eosinophil
      recruitment in vivo and may therefore have therapeutic benefit. In the present
      study, we have assessed the capacity of cyclic AMP-elevating agents to modulate
      guinea-pig eosinophil homotypic aggregation, a CD18-dependent process, which may
      be an important component of eosinophil function in vivo. 2. Prostaglandin E1
      (PGE1, 10(-16) to 10(-6) M) inhibited platelet activating-factor (PAF)- and C5a
      induced eosinophil aggregation in a concentration-dependent manner. However, PAF
      induced responses were more potently and more effectively inhibited by PGE1. The
      inhibitory effects of PGE1 on PAF-induced aggregation were reversed by
      pretreatment of eosinophils with the protein kinase A inhibitors H89 and KT5720.
      3. The beta 2-adrenoceptor agonists, salbutamol and salmeterol, concentration
      dependently inhibited eosinophil aggregation induced by C5a and PAF and, again.
      PAF-induced responses were more effectively reduced. The inhibitory effect of
      salmeterol was mediated by beta-adrenoceptors, as assessed by the reversal after
      pretreatment with propranolol. 4. Rolipram, a selective phosphodiesterase 4
      (PDE4) inhibitor, also attenuated PAF- and C5a-induced aggregation and at a low
      concentration which did not affect aggregation per se, had a synergistic effect
      with PGE1 and salbutamol to suppress this response. 5. Activation of eosinophils
      with PAF or C5a induced a small but significant increase in the level of CD18
      expression on the eosinophil surface. PGE1 (10(-7) M) decreased PAF- and C5a
      induced upregulation of CD18 by 93% and 62%, respectively. 6. These results
      demonstrate that cyclic AMP-elevating agents effectively inhibit eosinophil
      aggregation, a CD18-dependent functional response. Because CD18 has been shown to
      be important for eosinophil recruitment to inflamed tissue in vivo, our findings
      may be of relevance to the efficacy of cyclic AMP-elevating agents at inhibiting
      eosinophil trafficking.

PMID- 8864549
TI  - Characterization of tachykinin receptors mediating plasma extravasation and
      vasodilatation in normal and acutely inflamed knee joints of the rat.
AB  - 1. Inflammatory actions of tachykinins in normal rat knee joints were compared
      with those of animals with acutely inflamed joints induced by intra-articular
      injection of 2% carrageenan. Plasma protein extravasation in rat knee joints,
      measured by protein micro-turbidimetry, was induced by intra-articular perfusion
      of selective tachykinin receptor agonists. Changes in joint blood flow, measured
      by laser Doppler perfusion imaging, were produced by topical applications of
      selective tachykinin receptor agonists to the joint capsule. 2. Carrageenan
      injected rat knee joints showed significantly higher (P < 0.001) basal plasma
      extravasation (56 +/- 4 micrograms ml-1, n = 5) than normal rat knee joints (10
      +/- 4 micrograms ml-1, n = 6). Intra-articular perfusion of the selective
      neurokinin1 (NK1) receptor agonist [Sar9, Met(O2)11]-substance P (0.8 nmol min-1)
      for 60 min elevated the basal plasma extravasation to 90 +/- 17 micrograms ml-1
      (n = 6, P < 0.001) in normal joints, and to 150 +/- 14 micrograms ml-1 (n = 5, P
      < 0.001) in inflamed joints. Perfusion of the selective NK1 receptor antagonist
      N2-[(4R)-4-hydroxy-1-(1-methyl-1H- indol-3-yl)carbonyl-L-prolyl]-N-methyl-N
      phenylmethyl-3-(2-naphthyl)- L-alaninamide (FK888; 0.8 nmol min-1) for 20 min
      followed by co-perfusion with the NK1 receptor agonist (0.8 nmol min-1) produced
      complete inhibition of the NK1 receptor agonist-induced plasma extravasation in
      the two groups of animals (for both groups; n = 3, P < 0.001). 3. Intra-articular
      perfusion of the selective NK receptor agonist [Nle10]-neurokinin A4-10 (0.8 nmol
      min-1) and the selective NK3 receptor agonist [MePhe7]-neurokinin B (0.8 nmol
      min1) produced no increase in plasma extravasation in normal or in inflamed rat
      knee joints (n = 4 and 11, P > 0.05). 4. Topical bolus applications of the NK1
      receptor agonist [Sar9, Met(O2)11]-substance P onto normal joint capsules
      produced dose-dependent vasodilatation expressed as a voltage increase from
      control level. The maximum increase in blood flow was 2.05-0.21 V from a basal
      voltage of 3.42 +/- 0.07 V (n = 13, P < 0.001). To a much lesser extent,
      administration of the NK2 receptor agonist [Nle10]-neurokinin A4-10 also produced
      dose-dependent vasodilatation with maximum increase of 0.46 +/- 0.08 V from a
      basal level of 3.38 +/- 0.1 V (n = 7, P < 0.01). Animals with acutely inflamed
      joints showed enhanced vasodilator responses to the NK1 and NK2 receptor agonists
      (for both: P vs non-inflamed joints < 0.001). Thus, the NK1 and NK2 receptor
      agonists produced maximum increases of 2.56 +/- 0.19 V (basal level = 5.84 +/-
      0.07 V; n = 7, P < 0.001) and 1.97 +/- 0.26 V (basal level = 6.31 +/- 0.23 V; n =
      11, P < 0.001), respectively. The NK3 receptor agonist [MePhe7]-neurokinin B
      produced no change in blood flow in normal or in inflamed rat knee joints (n = 7
      and 5, P > 0.05). 5. Bolus administration of the NK1 receptor antagonist FK888
      (10 pmol) alone followed 5 min later by another dose of 10 pmol FK888 (i.e. total
      dose of 2 x 10 pmol) applied together with the NK1 receptor selective agonist
      [Sar9, Met(O2)11]-substance P produced partial, but significant inhibition of the
      NK1 receptor agonist-induced vasodilatation in both normal (maximum response
      reduced by 51.9 +/- 5.4%; n = 6, P < 0.001) and inflamed rat knee joints (maximum
      response reduced by 49.3 +/- 6.1%; n = 5, P < 0.001). The NK2 receptor agonist
      [Nle10]-neurokinin A4-10-induced vasodilator responses in inflamed joints were
      not affected by this treatment (n = 6, P > 0.05). However, with two higher doses
      of FK888 (both 1 nmol), the NK1 and the NK2 receptor agonist-induced vasodilator
      responses were abolished in the two groups of animals (n = 6-8, P < 0.005). 6.
      Administration of two doses of the selective NK2 receptor antagonist (S)-N-methyl
      N-[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl) -butyl]benzamide
      (SR48968;...

PMID- 8864550
TI  - Potentiation of chloride responses to glycine by three 5-HT3 antagonists in rat
      spinal neurones.
AB  - 1. Modulations of Cl- responses to glycine by 5-hydroxytryptamine ligands were
      studied in cultured spinal neurones, by the whole-cell recording technique. 2.
      Three 5-HT3 antagonists were found to potentiate reversibly responses to low
      concentrations of glycine. Potentiations were induced by micromolar
      concentrations of LY-278,584 (1-10 microM) and by concentrations of MDL-72222 or
      ICS-205,930 between 10 nM and 1 microM. 3. Potentiations were observed over the
      whole voltage range without any change in the reversal potential of the glycine
      responses and without affecting the resting conductance. 4. The degree of
      potentiation was variable among cells. It increased with the concentration of the
      modulator, but only up to 100 nM for MDL-72222 and ICS-205,930. 5. The
      potentiation appeared to result from an increase in the affinity for glycine of
      glycine receptors. 6. Neither the blockade of glycine uptake by Na+ removal, nor
      the excision of membrane patches prevented the potentiation. 7. At high
      concentrations (10 microM), both MDL-72222 and ICS-205,930 had, in contrast, a
      blocking effect on glycine responses. 8. Potentiation by LY-278,584 and a dose
      dependent modulation by MDL-72222 were also observed for taurine responses. 9.
      The effects on glycine responses of various ligands of 5-HT3 receptors (including
      agonists) are discussed. The ability of LY-278,584, MDL-72222 and ICS-205,930 to
      potentiate glycine responses appears to be independent of their known 5-HT3
      receptor antagonist properties. It would be interesting to look for chemically
      related drugs that would be specific potentiators of glycine responses.

PMID- 8864551
TI  - Characterization of [125I]-endothelin-1 and [125I]-BQ3020 binding to rat
      cerebellar endothelin receptors.
AB  - 1. We performed radioligand binding experiments on rat cerebellar homogenates
      using [125I]-endothelin-1 ?[1251]-ET-1? and [125I]-BQ3020 to examine the
      pharmacology of endothelin receptors in rat brain. Saturation experiments
      demonstrated a single population of binding sites with high affinity for both
      radioligands ([125I]-ET-1, pKd = 8.94 +/- 0.17; [125I]-BQ3020, pKd = 9.18 +/-
      0.14 nM; mean +/- s.e.mean). However, [125I]-BQ3020 only recognised approximately
      one third the number of endothelin receptors measured with [125I]-ET-1. 2.
      Saturation binding experiments with [125I]-PD151242 revealed high affinity
      binding to a single population of ETA receptors in the cerebellar homogenates
      (pKd = 9.95 +/- 0.14; Bmax = 30 +/- 15 fmol mg-1 protein). 3. Competition
      experiments were performed with ligands that are either non-selective for
      endothelin receptor subtypes. The rat cerebellar endothelin receptor displayed a
      high affinity for endothelin-1 (ET-1), endothelin-3 (ET-3) and sarafotoxin-S6c
      (STX-6c) although the affinity for ET-3 was slightly higher than the affinity for
      ET-1 using both radioligands. The selective ETA antagonists, BQ123, BMS-182,874
      and JKC-301 all displayed low affinities at the endothelin receptors. In contrast
      the selective ETB agonists, IRL1620 and [Ala1,3,11,15]ET-1 and the selective ETB
      antagonist, BQ-788 had moderate affinities at the endothelin receptor, in the low
      nanomolar range. The ETB agonist, BQ3020, had approximately 10 fold higher
      affinity than IRL1620 and [Ala1,3,11,15]ET-1 at the rat cerebellar endothelin
      receptors. The non-selective antagonists, Ro-46,2005, Ro-47,0203 and PD-142,893
      displayed moderate affinities at the cerebellar receptor. 4. Since [125I]-BQ3020
      recognises only a fraction of the [125I]-ET-1 binding sites, the majority of the
      endothelin receptors in the cerebellum cannot be classed as ETB. Although [125I]
      PD151242 was able to detect ETA receptors in the rat cerebellar homogenates, the
      small population of ETA receptors (2% of the total endothelin population as
      measured with [125I]-ET-1) could not account for the non-ETB receptor population.
      We conclude that the rat brain cerebellar receptor has a profile similar to the
      ETB1 receptor as it has a high affinity for ET-1, ET-3, STX-6c and was moderately
      sensitive to PD-142,893. However, as the ETB ligands BQ-788, IRL1620 and
      [Ala1,3,11,15]ET-1 have only a moderate affinity for the rat cerebellar
      endothelin receptor and since ET-3 has a higher affinity as compared to ET-1, our
      findings suggest that the rat cerebellum contains predominately ETc receptors.

PMID- 8864552
TI  - The effect of isoenzyme-selective PDE inhibitors on methacholine-induced
      contraction of guinea-pig and rat ileum.
AB  - 1. We have examined the effects of the isoenzyme-selective phosphodiesterase
      (PDE) inhibitors, vinpocetine (type 1), siguazodan (type 3), rolipram (type 4)
      and zaprinast (type 5) and the non-selective PDE inhibitor enprofylline on
      methacholine (MCh) contractile concentration-response curves on guinea-pig and
      rat isolated ileum. 2. In guinea-pig ileum, vinpocetine (10-300 microM),
      zaprinast (1-300 microM) and enprofylline (100-1000 microM) produced a
      concentration-dependent depression of the maximum response (Emax) to MCh only
      without effect on the MCh EC50 values (rank order of potency: zaprinast >
      vinpocetine > enprofylline). In contrast, siguazodan (10-300 microM) and rolipram
      (10-300 microM) produced a rightward displacement of the MCh concentration
      response curve (increase in EC50: rank order; rolipram > siguazodan), with
      effects on the MCh maximum seen only at higher concentrations. 3. In the rat
      ileum, vinpocetine (10-300 microM), zaprinast (0.1-300 microM) and enprofylline
      (100-1000 microM) caused depression of the MCh maximum contraction (rank order:
      zaprinast > vinpocetine > enprofylline). Low concentrations of rolipram and
      siguazodan had no significant effect on the MCh maximum. In the presence of
      higher concentrations (> 100 microM) of rolipram and siguazodan, a maximum
      response was not achieved at the highest concentration of MCh tested. As in the
      guinea-pig ileum, only rolipram (10-300 microM) and siguazodan (10-300 microM)
      produced a significant, concentration-dependent, rightward displacement of the
      MCh concentration-response curve (increase in EC50: rank order: rolipram >
      siguazodan). 4. In the guinea-pig ileum, isoprenaline (0.1 microM) produced a
      rightward displacement (approximately 3 fold) of the MCh concentration-response
      curve, accompanied by a significant depression of the maximum response.
      Increasing the isoprenaline concentration (1 microM) had no further effect on
      either parameter. Sodium nitroprusside (SNP, > or = 10 microM) produced a
      concentration-dependent depression of the MCh maximum without an effect on the
      EC50. 5. In the rat ileum, isoprenaline (1 microM) produced a concentration
      dependent rightward displacement (approximately 2.8 fold) of the MCh
      concentration-response curve with depression of the MCh maximum at higher (> or =
      100 microM) concentrations. SNP produced depression of the MCh maximum at a
      concentration of 10 microM and above. Effects on the MCh EC50 were seen only at
      100 and 300 microM. 6. In guinea-pig ileum, isoprenaline (0.1 microM) in
      combination with rolipram (10 microM) further increased the MCh EC50 and reduced
      the MCh maximum. The combination of SNP (10 microM) with zaprinast (0.1 microM)
      produced no further significant effect than SNP alone. 7. In rat ileum,
      isoprenaline (1 microM) in combination with rolipram (10 microM) further
      increased the EC50 and reduced the maximum. SNP (10 microM) had no significant
      effect on either the MCh maximum or EC50. A combination with zaprinast (1 microM)
      had no further effect. 8. In conclusion, all the PDE inhibitors tested produced a
      concentration-dependent inhibition of the MCh concentration-response curve,
      indicating a modulator role for the PDE isoenzymes in gastrointestinal smooth
      muscle contractility. The PDE inhibitors that elevate cyclic GMP produced a
      depression of the MCh maximum response only, whilst those that elevate cyclic AMP
      produced a rightward displacement of the MCh concentration-response curve. This
      was confirmed by the use of isoprenaline and SNP. This difference in the type of
      inhibition produced by these PDE isoenzyme inhibitors may reflect a different
      intracellular site/mechanism by which the cyclic AMP- and cyclic GMP-activated
      kinases act functionally to antagonize the contractile response.

PMID- 8864553
TI  - Synergistic inhibition of thrombin-induced platelet aggregation by the novel
      nitric oxide-donor GEA 3175 and adenosine.
AB  - 1. The influence of the novel nitric oxide-donor GEA 3175 on thrombin- and
      ionomycin-stimulated human platelets was investigated. The effect of GEA 3175 was
      compared with that of adenosine, an activator of platelet adenylyl cyclase. 2.
      GEA 3175 inhibited thrombin-induced secretion of ATP but did not affect
      aggregation; similar results were obtained with adenosine. 3. Thrombin-stimulated
      rises in the cytosolic free Ca2+ concentration, [Ca2+]i, were dose-dependently
      inhibited by GEA 3175 and adenosine. GEA 3175 and adenosine maximally reduced the
      initial rise in [Ca2+]i by 41% and 35%, respectively. 4. Simultaneous exposure to
      GEA 3175 and adenosine nearly abolished both the functional responses (i.e.
      aggregation and degranulation) and the rises in [Ca2+]i in thrombin-stimulated
      platelets. 5. Aggregation and increases in [Ca2+]i triggered in platelets by the
      Ca(2+)-ionophore ionomycin were only marginally affected by a combination of GEA
      3175 and adenosine. 6. GEA 3175 potently increased the guanosine 3':5'-cyclic
      monophosphate (cyclic GMP) content in platelets but did not affect adenosine
      3':5'-cyclic monophosphate (cyclic AMP) levels. Adenosine did not increase either
      the cyclic AMP or the cyclic GMP levels in platelets. However, adenosine and GEA
      3175 combined significantly elevated the platelet cyclic AMP content. 7. The
      results show that simultaneous exposure to GEA 3175 and adenosine promotes potent
      anti-aggregatory properties in platelets in vitro. The findings suggest that
      blockage of the cytosolic Ca(2+)-signal, which is probably mediated by an
      amplified cyclic nucleotide response, is an important event during the
      synergistic inhibition of thrombin-induced aggregation.

PMID- 8864554
TI  - Effects of caffeine and 3-isobutyl-1-methylxanthine on voltage-activated
      potassium currents in vertebrate neurones and secretory cells.
AB  - 1. The effects of caffeine and 3-isobutyl-l-methylxanthine (IBMX) on voltage
      activated K+ currents were examined by use of patch clamp recording techniques in
      dissociated chick autonomic ganglion neurones, chick pineal cells and rat
      anterior pituitary cells. 2. In chick ciliary ganglion neurones, caffeine (0.1-10
      mM) produced a robust blockade of delayed rectifier K+ currents (IDR). Blockade
      was rapid in onset and concentration- and voltage-dependent. Caffeine produced
      greater inhibition with larger depolarizing voltage pulses. Similar inhibition of
      IDR was observed in excised outside-out 'maxi-patches' indicating a direct effect
      on the K+ channels. Caffeine also inhibited IDR in chick sympathetic neurones,
      chick pineal cells and rat anterior pituitary cells. 3. Application of 10 mM
      caffeine caused inhibition of transient A-currents (IA) in chick ciliary ganglion
      neurones. Inhibition of IA was voltage-dependent with greater inhibition observed
      at more positive command potentials. Application of 1 mM caffeine did not cause
      inhibition of IA. 4. Application of 1 mM IBMX, a structural analogue of caffeine,
      caused inhibition of IDR and IA in chick ciliary ganglion neurones. The voltage
      dependence of the inhibition of both currents was qualitatively different from
      that observed with caffeine. The inhibitory effects of 1 mM IBMX and 10 mM
      caffeine on IDR and IA were additive. 5. Direct inhibition of voltage-activated
      K+ currents can potentially produce significant secondary effects on
      intracellular free Ca2+. These results indicate that caution must be used in the
      design and interpretation of experiments in which millimolar concentrations of
      caffeine or IBMX are used in pharmacological studies of intracellular Ca2+
      dynamics or other second messenger mechanisms.

PMID- 8864555
TI  - Facilitation of imipramine efflux from the brain by systemic specific antibodies.
AB  - 1. This study investigated the capacity of circulating anti-tricyclic
      antidepressant (TCA) IgG to increase the efflux of imipramine (Imip) from the rat
      brain. 2. A tracer amount of [3H]-Imip (40 pmol) was injected into the cerebral
      lateral ventricle and its efflux was determined in control rats and in rats given
      anti-TCA antibody. The monoclonal anti-TCA IgG1 was injected i.v. 48 h before
      Imip at 4 IgG:Imip molar ratios (10, 100, 1000 and 10,000). The [3H]-Imip in
      arterial and venous plasma was measured for up to 60 min, and in the brain and
      peripheral organs (heart, liver, lung, kidney) 5 and 60 min after Imip injection.
      3. The arterial plasma concentration of Imip in control rats was significantly
      higher (26.7 +/- 2.1 pM) than the venous one (17.7 +/- 2.0 pM) at 5 min,
      indicating that Imip released from brain becomes distributed in peripheral
      tissues. These concentrations were not significantly different at 60 min
      suggesting that Imip was, at this time, redistributing from extravascular tissues
      to the blood. In rats given anti-TCA IgG, any Imip leaving the brain was
      immediately bound by the circulating antibody at 5 min. This greatly reduced the
      Imip in the heart (63.9%) and lung (61.3%) at the highest IgG:Imip ratio. The
      brain Imip was markedly lower at 60 min (31.5% with an IgG Imip ratio of 1000 and
      57.5% at a ratio of 10,000). The two lowest IgG:Imip ratios had less effect on
      the plasma Imip because of the relative low affinity of the anti-TCA IgG (3.8 x
      10(7) M-1). 4. These data indicate that the anti-TCA IgG facilitated the efflux
      of Imip from the brain, even though these antibodies cannot cross the blood-brain
      barrier. This may be an efficient system for increasing drug organ clearance, as
      more than half the Imip in the brain was actively removed by the antibody in 1 h.

PMID- 8864556
TI  - Delayed protection against ischaemia-induced ventricular arrhythmias and infarct
      size limitation by the prior administration of Escherichia coli endotoxin.
AB  - 1. Bacterial endotoxin (lipopolysaccharide derived from Escherichia coli) was
      injected intraperitoneally in conscious rats in doses ranging from 0.5 to 2.5 mg
      kg-1. At various times afterwards the animals were anaesthetized and subjected to
      a 30 min period of left coronary artery occlusion. 2. Under these conditions the
      severity of ventricular arrhythmias was markedly suppressed, in comparison with
      saline-injected controls, but this was particularly marked with the higher doses
      (1.5 and 2.5 mg kg-1); the number of ventricular premature beats was reduced from
      1687 +/- 227 over the 0.5 h coronary artery occlusion period to 190 +/- 46 in
      those rats administered 2.5 mg kg-1 endotoxin 8 h previously (P < 0.05). The
      duration of ventricular tachycardia was also significantly reduced (138 +/- 26 s
      to 8.9 +/- 4.2 s; P < 0.01) and there was a reduction in the incidence of
      ventricular fibrillation (from 56% to 10%). 3. The time course of this protection
      was studied following the administration of a single dose of 2.5 mg kg-1 of
      endotoxin by anaesthetizing rats 4, 8 or 24 h later. Protection was apparent at
      each time but was particularly marked at 8 h. 4. No rat given the highest dose of
      endotoxin (32 in all) died as a result of ventricular fibrillation, or from any
      other cause, during an occlusion, in contrast to a 26% mortality in the controls
      (P < 0.01). 5. Infarct size, measured following a 30 min period of coronary
      artery occlusion followed by a 3 h reperfusion period, was reduced both 8 and 24
      h after the administration of 2.5 mg kg-1 endotoxin (reductions of 24.3 and 23.1%
      respectively; P < 0.05). Endotoxin had no significant effect on the area at risk.
      6. The beneficial effects of endotoxin on infarct size and on ventricular
      arrhythmias were markedly attenuated by the prior administration of
      dexamethasone, 3 mg kg-1 given 1 h prior to endotoxin administration.
      Dexamethasone itself reduced infarct size (P < 0.05) but had no direct effect on
      arrhythmia severity following coronary artery occlusion. 7. The mechanisms of
      this "cross-tolerance' induced by bacterial endotoxin against ischaemia
      reperfusion injury remain to be elucidated but the most likely mechanisms appear
      to be the induction of protective enzymes or proteins (e.g. nitric oxide
      synthase, cyclo-oxygenase (COX) 2) probably mediated by cytokine release.

PMID- 8864557
TI  - Rapid nitric oxide- and prostaglandin-dependent release of calcitonin gene
      related peptide (CGRP) triggered by endotoxin in rat mesenteric arterial bed.
AB  - 1. Our objective was to determine whether endotoxin (ETX) could directly trigger
      the release of calcitonin gene-related peptide (CGRP) from perivascular sensory
      nerves in the isolated mesenteric arterial bed (MAB) of the rat and to determine
      whether nitric oxide (NO) and prostaglandins (PGs) are involved. 2. ETX caused
      time- and concentration-dependent release of CGRP, and as much as a 17 fold
      increase in CGRP levels in the perfusate at 10-15 min after the administration of
      ETX (50 micrograms ml-1). 3. CGRP-like immunoreactivity in the perfusate was
      shown to co-elute with synthetic rat CGRP by reverse-phase h.p.l.c. 4.
      Pretreatment of MAB with capsaicin or ruthenium red inhibited ETX-induced CGRP
      release by 90% and 71%, respectively. ETX-evoked CGRP release was decreased by
      84% during Ca2(+)-free perfusion. 5. The release of CGRP evoked by ETX was
      enhanced by L-arginine by 43% and inhibited by N omega-nitro-L-arginine (L-NOARG)
      and methylene blue by 37% and 38%, respectively. L-Arginine reversed the effect
      of L-NOARG. 6. Indomethacin and ibuprofen also inhibited the ETX-induced CGRP
      release by 34% and 44%, respectively. No additive inhibition could be found when
      L-NOARG and indomethacin were concomitantly incubated. 7. The data suggest that
      ETX triggers the release of CGRP from capsaicin-sensitive sensory nerves
      innervating blood vessels. The ETX-induced CGRP release is dependent on
      extracellular Ca2+ influx and involves a ruthenium red-sensitive mechanism. Both
      NO and PGs appear to be involved in the ETX-induced release of CGRP in the rat
      mesenteric arterial bed.

PMID- 8864558
TI  - Influence of superoxide dismutase inhibition on the discrimination between NO and
      the nitrergic neurotransmitter in the rat gastric fundus.
AB  - 1. The influence of diethyldithiocarbamate (DETCA), that irreversibly inhibits
      Cu/Zn-containing superoxide dismutase, on the inability of 6-anilino-5,8
      quinolinedione (LY83583), hypoxanthine/xanthine oxidase, hydroquinone and
      hydroxocobalamin to reduce electrically-induced NANC relaxations in the rat
      gastric fundus was investigated. 2. Longitudinal muscle strips of the rat gastric
      fundus were mounted for auxotonic recording in the presence of atropine and
      guanethidine and tone was raised by administration of prostaglandin F2 alpha
      DETCA (3 x 10(-3) M) slightly reduced the short-lasting relaxations induced by
      10(-5) M exogenous nitric oxide (NO) and transmural electrical stimulation for 10
      s at 4 Hz but this effect was not influenced by 1000 u ml-1 superoxide dismutase
      (SOD). 3. DETCA (3 x 10(-5) -3 x 10(-3) M) concentration-dependently potentiated
      the inhibitory effect of LY83583 upon the electrically-induced relaxations,
      although this was less pronounced than the inhibition of the NO-induced
      relaxations. The inhibition of the electrically-induced non-adrenergic non
      cholinergic (NANC) relaxations was not reversed by SOD while that of the NO
      induced relaxations was partially reversed. 4. The inhibitory effect of
      hypoxanthine/xanthine oxidase, hydroquinone and hydroxocobalamin on the
      electrically-induced NANC relaxations in the presence of DETCA (3 x 10(-3) M) was
      not different from the inhibitory effect of DETCA alone. 5. It was concluded that
      the differentiating effect of LY83583 between exogenous NO and the endogenous
      nitrergic neurotransmitter is partially related to protection of the endogenous
      nitrergic neurotransmitter by high levels of intracellular superoxide dismutase.
      This mechanism does not hold for hydroquinone and hydroxocobalamin, as they still
      discriminate between exogenous NO and the endogenous nitrergic neurotransmitter
      in the presence of DETCA. The possibility that the endogenous nitrergic
      neurotransmitter is not free NO in the rat gastric fundus therefore remains open.

PMID- 8864559
TI  - Inhibition by antioxidants of nitric oxide synthase expression in murine
      macrophages: role of nuclear factor kappa B and interferon regulatory factor 1.
AB  - 1. In view of the potential deleterious effects of high amounts of nitric oxide
      (NO) produced by the inducible isoform of NO synthase (iNOS) in inflammation, the
      prevention of the expression of this enzyme represents an important therapeutic
      goal. In cytokine-stimulated cells, activation of nuclear factor kappa B (NF
      kappa B) is crucial for the increase in iNOS gene expression. Since NF-kappa B
      activation appears to involve a redox-sensitive step, we have investigated
      whether three structurally unrelated antioxidants, 5,7-dihydroxyflavone
      (chrysin), 3,4-dichloroisocoumarin (DCI) and N-acetyl 5-hydroxytryptamine (N
      acetylserotonin, NAS), affect iNOS expression in cultured RAW 264.7
      monocyte/macrophages stimulated with bacterial lipopolysaccharide (LPS, 140 ng ml
      1) and interferon-gamma (IFN gamma, 5 u ml-1). 2. During a 6 h incubation period
      neither LPS nor IFN gamma alone exerted a significant effect but when combined,
      caused a prominent increase in nitrite formation, iNOS mRNA and protein
      abundance. Co-incubation with chrysin (50 microM), DCI (50 microM) or NAS (1 mM)
      markedly attenuated this increase in iNOS gene expression. 3. DCI, but not
      chrysin or NAS, prevented the activation of NF-kappa B in cells exposed to LPS
      plus IFN gamma for 30 min. In contrast, all three antioxidants significantly
      blunted the DNA-binding activity of interferon regulatory factor 1 (IRF-1), which
      mediates the synergistic effect of IFN gamma on iNOS gene expression in cells
      treated for 2 h with LPS plus IFN gamma. 4. DCI thus appears to inhibit iNOS gene
      expression at the transcriptional level by preventing the activation of both NF
      kappa B and IRF-1. The inhibitory effect of DCI on NF-kappa B activation,
      however, does not seem to be related to its antioxidative properties, since DCI,
      unlike chrysin or NAS, is a potent serine protease inhibitor which stabilizes the
      inactive NF-kappa B complex by protecting the inhibitory I kappa B-alpha subunit
      from proteolytic degradation. 5. The virtually identical inhibitory effect of
      chrysin, DCI and NAS on the activation of IRF-1 points to a redox-sensitive step
      in the activation of this transcription factor, which in contrast to NF-kappa B
      requires de novo protein synthesis. 6. Since iNOS gene expression in human cells
      and tissues usually requires the combination of several cytokines, antioxidants
      such as chrysin and NAS which do not interfere with the activation of NF-kappa B
      may be of therapeutic value for selectively inhibiting the enhanced expression of
      this enzyme in inflammation.

PMID- 8864560
TI  - Role of sarcoplasmic reticulum in inhibitory junction potentials and
      hyperpolarizations by nitric oxide donors in opossum oesophagus.
AB  - 1. Previous patch clamp studies of oesophageal circular muscle cells showed that
      nitric oxide (NO) modulated the opening of Ca2(+)-activated K+ channels involved
      in mediating the inhibitory junction potentials (i.j.ps). This study clarified
      the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in the
      mechanism of i.j.ps or hyperpolarizing responses to NO-releasing compounds.
      Electrical and mechanical activities were simultaneously recorded by
      intracellular microelectrode or double sucrose gap techniques. 2. The NO-donors,
      sydnonimine (SIN-1) and sodium nitroprusside, each at 500 microM, hyperpolarized
      oesophageal circular muscle cells by 15-20 mV, like i.j.ps. 3. The selective
      inhibitors of SR Ca2(+)-ATPase (cyclopiazonic acid 10-30 microM and thapsigargin
      5 microM) and the SR Ca2+ release channel activator (ryanodine 30 microM) caused
      depolarization and spontaneous contractions which were diminished after prolonged
      (> 30 min) incubation with these agents in Ca2(+)-containing medium. Moreover,
      these agents inhibited both the i.j.p. and NO-donor hyperpolarizations,
      suggesting that a functional SR Ca2+ uptake is necessary for the response to
      endogenous or exogenous NO. 4. These results, along with our previous findings of
      the dependence of i.j.ps and NO-donor hyperpolarizations on K+ channel activation
      and cyclic GMP elevation, support the hypothesis that subplasmalemmal (Ca2+)i
      elevation, via vectorial Ca2+ release from superficial SR toward the plasmalemma,
      may be an important mechanism by which NO, from NO-liberating compounds or
      released from inhibitory neurones induces relaxation and i.j.ps in opossum
      oesophagus.

PMID- 8864561
TI  - Involvement of prostaglandins in the down-regulation of allergic plasma leakage
      observed in rats undergoing pleural eosinophilia.
AB  - 1. Recent evidence has implicated eosinophils in the inhibition of allergen
      induced rat pleurisy, but the mechanism of this negative modulation is not
      completely understood. This study was undertaken in order to define the potential
      role of prostaglandins in this phenomenon. 2. Wistar rats were actively
      sensitized by subcutaneous injection of a mixture of ovalbumin and AI(OH)3 and
      challenged with an intrapleural (i.pl.) injection of ovalbumin (12
      micrograms/cavity) 14 days later. 3. Analysis of the pleural fluid effluent
      revealed a massive mast cell degranulation and plasma protein extravasation 4 h
      post-challenge. We confirmed that concurrently with selective pleural fluid
      eosinophilia caused by platelet-activating factor (PAF), the pleural cavity
      became hyporesponsive to allergen-induced protein exudation and to the parallel
      reduction in the number of intact mast cells. 4. These hyporesponsive animals
      presented a significant augmentation in the pleural effluent level of
      prostaglandin E2 (PGE2), which increased with increasing numbers of eosinophils
      in the pleural cavity. Furthermore, pretreatment with either indomethacin or
      aspirin failed to modify allergen-induced exudation but reversed the exudatory
      hyporesponsiveness associated with eosinophil recruitment. 5. Allergic exudation
      was clearly down-regulated by the following pretreatments: (i) PGE2 (10
      micrograms/cavity, i.pl.) plus rolipram (40 micrograms/cavity, i.pl.), (ii)
      misoprostol (200 micrograms kg-1, p.o.) or (iii) dibutyryl cyclic AMP (80
      micrograms/cavity, i.pl.). 6. We conclude that prostaglandins may be implicated
      in the eosinophil-mediated inhibition of allergic pleurisy, probably acting via
      cyclic AMP signalling pathway activation.

PMID- 8864562
TI  - Further evidence for the presence of cannabinoid CB1 receptors in guinea-pig
      small intestine.
AB  - 1. CP 50,556, CP 55,940, nabilone, CP 56,667, delta 9 -tetrahydrocannabinol (THC)
      and cannabinol each inhibited electrically-evoked contractions of the myenteric
      plexus-longitudinal muscle preparation of guinea-pig small intestine in a
      concentration-related manner. The IC50 values of these cannabinoids, respectively
      3.45, 3.46, 30.61, 162.94, 214.63, and 3913.5 nM, correlate well with previously
      obtained potency values for displacement of [3H]-CP 55,940 from cannabinoid
      binding sites. 2. Electrically-evoked contractions of the myenteric plexus
      longitudinal muscle preparation were also inhibited by AM 630 (6-iodo
      pravadoline) and by WIN 55,212-2 (IC50 = 1923.0 and 5.54 nM, respectively). The
      present finding that AM 630 is an agonist, contrasts with a previous observation
      that it behaves as a cannabinoid receptor antagonist in the mouse isolated vas
      deferens. 3. SR141716A produced dose-related parallel rightward shifts in the log
      concentration-response curves of CP 55,940, WIN 55,212-2, THC and AM 630 for
      inhibition of electrically-evoked contractions of the myenteric plexus
      longitudinal muscle preparation. SR141716A (1 microM) did not reverse the
      inhibitory effects of normorphine and clonidine on electrically-evoked
      contractions or potentiate the contractile response to acetylcholine. 4. Doses of
      naloxone and yohimbine that reversed the inhibitory effects of normorphine or
      clonidine on electrically-evoked contractions of the myenteric plexus
      longitudinal muscle preparation did not affect the inhibitory response to WIN
      55,212-2. 5. Electrically-evoked release of acetylcholine from strips of
      myenteric plexus-longitudinal muscle was decreased by 200 nM CP 55,940 and this
      inhibitory effect was almost completely reversed by 1 microM SR141716A.
      Acetylcholine-induced contractions were not affected by 200 nM CP 55,940. 6.
      These results support the hypothesis that guinea-pig small intestine contains
      prejunctional cannabinoid CB1 receptors through which cannabinoids act to inhibit
      electrically-evoked contractions by reducing release of the contractile
      transmitter, acetylcholine. 7. THC was found to be more susceptible to antagonism
      by SR141716A than CP 55,940 or AM 630, raising the possibility that guinea-pig
      small intestine contains more than one type of cannabinoid receptor. 8. At
      concentrations of 10 nM and above, SR141716A produced small but significant
      increases in the amplitude of electrically-evoked contractions of the myenteric
      plexus-longitudinal muscle preparation suggesting that this tissue may release an
      endogenous cannabinoid receptor agonist or that some cannabinoid receptors in
      this tissue are precoupled and that SR141716A can reduce the number of receptors
      in this state.

PMID- 8864563
TI  - Substance P and capsaicin-induced mechanical hyperalgesia in the rat knee joint;
      the involvement of bradykinin B1 and B2 receptors.
AB  - 1. Substance P (SP) and capsaicin induced a mechanical hyperalgesia when injected
      into rat knee joints. 2. The NK1 receptor antagonists CP 99994 (10-100 nmol) and
      RP 67580 (0.1-1 nmol) blocked the development of, and also reversed, SP-induced
      hyperalgesia. Capsaicin (10 nmol)-induced hyperalgesia was blocked by capsazepine
      (0.5-5 nmol). 3. Capsaicin-induced hyperalgesia was prevented and reversed by the
      NK1 receptor antagonists CP 99994 (100 nmol) and RP 67580 (1 nmol). 4. The
      bradykinin B2 receptor antagonist icatibant (5 pmol) blocked the development of
      both SP and capsaicin-induced hyperalgesia. Icatibant (100 pmol kg-1, i.v.) also
      reversed an established SP and capsaicin-induced hyperalgesia. 5. Both low dose
      SP (1 nmol) and capsaicin (1 nmol)-induced hyperalgesia were potentiated by the
      kininase II inhibitor captopril (100 micrograms). 6. The B1 receptor antagonists
      desArg9Leu8-bradykinin (BK) (0.5-5 nmol) and desArg10[Hoe 140] (5-50 pmol) only
      blocked the development of SP-induced hyperalgesia for 30 min after
      administration. desArg9Leu8-BK (10 nmol kg-1 i.v.) did not reverse an established
      SP-induced hyperalgesia. 7. Capsaicin-induced hyperalgesia was blocked by
      desArg9Leu8-BK (0.5 nmol) and this antagonist also reversed an established
      capsaicin-induced hyperalgesia. 8. Interleukin-1 receptor antagonist (IL-1ra 0.1
      microgram) reduced the development of SP-induced hyperalgesia up to 4 h after
      administration, but did not reverse an established hyperalgesia. IL-1ra (0.1
      microgram) also blocked the development of and reversed an established capsaicin
      induced hyperalgesia. 9. Indomethacin pretreatment (1 mg kg-1, s.c.) did not
      reduce the development of either SP- or capsaicin-induced hyperalgesia but
      following indomethacin-pretreatment desArg9Leu8-BK (10 nmol kg-1, i.v.) failed to
      reverse a capsaicin-induced hyperalgesia. 10. In conclusion, both SP and
      capsaicin can induce behavioural hyperalgesia when injected into the knee joint
      of rats. In addition, blockade of NK1, bradykinin B1, B2 and IL-1 beta receptors
      can substantially modulate this hyperalgesia.

PMID- 8864564
TI  - Characterization of the P2Y-purinoceptor involved in the ATP-induced rise in
      cytosolic Ca2+ concentration in rat ileal myocytes.
AB  - 1. The P2-purinoceptor subtype and the intracellular signalling mechanism(s)
      involved in the rise in the free cytosolic Ca2+ concentration ([Ca2+]i) induced
      by ATP and analogues were analyzed in myocytes isolated from the longitudinal
      muscle layer of rat ileum by means of molecular and physiological techniques. 2.
      The P2-purinoceptor expressed by ileal smooth muscle cells shared 100% amino acid
      identity with the rat P2Y1-receptor. 3. Short applications of the purinoceptor
      agonists induced a transient rise in [Ca2+]i in an all-or-nothing manner. The
      rank order of potency of the analogues of ATP and ADP, determined by measuring
      the percentage of responding cells was 2-methylthioATP = 2-chloro-ATP > ADP >
      ATP, with concentrations giving [Ca2+]i response in 50% of cells ranging between
      3 nM and 0.6 microM. The concentration-response curves to ADP and ATP were
      shifted to the right by 10 microM pyridoxal phosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS). 4. Although the rise in [Ca2+]i induced by stimulation
      of the ileal P2v-purinoceptor was inhibited by heparin (5 mg ml-1), we were not
      able to detect stimulation of phospholipase C under conditions (37 degrees C)
      where muscarinic cholinoceptor activation markedly increased inositol phosphate
      (InsP) accumulation. However, the carbachol (CCh)-induced increase in InsP
      accumulation was suppressed when the agonist was applied at 20 degrees C while a
      CCh-induced [Ca2+]i rise similar to that obtained in response to the P2
      purinoceptor agonist was still observed. 5. Our results indicate that the rat
      ileal myocytes express a PPADS-sensitive P2-purinoceptor similar to the P2Y1
      receptor subtype. Although there is no detectable increase in InsP production,
      stimulation of these receptors leads to a rise in [Ca2+]i by activation of the
      inositol 1,4,5-trisphosphate receptor-channel of the intracellular Ca2+ store,
      indicating that they couple to phospholipase C.

PMID- 8864565
TI  - Thromboxane A2 agonist modulation of excitatory synaptic transmission in the rat
      hippocampal slice.
AB  - 1. The effects of the selective thromboxane A2 (TXA2) receptor agonist I-BOP on
      neuronal excitability and synaptic transmission were studied in the CAl neurones
      of rat hippocampal slices by an intracellular recording technique. 2. Superfusion
      of I-BOP (0.5 microM) resulted in a biphasic change of the excitatory
      postsynaptic potential (e.p.s.p.), which was blocked by pretreatment with SQ
      29548, a specific antagonist of TXA2 receptors. The inhibitory phase of I-BOP on
      the e.p.s.p. was accompanied by a decrease in neuronal membrane input resistance.
      3. The sensitivity of postsynaptic neurones to glutamate receptor agonists, alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or N-methyl-D-aspartate
      (NMDA), was unchanged by I-BOP (0.5 microM) pretreatment. 4. Bath application of
      Ba2+ (0.5 mM) prevented both the I-BOP-induced reduction of the neuronal membrane
      input resistance and the blockade of e.p.s.p. induced by I-BOP. 5. Intracellular
      dialysis of the hippocampal CA1 neurones with GDP (10 mM) significantly
      attenuated the I-BOP inhibition of e.p.s.p. and membrane input resistance.
      Incubation of the slices with either pertussis toxin (PTX, 5 micrograms ml-1 for
      12 h) or cholera toxin (CTX, 5 micrograms ml-1 for 12 h) did not affect the
      biphasic action of I-BOP on the e.p.s.p. or the reduction of membrane input
      resistance induced by I-BOP. 6. Pretreatment of the slices with the protein
      kinase C (PKC) inhibitor, NPC-15437 (20 microM), abolished the biphasic
      modulation by I-BOP (0.5 microM) of the e.p.s.p. Intracellular application of a
      specific PKC inhibitor, PKCI 19-36 (20 microM), completely inhibited the I-BOP
      reduction of e.p.s.p. The specific cyclic AMP-dependent protein kinase (PKA)
      inhibitor, Rp-cyclic adenosine 3',5'-monophosphate (Rp-cyclic AMPS, 25 microM),
      had no effect on the I-BOP action. 7. In this study we have demonstrated, for the
      first time, the existence of functional TXA2 receptors in the hippocampus which
      mediate the effects of a TXA2 agonist on neuronal excitability and synaptic
      transmission. Activation of the presynaptic TXA2 receptors may stimulate the
      release of glutamate. Conversely, activation of postsynaptic TXA2 receptors leads
      to inhibition of synaptic transmission resulting from a decrease in the membrane
      input resistance of the neurones. The pre- and postsynaptic actions of the TXA2
      agonist are both mediated by PTX- and CTX-insensitive G-protein-coupled
      activation of PKC pathways.

PMID- 8864566
TI  - Recovery from TPA inhibition of receptor-mediated Ca2+ mobilization is paralleled
      by down-regulation of protein kinase C-alpha in CHO cells expressing the CCK-A
      receptor.
AB  - Digital-imaging microscopy of Fura-2-loaded Chinese hamster ovary cells, stably
      expressing the cholecystokinin-A receptor, revealed that both the C-terminal
      octapeptide of cholecystokinin (CCKB) and its analogue JMV-180, which acts as an
      agonist at the high-affinity CCK-A receptor, recruited CHO-CCK-A cells dose
      dependently in terms of receptor-mediated Ca2+ mobilization. Agonist-evoked cell
      recruitment was inhibited by short-term (10 min) pretreatment with 0.1 microM 12
      O-tetradecanoylphorbol 13-acetate (TPA). In the case of CCKB, inhibition was
      overcome with increasing of the hormone concentration. In contrast, increasing of
      the JMV-180 concentration did not reverse the inhibitory action of TPA. CHO-CCK-A
      cells gradually regained their responsiveness to JMV-180 during prolonged TPA
      pretreatment. Complete recovery was observed within 1 h following addition of
      TPA. Western blot analysis using antibodies directed against the various PKC
      isotypes revealed that recovery was paralleled by the disappearance of PKC-alpha.
      Surprisingly, short-term (10 min) TPA pretreatment virtually completely inhibited
      the formation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in response to CCKB
      concentrations at which the effect on cell recruitment was not affected by short
      term phorbol ester pretreatment. Together with the finding that JMV-180 does not
      detectably increase the cellular Ins(1,4,5)P3 content, this suggests a large
      overproduction of this second messenger by CCKB concentrations supramaximal in
      terms of cell recruitment. Again, full responsiveness was observed after long
      term TPA pretreatment. The present observations are in agreement with the idea
      that in CHO-CCK-A cells activation of PKC-alpha leads to inhibition of agonist
      evoked Ca2+ mobilization through inhibition of receptor-stimulated Ins(1,4,5)P3
      formation.

PMID- 8864567
TI  - Two different store-operated Ca2+ entry pathways in MDCK cells.
AB  - Whole cell patch clamp experiments in conjunction with Fura-2 fluorescence
      microscopy were performed to study the mechanisms of 'store-operated'
      (capacitative) Ca2+ entry. In MDCK cells, depletion of inositol 1,4,5
      trisphosphate (IP3)-sensitive Ca2+ stores activates a store-operated cation
      current (SOCC) predominantly selective for Ca2+ than for Na+ or Mn2+ [Delles C.,
      Haller T., Dietl P. A highly calcium-selective cation current activated by
      intracellular calcium release in MDCK cells. J Physiol 1995, 486: 557-569]. In
      the presence of extracellular Ca2+, thapsigargin (TG) stimulated both SOCC and a
      Ca(2+)-dependent K+ current (IK(Ca)), reflecting stimulation of store-operated
      Ca2+ entry. The Ca2+ entry blocker 1-[3-(4-methoxyphenyl) propoxyl]-1-(4
      methoxyphenyl)-ethyl-1H-imidazole HCI (SK&F96365; 30 microM) did not inhibit
      SOCC. At the same concentration, it exerted a transient partial inhibition on
      IK(Ca) activated by TG-induced Ca2+ entry. It did, however, not directly inhibit
      IK(Ca). This was demonstrated by an unchanged relationship between the cytosolic
      Ca2+ concentration ([Ca2+]i) and IK(Ca) in experiments where [Ca2+]i was measured
      under whole cell patch clamp conditions and by a lacking effect of SK&F96365 on
      IK(Ca) prestimulated by a high 'clamped' [Ca2+]i. La3+ partially, but not
      directly, inhibited the TG-induced IK(Ca) at a concentration (10 microM)
      sufficient to entirely block SOCC. La3+ and SK&F96365 in combination exerted an
      additive reduction on the TG-induced whole cell conductance (G) and completely
      blocked IK(Ca) stimulated by TG. We conclude that two Ca2+ entry pathways with
      different pharmacological and biophysical properties are involved in 'store
      operated' Ca2+ entry in MDCK cells.

PMID- 8864568
TI  - Ionomycin induced changes in intracellular free calcium in SH-SY5Y human
      neuroblastoma cells: sources of calcium and effects on [3H]-noradrenaline
      release.
AB  - In adherent SH-SY5Y human neuroblastoma cells cultured for 14 days to promote
      uptake and release of [3H]-noradrenaline, ionomycin induced a biphasic elevation
      of the intracellular [Ca2+] ([Ca2+]i). This consisted of a rapid transient
      elevation followed by a marked, persistent secondary elevation. Further study
      indicated that the peak [Ca2+]i elevation was dependent upon intracellular Ca2+
      whilst the secondary elevation was dependent upon extracellular Ca2+. This
      profile of response and dependence upon intracellular and extracellular sources
      of Ca2+ was similar to that evoked by the muscarinic agonist, methacholine but
      was independent of inositol 1,4,5-trisphosphate generation. Ionomycin also
      stimulated the release of [3H]-noradrenaline from preloaded cells. Both
      intracellular and extracellular sources of Ca2+ were needed for the full response
      and synergised to effect release. Thus, in adherent SH-SY5Y cells, ionomycin
      elevates [Ca2+]i in a complex way in a manner partly analogous to the elevation
      of [Ca2+]i by agonists of phosphoinositidase C-linked receptors. Furthermore the
      effects of [Ca2+]i elevation on [3H]-noradrenaline release by these two processes
      are similar. Such functional consequences may, however, differ under
      circumstances where the profile and source of Ca2+ for ionomycin-mediated changes
      differs to that of receptor agonists.

PMID- 8864569
TI  - Depletion of calcium stores by thapsigargin induces membrane depolarization by
      cation entry in human neutrophils.
AB  - The ability of various cations to change the electrical potential of the plasma
      membrane was examined in human neutrophils by the use of the fluorescent cationic
      dye 3,3'-dipropylthiadicarbocyanine. When the cells were suspended in 140 mM KCl,
      the fluorescence was high, indicating depolarized neutrophils. Suspension in 145
      mM N-methyl-D-glucamine chloride (NMG), replacing sodium and potassium chloride,
      resulted in hyperpolarized neutrophils. After depletion of the intracellular
      calcium stores of the NMG-suspended cells with thapsigargin and EDTA or EGTA, the
      addition of cations depolarized the neutrophils, suggesting the existence of
      pathways for cation entry. Besides Na+ and K+, several divalent cations were
      effective in the sequence: Ca2+ > Mn2+ > Ba2+ > Cd2+ > Mg2+ > Co2+ > Zn2+ > Ni2+.
      Pretreatment of the neutrophils with 0.5 or 1 mM CaCl2, resulting in loading of
      calcium stores, reduced the ability of some of the cations to depolarize the NMG
      suspended cells. From the depolarizing effects of the cations it is concluded
      that the entries of Ca2+, Mg2+, Mn2+, Ba2+, probably Co2+, to some extent Na+ and
      K+, but hardly Cd2+, Zn2+, or Ni2+, are regulated by the filling state of the
      intracellular calcium stores in human neutrophils. The store-regulated entry
      pathway may contribute to the control of the membrane potential and become active
      when the neutrophils are stimulated.

PMID- 8864570
TI  - Characterization of an oxytocin-induced rise in [Ca2+]i in single human
      myometrium smooth muscle cells.
AB  - The effect of the uterotonic pituitary hormone oxytocin on the regulation of
      intracellular calcium concentration ([Ca2+]i) was studied in single cells of a
      smooth muscle cell line derived from human non-pregnant myometrium. [Ca2+]i was
      measured with fluorescence microscopy, and by recording the activity of Ca(2+)
      activated potassium currents (IK(Ca)) on the whole cell and single channel level.
      Oxytocin induced a rapid and transient increase in [Ca2+]i that was paralleled by
      a significant increase in IK(Ca) activity. After removal of extracellular Ca2+,
      repetitive stimulation with oxytocin did not alter the [Ca2+]i transients
      initially; however, their amplitude became progressively smaller and the response
      was eventually abolished completely, indicating that oxytocin increased [Ca2+]i
      by release of Ca2+ from intracellular stores. Nifedipine did not alter the
      oxytocin-induced [Ca2+]i-transients suggesting that oxytocin failed to activate
      Ca2+ entry through voltage-operated Ca2+ channels. Thapsigargin abolished the
      oxytocin-induced [Ca2+]i transient. Caffeine alone had no effect on [Ca2+]i,
      however it diminished the oxytocin-induced [Ca2+]i transients. Ryanodine did not
      affect the oxytocin response indicating that these cells lack release of Ca2+
      from the ryanodine receptor release channel. These results demonstrate that
      oxytocin elicited [Ca2+]i transients predominantly through Ca2+ release from
      thapsigargin-sensitive stores, presumably by activating an inositol 1,4,5
      trisphosphate dependent pathway.

PMID- 8864571
TI  - Ca2+ signaling in endothelial cells stimulated by bradykinin: Ca2+ measurement in
      the mitochondria and the cytosol by confocal microscopy.
AB  - In this study we have monitored the change of intracellular Ca2+ concentrations
      in the cytosol ([Ca2+]c) and the mitochondria ([Ca2+]m) of single bovine
      endothelial cells following treatment with bradykinin (BK). Using laser scanning
      confocal microscopy, we have found that the Ca2+ indicator, Fluo-3, is
      compartmentalized in the mitochondria of endothelial cells loaded with Fluo-3/AM.
      After BK stimulation, the pattern of Ca2+ increase in the cytosol is different
      from that in the mitochondria. The amplitude of the Ca2+ rise in the mitochondria
      is higher than that in the cytosol. Further analysis using rapid scanning
      measurements indicates that the [Ca2+]c increase is very fast after BK addition
      and reaches a maxima level within 400 ms. In contrast, the [Ca2+]m increase
      appears to be biphasic with an initial rapid increase (concomitant with the
      [Ca2+]c increase) followed by a slower [Ca2+]m increase before reaching a maximal
      level (within 5 s of BK treatment). The differential Ca2+ signaling pattern
      between the cytosol and the mitochondria suggests that the intracellular Ca2+
      concentrations needed to regulate various Ca(2+)-dependent enzymes located in
      these two compartments are different during BK-induced endothelial cell
      activation.

PMID- 8864572
TI  - The calcium-binding protein calretinin-22k, an alternative splicing product of
      the calretinin gene is expressed in several colon adeno carcinoma cell lines.
AB  - An alternatively spliced mRNA for the calcium-binding protein calretinin (CR) is
      present in the colon adenocarcinoma cell line WiDr. As a consequence of a frame
      shift, the resulting protein, calretinin-22k (CR-22k), consists of the first 178
      amino acids of calretinin followed by a carboxy-terminal peptide of 14 amino
      acids that is not present in full-length calretinin. Antibodies specific for this
      C-terminal region have been generated by 2 different methods. A peptide
      corresponding to the specific C-terminal region of CR-22k was either chemically
      synthesized and coupled to a carrier protein or was expressed in Escherichia coli
      as a carboxyterminal fusion to a carrier protein applying recombinant techniques.
      Both antisera produced in rabbits were tested in Western blots and immuno
      histochemical experiments. The antisera recognized human recombinant CR-22k
      overexpressed in E. coli, but not fulllength calretinin and stained fixed WiDr
      cells. The presence of CR-22k was also confirmed in the colon cell lines CO115/3
      in which mRNA coding for CR-22k mRNA coding for CR-22k mRNA is present as well as
      in the lines COLO205 and LS-180, all of which also express full-length
      calretinin. Although the intracellular distribution of CR-22k and CR are similar
      as evidenced by immunohistochemical stainings, CR-22k is preferentially localized
      in the nucleus in the cell lines LS-180 and Co115/3 suggesting potentially
      different roles for the two proteins.

PMID- 8864573
TI  - A method for measuring sarcoplasmic reticulum calcium uptake in the skeletal
      muscle using Fura-2.
AB  - We have presented an assay for measuring the rate of sarcoplasmic reticulum (SR)
      Ca2+ uptake and Ca2+ release in skeletal muscle homogenates using the fluorescent
      Ca2+ probe Fura-2. Using this assay, we investigated the effects of an elevated
      temperature (40 degrees C) and lowered pH (6.8), two factors proposed to be
      involved in skeletal muscle fatigue, on SR Ca2+ uptake. The EDL muscle was found
      to have a higher rate of Ca2+ uptake than the soleus (34%). Exposure of the
      muscles to a raised temperature, but not a reduced pH, resulted in a reduction in
      the rate of Ca2+ uptake in both the EDL and soleus homogenates. This uptake
      process was blocked by cyclopiazonic acid (CPA) a specific inhibitor of the major
      transport protein of the sarcoplasmic reticulum, the Ca(2+)-ATPase. Calcium
      release was induced using AgNO3 after loading of the vesicles during the uptake
      process. It was found that AgNO3 was only effective in producing Ca2+ release in
      the EDL muscles. The soleus muscles did not release Ca2+ under varying [Mg2+] or
      with Hg2+ substitution for Ag+, suggesting that fast- and slow-twitch muscle
      fibres require different conditions for maximum Ca2+ release, or that different
      isoforms of the Ca2+ release channels are present in the different fibres.

PMID- 8864574
TI  - Calreticulin: how many functions in how many cellular compartments? Como, April
      1996.

PMID- 8864575
TI  - Calcium binding proteins in normal and transformed cells, Perugia, May 1996.

PMID- 8864576
TI  - Spondyloarthropathies-spondylarthropathies.
AB  - A committee of the European League Against Rheumatism has recommended that the
      term spondylarthropathy (without the letter "o" in the middle) should be avoided
      and is of the opinion that the use of the radical spondylo makes it clear that
      spondyloarthropathy is a composed word to refer to a disease that affects the
      spine and (peripheral) joints. The committee points out that the term
      spondyloarthritis (plural is spondyloarthritides) is more accurate because it
      means association of spondylitis with (peripheral) arthritis. The known number of
      subtypes of HLA-B27 continues to grow. The latest two additions are HLA-B*2710,
      identified in an American Caucasian family with spondyloarthropathy, and HLA
      B*2711, discovered in a healthy Japanese person.

PMID- 8864577
TI  - Clinical and epidemiologic aspects of ankylosing spondylitis and
      spondyloarthropathies.
AB  - In the past decade the concept of spondyloarthropathy has become well
      established, and appropriate classification criteria have been developed. Now it
      is time to better define the terms in common use in order to facilitate
      scientific communication. Recently, new therapeutic approaches have been tested,
      but the design of some of these studies is weak. Clearly, the outcome of
      ankylosing spondylitis and spondyloarthritis is multidimensional. A number of new
      instruments for the assessment of ankylosing spondylitis are now available, but
      there is a need for core sets of outcome measures appropriate for the different
      settings in which assessment is done. Although criteria intended for use in
      epidemiologic studies might be useful in daily clinical practice to establish a
      diagnosis, improved recognition of the different elements of ankylosing
      spondylitis and spondyloarthritis requires more "problem orientation" and less
      "disease orientation."

PMID- 8864578
TI  - The sacroiliac joint in the spondyloarthropathies.
AB  - The term spondyloarthropathy (SpA) describes and defines a group of related
      inflammatory joint disease that share characteristic clinical features and a
      unique association with the major histocompatibility complex class I molecule HLA
      B27. Five subgroups can be differentiated: ankylosing spondylitis, reactive
      arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel
      disease, and undifferentiated SpA. The sacroiliac joints are centrally involved
      in the SpA, most clearly and pathognomonic in ankylosing spondylitis, in which
      most patients are affected early in the disease. Overcoming some of the
      diagnostic difficulties of early sacroiliitis, dynamic magnetic resonance imaging
      was shown to visualize both acute and chronic changes in the sacroiliac joints.
      The inflammation in the sacroiliac joints in patients with SpA was recently
      examined in more detail; using immunohistology and in situ hybridrization, T
      cells, macrophages, and various cytokines were found in infiltrates. Biopsy
      specimens were obtained under guided computed tomography, and in the same study,
      intra-articular corticosteroid treatment was successfully undertaken. Further
      investigation of such biopsy specimens showed the absence of DNA of reactive
      arthritis-associated bacteria. The pathogenesis of the SpA and the reason for the
      tropism for the sacroiliac joints is still obscure. The nature of the relation of
      the genetic background of SpA to initially triggering bacterial infections
      remains to be established. In chronic disease, autoimmune mechanisms might be
      more important.

PMID- 8864579
TI  - Management of spondyloarthropathies.
AB  - Better understanding of the etiopathogenic mechanisms and increasing recognition
      of the natural course of the spondyloarthropathies are leading to a more rational
      therapeutic approach to several of the disorders included within this large group
      of arthritides. Our traditional therapeutic approach to these conditions is being
      challenged, and a more aggressive therapeutic regimen is being advocated in a
      manner not too much different from that advocated for the treatment of rheumatoid
      arthritis. Combination therapy with either methotrexate and sulfasalazine or
      methotrexate and cyclosporine is being used more often and earlier, particularly
      in psoriatic arthritis. An issue, however, that remains unresolved is the proper
      use of antibiotic therapy.

PMID- 8864580
TI  - HLA-B27 structure, function, and disease association.
AB  - The polymorphism of HLA-B27 alleles is located in the peptide-anchoring motif. In
      recent years, fundamental insights have been made into the molecular aspects of
      HLA-B27-restricted presentation. Subtle differences in peptide binding fine
      specificity are especially interesting for closely related HLA-B27 alleles that
      have differential association with ankylosing spondylitis. Bacterial infection
      has been suggested to play a role in the pathogenesis of HLA-B27-associated
      disease. Remarkable progress has been made in identifying peptides derived from
      bacteria that can be presented by HLA-B27. Despite the mechanisms proposed to
      explain B27-associated diseases, there are no clear correlations between peptide
      sequence, differential binding to B27 subtypes, and recognition by peptide
      specific T cell receptors. Furthermore, new transgenic models have now been
      developed that we hope will allow a clearer view of the function of B27 and the
      mechanisms involved in the pathogenesis of spondyloarthropathies.

PMID- 8864581
TI  - Etiopathogenesis and biochemical and immunologic evaluation of
      spondyloarthropathies.
AB  - Spondyloarthropathies are closely related to genetics and certain bacteria. The
      ability to study these relationships at the molecular level has revealed
      increasing complexity in the interplay of genetics, microbes, and the diseases.
      Advances have been made in the genetics at the major histocompatibility complex.
      The mediators of inflammation in spondyloarthropathies have begun to be
      elucidated. The role of bacterial pathogenesis in the joints is being better
      defined and implies that viable organisms are in the joints of persons with
      reactive arthritis at some point in the illness. Disease-prone transgenic animals
      have been developed that demonstrate the need for an environmental trigger. The
      nature of the interaction of HLA-B27 with the microbes associated with the
      disease is unclear. Several hypotheses are being rigorously investigated.

PMID- 8864582
TI  - Infectious arthritis and immune dysfunction.

PMID- 8864583
TI  - Septic bone and joint infections.
AB  - Three main trends are apparent in the study of septic bone and joint infections.
      First, molecular microbiology has advanced our understanding of how
      microorganisms find structures in the joints and connective tissue on which to
      adhere, reproduce, and exert an infectious process. Second, modern diagnostic
      methods such as DNA hybridization and polymerase chain reaction are facilitating
      the identification of causative microbes. Finally, unusual and previously unknown
      causes of infection are being identified in joints and bone, often through a time
      consuming search in which modern diagnostic techniques may be of valuable help.

PMID- 8864584
TI  - Lyme disease.
AB  - In the United States, there was an increase in the number of reported cases of
      Lyme disease in 1994 compared with previous years. The majority of cases occurred
      in the Northeast and Midwest, which are areas with established foci of Borrelia
      burgdorferi. Advances in the understanding of the epidemiology and ecology of
      ixodes ticks, the established vector for transmission of Lyme disease, provided
      strategies for reducing tick populations and the risk of acquiring disease.
      Dissemination of B. burgdorferi from the site of a tick bite likely occurs, in
      part, via attachment to host plasmin and subsequent degradation of glycoproteins.
      Analysis of T cell immune responses in mice contributed to our understanding of
      differences in disease susceptibility. Vaccination of patients with previous Lyme
      disease has been found to be safe, and clinical trials of vaccine efficacy are
      currently under way.

PMID- 8864585
TI  - Reactive arthritis.
AB  - During the past year, new information has been obtained regarding the
      pathogenetic process in reactive arthritis. Characterization of the triggering
      microbes as well as of their interaction with T cells and other host components
      has brought us closer to achieving a comprehensive picture of the events leading
      from infection to reactive arthritis. Efforts are ongoing to define clinically
      applicable diagnostic criteria. It is becoming apparent that chronic forms of the
      disease are not uncommon.

PMID- 8864586
TI  - Viral arthritis.
AB  - Viral infections can present with different patterns of joint and soft tissue
      involvement, and the etiologic role of viruses in various rheumatic diseases is a
      subject of continued great interest. Recently, new immunoenzymatic assays have
      brought a better understanding of the relationship between hepatitis C virus
      serotypes and their immunologic manifestations. Our knowledge of the consequences
      of parvovirus B19 infection has broadened to include the variable clinical
      spectrum the role of inflammatory cytokine production in parvovirus-induced
      arthritis, a postulated causative role for B19 in rheumatoid arthritis, and a
      negative association between parvovirus and Still's disease as well as chronic
      fatigue syndrome. New, specific antibodies to nonstructural protein NS-1 in
      parvovirus B19-associated arthritis have been detected. Arthritis related to
      hepatitis B virus vaccination or measles and mumps vaccination was also reported.
      The papers reviewed here demonstrate the continuing efforts in defining the
      etiopathogenesis of virus-induced rheumatic diseases.

PMID- 8864587
TI  - Rheumatic aspects of acquired immunodeficiency syndrome.
AB  - Infection with HIV-1 continues to provide important insights into autoimmunity
      and rheumatic diseases. Studies on the mechanisms of B cell hyperreactivity in
      HIV-infected persons suggest a primary role for B cell complement receptor
      engagement by circulating immune complexes in the production of autoantibodies.
      Delineation of the epitopes recognized by antiphospholipid antibodies induced by
      HIV-1 offers insight into the mechanism of thrombosis associated with
      antiphospholipid antibodies found in the rheumatic diseases. Several reports have
      documented the coexistence of rheumatoid arthritis and HIV-1 infection,
      emphasizing the importance of both T cell-dependent and -independent mechanisms
      in the pathogenesis and clinical manifestations of rheumatoid arthritis. The
      mechanisms of host-virus interactions leading to rheumatic disease continue to be
      studied in HIV-infected persons with diffuse infiltrative lymphocytosis syndrome,
      a disease in which host immunogenetics appear to be the determining factor, and
      in persons with polymyositis. In both diseases, tissue cell damage appears to be
      a consequence of the host immune response to viral proteins present within
      macrophages in the target tissues. Because similar mechanisms appear to be
      involved in polymyositis associated with HTLV-I (human T cell lymphoma virus type
      I) infection, studies into a primate model of polymyositis induced by HTLV-I may
      be particularly informative. The clinical management of HIV-associated
      arthritides remains difficult, likely reflecting the role of HIV-1 gene products
      in initiating or amplifying inflammatory joint disease. Two anti-inflammatory
      drugs frequently used to treat patients with rheumatic diseases, indomethacin and
      hydroxychloroquine, can directly inhibit HIV-1 replication and may provide a
      rational therapeutic approach in combination with conventional antiviral agents.

PMID- 8864589
TI  - Male osteoporosis.
AB  - The clinical spectrum of osteoporosis is similar in men and women. There are,
      however, gender differences in skeletal development, age-related bone loss, and
      secondary causes of osteoporosis. The magnitude of the problem of male
      osteoporosis, factors related to bone mass acquisition and bone loss, and the
      principal risk factors for osteoporosis in men are discussed here. In addition,
      treatment strategies are reviewed.

PMID- 8864590
TI  - Relationship between osteoporosis and arthritis and effect of corticosteroids and
      other drugs on bone.
AB  - Patients with inflammatory arthritides such as rheumatoid arthritis develop both
      localized and generalized osteoporosis and have an increased risk of fracture.
      Bone loss can occur early and is directly related to the inflammatory process as
      well as to the indirect effects of arthritis on physical activity. Corticosteroid
      induced osteoporosis remains a common and important problem in rheumatic disease,
      but controversy continues about the relative safety of "low-dose" corticosteroid
      therapy in regard to effects on bone, which should be weighted against the
      beneficial effects of controlling synovitis and minimizing functional impairment.
      Further studies are needed to evaluate therapies for glucocorticoid-induced
      osteoporosis, but prophylaxis or treatment with calcitriol, the active form of
      vitamin D, or the bisphosphonates shows considerable promise.

PMID- 8864591
TI  - Bone density and quality measurement using ultrasound.
AB  - Techniques for measuring bone mineral density have been widely accepted for the
      diagnosis and management of osteoporosis. These techniques are clinically
      feasible, and their fracture prediction capability has been proven in numerous
      studies. However, it has been demonstrated that bone strength and fracture risk
      are affected not only by the density of bone but also by other skeletal features
      including bone composition and microarchitecture. Available techniques for
      measuring bone mineral density have some disadvantages because they offer limited
      ability to assess bone quality, are relatively expensive, and use ionizing
      radiation.

PMID- 8864592
TI  - Effect of physical activity on bone mass.
AB  - Maintenance of bone mass depends on several factors, including proper level of
      physical activity, hormones, and nutrition. Prescribing effective weight-training
      and weight-bearing exercise programs for improving bone mass is highly desirable.
      Specificity of each exercise program can contribute to an increment or reduction
      of bone mass. Cessation of physical activity induces rapid metabolic bone
      changes, although the effects on bone mass take time to develop. Therefore,
      weight-bearing and periodic high-intensity loading exercises are recommended for
      maintenance of bone mass in the spine and lower extremities. Patients who endure
      a period of immobility such as prolonged bed rest should resume their daily
      activities in addition to supervised exertional exercises. While research
      continues in an effort to find ways to increase bone mass despite aging and
      negative genetic factors, more focus can be given to building a solid skeletal
      foundation through good nutritional and exercise habits developed early in life.

PMID- 8864594
TI  - Spondyloarthropathies.

PMID- 8864593
TI  - Clinical use of bisphosphonates.
AB  - The bisphosphonates (formerly known as diphosphonates) constitute a recently
      developed class of drugs for use in a variety of diseases of bone and calcium
      metabolism. Developed in the past three decades, only a few compounds of this
      large family of drugs are now commercially available for various therapeutic
      indications that vary broadly, from country to country. The clinical use of
      bisphosphonates is based on their ability to inhibit bone resorption. Thus, their
      main indications concern diseases with high bone remodeling, such as Paget's
      disease of bone, osteoporosis, metastatic bone diseases, and malignant and
      nonmalignant hypercalcemia. Their other main action is to inhibit bone formation;
      the ratio of inhibition of bone resorption to inhibition of bone formation varies
      according to the compounds. This ratio is less favorable for the first available
      bisphosphonates, such as etidronate. New bisphosphonates are more and more potent
      and possess a safer ratio. With their increasing power, there could be some risk
      of freezing bone remodeling, but so far this fearful complication has not yet
      been observed.

PMID- 8864595
TI  - Infectious arthritis and immune dysfunction.

PMID- 8864596
TI  - Metabolic bone disease.

PMID- 8864597
TI  - Children and medicine: love and responsibility.

PMID- 8864598
TI  - Childhood dermatitis in the tropics: with special emphasis on infective
      dermatitis, a marker for infection with human T-cell leukemia virus-I.

PMID- 8864599
TI  - Mucha-Habermann disease and its febrile ulceronecrotic variant.
AB  - In 1916 Mucha and in 1925 Habermann reported an acute form of pityriasis
      lichenoides characterized by the abrupt onset of papulovesicular eruptions and
      gave the name, pityriasis lichenoides et varioliformis acuta (PLEVA) or Mucha
      Habermann disease (MH). In 1966, Degos reported a rare febrile ulceronecrotic
      variant of MH. MH occurs mainly in young adults, while febrile ulceronecrotic
      Mucha-Habermann's disease (FUMHD) occurs more frequently in children. The
      etiology of MH remains obscure, but it may be the result of a hypersensitivity
      reaction to an infectious agent. Although clinical and histologic features of the
      disease in children are similar to those of adults, more diseases need to be
      differentiated in pediatric patients. In addition, a number of effective
      therapeutic options in adults with MH are unsuitable for use in pediatric
      patients, to whom beginning with oral antibiotics, usually erythromycin, is
      recommended. A summary of previously reported fifteen cases with FUMHD, including
      our case, is listed.

PMID- 8864600
TI  - Eosinophilic pustular folliculitis (Ofuji disease) in a child.
AB  - Eosinophilic pustular folliculitis (EPF) has been described mostly in adults from
      Japan. From the few reports of children with EPF it is clear that the disease
      displays the characteristic features, with some clinical differences compared to
      EPF in adults. We describe the case of an 8-year-old boy with multiple vesicles,
      pustules, and erythema multiforme-like lesions on the trunk and lower
      extremities. Results of histopathologic examination revealed subcorneal and
      intraepidermal pustules, and an inflammatory infiltrate consisting of lymphocytes
      and eosinophils mainly with a perifollicular distribution. The patient also had
      impaired chemotaxis, IgG3 subclass deficiency, and elevated IgE levels.

PMID- 8864601
TI  - Childhood scleroderma and its peculiarities.
AB  - Based on a very large series of childhood scleroderma followed for more than ten
      years, the authors describe various subsets, which, in several aspects, differ
      significantly from the adult forms. Of special importance is a higher prevalence
      of linear scleroderma resulting in deformities and disabilities, as well as
      impairment of bone development in facial hemiatrophy. The immune abnormalities
      and vascular involvement leading to fibrosis are presented as the basic events in
      the pathogenesis. Critical discussion on a possible transitional form between
      localized and systemic disease and visceral involvement in cutaneous forms is
      followed by clinically applicable laboratory studies and management, including
      new therapeutic modalities.

PMID- 8864602
TI  - Erythema toxicum neonatorum.
AB  - Erythema toxicum neonatorum is a common finding of unknown etiology affecting
      healthy newborn children, particularly those born at term. It is seen in the
      first days of life, but rarely at birth. Infants with it often have sterile
      papulopustules containing a predominance of eosinophils. It is important to
      distinguish from other cutaneous eruptions of neonates, some of which are
      serious.

PMID- 8864603
TI  - Pseudoxanthoma elasticum and pregnancy.
AB  - Reports of complications of pseudoxanthoma elasticum occurring during pregnancy
      have dissuaded some women with the disorder from attempting to conceive for fear
      of exacerbating the disease. The actual risks of serious complications during
      pregnancy, however, may be overstated. We report a 40-year-old woman with
      pseudoxanthoma elasticum who delivered a healthy male infant after an uneventful
      pregnancy. At the time of delivery, the placenta was noted to be heavily
      calcified. The effects of pregnancy on pseudoxanthoma elasticum and the effects
      of maternal pseudoxanthoma elasticum on a developing fetus are reviewed, with a
      review of the relevant medical literature.

PMID- 8864604
TI  - Progressive hemifacial atrophy: ten-year observation of a case.
AB  - The authors describe the case of a 14-year-old girl who experienced progressive
      hemifacial atrophy at the age of three-and-a-half years. The patient's early age
      at appearance of the condition resulted not only in atrophy of skin, subcutaneous
      tissue, and muscles, but also in very severe deformation of the right side of the
      face due to disorders in growth of cartilaginous and osseous tissue. Changes in
      her brain case and craniofacial skeleton included enophthalmos, underdevelopment
      of the eyelids, nose, hard plate, and dental process of the jaw including the
      premolar teeth, and a lack of the second molar. These changes caused an irregular
      line of bite. The differential diagnosis excluded hemifacial microsomy and
      sclerodermal hemifacial atrophy.

PMID- 8864605
TI  - Generalized lichen nitidus: a case report.
AB  - We report the case of a 6-year-old boy with disseminated papular lesions.
      Clinical and histopathologic examinations confirmed the diagnosis of lichen
      nitidus. There was no improvement during a three-year observation period, despite
      various methods of treatment. In the fourth year, we observed spontaneous
      resolution of the skin lesions after sun exposure in the summer.

PMID- 8864606
TI  - Juvenile xanthogranuloma beneath a fingernail.
AB  - A case of a child with juvenile xanthogranuloma beneath the fingernail is
      presented. The interest of this case is the uncommon location.

PMID- 8864607
TI  - Contact allergy in children.
AB  - With a view to determining the frequency of contact allergy in children, a group
      of 100 subjects 5 to 15 years of age with various dermatoses was examined. The
      study group included children with allergic dermatoses (atopic dermatitis,
      eczema, and others) as well as nonallergic skin diseases (alopecia areata,
      psoriasis, vitiligo). The frequency of contact allergy occurrence in the
      individual groups has been determined. Contact allergy occurred the most
      frequently in children with various forms of eczema (60 percent), the least
      frequently in those with nonallergic dermatoses (32 percent). Children with
      eczema most often displayed a polyvalent allergy. Most frequently, positive patch
      test reactions occurred with potassium dichromate (in 21 percent of children),
      with cobalt chloride (in 11 percent), and with neomycin sulfate (in 10 percent).

PMID- 8864608
TI  - Significance and management of congenital malalignment of the big toenail.
AB  - Often misdiagnosed, congenital malalignment of the big toenail is not an uncommon
      condition. It consists of a lateral deviation of the long axis of nail growth
      relative to the distal phalanx. This would be of minor importance if it were not
      for local complications that may arise in infancy and adulthood. Some cases of
      this inherited dysplasia have demonstrated a tendency to spontaneous improvement.
      Therefore, photographic surveys should be made at regular intervals to monitor
      the need for possible surgery.

PMID- 8864609
TI  - Coal tar, pine tar and sulfonated shale oil preparations: comparative activity,
      efficacy and safety.
AB  - BACKGROUND: Tar and sulfonated shale oil preparations are used in the treatment
      of a variety of inflammatory skin diseases, including psoriasis vulgaris; due to
      the high polycyclic aromatic hydrocarbon (PAH) content of tars, a possible
      relationship with cancer in humans has been postulated. On the other hand, the
      purity of sulfonated shale oils concerning PAHs guarantees a good tolerability
      during dermatologic therapy. AIM: In this review, it is attempted to compare
      activity, efficacy and safety of coal tar, pine tar and sulfonated shale oil
      preparations which currently play a role in dermatologic treatment. RESULTS AND
      CONCLUSIONS: Primary sources of PAHs in the normal human environment are forest
      fires, cigarette smoke and combustion of fossil fuels for heating and energy.
      Thermal processing of fossil substances is also required for the production of
      tars and sulfonated shale oils. Due to individual manufacturing techniques, tars
      and sulfonated shale oils differ completely in their chemical composition. Still,
      sulfonated shale oils are often falsely grouped as tars because of their related
      origin and similar dermatologic indications. There is at least limited evidence
      of the activity and efficacy of various tars as well as sulfonated shale oil
      preparations in different frequent inflammatory skin diseases. This includes
      psoriasis vulgaris and atopic eczema of glabrous as well as hairy skin. There is
      still some concern about the long-term tolerability of tar preparations at least
      in some contexts. This, however, does not apply to sulfonated shale oil
      preparations. Consequently, at least their use should still be considered a
      rational drug treatment in dermatology.

PMID- 8864610
TI  - Clinical features of systemic lupus erythematosus in men. Characteristics of the
      cutaneous manifestations.
AB  - BACKGROUND: Cutaneous manifestations of systemic lupus erythematosus (SLE) in men
      have not been precisely investigated. OBJECTIVE: The purpose of this study is to
      define the clinical features of SLE in men, focusing on skin lesions. METHODS:
      The clinical and laboratory manifestations of 28 male and 111 female patients
      were compared. RESULTS: Widespread discoid lupus erythematosus (DLE) and papular
      and nodular mucinosis (PNM) were significantly more common in men than in women.
      Serum sex hormone levels were within the normal range in all make patients
      examined. CONCLUSION: This study suggests that gender differences exist in SLE
      and that male patients tend to present with atypical cutaneous manifestations.

PMID- 8864611
TI  - Cutaneous reactions to alimentary tract medications: results of a seven-year
      surveillance program and review of the literature. Gruppo Italiano Studi
      Epidemiologici in Dermatologia (GISED).
AB  - BACKGROUND: No systemic review of skin reactions to alimentary tract medications
      is available in the literature. OBJECTIVE: We reviewed the reactions to
      alimentary tract medications reported to the surveillance system of the Italian
      Group for Epidemiologic Research in Dermatology (GISED). METHODS: Between January
      1988 and December 1994, 202 dermatologists in Italy reported to the coordinating
      center for GISED all the adverse reactions they observed during prespecified 2
      month monitoring periods. Reactions classified under ATC codes A02-A04, A06, A07
      and A09 were used for this analysis. RESULTS: Of 2,789 reactions, 48 were
      attributed to alimentary tract medications. Urticaria/angioedema and exanthemas
      accounted for about 70% of these reactions. Fixed eruptions and lichenoid
      dermatitis accounted for a large part of the remaining reactions. Antiulcers and
      antiemetics appeared remarkably safe. CONCLUSION: Our data are reassuring with
      regard to the cutaneous reaction profile of several drugs taken for diseases of
      the alimentary tract.

PMID- 8864612
TI  - Sensitizations to allergens of the European standard series at the Department of
      Dermatology in Zurich 1990-1994.
AB  - BACKGROUND: For planning and evaluation of preventive activities against contact
      dermatitis, it is important to detect trends in contact sensitization. OBJECTIVE
      AND METHODS: We performed a computer-aided analysis of the patch test results of
      5,565 patients tested with the European standard allergens consecutively from
      1990 to 1994 in our patch test clinic. RESULTS: The male/female ratio was 42.4/
      57.6%. Sixty-one percent of the patients were < 45 years. Hands, face and lower
      legs were the major localizations of eczema. The largest occupational groups were
      office workers (21%), houseworkers and cleaning personnel (18%) and pensioners
      (10%). The highest sensitization rates were found for nickel (18.5%) and
      fragrance mix (9.6%). An increase of sensitizations to fragrance mix and balsam
      of Peru in both sexes and a decrease in nickel and cobalt sensitizations for
      females and potassium dichromate reactions for males were observed. CONCLUSION:
      Our data show considerable changes in the frequency of contact sensitizations
      that warrant further analytic studies.

PMID- 8864613
TI  - Progressive systemic sclerosis associated with multiple mononeuropathy.
AB  - BACKGROUND: Progressive systemic sclerosis (PSS) is a chronic connective tissue
      inflammatory disease which commonly attacks the skin and the visceral organs, but
      rarely the peripheral nervous system. OBJECTIVE: The aim of this study was to
      investigate PSS accompanied by peripheral neuropathy clinically,
      electrophysiologically and pathologically from a sural nerve biopsy. METHODS: Two
      women suffering from PSS but without any other collagen disease were studied.
      Both patients developed peripheral neuropathy with multiple mononeuropathy of the
      limbs, and in one woman, in the trunk as well. RESULTS: A biopsy of the sural
      nerve revealed axonal and myelin segmental degeneration, loss of large myelinated
      fibers and an increase of collagen fibers, but there was no evidence of
      vasculitis. An electron microscopic examination revealed degenerated axons,
      disrupted myelin sheaths and multilayered basal lamina in the capillaries.
      CONCLUSION: Mononeuropathy in PSS suggests that ischemic neuropathy may be
      related to the immune-mediated vasculopathy.

PMID- 8864614
TI  - 'Normolipidemic' tendinous and tuberous xanthomatosis.
AB  - BACKGROUND: Multiple tendinous and tuberous xanthomas are characteristically
      associated with hyperlipidemic states. However, normolipidemic tendinous and
      tuberous xanthomas have been reported in the literature, with normal levels of
      cholesterol, cholestanol and plant sterols. OBJECTIVE AND METHOD: To delineate
      the disorder and to suggest its likely origin, a case of apparently
      normolipidemic severe tuberous and tendinous xanthomatosis was studied. Several
      lipoprotein and lipid analyses, clinical tests and histological studies were
      performed over a period of 5 years in the propositus and his family. RESULTS: At
      the first lipid analysis, no quantitative or qualitative alterations of the
      lipoprotein fractions or of the apoproteins AI, B, CII, CIII, E were detected in
      the propositus and xanthomatosis was classified as normolipidemic. During the
      follow-up, the patient showed a nonconstant hypertriglyceridemia and/or
      hypercholesterolemia associated with the presence of small and dense VLDL and
      LDL. An increase in apo-B was observed. There was an unusual quantity of
      conjugated dienes of arachidonic acid in the plasma and in the LDLs of the
      patient, present only in small traces in the control population. The family study
      and the long follow-up of the lipid analysis of the propositus were compatible
      with the diagnosis of familial combined hyperlipidemia. CONCLUSION: Our data
      highlight the importance of a critical review of studies regarding normolipidemic
      xanthomatosis, since only after an extensive follow-up and sequential analyses of
      lipoprotein fractions is it possible to exclude the presence of time variables
      and complex lipoprotein abnormalities.

PMID- 8864615
TI  - Skin risk assessment of metalworking fluids: a survey among Swiss suppliers.
AB  - BACKGROUND: Metalworking fluids (MWF) are the most important cause of hand
      dermatitis in the metal industry. The substitution of noxious products by less
      aggressive MWFs is therefore an important measure to reduce the incidence of hand
      eczema in this type of industry. In order to do so, producers and suppliers have
      to evaluate the skin risk of such products by predictive allergenicity and
      irritancy testing. OBJECTIVE: The aim of the study is to evaluate if predictive
      testing is performed in MWF products that are currently offered in the Swiss
      market and what kind of tests are applied. METHODS: A questionnaire was sent to
      11 Swiss MWF suppliers in order to collect information on the actual practice of
      skin risk testing. RESULTS: Nine of 11 suppliers returned the questionnaire. Five
      suppliers report some kind of allergenicity testing in some of the products.
      Seven companies test for irritancy by a single application method, but only two
      perform cumulative irritancy testing in some products. The methods of testing
      (animal, human, field studies) vary greatly among the different companies.
      CONCLUSION: It is concluded that the practice of predictive testing for
      sensitization and irritancy of MWF is unsatisfactory and does not allow the user
      to compare products based on their skin risk. Occupational dermatologists should
      strive for standardization of MWF testing including so far scarcely performed
      repeated insult tests.

PMID- 8864616
TI  - Pigmented and hyperkeratotic napkin dermatitis: a liquid detergent irritant
      dermatitis.
AB  - BACKGROUND: Napkin or diaper dermatitis (DD) is an inflammatory cutaneous
      eruption limited to the diaper area and common in the first 2 years of life. A
      number of clinical variants of DD have been identified. OBJECTIVE: We report a
      new variant of DD characterized by papyraceous skin, brownish discoloration and
      predilection for the depth of folds. METHODS: 15 infants and toddlers affected by
      this peculiar type of DD were evaluated regarding duration, localization,
      morphology and evolution of their dermatosis. RESULTS: This variant of DD was
      mainly confined to the depth of inguinal and gluteal folds and invariably
      associated with severe xerosis with papyraceous and glazed skin. The patients
      were healthy and asymptomatic and all laboratory investigations performed were
      normal. All patients were frequently changed and thoroughly washed with synthetic
      detergents with acid pH. DD improved rapidly with reduced frequency of washing
      and discontinuation of liquid detergents. CONCLUSIONS: We conclude that this
      condition is a type of irritant contact dermatitis from excessive use of lipid
      acid detergents.

PMID- 8864617
TI  - Out-patient treatment of atopic dermatitis with crude coal tar.
AB  - BACKGROUND: Patients with atopic dermatitis benefit from treatment with crude
      coal tar. We started a program for the treatment of patients with atopic
      dermatitis in an out-patient facility using intermittent applications of crude
      coal tar. OBJECTIVE: To study the efficacy and feasibility of an out-patient
      regimen using crude coal tar in atopic dermatitis. METHODS: We treated 18
      patients in the out-patient setting. A trained nurse and after thorough
      instruction the patients themselves at home applied crude coal tar in a zinc
      paste 2 or 3 times a week. We studied the improvement by visual scoring and
      compared the results with patients treated with daily applications at the in
      patient department. RESULTS: The improvement was comparable at the end of the
      treatment period for both settings. The treatment period, however, was longer for
      the patients treated in the out-patient setting. CONCLUSION: The out-patient
      programme proved to be an efficacious and a well-appreciated approach.

PMID- 8864618
TI  - A case of Cobb syndrome associated with lymphangioma circumscriptum.
AB  - Cobb syndrome describes the association of a spinal angioma and a cutaneous
      angioma such as nevus flammeus or angiokeratoma of the corresponding dermatome. A
      23-year-old Korean female showed spiral cord angiomas and segmentally distributed
      nevus flammeus of corresponding dermatomes (Th5-Th2). Interestingly she had a
      lymphangioma circumscriptum in the same dermatomes. To the best of our knowledge,
      there is no report of this constellation. Therefore, we suggest that lymphangioma
      circumscriptum may be considered as a skin finding of Cobb syndrome.

PMID- 8864619
TI  - Hereditary painful callosities with associated features.
AB  - 'Hereditary painful callosities' defines an autosomal dominant nummular
      palmoplantar keratoderma characterized by the development of painful keratotic
      lesions over pressure points. Two unrelated patients with hereditary painful
      callosities with other familial acral abnormalities are reported. To our
      knowledge subtotal congenital leukonychia and symmetrical bone duplication of
      great toes have not been previously described in association with this disorder.

PMID- 8864620
TI  - Livedo reticularis and thrombotic purpura related to the use of diphenhydramine
      associated with pyrithyldione.
AB  - We describe the case of a young woman who habitually took large doses of a
      combination of diphenhydramine and pyrithyldione. She complained of arthralgia,
      painful recurring plaques and nodules, together with persistent reticular
      purpuric mottling and areas of necrosis on her legs. There were positive
      antinuclear antibodies and rheumatoid factor and histologically massive
      thrombosis of the dermal vessels without signs of vasculitis. Other cases of
      similar adverse reactions attributed to this drug combination used as a hypnotic
      have been described.

PMID- 8864621
TI  - Acquired eyelash trichomegaly and alopecia areata in a human immunodeficiency
      virus-infected patient.
AB  - We describe a human immunodeficiency virus (HIV) seropositive man with acquired
      eyelash trichomegaly and alopecia areata. This combination of clinical
      manifestations is intriguing since the new onset of elongated eyelashes in
      patients with acquired immunodeficiency syndrome has usually been associated with
      severe immunosuppression and alopecia areata has a presumed autoimmune etiology
      that requires T cell activation. The occurrence of these dichotomous conditions
      illustrates the potential selective pathogenesis of progressive HIV infection.

PMID- 8864622
TI  - Fixed exanthema induced by ultraviolet radiation.
AB  - An unusual cutaneous eruption of the feet and lower limbs induced by ultraviolet
      radiation in a 30-year-old caucasian man is presented. Previous reports in the
      literature and the present case indicate that sunlight and UV radiation may
      provoke fixed eruptions themselves without drug exposure.

PMID- 8864623
TI  - Acute generalized exanthematous pustulosis induced by dexamethasone injection.
AB  - A 52-year-old woman, without a history of psoriasis, developed a widespread,
      sterile pustular eruption on the trunk and extremities 2 days after subcutaneous
      injection of dexamethasone solution. Skin biopsy revealed subcorneal pustules
      filled with neutrophils and moderate lymphohistiocytic infiltrate with a few
      eosinophils in the dermis. There was no evidence of vasculitis. Patch testing
      showed positive pustular reactions to dexamethasone solution. Histology of this
      pustule also resembled that of the original eruption. To our knowledge, acute
      generalized exanthematous pustulosis due to corticosteroid has not been
      previously reported.

PMID- 8864624
TI  - Multiple cutaneous sensitization to nonsteroidal anti-inflammatory drugs.
AB  - The use of topical nonsteroidal anti-inflammatory drugs is widespread
      (particularly in countries bordering the Mediterranean). Compared to their wide
      use, the incidence of published adverse cutaneous effects appears minimal,
      although they are increasing. Most of them are a form of allergic contact
      dermatitis (ACD). Multiple sensitization and/or cross-reactions are rarely
      reported. Interestingly, our patient presented ACD with diclofenac and
      etofenamate (both from different chemical groups) and, furthermore, patch tests
      were positive with bencydamine and indomethacin (both indolacetic acid
      derivatives), piroxicam and fepradinol. We think that our results could not be
      explained due to cross-reactivity, and that multiple sensitization was more
      likely.

PMID- 8864625
TI  - Red pepper-induced dermatitis in breast-fed infants.
AB  - We report a transient, erythematous dermatitis that formed in 2 infants shortly
      after breast-feeding from their mothers who had ingested food flavored with red
      pepper, although the mothers did not display any signs of dermatitis.

PMID- 8864626
TI  - Sporadic hypomelanosis of Ito with focal hypertrichosis in a 16-month-old girl.
AB  - We report the case of a 16-month-old girl with hypomelanosis of Ito, a relatively
      rare phenotype associated with neurocutaneous manifestations. The characteristic
      hypopigmented streaks along the Blaschko lines were associated with
      hypertrichosis of the genitals and shins, as well as musculoskeletal and dental
      anomalies. An underlying endocrinologic disorder of the hypertrichosis could be
      excluded. This presumes focal hypertrichosis as another phenotypic expression of
      mosaicism in this disease.

PMID- 8864627
TI  - Interferon-induced vitiligo in a patient with chronic viral hepatitis C
      infection.
AB  - Vitiligo is an autoimmune disease characterized by depigmentation of the skin due
      to destruction of melanocytes. Interferons have been used for the treatment of
      chronic hepatitis C and some malignancies. We report interferon alpha-2a-induced
      vitiligo in a male patient with chronic active hepatitis C. All skin lesions
      disappeared completely without requiring therapy after discontinuation of
      interferon. This case suggests that vitiligo may be developed during interferon
      therapy as a side effect.

PMID- 8864628
TI  - Lichenoid drug eruption following the Blaschko lines.
AB  - Eruptions similar to those of lichen planus (LP) are associated with systemic
      diseases or have been induced by many drugs. Linear lesions as a Koebner effect
      are frequently found in LP but isolated long, narrow, linear lesions, which may
      extend the whole length of the limb, are rare though rather more common in
      childhood. Some cases of zonal or zosteriform LP have been described in the
      literature. We describe a case of LP with a linear distribution following the
      Blaschko embryologic lines induced by nicergoline in a 65-year-old woman with a 6
      month history of a pruritic eruption of erythematoviolaceous papules on the left
      breast, trunk and upper limb, with histological features of LP It would be the
      first case of linear LP associated with drugs.

PMID- 8864629
TI  - Solitary eccrine syringofibroadenoma (or eccrine syringofibroadenomatous
      hyperplasia?) and diabetic polyneuropathy.
AB  - A 70-year-old diabetic woman with sensory polyneuropathy presented with
      osteonecrosis of the toes and a plaque-like lesion on the dorsum of the
      ipsilateral foot. Histological diagnosis of eccrine syringofibroadenoma (ES) was
      made. A review of the literature reveals several cases of solitary ES of the foot
      in diabetic patients with peripheral neuropathy. This variant of ES seems to be
      an eccrine sweat duct hyperplasia during the restoration of skin structures
      damaged by traumas in a situation of peripheral neuropathy. Diabetes and
      polyneuropathy should be searched for in patients with ES, particularly in acral
      locations.

PMID- 8864630
TI  - Acute generalized exanthematous pustulosis induced by hydroxychloroquine.

PMID- 8864631
TI  - Pemphigus vulgaris in two MHC-haploidentical brothers.

PMID- 8864632
TI  - Adenocarcinoma of the mouth in a patient with psoriasis under short-term
      cyclosporine therapy.

PMID- 8864633
TI  - Postmenopausal female rosacea patients are more disposed to react with migraine.

PMID- 8864634
TI  - Combination of local PUVA-therapy and interferon alpha-2A in the treatment of
      tumoral stage mycosis fungoides.

PMID- 8864635
TI  - Cardiovascular mortality and morbidity in type-2 diabetes mellitus.
AB  - A representative number of prospective studies clearly indicate that
      cardiovascular morbidity and mortality is significantly increased in type-2
      diabetic patients in comparison with non-diabetic control subjects. The
      cardiovascular death rate is 4.4 fold increased in those diabetic patients
      presenting none of the classical risk factors (hypertension, hypercholesterinemia
      or smoking) compared with age-matched control subjects (MRFIT). A decreased
      survival rate after myocardial infarction, congestive heart failure and an
      increased occurrence of silent ischemia are responsible for the poor prognosis of
      type-2 diabetic patients. Recent studies indicate that haemostatic abnormalities
      and endothelial dysfunction are important risk factors for coronary events in
      diabetic as well as in nondiabetic patients. In newly diagnosed type-2 diabetic
      patients a similar prevalence of myocardial infarction and angina compared to
      previously known type-2 diabetes was found. The long prediabetic period and
      clustering of risk factors may be very relevant for the high prevalence of
      cardiovascular disease already at diagnosis of type-2 diabetes. More recent
      studies performed in Scotland and Verona demonstrated a mortality risk
      approximately only 50% higher than in nondiabetic subjects. The reduction in the
      mortality risk could reflect an improvement in diabetes prognosis from the 1960s
      to the 1980s. Recent observations in type-2 diabetic patients from Finland
      indicate that glycemic control is an important predictor for coronary heart
      disease morbidity and mortality. However incidence of coronary heart disease is
      only low in those patients presenting with a HbAlc value below 6.0%. More
      information will be available after analysis of the United Kingdom prospective
      diabetes study. (UKPDS).

PMID- 8864636
TI  - Influence of hypoglycaemic sulphonylureas on the electrophysiological parameters
      of the heart.
AB  - The effects of different ATP-sensitive potassium channel blocker sulphonylurea
      drugs (0.01-1000 mumol/l, or kg) were investigated in vitro on the electrical
      threshold, conduction time, effective refractory period and automaticity of left
      atrium, right ventricle and Purkinje fibers as well as in vivo on strophanthidin
      , ischaemia- and reperfusion-induced arrhythmias and on vagal nerve stimulation
      in rabbits, rats and dogs. They proved to exert different actions not only
      quantitatively but also qualitatively. In vitro, glibenclamide diminished the
      electrical activity of the heart muscle preparations, while chlorpropamide
      stimulated it, whereas glimepiride does not seem to affect it markedly. In vivo,
      glibenclamide and glimepiride decrease, while gliclazide and tolbutamide
      increase, the amount of strophanthidin- and ischaemia-induced ventricular ectopic
      beats and the duration of ventricular fibrillation. In the case of glimepiride
      the effect was dependent on the metabolic state. The different actions of
      sulphonylureas on the electrophysiological properties of the heart cannot be
      explained solely by their ATP-dependent potassium channel blocking potencies.

PMID- 8864637
TI  - Influence of oral antidiabetic treatment on electrocardiac alterations induced by
      myocardial infarction.

PMID- 8864638
TI  - What kind of cardiovascular alterations could be influenced positively by oral
      antidiabetic agents?
AB  - Since the first publication of the University Group Diabetes Programme in 1970
      the possible deleterious cardiovascular effects of certain hypoglycaemic
      sulphonylurea products has been well known. In contrast, international knowledge
      of the advantageous cardiovascular effects of certain sulphonylurea compounds
      became available recently. Glibenclamide decreases the incidence of fatal
      myocardial infarction and the development of ventricular fibrillation in patients
      suffering from acute myocardial infarction. It also lowers the incidence of
      ventricular ectopic beats in digitalized patients compared with patients treated
      with other investigated sulphonylurea compounds. The survival of patients treated
      with glibenclamide, insulin or diet alone is longer after the first attack of
      angina pectoris or after first acute myocardial infarction compared with those on
      other investigated sulphonylurea therapy. Glibenclamide decreases
      arrhythmogenesis during acute myocardial infarction in rats and strophanthin
      cardiotoxicity in rabbits. Arterial blood pressure and myocardial contractile
      force are not influenced by glibenclamide whereas these parameters are increased
      by other investigated sulphonylurea compounds. Consequently, deleterious
      cardiovascular effects of certain hypoglycaemic sulphonylurea drugs may
      contribute to the high cardiovascular mortality rate in diabetes mellitus, partly
      due to the effect on membrane channels and partly due to independent cardiac and
      extracardiac actions. Finally, recent observations suggest that glimepiride has a
      more advantageous cardiovascular effect than glibenclamide.

PMID- 8864639
TI  - Clinical profile of the novel sulphonylurea glimepiride.
AB  - Glimepiride is a new generation sulphonylurea being prudently characterized in
      more than 2000 NIDDM patients. It has a short onset of action and a long duration
      of action. The same pharmacodynamic effect as with traditional sulphonylureas is
      achieved with secretion of less insulin, suggesting a possible extrapancreatic
      action. Glimepiride is given once daily in doses from 1-8 mg/day. 100% absolute
      bioavailability and the absence of a food interaction guarantee highly
      reproducible pharmacokinetics. Glimepiride is a remarkably safe drug especially
      in NIDDM patients at high risk e.g. the renally impaired, elderly or physically
      very active person. Hypoglycemia is less frequent in the first weeks of treatment
      than with glibenclamide. Ongoing studies are investigating the possible
      beneficial clinical effect of its different binding behavior to the potassium
      channel, especially in the heart.

PMID- 8864640
TI  - Haemodynamic and other effects of sulphonylurea drugs on the heart.
AB  - Antidiabetic sulphonylureas have attracted a great deal of interest in
      experimental cardiology to evaluate the role of ATP-sensitive potassium channels
      in the cardiovascular system. It is well established that KATP channels are
      present in cardiac cells and also in vascular smooth muscle cells and are
      implicated in the regulation of myocardial and vascular function. It follows that
      drugs which open, or inhibit the opening of these channels, might profoundly
      modify cardiovascular function both under physiological and pathophysiological
      conditions. This paper reviews the evidence for the role of KATP channels in the
      cardiovascular system and discusses how the different generations of
      sulphonylurea drugs interfere with cardiac function. We will particularly
      concentrate on the haemodynamic effects of different sulphonylureas and shortly
      discuss how these drugs modify ischaemia-reperfusion arrhythmias.

PMID- 8864641
TI  - Cardiovascular effects of sulphonylurea derivatives.
AB  - The classical sulphonylurea derivatives like glibenclamide and tolbutamide are
      widely prescribed in non-insulin dependent diabetes mellitus in order to
      stimulate insulin secretion. The insulinotropic effect of these agents is based
      on the closure of adenosine-5'-triphosphate (ATP)-sensitive potassium channels
      (KATP-channels) in the beta-cells of the pancreas. Interestingly, the
      cardiovascular system also shares these KATP-channels. The open state probability
      of these channels is regulated by the intracellular concentration of ATP. During
      ischaemia, the KATP-channels are thought to open by a fall in the cytosolic ATP
      concentration. The increase in the extracellular adenosine concentration, and the
      release of endothelium-derived hyperpolarizing factor (EDHF) during ischaemia may
      further contribute to the opening of cardiovascular KATP-channels. Sulphonylurea
      derivatives like glibenclamide and tolbutamide have been reported to block the
      opening of KATP-channels in several types of tissues including myocardial and
      vascular smooth muscle cells. Since the opening of KATP-channels is regarded as
      an endogenous cardioprotective mechanism, the blocking effect of sulphonylurea
      derivatives in the cardiovascular system may have deleterious effects. Human
      studies on this issue have just been initiated, and preliminary results point
      towards a significant interaction between glibenclamide and cardiovascular KATP
      channels at clinically relevant concentrations. In this regard, the introduction
      of more pancreas specific sulphonylurea derivatives like glimepiride, which do
      not interact with cardiovascular KATP-channels, is a promising development.

PMID- 8864642
TI  - Long-term influence of glycaemic control on cardiovascular risk in NIDDM.

PMID- 8864643
TI  - Role of elevated lipids in diabetic cardiomyopathy.
AB  - Diabetic cardiac dysfunction appears to be associated with an increase in plasma
      lipids especially triglycerides. Drugs that lower plasma lipids will usually
      improve cardiac performance in diabetic rats. More recently, an association
      between decreased cardiac glucose metabolism resulting from increased utilization
      of fatty acid metabolism in the diabetic myocardium has been suggested. Of the
      drugs tested, those drugs that decreased plasma lipids and improved cardiac
      glucose metabolism also improved cardiac performance. Drugs, such as clofibrate,
      which decreased triglyceride levels and did not enhance cardiac performance in
      diabetic rats will be examined in the near future in order to test the
      hypothesis.

PMID- 8864644
TI  - Cardiac membrane Ca(2+)-transport in alloxan-induced diabetes in rats.
AB  - In order to determine if cardiac membrane Ca(2+)-transport activities are altered
      in chronic diabetes induced by alloxan, rats were given an intravenous injection
      of 65 mg/kg and the hearts were used 8 weeks later. Some 4 weeks, diabetic
      animals were injected with insulin (3 U/day) for 4 weeks. Both sarcolemmal (SL)
      and sarcoplasmic reticulum (SR) membranes were isolated from the ventricular
      tissue and their Ca(2+)-transporting activities were determined. SL Na(+)
      dependent Ca2+ uptake, ATP-dependent Ca2+ uptake and Ca(2+)-stimulated ATPase
      activities were depressed in the diabetic heart. Likewise, SR ATP-dependent Ca2+
      uptake activity in the diabetic heart was markedly decreased in comparison to the
      control preparations. These defects in diabetic SL and SR Ca(2+)-transport
      activities were prevented by treatment of diabetic animals with insulin. The
      results from the alloxan-rat model of diabetes support the view that membrane
      abnormalities with respect to Ca2+ handling may lead to the occurrence of
      intracellular Ca2+ overload and the development of diabetic cardiomyopathy.

PMID- 8864645
TI  - Functional responses of the left and right heart of diabetic rats to alpha- and
      beta-adrenergic receptor stimulation.
AB  - It was the aim of the present study to examine the influence of alpha-and beta
      receptor stimulation on the function of the right (RV) and left (LV) ventricle of
      streptozotocin-diabetic rats (STZ; 60 mg.kg-1; n = 14). Phenylephrine (PE; 3
      mg.kg-1.h-1) or isoproterenol (ISO; 24 micrograms.kg-1.h-1) were infused
      intravenously for 20 min 4 weeks after STZ injection. The hemodynamic parameters
      were measured on intact, anaesthetized animals with special Millar ultraminiature
      tipcatheter manometers. In the non-diabetic animals (n = 15), PE caused a
      significant elevation of left ventricular systolic pressure (LVSP) from 138.5 +/-
      3.2 to 205.4 +/- 7.5 mmHg and raised heart rate (HR) from 362 +/- 12.6 to 399 +/-
      17.2 beats.min-1 (mean +/- S.E.M.; P < 0.05). LVSP and HR were significantly
      lower in the diabetic animals under control conditions (110.5 +/- 6.4 mmHg and
      273 +/- 16.0 beats.min-1, respectively) and not affected by PE. ISO induced a
      significant and comparable decrease in diastolic aortic pressure (DAP) and an
      increase in HR in both the non-diabetic and diabetic group. The PE-induced
      enhancements of LV dP/dtmax and RV dP/dtmax from 10533 +/- 805 to 21533 +/- 1386
      and from 2044 +/- 262 to 3867 +/- 733 mmHg.s-1 were significant in the control
      animals. In the diabetic rats, LV dP/dtmax was lower (5971 +/- 901 mmHg.s-1) and
      was increased by PE to the range of control rats (11171 +/- 1591 mmHg.s-1). The
      PE-induced elevation of RV dP/dtmax from 2028 +/- 284 to 2771 +/- 391 mmHg.s-1
      was less pronounced in the diabetic rats than in the controls. Under the
      influence of ISO, the increase of dP/dtmax in both ventricles was comparable to
      the effect of PE and fully preserved in the diabetic animals. Right ventricular
      systolic pressure (RVSP) was increased under PE and ISO in both groups to
      comparable values. These results demonstrate that the in vivo response to beta
      adrenoceptor stimulation is well preserved in the diabetic rat, while the effects
      of alpha-stimulation are markedly reduced, especially in the left ventricle and
      systemic circulation.

PMID- 8864646
TI  - Intracellular pH control mechanisms in the diabetic myocardium.
AB  - Intracellular pH (pHi) regulation and the consequences of this regulation may
      play a crucial role during ischaemia and especially on reperfusion after an
      ischaemic episode. A significant decrease in Na+/H+ exchange activity was first
      demonstrated in papillary muscles isolated from hearts of diabetic rats, and
      recently confirmed in diabetic rat isolated ventricular myocytes. This depressed
      activity of one of the major pHi regulatory mechanisms may afford some protection
      against ischaemia/reperfusion injury. A protection was indeed observed in
      perfused hearts isolated from diabetic rats, in which there was a markedly
      improved recovery of contractility following ischaemia, comparable to that
      obtained with a pharmacological block of Na+/H+ exchange in normal hearts. This
      was associated with a markedly slower pHi recovery.

PMID- 8864647
TI  - Diabetic cardiomyopathy in rats: biochemical mechanisms of increased tolerance to
      calcium overload.
AB  - Abundant information is now available about changes in subcellular organelles
      that are responsible for the impaired intracellular calcium homeostasis in
      diabetic cardiomyopathy. Some of these changes concern heart sarcolemma and
      include decrease in the following variables: calcium binding, influx of calcium
      through the L-type calcium channels, (Na,K)-ATPase activity and its affinity to
      sodium, Na(+)-Ca2+ exchange, H(+)-Na+ exchange, etc. Diabetic hearts also
      exhibited increased tolerance to calcium, but none of the above membrane
      perturbations were clearly identified as the source of this effect. The present
      study was undertaken in order to identify those alterations appearing in diabetes
      which are specific for the diabetic heart only. Our interest was focused on
      changes in sarcolemmal ATPase activities, particularly those of the (Na,K)-ATPase
      and its activation by increasing concentrations of sodium and potassium. Studies
      were performed in the acute (8 days) and chronic (63 days) phase of development
      of insulin-dependent diabetic cardiomyopathy. Wistar rats were made diabetic by
      administration of streptozotocin. To test the effect of excess calcium, the well
      established model of calcium paradox was used. From the results obtained the
      following conclusions have been made: (a) diabetic hearts exceed normal hearts in
      their tolerance to calcium overload. In this respect the effect of chronic
      diabetes is more pronounced than the effect of acute diabetes; (b) the activities
      of sarcolemmal ATPases in diabetic hearts remain relatively well preserved. For
      this reason and with respect to modulation of calcium tolerance, the changes in
      specific properties of the ATPases, particularly those in the (Na,K)-ATPase,
      outweigh the importance of perturbations in their activities; (c) the enormous
      decrease in affinity of the (Na,K)-ATPase to sodium (increased K(m) value)
      monitored in calcium paradox in acute diabetic hearts was absolutely missing in
      "calcium-tolerant" chronic diabetic hearts. This observation pointed to a
      possible relation that may exist between the specific properties (Na,K)-ATPase
      adapted to work in chronic diabetic hearts and the enhanced calcium tolerance of
      those hearts; (d) the specific mechanism responsible for improved activation of
      the (Na,K)-ATPase by sodium and also partially responsible for potassium ions,
      which is clearly manifested in chronic diabetic hearts upon calcium paradox,
      still remains to be elucidated. Nevertheless, it could be assumed that the same
      mechanism may be also co-responsible for the enhanced tolerance of diabetic
      hearts to calcium.

PMID- 8864648
TI  - Diabetic cardiomyopathy in rats: alleviation of myocardial dysfunction caused by
      Ca2+ overload.
AB  - There is some evidence that diabetic hearts are more resistant to
      ischaemia/reperfusion injury due to alterations in Ca2+ handling. Our objective
      was to explore this hypothesis in the model of Ca2+ overloaded heart (calcium
      paradox, CaP). Diabetes was induced by streptozotocin (45 mg/kg, i.v.). Despite
      regular insulin treatment blood glucose was increased. After a diabetes duration
      of 9 weeks the heart/body weight ratio was higher than in age-matched controls,
      and the heart rate, the coronary flow (CF) and the rate of contraction and
      relaxation was reduced as assessed in Langendorff preparation. Depressed function
      was accompanied by a lower content of high energy phosphates and ultrastructural
      alterations, such as an increased number of glycogen granules, lipid droplets and
      changes in the walls of capillaries leading to the narrowing of their lumen. In
      controls, readmission of Ca2+ into Ca(2+)-depleted hearts resulted in extensive
      deterioration of heart function, development of contraction bands,
      ultrastructural damage and loss of ATP. Diabetic hearts, despite impaired
      performance before CaP, showed an improved recovery of heart function manifested
      by restoration of electrical and contractile activity, as well as CF after Ca2+
      repletion. This corresponded to better maintenance of energy metabolism and
      preservation of ultrastructure. In conclusion, diabetic hearts exhibit greater
      resistance to Ca2+ overload. Depressed heart function may account for this
      protective effect: bradycardia facilitates saving ATP; lower CF results in a
      slower rate of Ca2+ washout from the heart during Ca2+ depletion thus causing
      less damage to the cell membrane and maintenance of its integrity.

PMID- 8864649
TI  - Resistance of diabetic rat hearts to Ca overload-related injury. Histochemical
      and ultrastructural study.
AB  - The enzymatic histochemical and ultrastructural alterations of the rat heart
      during development of streptozotocin (STZ) induced diabetic cardiomyopathy were
      studied. Moreover, the response of the isolated diabetic hearts to Ca overload-Ca
      paradox-was investigated. In the early stage of diabetes (1 week of diabetes), no
      apparent histochemical changes were observed but gentle alterations of the
      ultrastructure of the myocytes and particularly capillaries were found.
      Structural changes of the myocytes and microangiopathy accompanied by decreased
      activities of some enzymes (phosphorylase, various dehydrogenases, ATPase)
      progressed with time and were more pronounced late in diabetes (9 weeks). Ca
      paradox induced severe structural damage of the majority of cardiomyocytes and
      loss of the cellular integrity, and marked decrease in activities of all enzymes.
      However, in acute diabetic heart only partial Ca paradox was observed. It was
      manifested by transmural heterogeneity of structural and enzymatic histochemical
      changes. Evident preservation of the ultrastructure and enzyme activities of the
      myocardium was revealed in late stage (9 weeks) of diabetes. It can be concluded
      that diabetes results in prevention of the Ca overload in rat myocardium in
      vitro. Disturbances in coronary perfusion associated with microangiopathy as well
      as altered Ca handling and depressed heart function may account for delayed
      development of Ca paradox in diabetic heart.

PMID- 8864650
TI  - Mitochondrial DNA mutations in diabetic heart.
AB  - Mutations of mitochondrial DNA have been found in cardiomyopathic and diabetic
      patients as well as mitochondrial myopathic patients. Mitochondrial DNA mutations
      are maternally transmitted. It has also been reported that these mutations can be
      acquired under the influence of free radicals. This article is a mini-review
      about mutations of mitochondrial DNA related to the diabetic heart.

PMID- 8864651
TI  - Microvascular functional abnormalities in diabetes: the role of the endothelium.
AB  - The development of techniques for measuring microvascular pressure, flow and
      permeability in man has allowed the construct of a pathophysiological framework
      for the development of diabetic microangiopathy. In insulin dependent disease the
      abnormalities observed conform to the haemodynamic hypothesis with early
      elevation of capillary pressure playing a primary role. In non insulin dependent
      diabetes differences are apparent, supporting the concept that changes in
      microvascular vasodilatory mechanisms may antedate the emergence of diabetes.
      Given the crucial role played by the endothelium in the regulation of local
      microvascular haemodynamics it is not surprising that disturbance of this tissue
      has been implicated in the pathogenetic process, an assertion supported by
      mounting experimental evidence suggesting that the nitric oxide pathway is
      crucially involved.

PMID- 8864652
TI  - Myocardial alterations in diabetes and hypertension.
AB  - Diabetes mellitus is a complex group of diseases that has hyperglycemia as a
      common metabolic abnormality. Although it is well-known that diabetic patients
      are susceptible to the effects of large vessel atherosclerosis with specific
      cardiac and cerebral complications, the association of diabetes mellitus with
      cardiac dysfunction caused by cardiomyopathy in the absence of significant
      coronary artery disease has been recognized for many years. However, the
      pathogenesis of diabetic cardiomyopathy remains unknown and has been somewhat
      controversial. Specifically, whether diabetes mellitus with its metabolic effects
      is sufficient to account for cardiomyopathy remains to be proven. This paper
      reviews the evidence for and against a metabolic etiology. In addition, we review
      the clinical and experimental evidence that supports the view that diabetes
      mellitus acts together with hypertension to produce structural damage in the
      heart that manifests as ventricular dysfunction and ultimately congestive heart
      failure. The concomitant effects of the metabolic derangements of diabetes and
      the vascular abnormalities associated with hypertension may lead to microvascular
      induced tissue injury. Findings supporting this hypothesis are presented, along
      with observations suggesting that treatment with vasodilating calcium channel
      blockers or angiotensin converting enzyme inhibitors may be beneficial in regard
      to tissue pathology and mortality in experimental models. Recent clinical studies
      also support a role for the microcirculation in diabetics. Finally, it is
      suggested that if the microcirculation is pathogenetically involved in diabetic
      cardiomyopathy, then agents that improve microcirculatory flow along with tight
      control of hypertension may be as beneficial in the treatment or prevention of
      diabetic cardiomyopathy as strict metabolic control of hyperglycemia.

PMID- 8864654
TI  - Restoration of vascular endothelial function in diabetes.
AB  - Nitric oxide (NO) is believed to mediate the phenomenon known as endothelium
      dependent relaxation (EDR). NO synthase produces NO from its precursor, arginine
      (ARG). We have previously demonstrated impaired EDR in diabetic blood vessels. In
      this study, we investigated a possible mechanism for defective EDR in
      experimental diabetes and whether pancreatic islet transplantation could reverse
      established endothelial dysfunction. Streptozotocin-induced diabetic rats were
      maintained for 8 or 12 weeks. NO-mediated EDR was assessed in isolated thoracic
      rings ex vivo. A group of untreated diabetic rats received syngeneic islet
      transplantation at 8 weeks of diabetes and were tested for EDR after 4 weeks of
      euglycemia. EDR to acetylcholine was impaired in untreated diabetic rings.
      Endothelium-independent relaxation to nitroglycerin was unaltered. In vitro
      incubation of diabetic rings with 3 mM L-ARG (but not D-ARG) improved EDR to
      acetylcholine in rings from 8-week but not 12-week diabetic rats. L-ARG did not
      alter EDR in control rings nor relaxation to nitroglycerin in control or diabetic
      rings. Islet transplantation at 8 weeks of diabetes normalized blood glucose,
      plasma arginine and total glycosylated hemoglobin while restoring normal EDR. In
      conclusion, a defect in substrate/supply for NO synthesis is acutely reversed by
      ARG supplementation at early but not at later stages of diabetes. Also,
      preemptive surgical intervention with islet transplantation prior to the ARG
      insensitive phase is an effective strategy to reverse established endothelial
      dysfunction in diabetes mellitus.

PMID- 8864653
TI  - Impairment of endothelium dependent relaxation in the diabetic rat heart:
      mechanisms and implications.
AB  - An increased oxidative stress has been suggested to contribute to disturbances in
      the regulation of coronary flow and the increased cardiac risk in diabetes. Using
      the isolated perfused heart of streptozotocin-diabetic rats we could recently
      show [21] that the basal and the maximal coronary flow (tested by infusion of
      sodium nitroprusside) are not altered in diabetes, but that the 5-HT stimulated
      endothelial dependent increase in coronary flow becomes progressively impaired.
      This defect of the endothelium dependent vasodilatation was prevented by
      perfusion of the hearts with superoxide dismutase and pre-treatment of the
      diabetic rats with tocopherol-acetate. Perfusion of the hearts with indomethacin
      to inhibit the synthesis of vasoconstricting prostaglandin endoperoxides did not
      improve the disturbed 5-HT induced, endothelium dependent increase in coronary
      flow. Furthermore, acute variations of the glucose concentration in the perfusion
      medium did not affect the coronary flow significantly. In myocardium, the
      constitutive endothelial NO synthetase was nearly exclusively expressed with the
      highest activity in endothelium, as determined from experiments using isolated
      cardiac endothelial cells. The activity of NO synthetase determined by conversion
      of arginine to citrulline was significantly increased in diabetes. In line with
      this observation, the concentration of arginine in plasma was reduced, but that
      of citrulline elevated. Additionally, the renal elimination of nitrite was
      enhanced in diabetes. These data suggest that the impaired endothelium dependent
      relaxation observed in the diabetic myocardium is presumably not caused by a
      diminished synthesis and release of NO, but by an accelerated inactivation of NO
      by superoxide anions. We suggest that the increased NO generation reflects a
      compensatory mechanism to balance the enhanced inactivation of NO.

PMID- 8864655
TI  - Cardiovascular syndromes X, endothelial dysfunction and insulin resistance.
AB  - Cardiac Syndrome X (microvascular angina) and the more recently described
      metabolic Syndrome X (an epidemiological association between insulin resistance
      and atheroma, dyslipidaemia, and hypertension) may have more in common than the
      chance of their common sobriquet, in view of evidence that microvascular angina
      too is characterised by insulin resistance and endothelial dysfunction. The
      implications are discussed.

PMID- 8864656
TI  - The VPS8 gene is required for localization and trafficking of the CPY sorting
      receptor in Saccharomyces cerevisiae.
AB  - To better understand the process of protein sorting to the yeast vacuole, the
      VPS8 gene was identified and characterized. VPS8 encodes a membrane-associated
      hydrophilic protein of 135 kDa (Vps8p), which is required for the accurate
      sorting of the vacuolar hydrolase, carboxypeptidase Y (CPY). vps8 mutant cells
      missort and secrete CPY as well as a second soluble vacuolar hydrolase,
      proteinase A. In vps8 mutants, several late-Golgi membrane proteins fail to be
      retained in the Golgi apparatus. The Golgi-localized CPY sorting receptor,
      Vps10p, is mislocalized to and aberrantly proteolyzed in the vacuole. Based on
      our findings, we propose that Vps8p is part of a protein complex that associates
      with Golgi and post-Golgi membranes and functions in the retrieval of Golgi
      membrane proteins from the prevacuolar compartment.

PMID- 8864657
TI  - The Saccharomyces cerevisiae processing alpha 1,2-mannosidase is localized in the
      endoplasmic reticulum, independently of known retrieval motifs.
AB  - The yeast-specific alpha 1,2-mannosidase, Mns1p, converts Man,GlcNAc2 to a single
      isomer of Man8GlcNAc2 during N-linked oligosaccharide processing in Saccharomyces
      cerevisiae. Mns1p is a 68 kDa type II integral membrane glycoprotein with a very
      short amino terminal cytoplasmic tail of only two amino acids and a large carboxy
      terminal catalytic region that is homologous to class 1 alpha 1,2-mannosidases
      from mammalian and other species. We have used immunofluorescence and
      immunoelectron microscopy to demonstrate that Mns1p is localized in the
      endoplasmic reticulum in Saccharomyces cerevisiae. As Mns1p contains none of the
      known endoplasmic reticulum retrieval motifs (HDEL, KK or RR), these results
      suggest that Mns1p is localized in the endoplasmic reticulum by a different
      retentin mechanism.

PMID- 8864658
TI  - Localization of cellubrevin to the Golgi complex in pancreatic acinar cells.
AB  - Cellubrevin is the smallest (14 kDa) isoform of the synaptobrevin (VAMP) protein
      family and is found in a wide variety of tissues. Western blot analysis with a
      polyclonal antibody against the unique N-terminus of cellubrevin identified a
      protein of 14 kDa in rat pancreas. This protein distributed predominantly to the
      particulate fractions from the rat exocrine pancreas and was totally resistant to
      NaHCO3 washes, indicating that it is an integral membrane protein. Subcellular
      fractionation of pancreatic homogenates showed enrichment of this protein in the
      smooth microsomal fraction while negligible amounts were present in the zymogen
      granule membrane or the rough microsomal membrane fractions. As seen in other
      tissues, the 14 kDa immunoreactive form was proteolyzed by tetanus toxin. Light
      and electron microscopic immunocytochemistry localized cellubrevin
      immunoreactivity primarily to small vesicles and condensing vacuoles originating
      from the Golgi region, with significantly lower labeling on zymogen granules.
      Based on the intracellular localization of cellubrevin detected in acinar cells
      by immunocytochemistry and cell fractionation, we suggest that cellubrevin may be
      involved in the maturation of secretory granules.

PMID- 8864659
TI  - Brefeldin A and mannose 6-phosphate regulation of acrosomic related vesicular
      trafficking.
AB  - Acrosomal biogenesis represents a unique system for the molecular analysis of the
      various processes involved in vesicular membrane transport. To assess the basic
      membrane trafficking mechanisms used in spermatids, we have used two fluorescent
      lipid compounds that label: a) the Golgi and Golgi-derived vesicles (C5-DMB-Cer),
      and b) endocytic vesicles (FM4-64). Incubation of mouse testicular germ cells at
      33 degrees C for 1.5 h with C5-DMB-Cer revealed that C5-DMB-Cer labeling is
      localized in the Golgi and acrosome of early-maid round spermatid stages, with no
      labeling of the acrosome in late round spermatid stages. Culturing germ cells
      with FM4-64 for 1.5 h at 33 degrees C, showed that FM4-64 labeling in spermatids
      was localized in endocytic vesicles and Golgi of early-mid round spermatid
      stages, whereas in a small population of late round spermatid stages, FM4-64 was
      also localized in the apex region of the acrosome. Incubation with brefeldin A
      (BFA) (5 micrograms/ml) inhibited the distribution of C5-DMB-Cer and FM4-64 to
      the acrosome, however, it did not affect the localization of acrosin-an acrosome
      specific protein-indicating that there was no apparent acrosome disassembly in
      the presence of BFA. Localization of FM4-64 in late round spermatids in the
      presence of 2.5 mM mannose 6-phosphate was found in endocytic vesicles and the
      Golgi, but not the acrosome. These results show that there are at least two
      sources of vesicular transport to the acrosome derived from the Golgi and plasma
      membrane.

PMID- 8864661
TI  - Gamma-tubulin is permanently associated with basal bodies in ciliates.
AB  - Ciliates are of special interest owing to the multiplicity and diversity of their
      microtubule organizing centers (MTOCs). The subcellular localization of gamma
      tubulin in these protozoa has not been extensively studied. The cloning of a
      gamma-tubulin gene in Euplotes (Liang, A., K. Heckmann, Gene 136, 319-322 (1993)
      led us to examine the localization of this protein. We used three polyclonal
      antibodies, JH46, R58 and R70. They had been raised against peptides common to
      mammalian and Aspergillus gamma-tubulins. These regions had 69%, 95%, and 75%
      identity with the corresponding regions of Euplotes gamma-tubulin. Immunoblotting
      (R70) revealed a polypeptide corresponding to the molecular mass of Euplotes
      gamma-tubulin. In Euplotes octocarinatus, gamma-tubulin was detected by
      immunofluorescence (R70) in the basal bodies, the micronucleus and the
      macronucleus throughout the cell cycle. The presence of gamma-tubulin in basal
      bodies and micronuclei was confirmed with the other two antibodies JH46 and R58.
      The permanent association of gamma-tubulin with basal bodies was also observed in
      Tetrahymena thermophila and Paramecium tetraurelia, two ciliates distantly
      related to Euplotes. These results not only extend to ciliates the finding that
      gamma-tubulin is permanently associated with ciliary basal bodies, but also
      demonstrate that gamma-tubulin is present in unconventional MTOCs.

PMID- 8864660
TI  - Immunofluorescence localization of the 90-kDa heat-shock protein to cytoskeleton.
AB  - The 90-kDa heat-shock protein, hsp90, is an abundant and conserved protein
      located predominantly in the cytoplasm. Previous reports have localized a portion
      of the hsp90 to microtubules and to microfilaments. Here, we show that
      colocalization of hsp90 with microtubules is seen after long-term but not short
      term fixation of rat pulmonary endothelial cells with formaldehyde. Under
      conditions of methanol fixation, a significant portion of both hsp90 and the
      hsp90-associated protein p23 is present on fibrillar structures extending
      throughout the cytoplasm of endothelial cells, however, when cells are treated
      with colcemid under conditions that eliminate microtubules, the fibrils condense
      into bright rope-like bundles located in the immediate perinuclear area and
      extending toward the cell periphery. Identical images are observed with an
      antibody against vimentin and the pattern seen after colcemid treatment is
      classical for intermediate filaments. Preabsorption of the anti-hsp90 antibody
      with purified hsp90 prevents the immunofluorescence but preabsorption with
      purified p23 does not, and the reverse is the case for immunofluorescence
      produced by the anti-p23 antibody. These results suggest that hsp90 is able,
      either directly or indirectly via other proteins, to associate with both
      microtubules and microfilaments.

PMID- 8864663
TI  - Hydrogen peroxide-induced chemotaxis of mouse peritoneal neutrophils.
AB  - Directed locomotion of mouse peritoneal neutrophils under agarose was studied,
      and activity of hydrogen peroxide (H2O2) as a chemoattractant was tested in its
      concentration range of 10(-6) to 10(-3) M. It has been found that H2O2 at low
      concentrations (about 10 microM) induces chemotactic activity. This activity was
      not affected by the presence of serum in the agarose medium. Use of bovine serum
      albumin instead of the heat-inactivated bovine serum in the medium had no effect
      on cell locomotion. The H2O2-induced chemotaxis was significantly reduced by
      catalase. Involvement of [Ca2+]i transients in the H2O2-induced chemotactic
      response was shown. These data indicate that H2O2 itself in small quantities can
      act as a chemoattractant without interacting with a plasma precursor to form a
      chemotactic factor. It has been suggested that H2O2 may form an important link
      similar to the second messenger in communication between the cells.

PMID- 8864662
TI  - The major ciliary membrane proteins in Paramecium primaurelia are all
      glycosylphosphatidylinositol-anchored proteins.
AB  - Using a strategy based upon specific features of membrane proteins linked to the
      plasma membrane by a glycosylphosphatidylinositol (GPI) anchor, we have studied
      in the strain 513 of Paramecium primaurelia the glycosylphosphatidylinositol
      (GPI) proteins both in their membrane-bound and soluble forms. 35S-Labeling
      associated with bacterial phosphatidylinositol-specific phospholipase C treatment
      of purified cilia allowed the identification of soluble GPI proteins (devoid of
      their lipid moiety), released from cilia. By labeling with 88[33P]phosphoric acid
      and [3H]ethanolamine, respectively, we identified membrane-bound GPI proteins,
      when anchored in the cilia membrane via the lipid of their GPI tail. We
      demonstrated that, in addition to the SAg (surface antigen) which is a high
      molecular weight protein implicated in the antigenic variation phenomenon, three
      other ciliary membrane proteins were also GPI-anchored. The membrane-bound and
      soluble forms of these GPI proteins had apparent molecular weights, in unreduced
      conditions, of 30,000 and 40 to 50,000, respectively. We named these surface GPI
      proteins SGPs, SGP1 to SGP3, SGP1 (surface GPI protein 1) and SGP2 (surface GPI
      protein 2) were the most abundantly expressed. Only SGP2 displayed a rapid
      turnover. By phosphatidylinositol-specific phospholipase C treatment of the
      membrane proteins recovered in the detergent phase, following partitioning with
      Triton X-114, we demonstrated that the SAg and SGPs are the major ciliary
      membrane proteins of P.primaurelia.

PMID- 8864664
TI  - Cytochemical and immunocytochemical characterization of kinetochores in the
      holocentric chromosomes of Graphosoma italicum.
AB  - In the present paper we have analyzed the trilaminar kinetochores present in the
      mitotic holocentric chromosomes of the heteropteran Graphosoma italicum by means
      of different cytochemical and immunocytochemical techniques at the
      ultrastructural level. The results obtained after EDTA and osmium tetroxide/p
      phenylenediamine, both cytochemical methods for preferential detection of
      ribonucleoproteins, show that the inner and outer kinetochore layers are
      selectively contrasted. These results agree with those previously reported for
      the kinetochores of monocentric chromosomes. Additionally, using cytochemical
      techniques such as ethanolic phosphotungstic acid staining and silver
      impregnation, which recognize proteins, we report a different response of the
      inner kinetochore layer compared with those obtained in the middle and outer
      layers. Finally, our immunoelectron microscopic results employing monoclonal
      antibodies against DNA indicate the absence of this component from the
      kinetochore plates in holocentric chromosomes. Although the trilaminar appearance
      of kinetochores in holocentric chromosomes is very similar to that of the
      localized kinetochores in mammals, our observations imply the existence of
      significant differences on the macromolecular organization of both types of
      kinetochores.

PMID- 8864665
TI  - The cell nucleus in early bovine and caprine preimplantation embryos: fine
      structural cytochemistry and immunoelectron microscopy.
AB  - Fine structural cytochemistry and immunocytochemistry were used to study nucleic
      acids and nuclear proteins in nuclear bodies (NB) of pronuclear and 2-cell bovine
      and caprine embryos on ultrathin sections of paraformaldehyde fixed and Lowicryl
      K4M or LR White embedded specimens. The most striking feature detected in some of
      these nuclear bodies (NBs) was the presence of non-nucleolar proteins known to be
      involved in pre-mRNA splicing. One category of such intranuclear bodies (showing
      a rather dense finely fibrillar composition and named here dense body-DB)
      contained the Sm-antigen (an antigen common to a major group of nucleoplasmic
      spliceosomal snRNPs). Another, more numerous category of NBs differed
      morphologically from the former one by a much looser composition of
      fibrillogranular elements (loose body-LB). Moreover, it showed the presence of
      the non-snRNP splicing factor SC-35, in addition to the Sm-antigen. Both
      categories of these nuclear bodies were distinguished clearly from the nucleolar
      precursor bodies (NPBs) by an absence of immunolabeling of NPB with antibodies
      against nuclear proteins involved in splicing. Moreover, the former NBs are not
      stained with silver, while NPBs already in pronuclei exhibit strong affinity to
      silver. In addition to the immunolabeling in prominent (approx. 0.2-2.0 microns)
      NBs, regularly occurring high concentration of snRNP was revealed in very small
      (approx. 0.05 micron), morphologically poorly defined areas (named here small
      snRNP-enriched areas-SSA), harboring moreover a set of nuclear proteins similar
      to that of the coiled body. Numerous observations of the presence of these small
      areas in nuclear bodies and in their close vicinity, in nucleoplasm, in proximity
      of the nuclear envelope and also in ooplasm suggested that they are possible
      carriers of certain nuclear proteins moving between nuclear bodies, nucleoplasm
      and cytoplasm. A functional relationship of all these embryonic subnuclear
      elements has not been elucidated so far but their mutual relation is suggested,
      since the NPBs and other nuclear bodies usually occur in a close association.
      Fine structural and immunoelectron microscopic observations further suggest a
      similarity of the nuclear bodies in the early ruminant embryo with specific
      intranuclear bodies ("snurposomes") known from Xenopus laevis oocytes. A new and
      striking feature emerging from these observations is a possible involvement of a
      group of nucleoplasmic proteins in a yet unknown way in the differentiation
      processes concomitant with early embryonic nucleologenesis.

PMID- 8864666
TI  - Nuclear accumulation and homeostasis of the unusual polymer beta-poly (L-malate)
      in plasmodia of Physarum polycephalum.
AB  - The plasmodium of Physarum polycephalum specifically contains an unusual
      polyester, beta-poly(L-malate), which is not found in any of the mononucleate
      forms of its life cycle. Plasmodia growing on D-glucose have been analyzed for
      beta-poly(L-malate) in nuclei, cytosol and culture medium after cell
      fractionation, purification by chromatography on DEAE-cellulose and digestion of
      proteins/nucleic acids. Nuclei contained 400 micrograms polymer per 1 g of
      plasmodia, corresponding to a nuclear concentration of 230 mM L-malyl residues,
      not depending on growth rates, lengths of growth periods, and the growth form as
      micro- or macroplasmodia. The synthetic rate increased during the phase of rapid
      enlargement of the nuclei after mitosis. Beta-Poly(L-malate) was polydisperse in
      molecular mass, these tending to be higher in nuclear than in cytosolic extracts
      and being lowest in the culture medium. Beta-Poly(L-malate) was not degraded when
      contained in plasmodia, in contrast to degradation and the occurrence of low
      molecular mass polymer in the culture medium. During pulse-chase feeding with D
      [14C]glucose (0.8 micrometerCi/mol), beta-[14C]poly(L-malate) appearance followed
      kinetics indicating a release of polymer from nuclei into the culture medium when
      it was in excess of a threshold. Injection experiments with purified beta
      [14C]poly(L-malate) revealed a re-entry from the cytoplasm into the nuclei and
      thus the possibility of commutation between the cytoplasm and the nuclei. The
      observed homeostasis in nuclei supports the assumption that beta-poly(L-malate)
      plays an essential role in growing plasmodia.

PMID- 8864667
TI  - Gastrointestinal manifestations in cystic fibrosis.
AB  - CFTR, or cystic fibrosis transmembrane conductance regulator, the gene product
      that is defective in cystic fibrosis, is present in the apical membrane of the
      epithelial cells from the stomach to the colon. In the foregut, the clinical
      manifestations are not directly related to the primary defect of the CFTR
      chloride channel. The most troublesome complaints and symptoms originate from the
      oesophagus as peptic oesophagitis or oesophageal varices. In the small intestinal
      wall, the clinical expression of CF depends largely on the decreased secretion of
      fluid and chloride ions, the increased permeability of the paracellular space
      between adjacent enterocytes and the sticky mucous cover over the enterocytes. As
      a rule, the brush border enzyme activities are normal and there is some enhanced
      active transport as shown for glucose and alanine. The results of continuous
      enteral feeding of CF patients clearly show that the small intestinal mucosa, in
      the daily situation, is not functioning at maximal capacity. Although CFTR
      expression in the colon is lower, the large intestine may be the site of several
      serious complications such as rectal prolapse, meconium ileus equivalent,
      intussusception, volvulus and silent appendicitis. In recent years colonic
      strictures, after the use of high-dose pancreatic enzymes, are being increasingly
      reported; the condition has recently been called CF fibrosing colonopathy. The CF
      gastrointestinal content itself differs mainly from the normal condition by the
      lower acidity in the foregut and the accretion of mucins and proteins, eventually
      resulting in intestinal obstruction, in the ileum and colon. Better understanding
      of the CF gastrointestinal phenotype may contribute to improvement of the overall
      wellbeing of these patients.

PMID- 8864669
TI  - Diabetes mellitus in cystic fibrosis.
AB  - Diabetes mellitus in cystic fibrosis (CF-DM) is increasingly prevalent with age,
      develops insidiously and is characterized by insulinopenia, normal insulin
      sensitivity, increased insulin clearance rate and concomitant exocrine pancreatic
      insufficiency. Since CF-DM impairs overall CF clinical status, including lung
      function, and may result in late diabetic complications, the condition should be
      screened for by annual oral glucose tolerance tests (OGTTs) from the age of 10
      years, and be treated with insulin from the time of diagnosis of CF-DM.

PMID- 8864670
TI  - Hepatobiliary manifestations of cystic fibrosis.
AB  - Cystic fibrosis is the most common, potentially lethal genetic defect in the
      Caucasian population. During recent years it has been increasingly associated
      with a number of hepatic and biliary abnormalities, of which chronic cholestatic
      liver disease is by far the most relevant. Plugging of intrahepatic bile ducts
      with inspissated secretions is thought to play a major role in the pathogenesis.
      Attempts have been made to provide uniform criteria to identify patients with
      early, possibly reversible, hepatic lesions, as well as to assess severity of
      liver disease. It has been estimated that bout 13% of cystic fibrosis patients
      present serum liver enzyme abnormalities, but prevalence of liver involvement is
      likely to be higher. Due to decreasing mortality from extrahepatic causes in
      cystic fibrosis and to the widespread use of laboratory tests and ultrasound
      examination, patients with minor degree of liver involvement will be increasingly
      represented in future. Oral bile acid therapy is promising, but its long-term
      benefits in terms of survival and prevention of major complications of liver
      cirrhosis remain to be established. Liver transplantation is the only potentially
      curative treatment for patients with advanced stage liver disease and mild
      pulmonary involvement.

PMID- 8864668
TI  - Nutritional aspects in cystic fibrosis.
AB  - The achievement and maintenance of energy balance in cystic fibrosis (CF) is one
      of the central aims of management. Growth retardation in affected children and
      wasting in CF adults remain major clinical problems. We consider the basis for
      the energy deficit, examine the spectrum of nutrient imbalance and review the
      current guidelines for dietary management.

PMID- 8864671
TI  - Exocrine pancreatic function in cystic fibrosis.
AB  - Pancreatic dysfunction in cystic fibrosis (CF) begins in utero and, at birth, in
      most cases, cystic fibrosis is characterized by an elevated level of serum
      immunoreactive trypsin (IRT). If most patients with CF typically present
      insufficient pancreatic exocrine function, 10-15% of CF patients have pancreatic
      sufficiency and this status is genetically determined by one or two 'mild'
      mutations in CF transmembrane conductance regulator (CFTR). However, with age,
      these patients can develop pancreatic insufficiency.

PMID- 8864672
TI  - Smoking and inflammatory bowel disease.

PMID- 8864673
TI  - Intestinal migrating motor complexes and blood flow: what is the link?

PMID- 8864674
TI  - Transdermal nicotine compared with oral prednisolone therapy for active
      ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis is largely a disease of non-smokers. Previous
      controlled trials have shown benefit with transdermal nicotine when given with 5
      aminosalicylic acid in active disease but not when given alone as maintenance
      therapy. OBJECTIVE: To examine nicotine alone compared with prednisolone in
      active disease. PATIENTS AND METHODS: Sixty-one patients with active ulcerative
      colitis were treated with either transdermal nicotine patches or 15 mg
      prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses
      of nicotine were given for the first 9 days; patients tolerated between 15 and 25
      mg daily. Most patients were taking mesalazine at entry which was discontinued at
      day 10; a few were taking topical steroids which were discontinued at the onset.
      Clinical, sigmoidoscopic and histological assessments were made at baseline and 6
      weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and
      the clinician made a global clinical assessment. Side effects and serum nicotine
      and cotinine concentrations were monitored throughout the study. RESULTS: Forty
      three patients completed the 6-week trial; of these, 6 of 19 in the nicotine
      group achieved full sigmoidoscopic remission compared with 14 of 24 with
      prednisolone (P = 0.08). In those who completed the 6-week study, there was
      significant improvement within both the nicotine and prednisolone group for the
      St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P <
      0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P <
      0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences
      between groups tend to favour prednisolone, but none reach statistical
      significance. However, on intention-to-treat analyses there is little clear
      evidence of improvement in either group apart from sigmoidoscopic score in which
      prednisolone was associated with a significantly greater improvement than
      nicotine (P < or = 0.05). The nicotine group had more withdrawals than the
      prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration
      (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently
      reported in the nicotine group (average 1.47 episodes per person) than the
      prednisolone group (average 0.61; P = 0.03), the most common of which were
      nausea, light-headedness and tremor. CONCLUSION: In those who managed to complete
      the 6-week study, nicotine alone appeared to be of only very modest benefit in
      acute colitis and was not as effective as 15 mg of prednisolone daily.

PMID- 8864675
TI  - Haemodynamic changes in the small intestine correlate to migrating motor complex
      in humans.
AB  - OBJECTIVE: To evaluate local intestinal blood flow and its relationship to
      fasting gut motility in humans. DESIGN AND METHODS: Regional laser Doppler
      flowmetry (LDF) was carried out for 8 h in 14 tasted volunteers. LDF measured as
      perfusion units (PU) was performed using two single-fibre microprobes attached to
      a small intestinal manometry tube, which monitored migrating motor complexes
      (MMCs). Luminal pressures of small intestine were registered in analogue and
      digital recordings. RESULTS: During phase 1 of MMC, PU values of 65 (33-95) and
      37 (20-100) in proximal and distal duodenum were measured. During phase 2, PU
      values increased by 17% and 38%, respectively (each P < 0.001). At phase 3 of
      MMC, corresponding PU values increased by 363% and 443% (each P < 0.001) and
      remained at high levels until termination of phase 3. During phase 3 there was
      aboral propagation of LDF activity. Computerized recordings allowed detailed
      analysis of relationships between LDF pattern and luminal pressures. At pressures
      below 48 (42-54) mmHg, individual LDF cycles and contraction cycles were phase
      displaced at 180 degrees, indicating low perfusion during contractions. When
      pressures exceeded 48 (42-54) mmHg, a decrease in PU was registered and the
      cycling pattern of LDF was abolished. Then, as luminal pressure decreased below
      33 (25-41) mmHg, PU increased by 246%. CONCLUSION: Our findings show a
      relationship between fasting motility and blood flow in the human gut, in which
      the blood flow exhibited a pattern similar to phase 1, 2 and 3 of the MMC.

PMID- 8864676
TI  - Correlation between disease activity and arterial blood pressure in Crohn's
      disease.
AB  - OBJECTIVE: The aim of this study is to assess haemodynamics in patients with
      Crohn's disease (CD) receiving total parenteral or enteral nutrition (TPEN).
      METHODS: We compared changes in systemic arterial blood pressure (BP) before and
      after 48 courses of TPEN in 34 patients with CD and 19 courses of TPEN in 10
      patients with other gastrointestinal diseases. We simultaneously measured the
      Crohn's disease activity index (CDAI) and biochemical parameters. RESULTS: BP
      increased significantly during TPEN in CD patients (after: 85.1 +/- 7.4 mmHg vs.
      before: 75.2 +/- 7.9 mmHg, P < 0.001). The increase in BP was negatively
      correlated with changes in the Crohn's disease activity index. BP decreased
      significantly after TPEN in patients with other diseases (P < 0.001), despite an
      improvement in their general condition. There was no significant difference in
      volume status between CD patients and patients with other diseases. CONCLUSION:
      These findings suggest that determination of arterial blood pressure may be
      useful for assessing disease severity in patients with CD and that a fall in
      blood pressure may contribute to disease activity.

PMID- 8864677
TI  - The influence of ageing on oesophageal motility after ingestion of liquids with
      different viscosities.
AB  - OBJECTIVES: To verify the influence of ageing on oesophageal motility elicited by
      the swallowing of liquids with different viscosities. DESIGN: In order to study
      the effect of ageing on oesophageal function, healthy volunteers of three age
      groups were studied by manometric and scintigraphic methods during the swallowing
      of water and a high viscosity liquid. METHODS: Forty healthy volunteers (20 aged
      20 to 30 years, 10 aged 50 to 60 years and 10 aged 70 to 80 years) were submitted
      to oesophageal manometry during 10 swallows of water, 10 swallows of sugar cane
      syrup and 10 "dry' swallows. Basal pressure of the upper oesophageal sphincter
      and the lower oesophageal sphincter, amplitude, duration and velocity of
      contraction and the duration of the lower oesophageal sphincter relaxation were
      measured. Morphology and peristalsis of contractile waves were studied. The same
      volunteers underwent scintigraphic oesophageal transit studies with the same
      boluses. Oesophageal clearance time and patterns of transit were studied.
      RESULTS: Water and sugar cane syrup did not differ as to quantitative contraction
      parameters, but sugar cane syrup led to a higher incidence of synchronous
      contractions. The three age groups had similar amplitude and velocity of
      contractile waves. The youngest group had shorter duration of contractile waves
      10 and 5 cm above the lower oesophageal sphincter. The oldest group had markedly
      more frequent synchronous contractions and failures of contraction after both
      water and sugar cane syrup swallows. This was associated with a high incidence of
      scintigraphic transit abnormalities in this group. CONCLUSION: Abnormal
      oesophageal peristalsis and incomplete oesophageal emptying of both low and high
      viscosity liquids are significantly more frequent in healthy elderly persons than
      in younger persons.

PMID- 8864678
TI  - K-ras point mutations are rare events in premalignant forms of Barrett's
      oesophagus.
AB  - OBJECTIVE: In Barrett's adenocarcinomas, in contrast to squamous oesophageal
      carcinomas, K-ras point mutations are thought to be a frequent event. The
      frequency of K-ras point mutations in premalignant forms of Barrett's oesophagus
      (metaplasia, dysplasia) leading to adenocarcinoma with increased risk is
      currently not known. To establish the frequency of K-ras mutations in
      premalignant forms of Barrett's oesophagus, we investigated oesophageal biopsy
      specimens with Barrett's metaplastic and dysplastic epithelium for point
      mutations in the K-ras gene/codons 12, 13. DESIGN: A total of 412 biopsies from
      patients with Barrett's oesophagus were histologically classified into biopsies
      with metaplasia (n = 252), dysplasia (n = 105) and adenocarcinoma (n = 11), as
      well as biopsies distant from disease (normal, n = 37 and hyperplastic squamous
      epithelium, n = 7). METHODS: DNA from biopsy specimens was amplified by
      polymerase chain reaction (PCR) with a modified primer for generating a
      restriction site in the case of wild type in codon 12. Wild-type or point
      mutations in the K-ras gene/codons 12, 13 were detected by restriction fragment
      length analysis of the PCR products. RESULTS: Point mutations in K-ras/codon 12
      were found in 9 biopsies (n = 1 in metaplasia, n = 4 in dysplasias, n = 4 in
      adenocarcinomas). All the other biopsies showed the wild type of K-ras/codon 12.
      No K-ras/codon 13 mutation (GGCgly-->GACasp) was observed. CONCLUSION: Mutations
      in K-ras/codon 12 were rarely found in premalignant forms of Barrett's
      oesophagus. Whereas the screening for K-ras point mutations in metaplastic sites
      of Barrett's epithelium seems not to be of practical value, the screening for
      mutations in dysplastic lesions might be helpful to estimate the individual risk
      for progression of Barrett's epithelium to adenocarcinoma. A further evaluation
      in larger numbers of patients is needed.

PMID- 8864679
TI  - Granulocyte colony-stimulating factor administration reverses cadmium-associated
      inhibition of hepatocyte regeneration.
AB  - OBJECTIVE: To document whether the administration of granulocyte colony
      stimulating factor (G-CSF) enhances the impaired regenerative response of
      hepatocytes to partial hepatectomy (PH), in cadmium-pretreated partially
      hepatectomized rats. MATERIALS AND METHODS: Rats were injected intraperioneally
      with 2.5 mg CdCl2/kg body weight, 24h before PH. G-CSF (1500 or 150 micrograms/kg
      body weight) or saline was administered intraperitoneally in cadmium-pretreated
      partially hepatectomized rats at the same time as PH. The liver regenerative
      process was estimated 24h after PH. [3H] thymidine incorporation into liver DNA,
      liver thymidine kinase (TK) activity, mitotic index and proliferating cell
      nuclear antigen (PCNA) immunostaining were used as indices of hepatocyte
      proliferation. RESULTS: G-CSF administration in cadmium-pretreated partially
      hepatectomized rats restored the suppressed DNA biosynthesis and TK activity (P <
      0.001), to levels similar to those found in rats that were partially
      hepatectomized only. The mitotic index and the percentage of PCNA positive nuclei
      in hepatocytes were also enhanced in G-CSF administered cadmium-pretreated
      partially hepatectomized groups of rats. CONCLUSION: The administration of G-CSF
      triggers events that restore the impaired liver regeneration in this model of
      reduced hepatocyte proliferation.

PMID- 8864680
TI  - Effect of omeprazole on Helicobacter pylori urease activity in vivo.
AB  - BACKGROUND: Detection of Helicobacter pylori infection in clinical routine is
      based either on the direct visualization of the bacterium in gastric biopsies by
      histology or microbiology or on the demonstration of urease activity in gastric
      biopsies and by the labelled-urea breath test (UBT). Omeprazole has a strong
      inhibitory effect on H. pylori urease activity in vitro, but its effect in vivo
      and thus its influence on urease-based diagnostic procedures has not been
      investigated systematically. AIM: To investigate whether omeprazole is able to
      inhibit H. pylori urease activity in vivo and, if so, at which doses. PATIENTS:
      Eighteen patients with H. pylori associated chronic gastritis were studied.
      METHODS: H pylori diagnosis was based on histology, rapid urease test and culture
      from antral biopsies. Following a positive H. pylori diagnosis patients received
      omeprazole 20mg (n = 6), 40mg (n = 6) and 80mg (n = 6) once daily for 5 days and
      13C-UBT was performed on day 1, 3 and 5, 30min after each omeprazole
      administration. The 13C-UBT was performed with 200ml 0.1 N citric acid as test
      drink and 75mg 13C-urea. Breath samples were collected before and 30 min after
      13C-urea administration. RESULTS: A significant inhibition of urease activity was
      observed only under high dose omeprazole administration (80 mg/day), and the 13C
      UBT turned negative in three (50%) of these patients after 5 days therapy.
      CONCLUSION: Short-term omeprazole administration reduces H. pylori urease
      activity only at doses as high as 80 mg/day. A direct inhibition of enzyme
      activity as well as a reduction in the number of viable H. pylori bacteria may be
      responsible for this omeprazole-mediated reduction in urease activity. Urease
      based diagnostic procedures for H. pylori are not suitable for patients under
      omeprazole therapy depending on the dose and duration of therapy.

PMID- 8864681
TI  - Dyspepsia as initial symptom of splanchnic vascular insufficiency.
AB  - A patient is reported with an unusual presentation of splanchnic ischaemia,
      causing gastritis. Although mesenteric ischaemia is well described in the
      literature, there is little information on gastric ischaemia resulting in
      gastritis. There was a considerable delay in diagnosis and treatment, adding to a
      complicated course of events. After revascularization the patient made a complete
      recovery.

PMID- 8864682
TI  - Association of self-limited cytomegalovirus colitis and shigellosis in an
      immunocompetent patient.
AB  - Cytomegalovirus (CMV) infection of the colon has been rarely reported in
      immunocompetent patients. Patients with severe acute illness or disseminated CMV
      infection have high mortality. In contrast, the patients with local injury of the
      colon due either to other gastrointestinal infections or to anal intercourse, who
      are otherwise healthy, usually have self-limited disease. The CMV infection is
      believed to be the bystander and may be treated conservatively. Concomitant CMV
      colitis and other gastrointestinal infections occur exclusively in
      immunosuppressed patients. We report, to our knowledge, the first case of co
      infection of the colon with CMV and Shigella in an immunocompetent patient. The
      hypothesis is that the mucosal damage caused by Shigella infection may predispose
      the colon to secondary CMV invasion.

PMID- 8864683
TI  - Streptococcus bovis spontaneous bacterial peritonitis in patients with alcoholic
      cirrhosis.
AB  - Spontaneous bacterial peritonitis (SBP) is a frequent cause of decompensated
      alcoholic cirrhosis. The authors describe the first two cases caused by infection
      with Streptococcus bovis. They suggest that this microorganism may be present in
      the intestinal flora of these patients more frequently than assumed. Furthermore,
      the course of SBP due to S. bovis may be particularly severe.

PMID- 8864684
TI  - Lichen planus and chronic hepatitis C: exacerbation of the lichen under
      interferon-alpha-2a therapy.
AB  - A 51-year-old man was treated for histologically proven chronic hepatitis C with
      3 MU of recombinant interferon-alpha-2a three times a week. Before interferon
      therapy, a mild lichen planus (hypertrophic variant) had been diagnosed, which
      exacerbated within 6 weeks of treatment to a severe erosive oral form. Then
      interferon therapy was stopped because local measures did not improve oral
      lesions. However, the patient tolerated interferon therapy well, and the
      initially four-fold elevated aminotransferase levels returned to normal. Nine
      weeks after discontinuation of interferon therapy, nearly all the buccal mucous
      membrane lesions had disappeared. But 8 weeks after withdrawal of interferon,
      aminotransferase levels rose again to six times the normal range. Treating
      physicians should know that a pre-existing lichen planus would potentially
      exacerbate, as a side effect of interferon-alpha-2a therapy of chronic hepatitis.
      However, further observations are needed to decide its clinical relevance.

PMID- 8864685
TI  - Duodenal ulcer disease.
AB  - An overview is given of the pathogenic mechanisms involved in Helicobacter pylori
      associated duodenal and gastric ulceration. Special attention is given to the
      role of microbial virulence factors, the effects on gastric acid secretion and
      the development of 'gastric type' metaplasia in the duodenal bulb. Cure of the
      infection essentially eliminates ulcer recurrence. Cure also prevents ulcer
      related bleeding. Antibiotic regimens providing a reliable high cure rate are
      briefly discussed. Finally the questions about ulcer disease which remain
      unanswered are summarized.

PMID- 8864686
TI  - Prazosin inhibits MK-801-induced hyperlocomotion and dopamine release in the
      nucleus accumbens.
AB  - This study examined the putative inhibitory effect of the alpha 1-adrenoceptor
      antagonist prazosin (1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2
      furanylcarbonyl)pip erazine) on changes evoked by the psychotomimetic, non
      competitive NMDA receptor antagonist, MK-801((+)-5-methyl-10,11-dihydroxy-5H
      dibenzo-(a,d)cyclohepten-5, 10-imine), in locomotor activity and extracellular
      concentrations of dopamine and its metabolites, dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5
      hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens as assessed by
      microdialysis in freely moving rats. MK-801 (0.1 and 0.3 mg/kg, s.c.) induced a
      significant, dose-dependent increase in horizontal locomotor activity but did not
      affect rearing. Prazosin administration alone (1 mg/kg, s.c.) only slightly
      reduced horizontal activity during an initial 10 min measurement period, although
      it consistently reduced rearing. However, pretreatment with prazosin effectively
      suppressed the locomotor stimulation caused by either dose of MK-801 throughout
      the whole observation period, i.e. 40 min. Both doses of MK-801 significantly
      increased extracellular levels of dopamine in the nucleus accumbens up to
      approximately 90%. In addition, MK-801 dose dependently increased dopamine
      metabolite concentrations in the nucleus accumbens, but 5-HIAA was significantly
      increased only by the high dose of MK-801. When given alone, prazosin did not
      affect either dopamine, DOPAC, HVA or 5-HIAA levels. However, prazosin
      pretreatment effectively blocked MK-801-evoked increases in dialysate dopamine
      concentrations. Consequently, the potent and selective alpha 1-adrenoceptor
      antagonist prazosin was found to specifically suppress MK-801-evoked, but not
      basal dopamine release in the nucleus accumbens, while effectively blocking MK
      801-evoked locomotor stimulation with only negligible effects on basal locomotor
      activity. Thus, alpha 1-adrenoceptor antagonism may act by reducing the
      sensitivity of the mesolimbic dopamine system to pharmacological or environmental
      challenge. Since most antipsychotic drugs exhibit both dopamine D2 receptor and
      alpha 1-adrenoceptor antagonistic properties, they may alleviate psychosis not
      only through blockade of postsynaptic dopamine receptors, but also
      presynaptically on the mesolimbic dopamine system, through their alpha 1
      adrenoceptor antagonistic action. This latter action may contribute to reduce
      evoked dopamine hyperactivity, e.g. in response to stress.

PMID- 8864687
TI  - Dopamine D1 receptor desensitization profile in MPTP-lesioned primates.
AB  - The motor effects of dopamine D1 receptor activation and the optimal way to
      stimulate these receptors were studied in a primate model of parkinsonism induced
      by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), using 2
      selective full dopamine D1 receptor agonists: A-77636 ([1 R,3S] 3-(1'-adamantyl)
      1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1 H-2-benzopyran hydrochloride), and SKF
      82958 (6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3
      benzazepine hydrobromide). A-77636 was administered to one group of primed
      monkeys (N = 4) previously treated with levodopa and other dopamine receptor
      agonists, while SKF 82958 was given to another group of drug-naive monkeys (N =
      3). These drugs have different durations of efficacy, lasting > 20 h and
      approximately 1 h, respectively, and were administered once daily (A-77636) or
      thrice daily (SKF 82958) for 7 days. Both drugs demonstrated excellent
      antiparkinsonian efficacy and locomotor stimulation. However, a rapid,
      functionally important, homologous (selective for D1 receptor agonists)
      desensitization process took place as early as on the second day with the longer
      acting drug and a dose escalation of A-77636 failed to restore the initial
      benefit. Thrice daily dosing at a 4-h interval with the short-acting agent SKF
      82958 maintained the maximal antiparkinsonian response but some shortening in the
      duration of response was observed after several days. These behavioral results
      show that dopamine D1 receptors are susceptible to desensitization after
      prolonged occupancy and can be desensitized profoundly and independently of
      dopamine D2 receptors in vivo in this model. Potent dopamine D1 receptor agonists
      with an intermediate half-life may prove to be better adjuncts in the treatment
      of Parkinson's disease. Clinical entities with pathologically enhanced dopamine
      D1 receptor-linked neural transmission might eventually also benefit from such
      desensitization.

PMID- 8864688
TI  - Dopamine receptor antagonists attenuate conditioned place preference following
      sexual behavior in female Syrian hamsters.
AB  - We assessed the effects of the dopamine D2 receptor antagonists, sulpiride and
      raclopride, on conditioned place preference produced by sexual behavior in female
      Syrian hamsters. Female hamsters treated with sulpiride or raclopride showed high
      levels of sexual behavior (lordosis) that were equivalent to control females
      receiving vehicle injections. The degree of place preference conditioning for
      sulpiride-treated females was marginally reduced, whereas females treated with
      raclopride showed no evidence of conditioning. These results indicate that
      conditioned place preference is a useful means for probing the appetitive
      components of female sexual behavior, and that dopamine D2 receptors are involved
      in this appetitive process.

PMID- 8864689
TI  - 5-HT2A receptor antagonists inhibit potassium-stimulated gamma-aminobutyric acid
      release in rat frontal cortex.
AB  - Several drugs selective for the serotonin 5-HT2A receptor were tested for their
      effects on spontaneous and K(+)-evoked [3H] gamma-aminobutyric acid (GABA)
      release from slices of rat frontal cortex. Under K+ stimulation, the antagonists
      ketanserin, spiperone, R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4
      fluorophenethyl)]- 4-piperidinemethanol (MDL 100,907) and ritanserin inhibited
      GABA release by 12-31%. Rats were treated with the serotonin-depleting agent para
      chlorophenylalanine and with the serotonergic neurotoxin para-chloroamphetamine.
      In para-chlorophenylalanine-treated animals, stimulated GABA release in the
      presence of ketanserin remained depressed. In animals treated with both para
      chlorophenylalanine and para-chloroamphetamine, ketanserin or the hallucinogenic
      agonist (2,5-dimethoxy-4-iodophenyl)-2-aminoethane (2C-I) each appeared to
      decrease stimulated GABA release but this was not significant. However, when
      ketanserin and 2C-I were both present in the superfusion buffer an additive
      inhibitory effect was observed, and GABA release was decreased 30%. These results
      suggest that serotonin facilitates GABA release in cortex via 5-HT2A receptors
      and that the functional response of this system is resistant to serotonin
      depletion.

PMID- 8864690
TI  - Prophylactic effect of serotonin uptake inhibitors against motion sickness in
      Suncus murinus.
AB  - The prophylactic effect of serotonin uptake inhibitors, imipramine and
      fluoxetine, against motion sickness was investigated in Suncus murinus.
      Imipramine (s.c.) and fluoxetine (i.p.) inhibited motion-induced emesis dose
      dependently with ID50 values of 1.7 and 26 mg/kg, respectively. The results
      suggest that increasing the concentration of serotonin in the synaptic cleft can
      prevent motion-induced emesis and that serotonin uptake inhibitors are effective
      as anti-motion sickness drugs.

PMID- 8864691
TI  - Pretreatment with pertussis toxin spinally, but not supraspinally, blocks the
      cold water swimming-induced antinociception in the mouse.
AB  - Mice exposed to cold water swimming (4 degrees C) for 3 min produced a marked
      antinociception. Experiments were designed to determine whether pretreatment with
      pertussis toxin given intrathecally (i.t.) or intracerebroventricularly (i.c.v.)
      attenuates cold water swimming-induced antinociception in male ICR mice.
      Antinociception was measured by the tail-flick test 7 min after cold water
      swimming. I.t. pretreatment with pertussis toxin at a dose of 0.5 microgram for
      24-96 h caused a time-dependent attenuation of cold water swimming-induced
      antinociception. Moreover, i.t. pretreatment with pertussis toxin at doses from
      0.125 to 0.5 microgram for 96 h attenuated cold water swimming-induced
      antinociception in a dose-dependent manner. However, i.c.v. pretreatment with
      pertussis toxin at doses from 0.125 to 0.5 microgram for 24-96 h did not affect
      the cold water swimming-induced antinociception. The present results suggest that
      pertussis toxin-sensitive Gi/G(o) proteins in spinal cord, but not at the
      supraspinal sites, are involved in cold water swimming-induced antinociception.

PMID- 8864692
TI  - Nitric oxide-dependent and -independent modulation of sympathetic
      vasoconstriction in the human saphenous vein.
AB  - The possible modulation by the endothelium of the contractile responses to
      sympathetic nerve stimulation was examined in isolated superfused human saphenous
      vein. Contractile response curves for transmural nerve stimulation and
      noradrenaline were higher in endothelium-denuded than in intact human saphenous
      vein rings. In vessels with endothelium, transmural nerve stimulation- and
      noradrenaline-induced contractions were unaffected by the cyclooxygenase
      inhibitor, indomethacin (10 microM), but were potentiated by the nitric oxide
      (NO) synthase inhibitor, L-N omega-nitro-L-arginine (L-NNA, 3 microM) even when
      combined with D-arginine (0.3 mM), but not with L-arginine (0.3 mM). As in the
      case of noradrenaline, contractile responses to 5-HT, but not to KCI, were
      enhanced by endothelium removal, L-NNA or L-NNA plus D-arginine, but were
      unaffected by L-NNA plus L-arginine. The guanylyl cyclase inhibitor, methylene
      blue (10 microM), potentiated both transmural nerve stimulation- and
      noradrenaline-induced contractions in endothelium intact rings, whereas it
      enhanced, although to a lesser degree, only the neurally evoked contractions in
      endothelium-denuded human saphenous vein. In the vessels without endothelium L
      NNA failed to affect the vasoconstriction induced by both transmural nerve
      stimulation and noradrenaline. Our results suggest that at least two inhibitory
      factors are involved in modulating the sympathetic vasoconstriction in the human
      saphenous vein: (1) at a postjunctional level, NO, the release of which from
      endothelial cells is probably stimulated by the activation of specific receptors,
      and (2) at a prejunctional level, an unidentified vasodilator agent, which is
      unmasked by the removal of the endothelium layer and which is probably co
      released along with noradrenaline, and which acts through the guanylyl cyclase
      pathway.

PMID- 8864693
TI  - Inhibition by bertosamil of cardiac responses to pinacidil or Bay k 8644 in
      isolated dog atria and ventricles.
AB  - We investigated the effects of a novel bradycardiac agent, bertosamil (3-isobutyl
      7-isopropyl-9,9-pentamethylene-3,7-diazabicyclo[3.3.1] nonane
      sesquihydrogenfumarate), on the sinus rate and atrial contractile force and the
      left ventricular contractile force in isolated, blood-perfused dog hearts and the
      blocking effects of bertosamil on the chronotropic and inotropic responses to
      pinacidil and Bay k 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2
      trifluoromethylphenyl)- piridine-5-carboxylate). Bertosamil (0.1-100 nmol) caused
      transient positive, followed by continuous negative, chronotropic responses and
      positive inotropic responses in atria, and increased the left ventricular
      contractile force. Neither propranolol nor atropine affected the cardiac
      responses to bertosamil. Bertosamil (3-100 nmol) dose dependently attenuated the
      negative chronotropic and inotropic responses to pinacidil but not to
      acetylcholine. Bertosamil at a high dose attenuated the positive cardiac
      responses to Bay k 8644, norepinephrine and isoproterenol. These results suggest
      that bertosamil inhibits negative cardiac responses mediated by an ATP-sensitive
      K+ channel but not an acetylcholine muscarinic receptor and, at a high dose,
      attenuates the L-type Ca2+ channel-mediated positive cardiac responses in
      isolated dog hearts.

PMID- 8864694
TI  - The selective endothelin ETA receptor antagonist FR139317 inhibits neointimal
      thickening in the rat.
AB  - Endothelin is known as a potent mitogenic mediator. We tested the in vivo ability
      of FR139,317((R)2-[(R)-2-[(S)-2-[[1-(hexahydro- 1H-azepinyl)]carbonyl]amino-4
      methylpentanoyl] amino-3-[3-(1-methyl-1 H-indoyl)]propionyl]amino-3-(2
      pyridyl)propionic acid), a selective antagonist of the endothelin ETA receptor
      subtype, to inhibit neointimal thickening following photochemically induced
      injury of the endothelium of rat femoral artery. FR139,317 (32 mg/kg s.c., twice
      a day) was administered for 3 weeks after the injury. FR139,317 significantly
      decreased the neointimal area (76.3%) without changing the medial area.
      Therefore, it is suggested that endothelin may play an important role, via mainly
      endothelin ETA receptors, in neointima formation in injured artery.

PMID- 8864695
TI  - Modulation of vascular KATP channels in hypothyroidism.
AB  - The role of vascular KATP channels in hypothyroidism-induced decrease in myogenic
      activity of rat portal vein was examined by using pharmacologically relevant
      concentrations of K+ channel ligands. As compared to controls, a significant
      decrease in the myogenic tone and noradrenaline (10(-9)-10(-5) M)-induced
      contractions was observed in portal veins from hypothyroid rats. In both
      euthyroid and hypothyroid states, pinacidil (10(-9)-10(-5) M) and cromakalim (10(
      9)-10(-5) M) caused concentration-related inhibition of the myogenic tone
      (frequency and amplitude). However, hypothyroidism caused a leftward shift in the
      concentration-response curves of the K+ channel openers with a corresponding
      decrease in their IC50 values both in the absence and presence of the KATP
      channel blocker, glibenclamide (10(-7) M). Further, concentration-dependent
      increase in the frequency of myogenic tone by glibenclamide (10(-8)-3 x 10(-6) M)
      was greater in tissues from hypothyroid rats (EC50 = 2.07 x 10(-7) M; 95% CL,
      1.06-4.05 x 10(-7) M) in comparison to controls (EC50 = 8.07 x 10(-7) M; 95% CL,
      0.53-1.22 x 10(-6) M). These results suggest that a decrease in the myogenic tone
      of rat portal vein may possibly be related to an enhanced opening of the KATP
      channels in hypothyroidism.

PMID- 8864696
TI  - Novel potent selective phenylglycine antagonists of metabotropic glutamate
      receptors.
AB  - The metabotropic glutamate (mGlu) receptor antagonist properties of novel
      phenylglycine analogues were investigated in adult rat cortical slices (mGlu
      receptors negatively coupled to adenylyl cyclase), neonatal rat cortical slices
      and in cultured rat cerebellar granule cells (mGlu receptors coupled to
      phosphoinositide hydrolysis). (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG),
      (RS)-alpha-methyl-4-sulphonophenylglycine (MSPG), (RS)-alpha-methyl-4
      tetrazolylphenylglycine (MTPG), (RS)-alpha-methyl-3-carboxymethyl-4
      hydroxyphenylglycine (M3CM4HPG) and (RS)-alpha-methyl-4-hydroxy-3
      phosphonomethylphenylglycine (M4H3PMPG) were demonstrated to have potent and
      selective effects against 10 microM L-2-amino-4-phosphonobutyrate (L-AP4)- and
      0.3 microM (2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine (L-CCG-1)-mediated
      inhibition of forskolin-stimulated cAMP accumulation in the adult rat cortex. In
      contrast, these compounds demonstrated either weak or no antagonism at mGlu
      receptors coupled to phosphoinositide hydrolysis in either neonatal rat cortex or
      in cultured cerebellar granule cells. These compounds thus appear to be useful
      discriminatory pharmacological tools for mGlu receptors and form the basis for
      the further development of novel antagonists.

PMID- 8864697
TI  - Agonists of cyclic AMP-coupled metabotropic glutamate receptors in adult rat
      cortical slices.
AB  - A number of potential Group 2 and Group 3 metabotropic glutamate receptor (mGlu
      receptor) agonists were investigated in adult rat brain cerebrocortical slices.
      The rank order of their potency in inhibiting forskolin-stimulated adenylyl
      cyclase was found to be: (S)-2-amino-2-methyl-4-phosphonobutyric acid (MAP4) >
      (2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine (L-CCG-I) > (1S,3S)-1
      aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD) > (1S,3R)-1
      aminocyclopentane-1, 3-dicarboxylic acid (1S,3R)-ACPD) > (2S,1'R,2'R,3'R)-2-(2,3
      dicarboxycyclopropyl)glycine (DCG-IV) > (S) -2-methylglutamate ((S)-MG) > L
      glutamate > (2S,1'S, 2'S)-2-(2-carboxycyclopropyl)alanine (MCCG) > L-2-amino-4
      phosphonobutyric acid (L-AP4) > L-serine-O-phosphate (SOP). The finding that (S)
      2-amino-2-methyl-4-phosphonobutyric acid was the most potent agonist at these
      metabotropic glutamate receptors is in contrast to its observed potent mGlu
      receptor antagonist action in the neonatal rat spinal cord.

PMID- 8864698
TI  - Cytoskeletal inhibitors impair Ca2+ elevations via neuropeptide Y and other Gi
      coupled receptors.
AB  - Neuropeptide Y, alpha 2-adrenoceptors, thrombin and certain muscarinic
      acetylcholine receptors can couple to elevations of intracellular free Ca2+
      concentrations via Gi-proteins. We have studied the effects of inhibitors of
      microtubules (colchicine, nocodazole, vinblastine) and microfilaments
      (cytochalasin B, cytochalasin D) on these effects in human erythroleukemia (HEL)
      cells. Both types of inhibitors reduced neuropeptide Y-, adrenaline- (via alpha
      2A-adrenoceptors) and thrombin-stimulated Ca2+ elevations while the inactive
      analog beta-lumicolchicine was without inhibitory effects. Similarly, in SK-N-MC
      cells vinblastine inhibited neuropeptide Y and carbachol (via muscarinic
      receptors) stimulated Ca2+ elevations. In HEL cells the inhibitory effects of the
      microfilament inhibitor cytochalasin D and the microtubule inhibitor colchicine
      were not additive. Colchicine, nocodazole or cytochalasin D did not affect the
      binding of the agonist neuropeptide Y. On the other hand, neuropeptide Y and
      thrombin significantly stimulated GTP gamma S binding in the absence but not in
      the presence of colchicine, vinblastine or cytochalasin B. This was not due to
      sequestration of G-protein alpha-subunits, since nocodazole did not affect the
      distribution of immunodetectable Gi alpha 1/2 or Gi alpha 3 between membrane and
      cytosolic fractions. We conclude that disruption of microfilaments or
      microtubules impairs Ca2+ elevations by neuropeptide Y and other Gi-coupled
      receptors by inhibiting receptor/Gi-protein interaction; this does not involve
      impairment of agonist binding to the receptor or redistribution of Gi-protein
      alpha-subunits.

PMID- 8864699
TI  - Oligodeoxynucleotides directed to early growth response gene-1 mRNA inhibit DNA
      synthesis in the smooth muscle cell.
AB  - Vascular smooth muscle cell proliferation plays a central role in the
      pathophysiology of cardiovascular diseases. The induction of the early growth
      response gene-1 (egr-1) mRNA is associated with different cellular processes such
      as cell proliferation. Antisense oligodeoxynucleotides seem to provide a
      promising new pharmaceutical tool for effective modification of the expression of
      specific genes. Hence, in the present study, the effect of 15-mer antisense
      oligodeoxynucleotides (targeted to the initial codon region of the egr-1 mRNA) on
      the angiotensin II- and platelet-derived growth factor-BB-induced growth
      promoting effects of aortic smooth muscle cells was evaluated. Angiotensin II-
      and platelet-derived growth factor-BB induced egr-1 mRNA (3.4 kb) and Egr-1
      protein (80 kDa) in a time- and concentration-dependent fashion. No effects of
      the sense and antisense oligodeoxynucleotides on the agonist-induced elevation of
      the egr-1 mRNA and on the Egr-1 protein could be demonstrated. However, they
      effectively inhibited the angiotensin II- and the platelet-derived growth factor
      BB-induced DNA synthesis. Our findings provide evidence that the
      oligodeoxynucleotides inhibit vascular smooth muscle cell growth via nonantisense
      mechanism(s).

PMID- 8864700
TI  - Cocaine inhibits the release of MPP+ but not dopamine through the rat dopamine
      transporter.
AB  - Transporter-mediated release of dopamine and the parkinsonism-inducing neurotoxin
      1-methyl-4-phenylpyridinium (MPP+) was examined in COS cells, a cell line derived
      from monkey kidney, expressing the rat dopamine transporter. The release of
      preloaded [3H]MPP+ but not [3H]dopamine was dose-dependently inhibited by cocaine
      and other compounds known as dopamine uptake inhibitor, 1-[2
      (diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine (GBR12,935) and
      nomifensine, although the uptake of both [3H]dopamine and [3H]MPP+ was sensitive
      to these compounds. The different sensitivity of the outward transport of
      dopamine and MPP+ to the uptake inhibitors might provide a clue to the identity
      of the specific site(s) for cocaine on the transporter.

PMID- 8864701
TI  - The affinity of adenosine for the high- and low-affinity states of the human
      adenosine A1 receptor.
AB  - The affinity of adenosine for the human adenosine A1 receptor expressed on
      Chinese hamster ovary cell membranes has been measured in the presence and
      absence of GTP. The competitive effect of endogenous adenosine on the binding
      properties of adenosine A1 receptors was estimated from differences in the
      binding of N6-cyclohexyladenosine measured in the absence and presence of
      adenosine deaminase. From these data, the affinity of adenosine for the high- and
      low-affinity states of the human adenosine A1 receptor (7 x 10(7) and 1.3 x 10(5)
      M-1, respectively) was calculated.

PMID- 8864702
TI  - The role of dipyridamole in stroke prevention.

PMID- 8864703
TI  - Ticlopidine or clopidogrel as alternatives to aspirin in prevention of ischemic
      stroke.

PMID- 8864704
TI  - Critique of two putative therapies in stroke prevention using platelet
      inhibitors.

PMID- 8864705
TI  - Respiratory chain encephalomyopathies: a diagnostic classification.
AB  - Mitochondrial encephalomyopathies are a heterogenous group of disorders with
      various biochemical defects of the respiratory chain (RC). Due to the
      considerable phenotypic diversity of the RC encephalomyopathies, they are
      included in the differential diagnosis of many cases of multisystem disease.
      Aside from clinical evaluation and family history, diagnosis can be supported by
      many other sources. The complexity of diagnostic information can make it
      difficult for the clinician to establish the level of certainty at which a RC
      cytopathy is diagnosed in atypical cases. We review the parameters (clinical,
      pathological, biochemical and molecular) which are used to aid diagnosis of RC
      encephalomyopathy and identify levels of abnormality in each that strongly or
      less strongly support the diagnosis. A system is developed that allows
      classification of the diagnosis in possible, probable and definite categories of
      certainty, which will be of value to the clinician.

PMID- 8864706
TI  - Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI
      scans with hemispheric infarcts.
AB  - Cerebral atrophy (CA) in stroke patients is associated with poststroke dementia
      and may reflect underlying neurodegenerative pathology. Therefore, regional CA
      may be valuable to study in patients who develop poststroke dementia. The aim of
      this study was to test the reproducibility of a qualitative rating scale of CA on
      MRI. MRI scans were performed in 50 consecutive patients (age range 19-81)
      admitted for an acute hemispheric ischemic stroke. CA was assessed on 2 occasions
      24 h apart, on axial T2-weighted sequences by 4 independent observers. We
      evaluated CA in 13 regions on a 0-3 scale. The sum of the subscores was called
      the CA score (range: 0-39). The level of agreement was expressed by kappa
      statistics as well as by analysis of variance for interexaminer reproducibility
      studies. The mean CA scores ranged from 2.8 to 11.0, indicating the low
      prevalence of CA in this sample. Complete agreement was reached in 41.7% during
      the first assessment and in 44.1% in the second assessment. The interobserver
      agreement was moderate in the first session (mean overall kappa: 0.48) and
      substantial in the second (mean overall kappa: 0.67). The intraobserver agreement
      was good for all raters (mean kappa: 0.65). Standardized to the range of the
      scale, standard deviations of the differences between CA scores of the 4 raters
      in the 2 sessions were 11.1 and 11.2%; within raters it was 4.4%. We conclude
      that the assessment of CA using this rating scale is possible in stroke patients.
      It provides regional atrophy measurements and is reproducible when performed by 1
      rater.

PMID- 8864707
TI  - Magnetic resonance volumetry of the cerebellum in epileptic patients after
      phenytoin overdosages.
AB  - The aim of this study was to evaluate the relationship between phenytoin
      medication and cerebellar atrophy in patients who had experienced clinical
      intoxication. Five females and 6 males, 21-59 years of age, were examined with a
      1.5-T whole-body system using a circular polarized head coil. Conventional spin
      echo images were acquired in the sagittal and transverse orientation. In
      addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences
      at a 1-mm slice thickness. The images were subsequently processed to obtain
      volumetric data for the cerebellum. Cerebellar volume for the patient group
      ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo
      data sets from 10 healthy male and 10 healthy female age-matched volunteers were
      used to compare cerebellar volumes. Using linear regression we found that no
      correlation exists between seizure duration, elevation of phenytoin serum levels
      and cerebellar volume. However, multiple regression for the daily dosage,
      duration of phenytoin treatment and cerebellar volume revealed a correlation of
      these parameters. We conclude that phenytoin overdosage does not necessarily
      result in cerebellar atrophy and it is unlikely that phenytoin medication was the
      only cause of cerebellar atrophy in the remaining patients. Quantitative
      morphometric studies of the cerebellum provide valuable insights into the
      pathogenesis of cerebellar disorders.

PMID- 8864708
TI  - Development of osteopenia in the hemiplegic finger in patients with stroke.
AB  - Previous studies have demonstrated that hip fractures in stroke patients occurred
      almost exclusively on the hemiplegic side. We examined the bone changes in the
      second metacarpal of the hemiplegic side in terms of microdensitometric indices
      in 93 stroke patients with hemiplegia. All six indices indicated a significant
      decrease in bone mass on the hemiplegic side compared with the contralateral
      side. Differences in the indices between the hemiplegic and contralateral sides
      were correlated well with the duration of the illness and Brunstrom's stage for
      finger, arm, and leg. The same degree of osteopenia occurred in both small
      capsular and large hemispheric lesions. The same osteopenia was demonstrated in
      paralyzed and immobilized patients with myopathy. Thus a combination of weakness
      and immobilization is thought to be responsible for the osteopenia in the
      hemiplegic metacarpal bone. The osteopenia noted in the second metacarpal in the
      affected limb may account for the fact that hip fractures in stroke patients
      occur almost exclusively on the hemiplegic side.

PMID- 8864709
TI  - Quantification of muscle strength in recessive myotonia congenita.
AB  - In order to quantify muscle strength in recessive myotonia congenita (MC) the
      peak and average peak torques (PT and APT, respectively) of knee flexion and
      extension of 19 MC patients were measured at speeds of 60 degrees/s and 200
      degrees/s. Muscle endurance was measured at a speed of 200 degrees/s. No
      differences were found between the patient and control groups for PT and APT
      values for flexion at the high speed, nor were there any differences between the
      patients and the controls for PT and APT measured at the low speed for knee
      flexion and extension or muscle endurance at the high speed. However, PT and APT
      values of the patients for extension at the high speed, 100 +/- 41 Nm (mean +/-
      SD) and 95 +/- 39, were significantly lower than those of the controls, 129 +/-
      43 and 124 +/- 42, respectively. There was no correlation between muscle strength
      or endurance and disease severity. The muscle strength of the patient group was
      diminished (p < 0.0001) during the beginning of the measurement at the high
      speed. The results suggest that after myotonic inhibition subsides the muscle
      strength of MC patients ranges within normal limits except in rapid and powerful
      motor activities.

PMID- 8864710
TI  - Effects of acyclovir on sensory axonal neuropathy, segmental motor paresis and
      postherpetic neuralgia in herpes zoster patients.
AB  - The effect of oral treatment with acyclovir (ACV) on sensory axonal neuropathy,
      segmental motor paresis and postherpetic neuralgia (PHN) was studied in 105
      patients with herpes zoster. Forty-seven patients were treated with ACV at a dose
      of 4 g/day in 5 doses for at least a week; the others did not undergo any kind of
      treatment. Electrodiagnostic examination of the nerves and muscles corresponding
      to the dermatomeric lesions was performed, including sensory and motor nerve
      conduction studies, blink reflex and electromyography (EMG). The patients treated
      with ACV showed a significant reduction in the number of cases in which there was
      electrophysiological evidence of axonal damage in afferent fibres of nerves
      arising from roots corresponding to affected dermatomes. The treated group also
      showed a smaller incidence of segmental motor neuritis, clinically evident or
      only detectable by EMG as denervation. However, there was no significant
      difference between groups as far as the incidence of PHN was concerned. Oral
      treatment with ACV therefore reduces peripheral sensory axonopathy due to
      ganglion damage and prevents the possibility of spread to anterior roots and
      spinal motoneurones. In this way it reduces the incidence of segmental motor
      neuritis, but does not reduce the incidence of PHN.

PMID- 8864711
TI  - Signal hyperintensities on brain magnetic resonance imaging in elderly depressed
      patients.
AB  - In a retrospective brain magnetic resonance imaging study, we evaluated the
      prevalence and severity of signal hyperintensities in 30 elderly depressed
      patients and 30 controls matched for age, sex and cerebrovascular risk factors. A
      semiquantitative scoring method was used to grade findings in T2-weighted and
      proton density images. The elderly depressed patients had more extended
      periventricular hyperintensities, especially in the frontal region (depressed vs.
      control, 87 vs. 57%, p < 0.05), pons (33 vs. 7%, p < 0.05) as well as
      hyperintensities in the putamen and globus pallidus (57 vs. 27%, p < 0.05). The
      third ventricle was more dilated in depressed patients than controls after
      adjustment for age and cerebrovascular risk factors. The global index for
      ventricular enlargement was correlated significantly (r = 0.36, p < 0.05) with
      the severity of the hyperintensity in depressed patients. Our results indicate
      that these hyperintensities, especially in the frontal region, pons and
      lenticular nuclei, and the dilatation of the third ventricle play an important
      role, through the frontal-subcortical circuits, in mood regulation of elderly
      depressed patients.

PMID- 8864712
TI  - Analysis of urinary pyridinoline and deoxypyridinoline in patients undergoing
      long-term anticonvulsant drug therapy.
AB  - Urinary pyridinoline and deoxypyridinoline were analyzed in 23 patients
      undergoing long-term anticonvulsant drug therapy and compared with those in an
      age-matched control group, which consisted of 218 healthy premenopausal women.
      Values of urinary pyridinoline and deoxypyridinoline in the patient group were
      significantly higher than those in the control group. However, mean serum levels
      of alkaline phosphatase in the patient group were within the control range. Our
      data demonstrate that bone resorption is accelerated by long-term anticonvulsant
      drug therapy and there may be an imbalance between bone resorption and bone
      formation in the patient group.

PMID- 8864713
TI  - EEG topography during insulin-induced hypoglycemia in patients with insulin
      dependent diabetes mellitus.
AB  - A group of young patients with insulin-dependent diabetes mellitus (n = 14; 8
      men, 6 women; 33.1 +/- 8.9 years) were examined by topographic EEG mapping under
      normoglycemic and hypoglycemic conditions (glucose levels after intravenous
      insulin injection down to 32.6 +/- 7.6 mg/dl). From the clinical aspect, 7 of
      them had a good and 7 had a poor awareness of hypoglycemia. During hypoglycemia,
      a decrease in alpha activity (p < 0.05), an increase in delta (p < 0.05), and
      especially in theta activity (p < 0.05) were found. The most sensitive parameter
      was the alpha/theta ratio. In the range of slight hypoglycemia (50-60 mg/dl) the
      increase in delta and theta activity showed a topographic maximum in lateral
      frontal regions. During deep hypoglycemia there was a topographic maximum of slow
      frequencies in posterior parts of the brain (centrotemporal to parieto-occipital
      regions). The differences between the group with good and with poor awareness of
      hypoglycemia were most pronounced during slight hypoglycemia in C3, C4, and Pz (p
      < 0.05). At lower glucose levels group distinction was no longer possible. These
      EEG changes correspond to a temporary organic brain syndrome.

PMID- 8864714
TI  - Clinical correlates of quantitative acoustic analysis in ataxic dysarthria.
AB  - The speech of 15 Taiwanese patients with cerebellar dysfunction and ataxic
      dysarthria was investigated utilizing techniques of acoustic analysis and
      instrumental measurement. Semiquantitative assessment of cerebellar function
      (SQACF) was also performed. The results of the acoustic analysis of the
      cerebellar speech were then correlated with the findings in the SQACF. The
      overlapping of voice onset time highly correlates with truncal ataxia as well as
      eye movement abnormality and eye-hand coordination. The prolongation of vowel
      duration also correlates significantly with tandem walking, dysdiadochokinesia
      and eye movement abnormality. The correlation of the speech function with other
      cerebellar motor functions provides further insight into the functional anatomy
      for cerebellar speech motor control. This study concludes that the midline
      structures-vermis and fastigial nucleus-seem to be the primary focus for the
      coordination of motor speech in the cerebellum.

PMID- 8864715
TI  - European Pentoxifylline Multi-Infarct Dementia Study.
AB  - A double-blind, placebo-controlled, parallel-group, multicentre study was
      conducted to evaluate the efficacy of pentoxifylline (Trental) in patients with
      multi-infarct dementia (MID) according to DSM-III-R criteria. Men and women aged
      45 years or older, with a Hachinski Ischemia Scale score > or = 7 and a Mini
      Mental State Examination (MMSE) score of 10-25 at entry, and computed tomographic
      evidence of vascular disease were enrolled. A total of 289 patients were
      randomised to receive either oral pentoxifylline 400 mg t.i.d. or placebo for 9
      months, and efficacy was assessed every 3 months. The primary outcome variable
      was the difference in scores between the two treatment groups, as measured on the
      Gottfries, Brane, Steen (GBS) scale. Secondary outcome variables included the
      scores achieved on the Sandoz Clinical Assessment Geriatric (SCAG) scale and
      MMSE, and a battery of psychological and other tests. The intention-to-treat
      analysis for patients completing the study (n = 239) showed a statistically
      significant difference in the total GBS score in favour of pentoxifylline
      (improvement of 3.5 points, p = 0.028). A significant difference in the total GBS
      score in favour of pentoxifylline was even almost achieved in the intention-to
      treat analysis for all evaluable patients (n = 269, improvement of 2.1 points, p
      = 0.065). It is concluded that treatment with pentoxifylline is beneficial for
      patients with MID, the global results of the GBS and SCAG scales being reinforced
      by significant improvements in those subscales specific for intellectual and
      cognitive function.

PMID- 8864716
TI  - Paraneoplastic opsoclonus-myoclonus syndrome and neurofibrosarcoma.

PMID- 8864717
TI  - Frontal lobe syndrome after a left genu capsular infarction.

PMID- 8864718
TI  - Isolated peripheral hypoglossal palsy caused by a kinking of the left vertebral
      artery (hypoglossal vertebral entrapment syndrome).

PMID- 8864719
TI  - Myasthenia gravis and sarcoidosis: report of 2 cases.

PMID- 8864720
TI  - Systemic lupus erythematosus related recurrent transverse myelitis in a patient
      with myasthenia gravis and multiple sclerosis.

PMID- 8864721
TI  - Acute inflammatory CNS disease after MDMA ('ecstasy').

PMID- 8864722
TI  - Advantages and shortcomings of experimental models of immune-mediated glomerular
      and tubulointerstitial diseases.

PMID- 8864723
TI  - Control of proximal tubular apical Na/Pi cotransport.
AB  - Two renal proximal tubular apical sodium-dependent transport systems for
      phosphate (Na/Pi cotransporter) have been identified. Recent studies demonstrated
      that the abundance of the type II Na/Pi cotransporter in the brush border is
      critical for the capacity of phosphate reabsorption. Evidence was obtained that a
      change of apical Na/Pi cotransporters may occur via endo/ exocytic processes and
      via protein-synthesis-dependent mechanisms involving altered transcription and/or
      stability of mRNA. In addition, acute control of apical Na/Pi cotransport may
      occur via the pH dependence and electrogenicity of the Na/Pi cotransporter.

PMID- 8864724
TI  - Goodpasture syndrome: selective removal of anti-alpha 3 (IV) collagen
      autoantibodies. A potential therapeutic alternative to plasmapheresis.
AB  - Anti-alpha 3(IV) collagen autoantibodies have been implicated in the pathogenesis
      of Goodpasture syndrome, an autoimmune disorder causing glomerulonephritis and
      pulmonary hemorrhage. Currently treatment involves removal of the entire IgG
      fraction of plasma by plasmapheresis or adsorption to protein A. The present
      study shows that the anti-alpha 3(IV)NC1 autoantibodies can be removed from
      plasma specifically and quantitatively by affinity chromatography utilizing
      either alpha 3 NC1 domain of bovine type IV collagen or recombinant alpha 3 NC1
      domain of human type IV collagen immobilized to agarose beads. This study shows
      the feasibility of using affinity chromatography, as an alternative to
      plasmapheresis, to exclusively remove the pathogenic autoantibodies from the
      plasma of patients with Goodpasture syndrome.

PMID- 8864726
TI  - Transforming growth factor-beta and its receptors in rabbit renal proximal
      tubules after uninephrectomy.
AB  - Transforming growth factor-beta (TGF beta) and its receptors were studied in
      proximal tubules isolated from rabbit renal cortex at different times after
      uninephrectomy (UNX). Scatchard analysis of TGF beta-binding data in proximal
      tubules from control kidneys revealed two types of binding sites, with Kd 21 and
      208 pM, and Bmax 33 and 104 fmol/mg protein, respectively. Kd values were similar
      in these animals at 1 or 2 weeks after either UNX or sham operation (SNX).
      However, Bmax increased in parallel with the observed increase in the protein/DNA
      ratio of the proximal tubules at 2 weeks after UNX. In contrast, [125I]-insulin
      binding per milligram of protein was lower in proximal tubules from
      uninephrectomized compared to sham-operated animals within the same time period.
      Affinity labeling of [125I]-TGF beta 1-binding sites in proximal tubules from
      either sham-operated or uninephrectomized rabbits displayed two labeled proteins
      with apparent molecular weights of > 143 and 43 kD. We found an increased TGF
      beta bioactivity in the conditioned medium of proximal tubules at 2 weeks
      following UNX. This protein increase was associated with an increased TGF beta 1
      mRNA expression in these tubules. In contrast, no significant changes in TGF beta
      bioactivity were observed in rabbit glomeruli conditioned medium or in rabbit
      urine at this time period after UNX. Our data indicate that hypertrophy of the
      proximal tubule is associated with an increased TGF beta production and a lack of
      downregulation of its receptors in this nephron portion.

PMID- 8864725
TI  - Lipopolysaccharide-induced glomerulonephritis develops in the absence of
      interferon-gamma signaling.
AB  - IFN gamma is a costimulator of macrophage activation and it plays an important
      role as a proinflammatory cytokine by upregulation of adhesion molecules and MHC
      antigens. In this study we tested the role of IFN gamma in a model of endotoxin
      induced glomerulonephritis. A systemic lupus-like disease was induced by
      injection of 50 micrograms bacterial LPS twice a week for 4 weeks in wild-type
      and in IFN gamma receptor-deficient (IFN gamma R-/-) mice. The renal cortex was
      examined by immunofluorescence and by light microscopy. LPS treatment induced an
      increase in serum levels of IgG and anti-dsDNA antibodies. A mild
      glomerulonephritis was characterized morphologically, but proteinuria was not
      observed. The main histological features of glomerulonephritis were an increase
      in ICAM-1 expression, deposition of immune complexes and of complement in the
      glomeruli, increased mesangial matrix and mesangial hypercellularity. The number
      of intraglomerular leukocytes, detected by MHC class-II and LFA-1 expression
      increased roughly 4-fold. All those alterations took place in a similar manner in
      wild-type and in IFN gamma R-/-mice. Therefore it is concluded that IFN gamma
      does not play an important role in the development of endotoxic
      glomerulonephritis.

PMID- 8864727
TI  - Relationship between alpha-smooth muscle actin expression and fibrotic changes in
      human kidney.
AB  - The alpha-smooth muscle (alpha-SM) actin isoform is expressed normally by
      vascular SM cells and by stromal fibroblastic cells in pathological conditions
      leading to fibrosis. In order to investigate the relation between kidney fibrosis
      and alpha-SM actin expression, we studied 51 renal biopsies from 45 patients: 30
      with various forms of glomerulonephritis; 1 with acute tubular necrosis; 1 with
      acute interstitial nephritis, and 13 renal transplant recipients. The presence of
      alpha-SM actin was examined by using anti-alpha SM-1, a mouse monoclonal antibody
      (IgG2 alpha) specific for alpha-SM actin. alpha-SM actin scores were estimated
      semiquantitatively, as were glomerulosclerosis and interstitial fibrosis. In
      acute tubular necrosis and in well-functioning grafts, alpha-SM actin expression
      was limited to vascular SM cells. In glomerular diseases, alpha-SM actin
      expression was upregulated in mesangial area in 25 of 36 biopsies, and even more
      frequently in the periglomerular and peritubular interstitium (34 of 36 cases,
      chi 2 = 7.6, P < 0.01). Whereas glomerular alpha-SM actin expression seemed to
      decrease as glomerulosclerosis progressed, there was a positive correlation
      between interstitial alpha-SM actin scores and the degree of interstitial
      fibrosis. Similarly, interstitial alpha-SM actin expression was found in acutely
      or chronically rejected kidneys, but not in well-functioning grafts. We conclude
      that upregulation of alpha-SM actin in the glomerulus indicates mesangial cell
      activation and is not always correlated with the degree of glomerulosclerosis. In
      contrast, interstitial upregulation of alpha-SM actin which indicates
      myofibroblast activation is correlated with the degree of interstitial fibrosis.

PMID- 8864729
TI  - Secondary tracheoesophageal puncture: factors predictive of voice quality and
      prosthesis use.
AB  - OBJECTIVE: To identify factors predicting prosthesis use and final speech quality
      in patients undergoing secondary tracheoesophageal puncture (TEP) for voice
      restoration alter laryngectomy. METHODS: We undertook a retrospective study of
      168 patients who underwent secondary TEP at the Cleveland Clinic between June
      1980 and October 1993. Factors examined were: patient demographics, extent of
      initial surgery, method of pharyngeal preparation, history of irradiation,
      insufflation test results, pharyngeal stricture, and concurrent medical
      conditions. Univariate and multivariate statistical analyses were performed to
      identify predictive factors. RESULTS: At last evaluation, 73.8% (124) of the
      patients were still using the prosthesis. Quality of speech was the only
      predictor of prosthesis use (p < .001). Phonation on the first day was achieved
      in 90% (151) of patients. Speech result improved significantly over the first 6
      months (p < .001). Univariate analysis found that the need for reconstruction at
      laryngectomy (p = .04), the presence of pharyngeal stricture (p = .001), and
      continued prosthetic use (p < .001) were associated with the speech result. There
      was no significant advantage to the lack of approximation of the pharyngeal
      constrictors (p = .31). Stepwise logistic regression showed that only the absence
      of pharyngeal stricture was associated with a better-quality voice (p = .001).
      CONCLUSION: Tracheoesophageal puncture is a reliable method for restoring voice
      after laryngectomy. Prosthesis use decreases with time, and good voice quality is
      the only predictor of continued prosthesis use. In this series the absence of
      pharyngeal stricture was the only significant predictor of good to excellent
      speech.

PMID- 8864728
TI  - Supplementation with L-2-oxothiazolidine-4-carboxylic acid, a cysteine precursor,
      does not protect against lipid peroxidation in puromycin aminonucleoside-induced
      nephropathy.
AB  - Lipid peroxidation in the kidney has been shown to precede proteinuria in
      puromycin aminonucleoside (PAN)-induced nephropathy. The aim of this study was to
      determine if L-2-oxothiazolidine-4-carboxylic acid (procysteine) would protect
      rats against PAN-induced nephrotoxicity. Male Sprague-Dawley rats were treated
      with procysteine (16 mg/100 g body weight i.p.) 24 h and 30 min prior to
      receiving a single injection of PAN (15 mg/100 g body weight i.v.) followed by
      procysteine in the drinking water (4 g/l). Control rats received procysteine
      alone (intraperitoneally and in drinking water) or PAN alone and then plain
      water. Proteinuria was not significantly different between PAN/ procysteine and
      PAN groups, reaching a maximum at day 14 and persisting at day 28. Lipid
      peroxidation was more severe in PAN/procysteine rats reaching a maximum at day 3
      (253 +/- 30 ng/mg protein) compared to day 5 in PAN rats (196 +/- 20 ng/mg
      protein). Procysteine alone did not modulate proteinuria over 28 days or lipid
      peroxidation over 7 days. GSH levels over 7 days were not elevated by procysteine
      and were virtually zero in PAN and PAN/procysteine rats. Focal glomerulosclerosis
      (FGS) was worse at day 28 in PAN/procysteine rats than in PAN rats (39 +/- 8.2
      vs. 23 +/- 4.5%; p < 0.05). This study shows that procysteine as a potential
      source of reducing equivalents does not protect against renal lipid peroxidation
      and FGS in this model. On the contrary, PAN/procysteine rats developed
      significantly more FGS through yet unknown mechanisms.

PMID- 8864730
TI  - Short-term versus long-term antimicrobial prophylaxis in oncologic head and neck
      surgery.
AB  - BACKGROUND: Although antimicrobial prophylaxis is mandatory in major clean
      contaminated oncologic surgery of the head and neck, both the choice of specific
      antimicrobial compounds and the treatment duration are still discussed. METHODS:
      A prospective, randomized trial was carried out to compare efficacy and
      tolerability of clindamycin-cefonicid administered for 1 day versus 3 days in
      reducing the rate of wound and systemic infections. The following potential risk
      factors for surgical wound infection were evaluated: type of surgery, stage of
      disease, preoperative tracheostomy, preoperative radiotherapy, and diabetes
      mellitus. RESULTS: One-hundred sixty-two patients were evaluable; 81 received 1
      day chemoprophylaxis, while the remaining 81 were treated according to the 3-day
      schedule. During the first 20 days after surgery, wound infections occurred in 2
      (2.5%) and 3(3.7%) patients, respectively, in the 1-day and 3-day treatment
      groups, so that no significant difference was found among the two evaluated
      chemoprophylaxis schedules. CONCLUSION: A 3-day schedule did not prove useful in
      preventing wound and systemic infections. All presumed risk factors were not
      associated with an increased rate of wound infections, although preoperative
      radiotherapy was associated with a greater severity of infections and a higher
      risk of late wound complications.

PMID- 8864731
TI  - Combined chemotherapy and radiotherapy versus surgery and postoperative
      radiotherapy for advanced hypopharyngeal cancer.
AB  - BACKGROUND: Although the standard therapy for locally advanced hypopharyngeal
      cancer remains surgery and postoperative radiotherapy (RT), alternative treatment
      approaches include induction chemotherapy and RT. The purpose of this
      retrospective study was to compare the long-term outcome of these treatments
      performed in a single institution. METHODS: Twenty-six patients with advanced,
      resectable, squamous cell carcinoma of the hypopharynx were treated with
      induction chemotherapy and definitive RT (group I), reserving laryngectomy for
      salvage. The induction phase of therapy consisted of 2-3 cycles of cisplatin
      based chemotherapy followed by conventional fractionated RT to doses of 66-70 Gy.
      The outcomes of this group of patients were compared with the outcomes of 30
      patients with hypopharyngeal cancer who were treated at our institution with
      surgery and postoperative RT (group II). The median follow-up times of the
      surviving patients in groups I and II were 5 and 9 years, respectively. RESULTS:
      The local recurrence-free survival at 5 years from the completion of therapy for
      group I was 50%, compared with 69% for group II (p = .41). Among patients with T3
      T4 primary tumors, the 5-year local control rates were 58% and 59% for groups I
      and II, respectively (p = .78). The likelihood of larynx preservation, free of
      local disease at 5 years for group I, was 52%. The 5-year neck recurrence-free
      survival for groups I and II were 47% and 69%, respectively (p = .66). Among
      patients with N2-N3 stage disease, the 5-year incidence of neck failure for
      groups I and II were 73% and 68%, respectively (p = .74). The 5-year distant
      metastases-free survival for groups I and II were 67% and 57%, respectively (p =
      .19). The 5-year disease-free survival rates for groups I and II were 30% and
      42%, respectively (p = .9). The 5-year overall survival rates for groups I and II
      were 15% and 22%, respectively (p = .65). CONCLUSIONS: Nonsurgical therapy for
      advanced stage hypopharyngeal cancer provides survivorship comparable with that
      achieved with standard approaches of surgery and postoperative RT. However,
      despite the therapy, the outcome is poor. Future studies will need to explore new
      treatment strategies in an effort to improve upon the outcome for this group of
      patients.

PMID- 8864732
TI  - Deep circumflex iliac artery free flap with internal oblique muscle as a new
      method of immediate reconstruction of maxillectomy defect.
AB  - BACKGROUND: A wide range of pedicled and free tissue transfer flaps have been
      described in the reconstruction of the complex maxillofacial defect, but no
      preferred reconstructive technique has so far emerged. The previous methods
      described may effectively close the oronasal fistula but reliable support for the
      cheek and orbit while providing a basis for an implant retained prosthesis is
      less likely to be achieved. METHODS: The methods of using the flap in low, high,
      and central maxillectomy defects as well as cases requiring orbital exenteration
      are described. RESULTS AND CONCLUSIONS: The deep circumflex iliac artery (DCIA)
      flap with internal oblique provides a reliable reconstruction for the
      maxillectomy as the fistula is closed with muscle which becomes epithelialized
      with minimal bulk. The large volume of bone available from the iliac crest can
      restore the facial contour, support the orbital contents, reconstruct the orbital
      rim, and provide sufficient bulk of bone for the placement of implants.

PMID- 8864733
TI  - Expression of galectins in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Galectins are carbohydrate-binding proteins thought to be important
      for cell growth and differentiation, whose expression is altered in some tumors
      with aggressive phenotype. Our objective was to evaluate the expression of
      galectins in head and neck squamous cell carcinoma (HNSCC). METHODS: Fourteen
      HNSCC cell lines and four primary tumor specimens were evaluated using
      immunoblotting, and immunohistochemical analysis was performed on 35 primary
      HNSCCs. RESULTS: Galectin-1 and galectin-3 were expressed in most HNSCC cell
      lines and primary tumor specimens. Galectin-1 was detected in the basal layer of
      normal adjacent mucosa, in connective tissue stroma, and at the periphery of
      invasive tumor islands. Galectin-3 localized to superficial mucosal layers, and
      adjacent to keratin pearls in invasive carcinoma. CONCLUSIONS: Galectins are
      manifested in HNSCC tumors and are localized to the cell surface, where they may
      participate in cellular interactions. The expression pattern of galectins appears
      to be associated with degree of squamous differentiation, suggesting a potential
      role for galectins as biologic and differentiation markers in HNSCC.

PMID- 8864734
TI  - Nuclear DNA content and p53 immunostaining in metachronous preneoplastic lesions
      and subsequent carcinomas of the oral cavity.
AB  - BACKGROUND: Clinical evaluation of preneoplastic lesions of the oral cavity is
      difficult. Histopathologic grading of dysplasias shows large variability and does
      not give reliable information concerning the risk for progression to cancer.
      METHODS: DNA image cytometry and p53 immunostaining were performed to describe
      the pattern of DNA aberration and p53 overexpression in confined preneoplastic
      lesions and in the subsequent carcinomas developing at the same site in 20
      patients. RESULTS: Hyperplastic and/or inflammatory lesions showed a diploid DNA
      pattern in 81% of the cases and 23% were p53-positive. Dysplastic preneoplastic
      lesions showed a nondiploid/ aneuploid DNA pattern in 73% and 64% were p53
      positive. The subsequent invasive carcinomas were nondiploid/aneuploid in 86% and
      p53-positive in 69% of cases. CONCLUSIONS: Analysis of nuclear DNA content and
      p53 immunostaining appears to be useful as an adjunct to histopathology in the
      evaluation of true precancerous lesions.

PMID- 8864735
TI  - Epithelial dysplasia and squamous cell carcinoma of the Wistar rat palatal
      mucosa: 4NQO model.
AB  - BACKGROUND: The carcinogen 4-nitroquinoline 1-oxide (4NQO) has been used in
      several studies concerning experimental oral carcinogenesis to induce squamous
      cell carcinoma in the palatal mucosa of rats, whereas limited attention has been
      paid to preceding premalignant mucosal changes. The aim of this study was to
      describe the macroscopic and microscopic changes of the rat palatal mucosa
      treated with 4NQO as a function of the application time of this carcinogen.
      METHODS: The carcinogen 4NQO was applied to the palatal mucosa of male Wistar
      rats three times a week for 2-26 weeks. The Epithelial Atypia Index (EAI) was
      used to quantify the degree of dysplasia induced by the application of 4NQO for
      various time intervals. RESULTS: This study shows that the EAI increases as a
      function of the application time. As soon as 2 weeks following application of the
      carcinogen, dysplastic alterations in the mucosa were observed. The extent and
      grade of the dysplastic changes increased with time. At week 26, squamous cell
      carcinoma developed. In rats in which the application of 4NQO was discontinued
      earlier, the application period appeared to be in inverse proportion to the
      latency period i.e., the period between the last application of the carcinogen
      and the first clinical sign of squamous cell carcinoma. This emphasizes the
      premalignant character of the induced epithelial changes, because in all the rats
      squamous cell carcinoma eventually developed. CONCLUSIONS: From this study, we
      concluded that the 4NQO rat palate model is a proper model in which both
      premalignant epithelial lesions and squamous cell carcinoma of the oral mucosa
      can be studied.

PMID- 8864736
TI  - Intracranial inverting papilloma.
AB  - BACKGROUND: Inverting papillomas usually originate from the lateral wall of the
      nose and sporadically from the ethmoid, maxillary, sphenoid, or frontal sinuses.
      Intracranial extension and dural penetration is rare and often associated with
      recurrent disease that has degenerated into squamous cell carcinoma. A case of
      inverting papilloma with dural penetration in the absence of malignant
      degeneration has prompted an investigation into the incidence and treatment of
      dural invasion by benign inverting papilloma. METHODS: A literature search
      revealed 1468 cases of inverting papilloma. A detailed analysis was performed to
      obtain data on the incidence of intracranial invasion. RESULTS: Of the 1468
      cases, 5 were noted to be associated with intracranial extension without
      histologic evidence of malignancy (0.34%). Treatment consisted of surgery alone
      in 3, radiotherapy in 1, and combined therapy in the last patient. Dural invasion
      was documented histopathologically in one case. CONCLUSION: Intracranial
      extension and dural penetration of benign inverting papilloma is extremely rare,
      and a uniform treatment plan has not been established. Further investigation is
      necessary in the pathophysiology and management of intracranial inverting
      papilloma.

PMID- 8864737
TI  - Cytomegalovirus causing necrotizing laryngitis in a renal and cardiac transplant
      recipient.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is a common opportunistic pathogen in
      transplant recipients; however, cytomegaloviral laryngitis is extremely rare.
      METHODS: We present a case of disseminated CMV infection and ulcerating
      necrotizing laryngitis situated in the subglottis of an immunocompromised patient
      with a renal and cardiac transplant. The patient was initially seen with
      discomfort in the throat. RESULTS: Physical examination of the head and neck,
      fiberoptic laryngoscopy, and CT scan of the larynx were normal. Histopathology of
      a laryngeal ulcer in the subglottic region showed intranuclear and
      intracytoplasmic bodies. Immunoperoxidase stain and in situ hybridization studies
      were positive for CMV. CONCLUSIONS: In immunosuppressed patients with persistent
      throat symptoms, the systematic exploration of larynx and bronchus is necessary
      to rule out the presence of opportunistic infections.

PMID- 8864738
TI  - Myxoma of the maxilla: a case with extremely aggressive biologic behavior.
AB  - BACKGROUND: Osseous "bone-derived" myxoma is a benign, slow-growing, locally
      invasive tumor that is found exclusively in the facial skeleton. Although
      recurrence is frequent, uncontrolled growth is not classic. METHODS AND RESULTS:
      We report the case of a patient with myxoma of the maxilla in which the growth of
      the myxoma was so invasive that it resulted in destruction and deformation of the
      facial skeleton even after repeated resections. Eventually, destruction and
      infiltration of the skull base with a fatal outcome was the result. CONCLUSIONS:
      This case of locally aggressive myxoma of the maxilla illustrates the need for a
      correct primary treatment of this benign tumor. Although complete resection may
      result in a significant functional and aesthetic mutilation, incomplete primary
      removal results in high recurrence rates. Therefore, a radical primary resection
      of the tumor with maximal preservation of surrounding anatomic structures is
      necessary. Follow-up should be meticulous and based upon regular clinical and
      radiographic examinations.

PMID- 8864740
TI  - Sex differentiation and ovarian function. An overview.

PMID- 8864739
TI  - Fibroinflammatory pseudotumor of the submandibular gland.
AB  - BACKGROUND: Fibroinflammatory pseudotumors infrequently involve the major
      salivary glands. Much more is known regarding the clinical behavior of orbital
      pseudotumors, especially their steroid responsiveness. METHODS: A case of
      fibroinflammatory pseudotumor involving the submandibular gland is presented with
      its preoperative cytologic and computed tomographic scan features. The lesion had
      a dramatic response to steroids for residual disease. CONCLUSIONS: If
      preoperative cytologic features of benign spindle cells with an inflammatory
      component seen on fine-needle aspiration raise the possibility of
      fibroinflammatory pseudotumor, then responsiveness to high-dose steroids may
      preclude the need for more-extensive surgery.

PMID- 8864741
TI  - Analysis of the testis-determining gene SRY in patients with XY gonadal
      dysgenesis.
AB  - The sex-determining region of the Y chromosome (SRY) encodes a gene that has many
      of the properties expected to the testis-determining factor. XY gonadal
      dysgenesis is characterized by streak gonads in phenotypic females who lack the
      somatic abnormalities and short stature associated with Turner's syndrome. We
      have examined four patients with XY gonadal dysgenesis for the presence and
      absence of SRY and the DNA sequence of the gene. The results showing that one was
      negative for SRY and another had a mutation within the gene have confirmed the
      etiological role of SRY in XY gonadal dysgenesis. However, the other two patients
      with short stature had apparently normal SRY. DNA sequencing of the SRY gene
      showed 100% nucleotide sequence identity with the reported cloned sequence. Sex
      reversal in two of the present cases may be due to mutation at a locus other than
      SRY in the sex-determining pathway, a gene potentially involved in the
      determination of human sexual constitution.

PMID- 8864742
TI  - Role of c-mos proto-oncogene product in the regulation of mouse oocyte
      maturation.
AB  - The c-mos proto-oncogene product (Mos) is essential for the initiation of oocyte
      maturation, for the suppression of DNA synthesis during meiosis, and for the
      second metaphase arrest in Xenopus. To clarify the function of Mos in mice, c-mos
      deficient mice were generated by gene targeting. We cultured oocytes from c-mos
      deficient females to determine the role of Mos in oocyte maturation. c-mos
      deficient oocytes matured normally to the second metaphase, but were activated
      without fertilization. Thus, prevention of parthenogenetic activation might be an
      ultimate biological function of Mos in animal oocytes.

PMID- 8864743
TI  - Abnormalities of sex differentiation.
AB  - Sex differentiation is determined by a cascade of events proceeding from
      chromosomal sex to the completion of sexual maturation at puberty. Many factors
      involved in this cascade have been identified. Here we focus on DAX-1, androgen
      receptor and cytochrome P450c17, and discuss their functions in sex
      differentiation. We analyzed the DAX-1 genes of two unrelated Japanese patients
      with congenital adrenal hypoplasia and hypogonadotropic hypogonadism using PCR
      amplification of genomic DNA and complete exonic sequencing, and established that
      congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not
      only inherited but also de novo mutation in the DAX-1 gene. Androgen
      insensitivity syndrome (AIS) is a good model to clarify the relationship between
      the structure and function of androgen receptor, the androgen receptor gene
      mutation and clinical phenotype. We analyzed 15 cases of AIS and demonstrate the
      structural and functional relationships of the androgen receptor. We have
      sequenced the CYP17 (P450c17) gene in DNA from several patients with 17 alpha
      hydroxylase deficiency, reconstructed the mutations in a human P450c17 cDNA and
      expressed the mutant P450c17 in COSl cells to characterize the kinetic properties
      of 17 alpha-hydroxylase and 17,20-lyase activities. The molecular bases of cases
      clinically reported as 17 alpha-hydroxylase deficiency have turned out to be
      complete or partial combined deficiencies of 17 alpha-hydroxylase/17,20-lyase.

PMID- 8864744
TI  - The Y chromosome region essential for spermatogenesis.
AB  - We analyzed DNA from 153 Japanese men with azoospermia or severe oligozoospermia
      whose Y chromosomes were cytogenetically normal. A total of 23 loci on the Y
      chromosome were examined: 15 loci within interval 6 including YRRM1 and DAZ, and
      8 loci outside interval 6. Microdeletions were observed in 20 individuals. All
      deletions involved at least one locus within interval 6. The YRRM1 gene deletion
      was found in 4 patients, of whom 2 also lacked the SMCY gene. The remaining 16
      individuals shared the absence of 10 loci between DYS7C and DYS239 including the
      DAZ gene. Among them, 13 were azoospermic while 3 showed a little sperm
      production, indicating that the common deletion resulted in phenotypic diversity.
      Since there is no region commonly deleted in all patients, azoospermia caused by
      deletion of the Y chromosome long arm may be genetically heterogeneous.

PMID- 8864745
TI  - Granulosa cells express integrin alpha 6: possible involvement of integrin alpha
      6 in folliculogenesis.
AB  - To identify differentiation antigens of granulosa cells, we have raised two
      monoclonal antibodies against porcine granulosa cells (POG-2 antibody) and human
      granulosa cells (OG-1 antibody). Analysis of N-terminal amino acid sequences of
      purified OG-1 and POG-2 antigens revealed that they were identical to human
      integrin alpha 6 and its porcine homolog, respectively. An immunohistochemical
      study showed that integrin alpha 6 was highly expressed on granulosa cells in
      preovulatory follicles in the human ovary, whereas it was highly expressed on
      granulosa cells in small follicles in the porcine ovary. As a common
      characteristic of integrin alpha 6 expression in both ovaries, granulosa cells
      located in inner layers, which are not in contact with the basal lamina,
      expressed integrin alpha 6 on the cell surface. This expression profile suggests
      that the interaction between integrin and extracellular matrices occurs in the
      granulosa cells located in inner layers. This cell surface interaction is
      reported to modulate soluble signals to the cells. Since the expression of
      integrin alpha 6 on inner-layer granulosa cells is related to stages of
      differentiation, this interaction may be involved in folliculogenesis.

PMID- 8864746
TI  - Physiological role of insulin-like-growth-factor-binding protein-4 in human
      folliculogenesis.
AB  - Insulin-like growth factor (IGF)-I and IGF-II, and their binding proteins
      (IGFBPs) have been demonstrated to play important roles in follicular development
      as intraovarian regulators. Previous studies have demonstrated that the
      follicular fluid of atretic follicles contains high levels of IGFBP-2 and IGFBP
      4, which are known to inhibit the action of IGFs. In this study, we identified
      IGFBP-4 protease activity in the follicular fluid of developing but not atretic
      follicles. To elucidate the regulation mechanism of IGFBP-4 proteolytic activity
      in the ovary, cultured luteinized granulosa cells (GCs) were incubated with
      various hormones, and proteolyzed IGFBP-4 in the medium was analyzed. IGFBP-4
      proteolytic activity was increased when GCs were incubated with IGFs, estradiol
      or follicle-stimulating hormone (FSH) but not with testosterone. We also showed
      that IGFBP-4 inhibited IGF-1-induced estradiol release by GCs while proteolyzed
      IGFBP-4 did not. These results suggest that human luteinized GCs produce IGFBP-4
      protease, and that FSH and IGFs may stimulate folliculogenesis by modulating
      IGFBP-4 degradation in the ovary.

PMID- 8864748
TI  - Role of macrophages in ovarian follicular development.
AB  - The effects of macrophages on granulosa cell proliferation were examined using
      gonadotropin-primed immature female rats and osteopetrotic (op/op) mice, a model
      defective in monocyte-macrophage lineage cells. Macrophages were found in the
      follicles at various developmental stages in rats and mice. The labeling index
      with [3H]thymidine of cultured rat granulosa cells was maximal when they were
      cultured with peritoneal macrophages at a macrophages:granulosa cell ratio of
      0.01. This ratio was similar to those in rat preantral and antral follicles in
      vivo. In op/op mice, the number of developing follicles was markedly reduced, but
      increased after daily macrophage-colony-stimulating factor (M-CSF)
      administration. In the antral follicles of op/op mice, both granulosa cells and
      macrophages were significantly decreased in number but were increased after M-CSF
      treatment. Double immunohistochemical staining revealed that epidermal growth
      factor (EGF)-positive cells were macrophages in the developing rat follicles.
      These findings suggest that macrophages are located in the developing follicles
      and participate in promoting granulosa cell growth through a paracrine mechanism
      by secreting EGF and other cytokines.

PMID- 8864747
TI  - Regulation of follicle-stimulating hormone receptor.
AB  - The acquisition of follicle-stimulating hormone (FSH) receptors during
      folliculogenesis is believed to be a key event in follicle development. We have
      examined the effects of FSH and activin on FSH receptor mRNA in cultured rat
      granulosa cells. Treatment of granulosa cells with FSH resulted in transient
      suppression of the FSH receptor mRNA levels 2-6 h after treatment, with
      subsequent recovery at 24 h. We could not detect a similar effect on FSH receptor
      mRNA by 8-bromoadenosine 3,5-cyclic monophosphate, which continuously stimulated
      FSH receptor mRNA over a similar time course. On the other hand, stimulation of
      the protein kinase C (PKC) pathway with phorbol myristate acetate mimicked the
      time course of the effects of FSH on the levels of FSH receptor mRNA. Taken
      together, these results suggest that the cAMP cascade may increase the mRNA
      levels of FSH receptor and, at the same time, the other cascade, PKC, may
      decrease FSH receptor mRNA levels. To further investigate the role of activin in
      the regulation of granulosa cell function, we studied the effect of activin on
      FSH receptor mRNA levels. Compared to the control, treatment with activin (100
      ng/ml) increased FSH receptor mRNA in a time-dependent manner with a maximum
      circa 4-fold increase at 24 h. Treatment of granulosa cells with activin (20-300
      ng/ml) for 24 h increased FSH receptor mRNA in a dose-dependent manner to a
      maximum circa 4-fold increase at concentrations of 100-300 ng/ml. Although
      follistatin alone had no detectable effect on FSH receptor mRNA levels,
      combination of follistatin (0-200 ng/ml) with activin (100 ng/ml) caused a
      significant reduction in the levels of activin-induced FSH receptor mRNA in a
      dose-dependent manner.

PMID- 8864749
TI  - Use of von Willebrand factor promoter to transduce suicidal gene to human
      endothelial cells, HUVEC.
AB  - Angiogenesis is an essential component of multifactorial carcinogenesis and thus
      a potential target of therapeutic intervention. To develop a novel cancer gene
      therapy strategy based on suppression of tumor angiogenesis, we examined the
      feasibility of targeting and preferential killing of proliferating endothelial
      cells by use of the von Willebrand factor (vWf) promoter and herpes simplex virus
      thymidine kinase gene (HSV-TK). Based on previous reports on the vWf promoter, we
      tested two putative vWf promoter regions. The luciferase assay showed that the
      shorter region, which encompasses most of the first noncoding exon, had stronger
      activity in endothelial cells. Although the promoter activity was low when
      employed as an internal promoter for retroviral and adenoviral vectors,
      endothelial cell specificity was suggested; the promoter, when used to drive the
      HSV-TK gene, could preferentially suppress endothelial cell growth in the
      presence of prodrug ganciclovir, suggesting the feasibility of designing an anti
      angiogenesis gene therapy using the vWf promoter and the suicide gene/prodrug
      strategy.

PMID- 8864750
TI  - Mice with adenine phosphoribosyltransferase deficiency develop fatal 2,8
      dihydroxyadenine lithiasis.
AB  - Deficiencies in different steps of purine metabolism give rise to a number of
      human inherited disorders. Lesch-Nyhan syndrome is a severe neurological
      disorder, caused by a deficiency in the purine salvage enzyme hypoxanthine
      phosphoribosyltransferase (HPRT). HPRT-deficient mice have been generated, but
      have proved to be an unsuccessful model of the human disease. We have suggested
      that this may be due to a greater dependency in rodents on the other purine
      salvage enzyme, adenine phosphoribosyltransferase (APRT). We have generated an
      APRT-deficient mouse line by gene targeting, with a phenotype that closely
      resembled the symptoms of APRT deficiency in man. APRT null mice were viable, but
      90% died prematurely before 6 months of age, displaying highly abnormal kidney
      morphology, with pathology characteristic of tubule obstruction. These mice have
      elevated urinary levels of adenine and 2,8-dihydroxyadenine, a highly insoluble
      adenine derivative, plus birefringent crystalline deposits and calculi within
      tubules throughout the kidney. A standard therapy for APRT-deficient human
      patients is the administration of the xanthine oxidase inhibitor, allopurinol.
      This has proved an effective therapy for APRT null mice, preventing accumulation
      of 2,8-dihydroxyadenine and much of the resultant renal obstruction, allowing us
      to establish a breeding line. We believe that these mice should provide a useful
      model for further study of APRT deficiency in humans. Furthermore, by generating
      APRT and HPRT double mutants, we will be able to test our hypothesis that both
      genes must be inactivated in mice before a model for Lesch-Nyhan syndrome can be
      obtained.

PMID- 8864751
TI  - In vitro and in vivo hepatoma cell-specific expression of a gene transferred with
      an adenoviral vector.
AB  - Recombinant adenoviruses are widely used for the transfer of foreign genes into
      various mammalian cells. However, the utilization of these vectors for cancer
      gene therapy requires the specific and efficient expression of the transferred
      gene in tumor cells. To obtain targeted expression in hepatoma cells, we
      constructed recombinant adenoviral vectors containing transcriptional elements
      from either the rat alpha-fetoprotein (AFP) or the human insulin-like growth
      factor II (IGFII) genes driving expression of the nuclear beta-galactosidase gene
      (nls lacZ). In vitro infection revealed that the AFP but not the IGFII
      transcriptional regulatory sequence controlled nls lacZ expression specifically
      in hepatoma cells. The same specificity was obtained in vivo in subcutaneous
      human hepatic tumors generated by engraftment of Huh7 hepatoma cells in nude mice
      as well as in primary liver tumors developed in rats and mice. No marker gene
      expression was detectable after AFP-nls lacZ gene transfer to normal rat liver
      parenchyma despite evidence for the presence of DNA encoding the nls lacZ gene.
      However, in vivo experiments with primary liver tumors in rats and mice also
      revealed that primary hepatoma cells were poorly infected by adenoviral vectors.
      Peritumoral and normal tissues were infected efficiently by adenoviral vectors.
      We conclude that hepatoma cell-specific expression of a transgene can be achieved
      with AFP regulatory sequences but that adenoviral vectors may not be the
      preferable vector for transferring genes in vivo in primary liver tumors.

PMID- 8864752
TI  - Intra- and extracellular immunization against HIV-1 infection with lymphocytes
      transduced with an AAV vector expressing a human anti-gp120 antibody.
AB  - Recently, we developed a novel anti-HIV-1 approach by transducing an anti-gp120
      antibody gene into lymphocytes, resulting in the resistance to HIV-1 infection by
      the combined intra- and extracellular binding activities of the neutralizing
      antibody. To extend this study, we improved the co-expression of the heavy and
      light chains of the Fab105 fragment of the anti-gp120 antibody F105 by using an
      internal ribosome entry site (IRES) sequence. The Fab105 expression cassette was
      then cloned into an adeno-associated virus (AAV) shuttle vector, and encapsidated
      recombinant AAV-Fab105 vectors were produced. The Fab105 antibody gene was shown
      to be transduced into human lymphocytes by using the recombinant AAV viruses. The
      transduced lymphocytes were able to produce and secrete the Fab105 fragments,
      while maintaining their normal morphology, growth rates, and responsiveness to
      mitogen stimulation. The infection of several primary HIV-1 patient isolates was
      effectively blocked in the transduced lymphocytes. This study indicates that the
      combined intra- and extracellular immunization approach may be useful for the
      treatment of HIV-1-infected patients.

PMID- 8864753
TI  - Retroviral infection is limited by Brownian motion.
AB  - Replication-defective retroviruses are frequently used as gene carriers for gene
      transfer into target cells. Here we show that the short half-lives of
      retroviruses limit the distance that they can effectively travel in solution by
      Brownian motion, and thus the possibility of successful gene transfer. This
      physiochemical limitation can be overcome, and effective contact between the
      retroviral gene carrier and the target cell can be obtained, by using net
      convective flow of retrovirus-containing medium through a layer of target cells.
      Using model cell lines (NIH-3T3 and CV-1), it was shown that gene transfer rates
      can be increased by more than an order of magnitude using the same concentration
      infection medium. High transduction rates could be obtained even in the absence
      of polycations, such as Polybrene, which heretofore have been required to achieve
      reasonable transduction rates. This development may play an important role in
      realizing human gene therapy.

PMID- 8864754
TI  - Particle-mediated gene transfer of granulocyte-macrophage colony-stimulating
      factor cDNA to tumor cells: implications for a clinically relevant tumor vaccine.
AB  - The necessity for prolonged tissue culture manipulations limits the clinical
      application of many form of gene therapy in patients with malignancies. We
      hypothesized that granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA
      in a plasmid expression vector could be effectively introduced into resting tumor
      cells, without the need for tissue culture propagation prior to or following
      transfection, and that efficient expression of transgenic GM-CSF by the
      transfected tumor cells would confer an effective immune response against tumors.
      GM-CSF cDNA in expression vectors was coated onto gold particles and accelerated
      with a gene gun device into mouse and human tumor cells. Human tumor tissue
      transfected within 4 hr of surgery produced significant levels of transgenic
      human GM-CSF protein in vitro. Human GM-CSF was readily detectable in serum and
      at the injection site following subcutaneous implantation of these transfected
      tumor cells into nude mice. Transfected and irradiated murine B16 melanoma cells
      produced > or = 100 ng/ml murine GM-CSF/10(6) cells per 24 hr in vitro for at
      least 10 days. The antitumor efficacy of this nonviral approach was tested using
      irradiated B16 tumor cells that were transfected with mGM-CSF cDNA and injected
      into mice as tumor "vaccine". Subsequent challenge of these mice with
      nonirradiated, nontransfected B16 tumor cells showed that 58% of the animals wer
      protected from the tumor by the prior vaccine treatment. In contrast, only 2% of
      control animals were protected by prior treatment with irradiated B16 cells
      transfected with the vector containing the luciferase gene. These results suggest
      that particle-mediated transfection of fresh tumor explants with cytokine cDNA is
      an effective and clinically attractive approach for cancer therapy.

PMID- 8864755
TI  - RANTES secretion by gene-modified tumor cells results in loss of tumorigenicity
      in vivo: role of immune cell subpopulations.
AB  - An immunogenic murine fibrosarcoma cell line was genetically modified to express
      and produce the human RANTES chemokine stably. In in vitro chemotaxis assays
      purified recombinant human RANTES as well as human RANTES secreted by the
      modified murine tumor cells were strongly chemoattractant for mouse CD8+ /Thy-1+
      tumor-infiltrating lymphocytes (TIL). RANTES production did not alter the growth
      of these cytokine gene-modified tumor cells in vitro, but injection of RANTES
      secreting cells resulted in the abolition of the ability of those cells to form
      solid tumors in vivo. The growth of tumors could be restored by co-administration
      of monoclonal antibodies that inhibit the function of various subsets of immune
      cells. For example, depletion of CD8+ T cells by antibody administration resulted
      in complete restoration of solid tumor formation by RANTES-secreting cells,
      whereas depletion of the CD4+ T cell population resulted in a partial restoration
      of tumor formation. Additionally, administration of an anti-CR3 monoclonal
      antibody known to inhibit the in vivo migration of macrophages also completely
      restored the tumorigenicity of RANTES-secreting fibrosarcoma cells. Thus, the
      human RANTES chemokine can abolish tumorigenicity of an immunogenic fibrosarcoma
      in an in vivo murine model, and this process is mediated by various
      subpopulations of immune effector cells.

PMID- 8864756
TI  - Cyclophosphamide diminishes inflammation and prolongs transgene expression
      following delivery of adenoviral vectors to mouse liver and lung.
AB  - Immune responses to adenovirus-mediated gene transfer contribute to the problems
      of transient recombinant gene expression, inflammation, and difficulties with
      vector readministration. Activation of CD4+ T cells is required for full
      realization of effector function of both CD8+ T cells (i.e., cytotoxic T cells)
      and B cells (i.e., neutralizing antibody). We evaluate in this study the
      effectiveness of a short course of high-dose cyclophosphamide to block immune
      responses in mice administered vector into lung and liver of C57BL/6 mice.
      Administration of cyclophosphamide with vector directed to liver blocked
      activation and mobilization of both CD4+ and CD8+ T cells. As a result, transgene
      expression was prolonged, inflammation was reduced, and, at the higher doses of
      cyclophosphamide, formation of neutralizing antibody was prevented and the vector
      was successfully readministered. Similar studies in the lung demonstrated an
      effective blockade of T and B cell responses. In contrast to the liver, where it
      was easier to stabilize transgene expression than to prevent neutralizing
      antibody, cyclophosphamide prevented the formation of neutralizing antibodies at
      all doses in the lung, whereas stabilization of transgene expression was only
      achieved at the highest dose. These experiments begin to define the parameters by
      which cyclophosphamide could be used as an adjunct in gene therapy.

PMID- 8864757
TI  - Regional delivery of an adenovirus vector containing the Escherichia coli
      cytosine deaminase gene to provide local activation of 5-fluorocytosine to
      suppress the growth of colon carcinoma metastatic to liver.
AB  - To evaluate the hypothesis that regional delivery of an adenovirus vector
      containing the Escherichia coli cytosine deaminase gene (AdCMV.CD) together with
      systemic 5-FC could suppress the growth of metastatic colon cancer in the liver,
      the AdCMV.CD vector was injected 0.8-1 cm from the site of a human colon cancer
      tumor in the livers of nude mice. The growth of the human colon cancer cells was
      quantified by dot blot analysis of genomic DNA extracted from tumor-bearing
      liver, hybridized with a human-specific Alu probe. The combination of regional
      AdCMV.CD plus systemic 5-fluorocytosine (5-FC) suppressed the growth of the
      metastatic tumors over the 21 days of evaluation following vector administration.
      Histologic evaluation showed necrosis at the site of the tumor in the livers of
      mice treated with AdCMV.CD/5-FC, but not in control groups. Evaluation of the
      potential toxicity of AdCMV.CD plus 5-FC on the normal liver showed only mild,
      self-limited dose-related inflammation, with no deaths. These data suggest that
      the regional administration of AdCMV.CD together with systemic 5-FC may be a safe
      and effective strategy to suppress the growth of metastases of colorectal
      carcinoma in the liver.

PMID- 8864758
TI  - Gluconoylated and glycosylated polylysines as vectors for gene transfer into
      cystic fibrosis airway epithelial cells.
AB  - To provide an alternative to viral vectors for the transfer of genes into airway
      epithelial cells in cystic fibrosis (CF), a novel set of substituted polylysines
      were employed. Polylysine was partially neutralized by blocking a number of
      positively charged residues with gluconoyl groups. In addition, polylysine was
      substituted with sugar residues on a specified number of amino groups. Using the
      gluconoylated polylysine as vector, the pCMVLuc plasmid gave high expression of
      the reporter gene luciferase in immortalized CF/T43 cells. The luciferase
      activity was 75-fold greater in the presence of 100 microM chloroquine.
      Luciferase gene expression persisted at high levels for up to at least 120 hr
      following transfection. Glycosylated polylysines/pCMVLuc complexes were compared
      to the gluconoylated polylysine/pCMVLuc complex and beta-Gal-, alpha-Glc-, and
      Lac-substituted polylysines gave 320%, 300%, and 290%, respectively, higher
      expression of the reporter gene luciferase. Luciferase expression ranged from 35
      to 2 ng of luciferase per milligram of cell protein in the order: beta-Gal =
      alpha-Glc = Lac > alpha-Gal = Rha = Man > beta-GalNAc > alpha-GalNAc = alpha-Fuc,
      suggesting that the transfection efficiency is sugar dependent. Most importantly,
      in primary cultures of both CF and non-CF airway epithelial cells grown from
      tracheal tissue explants, lactosylated polylysine gave uniformly high expression
      of luciferase. The glycosylated polylysines provide an attractive nonviral
      approach for the transfer of genes into airway epithelial cells.

PMID- 8864759
TI  - Retrovirus-mediated gene transfer of 6-pyruvoyl-tetrahydropterin synthase
      corrects tetrahydrobiopterin deficiency in fibroblasts from hyperphenylalaninemic
      patients.
AB  - Tetrahydrobiopterin (BH4) deficiency, a variant form of hyperphenylalaninemia
      with progressive neurological dysfunction, is primarily caused by autosomal
      recessive mutations in the gene encoding the 6-pyruvoyl-tetrahydropterin synthase
      (PTPS). PTPS is a biosynthetic enzyme for the BH4 co-factor, and its deficiency
      is associated with a malfunction of the phenylalanine catabolism in the liver and
      a lack of biogenic amine neurotransmitters dopamine and serotonin in the brain.
      We have previously isolated the wild-type PTPS cDNA and identified several
      mutations responsible for a decreased enzyme in patients. This study reports the
      in vitro correction of BH4 deficiency by using retrovirus mediated transfer of
      the PTPS cDNA into primary fibroblast cultures established from different
      patients. The Bing packaging cell line was used for amphotropic virus production.
      Following PTPS gene transfer, stimulation with cytokines restored biosynthesis of
      BH4 in originally defective cells to values comparable to those of heterozygous
      fibroblasts from clinically healthy subjects. These results not only provide a
      direct proof that the mutations in PTPS were causative for the mutant phenotype,
      but they are also the first step toward gene therapy as a potential alternative
      approach to treat BH4 deficiency.

PMID- 8864760
TI  - Myoblast gene therapy in canine mucopolysaccharidosis. I: Abrogation by an immune
      response to alpha-L-iduronidase.
AB  - Three dogs with deficiency of the lysosomal enzyme alpha-L-iduronidase were
      treated by gene replacement therapy targeted at muscle. Direct intramuscular
      injections of plasmid encoding the alpha-L-iduronidase gene cDNA resulted in no
      detectable enzyme production, but may have resulted in immunologic sensitization
      to iduronidase protein, which the dogs lack totally. Myoblasts were grown from
      skeletal muscle biopsies and transduced with a retroviral vector containing the
      canine gene under control of the muscle creatine kinase enhancer. Several hundred
      fold overexpression of enzyme production occurred in cultured cells; however,
      following reintroduction of the cultured cells into dogs, enzyme production
      declined rapidly. Concurrent with the falling enzyme levels, there was production
      of specific immunoglobulin G (IgG) antibody against iduronidase that was further
      associated with cellular infiltration of the myoblast injection sites. Most
      inflammatory cells were lymphocytes and plasma cells, suggesting local humoral
      and cellular immune responses to the enzyme-producing muscle cells. PCR analysis
      of tissues collected 2-22 weeks after the final treatment showed the persistence
      of Neo and canine alpha-L-iduronidase sequences in a progressively decreasing
      percentage of myoblasts. Results from this study in a canine model of
      mucopolysaccharidosis I underscore the fact that immunologic reactions to cells
      producing desirable, normal, but foreign, proteins may be as much an impediment
      to gene therapy as reactions to the viral vectors used to introduce the foreign
      gene.

PMID- 8864762
TI  - NIDDK Workshop on AAV Vectors: Gene Transfer into Quiescent Cells.

PMID- 8864761
TI  - Human fetal gene therapy: moral and ethical questions.
AB  - This two-part paper discusses moral and ethical questions raised by future trials
      of human fetal gene therapy. The first part examines broad moral issues to
      explore whether fetal gene therapy is a morally praiseworthy goal. Ought it be
      done at all? These issues include (i) how the concept of fetal gene therapy
      originally arose as a goal envisioned at the beginning of prenatal diagnosis,
      (ii) preimplantation genetic diagnosis as a better preconceptual alternative for
      parents at higher genetic risk, (iii) alternatives to genetic abortions, (iv) the
      social and economic priority of fetal gene therapy, and (v) whether fetal gene
      therapy is a "slippery slope" that will end in germ-line gene therapy. This part
      concludes that far more reasons exist to commend fetal gene therapy than to
      reject it, given its limits and modest social and economic priority. The second
      part responds to specific ethical questions that must be raised about any
      protocol for human gene therapy. These questions and issues are adapted to the
      prenatal situation: (i) how the previable fetus becomes a "patient," (ii) concern
      for clinical benefit and minimizing risks to the fetus and pregnant woman, (iii)
      concern for the voluntary and informed participation of the pregnant woman, the
      father, and for protection of their privacy, (iv) concern for fair selection of
      subjects, (v) considerations of harm to germ line cells, and (vi) the role of
      public oversight of fetal gene therapy. The article concludes by recommending a
      continuation of the consolidated Recombinant Advisory Committee (RAC) for the
      near future.

PMID- 8864763
TI  - Human gene marker/therapy clinical protocols.

PMID- 8864764
TI  - Alfred Bernhard Nobel (1833-1896)

PMID- 8864765
TI  - Physiology and function of platelets from patients with Alzheimer's disease.
AB  - The discovery that intact Alzheimer amyloid precursor protein is present in
      platelet granules, has created a great interest in the biochemistry, physiology
      and function of platelets of patients with Alzheimer disease (AD). In this study
      we monitored various biochemical and physiological parameters, such as serotonin
      and adenine nucleotide levels, membrane fluidity, agonist-mediated release of
      arachidonic acid, thromboxane formation, calcium mobilization, as well as
      irreversible aggregation and secretion of granule contents. Platelets of patients
      with AD responded poorly when stirred with weak or potent agonists on a platelet
      aggregometer. Although capable of agonist-mediated calcium mobilization and
      synthesis of thromboxanes, the aggregation response of platelets of patients with
      AD to thrombin and archidonate was considerably compromised. In view of the
      normal biochemistry and signal transduction capabilities, the compromised
      response of these cells to potent agonists like thrombin suggested an extrinsic
      defect. The present study has shown that a plasmatic factor is at least in part
      responsible for the functional abnormalities of AD platelets.

PMID- 8864767
TI  - Response of the portal vein of spontaneous hypertensive rats to intracellular pH.
AB  - The effect of intracellular pH perturbations on the portal vein preparations of
      spontaneously hypertensive rats and their control Wistar Kyoto rats was
      investigated. Intracellular alkalinity induced by application of 20 mM NH4Cl or
      20 mM trimethylamine produced dilatation of both preparations. Intracellular
      acidity induced by washout of the previous ammonium and trimethylamine solutions
      or by application of 20 mM sodium propionate solution caused constriction of both
      preparations. These responses of the portal veins of both animals to
      intracellular pH variations were qualitatively the same in nonactivated
      preparations and in preparations precontracted with 26 mM K+ or 1 microM
      norepinephrine. Recovery from acidic constrictions induced by washout of ammonium
      and trimethylamine solutions was significantly slower in spontaneous hypertensive
      rats than in Wistar Kyoto rats preparations. Conceivably, a lower intracellular
      pH in the vascular smooth muscle of the resistance vessels of hypertensive
      patients, as compared to normotensive individuals, may partly account for the
      hypertensive phenomena.

PMID- 8864766
TI  - Dose-response functions of apomorphine, SKF 38393, LY 171555, haloperidol and
      clonidine on the self-stimulation evoked from lateral hypothalamus and ventral
      tegmentum.
AB  - The experimental animals were implanted with two bipolar electodes, one in the
      lateral hypothalamus including medial forebrain bundle (LH-MFB) and other in
      ipsilateral ventral tegmental area-substantia nigra (VTA-SN) and were trained to
      press a pedal for self-stimulation. This provided the scope to compare directly
      the effect of a given dose of a drug on the two reward regions in the same animal
      in the same testing situation. The current intensity was set to produce
      intracranial self-stimulation (ICSS) response rates of 50% less than the maximal
      shaping response rates for the respective animals (M60). Following systemic
      (intraperitoneal) administration of apomorphine (a dopamine receptor D1/D2 mixed
      agonist), SKF 38393 (D1 > D3 > D2 agonist), LY 17155 or quinpirole (D3 > D2 and
      D1) agonist), haloperidol (a DA-D2 antagonist), and clonidine (noradrenaline
      receptor alpha 2 agonist), the ICSS response rates evoked from LH-MFB and VTA-SN
      were compared with vehicle or saline-treated animals on the basis of dose
      response functions. A dose-dependent inhibitory effect at M50 was observed with
      apomorphine (0.01-1.00 mg/kg) and haloperidol (0.05-0.30 mg/kg) for both the
      sites of stimulation. These doses of haloperidol did not produce any motor
      deficits like catalepsy and muscular rigidity. The dose-response and time-effect
      functions of SKF 38393 and LY 171555 at M50 showed the facilitation and
      suppression of ICSS of VTA-SN and LH-MFB respectively. Clonidine (0.05-0.25
      mg/kg) also produced inhibitory effect on ICSS rates, but this suppression was of
      different magnitude with respect to the site of stimulation. These doses of
      clonidine were in the range that did not prevent active pedal pressing responses.
      ED50 (the dose required to reduce the ICSS response rate 50% of the rate after
      administration of vehicle) for LY 171555 was 0.8 and 4.4 mg/kg for the ICSS of
      VTA-SN and LH-MFB respectively and thus statistically different ED50 for
      apomorphine was 0.27 and 0.36 mg/kg; and for haloperidol was 0.75 and 0.90 mg/kg
      for LH-MFB and VTA-SN respectively and thus not different significantly. ED50 for
      clonidine was 0.25 and 0.08 mg/kg for VTA-SN and LH-MFB respectively and thus
      statistically different. The two-way analysis of variance (ANOVAR) of interaction
      of dose-response function of alpha 2 agonist with respect to LH-MFB and VTA-SN
      showed significant independence in their suppressive effects.

PMID- 8864768
TI  - Brainstem auditory evoked potentials in epileptics on different anti-epileptic
      drugs.
AB  - The effects of anti-epileptic drugs (AEDs) on brainstem auditory evoked
      potentials (BAEPs) were studied on 32 female patients of epilepsy and 10 age
      matched normal healthy females (NS). The patients were divided into 6 groups,
      those not receiving medication (drug free, DF) and those receiving AEDs:
      Phenytoin (PHT), Carbamazepine (CBZ), Phenobarbital (PB), a combination of PHT
      and PB and a combination of CBZ and PB. DF epileptics had shortened were V
      absolute latency (AL) and I-V interpeak latency (IPL) as compared to NS.
      Phenytoin and CBZ monotherapy produced a prolongation of wave III AL (by PHT
      only), wave V AL, wave I-III IPL and I-V IPL, as compared to DF epileptics.
      Phenytoin monotherapy also prolonged wave III AL and I-III IPL, as compared to
      NS. When PB in the dosage of 30-60 mg/d was used in combination with PHT the
      above mentioned changes were not observed. These findings indicate altered
      neuronal conduction and/or synaptic transmission in epileptics. Anti-epileptic
      drugs in the dosages studied, with exception of PHT appear to lead towards
      "normalization" of BAEPs.

PMID- 8864769
TI  - Effect of noise stress on some cardiovascular parameters and audiovisual reaction
      time.
AB  - A study of the effect of noise stress on some of the physiological parameters was
      carried out on healthy male workers of thermal power station (exposed to sound
      level 90-113 dBA) and compared with age and sex matched healthy controls (exposed
      to sound level 48-66 dBA). The parameters recorded were heart rate (HR), systolic
      blood pressure (SBP), diastolic blood pressure (DBP), galvanic skin resistance
      (GSR), auditory and visual reaction time (ART and VRT) and audiogram. Significant
      impairment in audiogram at 3000 Hz and 4000 Hz, increase in HR, SBP, DBP and
      decrease in GSR, ART and VRT were recorded in workers who were exposed to noise
      stress. Also a higher prevalence of hypertension was observed in them and that
      they were at a higher risk of developing hypertension than the control group. It
      was also observed that these modifications are related to duration of exposure to
      noise stress. It is presumed that all the above extra auditory effects are due to
      activation of autonomic nervous system and hypothalamo-hypophyseal adrenal axis,
      and the resultant release of catecholamines from adrenal medulla due to noise
      stress.

PMID- 8864770
TI  - Central noradrenergic and cholinergic modulation of formaldehyde-induced pedal
      inflammation and nociception in rats.
AB  - Possible central noradrenergic and cholinergic modulation of acute peripheral
      inflammation was investigated in rats, adopting the formaldehyde-induced pedal
      inflammation as the experimental model. Intracerebroventricularly (icv)
      administered noradrenaline (NA), alpha-adrenoceptor agonist, L-phenylephrine,
      alpha-2 adrenoceptor agonist, clonidine and non-selective beta-adrenoceptor
      blocker, propranolol, suppressed formaldehyde-induced inflammation producing a
      decrease in oedema volume and increase in pain threshold. Conversely, both
      noradrenergic neuron degenerator, 6-hydroxydopamine (6-OHDA) and non-selective
      alpha-adrenoceptor antagonist, phenoxybenzamine produced an increase in paw
      oedema along with an augmentation of pain. Significant oedema augmenting effects
      were also produced by central excitatory neurotransmitter, acetylcholine (ACh) on
      icv administration. ACh also produced pro-nociceptive action. An ACh antagonist,
      scopolamine and ACh synthesis inhibitor, hemicholinium-3 (HC) reduced pedal
      oedema and produced analgesia. The results of this study indicate that central NA
      exerts an inhibitory effect on peripheral oedema and pain whereas, ACh has an
      augmenting effect on formaldehyde-induced peripheral inflammation.

PMID- 8864771
TI  - Chronic exercise alters EEG power spectra in an animal model of depression.
AB  - The EEG from frontal cortex, EMG and EOG were recorded from rats exposed to only
      exercise (Treadmill), only stress, exercise + stress and neither (control). In
      comparison with the control group, the percent of Delta activity in the awake was
      significantly increased in the depressed group and significantly decreased in the
      exercised groups, while for Beta-2, the reverse occurred; Theta increased and
      Beta-2 decreased in the NREM sleep state of the depressed group and the opposite
      happened for the exercised groups. Delta and Alpha-2 activity significantly
      increased in the depressed group, and they were significantly decreased in the
      exercised groups whereas the Beta-2 activity showed contrary changes in the REM
      sleep state. These findings indicate that exercise has the opposite effect from
      what stress has on qEEG and concomitant physical exercise reduces the effects of
      stress. Behavioral tests were done by Open Field (OF) and High Plus Maze (HPM).
      Slow EEG activity (Delta, Theta, Alpha) was significantly positively correlated
      with immobilization in the OF and defecation in both OF and HPM and negatively
      with the food intake, transfer latency in HPM; rearing, grooming and total
      ambulation in OF Whereas, fast activity (Beta-2) was significantly negatively
      correlated with immobilization in OF and defecation in OF and HPM, while
      positively with ambulation in the central squares of OF and time spent at the
      central cross and number of times arms crossed in the HPM.

PMID- 8864772
TI  - Svara (nostril dominance) and bilateral volar GSR.
AB  - The Svara yoga concept of Ida, Pingala and Susumna svara representing rest,
      active and turbulent states was examined in this study by recording nostril
      dominance (svara) and bilateral volar GSR (galvanic skin resistance) as an
      indicator of sympathetic activity under field and laboratory conditions. The
      sympathetic activity was low in Ida svara, followed by Pingala svara and was
      maximum in Susumna svara group of subjects under both field and laboratory
      conditions which agreed with the traditional Svara yoga description. The volar
      GSR on the right side more readily varied with svara, particularly so in the
      physically relaxed subjects of laboratory condition than the left volar GSR. The
      latter observation was worth noting because the subjects were right handed. The
      right side could be recommended as the standard site for recording volar GSR to
      closely reflect the sympathetic activity, particularly so when physical rest was
      given to subjects.

PMID- 8864773
TI  - Investigation into the possible mechanisms involved in altered digoxin levels in
      diabetic patients.
AB  - The present study was undertaken to investigate the possible factors which may
      contribute to the altered digoxin levels in diabetic patients. The digoxin levels
      were found to be significantly higher in diabetics (1.74 +/- 0.09 ng/ml) as
      compared to non-diabetics (0.76 +/- 0.07 ng /ml). There was a positive
      correlation between digoxin levels and glycosylated haemoglobin levels. All
      diabetic patients had serum creatinine, urea and potassium levels within normal
      limits. However, serum TSH levels were found to be significantly higher in
      diabetics as compared to controls. Serum tri-iodo-1-thyronine (T3) levels were
      found to be lower in diabetics as compared to non-diabetics. Our data suggests
      that diabetes-mellitus causes alteration of digoxin levels. One of the causes of
      this increase in digoxin levels may be a tendency towards mild hypothyroidism
      associated with diabetes mellitus.

PMID- 8864774
TI  - Regional specificity seen within hypothalamus in neuroimmunomodulation.
AB  - Wistar strain male albino rats lesioned and sham lesioned at Ventromedial
      hypothalamus (VMH) were used to study the neuroimmunomodulation by this brain
      region. Except the decrease in thymus weight/body weight ratio (P < 0.01), and
      its cellularity (P < 0.02) in immunized VMH lesion animals, the rest of the
      parameters like plaque forming cells (PFC), antibody titre, leukocyte migration
      inhibition index, foot pad thickness in the lesioned as well as the lesion
      immunized animals never deviated from their respective sham and immunized sham
      animals. Sham operated belongs to VMH when compared to control rats, showed
      marked decrease in spleen weight (P < 0.001), thymus weight (P < 0.02) and
      decrease in popliteal lymph node weight (P < 0.001) ratios. After immunization,
      the immunized sham animals showed a marked decrease in antibody titre (P < 0.05),
      PFC (P < 0.05), spleen (P < 0.05) and thymus (P < 0.001) weight ratios with the
      significant increase in splenic cell count (P < 0.01) compared to immunized
      control rats. VMH may be one of the information receiving center. However, from
      these results, it is inferred that VMH could not be a modulating center for the
      many of the parameters studied as far as neuroimmunomodulation is concerned.

PMID- 8864775
TI  - Effects of some psychotropic agents on cognitive functions in rats.
AB  - The effects of some psychotropic agents were evaluated on cognitive function in
      rats. Acute administration of antipsychotic agents chlorpromazine, haloperidol or
      pimozide-all inhibited the active avoidance response as elicited by pole climbing
      test-the least effect being seen with pimozide. The antianxiety benzodiazepines,
      lorazepam and alprazolam, also attenuated active avoidance learning with the
      latter showing lesser effects. Maze task performance was differentially affected
      by these psychotropic drugs with maze traversing time being increased
      significantly after all drug treatment, except alprazolam.

PMID- 8864776
TI  - Cardio respiratory changes associated with graded exercise and determination of
      aerobic power in male medical students (18-19 years).
AB  - The data from the study reveals the normal cardiopulmonary responses in untrained
      subjects (18-19 yrs) and their aerobic power. Fifty male medical students in the
      given age group were selected for the study. They were subjected to moderate,
      predetermined, graded exercise on a bicycle ergograph and parameters like heart
      rate, blood pressure and respiratory rate were recorded at rest, just after
      exercise and during recovery. VO2 max or aerobic power was calculated from
      Astrand's nomogram after determining work rate. Heart-rate, systolic blood
      pressure, double-product and respiratory rate rose linearly with increasing
      grades of exercise, while diastolic blood pressure recorded a fall. Aerobic power
      was found to be 2.10 litres/min in 18 years age group and 2.07 litres/min in 19
      years category. The determination of aerobic power or VO2 max gives an idea of
      the capacity and regulation of O2 transporting system and also sets a norm in
      assessing physical fitness.

PMID- 8864777
TI  - Effects of enalapril on lipid profile in diabetic and non-diabetic essential
      hypertensive patients.
AB  - Effectiveness of enalapril was studied in hypertensive patients with or without
      diabetes-mellitus. All the patients received enalapril, 5-20 mg per day for 9
      months. Enalapril effectively controlled the blood pressure and favourably
      altered the lipid levels and did not affect the glucose level in diabetics as
      well as non-diabetics. Enalapril may be considered as a better therapeutic option
      for the treatment of hypertension associated with diabetes mellitus.

PMID- 8864778
TI  - Effect of nitrendipine, nimodipine and nisoldipine on water and electrolytes
      excretion in rats.
AB  - In water loaded (5 ml/100 g) unanesthetized rats. nitrendipine (NT), nimodipine
      (NM) and nisoldipine (NS) (5 mg/ kg, i.p.) caused significant (P < 0.01) increase
      in water and Na+ excretion. However, there was no significant increase in K+
      excretion after NT, NM and NS administration. NS was more potent in increasing
      excretion of water load as compared to NT and NM. The glomerular filtration rate
      as assessed by creatinine clearance, was significantly (P < 0.01) increased in
      NT, NM and NS (5 mg/kg, i.p.) treated groups as compared to control. The mean
      creatinine clearance values after NT, NM and NS were 26.95 +/- 0.35, 22.11 +/-
      0.72 and 28.13 +/- 0.95 respectively as compared to 22.19 +/- 0.51, 18.77 +/-
      0.42 and 22.97 +/- 0.60 in corresponding control groups. The results of the study
      suggest that in addition to other effects, NT, NM and NS have a selective
      inhibitory effect on Na+ handling mechanisms in the nephron.

PMID- 8864779
TI  - A study of peripheral nerve function in neonates and infants.
AB  - Motor and sensory nerve conduction velocity, H-reflex and F-response have been
      studied in the age group showing maximum changes i.e. neonates and infants. The
      nerve conduction velocity in upper and lower limbs was 25 M/S and 23.75 M/S
      respectively in neonate age group; 34.4 M/S and 32.4 M/S respectively in infant
      group. A significant relationship of age with nerve conduction parameters
      (velocity, terminal latency) has been observed in infants group but not so in
      neonate group. H-reflex (late response) was elicited in both Abductor Pollicis
      Brevis and Soleus. It was present in small muscles of hand (i.e. APB) in all the
      neonates and 55% of the infants only. This could be attributed to immaturity of
      nervous system. However, in the lower limb, H-reflex could be elicited in 100% of
      infants and neonates. In the present study, the relationship of age and height
      with different nerve conduction parameters as well as H-reflex (latency) has been
      highlighted.

PMID- 8864780
TI  - GABAergic agents modify imipramine analgesia.
AB  - The influence of GABA agonists and antagonists on analgesic activity of
      imipramine (IMA, 20 mg/kg, ip) was studied using the hotplate method.
      Administration of GABAA receptor agonist muscimol (1 mg/kg, ip), GABAB receptor
      agonist baclofen (3 mg/kg, ip) or GABA-T inhibitor aminooxyacetic acid (25 mg/kg,
      ip) increased the analgesic effect of IMA. On the other hand pretreatment of
      GABAA receptor antagonist bicucukline (2 mg/kg ip), GABAB receptor antagonist
      delta-amino-n-valeric acid (50 mg/kg, ip) or GABA synthesis inhibitor
      thiosemicarbazide (50 mg/kg, ip) attenuated the IMA analgesia. These results
      suggest that the analgesic action of IMA may be mediated by functional alteration
      of a central GABAergic mechanism and/or subsequent stimulation of GABA receptors.

PMID- 8864781
TI  - Respiratory effects of occupational exposure to asbestos.
AB  - Ventilatory capacities of 73 Libyan men working in the Asbestos-Cement Pipe
      factory in Jenzur, a residential area near Tripoli, Libya and those of 73 age
      matched healthy Libyan men unexposed to asbestos were determined. The mean values
      of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)
      for men unexposed to asbestos were 3.89 +/- 0.084 and 3.64 +/- 0.082 liters
      respectively. The respective values for men exposed to asbestos were 3.62 +/-
      0.082 and 3.29 +/- 0.097 liters. Thus, there has been a significant decrease in
      the ventilatory function of the men exposed to asbestos as compared with age
      matched unexposed counterparts.

PMID- 8864782
TI  - Analgesic efficacy of two derivatives of O-hydroxy-naphthoquinone.

PMID- 8864783
TI  - Renal lipids in cyproheptadine treated albino rats.

PMID- 8864784
TI  - Left ventricular regression equations from single plane cine and digital X-ray
      ventriculograms revisited.
AB  - For the assessment of left ventricular volume from X-ray ventriculograms, widely
      known regression equations are used to correct for the irregular shape of the
      left ventricular lumen and the presence of the papillary muscles and
      trabeculations. These regression equations were derived in the late nineteen
      sixties and seventies. With all the changes in X-ray technology that have taken
      place over the past 20-30 years, the question was raised whether these regression
      equations were still valid. Therefore, 23 left ventricular casts of known volume
      were imaged in RAO20, RAO30 and RAO40 angiographic views and recorded on 35 mm
      cinefilm as well as in digital format. All the frames were traced manually by two
      observers and the volumes calculated by the Area Length and Simpson Rule
      approaches. The following conclusions could be drawn: inter- and intra-observer
      variations were small (systematic differences < 1.5 ml; random differences < 2.9
      ml) and statistically not significant; the regression equations are virtually the
      same for the RAO20, RAO30 and RAO40 views under the different circumstances; the
      Area Length method was associated with slightly smaller values for the standard
      error-of-the-estimate (SEE) suggesting a slight preference for this approach
      versus the Simpson Rule; significant differences were found between the cinefilm
      and digital regression equations; and the following new regression equations are
      proposed, which indeed differ significantly from the earliest proposals and less
      from the monoplane formulas proposed by Kennedy & Lange in the 1970s: [table: see
      text]

PMID- 8864785
TI  - Imaging of recurrent ventricular septal defect and supravalvular pulmonary
      stenosis eight years after assumed total surgical repair of tetralogy of Fallot.
AB  - A 42-year-old man underwent assumed total surgical repair of an acyanotic
      tetralogy of Fallot: a perimembranous ventricular septal defect (VSD) was closed
      with a dacron patch and myectomy of the infundibulum of the right ventricular
      outflow tract was performed. Reexamination eight years later revealed a large
      recurrent VSD and by surprise a narrow supravalvular ridge above rudimentary
      pulmonary cusps in the pulmonary trunk, leading to a pressure drop of 70 mmHg
      across the supravalvular stenosis. The latter finding was not recognized during
      the operation eight years before. The diagnosis could noninvasively be
      established by means of magnetic resonance imaging. During revision surgery the
      VSD was closed and an aortic homograft was inserted as conduit between the right
      ventricle and the pulmonary artery.

PMID- 8864786
TI  - MRI misinterpretation of spontaneous echo-contrast as a large left atrial
      thrombus.
AB  - A magnetic resonance imaging of the heart was obtained in a patient with history
      of mitral valve replacement, in whom cor triatriatum dexter was suspected. Dense
      left atrial echo-contrast, visualized during a previous transesophageal
      echocardiography, was incorrectly interpreted as a large thrombus extending into
      the pulmonary veins and the patient was referred for cardiac surgical evaluation.

PMID- 8864787
TI  - Regional myocardial shape alterations in patients with anterior myocardial
      infarction.
AB  - OBJECTIVE: To assess the impact of regional left ventricular curvature in
      patients with an acute anterior myocardial infarction on ventricular volume.
      METHODS: Left ventricular curvature was calculated at 100 points from apical four
      chamber echocardiograms of 68 patients with an acute anterior wall infarction.
      Curvature at any point of the contour was defined as the reciprocal of the radius
      of the circle that intersects that point tangentially and was independent of
      volume and geometric assumptions. Curvature, volume and shape of the patient
      group was compared with these measurements in 20 normal volunteers. RESULTS:
      Diastolic curvature differed at the borderzone of the infarct and the apical
      area. In the basal septal area (point 9-18) mean curvature was lower in the
      patient group (0.1 +/- 2.7 versus 2.1 +/- 0.7; p < 0.0001) as compared to the
      normal individuals. In the mid-septal area (point 22 to 27), mean curvature was
      more concave (-0.1 +/- 2.6) in the patient group corresponding to in the normal
      population (-0.4 +/- 1.3) p < 0.005. In the apex point 52 and 53 diverged with a
      curvature of 9.9 +/- 1.9 in patients versus 9.4 +/- 2.9 p < 0.005 in normal
      individuals. Systolic curvature diverged at the basal septum (point 1-4) with a
      mean curvature of 1.4 +/- 1.1 in patients compared to 3.5 +/- 2.5 in normal
      individuals p < 0.01. Curvature differed also in the mid-septal region (point 9
      29) with a curvature of -1.7 +/- 1.2 in patients versus 0.4 +/- 0.9 (p < 0.01) in
      normal individuals and in the apical septum (point 48-52) with a curvature of
      16.6 +/- 5.2 in patients and 13.9 +/- 2.6 (p < 0.0001) in healthy individuals
      Separation of patients with the greatest curvature alteration to those with minor
      curvature change revealed, that baseline curvature analysis can discriminate
      patients at risk for left ventricular remodelling. CONCLUSION: Regional curvature
      analysis correctly identifies the geometric changes induced by myocardial
      infarction. Apical systolic curvature can distinguish those patients that are at
      risk for left ventricular remodelling from those who are not at risk.

PMID- 8864788
TI  - Dobutamine stress echocardiography early after myocardial infarction treated with
      thrombolysis. Identification of myocardial viability and ischemia and relation to
      spontaneous functional recovery.
AB  - The aim of the study was to assess the ability of dobutamine stress
      echocardiography to detect myocardial viability and ischemia in patients with
      acute myocardial infarction treated with thrombolysis and to correlate the acute
      response to dobutamine with late spontaneous functional recovery at follow-up.
      Forty-two consecutive patients with myocardial infarction treated with
      thrombolysis underwent low- (5 and 10 mcg/kg/min) and high-dose (20 to 40
      mcg/kg/min) dobutamine stress echocardiography at a mean of 7 +/- 3 days of the
      acute phase. A follow-up 2D-echocardiogram was performed in all patients to
      evaluate the spontaneous recovery of function in the infarct area. On the basis
      of the response to the test, 3 groups of patients were identified: group 1
      included 7 patients showing an improvement in left ventricular asynergy score
      index at low doses (from 1.5 +/- 0.3 to 1.3 +/- 0.2, p < 0.05) with no
      deterioration at high doses, indicative of myocardial viability without ischemia;
      group 2 (23 patients) showed a significant improvement in the asynergy index at
      low doses (from 1.58 +/- 0.3 to 1.32 +/- 0.32, p < 0.05) followed by a
      deterioration at high doses (1.68 +/- 0.4, p < 0.05 vs low-dose), suggestive of
      residual myocardial ischemia in the infarct zone; group 3 included 12 patients
      who showed no significant changes in the baseline asynergy score index (1.67 +/-
      0.2) either at low or at high doses. The acute response to dobutamine stress
      echocardiography accurately predicted the spontaneous recovery of function in the
      infarct area at follow-up: both group 1 and group 2 patients showed a significant
      reduction in the asynergy score index (group 1: 1.16 +/- 0.3 vs 1.5 +/- 0.2, p <
      0.001; group 2: 1.43 +/- 0.3 vs 1.58 +/- 0.3, p < 0.05), while group 3 had no
      recovery in the asynergy index (1.67 +/- 0.2 vs 1.67 +/- 0.2). Thus, in patients
      with acute myocardial infarction treated with thrombolysis dobutamine stress
      echocardiography can detect myocardial viability in 71% and ischemia in the
      infarct zone in 55% of patients; moreover, the response to the test during the
      acute phase is correlated with the degree of the late spontaneous recovery of
      function in the infarct area.

PMID- 8864789
TI  - Ambulatory follow-up of aortic dissection: comparison between computed tomography
      and biplane transesophageal echocardiography.
AB  - Aim of the study was to assess the relative usefulness of transesophageal
      echocardiography (TEE) and X-ray computed tomography (CT) in the follow-up of
      patients who survived an aortic dissection. MATERIALS AND METHODS: We evaluated
      44 patients (age = 57 +/- 12 years) with treated aortic dissection: 14 had a De
      Bakey type I, 20 a type II and 1 patient a type III dissection treated
      surgically: 1 patient had a type I, 1 a type II and 7 a type III dissection
      treated medically. All entered an outpatient follow-up program with serial
      evaluations at 1, 6 and 12 months after initial diagnosis by dual noninvasive
      imaging protocol. A contrast-enhanced CT scan and a TEE with biplane probe were
      performed on the same day and in random order. RESULTS: A total of 252
      evaluations with both CT and TEE were considered. A completely normal study was
      found in 45 TEE and 48 CT evaluations. The following abnormal findings could be
      documented by one or both techniques: thrombus in the false lumen (TEE: n = 48;
      CT: n = 45 evaluations); intimal flap (TEE and CT: n = 68); aortic dilatation
      (TEE and CT: n = 15); pericardial effusion (TEE and CT: n = 3); aortic
      pseudoaneurysm (TEE: n = 2; CT: n = 3); isthmic coarctation (TEE and CT: n = 1).
      Regarding the presence or absence of these abnormalities, which are within the
      diagnostic domain of both imaging techniques, the results were fully concordant
      in 245 studies, and discordant in 7, with an overall agreement of 97%. In
      addition, some abnormal findings could be detected by TEE only: aortic
      insufficiency (n = 36); intimal tear (n = 25); spontaneous echocontrast effect in
      the false lumen (n = 39 evaluations). Other abnormal findings could be detected
      by CT only: a pleural effusion in 4, a truncus anonymous dissection in 1, a
      pseudoaneurysm due to suture dehiscence of the distal anastomosis of the
      ascending aorta in 1 evaluation (which yielded ambiguous results by TEE, with
      turbulent flow departing from the graft). CONCLUSION: Both CT and TEE are
      atraumatic, safe and accurate techniques for serial follow-up imaging of patients
      treated for aortic dissection. Information provided by CT is largely redundant,
      rather than additive, to that provided by TEE. The latter should be probably
      preferred for shorter imaging time, accuracy and convenience, although CT might
      still play a role in selected cases of ambiguous TEE results.

PMID- 8864791
TI  - Thallium-199: a new radiopharmaceutical for myocardial perfusion imaging.
AB  - The efficacy of a new radionuclide, thallium-199 for myocardial scintigraphy was
      compared with conventional thallium-201 imaging. Owing to the short half-life of
      thallium-199 (7.4 hours), when the injected dose of thallium-199 was increased to
      200 MBq, the total dose reaching the critical organs was 3.6-15.5 times lower
      than with conventional nuclide, thallium-201. Studies were performed in a total
      of 177 patients. The patients were divided into two groups(a) 17 patients with
      acute myocardial infarction and (b) 160 patients undergoing coronary angiography:
      55 patients with no significant coronary artery disease and 105 patients with
      coronary disease. The sensitivity of the test was 92% with a specificity of 82%
      and overall predictive accuracy of 84%. Myocardial images obtained with low and
      high energy collimators have similar predictive accuracy. Perfusion defects were
      detected more frequently with increasing severity of angina. Myocardial
      infarction was characterized by persistent defects and myocardial ischaemia by
      redistribution of thallium. Thallium-199 myocardial scintigraphy performed at
      rest can be used for the diagnosis of acute myocardial infarction and for the
      determination of infarct site and extent. Thallium-199 is a new myocardial
      imaging agent, with a predictive accuracy for the diagnosis of coronary artery
      disease similar to thallium-201, but a significantly reduced total body dose
      permits repeat studies with a reduced radiation dose for the patient.

PMID- 8864790
TI  - Feasibility of simultaneous Tc99m sestamibi and 2D-echo cardiac imaging during
      dobutamine pharmacologic stress. Preliminary results in a female population.
AB  - Feasibility of simultaneous 2D-Echo and SPECT Tc99m Sestamibi imaging during
      dobutamine infusion was evaluated in a female population with suspected coronary
      artery disease and scheduled for diagnostic coronary angiography. A total of 49
      consecutive subjects were studied. Patients under continuous ECG and 2D-Echo
      monitoring underwent standard dobutamine infusion at increasing doses to a
      diagnostic end-point. Tc99m Sestamibi was administered at the peak of the
      dobutamine effect. With this approach, 35 patients were identified correctly by
      2D-Echo (Sensitivity = 60.1%; Specificity = 83.3%; Agreement = 71.4%; k = 0.43).
      Perfusion imaging with Tc99m Sestamibi resulted in correctly identifying 41
      patients (Sensitivity = 83%; Specificity = 84%; Agreement = 83.6%; k = 0.67).
      Combining information obtained from the two tests resulted in increased
      specificity (92%) and decreased sensitivity (64%). Simultaneous assessment of
      perfusion and function with Tc99m Sestamibi and 2D-Echo imaging during dobutamine
      administration is easily performed without added risk or discomfort to the
      patient. Tc99m Sestamibi appeared to be slightly superior to 2D-Echo for the
      detection of CAD in this population, but the difference does not reach
      conventional statistical significance. The combined use of the two independent
      tests did not substantially improve the diagnostic accuracy of each method.

PMID- 8864792
TI  - Tc-99m tetrofosmin myocardial distribution 4 hours post injection.
AB  - The recommended protocol for Tc99m tetrofosmin myocardial imaging suggests either
      a one- or two day imaging protocol so that stress and rest studies are
      sufficiently separated in time to allow optimum myocardium to background uptake
      ratios to differentiate between myocardial ischaemia and/or infarction. The
      biokinetic data for tetrofosmin suggest that no significant changes occur in
      myocardial distribution up to 180 minutes post injection. It is, therefore,
      necessary for two doses of the radiopharmaceutical and two separate studies to
      evaluate the myocardial status during stress and rest. This study assessed the
      differences between the 1 and 4 hour post injection SPET images obtained
      following peak exercise in 20 consecutively chosen patients. In addition, these
      images were compared to the rest images obtained on the following day after a
      second dose of the radiopharmaceutical was administered. In 4 patients, a one and
      four hour post injection study was also done during the rest phase. The results
      demonstrate significant changes in Tc-99m tetrofosmin distribution between the
      one hour and four hour post injection images. These differences are present
      during the stress as well as rest studies.

PMID- 8864793
TI  - Differential systemic and pulmonary hemodynamic effects of L-arginine in patients
      with coronary artery disease or primary pulmonary hypertension.
AB  - The endothelial EDRF/NO-mediated relaxing mechanism is impaired in
      atherosclerotic and in hypertensive arteries. Recently, it was suggested that
      primary pulmonary hypertension might be another disease in which the endothelial
      EDRF/NO pathway is disturbed. We tested the hypothesis that intravenous
      administration of L-arginine (L-ARG), the physiological precursor of EDRF/NO,
      stimulates the production of NO, subsequently increasing plasma cGMP levels and
      reducing systemic and/or pulmonary blood pressure, in patients with coronary
      artery disease (CAD, n = 16) or with primary pulmonary hypertension (PPH, n = 5).
      L-ARG (30 g, 150 ml, 15 min) or placebo (150 ml NaCl) was infused in CAD
      patients, and L-ARG was infused in PPH patients during cardiac catheterization.
      Mean aortic (Pao) and pulmonary (PAPmean) arterial pressures were continuously
      monitored. Cardiac output (CO, by thermodilution), total peripheral resistance
      (TPR), and pulmonary vascular resistance (PVR) were measured before and during
      the infusions. In CAD patients Pao decreased from 87.2 +/- 4.9 to 81.8 +/- 5.1
      mmHg during L-ARG (p < 0.05), whereas PAPmean and PVR were unchanged. TPR
      decreased from 1008.9 +/- 87.9 to 845.0 +/- 81.7 dyne x sec x cm-5 during L-ARG
      administration (p < 0.01). CO significantly increased during L-ARG (from 7.3 +/-
      2.8 to 8.1 +/- 0.9 l/min, p < 0.05). Placebo did not significantly influence any
      of the hemodynamic parameters. Plasma cGMP (determined by RIA) slightly increased
      by 12.2 +/- 9.6% during L-ARG, but slightly decreased during placebo (-12.3 +/-
      9.2%) (p < 0.05 for L-ARG vs. placebo). In PPH patients, L-ARG induced no
      significant change in Pao, TPR, and CO, PAPmean was 59.4 +/- 8.5 mmHg at the
      beginning of the study and was not significantly reduced by L-ARG nor was PVR
      (basal: 1042.4 +/- 211.4 dyne x sec x cm-5) changed by L-ARG. Plasma cGMP was not
      significantly affected by L-ARG in these patients. We conclude that L-ARG
      stimulates NO production and induces vasorelaxation in CAD patients but not in
      patients with primary pulmonary hypertension.

PMID- 8864794
TI  - Zidovudine glucuronidation in human liver: interindividual variability.
AB  - Zidovudine 3'-azido-3'-deoxythymidine is the drug chosen for the treatment of
      patients suffering from AIDS; zidovudine being a potent inhibitor of HIV
      replication. The drug is extensively metabolized by conjugation with glucuronic
      acid into an inactive compound, and 30-40% of the dose is eliminated
      presystemically. We studied the variability and characterized the frequency
      distribution of the activity of zidovudine glucuronosyl transferase in 93
      specimens of human liver. A rapid and reproducible radiometric assay for the
      glucuronidation of 14C-zidovudine is reported. The method is based on the
      extraction of the unreacted zidovudine into organic solvents and the
      radioactivity of the unextractable zidovudine glucuronide was measured in the
      aqueous phase residue. The rate of zidovudine glucuronidation was neither sex-
      nor age-dependent, ranged over 1 order of magnitude, and was positively skewed.
      The possibility that endogenous bilirubin should interact with glucuronidation of
      zidovudine was explored and the endogenous concentration of bilirubin was
      measured in the microsomal preparations of 59 liver samples. The final
      concentration of bilirubin in the assay mixture for zidovudine glucuronidation
      ranged between 2.2 and 13.2 microM and did not interact with the rate of
      zidovudine glucuronidation. The kinetics of glucuronosyl transferase towards
      zidovudine was studied in 20 livers, Michaelis-Menten kinetics were observed and
      the K(m) estimate ranged over 2-fold with an average of 2.89 mM. These in vitro
      results are consistent with the view that the rate of glucuronidation varies over
      1 order of magnitude in the human liver and its distribution is positively
      skewed. This variability may modulate the patient's exposition to zidovudine and
      thereby the efficacy of therapy.

PMID- 8864795
TI  - In vitro and in vivo protein binding of methotrexate assessed by microdialysis.
AB  - The purpose of the study was firstly to estimate methotrexate protein binding
      using microdialysis, and secondly to determine the influence of the protein
      content in the dialyzed medium on the dialysis membrane recovery. In vitro
      recovery was estimated by both water recovery method and concentration difference
      method. The relative recovery was independent of methotrexate concentration:
      39.3% +/- 2.86% and 39.2 +/- 1.27% for 50 microM and 300 microM, respectively. A
      significant influence of the presence of proteins on the dialysis membrane
      recovery was observed: 55.9% +/- 2.7%, 42.3% +/- 7.5% and 45.5% +/- 0.1% for
      buffer, human serum albumin (HSA) (600 microM) and human plasma, respectively.
      Methotrexate binding to human and rat plasma proteins showed a nonsaturable
      phenomenon. The bound percentages and corresponding total binding capacities were
      58.7% +/- 3.13% and 1.44 +/- 0.033 mM-1 and 71.7% +/- 4.38% and 2.18 +/- 0.09 mM
      1 for the human and rat plasma, respectively. For HSA this binding was saturable
      with an affinity constant of 4.75 +/- 0.66 mM-1. After intravenous administration
      (250 mg/kg) the in vivo rat plasma binding of methotrexate was roughly 20% higher
      (93.6%) than the in vitro methotrexate plasma binding. The in vivo relative
      recovery of methotrexate was found to be 12.6% +/- 1.8% versus 25.4% +/- 3.3% in
      vitro. This study showed that the protein content can directly affect
      microdialysis probe recovery. However, by taking into account this recovery,
      microdialysis allows to measure the protein binding of methotrexate.

PMID- 8864796
TI  - Pharmacokinetics of tiaprofenic acid in infants after a single oral dose.
AB  - Ten healthy infants (15.2 +/- 10.6 months old, range 6-35) anesthetized for minor
      surgery were given a single oral dose (3 mg x kg-1) of tiaprofenic acid (TA).
      Seven venous blood samples and 0-12 h urine were collected. TA concentrations in
      plasma and urine were measured by HPLC. Within the whole group the mean +/- SD
      kinetic parameters were: Cmax: 10.55 +/- 3.31 mg x l-1, Tmax: 1.73 +/- 0.87 h,
      AUC0-1 32.53 +/- 4.42 mg x l-1 x h, AUC0-infinity 35.33 +/- 4.73 mg x l-1 x h,
      t1/2 1.82 +/- 0.48 h, Cl/F: 0.09 +/- 0.01 l x h-1 x kg-1, VZ/F: 0.23 +/- 0.08 l x
      kg-1. Renal clearance was 0.030 +/- 0.009 l x h-1 x kg-1. 32% of the TA dose was
      recovered in urine, 60% of which was conjugated. AUC0-8h increased significantly
      with age. The TA kinetic parameters were close to those in 3 to 11-year-old
      children. The present study suggests slight differences in the TA kinetics
      between infants and adults. However, the lack of an evidenced direct relationship
      between plasma TA concentration and either efficacy or tolerance suggests that
      the TA dose regimen in infants may not have to be different from that in adults.

PMID- 8864797
TI  - Comparative steady state study with 2 fenofibrate 250 mg slow release capsules.
      An example of bioequivalence assessment with a highly variable drug.
AB  - Twenty healthy male volunteers were treated with 2 different oral preparations of
      fenofibrate according to a randomized 2-way crossover design. The test
      preparation was Fenofibrate 250 mg retard capsules, batch No. YXF 001, provided
      by MTT Medical and Technological Transfer GmbH, Unterhaching, Germany. The
      reference preparation was Lipanthyl 250 mg retard capsules, batch No. R9110071,
      manufactured by Fournier Pharma, Sulzbach, Germany. On 12 consecutive days
      divided in 2 periods the volunteers received 6 doses of the test and reference
      formulation, respectively. The daily dose of 1 capsule contained 250 mg of
      fenofibrate and was administered together with a standardized high calory
      breakfast. Blood samples were taken immediately prior to each administration and
      at 14 points after the last administration of each period. The concentration of
      the pharmacologically active compound, fenofibric acid, was determined by means
      of HPLC with UV detection. The calibration curve was linear in the range 0.1-20.0
      micrograms/ml (r = 0.99997). A lower limit of quantification of 0.1 microgram/ml
      was established. The following mean values were obtained after administration of
      the test preparation: AUC tau 184.68 microgramsh/ml; Cmax 13.11 micrograms/ml;
      PTF: 125.0%. After administration of the reference formulation the following
      values were observed: AUC tau 175.91 microgramsh/ml, Cmax 12.27 micrograms/ml,
      PTF: 120.0%. AUC tau, Cmax and PTF were tested for bioequivalence parametrically
      after logarithmic transformation. The preparations were found to be
      bioequivalent.

PMID- 8864798
TI  - Pharmacokinetics of nitazoxanide after single oral dose administration in 6
      healthy volunteers.
AB  - The objective of this study was to gather first information on the time course of
      plasma concentrations and urinary excretion of the antiprotozoal nitazoxanide (N)
      and to identify potential metabolites in healthy subjects after a single oral
      dose of 500 mg of nitazoxanide. The clinical trial was conducted as an open
      single oral dose study in 6 healthy male subjects. After a standardized
      continental breakfast the subjects took a single oral dose of 500 mg nitazoxanide
      (coated tablet) with 100 ml tap water. The plasma concentration and the urinary
      excretion of nitazoxanide (N), desacetyl-nitazoxanide (DN), aminonitrothiazole
      (ANT), acetylsalicylate (AS), salicylate (S), gentisate (G) and salicylurate (SU)
      were monitored up to 72 h after administration. The only measurable species in
      plasma was DN, which reached a Cmax of 1.9 mg/l (range 1.1-2.5) 2-6 h after
      dosing, and an AUC of 3.9-11.3 mg x h/l. Its terminal half-life ranged from 1.03
      to 1.6 h. DN was extensively bound to plasma proteins (> 97.5%). Only 8% of the
      dose was recovered in the urine, in the form of DN (5%), SU (3%), and traces of
      ANT (0.1%). In vitro N was very rapidly hydrolyzed to DN by plasma esterases.

PMID- 8864799
TI  - The efficacy and potency of antiplatelet activity of ticlopidine is increased by
      aspirin.
AB  - Concomitant therapy with ticlopidine (T) and aspirin (ASA) profoundly increases
      spectrum of antiplatelet activities of both drugs. It was hypothesized that in
      addition to increased spectrum of activity (efficacy) each drug may potentiate
      the specific antiplatelet activity (potency) of the other. In 32 volunteers whole
      blood platelet aggregation (PA) in response to ADP, collagen, and arachidonic
      acid was evaluated ex vivo following 10-day treatments with normal or
      subthreshold doses of T or ASA with addition of second drug on the 5th day of
      administration of the first. PA was measured before, on day 5 and 10 of
      treatment. The results indicate that ASA increased spectrum of activity of T,
      i.e. T and ASA in combination, were significantly more effective against collagen
      induced PA than either drug alone. This increased efficacy was retained when
      subthreshold dose of T (100 mg, qd) was used. T was without effect on AA-induced
      and ASA on ADP-induced PA. However, ASA potentiated effect of T on ADP-induced
      PA; the subthreshold dose of T (100 mg, qd) in presence of ASA (100 mg, qd)
      exerted powerful inhibition. Thus, combination therapy increases both efficacy
      and potency of T allowing for reduction of the dose.

PMID- 8864800
TI  - Pharmacodynamics of ticlopidine: relation between dose and time of administration
      to platelet inhibition.
AB  - In spite of long clinical experience with ticlopidine (T) knowledge of its
      pharmacodynamics is limited. In this study relation between dose and time of
      administration of T to platelet inhibition was investigated in 62 healthy
      volunteers ex vivo in whole blood and platelet rich plasma. Gender-related
      sensitivity of platelets to ticlopidine was also evaluated. Inhibition of ADP
      induced platelet aggregation by T, 500 mg, daily, was almost identical in both
      sexes. 100 mg daily did not inhibit ADP-induced platelet aggregation even after
      14 days of administration. 250 mg daily induced strong inhibition on day 5 of
      administration comparable to the inhibition obtained with 500 mg daily dose. The
      antiplatelet (ADP) effect of T (500 mg, daily) was present on day 2-3 and full
      inhibitory effect on day 4 of administration. T1/2 of antiplatelet (ADP) activity
      of T was 5.3 days and full recovery of platelets activity 11-13 days. No rebound
      phenomenon was present. T (regardless the dose) inhibited platelet aggregation
      induced by small but not high concentrations of collagen and was without effect
      on arachidonic acid-induced platelet aggregation. Therefore, T is not suitable
      for treatment of acute event, 250 mg daily dose should be used especially for
      combination with other drugs and 11 days washout interval seems necessary to
      change the treatment or to perform surgery.

PMID- 8864801
TI  - Vitamin A supplementation in premature neonates with postnatal lung injury.
      Italian Collaborative Group on Preterm Delivery (ICGPD).
AB  - Vitamin A is widely used in neonatal intensive care units (NICU) to prevent and
      reduce lung injury in premature infants who require mechanical ventilation. As
      part of a project to assess the management in NICU, this study was designed to
      establish whether vitamin A supplementation in neonates at risk for
      bronchopulmonary dysplasia (BPD) increased and maintained their plasma levels to
      at least 20 micrograms/dl. Twenty-five preterm babies, 24-34 weeks gestation, 600
      1,770 g birth weight, received 1,000 IU/day of vitamin A intravenously for the
      first 28 days of life. At birth the majority had plasma vitamin A lower than 20
      micrograms/dl which rapidly rose during supplementation. Even though expected
      therapeutic plasma concentrations were reached in the majority of infants without
      exceeding the toxic level, no association was found between vitamin A plasma
      concentrations and maternal or newborns characteristics at delivery and clinical
      status or outcome of infants. Thus, even if dosage schedule may be furtherly
      optimized to reach and maintain wanted therapeutic ranges, the efficacy of
      routine therapeutic vitamin A supplementation has to be adequately proved.

PMID- 8864802
TI  - Salicylamide toxicity in overdose.

PMID- 8864803
TI  - Temporal bone and brain stem histopathological findings in Cornelia de Lange
      syndrome.
AB  - The temporal bone and the brain stem of an infant with Cornelia de Lange
      syndrome, aged 9 months, were studied histopathologically. Abnormalities in the
      inner ear included short cochlea, dilated vestibule, and mesenchyme-filled
      perilymphatic spaces of the vestibule and semicircular canals. The inner and
      outer hair cells were normal. Many spiral ganglion cells, which normally would be
      located in the canal of Rosenthal, were seen in the internal auditory meatus.
      Some of the vestibular ganglion cells intruded into the facial nerve. The facial
      nerve formed a loose curve and the geniculum was difficult to recognize. The
      middle ear was filled with mesenchyme, and there was marked dehiscence of the
      facial canal. The brain stem, particularly the pons, was smaller than normal,
      while the fourth ventricle was dilated. The microscopic observation of the pons
      revealed weak staining with Luxol Fast Blue and decreased number of
      oligodendroglia. These findings suggested the malformation of the myelin of
      transverse fibers.

PMID- 8864804
TI  - Bacterial attachment to oropharyngeal epithelial cells in breastfed newborns.
AB  - On day 2 post partum, swab samples were obtained from the oropharyngx of 20
      healthy, breast-fed babies. The samples were examined for aerobes (culture on
      agar plates), for bacterial coating with the immunoglobulins SIgA, IgG and IgM
      (immunofluorescence assay), for bacterial attachment to epithelial cells
      (fluorescence microscopy of acridine orange stained material, and scanning
      electron microscopy). alpha-Hemolytic streptococci grew almost exclusively in the
      oropharynx, while 32% (median value) of the epithelial cells showed bacterial
      attachment in abundance, viz. > 50 attached bacteria per cell, 66% (median value)
      of the bacteria showed positive reactivity when treated with anti-human SIgA
      serum. 72% (median value) of the bacteria were coated with IgG, but no IgM
      coating of the bacteria could be detected. Newborns do not possess IgA
      antibodies, as only IgG is able to pass the placental barrier. The SIgA-rich
      colostrum is capable of coating the oropharyngeal bacteria of breast-fed babies
      during their first days after birth. However, despite abundant SIgA-coating,
      bacteria still succeed in attaching to the epithelial cells of the oropharynx.
      This finding hints that factors other than SIgA impede the bacterial/cellular
      adhesion mechanism.

PMID- 8864805
TI  - Prevalence of otitis media in a survey of 591 unselected Greenlandic children.
AB  - In an unselected survey in two Greenlandic towns, 591 children were examined to
      study the prevalence of otitis media (OM). The attendance rate in Nuuk was 80%,
      while 93% participated in Sisimiut. The children were three-, four-, five- and
      eight-years-old and represented 18% of children in these age groups in all
      Greenland. In total, 51.7% in Nuuk and 54.1% in Sisimiut presented pathologic
      middle ear affections ranging from slight to severe. The prevalence rates of
      chronic OM (COM) were 6.8% in Nuuk and 11.7% in Sisimiut (P = 0.055) but without
      significant age or sex difference. The acute OM point prevalence rate was between
      1.5% and 0.4%. The prevalence rate of middle ear effusion (MEE) was between 23.0%
      and 28.2%. Secretory OM was significantly more prevalent in the younger age
      groups. The odds ratio of having COM was significantly higher in children with
      two Greenlandic born parents (3.07) than in children with only one Greenlandic
      born parent. A follow-up study after one year in Sisimiut revealed unchanged or
      aggravated middle ear disease in 56.8% of 82 children with middle ear pathology
      at the primary survey. Thus, OM persists as a major health problem among
      Greenlandic children, although the general socio-economic and medical conditions
      have improved during the last decades. Proposals are provided for increased
      otologic efforts.

PMID- 8864806
TI  - Auditory brainstem responses in infants and children with anoxic brain damage due
      to near-suffocation or near-drowning.
AB  - We studied auditory brainstem responses (ABRs) of sixteen infants and children
      with brain damage after anoxic accidents due to near-suffocation or near
      drowning. The patients manifested cerebral palsy, mental retardation and/or
      epilepsy and showed poor responses in the behavioral audiometry. Auditory
      brainstem responses were abnormal in five of the patients in the near-drowning
      group (waves I, II and III only were present in three patients and the amplitudes
      of waves IV and V were low in two patients) but normal in most of the patients in
      the near-suffocation group. This difference in the ABRs between the two groups
      suggest that in infants and children anoxic brain damage due to near-drowning
      might involve not only the cerebral cortex and subcortical white matter but also
      the upper brainstem and midbrain.

PMID- 8864807
TI  - Two cases of bilateral congenital cholesteatoma--usual and unusual presentations.
AB  - Bilateral congenital cholesteatomas are rare. We present the 8th and 9th case of
      this entity in the literature. One of these cases is especially unusual. In that
      patient an ear that had been documented as normal, both radiographically and
      clinically, was found to have a large cholesteatoma 18 months after the
      contralateral ear had been treated for the same disease. The theories of the
      pathogenesis of this entity are also reviewed. Our cases support several of these
      theories. In fact, in one of the patients, it is possible that a different
      etiology was involved in each ear. Incidental note is made of the fact that three
      of the nine reported cases of bilateral congenital cholesteatoma have occurred in
      the same geographic locale.

PMID- 8864808
TI  - Type III-IV laryngotracheoesophageal cleft: report of a successfully treated
      case.
AB  - This report presents a case of Stage III laryngotracheoesophageal cleft (LTEC).
      It is, to our knowledge, the fourth case in which the patient is still alive
      twenty months after surgery. We herein describe an initial symptomatology
      dominated by a bubbling hypersalivation, our surgical technique using a pleural
      shred of interposition and an endoscopic check during the operation and, finally,
      the clinical development dominated by a food intake refusal which was
      progressively improved through psychiatric help.

PMID- 8864809
TI  - The global burden of trachomatous visual impairment: I. Assessing prevalence.
AB  - This paper summarizes primary epidemiologic studies of trachomatous blindness to
      develop age-/sex-/region-specific estimates of the global prevalence of
      trachomatous blindness and low vision. These studies are first examined for their
      validity and then employed to derive a 'minimum' prevalence of trachomatous
      visual impairment. This method yield a global total for 1990 of approximately
      640,000 cases of trachomatous blindness, corresponding to a prevalence of
      0.12/1,000 (lower and upper bounds, 0.10 to 0.14/1,000). When those with low
      vision due to trachoma are included, 1.5 million cases of visual impairment are
      estimated, corresponding to a prevalence of 0.28/1,000 (lower and upper bounds,
      0.15 to 0.75/1,000). A second approach, labeled the 'projected' prevalence of
      trachomatous visual impairment, selects country-wide studies to derive
      representative regional prevalence values. A global total of 2,899,000 blind
      ("projected' prevalence of 0.55/1,000 with lower and upper bounds, 0.37 to
      0.83/1,000) is estimated for 1990. With trachomatous low vision included, greater
      than 6.7 million individuals in 1990 have visual impairment from trachoma
      ("projected' prevalence of 1.28/1,000 with lower and upper bounds, 0.53 to
      4.29/1,000). Analysis of the distribution of the global prevalence by age,
      gender, visual acuity and region provide direction for trachoma research and
      programme priorities. Attention is drawn to the limited studies and resulting
      wide variation in the estimates of trachomatous visual impairment prevalence as
      indicated by the lower and upper bound estimates. It is recommended that this
      epidemiologic uncertainty be reflected in global and regional estimates of
      trachomatous visual impairment prevalence in order to draw attention to how
      little is known and emphasize the need for further surveys. A second paper
      incorporates these findings in an assessment of the global burden of trachomatous
      visual impairment.

PMID- 8864810
TI  - The global burden of trachomatous visual impairment: II. Assessing burden.
AB  - This paper builds on results of a previous paper on the prevalence of
      trachomatous visual impairment as the foundation for assessing the global burden
      of trachomatous blindness and low vision: approximately 2.9 million cases of
      trachomatous blindness and 3.8 million low visioned corresponding to a global
      prevalence of trachomatous visual impairment equal to 1.3/1,000 in 1990 was
      estimated. For each visually impaired person, the years of life lost due to
      premature mortality and the years lived in a handicapped state are added to yield
      a single measure of disease burden called handicap adjusted life years (HALYs).
      Age, gender and visual acuity group specific HALYs are multiplied by the
      prevalence of trachomatous visual impairment to yield an estimate of the global
      burden of trachoma visual impairment equal to 80 million HALYs. Analysis of the
      distribution of the global burden by age, gender, visual acuity and region
      provide direction for trachoma research and programme priorities. Sensitivity
      analysis reveals that the burden estimates of trachomatous visual impairment may
      vary from as low as 15 million to as high as 500 million HALYs. Given this degree
      of variability, burden comparisons with other blinding and non-blinding
      conditions for the purposes of identifying health sector priorities may be
      misleading.

PMID- 8864811
TI  - Late complications in branch retinal vein occlusion.
AB  - Neovascularization in branch retinal vein occlusion usually develops 6-12 months
      after the onset of the disease, although some cases have been reported in which
      neovascularization and subsequent vitreous haemorrhage developed 2-3 years later.
      This is a report of nine cases of late appearance of vitreous haemorrhage due to
      branch retinal vein occlusion, which occurred 3-6 years after the initial onset
      of the disease. In two of these nine cases the vitreous haemorrhage was very
      profound and had to be managed by vitrectomy. We have studied the remaining seven
      cases, which had retinal ischaemia and optic disc or retinal neovascularization
      documented by fluorescein angiographic examination. Laser coagulation was applied
      in these seven cases, which resulted in considerable regression of the
      neovascularization and absorption of the vitreous haemorrhage. In one out of the
      seven cases recurrent vitreous haemorrhages appeared and it was finally treated
      by vitrectomy. Visual acuity improved in six of the seven cases. The follow-up
      period ranged from 12 to 48 months. The late appearance of the ischaemic type of
      branch retinal vein occlusion with neovascularization can be attributed to the
      change in character of the initially mild oedematous form of the disease. Partial
      posterior vitreous detachment and traction exerted at some later stage upon the
      neovascularization could be additional factors of the late appearance of vitreous
      haemorrhage. Patients with branch retinal vein occlusion should be followed up
      regularly over a long period of time in order to avoid late complications of the
      disease, such as vitreous haemorrhage following optic disc or retinal
      neovascularization.

PMID- 8864812
TI  - Pyogenic granuloma.
AB  - A retrospective review of cases of pyogenic granuloma seen at the King Khaled Eye
      Specialist Hospital, Riyadh, Saudi Arabia between 1984-1991 is described.
      Epidemiology and the factors that led to the granuloma formation were examined
      and only cases documented histopathologically were included in the review. Of the
      110 cases, 80% developed the granuloma at the site of the previous surgery
      (especially entropion repair, and dacryocystorhinostomy with a stent tube or with
      a Jones tube) while 20% did not have a prior surgery. Recurrence occurred in 7%
      and these patients were in the group who had a prior surgery. Surgical procedures
      lead to an increased tendency for the formation of pyogenic granuloma due to
      different mechanisms acting via a mechanical or chemical irritation and an
      inhibition of re-epithelialization.

PMID- 8864813
TI  - Ocular morbidity in patients with active systemic tuberculosis.
AB  - The ocular morbidity pattern in 2010 eyes of 1005 patients with active pulmonary
      and extrapulmonary tuberculosis was studied prospectively. A complete clinical
      (ocular and systemic) examination, radiologic evaluation, Mantoux test and sputum
      analysis for acid-fast bacilli were carried out in all patients. The ocular
      morbidity in patients in this study with active tuberculosis was 1.39%. The most
      common ocular finding was bilateral healed focal choroiditis (50%). No case of
      Eales' disease was found in this series. There was no statistically significant
      correlation between the ocular lesions and Mantoux positivity.

PMID- 8864814
TI  - Mycotic keratitis: susceptibility to antiseptic agents.
AB  - Oculomycosis is a severe problem in most developing countries. Specific
      antifungal agents are often unavailable, and are expensive. The use of antiseptic
      agents was therefore explored. Fungal isolates from patients in India and Ghana
      were tested against chlorhexidine, povidone iodine, propamidine, and
      polyhexamethylenebiguanide, and compared with econazole by placing the drugs in
      wells made in Sabouraud's agar plates seeded with the test organism. Fungal
      sensitivity testing is a contentious area but this method is simple and cheap.
      Chlorhexidine showed a good dose related response, povidone iodine showed a good
      response at all concentrations and econazole was the most effective in vitro. A
      small pilot study was conducted in India to assess clinical efficacy for fungal
      corneal ulcers. Both chlorhexidine and econazole proved effective but povidone
      iodine was ineffective. We suggest that chlorhexidine may be a useful first line
      agent for fungal keratitis when other antifungals are not available.

PMID- 8864815
TI  - Distribution of intercellular adhesion molecule-1 on leukocytes and corneal
      endothelium after endotoxin stimulation in rats.
AB  - After stimulation with Salmonella typhimurium endotoxin, the intercellular
      adhesion molecule-1 (ICAM-1) was studied on the corneal endothelium and
      associated leukocytes in rats using immunoscanning electron microscopy. Two
      hundred micrograms of the endotoxin was injected in Lewis rats. The corneae were
      excised at 0-h and 16-h-postinjection time (n = 5, respectively). The corneae
      were prepared in hypothermic University of Wisconsin (UW) solution for
      immunoscanning electron microscopy. Histotopographical examination visualized
      ICAM-1 antigen on cytoplasmic processes of the corneal endothelium, arranged
      along microfolds, especially at the peaks. In the leukocytes, ICAM-1 was located
      primarily in morphologically non-specialized domains of the cell body surface,
      and only rarely scattered on the surface of microvillar projections. We concluded
      that the endotoxin stimulation can increase ICAM-1 in both corneal endothelium
      and associated leukocytes. Increased ICAM-1 may be an important factor for the
      leukocytes to form clustering and adhering to the corneal endothelium.

PMID- 8864816
TI  - The ophthalmological course of Usher syndrome type III.
AB  - Usher syndrome is a recessive hereditary disease group with clinical and
      genetical heterogeneity leading to handicapped hearing and visual loss until
      middle age. It is the most common cause for deaf-blindness. Three distinct
      phenotypes and five distinct genotypes are already known. In Finland the
      distribution of known Usher types is different than elsewhere. Usher syndrome
      type III (USH3) is common in Finland and it is thought to include 40% of
      patients. Progressive hearing loss is characteristic of USH3. Elsewhere USH3 has
      been regarded as a rarity covering only several percent of the whole Usher
      population. The aim of this paper is to describe, for the first time, the course
      of visual handicap and typical refractive errors in USH3 and compare it with
      other USH types. From a total patient sample consisting of 229 Finnish USH
      patients, 200 patients' visual findings were analyzed in a multicenter
      retrospective follow-up study. The average progress rate during a 10-year follow
      up period in different USH types was similar. The essential progress occurred
      below the age of 40 and was continuous up to that age. Visual acuity dropped
      below 0.05 (severely impaired) at the age of 37 and the visual fields were of
      tubular shape without any peripheric islands at the average age of 30. Clinically
      significant hypermetropia with astigmatism seems to be a pathognomonic clinical
      sign of USH3.

PMID- 8864817
TI  - Corynebacterium minutissimum endophthalmitis: management with antibiotic
      irrigation of the capsular bag.
AB  - Chronic endophthalmitis, due to Corynebacterium minutissimum, developed in a
      patient following uncomplicated extracapsular cataract extraction and posterior
      chamber intraocular lens (PC-IOL) implantation. In this case, which to our
      knowledge is the first reported case of Corynebacterium minutissimum
      endophthalmitis, chronic inflammation persisted for 8 months with fluctuations in
      the inflammation. The specimens from the capsular bag yielded positive culture,
      but the vitreous culture was negative. The case was successfully treated by a
      capsular bag irrigation with vancomycin.

PMID- 8864819
TI  - Genetic contributions to SLE.

PMID- 8864818
TI  - Incomplete posterior U.G.H. syndrome--different iatrogenic entity?
AB  - U.G.H. syndrome is a known complication of IOL implantation associated with the
      use of anterior and rarely, posterior chamber intraocular lenses. It is due to
      mechanical excoriation of the angle or iris by the haptics or optic of an IOL and
      consists of uveitis, glaucoma and hyphema (U.G.H.). The advised therapeutic
      approach is explantation of the IOL. Following implantation of a posterior
      chamber IOL, three patients presented with bleeding into the posterior chamber,
      one associated with glaucoma. No patient had signs of uveitis. We decided to
      address the symptoms and not to explant the IOL. We believe that this constitutes
      a variant of the 'classical' U.G.H. syndrome, namely an incomplete posterior
      U.G.H. (I.P.U.G.H.) syndrome, in which explanation of the I.O.L. is not
      compulsory.

PMID- 8864820
TI  - Differences between normal and autoimmune T cell responses to autologous
      erythrocytes and haemoglobin: impairment of haptoglobin-mediated inhibition in
      NZB spleen cells.
AB  - Helper T cells are required for development of the autoantibody responses to
      native mouse erythrocytes (MRBC) that spontaneously develop in NZB mice. However,
      the stimulus for these Th is not known. Therefore, we compared the abilities of
      splenic T cells from actively autoimmune old NZB mice and preautoimmune, young
      NZB mice with those of T cells from nonautoimmune strains of mice to respond to
      autologous erythrocytes. We found that autologous RBC ghosts, washed free of
      haemoglobin, induced low, but statistically significant, proliferative responses
      in T cells from old NZB mice but not in T cells from young NZB or from normal
      young and old BALB/c mice. In addition, autologous RBC lysates induced
      proliferative responses detectable by 3H-thymidine uptake in T cells from
      nonautoimmune as well as autoimmune mice. CD4+ T cells accounted for most of the
      observed RBC lysate-induced proliferation, with virtually no response made by
      CD8+ T cells or B cells. T cells from actively autoimmune NZB mice were not more
      active in their responses to RBC lysates than T cells from normal strains of mice
      in terms of their level of proliferation, kinetics, or dose response. Haemoglobin
      was the major stimulus in the autologous RBC lysates and a similar stimulation
      was seen with lysates and haemoglobins from horse, human, and mouse sources.
      Haptoglobin, a haemoglobin-binding serum protein, inhibited T cell responses to
      haemoglobin and haemoglobin-containing RBC lysates but did not have the same
      effect on these responses in T cells from either young or old NZB mice.
      Therefore, either or both of the RBC stimuli from autologous RBC might account
      for the helper T cell activity in autoimmune NZB mice. T cells in normal mice do
      not respond either to RBC lysates in the presence of haptoglobin or to RBC
      ghosts.

PMID- 8864821
TI  - Dysregulated transforming growth factor-beta in neonatal and adult autoimmune MRL
      lpr mice.
AB  - Transforming growth factor- beta (TGF- beta) is a cytokine that promotes
      inflammatory processes and prevents tissue injury. Autoimmune destruction of the
      kidney in MRL-lpr mice is spontaneous, rapid, fatal and consists of glomerular
      damage and an influx of lymphocytes surrounding vessels and in the interstitium.
      In MRL-lpr mice, cytokine dysregulation is apparent in neonates and continues
      throughout the life span. Circulating levels of tumour necrosis factor (TNF-
      alpha) and colony stimulating factor-1 (CSF-1) are detected in neonatal mice and
      progressively increase in proportion to the loss of renal function. We now report
      elevated intracellular expression of distinct isoforms of TGF- beta (TGF- beta 3,
      TGF- beta 2, and TGF- beta 1) detected immunohistochemically in MRL-lpr kidneys
      and other tissues including the liver and thymus. Enhanced TGF- beta 3 and TGF-
      beta 2 isoforms are detectable in neonatal mice within the renal tubular
      epithelial cells (TEC) and vascular smooth muscle cells (VSMC). In MRL-lpr mice 4
      6 months of age, TGF- beta 2 and TGF- beta 1 are detected in TEC, VSMC,
      glomerular epithelial cells (GEC) and in perivascular infiltrating cells. By
      comparison, TGF- beta is minimally detectable in the normal kidneys of age and
      sex matched MRL(-)+2 or C3H/Fej mice. Paradoxically, in vitro cultured TEC and
      VSMC from MRL-lpr mice secrete less TGF- beta than TEC and VSMC isolated from
      MRL(-)+2 or C3H/FeJ mice. TNF- alpha, but not IL-6, CSF-1, or IFN- gamma
      stimulated the secretion of TGF- beta in TEC and VSMC. Our data demonstrate the
      dysregulation of TGF- beta isoforms in neonatal and adult MRL-lpr mice prior to
      and after the onset of autoimmune renal disease. We suggest that TNF- alpha
      and/or other molecules increase TGF- beta expression in MRL-lpr mice. We
      speculate that enhanced expression of TGF- beta promotes autoinmune renal injury
      in MRL-lpr mice.

PMID- 8864822
TI  - Silicone does not potentiate development of the scleroderma-like syndrome in
      tight skin (TSK/+) mice.
AB  - Several reports have implicated an association between the development of
      connective tissue disorders and exposure to silicone in breast implant patients.
      These connective tissue disorders include local or systemic scleroderma-like
      syndrome and have been characterized by fibrosis as well as the presence of
      circulating autoantibodies. Whether silicone does potentiate the development of a
      scleroderma-like syndrome is still to be defined. The purpose of the present
      study was to determine the effect of silicone on the tight skin (TSK/+) mouse
      which develops a scleroderma-like syndrome and on its normal pa/pa TSK/-
      littermate. Groups of six TSK and five of their normal pa/pa littermates were
      injected subcutaneously with low molecular weight silicone (LMW-PDMS), high
      molecular weight silicone gel (HMW-PDMS), incomplete Freunds' adjuvant (IFA) or
      Hank's balanced salt solution (HBSS) in the dorsal neck area and ventrally in the
      upper chest region. Serum was obtained prior to and 1 month after injection of
      silicone, IFA, or control HBSS. Antibody levels to bovine serum albumin (BSA),
      RNA polymerase (RNAP) and topoisomerase I were determined. Mice were then
      euthanized and strips of skin from the injection sites as well as samples of
      kidney and liver were studied histologically. No significant pathological changes
      were observed in TSK/- mice 1 month following injection with HBSS, LMW-PDMS or
      HMW-PDMS. Skin samples from TSK/+ mice which received LMW-PDMS showed hyperplasia
      of the dermis and peri-panniculus carnosus tissue and infiltrates of macrophages
      containing lipid-like vacuolated materials. Lipid vacuoles were observed
      throughout the deeper dermis as multiple loculated vacuoles. TSK mice which
      received HMW-PDMS showed similar thickening of the dermis and the peri-panniculus
      carnosus connective tissue. There were no significant differences in the
      histologic characteristics of the silicone-injected TSK/+ mice compared to those
      that received HBSS or IFA. No detectable changes in the kidney, spleen, or liver
      samples taken from TSK/+ or TSK/- mice injected with HBSS, IFA or silicone (LMW
      PDMS, HMW-PDMS) preparations were noted. Baseline circulating antibody levels to
      BSA, RNAP and topoisomerase were significantly higher in TSK/+ mice compared to
      the control TSK/- littermates. Administration of silicone (LMW-PDMS or HMW-PDMS)
      did not significantly alter circulating antibody levels to BSA, RNAP and
      topoisomerase in either the TSK/+ or the TSK/- mice. The results of this study
      indicate that silicone administration does not potentiate the development of the
      scleroderma-syndrome characterized by skin lesions and presence of circulating
      antibodies in the TSK/+ model.

PMID- 8864823
TI  - Autoantibodies against rat prostate antigens. Association of specific IGG2b and
      IGG2c with the DTH response.
AB  - Although autoimmune response against most tissues in the body has been
      extensively described, very little is known about autoimmune response against
      prostate antigens either in humans or animals. In this work we studied the
      autoimmune response elicited against rat prostate (RP) in Wistar rats immunized
      with a chemically modified extract of syngeneic male sex accessory glands (MRAG).
      We observed that one immunization was enough for the induction of positive
      delayed-type hypersensitivity test (DTH), which was higher on day 15 than on day
      30. It was also enough to induce IgG autoantibodies to RP although a second
      injection was necessary to obtain a more frequent occurrence and a greater
      reactivity. The autoantibodies against RP were directed mainly to the cytosolic
      fraction and reacted at least with two molecules of 43 and 20 KD. Sera obtained
      on days 30 and 45 showed presence of specific IgG, IgA and IgM. Specific IgG2b
      and IgG2c were found on both days. On day 30 none of the sera presented IgG2a
      anti-RP, while on day 45 only 38% of the sera were considered positive for this
      isotype. No IgG1 anti-RP was detected in any serum of either bleeding. Direct
      immunofluorescence staining showed intense immunofluorescence in prostate
      epithelium, mainly in the apical zone of the gland, in animals that had received
      two immunizations with MRAG-CFA. No positive staining was seen in prostates
      obtained on day 30 after just one immunization, in sections of normal prostates
      or in sections of other rat organs. Our data indicate that the main isotypes
      involved in this autoimmune phenomenon are IgG2b and IgG2c. A strong association
      between the cellular autoimmune response measured by the DTH response and the
      IgG2b and IgG2c isotype was found at early stages of the disease. Since the DTH
      response and the IgG2b isotype have been previously associated with Th1-like
      activity in rats, our results suggest that Th1-like cells could be playing an
      active role in early stages of this disease.

PMID- 8864824
TI  - Induction of diabetes in NOD<-->C57BL/6 embryo aggregation chimeras by
      cyclophosphamide through preferential depletion of C57BL/6 lymphocytes.
AB  - The majority of embryo aggregation (EA) mouse chimeras between non-obese diabetic
      (NOD) mice and C57BL/6 (B6) mice show clear signs of insulitis frequently
      accompanied by beta-cell destruction. Less than 5% of these chimeras, however,
      spontaneously progress to autoimmune diabetes, an incidence far lower than
      observed in NOD mice. The resistance in chimeras can be accounted for by the
      target organ chimerism and/or the immune system chimerism. To investigate the
      mechanism(s) controlling diabetes resistance in these mice, we studied a total of
      92 NOD<-->B6 EA chimeras that showed overt lymphoid chimerism and treated 34
      chimeras with cyclophosphamide (CY), a compound known to precipitate an acute
      form of insulin-dependent diabetes mellitus (IDDM) in pre-diabetic NOD mice, by
      interfering with regulatory mechanisms. We found that CY-treated EA chimeras
      displayed an increase in the NOD:B6 lymphocyte ratio and 32% of them developed
      diabetes that could be adoptively transferred to irradiated NOD or NOD-rag-2-/-
      mice. These findings suggest that lymphocyte chimerism rather than beta-cell
      chimerism accounts for diabetes resistance in NOD<-->B6 EA chimeras and that the
      susceptibility to CY-induced diabetes may be related to the proportion of NOD
      versus B6 lymphoid cells.

PMID- 8864825
TI  - Changes in B and T lymphocytes associated with mycobacteria-induced protection of
      NOD mice from diabetes.
AB  - Most female NOD mice spontaneously develop insulin-dependent diabetes mellitus
      (IDDM) after the 4th month of age. We have recently reported that infection of 2
      month-old NOD mice with Mycobacterium avium prevents IDDM expression in these
      mice. We have searched here for changes in splenic lymphocytes that are
      associated with the effect of M. avium vaccination. Three experimental groups of
      female NOD mice were studied: (i) animals infected with 10B viable M. avium
      bacteria (mice that become protected from IDDM); (ii) mice inoculated with 10B
      heat-killed (HK) M. avium bacilli, and (iii) untreated age-matched NOD mice.
      Similar treatments were given to mice of the NON strain which are related to NOD
      mice but do not develop IDDM. Flow cytometry was used to compare M. avium
      infected, HK M. avium inoculated and untreated NOD and NON mice with regard to
      subpopulations of splenic lymphocytes bearing the surface antigens CD3, CD4, CD8,
      IgM and B220. We found that M. avium infection of NOD mice caused a sustained
      enhancement in T cells that was due to an early and transient increase in CD8+ T
      cells (detected at day 7 of infection). This was followed by marked augmentation
      in the number of CD4+ T cells at days 14 and 30. There was also elevation in
      B220+ B cells at days 14 and 30, and of IgM+ B cells at day 30 of infection.
      Inoculation of NOD mice with HK mycobacteria, which did not prevent IDDM, failed
      to produce significant changes in the number of T and B cells. No significant
      enhancement in T and B cells was observed in NON mice that were injected with
      either viable or HK M. avium bacilli. In NOD mice that reached 16 months of age
      because of being protected from IDDM (due to the M. avium infection) there was an
      increase in B220+ B cells. We conclude that: (i) M. avium-induced protection of
      NOD mice from diabetes depends on the viability of the bacteria; (ii) the
      protective effect of the infection is associated with an early and marked
      increase in helper T cells and with a smaller elevation in B cells; (iii)
      elevation in B cells, but not in T cells, is associated with long term
      mycobacteria-induced protection of NOD mice from IDDM.

PMID- 8864826
TI  - Yersinia enterocolitica envelope proteins that are crossreactive with the
      thyrotropin receptor (TSHR) also have B-cell mitogenic activity.
AB  - Autoantibodies to the thyrotropin receptor (TSHR) have been shown to mediate the
      hyperthyroidism associated with Graves' disease (GD). A number of hypotheses have
      been proposed which link an infectious agent to the mechanism(s) involved in the
      induction of GD. Several studies have suggested that the development of GD may be
      linked to infection with the enteric pathogen Yersinia enterocolitica. We have
      recently identified two low molecular weight (5.5 and 8 kDa) envelope proteins of
      Y. enterocolitica that are cross-reactive with the extracellular domain of human
      TSHR (ETSHR). In this study, we have purified these ETSHR-crossreactive Yersinia
      proteins (TSHR-CRP) and have further characterized their immunoreactivity. Both
      the 5.5 and 8 kDa TSHR-CRPs were shown to be mitogenic for mouse spleen cells.
      This mitogenic activity was specific for B cells and was not due to
      lipopolysaccharide (LPS) contamination. TSHR-CRPs were mitogenic for LPS-non
      responsive spleen cells obtained from C3H/Hej mice, and polymyxin B did not
      inhibit the mitogenic activity of the TSHR-CRPs. TSHR-CRPs also induced high
      levels of IL-6 production in B cells and induced production and secretion of
      significant levels of IgG and IgM. Finally, culture supernatants from TSHR-CRP
      stimulated spleen cells were shown by Western blot analysis to contain antibodies
      that recognized the ETSHR These results identify for the first time two envelope
      proteins of Yersinia that have mitogenic activity and therefore could represent
      important proteins involved in the pathogenesis of Yersinia infections. Because
      these mitogenic proteins also contain epitopes crossreactive with the TSHR, they
      are potentially important for advancing our understanding of the role molecular
      mimicry plays in the induction of autoimmunity to the TSHR.

PMID- 8864827
TI  - Detection of autoantibodies to the pancreatic islet heat shock protein 60 in
      insulin-dependent diabetes mellitus.
AB  - Autoantibodies against heat shock protein (hsp) 60 have been reported to be
      detected in sera of non-obese diabetic mice, in an experimental model of IDDM.
      However, there are only a few studies which have examined IDDM patients for
      antibodies against mammalian hsp60. We produced murine hsp60 derived from
      pancreatic beta cells which has high homology to human hsp60 and examined
      antibodies against the hsp60 in IDDM patients using an enzyme-linked
      immunosorbent assay. We extended the analysis to patients with other immune
      mediated diseases and non-insulin-dependent diabetes mellitus (NIDDM). Positive
      sera for hsp60 antibody were more frequently detected in 13 out of 84 IDDM
      (15.5%) and 5 out of 25 rheumatoid arthritis patients (20%), when compared to
      healthy subjects (1/85; 1.2%, P < 0.001 and P < 0.01, respectively). The levels
      of hsp60 antibodies of IDDM (0.218 +/- 0.227) and rheumatoid arthritis patients
      (0.259 +/- 0.191) were significantly higher than those of healthy subjects (0.076
      +/- 0.131, P < 0.001, P < 0.01, respectively). Patients with slowly progressive
      IDDM (n = 26), autoimmune thyroid disease (n = 42), or NIDDM (n = 40) had levels
      of hsp60 antibodies similar to those in healthy subjects. We found no
      relationship between the levels of hsp60 antibodies and islet cell antibodies
      (ICA) or antibodies to glutamic acid decarboxylase (GAD65) in IDDM patients. In
      conclusion, hsp60 antibodies were detected in Japanese IDDM as well as in
      rheumatoid arthritis patients. Although the positivity was low, the detection of
      hsp60 antibodies may be helpful for diagnosis of IDDM especially in GAD65 Ab- or
      JCA-negative Japanese patients.

PMID- 8864828
TI  - Cloning of candidate autoantigen carboxypeptidase H from a human islet library:
      sequence identity with human brain CPH.
AB  - A number of proteins, many of them enzymes, i.e. glutamic acid decarboxylase
      (GAD), carboxypeptidase H, 37-40 K tyrosine phosphatase (ICA512, IA2/IA2 beta),
      have been proposed as islet autoantigens involved in the pathogenesis of IDDM.
      Until recently, progress in their characterization has been impeded by the
      inaccessibility of the human pancreas, resulting in many of them being cloned
      from animal or non-islet sources. Carboxypeptidase H, one of these enzymes, has
      been cloned and sequenced from human brain and from rat islets but not from human
      islets. In this study, we describe the production of a human islet cDNA library
      and the cloning of islet CPH from it. Since CPH clones were also detected in a
      human thyroid library, we have sequenced CPH from these two endocrine tissue
      libraries and compared them to the known brain sequence. The sequences from
      islets and thyroid were identical and differed from brain only in the absence of
      a second ATG in the predicted 5'non-coding region. Northern blot analysis
      revealed the presence of an identical 2.5 kb transcript in human islets, thyroid
      and brain. The confirmation of the existence of a single isoform of CPH expressed
      in brain and endocrine tissues simplifies future experiments to elucidate the
      role of CPH as autoantigen.

PMID- 8864830
TI  - Autoantibody repertoire to Ro/SSA and La/SSB antigens in patients with primary
      and secondary Sjogren's syndrome.
AB  - Autoimmune diseases are characterized serologically by the presence of antibodies
      to specific autoantigens. Antibodies to the two antigens Ro/SSA and La/SSB are
      found in patients with primary (pSS) and secondary Sjogren's syndrome (sSS). To
      explore if differences in the fine specificity of these autoantibodies could be
      distinguished in sera from patients with primary (n = 17) and secondary (n = 20)
      Sjogren's syndrome, sera were analysed by immunoblotting and ELISA using
      recombinant antigens and synthetic peptides. Minor differences were detected when
      the frequencies of the Ro 60 kD, Ro 52 kD and La autoantibody specificities to
      full-length proteins in the pSS and sSS groups were compared. However, when
      reactivity to different parts of the Ro 60 kD antigen was analysed, including
      recombinant fragments encompassing amino acid (aa) 1-134, aa 181-320 and aa 397
      525, only two sera, both from pSS patients, reacted to the aminoterminal fragment
      aa 1-134, and 3/4 sera that reacted with the carboxyterminal aa 397-525 fragment
      derived from sSS patients. Of all the anti-Ro 60 kD positive sera, 80% reacted
      with the middle fragment encompassing aa residues 181-320. The fine specificity
      of the autoantibodies reacting with this 181-320 aa region was further mapped
      with synthetic peptides, and a peptide (VSLVCEKLCNEKLLKKARIH) recognized by 8 out
      of 16 sera from both pSS and sSS patients was identified.

PMID- 8864829
TI  - Purification and characterization of a recombinant human thyroid peroxidase
      expressed in insect cells.
AB  - Thyroid peroxidase (TPO) is an essential enzyme for thyroid hormone biosynthesis
      and is an autoantigen against which antibodies are found in a number of
      autoimmune thyroid disorders. Large quantities of pure TPO are essential for
      understanding its structure and role in normal thyroid function and thyroid
      diseases. In this study, we describe the production of human TPO (hTPO) using a
      baculovirus expression vector in insect cells. TPO was sequentially extracted
      from insect cells using various buffers and the protein was purified to
      homogeneity on a C4 reversed-phase semipreparative column using high-performance
      liquid chromatography. The purified protein was identified as hTPO by enzyme
      linked immunosorbent assay, Western blot, and amino acid sequence analyses.
      Carbohydrate analysis of the recombinant hTPO showed that the protein is
      glycosylated and mannose is the major oligosaccharide. We have extended the
      carbohydrate analysis by establishing the occurrence of N-acetyl galactosamine
      which suggested that the recombinant hTPO might contain O-glycosyl moieties.
      Purified hTPO reacted specifically with sera from patients with Hashimoto's
      thyroiditis. Crude as well as purified hTPO did not show any enzymatic activity
      when produced in Sf9 insect cells grown in serum free medium. In contrast, hTPO
      produced in the presence of 10% fetal bovine serum containing 1 microgram/ml of
      haematin was enzymatically active. However, the enzymatic activity of the
      recombinant hTPO was lower than that often found with hTPO purified from thyroid
      tissue. Availability of purified hTPO in relatively large quantities should allow
      further structural and immunological studies.

PMID- 8864831
TI  - Increased production of B cell growth factor (BCGF) in Sjogren's syndrome.
AB  - The objective of this investigation to clarify possible roles of B cell growth
      factor (BCGF) in the abnormal activation of B cells in Sjogren's syndrome (SS).
      Lymphocyte subsets of peripheral blood from 20 patients with SS (14 with primary
      SS and six with secondary SS) and 11 healthy donors were analysed by flow
      cytometry. Supernatants of peripheral blood T cells obtained from patients with
      SS and from donors, cultured with or without PHA, were studied using bioassay
      with a B cell line, KS-3.F10. The number of CD20+ cells and CD4+DR+ cells was
      significantly increased in SS patients compared with healthy donors. T cells from
      SS patients showed increased production of BCGF, whether or not they were
      stimulated with PHA. The enhancement of BCGF production by PHA had a positive
      correlation with the percentage of CD4+CD45RA+ cells, and a negative correlation
      with the focus score of lip biopsy. Our experiments showed that BCGF production
      by T cells was spontaneously increased in SS patients. The accelerated BCGF
      production with PHA stimulation may be related to the increase of CD4+CD45RA+
      cells and the decrease of the inflammation determined by the grade of cell
      infiltration into salivary glands, but not by the increase of CD20+ cells.

PMID- 8864832
TI  - Human anti-RNP sera contain both human-specific and cross-reactive anti-70K
      autoantibodies.
AB  - The U1 snRNP (small nuclear ribonucleoprotein complex) associated 70K protein is
      the main autoantigen for the anti-RNP autoantibodies which are directed against
      the U1 snRNP particle. The major antigenic region of the 70K protein has by
      various laboratories been mapped to an RNA binding domain required for the 70K-U1
      snRNA interaction. We have used recombinant proteins comprising this region from
      the human and the Drosophila melanogaster 70K proteins to examine the species
      specificity of the human anti-70K autoantibodies found in 42 patient sera. Most,
      but not all, anti-70K positive sera in this cross-sectional sample contained both
      human 70K specific anti-bodies and Drosophila 70K reactive antibodies. Results of
      a longitudinal follow-up of 14 patients indicated that the cross-reactive anti
      70K antibodies developed secondarily to the establishment of a species-specific
      anti-70K reaction. In a fraction of the patient sera this broadening of the
      response never occurred. Taken together, the data in this study support the
      hypothesis that the endogenous human 70K protein is the immunogen driving the
      production of anti-70K autoantibodies.

PMID- 8864833
TI  - Placental and fetal cardiac laminin are targets for cross-reacting autoantibodies
      from mothers of children with congenital heart block.
AB  - The association of congenital heart block (CHB) with maternal autoantibodies to
      the Ro and La ribonucleoprotein antigens may be due to cross-reactions between
      maternal anti-La antibodies and fetal cardiac specific antigens. One of the major
      components of cardiac myocytes, laminin, is accessible for binding by maternal
      autoantibodies and we have previously reported cross-reactivity of mouse laminin
      with anti-La antibodies affinity purified from the sera of patients with primary
      Sjogren's syndrome. Affinity purified anti-La antibodies from ten women who had
      at some time given birth to a child with CHB were examined for cross-reactivity
      with human placental laminin, which shares structural similarities with cardiac
      laminin. All ten anti-La antibodies bound to the surface of cryosections of
      normal full term placental trophoblasts. Binding could be inhibited by pre
      incubation of antibodies with either La or placental laminin. Eight anti-La
      antibodies also reacted with placental laminin by ELISA and La inhibited up to
      82% of binding to laminin while laminin inhibited up to 85% of binding to La in a
      dose dependent manner. Eight anti-La antibodies also bound to the surface of
      fetal cardiac myocytes at 10.3 weeks of gestation and five showed lower levels of
      reactivity with the surface of fetal cardiac myocytes at 16.5 weeks of gestation.
      None showed any surface staining of normal adult heart. These data confirm the
      cross-reactivity of anti-La antibodies with laminin and may support a placental
      role in preventing the majority of potentially pathogenic antibodies from
      reaching the fetal circulation.

PMID- 8864834
TI  - Anti-lactoferrin autoantibodies: relation between epitopes and iron-binding
      domain.
AB  - Anti-neutrophil cytoplasm antibodies (ANCA) have been found in the sera of
      patients presenting systemic necrotizing microscopic vasculitis, i.e. Wegener's
      granulomatosis and microscopic polyangiitis. Lactoferrin (LF) is one of the
      antigens rarely recognized by ANCA, and anti-LF autoantibodies are found in
      several autoimmune conditions, including rheumatoid vasculitis, rheumatoid
      arthritis, systemic lupus erythematosus, ulcerative colitis, primary sclerosing
      cholangitis and Crohn's disease. We analysed the epitopes recognized by human
      anti-LF antibodies to test whether the heterogeneity of clinical presentation
      might be due to a different epitope recognition profile. Several monoclonal
      antibodies were raised and used in competition studies with six human sera. Four
      distinct epitopes were identified on LF, and LF binding of only one of six sera
      was inhibited by one of the monoclonals. Thus, anti-LF autoreactivity appears to
      be polyclonal and not restricted to an immunodominant epitope. Specific epitope
      profiles cannot be determined in these autoimmune conditions. We hypothesized
      that the interaction of anti-LF antibodies with the LF iron binding domain might
      contribute to pathogenesis by inhibiting iron chelation after neutrophil
      activation, thereby providing increased iron availability for endothelial cell
      damage. The relation of anti-LF mouse monoclonals or polyclonal human or rabbit
      antibodies to the LF iron-binding domain was studied in competition assays
      between 59Fe and these antibodies. Preincubation of LF with monoclonals or anti
      LF human sera did not affect the binding of 59Fe on LF. 59Fe-binding kinetic
      studies showed that rabbit anti-LF polyclonal, but not mouse monoclonals or human
      anti-LF positive sera, was capable of inhibiting iron binding on LF. Therefore,
      anti-LF autoantibodies did not appear to modulate LF iron-binding activity. We
      conclude that LF is a rare antigen specificity for ANCA and that the clinical and
      pathophysiological relevance of anti-LF autoreactivity remains uncertain.

PMID- 8864835
TI  - Molecular cloning and functional analysis of sialyltransferases.
AB  - To elucidate the regulatory mechanism for carbohydrate expression and to
      understand the meaning of the carbohydrate-structural diversity, we started to
      clone sialyltransferase (ST) genes based on two different strategies, i.e.
      expression and homology cloning. So far, 13 STs have been cloned in our
      laboratory, 7 of which turned out to be new ones. The primary enzyme structures
      deduced from all the cloned ST genes suggest a putative domain structure with a
      type II transmembrane topology. There are no significant amino acid sequence
      similarities among these cloned STs, except for in two sialyl motifs, L and S,
      which are proposed to be the CMP-sialic acid recognition and/or catalytic sites.
      Northern blot analysis revealed the developmental stage-dependent and/or tissue
      specific expression of most of the cloned STs. The cloned STs are classified into
      four families according to the carbohydrate linkages they synthesize, i.e. the
      ST3Gal-, ST6Gal-, ST6GalNAc-, and ST8Sia-families. Generally, enzymes in these
      families exhibit strong activity toward certain acceptor groups but show very
      weak activity toward other acceptor groups, and the substrate specificities of
      the enzymes overlap one another, as indicated by in vitro experiments. Enzymes in
      the ST3Gal-family are expressed mainly in a tissue-specific manner. However,
      those in the ST6GalNAc- and ST8Sia-families are expressed in a tissue-as well as
      developmental stage-specific manner. In vivo conditions are supposed to be more
      complex. Therefore, it is quite important to examine their substrate
      specificities in vivo and the mechanism of their expression to elucidate the
      physiological role of each enzyme and the meaning of the diversity in
      carbohydrate structure. Using cloned cDNAs and expressed enzymes, we have been
      studying how sialylcarbohydrate expression is regulated and what the functions of
      sialylcarbohydrate chains are. Recently, we found that transfection of the GD3
      synthase, an alpha 2,8-ST (ST8Sia I), gene triggers cholinergic neuritogenesis in
      Neuro2a cells through the de novo expression of GD3, suggesting that the GD3
      synthase gene behaves as a neural differentiation inducer.

PMID- 8864836
TI  - Three-dimensional structure of porcine kidney D-amino acid oxidase at 3.0 A
      resolution.
AB  - The X-ray crystallographic structure of porcine kidney D-amino acid oxidase,
      which had been expressed in Escherichia coli transformed with a vector containing
      DAO cDNA, was determined by the isomorphous replacement method for the complex
      form with benzoate. The known amino acid sequence, FAD and benzoate were fitted
      to an electron density map of 3.0 A resolution with an R-factor of 21.0%. The
      overall dimeric structure exhibits an elongated ellipsoidal framework. The
      prosthetic group, FAD, was found to be in an extended conformation, the
      isoalloxazine ring being buried in the protein core. The ADP moiety of FAD was
      located in the typical beta alpha beta dinucleotide binding motif, with the alpha
      helix dipole stabilizing the pyrophosphate negative charge. The substrate analog,
      benzoate, is located on the re-face of the isoalloxazine ring, while the si-face
      is blocked by hydrophobic residues. The carboxylate group of benzoate is ion
      paired with the Arg283 side chain and is within interacting distance with the
      hydroxy moiety of Tyr228. The phenol ring of Tyr224 is located just above the
      benzene ring of benzoate, implying the importance of this residue for catalysis.
      There is no positive charge or alpha-helix dipole near N(1) of flavin. Hydrogen
      bonds were observed at C(2) = O, N(3)-H, C(4) = O, and N(5) of the flavin ring.

PMID- 8864838
TI  - Identification of a ribosomal frameshift in Leishmania RNA virus 1-4.
AB  - Double-stranded Leishmania RNA virus 1-4 (LRV 1-4) has at least four open reading
      frames (ORFs). The two small ORFs located near its 5' terminus, ORF1 and ORFx,
      could encode 34- and 60-amino acid polypeptides, respectively. ORF2 encodes an 82
      kDa major capsid protein, and ORF3 encodes a 98-kDa polypeptide which contains
      the consensus sequence for RNA-dependent RNA polymerases of plus-strand and
      double-stranded RNA viruses. The complete sequence of LRV 1-4 shows that ORF2 and
      ORF3 overlap by 71 nucleotides, and that ORF3 lacks a potential translation
      initiation site, suggesting that the viral polymerase may be synthesized as a 180
      kDa fusion protein with the virus capsid. In this report, we present evidence for
      the synthesis of a fusion protein through a ribosomal frameshift. In vitro
      translation experiments and immunostudies involving antiserum against the viral
      capsid protein demonstrated that the overlapping 71 nucleotides of ORF2 and ORF3
      are contained in a region which promotes translational frameshifting. Computer
      analysis of the putative frameshift region revealed a potential pseudoknot
      structure located within the overlapping 71 nucleotide sequence.

PMID- 8864837
TI  - The 5'-flanking region of the human smooth muscle cell calponin gene contains a
      cis-acting domain for interaction with a methylated DNA-binding transcription
      repressor.
AB  - The human smooth muscle cell (SMC) calponin gene, which is composed of seven
      exons and six introns, spanning an approximately 11.2 kilobase (kb) genomic DNA,
      has been isolated and characterized by sequence analysis. As determined by primer
      extension mapping and rapid amplification of mRNA transcripts, a major
      transcription start site of the calponin gene is located at 101 base-pairs (bp)
      upstream of the ATG start codon. A striking feature of the 5'-flanking, 5'
      untranslated, and amino-terminal protein coding regions is the presence of an Alu
      repetitive sequence and a stretch of DNA sequence identified using a methyl CpG
      binding protein affinity column [Cross, S.H., Charlton, J.A., Nan, X., and Bird,
      A.P. (1994) Nature Genet, 6,236-244]. The results of this study provide a new
      insight into the molecular mechanism underlying regulation of SMC-lineage
      specific gene expression.

PMID- 8864839
TI  - A preliminary description of the crystal structure of gamma
      glutamyltranspeptidase from E. coli K-12.
AB  - The structure of GGT [EC 2.3.2.2] from E. coli K-12 was studied at 3 A resolution
      by X-ray crystallography. Initial protein phases were calculated using two kinds
      of Pb2+ derivatives. The phases were refined by non-crystallographic 2-fold
      symmetry electron density averaging combined with solvent flattening and
      histogram matching. The GGT molecule has overall dimensions of 60 x 50 x 40 A.
      There are two antiparallel beta-pleated sheets consisting of 6 and 7 beta
      strands. The two beta-sheets form a wall-like structure. Twelve short alpha
      helices were detected, of which the maximum length appears to be four helix
      turns.

PMID- 8864840
TI  - Systematic peptide fragmentation of polyvinylidene difluoride(PVDF)-immobilized
      proteins prior to microsequencing.
AB  - The sequential in situ digestion of proteins immobilized on polyvinylidene
      difluoride (PVDF) has been systematically designed and optimized. The method
      consists of immobilization of the proteins on PVDF, S-carboxymethylation, and
      then successive in situ digestions using specific proteases. In order to obtain
      high yields of the peptide fragments, from which specific amino acid residues
      connected to the N- or C-terminal of the resulting digestion fragments can be
      deduced, the cleavages are performed in the following order: (1) Achromobacter
      protease I (API), (2) endoproteinase Asp-N, and (3) trypsin. Procedures for
      recovering the numerous fragments remaining on the PVDF membrane after the third
      digestion with trypsin are also discussed. Application of sequential in situ
      digestion for the acquisition of fragments suitable for sequencing from digests
      of large-molecular-weight proteins is also presented.

PMID- 8864841
TI  - Dephosphorylation of cofilin in parotid acinar cells.
AB  - Cofilin is an actin-depolymerizing protein, whose depolymerizing activity is
      supposed to be regulated in part by phosphorylation and dephosphorylation. Thus,
      we studied the phosphorylation states of cofilin in rat parotid acinar cells
      during stimulation for amylase exocytosis. Isoproterenol and carbachol induced
      rapid and extensive dephosphorylation of cofilin; 60-70% dephosphorylation was
      clearly detectable within 1 min. Membrane-permeable cyclic AMP (CPS-cAMP),
      phorbol ester (PMA), and Ca ionophore A23187 mimicked the effect of isoproterenol
      and carbachol. Protein phosphatase inhibitors (calyculin A or FK506 plus
      cyclosporin A) did not block the dephosphorylation in response to isoproterenol
      or carbachol. Furthermore, calyculin A alone strongly dephosphorylated cofilin.
      Although no exogenous protein phosphatases tested dephosphorylated cofilin in the
      homogenate, the cofilin that was isolated by immunoprecipitation was clearly
      dephosphorylated by protein phosphatases 1, 2A, and 2C.

PMID- 8864842
TI  - Application of primary hepatocytes from p53-knockout mice for studies of
      expression of Cyp3a.
AB  - CYP3A rapidly disappears in primary hepatocytes, although the primary cells are
      suitable for studies of the regulation of CYP3A genes. In the present study, we
      found that Cyp3a mRNA could be expressed in the primary hepatocytes from p53
      knockout mice for at least 2 weeks when the cells were cultured in the presence
      of dexamethasone. Propoxycoumarin O-depropylase activity, which is known to be
      mainly catalyzed by CYP3A, was maintained at a level of 50% of the initial
      activity even after 5 days of culture, and the activity correlated with the
      expression level of Cyp3a mRNA in the primary hepatocytes from p53-knockout mice.
      The cells remained morphologically intact during 4 weeks. These results suggest
      that hepatocytes from p53-knockout mice are a useful tool for studies of the
      expression of Cyp3a.

PMID- 8864843
TI  - Concomitant transcriptional activation of nitric oxide synthase and heme
      oxygenase genes during nitric oxide-mediated macrophage cytostasis.
AB  - During in vitro activation of mouse peritoneal macrophages with interferon-gamma
      (IFN-gamma) and lipopolysaccharide (LPS), their synthesis of peroxynitrite and
      their cytostatic activity against mouse lymphocytic leukemia (L1210) cells were
      examined. The activation of the genes for nitric oxide synthase (iNOS) and heme
      oxygenase (HO-1) was also determined during the activation of the macrophages.
      Results showed that activation of peroxynitrite synthesis in macrophages was
      accompanied by the transcriptional activation of iNOS and HO-1 genes. Both genes
      seem to be activated simultaneously upon activation of the macrophages.
      Simultaneous activation of iNOS and HO-1 genes may be important because
      degradation of heme by HO-1 is one of the most important reaction that produces
      CO in higher organisms, and nitric oxide (NO) and carbon monoxide (CO) can react
      with heme-containing guanylate cyclase.

PMID- 8864844
TI  - Factors involved in the activation of pre-mRNA splicing from downstream splicing
      enhancers.
AB  - The excision of introns with weak polypyrimidine tracts at their 3' splice sites
      can be enhanced by sequence elements in the downstream exon or by a downstream 5'
      splice site. The enhancers inside the exon do not conform to a strict consensus,
      but they are generally rich in purines. Here, we show that members of the family
      of SR proteins recognize these elements. Not only does SF2/ASF activate many
      different polypurine enhancers, but also at least one other SR protein, most
      likely SC35, is active as well. The degree of splicing activation varies with the
      polypurine enhancers and the SR proteins. Further, we show that the similar
      activation by downstream 5' splice sites requires U1 snRNP, which is not the case
      with purine-rich enhancers. These results are consistent with a model showing
      that U1 snRNP binds to the 5' splice site and SR proteins to exonic sequences
      upstream of the 5' splice site. Both interact with U2AF at the 3' splice site.
      This represents a molecular explanation for the exon recognition which is
      important for splice site selection in mammals.

PMID- 8864846
TI  - Interaction of ganglioside with specific peptide sequences as a mechanism for the
      modulation of calmodulin-dependent enzymes.
AB  - We examined the interaction between gangliosides and synthetic peptides of
      calmodulin (CaM)-dependent enzymes to confirm the hypothesis that interaction
      between gangliosides and the CaM-like site (CLS) of the enzyme is a mechanism for
      the modulation of the enzyme activity by gangliosides. Gangliosides, GD1b, GT1b,
      and GD1a, inhibited the activity of CaM-independently activated cAMP
      phosphodiesterase and their inhibition was cancelled by a peptide consisting of
      17 amino acid residues of a plasma membrane Ca(2+)-pump CLS, suggesting the
      involvement of the interaction between the peptide and the gangliosides. The
      peptide of an assumed CLS of phosphodiesterase also cancelled the inhibition. On
      the other hand, the gangliosides interacted with synthetic CaM-binding site (CBS)
      peptides of phosphodiesterase, calcineurin, Ca(2+)-pump, and Ca2+/calmodulin
      dependent protein kinase II. Moreover, gangliosides GM3 and LM1, that activate
      but do not inhibit phosphodiesterase, interacted with the CBS peptides, whereas
      they did not bind to CLS peptides. On the basis of these new findings, we propose
      a revised model for the ganglioside-mediated modulation of CaM-dependent enzymes,
      i.e. without CaM, gangliosides bind to CBS and thus stimulate the enzyme
      activity, acting like CaM. At higher concentrations, they bind to CLS of the
      enzymes as well and inhibit the activity, acting like the CBS of the enzyme.

PMID- 8864845
TI  - Sphingosine enhances phosphatidylinositol 4-kinase activity in rabbit platelets.
AB  - The modulating effect of sphingosine on the metabolism of inositol phospholipids
      was investigated using rabbit platelets. When [3H]arachidonic acid- or
      [3H]inositol-labeled platelets were incubated at 37 degrees C with sphingosine,
      the radioactivity of the phosphatidylinositol (PI) fraction obtained on TLC
      decreased time-dependently up to 5 min, and phosphatidylinositol monophosphate
      (PIP) and phosphatidylinositol bisphosphate (PIP2) increased concomitantly,
      though neither arachidonic acid nor 1,2-diacylglycerol was formed. The effect of
      sphingosine was dose-dependent, the maximum effect being observed at 20 microM.
      Treatment with a sphingosine derivative, sphingosine-1-phosphate (Sph-1-P) or N
      hexanoyl-sphingosine (C6-ceramide), did not result in an increase in PIP. The
      increased radioactivity of PIP with sphingosine was attributable to an increase
      in phosphatidylinositol 4-phosphate, but not phosphatidylinositol 3-phosphate.
      Furthermore, wortmannin, an inhibitor of PI 3-kinase, did not affect the
      modulating effect of sphingosine at 100 nM, at which the enzyme is known to be
      completely inhibited. The activity of PI 4-kinase in the platelet lysate was
      increased by sphingosine but not by Sph-1-P. These results suggest that
      sphingosine enhances the activity of PI 4-kinase and thereby contributes to the
      regulation of inositol phospholipid metabolism.

PMID- 8864847
TI  - Characterization of seed oil bodies and their surface oleosin isoforms from rice
      embryos.
AB  - Plant seeds store triacylglycerols in discrete organelles called oil bodies. An
      oil body stores a matrix of triacylglycerols surrounded by phospholipids and
      alkaline proteins termed oleosins. Oil bodies in rice seeds are present in
      embryos and aleurone layers. They do not coalesce in crowded environments, as
      observed on electron microscopy. The detected isoelectric point of purified rice
      oil bodies is pH 6.2. This implies that rice oil bodies possess a negatively
      charged surface at neutral pH. The suspension of rice oil bodies in pH 6.5 buffer
      induces aggregation. Presumably, the negatively charged surface causes
      electrostatic repulsion that maintains rice oil bodies as discrete organelles.
      Rice oil bodies lose their integrity on trypsin treatment. Undoubtedly, oleosins
      play an important role in the stability of oil bodies. There are two oleosin
      isoforms in rice oil bodies. Antibodies raised against these two homologous
      isoforms do not cross-recognize each other. Both isoforms are restricted to oil
      bodies, as detected on immuno-assaying. Partial amino acid sequences of these two
      isoforms were obtained, and compared with the deduced sequences of two maize and
      two rice oleosin genes. The comparison confirmed that the two major proteins in
      rice oil bodies are the two oleosin isoforms.

PMID- 8864848
TI  - Conserved histidine residues of RCC1 are essential for nucleotide exchange on
      Ran.
AB  - Charged amino acid residues of human RCC1 were converted to alanine and mutants
      which were unable to complement tsBN2 cells (a temperature-sensitive rcc1- mutant
      of the hamster BHK21 cell line) were selected. These RCC1 mutants were analyzed
      for the ability to inhibit premature chromatin condensation by microinjection
      into tsBN2 cells, and their steady-state kinetic parameters for guanine
      nucleotide exchange reaction were measured. Examined RCC1 mutants were unstable
      in tsBN2 cells at the restrictive temperature, yet they significantly inhibited
      premature chromatin condensation. Mutants located on the N-terminus of the RCC1
      repeat showed an increased K(m), while their kcat values were comparable to that
      of wild-type RCC1. In contrast, mutants containing the conserved histidine
      residues in the C-terminus of the RCC1 repeat showed a value of K(m) similar to
      that of wild-type RCC1, while the kcat values of these mutants were reduced,
      depending upon the RCC1 repeats on which the mutation was located. These steady
      state kinetic parameters of mutants indicate that the N-terminus and the C
      terminus of RCC1 repeats play different roles in guanine nucleotide exchange on
      Ran. The comparison of kcat among the histidine mutants suggests that those
      histidine residues which are conserved in the RCC1 repeats and also through
      evolution comprise the catalytic site for the guanine nucleotide exchange
      reaction.

PMID- 8864849
TI  - Abundance of Gal beta 1,3GalNAc in O-linked oligosaccharide on hinge region of
      polymerized IgA1 and heat-aggregated IgA1 from normal human serum.
AB  - Gas-phase hydrazinolysis was used to analyze the glycoform of the O-linked
      oligosaccharide of human serum IgA1. In our previous report, only one glycoform
      was obtained from the IgA1 of healthy individuals. However, it was found to be
      composed of heterogeneous IgA1 components having mutually different glycoforms.
      First, the IgA1 was separated into two subfractions having different affinities
      toward jacalin. Among them, the high-affinity subfraction was mainly composed of
      polymerized IgA1. Comparative study of the carbohydrate chain showed a relative
      abundance of Gal beta 1,3GalNAc in the polymerized form. A simultaneous analysis
      of the N-glycan of these subfractions was also carried out. Three major
      components, two biantennary and one triantennary oligosaccharides, were obtained
      from both subfractions and the relative contents of these components were almost
      the same. On the other hand, IgA1 was artificially polymerized by heating at 63
      degrees C for 2 h. The heat-stable IgA1 was separated from the heat-aggregated
      material on a Sephacryl S-300 column. The obtained heat-stable IgA1
      (approximately 20%) was not further aggregated by more heating under the same
      conditions. The heat-stable IgA1 contained a much higher amount of the sialylated
      Gal beta 1,3GalNAc. Thus, it was shown that the degree of completeness of the
      hinge O-linked oligosaccharide might be correlated with the stability and
      polymerization process of the IgA1 molecule.

PMID- 8864850
TI  - Purification and characterization of the Proteus vulgaris BlaA protein, the
      activator of the beta-lactamase gene.
AB  - Induction of the expression of the beta-lactamase gene, blaB, is regulated by the
      blaA gene located just upstream of blaB in the opposite direction in Proteus
      vulgaris. The expression of the blaA gene is negatively autoregulated by its own
      product BlaA, the activator of the blaB gene. The P. vulgaris BlaA protein shares
      high amino acid homology with the LysR family members, which are prokaryotic
      transcriptional activators that possess a putative helix-turn-helix DNA binding
      motif. To characterize its function, we purified the BlaA protein to homogeneity
      from Escherichia coli carrying the expression plasmid of the blaA gene driven by
      the tac promoter. The gel shift assay and DNaseI footprinting showed that
      purified BlaA specifically bound to the blaA promoter region, which resides
      immediately upstream of that of blaB. The binding region contained an inverted
      repeat, including a T-N11-T sequence which is similar to the LysR motif (T-N11-A)
      that is conserved in some LysR family members [Goethals et al. (1992) Proc. Natl.
      Acad. Sci. USA 89, 1646-1650]. We also showed that the BlaA protein forms a dimer
      in solution, using glycerol gradient centrifugation and glutaraldehyde
      crosslinking.

PMID- 8864851
TI  - Purification and characterization of a marine bacterial beta-galactoside alpha
      2,6-sialyltransferase from Photobacterium damsela JT0160.
AB  - A bacterial sialyltransferase, named sialyltransferase 0160, was purified from a
      marine bacterium that had been isolated from seawater from Sagami Bay, Kanagawa.
      This strain has been identified as Photobacterium damsela, and named P. damsela
      JT0160. Sialyltransferase 0160 was purified 688-fold to homogeneity from the
      crude extract of the cells with a yield of 19% using a combination of anion
      exchange chromatography, hydroxyapatite chromatography, gel filtration
      chromatography, and affinity chromatography. The purified enzyme migrated as a
      single band (61 kDa) on sodium dodecyl sulfate-polyacrylamide gel. This
      sialyltransferase was found to be a beta-galactoside alpha 2,6-sialyltransferase
      [EC 2.4.99.1] which catalyzes the incorporation of NeuAc from CMP-NeuAc into the
      galactose residue of the carbohydrate chain at position 6 on the basis of an
      analysis of the enzymatic reaction products with HPLC, 1H-, 13C-NMR spectroscopy,
      and fast atom bombardment mass spectroscopy.

PMID- 8864852
TI  - Signal transduction pathways for interleukin 4 and insulin in human hepatoma
      cells.
AB  - IRS-1 has been found to relay the signals from the receptors for insulin, insulin
      like growth factor-1, growth hormone, and many cytokines for the downstream
      effects in the various cell types tested. For interleukin 4 signaling, most
      studies were performed on hematopoietic cells and cell lines transfected with rat
      liver IRS-1 cDNA. In a liver cell lineage, IRS-1 expression has been found to be
      increased in hepatoma cells and hepatocytes in regenerating liver. To elucidate
      the possible function and the signal transduction pathway for interleukin 4, in
      comparison with insulin, in liver cells, we used the Hep 3B hepatoma cell line as
      a model system. Following insulin and interleukin 4 stimulation, rapid tyrosyl
      phosphorylation of IRS-1 occurred. Interleukin 4, but not insulin, stimulated the
      tyrosine phosphorylation of JAK1 and, to a lesser extent, JAK2. In contrast to
      the other cell types, the association of IRS-1 and Grb2 through the SH2 of Grb2
      was demonstrated after IL-4 and insulin stimulation of the Hep3B hepatoma cells.
      Both insulin and interleukin 4 stimulated tyrosine phosphorylation and the enzyme
      activity of Erk1 kinase. Our results indicate that interleukin 4 and insulin
      might modulate hepatic cell growth and differentiation through many different or
      common pathways for the activation of JAK kinases and the usage of IRS-1 as a
      docking protein. The binding of IRS-1 with Grb2 after IL-4 as well as insulin
      stimulation may lead to MAP kinase activation, probably through the
      Grb2/sos/p21ras pathway.

PMID- 8864853
TI  - Keratan sulfate synthesis by corneal stromal cells within three-dimensional
      collagen gel cultures.
AB  - The corneal stromal cells from 2-day-old chicks were cultured on plastic dishes
      or within three-dimensional collagen gel in the presence or absence of growth
      factor (EGF, bFGF, PDGF, TGF-beta 1, or their combinations). The cells were
      labeled with [35S] sulfate and [3H]-glucosamine, and the radio-labeled
      proteoglycans were examined. Keratan sulfate was synthesized to some extent (15.4
      16.9% of total synthesis for medium fraction; 8.0% for cell layer fraction) in a
      primary culture even when the cells were cultured on plastic dishes, although the
      values were very much lower than that (42.7%) in the stromal fraction of organ
      culture of corneal explants. The primary culture in collagen gel showed some
      increase in the proportion of keratan sulfate synthesis as compared with the
      culture on plastic. Among growth factors, addition of EGF to the culture in gel
      caused a further increase in the proportion of keratan sulfate synthesis. bFGF
      and TGF-beta 1 increased proteoglycan synthesis as a whole to some extent, but
      chondroitin sulfate/dermatan sulfate synthesis was increased preferentially and,
      consequently, the proportion of keratan sulfate synthesis to total synthesis was
      decreased. PDGF also caused some decrease in the proportion. In the culture after
      one passage (secondary culture), the keratan sulfate synthesis decreased markedly
      (8.6-8.3% of total synthesis for medium fraction; 2.7% for cell layer or gel
      fraction) and a large chondroitin sulfate/dermatan sulfate proteoglycan appeared
      whether the cells were cultured on plastic or in collagen gel. But, when the
      medium was changed to CG medium (serum-free medium) in the middle of either
      primary or secondary cultures, the keratan sulfate synthesis (27.8% for medium
      fraction; 15.6% for gel fraction) was maintained at the level of that of the
      primary culture in gel. EGF and bFGF were not additive to the effect of CG medium
      on the keratan sulfate synthesis in the secondary culture. Instead, EGF and bFGF
      stimulated hyaluronic acid synthesis in the culture. The mechanism of these
      changes in the expression type of proteoglycan and their significance remain to
      be clarified.

PMID- 8864854
TI  - H NMR probes for inter-segmental hydrogen bonds in myoglobins.
AB  - NMR signals arising from the HisB5 N delta H and HisEF5 N epsilon H protons in
      sperm whale skeletal and horse heart myoglobins have been located for the first
      time in the downfield shifted portion of the spectra. The shifts and hydrogen
      exchange rates indicate that these His imidazole ring NH protons are involved in
      the inter-segmental hydrogen bonds of the protein in solution, as demonstrated by
      a crystallographic study [Takano, T. (1977) J. Mol. Biol. 220, 381-399]. The
      assigned His imidazole ring NH proton resonances can serve as new sensitive
      structural probes in the study of the local conformation of myoglobin. The
      applicability of the NMR spectral parameters in the study of the tertiary
      structure of apomyoglobin, the denaturation of the protein, and the protein
      stability of sperm whale and horse myoglobins is presented in some detail.

PMID- 8864855
TI  - The 160k alpha 1(IV) chain, a short form of a type IV collagen polypeptide, of
      bovine lens capsule retains the NC1 domain.
AB  - We recently reported that the bovine lens capsule contained a shorter alpha 1(IV)
      chain (160k) as a major polypeptide in addition to the 180k alpha 1(IV) chain [J.
      Biochem. (1995) 117, 1298-1304]. Two experiments were performed to examine
      whether or not the 160k polypeptide retained the carboxyl-terminal NC1 domain. On
      immunoblotting analysis with a monoclonal antibody (H11) raised against the NC1
      domain of the human alpha 1(IV) chain [positions 1643-1650; near the carboxyl
      terminal end of the human alpha 1(IV) chain], the 180k and 160k polypeptides
      showed identical immunoreactivity, suggesting that the two chains had the same
      human alpha 1(IV) collagen NC1 domain sequence. Another monoclonal antibody (H21)
      specific for the NC1 domain of human alpha 2(IV) did not react with these
      polypeptides, but with the bands corresponding to 175k and 155k. The 160k
      polypeptide was selectively solubilized from bovine lens capsules, leaving the
      other major polypeptides, 180k and 175k, insoluble. The 160k polypeptide was
      separated by preparative electrophoresis. Bacterial collagenase digestion of the
      separated 160k polypeptide produced collagenase-resistant segments of about 29k
      and 30k in size based on globular standards. These sizes corresponded well with
      those of the NC1 domains of type IV collagen alpha chains (25-30k). The results
      indicated that the 160k polypeptide retained the carboxyl-terminal NC1 domain of
      the alpha 1(IV) chain. In turn, the 20k polypeptide of the amino-terminal region
      or the 7S domain of 180k alpha 1(IV) would have been excised to yield 160k alpha
      1(IV), assuming that the 160k alpha 1(IV) chain is a processed form of the 180k
      alpha 1(IV) one and not an alternatively spliced chain of the alpha 1(IV) gene.

PMID- 8864856
TI  - Effect of unsaturated fatty acids and antioxidants on immunoglobulin production
      by mesenteric lymph node lymphocytes of Sprague-Dawley rats.
AB  - The effect of UFA on Ig production by rat MLN lymphocytes was examined to clarify
      their influence on allergic reactions. A 4-h treatment at 1 mM inhibited the
      production of IgA, IgG, and IgM by the lymphocytes, but stimulated IgE
      production. The IgE production-stimulating activity became stronger with
      increasing number of carbon atoms and/or double bonds. However, no saturated
      fatty acid with carbon numbers from 12 to 18 affected IgE production by the
      lymphocytes. Hydrogen peroxide exerted Ig production-regulating activity similar
      to that of UFA, suggesting that the effect of UFA is at least partly due to
      oxidation products. Thus, the effect of antioxidants on the Ig production
      regulating activity of arachidonic acid was examined. alpha-Tocopherol and BHT
      annulled the stimulation of IgE production by arachidonic acid, but ascorbic acid
      was not effective. The IgE production-enhancing activity of UFA was closely
      related to their oxidation rate in culture medium. These results suggest that UFA
      enhance the allergic reaction through the stimulation of IgE production and the
      inhibition of IgA production, and that hydrophobic antioxidants are partially
      effective to annul the adverse effect of UFA.

PMID- 8864857
TI  - Inter-alpha-trypsin inhibitor and its related proteins in Syrian hamster urine
      and plasma.
AB  - Urinary excretion of trypsin inhibitor increased after injection of a carcinogen,
      N-nitrosobis(2-oxopropyl)amine, into Syrian hamsters. Two inhibitors were
      purified to apparent homogeneity from urine collected during the course of the
      carcinogenesis experiment. Their complete amino acid sequences were determined by
      Edman degradation of the intact proteins and partially degraded fragments. One
      corresponded to a hamster liver cDNA clone that hybridized with human bikunin
      probe [Ide et al, (1994) Biochim, Biophys. Acta 1209, 286-292], except that the
      protein sequence lacked C-terminal serine and the other was trypstatin, the C
      terminal half of the bikunin molecule. Three proteins containing covalently
      linked bikunin were also identified in pooled blood plasma. They were all
      dissociated into heavy and light chains by treatment with chondroitinase ABC or
      50 mM NaOH, but not by heating at 100 degrees C in the presence of sodium dodecyl
      sulfate and dithiothreitol, N-terminal amino acid sequence analyses of the native
      chains and partially degraded fragments thereof revealed that these proteins are
      (i) human-type inter-alpha-trypsin inhibitor, consisting of heavy chains 1 and 2
      and bikunin, (ii) bovine-type inter-alpha-trypsin inhibitor, consisting of heavy
      chains 2 and 3 and bikunin, and (iii) pre-alpha-trypsin inhibitor, consisting of
      heavy chain 3 and bikunin. Heterodimer of bikunin/heavy chain 1 or bikunin/heavy
      chain 2 was not detected. These results suggest that the composition, and hence
      function, of the inter-alpha-trypsin inhibitor family differs considerably from
      species to species.

PMID- 8864858
TI  - Human homolog of Drosophila heterochromatin-associated protein 1 (HP1) is a DNA
      binding protein which possesses a DNA-binding motif with weak similarity to that
      of human centromere protein C (CENP-C).
AB  - Heterochromatin-associated protein 1 (HP1) is a nonhistone chromosomal component
      tightly associated with the pericentromeric heterochromatic region of fruit fly,
      mouse, and human throughout the cell cycle. Drosophila HP1 has been shown to be
      involved in position effect variegation and to be required for the correct
      chromosome segregation in vivo, while the biological activity of human homolog
      (HP1Hsa) has not yet been characterized. We previously reported that human CENP-B
      and CENP-C, two major centromere heterochromatin autoantigens often recognized by
      autosera in scleroderma patients, possess DNA-binding activity in vitro. Here, we
      show that human HP1, which is also an autoantigen targeted by some types of
      anticentromere autosera, is a DNA-binding protein. Human HP1 was expressed as a
      GST-fusion in Escherichia coli and purified with glutathione-Sepharose. The DNA
      binding activity of the recombinant HP1 was demonstrated by gel mobility shift
      assay and South-Western-type blotting. The minimum DNA-binding region was further
      limited to the internal 64-amino acid stretch that is less-conserved between
      human and fruit fly but retains a helix-enriched motif with weak similarity to
      CENP-C. This suggests that HP1 is involved in the pericentromeric heterochromatin
      formation by directly associating with genomic DNA.

PMID- 8864859
TI  - Autocrine amplification of type I interferon gene expression mediated by
      interferon stimulated gene factor 3 (ISGF3).
AB  - Interferon regulatory factor (IRF)-1 and IRF-2 have been implicated for the virus
      induced expression of the interferon-alpha and beta (type I IFN) genes. However,
      recent gene disruption studies in mice suggested the presence of other factor(s)
      interacting with overlapping promoter elements. In the present paper, we describe
      the characterization of a DNA binding factor which is strongly induced after
      virus infection and recognizes these promoter elements. After extensive
      purification, the factor was revealed to be identical to IFN-stimulated gene
      factor 3 (ISGF3), a transcription factor complex activated by IFN treatment.
      ISGF3 binds to the promoter element of IFN-beta, positive regulatory domain I
      (PRDI), with significantly higher affinity than IRF-1, 2, and mutational analysis
      of PRDI showed that the gene expression and binding of ISGF3, but not of IRF-1,
      2, are highly correlated. Furthermore, our functional analysis involving a
      dominant negative inhibitor for ISGF3 activation and an anti-IFN neutralizing
      antibody clearly demonstrated the presence of a positive feedback path way for
      type I IFN genes mediated by ISGF3.

PMID- 8864861
TI  - Complete sequence, subunit structure, and complexes with pancreatic alpha-amylase
      of an alpha-amylase inhibitor from Phaseolus vulgaris white kidney beans.
AB  - The complete amino acid sequence of a white kidney bean (Phaseolus vulgaris)
      alpha-amylase inhibitor (PHA-I), which is composed of two kinds of
      glycopolypeptide subunits, alpha and beta, was established by conventional
      methods. The polypeptide molecular weight of PHA-I determined by the light
      scattering technique, considered together with the sequence molecular weights
      revealed for the subunits, indicated that PHA-I has the subunit stoichiometry of
      (alpha beta)2 complex. Inhibition test of PHA-I with increasing amounts of
      porcine pancreatic alpha-amylase (PPA) suggested that an inactive 2:1 complex is
      formed between PPA and PHA-I. In fact, two complexes differing from each other in
      the molar ratio of PPA to PHA-I were separated by gel filtration, and molecular
      weight estimation by the light-scattering technique confirmed that they are
      complexes of PHA-I with one or two PPA molecules. The binding of PPA to PHA-I
      appeared to follow simple binomial statistics, suggesting that two binding sites
      on PHA-I are independent and of high affinity for PPA.

PMID- 8864860
TI  - Cyclic AMP-dependent protein kinase but not protein kinase C regulates the
      cardiac Ca2+ channel through phosphorylation of its alpha 1 subunit.
AB  - The voltage-dependent L-type Ca2+ channel in the heart is regulated by cAMP
      dependent protein kinase (PKA) and possibly by protein kinase C (PKC). We have
      investigated the channel modulation through phosphorylation by these protein
      kinases, using liposomes into which Ca2+ channels from bovine heart were
      reconstituted. Phosphorylation of the proteoliposomes with PKA increased the
      dihydropyridine-sensitive Ca2+ efflux from them by about 70%. PKA rapidly
      phosphorylated membrane proteins of 210 and 170 kDa. A dihydropyridine-class Ca2+
      channel blocker, [3H]azidopine, specifically photo-labeled a protein of 210 kDa,
      suggesting that the 210-kDa phosphoprotein might be the alpha 1 subunit of the
      Ca2+ channel. In contrast, phosphorylation of the proteoliposomes with PKC failed
      to modulate the Ca2+ efflux. Although PKC catalyzed the phosphorylation of
      membrane proteins of 150, 130, 95, 67, and 62 kDa, the 210- and 170-kDa proteins
      were not phosphorylated by this kinase. These results suggest that
      phosphorylation of the 210-kDa protein in the cardiac sarcolemma by PKA may be
      responsible for modulation of the channel function, whereas modulation of the
      channel by PKC, if it occurs, must be the result of an indirect mechanism, e.g.
      phosphorylation of a cytoplasmic protein or an associated channel polypeptide,
      that cannot function in the reconstituted system.

PMID- 8864862
TI  - An arginine-213 to glycine mutation in human extracellular-superoxide dismutase
      reduces susceptibility to trypsin-like proteinases.
AB  - Molecular genetic studies of extracellular-superoxide dismutase (EC-SOD) have
      shown that individuals with high serum EC-SOD content have a single base
      substitution generating the exchange of glycine for arginine-213 (R213G) in the
      heparin-binding domain of this enzyme [Sandstrom, J. et al. (1994) J. Biol. Chem.
      269, 19163-19166], which causes the impairment of its binding ability to
      endothelial cell surface [Adachi, T. et al. (1996) Biochem. J. 313, 235-239].
      Serum EC-SOD in healthy individuals without the above mutation is heterogeneous
      with regard to heparin affinity and consists of five fractions, forms (I) to (V),
      of which (IV) and (V) are the main fractions with high affinity for heparin
      [Adachi, T. et al. (1995) J. Biochem. 117, 586-590], whereas the major fraction
      in hemodialysis patients was serum EC-SOD form (I), which is thought to be the
      proteolytic truncated form. On the other hand, serum EC-SOD in both healthy
      individuals and hemodialysis patients with the R213G mutation consisted mainly of
      the high heparin-affinity type. This observation suggests that the susceptibility
      of EC-SOD to proteinases is reduced by the R213G mutation. The affinity of normal
      EC-SOD (n-EC-SOD) for heparin decreased by the treatment with trypsin,
      accompanied by a reduction in the molecular mass. The IC50 of trypsin for the
      heparin affinity of R213G mutant EC-SOD (m-EC-SOD) was 0.15 microgram/ml,
      fivefold that for n-EC-SOD. Heparin affinity of n-EC-SOD was again more
      susceptible to neutrophils than that of m-EC-SOD. These results suggested that m
      EC-SOD is more resistant to trypsin and neutrophil-release trypsin-like
      proteinases than n-EC-SOD, which causes the heparin affinity of serum EC-SOD to
      differ in individuals with and without the R213G mutation.

PMID- 8864863
TI  - Binding of myosin subfragment 1 to actin.
AB  - The dissociation constant for the binding of myosin subfragment 1 (S1) and
      chromatographed actin in the presence and absence of nucleotide was measured at
      various ionic strengths and various temperatures. The dissociation constant was
      of nM order in the absence of nucleotide and increased by approximately 100- and
      approximately 100,000-fold in the presence of ADP and ATP, respectively. The
      dissociation constant also increased with increasing ionic strength, irrespective
      of the presence of nucleotide, and its dependence on the ionic strength was
      increased by the presence of ATP but decreased by the presence of ADP. The
      standard enthalpy change and entropy change for the binding of S1 to actin were
      both positive, irrespective of the presence of nucleotide, indicating that the
      binding was entropy-driven. The standard entropy change was essentially
      unaffected by the presence of ADP but was greatly decreased by ATP, suggesting
      that the large increase in the dissociation constant in the presence of ATP was
      due to the decrease of hydrophobic interactions. On the other hand, the increase
      in the dissociation constant for acto-S1 in the presence of ADP might be induced
      by the decrease of electrostatic interactions.

PMID- 8864864
TI  - Formation of the functional complexes of m2 muscarinic acetylcholine receptors
      with GTP-binding regulatory proteins in solution.
AB  - Sixteen different detergents were studied for solubilization of functional
      complexes between m2 muscarinic acetylcholine receptors (mAChR) and guanine
      nucleotide-binding regulatory proteins (G proteins). More than 40% of solubilized
      mAChR retained their GTP-dependent high affinity for agonist binding after
      solubilization with sucrose monolaurate, whereas all other detergents studied
      gave considerably lower solubilization yields or caused the loss of the high
      affinity for agonist binding. The preformation of mAChR-G protein complexes in
      membranes revealed that a large excess of G proteins did not increase the portion
      of high-affinity binding sites, but caused GTP- and Mg2(+)-dependent inhibition
      of the binding of radioactive antagonists to mAChR. The optimization of detergent
      concentration and other experimental conditions revealed that up to 47% of the
      solubilized receptors indicated the GTP-dependent high affinity for agonist
      binding after mixing solubilized mAChR with purified G proteins in sucrose
      monolaurate in the presence of Mg2+ and carbachol. These results give the first
      clear proof of the formation of functional complexes between mAChR and G proteins
      in solution and indicate that GTP-dependent high-affinity agonist binding is
      connected to the direct interactions between mAChR and G proteins and that other
      membrane components are not necessary.

PMID- 8864866
TI  - Medical devices: factors adversely affecting innovation.

PMID- 8864865
TI  - Structure of the gene encoding the human differentiation-stimulating
      factor/leukemia inhibitory factor receptor.
AB  - The human gene encoding the differentiation-stimulating factor (D
      factor)/leukemia inhibitory factor (LIF) receptor was cloned and its structure
      was analyzed. The gene spans more than 70 kilobases and contains 20 exons. The D
      factor/LIF receptor can be subdivided into several regions; cytokine receptor
      homologous domain 1, an Ig-like domain, cytokine receptor homologous domain 2,
      three fibronectin type III domains, a transmembrane domain and a cytoplasmic
      region. Each domain of the receptor is encoded by a set of exons. There is a TATA
      sequence upstream of the transcription initiation site. One unit of the Alu
      sequence is present in the 5' flanking region. An NF-IL6 site is located 31 bases
      downstream of the transcription initiation site.

PMID- 8864867
TI  - Activation of osteoclast-mediated bone resorption by the supernatant from a
      rabbit synovial cell line in response to polyethylene particles.
AB  - It is unknown whether the soluble factors produced from cells activated by wear
      particles in the fibrous tissue around failed joint prostheses really activate
      osteoclastic bone resorption. In this study, the activation of osteoclast
      mediated bone resorption by the products from a rabbit synovial cell line (HIG
      82) stimulated by various particles was investigated using rabbit unfractionated
      bone cells cultured on a dentin slice. The HIG cells were challenged with the
      following laboratory-made particles: high-density polyethylene (PE), cobalt alloy
      (Co-Cr), titanium alloy (Ti6Al4V), pure titanium (Ti), and sintered
      hydroxyapatite (HA). The size of each particle was < 2 microns. The supernatants
      from HIG cells cultured with the appropriate concentration of wear particles were
      added to unfractionated bone cells on a dentin slice, and then resorbed areas
      were determined for each particle. Interestingly, resorbed areas significantly
      increased only when the culture medium from HIG cells with PE particles was added
      to unfractionated bone cells. This study demonstrates that PE particles stimulate
      the rabbit synovial cells to produce soluble factors that induce osteoclast
      mediated bone resorption. Moreover, this experimental model is a useful method
      sensitively to evaluate the effects of soluble factors from the cells stimulated
      by particulate biomaterials from joint prostheses on osteoclastic bone
      resorption.

PMID- 8864868
TI  - Surface adsorption and fibrinogen interactions with hirudin-thrombin complex.
AB  - This study describes the protein interaction properties of hirudin-thrombin
      complex adsorbed onto a surface. Hirudin-thrombin complex, preadsorbed thrombin
      bound with hirudin, and thrombin were coated onto the surfaces of glass beads.
      The activity of the thrombin component adsorbed onto the surface, and hence the
      ability of hirudin to bind and inactivate thrombin, was determined by measuring
      the activity of thrombin to cleave fibrinogen to generate fibrin and to cleave a
      chromogenic substrate, S-2238. Pure thrombin adsorbed on the surface (without
      hirudin) retained its activity to cleave fibrinogen and cleave S-2238. Hirudin
      thrombin complex adsorbed on the surface did not stimulate the activation of
      fibrinogen, nor did it cleave S-2238.

PMID- 8864869
TI  - Experimental study of the antithrombogenic behavior of Dacron vascular grafts
      coated with hydrophilic acrylic copolymers bearing salicylic acid residues.
AB  - The objective of the present work was study of the behavior of active coatings of
      hydrophilic acrylic polymers bearing salicylic acid residues linked covalently to
      the macromolecular chains, after their application to woven and knitted Dacron
      vascular grafts. In vitro tests were carried out under dynamic flow conditions
      using equipment especially designed to reproduce physiologic conditions, to
      determine the retention of the coating using a saline solution. Ex vivo tests
      were carried out in an extracorporeal circuit using the dog as an animal model.
      The study of the deposition of platelets was followed by labeling of autologous
      platelets with 111In-oxine, as well as by analysis of the surfaces of the
      prostheses by scanning electron microscopy. An application of thin coatings of
      hydrophilic acrylic copolymers improves the antithrombogenicity of the vascular
      grafts with respect to the uncoated prosthesis. The presence of relatively small
      amounts of units bearing salicylic acid residues in the copolymer chains (5-20 wt
      %) gives good results when they are applied to woven and knitten Dacron meshes
      which have been quantified by analysis of the percentage of radiotracer on the
      surface of the vascular grafts tested in ex vivo experiments. The salicylic acid
      residues are released slowly to the medium by hydrolysis of the reversible
      covalent bonds of this compound to the acrylic macromolecular chains, which
      provides an additional antiaggregating effect for platelets. The polymeric
      coating forms a thin active film which improves the antithrombogenic properties
      of the surface of woven or knitted Dacron vascular grafts in ex vivo experiments.

PMID- 8864870
TI  - Material-induced up-regulation of leukocyte CD11b during whole blood contact:
      material differences and a role for complement.
AB  - Material-induced thrombogenicity is in part a consequence of leukocyte
      activation. To evaluate and compare material-induced platelet damage, we have
      expanded our in vitro flow cytometric immunoassay to include assessment of
      leukocyte activation. We have used a very simple system whereby fresh,
      heparinized whole blood contacts materials for 1 h at 37 degrees C under low
      shear. Unlike other tests that focus on adherent leukocytes, this assay evaluates
      the leukocytes in the whole blood drained from the tube (1.57 mm internal
      diameter, 25 cm length) after material contact. We demonstrate that whole blood
      contact with a polyvinyl alcohol (PVA) hydrogel surface leads to a twofold up
      regulation in CD11b surface expression of all monocytes and neutrophils. The
      activation is metal-ion dependent and highly material dependent in that blood
      contact with polyethylene and Silastic surface leads to minimal activation. The
      shedding of L-selection as a marker of leukocyte activation was found to be
      unsuitable in our assay given it ease of shedding in resting heparinized whole
      blood. Further, plasma levels of complement components Bb and sC5b-9 (ELISA
      assays) were significantly elevated only after blood contact with PVA hydrogel
      surfaces (9.4 micrograms/mL sC5b-9 and 9.6 micrograms/mL Bb). Use of recombinant
      soluble human CR1 (sCR1) to inhibit the action of the C3 and C5 convertases
      completely inhibited sC5b-9 levels in whole blood after contact with PVA hydrogel
      surfaces and inhibited CD11b up-regulation by over 70%, suggesting that material
      induced leukocyte activation is partially mediated by C5a production.

PMID- 8864871
TI  - Carcinogenicity of CoCrMo (F-75) implants in the rat.
AB  - A long-term study was conducted in rats to assess the contribution of the surface
      area of CoCrMo devices to carcinogenesis. Groups consisting of 104 rats each (52
      male, 52 female) were either implanted with metal cylinders fixed on the left,
      lateral femur (groups 1-3) or injected with a suspension of metal microspheres in
      the dorsal subcutis (group 4). Group 1 (control) received solid Ti6Al4V cylinders
      [surface area to body weight (SA/BW) ratio measuring 1.35 times that of human
      total hip prosthesis (HTHP)]. Group 2 was implanted with solid CoCrMo (SA/BW
      ratio: identical to implants of group 1). Group 3 received sintered-porous CoCrMo
      devices (SA/BW ratio: 30 x HTHP). Group 4 was injected with a suspension of
      CoCrMO microspheres (SA/BW ratio: 135 x HTHP). Implant-associated tumors (IATs)
      were observed in 23, 14, 3, and 15 rats of groups 1, 2, 3, and 4, respectively.
      Within groups 1 and 2, 34 IATs were associated with loose implants, three with
      undetermined implant fixation status, and none with fixed implants. A
      significantly increased accumulation of chronic inflammatory tissues around loose
      rather than fixed implants suggested a foreign-body reaction as the primary
      mechanism of carcinogenesis. A secondary role in carcinogenesis was ascribed to
      the increased CoCrMo implant SA/BW ratios as indicated by a 14.6% IAT incidence
      in group 4 versus 3% in group 3. These results support the notion that early
      intervention in the removal of loose metal devices is warranted to mitigate
      against foreign body-induced carcinogenesis, at least in this animal model.

PMID- 8864872
TI  - Surface chemical structure for soft contact lenses as a function of polymer
      processing.
AB  - The surface chemistry and topography of cast-molded Etafilcon-A and doubled-sided
      lathed Etafilcon-A soft contact lenses were determined to be significantly
      different. The variations in surface chemical and morphologic structure between
      the two lenses were the result of contact lens manufacturing methods. The surface
      of the cast-molded Etafilcon-A had a consistently less rough surface compared to
      the doubled sided lathed Etafilcon-A as determined by atomic force microscopy.
      The surface of the doubled sided lathed Etafilcon-A contained primarily silicone
      and wax contamination in addition to minute amounts of HEMA. The cast-molded
      Etafilcon-A had an elemental and chemical content which was consistent with the
      polymer stoichiometry. Contact angle wettability profiles revealed inherent
      wettability differences between the two lenses types. The cast-molded Etafilcon-A
      had an inherently greater water wettability, polarity, and critical surface
      tension. This means that these two lenses cannot be compared as similar or
      identical lens materials in terms of surface composition. The manufacturing
      method used to produce a soft contact lens directly determines the surface
      elemental and chemical structure as well as the morphology of the finished lens
      material. These results suggest possible differences in the clinical comfort,
      spoilage, and lubricity felt during patient wear.

PMID- 8864873
TI  - Surface roughness modulates the local production of growth factors and cytokines
      by osteoblast-like MG-63 cells.
AB  - Titanium (Ti) surface roughness affects proliferation, differentiation, and
      matrix production of MG-63 osteoblast-like cells. Cytokines and growth factors
      produced in the milieu surrounding an implant may also be influenced by its
      surface, thereby modulating the healing process. This study examined the effect
      of surface roughness on the production of two factors known to have potent
      effects on bone, prostaglandin E2 (PGE2) and transforming growth factor beta 1
      (TGF-beta 1). MG-63 cells were cultured on Ti disks of varying roughness. The
      surfaces were ranked from smoothest to roughest: electropolished (EP), pretreated
      with hydrofluoric acid-nitric acid (PT), fine sand-blasted, etched with HCl and
      H2SO4, and washed (EA), coarse sand-blasted, etched with HCl and H2SO4, and
      washed (CA), and Ti plasma-sprayed (TPS). Cells were cultured in 24-well
      polystyrene (plastic) dishes as controls and to determine when confluence was
      achieved. Media were collected and cell number determined 24 h postconfluence.
      PGE2 and TGF-beta 1 levels in the conditioned media were determined using
      commercial radioimmunoassay and enzyme-linked immunosorbent assay kits,
      respectively. There was an inverse relationship between cell number and Ti
      surface roughness. Total PGE2 content in the media of cultures grown on the three
      roughest surfaces (FA, CA, and TPS) was significantly increased 1.5-4.0 times
      over that found in media of cultures grown on plastic or smooth surfaces. When
      PGE2 production was expressed per cell number, CA and TPS cultures exhibited six-
      to eightfold increases compared to cultures on plastic and smooth surfaces. There
      was a direct relationship between TGF-beta 1 production and surface roughness,
      both in terms of total TGF-beta 1 per culture and when normalized for cell
      number. TGF-beta 1 production on rough surfaces (CA and TPS) was three to five
      times higher than on plastic. These studies indicate that substrate surface
      roughness affects cytokine and growth factor production by MG-63 cells,
      suggesting that surface roughness may modulate the activity of cells interacting
      with an implant, and thereby affect tissue healing and implant success.

PMID- 8864874
TI  - Platelet-polymer interactions: morphologic and intracellular free calcium studies
      of individual human platelets.
AB  - Light and electron microscopic methods were used to correlate changes in platelet
      morphology with levels of internal free calcium in platelets adhering to Formvar,
      Pellethane, and 14% SO3 Pellethane. Free calcium levels were elevated when
      platelets initially activated in response to contact with the polymer substrates.
      With buffer containing 1 mM CA2+, representative of in vivo plasma calcium
      levels, platelets activating on the sulfonated substrate exhibited significantly
      higher intracellular free calcium levels compared to those on Formvar and
      Pellethane. Furthermore, the intracellular free calcium remained elevated in
      these platelets which failed to spread normally on the sulfonated substrate. In
      contrast, the platelets adherent on Formvar and Pellethane achieved normal fully
      spread morphologies with correspondingly low or resting calcium levels. Our
      results indicate that the addition of the sulfonated group to Pellethane affected
      internal platelet calcium regulation to cause an abnormal spreading response. The
      nonviable platelet morphologies observed on sulfonated Pellethane compare to
      other dead cell morphologies caused by abnormally elevated levels of
      intracellular free Ca2+.

PMID- 8864875
TI  - Initial hemocompatibility studies of titanium and zirconium alloys: prekallikrein
      activation, fibrinogen adsorption, and their correlation with surface
      electrochemical properties.
AB  - Two novel metal alloys, Ti-13Nb-13Zr and Zr-2.5Nb, have been engineered for
      applications in orthopedic implants because of their favorable mechanical
      properties, corrosion resistance, and compatibility with bone and tissue. These
      alloys also have the ability to form a hard, abrasion-resistant, ceramic surface
      layer upon oxidative heat treatment (diffusion hardening, DH). Previous studies
      have indicated that these and other ceramics cause limited hemolysis and exhibit
      remarkable structural integrity after extended exposure to physiological
      environments. Such observations suggest that DH Ti-13Nb-13Zr and ZrO2/Zr-2.5Nb
      could be used successfully as components in blood-contacting devices. Materials
      intended for such applications must possess properties that do not elicit adverse
      physiological responses, such as the initiation of the coagulation cascade or
      thrombus formation. In the present study measurements of prekallikrein
      activation, fibrinogen adsorption from diluted human plasma, and the strength of
      fibrinogen attachment as judged by residence-time experiments were performed to
      evaluate the potential hemocompatibility of these materials. The results of the
      prekallikrein activation and fibrinogen-retention studies correlated well with
      two electrochemical properties of the alloys, the open circuit potential and
      reciprocal polarization resistance. The results indicate that both the original
      and treated Ti and Zr alloys activate prekallikrein and adsorb as well as retain
      fibrinogen in amounts similar to other materials used as components of blood
      contacting devices. On the basis of these studies, these alloys appear to be
      promising candidates for cardiovascular applications and merit further
      investigation.

PMID- 8864876
TI  - Deposition of collagen fibril bundles by long-term culture of fibroblasts in a
      collagen sponge.
AB  - Human fibroblasts cultured for 10 days in a collagen sponge migrated through the
      pores of the sponge and expressed a moderate mitotic activity, which stabilized
      after 10 days, and a high collagen and protein synthesis. Between 10 and 27 days,
      the newly synthesized collagen filled the pores of the sponge. This matrix
      accumulation induced a delayed decrease of collagen and protein synthesis.
      Finally, after 27 days of culture, the fibroblasts expressed low biosynthetic
      activities similar to the ones exhibited in vivo. The newly synthesized matrix
      was highly differentiated, as shown by the presence of a dense network of quarter
      staggered collagen fibrils (42 nm +/- 6 nm in diameter) surrounding the cells.
      The size and the shape of these fibrils demonstrated that the newly synthesized
      procollagen was fully processed in collagen by removal of their N- and C-terminal
      propeptides. Moreover, these fibrils were packed in bundles organized into an
      interwoven network that mimics the pattern of the papillary dermis. These
      findings show that fibroblasts cultured for one month in a collagen sponge
      construct large amounts of a highly differentiated connective tissue.

PMID- 8864877
TI  - In vitro properties of a chitosan-bonded bone-filling paste: studies on
      solubility of calcium phosphate compounds.
AB  - The present study investigated properties of various mixtures of organic acids
      (malic and malonic) and calcium phosphate compounds (beta-tricalcium phosphate,
      ashed bovine bone, and synthetic hydroxyapatite) with the objective of
      determining the optimum combination of organic acid and calcium phosphate
      compound for components of a chitosan-bonded bone-filling paste. beta-tricalcium
      phosphate was decomposed by malic acid and malonic acid, but these two acids did
      not decompose synthetic hydroxyapatite and ashed bovine bone. Assessment of ion
      release from a set paste containing either synthetic hydroxyapatite or ashed
      bovine bone indicated that only calcium ions were appreciably released after
      storing and stirring the set paste in physiologic saline for 7 days.

PMID- 8864878
TI  - Complement-mediated leukocyte adhesion on poly(etherurethane ureas) under shear
      stress in vitro.
AB  - Blood-contacting biomaterials may activate the complement cascade, thus promoting
      leukocyte adhesion to the biomaterial surface. We hypothesize that the extent of
      complement activation is modulated by biomaterial formulation and the presence of
      fluid shear stress. To investigate this hypothesis, we tested base
      poly(etherurethane ureas) formulated with or without Santowhite antioxidant, a
      nucleophilic additive. We found that adherent leukocyte densities decreased with
      increasing shear stress. Moreover, leukocyte adhesion was decreased significantly
      further by Santowhite additive under shear stress but not under static
      conditions. Monocytes showed a higher propensity for adhesion than did
      neutrophils under shear and static conditions. Under static conditions, adherent
      cells on the Santowhite-containing polyurethane had a slightly more activated
      morphology than those on the base polyurethane. Cell adhesion under shear stress
      was significantly decreased when C3 or fibronectin was depleted from the
      suspension medium. Santowhite additive increased Factor B adsorption to the test
      surface while shear stress increased Factor H adsorption. The combination of
      Santowhite additive and shear stress increased the adsorption of both Factor B
      and Factor H and the serum protein S-terminal complement complex levels, but it
      did not further increase the state of activation of adherent cells. We conclude
      that leukocyte adhesion on poly(etherurethane urea) surfaces is sensitive to the
      levels of shear stress and that both C3 and fibronectin are required to maintain
      adhesion in the presence of shear stress. The low state of cellular activation
      and increased Factor H adsorption may explain the decreased adherent leukocyte
      density on the Santowhite-containing polyurethane.

PMID- 8864879
TI  - Surface-induced mineralization: a new method for producing calcium phosphate
      coatings.
AB  - Calcium phosphate coatings were nucleated and grown from aqueous solution onto
      titanium metal substrates via surface-induced mineralization (SIM) processing
      techniques. This process is based on the observation that in nature organisms use
      biopolymers to produce ceramic composites, such as teeth, bones, and shells. The
      SIM process involves modification of a surface to introduce surface
      functionalization followed by immersion in aqueous supersaturated calcium
      phosphate solutions. This low-temperature process (< 100 degrees C) has
      advantages over conventional methods of calcium phosphate deposition in that
      uniform coatings are produced onto complex-shaped and/or microporous samples.
      Additionally, because it is a low-temperature process, control of the phase and
      crystallinity of the deposited material can be maintained.

PMID- 8864880
TI  - Crystallization of experimental bioactive glass compositions.
AB  - Crystallization kinetics studies for six experimental glass formulations in the
      system Na2O-CaO-SiO2-P2O5 synthesized by wet chemistry were conducted by means of
      differential thermal analysis. These glasses had CaO/P2O5 and SiO2/ (CaO + Na2O)
      ratios ranging from 8.74-3.38 and 0.92-3.03, respectively. Samples of each glass
      (n = 30 were heated from 23 to 1250 degrees C under N2 atmosphere at heating
      rates ranging from 10 to 50 degrees C/min. Glass-ceramics were obtained after
      heat treating the initial glasses at temperatures determined from their DTA
      exotherms. The activation energy of crystallization for each glass composition
      was calculated from an expression-relating log-heating rate and the reciprocal of
      the exothermic peak temperature. The compositions of the six glasses were
      significantly different (p = 0.05). The activation energy of crystallization (Q)
      values ranged from 196 to 782 kJ/mole. A correlation was obtained between Q and
      CaO/P2O5 and between Q and the Young's modulus (P < 0.001). Two of the six
      glasses exhibited bulk crystallization. X-ray diffraction studies showed that
      four of the six glasses exhibited different proportions of crystalline phases
      following heat treatment. These phases were wollastonite (CaSiO3), Na2CaSi3O9,
      combeite [Na4Ca3SI6O16(OH)2], and some unidentifiable phases. Two of the six
      bioceramic materials had a mixture of unknown crystalline phases.

PMID- 8864881
TI  - A method for determination of the anisotropic properties of biomembranes.
AB  - A methodology was developed for potential determination of the anisotropic
      properties of biomembranes. This method is based on the theoretical
      discretization of a continuous membrane used for finite element analysis and the
      simultaneous measurement of the displacement of nodes on the surface of a
      membrane. From the given loads and measured nodal displacements, one can assemble
      the resulting stiffness matrix and approximate the material properties associated
      with the membrane. Mathematical estimations and computer simulations were
      performed to determine the perturbation of load and displacement errors on the
      resulting material properties. The results indicated that the material properties
      are particularly sensitive to displacement errors. The displacement measurements
      may require an accuracy of 20 microns for a 4 x 4 cm2 specimen. Significant
      inaccuracies occur close to the points of load application.

PMID- 8864882
TI  - Human monocyte morphology is affected by local substrate charge heterogeneity.
AB  - Cells are sensitive to topological, chemical, and electrical properties of
      substrates on which they are grown. However, most studies of cell-surface
      interactions have neglected electrical effects or confounded them with other
      substrate properties. The use of nanofabrication technology has made it possible
      to fabricate optically transparent surfaces with controlled chemistry and
      topology, and with active, controllable surface charge density in domains as
      small as 1-4 microns. Human monocytes incubated on polystyrene with 3.3 microns
      wide strip domains, alternately charged so as to maintain overall charge
      neutrality, show significant charge density and time-dependent increases (greater
      than twofold) in cell area and cell perimeter after challenge with a phagocytic
      trigger (human IgG opsonized zymosan particles). Additional utlrastructural
      studies on silicon dioxide substrates show charge-density-dependent qualitative
      morphological differences. These studies clearly demonstrate that human monocytes
      respond in vitro to local surface-charge heterogeneity in the absence of
      substrate topology and compositional variation.

PMID- 8864883
TI  - Evaluation of factors affecting bonding rate of calcium phosphate ceramic
      coatings for in vivo strain gauge attachment.
AB  - The aim of this study was to compare the bone-bonding rates of eight calcium
      phosphate ceramic (CPC) coatings attached to strain gauges, alone and in
      conjunction with an OP1 device (Creative BioMolecules, Hopkinton, MA) and
      autologous concentrated pericyte cells. These coatings were studied to develop
      faster bone bonding to long-term in vivo strain sensors. Characterization of the
      CPC powders using electron microscopy and X-ray diffraction showed that they had
      shapes ranging from spherical to rocklike and properties ranging from highly
      crystalline to amorphous. CPC coated gauges were placed on the femora of young
      male dogs during aseptic surgery and were initially held in place using
      resorbable sutures. Test groups were euthanized after 3, 9, and 12 weeks. Both
      femora of the dogs were explanted and cantilever loaded. Response of the
      implanted hydroxyapatite (HA) coated gauges were compared to the response of
      bench-top glued sets of gauges (controls) attached to the contralateral femur and
      reported as a percentage of the control values. One CPC coating type showed an
      average response of 30% of controls after 3 weeks, four showed average responses
      higher than 75% after 9 weeks, and three showed averages higher than 82% after 12
      weeks in vivo. Amorphous CPC coatings bonded more quickly than crystalline ones
      and particle shape had less effect than crystal structure on bonding rates. When
      either OP1 or autologous concentrated pericyte cells were placed on selected CPC
      coated gauge surfaces, the CPC5 coated gauges bonded best after 3 weeks with a
      response of 59%. After the same time period in vivo, CPC3 and CPC7 provided
      responses of 40 and 16%, respectively. Comparison of a soluble calcium-coated CPC
      with an uncoated one that had identical crystal structure and similar particle
      shape indicated that the calcium coating slowed bone bonding substantially in the
      young dog model. Optical microscopy of stained undecalcified bone sections and
      backscattered electron imaging indicated bone formation at all bone-HA interfaces
      and an increase in the number of areas of bone remodeling adjacent to the gauge
      at all time periods. Gross bone remodeling due to strain gauge placement was only
      observed near the distalmost cell-seeded strain gauges. Selection of the type of
      coating and enhancement system can accelerate bone bonding to strain sensors but
      must be tailored to the bone of the model in which it is being used. Augmentation
      of CPC coatings with cells or OP1 resulted in variable enhancement of the bonding
      rate and depended on the CPC and the enhancement system.

PMID- 8864884
TI  - Testing of bone-biomaterial interfacial bonding strength: a comparison of
      different techniques.

PMID- 8864885
TI  - A self-setting TTCP-DCPD apatite cement for release of vancomycin.
AB  - Vancomycin (VCM), a methiciline-cefem resistant Staphylococcus aureus (MRSA)
      specific antibiotic, was incorporated in a self-setting tetracalcium phosphate
      (TTCP)-dicalcium phosphate dihydrate (DCPD) apatite cement that hardened
      isothermally into a hydroxyapatite (HAP) phase with crystallinity similar to that
      of host bone. Effective release of VCM into PBS lasted for 2 weeks from cements
      containing 1% VCM and for longer than 9 weeks from cements containing 5% VCM. The
      rate of release of VCM differed between cements with different crystallinities as
      well as between the two dissolution media, PBS and simulated body fluid. Mean
      concentration of VCM in the bone marrow tissue released from cements containing
      5% VCM was 20 times the minimum inhibitory concentration 3 weeks after
      implantation in bone. Direct contact with new bone was observed with the cements
      containing 1% VCM. Slow delivery of VCM from a self-setting TTCP-DCPD apatite
      cement with low crystallinity could be used to treat MRSA osteomyelitis.

PMID- 8864886
TI  - Apatite formation on silica gel in simulated body fluid: its dependence on
      structures of silica gels prepared in different media.
AB  - It has been shown that the prerequisite for glasses and glass-ceramics to bond to
      living bone is the formation of a layer of biologically active bonelike apatite
      on their surfaces. The hydrated silica formed on the surfaces of glasses and
      glass-ceramics plays an important role in nucleating the apatite. In the present
      study, the structure of the hydrated silica responsible for the apatite
      nucleation was investigated in an accellular simulated body fluid with ion
      concentrations nearly equal to those of human blood plasma. Three kinds of porous
      silica gels were prepared by hydrolysis and polycondensation of tetraethoxysilane
      in pure water or in aqueous solution containing polyethylene glycol or
      polyacrylic acid. The silica gels prepared in aqueous solution containing
      polyethylene glycol or polyacrylic acid had micron-size interconnected pores,
      whereas the gel prepared in pure water did not. All the gels contained a large
      volume of nanometer-size pores, almost the same amounts of silanol groups and D2
      defect, and showed a high dissolution rate of the silica. Despite this, only the
      gel prepared in the solution containing polyethylene glycol formed the apatite on
      its surface in the simulated body fluid. This indicates that only a certain type
      of structural unit of the silanol group is responsible for the apatite
      nucleation.

PMID- 8864887
TI  - Different effects of phagocytosable particles during bone formation versus
      remodeling.
AB  - Previously, small phagocytosable particles of high density polyethylene (HDPE)
      but not Ti6-Al4-V alloy, at a concentration of 10(8) particles/mL inhibited net
      bone formation in vivo after 3 weeks in the bone harvest chamber (BHC). These
      findings reflected the effects of particles during the phase of bone ingrowth. In
      this study, we tested whether these effects persisted or were different during
      the phase of bone maturation and remodeling. BHCs were bilaterally implanted in
      mature male NZW rabbits. After a 6-week period for osseointegration, the contents
      of the chamber were harvested and discarded. One percent sodium hyaluronate, the
      carrier, was then placed within the canal of the chambers bilaterally and the
      tissue within the chambers was harvested 3 weeks later. HDPE particles were then
      inserted unilaterally for a 3-week period, followed by Ti6-Al4-V for 3 weeks,
      HDPE for 6 weeks, and Ti6-Al4-V for 6 weeks. The side chosen for each treatment
      was switched consecutively; the nonimplanted, contralateral chamber served as a
      control. At 3 weeks the control treatments yielded trabeculae of woven bone in a
      fibrovascular stroma. By 6 weeks, the peripheral trabeculae were thicker, and a
      central marrow cavity was developing. Bone ingrowth was less with HDPE particles
      at 3 and 6 weeks compared to controls. Ti6-Al4-V particles did not inhibit bone
      ingrowth at 3 weeks but showed a trend at 6 weeks. The characteristics of
      particles affect the differentiation, maturation, and remodeling of mesenchymal
      tissue differently.

PMID- 8864888
TI  - Wear testing of materials and surfaces for total knee replacement.
AB  - A simple wear test was investigated for evaluating the wear and damage of
      material pairs when used in total knee replacement. The test consisted of an
      axially loaded metallic femoral indentor and a reciprocating ultrahigh molecular
      weight polyethylene (UHMWPE) flat disk that represented the tibial component. A
      number of variables were studied including the effect of conformity by varying
      the radii of the femoral surface, distilled water or serum as a lubricant,
      different femoral materials, and different types of UHMWPE. In general, the
      different morphologies of the surface wear of the UHMWPE were similar to those
      seen on retrieved total knee replacements. Increased conformity with a
      cylindrical indentor gave a reduced wear rate initially, compared with that of
      the lower conformity spherical indentor. However, the wear rates were similar
      subsequent to this initial wearing in phase. Transfer films of UHMWPE were
      observed on the cobalt-chrome indentors for both serum and distilled water
      lubrication, although this film was more extensive for distilled water. The
      lowest wear rate was observed when oxidized zirconium was used on the femoral
      side, which was attributed to greater wettability, surface hardness, and immunity
      to oxidative wear. Tests using cobalt-chrome femoral cylinders and different
      grades of UHMWPE showed different wear rates. Of these PEs, GUR 415 showed less
      wear than both RCH 1000 and UHMWPE containing numerous fusion defects. For the
      latter, wear was attributed to a fatigue mechanism, although in most cases it was
      associated with surface phenomena rather than subsurface cracking. However, in
      some specimens of UHMWPE subsurface crack propagations occurred with defects. The
      test method is discussed in relation to its applicability to the evaluation and
      comparison of bearing materials and surfaces, with particular application to
      total knee replacements.

PMID- 8864889
TI  - Studies on epoxy compound fixation.
AB  - Bioprostheses derived from collagenous tissues have to be fixed and subsequently
      sterilized before they can be implanted in humans. Clinically, the most commonly
      used fixative is glutaraldehyde. However, the tendency for glutaraldehyde to
      markedly alter tissue stiffness and promote tissue calcification are well
      recognized drawbacks of this fixative. To address the deficiencies with the
      glutaraldehyde-fixed tissue, a new fixative, epoxy compound, was used to fix
      biological prostheses. The study was undertaken to investigate the fixation rates
      and crosslinking densities of biological tissues fixed with various epoxy
      compounds. These epoxy compounds are different in their chemical structures.
      Glutaraldehyde was used as a control. The fixation rates and crosslinking
      densities of the fixed tissues were determined by measuring their fixation
      indices and denaturation temperatures, respectively. Generally, the epoxy-fixed
      tissues were more pliable than the glutaraldehyde-fixed one. Furthermore, the
      tissues fixed with monofunctional epoxy compound were more pliable than those
      fixed with multifunctional epoxy compounds. With increasing pH or temperature,
      the fixation rate of epoxy compound increased. However, the number of epoxide
      functional groups did not seem to affect the fixation rate of the epoxy compound.
      The fixation rate of glutaraldehyde was faster than that of epoxy compounds.
      Additionally, the crosslinking density of the glutaraldehyde-fixed tissue was
      greater than that of the epoxy-fixed counterparts. Moreover, it was noted that
      the denaturation temperatures of the tissues fixed with glutaraldehyde or
      multifunctional epoxy compounds were significantly higher than the fresh ones (p
      < 0.05), while that fixed with monofunctional epoxy compound stayed roughly the
      same throughout the entire fixation process (p > 0.05). The results obtained in
      this study may be used to optimize the fixation process for developing
      bioprostheses fixed with epoxy compounds.

PMID- 8864890
TI  - Knot performance of polypropylene sutures.
AB  - A mechanical performance test using an Instron Tensile Tester demonstrated the
      superior handling characteristics of Surgipro suture as compared to Prolene
      suture that facilitated knot construction without suture breakage. For both
      granny and square knots, the knot run down forces for the Surgipro sutures were
      significantly less than those encountered for comparable knots for Prolene
      sutures. This propensity of the two-throw knots of Surgipro sutures to advance
      without breakage considerably facilitated knot construction.

PMID- 8864891
TI  - Poly (2-hydroxyethyl methacrylate) particles for management of hemorrhage of
      complicated origin: treatment of hemobilia.
AB  - Poly (2-hydroxyethyl methacrylate) (PHEMA) particles of cylindrical and spherical
      shape were developed as a preparation for tumor treatment or control of
      hemorrhage by blocking their blood supply. In this report, PHEMA particles were
      used for the management of hemobilia, that is, bleeding into biliary passages.
      The origin of hemobilia in 31 patients was localized by selective angiography.
      With the objective of prophylaxy of hemorrhage, selective embolization with PHEMA
      particles of the branches of the hepatic artery responsible for the supply of
      blood to the focus of damage was used in 18 patients. This low-trauma method
      allowed either a complete control of bleeding or, at least, intraoperative blood
      loss was reduced more than twice. Histological investigation of the occluded
      blood vessels showed that the thrombus was attached to the particles and was
      reinforced by the porous structure of the polymer. A hypercoagulation reaction
      was observed in the postembolization period. This allowed correction of the
      hypocoagulation in the hemostasis system.

PMID- 8864892
TI  - Regulatory concerns in the development of biologic-biomaterial combinations.
      United States Food and Drug Administration.
AB  - Several biologic-biomaterial combinations are currently under development in an
      attempt to modulate tissue or organ function in patients. The FDA regulations on
      combination products and the intercenter agreements among the Center for
      Biologics Evaluation and Research (CBER), the Center for Devices and Radiological
      Health (CDRH), and the Center for Drugs Evaluation and Research (CDER) provide
      further guidance on center jurisdiction of combination products and other
      products where there are jurisdictional concerns. The biological component of
      biologic-biomaterial combinations raises a number of issues that relate to the
      safety and bioactivity of the final product. For example, transmission of
      adventitious agents to patients via somatic cells, tissue, or cell-derived
      products is a major safety concern as are in vivo inflammatory responses elicited
      by the biomaterial component. CBER has drafted a number of "Points to Consider"
      documents to provide further guidance in the development of biological products.
      The intent of this article is to provide the highlights of the FDA regulations
      for combination products and the intercenter agreement between CBER and CDRH
      delineating the responsibilities of each center for medical device activities. In
      addition, the article focuses on the CBER's concerns related to the development
      of somatic cell-biomaterial combinations for therapeutic use.

PMID- 8864893
TI  - Implications of increased bone density in osteoarthritis.

PMID- 8864894
TI  - Osteoarthritis in cynomolgus macaques. III: Effects of age, gender, and
      subchondral bone thickness on the severity of disease.
AB  - Knee joints from cynomolgus monkeys of both genders and a wide range of ages were
      examined to characterize further the natural history of osteoarthritis (OA) in
      these animals. The objectives of this study were to characterize better the
      subchondral bone changes previously noted in this disease, to determine whether
      the severity of OA in these animals is affected by age or weight, and to
      determine whether males and females are affected similarly. As had been seen in
      previous studies, the medial tibial plateau was the most severely affected site.
      The thickness of the subchondral plate in the medial tibial plateau increased
      with increasing severity of articular cartilage lesions in both males and
      females; however, in monkeys with subchondral plate thicknesses less than 400
      microns, articular cartilage lesions were essentially absent. Subchondral plate
      thickness increased with increasing weight in both genders, but females had a
      higher subchondral plate thickness than males for a given body weight. There was
      no correlation between bone volume in the proximal tibial epiphysis and articular
      cartilage lesions of OA. The prevalence and severity of OA in the medial tibial
      plateau increased with increasing age, but were not affected by gender or weight.
      Although there was no correlation between articular cartilage lesions and body
      mass index or weight, the waist/hip circumference ratio and severity of articular
      cartilage lesions were correlated in the female monkeys. This work provides
      evidence that thickening of the subchondral bone plate may be more important than
      the volume of epiphyseal/metaphyseal cancellous bone in determining the
      biomechanical stresses in the joint and in influencing the development of
      articular cartilage lesions.

PMID- 8864895
TI  - Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related
      peptide by PTH in primary fetal rat osteoblasts.
AB  - We studied the effects of parathyroid hormone (PTH) on PTH parathyroid hormone
      related peptide (PTHrP) receptor mRNA level, PTHrP binding and PTH-stimulated
      cyclic adenosine monophosphate (cAMP) accumulation in osteoblasts, derived from
      fetal rat calvariae (ROB). Cells isolated during 10-70 minutes of collagenase
      treatment were seeded at a density of 25,000 cells/cm2 and cultured for 4 days.
      These cells show a fast increase in cAMP production after stimulation for 5
      minutes with 20 nM bovine parathyroid hormone(1-34) (bPTH(1-34)). When ROB are
      incubated with bPTH(1-34) (0.04-40nM) for 24 h, a dose-dependent decrease of the
      PTH/PTHrP receptor mRNA level, PTHrP binding, and PTH-stimulated cAMP
      accumulation can be observed. Pretreatment of ROB with a high concentration of
      bPTH(1-34) (40 nM) leads within 15 minutes to a decrease in PTH-stimulated cAMP
      accumulation. However, it takes > or = 3 h before a significant decrease in
      PTH/PTHrP receptor mRNA level can be observed. Also a significant decrease in
      PTHrP binding is observed after only 4 h of incubation with bPTH(1-34). Compared
      with bPTH(1-34), pretreatment of ROB with bPTH(3-34) (40 and 100 nM) for 24 h
      causes smaller decreases in PTH-stimulated cAMP accumulation, PTHrP binding, and
      in the PTH/PTHrP receptor mRNA level. We investigated the possible involvement of
      the protein kinase A signaling pathway in the regulation of the PTH/PTHrP
      receptor mRNA expression. Both forskolin and (Bu)2cAMP decreased PTHrP binding
      and PTH/PTHrP mRNA levels. These observations suggest that chronic activation of
      the PKA signaling pathway may down-regulate PTH/PTHrP receptor expression and
      thus hormone responsiveness in "normal" osteoblasts. In short, we found that the
      decrease of the PTH-stimulated cAMP accumulation after long-term pretreatment
      with bPTH(1-34) is correlated with both PTH/PTHrP receptor mRNA level and PTHrP
      binding. These data also suggest that the initial desensitization (< 30 minutes)
      of PTH-stimulated cAMP responsiveness by pretreatment with a high concentration
      of bPTH(1-34) (40 nM) is not dependent on the number of available PTH/PTHrP
      receptors. The protein kinase A signaling pathway is involved in the regulation
      of the PTH/PTHrP receptor, but, regarding the effect of bPTH(3-34), other
      signaling systems are also involved.

PMID- 8864896
TI  - Hysteresis of the PTH-calcium curve during hypocalcemia in the dog: effect of the
      rate and linearity of calcium decrease and sequential episodes of hypocalcemia.
AB  - Several studies have shown the presence of hysteresis of the parathyroid hormone
      (PTH)-calcium relationship in both normal humans and hemodialysis patients; for
      hypocalcemia, hysteresis is defined as a lower PTH level for the same serum
      calcium during the recovery from than the induction of hypocalcemia. However,
      some have questioned whether hysteresis is only a function of the rate and/or
      direction of change in calcium, and others have proposed that hysteresis is due
      to depletion of PTH stores. To address these issues, two groups of dogs were
      studied. To induce hypocalcemia, sodium EDTA (50 mg/kg) was infused either over
      60 (termed slow) or 30 (termed fast) minutes; immediately after the cessation of
      the ethylenediamine tetracetate (EDTA) infusion, calcium chloride (0.75 mEq/kg)
      was infused over 60 or 30 minutes, respectively, to correct the hypocalcemia. The
      EDTA infusion produced a linear decrease in serum calcium by progressively
      increasing the infusion rate at regular intervals. A second cycle of hypocalcemia
      and recovery using the same protocol was started immediately after the completion
      of the first cycle. To determine whether a nonlinear decrease in the serum
      calcium affected the PTH response to hypocalcemia, a third group of dogs, termed
      superfast, was studied; in this group, EDTA was infused for 30 minutes at a
      constant rate of 50 mg/kg. The hysteretic loops of PTH produced by the two
      sequential slow and fast cycles and the superfast cycle during the induction of
      and recovery from hypocalcemia were similar. Moreover, the maximal PTH level for
      the two sequential slow and fast cycles and the superfast cycle was not different
      even though the rates of calcium decrease varied and the calcium decrease was
      nonlinear in the superfast cycle. In conclusion, (1) since hysteresis was
      reproducible and the maximal PTH was not different during two sequential cycles
      of hypocalcemia, hysteresis is not due to PTH depletion; (2) the PTH-calcium
      curve is not affected by the rate at which hypocalcemia is induced; and (3) the
      maximal PTH level is not influenced by either the rate or linearity of the
      reduction in serum calcium.

PMID- 8864897
TI  - Abnormal modulation of serum osteocalcin by dietary phosphate and 1,25
      dihydroxyvitamin D3 in the hypophosphatemic mouse.
AB  - We evaluated in normal and hypophosphatemic (Hyp) mice whether changes in serum
      levels of osteocalcin in response to dietary phosphate supplementation,
      parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)
      administration were related to perturbations in calcium phosphate homeostasis. In
      normal mice, serum osteocalcin levels were not altered by phosphate
      supplementation. In contrast, phosphate supplementation in Hyp mice led to a 2
      fold decrease in serum osteocalcin to normal levels after 3 days and to an
      increase in osteocalcin levels after 14 days. The decrease in osteocalcin was
      associated with normophosphatemia, severe hypocalcemia, and marked increases in
      circulating 1,25(OH)2D3 levels, whereas the increase in osteocalcin levels was
      associated with normophosphatemia and no change in serum calcium and 1,25(OH)2D3.
      Administration of PTH decreased serum osteocalcin in both genotypes. Infusion of
      1,25(OH)2D3 for 3 days elicited increases in serum osteocalcin and calcium levels
      in normal mice, whereas in Hyp mice it produced significant decreases in
      osteocalcin levels and no change in serum calcium. However, with a more prolonged
      infusion of 1,25(OH)2D3, hypercalcemia and increases in serum osteocalcin were
      induced in mutant mice. Our results suggest that the abnormal osteocalcin
      response of Hyp mice is not directly attributable to an osteoblast dysfunction
      but is secondary, at least in part, to perturbations in factors that modulate the
      osteoblast activity, especially serum calcium and/or PTH.

PMID- 8864898
TI  - A large-scale population-based study of the association of vitamin D receptor
      gene polymorphisms with bone mineral density.
AB  - Conflicting results have been reported on the association between restriction
      fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus
      (i.e., for BsmI, ApaI, and TaqI) and bone mineral density (BMD). We analyzed this
      association in a large population-based sample (n = 1782) of men and women aged
      55-80 years using a novel direct haplotyping polymerase chain reaction (PCR) test
      to monitor the three polymorphic sites simultaneously. The direct haplotyping
      test we developed demonstrated a larger degree of genetic polymorphism at the VDR
      gene locus than described until now. None of the individual RFLPs were associated
      with BMD at the proximal femur. By analyzing allele dose effects, we identified a
      VDR haplotype allele weakly associated with low BMD. This allele, as one
      representative of the group of b alleles, is different from the BsmI allele
      previously reported by other groups to be associated with low BMD. This suggests
      allelic heterogeneity at the VDR locus in relation to BMD. Our results indicate
      at most a small effect of the VDR genotype on BMD in this elderly population.
      Since anonymous polymorphisms were analyzed, alternative explanations for our
      results include linkage to another nearby bone-metabolism related gene.

PMID- 8864899
TI  - Anabolic effects of prostaglandins in cultured fetal rat calvariae: structure
      activity relations and signal transduction pathway.
AB  - The structure-activity relations and signal transduction pathways for the
      anabolic effects of prostaglandins were examined in cultured fetal rat calvariae.
      In the presence of cortisol prostaglandins of the E and F series (10(-9) to 10(
      5) M) produced a dose-related increase in [3H]thymidine incorporation up to 4
      fold at 24 h. Prostaglandin E2 (PGE2) was also effective in the absence of
      cortisol. Butaprost (10(-6) M), a selective EP-2 receptor agonist, produced
      partial stimulation. Prostaglandin D2, prostacyclin, sulprostone, an EP-1 and EP
      3 receptor agonist, and fluprostenol, an FP receptor agonist, were ineffective.
      Forskolin (10(-4) M) increased [3H]thymidine incorporation 3-fold, while phorbol
      myristate acetate (PMA) (10(-6) M) produced a 1.8-fold increase.
      Isobutylmethylxanthine (IBMX) increased [3H]thymidine incorporation in control
      cultures, in the absence of cortisol, and increased the response to PGE2 in
      control and cortisol-treated cultures. [3H]proline incorporation into collagen
      and noncollagen protein was measured in the continuous presence of prostaglandins
      and cortisol for 72-96 h (continuous model) or when prostaglandins and cortisol
      were applied for 24 h, followed by culture for 48 h in control medium (on/off
      model). The effects on collagen were greater than on noncollagen proteins, so
      that the percent of collagen synthesis increased. The effects of prostaglandins
      and forskolin paralleled their mitogenic effects. PMA increased only noncollagen
      protein. Indomethacin did not diminish the anabolic response, while aphidicolin
      produced only partial inhibition. We conclude that the anabolic effects of
      prostaglandins on replication and differentiation of osteoblasts are likely to be
      mediated by an EP-2 receptor that stimulates adenylate cyclase.

PMID- 8864900
TI  - Signal transduction by basic fibroblast growth factor in rat osteoblastic Py1a
      cells.
AB  - Basic fibroblast growth factor (bFGF) is a potent mitogen for bone. In this
      study, we utilized the clonal rat osteoblastic cell line, Py1a, to examine signal
      transduction by bFGF and to determine the role of mitogen activated protein
      kinases (MAPK) and induction of c-fos mRNA in the mitogenic response to bFGF.
      Stimulation of [3H]thymidine incorporation (TDR) into DNA by bFGF was determined
      in the presence of phorbol myristate acetate of (PMA) to down-regulate the
      protein kinase C (PKC) pathway, genistein, an inhibitor of tyrosine kinase and H
      7, a PKC inhibitor, bFGF 10(-8) M and PMA 10(-7) M increased TDR by 242 and 245%,
      respectively. Treatment with bFGF or PMA for 5 or 30 minutes increased tyrosine
      phosphorylation of multiple proteins, and immunoblotting with MAPK-specific
      antibody revealed that two of these bands were the 42 and 44 kD isoforms of MAPK.
      PMA and bFGF induced c-fos mRNA expression at 30 minutes. Genistein at 10
      micrograms/ml blocked the mitogenic effect of bFGF and partially inhibited the
      mitogenic effect of PMA. Genistein at 100 micrograms/ml also blocked both bFGF-
      and PMA-induced increases in c-fos mRNA. A 24 h pretreatment with PMA at 10(-7) M
      inhibited the mitogenic response, tyrosine phosphorylation of MAPK, and induction
      of c-fos mRNA subsequent to the addition of PMA, but not bFGF. H-7 at 50 microM
      blocked bFGF-induced mitogenesis and c-fos induction, but did not inhibit bFGF
      induced tyrosine phosphorylation of MAPK. In this study, we show that the
      signaling pathway of bFGF and PMA are similar in that they both induce tyrosine
      phosphorylation of MAP kinases and activate c-fos. However, the signaling
      pathways ultimately diverge in that once the PKC pathway is down-regulated by PMA
      pretreatment or blocked by the PKC inhibitor H-7, tyrosine phosphorylation of MAP
      kinase, c-fos induction, and the mitogenic effect of PMA is blocked. In contrast,
      down-regulation of the PKC pathway inhibits c-fos and the mitogenic response to
      bFGF, but not bFGF's effects on tyrosine phosphorylation of MAP kinase.

PMID- 8864901
TI  - Osteochondrogenic potential of marrow mesenchymal progenitor cells exposed to TGF
      beta 1 or PDGF-BB as assayed in vivo and in vitro.
AB  - Mesenchymal progenitors cells can be isolated from rat bone marrow and
      mitotically expanded in vitro. When these cells, which we operationally call
      mesenchymal stem cells (MSCs), are placed in an appropriate environment, they
      have the capacity to differentiate into bone and/or cartilage. This capacity is
      called osteochondrogenic potential. In this study, preconfluent MSCs were exposed
      in vitro to 5 ng/ml transforming growth factor-beta 1 (TGF-beta 1) or platelet
      derived growth factor, isoform BB (PDGF-BB) for a pulse of 48 h and assayed for
      cell proliferation, alkaline phosphatase activity, and osteochondrogenic
      potential; untreated MSC's served as controls. In these cell culture conditions,
      TGF-beta 1 or PDGF-BB had similar effects on proliferation and alkaline
      phosphatase activity. Both growth factors increased cell proliferation and
      decreased alkaline phosphatase activity of MSCs. Sister cultures of TGF-beta 1-
      or PDGF-BB-treated MSCs and untreated MSCs were trypsinized. For each type of
      culture, the trypsinised MSCs were split in two parts: one part was replated in
      an osteogenic medium to assess its in vitro osteogenic potential, whereas the
      other part was seeded into porous calcium phosphate ceramics and implanted
      subcutaneously in syngeneic rats to assess its in vivo osteochondrogenic
      potential. PDGF-pretreated MSCs showed no difference in in vivo and in vitro
      osteochondrogenesis from that of control MSCs, while TGF-beta 1 pretreatment
      blocked the osteochondrogenic potential of MSCs when assayed in vitro for bone
      nodule formation. However, when tested in vivo, TGF-beta 1-pretreated MSCs were
      able to form bone and cartilage. These data show that measurements of
      proliferation and alkaline phosphatase activity of preconfluent MSCs immediately
      after exposure to growth factor were not predictive of their subsequent
      osteochondrogenic potential. Moreover, the variation of the osteochondrogenic
      potential of MSCs after exposure to growth factor was further modulated by the
      environment in which the MSCs were assayed.

PMID- 8864902
TI  - Ketoconazole and phorbol myristate acetate regulate osteoclast precursor fusion
      in primary murine marrow culture.
AB  - Osteoclast formation requires both precursor proliferation and then fusion into a
      multinuclear cell. These processes can be separated in primary murine marrow
      culture where osteoclastogenesis is stimulated by 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3). Here we investigate the regulation of precursor fusion.
      Ketoconazole, an agent known to inhibit cell fusion, added during the fusion
      period (days 5-6), dose-dependently inhibited formation of tartrate-resistant
      acid phosphatase+ (TRAP+) multinucleated cells (TRAP+MNCs), maximally at 62 +/-
      4% (n = 10). TRAP+MNCs in cultures exposed to 48 h of ketoconazole (1 microM)
      during fusion had fewer nuclei compared with control (11.7 +/- 0.6 vs. 15.1 +/-
      0.9). This inhibitory effect was completely reversed 24 h after removal of
      ketoconazole from culture. Phorbol myristate acetate (PMA) stimulated TRAP+MNC
      formation when given during the last 12 h of culture (2.3 +/- 0.2 fold compared
      with control). This increased formation was unaffected by the addition of
      hydroxyurea and accompanied by an increase in nuclei per TRAP+MNC (15.5 +/- 0.9
      vs. 13.1 +/- 0.6). Finally, staurosporine decreased TRAP+MNC formation in the
      presence or absence of PMA, implying that protein kinase C is involved in
      fusogenic processes. Regulation of fusion appears to be another mechanism by
      which bone remodeling can be modulated in vivo.

PMID- 8864903
TI  - DNA fragmentation during bone formation in neonatal rodents assessed by
      transferase-mediated end labeling.
AB  - To study the fate of bone cells, we used the transferase-mediated, biotin-dUTP
      nick end-labeling (TUNEL) assay to detect DNA fragmentation during the formation
      of intramembranous and endochondral bone in newly born hamsters, mice, and rats.
      In alveolar bone forming around the developing tooth crowns, DNA fragmentation
      was found in three cell types: TRAP-negative mononuclear cells at the bone
      surface, osteocytes, and some but not all nuclei of TRAP-positive osteoclasts.
      Osteoblasts did not undergo DNA fragmentation. A strong positive correlation was
      found between contacts of TUNEL-positive osteocytes and osteoclasts.
      Extracellular bone matrix also stained occasionally for the presence of DNA
      fragments. During endochondral bone formation, TUNEL staining was detected in
      late hypertrophic chondrocytes of the epiphyseal growth plate. During rapid
      longitudinal growth of long bones, TUNEL-positive hypertrophic chondrocytes were
      found coincident with or slightly after invasion of blood vessels from the
      diaphysis. However, during slow longitudinal growth and in secondary ossification
      centers, DNA fragmentation was seen in hypertrophic chondrocytes still located
      within their lacunae. We conclude that some of the osteocytes in deeper layers of
      bone die within their lacuna and disperse nuclear fragments over the
      extracellular matrix, that a majority of the osteocytes are phagocytosed and
      degraded by osteoclasts at sites of intense bone resorption, and that during
      endochondral ossification, substantial numbers of late hypertrophic chondrocyte
      cells undergo cell death.

PMID- 8864904
TI  - Mineral anisotropy in mineralized tissues is similar among species and mineral
      growth occurs independently of collagen orientation in rats: results from
      acoustic velocity measurements.
AB  - It has been reported that the mineral crystals in long bones have their c-axis
      aligned with the bone axis, presumably because collagen fibrils in bone also
      align with the bone axis. However, the predominant collagen orientation in bone
      often does not appear to be aligned with the mineral crystals, especially in rat
      primary bone. We hypothesized that mineral orientation in bone is not necessarily
      related to collagen orientation. An acoustic microscope was used to measure
      elastic constants of mineralized tissues from rat, cow, monkey, and human bone,
      and mineralized turkey leg tendon (MTLT). Measurements were made before and after
      demineralization with 10% ethylenediaminetetraacetic acid (EDTA) or
      decollagenization with 7% sodium hypochlorite. The elastic anisotropy ratio (AR)
      was defined as the ratio of the elastic coefficient in the longitudinal direction
      to the elastic coefficient in the transverse direction. Anisotropy ratios of
      mineralized tissues were not affected by formalin fixation or plastic embedding.
      An evaluation of tissues from the different species showed that the AR after
      decollagenization was not significantly different (p > 0.4, analysis of variance)
      among the groups, while AR after demineralization varied from 1.04 (rat bone) to
      1.51 (MTLT). There was no correlation between AR after demineralization and AR
      after decollagenization (r = 0.13, p = 0.5). This showed that the elastic
      anisotropy of collagen is more variable than mineral anisotropy in bone and MTLT.
      Another experiment showed that mineralization of turkey leg tendon changes the
      elasticity of the collagen matrix, making it less anisotropic. A final,
      prospective experiment was performed in which tibiae of rats were subjected to
      mechanical loading for 16 weeks. After 12 days, new periosteal woven bone was
      observed on the tibiae and, after 16 weeks, this new bone was consolidated and
      mineralized. Mineral in the newly formed woven bone was virtually isotropic (AR =
      1.07) after 12 days of loading, then became more anisotropic (AR = 1.52) after 16
      weeks of mechanical loading, as the mineral density of the new bone increased.
      This increase in anisotropy of bone mineral occurred even though the collagen
      matrix was woven and had no measureable fibril orientation. We conclude that (1)
      collagen anisotropy and mineral anisotropy are not necessarily correlated in
      mineralized tissues, (2) mineralization can affect the collagen matrix elasticity
      of mineralized tissues, and (3) an organized mineral structure can form in the
      absence of an organized collagen matrix.

PMID- 8864905
TI  - Strontium distribution and interactions with bone mineral in monkey iliac bone
      after strontium salt (S 12911) administration.
AB  - The analysis of the interaction of strontium (Sr) with bone mineral is of
      interest because a new agent containing Sr (S 12911) has shown positive effects
      on bone mass in various animal models of osteoporosis and is currently being
      developed for preventive and curative treatment of postmenopausal osteoporosis.
      Iliac bone samples were obtained from 20 male monkeys: 4 untreated control
      animals, 12 animals sacrificed at the end of a 13-week treatment with high dose
      levels of S 12911 (750, 275, or 100 mg/kg/day orally), and 4 animals sacrificed 6
      weeks after the end of a 13-week treatment with S 12911 (750 or 100 mg/kg/day
      orally). The distribution of Sr was determined and quantified by X-ray
      microanalysis. Changes at the crystal level were evaluated by X-ray diffraction
      and Raman microspectrometry. In the control animals, traces of Sr were found to
      be homogeneously distributed throughout the bone tissue. In the treated monkeys,
      Sr could only be detected in calcified matrix. In monkeys sacrificed at the end
      of the treatment, Sr was found to be dose-dependently incorporated into the
      mineral substance of the compact and cancellous bone. Sr was heterogeneously
      distributed with three to four times more Sr in new than in old compact bone, and
      approximately two and a half times more Sr in new than in old cancellous bone.
      The bone Sr content dramatically decreased in the animals sacrificed 6 weeks
      after the end of the treatment. Diffraction showed no significant changes in the
      characteristics of the crystal lattice. Sr appeared to be easily exchangeable
      from bone mineral and was slightly linked to mature crystals through ionic
      substitutions. Even at the highest dose level tested, less than 1 calcium ion out
      of 10 was substituted by 1 Sr ion in each crystal. In conclusion, taken up by
      bone, Sr was heterogeneously distributed with a higher concentration in new than
      in old bone but induced no major modifications of the bone mineral
      (crystallinity, crystal structure) at the crystal level. As a result, a treatment
      with S 12911 Sr salt should not induce any alteration of bone mineral.

PMID- 8864906
TI  - Insulin receptor expression in bone.
AB  - Insulin is known to be an important osteotropic hormone. To date, no study has
      specifically addressed the possibility that insulin receptor expression may be
      regulated by differentiation in bone. We report a heterogeneous distribution of
      insulin receptor (IR) within neonatal rat calvaria using a specific monoclonal
      antibody to the beta-subunit of the rat insulin receptor (CT-1). Specific binding
      of CT-1 to mature osteoblasts was demonstrated, with little binding over
      periosteal tissues or osteocytes. Using enzymatically derived subpopulations of
      calvarial cells, we showed a correlation between alkaline phosphatase activity
      and insulin-stimulated 2-deoxyglucose (2-DOG) uptake and increased 125I-insulin
      binding. Since primary calvarial cultures contain many cell types, we compared
      125I-insulin binding, insulin-stimulated 2-DOG uptake, and Northern blot analysis
      of IR mRNA in the clonal preosteoblast-like cell line UMR 201-10B and the mature
      osteoblast cell line UMR 106-01. It is shown that UMR 106-01 cells possess higher
      levels of IR mRNA, insulin binding, and insulin-stimulated glucose uptake, and
      that insulin up-regulated expression of mRNA of the glucose transporter GLUT1 by
      3-fold. In contrast, insulin binding was negligible in UMR 201-10B cells, which
      expressed much lower levels of IR mRNA. UMR 201-10B cells did not possess an
      insulin-sensitive glucose uptake system, although they express GLUT1 mRNA. These
      data are consistent with the hypothesis that, as in muscle and fat, insulin
      receptor expression correlates with the stage of osteoblast differentiation in
      vivo and in vitro.

PMID- 8864907
TI  - Dietary (n-3) and (n-6) polyunsaturates and acetylsalicylic acid alter ex vivo
      PGE2 biosynthesis, tissue IGF-I levels, and bone morphometry in chicks.
AB  - This study examined the effects of dietary (n-6) and (n-3) polyunsaturated fatty
      acids (PUFA) and acetylsalicylic acid (ASA) on bone ash content, morphometry,
      fatty acid composition, ex vivo PGE2 biosynthesis, tissue IGF-I concentration,
      and serum alkaline phosphatase (ALPase) activity in chicks. Newly hatched chicks
      were fed a semipurified diet containing soybean oil (S) or menhaden oil /
      safflower oil (M) at 90 g/kg. At 4 days of age, chicks were divided into four
      equal treatment groups receiving 0 mg [symbol: see text] or 500 mg [symbol: see
      text] of ASA/kg of diet: S[symbol: see text]ASA, M[symbol: see text]ASA,
      S[symbol: see text]ASA, and M[symbol: see text]ASA. Lipid and ASA treatments did
      not affect bone length, bone ash, or bone mineral content in chicks. Chicks fed M
      had increased fractional labeled trabecular surface and tissue level bone
      formation rates, independent of ASA treatment, compared with those given S. A
      significant fat x ASA interaction effect was found for trabecular bone volume,
      thickness, separation, and number. Chicks fed S had higher 20:4(n-6) but lower
      20:5(n-3) concentrations in liver and bone compared with those given M. Ex vivo
      PGE2 biosynthesis was higher in liver homogenates and bone organ cultures of
      chicks fed S compared with the values for those given M at 17 days. ASA treatment
      decreased ex vivo PGE2 production in liver homogenates and bone organ cultures of
      chicks, independent of the dietary lipids. Chicks fed ASA had a lower
      concentration of IGF-I in tibiotarsal bone compared with those not given ASA at
      19 days. Serum ALPase activity was higher in chicks given M compared with those
      fed S, but the values were reversed with ASA feeding. This study demonstrated
      that both dietary fat and ASA modulated bone PGE2 biosynthesis, and that (n-3)
      PUFA and fat x ASA interactions altered bone morphometry.

PMID- 8864908
TI  - The effect of weight-bearing exercise on bone mineral density: a study of female
      ex-elite athletes and the general population.
AB  - The aim of this retrospective cohort study was to estimate the changes in bone
      mineral density (BMD) as a consequence of exercise in female ex-athletes and age
      matched controls. Eighty-three ex-elite female athletes (67 middle and long
      distance runners, 16 tennis players, currently aged 40-65) were recruited from
      the original records of their sporting associations. Controls were 585 age
      matched females. The main outcome measures were BMD of lumbar spine (LS), femoral
      neck (FN), and forearm, estimated by dual-energy X-ray absorptiometry (DXA) scan.
      Levels of physical activity were assessed using a modified Allied Dunbar Fitness
      Survey scale and classified as (a) ex-athletes, (b) active controls (> or = 1 h
      of vigorous physical activity currently and in the past), (c) low activity
      controls with inconsistent or intermediate levels of activity, and (d) inactive
      controls (< 15 minutes of exercise per week). After adjustment for differences in
      age, weight, height, and smoking, athletes had greater BMDs than controls: 8.7%
      at the LS (95% confidence interval [CI] 5.4-12.0; p < 0.001) and 12.1% at FN (CI
      9.0-15.3; p < 0.001). The benefits of exercise appeared to persist after
      cessation of sporting activity. Active controls (n = 22) had greater BMDs than
      the inactive group (n = 347): 7.9% LS (CI 2.0-13.8; p = 0.009) and 8.3% FN (CI
      2.7-13.8; p = 0.004). The low activity controls (n = 216) had an intermediate
      BMD. Tennis players had greater BMDs compared with runners: 12.0% LS (CI 5.7
      18.2; p = 0.0004) and 6.5% FN (CI -0.2-13.2; p = 0.066). The BMD of tennis
      players' dominant forearms were greater than their nondominant forearms. In
      conclusion, regular vigorous weight-bearing exercise of 1 h or more per week is
      associated with an increase in BMD within a normal population. This study
      confirms long-term weight-bearing exercise as an important factor in the
      regulation of bone mass and fracture prevention.

PMID- 8864909
TI  - Effects of immobilization, three forms of remobilization, and subsequent
      deconditioning on bone mineral content and density in rat femora.
AB  - Disuse is associated with bone loss, which may not be recoverable. It is not
      known whether intensified remobilization is beneficial in restoring disuse
      related bone loss nor if any such benefit would depend upon continuing
      mobilization for its maintenance. After an immobilization period of 3 weeks, the
      effects of free remobilization (11 weeks), and low-and high-intensity treadmill
      running (11 weeks) with and without subsequent deconditioning (18 weeks) on the
      bone mineral content (BMC) and density (BMD) of the hindlimb femora of Sprague
      Dawley rats (n = 98) were studied using a dual-energy X-ray absorptiometric (DXA)
      scanner. Our hypothesis was that intensified remobilization is beneficial in
      restoring the BMC and BMD from disuse to normal while subsequent deconditioning
      is deleterious to these parameters. Immobilization for 3 weeks produced a
      significant BMC and BMD loss in the immobilized left femur (range -4.4 to -12.8%;
      p < 0.05-0.001). In the groups with free remobilization (free cage activity), the
      body weight-adjusted BMCs and BMDs always remained below those in the controls
      (range -2.3 to -12.1%; p values ranging from NS to < 0.01). Both low- and high
      intensity running restored BMC and BMD in the immobilized limb, the effect being
      better in the latter group. In both of these groups, the values of the
      immobilized left limbs and those of the free right limbs exclusively exceeded the
      corresponding values of the age-matched control rats (left limb values 3.0-21.1%
      higher with p values ranging from NS to < 0.01; right limb values 7.9-21.4%
      higher with p < 0.05-0.01). However, after the deconditioning period of 18 weeks,
      the above described beneficial effects of low- and high-intensity running were
      lost, the left and right limb BMC and BMD values being lower than those in the
      age-matched controls (range -3.8 to -8.7%; p values ranging from NS to < 0.05).
      In conclusion, this study clearly indicates the need for greater than normal
      activity to restore the BMC and BMD after disuse to normal levels. However, the
      benefits of intensified remobilization are lost if the activity is terminated,
      and therefore, after immobilization and disuse, bone loading activities should be
      continued, perhaps indefinitely.

PMID- 8864910
TI  - Predictors of ankle and foot fractures in older women. The Study of Osteoporotic
      Fractures Research Group.
AB  - To determine risk factors for ankle and foot fractures, data collected from 9704
      women 65 years of age or older from four areas of the United States were
      analyzed. Self-reported baseline questionnaires covered areas such as lifestyle
      factors (physical activity, diet, and smoking habits) and functional impairment
      (history of fracture, falling, and other diseases). Bone mineral density (BMD)
      and performance on neuromuscular tests were also measured. During 5.9 years of
      follow-up, 191 women fractured an ankle and 204 women fractured a foot.
      Proportional hazard models were used to estimate relative risks. In multivariable
      models, factors associated with ankle fracture included one or more falls in the
      year prior to baseline (relative risk [RR] 1.5; 95% confidence interval [CI] 1.1
      2.1), greater vigorous physical activity (RR per 2 times/week, 1.2; CI 1.1-1.3),
      weight gain since age 25 (RR per 20% gain, 1.4; CI 1.2-1.5), self-reported
      osteoarthritis (RR 0.5; CI 0.3-0.8), a sister's history of hip fracture after age
      50 (RR 1.7; CI 1.0-3.0), out of house < or = 1 per week (RR 3.0; CI 1.4-6.6), and
      low distal radius BMD (RR per -0.1 g/cm2, 1.2; CI 1.0-1.4). Factors associated
      with foot fracture included insulin-dependent diabetes (RR 2.9; CI 1.2-7.2), use
      of seizure medications (RR 2.3; CI 1.0-5.7) or of benzodiazepines (RR 1.5; CI 1.1
      2.2), history of hyperthyroidism (RR 0.5; CI 0.3-1.0), poor far depth perception
      (RR 0.7; CI 0.5-1.0), and low distal radius BMD (RR per -0.1 g/cm2, 1.3; CI 1.1
      1.5). Ankle and foot fractures have different profiles of risk factors that are
      largely independent of low bone mass.

PMID- 8864911
TI  - Prediction of fracture load at different skeletal sites by geometric properties
      of the cortical shell.
AB  - Quantitative bone assessment today is primarily based on the analysis of bone
      mineral density (BMD). The geometric properties of bone, which are an important
      parameter for skeletal strength, are generally not considered in the routine
      clinical assessment of osteoporosis. This study combined the geometric properties
      and the BMD values determined by peripheral quantitative computed tomography
      (pQCT) at the distal radius and at the femoral neck to predict fracture loads of
      the radius, femur, and lumbar vertebrae of 20 cadavers. Generalized osteopenia
      reduced the fracture loads at all three sites (p < 0.001). The strength of the
      radius and the femoral neck could best be predicted by considering either the
      second moment of inertia and trabecular BMD (R = 0.93) or the moment of inertia
      and the cortical BMD (R = 0.91). The geometric properties at the distal radius
      were highly correlated with the fracture load at the same skeletal site (R =
      0.89) and were also used to estimate the fracture risk at the lumbar vertebrae (R
      = 0.75) and at the femoral neck (R = 0.87). We conclude that both geometry and
      density contribute substantially to the strength of the skeleton. The screening
      for osteoporosis and the prediction of fracture risk can be improved, therefore,
      by an additional consideration of the geometric properties of the cortex.

PMID- 8864912
TI  - Normal ranges for vertebral height ratios and prevalence of vertebral fracture in
      Hong Kong Chinese: a comparison with American Caucasians.
AB  - We have established the normal ranges for vertebral height ratios and studied the
      prevalence of vertebral fracture in 481 Chinese women aged 70-79. Our results
      were compared with those of an American study with a similar methodology. Lateral
      spine radiographs centered at T8 and L3 were taken, and the anterior, middle, and
      posterior vertebral heights of each vertebra from T5 to L4 were measured. The
      means and standard deviations (SDs) of the anterior to posterior, middle to
      posterior, and posterior to posterior vertebral height ratios were derived after
      trimming the extreme values from the distribution. The Chinese had smaller
      vertebral size than the American Caucasians at all levels. Moreover, the anterior
      to posterior vertebral height ratios were consistently smaller in the Chinese
      than in the Americans from T10 onward. The means of other vertebral height ratios
      in the Chinese were similar to the American Caucasians, but the SDs were greater
      in the Chinese. The prevalence of vertebral fracture was 29% in the Chinese and
      25% in the American Caucasians if a cut-off of 3 SD below the mean for vertebral
      height ratios was used. We conclude that population-specific means and SD should
      be used for defining vertebral fracture and that the prevalence of vertebral
      fracture is similar in Hong Kong Chinese and American Caucasians.

PMID- 8864913
TI  - Fluoride and the FDA: a curious case.

PMID- 8864914
TI  - Calcifying and ossifying soft tissue lesions presenting in the skin.

PMID- 8864915
TI  - T-cell receptor beta variable region (V beta) usage in cutaneous T-cell lymphomas
      (CTCL) in comparison to normal and eczematous skin.
AB  - Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of
      lymphoproliferative disorders. We investigated the variable region (V beta) of
      the T-cell receptor (TCR) repertoire in CTCL and compared it to the V beta
      repertoire in normal and eczematous skin. We used a panel of 21 anti-V beta
      antibodies and investigated 84 biopsies of 71 CTCL patients (4 parapsoriasis en
      grandes plaques (PA), 1 lymphomatoid papulosis, 29 mycosis fungoides (MF), 13
      Sezary syndrome (SS), 1 CD8+ CTCL, 11 pleomorphic CTCL (PLEO), 12 CTCL nor
      classified). Six biopsies of normal skin and 6 of eczematous skin lesions served
      as controls. We determined the frequency of the V beta in normal and inflamed
      skin and compared it to the percentage of the respective V beta in the malignant
      clone of the CTCL patients. The percentage of the V beta positive CD4+ cells in
      relation to the total number of T cells in normal skin and inflamed skin differed
      from the distribution of the V beta families in the peripheral blood mononuclear
      cells (PBMC). Out of 71 CTCL cases, the clone was identified in 23 (32%). We
      identified the following clones: 1 V beta 3.1 (16MF), 7 V beta 5.1 (1 CD8+ CTCL,
      1 CTCL not classified, 1 MF, 1 PA, 3 SS), 1 V beta 6.7 (1 SS), 7 V beta 8.1/8.2
      (2 CTCL not classified, 1 PLEO, 2 MF, 2 SS), 1 V beta 12.1 (1 PLEO), 3 V beta
      17.1 (2 CTCL not classified, 1 MF), 2 V beta 22.1 (1 CTCL not classified, 1 MF),
      1 TCR delta (SS). The frequency of the malignant clone V beta usage corresponded
      well to the repertoire of V beta in eczematous skin but not to the repertoire in
      PBMC. In 6 patients, the malignant clone was mainly localized in the epidermis.
      In 17 cases, the clone-specific cells were distributed in epidermis and dermis
      equally. A retrospective analysis showed that preferential epidermal homing of
      the clone was associated with a non-aggressive clinical course. The V beta usage
      of CTCL and eczema suggests a special cutaneous microenvironment which might be
      co-created by certain (bacterial?) superantigens. A preferential epidermal homing
      of the clone might have prognostic implications.

PMID- 8864917
TI  - The role of alpha E beta 7 integrin (CD103) and E-cadherin in epidermotropism in
      cutaneous T-cell lymphoma.
AB  - Adhesion molecules such as integrins and cadherins are thought to play a critical
      role in T-cell migration and localization within the epidermis (epidermotropism).
      The purpose of this study was to correlate T-cell expression of the integrin
      CD103 and E-cadherin in cutaneous T-cell lymphoma (CTCL). Serial sections of skin
      biopsies from 22 patients with CTCL and 13 with benign reactive dermatitis were
      stained with antibodies to CD4, CD103, and E-cadherin by the avidin-biotin
      peroxidase technique. CD103 was expressed on single epidermotropic CD4+ T-cells
      in 9/9 early stage (patch/plaque) CTCL and 6/10 reactive dermatitis biopsies.
      Less than 30% of dermal T-cells expressed CD103. All 4/4 late stage (tumor) CTCL
      were CD103-. Epidermal aggregates of CD4+ T-cells (Pautrier's microabscesses)
      were CD103-. E-cadherin was expressed on epidermal keratinocytes and follicular
      and sweat gland epithelia but not on T-cells. We conclude that CD103 expression
      on cutaneous T-cells parallels the degree of epidermotropism exhibited in both
      neoplastic and inflammatory disorders of the skin. E-cadherin is not expressed on
      T-cells infiltrating the skin. Further investigation is necessary to further
      elucidate the interaction between CD103 and E-cadherin in facilitating
      trafficking of T-cells into the epidermis.

PMID- 8864916
TI  - Correlation between clonotypic T-cell receptor beta chain variable region (TCR-V
      beta) gene expression and aberrant T-cell antigen expression in cutaneous T-cell
      lymphoma.
AB  - Immunohistochemical studies can augment the clinicopathologic diagnosis of
      cutaneous T-cell lymphoma (CTCL). Our goal was to determine whether a panel of 11
      T-cell receptor (TCR) beta chain variable region (V beta) monoclonal antibodies
      (moAbs) could consistently identify clonal T-cell populations within CTCL skin
      infiltrates, and whether these cell exhibited aberrant T-cell antigen expression.
      Biopsies from 24 CTCL and 3 parapsoriasis patients were analyzed. Of the 27
      patients, 4 (15%) demonstrated T-cell clonality by restricted TCR-V beta moAb
      staining. The V beta + restricted cells expressed aberrant antigen profiles.
      Overall, aberrant antigen profiles were detected in 18/24 (75%) CTCL. Patients. V
      beta 18 moAb crossreacted with a 85 kD protein produced by basal and suprabasal
      keratinocytes. We conclude: 1) Restricted TCR-V beta expression correlated with
      aberrant T-cell antigen profiles: 2) In the absence of a complete panel of TCR-V
      beta moAbs, localization of aberrant T-cell antigen expression can be useful in
      identifying malignant T-cells within CTCL skin infiltrates; 3) The detection
      sensitivity and specificity of the currently available TCR-V beta moAbs may limit
      their utility to consistently detect clonal T-cell populations in CTCL skin
      biopsies; 4) A 85 kD protein present on basal and suprabasal keratinocytes is
      recognized by V beta 18 moAb and may be related to immune function(s) of the
      epidermis.

PMID- 8864918
TI  - The role of MT2 and anti-bcl-2 protein antibodies in the differentiation of
      benign from malignant cutaneous infiltrates of B-lymphocytes with germinal center
      formation.
AB  - MT2/CD45RA and anti-bcl-2 protein (Bcl-2) monoclonal antibodies are useful
      markers in distinguishing follicular lymphomas from reactive follicular
      hyperplasia of the lymph nodes. We examined biopsy specimens from 11 patients
      with primary cutaneous B-cell follicle center lymphomas, 10 patients with
      cutaneous pseudolymphomas with germinal centers, and 6 patients with inflammatory
      infiltrates with germinal centers in non-lymphoid cutaneous tumors (3 basal cell
      carcinomas, 2 malignant melanomas, and 1 solar keratosis), in order to evaluate
      the utility of MT2 and anti-Bcl-2 antibodies in differentiating benign from
      malignant germinal center cell proliferations in the skin. Immunohistochemical
      evaluation of MT2 and Bcl-2 was focused exclusively on the reactivity of germinal
      center cells. Specific membranous MT2 positivity was found in 2/11 cutaneous
      follicle center lymphomas; a diffuse, non-specific staining pattern was
      identified in 3/11 follicle center lymphomas and in 1/6 inflammatory infiltrates
      in non-lymphoid tumors. A negative MT2 reaction was observed in 6/11 follicle
      center cell lymphomas, in all cases of pseudolymphomas and in 5/6 inflammatory
      infiltrates in non-lymphoid tumors. Bcl-2 positivity was detected only in 1/11
      follicle center lymphomas. Germinal center cells in all other cases were Bcl-2
      negative. Our results suggest that MT2 and anti-Bcl-2 antibodies are only of
      limited value in differentiating primary cutaneous follicle center lymphomas from
      cutaneous pseudolymphomas with germinal centers.

PMID- 8864919
TI  - Extranodal spread of anaplastic large cell (CD30+) lymphoma presenting as a
      cutaneous perivascular infiltrate.
AB  - Cutaneous lesions of anaplastic large cell (CD30+) lymphoma (ALCL) typically
      present as solitary or multiple ulcerated nodules. This tumor is histologically
      characterized by a diffuse dermal and sometimes subcutaneous infiltrate composed
      of bizarre, pleomorphic, neoplastic cells that may be occasionally
      multinucleated. We report a case of extranodal spread of ALCL to the skin in a 2
      1/2-year-old boy presenting as a widespread papular eruption that on biopsy
      showed lymphoma restricted to the perivascular and periadnexal dermis.

PMID- 8864920
TI  - Persistent cutaneous pseudolymphoma after intradermal gold injection.
AB  - After intradermal testing with goldsodiumthiomalate (GSTM), 5 out of 8 patients
      developed skin papules at the test sites, which persisted up to 20 months. The
      lesions were surgically excised. Histology revealed pseudolymphoma of B and T
      cell type containing follicular structures and occasional small granulomas. The
      amount of histiocytic cells among B and T lymphocytes was pronounced, including
      acid cysteine proteinase inhibitor (ACPI) positive follicular dendritic cells,
      CD68 positive macrophages, factor XIIIa positive dermal dendrocytes and S-100
      positive cells. By electron microscopy, the macrophages contained endosomes
      loaded with crystalloid material which contained gold in X-ray microanalysis.
      Atomic absorption spectrophotometry also confirmed the presence of gold in one
      specimen. Thus GSTM seemed to accumulate in tissue macrophages leading to
      constant immunologic activation with lymphoid proliferation and histiocytic
      response.

PMID- 8864921
TI  - Nuclear morphometry, immunohistochemical staining with Ki-67 antibody and mitotic
      index in the assessment of proliferative activity and prognosis of primary
      malignant melanomas of the skin.
AB  - Nuclear morphometry, immunohistochemical staining with Ki-67 antibody and mitotic
      index were studied in primary cutaneous malignant melanomas. The number of Ki-67
      positive cells/ 200 tumor cells did not correlate with any nuclear morphometrical
      parameters, and it only approached but did not reach significant correlation with
      melanoma thickness according to Breslow. The nuclear area, short axis and long
      axis correlated with melanoma thickness, but the nuclear axis ratio (which
      reflects the sphericity of nuclei) and melanoma thickness did not show
      significant correlation. Mitotic index was higher in thick melanomas and in
      melanomas with high Ki-67 positivity, large nuclear area, long nuclear short
      axis, and small nuclear axis ratio. In Cox's stepwise proportional hazard model,
      melanoma thickness and the nuclear axis ratio were significant independent
      prognostic factors for patient survival, while the nuclear area, short axis and
      long axis, gender, age, Clark level, mitotic index and Ki-67 positivity lacked
      significant independent prognostic value. The results suggest that the
      proliferative activity of tumor cells does not alone explain the great importance
      of tumor thickness as prognosticator in melanoma. The thickness of melanoma
      measured according to Breslow and the nuclear axis ratio are more efficient
      prognosticators in melanoma than parameters associated with proliferation.

PMID- 8864922
TI  - The value of Nm23 expression as an independent prognostic indicator in primary
      thick melanoma.
AB  - Whilst tumour thickness is of great value in predicting prognosis for groups of
      patients in different categories, it is of less value for individual patients. It
      has been proposed that expression of the nm23 gene, a putative tumour suppressor
      gene, is associated with improved outcome in a number of human neoplasms
      including malignant melanoma. We assessed nm23 expression in 22 patients who had
      primary melanomas > 3mm thick. Ten have survived to date and 12 died of melanoma.
      Using immunohistochemical methods, we found no significant differences in gene
      expression between the two groups.

PMID- 8864923
TI  - Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and
      lichen sclerosus et atrophicus: a PCR study of thirty-five cases.
AB  - Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share
      common features with acrodermatitis chronica atrophicans (ACA), a known chronic
      form of borreliosis. These include similar histologic findings such as diffuse
      dermal fibrosis. These observations have led several investigators to consider
      the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among
      all of these diseases. The aim of this study is to investigate the role of Bb in
      the pathogenesis of morphea and LSA, by assaying for its presence in lesional
      skin biopsies from patients with these diseases. We utilized the nested
      polymerase chain reaction (PCR) technique to selectively amplify a longer segment
      of a Bb-specific somatic gene, on DNA from paraffin-embedded, formalin-fixed
      tissues. The results revealed no Bb-specific DNA sequence in 28 specimens of
      morphea/scleroderma and 7 of LSA with varying stages of disease. Furthermore,
      confirmatory Southern blot of the PCR product, resulted in similar findings.
      These data seriously question the role played by this spirochete in the
      pathogenesis of morphea and LSA, at least in the southeastern part of the USA.

PMID- 8864924
TI  - Apoptotic cell death in formation of vesicular skin lesions in patients with
      acquired zinc deficiency.
AB  - We investigated the role of apoptotic cell death in the production of skin
      lesions in patients with acquired zinc deficiency. Nuclear condensation of
      keratinocytes was observed at an early stage of skin lesions in patients with
      zinc deficiency, especially around vesicular lesions. Nuclei of keratinocytes in
      perivesicular lesions of the epidermis were positively stained by the nick-end
      labeling specific for fragmented DNA. Lewis Y antigen was also expressed on
      perivesicular lesions. On the other hand, there were no such positively stained
      cells in hyperkeratotic skin lesions of the patients. Therefore, it was suggested
      that apoptotic cell death might play a role in the formation of vesicular skin
      lesions in patients with zinc deficiency, but not in the formation of
      hyperkeratotic skin lesions.

PMID- 8864925
TI  - Cutaneous angiomyolipoma.
AB  - Extrarenal angiomyolipomas are rare lesions. An angiomyolipoma located on the
      right ear lobe in a 49-year-old man is reported. Pathologic examination showed a
      well-circumscribed subcutaneous nodule, 2 cm in diameter. The components of the
      tumor were confirmed by immunohistochemistry. Reactivity for HMB-45 was negative.
      A review of the twelve published cases, including the present, reveals that the
      patients age ranged from 33 to 77 years (mean 53.6), the male/female ratio was
      11.1. The tumors were solitary, asymptomatic, noninvasive, located most commonly
      in acral skin or on the ear. The clinical impression is that of a cyst, a lipoma
      or a vascular tumor. Signs of tuberous sclerosis were absent in all cases. In
      contrast to the renal form, the cutaneous angiomyolipoma is a tumor differing in
      sex predominance, clinical associations, circumscription, solitariness, and HMB
      45 immunoreactivity. Distinction from other mesenchymal lesions depends on
      recognition of traditional histologic criteria.

PMID- 8864926
TI  - Extra-acral calcifying aponeurotic fibroma: a distinctive case with 23-year
      follow-up.
AB  - Calcifying aponeurotic fibroma (CAF) is an unusual but well-characterized soft
      tissue neoplasm that typically involves the digits of children and frequently
      recurs locally. This report describes a case from the subcutis of the lumbosacral
      region. A 26-year-old man initially presented at age 3 and developed three
      recurrences over a 23-year period each at approximately 8-year intervals (ages
      10, 18, and 26). The microscopic findings in all recurrences showed a lobulated,
      poorly circumscribed proliferation of dense fibrous tissue containing epithelioid
      like fibroblasts, multinucleated cells, and islands of metaplastic chondroid
      differentiation with focal calcification. Despite origin from an unusual anatomic
      site, this case reported herein demonstrates the classical morphologic features
      and clinical history of CAF which showed little in the way of morphologic
      evolution despite 23 years of persistence. The clinical and histologic features
      helpful in distinguishing CAF from infantile fibromatosis and soft tissue
      chondroma are discussed.

PMID- 8864927
TI  - Fibro-osseous pseudotumor of the digit: a comparison to myositis ossificans by
      light microscopy and immunohistochemical methods.
AB  - Fibro-osseous pseudotumor of the digit is an unusual cutaneous process
      characterized histologically by a fibroblastic proliferation admixed with
      reactive/metaplastic osteoid formation. The osteoid formation can be florid and
      immature, mimicking the appearance of malignant osteoid-forming neoplasms. Fibro
      osseous pseudotumor of the digit has histologic and clinical features in common
      with myositis ossificans. This has led many to consider the two to be synonymous.
      We studied three cases of fibro-osseous pseudotumor, compared to five cases of
      myositis ossificans, using routine light microscopy and a battery of
      immunohistochemical stains. Both entities displayed a "zoning" pattern of
      immature spindled areas admixed with more mature areas having osteoid metaplasia.
      This was more pronounced in myositis ossificans. In each lesion, the spindle
      cells stained positively for vimentin and actin. CD34 and Factor VIII highlighted
      the vasculature. No stromal staining for MAK-6 (cytokeratin) or S-100 was
      identified. Ki-67, a proliferation marker, showed positive staining of the
      stromal cells in both lesions, which was strongest in the immature spindled
      areas. The immunohistochemical and histologic similarities of the lesions support
      fibro-osseous pseudotumor of the digit being a cutaneous variant of myositis
      ossificans.

PMID- 8864928
TI  - Ossifying fibromyxoid tumor of soft parts: a case report and review.
AB  - Ossifying fibromyxoid tumor of soft parts is a recently described, rare but
      morphologically distinctive tumor of soft tissue, including subcutaneous soft
      tissue. We report a case of ossifying fibromyxoid tumor of soft parts which
      occurred in the subcutaneous tissue of a 68-year-old male, and review the
      clinical, histologic, and immunohistologic features of this tumor. Ossifying
      fibromyxoid tumor of soft parts tends to occur in the subcutaneous tissue and
      have been reported from the head and neck, upper and lower extremities, and
      trunk. Immunohistologic studies have supported a neural origin. While considered
      benign, local recurrence after excision is common and these tumors should be
      excised with clear margins to prevent recurrence.

PMID- 8864929
TI  - Ossifying fibromyxoid tumor of soft parts.
AB  - Ossifying fibromyxoid tumors (OFT) of soft parts are very rare neoplasms recently
      described by Enzinger et al. (1). They usually present as well-circumscribed,
      slow-growing, asymptomatic subcutaneous masses. A characteristic finding is a
      fibrous capsule and an incomplete peripheral shell of mature bone. Although most
      cases behave as benign tumors, a high rate of local recurrences have been
      described. We describe a 43-year-old male with a perianal subcutaneous tumor of
      10 years evolution. The histopathology was compatible with OFT. Due to the
      subcutaneous location of OFT, both the dermatologist and dermatopathologist need
      to know about this rare tumor.

PMID- 8864930
TI  - Ossifying fibromyxoid tumor of soft parts of the back.
AB  - We report a first case of ossifying fibromyxoid tumor of soft parts of the back,
      a 10 x 9.5 x 6 cm well-circumscribed elevated subcutaneous tumor demarcated by an
      incomplete fibrous capsule with bone formation at its base. The tumor was
      composed of both myxomatous areas with spindle tumor cells and pseudoalveolar
      structures with oval tumor cells. The tumor cells had evenly sized, oval nuclei
      without atypia and slightly eosinophilic cytoplasm with intracellular vacuoles.
      Immunohistochemical studies revealed positivity for vimentin and focal positivity
      for S-100 protein. Ultrastructural examination revealed a few filopodia-like
      processes, discontinuous basal lamina and a few primitive cell junctions. Based
      on these immunohistochemical and ultrastructural results, this tumor may be
      related to Schwann's cells. There has been no recurrence 5 years after wide local
      excision.

PMID- 8864931
TI  - Acute phase response in heifers with experimentally induced mastitis.
AB  - Ten pregnant heifers were inoculated in both hind udder quarters with a mixture
      of Actinomyces pyogenes, Fusobacterium necrophorum and Peptostreptococcus
      indolicus. Development of the experimental mastitis was monitored by sequential
      clinical and bacteriological examinations, and by blood acute phase protein
      profiles. Sequential changes in plasma fibrinogen, serum haptoglobin, acid
      soluble glyco-proteins and alpha 1-proteinase inhibitor activity were analysed
      and compared with both the clinical and bacteriological findings and the final
      outcome of the disease after calving. All ten heifers developed moderate to
      severe clinical mastitis. Four recovered completely, had a normal lactation after
      calving and exhibited only transient fever and moderate local signs. In six of
      the heifers the course of the disease was severe, and the inoculated quarters
      failed to produce milk after calving. The acute phase response of the four
      heifers that recovered was also significantly milder than that of the other six
      heifers. Haptoglobin and acid-soluble glycoproteins were most effective in
      indicating the severity of the infection and predicting the final outcome of the
      disease. Fibrinogen was a reliable indicator for detecting the presence of
      bacterial infection in all heifers. alpha 1-Proteinase inhibitor activity was of
      low diagnostic value in this study.

PMID- 8864932
TI  - Field study on the relationship between teat thickness changes and intramammary
      infections.
AB  - The aim of this study was to describe the results of teat thickness measurement
      applied routinely in three commercial dairy herds and to evaluate the influence
      of machine-induced teat thickness changes on intramammary infection and the
      frequency of new infection. A total of 1018 fore milk samples and the same number
      of teat apex measurements have been evaluated. Overall, relative teat thickness
      changes were normally distributed (mean -0.16%, SD 10.15%), while a specific
      pattern could be observed within herds. Increases in teat thickness of > 5% were
      significantly associated with infection and new infection (odds ratio > 1), but
      the association was not significant when teat thickness decreased by more than
      5%. When results were classified according to aetiology, analysis showed that
      coagulase-negative staphylococcal infections were significantly associated with
      both increases and decreases in teat thickness numerically greater than 5%.

PMID- 8864933
TI  - Relationship between thickness, chapping and Staphylococcus aureus colonization
      of bovine teat tissue.
AB  - Post-milking measurements of teat skin chapping score, teat thickness and
      colonization by Staphylococcus aureus were determined for 11.5 d. Three teats on
      each of twelve Holstein cows, free from Staph. aureus intramammary infections,
      were immersed in 1 M-NaOH solution to induce teat chapping; the fourth teat
      served as a control. To achieve different degrees of chapping, one teat per cow
      received one immersion after each milking for three consecutive milking periods,
      a second teat received two immersions, and the third teat received one immersion
      which coincided with the last immersion of the other two teats. All teats were
      challenged twice with a skim milk broth culture of Staph. aureus (5 x 10(6) cfu)
      after the first and second milking following NaOH treatment. Measures were
      initiated with the milking following the last Staph. aureus challenges. Tissue
      thickness of the lateral side of the teat (barrel) and colonization by Staph.
      aureus declined with time. Thickness of the teat end varied more erratically.
      Teat skin chapping score was positively correlated (P < 0.001) with tissue
      thickness of the barrel and Staph. aureus colonization. Thickness of the barrel
      was not significantly correlated with Staph. aureus colonization. Barrel
      thickness as a covariate had a significant effect (P < 0.05) on teat skin
      colonization of Staph. aureus, whereas teat skin score and teat end thickness had
      no significant effect. Thus, thickness of the lateral side of the teat explained
      the greatest variation in Staph. aureus teat skin colonization in the model
      tested.

PMID- 8864934
TI  - Effect of somatic cell count and stage of lactation on the quality and storage
      life of ultra high temperature milk.
AB  - The effects of bulk milk cell count (BMCC) and stage of lactation on the quality
      and storage characteristics of UHT milk were investigated. The UHT milk was
      manufactured in a pilot plant using milk of low BMCC from early and late
      lactation, and milk of high BMCC from early and late lactation. Upon storage at
      20 degrees C, early lactation UHT milk gelled far ahead of late lactation milk.
      Within each stage of lactation, high BMCC milk tended to gel first. Few
      differences in the organoleptic properties of the UHT milks were observed. It was
      apparent that the onset of age gelation may not always be related directly to the
      level of proteolysis, and that other factors influencing milk composition and the
      reactions between milk components may play more important roles. At a particular
      stage of lactation, proteolysis induced by mastitis may hasten the onset of
      gelation.

PMID- 8864935
TI  - Phosphopeptides interacting with colloidal calcium phosphate isolated by tryptic
      hydrolysis of bovine casein micelles.
AB  - After extended tryptic hydrolysis of large bovine casein micelles, a mineral-rich
      peptide fraction was recovered by ultracentrifugation. Its mineral part contained
      72% of the colloidal Ca and 49% of the colloidal P1 originally present in the
      native micelle. Colloidal nitrogenous components were also present, amounting to
      27% of the original N content. They contained most of the phosphopeptides and 82%
      of the micellar phosphoseryl residues. These tryptic peptides were characterized
      by reversed-phase HPLC on-line electrospray ion source-mass spectrometry
      analysis. Among the peptides produced 14 phosphopeptides were identified: alpha
      s2-CN(1-24), alpha s2-CN(1-21), alpha s1-CN(43-79), alpha s1-CN(35-79)7P, alpha
      s1-CN(35-79)8P, alpha s1-CN(37-79), alpha s1-CN(104-119), alpha s1-CN(104-124),
      beta-CN(1-25), beta-CN(1-28), beta-CN(1-29), beta-CN(30-97), beta-CN(33-97) and
      beta-CN(29-97). The proportion of the phosphopeptides interacting with colloidal
      calcium phosphate was correlated with their relative content of phosphoserine
      residues, since phosphopeptides containing more than four phosphoserine residues
      were consistently present within this fraction. It also appeared that other types
      of peptides, some of them hydrophobic in nature, were also partly or completely
      present within the colloidal fraction, including alpha s1-CN(91-100), alpha s1
      CN(152-193), alpha s1-CN(23-34), alpha s1-CN(125-193), alpha s1-CN(125-199), beta
      CN(177-209). beta-CN(184-209), beta-CN(114-169) and beta-CN(108-169). Their
      possible involvement in the micellar backbone is discussed.

PMID- 8864936
TI  - Synthesis of plasminogen activator inhibitor 1 by bovine mammary epithelial and
      myoepithelial cell lines.
AB  - Conversion of plasminogen to plasmin provides an important source of proteolytic
      activity in the bovine mammary gland. Plasminogen activator inhibitor 1 (PAI-1)
      plays a key role in limiting plasminogen activation. The PAI-1 biosynthetic
      capabilities of various bovine mammary cells were determined. The immortalized
      epithelial cell lines MAC-T and BME-UV and the myoepithelial cell line BMM-UV
      were used as model systems. Northern blot analysis indicated that both epithelial
      and myoepithelial cells contained PAI-1 mRNA. Bovine PAI-1 was encoded by a
      single mRNA species approximately 3.0 kb long. BME-UV cells contained 2.0-fold (P
      < 0.01) the PAI-1 mRNA of MAC-T or BMM-UV cells. Reverse zymography indicated
      that both epithelial and myoepithelial cells synthesized PAI-1 protein with a
      molecular mass of approximately 50 kDa.

PMID- 8864937
TI  - Herpesvirus resistance to antiviral drugs: a review of the mechanisms, clinical
      importance and therapeutic options.
AB  - During the past decade, potent agents against herpes simplex virus (HSV) types 1
      and 2, varicella zoster virus (VZV), and cytomegalovirus (CMV) have become
      available. The increasing clinical use of acyclovir, ganciclovir, and foscarnet
      has been associated with the emergence of drug-resistant herpesvirus strains.
      Resistance to acyclovir or ganciclovir most frequently results from deficient
      intracellular phosphorylation of these agents which is required for drug
      activation. Resistance to foscarnet is due to viral DNA polymerase mutants that
      permit viral replication despite the presence of the drug. In immunocompetent
      patients, herpesvirus resistance is rare and generally does not correlate with
      clinical outcome. In contrast, in immunocompromised hosts, resistance of HSV,
      VZV, and CMV is increasingly detected, and may be associated with disease
      refractory to antiviral therapy. Foscarnet treatment has been used with some
      clinical benefit in patients with acyclovir-resistant HSV or VZV, or ganciclovir
      resistant CMV. For therapy of resistant mucocutaneous HSV disease, topical
      trifluorothymidine, and topical or intravenous cidofovir (HPMPC) have yielded
      encouraging results that warrant further investigation. Improved methods for
      detection of herpesvirus resistance, and validation of alternative therapy for
      patients with documented resistance are required to reduce the clinical impact of
      drug-resistant herpesviruses.

PMID- 8864939
TI  - Killing activity of microwaves in milk.
AB  - The killing activity of microwaves of 2450 MHz frequency and 600 W power on
      Pseudomonas aeruginosa, Escherichia coli, Enterobacter sakazakii, Klebsiella
      pneumoniae, Staphylococcus aureus, Candida albicans, Mycobacterium terrae and
      poliomyelitis vaccine-virus suspended in five infant formula preparations was
      investigated. The samples were brought to the boil (85-100 s depending on milk
      type). They had reached average temperatures of 82-93 degrees C at this point.
      Most of the vegetative organisms were killed. In those samples where growth was
      still detectable after microwave treatment, a significant reduction in viable
      micro-organisms (at least 5000-fold) was noted. We conclude that microwave
      beating to the boil is a convenient and fast method to reduce microbial
      contamination of infant feeds. However, care should be taken to ensure that milk
      is adequately cooled to the required temperature before it is fed to an infant.

PMID- 8864938
TI  - An outbreak of multiply-resistant Klebsiella pneumoniae in the Grampian region of
      Scotland.
AB  - A predominantly hospital-based outbreak of multiply-resistant Klebsiella
      pneumoniae capsular type K2 (MRK) expressing expanded spectrum betalactamase
      (ESBL) activity and fully sensitive only to the carbapenems and amikacin is
      described. The organism was isolated from 283 patients between March 1992 and
      September 1995. The outbreak started in the intensive care unit (ICU) of a major
      acute hospital and spread through surgical wards, a medical ward, a geriatric
      unit in a separate hospital and various other local hospitals. Environmental
      screening revealed extensive ward contamination. The decline of the outbreak
      after the spring of 1995 coincided with the re-emphasis of standard infection
      control procedures and the launch of a works programme aimed at addressing
      underlying sites of environmental contamination. Of the 283 cases, 166 (59.0%)
      were detected through a specially instigated case finding programme. The MRK
      caused 11 cases of septicaemia, two postoperative intra-abdominal abscesses, one
      case of postoperative meningitis, 102 cases of urinary tract infection and 28
      wound infections and was isolated from the respiratory tracts of five patients
      with ventilator associated pneumonia. The difficulty in controlling the outbreak
      is ascribed to heavy environmental contamination, frequent inter- and intra
      hospital patient transfers and prolonged carriage of the outbreak strain.

PMID- 8864940
TI  - Restriction endonuclease analysis of group B streptococcal isolates from two
      distinct geographical regions.
AB  - This study examined isolates of group B streptococci (GBS) by latex
      seroagglutination and restriction endonuclease analysis (REA). REA analysis was
      performed with high- and low-frequency cutting enzymes, and fragments were
      resolved by linear and pulsed-field gel electrophoresis (PFGE), respectively. GBS
      isolates were derived from a regional acute-care hospital and a tertiary referral
      obstetric hospital. The most common serotype isolated at the general hospital was
      serotype V (42%). A high incidence of this serotype V was associated with wound
      infections, but there was no predominant REA profile. Serotype III was the most
      common from the obstetric hospital (41%). The majority of these isolates were
      associated with neonatal GBS infection and there was a predominant restriction
      pattern. Analysis of restriction patterns of GBS isolated from individual mother/
      baby pairs revealed common patterns. These data extend the evidence for vertical
      transmission of GBS and clones of serotype III GBS with increased pathogenic
      potential.

PMID- 8864941
TI  - Staphylococcus aureus carriage and infections among patients in four haemo- and
      peritoneal-dialysis centres in Denmark. The Danish Study Group of Peritonitis in
      Dialysis (DASPID).
AB  - A three-month prospective surveillance study was undertaken in four dialysis
      centres to establish the prevalence of Staphylococcus aureus carriage in a Danish
      population of patients on haemodialysis (HD) or on continuous ambulatory
      peritoneal dialysis (CAPD). General data such as sex, age, diagnosis, number of
      months in dialysis, hospital and ward were registered on a precoded form.
      Standardized nose and four skin swabs (axillae, groins, perineum) were performed
      on the first day of the survey. After one and two months, nose swabs were
      collected. Infections were registered and cultures were sent for phage-typing
      together with the S. aureus strains isolated from the swabs; 59.5% of HD patients
      and 51.2% of CAPD patients carried S. aureus. Permanent carriage was most
      frequent (P < 0.00009), primarily in the nose (44.0 and 34.9%, respectively in HD
      and CAPD). Skin carriage alone was rare (2.4 and 4.7%). Approximately one third
      (36.6 and 40.7%) of infections were caused by S. aureus. Although diabetics were
      not significantly more frequent carriers (60.5%) than non-diabetics (55.0%), the
      incidence of infection was much higher (26.3% vs. 10.3%, P = 0.004). In CAPD,
      peritonitis and tunnel/exit-site infections predominated (81.4%), often caused by
      S. aureus (34.8%). More than two thirds of the infections in HD patients were
      related to intravascular catheterization. The most serious infection was
      septicaemia, in all cases due to S. aureus. S aureus infections occurred
      significantly more frequently among carriers (P = 0.005), and more than half the
      patients were infected by the same or possibly the same strain as they carried in
      the nose or on skin. Different regimens for the elimination of S. aureus carriage
      in dialysis patients are discussed. A policy for risk assessment of patients
      should be developed, and the elimination of S. aureus carriage before dialysis
      should be encouraged. Controlled trials comparing the cost-effectiveness of
      recommended regimens to eliminate carriage in HD/CAPD patients are needed. Nose
      swabs are reliable indicators of carriage in dialysis patients.

PMID- 8864942
TI  - Holy water--a risk factor for hospital-acquired infection.

PMID- 8864943
TI  - Use of holy water in hospitals.

PMID- 8864944
TI  - Appropriate precautions for insertion of epidural catheters.

PMID- 8864945
TI  - Outbreak of infection with penicillin-resistant pneumococci.

PMID- 8864946
TI  - Sialic acids and the metabolism of low density lipoprotein.
AB  - Sialic acid-poor low density lipoprotein (LDL) is suggested to be atherogenic
      because it causes in vitro accumulation of cholesterol into epithelial cells and
      macrophages. We studied whether the whole-body catabolism of LDL varies according
      to its sialic acid content by analyzing the sialic acids in total (d 1.019-1.063
      g/ml), light (d 1.019-1.036 g/ml), dense (d 1.037-1.055 g/ml), and very dense (d
      1.056-1.063 g/ml) LDL, and the kinetics of total and dense LDL apolipoprotein
      (apo) B in 20 non-insulin-dependent diabetic and 10 non-diabetic men of similar
      age, both groups without and with coronary artery disease (CAD). The sialic
      acid/apoB ratio was significantly higher in the diabetics compared to the
      controls in every LDL fraction. Fractional catabolic rate (FCR) for LDL apoB was
      significantly faster in the diabetics than in the non-diabetics, and was
      positively associated with the sialic acid ratio in the total and dense LDL. In
      multiple linear regression analyses with FCR for total and dense LDL apoB as the
      dependent variable and the presence of diabetes, body mass index, LDL
      cholesterol, triglycerides, and sialic acid/apoB ratio as the independent
      variables, LDL cholesterol and serum triglycerides were the only variables
      entering significantly to these models. The sialic acid/apoB ratio of total and
      dense LDL was similar in subjects without and with CAD. These results suggest
      that in this population the sialic acid content of LDL was not associated with
      clinical signs of atherosclerosis, but the catabolic rate of dense LDL apoB was
      positively related to the sialic acid content of the respective lipoproteins.

PMID- 8864947
TI  - Apolipoprotein E5 (Glu212-->Lys): increased binding to cell surface proteoglycans
      but decreased uptake and lysosomal degradation in cultured fibroblasts.
AB  - A new apolipoprotein (apo) E variant, apoE5 (Glu212-->Lys) was identified in a
      Turkish family. The variant was due to a point mutation (CAG-->AAG) at the first
      nucleotide position of the codon encoding amino acid residue 212 of the mature
      apoE. The 23-year-old index patient was heterozygous for the mutation.
      Examination of the proband's kindred revealed six heterozygous and two homozygous
      mutation carriers. Compared to non-carriers, carriers of the mutation had
      slightly higher triglycerides (1.25 versus 1.11 g/l) and lower HDL cholesterol
      (0.36 versus 0.41 g/l). Very low density lipoproteins (VLDL) from an apoE5
      (Glu212-->Lys) homozygote displayed enhanced binding (+17%, P < 0.05), but
      decreased uptake (-35%, P < 0.0001) and degradation (-51%, P < 0.0001) in
      cultured fibroblasts, compared to E3/3-VLDL. The region of the apoE molecule
      surrounding residue 212 contains a heparin binding domain. Consistently, the
      enhanced cell surface binding of E5/5-VLDL was observed in "wild-type" Chinese
      hamster ovary cells (+19%, P < 0.05), but not in proteoglycan-deficient cells.
      The binding of E5/5-VLDL to heparin was increased (+22%, P < 0.05). As the
      endocytosis of apoE-containing particles involves the transfer of proteoglycan
      bound ligands to lipoprotein receptors, the stronger binding of apoE5 (Glu212-
      >Lys) to proteoglycans could reduce the rate at which the mutant is finally
      delivered to endocytotic pathways. These data may provide evidence for a
      functionally important heparin binding site around amino acid residue 212 of the
      apoE molecule in vivo.

PMID- 8864948
TI  - Binding affinity and particle size of LDL in subjects with moderate
      hypercholesterolemia: relationship with in vivo LDL metabolism.
AB  - The aim of this study was to examine relationships between low density
      lipoprotein (LDL) metabolism, in vitro binding, and particle size. Twenty four
      study subjects, 17 men and 7 women, had elevated plasma total cholesterol (TC),
      ranging from 174 to 232 mg/dl, and LDL cholesterol (LDLC) ranging from 113 to 195
      mg/dl after 12 weeks on a Step I diet. The fractional clearance rate (FCR) for
      LDL ranged from 0.233 to 0.619 pools/day (0.366 +/- 0.021) and was significantly
      correlated with plasma triglycerides (TG) (P < 0.05). Although there was no
      relation between FCR and binding in the study group as a whole, those subjects
      with an FCR within the normal range (< 0.45, n = 20), showed a significant
      negative correlation between FCR and the KD for LDL binding, (r = 0.52). A subset
      of four subjects with an elevated FCR (> 0.45) had higher production rate (PR) (P
      < 0.005) and a significant positive correlation between the KD for LDL binding
      and FCR (P < 0.05). LDL size varied from 240.0 to 265.8 A and was significantly
      inversely correlated with plasma TG (P < 0.001) but there was no relation between
      LDL size and metabolism or binding affinity. Thus, there appears to be a
      correlation between binding affinity and clearance for subjects who had normal
      LDL production and clearance rates. On the other hand, mechanisms other than
      binding affinity appear to influence clearance in subjects with elevated rates of
      production and clearance.

PMID- 8864949
TI  - Factors influencing Lp[a]- particle size as determined by gradient gel
      electrophoresis.
AB  - This study examined factors influencing the particle diameter of Lp[a]-, the low
      density lipoprotein (LDL)-like moiety of Lp[a], in 26 subjects chosen to provide
      a range of Lp[a] and triglyceride levels. Lp[a] and LDL fractions were isolated
      by vertical density ultracentrifugation. Lp[a] was further purified using a
      lysine-Sepharose affinity column and Lp[a]- obtained by incubating Lp[a] with
      dithiothreitol. Lp[a], LDL, and Lp[a]- fractions were run on 3-13% gradient gels
      to determine particle diameter. Lp[a] size correlated positively with LDL size (r
      = 0.62; P < 0.001), but the association between Lp[a]- size and LDL size was
      stronger (r = 0.82; P < 0.0001). Log triglyceride level correlated inversely with
      Lp[a]- size (r = -0.72; P < 0.0001) and LDL size (r = 0.69; P < 0.0001). HDL
      cholesterol level correlated positively with Lp[a]- size (r = 0.67; P < 0.0005)
      and LDL size (r = 0.64; P < 0.0005). The strong correlation between LDL size and
      Lp[a]- size may be due to extracellular utilization of circulating LDL in the
      production of Lp[a] or may reflect the same metabolic processes influencing both
      these particles once Lp[a] has been formed.

PMID- 8864950
TI  - Effects of n-3 fatty acids on the NMR profile of plasma lipoproteins.
AB  - The effects of fish oil supplementation (14.5 g n-3 fatty acids/day) on plasma
      lipoprotein particles in healthy volunteers were assessed by high resolution 13C
      and 1H nuclear magnetic resonance (NMR) spectroscopy. Resonances not previously
      observed in the 13C and 1H spectra of plasma and isolated lipoproteins were
      detected after fish oil ingestion. The 13C resonances, centered at 14.3, 127.1,
      and 131.6 ppm, have been assigned to specific carbon groups (CH3-CH2-CH = CH-,
      CH3-CH2-CH = CH-CH2-, CH3-CH2-CH = CH-CH2-, respectively) in eicosapentaenoic
      acid (C20:5n-3) and docosahexaenoic (C22:6n-3) DHA. The new lipid resonance
      observed in the 1H spectra of plasma (0.941 ppm) is consistent with the
      incorporation of these n-3 fatty acids into lipoprotein particles. The presence
      of increased EPA and DHA in plasma lipids was confirmed by gas-liquid
      chromatography. A marked reduction in the intensity of the methylene signal from
      very low density lipoproteins (VLDL) was also observed with fish oil. This
      reduction arises from a decrease in plasma triglyceride concentration (ca. 18%)
      and a reduction in the number of VLDL particles. Transverse relaxation studies of
      isolated VLDL and low density lipoprotein (LDL) showed significant elevation in
      the T2 of the -(CH2)n- and CH3- signals from non-n-3 fatty acids. The relaxation
      characteristics and signal intensity of the novel 1H peak (0.941 ppm) point to
      the existence of n-3 enriched microenvironments within lipoprotein particles.
      These findings suggest that incorporation of EPA and DHA into VLDL and LDL, after
      fish oil ingestion, leads to significant alteration in the molecular architecture
      of lipoprotein particles.

PMID- 8864951
TI  - A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser)
      results in altered postprandial chylomicron triglyceride and retinyl palmitate
      response in normolipidemic carriers.
AB  - An Asn291Ser mutation in exon 6 of the lipoprotein lipase gene (LPL) frequently
      occurs in Caucasians (2-4%) and results in a partial catalytic defect. Although
      this mutation may be associated with low HDL cholesterol and elevated
      triglyceride levels, some carriers are normolipidemic and may have LPL activity
      in the normal range in the fasting state. To assess in vivo the influence of
      dietary stress on the function of this mutation, we have performed oral fat load
      studies on three unrelated normolipidemic Asn291Ser carriers and compared these
      results to five healthy controls and to a subject with a clear 50% reduction in
      LPL activity compared with controls. The Asn291Ser carriers exhibited a more
      pronounced postprandial response compared with non-carriers as evidenced by
      higher chylomicron triglyceride (TG) and chylomicron retinyl palmitate peaks (P =
      0.03 and P = 0.02, respectively). Significantly higher area under response curves
      were also seen for both chylomicron triglycerides (P = 0.02) and chylomicron
      retinyl palmitate (P = 0.01) when compared with non-carriers. These results
      provide further in vivo evidence for the functional effects of this common
      mutation despite normal fasting lipid levels. These data suggest that even though
      subjects with this mutation may be normolipidemic in the fasting state,
      environmental stress such as an oral fat load may unmask the catalytic defect and
      result in significant disturbances in postprandial chylomicron metabolism.

PMID- 8864952
TI  - Multiple regulatory steps are involved in the control of lipoprotein lipase
      activity in brown adipose tissue.
AB  - Lipoprotein lipase (LPL) supplies brown adipose tissue with fatty acids for
      nonshivering thermogenesis. In brown adipose tissue of the Djungarian hamster we
      studied i) the molecular mechanisms involved in cold-induced stimulation of LPL
      activity, ii) the adrenergic control of LPL expression, and iii) compared LPL
      expression in brown and white adipose tissue. i) After 8 h cold exposure we
      detected a 2-fold increase in LPL activity and protein level in brown adipose
      tissue, whereas LPL mRNA level remained unchanged. A cold-induced increase (1.5
      fold) in LPL activity was observed in brown adipose tissue of hamsters treated
      with actinomycin D prior to 4 h cold exposure, whereas cycloheximide treatment
      completely abolished LPL stimulation. Thus, these data suggest that during the
      initial phase (< 24 h) of cold exposure the stimulation of LPL activity in brown
      adipose tissue is most likely due to increased translation. In contrast, during
      prolonged cold exposure, we detected a maximal 7-fold increase in LPL activity
      and a 2- to 3-fold increase in LPL mRNA level in brown adipose tissue indicating
      LPL regulation at the pretranslational level. Furthermore, comparison of LPL
      protein and activity in brown adipose tissue during prolonged (> 24 h) cold
      exposure provides some evidence that the active fraction of the enzyme pool in
      brown adipose tissue is increased in response to cold. ii) Surgical denervation
      and noradrenaline treatment revealed a complex role of the sympathetic
      innervation in the control of LPL expression in brown adipose tissue. Denervation
      decreased LPL mRNA level, but increased LPL activity. Noradrenaline treatment
      stimulated LPL activity to a similar extent as cold exposure. However, cold
      induced stimulation of LPL activity was not impaired by denervation. iii) Cold
      exposure significantly elevated LPL mRNA content of inguinal white adipose
      tissue, although LPL activity was not affected. Posttranscriptional mechanisms
      appear to be involved in the tissue specific control of LPL expression.

PMID- 8864953
TI  - Reduced cholesteryl ester transfer in plasma of patients with lipoprotein lipase
      deficiency.
AB  - The net mass transfer of cholesteryl ester (CE) from high density lipoprotein
      (HDL) to the apolipoprotein (apo) B-containing lipoproteins, very low density
      lipoprotein (VLDL) and low density lipoprotein (LDL) in plasma (cholesteryl ester
      transfer (CET)) from three patients lacking lipoprotein lipase (LpL) activity was
      significantly lower (P < 0.001) than in plasma from fasting control subjects with
      comparable triglyceride levels. Chylomicrons isolated from LpL-deficient fasting
      plasma showed the same low level of CET activity as observed in the intact plasma
      when combined with HDL and cholesteryl ester transfer protein (CETP)-containing d
      1.063 g/ml bottom fractions from control subjects. Preincubation of chylomicrons
      and large triglyceride-rich lipoproteins (Sf > 400) from LpL-deficient plasma
      with milk LpL, however, stimulated the capacity to engage in CET 4- to 5-fold to
      the same level as chylomicrons and VLDL from control subjects after a fat load.
      Consistent with these measurements of CET activity in plasma, chylomicrons
      obtained from the LpL-deficient subjects after a 14-h fast had higher TG/CE
      ratios than chylomicrons from controls 3 h after ingesting a fat load (LpL
      deficient 26.3 +/- 9.0 vs. controls 6.9 +/- 2.1; mean +/- SD). The mass of CETP
      did not differ in LpL-deficient and control subjects (LpL-deficient 1.03 +/- 0.22
      micrograms/ml vs. controls 1.58 +/- 0.58 micrograms/ml). These studies are
      consistent with earlier in vitro studies showing that the actions of lipoprotein
      lipase and its lipolytic products are essential, for maximal cholesteryl ester
      transfer protein activity.

PMID- 8864954
TI  - Role of HDL phospholipid in efflux of cell cholesterol to whole serum: studies
      with human apoA-I transgenic rats.
AB  - Sera of transgenic rats expressing human apoA-I were tested for their ability to
      stimulate efflux of radiolabeled cholesterol from Fu5AH rat hepatoma cells.
      Expression of human apoA-I resulted in a dose-dependent increase in HDL, as
      measured by both HDL-cholesterol and HDL-phospholipid, and produced a decrease in
      rat apoA-I. In rats expressing high concentrations of human apoA-I (TgR[hAI]high,
      human apoA-I > 250 mg/dl), the increase in HDL-phospholipid was not proportional
      to the increase in human apoA-I, as illustrated by a HDL-PL/total apoA-I ratio of
      0.84 +/- 0.19 compared to a ratio of 1.28 +/- 0.29 for control rats and of 1.28
      +/- 0.39 for rats expressing low levels of human apoA-I (TgR[hAI]low, human apoA
      I < 250 mg/dl). Compared to sera from control animals, efflux of cell cholesterol
      was increased by 26% in the sera from TgR[hAI]low, and by 76% in the
      TgR[hAI]high. An examination of the relationships between efflux and HDL-related
      parameters demonstrated a hyperbolic relationship between efflux and either HDL
      cholesterol or HDL-apoA-I. In contrast, there was a strong linear association (r2
      = 0.84) between cholesterol efflux and HDL-phospholipid, indicating that this
      parameter is the component of HDL that best reflects the serum's efflux
      efficiency. The importance of phospholipids in modulating cholesterol efflux was
      further explored by measuring the effect of supplementation of serum with
      dimyristoylphosphatidylcholine (DMPC) vesicles, apoA-I, or both DMPC vesicles and
      apoA-I. Whereas addition of human apoA-I had no effect on efflux, supplementation
      with DMPC vesicles produced a substantial increase in efflux that was further
      stimulated by the combination of DMPC vesicles and apoA-I. These results
      demonstrate that a major component of HDL that modulates cell cholesterol efflux
      is phospholipid.

PMID- 8864955
TI  - Role for sterol regulatory element binding protein in the regulation of farnesyl
      diphosphate synthase and in the control of cellular levels of cholesterol and
      triglyceride: evidence from sterol regulation-defective cells.
AB  - In order to define the factors involved in the regulation of farnesyl diphosphate
      (FPP) synthase, we used sterol regulation-defective (SRD) cell lines that
      constitutively express either high (SRD-2) or low (SRD-6) levels of
      transcriptionally active sterol regulatory element binding protein (SREBP). FPP
      synthase mRNA levels were high in SRD-2 cells and low in SRD-6 cells and were
      unaffected by the addition or removal of sterols from the media. In contrast, the
      mRNA levels in parental CHO-7 cells were regulated by sterols. SRD-2, SRD-6, and
      CHO-7 cells were also transiently transfected with plasmids containing FPP
      synthase promoter-reporter genes. Reporter gene activity was significantly higher
      in SRD-2 cells than in either SRD-6 or CHO-7 cells, consistent with a higher rate
      of transcription of the reporter gene in SRD-2 cells. The high expression of the
      reporter gene in SRD-2 cells was not observed when the FPP synthase promoter
      contained a three base pair mutation within an SREBP binding site, termed sterol
      regulatory element-3 (SRE-3). These observations are consistent with the
      hypothesis that high levels of transcription of the FPP synthase gene are
      dependent on the availability of transcriptionally active SREBP. We also
      demonstrate that the incorporation of radioactive acetate into both cholesterol
      and fatty acids was enhanced in SRD-2 cells as compared to CHO-7 or SRD-6 cells.
      Finally, we demonstrate that the concentrations of cholesterol, cholesteryl
      ester, and triglyceride were all significantly elevated in SRD-2 cells. We
      conclude that SREBP is involved not only in the regulation of FPP synthase and
      cholesterogenesis but also in fatty acid and triglyceride synthesis.

PMID- 8864956
TI  - Formation of new HDL particles from lipid-free apolipoprotein A-I.
AB  - Remodelling of plasma high density lipoproteins (HDL) promotes the dissociation
      of lipid-free apolipoprotein (apo)A-I from the particles. In the present study,
      we have investigated the formation of new HDL particles from lipid-free apoA-I in
      a process dependent on the presence of nonesterified fatty acids (NEFA) and other
      lipoprotein fractions (as donors of lipid). Incubations were carried out that
      included lipid-free apoA-I, VLDL, and lipoprotein lipase (LPL) or lipid-free apoA
      I, either VLDL or LDL, and sodium oleate. Any new HDL particles that were formed
      were separated from lipid-free apoA-I in the ultracentrifuge. When any one of the
      ingredients in the incubation was absent, the apoA-I remained lipid-free;
      however, when all the ingredients were present, a significant proportion of the
      apoA-I was recovered in the HDL density fraction. This coincided with the
      formation of at least three HDL-sized subpopulations; one of the subpopulations
      was considerably smaller than HDL3c and had pre-beta 1 mobility while two were in
      the size range of human HDL2b and HDL3c and had pre-beta 2 electrophoretic
      mobility. The new HDL were predominantly discoidal in shape and their major
      constituents were apoA-I, phospholipid, and unesterified cholesterol. In
      conclusion, these results show that lipid-free apoA-I can form new HDL particles
      in the presence of NEFA and other lipoprotein fractions. The formation of pre
      beta 1 HDL from lipid-free apoA-I indicates that this process is potentially of
      great importance in terms of generating plasma acceptors of cell cholesterol in
      reverse cholesterol transport.

PMID- 8864957
TI  - VLDL receptor mediates the uptake of human chylomicron remnants in vitro.
AB  - The VLDL receptor has been described as a new member of the LDL receptor
      supergene family that specifically binds VLDL in vitro via apolipoprotein E and
      lipoprotein lipase. Both apolipoprotein E and lipoprotein lipase are constituents
      of chylomicron remnants, another triglyceride-rich lipoprotein which has been
      proposed as a physiological ligand for the VLDL receptor. We used human
      chylomicron remnants to study their uptake into LDL, receptor-deficient Chinese
      hamster ovary cells overexpressing the human VLDL receptor. The uptake into these
      cells was compared to that into cells transfected with an empty transfection
      vector. Human chylomicron remnants were produced in vitro by hydrolysis with
      lipoprotein lipase, and were labeled with 125I. The uptake of these remnants into
      the cells overexpressing the VLDL receptor was found to be about 3-fold higher
      than the uptake into the control cells. The addition of a surplus of either
      apolipoprotein E or inactivated lipoprotein lipase to the remnants led to an
      increase in particle uptake. The chylomicron remnant uptake was inhibited by
      addition of the 39 kDa receptor associated protein These in vitro experiments
      strongly support the idea that the VLDL receptor is a physiological receptor for
      chylomicron remnants. The increase of receptor-mediated uptake induced by the
      addition of apoE or lipoprotein lipase underlines the role of these two proteins
      in this process.

PMID- 8864958
TI  - Allelic variation in the gene encoding the cholesteryl ester transfer protein is
      associated with variation in the plasma concentrations of cholesteryl ester
      transfer protein.
AB  - The cholesteryl ester transfer protein (CETP) mediates the transfer of
      cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich
      lipoproteins. Mutations that abolish CETP function are associated with very high
      levels of HDL cholesterol, but the effect of more common allelic variation at
      this locus is less clear. In this study, we have measured plasma CETP
      concentration and plasma HDL cholesterol concentrations in 694 individuals from
      106 nuclear families. Robust sibling-pair methods indicated linkage between the
      CETP locus and inter-individual variation in plasma CETP concentrations. Allelic
      variation at the CETP locus accounted for 20% of the variation in plasma CETP
      concentration. No relation between allelic variation at the CETP locus and plasma
      HDL cholesterol levels was detected. These data indicate that polymorphism in the
      CETP gene confers variation in plasma CETP concentration. However, this degree of
      variation in CETP function is not systematically associated with variation in
      plasma HDL-C concentrations.

PMID- 8864959
TI  - Differential activity and lack of synergy of lung surfactant proteins SP-B and SP
      C in interactions with phospholipids.
AB  - This study shows that the hydrophobic lung surfactant proteins (SP)-B and SP-C
      are not synergistic in enhancing functionally relevant surface behaviors in films
      and dispersions with phospholipids, and that SP-B is more effective than SP-C in
      facilitating surface activity. Purified bovine SP-B, SP. C, or SP-B/C (1/1 by wt)
      were combined with chroma tographically purified calf lung surfactant
      phospholipids (PPL), or with dipalmitoyl phosphatidylcholine (DPPC) or complex
      phospholipid mixtures containing 75% or 50% DPPC (75% SPL or 50% SPL). Adsorption
      was consistently better in corresponding mixtures of phospholipids plus SP-B
      versus SP-C, but was not improved further by substitution of SP-B/C for SP-B.
      Interfacial films of DPPC or SPL plus 1.3% SP-B or 1.3% SP-C had improved
      respreading compared to phospholipids alone (Wilhelmy balance, 23 degrees C and
      37 degrees C), but substitution of mixed SP-B/C for either pure apoprotein did
      not increase respreading further. Surface-excess films of phospholipids plus SP-B
      had higher maximum surface pressures, or maintained a high maximum pressure
      through more consecutive compressions, than corresponding films with SP-C.
      Dispersions of phospholipids plus 1.3% SP-B or mixed (1/1) SP-B/C (2.6%) rapidly
      lowered surface tension to < 1 mN/m in oscillating bubble studies (20 cpm, 37
      degrees C), while corresponding dispersions containing SP-C reduced surface
      tension more slowly or reached higher minima. Mixtures of 50% SPL with SP-B
      versus SP-C were also better able to resist inhibition by serum albumin in bubble
      and adsorption studies, and inhibition resistance was not significantly improved
      in mixtures containing 2.6% SP-B/C (1/1) versus 1.3% SP-B. The lack of synergy in
      hydrophobic apoprotein function, coupled with the greater effectiveness of SP-B
      in improving phospholipid adsorption, dynamic surface activity, and inhibition
      resistance, suggests that mixtures of phospholipids plus SP-B or related peptides
      may be particularly relevant its clinical exogenous surfactants.

PMID- 8864960
TI  - A new mutation in the gene for lysosomal acid lipase leads to Wolman disease in
      an African kindred.
AB  - Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both
      autosomal recessive disorders associated with reduced activity and genetic
      defects of lysosomal acid lipase (LAL). The strikingly more severe course of WD
      is caused by genetic defects of LAL that leave no residual enzymatic activity.
      Mutations at the exon 8/intron 8 transition of the LAL gene have been identified
      in several CESD and WD patients and are responsible for the manifestation of the
      disease. We have determined the genetic defect in a 3-month-old boy of African
      origin affected by WD. No enzymatic activity of the lysosomal acid lipase was
      detectable in white blood cells and cultured fibroblasts. Analysis of his LAL
      cDNA and genomic DNA revealed that he was homozygous for a mutation at position 
      3 of the exon 8 splice donor site. A C-->T transition leads to a nonsense codon
      and to a premature termination of the LAL protein at amino acid 277. Due to this
      mutation, a shorter LAL mRNA species was also generated that lacked exon 8 and
      was deficient of the nonsense codon. As a consequence, the protein synthesis
      proceeded to the natural termination codon, but the enzyme generated had an
      internal deletion of 24 amino acids (254-277) and was also inactive. These
      findings, together with our previous observations when analyzing the mutations in
      WD and CESD patients lead to the conclusion that the more severe WD is due to
      mutations that absolutely abolish lysosomal acid lipase (LAL) enzyme activity and
      the cholesteryl ester storage disease phenotype is due to mutations that allow
      some residual LAL activity to be manifested.

PMID- 8864961
TI  - Adaptation of cholesterol absorption after proximal resection of porcine small
      intestine.
AB  - Cholesterol absorption occurs primarily in the upper small intestine. Our aim was
      to assess absorption of cholesterol during ileal adaptation after proximal small
      intestinal resection. In vivo absorption and elimination of cholesterol, plasma
      cholesterol, cholesterol precursors, and plant sterols were related to intestinal
      morphology and transit 4 (n = 5), 8 (n = 5), and 14 (n = 5) weeks after a 75%
      proximal resection of porcine small intestine, and compared to preoperative (n =
      5) and transected (n = 5) control animals. Fractional cholesterol absorption, the
      daily amount of cholesterol absorbed, plasma cholesterol, and plant sterol to
      cholesterol proportions were significantly (P < 0.05 or less) decreased, whereas
      fecal loss of cholesterol as neutral steroids, less so as bile acids, plasma
      cholesterol precursor proportions, and ileal mass and villus height were
      significantly increased (P < 0.05 or less) after 8 weeks of the resection.
      Cholesterol absorption efficiency, decreased by the resection, was gradually
      increased from 5.4 +/- 2.2 to 26.9 +/- 3.9% during the 14 postoperative weeks (P
      < 0.0001) simultaneously with a 46% increase in villus height compared with
      transection (P < 0.0001), but absorption remained still below control levels
      (80.4 +/- 2.5%, P < 0.0001). In resected and control animals, villus height
      correlated positively with cholesterol absorption efficiency (r = 0.85, P <
      0.0001; r = 0.76, P = 0.01) and plasma plant sterol proportions (r = 0.94-0.95, P
      < 0.0001; r = 0.78-0.85, P < 0.008), respectively. In conclusion, after massive
      proximal small bowel resection, adaptation of intestinal cholesterol absorption
      efficiency occurs in the distal ileum closely parlleling villus hypertrophy.

PMID- 8864962
TI  - Effects of inhibiting cholesterol absorption and synthesis on cholesterol and
      lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic
      men.
AB  - Effectiveness of a simultaneous inhibition of cholesterol absorption and
      synthesis, caused by sitostanol ester margarine and pravastatin, was studied to
      control mild hypercholesterolemia in men with non-insulin-dependent diabetes
      mellitus (NIDDM) (n = 8). Margarine, 24 g daily, was a basal dietary treatment.
      Four 7-week intervention periods included margarine, sitostanol (3 g/day) ester
      margarine, pravastatin (40 mg/day), and sitostanol ester margarine plus
      pravastatin in a random order. Pravastatin lowered serum total (-32%) and LDL
      cholesterol (-38%) and apolipoprotein B (-39%) because of enhanced removal (+20%)
      and decreased production (-26%) of LDL apolipoprotein B, and reduced synthesis (
      9%) and turnover (-8%) of cholesterol, which resulted in reduced biliary
      cholesterol seretion (-18%). Even though serum triglycerides were lowered by 28%,
      VLDL, IDL, and light and dense LDL became triglyceride-enriched. Despite
      increasing cholesterol synthesis, sitostanol lowered LDL cholesterol (-14%) by
      inhibiting cholesterol absorption (-68%) and LDL apolipoprotein B production rate
      (-20%). Combination of pravastatin and sitostanol ester lowered serum total,
      VLDL, IDL, and LDL cholesterol and LDL apolipoprotein B by the highest rate, 35%,
      50%, 35%, 44%, and 45% from the control margarine period, respectively, because
      of reduced apolipoprotein B transport rate (but unchanged removal), in both the
      total and dense LDL subfractions. HDL cholesterol and apolipoprotein A-I kinetics
      were unchanged. In spite of decreased absorption, cholesterol synthesis was not
      compensatorily increased. In conclusion, simultaneous inhibition of cholesterol
      absorption and synthesis lowers LDL cholesterol and apolipoprotein B by 44-45%
      solely through inhibition of LDL apolipoprotein B production rate in
      hypercholesterolemic NIDDM patients. A combination of statin to sitostanol ester
      margarine-resistant patients offers a safe and effective measure to normalize
      abnormally high cholesterol values, probably with a lowered statin dose.

PMID- 8864963
TI  - Functional and metabolic differences between elastase-generated fragments of
      human lipoprotein[a] and apolipoprotein[a].
AB  - We have previously shown that a functional free apolipoprotein[a] (apo[a]) can be
      isolated from its parent lipoprotein[a] (Lp[a]) by a mild reductive procedure. To
      shed further light on the properties of Lp[a] and apo[a] we subjected them to a
      limited proteolysis by porcine pancreatic elastase. This enzyme cleaved both at
      the Ile3520-Leu3521 bond in the linker between kringles IV-4 and IV-5 of apo[a]
      generating two fragments F1 and F2. In contrast to F1, which represented the N
      terminal portion of apo[a] and was functionally inert, F2, representing the C
      terminal domain, bound to lysine-Sepharose, fibrinogen, and fibronectin and
      formed a miniLp[a] particle when incubated with LDL. The proteolytic pattern by
      pancreatic elastase was also exhibited by human leukocyte elastase. F1, injected
      intravenously into normal mice, was rapidly cleared (Ty2, 2.9 h) and after 1 h
      fragments in the size range of 100-33 kDa were observed in the urine. In turn, F2
      had a longer residence time (Ty2, 5 h) and was excreted in the urine only after 5
      h as fragments of 70-45 kDa. Fragments in the same size range as found after F1
      injection were also present in the urine after injection of apo[a] or Lp[a].
      Moreover, apo[a] fragments of the size seen in mouse urine were spontaneously
      present in normal human urine and appeared derived from larger apo[a] fragments
      in the plasma. Our results indicate that enzymes of the elastase family cleave
      human apo[a] in vitro into two main fragments that differ in structural and
      functional properties and metabolic behavior. The comparable size of apo[a]
      fragments observed in the urine of humans and injected mice invites the
      speculation that enzymes of the elastase family may play a role in the biology of
      Lp[a] in vivo.

PMID- 8864964
TI  - Further characterization of the metabolic properties of triglyceride-rich
      lipoproteins from human and mouse apoC-III transgenic mice.
AB  - We previously showed that human apoC-III expression in transgenic mice causes
      hypertriglyceridemia due to the accumulation of enlarged very low density
      lipoprotein (VLDL)-like particles, with increased triglycerides and apoC-III and
      decreased apoE. In vivo turnover studies indicated the metabolic basis was
      decreased particle fractional catabolic rate. The presence of enlarged
      triglyceride-rich particles with prolonged residence time in plasma implied
      defective lipolysis, but in vitro these particles were good substrates for
      purified lipoprotein lipase (LPL). In the current study we further characterize
      the metabolic properties of these particles. We show that expression of a mouse
      apoC-III transgene can also cause hypertriglyceridemia with a similar
      accumulation of a VLDL-like particle with increased apoC-III and decreased apoE.
      A vitamin A fat tolerance test was used to show that MoCIIITg and HuCIIITg mice
      had similarly delayed clearance of triglyceride-rich postprandial particles.
      Thus, the previously observed hypertriglyceridemia caused by human apoC-III
      transgene expression was not due interspecies incompatibility but a property of
      apoC-III. In further experiments we showed VLDL from apoC-III transgenic mice
      interacted poorly with fibroblast lipoprotein receptors and this could be
      corrected by adding exogenous apoE. In addition, control VLDL interaction could
      be decreased by exogenous apoC-III. Moreover, the hypertriglyceridemia of
      HuCIIITg mice could be normalized by crossbreeding with HuETg mice. Thus, a
      functionally significant reciprocal relationship of apoC-III and apoE exists,
      presumably due to competition for space on the surface of triglyceride-rich
      lipoproteins. Finally, VLDL from HuCIITg and MoCIIITg mice showed decreased
      binding to heparin-Sepharose. This suggests and additional locus of the defect in
      these mice could potentially be in the binding of triglyceride-rich lipoproteins
      to heparan sulfate proteoglycan matrix on the surface of endothelial cells in
      which LPL is embedded. This could explain the predicted functional lipase
      deficiency in apoC-III transgenic mice based on the observation of a prolonged
      residence time of enlarged triglyceride-rich lipoproteins.

PMID- 8864966
TI  - Quantification of gangliosides by microbore high performance liquid
      chromatography.
AB  - A highly sensitive analytical method was developed that allows the separation of
      ganglioside mixtures and quantification of individual non-derivatized
      gangliosides in the concentration range between 2 pmol and 1 nmol. Gangliosides
      were separated with a gradient of acetonitrile/phosphate buffer on a 1 mm
      diameter microbore HPLC column packed with Spherisorb-NH2. They eluted according
      to their number of sialic acid residues with increasing phosphate and decreasing
      acetonitrile concentrations. The separation of different gangliosides with equal
      sialic acid content is also described. The column effluent was monitored at the
      maximum of absorption at 197 nm. The sensitivity is higher than resorcinol
      staining of fractionated gangliosides by thin layer chromatography, previously
      the standard method for ganglioside analysis. The separated gangliosides can be
      analyzed by further methods. The HPLC method described here has been applied to
      the analysis of serum and oligodendroglioma specimens.

PMID- 8864965
TI  - Effect of hypocholesterolemic doses of 17 alpha-ethinyl estradiol on cholesterol
      balance in liver and extrahepatic tissues.
AB  - This study was performed to investigate the effects of 17 alpha-ethinyl
      estradiol, a potent hypocholesterolemic agent at pharmacological doses, on
      cholesterol balance in the liver and extrahepatic tissues of the rat in vivo.
      Female Sprague-Dawley rats were treated with 17 alpha-ethinyl estradiol (5 mg/kg
      per day s.c. for 5 days) or with 4-aminopyrazolo(3,4-d) pyrimidine (20 mg/kg per
      day i.p. for 3 days). Both drug regimens suppressed plasma total and low density
      lipoprotein-cholesterol by more than 80%. Analysis of the kinetic parameters of
      low density lipoprotein transport did not show increased receptor activity in
      extrahepatic tissues during either treatment. 17 alpha-Ethinyl estradiol
      significantly increased low density lipoprotein tissue spaces and clearance rates
      in the liver, with a 5-fold increase in low density lipoprotein-receptor
      activity, whereas 4-aminopyrazolo(3,4-d)pyrimidine suppressed hepatic transport
      of low density lipoprotein probably due to a nospecific toxic effect. Treatment
      with 17 alpha-ethinyl estradiol markedly enhanced the hepatic expression of low
      density lipoprotein-receptor protein and mRNA despite a 7-fold increase in
      hepatic cholesteryl ester levels. Finally, treatment with both drugs increased
      cholesterol synthesis in several extrahepatic tissues, such as adrenals, ovaries,
      small bowel, and spleen. These findings confirm that 17 alpha-ethinyl estradiol
      at pharmacological doses markedly increases synthesis and expression of low
      density lipoprotein-receptor in the liver. Hypocholesterolemia, whether induced
      by activation of low density lipoprotein-receptors or by other mechanisms, fails
      to up-regulate low density lipoprotein transport in extrahepatic tissues, which
      rather respond by increasing local sterol synthesis. This suggests the occurrence
      of separate regulatory mechanisms for low density lipoprotein transport and
      cholesterol synthesis.

PMID- 8864967
TI  - Safety in chiropractic practice, Part I; The occurrence of cerebrovascular
      accidents after manipulation to the neck in Denmark from 1978-1988.
AB  - BACKGROUND: Problems in ascertaining cases and in determining the total number of
      treatments have made it difficult to establish the rate of cerebrovascular
      accidents (CVA) after spinal manipulative therapy. OBJECTIVES: To estimate the
      occurrence of cerebrovascular accidents after chiropractic treatment to the
      cervical spine. DESIGN: Information was sought on cases of CVA in Denmark during
      the period 1978-1988 inclusive, through several sources and through a survey of
      the Danish Chiropractors' Association. Information was sought also on proportion
      of consultations consisting of cervical treatment and preferred type of therapy.
      The incidence rate of CVA was calculated for several denominators. PARTICIPANTS:
      Targeted sample in survey 1: all 226 practicing members of the Danish
      Chiropractors' Association in 1989 [i.e., 99% of the chiropractors in Denmark at
      that time (response rate 54%)]. In survey 2, a random sample of 40 chiropractors
      (response rate 72.5%) was used. OUTCOME MEASURES: The number of CVAs in relation
      to the number of chiropractor-years, number of consultations, consultations
      including neck treatment, upper and lower neck treatment, and type of technique
      used. MAIN RESULTS: Five cases of CVA were identified; one resulted in death and
      the others in permanent neurological sequelae of varying severity. One case of
      CVA appeared for every estimated 1.3 million cervical treatment sessions and 1
      for every 0.9 million upper cervical treatment sessions. Rotation techniques were
      over-represented in relation to their estimated frequency of use. CONCLUSION:
      Although the incidence of CVA after chiropractic SMT was confirmed to be low,
      there seems to be sufficient evidence to justify a firm policy statement
      cautioning against upper cervical rotation as a technique of first choice.

PMID- 8864968
TI  - Doppler studies comparing the effects of cervical rotation and lateral flexion on
      vertebral artery blood flow.
AB  - OBJECTIVE: To determine the effects of cervical contralateral rotation and
      cervical contralateral lateral flexion on vertebral artery blood flow velocity.
      DESIGN AND SETTING: A prospective study was performed at a private chiropractic
      clinic. PATIENTS: One hundred forty-eight patients had their vertebral arteries
      insonated as part of the premanipulative screening procedure. INTERVENTION: The
      vertebral arteries were insonated using a Doppler ultrasound velocimeter in the
      neutral position, during cervical contralateral rotation to the end range and
      during contralateral lateral flexion to the end range. MAIN OUTCOME MEASURES:
      Persistence or loss of Doppler signals from the vertebral arteries during neck
      movement was recorded. RESULTS: Of 280 vertebral arteries able to be insonated,
      5% (0 < 5% < 9% at p = .99 confidence interval) had Doppler signals that stopped
      during contralateral rotation. Doppler signals from all 187 vertebral arteries
      tested during lateral flexion persisted, whereas 6 (3.2%) of this group of
      arteries had signals that ceased during contralateral rotation. CONCLUSION:
      Vertebral artery Doppler signals from patients can be greatly reduced or
      extinguished during contralateral cervical rotation. However, this is an unusual
      finding. The same phenomenon was not observed during contralateral cervical
      lateral flexion, which suggests that there may be less mechanical stress placed
      on the vertebral artery during lateral flexion.

PMID- 8864969
TI  - Error budgets: a system to characterize error source in health care
      experimentation.
AB  - OBJECTIVE: In the design of an experiment, it is important that all significant
      sources of error be identified and characterized accurately before the experiment
      is executed. For many experiments, the experiment designer is less inclined to
      ignore significant error factors when he adopts the use of an error budget in his
      experiment design process. A plan for generating an accurate error budget is
      presented along with a discussion concerning the disposition of significant error
      sources. METHODS: Specific methods discussed to generate the error budget are the
      fishbone diagram, factor weighing and Pareto analysis. Specific dispositions
      suggested are to eliminate, attenuate, characterize or to simply acknowledge the
      error with no remedy. These procedures, adhered to by most successful experiment
      design teams in industry, have evolved over recent decades and seem to be of use
      as they are applied to health care research. RESULTS: Use of the outlined method
      forces the experimenter to become familiarized with the most significant
      variables of the experiment he or she is designing through the deliberate
      examination of experimental noise contributors and through the comparison of the
      experimental noise to the magnitudes of the measurements in the experiment.
      CONCLUSION: The design of health care research experiments may be streamlined by
      incorporating the methods outlined in the generation of an error budget and by
      properly using the error budget to dispose of each source of error properly.

PMID- 8864970
TI  - The biomechanical significance of herniated lumbar intervertebral disk: a
      clinical comparison analysis of 22 multiple and 39 single segments in patients
      with lumbar intervertebral disk herniation.
AB  - OBJECTIVE: To analyze the clinical significance of herniated lumbar
      intervertebral nucleus pulposus (HNP) inside the spinal canal. STUDY DESIGN: This
      was a comparison study between patients with multiple lumbar disk herniation and
      those with single lumbar disk herniation receiving conservative treatment.
      METHODS: Four indices, including computed tomography, plain and dynamic radiology
      and quantified physical examinations, were compared among 22 consecutive patients
      with multiple disk protrusions and 37 with single disk protrusion before and
      after a period of conservative treatment, mainly using spinal manipulation.
      RESULTS: There were no obvious changes of HNP size, position and volume, even
      after clinical improvement. However, structural and functional recovery in the
      group with multiple segments was less satisfactory than that of the group with
      single segment involvement. CONCLUSIONS: The protruded disk tissue plays an
      important role in the biomechanical disturbances of the spinal column besides
      that of an irritating agent to nerve root(s).

PMID- 8864972
TI  - The role of transcranial Doppler sonography in the identification of patients at
      risk of cerebral and brainstem ischemia.
AB  - OBJECTIVE: To review the literature pertaining to transcranial Doppler (TCD)
      examination of the anterior and posterior cerebral circulation. This paper
      focuses on the application of TCD as a screening modality for vertebral artery
      induced brainstem ischemic events. DATA SOURCES: A Medline literature search was
      performed. Key terms included; transcranial Doppler, vertebral artery dissection,
      neck trauma, stroke and vertebrobasilar system. DATA EXTRACTION: The studies
      examined TCD techniques that monitor the hemodynamics of the circle of Willis.
      Papers pertaining to vertebral artery trauma and resulting brainstem injury were
      included. The validity and reproducibility of these procedures were also
      reviewed. CONCLUSION: TCD procedures provide hemodynamic data pertaining to intra
      arterial vertebrobasilar stenosis and extra-arterial mechanical compression of
      the vertebral arteries. During cervical spine positional testing, brainstem
      symptoms may be correlated with TCD documented perfusion deficits. TCD increases
      the sensitivity of the standard positional test.

PMID- 8864971
TI  - A normal sagittal spinal configuration: a desirable clinical outcome.
AB  - OBJECTIVE: Traditional forms of chiropractic treatment methods have attempted to
      restore alignment of vertebrae to proposed "normal" positions. Although this
      approach has existed throughout chiropractic's 100-yr history, little has been
      written in the scientific literature in support of this approach. The objective
      of this review is to study further the rationale behind this approach and
      evaluate some of the mechanical, anatomical and physiological evidence upon which
      this chiropractic approach is based. STUDY SELECTION: Articles and studies were
      selected that discuss analysis of stress and strains in spinal tissues from
      gravitational loading and experimental deformation in human and animal models.
      Studies that included radiographic measurements and classifications of spinal
      configuration in the sagittal plane were reviewed for their relevance to the
      chiropractic concept of a typical, usual or normal spinal configuration against
      which to compare patients. CONCLUSION: The usual, typical or normal configuration
      of the cervical spine in the sagittal dimension is a lordosis with a range of
      16.5-66 degrees when measured as tangent lines along the cervical curve of the
      posterior vertebral body margins of C2 and C7. An analysis of stresses and
      strains supports this claim, as do studies from the scientific literature that
      attempt to measure and classify average cervical configuration from large
      population bases. The use of normative data as a gauge against which to measure
      patients' structural health and as an outcome of the degree of success or failure
      of chiropractic interventions seem to be logical consequences of these findings.

PMID- 8864973
TI  - Does 'normal' vision improve with spinal manipulation?
AB  - OBJECTIVE: To discuss a patient whose spinal abnormalities may have caused
      subliminal visual field loss. CLINICAL FEATURES: A 22-yr-old man suffered from a
      painful neck. His vision was in the normal range, as measured by computerized
      static perimetry. INTERVENTION AND OUTCOME: To define a guideline for a proposed
      investigation into visual field changes with spinal adjustment, his visual fields
      were tested before and after a normal office spinal manipulation. After this
      procedure, there was a measurable rise in the visual sensitivity of both eyes.
      CONCLUSION: The use of computerized static perimetry changes to measure the
      cerebral effects of spinal manipulation is recommended for future chiropractic
      research.

PMID- 8864974
TI  - A rationale for case-finding for thyroid disease in a chiropractic setting with
      illustrations from the LACC experience.

PMID- 8864975
TI  - Chiropractic and rural health; the role of chiropractors in the delivery of
      interdisciplinary health care in rural settings.

PMID- 8864976
TI  - Basal metabolic temperature vs. laboratory assessment in "posttraumatic
      hypothyroidism".

PMID- 8864977
TI  - Evaluation of anti-human antibodies for immunohistochemistry on archival nonhuman
      primate tissues.
AB  - A panel of commercially available antibodies which recognize specific antigens on
      human tissues was developed for use in immunohistochemistry on tissues from eight
      species of nonhuman primates. Antibodies were selected for potential usefulness
      in diagnostic pathology, and for effectiveness in formalin-fixed, paraffin
      embedded tissues. Tissues from four species of macaques and four New World
      monkeys were evaluated. Using these antibodies we were able to identify 17/21
      antigens examined in all eight species, and 21/21 antigens in the four species of
      macaques. Detailed immunohistochemistry protocols are presented, along with a
      systematic approach to developing a protocol for a new antibody.

PMID- 8864978
TI  - SIVagm incidence over two decades in a natural population of Ethiopian grivet
      monkeys (Cercopithecus aethiops aethiops).
AB  - The incidence of SIVagm seropositivity in a natural population of Ethiopian
      grivet monkeys (Cercopithecus aethiops aethiops) is investigated using plasma
      samples collected in 1973, and shown to be similar to that reported from the same
      population in 1990-91. Results tend to support our previous conclusions: endemic
      SIVagm has little or no impact on the survival of wild grivet monkeys, and the
      virus is transmitted almost always by sexual contact, occasionally by trauma, and
      rarely if ever maternally. Small differences between 1973 and 1990-93 suggest
      that the stress of drought years may raise the incidence of traumatic
      transmission, and temporarily depress transmission by sexual activity, in this
      population.

PMID- 8864979
TI  - Functional immaturity in neonatal polymorphonuclear leukocytes of rhesus monkeys.
AB  - Despite major advances in the management and care of critically ill and low-birth
      weight human and nonhuman primate infants over the past two decades, infection
      remains a major source of neonatal morbidity and mortality. Although the causes
      of enhanced susceptibility and dissemination of neonatal infections are
      incompletely defined in the literature, substantial evidence from this and other
      laboratories has implied that functional abnormalities of neonatal
      polymorphonuclear leukocytes (PMNs) may be a major contributor. Increased
      understanding of the functional characteristics of neonatal PMNs should,
      therefore, provide significant insight into the pathogenesis and possible therapy
      of infections in neonates. Our laboratory has been actively involved in
      evaluating the functional competence of PMNs in neonatal human and nonhuman
      primates. This report describes a study in which we have confirmed and
      characterized the functional compromises in neonatal PMNs of rhesus monkeys,
      including deficiencies in chemotaxis, membrane deformability, phagocytosis, and
      killing.

PMID- 8864980
TI  - Cell surface marker evaluation of infant Macaca monkey leukocytes in peripheral
      whole blood using simultaneous dual-color immunophenotypic analysis.
AB  - Cross-reactivity between several commercially available mouse antihuman
      monoclonal antibodies (mAbs), conjugated to phycoerythrin (PE) and fluorescein
      isothiocyanate (FITC) fluorochromes, and peripheral blood leukocyte surface
      antigens, has been established in infant cynomolgus (Macaca fascicularis) monkeys
      using whole blood lysis, and two-color, PE and FITC flow cytometric analysis.
      With the exception of the CD8 marker, the bivariate dot-plot patterns for all
      other markers were similar in infant monkeys and in humans. For the CD8 marker,
      however, a CD8+CD2- population of cells was observed in the majority of monkeys
      tested (10 out of 12). The number of CD8+CD2- cells was higher (13%) in infant
      monkeys compared to the 3% reported for adult human blood. The mean percentage
      and absolute numbers for the cell surface markers identified with the human mAbs
      CD2 (FITC, Ortho, Paritan, NJ), CD4 (PE, B-D, Mountain View, CA), and CD8 (PE, B
      D) when these were combined with a series of PE- or FITC-labelled human mAbs were
      similar across all combinations tested. Statistically significant differences
      were observed between male and female monkeys for the mean percentage levels of
      CD4 (females > males) and for the CD4/CD8 ratio (females > males). Such gender
      differences need to be taken into consideration when infant cynomolgus monkeys
      are used as models for chemical-induced immunotoxicity studies. Measurement of
      the interleukin-2 (IL-2) and transferrin proved to be useful in monitoring in
      vitro cellular activation in infant cynomolgus and possibly in rhesus (M.
      mulatta) monkeys.

PMID- 8864981
TI  - Assessment of early placental development in the cynomolgus monkey (Macaca
      fascicularis) using colour and pulsed wave Doppler sonography.
AB  - Colour flow mapping and pulsed wave Doppler were used to assess the process of
      placental growth and development in the cynomolgus monkey from 32 to 71 days
      gestational age. Fetal and maternal vessels were reliably visualised and
      insonated. Accurate longitudinal non-invasive assessment of placentation is
      possible using this technique.

PMID- 8864982
TI  - Tracking of dye-labeled lymphocytes in rhesus macaques.
AB  - Lymphocytes were isolated from rhesus monkeys and marked with a fluorescent
      lipophilic dye to monitor their distribution in vivo. Dye-labeled cells were
      either monitored by blood draws over a three-month period, or identified within
      peripheral organs upon autopsy. Lymphocyte labeling conditions were optimized.
      Dye-labeled lymphocytes could be detected in the circulation for at least 100
      days by flow cytometry and fluorescence microscopy. Activated lymphocytes were
      removed from the circulation more rapidly than lymphocytes that had not been
      activated.

PMID- 8864984
TI  - Baylisascaris larva migrans in a spider monkey (Ateles sp.).

PMID- 8864983
TI  - Development of the definitive kidney in the cynomolgus monkey (Macaca
      fascicularis).
AB  - Formation of the definitive kidney in Macaca fascicularis embryos was
      investigated using light and electron microscopy. Appearance of the definitive
      kidney at stage 14 was indicated by the ureteric bud invading the metanephrogenic
      blastema. Glomerular capillaries originate from the connective tissue that
      surrounds the developing renal vesicle. At 46-100 days gestational age the more
      developed glomeruli show thinning of the capillary endothelium, thickening of the
      basal membrane, and presence of pedicels, suggesting a capability of renal
      function.

PMID- 8864985
TI  - Hepatocellular carcinoma in a squirrel monkey (Saimiri sciureus).
AB  - A well-differentiated hepatocellular carcinoma of the liver was diagnosed in a
      female squirrel monkey. The lesion showed trabecular, solid and glandular
      features that are characteristics of malignant liver tumours.

PMID- 8864986
TI  - Glioblastoma multiforme arising in the irradiated spinal cord of a rhesus monkey
      (Macaca mulatta).
AB  - An adult female rhesus monkey that had received 44.0 Gy of cobalt 60 radiation to
      8 cm of the cervical and upper thoracic spinal cord approximately 2.8 years
      postirradiation developed a sudden onset of self-mutilation and loss of function
      of the right arm followed progressively by loss of function of the left arm and
      terminally bilateral paresis of the legs. Histopathologic examination of the
      cervical spinal cord revealed a glioblastoma multiforme that extended from the
      cervical medullary junction to the sixth cervical vertebrae. Because of the
      infrequent occurrence of spontaneous neoplasia in rhesus monkeys and the location
      in the radiation field, the glioblastoma is believed to be radiation induced.

PMID- 8864987
TI  - Modulation of protein release from chitosan-alginate microcapsules using the pH
      sensitive polymer hydroxypropyl methylcellulose acetate succinate.
AB  - The release characteristics of protein from chitosan-alginate microcapsules
      prepared using an electrostatic droplet generator were evaluated. The release
      studies were undertaken in-vitro in simulated gastrointestinal fluids covering
      the pH range 1.2-8. Chitosan-alginate microcapsules showed unsatisfactory release
      properties, losing 94% of the encapsulated proteins (bovine serum albumin) over a
      24 h period at pH 1.2. Incorporation of a pH-sensitive polymer, hydroxypropyl
      methylcellulose acetate succinate (HPMCAS), in the microcapsules, by coating the
      capsule membrane as well as blending with the capsule core polymer in varying
      ratios, produced significant changes in the release profiles of the
      microcapsules. At pH 1.2, the modified microcapsules retained up to 60% of the
      encapsulated protein after 24 h. The results obtained highlight the potential of
      HPMCAS as a release-modifier in chitosan-alginate microcapsules.

PMID- 8864988
TI  - Microencapsulation of ovalbumin in poly(lactide-co-glycolide) by an oil-in-oil
      (o/o) solvent evaporation method.
AB  - The objective of this study was to produce biodegradable poly(lactide-co
      glycolide) (PLGA; 50/50) microspheres by an oil-in-oil (o/o) solvent evaporation
      method to prolong the in vitro release of ovalbumin (OVA) as a model protein. The
      effects, on loading efficiency, microsphere yield, morphology and drug release,
      of two dispersing agents, aluminium tristearate and Span 80, in mineral oil were
      examined. PLGA 50/50 microspheres containing OVA powder (sieved through a 53
      microns mesh) were prepared using an o/o solvent evaporation method. When
      aluminum tristearate was employed as a dispersing agent, the loading efficiency
      and yield of OVA had maximum values of 89 and 72% at 0.15% (w/v) aluminum
      tristearate, respectively. Morphology studies suggested that the obtained
      microspheres were spherical, and had a smooth surface. The diameters of the
      microspheres ranged between 100 and 200 microns. The loading efficiency, or
      yield, for microspheres decreased significantly above or below 0.15% (w/v)
      aluminum tristearate, and microspheres with irregular shapes were observed. The
      minimum sedimentation volume ratio (F) was obtained at a dispersity of carbon
      black particles in ethanol containing 0.15% (w/v) aluminum tristearate by a
      sedimentation study, and the cloudy supernatant suggested a deflocculated
      suspension. However, on the contrary, when Span 80 was added into the mineral oil
      as a dispersing agent, the concentration of Span 80 had little or no effect on
      the characteristics of the prepared microspheres. Drug loadings (60-70%) were
      obtained within the Span 80 concentrations employed in the present study (0.05
      1.0% (w/v)). The yields were also in the same levels. The microspheres prepared
      in mineral oil containing Span 80 had an average diameter less than 50 microns in
      all cases. Sustained-release characteristics were demonstrated for PLGA
      microspheres prepared in mineral oil containing aluminum tristearate as a
      dispersing agent, even though a burst release at the initial phase was observed.
      This initial burst release from PLGA microspheres was reduced to some extent by
      micronization of the OVA powder using a planetary-type ball mill. However, PLGA
      microspheres prepared in mineral oil containing Span 80 as a dispersing agent,
      exhibited a large initial burst release. This burst release seems to be due to
      the smaller size of microspheres and the OVA powder adhering to the surface of
      PLGA microspheres (confirmed by scanning electron microscope (SEM) study).

PMID- 8864989
TI  - Microencapsulation of an iron chelator for sustained release and crystal habit
      modification.
AB  - DMHP (1,2-dimethyl-3-hydroxy-pyrid-4-one) is an orally-active iron chelator that
      has a short biological half-life and hence a sustained-release formulation is
      currently being developed. DMHP exists as needle-like crystals that cannot be
      size-characterized accurately for pharmaceutical manufacturing. The current study
      was undertaken to simultaneously achieve crystal-habit modification and provide
      sustained-release properties using a microencapsulation technique. Eudragit-RS, 
      RL, -L90 and Cellulose Acetate Phthalate were used in a phase-separation method
      to produce discrete, spheroidal, free flowing microcapsules of DMHP that could be
      sized readily. The obtained microcapsules were evaluated for drug content, size
      distribution, micromeritic properties, and in-vitro dissolution in gastric
      followed by intestinal pH environments at 37 degrees C. In-vitro dissolution
      studies revealed that DMHP release from the microcapsules can be retarded for up
      to 10 h. Changes in polymer type, polymer content, and processing parameters
      resulted in drastic changes in the microencapsulation process, and release
      characteristics of the microcapsules.

PMID- 8864990
TI  - Microencapsulation of allopurinol by solvent evaporation and controlled release
      investigation of drugs.
AB  - The microencapsulation of drugs is gaining importance in many research
      activities. A common technique for preparing microcapsules is the solvent
      evaporation method which is simple but has a large number of reaction control
      parameters. This study reports the microcapsulation of allopurinol by the solvent
      evaporation method and the release of the drug from the microcapsules. The effect
      of concentration of poly(vinyl alcohol) (as a surfactant), molecular weight of
      ethyl cellulose and stirrer speed in the preparative method were studied. The
      effect of molecular weight of ethyl cellulose and particle size on drug release
      were also investigated. It has been found that the drug release is decreased with
      increasing molecular weight of polymer and increasing particle size.

PMID- 8864991
TI  - In-vivo studies in the treatment of oral ulcers with liposomal dexamethasone
      sodium phosphate.
AB  - Liposomes are man-made organelles composed of bimolecular lipid layers enclosing
      aqueous compartments. Dexamethasone Sodium Phosphate (DSP) was encapsulated in
      MLV liposomes and served as the test solution. DSP in solution served as control.
      Both were labeled with 99mTc. The rats were divided into three groups: typical
      application group, intramucosal injection and control group. Oral mucosal ulcers
      were produced by silver nitrate and was monofocal. Rats were killed at three and
      24 h, respectively, after application. Ulcerated mucosa, intact adjacent mucosa
      and distant mucosa were excised. Biodistribution was determined by radiotracer
      technique in the three mucosal parts as well as in the blood, liver, spleen and
      brain. Liposomes increase local and decrease systemic drug concentration. Another
      finding was that liposomes localize the drug in the ulcerated area. In
      conclusion, liposomes may be useful in the treatment of oral ulcers.

PMID- 8864992
TI  - Effect of formulation and processing factors on the characteristics of
      biodegradable microcapsules of zidovudine.
AB  - Biodegradable microcapsules of zidovudine (AZT) were prepared using poly
      (lactide/glycolide) by the solvent evaporation technique. The objective of this
      project was to focus on the effect of several formulation and processing factors
      on the efficiency of encapsulation, surface morphology, and drug release
      profiles. When the drug was incorporated as powder or as aqueous suspension
      containing a high amount of insoluble particles, to the organic phase the surface
      of the microcapsules was appeared to be wrinkled. The efficiency of encapsulation
      decreased when AZT powder was dispersed directly into the organic solvent instead
      of adding as an aqueous solution. When the relative volume of the aqueous phase
      containing 1% PVA was changed from 25 up to 125% of the volume of the organic
      phase, the efficiency of encapsulation, surface morphology, and release profiles
      did not change significantly. The efficiency of encapsulation decreased from 9 to
      3.8% when the drug loading was increased from 10 to 50% of the weight of the
      polymer.

PMID- 8864993
TI  - Interfacial/free radical polymerization microencapsulation: kinetics of particle
      formation.
AB  - Microcapsules containing pigment and polymer were prepared by dispersing a
      viscous mixture of pigment, core monomers, initiators and oil-soluble shell
      monomer in an aqueous solution of surfactants, forming oil-in-water droplets.
      Subsequently, a water-soluble shell monomer was added to these droplets,
      encapsulating them via interfacial (IF) polycondensation. These microcapsules
      were then heated for free radical (FR) polymerization of the core monomers.
      Effects of primary variables, such as the shearing time during particle
      formation, surfactant concentration, organic phase concentration, and mode of
      water-soluble shell monomer addition, were studied. The results indicated that
      polyvinylalcohol (PVOH), used as the surfactant/stabilizer, reacted with the oil
      soluble shell monomers. The depletion of PVOH, especially when PVOH concentration
      was low, resulted in rapid growth of particle size and, eventually, suspension
      failure. The kinetic data revealed a particle formation mechanism which consists
      of two processes. The first process is the formation of an equilibrium particle
      size by the equilibrium process of particle breakage due to the mechanical
      shearing force and coalescence due to collisions among particles and surface
      tension forces. The second process is the reaction between PVOH and oil-soluble
      shell monomer which leads to the depletion of PVOH and consequently causes more
      coalescence of particles and a significant increase in the equilibrium particle
      size. The net effect of these two processes shows an optimum shearing time where
      the smallest particle size can be attained, and this optimum time is a function
      of several primary variables. Methods to prevent the reaction and therefore the
      depletion of PVOH are proposed.

PMID- 8864994
TI  - The Microsponge Delivery System (MDS): a topical delivery system with reduced
      irritancy incorporating multiple triggering mechanisms for the release of
      actives.
AB  - The Microsponge Delivery System (MDS) is a unique technology for the controlled
      release of topical agents and consists of macroporous beads, typically 10-25
      microns in diameter, loaded with active agent. When applied to the skin, the MDS
      releases its active ingredient on a time mode and also in response to other
      stimuli (rubbing, temperature, pH, etc). MDS technology is being used currently
      in cosmetics, over-the-counter (OTC) skin care, sunscreens and prescription
      products. By delivering the active gradually to the skin, MDS-benzoyl peroxide
      formulations, for example, have excellent efficacy with minimal irritation. These
      are typical benefits from the use of the MDS.

PMID- 8864995
TI  - Effect of vehicle on topical liposomal drug delivery: petrolatum bases.
AB  - Liposornes used for topical applications are often incorporated into a vehicle to
      achieve suitable viscosity and application properties. The effect of
      incorporation of liposomes into white petrolatum as a possible dermatological
      base was investigated. A number of formulae were developed to determine the type
      of petrolatum base that would be compatible with the liposomes. The physical
      appearance and stability of the vaseline-liposome (VL) preparations were
      determined by organoleptic analysis and microscopy. The effect of petrolatum base
      on the drug release from the liposomes was determined in a flow-through diffusion
      cell system using a model silastic polymer membrane as barrier. A base containing
      white petrolatum 46.7% (w/w), stearyl alcohol 6.7% (w/w), cholesterol 13.3 (w/w),
      Tween 80 16.7% (w/w) and Span 16.7% (w/w) was selected for diffusion studies,
      since the mixture of this base and liposome preparation, at 1:1.9 (w/w) ratios,
      provided a stable, dermatologically acceptable dosage form, in which the
      liposomes were uniformly distributed and their structures were preserved.
      Diffusion studies showed that the drug release rate decreases 2.5x when the
      liposomes are incorporated into the vaseline base; however, after a temporary
      decrease they seem to extend the duration of release beyond that of the original
      liposomal formula. These studies revealed a possibility of using white petrolatum
      in the topical application of liposomes.

PMID- 8864996
TI  - Effect of gelation conditions and dissolution media on the release of paracetamol
      from alginate gel beads.
AB  - Paracetamol was entrapped in alginate beads gelled with calcium or zinc at 0.1,
      0.34 or 0.7M. The payloads were of the order of 60-70% w/w which represented an
      entrapment yield of > 75%. The release of drug from the beads was observed in
      three media; water, Simulated Gastric Fluid USP without pepsin (SGF) and 0.1%
      trisodium citrate solution. Release was slowest in water and was complete within
      4-5 h. The zinc beads released more slowly than calcium beads prepared at the
      same molar concentration of cation. Complete release of drug from the alginate
      gel beads in SGF occurred within 2 h and was unaffected by the cation type and
      concentration. Except for beads prepared from 0.1M zinc, paracetamol was released
      rapidly in the citrate solution. All release profiles could be described by first
      order kinetics with half-lives which ranged from 25-73 min. Due to the rapid
      release in acidic conditions, it is unlikely that alginate beads loaded with a
      relatively water soluble drug will provide satisfactory prolonged release orally.

PMID- 8864997
TI  - The potential of topoisomerase I inhibitors in the treatment of CNS malignancies:
      report of a synergistic effect between topotecan and radiation.
AB  - Despite innovations in imaging, surgery, and radiation therapy, local failure
      remains the principle clinical problem in most CNS malignancies. To date,
      chemotherapy has not major impact in the treatment of most adult CNS tumors. The
      inroads made by chemotherapy in pediatric CNS malignancies suggest that novel
      drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I)
      inhibitors are a relatively new group of chemotherapy drugs with a novel
      mechanism of action. Drugs in this group currently undergoing clinical trials are
      the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is
      substantial preclinical and some clinical evidence to suggest that these drugs
      could be useful in the treatment of CNS malignancies. Preclinical studies with
      the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic
      activity in a variety of CNS malignancies. In addition, Topotecan has good CNS
      penetration in primates, and recent preliminary phase I and II clinical trials of
      Topotecan in pediatric and adult CNS malignancies have been promising. In this
      paper, we describe the unique mechanism of action, antineoplastic activity, and
      radiosensitizing properties of Topo I inhibitors. We present the first report
      demonstrating potentiation of radiation lethality by Topotecan in a human glioma
      (D54) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there
      is evidence to suggest that Topo I inhibitors may be beneficial in the treatment
      of CNS neoplasms on the basis of their antineoplastic activity alone, as well as
      their radiosensitizing effects. Two clinical trials which utilize concurrent
      Topotecan and radiation in the treatment of pediatric and adult CNS malignancies
      are discussed.

PMID- 8864998
TI  - Predicted and actual BCNU concentrations in normal rabbit brain during
      intraarterial and intravenous infusions.
AB  - Normal New Zealand White rabbits were used to compare theoretical brain
      concentrations (based upon pharmacokinetic modeling) with actual experimental
      concentrations of BCNU following intraarterial (IA) or intravenous (IV)
      infusions. IA infusion therapy for brain tumor patients has been promising based
      upon theoretical predictions but of limited effectiveness clinically.
      Experimentally-measured rabbit carotid artery flow rates (63.9 +/- 3.4 ml/min)
      [mean +/- 1 sem] and BCNU systemic clearances (197 +/- 10.2 ml/min) predicted a
      theoretical IA advantage of 4.1 +/- 0.2. Ipsilateral brain concentrations of BCNU
      during and after IA infusions (20 mg/min/m2 over 15 minutes) were: 16.2 +/- 2.9,
      19.0 +/- 3.9, 20.3 +/- 2.8, 4.8 +/- 2.5, 2.1 +/- 1.5, and 1.7 +/- 1.6
      micrograms/gm brain at 5, 10, 15, 25, 35, and 45 minutes after infusion start.
      Mean concentrations at same time points in contralateral hemisphere (IA
      infusions) were: 7.1 +/- 1.8, 9.0 +/- 1.8, 10.3 +/- 0.7, 4.2 +/- 1.4, 2.2 +/-
      1.2, 2.0 +/- 1.5 micrograms/gm brain. Concentrations in either hemisphere during
      IV infusions were similar to contralateral hemisphere during IA infusions.
      Comparison of ipsilateral: contralateral hemisphere ratios during and after IA
      infusions were: 3.2 +/- 0.4, 2.6 +/- 0.3, 2.2 +/- 0.3, 1.1 +/- 0.3, 1.0 +/- 0.4,
      and 0.9 +/- 0.3 at the same time points. Although these data show higher drug
      concentrations with IA infusions, actual values were considerably less than
      predicted by theoretical modeling. This discrepancy between theoretical and
      experimental results emphasizes need for further study of causes and remedies so
      that IA therapy can achieve better drug concentrations with less toxicity.

PMID- 8864999
TI  - Loss of heterozygosity of microsatellite loci on chromosome 9p in astrocytic
      tumors and its prognostic implications.
AB  - We analyzed 19 samples of various astrocytic tumors (3 astrocytomas, 5 anaplastic
      astrocytomas, and 11 glioblastomas) for loss of heterozygosity (LOH) on
      chromosome 9p at 6 microsatellite loci (D9S54, IFNA, D9S171, D9S104, D9S165, and
      D9S166). Polymerase chain reaction was performed and the products were
      electrophoresed on polyacrylamide gel. As many as 16 of the 19 samples (84%)
      exhibited LOH. Three of the 7 informative loci (43%) showed LOH at D9S54, 7 of 17
      (41%) at IFNA, 8 of 14 (57%) at D9S171, 7 of 14 (50%) at D9S104, 4 of 8 (50%) at
      D9S165, and 2 of 7 (29%) at D9S166. LOH was recognized in 57% of the informative
      loci in anaplastic astrocytomas and 54% in glioblastomas, while it was seen in
      only 8% of the astrocytomas. Accumulation of LOH with progression or recurrence
      of tumor was seen in 2 patients. Although, the survival period of the patients
      correlated well to the histological types of astrocytic tumors, we could not find
      any obvious correlations between the presence/absence of LOH and the survival
      period in these patients. In conclusion, we speculate that LOH on chromosome 9p
      is involved in malignant progression of astrocytomas, but has no significance in
      predicting survival period in these patients.

PMID- 8865000
TI  - A strategy for selective anti-cancer drug concentration increase in rat glioma
      tissue with Ca(2+)-channel blocker co-administration: calcium kinetics in intra
      glioma arteriolar smooth muscle cells.
AB  - A rat glioma model was employed to estimate the Ca2+ kinetics in the tumor
      arteriolar smooth muscle cells. Electron microcytochemistry revealed that the
      density of intracellular Ca2+ deposits in the intra-tumor arteriolar smooth
      muscle cells was significantly greater, with slightly higher membrane Ca(2+)
      adenosine triphosphatase (ATPase) activity, compared to the contralateral
      cerebral arterioles. Furthermore, the administration of tyrphostin, a tyrosine
      kinase inhibitor, specifically increased only the intra-tumor blood flow. These
      findings suggest that the condition of the intra-tumor arteriole alters the
      susceptibility to contraction by the accelerated Ca2+ influx into the cytoplasm
      mediated through the tyrosine kinase pathway. After the administration of
      diltiazem, which also has a blocking effect on the Ca(2+)-channel mediated
      through this pathway, the local intra-tumor blood flow showed an increase of 39%
      with a marked decrease of intracellular Ca2+ concentration of the arteriolar
      smooth muscle cells in the tumor, while the blood flow in the basal ganglia
      increased by only 8%. The intra-tumor concentration of Nimustine-HCl (ACNU) with
      co-administration of diltiazem was significantly increased compared to that
      without the co-administration. Co-administration of diltiazem may be a valuable
      strategy in chemotherapy for glioma in affording the selective increase of intra
      tumor concentration of the anti-cancer drug.

PMID- 8865001
TI  - DNA ploidy and S-phase in recurrent astrocytomas: a retrospective study by flow
      cytometry of deparaffinized specimens.
AB  - Twenty-two patients with recurrent astrocytic tumors were treated surgically two
      or even three times. At the time of the first surgery 6 tumors were fibrillary
      astrocytomas (grade II), 9 anaplastic astrocytomas (grade III) and 7
      glioblastomas (grade IV). Histopathological specimens from second surgery
      demonstrated in 12 cases signs of higher grades of malignancy. Flow cytometry
      (FCM) did not reveal any significant changes of S-phase fraction (p = 0.55). This
      study supports the theory that, given enough time, the histopathology of brain
      tumors change significantly from more benign forms to more malignant ones. The
      flow cytometry (FCM) could trace a weak tendency to higher S-phase fractions at
      the time of the second surgery. No apparent change of ploidy pattern was
      observed. In spite of the unequivocal histopathological changes of the recurrent
      astrocytomas the flow cytometry failed to indicate similar changes in terms of
      ploidy and S-phase fraction parameters.

PMID- 8865002
TI  - Unusual early recurrence of a cerebellar pilocytic astrocytoma following complete
      surgical resection. Case report and review of the literature.
AB  - Pilocytic cerebellar astrocytomas are usually benign tumors with generally an
      excellent prognosis following complete surgical resection. The goal of surgery is
      total resection to minimize the risk of recurrence. In this case report, a 5-year
      old boy who had undergone total resection of a posterior fossa pilocytic
      cerebellar astrocytoma (as documented by a contrast-enhanced computed tomography
      (CT) scan within 24 hours following surgery), developed a massive recurrence of
      the tumor within four months. Both the initial histology and the sections
      examined after the second resection revealed features typical for a pilocytic
      astrocytoma with no suspicion of malignancy. This case is unusual in that it is
      contrary to other reports suggesting that CT-documented complete surgical
      resection of pilocytic astrocytomas is without recurrence, and suggests the need
      for vigilant radiographic and clinical follow-up of these patients even if
      apparent complete resection of the tumor has been achieved.

PMID- 8865003
TI  - Resolution of recurrent malignant ganglioglioma after treatment with cis-retinoic
      acid.
AB  - Ganglioglioma is an uncommon brain tumor with glial and neuronal cellular
      components and a somewhat benign course. We are presenting an unusual case of
      ganglioglioma with malignant transformation in both cellular components
      associated with an aggressive clinical course. An almost complete resolution of
      the recurrent progressing tumor was achieved after treatment with cis-retinoic
      acid (cRA) as a single agent. A possible differential effect of cRA on the
      neuronal component of the tumor is suggested.

PMID- 8865004
TI  - Cognitive dysfunction following surgery for intracerebral glioma: influence of
      histopathology, lesion location, and treatment.
AB  - This study examined the relationship between cognitive function, tumor
      malignancy, adjunctive therapy, and lesion lateralization following surgery for
      intracerebral glioma. Neuropsychological test battery results showed no
      difference between patients with highly malignant gliomas and those with less
      malignant gliomas, but differences were found for tumor lateralization and type
      of therapy. Scores on a test of graphomotor speed were lowest for patients who
      had received radiation or a combination of radiation and chemotherapy, regardless
      of lesion location. Other test results did not differ according to type of prior
      treatment but were related instead to tumor lateralization. Left hemisphere
      lesions were associated with lower scores on verbal tests, while right hemisphere
      lesions were related to lower scores on a test of facial recognition. These
      findings suggest that neuropsychological tests may be useful for distinguishing
      between the diffuse side effects of brain tumor therapy and the focal effects of
      tumors and surgery on brain functions. In addition, it appears that any
      differences in cognitive function due to tumor malignancy are eliminated or
      reduced following surgical intervention.

PMID- 8865005
TI  - Quality of life in brain tumor patients.
AB  - With the aim of evaluating the quality of life (QL) of 101 brain tumor patients,
      a multidimensional approach was adopted, using the Functional Living Index-Cancer
      (FLIC) as a global measure of well-being, the Karnofsky Performance Scale (KPS)
      and the Index of Independence in Activity of Daily Living (ADL) as indices of
      physical and functional dimensions, the State-Trait Anxiety Inventory (STAI) and
      the Self-Rating Depression Scale (SRDS) for psychological assessment, and
      neuropsychological tests for abstract reasoning, attention, memory and frontal
      lobe functions. The patients were grouped on the grounds of disease stage and
      treatment. The FLIC and KPS ratings increased from the patients who had just
      undergone surgery to patients who were disease-free after completing chemotherapy
      and radiotherapy, thus showing that the QL may improve during the disease despite
      aggressive treatments, providing there is no tumor recurrence. However, only the
      FLIC consistently discriminated the patients' stratification. The ADL revealed no
      between-group differences, whereas the STAI and SRDS revealed the presence of
      emotional troubles at the beginning and at the end of treatment. Cognitive
      impairment was more serious after radiotherapy and chemotherapy, as well as in
      patients with tumor recurrence. The FLIC significantly correlated with all of the
      other scales used, showing that it is useful in summarizing both the physical and
      psychosocial impairment of brain tumor patients. Of the pathological variables, a
      tumor location in the anterior right hemisphere or diencephalon was associated
      with high FLIC ratings, may be due to the minor cognitive impairment observed in
      patients with these tumor sites. Of the demographic variables, the level of
      education was associated with high FLIC ratings, thus highlighting the role of
      psychosocial environment in improving the QL. The use of a multidimensional
      approach or a global index of well-being that also reflects psychosocial and
      cognitive aspects proved to be more appropriate than traditional functional
      instruments (such as the KPS) in assessing the QL of brain tumor patients and in
      detecting the extent of the disease.

PMID- 8865007
TI  - Luxury perfusion following anterior ischemic optic neuropathy.
AB  - We present five patients who developed luxury perfusion following anterior
      ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as
      "capillary hemangioma" or neovascularization of the disc. In each case, the
      segment of disc hyperemia corresponded to a spared region of visual field. Luxury
      perfusion represents a reparative autoregulatory reaction to ischemia.

PMID- 8865008
TI  - Acute zonal occult outer retinopathy and central nervous system inflammation.
AB  - This case report describes a patient who developed the characteristic features of
      acute zonal occult outer retinopathy (AZOOR), but whose case was unusual because
      of macular involvement, recurrences, and association with an inflammatory CNS
      disorder. The patient was followed for > 7 years; clinical examinations,
      electroretinography, electro-oculography, cerebrospinal fluid evaluations, and
      magnetic resonance imaging (MRI) were used to document the recurrent AZOOR and
      CNS disorder. The patient first presented with entoptic symptoms and a scotoma
      referable to dysfunction of her peripapillary and peripheral right retina. At
      that time, she also had asymptomatic involvement of her peripheral left retina,
      cerebrospinal fluid pleocytosis, and multiple brain MRI signal abnormalities.
      During the next several years, she developed recurrences of AZOOR, which first
      affected her right macula and later involved her peripheral left retina. Visual
      electrophysiological studies confirmed impairment of outer retinal function. The
      patient developed her first neurological symptom, acute relapsing-remitting
      cervical myelitis, > 6 years after her visual presentation. Her clinical course,
      laboratory studies, and neurodiagnostic evaluations were consistent with CNS
      inflammation, but they were not typical of multiple sclerosis. Since AZOOR is a
      newly recognized disorder, its full clinical spectrum may not yet be established
      and could include CNS involvement.

PMID- 8865006
TI  - Estramustine in malignant glioma.
AB  - Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen
      mustard, has primarily been employed in the treatment of advanced prostatic
      carcinoma. However, a significant amount of preclinical investigation has been
      directed toward estramustine's activity against human malignant glioma. These
      studies have demonstrated that estramustine has potent antiproliferative effects
      against malignant glioma both in vitro and in vivo. Similar antimitotic effects
      also have been demonstrated for other carbamate esters. Estramustine does not
      impair proliferation of nonneoplastic astrocytes at concentrations that inhibit
      glioma cells. Although the reasons for this selective activity remain to be
      determined, it has been shown that malignant gliomas expresses an estramustine
      specific binding site, estramustine-binding protein, more than brain tissue. In
      the clinical situation, an uptake and accumulation of estramustine in human
      glioma tissue have been demonstrated. Estramustine has been shown to enhance the
      cytotoxic effects of irradiation in relatively radioresistant glioma cells both
      in cell culture and in a rat glioma model. Estramustine has been regarded as
      mainly an anti-mitotic drug but recently other effects such as inhibition of DNA
      synthesis, induction of apoptosis, and membrane alterations have been shown. This
      report summarizes the preclinical observations concerning the effects of
      estramustine and related compounds on human malignant gliomas. These findings
      form the basis for proposing further laboratory and clinical investigation
      regarding estramustine and human malignant gliomas.

PMID- 8865009
TI  - Peripapillary fluorescein leakage in 11778 Leber's optic neuropathy.
AB  - A 17-year-old young man presented with a 2-month sequential visual loss in both
      eyes. Vision was 20/200 in the right eye and 20/400 in the left eye. Both discs
      were hyperemic with circumpapillary telangiectasia and nerve fiber swelling.
      Fluorescein angiography revealed a fuzzy hyperfluorescence due to leakage from
      dilated capillaries on both discs in the late transit. Molecular mitochondrial
      DNA study confirmed a homoplasmic 11778 Leber's optic neuropathy.

PMID- 8865010
TI  - Bilateral optic neuropathy associated with influenza vaccination.
AB  - We report a 61-year-old woman with bilateral optic neuritis and loss of vision
      following influenza vaccination. The patient had good recovery of vision
      following steroid treatment.

PMID- 8865012
TI  - Primary optic pathway sarcoidosis in a 38-year-old white man.
AB  - We report a case of primary optic pathway sarcoidosis in a 38-year-old white man.
      The disorder was limited to the optic nerves and was resistant to
      corticosteroids.

PMID- 8865011
TI  - Neuro-ophthalmologic findings in the Asperger disorder.
AB  - Asperger disorder is a complex behavioral disorder that may be related to autism.
      We examined a 49-year-old man with Asperger disorder who had multiple neuro
      ophthalmologic abnormalities, including colobomatous defects involving the optic
      discs and peripapillary retina, and abnormal ocular motility with an
      oculocephalic dyskinesia. Asperger disorder may be associated with a variety of
      neuro-ophthalmologic disturbances.

PMID- 8865013
TI  - Ocular motor consequences of damage to the abducens nucleus area in humans.
AB  - A patient with a complete unilateral conjugate gaze paralysis caused by a small
      lesion affecting the region of the right abducens nucleus, documented by magnetic
      resonance imaging, is reported. Eye movements were quantitatively evaluated using
      electro-oculography. A gaze-evoked nystagmus to the contralateral side and
      impairment of smooth pursuit and vestibular ocular reflex in the contralateral
      hemifield of movements were found. The differential diagnosis of conjugate gaze
      paralysis and the additional ocular motor abnormalities are interpreted in light
      of clinical and experimental findings.

PMID- 8865014
TI  - Convergence nystagmus associated with spasmus nutans.

PMID- 8865015
TI  - Intrasellar vascular malformation mimicking a pituitary macroadenoma.
AB  - We report the case of a 61-year-old man with an unusual intrasellar vascular
      malformation, who presented with symptoms of hypopituitarism and whose
      neuroradiologic evaluation mimicked a pituitary macroadenoma. The histopathologic
      and radiologic findings are discussed. This rare lesion should be considered in
      the diagnosis of a sellar mass lesion.

PMID- 8865016
TI  - Cavernous sinus syndrome in Hodgkin's disease.
AB  - Hodgkin's disease has not been reported to produce an isolated cavernous sinus
      syndrome, although this phenomenon is well-described in non-Hodgkin's lymphoma.
      We review the 16 cases of cavernous sinus syndrome caused by non-Hodgkin's
      lymphoma and report two patients with Hodgkin's disease in clinical remission who
      developed recurrent disease in the cavernous sinus. MRI revealed a mass lesion in
      the left cavernous sinus in each patient. Corticosteroids and radiation therapy
      were effective palliative measures. In both patients, recurrence in the cavernous
      sinus preceded other systemic evidence of recurrent Hodgkin's disease.

PMID- 8865017
TI  - Pseudotumor associated with CNS lymphoma.
AB  - A 42-year-old immune-competent woman with orbital pseudotumor and presumed
      intracranial extension into the temporal lobe responded well clinically and
      radiologically to high-doses of corticosteroids. Five months later, she developed
      worsening headaches and recurrence of the temporal lobe lesion. Biopsy revealed a
      central nervous system (CNS) lymphoma with severe reactive gliosis abutting an
      area of subarachnoid lymphocytic infiltrate.

PMID- 8865018
TI  - The anterior visual pathways--Part II.

PMID- 8865019
TI  - Simultaneous, multiple cranial neuropathies in patients with diabetes mellitus.

PMID- 8865020
TI  - Isolated third-nerve palsy associated with frontal sinus mucocele.

PMID- 8865022
TI  - Impaired stretch reflex and joint torque modulation during spastic gait in
      multiple sclerosis patients.
AB  - The modulation of the short latency stretch reflex of the soleus muscle during
      walking was investigated in seven spastic multiple sclerosis (MS) patients and
      nine healthy control subjects. Ankle joint stretches were applied by a system
      which can rotate that ankle joint in any phase of the step cycle during treadmill
      walking. The torque related to the muscle fibres contracting prior to the stretch
      and the passive tissues around the ankle joint were measured as the "non-reflex
      torque". At the same time the short latency stretch reflex-mediated EMG response
      was measured. The findings show that the stretch reflex modulation was impaired
      in spastic patients during walking. The stretch reflex modulation was quantified
      by a modulation index of an average 50% (range -5 to 100%) in the patients and
      93% (78-100%) in the control subjects (P < 0.05). The passive stiffness of the
      ankle joint was at the same time increased in the patients (P < 0.05). It is
      proposed that the impaired modulation of the stretch reflex along with increased
      ankle joint stiffness contribute to the impaired walking ability in spastic MS
      patients.

PMID- 8865021
TI  - Multiple sclerosis: symptomatic treatment.
AB  - Reports of new therapeutic agents designed to suppress inflammatory processes in
      multiple sclerosis have excited much interest but, thus far, have had little
      influence on symptoms, disability and handicap in patients. The clinical
      application of recent advances in physical, pharmacological and surgical
      approaches to management will, at least in the medium-term future, therefore
      offer significantly greater opportunities for improving the quality of life of
      patients with multiple sclerosis. Here, symptomatic treatment of the whole range
      of difficulties encountered by patients with multiple sclerosis is reviewed in
      the context of the multidisciplinary strategy crucial to an optimal outcome.

PMID- 8865023
TI  - Cardiac output in patients with acute stroke.
AB  - It is well known that blood pressure is elevated during acute stroke. Despite its
      importance for cerebral haemodynamics, cardiac output (CO) has been determined
      only in individual cases during acute stroke. We measured CO and blood pressure
      in patients with no history of heart disease who suffered from acute stroke (n =
      30) and in a control group comparable with regard to age, gender and cardiac
      health (n = 30). CO, blood pressure and heart rate were significantly (P < 0.01)
      higher in the group of stroke patients than in the control group. There was a
      tendency for more time to have elapsed between the onset of symptoms and
      measurements, the higher the CO [b = 0.08 l/min per hour (-0.01; 0.17)]. Adjusted
      for age in a multiple regression model, the regression coefficient was
      significant (CO = 10.35 +0.094 x time -0.077 x age). The present study shows for
      the first time that patients with a healthy cardiovascular system who suffer from
      acute stroke have a higher CO than a group of comparable controls.

PMID- 8865024
TI  - Fasciculations: clinical, electromyographic, and ultrasonographic assessment.
AB  - Widespread fasciculations are an important clinical sign in, for example,
      degenerative lower motor neuron diseases (LMND). Usually they are detected by
      clinical inspection and electromyography. Recently myosonography has been
      proposed for the detection of fasciculations. This prospective study compares the
      value of these three modes of examination in patients with degenerative LMND.
      Seventy healthy control persons and 34 patients (11 women, 23 men; aged 43-78
      years; median age 60.5) with LMND were included in the study. All participants
      were subjected to thorough visual screening for the presence of fasciculations.
      Fourteen muscles were examined bilaterally by myosonography and a median of 8
      muscles were screened electromyographically (only in the patients); the
      investigators were blinded to the other findings. Clinical inspection and
      ultrasonography exhibited fasciculations in up to 5 and 8 muscles, respectively,
      in 8 healthy persons. Ultrasonography demonstrated fasciculations in all
      patients, clinical inspection in all but 2, and electromyography in 26 of 33
      patients (1 patient was not examined electromyographically). Comparing the three
      methods, clinical observation revealed fasciculations in 42%, electromyography in
      39%, and ultrasonography in 67% of all muscles. Thus, ultrasonography was
      significantly more sensitive than the other techniques (P < 0.001). The
      interrater agreement (correlation coefficient) r in respect of the presence or
      absence of fasciculation was 0.71 for the clinical, 0.85 for the
      electromyographic and 0.84 for the myosonographic examinations. Ultrasonography
      and electromyography were more reliable than the clinical examination (P < 0.001
      and P < 0.01, respectively). Our study indicates that ultrasonography is more
      sensitive than clinical and electromyographic examination in visualizing
      fasciculations in patients with LMND. Additionally, it is more reliable than
      clinical examination.

PMID- 8865025
TI  - Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment.
AB  - Six patients with Hashimoto thyroiditis (HT) and associated encephalopathy (HE)
      are described and compared with 14 well-documented cases retrieved from the
      literature. HE typically affects patients when they are euthyroid and, in an
      appropriate clinical situation, antithyroid autoantibodies are the main
      indicators of HE. Since clinical features of HE are unspecific, other aetiologies
      such as infectious, metabolic, toxic, vascular, neoplastic, and paraneoplastic
      causes have to be excluded. Our own six cases and those from the literature show
      that two types of initial clinical presentation can be differentiated: a
      vasculitic type with stroke-like episodes and mild cognitive impairment in nine
      patients, and a diffuse progressive type with dementia, seizures, psychotic
      episodes or altered consciousness in 11 patients. These types may overlap,
      particularly in the long-term course without treatment. Response to steroids was
      usually excellent with complete remission in 80%. Eighteen of the 20 patients
      were women. Characteristic, though unspecific, findings were abnormal EEG (90%)
      and CSF (80%). Together with quantitative neuropsychological testing, these
      proved sensitive for monitoring the efficacy of therapy. Conversely, antithyroid
      autoantibody titres did not correlate with the severity or type of clinical
      presentation. The link between HE and HT is not clear. A pathogenetic role for
      antithyroid autoantibodies in the central nervous system seems unlikely.

PMID- 8865026
TI  - SPECT findings in an unusual case of visual hallucinosis.
AB  - A 64-year-old right-handed man acutely developed elementary visual hallucinations
      (monochromatic, moving geometrical figures), visual illusions (distortion of the
      right side of faces) with achromatopsia and blurred vision restricted to the left
      visual hemi-field. CT of the brain before and after administration of contrast
      medium and a repeat examination 2 months later showed no abnormalities, while
      brain mapping (power analysis of EEG) demonstrated theta wave slowing of the
      curve over the posterior part of the right hemisphere. 99mTC HMPAO SPECT of the
      brain, however, demonstrated an area of definite focal hypoperfusion in the right
      occipito-temporal region. Echo-Doppler-duplex and continuous wave examination of
      the cervical arterial blood vessels disclosed bilateral discrete atheromatous
      plaques that did not affect the blood flow. Transoesophageal echocardiography
      demonstrated slight mitral valve insufficiency. Cerebral angiography showed an
      occlusion of the right posterior cerebral artery. After the visual hallucinations
      had subsided, SPECT showed partial normalization of the right occipito-temporal
      perfusion. In the absence of CT evidence for a structural lesion in the
      clinically suspected areas, only functional imaging revealed an obviously
      significant lesion. This case furthermore demonstrates that SPECT can contribute
      to the identification of the pathophysiology underlying visual hallucinosis.

PMID- 8865027
TI  - The role of cognitive impairment in the quality of life after ischaemic stroke.
AB  - Many patient- and disease-related factors influence the quality of life (QL)
      after stroke. Few studies address the direct relation between cognition and
      quality of life. The objective of this study was to investigate the role of
      cognitive impairment in the QL of patients after stroke. We evaluated several
      variables including age, degree of paralysis, cognitive deficits and volume of
      infarcts, in 129 patients (64 men, 65 women; mean age 63.2, SD 14.6 years), who
      had been hospitalized a mean of 2.3 (range 0.25-4) years previously with
      ischaemic stroke. Cognitive function was assessed with the CAMCOG and QL with a
      visual analogue scale (VAS). Ninety-seven patients (75%) of our sample completed
      all the tests. Univariate analysis showed that substantial infarct volume,
      aphasia, impaired motor function, disability relating to activities of daily
      life, disturbed global functional health and impaired cognitive function were
      significantly associated with poorer QL. Age, sex and education of the patient,
      co-morbidity and location of the infarcts were not related to QL. Linear
      regression analysis revealed that disturbed global functional health, larger
      volume of infarcts and severity of aphasia were significant independent
      explanatory factors for poorer QL (adjusted R2 = 22%). In conclusion, we did not
      find a significant impact of cognitive impairment on the patients' QL. However,
      this conclusion is restricted to a relatively well group of stroke survivors.

PMID- 8865029
TI  - Disturbance of time perception in left hemispheric migraine aura.

PMID- 8865028
TI  - T-lymphocyte immunointerferon receptors in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of
      the central nervous system (CNS), associated with an altered immunoregulation.
      Interferon (IFN)-gamma, also known as immune IFN, is a cytokine with several
      effects on the immune system. Specific IFN-gamma receptors have been found on
      human lymphocytes, as well as on other cell types (e.g. gliocytes), even in the
      CNS. The aim of the present study was to evaluate IFN-gamma binding on peripheral
      blood T-lymphocytes from MS patients, compared with those from healthy subjects.
      Thirty-two patients were selected according to the classical criteria for
      definite MS; as controls, 21 healthy subjects were studied. We have found that T
      lymphocytes from MS patients bear a significantly smaller amount of IFN-gamma
      receptors than those from controls [Bmax: 568, 18 vs 708, 14 (mean, SE)
      receptors/ cell]. Such IFN-gamma binding sites are of the same type in patients
      and healthy subjects [Kd: 1.0, 0.05 vs 0.9, 0.02 (mean, SE) nM]. These findings
      are discussed in terms of immunopathogenesis of MS, since it has been reported
      that activated T-lymphocytes have decreased amounts of IFN-gamma receptors.

PMID- 8865030
TI  - Painful bilateral abducens nerve palsy associated with anti-neutrophil
      cytoplasmic autoantibodies.

PMID- 8865031
TI  - Cold-induced neuromyotonia.

PMID- 8865032
TI  - Reversible oral-facial dyskinesia in a patient receiving ciprofloxacin
      hydrochloride.

PMID- 8865033
TI  - Dual detection of antibody to both herpes simplex and varicella-zoster viruses in
      cerebrospinal fluid: cross reactivity or dual infection?

PMID- 8865034
TI  - MRI of elephantiasis neuromatosa.

PMID- 8865035
TI  - Normative data in pediatric orthopedics.

PMID- 8865036
TI  - Glenoid version in children.
AB  - Computed tomographic scans and magnetic resonance images of 111 normal shoulders
      of children were reviewed to determine the normal glenoid version in the
      pediatric age population. Glenoid version varies with age in this population. The
      glenoid is most retroverted during the first 2 years of life (-6.3 +/- 6.5
      degrees) and by the end of the first decade of life reaches adult glenoid version
      (-1.7 +/- 6.4 degrees). The difference between mean glenoid version in early life
      and mean glenoid version at the end of the first decade of life was statistically
      significant (p = 0.0013). Our value determined for adult glenoid version agrees
      with previous published data in the orthopedic and anthropologic literature. This
      study provides the normal baseline data for glenoid version in the pediatric age
      group.

PMID- 8865037
TI  - Ulnar nerve instability in children.
AB  - We carried out a cross-sectional study to define the prevalence of ulnar nerve
      instability and its relationship to ligamentous laxity in the pediatric
      population. Children were divided into three age groups: group I (0-5 years),
      group II (6-10 years), and group III (11-18 years). Of children in group I 17.7%,
      of children in group II 7.7%, and 5.7% of children in group III had dislocating
      ulnar nerves. With the exception of one patient, nerve instability was bilateral.
      Of those children possessing all five Wynne-Davies signs of ligamentous laxity,
      25.4% had dislocating nerves, 71.9% had subluxing nerves, and 2.6% had stable
      nerves. Age, ulnar nerve instability, and ligamentous laxity were statistically
      associated (p < 0.0001).

PMID- 8865038
TI  - A simplified technique for determining foot progression angle in children 4 to 16
      years of age.
AB  - Foot progression angle was determined in 400 normal children ranging in age from
      4-16 years using a new clinically available assessment technique. Children ages 4
      5 were found to have an average out-toeing of 2.8 degrees (1 STD = 6.9 degrees).
      The average foot progression angle increased with age to 7.3 degrees at age 16 (1
      STD = 4.4 degrees). Univariate analysis of these data found that age, tibial
      alignment, arch index, and the ratio of body weight to body height significantly
      affected foot progression angle. If, for children 4-16 years of age, two standard
      deviations from the average of 4.2 degrees out-toeing is taken as a normal range
      of variance, -8 degrees (in-toeing) to +16.4 degrees (out-toeing) would be
      acceptable for these ages. The measurement technique is described in detail, and
      the normative values and age-specific results are reviewed and discussed.

PMID- 8865039
TI  - Growth and development of the distal radius and ulna.
AB  - Deformities of the wrist and forearm may result from growth disturbance of the
      radius and ulna. Normal growth patterns were established by measuring the
      distance between the distal radial and ulnar growth plates in 244 children. The
      subjects were healthy, well-nourished, middle-class Americans, mostly of
      Northwest European descent. After the age of 5 years, the distance between the
      distal radial and distal ulnar growth plates progressively decreased from a mean
      of 6 mm to a mean of zero by age 13 in girls and age 15 in boys. These
      measurements are helpful in determining the normal appearance of the wrist during
      growth and in the early detection of growth discrepancy.

PMID- 8865040
TI  - Stress fractures in skeletally immature patients.
AB  - Stress fractures are a common injury in an active population. As children become
      increasingly involved in organized sports, the recognition of stress fractures
      and differentiation from infections or neoplasms requires a knowledge of their
      most common sites, presentation, and clinical course. We retrospectively reviewed
      34 stress fractures in 32 skeletally immature patients from June 1977 to May
      1993. Age, fracture location, treatment, time to union or healing, associated
      conditions, complications, radiographs, and clinical outcome were recorded. Fifty
      percent of patients were involved in sports; the most common complaint was pain
      with activity. The most common site was the tibia (47%) followed by the fibula
      (21%) and femur (12%). All had resolution of symptoms and returned to normal
      activity. All but two healed with either activity modification or cast
      immobilization. The radiographic findings included early periosteal callus
      formation that rapidly consolidated to new bone on serial studies. A careful
      history, physical examination, and radiographs can help diagnose most common
      stress fractures in the skeletally immature individual and can differentiate
      stress fractures from infection or neoplasm with appropriate conservative
      treatment.

PMID- 8865041
TI  - Role of intentional abuse in children 1 to 5 years old with isolated femoral
      shaft fractures.
AB  - We reviewed 42 children, aged 1-5 years, with isolated femoral shaft fractures to
      investigate the possible role of intentional injury in these children. Those
      children with documented motor vehicle accidents or pathologic fractures were
      excluded. Follow-up from the Department of Social Services regarding the
      potential for the fractures being inflicted was obtained. The average age of the
      children was 3.1 +/- 1.2 years; the fracture was spiral in 28. oblique in six,
      and transverse in eight; history of a fall was present in 34 and absent in eight.
      The history was considered suspicious for intentional injury in 14 children. In
      all 42 children, only one fracture was documented to be inflicted; one other
      child had prior documentation of intentional injury. From this review, the
      likelihood of intentional injury to the femoral shaft appears to be low;
      unfortunately, there were no discriminating clinical parameters to help to
      determine which injuries were intentional. The clinician should continue to have
      a high index of suspicion and have the circumstances investigated if concern
      exists regarding the fracture.

PMID- 8865042
TI  - Infantile dislocation of the elbow complicating obstetric palsy.
AB  - This is a report of three cases of complete dislocation of both the radius and
      ulna at the elbow in infants born with obstetric palsy. All three patients had
      painless elbow-flexion contractures. The pathologic anatomy included (a) medial
      and posterior displacement of the radius and ulna on the humerus, (b) laxity of
      the lateral capsule and collateral ligaments, (c) contracted medial capsule and
      collateral ligaments, (d) contracted biceps and triceps muscles, and (e)
      hypoplasia of the capitellum, trochlea, coronoid process, and olecranon fossa.
      Open reduction was attempted in all three of these patients and was successful in
      two.

PMID- 8865043
TI  - The treatment of supracondylar fractures in children with an absent radial pulse.
AB  - The purpose of this study was to determine the outcome of patients with a
      supracondylar fracture and an absent radial pulse. All children with displaced
      extension-type supracondylar fractures from 1984-1992 were eligible. Of 326
      children with supracondylar fractures, 22 had an absent radial pulse on
      admission. Fifteen of the 22 children had a well-perfused hand after closed
      reduction and K-wire fixation. Five had no pulse but a well-perfused hand after
      reduction and immobilization of the elbow in slight flexion; none had any problem
      at final review. Seven patients who had a cold white hand after closed reduction
      received open reduction of fracture and arterial exploration. In conclusion, the
      initial treatment for children with displaced supracondylar fractures with an
      absent radial pulse should be closed reduction, K-wire fixation, and
      immobilization in < 90 degrees of flexion. Children who have a well-perfused hand
      but an absent radial pulse after satisfactory closed reduction do not necessarily
      require routine exploration of the brachial artery.

PMID- 8865044
TI  - Treatment of posttraumatic cubitus varus in the pediatric population with humeral
      osteotomy and external fixation.
AB  - Cubitus varus may occur after supracondylar humerus fractures. Poor fixation,
      however, complicates operative treatment of cubitus varus. We discuss the use of
      external fixation in the treatment of cubitus varus. Five patients had humeral
      osteotomies with external fixation. The preoperative humeroulnar angle (HUA)
      averaged -24.2 degrees. The immediate postoperative HUA averaged 12 degrees, and
      the final angle averaged 13 degrees. Duration of external fixation averaged 8.9
      weeks. Complications were one transient radial neurapraxia, one superficial pin
      infection, and one keloid. No loss of correction or motion occurred with external
      fixation; we recommend external fixation as safe and effective.

PMID- 8865045
TI  - Flexible intramedullary nailing as fracture treatment in children.
AB  - To correct angulation and to avoid plaster immobilization in diaphyseal fractures
      in childhood, intramedullary nailing with flexible titanium pins is an easy and
      safe method. Under radiographic control, fractures of femur, tibia, and humerus
      are stabilized with two crossing pins. Forearm fractures are splinted with a
      single pin each in the radius and the ulna. Even displaced fractures of the
      radial neck can be corrected with a distally introduced titanium pin. This method
      is safe in elective trauma surgery and will especially be useful in
      polytraumatized children in whom multiple fractures should be stabilized with
      minimal x-ray exposure in a short time.

PMID- 8865046
TI  - Neurologic complications of pediatric femoral nailing.
AB  - Neurologic complications of femoral rodding with interlocking nails were
      investigated in 35 consecutive pediatric patients, aged 10-17 years, with
      traumatic femur fractures. We examined various risk factors for neurologic
      complications, including timing and duration of surgery, preoperative and
      intraoperative traction type, adequacy of preoperative traction, intraoperative
      patient position, degree of comminution of the fracture, and use of interlocking
      screws. There were eight (22.2%) neurologic complications. Of these, only two
      (5.6%) persisted for longer than a week. The combination of surgical delay > 48
      h, preoperative shortening, and the use of boot traction increased the incidence
      of all palsies to 5.68 times and peroneal palsies to 11.4 times that of patients
      without this combination of risk factors. Adequate pre- and intraoperative
      skeletal traction, especially in patients with hours of surgical delay, may
      decrease the incidence of neurologic complications in pediatric femoral nailings.

PMID- 8865047
TI  - The use of external fixators in femur fractures in children.
AB  - Between 1988 and 1993, 81 children with 82 femur fractures were treated with
      external fixators at the Santobono Children's Hospital of Naples. This technique
      was reserved for children older than 6 years with open fractures, multiple
      fractures, multiple trauma, and unstable fractures. The patients were placed in
      skin traction on admission, and after 24-48 h, the external fixator was applied
      under general anesthesia. Therefore, within 1 week the children were able to take
      care of themselves and to attend school. The fixator was very well tolerated and
      was removed 8-9 weeks later. The fractures healed with good alignment, no
      complications with few cases of superficial infections, and less overgrowth. The
      use of external fixation is recommended for its simplicity and lack of
      complications.

PMID- 8865048
TI  - Open fractures of the tibia and femur in children.
AB  - Forty-seven children with 32 open tibial fractures, 11 open femoral fractures,
      and six closed tibial fractures with compartment syndrome, which were surgically
      opened, were assessed for the time to union and incidence of nonunion and
      infection. Treatment varied with fracture severity and patient age. Tibial
      external fixators were supplemented by short-leg casts, and fixators were removed
      at an average of 7 weeks. No child required further surgery to achieve union.
      There was one (2%) delayed union and no nonunions. Three fractures (6%) developed
      infections. No pin-tract infections occurred in tibial fractures treated with
      external fixation with casting. The relation between age and time to union was
      statistically significant. In open fractures without segmental bone loss or soft
      tissue loss requiring major reconstruction, bony healing can be expected within 6
      months.

PMID- 8865049
TI  - Severe (type III) open fractures of the tibia in children.
AB  - Twenty children with acute type III open fractures of the tibial metaphyses or
      diaphysis were retrospectively studied. The average age was 9 years, 1 month
      (range, 2 years, 11 months to 16 years, 2 months). There were seven type IIIA
      fractures, 10 type IIIB fractures, and 3 type IIIC fractures. All fractures were
      irrigated and debrided, and prophylactic antibiotics were given for a minimum of
      48 h. Fifteen fractures were initially treated with external fixation, three with
      casts, one with internal fixation, and one with a combination of external
      fixation and limited internal fixation. Free muscle flaps were used for soft
      tissue coverage in six patients, and a local muscle flap in one patient. The
      average time to fracture healing was 29 weeks, and the median time to fracture
      healing was 20 weeks (range, 8-104). Four patients had delayed union, and two
      additional patients had nonunion. Both patients with nonunion were successfully
      treated with autologous bone grafting. The time to fracture union was related to
      the severity of soft-tissue injury, fracture configuration, segmental bone loss,
      and infection. Osteomyelitis developed in three patients. All were successfully
      treated. Two patients treated with external fixation had leg-length discrepancies
      of > 1 cm, with the injured extremity longer in both cases. There were no late
      amputations. Children with severe open fractures of the tibia have a good
      prognosis for limb salvage with aggressive wound care and fracture management.

PMID- 8865050
TI  - Open fractures of the tibia in children.
AB  - We treated 38 patients from 4 to 15 years old and with open growth plates for
      open fractures of the tibia. The average follow-up was 33 months (range, 9-122).
      All patients had repeated operative debridement, parenteral antibiotics, and
      immobilization by cast or fixation. Outcomes were analyzed with respect to age at
      the time of injury, grade of injury, and type of immobilization. The time to
      union was prolonged and averaged 21 weeks (range, 6-82). No patients younger than
      11 years required bone grafting for union. The deep infection and nonunion rate
      was 8%, with all of these occurring in patients older than 11 years. Clinically
      significant leg-length discrepancy or functional limitation was encountered only
      in patients with an ipsilateral femur fracture or with deep infection requiring
      osseous debridement. Our data suggest that open tibia fractures in children older
      than 11 years have nonunion and infection rates that parallel those of adult
      patients, but that younger children have a more benign course. With aggressive
      wound care and adequate stabilization, few complications or sequelae should occur
      in open tibial shaft fractures in younger patients.

PMID- 8865051
TI  - In-line skating fractures in children.
AB  - Seventy-eight fractures are reported in 61 children who fell while in-line
      skating. Distal radius or radius and ulna fractures as a result of falls on the
      outstretched hand occurred in > 75% of cases. Almost half of the patients were
      novices with < 4 weeks of experience on in-line skates. In fact, one in eight
      children sustained a fracture during the first attempt at the sport. Closed
      reductions were needed in 26 cases. Only two of 61 children were wearing any
      protective equipment at the time of the fracture.

PMID- 8865052
TI  - Open reduction and internal fixation of pediatric forearm fractures.
AB  - Twenty-six skeletally immature patients with 27 displaced, diaphyseal forearm
      fractures treated by open reduction and internal fixation were reviewed. The mean
      age of the patients at the time of injury was 11.5 years (range, 4-15).
      Indications for surgery included open fractures (10), unacceptable closed
      reduction (14), and loss of reduction (three). Anatomic or near anatomic fixation
      was achieved with either compression plates or intramedullary wires. The average
      time to union was 3.5 months. The average length of follow-up was 39 months
      (range, 9-98). All but three patients regained full range of motion equal to that
      of the uninjured extremity. Three complications occurred, including one deep
      infection resulting in delayed union, one nonunion with failure of hardware, and
      one proximal radioulnar cross-union. We conclude that open reduction and internal
      fixation is indicated and can be safely performed in children with open or
      unstable or both-bone forearm fractures when closed treatment methods have
      failed. Fixation is reliably achieved with compression plating or intramedullary
      nailing.

PMID- 8865053
TI  - Open reduction and internal fixation of forearm fractures in children.
AB  - We retrospectively reviewed 16 children younger than 13 years with 17 fractures
      of the shafts of the radius or ulna or both who had undergone an open reduction
      internal fixation (ORIF). ORIF was performed when a closed reduction was deemed
      unacceptable in 14 radius fractures and for three unstable open fractures of the
      radius. The average age was 9.4 +/- 2.3 years (range, 5.0-12.5). Of the 14
      fractures with an unacceptable closed reduction, soft-tissue interposition was
      encountered in seven. Fixation was secured by plates and screws, percutaneous
      Steinmann pins, or intramedullary Steinmann pins. There were no delayed unions or
      nonunions, no infections, and no neurovascular injuries. The average follow-up
      was 12.3 months; all 17 fractures had excellent results (forearm rotation loss of
      < 10 degrees). Our study indicates that excellent results can be expected with no
      increased risk of complications if the treating physician elects to proceed with
      an ORIF in a pediatric forearm fracture with proper indications.

PMID- 8865054
TI  - Single-bone fixation of both-bone forearm fractures.
AB  - Seventeen children with diaphyseal both-bone forearm fractures, for which closed
      reduction had failed, were treated with fixation of either the radius or ulna.
      Sixteen were followed up to their clinical end point. Results in all children
      were excellent; all had a full return of motion except two who lacked 5 degrees
      of pronation. This retrospective series is the first reported to date looking
      exclusively at diaphyseal both-bone forearm fractures in children treated with
      fixation of a single bone. The rationale of treatment is to stabilize one bone
      while the other is rotated into reduction. Repeated anesthetics are avoided, and
      malreduction is prevented without adult-style both-bone plating. We prefer
      intramedullary fixation as hardware is easier and safer to place and remove.

PMID- 8865055
TI  - Randomized double-blind trial of low- and moderate-dose lidocaine regional
      anesthesia for forearm fractures in childhood.
AB  - We undertook a randomized double-blind trial to compare the efficacy of 1.5 mg/kg
      body weight (low dose) and 3 mg/kg (moderate dose) lidocaine regional anesthesia
      for closed reductions of forearm fractures in childhood. Of the 283 children
      studied, 143 were randomized to the moderate-dose group and 140 to the low-dose
      group. The characteristics of the children and their injuries did not differ
      significantly. There were no complications due to lidocaine toxicity. In children
      with angulated and incompletely displaced fractures, satisfactory anesthesia was
      achieved in 94% of those receiving the low dose and in 97% of those receiving the
      moderate dose of lidocaine. In children with completely displaced fractures,
      satisfactory anesthesia was achieved in 93% of those receiving the moderate dose
      but in only 67% of those receiving the low dose of lidocaine. We conclude that
      the low-dose lidocaine protocol is suitable for children requiring closed
      reductions of angulated and incompletely displaced fractures of the forearm. In
      contrast, the moderate-dose lidocaine protocol is more reliable in children with
      displaced forearm fractures. Meticulous adherence to the protocols is essential
      to prevent systemic lidocaine toxicity from premature deflation of the
      tourniquet. This potential risk is further reduced by use of the low-dose
      protocol, which is applicable to approximately 70% of the children with forearm
      fractures requiring closed reductions.

PMID- 8865056
TI  - Epiphyseal distraction and centrally located bone bar: an experimental study in
      the rabbit.
AB  - The purpose of this study was to analyze the force required for an epiphysiolysis
      in vitro in the distal femoral growth plate of rabbits with different sized
      central physeal bone bars. The bars were operatively induced by drilling through
      the physis. An epiphyseal distraction was then performed, and the response was
      evaluated. Forty rabbits (67 femurs) divided into five groups were used for
      experimentation. Group A had not been operated on and manifested no physeal bone
      bridge. Groups B, C, D, and E manifested some bone bridges obtained surgically by
      drills 2, 2.5, 3.5, and 4.5 mm in diameter, respectively. The average force
      required to obtain an epiphysiolysis is not statistically significant in the
      different groups. However, we noted that the epiphysiolysis differed depending on
      the diameter of the surgically performed bridge. Group E was Salter-Harris type
      II fractures, whereas groups A, B, and C were type I fractures. Group D comprised
      both types.

PMID- 8865057
TI  - Lower extremity lawn-mower injuries in children.
AB  - Lower extremity lawn-mower injuries in children result in significant morbidity
      with a significant financial burden to the family and society. We reviewed 24
      children with lower extremity lawn-mower injuries; all mothers completed
      standardized psychologic assessments of their children, and 18 children were
      interviewed. Fifty percent of the mothers had defensive profiles on the
      standardized psychologic assessment, suggesting the likelihood of denial or
      underreporting of the child's psychologic difficulties. Therefore, we found the
      interview with the child to be a more accurate measure of psychologic distress.
      Prevention measures aimed at parents must emphasize that a child must not be
      allowed in a yard that is being mowed with a riding mower.

PMID- 8865058
TI  - Anterior cruciate ligament injuries in skeletally immature patients.
AB  - Twenty-eight consecutive, skeletally immature patients (9.9-15.0 years of age at
      the time of injury) with total rupture of the anterior cruciate ligament (ACL)
      were followed up for 3-5 years. The aims of the study were to monitor the natural
      course of conservative treatment, to identify variables relevant to failure of
      conservative treatment, and to evaluate an over-the-top procedure for ACL
      reconstruction by using the semitendinosus tendon and avoiding the physes. The
      patients were interviewed according to Lysholm knee score and Tegner activity
      level. Knee laxity and muscle torque were measured. Five patients insisted on
      immediate reconstruction. Twenty-three patients were sent to a 3-month
      rehabilitation program. Sixty-eight percent of the patients, who made an attempt
      with conservative treatment, had been operated on at follow-up. The patients not
      operated on were younger at injury and had a lower activity level at follow-up.
      The surgical procedure improved objective and subjective knee function, but there
      was a correlation between high activity level and a low Lysholm score.

PMID- 8865059
TI  - Traumatic and iatrogenic neurological complications after supracondylar humerous
      fractures in children.

PMID- 8865060
TI  - Extra-articular triplane fracture of the distal tibial epiphysis.

PMID- 8865061
TI  - Monitoring calcium in turtle hair cells with a calcium-activated potassium
      channel.
AB  - 1. An apamin-sensitive Ca(2+)-activated K+ channel was characterized in turtle
      hair cells and utilized to monitor submembranous intracellular Ca2+ and to
      evaluate the concentration of the mobile endogenous calcium buffer. 2. Isolated
      hair cells were voltage clamped with whole-cell patch electrodes filled with a
      Cs(+)-based intracellular solution to block the large-conductance Ca(2+)
      activated K+ (BK) channel. Ca2+ currents evoked by depolarization were followed
      by inward tail currents lasting several hundred milliseconds. Both the Ca2+
      current and slow tail current were abolished by nifedipine. 3. The tail current
      was carried by K+ and Cs+ (relative permeabilities PCa/PK = 0.22), and was fully
      blocked by 0.1 microM apamin and half blocked by 5 mM external TEA. These
      properties suggest the tail current flows through a Ca(2+)-activated K+ channel
      distinct from the BK channels. 4. Intracellular Ca2+ was imaged with a confocal
      microscope in hair cells filled with the indicator Calcium Green-5N introduced
      via the patch pipette. Increases in Ca2+ evoked by depolarization were localized
      to hotspots on the basolateral surface of the cell. The time course of the tail
      current closely matched the fast component of the fluorescenece monitored at a
      hotspot. 5. Ca(2+)-ATPase pump inhibitors thapsigargin, 2,4-di-(t
      butyl)hydroquinone (BHQ) and vanadate, which are known to influence calcium
      regulation in turtle hair cells, prolonged the time course of the tail current,
      supporting the idea that the channel monitors cytoplasmic Ca2+. 6. The mobile
      endogenous buffer was estimated by combining perforated-patch and whole-cell
      recordings on a single cell. After recording tail currents with an amphotericin
      perforated patch, the patch was ruptured to obtain the whole-cell mode, thus
      allowing washout of soluble cytoplasmic proteins and exchange with pipette
      buffers. By varying the concentration of Ca2+ buffer in the pipette, the mobile
      endogenous buffer was found to be equivalent to about 1 mM BAPTA.

PMID- 8865062
TI  - Ca2+ influx and activation of a cation current are coupled to intracellular Ca2+
      release in peptidergic neurons of Aplysia californica.
AB  - 1. Stimulation of inputs to bag cell neurons in the abdominal ganglion of Aplysia
      californica causes an increase in their intracellular Ca2+ concentration
      ([Ca2+]i). We have used thapsigargin, a specific inhibitor of the endoplasmic
      reticulum Ca2+ pump, to analyse the effects of Ca2+ released from intracellular
      stores on the electrophysiological responses of bag cell neurons. 2. Using
      digital imaging of fura-2-loaded isolated bag cell neurons we found that
      thapsigargin rapidly evoked an increase in [Ca2+]i in somata, with smaller
      increases in neurites. Thapsigargin-induced elevation of [Ca2+]i peaked at about
      1 microM within 5-10 min and then decayed to basal levels by 30 min. 3. Placement
      of an extracellular vibrating Ca(2+)-selective microelectrode to within 1 micron
      of somata revealed a relatively large steady-state Ca2+ efflux. Thapsigargin
      produced a rapid increase in Ca2+ influx. Changes in Ca2+ flux were not detected
      at neurites. 4. Thapsigargin produced a small depolarization in isolated bag cell
      neurons in artificial sea water (ASW). Sometimes enhanced depolarizations were
      observed when extracellular Na+ was replaced by TEA or Tris, but not N-methyl-D
      glucamine (NMDG). The depolarization was not blocked by 100 microM tetrodotoxin
      (TTX), removal of extracellular Ca2+ (0.5 mM EGTA) or addition of 10 mM Co2+ to
      the bath solution. 5. In voltage-clamp experiments, thapsigargin induced an
      inward current (ITg) that was recorded in Ca(2+)-free media containing TEA or
      Tris substituted for Na+. The apparent reversal potential of ITg was -16.8 +/-
      1.2 mV in TEA-ASW. Induction of ITg was inhibited in neurons that were
      microinjected with the Ca2+ chelator BAPTA-Dextran70 or treated with the membrane
      permeant analogue BAPTA AM. Activation of ITg was not observed when Na+ was
      replaced with NMDG. Manipulation of [Na+]o and [K+]o produced shifts in the
      reversal potential of ITg consistent with the underlying channels being permeable
      to both Na+ and K+. 6. Thapsigargin did not alter the amplitude or kinetics of
      voltage-activated Ba2+ currents, but in some experiments it did increase the
      amplitude of a component of outward K+ current. 7. Thapsigargin neither induced
      bag cell neurons within the intact ganglion to depolarize and fire spontaneously,
      nor did it alter the frequency or duration of firing of an electrically
      stimulated bag cell after-discharge. 8. We conclude that thapsigargin-sensitive
      Ca2+ pools are present predominantly in the somata of bag cell neurons. Ca2+ that
      is released from thapsigargin-sensitive Ca2+ stores activates a non-selective
      cation current that may help sustain depolarization of the somata, but does not
      by itself trigger an after-discharge.

PMID- 8865063
TI  - Calcium gradients during excitation-contraction coupling in cat atrial myocytes.
AB  - 1. Confocal microscopy in combination with the calcium-sensitive fluorescent
      probe fluo-3 was used to study spatial aspects of intracellular Ca2+ signals
      during excitation-contraction coupling in isolated atrial myocytes from cat
      heart. 2. Imaging of [Ca2+]i transients evoked by electrical stimulation revealed
      that Ca2+ release started at the periphery and subsequently spread towards the
      centre of the myocyte. 3. Blocking sarcoplasmic reticulum (SR) Ca2+ release with
      50 microM ryanodine unmasked spatial inhomogeneities in the [Ca2+]i was higher in
      the periphery than in central regions of the myocyte. 4. Positive (or negative)
      staircase or postrest potentiation of the 'whole-cell' [Ca2+] transients were
      paralleled by characteristic changes in the spatial profile of the [Ca2+]i
      signal. With low SR Ca2+ load [Ca2+]i transients in the subsarcolemmal space were
      small and no Ca2+ release in the centre of the cell was observed. Loading of the
      SR increased subsarcolemmal [Ca2+]i transient amplitude and subsequently
      triggered further release in more central regions of the cell. 5. Spontaneous
      Ca2+ release from functional SR units, i.e. Ca2+ sparks, occurred at higher
      frequency in the subsarcolemmal space than in more central regions of the
      myocyte. 6. Visualization of the surface membrane using the membrane-selective
      dye Di-8-ANEPPS demonstrated that transverse tubules (t-tubules) were absent in
      atrial cells. 7. It is concluded that in atrial myocytes voltage-dependent Ca2+
      entry triggers Ca2+ release from peripheral coupling SR that subsequently induces
      further Ca2+ release from stores in more central regions of the myocyte.
      Spreading of Ca2+ release from the cell periphery to the centre accounts for
      [Ca2+]i gradients underlying the whole-cell [Ca2+]i transient. The finding that
      cat atrial myocytes lack t-tubules demonstrates the functional importance of Ca2+
      release from extended junctional (corbular) SR in these cells.

PMID- 8865064
TI  - Effect on the indo-1 transient of applying Ca2+ channel blocker for a single beat
      in voltage-clamped guinea-pig cardiac myocytes.
AB  - 1. We used rapid solution changes to investigate the mechanisms which trigger
      Ca2+ release from the sarcoplasmic reticulum (SR) in guinea-pig ventricular
      myocytes. We patch-clamped myocytes at 36 degrees C and used indo-1 to monitor
      intracellular Ca2+. Before each test pulse, we established a standard level of SR
      Ca2+ load by applying a train of conditioning pulses. 2. We switched rapidly to
      32 microM nifedipine (an L-type Ca2+ current (ICa,L) blocker) 8 s before a test
      pulse, and just after applying nifedipine we applied a ramp depolarization to pre
      block Ca2+ channels. We found that ICa,L elicited by the following test pulse was
      inhibited almost completely (98-99% inhibition). 3. The indo-1 transient elicited
      by an 800 ms depolarizing pulse showed a rapid initial rise which was inhibited
      by ryanodine-thapsigargin. This indicated that the rapid rise was due to Ca2+
      release from the SR, and therefore provides an index of SR Ca2+ release. 4. In
      cells dialysed internally with 10 mM Na(+)-containing solution, nifedipine
      application before a +10 mV test pulse blocked 62% of the rapid initial phase of
      the indo-1 transient. Calibration curves of indo-1 for intracellular Ca2+ (using
      a KD of indo-1 for Ca2+ of either 250 or 850 nM, the reported range) indicated
      that between 67 and 76% of the Ca2+i transient was inhibited by nifedipine. Thus,
      in cells dialysed with 10 mM Na+ and depolarized to +10 mV, and in the absence of
      ICa,L, this suggests that another trigger mechanism for SR release is able to
      trigger between 33 and 24% of the Ca2+i transient. 5. For a given dialysing Na+
      concentration, the fraction of indo-1 transient which was inhibited by nifedipine
      decreased as test potential became more positive. In cells dialysed with 10 mM
      Na+ and pulsed to +110 mV, 24% of the rapid phase of the indo-1 transient was
      inhibited by nifedipine (equivalent to between 27 and 37% of the Ca2+i
      transient). 6. For a given test potential, the fraction of the indo-1 transient
      which was inhibited by nifedipine decreased as dialysing Na+ concentration
      increased. In cells dialysed with Na(+)-free solution and pulsed to +10 mV, 84%
      of the indo-1 transient was inhibited by nifedipine (equivalent to between 88 and
      91% of the Ca2+i transient). In contrast, in cells dialysed with 20 mM Na+ and
      pulsed to +10 mV, 41% of the indo-1 transient was inhibited by nifedipine
      (equivalent to between 47 and 57% of the Ca2+i transient). 7. Dialysing cells
      with different Na+ concentrations could lead to a different SR Ca2+ content. We
      therefore manipulated the conditioning train before each test pulse to change the
      extent of SR loading. For each dialysing Na+ concentration, we found no change in
      the degree to which nifedipine blocked the indo-1 transient when SR content was
      either increased or decreased. 8. The results support the idea that both ICa, L
      and a second mechanism are able to trigger SR release and the resulting Ca2+i
      transient. When ICa, L was blocked with nifedipine, the fraction of Ca2+i
      transient which remained increased with more positive test potential and higher
      internal Na+. This is consistent with the hypothesis that the second SR trigger
      mechanism is Ca2+ entry via reverse Na(+)-Ca2+ exchange, elicited by a step
      change in membrane potential.

PMID- 8865065
TI  - Cyclic GMP-gated channels of bovine rod photoreceptors: affinity, density and
      stoichiometry of Ca(2+)-calmodulin binding sites.
AB  - 1. Ca(2+)-loaded vesicles of bovine rod outer segment (ROS) membranes were used
      to examine the influence of Ca(2+)-calmodulin (Ca(2+)-CaM) on the activity of
      cGMP-gated channels. 2. In vesicles prepared from ROS membranes which were washed
      at zero free Ca2+, Ca(2+)-CaM reduced the Ca2+ flux to maximally 40%. The dose
      response curve for activation of the cGMP-gated channel had a half-maximal value
      of 36.8 +/- 2 microM in the CaM-free state, and of 55.6 +/- 5.2 microM in the
      Ca(2+)-CaM-bound state. In both cases the Hill coefficients were 2.2 +/- 0.2. 3.
      In vesicles prepared from ROS membranes which were washed at 100 microM Ca2+, the
      dose-response curve was identical to the Ca(2+)-CaM-bound state. 4. Titration of
      the Ca(2+)-CaM-dependent decrease of the channel activity upon addition of 40
      microM cGMP yielded half-maximal Ca(2+)-CaM concentrations (EC50CaM) which were
      linearly correlated with the concentration of membrane vesicles. Extrapolation of
      EC50CaM to infinite dilution of vesicles yielded a Ca(2+)-CaM affinity constant
      for the cGMP-gated channel of 1.01 +/- 0.20 nM. Hill analysis of the Ca(2+)-CaM
      titrations resulted in a Hill coefficient of 1.36 +/- 0.15. 5. From the slope of
      the linear regression of EC50CaM plotted vs. the rhodopsin concentration, the
      molar ratio of rhodopsin to externally accessible Ca(2+)-CaM binding sites of
      fused ROS membranes was determined to be 1439 +/- 109. Therefore, there are about
      720 molecules of rhodopsin per Ca(2+)-CaM binding site present in ROS. 6. Based
      on these data, a density of 560 Ca(2+)-CaM binding sites micron-2 is estimated
      for the plasma membrane of bovine ROS, suggesting that there are two Ca(2+)-CaM
      binding sites per channel. 7. The Ca(2+)-CaM effect did not become noticeable
      until the ROS membranes were hypotonically washed at free [Ca2+] below 100 nM,
      suggesting that an endogenous Ca(2+)-binding protein was washed off in the
      absence of Ca2+. 8. If the endogenous Ca(2+)-binding protein of bovine ROS
      membranes was washed off at zero Ca2+ and then Ca(2+)-CaM added, Ca(2+)-CaM could
      only be washed off again at free [Ca2+] below 100 nM. 9. These findings strongly
      suggest that the endogenous Ca(2+)-binding protein of the bovine cGMP-gated
      channel is CaM.

PMID- 8865066
TI  - The mechanism of calcium channel facilitation in bovine chromaffin cells.
AB  - 1. This study was planned to clarify the mechanism of Ca2+ channel facilitation
      by depolarizing prepulses given to voltage-clamped bovine chromaffin cells. The
      hypothesis for an autocrine modulation of such channels was tested by studying
      the effects of a soluble vesicle lysate (SVL) on whole-cell Ba2+ currents (IBa).
      2. SVL was prepared from a bovine adrenal medullary homogenate. The ATP content
      in this concentrated SVL amounted to 3.18 +/- 0.12 mM (n = 4). The concentration
      of noradrenaline and adrenaline present in the SVL was 11.2 +/- 0.97 and 15.2 +/-
      2 mM, respectively (n = 5). A 1:1000 dilution of SVL in the external solution
      halved the magnitude of IBa and produced a 7-fold slowing of its activation
      kinetics. The blocking effects of SVL were concentration dependent and quickly
      reversed upon washout. 3. Inhibition and slowing of the kinetics of IBa by SVL
      could be partially reversed by strong depolarizing prepulses (+90 mV, 45 ms).
      This reversal of inhibition, called Ca2+ channel facilitation, persisted in the
      presence of 3 microM nifedipine. 4. Intracellular dialysis of GDP-beta-S (0.5 mM)
      or pretreatment of the cells with pertussis toxin (100 ng ml-1 for 18-24 h)
      prevented the reduction in peak current caused by a 1:100 dilution of SVL; no
      prepulse facilitation could be observed under these conditions. 5. The receptor
      blockers naloxone (10 microM) or suramin (100 microM) and PPADS (100 microM)
      largely antagonized the effects of SVL. Treatment of SVL with alkaline
      phosphatase or dialysis against a saline buffer to remove low molecular mass
      materials (< 10 kDa) considerably reduced the activity of SVL. 6. Stopping the
      flow of the external solution (10 mM Ba2+) gradually reduced the size, and slowed
      down the activation phase, of the current. Prepulse facilitation of IBa was
      absent or weak in a superfused cell, but was massive upon flow-stop conditions in
      the presence or absence of 3 microM nifedipine. 7. Our experiments suggest that
      facilitation by prepulses of whole-cell current through Ca2+ channels is due to
      the suppression of an autoinhibitory autocrine loop present in bovine chromaffin
      cells. By acting at least on purinergic and opiate receptors, the exocytotic
      release of ATP and opiates will cause a tonic inhibition of the current through a
      G-protein-mediated mechanism. Such a mechanism will be removed by strong
      depolarizing prepulses, and will involve preferentially non-L-type channels. In
      the light of these and other recent results, previously held views on the
      selective recruitment by prepulses of dihydropyridine-sensitive Ca2+ channels are
      not tenable.

PMID- 8865067
TI  - The effects of beta-stimulation on the Na(+)-K+ pump current-voltage relationship
      in guinea-pig ventricular myocytes.
AB  - 1. The whole cell patch clamp technique was used to study effects of the beta
      agonist isoprenaline (Iso) on the current-voltage (I-V) relationship of the Na(+)
      K+ pump current (Ip) in acutely isolated guinea-pig ventricular myocytes. 2. The
      effect of Iso on Ip at high [Ca2+]i (1.4 microM) was voltage dependent. The I-V
      relationship of Ip in Iso shifted by approximately 30 mV in the negative
      direction on the voltage axis, increasing Ip at negative voltages but leaving Ip
      unchanged at positive voltages. 3. Intracellular application of the calmodulin
      antagonist, calmodulin-dependent protein kinase II fragment 290-309, did not
      eliminate or reduce the Iso-induced voltage shift, suggesting calmodulin
      dependent protein kinase II was not involved. 4. The Iso inhibition of Ip at low
      [Ca2+]i (15 nM) was not voltage dependent. Ip was reduced by 20 to 30% in the
      presence of Iso at each holding potential. 5. When the voltage dependence of Ip
      was largely reduced by substitution of N-methyl-D-glucamine+ for external Na+,
      the magnitude of the low [Ca2+]i, Iso-induced inhibition of Ip was progressively
      eliminated by increasing the [Ca2+]i. At a [Ca2+]i of 1.4 microM, this inhibition
      disappeared. 6. At intermediate values of [Ca2+]i, the I-V curves in Na(+)
      containing solution in the presence and the absence of Iso crossed over. The
      higher the [Ca2+]i, the more positive the voltage at which the two I-V curves
      intersected. 7. During beta-adrenergic activation our results suggest
      intracellular Ca2+ has two effects: (a) It prevents protein kinase A (PKA)
      phosphorylation-induced inhibition of Ip. (b) It causes a PKA phosphorylation
      induced shift of the pump I-V relationship in the negative direction on the
      voltage axis. These effects may have important physiological significance in the
      regulation of heart rate and cardiac contractility.

PMID- 8865068
TI  - The sulphonylurea receptor confers diazoxide sensitivity on the inwardly
      rectifying K+ channel Kir6.1 expressed in human embryonic kidney cells.
AB  - 1. We have examined the effects of diazoxide and intracellular ATP (ATPi) on
      whole-cell currents in HEK293 cells transfected transiently with the inwardly
      rectifying K+ channel Kir6.1 (uKATP1) or cotransfected with Kir6.1 and the
      sulphonylurea receptor (SUR1). 2. Kir6.1 currents were unaffected by the K+
      channel opener diazoxide or by dialysis with 0.3 mM ATPi. 3. Kir6.1-SUR1 currents
      increased in amplitude when cells were dialysed with 0.3 mM ATP, but not with 5
      mM ATP. This activation may be explained by the loss of endogenous ATP from the
      cell when the intracellular solution contains 0.3 mM ATP. Kir6.1-SUR1 currents
      were also activated by diazoxide; this activation was greater with 0.3 mM ATP1
      than with 5 mM ATP1. 4. We conclude that SUR1 is required to confer both
      diazoxide and ATP sensitivity on Kir6.1.

PMID- 8865069
TI  - The properties and distribution of inward rectifier potassium currents in pig
      coronary arterial smooth muscle.
AB  - 1. Whole-cell potassium currents were studied in single smooth muscle cells
      enzymatically isolated from pig coronary arteries. 2. In cells isolated from
      small diameter branches of the left anterior descending coronary artery (LAD), an
      inward rectifier potassium current (IK(IR)) was identified, which was inhibited
      by extracellular barium ions, suggesting the presence of inward rectifier
      potassium (KIR) channels. 3. The conductance for IK(IR) measured in 6, 12, 60 and
      140 mM extracellular potassium was a function of membrane potential and the
      extracellular potassium concentration. 4. On hyperpolarization, IK(IR) activated
      along an exponential time course with a time constant that was voltage dependent.
      5. Inward rectifier current was compared in cells isolated from coronary vessels
      taken from different points along the vascular tree. Current density was greater
      in cells isolated from small diameter coronary arteries; at -140 mV it was -20.5
      +/- 4.4 pA pF-1 (n = 23) in 4th order branches of the LAD, but -0.8 +/- 0.2 pA pF
      1 (n = 11) in the LAD itself. 6. In contrast to IK(IR), there was little effect
      of arterial diameter on the density of voltage-dependent potassium current;
      densities at +30 mV were 12.8 +/- 1.3 pA pF-1 (n = 19) in 4th order branches and
      17.4 +/- 3.1 pA pF-1 (n = 11) in the LAD. 7. We conclude that KIR channels are
      present in pig coronary arteries, and that they are expressed at a higher density
      in small diameter arteries. The presence of an enhanced IK(IR) may have
      functional consequences for the regulation of cell membrane potential and tone in
      small coronary arteries.

PMID- 8865070
TI  - Voltage- and time-dependent block of delayed rectifier K+ current in rabbit sino
      atrial node cells by external Ca2+ and Mg2+.
AB  - 1. The properties of the delayed rectifier K+ current (IK) of rabbit isolated
      sino-atrial node cells were investigated in high (140 mM) [K+]o using the whole
      cell-clamp technique. 2. Hyperpolarizing clamp pulses from 0 mV induced an
      instantaneous current jump (I-V relation linear) followed by a time-dependent
      increase in inward current to a peak, whereas depolarizing clamp pulses induced
      little outward current. The peak I-V relation showed a strong inward
      rectification. The inwardly rectifying current was blocked by E-4031. 3. The
      inward K+ current induced by hyperpolarizing clamp pulses from 0 mV relaxed after
      reaching its peak. The rate of the relaxation increased as the membrane potential
      became more negative and concentrations of external Ca2+ or Mg2+ were increased.
      The steady-state current was smaller as the relaxation of the current accelerated
      on increasing [Ca2+]o or [Mg2+]o. 4. Depolarizing clamp pulses from -80 mV
      induced an increase in inward current, reaching a steady state. The amplitude of
      the steady-state current became smaller and the rate of current increase became
      slower as [Ca2+]o or [Mg2+]o was increased. 5. The effects of Ca2+ and Mg2+ are
      well explained by a time- and voltage-dependent blockade of the K+ channel by
      these ions. The fractional electrical distance of the binding site calculated
      from the voltage dependence of the blocking rate constant is 0.69 for Ca2+ and
      0.88 for Mg2+. The blocking rate constant at 0 mV for Ca2+ is about 15 times
      faster than that for Mg2+, indicating stronger effects of Ca2+. 6. A re
      interpretation of IK in sino-atrial node cells is proposed: there are two
      independent gates (an activation gate which opens on hyperpolarization and an
      inactivation gate which closes on hyperpolarization) and a binding site for Ca2+
      and Mg2+ inside the channel. Binding of these ions, which is facilitated by
      hyperpolarization, causes channel blockade, resulting in the observed voltage
      dependence of IK in physiological concentrations of Ca2+ and Mg2+.

PMID- 8865071
TI  - Novel glial-neuronal signalling by coactivation of metabotropic glutamate and
      beta-adrenergic receptors in rat hippocampus.
AB  - 1. We have previously reported that activation of group II-like metabotropic
      glutamate receptors (mGluRs) in rat hippocampus results in a potentiation of the
      accumulation of cAMP elicited by activation of G-protein Gs-coupled receptors.
      This large increase in cAMP levels results in release of cAMP or a cAMP
      metabolite and depression of synaptic transmission at the Schaffer collateral-CA1
      pyramidal cell synapse through activation of A1 adenosine receptors. 2.
      Consistent with these studies, we report that antagonists of group II mGluRs
      block both the potentiation of cAMP accumulation elicited by activation of mGluRs
      and the depression of synaptic transmission induced by coactivation of mGluRs and
      beta-adrenergic receptors. 3. In situ hybridization studies suggest that of the
      cloned group II mGluRs only mGluR-3 mRNA is present in area CA1. Interestingly,
      mGluR-3 appears to be present predominantly in glia in this region. Thus, we
      tested the hypothesis that mGluRs coupled to potentiation of cAMP accumulation
      were present on glia rather than neurons in area CA1. 4. The selective group II
      mGluR agonist 2S,1'R,2'R,3'R-2(2,3-dicarboxycyclo-propyl)glycine (DCG-IV) failed
      to enhance cAMP-mediated electrophysiological responses to the beta-adrenergic
      receptor agonist isoprenaline (Iso) in CA1 pyramidal cells, suggesting that
      mGluRs coupled to potentiation of cAMP accumulation may not be present in these
      cells. 5. Pre-incubation of hippocampal slices with either of the selective glial
      toxins L-alpha-aminoadipic acid (L-AA) or fluorocitrate (FC) blocked mGluR
      mediated potentiation of cAMP accumulation. However, L-AA and FC had no
      discernible effects on viability of CA1 pyramidal cells, or cAMP-mediated
      electrophysiological effects in these neurons. 6. Pre-incubation of hippocampal
      slices with the neurotoxin kainate resulted in disruption of neuronal
      transmission and degeneration of neurons in area CA1, but had no effect on mGluR
      mediated potentiation of cAMP accumulation. 7. Pre-incubation of hippocampal
      slices with the cAMP/cAMP metabolite transport blocker probenicid blocked the
      depression of synaptic transmission elicited by coapplication of Iso and DCG-IV,
      while having no significant effect on cAMP accumulation elicited by these
      agonists. 8. Taken together, these data suggest that mGluRs coupled to
      potentiation of cAMP accumulation are present on glia rather than neurons in area
      CA1 of hippocampus. This suggests that a novel form of glial-neuronal
      communication may exist, since activation of these mGluRs in concert with beta
      adrenergic receptors results in depression of synaptic transmission.

PMID- 8865072
TI  - Mechanisms underlying orientation selectivity of neurons in the primary visual
      cortex of the macaque.
AB  - 1. Effects of blocking intracortical inhibition by microiontophoretic
      administration of bicuculline methiodide (BMI), a selective antagonist for GABAA
      receptors, on orientation selectivity of 109 neurones were studied in the primary
      visual cortex (V1) of anaesthetized and paralysed monkeys. 2. The averaged
      orientation tuning of visual responses of cells was poor in cytochrome
      oxidaserich blobs of layer II/III and in layer IVc beta, moderate in layers IVb,
      IVc alpha and V, and sharp in the interblob region of layer II/III and in layers
      IVa and VI. 3. Iontophoretic administration of BMI reduced the sharpness of
      orientation tuning of cells to a varying extent in each layer. In most cells,
      furthermore, the originally ineffective stimuli induced visual responses during
      the BMI administration, suggesting that excitatory inputs evoked by the non
      optimally oriented stimuli were masked by GABAergic inhibition. Nevertheless, the
      maximal facilitation was observed in the response to the optimally or near
      optimally oriented stimuli. 4. There was a difference in such an effect of BMI
      among layers. Orientation selectivity of cells in interblobs in layer II/III and
      in layer IVb was sensitive to BMI whereas that of cells in layer VI was
      relatively insensitive to BMI, suggesting a larger contribution of excitatory
      mechanisms to the orientation selectivity in this layer. 5. In the orientation
      selective cells, an analysis of the magnitude of excitation and inhibition evoked
      by stimuli at various orientations suggests that both inputs tune around the
      optimal orientation and their magnitudes are almost proportional to each other
      except at the optimal orientation. This analysis also indicates that the
      orientation tuning of inhibition had a less prominent peak around the optimal
      orientation than that of excitation. This dominance of excitation over inhibition
      around the optimal orientation may function to accentuate the response to the
      optimally oriented stimulus. 6. These results suggest that, in the monkey V1, the
      orientation selectivity of cells is largely dependent on the orientation-biased
      excitatory and inhibitory inputs which have a broader tuning profile, covering
      from the optimal to null-orientation, than that observed in extracellularly
      recorded responses at the control level.

PMID- 8865073
TI  - Pancreatic secretion evoked by cholecystokinin and non-cholecystokinin-dependent
      duodenal stimuli via vagal afferent fibres in the rat.
AB  - 1. We have recently demonstrated that cholecystokinin (CCK) at physiological
      levels stimulates pancreatic enzyme secretion via gastroduodenal mucosal vagal
      afferent fibres in the rat. The present study was designed to investigate if non
      CCK-mediated pancreatic stimuli which activate duodenal receptors also utilize
      similar vagal afferent pathways. 2. Intraduodenal administration of maltose (300
      mM), hypertonic saline (500 mosmol l-1) and mucosal light stroking in
      anaesthetized rats evoked 70, 57 and 200% increases, respectively, in pancreatic
      protein secretion with no changes in plasma CCK concentration. Administration of
      the CCK receptor antagonist L364,718 did not affect pancreatic secretion evoked
      by these luminal stimuli. 3. Administration of atropine, acute vagotomy and
      duodenal mucosal application of capsaicin each completely abolished the
      pancreatic response to these stimuli. 4. Infusion of a subthreshold dose of the
      octapeptide of CCK (15 pmol (kg body wt)-1 h-1) potentiated the pancreatic
      response to duodenal infusion of maltose (300 mM) and hypertonic saline (500
      mosmol l-1). 5. In conscious rats, perivagal application of capsaicin abolished
      the pancreatic response evoked by physiological doses of CCK and intraduodenal
      administration of maltose or hypertonic saline, confirming the physiological
      relevance of the observations in anaesthetized rats. 6. These results suggest
      that like CCK, non-CCK-mediated luminal stimuli evoke pancreatic enzyme secretion
      via stimulation of a vagal afferent pathway originating from the duodenal mucosa.

PMID- 8865074
TI  - Non-ionic diffusion and carrier-mediated transport drive extracellullar pH
      regulation of mouse colonic crypts.
AB  - 1. Extracellular pH (pHo) regulation within mouse colonic crypt lumens is
      stimulated by transepithelial gradients of short-chain fatty acids (SCFAs).
      Current work assesses underlying mechanisms contributing to pHo regulation. 2.
      Crypt luminal alkalinization was saturable by apical SCFA (substrate
      concentration activating half-maximal transport (KT) of isobutyrate = 45 mM).
      However, saturation was consistent with either carrier-mediated SCFA flux or non
      ionic diffusion, because the non-ionized form was titrated by luminal
      alkalinization. Direct acidification of apical perfusates increased the magnitude
      of SCFA-induced luminal alkalinization, roughly in the same proportion to the
      increased concentration of non-ionized SCFA in the crypt lumen. 3.
      Transepithelial gradients of an alternative weak acid (CO2) produce pHo changes
      similar to SCFA. In contrast, a weak base (NH3) changes pHo with reverse
      dependence on the orientation of the transepithelial gradient compared with SCFA.
      Results implicate non-ionic diffusion in pHo regulation, and suggest that pHo
      changes may underly SCFA-stimulated bicarbonate secretion and ammonium
      absorption. 4. SCFA metabolism plays a minor role in extracellular pH regulation.
      An avidly metabolized SCFA (N-butyrate) augments crypt luminal alkalinization
      only slightly (0.08 pH units) versus a poorly metabolized SCFA (isobutyrate). 5.
      Apical addition of 1 mM 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid
      (DIDS) partially inhibits luminal alkalinization caused by apical SCFA. DIDS has
      no effect on luminal alkalinization caused by transepithelial CO2 gradients.
      Probenecid (1 mM), alpha-cyano-4-hydroxycinnamic acid (4 mM) or basolateral DIDS
      (1 mM) do not affect pHo regulation. Results suggest that DIDS-sensitive, SCFA
      dependent transport in the colonocyte apical membrane contributes to pHo
      regulation.

PMID- 8865075
TI  - A model for the kinetics of neutral and anionic dipeptide-proton cotransport by
      the apical membrane of rat kidney cortex.
AB  - 1. Kinetics of influx (mediated through peptide-proton cotransport) of two
      labelled dipeptides has been studied in apical membrane vesicles isolated from
      rat renal cortex. The substrates (neutral D-Phe-L-Ala and anionic D-Phe-L-Glu)
      have previously been shown to be transported through a single system but with
      different stoichiometry of proton coupling. 2. The initial rate of influx of both
      peptides was determined under a set of defined conditions allowing extravesicular
      pH, intravesicular pH, transmembrane pH and membrane potential (Em) to be varied
      systemically and independently. From this data the kinetic constants K(m) and
      Vmax were derived for each condition. Very substantial effects of pH, pH gradient
      and membrane potential were found; there were consistent quantitative differences
      when the substrates were compared. 3. Efflux of the two peptides from preloaded
      vesicles was also determined. At pH 5.5 (intra- and extravesicular), but not at
      pH 7.4, the rate constants for efflux of the two peptides were similar and
      addition to the extravesicular medium of unlabelled D-Phe-L-Glu (but not D-Phe-L
      Ala) trans-stimulated efflux of both peptides to a similar extent; the extent of
      this trans-stimulation was insensitive to alterations in membrane potential. 4. A
      model based on a combination of classical carrier theory (the carrier being
      negatively charged) and of two sequential protonation steps (both to external
      sites predicted to be in the membrane electrical field) is described.
      Qualitatively this adequately accounts for all the observations made and allows
      for the dependence of the stoichiometry of proton-peptide coupling on the net
      charge carried by the substrate. Quantitatively a 50-fold greater rate of
      reorientation of the free carrier when unprotonated is predicted to be
      responsible for the coupling of proton and peptide transport. 5. Our results and
      the model are discussed with respect to the recently elucidated primary structure
      of mammalian peptide transporters.

PMID- 8865076
TI  - Natriuretic effect of non-pressor doses of endothelin-1 in conscious dogs.
AB  - 1. Renal, endocrine and haemodynamic responses to separate intravenous infusions
      of three doses of endothelin-1 (40, 400 and 4000 fmol kg-1 min-1) were
      investigated in conscious dogs. 2. Administration of 40, 400 and 4000 fmol kg-1
      min-1 endothelin-1 for 120 min increased plasma endothelin-1 levels by two-,
      seven- and 250-fold, respectively. 3. The two low doses did not have measurable
      effects on mean arterial blood pressure and heart rate but tended to increase
      glomerular filtration rate. The high dose increased mean arterial blood pressure
      (MABP; from 104 +/- 4 to 138 +/- 4 mmHg, P < 0.05) and decreased heart rate (from
      71 +/- 4 to 46 +/- 3 beats min-1, P < 0.05) as well as glomerular filtration rate
      (from 47 +/- 3 to 19 +/- 5 ml min-1, P < 0.05). 4. At rates of 40 and 400 fmol kg
      1 min-1, endothelin-1 increased sodium excretion about five- and eightfold,
      respectively. Relative changes in fractional sodium excretion were very similar.
      The high dose was markedly antinatriuretic (reducing sodium excretion from 8.3 +/
      1.1 to 1.2 +/- 0.2 mumol min-1, P < 0.05). 5. Diuresis increased during the
      administration of the two lower doses, which did not change plasma atrial
      natriuretic peptide or vasopressin concentrations. Urine flow increased after
      termination of the infusion of the pressor dose despite elevated plasma
      vasopressin and subnormal glomerular filtration rate. 6. Infusion of endothelin-1
      at 40 fmol kg-1 min-1 did not change the concentrations of angiotensin II and
      atrial natriuretic peptide in plasma. Infusion of 400 fmol kg-1 min-1 was
      associated with a decrease in plasma angiotensin II, while plasma atrial
      natriuretic peptide was unchanged. The high dose of endothelin-1 markedly
      increased plasma levels of both hormones. 7. It is concluded that endothelin-1 at
      low plasma concentrations increases sodium excretion while a higher pressor dose
      of endothelin-1 is antinatriuretic. However, increases in plasma endothelin-1
      seem to elicit diuresis over a wide concentration range, although possibly by
      different mechanisms.

PMID- 8865077
TI  - Bicarbonate transport in sheep parotid secretory cells.
AB  - 1. Intracellular pH (pH1) was measured by microfluorimetry in secretory endpieces
      isolated from sheep parotid glands and loaded with the pH-sensitive fluoroprobe
      2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). 2. Stimulation with 1
      microM acetylcholine (ACh) caused a large, transient decrease in pH1 of 0.37 +/-
      0.02 pH units followed by a slower recovery. The transient, which was reduced by
      60% in the absence of HCO3-, could be attributed mainly to HCO3- efflux. During
      sustained stimulation, pH1 increased to a value that exceeded the resting value
      by 0.083 +/- 0.023 pH units after 20 min. 3. The anion channel blocker NPPB (0.1
      mM) reduced the transient acidification in response to ACh by 48% and raised pH1
      during sustained stimulation. Simultaneous application of NPPB and ACh
      accelerated the re-alkalinization following the initial acidification, indicating
      that NPPB inhibits HCO3- efflux. 4. The stilbene derivative H2DIDS (0.5 mM)
      reduced the transient acidification in response to ACh by 76% but caused a marked
      decrease in pH1 during sustained stimulation. Simultaneous application of H2DIDS
      and ACh slowed the re-alkalinization following the initial acidification,
      indicating that the main effect of H2DIDS was to inhibit HCO3- accumulation. 5.
      In the absence of HCO3-, the recovery from an acid load was unaffected by ACh
      stimulation. Acid extrusion, although dependent on Na+, was not inhibited by
      amiloride (1 mM), clonidine (1 mM) or H2DIDS (0.5 mM) and was therefore
      provisionally attributed to a Na(+)-H+ exchanger isoform other than NHE1 or NHE2.
      6. In the presence of HCO3-, the rate of recovery from an acid load was reduced
      during ACh stimulation, probably as a result of the increased efflux of HCO3-.
      Acid extrusion was dependent on Na+ and was significantly inhibited by H2DIDS. 7.
      We conclude that ACh-evoked HCO3- secretion in the sheep parotid gland differs
      from that in many other salivary glands by being driven predominantly by
      basolateral Na(+)-HCO3- cotransport rather than by Na(+)-H+ exchange.

PMID- 8865078
TI  - Calorigenic effect of diiodothyronines in the rat.
AB  - 1. In hypothyroid rats, we determined the effects of administration of different
      doses of 3,3',5-triiodo-L-thyronine (T3), 3,3'-diiodo-L-thyronine (3,3'-T2) and
      3,5-diiodo-L-thyronine (3,5-T2) ("T2 isomers' refers specifically to these latter
      two isomers throughout this paper) on resting metabolism (RM) and on the
      oxidative capacity (measured as cytochrome oxidase activity) of tissues that are
      metabolically very active. 2. The T2 isomers induced a dose-dependent calorigenic
      effect when injected I.P. into hypothyroid rats. The increase in RM was already
      evident at a dose of 2.5 micrograms (100 g body wt)(-1), and the greatest effect
      was observed at the highest dose, 10 micrograms (100 g body wt)(-1), when RM
      reached a value not significantly different from that of the euthyroid controls
      (1.92 +/- 0.08 and 1.93 +/- 0.13 (1 O2) kg(-1) h(-1) for 3,5'-T2, respectively,
      vs. 2.1 +/- 0.12 (1 O2) kg(-1) h(-1) for euthyroid controls). T3 administration
      restored RM to normal euthyroid values, even at a dose of 2.5 micrograms (100 g
      body wt)(-1). 3. The effect of T2 isomers on RM was paralleled by an increase in
      the oxidative capacity of tissues that are metabolically very active (liver,
      skeletal muscle, brown adipose tissue (BAT) and heart). The increases were
      between 33% (liver + 3,3'-T2) and 63% (muscle + 3,3'-T2). By contrast, T3 induced
      its greatest effect on the liver, with a smaller effect on skeletal muscle, but
      no significant stimulation in heart and BAT, whatever the dose. 4. These results
      suggest that T8 isomers might be mediators of the direct thyroid hormone
      regulation of energy metabolism.

PMID- 8865079
TI  - Growth and differentiation of fast and slow muscles in fetal sheep, and the
      effects of hypophysectomy.
AB  - 1. Isometric contractile characteristics of fast-twitch (flexor digitorum longus,
      FDL; medial gastrocnemius, MG) and slow-twitch (soleus) muscles were determined
      in pentobarbitone-anaesthetized fetal sheep between 90 and 140 days gestation.
      Five fetuses were hypophysectomized (HPX) at 90-95 days gestation and then
      studied at 138-140 days. 2. At 90-95 days gestation the time to peak of single
      twitch contractions for the soleus, MG and FDL were not significantly different
      from each other; the mean value (+/-S.E.M.) for all the muscles at this age was
      77.6 +/- 9.0 ms. At 120-125 days gestation the MG and FDL contracted
      significantly faster (44.0 +/- 0.9 and 40.8 +/- 1.8 ms, respectively) than at 90
      95 days, and did not change significantly thereafter. In contrast, the soleus
      muscle contracted more slowly (111.9 +/- 6.6 ms) at 138-140 days than at 90-95
      days and 120-125 days gestation. 3. Soleus muscle consisted of type I fibres at
      all gestational ages. There was no significant change with gestational age in the
      relative numbers of type I and II fibres in the MG and FDL, but in the diaphragm
      the number of type I fibres increased and the number of type II fibres decreased
      between 125 and 138 days gestation. 4. HPX abolished the normal increase of
      soleus weight relative to body weight between 125 and 138 days but did not alter
      the change of twitch contraction time with age. HPX significantly prolonged
      twitch time to peak and time to half-relaxation of MG and time to half-relaxation
      of FDL at 138 days. 5. The maximum rate of rise of the isometric tetanic
      contraction was unchanged by HPX in all three hindlimb muscles, but fatigue of MG
      and FDL was increased. 6. The relative proportions of different fibre types in
      the hindlimb muscles and the diaphragm were unchanged by HPX, but there was a
      significant decrease in mean areas of type I and II fibres in the FDL and MG of
      the HPX fetuses.

PMID- 8865080
TI  - Group I extensor afferents evoke disynaptic EPSPs in cat hindlimb extensor
      motorneurones during fictive locomotion.
AB  - 1. Intracellular recording from extensor motoneurones in paralysed decerebrate
      cats was used to examine the distribution of short-latency non-monosynaptic
      excitation by group I afferents during fictive locomotion produced by stimulation
      of the mesencephalic locomotor region (MLR). 2. During the extension but not the
      flexion phase of fictive locomotion, stimulation of ankle extensor nerves at 1.2
      2.0 times threshold evoked excitatory postsynaptic potentials (EPSPs) in
      motoneurones innervating hip, knee and ankle extensors. Disynaptic EPSPs were
      also evoked by selective activation of group Ia muscle spindle afferents by
      muscle stretch. 3. The central latencies of these group I-evoked EPSPs (mean,
      1.55 ms) suggest their mediation by a disynaptic pathway with a single
      interneurone interposed between extensor group I afferents and extensor
      motoneurones. Disynaptic EPSPs were also evoked during periods of spontaneous
      locomotion following the cessation of MLR stimulation. 4. Hip extensor
      motoneurones received disynaptic EPSPs during extension following stimulation of
      both homonymous and ankle extensor nerves. Stimulation of hip extensor nerves did
      not evoke disynaptic EPSPs in ankle extensor motoneurones. 5. The appearance of
      disynaptic EPSPs during extension appears to result from cyclic disinhibition of
      an unidentified population of excitatory spinal interneurones and not
      postsynaptic voltage-dependent conductances in motoneurones or phasic presynaptic
      inhibition of group I afferents during flexion. 6. The reorganization of group I
      reflexes during fictive locomotion includes the appearance of disynaptic
      excitation of hip, knee and ankle extensor motoneurones. This excitatory reflex
      is one of the mechanisms by which group I afferents can enhance extensor activity
      and increase force production during stance.

PMID- 8865082
TI  - Respiratory mechanics during exhaustive submaximal exercise at high altitude in
      healthy humans.
AB  - 1. The present investigation was conducted to test the hypothesis that the
      respiratory system is stressed more during exhaustive exercise in chronic hypoxia
      than in normoxia. 2. Four healthy male subjects (aged 33-35 years) exercised on a
      cycle ergometer at 75% of the local maximum oxygen consumption (Vo2,max) until
      exhaustion, at sea level (SL) and after a 1 month stay at 5050 m (HA). 3. Airflow
      at the mouth (V), oesophageal (Po) and gastric (Pg) pressures were measured at
      rest, during exercise and recovery. Minute ventilation (VE), respiratory power
      (Wresp), respiratory frequency (f) and transdiaphragmatic pressure (Pdi) were
      calculated from the measured variables. 4. The subjects' mechanical power output
      of cycling at HA was 23.7% lower than at SL. In spite of this reduction, time to
      exhaustion at HA was 55.3% less than at SL. VE increased slightly during exercise
      at SL, but showed a marked increase at HA, and at the end of exercise at HA was
      47.3% higher than at SL. 5. Respiratory power increased more at HA than at SL
      (77.3% higher at the end of exercise) due to the increase in f needed to sustain
      the high VE. 6. Gastric pressure swings were negative at the end of HA exercise
      but always positive at SL. The Pai:Po ratio reached values below 1 at HA but
      never at SL. 7. These data seem to indicate that the respiratory system is
      stressed more during submaximal exercise at HA than at SL. We suggest that the
      exceedingly high VE demand, requiring an excessive Wresp, may lead to fatigue of
      the diaphragm.

PMID- 8865081
TI  - Kinematic determinants of human locomotion.
AB  - 1. The aim of this study was to find kinematic patterns that are invariant across
      the normal range of locomotion speeds. Subjects walked at different, freely
      chosen speeds ranging from 0.9 to 2.1 m s-1, while motion and ground reaction
      forces on the right side of the body were recorded in three-dimensional space. 2.
      The time course of the anatomical angles of flexion-extension at the hip and
      ankle was variable not only across subjects, but even from trial to trial in the
      same subject. By contrast, the time course of the changes in the angles of
      elevation of each limb segment (pelvis, thigh, shank and foot) relative to the
      vertical was stereotyped across subjects. 3. To compare the waveforms across
      speeds, data were scaled in time relative to gait cycle duration. The pattern of
      ground reaction forces was highly speed dependent. Several distinct families of
      curves could be recognized in the flexion-extension angles at the hip and ankle.
      Instead, the waveforms of global length and elevation of the limb, elevation
      angles of all limb segments and flexion-extension at the knee were invariant with
      speed. 4. When gait trajectories at all speeds are plotted in the position space
      defined by the elevation angles of the limb segments, they describe regular loops
      on a plane. The statistical characteristics of these angular covariations were
      quantified by means of principal component analysis. The first two principal
      components accounted together for > 99% of the total experimental variance, and
      were quantitatively comparable in all subjects. 5. This constraint of planar
      covariation of the elevation angles is closely reminiscent of that previously
      described for the control of posture. The existence of laws of intersegmental co
      ordination, common to the control of posture and locomotion, presumably assures
      the maintenance of dynamic equilibrium during forward progression, and the
      anticipatory adaptation to potentially destabilizing factors by means of co
      ordinated kinematic synergies of the whole body.

PMID- 8865083
TI  - Eccentric exercise decreases maximal insulin action in humans: muscle and
      systemic effects.
AB  - 1. Unaccustomed eccentric exercise decreases whole-body insulin action in humans.
      To study the effects of one-legged eccentric exercise on insulin action in muscle
      and systemically, the euglycaemic clamp technique combined with arterial and
      bilateral femoral venous catheterization was used. Seven subjects participated in
      two euglycaemic clamps, performed in random order. One clamp was preceded 2 days
      earlier by one-legged eccentric exercise (post-eccentric exercise clamp (PEC))
      and one was without the prior exercise (control clamp (CC)). 2. During PEC the
      maximal insulin-stimulated glucose uptake over the eccentric thigh was marginally
      lower when compared with the control thigh, (11.9%, 64.6 +/- 10.3 vs. 73.3 +/-
      10.2 mumol kg-1 min-1, P = 0.08), whereas no inter-thigh difference was observed
      at a submaximal insulin concentration. The glycogen concentration was lower in
      the eccentric thigh for all three clamp steps used (P < 0.05). The glucose
      transporter GLUT4 protein content was on average 39% lower (P < 0.05) in the
      eccentric thigh in the basal state, whereas the maximal activity of glycogen
      synthase was identical in the two thighs for all clamp steps. 3. The glucose
      infusion rate (GIR) necessary to maintain euglycaemia during maximal insulin
      stimulation was lower during PEC compared with CC (15.7%, 81.3 +/- 3.2 vs. 96.4
      +/- 8.8 mumol kg-1 min-1, P < 0.05). 4. Our data show that 2 days after
      unaccustomed eccentric exercise, muscle and whole-body insulin action is impaired
      at maximal but not submaximal concentrations. The local effect cannot account for
      the whole-body effect, suggesting the release of a factor which decreases insulin
      responsiveness systemically.

PMID- 8865084
TI  - Mechanisms of activation of muscle branched-chain alpha-keto acid dehydrogenase
      during exercise in man.
AB  - 1. Exercise leads to activation (dephosphorylation) of the branched-chain alpha
      keto acid dehydrogenase (BCKADH). Here we investigate the effect of low pre
      exercise muscle glycogen content and of branched-chain amino acid (BCAA)
      ingestion on the activity of BCKADH at rest and after 90 min of one-leg knee
      extensor exercise at 65% maximal one-leg power output in five subjects. 2. Pre
      exercise BCAA ingestion (308 mg BCAAs (kg body wt)-1) caused an increased muscle
      BCAA uptake, a higher intramuscular BCAA concentration and activation of BCKADH
      both at rest (9 +/- 1 versus 25 +/- 5% for the control and BCAA test,
      respectively) and after exercise (27 +/- 4 versus 54 +/- 7%). 3. At rest the
      percentage active BCKADH was not different, 6 +/- 2% versus 5 +/- 1%, in the
      normal and low glycogen content leg (392 +/- 21 and 147 +/- 34 mumol glycosyl
      units (g dry muscle)-1, respectively). The post-exercise BCKADH activity was
      higher in the low (46 +/- 2%) than in the normal glycogen content leg (26 +/-
      2%). 4. It is concluded that: (1) the mechanism of activation by BCAA ingestion
      probably involves an increase of the muscle BCAA concentration; (2) BCKADH
      activation caused by exercise and BCAA ingestion are additive; (3) low pre
      exercise muscle glycogen content augments the exercise-induced BCKADH activation
      without an increase in muscle BCAA concentration; and (4) the mechanism of BCKADH
      activation via BCAA ingestion and low muscle glycogen content are different.

PMID- 8865085
TI  - Anteroposterior dynamic balance reactions induced by circular translation of the
      visual field.
AB  - The anteroposterior sway of subjects under conditions of spontaneous dynamic
      balance on a wobbly platform was measured during visual stimulation by a visual
      target executing a circular trajectory in the frontal plane. The target was
      either a component of the whole moving visual scene or moving on a stationary
      background. With the former stimulation, obtained through the use of rotating
      prismatic glasses, every point of the visual field appeared to describe a
      circular trajectory around its real position so that the whole visual field
      appeared to be circularly translated, undistorted, inducing a binocular pursuit
      movement. Under these conditions, stereotyped anteroposterior dynamic balance
      reactions synchronous with the position of the stimulus were elicited. The latter
      stimulation consisted of pursuing a luminous target describing a trajectory
      similar to that of the fixation point seen through the rotating prisms on the
      same, this time stable, visual background. Although pursuit eye movements were
      comparable, as demonstrated by electro-oculographic recordings, no stereotyped
      equilibration reaction was induced. It is concluded that the translatory motion
      of the background image on the retina in the latter experiments contributed to
      the body's stability as well as to the perception of a stable environment.

PMID- 8865086
TI  - Differences in action of topical and systemic cysteamine on gastric blood flow,
      gastric acid secretion and gastric ulceration in the rat.
AB  - The effect of cysteamine on gastric blood flow and on the indomethacin-induced
      gastric mucosal damage was studied. In anesthetized rats, cysteamine (280 mg/kg)
      given subcutaneously (s.c.) decreased gastric blood flow measured by the laser
      Doppler flowmetry technique. In contrast, cysteamine (1-60 mg/ml) applied
      topically to the serosal surface of the stomach evoked a concentration-dependent
      and long-lasting increase in gastric blood flow. At 60 mg/ml, cysteamine
      increased blood flow by 166.8 +/- 26.1% of predrug control value. Pretreatment
      with indomethacin (20 mg/kg, s.c.), intravenous (i.v.) atropine (1 mg/kg),
      propranolol (1 mg/kg, i.v.), combined H1 and H2-blockade or bilateral cervical
      vagotomy alone or combined with i.v. guanethidine (8 mg/kg), or pretreatment with
      the capsaicin analogue resiniferatoxin did not reduce the vasodilator response to
      cysteamine. The vasodilator response to topical capsaicin, was not reduced after
      s.c. cysteamine (280 mg/kg) pretreatment. In conscious pylonus-ligated rats, s.c.
      cysteamine (100 or 280 mg/kg) given simultaneously with indomethacin inhibited
      gastric acid output but had variable effects on the indomethacin-induced gastric
      mucosal damage. Cysteamine (100 or 280 mg/kg) administered s.c. 4 h prior to
      indomethacin enhanced gastric injury by s.c. indomethacin, but did not prevent
      the gastroprotective action of capsaicin. In contrast, orally administered
      cysteamine (60 mg/ml) reduced gastric injury induced by s.c. indomethacin plus
      intragastric HCl. These data provide the first evidence for the effect of
      cysteamine on gastric microcirculation in the rat and suggest a direct
      vasodilator effect for topical cysteamine. The microvascular effects of
      cysteamine are largely responsible for the different effects of this agent on
      experimental gastric injury.

PMID- 8865087
TI  - Axonal conduction velocity of motor units of rat's medial gastrocnemius muscle.
AB  - Axonal conduction velocity and its relations to different contractile properties
      of motor units of medial gastrocnemius muscle were investigated in nine Wistar
      rats anaesthetized with pentobarbitone. Functionally isolated motor units were
      identified as slow (S), fast resistant (FR) and fast fatigable (FF). Axons of S
      motor units conducted significantly more slowly than of fast units, while there
      was considerable overlap between conduction velocities measured for FR and FF
      types. The mean values of conduction velocity were 50.9 m/s for S, 68.9 m/s for
      FR and 71.3 m/s for FF type motor units. Strong and significant negative
      correlation between conduction velocity and contraction time as well as half
      relaxation time was demonstrated. However, only a weak correlation between
      conduction velocity and twitch tension, tetanic tension or fatigue index was
      found. The multiple regression analysis revealed that the major factor to
      determine conduction velocity was contraction time.

PMID- 8865088
TI  - NG methyl-L-arginine increases the hyperthermic effects of prostaglandin E1.
AB  - The sympathetic firing rate of the nerves innervating interscapular brown adipose
      tissue (IBAT), IBAT and colonic temperatures (TIBAT and TC) were monitored in
      urethane-anaesthetized male Sprague-Dawley rats. These variables were measured
      for a period of 40 min before (baseline values) and 40 min after a 2 mg NG-methyl
      L-arginine (NMA) injection plus an intracerebroventricular administration of 500
      ng prostaglandin E1 (PGE1) into a lateral cerebral ventricle. No drug was
      injected in control rats. The results show that NMA enhances the increases in
      firing rate, TIBAT and TC induced by PGE1. These findings indicate that an
      inhibitor of nitric oxide synthesis, such as NMA, increases the sympathetic and
      thermogenic responses to injection of PGE1.

PMID- 8865089
TI  - Head-activator induced mitosis of NH15-CA2 cells requires calcium influx and
      hyperpolarization.
AB  - In NH15-CA2 cells head activator (HA) stimulates cell proliferation by acting in
      the G2/M transition. Cells in mitosis were analyzed by flow cytometry 2-4 h after
      HA application. HA in a dose-dependent manner stimulated mitosis. Mitosis was
      prevented by preincubation of cells with pertussis toxin identifying the HA
      receptor as being Gi-protein coupled. As second effect of HA, an increase in
      intracellular calcium concentration was observed. This increase in calcium
      concentration was abolished by inhibiting calcium influx from the extracellular
      space into NH15-CA2 cells either by chelating extracellular calcium with EGTA or
      by blocking calcium channels. The increase in intracellular calcium concentration
      led to an activation of calcium-dependent potassium channels. The higher
      potassium conductance resulted in hyperpolarization of NH15-CA2 cells. Blocking
      calcium channels with nickel chloride or potassium channels with
      tetraethylammonium chloride inhibited the effect of HA on cell proliferation. HA
      induced mitosis was inhibited by charybdotoxin and apamin, but not by alpha
      dendrotoxin confirming the notion that Ca(2+)-dependent potassium channels are
      involved in mediating the effect of HA on cell division.

PMID- 8865090
TI  - Reference listings in integrative neuroscience.

PMID- 8865091
TI  - Laryngopharyngeal reflux: consensus conference report.

PMID- 8865092
TI  - Performance effects on the voices of 10 choral tenors: acoustic and perceptual
      findings.
AB  - Trained choral tenors performed a series of vocal tasks before and after a "live"
      performance. Acoustic (perturbation, harmonic-to-noise ratio, pitch and amplitude
      ranges) and perceptual analyses (auditory and proprioceptive/kinesthetic) were
      undertaken to detect changes from pre- to postperformance. Individuality of
      response to the performance was revealed, with the majority of subjects showing
      vocal deterioration after performance. The most sensitive vocal tasks were the
      comfortably pitched notes, high soft notes, and the bottom notes in scale
      singing. The most sensitive acoustic measure in detecting change from pre- to
      postperformance was harmonic-to-noise ratio. In contrast to the demonstrated
      acoustic changes, no significant differences in perceptual ratings were evident
      after the performance. Perceptual ratings did not reflect the acoustic analysis
      results. The present study highlights the need to establish further normative
      data for the singing voice and to consider individual differences in vocal
      characteristics in future studies of the singing voice.

PMID- 8865093
TI  - Singing power ratio: quantitative evaluation of singing voice quality.
AB  - This paper presents a parameter for objectively evaluating singing voice quality.
      Power spectrum of vowel sound /a/ was analyzed by Fast Fourier Transform. The
      greatest harmonics peak between 2 and 4 kHz and the greatest harmonics peak
      between 0 and 2 kHz were identified. Power ratio of these peaks, termed singing
      power ratio (SPR), was calculated in 37 singers and 20 nonsingers. SPR of sung
      /a/ in singers was significantly greater than in nonsingers. In singers, SPR of
      sung /a/ was significantly greater than that of spoken /a/. By digital signal
      processing, power spectrum of sung /a/ was varied, and the processed sounds were
      perceptually analyzed. SPR had a significant relationship with perceptual scores
      of "ringing" quality. SPR provides an important quantitative measurement for
      evaluating singing voice quality for all voice types, including soprano.

PMID- 8865094
TI  - Comparison of direct and indirect calculations of laryngeal airway resistance in
      connected speech.
AB  - Direct measures of subglottal pressure obtained through a tracheal puncture were
      used to calculate laryngeal airway resistance. Six subjects completed tasks
      including syllable trains and more natural speech samples produced at three
      loudness levels. Direct calculations of natural speech resistance values were
      compared with indirect estimates obtained during syllable train production. The
      degree of correspondence between direct and indirect calculations varied by
      subject. Overall, the smallest relative errors among calculations occurred for
      syllable trains, with higher relative errors for the monologue and sentence. For
      loudness conditions, the smallest and largest relative errors occurred for soft
      and loud productions, respectively. The clinical utility of indirect estimation
      is questioned and suggestions for improving its validity are provided.

PMID- 8865095
TI  - Speaking Fo and cepstral periodicity analysis of conversational speech in a 105
      year-old woman: variability of aging effects.
AB  - We investigated speaking fundamental frequency and periodicity of voicing during
      conversational speech in a 105-year-old woman. Analyses revealed higher mean
      speaking fundamental frequency compared to previously published data obtained
      from elderly women. In the absence of normative data, the results of cepstrum
      analyses performed on vowels produced during connected speech revealed less
      periodicity for the 105-year-old woman's voice than for a 35-year-old woman's
      voice. The main finding of this study indicates that previously reported group
      trends regarding aging effects on mean speaking fundamental frequency of the
      female voice cannot simply be attributed to all elderly individuals. These
      results stress the importance, for clinical and research purposes, of recognizing
      the existence of considerable intra- as well as intersubject variability in the
      effects of aging on the voice.

PMID- 8865096
TI  - Perturbation and hoarseness: a pilot study of six children's voices.
AB  - Fundamental frequency (FO) perturbation has been found to be useful as an
      acoustic correlate of the perception of dysphonia in adult voices. In a previous
      investigation, we showed that hoarseness in children's voices is a stable concept
      composed mainly of three predictors: hyperfunction, breathiness, and roughness.
      In the present investigation, the relation between FO perturbation and hoarseness
      as well as its predictors was analyzed in running speech of six children
      representing different degrees of hoarseness. Two perturbation measures were
      used: the standard deviation of the distribution of perturbation data and the
      mean of the absolute value of perturbation. The results revealed no clear
      relation.

PMID- 8865097
TI  - Sound level variation findings for pianissimo and fortissimo phonations in
      repeated measurements.
AB  - Ten vocally untrained female university students vocalized /a:/ at five given
      pitches within the average female speaking range (196, 220, 262, 330, and 396 Hz)
      as softly as possible (pianissimo) and as loudly as musically acceptable
      (fortissimo). To study the repeatability of voice range profile (sound level)
      measurement, the procedure was repeated 10 times in each of the five sample
      sessions during the day, in connection with vocal loading that included five oral
      readings (45 min each), 15-min pauses, and a lunch break (45 min). A sound level
      meter specially designed for voice range profile measurement was used. The effect
      of the loading was seen on the mean sound level changes and intraindividual
      variation on SDs. The difference between the first phonation and best performance
      indicates significance of the repetition of the measurement. The sound level
      averaged across the pitches rose significantly during loading. The
      intraindividual SD varied between 3 and 4 dBA according to pitch and loudness,
      and the sound level difference between the first phonation and best performance
      was approximately 5 dBA in pianissimo and approximately 7 dBA in fortissimo.

PMID- 8865098
TI  - Meaningful features of voice range profiles from patients with organic vocal fold
      pathology: a preliminary study.
AB  - This preliminary study identifies features that have the potential to be
      meaningful descriptors of voice range profiles (VRPs) for 15 patients with
      organic vocal fold pathologies before and after laryngeal surgery. This study
      also explores the utility of the VRP as an outcome measure of change in vocal
      function after surgery. Potentially meaningful features for these patients are
      the semitone range, intensity level of the lower contour, frequency locus of the
      lower frequency values, smoothness of the contours, and the presence of
      intermittencies in the VRP contours. These features are not suggested for
      differential diagnosis, but for aiding the understanding of each individual
      patient's phonatory status. Initial use of these features suggests that the VRP
      may be a useful outcome measure for these patients.

PMID- 8865099
TI  - Gender differences in children's intonational patterns.
AB  - This study investigated differences among intonational variables in prepubescent
      girls' and boys' voices in conversational speech (American-English). Subjects
      were middle class boys and girls at each of four age levels: 3-4, 5-6, 7-8, and 9
      10 years. Samples of conversational speech were recorded and acoustically
      analyzed for minimum and maximum FO, mean FO, and SD of FO (FOSD), as well as
      number and direction of FO changes ("shifts") per utterance. Findings indicated
      that the mean FO of the males decreased at around age 7-8 years. Additionally,
      maximum FO, range, and percentage of rising and falling shifts all showed
      decreases for the males starting at ages 7-8 not paralleled by decreases for the
      females. Both physiological and sociocultural factors appear to account for the
      changes that mark the development of intonational patterns in prepubertal girls
      and boys.

PMID- 8865100
TI  - Bridging the gap between theory and practice: a multimedia tutorial for students
      of voice therapy.
AB  - A computer-based tutorial for speech and language therapy students is described
      in which a digitized video-recording of a diagnostic interview with a voice
      disordered client was dynamically linked to an on-screen transcript window. A
      student-centered tutorial package, which provided guidance through questions,
      assessment tasks, and commentary from an experienced speech and language
      pathologist as well as the lecturer in voice disorder, was constructed.
      Evaluation of the tutorial as an aid to active learning, including feedback from
      students and supervising clinicians, is reported and the role of this type of
      program as a preparation for clinical practice is discussed.

PMID- 8865101
TI  - Comfortable effort level revisited.
AB  - The purpose of this study was to measure the variability of frequency and
      intensity of speech, using multiple voice samples obtained over a period of time
      at a speaker's "comfortable effort level." Variability in vocal output within and
      across several experimental sessions was assessed from measures of speaking
      fundamental frequency (SFF) and vocal intensity for utterances repeated three
      times a day over a 3-day period. Three distinct age groups of men and women
      young, middle-aged and elderly-repeated the vowel /a/, read a standard passage,
      and spoke extemporaneously during each experimental session. Results indicated
      that variability in SFF and intensity were present across experimental sessions,
      age groups, gender, and speaking samples. Generally, group means indicated that
      approximately +/- 1 semitone of variability for SFF and approximately 2 db sound
      pressure level (SPL) variation in vocal intensity from any one experimental
      session to the next could be expected; individual variations within any group may
      reach two semitones and 6 db SPL.

PMID- 8865102
TI  - Analysis of factors affecting botulinum toxin results in spasmodic dysphonia.
AB  - This study was designed to investigate how variations in patterns of injection
      could improve the efficacy of botulinum toxin injections in relieving the
      symptoms of adductor spasmodic dysphonia. A total of 64 adductor spasmodic
      dysphonia patients who were injected using indirect laryngoscopic localization
      (for a total of 426 injections) were analyzed retrospectively using their own
      subjective data on duration of voice improvement, optimal voice improvement,
      breathiness side effects, and intervals between treatments. Injection to both the
      thyroarytenoid (TA) and the lateral cricoarytenoid (LCA) simultaneously gave the
      best voice results; the overall improvement from baseline was the longest
      lasting, and the period during which the voice was the best was the longest
      lasting. TA+LCA also gave the shortest duration of undesirable breathiness side
      effect. On the basis of these data, it seems reasonable to recommend that initial
      botulinum toxin therapy for adductor spasmodic dysphonia patients should be a
      single unilateral injection placed strategically at the posterior portion of the
      TA and directed toward the LCA so that both muscle groups are affected.

PMID- 8865103
TI  - Posterior cordectomy and subtotal arytenoidectomy for the treatment of bilateral
      vocal fold immobility: functional results.
AB  - We report vocal and respiratory results following endoscopic CO2 laser therapy
      for bilateral vocal fold immobility in adduction. Two techniques were used:
      posterior cordectomy (PC) and subtotal arytenoidectomy (SA). Respiratory
      improvement was demonstrated by the peak expiratory flow/peak inspiratory flow
      ratio (PEF/PIF, normal = 1), which was less than 2 for 83% of patients following
      PC and for 81% following SA. As for vocal results, there were no significant
      quantitative differences between the two techniques. Mean maximum phonation time
      (/a/) was 6.8 +/- 2.6 s after SA and 7.8 +/- 1.6 s following PC. The phonation
      quotient was 288 +/- 116 ml/s after SA and 304 +/- 92 ml/s after PC. Mean vocal
      intensity was 62 +/- 4 dB after SA and 59 +/- 3 dB after PC. Vocal quality was
      measured by high-resolution vocal frequency analysis, as represented by a
      histogram. Peaks corresponding to fundamental frequency and first harmonics were
      preserved in more than 60% of patients in the two groups. Vocal preservation is
      better when the paralyzed folds are in the paramedian position, with the
      possibility of adduction (Gerhardt syndrome). SA is performed in our procedure,
      though it is longer and more difficult to perform than PC. PC often requires two
      procedures to achieve satisfactory results.

PMID- 8865104
TI  - In vivo crypt surface hyperproliferation is decreased by butyrate and increased
      by deoxycholate in normal rat colon: associated in vivo effects on c-Fos and c
      Jun expression.
AB  - BACKGROUND: Studies on colon carcinogenesis suggest that the short-chain fatty
      acid butyrate may be protective, whereas the secondary bile acid deoxycholate may
      promote tumor development. Crypt surface hyperproliferation is regarded as a
      biomarker of colon cancer risk and can be modulated in vitro by the
      differentiation inducer butyrate and the tumor promoter deoxycholate. We
      hypothesized that butyrate decreases and deoxycholate increases crypt surface
      proliferation in vivo and that these effects are mediated by changes in the
      expression of the protooncogenes c-Fos and c-Jun, which are known to regulate
      proliferation and differentiation. METHODS: Twenty-five adult Sprague-Dawley rats
      underwent colonic isolation and 24-hour intraluminal instillation of 10 mmol/L
      sodium chloride, 10 mmol/ L sodium butyrate, or 10 mmol/L sodium deoxycholate.
      Proliferation of the whole crypt and five crypt compartments from base to surface
      was assessed by proliferating cell nuclear antigen immunohistochemistry. The oh
      value, an index of "premalignant" hyperproliferation, was calculated as the ratio
      of labeled cells in the two surface compartments divided by the labeled cells in
      the entire crypt. Expression of c-Fos and c-Jun was evaluated by Western blot.
      RESULTS: Crypt surface proliferation and the oh value were significantly
      decreased by butyrate and increased by deoxycholate. Butyrate increased colonic
      expression of c-Jun, whereas deoxycholate significantly induced c-Fos.
      CONCLUSIONS: The in vivo effects on surface proliferation are consistent with a
      potential protective [corrected] role for butyrate and a promotive role for
      deoxycholate in colon carcinogenesis. The concurrently observed effects on
      colonic c-Jun and c-Fos expression represent a novel finding and suggest that
      direct or indirect modulation of protooncogene expression may be the mechanism by
      which these dietary byproducts regulate proliferation in vivo.

PMID- 8865105
TI  - Effects of succinic acid dimethyl ester infusion on metabolic, hormonal, and
      enzymatic variables in starved rats.
AB  - BACKGROUND: Succinic acid dimethyl ester (SAD) is efficiently metabolized in
      several cell types as pancreatic islet cells, hepatocytes, and colonocytes. The
      purpose of this study was to assess the overall nutritional value of SAD in the
      whole organism. METHODS: SAD was infused at a rate of 80 micromol/g body weight
      per day in rats starved for either 2 or 4 days. For comparison, similar
      experiments were conducted in starved rats receiving an equimolar infusion of D
      glucose. RESULTS: The ester failed to prevent the starvation-induced fall in body
      weight, paraovarian fat mass, and liver or muscle protein content. The infusion
      of SAD minimized, however, the decrease in plasma glucose and insulin
      concentrations, liver glycogen content, hepatic glucokinase activity, and islet
      secretory responsiveness to glucose, otherwise caused by starvation. Likewise,
      the infusion of SAD delayed the rise in free fatty acid and beta-hydroxybutyrate
      plasma concentration occurring during starvation. Nevertheless, SAD was less
      efficient than glucose, infused in an equimolar amount, in preventing the
      starvation-induced fall in liver glycogen content, decrease in the pancreatic B
      cell secretory responsiveness to glucose, and stimulation of lipolysis and
      ketogenesis. CONCLUSIONS: SAD displays a significant nutritional value when
      infused in starved rats. It could thus be used as a tool to prevent the imbalance
      between ATP generation and use in selected metabolic situations.

PMID- 8865106
TI  - Metabolic and respiratory effects of sodium lactate during short i.v. nutrition
      in critically ill patients.
AB  - BACKGROUND: Hyperglycemia and an increased ventilatory demand secondary to an
      increased CO2 production are frequent undesirable effects of total parenteral
      nutrition (TPN) in critically ill patients. This study was performed to assess
      whether sodium lactate as a metabolic substrate may affect these variables.
      METHODS: Five male patients with multiple trauma during the flow phase were
      studied during two consecutive 3-hour periods of isocaloric (1.1 x resting energy
      expenditure) TPN. Sixty-five percent of total calories was provided as
      carbohydrate, 15% as lipids, and 20% as amino acids during the first period (TPN
      glucose), whereas 35% carbohydrate, 30% lactate, 20% lipids, and 15% amino acids
      (TPN-lactate) were substituted during the second period. Respiratory gas
      exchanges and net substrate oxidation were assessed by means of indirect
      calorimetry. Glucose kinetics was determined by primed-constant infusion of U-13C
      glucose. RESULTS: Compared with TPN-glucose, TPN-lactate decreased glycemia by
      20%, insulinemia by 43%, net carbohydrate oxidation (assessed from indirect
      calorimetry) by 34%, and plasma glucose oxidation (assessed from 13CO2) by 54%.
      Respiratory oxygen exchange were increased by 3.7% due to a 20% thermic effect of
      lactate, but respiratory CO2 exchanges did not change. Pao2 decreased by 11.3 mm
      Hg, indicating that the increased O2 consumption was not matched by an
      appropriate increase in spontaneous ventilation. Arterial pH increased from 7.41
      +/- 0.04 to 7.46 +/- 0.05. CONCLUSION: Sodium lactate as a metabolic substrate
      limits hyperglycemia but induces metabolic alkalosis and does not spare the
      ventilatory demand.

PMID- 8865107
TI  - Short-chain fatty acid-supplemented total parenteral nutrition improves
      nonspecific immunity after intestinal resection in rats.
AB  - BACKGROUND: Total parenteral nutrition (TPN) alters both specific and nonspecific
      immune functions, resulting in immunosuppression. Short-chain fatty acids have
      been shown to improve the adaptive responses of the gut after surgery. The
      following study investigates the effects of adding short-chain fatty acids to TPN
      on the immune system after an 80% small bowel resection. METHODS: Rats (237 +/- 3
      g) were infused with either TPN (n = 25) or TPN supplemented with short-chain
      fatty acids (n = 26) for 3 or 7 days. Hematologic analysis was performed on
      peripheral blood and splenocytes were isolated to characterize cell phenotypes,
      natural killer cell cytotoxicity and to estimate proliferative response. RESULTS:
      The relative percent of T (CD3+) cells increased (p < .05) and the relative
      percent of macrophages decreased (p < .001, n = 13) in the spleens of the 3-day
      TPN-fed rats. By day 7, these differences disappeared. The natural killer cells
      from rats that were supplemented with short-chain fatty acids had higher (p <
      .0001) cytotoxic activity than the TPN groups at day 3. Mitogenic response did
      not differ between groups but were depressed compared with sham-treated rats. By
      day 7, rats on standard TPN had larger (p < .0001) spleens than all other groups.
      This group also had a higher total white blood cell count because of increased
      numbers of macrophages and neutrophils (p < .02). CONCLUSION: Short-chain fatty
      acids improve components of nonspecific immune responses and may be beneficial in
      reducing certain aspects of TPN-associated immunosuppression after major surgery.

PMID- 8865108
TI  - Reducing the inappropriate use of parenteral nutrition in an acute care teaching
      hospital.
AB  - BACKGROUND: Parenteral nutrition (PN) is a form of nutrition that can be life
      saving, but its use has inherent risks and it is expensive. Nutrition support
      teams have been shown to reduce both the rate of complications and excessive use
      of PN. METHODS: Criteria were established to evaluate the appropriateness of PN
      use in a 487-bed community teaching hospital. A prospective study of 50
      consecutive patients, who received either central or peripheral PN, was
      conducted. RESULTS: The 50 patients received 469 days of PN. We found that 233
      (49.7%) of the 469 days of PN were avoidable. This resulted in the creation of a
      formal approval process that required prior approval by a physician-directed
      multidisciplinary advisory committee before PN could be instituted. The amount of
      PN subsequently decreased from 500 patient days of PN per month to less than 100.
      CONCLUSIONS: This study supports the idea that inappropriate use of PN can be
      reduced by physician education plus the continuing oversight of a physician
      directed multidisciplinary advisory group.

PMID- 8865109
TI  - The role of anatomic factors in nutritional autonomy after extensive small bowel
      resection.
AB  - BACKGROUND: It is difficult to predict which patients with a postsurgical short
      bowel will require long-term parenteral nutrition. METHODS: We performed a
      retrospective prognostic study for the time to home parenteral nutrition or death
      from malnutrition (nonautonomy), on the basis of 103 patients with a residual
      short bowel of 17 to 150 cm. The influence of anatomic variables was summarized
      through the use of Cox regression model. RESULTS: Of the 103 patients included,
      24 lost nutritional autonomy. Three anatomic variables were identified as having
      independent predictive information; remaining small bowel length (measured on
      small bowel x-rays; p = .0001), and jejunoileal anastomosis (p = .01) promoted
      autonomy, whereas end jejunostomy (p = .002) increased the risk of losing
      nutritional autonomy. CONCLUSIONS: On the basis of these results and on the
      relative weight of these variables, high-risk patients for loss of nutritional
      autonomy were defined as those with jejunoileal anastomosis and a remaining small
      bowel length < 35 cm, patients with jejunocolic anastomosis and remaining small
      bowel length < 60 cm, and patients with an end jejunostomy and remaining small
      bowel length < 115 cm. This classification was thereafter validated on a
      prospective series of 32 patients.

PMID- 8865110
TI  - Cerebrospinal and plasma amino acid concentrations after administration of i.v.
      glycyl-glutamine and glycyl-tyrosine containing amino acid solutions in humans.
AB  - BACKGROUND: Glycyl-glutamine and glycyl-tyrosine may supply adequate glutamine
      and tyrosine in amino acid solutions for parenteral nutrition. However, plasma
      peptides may be transported into the cerebrospinal fluid, exerting effects on the
      neuronal tissue. Cerebrospinal fluid (CSF) and plasma amino acid concentrations
      after administration of a glycyl-glutamine/glycyltyrosine supplemented amino acid
      solution were therefore evaluated in a randomized controlled comparison with a
      conventional amino acid infusion. METHODS: Dipeptide/amino acid solutions (0.60
      mL/h/kg; 82.2 mg total dipeptides/amino acids/h/kg) or conventional amino acid
      solutions (0.73 mL/h/kg; 83.2 mg total amino acids/h/kg) were infused in 15
      patients per group scheduled to undergo spinal anesthesia for urologic surgery
      over a 12-hour period preoperatively. Plasma amino acids were measured before the
      infusion was started. CSF and venous concentrations were analyzed simultaneously
      before the infusion was stopped. CSF samples were drawn through the spinal needle
      for anesthesia. RESULTS: The dipeptide-containing solution did not increase
      either dipeptide to detectable levels in the CSF (detection limit < 5.0 nmol/mL).
      Venous glycyl-glutamine increased from below detection limits up to 308 +/- 111
      nmol/mL (p < .05), whereas glycyl-tyrosine could not be found. In the dipeptide
      group, venous glutamine and tyrosine were higher (p < .05) but only tyrosine
      appeared in small amounts (p < .05) in the cerebrospinal fluid. CONCLUSIONS: This
      study provides no evidence to support a CSF entry of IV glycyl-tyrosine and
      glycyl-glutamine under conditions of a normal blood-brain barrier in the adult
      (detection limit 5 nmol/mL). The data suggest that amino acid solutions
      containing these dipeptides may be used in parenteral solutions for nutrition
      support.

PMID- 8865111
TI  - Selenoprotein P in patients on home parenteral nutrition.
AB  - BACKGROUND: The purpose of this study was to evaluate the use of selenoprotein P
      as an indicator of selenium status in patients receiving home parenteral
      nutrition. METHODS: Adult patients (n = 38) who had been on parenteral nutrition
      with no addition of selenium for 3 to 216 months were included in the study.
      Plasma samples were analyzed for selenium, selenoprotein P, and extracellular
      glutathione peroxidase (eGSHPx) using fluorimetry and newly developed
      radioimmunoassays. RESULTS: The mean plasma (+/- SD) eGSHPx and selenoprotein P
      in the patients were 1.9 +/- 1.2 mg/L and 0.7 +/- 0.4 arbitrary units,
      respectively, which corresponds to about 50% of the concentration measured in the
      plasma of the reference subjects (4.0 +/- 1.0 mg/L and 1.50 +/- 0.17 arbitrary
      units). The mean plasma selenium concentration was 0.5 +/- 0.4 mumol/L, which was
      approximately half of the concentration measured in the healthy subjects (1.1 +/-
      0.2 mumol/L). Thirty-four (89%) and 20 (53%) patients, respectively, had
      selenoprotein P and eGSHPx values lower than mean - 2 SD of the reference
      material. The lowest values observed for selenoprotein P and eGSHPx were 3% and
      2% of the reference mean. Selenoprotein P levels correlated significantly to
      eGSHPx (p = 0.88, p < .0001) and plasma selenium (p = 0.91, p < .0001).
      CONCLUSIONS: The positive correlations between selenoprotein P and eGSHPX and
      plasma selenium indicates that selenoprotein P may be used as a marker of
      selenium status in selenium-depleted patients.

PMID- 8865112
TI  - Glutamine content of protein and peptide-based enteral products.
AB  - BACKGROUND: Glutamine is a conditionally essential amino acid for patients with
      severe catabolic illness, intestinal dysfunction, or immunodeficiency syndromes.
      Glutamine is a natural component in many enteral preparations, yet lacking
      methodology hampers its quantitative determination in dietary products.
      OBJECTIVE: The present study was assigned to assess glutamine contents in
      selected enteral products by using a newly developed method enabling the
      assessment of protein/peptide bound glutamine. METHODS: Fourteen commercially
      available enteral diets (10 protein based and 4 peptide based) were investigated.
      After removal of interfering fat and carbohydrates, the nitrogen content of the
      purified preparations was determined by chemiluminescence and protein/peptide
      bound glutamine was assessed using a three-step procedure; by using a novel
      prehydrolysis derivatization technique with bis(1,1-trifluoroacetoxy)iodobenzene,
      glutamine is converted to acid stable diaminobutyric acid. The derivatives are
      hydrolyzed with a new microwave technology, and subsequently the amino acid
      composition is determined by reversed phase-high-performance liquid
      chromatography after dansyl-chloride derivatization. RESULTS: The content in the
      protein-based preparations varied between 5.2 and 8.1 g/16 g nitrogen. In the
      peptide-based products, considerably lower glutamine contents were measured (1.3
      to 5.6 g/16 g nitrogen). CONCLUSION: In the present study, we report for the
      first time glutamine contents in ready to use enteral products. The daily amount
      might be satisfactory for healthy individuals but probably not sufficient for the
      adequate support of the stressed patient. Reliable assessment of glutamine in
      enteral formulae is a prerequisite t perform clinical studies investigating
      glutamine requirements in the catabolic state.

PMID- 8865113
TI  - Effects of in-line filtration on lipid particle size distribution in total
      nutrient admixtures.
AB  - BACKGROUND: The recent Food and Drug Administration Safety Alert recommends in
      line filtration for all total parenteral nutrition admixtures. Although rigid
      crystalline particulates can be effectively removed by in-line filters, the fate
      of flexible lipid droplets (LDs) enlarged through electromechanical
      destabilization is less clear. Lipid globules > 5 microns could lodge in the
      pulmonary microvasculature and produce an embolic syndrome. Recent evidence
      suggests that TNAs (Total Nutrient Admixtures) with LDs of 5 microns or more
      constituting > 0.4% of the final fat concentration are unstable. METHODS: Six
      pairs of 1.5-L TNA dispersions of varying degrees of stability were prepared in
      duplicate (n = 12) and studied over 30 hours. The number of enlarged fat globules
      was assessed by laser light extinction for all LDs > or = 1.75 microns at 0, 6,
      24, and 30 hours after preparation. After LD assessments at time 0, admixtures
      were placed in a temperature-controlled chamber at 25 degrees C +/- 0.1 degree C.
      At 6 hours, a simulated patient infusion was begun using a 1.2-microns filter at
      a continuous flow rate of 55 mL/h. Pre- and postfiltration samples were taken at
      6, 24, and 30 hours, equal to times 0, 18, and 24 hours of the simulated
      infusion. A repeated measure two-way analysis of variance assessing treatment and
      time was performed. Dependent variable analyses included number-weighting of fat
      globules as > 5 microns (LD1), total number > or = 1.75 microns (LD2), LD1-LD2
      ratio (as %), and volume-weighted percent of fat (PFAT) > 5 microns. RESULTS: In
      all cases, time was a significant factor and was an expected finding as the
      stability of all extemporaneously prepared admixtures deteriorates with time. Of
      the number-weighted variables, a significant postfiltrate reduction was observed
      in LD1 (p = .041), LD2 (p < .001), and LD1-LD2 ratio (p < .0001). Of greatest
      clinical importance, the volume-weighted PFAT > 5 microns was significantly
      reduced by the in-line filter (p = .029). CONCLUSIONS: The TNA1 1.2-microns
      filter significantly reduced the total number and concentration of enlarged fat
      globules. The higher LD1-LD2 ratio may reflect the effects of filtration on
      electrically destabilized fat globules. However, total exposure to unstable and
      very large LDs was significantly reduced, suggesting that in-line TNA filtration
      should be a standard part of nutrition therapy.

PMID- 8865114
TI  - Risk of symptomatic central venous thrombotic complications in AIDS patients
      receiving home parenteral nutrition.
AB  - BACKGROUND: The acquired immunodeficiency syndrome (AIDS) is frequently
      complicated by malnutrition that may require parenteral nutritional support. In a
      non-AIDS population with long-term indwelling central venous catheters, low-dose
      warfarin therapy has been shown to prevent venous thrombosis. The purpose of this
      study was to determine the incidence of symptomatic central venous thrombosis in
      AIDS patients receiving home parenteral nutrition. The incidence of thrombosis on
      low-dose warfarin was compared with no prophylactic therapy. METHODS: A
      retrospective review of 47 malnourished AIDS patients started on home parental
      nutrition was performed. None of the patients had a prior history of venous
      thrombosis. During this period, 9 of 47 patients were treated with low-dose
      warfarin therapy. The incidence of clinical and radiologic venous thrombosis was
      compared in these two groups. RESULTS: Forty-seven patients were treated with
      parenteral nutrition for 296 patients-months. The rate of central venous
      thrombosis in patients receiving warfarin (0.016 thromboses per patient-month)
      was no different from those patients on no prophylactic therapy (0.009 thromboses
      per patient-month). The most common abnormality in coagulation observed in the
      entire group during follow-up was thrombocytopenia occurring in 66% of patients.
      Sixty percent of patients received medications that could interfere with platelet
      function. CONCLUSIONS: We conclude that routine thrombosis prophylaxis with low
      dose warfarin may not be justified in malnourished AIDS patients receiving home
      parenteral nutrition. Prospective clinical trials are needed to determine the
      risks and benefits of prophylactic warfarin therapy in this group of patients.

PMID- 8865115
TI  - The difficult-to-place feeding tube: successful endoscopic placement using a
      mucosal clip.
AB  - BACKGROUND: Delivery of enteral feeding beyond the ligament of Treitz is often
      desirable, as it diminishes enterogastric reflux and potential for pulmonary
      aspiration of enteral feeding solution. However, standard or fluoroscopically
      guided techniques often fail. We describe three such cases in which enteral
      feeding tube placement was achieved endoscopically and secured using an
      endoscopic clip-fixing device. METHODS: A standard feeding tube attached to a
      mucosal clip by a silk suture was advanced endoscopically into the small
      intestine. Using a through-the-endoscope clip-fixing device, the tube was
      attached to the bowel wall. RESULTS: Three patients underwent the above
      procedure: a postgastrectomy patient with a functionally obstructed jejunal pouch
      and a previously failed fluoroscopically guided placement had a nasojejunal
      feeding tube successfully placed beyond the obstruction: a cancer patient with
      duodenal obstruction due to SMA syndrome, a surgical gastrostomy, and a
      previously failed fluoroscopic attempt had a dual lumen pergastrostomy feeding
      tube placed beyond the obstruction; and a patient with a refractory benign
      esophageal stricture underwent esophageal dilation followed by successful feeding
      tube placement into the proximal jejunum. In all patients, the tube functioned
      well without subsequent occlusion or dislodgement. CONCLUSIONS: Endoscopic
      placement of feeding tubes using a clip-fixing device is a useful technique in
      patients with normal and abnormal anatomy in whom reliable delivery of enteral
      feeding beyond the ligament of Treitz is desired.

PMID- 8865116
TI  - Effect of abrupt discontinuation of high glucose infusion rates during parenteral
      nutrition.

PMID- 8865117
TI  - Migration of a metal connecting piece of a repaired Hickman catheter associated
      with infection.

PMID- 8865118
TI  - Manganese supplementation during TPN.

PMID- 8865119
TI  - Aspects of the epidemiology of lung cancer in smokers and nonsmokers in the
      United States.
AB  - While it is well-established that smoking is the predominant risk factor for lung
      cancer, it is clear that factors other than smoking and occupational exposure
      play a role in some lung cancers, and particularly adenocarcinoma. Data from a
      large, hospital-based case-control study are used to examine the association of
      smoking-related risk factors (amount smoked, filter status, mentholation, and
      differences in smoking habits between blacks and whites) and selected factors
      other than smoking (environmental tobacco smoke, previous primary cancer and
      radiotherapy, reproductive and endocrine factors, and body mass index) with lung
      cancer. Although smoking shows a dose-response relationship with all major lung
      cancer cell types, the strength of the relationship is weaker for adenocarcinoma,
      suggesting that other risk factors must play an important role for this cell
      type. In blacks and whites of both sexes, odds ratios for lung cancer increased
      with increasing cumulative tobacco tar intake and decreased with years since
      quitting smoking. Use of mentholated cigarettes was associated with no greater
      risk for lung cancer than that associated with the use of nonmentholated
      cigarettes. Exposure to environmental tobacco smoke generally showed little
      relation to lung cancer risk. In particular, exposure of nonsmoking wives to a
      husband's smoking showed no increase in risk. A history of a reproductive primary
      cancer and a history of radiotherapy were each associated with a fourfold
      increase in risk in female nonsmokers. An association of lean body mass with lung
      cancer was observed in current smokers, ex-smokers, and female never smokers.
      These results are discussed in the context of existing studies. In conclusion,
      variation in lung cancer rates between populations may be due to: (1) differences
      in effective exposure to tobacco smoke carcinogens; (2) differences in factors
      which modify the effect of tobacco smoke, including differences in host
      susceptibility and metabolism of carcinogens, or (3) differences in exposure to
      other independent risk factors for lung cancer.

PMID- 8865120
TI  - Long-term survival of patients with lung cancer from a defined geographical area
      before and after radiological screening.
AB  - In the County of Uppsala, Sweden, a general health survey including a chest
      roentgenogram was operational from the late 1960s until the end of June, 1985.
      The screening was offered every 2 years and participation was about 70%. From the
      local cancer registry all cases of lung cancer during the period 1980-1990 aged
      75 or less were obtained and their survival and mode of discovery investigated.
      Only WHO I-IV and undifferentiated cancers verified histologically were included.
      Twenty-eight cancers (11.5%) were discovered in the survey and these patients had
      a very good prognosis compared to those who presented with symptoms. During the
      health survey there were 35 of 244 (14.3%) who survived more than 4 years, and
      after the survey this figure was 34 out of 265 (12.8%), a nonsignificant
      difference. Survival for patients with squamous cell carcinoma or adenocarcinoma
      discovered in the health survey was much improved, and for these two groups
      combined the 4-year survival was 41.7% compared to 10.3% for those discovered by
      symptoms (P < 0.001). Thus, survival of patients with lung cancer of squamous
      cell or adenocarcinoma types can be improved by screening, but unfortunately,
      only few of the cancers will be discovered in this way, so the total impact of
      screening will be small.

PMID- 8865121
TI  - Expression of bcl-2--protein in small cell lung cancer.
AB  - The expression of the proto-oncogene bcl-2, whose main function appears to be an
      inhibition of apoptosis, was investigated in 164 cases of primary small cell lung
      cancer by means of immunohistochemistry in a retrospective analysis. One-hundred
      twenty-five cases (76%) demonstrated expression of bcl-2. There was no difference
      in serum LDH levels and proliferative activity between the two groups. An
      analysis revealed a median survival time of 12 months for patients with bcl-2
      positive tumors compared to 9.5 months for patients with bcl-2 negative tumors.
      Although statistical significance is not achieved, there is a trend towards
      longer survival in patients whose tumors express bcl-2. This tendency is also
      reflected by a higher rate of complete remission after chemotherapy: 40% in
      patients with bcl-2+ tumors versus 27% in patients with bcl-2- tumors. In
      multivariate analysis, tumor stage followed by Karnofsky index were the most
      valuable predictors for complete remission. LDH and tumor stage were most
      predictive for 1-year survival. Bcl-2 expression is frequent in SCLC and may
      reflect a less aggressive mechanism of transformation and a higher susceptibility
      to cytostatic treatment.

PMID- 8865122
TI  - KM195 as an immunohistochemical marker of adenocarcinoma of the lung.
AB  - In order to improve the diagnosis of lung carcinoma, in which a complicated
      histologic pattern is present, the immunohistochemistry of 119 adenocarcinomas,
      65 squamous cell carcinomas, 12 small cell carcinomas, 18 large cell carcinomas,
      and 15 metastatic adenocarcinoma in the lung were evaluated using a monoclonal
      antibody, KM195, against lung carcinoma, and compared with the
      immunohistochemical results using anti-human cytokeratin (CAM 5.2) and other
      monoclonal antibodies. Formalin-fixed, paraffin-embedded tissues were stained
      using the labeled streptavidin-biotin method. Extracts from fresh tissue
      homogenate, after fractionation by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, were transferred by Western blotting and stained with KM195. The
      anti-lung adenocarcinoma, murine, monoclonal antibody KM195 (IgG), was positive
      in 107 of 119 adenocarcinomas (90%), in 15 of 18 large cell carcinoma (83%), in
      three of 65 squamous cell carcinomas (5%), 13 of 15 (87%) metastatic
      adenocarcinoma in the lung, and was negative in 12 small cell carcinomas (P <
      0.001). KM195-bound protein of primary and metastatic adenocarcinoma in the lung
      cases concentrated at about 40 kDa. In contrast, CAM 5.2 was positive in 52 of 67
      (78%) adenocarcinomas, 10 of 62 (16%) squamous cell carcinomas, and was negative
      in six small cell carcinomas. These results suggest that the immunohistochemistry
      for KM195 may be a more useful marker over CAM 5.2 for the diagnosis of pulmonary
      adenocarcinoma.

PMID- 8865123
TI  - Chromosomal 11 alterations in non-small-cell lung carcinomas in Hong Kong.
AB  - We examined 60 non-small-cell lung cancer (NSCLC) patients for evidence of
      genetic alterations on chromosome 11 with nine polymorphic markers by Southern
      blot and microsatellite marker analysis. These analyses detected genetic
      alterations at both the 11p and 11q arms. At the 11p15 Ha-ras locus, the loss of
      heterozygosity (LOH) occurred in three out of 11 (27.3%) of the informative
      cases; at the 11p11-q12 D11S149 locus, the LOH occurred in two out of nine
      (22.2%) of the informative cases; and at the 11q13 INT-2 locus, the LOH occurred
      in four out of 18 (22.2%) of the informative cases. Microsatellite markers in the
      11q12-q13 region revealed genetic alterations for PYGM in eight out of 54 (14.8%)
      of the specimens studied and 10 out of 55 (18.2%) of the specimens for the INT-2
      marker. The data suggest genetic alterations occur in some of the lung cancer
      patients in both the 11p and 11q regions.

PMID- 8865124
TI  - Prognostic factors for patients with advanced non-small cell lung cancer:
      univariate and multivariate analyses including recursive partitioning and
      amalgamation.
AB  - In an attempt to determine the prognostic significance of pretreatment factors
      for patients with advanced non-small cell lung cancer (NSCLC), 24 pretreatment
      clinical variables were analyzed for 185 patients with NSCLC who underwent
      chemotherapy and/or radiotherapy between 1985 and 1994. Following univariate
      analysis, we applied two multivariate statistical techniques. In a Cox regression
      mode, independently significant factors influencing patient survival included
      performance status (PS), disease stage, hemoglobin level, and serum calcium
      level. Recursive partitioning and amalgamation (RPA) resulted in three distinct
      prognostic subgroups based on PS, stage, weight loss, and hemoglobin level. The
      best survival was observed for patients with a good PS and Stage III disease who
      had a hemoglobin level > 11 g/dl. The worst survival was observed for patients
      with a poor PS and presence of weight loss irrespective of stage. All other
      patients had an intermediate prognosis. Median survival times were 95.1 weeks,
      17.1 weeks and 39.3 weeks, respectively (P < 0.00005). The results of our
      analyses show that three important prognostic subgroups could readily be
      discerned using RPA.

PMID- 8865125
TI  - The clinical significance of serum soluble interleukin-2 receptors in lung
      cancer.
AB  - It has been recently reported that the soluble interleukin-2 receptor (IL-2R)
      levels in the sera of cancer patients were higher than those of normal controls.
      The present study was conducted in order to clarify the clinical significance of
      serum soluble IL-2R in patients with lung cancer. Using commercially available
      EIA kits, we measured the serum levels of soluble IL-2R in 102 lung cancer
      patients and 18 normal controls. The serum level of IL-2R was higher than 100 pM
      (mean +3 S.D. in the normal controls) in 14 of 58 patients with adenocarcinoma
      and in 13 of 32 patients with squamous cell carcinoma. In both adenocarcinoma and
      squamous cell carcinoma, the mean level of soluble IL-2R was higher in advanced
      stages (Stages IIIA, IIIB and IV) than in early stages (Stages I and II). In
      contrast, no patients with small cell carcinoma exhibited a serum level of
      soluble IL-2R higher than 100 pM, whereas almost all of those patients were in
      advanced-stage diseases. These results first demonstrated that the serum level of
      soluble IL-2R increased in association with both the disease stage and the
      histological type in lung cancer.

PMID- 8865126
TI  - Hyperfractionated radiotherapy and concomitant cisplatin in stage III non-small
      cell lung cancer: a phase II study by the AIRO-Lombardia Cooperative Group.
AB  - A multicenter Phase II study was performed by the AIRO-Lombardia Cooperative
      Group on 36 patients with Stage III non-small cell lung cancer. The treatment
      schedule included hyperfractionated radiotherapy, 1.2 Gy twice daily (5
      days/week) up to a total dose of 69.6 Gy, and concomitant cisplatin by continuous
      infusion using a portable pump, 16 mg/m2/week for 6 weeks. Overall, adequate
      treatment (defined as a total dose > 66 Gy in < 46 days and 6 weeks of infusional
      cisplatin) was received by 56% of accrued patients. Response was complete in 6%
      and partial in 56% of patients; median survival was 8 months and 1-year survival
      rate was 37%. Site of first failure was local in 43%, distant in 43%, local and
      distant in 10% and unknown in 3% of failing patients. Grade 3 esophagitis was
      recorded in 14% of patients and a fatal case of late pulmonary toxicity was
      reported. On the basis of feasibility, toxicity and survival results, the planned
      extension to Phase III was abandoned by the Group.

PMID- 8865127
TI  - Etoposide and doxorubicin antagonize the in vitro activity of paclitaxel in human
      non-small cell lung cancer cell lines.
AB  - GOAL: To explore in vitro interactions of paclitaxel with other agents also
      active against non-small cell lung cancer in the hope of identifying promising
      combinations for clinical evaluation. METHODS: We measured the cytotoxic effects
      of paclitaxel when used alone or in combination with vinblastine, cisplatin,
      etoposide or doxorubicin in final concentrations covering 3-4 Logs in up to five
      cell lines using a 96-well plate MTT assay. Drug interactions were analyzed with
      the isobologram method of Steel and Peckham and bidimensional plots. RESULTS: We
      detected no interactions between paclitaxel and cisplatin in two cell lines.
      Despite sharing a molecular site of action, there were no interactions between
      paclitaxel and vinblastine in two cell lines. In contrast, significant antagonism
      was detected between paclitaxel and etoposide or doxorubicin in 4/5 cell lines
      tested. CONCLUSIONS: We failed to identify potentially synergistic paclitaxel
      based combinations for the treatment of non-small cell lung cancer. Whether the
      observed in vitro antagonism between paclitaxel and etoposide or doxorubicin
      predicts for similar interaction in the clinical use of these drugs in
      combination is unknown.

PMID- 8865128
TI  - Partial substitution of cisplatin with carboplatin in combination with etoposide
      in advanced non-small cell lung cancer (NSCLC): a multicentric randomised phase
      II trial.
AB  - Seventy previously untreated patients with advanced NSCLC were randomised, after
      stratification for stage (IIIB vs. IV) and Performance Status (0-1 vs. 2), to
      receive either treatment A: CDDP 40 mg/m2 + VP16 100 mg/m2 day 1-3 (37 patients);
      or treatment B: CBDCA 250 mg/m2 day 1 + CDDP 30 mg/m2 day 2, 3 + VP16 100 mg/m2
      day 1-3 (33 patients). Therapy was recycled on day 29 in both arms. The two arms
      were well balanced for the main pretreatment characteristics. Sixty-six patients
      (32 with Stage IIIB and 34 with Stage IV disease) were evaluable for toxicity and
      response (arm A = 34, arm B = 32), while four ineligible patients were excluded
      from analysis. Acute toxicity was assessed at recycling. Non-hematologic toxicity
      was higher in arm A. However, the reduction of nephrotoxicity (9% vs. 23%) in arm
      B was lower than expected. Leukopenia (15 vs. 5 patients) or thrombocytopenia (7
      vs. 0 patients) of any grade affected more patients of arm B. Moreover, Grade 3-4
      leukopenia (six patients) or thrombocytopenia (four patients) was observed only
      in arm B. Seventeen patients responded: 11/34 (32%; 95% C.I. = 17-50%) in arm A,
      and 6/32 (19%; 95% C.I. = 7-36%) in arm B. Median survival times of 40 and 34
      weeks, respectively, were reported in arm A and B. Stage IIIB and squamous cell
      histology were associated with a higher probability of response. In conclusion,
      the partial replacement of CDDP with CBDCA in combination with VP16 slightly
      improves the tolerance of the treatment in terms of nephro- and neurotoxicity;
      however, it induces a significant increase in hematologic toxicity. In view of
      this unfavourable toxicologic profile and of the discouraging response rate
      observed, this regimen cannot be recommended as standard treatment in advanced
      NSCLC.

PMID- 8865130
TI  - Alpha-fetoprotein-producing adenocarcinoma of the lung.
AB  - We herein present a case of metachronous primary lung cancers, the first of which
      was adenosquamous cell carcinoma and the second of which was poorly
      differentiated adenocarcinoma. At the time the second lung cancer was detected 5
      years after being operated on for the first cancer, a high level of serum alpha
      fetoprotein (AFP) was noticed, but no elevation of other tumor markers was
      observed. In addition, no liver metastases, chronic liver diseases or other
      systemic abnormalities were seen either. The serum AFP level was 696 ng/ml, and
      the profile of lectin affinity showed a tumor-derived pattern. Two weeks after
      the operation, the serum AFP level decreased to a normal level. An
      immunohistochemical analysis confirmed that the exact origin of AFP was the tumor
      tissue. A specimen taken from the first lung cancer was not stained by the same
      procedures, which thus indicated this case to be a double primary lung cancer.

PMID- 8865129
TI  - Paclitaxel plus hydroxyurea as second line therapy for non-small cell lung
      cancer.
AB  - We tested paclitaxel (Taxol) and low dose hydroxyurea as second line therapy in
      30 patients with non-small cell lung cancer since both drugs are active against
      non-small cell lung cancer in other settings, and since hydroxyurea may reverse
      chemotherapy resistance by disrupting double minute chromosomes. Hydroxyurea 500
      mg was given orally each Monday, Wednesday, Friday starting 1 week before
      paclitaxel, and continuing until removal from study. Paclitaxel 135 mg/m2 was
      given i.v. over > or = 1 h every 3 weeks with dexamethasone, diphenhydramine, and
      ranitidine. Patients could have paclitaxel doses escalated to 175 mg/m2 in course
      2 and to 200 mg/m2 in course 3, where tolerated. Sixteen males and 14 females
      were treated. All patients had previously received a single cisplatin-based
      chemotherapy regimen and 23 had previously received radiotherapy. Twelve patients
      had adenocarcinomas, six had squamous cell carcinomas, and 12 had large cell
      carcinomas. Eight patients had Stage IIIb cancers and 22 had Stage IV. Paclitaxel
      doses were 135 mg/m2 in 56 courses, 175 mg/m2 in 24, and 200 mg/m2 in 15.
      Treatment was well tolerated. Median granulocyte nadirs were 2.5 (x 10(9)/l) for
      paclitaxel 135 mg/m2, 1.8 for 175 mg/m2, and 1.3 for 200 mg/m2. No patient
      developed febrile neutropenia, and none required a dose reduction. Two patients
      had reversible anaphylaxis. Other toxicities were quite tolerable. They included
      fatigue, myalgias, dizziness, paresthesias, diarrhea, alopecia, mucositis,
      flushing, headache, swollen red hands, and anxiety. One patient had a partial
      remission and 15 had stable disease (including six with minor responses). Median
      survival was 20 (95% CI, 12-34) weeks, with 19% of patients remaining alive at 1
      year from initiation of treatment. This is a well-tolerated regimen with modest
      activity as second line chemotherapy for patients with non-small cell lung cancer
      previously treated with cisplatin regimens. Higher doses would be feasible and
      other strategies are now being explored.

PMID- 8865131
TI  - Actinomycosis, a sheep in wolves' clothes.
AB  - We present a patient referred for radiotherapy for a presumed pulmonary
      malignancy, who was found to suffer from an actinomycotic infection. This case
      illustrates the importance of early consideration of actinomycosis when
      diagnostic methods are negative for malignancy or specific chestwall and bony
      lesions are observed.

PMID- 8865132
TI  - Mechanisms of action of sex steroid hormones: basic concepts and clinical
      correlations.
AB  - The review deals with the clinically important aspects of the basic mechanisms of
      sex steroid hormones. Steroids can act through two basic mechanisms: genomic and
      non-genomic. The classical genomic action is mediated by specific intracellular
      receptors, whereas the primary target for the non-genomic one is the cell
      membrane. Many clinical symptoms seem to be mediated through the non-genomic
      route. Furthermore, membrane effects of steroid and other factors can interfere
      with the intranuclear receptor system inducing or repressing steroid-and receptor
      specific genomic effects. These signalling pathways may lead to unexpected
      hormonal or anti-hormonal effects in patients treated with certain drugs. Steroid
      receptors (SRs) are members of a large family of nuclear transcription factors
      that regulate gene expression by binding to their cognate steroid ligands, to the
      specific enhancer sequences of DNA (steroid response elements) and to the basic
      transcription machinery. SRs are phosphoproteins, which are further
      phosphorylated after ligand binding. The role of phosphorylation in receptor
      transaction is complex and may not be uniform to all SRs. However,
      phosphorylation/dephosphorylation is believed to be a key event regulating the
      transcriptional activity of steroid receptors. SR activities can be affected by
      the amount of SR in the cell nuclei, which is modified by the rate of
      transcription and translation of the SR gene as well as by proteolysis of the SR
      protein. There is an auto- and heteroregulation of receptor levels. Some of the
      SRs appear to bind specific protease inhibitors and exhibit protease activity.
      The physiological significance of this weak proteolytic activity is not clear.
      Some SRs are expressed as two or more isoforms, which may have different effects
      on transcription. Receptor isoforms are different translation or transcription
      products of a single gene. Isoform A of the progesterone receptor is a truncated
      form of PR isoform B originating from the same gene, but it is able to suppress
      not only the gene enhancing activity of PR-B but also that of other steroid
      receptors. From the clinical point of view, it is important to note that the
      final hormonal effect in a target tissue is dependent on the cross talk between
      different nuclear steroid receptors and on expression of receptor isoforms.

PMID- 8865133
TI  - Progestins.
AB  - The history of progesterone and hormone replacement therapy goes back to 1934
      when Butenandt obtained crystalline progesterone and Kaufmann started to treat
      ovariectomized women with both estrogens and progesterone (Table 1). Today
      synthetic perorally active 19-nortestosterone and 17-alpha-hydroxyprogesterone
      derivatives are used in addition to contraception and hormone replacement therapy
      in a variety of gynecological disorders. In hormone replacement therapy progestin
      is added only to prevent development of hyperplasia of the endometrium and its
      consequences. However, because progestins may cause both subjective and metabolic
      adverse effects minimum effective antiproliferative doses are recommended. The
      duration of the progestin phase cannot be shortened to less than 10 days whereas
      the frequency of administration apparently can be reduced without increased risk
      of hyperplasia. Development of new modes of administration may further help in
      reduction of the doses.

PMID- 8865134
TI  - Gonadotropins and ovarian gonadotropin receptors during the perimenopausal
      transition period.
AB  - As an early sign of perimenopause, the menstrual cycles become irregular.
      Associated with this irregularity, serum gonadotropin levels increase. There are
      studies correlating these changes to ovarian follicular morphology and number,
      but no reports are available, to our knowledge, correlating the increases in
      gonadotropin levels to respective cellular receptors. In fact, the regulation of
      gonadotropin receptors is poorly understood in the human. The action of
      gonadotropins on gonadal function is mediated through specific binding of the
      hormones to receptors located on the surface of target cells followed by
      activation of intracellular second messenger systems. In the ovary, the target
      cells for FSH are granulosa cells of ovarian follicles, while the action of LH is
      mediated through binding of the ligand to theca, granulosa and luteal cells. The
      cell-surface receptors for gonadotropins are located respectively on these cell
      types. The molecular nature of FSH receptors and LH receptors has been
      characterized in many species, and their structure is well-known both on the
      protein and nucleic acid level. Despite the vast amount of studies in rodents,
      there is limited information available on the regulation of gonadotropin
      receptors in the human. In a recent study, serum LH and FSH levels were
      correlated to respective receptor levels in ovarian tissue in order to better
      understand gonadotropin action and the physiology of the menopause in the human.
      High serum gonadotropin levels in perimenopause suggested the existence of low
      ovarian gonadotropin receptor levels. In most patients who are still experiencing
      cyclic menstrual bleeding no FSH receptors were detected possibly due to severe
      disturbances in follicular FSH receptor synthesis prior to ovarian follicle
      exhaustion.

PMID- 8865135
TI  - Hormonal regulation of the normal breast.
AB  - The breast is a target organ for reproductive hormones but basic knowledge on
      hormonal effects is very poor. Available data indicate that the breast is
      regulated in a specific manner which is distinct from the endometrium and other
      target organs. It seems clear that the breast undergoes cyclic changes during the
      menstrual cycle and that in vivo there is a direct stimulatory action of
      progestogens on the breast. In surgically postmenopausal female macaques
      continuous combined estrogen/progestogen therapy was found to induce greater
      proliferation than estrogen alone.

PMID- 8865136
TI  - Female menopause, hormone replacement therapy, and cognitive processes.
AB  - OBJECTIVES: To give definitions of and to describe the research techniques for
      cognitive functions. Further, to describe the effect of female aging and hormone
      replacement therapy on cognitive functions. METHODS: Literature search of
      pertinent publications and description of initial steps of own research projects.
      CONCLUSIONS: Effect of aging and hormone replacement therapy on cognitive
      functions has been researched very insufficiently, and with conflicting
      conclusions. The best available information suggests that hormone replacement
      therapy might bring about considerable benefit in this regard, and be of
      advantage even in trying to prevent senile dementia.

PMID- 8865137
TI  - Hormone replacement therapy: clinical benefits and side-effects.
AB  - Beside well-established clinical benefits, the current doses of oestrogens may
      induce clinical side-effects leading to non-compliance and loss of efficacy.
      During a normal menstrual cycle the incidence of any cyclic discomfort is
      consistently reported to be lowest during the mild-follicular phase when plasma
      E2 remains between 60 and 150 pg/ml. The incidence of pregnancy-like symptoms
      such as bloating, breast tenderness and mood swings tends to increase in mid
      luteal phase when E2 increases upto 150 pg/ml. On the other hand incidence of
      asthenia, sleep disturbances, depressive mood, headaches and migraines increase
      during perimenstrual days when E2 drops to 40 pg/ml or below. Accordingly
      experimental and human studies in castrated animals and postmenopausal women
      suggest that plasma E2 around 100 pg/ml is optimal for treatment of hot flushes,
      prevention of bone loss and cardiovascular protection. Due to large
      interindividual variation in estrogen clearance rate, it is unlikely that any
      standardized unique dose of oral or non-oral formulations will reproduce the
      optimal levels in all postmenopausal users. Efforts for individual titration are
      mandatory to improve compliance and actual efficacy on a long term. Because older
      postmenopausal women tend to have a better clinical tolerance to low E2 levels,
      objective markers of efficacy should also be identified when the aim of HRT is
      the prevention of osteoporosis or vascular diseases. In addition clinical and
      metabolic side-effects related to added progestins can be substantially reduced
      by the use of lower dose inducing amenorrhea and by progesterone instead of
      synthetic steroids.

PMID- 8865138
TI  - Cancer risk in women receiving estrogen-progestin replacement therapy.
AB  - OBJECTIVES AND METHODS: The epidemiological literature was reviewed in order to
      evaluate the relationship between hormone replacement therapy and risk of cancer
      in the breast and reproductive organs. RESULTS: For breast cancer, there is no
      evidence of an overall increase in the risk. According to several studies, but
      not all, the duration of intake seems to affect the risk. Many years of intake of
      both estradiol compounds and conjugated estrogens can be assumed to increase the
      risk of breast cancer 1.5-2-fold. The addition of progestins does not seem to
      alter (reduce) the duration-risk relationship. The magnitude of risk increase is
      likely to be small and may be explained partly by methodological problems, or by
      differences in study populations. The prognosis in patients with HRT-related
      breast cancer seems to be more favourable than for non-exposed breast cancer
      patients. Because of the importance of the issue, and inconsistencies in results,
      further research is urgent. Especially, there is an urgent need to define sub
      groups of women who would be susceptible to an adverse influence of HRT.
      Regarding endometrial cancer, a duration-dependent strong risk relationship with
      long-term intake of estrogens only is established. The level of risk increase is
      about 10-fold after 10 or more years of intake, a risk relationship that seems to
      decrease after discontinuation of treatment. Added progestins for at least 10
      days per cycle can reduce or eliminate the risk increase. Tumors occurring after
      estrogen replacement have favourable biological characteristics. Future research
      will be needed to define the long-term safety of various progestin regimens.
      Ovarian cancer risk does not seem to be affected by HRT. Available data are
      inconsistent and contradictory. Due to the pronounced protective effect of oral
      contraceptives, further research is needed to measure effects of estrogen
      progestin combined regimens. Cervical cancer risk has not been shown to be
      affected by HRT. CONCLUSIONS: It is concluded that hormone replacement therapy,
      with estrogens alone or estrogens combined with progestins, may have important
      effects on the risk of cancer, particularly in the breast and endometrium.
      Therefore, when making a risk-benefit assessment of long-term HRT, possible risk
      relationships should be considered.

PMID- 8865139
TI  - Pathogenesis of atherosclerosis.
AB  - Atherosclerosis is a disease which affects large and medium-sized arteries.
      Typical features of atherosclerosis are accumulation of intra- and extracellular
      lipids, foam cell formation, proliferation of smooth muscle cells and
      accumulation of connective tissue. Plasma lipids and lipoproteins play an
      important role in the formation of atherosclerotic lesions. Recent evidence
      suggests that oxidation of low-density lipoprotein (LDL) may play an important
      role in the pathogenesis of atherosclerosis. Incidence of cardiovascular disease
      increase significantly after menopause. Part of the increase is due to
      atherogenic changes in plasma lipoproteins, i.e. increase in LDL and decrease in
      high density lipoprotein (HDL). Clinical endpoints of cardiovascular diseases are
      usually caused by atherosclerosis and thrombosis, both of which can be influenced
      after menopause by sex steroids. Hormone replacement therapy has anti-atherogenic
      effects on plasma lipoprotein fractions. Recent evidence also suggests that
      estrogens may have several protective effects on the vascular wall, including
      direct inhibition of LDL degradation, oxidation and smooth muscle cell
      proliferation.

PMID- 8865140
TI  - Estrogens, progestins and lipid metabolism.
AB  - OBJECTIVES: To review some aspects in the recent literature related to the
      effects of postmenopausal estrogen and progestin use on major plasma lipoprotein
      risk factors for coronary heart disease (CHD). METHODS: Collection of relevant
      information from medical journals, and by the use of Medline and Current
      Contents. RESULTS: The beneficial effects of estrogen (LDL cholesterol reduction
      and HDL cholesterol elevation) are well established. The effects on HDL are
      modified to different degrees by progestins, depending on the androgenic
      properties of the latter: the 'sex steroid sensitive' HDL2 subfraction is
      decreased by nortestosterone derived progestins with androgenic activity.
      Recently developed methodology employing stable isotopes has helped to clarify
      underlying mechanisms. Progestins alone, as well as estrogen-progestin
      combinations have been shown to reduce the plasma levels of Lp(a), another
      lipoprotein risk factor for CHD. According to one study, estrogen administered
      alone had a similar effect. CONCLUSIONS: The effects of hormone replacement
      therapies on lipid metabolism have been partly established and investigations on
      the underlying mechanisms are being published. This information will be useful
      for developing new replacement regimens with more protection against CHD and less
      adverse effects.

PMID- 8865141
TI  - Monocyte-platelet function and protection against cardiovascular disease.
AB  - Observational studies reveal a cardioprotective effect of hormone replacement
      therapy. The precise mechanisms whereby this treatment influences disease risk
      are not fully understood. Much attention has been paid to changes in lipid and
      lipoprotein metabolism, but this explains only part of the protective effect. In
      this short review, the roles of monocyte and platelet function in atherogenesis
      and thrombus formation are discussed. It is shown that hormone replacement
      therapy favourably down-regulates monocyte and platelet reactivity, which may be
      important in explaining the beneficial effect on the risk of cardiovascular
      disease.

PMID- 8865142
TI  - Estrogen-progestin replacement therapy and atherosclerosis.

PMID- 8865143
TI  - Estrogen and bone metabolism.
AB  - Estrogen plays an important role in the growth and maturation of bone as well as
      in the regulation of bone turnover in adult bone. During bone growth estrogen is
      needed for proper closure of epiphyseal growth plates both in females and in
      males. Also in young skeleton estrogen deficiency leads to increased osteoclast
      formation and enhanced bone resorption. In menopause estrogen deficiency induces
      cancellous as well as cortical bone loss. Highly increased bone resorption in
      cancellous bone leads to general bone loss and destruction of local architecture
      because of penetrative resorption and microfractures. In cortical bone the first
      response of estrogen withdrawal is enhanced endocortical resorption. Later, also
      intracortical porosity increases. These lead to decreased bone mass, disturbed
      architecture and reduced bone strength. At cellular level in bone estrogen
      inhibits differentiation of osteoclasts thus decreasing their number and reducing
      the amount of active remodeling units. This effect is probably mediated through
      some cytokines, IL-1 and IL-6 being strongest candidates. Estrogen regulates the
      expression of IL-6 in bone marrow cells by a so far unknown mechanism. It is
      still uncertain if the effects of estrogen on osteoblasts is direct or is due to
      coupling phenomenon between bone formation to resorption.

PMID- 8865144
TI  - Hormone replacement therapy and osteoporosis.
AB  - Restoration of the osteoporotic skeleton is difficult. Factors that may aggravate
      the bone loss or increase the risk of fractures should be eliminated. The
      physician may then decide whether the patient is a candidate for one of the
      treatments which either stop further bone loss or increase the bone mass. The
      decision should be based on a variety of factors and be taken together with the
      patient.

PMID- 8865145
TI  - Vitamin D treatment and bone mineral density in the aged.
AB  - The purpose of this study was to investigate whether long-term vitamin D
      treatment increased bone mineral density in the aged. The bone mineral density in
      the distal forearm and femoral neck did not differ between nine residents (mean
      age 81.0 years) of an old peoples' home who had received an annual injection of
      150,000 IU ergocalciferol during the foregoing 2-7 years (mean 5.1 years) and
      nine age-, weight- and height-matched control subjects who had subnormal 25
      hydroxyvitamin D level. The alkaline phosphatase and parathyroid hormone levels
      were clearly higher when the 25 hydroxyvitamin D level was below 10 nmol/1. The
      authors suggest that the ability of vitamin D treatment to diminish fracture
      incidence may derive from improved bone quality, not measurable by the standard
      dual energy X-ray absorptiometry, and/or improved nervous and muscular control of
      movements to counter the tendency to fall.

PMID- 8865146
TI  - Clodronate and osteoporosis.
AB  - Bisphosphonates are widely used in disorders associated with increased resorption
      of bone, particularly in Paget's disease of bone and the hypercalcaemia of
      malignancy. Their undoubted efficacy and relatively low toxicity makes them
      attractive candidates for the management of osteoporosis. The three
      bisphosphonates widely tested are etidronate, pamidronate and clodronate. Whereas
      pamidronate can only be given by intravenous infusion, clodronate may be given
      intravenously or by mouth. Unlike etidronate, even high doses of clodronate do
      not impair the mineralisation of bone, making it suitable for long-term use in
      osteoporosis. Clodronate has been shown to inhibit experimentally induced
      increases in bone resorption and in patients prevents bone loss at the menopause
      and during immobilisation. Short-term and long-term studies indicate that
      clodronate appears to stop bone loss at the lumbar spine in patients with
      vertebral osteoporosis. Long-term studies of the effects at the hip are not yet
      reported. The effects of clodronate on the frequency of osteoporotic fractures
      are not yet known and will demand well controlled long-term prospective studies.

PMID- 8865147
TI  - Individual hormone replacement therapy.
AB  - Although hormone replacement therapy is widely used in western countries,
      compliance is not very good; only a minor proportion of women starting the
      treatment continue it for over 5 years. However, long-term treatment is essential
      for primary prevention of cardiovascular diseases and osteoporosis. One reason
      for low compliance is that treatment is not planned individually. After using a
      fixed estradiol dose, serum levels of estradiol show 10-fold differences between
      subjects, independently of the routes of administration. This article briefly
      summarizes the possibility of using tailored treatment and thus improving long
      term compliance with HRT.

PMID- 8865148
TI  - Recent advances in the generation of small-molecule combinatorial libraries:
      encoded split synthesis and solid-phase synthetic methodology.

PMID- 8865149
TI  - Cellular and molecular mechanisms involved in the regulation of eosinophil
      trafficking in vivo.
AB  - The recruitment of eosinophils to sites of allergic inflammation is a complex
      process that is primarily regulated by inflammatory cytokines and chemokines.
      These molecules act in concert to stimulate peripheral eosinophilia, regulate
      homing of eosinophils to the inflammed organ, and promote eosinophil-vascular
      endothelium interactions, extravasation, chemotaxis, and localization to the site
      of the inflammatory stimulus. The essential and specific role of IL-5 in
      regulating blood and tissue eosinophilia, and the subsequent involvement of this
      leukocyte in the induction of lung damage and airway dysfunction identifies IL-5
      as a primary therapeutic target. Developing strategies to inhibit IL-5 production
      and action, such as by the delivery of inhibitory cytokines to the lung, which
      specifically down-regulate CD4+ TH2 cell responses and eosinophilic inflammation,
      may be more beneficial than the current drugs of choice for preventive treatment
      and in the relief of acute and chronic asthma and allergic disease.

PMID- 8865150
TI  - Fluoroquinolone antibacterials: SAR mechanism of action, resistance, and clinical
      aspects.

PMID- 8865151
TI  - Prion biology and diseases--laughing cannibals, mad cows, and scientific heresy.

PMID- 8865152
TI  - Effect of macrolide antibiotics on macrophage functions.
AB  - Macrolide antibiotics have a variety of actions other than antimicrobial
      activities. Recently, it has been suggested that macrolide antibiotics act as
      immunomodulators. In this study, we evaluated the effects of macrolide
      antibiotics on macrophage functions. For the macrophage, we used the mouse
      macrophage cell line J774.1. The following effects of macrolide antibiotics on
      macrophage functions were evaluated: the effect of macrolide antibiotics on
      macrophage growth; the phagocytosis of beads; cytocidal activity against Candida
      albicans; and chemotaxis to lipopolysaccharide (LPS). Macrolide antibiotics
      except for azithromycin significantly stimulated the growth of the macrophage. In
      addition, pretreatment with macrolide antibiotics except for roxithromycin
      significantly stimulated the macrophage phagocytosis of beads, macrophage
      chemotaxis to LPS, and macrophage cytocidal activity against Candida albicans.
      These results suggest that macrolide antibiotics stimulate macrophage functions.

PMID- 8865153
TI  - Hepatitis B virus with X gene mutation is associated with the majority of
      serologically "silent" non-b, non-c chronic hepatitis.
AB  - Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of
      chronic hepatitis without serological markers of known hepatitis viruses. The aim
      of this study was to reconfirm whether the HBV with the X gene mutation is
      associated with these serologically "silent" non-B, non-C (NBNC) chronic
      hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA
      was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis
      in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was
      identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase
      chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA.
      Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide
      deletion mutation at the distal part of the X region. This mutation affected the
      core promoter and the enhancer II sequence of HBV DNA and created a translational
      stop codon which truncated the X protein by 20 amino acids from the C-terminal
      end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in
      disruption of HBe antigen synthesis. These results indicate that HBV mutants are
      closely associated with the majority of serologically "silent" NBNC chronic
      hepatitis cases and the population of such mutant HBV DNAs is not uniform.

PMID- 8865154
TI  - Failure to reject an allografted tumor after elimination of macrophages in mice.
AB  - After an i.p. transplantation of an allogeneic tumor (Meth A) to C57BL/6 mice, a
      macrophage (M phi)-rich, non-T, non-NK cell population is induced as the major
      infiltrate and cytotoxic cells. We here evaluated the role of the M phi s in the
      rejection of allografted Meth A cells and characterized the M phi s in comparison
      with other well-known M phi s. At all time intervals after transplantation, the
      highest cytotoxic activities against Meth A tumor were obtained with the M phi
      rich population. In addition, the lymphocyte-rich population had a significant
      but low cytotoxic activity, whereas two other population types, granulocytes and
      large granular cells, were inactive. When the M phi-rich or the T cell-depleted M
      phi-rich population was i.p. transplanted simultaneously with Meth A cells into
      untreated C57BL/6 mice, the tumor cells were rejected without growth. After
      specific elimination of M phi s by in vivo application of dichloromethylene
      diphosphonate-containing liposomes, the cytotoxic activity against Meth A cells
      was hardly induced at the transplantation site of Meth A cells and the
      allografted Meth A tumor continued to grow, indicating that a type of M phi is
      the effector cell essential for the rejection. In contrast to other well-known M
      phi s, the cytotoxic activity against Meth A cells was cell-to-cell contact
      dependent and soluble factor (e.g., NO and TNF-alpha) independent. Moreover, the
      cytotoxic activity of the M phi s (H-2b) against 51Cr-labeled Meth A (H-2d) cells
      was inhibited by the addition of unlabeled H-2d, but not H-2b, H-2k or H-2h,
      lymphoblasts as well as Meth A cells, implying the specific interaction of the M
      phi s with H-2d cells.

PMID- 8865155
TI  - Seroprevalence of Helicobacter pylori infection in patients with connective
      tissue diseases.
AB  - To assess the possibility that Helicobacter pylori might be an etiologic agent,
      titers of anti-H. pylori IgG in sera of patients with connective tissue diseases
      [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyositis or
      dermatomyositis (PM/DM), progressive systemic sclerosis (PSS), mixed connective
      tissue disease (MCTD) and Sjogren's syndrome (SjS)] were compared with those of
      non-patient (healthy) volunteers and of patients with chronic pulmonary diseases
      (CPD) by ELISA using an extract of sonicated H. pylori as the antigen. Among
      patients with connective tissue diseases, those with SLE and RA had anti-H.
      pylori titers as low as healthy volunteers. Patients with SjS had much higher
      average titers than patients with CPD (P < 0.05). We previously reported that
      levels of myeloid calcium-binding protein (MRP8 and MRP14) were elevated in the
      serum of patients with connective tissue diseases. No correlation was found
      between serum levels of anti-H. pylori IgG and of MRP, a novel marker of
      inflammation. Furthermore, sera with high IgG titers were selected, and their
      reactivity with the H. pylori antigen were analyzed by Western blotting. H.
      pylori antigens with a variety of molecular masses were immunostained with sera
      from patients and from healthy volunteers, but a 16-kDa antigen was only
      immunostained by reaction with the sera of patients with MCTD and SjS, although
      the number of test samples was small.

PMID- 8865156
TI  - Cytokine-independent proliferation of IL-2-nonproducing CTL clones in association
      with high TCR-signal transduction responses.
AB  - Alloreactive CTL clone D2-23 proliferated in response to antigenic cells without
      IL-2 production. Among subclones of D2-23, the F1 but not F2 clone proliferated
      in response to soluble aCD3 or PMA, although both clones proliferated in response
      to immobilized aCD3, antigenic cells or soluble aCD3 plus costimulatory cells.
      The difference in responsiveness between F1 and F2 was not caused by distinct
      expression of CD3 or Fe receptors. Cyclosporin A, which totally blocks IL-2
      production of Th1 cells, barely or only partially inhibited PMA- or aCD3-induced
      proliferation of F1. F1 did not produce cytokines for proliferation of F2 in
      response to soluble aCD3. Tyrosine phosphorylation developed for various proteins
      of F1 and F2 at the levels apparently correlated to the extent of cell
      proliferation when the cells were stimulated with soluble aCD3 or PMA. The
      proliferative responsiveness of F1 and F2 to the described stimulators was
      maintained by stimulation with IL-2 plus antigenic cells, or even IL-2 alone, but
      was decreased during resting culture or by stimulation with immobilized aCD3.
      These results show evidence of a new TCR-linked mechanism for CTL proliferation
      that is independent of costimulatory cell- or cytokine-mediated signaling, but is
      originally prepared by prior stimulation with IL-2.

PMID- 8865157
TI  - Long-term acceptance of major histocompatibility complex-mismatched cardiac
      allograft induced by a low dose of CTLA4IgM plus FK506.
AB  - The immunosuppressant FK506 prolongs allograft survival. However, at therapeutic
      doses it has significant side effects. A fusion protein consisting of the
      extracellular portion of CTLA4 and the Fc portion of human IgG (CTLA4IgG) also
      prolongs allograft survival, but large doses of CTLA4IgG are required for the
      induction of cardiac allograft acceptance. Therefore, we constructed a pentameric
      form of a new CTLA4 fusion protein, CTLA4IgM. We tested whether low doses of
      CTLA4IgG or CTLA4IgM in combination with subtherapeutic doses of FK506 can
      prolong allograft survival in a synergistic fashion. C57BL/6 (H-2b) neonatal
      hearts were transplanted to CBA/J (H-2b) mice in a heterotopic, nonvascularized
      cardiac allograft model. The findings demonstrate that a combination of low doses
      of FK506 plus a pentameric form of CTLA4Ig, CTLA4IgM, leads to significant graft
      survival, while a combination of FK506 plus CTLA4IgG does not.

PMID- 8865158
TI  - Adherence of peripheral blood leukocytes to cytomegalovirus-infected fibroblasts.
AB  - Peripheral blood monocytes and B cells adhered to cytomegalovirus (CMV)-infected
      fibroblasts, whereas T cells and polymorphonuclear leukocytes did not adhere to
      either CMV-infected or uninfected fibroblasts. When T cells were activated with
      anti-CD3 antibody, activated T cells demonstrated adherence and cytotoxicity to
      both CMV-infected and uninfected fibroblasts. Adherence of peripheral blood
      mononuclear cells (PBMC) and cytotoxicity mediated by adherent activated T cells
      were blocked by treatment of CMV-infected fibroblasts with anti-ICAM-1 antibody
      and by treatment of leukocytes with anti-LFA-1 antibody. These data suggest that
      an interaction of ICAM-1 and LFA-1 is responsible for the adherence of leukocytes
      and for adherent activated T cell-mediated cytotoxicity against CMV-infected
      fibroblasts.

PMID- 8865159
TI  - Genotype analysis of hepatitis C virus among blood donors and inmates in Metro
      Manila, The Philippines.
AB  - Antibodies against hepatitis C virus (HCV) were detected in 18 (2.3%) of 800 sera
      from commercial blood donors and 23 (4.6%) of 502 sera from inmates in Metro
      Manila, the Philippines. The difference in the antibody prevalence between the
      two groups was statistically significant (P < 0.05). HCV RNA was detected in 14
      (78%) of the 18 antibody-positive sera from blood donors and 19 (83%) of the 23
      antibody-positive sera from inmates. Genotype analysis revealed that HCV-2a (7%).
      Among inmates, on the other hand, HCV-1a (68%) was most common, followed by HCV
      1b (11%), HCV-2a (5%) and HCV-2b (5%). Overall, HCV-1a and HCV-1b appeared to be
      predominant among them. Thus, the genotype prevalence in the Philippines was
      distinct from those in other Southeast Asian countries such as Thailand, Vietnam
      and Indonesia, and also distinct from those in the Far East including Taiwan,
      Mainland China and Japan.

PMID- 8865160
TI  - Differential regulation of inhibin/activin alpha- and beta A-subunit and
      follistin mRNAs by cyclic AMP and phorbol ester in cultured human granulosa
      luteal cells.
AB  - Granulosa cell-derived inhibin A (a dimer of alpha- and beta A-subunits), activin
      A (a homodimer of beta A-subunits) and the activin-binding protein follistatin
      are important regulators of human ovarian steroidogenesis. We here studied how 8
      bromo-cAMP (8br-cAMP), a protein kinase A activator, and 12-O
      tetradecanoylphorbol 13-acetate (TPA), a protein kinase C activator, affect the
      steady-state levels of alpha- and beta A-subunit and follistatin mRNAs in
      cultured human granulosa-luteal cells. 8br-cAMP induced alpha- and beta A-subunit
      and follistatin steady-state mRNA levels in a time- and concentration-dependent
      manner. The levels of alpha-subunit mRNAs were stimulated by 8br-cAMP in a
      sustained manner with a maximal induction seen at the time points 24 and 48 h. By
      contrast, beta A-subunit and follistatin mRNA levels were rapidly and transiently
      induced by 8br-cAMP with maximal effects observed at 3 h and 8 h, respectively.
      TPA did not affect basal alpha-subunit mRNA levels but it rapidly induced beta A
      subunit mRNAs at 3 h and the stimulation was still evident at 48 h. TPA induced
      follistatin mRNA levels with kinetics similar to 8br-cAMP but to a lesser extent.
      Moreover, 8br-cAMP and TPA stimulated beta A-subunit and follistatin mRNA levels
      synergistically at 3 h. By contrast, TPA had a potent inhibitory effect on 8br
      cAMP- and hCG-induced alpha-subunit levels. Neither 8br-cAMP nor TPA regulated
      inhibin/activin beta B-subunit mRNA levels. Taken together the activation of
      protein kinase-A and -C by 8br-cAMP and TPA, respectively, lead to clearly
      differential responses in the steady-state levels of inhibin activin alpha- and
      beta A-subunit and follistatin mRNAs. These results suggest that the inhibin A
      vs. activin A ratio as well as follistatin levels are regulated by multiple
      second-messenger pathways in the human ovary.

PMID- 8865161
TI  - Interleukin-4 and interleukin-13 inhibit estrogen-induced breast cancer cell
      proliferation and stimulate GCDFP-15 expression in human breast cancer cells.
AB  - Human breast carcinomas are frequently infiltrated by inflammatory cells
      secreting several cytokines which may regulate the activity of both immune cells
      and neoplastic cells. The present study was designed to examine the potential
      action of interleukin-4 (IL-4) and interleukin-13 (IL-13) in human breast cancer
      cells. Exposure of ZR-75-1 breast cancer cells to IL-4 or IL-13 for 10 days
      decreased the amplitude of the mitogenic action of 17 beta-estradiol by 75% and
      55%, respectively, while these cytokines failed to change basal cell
      proliferation. These cytokines also exerted a similar action in T-47D cells.
      Exposure to IL-4 or IL-13 markedly increased gross cystic disease fluid protein
      15 (GCDFP-15) release in both ZR-75-1 and T-47D cells. The half-maximal
      stimulatory effects of IL-4 and IL-13 on GCDFP-15 secretion were exerted at
      respective values of 16 +/- 3 pM and 91 +/- 8 pM in T-47D cells incubated for a
      period of 10 days. The effect of IL-13 was not additive to that elicited by IL-4,
      whereas the stimulation of GCDFP-15 release by these interleukins were additive
      to that exerted by maximally effective concentrations of the androgen
      dihydrotestosterone and the synthetic glucocorticoid dexamethasone. Furthermore,
      exposure of ZR-75-1 cells of IL-4 and IL-13 increased GCDFP-15 mRNA levels by 5.5
      and 6.0-fold, respectively. The present results demonstrate that IL-4 and IL-13
      may decrease estrogen-induced breast cancer cell proliferation and induce the
      expression of a breast cancer marker, thus strongly suggesting that breast cancer
      cells are targets of both IL-4 and IL-13 action.

PMID- 8865162
TI  - Multiple stat complexes interact at the interferon regulatory factor-1 interferon
      gamma activation sequence in prolactin-stimulated Nb2 T cells.
AB  - Interferon regulatory factor-1 (IRF-1) is a major immediate early gene induced by
      prolactin (PRL) in a biphasic, cell cycle-dependent manner in Nb2 T cells. This
      biphasic expression (30 min and 10 h) is mediated in part by an interferon-gamma
      activation sequence (GAS) in the IRF-1 promoter which binds factors belonging to
      the Signal Transducers and Activators of Transcription (Stat) family. By
      electrophoretic mobility shift assays (EMSA), Stat1 alpha was found to be the
      major and Stat5a a minor component of the 30 min complex. At 10 h, Stat-like
      factors were again found at the IRF-1 GAS. Western blot analyses show that Stat5a
      was rapidly induced by PRL to enter the nucleus, but unexpectedly, Stat1 alpha
      and the alternatively-spliced Stat1 beta were already present in the uninduced
      nucleus. Further, Stat1 alpha but not Stat1 beta is preferentially tyrosine
      phosphorylated in response to PRL stimulation. Our studies suggest that multiple
      Stat complexes may contribute to the biphasic transcription of the IRF-1 gene in
      PRL-stimulated T cells.

PMID- 8865163
TI  - Insulin/IGF-1 modulation of the expression of two estrogen-induced genes in MCF-7
      cells.
AB  - Estrogen responses of human breast cancer cell lines have frequently been shown
      to be promoted by insulin. We have examined the action of insulin, and its
      interaction with estradiol, in regulating the expression of the estrogen-induced
      genes, LIV-1 and pS2. Both hormones cause increases in mRNA levels of the two
      genes but do so by distinct mechanisms. The concentration of insulin required to
      produce this effect suggests that it is acting via its ability to bind to the IGF
      1 receptor. Both insulin and estradiol exert their effects at the level of
      transcription. Induction by insulin is dependent upon continued protein synthesis
      whereas induction by estradiol is not. Induction by both insulin and estradiol is
      prevented by the pure antiestrogen. ICI 164384, indicating the requirement for an
      activatable estrogen receptor. Insulin does not stimulate LIV-1 expression via
      the androgen receptor. These results demonstrate that both estradiol and insulin
      can stimulate the transcription of these estrogen-inducible genes, by separate
      mechanisms both of which involve the estrogen receptor.

PMID- 8865164
TI  - Presence and mRNA expression of T3 receptors in differentiating rat brown
      adipocytes.
AB  - Nuclear T3 binding and T3 receptors (TR) expression were studied in brown
      adipocytes differentiated in culture from precursor cells. High affinity T3
      receptors were found. During adipocyte differentiation maximal binding capacity
      (MBC) was doubled (up to 763 fmol T3/mg DNA), and an apparent decrease in
      receptor affinity was also observed (due to a decrease in the association rate
      constant). A very high disappearance rate of T3 was found in the cellular and
      nuclear fractions under binding assay conditions (serum-free medium). MBC
      increased 30% under hypothyroid conditions, but was not affected by physiological
      doses of T3 or retinoic acid. TR beta 1, TR alpha 1 and c-erbA-alpha 2 mRNAs were
      detected in brown adipocytes. During differentiation TR beta 1 decreased to 30%.
      Long exposure to T3 increased 2-fold TR beta 1 and decreased TR alpha 1 levels,
      when using insulin-depleted medium. Short exposure (4 h) to 10 nM insulin reduced
      both TR beta 1 and TR alpha mRNAs species.

PMID- 8865165
TI  - Putative intestinal estrogen receptor: evidence for regional differences.
AB  - Previously we demonstrated that 17 beta-estradiol (E2) stimulates intestinal
      calcium absorption and enhances uptake of calcium by intestinal mucosal cells in
      vitro, and that the latter contains estrogen receptor (ER)-like proteins and
      mRNAs. The current study was undertaken to further characterize the putative
      intestinal ERs using RT-PCR analysis, Western blot analysis, Southern blot
      analysis, ligand binding assays and gel shift assays. RT-PCR analysis using
      primers directed at the terminal end of the A/B domain of the uterine ER
      confirmed our previous finding that intestinal ER mRNAs are present throughout
      the intestine, with the exception that the duodenum lacked the amplified region.
      Western blot analysis, using ER-715 antibody, detected the expected 68- to 70-kDa
      ER protein and additional 58-, 46- and 41-kDa proteins in the uterus and colon,
      while duodenal extract contained only a faint 46-kDa and strong 28-kDa protein
      bands. Southern blot analysis performed on enzyme-digested genomic DNAs
      demonstrated the presence of ER-like sequences in genomic DNA from the uterus,
      duodenum and colon. However, enzyme restriction maps of genomic DNAs from
      intestinal segments were different from the map for uterine genomic DNA digested
      with similar enzymes. In ligand binding assays, 125I-labeled E2 bound
      specifically to 46-kDa protein in duodenal, colonic and uterine extracts and the
      binding was competitively inhibited by excess cold E2. Gel mobility shift assays
      using 32P-labeled vitellogenin derived ERE demonstrated that jejunal, colonic and
      uterine ER protein contain the classical DNA binding domain. In addition, ERE
      bound in a specific fashion to sites in genomic DNAs from the uterus, colon and
      jejunum. In contrast, protein extracts and genomic DNAs from the duodenum failed
      to bind to 32P-labeled ERE and, consequently, appear to be devoid of the
      classical DNA binding domain. These findings establish the presence of ER-like
      proteins and genes in intestinal mucosal cells of rats and suggest that the
      duodenum contains a variant ER gene that encodes a variant ER protein.

PMID- 8865166
TI  - Cycloheximide enhances ACTH-receptor mRNA through transcriptional and post
      transcriptional mechanisms in bovine adrenocortical cells.
AB  - We have previously shown that ACTH is one of the few polypeptide hormones having
      a positive trophic effect, not only on the number, but also on the expression of
      its own receptors. In the present study, we investigated whether the constitutive
      and ACTH-induced expression of ACTH-receptor (ACTH-R) mRNA in bovine
      adrenocortical cells (BAC) requires new protein synthesis. The results show that
      cycloheximide alone, an inhibitor of protein synthesis, induced a time- and dose
      dependent increase in the constitutive level of the ACTH-R major transcript of
      3.6 kb in BAC. The maximal stimulation (5.17 +/- 1.15 fold, n = 4) was obtained
      after 24 h treatment with 5 micrograms/ml cycloheximide. The effect of
      cycloheximide was specific and not directly related to translational arrest since
      other protein synthesis inhibitors acting through different mechanisms, emetine
      and puromycin, were unable to reproduce such an effect at concentrations
      inhibiting protein synthesis. The effect of cycloheximide involved an increase in
      the half-life and the transcription rate of the major transcript of ACTH-R (2-
      and 8.4-fold respectively). In addition, the results also demonstrated that
      neither the constitutive nor the ACTH-induced expression of ACTH-R require new
      protein synthesis.

PMID- 8865167
TI  - Expression and regulation of G alpha q and G alpha 11 mRNAs and proteins in
      bovine adrenal cells.
AB  - Bovine adrenal cortical cells (BAC) express corticotropin (ACTH) and angiotensin
      II (AngII) receptors (AT1 subtype), which are coupled to adenylate cyclase and
      phosphoinositide pathways, respectively. The coupling of AT1 to phosphoinositide
      breakdown is mainly pertussis toxin-insensitive suggesting that this receptor is
      coupled to Gaeq/Gae11. In the present work we have demonstrated that BAC express
      G alpha q and G alpha 11 mRNA and proteins, and their variation during culture as
      well as their regulation by ACTH and AngII is different. ACTH enhanced G alpha q
      mRNA levels mainly by increasing the transcription rate. In addition, ACTH
      increased both G alpha q and G alpha 11 proteins without changing their half
      lives. In contrast, AngII reduced both G alpha q mRNA and protein and increased G
      alpha 11 mRNA but not G alpha 11 protein. The decrease of G alpha q mRNA levels
      was mainly due to a marked reduction of its half-life. These changes in G alpha
      q/G alpha 11 proteins induced by both hormones were associated with an enhanced
      AngII-induced inositol phosphate accumulation, more marked after stimulation with
      ACTH than after AngII pretreatment. In summary, the present results demonstrated
      that BAC express both G alpha q and G alpha 11 and their regulations are
      different and in contrast to other cell types these regulations do not involve
      changes in the half-life of G alpha q/G alpha 11 proteins.

PMID- 8865168
TI  - Contextual dependence of steroid receptor function on an androgen-responsive
      enhancer.
AB  - The enhancer of the mouse sex-limited protein (Slp) gene includes a consensus
      hormone response element (HRE) that interacts with several auxiliary elements for
      steroid induction. The 160-bp fragment. C' delta 2, confers response to androgen
      or glucocorticoid in transfection, while a 120-bp subfragment, C' delta 9, is
      activated only by androgen in some cells. Site-directed mutants were tested to
      identify elements affecting differential response of androgen or glucocorticoid
      receptors (AR, GR). While most mutations of C' delta 2 affected induction by
      either steroid similarly, disruptions of the consensus HRE or an octamer-like
      sequence were more severe for GR than AR activity. An HRE half-site was critical
      to androgen-specific induction of C' delta 9 but had little impact in the
      nonspecific C' delta 2 context. In DNase I footprinting, full-length AR and GR
      bound similarly to the consensus HRE but dissimilarly to nonconsensus sites.
      Intriguingly, NF-kappa B bound the region of C' delta 2 absent from C' delta 9.
      Expression of I kappa B decreased response of C' delta 2, but not C' delta 9,
      confirming a permissive role of NF-kappa B in steroid activation. In this case,
      different factors may associate with receptors in the presence of NF-kappa B than
      those that confer androgen specificity in NF-kappa B's absence, suggesting that
      exclusion of some factors from a specific transcription complex is as crucial as
      inclusion of others. This dissection of C' delta 2 and C' delta 9 in vitro
      reveals subtle distinctions in AR and GR interactions that may underlie specific
      hormonal response in vivo.

PMID- 8865169
TI  - Differential regulation of 11 beta-hydroxylase and aldosterone synthase in human
      adrenocortical H295R cells.
AB  - In humans the last steps in the synthesis of aldosterone and cortisol rely on the
      activity of two cytochrome P450 genes termed CYP11B2 (aldosterone synthase;
      P450aldo) and CYP11B1 (11 beta hydroxylase; P450cl1). The mechanisms which lead
      to differential expression of these two genes within the adrenal cortex are not
      well-defined. The human adrenocortical cell line. H295R, was utilized in this
      study to examine the intracellular second messenger pathways regulating
      expression of P450aldo and P450c11. using specific ribonuclease protection
      assays. Treatment of H295R cells with angiotensin II or potassium (K+) caused a
      time-dependent induction in the level of P450aldo transcripts. While K+ treatment
      was more specific for the induction of P450aldo mRNA, treatment with angiotensin
      II increased levels of both P450aldo and P450c11 transcripts. To define the
      second messenger systems which influence transcript levels for these enzymes, the
      effects of agonists of the protein kinase A, protein kinase C, and calcium
      pathways were tested on the expression of P450aldo and P450c11. Activation of the
      protein kinase A pathway by the agonists, dibutyryl cAMP or forskolin,
      preferentially increased the P450c11 transcript to a greater degree than
      P450aldo. Interestingly, activation of the protein kinase C pathway by
      tetradecanoylphorbol acetate (TPA) did not alter transcripts for either P450aldo
      or P450c11. The calcium channel agonist BAYK 8644 mimicked the effects of K+ by
      increasing the transcript for P450aldo. However, the calcium channel blocker
      nifedipine attenuated the stimulatory effects of angiotensin II and K+ on the
      levels of P450aldo. However, the calcium channel blocker nifedipine attenuated
      the stimulatory effects of angiotensin II and K+ on the levels of P450aldo
      transcripts without affecting the stimulatory effect of dbcAMP. This study
      demonstrates that the protein kinase A pathway preferentially induces P450c11
      mRNA over that of P450aldo. In addition, pharmacologic agents that affect calcium
      levels provide evidence for an additional regulatory mechanism in modulating the
      expression of P450aldo. This is of importance since the major physiologic
      regulators of aldosterone secretion, angiotensin II and K+ are able to increase
      intracellular calcium but have little effect on intracellular cAMP levels.

PMID- 8865170
TI  - Analysis of the promoter of the NAD+ dependent 11 beta-hydroxysteroid
      dehydrogenase (HSD11K) gene in JEG-3 human choriocarcinoma cells.
AB  - The NAD+ dependent (K or type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase
      oxidizes glucocorticoids and thus prevents them from occupying mineralocorticoid
      receptors. Mutations in the HSD11K (HSD11B2) gene encoding this isozyme cause a
      genetic form of hypertension, the syndrome of apparent mineralocorticoid excess
      (AME). This isozyme is expressed at high levels in placenta and kidney but is
      undetectable in liver. We have now analyzed the proximal 1788 nucleotides (nt) of
      the 5' flanking region of the HSD11K gene to identify transcriptional regulatory
      elements that are active in JEG-3 human choriocarcinoma cells. Using luciferase
      reporter constructs, the region from -2 to -330 nt relative to the initial ATG
      codon was identified as an essential region for basal transcription of the HSD11K
      gene. Two segments in this region, -278 to -257 and -215 to -194. were protected
      in DNase 1 footprinting analysis. Both segments have consensus binding sites for
      the Spl transcription factor. Gel shift assays of these segments show several DNA
      protein complexes using JEG-3 nuclear extract. Only the slowest migrating complex
      was competed by an antiserum to Spl. These results suggest that the two Spl
      sites, either alone or in combination, are essential for transcription of the
      HSD11K gene in JEG-3 cells.

PMID- 8865171
TI  - Iodine-induced thyroid inhibition and cell necrosis: two consequences of the same
      free-radical mediated mechanism?

PMID- 8865172
TI  - Diagnostic potential of sefA DNA probes to Salmonella enteritidis and certain
      other O-serogroup D1 Salmonella serovars.
AB  - Salmonella enteritidis thin fimbriae, SEF14, were found to be restricted to S.
      dublin and the predominantly poultry-associated members of the Salmonella O
      serogroup D1, S. enteritidis, S. berta, S. gallinarum and S. pullorum, when
      tested by Western and ELISA analysis from among 90 Salmonella isolates of 42
      serovars, as well as from members of several related genera of the
      Enterobacteriaceae. These five serovars and a single isolate of S. typhi (D1)
      were also detected by hybridization of genomic DNA from 732 Salmonella isolates
      of 117 serogroups to gene probes derived from the S. enteritidis sefA (fimbrin
      gene), sefB (chaperone) or sefC (outer membrane protein) genes encoding proteins
      involved in SEF14 biosynthesis. None of 250 Enterobacteriaceae or 27 other
      eubacterial isolates tested hybridized to the sef probes. The sefA, sefB and sefC
      genes were amplified from these six Salmonella serovars by PCR using primer pairs
      designed from sefA, sefB or sefC of S. enteritidis. DNA sequencing of sefA genes
      from these five serovars indicated limited sequence variability among sefA genes
      and recognition of individual base pairs which could potentially differentiate
      certain strains of S. enteritidis, S. dublin and S. gallinarum.

PMID- 8865173
TI  - Detection of M. tuberculosis DNA using thermophilic strand displacement
      amplification.
AB  - Strand Displacement Amplification (SDA) is an isothermal, in vitro method of
      amplifying DNA that is based upon the combined action of a DNA polymerase and
      restriction enzyme. Previously, a form of SDA was developed which utilizes the
      exonuclease deficient Klenow fragment of E. coli polymerase I (exo Klenow) and
      the restriction enzyme HincII to achieve 10(8)-fold amplification in 2 h at 37
      degrees C (Walker, G.T., 1993, PCR Methods and Applications 3; 1-6). A new
      thermophilic form of SDA is reported here which uses a restriction endonuclease
      from Bacillus stearothermophilus (BsoBI) and a 5'-->3' exonuclease deficient
      polymerase from Bacillus caldotenax (exo Bca). SDA was used to amplify DNA from
      Mycobacterium tuberculosis. An amplification factor of 10(10)-fold was achieved
      after 15 min of SDA at 60 degrees C. The new thermophilic system is much more
      specific than the previous mesophilic system as evidenced by a dramatic decrease
      in background amplification products. Thermophilic SDA was also optimized with
      dUTP substituted for TTP to enable amplicon decontamination using uracil-DNA
      glycosylase.

PMID- 8865174
TI  - Single molecule detection of RNA reporter probes by amplification with Q beta
      replicase.
AB  - The addition of target-specific probe sequences within MDV RNA, an otherwise
      efficient template for Q beta replicase, generally resulted in RNA molecules with
      inferior replication properties, including reduced replication rates and poor
      sensitivities. We have discovered that the replication characteristics of MDV RNA
      molecules with internally placed probe sequences are dramatically affected by
      short RNA sequences (spacer elements) at the 5' and 3' ends of the probe
      sequence. For a given probe sequence, the sequences of the flanking spacer
      elements effected replication sensitivity by six orders of magnitude and
      replication rate by three fold. By taking advantage of spacer elements, internal
      MDV probes were developed that permitted the reproducible, real time,
      fluorescence detection of a single RNA molecule in less than 25 min through
      amplification with Q beta replicase. RNA structural analysis of such probes
      suggested that the spacer elements functioned by allowing the RNA to fold in a
      way which substantially maintained the tertiary structure of the MDV domain. MDV
      reporter probes with suitable replication properties were obtained from libraries
      of RNA molecules in which the probe sequence was flanked by many different spacer
      elements (generated by random nucleotide synthesis). We demonstrated that this is
      a general method for developing RNA reporter molecules which are rapidly and
      reproducibly amplified by Q beta replicase, even from a single molecule.

PMID- 8865175
TI  - Identification and characterization of a generic DNA probe capable of detecting
      plasmodial infections in blood.
AB  - DNA-based detection systems are being rapidly adapted for diagnostic
      technologies. The currently available non-radioactive DNA techniques for malaria
      detection are primarily based on probes which are species-specific. The major
      requirement of a cross-species (generic) diagnostics is the identification of an
      universal probe which is long enough to be used in either PCR amplification or
      solid state capture of the hybrids, the two principal techniques currently used
      in the field of non-radioactive DNA detection. This paper describes a DNA
      sequence (pARC 178), originally obtained from P. falciparum genomic library,
      which is also present in other malarial species. Southern-blot analysis indicates
      that this sequence is derived from a repetitive DNA element. This DNA fragment
      encodes for a small RNA species of approximately 120 bases. PCR primers based on
      this sequence amplifies the expected size (157 bp) product from the genomic DNA
      isolated from P. falciparum, P. vivax, P. berghei, P. yoelii, P. vinckei and P.
      chabaudi thus confirming its generic nature. The utility of this probe is further
      demonstrated by its capability in successfully detecting P. falciparum and P.
      vivax infections in clinical samples when used in a PCR assay.

PMID- 8865176
TI  - Adenovirus 41 replication: cell-related differences in viral gene transcription.
AB  - Adenovirus 41 infection of human embryo fibroblasts (HEF cells) leads to an
      abortive replication cycle whereas semi-permissive infection of Chang cells and
      permissive infection of 293 cells leads to the production of infectious
      particles. The aim of this study was to delineate where in the viral life cycle
      the block in replication occurs in non-permissive cells. DNA replication marks
      the onset of the late stage of the replication cycle but synthesis of DNA could
      only be detected when cultures were co-infected with Ad2, suggesting an early
      block in Ad41 replication. In order to map Ad41-specific transcripts produced
      following infection of HEF, Chang and 293 cells, tentative transcription units
      (determined by alignment with the Ad2 and Ad40 transcription maps) were first
      assigned to various plasmids carrying Pstl fragments. These plasmids were used as
      probes to detect Ad41 transcripts that map to these regions. Only transcripts
      mapping to the region between 0 and 12 map units were detected in Ad41 infected
      HEF cells. The level of late transcription was found to be low even in Chang and
      293 cells and we therefore employed a more sensitive method to detect major late
      transcripts in Ad41 infected HEF cells. Transcripts carrying 59 kDa-fibre gene
      specific sequences could be detected using RT-PCR at earlier times in 293 cells
      when compared to Chang cells but were present over a much longer time period in
      the latter cells, and could not be detected in HEF cells. These results are in
      agreement with the results from DNA synthesis in Ad41 infected HEF cells and
      mapping of transcripts to specific regions of the Ad41 genome, confirming that
      the Ad41 block in replication occurs within the early phase of the infectious
      cycle.

PMID- 8865177
TI  - Discrimination of Neospora caninum from Toxoplasma gondii and other apicomplexan
      parasites by hybridization and PCR.
AB  - Neospora caninum is a protozoan parasite which causes neurological problems in
      dogs and abortion in cattle. As N. caninum is difficult to distinguish
      morphologically from Toxoplasma gondii, we developed a molecular tool capable of
      discriminating between the two parasites. Genomic DNA was isolated from in vitro
      cultured N. caninum tachyzoites and cloned into a plasmid vector. Resulting
      colonies were subsequently screened by differential hybridization using N.
      caninum and T. gondii DNA. Two clones were characterized in detail: one clone,
      termed pNc5, was found to be specific for N. caninum whereas the second clone,
      pNc1, hybridized with DNA from both parasites. The sequence of pNc5 was
      determined and different oligonucleotide primers were designed for use in the
      polymerase chain reaction (PCR). A 944 bp fragment was specifically amplified
      from N. caninum DNA, but not from DNA extracted from T. gondii or different
      Sarcocystis species. Positive signals in PCR were obtained with as little as 100
      pg parasite template DNA. In addition, dual PCR with primer pairs specific for N.
      caninum and T. gondii allowed the detection of either parasite in mixed samples.

PMID- 8865178
TI  - Allele frequency distributions at several variable number of tandem repeat (VNTR)
      and short tandem repeat (STR) loci in a restricted Caucasian population from
      south Italy and their evaluation for paternity and forensic use.
AB  - Allele frequencies at six VNTR loci, 11 STR loci, and at the HLA-DQA1 locus were
      evaluated in a well-defined population from Campania (South Italy). The allele
      frequencies of three VNTR loci, 11 STR loci, and the HLA-DQA1 locus were compared
      with data obtained from a general Caucasian reference population in the USA. The
      aim of this study was to determine the power of each single locus and group of
      loci for forensic and paternity testing purposes. Significant differences between
      the allele frequencies of the two populations were found in two VNTR loci, four
      STR loci and in the HLA-DQA1 locus. The two populations were in Hardy-Weinberg
      equilibrium for the STR loci, but as expected, not for some VNTR loci. It was
      also found that: (i) the discriminatory power of two STR systems (nine and 11
      loci, respectively) is similar in the two populations analysed; and (ii) that the
      allele frequencies for the STR systems of a large reference population can always
      be applied to subjects of a small subpopulation. In conclusion, for forensic
      purposes and for paternity testing, most of the 11 STR loci examined can be
      analysed using allele frequencies from a general Caucasian reference population
      without typing subpopulations, whereas the VNTR loci must be subtyped.

PMID- 8865179
TI  - An AvaII polymorphism in exon 5 of the human hepatic triglyceride lipase gene.

PMID- 8865180
TI  - Identification of a BstNI polymorphism in exon 9 of the human hepatic
      triglyceride lipase gene.

PMID- 8865181
TI  - Description of a symptomless cystic fibrosis L346P/M348K compound heterozygous
      Cypriot individual.
AB  - During the past few years we have been testing the hypothesis that Cyprus may
      have been spared many severe cystic fibrosis (CF) cases but not cystic fibrosis
      transmembrane conductance regulator (CFTR) mutations. We have been analysing by
      molecular methods patients with atypical mild phenotypes where CF enters the
      differential diagnosis. With this approach we identified a mutation, L346P, which
      in association with the severe mutation delta F508 or 1677delTA, confers a mild
      and atypical presentation. Recently, we identified another entirely symptomless
      48-year-old individual, with genotype L346P/M348K. The fact that M348K was
      initially identified in a severely affected Italian patient strengthens the
      hypothesis that L346P, a putative mild mutation, is dominant over severe ones.
      One other explanation is that M348K is not a causative defect but a rare
      polymorphism. These findings have important implications for genetic counselling,
      especially when the counselling is sought by concerned couples for prenatal
      diagnostic purposes.

PMID- 8865182
TI  - Differential addressing of 5-HT1A and 5-HT1B receptors in transfected LLC-PK1
      epithelial cells: a model of receptor targeting in neurons.
AB  - Based on the finding that the mechanism of membrane protein sorting may be
      similar in neurons and epithelial cells, we have investigated the localization of
      the 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in Eli Lilly and
      Company canine kidney (LLC-PK1) cells (epithelial cells from pig kidney) stably
      transfected with the corresponding cDNAs. Receptors were characterized by
      radioligand binding, measurement of coupled adenylate cyclase activity and
      immunofluorescene with specific antibodies. Confocal microscopy and cell surface
      biotinylation experiments showed that the 5-hydroxytryptamine1A receptor, which
      is at the somatodendritic level in neurons, was targeted to the basolateral
      surface whereas the 5-hydroxytryptamine1B receptor, which is localized on nerve
      endings, predominated intracellularly. Such a difference in the localization of
      these two receptors suggests that the signal for the differential addressing of 5
      hydroxytryptamine1A and 5-hydroxytryptamine1B receptors is contained within their
      primary sequence and confirms that epithelial cells can be used as a suitable
      model to study receptor targeting in neurons.

PMID- 8865183
TI  - Learning impairment in transgenic mice with central overexpression of
      corticotropin-releasing factor.
AB  - The present studies were designed to test the learning and memory capacities of
      transgenic mice with central overexpression of corticotropin-releasing factor in
      a forced alternation water T-maze task and in the Morris water maze. In T-maze
      testing, littermate control mice reached a criterion of 70% correct responses
      after five days of trials, while the performance of transgenic subjects was still
      random after the same training. In Morris maze testing, control subjects reached
      the submerged platform significantly faster (F(1.48) = 4.51, P < 0.05) after
      three days of trials, while the performance of transgenic mice was unimproved
      over the same period. The deficit in Morris maze performance in transgenic mice
      was reversed when the platform was visible above the surface of the water. Pre
      test administration of the benzodiazepine anxiolytic, chlordiazepoxide (10
      mg/kg), before acquisition training also produced a significant (F(4.40) = 16.61,
      P < 0.001) and persistent improvement in Morris maze performance in transgenic
      mice when compared to vehicle-treated transgenic litter mates. Finally, there was
      no evidence of hippocampal cell loss in transgenic brains. The results suggest
      that corticotropin-releasing factor-overexpressing mice exhibit a profound
      learning deficit without sensory or motor-related impairments, and that memory
      plasticity can be restored by anxiolytic pre-treatment. Thus, constitutive
      overabundance of brain corticotropin-releasing factor may produce
      hyperemotionality that interferes with learned behaviors. Stress-related
      disorders characterized by co-morbid deficits in learning/memory may benefit from
      pharmacological normalization of brain corticotropin-releasing factor systems.

PMID- 8865184
TI  - Hippocampal-dependent learning and experience-dependent activation of the
      hippocampus are preferentially disrupted by ethanol.
AB  - A classical fear conditioning paradigm was used to examine the effect of acute
      ethanol on the acquisition of context conditioning, a hippocampal-dependent
      associative task, and tone conditioning, a hippocampal-independent task.
      Administration of ethanol before the presentation of seven tone-shock pairings
      severely disrupted the acquisition of context conditioning, but had only a slight
      effect on tone conditioning, when conditioned fear was measured 48 h later. This
      effect was dose dependent: a dose of 0.5 g/kg had no effect on either context or
      tone conditioning, while doses of 1.0 and 1.5 g/kg disrupted context conditioning
      by 78-86%, and tone conditioning by 9-17%. Subsequent experiments indicated that
      ethanol's preferential effect on context conditioning could not be attributed to
      the fact that context conditioning is weaker than tone conditioning, ethanol
      induced changes in motivational state or state-dependent learning. The effect of
      ethanol on stimulus-induced increases in hippocampal and neocortical expression
      of c-fos mRNA, a marker for changes in metabolic neuronal activity, was also
      examined. Ethanol completely blocked the induction of hippocampal c-fos mRNA by
      exposure to the conditioning context alone or seven tone-shock pairings, but only
      attenuated neocortical responses to these stimuli. Together, these results
      suggest that ethanol disrupts hippocampal-dependent learning by preferentially
      impairing stimulus processing at the level of the hippocampus.

PMID- 8865185
TI  - Involvement of silent synapses in the induction of long-term potentiation and
      long-term depression in neocortical and hippocampal neurons.
AB  - Changes in the latency of small excitatory postsynaptic potentials were observed
      in association with induction of long-term modifications of synaptic transmission
      in slices of rat neocortex and guinea-pig hippocampus. After potentiation
      response latency decreased in 3/10 cases in the neocortex and in 6/24 cases in
      the hippocampus, and increased after depression in 4/8 cases in the neocortex.
      These latency changes could not be attributed to changes in presynaptic fibre
      excitability, monosynaptic inhibition, release kinetics or activation kinetics of
      postsynaptic ion channels. We conclude therefore that potentiation led to the
      activation of previously silent synapses of fast-conducting afferents and
      depression to the inactivation of previously functional synapses. Thus,
      neocortical and hippocampal synapses can be in a non-functional state, and
      regimes that induce long-term potentiation and depression not only change the
      efficacy of synapses but also alter their functional state.

PMID- 8865186
TI  - Hippocampal long-term potentiation and spatial learning in the rat: effects of
      GABAB receptor blockade.
AB  - This series of experiments assessed the role of GABAB receptors in the induction
      of long-term potentiation in the dentate gyrus in vivo, and spatial learning and
      memory in three different tasks. In urethane-anesthetized rats, the GABAB
      receptor antagonist CGP 46381 was injected intraperitoneally at a dose which
      effectively suppressed GABAB-mediated paired pulse disinhibition. Theta-burst
      stimulation reliably produced long-term potentiation in control rats. However,
      GABAB receptor blockade significantly suppressed the induction of long-term
      potentiation in the dentate gyrus. To compare the results of the long-term
      potentiation experiments with behavior, we assessed the performance of rats on
      several spatial learning and memory tasks in the presence of CGP 46381. We found
      that the working memory performance of highly trained rats on the eight-arm
      radial maze was unaffected by CGP 46381. There was also no effect of GABAB
      receptor blockade on learning in the eight-arm maze using a five-trial repeated
      acquisition paradigm. However, when we tested spatial learning in naive rats
      using a mildly stressful water maze task, we found that CGP 46381 substantially
      impaired both the latency to find the platform and the path-length travelled in
      the maze during acquisition. CGP 46381-treated rats took longer to learn the
      location of the escape platform and travelled a greater distance over the
      acquisition trials. These data demonstrate that GABAB receptor blockade results
      in a suppression of hippocampal long-term potentiation in vivo and impairs
      spatial learning in a task where stress may be a component of performance.

PMID- 8865187
TI  - Aging-related subunit expression changes of the GABAA receptor in the rat
      hippocampus.
AB  - Aging-related changes in the subunit expression of some hippocampal GABAA
      receptors have been found. Quantitative in situ hybridization has revealed that
      alpha 1, subunit messenger RNA expression was significantly increased in the
      hippocampus (34%) of old rats. The largest increases were observed in the dentate
      gyrus (76%) and in the CA1 field (30%). Quantitative immunocytochemistry also
      showed increased protein expression of the alpha 1 subunit in the dentate gyrus
      (19%) and CA1 (14%) of old rats. The increased alpha 1 messenger RNA and protein
      expression led to increased proportions of assembled GABAA receptors that
      contained alpha 1 subunits, as revealed by quantitative immunoprecipitation of
      (3H)flunitrazepam and (3H)muscimol binding. In contrast, there were no
      significant changes in the expression of beta 2, beta 3 and total gamma 2 (gamma
      2S + gamma 2L) subunits, although a slightly increased expression of gamma 2L
      peptide was detected in the hippocampus proper (7%), but not in the dentate
      gyrus. The results are consistent with the notion that in the rat hippocampus
      there is an aging-related change in the subunit composition of some GABAA
      receptors.

PMID- 8865188
TI  - Ionotropic glutamate receptor subtypes in the aged memory-impaired and unimpaired
      Long-Evans rat.
AB  - The comparative quantitative autoradiographic distribution of ionotropic
      glutamate receptor subtypes were investigated in young adults (six months) and
      aged (24-25 months) cognitively impaired and unimpaired male Long-Evans rats.
      Aged rats were behaviorally characterized as either cognitively impaired or
      unimpaired based upon their performances in the Morris water maze task compared
      to the young adult controls. The status of the N-methyl-D-aspartate,
      [125I]dizocilpine maleate, [3H]kainate and amino-3-hydroxy-5-methylisoxasole-4
      propionate (AMPA, [3H]AMPA) receptor binding sites were then established in these
      three subgroups of animals as a function of their cognitive performance in the
      Morris water maze task. The apparent densities of both N-methyl-D
      aspartate/[125I]dizocilpine maleate and kainate binding sites were significantly
      decreased in various regions of the aged rat brain. Marked losses in
      [125I]dizocilpine maleate binding sites were observed in outer laminae of the
      frontal, parietal and temporal cortices, and the stratum radiatum of the CA3
      subfield of the hippocampus. Interestingly, losses in [125I]dizocilpine maleate
      binding sites were generally most evident in the cognitively unimpaired aged
      subgroup, suggesting a possible inverse relationship between losses of this
      receptor subtype and cognitive performances in the Morris water maze task. The
      levels of [3H]kainate binding were most significantly diminished in various
      cortical and hippocampal areas as well as the striatum and septal nuclei of both
      groups of aged rats. In contrast, the apparent density of [3H]AMPA binding was
      increased in most hippocampal subfields and the superficial laminae of the
      occipital cortex of the cognitively impaired vs young adult rats. Changes in
      [3H]AMPA labeling failed to reach significance in the unimpaired cohort. Taken
      together, these results show that while losses in [3H]kainate binding were
      similar in both subgroups of aged rats, differences were seen with respect to
      cognitive status for both [125I]dizocilpine maleate/N-methyl-D-aspartate and
      [3H]AMPA binding sites. Decreases in [125I]dizocilpine maleate binding sites were
      mostly restricted to cortical areas of cognitively unimpaired rats, while
      increases in the AMPA binding subtype were seen in the memory-impaired subgroup.
      It would thus appear that changes in N-methyl-D-aspartate and AMPA receptor
      subtypes may be more critical than alterations in kainate binding sites for the
      emergence of the functional deficits seen in the aged cognitively impaired rat.

PMID- 8865189
TI  - Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of
      spontaneous alternation behavior in mice.
AB  - The activation of N-methyl-D-aspartate receptors induces the synthesis of nitric
      oxide, which activates soluble guanylate cyclase and leads to the formation of
      cyclic GMP in the brain. The inhibition of nitric oxide production, as well as
      the blockade of N-methyl-D-aspartate receptors, has been reported to prevent the
      induction of hippocampal long-term potentiation and learning and memory formation
      in vivo, although the effects of inhibitors of nitric oxide synthase are still
      controversial. We investigated the putative role of nitric oxide and cyclic GMP
      in dizocilpine-induced memory impairment in mice. The nitric oxide synthase
      inhibitors, NG-nitro-L-arginine methyl ester and 7-nitro indazole, as well as
      dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, dose
      dependently impaired spatial working memory in mice, assessed by their
      spontaneous alternation behavior in a Y-maze. The inhibitory effects of both NG
      nitro-L-arginine methyl ester and dizocilpine on their behavior were completely
      reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced
      by treatment with dizocilpine. NG-Nitro-L-arginine methyl ester and 7-nitro
      indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and
      cerebellum, and the suppressive effect of NG-nitro-L-arginine methyl ester on
      cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment
      with L-arginine. Cyclic AMP levels in the brain were not affected by treatment
      with either dizocilpine, NG-nitro-L-arginine methyl ester, or 7-nitro indazole.
      Neither NG-nitro-L-arginine methyl ester nor L-arginine had any effect on
      monoamine and acetylcholine metabolism in the brain. These results suggest that
      the reduction in nitric oxide/cyclic GMP production in the brain may be
      responsible for dizocilpine-induced impairment of spontaneous alternation
      behavior in a Y-maze.

PMID- 8865190
TI  - Quantitative morphology of physiologically identified and intracellularly labeled
      neurons from the guinea-pig laterodorsal tegmental nucleus in vitro.
AB  - Mesopontine cholinergic neurons have been implicated in the initiation and
      maintenance of rapid eye movement sleep via their efferent connections to the
      thalamus and the medial pontine reticular formation. As a first step toward
      understanding how these modulatory neurons integrate synaptic input, we have
      investigated the dendritic architecture of laterodorsal tegmental nucleus
      neurons. The principal cells of the guinea-pig laterodorsal tegmental nucleus
      were identified electrophysiologically in a brain slice preparation, then were
      intracellularly injected with biocytin and reconstructed using a computer-aided
      tracing system. The somata were large (27 +/- 3 microns; n = 11) and gave rise to
      an average of 4.8 primary dendrites which, in most cases, emerged from the soma
      in a pattern that was radially symmetric in the plane of the slice. Primary
      dendrites had an average of 3.7 endings. A single axon arose from either the soma
      or a proximal dendrite and exited the nucleus with a medial and/or lateral
      trajectory. Some axons also gave rise to a local terminal plexus composed of fine
      fibers bearing numerous punctate swellings that ramified profusely within the
      neuron's dendritic field. Total dendritic area averaged about 10(5) microns2, and
      therefore the average contribution of the soma to the total surface area (20%)
      was significantly larger than the values reported for many other cell types.
      Dendritic diameters were non-uniform in three respects. Some processes were
      sparsely spiny. Most processes were varicose, with the degree of varicosity
      increasing substantially in secondary and tertiary dendritic segments. There was
      also a large degree of taper in dendritic processes; those processes with a non
      negative taper had an average diameter decrease of 40 +/- 25%. Dendritic
      processes deviated from the criteria necessary for a Rall equivalent cylinder
      approximation due to non-uniformity in morphotonic path length, failure to
      conform to the Rall 3/2 branching rule and non-uniformity of dendritic diameter.
      An analysis was done to assess the impact of dendritic varicosities on the
      extraction of cable parameters for these cells. Voltage traces were simulated by
      solving the cable equation for a varicose dendrite and then membrane parameters
      were recovered using an equivalent cylinder model. Errors in the extracted values
      of specific membrane conductance and specific membrane capacitance were quite
      small (< or = 5%), while larger errors were seen for electrotonic length (< or =
      21%) and intracellular resistivity (< or = 5%). These data indicate that the
      principal cells of the laterodorsal tegmental nucleus, while possessing a
      relatively simple dendritic structure in terms of number and branchiness of
      dendrites, display a heterogeneity of dendritic process types. Processes range
      from smooth to markedly varicose, and can be aspiny or sparsely spiny. The
      possibility that the dendritic varicosities function as sites of either
      electrical or chemical compartmentalization is discussed. The degree of error
      resulting from a Rall equivalent cylinder approximation in light of these
      varicosities indicated that a generalized cable model approach may prove more
      effective in estimating their cable parameters.

PMID- 8865191
TI  - Electrical stimulation of the cholinergic laterodorsal tegmental nucleus elicits
      scopolamine-sensitive excitatory postsynaptic potentials in medial pontine
      reticular formation neurons.
AB  - A large and consistent body of data implicates mesopontine cholinergic neurons in
      the production of rapid eye movement sleep, and indicates that many rapid eye
      movement sleep events are mediated by activation of pontine reticular formation
      neurons. There is anatomical evidence for projections from the mesopontine
      cholinergic nuclei to the pontine reticular formation, but no study has shown
      that stimulation of this cholinergic zone produces excitatory postsynaptic
      potentials in pontine reticular formation neurons. In the present study,
      intracellular recording were made from 168 pontine reticular formation neurons,
      identified by antidromic activation from the bulbar reticular formation and by
      neurobiotin intracellular labeling, in acutely anesthetized cats. The effects of
      single-pulse electrical stimulation of the laterodorsal tegmental nucleus portion
      of the ipsilateral mesopontine cholinergic zone were evaluated in these neurons.
      Under urethane anesthesia this stimulation produced, in 21 of 22 recorded
      neurons, long-latency excitatory postsynaptic potentials (mean = 3 ms),
      consistent with the conduction velocity of unmyelinated cholinergic fibers
      (measured conduction velocity was 2 m/s). This excitatory postsynaptic potential
      was virtually abolished by intravenous administration of the muscarinic
      cholinergic receptor blocker scopolamine (n = 40 neurons), and by acute cuts
      separating the laterodorsal tegmental nucleus and the recorded neurons (n = 40).
      In contrast, a short-latency excitatory postsynaptic potential (0.7-1.5 ms) was
      not reduced in amplitude by scopolamine and could still be elicited following
      acute transverse cuts. Unlike the longer-latency excitatory postsynaptic
      potential, its amplitude was not reduced by barbiturate anesthesia. These data,
      suggesting the presence of an excitatory, cholinergic laterodorsal tegmental
      nucleus projection to the pontine reticular formation, provide further support to
      other lines of evidence implicating mesopontine cholinergic neurons in the
      production of rapid eye movement sleep, and are compatible with a model of rapid
      eye movement sleep generation in which a key element is mesopontine cholinergic
      input depolarizing and increasing the excitability of reticular core neurons.

PMID- 8865192
TI  - Electrophysiological, behavioural and biochemical evidence for activation of
      brain noradrenergic systems following neurokinin NK3 receptor stimulation.
AB  - The objective of the present in vitro and in vivo experiments was to examine the
      involvement of neurokinin NK3 receptors in the regulation of the noradrenergic
      function in gerbils and guinea-pigs. Application of senktide, a peptide NK3
      receptor agonist, on guinea-pig locus coeruleus slices increased the firing rate
      of presumed noradrenergic neurons (EC50 = 26 nM) in a concentration-dependent
      manner. Given i.c.v., senktide (0.5-2 micrograms) and (MePhe7)neurokinin B (1-10
      micrograms), another NK3 receptor agonist, reduced exploratory behaviour in
      gerbils in a dose-dependent manner (2 micrograms of senktide producing a 50%
      reduction of locomotor activity and rearing). In vivo microdialysis experiments
      in urethane-anaesthetized guinea-pigs showed that senktide (2-8 micrograms
      i.c.v.) induced a dose-dependent increase in norepinephrine release in the medial
      prefrontal cortex. The electrophysiological, behavioural and biochemical changes
      elicited by senktide were concentration- or dose-dependently reduce by SR 142801,
      the selective non-peptide NK3 receptor antagonist. In the locus coeruleus slice
      preparation, complete antagonism of senktide (30 nM) was observed with 50 nM of
      SR 142801, while injected i.p. (0.1-1 mg/kg) it abolished the senktide-induced
      norepinephrine release in guinea-pigs. In gerbils, SR 142801 (1-10 mg/kg i.p.)
      reversed the reduction of exploratory behaviour induced by senktide (1
      microgram). By contrast, the 100-fold less active enantiomer, SR 142806, did not
      exert any antagonism in these models. Finally, the reduction of exploratory
      behaviour in gerbils was found to be reversed by prazosin (0.25-2.56
      micrograms/kg i.p.) and to some extent by clonidine, drugs known to depress
      noradrenergic function. All these experiments strongly support the hypothesis
      that brain noradrenergic neurons can be activated by stimulation of neurokinin
      NK3 receptors.

PMID- 8865193
TI  - Importance of the ventrolateral region of the periaqueductal gray and adjacent
      tegmentum in the control of paradoxical sleep as studied by muscimol
      microinjections in the cat.
AB  - It has been demonstrated that coagulation in the area of the periaqueductal gray
      induces a marked increase in paradoxical sleep in the cat [Petitjean F. et al,
      (1975) brain Res. 88, 439-453]. This effect was obtained either by the
      destruction of ascending or descending fibres or by the lesion of a specific
      group of local neurons. To assess the role of these neurons, muscimol (0.5
      microgram/0.5 microliter) was injected bilaterally in 31 cats in this area of the
      periaqueductal gray. Polygraphic recordings were performed before and after
      injections. Following muscimol (GABAA agonist) injection, there was a consistent
      increase in paradoxical sleep lasting 269 +/- 8 min (mean +/- S.E.M.), with a
      latency of 31 +/- 2 min. The increase varied from small (20-30%) to medium (30
      50%) to large (50-100% of the recording time), depending on the injection site.
      The intensity of hypersomnia was correlated with the site of the injection. That
      is, the most profound hypersomnia was obtained when muscimol was injected in the
      vicinity of a target area which lies in the ventrolateral periaqueductal gray (at
      the level of the fourth nucleus) and in the reticular formation situated
      immediately below. Similar effects were also obtained in insomniac cats
      pretreated with p-chlorophenylalanine and in cats whose brainstem was transected
      3 mm rostral to the injection site. Injections of baclofen, a GABAB agonist (0.25
      5 micrograms), did not alter the quantity of paradoxical sleep, whereas
      injections of bicuculline, a GABAA antagonist, significantly decreased the
      quantity of paradoxical sleep at the doses of 0.2-2 micrograms. It was concluded
      that inactivation of ventrolateral periaqueductal gray neurons induces a very
      important increase in paradoxical sleep. The exact mechanisms of this effect
      remain to be investigated.

PMID- 8865194
TI  - Compartmentalization of calbindin and parvalbumin in different parts of rat
      rubrospinal neurons.
AB  - The distribution of calbindin-immunoreactive neurons in the red nucleus and the
      subcellular distribution of the calbindin and parvalbumin in tracer-identified
      rubrospinal neurons of the rat were studied. Only a fraction of the retrogradely
      labelled rubrospinal neurons was found to contain calbindin. These neurons filled
      the caudal part of the red nucleus and also appeared sporadically along the
      ventromedial border of the middle segment of the red nucleus. In addition to the
      somata, calbindin was found in the dendritic arbors of tracer-identified
      rubrospinal neurons, revealed by injecting the fluorescent dye Lucifer Yellow
      into their cell bodies. The axons of rubrospinal neurons located in the caudal
      red nucleus were marked by performing anterograde tracing with fluorescent
      dextran tracer in freshly prepared brainstem slices. Parvalbumin was found to
      locate in swellings along these tracer-identified axons as well as at their cut
      ends. The results indicate that calbindin and parvalbumin are segregated to the
      somadendritic and axonal compartments of the rat rubrospinal neurons,
      respectively. This anatomical segregation suggests that they may have different
      functions in neurons.

PMID- 8865195
TI  - Dopamine D2 receptors are organized in bands in normal human temporal cortex.
AB  - Previous studies have documented a highly compartmentalized and laminar
      organization of dopamine D2 receptors in human hippocampus, entorhinal and
      perirhinal cortices. These areas receive input from regions of polysensory
      association cortices of the superior and inferior temporal sulci that evidence
      functional modules identified by other techniques. We examined the isocortical
      regions of temporal lobe for an equally well-differentiated pattern of D2
      receptor expression as observed in their paleocortical temporal lobe targets.
      Using quantitative autoradiography we identified an organization of three
      dimensional bands of high concentrations of dopamine D2 receptors throughout the
      rostral-caudal extent of the normal human temporal cortex. In the coronal plane,
      these D2 receptor-enriched bands had a columnar appearance with the concentration
      of D2 receptors almost two-fold higher within the bands than in the immediately
      adjacent cortex. These D2 receptor-enriched bands had a distinct laminar
      appearance with a paucity of [125I]epidepride binding to D2 receptors over the
      granule cell layer and higher concentrations of D2 receptors in laminae III and V
      than in the immediately adjacent cortex. They had a consistent width (mean width
      of 2.83 +/- 0.62 mm) in the coronal plane, but had their long axes in the
      rostrocaudal plane (some were at least 2500 microns in length). Hence, they exist
      as three-dimensional D2 receptor-enriched and receptor-poor modules with their
      long axes in the rostrocaudal plane. Tyrosine hydroxylase-immunoreactive fibers
      were observed to cross orthogonally to the long axes of the D2 receptor enriched
      bands. Other monoamine receptors (beta-adrenergic, 5-hydroxytryptamine2), and
      markers for myelin (anti-myelin basic protein immunohistochemistry), glia (5'
      nucleotidase), and energy metabolism (cytochrome oxidase) showed a laminar
      organization but failed to demarcate the D2 receptor-enriched bands. The majority
      of these D2 receptor-enriched bands were observed in the lateral and inferior
      aspects of the superior temporal gyrus, less frequently on the lateral surface of
      the inferior temporal gyrus and the parahippocampal cortices (Brodmann's area 22,
      42 and 20, 21, 37). They were absent from primary auditory cortex (Brodmann's
      41). The present study is the first known observation of a modular organization
      of synaptic elements, identified by D2 receptors, in non-primary sensory cortices
      of any species. The dopamine D2 receptor-enriched bands were found in regions
      previously identified as having functional modules that underlie feature
      extraction. Hence, D2 receptor-enriched and receptor-poor modules may provide a
      mechanism for functional regulation of compartments within these regions by
      dopamine.

PMID- 8865196
TI  - Activation of dopaminergic D1 receptors promotes morphogenesis of developing
      striatal neurons.
AB  - The early dopaminergic input from the midbrain may play an important role in the
      development of the basal ganglia. We therefore investigated whether and how
      dopamine affects the morphogenesis of striatal target neurons. Dissociated cell
      cultures of embryonic day 17 rat striatum were raised for seven days. Cells were
      then incubated with dopamine or various receptor-specific ligands for 1 h. At
      various times after termination of the treatment, cells were immunostained for
      growth-associated protein-43. Morphological parameters including numbers of
      growth cones, length of neurites, number of bifurcations, and neuronal soma size
      were assessed by means of a computer-based morphometric device. Treatment with
      dopamine in low concentrations as well as with the D1-like receptor agonist SKF
      38393 increased the numbers of growth cones and neurite length and arborization.
      The morphogenetic effect took several hours to evolve and remained stable for at
      least 24 h. It could be blocked by the D1-like receptor antagonist SCH 23390 or
      by cycloheximide but not by pretreatment of the cultures with tetrodotoxin. The
      D2-like receptor agonist quinpirole had no effect on the morphological parameters
      and did not contribute to that of SKF 38393. Dopamine and SKF 38393 but not
      quinpirole also induced an increase in the number of neurons immunoreactive for
      Fos-like proteins. However, this effect was restricted to growth-associated
      protein-43-negative neurons. This is the first observation of a positive
      regulatory effect of D1-like receptors on neuronal morphogenesis. We conclude
      that the changes reflect true differentiation rather than short-term modulation
      of cellular properties and that c-fos induction is not an obligatory step in the
      transduction pathway coupling D1-like receptors to neurite outgrowth. Our results
      suggest that the differentiation of embryonic striatal neurons is promoted by the
      dopaminergic nigrostriatal projection through D1-like receptors.

PMID- 8865197
TI  - Reduced glucose metabolism enhances the glutamate-evoked release of arachidonic
      acid from striatal neurons.
AB  - Glucose deprivation potentiates the glutamate receptor-evoked release of
      arachidonic acid from cultured mouse striatal neurons. In this study we
      investigated whether this potentiation would be modified by the end-products of
      glycolysis. These enhanced responses were completely reversed by the addition of
      increasing concentrations of either lactate or pyruvate. This reversal was not
      due to increased osmolarity as substituting sucrose for lactate or pyruvate did
      not mimic their effects. In contrast, in the presence of glucose, neither lactate
      nor pyruvate was effective. Furthermore, these monocarboxylic acids rescued
      neuronal respiration in the absence of glucose. Inhibiting glycolysis with
      iodoacetate in the presence of glucose reproduced the potentiated glutamate
      evoked release of arachidonic acid observed following glucose deprivation and
      reduced neuronal respiration to the same extent as that observed in the absence
      of glucose. All of these effects were overcome by the addition of either lactate
      or pyruvate. The reversal of the potentiated glutamate-evoked release of
      arachidonic acid by lactate or pyruvate was inhibited by a specific inhibitor of
      monocarboxylic acid transport, alpha-cyano-4-hydroxycinnamic acid, suggesting
      that lactate and pyruvate act intracellularly. Therefore, we propose that the
      enhanced release of arachidonic acid evoked by glutamate during glucose
      deprivation results from reduced glycolysis and hence from a depletion of lactate
      or pyruvate.

PMID- 8865198
TI  - Methylenedioxymethamphetamine-induced inhibition of neuronal firing in the
      nucleus accumbens is mediated by both serotonin and dopamine.
AB  - Methylenedioxymethamphetamine (MDMA) is a mood-altering, legally restricted drug
      that has been reported to inhibit glutamate-evoked firing of cells in the nucleus
      accumbens. This study used extracellular recording combined with
      microiontophoresis to examine whether the inhibitory effect of MDMA on neuronal
      firing in the nucleus accumbens is mediated by serotonin and/or dopamine.
      Serotonin and serotonin agonists with relative selectivity for the receptor
      subtypes 5-HT1A, 5-HT1B, 5-HT2A/2C and 5-HT3 all significantly (P < 0.01)
      inhibited glutamate-evoked firing of cells in the nucleus accumbens compared to
      the effects of an acidic saline control solution (30-60 nA, 60 s ejection
      currents for all). The current (dose)-dependent inhibition produced by the
      serotonin agonists did not differ significantly from the inhibition produced by
      MDMA except for the 5-HT1A agonist 8-hydroxy-(2-di-n-propylamino) tetralin, which
      inhibited glutamate-evoked firing significantly more than MDMA or any of the
      other serotonin agonists. At the highest ejection current tested (60 nA, 60 s),
      glutamate-evoked firing was inhibited by MDMA in 94% of tested cells, by
      serotonin in 80% of tested cells and by the serotonin receptor subtype agonists
      in 95-100% of the tested cells. In addition to being mimicked by serotonin and
      serotonin agonists, MDMA-induced inhibition of glutamate-evoked firing in the
      nucleus accumbens was partially blocked by the serotonin antagonists ketanserin
      (100% of tested cells), methysergide (80% of tested cells), methiothepin (100% of
      tested cells) and WAY100135 (100% of tested cells). Furthermore, application of
      the serotonin uptake blocker fluoxetine, which prevents MDMA-induced serotonin
      release, also significantly attenuated MDMA-induced inhibition of glutamate
      evoked firing in all of the cells that were tested. These observations suggest
      that MDMA-induced inhibition of nucleus accumbens cell firing is at least
      partially mediated by serotonin. Depletion of dopamine by pretreatment with the
      neurotoxin 6-hydroxydopamine and the synthesis inhibitor alpha-methyl-p-tyrosine
      blocked the inhibition of glutamate-evoked firing produced by MDMA applied with
      low ejection currents (30-40 nA, 60 s). However, this dopamine depletion had no
      effect on inhibition of glutamate-evoked firing produced by serotonin ejected
      with low or high currents (20-60 nA, 60 s). These results suggest that both
      dopamine release and an intermediate step of MDMA-induced serotonin release are
      necessary for the inhibitory effects of MDMA on neuronal excitability in the
      nucleus accumbens. The dopamine- and serotonin-mediated inhibitory effects of
      MDMA on glutamate-evoked firing of nucleus accumbens cells may play a role in the
      mood-altering properties of this increasingly popular drug.

PMID- 8865199
TI  - Neuronal spike activity in rat nucleus accumbens during cocaine self
      administration under different fixed-ratio schedules.
AB  - Chronic ensemble recording techniques were used to investigate neuronal activity
      in the nucleus accumbens in freely moving rats during different cocaine self
      administration schedules. The issue of concern in this study was the role of
      nucleus accumbens in initiating and sustaining cocaine self-administration.
      Specifically, to determine the nature of the neuronal activity, either motor or
      motivational, which precedes the multiple bar presses required to self-administer
      cocaine and of the post-lever press neuronal response, we used conventional fixed
      ratio-5, fixed ratio-10, and modified fixed ratio-3 schedules. In the modified
      fixed ratio-3 schedule, the first lever press resulted in retraction of the lever
      for 2 s; the second lever press retracted the lever and turned on a cue light;
      the third lever press turned off the cue light and delivered cocaine (1.0 mg/kg)
      intravenously. In the fixed ratio-5 and -10 schedules, rats continuously pressed
      the lever 5 or 10 times, respectively, to obtain a single infusion of cocaine.
      Phasic alterations in neural spike activity were observed in 50% of nucleus
      accumbens neurons before (termed "anticipatory" responses) and after lever
      pressing for cocaine self-administration. Neurons with anticipatory responses
      typically exhibited such responses for all lever presses in the modified fixed
      ratio-3, fixed ratio-5, and fixed ratio-10 schedules, but instances were found
      when the activity correlate was absent. In addition, some neurons had a prominent
      alteration in firing rate lasting 1-5 min after cocaine self-administration, and
      some of these neurons also had anticipatory responses. When cocaine was
      eliminated during self-administration sessions, the post-lever press inhibitory
      responses were largely abolished or even reversed, whereas anticipatory responses
      were not markedly changed when rapid lever presses occurred before behavior
      ceased. Post-cocaine inhibitory responses compared between self-administered and
      passively administered cocaine were not significantly different between these two
      conditions. The results suggest that nucleus accumbens may be involved in
      initiating general reward-seeking behaviors and action which are not exclusively
      associated with cocaine self-administration. Moreover, the neuronal responses in
      the nucleus accumbens to cocaine self-administration may play an essential role
      in maintaining cocaine reinforcement.

PMID- 8865200
TI  - Electrophysiological investigation of adenosine trisphosphate-sensitive potassium
      channels in the rat substantia nigra pars reticulata.
AB  - Adenosine trisphosphate-sensitive potassium (K-ATP) channels in the substantia
      nigra pars reticulata were studied in rat brain slices using whole-cell patch
      clamp recording. Substantia nigra pars reticula neurons were identified as such
      by their spontaneous action potential firing at mean rate of 15.3 Hz1 virtual
      absence of hyperpolarization-activated inward current Ih1 and unresponsiveness to
      dopamine (30 microM), quinirole (10 microM) and (Met)enkephalin (10 microM).
      Intracellular dialysis with Mg(2+0-ATP-free pipette solutions caused a slowly
      developing membrane hyperpolarization (13 +/- 4 mV), accompanied by a cessation
      of action potential firing, or an outward current (79 +/- 30 pA at around -60
      mV), which were reversed b the sulphonylurea K-ATO channel blockers tolbutamide
      (100 microM) and glibenclamide (3 microM). When Mg(2+0-ATP (2 mM) was included in
      the recording pipette no membrane hyperpolarization or outward current was
      observed. Neither the sulphonylureas nor the potassium channel activator
      lemakalim (200 MicroM) altered membrane potential, firing rate or holding current
      under these recording conditions. The outward current induced by dialysis with
      Mg(2+)-ATP-free solutions reversed polarity negative to -94 +/- 9 mV (9 cells),
      close to the estimated K+ equilibrium potential (-105 mV) for the conditions
      used, and was associated with a conductance increase that was blocked by Ba2+
      (100 microM). The current blocked by the sulphonylureas had a similar reversal
      potential (-97 +/- 7 MV; 13 cells), and both currents were voltage independent
      over the range -50 to -100 mV with slope conductance of approximately 2.0 nS.
      Outward synaptic current were evoked by single shock electrical simulation, in
      the presence of glutamate receptor antagonists, at a holding potential of -50 mV.
      These synaptic currents were blocked by bicuculline (10 microM) and reversed
      polarity at around -65 mV, close to the Cl- equilibrium potential, and were thus
      mediated by GABAA receptors. They were reversibly depressed by 37 +/- 14% in
      lemakalim (200 microM) in 6/12 cells tested, an effect that was partially
      reversed by tolbutamide (200 microM). It is concluded that functional K-ATP
      channels are present both presynaptically and postsynaptically in the substantia
      nigra pars reticulata. Postsynaptic K-ATP channels may control excitability in
      conditions where intracellular ATP is reduced, whereas presynaptic K-ATP
      channels, sensitive to the potassium channel activator lemakalim, can modulate
      the release of GABA, which probably arises from fibres of extranigral origin.
      Pharmacological differences between these two sites could be exploited to treat
      epilepsies, dyskinesias and akinesia.

PMID- 8865201
TI  - Immortalized cerebellar cells can be induced to display mature neuronal
      characteristics.
AB  - We have established and characterized a cell line (designated Cb-E1A) that can be
      induced to display a variety of neuronal characteristics under simple culture
      conditions. This cell line was generated by retroviral-mediated gene transfer of
      the adenovirus 12S E1A-immortalizing gene in cerebellar cells isolated from one
      week-old rats. Actively dividing cells express the E1A adenovirus protein, and
      exhibit minimal expression of glial cell markers and low level expression of
      neuronal cell markers. The immortalized cells can be induced to differentiate by
      culture in an alternative depolarizing medium or calcium ionophore-containing
      medium. This caused the expression of neuronal markers to increase rapidly, while
      glial markers remain unchanged. Under these culture conditions, the Cb-E1A cells
      also display a variety of other characteristics which suggest that they may
      provide a good model system for differentiated cerebellar granule neurons. Such
      neuronal characteristics include a reduction or cessation of mitosis and an
      increased susceptibility to glutamate toxicity. We think that this novel cell
      line and differentiation strategy will facilitate future studies of the cellular
      mechanisms involved in a wide variety of neuronal functions, including
      development and neurodegenerative disease.

PMID- 8865202
TI  - Localization and developmental changes in the neuron-specific cyclin-dependent
      kinase 5 activator (p35nck5a) in the rat brain.
AB  - Mammalian brains contain a cde2-like protein kinase which is a heterodimer of
      cyclin-dependent kinase 5 (Cdk5) and a brain-specific regulatory subunit with a
      molecular weight of 35,000. In this study, we examined the temporal and spatial
      expression patterns of p35nck5a in the developing rat brain. Northern blot
      analysis showed that p35nck5a messenger RNA expression was low in the brain of 12
      day postcoitum rats, and increased to a much higher level from 18 days postcoitum
      to two weeks after birth, and then declined at three weeks after birth. These
      developmental changes in p35nck5a expression correlated with the changes in Cdk5
      associated kinase activity during brain development. These data suggest that
      p35nck5a is the specific activator for Cdk5 in the brain. Immunohistochemical and
      in situ hybridization studies demonstrated the presence of p35nck5a protein in
      postmitotic neurons but not in glial cells at all stages of brain development,
      indicating that p35nck5a is a neuron-specific protein. In the adult brain, the
      protein was rich in cell bodies and dendrites, and only very low amounts were
      detected in axons. In fetal and neonatal brains, however, axonal pathways such as
      the corpus callosum and external capsule were also stained with anti-p35nck5a
      antibody. Our findings suggest that p35nck5a is neuron specific, and a specific
      activator for Cdk5, and the subcellular localization of the two is strictly
      regulated depending on brain development. Neuronal Cdc2-like kinase may play key
      roles in neuronal maturation, synaptic formation, and neuronal plasticity.

PMID- 8865204
TI  - Anatomical studies of DNA fragmentation in rat brain after systemic kainate
      administration.
AB  - Rats treated systemically with kainate develop stereotyped epileptic seizures
      involving mainly limbic structures that may last for hours. This model of limbic
      status epilepticus has been widely studied using classical neuropathological
      techniques. We used in situ nick translation histochemistry to examine patterns
      of DNA fragmentation in this model. We found a stereotyped and reproducible
      pattern of neuronal populations that demonstrate evidence of DNA fragmentation
      from 24 h to one week after kainate treatment. Neither blockade of new protein
      synthesis nor blockade of the N-methyl-D-aspartate-type glutamate receptors
      significantly altered this response. Moreover, we saw no evidence of the regular
      internucleosomal cleavage of DNA that produces a characteristic laddered
      appearance of 180-200 bp DNA fragments after gel electrophoresis in samples
      obtained from microdissected affected regions. These studies suggest that DNA
      fragmentation after systemic kainate-induced seizures is not the result of
      programmed cell death. This assay may be useful for quantitative testing of both
      neuroprotective agents and mechanistic hypotheses.

PMID- 8865203
TI  - Interaction of insulin-like growth factor-I and estradiol signaling pathways on
      hypothalamic neuronal differentiation.
AB  - Neurotrophic effects of estradiol and insulin-like growth factor-I were assessed
      in primary cultures from fetal rat hypothalamus. Cultured neurons were
      immunostained with an antibody for the microtubule-associated protein-2. While
      both estradiol and insulin-like growth factor-I increased the number of
      microtubule-associated protein-2-immunoreactive neurons and the extension of
      immunoreactive processes, the effect of these two factors was not additive. The
      estradiol-induced increases in neuronal numbers and extension of neuronal
      processes were blocked by either the estrogen receptor antagonist ICI 182,780 or
      by an anti-sense oligonucleotide to the estrogen receptor. Furthermore,
      incubation of the cultures with an anti-sense oligonucleotide directed against
      the insulin-like growth factor-I messenger RNA also blocked the effect of
      estradiol. In turn, the effects of insulin-like growth factor-I were blocked by
      the estrogen receptor antagonist ICI 182,780 and by the anti-sense
      oligonucleotide to the estrogen receptor. These findings suggest that estradiol
      induced activation of the estrogen receptor in developing hypothalamic cells
      requires the presence of insulin-like growth factor-I, and that both estradiol
      and insulin-like growth factor-I use the estrogen receptor as a mediator of their
      trophic effects on hypothalamic neurons.

PMID- 8865205
TI  - Change in the molecular phenotype of Schwann cells upon transplantation into the
      central nervous system: down-regulation of c-jun.
AB  - Activated Schwann cells such as those in the distal stump of a cut peripheral
      nerve, or those cultured in vitro, develop a molecular phenotype very different
      from that of quiescent Schwann cells, and express high levels of the
      transcription factor c-jun. We studied the expression of c-jun messenger RNA, by
      in situ hybridization, and Jun-like immunoreactivity of Schwann cells in segments
      of peripheral nerve, or in cell suspensions grafted into the adult rat brain.
      Schwann cells rapidly lost their Jun immuno-positivity, and down-regulated
      expression of c-jun messenger RNA once implanted into the brain, and only the
      Schwann cells contained in the portion of peripheral nerve which remained outside
      the brain maintained Jun-like immunopositivity. c-jun messenger RNA was also down
      regulated in the grafts, but more slowly than the protein; however, a
      proximodistal gradient in the level of expression of c-jun messenger RNA along
      the graft, comparable to that found for Jun immunoreactivity, was not detected.
      Schwann cells transplanted into the lesioned central nervous system promote
      regeneration of some injured central nervous system axons, but this regenerative
      response is always much more limited than peripheral nervous system regeneration.
      We suggest a correlation between the limited regeneration of central nervous
      system axons into peripheral nerve grafts and the loss of c-jun expression in
      Schwann cells following exposure to the central nervous system environment.

PMID- 8865206
TI  - Induction of differentiation of human olfactory neuroblastoma cells into odorant
      responsive cells.
AB  - Olfactory neuroblastoma is a rare malignancy of the olfactory mucosa that may be
      derived from the olfactory epithelium. To characterize this tumor, we cultured
      olfactory neuroblastoma cells in the presence or absence of growth factors
      (transforming growth factor alpha and basic fibroblast growth factor) known to
      affect olfactory tissue and assessed their responsiveness to known odorants by
      measuring changes in intracellular calcium. Untreated cells did not respond to
      odorants. Basic fibroblast growth factor treatment had cytotoxic effects, and
      treated cells did not respond to odorants. Transforming growth factor alpha
      treatment resulted in the induction of odor responsiveness in these cells. Cells
      responded to odorants at 100 nM to 100 microM concentrations and responded with
      both increases and decreases in intracellular calcium. Increases in intracellular
      calcium were mediated by a calcium influx and were reversibly blocked by
      compounds known to inhibit second messenger pathways in olfactory receptor
      neurons. The calcium responses of the olfactory neuroblastoma cells were thus
      specific to the odorants and similar to those found in olfactory receptor
      neurons. The results support the notion that olfactory neuroblastoma cells may be
      of olfactory origin and thus they can be used as a model cell line to study human
      olfaction.

PMID- 8865207
TI  - Astrocytes and extracellular matrix following intracerebral transplantation of
      embryonic ventral mesencephalon or lateral ganglionic eminence.
AB  - Transplantation of embryonic neurons to the adult mammalian central nervous
      system (CNS) offers the possibility of re-establishing neural functions lost
      after traumatic injuries or neurodegenerative disease. In the adult CNS, however,
      transplanted neurons and their growing neurites can become confined to the graft
      region, and there may also be a relative paucity of afferents innervating grafted
      neurons. Because glia may influence the development and regeneration of CNS
      neurons, the present study has characterized the distribution of astrocytes and
      developmentally regulated glycoconjugates (chondroitin-6-sulfate proteoglycan and
      tenascin) within regions of the embryonic mouse CNS used as donor tissues, and in
      and around these grafts to the adult striatum and substantia nigra. Both
      chondroitin-6-sulfate proteoglycan and tenascin are present in the embryonic
      ventral mesencephalon (in association with radial glia and their endfeet, and
      glial boundaries that cordon off the ventral mesencephalon dopamine neuron
      migratory zone) and lateral ganglionic eminence before transplantation, and they
      are conserved within grafts of these tissues to the adult mouse. Neostriatal
      grafts exhibit a heterogeneous pattern of astrocyte and extracellular matrix
      molecule distribution, unlike ventral mesencephalon grafts, which are rather
      homogeneous. There is evidence to suggest that, in addition to variation in
      astroglial/extracellular matrix immunostaining within different compartments in
      striatal grafts to either adult striatum or substantia nigra, there are also
      boundaries between these compartments that are rich in glial fibrillary acidic
      protein/extracellular matrix components. Substantia nigra grafts, with cells
      immunoreactive for tyrosine hydroxylase, are also rich in immature astroglia (RC
      2-immunopositive), and as the astroglia mature (to glial fibrillary acidic
      protein-positive) over time the expression of chondroitin-6-sulfate proteoglycan
      and tenascin is also reduced. These same extracellular matrix constituents,
      however, are only slightly up-regulated in an area of the adult host which
      surrounds the grafted tissue. Glial scar components exhibit no obvious
      differences between grafts from different sources to homotopic (e.g., striatum to
      striatum) or heterotopic (e.g., substantia nigra to striatum) sites, and likewise
      grafts of non-synaptically associated structures (e.g., cerebellum to striatum),
      needle lesions or vehicle injections all yield astroglial/extracellular matrix
      scars in the host that are indistinguishable. Studies utilizing the ROSA-26
      transgenic (beta-galactosidase-positive) mouse as a host for non-5-bromo-4-chloro
      3-indolyl-beta-d-galactopyranoside-labeled grafts indicate that the early
      astroglial/extracellular matrix response to the graft is derived from the
      surrounding host structures. Furthermore, biochemical analysis of one of the
      "boundary molecules", tenascin, from the developing ventral mesencephalon versus
      adult striatal lesions, suggests that different forms of the molecule predominate
      in the embryonic versus lesioned adult brain. Such differences in the nature and
      distribution of astroglia and developmentally regulated extracellular matrix
      molecules between donor and host regions may affect the growth and
      differentiation of transplanted neurons. The present study suggests that
      transplanted neurons and their processes may flourish within graft versus host
      regions, in part due to a confining glial scar, but also because the
      extracellular milieu within the graft site remains more representative of the
      developmental environment from which the donor neurons were obtained [Gates M.
      A., et al. (1994) Soc. Neurosci. Abstr. 20, 471].

PMID- 8865208
TI  - The potential role of dendritic cells in immune-mediated inflammatory diseases in
      the central nervous system.
AB  - Dendritic cells of the rat were studied immunohistochemically with MRC OX62
      monoclonal antibody and using electron microscopy. In normal CNS, a small number
      of OX62+ cells was detected in the choroid plexus and meninges. These cells were
      absent from other CNS and peripheral nervous system sites studied. Dendritic
      cells were also studied in two models of immune-mediated inflammatory conditions
      in the CNS. These were: acute experimental allergic encephalomyelitis and
      aberrant delayed-type hypersensitivity lesions induced as a response to heat
      killed bacillus Calmette-Guerin sequestrated behind the blood-brain barrier. In
      addition, a group of animals with a delayed-type hypersensitivity response was
      treated with dexamethasone to assess the effect of steroid treatment on T-cells
      and OX62+ cells in CNS lesions. Dendritic cells were present in many but not all
      lesions in acute experimental allergic encephalomyelitis and their numbers were
      small. In experimental allergic encephalomyelitis lesions, dendritic cells were
      found predominantly in perivascular cuffs, where they constituted approximately
      2% of the total number of major histocompatibility complex class II+ cells. Some
      of these cells were also detected in the CNS parenchyma, close to the
      perivascular cuff. In contrast, dendritic cells were present in all delayed-type
      hypersensitivity lesions studied. Their number in delayed-type hypersensitivity
      lesions was significantly higher than in experimental allergic encephalomyelitis
      lesions. Numerous OX62+ cells were found, even in three-month-old lesions.
      Electron microscopy studies revealed that these cells were often in close contact
      with lymphocytes. There was no significant change in the density of OX62+ cells,
      IL2R+ cells and OX19+ T-cells in delayed-type hypersensitivity lesions after
      seven-day treatment with dexamethasone, although there was a considerable
      reduction in the number of CD45RA+ T-cells. The high numbers of dendritic cells
      found in the delayed-type hypersensitivity lesions may be important in
      contributing to the chronicity of the response. They may also initiate autoimmune
      responses to CNS antigens uncovered during bystander tissue damage which occurs
      as a consequence of aberrant delayed-type hypersensitivity responses.

PMID- 8865209
TI  - Stable analogues of cyclic AMP but not cyclic GMP sensitize unmyelinated primary
      afferents in rat skin to heat stimulation but not to inflammatory mediators, in
      vitro.
AB  - The aim of this investigation was to evaluate the role played by cyclic
      nucleotides in the transduction of inflammatory pain and hyperalgesia.
      Unmyelinated afferents (n = 79) were exposed to stable analogues of cyclic AMP
      and cyclic GMP, to inflammatory mediators and to Methylene Blue, an inhibitor of
      guanylyl cyclase. Analogues of cyclic AMP at a concentration of 1 mM (n = 9) but
      not 10 microM (n = 16) sensitized nociceptor responses to noxious heat and
      enhanced interstimulus activity. In addition. mechanical thresholds were
      moderately, but significantly lowered after superfusion of the cyclic AMP
      analogue (1 mM). Addition of 10 microM cyclic AMP analogue to a mixture of
      excitatory inflammatory mediators (serotonin, histamine, bradykinin and
      prostaglandin E2, 10 microM each) did not further increase nociceptor activity (n
      = 15), in contrast to a previous report that cAMP sensitized bradykinin
      responses. Cyclic GMP analogues (10 microM, 1 mM) did not alter heat sensitivity
      or mechanical thresholds of polymodal C-fibres, nor did they enhance the ongoing
      activity that resulted from repeated heat stimulation. After inhibition of
      guanylyl cyclase with Methylene Blue, cyclic GMP analogues (1-10 microM) did not
      alter nociceptor responses evoked by application of the mixture of inflammatory
      mediators. The findings indicate that polymodal nociceptor sensitization and
      excitation is independent of cyclic GMP. Cyclic AMP can obviously contribute to
      the increased heat sensitivity of inflamed tissue, whereas cyclic GMP might be of
      importance in the recruitment of "silent" nociceptors.

PMID- 8865210
TI  - Pacing and hypertrophic obstructive cardiomyopathy.

PMID- 8865211
TI  - Incidence of lead system malfunction detected during implantable defibrillator
      generator replacement.
AB  - Implantable cardioverter-defibrillator (ICD) generator replacement due to a
      depleted battery is a frequently performed procedure. The frequency with which
      sensing and defibrillation system failures are identified during device
      replacement procedures has not been previously described. Therefore, the purpose
      of this study was to prospectively determine the frequency of lead system
      malfunction detected at the time of device replacement in 55 consecutive patients
      undergoing ICD generator replacement. The mean age of the patients was 63 +/- 10
      years and 40 of them were men. Forty-nine patients had an epicardial lead system,
      and six patients had a nonthoracotomy lead system. Four [7%] of these 55 patients
      were noted to have previously undetected lead system failure, either sensing (n =
      3) or defibrillation (n = 1), necessitating system revision. The lead systems
      that failed were 40 +/- 6 months old (33-49 months). In summary, during ICD
      generator replacement, previously undetected problems with sensing or
      defibrillation may be identified in approximately 10% of patients. Therefore, a
      comprehensive evaluation of the sensing and the defibrillation functions should
      be an essential component of the ICD generator replacement procedure.

PMID- 8865212
TI  - A comparison of quality-of-life in patients with dual chamber pacemakers and
      individually programmed atrioventricular delays.
AB  - Dual chamber pacemakers are increasingly implanted to achieve optimal
      hemodynamics by AV synchrony, but the effect of AV delay programming on the
      patient's quality-of-life has been less well studied. The influence of an
      individually programmed AV delay between 100 and 250 ms on quality-of-life was
      investigated in a randomized, double-blind crossover study of 13 patients (69 +/-
      10 years of age) with dual chamber pacemakers implanted because of high degree AV
      block. During radionuclide ventriculography at rest, the "optimal AV delay" with
      the maximal left ventricular ejection fraction and the "most unfavorable AV
      delay" with the least ejection fraction were determined. The ejection fraction at
      rest with the "optimal AV delay" was 51% +/- 10%, and with the "most unfavorable
      AV delay," 44% +/- 11% (P < 0.0001). The optimal AV delay determined by
      radionuclide ventriculography correlated well with the optimal AV delay
      determined by Doppler echocardiography using flow velocity integrals (r = 0.78, P
      < 0.0016). Each patient was assigned in random order to either AV delay during a
      2-week period and then the pacing mode was switched for another 2-week period. At
      the end of each period, patients were assessed by a functional status
      questionnaire to assess physical capability and two further questionnaires to
      quantify cardiovascular symptoms or self-perceived health. There were no
      differences in the two AV delays regarding the patient's perceived physical
      capability and specific symptoms. The patient's total judgment was identical to
      the optimal AV delay (score 36% +/- 19%) and the most unfavorable AV delay (33%
      +/- 21%). Thus, in patients with a dual chamber pacemaker, an individually
      programmed AV delay affects left ventricular function at rest, but has no
      influence on quality-of-life. The determination of the flow velocity integral by
      Doppler echocardiography is a simple and reliable method to optimize the AV delay
      if necessary.

PMID- 8865213
TI  - Electrophysiological characteristics of bipolar membrane carbon leads with and
      without steroid elution compared with a conventional carbon and a steroid-eluting
      platinum lead.
AB  - In a controlled study, the following four bipolar leads with passive fixation
      were implanted in 46 patients with the Siemens-Multilog-VVI or Sensolog-VVIR
      pacemakers: membrane covered activated porous carbon with steroid elution
      (Siemens 1402 T, 11 patients) and without (Siemens 1403 T, 15 patients);
      activated carbon (Siemens 1010 T, 10 patients); and platinum with steroid elution
      (Medtronic Cap-Sure 5026, 10 patients). Stimulation threshold (STH) (assessed by
      a vario-test), impedance (IMP), and the intracardial R wave potential (IRW) (both
      gauged by a telemetric method) were measured 1, 5, and 10 days as well as 3 and 6
      months after implantation during unipolar and bipolar stimulation, chronaxie
      rheobase product (CRP) and energy consumption (EC) were systematically
      determined. Differing insignificantly at the first day after implantation, STH is
      significantly lower for the 1402 T and CapSure 5026 leads at the tenth day.
      However, the 1402 T lead shows a significant increase of STH in the follow-up, in
      contrast to the other leads. The lowest chronic STH was found in the CapSure 5026
      lead (CRP is significantly lower in all other leads, too). IMP is significantly
      lower in the CapSure 5026 lead compared to 1010 T lead. EC does not differ
      significantly during chronic stimulation in spite of the best possible
      programming of pulse amplitude and duration. No significant changes of IRW were
      observed. Unipolar versus bipolar stimulation shows significantly lower STH, CRP,
      and IMP, differences of EC and IRW were insignificant. In conclusion, the
      addition of steroid in membrane covered carbon leads protracts the increase of
      STH, but does not prevent it. The CapSure 5026 lead shows advantageous
      stimulation characteristics, but energy consumption is not significantly reduced
      because of low impedance and impossibility of programming an appropriate low
      output in Multilog pacemakers.

PMID- 8865214
TI  - Transient entrainment: the evolution of a medical concept from description to
      prescription.
AB  - Entrainment is a phenomenon that has come to have considerable utility in cardiac
      electro-physiology diagnosis and treatment; specifically, to identify a zone of
      slow conduction in a reentrant circuit, a zone hypothetically vulnerable to
      intervention from the application of RF energy. The observation of entrainment
      has gone through an evolutionary sequence in the literature, from the initial
      simple observations of the phenomenon to the present stage of relatively fixed
      criteria of identification. This article follows the evolution of the specific
      features of the criteria of entrainment to their current crystallization into
      features that are suggested to prescribe sites for attempted ablation. This
      examination of the evolutionary course of the development of the conception of
      entrainment is of interest not only to cardiac electrophysiology, but also to
      philosophers of science, by illustrating how scientists emphasize and develop
      certain observations with the ultimate aim of applying the observations for
      successful intervention in pathological entities.

PMID- 8865215
TI  - A conceptual basis for pacing waveforms.
AB  - A model is developed that allows evaluation of the pacing efficacy of different
      stimulus waveforms. It treats the heart as having a first order time constant and
      enables ready visualization of the time course of the effective voltage within
      the heart. For pacemakers, where the stimulus pulse is produced by the discharge
      of a capacitor, the voltage within the heart rapidly rises to a peak and then
      more slowly decays to zero. The time interval at which the peak occurs defines
      the optimal duration, i.e., the shortest duration with minimal pacing voltage.
      Characteristics are developed that show the changes in optimal duration and
      pacing threshold for changes in the pacemaker's output capacitor and for
      differences in lead impedance and time constant of the heart.

PMID- 8865216
TI  - A conceptual basis for defibrillation waveforms.
AB  - A model is developed for defibrillation that treats the heart as a first order
      time constant. Such a model allows ready evaluation of different monophasic
      waveforms. For implantable devices where the voltage is provided by the discharge
      of a capacitor, it can be seen that the effective voltage within the heart rises
      rapidly to a peak and then decays to zero. The time interval at which this peak
      occurs is defined as the optimal duration, and there is no advantage in extending
      the pulse beyond this point. Characteristics are presented that show how the time
      course of this voltage within the heart changes with different device capacitors
      and load impedances. The effect of different heart time constant are also
      examined. For biphasic waveforms, a contour plot of threshold voltage is
      presented with phase 1 and phase 2 durations on the two axes. It is seen that
      there is a region of reliable low threshold defibrillation from 3.5/1.5 ms to 9/6
      ms.

PMID- 8865217
TI  - A comparison of unipolar and bipolar electrodes during cardiac mapping studies.
AB  - Controversy exists as to whether the unipolar or bipolar electrode configuration
      is superior in detecting local activations during cardiac mapping studies.
      However, the strengths and weaknesses of each mode suggest that they may provide
      complementary information. To examine the relative merits of unipolar and bipolar
      electrode configurations, recordings by each were simultaneously acquired during
      episodes of ventricular tachycardia in eight consecutive patients undergoing map
      guided arrhythmia surgery. Unipolar electrograms were classified as either
      unambiguous or ambiguous according to whether or not they were polyphasic in
      nature. The activation times from the unambiguous electrograms were compared with
      activation times from the corresponding bipolar signals where local activation
      was measured both at the signal's peak amplitude (BI-PK), and at the point at
      which the waveform's first major, rapid transient crossed baseline (BI-TRN).
      Occurrences of discrete diastolic activations were also quantified from the
      unipolar and bipolar tracings. From a total of 415 unipolar electrograms, 301
      unambiguous signals were identified as suitable for comparison with the bipolar
      signals. Both BI-PK and BI-TRN criteria for the determination of local activation
      were highly correlated with and not significantly different from the local
      activation from the unipolar electrogram. From 85 ambiguous unipolar
      electrograms, it was possible to determine local activation from the
      corresponding bipolar signal in 33% of the occurrences. From the eight patients,
      64 diastolic potentials were recorded of which 42 were seen only in bipolar mode,
      7 in only unipolar mode, and 15 were evident in both tracings. The prevalence of
      diastolic potentials was significantly greater in recordings made using bipolar
      mode. The results demonstrate that complementary information regarding local
      activations and diastolic potentials can be derived from unipolar and bipolar
      recordings and suggest that both electrode configurations should be used in
      multichannel cardiac mapping systems.

PMID- 8865218
TI  - Electrostimulated cardiomyoplasty: from experimental to clinical studies.
AB  - Cardiomyoplasty is a method for managing patients with dilated cardiomyopathy. We
      evaluated the means of carbon fiber electrode stimulation of the nerve to the
      latissimus dorsi muscle (LDM) in dogs to increase skeletal muscle contractility.
      Histochemical examination of biopsies of muscle electrically conditioned by a
      single pulse stimulator via the thoracodorsal nerve demonstrated transformation
      of muscle into fatigue resistant slow fibers without damage to muscle or nerve
      tissue. Canine experiments confirmed that carbon fibers are one of the best
      electrodes for chronic LDM stimulation. Between 1988 and 1992, we operated on ten
      patients, New York Heart Association (NYHA) Class III (4 patients) and Class IV
      (6 patients), with a mean left ventricular ejection fraction (LVEF) of 23%. The
      indications for cardiomyoplasty were idiopathic (7 patients) and ischemic (3
      patients) cardiomyopathy refractory to maximum medical therapy. The operative
      procedure was performed via median sternotomy (5 patients) and left thoracotomy
      (5 patients). There was one operative mortality and two additional deaths during
      the late follow-up period. The mean postoperative LVEF increased to 27%.
      Functional class, quality-of-life, and ventricular performance were improved
      after cardiomyoplasty. Two of the surviving patients are in NYHA Class I, four in
      Class II, and one in Class III.

PMID- 8865219
TI  - Improved sensing signals after endocardial defibrillation with a redesigned
      integrated sense pace defibrillation lead.
AB  - Adequate sensing is a basic requirement for appropriate therapy with ICDs.
      Integrated sense pace defibrillation leads, which facilitate ICD implantation,
      show a close proximity of sensing and defibrillation electrodes that might affect
      the sensing signal amplitude by the high currents of internal defibrillation. In
      99 patients, we retrospectively examined two integrated sense pace defibrillation
      leads, either both with a distance of 6 mm between the tip of the lead (sensing
      cathode) and the right ventricular defibrillation electrode (sensing anode) or
      one with a distance of 12 mm. Three seconds after a shock of 20 J, mean sensing
      signal amplitude during sinus rhythm (SR) decreased from 10.5 +/- 4.3 mV to 5.1
      +/- 3.7 mV (P < 0.001) for the 6-mm lead, but showed no significant decrease for
      the 12-mm lead. The degree of signal reduction was inversely related to the time
      passed since defibrillation. Significant differences in reduction of sensing
      signal amplitude concerning monophasic and biphasic shocks could not be observed.
      Mean sensing signal amplitude of VF after shocks that failed to terminate it
      decreased in the same order as during SR (from 8.3 +/- 4.1 mV to 4.1 +/- 3.2 mV),
      but resulted in no failure of redetection during ongoing VF. DFTs did not differ
      for the 6-mm and the 12-mm lead. In conclusion, close proximity of the right
      ventricular defibrillation coil to the sensing tip of an integrated sense pace
      defibrillation lead causes energy and time related reduction in sensing signal
      amplitude after defibrillation, and might cause undersensing in the postshock
      period. A new lead design with a more proximal position of the right ventricular
      defibrillation coil avoids these problems without impairing DFTs.

PMID- 8865220
TI  - Pacemaker follow-up with prolonged intervals in the stable period 1 to 5 years
      postimplant.
AB  - This pilot study focuses on pacemaker follow-up in the technically stable period
      1-5 years after a pacemaker implantation. Two hundred and thirty selected
      patients with single chamber pacemakers (215 VVI, 15 AAI) had their follow-up
      intervals prolonged to 2-4 years in this period. Sixty-six patients fulfilled the
      study period uneventfully and 21 are still pending. Sixty-nine patients had
      unscheduled visits to the pacemaker clinic. Of these, 7 were reoperated (1 for
      exit block, 4 had pocket erosions, and 2 were upgraded to DDD). Nine were
      reprogrammed (1 for sensing failure, 1 had the pulse duration increased, and in 7
      the pacing rate was changed). Seventy-four patients died. In 63, the cause of
      death is known not to be pacemaker related. Six died suddenly, and in five cases,
      the cause of death is unknown. This study indicates that frequent follow-up
      visits may be omitted in this period in selected patients with single chamber
      pacemakers. A prerequisite is that the patients are registered at a pacemaker
      clinic and have easy access to the physician whenever they suspect pacemaker
      related problems.

PMID- 8865221
TI  - Improved recovery of high frequency P wave energy by selective P wave averaging.
AB  - Most signal averaging processes used for cardiac signals align successive
      waveforms using a template matching process. In addition to achieving accurate
      temporal alignment of the signals, this operation must also ensure that the
      signal average comprises signals of the same morphology. For P wave signal
      averaging, systems designed for QRS complex averaging are often used, with the
      template acquisition window shifted to include the P wave. Theoretically, with
      this technique, variations in P wave morphology could reduce the high frequency
      content of the signal. We tested this hypothesis by comparing the performance of
      a selective P wave averaging system with a conventional system, based on template
      matching by cross-correlation over a fixed acquisition window, on identical P
      wave recordings from 15 subjects. The selective system identifies variations in P
      wave morphology and generates up to five candidate templates for averaging.
      Subsequently, the most frequently matched template over a 100-beat sample is used
      for averaging. Only P waves with the same morphology as this template are
      averaged. Selective averaging mainly increased the measured high frequency P wave
      energy, without affecting P wave duration after high pass filtering at 40 Hz,
      (Duration: 157(4)ms selective vs 155(4) nonselective. Energy 80-150 Hz:
      1.77(0.28), microV2.s selective vs 1.61(0.3) microV2.s non selective, P < 0.01).
      These observations confirm that nonselective P wave averaging can reduce apparent
      P wave energy, especially at high frequency. Before meaningful studies of the
      value of frequency domain analysis of the P wave can be performed, it is
      important that signal averaging systems of sufficient fidelity are utilized.

PMID- 8865223
TI  - A computer database for a cardiology clinic.

PMID- 8865222
TI  - A comparative analysis of signal processing methods for motion-based rate
      responsive pacing.
AB  - Pacemakers that augment heart rate (HR) by sensing body motion have been the most
      frequently prescribed rate responsive pacemakers. Many comparisons between motion
      based rate responsive pacemaker models have been published. However, conclusions
      regarding specific signal processing methods used for rate response (e.g.,
      filters and algorithms) can be affected by device-specific features. To
      objectively compare commonly used motion sensing filters and algorithms,
      acceleration and ECG signals were recorded from 16 normal subjects performing
      exercise and daily living activities. Acceleration signals were filtered (1-4 or
      15-Hz band-pass), then processed using threshold crossing (TC) or integration
      (IN) algorithms creating four filter/algorithm combinations. Data were converted
      to an acceleration indicated rate and compared to intrinsic HR using root mean
      square difference (RMSd) and signed RMSd. Overall, the filters and algorithms
      performed similarly for most activities. The only differences between filters
      were for walking at an increasing grade (1-4 Hz superior to 15-Hz) and for
      rocking in a chair (15-Hz superior to 1-4 Hz). The only differences between
      algorithms were for bicycling (TC superior to IN), walking at an increasing grade
      (IN superior to TC), and holding a drill (IN superior to TC). Performance of the
      four filter/algorithm combinations was also similar over most activities. The 1
      4/IN (filter [Hz]/algorithm) combination performed best for walking at a grade,
      while the 15/TC combination was best for bicycling. However, the 15/TC
      combination tended to be most sensitive to higher frequency artifact, such as
      automobile driving, downstairs walking, and hand drilling. Chair rocking artifact
      was highest for 1-4/IN. The RMSd for bicycling and upstairs walking were large
      for all combinations, reflecting the nonphysiological nature of the sensor. The 1
      4/TC combination demonstrated the least intersubject variability, was the only
      filter/algorithm combination insensitive to changes in footwear, and gave similar
      RMSd over a large range of amplitude thresholds for most activities. In
      conclusion, based on overall error performance, the preferred filter/algorithm
      combination depended upon the type of activity.

PMID- 8865224
TI  - Pacing and electrophysiology in Australia.

PMID- 8865225
TI  - Diagnosis of retrograde ventriculoatrial conduction by left atrial appendage
      Doppler flow analysis.
AB  - We report a case of pacemaker syndrome where the diagnosis of retrograde
      ventriculoatrial conduction was made by Doppler analysis of left atrial appendage
      flow. Doppler analysis of left atrial appendage flow provides another noninvasive
      parameter to diagnose retrograde ventriculoatrial conduction.

PMID- 8865226
TI  - Implantable cardioverter defibrillator therapy in a patient with the idiopathic
      long QT syndrome.
AB  - The idiopathic long QT syndrome (LQTS) carries a high mortality in untreated
      patients. Administration of beta-receptor antagonists is considered the treatment
      of choice. Data concerning the usefulness of implantable cardioverter
      defibrillator (ICD) therapy in this condition are sparse. We report on a 29-year
      old female with LQTS who was treated with propranolol, but also underwent
      implantation of an ICD as a fail-safe therapy. During the next 17 months, the
      patient was asymptomatic. However, after skipping her propranolol for 3 days, she
      had several syncopal spells with concomitant device therapy. ICD interrogation
      revealed a total of 55 nonsustained runs of ventricular tachycardia and 16
      sustained episodes that were correctly identified by the device and respectively
      terminated by the first shock. This case report demonstrates that in selected
      patients with the LQTS, using ICD therapy as a fail-safe treatment may be life
      saving, particularly when compliance to medical therapy is uncertain.

PMID- 8865227
TI  - Sudden death as a presenting symptom of hypertrophic cardiomyopathy: treatment
      with an implantable cardioverter defibrillator.
AB  - Aborted sudden death as the presenting manifestation of hypertrophic
      cardiomyopathy in a 14-year-old child is reported. Documented ventricular
      fibrillation was the cause of cardiac arrest. No ventricular arrhythmia was
      induced during programmed electrical stimulation. An implantable cardioverter
      defibrillator was indicated. As the patient had a family history of myocardial
      disease, he had undergone a cardiovascular evaluation 4 years before the major
      event, and was found normal. It is suggested that normal physical examination,
      ECG, echocardiogram should not rule out the diagnosis of hypertrophic
      cardiomyopathy when a family history is present. Left ventricular hypertrophy may
      develop during childhood in patients with hypertrophic cardiomyopathy.

PMID- 8865228
TI  - Lead explantation late after atrial perforation.
AB  - This report describes the case of a patient in whom atrial perforation with
      penetration of the thoracic wall was diagnosed 2 years after the implantation of
      an Accufix lead. Despite this complication, atrial detection in the bipolar mode
      and ventricular pacing were normal. Digital fluoroscopy detected a fracture with
      extrusion of a short segment of the retention wire. The rupture of the retention
      wire might have been the result, but was not the cause of the perforation.

PMID- 8865229
TI  - Optimization of defibrillation pulses.

PMID- 8865230
TI  - Late atrioventricular (AV) block and permanent pacemaker implantation after
      orthotopic cardiac transplantation.

PMID- 8865231
TI  - Linkage of Gitelman syndrome to the thiazide-sensitive sodium-chloride
      cotransporter gene with identification of mutations in Dutch families.
AB  - Gitelman syndrome is a mostly autosomal recessive disorder affecting the renal
      tubular function associated with hypokalemia and hypomagnesemia. Functional
      studies point to a defect in the distal renal tubule in the thiazide-sensitive,
      electroneutral sodium-chloride co-transporter (TSC). Based upon the localization
      of a 2.6 cDNA encoding the human TSC to chromosome 16q13, polymorphic markers
      spanning the region from 16p12 to 16q21 were tested for linkage to the Gitelman
      syndrome locus in three Dutch families with autosomal recessive inheritance of
      this disorder. Using two-point linkage analysis, a maximum LOD score (Zmax of
      4.49 (at theta = 0.00) was found for the marker D16S408. One crucial
      recombination event places the Gitelman syndrome locus distal to D16S419 at 16q12
      13. Subsequently we have tested our group of Gitelman patients for mutations in
      the human TSC gene. Two mutations were identified in three Gitelman families. Our
      study confirms that the human TSC gene is involved in Gitelman syndrome. Patients
      from three Gitelman families reveal two identical human TSC mutations, suggesting
      these families share a common ancestor.

PMID- 8865232
TI  - Day care renal biopsy.
AB  - Over the 6 years 1989-1994, 384 percutaneous renal biopsies were performed, 329
      on native and 55 on transplanted kidneys. Biopsy was undertaken on a day care
      basis in 304 instances (79.2%). Failure to obtain 5 or more glomeruli was
      experienced in 23 (6.0%) of the 304 day care biopsies. There were no significant
      differences in technical failure rates between day care patients and inpatients,
      local analgesia and general anaesthetic, or native and transplanted kidneys, but
      a higher rate was observed in biopsies performed unaided by trainees than by
      experienced operators (P = 0.002). Six patients were detained overnight for minor
      complications and a seventh for unrelated reasons. Two patients discharged on the
      day of biopsy despite gross haematuria were readmitted 8-10 days later with
      secondary haemorrhage. The complication rate of 2.6% compares favourably with
      published data. Few paediatric renal units currently perform day care renal
      biopsy, and we recommend its wider acceptance.

PMID- 8865233
TI  - Renal biopsy in the 1990s.

PMID- 8865234
TI  - A case of neonatal Bartter's syndrome.
AB  - We describe a child with a neonatal presentation of Bartter's syndrome. Unlike
      infants previously described with a similar clinical presentation, the urinary
      excretion rate of prostaglandin E2 in this child was similar to normal children
      and Tamm-Horsfall protein was distributed normally in the thick ascending limb of
      the loop of Henle. The child failed to respond to indomethacin alone, but thrived
      after the addition of the angiotensin converting enzyme inhibitor, captopril.

PMID- 8865235
TI  - Variants of Bartter's syndrome.

PMID- 8865236
TI  - The 1994 annual report of the North American Pediatric Renal Transplant
      Cooperative Study.
AB  - The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) is a
      research effort that was organized and initiated in 1987. The following
      manuscript is the 1994 NAPRTCS annual report which has summarized data that has
      been voluntarily contributed by 83 centers. The report includes data on 3,183
      patients who have undergone a total of 3,445 renal transplants between 1 January
      1987 and 18 February 1994 when the data set was closed. The report also contains
      data on 1,611 independent courses of dialysis which were initiated between 1
      January 1992 and 18 February 1994. This report is meant to update the previous
      NAPRTCS annual reports as well as demonstrate how the NAPRTCS database has
      changed clinical practice since its inception. There have been 855 graft failures
      among the 3,438 transplants. Due to the maturing of the database, chronic
      rejection now accounts for 34% of graft failures which have occurred over the
      last year. Graft failure was increased in recipients if the recipients were < 2
      years of age, of the black race, or had received five or more prior transfusions.
      Early treatment with antithymocyte globulin/antilymphocyte globulin/OKT3 was
      associated with increased graft survival. Catch-up growth post transplant was
      only seen in the youngest patients (< 6 years of age). Those patients > 6 years
      did not have catch-up growth post transplant. Overall graft survival has improved
      markedly since the inception of this study. The dialysis database is just
      maturing and the data confirm that growth on dialysis continues to be very poor.
      The 1994 annual report of NAPRTCS extends previous findings of this valuable
      database. It is gratifying to know that early findings of NAPRTCS have led to
      changes in therapy which have led to improvement in the care of these very
      special children.

PMID- 8865237
TI  - Urinary inhibitors of crystallization in hypercalciuric children with hematuria
      and nephrolithiasis.
AB  - Urinary inhibitors are suggested to play a significant role in reducing
      crystallization in calcium (Ca) stone former and idiopathic hypercalciuria (IH).
      Urinary inhibitors such as magnesium (Mg), citrate, and glycosaminoglycans (GAGs)
      were evaluated, as well as urinary Ca and creatinine (Cr), in IH children with
      nephrolithiasis (LIT) or with hematuria plus IH (HEM) and were compared with a
      control group. The mean 24-h urinary excretion of Mg was similar in all groups.
      However, the urine Ca/Mg ratio was significantly increased (P < 0.005) in LIT and
      HEM groups. A higher mean value for GAGs and citrate was found in the HEM group,
      but a very low level of GAGs (less than 60% of the normal value) and citrate
      (less than 30% of the normal value) was found in the LIT group. These data
      suggest that, despite a high urinary Ca excretion (3.6 +/- 0.1 mg/kg per day) in
      the HEM group, elevated urinary GAGs (32.0 +/- 1.0 mg/g Cr) and a normal urinary
      citrate (428.7 +/- 62.3 mg/24 h) excretion may prevent Ca crystallization and
      thus renal stones. In contrast, in the LIT group low urinary GAG (10.3 +/- 0.9
      mg/g Cr) and citrate (235.2 +/- 52.3 mg/24 h) excretion may precipitate stone
      formation in the presence of a high urinary Ca excretion. Thus, it is reasonable
      to suggest that patients with hematuria and IH may not develop overt renal stone
      due to the presence of normal levels of renal stone inhibitors.

PMID- 8865238
TI  - Severe pseudohypoaldosteronism in a pair of twins not associated with hydramnios.
AB  - A pair of non-identical twins with severe pseudohypoaldosteronism (PHA) were
      followed over a period of 4 years. The diagnosis was based on dehydration,
      hyponatremia, hyperkalemia, high urine sodium/potassium ratios, and high serum
      concentrations of aldosterone and renin. Sweat and saliva electrolyte
      concentrations were high, suggesting multifocal target-organ unresponsiveness to
      mineralocorticoids. No hydramnios was observed during pregnancy. Despite
      continuous treatment with sodium chloride and sodium bicarbonate (< or = 20
      g/day) and cation exchange resin (Kayexalate, sodium polystyrene sulfonate, < or
      = 4 g/kg per day), the children had repeated episodes of dehydration,
      hyponatremia, and hyperkalemia. Growth velocity was normal in both twins. Catch
      up growth was observed following infancy in the first twin. Normalization of
      plasma aldosterone, electrolytes, and renin concentrations was achieved at the
      age of 9 months.

PMID- 8865239
TI  - Nephrocalcinosis in a patient with primary hyperoxaluria type 2.
AB  - Although nephrocalcinosis is a classical finding in primary hyperoxaluria type 1
      (PH 1) associated with a poor renal survival it is exceptional in patients with
      PH type 2 (PH 2), characterized by a more favorable outcome. We describe an 8
      month-old girl who suffered from recurrent urinary tract infections. Imaging
      studies revealed a profound corticomedullary nephrocalcinosis with no evidence of
      calculi. Urinary oxalate and D-glycerate excretion were massively elevated, while
      urinary glycolate or glyoxylate could not be detected, confirming the diagnosis
      of PH 2. Although the nephrocalcinosis progressed radiologically, renal function
      remained stable for over 2 years. Only further follow-up will show whether the
      associated nephrocalcinosis worsens the prognosis of our patient and of PH 2 in
      general.

PMID- 8865240
TI  - The neutrophil oxidative burst in diarrhoea-associated haemolytic uraemic
      syndrome.
AB  - Neutrophil-mediated tissue damage has been implicated in the pathogenesis of
      diarrhoea-associated haemolytic uraemic syndrome (D+ HUS). This study evaluates
      priming and activation of the neutrophil oxidative burst in D+ HUS using
      chemiluminescent techniques. Peripheral blood neutrophils from 11 children with
      acute D+ HUS were examined. No difference was found in the oxidative burst of
      neutrophils from patients and controls. Serum elastase levels were measured in 8
      patients and found to be significantly elevated. Although elastase results
      suggest neutrophil activation, chemiluminescence studies do not confirm this in
      the peripheral blood neutrophil. This does not support a significant role for
      circulating agents in priming and activating the peripheral blood neutrophil.

PMID- 8865241
TI  - Tamm-Horsfall protein as a marker of tubular maturation.
AB  - Tamm-Horsfall protein (THP), a glycoprotein with a molecular weight of 95
      kilodaltons, is produced and secreted in the ascending loop of Henle. To evaluate
      the measurement of THP in the assessment of fetal renal development and function,
      we stained fetal kidney sections for THP and measured THP concentrations in 129
      amniotic fluid samples from healthy pregnancies, together with other parameters
      such as transferrin, albumin, alpha 1- and beta 2-microglobulin. After the 16th
      week of gestation THP could be detected immunohistochemically in the distal
      tubular cells, but was not consistently detected by sandwich enzyme immunoassay
      until after the 20th week of gestation (detection limit 50 ng/ml). Between the
      15th and 19th week of gestation THP was only detected occasionally, but after the
      20th week of gestation the concentration increased significantly reaching levels
      of 0.4-4 mg/l at term. The THP concentration was lower in samples taken directly
      before birth than in the corresponding first urine after birth, indicating that
      THP is produced from the fetal kidney only and does not pass the placental
      barrier. This pattern was different from other proteins studied. Transferrin and
      albumin were significantly lower in the first urine voided, microglobulins
      remained unchanged, and the creatinine concentration increased. This indicates
      that maternal to fetal exchange or transport is likely for most of the other
      proteins. Measurement of THP concentrations, in addition to other proteins in the
      amniotic fluid, can improve fetal renal assessment, but because the range of THP
      concentrations is wide accurate predictions are still not possible.

PMID- 8865242
TI  - Interleukin-1 alpha and interleukin-6 in the urine, kidney, and bladder of mice
      inoculated with Escherichia coli.
AB  - After bladder inoculation of mice using the pyelonephritogenic Escherichia coli
      strain DS17, urinary interleukin-1 alpha (IL-1 alpha) peaked at 0.5 h post
      infection (mean 233 pg/ml), interleukin-6 (IL-6) at 2 h (mean 572 pg/ml), and
      leukocyturia at 4 h, all three persisting for more than 24 h. In the kidneys IL-1
      alpha peaked at 2 h, persisted over 24 h (mean 900-1,000 pg/ml), and decreased
      over 2-6 days post inoculation to a mean value of 208 pg/ml. Control kidneys
      showed low IL-1 alpha values. IL-6 in the kidneys peaked at 5 h (mean 9,999
      pg/ml) but normalized, i.e., similar to control kidneys, by 48 h (mean 105
      pg/ml). A similar cytokine response, but with tenfold lower levels, was found in
      the bladder tissue. The isogenic P-negative E. coli mutant DS178 elicited lower
      IL-6 in the kidneys at 5 h, but persisted in higher numbers in the kidneys at 6
      days. Bacterial counts and cytokine levels correlated both in the kidneys and in
      bladder tissue, (r = 0.50-0.76, P < 0.001). Characterization of the immune
      response gives a better understanding of the relative importance of different
      bacterial characteristics for the local inflammatory process and is needed for
      studies of its pharmacological down-regulation.

PMID- 8865243
TI  - Functional renal maturation in rat neonates after prenatal exposure to
      furosemide.
AB  - We investigated the pattern of functional renal maturation and electrolyte
      handling on postnatal day 1, (PD1), day 5 (PD5), and day 12 (PD12) in rat
      neonates, after mothers were given furosemide during pregnancy. The drug was
      administered (75 mg/kg per day i.p.) on day 7-11 (organogenesis) and 14-18
      (nephrogenesis) of gestation. On PD1 and PD5, there was a disturbance of the
      urinary concentrating ability with a hyperdiuresis and an over-stimulated ionic
      exchange, mainly the distal sodium reabsorption. From PD1 to PD12, a progressive
      functional recovery in electrolyte handling appeared. However, on PD12, when
      nephrogenesis was achieved, the renal concentrating defect remained. We discuss
      the possibility of a drug-induced delay in the development of the loop of Henle,
      leading to functional and morphological adaptations of already developed parts of
      the nephron.

PMID- 8865244
TI  - Glomerular basement membrane outpockets and glomerular growth in the postnatal
      development of the rat kidney.
AB  - Distribution of glomerular basement membrane (GBM) outpockets and dimensional
      growth of glomeruli were studied in the maturing stage of rat glomeruli after
      completion of nephrogenesis. We observed the postnatal rat glomeruli from 5 to 60
      days of age by transmission electron microscopy and estimated the structural
      development of glomeruli by computerized morphometry. On day 5, the GBM was
      double in structure, possessing an epithelial and endothelial lamina densa. After
      day 10, the lamina densa of the GBM was single and sent branches toward the
      epithelial side making outpockets. There is no change in the distributional
      pattern of the outpockets, at least from day 10 to day 60, although they
      decreased considerably in number between days 20 and 40. They were found almost
      exclusively on the peripheral surface of the glomerulus. The rat glomeruli
      increased in volume constantly in this period, and the capillary volume increased
      more significantly than the mesangial volume. The GBM surface area increased in
      parallel with the glomerular tuft volume. The growing mode of capillaries was
      different before and after day 40; namely before day 40 elongation was
      predominant, whereas after day 40 widening was more pronounced. These results
      indicate that if the outpockets are the other site of GBM assembly after fusion
      of double basement membranes, the GBM must be redistributed from the peripheral
      to the paramesangial site to enable elongation and branch formation of
      capillaries during the growth of glomeruli.

PMID- 8865245
TI  - Characterization of insulin-like growth factors and their binding proteins in
      peritoneal dialysate.
AB  - Serum insulin-like growth factors (IGFs), which circulate bound to specific IGF
      binding proteins (IGFBPs), must exit the intravascular space before acting on
      target tissues. Little is known about the nature of IGF/IGFBPs in extravascular
      fluids of patients with chronic renal failure (CRF). Peritoneal dialysate (PD)
      was studied since, after a short incubation, PD contains proteins which have
      entered an extravascular space; thus, IGF/IGFBP forms in PD are more likely than
      serum forms to interact with target tissues. IGF-I and IGF-II, and IGFBPs 1-4,
      were readily identified by specific immunoassays and/or 125iodine-IGF ligand
      blotting of simultaneously obtained PD and serum samples from seven CRF children;
      IGFBP-3 was a major IGFBP in PD as in serum. Where quantitated, IGF and IGFBP
      levels in PD were approximately 10% of serum concentrations. After separation of
      PD and serum by size-exclusion chromatography, serum had more IGFBP-3 in 150
      kilodalton (kDa) than 35-kDa fractions, while PD had far less IGFBP-3 in 150-kDa
      than 35-kDa fractions. Immunoblot studies revealed a major 29-kDa IGFBP-3
      fragment, in addition to intact 41- and 38-kDa IGFBP-3 forms, in PD and CRF
      serum; the 29-kDa form predominated in the 35-kDa PD fractions. These data
      suggest that the 29-kDa fragment is the IGFBP-3 form most likely to modulate IGF
      effects on target tissues of CRF individuals.

PMID- 8865247
TI  - End-stage renal disease of the Tunisian child: epidemiology, etiologies, and
      outcome.
AB  - From December 1989 to December 1993, 90 children under 15 years were admitted to
      our department for end-stage renal disease; 9 children were less than 5 years and
      28 were aged between 5 and 10 years. The sex ratio (M/F) of the children was 2.1.
      The estimated incidence of pediatric end-stage renal disease in Tunisia is 7 new
      cases per year and per million child population under 15 years. The chief
      etiologies of end-stage renal disease are glomerulonephritis (19%), hereditary
      nephropathies (29%), and malformative uropathies (13%); 26% of the end-stage
      renal diseases are of unknown etiologies. Our findings, compared with the
      European data, show a particularly high frequency of primary hyperoxaluria
      (13.5%) and an unusual proportion of male subjects.

PMID- 8865246
TI  - Impact of age on renal graft survival in children after the first rejection
      episode.
AB  - Infants are thought to be more immunoreactive and at a greater risk for
      developing irreversible rejection compared with older children. We investigated
      this by analyzing patient and graft survival rates, incidence of acute rejection,
      reversibility of acute rejection, development of a subsequent acute rejection,
      and incidence of graft loss due to rejection in 154 children (< 18 years of age)
      after primary renal transplantation. Most patients (n = 139) were treated with
      quadruple immunosuppression (antibody, azathioprine, prednisone, cyclosporine).
      Treatment of the first acute rejection episode (ARE) consisted of antibody and
      increased prednisone (68%) or increased prednisone alone (30%), and was not
      significantly different between the age groups. Transplants were from living
      donors (LRD) in 80% of cases. Patients were followed for at least 1 year (mean 58
      +/- 30 months); 68% (105/154) of recipients experienced 1 or more ARE. The
      incidence of ARE was significantly lower in patients < 2 years of age (45%)
      compared with patients 2-5 (76%, P = 0.01), 6-12 (78%, P = 0.005), and 13-17
      (76%, P = 0.009) years of age. There was no significant difference in the 1-, 2-
      and 5-year patient or graft survival rates, the development of a subsequent acute
      rejection, or the incidence of graft loss due to acute rejection when analyzed by
      age group. These data suggest that the impact of an ARE is similar for younger
      and older children in our population receiving predominantly LRD transplants and
      quadruple immuno-suppression.

PMID- 8865248
TI  - Effects of growth hormone on insulin-like growth factors and binding proteins
      before and after renal transplantation.
AB  - Three short children with severe chronic renal failure were treated with
      recombinant human growth hormone (rhGH) for 2 years. Each received a transplant
      in the 2nd year. Serum collected before and during rhGH therapy was analysed
      retrospectively by Western ligand blot and immunoblotting techniques. In
      addition, radioimmuno-assays for insulin-like growth factor-I (IGF-I), IGF
      binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were
      performed. IGFBPs in serum, detected by Western ligand blot, were identified as
      IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each
      child rose approximately fourfold with rhGH before transplantation and
      subsequently remained elevated. IGFBP-3 levels rose to double the pretreatment
      value, but dropped to normal levels following transplantation, while ALS rose
      with rhGH treatment and remained increased after transplantation. IGFBP-1 levels
      changed little with rhGH but fell following transplantation. A low molecular
      weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not
      clearly seen on the ligand blot. IGFBP-2 was present as a distinct band on
      Western ligand blot before transplantation and appeared decreased in intensity
      subsequently. IGFBP-1, seen on immunoblot clearly before transplant, disappeared
      after the transplant. rhGH successfully improved growth in these children, in
      association with a fourfold increase in IGF-I levels, which was maintained
      following transplantation. The reduction in IGFBPs following transplantation
      suggests correction of impaired clearance by the diseased kidney.

PMID- 8865249
TI  - Oxalate elimination via hemodialysis or peritoneal dialysis in children with
      chronic renal failure.
AB  - Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal
      dialysis (CAPD) has not been studied in detail in pediatric patients. We studied
      plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and
      children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10
      children on HD (4 female, 6 male, aged 7-18 years). Two children in each group
      had primary hyperoxaluria (PH). The mean duration of dialysis prior to
      examination was 12 +/- 11 months in CAPD and 31 +/- 23 months in HD patients.
      Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily
      exchanges in 5 patients and four changes in the remaining 10 children (dwell
      volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was
      significantly higher in HD (mean 115.6 ml/ min per 1.73 m2 in HD versus 7.14
      ml/min in CAPD), mean oxalate elimination per week was not different between both
      renal replacement therapies (3,478 mumol/1.73 m2 surface area/week in CAPD versus
      3,915 mumol/1.73 m2 per week in HD). Oxalate elimination in patients with PH was
      between 6,650 and 9,900 mumol/week. Plasma oxalate remained elevated in both
      procedures [28-84 mumol/l in CAPD (92/148 in PH) and 33-101 mumol/l in HD (70/93
      in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis
      regimen.

PMID- 8865250
TI  - Safety and cost effectiveness of pediatric percutaneous renal biopsy.
AB  - Because of the rising cost of health care, more patients are undergoing
      procedures as outpatients rather than inpatients. The purpose of this study was
      to compare safety and cost of outpatient versus inpatient, overnight stay, for
      children undergoing percutaneous renal biopsy. Charts of all such patients
      between January 1989 through January 1995 were reviewed for the following: age of
      patient, native versus allograft biopsy and preparation costs (in 1995 U.S.
      dollars), and complications. Of the 75 biopsies reviewed, 58 were native and 17
      allograft with 35 (47%) of the biopsies being outpatient and 40 (53%) inpatient.
      There were four complications (11.4%) in 2 patients for the outpatient group and
      seven complications (17.5%) in 6 patients in the inpatient group (X2 = 0.1003, P
      = 0.75). The median cost for an outpatient biopsy was U.S. $1,968 while an
      inpatient biopsy was U.S. $3,178. We conclude that outpatient percutaneous renal
      biopsy in children is as safe as inpatient and more economic, with a saving of
      greater than U.S. $1,000 per biopsy.

PMID- 8865251
TI  - An extreme example of the neonatal form of Bartter's syndrome.
AB  - A male infant is described who had polyuria over the 4 months of his life with
      urine volumes exceeding 1,000 ml/kg per day, severe serum electrolyte losses,
      metabolic alkalosis and increased plasma renin activity (56 ng/ml per hour). He
      had a normal blood pressure and glomerular filtration rate when fluid replete.
      The urine flow rate was about 25% of the glomerular filtration rate. Renal
      histology showed hyperplasia of the juxtaglomerular apparatus and abnormalities
      of the proximal tubules. The features of this case suggest an extreme form of
      Bartter's syndrome presenting from the first days of life.

PMID- 8865252
TI  - Prevalence of renal malformation in Turner syndrome.
AB  - The presence of renal malformation was evaluated in 43 patients with Turner
      syndrome (TS) and compared with the karyotype in each case; 28 patients (65%) had
      a mosaic karyotype and the other 15 (35%) had only 45,X metaphases. Renal
      malformations characteristic of TS were found in 24% of the complete sample
      group. Of the 15 cases of pure 45,X karyotype, 8 (53%) had abnormal renal
      findings, while these were found in only 2 of the 28 mosaic cases (7.1%). The
      probability of this distribution having occurred by chance is P < 0.05. More than
      50% of girls with TS are said to have a renal anomaly. In this study renal
      malformations were found in 25% of the sample group. A significantly greater
      association of renal malformation was found with monosomy 45,X than with
      mosaicism. As mosaicism occurs in up to 60% of all girls with TS, the lower
      figure reported here represents a truer prevalence than that quoted in older
      series, where the figures quoted applied only to the 45,X syndrome.

PMID- 8865253
TI  - Effect of hydrochlorothiazide in pseudohypoaldosteronism with hypercalciuria and
      severe hyperkalemia.
AB  - Severe hyperkalemia resistant to treatment with sodium chloride (NaCl)
      supplements plus cation exchange resins can be found in pseudohypoaldosteronism
      type I. In a patient with the multiple target organ variant of this condition,
      hyperkalemia persisted at dangerous levels (8.5 mmol/l) despite large doses of
      NaCl (50 mmol/kg per day) and cation exchange resins (6 g/kg per day).
      Hypercalciuria was also present. The total volume of fluids and supplements
      required was not tolerated orally. Indomethacin (2 mg/kg per day) and later
      hydrochlorothiazide (2 mg/kg per day) were tried to further correct imbalance.
      Plasma potassium (K) and Na levels, the urinary Na/K ratio, transtubular
      potassium gradient (TTKG), and urinary calcium/creatinine (Ca/Cr) ratio were used
      to evaluate the effect of hydrochlorothiazide. Under treatment, plasma Na was
      stable (137-144 mmol/l), K levels decreased from 8.5 to 5 mmol/l, urinary Na/K
      from 90 to 24, and TTKG increased from 0.3 to 1.8. Ca/Cr decreased from 3.5 to
      1.5 mmol/mmol. The dosage of cation exchange resins was decreased, oral fluids
      were tolerated, and the patient's general condition improved. Hence:
      hydroclorothiazide can be useful in the treatment of severe hyperkalemia and
      hypercalciuria of pseudohypoaldosteronism type I.

PMID- 8865254
TI  - Long-term neurological sequelae of hemolytic-uremic syndrome: a preliminary
      report.
AB  - Seven patients with hemolytic-uremic syndrome who had major neurological symptoms
      during the acute illness were neurologically and cognitively evaluated
      prospectively several years after recovery from the illness. Four patients showed
      evidence of subtle neurological sequelae, including posturing, clumsiness, poor
      fine-motor coordination, hyperactivity, and distractibility. Psychoeducational
      evaluation of all seven subjects revealed mean scores within the average range in
      cognitive abilities, academic achievement, single word receptive vocabulary,
      visual/motor planning, overall adaptive functioning, and hyperactivity. The lapse
      of time (minimum of 7 years) between the acute illness and the psychometric
      evaluation could have been responsible for our normal results.

PMID- 8865255
TI  - Nephrotic syndrome associated with an Epstein-Barr virus infection.
AB  - A 19-month-old child developed the nephrotic syndrome coincident with an Epstein
      Barr virus (EBV) infection. This rare association was confirmed by EBV titers.
      There was a spontaneous resolution of the nephrotic syndrome temporally related
      to the abatement of the EBV infection.

PMID- 8865256
TI  - Infantile nephrotic syndrome and atopy.
AB  - Nephrotic syndrome presenting in the 1st year of life is often associated with a
      very poor prognosis for normal renal function. A small proportion of patients,
      particularly boys, presenting after the first 3 months of life with idiopathic
      type, steroid-sensitive nephrosis, have a much better prognosis and may achieve
      sustained remission. We describe three boys with infantile idiopathic nephrotic
      syndrome of the mesangial proliferative glomerulonephritis type who went into
      complete remission. The patients, their first-degree relatives or both suffered
      from atopy (eczema, asthma or hayfever). This is the first report linking
      infantile nephrotic syndrome and atopy. The literature linking idiopathic
      nephrotic syndrome and atopy is reviewed, and the implications of our findings
      discussed.

PMID- 8865257
TI  - Autoimmune interstitial nephritis and hepatitis in polyglandular autoimmune
      syndrome.
AB  - A 6-year-old female with polyglandular autoimmune syndrome type I, chronic active
      hepatitis, and renal failure is described. The renal biopsy demonstrated advanced
      tubulointerstitial disease with antibodies directed against tubular basement
      membranes. The patient's serum contained circulating antibodies directed against
      both renal and hepatic parenchyma. Renal disease culminating in renal failure and
      anti-tubular basement membrane disease have not been previously reported in
      association with polyglandular autoimmune disease. We describe for the first time
      a patient with polyglandular autoimmune syndrome, chronic active hepatitis,
      circulating antibodies directed against both renal and hepatic parenchyma, and
      primary tubulointerstitial disease culminating in renal failure.

PMID- 8865258
TI  - Hepatocyte growth factor in nephronophthisis-medullary cystic disease complex.
AB  - A 13-year-old Japanese girl presented with severe anemia and renal dysfunction.
      The nephronophthisis-medullary cystic disease complex was diagnosed from the
      results of renal biopsy and a family study. Immunohistochemical detection of
      hepatocyte growth factor in the epithelial cells of dilated renal tubules
      suggested that it may have a role in the development of the tubular cystic
      changes which are characteristic of this disease.

PMID- 8865259
TI  - Factors predisposing to urinary tract infections in children.
AB  - The normal urinary tract is sterile for many reasons. These include: bacterial
      eradication by urinary and mucus flow, urothelial bactericidal activity, urinary
      secretory IgA, and blood group antigens in secretions which interfere with
      bacterial adherence. Periodic emptying of the bladder should wash bacteria out,
      but uropathogens grow well in urine and their rapid doubling time might not clear
      bacteria by voiding at the usual frequency. The ability to colonize the gut, as
      well as adhere to host squamous and urothelial cells, is due to bacterial
      adherence, a mechanism by which fluid washout would not be effective. Fimbriae or
      pili, hair-like surface appendages of Escherichia coli, are the usual adhesins.
      E. coli with type 1 fimbriae adhere to mucus, and P-fimbriae adhere to
      glycolipids on mucous membranes and urothelial cells. Other common virulence
      factors of E. coli include the capsule, which prevents phagocytosis, hemolysin,
      which damages urothelium, and aerobactin, which sequesters iron. Adherence
      stimulates the inflammatory response by activation of cytokines such as
      interleukin-1, -6, and -8. These cytokines stimulate the production of
      intercellular adhesion molecule, which by leukocyte adhesion causes migration of
      these cells to the site of infection to counteract it.

PMID- 8865260
TI  - Integrin receptors, the cytoskeleton, and glomerular cell function.

PMID- 8865261
TI  - Nitric oxide in the developing kidney.
AB  - Although nitric oxide (NO) has a well-established role in regulating renal
      function in the adult, recent studies point to perhaps an even more critical role
      for NO in maintaining basal renal blood flow (RBF) and glomerular filtration rate
      (GFR) in the developing kidney. The immature kidney has enhanced renal
      hemodynamic and functional responses to stimulation and inhibition of NO
      synthesis when compared with the adult, and these increased responses are not
      mediated by prostaglandins. Increased intrarenal activity of NO in the developing
      kidney counter-regulates the highly activated renin angiotensin system by
      modulating the angiotensin II-mediated vasoconstriction of the developing renal
      vasculature, the angiotensin II effects on GFR, as well as renin release.
      Localization studies demonstrate that NO acts on neonatal RBF and stabilization
      of GFR through an intrarenal distribution of the synthesizing enzyme, nitric
      oxide synthase, that is different from that of the adult. The developing kidney
      is dependent on NO to maintain RBF and GFR during periods of hypoxemia,
      protecting against renal injury, such as acute renal failure. In summary, NO is
      vital in the developing kidney to maintain normal physiological function and to
      protect the immature kidney during pathophysiological stress.

PMID- 8865262
TI  - Clinical quiz. Osteoid osteoma.

PMID- 8865263
TI  - Hypercalcaemia, hypercalciuria and nephrocalcinosis in Down syndrome.

PMID- 8865264
TI  - Spontaneous resolution of upper urinary tract obstruction in an anuric premature
      neonate.

PMID- 8865265
TI  - Modulators of the renin-angiotensin-aldosterone system and cough in childhood.

PMID- 8865266
TI  - One patient's experience with mycophenolic acid.

PMID- 8865267
TI  - Use of a modified peritoneal equilibration test to optimize solute and water
      clearance.

PMID- 8865268
TI  - Glomerulonephritis in children with Down syndrome.

PMID- 8865269
TI  - Protracted levamisole in children with frequent-relapse nephrotic syndrome.

PMID- 8865270
TI  - Development of immune functions related to allergic mechanisms in young children.
AB  - The newborn immune system differs quantitatively and functionally from that of
      adults. Development of the immune system has important implications for childhood
      diseases. The immaturity of the immune system in the first years of life may
      contribute to failure of tolerance induction and in the development of allergic
      disease. T cell function is diminished, especially the capacity to produce
      cytokines; production of interferon (IFN)-gamma, and IL-4 is strongly reduced.
      IFN-gamma has been found to be even lower in cord blood of newborns with a family
      history of atopy. Differences in other cell types (natural killer cells, antigen
      presenting cells, and B cells) could also play a role in the development of
      allergic disease. Current data suggest that irregularities in IgE synthesis,
      helper T cell subsets (Th1, Th2, CD45RA, and CD45RO), cytokines (IL-4, IFN
      gamma), and possibly other cell types may play a role in the development of
      allergy in childhood. Moreover, the role of cell surface molecules, like co
      stimulatory molecules (CD28, CD40L), activation markers (CD25), and adhesion
      molecules (LFA-1/ICAM-1, VLA-4/ VCAM-1) is also discussed. These variables are
      modulated by genetic (relevant loci are identified on chromosome 5q, 11q, and 14)
      and environmental forces (allergen exposure, viral infections, and smoke). The
      low sensitivity of current predictive factors for the development of allergic
      diseases, such as cord blood IgE levels, improves in combination with family
      history and by measurement of in vitro responses of lymphocytes and skin
      reactivity to allergens. New therapeutic approaches are being considered on the
      basis of our current understanding of the immunopathology of allergic disease,
      for instance cytokine therapy and vaccination with tolerizing doses of allergen
      or peptides.

PMID- 8865271
TI  - Erythropoietin receptors are expressed in the central nervous system of mid
      trimester human fetuses.
AB  - Recombinant erythropoietin (rEpo) is an effective treatment for infants with the
      anemia of prematurity. rEpo was previously thought to act only on erythroid
      progenitor cells, but evidence now indicates that certain nonerythroid cells also
      express functional erythropoietin receptors (Epo-R). Such receptors have been
      observed on cells in the developing murine brain and spinal cord. The objective
      of this study was to determine whether Epo-R are expressed in the CNS of mid
      trimester human fetuses. For this study, spinal cords were collected from five
      mid-trimester abortuses. RNA was extracted from the washed specimens, and the
      presence of Epo-R mRNA was sought by reverse transcription followed by polymerase
      chain reaction. Immunohistochemistry was then used to determine the anatomic
      location of the cells expressing Epo-R within the fetal spinal cord. The results
      showed that all fetal spinal cords tested contained Epo-R mRNA. The cells
      expressing Epo-R were radiating from the ependymal canal toward the anterior and
      posterior median sulci. We conclude that Epo-R are expressed on cells in the
      developing human CNS. Further studies are needed to determine whether they are
      clinically relevant in the premature infant.

PMID- 8865272
TI  - Recombinant human erythropoietin: possible role as an antioxidant in premature
      rabbits.
AB  - Iron is an important catalyst for free oxygen radicals and lipid peroxidation
      reactions which may play a role in the pathogenesis of several diseases in
      premature infants. During the early neonatal period, extracellular iron is
      available in excessive amounts. We hypothesized that administration of
      erythropoietin (EPO) mobilizes iron from plasma and inhibits iron-catalyzed
      reactions. To evaluate this hypothesis, recombinant human EPO (rhEPO) was
      administered s.c. to premature rabbits delivered at 29-d gestation: one group was
      kept in room air (RA) and the other in a 100% oxygen environment. Within each
      group, the animals were randomized to receive placebo or rhEPO at 400 or at 800
      U/kg on d 0 and 2 of life. On d 3 or 4, plasma iron and iron saturation of
      transferrin were assessed. Lipid peroxidation was analyzed in plasma and
      bronchoalveolar lavage fluid (BAL). Nonsedimentable protein (NSP) and
      phospholipid content were measured in BAL. Erythropoiesis was evaluated in liver
      and bone marrow. Treatment with rhEPO decreased plasma iron, decreased iron
      saturation of transferrin, increased reticulocytes, and increased erythropoiesis
      in liver and bone marrow in both RA and hyperoxia group. Oxygen exposure
      increased NSP in BAL and decreased the ability of BAL to inhibit lipid
      peroxidation as measured by malondialdehyde (MDA) generation compared with RA
      exposure. In O2-exposed animals, EPO treatment increased the ability of both
      plasma (EPO 800) and BAL (EPO 400 and 800) to inhibit lipid peroxidation and
      decreased NSP in BAL (EPO 400). In addition, rhEPO treatment decreased alveolar
      thickening and proteinaceous exudate in the hyperoxia group. We propose that by
      stimulating erythropoiesis, rhEPO mobilizes non-heme iron and decreases oxidant
      injury that depends on the availability of transient metal.

PMID- 8865273
TI  - Synergistic response of cord blood myeloid progenitor cells to the combined
      administration of human granulocyte colony-stimulating factor and human stem cell
      factor in vitro.
AB  - We compared the in vitro response of myeloid progenitor cells [colony-forming
      units of culture (CFU-C)] that were prepared from human umbilical cord blood to
      the administration of the combination of granulocyte colony-stimulating factor (G
      CSF) and stem cell factor (SCF) versus that of CFU-C obtained from normal human
      bone marrow. Progenitors were purified according to CD34 expression; the number
      and size of colonies were evaluated by culture in agar or methylcellulose,
      respectively. In the presence of G-CSF alone, the mean number of colonies was
      significantly greater in the bone marrow culture versus that of cord blood. SCF
      alone bad little effect on colony formation, but in the presence of optimal or
      suboptimal concentrations of G-CSF, SCF significantly increased colony formation
      from both cell sources. Its effect on cord blood significantly exceeded that on
      bone marrow. SCF used in combination with G-CSF significantly increased the size
      of the colonies with cord blood CFU-C; this effect was less marked with bone
      marrow CFU-C. The percentage of cells that expressed c-Kit, the SCF receptor, did
      not appear to differ between the two sources of CFU-C. Results indicate that cord
      blood CFU-C showed a greater response to SCF in combination with G-CSF than did
      bone marrow CFU-C.

PMID- 8865274
TI  - Maternal acute fatty liver of pregnancy associated with fetal trifunctional
      protein deficiency: molecular characterization of a novel maternal mutant allele.
AB  - Acute fatty liver of pregnancy (AFLP) is a devastating late gestational
      complication with many similarities to the inherited disorders of mitochondrial
      fatty acid oxidation. We report the molecular defects in a woman with AFLP and
      her infant who subsequently was diagnosed with trifunctional protein (TFP)
      deficiency. We used single-stranded conformation variance and DNA sequence
      analyses of the human TFP alpha-subunit gene, which encodes the long chain 3
      hydroxyacyl-CoA dehydrogenase (LCHAD) activity, to demonstrate a C to T mutation
      (C1678T) in exon 16 present on one allele in the mother and the affected infant.
      This creates a premature termination codon (R524Stop) in the LCHAD domain. Using
      reverse transcriptase-PCR amplification of the alpha-subunit mRNA from cultured
      fibroblasts, we demonstrated that transcripts containing this R524Stop mutation
      are present at very low levels, presumably because of rapid mRNA degradation. The
      affected infant also had the common E474Q mutation (nucleotide G1528C) on the
      second allele. Thus, he is a compound heterozygote. The father and two normal
      siblings are heterozygous for this E474Q mutation. This initial delineation of
      the R524Stop mutation provides evidence of the heterogeneity of genetic defects
      responsible for TFP deficiency and AFLP.

PMID- 8865275
TI  - Effects of the 21-amino steroid tirilazad mesylate (U-74006F) on brain damage and
      edema after perinatal hypoxia-ischemia in the rat.
AB  - Using 7-d-old rat pups, the neuroprotective efficacy of the lipid peroxidation
      inhibitor tirilazad mesylate (U-74006F) was tested in a model of perinatal
      hypoxic-ischemic (HI) brain damage. The experimental protocol was divided into
      five parts: 1) pre- plus post-HI treatment or 2) only post-HI treatment with
      tirilazad (7.5 mg/kg intraperitoneally) or vehicle with evaluation of hemispheric
      weight deficit 14 d after the insult; 3) post-HI treatment with tirilazad or
      vehicle with histopathologic evaluation 14 d after the insult; 4) pre- plus post
      HI treatment; or 5) posthypoxic treatment with tirilazad or vehicle with
      evaluation of brain edema 20 h after the insult. In the pre- plus post-HI
      treatment group, the mean left hemispheric weight deficit was 20.7% +/- 17.8
      (mean +/- SD) in tirilazad-treated rats and 27.5% +/- 20.4 in vehicle-treated
      rats (p = 0.032). Corresponding values for the post-HI treated animals were 19.6%
      +/- 16.0 and 28.6% +/- 15.4 (p = 0.043). Histopathologic injury assessed as
      pathology score on a scale of 0-5 was less extensive in tirilazad-treated animals
      compared with controls (p = 0.038). There was a significant increase in water
      content in the HI hemisphere compared with the contralateral (hypoxic)
      hemispheres in tirilazad- and vehicle-treated animals. This increase of water
      content in the HI hemispheres did not differ between tirilazad- and vehicle
      treated animals. The lipid peroxidation inhibitor tirilazad administered after
      perinatal HI reduced brain damage by 30%, but no effect was found on early
      postinsult edema.

PMID- 8865276
TI  - Magnetic resonance imaging and spectroscopy of the brain in propionic acidemia:
      clinical and biochemical considerations.
AB  - Three patients with propionic acidemia were studied. The first patient was
      diagnosed at the age of 9 mo, 3 mo after he developed hypotonia and
      choreoathetoid movements after an upper respiratory tract infection. The second
      patient was diagnosed at the age of 1.5 mo when she became comatose after
      nasogastric tube feeding because of failure to thrive. The third patient was
      diagnosed at the age of 5 d when she presented with feeding difficulties,
      hypotonia, and respiratory insufficiency. Magnetic resonance imaging (MRI) of the
      brain in all patients revealed delayed myelination and some cerebral atrophy. In
      the patient with choreoathetosis, MRI showed bilateral abnormalities in the
      signal intensity of the putamen and caudate nuclei. MRI of the other two patients
      showed normal basal ganglia. Proton magnetic resonance spectroscopy (1H MRS) from
      a voxel located in the basal ganglia revealed a decrease in N-acetylaspartate and
      myo-inositol peaks and an elevation of glutamine/ glutamate. The presence of
      spectroscopic abnormalities in a stable metabolic condition, in particular the
      rise in glutamine/ glutamate, indicates that the metabolic balance on cerebral
      parenchymal level is less optimal than estimated from biochemical analysis of
      urine, plasma, or cerebrospinal fluid.

PMID- 8865277
TI  - Fuel utilization by early newborn brain is preserved under congenital
      hypothyroidism in the rat.
AB  - Mental retardation associated with hypothyroidism may be caused by impairment of
      brain ketone body-metabolizing enzymes during the suckling period. However, much
      evidence suggests that, immediately after delivery, lactate, instead of ketone
      bodies or glucose, may be the best substrate for the brain. In this work, we have
      studied the effect of experimentally induced congenital hypothyroidism on the
      rate of lactate, glucose, and 3-hydroxybutyrate utilization in early neonatal
      brain slices. Methimazole (MMI) administration to the mothers caused a 5.4- and
      1.7-fold decrease in neonatal plasma concentrations of L-thyroxine (T4) and
      3,5,3'-triiodo-L-thyronine (T3), respectively. Propylthiouracil (PTU)
      administration to the mothers caused a 7.3- and > 2-fold decrease in plasma T4
      and T3 concentrations, respectively. MMI-induced hypothyroidism did not
      significantly modify the rate of lactate, glucose, or 3-hydroxybutyrate oxidation
      to CO2 and their incorporation into lipids by the neonatal brain. However, PTU
      induced hypothyroidism decreased the rate of lactate and glucose oxidation to CO2
      and their incorporation into lipids by 17% (p < 0.05). 3-Hydroxybutyrate
      utilization was not modified by this treatment. Separation by HPLC of the lipids
      revealed that PTU-mediated inhibition of lipid synthesis from lactate and glucose
      may be accounted for by specific inhibition of the rate of sterol synthesis (15%,
      p < 0.05), whereas the rate of phospholipid synthesis was unaffected. These
      results suggest that the early newborn may develop mechanisms aimed at avoiding
      the possible brain damage caused by the inhibition of lipid synthesis brought
      about by mild neonatal hypothyroidism.

PMID- 8865278
TI  - Escherichia coli transcytosis in a Caco-2 cell model: implications in neonatal
      necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a serious gastrointestinal disorder of preterm
      infants. Other than an association with prematurity and gastrointestinal feeding,
      no single factor or mechanism has been consistently linked to this disease. We
      have previously demonstrated that Escherichia coli isolates obtained from the
      stool of infants with NEC caused NEC-like injury in a weanling rabbit ileal loop
      model; this injury, in turn, could be blocked by coinfection with selected
      Gram(+) bacteria (Enterococcus faecium) isolated from asymptomatic controls.
      Using Caco-2 cells in a trans-well system, we now demonstrate that the same E.
      coli isolates can cross epithelial cell monolayers in the absence of
      ultrastructural change or damage. These results with E. coli contrast with those
      seen with Salmonella typhimurium, which passed through the monolayer at a higher
      rate and were associated with striking ultrastructural damage. Transcytosis of E.
      coli was reduced 3-5-fold in the presence of E. faecium previously shown to block
      NEC-like injury in the loop model. There was a mild increase in the rate of E.
      coli transcytosis when studies were conducted with younger, undifferentiated
      cells; these immature cells had no brush border, had decreased production of
      brush border-specific enzymes, but retained well defined tight junctions, as
      demonstrated by transepithelial electrical resistance and electron microscopy. A
      further reduction/ complete blockage of E. coli transcytosis was observed when E.
      faecium was used as the coinfectant in studies with these undifferentiated cells.
      We hypothesize that the ability of E. coli to cross epithelial cell layer is a
      critical initial step in the cascade of events which lead ultimately to NEC;
      blockage or reduction in E. coli transcytosis in the presence of certain Gram(+)
      organisms may play a significant role in prevention of NEC.

PMID- 8865279
TI  - Allopurinol reduces bacterial translocation, intestinal mucosal lipid
      peroxidation, and neutrophil-derived myeloperoxidase activity in chronic portal
      hypertensive and common bile duct-ligated growing rats.
AB  - Bacterial translocation (BT) from the gastrointestinal tract has been thought to
      play a role in the pathogenesis of septic complications in patients with chronic
      portal hypertension (PH) and obstructive jaundice. The purpose of this study was
      to investigate the incidence of BT and to assess the role of intestinal mucosal
      malondialdehyde (MDA) levels as an indicator of lipid peroxidation and
      polymorphonuclear neutrophil-derived myeloperoxidase (MPO) in chronic portal
      hypertensive and common bile duct-ligated rats. Twenty male rats were subjected
      to sham laparotomy (SL), 20 rats to calibrated portal vein constriction (PH), 20
      rats to common bile duct ligation (CBDL), and 10 rats served as a nonoperated
      control group (NOP). After 4 wk, 10 animals of each operated group received 50
      mg/kg allopurinol intraperitoneally, at 24 h, and again 2 h prior to estimation
      of BT, intestinal mucosal MDA, and MPO activities. In the NOP and SL groups, BT
      to the mesenteric lymph nodes (MLN) and spleen was present. In PH and in CBDL
      rats, BT to liver, portal vein, peritoneum, and caval vein occurred. Allopurinol
      treatment attenuated the frequence of BT in PH and decreased BT in CBDL rats
      significantly (p < 0.05). Ileal mucosal MDA levels (nanomoles/g) in untreated
      rats increased from 45.1 +/- 7.9 in SL to 98.2 +/- 9.1 in PH and to 102.2 +/- 11
      in CBDL rats (p < 0.01). In the allopurinol groups the increase of MDA to 49.1 +/
      1.3 in PH, and 66.2 +/- 2.2 in CBDL was significantly lower (p < 0.01). MPO
      activity (units/g) in the ileal mucosa increased in untreated rats from 319 +/-
      129 after SL to 866 +/- 104 after PH and to 1016 +/- 104 after CBDL (p < 0.01).
      Allopurinol significantly attenuated MPO activity to 369 +/- 44 in PH, and to 372
      +/- 60 in CBDL animals (p < 0.01). In PH and CBDL rats significant BT, intestinal
      mucosal lipid peroxidation, and polymorphonuclear neutrophil-derived MPO activity
      occurred. Allopurinol reduced BT and improved intestinal mucosal MDA and MPO
      activities, suggesting that there might be an association between BT and
      intestinal mucosal lipid peroxidation.

PMID- 8865280
TI  - Effect of human milk or formula on gastric function and fat digestion in the
      premature infant.
AB  - The effect of diet, human milk or formula, on gastric function (lipase and pepsin
      activity, pH, and volume) and intragastric digestion of fat was assessed in 28
      appropriate for gestational age preterm infants (gestational age, 28.9 +/- 1.4,
      29.1 +/- 0.9, 29.5 +/- 0.6 wk; birth weight, 1.00 +/- 0.14 to 1.18 +/- 0.07 kg).
      The infants were fed either human milk (n = 11), SMA Super Preemie formula (n =
      9), or Similac, Special Care formula (n = 8). Fasting and postprandial activity
      of digestive enzymes, pH, and gastric volume (measured before or during 50 min
      after gavage feeding) did not differ as a function of diet among the three groups
      of infants. Gastric lipase output, 23.1 +/- 5.1, 28.3 +/- 6.6, and 22.5 +/- 6.4
      (U/kg of body weight) in human milk-, SMA SP-, or Similac SC-fed infants was
      comparable to the gastric lipase output of healthy adults fed a high fat diet
      (22.6 +/- 3.0). Pepsin output was, however, significantly lower (597 +/- 77, 743
      +/- 97, and 639 +/- 142 U/kg of body weight) in human milk-, SMA SP-, and Similac
      SC-fed infants) than in healthy adults (3352 +/- 753 U/kg). The hydrolysis of
      dietary fat was 1.7-2.5-fold higher (p < 0.01) in human milk-fed infants than in
      infants fed either formula. We conclude that differences in type of feeding, i.e.
      different fatty acid profiles (long chain or medium chain triglycerides),
      different emulsions (natural or artificial), and different fat particle sizes do
      not affect the level of activity of gastric enzymes. However, the triglyceride
      within milk fat globules appears to be more accessible to gastric lipase than
      that within formula fat particles. We suggest that the contribution of gastric
      lipase to overall fat digestion might be greater in the newborn (a period of
      pancreatic insufficiency) than in the adult.

PMID- 8865281
TI  - Chronic maternal undernutrition in the rat leads to delayed postnatal growth and
      elevated blood pressure of offspring.
AB  - To determine the effects of chronic maternal undernutrition on postnatal somatic
      growth and blood pressure, pregnant dams were randomly assigned to one of two
      dietary treatment groups. A control group was fed ad libitum throughout pregnancy
      and a restricted group was fed 30% of ad libitum intake. From birth, feeding was
      ad libitum in both groups, and litter size was adjusted to eight pups per litter.
      Litter size was not significantly altered by the reduced maternal intake.
      Offspring of the restricted fed group were significantly smaller than offspring
      from the ad libitum fed group from birth until 12 wk of age, but by 30 wk had
      similar body weights. Blood pressure was measured by tail cuff plethysmography.
      Offspring from the restricted fed group were found to have significantly (p <
      0.05) elevated systolic blood pressure (5-8 mm Hg) at 30, 48, and 56 wk of age.
      These data demonstrate that nutritional deprivation in the pregnant rat leads to
      changes in postnatal allometric growth patterns, to delayed catch-up growth, and
      to elevated blood pressure in adulthood. The data are consistent with the
      hypothesis that poor maternal nutrition in pregnancy may irreversibly alter
      programming of the development of cardiovascular homeostasis.

PMID- 8865282
TI  - Wheat kernel ingestion protects from progression of muscle weakness in mdx mice,
      an animal model of Duchenne muscular dystrophy.
AB  - A simple, reproducible test was used to quantify muscle weakness in mdx mice, an
      animal model of Duchenne muscular dystrophy. The effect of bedding on wheat
      kernels and of dietary supplementation of alpha-tocopherol on the progression of
      muscle weakness was investigated in mdx mice. When measured during the first 200
      d of life, mdx mice developed muscle weakness, irrespective of bedding and diet.
      When kept on wood shavings and fed a conventional rodent diet, mdx mice showed
      progressive muscle weakness over the consecutive 200 d, and eventually showed a
      significant weight loss during the next 200-d observation period. Progression of
      muscle weakness and weight loss were almost completely prevented in mdx mice that
      were kept on wheat kernel bedding. In contrast, only incomplete maintenance of
      muscle strength and body weight was observed in mdx mice kept on wood shavings
      and fed the alpha-tocopherol-supplemented diet. It is concluded from these
      experiments that a component of wheat kernels other than alpha-tocopherol is
      essential to prevent the progression of muscle weakness in mdx mice.

PMID- 8865283
TI  - Mitogenic and antiadipogenic properties of human growth hormone in
      differentiating human adipocyte precursor cells in primary culture.
AB  - Children with GH deficiency have enlarged fat cells but a reduced number of fat
      cells compared with healthy children. After treatment with human GH (hGH) both
      fat cell volume and number are shifted toward normal. To clarify the role of hGH
      in fat cell formation in human adipose tissue, we investigated the effect of hGH
      on the proliferation and the differentiation of cultured human adipocyte
      precursor cells obtained from five children and 10 adults. In a chemically
      defined serum-free medium treatment of adipocyte precursor cells with hGH led to
      an increase in IGF-I production and a stimulation of cell proliferation, which
      could be blocked by a MAb raised against human IGF-I. hGH dose-dependently
      reduced the number of differentiating cells and suppressed the expression of
      glycerol-3-phosphate dehydrogenase (GPDH), a marker of adipose differentiation.
      No significant differences in the hGH effects on proliferation and
      differentiation capacities were seen between cultures obtained from children and
      adults. In newly differentiated adipocytes, hGH inhibited glucose uptake and
      lipogenesis, and stimulated lipolysis. Scatchard analysis of hGH competition
      experiments using 125I-labeled hGH yielded a linear plot with an apparent Kd of
      1.08 nM and an estimated number of 7000 hGH receptors per cell. These data
      suggest that hGH is able to enlarge the human adipocyte precursor pool via
      induction of IGF-I synthesis but exhibits a direct antiadipogenic activity. hGH
      is also able to reduce fat cell volume by reducing lipogenesis and increasing
      lipolysis.

PMID- 8865284
TI  - Glycolysis is not responsible for the tolerance of immature renal tubules to
      anoxia.
AB  - We have previously shown that the immature tubule is tolerant of prolonged
      anoxia. In addition, cellular ATP is maintained at 2-fold higher levels during
      anoxia in the immature tubules compared with the mature tubules. The purpose of
      this study was: 1) to determine whether anaerobic glycolysis contributes to the
      tolerance to anoxia and preservation of cellular ATP in immature tubules and 2)
      to evaluate whether the tolerance demonstrated by immature tubules is dependent
      on preservation of cellular ATP. Suspensions of proximal tubules from immature (8
      10 d) and mature (8-10 wk) rats were subjected to 15 and 45 min of anoxia in a
      standard buffer and in buffers designed to inhibit glycolysis. Lactate
      dehydrogenase release was used to assess plasma membrane damage, ATP levels were
      determined as an index of cellular energy and total lactate production was
      measured to evaluate glycolytic activity. After 45 min of anoxia, total lactate
      production was less in immature tubules (101 +/- 48 micrograms of lactate/mg of
      DNA) compared with mature tubules (148 +/- 36 micrograms of lactate/mg of DNA).
      After inhibition of glycolytic metabolism, ATP decreased to similar levels in
      both immature and mature tubules. However, immature tubules remained resistant to
      anoxic damage (lactate dehydrogenase: mature tubules 38 +/- 4%, immature tubules
      29 +/- 1.0%). Therefore, enhanced glycolytic activity does not play a dominant
      role in the tolerance of the developing kidney to anoxia, and this tolerance is
      not primarily dependent on preservation of cellular ATP.

PMID- 8865285
TI  - L-type calcium current in pediatric and adult human atrial myocytes: evidence for
      developmental changes in channel inactivation.
AB  - Animal studies have documented the presence of marked, species-dependent,
      developmental changes in the properties of the L-type calcium current in cardiac
      myocytes. In an effort to understand the postnatal changes which occur in the
      calcium current in human heart, we characterized the calcium current in atrial
      myocytes isolated from 17 pediatric and older children (ages 3 d to 14 y) and 12
      adult (ages 43-79 y) human hearts using the whole-cell patch clamp technique. In
      contrast to animal models, we found no evidence for age-related changes in
      calcium current density, steady-state inactivation, or kinetics of recovery from
      inactivation, suggesting that, in human atrium, calcium channels are in many
      aspects functionally mature at the time of birth. However, statistically
      significant differences were found in the kinetics of calcium current
      inactivation, with calcium current measured in cells isolated from pediatric
      human atria inactivating approximately 2-fold faster than cells isolated from
      adult hearts. These results suggest a possible role for age-related changes in
      calcium current inactivation in the shortened action potential duration observed
      in pediatric compared with adult human atrium.

PMID- 8865286
TI  - Effects of treatment with pentoxifylline on the cardiovascular manifestations of
      group B streptococcal sepsis in the piglet.
AB  - Pentoxifylline (PTXF) is a methylxanthine derivative which modifies leukocyte
      function and inhibits tumor necrosis factor (TNF)-alpha release. As TNF-alpha is
      considered a proximal mediator in the cascade leading to septic shock, we
      evaluated the ability of PTXF to attenuate the cardiovascular manifestations of
      sepsis secondary to an infusion of group B beta-hemolytic streptococci (GBS).
      Fifteen anesthetized, mechanically ventilated piglets (weight, 2815 +/- 552 g)
      were randomly assigned to a treatment group which received a continuous infusion
      of PTXF (5 mg/kg/h) beginning 30 min after GBS (7.5 x 10(8) colony-forming
      units/kg/min) administration was started or to a control group which received GBS
      plus saline as placebo. Comparison of the hemodynamic measurements and arterial
      blood gases over the first 120 min of bacterial infusion for treatment and
      control groups revealed the following statistically significant differences (120
      min values presented): cardiac output was significantly higher in the PTXF group
      (0.159 +/- 0.035 versus 0.09 +/- 0.026 L/kg/min; p < 0.05) as was stroke volume
      (0.54 +/- 0.11 versus 0.27 +/- 0.126 mL/kg/beat; p < 0.01). Pulmonary and
      systemic vascular resistances remained lower in the PTXF-treated animals (167 +/-
      45 versus 233 +/- 69 mm Hg/L/kg/min; p < 0.03) and (427 +/- 162 versus 828 +/-
      426 mm Hg/L/kg/min; p < 0.03, respectively). Median survival time was
      significantly longer in the PTXF group (180 versus 120 min; p < 0.05). In an
      additional group of animals, PTXF administration before GBS infusion revealed no
      attenuation in the rise of TNF-alpha, accompanying sepsis. These data demonstrate
      that treatment with PTXF may ameliorate some of the deleterious hemodynamic
      manifestations of GBS sepsis and result in improved survival in a young animal
      model without significantly modifying plasma TNF-alpha levels.

PMID- 8865287
TI  - Decreased interleukin-10 production by neonatal monocytes and T cells:
      relationship to decreased production and expression of tumor necrosis factor
      alpha and its receptors.
AB  - The production of IL-10 by human neonatal blood mononuclear leukocytes (BML)
      stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF
      alpha), antibodies to CD3, or phorbol 12-myristate 13-acetate (PMA) was measured.
      The production of IL-10 by neonatal BML cultured with LPS or TNF-alpha was
      approximately 20 and approximately 15%, respectively, of adult BML. The
      combination of human recombinant TNF-alpha and LPS failed to augment IL-10
      production in neonatal BML. The decreased production of IL-10 by neonatal
      leukocytes was not due to an autocrine feedback mechanism because only low
      concentrations of IL-10 were found in newborn sera. A connection with TNF-alpha
      could not be ruled out, because TNF-alpha production by LPS-stimulated newborn
      BML and the expression of TNF-alpha receptors on newborn monocytes were reduced.
      Mean +/- SD of concentrations of IL-10 in supernatants from adult and neonatal
      BML after stimulation with antibodies to human CD3 for 48 or 72 h were 914 +/-
      386 and 178 +/- 176 pg/mL, respectively (p < 0.0001). In experiments with
      enriched populations of neonatal T cells, the addition of PMA failed to augment
      IL-10 production. This suggested that newborn T cells may be in a different state
      of activation than adult T cells Thus, IL-10 production in neonatal monocytes and
      T cells is reduced and this study suggests that the reduction may be secondary in
      part to regulatory processes involving TNF-alpha and its receptors.

PMID- 8865288
TI  - Mucosal tumor necrosis factor-alpha production and extensive disruption of
      sulfated glycosaminoglycans begin within hours of birth in neonatal respiratory
      distress syndrome.
AB  - Many of the clinicopathologic features of neonatal respiratory distress syndrome
      (RDS) may be related to the inflammatory response mounted by the affected infant,
      although little is known about the interstitial component of this response. We
      have thus studied the local inflammatory response in this condition by
      immunohistochemical analysis of whole lung lobes, obtained at postmortem from 40
      infants who died from acute RDS in the first week of life. All had demonstrated
      classical clinical history and histologic features. An archival subgroup from the
      early 1970s had never received ventilatory support. Immunohistochemical analysis
      demonstrated rapid temporal increase from birth in the mucosal density of CD68+
      macrophages, MAC-387+ monocytes/macrophages, polymorphonuclear neutrophils, and
      tumor necrosis factor-alpha-immunoreactive cells, maximal in those dying at or
      after 72 h. Using a cationic probe specific for sulfated glycosaminoglycans
      (GAGs), the inflammatory infiltration was seen to be associated with striking
      loss of endothelial, basement membrane, and interstitial GAGs, which was almost
      complete by 48-72 h. GAG degradation products were found within hyaline membranes
      in all infants dying after 48 h. This study confirms that neonatal RDS is
      characterized by intense interstitial inflammation, significantly underestimated
      on routine staining. This begins within hours of birth and is maximal by 72 h of
      age. Breakdown of sulfated GAGs within the extracellular matrix follows the same
      time course and may explain much of the physiologic derangement characteristic of
      this condition.

PMID- 8865289
TI  - Early production of macrophage inflammatory protein-1 alpha occurs in respiratory
      distress syndrome and is associated with poor outcome.
AB  - Although progression to pulmonary fibrosis in preterm infants with respiratory
      distress syndrome (RDS) is related to the inflammatory response, the nature of
      this response remains controversial. We have therefore performed sequential
      bronchoalveolar lavages in 30 infants with RDS (13 of whom developed
      bronchopulmonary dysplasia) and 7 ventilated control infants, characterizing the
      cells obtained by immunohistochemical analysis of lineage-specific markers and
      assaying macrophage-associated chemokines and cytokines in supernatant fluid. At
      all ages from birth, lavage supernatants demonstrated highly significant increase
      over controls of the beta-chemokine macrophage inflammatory protein (MIP)-1
      alpha, although not of regulated upon activation, normal T cell expressed and
      secreted (RANTES), of the cytokines tumor necrosis factor (TNF)-alpha and IL-1
      beta, and of elastase/alpha-1 antitrypsin. Significantly higher concentrations of
      MIP-1 alpha in particular were associated with the later development of fibrosis.
      Increased numbers of macrophages expressing the activation marker RM/3-1 were
      found at all ages in bronchopulmonary dysplasic infants, whereas neutrophil
      numbers were increased from d 3. Dexamethasone administered to 10 infants induced
      rapid decrease in inflammatory cell numbers and concentrations of MIP-1 alpha,
      tumor necrosis factor-alpha, IL-1 beta, and elastase/alpha-1 antitrypsin. The
      inflammatory response in neonatal RDS begins within the first day of life. Long
      term outcome is associated with the magnitude of this early response, in
      particular production of MIP-1 alpha. The early introduction of specific therapy
      is thus likely to be beneficial.

PMID- 8865290
TI  - Characterization of natural killer and antibody-dependent cellular cytotoxicity
      of preterm infants against human immunodeficiency virus-infected cells.
AB  - The odds risk of vertical transmission of human immunodeficiency virus (HIV) to
      preterm infants is almost four times that of term infants and may relate to
      maternal and neonatal factors. We characterized the competence of early
      nonspecific cellular immunity, namely natural killer cytotoxicity (NKC) and
      antibody-dependent cellular cytotoxicity (ADCC), of peripheral blood mononuclear
      cells (PBMC) from preterm (n = 20) and term neonates (n = 28) versus adult
      controls against a T cell line infected with the human T cell lymphotrophic virus
      III(B) using a chromium-51 release assay. PBMC from term neonates exhibited
      levels of NKC activity equal to adults against HIV-infected targets, yet the NKC
      capacity of preterm neonatal PBMC was significantly diminished. The ADCC activity
      of both term and preterm neonatal PBMC against HIV-infected targets was
      significantly less than that of adult PBMC. Overnight stimulation of a subset of
      samples with IL-12 augmented the NKC activity of both infant groups and adults,
      whereas the ADCC activity remained unchanged. These findings demonstrate that
      term neonates are deficient in ADCC against HIV-infected targets, whereas preterm
      infants are deficient in both NKC and ADCC, which may relate, in part, to the
      increased risk of transmission of HIV with preterm delivery. In addition, IL-12
      has the potential to augment both term and preterm neonatal antiviral defense.

PMID- 8865291
TI  - The effect of temperature on the ventilatory response to carbon dioxide in the
      neonatal rat.
AB  - The rectal temperature of newborn rats in the nest varies between 32 and 39
      degrees C, depending on environmental temperature and the presence of the dam.
      Because rebreathing of CO2 occurs in the nest, experiments were carried out to
      examine the effects of body temperature on the ventilatory response (VR) to CO2
      at different postnatal ages. The VR to 2 and 4% carbon dioxide was examined in
      rat pups by the body plethysmograph method whereas rectal temperature was
      manipulated to 32-33 degrees C, 36-37 degrees C, and 38-39 degrees C. At three
      different ages, 2-3 d, 5-6 d, and 8-9 d, rat pups had a VR to both concentrations
      of CO2 due, principally, to an increase in tidal volume (Vt). Ventilation (Vi) in
      air was highest at the lowest rectal temperature, and there was a significant,
      inverse correlation with temperature in the 2-3-d-old and 5-6-d-old rats. The VRs
      to 2 and 4% CO2 were significantly, inversely, related to body temperature in the
      youngest group. The direction of temperature modification also had a significant
      effect, because VRs to both 2 and 4% CO2 were significantly lower in rat pups
      which were being warmed compared with those being cooled.

PMID- 8865292
TI  - Carbon dioxide chemosensitivity and exercise ventilation in healthy children and
      in children with cystic fibrosis.
AB  - This two-part study sought to determine the relationship between arterial PCO2,
      CO2 chemoresponsiveness, and ventilation during exercise in healthy children and
      children with cystic fibrosis (CF). In the first part, we measured the
      hypercapnic ventilatory response (HCVR) in 16 healthy children and 16 patients
      with CF, and compared HCVR with the ventilatory response to progressive exercise
      (delta VE/delta VCO2). In the second part, we assessed the relation between age,
      the ventilatory equivalent for CO2 (VE/VCO2), and arterialized capillary PCO2
      (PaCO2), during exercise in 28 healthy children and 23 children with CF. The HCVR
      showed an age-related decline in both healthy controls and CF subjects. In
      addition, there was a correlation between forced expiratory flow from 25 to 75%
      of forced vital capacity and the HCVR, regardless of age. In controls, but not in
      CF, there was also a decline in delta VE/delta VCO2 with increasing age; and
      there was a significant correlation between delta VE/delta VCO2 and HCVR.
      Findings in the second part were similar, with a significant inverse correlation
      between age and VE/VCO2 during steady state exercise only in healthy controls.
      However, when physiologic dead space was taken into account, both CF and healthy
      control children showed a significant decline in VA/VCO2 with age. When all
      subjects were grouped together, there was a statistically significant correlation
      between PaCO2 and age, such that younger subjects had lower PaCO2 than older
      subjects. Age and PaCO2 together accounted for 71% of the variance in VA/VCO2. We
      conclude that younger children ventilate proportionately more on exercise than
      older children because they regulate PaCO2 about a lower set point. As the
      ventilatory response to exercise is significantly correlated with the HCVR, and
      the latter can be reduced in the presence of airways obstruction, an innately low
      HCVR could permit the development of exertional hypercapnia in some CF patients
      with advancing pulmonary disease.

PMID- 8865293
TI  - What are illusions?

PMID- 8865295
TI  - Evidence of a global oblique effect in human extrafoveal vision.
AB  - Analysis of recently published human contrast-sensitivity data obtained along the
      cardinal and major oblique visual-field meridians of a single subject has
      demonstrated a consistently greater sensitivity at a given eccentricity to
      horizontally oriented as compared with obliquely oriented gratings. This
      difference was evident not only at foveal but also at several eccentric loci over
      a range of low to medium spatial frequencies. This observation is to be
      distinguished in extrafoveal fixation from the well-documented oblique effect,
      which describes the variation in sensitivity with orientation at a single visual
      field locus. With periodic stimuli which were well localised in space and
      frequency, and had comparable spatial-summation properties, a spatial-frequency
      dependency of what could be termed the global oblique effect could be
      demonstrated along isoeccentric contours centred on the fovea (eccentricity 0
      deg) out to an eccentricity of at least 40 deg.

PMID- 8865294
TI  - Temporal-contrast discrimination and its neural correlates.
AB  - Reported differences in neuronal contrast processing between the parallel
      magnocellular (M) and parvocellular (P) visual pathways invite the hypothesis
      that contrast discrimination in the human visual system is more sensitive at low
      contrasts and less sensitive at high contrasts, for stimuli modulated at high
      compared with low temporal frequencies. In the present study, an edgeless
      temporally modulated uniform field was selected as the stimulus for
      psychophysical contrast discrimination, and contrast-increment thresholds for
      pedestal contrasts ranging from 5.5% to 78.2% were determined with a temporal two
      alternative forced-choice staircase procedure. The increment thresholds for five
      normal subjects were adequately fit by power functions with exponents that
      shifted continuously from about 0.5 (square-root-law behavior) to about 1.0
      (Weber's-law behavior) as stimulus temporal frequency increased from 1 to 30 Hz.
      A neural simulation, with the use of published contrast-response functions of
      magnocellular and parvocellular neurons, adjusted with an estimate of response
      variance, produced two distinct 'neural increment-threshold functions' that were
      similar to the psychophysical results obtained at the highest and the lowest
      temporal frequencies, respectively. A shift from a relatively more noise-limited
      neural mechanism to one whose response is predominantly determined by gain is
      suggested to account for the change of the contrast-increment-threshold function
      with increasing temporal frequency.

PMID- 8865296
TI  - Accuracy of reproducing angles: is a right angle special?
AB  - The ability to set the angle of a 'V' to a designated value in the following
      three conditions was compared: (1) verbal designation of V angle; (2) initial 30
      s visual demonstration of the designated V angle; (3) verbal designation of V
      angle plus feedback after every setting. The designated angles were 90 degrees
      and 45 degrees plus three arbitrary angles (65 degrees, 125 degrees, and 145
      degrees). Each run comprised thirty consecutive settings. To ensure that our
      observers based their settings entirely on V angle it was arranged that line
      orientation did not provide a reliable cue to V angle. In condition (1), accuracy
      of setting V angle was significantly worse when the designated angle was other
      than 90 degrees or 45 degrees. This was not the case in condition (2), indicating
      that observers maintained a memory of the initial demonstration throughout a run
      of thirty settings. Setting error was not significant in condition (3) for any of
      the five angles. However, even in condition (3), setting-to-setting variability
      was significantly lower for the 90 degrees angle than for the other angles.

PMID- 8865297
TI  - Cortical dynamics of boundary segmentation and reset: persistence, afterimages,
      and residual traces.
AB  - In previous work with a neural-network model of boundary segmentation and reset,
      the percept of persistence was linked to the duration of a boundary segmentation
      after stimulus offset. In particular, the model simulated the decrease of
      persistence duration with an increase in stimulus duration and luminance. Further
      evidence is revealed for the neural mechanisms involved in the theory.
      Simulations show that the model reset signals generate orientational afterimages,
      such as the MacKay effect, when the reset signals can be grouped by a subsequent
      boundary segmentation that generates illusory contours through them. Simulations
      also show that the same mechanisms explain properties of residual traces, which
      increase in duration with stimulus duration and luminance. The model hereby
      discloses previously unsuspected mechanistic links between data about persistence
      and afterimages, and helps to clarify the sometimes controversial issues
      surrounding distinctions between persistence, residual traces, and afterimages.

PMID- 8865298
TI  - Is there dissociation of perceptual and motor responses to figural illusions?
AB  - Open-loop reaching for locations within figural illusions was measured in three
      experiments. The experiments differed with respect to whether subjects were
      provided a visible target toward which to direct their reaching or were required
      to form a mental representation of the intended target. In the first experiment,
      subjects' reaching errors for vertices of a Muller-Lyer figure were similar to
      those for a nonillusory control stimulus. In experiment 2, subjects' errors while
      reaching to the imaginary bisector of the Judd illusion were consistent with the
      presence of an illusion of bisector location. However, when a bisector line was
      added to the Judd figure, reaching errors were similar to those obtained with a
      control figure. In experiment 3, subjects' open-loop reaching at the perceived
      midpoint of a triangle was biased toward its illusory perceptual midpoint. When a
      mark was placed at the midpoint between a vertex and the opposite side, reaching
      errors were similar to those obtained with a control figure. The results of the
      experiments indicate that hand-eye coordination is biased in the direction of
      illusions of bisector location only when no target is present at the intended
      goal of the reaching response and subjects are required instead to form a mental
      image of the target. Under these conditions, reaching responses appear to utilize
      the spatial map of the visual system, and are influenced by figural illusions of
      bisector location. The present data can be understood without invoking the notion
      of visual-motor dissociation.

PMID- 8865299
TI  - Is judging time-to-contact based on 'tau'?
AB  - An investigation was undertaken into whether judgments of time-to-contact between
      a laterally moving object and a bar are based on the direct perception of an
      optical variable (tau), or on the ratio between the perceived distance and
      perceived velocity of the object. A moving background was used to induce changes
      in the perceived velocities without changing the optical variables that specify
      time-to-contact. Background motion induced large systematic errors in the
      estimated time-to-contact. It is concluded that the judgment of time-to-contact
      is primarily based on the ratio between the perceived distance and the perceived
      velocity, and not on tau.

PMID- 8865300
TI  - Nonspatial visual attention explained by spatial attention plus limited storage.
AB  - The use of nonspatial attentional mechanisms in search tasks was investigated by
      presenting observers with stimuli that contained 4-12 elements located on a
      circle around the fixation point. The elements differed in one of six nonspatial
      'dimensions', namely orientation, contrast, scale, number of cycles, 'shape', and
      place in the alphabet. The target element of the search task differed from trial
      to trial but was always presented to the observer as a nonspatial, visual cue.
      This cue was displayed either before the stimulus (precue) or after the stimulus
      (postcue). Whereas a precue creates optimal conditions for the use of nonspatial
      attentional mechanisms, a postcue precludes benefits from their use. The fact
      that performance was better in the case of precued stimuli than in the case of
      postcued stimuli indicates that observers employed nonspatial attentional
      mechanisms. In the final analysis, however, the effect of nonspatial attention
      reduces to spatial attention in combination with limited storage capacity.

PMID- 8865301
TI  - Spectrum analysis, aliasing, and the perception of musical tones.
AB  - A signal-processing model is proposed in which the phenomenon of 'aliasing' is
      invoked to explain certain phenomena in the perception of musical tones, for
      which a really satisfactory explanation has not hitherto been available. It is
      shown that this model offers a reason why the harmonic series appears to play
      such a central role in tone and pitch perception, and can throw light on 'virtual
      pitch', 'harmonic beats', etc. Some preliminary results from a computer
      simulation of the model are described which are consistent with empirical data on
      tone perception.

PMID- 8865302
TI  - Natural products as a resource for new drugs.
AB  - Natural products have served as a major source of drugs for centuries, and about
      half of the pharmaceuticals in use today are derived from natural products. The
      aim of this review is to provide an overview of the continuing central role of
      natural products in the discovery and development of new pharmaceuticals. In this
      context, selected examples of important natural product-derived drugs are cited,
      focusing on some of the most recent introductions to the clinical setting, and a
      brief overview of some of the important recent developments and remaining
      challenges in the process of discovering and developing bioactive natural
      products is provided. Interest in natural products research is strong and can be
      attributed to several factors, including unmet therapeutic needs, the remarkable
      diversity of both chemical structures and biological activities of naturally
      occurring secondary metabolites, the utility of bioactive natural products as
      biochemical and molecular probes, the development of novel and sensitive
      techniques to detect biologically active natural products, improved techniques to
      isolate, purify, and structurally characterize these active constituents, and
      advances in solving the demand for supply of complex natural products.
      Opportunities for multidisciplinary research that joins the forces of natural
      products chemistry, molecular and cellular biology, synthetic and analytical
      chemistry, biochemistry, and pharmacology to exploit the vast diversity of
      chemical structures and biological activities of natural products are discussed.

PMID- 8865303
TI  - Solid-state stability of human insulin. I. Mechanism and the effect of water on
      the kinetics of degradation in lyophiles from pH 2-5 solutions.
AB  - PURPOSE: Previous studies have established that in aqueous solution at low pH
      human insulin decomposition proceeds through a cyclic anhydride intermediate
      leading to the formation of both deamidated and covalent dimer products. This
      study examines the mechanism and kinetics of insulin degradation in the amorphous
      solid state (lyophilized powders) as a function of water content over a similar
      pH range. METHODS: Solutions of 1.0 mg/mL insulin were adjusted to pH 2-5 using
      HCl, freeze-dried, then exposed to various relative humidities at 35 degrees C.
      The water content within the powders was determined by Karl Fischer titration,
      and the concentrations of insulin and its degradation products were determined by
      HPLC. Degradation kinetics were determined by both the initial rates of product
      formation and insulin disappearance. RESULTS: Semi-logarithmic plots of insulin
      remaining in lyophilized powders versus time were non-linear, asymptotically
      approaching non-zero apparent plateau values, mathematically describable by a
      reversible, first-order kinetic model. The rate of degradation of insulin in the
      solid state was observed to increase with decreasing apparent pH ('pH') yielding,
      at any given water content, solid-state 'pH'-rate profiles parallel to the
      solution pH-rate profile. This 'pH' dependence could be accounted for in terms of
      the fraction of the insulin A21 carboxyl in its neutral form, with an apparent
      pKa of approximately 4, independent of water content. Aniline trapping studies
      established that the mechanism of degradation of human insulin in lyophilized
      powders between pH 3-5 and at 35 degrees C involves rate-limiting intramolecular
      nucleophilic attack of the AsnA21 C-terminal carboxylic acid onto the side-chain
      amide carbonyl to form a reactive cyclic anhydride intermediate, which further
      reacts with either water or an N-terminal primary amino group (e.g., PheB1 and
      GlyA1) of another insulin molecule to generate either deamidated insulin (AspA21)
      or an amide-linked covalent dimer (e.g., [AspA21-PheB1] or [AspA21-GlyA1]),
      respectively. The rate of insulin degradation in lyophilized powders at 35
      degrees C increases with water content at levels of hydration well below the
      suspected glass transition and approaches the rate in solution at or near the
      water content (20-50%) required to induce a glass transition. CONCLUSIONS: The
      decomposition of human insulin in lyophilized powders between pH 3-5 is a water
      induced solid-state reaction accelerated by the plasticization effect of sorbed
      water. The formation of the cyclic anhydride intermediate at A21 occurs readily
      even in the glassy state, presumably due to the conformational flexibility of the
      A21 segment even under conditions in which the insulin molecules as a whole are
      largely immobile.

PMID- 8865304
TI  - Zinc uptake in five sectors of the rat gastrointestinal tract: kinetic study in
      the whole colon.
AB  - PURPOSE: The uptake of zinc as acexamic acid salt in the rat gastrointestinal
      tract, using an in situ static technique, was studied. Our aim was to investigate
      an absorption window for zinc and the uptake kinetics in the colon. METHODS: To
      detect selectivity phenomena in zinc absorption, buffered saline solutions of
      zinc (50 micrograms/ ml) were perfused in stomach, whole colon and three 33-cm
      fractions of the small intestine (proximal, middle and distal segments). To
      characterize zinc uptake kinetics in whole colon, five different zinc
      concentrations (5, 25, 50, 150 y 250 micrograms/ml) were assayed. Zinc secreted
      into the gastrointestinal tract during the experiments was deducted from the
      uptake. RESULTS: Zinc secretion was characterized as an apparent zero-order
      process for all the studied segments (mean secretion rate = 0.10 +/- 0.03
      microgram/(ml x min)). The stomach exhibited little ability to absorb zinc
      (apparent first order rate constant = 0.17 +/- 0.07 h-1), whereas the highest
      transport rates were found in the last two thirds of the small intestine and
      colon (first order constants: 0.66 +/- 0.13 h-1, 1.00 +/- 0.06 h-1, 0.97 +/- 0.14
      h-1, 0.96 +/- 0.19 h-1 for proximal, middle, distal and colon segments,
      respectively). Zinc uptake in the colon was characterized by means of a Michaelis
      Menten and first-order combined kinetics, with the following parameters: Vm =
      0.36 +/- 0.02 microgram/(ml x min), Km = 18.01 +/- 0.40 microgram /ml and Ka =
      0.40 +/- 0.01 h-1. CONCLUSIONS: Zinc is preferably absorbed in the middle and
      distal parts of the rat gastrointestinal tract. In the colon a saturable
      mechanism may be involved in apparent absorption.

PMID- 8865305
TI  - Stratum corneum lipids of human epidermal keratinocyte air-liquid cultures:
      implications for barrier function.
AB  - PURPOSE: The purpose of this study is to investigate the permeability barrier,
      i.e., the stratum corneum (SC) lipids, of human epidermal keratinocyte air-liquid
      cultures and compare them with those of human SC. METHOD: The SC lipids
      composition was analyzed by TLC technique, the organization by electron
      microscopic procedure, and the phase transition temperature by infrared
      spectroscopic method. RESULTS: Electron microscopy demonstrated that The SC
      lipids of cultures were largely retained inside the comeocytes, and that the
      intercellular lipids lack both the basic unit repetition (i.e., broad: narrow:
      broad: broad: narrow: broad of electron lucent bands) and the covalently-bound
      lipid envelope normally found in human SC. These characteristics are similar to
      those found in SC from patients with atopic dermatitis or psoriasis, or from
      animals with essential fatty acid deficiency, suggesting that the cultures may be
      hyperproliferative. In addition, the high free sterol content and the altered
      fatty acid/ceramide composition of these cultures argue that the compromised
      barrier function is linked to hyperproliferation and lipid synthesis, or vice
      versa. Infrared spectroscopic analyses confirm that there are major
      conformational differences between the lipids of human and cultured SC.
      CONCLUSIONS: The profound differences in SC lipid composition, organization and
      conformational properties attest that permeability alone is not a sufficiently
      sensitive marker to define barrier equivalence between cultures and human skin.

PMID- 8865307
TI  - Characterization of interactions between bile salts and drugs by micellar
      electrokinetic capillary chromatography. Part I.
AB  - PURPOSE: The general properties of micellar electrokinetic capillary
      chromatography (MECC) were utilized to characterize the strength of interactions
      between bile salts and biological active substances. METHODS: For that purpose
      various bile salts were used as micellar pseudostationary phase in the background
      electrolyte. Furthermore, a physicochemical model was applied and the effective
      partition coefficients between micellar and water phase were calculated in order
      to evaluate the strength of interactions between bile acids and the drugs.
      RESULTS: It was found that the interactions between the selected drugs and bile
      salts depend both on the lipohilicity of the drugs and on the charge of the
      components. Only hydrophobic, cationic drugs such as quinine and propranolol are
      able to interact with these surface active agents. CONCLUSIONS: MECC is a
      valuable method to characterize interactions such occurring between drugs and
      bile salts.

PMID- 8865306
TI  - The influence of an electric field on ion and water accessibility to stratum
      corneum lipid lamellae.
AB  - PURPOSE: To study ion transport through stratum corneum (SC) lipid lamellae under
      passive and iontophoretic conditions. METHODS: Iodide ion transport was measured
      by fluorescence quenching. Since the process involves diffusion of an iodide ion
      to the fluorophore located within the SC lamellae, the accessibility of iodide
      ions was measured. Moreover, the use of anthroyloxy fatty acid probes, provided
      information as a function of depth within the lamellae. RESULTS: Fluorescence
      quenching by iodide ions increased with iontophoretic current density, suggesting
      increased ion accessibility within the SC lamellae. In addition, at constant
      current, quenching decreased as the fluorophore was located deeper within the
      lamellae. This gradient in ion accessibility suggests that more iodide is found
      near the head-group than near the core of the SC lipid lamellae. Results obtained
      in the absence of iodide also show increased water accessibility during
      iontophoresis. CONCLUSIONS: These results show that in the presence of an applied
      electric field the SC lipid lamellae interior becomes more accessible to water
      and ions. These results imply that during iontophoresis, ion and water transport
      through human skin is associated, at least in part, with the SC lipid lamellae.

PMID- 8865308
TI  - Dielectric analysis of phosphorylcholine head group mobility in egg lecithin
      liposomes.
AB  - PURPOSE: A knowledge of the interfacial properties of lecithin underpins our
      understanding of many of the physicochemical characteristics of drug delivery
      systems such as liposomes and lecithin stabilized microemulsions. In order to
      further this understanding, a high frequency dielectric study of the interfacial
      properties of egg lecithin liposomes was undertaken. METHODS: The effect of
      temperature, lecithin concentration and probe sonication on the interfacial
      dielectric properties of liposomal suspensions was investigated by high frequency
      dielectric relaxation spectroscopy between 0.2-6 GHz. RESULTS: The frequency
      dependent permittivity of each suspension exhibited a dielectric dispersion
      centred around 100 MHz, corresponding to the relaxation of zwitterionic head
      groups. The activation energy for head group reorientation was estimated as delta
      H = 6.3 kJ mol-1. There was an increase in extent of inter-head group
      interactions on increasing the liposome volume fraction, whereas the effect of
      probe sonication showed that: (i) head groups in both the outer and inner
      lamellae contribute to the dielectric response; (ii) the head groups may be less
      restricted in liposomes of high surface curvature with few lamellae; (iii) the
      high frequency permittivity of the suspension increased on sonication, as a
      result of a reduction in the amount of (depolarized) interlamellar water
      following a reduction in the number of lamellae per liposome. CONCLUSIONS:
      Dielectric analysis of the zwitterionic head groups of lecithin therefore
      provides a means for investigating the surface of lecithin liposomes, and may be
      used to investigate the effect of drugs and other solutes on membranes.

PMID- 8865309
TI  - Insight into the lipophilicity of the aromatic N-oxide moiety.
AB  - PURPOSE: A systematic study to assess the influence of N-oxygenation on the
      lipophilicity of aromatic weak bases was performed. METHODS: The methods used
      were experimental (CPC and shake-flask techniques) and computational (AMI semi
      empirical method). RESULTS: The intrinsic increment in the log P(oct) system for
      an oxygen atom added to form an aromatic N-oxide, designated as diff(log PN(O) 
      N), was -1.91, but the presence of para-substituents markedly affected this
      value. The good linear relationship (r2 = 0.92) between diff(log PN(O) - N), and
      the electronic density on the oxygen atom suggests that H-bond acceptor basicity
      is the main structural factor responsible for the variations in lipophilicity of
      aromatic N-oxides. Partition coefficients of aromatic N-oxides in dodecane/buffer
      and chloroform/buffer systems also support this hypothesis. CONCLUSIONS: The
      solvent-dependent polarity of the N-oxide moiety is mainly due to its marked H
      bond acceptor basicity.

PMID- 8865310
TI  - Correlation of physiochemical parameters to the hydrophobic contribution
      constants of amino acid residues in small peptides.
AB  - PURPOSE: This paper attempts to correlate the hydrophobic contribution constants
      (faa) of 21 amino acids in small peptides with commonly used physiochemical
      parameters. These faa constants can then be used to predict hydrophobicity change
      in peptides when any one of the amino acid residue is substituted with another.
      METHOD: Non-weighted least squares method was used in deriving regression
      equations with a BMDP program. A Hyperchem program for Windows was used to
      calculate the group dipole moments of the side chain. RESULTS: A good correlation
      (r = 0.97) was obtained using a four parameter equation including molecular
      weight (log MW), hydrogen bond forming ability (HB), dipole moment (mu) and an
      indicator variable (I) to account for the presence of a free primary amine group
      in the side chain. CONCLUSIONS: This proposed model should be useful in
      predicting the hydrophobic contribution constants of other uncommon amino acids
      and in the estimation of log P'values of numerous peptides containing different
      possible combinations of these amino acids, as well as log P' values resulting
      from amino acid substitution as is done in site-directed mutagenesis.

PMID- 8865311
TI  - Immunostimulating polysaccharides from Panax notoginseng.
AB  - PURPOSE: The main purpose of this study is to prepare and characterize
      polysaccharides from Panax notoginseng, investigate their effects on immune
      system in vitro in order to find new immunostimulants for the prevention and
      supporting treatment of infection and immunodeficiency related diseases. METHODS:
      Polysaccharides were extracted with aqueous solution, separated with column
      chromatography. Their anticomplementary activities were investigated by using
      human serum and antibody-sensitized sheep red blood cells. Interferon-gamma and
      tumor necrosis factor inductive activities were studied by using isolated mouse
      spleen lymphocytes and peritoneal macrophages, respectively. RESULTS: Four
      polysaccharides, homogeneous in gel-filtration chromatography, were prepared and
      designated PF3111, PF3112, PBGA11, and PBGA12. Component sugar analysis revealed
      that they are heteroglycans with MWs ranging from 37 kD to 760 kD, composed of
      glucose, galactose, arabinose, mannose, and xylose in different molar ratios.
      Fraction PBGA12 has the most anticomplementary activity which is mediated through
      both alternative and classical pathways. All the polysaccharides except PBGA11
      induced the production of interferon-gamma in the presence of concanavalin A.
      They induced the production of significant amount of TNF-alpha in cell cultures.
      CONCLUSIONS: The polysaccharides from P.notoginseng have immunostimulating
      activities in vitro.

PMID- 8865312
TI  - Local absorption kinetics of levofloxacin from intestinal tract into portal vein
      in conscious rat using portal-venous concentration difference.
AB  - PURPOSE: The local absorption kinetics of levofloxacin from the intestinal tract
      was quantitatively evaluated by simultaneously measuring the portal and venous
      plasma concentrations in a conscious rat. METHODS: The venous and upper portal
      blood vessels were cannulated through the jugular and pyloric veins,
      respectively. After oral or intravenous administration of levofloxacin, portal
      and venous concentrations of levofloxacin were simultaneously monitored. The
      absorption rate from the intestine into the portal system was calculated from the
      portal-venous difference in the plasma concentration of levofloxacin, considering
      the distribution of levofloxacin into erythrocytes. Portal blood flow rate was
      newly measured by an electromagnetic flow meter. RESULTS: There was little portal
      venous difference after an intravenous dose of levofloxacin. In contrast, after
      oral administration, the plasma concentration in the portal vein was constantly
      higher than that in the jugular vein, demonstrating that this difference was
      caused by the intestinal absorption of levofloxacin. CONCLUSIONS: Approximately
      90% levofloxacin was absorbed as the intact form from the intestinal tract into
      the portal system. By considering the bioavailability of levofloxacin in rat, the
      hepatic extraction ratio in vivo of levofloxacin was estimated to be 30%. The
      mean local absorption time (Ta) was 1.44 hr which coincided almost with the mean
      absorption time (MAT).

PMID- 8865313
TI  - The effect of size on uptake of orally administered latex microparticles in the
      small intestine and transport to mesenteric lymph nodes.
AB  - PURPOSE: The present study examines the relationship between size and particle
      transit across the mucosal barrier of the gastrointestinal tract to other sites
      of the body. The extent of particle uptake with increasing size, the tissue
      distribution and cut-off points for 2-20 microns particles is investigated.
      METHODS: An established fluorescent latex particle-young adult rat model is used
      and particle numbers in small intestine and mesenteric lymph nodes, 0.5 h post
      administration, counted by fluorescence microscopy in bulk tissue specimens and
      cryosections. RESULTS: Bulk tissue analysis provides evidence for the presence of
      particles of all sizes in the Peyer's patch regions, but only for 2 microns
      particles in the nodal tissues. Microscopy establishes uptake of both 2 and 6
      microns particles in most intestinal and nodal tissue sites and compartments. By
      contrast, uptake of the larger particles is much reduced. CONCLUSIONS: Although
      more of the smaller (2 microns) particles are taken up, particularly by
      epithelial tissues, the 6 microns size appears more efficient in terms of volume
      translocated to lymph nodes. This could have implications in the therapeutic use
      of particles for drug and vaccine delivery and for radiation safety.

PMID- 8865314
TI  - Pectin/ethylcellulose film coating formulations for colonic drug delivery.
AB  - PURPOSE: The purpose of the study was to investigate the potential of pectin,
      ethylcellulose combinations as a practical film coating for colonic delivery.
      METHODS: Combinations of pectin and ethylcellulose, in the form of an aqueous
      dispersion, were used as coating formulations. Paracetamol cores were used as the
      substrate. The coatings were assessed by a flow through dissolution system
      simulating in vivo conditions by changes in pH and residence time. Pectinolytic
      enzymes were used to simulate the bacterial flora of the colon. RESULTS: Drug
      release was controlled by the ratio of ethylcellulose to pectin in the film coat.
      Increasing the proportion of ethylcellulose and increasing the coat weight
      reduced drug release in pH1 and pH7.4 media. The addition of pectinolytic enzymes
      to pH6 media increased the release of drug. CONCLUSIONS: Combinations of
      ethylcellulose and pectin can provide protection to a drug in the upper g.i.
      tract while allowing enzymatic breakdown and drug release in the colon.

PMID- 8865315
TI  - Metabolism, uptake, and transepithelial transport of the diastereomers of Val-Val
      in the human intestinal cell line, Caco-2.
AB  - PURPOSE: The purpose of this study was to determine whether the binding of the
      diastereomers of Val-Val to the apical oligopeptide transporter(s) could be
      correlated with their cellular uptake and transepithelial transport. METHODS: The
      Caco-2 cell culture system was used for all experiments. The binding of the
      diastereomers of Val-Val was evaluated by determining their ability to inhibit
      [3H]cephalexin uptake. The stability of the diastereomers was determined in a
      homogenate of Caco-2 cells and in the apical bathing solution over Caco-2 cell
      monolayers. The cellular uptake and transepithelial transport properties of the
      individual diastereomers were studied using Caco-2 cell monolayers. RESULTS: 10
      mM concentrations of L-Val-L-Val, L-Val-D-Val, D-Val-L-Val and D-Val-D-Val
      inhibited cellular uptake of [3H]cephalexin (0.1 mM) by 92%, 37%, 70%, and 18%,
      respectively. When the cellular uptake of Val-Val diastereomers (1 mM) were
      evaluated, the intracellular concentrations of L-Val-D-Val and D-Val-L-Val were
      15 and 50 times higher, respectively, than that of D-Val-D-Val. The cellular
      uptake of L-Val-D-Val and D-Val-L-Val was inhibited by Gly-Pro (10 mM) ( > 95%),
      whereas Gly-Pro had no effect on the cellular uptake of D-Val-D-Val. L-Val-L-Val
      was not detected in the Caco-2 cells, probably due to its metabolic lability.
      When the transepithelial transport of the Val-Val diastereomers (1 mM) was
      determined, L-Val-D-Val, D-Val-L-Val and D-Val-D-Val transport rates were
      similar. The transepithelial transport of L-Val-D-Val and D-Val-L-Val was
      inhibited by Gly-Pro (10 mM) 36% and 30%, respectively, while Gly-Pro inhibited
      carnosine (1 mM) transepithelial transport by 65%. Gly-Pro had no effect on the
      transepithelial transport of D-Val-D-Val. CONCLUSIONS: These results suggest that
      the major transepithelial transport route of L-Val-D-Val, D-Val-L-Val and D-Val-D
      Val is passive diffusion via the paracellular route. The binding of Val-Val
      diastereomers to the oligopeptide transporter(s) is a good predictor of their
      cellular uptake, however, the binding is not a good predictor of their
      transepithelial transport. It appears that the stereochemical requirements for
      the transporter that mediates efflux of the peptide across the basolateral
      membrane may be different from the requirements for the apical transporter that
      mediates cellular uptake.

PMID- 8865316
TI  - Effects of permeation enhancers on the transport of a peptidomimetic thrombin
      inhibitor (CRC 220) in a human intestinal cell line (Caco-2).
AB  - PURPOSE: The effects of five different permeation enhancer systems on the
      transport properties of a peptidomimetic thrombin inhibitor. CRC 220, were
      investigated in monolayers of a human intestinal cell line (Caco-2). METHODS: The
      transepithelial transport rates and additionally the cytotoxic properties of
      these enhancers were characterized using the following tests: measurement of the
      transepithelial electrical resistance (TEER), the MTT-transformation, the protein
      content and the release of cytosolic lactate dehydrogenase (LDH), as well as FITC
      phalloidin and propidium iodide staining. RESULTS: All permeation enhancer
      systems showed concentration-dependent effects on cell permeability and toxicity.
      The most prominent effects on peptide transport were seen at the highest
      concentration (40 mM), yielding the rank order, NaTC > NaTC/Cholesterol > Solulan
      C24 > NaTC/Oleic acid > NaTC/PC18. Using the TEER after 120 min exposure as the
      most sensitive parameter describing cytotoxicity, the following order was
      obtained: Solulan C24 > NaTC > NaTC/PC18 = NaTC/Cholesterol > NaTC/Oleic acid >
      NaTC/PC. Generally, efficient enhancement of peptide transport was associated
      with a noticeable influence on cell viability under in-vitro conditions.
      CONCLUSIONS: Taking into account permeation and cytotoxicity as a function of
      concentration, both NaTC at 15 mM and the mixed micellar system NaTC/oleic acid
      at 0.75 mM offer interesting enhancement properties, showing an 18-fold increase
      in CRC 220 transport rates. The effects on cell viability and cytotoxicity were
      comparatively low and of reversible nature.

PMID- 8865317
TI  - Buccal absorption of testosterone and its esters using a bioadhesive tablet in
      dogs.
AB  - PURPOSE: As the oral bioavailability of testosterone is very low because of its
      high first pass effect, buccal administration might present a viable alternative.
      In this study a buccal bioadhesive tablet was used in order to sustain the
      delivery and bypass the liver. METHODS: Testosterone and testosterone acetate,
      propionate, enanthate and decanoate were investigated. The influence of the
      concentration of testosterone (10-50%) and testosterone esters (30%) on in vitro
      bioadhesion was investigated. The absolute (i.v.) and relative (oral)
      bioavailability of 60 mg testosterone or an equivalent amount of testosterone
      ester was determined in castrated male dogs. RESULTS: Both the in vitro
      detachment force and the work of adhesion decreased gradually with an increasing
      amount of testosterone and for an increasing chain length of the esters, except
      in the case of testosterone enanthate. The in vivo results revealed that the
      bioavailability of testosterone was significantly higher (p < 0.05) than that of
      the esters, which is probably due to the lower solubility of the esters. The mean
      absolute bioavailability of testosterone from the bioadhesive tablet was 14.1%,
      while the mean relative bioavailability was 1370%. The buccal administration of
      testosterone via the bioadhesive tablet allowed the maintenance of the plasma
      level at above 3 ng/ml for 15 to 24 h. CONCLUSIONS: Buccal absorption of
      testosterone was significantly higher than that of its esters.

PMID- 8865318
TI  - In vivo buccal delivery of the peptide drug buserelin with glycodeoxycholate as
      an absorption enhancer in pigs.
AB  - PURPOSE: To study the potential of buccal delivery of the peptide drug in pigs.
      METHODS: Intravenous administration and buccal delivery without and with 10 mM
      sodium glycodeoxycholate (GDC) as absorption enhancer were investigated as a
      randomised cross-over study in six pigs. The buccal delivery device consisted of
      an application chamber with a solution of buserelin and was attached to the
      buccal mucosa for 4 hours using an adhesive patch. RESULTS: Buccal administration
      of buserelin resulted in rapidly reached steady state plasma levels. The absolute
      bioavailability of the peptide after buccal delivery for 4 hours could be
      increased from 1.0 +/- 0.3 to 5.3 +/- 1.1% (mean +/- SD.) by co-administration of
      10 mM GDC (0.45% w/v)). CONCLUSIONS: The results of this study demonstrate that
      buccal administration with the use of absorption enhancers is a useful approach
      for the delivery of peptide drugs such as buserelin.

PMID- 8865319
TI  - Nitric oxide (NO)-releasing pathway of FK409 in the presence of sulfhydryl
      bearing compounds.
AB  - PURPOSE: We have recently reported that degradation of FK409 with generation of
      NO is spontaneous and is accelerated in the presence of sulfhydryl-bearing
      compounds, such as L-cysteine (Cys) and glutathione (GSH). The purpose of the
      present study is to investigate the NO-releasing pathway of FK409 in the presence
      of sulfhydryl-bearing compounds. METHODS: The degradation process of FK409 in the
      presence of Cys or GSH was investigated by means of 1H-nuclear magnetic resonance
      (NMR) spectroscopy and high-performance liquid chromatography (HPLC). RESULTS:
      The degradation of FK409 in the presence of Cys was dependent on concentration of
      Cys, and showed pH-dependency, accelerating with an increase in pH. The 1H-NMR
      spectra of FK409 with Cys suggested that time-dependent elimination of the
      hydrogen atom at the alpha-position of the nitro moiety (5-position) was
      accelerated by Cys in weakly alkaline solution. Cys and GSH were transformed
      readily, concomitant with FK409 degradation, to give their oxidized forms and
      probably S-nitrosothiols. CONCLUSION: The effect of sulfhydryl-bearing compounds
      on FK409 degradation is due to the acceleration of deprotonation of the hydrogen
      atom at the 5-position by thiolate anion as well as hydroxyl ion. Sulfhydryl
      bearing compounds reacted with the released NO resulting in formation of
      disulfides via intermediate S-nitrosothiols.

PMID- 8865320
TI  - Glucuronidation metabolic kinetics of valproate in guinea pigs: nonlinear at
      clinical concentration levels.
AB  - PURPOSE: Nonlinear conjugation metabolic rate of valproic acid (VPA) has been
      speculated previously from plasma elimination and liver concentration of VPA in
      guinea pigs. The purposes of the present study were to assess our speculation by
      direct measurement of VPA glucuronidation rate in vitro. METHODS: VPA at various
      concentrations (10-200 micrograms/ml) was incubated with guinea-pig liver
      homogenate, mitochondria or microsome in the presence of cofactor, uridine 5'
      diphosphoglucuronic acid (UDPGA). The maximum glucuronidation rate (Vmax) and
      Michaelis-Menten constant (Km) of VPA were determined. RESULTS: On a body weight
      basis, the Vmax and the Km values of VPA glucuronidation estimated from liver
      homogenate were 1.8 mumol/min/kg and 0.3 mumol/ml, respectively; and that from
      microsome suspension were 1.2 mumol/min/kg and 0.16 mumol/ml, respectively. These
      data are comparable with the primary metabolic parameters observed from previous
      in vivo study. The glucuronidation clearance calculated from these parameters was
      0.10-0.48 fraction of total clearance, which was in agreement with the reported
      data observed from clinical and animal urinary recoveries of VPA-G. The
      glucuronidation reaction was not detectable in mitochondria suspension.
      CONCLUSIONS: The glucuronidation kinetics of VPA is nonlinear and saturable
      within clinical concentration range. Estimation of in vivo VPA glucuronidation
      kinetics from in vitro kinetic parameters is feasible.

PMID- 8865321
TI  - Transport of drugs across the Xenopus pulmonary membrane and their absorption
      enhancement by various absorption enhancers.
AB  - PURPOSE: The permeability of drugs across the Xenopus pulmonary membrane and the
      effects of various absorption enhancers on their absorption were examined using
      an in vitro Ussing chamber technique. METHODS: Phenol red and fluorescein
      isothiocyanate-labeled dextrans (FDs) with different molecular weights were
      chosen as water-soluble model drugs. Absorption enhancers used in this study were
      N-lauryl-beta-D-maltopyranoside (LM), linoleic acid-HC060 mixed micelle (MM),
      sodium glycocholate (Na-GC), sodium caprate (Na-Cap), sodium salicylate (Na-Sal)
      and disodium EDTA (EDTA). RESULTS: The permeability of drugs gradually decreased
      with increasing their molecular weights, and the absorption of phenol red
      significantly increased by these absorption enhancers. Among these additives, LM,
      MM and Na-Cap appeared to be more effective for enhancing the permeability of
      drugs than the others. Furthermore, we plotted the logarithm of apparent
      permeability coefficient (Papp) of these drugs against the logarithm of their
      molecular weights. There exists a good correlation between these parameters. We
      measured transmembrane resistance(Rm) of Xenopus pulmonary membrane during the
      transport experiment to examine the membrane integrity. The average Rm value was
      about 700 omega.cm2, and this value was maintained for 3 hr. CONCLUSIONS: This
      method is useful for estimating the transport characteristics of drugs across the
      pulmonary membrane.

PMID- 8865322
TI  - Oxidation of human insulin-like growth factor I in formulation studies: kinetics
      of methionine oxidation in aqueous solution and in solid state.
AB  - PURPOSE: The aim of this work was to study the kinetics of oxidation of
      methionine in human Insulin-like Growth Factor I (hIGF-I)1 in aqueous solution
      and in the solid state by the aid of quantification of oxygen. METHODS: The
      oxidized from of hIGF-I was characterized by tryptic peptide analysis, RP-HPLC
      and FAB-MS and quantified by RP-HPLC. The oxygen content was quantified
      polarographically by a Clark-type electrode. RESULTS: Second-order kinetics with
      respect to amount of protein and dissolved oxygen was found to be appropriate for
      the oxidation of methionine in hIGF-I. The rate constants ranged from 1 to 280 M
      1 month-1 and had an activation energy of 95 (+/-4) kl/mole. Light exposure,
      storage temperature and oxygen content were found to have a considerable impact
      on the oxidation rates. No significant difference in reaction rates was found for
      the oxidation of hIGF-I in aqueous solution or in the solid state. A method for
      decreasing the oxygen content in aqueous solution without purging is described.
      CONCLUSIONS: Polarographic quantification of dissolved oxygen makes it possible
      to establish the kinetics for oxidation of proteins. The oxidation of methionine
      in hIGF-I appears to follow second-order kinetics.

PMID- 8865323
TI  - Excipient interaction with cetylpyridinium chloride activity in tablet based
      lozenges.
AB  - PURPOSE: The purpose of the investigation was to determine the effect of tablet
      excipients on the activity of cetylpyridinium chloride (CPC) and the relative
      interaction between excipients and CPC. METHODS: An analytical assay was
      developed to evaluate the interaction between CPC and the excipients. In vivo
      activity was investigated using six volunteers by determining the reduction in
      colony forming units recoverable from the oropharynx after sucking each
      proprietary lozenge separately on different days. In vitro determinations
      investigated the relative antimicrobial activity of aqueous solutions of the
      lozenges and, the effect of pH and tablet base excipients on that activity
      against Staphylococcus aureus, Streptococcus pyogenes and Candida albicans.
      RESULTS: Both in vivo and in vitro results showed that the tablet based lozenges
      had markedly reduced antimicrobial activities compared with previous results with
      a candy based lozenge (in vivo and in vitro) or the same concentration of aqueous
      CPC (in vitro). Magnesium stearate suspensions in CPC 250 micrograms/ml indicated
      that magnesium stearate adsorbed CPC and at 0.4% lozenge weight and above
      significantly reduced the antimicrobial activity of CPC 250 micrograms/ml.
      CONCLUSIONS: The reduced activity of CPC in tablet based lozenges resulted from a
      decreased availability of CPC in solution due to an adsorption of CPC on
      magnesium stearate. To avoid this reduction in activity tablet based lozenges
      containing CPC 250 micrograms/ml, or similar concentrations, plus magnesium
      stearate should contain not more than 0.3% w/w lozenge weight of the lubricant.

PMID- 8865324
TI  - The in vitro release of some antimuscarinic drugs from monoolein/water lyotropic
      liquid crystalline gels.
AB  - PURPOSE: To investigate the potential use of a monoolein/water lyotropic liquid
      crystalline gel for the vaginal delivery of the antimuscarinic drugs,
      propantheline bromide and oxybutynin hydrochloride to treat urinary incontinence,
      using Myverol 18-99 as a commercially available grade of monoolein. METHODS: The
      influence of propantheline bromide and oxybutynin hydrochloride on the phase
      structure of Myverol 18-99/water gels was investigated using polarising
      microscopy. The in-vitro release of the antimuscarinic drugs from Myverol 18
      99/water gels was determined and the release pattern interpreted with the aid of
      results from swelling studies and partition coefficient determinations. RESULTS:
      Myverol 18-99 forms gels with lyotropic liquid crystalline structures in the
      presence of water. The addition of propantheline bromide and oxybutynin
      hydrochloride promoted the formation of gels with a lamellar phase structure. The
      gels absorbed water at a rate inversely proportional to their initial water
      content until they reached an equilibrium water content of approximately 40% w/w
      whilst maintaining their physical integrity. The release of the antimuscarinic
      drugs was sustained over a period of approximately 18 hours and followed square
      root of time kinetics indicating that the rate of release was diffusion
      controlled. CONCLUSIONS: The in-vitro release behaviour of Myverol 18-99/water
      gels suggested that they are suitable carriers to deliver propantheline bromide
      or oxybutynin hydrochloride. The results of swelling studies indicated that a
      confined area, such as the vaginal cavity, would be a suitable site of
      administration.

PMID- 8865325
TI  - High-performance liquid chromatographic analysis of dipyrone metabolites to study
      their formation in human liver microsomes.

PMID- 8865326
TI  - Mechanisms of 5-fluorouracil (5-FU) transport in isolated rabbit choroid plexus
      tissue slices.

PMID- 8865327
TI  - Physical and nutritional qualities of extruded weaning foods containing sorghum,
      pearl millet, or finger millet blended with mung beans and nonfat dried milk.
AB  - Sorghum, pearl millet, and finger millet flours (60% of each) were blended with
      toasted mung bean flour (30%) and nonfat dry milk (10%) and extruded (Brabender
      single screw) to make precooked, ready-to-eat, weaning foods. The extruded foods
      had high cold paste viscosity, but their cooked paste viscosity was lower than
      that of the respective blends. Chemical scores of the extruded foods were 78 for
      sorghum, 80 for pearl millet, and 96 for finger millet. Protein digestibility
      corrected amino acid scores (PD-CAS) were similar for pearl millet (68%) and
      finger millet (69%); PD-CAS for sorghum was 57%. Total dietary fiber content of
      the foods ranged from 7.6 to 10.1%, with the soluble dietary fiber content of the
      foods being about 10% higher than that of the corresponding blends. Extrusion
      enhanced the in vitro protein digestibility of foods, but no marked difference
      occurred in the in vitro carbohydrate digestibility among the unprocessed blends
      and the extruded foods. The net protein ratio, protein efficiency ratio, and
      biological values were higher for the finger millet food than for the pearl
      millet food, probably because of the higher lysine content of the finger millet
      protein.

PMID- 8865328
TI  - Beta-carotene content of postharvest orange-fleshed muskmelon fruit: effect of
      cultivar, growing location and fruit size.
AB  - The influence of two growing locations (soil types), six fruit sizes, and two
      years on the postharvest Beta-carotene content of muskmelon (Cucumis melo L. var.
      reticulatus Naud.) fruit was studied with two different cultivars. Fully abscised
      commercial size fruit: 9, 12, 15, 18, 23, and 30 (fruit/0.04 M3 shipping box) had
      highly variable Beta-carotene contents (5.3 to 33.8 micrograms/g fresh weight)
      that varied by size class, soil type and cultivar. Beta-carotene content
      increased with fruit size up to a maximum, though fruit size continued to
      increase. Find sandy loam soil produced fruit with less Beta-carotene content
      than silty clay loam soil. The cultivar Primo contained higher Beta-carotene
      content levels than cultivar Cruiser. Mesocarp percent moisture content for both
      'Cruiser' and 'Primo' at both locations by fruit size was not significantly
      correlated (r = 0.40) with Beta-carotene content. Indicating fruit cell dilution
      may not contribute to the differences in Beta-carotene content in different fruit
      size classes. Beta-carotene content of size class '18' fruit from six cultivars
      grown on the silty clay loam soil for two consecutive years, showed a year, and
      year by cultivar effect for some cultivars. Whereas, some cultivars did not
      differ in Beta-carotene content between the two years. This indicates a potential
      for controlling Beta-carotene content of muskmelon fruit at a constant, high
      level by careful selection of production cultivar.

PMID- 8865329
TI  - Usage patterns and contribution of fermented foods to the nutrient intakes of low
      income households in Emene, Nigeria.
AB  - This study investigated the usage consumption pattern and chemical composition of
      fermented foods consumed in 191 rural households (1030 individuals) in Emene. The
      result showed that fermented foods were widely used and consumed by most age
      groups (under 2 years to adults) because of poor socioeconomic status.
      Fermentation period varied with type of food and was mostly carried out as a
      means of detoxifying certain foods. Generally, fermented foods contributed
      substantially to the daily caloric (46.3 to 79.9% for males and 57.5 to 78% for
      females); calcium (33.8 to 63.5% for males and 48.3 to 55.4% for females); iron
      (34.4 to 58.6% for males and 47.4 to 74.6% for females); and thiamin (23 to 58.5%
      for males and 37.5 to 60% for females) intakes. The contributions of fermented
      foods to protein (10 to 40.7%) and ascorbic acid (1.9 to 18.7%) intakes were
      however, low. When compared with the FAO recommendations, the daily intakes of
      protein, calcium, riboflavin, niacin and ascorbic acid by the subjects were low
      due to large consumption of starchy root crops. Poor financial status was the
      most limiting factor to adequate nutrient intake. Such results point out the need
      for nutrition education related to improved methods of preparation and food
      selection.

PMID- 8865330
TI  - The suitability of African bush mango juice for wine production.
AB  - A good quality wine was produced from African bush mango (Irvingia
      var.gabonensis). Analysis of the African bush mango juice showed that it
      contained 3.6% total sugar, 1.09% protein, 4.2 degrees Brix soluble solids (SS)
      0.5% ash, 50.24% total solids (TS), 66.7 mg/100 ml ascorbic acid and pH 5.12. The
      juice ameliorated to 23 degrees Brix was inoculated with 3% (w/v) Baker's yeast
      (Saccharomyces cerevisiae) and held at 30 +/- 2 degrees C for 28 days. SS and pH
      decreased while titratable acidity (TA) increased with increasing period of
      fermentation. Fermentation was 110% efficient. The wine produced had 8.12% (v/v)
      alcohol, 0.78% protein, 6.5% Brix SS, 0.64 g/100 ml TA, and a pH 3.10. Sensory
      evaluation results showed that there was no significant difference (p = 0.05) in
      colour, mouthfeel, sweetness, flavour and general acceptability, between African
      Bush mango wine and a reference wine. The wine was generally accepted.

PMID- 8865331
TI  - Effect of processing on protein digestibility, biological value and net protein
      utilization of millet and legume based infant mixes and biscuits.
AB  - Effect of combinations of millet and legume and processing on digestibility,
      biological value and net protein utilization was evaluated using albino rats. The
      millets and legumes selected for the study include sorghum, pearl millet, finger
      millet, chickpea and green gram (P radiatus). The processes tested include
      dehulling, boiling, roasting, malting and baking. Among the combinations tested,
      the sorghum-chickpea combination had significantly (p < 0.05) higher
      digestibility. Between the processes tested, roasting resulted in significantly
      higher net protein utilization. Results of biological study on biscuits prepared
      by using millet and legume combination flours, indicated the biscuits to be of
      good protein quality.

PMID- 8865332
TI  - Studies on the seed oils of Parkia biglobosa and Parkia bicolor.
AB  - The seed oils of Parkia biglobosa and Parkia bicolor (Mimosaceae) have been
      analysed for their possible edible utility and to provide some physical data on
      both oils. The fatty acid composition of the oils was identified. Six major fatty
      acids were identified in the oil of P. bicolor while five were identified in that
      of P. biglobosa by Gas Chromatography (GC) and Gas Chromatography-Mass
      Spectroscopy (GC-MS). The two oils contained five similar fatty acids in almost
      the same ratios. Arachidic acid was the most abundant fatty acids (greater than
      forty per cent) in both oils. Other fatty acids in the oils were behenic,
      stearic, palmitic and linoleic acids. The sixth fatty acid in P. bicolor was an
      odd number of carbon atom and un unsaturated fatty acid (C20H37COOH) named
      bicolargic acid. The oils were also found to be non toxic.

PMID- 8865333
TI  - Comparison of two methods for determining in vitro intestinal absorption of
      nutrients using rats fed different diets.
AB  - Absorption of sucrose, glucose, leucine and aspartate was studied using
      intestinal everted sac of rats fed on french bean diets namely PDR-14, HUR-137
      and HUR-15 using casein as a control. Absorption of nutrients was monitored
      spectrophotometrically and by 14C radio assay of metabolites using scientillation
      counting. The absorption pattern of amino acids was found to be similar but of
      glucose and sucrose differed. Glucose was found to be more absorbed than sucrose
      in spectrophotometer assay and the pattern reversed in radio assay. Absorption of
      sucrose and leucine were higher by rats fed on HUR-137 diet and similarly, more
      aspartate was absorbed when fed on HUR-15 diet as demonstrated by both the
      methods. Rats fed on HUR-137 diet exhibited higher glucose absorption as shown by
      spectrophotometric assay, but rats on HUR-15 diet by radio assay. Absorption of
      nutrients differed significantly between casein and french beans.

PMID- 8865334
TI  - Levels of antinutritional factors in pearl millet as affected by processing
      treatments and various types of fermentation.
AB  - Pearl millet (Pennisetum typhoideum) was fermented with Lactobacilli or yeasts
      alone and in combination, and with natural microflora after various processing
      treatments, as grinding, soaking, debranning, dry heat treatment, autoclaving and
      germination. Fermentation was carried out at 30 degrees C for 48 hours with
      Lactobacillus plantarum (LP) and Rhodotorula (R) isolated from naturally
      fermented pearl millet and Lactobacillus acidophilus (LA), Candida utilis (CU)
      and natural microflora (NF). Germination and autoclaving, and debranning and
      autoclaving were the most effective processing treatments to reduce the phytic
      acid, amylase inhibitors and polyphenols. There was a further reduction in these
      antinutrients due to fermentation. Phytic acid and amylase inhibitors were
      completely eliminated after fermentation in some of the samples especially in
      soaked, debranned and germinated ones. Polyphenols were altered non-significantly
      in general but fermentation with Lp + R and NF caused a significant increase in
      polyphenols.

PMID- 8865335
TI  - 1996 Johns Hopkins Protein Folding Meeting.

PMID- 8865336
TI  - Docking enzyme-inhibitor complexes using a preference-based free-energy surface.
AB  - We present a docking scheme that utilizes both a surface complementarity screen
      as well as an energetic criterion based on surface area burial. Twenty rigid
      enzyme/inhibitor complexes with known coordinate sets are arbitrarily separated
      and reassembled to an average all-atom rms (root mean square) deviation of 1.0 A
      from the native complexes. Docking is accomplished by a hierarchical search of
      geometrically compatible triplets of surface normals on each molecule. A pruned
      tree of possible bound configurations is built up using successive consideration
      of larger and larger triplets. The best scoring configurations are then passed
      through a free-energy screen where the lowest energy member is selected as the
      predicted native state. The free energy approximation is derived from
      observations of surface burial by atom pairs across the interface of known
      enzyme/inhibitor complexes. The occurrence of specific atom-atom surface burial,
      for a set of complexes with well-defined secondary structure both in the bound
      and unbound states, is parameterized to mimic the free energy of binding. The
      docking procedure guides the inhibitor into its native state using orientation
      and distance-dependent functions that reproduce the ideal model of free energies
      with an average rms deviation of 0.9 kcal/mol. For all systems studied, this
      docking procedure identifies a single, unique minimum energy configuration that
      is highly compatible with the native state.

PMID- 8865337
TI  - Is the binding of beta-amyloid protein to antichymotrypsin in Alzheimer plaques
      mediated by a beta-strand insertion?
AB  - A growing body of experimental evidence demonstrates that the serpin
      antichymotrypsin plays a regulatory role in Alzheimer plaque physiology by
      interacting with the 42 residue beta-amyloid protein, and we have used molecular
      modeling and energy minimization techniques to study this interaction. Based on
      the unique plasticity of beta-sheet elements in antichymotrypsin (as well as
      other serpins), we conclude that the interaction of the two proteins is mediated
      by insertion of the N-terminus of beta-amyloid into beta-sheet C of
      antichymotrypsin as a pseudo-strand s1C. This beta-strand insertion requires the
      displacement of native antichymotrypsin strand s1C, which is known to occur
      partially or completely at different stages of serpin function. Thus, the
      association of the two proteins in vivo may be facilitated by a particular
      functional state of the serpin, e.g., the native or protease-complexed state.

PMID- 8865338
TI  - Oxygen binding by single crystals of hemoglobin: the problem of cooperativity and
      inequivalence of alpha and beta subunits.
AB  - Oxygen binding by the human hemoglobin tetramer in the T quaternary structure is
      apparently noncooperative in the crystalline state (Hill n = 1.0), as predicted
      by the two-state allosteric model of Monod, Wyman, and Changeux (MWC) (Mozzarelli
      et al., Nature 351:416-419, 1991; Rivetti et al., Biochemistry 32:2888-2906,
      1993). However, cooperativity within the tetramer can be masked by a difference
      in affinity between the alpha and beta subunits. Indeed, analysis of the binding
      curves derived from absorption of light polarized along two different crystal
      directions, for which the projections of the alpha and beta hemes are slightly
      different, revealed an inequivalence in the intrinsic oxygen affinity of the
      alpha and beta subunits (p50(alpha) approximately 80 torr, p50(beta)
      approximately 370 torr at 15 degrees C) that compensates a small amount of
      cooperativity (Rivetti et al., Biochemistry 32:2888-2906, 1993). To further
      investigate this problem, we have measured oxygen binding curves of single
      crystals of hemoglobin (in a different lattice) in which the iron in the alpha
      subunits has been replaced by the non-oxygen-binding nickel(II). The Hill n is
      0.90 +/- 0.06, and the p50 is slightly different for light polarized parallel to
      different crystal directions, indicating a very small difference in affinity
      between the two crystallographically inequivalent beta subunits. The average
      crystal p50 is 110 +/- 20 torr at 15 degrees C, close to the p50 of 80 torr
      observed in solution, but about threefold less than the p50 calculated by Rivetti
      et al. (Biochemistry 32:2888-2906, 1993) for the beta subunits of the
      unsubstituted tetramer. These results suggest that Rivetti et al., if anything,
      overestimated the alpha/beta inequivalence. They therefore did not underestimate
      the cooperativity within the T quaternary structure, when they concluded that it
      represents a small deviation from the perfectly noncooperative binding of an MWC
      allosteric model. Our conclusion of nearly perfect MWC behavior for binding to
      the T state of unmodified hemoglobin raises the question of the relevance of the
      large T-state cooperativity inferred for cyanide binding to partially oxidized
      hemoglobin (Ackers et al., Science 255:54-63, 1992).

PMID- 8865339
TI  - Quantifying biological specificity: the statistical mechanics of molecular
      recognition.
AB  - The Random Energy Model of statistical physics is applied to the problem of the
      specificity of recognition between two biological (macro)molecules forming a non
      covalent complex. In this model, the native mode of association is separated by
      an energy gap from a large body of non-native modes. Whereas the native mode is
      unique, the non-native modes form an energy spectrum which is approximated by a
      gaussian distribution. Specificity can then be estimated by writing the partition
      function and calculating the ratio r of non-native to native modes at
      thermodynamic equilibrium. We examine three situations: (i) recognition in the
      absence of a competitor; (ii) recognition in the presence of a competing ligand;
      (iii) recognition in a heterogeneous mixture. We derive the dependence of the
      ratio r on temperature and on the concentration of competing ligands, and we
      estimate the effect of a local perturbation such as can result from a point
      mutation. Cases (i) and (iii) are modeled by docking experiments in the computer.
      In case (iii), which is representative of a wide variety of biological
      situations, we show that increasing the heterogeneity of a mixture affects the
      specificity of recognition, even when the concentration of competing species is
      kept constant.

PMID- 8865340
TI  - Molecular mechanisms of pressure induced conformational changes in BPTI.
AB  - We have performed a 800 ps molecular dynamics simulation of bovine pancreatic
      trypsin inhibitor (BPTI) in water coupled to a pressure bath at 1, 10,000,
      15,000, and 20,000 bar. The simulation reproduces quite well the experimental
      behavior of the protein under high pressure. The protein keeps its globular form,
      but adopts a different conformation with a very small reduction in volume. Some
      residues in the hydrophobic core become exposed to water and a large part of the
      secondary structure of the protein, (60% of the sheet structure and 40% of the
      helical structure) is denatured between 10 and 15 kbar. This is in good agreement
      with experimental data (Goossens, K., et al. Eur. J. Biochem, 236:254-262, 1996)
      that show denaturation of BPTI between 8 and 14 kbar. A further increase of the
      pressure results in a freezing of the protein as deduced from the large decrease
      of the mobility of the residues. During the simulation, the normal structure of
      water changes from an ice Ih-like to an ice VI-like structure, while keeping the
      liquid state. The driving force of the high pressure induced conformational
      transition seems be the higher compressibility of the water compared with the
      protein. This produces a change in the solvent properties and leads to
      penetration of the solvent into the hydrophobic core.

PMID- 8865341
TI  - Evolution of beta-amylase: patterns of variation and conservation in subfamily
      sequences in relation to parsimony mechanisms.
AB  - Soybean and sweet potato beta-amylases are structured as alpha/beta barrels and
      the same kind of folding may account for all known beta-amylases. We provide a
      comprehensive analysis of both protein and DNA (coding region) sequences of beta
      amylases. The aim of the study is to contribute to the knowledge of the
      evolutionary molecular relationships among all known beta-amylases. Our approach
      combines the identification of the putative eightfold structural core formed by
      beta-strands with a complete multi-alignment analysis of all known sequences.
      Comparing putative beta-amylase (alpha/beta)8 cores from plants and
      microorganisms, two differentiated versions of residues at the packing sites, and
      a unique set of eight identical residues at the C-terminal catalytical site are
      observed, indicating early evolutionary divergence and absence of localized three
      dimensional evolution, respectively. A new analytical approach has been developed
      in order to work out conserved motifs for beta-amylases, mostly related with the
      enzyme activity. This approach appears useful as a new routine to find sets of
      motifs (each set being known as a fingerprint) in protein families. We
      demonstrate that the evolutionary mechanism for beta-amylases is a combination of
      parsimonious divergence at three distinguishable rates in relation to the
      functional signatures, the barrel scaffold, and alpha-helix-containing loops.

PMID- 8865342
TI  - The roles of residues Tyr150, Glu272, and His314 in class C beta-lactamases.
AB  - Serine beta-lactamases contribute widely to the beta-lactam resistance phenomena.
      Unfortunately, the intimate details of their catalytic mechanism remain elusive
      and subject to some controversy even though many "natural" and "artificial"
      mutants of these different enzymes have been isolated. This paper is essentially
      focused on class C beta-lactamases, which contain a Tyr (Tyr150) as the first
      residue of the second conserved element, in contrast to their class A
      counterparts, in which a Ser is found in the corresponding position. We have
      modified this Tyr residue by site-directed mutagenesis. On the basis of the three
      dimensional structure of the Enterobacter cloacae P99 enzyme, it seemed that
      residues Glu272 and His314 might also be important. They were similarly
      substituted. The modified enzymes were isolated and their catalytic properties
      determined. Our results indicated that His314 was not required for catalysis and
      that Glu272 did not play an important role in acylation but was involved to a
      small extent in the deacylation process. Conversely, Tyr150 was confirmed to be
      central for catalysis, at least with the best substrates. On the basis of a
      comparison of data obtained for several class C enzyme mutants and in agreement
      with recent structural data, we propose that the phenolate anion of Tyr150, in
      conjunction with the alkyl ammonium of Lys315, acts as the general base
      responsible for the activation of the active-site Ser64 during the acylation step
      and for the subsequent activation of a water molecule in the deacylation process.
      The evolution of the important superfamily of penicillin-recognizing enzymes is
      further discussed in the light of this proposed mechanism.

PMID- 8865343
TI  - Structure model of a complex between the factor for inversion stimulation (FIS)
      and DNA: modeling protein-DNA complexes with dyad symmetry and known protein
      structures.
AB  - A method is presented to predict overall conformations of protein-DNA complexes
      on the basis of the known three-dimensional structures of the proteins. The
      method is restricted to proteins with a common twofold symmetry axis, which show
      only minor conformational changes upon binding to DNA. The method uses a
      numerical finite difference solution of the linearized Poisson-Boltzmann equation
      and subsequent energy minimization cycles. Structural parameters-the rotation
      angle of the DNA relative to the protein around the common symmetry axis, the
      protein-DNA distance, and intermolecular hydrogen-bonding contacts-are presented
      for two test cases, DNA bound to CAP (catabolite gene activator protein) and to
      the Cro-repressor of bacteriophage 434. The DNA curvature in the starting model
      of the docking procedure was chosen as a smoothed approximation of the
      conformation found in the X-ray structures of these complexes. The method is
      further used to predict the unknown structure of the complex between the factor
      for inversion stimulation (FIS) and DNA, which is bent upon binding to FIS. In
      contrast to the test cases, the unknown curvature of the starting model is
      derived from a calibration of electrostatic precalculations for different
      proteins according to crystallographically observed DNA bending. The results of
      the modeling are in good accordance with the experimentally observed overall
      structure of protein-DNA complexes for the two test cases; for FIS, they
      correspond to several of the experimentally proposed protein-DNA contacts.

PMID- 8865344
TI  - In vivo association of protein fragments giving active AraC.
AB  - Frameshift mutations in a restricted portion of the arabinose operon regulatory
      gene araC from Escherichia coli give rise to active AraC protein, likely from the
      in vivo synthesis of two incomplete fragments that are active together. Synthesis
      of corresponding fragments, each separately inactive, from two plasmids within
      cells also resulted in complementation.

PMID- 8865345
TI  - Production and crystallization of a selenomethionyl variant of UmuD', an
      Escherichia coli SOS response protein.
AB  - Crystals of both native and mutant Escherichia coli UmuD' protein were obtained
      using the hanging drop method. Soaking the native crystals in solutions of heavy
      metal ions failed to produce good isomorphous derivatives, and selenomethionine
      substituted wild-type protein did not crystallize under conditions that gave
      native crystals. Site-directed mutagenesis was used to change the penultimate
      residue, a methionine amino acid, to either a valine or a threonine amino acid.
      Crystals were subsequently obtained from these mutant proteins with and without
      selenomethionine incorporation. Crystals of the native, the mutant, and the
      selenomethionine incorporated protein were all similar, crystallizing in the
      P4(1)2(1)2 space group.

PMID- 8865346
TI  - Crystallization of the purine salvage enzyme adenine phosphoribosyltransferase.
AB  - Adenine phosphoribosyltransferase from the protozoan parasite Leishmania donovani
      has been crystallized in the presence of the substrate Mg(2+)-alpha-D-5
      phosphoribosyl-1-pyrophosphate (PRPP) or the product adenosine-5-monophosphate,
      as well as in the absence of ligand. These crystals belong to the space group
      P6(1)22 or its enantiomorph P6(5)22, with unit cell dimensions of a = b = 64.0 A,
      c = 240.5 A, alpha = beta = 90 degrees, and gamma = 120 degrees. The crystals
      diffract to 1.9 A.

PMID- 8865347
TI  - Expression, purification, and crystallization of meso-diaminopimelate
      dehydrogenase from Corynebacterium glutamicum.
AB  - The gene encoding the meso-diaminopimelate dehydrogenase (DAPDH) from
      Corynebacterium glutamicum was over-expressed and purified to homogeneity.
      Crystals of the binary DAPDH-NADP+ complex were obtained from solutions of
      polyethylene glycol 8000, 100 mM sodium cacodylate, pH 6.5, and 150-300 mM
      Mg(OAc)2. The crystals diffract to 2.2 A, belong to the orthorhombic space group
      P2(1), and contain two molecules per asymmetric unit.

PMID- 8865349
TI  - Formal clinical characteristics of delusional beliefs.
AB  - We studied 13 formal clinical characteristics of delusions by means of observer
      rated ordinal scales in a sample of 74 psychiatric inpatients with mainly
      schizophrenic or schizophreniform disorders. The interrater reliability of the
      scales was found to be satisfactory. High levels of conviction about their truth
      and to a lower extent lack of dismissibility and lack of resistance against them
      were found to be the hallmarks of delusional beliefs. The lack of strong
      intercorrelations among the scales items supports the hypothesis that the concept
      of delusions represents various aspects of delusional experience which are
      relatively independent of one another.

PMID- 8865348
TI  - Expression and crystallization of the yeast Hsp82 chaperone, and preliminary X
      ray diffraction studies of the amino-terminal domain.
AB  - Expression of the Saccharomyces cerevisiae Hsp82 chaperone in a pep4-3- and hsc82
      deficient strain of S. cerevisiae yielded over 25% of the total cell protein as
      intact Hsp82. Similarly, the amino-terminal domain (residues 1-220) of Hsp82 was
      expressed to 18% of the total cell protein. Crystals of the intact Hsp82 were
      readily obtained. The crystals were very fragile, suggesting a high solvent
      content, and diffracted to approximately 8 A. Tetragonal bipyrimidal crystals of
      the amino-terminal domain of Hsp82 were readily obtained under a variety of
      different conditions. The crystals have primitive tetragonal space group (P422,
      P4(1)22, or its enantiomorph P4(3)22) with unit cell dimensions of a = 75.1 A and
      c = 111.3 A, contain 60% by volume solvent, and diffract to 2.5 A resoltuion.
      Addition of 25% glycerol to the mother liquor gave rise to large rod-shaped
      crystals. The crystals diffract to 2.8 A resolution, have an orthorhombic space
      group (P222(1), P2(1)2(1)2, or P2(1)2(1)2(1)) with cell dimensions of a = 45.2 A,
      b = 115.4 A, and c = 116.9 A, and a solvent content of 58% by volume.

PMID- 8865350
TI  - Delusional misidentification syndromes: a descriptive study.
AB  - Twenty-three patients with one or more delusional misidentification syndromes
      were studied. The majority of the subjects were females and the Capgras syndrome
      was the most common delusional misidentification syndrome in our sample. The
      Capgras syndrome cases were significant older than the Fregoli syndrome cases.
      Schizophrenia and schizo-affective psychosis were significantly associated with
      Fregoli syndrome. Discriminant function analysis was carried out on the sample
      and showed that age and symptoms of nuclear schizophrenia were the variables most
      predictive of the type of delusional misidentification. These findings are
      discussed in the light of current literature.

PMID- 8865351
TI  - Delusional misidentification: the illusion of Fregoli and a dog.
AB  - Misidentification syndromes have been regarded as psychiatric curious, but in
      recent years their importance both in terms of frequency, and because of their
      links with organic brain pathology and risk of violence has been increasingly
      realised. Most of the cases reported have been in conjunction with schizophrenia.
      We report a case of the illusion of Fregoli, the delusional misidentification of
      a familiar person in a stranger. The patient was manic and exhibited the delusion
      twice, once with regard to a man and the other concerning a dog.

PMID- 8865352
TI  - Eating and weight controlling behaviours of young ballet dancers.
AB  - Ballet dancers (n = 60) in full-time ballet training and school students (n =
      216) completed questionnaires relating to body weight and eating behaviour.
      Dancers were at lower body weight and had less body fat. Dancers considered they
      were more preoccupied with thoughts of eating and body weight, felt they had
      greater difficulty controlling their body weight, used and abused laxatives for
      weight control, and reported disordered eating more than school students. Two
      thirds of dancers and students were currently using at least one method of weight
      control, dancers favouring not eating between meals, and students exercise. Both
      groups reported binge eating and using multiple methods to control this
      behaviour. The pressure for dancers to be at below average weight affects their
      eating and weight controlling behaviours and their life-style. Young women such
      as dancers, gymnasts and some athletes are required to be at low body weight.
      These women maintain high levels of exercise. Whether ballet dancers are self
      selected as they are genetically slim, control their body weight with the higher
      levels of exercise or need to employ strategies to maintain their low body
      weight, has not been clarified. A significant proportion of ballet dancers have
      been reported to have symptoms of anorexia nervosa and to be described as 'weight
      preoccupied'. It has also been suggested that the incidence of disordered eating
      is greater in women who are under pressure to maintain low body weight. The aim
      of this study is to compare the eating and weight losing behaviour, attitudes and
      anthropomorphic characteristics of young women in full-time ballet training and
      those who are not.

PMID- 8865353
TI  - Characteristics of eating disorders among young ballet dancers.
AB  - The characteristics of anorexia nervosa and bulimia nervosa were studied in
      ballet dancers in full-time training and compared with other young women at
      school. Dancers had higher scores on the Eating Attitudes Test. Dancers were more
      likely to have an eating disorder when strict modified DSM-3-R criteria were
      applied. Currently 1 dancer (1.6%) and no student had anorexia nervosa, 1 dancer
      (1.6%) and 3 students (1.3%) had bulimia nervosa and 5 dancers (8.3%) and 9
      students (4.2%) had an unclassified eating disorder. Another dancer had been
      treated for anorexia nervosa in the past. One dancer was treated for bulimia
      nervosa and 6 for weight loss. Dancers were more likely to have been told to
      increase their body weight. Dancers were not more likely to be afraid of losing
      control of their weight and becoming obese if they attempted weight gain, to
      ignore the advice to gain weight or resist gaining weight. Regular self-induced
      vomiting was reported by 4% of women. Dancers are at risk for the development of
      eating disorders. Ballet dancers are under pressure to maintain low body weight.
      The low body weight and menstrual disturbance found among young dancers during
      training are two of the characteristics of anorexia nervosa Ballet dancers use
      behaviours aimed at weight control and weight loss. In dancers and professional
      groups under intense pressure to diet, low body weight and amenorrhoea are not
      sufficient criteria to diagnose anorexia nervosa. These behaviours can result in
      binge eating and multiple behaviours aimed at preventing binge eating. Whether
      the characteristics of bulimia among dancers are sufficient for a diagnosis of
      bulimia nervosa to be made is unknown. The aim of this paper is to study the
      characteristics of the eating disorders anorexia nervosa, bulimia nervosa and
      eating disorder not otherwise specified among young ballet dancers in full-time
      ballet training and to provide information about the risk of development of
      eating disorders among young women required to maintain below average body weight
      while continuing above average exercise.

PMID- 8865354
TI  - The importance of full summer remission as a criterion for the diagnosis of
      seasonal affective disorder.
AB  - From 1987 to 1994, seasonal affective disorder (SAD) has been diagnosed using the
      Rosenthal or DSM-III-R criteria. No major differences between them have been
      found, except that the DSM-III-R criteria were more stringent and difficult to
      implement. Little attention has been paid to differences in the criterion of the
      quality of improvement in summer. This study compared two groups of winter
      depressives characterized by complete or incomplete summer remission. Incomplete
      summer remission is associated with increased heterogeneity of the demographic
      and clinical profile of the disorder and a shift of this profile to that of
      classical depression. The data support clinical use of the DSM-IV criterion 'full
      remission' in the diagnosis of SAD.

PMID- 8865355
TI  - A case of Ganser's state presenting as a dementia syndrome.
AB  - We report an atypical case of Ganser's syndrome in a 54-year-old male patient.
      The following symptoms which include approximate answers perceptual disturbances
      and dissociative mechanisms were observed over 7 years, improved during
      hospitalization, but reappeared just before the patient's discharge. The
      extremely long presence and bizarre manifestation of symptoms, the course of the
      disorder and the patient's premorbid high intelligence level point to an unusual
      presentation of this case. Following the concept of hysteria and dissociation, we
      discuss its diagnosis within the scope of the DSM-III-R, DSM-IV and ICD-10
      classification of Dissociative Disorders. Problems in the differential diagnosis
      which result from an increasing awareness of Dissociative Disorders are outlined.

PMID- 8865356
TI  - On background factors of male genital self-mutilation.
AB  - Background factors of male genital self-mutilation have been suggested in a small
      series of cases. A review of 110 cases in the literature revealed that guilt
      feelings associated with sexual conflicts were the most important factors in the
      act of psychotic self-mutilation and also related to religious psychotic
      experiences that were often the direct motives for the act. Self-mutilators with
      sexual guilt feelings were likely to mutilate themselves more severely than those
      without. Even excluding transsexuals, disturbance of sexual identity was most
      participating in the act of nonpsychotic self-mutilators. In addition to these,
      previous history of self-injury took part in the act independently. Male genital
      self-mutilation is exceedingly rare in psychiatric practice even if it is not as
      uncommon as the paucity of published literature on the subject would suggest.
      According to Blacker et al., the earliest report in English of male genital self
      mutilation is Stroch's brief communication in 1901. Greilsheimer and Groves found
      53 cases in the English literature that had been reported till 1979. We present a
      case report with male genital self-mutilation and examine the background factors
      of this phenomenon from a review of the literature. We used the literature files
      'Medline' from 1979 to 1993 and the references of famous reports. In statistical
      analyses, we performed two-tailed t tests for continuous variables and chi 2
      tests with Yates correction for categorical variables.

PMID- 8865357
TI  - Compulsions developing into command hallucinations.
AB  - Intrusive, uncontrollable and bizarre thoughts occur in both obsessive-compulsive
      disorder (OCD) and psychosis. The origin of these mental phenomena and the
      relationship between them is unclear. A case is described in which long-standing
      compulsions and the associated resistance temporarily developed the
      characteristics of command hallucinations, in the absence of any other psychotic
      symptoms. The implications for psychopathological theories of hallucinations are
      discussed.

PMID- 8865358
TI  - Psychotic couvade: 2 case reports.
AB  - Couvade is a phenomenon, where the expectant father or another relative
      experiences somatic and/or psychiatric symptoms during a woman's pregnancy.
      Although epidemiological studies report a frequency of couvade symptoms between
      11 and 36% during all pregnancies, psychotic couvade cases are very rare with few
      case reports. The authors report 2 cases of psychotic couvade and give a
      psychodynamic interpretation of the cases. They emphasize the important role of
      ego defect and double identification in the development of the cases. Couvade is
      a phenomenon, where the expectant father or another relative experiences somatic
      and/or psychiatric symptoms during a woman's pregnancy. The term couvade was
      first coined by Tylor in 1865. Somatic symptoms can include indigestion or colic,
      gastritic symptoms, food cravings, nausea and vomiting, increased or decreased
      appetite, diarrhea, toothache, headache, itch, muscle tremors, nosebleed or other
      pains. Abdominal bloating and pseudocyesis have also been reported. Although the
      psychiatric symptoms most often observed are depression, anxiety, insomnia,
      irritability, tension and hypochondria there are some reports on psychotic
      couvade too. In our article we present 2 cases of psychotic couvade.

PMID- 8865359
TI  - Effects of extracellular cations and mutations in the pore region on the inward
      rectifier K+ channel IRK1.
AB  - It is known that the rectification property of the inward rectifier K+ channel,
      IRK1, is caused by a block of outward current by cytoplasmic Mg2+ and polyamines,
      and that the voltage dependence of rectification shifts according to the
      equilibrium potential of K+. Here it is shown that extracellular K+ (K+ o) but
      not intracellular K+ (K+ i) affects the activation kinetics of IRK1. A mutant in
      which the conserved positively charged residue arginine was replaced by a
      tyrosine (R148Y) exhibited slower activation and a negative shift of the
      conductance-voltage relationship. In addition, the conductance did not saturate
      at negative potentials as was observed for the wild type. When using T1+o instead
      of K+ o as permeant ion, the differences between the wild type and the mutant
      were qualitatively similar but less prominent. These results suggest that
      extracellular cations (e.g., K+ o or T1+ o) play a role in the activation of
      IRK1. Since the effects of K+ o or T1+ o were altered in the mutant, the site
      R148 presumably is involved in channel regulation by extracellular cations.

PMID- 8865360
TI  - Semiquantitative immunocytochemical analysis of GABAA receptor subunit expression
      in the rat neostriatum.
AB  - A semiquantitative immunogold technique was used to investigate the levels of
      expression of specific GABAA receptor subunits in different regions
      (dorsolateral, dorsomedial and ventromedial regions) of the rat striatum. The
      results indicate that the subunits studied can be classified into three groups on
      the basis of their labelling density in the striatum: alpha 1 and alpha 3
      (labelling density of less than 100 gold particles per 1000 microns2), gamma 2
      and delta (between 100 and 200 particles per 1000 microns2), and alpha 2 and beta
      2/3 (more than 300 particles per 1000 microns2). The alpha 1 and alpha 3 subunits
      are about 35% more abundant in the dorsal than in the ventral striatum, while the
      beta 2/3 and gamma 2 subunits are about 40% more abundant in the medial than in
      the lateral striatum. The alpha 2 and delta subunits did not show significant
      regional differences in abundance. The present data are consistent with the
      possibility that there are regional variations in the relative abundances of
      different GABAA receptor subtypes in the rat striatum.

PMID- 8865361
TI  - Modulation by dihydropyridines and protein kinases of the recombinant cardiac L
      type Ca channel with multiple unitary current amplitudes.
AB  - The cloned cardiac L-type Ca channel current expressed in baby hamster kidney
      (BHK) cells was characterized at the single channel level. After transfection of
      cDNA of the cardiac alpha 1 subunit along with skeletal beta, alpha 2/delta and
      gamma subunits to this cell line, recombinant Ca channels could be observed at
      high density over extended times. The properties of cloned Ca channels were
      almost identical with those of native cardiac L-type Ca channels, with respect to
      voltage dependence of activation, unitary conductance (25 pS with 100mM Ba2+ as
      the charge carrier and the modulation by a dihydropyridine (DHP) Ca channel
      agonist and an antagonist, or by 8Br-cAMP and phorbol esters. As in native
      cardiac Ca channels, changes in kinetic behavior during 8Br-cAMP application
      included increased number of channel openings and increased duration of open
      times. Phorbol esters also increased the number of openings with long duration.
      In 27 out of 37 patches in the presence of BayK8644, small amplitude openings of
      several levels were observed. These openings behaved similarly to the predominant
      25 pS openings during DHP and 8Br-cAMP application, with infrequent transitions
      to and from the predominant level. We conclude that BHK cells provide a useful
      expression system where the modulations and biophysical aspects of Ca channels
      can be studied at the single channel level.

PMID- 8865362
TI  - Effects of glycine on the mouse neuromuscular junction.
AB  - Glycine was applied at a range of different concentrations to test possible
      effects at the neuromuscular junction of the mouse. The presynaptic control of
      acetylcholine (ACh) release and the postsynaptic activation of the nicotinic
      receptor have been analysed by means of extracellular recording with an EPC7
      Patch Clamp amplifier. The results indicated that glycine did not modify in a
      significant manner the release of ACh and the postsynaptic cholinergic receptor
      function. Nevertheless, a significant increase in the rate of the conformational
      change of the receptor-ion channel complex seemed to be noteworthy. Glycine at 30
      and 300 microM increased in a dose dependent manner the decay time of the
      spontaneous miniature current. Concentrations of glycine exceeding 10mM
      completely blocked the activity of the end-plate in this preparation. In
      conclusion, we proved that glycine does not affect most of the parameters of
      neurotransmission in the mouse but, it increases the conformational change of the
      postsynaptic complex, perhaps inhibiting the acetylcholinesterase activity.

PMID- 8865363
TI  - GTP synthases. Proton pumping and phosphorylation in ligand-receptor-G alpha
      protein complexes.
AB  - A structural model for a ligand-receptor-Gs alpha-protein complex to function as
      a GTP synthase is presented. The mechanism which is dependent on the movement and
      rotation of the G alpha-protein alpha 2-helix is seen to involve the delivery of,
      at least, one proton to the phosphorylation site in the rotation of this helix.
      The cycle is driven by a ligand-mediated proton pump through the alpha-helices of
      the receptor, attachment of the conserved Tyr-Arg-Tyr receptor proton shuttle
      being made to an aspartate group on the Gs alpha-protein terminal sidechain,
      which is itself linked to the Asn-Gln interaction known to control movement and
      rotation of the alpha 2-helix between .GDP and .GTP structures. The energetics of
      proton transfer through the shuttle mechanism and delivery of a proton to the
      aspartate group are shown to be sufficient to rupture this controlling
      interaction and its associated backbone bond. The complex leads to full spatial
      and energetic definition of the receptor proton shuttle mechanism, while there is
      a striking association of further Tyrosine and Arginine residues in the vicinity
      of the Gs alpha-protein Asn-Gln interaction. Calculations at the HF 6-31G** level
      confirm that a critical balance between ion pair and neutral forms of Tyr-Arg
      interactions under multiply hydrogen bonded conditions in a hydrophobic
      environment controls proton transfer and recovery mechanisms. The intrinsic
      preference of the neutral Tyr-Arg form over the ion-pair is 14.0 kcal/mol.
      Activation of the Tyrosine oxygen atom in the neutral form by single-NH or -OH
      groups reduces this difference by some 6.4-8.6 kcal/mol but the dominance of the
      neutral form is maintained. The expected slight overestimates are consistent with
      the maximum activation enthalpy of 11.0-12.0 kcal/ mol required to initiate
      proton transfer through the shuttle. The extended form of the shuttle with the
      Arginine acting competitively between the two Tyrosine residues allows
      interpretation of observed enthalpic differences in ligand binding with and
      without the presence of GTP. The uniqueness of Gs proteins among the G alpha
      proteins is seen as their inability to transfer a proton directly through the
      alpha 2-helix switch Asn-Gln residues. A possible proton pathway to the mid-point
      of the Gs alpha-protein alpha 2 helix is outlined.

PMID- 8865364
TI  - Pharmacological and biochemical characterization of the mouse 5HT5A serotonin
      receptor heterologously produced in the yeast Saccharomyces cerevisiae.
AB  - The cDNA for the mouse 5HT5A receptor has been functionally expressed in the
      unicellular yeast Saccharomyces cerevisiae. The NH2-terminal end of the receptor
      gene was fused to the Bacillus macerans (1-3, 1-4)-beta-glucanase signal sequence
      to ensure proper membrane insertion and to the c-myc epitope to permit
      immunological detection of the heterologously expressed protein. In the resulting
      episomal yeast expression plasmid pCNNmm5HT5A the modified 5HT5A gene is under
      the transcriptional control of the endopeptidase B gene promoter (PRB1). After
      transformation of the vector into the protease deficient S. cerevisiae strain cI3
      ABYS-86, recombinant clones were examined for the presence of functional receptor
      by radioligand binding using [3H]LSD. Whole cells as well as crude membrane
      preparations of recombinant clones showed saturable binding of the receptor with
      a KD of approximately 2.2 nM. The pharmacological properties for the heterologous
      expressed receptor, estimated by ligand-displacement studies using certain
      serotonin agonists and antagonists, were comparable to those reported for the
      receptor expressed in mammalian systems. Western blot analysis of membranes
      prepared from a recombinant clone using the monoclonal antibody 9E10, directed
      against the c-myc epitope of the modified receptor, revealed an apparent
      molecular mass of about 43 kDa for the receptor expressed in S. cerevisiae.
      Glycosylation of the receptor was analysed by EndoH digestion. A heat shock of
      recombinant yeast significantly increased the number of specific binding sites
      per cell and also improved the affinity of the receptor. Immunogold electron
      microscopy was used to study the localization of the heterologously expressed
      protein within the yeast cells.

PMID- 8865365
TI  - Acceleration of corneal wound healing in diabetic rats by the antioxidant trolox.
AB  - Several corneal complications have been reported in patients with long standing
      diabetes, but their exact pathogenesis is not well understood. It has been
      observed that the rate of epithelial wound healing in diabetic rats is delayed
      compared to those in normal animals. Here we present the effect of the free
      radial scavenger, Trolox, a water soluble vitamin E analogue, on epithelial wound
      healing in diabetic rat cornea. Three groups of rats were included: 1) normal, 2)
      diabetic, 3) diabetic + Trolox. After 3 months, rats were sacrificed and corneas
      removed. Standard 3 mm diameter corneal epithelial defects were made and residual
      epithelial defects were measured after 18 hours at 37 degrees C in a sterile cell
      culture incubator. Wound healing data measured in mm2 was used for statistical
      analysis. There were significantly larger (p < 0.05) epithelial defects in
      diabetic corneas as compared to control. Treatment with Trolox antioxidant in
      diabetic rats produced a significantly smaller (p < 0.05) epithelial defect than
      that of untreated diabetic rats. These studies suggest the involvement of free
      radicals in the delay of corneal epithelial wound healing in diabetes.

PMID- 8865366
TI  - Expression and distribution of glucose-6-phosphatase catalytic subunit messenger
      RNA and its changes in the diabetic state.
AB  - Glucose-6-phosphatase (G6Pase) plays a major role in gluconeogenic pathway. To
      analyze its regulation, we have cloned a full-length cDNA for G6Pase catalytic
      subunit from the rat liver. In the cloned cDNA, a 492 base insertion, respective
      to the previously reported sequence, was found in the 3'-noncoding region. In
      both ends of this insertion, 5'- and 3' 2' splice site motifs were identified.
      However, spliced mRNA was hardly observed in the rat RNA. Abundant expression was
      observed in the liver and the kidney by Northern analysis. Expression was also
      observed in the spleen, adrenal gland and small intestines. Reverse-transcription
      (RT) polymerase chain reaction (PCR) analysis revealed that G6Pase mRNA was also
      expressed in a variety of tissues including pancreatic islets. Its expression was
      increased in the ketotic diabetic mice livers and was corrected by insulin
      treatment. However, no appreciable changes were observed in kidneys. Broad tissue
      distribution in expression and the tissue specificity in regulation were thus
      considered to be the important features of G6Pase gene.

PMID- 8865367
TI  - Restriction fragment length polymorphism of the human apo B and apo AII gene
      regions among type II diabetics.
AB  - Levels of plasma low density lipoproteins (LDL) are positively, and high density
      lipoproteins (HDL) are negatively correlated with an increased risk for
      atherosclerosis. The frequencies of restriction fragment length polymorphism
      (RFLP) of the genes for apoB, a major LDL apolipoprotein, and apoAII, a major HDL
      apolipoprotein, were studied in 45 Tunisian diabetics and an equal number of sex
      and age matched controls. Southern blot analysis of an EcoR1 apoB polymorphism
      and an Msp1 apo AII polymorphism indicates that there was no statistically
      significant difference in the incidence of different genotypes or alleles among
      diabetics compared to controls.

PMID- 8865368
TI  - Role of protein phosphatase in malignant osteogenic and soft tissue tumors.
AB  - The expression of the three catalytic subunits of protein phosphatase (PP) type 1
      and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in osteogenic tumors and
      soft tissue tumors by immunohistochemical analysis. The percentage of cells
      stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma
      1, was significantly higher in malignant osteogenic tumors (chondrosarcoma,
      osteosarcoma, and Ewing's sarcoma) and in malignant soft tissue tumors
      (liposarcoma and malignant fibrous histiocytoma [M.F.H.]) than in benign tumors
      (osteochondroma, osteoblastoma, ossifying fibroma, enchondroma and lipoma).
      Furthermore, the malignant tumor lesions showed a markedly high number of cells
      in the S-phase fraction of the cell cycle, as compared to benign tumors. These
      results suggest that PP1 gamma 1 is involved in the accelerated growth of
      malignant tumor cells.

PMID- 8865369
TI  - Trimethadione N-demethylation by rat liver CYP2E1 in vitro.
AB  - Trimethadione (TMO) is a model drug utilized for estimation of hepatic metabolism
      in clinical studies, and it was reported that TMO N-demethylase activity was
      inhibited by CYP2E1 inhibitors and substrates in rat in vivo. This study was
      performed to investigate the involvement of the CYP2E1 subfamily on TMO N
      demethylation in vitro and to clarify these inhibitory mechanisms. The effects of
      acetone (AC), imidazole (IM) and N-nitrosodimethylamine (NDA) on TMO N
      demethylation were studied in vitro. Rat hepatic microsomal fractions were
      employed as the enzyme source of TMO N-demethylase and the activity was
      determined by the production of dimethadione (DMO). DMO was analyzed by a GC/FTD
      equipped with a narrow-bore capillary column. TMO N-demethylation was biphasic by
      the graphic analysis of Eadie-Hofstee plots; this suggests the involvement of at
      least two enzymes in TMO metabolism in the rat. The kinetic parameters for the
      formation of DMO were analyzed graphically using double-reciprocal plots. The
      apparent K(m1), K(m2) and Vmax1, Vmax2 values for DMO formation were 4, 20 mM and
      182, 595 pmol/mg protein/min, respectively. AC and IM inhibited TMO N-demethylase
      activity competetively. However, mixed inhibition kinetics was observed by NDA.
      Furthermore, TMO N-demethylase activity was inhibited by antiserum to CYP2E1 by
      62% and CYP3A2 by 46%. These results indicate that the CYP2E1 subfamily is the
      major enzyme involved in TMO N-demethylation in rat in vitro although the CYP3A2
      is also involved in this transformation.

PMID- 8865370
TI  - Lipid peroxidation inhibited by monoamines.
AB  - We investigated the inhibition of lipid peroxidation by monoamines. We found that
      monoamines, including dopa, dopamine, adrenaline and serotonin, strongly
      inhibited lipid peroxidation induced by 2,2'-azobis-(2-amidinopropane)
      dihydrochroride (AAPH). In contrast, lipid peroxidation induced by 2,2'-azobis
      (2,4-dimethylvaleronitrile) was not effectively inhibited by the monoamines.
      Degradation of R-phycoerythrin induced by AAPH was strongly prevented by these
      monoamines, suggesting that monoamines scavenge peroxyl radicals in the buffer
      and on the surface of membrane lipid layers. Methoxy derivatives of
      dihydroxyphenylacetic acid and 5-methoxytryptophan produced little inhibition of
      lipid peroxidation induced by AAPH, suggesting that hydroxy groups of monoamines
      donate protons to peroxyl radicals to prevent lipid peroxidation. However, the
      monoamines did not sharply inhibit lipid peroxidation induced by ascorbate-ADP
      Fe3+ and t-butylhydroperoxide-Fe2+. Lipid peroxidation predominantly proceeding
      by peroxyl radicals in these reaction systems seems unlikely.

PMID- 8865371
TI  - Effect of triiodothyronine on nitric oxide production in mesangial cells and
      renal tubular epithelial cells.
AB  - Nitric oxide (NO) is a signalling molecule that is produced by mesangial cells
      and renal tubular epithelial (RTE) cells. It plays a role in the regulation of
      glomerular and tubular function. In renal cells, NO is synthesized by the
      inducible isoform of the enzyme nitric oxide synthase (NOS). Thyroid hormone
      modulates the activity of neuronal NOS; therefore, we examined whether
      triiodothyronine (T3) stimulated the activity of inducible iNOS in mesangial
      cells, LLC-PK1 cells (analogue of the proximal tubule) and MDCK cells (analogue
      of the distal tubule). T3 (concentration range: 10(-10)-10(-7) M) had no effect
      on NO synthesis or iNOS protein expression by the three renal cell types. In
      addition, T3 did not modulate NO production in RAW 264.7 cells, a murine
      macrophage cell line, confirming that the hormone had no effect on iNOS activity.
      We conclude that, unlike its effect on neuronal NOS, T3 does not regulate iNOS
      activity in mesangial cells, RTE cells, or macrophages, and that the effects of
      T3 on renal cell growth and function are not mediated by inducible increases in
      NO synthesis.

PMID- 8865372
TI  - Oxidation of Tris and formaldehyde to CO2 by neutrophil oxidants.
AB  - The buffer substance Tris is oxidized to formaldehyde by two microbicidal
      neutrophil oxidants, the hydroxyl radical and sodium hypochlorite. By the intact
      neutrophil, Tris is converted to CO2 in a process which is enhanced by
      stimulation with zymosan indicating that CO2 formation reflects neutrophil
      function. CO2 formation is more extensive at pH 6.0 than at pH 7.5 suggesting
      higher microbicidal activity at the low pH of inflamed tissue. In addition to
      Tris, its oxidation product formaldehyde is also oxidized to CO2 by hydroxyl
      radicals, and the formation of CO2 from formaldehyde by intact neutrophils
      exhibits the same features as CO2 formation from Tris. It is suggested that CO2
      formation from Tris or from formaldehyde may be suitable to test for the
      formation of microbicidal oxidants by neutrophils.

PMID- 8865373
TI  - Interaction between propofol and sulfisoxazole in mice an in vivo and in vitro
      study.
AB  - The effect of sulfisoxazole on the propofol response has been investigated in an
      animal model. Doses of propofol (0, 50, 75 and 100 mg/Kg intraperitoneal route)
      were administered to control (n = 36) and sulfisoxazole pretreated mice (n = 36).
      The impairment of righting reflex and struggle response were evaluated before and
      5, 10, 15, 20, 30, 40, 50 and 60 minutes after propofol administration. Ten
      minutes after administration of the different doses of propofol, total plasma
      concentration was measured in both groups by high performance liquid
      chromatography Protein binding displacement was evaluated in vitro by the
      ultrafiltration technique. Pretreatment with sulfisoxazole produced an important
      enhancement in the effect of propofol in both tests. This change was reflected in
      a significant increase in the area under the time-effect curve (p < 0.001) and in
      a shift of the log dose-effect relationship to the left. Sulfisoxazole itself did
      not produce any effect on either test. ED50 for the righting reflex was
      significantly reduced from 114 mg/kg to 64 mg/kg in sulfisoxazole pretreated
      groups and it fell from 87 mg/kg to 43 mg/kg for the struggle response test. No
      changes in the total plasma concentration and protein binding were observed. On
      the basis of these results, it was concluded that a clinical interaction could be
      expected but this cannot be explained by an alteration in the protein binding.

PMID- 8865374
TI  - Gold replacement of cadmium, zinc-binding metallothionein.
AB  - We analyzed the gold-binding capacity and property of metallothionein by
      replacement of the Cd, Zn-binding metallothionein with Au. Unlike native Cd,Zn
      metallothionein, the ultraviolet absorption spectrum of Au-metallothionein was
      very similar to that of apo-metallothionein. The maximum binding ratios of Au and
      Cd per metallothionein replaced with Au were 9 and 2, respectively. Since the
      maximum binding ratio of Au per metallothionein with Au (III) was estimated to be
      12 g atoms of Au per metallothionein, it was inferred that Au was bound to
      metallothionein as Au (I). The results indicate that Au (III) exhibits stronger
      binding affinity than Zn and Cd to metallothionein.

PMID- 8865375
TI  - Effect of water deprivation for 48 hours on the pharmacokinetics and
      pharmacodynamics of azosemide in rats.
AB  - The effect of temporary water deprivation for 48 h on the pharmacokinetics and
      pharmacodynamics of azosemide was examined after intravenous (i.v., 10 mg/kg) and
      oral (20 mg/kg) administration of azosemide to the control and the water-deprived
      rats. After i.v. administration of azosemide, the area under the plasma
      concentration-time curve from time 0 to time infinity and the unbound fraction of
      azosemide to plasma proteins increased by 36 and 40%, respectively, and total
      body, renal (CLR), and nonrenal clearances, apparent volume of distribution at
      steady state, and total amount of azosemide excreted in urine (AeAZ0) decreased
      by 30, 44, 20, 25, and 33%, respectively, in the water-deprived rats (p < 0.05 vs
      controls). After oral administration of azosemide, the values of AeAZ0 (591 vs
      318 micrograms) and CLR (2.22 vs 0.875 mL/min/kg) decreased significantly in the
      water-deprived rats. The 12-h urine output per g kidney was also reduced
      significantly in the water-deprived rats after both i.v. (70.3 vs 24.6 mL) and
      oral (70.7 and 20.7 mL) administration of azosemide. This could be due to the
      significantly reduced amount of azosemide excreted in 12 h urine, significantly
      higher plasma osmolarity, and increased blood vasopressin concentration in the
      water-deprived rats. The 12-h urinary excretion of sodium, potassium, and
      chloride per g kidney was also reduced significantly in the water-deprived rats
      after both i.v. and oral administration. The diuretic efficiency decreased
      significantly in the water-deprived rats after both i.v. and oral administration.
      The 12-h urine output per g kidney of i.v. and oral administration of azosemide
      in the control rats were similar (70.3 +/- 17.3 vs 70.7 +/- 13.8 mL), although
      the AeAZ0 after oral administration was significantly smaller than that after
      i.v. administration (473 +/- 98.5 vs 285 +/- 76.3 micrograms), and similar
      results were also obtained from the water-deprived rats. This could be
      rationalized by the concept of a single maximally efficient excretion rate of the
      drug in the pharmacodynamic model (sigmoid Emax), as shown for furosemide.

PMID- 8865376
TI  - cAMP-dependent modulation of L-type calcium currents in mouse diaphragmatic
      cells.
AB  - The regulation of calcium channels by cAMP-dependent phosphorylation was
      investigated in the diaphragm muscle. Experiments were performed on dissociated
      costal diaphragmatic cells from 16- to 17-day-old fetal mice. The ionic current
      through calcium channels was measured using the whole cell clamp technique with
      barium as the charge carrier. A depolarizing pulse delivered from a holding
      potential of -80 mV elicited a low-threshold dihydropyridine (DHP)-insensitive T
      type current and a high-threshold DHP-sensitive L-type current. Agents that
      either increase intracellular cAMP levels (forskolin, 10(-4) M, and
      dibutyryladenosine 3'-5' cyclic monophosphate, 10(-4) M) or inhibit cAMP
      degradation (theophylline, 10(-4) M) produced relative increases in L-type
      current amplitude of 24.4 +/- 13.8%, 13.4 +/- 4.6%, and 15.9 +/- 2.8% (p < 0.05),
      respectively. Current intensity increased after application of the beta
      adrenergic agonist isoproterenol (10(-5) M, 16.5 +/- 3.6%, P < 0.005). None of
      these agents affected the T-type current. These results suggest that L-type
      calcium channel activities of the diaphragm muscle are regulated by cAMP
      dependent phosphorylation.

PMID- 8865377
TI  - Phrenic response to hypercapnia in the unanesthetized, decerbrate, newborn rat.
AB  - We developed a decerebrate, vagotomized, newborn rat preparation to investigate
      brainstem respiratory control mechanisms without the influence of anesthesia,
      supra-pontine structures, or vagally mediated feedback mechanisms. We measured
      the changes in phrenic nerve electrical activity in response to breathing 3% and
      5% CO2 in unanesthetized, vagotomized, decerebrate newborn rats from 0 to 10 days
      of age and compared them with the changes in anesthetized, vagotomized, newborn
      rats and adult, vagotomized, decerebrate or anesthetized, animals. Phrenic nerve
      activity was irregular in the young newborn rats and became more regular between
      7 and 10 days of age. T1 and T1/Ttot increased with age but increasing age had no
      influence on the response to CO2. The response to CO2 was dominated by increases
      in phrenic amplitude, minute activity, and inspiratory slope with no change in
      timing variables. These responses are similar to those that have been reported
      previously in vagally intact animals, suggesting that vagal feedback contributes
      little to the response to hypercapnia in the newborn rat. In summary, decerebrate
      newborn rats consistently respond to hypercapnia by increasing inspiratory drive
      similar to conscious animals.

PMID- 8865378
TI  - The effect of chest wall transcutaneous electrical nerve stimulation on dyspnoea.
AB  - We studied the effects of transcutaneous electrical nerve stimulation (TENS) over
      the chest wall on breathlessness in normal subjects during exercise. Eleven male
      subjects performed a progressive incremental exercise test to break point on four
      consecutive days. TENS (continuous form, frequency 100 Hz, pulse width 200
      microseconds) was applied during three of these tests-over the second intercostal
      spaces during inspiration ('in phase' with the underlying inspiratory muscle
      contraction) or expiration ('out of phase' with contraction) or over the deltoid
      muscles during inspiration (control), and not on the fourth occasion in random
      order. Breathlessness (Borg scale), heart rate, respiratory frequency, tidal
      volume, minute ventilation and minute oxygen uptake were measured. No significant
      differences were found for any of the measured variables between the four study
      days. We conclude that TENS under these circumstances has no effect on the
      sensation of breathlessness or on the measured physiological variables in normal
      subjects during exercise.

PMID- 8865379
TI  - Respiratory muscle coordination in acute spinal dogs.
AB  - Our objectives were (1) to test whether respiratory muscles of spinal dogs can
      generate the alternating pattern of activation seen in intact animals and (2) to
      characterize the responsiveness of spinal rhythms to mechanical ventilation. We
      recorded the electromyographic activities of inspiratory muscles (diaphragm and
      parasternal intercostals) and expiratory muscles (triangularis sterni and
      transversus abdominis) in ten anesthetized dogs before and after transection of
      the cervical cord at levels C1-C2 (n = 2), C2-C3 (n = 6), and C8 (n = 2). In 9/10
      dogs, we observed short lasting (3-4 min) rhythmic ventilatory muscle activity
      for up to 3 h after transection. Inspiratory and expiratory muscles contracted
      simultaneously, suggesting an absence of mechanism(s) responsible for reciprocal
      muscle activation on a spinal level. Five of ten dogs showed tonic rib cage
      activity during apnea that was phasically modulated during mechanical
      ventilation. From the absence of alternating inspiratory and expiratory muscle
      activity in acute spinalized dogs, we conclude that dogs do not have a spinal
      pattern generator for respiration.

PMID- 8865380
TI  - Severe endurance training fails to change myosin heavy-chain distribution of
      diaphragm.
AB  - Histochemical analysis by Green et al. (1989) revealed that severe endurance
      training caused a transformation from type IIA to type IIB fibres in the costal
      diaphragm region of the rat. With the use of the electrophoretic method, in the
      current study, it was re-examined whether such a change was brought about in this
      respiration muscle. The animals were capable of running for 240 min/day at 40
      m/min during the final phase of a 16-week training program. Four heavy-chain (HC)
      isoforms were separated by a single percentage polyacrylamide gel electrophoresis
      of extracts from muscles. Densitometric analysis of these HC isoforms revealed
      that exercise training failed to change the relative distribution of any HC
      isoforms in the diaphragm.

PMID- 8865381
TI  - Blood viscosity in chronically hypoxic rats: an effect independent of packed cell
      volume.
AB  - We compared apparent blood viscosity, measured with a cone-plate viscometer, in
      normoxic and chronically hypoxic rats. All comparisons were made at equal packed
      cell volume (PCV) and shear rate conditions. Apparent viscosity of whole blood
      from the hypoxic rats was significantly lower than that from normoxic littermates
      and was similar to that of young rats. Apparent viscosity of red cells from
      hypoxic rats suspended in phosphate buffered saline remained lower than that from
      the normoxic rats. When blood cells from the hypoxic rats were suspended in
      plasma from normoxic rats, apparent viscosity was lower than when blood cells
      from normoxic animals were suspended in plasma from hypoxic rats. The lower
      viscosity of the blood from hypoxic rats appears to be associated with
      characteristics present in newly generated red cells. The reduced apparent
      viscosity of blood in hypoxic rats may partially compensate for the increase in
      PCV, at least during the early stages of hypoxia.

PMID- 8865382
TI  - Laryngeal CO2 receptors: influence of systemic PCO2 and carbonic anhydrase
      inhibition.
AB  - Responses of laryngeal receptors selected for their responsiveness to 10%
      intralaryngeal CO2 were recorded in single fibers of the superior laryngeal nerve
      at a wide range of systemic PCO2 values and before and after carbonic anhydrase
      inhibition in anesthetized, paralyzed, ventilated cats. Carbonic anhydrase was
      inhibited, locally, by perfusing the upper airways with either acetazolamide or
      methazolamide (10(-2) M) or systemically, by injecting acetazolamide
      intravenously (5, 10, or 25 mg/kg). Of the 58 receptors studied, 55 decreased
      their discharge rate in response to 10% intralaryngeal CO2, whereas 3 increased
      their discharge in response to intralaryngeal CO2. The majority of these
      receptors also increased their discharge rate in response to positive laryngeal
      pressure. Neither increased nor decreased systemic PCO2 influenced the receptors'
      baseline discharge rate or their response to intralaryngeal CO2. Topical
      inhibition of carbonic anhydrase did not consistently alter the maximal
      inhibitory response to CO2 or the initial rate of change of receptor activity. On
      the other hand, intravenous injections of acetazolamide caused, within 30 sec, a
      consistent attenuation of both the initial rate of change and the maximal
      inhibitory response to intralaryngeal CO2. These results indicate that the sub
      set of laryngeal receptors that are sensitive to intralaryngeal CO2 are not
      responsive to changes in systemic PCO2. The carbonic anhydrase inhibition
      experiments show that this enzyme plays an important role in the ability of these
      receptors to detect both transient and steady-state changes in intralaryngeal
      CO2.

PMID- 8865383
TI  - Respiratory mechanics in the open chest: effects of parietal pleurae.
AB  - To understand how the parietal pleurae affect the mechanical behavior of the
      human respiratory system after the chest wall is opened by median sternotomy, we
      studied 18 anesthetized/paralyzed patients immediately before coronary artery
      bypass grafting surgery. Elastances and resistances of the total respiratory
      system (ETr, Rrs) were calculated from measurements of airway pressure and flow
      during mechanical ventilation in the frequency and tidal volume ranges of normal
      breathing. Elastances and resistances of the lungs (EL, RL), chest wall (Ecw,
      Rcw) were also estimated from measurements of esophageal pressure. Data were
      collected in the closed chest, after median sternotomy with the parietal pleurae
      intact and after the left parietal pleura was opened for internal mammary artery
      harvest. After sternotomy with pleurae intact (n = 14), Ers did not change but
      Rrs decreased (p < 0.05). Ecw (including the contribution of the pleurae) was
      higher than in the closed chest (p < 0.05) while EL and RL were lower (p < 0.05);
      Rcw did not change. Opening the left pleura (n = 10) decreased Ers (p < 0.05),
      but Rrs did not change. We conclude that the chest wall/pleurae compartment
      offers significant impedance to lung expansion after sternotomy and rib
      retraction, unless one pleura is opened.

PMID- 8865384
TI  - CO2 response for the brain stem artery blood flow velocity in man.
AB  - We examined changes in the blood flow velocity of brain stem artery (BSA) and
      middle cerebral artery (MCA) in response to hypercapnic, normocapnic and
      hypocapnic hyperventilation in seven awake subjects with a transcranial Doppler
      to determine if there are differences in blood flow control in regional brain
      perfused by these respective arteries, and to separate the effects of CO2 and
      ventilation itself on blood flow velocity during CO2 loading. During hypercapnic
      hyperventilation, BSA flow velocity increased linearly with an increase in end
      tidal partial pressure of CO2 (PETCO2). During hypocapnic hyperventilation, BSA
      flow velocity decreased linearly with decrease in PETCO2, but did not change
      during normocapnic hyperventilation. The mean CO2 reactivity of BSA was
      2.8%/mmHg. The responses of MCA to these hyperventilations and CO2 reactivity
      were similar to those of BSA. These findings suggest that CO2 rather than
      ventilation per se is the important stimulus to changes in brain blood flow
      velocity and that the CO2 responses of brain arteries are not affected by
      differences in vascular beds.

PMID- 8865386
TI  - Epiretinal macular membranes in eyes with attached posterior cortical vitreous.
AB  - BACKGROUND: The authors define the clinical and anatomic characteristics of
      patients who had epiretinal membrane formation and traction over the macula in
      the absence of vitreous detachment from the retina. METHODS: Patients were
      treated and followed by one surgeon (JCF). All patients had epiretinal membrane
      formation over the macula without vitreous detachment. The clinical and surgical
      findings of these patients were compared along with histopathologic examination
      of the removed epiretinal membranes and posterior cortical vitreous. RESULTS:
      Fourteen patients were identified over a 9.75-year period. All patients had a
      thin and transparent-or at most minimally translucent-membrane overlying the
      posterior pole causing traction. The membrane appeared continuous with the
      posterior hyaloid face. At vitrectomy, no vitreous detachment was found in any
      eye. Transmission electron microscopy of all three specimens tested found
      collagen of less than 16 nanometers in diameter, consistent with native vitreous
      collagen. After surgery, visual acuity improved in 13 of 14 eyes, was 20/50 or
      better in 12 eyes, and was 20/25 or better in 7 eyes. CONCLUSION: Epiretinal
      membrane formation can occur in eyes without vitreous detachment probably because
      of cellular growth along the posterior hyaloid face. Such eyes respond
      particularly well to surgery.

PMID- 8865385
TI  - Inositol phosphate turnover in human airways: effect of arachidonic acid
      metabolism.
AB  - The aim of this study was to examine the role of the phospholipase A2-arachidonic
      acid (PLA2-AA) pathway in response to histamine and the possible effect of AA
      metabolites on the generation of inositol-phosphates (IPs) in airway smooth
      muscle cells (SMC). Radiolabelled IPs-were analyzed by high-performance liquid
      chromatography (HPLC). Indomethacin, a cyclooxygenase inhibitor, potentiated the
      IP production evoked by a 5-sec application of histamine, while it decreased the
      effect of a 5-min incubation with the agonist, suggesting a time-dependent
      modulation of phospholipase C (PLC) activity by prostaglandins (PGs). Exogenous
      AA elicited the generation of IPs; this effect was suppressed by cyclooxygenase
      inhibition. Therefore, several steps in the AA metabolic pathways appear to
      modulate the production of IPs in human airway SMC.

PMID- 8865387
TI  - Use of perflubron as a new temporary vitreous substitute and manipulation agent
      for vitreoretinal surgery. Wills Eye Hospital Perflubron Study Group.
AB  - PURPOSE: The authors determine the intraocular tolerance of a new widely used
      liquid perfluorocarbon, perfluoroctylbromide (perflubron). METHODS: Pars plana
      vitrectomy was performed on 54 eyes of 54 patients with vitreoretinal disorders
      at three centers. Diagnoses included giant retinal tears, proliferative
      vitreoretinopathy, and dislocated intraocular and crystalline lenses. At the
      conclusion of the vitrectomy, perflubron was removed. RESULTS: Perflubron was
      efficacious for vitreoretinal manipulation. Of the 45 eyes with retinal
      detachment, 23 (51.1%) of the retinas were reattached after a single surgery;
      redetachment occurred in 22 (48.9%) after the initial procedure, and further
      surgery was necessary to reattach the retina. Final retinal reattachment was
      achieved in 40 (88.9%) eyes. Mean visual acuity improvement was six lines (P <
      0.0019). Visualization of the water/perfluorocarbon interface was good. There was
      no evidence of adverse effects from perflubron on the retina, lens, or anterior
      segment. CONCLUSION: Findings indicate that perflubron is safe for temporary
      intraoperative use intravitreally. The absence of adverse effects is consistent
      with the properties of perflubron that our group has studied in the eyes of
      animals and in other uses in human patients.

PMID- 8865388
TI  - Rubeosis of the iris in proliferative vitreoretinopathy.
AB  - PURPOSE: The authors report the findings and clinical course of rubeosis in
      patients with essentially reattached retinas after vitrectomy and silicone oil
      for proliferative vitreoretinopathy (PVR). METHODS: From 1989 on, the authors
      prospectively noted all patients with rubeosis and with attached retina posterior
      to the buckle after vitrectomy and silicone oil for PVR as a complication of
      rhegmatogenous retinal detachment. RESULTS: Thirty-eight patients (38 eyes) were
      studied. Mean follow-up after the appearance of rubeosis was 27 months (range, 6
      66 months) in all patients, peripheral residual retinal detachment coexisted with
      rubeosis. Hypotony occurred in six patients. Cyclocryocoagulation for neovascular
      glaucoma had been performed in four patients. The peripheral detached retina was
      removed in 16 patients, resulting in total disappearance of rubeosis in 7
      patients and regression in 4 more patients. In patients with visible, nonradially
      oriented iris vessels, the authors found vessels in the anterior chamber angle
      crossing the trabecular meshwork. The frequently present anterior synechiae in
      association with vessels never totalled more than three clock hours (except in
      the four patients who underwent cyclocryocoagulation). CONCLUSIONS: Detached
      retina peripheral to dense photocoagulation scars was present in all of these
      patients. Removal of this peripheral detached retina was statistically
      significantly associated with disappearance of rubeosis, which suggests that the
      peripheral detachment was a causative factor. Extensive anterior synechiae are
      not formed frequently in this condition. This may explain the infrequent (11%)
      occurrence of neovascular glaucoma. However, hypotony is more frequent.

PMID- 8865389
TI  - Scanning laser ophthalmoscope macular perimetry in the evaluation of submacular
      surgery.
AB  - PURPOSE: Submacular surgery for choroidal neovascularization (CNV) is under
      investigation in the treatment of age-related macular degeneration (AMD) and the
      presumed ocular histoplasmosis syndrome. Four case studies are presented to
      demonstrate scanning laser ophthalmoscope (SLO) testing in the pre- and
      postsurgical evaluation of visual function in patients with subfoveal CNV
      secondary to AMD, presumed ocular histoplasmosis syndrome, and submacular
      hemorrhage secondary to AMD. METHODS: Patients underwent a visual assessment pre-
      and 6 months postoperatively, consisting of low vision visual acuity measurement,
      SLO macular perimetry of dense and relative scotomas, and analysis of the
      preferred retinal locus for fixation (PRL) location and ability. RESULTS: Visual
      acuity, dense and relative scotoma size and location, and PRL location were
      compared; and relationships between anatomic and functional changes were
      observed. Decreases in scotoma size and improvement in PRL location and ability
      usually corresponded with improved visual acuity. Preoperative scotoma and PRL
      location guided retinotomy site selection. CONCLUSION: Scanning laser
      ophthalmoscope macular perimetry and PRL testing may be useful adjuncts in the
      visual assessment of submacular surgery and may advance under-standing of the
      effects of submacular surgery on visual function. In addition, this testing may
      be used to plan location of surgical interventions for macular diseases.

PMID- 8865390
TI  - Polymerase chain reaction detection of cytomegalovirus and human immunodeficiency
      virus-1 in the retina of patients with acquired immune deficiency syndrome with
      and without cotton-wool spots.
AB  - PURPOSE: The authors determine the association, if any, between detection of
      human cytomegalovirus (CMV) and human immunodeficiency virus (HIV) nucleic acids
      and retinal lesions in patients with acquired immune deficiency syndrome.
      METHODS: Postmortem eyes were examined with a dissecting microscope and light
      microscopy. Retinal cotton-wool spots (CWS) were removed using a clean touch
      punch biopsy technique. Equivalent amounts of retinal tissue from the posterior
      pole of the retina not affected by CWS and from the retinal periphery also were
      studied. Polymerase chain reaction (PCR) detection of retinal cellular DNA (GA3PD
      gene), human CMV DNA (major immediate early gene), and HIV (gag gene) was
      performed using ethidium bromide and liquid hybridization detection. RESULTS:
      Ninety percent of CWS were positive for CMV DNA versus 22% of peripheral retinal
      biopsies (P < 0.025). Liquid hybridization showed similar results. Analysis of
      lesions in which results of both tests were positive (ethidium and liquid
      hybridization) versus lesions in which results of either test were negative also
      showed a strong association between CWS and CMV, but not HIV nucleic acids (P <
      0.02). Studies of HIV showed no association between retinal CWS lesions and HIV
      nucleic acid; with liquid hybridization HIV, RNA was detected equally at low
      levels in all areas. CONCLUSION: There is a statistically significant association
      between the presence of human CMV nucleic acids and retinal CWS detected by PCR.
      There is a low level presence of HIV in the retinal tissue studied that is only
      detectable using liquid hybridization techniques and is not associated with a
      particular area or lesions in the retina; this may represent detection of HIV in
      blood. The presence of CMV in areas of retinal CWS may have implications for
      their pathogenesis, but further study is necessary because other explanations are
      possible.

PMID- 8865391
TI  - Retinal detachments with crescent-shaped retinal breaks in patients with atopic
      dermatitis.
AB  - BACKGROUND: There has been increasing number of reports of retinal detachments
      associated with atopic dermatitis. However, little is known about the etiology of
      these rhegmatogenous detachments. The authors encountered two patients with
      retinal detachments associated with a crescent-shaped retinal break combined with
      another break located at or anterior to the ora. METHODS: Preoperative and
      intraoperative findings in these cases were evaluated. RESULTS: In both cases,
      vitreoretinal adhesions were observed on the anterior and posterior edges of a
      crescent-shaped retinal break. Vitreous traction between the crescent-shaped
      retinal break and the break located at or anterior to the ora was also observed.
      No abnormalities were detected in the choroid in either case. A possible
      causative factor for the retinal detachments in these patients was the habit of
      rubbing and slapping their faces, apparently to alleviate extreme itching.
      CONCLUSION: Crescent-shaped retinal breaks, which were different from
      conventional horseshoe tears or atrophic retinal holes, were an interesting and
      unusual feature of two patients with atopic dermatitis and rhegmatogenous retinal
      detachments. These crescent-shaped retinal breaks may have been caused by ocular
      contusion.

PMID- 8865392
TI  - Experimental posttraumatic Bacillus cereus endophthalmitis in a swine model.
      Efficacy of intravitreal ciprofloxacin, vancomycin, and imipenem.
AB  - PURPOSE: The authors compare the intravitreal efficacy of ciprofloxacin,
      vancomycin and imipenem, in treating experimental Bacillus cereus
      endophthalmitis. METHODS: Thirty-three Yorkshire pigs received a surgically
      induced injury to the right eye, which was then repaired and injected with 8400
      colony forming units of live B. cereus. Nine pigs received no therapy and served
      as a natural history group. Twenty-four other pigs then were randomized into a
      treatment group with ciprofloxacin (n = 6), vancomycin (n = 6), imipenem (n = 6),
      or normal saline (n = 6). Eyes were examined clinically 1, 2, 3, 4, 5, 6, 8, 12,
      and 24 hours after inoculation. After 24 hours, the eyes were enucleated for
      histologic study. RESULTS: Experimental disease was characterized by an
      aggressively developing endophthalmitis, with retinitis and vitritis developing
      at 4 hours. Histologic examination showed vitreous abscess and retinal necrosis.
      Both vancomycin- and imipenem-treated group had less inflammation and tissue
      destruction than control animals, based on the Wilcoxon rank sum test (P < 0.05).
      Ciprofloxacin-treated animals showed significantly more intraocular destruction
      and were indistinguishable from controls. CONCLUSION: Vancomycin and imipenem
      appear to limit inflammation and tissue destruction when given early in the
      course of experimental posttraumatic endophthalmitis caused by B. cereus. Results
      with ciprofloxacin are less conclusive and warrant further investigation.

PMID- 8865393
TI  - Cytomegalovirus retinitis associated with Hodgkin's disease.
AB  - BACKGROUND: Patients with intraocular involvement by Hodgkin's disease may
      present with a variety of ocular abnormalities. Intraocular infections also have
      been reported in these patients, including two cases of cytomegalovirus retinitis
      (CMV) diagnosed on postmortem examination. It often is difficult to differentiate
      between these conditions on clinical examination. METHODS: A patient with
      Hodgkin's disease presented with an atypical retinitis, vasculitis, and a serous
      macular detachment. Results of clinical examination, fluorescein angiography, and
      vitreous biopsy for culture and polymerase chain reaction (PCR) testing are
      described. RESULTS: The diagnosis of an atypical CMV retinitis simulating
      possible intraocular involvement by Hodgkin's disease was confirmed by PCR
      testing of undiluted vitreous. Intravenous therapy with foscarnet, guided by the
      results of the vitreous biopsy, resulted in resolution of the retinitis and an
      improvement in vision. CONCLUSION: Intraocular involvement by cytomegalovirus
      retinitis can simulate intraocular lymphoma in a patient with Hodgkin's disease
      Polymerase chain reaction testing was useful in establishing the diagnosis and
      guiding successful therapy in this patient.

PMID- 8865394
TI  - Cytology of metastatic cutaneous melanoma to the vitreous and retina.
AB  - PURPOSE: The authors report one patient with definitive and one patient with
      presumed metastatic cutaneous malignant melanoma to the vitreous and retina
      diagnosed by cytologic evaluation of the vitreous and subretinal fluid. METHODS:
      A diagnostic vitrectomy was performed on two patients with atypical vitreous and
      retinal infiltrates. Additionally, subretinal fluid was obtained from the second
      patient. The specimens were processed for cytologic examination. The cytology
      specimens were compared with previously excised cutaneous melanomas from the
      patients. RESULTS: Examination results showed cells in the vitreous with high
      nuclear-to-cytoplasm ratios, coarse chromatin, and intracytoplasmic melanin
      pigment granules. The cytologic features were compared with the cutaneous
      malignant melanoma, and a diagnosis of metastatic melanoma was made. One patient
      eventually required enucleation, and the metastatic tumor in the other patient
      was controlled by local irradiation. CONCLUSIONS: Cytologic evaluation of the
      vitreous and subretinal fluid is helpful in establishing a diagnosis in patients
      with metastatic cutaneous melanoma to the vitreous and retina.

PMID- 8865395
TI  - Automatic centering of the microscope image for vitreoretinal surgery.
AB  - PURPOSE: The authors report on their device, the surgical image tracker, which
      provides automatic compensation for movements of the surgical image within the
      microscope field of view, during vitreoretinal procedures. METHODS: The authors
      developed a compact device acting as an automatic image tracker, based on video
      monitoring of the surgical image and translation of the operating microscope.
      Basic components are a standard color charge-coupled device camera and a
      specifically designed frame grabber for discrimination and tracking of the target
      image. Operation of the device is fully compatible with the usual pedal
      adjustments. RESULTS: Ready, fast, and correct automatic centering of the
      microscope field of view has been achieved successfully in all typical operating
      conditions. Video recording always is equally well centered. System operation
      also is effective with panoramic optics and diffuse illumination. CONCLUSION: The
      surgical image tracker appears to be a valuable tool to obtain well auto-centered
      surgical images, eliminating a bothersome task during vitreoretinal surgery.

PMID- 8865396
TI  - Diagnostic and therapeutic challenges.

PMID- 8865397
TI  - Bilateral endogenous Escherichia coli endophthalmitis in a neonate with
      meningitis.

PMID- 8865398
TI  - Cystoid macular edema due to cytomegalovirus retinitis in a patient with acquired
      immune deficiency syndrome.

PMID- 8865399
TI  - Bilateral subretinal neovascular membrane in idiopathic juxtafoveolar
      telangiectasis.

PMID- 8865400
TI  - Epiretinal membrane formation.

PMID- 8865401
TI  - Vitrectomy alone for the management of uncomplicated recurrent retinal
      detachments.

PMID- 8865402
TI  - Bilateral macular lesions in incontinentia pigmenti.

PMID- 8865404
TI  - Vasculitis and sarcoidosis: why the connection?

PMID- 8865405
TI  - Pathology of pulmonary granulomatous vasculitis.

PMID- 8865406
TI  - Pancreatic sarcoidosis.
AB  - Sarcoidosis affects every organ in the body; the most frequently involved
      structures are the lung, lymph nodes, liver, spleen, eyes, joints and heart.
      Gastrointestinal system affliction is uncommon. The pancreas is rarely affected
      by sarcoidosis. A review of the literature revealed only 13 patients with biopsy
      proven granulomas in pancreas or peripancreatic nodes. In a review of all
      autopsies performed between 1950 and 1993 at Los Angeles County + University of
      Southern California School of Medicine, Los Angeles, USA, the authors found one
      patient with pancreatic and 5 with peripancreatic lymph node granuloma. The
      authors also describe three previously unreported cases of pancreatic
      sarcoidosis. From the discussion, a clinically useful and pragmatic profile of
      pancreatic sarcoidosis emerges. Two thirds of the patients with pancreatic
      sarcoidosis have abdominal pain, and three quarters of them have bilateral hilar
      adenopathy. The occurrence of abdominal pain in a woman with bilateral hilar
      adenopathy with or without pulmonary infiltration should lead one to think of
      pancreatic sarcoidosis. The diagnosis should be established by a tissue biopsy
      because the laboratory and radiographic techniques do not differentiate
      pancreatic sarcoidosis from other inflammatory and malignant disorders of the
      pancreas. The prognosis of pancreatic sarcoidosis is good.

PMID- 8865407
TI  - Substance P-like immunoreactive substance in bronchoalveolar lavage fluids from
      patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.
AB  - In order to find out whether substance P (SP) participates in the inflammatory
      and fibrotic processes of interstitial lung diseases or not, SP-like
      immunoreactive substance (SP-IS) concentrations in bronchoalveolar lavage (BAL)
      fluids from patients with idiopathic pulmonary fibrosis (IPF) and pulmonary
      sarcoidosis were measured using enzyme immunoassay (EIA). The mean SP-IS
      concentrations in BAL fluids from healthy nonsmokers and healthy smokers were
      0.87 +/- 0.19 and 0.98 +/- 0.23 pg/ml, respectively. The mean SP-IS concentration
      in BAL fluids from patients with IPF was 1.15 +/- 0.39 pg/ml. The value of
      patients with IPF was significantly higher than that of healthy nonsmokers (p <
      0.01). The mean SP-IS concentrations in BAL fluids from pulmonary sarcoidosis
      patients in stage I, stage II and stage III were 0.91 +/- 0.19, 0.96 +/- 0.35 and
      1.00 +/- 0.29 pg/ml, respectively. No correlation was found between SP-IS
      concentration and pulmonary functions in IPF and sarcoidosis patients. The
      present results indicate that SP may be involved in the inflammatory process in
      IPF.

PMID- 8865408
TI  - Pulmonary sarcoidosis: could mycoplasma-like organisms be a cause?
AB  - The etiology of sarcoidosis is unknown but an unusual bacterial agent is
      possible. Mycoplasma-Like Organisms [MLO] are obligate intracellular cell wall
      deficient bacteria with a distinctive ultrastructural appearance. MLO are a
      common cause of various transmissible plant diseases. Despite over 25 years of
      effort MLO remain uncultivated. Molecular biologic studies indicate MLO are only
      distantly related to extracellular cultivable mycoplasma. Diagnosis of MLO
      diseases is based chiefly on detection of the organisms in infected cells by
      electron microscopy. Recently MLO have been detected by electron microscopy
      within leucocytes in sterile inflamed aqueous and vitreous humor from patients
      with idiopathic chronic uveitis including sarcoidosis uveitis. Preliminary
      molecular biologic studies suggest that human MLO are quite closely related
      phylogenetically to plant MLO. Inoculation of human uveitis MLO into mouse
      eyelids produced chronic uveitis and lethal systemic granulomatous disease with
      MLO within leucocytes and endothelial cells in the disease sites. The MLO induced
      animal pulmonary disease resembled sarcoidosis. This report describes abnormal
      intracellular bodies consistent with MLO within leucocytes and endothelial cells
      adjacent to the granulomas in transbronchial biopsies from 9 corticosteroid
      untreated sarcoidosis patients versus none in 4 control lungs.

PMID- 8865409
TI  - Exercise and resting pulmonary function in sarcoidosis.
AB  - Patients with sarcoidosis frequently complain of exercise intolerance but reports
      of the value of static tests of pulmonary function in predicting disability have
      been contradictory. We studied 32 patients with sarcoidosis and dyspnea,
      correlating x-ray stages, spirometry and lung volume measurements with graded
      exercise testing. Patients demonstrated a reduction in maximum workload (Wmax)
      when compared to an age matched group of 7 normal subjects (p < 0.05). While
      ventilation (VEmax) at Wmax was lower in patients, when adjusted for workload
      (V/E/watt) there was relative hyperventilation (p < 0.05). Exercise induced
      arterial desaturation (PaO2 decrease) was significantly related to resting DLCO%
      predicted (r = 0.74, p < 0.05). When patients were separated into subgroups of >
      < DLCO 55% predicted, the lower diffusing capacity group had a lower Wmax and
      greater fall in exercise PaO2. Chest radiograph staging and the vital capacity
      proved to be poor predictors of exercise capacity though maximum impairment was
      associated with advanced x-ray changes and greater decreases in vital capacity.
      In conclusion, the magnitude of functional impairment may vary widely from
      apparent histopathologic involvement as reflected by chest x-ray and lung
      volumes. Actual exercise testing is necessary to accurately characterize and
      quantitate the impairment in patients with sarcoidosis complaining of dyspnea.

PMID- 8865410
TI  - Sarcoidosis and regional enteritis in two patients.
AB  - Both sarcoidosis and Crohn's disease (regional enteritis) are characterized by
      granuloma formation and they also have an unknown etiology. Only a few subjects
      with co-existing sarcoidosis and Crohn's disease have been reported in the
      literature. We report two cases who suffered from both disorders. In the two
      subjects Crohn's disease began first and the symptoms of sarcoidosis came later;
      four and sixteen years, respectively.

PMID- 8865411
TI  - Sudden hearing loss as the initial manifestation of neurosarcoidosis.
AB  - We report two cases of sudden hearing loss as the initial manifestation of
      neurosarcoidosis. The patients had no symptoms suggesting central nervous system
      or meningeal involvement. Eighth nerve involvement is an uncommon feature in
      patients with sarcoidosis. We discuss the pathophysiologic basis of sarcoid
      induced hearing loss.

PMID- 8865412
TI  - Use of lung function tests in sarcoidosis.

PMID- 8865413
TI  - The gastrointestinal tract and the lungs. Similarities with particular emphasis
      on the neuroendocrine cells.

PMID- 8865414
TI  - Chronic inflammatory diseases.

PMID- 8865415
TI  - Extracellular phospholipase A2 expression in sarcoidosis.
AB  - This study was conducted in order to focus upon the Ca2- dependent secretory non
      pancreatic phospholipase A2 (npPLA2) enzyme and its possible role in the
      pathophysiology of sarcoidosis. Serum samples were taken from 24 patients with
      sarcoidosis to determine the levels of npPLA2. Moreover, in another group of
      patients with active chest x-ray stage II and III sarcoidosis, bronchoscopy with
      bronchoalveolar lavage (BAL) and transbronchial lung biopsies (TBL) were taken.
      Highly significant increase of npPLA2 in serum was found in patients compared to
      controls (p < 0.001). Furthermore, those patients with stable and inactive
      disease and those who were under treatment with corticosteroids, tended to have
      lower values than those with active disease and those who were untreated. An
      intense accumulation of npPLA2 was found in smooth muscle tissue in lung biopsy
      specimens, in close connection with fibroblast accumulation and deposition of
      collagen. These cells also stained positive for alpha-smooth muscle actin (alpha
      SMA). In addition, when using the technique of in situ hybridization, expression
      of npPLA2-mRNA was found in the fibroblast layer surrounding the epitheloid cell
      granulomas. These fibroblasts did not stain positive for alpha-SMA. Our data
      suggest that npPLA2 is actively involved, and has an important role, in the
      pathophysiology of sarcoidosis.

PMID- 8865416
TI  - Systemic sarcoidosis with severe proliferative sarcoid retinopathy.

PMID- 8865418
TI  - Blood gases and hypothermia: some theoretical and practical considerations.
AB  - There is much controversy about the optimal bloodgas management of hypothermic
      patients, whether the hypothermia is caused by accidents or induced before
      operations. The surgeons and anestesiologists have acquired more clinical
      experience the last years when operating patients in hypothermia. The comparative
      physiology has given increased information about the blood gas strategy of
      heterothermic endotherms and poikilothermic ectotherms during lowering of their
      core temperature. There are two types of strategies which have been used in
      clinical medicine the last years in the blood gas management of patients in
      hypothermia: pH-stat method and alpha-stat method. In the pH-stat method, the
      arterial carbon dioxide tension (pCO2(a)) is maintained at 5.3 kPa (40 mmHg) and
      the pH is maintained at 7.40 when measured at the actual temperature. It is then
      necessary to add CO2 to the inspired gas. In the alpha-method, the arterial
      carbon dioxide tension and the pH are maintained at 5.3 kPa and 7.40 when
      measured at +37 degrees C. When a patient is cooled down, the pH-value will
      increase and the pCO2-value and the pO2-value will decrease with lowering of the
      temperature if measured at the patients temperature. Both the pH-stat and alpha
      stat strategies have theoretical disadvantages. For the optimal myocardial
      function the alpha-stat method is the method of choice. The pH-stat method may
      result in loss of autoregulation in the brain (coupling of the cerebral blood
      flow with the metabolic rate in the brain). By increasing the cerebral blood flow
      beyond the metabolic requirements, the pH-stat method may lead to cerebral
      microembolisation and intracranial hypertension. In Norway the alpha-stat
      strategy is the preferred method.

PMID- 8865417
TI  - The Oxygen Status Algorithm on-line with the pH-blood gas analyzer.
AB  - BACKGROUND: The Oxygen Status Algorithm is a computer program for interpretation
      of pH-blood gas measurements. Recently the facility for on-line transfer of
      measured data from the pH-blood gas analyzer (ABL 520) to the computer with
      instant calculation, graphical display, and print-out of the oxygen status and
      the acid-base status of the blood has been implemented. OBJECTIVE: To describe
      experiences with routine application of the Oxygen Status Algorithm in an
      intensive care unit and to describe recent improvements of the program. DATA
      SOURCES: Routine pH-blood gas analyses during a two year period with an average
      of 40 analyses per day. RESULTS: Several unexpected results were disclosed,
      especially with respect to abnormal haemoglobin-oxygen affinity, causing
      suspicion of low 2,3-diphosphoglycerate concentration and hypophosphatemia. The
      criteria for routine administration of oxygen could be revised on the basis of
      the oxygen extraction tension. The program was expanded to allow the printing of
      a cumulated patient report, and modified to allow calculation of the oxygen
      consumption rate on the basis of simultaneous measurements on the arterial and
      the mixed venous blood. The program and the computer hardware functioned well in
      continuous operation during the whole study. It proved to be difficult, however,
      to ensure that all measurements were supplemented by information on the patient
      temperature and the fraction of inspired oxygen. CONCLUSION: The Oxygen Status
      Algorithm provides a more detailed description of the oxygen status and the acid
      base status of the blood than currently employed. The interaction between the
      arterial oxygen tension, the haemoglobin oxygen capacity and the haemoglobin
      oxygen affinity is displayed graphically and the degree of compensation among
      these three properties is expressed in terms of a single quantity: the oxygen
      extraction tension. The program also provides an interactive interpretation,
      allowing a rapid prediction of the expected effect of therapeutic intervention.
      Nevertheless, implementation of the program in the daily routine requires an
      intensive educational effort among physicians as well as nurses and laboratory
      technicians.

PMID- 8865419
TI  - Definition, significance and measurement of quantities pertaining to the oxygen
      carrying properties of human blood.
AB  - A consistent set of definitions is given of the principal quantities pertaining
      to the oxygen transport by the blood, and of their mutual relationships, in
      relation to the methods used in their measurement. At the core is the correct
      definition of oxygen saturation, the deviation of which has recently been the
      cause of considerable confusion, especially concerning pulse oximetry. The
      occurrence, properties, determination, and pathophysiological and clinical
      significance of dyshaemoglobins, such as carboxyhemoglobin, methemoglobin, and
      sulfhemoglobin, are briefly described, together with possible consequences for
      diagnosis and therapy. In addition, attention is payed to the use of some
      haemoglobin derivatives, such as methaemoglobin and cyanmethaemoglobin, for
      clinical chemical and therapeutic purposes.

PMID- 8865421
TI  - Evaluation of protein containing quality control materials for blood gas
      analysis.
AB  - Protein containing quality control (QC) material in ampoules for blood gas, pH
      and electrolyte analysers has been manufactured using buffered protein (Bovine
      Serum Albumine, BSA) solution with sodium bicarbonate and chloride salts. For
      comparison a similar QC material but without protein was manufactured. Results
      obtained with ampouled QC material depend on pre-analytical effects, on matrix
      effects and on the stability of the material. Pre-analytical variation occurs
      with closed and/or opened ampoules. The shaking rate of the ampoule must be high
      (vortexing) and the duration of shaking long enough (15 seconds) to give good
      reproducibility. Temperature coefficients of protein containing controls are
      equal to those of protein free controls when incubated at different temperatures.
      Vigorously shaking of the ampoule gives a protein foam layer resulting in stable
      values for pH, pCO2 and pO2 during maximally 6 minutes after opening of the
      ampoule. Concerning matrix effects the CO2 buffer capacity of protein containing
      QC material is slightly higher compared to that of protein free QC materials as
      determined by tonometry with CO2/air gas mixtures and measuring pH and plotting
      log pCO2 vs. pH. The O2 buffer capacity measured as the bias on a properly
      functioning blood gas analyser is smaller than the bias of protein free QC
      material. The protein containing quality control is stable for at least 12 months
      when stored refrigerated at 2-6 degrees C and 28 days at room temperature.

PMID- 8865420
TI  - Simultaneous measurement of total hemoglobin and its derivatives in blood using
      CO-oximeters: analytical principles; their application in selecting analytical
      wavelengths and reference methods; a comparison of the results of the choices
      made.
AB  - Optical methods of quantifying total hemoglobin (tHb), applying the principles of
      the Lambert-Beer law, have been used both on untreated whole blood and on blood
      mixed with chemicals to form a stable chromophore, since the earliest days of
      laboratory medicine. The same principles may be applied for quantitation of the
      individual hemoglobin derivatives, such as oxyhemoglobin (O2Hb) and
      deoxyhemoglobin (HHb)1, as well as the non-oxygen transporting "dyshemoglobins",
      including carboxyhemoglobin (COHb) and methemoglobin (MetHb). The total
      hemoglobin measurement is typically carried out using a light source with a broad
      band of visible wavelengths. However, measurement of the derivatives requires
      using discrete, narrow bands of light in order to differentiate between the small
      differences of light absorbed by the individual derivatives. Either general
      purpose, narrow band-pass spectrophotometers, or special-purpose photometers
      utilizing a set of fixed wavelengths, commonly referred to as "CO-oximeters" are
      suitable. Rapid, direct, photometric quantification of the derivatives, necessary
      in the clinical environment, relies on the specific light absorption
      characteristics of each hemoglobin derivative at the wavelengths selected, which
      in turn requires independent and exact knowledge of the concentrations of each
      entity in reference materials. This report examines the process involved in the
      selection of wavelengths and reference methods, contrasts the effects of the
      choices made and discusses some implications and limitations for routine
      measurement.

PMID- 8865423
TI  - Comparison and assessment of blood gas related quantities including base excess,
      the gas exchange indices, and temperature corrected pH/PO2/PCO2, as defined in
      approved NCCLS standard C12-A, using a computer simulation of input variables.
AB  - Blood gases and related quantities reported to clinicians have, since the
      earliest days, included both directly measured as well as calculated or estimated
      quantities. Some developed as substitutes for quantities that were or are
      difficult to measure routinely, others to explain relationships between older,
      difficult to measure quantities and newly measureable quantities, and still
      others attempt to better understand the physiology of the acid-base process. The
      net result is a plethora of acid-base and related quantities that may be reported
      by different blood gas systems. In an attempt to address the issue of which
      quantities have stood the test of usefulness over time, and further, to examine
      the optimum algorithm for use in quantification, the NCCLS has developed, through
      its consensus process, a recommended set of quantities and their quantifying
      algorithms. We have studied these quantities and compared them with some other
      recognized approaches and present our analysis in this report. The major
      conclusion is that among those quantities recommended, the NCCLS algorithms
      present the most sensible overall approach and that we would recommend their use
      as described so that the quantities can be most effectively applied clinically,
      without differences in final values occurring due solely simple algorithm
      differences.

PMID- 8865422
TI  - Erythrocyte 2,3-diphosphoglycerate depletion associated with hypophosphatemia
      detected by routine arterial blood gas analysis.
AB  - OBJECTIVE: To describe a clinical case where an extremely low erythrocyte 2,3
      diphosphoglycerate concentration (2,3-DPG) was discovered by routine blood gas
      analysis supplemented by computer calculation of derived quantities. The finding
      of a low 2,3-DPG revealed a severe hypophosphatemia. DESIGN: Open uncontrolled
      study of a patient case. SETTING: Intensive care observation during 41 days.
      PATIENT: A 44 year old woman with an abdominal abscess. INTERVENTIONS: Surgical
      drainage, antibiotics and parenteral nutrition. MEASUREMENTS AND RESULTS: daily
      routine blood gas analyses with computer calculation of the hemoglobin oxygen
      affinity and estimation of the 2,3-DPG. An abrupt decline of 2,3-DPG was observed
      late in the course coincident with a pronounced hypophosphatemia. The fall in 2,3
      DPG was verified by enzymatic analysis. CONCLUSION: 2,3-DPG may be estimated by
      computer calculation of routine blood gas data. A low 2,3-DPG which may be
      associated with hypophosphatemia causes an unfavorable increase in hemoglobin
      oxygen affinity which reduces the oxygen release to the tissues.

PMID- 8865424
TI  - Elevations in blood lactate: overview of use in critical care.
AB  - Blood lactate measurements are being used clinically as an indicator of
      circulatory impairment and the overall state of oxygenation of patients in
      critical care. This report briefly covers the areas of usage of lactate testing,
      lactate biochemistry, appropriate sample handling, and clinical interpretation of
      lactate measurements in critical care monitoring including pediatric cardiac
      surgery and extracorporeal membrane oxygenation (ECMO).

PMID- 8865425
TI  - Biosafety implications in sample introduction: module design characteristics for
      discrete-sample systems used in critical whole blood analyte testing
      environments.
AB  - Systems designed for the measurement of pH/blood gases and expanded versions of
      these systems that include the ability to measure electrolytes or other related
      quantities, all incorporate one or more sampling modules that are limited in
      their ability to allow for the safe handling of potentially biohazardous blood
      samples. Systems that provide for injection of sample from a syringe use more
      than the required volume for sample testing and have the potential for causing
      splash-back of the sample if the introduction port is blocked. The probes of
      aspiration-based systems require manual dexterity by the operator and present the
      possibility of operator injury with a contaminated probe tip or the possibility
      of system damage as the probe extends and the operator moves the collection
      device into place. Some systems have the potential for both types of biohazards.
      This report describes the implications for system design of the sample collection
      devices commonly in use, and it offers a design solution that combines the
      ergonomics of an injection system and the operational advantages of an aspiration
      system, in combination, addressing the biosafety aspects in a unique fashion.

PMID- 8865426
TI  - Evaluation of the i-STAT portable clinical analyzer for use in a helicopter.
AB  - We evaluated the performance of the i-STAT Portable Clinical Analyzer (PCA) for
      use in a helicopter with the analyses performed by the flight nurses. Imprecision
      and initial split-sample comparative studies were performed in the Hospital
      Laboratory and Clinical Chemistry Laboratory. Day-to day imprecision (CV) ranged
      from 0.5 to 6.7% in the clinical laboratories and 0.5 to 5.3% in the helicopter
      with urea nitrogen and glucose determinations giving the highest values.
      Comparison studies between the PCA and the Kodak Ektachem E700 and the Beckman
      Astra 8 gave acceptable results, although urea nitrogen did show a bias in the
      high range (mean difference 4.91 and 3.69 mmol/L respectively). It was not
      considered medically significant for the anticipated patient population of the
      PCA in our hospitals. Comparison studies of patient specimens between the PCA in
      the helicopter and the clinical laboratories showed no significant differences,
      with the exception of glucose. Lower glucose values were obtained in the
      laboratory due to the time lag between specimen collection in the helicopter and
      analysis in the laboratory.

PMID- 8865427
TI  - A new glucose sensor for use in whole blood.
AB  - Existing electrochemical glucose sensors are either single use sensors produced
      in mass fabrication technologies or rather big sensors for multiple use with
      membranes to be changed frequently. Single use means no sensor maintenance but
      has the disadvantage that quality control measurements cannot be done with the
      same sensor used for the sample. Generally also the cost per test is relatively
      high. Multiple use sensors give the possibility of closer quality control and
      they are generally cheaper than the single use sensors for higher sample
      frequency but have the disadvantage of frequent need of remembraning. This often
      means special training and is a health risk due to sensor contamination by
      biological fluids. We combined the advantages of both principles meaning that we
      developed a new glucose sensor for multiple use in an essentially planar
      technology - thus being able to be produced very cheap. The underlying basic
      working principle is using glucose oxidase and detecting hydrogen peroxide. Due
      to the carbon base of the sensor it has a large surface area and therefore a very
      high sensitivity (microamps range at biological glucose concentrations) although
      the sensor itself is very small needing only about 10 microL of sample. The
      sensor shows a linear range of up to 40 mmol/L, a life time in use of far more
      than 1000 human serum samples and correlation coefficients between plasma and
      whole blood of r = 0.99. Interferences are well within clinical acceptability.
      Thus we conclude that this sensor works well in undiluted human body fluids and
      due to the very cheap production processes the whole sensor can be exchanged when
      it is old thus eliminating any need for remembraning or special maintenance.

PMID- 8865428
TI  - Electric potential measured, concentration reported: how to get mmols from mV.
AB  - The interdependence between the electric potential of a galvanic cell and
      concentration of electrolytes will be analyzed in order to show how a clinically
      relevant report can be obtained. The use of SI units is emphasized.

PMID- 8865429
TI  - The Ca(2+)-standardization of Japan only may cause problems for the importation
      of foreign analyzers.
AB  - A serum based reference material for Ca2+ measurement has been established in
      Japan. cCa2+ in the reference material was assigned with a IFCC reference cell.
      Some improvements of the IFCC reference cell are described. A few non-Japanese
      Ca2+ analyzers have given very inaccurate results with the reference material.
      The Japanese authorities can therefore be expected to hamper their importation in
      the future. A world-wide external quality assessment scheme with the Japanese
      reference material is suggested to further identify and solve the problems.

PMID- 8865430
TI  - International consensus on the standardization of sodium and potassium
      measurements by ion-selective electrodes in undiluted samples.
AB  - The International Federation of Clinical Chemistry (IFCC) and the National
      Committee for Clinical Laboratory Standards (NCCLS) are about to recommend to
      adjust sodium and potassium measurements by ion-selective electrodes in undiluted
      samples to the amount of substance concentration in the sample as determined,
      e.g., by flame atomic emission spectrometry. The adjustment is only valid in case
      of normal standardized sera (or plasma), implying "normal" water concentration
      (normal concentration of proteins, lipids or other macromolecules), "normal"
      binding of the pertinent electrolytes and "normal" coefficient of activity. If
      these criteria are not met, results obtained by "adjusted" ISE's will differ from
      total molar concentration. That is: in individual samples of patients results
      from ISE's and total molar concentration will differ unpredictably. It forced
      IFCC to propose new quantities for the measurements by adjusted ISE's: ionized
      sodium and ionized potassium. The reference interval for ionized sodium and
      ionized potassium is identical to the pertinent reference interval for molar
      concentration of total sodium and total potassium, but it is in contrast
      independent from water concentration and valid, e.g., in hypoproteinaemia as well
      as in hyperlipaemia or hyperproteinaemia. Accuracy control of ionized sodium and
      ionized potassium based on reference method values is hampered by abnormal water
      concentration and inadequate properties of the matrix of many control sera.
      Alternative approaches how to report measurements by ISE's in undiluted samples,
      such as activity or free molal concentration are discussed with their pros and
      cons regarding accuracy control by reference method values. The need for
      appropriate control materials with a matrix similar to native human sera is
      stressed.

PMID- 8865431
TI  - Chloride-selective electrode based on molecular oriented membrane.
AB  - In order to improve durability of chloride ion selective electrode based on
      molecular oriented membrane (MO2), a novel polymer system (MO4) was developed. In
      the polymer, ion sensitive sites are immobilized by covalent bonds to prevent
      dissolution of membrane components to sample solution. And molecular orientation
      was observed in the new system by X-ray measurement. MO4 system showed the same
      selectivity profile as the previous system with improved durability.

PMID- 8865432
TI  - A problem associated with the use of a calomel reference electrode in an ISE
      analytical system.
AB  - It was discovered during the testing of a new diluted ISE analytical system that
      a dark deposit formed in the vicinity of the reference electrode junction and on
      the junction membrane over a 1-3 month period of use. The effect of the black
      deposit was to shorten the life of the restricted flow reference membrane and
      increase the time required to maintain the system in its optimum state. Elemental
      analysis of the deposit revealed the presence of both mercury and sulfur. The
      rate of deposit build-up was found to depend on the concentrations of both the
      buffer and the microbicide in the system's reagents. The cause was traced in part
      to the generation of sulfide ions as a breakdown product of the microbicide. The
      disproportionation of calomel, Hg2Cl2, in saturated KCl to give Hg2+chloro
      complexes and their reaction with sulfide ions at the reference junction resulted
      in HgS being deposited. Design changes over previous systems contributed to the
      effect by increasing residence time of calibrant solution at the reference
      junction and decreasing the frequency of reference electrolyte and membrane
      changes. Adding complexing agents to the reference fill solution lessened but did
      not eliminate the problem. The problem was solved without reformulating the
      reagents by using a reducing agent proximate to the calomel mercury amalgam to
      reduce mercuric ions to metallic mercury. This also prevents discharge of
      environmentally undesirable mercuric ions into the waste solution.

PMID- 8865433
TI  - Accuracy evaluation and hematocrit effect of commercial ionized calcium analyzers
      using Japanese serum reference material.
AB  - The serum reference material for concentration measurement of ionized calcium in
      blood has been established by our research group in Japan. The reference method
      used is the reference standard cell (RSC:IFCC/WGSE, Covington-Umemoto Cell)
      system. Here we present the results of the evaluation of accuracy using the serum
      reference material and the hematocrit effect of the nine commercial ionized
      calcium analyzers being used in routine measurements by Japanese round robin test
      program. The ionized calcium concentration and pH of two concentration levels of
      the reference material were analyzed in triplicate measurements according to the
      standard procedures designated by manufacturers. The effect of hematocrit in
      ionized calcium concentration measurement was tested using plasma and whole blood
      with hematocrit values of 35%, 50% and 65%, respectively. The range of bias of
      ionized calcium values were -0.14 approximately +0.09 mmol/L, -0.12 approximately
      +0.09 mmol/L for ionized calcium, respectively. The effect of hematocrit in
      ionized calcium concentration measurement was strongly observed in GEM Premier,
      CAI-101 and GASTAT-2 analyzers.

PMID- 8865434
TI  - The need for protein containing quality control materials for blood pH and
      electrolyte analyzers.
AB  - In clinical chemistry quality control refers to monitoring of precision and
      accuracy of the performance of analytical methods. Calibration solutions and
      (matrixed) control solutions are used in transferring accuracy between definitive
      method, reference method and field methods. For this purpose aqueous (protein
      free), protein-containing and serum-based types of quality control materials
      having different matrices are available. Here are presented differences in
      behaviour between aqueous (protein-free) and protein-containing materials.
      Potentiometry with an electrochemical cell is an often used field method to
      determine pH and activity of electrolytes with an Ion-Selective Electrode (ISE).
      Basically, measured e.m.f.'s of calibrators and sample are translated into the
      activity of the ionic species of the sample by means of the Nernst equation.
      Besides the standard e.m.f. (E(zero)) of the electrochemical system, the measured
      e.m.f. includes the ISE-membrane e.m.f. (EISE) and depends on electrolyte type
      and its concentration and Eij depends on the composition and geometry of the salt
      bridge. Both EISE and Eij depend on the sample matrix. Protein-containing samples
      cause a negative bias on the e.m.f. at the liquid junction and a positive bias at
      the ISE. When EISE and Eij are compared to the mV span of the reference interval,
      the effects are large for Ca2+, Na+ and Cl-. Exactly the same effects exist for
      H+, K+, Li+ and Mg2+ but the inaccuracy is less critical for these ions. It may
      be concluded that only protein containing controls can detect an error that
      occurs only with measurements on plasma specimens. In practice this means that
      calibration is checked with protein-free solutions, but that measurements in
      plasma are best checked with protein-containing solutions.

PMID- 8865435
TI  - Red cell effects on lithium measurements by ion-selective electrode.
AB  - The possible interference of haematocrit was studied in an evaluation of the
      analytical performance of the NOVA 11 analyzer. For lithium concentrations
      between 0.56 and 0.68 mmol/L, the within-run imprecision was less than 1.06%, and
      less than 2.8% in day-to-day imprecision, measured in quality control solutions.
      Comparison of whole blood with plasma measurement showed satisfactory correlation
      with deviations up to 0.06 mmol/L for haematocrits from 35-53% (y = 0.73 x +
      0.12). Measurement on a blood specimen not containing lithium, whose haematocrit
      was varied, allowed us to quantify a specific red cell interference. With samples
      from treated patients, and a sample spiked to various lithium concentrations, we
      obtained differences dependent on haematocrit and on lithium concentrations. In
      subtracting the specific red cell effect, we could systematically observe that
      apparent lithium levels diminish as haematocrit increases. This observation
      should allow development of an appropriate algorithm for obtaining exact values
      on whole blood samples.

PMID- 8865436
TI  - Evaluation of syringes for ionized calcium measurements.
AB  - Commercially available ready to use syringes (Radiometer, Sarstedt, Ciba-Corning
      and Portex), containing heparinate as an anticoagulant have been tested to
      evaluate the magnitude of induced preanalytical errors. Tonometered serum pools
      adjusted to four Ca2+ concentrations were sampled anaerobically. MEASUREMENTS:
      Ca2+ and pH (ICA2 with 3 digits, Radiometer Medical A/S, Denmark; Heparin: anti
      Xa factor activity on a chromogenic substrate. Results were expressed as means of
      10 measurements and as percentages of the reference values. Sarstedt syringes,
      (Li-heparinate), yielded a negative bias (-3%). However for 0.5 or 1 mL samples
      the bias reached -4% to -6%. Radiometer syringes (QS50 and QS90; calcium titrated
      heparinate) demonstrated biases below -2%. The bias in the Ciba-Corning (Gas
      Lyte) syringe was below 2%. Portex (Pulsator) syringes showed biases above +4%
      even for nominal sampling volumes. All syringes (except Pulsator) released
      anticoagulant amounts corresponding to the expected values. Radiometer and Ciba
      Corning were the only recommendable devices.

PMID- 8865437
TI  - Comparison of precision and effect of pH and calcium on the AVL and NOVA
      magnesium ion-selective electrodes.
AB  - We compared the precision of the AVL 988-4 and NOVA CRT instruments for
      determining ionized magnesium (iMg) and assessed the effect of pH and ionized
      calcium (iCa) concentration on the results Within-run and day-to-day precision
      for the iMg electrodes were determined using three levels of control material
      supplied by each manufacturer. The effect of pH on iMg results was assessed by
      analyzing anaerobic serum samples from patients, reanalyzing those same samples
      after pH was increased by in vitro loss of CO2 and comparing the results. To
      assess the effect of iCa concentration on the iMg results, we added CaCl2 to
      aqueous standards from both manufacturers and to a normal serum pool. The results
      show comparable coefficients of variation for the two iMg electrodes both within
      run (0.68-2.05 for NOVA; 0.77-2.60 for AVL) and day-to-day (2.90-6.48 for NOVA;
      1.71-4.93 for AVL). The AVL results were not affected by the increase in serum pH
      and agreed with the NOVA results that were adjusted to a pH of 7.4 (paired t
      test; p > 0.2). There was a significant direct relationship between the iCa and
      iMg results for both analyzers, but the AVL slopes were smaller (0.026, 0.083)
      than the NOVA slopes (0.129, 0.165). Thus, these two iMg electrodes have
      comparable precision but differ in response to an increase in pH and iCa.

PMID- 8865438
TI  - Role of magnesium in patho-physiological processes and the clinical utility of
      magnesium ion selective electrodes.
AB  - Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of
      energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The
      intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA
      and RNA synthesis and structure, cell growth, reproduction, and membrane
      structure. Mg2+ has numerous physiological roles among which are control of
      neuronal activity, cardiac excitability, neuromuscular transmission, muscular
      contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+
      modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and
      endoplasmic reticular membranes. Since the turn of this century, there has been a
      steady and progressive decline of dietary Mg intake to where much of the Western
      World population is ingesting less than an optimum RDA. Geographic regions low in
      soil and water Mg demonstrate increased cardiovascular morbidity and mortality.
      Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular
      Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+
      complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical
      laboratories only now assess the total Mg, which consists of all three Mg
      fractions. Estimation of the IMg2+ level in serum or plasma by analysis of
      ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods
      employed do not distinguish the truly ionized form from Mg2+ bound to organic and
      inorganic anions. Because the levels of these ligands can vary significantly in
      numerous pathological states, it is desirable to directly measure the levels of
      IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion
      selective electrodes (ISE's), we have found that there is virtually no difference
      in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These
      data demonstrate that the mean concentration of IMg2+ in blood is about 600
      mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or
      biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and
      sera from patients with a variety of pathophysiologic and disease syndromes
      (e.g., long-term renal transplants, liver transplants, during and before cardiac
      surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non
      insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse
      [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension,
      myocardial infarction [AMI] and after excessive dietary intake of Mg), has
      revealed interesting data. The results indicate that long-term renal transplant
      patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD
      subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use
      of 31P-NMR spectroscopy on red blood cells, from several of these disease states,
      to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5
      0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in
      human volunteers, resulted in significant elevations in serum IMg2+ but not TMg.
      Correlations between the clinical course of several of the above disease
      syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio
      appears, from our data, to be an important guide for signs of peripheral
      vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data
      point to important uses for ISE's for IMg2+ in the diagnosis and treatment of
      disease states.

PMID- 8865439
TI  - Ionized magnesium concentration during liver transplantation, resection of the
      liver and cardiac surgery.
AB  - In this study we investigated three groups of patients, the first undergoing
      liver transplantation (n = 9), the second resection of the liver (n = 7) and the
      third cardiac surgery (n = 10) with regard to changes of ionized and total
      magnesium concentration during operation. Liver transplantation: Ionized
      magnesium concentration decreased from 0.58 mmol/L to 0.34 mmol/L far below the
      reference interval (0.49-0.72 mmol/L), whereas total magnesium concentration
      changed only from 0.78 mmol/L to 0.67 mmol/L (reference interval: 0.65-1.05
      mmol/L). Citrate concentration increased from 220 mumol/L to 1925 mumol/L
      (anhepatic stage) because of massive transfusion of blood products. It was
      inversely correlated to ionized magnesium concentration. Resection of the liver:
      There was a decline of ionized magnesium from 0.56 mmol/L to 0.43 mmol/L, which
      slightly exceeded the decline of total magnesium from 0.74 mmol/L to 0.64 mmol/L.
      Citrate concentration increased moderately even in cases, when no citrate was
      administered reflecting reduced hepatic function during operation. Cardiac
      surgery: Only in patients, to whom citrate but not magnesium was infused, ionized
      magnesium concentration fell slightly below the reference interval (0.45 mmol/L).
      In the other patients, to whom magnesium was administered, ionized magnesium
      concentration was within the reference interval or exceeded it. It is concluded
      that in patients with impaired hepatic function and/or high citrate load the
      monitoring of ionized magnesium concentration is mandatory.

PMID- 8865440
TI  - Changes in plasma ionized calcium and magnesium in blood donors after donation of
      450 mL blood. Effects of hemodilution and Donnan equilibrium.
AB  - The plasma concentration of ionized calcium and ionized magnesium in 26 blood
      donors decreased 0.01 mmol/L during blood donation. The changes could be
      explained by admixture of interstitial fluid. About 162 mL or 36% of the donated
      blood was replaced by interstitial fluid during blood donation. From the changes
      in concentration and hematocrit we could estimate the composition of the added
      fluid. The concentration of protein was much lower than in plasma. The
      concentration of protein-bound and free cations was also lower, in accord with
      the Donnan theory. We conclude that blood donors immediately after blood donation
      are unsuited as a reference population for proteins and ions.

PMID- 8865441
TI  - Relationship between ionized and total magnesium in serum.
AB  - The relationship between the concentration of ionized magnesium and total
      magnesium was investigated. Ionized magnesium was determined by an ion-selective
      electrode (Microlyte 6, KONE) and the result was adjusted to pH 7.4. Total
      magnesium concentration was measured by flame atomic absorption spectrometry.
      Total and ionized magnesium were only closely related in marked hypermagnesaemia
      (> 1.2 mmol/L), but correlation was poor in samples with slightly elevated total
      concentration or in hypomagnesaemia (< 0.65 mmol/L). The relationship was
      dependent on protein concentration. The agreement between total and ionized
      magnesium was acceptable in normoproteinaemia, but in hypoproteinaemia (< 40 g/L)
      total magnesium concentration was classified in 35% of the samples as below or
      within the reference interval, whereas the pertinent ionized magnesium
      concentration was normal or elevated, instead. Studies on paraproteinaemic sera
      clearly demonstrated that albumin concentration is most important for the size of
      the protein bound fraction.

PMID- 8865442
TI  - Measurement of ionized magnesium with AVL 988/4 electrolyte analyzer: preliminary
      analytical and clinical results.
AB  - Only free magnesium has biological activity: technology for measuring the ionized
      fraction of magnesium is now available via ion-selective electrodes. We have
      evaluated an instrument (AVL 988/4) which determines ionized magnesium (cMg2+)
      with an ion-selective electrode based on the ionophore ETH 7025. The selectivity
      of the electrode is adequate for the ions normally present in plasma, except for
      calcium: the interference is automatically corrected by simultaneous measurements
      of calcium with compensation for the calcium interference to the magnesium
      signal. We have first verified possible interference caused by sampling
      procedures: known silicon interference has been avoided by use of glass tubes (BD
      Vacutainer with no additive, code 7626); heparin interference has been measured
      and found significant above 20 UI.mL-1 of plasma. Instrument evaluation according
      to NCCLS protocol gives the following imprecision results on 20 replicated
      analyses: cMg2+ (mmol.L-1) 1.29, 0.76, 0.23, CVs% (within-run) 0.67, 0.67, 3.00
      and CVs% (between-run) 4.06, 3.91, 5.89 respectively. Linearity (in the range
      0.23-1.60 mmol.L-1) was: measured cMg2+ = 0.981.(calculated cMg2+) + 0.009
      mmol/L; r = 0.999. In healthy adults (n = 103) cMg2+ was in the range 0.46-0.74
      mmol.L-1 (with a mean of 0.60 mmol/L and normal distribution). These values
      represent 57% to 84% of serum total magnesium concentration (TMg) (mean 71%). pH
      dependence of cMg2+ is present, usually to a lower extent with respect to cCa2+,
      but it seems different in patients with real or in vitro provoked acidosis and in
      hemodialyzed patients. Citrate interference on ionized magnesium measurements was
      found both in vitro and in vivo, whilst that due to lactate was demonstrated only
      in vitro. On a wide range of cMg2+ (n = 100), a good correlation is obtained both
      with TMg and ultrafiltrable Mg (UFMg): cMg2+ = 0.723.TMg + 0.008 mmol.L-1, r =
      0.978; cMg2+ = 0.912.UFMg + 0.10 mmol.L-1, r = 0.968, respectively. The ionized
      magnesium in ultrafiltrate was found 25% lower than that in serum. The lifespan
      of the electrode, evaluated on the basis of both time from installation and on
      number of measured samples, was estimated longer than 4 months and able to
      analyze more than 1500 samples, whichever comes first. The four electrodes we
      used during 18 months behaved all the same way. The correlation between
      measurements performed in whole blood (WB-cMg2+) and in the corresponding serum
      (S-cMg2+) was excellent: WB-cMg2+ = 0.954.S-cMg2+ +0.02 mmol.L-1; r = 0.998; n =
      60.

PMID- 8865443
TI  - More on the measurement of ionized magnesium in whole blood.
AB  - Current technology has made it possible to measure ionized magnesium with user
      friendly ion selective electrode technology. Although this technology has not
      reached a perfect status literature shows that it can be used in clinical routine
      especially in serum. This paper deals with issues concerning the measurement of
      ionized magnesium in whole blood. To measure in whole blood apart from an
      instrument with good general performance data an adequate sample treatment is
      especially critical. We tested a number of different sample containers and found
      that they interfere in different degrees with the magnesium determination. In
      some cases this is due to silicone giving falsely high ionized magnesium values
      which may be twice the real value and even higher. Another problem is the
      heparinization of the sample. We found that different heparins may alter the
      result in a different way. The well known complexing capability of heparin may
      lead to a reduction of the ionized magnesium within the sample and thus to false
      low results. But some heparins cause elevated results. The reason for this may be
      zinc. Test procedures to check the quality of anticoagulants are given. Due to
      these procedures sample containers could be found which do not interfere with the
      determination of ionized magnesium in whole blood - thus making the measurement
      possible. All these factors indicate that the measurement of ionized magnesium
      really needs a very well defined sample handling - otherwise false results may
      arise. This is not only true for the measurement of whole blood but also for
      plasma or even for "so called serum" as there might be a sample container within
      the chain from patient to the instrument which is unsuitable- and thus will alter
      the result.

PMID- 8865444
TI  - Dual and triple therapy regimens of antisecretory agents and antibiotics for the
      eradication of Helicobacter pylori: an overview.
AB  - BACKGROUND: Studies evaluating therapeutic regimens that combine antisecretory
      agents with antibiotics for the eradication of H. pylori have reported
      significant variations in efficacy. METHODS: We reviewed the published literature
      to compare H. pylori eradication rates in patients treated with either
      omeprazole, ranitidine bismuth citrate (RBC), or ranitidine plus metronidazole
      combined with either amoxicillin or clarithromycin. RESULTS: Wide variations in
      H. pylori eradication rates have been reported with omeprazole plus either
      amoxicillin (0-100%) or clarithromycin (42-88%). Eradication rates ranging from
      45% to 89% and from 74% to 94% have been reported with RBC plus either
      amoxicillin or clarithromycin, respectively. Eradication rates ranging from 48%
      to 90% have been reported with ranitidine plus metronidazole and amoxicillin and
      one study reported an eradication rate of 95% with ranitidine plus metronidazole
      and clarithromycin CONCLUSIONS: Well-controlled trials with ranitidine bismuth
      citrate plus clarithromycin suggest that this combination may provide the most
      consistent and effective regimen for the eradication of H. pylori infection.

PMID- 8865445
TI  - Gastro-oesophageal reflux disease in The Netherlands. Results of a multicentre pH
      study.
AB  - Information on the relationships between gastro-oesophageal reflux (GOR), reflux
      symptoms, hiatal hernia (HH) and oesophagitis, and the response to antisecretory
      treatment is lacking. In a multicentre study endoscopy, ambulatory 24-h pH
      monitoring and symptom assessment were carried out in 142 patients with
      symptomatic reflux disease before and during treatment with ranitidine. Using a
      randomized, double-blind design, patients took ranitidine 150 mg bid or 300 mg
      bid. Macroscopic oesophagitis (grade I or II) was found in 85 patients; the
      remaining 57 patients had normal oesophageal mucosa. A significant correlation
      was found between the presence of an HH and the presence of oesophagitis. Symptom
      scores were similar in patients with and without oesophagitis, and in patients
      with and without HH. Patients with oesophagitis had significantly greater
      oesophageal acid exposure during the night, and in the total 24-h period, but not
      during the day. Likewise, patients with HH had greater acid exposure during the
      night (p < 0.008). Both doses of ranitidine significantly decreased oesophageal
      acid exposure and the effect was independent of baseline acid exposure. Reflux
      symptoms cannot be used to differentiate between presence or absence of
      oesophagitis and/or HH. Reflux patients without oesophagitis have less night-time
      reflux. Ranitidine dose-dependently decreases oesophageal acid exposure, and the
      effect is independent of baseline reflux.

PMID- 8865446
TI  - A review on treatment of bleeding peptic ulcer: a collaborative task of
      gastroenterologist and surgeon.
AB  - The majority of patients presenting with acute upper gastrointestinal haemorrhage
      bleed from peptic diseases erosive gastritis and duodenal or gastric ulcers.
      Early gastroscopy is essential in order to reach a diagnosis, assess the
      prognosis, and institute appropriate therapy. In a meta-analysis it was shown
      that H2-antagonists significantly reduced mortality. However, two large,
      prospective and placebo-controlled studies with famotidine and omeprazole failed
      to show reduction of rebleeding or death. The value of endoscopic haemostatic
      therapy in patients with high-risk peptic ulcers (active bleeding and non
      bleeding visible vessel) has been firmly established with 75% decrease in
      rebleeding and operation rate, and a 40% reduction in mortality. Risk factors for
      an adverse outcome are: elderly patients, concomitant diseases and large ulcers
      in the posterior duodenal bulb or on the lesser curvature. The mortality for
      emergency surgery in upper GI bleeding is still 10-50%. The mortality of elective
      operations is less than 2%. Some studies have reduced mortality by avoiding
      emergency surgery through early elective surgery in high-risk patients.

PMID- 8865447
TI  - Nutrient malassimilation following total gastrectomy.
AB  - BACKGROUND: The aim of the study was to elucidate the degree and the
      pathophysiology of abdominal symptoms, malnutrition and malassimilation after
      total gastrectomy. METHODS: In 174 consecutive patients, with potentially
      curative total gastrectomy for gastric malignancy, subjective symptoms and
      objective parameters of malassimilation were evaluated. RESULTS: Abdominal
      symptoms were present in 86% of the patients. In spite of a high daily calorie
      intake (median 37.8 kcal/kg body weight) mean body mass index had been decreasing
      since good health. Anaemia was found in 46%, sideropenia in 31% and oesophagitis
      in 26%. Mean faecal fat excretion was 17.4 (1.4) g/day and mean fat
      malassimilation 14.8% (1.1) of the intake. A shortened small-bowel transit was
      measured in 21.7% of the patients, and bacterial overgrowth was present in 37.7%.
      CONCLUSIONS: Malassimilation post total gastrectomy seems to be multifactorial.
      Shortened small-bowel transit and subsequent dyssynchrony of pancreatic enzyme
      supply seem to be of major importance.

PMID- 8865448
TI  - Sphincter-saving surgery for rectal and colorectal disorders.
AB  - BACKGROUND: Restoration of intestinal continuity by anal anastomosis after
      sphincter-saving rectal excision is feasible from an oncological, technical and
      functional standpoint. We present our experience. METHODS: The records of 223
      patients with an anal anastomosis were reviewed. The anal anastomosis was
      performed hand-sutured transanally in 92 patients and double-stapled
      transabdominally in 131 patients. Coloanal anastomosis was performed in 39
      patients and ileoanal pouch anastomosis in 184 patients. RESULTS: Operation time,
      blood loss and admission times were considerably less after double-stapling
      anastomosis. Relevant complications occurred in 15% after coloanal anastomosis
      and in 35% after ileoanal pouch anastomosis, failure rate was similar (13%).
      Complication (7% vs 43%) and failure rate (2% vs 27%) were less after double
      stapled anastomosis. Prednisone did not influence the failure rate whereas
      previous abdominal surgery did. CONCLUSIONS: The double-stapling technique gives
      less complications and better results although effects of a learning curve are
      undoubtedly present in this series. The technique makes a temporary diverting
      ileostomy superfluous. The double-stapling technique is to be preferred for anal
      anastomoses.

PMID- 8865449
TI  - Spontaneous bacterial peritonitis: an indication for liver transplantation?
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication in
      patients with cirrhosis and ascites with a poor prognosis. The survival pattern
      and the reasons for not performing a liver transplantation after an episode of
      SBP were analysed. METHODS: A retrospective analysis during the period 1987-1992
      in a tertiary referral and liver transplantation centre. RESULTS: Sixty episodes
      of SBP were diagnosed in 52 patients with ascites. Thirty-two percent of the
      patients died within 30 days and 78% within 1 year. Forty patients who survived
      less than 1 year did not receive a liver transplantation for the following
      reasons: death within 30 days (n = 12), age above 65 years (n = 10), medical
      contraindications (n = 6), active alcohol abuse (n = 6), refusal of
      transplantation (n = 2), death while being analysed for, or awaiting
      transplantation (n = 4). Two patients had an auxiliary liver transplantation but
      died postoperatively. CONCLUSION: SBP is a serious complication in patients with
      cirrhosis and ascites, with a high first-year mortality and a high recurrence
      rate. Although long-term survival after an episode of SBP is possible, liver
      transplantation should be considered for the patients with a progressive liver
      disease after a first episode of SBP.

PMID- 8865450
TI  - Laparoscopic ultrasonography for staging of gastrointestinal malignancy.
AB  - BACKGROUND: Diagnostic laparoscopy has been used frequently as a preoperative
      staging procedure for different gastrointestinal malignancies. The assessment of
      solid abdominal organs and retroperitoneal ingrowth or detection of lymph-node
      metastasis is limited, however. A recent development, laparoscopic
      ultrasonography, will probably increase the preoperative evaluation of these
      lesions and thus further improve the preoperative staging. METHOD: Since 1993
      diagnostic laparoscopy combined with laparoscopic ultrasonography has been
      performed as an additional diagnostic procedure in patients who have already been
      selected for curative resection of different GI malignancies. In this prospective
      study, staging after conventional work-up is compared with the tumour stage after
      laparoscopy. All patients underwent exploratory laparotomy except those with
      histologically proven metastases/ingrowth. RESULTS: For patients with cancer of
      the esophagus and gastric cardia (n = 56) the preoperative stage was altered in
      17% but laparotomy could only be avoided in 5% (for a subgroup of patients with a
      tumour of the gastric cardia laparotomy was avoided in 11%). Additional findings
      during laparoscopy showed that laparotomy could be avoided in 55% of the patients
      (n = 44) with primary liver tumours, liver metastasis or proximal bile duct
      tumours. For patients with pancreatic head tumours (n = 73) the preoperative
      stage of the tumor changed in 40%; the strategy of treatment was changed in 26%
      and laparotomy could be avoided in 20%. CONCLUSIONS: Laparoscopy combined with
      laparoscopic ultrasonography is effective (more accurate) in the staging of
      gastrointestinal malignancies, in particular for patients with liver, biliary and
      pancreatic tumours. The preoperative tumour stage changed between 15 and 60% for
      the different gastrointestinal malignancies and laparotomy could be avoided in 5
      55%. The procedure is highly operator-dependent and has a learning curve.

PMID- 8865451
TI  - Effects of parenteral nutrients on gastrointestinal motility and secretion.
AB  - BACKGROUND: The stimulation of gastrointestinal motility and secretion during
      nutrient digestion is generally divided into a cephalic, gastric and intestinal
      phase. Little is known about the effects of macronutrients on gastrointestinal
      function during the postabsorptive or circulatory phase of digestion. METHODS:
      Review of studies investigating the effects of circulating macro-nutrients such
      as fat, amino acids and glucose on gastrointestinal motility and secretion.
      RESULTS: Intravenous infusion of fat emulsions delays gastric emptying and
      interrupts the interdigestive intestinal motor pattern. Intravenous amino acids,
      administered in high doses, stimulate gastric acid secretion, pancreatic
      secretion, gallbladder contraction, and intestinal motility. Patients receiving
      total parental nutrition (TPN) have inert gallbladders and are at risk of
      developing gallbladder sludge and stones. Administering a proportion of the daily
      amino acid requirement by rapid intravenous infusion may prove useful in the
      prevention of sludge and stone formation during TPN by promoting gallbladder
      contraction. Intravenous infusion of glucose, already at physiological
      postprandial plasma levels, inhibits gastrointestinal motility and secretion. The
      inhibitory effect of glucose is dose-dependent, that is, more pronounced at
      higher plasma glucose levels. Recent studies have indicated that in patients with
      diabetes mellitus alterations in gastrointestinal function are related to the
      degree of hyperglycaemia. CONCLUSIONS: Nutrients during the circulatory phase of
      digestion influence gastrointestinal motility and secretion. Knowledge of these
      effects is relevant for conditions with increased plasma levels of macro
      nutrients such as in patients with diabetes mellitus or during total parenteral
      nutrition.

PMID- 8865452
TI  - Cholesterol synthesis inhibitors in cholesterol gallstone disease.
AB  - Cholesterol synthesis inhibitors (HMG-CoA Reductase Inhibitors) are reported to
      decrease cholesterol saturation index of duodenal bile in hypercholesterolaemic
      subjects. The dissolution of gallstones in animals on treatment with these drugs
      created expectations of a therapeutical role for these drugs in cholesterol
      gallstone disease. However, in prospective studies with these drugs in humans, no
      effect on number and size of cholesterol gallstones was observed. This is likely
      the result of the fact that not just biliary secretion of cholesterol is
      decreased during treatment with these drugs in cholesterol gallstone disease, but
      phospholipids and bile salts as well. As a consequence, nucleation time of
      cholesterol crystals in gallbladder bile is not influenced by these drugs.
      Another important determinant in cholesterol gallstone disease, e.g. gallbladder
      motility, is not influenced by HMG-CoA reductase inhibitors. Although these drugs
      and their metabolites are secreted into the bile, they do not influence biliary
      lithogenicity. In conclusion, there seems to be no therapeutic role for HMG-CoA
      reductase inhibitors in the treatment of cholesterol gallstone disease, although
      no negative effects on determinants of cholesterol gallstone formation during
      treatment with these drugs are observed either.

PMID- 8865454
TI  - Anal fissure: new concepts in pathogenesis and treatment.
AB  - The posterior commissure of the anal canal is less well perfused than the other
      segments of the anoderm. There is growing evidence that the increased activity of
      the internal anal sphincter, which is found in almost all patients with a chronic
      anal fissure, further decreases the anodermal blood supply, especially at the
      posterior midline. Reduction of anal pressure, either by anal dilatation or by
      lateral internal sphincterotomy, is the most important step in the treatment of
      chronic anal fissure. However, both procedures frequently result in permanent
      sphincter defects and subsequent continence disturbances. Recently, nitric oxide
      (NO) has been identified as the chemical messenger mediating relaxation of the
      internal anal sphincter. It has been shown that local application of exogenous NO
      donors such as nitroglycerin and isosorbide-di-nitrate reduces anal pressure and
      improves anodermal blood flow. This dual effect results in fissure healing in
      more than 80% of patients.

PMID- 8865453
TI  - Ammonia and glutamine metabolism during liver insufficiency: the role of kidney
      and brain in interorgan nitrogen exchange.
AB  - BACKGROUND: During liver failure, urea synthesis capacity is impaired. In this
      situation the most important alternative pathway for ammonia detoxification is
      the formation of glutamine from ammonia and glutamate. Information is lacking
      about the quantitative and qualitative role of kidney and brain in ammonia
      detoxification during liver failure. METHODS: This review is based on own
      experiments considered against literature data. RESULTS AND CONCLUSIONS: Brain
      detoxifies ammonia during liver failure by ammonia uptake from the blood,
      glutamine synthesis and subsequent glutamine release into the blood. Although
      quantitatively unimportant, this may be qualitatively important, because it may
      influence metabolic and/or neurotransmitter glutamate concentrations. The kidney
      plays an important role in adaptation to hyperammonaemia by reversing the ratio
      of ammonia excreted in the urine versus ammonia released into the blood from 0.5
      to 2. Thus, the kidney changes into an organ that netto removes ammonia from the
      body as opposed to the normal situation in which it adds ammonia to the body
      pools.

PMID- 8865455
TI  - The role of endosonography in esophageal carcinoma: who should get it, who should
      do it?

PMID- 8865456
TI  - Mucosal inflammation and disease in Helicobacter pylori infection.
AB  - The discovery of Helicobacter pylori as an important gastric pathogen and as one
      of the most common bacterial infections, now more than a decade ago, completely
      changed our concepts of both gastroduodenal disease and the immunobiology of the
      stomach. At this moment, H. pylori is recognized as the cause of chronic
      gastritis, peptic ulcer disease, and as an important causal factor in the chain
      of events leading to gastric carcinoma. Before H. pylori can lead to gastritis
      and a chronic immune response the bacterium has to evade and subsequently to
      interact with the mucosal defence mechanisms. After colonization of the gastric
      mucosa by H. pylori the persistent presence and survival of the bacterium leads
      to a chronic local and systemic immune response. Recent developments and insights
      into the gastric mucosal inflammation caused by H. pylori and its pathogenic
      mechanisms are the subject of this review.

PMID- 8865457
TI  - Recent developments in hereditary nonpolyposis colorectal cancer.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is characterized
      by early onset of colorectal carcinoma (CRC), usually located proximally to the
      splenic flexure and reportedly carrying a better survival as compared to sporadic
      type CRC. Depending on the absence or presence of extracolonic tumours,
      particularly carcinomas of the endometrium, stomach and urinary tract, HNPCC can
      be divided into Lynch syndromes I and II, respectively. Although first described
      in 1913, the elucidation of the molecular basis of this disease has only recently
      started to unfold, and is reviewed in this article. METHODS: Literature survey of
      published articles. RESULTS: Comparison of HNPCC tumours with sporadic-type CRC
      had already revealed that no significant differences were found in APC, Ki-ras
      and p53 gene alterations. Instead, microsatellite instability was found to be the
      hallmark of HNPCC being present in 80% of cases compared to only 13% of sporadic
      type CRC. Since studies in yeast and bacteria had shown that microsatellite
      instability resulted from mutations in so-called postreplicative DNA mismatch
      repair genes, it was hypothesized that a similar mechanism might underlie the
      observed microsatellite instability in HNPCC and, hence, its hereditary
      character. In due course, four human homologues of yeast and bacterial
      postreplicative DNA mismatch repair genes were cloned and denoted hMSH2, hMLH1,
      hPMS1, and hPMS2. Current estimates suggest that mutations in hMSH2 account for
      50%, in hMLH1 for 30%, in hPMS1 for 5% and in hPMS2 for 5% of HNPCC. CONCLUSIONS:
      Despite many issues still to be resolved, accurate molecular screening tests will
      in all probability become the gold standard in the diagnosis of HNPCC. As a
      result, these developments will undoubtedly have profound implications for early
      detection and subsequent management of affected individuals.

PMID- 8865458
TI  - Primary sclerosing cholangitis and liver transplantation.
AB  - Primary sclerosing cholangitis is a chronic disease, strongly associated with
      ulcerative colitis and cholangiocarcinoma. Ulcerative colitis itself does not
      influence the liver transplant results. However, intensified screening after
      liver transplantation for carcinoma of the colon may be necessary.
      Cholangiocarcinoma, although incidentally found in hepatectomy specimens, has a
      bad prognosis. Initial reports in the literature indicate a far lower survival
      when liver transplantation is performed for PSC, in comparison to the results
      achieved in other transplant indications. This might have been due to surgical
      interventions which nowadays are avoided. Later reports show a better prognosis
      than the initial ones. We report on the results of liver transplantation for PSC,
      as indicated in the literature and on the results of the Groningen transplant
      centre.

PMID- 8865459
TI  - Helicobacter pylori and gastric carcinogenesis.
AB  - BACKGROUND: Helicobacter pylori causes chronic persistent gastritis in virtually
      all infected subjects, leading to development of atrophic gastritis, intestinal
      metaplasia and eventually dysplasia and gastric cancer in a number of infected
      subjects. Based on the available evidence, an IARC monograph committee classified
      H. pylori as a class I carcinogen to humans. Prospective studies suggest that
      infection increases the risk for atrophic gastritis and gastric cancer at least 8
      fold. In the presence of infection, the risk for atrophy and cancer seems higher
      if a subject becomes infected in early childhood, if infection occurs with a cagA
      positive strain, and if acid output is decreased. CONCLUSION: H.pylori is a
      gastric carcinogen. The clinical implications and possible strategies for cancer
      prevention have to be delineated in the near future.

PMID- 8865460
TI  - Hepatitis C virus: biological and clinical consequences of genetic heterogeneity.
AB  - Hepatitis C Virus infection accounts for the majority of post-transfusion and
      sporadic hepatitis. In Western Europe, anti-HCV is detected in 0.4-1.5% of
      healthy blood donors. There is a high frequency of progressive chronic hepatitis,
      ranging from 50 to 80%, which leads to cirrhosis in 20-50% of patients after 10
      20 years. Viremic patients with minimal biochemical abnormalities may have
      chronic liver disease histologically. There is growing evidence that virological
      features of HCV are associated with different clinical manifestations and
      response to therapy. The RNA genome consists of a 5' and 3' Untranslated Region,
      a structural domain encoding the core and envelope proteins, and a non-structural
      domain. Different HCV isolates show a high sequence heterogeneity, which has led
      to the classification of currently six genotypes and several subtypes. There is a
      marked difference in the geographic distribution of HCV genotypes, with types 1,
      2 and 3a being most frequently found in western countries. In The Netherlands,
      subtype 1b accounts for approximately 60% of all cases of chronic HCV. Serologic
      diagnosis based on recombinant C-100 antigens (first generation immunoassays)
      only reliably detected type 1, due to the heterogeneity of the NS4 region;
      inclusion of more conserved proteins c22 and c33 (second generation assays) has
      largely improved sensitivity of anti-HCV testing. Genotype 1b is associated with
      more severe liver disease and with lower response rates for antiviral therapy,
      compared with types 2 and 3. Quasispecies nature and escape mutants may enable
      viral persistence and the development of chronic liver disease. As cross
      reactivity between genotypes is unlikely, prevention of HCV disease may be
      dependent on the development of multivalent vaccines.

PMID- 8865461
TI  - New approaches to endoscopic therapy for a haemostasis upper GI bleed.
AB  - Haematemesis and/or melaena are the most common presentations of upper
      gastrointestinal bleeding. Endoscopic haemostasis after diagnosis still remains a
      challenge to the gastroenterologist. Most variceal and peptic ulcer bleeding
      episodes stop spontaneously, and then prevention of rebleeding might be indicated
      by endoscopic techniques. In the present article, four less well-known endoscopic
      haemostasis techniques are discussed and, if available, comparative studies are
      reviewed.

PMID- 8865462
TI  - Intracellular transport of pancreatic enzymes.
AB  - Most pancreatic secretory proteins are packaged within the trans-Golgi network
      into zymogen granules, which are secreted in a regulated manner by exocytosis.
      But others enter alternative, constitutive-like pathways directed towards both
      apical and basolateral membranes. Our in-vivo studies suggest that secretion via
      the latter type of pathway, which may be responsible for the appearance of
      pancreatic enzymes in the circulation, can be increased by stimulation,
      especially supramaximal stimulation. This may partly explain the increased
      concentration of pancreatic enzymes in the circulation in the early stages of
      pancreatitis. The mechanisms by which secretory proteins are sorted into zymogen
      granules remain vague. However, dissipation of the normally acidic gradient
      across the trans-Golgi network in vitro (e.g. with NH4Cl) inhibits the process by
      which newly synthesized proteins reach zymogen granules. However, secretion via
      the constitutive-like pathways is apparently not increased under these
      conditions. Thus, although the acidic milieu of the trans-Golgi network plays a
      role in pancreatic protein sorting, it may not be the mechanism by which
      constitutive-like secretion of pancreatic enzymes is increased.

PMID- 8865463
TI  - Experimental models of acute pancreatitis and their relevance to human disease.
AB  - There are no experimental models which mimic the most common causes of human
      acute pancreatitis, i.e. gallstones and alcohol abuse. However, existing models
      can reproduce the morphology and physiological derangements of certain phases of
      the illness. Current models have been useful in elucidating the earliest events
      involved in the initiation and progression of pancreatitis. However, very few
      animal studies demonstrate effective therapeutic intervention when treatment is
      given after the induction of experimental pancreatitis. Since immediate
      intervention is unachievable in human disease, most experimental therapies have
      not been successfully applied to clinical disease.

PMID- 8865464
TI  - Role of oxidative stress in the pathogenesis of acute pancreatitis.
AB  - During the last 10 years, the role of oxidative stress in pancreatitis and the
      benefits or otherwise of antioxidants has been the subject of numerous research
      papers. There is general agreement that glutathione and other sulphydryl
      compounds are depleted while lipid peroxidation is increased in pancreatic tissue
      during the development of acute pancreatitis. Treatment with antioxidants has
      been shown to reduce acinar cell injury and oedema in various animal models of
      pancreatitis, suggesting that the sustained generation of reactive oxygen species
      depletes cellular antioxidant defences. Evidence for a role for bradykinin and
      nitric oxide in pancreatitis has been conflicting with some studies suggesting
      these agents might ameliorate pancreatic dysfunction by enhancing pancreatic
      blood flow and secretion in response to bradykinin-stimulated generation of
      nitric oxide from endothelium, while other studies suggest that nitric oxide
      potentiates pancreatic oxidative stress. Thus, there is clearly a need for well
      designed clinical trials to evaluate the protective role of antioxidant therapy
      in acute pancreatitis.

PMID- 8865465
TI  - Circulating mediators in acute pancreatitis as predictors of severity.
AB  - The case mortality for acute pancreatitis in the UK has remained largely
      unchanged, at just under 10% for the last 30 years. This is despite improvements
      in intensive therapy, radiology and surgical interventions. Acute pancreatitis
      also remains unpredictable. Organ system failure and pancreatic collections may
      develop either suddenly, or insidiously, and thus go undetected. Reducing
      mortality depends on better understanding of pathophysiology and more specific
      therapeutic approaches, but prognostic systems for the early identification of
      severe attacks may improve the success of current supportive therapies.
      Prognostic systems are also useful to compare clinical series and stratify
      severity in therapeutic trials. The multiple criteria of Ranson and Imrie
      predominate, but offer limited accuracy, involve delay, are cumbersome, and
      provide a one-off overall prediction. Internationally agreed definitions of
      complications demand accurate risk assessment for individual complications, while
      serial monitoring of severity is needed to assess progress and to detect subtle
      changes after therapeutic intervention. Laboratory methods now provide equal, or
      improved, accuracy and speed compared to traditional criteria, and may be
      repeated serially. Growing knowledge of the systemic inflammatory response
      syndrome (SIRS) and the availability of response modifiers suggests that
      inflammatory mediators may prove to be the most useful and accurate means of
      assessment of severity.

PMID- 8865466
TI  - Ischaemia-reperfusion mechanisms in acute pancreatitis.
AB  - The role of ischaemia in the pathogenesis of acute pancreatitis is unknown. Some
      experimental studies have shown that ischaemia has little effect on the pancreas,
      while others have found an association with pancreatic injury. Ischaemia
      reperfusion damage has been well documented in other sites such as the intestine,
      cardiac muscle, and skeletal muscle. However, in the pancreas, injury is usually
      seen only after complete ischaemia, which is uncommon clinically. Experimental
      chronic pancreatitis is characterized by low pancreatic blood flow, low
      interstitial pH, and impaired pancreatic tissue oxygenation, which are all
      findings consistent with the ischaemia-reperfusion mechanisms. Acute pancreatitis
      is also associated with a reduction in pancreatic blood flow and evidence of free
      radical generation, similarly suggesting the possibility of ischaemia-reperfusion
      injury. Ethanol ingestion, which is commonly associated clinically with both
      chronic and acute pancreatitis, may itself contribute to an ischaemic-reperfusion
      injury. We have shown that administration of ethanol to cats decreases pancreatic
      blood flow and may also directly activate neutrophils. Further investigation is
      needed to determine whether or not these findings are also associated with an
      ischaemia-reperfusion injury.

PMID- 8865468
TI  - Platelet-activating factor.
AB  - Platelet-activating factor (PAF) is a proinflammatory lipid. It has been strongly
      implicated in the regulation of pancreatic exocrine secretion and in the local
      and systemic events which occur in acute pancreatitis. PAF antagonists, when
      given as pretreatment, ameliorate the severity of experimental acute pancreatitis
      by reducing serum amylase, oxidative injury, morphological changes, polymorph
      infiltration, pulmonary damage, and exudative levels of PAF in blood and
      peritoneal fluid. The novel, potent PAF antagonist, lexipafant, can ameliorate
      microvascular-induced acute pancreatitis after induction of the disease. It also
      reduces lung injury by preventing increased pulmonary capillary permeability. In
      a double-blind, randomized, Phase II, clinical study of lexipafant in human acute
      pancreatitis, a clinical benefit was found, as indicated by a significant
      reduction in an organ failure score measured during 72 h of infusion. In
      addition, organ failure recovered in seven of 12 severe acute pancreatitis
      patients treated with lexipafant, but recovered in only two of 11 patients given
      placebo. New organ failure developed in a further two patients on placebo. The
      results of these studies indicate that lexipafant is a potential therapy for the
      treatment of human acute pancreatitis. A multicentre, Phase III, UK study in
      patients with severe acute pancreatitis is currently underway.

PMID- 8865467
TI  - Activation of human granulocyte type 1-prophospholipase A2.
AB  - Using an assay for measurement of released type 1-prophospholipase A2 (type 1
      proPLA2) propeptides (PROP assay), we have shown that human granulocytes, but not
      lymphocytes or macrophages, abundantly express this 'pancreatic' type 1-proPLA2
      zymogen. Stimulation with tumour necrosis factor-alpha (TNF-alpha) and other
      cytokines results in the immediate release from granulocytes of a mixture of free
      propeptides and type 1-proPLA2 precursor. We also found that granulocytes contain
      an approximately 29 kDa trypsin-like endogenous type 1-proPLA2 activator. PROP
      assay and TAP (trypsinogen activation peptide) assay of plasma samples accurately
      predicts the segregation of acute pancreatitis into three clearly defined
      categories of severity--mild, intermediate and severe--at the time of first
      hospital admission and over the next few hours of observation. Mild and
      intermediate pancreatitis are associated with a degree of granulocyte stimulation
      limited to the release of the unactivated type 1-proPLA2 precursor. Progression
      to severe disease is accompanied by the activation of granulocyte type 1-proPLA2,
      apparently carried to completion. This identifies the approximately 29 kDa
      endogenous activator of type 1-proPLA2 in granulocytes as a critical mediator at
      a threshold stage in acute pancreatitis, which marks the transition from
      uncomplicated pancreatitis to the potentially lethal disease. Specific inhibitors
      of this key regulatory enzyme modelled on the P3-P1 domain of the type 1-proPLA2
      activation peptide would seem to be promising candidates for a new class of
      chemotherapeutic agents.

PMID- 8865469
TI  - Mononuclear phagocyte activation and acute pancreatitis.
AB  - Severe, acute pancreatitis is commonly associated with a systemic illness which
      may result in multiple organ failure. There is evidence that an aberrant immune
      response, involving increased secretion of proinflammatory cytokines from
      activated monocytes and mononuclear phagocytes, is responsible for another
      systemic illness--septic shock. Previous studies have investigated whether there
      is a correlation between plasma cytokine levels and severity of pancreatitis.
      However, these results may not reflect mononuclear phagocyte activation. In this
      paper, monocytes (collected from patients with severe pancreatitis) were cultured
      in vitro and secreted cytokine levels measured after 24 hours by ELISA. Secretion
      of tumour necrosis factor alpha, interleukin-6 and interleukin-8 was higher in
      cells taken from patients who later developed systemic complications. There was
      no difference in the secretion of interleukin-1 beta. The mechanism by which
      mononuclear phagocytes are activated in acute pancreatitis, and the role of
      genetic predisposition, are discussed.

PMID- 8865470
TI  - Interleukins in acute pancreatitis.
AB  - Cytokines and their endogenous antagonists are released from inflammatory cells
      during acute pancreatitis, in particular its severe form. They can be found early
      in the course of the disease as is shown in animal models and in endoscopic
      retrograde cholangio-pancreatography (ERCP) induced human pancreatitis. Cytokine
      measurements can predict the course of the disease. This can, however, be
      achieved using more simple parameters, such as clinical judgement and leucocyte
      elastase. Anticytokine strategies in the treatment of severe acute pancreatitis
      should be further evaluated since some positive effects have been found in
      experimental settings. Interleukin 10 or soluble TNF alpha-receptors may be good
      candidates. Plasmapheresis seems to change cytokine-anticytokines patterns and
      this also needs to be explored in controlled trials.

PMID- 8865471
TI  - Circulating endotoxin, tumour necrosis factor-alpha, and their natural
      antagonists in the pathophysiology of acute pancreatitis.
AB  - Inflammatory mediators, such as endotoxin and tumour necrosis factor-alpha (TNF
      alpha) have been implicated in the pathogenesis of acute pancreatitis. However,
      serum levels of these mediators in patients with acute pancreatitis are often not
      detectable on hospital admission. In contrast, their circulating antagonists
      (antiendotoxin antibodies and soluble TNF-alpha receptors) are detectable in all
      patients. With increasing severity of disease, patients are more likely to
      manifest a fall in antiendotoxin levels, suggesting exposure to endotoxin.
      Similarly, there is a stepwise increase in soluble TNF-alpha receptors with
      increasing severity of disease. This suggests that the degree of TNF-alpha
      induced inflammation correlates with disease severity. The role of endotoxin, TNF
      alpha and their relevant antagonists as markers or mediators of the systemic
      complications of acute pancreatitis remains under investigation.

PMID- 8865472
TI  - Protease-antiprotease interactions and the rationale for therapeutic protease
      inhibitors.
AB  - A number of pancreatic enzymes have been suggested as the initiating factor for
      acute pancreatitis. In particular, the relationship between proteases and
      antiproteases has been examined extensively, based on the suspicion that an
      imbalance between them is the central factor in the pathogenesis of acute
      pancreatitis. Animal studies with antiproteolytic agents in models of acute
      pancreatitis have shown an improvement in outcome. However, more recently,
      prospective, randomized, multicentre trials treating human acute pancreatitis
      with antiproteolytic drugs (aprotinin, gabexate mesilate, and even fresh frozen
      plasma) have failed to show any benefit in the clinical setting. Thus,
      clinically, it seems likely that antiproteolytic therapy has no effect on the
      course of severe acute pancreatitis. Today, the mortality in severe acute
      pancreatitis is determined by septic complications due to infected pancreatic
      necroses in the late phase 2-3 weeks after the onset of the disease. Death in the
      early phase of the disease has become increasingly rare where an imbalance
      between proteases and antiproteases may be involved.

PMID- 8865473
TI  - Is screening for prostate cancer necessary in men with symptoms of benign
      prostatic hyperplasia?
AB  - In this report, we review the critical issues concerning the early detection of
      prostate cancer in patients presenting with symptoms of benign prostatic
      hyperplasia (BPH). Only with the recent introduction of serum prostate-specific
      antigen (PSA) testing and transrectal ultrasonography (TRUS)-guided biopsy has
      the question arisen to what extent the treating physician has a responsibility to
      rule out prostate cancer before recommending treatment-or watchful waiting-for
      men with clinical BPH. Uneasiness and uncertainty also result from the
      development of alternative therapies that do not provide tissue for pathological
      analysis, or alter serum PSA levels in a poorly predictable fashion. Current
      early detection strategies, in this clinical situation, pose unique problems,
      largely because of the great degree of overlap in serum PSA among men with
      localized prostate cancer and BPH. The underlying goal is to distinguish patients
      with BPH alone from those with clinically significant, but organ-confined and
      potentially curable prostate cancer. Treatment for prostate cancer may take
      precedence over BPH management strategies, while at the same time address the
      symptoms associated with coexistent clinical BPH. The issues discussed in this
      report should aid the clinician in the evaluation of patients with clinical BPH.
      Further studies are clearly needed that may ultimately enhance our ability to
      discriminate patients with clinically significant organ-confined prostate tumors
      from those with BPH alone.

PMID- 8865474
TI  - Use of prostate-specific antigen (PSA) and PSA density in the detection of stage
      T1 carcinoma of the prostate.
AB  - Serum prostate-specific antigen (PSA) has greatly enhanced our ability to detect
      carcinoma of the prostate. Yet, because of its lack of specificity for
      malignancy, approximately two thirds of the men with an elevated PSA level do not
      have prostate cancer. This problem is particularly relevant to men whose prostate
      feels normal by digital rectal examination (DRE) and appears normal by
      transrectal ultrasound (TRUS). Carcinoma of the prostate, if detected in these
      men, is staged as T1c and is usually considered to be of clinical significance.
      Attempts at refining PSA have included attempts to correct the serum level
      relative to the size of the prostate (PSA density). Although conflicting data has
      been reported in the literature, it appears when stratified for PSA ranges
      between 4 and 10 ng/mL, PSA density does not provide an advantage over PSA alone
      in cancer detection in patients with a normal DRE and TRUS.

PMID- 8865475
TI  - Evaluation of men on finasteride.
AB  - Finasteride, an orally active type II 5 alpha-reductase (5 alpha R) inhibitor,
      blocks conversion of testosterone (T) to dihydrotestosterone (DHT). The utility
      of finasteride in effectively managing benign prostatic hyperplasia has been
      documented. Use of the drug results in reduced prostate volume and serum levels.
      Patients receiving finasteride should be monitored with periodic digital-rectal
      examination (DRE) and serum PSA measurement. Patients with a sustained increase
      in serum PSA or an abnormal DRE require additional evaluation. There is no
      evidence that use of finasteride has an adverse effect on prostate cancer
      detection, if the drug's effect on serum PSA is recognized and accounted for.

PMID- 8865476
TI  - Pathological definitions and characteristics of stage T1 prostate cancer.
AB  - The American Joint Committee on Cancer (AJCC) defines T1 prostate cancers as
      clinically inapparent tumors not palpable or visible by imaging. Given the use of
      serum prostate-specific antigen (PSA), more of these incidental carcinomas are
      being detected by needle biopsy as part of a work-up for an increased PSA.
      However, the pathological characteristics and the biological potential of these
      tumors are quite variable. This chapter summarizes some of the recent literature
      describing pathobiological features of T1 tumors, their subclassification, and
      the problems encountered in diagnosing these carcinomas.

PMID- 8865477
TI  - Prostatic intraepithelial neoplasia: significance and management.
AB  - Prostatic intraepthelial neoplasia (PIN) is a putative premalignant change that
      bears a morphological similarity to prostatic cancer and shows increased
      frequency, severity, and extent in patients with prostate cancer. This article
      discusses the evidence for PIN as a premalignant lesion, reviews the morphology,
      terminology, appropriate grading system, and diagnostic significance of PIN, as
      well as describes management recommendations for further evaluation when PIN is
      diagnosed in prostate resection and biopsy specimens. Clinical management of high
      grade PIN found in transurethral resection of the prostate (TURP) or prostate
      biopsy specimens should include repeat transrectal ultrasound (TRUS) and prostate
      biopsy for early detection of prevalent coexistent prostate cancer. In cases of
      high-grade PIN, increased surveillance methods have the potential to decrease
      morbidity and mortality by early cancer diagnosis.

PMID- 8865478
TI  - Staging of incidentally detected prostate cancer: role of repeat resection,
      prostate-specific antigen, needle biopsy, and imaging.
AB  - Numerous studies have confirmed the distinct biological behavior of two subsets
      of prostate cancer diagnosed incidentally after either transurethral resection
      (TURP) or open prostatectomy for presumed benign prostatic hyperplasia (BPH).
      Focal, low-grade lesions are associated with a low risk for clinical progression
      and are designated as stage T1a or A1. These cases have traditionally been
      managed conservatively with close clinical observation. In contrast, multifocal,
      high-volume, or high-grade tumors are associated with a more aggressive clinical
      course and are designated as stage T1b or A2. Early definitive intervention is
      usually advocated for these latter patients. Therefore, accurate pathological
      assignment to either stage T1a or T1b is crucial for selection of appropriate
      management options. A variety of methods for staging patients with incidentally
      detected prostate cancer have been proposed, including detailed histological
      analysis, repeat TURP or transurethral biopsy, serial prostate-specific antigen
      (PSA) analysis, and imaging with either transrectal ultrasound (TRUS) or magnetic
      resonance (MRI) techniques. This article critically examines the clinical utility
      of these staging modalities for patients with incidentally detected prostate
      cancer.

PMID- 8865479
TI  - Can insignificant prostate cancer be predicted preoperatively in men with stage
      T1 disease?
AB  - This study reviews the pathological findings in nonpalpable prostate cancer
      detected on transurethral resection (TUR) (stages T1a and T1b) and on needle
      biopsy (stage T1c) to determine whether insignificant cancers can be predicted
      preoperatively. The majority of stage T1a cancers are insignificant and all stage
      T1b cancers are significant. Preoperative pathological parameters cannot identify
      the minority of T1a cancers that are more significant and the minority of T1b
      cancers with relatively little residual cancer. Although most nonpalpable tumors
      diagnosed by screening techniques are usually significant tumors, which would be
      treated aggressively if they were palpable, 12% to 26% of cancers removed from
      nonpalpable disease are relatively insignificant. There is conflicting data as to
      whether a combination of needle biopsy findings and PSA density measurements can
      aid in the prediction of insignificant cancers. If conservative management is
      considered, a patient should undergo repeat biopsies (including transition zone
      biopsies) to detect those more significant cancers that may have been
      undersampled. In addition, serial serum PSA measurements should be performed to
      detect whether serum PSA levels increase to a point where these tumors would be
      reclassified as significant. When planning therapy for T1 patients, the age,
      comorbidity, and treatment preferences of the patient are key factors that must
      also be taken into account.

PMID- 8865480
TI  - Does transurethral resection of the prostate compromise the radical treatment of
      prostate cancer?
AB  - Obstructive voiding symptoms are frequent complaints in men with prostate cancer.
      Some men with prostate cancer require transurethral resection of the prostate
      (TURP) for relief of these symptoms. Two central questions have been raised
      regarding whether TURP may have adverse effects on morbidity and mortality in
      patients with prostate cancer. The first question deals with potential tumor cell
      dissemination at the time of TURP, resulting increased progression and mortality
      rates. A review of the literature suggests the risk of tumor dissemination during
      a TURP is small or negligible. However, patients with prostate cancer and
      obstructive symptoms appear to have a greater likelihood of high-stage disease at
      presentation. When the pathological stage is known, progression and mortality
      outcomes are similar in TURP and non-TURP treated patients with prostate cancer.
      The second question deals with the potential that TURP increases treatment
      related morbidity of radiation therapy or radical prostatectomy. When TURP is
      required before radiation therapy, the literature suggests that delaying
      radiation 6 to 8 weeks from the time of the TURP will minimize incontinence and
      bladder neck contracture to acceptable levels. The literature also indicates that
      radical prostatectomy may be performed with no increased morbidity following a
      TURP.

PMID- 8865481
TI  - Management of stage T1a prostate cancer.
AB  - The patient with incidentally discovered prostate cancer by transurethral
      resection of the prostate (TURP) presents a difficult management problem for the
      clinician. These tumors are small and generally of low biologic potential.
      Offering aggressive treatment is not necessary in most patients; though in some
      patients, the tumor is not organ confined. Selecting that patient who may require
      tumor eradication to optimize survival requires careful analysis of known
      histological parameters identified at the time of diagnosis, an estimation of
      projected individual survival, and extensive counseling regarding options.

PMID- 8865482
TI  - Management of stage T1b (A2) and stage T1c adenocarcinoma of the prostate.
AB  - The management of stage T1b (A2) and T1c adenocarcinoma of the prostate is
      somewhat controversial. With the widespread use of serum prostate-specific
      antigen (PSA) determinations, an increasing number of these cancers are likely to
      be diagnosed. Hence, it is important to formulate a cogent management strategy
      for these patients, because a large percentage of them can be expected to have
      clinically and pathologically localized disease. Expectant observation with
      deferred treatment, radical prostatectomy, radiation therapy (external beam or
      brachytherapy), and cryosurgical ablation are all primary therapeutic options
      that have individual merit. In this review, we attempt to analyze the results of
      the various treatment options for these patients and evolve a practical approach
      towards their management.

PMID- 8865483
TI  - Imaging of bursae around the shoulder joint.
AB  - The authors present a review of the anatomy of the major bursae around the
      shoulder joint and discuss the use of the different imaging modalities which
      demonstrate their radiologic features. The calcified subacromial-subdeltoid bursa
      has a characteristic appearance on plain radiographs. When inflamed it can be
      visualized by ultrasound and magnetic resonance imaging. Calcific bursitis may
      involve the subcoracoid bursa. This bursa may mimic adhesive capsulitis of the
      shoulder or complete rotator cuff tear when injected inadvertently during
      shoulder arthrography. Less well known are three coracoclavicular ligament
      bursae. These are also subject to calcific bursitis and have a typical radiologic
      appearance.

PMID- 8865484
TI  - Tendon shift in hallux valgus: observations at MR imaging.
AB  - OBJECTIVE: This study was undertaken to demonstrate a shift in tendon alignment
      at the first metatarsophalangeal joint in patients with hallux valgus by means of
      magnetic resonance imaging. DESIGN: Ten normal feet and 20 feet with the hallux
      valgus deformity conforming to conventional clinical and radiographic criteria
      were prospectively studied using magnetic resonance imaging. Correlation was made
      between tendon position at the first metatarsophalangeal joint and the severity
      of the hallux valgus deformity. RESULTS: There is a significant shift in tendon
      position at the first metatarsophalangeal joint of patients with hallux valgus.
      The insertion of the abductor hallucis tendon is markedly plantarward and the
      flexor and extensor tendons bowstring at the first metatarsophalangeal joint
      compared with patients without the deformity. The severity of the tendon shift
      correlates with the hallux valgus angle and clinical severity of the hallux
      valgus deformity in each case. CONCLUSION: Patients with hallux valgus have a
      significant tendon shift at the first metatarsophalangeal joint which appears to
      contribute to development of the deformity.

PMID- 8865485
TI  - Absence or interruption of the supra-acetabular line: a subtle plain film
      indicator of hip pathology.
AB  - OBJECTIVE: To show that absence or interruption of the supra-acetabular line is a
      subtle plain film indicator of pathology in the acetabulum. DESIGN: Nineteen hips
      from 17 patients with known disease processes involving the acetabulum as
      demonstrated by subsequent magnetic resonance imaging, bone scan or plain film
      follow-up were evaluated with antero-posterior (AP) plain films of the pelvis.
      Three additional cases were diagnosed prospectively using interruption of the
      supra-acetabular line as the criterion for inclusion. Fifty AP plain films of the
      pelvis in patients without hip pain were examined prospectively to determine
      normal imaging criteria. RESULTS AND CONCLUSIONS: The normal supra-acetabular
      line measures 2-3 mm in thickness superiorly and is a thin sclerotic line in the
      medial aspect. In all 22 hips (with pathology) in this series, the line was
      interrupted or absent. Loss or interruption of the supra-acetabular line may thus
      be a subtle pain film indicator of a disease process involving the acetabulum.
      This plain film sign has not previously been reported.

PMID- 8865486
TI  - Spinal osteoblastoma: relationship between paravertebral muscle abnormalities and
      scoliosis.
AB  - OBJECTIVE: To illustrate the variety of paravertebral muscle abnormalities as
      seen on computed tomography (CT) or magnetic resonance imaging (MRI) in
      association with spinal osteoblastomas and correlate the findings with the
      presence of scoliosis. DESIGN: In a retrospective study the clinical notes, plain
      radiographic, CT and/or MRI features were reviewed for the presence of scoliosis
      and paravertebral muscle abnormality (either inflammation or atrophy). PATIENTS:
      Twelve patients (7 male, 5 female) with a mean age of 17 years were studied.
      Three lesions occurred in the cervical spine, five in the thoracic spine and four
      in the lumbar spine. RESULTS AND CONCLUSIONS: Nine patients had scoliosis. All
      patients with a thoracic or lumbar lesion and scoliosis (n = 8) had an associated
      abnormality of the paravertebral muscles (usually atrophy with fatty
      replacement). One patient with a lumbar lesion and no scoliosis had normal
      paravertebral muscles. One patient with a cervical lesion had thoracic scoliosis
      but no muscle abnormality in the cervical region, while two patients with
      cervical lesions and no scoliosis showed muscle abnormalities. The results
      support the clinical hypothesis that scoliosis in patients with spinal
      osteoblastoma is due to paravertebral muscle spasm, although this would not
      appear to be the case for cervical lesions.

PMID- 8865487
TI  - MR characterization of post-irradiation soft tissue edema.
AB  - OBJECTIVE: Radiation therapy is often used to treat bone und soft tissue
      neoplasms, and commonly results in soft tissue edema in the radiation field.
      However, the time course, distribution and degree of this edema have not been
      well characterized. Our study was carried out to better define these features of
      the edema seen following neutron and photon radiation therapy. DESIGN AND
      PATIENTS: Two hundred and twenty-six patients underwent radiation therapy as part
      of combined modality management for musculoskeletal sarcomas between 1985 and
      1993. Of these, 15 had surgical resection of their neoplasm, had no clinical
      evidence of recurrent disease, and had adequate MR follow-up that allowed
      sequential assessment of soft tissue following irradiation. Ten patients received
      photons with an average dose of 52.8 Gy. Five patients received neutrons with an
      average dose of 17.3 nGy. Sequential MR follow-up was available in these patients
      for an average of 22.8 months following radiation therapy. On each of the serial
      MR imaging studies, subcutaneous fat, muscle, and the intramuscular septa/fascial
      planes were graded subjectively as to size and signal intensity. RESULTS: In
      general, soft tissue signal intensity in the radiation field initially increased
      over time, peaking at about 6 months for neutron-treated patients and at about 12
      18 months for photon-treated patients. Signal intensity then decreased slowly
      over time. However, at the end of the follow-up period, signal intensity remained
      elevated for most patients in both groups. Signal intensity in a particular
      tissue was greater and tended to persist longer on STIR sequences than on T2
      weighted sequences. Survival analysis of signal intensity demonstrated much
      longer edema survival times for neutron-treated patients than for photon-treated
      patients. Signal intensity increase in the intramuscular septa persisted for much
      longer than for fat or muscle. A mild increase in size was noted in the
      subcutaneous fat and intramuscular septa. Muscle, on the other hand, showed a
      decrease in size following treatment. This was mild for the photon-treated group
      and more marked for the neutron-treated group. CONCLUSIONS: There is a relatively
      wide variation in the duration and degree of post-irradiation edema in soft
      tissues. This edema seems to persist longer in the intramuscular septa than in
      fat or muscle. Although the duration of follow-up was limited, our study suggests
      that this edema resolves in roughly half the photon-treated patients within 2-3
      years post-treatment and in less than 20% of neutron-treated patients by 3-4
      years post-treatment. Muscle atrophy was seen in both photon- and neutron-treated
      patients, but was more severe in the neutron-treated group.

PMID- 8865488
TI  - Precision of sonographic measurement of articular cartilage: inter- and
      intraobserver analysis.
AB  - OBJECTIVE: To establish the precision of sonographic measurement of the thickness
      of the articular cartilage of the hip and knee in children. DESIGN: The precision
      was assessed by evaluating the intra- and interobserver variations in sonographic
      measurements. PATIENTS: A total of 65 healthy children were in the study. The
      articular cartilage of the right hip and knee of 40 subjects (mean age 10.3
      years, range 4-16.9 years) was evaluated in masked fashion by two observers to
      assess the interobserver variability. The articular cartilage of the right hip
      and knee of 25 children (mean age 10.4 years, range 6.2-15.5 years) was examined
      twice by the same observer to assess the intraobserver variability. RESULTS AND
      CONCLUSIONS: Discrepancies between repeated measurements were expressed as data
      differences. The "limits of agreement" of data differences, i.e. the mean +2 SD
      and the mean -2 SD, ranged from -0.26 to +0.22 mm and from -0.56 to +0.48 mm for
      the interobserver analysis of the femoral head cartilage (FHC) and femoral
      condylar cartilage (FCC), respectively. The "limits of agreement" for the
      intraobserver analysis ranged from -0.16 to +0.15 mm and from -0.51 to +0.41 mm
      for the FHC and the FCC, respectively. The overall precision of the sonographic
      measurements was satisfactory. When used for determination of skeletal age,
      sonographic assessment of FHC thickness resulted in under/overestimation of
      skeletal age by about 7.5 months. In conclusion, sonographic measurement of
      articular cartilage is precise enough to be used in clinical practice.

PMID- 8865489
TI  - Rotator cuff calcifications: treatment with ultrasound-guided percutaneous needle
      aspiration and lavage.
AB  - OBJECTIVE: To analyze the results of ultrasound (US)-guided needle puncture,
      aspiration and lavage in the treatment of symptomatic calcific tendinitis of the
      rotator cuff. DESIGN AND PATIENTS: Atraumatic pain in 61 shoulders of 58 patients
      was resistant to conservative therapy. The average age of the treated patients
      was 42 years (range 26-49 years), follow-up was 12 months, and the mean diameter
      of the calcifications was 1.6 cm (range 1.1-2.9 cm). With US guidance and local
      anesthesia, two needles were placed within each calcification. The calcification
      was punctured 10-15 times and saline solution injected and aspirated using the
      needles until the aspirate was free of calcific particles. RESULTS AND
      CONCLUSIONS: Based on radiographs at 1 year follow-up. 74% (45 of 61) of the
      calcifications decreased, including 28% (17 of 61) which disappeared totally, and
      26% (16 of 61) were unchanged. Calcifications with a faint or absent shadow on US
      proved to be nearly liquid (slurry calcification in 93% (14 of 15) of cases and
      could be aspirated. Clinical results were excellent in 74% (45 of 61), moderate
      in 16% (10 of 61) and poor in 10% (6 of 61) of cases. US offers technical
      advantages over fluoroscopy, and the typical US image of a slurry calcification
      helps to select the most suitable patients for aspiration treatment. The results
      are comparable with those using fluoroscopic guidance.

PMID- 8865490
TI  - Rotator cuff strain: a post-traumatic mimicker of tendonitis on MRI.
AB  - OBJECTIVE: To determine whether there is a subset of young patients (< 35 years)
      with acute, post-traumatic insults to the rotator cuff which mimic the early
      stages of impingement. DESIGN AND PATIENTS: One hundred and ninety-seven
      consecutive shoulder MR images were retrospectively reviewed, and the results of
      83 clinically correlated. Two observers independently evaluated the location of
      intra-tendon signal and adjacent bone marrow abnormalities on T1- and T2-weighted
      images. These findings were correlated with age, history of trauma, and surgical
      or clinical follow-ups. RESULTS: Patients younger than 35 years had signal
      intensity that was more localized in atypical locations (posterior aspect of the
      supraspinatus tendon), more commonly associated with marrow abnormalities
      (presumed bone bruise), and more often associated with trauma. Younger patients
      also were less likely to require surgery, especially if they showed bone bruises.
      This differentiated them from older patients (> 45 years), who demonstrated more
      widespread signal within the tendon, rare bone bruises, and more frequent
      surgery. CONCLUSIONS: Localized tendon signal in atypical locations of the
      supraspinatus tendon, particularly when associated with bone bruise and young
      age, suggests the possibility of a post-traumatic strain.

PMID- 8865491
TI  - Hill-Sachs lesion: sonographic detection.
AB  - OBJECTIVE: To determine the value of ultrasonography (US) in the detection of
      Hill-Sachs lesion of the humerus in comparison with double-contrast computed
      tomographic arthrography (CTA) and with arthroscopy. DESIGN AND PATIENTS: US and
      CTA were performed on 92 patients, 86 of whom subsequently underwent arthroscopy.
      The findings of US, CTA and arthroscopy in these 86 patients in the diagnosis of
      Hill-Sachs lesion were analyzed. RESULTS AND CONCLUSIONS: In the detection of
      Hill-Sachs lesion US showed a sensitivity of 91% (21 of 23), a specificity of 95%
      (60 of 63) and an accuracy of 94% (81 of 86) when compared with CTA, and a
      sensitivity of 94% (18 of 19), specificity of 91% (61 of 67) and accuracy of 91%
      (79 of 86) when compared with arthroscopy. In only 2% (2 of 86) of patients was
      there reduced visualization because of restriction of movement. Hill-Sachs lesion
      and its relationship to the humeral head can be reliably diagnosed with US.

PMID- 8865492
TI  - Positioning aid solves the reproducibility problem during oblique hand
      radiography: a cheap and effective solution.
AB  - OBJECTIVE: A commercially available positioning device was evaluated to assess
      whether standardized positioning of hand radiographs for the pronated oblique
      view was facilitated. DESIGN AND SUBJECTS: One hundred hands of volunteers were
      radiographed in postero-anterior, anteroposterior and pronated oblique
      projections, with and without use of the positioning device, and with and without
      application of a plaster cast. RESULTS: The variation in pronation angle in the
      uncovered hand was 6 degrees with, and 24 degrees without the positioning device.
      Use of the device diminished intra- and inter-positioning variation by 14 degrees
      and 18 degrees respectively. A plaster cast led to a variation of up to 26
      degrees, despite use of the device. CONCLUSIONS: Use of the positioning device
      improved consistency for the pronated oblique radiograph. There was no
      improvement with a cast on the forearm.

PMID- 8865493
TI  - Tuberculous tenosynovitis of the wrist: MRI findings in three patients.
AB  - We report recent MRI findings in patients with tuberculous tenosynovitis of the
      wrist. Marked synovial thickening around the flexor tendons and fluid in the
      tendon sheath were clearly shown on MRI. Post-contrast study was useful in
      distinguishing the thick tenosynovium from the surrounding structures and fluid
      in the tendon sheath. The well-enhanced tenosynovium was also seen in the carpal
      tunnel in all cases. On the basis of these findings, we could easily distinguish
      tenosynovitis from other soft-tissue-mass lesions, such as tumors or infected
      ganglia. Tuberculous tenosynovitis is often not diagnosed early, and its
      differentiation from soft tissue tumors may be clinically difficult. MRI,
      particularly post-contrast study, is useful for early diagnosis of, and planning
      treatment for, tuberculous tenosynovitis.

PMID- 8865494
TI  - Myxolipoma mimicking a cystic tumor.

PMID- 8865495
TI  - Tropical pyomyositis: imaging findings and a review of the literature.
AB  - Tropical pyomyositis is a rare cause of multiple abscesses of skeletal muscle.
      The entity is rare in temperate climates and, as its name suggests, is more
      common in areas such as the tropics and South Pacific. Staphylococcus aureus is
      the most common cause of infection. Therapy is aggressive, with surgical
      debridement and drainage followed by antibiotics. We report an unusual case of
      tropical myositis which simulated tumor recurrence in a patient without the
      typical risk factors associated with tropical pyomyositis.

PMID- 8865496
TI  - Avulsion fracture of the anterior inferior iliac spine with abundant reactive
      ossification in the soft tissue.
AB  - Patients who have sustained an avulsion fracture and present clinically during
      the healing phase of the injury may manifest a mass that clinically and
      radiographically mimics a malignant neoplasm. A 15-year-old male soccer
      goalkeeper presented with a large ossified mass in the soft tissues overlying the
      right hip 6 months after experiencing a popping sensation in his hip joint during
      a game. Although an osteosarcoma was suspected clinically and radiographically, a
      Tru-Cut needle biopsy of the lesion revealed reactive bone formation. Correlation
      of the clinical, radiographic, and pathologic findings indicated an avulsion
      fracture of the anterior inferior iliac spine with abundant reactive ossification
      in the soft tissues. The healing phase of an avulsion fracture may clinically and
      radiographically be mistaken for neoplasia. In such cases, a Tru-Cut needle
      biopsy may reveal the reactive nature of the process.

PMID- 8865497
TI  - Adenocarcinoma of the lung metastatic to the psoas muscle.
AB  - Hematogenous metastasis to the psoas muscle is rare, and the resulting clinical
      symptoms may mimic psoas abscess or hemorrhage. When the clinical history is not
      specific, CT is important in documenting the presence of a psoas mass and
      providing biopsy guidance for histologic diagnosis. Only three previously
      reported cases have been related to a primary carcinoma of the lung.

PMID- 8865498
TI  - Intraosseous ganglion of the patella.
AB  - Osteolytic cystic lesions of the patella are rare lesions. A review of the
      literature revealed only one previously reported example. The pathogenesis and
      radiological and pathological features of intraosseous ganglion cysts are
      discussed. In addition, the differential diagnosis of lytic patellar lesions is
      discussed.

PMID- 8865499
TI  - Chondroid lipoma: MRI appearances with clinical and histologic correlation.
AB  - Chondroid lipoma is a recently described benign tumor of adipose origin which,
      pathologically, mimics myxoid liposarcoma and myxoid chondrosarcoma. This tumor
      typically presents as a well-defined mass in the superficial tissues of the
      extremities. In this report, we present the magnetic resonance imaging (MRI)
      appearances of a pathologically proven chondroid lipoma. To our knowledge, this
      is the first report of any imaging findings associated with this tumor.

PMID- 8865500
TI  - Post-radiation osteosarcoma of the scapula.
AB  - Osteosarcomas arising in irradiated tissues are uncommon but important
      complications of radiotherapy. Radiation-induced osteosarcomas generally occur 3
      30 years after exposure and are most common after radiotherapy for cervical or
      breast carcinoma. These tumors are usually rapidly growing, extremely painful,
      and histologically high grade. In this paper, we report two cases of high-grade
      post-radiation osteosarcoma of the scapula. Despite being almost identical
      radiologically and pathologically, one case had a typical clinical presentation
      whereas the second case had two unusual features, being non-painful and arising
      in a field initially irradiated for bronchogenic carcinoma.

PMID- 8865501
TI  - The consequences of a week of insomnia.
AB  - A yoked control study used sleep recordings from 10 insomniacs to produce similar
      sleep patterns in a group of matched normal sleepers for 7 nights to determine if
      specific electroencephalographic (EEG) sleep patterns were responsible for the
      secondary insomnia symptoms reported by the insomniacs. Specifically, it was
      found that insomniacs display increased tension/confusion, decreased vigor,
      personality disturbance, subjective over-estimation of poor sleep, increased body
      temperature, increased 24-hour whole body metabolic rate, and increased multiple
      sleep latency test (MSLT) values. Normal sleepers given the nocturnal EEG
      parameters of insomniacs displayed decreased tension, decreased vigor, decreased
      body temperature, and decreased MSLT values. The spectrum of changes seen in the
      normal sleepers given an insomniac sleep pattern was characteristic of mild
      partial sleep deprivation and not consistent with symptoms found in patients with
      primary insomnia. It was concluded that the secondary symptoms reported by
      patients with primary insomnia are probably not related to their poor sleep per
      se. Data from previous studies that varied physiological arousal were used to
      support the contention that the secondary symptoms of insomnia, including poor
      sleep, occur secondary to central nervous system hyperarousal.

PMID- 8865502
TI  - Historical change in the report of daytime fatigue.
AB  - Population-based data suggesting that contemporary society does not value sleep
      are difficult to obtain. In this report, historical change in item endorsements
      relevant for disturbed sleep and daytime fatigue from the Minnesota Multiphasic
      Personality Inventory (MMPI) generated from normative, upper Midwestern adult
      populations was analyzed. Response rates from the 1930s and 1980 were compared.
      The data indicated that, relative to individuals in the post-Great Depression/pre
      World War II era, contemporary men were more likely to report fatigue and
      tiredness, although they were no more likely to report disturbed nocturnal sleep.
      The results are compatible with the voluntary curtailment of sleep typical in
      modern society described in the report of the National Commission on Sleep
      Disorders Research.

PMID- 8865503
TI  - Does upper airway muscle injury trigger a vicious cycle in obstructive sleep
      apnea? A hypothesis.
AB  - Recent studies have indicated that the level of neural activation of upper airway
      dilator muscles is abnormally elevated in patients with obstructive sleep apnea
      (OSA). This is presumed to represent an adaptive mechanism that partially
      compensates for the anatomically small upper airway found in individuals with
      OSA. We have reviewed evidence that pharyngeal dilator muscles undergo secondary
      changes in structure as a direct consequence of their increased activity level in
      OSA. These alterations have the potential to be both beneficial and harmful with
      respect to the maintenance of upper airway patency. We propose a model outlining
      the possible role of activity-induced upper airway muscle remodeling and injury
      in the pathogenesis of OSA, and discuss potential implications for treatment of
      the disease.

PMID- 8865504
TI  - Respiratory responses to tracheobronchial stimulation during sleep and
      wakefulness in the adult cat.
AB  - The response to tracheal stimulation (50 microliters of tap water) during
      wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM)
      sleep was investigated in adult cats. In wakefulness, repetitive coughing
      occurred on 80% of the trials. In NREM and REM sleep, the most frequent response
      (approximately 69% and 58% of the trials, respectively) was arousal, followed by
      coughing. Apneas occurred following the stimulus and before arousal in 11% and
      24% of the trials in NREM and REM sleep, respectively. In NREM sleep, the
      tracheal stimulus sometimes evoked expiratory efforts following a normal
      inspiratory effort (11% of the trials). These were much weaker than the
      expiratory efforts during coughing in wakefulness. In REM sleep, stimulation in
      11% of the trials elicited increased inspiratory efforts. Although these may have
      been diminutive preparatory inspirations for coughing, they were much smaller
      than preparatory inspirations associated with coughing in wakefulness, and they
      were never followed by active expiratory efforts. Arousal from either NREM or REM
      sleep in response to tracheal stimulation was sometimes associated with an
      augmented breath. This response, which is common upon spontaneous arousal, may
      lead to deeper aspiration of the tracheal fluid. We conclude that in cats
      coughing requires wakefulness and that airway stimuli in sleep cause a variety of
      respiratory responses, some of which may be maladaptive.

PMID- 8865505
TI  - Sleep-related breathing disorders in patients with multiple system atrophy and
      vocal fold palsy.
AB  - We performed sleep studies in eight patients with multiple system atrophy (MSA)
      and three patients with peripheral bilateral vocal fold palsy (PBVFP) and
      investigated stenosis of the upper airway tract during sleep in MSA patients with
      vocal fold palsy. Among the eight MSA patients in this study, five had definite
      glottic snoring and two others were suspected of having glottic snoring. Of the
      PBVFP patients, two had glottic snoring. Three of 11 patients died, and two of
      the three deaths occurred during sleep. Glottic snoring indicated a high degree
      of negative esophageal pressure. High negative esophageal pressure demonstrates
      severe narrowing of the upper airway tract. Therefore, glottic snoring should be
      considered a risk factor for sudden death in sleep. Repeated laryngoscopic
      examination is useful in evaluating the progressive process of vocal fold palsy
      while awake, but this examination performed only while awake is not enough to
      evaluate narrowing of the upper airway during sleep. Sleep studies that include
      the measurement of esophageal pressure can be very useful in evaluating the
      severity of narrowing in the upper airway tract. It is suspected that sudden
      nocturnal death in MSA patients is caused not only by abnormal respiration
      resulting from impairment of the respiratory center, but also by glottic
      obstruction caused by sputum or by edema of the vocal folds. We recommend
      treatment of respiratory disorders when loud laryngeal snoring occurs in patients
      with MSA, even if they do not complain of dyspnea while awake.

PMID- 8865506
TI  - Nocturnal polysomnography with and without continuous pharyngeal and esophageal
      pressure measurements.
AB  - PSG with simultaneous pharyngeal and esophageal pressure measurements of the
      upper airway may interfere with sleep architecture and cause a bias. The aim of
      this study was to evaluate the degree of disturbance to sleep caused by inclusion
      of pressure measurements of the airway, and whether this would reduce the
      validity of the PSG. Thirty-two consecutive patients referred for PSG for
      possible obstructive sleep apnea syndrome (OSAS) were included. For pressure
      recordings, a 6-F silicone tube, 1.9 mm in diameter, containing six pressure
      transducers, was introduced through one nostril into the pharynx and esophagus.
      Each patient had two nocturnal PSGs, one of which included airway pressure
      measurements. There were no statistically significant differences between PSGs
      performed with and without simultaneous pressure recordings for the following
      sleep quality parameters: total sleep time, number of sleep-stage shifts, sleep
      efficiency, arousal during sleep (= intrasleep wakefulness), percent REM sleep,
      and number of microarousals. We did not find any statistically significant
      differences for respiratory parameters such as type, duration, and index of
      different respiratory events and snoring. However, there was a slight tendency
      for reduced sleep quality and oxygen saturation when pressure measurements were
      included. The only significant change seen was in the duration of non-REM sleep
      with oxygen saturation below 90%. The multisensor airway pressure probe
      demonstrated that proximal obstructions were more common than distal
      obstructions, and obstruction in one or two segments was far more frequent than
      obstruction in more than two.

PMID- 8865507
TI  - Computerized adjustable versus fixed NCPAP treatment of obstructive sleep apnea.
AB  - An automated positive airway pressure device that monitors respiratory patterns
      and provides dynamic, real-time, relational pressure has been developed for the
      treatment of obstructive sleep apnea (OSA). The purpose of this study was to
      compare self-adjusting pressure to classical nasal continuous positive airway
      pressure (NCPAP). Subjects were newly diagnosed patients with a minimum
      respiratory disturbance index (RDI) of 15 episodes per hour who had undergone
      NCPAP titration and been using classical NCPAP at home on a nightly basis for at
      least 2 weeks. Patients then underwent repeat standard polysomnographic (PSG)
      evaluations for 2 nights using a self-adjusting pressure mode and a standard
      NCPAP mode randomly assigned in a single-blind crossover fashion. Eight males and
      four females (n = 12), aged 48.4 +/- 12.2 years [mean +/- and standard deviation
      (SD)], completed the study. During initial diagnostic PSG, the RDI was 57.3 +/-
      30.8 episodes per hour. The RDI and minimum oxygen saturation for both treatment
      nights were significantly improved from those of the diagnostic PSGs (p < 0.001).
      The subjects spent 63.1 +/- 34.2% of total sleep time below prescribed pressure
      while on automatic pressure Percent of total sleep time in stage 3/4 sleep was
      significantly higher during self-adjusting pressure, at 8.6 +/- 7.5%, compared to
      standard NCPAP, at 4.6 +/- 6.0% (p < 0.05). Computerized adjustable nasal
      positive airway pressure effectively controls OSA, fluidly providing the minimal
      pressure necessary to control respiratory events without causing sleep
      disruption.

PMID- 8865508
TI  - Treatment of obstructive sleep apnea with a self-titrating continuous positive
      airway pressure (CPAP) system.
AB  - Conventional manually adjusted continuous positive airway pressure (CPAP) is an
      effective therapy for sleep-disordered breathing. We prospectively investigated
      the efficacy of a self-titrating nasal CPAP system in the acute treatment of
      obstructive sleep apnea (OSA) syndrome. Twenty patients with moderately severe
      OSA [apnea hypopnea index (AHI) > 15/hour] were enrolled in a randomized,
      controlled, prospective clinical trial. An initial diagnostic sleep study was
      performed, followed by randomization to a manually adjusted CPAP titration on one
      night and self titrating CPAP on the other night. On the conventional CPAP night,
      the CPAP was manually adjusted until abolition of all apneas and
      electroencephalographic (EEG) arousals, whereas the self-titrating CPAP was set
      in automatic mode at lights out. The self-titrating CPAP system utilized an
      algorithm based on airway vibration patterns to detect airway stability. The AHI
      decreased from 50.8 +/- 28.8/hour [mean +/- standard deviation (SD)] at baseline
      to 3.8 +/- 3.1/hour (p < 0.005) during manually adjusted and 6.1 +/- 5.3/hour (p
      < 0.005) during self-titrating CPAP. The arousal index (Ar-I) decreased from 34.1
      +/- 23.1/hour (baseline) to 11.2 +/- 5.0/hour on manual adjustment (p < 0.005)
      and 11.3 +/- 0.3/hour on self titration (p < 0.005), whereas total sleep time was
      unchanged. No significant differences in any measure of oxygenation or sleep
      architecture were observed between the manually adjusted and self-titrating CPAP
      nights except that the lowest arterial oxygen saturation (SaO2) was higher with
      manual titration (84.4 +/- 4.2% vs. 79.9 +/- 9.7%, p < 0.05). The maximum
      pressure required for abolition of apneas and arousals was significantly lower (p
      < 0.05) during the self-titrating study (10.1 +/- 3.8 cmH2O) as compared to
      manually adjusted CPAP (12.3 +/- 3.9 cmH2O). Failure to increase pressure and
      failure to maintain minimum pressure occurred in 7 of the 20 subjects during the
      self-titrating study. This required manual resetting of the system in five
      subjects, but the system self-corrected in two subjects. An unsupervised study
      would have resulted in undertreatment of OSA. Based on a single-night laboratory
      study, self-titrating CPAP was well tolerated and improved OSA and sleep
      architecture comparable to manually adjusted CPAP. The future modifications of
      this prototype will require further research to assess its efficacy and safety in
      the laboratory and home environments before its recommendation for general long
      term use.

PMID- 8865509
TI  - A laboratory validation study of the diagnostic mode of the Autoset system for
      sleep-related respiratory disorders.
AB  - We performed a validation study of the diagnostic mode of the Autoset system
      (ResMed, Australia) on a group of 44 snorers (10 women). We compared the result
      of the Autoset's automatic analysis of nasal airflow (using nasal prongs) to
      those of an in-laboratory polysomnographic study with a Fleisch facemask
      pneumotachograph. For the first 29 patients, the Autoset software was set to
      recognize only apneas; for the remaining 15, the software was modified to
      recognize both apneas and hypopneas. Relative to polysomnography, the Autoset
      overestimated the number of apneas. Oral breathing or displacement of the nasal
      prongs partially explained these differences. A significant correlation was found
      between the apnea indices (AI) assessed by the two methods (r = 0.98). For an AI
      of 20/hour the Autoset was 100% sensitive and 88% specific. The Autoset
      significantly underestimated the number of hypopneas compared to the
      polysomnograph with pneumotachograph (62.9 +/- 4.7 vs. 85.5 +/- 73.1, P = 0.04),
      although for an apnea-hypopnea index of 20, Autoset was 100% sensitive and 88%
      specific. The lack of linearity of Autoset's volume evaluation at low volumes
      could explain most of the differences. Our results indicate that the Autoset
      system, in its diagnostic mode, is a useful tool for identifying patients with
      significant obstructive sleep apnea syndrome. The system is less useful in
      patients with mild to moderate sleep disordered breathing, where it may give
      erroneous results.

PMID- 8865510
TI  - Is snoring dangerous to your health?
AB  - The purpose of this commentary is to review the evidence linking simple snoring
      with hypertension and cardiovascular and cerebrovascular disease. This has been a
      topic of numerous investigations with seemingly divergent results, mainly because
      of the differences in methodology employed in various studies, such as inclusion
      of confounding factors, type of population examined, methods of measurements and
      analysis, etc. Nevertheless, despite these limitations, a review of 19 studies
      examining the association between snoring and hypertension clearly shows that in
      the majority of them (14 studies) snoring was not found to be an independent risk
      factor. An association between snoring and cardiovascular and cerebrovascular
      disease is somewhat more difficult to assess. Analysis of 15 recent studies
      dealing with this issue shows that 9 of them concluded that snoring is a risk
      factor for vascular disease, whereas 6 studies reached the opposite conclusion.
      However, a detailed review of the studies showing positive association between
      snoring and vascular disease indicates that in some of them unsuspected sleep
      apnea may have accounted for this increased risk. In addition, these studies
      exhibit a number of inconsistencies that raise doubts as to the true validity of
      association between snoring and vascular disease. Finally, it does not seem
      biologically plausible that snoring should be a risk factor for cardiovascular
      and cerebrovascular disease without also being a risk factor for hypertension.
      Consequently, based on the available information, one cannot conclude that
      snoring is an independent risk factor for such adverse vascular complications as
      hypertension and cardiovascular and cerebrovascular disease.

PMID- 8865511
TI  - Bibliography of recent literature in sleep research.

PMID- 8865512
TI  - Childhood sex abuse in women with chronic intractable back pain.
AB  - This study explores the relationship between chronic intractable pain and
      histories of childhood sexual abuse in 112 women sampled from a large university
      campus health center. Fifty-nine (59) women with chronic back pain were sampled
      and compared with 53 control subjects obtained simultaneously from the same
      clinical population. Results noted that women with chronic intractable back pain
      had a significantly higher percentage of childhood sexual abuse experiences than
      controls. A new chronic back pain checklist was used.

PMID- 8865513
TI  - The relationship between therapeutic termination and job satisfaction among
      medical social workers.
AB  - This article reports the results of a 1993 study of 144 social workers and other
      health professionals (who perform discharge planning functions) in short-term
      medical treatment settings. Due to numerous unplanned therapeutic terminations
      common in these facilities, an overall correlation between therapeutic
      termination issues and worker job satisfaction was preformed. A positive
      relationship between these two variables was found and the specific factors which
      constitute these variables were further explored. The results are discussed in
      relation to the potential implications this may have regarding overall job
      satisfaction for medical social workers. Recommendations for addressing these
      factors are suggested.

PMID- 8865514
TI  - Children of Holocaust survivors: separation obstacles, attachments, and anxiety.
AB  - This article will discuss a research study conducted on the transmission of
      Holocaust trauma to children of survivors. The study examines and focuses on the
      effects Holocaust survivor parents have on their children focusing on three
      variables: separation obstacles, the ability to form substantial intimate
      relationships, and anxiety. Most Holocaust survivor parents perceive separation
      in a disapproving way and therefore it is often interpreted and handled
      differently in survivor families.

PMID- 8865515
TI  - Alcohol treatment: measurement of effectiveness by global outcome.
AB  - Traditional methods of data analysis in alcohol studies focus only on alcohol
      consumption as dependent variables rather than considering a global, person-in
      environment perspective. The purpose of this study was to evaluate treatment
      outcome in a clinical trial using dimensions of life functioning in addition to
      quantity-frequency measures of alcohol use. Subjects were male veterans suffering
      from high levels of anxiety in addition to alcohol dependence who were randomly
      assigned to treatment with a placebo or buspirone. Results show that global
      outcome measures did not reveal differences from standard treatment outcome
      measures in this study. All of those subjects who were drinking heavily, and most
      of those drinking moderately, were experiencing life problems. However, studies
      with other designs and with larger sample sizes are needed.

PMID- 8865516
TI  - Challenges to identifying and treating women with depression in rural primary
      care.
AB  - Many women seeking help from rural primary care providers are experiencing major
      or other types of depression. Women typically do not discuss their depression
      with their primary care providers although those who did reported finding it very
      helpful. Feeling understood and advice were particularly viewed as helpful. Major
      barriers to discussing depression with primary care providers include stigma
      about depression, lack of time, and perceptions that the primary care providers
      were not interested in these concerns. Depressed women tend to seek help for
      certain somatic problems, especially headaches, backaches, muscle pains, sleep
      problems, feeling tired, and abdominal pains.

PMID- 8865517
TI  - Thrombolytic therapy in pediatric patients: a comprehensive review of the
      literature.

PMID- 8865518
TI  - Genetic diagnosis of dysplasminogenemia: detection of an Ala601-Thr mutation in
      118 out of 125 families and identification of a new Asp676-Asn mutation.
AB  - Dysplasminogenemia (plasminogen abnormality) is frequently found in association
      with thrombosis. Two types of mutation, Ala601-Thr and Val355-Phe, have already
      been identified; the precise genetic defects of most of these patients, however,
      remain unknown. In this study, we examined the genetic DNAs of two unrelated
      cases by single-strand conformational polymorphism and nucleotide sequencing
      analysis. A new mutation, designated as Asp676-Asn, has been identified in these
      cases. This mutation leads to the loss of a negatively-charged residue and the
      creation of a potential carbohydrate attachment site, which may impair the
      enzymatic properties of plasminogen. As many as 158 individuals with
      dysplasminogenemia were analyzed by a combination of in vitro amplification and
      restriction digestion. Among 125 unrelated families, the Ala601-Thr mutation
      accounted for about 94% of cases. The Val355-Phe mutation was found in four
      unrelated families, indicating that it is a recurring mutation and is not very
      rare.

PMID- 8865519
TI  - New mutations causing the premature termination of translation in the A subunit
      gene of coagulation factor XIII.
AB  - The amplification of factor XIII A subunit gene exons and heteroduplex analysis
      has been used to identify two new mutations that cause severe factor XIII
      deficiency. One mutation in a family of French origin results from a 4 bp
      deletion and leads to a premature termination of translation. The other mutation
      occurred in a Turkish family and results from a C-->T transition that inserts a
      premature translation stop signal at codon 400. Both mutations alter restriction
      enzyme sites and can be readily detected in amplified exon DNA for genetic
      counselling or prenatal diagnosis. The new mutations reflect the extensive
      molecular heterogeneity of factor XIII deficiency.

PMID- 8865520
TI  - Two mutations in exon XII of the protein S alpha gene in four thrombophilic
      families resulting in premature stop codons and depressed levels of mutated mRNA.
AB  - Sixteen Danish unrelated thrombophilic families with plasma protein S deficiency
      of type 1 (or III) are currently under investigation in our laboratory for
      defects in the protein S alpha gene. The present paper describes a part of this
      work, which deals with the identification and phenotypical presentation of two
      unique mutations in exon XII of the protein S alpha gene in four of these
      families. The mutations were identified by SSCP screening followed by nucleotide
      sequence analysis or by direct nucleotide sequence analysis. The mutation found
      in one family (D) is a novel deletion of an A in either the codon for Gly448
      (GGA) or Ile449 (ATI) resulting in a frameshift and a premature stop codon at
      position 454. The other mutation shared by three families (F, G and J) is a
      previously reported C-->T transition within a hypermutable CG dinucleotide
      sequence converting Arg410 (CGA) to Stop (TGA). All affected individuals are
      heterozygotes for their mutation and in each family the protein S genotype, the
      plasma protein S phenotype (not shown for Family J) and the clinical phenotype
      cosegregate. The two mutations can fully explain the abnormal protein S phenotype
      since premature stop codons are known to disrupt gene function of the mutated
      allele. Analysis of protein S mRNA from platelets showed that both mutations
      result in a marked reduction in the amount of protein S mRNA from the mutated
      alleles indicating that the mutations exert their deleterious effects on gene
      expression at the transcriptional level. The Arg410-->Stop mutation in Families
      F, G and J is in all instances linked to a G at the site of a common neutral
      dimorphism in the codon for Pro626 (CCA/G) in exon XV. This indicates that the
      mutation in these families could have arisen in a common ancestor. The Arg410
      (CGA)-->Stop (TGA) mutation is also seen in exon XII of the normal protein S
      alpha gene. This gives rise to the speculation as to whether the mutation in the
      protein S alpha gene is the result of an interaction with the protein S beta gene
      leading to double homologous unequal crossing-over or gene conversion of a short
      DNA sequence. However, this is unlikely since none of the 7 other protein S beta
      specific nucleotides are present in the mutated exon XII sequence of the protein
      S alpha gene. The common Arg506-->Gln Leiden mutation in coagulation factor V is
      not an additional risk factor for thrombosis in any of the four families studied.

PMID- 8865521
TI  - Combined hereditary disorders of haemophilia B Leyden (-6 G-->A) and type 1 von
      Willebrand disease.
AB  - Multiple coagulation disorders are unusual. We report here a combination of
      haemophilia B Leyden with type 1 von Willebrand disease (vWD) affecting different
      members of the same family. Haemophilia B Leyden was due to a -6 G-->A mutation
      within the promoter of the factor IX gene and was responsible for a mild
      haemophilia in the father of the proband. The proband and her sister (age 4 and
      6) exhibited a twofold lower level of factor IX activity (0.4 IU/ml) than the
      paternal grandmother (0.95 IU/ml). The differences in F IX levels in the three
      carriers of the same -6 G-->A mutation suggest the implication of an age-related
      mechanism responsible for the increase in factor IX plasma level. Haemophilia B
      Leyden patient and carriers suffered also from a mild von Willebrand disease. The
      diagnosis of this associated type 1 vWD was performed by assaying plasma von
      Willebrand factor together with multimer electrophoretic studies and DDAVP test.
      The inheritance of this vWD was investigated by haplotype analysis of the vWF
      gene. Individuals affected by such an association are actually asymptomatic, but
      per- and post-operative bleeding risk remains to be evaluated.

PMID- 8865522
TI  - Regulation of serum thrombopoietin levels by platelets and megakaryocytes in
      patients with aplastic anaemia and idiopathic thrombocytopenic purpura.
AB  - To clarify the regulatory mechanism of thrombopoietin (TPO, c-Mpl ligand) in
      chronic thrombocytopenic conditions, we determined TPO levels in the sera of
      patients with aplastic anaemia (AA; n = 26) and idiopathic thrombocytopenic
      purpura (ITP; n = 32) by an enzyme-linked immunosorbent assay. Despite a
      similarity in platelet counts, serum TPO levels in the AA group were markedly
      higher than those in the ITP group: 20.41 +/- 9.71 f mol/ml (mean +/- SD) and
      1.66 +/- 0.55 f mol/ml, respectively, both of which were significantly elevated
      compared to normal subjects (n = 41; 1.22 +/- 0.37). In both groups, serum TPO
      level showed an inverse correlation with the platelet count. We determined the
      megakaryocyte volume using bone marrow clot section and found that it was
      markedly small in the AA group; while in the ITP group it was augmented with a
      correlation to serum TPO level. Our findings suggest that TPO levels may be
      regulated not only by platelets but also megakaryocytes in AA and ITP.

PMID- 8865523
TI  - Association of factor VII:C levels with environmental and genetic factors in
      patients with ischaemic heart disease and coronary atheroma characterised by
      angiography.
AB  - Elevated Factor VII:C (FVII:C) levels are an independent risk factor for acute
      myocardial infarction. To examine the association between FVII:C levels, genetic
      and environmental factors in patients with a history suggestive of ischaemic
      heart disease, 270 patients were studied. FVII:C levels were significantly
      associated with the Msp I and promoter insertion polymorphisms. FVII:C correlated
      with environmental factors, and these correlations remained when analysed by
      genotype. In a multiple regression model, genotype, body mass index, cholesterol,
      triglycerides and gender remained as independent and significant predictors of
      FVII:C levels. There was no significant difference in FVII:C concentrations with
      severity of atheroma, or in patients with a history of myocardial infarction.
      These findings provide further evidence linking FVII:C with Msp I and promoter
      insertion genotypes and with environmental factors in established IHD, but
      suggest there is not a genotype-environment interaction or a relationship between
      FVII:C levels and severity of ischaemic heart disease.

PMID- 8865524
TI  - Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and
      patients with stable angina pectoris.
AB  - Elevated plasma fibrinogen levels are associated with an increased risk for
      cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation
      of blood platelets and it also has been described that ticlopidine can decrease
      the plasma fibrinogen level in patients with vascular diseases. The mechanism of
      this decrease has not yet been elucidated and therefore mechanisms that are known
      to affect fibrinogen levels were studied, viz, the acute phase reaction, total
      fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the
      fibrinogen beta-gene. The fibrinogen lowering effect of ticlopidine was studied
      in 26 healthy volunteers, selected on genotype of the Bcl] polymorphism of the
      fibrinogen beta-gene, and in 26 patients with stable angina pectoris in a double
      blind, randomized cross-over study. Functional plasma fibrinogen levels were
      measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and
      TDP levels were measured using an enzyme immuno assay (EIA). In the healthy
      volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p =
      0.005 using the paired Student l-test) after 4 weeks of 250 mg bid ticlopidine
      administration, whereas fibrinogen antigen, CRP and TDP levels were not
      significantly changed. In the stable angina pectoris patients the pre-treatment
      fibrinogen, CRP and TDP levels were significantly higher than in the volunteer
      group. After four weeks 250 mg bid ticlopidine administration the functional
      fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the
      fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels
      of functional and antigen fibrinogen, CRP and TDP did not change significantly
      during the placebo period in the volunteers or the patients. Neither in the
      volunteers nor in the patients was the effect of ticlopidine on the fibrinogen
      levels associated with the fibrinogen beta-gene polymorphisms. Therefore, the
      fibrinogen lowering effect of ticlopidine is likely to be a modulation of the
      functionality of the molecule and unlikely to be modulated by the acute phase
      reaction, TDP-levels or the fibrinogen beta-gene polymorphisms.

PMID- 8865525
TI  - Gemfibrozil reduces thrombin generation in patients with combined
      hyperlipidaemia, without influencing plasma fibrinogen, fibrin gel structure or
      coagulation factor VII.
AB  - A double-blind, placebo-controlled, cross-over study was conducted in 21 men with
      combined hyperlipoproteinaemia to examine if lipid-lowering treatment with
      gemfibrozil (10-12 weeks) affects blood coagulation and fibrin gel structure at
      rest or during mental stress. Gemfibrozil lowered plasma triglycerides by 57 +/-
      4%, whereas high density lipoprotein (HDL) cholesterol increased by 22 +/- 5%.
      Gemfibrozil lowered the triglyceride content of low density lipoprotein (LDL).
      Gemfibrozil reduced the plasma concentrations of thrombin-antithrombin complex
      (TAT) and prothrombin fragment F1 + 2 (F1 + 2), both at rest and during mental
      stress. However, there were no effects of gemfibrozil treatment on the plasma
      concentrations of fibrinogen, factor VII antigen, activated factor VII (VIIa) or
      activated factor XII (XIIa), or on fibrin gel structure. Acute mental stress per
      se did not influence coagulation factors, reaction products or fibrin gel
      structure, or their responses to the study drug. Thus, gemfibrozil reduced
      thrombin generation in men with combined hyperlipoproteinaemia, without
      influencing the plasma levels of fibrinogen, VIIa and XIIa, or fibrin gel
      structure. Attenuation of thrombin generation may contribute to the primary
      preventive effects of gemfibrozil on coronary heart disease.

PMID- 8865526
TI  - Association between high values of D-dimer and tissue-plasminogen activator
      activity and first gastrointestinal bleeding in cirrhotic patients. CALC Group.
AB  - Cirrhotic patients with decompensated state and high serum levels of fibrin(ogen)
      degradation products are at high risk of bleeding. The aim of this study was to
      further analyse the relationship between hyperfibrinolysis and bleeding in
      cirrhosis by measuring plasma values of D-dimer and tissue plasminogen activator
      (t-PA) activity. One-hundred-twelve cirrhotic patients with oesophageal varices
      and without previous upper-gastrointestinal bleeding entered the study and were
      followed-up for 3 years. Patients were considered to have hyperfibrinolysis if
      they concomitantly had high values of D-dimer and t-PA activity. During the
      follow-up 34 (30%) patients bled. They had more severe liver failure (p = 0.0001)
      and variceal size (p = 0.0031) and higher prevalence of ascites (p = 0.0003),
      varices with red signs and hyperfibrinolysis (p = 0.0001) than patients who did
      not bleed. Multivariate analysis disclosed hyperfibrinolysis as the only marker
      predictive of bleeding (Hazard Ratio = 42.5, p < 0.001). Our findings suggest
      that screening for hyperfibrinolysis may be useful to identify cirrhotic patients
      at risk of bleeding.

PMID- 8865527
TI  - An alternative elastase-mediated degradation of fibrinogen and fibrin observed in
      a patient with herpes simplex encephalitis and pneumonia.
AB  - A 74-year-old female developed pneumonia following herpes simplex encephalitis.
      Her white blood cell counts reached 28,400/microliters, about 90% of which
      consisted of granulocytes. The polymorphonuclear (PMN) elastase/alpha 1
      antitrypsin complex levels increased and reached the maximum of 5,019 ng/ml,
      indicating the release of a large amount of elastase derived from the
      granulocytes. The mechanism of PMN elastase release was most likely to be
      granulocyte destruction associated with phagocytosis. The cleavage of fibrinogen
      and fibrin by PMN elastase, independent of plasmin, was indicated by the presence
      of the fragments in immunoprecipitated plasma from the patient corresponding to
      elastase-induced FDP D and DD fragments and the absence of fragments
      corresponding to plasmin-induced FDP D and DD fragments on SDS-PAGE. These
      findings suggested that the large amount of PMN elastase released from the
      excessive numbers of granulocytes in this patient with herpes simplex
      encephalitis and pneumonia, induced the cleavage of fibrinogen and fibrin without
      the participation of plasmin.

PMID- 8865528
TI  - Deep venous thrombosis and lupus anticoagulant. A case-control study.
AB  - BACKGROUND: A definite evidence in favour of an association of deep-vein
      thrombosis (DVT) with lupus anticoagulant (LA) in patients free from systemic
      lupus erythematosus is still lacking. METHODS: In a case-control study, LA was
      determined in 176 consecutive outpatients who underwent phlebography because of
      the first episode of clinically suspected DVT of lower limbs. The association
      between DVT and LA was described using odds ratios (OR). RESULTS: Contrast
      venography confirmed the clinical suspicion in 59 patients (33.5%). LA was
      detected in 5 of the 59 patients with DVT (8.5%), and in none of the 117 subjects
      with normal venogram (P = 0.007). The OR for having an acute DVT in patients with
      LA was 10.7 (95% CI: 1.2-94.2). CONCLUSIONS: LA is significantly associated with
      DVT in symptomatic patients. Further studies are needed to establish the clinical
      implications of this association.

PMID- 8865529
TI  - Coagulation activation and fibrinolytic imbalance in subjects with idiopathic
      antiphospholipid antibodies--a crucial role for acquired free protein S
      deficiency.
AB  - To explore the coagulation/fibrinolytic balance and its relation with free
      protein S (f-PS) in subjects with antiphospholipid antibodies (aPLs) outside the
      setting of autoimmune inflammatory disorders, we carried out a cross-sectional
      study on 18 thrombotic patients with primary antiphospholipid syndrome and 18
      apparently healthy subjects with persistence of idiopathic aPLs. Prothrombin
      fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT) and D-Dimer (D-D)
      were taken as markers of thrombin generation and fibrin turnover. Mean F1 + 2
      levels were higher in thrombotic (p = 0.006) and non-thrombotic subjects (p =
      0.0001) than in controls as were those of D-D (p < 0.0001 and p = 0.003
      respectively). TAT levels did not differ. Lower mean levels of f-PS were found in
      thrombotic (p = 0.0006) and non-thrombotic subjects (p = 0.002) than in controls.
      Within both groups, mean F1 + 2 levels were higher in subjects who had low f-PS
      levels compared to those with normal f-PS levels (p = 0.01). Gender analysed data
      revealed blunted tPA release (venous occlusion test) in thrombotic females (from
      16.80 +/- 0.79 to 21.3 +/- 3.9 ng/nl, NS) but not in thrombotic males (from 18.2
      +/- 2.0 to 33.7 +/- 4.9 ng/ml, p=0.01) nor in asymptomatic subjects of either
      sex. Also, in both patient groups females had higher mean PAI than males (p <
      0.0002) and than control females (p < 0.02). Low free protein S was found in 100%
      of non-thrombotic and in 90% of thrombotic patients with defective fibrinolysis.
      These data are consistent with increased thrombin generation, accelerated fibrin
      turnover and fibrinolysis abnormalities also in asymptomatic carriers of aPLs and
      highlight a central role for acquired f-PS deficiency in the thrombotic tendency
      of the antiphospholipid syndrome.

PMID- 8865530
TI  - Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the
      initial treatment of acute deep vein thrombosis.
AB  - The aim of the study was to compare the efficacy and safety of once-daily
      subcutaneous injection of dalteparin, a low molecular weight heparin, with that
      of intravenous unfractionated heparin in the treatment of deep venous thrombosis
      (DVT). Patients were included if they had deep venous thrombosis distal to
      inguinal ligament and were randomised either before, if it was considered
      necessary, or after phlebographic verification of the diagnosis. There was no pre
      inclusion treatment with unfractionated heparin. One hundred and twenty patients
      received dalteparin, administered subcutaneously once-daily at a fixed dose of
      200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous
      infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the
      first or second day, and initial treatment with dalteparin or UFH discontinued
      when the prothrombin time was in the therapeutic range (2 < INR < 3) on two
      consecutive days. Control phlebograms were taken within 4 days, thereafter. There
      were no significant differences between the two initial treatment groups in
      improvements in Marder score. Two major bleeding events occurred in the UFH group
      versus none in the dalteparin group. One patient in each group experienced
      clinically significant pulmonary embolism. During a mean follow-up period of 6.9
      +/- 1.5 months, recurrent DVT occurred in four patients in the dalteparin group
      and in two of the UFH group. These results confirm those of a previous study on
      dalteparin in the initial treatment of DVT, and suggest that dalteparin
      administered once-daily at a fixed dose of 200 UI/kg is as effective and well
      tolerated as UFH in patients with DVT below the inguinal ligament. The present
      study also demonstrates that dalteparin can be started as soon as the diagnosis
      of DVT is suspected and without pre-treatment with UFH. Given that the
      administration of once-daily subcutaneous injections needs not require a patient
      to be hospitalised, studies to investigate the possibility of using dalteparin
      for the initial treatment of DVT in the outpatient setting are warranted.

PMID- 8865531
TI  - Immunological aspects of recombinant factor VIIa (rFVIIa) in clinical use.
AB  - Patients, receiving rFVIIa for treatment of bleeding disorders, have been
      followed for specific antibody formation. No antibodies against FVII were
      demonstrated in 170 patients, with hemophilia, or with acquired inhibitors to
      clotting factors. Of 6 FVII-deficient patients, one overdosed patient developed
      antibodies to human FVII. There was no indication of de novo formation of
      antibodies to potential contaminating foreign protein, which could be correlated
      to the rFVIIa treatment. Except for the FVII-deficient population, which may
      represent a risk group, rFVIIa appears to be immunologically safe for use in
      patient groups with bleeding disorders, including hemophilia A and B patients.

PMID- 8865532
TI  - The propeptides of human protein C, factor VII, and factor IX are exchangeable
      with regard to directing gamma-carboxylation of these proteins.
AB  - The specificity of the propeptide sequence in directing vitamin K-dependent post
      translational gamma-carboxylation has been assessed by examination of the extent
      of processing of chimeric constructs of blood coagulation factor VII (fVII),
      factor IX (fIX) and protein C (PC). One chimera consisted of a protein in which
      the gamma-carboxyglutamic acid (Gla)/helical stack domain of PC (amino acid
      residues 1 to 46) was replaced by that of fIX (residues 1 to 47) in an otherwise
      intact PC. Another consisted of the same construction of a fVII/PC Gla domain
      based mutant protein. The final chimera contained the leader/propeptide sequence
      of PC (residues -42 to -1) replaced by that of fIX (residues -46 to -1). In each
      case, all Glu-precursor Gla residues in the Gla domains of the proteins were
      fully processed to Gla. These results demonstrate that the propeptides of fIX and
      PC are capable of directing gamma-carboxylation of the Gla regions of either
      protein, that the propeptide of PC can fully function in gamma-carboxylation of
      the Gla region of fVII, and further suggest that, with regard to gamma
      carboxylation, communications between the propeptides and Gla domains in intact
      proteins are general in nature.

PMID- 8865533
TI  - Factor V enhances the cofactor function of protein S in the APC-mediated
      inactivation of factor VIII: influence of the factor VR506Q mutation.
AB  - Factor V and protein S are cofactors of activated protein C (APC) which
      accelerate APC-mediated factor VIII inactivation. The effects of factor V and
      protein S were quantitated in a reaction system in which plasma factor VIII was
      inactivated by APC and the loss of factor VIII activity was monitored in a factor
      X-activating system in which a chromogenic substrate was used to probe factor Xa
      formation. Factor V increased the rate of APC-mediated factor VIII inactivation
      in a dose-dependent manner in representative plasma samples with protein S or
      factor V deficiency, abnormal factor V (heterozygous or homozygous for factor
      VR506Q), or a combination of heterozygous protein S deficiency and heterozygous
      factor VR506Q. This effect was much less pronounced in the plasma samples with a
      decreased protein S level, but the impaired response in these plasmas was
      corrected by addition of protein S, indicating that both factor V and protein S
      are required for optimal inactivation of factor VIII by APC. The effects of
      factor V and protein S were also studied in a reaction system with purified
      proteins. APC-catalysed factor VIII inactivation was enhanced 3.7-fold in the
      presence of 1.1 nM factor V and 1.5-fold in the presence of 2.4 nM protein S.
      When both 1.1 nM factor V and 2.4 nM protein were present the rate enhancement
      was 11-fold. Factor V is a more potent cofactor than protein S, as can be
      concluded from the fact that 0.04 nM factor V gave the same stimulation as 2.4 nM
      protein S. Protein S lost its cofactor function after complexation with C4b
      binding protein, which indicates that it is free protein S that acts as a
      cofactor. To investigate the effect of the R506Q mutation in factor V on APC
      mediated factor VIII inactivation, factor V was purified from the plasma of
      patients homozygous for factor VR506Q. In the absence of protein S, factor VR506Q
      did not enhance factor VIII inactivation by APC, but in the presence of 2.4 nM
      protein S a slight enhancement was observed. The APC cofactor activity of factor
      V was lost when factor V was activated with thrombin or with the factor V
      activator from Russell's viper venom. These data indicate that optimal
      inactivation of factor VIII by APC requires the presence of an intact factor V
      molecule and free protein S.

PMID- 8865534
TI  - Tissue factor pathway inhibitor production by human mesangial cells in culture.
AB  - Fibrin formation within the glomeruli has been observed in various forms of human
      and experimental glomerulonephritis and it may play an important role in
      progressive glomerular injury. Furthermore it has been hypothesized that
      glomerular fibrin deposition may occur through activation of either the intrinsic
      or extrinsic coagulation pathway. It has been demonstrated that a procoagulant
      activity (PCA) which is compatible with tissue factor is present in the glomeruli
      and becomes increased in human proliferative glomerulonephritis and in animal
      models of nephritis. Tissue factor pathway inhibitor (TFPI) regulates the
      extrinsic pathway of blood coagulation through its ability to inhibit tissue
      factor activity. TFPI is present in plasma and in platelets, and it is now
      thought to be produced mainly by endothelial cells. We examined whether human
      mesangial cells (HMC) could produce TFPI and attempted to clarify regulatory
      factors which affect TFPI production. Cultured HMC were used and TFPI in the cell
      supernatants was measured by ELISA using a specific antibody. Cultured HMC showed
      the production of TFPI. Immunoblot analysis revealed 40 kD protein of TFPI. The
      concentration of TFPI was significantly increased following the incubation with
      thrombin and heparin, including low molecular weight heparin, in a dose- and time
      dependent manner. However, fetal calf serum, phorbol myristate acetate,
      lipopolysaccharide, IL-1 beta and tissue factor did not stimulate TFPI synthesis.
      Our data show that cultured HMC have the ability to produce TFPI which inhibits
      fibrin formation. It is possible that thrombin-induced enhancement of TFPI
      synthesis may be caused by the autoregulatory system of blood coagulation and
      that with heparin it may represent another anticoagulatory effect of heparin.

PMID- 8865535
TI  - beta 2 glycoprotein-I inhibits factor XII activation on triglyceride rich
      lipoproteins: the effect of antibodies from plasma of patients with
      antiphospholipid syndrome.
AB  - It is now well recognised that antiphospholipid antibodies are associated with
      thrombosis and recurrent fetal loss. Some antiphospholipid antibodies (aPAs) have
      been shown to require a cofactor, beta 2 glycoprotein-I (beta 2 GPI), for binding
      to phospholipids, and recently beta 2 GPI has been identified as the antigenic
      target for some aPAs. beta 2 GPI possesses in vitro anticoagulant properties and
      modulation of beta 2 GPI function may therefore result in altered haemostatic
      regulation. In the present study, the influence of plasma derived aPAs and beta 2
      GPI on factor XII activation on the surface of very low density lipoprotein
      (VLDL) was investigated. Factor XIIa generation was dependent on lipoprotein
      lipase treatment of VLDL and beta 2 GPI inhibited the factor XIIa generation in a
      concentration dependent manner. No consistent effects on factor XIIa generation
      were demonstrated with the IgG fractions from patients with aPAs. Inhibition of
      the beta 2 GPI activity was demonstrated by some antibodies, and study with
      cardiolipin affinity purified antibody indicated that antibody concentration is
      critical. These results suggest that perturbation of beta 2 GPI function may
      contribute to the pathogenic mechanism for thrombosis in some patients with aPAs.

PMID- 8865536
TI  - The VITA Project: population-based distributions of protein C, antithrombin III,
      heparin-cofactor II and plasminogen--relationship with physiological variables
      and establishment of reference ranges.
AB  - A proper laboratory diagnosis of inherited thrombophilia due to defects of the
      coagulation system may be obtained only by a stringent definition of the
      diagnostic reference ranges taking into account the influence exerted by major
      physiological variables. To this purpose, we analyzed the data for Protein C,
      Antithrombin III, Heparin-Cofactor II and plasminogen coming from the first 4,000
      subjects enrolled in the VITA Project. This is the first study that allows the
      establishment of reference ranges in a non-selected, active population using
      stringent standardization of clinical and laboratory measurements and
      multivariable regression techniques for data analysis. Serum triglycerides and
      total cholesterol, together with plasma fibrinogen were found to influence the
      functional plasma level of the four considered proteins. Menopause increased AT
      III concentration, while pill use increased Heparin-Cofactor II and plasminogen.
      PT and PTT ratio, gender, age, smoking, body-mass index, HDL cholesterol and
      blood group had minor effects. The effect of these variables should be taken into
      account for both clinical and epidemiologic purposes, using appropriate reference
      ranges or covariance analysis for adjustment.

PMID- 8865537
TI  - Non neutralizing antibodies to tissue type plasminogen activator in the serum of
      acute myocardial infarction patients treated with the recombinant protein.
AB  - Recombinant tissue-type plasminogen activator (rt PA) is currently used as a
      thrombolytic agent in the management of acute myocardial infarction (AMI). Since
      it is known that other recombinant proteins induce antibody formation when
      administered to humans, we determined the presence of anti-rt-PA antibodies in
      serial blood samples from 60 AMI patients (43 treated with and 17 without rt-PA).
      Blood samples were taken upon hospital admission, 15 days and 1, 3, 6 months
      thereafter. A blood sample was also collected from 200 healthy subjects. Using an
      ELISA, anti-rt-PA antibodies were detected as serum immunoglobulins specifically
      binding immobilized rt-PA, AMI patients before treatment and normal subjects
      exhibited negligible levels of anti-rt-PA antibodies; both groups had only one
      outlier value. Fifteen days after rt-PA treatment, 2 AMI patients showed an
      increase in antibody titer beyond the highest normal value. This titer
      progressively decreased during the following 6 months. The antibodies from these
      two patients bound rt-PA both in a solid and fluid phase. They bound melanoma t
      PA to a lower degree and did not bind urokinase type plasminogen activator at
      all, indicating specificity for t-PA. The marked temporal relationship between rt
      PA infusion and antibody appearance indicated that antibody formation had been
      elicited by the infusion of rt-PA. Nevertheless, the lack of anti-rt-PA antibody
      interference with rt-PA function in vitro, along with the favourable clinical
      outcome of those patients having such antibodies would indicate that the
      appearance of anti-rt-PA antibodies does not interfere with the physiological
      fibrinolytic activity.

PMID- 8865538
TI  - Probenecid inhibits platelet responses to aggregating agents in vitro and has a
      synergistic inhibitory effect with penicillin G.
AB  - Probenecid is an anion channel blocker and uricosuric agent, originally developed
      to slow the rate of excretion of penicillin. It is now also administered with
      many other drugs to reduce their required dosages. Recently, probenecid (2.5 mM)
      has been used to prevent leakage of fura-2 or fluo-3 when these indicators of
      cytosolic Ca2+ levels have been introduced into cells. However, we found that
      probenecid markedly inhibited the increases in cytosolic Ca2+ caused by ADP,
      thrombin, the thrombin receptor-activating peptide (SFLLRN, TRAP), ADP, sodium
      arachidonate, the thromboxane A2 (TXA2) mimetic U46619, and platelet-activating
      factor (PAF). This finding precluded the use of probenecid with platelets in
      measurements of cytosolic Ca2+ with indicators such as fura-2. We then
      investigated the effects of probenecid on aggregation and release of 14C
      serotonin from prelabeled platelets. Responses to all the agonists were inhibited
      by 2.5 mM probenecid, but concentrations as low as 0.25-0.5 mM inhibited
      responses to agonists that act largely via TXA2 (collagen, sodium arachidonate
      and U46619). Collagen-induced TXA2 formation was inhibited in a dose-dependent
      manner. Responses of aspirin-pretreated platelets to thrombin, SFLLRN, U46619 and
      PAF were also inhibited by probenecid, indicating that prevention of TXA2
      formation does not account for all the inhibitory effects. The combination of
      probenecid with penicillin G produced additive or synergistic inhibition of
      platelet responses; responses dependent on TXA2 were synergistically inhibited by
      concentrations of the drugs that are reached in vivo. The synergistic inhibitory
      effect of probenecid on platelet functions could further impair hemostasis if it
      has already been partially compromised by the administration of other drugs.

PMID- 8865539
TI  - The largest isoform of platelet membrane glycoprotein Ib alpha is commonly
      distributed in eastern Asian populations.
AB  - Platelet membrane glycoprotein Ib alpha has at least two polymorphisms which
      affect phenotype. One is the dimorphism at codon 145, and the other is a
      molecular weight polymorphism due to variable numbers of tandem repeats (TR) in
      the macroglycopeptide region. These two polymorphisms are in linkage
      disequilibrium. The frequencies of these polymorphisms differ considerably
      depending on race, and the largest variant with four TR is almost exclusively
      present in the Japanese population. We examined the genotypes of HPA-2 and TR
      polymorphism in three different races from Eastern Asia; the Japanese (n = 103),
      Korean (n = 101) and Chinese population (n = 177). The gene frequency of HPA-2
      differed significantly among these three populations. Among HPA-2b-positive
      individuals, the A isoform with four TR and B with three TR were present in all
      three populations and A dominated over B. Individuals homozygous for the A
      isoform were found in both Japanese and Korean populations. These findings
      indicate that the largest haplotype is common in the Eastern Asian region.

PMID- 8865540
TI  - Ionomycin-stimulated arachidonic acid release in human platelets: a role for
      protein kinase C and tyrosine phosphorylation.
AB  - Collagen (10-90 micrograms/ml) and ionomycin (1 microM; a calcium ionophore) each
      evoked rises in intracellular free calcium, protein kinase C activity and
      arachidonic acid release in human platelets, and as previously demonstrated for
      collagen, ionomycin (1 microM) stimulated protein tyrosine phosphorylation.
      However, at lower concentrations (60 and 250 nM) ionomycin selectively mobilised
      calcium. Ro31-8220 (a selective inhibitor of protein kinase C) inhibited (by 50%)
      ionomycin-stimulated arachidonic acid release. Genistein (an inhibitor of protein
      tyrosine kinases) also reduced by 50% ionomycin-stimulated arachidonic acid
      release. In combination, genistein and Ro31-8220 abolished ionomycin-stimulated
      arachidonic acid release. These findings show 1) that a rise in calcium is not
      sufficient, and 2) the activation of both protein kinase C and protein tyrosine
      phosphorylation is necessary, for full ionomycin-stimulated arachidonic acid
      release in human platelets.

PMID- 8865541
TI  - A novel mutation Gly 1672-->Arg in type 2A and a homozygous mutation in type 2B
      von Willebrand disease.
AB  - Genetic materials from 16 unrelated Japanese patients with von Willebrand disease
      (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF)
      gene, where point mutations have been found most frequent, was screened by
      various restriction-enzyme analyses. Six patients were observed to have abnormal
      restriction patterns. By sequence analyses of the polymerase chain-reaction
      products, we identified a homozygous R1308C missense mutation in a patient with
      type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five
      patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3
      vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the
      A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with
      HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism,
      either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with
      the C/T at 4891 detected with BstEII.

PMID- 8865542
TI  - Hemoglobin enhances the binding of bacterial endotoxin to human endothelial
      cells.
AB  - Human endothelial cells, when incubated with bacterial endotoxin
      (lipopolysaccharide, LPS), modify their surface in association with prominent
      production of procoagulant tissue factor (TF) activity. This deleterious
      biological effect of LPS has been shown previously to be enhanced approximately
      10-fold by the presence of hemoglobin (Hb), a recently recognized LPS binding
      protein that causes disaggregation of LPS and increases the biological activity
      of LPS in a number of in vitro assays. The present study was performed to test
      the hypothesis that Hb enhances the LPS-induced procoagulant activity of human
      umbilical vein endothelial cells (HUVEC) by increasing LPS binding to the cells.
      The binding of 3H-LPS to HUVEC was determined in the absence or presence of Hb or
      two other known LPS-binding proteins, human serum albumin (HSA) and IgG. LPS
      binding was substantially increased in the presence of Hb, in a Hb concentration
      dependent manner, but was not increased by HSA or IgG. Hb enhancement of LPS
      binding was observed in serum-free medium, indicating that there was no
      additional requirement for any of the serum factors known to participate in the
      interaction of LPS with cells (e.g., lipopolysaccharide (LPS)-binding protein
      (LBP) and soluble CD 14 (sCD14)). Hb enhancement of LPS binding also was observed
      in the more physiologic condition of 100% plasma. LPS-induced TF activity was
      stimulated by Hb, but not by HSA or IgG. In serum-free medium, TF activity was
      not stimulated under any of the conditions tested. Ultrafiltration of LPS was
      dramatically increased after incubation with Hb but not with HSA or IgG,
      suggesting that LPS disaggregation by Hb was responsible for the enhanced binding
      of LPS to HUVEC and the subsequent stimulation of TF activity.

PMID- 8865544
TI  - Factor VIII binding assay of von Willebrand factor and the diagnosis of type 2N
      von Willebrand disease--results of an international survey. On behalf of the
      Subcommittee on von Willebrand Factor of the Scientific and Standardization
      Committee of the ISTH.

PMID- 8865543
TI  - Neointima formation in injured hamster carotid artery is effectively prevented by
      the combination G4120 and quinapril.
AB  - The prevention of neointima formation by the tissue selective angiotensin
      converting enzyme (ACE) inhibitor quinapril and by the combination
      quinapril/G4120 (a platelet alpha Ub beta 3 and smooth muscle cell alpha v beta 3
      antagonist) was investigated in a hamster carotid artery injury model. Quinapril
      at 10 mg/kg/day reduced neointima formation by about 45%, 1 and 2 weeks after
      injury to the artery, i.e. significantly better than the non-tissue selective ACE
      inhibitor captopril at 100 mg/kg/day. Quinapril did not decrease the early smooth
      muscle cell (SMC) proliferation in the media, but in agreement with its
      inhibition of the carotid artery ACE activity by 62%, SMC proliferation was
      reduced by 70% in the newly forming intima. To improve the inhibition of early
      medial SMC proliferation, quinapril (10 mg/kg/day) was complemented with G4120
      (100 micrograms/kg/h). This combined treatment reduced the proliferation of
      medial SMCs to about 50% throughout the first week following injury, whereas
      intima SMC proliferation was reduced by 70% throughout treatment. Accordingly,
      the drug combination reduced neointima formation more potently than each drug
      separately by 70%. The disruption of medial elastic laminae, observed in the
      control and G4120 treated group, was consistently reduced when G4120 was
      complemented with quinapril. Thus, the present study shows in a hamster model of
      carotid artery injury, that combining drugs that prevent SMC migration and
      proliferation via different modes of action can lead to the effective prevention
      of neointima formation.

PMID- 8865545
TI  - Thrombosis in patients with heterozygous and homozygous factor XII deficiency is
      not explained by the associated presence of factor V Leiden.

PMID- 8865546
TI  - Thrombosis associated with ovarian hyperstimulation syndrome in a carrier of the
      factor V Leiden mutation.

PMID- 8865547
TI  - Prenatal diagnosis of compound heterozygous deficiency of protein C by direct
      detection of the mutation sites.

PMID- 8865548
TI  - Elevated levels of plasma endothelin-1, von Willebrand factor, and urinary
      albumin excretion in three relatives with pseudoxanthoma elasticum.

PMID- 8865549
TI  - Factor VIII inhibitor and severity of hemophilia.

PMID- 8865550
TI  - Increased stiffness of the aorta in children and adolescents with insulin
      dependent diabetes mellitus.
AB  - An ultrasonic system fitted with echo-tracking circuits was used to investigate
      the mechanical properties of the descending aorta in children and adolescents
      with insulin-dependent diabetes (IDDM). Seventy-six children and adolescents
      (aged 5-20 years) with uncomplicated diabetes and 75 age- and gender-matched
      healthy controls were examined. All subjects were normotensive. A nonlinear
      correlation between the stiffness index of the aorta and the age was found in
      both the diabetic (r = 0.47; P < 0.001) and control group (r = 0.57; P < 0.001).
      The stiffness index was higher among the diabetic subjects as compared to the
      controls (P < 0.01). No difference regarding stiffness of the aorta was found
      between genders in either of the groups. No correlation was observed between the
      stiffness index and the duration or degree of the metabolic control of diabetes.
      Our study demonstrated an increased stiffness of the aorta in children and
      adolescents with IDDM at the stage when no vascular complications were detected
      clinically.

PMID- 8865552
TI  - Correlation of histomorphology of ovarian masses with color Doppler sonography.
AB  - This study correlates the color Doppler sonography (CDS) findings in ovarian
      masses according to histomorphologic groups. Sixty-two surgically excised ovarian
      masses (31 benign and 31 malignant) in patients who underwent CDS were
      retrospectively reviewed. Lowest pulsatility index (PI) was used in benign and
      malignant unilocular cysts, septated cysts, predominantly cystic masses with
      solid components, predominantly solid masses with cystic areas and solid masses.
      The mean of the lowest PIs of benign lesions (1.7 +/- 0.7) were statistically
      significantly different (p < 0.05) from malignancies (0.7 +/- 0.3). The group of
      septated cysts (1.8 +/- 0.5 vs. 0.61 +/- 0.3) and predominantly cystic masses
      with solid areas (1.1 +/- 0.1 vs. 0.6 +/- 0.2) achieved statistical significance
      for benign vs. malignant masses. Predominantly solid masses with cystic areas
      (1.8 +/- 0.5 vs. 0.8 +/- 0.2) and solid masses (1.4 +/- 1.0 vs. 0.7 +/- 0.3) were
      not statistically significantly different. Because of a limited number of cases,
      statistically significant differences in the mean of the lowest PIs of benign vs.
      malignant unilocular cysts (2.1 +/- 0.5 vs. 1.9) could not be determined. When
      analyzed according to histomorphology, CDS findings were of predictive value in
      certain morphologies and not as much in others. This fact should be taken into
      account when evaluating an ovarian mass for malignancy with CDS.

PMID- 8865551
TI  - Variability in B-mode ultrasound measurements in the atherosclerosis risk in
      communities (ARIC) study.
AB  - The Atherosclerosis Risk in Communities (ARIC) study is a multicenter, long-term
      epidemiologic study that uses B-mode ultrasound primarily to measure carotid
      arterial intima-media wall thickness. To assess the reliability of the
      measurement process of this application of B-mode technology to population-based
      research, 36 volunteers from four centers were scanned at three visits, 7-14 days
      apart. Estimates of the components of variation in the B-mode measurements of
      artery wall thickness from between-person, between-sonographer, within
      sonographer, between-reader and within-reader variation are presented, along with
      estimates of the correlation R between measures made at repeat visits by
      different sonographers and read by different readers. The estimates of R for mean
      intima-media thickness are 0.69, 0.60, 0.54 and 0.66 for the carotid bifurcation,
      internal carotid, common carotid, and three-segment overall carotid mean,
      respectively. When these are adjusted to account for differences in between
      person variance between the ancillary study and the main ARIC study, the
      estimated site-specific reliability coefficients appropriate to the ARIC study
      population are 0.77, 0.73 and 0.70 for mean carotid far-wall intima-media
      thickness at the carotid bifurcation and the internal and common carotid
      arteries.

PMID- 8865553
TI  - Volume estimation from multiplanar 2D ultrasound images using a remote
      electromagnetic position and orientation sensor.
AB  - A system is described for calculating volume from a sequence of multiplanar 2D
      ultrasound images. Ultrasound images are captured using a video digitising card
      (Hauppauge Win/TV card) installed in a personal computer, and regions of interest
      transformed into 3D space using position and orientation data obtained from an
      electromagnetic device (Polhemus, Fastrak). The accuracy of the system was
      assessed by scanning 10 water filled balloons (13-141 mL), 10 kidneys (147-200
      mL) and 16 fetal livers (8-37 mL) in water using an Acuson 128XP/10 (5 MHz
      curvilinear probe). Volume was calculated using the ellipsoid, planimetry,
      tetrahedral and ray tracing methods and compared with the actual volume measured
      by weighing (balloons) and water displacement (kidneys and livers). The mean
      percentage error for the ray tracing method was 0.9 +/- 2.4%, 2.7 +/- 2.3%, 6.6
      +/- 5.4% for balloons, kidneys and livers, respectively. So far the system has
      been used clinically to scan fetal livers and lungs, neonate brain ventricles and
      adult prostate glands.

PMID- 8865554
TI  - Verification of cardiac doppler tissue images using grey-scale M-mode images.
AB  - Doppler tissue imaging (DTI) is a new ultrasonic technique that can be used to
      give quantified information about the motion of the myocardium. DTI M-mode
      recordings can be generated that display cardiac wall motion in great detail. In
      order to verify the motion as displayed in these images comparisons were made
      with simultaneously obtained grey-scale M-mode recordings. After capturing 135
      simultaneous DTI and grey-scale M-mode recordings, those were selected in which
      wall motion could be accurately assessed from the grey-scale recording.
      Comparison with the DTI images shows: (1) that DTI accurately displays the
      direction of wall motion; and (2) that DTI displays whether the wall is
      thickening or thinning as a velocity distribution across the heart wall. This
      information is more reliably displayed and easier to interpret in the DTI M-mode
      recordings than in the grey-scale M-mode recordings.

PMID- 8865555
TI  - Temporal correlation of blood scattering signals in vivo from radiofrequency
      intravascular ultrasound.
AB  - One limitation encountered using high frequency intravascular ultrasound (IVUS)
      is the echogenicity of blood, which increases dramatically at frequencies of 20
      40 MHz. Because of the higher velocity of moving blood particles, the echo
      pattern of flowing blood shows more variations in time than that of the wall. To
      investigate the time-varying characteristics of the blood scattering measurements
      were performed on the radiofrequency (RF) data collected in vivo from five pig
      experiments. After positioning the echo catheter inside the iliac artery, an M
      mode sequence of 30 RF traces was acquired at a high pulse repetition rate (5
      kHz). The RF correlation time was measured on the regions of blood and the
      arterial wall. Two processing techniques, temporal averaging and correlation,
      were tested for suppression of the blood echo intensity. The correlation time Tc
      measured in the blood region was approximately 1 ms, which was shorter than that
      measured in the wall region (Tc >> 6 ms). The correlation values calculated in a
      small window showed a large variation in the blood region while the wall region
      produced a constant high output. After processing eight consecutive RF traces
      (delta T = 200 microseconds), the temporal averaging method results in a 50%
      intensity reduction in the blood region. Using the correlation output as a
      weighting function, the blood echo intensity can be further reduced to only 10%
      of its original value. Application of the RF correlation processing to a cross
      sectional image data demonstrates the feasibility of this technique to remove
      most of the blood echoes and enhance the image contrast of the luminal interface.

PMID- 8865556
TI  - Volumetric flow estimation in vivo and in vitro using pulsed-Doppler ultrasound.
AB  - The measurement of volumetric blood flow in small vessels in vitro and in vivo
      poses a significant technological challenge. In this study, two pulsatile flow
      models were developed, one with a 3.2-mm lumen diameter and one with a 12.7-mm
      lumen diameter, to assess the accuracy of volumetric flow estimation of two
      pulsed-Doppler devices, a Crystal Biotech VF1 20-MHz system with either a cuff
      mounted or a needle-mounted probe and an Advanced Technology Laboratories
      Ultramark 9 High Definition Imaging system with a 5-MHz linear array transducer.
      The VF1 volumetric flow error was measured in the 3.2-mm phantom over a variety
      of pulsatile and continuous waveforms. The accuracy of the VF1 was also tested in
      porcine femoral and renal arteries. VF1 volumetric flow error ranged from 4.8% to
      54.3% in the in vivo studies. The ATL demonstrated similar volumetric flow errors
      in the porcine femoral artery (approximately 3.2 mm diameter), but these errors
      were reduced to < or = 17.4% in the 12.7-mm-diameter in vitro flow model.

PMID- 8865557
TI  - Accuracy of color doppler velocity in the flow field proximal to a regurgitant
      orifice: implications for color doppler quantitation of valvular incompetence.
AB  - Color Doppler is routinely used in estimates of valvular regurgitation. Velocity
      and subsequently flow measurements are made at about 7-10 cm from the ultrasonic
      transducer. Error in velocity measurement may occur due to spatial broadening of
      the color Doppler beam in the axial, azimuthal and lateral directions. Error in
      velocity may also occur due to wall filters since the filtering process is not
      uniform throughout the velocity range indicated by the color bar. An attempt to
      estimate this error was made using an in vitro orifice model, a numerical finite
      element model (FEM), and information from the manufacturer. We found that the
      acoustic beam spatial expansion, wall filter sensitivity and Nyquist limit (NYL)
      have to be considered simultaneously to account for errors. The combined spatial
      expansion and wall filter effect on velocity was estimated as a weighted average
      over the sample volume. The error distributions are not universal but depend on
      orifice size and flow. For a 3-mm orifice and 100 cm s NYL the overall effect was
      overestimation of low velocities and significant underestimation of high
      velocities due to the high velocity gradients inside the sample volume. For the 5
      and the 10-mm orifice the effect was less accentuated. Based on this overall
      error distribution, a correction was incorporated on color Doppler obtained data.
      The incorporated correction yielded better agreement with numerical velocity
      data. This correction is important in the application of the proximal isovelocity
      surface area (PISA) technique and the evaluation of regurgitant flowrates.

PMID- 8865558
TI  - The influence of acoustic impedance mismatch on post-stenotic pulsed-Doppler
      ultrasound measurements in a coronary artery model.
AB  - Acoustic impedance mismatch at the fluid-wall interface was shown to affect the
      spectra from an intravascular Doppler device in an in vitro model with a diameter
      typical of human coronary arteries. Measurements were obtained first under
      Poiseuille flow conditions with impedance mismatches of 0%, 7% and 12%, and then
      under stenosed conditions for the 0% and 7% mismatch cases. For the zero mismatch
      case, the Doppler spectra could be readily interpreted in terms of fluid
      mechanical phenomena. When mismatch was present, the spectra from Poiseuille flow
      exhibited multiple peaks which could not be directly related to the velocity
      profile. Also, the spectra from stenosed flow with a mismatch of 7% were similar
      to those from the zero mismatch case but did not exhibit the specific flow
      related features as clearly. These results indicate that the impedance mismatch
      alters the acoustic environment inside the model and that this causes artifact in
      the Doppler spectra.

PMID- 8865559
TI  - Comparison of Doppler signal analysis techniques for velocity waveform,
      turbulence and vortex measurement: a simulation study.
AB  - Simulated time-varying Doppler signals incorporating bandwidth, power variation
      and vortex simulation have been used to compare a number of signal analysis
      techniques with a view to optimising the accuracy of convective velocity
      waveform, spectral broadening and vortex signal estimation. The short-time
      Fourier transform (STFT), the autoregressive (AR) modified covariance estimator,
      the time-frequency pseudo-Wigner-Ville and Choi-Williams distributions and a
      partial stationarising algorithm were investigated for a range of some analysis
      parameters (such as window duration, AR model order). It was found that all
      methods could estimate the convective velocity waveform well and all the
      nonclassical methods were an improvement over the STFT for bandwidth estimation
      with the stationarising method giving the lowest error. For vortex measurement,
      using parameters that were optimum for mean frequency and bandwidth estimation,
      the stationarising, modified covariance, pseudo-Wigner-Ville with a 10-ms window
      and Choi-Williams methods gave improved performances compared with the STFT.

PMID- 8865560
TI  - Subtraction procedure for the registration of tissue perfusion with Doppler
      ultrasound.
AB  - Tissue perfusion, i.e., in muscles or parenchymatous organs, is of both
      physiological and pathophysiological interest. The measurement of tissue
      perfusion is an unsolved problem. The Doppler ultrasound method is well suited to
      this purpose. However, measurements using this technique may be disturbed by
      movements or vibrations such as heart motion, muscle trembling or vibration of
      the subsoil (i.e. the examination table). These interfering movements produce
      Doppler frequencies in the same frequency range as slowly flowing erythrocytes,
      causing artifacts to appear in the measured data. The goal of this project was to
      suppress such artifacts with the help of a subtraction procedure. The
      mathematical theory of this subtraction procedure and its implementation in a
      newly developed two channel Doppler system are presented. This system was
      successfully tested on a phantom which is able to generate flow and movement
      artifacts. Preliminary measurements in the forearms of volunteers showed that
      movement artifacts can be at least partially suppressed.

PMID- 8865561
TI  - Ablation of tissue volumes using high intensity focused ultrasound.
AB  - Successful application of high intensity focused ultrasound to cancer treatment
      requires complete ablation of tissue volumes. In order to destroy an entire
      tumour it is necessary to place a contiguous array of touching lesions throughout
      it. In a study of how best to achieve this, exposures were selected to give
      single lesions that were thermal in origin, while avoiding effects due to tissue
      water boiling and acoustic cavitation. Arrays were formed in excised bovine
      liver. Under some exposure conditions, lesions were found to merge in front of
      the focal point, and failed to cover the desired volume. Using fine wire manganin
      constantan thermocouples, temperature studies revealed a substantial rise in the
      temperature of surrounding untreated tissue. Cooling curves showed that it was
      necessary to allow surrounding tissue to cool for up to 2 min before ambient
      temperature was reached. By allowing the tissue to cool between exposures it was
      possible to form arrays of overlapping lesions thus successfully ablating the
      complete target region.

PMID- 8865562
TI  - Disturbance of cellular calcium homeostasis by in vitro application of shock
      waves.
AB  - Extracorporeally generated shock waves used in lithotripsy of urinary and biliary
      stones exhibit tissue lesions in vivo and destroy or damage cells in vitro. The
      involvement of cavitation-generated free radicals in these harmful effects is
      discussed controversially. We investigated changes in cytoplasmic calcium
      concentration and intracellular calcium localization after shock-wave treatment
      of suspended cell cultures using flow cytometry and electron microscopy and
      present evidence for the disturbance of mitochondrial Ca2+ a sequestration and,
      therefore, for a chemically induced cell injury.

PMID- 8865563
TI  - The role of cavitation in the induction of cellular DNA damage by ultrasound and
      lithotripter shock waves in vitro.
AB  - The induction of DNA strand breaks in Chinese hamster ovary cells was measured
      with the comet assay after continuous wave ultrasound or lithotripter shock wave
      exposure. Cell lysis and hydrogen peroxide production were measured to gauge the
      level of inertial cavitation activity. Significant DNA damage was found after
      2.17-MHz ultrasound exposure at 37 degrees C to 0.82 MPa for 2 min or 4 min, and
      to 0.58 MPs for 4 min. A significant portion of the damage induced at the 0.82
      MPa level was repaired by the cells when warmed. Neither exposure to 500 or 1000
      shock waves at 37 degrees C in a thin-walled tube, nor exposure to 1000, 1500 or
      2000 shock waves at 25 degrees C in a polyethylene pipette bulb produced a
      significant effect, when the flash of light from the spark-gap discharge was
      blocked. This finding was consistent with the generally lower lysis and hydrogen
      peroxide production by the shock wave exposure.

PMID- 8865564
TI  - Pitfalls in the diagnosis of origin stenosis of the coeliac and superior
      mesenteric arteries with transabdominal color duplex examination.
AB  - The purpose of this study is to evaluate the effects of respiration, localization
      of the Doppler sample, and the presence of origin stenosis on the Doppler
      parameters of coeliac and superior mesenteric arteries in 22 patients undergoing
      elective abdominal vascular reconstructive surgery under standardized stable
      anesthesia. Deep inspiration decreased peak systolic and end diastolic velocities
      of the coeliac artery origin. Proximal to distal Doppler velocities of normal
      coeliac and superior mesenteric artery origins were comparable. However, in the
      presence of an origin stenosis, the increase of Doppler velocities at the origin
      of the coeliac and superior mesenteric arteries is likely to be missed by
      transabdominal scanning.

PMID- 8865565
TI  - Effect of transcranial Doppler intensity on successful recording in Japanese
      patients.
AB  - The major limitation of transcranial Doppler sonography (TCD) is the failure to
      obtain data for all patients. The purpose of this study was to determine in
      detail the effect of increasing ultrasonic acoustic intensity on the rate of
      successful recording of intracranial blood velocity signals. The study was
      performed in 239 Japanese patients using a 2-MHz range-gated, pulsed-wave TCD.
      The middle cerebral artery flow signals were recorded at 76, 152, 228, 304, 380,
      456 and 532 mW/cm2 and the results analyzed by age, gender and intensity. The
      rate of successful recording showed significant increase with the ultrasonic
      intensity in both genders (45.7% at 76 mW/cm2 vs. 81.1% at 532 mW/cm2 in males
      and 29.5% vs. 60.7% in females). However, recording was only successful in 54% of
      aged (50-89 gamma) female patients at the highest ultrasonic intensity used. It
      should be possible to significantly increase TCD usefulness in an aging Japanese
      population by further increasing TCD acoustic intensity within safety limitation.

PMID- 8865566
TI  - Downstream determinants of pulsatility of the mean velocity waveform in the
      umbilical artery as predicted by a computer model.
AB  - An electrical analog model of the umbilicoplacental circulation that was based on
      hemodynamic measurements in fetal sheep was used to predict the mean blood
      velocity waveform in the umbilical artery. A 300% increase in placental
      resistance reduced the normally forward diastolic blood velocity in the umbilical
      artery nearly to zero. When resistance was normal, variations in umbilical
      arterial wall thickness (h) and elastic modulus (E) had little effect on the
      velocity waveform, whereas a 20% increase in radius (a) halved the ratio of the
      diastolic-to-systolic blood velocity (D/S). When placental resistance was high,
      abnormal umbilical arterial wall properties (a large, or h or E small) further
      reduced D/S. We conclude that high placental resistance, low umbilical arterial
      resistance, or a combination of high placental resistance with abnormal umbilical
      arterial wall properties are the primary downstream determinants of elevated
      pulsatility in umbilical arterial blood velocity.

PMID- 8865567
TI  - The effect of variations in transducer position and sound speed in intravascular
      ultrasound: a theoretical study.
AB  - The intravascular insonation of a blood vessel in the presence of an impedance
      interface between blood and the inner vessel wall is studied theoretically. The
      model, which uses a ray approximation, is three dimensional and allows
      consideration of arbitrary noncircular lumen shapes. Model results are presented
      for the image geometry, and the insonating intensity over the vessel wall. It is
      shown that the inner lumen can be imaged accurately with the transducer at any
      position within the lumen, and at any forward viewing angle, provided the point
      of origin of the beam is stationary. If it is not stationary but rotating with
      the same angular velocity as the beam itself, the inner vessel wall is not mapped
      accurately. A particular geometric distortion which has been observed in practice
      is predicted if the transducer is near vessel wall. Acoustic impedance interfaces
      will be encountered in vascular disease because the speed of sound in fatty
      plaque is less than in blood, whereas the speed of sound in fibrous and calcified
      plaque is greater than in blood. A simplified model representation of an
      atherosclerotic lumen in developed using a cardioid-like curve and a single
      impedance interface. Model results show that refraction at this interface leads
      to an intensity distribution which is not uniform around the lumen, and which
      depends on lumen shape and transducer position. The exception is the special case
      of a circular lumen with a centrally positioned transducer. Noncircular impedance
      interfaces encountered in vivo in vascular disease may cause considerable
      intensity distortion, particularly if the transducer is close to the wall in an
      irregularly shaped lumen.

PMID- 8865568
TI  - A three-dimensional ultrasound prostate imaging system.
AB  - We have developed a three-dimensional (3D) transrectal ultrasound imaging system,
      based on using a motorized 5 MHz transducer assembly, rotated under microcomputer
      control, to collect a series of 100 two-dimensional (2D) images, digitized by a
      video frame-grabber. These are then reconstructed into a 3D image on a computer
      workstation, permitting the prostate anatomy to be visualized in three
      dimensions, and distance and volume measurements to be performed. The accuracy of
      the distance measurements was assessed with a string test phantom, and that of
      the volume measurements with balloons of known sizes. Also, the resolution
      degradation engendered by the reconstruction algorithm was assessed by comparing
      the full-width at half-maximum (FWHM) of string cross-sectional images in the 3D
      image to their 2D counterparts. The results show that distance and volume
      measurements are both accurate to about +/- 1%, and that the reconstruction
      algorithm increases the mean FWHM by 8 +/- 3% axially and 3 +/- 3% laterally.

PMID- 8865569
TI  - A Doppler ultrasound clutter phantom.
AB  - We describe two variations of a phantom designed to evaluate the wall filters
      implemented on colour and spectral Doppler instruments. Both variations use an
      acoustic beam splitter to place the same Doppler sample volume within a motor
      driven clutter belt and a flow source, which is either a second belt (dual-belt
      phantom) or a vascular phantom (belt/vascular phantom). We used the dual-belt
      phantom to evaluate the effects of the clutter belt velocity, flow belt velocity
      and clutter-to-flow power ratio on the reported colour Doppler shifts. The
      results show that the choice of wall filter, as well as the amplitudes and
      velocities of the clutter and flow components, affect the measured Doppler
      shifts. Results obtained with the belt/vascular phantom show that colour Doppler
      shifts due to the moving fluid depend strongly on the clutter velocity and choice
      of wall filter. However, only a small dependence on Doppler signal strength was
      observed.

PMID- 8865570
TI  - Canine filariosis: general introduction.

PMID- 8865571
TI  - An updating of the occurrence of canine heartworm disease in northern Italy.
AB  - A survey was carried out in northern Italy (Veneto and Friuli Venezia Giulia
      Regions) to assess the extension of canine heartworm disease close to the classic
      hyperendemic areas of the Po Valley. A filtration test on 275 privately owned
      dogs showed a mean prevalence of 44%, with a peak of 55% in the Venice province.
      A high prevalence (17%) of occult filariosis was discovered using a serological
      test. These values fall within the medium-high range previously reported from
      other Italian areas. The provinces of Pordenone, Udine, Trieste, Treviso and
      Belluno, where no cases had been previously reported, were found to be infected.
      The distribution of the infection did not differ significantly with the dogs'
      origin or sex. The prevalence seemed to be influenced significantly (p < 0.01) by
      the hosts' age, function and degree of outdoor activity, reflecting the different
      exposure risks.

PMID- 8865572
TI  - An epidemiological study of canine filarioses in north-west Italy: what has
      changed in 25 years?
AB  - A field survey aimed at updating knowledge of the distribution and prevalence of
      filarial infections in the Piedmont region was undertaken. Blood samples were
      collected from 2628 dogs (10-15 dogs/100 km2) which had remained in the local
      area, were kept in the open overnight, were more than 2 years old and had not
      previously been treated with microfilaricidal drugs. Infection was diagnosed by a
      modified Knott test. Comparison of the results with those from a similar survey
      carried out 25 years ago showed a 3-fold increase in the size of the endemic
      area, with the colonization of new habitats, and a 4-fold increase in the
      prevalence of Dirofilaria immitis infection.

PMID- 8865573
TI  - Filariosis in foxes in Italy.

PMID- 8865574
TI  - The host-parasite relationship in canine heartworm infection in a hyperendemic
      area of Italy.
AB  - From November 1990 to June 1991, 2273 Dirofilaria immitis were collected from 175
      stray dogs euthanized in the province of Padua. The breed, sex, age and weight of
      each animal were noted. The worms were counted, sexed, differentiated as adults
      or fifth-stage larvae and weighed, and their length was measured. The host
      parasite relationship in this epidemiological situation was characterized by a
      high prevalence (67%) together with a low intensity (19) and abundance (13). The
      frequency distribution of the parasites in the population of dogs followed a
      negative binomial pattern (k = 0.3177), showing a good, stable host-parasite
      relationship. The major risk of infection was in late July and August, some new
      infections being established in October and, maybe, in November. The majority of
      dogs that acquired new infections were young animals probably because of an
      immune response in older dogs. However, the prevalences increased (p < 0.01) in
      dogs from 1 to 5 years old, in shepherd and hunting dogs compared to the other
      breeds, and in large as opposed to small dogs. Microfilaraemia (range 1
      1,883,000/ml) correlated, as a trend, with the number of adult filariae, which
      also correlated with the age and the weight of the dogs (p < 0.01). No
      significant correlations were found between the length or weight of the adult
      filariae and the data from dogs.

PMID- 8865575
TI  - The validity of some haematological and ELISA methods for the diagnosis of canine
      heartworm disease.
AB  - Examinations for heartworm (Dirofilaria immitis) were performed on 175 impounded
      dogs from a hyperendemic area of the Po Valley (Italy). Each blood sample was
      used with five haematological diagnostic methods (filtration, direct smear,
      modified Knott, clotted blood and capillary tube) and three commercial ELISA kits
      (PetChek, Diasystems, Uni-Tec). The results were compared with the true infection
      status obtained from post-mortem examination of the heart, pulmonary arteries,
      thoracic venae cavae and lungs. The prevalence of the infection by adult worms at
      necropsy was 63%. The sensitivity of the tests ranged from 60% (capillary tube)
      to 81% (Diasystems) and the specificity from 88% (filtration) to 98% (PetChek).
      The results of all the tests differed significantly (p < 0.01) from those
      obtained at necropsy. The sensitivity of the tests was also assessed with respect
      to the differing numbers of worms in the hosts. A positive correlation between
      the worm burden and the sensitivity was observed in all the tests. It is apparent
      that the ELISA methods were better able to detect cases with a low number of
      worms than the haematological tests.

PMID- 8865576
TI  - Public health problems due to Dirofilaria: the Spanish situation.

PMID- 8865577
TI  - Ocular dirofilariosis in a Frenchwoman living in Sologne (France).

PMID- 8865578
TI  - Changes in the profile of liver enzymes in newborn calves induced by
      experimental, subclinical acidosis in pregnant cows and osmotic diarrhoea.
AB  - Experimental, subclinical acidosis was induced by oral administration of
      sacharose during the last 2 months of pregnancy in 15 cows. Seven cows and their
      newborn calves were used as a control group. The liver enzyme activities in the
      serum and the blood acid-base status were determined in the 15 calves from the
      cows in the experimental group. Mannitol was administered orally to 8 calves from
      the experimental group to induce osmotic diarrhoea. It was concluded that
      subclinical acidosis in pregnant cows alters the biochemical liver profile of
      their newborn calves, affecting the aspartate aminotransferase, alanine
      transaminase, beta glucuronidase, glutamate dehydrogenase and bilirubin
      activities in the serum, which are associated with oedematous changes to the
      hepatocytes. Diarrhoea was accompanied by an increase in the alkaline phosphatase
      and gammaglutamyl transferase activities and a decrease in the total protein
      concentration in the serum. These changes were apparently related to the numerous
      necrotic foci in the liver and the proliferation of the Kuppfer cells. It would
      appear from these results that the liver damage in the newborn calves was
      associated with the subclinical, metabolic acidosis in their dams and that
      osmotic diarrhoea occurring in the neonatal period additionally impaired the
      liver function.

PMID- 8865579
TI  - The seasonal prevalence of Haemonchus species in Red Sokoto (Maradi) goats in
      Nigeria.

PMID- 8865580
TI  - Relationship of plasma lactate production to cortisol release following
      completion of different types of sporting events in horses.
AB  - Fifty-eight healthy horses were studied during five sporting events of various
      intensities and durations, namely show-jumping (n = 6), cross-country in a three
      day event (n = 30), trotting races (n = 7), galloping races (n = 7) and endurance
      rides (n = 8). Venous blood samples were collected at rest and immediately after
      exercise and analysed for plasma cortisol (CORT) and lactate (LA) levels. The
      experimental procedure was the same throughout the investigation so as to permit
      a reliable comparison between the five types of exercise. The type of event
      significantly affected both the resting (p < or = 0.05) and the post-exercise (p
      < or = 0.01) plasma CORT. The degree of exercise-induced hypercortisolaemia was
      related to both the intensity and the duration of exercise for all five sporting
      events, but the endurance ride induced the most and show-jumping the least
      serious post-exercise CORT changes. LA production was much more closely related
      to the intensity of the exercise than was CORT. It is concluded that simultaneous
      measurements of plasma CORT and LA levels may be useful to discriminate between
      different types of exercise, adjust training programmes, and improve our
      comprehension of the physiology of sport horses at exercise.

PMID- 8865581
TI  - A morphometric and functional study of the toxicity of atmospheric ammonia in the
      extrathoracic airways in pigs.
AB  - The effects of atmospheric ammonia (NH3) on the nasal and tracheal mucosa of pigs
      were investigated by morphometric and functional methods. Pigs were exposed to
      four concentrations of NH3 [5 (control), 25, 50 and 100 ppm] for 6 days in a
      specially designed air-pollutant exposure chamber. Samples were taken from the
      turbinates and the trachea, and the respiratory mucosa was examined by light and
      scanning electron microscopy. Dose-response curves to carbachol and isoproterenol
      were constructed using isolated strips of tracheal smooth muscle, with or without
      epithelium. In pigs exposed to ammonia, considerable mucosal injuries were
      observed in the turbinates but not in the trachea. The number of neutrophils in
      the epithelial layer and in the lamina propria, and epithelial hyperplasia were
      closely and significantly correlated with the concentrations of ammonia (r =
      0.894, p < 0.001; r = 0.727, P < 0.001; and r = 0.818, p < 0.001, respectively).
      Except for the lamina propria, all these changes were significant (p < 0.05) at
      ammonia concentrations as low as 25 ppm. The percentage of the surface of the
      turbinate mucosa that was ciliated tended to decrease with increasing ammonia
      concentration (r = 0.439, p < 0.082). Ammonia induced smooth-muscle
      hyperresponsiveness to carbachol with a close linear correlation between
      individual values of the carbachol-induced maximal effect and the NH3
      concentrations (r = 0.526, p < 0.003). While mechanical destruction of the
      epithelium induced an increase in Emax in the control group, no difference was
      observed between the intact and denuded strips from animals exposed to ammonia.
      The response to isoproterenol was not influenced by ammonia. It was concluded
      that quantitative histological analysis of the inflammatory infiltration and
      epithelial hyperplasia in the turbinates is a useful tool for quantifying the
      effects of atmospheric pollutants in pigs; a 6-day exposure to ammonia induces
      nasal irritation and functional disturbances of the tracheal smooth-muscle
      contractions at concentrations as low as 25 ppm.

PMID- 8865582
TI  - A polymerase chain reaction (PCR) assay for the detection of bovine herpesvirus 1
      (BHV1) in selectively digested whole bovine semen.
AB  - A PCR assay for the detection of bovine herpesvirus type 1 (BHV1) DNA in
      selectively digested whole bovine semen was developed and evaluated. A brief
      treatment with proteinase-K was used to lyse free virus, virus present in non
      sperm cells and virus adhering to the spermatozoa. Genomic bovine DNA was not
      released by this treatment. Primers and probes were based on the nucleotide
      sequence of the gD gene. BHV1 virus-spiked split samples were used as positive
      controls and the PCR products were detected by eye in ethidium bromide-stained
      agarose gels. Sequentially collected non-extended semen samples from
      experimentally infected bulls were used to compare this assay with virus
      isolation. Of a total of 162 ejaculates, 51 were found positive by virus
      isolation, whereas PCR detected BHV1 DNA in 73. PCR detected BHV1 DNA for a
      longer period after infection and reactivation. Apart from its superior
      sensitivity, this PCR assay also has the advantage of being a relatively simple
      procedure, providing results within 24 h.

PMID- 8865583
TI  - The insecticidal proteins of Bacillus thuringiensis.

PMID- 8865584
TI  - Microbiological production of lactic acid.

PMID- 8865585
TI  - Biodegradable polyesters.

PMID- 8865586
TI  - The utility of strains of morphological group II Bacillus.

PMID- 8865587
TI  - Phytase.
AB  - Of all the sources of phytase that have been studied (plant, animal, and
      microorganisms), the highest yields are produced by a wild-type strain A. niger
      NRRL 3135 (12.7 mg P/hr/ml = 6.8 microns P/ml/min = 113.9 nKat/ml) in a mineral
      salt medium in which total phosphate (4 mg %) is limiting for growth and
      cornstarch and glucose are the carbon sources. Synthesis of the enzyme is
      repressed by phosphate in the wild-type strain. Aspergillus niger NRRL 3135
      produces two phytases one with pH optima at 2.5 and 5.5 (phyA) and one with an
      optimum at pH 2.0 (phyB). It also produces a pH 6.0 optimum phosphatase that has
      no phytase activity. These three glycoproteins have been purified to homogeneity,
      characterized, sequenced, and cloned. The sequences have been compared to each
      other, other phytases, and to known phosphatases. Their homology has been
      determined. The active sites of phytases show remarkable homology to the active
      site residues of the members of a particular class of acid phosphatase (histidine
      phosphatase). The most conserved sequence is RHGXRXP. Phytase has been covalently
      immobilized on Fractogel TSK HW-75 F and glutaraldehyde-activated silicate. It
      has been immobilized on agarose. Losses of activity have been noted on
      immobilization but these may be minimized by future research. It should be
      possible to commercially produce and recover penta-, tetra-, tri-, di-, and
      monoinositol phosphates using immobilized phytase if markets develop for those
      products. Phytase (phyA) from A. niger NRRL 3135 has been cloned into an A. niger
      glucoamylase producing strain CBS 513.88 using a construct that has a glucoamylae
      promoter and an A. niger NRRL 3135 leader sequence, and that is devoid of
      phosphate repression. The yield of the secreted enzyme was increased 52-fold
      above that of wild-type A. niger NRRL 3135. The bioengineered organism produces
      270 microns P/ml/min (4500 nKat/ml) which is approximately 7.9 g/liter in the
      medium. The yield of the secreted enzyme was increased 1440-fold above that of
      wild type CBS 513.88. Commercial preparations of the cloned enzyme are available.
      Phytase (phyA) has been cloned into tobacco and canola. The enzyme is localized
      in the seed and expressed at high levels. Feeding of the seed to animals has made
      the phytin-P in the commercial diets available to the animals. The efficacy of
      feeding phytase to monogastric animals (poultry and swine) has been established.
      The amount of enzyme that is necessary to be added to commercial diets has been
      titred for broilers, layers, turkeys, ducks, and swine. The units of enzyme
      required are related to the phytin-P content in the diet. The use of the enzyme
      as a feed additive has been cleared in 22 countries. If phytase were used in the
      diets of all of the monogastric animals reared in the U.S., it would release
      phosphorus that has a value of $1.68 x 10(8) per year. The FDA has approved the
      enzyme preparation as GRAS. The effect of feeding phytase to animals enables
      assimilation of the P found in feed ingredients and diminishes the amount of
      phosphate in the manure and subsequently entering the environment. The effect of
      feeding phytase to animals on pollution has been quantitatively determined. If
      phytase were used in the diets of all of the monogastric animals reared in the
      United States, it would preclude 8.23 x 10(7) kg P from entering the environment.

PMID- 8865588
TI  - Retrospective beryllium exposure assessment at the Rocky Flats Environmental
      Technology Site.
AB  - The purpose of this study was to determine how two types of sampling data could
      be used for an exposure assessment in a beryllium shop at the Department of
      Energy's Rocky Flats Plant. Beryllium exposure was assessed via fixed airhead
      (FAH) sampling, in which the filter cassette was affixed to the machine,
      generally within a few feet of the worker's breathing zone. Approximately 500,000
      FAH samples were collected for beryllium over three decades at the site. From
      1984 to 1987, personal breathing zone (PBZ) samples also were collected as part
      of the evaluation of a new high velocity/lcw volume local exhaust ventilation
      system in the beryllium shop. FAH data indicated that four statistically
      different exposure periods existed from 1970 to 1988, as the FAH annual
      arithmetic means varied with changes in the local exhaust ventilation system and
      production levels. A matched comparison between the FAH and PBZ sample data found
      no direct linear correlation (R2 = 0.014); however, the mean PBZ results were
      higher than the mean FAH results (p = 0.0001). The mean PBZ level was 1.04
      micrograms/m3 while the FAH average was 0.16 microgram/m3 (permissible exposure
      limit for beryllium: 2 micrograms/m3). A health surveillance program to identify
      cases of chronic beryllium disease (CBD) and beryllium sensitization has been
      implemented at Rocky Flats. To date, 53 cases of CBD and 86 cases of sensitivity
      to beryllium have been diagnosed. Continuing studies are evaluating
      semiquantitative dose response relationships for CBD using the exposure data
      discussed herein.

PMID- 8865589
TI  - Respirator cartridge service-life: exposure to mixtures.
AB  - Expressions associated with a previously developed procedure to assess respirator
      cartridge service-life were modified to address the cartridge breakthrough
      properties of each of individual compounds comprising systems with more than two
      components. These were applied to specific ternary and quaternary test mixtures.
      Experimental breakthrough data were collected for (1)
      acetone/cyclohexane/toluene, (2) ethyl acetate/cyclohexane/toluene, (3)
      cyclohexane/toluene/ m-xylene, (4) ethyl acetate/cyclohexane/toluene/m-xylene,
      and (5) acetone/ cyclohexane/toluene/ m-xylene. Data indicate that as an exposure
      experiment proceeds, a compound that is adsorbed relatively weakly by the carbon
      bed may be displaced by a more strongly adsorbed component, which may result in a
      breakthrough concentration for displaced compounds that exceeds the challenge
      concentration in the mixture. The approach described accounts for the
      displacement phenomenon and can predict the ratio of the number of displaced
      molecules to the corresponding number of displacing molecules. Experimental data
      for each multicomponent system were used to determine values of three parameters
      (k', tau, and A(m)) for each compound in each challenge system. The value of k'
      characterizes the rate of adsorption of a compound under applicable experimental
      conditions, tau indicates the capacity of the charcoal, and A(m) describes the
      effectiveness of a compound in displacing a previously adsorbed compound.
      Parameter values were applied to calculate complete breakthrough curves for each
      compound of each mixture. Calculated curves were compared with corresponding
      experimental data; reasonable agreement justifies simplifying assumptions
      incorporated into the application of the approach to mixtures of more than two
      compounds. The time-dependence of the weight of each compound adsorbed by the
      carbon was calculated. The service-life of respirator cartridges exposed to
      multicomponent mixtures depends on the challenge concentration of each component
      of the system and is significantly influenced by the displacement effect. The
      adsorption capacity of the carbon and the breakthrough time for weakly adsorbed
      compounds are decreased significantly by exposure to mixtures.

PMID- 8865590
TI  - Application of the thoracic sampling definition to fiber measurement.
AB  - As part of a consideration of the sampling method for refractory ceramic fibers,
      calculations were carried out at the National Institute for Occupational Safety
      and Health to evaluate different approaches to fiber measurement. The most common
      technique for estimating fibers that can reach the lungs is to use an upper
      diameter limit of 3 microns in the phase contrast optical microscope counting
      rules. Calculations were carried out to estimate the aerodynamic diameter of
      fibers in several lognormal size distributions likely to occur in workplaces.
      Using these size distributions, the use of a 3 microns fiber diameter upper limit
      in the counting rules was compared with results expected from a sampler designed
      to collect fibers according to the thoracic definition, which is based on the
      aerodynamic diameter of compact particles. The other limits in the optical
      courting procedure, i.e., counting only fibers longer than 5 microns and thicker
      than 0.25 micron, were included in the calculations. The calculations indicate
      that the 3 microns upper diameter counting rule agrees with the thoracic
      definition within about +/- 25% for a wide range of possible fiber size
      distributions. The advantages of using a sampler designed to collect the thoracic
      fiber size fraction include reducing analyst decision making (all fibers
      collected would be counted) and reducing the nonthoracic particles on the sample,
      making the sample easier to analyze. Until thoracic samplers are available for
      fibrous aerosols, incorporating the 3 microns upper diameter limit as part of the
      criteria for counting fibers may serve as a surrogate for thoracic sampling.

PMID- 8865591
TI  - Effect of workers' shoe wear on objective and subjective assessment of
      slipperiness.
AB  - Subjective rating of slipperiness tests were conducted for 12 male industrial
      workers on three slippery surfaces, with poor or good lighting conditions, and
      with new or workers' own old shoes. A strain gauge force platform was used to
      evaluate dynamic coefficient of friction (COF) of shoes for the same surface
      conditions representing objective measurements. The shoe wear, available tread
      pattern, and hardness of old shoes were determined by instruments including a
      digital caliper, a digitizer, and a durometer, respectively. The surface effect
      was found to be highly significant on subjective ratings as well as dynamic COF
      (p < 0.0001). The correlation between dynamic COF values and subjective ratings
      was significant only for old shoes under medium oily conditions (r = 0.55, p <
      0.04). For a slightly oily surface, decreasing the percent of tread available
      significantly increased dynamic COF values (p < 0.016). In addition, the effect
      of increased shoe hardness significantly increased the available tread pattern
      when only the data from the most deteriorated old shoes were included in the
      analyses (p < 0.004). These results emphasize the need to consider subjective
      assessment of slipperiness as a valid way to evaluate floor slipperiness. Further
      study is needed to (1) evaluate the effects of physical fatigue due to workload
      on subjective assessment of slipperiness and workers' ability to assess
      slipperiness during task performance; (2) consider the effect of available shoe
      tread on COF values and slip potential; and (3) determine if guidelines should be
      developed regarding when work shoes should be replaced to reduce slip and fall
      injuries.

PMID- 8865592
TI  - Direct measurement of hexahydrophthalic anhydride in workplace air with a
      transportable Fourier transform infrared spectrometer.
AB  - A method for direct measurement of hexahydrophthalic anhydride (HHPA) in
      workplace air by use of a Fourier transform infrared (FTIR) spectrometer was
      developed. Two visits were made to a plant manufacturing capacitors where HHPA
      was used. On the first visit a calibration method was developed according to what
      was expected to give the best calibration. This was performed by collection of 82
      FTIR spectra from the air while simultaneously taking samples with a reference
      method using Amberlite XAD-2 sorbent tubes. On the second visit, two weeks later,
      the calibration method was used for prediction of HHPA concentrations (n = 52) in
      air; these were compared with XAD-2 determinations. The predicted FTIR values as
      a function of the XAD-2 determinations were used to evaluate some parameters
      regarding the FTIR method. The limit of detection was 120 micrograms HHPA/m3, and
      the precision at 150 micrograms/m3 was 22% and at 400 micrograms/m3 8%. When
      sampling from a pure HHPA atmosphere the obtained concentration by the FTIR was
      103% of that of the XAD-2 tubes. The selection of different analytical parameters
      for the determinations are also discussed. The method is a useful tool in fast
      mappings of exposure levels.

PMID- 8865593
TI  - Evaluation of real-time techniques to measure hydrogen peroxide in air at the
      permissible exposure limit.
AB  - The major occupational concern from bio-decontamination of equipment using vapor
      phase hydrogen peroxide (VHP) generation systems is potential operator exposure
      outside the protective barrier from possible VHP leaks or accidental releases
      from the sealed piece of equipment during decontamination. For this reason,
      different real time monitoring techniques were evaluated to determine their
      ability to accurately measure VHP at concentrations ranging from 0.5 ppm to 5
      ppm. The results of this laboratory evaluation suggest that two of the four
      methods evaluated (the ion mobility spectrometer [IMS] and Polytron) will
      approximate the National Institute for Occupational Safety and Health +/- 25%
      accuracy requirements for measuring the concentration of VHP at and near the
      Occupational Safety and Health Administration permissible exposure limit of 1.0
      ppm. Over the range of 0.5 ppm to 5.1 ppm VHP, the IMS had an approximate pooled
      method accuracy of +/- 21%, while the Polytron had a pooled method accuracy of +/
      22%. However, both instruments had false readings when exposed to nominal
      concentrations of methanol, bleach, and sulfur dioxide. The two additional VHP
      monitoring techniques evaluated (the single point monitor [SPM] and Draeger tube)
      were unable to accurately measure the concentration of VHP when the relative
      humidity was below 20%.

PMID- 8865594
TI  - Effects of key stiffness on force and the development of fatigue while typing.
AB  - An experiment was conducted to investigate the effect of key stiffness on the
      development of fatigue, keyboard reaction forces, and muscle electromyography
      (EMG) responses. Six subjects typed continuously for 2 hours on each of two
      keyboards (0.28 N or 0.83 N resistance keys, presented in random order). Keyboard
      reaction force and root mean square finger flexor and extensor EMG were recorded
      for 2 minutes at 250 Hz for every 10 minutes subjects typed. After typing for 2
      hours subjects were given a 2-hour rest break and then typed on the remaining
      keyboard for an additional 2 hours Fifty-four percent more peak force, 34% more
      peak finger flexor EMG, and 2% more peak finger extensor EMG were exerted while
      using the 0.83 N keyboard. Peak and 90th percentile values showed similar trends
      and were well correlated for force and finger flexor and extensor EMG. Subjects
      typed much harder than necessary (4.1 to 7.0 times harder on the 0.28 N keyboard
      and 2.2 to 3.5 times harder on the 0.83 N keyboard) to activate the keys. Fatigue
      was observed on the 0.83 N keyboard during 2 hours of continuous typing, but the
      trends were mild. It appears that the ratio of typing force to flexor EMG may not
      be a sensitive enough indicator of fatigue for low-force high repetition work.

PMID- 8865595
TI  - Who takes credit?

PMID- 8865596
TI  - Silica article clarification.

PMID- 8865597
TI  - Regarding calibration.

PMID- 8865598
TI  - Worker exposure to endotoxin, phenolic compounds, and formaldehyde in a
      fiberglass insulation manufacturing plant.
AB  - Worker exposures in a fiberglass wool insulation manufacturing plant were
      studied. The plant used a continuous process and operated at full production
      during a six-week study. Area samples were used to characterize spatial
      variability of contaminant levels. Repeated personal samples were used to
      characterize the distribution and to explore within- and between-worker
      variability of exposures. The greatest potential for exposure to each of the
      contaminants was restricted to specific areas of the plant. Area geometric mean
      concentrations were 1 to 390 ng/m3 for endotoxin and 22 to 414 micrograms/m3 for
      formaldehyde. There was considerable within-area variation of endotoxin
      (geometric standard deviation [GSD] 2.6 to 5.5) and formaldehyde (GSD 2.0 to
      4.5). Concentrations of phenolic compounds were correlated with endotoxin and
      were influenced by a relatively high limit of detection. The ranges of personal
      GM exposures across homogeneous groupings were smaller than the range for the
      corresponding areas (endotoxin 5.8 to 36.4 ng/m3; formaldehyde 18.1 to 67.4
      micrograms/m3). Variability in personal exposure was high. Individual GSDs ranged
      up to 10, with the mean individual GSD of 3.4 for endotoxin, and up to 12 with
      mean 3.7 for formaldehyde. Suggested thresholds for acute respiratory effects of
      endotoxin exposure were frequently exceeded (46% of 8-hr personal samples > 10
      ng/m3, 7% > 100 ng/m3). No personal samples exceeded the Occupational Safety and
      Health Administration permissible exposure level or the American Conference of
      Government Industrial Hygienists' threshold limit value for formaldehyde;
      however, 34% were greater than 60 micrograms/m3 and 11% were greater than 120
      micrograms/m3. Thus, exposures fell in a range where important exposure-response
      relationship could be examined.

PMID- 8865599
TI  - Development of a novel derivatization reagent for the sampling and analysis of
      total isocyanate group in air and comparison of its performance with that of
      several established reagents.
AB  - Analytical reference standards generally are not available for non-monomeric
      isocyanate species, making accurate identification and quantitation by high
      performance liquid chromatography (HPLC) difficult. A successful derivatizing
      reagent must react rapidly with all isocyanate groups, the derivatized isocyanate
      must be detectable selectively and at very low levels, and the detector used for
      quantitation must give a response proportional to the number of derivatized
      isocyanate groups present. A novel derivatizing reagent, 1-(9
      anthracenylmethyl)piperazine (MAP), was prepared in an attempt to achieve these
      goals. Derivatives were prepared by reacting five mono- and difunctional
      isocyanates with MAP and three other established isocyanate derivatizing
      reagents. These reagents included 1-(2-methoxyphenyl)piperazine (MOPP),9
      (methylaminomethyl)anthracene (MAMA), and tryptamine (TRYP). The relative
      reactivities of MAP, MOPP, TRYP, and MAMA with phenyl isocyanate were found to be
      100, 88, 30, and 25, respectively. Average molar absorptivities at the absorbance
      maxima +/- compound-to-compound variabilities were, for MAP: 1.47 x 10(5) +/-
      3.50%; MAMA: 1.38 x 10(5) +/- 7.07%: and TRYP: 3.98 x 10(4) +/- 13.1%. Average
      fluorescence responses were, for MAP: 100 +/- 32.6%; MAMA: 41.0 +/- 58.8%; and
      TRYP: 2.27 +/- 15.6%. A comparison of MAP and MOPP ureas by HPLC/ultraviolet
      (UV)/electrochemical (EC) gave average responses for UV, EC, and EC/UV for MAP:
      117 +/- 7.3%, 52.1 +/- 6.6%, and 0.447 +/- 10.7%, respectively; for MOPP: 24.3 +/
      62.5%, 76.7 +/- 28.5%, and 4.28 +/- 59.1%, respectively. The favorable
      performance of MAP warrants its further study as a reagent for the determination
      of total isocyanate group in air.

PMID- 8865600
TI  - Evaluation of 1-(9-anthracenylmethyl) piperazine for the analysis of isocyanates
      in spray-painting operations.
AB  - A new reagent, 1-(9-anthracenylmethyl)piperzine (MAP), was used for the
      derivatization of airborne 1,6-hexamethylene diisocyanate (HDI) and
      polyisocyanates generated during spray-painting operations. The new reagent,
      which offers enhanced sensitivity and uniformity of response to both the
      monomeric and oligomeric forms of HDI, was compared directly with 1-(2
      methoxyphenyl)piperazine (MOP), the currently employed derivatizing reagent used
      in the National Institute for Occupational Safety and Health Method 5521. Both
      the validity of the side-by-side sampling protocol and the efficacy of two
      derivatizing reagents were evaluated in field studies. The analytical results
      indicate that there is no significant difference at the 95% confidence level in
      the concentration of polyisocyanate in the aerosol as determined by two impingers
      containing MAP and a third containing MOP when these are positioned in a side-by
      side-by-side arrangement.

PMID- 8865601
TI  - Worker exposures to nitrosamines in a rubber vehicle sealing plant.
AB  - Occupational nitrosamine exposures were measured during a National Institute for
      Occupational Safety and Health (NIOSH) health hazard evaluation at a rubber
      vehicle sealing plant. All of the 28 personal breathing zone samples had
      detectable concentrations of nitrosodimethylamine (NDMA), nitrosodiethylamine,
      nitrosopiperidine (NPIP), and nitrosomorpholine; and 27 of the 28 samples had
      detectable concentrations of nitrosopyrrolidine. The NDMA exposures were the
      highest, ranging from 0.47 to 11.44 micrograms/m3. The next highest exposures
      were to NPIP, ranging from 0.20 to 4.39 micrograms/m3. Several general area air
      samples were also collected, which revealed concentrations of NDMA ranging from
      2.29 to 88.47 micrograms/m3 at the drills along the salt bath lines. The salt
      bath curing process appears to be the primary source of nitrosamine formation,
      and personal exposures were highest for the salt bath line operators and
      assistant operators. Although there are no numerical occupational nitrosamine
      standards in the United States to reference, the exposures in this plant were
      much higher than the German standard of 1 micrograms/m3 total nitrosamines for
      general industry and 2.5 micrograms/m3 total nitrosamines for certain processes
      such as vulcanization. NIOSH investigators recommended that the ventilation
      systems be improved to reduce the exposures to the lowest feasible concentrations
      until the process can be redesigned so that nitrosamines are not formed.

PMID- 8865602
TI  - Comparison of daily noise exposures in one workplace based on noise criteria
      recommended by ACGIH and OSHA.
AB  - The objective of this study was to determine the impact of the new American
      Conference of Governmental Industrial Hygienists (ACGIHnew) noise criteria, as
      compared to the current U.S. Occupational Safety and Health Administration (OSHA)
      hearing conservation criteria, on the number of employees to be included in the
      hearing conservation program at one industrial facility. This study also compares
      the combined effects of a 3-dB versus a 5-dB exchange rate and an 80-dBA versus a
      90-dBA measurement threshold on daily noise doses and equivalent 8-hr time
      weighted averages (TWAs). Employee noise exposures were measured using paired
      Ametek MK-3 noise dosimeters, one dosimeter set to the ACGIHnew noise criteria
      and one to the present OSHA hearing conservation criteria. Samples were collected
      over 4-hr periods (half-shifts) for 50 employees in 7 job categories. Results
      indicate that the majority of the employees' exposures fell below an 8-hr TWAOSHA
      of 85 dBA. The differences between the predicted TWAACGIHnew and the TWAOSHA
      ranged between 0.2 and 12.6 dB for paired samples, with an average difference of
      4.6 dB. Overall, these differences in employee 8-hr TWAs would project a 36%
      increase in the percent of the population enrolled in the hearing conservation
      program and a 50% increase in the percent of the population required to wear
      hearing protection.

PMID- 8865603
TI  - Hydrogenase encapsulation into red blood cells and regeneration of electron
      acceptor.
AB  - Biochemical decompression has been proposed as a method for reducing the amount
      of time required for deep-sea divers to return to the surface. Divers breathing
      H2/O2 mixtures would be presented with hydrogenase enzyme, and decompression
      would be accelerated by means of the enzymic removal of excess H2 from the
      tissues. We have studied FAD as a hydrogenase electron acceptor that is capable
      of transferring electrons derived from H2 oxidation directly to O2. Kinetic
      activity constants for the soluble hydrogenase from the bacterium Alcaligenes
      eutrophus H16 were determined with FAD, FMN and riboflavin as electron acceptors,
      and these values were compared with those obtained with the physiological
      electron acceptor NAD+. The Michaelis constants (K(m)) were similar for FAD, FMN
      and NAD. However, the maximal catalytic-centre activity (Kcat) was much lower for
      the flavins, and the catalytic efficiency (Kcat/K(m)) with FAD was 1/20th the
      value for NAD+. After enzyme-catalysed FAD reduction to FADH2, the FAD could be
      regenerated by addition of O2 and reduced again by the enzyme in the presence of
      H2. Thus FAD served as a regenerable electron shuttle between H2 and O2. H2O2, a
      by-product of FADH2 oxidation by O2, inhibited the enzyme. Much greater
      inhibition was observed with the reduced form of the enzyme. Active hydrogenase
      was efficiently encapsulated into human and pig red blood cells. Hydrogen
      consumption was seen with lysed carrier cells, but was demonstrated with unlysed
      carrier cells only when FAD was co-encapsulated along with enzyme. These results
      demonstrate that red blood cells encapsulating hydrogenase and FAD act as a
      system for continuous H2 consumption in a mammalian tissue without addition of
      exogenous factors, and such cells may provide a biotherapeutic method for
      reducing the risk and treatment of decompression sickness.

PMID- 8865605
TI  - Dynamic reaction design of enzymic biotransformations in organic media:
      equilibrium-controlled synthesis of antibiotics by penicillin G acylase.
AB  - Parameters relevant to the thermodynamically controlled synthesis of cephalothin
      utilizing highly active stabilized penicillin G acylase derivatives were studied.
      These included solubility/stability of substrates, enzyme derivative
      activity/stability, reaction course and synthetic yields. These parameters were
      altered by varying the pH, dimethylformamide concentration and temperature.
      Simultaneous optimization of the selected parameters could not be achieved with a
      single set of conditions. However, continuous adjustment of conditions throughout
      the reaction course allowed each parameter to be optimized (dynamic reaction
      design). This strategy works by optimizing those parameters that are critical to
      the overall reaction at a given point, whilst leaving others sub-optimal when
      their contribution to the total is minimal. This strategy has achieved a 90%
      transformation of antibiotic nucleus to cephalothin at a final concentration of
      20 g/l, high enzyme and reactant stability, with a reaction period of 3 h (using
      1 ml of derivative/40 ml of reaction solution).

PMID- 8865604
TI  - Refolding and purification of Cephalosporium acremonium deacetoxycephalosporin C
      synthetase/hydroxylase from granules of recombinant Escherichia coli.
AB  - The gene for bifunctional deacetoxycephalosporin C synthetase/hydroxylase of
      Cephalosporium acremonium was cloned and overexpressed as an insoluble and
      inactive enzyme in granules of recombinant Escherichia coli. About 40-60% of
      expected synthetase activity along with 50-80% protein purity could be recovered
      directly from granular extracts with only a single empirically optimized
      refolding step. Further purification to homogeneity was achieved by a single
      anion-exchange-chromatographic step in the presence of denaturing concentrations
      of urea. The main obstacle to converting the homogeneous unfolded protein into
      the active enzyme was a urea-dependent aggregation during refolding that led to
      irreversible enzyme inactivation. Information obtained from refolding studies
      using gel-filtration HPLC, fluorescence spectroscopy and disulphide analysis led
      to an optimal enzyme refolding scheme that resulted in a highly active (i.e. 65
      75% of the expected activity) and moderately stable fungal
      synthetase/hydroxylase.

PMID- 8865606
TI  - Structure and organization of albumin molecules forming the shell of air-filled
      microspheres: evidence for a monolayer of albumin molecules of multiple
      orientations stabilizing the enclosed air.
AB  - The structure and organization of albumin molecules in the shell of air-filled
      microspheres formed by sonication of a 5% albumin solution have been
      investigated. By limited proteolysis of intact microspheres, it has been shown
      that every albumin molecule in the shell may be cleaved without disintegration of
      the microsphere structure. The microsphere shell accordingly appears to be
      composed of a monolayer of albumin molecules. Most of the main cleavage sites
      identified after N-terminal sequencing of proteolytic fragments are localized in
      three distinct regions common to both native and microsphere albumin molecules:
      the extended region of the first domain, the extended region of the second domain
      and the first disulphide loop of the third domain. The similarity in the
      localization of cleavage sites in the native and microsphere albumin molecules
      suggests that the formation of microspheres implies only a limited degree of
      conformational change of the albumin molecules. The localization of the cleavage
      sites in the three-dimensional structure of albumin suggests that the shell may
      be constituted of albumin molecules in both a native-like heart-shaped form and a
      more flipped-out elongated form with different orientations.

PMID- 8865607
TI  - Expression and purification of recombinant toxicshock-syndrome toxin I.
AB  - Toxic-shock-syndrome toxin I (TSSTI), an exotoxin produced by certain strains of
      Staphylococcus aureus, has been closely associated with the pathogenesis of toxic
      shock syndrome. Outside the context of its staphylococcal host, TSSTI may offer
      therapeutic uses. We report here a strategy for high-level expression and
      simplified purification of TSSTI. We have subcloned the coding region for TSSTI
      into a vector containing an inducible T7 promoter sequence and expressed the
      protein in an Escherichia coli host strain. The recombinant TSSTI protein
      contained ten sequential histidine residues (Histag) at its N-terminus, which
      enabled its efficient purification using nickel-agarose-affinity resin. Histag
      TSSTI (H-TSSTI) was further purified to homogeneity using a size-exclusion
      column. By this system, 80 mg of highly purified H-TSSTI can be consistently
      obtained per litre of culture in under 3 days. H-TSSTI retained biological
      activity and was unaffected by the presence of the Histag, as measured in
      lymphocyte proliferation assays.

PMID- 8865608
TI  - Comparative studies of recombinant human albumin and human serum albumin derived
      by blood fractionation.
AB  - Recombinant human albumin produced in the yeast Saccharomyces cerevisial and
      human serum albumin derived from blood fractionation were compared by a series of
      analytical techniques. These demonstrated that the two proteins were equivalent
      structurally. However, differences observed in some of the assays indicated that
      the recombinant product had lower levels of structural heterogeneity than the
      blood-derived protein.

PMID- 8865609
TI  - A prototype effect and categorization of artificial polymorphous stimuli in
      pigeons.
AB  - In a go-no-go discrimination task, pigeons were trained to discriminate
      artificial polymorphous stimuli differing along 3 six-valued features. Exemplars
      of each category were generated by systematic transformations of the features
      from a single stimulus, a base pattern (prototype). They were then tested for
      transfer to novel stimuli including the base patterns. The most pronounced
      discrimination occurred between the base patterns rather than between the extreme
      positive and negative stimuli. A distance-from-prototype rule and an additive
      integration of feature utilities or of feature frequencies are suggested to
      account for the prototype effect. In Experiment 2, pigeons were trained on a 2
      key choice discrimination task, with the base patterns as conditional stimuli.
      Subsequent testing with distorted stimuli suggested that a distance-from
      prototype model best explains the present findings.

PMID- 8865610
TI  - Spatial encoding in domestic cats (Felis catus).
AB  - Four experiments were performed to identify the spatial information that cats
      used to encode the position of an object they saw move and disappear. In
      Experiment 1 and 2, several sources of allocentric spatial information were
      manipulated. Results indicated that the cats used none of these sources and
      instead relied primarily on their own spatial coordinates (pure egocentric
      information) to locate the hidden object. In Experiment 3 and 4, pure egocentric
      information was made unreliable by a detour task. Results showed that the cats
      encoded a metric source of allocentric spatial information--the relationship
      between the walls of the room and the hiding place. Together, these results
      reveal that cats' encoding of spatial information is flexible and adapted to
      various kinds of situations that can be encountered in the natural environment.

PMID- 8865611
TI  - Control of choice by the spatial configuration of goals.
AB  - Rats gathered pellets from the tops of 15.5-cm-tall poles. In a matrix of poles,
      bait was located on the tops of poles arranged in either a square (Experiment 1)
      or linear (Experiment 2) configuration. The specific locations of baited poles
      varied unpredictably from trial to trial. The data show that the rats' choices
      were controlled by the spatial configuration of baited locations. This indicates
      that the rats represented the geometric pattern formed by the locations of food.

PMID- 8865612
TI  - Cyclic responding by pigeons on the peak timing procedure.
AB  - The present experiment examined whether discrimination learning shapes the single
      peaked response distributions usually obtained with the peak procedure. Two
      sources of learning in pigeons were disclosed: learning to respond near the time
      of reinforcement on fixed interval (FI) trials and learning to withhold
      responding once the FI duration had elapsed on peak interval (PI) trials. Pigeons
      also produced a highly unexpected second peak in responding on nonreinforced PI
      trials at 3 times the FI duration. Follow-up experiments showed that a 1:4 FI:PI
      duration ratio supported double peaks, but only 1 peak was obtained with a 1:8
      FI:PI duration ratio. Finally, 4 peaks could be observed on extra-long PI trials
      under a 1:4:8 FI:PI:PI ratio procedure. The multiple-peaked response
      distributions are an unprecedented finding that present a major challenge to any
      theory of time perception.

PMID- 8865613
TI  - Retroactive interference effects of surprising reward omission on serial spatial
      memory.
AB  - Reward omission was used to produce retroactive interference in a serial delayed
      alternation task. Rats were given forced choices in 3 T mazes presented in
      succession followed by free choices in which the alternate arm in each maze was
      rewarded. Nonreward during the delay between forced- and free-choice runs
      produced a decrement in performance (i.e., retroactive interference) in
      comparison to reward during the delay. Interference in retention of the first
      maze in a list occurred when the second maze contained surprising reward or
      omission (i.e., an outcome contrary to previous training in that maze) in
      comparison to expected reward or omission. In addition to producing retroactive
      interference, omission sometimes increased alternation in the maze in which it
      occurred. These results support a differential rehearsal hypothesis of spatial
      memory.

PMID- 8865614
TI  - Bayesian analysis of foraging by pigeons (Columba livia).
AB  - In this article, the authors combine models of timing and Bayesian revision of
      information concerning patch quality to predict foraging behavior. Pigeons earned
      food by pecking on 2 keys (patches) in an experimental chamber. Food was primed
      for only 1 of the patches on each trial. There was a constant probability of
      finding food in a primed patch, but it accumulated only while the animals
      searched there. The optimal strategy was to choose the better patch first and
      remain for a fixed duration, thereafter alternating evenly between the patches.
      Pigeons were nonoptimal in 3 ways: (a) they departed too early, (b) their
      departure times were variable, and (c) they were biased in their choices after
      initial departure. The authors review various explanations of these data.

PMID- 8865615
TI  - Reinforced variability decreases with approach to reinforcers.
AB  - Anticipation of rewards had different effects on operant variability than on
      operant repetition. We reinforced variable (VAR) response sequences in groups of
      rats and pigeons and repetitive (REP) response sequences in separate groups. A
      fixed number of variations or repetitions was required per food reinforcer (e.g.,
      fixed-ratio 4). Although VAR contingencies resulted in high levels of variability
      and REP contingencies in high repetition, opposite patterns of performance
      accuracy were observed as rewards were approached. Likelihood of satisfying REP
      contingencies increased within the fixed ratio, whereas likelihood of satisfying
      VAR contingencies decreased. These opposite patterns of accuracy were also
      generated by conditioned reinforcing stimuli correlated with food. Constraints on
      variability by proximity to reinforcers may explain some detrimental effects of
      reward.

PMID- 8865616
TI  - Development of reaching during the first year: role of movement speed.
AB  - When infants first learn to reach at about 4 months, their hand paths are jerky
      and tortuous, but their reaches become smoother and straighter over the first
      year. Here the authors consider the role of the underlying limb dynamics, which
      scale with movement speed, on the development of trajectory control. The authors
      observed 4 infants weekly and then biweekly from reach onset to 1 year.
      Improvements in trajectories were not linear, but showed plateaus and regressions
      in straightness and smoothness. When infants' nonreaching movements were fast,
      their reaches were also fast, and faster reaches were also less straight. This is
      consistent with an equilibrium trajectory form of control, where development
      involves the increasing ability to stabilize the trajectory against self
      generated movement perturbations.

PMID- 8865617
TI  - Perception of auditory-visual temporal synchrony in human infants.
AB  - Using a habituation/test procedure, the author investigated adults' and infants'
      perception of auditory-visual temporal synchrony. Participants were familiarized
      with a bouncing green disk and a sound that occurred each time the disk bounced.
      Then, they were given a series of asynchrony test trials where the sound occurred
      either before or after the disk bounced. The magnitude of the auditory-visual
      temporal asynchrony threshold differed markedly in adults and infants. The
      threshold for the detection of asynchrony created by a sound preceding a visible
      event was 65 ms in adults and 350 ms in infants and for the detection of
      asynchrony created by a sound following a visible event was 112 ms in adults and
      450 ms in infants. Also, infants did not respond to asynchronies that exceeded
      intervals that yielded reliable discrimination. Infants' perception of auditory
      visual temporal unity is guided by a synchrony and an asynchrony window, both of
      which become narrower in development.

PMID- 8865618
TI  - Set size, novelty, and visual pop-out in infancy.
AB  - The effects of set size and novelty on visual pop-out in 6-month-old infants was
      assessed in a perceptual-identification (memory reactivation) paradigm in which
      infants, trained and tested in their own homes, viewed a mobile containing a
      unique novel or familiar object amidst different numbers of familiar or novel
      distractors, respectively. Unique objects of both types popped out at all set
      sizes except the largest, where there was modest evidence that familiar
      distractors speeded processing (Experiment 1). When the proportion of familiar
      targets in a display of intermediate set size was increased, however, infants no
      longer detected the familiar target (Experiment 2). These findings offer
      additional support for the proposition that visual pop-out in infants and adults
      is the some phenomenon.

PMID- 8865619
TI  - Eye movement control in reading: a comparison of two types of models.
AB  - Two classes of models have been proposed to account for eye movement control
      during reading. Proponents of the 1st class of model claim that the decision of
      when to move the eyes (reflected in fixation duration) is primarily influenced by
      the status of on-line language processing such as lexical access. Supporters of
      the 2nd class of model, however, maintain that (a) lower level oculomotor factors
      such as fixation location govern the decision of when to move the eyes and (b)
      lexical variables exert only a weak influence. In this study, fixation duration
      on low-and high-frequency target words was examined as a function of fixation
      location and the number of fixations on a target word. The data are inconsistent
      with an oculomotor model.

PMID- 8865620
TI  - Signal detection analyses of repetition blindness.
AB  - Three experiments used a signal detection model to demonstrate that repetition
      blindness (N. Kanwisher, 1987) reflects a reduction in sensitivity (d') for the
      detection of repeated compared with unrepeated visual targets. In experiment 1,
      repetition blindness (RB) was found for rapid serial visual presentation (RSVP)
      letter sequences, whether the visual targets were specified by category
      membership (vowels) or as 1 of 2 prespecified letters (e.g., A or O). In
      Experiment 2, RB was found to a similar degree even when the Ist critical item
      was displayed for twice as long as the other list items, although overall
      performance was considerably improved. Experiment 3 found RB for displays
      containing just 2 simultaneously presented letters. These results support
      Kanwisher's (1987) account of RB as a genuine perceptual effect, and rule out
      alternative accounts of RB as the result of response bias, output interference,
      or guessing biases.

PMID- 8865621
TI  - Object-centered not scene-based visual neglect.
AB  - Whether visuospatial attention accesses object-centered representations, in
      addition to location-based coordinates, was investigated in patients with
      hemispatial neglect who detected a target on the left or right of a single object
      (2 connected circles or barbell) or of 2 objects (2 unconnected circles). The
      object or objects either remained static (left circle in left space) or rotated
      by 180 degrees (left circle now in right space). Relative to the static
      condition, in the rotating condition, detection times are facilitated on the left
      (contralateral) and inhibited on the right (ipsilateral) of space even when eye
      movements are controlled. This modulation of neglect was only observed for the
      single object, but not for the 2-object displays. The findings suggest that
      attention operates on object-centered as well as on location-based
      representations, and thus accesses multiple reference frames.

PMID- 8865622
TI  - Spatially diffuse inhibition affects multiple locations: a reply to Tipper,
      Weaver, and Watson (1996).
AB  - S. Tipper, B. Weaver, and F. Watson (1996) suggest that J. Pratt and R.A.
      Abrams's (1995) failure to find inhibition of return for more than the most
      recently cued location was because their 2-target display did not adequately
      capture some of the complexity of real-world visual environments. However, Tipper
      et al. tested a special case because they always cued 3 out of 4 potential
      targets (allowing cued and uncued locations to be segregated into 2 spatial
      regions). The authors show that only the 1 most recently cued location will be
      inhibited when 2 nonadjacent targets out of 4 possible targets are cued, but both
      cued locations will be inhibited when they are adjacent. Also, only the 1 most
      recently cued location was inhibited when 3 nonadjacent targets out of 6
      potential target locations were cued. Thus, in a complex environment in which
      several cued locations are interspersed among noncued locations, inhibition of
      return will occur for only the 1 most recently attended location, consistent with
      conclusions of Pratt and Abrams.

PMID- 8865623
TI  - Variation in the application of natural processes: language-dependent constraints
      in the phonological acquisition of bilingual children.
AB  - This paper studies phonological processes and constraints on early phonological
      and lexical development, as well as the strategies employed by a young Spanish-,
      Portuguese-, and Hebrew-speaking child-Nurit (the author's niece)-in the
      construction of her early lexicon. Nurit's linguistic development is compared to
      that of another Spanish-, Portuguese-, and Hebrew-speaking child-Noam (the
      author's son). Noam and Nurit's linguistic development is contrasted to that of
      Berman's (1977) English- and Hebrew-speaking daughter (Shelli). The simultaneous
      acquisition of similar (closely related languages) such as Spanish and Portuguese
      versus that of nonrelated languages such as English and Hebrew yields different
      results: Children acquiring similar languages seem to prefer maintenance as a
      strategy for the construction of their early lexicon, while children exposed to
      nonrelated languages appear to prefer reduction to a large extent (Faingold,
      1990). The Spanish- and Portuguese-speaking children's high accuracy stems from a
      wider choice of target words, where the diachronic development of two closely
      related languages provides a simplified model lexicon to the child.

PMID- 8865624
TI  - Tone perception in Cantonese and Mandarin: a cross-linguistic comparison.
AB  - This study investigated the effects of linguistic experience on tone perception.
      Both Cantonese (in Experiment 1) and Mandarin (in Experiment 2) tones, including
      both lexical and nonlexical tones, were presented to three groups of subjects:
      Cantonese, Mandarin, and English native speakers. Subjects were asked to
      determine whether two auditorily presented tones were the same or different. The
      interval between the presentation of the two tones, and the level of interference
      during this interval, were manipulated. Native speakers did better at
      discriminating tones from their own languages than the other two groups of
      subjects, for both lexical and nonlexical tones. Subjects did worst when they
      were required to count backward during the interstimulus interval. Cantonese
      speakers were better than both Mandarin and English speakers at discriminating
      Cantonese tones, and there was no difference between Mandarin and English
      speakers, except in one condition. Mandarin speakers did better than both
      Cantonese and English speakers, and Cantonese speakers did better than English
      speakers, at discriminating Mandarin tones. Results are discussed in terms of the
      effects of language background, differences between Cantonese and Mandarin tones,
      and the nature of encoding in short-term memory.

PMID- 8865625
TI  - Stress resilience, locus of control, and religion in children of Holocaust
      victims.
AB  - Two hundred eight children of Holocaust survivors who were born after their
      parents' Holocaust experience (children of survivors; COS) and 70 children of
      parents who left Europe after Hitler's rise to power in 1933 but managed to
      escape or avoid the Holocaust (children of escapees; COE) were recruited from
      various Jewish organizations. Research was conducted using questionnaires that
      were returned by mail. Measures of stress resilience (Kobasa, 1982; Kobasa &
      Puccetti, 1983), locus of control (Nowicki-Strickland, 1973), and religion
      (Jewish identity) were administered to all participants. The COS were found to
      have less resistance to stress and to identify less with feelings of being
      Jewish. The appropriateness of using COE as a control group and the difficulty of
      incorporating the unique experiences of the parents into a research study about
      the intergenerational transmission of coping style is discussed.

PMID- 8865626
TI  - College students' judgements and perceptions of persons with AIDS from different
      risk groups.
AB  - In this analog study, 104 female and 75 male undergraduate students in the United
      States read 1 of 8 vignettes that described a person who had just received
      positive HIV antigen results. The vignettes were identical except for the sex of
      the person described and his or her risk-group membership (gay, heterosexual,
      injection-drug user, or hemophiliac). After reading the vignette, the
      participants completed questionnaires assessing (a) responsibility, blame, and
      personality characteristics of the person described in the vignette; and (b)
      their own homophobia and knowledge about AIDS. Results revealed that homophobia
      was a significant covariate that affected participants' perceptions of the person
      in the vignette. With homophobia as a covariate, the hemophiliac was judged the
      least harshly, followed by the heterosexual person, the gay person, and the
      injection-drug user. No gender differences were revealed. The injection-drug user
      was evaluated the most negatively on the personality characteristics; the other 3
      groups were rated similarly. Analyses without homophobia as a covariate revealed
      significant gender differences, suggesting that prior research findings of gender
      differences on perceptions of persons with AIDS may be attributable more to
      differential levels of homophobia than to gender of the rater.

PMID- 8865627
TI  - Risk behaviors, self-efficacy, and AIDS prevention among adolescents.
AB  - This study was conducted to investigate risk behaviors and AIDS-preventive
      variables in high school adolescents. One hundred fifty-two students in Grades 10
      through 12 were administered an AIDS-related behavior questionnaire and the
      Attitudes Toward AIDS Scale-High School Version (ATAS-HS; Goh, 1992). The results
      indicated that use of alcohol was far more common than other risk behaviors among
      the respondents. Rates of sexual intercourse and intravenous drug use were
      significantly lower than those reported in other research. Self-efficacy was
      significantly related to AIDS-preventive behavioral intentions, perceived
      knowledge, and measured knowledge about AIDS. Because the AIDS-preventive
      variables functioned differently in their relationships to sexual practices, the
      correlations suggest a pattern of co-occurrence between specific behavior
      intentions and actual AIDS-preventive behaviors (i.e., sexual experience, use of
      condoms). In addition, significant gender and grade differences were found on
      selected risk behaviors and AIDS-preventive variables.

PMID- 8865628
TI  - Gender schema and gender role discrepancy as correlates of body image.
AB  - Past studies of gender role and body image have focused on women's self-reported
      levels of femininity and masculinity as correlates of body dissatisfaction and
      eating disorders. This study explored how college-aged women's and men's self
      reported discrepancies in actual and ideal femininity and masculinity are linked
      to three measures of body image. For this group of women, physical size, but not
      gender role discrepancy, was predictive of body image. For the men, in addition
      to physical size, falling short of their masculine ideal was predictive of more
      negative body image. Results are discussed in relation to gender schema theory
      and cultural ideals of female thinness and male muscularity.

PMID- 8865629
TI  - The influences of goal-related actions and reward information on children's and
      adults' perceptions of effort expenditure and goal desire.
AB  - An action perception approach (i.e., Heider, 1958) was used to investigate the
      influences of qualitatively different goal-related actions on 2nd- and 5th-grade
      children's and college students' perceptions of actors' effort expenditure (i.e.,
      trying) and goal desire (i.e., wanting). Actors performed three repetitive
      actions or three equifinal actions within 2 reward conditions (offer of reward or
      no reward, for attempting to attain a prosocial goal). At each age level,
      perceptions of effort and want varied significantly by goal-related actions,
      whereas reward information did not emerge as an influential factor in
      differentiating perceptions of effort and want. Age-related findings suggested
      that, compared with the college students, the children overattributed trying and
      wanting to the actors. In the repetitive-actions condition, both 2nd and 5th
      graders gave significantly higher effort and want ratings than college students
      did. In the equifinal-actions condition, 2nd and 5th graders gave significantly
      higher effort ratings than college students did.

PMID- 8865630
TI  - Age- and gender-specific reference ranges for hearing level and longitudinal
      changes in hearing level.
AB  - This paper presents age-specific reference ranges for hearing level and change in
      hearing level for men and women at 500, 1000, 2000, and 4000 Hz. The percentiles
      are constructed from data obtained from persons in the Baltimore Longitudinal
      Study of Aging who were rigorously screened for otological disorders and evidence
      of noise-induced hearing loss. The resulting percentile curves represent norms
      for changes in hearing level in the absence of any known otologic disease. These
      percentile curves provide a reference for detecting when a person deviates from a
      normal pattern of change, thus helping in diagnosing problems with hearing or in
      monitoring hearing in occupational settings. The smoothed means and standard
      deviations of the hearing levels were used to construct the longitudinal
      percentiles. The percentiles for cross-sectional change were constructed using
      the skew normal distribution to allow for the percentiles to be asymmetric on
      either side of the median level. These percentiles are the first reference curves
      that (1) provide standards for hearing level changes over periods of up to 15
      years, (2) account for age differences in the distribution of hearing levels, and
      (3) are based on data from persons who have been systematically screened for
      otological disorders and evidence of noise-induced hearing loss.

PMID- 8865631
TI  - Phase delay measurements of distortion product otoacoustic emissions at 2f1-f2
      and 2f2-f1 in human ears.
AB  - The present study used distortion product otoacoustic emission (DPOAE) latency as
      a tool to provide information about the generation sites of 2f1-f2 and 2f2-f1
      DPOAEs in humans. The DPOAE 2f1-f2 is supposed to be generated near the f2 site,
      but little is known about the 2f2-f1 DPOAE processing in humans. The present work
      sought to test several hypotheses as to the possible generation of 2f1-f2 at the
      f2 site and of 2f2-f1 at the 2f2-f1 site as well as their backward reflection
      site, by comparing latencies of the two DPOAEs, under appropriate frequency
      manipulation. The effect of stimulus level was also studied. The latency values
      were calculated as the phase-lag related to the frequency shift, using the ILO92
      software. Amplitudes were lower and latencies shorter for 2f2-f1 than for 2f1-f2.
      As expected, 2f1-f2 and 2f2-f1 DPOAE latency decreased with increasing stimulus
      level and frequency. At 70 dB SPL, latencies of DPOAEs with primaries f1 and f2
      or f*1 and f*2, chosen so as to obtain 2f*1-f*2 = 2f2 - f1, were identical,
      whereas at 55 dB SPL the similarities were less obvious, suggesting two different
      generation processes. The present study suggests that the comparison of several
      DPOAE components may produce useful information about their processing within the
      cochlea.

PMID- 8865632
TI  - A comparison of t test, F test, and coherence methods of detecting steady-state
      auditory-evoked potentials, distortion-product otoacoustic emissions, or other
      sinusoids.
AB  - Sinusoids in background noise can conveniently be detected using unsegmented
      power spectra, comparing power at the signal frequency to average power at
      several neighbor frequencies. In this case, the F test is preferable to t tests
      based on rms or dB values, because of the skewed distributions of rms and dB when
      signal-to-noise ratio (SNR) = 0. F-test performance improves as the number of
      frequencies increases, to about 15, but can be degraded if the background noise
      is not white, with a slope exceeding about 10 dB for the range of frequencies
      sampled. Segment analysis, using magnitude-squared coherence (MSC) or related
      statistics, has equivalent statistical power; MSC and F each yield unbiased SNR
      estimates that have identical distributions when SNR = 0. Selection of F or MSC
      for detection of sinusoids will usually be a matter of convenience.

PMID- 8865633
TI  - The effects of reverberant blast waves on the auditory system.
AB  - Chinchillas were exposed to 1, 10, or 100 reverberant impulses at 150, 155, or
      160 dB peak SPL. The impulses were generated by one of two different shock tubes,
      each producing blast waves having a different spectral composition, with one
      emphasizing low frequencies (< 0.5 kHz) and the other midfrequencies (2-4 kHz).
      Impulses were presented at the rate of one per minute. This parametric paradigm
      yielded 18 exposure conditions with 15 animals/condition. Hearing thresholds were
      measured using auditory-evoked potentials and the sensory epithelium was
      evaluated with the surface preparation. In general, trauma increased as the total
      energy of the exposure, determined by the peak SPL and number of presentations,
      increased. The dependent variables (permanent threshold shift and sensory cell
      loss) varied in an orderly fashion across frequency as the peak and number of
      presentations were increased for both blast wave sources. There were, however,
      consistent differences between the effects of the low- and high-frequency energy
      "content" blast waves. Correlations between the dependent variables and the
      energy of exposure were highest for P- or A-weighted energies [Patterson et al.,
      J. Acoust. Soc. Am. 93, 2860-2869 (1993)].

PMID- 8865634
TI  - Psychometric functions for the discrimination of spectral variance.
AB  - An experiment was conducted to measure the shape of the psychometric function for
      the discrimination of spectral variance. The stimuli were simultaneous tone
      complexes comprised of the six octave frequencies from 250 to 8000 Hz. On each
      presentation the levels of components in dB were drawn independently and at
      random from one of two normal distributions having identical means but different
      variances (sigma N = 1 dB, sigma S = 2-10 dB). In the standard two-interval,
      forced-choice procedure, the listeners' task was to indicate which complex had
      the greater variance in component level. The shape of the psychometric function
      for all five listeners was markedly different from that of an observer limited
      only by additive internal noise. It was consistent with an observer that gives
      weight to only one or two components in the complex. However, this result was
      inconsistent with the weighting functions computed from the trial-by-trial data
      from these listeners. Both measures can be reconciled if it is assumed that
      listener weights vary from trial to trial, or that decisions are based on the one
      tone in the complex having the maximum level.

PMID- 8865635
TI  - Release from upward spread of masking in regions of high-frequency hearing loss.
AB  - The upward spread of masking was compared for 500-Hz quasifrequency-modulated
      (QFM) and sinusoidally amplitude-modulated (SAM) maskers. The modulation rate was
      20 Hz. These maskers had identical magnitude spectra but different envelopes,
      which were relatively flat for the QFM masker and strongly fluctuating for the
      SAM masker. At signal frequencies more than an octave above the masker, masked
      thresholds for the SAM masker were lower than for the QFM masker, revealing
      "masking release" (QFM-SAM masked threshold differences) exceeding 30 dB in
      normal-hearing ears. In ears with high-frequency sensorineural hearing loss, but
      normal hearing in the region of the masker, masking release was markedly reduced
      or completely absent in regions of hearing loss. The data were evaluated with a
      model of masking based on the linearized response growth (LRG) of basilar
      membrane transfer functions associated with cochlear damage in animals. The LRG
      model predicted more gradual slopes of the growth of masking and reduced amount
      of masking in regions of hearing loss. The reduced masking release seen in
      regions of hearing loss could be largely accounted for by a more rapid growth of
      response to the probe tone in regions of hearing loss.

PMID- 8865636
TI  - Intensity discrimination in the presence of random-frequency, multicomponent
      maskers and broadband noise.
AB  - This study examined the effects of multicomponent, random-frequency maskers and
      broadband-noise maskers on intensity discrimination at 1000 Hz. Maskers and
      signals were 200 ms, presented simultaneously. In the first set of conditions,
      thresholds were measured for the detection of a 1000-Hz tone in the presence of
      40 or 60 dB SPL random-frequency or noise maskers, with extensive training of
      listeners with the random-frequency masker to assure stable effects of masker
      frequency uncertainty. The random-frequency maskers had two, six, or ten
      components chosen at random from a large frequency range (300-3000 Hz, excluding
      a 160-Hz band around 1000 Hz). For these maskers, performance across the four
      listeners was very similar, showing large effects of masker-frequency
      uncertainty. For noise maskers, performance matched predictions for energy-based
      masking. In the second and third sets of conditions, intensity discrimination was
      measured at 1000 Hz for pedestals ranging from 40 to 80 dB SPL, first in
      isolation and then in the presence of the maskers. The pattern of results for
      intensity discrimination in quiet showed the expected near miss to Weber's Law,
      but poorer performance than typically observed. The addition of broadband-noise
      maskers had little effect on performance. However, random-frequency maskers
      degraded performance in nearly all conditions, with the size of the effect
      dependent on the level of the pedestal relative to the masker. Considering the
      pedestal as a tonal masker, the data were fitted with various models of combined
      masking. A simple power-law model provided excellent fits, with exponents ranging
      from 0.24 to 0.35 for the multicomponent maskers, but 1.0 (linear) for the noise.
      The results support models positing that the effects of individual maskers
      undergo nonlinear transformation before they are added, independent of the
      mechanisms which produce these effects. Because random-frequency maskers
      presumably produce informational (uncertainty-based) masking, the nonlinearity in
      this case appears central rather than peripheral.

PMID- 8865637
TI  - Across-channel processes in frequency modulation detection.
AB  - This study investigated how well listeners combine information about frequency
      changes imposed on different carrier frequencies. The pattern of frequency change
      over time was either identical or different across carriers; this is referred to
      as "coherence." Psychometric functions were measured for the detection of
      frequency modulation (FM) imposed on two sinusoidal carriers, with frequencies
      1100 and 2000 Hz. The modulation of each carrier was equally detectable, as
      determined in preliminary experiments. A continuous pink noise background was
      used to mask the outputs of auditory filters tuned between the two carrier
      frequencies. In experiment 1, the carriers were gated synchronously with l-s
      steady state duration and 50-ms raised-cosine ramps. One cycle of 5-Hz sinusoidal
      FM was used, the carrier having unmodulated "fringes" on either side of this. The
      FM on the two carriers was symmetrically located about the temporal center of the
      stimulus. The relative timing of the onset of FM (lag) between the two carriers
      was systematically varied. When the FM overlapped partially or completely in time
      across carriers, detectability for coherent FM was often better than for
      incoherent FM, especially for lag = 0, and was also often better than predicted
      on the assumption that information about the FM on the two carriers was extracted
      independently and combined optimally. When the FM did not overlap in time across
      the carriers, the detectability of the combined FM was generally equal to or
      lower than the value predicted on this assumption. In experiment 2, the long
      steady-state fringes before and after the modulation were removed, and the
      modulation always started at the same time for the two carriers. The modulation
      rate was either 2.5, 5, or 10 Hz. Again, performance for coherent FM was
      generally better than for incoherent FM. The effect of FM coherence was greater
      at the lowest modulation rate but did not vary markedly with the number of
      modulation cycles. The detectability of coherent FM was well above the value
      predicted on the assumption that information from the two carrier frequencies was
      processed independently and combined optimally. These results indicate the
      auditory system has higher sensitivity to FM when the FM is coherent across
      carriers. Possible models to account for the results are discussed.

PMID- 8865638
TI  - Effects of stimulus duration on the amplitude difference limen for vibrotaction.
AB  - Vibrotactile amplitude difference limens (DLs) were measured by the continuous
      pedestal and gated pedestal methods. In both cases, the relative DL decreased as
      a function of the intensity of the stimulus and the results, in most cases, could
      be described as a near miss to Weber's law. DLs measured by the continuous
      pedestal method were found to decrease substantially as a function of increases
      in stimulus duration over a range of 12 to 1000 ms. In contrast, DLs measured by
      the gated pedestal method were only slightly affected by changes in stimulus
      duration. It was concluded that the process of temporal summation can manifest
      itself in reducing the size of the DL in the continuous pedestal, but not the
      gated pedestal, paradigm.

PMID- 8865639
TI  - Detection of frequency modulation at low modulation rates: evidence for a
      mechanism based on phase locking.
AB  - These experiments tested the hypothesis that detection of frequency modulation
      (FM) at very low rates depends mainly on temporal information (phase locking to
      the carrier) for carriers below about 5 kHz, whereas FM detection at higher rates
      (10 Hz and above) depends mainly on changes in the excitation pattern (a "place"
      mechanism). In experiment 1, thresholds for detecting FM were measured for a wide
      range of carrier frequencies (0.25-6 kHz) for modulation rates, fm, of 2, 5, 10,
      and 20 Hz. Thresholds were determined when FM only was present and when the
      carriers in both intervals of a forced-choice trial were amplitude modulated at
      the same rate as the FM with a modulation index of 0.333. The phase of the
      amplitude modulation (AM) relative to the FM was randomly selected on each trial,
      in order to disrupt cues for FM detection based on changes in the excitation
      pattern. For carrier frequencies up to 4 kHz, the deleterious effect of the added
      AM increased with increasing fm. For the 6-kHz carrier, the deleterious effect
      was independent of fm. In experiment 2, psychometric functions were measured for
      detecting combined FM and AM of a 1-kHz carrier, with fm = 2 Hz, as a function of
      the relative phase of the modulators. The modulation depths for AM and FM were
      chosen so that each would be equally detectable if presented alone. This was done
      both in quiet and in the presence of noise designed to mask either the lower or
      the upper side of the excitation pattern. In contrast to earlier results obtained
      with fm = 10 Hz [Moore and Sek, J. Acoust. Soc. Am. 96, 741-751 (1994)], only
      small effects of relative modulator phase were found. Experiment 3, was similar
      to experiment 2, except that all measurements were done in quiet, and carrier
      frequencies of 0.25, 1.0, and 6.0 kHz were used. There were no effects of
      relative modulator phase for the 0.25-kHz carrier, small effects for the 1-kHz
      carrier, and large effects for the 6-kHz carrier. The pattern of results is
      consistent with the hypothesis that both temporal and place mechanisms are
      involved in FM detection. The temporal mechanism dominates for carriers below
      about 4 kHz, and for very low modulation rates. The place mechanism dominates for
      high carrier frequencies, and for lower carrier frequencies when stimuli are
      frequency modulated at high rates.

PMID- 8865640
TI  - Detection of auditory "events" based on amplitude and frequency modulation.
AB  - These experiments examined the ability of subjects to detect auditory "events"
      composed of a brief modulation in the temporal center of an otherwise steady
      sinusoid. In experiment 1, psychometric fluctuations were measured for detecting
      either amplitude modulation (AM) or frequency modulation (FM) composed of a
      single cycle of a raised-cosine function (either positive going or negative
      going); the modulation frequency was 10 Hz, so the event lasted for 100 ms. Then,
      psychometric functions were measured for stimuli with both AM and FM, using pairs
      of values of AM and FM that were equally detectable; pairs were always modulated
      in the same direction, so a positive amplitude excursion went together with a
      positive frequency excursion. Performance was compared with the "reference"
      detectability that would be predicted from the optimal combination of independent
      sources of information. When the AM and FM were synchronous, detectability was
      better than the reference detectability. When the FM was delayed by 100 ms
      relative to the AM, detectability was mostly equal to or less than the reference
      detectability. The better performance with synchronous AM and FM is consistent
      with an explanation based on an excitation-pattern model. Experiment 2 was
      similar to experiment 1, except that the event was a single cycle of sinusoidal
      modulation starting at 0 degree phase or 180 degrees phase. When the AM and FM
      were synchronous and in phase, detectability was better than the reference
      detectability. When the AM was delayed by 200 ms relative to the FM or had
      opposite starting phase, detectability was close to or below the reference
      detectability. However, for the case where the delay was 100 ms and the
      modulation had the same starting phase for AM and FM, detectability was better
      than the reference detectability. A control experiment using two successive
      cycles of either AM or FM showed a similar, but slightly smaller, effect. It
      appears that detectability can be enhanced when two successive events form a
      regular temporal pattern.

PMID- 8865641
TI  - Spectral cues for sound localization in cats: effects of frequency domain on
      minimum audible angles in the median and horizontal planes.
AB  - Rice et al. [Hear. Res. 58, 132-152 (1992)] classified directional properties of
      the cat's head-related transfer function (HRTF) into three frequency domains. Low
      frequencies (< 5 kHz) display a broad azimuth-sensitive spectral peak that
      establishes interaural level differences, mid frequencies (5-18 kHz) are marked
      with a single deep spectral notch that changes in frequency as a function of both
      azimuth and elevation, and high frequencies (18-50 kHz) exhibit a complex pattern
      of peaks and notches that shows extensive but less systematic changes with sound
      location. Spectral cues conveyed by the mid frequencies of broadband sounds are
      important in tasks that require cats to identify the actual location of acoustic
      stimuli [Huang and May, J. Acoust. Soc. Am. (in press)]. The present study
      investigates how directional cues conveyed by the mid- and high-frequency
      spectrum of the HRTF influence the cat's ability to discriminate between sound
      locations. Thresholds for spatial acuity were measured as minimum audible angles
      (MAAs) [Mills, J. Acoust. Soc. Am. 30, 237-246 (1958)] at positive azimuths in
      the interaural horizontal plane and at positive and negative elevations in the
      median vertical plane. The frequency domain of the noise burst had little effect
      on MAAs in the horizontal plane, but removal of high-frequency spectral
      information significantly increased thresholds at positive and negative
      elevations in the median plane. These results suggest that cats are sensitive to
      directional properties of the HRTF at frequencies above 18 kHz and may use this
      information to detect small changes in sound source elevation.

PMID- 8865642
TI  - Phase independence of pitch produced by narrow-band sounds.
AB  - Three listeners matched the pitch of a simple tone to that of narrow-band complex
      signals having different phases. The pitch matches were independent of the
      phases; the frequency of the simple tone approximately equaled the center of
      gravity of the power spectrum of each complex signal. This result is inconsistent
      with a model that calculates the pitch of a waveform as the average of
      instantaneous frequency weighted by the envelope of the waveform.

PMID- 8865643
TI  - Effects of masker gating for signal detection in unmodulated and modulated
      bandlimited noise.
AB  - Thresholds for a 400-ms 1000-Hz pure-tone signal were obtained as a function of
      masking noise bandwidth for unmodulated and square wave modulated masking noise.
      Rates of modulation were 10 and 40 Hz. Noise bandwidths were 128 Hz, 387 Hz, 921
      Hz, and 1505 Hz. The masking noise was either continuous or gated on and off with
      the signal. In general, signal thresholds were relatively constant as a function
      of noise bandwidth in unmodulated noise, and improved as a function of increasing
      noise bandwidth in modulated noise. Noise gating had little or no effect on
      signal threshold in unmodulated noise. At the 10-Hz modulation rate, signal
      thresholds were somewhat higher in gated than in continuous noise at relatively
      narrow noise bandwidths, but thresholds were similar in gated and continuous
      noise for relatively wide noise bandwidths. At bandwidths of 387, 921, and 1505
      Hz, comodulation masking release (CMR) was calculated as the unmodulated noise
      threshold minus the modulated noise threshold, corrected by the difference
      between the unmodulated noise threshold and the modulated noise threshold at the
      128-Hz bandwidths. At wide masker bandwidth, CMRs were higher for gated noise
      than for continuous noise. This was due almost entirely to the threshold gating
      effect found in the 128-Hz bandwidth condition. These results suggested that
      there was a within-channel effect for gated noise thresholds to be higher than
      continuous noise thresholds, but essentially no across-channel effect of gating.
      At the 40-Hz modulation rate, signal thresholds were similar for gated and
      continuous noise at all noise bandwidths. There was a very small but significant'
      effect for the gated noise threshold to be lower than the continuous noise
      threshold at the widest noise bandwidth. It was speculated that this effect may
      be related to a decrease in sensitivity to modulation with continuous
      stimulation. In general, effects of gating appear to be small or absent for
      across-channel masking release in broadband modulated masking noise.

PMID- 8865644
TI  - Modulation discrimination interference and comodulation masking release as a
      function of the number and spectral placement of narrow-band noise modulators.
AB  - The discrimination of the depth of amplitude modulation (AM) of a target carrier
      can be adversely affected by the presence of other modulated carriers (flankers),
      an effect called modulation discrimination interference (MDI). Conversely, when
      the task is to detect a sinusoidal signal added to a modulated carrier of the
      same frequency, the presence of comodulated flankers (with the same modulation as
      the target carrier) can improve performance (comodulation masking release: CMR).
      This paper examines how CMR and MDI are influenced by the number and placement of
      the flankers. Flankers were spaced at 2-ERB intervals from the target, and their
      number was manipulated by adding flankers that were more remote from the target.
      Narrow-band noise (centered at 10 Hz) was used as the modulator for all carriers.
      In experiment 1, the MDI task required detection of a decrease in modulation
      depth (m) of the target from a reference value of 0.7. Unmodulated flankers did
      not affect thresholds. Modulated flankers (m = 0.15) produced MDI, which
      increased as more flankers were added. MDI was generally slightly greater for
      comodulated than for noncomodulated flankers. The CMR task required detection of
      a sinusoidal signal added (in 90 degrees phase) to the target carrier (m = 0.7).
      Unmodulated flankers or flankers that were noncomodulated with the target had no
      effect on threshold. Comodulated flankers (m = 0.7) gave CMR, which generally
      increased as more flankers were added. This effect was greater for flankers below
      the target frequency than for flankers above. Experiment 2 examined MDI using
      similar stimuli to experiment 1, except that the task was to detect an increase
      in m from a reference value of 0.1. Even unmodulated flankers elevated
      thresholds, and this effect increased as more flankers were added, especially on
      the high-frequency side of the target. Modulated flankers (m = 0.2) produced
      additional increases in threshold, and modulation thresholds generally increased
      as more flankers were added. However, the amount of MDI (the difference between
      thresholds with modulated and unmodulated flankers) did not vary systematically
      with the number of flankers and did not show consistent differences between
      comodulated and noncomodulated flankers. The results are interpreted in terms of
      the mechanisms underlying MDI and CMR, and especially perceptual grouping
      processes.

PMID- 8865645
TI  - Effects of phase and level on vowel identification: data and predictions based on
      a nonlinear basilar-membrane model.
AB  - This paper examines the role of component phase and level on vowel identification
      and interprets the results in terms of the shapes of the waveforms occurring at
      the outputs of the filters in a nonlinear basilar-membrane model. Four normally
      hearing subjects were asked to identify which of six possible vowel-like harmonic
      complexes was presented on each trial. The stimuli were complex tones containing
      the first 35 harmonics of a 100-Hz fundamental. All of the harmonics below 3000
      Hz were equal in amplitude except for three pairs of successive harmonics, at
      frequencies corresponding to the first three formants of six vowels, which were
      incremented in level relative to the background harmonics by 1, 2, 4, 8, and 16
      dB. The components in the harmonic complexes were added in four different
      starting phase relationships; cosine, random, Schroeder positive, and Schroeder
      negative. The stimuli were presented at three overall levels; 85, 65, and 45 dB
      SPL. Performance was similar for the random and Schroeder-negative phases and did
      not vary as a function of level. Performance for the cosine- and Schroeder
      positive-phase conditions was better than for the other two phase conditions, but
      decreased as the level was reduced. Performance for all four phase conditions was
      equivalent for the lowest level. The variation in performance as a function of
      level and component phase is explained in terms of the shapes of the temporal
      waveforms that would occur at the output of nonlinear "basilar-membrane filters"
      [H. W. Strube, J. Acoust. Soc. Am. 79, 1511-1518 (1986)], with asymmetric phase
      responses about the center frequency.

PMID- 8865646
TI  - Intensity discrimination as a function of stimulus level with electric
      stimulation.
AB  - Difference limens (DLs) for changes in electric current were measured from
      multiple electrodes in each of eight cochlear-implanted subjects. Stimuli were
      200-microseconds/phase biphasic pulse trains delivered at 125 Hz in 300-ms
      bursts. DLs were measured with an adaptive three-alternative forced-choice
      procedure. Fixed-level psychometric functions were also obtained in four subjects
      to validate the adaptive DLs. Relative intensity DLs, specified as Weber
      fractions in decibels [10 log (delta I/I)] for standards above absolute
      threshold, decreased as a power function of stimulus intensity relative to
      absolute threshold [delta I/I = beta (I/I0) alpha] in the same manner as Weber
      fractions for normal acoustic stimulation reported in previous studies. Exponents
      (alpha) of the power function for electric stimulation ranged from -0.4 to -3.2,
      on average, an order of magnitude larger than exponents for acoustic stimulation,
      which range from -0.07 to -0.11. Normalization of stimulus intensity to the
      dynamic range of hearing resulted in Weber functions with similar negative slopes
      for electric and acoustic stimulation, corresponding to an 8-dB average
      improvement in Weber fractions across the dynamic range. Sensitivity to intensity
      change ?10 log beta? varied from -0.42 to -13.5 dB compared to +0.60 to -3.34 dB
      for acoustic stimulation, but on average was better with electric stimulation
      than with acoustic stimulation. Psychometric functions for intensity
      discrimination yielded Weber fractions consistent with adaptive procedures and d'
      was a linear function of delta I. Variability among repeated Weber-fraction
      estimates was constant across dynamic range. Relatively constant Weber fractions
      across all or part of the dynamic range, observed in some subjects, were traced
      to the intensity resolution limits of individual implanted receiver/stimulators.
      DLs could not be accurately described by constant amplitude changes, expressed as
      a percentage of dynamic range ?delta A(% DR)?. Weber fractions from prelingually
      deafened subjects were no better or worse than those from postlingually deafened
      subjects. The cumulative number of discriminable intensity steps across the
      dynamic range of electric hearing ranged from as few as 6.6 to as many as 45.2.
      Physiologic factors that may determine important features of electric intensity
      discrimination are discussed in the context of a simple, qualitative, rate-based
      model. These factors include the lack of compressive cochlear preprocessing, the
      relative steepness of neural rate-intensity functions, and individual differences
      in patterns of neural survival.

PMID- 8865647
TI  - Evaluating the articulation index for auditory-visual consonant recognition.
AB  - Adequacy of the ANSI standard for calculating the articulation index (AI) [ANSI
      S3.5-1969 (R1986)] was evaluated by measuring auditory (A), visual (V), and
      auditory-visual (AV) consonant recognition under a variety of bandpass-filtered
      speech conditions. Contrary to ANSI predictions, filter conditions having the
      same auditory AI did not necessarily result in the same auditory-visual AI. Low
      frequency bands of speech tended to provide more benefit to AV consonant
      recognition than high-frequency bands. Analyses of the auditory error patterns
      produced by the different filter conditions showed a strong negative correlation
      between the degree of A and V redundancy and the amount of benefit obtained when
      A and V cues were combined. These data indicate that the ANSI auditory-visual AI
      procedure is inadequate for predicting AV consonant recognition performance under
      conditions of severe spectral shaping.

PMID- 8865648
TI  - Infant vocalizations in response to speech: vocal imitation and developmental
      change.
AB  - Infants' development of speech begins with a language-universal pattern of
      production that eventually becomes language specific. One mechanism contributing
      to this change is vocal imitation. The present study was undertaken to examine
      developmental change in infants' vocalizations in response to adults' vowels at
      12, 16, and 20 weeks of age and test for vocal imitation. Two methodological
      aspects of the experiment are noteworthy: (a) three different vowel stimuli (/a/,
      /i/, and /u/) were videotaped and presented to infants by machine so that the
      adult model could not artifactually influence infant utterances, and (b) infants'
      vocalizations were analyzed both physically, using computerized spectrographic
      techniques, and perceptually by trained phoneticians who transcribed the
      utterances. The spectrographic analyses revealed a developmental change in the
      production of vowels. Infants' vowel categories become more separated in vowel
      space from 12 to 20 weeks of age. Moreover, vocal imitation was documented,
      infants listening to a particular vowel produced vocalizations resembling that
      vowel. A hypothesis is advanced extending Kuhl's native language magnet (NLM)
      model to encompass infants' speech production. It is hypothesized that infants
      listening to ambient language store perceptually derived representations of the
      speech sounds they hear which in turn serve as targets for the production of
      speech utterances. NLM unifies previous findings on the effects of ambient
      language experience on infants' speech perception and the findings reported here
      that short-term laboratory experience with speech is sufficient to influence
      infants' speech production.

PMID- 8865649
TI  - Why stress position bias?
AB  - There is ample evidence in the literature that English and Dutch listeners tend
      to perceive stress on the word-initial syllable. This bias is most easily seen in
      the perception of (nonsense) words containing repetitions of identical syllables.
      In four experiments the possible causes of this bias are investigated. The
      results show that the bias disappears when (i) words are preceded by a spoken
      context, when (ii) the voice source is replaced by noise (whisper), or when (iii)
      the fundamental frequency level of the utterance as a whole is lowered. The data
      are best explained by assuming that the listener interprets the onset of voicing
      of an isolated word as a (silent) pitch rise from the bottom of the speaker's
      pitch range.

PMID- 8865650
TI  - The vowel-sequence illusion: intrasubject stability and intersubject agreement of
      syllabic forms.
AB  - Earlier studies have found that listeners presented with a loud and clear
      repeating sequence of brief steady-state vowels typically report hearing two
      voices with distinctly different timbres repeating different syllables that
      either are English words or occur in English words. One of the simultaneous
      voices is generally based upon frequencies below, and the other above, the
      "crossover frequency" at approximately 1500 Hz that divides normal speech into
      regions contributing equally to intelligibility. It has been hypothesized that
      the lack of linguistic content halts the processing of vowel sequences at the
      syllabic level, and that the spectral splitting corresponding to the concurrent
      voices reflects a mechanism for independent processing of different frequency
      regions that can lead to increased intelligibility under difficult listening
      conditions. The present study employed twelve randomly selected arrangements of
      the same six 70-ms vowels, and it was determined that: (1) individuals reported
      the same perceptual organizations the following week; (2) insertion of a brief
      silent gap between restatements of a sequence resulted in reports of similar (and
      occasionally identical) syllables by different listeners hearing the same
      sequence; and (3) when two listeners' responses differed, they could nevertheless
      identify the particular vowel sequences corresponding to each other's verbal
      forms. Spectrograms of vowel sequences were compared with time-aligned
      spectrograms of a speaker's synchronous production of the forms as they were
      being heard, and some common features of the acoustic patterns were noted. It is
      suggested that vowel sequences provide a reliable and useful tool for probing
      aspects of the perceptual organization of speech sounds that are normally
      obscured by additional linguistic processing.

PMID- 8865651
TI  - Fundamental frequency effects on thresholds for vowel formant discrimination.
AB  - The present experiments examined the effect of fundamental frequency (F0) on
      thresholds for the discrimination of formant frequency for male vowels.
      Thresholds for formant-frequency discrimination were obtained for six vowels with
      two fundamental frequencies: normal F0 (126 Hz) and low F0 (101 Hz). Four well
      trained subjects performed an adaptive tracking task under low stimulus
      uncertainty. Comparisons between the normal-F0 and the low-F0 conditions showed
      that formants were resolved more accurately for low F0. These thresholds for male
      vowels were compared to thresholds for female vowels previously reported by
      Kewley-Port and Watson [J. Acoust. Soc. Am. 95, 485-496 (1994)]. Analyses of the
      F0 sets demonstrated that formant thresholds were significantly degraded for
      increases both in formant frequency and in F0. A piece-wise linear function was
      fit to each of the three sets of delta F thresholds as a function of formant
      frequency. The shape of the three parallel functions was similar such that delta
      F was constant in the F1 region and increased with formant frequency in the F2
      region. The capability for humans to discriminate formant frequency may therefore
      be described as uniform in the F1 region (< 800 Hz) when represented as delta F
      and also uniform in the F2 region when represented as a ratio of delta F/F. A
      model of formant discrimination is proposed in which the effects of formant
      frequency are represented by the shape of an underlying piece-wise linear
      function. Increases in F0 significantly degrade overall discrimination
      independently from formant frequency.

PMID- 8865652
TI  - Spectral balance as an acoustic correlate of linguistic stress.
AB  - Although intensity has been reported as a reliable acoustical correlate of
      stress, it is generally considered a weak cue in the perception of linguistic
      stress. In natural speech stressed syllables are produced with more vocal effort.
      It is known that, if a speaker produces more vocal effort, higher frequencies
      increase more than lower frequencies. In this study, the effects of lexical
      stress on intensity are examined in the abstraction from the confounding accent
      variation. A production study was carried out in which ten speakers produced
      Dutch lexical and reiterant disyllabic minimal stress pairs spoken with and
      without an accent in a fixed carrier sentence. Duration, overall intensity,
      formant frequencies, and spectral levels in four contiguous frequency bands were
      measured. Results revealed that intensity differences as a function of stress are
      mainly located above 0.5 kHz, i.e., a change in spectral balance emphasizing
      higher frequencies for stressed vowels. Furthermore, we showed that the intensity
      differences in the higher regions are caused by an increase in physiological
      effort rather than by shifting formant frequencies due to stress. The potential
      of each acoustic correlate of stress to differentiate between initial- and final
      stressed words was examined by linear discriminant analysis. Duration proved the
      most reliable correlate of stress. Overall intensity and vowel quality are the
      poorest cues. Spectral balance, however, turned out to be a reliable cue, close
      in strength to duration.

PMID- 8865653
TI  - The effect of segment duration on the perceptual integration of nasals for adult
      and child speech.
AB  - It has been hypothesized that the acoustic properties within a temporal domain of
      10 to 30 ms of boundaries between speech sounds contain significant information
      on the phonetic features of segments, and that these cues are perceptually
      integrated by the auditory system [Stevens, Phonetic Linguistics: Essays in Honor
      of Peter Ladefoged (Academic, London, 1985)]. The purpose of the current research
      was to examine the effects of stimulus duration adjacent to speech sound
      boundaries on the perceptual integration of place of articulation of nasals
      before and after disruption of the abrupt changes in spectra between the murmur
      and transition. In experiment I, three children, aged 3, 5, and 7 years, and an
      adult female and male produced consonant-vowel (CV) syllables consisting of [m]
      and [n] in four vowel contexts, [i ae u a]. Approximately 25-ms segments of the
      murmur and vowel transition adjacent to the speech sound boundary were digitally
      removed from these productions. Intervals of silence ranging from 0 to 2000 ms,
      which can potentially perturb integration processes, were inserted between these
      segments. The stimuli were then presented to adult listeners for the
      identification of the nasal. The main findings revealed a consistent decline in
      identification with gap durations up to 150 ms across speakers and vowel context.
      However, the adult labial feature was resistant to perceptual change as a
      function of gap duration. This result appeared to relate to formant transition
      duration, and not to response bias. In experiment II, stimuli with durations
      shorter than those in experiment I were further analyzed for adult speakers. The
      main finding was a quantification of the acoustic segment duration needed for
      perceptual integration of the murmur and vowel transition. Across both
      experiments, the results reveal a decline in the identification of both alveolar
      and labial nasals within a time interval mediated by short-term auditory memory,
      and that the duration of the acoustic segment needed for perceptual integration
      is longer for [n] than [m].

PMID- 8865654
TI  - Noninvasive temperature estimation in tissue via ultrasound echo-shifts. Part I.
      Analytical model.
AB  - Temperature changes in tissue, caused by high-intensity focused ultrasound, cause
      time shifts in the echoes that traverse the heated tissue. These time shifts are
      caused by thermally induced changes in the distribution of the velocity of sound
      and by thermal expansion within the tissue. Our analytical model relates these
      shifts to changes in temperature distribution. It is proposed that these
      relationships can be used as a method for the noninvasive estimation of
      temperature within the tissue. The model shows that the echo shifts depend mostly
      on changes in the mean velocity along the acoustical path of the echoes and that
      no explicit information about the shape of the velocity distribution is required.
      The effects of the tissue thermal expansion are small in comparison, but may be
      significant under certain conditions. The theory, as well as numerical
      simulations, also predicts that the time shifts have an approximately linear
      behavior as a function of temperature. This suggests that an empirical linear
      delay-temperature relationship can be determined for temperature prediction. It
      is also shown that, alternatively, the distribution of temperature in the tissue
      can be estimated from the distribution of echo delays along the acoustical path.
      In the proposed system, low-level pulse echoes are sampled during brief periods
      when the high-intensity ultrasonic irradiation is off, and thus linear acoustic
      behavior is assumed. The possibility of nonlinear aftereffects and other
      disturbances limiting this approach is discussed.

PMID- 8865655
TI  - Noninvasive temperature estimation in tissue via ultrasound echo-shifts. Part II.
      In vitro study.
AB  - Time shifts in echo signals returning from a heated volume of tissue correlate
      well with the temperature changes. In this study the relationship between these
      time shifts (or delays) and the tissue temperature was investigated in excised
      muscle tissue (turkey breast) as a possible dosimetric method. Heat was induced
      by the repeated activation of a sharply focused high-intensity ultrasound beam.
      Pulse echoes were sent and received with a confocal diagnostic transducer during
      the brief periods when the high-intensity ultrasonic beam was inactive. The
      change in transit time between echoes collected at different temperatures was
      estimated using cross-correlation techniques. With spatial-peak temporal-peak
      intensities (ISPTP) of less than 950W/cm2, the delay versus temperature
      relationship was fit to a linear equation with highly reproducible coefficients.
      The results confirmed that for spatial-peak temperature increases of
      approximately 10 degrees C, temperature-dependent changes in velocity were the
      single most important factor determining the observed delay, and a linear
      approximation could produce accurate temperature estimations. Nonlinear phenomena
      that occurred during the high-intensity irradiation had no significant effect on
      the measured delay. At ISPTP of 1115-2698 W/cm2, the delay-temperature
      relationship showed a similar monotonically decreasing pattern, but as the
      temperature peaked its slope gradually increased. This may reflect the
      curvilinear nature of the velocity-temperature relationship, but it may also be
      related to irreversible tissue modifications and to the use of the spatial-peak
      temperature to experimentally characterize the temperature changes. Overall, the
      results were consistent with theoretical predictions and encourage further
      experimental work to validate other aspects of the technique.

PMID- 8865656
TI  - Onboard acoustic recording from diving northern elephant seals.
AB  - This study was the first phase in a long-term investigation of the importance of
      low-frequency sound in the aquatic life of northern elephant seals, Mirounga
      angustirostris. By attaching acoustic recording packages to the backs of six
      translocated juveniles, the aim was to determine the predominant frequencies and
      sound levels impinging on them, and whether they actively vocalize underwater on
      their return to their rookery at Ano Nuevo, California, from deep water in
      Monterey Bay. All packages contained a Sony digital audio tape recorder encased
      in an aluminum housing with an external hydrophone. Flow noise was minimized by
      potting the hydrophone in resin to the housing and orienting it posteriorly. The
      diving pattern of four seals was recorded with a separate time-depth recorder or
      a time-depth-velocity recorder. Good acoustic records were obtained from three
      seals. Flow noise was positively correlated with swim speed, but not so high as
      to mask most low-frequency sounds in the environment. Dominant frequencies of
      noise impinging on the seals were in the range 20-200 Hz. Transient signals
      recorded from the seals included snapping shrimp, cetacean vocalizations. boat
      noise, small explosive charges, and seal swim strokes, but no seal vocalizations
      were detected. During quiet intervals at the surface between dives, the acoustic
      record was dominated by respiration and signals that appeared to be heartbeats.
      This study demonstrates the feasibility of recording sounds from instruments
      attached to free-ranging seals, and in doing so, studying their behavioral and
      physiological response to fluctuations in ambient sounds.

PMID- 8865657
TI  - Comparing frequency-domain with time-domain solutions for a locally active
      nonlinear model of the cochlea.

PMID- 8865658
TI  - Sex differences in simultaneous masking with random-frequency maskers.

PMID- 8865659
TI  - Relation between the phonation threshold pressure and the prephonatory glottal
      width in a rectangular glottis.

PMID- 8865660
TI  - Satellite DNA of the red flour beetle Tribolium castaneum--comparative study of
      satellites from the genus Tribolium.
AB  - A highly abundant satellite DNA comprising 17% of the Tribolium castaneum
      (Insecta, Coleoptera) genome was cloned and sequenced. The satellite monomer is
      360 bp long, has a high A+T content of 73%, and lacks significant internal
      substructures. The sequence variability is 3.6%, essentially due to random
      distribution of single-point mutations. The satellite is evenly distributed in
      the regions of centromeric heterochromatin of all 20 chromosomes, as shown by
      fluorescent in situ hybridization. Comparison of T. castaneum satellite with
      those from three different but congeneric species reveals the highest sequence
      similarity of 47.1% with the satellite from the sibling species Tribolium
      freemani. The phylogenetic relationships among Tribolium species deduced from
      satellite sequence agree with those based on karyological, chemotaxonomic, and
      hybridization data. This indicates a parallel in the divergence of satellites and
      some genetic and cytogenetic characters. Despite low mutual sequence similarity,
      which makes them species-specific, Tribolium satellites have a common structural
      characteristic: a block of about 95% A+T content, 20 to 42 bp long, flanked at
      one side by an inverted repeat which can potentially form a thermodynamically
      stable dyad structure. Since similar structural features are found in centromeric
      DNA of Saccharomyces cerevisiae and Chironomus pallidivittatus, their possible
      importance in centromere function may be inferred.

PMID- 8865661
TI  - Geographic variation in human mitochondrial DNA control region sequence: the
      population history of Turkey and its relationship to the European populations.
AB  - The hypervariable segment I of the control region of the mtDNA (positions 16024
      16383) was amplified from hair roots by PCR and sequenced in 45 unrelated
      individuals from Anatolia (Asian Turkey). Forty different sequences were found,
      defined by 56 variable positions, of which only one involves a transversion. The
      neighbor-joining tree of Kimura's distance matrix for all sequences shows four
      main clusters. Cluster D was found to be the most statistically robust of the
      four, and all the sequences in it shared a mutation that is present only in
      European and West Asian populations. The variability in cluster D could have
      originated between 37,000 and 107,000 years ago. No branch is unexpectedly long,
      denoting the absence of sequences that diverged much before the others. The
      pairwise difference distribution is bell-shaped, in accordance with a population
      expansion occurring roughly 35,000 to 100,000 years ago. When compared to other
      Caucasoid populations through the pairwise difference distribution, there is a
      pattern from the Middle East (older expansion) to the various European
      populations, with Turkey in an intermediate position; when Turkish sequences are
      compared through a neighbor-joining tree on a genetic distance matrix of
      populations, this position is again evidenced. Although there is a very low level
      of genetic divergence among Caucasoid populations as shown by mtDNA control
      region sequences, a geographic pattern of genetic variation emerges, denoting a
      stepping-stone position of Turkey between the Middle East and Europe, which is in
      agreement with the hypothesis of a replacement of Neanderthals by modern humans,
      which could be related to the Upper Paleolithic cultural expansion.

PMID- 8865662
TI  - Sea urchin Hox genes: insights into the ancestral Hox cluster.
AB  - We describe the Hox cluster in the radially symmetric sea urchin and compare our
      findings to what is known from clusters in bilaterally symmetric animals. Several
      Hox genes from the direct-developing sea urchin Heliocidaris erythrogramma are
      described. CHEF gel analysis shows that the Hox genes are clustered on a < or =
      300 kilobase (kb) fragment of DNA, and only a single cluster is present, as in
      lower chordates and other nonvertebrate metazoans. Phylogenetic analyses of sea
      urchin, amphioxus, Drosophila, and selected vertebrate Hox genes confirm that the
      H. erythrogramma genes, and others previously cloned from other sea urchins,
      belong to anterior, central, and posterior groups. Despite their radial body plan
      and lack of cephalization, echinoderms retain at least one of the anterior group
      Hox genes, an orthologue of Hox3. The structure of the echinoderm Hox cluster
      suggests that the ancestral deuterostome had a Hox cluster more similar to the
      current chordate cluster than was expected Sea urchins have at least three Abd-B
      type genes, suggesting that Abd-B expansion began before the radiation of
      deuterostomes.

PMID- 8865663
TI  - Character congruence and phylogenetic signal in molecular and morphological data
      sets: a case study in the living Iguanas (Squamata, Iguanidae).
AB  - The lizard family Iguanidae comprises eight living genera distributed throughout
      the New and Old World, and includes several island endemics. We reconstruct
      phylogenetic relationships among these genera using 90 previously published
      morphological characters, to which we add a molecular (mtDNA sequence) data set
      that includes 742 nucleotides of the ND4 gene and the complete sequences of the
      histidine, serine, and leucine tRNAs (217 nucleotides). Trees were initially
      constructed separately from these three data sets, and then tested for
      significant conflict in topologies that would suggest the influence of different
      evolutionary processes. The three data sets were then combined, and a single tree
      was obtained from the total evidence that permitted identification of potential
      sources of character incongruence. Several additional analyses of the combined
      data sets were repeated with sequential deletion of successive classes of
      homoplastic characters, and we show that the same single tree topology is
      recovered in most cases. However, part of the tree structure collapses when the
      matrix of combined characters is completely purged of all homoplastic characters.
      We argue that this extreme results in an unacceptable loss of phylogenetic
      information, and we present a single phylogenetic hypothesis for all living
      genera of iguanas. We show that this hypothesis is significantly more
      parsimonious than either of two previously published trees, and we discuss the
      evolution and biogeography of the Iguanidae based on the preferred hypothesis.

PMID- 8865664
TI  - Lack of geographic variation in anonymous nuclear polymorphisms in the American
      oyster, Crassostrea virginica.
AB  - Comparing geographic variation of noncoding nuclear DNA polymorphisms, which
      presumably are neutral to natural selection, with geographic variation of
      allozymes is potentially a good way to detect the effects of selection on
      allozyme polymorphisms. A previous study of four anonymous nuclear markers in the
      American oyster, Crassostrea virginica, found dramatic differences in allele
      frequency between the Gulf of Mexico and the Atlantic Ocean. In contrast, 14
      allozyme polymorphisms were fairly uniform in frequency between the two areas.
      This led to the conclusion that all of the allozyme polymorphisms were kept
      uniform in frequency by balancing selection. To test the robustness of this
      pattern, six additional anonymous nuclear DNA polymorphisms were surveyed in
      oysters from Panacea, Fla, and Charleston, S.C. on the Gulf and Atlantic coasts,
      respectively. Unlike the previously studied DNA markers, the six DNA
      polymorphisms examined here show geographic variation that is not significantly
      greater than that of allozymes. The reason for the discrepancy between the two
      sets of DNA polymorphisms is unclear.

PMID- 8865665
TI  - Evolution of MHC class I loci in marsupials: characterization of sequences from
      koala (Phascolarctos cinereus)
AB  - We demonstrate that koala (Phascolarctos cinereus) MHC class I constitutes a
      variable multigene family. A total of nine partial exon 2 and 3 major
      histocompatibility complex (MHC) class I sequences are presented, including six
      sequences from at least three loci from one koala. Variation was detected by
      examination of sequences from a number of individuals and family groups. The
      koala is the second marsupial species characterized to date, and comparisons
      reveal approximately 80% similarity with sequences from the red necked wallaby
      (Macropus rufogriseus). The latter sequences represent at least two, and probably
      three, different loci. Phylogenetic analysis demonstrates that all koala
      sequences are more related to one another than they are to any of the wallaby
      loci. This indicates that the koala sequences are probably not orthologous to the
      wallaby genes, and thus represent a new class I gene family. In addition,
      marsupial gene families cluster away from human gene families, supporting a
      different origin of MHC genes for marsupials and eutherians.

PMID- 8865666
TI  - Origin of the Mesozoa inferred from 18S rRNA gene sequences.
AB  - The phylum Mesozoa comprises small, simply organized wormlike parasites of marine
      invertebrates and is composed of two classes, the Rhombozoa and the Orthonectida.
      The origin of Mesozoa is uncertain; they are classically considered either as
      degenerate turbellarians or as primitive multicellular animals related to
      ciliated protists. In order to precisely determine the phylogenetic position of
      this group we sequenced the complete 18S rRNA gene of one rhombozoid, Dicyema
      sp., and one orthonectid, Rhopalura ophiocomae. The sequence analysis shows that
      the Mesozoa branch early in the animal evolution, closely to nematodes and
      myxozoans. Our data indicate probably separate origins of rhombozoids and
      orthonectids, suggesting that their placement in the same phylum needs to be
      revised.

PMID- 8865667
TI  - High nucleotide sequence variation in a region of low recombination in Drosophila
      simulans is consistent with the background selection model.
AB  - We surveyed nucleotide sequence variation at glucose dehydrogenase (Gld), in a
      region of low recombination on chromosome 3R, from a population sample of
      Drosophila simulans. The levels of nucleotide variation were surprisingly high.
      There was no departure from the expectation of a neutral model for the level of
      polymorphism, indicating no evidence of a selective sweep in this region. There
      was a significant deficiency of singleton polymorphisms according to the Fu and
      Li test, although Tajima and Hudson, Kreitman, and Aguade (HKA) tests do not
      provide evidence of a significant elevation of variation due to balancing
      selection. Genetic map data for the D. simulans third chromosome were used to
      calculate expected values of pi for Gld under a current model of background
      selection, varying the values for the parameter sh (selection coefficient against
      deleterious mutations). We show that the recombinational landscape of D. simulans
      is sufficiently different from that of D. melanogaster that we expect higher
      variation under the background selection model, even when effective population
      sizes are assumed to be equal. The data for Gld were tested against the
      predictions using computer simulations of the distribution of the number of
      segregating sites conditioned on pi. Background selection alone can explain our
      observations as long as sh is larger than 0.005 and species-level effective
      population size is assumed to be several-fold larger than in D. melanogaster.
      Alternatively, the deleterious mutation rate may be smaller in D. simulans, or
      balancing selection may be acting nearby, thereby reducing the effect of
      background selection.

PMID- 8865669
TI  - Allelic diversity in alligator microsatellite loci is negatively correlated with
      GC content of flanking sequences and evolutionary conservation of PCR
      amplifiability.

PMID- 8865668
TI  - The phytochrome gene family in grasses (Poaceae): a phylogeny and evidence that
      grasses have a subset of the loci found in dicot angiosperms.
AB  - The phytochrome nuclear gene family encodes photoreceptor proteins that mediate
      developmental responses to red and far red light throughout the life of the
      plant. From studies of the dicot flowering plant Arabidopsis, the family has been
      modeled as comprising five loci, PHYA-PHYE. However, it has been shown recently
      that the Arabidopsis model may not completely represent some flowering plant
      groups because additional PHY loci related to PHYA and PHYB of Arabidopsis
      apparently have evolved independently several times in dicots, and monocot
      flowering plants may lack orthologs of PHYD and PHYE of Arabidopsis. Nonetheless,
      the phytochrome nucleotide data were informative in a study of organismal
      evolution because the loci occur as single copy sequences and appear to be
      evolving independently. We have continued our investigation of the phytochrome
      gene family in flowering plants by sampling extensively in the grass family. The
      phytochrome nuclear DNA data were cladistically analyzed to address the following
      questions: (1) Are the data consistent with a pattern of differential
      distribution of phytochrome genes among monocots and higher dicots, with homologs
      of PHYA, B, C, D, and E present in higher dicots, but of just PHYA, B, and C in
      monocots, and (2) what phylogenetic pattern within Poaceae do they reveal?
      Results of these analyses, and of Southern blot experiments, are consistent with
      the observation that the phytochrome gene family in grasses comprises the same
      subset of loci detected in other monocots. Furthermore, for studies of organismal
      phylogeny in the grass family, the data are shown to provide significant support
      for relationships that are just weakly resolved by other data sets.

PMID- 8865670
TI  - Hearing protection works!

PMID- 8865671
TI  - The health care worker plague.

PMID- 8865672
TI  - The dangers of chemical weapons.

PMID- 8865673
TI  - Safe lead abatement at a major food processing plant.

PMID- 8865674
TI  - Stimulus uncertainty and speaker normalization processes in the perception of
      nasal consonants.
AB  - Previous research has noted a reduction in perceptual identification performance
      when the speaker varies from stimulus to stimulus and has interpreted this
      finding as an effect of a normalization process that compensates for variability
      in the physical content of the speech signal. The purpose of the present
      investigation was to examine whether the physical variability introduced by this
      experimental design can result in general stimulus uncertainty effects that
      extend beyond the realm of traditional delineations of normalization processes.
      The stimuli were short segments taken from nasal consonant + vowel syllables
      produced by 1 male adult, 1 female adult, and 2 children. Segments of 25 and 50
      ms duration were edited from the nasal murmur and the onset of the vowel. The
      stimuli were ordered according to four variability conditions and presented to
      listeners for place of articulation identification. The results showed that
      identification was significantly reduced when variability affected either speaker
      identity or segment type. Further analyses revealed that segment variability
      impaired perception of all segment types approximately equally, but that the 50
      ms vowel segments were selectively spared in the speaker variability condition.
      These findings indicate that general uncertainty effects should be considered in
      speech perception experiments, and that dynamic properties of speech are
      particularly important in the perceptual compensation for speaker variability.

PMID- 8865675
TI  - Acoustic correlates of stress in Thai.
AB  - Acoustic correlates of stress [duration, fundamental frequency (Fo), and
      intensity] were investigated in a language (Thai) in which both duration and Fo
      are employed to signal lexical contrasts. Stimuli consisted of 25 pairs of
      segmentally/tonally identical, syntactically ambiguous sentences. The first
      member of each sentence pair contained a two-syllable noun-verb sequence
      exhibiting a strong-strong (--) stress pattern, the second member a two-syllable
      noun compound exhibiting a weak-strong (--) stress pattern. Measures were taken
      of five prosodic dimensions of the rhyme portion of the target syllable:
      duration, average Fo, Fo standard deviation, average intensity, and intensity
      standard deviation. Results of linear regression indicated that duration is the
      predominant cue in signaling the distinction between stressed and unstressed
      syllables in Thai. Discriminant analysis showed a stress classification accuracy
      rate of over 99%. Findings are discussed in relation to the varying roles that
      Fo, intensity, and duration have in different languages given their phonological
      structure.

PMID- 8865676
TI  - City air pollution of polycyclic aromatic hydrocarbons and other mutagens:
      occurrence, sources and health effects.
AB  - The presence of polycyclic aromatic hydrocarbons (PAH), mutagens and other air
      pollutants was investigated in a busy street in central Copenhagen and in a park
      area adjacent to the street. The winter concentration of benzo(a)pyrene was 4.4
      +/- 1.2 ng/m3 in the street air and 1.4 +/- 0.6 ng/m3 in the city park. The
      atmospheric concentrations of PAH decreased in the order of: street > city
      background air approximately suburbs > village > open land. The traffic
      contribution of PAH to street air was estimated to be 90% on working days and 60%
      during weekends and its contribution to city background air was estimated to be
      40%. Four different approaches to evaluate the health effects are discussed. The
      direct effect of PAH air pollution, and other mutagens, is considered to be a
      maximum of five lung cancer cases each year out of one million people.

PMID- 8865677
TI  - Exposure of Danish children to traffic exhaust fumes.
AB  - This exposure study addresses the validity of the exposure assessment method of
      an epidemiological study of traffic-related air pollution and childhood cancer.
      In particular, this paper concerns the question of whether the concentration of
      nitrogen dioxide (NO2) outside the front door is a valid marker of the exposure
      of the child living at the address. The study includes 100 children living on
      streets with dense traffic in central parts of Copenhagen and 100 children living
      in rural areas. Preliminary results, based on 25% of the study subjects, suggest
      that both the outdoor NO2-concentration and the exposure of the children are two
      to three times higher in Copenhagen than in the rural districts. Moreover, the
      results suggest that the NO2-concentration outside the front door is a poor
      marker of the exposure of the children in Copenhagen, but a marker of some
      relevance for the exposure of the children in rural districts. The preliminary
      results must be treated with caution, as among other things, the analysis did not
      consider seasonal changes and indoor NO2-sources such as passive smoking,
      candles, and gas appliances.

PMID- 8865678
TI  - Verification of expected trends in urban traffic NOx emissions from long-term
      measurements of ambient NO2 concentrations in urban air.
AB  - Data from long-term measurements of ambient NO2 concentrations at roof level in
      15 Swedish cities have been used to verify expected trends in urban traffic NOx
      emissions, resulting mainly from the growth in the number of threeway catalyst
      (TWC) cars in Sweden since the mid 1980s. The result show that, with few
      exceptions, all cities exhibit a highly significant downward trend in ambient NO2
      concentration since the winter season 1986/1987, as regards both winter season
      averages and 98th percentiles of daily averages, with an average decrease in both
      cases of approximately 30% through the winter season 1993/1994. The same trend is
      also observed when meteorological variations between years are taken into
      account. Corrections for NO2 in background air yield an even stronger downward
      trend, or an average 40% decrease for the study period. Simultaneously, rough
      calculations indicate a 30% decrease in urban traffic NOx emissions during the
      study period. The conclusions are that, since emission calculations always
      involve a high degree of uncertainty, use of data from long-term measurements of
      NO2 concentrations in urban air can be very helpful in establishing real-world
      trends for urban traffic NOx emissions, as soon as NOx-levels are low enough for
      the NO+ozone reaction to become 'NOx-limited'.

PMID- 8865679
TI  - Turbulence effects upon the NO2/NO conversion in the vicinity of an urban area.
AB  - The dispersion and chemical transformation of nitrogen oxides have been studied
      in an urban atmosphere. In this work, nitric oxide is considered as being emitted
      from the ground. It is mixed with ambient ozone with which it reacts to produce
      nitrogen dioxide. Numerical integration of the transport equation of each species
      is carried out in the boundary layer, allowing for the effects of dipersion,
      macro- and micromixing and chemistry. The results show that the influence of
      turbulence on chemical reactions is important close to the emission zone. It is
      also found that the NO/NO2 conversion is low in this region and that it grows
      with increasing distances.

PMID- 8865680
TI  - Determination of PAH in airborne particulate: comparison between off-line
      sampling techniques and an automatic analyser based on a photoelectric aerosol
      sensor.
AB  - The automatic analyser is based on a photoelectric aerosol sensor, with
      continuous sampling and an on-line detection system. Traditional sampling
      monitoring systems consist of collecting airborne particulate on filters; the
      sample is then extracted, purified and analysed. It is possible to identify each
      compound and to determine its relative abundance in the total particulate matter,
      on the other hand, this method requires great complexity of analysis. Continuous
      monitoring systems allow getting quicker results to compare with threshold
      levels. It is also possible to obtain an easier correlation with factors such as
      traffic flows or meteorological conditions. However, such systems cannot quantify
      single compounds, and data are expressed as total PAH. The comparison between the
      results shows a satisfactory linearity between the data obtained with the two
      methods. The difference of about one order of magnitude between the data obtained
      with photoelectric aerosol sensor (PAS) system and the sum of the concentrations
      of selected PAHs determined with off-line methods can be explained with the
      different selectivity of the two methods employed. This work has been developed
      in Aosta, the administrative centre of the Aosta Valley district.

PMID- 8865681
TI  - [Cyclic alteration in atheroma plaque morphology observed by intracoronary
      ultrasound: initiation mechanism of acute myocardial infarction].
AB  - Rupture of plaque is an important factor in the initiation of acute myocardial
      infarction. Plaque rupture is related to stress distribution in atheroma, but
      morphological alteration in coronary atheroma plaque in vivo is little
      understood. Atheroma plaque was observed during the cardiac cycle using 3.5 or
      2.8 F, 30 MHz intracoronary ultrasound (ICUS) in seven patients with coronary
      artery disease. Coronary ostial pressure (P) measurements were simultaneously
      performed. Seven of the eccentric stenotic sites were analyzed. Intima-medial
      thickness (Th) and regional radius of curvature (R) at the middle and lateral
      portions of the atheroma were measured. Delta Th and % delta Th were calculated
      from change in thickness from end-diastole to peak systole. These parameters of
      the middle portion were compared with those of the lateral portion. The lateral %
      delta Th was 20.1 +/- 13.6% (delta Th 0.13 +/- 0.08 mm; 0.69 to 0.56 mm), and was
      significantly greater than the middle % delta Th [5.8 +/- 6.6% (delta Th 0.06 +/-
      0.08 mm; 1.24 to 1.18 mm), p < 0.05]. Regional radius of curvature did not
      significantly differ. Wall stress calculated as P x R/Th was greater at the
      lateral portion (peak systole 3.7 x 10(5) dynes/cm2, end-diastole 1.9 x 10(5)
      dynes/cm2) than at the middle portion (peak systole 1.4 x 10(5) dynes/cm2, end
      diastole 0.9 x 10(5) dynes/cm2). The change in stress from end-diastole to peak
      systole at the lateral portion was significantly greater (1.8 x 10(5) dynes/cm2)
      than that at the middle portion (0.5 x 10(5) dynes/cm2). The change in stress
      during the cardiac cycle, caused by the increase in intracoronary pressure, was
      greater at the lateral than at the middle of the plaque. This imbalanced
      distribution of stress may result in greater thinning of plaque at the lateral
      portion. Therefore, the distortion of plaque may be a mechanism for atheroma
      rupture at the lateral portion.

PMID- 8865682
TI  - [Evaluation of coronary arterial remodeling using intravascular ultrasound
      imaging].
AB  - Previous pathological studies demonstrated that the atherosclerotic coronary
      artery enlarges in response to developing atherosclerotic plaque. To clarify this
      phenomenon of coronary arterial remodeling, 24 segments of the left anterior
      descending artery were studied with intravascular ultrasound imaging. The luminal
      area and vessel area (area bounded by the echolucent zone) were measured by
      planimetry, and the percentage plaque area was calculated. Vessel area was
      correlated with plaque area (y = 12.3 + 0.72, r = 0.54, p < 0.001). When the 24
      coronary segments were divided into two categories according to the percentage
      plaque area, there was no correlation between plaque area and lumen area in the
      coronary segment with less than 40% plaque area (n = 14, r = 0.20, p = NS) or
      less than 30% plaque area (n = 9, r = 0.18, p = NS). However, there was a
      correlation between plaque area and lumen area in the coronary segments with
      greater than 40% plaque area (n = 10, y = 22.1-0.27x, r = -0.82, p < 0.01). The
      correlation was somewhat better in cases with greater than 30% plaque area (n =
      15, y = 22.5-0.28x, r = -0.89, p < 0.0001). Intravascular ultrasound imaging
      demonstrates the phenomenon of coronary arterial remodeling in vivo, which
      indicates that human coronary artery enlarges in response to increasing plaque
      area until the plaque occupies 30% of the vessel area. However, if the plaque
      occupies more than 30%, an increase in plaque area leads to a decrease in lumen
      area. Therefore, the phenomenon of coronary arterial remodeling is a compensatory
      mechanism to prevent luminal narrowing in the early stage of human coronary
      atherosclerosis.

PMID- 8865683
TI  - [Comparison of thrombolytic therapy and direct percutaneous transluminal coronary
      angioplasty for acute myocardial infarction: prospective multicenter trial at 16
      clinical centers in Ibaraki prefecture TUGMI. Tsukuba University Group for
      Myocardial Infarction].
AB  - The efficacies of direct percutaneous transluminal coronary angioplasty (PTCA)
      and thrombolysis for the treatment of acute myocardial infarction were
      investigated in 80 patients treated within 12 hours of the onset of myocardial
      infarction by either PTCA (39 patients) or thrombolytic therapy (41 patients)
      followed by conservative care. The therapeutic approach was selected according to
      the treatment strategy at each of the 16 participating centers before the
      admission of the patients. The two treatment groups were closely matched in
      clinical characteristics except for the history of hypertension which occurred
      more in the thrombolysis group (22/39 vs 12/41, p = 0.026). The mean time before
      starting reperfusion therapy from the onset of symptoms was shorter in the
      thrombolysis group (2.3 +/- 1.5 vs 5.3 +/- 5.7 hours, p = 0.0001). Chest pain
      resolved more quickly in the PTCA group. Serial changes in the mean numbers of
      abnormal Q waves and mean values of the sum of elevated ST-segments on the
      electrocardiograms were similar in both groups. Serial changes of wall motion
      abnormality index on echocardiograms were similar in both groups. Coronary
      angiography after 4 weeks showed the thrombolysis group had greater residual
      luminal stenosis in the infarct-related artery. Left ventriculography after 4
      weeks showed the PTCA group had better mean ejection fraction (68.1 +/- 11.2% vs
      58.7 +/- 14.2%, p = 0.0263). Death (3/39 vs 1/41) and cardiac events (6/39 vs
      6/41) after 4 weeks were similar in both groups. There was no significant
      difference in death and cardiac events between these two groups. However, the
      PTCA group had less severe residual luminal stenosis in the infarct-related
      artery and better left ventricular function after 4 weeks than the thrombolysis
      group.

PMID- 8865684
TI  - [Changes in plasma level of brain natriuretic peptide during exercise in recovery
      phase of myocardial infarction and the clinical significance].
AB  - Brain natriuretic peptide (BNP) plasma levels increase in patients with
      myocardial infarction and may reflect the degree of left ventricular dysfunction.
      The changes in plasma level of BNP during exercise in the recovery phase and the
      clinical significance were investigated in 60 patients (55 men and 5 women; mean
      age 62.3 +/- 9.8 years) with initial acute infarction. Cardiopulmonary exercise
      testing was performed with a treadmill using the ramp protocol in 60 patients in
      the first month and 46 in the third month after the onset of the disease. Blood
      samples for measuring BNP and atrial natriuretic peptide (ANP) were obtained in
      the resting control state and immediately after peak exercise. Plasma BNP in the
      first month had a significant negative correlation with anaerobic threshold (AT)
      and peak oxygen uptake (peak VO2), and the serial change in plasma BNP from the
      first to third month had a significant negative correlation with the serial
      change of AT (peak: r = -0.35, p < 0.05) and peak VO2 (rest: r = -0.35, p < 0.05;
      peak: r = -0.45, p < 0.01). The serial change of plasma ANP had no relationships
      with the serial change of AT or peak VO2. Because the serial change ratio of
      plasma BNP reflects the serial change of exercise tolerance in the recovery phase
      of myocardial infarction, we conclude that the serial measurement of plasma BNP
      level is a useful non-invasive parameter for predicting latent heart failure in
      patients with myocardial infarction.

PMID- 8865685
TI  - [Myocardial sympathetic activity and characteristics in hypertrophic
      cardiomyopathy: comparison with hypertensive hypertrophy].
AB  - The characteristics of myocardial sympathetic activity were studied using
      myocardial imaging with I-123-metaiodobenzylguanidine (MIBG) in 16 patients with
      hypertrophic cardiomyopathy (HCM), 12 patients with essential hypertension and
      left ventricular hypertrophy (HT) and 10 normal subjects. Myocardial imaging with
      MIBG and thallium-201 (T1) was performed at rest on a separate day. The index of
      myocardial MIBG uptake, "uptake ratio", was calculated from the percentage uptake
      of MIBG and T1. Reduction of myocardial MIBG during 3 hours (percentage washout)
      was also calculated. The extent of the defect was quantitatively assessed (defect
      score) from the bull's eye map. Global "uptake ratio" of the delayed image
      decreased in the order of normal subjects, patients with HT and those with HCM (p
      < 0.01). Defects in MIBG images were observed in all patients with HCM and 92% in
      those with HT. The defects were located in the inferior and lateral segments in
      patients with HT, but around the entire left ventricle in patients with HCM. Both
      groups had smaller regional "uptake ratio" than normal subjects, but HT and HCM
      demonstrated different behaviors: reduced in the inferior and lateral segments as
      compared with other segments in HT, but distributed equally in all segments in
      HCM. In patients with HCM, percentage washout was significantly accelerated in
      comparison with patients with HT and normal subjects in both global and regional
      analyses, but there was no difference between the latter two groups. Disturbance
      of myocardial sympathetic activity observed in patients with HCM by MIBG uptake
      and washout differed from that caused by HT.

PMID- 8865686
TI  - [Aortic inner surface morphology in aortic disease by three-dimensional
      transesophageal echocardiography].
AB  - Aortic inner surface morphology in various pathologies was investigated using
      three-dimensional (3D) transesophageal echocardiography to clarify the
      feasibility and limitations for clinical application. Transesophageal
      echocardiography was performed in 16 patients with aortic disease (12 aortic
      dissection, 4 aortic sclerosis) and 5 with normal aorta. The transesophageal
      transverse view of the descending aorta was taken every 2 mm by manually
      withdrawing the probe. Each image was recorded using VTR during one heart beat,
      then stored in the memory of a personal computer as a data base for the
      subsequent 3D reconstruction. The aortic inner surface was displayed using
      distance and gradient shading. Three-dimensional reconstruction images were
      obtained in all patients. The aortic inner surface was reconstructed as a wall
      with ringed protrusion in patients with normal aorta and a rugged wall with
      various sized protrusions in patients with atherosclerotic plaques by 3D
      transesophageal echocardiography. However, it was impossible to differentiate
      calcified lesions from non-calcified areas of plaques. In aortic dissection, 3D
      reconstruction provided information regarding the spatial anatomy of the
      dissection in 10 of 12 patients, accurate shape and location of the intimal tears
      in 3 of 5 patients, and movement of the intimal flap in 9 of 12 patients.
      However, reconstruction of the false lumen failed in two patients who had false
      lumens filled with spontaneous contrast echo. Three-dimensional transesophageal
      echocardiography is potentially useful for estimating the inner surface
      morphology and spatial extent and actual location of the aortic abnormalities,
      but there are limitations in evaluating tissue characterization and
      reconstructing the lumen with spontaneous contrast echo.

PMID- 8865687
TI  - [Cardiomyoplasty effectiveness: review of the mechanism].
AB  - The effectiveness of cardiomyoplasty on cardiac function is discussed, and the
      four mechanisms proposed to explain cardiomyoplasty effectiveness are reviewed.
      The first such mechanism, termed the squeezing effect, suggests that skeletal
      muscle wrapped around the heart squeezes the heart in the same way as cardiac
      massage, resulting in direct improvement in cardiac function. Hemodynamic
      improvement is rarely detectable, but significant subjective improvement is
      commonly seen clinically. The second mechanism, termed the sparing effect,
      suggests that even if cardiac performance remains unchanged after
      cardiomyoplasty, contraction of the wrapped lattisimus dorsi muscle causes an
      increase in the slope of the end-systolic pressure-volume relationship, and a
      reduction in left ventricular wall stress. Myocardial oxygen consumption is
      thereby reduced. The third mechanism, called the girdling effect, suggests that
      cardiomyoplasty may act like an elastic girdle around the heart to prevent
      enlargement of the failing heart. The fourth mechanism, called the collateral
      effect, suggests that, when applied to the ischemic heart, cardiomyoplasty
      increases collateral blood flow to the myocardium, thereby benefiting cardiac
      function. However, the existence of unknown mechanisms is suggested by two
      phenomena that cannot be explained by these four mechanisms alone.
      Cardiomyoplasty was introduced as a method of direct cardiac assistance. However,
      it now appears that the relatively passive role of cardiomyoplasty in oxygen
      consumption saving and ventricular enlargement prevention may be of great
      importance.

PMID- 8865688
TI  - [A 63-year-old man complaining of shortness of breath after coronary bypass
      surgery].

PMID- 8865689
TI  - [Gamma knife radiosurgery for acoustic neurinoma: history and present situation].

PMID- 8865690
TI  - [Stereotactic radiosurgery for the treatment of brain metastases].

PMID- 8865691
TI  - [Gamma radiosurgery for malignant tumors].

PMID- 8865692
TI  - [Radiosurgery of cerebral arteriovenous malformations: an update].

PMID- 8865693
TI  - [Stereotactic multiple arc radiotherapy].

PMID- 8865694
TI  - [Dystonia preceding dopa-responsive parkinsonism--heterogeneous clinical
      features].
AB  - We report six patients with dystonia-parkinsonism syndrome having a common
      characteristic clinical course of dystonia with subsequent development of
      levodopa-responsive parkinsonism. Various types of dystonic symptoms were
      observed such as hemidystonia, torticollis, axial dystonia, focal dystonia, or
      cranial dystonia (Meige's syndrome). Intervals between the onset of dystonia and
      that of parkinsonism varied from one year to about 20 years or the more. Levodopa
      and a dopamine against had inconstant effects on their dystonic symptoms except
      for the torticollis of the patients; on the other hand, parkinsonism were well
      relieved by levodopa in all of them. Dystonic symptoms showed heterogeneous drug
      effects. Carbamazepine had a beneficial effect on hemidystonia in a patient with
      hemidystonia-parkinsonism. In a patient with an unilateral hand cramp-ipsilateral
      parkinsonism, the focal dystonic symptom was evoked by cigarette smoking. Meige's
      syndrome became worse by the administration of levodopa. In contrast, in a
      patient with younger onset toriticollis-parkinsonism, both symptoms were fully
      relieved by levodopa. From the clinical and pharmacological points of views, this
      type of dystonia-parkinsonism, characterized by dystonia with later development
      of dopa-responsive parkinsonism, is a syndrome showing heterogeneous dopa
      response, and it remains uncertain, at the present, that whether or not patients
      reported here share the same clinicopathological background such as striatal
      dopamine deficiency.

PMID- 8865695
TI  - [Atlantoaxial dislocation with ventilatory insufficiency--report of two cases].
AB  - We performed electromyography and polysomnography in two cases of atlantoaxial
      dislocation with ventilatory insufficiency to determine the patients' respiratory
      patterns. The results showed that hypertrophic sternocleidomastoid muscles (SCMs)
      played an important part in their respiration. The diaphragm and intercostal
      muscles did not display marked electromyographic (EMG) activity, but the SCMs
      showed a great deal of phasic inspiratory activity during the daytime that
      decreased or disappeared during sleep. A 6-year-old boy with atlantoaxial
      dislocation related to spinal abnormalities was chiefly dependent on the SCMs for
      respiration and required mechanical ventilation when a sleep because the SCMs
      were completely inactive. A 4-year-old girl with atlantoaxial dislocation as the
      result of an automobile accident was partially dependent on the SCMs. She had no
      trouble breathing during the daytime, but polysomnography recordings showed
      recurrent hypopnea and desaturation during the night synchronous with decreased
      EMG activity of the SCMs. She also required mechanical ventilation to improve her
      long-term prognosis. Polysomnography should be performed in severe cases of
      atlantoaxial dislocation with respiratory failure in addition to routine
      respiratory function tests.

PMID- 8865696
TI  - [Changes in arterial ketone body ratio (AKBR) in subarachnoid hemorrhage
      patients].
AB  - The arterial ketone body ratio (AKBR) is considered an accurate index of the
      functional reserve of the liver, and its validity has been confirmed in the field
      of abdominal surgery. We found low AKBR values subarachnoid hemorrhage patients
      and discuss the clinical significance of this finding in this paper. Twenty-eight
      patients with subarachnoid hemorrhage treated at our institution were included in
      this study. Their ages ranged from 26 to 81 years old (average: 61.5 years).
      According to the WFNS classification 12 cases were grade I, II, or III, and 16
      were grade or IV V. Surgical clipping was performed in 23 of these cases, within
      2 days after symptoms of subarachnoid hemorrhage appeared. There were eight cases
      of symptomatic vasospasm and three cases of re-ruptured aneurysm. Outcome was
      classified according to the Glasgow Outcome Scale (GOS) as: good recovery (GR),
      moderately disabled (MD), severely disabled (SD), vegitative survival (VS), and
      dead (D). Using these criteria, the outcome of these patients was as follows: GR
      or MD in 10 cases, SD or VS in 8 case, and D in 10 cases. Ten healthy adults were
      chosen as controls. We collected arterial blood samples on days 1, 2, 3, 7, 10
      and 14 after the onset of symptoms (day 0) and measured the following: 1, beta
      hydroxybutyrate; 2, acetoacetate; 3, epinephrine; and 4, norepinephrine. On day 0
      total ketone body levels were higher (165.6 +/- 119.9 mumol/l), and AKBR values
      (0.65 +/- 0.24) were significantly lower than in the control group (2.50 +/-
      1.09) (p < 0.001), while both epinephrine and norepinephrine levels were
      significantly higher, 506.5 +/- 200.3 pg/ml and 899.5 +/- 221.4 pg/ml,
      respectively. The AKBR value was 0.90 +/- 0.27 on day 1, 1.11 +/- 0.4 0 on day 2,
      and increased thereafter. The average AKBR value exceeded 1.0 on day 2 in the ten
      GR and MD cases. In the SD and PVS cases, however, it exceeded 1.0 on day 3, but
      in the D patients it never exceeded 1.0 and instead was significantly lower. AKBR
      values are known to decrease not only in hepatic failure, but in cases in which
      the liver energy charge is reduced, such as shock and hypoxemia, but no
      investigations have ever been performed to determine whether AKBR is altered in
      cerebrovascular disease. In this study, we found that AKBR values were lower in
      subarachnoid hemorrhage, presumably due to the reduced hepatic blood flow caused
      by the increased levels of epinephrine and norepinephrine. In addition, our
      findings suggested that the fluctuations in AKBR values were correlated with the
      outcome of subarachnoid hemorrhage patients.

PMID- 8865697
TI  - [Hypoplasia of the left internal carotid artery associated with anterior
      communicating aneurysm, intercarotid anastomosis and left rete carotidis].
AB  - Hypoplasia of the internal carotid artery with cerebral aneurysm is extremely
      rare. The authors report a case of hypoplasia of the left internal carotid artery
      associated with anterior communicating aneurysm, intercarotid anastomosis and
      left rete carotidis. A 45-year-old man was admitted to Minamata Municipal
      Hospital because of severe headache and disturbance of consciousness. CT scan
      showed subarachnoid hemorrhage with intracerebral hematoma. Right carotid
      angiogram showed the anterior communicating aneurysm arising from the right A1-A2
      corner and intercarotid anastomosis on the cavernous portion. The distal part
      from the C4 portion of the left internal carotid artery was revealed through
      these anastomotic vessels. Left carotid angiogram showed hypoplasia of the left
      internal carotid artery and unusual tortuous collateral vessels arising from the
      left internal maxillary artery, ascending pharyngeal artery and its branches to
      the left internal carotid artery. These collateral vessels are called "rete
      carotidis" or "rete mirabile caroticum." Both the intercarotid anastomosis and
      rete carotidis are unusual anastomotic vessels and are considered not to appear
      during normal development of the cranial circulation in humans. CT scan with
      skull base bone target image showed hypoplasia of the left carotid canal. In this
      case, the change in cranial circulation due to hypoplasia of the internal carotid
      artery was considered one of the main factors in the development of these unusual
      anastomotic vessels and cerebral aneurysm.

PMID- 8865699
TI  - [A case of vascular parkinsonism with unsuspected multiple cerebral hemorrhage
      detected by MRI].

PMID- 8865698
TI  - [Familial amyloidotic polyneuropathy with a transthyretin variant (Val30-->Leu)].
AB  - We report a Japanese woman with familial amyloidotic polyneuropathy (FAP) with a
      transthyretin variant that substituted leucine for valine at position 30. Family
      history was not informative. She had initially suffered from repeated petechiae
      in the eyelids at the age of 51. Two years later, dysesthesia in the lower
      extremities appeared. Distal muscle weakness and sensory disturbance gradually
      developed. Autonomic dysfunction emerged and vomiting and orthostatic hypotension
      were marked in the late stage of her illness. Because of renal failure, she died
      at the age of 54. At autopsy, amyloid deposits were prominent in peripheral
      nerves including autonomic nerves, heart, blood vessels, gastrointestinal tract,
      kidneys, and bladder. In the nervous system, we found amyloid deposits in
      anterior roots, posterior roots, posterior root ganglions, peripheral nerves, and
      sympathetic ganglions. Cardiac weight was increased (595 g) with conspicuous
      amyloid deposits in the myocardium. The kidneys showed massive deposition of
      amyloid in the glomeruli and vascular walls. Amyloid accumulated moderately in
      tongue, submandibular gland, gallbladder, spleen, and pancreas, and slightly in
      the thyroid gland, lung, liver, and adrenal gland. No amyloid deposits were seen
      in the CNS with the exception of perivascular deposits in the choroid plexus.

PMID- 8865700
TI  - [Amrinone (50 micrograms.kg-1.min-1) does not impair regional myocardial tissue
      metabolism during the 40%-decrease of left anterior descending coronary flow].
AB  - We investigated the effects of amrinone on metabolism of regional myocardial
      tissue during the 40%-decrease of left anterior descending coronary (LAD) flow in
      anesthetized dogs. Fourteen adult mongrel dogs weighing 15.4 +/- 5.1 kg were
      anesthetized with 0.5% isoflurane in 50% oxygen and ventilated mechanically to
      maintain normocapnia. After thoracotomy, regional myocardial tissue PO2 was
      measured using a monopolar polarographic needle electrode inserted in the
      myocardium. Electromagnetic blood flow probes were placed around LAD and
      circumflex artery. A 23-gauge catheter was inserted into a coronary vein which
      runs along LAD to obtain coronary venous blood for measuring oxygen content,
      lactate and pyruvate. A variable constrictor was placed distal to the flow-probe.
      After decreasing LAD flow for 40%, cardiac index (CI) decreased. Systemic venous
      resistance was decreased and CI was increased by amrinone (50 micrograms.kg-1.min
      1) infusion. Myocardial tissue oxygen tension, venous lactate, lactate
      extraction, lactate-pyruvate ratio and excess lactate were all unchanged by
      amrinone. In conclusion, amrinone does not impair myocardial aerobic metabolism
      and increases CI under the stenosis of coronary artery.

PMID- 8865701
TI  - [Comparison of cerebral oxygen metabolism during normothermic versus moderate
      hypothermic cardiopulmonary bypass].
AB  - We compared the effects of normothermic (NCPB, N = 5) and moderate hypothermic
      (HCPB, (N = 5) cardiopulmonary bypass on cerebral oxygen metabolism in patients
      undergoing coronary artery bypass grafting. For monitoring of cerebral
      oxygenation, we used jugular venous oxyhemoglobin saturation (SjVO2) and near
      infrared spectroscopy (NIR). In NCPB group, although SjVO2 decreased temporally
      at the start of cardiopulmonary bypass, it became stabilized above 50% during the
      rest of cardiopulmonary bypass. In HCPB group, on the contrary, oxyhemoglobin
      measured by NIR showed maximum decrease during rewarming under cardiopulmonary
      bypass. Furthermore, SjVO2 decreased under 50% at the end of cardiopulmonary
      bypass (3/5 cases). We consider that NCPB is a useful technique for preventing
      cerebral hypoxia, if the decrease of SjVO2 during the early period of
      cardiopulmonary bypass is avoidable. Lastly, we also advocate that both SjVO2 and
      NIR are useful monitoring systems for continuous evaluation of cerebral oxygen
      metabolism during cardiopulmonary bypass.

PMID- 8865702
TI  - [Hemodynamic changes during laparoscopic cholecystectomy under different
      anesthesia methods].
AB  - We measured cardiovascular changes associated with insufflation of carbon dioxide
      and the reverse Trendelenburg position during laparoscopic cholecystectomy.
      Twenty eight ASA I and II patients were assigned to three groups depending on the
      anesthesia method. Inhalation anesthesia (I) group (n = 10) was maintained with
      nitrous oxide-oxygen-isoflurane (GOI), fentanyl (F) group (n = 10) was maintained
      with GOI and fentanyl (4.8 +/- 0.9 micrograms . kg-1), and epidural (E) group (n
      = 8) was maintained with GOI and continuous epidural infusion (1.5% lidocaine, 5
      ml . h-1). Swan-Gantz catheters were inserted to the patients in groups F and E.
      Heart rate and arterial blood pressure increased significantly in group I and
      this elevated pressure was difficult to control using even high concentrations in
      isoflurane. Heart rate, arterial blood pressure, right atrial pressure, pulmonary
      arterial pressure cardiac output, and systemic and pulmonary vascular resistance
      were not significantly changed in groups E and E. Stroke volume decreased
      significantly in group F after pneumoperitoneum. Our result showed that
      hemodynamics during laparoscopic cholecystectomy were the most stable in group E.

PMID- 8865703
TI  - [Enzyme saturation of sevoflurane in piglets at clinically-used concentrations].
AB  - To investigate if sevoflurane saturates the metabolic capacity of the enzymes
      responsible for sevoflurane at clinically-used concentration ranges, we compared
      plasma fluoride levels and urinary excretion of inorganic fluoride in piglets
      after (1) low concentration sevoflurane anesthesia versus (2) high concentration
      sevoflurane anesthesia. Eleven male piglets, weighing 18-23.5 kg, were randomly
      divided into two groups: 1) L group: five animals were anesthetized for two hours
      with sevoflurane at 0.8% end-tidal concentration (0.4 MAC); 2) H group: six
      animals were anesthetized for two hours with sevoflurane at 3.0% end-tidal
      concentration (1.4 MAC). Plasma inorganic fluoride levels, blood sevoflurane
      concentration, urinary inorganic fluoride concentration and urine volume were
      measured. The blood sevoflurance concentration in both groups reached their
      plateau levels 30 min after the start of anesthesia. The plateau levels in the H
      and L groups were 275-306 microM and 105-115 microM, respectively. The plasma
      fluoride concentrations reached plateau levels 60 min after the start of
      anesthesia in both groups. The H group showed significantly higher plasma
      fluoride levels than the L group during sevoflurane anesthesia. The H group also
      showed significantly higher urinary excretion of inorganic fluoride than the L
      group. Therefore, metabolite production levels in the H group were significantly
      higher than the L group. These results suggest that low concentration sevoflurane
      anesthesia did not saturate the metabolic capacity of the enzymes responsible for
      defluorination of sevoflurane in piglets.

PMID- 8865704
TI  - [Portal and peripheral blood insulin concentrations and arterial ketone body
      ratio before and after glucose infusion during gastrectomy].
AB  - The effect of glucose infusion on portal and peripheral blood immunoreactive
      insulin (IRI) concentrations and arterial ketone body ratio (AKBR) during
      gastrectomy were evaluated on twenty patients divided into two groups. Portal and
      peripheral blood IRI concentrations, AKBR, total ketone body concentration (TKB:
      acetoacetate + beta-hydroxybutyrate), and blood glucose were determined before
      and 30, 60, and 120 minutes after 25g glucose infusion in 30 minutes in ten
      patients (group 1) and 50 g glucose infusion in 30 minutes in ten patients (group
      2). In both groups, the rate of increase in the portal blood IRI concentration
      was markedly higher than that in the peripheral blood IRI concentration after
      glucose infusion and AKBR increased and TKB decreased with the increase of the
      portal blood IRI concentration. These findings suggest that the peripheral blood
      IRI concentration does not reflect the pancreatic insulin secretion after glucose
      infusion during surgery and that portal insulin plays an important role for
      elevating and maintaining AKBR at higher levels. On the other hand, in both
      groups, the blood glucose had its peak just after completion of glucose infusion
      and then decreased gradually. After glucose infusion, however, the blood glucose
      in group 2 increased markedly and was significantly higher than that in group 1.
      It is suggested that, during surgery, glucose infusion rate of 50 g in 30 minutes
      may be too rapid.

PMID- 8865705
TI  - [Postoperative urinary ulinastatin secretion and renal function in hepatectomized
      patients with and without liver cirrhosis].
AB  - We compared ulinastatin secretion into urine with renal function during
      postoperative period in three groups, hepatectomized group with liver cirrhosis
      (LC(+), n = 7), hepatectomized group without liver cirrhosis (LC(-), n = 4) and
      subtotal gastrectomized group with normal liver function (GR, n = 7). In LC(+)
      group, N-acetyl-beta-D-glucosaminidase (NAG) increased above normal upper limit
      throughout the postoperative period. Ulinastatin (UTI) also increased but the
      increase was not remarkable. In LC(-) group, NAG increase but not significantly
      compared with the preoperative value. UTI increased from 5.8 +/- 3.0 IU.mg x Cr-1
      to 30.8 +/- 16.6 IU.mg x Cr-1 and 39.9 +/- 9.0 IU. mg x Cr-1 on the 1st and 3rd
      postoperative day respectively. In GR group, there was no change in NAG value.
      UTI on the 3rd postoperative day increased significantly (from 10.0 +/- 7.7 to
      75.4 +/- 39.0 IU.mg x Cr-1). A small urinary secretion of UTI and increased NAG
      during postoperative period in LC(+) group suggest that UTI might play an
      important role in postoperative renal dysfunction in patients with liver
      cirrhosis.

PMID- 8865706
TI  - [Evaluation of postoperative hypoxemia with a pulse oximeter].
AB  - We investigated postoperative hypoxemia by monitoring of SPO2 with a pulse
      oximeter for the first 5 hours in the ward. Forty-eight adults were divided into
      the general anesthesia along (G) group and the combination of epidural and
      general anesthesia (E) group. The patients were randomly administered either 3 l.
      min(-1) oxygen with face mask for the initial 3 hours or room air. Postoperative
      Spo2 values in the patients who breathed room air in both groups were less than
      94% in 33% of G group and 50% of E group. 3 l. min(-1) oxygen inhalation through
      the face mask was enough to avoid postoperative hypoxemia in both groups; the
      mean values of Spo2 were 99% in G group and 97.9% in E group. Spo2 rapidly and
      significantly decreased after stopping the oxygen inhalation to under 94% in 25%
      of G group and 58% of E group. Significant correlations were found between Spo2
      levels and both age (R = 0.75) and preanesthetic Spo2 (R = 0.66) in G group. Spo2
      was significantly lower in the patients whose anesthesia was stopped after 5 p.m.
      than in those who were weaned before 5 p.m. In conclusion, there is a high
      incidence of postoperative hypoxemia for several hours in the ward, which can be
      relieved by 3 l. min(-1) oxygen inhalation with face mask.

PMID- 8865707
TI  - [Continuous monitoring of blood volume change by measuring hematocrit during
      cardiopulmonary bypass].
AB  - The usefulness of the continuous monitoring system of blood volume change (BV%),
      by using measured hematocrit, has been evaluated during cardiopulmonary bypass
      (CPB). Twelve patients for CABG were studied. The optical sensor was incorporated
      in the venous outlet site of CPB to measure Hct and hemoglobin oxygen saturation.
      The infusion of the cardioplegia caused a sharp deviation in BV%, and the use of
      extracorporeal ultrafiltration helped to reduce BV% rapidly. At the end of CPB,
      BV% was -1.4 +/- 7.7% and showed a good correlation with total water balance
      during CPB (r = 0.75, P < 0.01). However, the discrepancy between BV% and the
      positive water balance was observed in a case with LOS. This suggests fluid
      maldistribution from intra- to extra-vascular space. Continuous BV% monitoring
      during CPB is useful as an index of water balance and for assessing an optimum
      blood volume.

PMID- 8865708
TI  - [Effects of prostacyclin (PGI2) on pial vessel diameter and carbon-dioxide
      reactivity in cats].
AB  - We studied the effects of prostacyclin (PGI2) on the pial vessel diameter (D) and
      CO2 reactivity in cats. Nineteen cats, weighing 1.6-4.0 kg, were divided into two
      groups; PGI2 administration group (n = 10) and the control group (n = 9). The
      animals were anesthetized with midazolam, fentanyl, pancuronium and nitrous
      oxide/oxygen and ventilated mechanically. The pial vessels diameter (D) was
      classified into 4 groups (D < 50 microns, 50 < or = D < 100 microns, 100 < or = D
      < 200 microns, D > 200 microns). The vascular dynamics was examined through the
      closed cranial window with intravital epifluorescence microscopy on which a video
      camera was mounted. The measurements were carried out under the steady state of
      hypo-, normo-, and hypercarbia, respectively and the CO2 reactivity (delta
      %D/delta CO) was calculated. Under the induced hypotension with PGI2 (30%
      reduction in mean arterial pressure), pial vessels were significantly dilated,
      but there was no change in CO2 reactivity in terms of vessels diameter. The
      vessels with diameters of less than 50 microns were more dilated compared with
      those with larger diameters. We concluded that pial arterioles were dilated with
      PGI2 but it had no effects on CO2 reactivity.

PMID- 8865709
TI  - [The volume and pH of gastric fluid in elective surgical patients after
      preoperative oral fluid intake].
AB  - The effect of preoperative oral fluid intake on the volume and pH of gastric
      fluid was examined in 45 elective surgical patients ranged in ages from 18 to 70
      years. Two hours preoperatively they all received oral roxatidine 75 mg with 10
      ml water, immediately followed by 150 ml oral water or 150 ml refreshing drink or
      no fluid as control. Just after the induction of anesthesia, a Salem-sump tube
      was put down to the stomach to collect gastric fluid in each patient. The volume
      and pH of gastric fluid taken were 10.9 +/- 7.9 ml, 16.3 +/- 2.3 in control
      group, 8.0 +/- 6.0 ml, 6.2 +/- 2.4 in the water group and 6.3 +/- 6.0 ml, 7.1 +/-
      1.7 in the refreshing drink group. As there were no significant differences in
      gastric pH values in the three groups, the highest value was found in the
      refreshing drink group. No significant difference in VAS of hungry and thirsty
      feeling was found among the three groups. We conclude that preoperative oral
      water or refreshing drink with roxatidine 75 mg 2 hours before the start of
      anesthesia may not increase the risk of aspiration during the induction of
      anesthesia.

PMID- 8865710
TI  - [The effect of hypertonic saline infusion on lumbar epidural anesthesia].
AB  - The author compared hemodynamic effects of fluid loading during epidural
      anesthesia with 7.2% hypertonic saline (HS), lactate Ringer's (LR) or isotonic
      saline solutions in 24 ASA 1 patients undergoing elective lower abdominal or
      pelvic surgery, allocated randomly into three groups. The first two groups,
      patients received equal amounts of sodium (2.2 mmol.kg-1), and the latter group,
      isotonic saline solutions for 1-2 ml.kg-1.h-1 as control. After epidural
      injection (2%mepivacaine 0.1 ml.cm(Height)-1), fluid loading was performed for 20
      minutes. The volume of fluid loading was significantly larger in group LR (979.3
      +/- 154.7 ml) than the other two groups (HS: 104.5 +/- 20.0 ml, NS: 48.8 +/- 8.3
      ml) (P < 0.05). The number of blocked segments was similar in three groups.
      Magnitude of hypotension was no significantly different among the groups 20
      minutes after fluid loading, but recovered to the control level in group HS. In
      all groups heart rate decreased but the decrease was significant only in group
      HS. But, in group HS, stroke index increased after fluid loading and remained
      elevated. Increase of extracellular volume in group HS was observed by
      bioelectrical impedance analysis as in group LR. The author concludes that HS may
      be useful especially in the case not requiring a large volume of fluid loading.
      Finding ideal concentration, volume, and speed of infusion of intravenous fluids
      would be clinically useful.

PMID- 8865711
TI  - [Does the difference in anesthetic methods influence postoperative nitrogen
      balance?].
AB  - To evaluate the influence of anesthesia on postoperative nitrogen balance after
      upper abdominal surgery, twenty-seven patients undergoing the surgery were
      investigated. They were allocated randomly to three groups receiving different
      anesthetic methods, i.e., epidural anesthesia, general anesthesia or balanced
      anesthesia. In the epidural anesthesia group, anesthesia was maintained with 0.5%
      isoflurane, nitrous oxide and oxygen supplemented with epidural analgesia
      extending from Th 1 to L 3. In general anesthesia group, anesthesia was
      maintained with isoflurane, nitrous oxide and oxygen. In balanced anesthesia
      group, anesthesia was maintained with 0.5% isoflurane, nitrous oxide, oxygen and
      intravenous fentanyl. Epidural fentanyl was used for postoperative analgesia in
      all groups. There was no significant difference in the cumulative nitrogen
      balance for three days among the three groups. Postoperative values of IL-6 and
      CRP also did not differ significantly among the three groups. Postoperative WBC
      was significantly higher in the balanced anesthesia group than in other two
      groups. The results suggest that the difference in anesthetic methods does not
      influence postoperative nitrogen balance.

PMID- 8865713
TI  - [Anesthetic management of a patient with tuberous sclerosis].
AB  - Tuberous sclerosis is characterized by facial angiofibromatosis, epilepsy, and
      mental retardation. There have been only a few reports of anesthetic management
      of patients with tuberous sclerosis. We managed a 22-year-old patient with
      tuberous sclerosis using nitrous oxide (67%) in oxygen supplemented with fentanyl
      and midazolam. There were no untoward events related to anesthesia and surgery.
      Problems in managing patients with tuberous sclerosis are also discussed.

PMID- 8865712
TI  - [Effective treatment of a man with head injury and multiple rib fractures with
      epidural analgesia].
AB  - A 46-year-old man involved in a traffic accident was admitted to our university
      hospital for treatment of acute subdural hematoma of the brain, multiple rib
      fractures and hemothorax. On admission, he manifested disturbance of
      consciousness, and his left upper and lower extremities were paralyzed. Blood gas
      analysis revealed hypoxia, and he was nasotracheally intubated. He was
      mechanically ventilated with 10 cmH2O positive end-expiratory pressure for
      treatment of rib fractures following surgical removal of the subdural hematoma
      and insertion of a sensor into the epidural space for measurement of intracranial
      pressure. Despite continuous intravenous infusion of midazolam and buprenorphine,
      he was agitated and thrashed from side to side, probably due to severe chest pain
      caused by rib fractures. Agitation was effectively controlled by continuous
      thoracic epidural administration of morphine and bupivacaine. Intracranial
      pressure did not increase, and epidural analgesia was without sequelae. The
      patient's level of consciousness gradually improved, rib fractures were treated
      and he was extubated on the 25th hospital day. These findings indicate that
      epidural analgesia is useful for controlling pain-related agitation caused by
      head and chest injuries if increased intracranial pressure is not present.

PMID- 8865714
TI  - [Cesarean section in a patient with uncontrolled hyperthyroidism, preeclampsia,
      and congestive heart failure].
AB  - A case of a pregnant woman who underwent urgent cesarean section is presented.
      The patient had severe hyperthyroidism, preeclampsia, and congestive heart
      failure, which had not been treated until 36 weeks of gestational age. At 38
      weeks, fetal distress occurred and an urgent cesarean section was performed
      successfully under epidural anesthesia with preoperative treatments using iodide,
      hydrocortisone and propylthiouracil. The patient required postoperative intensive
      care for heart failure. Thyroid function of the neonate was almost normal. No
      abnormality was observed except low birth weight.

PMID- 8865715
TI  - [Intraoperative use of plasma-derived activated factor VII (F VII a) in a
      hemophilia A patient with inhibitors].
AB  - We treated a 1-year 9-month-old boy with severe hemophilia A who developed high
      level of F VIII inhibitor. A placement of an implantable intravenous access
      device was scheduled under general anesthesia. After a slow induction using
      oxygen, nitrous oxide and sevoflurane, a peripheral venous line was placed and
      plasma-derived F VII a was infused. A catheter was inserted via the jugular vein
      to the SVC and it was connected to the device placed subcutaneously in his right
      chest wall. The peroperative blood loss was slight, and anesthesia and surgery
      went uneventfully.

PMID- 8865716
TI  - [Anesthetic management for AICD (automatic implantable cardioverter
      defibrillator) implant surgery].
AB  - We studied anesthetic management and monitoring during AICD (automatic
      implantable cardioverter defibrillator) implantation. For anesthetic management,
      complete sedation and amnesia are needed during implantation procedures with
      rapid awakening and extubation after the surgery. We chose inhalation anesthesia
      supplemented with small doses of fentanyl or thiamylal. Monitoring for AICD
      implantation should be less invasive, continuous and rapid in responsiveness. For
      brain and cardiac monitoring, a combination of near infrared spectroscopy and
      transesophageal echocardiography was quite useful.

PMID- 8865717
TI  - [Mouth mask method for fiberoptic tracheal intubation in difficult intubations].
AB  - We tried 72 fiberoptic tracheal intubations (FTI) using a mouth mask in difficult
      intubation cases. In this method, ventilation is performed via only the mouth
      using a mask applied over the mouth (mouth mask) and FTI can be done via a
      nostril with no hindrance from the mask in anesthetized patients. We have been
      using an infant or child type Seal Mask (Gibeck Respiration) for the mouth mask
      or a specially made mouth mask. An oral airway is usually inserted and the
      nostril of one side is plugged with cotton. FTI is performed by another
      anesthesiologist. An endotracheal (ET) tube capped with a rubber diaphragm is
      passed through another nostril, and a fiberscope is inserted through the ET tube.
      The subsequent technique is the same as that of the usual FTI for awake patients.
      Intubations were successful in all cases except 2; in one, ventilation was
      impaired even with oral airway in place, and in the other, bleeding in upper
      airway due to jaw injury from traffic accident hindered the sight of the scope.
      Mouth mask method for FTI is safe, useful and practical in difficult intubations
      with little discomfort to the patient.

PMID- 8865719
TI  - [Effect of intra-operative fluid on renal function during hypotensive anesthesia
      with trimethaphan].
AB  - During induced hypotensive anesthesia in 26 cases with trimethaphan, either
      Ringer's lactate solution (LR group) or 2/3 lactate-saline solution (2/3 LS
      group) was infused at the same rate. Urine volume, creatinine clearance (Ccr),
      FENa, urinary gamma-GTP index and urinary Na/K ratio were determined before
      hypotension, during hypotension and after the operation. During hypotension, FENa
      and urine Na/K ratio decreased in both groups. In 2/3 LS group, these remained
      low after the operation compared with the values before hypotension and in LR
      group. These results suggest that LR solution might depress an endocrine response
      which is induced by hypotensive anesthesia. As urine volume and Ccr were
      unchanged by hypotension, and infusion of colloid solution (Hespander) could not
      increase these figures, circulating blood volume might not be decreased during
      hypotensive anesthesia. Since urinary gamma-GTP index increased slightly during
      hypotension or after the operation, there might have been a slight epithelial
      cell damage of tubules with hypotensive anesthesia.

PMID- 8865718
TI  - [Acid base changes and muscle relaxants].
AB  - Previous publications have provided conflicting results concerning the effects of
      respiratory and metabolic acid base changes on the neuromuscular effects of
      nondepolarizing muscle relaxants. The varying results can be attributed not only
      to experimental design or species difference, but also to the accompanying
      changes in the pharmacokinetics in vivo. Using the phrenic nerve-hemidiaphragm
      preparation of rats, in which many variables of in vivo studies can be
      eliminated, respiratory and metabolic acid-base changes were induced by varying
      carbon dioxide (PCO2) and bicarbonate (HCO3) concentrations in the Krebs'
      solution and their effects on the potencies of muscle relaxants were compared.
      Decreasing pH by increasing Pco2 or by decreasing HCO3 increased the potencies of
      the monoquaternary relaxants (d-tubocurarine, vecuronium and rocuronium), while
      pH changes did not affect the potencies of the bisquaternary relaxants
      (metocurine, pancuronium and pipecuronium). Above difference between mono- and
      bisquaternary relaxants may reflect pH-induced changes in the ionization of the
      tertiary ammonium and resulting in changes in the sensitivity to the anionic
      nicotinic receptors. Neostigmine-induced antagonism was not affected by acid-base
      changes. These results in vitro were compared and correlated with the previous
      results in vivo.

PMID- 8865720
TI  - [Changes in gastric intramucosal pH and hepato-splanchnic oxygen extraction ratio
      after heart surgery].
AB  - The Do2/VO2 balance of splanchnic organs after heart surgery was evaluated using
      two different methods; the measurement of hepato-splanchnic oxygen extraction
      ratio (OERspl) and gastric intramucosal pH (pHi) employing a hepatic venous
      catheter and a gastric tonometric catheter. Systemic oxygen extraction ratio was
      within normal ranges during the 24 hours of the experiment, but pHi decreased and
      OERspl increased significantly at 6 hours after admission to the ICU. Both pHi
      and OERspl returned gradually to normal levels after 24 hours. We conclude that a
      period of 24 hours is required to restore sufficient blood flow in the visceral
      organs to meet oxygen demand and that the pHi reflects the splanchnic DO2/VO2
      balance as well as OERspl.

PMID- 8865721
TI  - [Imbalance of blood flow induced by sympathetic block was corrected by
      prostaglandin E1].
AB  - The purpose of this study was to investigate the effect of prostaglandin E2
      (PGE1) on imbalance of blood flow induced by sympathetic block. Seven mongrel
      dogs were anesthetized with intravenous pentazocine 0.5 mg. kg-1, diazepam 0.1
      mg. kg-1 and pancuronium 0.1 mg. kg-1. Bilateral brachial arterial blood flows
      were measured using an ultrasonic transit time flowmeter (Transonic T201,
      Advance). After a thoracotomy, left stellate ganglion block (SGB) with 0.5%
      mepivacaine was performed for sympathetic block. Left brachial arterial blood
      flow increased significantly by 80% 15 min after SGB, and statistically
      significant decrease (13%) in right brachial arterial blood flow occurred 15 min
      after left SGB. After intravenous infusion of PGE1 at a rate of 150 ng. kg-1. min
      1 for 10 min, left brachial arterial blood flow increased (127%) still, and right
      brachial arterial blood flow returned to the pre-value. As to peripheral
      circulation, a combination of SGB and intravenous infusion of PGE1 was more
      effective than SGB alone. Moreover, the administration of PGE1 may improve
      imbalance of blood flow induced by sympathetic block.

PMID- 8865722
TI  - [The effect of prostaglandin E1 on body temperature, catecholamines and stress
      hormones during prolonged surgery].
AB  - The effects of prostaglandin E1 (PGE1) on body temperature, catecholamines and
      stress hormones were evaluated in 10 patients undergoing elective prolonged
      surgery over 12 hours. PGE1 (0.03 microgram.kg-1.min-1) was administered in 5
      patients and was not administered in 5 patients. Deep skin-surface temperature
      gradients were 5.1 +/- 2.3 degrees C in PGE1 non-administered group and 0.8 +/-
      0.9 degree C in PGE1 administered group (P < 0.05). Pharyngeal-skin surface
      temperature gradients were 8.8 +/- 2.1 degrees C in PGE1 non-administered group
      and 1.5 +/- 1.5 degrees C in PGE1 administered group (P < 0.05). There were no
      significant differences between the two groups in respects to catecholamines,
      stress hormones, lactate level and blood sugar. PGE1 0.03 microgram.kg-1.min-1 is
      effective in maintaining peripheral circulation without causing body temperature
      changes during prolonged surgery.

PMID- 8865723
TI  - [Effect of ulinastatin on delayed neuronal death in the gerbil hippocampus].
AB  - The effect of ulinastatin on delayed neuronal death was studied in the gerbil.
      The animals were divided into 2 groups according to the temperatures of the
      temporalis muscle, tympanic membrane, and the rectum. One group consisted of 36
      animals in whom the temperature was maintained at 36.5 degrees C and the another
      was at 38 degrees C. They were anesthetized with isoflurane and injected
      intravenously with 5 ml.kg-1 of normal saline solution, 100 mg.kg-1 of alpha
      tocopherol, 250,000 units.kg-1 of ulinastatin, or 500,000 units.kg-1 of
      ulinastatin, respectively. Transient ischemia was then induced by occluding
      bilateral common carotid arteries for 5 min. Six days later, they were
      sacrificed, and the brain tissues were fixed and stained for histopathological
      analysis of hippocampal CA1 regions. alpha-Tocopherol and ulinastatin prevented
      delayed neuronal death in the 36.5 degrees C group, but did not in the 38 degrees
      C group. alpha-tocopherol is recognized as an intrinsic radical scavenger, and
      known to prevent delayed neuronal death. Compared with 100 mg.kg-1 of alpha
      tocopherol, 500,000 units.kg-1 of ulinastatin had the same protective effect on
      delayed neuronal death at 36.5 degrees C. We concluded that administration of
      ulinastatin prevented delayed neuronal death at 36.5 degrees C.

PMID- 8865724
TI  - [The metabolism of glucose and lipids in patients with liver disease undergoing
      upper abdominal operation and the influence of the difference of intraoperative
      fluids].
AB  - To clarify the change of glucose and lipids metabolism in patients with liver
      disease undergoing upper abdominal operation, we examined the serum level of
      glucose, total ketone body, free fatty acid and l-lactate. At the end of the
      operation, 1-lactate level increased and total ketone body level elevation was
      suppressed as the bleeding increased. Also in patients undergoing hepatectomy,
      total ketone body level elevation was suppressed. From these results, we
      concluded that gluconeogenesis and utilization of fatty acid in the liver were
      augmented. These metabolic changes were not different between the group infused
      with lactated Ringer and the group infused with acetated Ringer.

PMID- 8865725
TI  - [Damage of intestinal mucosal barrier function after fluid resuscitation during
      hemorrhagic shock].
AB  - The aim of this study is to evaluate the effects of fluid resuscitation during
      hemorrhagic shock on bacterial overgrowth, bacterial translocation and intestinal
      pathology. Thirty male Sprague-Dawley rats were divided into three groups as
      follows: sham shock (anesthesia and femoral artery catheterization, control) was
      performed on group C, on group B, blood was withdrawn and maintained at a mean
      blood pressure of 25 mmHg for 30 min, followed by resuscitation with whole shed
      blood; and on group L, shock was induced by the same method, followed by
      resuscitation with the same shed blood volume of lactated Ringer's solution. Rats
      were sacrificed at 24h postshock, and bacterial cultures of blood, liver,
      mesenteric lymph node and cecum were obtained for standard bacteriological
      examinations. Furthermore, histologic examination of the end of the ileum was
      performed. The results indicate the pathologic mucosal injury, bacterial
      overgrowth and the high magnitudes of translocation occurred more frequently in
      group L than in groups C and B. Thus, resuscitation with lactated Ringer's
      solution alone for hemorrhagic shock induces intestinal histologic damage and
      bacterial overgrowth and leads to increase bacterial translocation.

PMID- 8865726
TI  - [Intrahepatic antioxidative enzymes during hemorrhagic shock].
AB  - A histochemical study on the distribution of intrahepatic Cu-Zn SOD, Mn SOD and
      catalase was made using rat models for hemorrhagic shock. Hemorrhagic shock with
      an average blood pressure of 40 mmHg was created and blood was circulated again
      two hours later. Before the shock, Cu-Zn SOD was homogeneously distributed in
      hepatic lobuli; and, in cells, it was predominantly distributed in cytoplasms.
      With the progress of the shock, the number of Cu-Zn SOD began to decrease in the
      region around the central veins of liver; and, in cells, it came to be
      distributed predominantly in cell nuclei. Even after the circulation of blood,
      similar changes were observed. The changes of the distribution of Mn SOD were
      similar to those of Cu-Zn SOD. As to catalase before the shock, it was
      homogeneously distributed in lobuli; and, in cells, it was distributed in
      cytoplasms in the form of a minute granule. Unlike the cases of SODs, no
      significant change of the distribution of catalase was observed even after the
      progress of the shock. These results suggest that the functional decline in the
      protective system against active oxygen also relates to the cause of the progress
      of the cell injury even after the circulation of blood.

PMID- 8865727
TI  - [A fluoroscopic analysis of the catheters abnormally placed in the epidural
      space].
AB  - In order to know how the catheters are placed abnormally in the epidural space,
      we inserted the epidural catheters under fluoroscopy. The catheter was placed
      straightly upward when the epidural puncture was done in the center of epidural
      space. When the puncture site was nearly close to the side wall of epidural
      space, we could not insert catheter at all. When the tip of the needle was near
      the side wall and the inserting catheter slipped upward, catheter was placed
      straight. When the catheter wedged at the side wall, it made loop and curled or
      kinked. We thought that the cause of abnormal location of the catheters in
      epidural space is the right angle between the wall of the epidural space and the
      direction of catheter.

PMID- 8865728
TI  - [The influence of intrathecal NMDA receptor antagonist on the isoflurane MAC and
      on the motor function].
AB  - The effect of intrathecal administration of NMDA (N-methyl-D-aspartate) receptor
      antagonists on the isoflurane MAC (minimum alveolar anesthetic concentration),
      and on the locomotor function, were studied in Wistar rats with catheters placed
      intrathecally. We determined the isoflurane MAC after the administration of
      either a competitive NMDA receptor antagonist, AP7 (0.044-132 nmole), or a non
      competitive NMDA receptor antagonist, MK801 (0.3-90 nmole), as well as NMDA
      (0.068-204 nmole), and saline. AP7 (0.44-132 nmole) and MK801 (30-90 nmole)
      decreased the MAC. Intrathecal administration of NMDA reversed these decreases of
      MAC, but reversal effect is incomplete with AP7 132 nmole and MK801 90 nmole. In
      a locomotor dysfunction test, rats showed motor dysfunction with AP7 132 nmole (P
      < 0.05) and MK801 90 nmole (P < 0.05), but low doses did not exert these effects.
      Large doses of NMDA antagonist decreased the isoflurane MAC due to motor
      dysfunction, but low doses reduced the MAC without impairing motor function. We
      suspect that NMDA receptor antagonists play important roles in determining the
      isoflurane MAC in the spinal cord.

PMID- 8865729
TI  - [Usefulness of brachial artery pressure with forearm compression as arterial
      pressure monitoring after cardiopulmonary bypass].
AB  - The pressures in the radial and brachial artery in the same extremity were
      measured before and after cardiopulmonary bypass (CBP) in 18 patients. Brachial
      pressures were measured in two different ways, with and without forearm
      compression. The forearm compression was achieved by a swelled blood pressure
      cuff. There were no significant differences in these pressures before CBP. But
      the brachial pressures with the forearm compression were the highest among three
      kinds of pressures after CBP and there were significant differences between them.
      The aortic pressures during weaning from CBP were measured and compared with
      these pressures in 4 patients. The brachial pressures with the forearm
      compression were closest to aortic pressures. Therefore brachial pressure with
      forearm compression was recommended as a good pressure monitor when CPB was about
      to be finished. The patients were them divided into two groups. The patient is in
      the first group had less than 10 mmHg pressure difference between brachial
      pressure and radial pressure just after CPB. The patients in the second group had
      higher pressure in brachial than those in radial for over 10 mmHg just after CPB.
      There were no significant differences in duration in CPB, lowest rectal
      temperature, hematocrit and doses of catecholamines between the two groups.

PMID- 8865730
TI  - [Management of severe pain after extended maxillectomy in a patient with
      carcinoma of the maxillary sinus].
AB  - We treated a 65 year-old man with severe facial pain after extended maxillectomy
      due to carcinoma of maxillar sinus. He had been suffering from pain at rest, on
      mastication, or at treatment of surgical wound. Various kinds of analgesics had
      been tried, but his pain did not disappear. At 17 weeks after the operation, he
      came to our pain clinic. Because his pain was thought to be due to reflex
      sympathetic dystrophy (RSD), stellate ganglion blocks (SGB) were performed. After
      5 administrations of SGB, pain was reduced markedly but the pain at treatment of
      wound persisted. We thought that persistent pain would need trigeminal nerve
      block. Then Gasserian ganglion block was performed directly through an open wound
      after the operation. After the Gasserian ganglion block, the pain was diminished
      remarkably. He could tolerate procedures for facial prosthesis. Pain control
      after the operation in this patient was very efficient to improve his quality of
      life. Serum concentrations of catecholamines, serotonin and substance P were
      measured. The levels of norepinephrine and serotonin are related to the mechanism
      of pain as seen in this patient.

PMID- 8865731
TI  - [Anesthetic problems in a 480 g infant for ventriculo-peritoneal shunt surgery].
AB  - A 480 g, 38-day-old female infant underwent ventriculo-peritoneal shunt surgery
      for hydrocephalus after intra-ventricular hemorrhage. The patient was born at a
      gestational age of 25 weeks and 5 days, weighing 600 g, as one of twins by a
      cesarean section. Although respiratory distress syndrome developed, it was
      relieved with surfactant. The esophagus was easily perforated by a gastric tube.
      At the age of 7 days, PDA was closed conservatively with indomethacin. Anesthesia
      was induced and maintained with fentanyl (induction dose 4 micrograms.kg-1, total
      dose 6 micrograms.kg-1) and vecuronium. Ventilation was controlled with oxygen
      and air (FIO2 0.21-0.25). The main problems encountered by anesthetists in the
      perioperative period were; fluid management (hyperkalemia, hyponatremia, infusion
      volume), bradycardia due to increased intracranial pressure, body temperature
      control (hypothermia), and transport to the operating room. In anesthesia for
      extremely low birth weight (extremely premature) infants, utmost care and
      proficient procedure are required because of their immaturity, fragility and
      smallness.

PMID- 8865733
TI  - [Anesthesia for cesarean section: drug transfer to fetus during anesthesia].
AB  - One case of prenatally diagnosed congenital diaphragmatic hernia was reviewed in
      terms of the anesthetic managements. Concentrations of diazepam, pancuronium and
      fentanyl were measured in maternal, fetal and umbilical serum. As expectedly, the
      transition of diazepam through the placenta was large and the concentration of
      diazepam in the fetal serum was equal to that of maternal serum, but only a small
      amount of pancuronium was transferred.

PMID- 8865732
TI  - [Myoglobinuria following anesthesia with enflurane and succinylcholine in an
      asthmatic child on theophylline].
AB  - An 8-year-old asthmatic child on theophylline was anesthetized with enflurane in
      nitrous oxide and oxygen. He developed a generalized muscle rigidity after
      intravenous succinylcholine. Although the maximum rectal temperature was 37.9
      degrees C, a marked elevation in muscle-derived enzymes and myoglobinuria were
      observed. The relations among theophylline which is a derivative of xanthines,
      inhalation anesthetics, and myoglobinuria are discussed.

PMID- 8865734
TI  - [Anesthetic management of a pediatric patient with Cornelia de Lange syndrome].
AB  - We did anesthetic management on a pediatric patient with Cornelia de Lange
      syndrome presenting a peculiar look, variable physical deformities, and some
      growth and mental retardations. An 8-year-old male patient was scheduled for
      inguinal hernioplasty under general anesthesia. This patient had been suffering
      from dehydration for apodeisis and self-destructive tendency due to psychologic
      stress. Anesthesia was induced and maintained with sevoflurane and N2O in oxygen.
      The area of skin incision was infiltrated with 0.25 % bupivacaine for the purpose
      of post-operative analgesia, and as a result, psychologically and physically
      stable condition was obtained during post-operative periods. It is necessary to
      understand not only the patient's physical conditions but also mental ones in
      order to make the anesthetic management safer and more satisfactory.

PMID- 8865735
TI  - [Anesthetic management of a patient with thymoma presenting superior vena cava
      syndrome].
AB  - We report a case of thymoma presenting superior vena cava syndrome. Anesthesia
      for biopsy or excision of an anterior mediastinal mass has been associated with
      major airway and cardiac complications. Therefore, careful anesthetic management
      is necessary. The patient was kept on Fowler's position, and anesthesia was
      induced with thiamylal. The patient was intubated with succinylcholine and
      allowed to breath spontaneously until the sternal incision. Thereafter we used
      vecuronium and controlled ventilation was maintained. Intraoperatively, arterial
      pressure, central venous pressure, and right- and left-brachiocephalic vein
      pressures were monitored. After bypasses between right atrium and right- and left
      brachiocephalic vein had been made, the venous pressures decreased remarkably.
      Various methods for preventing side effects resulted in good control during the
      perioperative period.

PMID- 8865736
TI  - [Anesthetic management of ten Jehovah's Witness patients].
AB  - We experienced the anesthetic management of 10 Jehovah's Witness patients. Some
      patients accepted either blood products, autologous blood transfusion with closed
      circuit, or Cell Saver. The patients' families expressed their wish that blood
      transfusion could be done in life threatening situations against the patient's
      wish in some cases. It would be desirable to clear up an acceptable standard and
      write out it in each medical institution to avoid conflicts with the patient and
      families. Prior agreement is required among medical staffs on refusal of blood
      transfusion.

PMID- 8865737
TI  - [Lumbar and thoracic epidural anesthesia in children's hospitals in Japan].
AB  - A retrospective study of the lumbar and thoracic epidural anesthesia
      (catheterization) in infants and children younger than 12 years was undertaken in
      children's hospitals in Japan. Seventeen institutions replied to our
      questionnaire and 10 institutions experienced these procedures in the year
      preceding September 1994. The total number of the lumbar and thoracic epidural
      anesthesia performed was 324, with average of 32.4 +/- 31.1, and maximum of 113
      and the minimum of 2. The number of thoracic epidural anesthesia performed was 56
      a much smaller figure than that of lumbar anesthesia. Infants younger than 12
      months were 23 in both groups. No major complications occurred except a case of
      infection at the insertion site. The patient had herpes zoster. On the other
      hand, several institutions cast doubt on the necessity of epidural anesthesia in
      infants and children. The long-term influence on the developing nervous system
      should be investigated.

PMID- 8865738
TI  - [Risk factors of operative death and prognosis following operations for
      esophageal cancer in the elderly].
AB  - Risk factors of operative death and prognosis in the elderly following operations
      for esophageal cancer were evaluated by multivariate analyses. Data were obtained
      from 45 operations over a 14-year period in patients of a mean age of 72.6 +/-
      6.3 years. Using a multiple logistic model analysis, it was determined that the
      significant risk factor of death within 50 postoperative days was postoperative
      pulmonary complication. No other factors were significant as risk factors with
      regard to survival. Cox's proportional hazards model analysis was used to assess
      the prognostic factors of long-term survival following operations. Independent
      predictors were the stage of cancer and age. We conclude that two points are
      essential to improve the survival rate of elderly patients with esophageal
      cancer; first, postoperative special attention in order to prevent pulmonary
      complications and secondly, performing operations at as early a stage of cancer
      as possible.

PMID- 8865739
TI  - [Development of Elderly Diabetes Impact Scales (EDIS) in elderly patients with
      diabetes mellitus].
AB  - To assess the quality of life (QOL) in elderly diabetic patients, 452 elderly
      outpatients aged over 60 years old who lived in 4 districts near our hospital
      were visited at home and of them were asked to follow 83 questionnaires
      concerning QOL by professional interviewers. Using the 37 questions about the
      impact of diabetes on elderly diabetic patients, we have developed the Elderly
      Diabetes Impact Scales (EDIS). The EDIS consisted of 6 subscales (burden of
      symptoms, burden of daily life, burden of diet therapy, burden of drug therapy,
      satisfaction, worry). Responses to questions were estimated with a 4-point
      multiple-choice assessment. The impact was rated from 1 (no impact, never
      worried, or very satisfied) to 4 (very burdened, always worried, or very
      dissatisfied) for each question and total EDIS scores were calculated by summing
      up the scores of the 37 questions. The internal consistency of the EDIS and its
      six subscales were of a satisfactory magnitude (0.66-0.88). There was also a
      significant correlation between the EDIS and PGC morale scales (r = -0.48, p <
      0.001) and between the EDIS subscales and 3 moral components suggesting a
      convergent validity of the EDIS. The EDIS may be useful in evaluating the quality
      of life in elderly patients with diabetes mellitus.

PMID- 8865740
TI  - [Factors associated with increased diabetes burden in elderly diabetic patients].
AB  - To define the factors that determine the increased burden of diabetes in elderly
      diabetic patients, we examined the relationship between the Elderly Diabetes
      Impact Scales (EDIS) and physical or social factors in 383 elderly outpatients
      aged over 60 years old who answered QOL questionnaires by professional
      interviewers. The EDIS consisted of 6 subscales (burden of symptoms, burden of
      daily life, burden of diet therapy, burden of drug therapy, satisfaction, worry)
      and total EDIS scores were calculated by summing up the 4-point scores of 37
      questions. The EDIS scores were highest in patients who received insulin therapy.
      In univariate analysis, high EDIS scores were significantly associated with high
      HbA1c, low Roken ADL score, and the presence of retinopathy or neuropathy. Among
      social factors, leisure activities, housework or jobs, social network, and
      positive social support were significantly associated with low EDIS scores, while
      negative social support was associated with high EDIS scores in elderly diabetic
      patients. Multiple linear regression analysis revealed that age (younger), sex
      (women), low ADL (or diabetic complications), insulin therapy, low positive
      social support, high negative social support, economical dissatisfaction, and the
      low adaptative feeling of diabetes were significant and independent determinants
      of a high burden in diabetic patients indicated by EDIS scores in Japanese
      elderly diabetic patients.

PMID- 8865741
TI  - [Burden of dietary therapy on elderly patients with diabetes mellitus].
AB  - As a part of a QOL study in elderly diabetes mellitus, we performed an interview
      conducted by professional interviewers on the sense of burden of dietary therapy
      in 383 elderly outpatients with diabetes mellitus aged over 60 years old. We used
      a scale on Burden of Dietary Therapy (BDT) that consisted of 7 questions (calorie
      restriction, dietary balance, regular dietary habits, restriction of favorite
      food, restriction of amounts of snacks, restrictions when eating out, burden of
      total dietary therapy). The sense of burden was rated from 1 (never burdened) to
      4 (heavily burdened) for each question and the alpha coefficiency of the BDT
      scale was 0.80. Women, relatively younger elderly patients, hyperglycemic
      patients, or tablet-treated patients had higher BDT scale scores. The lower the
      positive family support scores and the higher the negative social support scores
      the greater was the BDT score. High BDT scores were significantly associated with
      low PGC moral scales (p < 0.001). The results suggest that the burden of dietary
      therapy could lower the quality of life in elderly patients with diabetes
      mellitus.

PMID- 8865742
TI  - [Analysis of patients with excellent motor recovery after large infarction in the
      middle cerebral artery territory including the cortex].
AB  - We reported 6 cases of excellent motor recovery after a large infarction in the
      middle cerebral artery territory including the cortex. All patients were men
      (aged 67 to 80); 4 had left hemiplegia and 2 had right hemiplegia. They had
      abrupt onset of focal neurologic symptoms and signs, suggesting embolic stroke.
      The consciousness level, according to the Japan coma scale, was grade II in 4
      patients and normal in the other 2. Atrial fibrillation was present in 4 patients
      and premature atrial and ventricular contractions were seen in 1 each.
      Hypertension was present in 3 patients and diabetes mellitus in 1. The motor
      plegia gradually improved after 1 to 3 days and almost completely disappeared at
      12 days after onset. All patients were eventually able to walk alone without any
      aids. However, aphasia persisted in 2 patients with left hemispheric damage and
      left unilateral spatial neglect in 3 patients with right hemispheric damage. A
      cerebral blood flow analysis by single photon emission computed tomography, using
      [123I] isopropyliodoamphetamine or technetium 99m hexamethylpropylenamine oxime,
      demonstrated increased blood flow in the frontal lobe cortex surrounding the
      infarcted region in 5 patients. These patients showed good recovery from motor
      deficit, even though, motor symptoms did not begin to improve until 1 to 3 days
      after onset of stroke. We suggest that there is a subgroup of stroke patients,
      whose severe motor deficit starts to improve even 3 days after onset of a large
      infarction in the middle cerebral artery territory including the cerebral cortex.

PMID- 8865743
TI  - [Genetic analysis of Werner syndrome in a family].
AB  - Werner syndrome (WRN) is a rare autosomal recessive disorder, one of the
      progeroid syndromes, and is characterized by features of premature aging. The
      incidence of WRN in the Japanese population, 1 in 200,000, is higher than than
      that in the Caucasian population. The genetic defect of WRN is unknown. But
      genetic linkage to several markers on the short arm of chromosome 8 has been
      reported recently. Here, we studied one family with WRN in which an affected
      individual had a papillary thyroid carcinoma and myelodysplastic syndrome. Using
      4 microsatellites closely located to the WRN locus: D8S360, D8S1055, D8S339 and
      ANK1, we analyzed the genotypes of this patient, her three siblings and her
      parents, who were first cousins. The mutative haplotype, identified through the
      generations in pedigree, helps detect a carrier or a presymptomatic patient. The
      eldest sister inherited two normal haplotypes, but the second sister inherited
      one mutative haplotype. There was no difference in clinical signs and symptoms
      between these sisters. when the WRN gene is isolated, it will help us understand
      the mechanism of aging.

PMID- 8865744
TI  - [Isolated iliac artery aneurysms associated with disseminated intravascular
      coagulation (DIC)].
AB  - An 84-year-old man was referred to our hospital on December 3, 1993, because of
      excessive bleeding after tooth extraction. Coagulation studies revealed
      thrombocytopenia (2.2 x 10(4)/microliter), increased serum levels of FDP-E (3172
      ng/ml) and D dimer (42.6 micrograms/ml), and increased plasma levels of thrombin
      atithrombin III complex (48.0 ng/ml) and plasmin-alpha 2-plasmin inhibitor
      complex (6.8 micrograms/ml). Computed tomography showed bilateral common iliac
      artery aneurysms. A diagnosis of DIC due to bilateral common iliac artery
      aneurysms was made. Heparin (10,000 U/day) administered to treat DIC resulted in
      good control, and operative repair of the aneurysms was successful. This is the
      second reported case of isolated iliac artery aneurysms associated with DIC.

PMID- 8865745
TI  - [A case of Lemmel's syndrome caused by a large diverticular enterolith at the
      peripapillary portion of the duodenum].
AB  - A 93-year-old woman admitted because of epigastralgia. Cholelithiasis,
      obstructive jaundice, acute suppurative cholangitis and acute pancreatitis were
      diagnosed on blood chemistry and ultrasonography on admission. We performed
      emergency PTCD. A calculus 4 cm in diameter was detected at the papilla of Vater
      and marked dilatation of the common bile duct and pancreatic duct. ESWL was
      performed because of her age and because endoscopical operation seemed to be
      difficult. After lithotripsy, PTC and endoscopy demonstrated a diverticulum at
      the peripapillary portion of the duodenum. Based on analysis of PTC result before
      and after ESWL, we diagnosed this case as Lemmel's syndrome (obstructive
      jaundice, acute suppurative cholangitis and acute pancreatitis) caused by a large
      diverticular enterolith at the peripapillary portion of the duodenum. ESWL
      treatment of aged patient with an enterolith is safe.

PMID- 8865746
TI  - [A basic study on gastric emptying test using barium grains and effect of drugs
      on gastric emptying in rats].
AB  - We reported an experimental study on a new non-invasive method for evaluation of
      gastric emptying by abdominal X-ray after administration of radiopaque barium
      grains. Adult male Wistar rats weighing around 200 g were used. After they were
      fasted for 24 hours, 1 ml of gruel mixed with 10 barium grains (1 mm diameter)
      was introduced into the rat stomach with a catheter. The rats were sacrificed at
      30, 60, 90, 120 and 150 minutes after the introduction of the gruel. X-rays were
      taken at each time point and grains in the stomach were counted in the X-ray
      photographs. All barium grains were emptied from the stomach in 150 minutes.
      After incision of the abdomen, the residual gastric contents were weighed. A
      positive correlation was found between the grains in the stomach and the weight
      of the contents. We studied the effects of cisapride, scopolamine buthylbromide
      and enprostil on the gastric emptying time by this method. Cisapride accelerated
      gastric emptying, whereas scopolamine buthylbromide delayed it. A prostaglandin
      E2 analog, enprostil delayed the gastric emptying. This method was found to be a
      simple procedure which is outstanding for quantitative determination and useful
      in evaluating gastric emptying functions.

PMID- 8865747
TI  - [Clinicopathologic evaluation on colorectal laterally spreading tumor (LST)].
AB  - Clinicopathologic characteristics of 92 colorectal laterally spreading tumors
      (LST) endoscopically or surgically resected were examined. Lesions were
      macroscopically classified into two categories according to their surface
      structure :(1) granular type (G type, 47 lesions), (2) flat type (F type, 45
      lesions). The size (maximum diameter) of G type lesions was 24.7 +/- 11.3 mm
      (Mean +/- SD) and that of F type lesions was 14.2 +/- 7.4 mm. The size of G type
      lesions was significantly larger than that of F type lesions (p < 0.01). Among G
      type lesions, cancerous lesion was present in 2 (25.0%) of 8 lesions 10-14 mm in
      diameter, 2 (22.2%) of 9 lesions 15-19 mm in diameter and 19 (63.3%) of 30
      lesions more than 20mm in diameter. Regarding F type lesions, cancerous lesion
      was present in 15 (46.9%) of 32 lesions 10-14 mm in diameter, 4 (80.0%) of 5
      lesions 15-19 mm in diameter and 8 (100%) of 8 lesions more than 20mm in
      diameter. The incidence of carcinoma in F type lesions was higher than that in G
      type lesions irrespective of size. F type lesions with carcinoma showed a trend
      toward a higher frequency of submucosal invasion and F type lesions with adenoma
      revealed tendency of showing severe atypia in comparison with G type lesions. The
      adenomatous component of LST showed a tubulo-villous architecture in 13 (28.3%)
      of 46 G type lesions, however none of F type lesions had a tubulo-villous
      component. These results indicated that clinicopathologic characteristics of F
      type are obviously different from G type. Furthermore, F type had a higher
      malignant potential than G type and is thought to have a more important role as a
      precursor of colorectal carcinoma than G type.

PMID- 8865748
TI  - [Glucose intolerance after percutaneous ethanol injection therapy (PEI) in liver
      cirrhosis patients with hepatocellular carcinoma].
AB  - We studied the effect of percutaneous ethanol injection therapy (PEI) on glucose
      tolerance in liver cirrhosis patients with hepatocellular carcinoma. All of 10
      patients underwent PEI and aspiration biopsy of the tumor on separate day. Two
      time oral glucose tolerance tests (OGTT), before and after PEI, were performed in
      all patients. There were no significant changes in blood glucose and insulin
      chronologically measured on aspiration biopsy and PEI. To detect changes in
      glucose tolerance, we compared the results of OGTT before PEI with those of OGTT
      after PEI. On the basis of results of OGTT before PEI, patients were classified
      to impaired glucose tolerance group (4) and diabetes mellitus group (6). Blood
      glucose at 180 minutes on OGTT after PEI showed significantly higher value than
      that of OGTT before PEI, but insulin response was not suppressed. From these
      experiments we speculate that exaggerated insulin resistance due to injected
      ethanol may be one of the factors influencing glucose tolerance after PEI.

PMID- 8865749
TI  - [Reversal of portal-systemic encephalopathy by shunt-preserving disconnection of
      portal and systemic circulation].
AB  - Obliteration of portal-systemic shunts surgically or by interventional
      radiological techniques is fairly effective in reversing intractable portal
      systemic encephalopathy (PSE), but is often associated with ascites accumulation
      and/or formation of esophageal varices. This study reports four patients with
      incapacitating PSE who were treated by interventional radiological techniques via
      percutaneous transhepatic route. One case had the shunt embolized directly. In
      the other three the blockage was placed on the proximal part of the splenic vein,
      whereby disconnecting the mesenteric-portal blood flow from the systemic
      circulation while preserving the shunt. The patient of shunt closure showed
      transient correction of encephalopathy, but developed massive ascites and
      esophageal varices, encephalopathy recurred, resulting in death from hepatic
      failure two months after the procedure. In the cases of shunt-preserving
      disconnection of portal and systemic circulation (SPDPS) immediate and permanent
      clearing of encephalopathy was achieved without manifestation of ascites or
      esophageal varices during the follow-up period of 10 to 31 months. The difference
      of portal pressure between before and after the procedure was 18 mmHg in the
      shunt-closed patient and 3 mmHg in SPDPS group. We conclude from this limited
      experience that SPDPS can be an effective and safe method in treating PSE in
      adequately selected patients.

PMID- 8865750
TI  - [A case of double pylorus on the lesser curvature of the gastric angle].

PMID- 8865751
TI  - [A case of appendiceal lesion prior to the manifestation of ulcerative colitis:
      so-called "ulcerative appendicitis" as an antecedent lesion].

PMID- 8865752
TI  - [A case of massive bleeding from rectal varices treated with endoscopic variceal
      ligation (EVL)].

PMID- 8865753
TI  - [A case of liver metastasis from so-called hepatoid adenocarcinoma of stomach
      with lipiodol accumulation].

PMID- 8865754
TI  - [A case of acquired intrahepatic portosystemic shunt via portal vein aneurysm].

PMID- 8865755
TI  - [A resected case of cholangiocellular carcinoma associated with HCV antibody
      positive liver cirrhosis].

PMID- 8865756
TI  - [A case of acute acalculous cholecystitis due to Salmonella].

PMID- 8865757
TI  - [A case report of incomplete pancreas divism with transient extreme increase of
      CA19-9].

PMID- 8865758
TI  - [A case of aplasia of the body and tail of the pancreas associated with malfusion
      of the pancreatobiliary ducts].

PMID- 8865759
TI  - [Effect of erythromycin on early delayed gastric emptying after pylorus
      preserving pancreatoduodenectomy--case report].

PMID- 8865760
TI  - [Anemia, abdominal pain and fatigue--lead can still be found].

PMID- 8865761
TI  - [Drug withdrawal therapy].

PMID- 8865762
TI  - Bioluminescence hybridization assays using recombinant aequorin. Application to
      the detection of prostate-specific antigen mRNA.
AB  - We developed microtiter well-based bioluminescence hybridization assays using the
      photoprotein aequorin as a reporter molecule. The target DNA was hybridized
      simultaneously with a capture probe and a detection probe. The capture probe was
      immobilized on the wells through digoxigenin/anti-digoxigenin interaction. The
      detection probe was biotinylated. The hybrids were determined by using aequorin
      covalently attached to streptavidin or complexes of biotinylated aequorin with
      streptavidin. The luminescence was then measured in the presence of excess Ca2+.
      The optimized protocols showed linearity in the range from 5 amol to 10 fmol of
      target DNA. In combination with reverse transcriptase polymerase chain reaction,
      the proposed assay was applied to the detection of the mRNA for prostate-specific
      antigen (PSA). PSA mRNA from a single cell, in the presence of one million cells
      that do not express PSA, was detected with a signal-to-background ratio of 2.5.
      Typical CVs obtained were 6%.

PMID- 8865763
TI  - Chemiluminescence enzyme immunoassay using bacterial magnetic particles.
AB  - A novel chemiluminescence enzyme immunoassay using bacterial magnetic particles
      (BMPs) has been developed for highly sensitive and rapid detection of
      immunoglobulin G. Antibody was immobilized onto BMPs using the heterobifunctional
      reagents sulfosuccinimidyl 6-[3'-(2-pyridyldithio) propionamido]hexanoate (sulfo
      LC-SPDP) and sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate
      (sulfo-SMCC). For the highly sensitive immunoassay method using these BMPs, a
      good relationship was obtained between the luminescence intensity and mouse IgG
      concentration in the range of 1-10(5) fg/mL. Furthermore, in order to reduce
      assay time and to simplify operations, a rapid chemiluminescence enzyme
      immunoassay method has been developed. The rapid method was completed in 10 min.
      A linear relationship was obtained between the luminescence and mouse IgG
      concentration in the range of 10-1000 ng/mL.

PMID- 8865764
TI  - Exact mass measurement of polar organic molecules at low resolution using
      electrospray ionization and a quadrupole mass spectrometer.
AB  - Hitherto, exact mass measurement experiments have usually been performed using
      high-resolution mass spectrometry. However, under the right circumstances,
      measurements with comparable accuracy may be made at low resolution. Here we
      demonstrate the use of a low-resolution single-quadrupole mass spectrometer to
      accurately mass measure organic samples analyzed by electrospray ionization,
      using a variety of glycol polymers for internal calibration. Results are
      presented from 11 samples which yield molecular signals in the m/z range 190-750,
      including data for positive, negative, and multiply-charged sample and reference
      ions. Replicate determinations of the masses of 12 ions gave values within 4.5
      ppm (1.1 millimass units, mmu) of their calculated values, with standard
      deviations no larger than 3 ppm (1.7 mmu). From a total of 88 individual 1 min
      measurements, 83 were within 5 ppm, and 87 within 2 mmu of the theoretical mass.
      The accuracy, precision, and sensitivity shown here are comparable to those
      achievable using high-resolution mass spectrometers, with the added benefits of
      simpler instrumentation and analytical technique afforded by the quadrupole mass
      analyzer.

PMID- 8865765
TI  - A comparison of two control-display gain measures for head-controlled computer
      input devices.
AB  - We compared two gain measures: One, defined as angle/angle (A/A) gain, is the
      ratio between the angle subtended by displacement of the cursor and the
      corresponding angle of head extension/flexion or rotation. The alternative
      measure, defined as displacement/angle (D/A) gain, is the ratio between the
      linear displacement of the cursor on the screen and the corresponding angle of
      head extension/ flexion or rotation. A discrete target acquisition task using
      circular targets was used to compare control-display gain measures. Operator
      performance was evaluated for three viewing distances and three gain settings of
      each measure. Average movement time and root mean squared (RMS) cursor deviation
      from a straight line path increased as viewing distance increased for A/A gain
      settings 0.75 and 1.0. That no significant distance effect was observed for any
      of the D/A gain settings indicated that it might be more suitable to fix D/A gain
      rather than A/A gain for head-controlled computer input devices. Minimum movement
      time occurred for D/A gain settings of 0.5 cm/degree and 0.67 cm/degree. One
      explanation for the observed insensitivity of performance to changes in viewing
      distance with a fixed D/A gain may be that both angular head movement and the
      accompanying kinesthetic feedback do not change for a specified cursor
      displacement as viewing distance is changed.

PMID- 8865766
TI  - Age-related differences in perceptual learning.
AB  - The present study investigated age-related differences in perceptual learning. We
      assessed performance and learning on a semantic category visual search task. We
      investigated whether prepractice was beneficial for general learning and for
      automatic attention response development. In terms of general learning,
      prepractice was beneficial, especially for older adults; however, prepractice did
      not benefit automatic attention response development. The implications of these
      results for training purposes are discussed.

PMID- 8865767
TI  - Training older adults to use automatic teller machines.
AB  - The present study assessed the success of several instructional programs in
      teaching the use of automatic teller machines (ATMs). Fifty-six older adults
      (aged 61 to 81) participated in the study, randomly assigned to each of four, 14
      member groups. The description group received only a general overview of an ATM;
      the text guide group received written instructions for performing various
      transactions on an ATM; the pictorial guide group received written instructions
      accompanied by pictures of corresponding ATM screens; and the online tutorial
      group completed a step-by-step tutorial on a simulated ATM. Participants
      practiced on an ATM simulator. They were tested after a 24-h interval on their
      ability to perform familiar transactions on an unfamiliar ATM simulator and to
      perform completely novel transactions. Accuracy was best for the online tutorial
      group, intermediate for the text and pictorial guide groups, and worst for the
      description group. These data demonstrate both the importance of providing older
      adults with ATM training and the fact that the type of training influences the
      level of performance. The online tutorial, which provided specific practice on
      the task components, best facilitated acquisition and transfer performance.

PMID- 8865768
TI  - Television captions for hearing-impaired people: a study of key factors that
      affect reading performance.
AB  - Closed captions are broadcast with television programs for special-needs viewers
      such as hearing-impaired people. We examined how caption presentation rate, small
      amounts of induced dioptric blur, and English learned as a second language affect
      the reading performance of good readers. Thirty-two college graduates with normal
      hearing and vision, half of whom learned English as a second language, read
      television captions that consisted of white capital letters equivalent in size to
      20/92 Snellen letters on a black background. Text was presented at rates of 55,
      120, and 216 words/min. Lenses of 0, 0.5, 1.0, or 1.5 diopters (D) were worn over
      the person's best refractive correction. The fastest text rate and small amounts
      of blur significantly disrupted reading performance. People who learned English
      as a second language were hindered more by presentation rate than by dioptric
      blur. Surprisingly, people with refractive errors (even though they were
      optically corrected) were hindered less by induced blur than were people with
      normally clear vision.

PMID- 8865769
TI  - Radiotherapy in early glottic carcinoma.
AB  - Radiotherapy is widely accepted as primary treatment in the T1 stage of glottic
      cancer, but controversy surrounds the proper approach to T2 lesions of the
      glottis. A retrospective review of 90 patients addresses treatment results for T1
      and T2 lesions of glottic carcinoma managed by primary radiotherapy with 60 to 64
      Gy from 1977 to 1989. Seventy-nine patients met the criteria for local control
      analysis with a minimum follow-up of 5 years. Radiotherapy alone controlled
      disease in 93% (43 of 46) of patients with T1 lesion and 18% (6 of 33) of those
      with T2 tumors (including 10 patients in whom radiotherapy was terminated at 40
      Gy because of persistent tumor). Ultimate control of disease for T1 and T2
      lesions, including surgical salvage, was 100% and 82%, respectively. Larynx
      preservation was achieved in 100% of T1 and in 45% of T2 lesions. Extension of
      tumor and impaired vocal cord mobility showed statistical significance for
      adverse prognosis (p < .001). This paper discusses how these results affect
      treatment of glottic carcinoma, particularly in the T2 stage.

PMID- 8865770
TI  - Semon's law revisited: an electromyographic analysis of laryngeal synkinesis.
AB  - Felix Semon's fascination with vocal fold paralysis led to his theory attributing
      medialization to isolated abductor paralysis. Later, the Wagner-Grossman
      hypothesis explained the vocal fold position on the basis of cricothyroid muscle
      activity. Other authors since that time have dispelled the notion of a role for
      the cricothyroid muscle in vocal fold position with paralysis. Utilizing
      laryngeal electromyography, several authors have found electrical activity
      suggestive of variable reinnervation and synkinesis. This current study included
      patients with persistent vocal fold immobility. Fourteen patients were studied:
      half with good voice and half with poor voice. The patients with good voice had a
      relatively normal arytenoid position and evidence of synkinesis. The group with
      poor voice had an arytenoid that tipped into the laryngeal inlet and had
      denervation or poor reinnervation. This suggests that the medialization and
      upright position of the arytenoid is due to synkinesis.

PMID- 8865771
TI  - Benign paroxysmal positional vertigo of posterior semicircular canal: results in
      160 cases treated with Semont's maneuver.
AB  - One hundred sixty patients affected by benign paroxysmal positional vertigo of
      the posterior semicircular canal were treated with Semont's maneuver. Complete
      recovery after only one session was achieved in more than 50% of cases. After a
      maximum of five sessions, almost all patients had recovered; only 8 needed
      another kind of rehabilitation. No drug therapy was required for any patient.

PMID- 8865772
TI  - Dimensions of the sinus tympani and its surgical access via a retrofacial
      approach.
AB  - The sinus tympani (ST) is a critical anatomic region of the temporal bone. It
      lies medial to the facial nerve, between the ponticulus and the subiculum, and
      therefore is not easily visualized by routine surgical approaches to the middle
      ear and mastoid. This limited access makes the ST a site that is notorious for
      residual cholesteatoma. An extensive evaluation of the anatomic dimensions of the
      ST was made from human temporal bones. Three hundred twenty-seven bones were
      examined at four standardized levels to describe the dimensions and anatomic
      relationships of the ST with other structures of the temporal bone. The region of
      the stapedial tendon was found to be the most limited anatomic substructure in
      the vicinity of the ST. This study demonstrates the feasibility of a retrofacial
      approach to the ST as an aid in eradication of otherwise hidden disease.

PMID- 8865773
TI  - Pneumatization of the tympanic bulla after blockage of the ventilation route
      through the eustachian tube in the pig.
AB  - To examine whether gas exchange occurs in the middle ear air cell system
      independent of the eustachian tube (ET), we occluded the middle ear clefts of
      piglets, whose tympanic bullae closely resemble the human mastoid air cell
      system, and investigated subsequent changes in the air cell system. We
      anticipated that pneumatization and development of the air cell system would
      continue if gas were exchanged through the mucosa lining the air cell system. If,
      on the other hand, mastoid air cells depend on the ET, mastoid development would
      be impaired or arrested. In noninflamed ears, pneumatization was maintained, and
      development of the air cell system continued after the middle ear cleft had been
      occluded with an acrylate adhesive and the bullar air cell system was thus
      excluded from any communication with the ET. These results indicate that the
      normal middle ear air cell system has the capacity to perform gas exchange
      independently of the ET, with gas exchange appearing to occur through the
      submucosal capillary network.

PMID- 8865774
TI  - Morphologic changes in contralateral superior vestibulo-ocular neurons following
      labyrinthectomy in the cat.
AB  - Ultrastructural changes were measured in 22 contralateral superior vestibulo
      ocular neurons (SVONs) from four cats painlessly sacrificed at 8 weeks and 25
      contralateral SVONs from four cats sacrificed at 1 year following unilateral
      labyrinthectomy. The SVONs at 8 weeks showed a 43% decrease in somal size, a 34%
      loss in rough endoplasmic reticulum (RER), a 48% loss of ribosomes, and a 47%
      decrease in the number of synaptic profiles (SPs) contacting the soma. At 1 year
      the SVONs had a 31% decrease in size, a 43% decrease in RER, a 50% loss of
      ribosomes, and a 71% decrease in SPs. Synaptic vesicles (SVs) in both groups of
      SVONs showed no change in size or shape compared to control SVs. These findings
      resemble the contralateral SVON changes that occur following excision of the
      vestibular ganglion.

PMID- 8865775
TI  - Study on adhesion factors in lymphocyte migration to the middle ear mucosa.
AB  - We investigated influences of adhesion factors on the migration of antigen
      specific IgA-forming cells (ASAFCs) to the middle ear mucosa by means of an in
      vitro lymphocyte binding assay. Peyer's patch (PP) lymphocytes from guinea pigs
      with mucosal immunization, which are rich in ASAFCs, more frequently bound with
      the inflamed middle ear mucosa than those of PP and spleen cells from animals
      with systemic immunization, in which antigen-specific IgG-forming cells (ASGFCs)
      were induced (p > .001). The bindings were not affected by antigenic and
      nonantigenic stimuli to the middle ear mucosa for producing otitis media. On
      human middle ear mucosa from 10 patients with acute mastoiditis and chronic
      otitis media, endothelial cells of newly grown vessels were stained strongly with
      intercellular adhesion molecule (ICAM)-1, and weakly with vascular cell adhesion
      molecule (VCAM)-1, platelet endothelial cell adhesion molecule (PECAM), and
      endothelial leukocyte adhesion molecule (ELAM)-1. Many lymphocytes bound mainly
      to these endothelial cells, and a few cells were observed bound to the basal
      portion of epithelial cells. The binding of lymphocytes was significantly, but
      not completely, inhibited by anti-ICAM-1 antibody (p < .001). These findings
      suggest that PP lymphocytes with activated mucosal immunity more frequently
      migrate to the inflamed middle ear mucosa, and that those migrations, after
      extravasation, may be regulated by the interaction between various binding
      factors and their receptors on lymphocytes, which is different from that of
      adhesion molecules and their ligands in the extravasation.

PMID- 8865776
TI  - Basement membrane in middle ear cholesteatoma. Immunohistochemical and
      ultrastructural observations.
AB  - We investigated the distribution of basement membrane zone (BMZ) components
      collagen type IV, collagen type VII, and fibronectin in human middle ear
      cholesteatoma, auditory meatal skin, and middle ear mucosa using both
      immunohistochemical and ultrastructural methods. Collagen type IV
      immunoreactivity of skin and middle ear mucosa is continuous in the BMZ, whereas
      cholesteatoma frequently showed absent immunoreactivity or focal discontinuities.
      Collagen type VII immunoreactivity is detected similarly within the BMZ of
      cholesteatoma and skin. Fibronectin immunoreactivity is observed within the
      dermoepithelial junction of skin and middle ear mucosa. In cholesteatoma,
      however, fibronectin immunoreactivity is markedly increased within the extrinsic
      BMZ and the subepithelial connective tissue. The ultrastructural arrangement of
      the BMZ of cholesteatoma is like that of skin; however, it exhibits distinct
      alterations of the lamina fibroreticularis and lamina densa. Our results outline
      cholesteatoma as a disease with disturbed cell matrix interactions analogous to
      those of wound reepithelialization.

PMID- 8865777
TI  - Acoustic rhinometry in the study of the acute nasal allergic response.
AB  - Acoustic rhinometry is a recently developed method for the objective assessment
      of nasal patency. In this study, acoustic rhinometry was used to measure changes
      in nasal cavity dimensions in the immediate response to nasal allergen challenge
      in eight pollen-sensitive subjects. Acoustic rhinometric changes were compared
      with subjective symptoms, as well as histamine in nasal secretions, cytology of
      nasal mucosal scrapings, and changes in olfactory function. A significantly
      greater decrease in nasal airway caliber occurred following allergen challenge as
      compared to buffer diluent challenge in the same individuals (70% +/- 7% versus
      22% +/- 5%). During an allergic response, a strong correlation was found between
      the minimum cross-sectional area and the volume of the nasal cavity measured by
      acoustic rhinometry (r = .9). However, no correlation was observed between nasal
      airway caliber and concomitant subjective congestion reported by the subjects. A
      modest decrease in olfactory function was seen following allergen challenge (3.1
      +/- 1.4 fewer odors identified correctly out of 20; p = .08). However, the
      alterations of olfactory function did not correlate with changes in nasal
      patency. The results presented in this study demonstrate that acoustic rhinometry
      has great potential as a reproducible method for the objective assessment of
      nasal obstruction occurring in nasal allergen challenge studies.

PMID- 8865778
TI  - Pharyngeal dermoids ("hairy polyps") as accessory auricles.
AB  - The purpose of this study is to clarify the origin and nature of so-called hairy
      polyps or dermoids of the pharynx, which are often thought to be a variant of
      pharyngeal teratoma. For this purpose, a case is reported of a dermoid polyp
      involving the middle ear of an infant, the features of multiple examples of
      pharyngeal dermoid polyps and teratomas received for consultation by the Armed
      Forces Institute of Pathology are examined, and selected pertinent reports from
      the literature are reviewed. All three means are used to support the conclusion
      that these lesions are choristomatous developmental anomalies arising from the
      first branchial cleft area and that they essentially represent heterotopic
      accessory "ears" (auricles) without the growth potential of a teratoma.

PMID- 8865779
TI  - Pleomorphic adenoma of the tongue base.

PMID- 8865780
TI  - Ewing's sarcoma and peripheral primitive neuroectodermal tumor: an interim
      report.
AB  - The primitive neuroectoderm and its progeny seemingly give rise to an ever
      increasing number of clinicopathologic entities. Ewing's sarcoma and peripheral
      primitive neuroectodermal tumor have recently been united by relatively unique
      antigens expressed by the MIC-2 gene, commonly coexpressed neural markers, and
      cytogenetic and molecular genetic abnormalities. Because of these factors, the
      current thinking is that Ewing's sarcoma and the peripheral primitive
      neuroectodermal tumor are parts of a phenotypic spectrum. We present an "interim
      report" on this group of neoplasms, emphasizing their presentation in the head
      and neck.

PMID- 8865781
TI  - Similar distribution of mast cells and substance P- and calcitonin gene-related
      peptide-immunoreactive nerve fibers in the adult human larynx.
AB  - The mechanisms causing supraglottic and subglottic edema in the human larynx are
      not fully understood. Substance P (SP)- and calcitonin gene-related peptide
      (CGRP)-containing nerve fibers and mast cells have been suggested to induce
      inflammation and edema in other parts of the body. In this study of the adult
      human larynx the distribution of mast cells was studied in relation to SP- and
      CGRP-containing nerve fibers. Substance P- and CGRP-immunoreactive nerve fibers
      and numerous mast cells were found in the epiglottis and in the subglottic region
      of the larynx. Only occasional mast cells and no nerve fibers showing SP- or CGRP
      like immunoreactivity were found in the vocal cords. In conclusion, the present
      study has shown that the distribution of nerve fibers showing SP- and CGRP-like
      immunoreactivity and mast cells has a similar regional variability. As the
      highest density of SP- and CGRP-containing nerve fibers and mast cells was
      present in the regions of the larynx where edema occurs, SP, CGRP, and/or mast
      cells might be involved in the pathogenesis of edema.

PMID- 8865782
TI  - Fibrosarcoma of the thyroid in a man exposed to fallout from the Chernobyl
      accident.
AB  - Since the Chernobyl accident in April 1986, a dramatic increase in the incidence
      of thyroid carcinoma has been described, especially in children. A case of
      sarcoma of the thyroid in a man exposed to the Chernobyl fallout is presented.
      Sarcoma of the thyroid is a rare finding. The present patient lived in a region
      that is known to be one of the most exposed to Chernobyl fallout. The case
      suggests a high probability of a relationship between the sarcoma of the thyroid
      and the exposure to radiation.

PMID- 8865783
TI  - Oh, my aching back: evaluation and surgical treatment of lumbar spine disorders.
AB  - Low back pain is a common cause of disability and reason for seeking medical
      care. Surgery rates for low back pain are escalating, and the overall costs
      exceed $1 billion. Primary care physicians are increasingly responsible for the
      initial evaluations and management of these individuals. Recognition of surgical
      indications by these physicians will decrease costs by initiating management and
      will limit morbidity by expediting appropriate referrals. The important aspects
      of the evaluation of low back pain are reviewed in this article. Surgical
      indications in low back pain including infection, tumor, degenerative conditions,
      and nonacute traumatic sequelae are discussed.

PMID- 8865784
TI  - Postoperative nausea and vomiting: review and clinical approaches.
AB  - Postoperative nausea and vomiting (PNV) is a common disorder at the forefront of
      ambulatory care issues. New antiemetic drugs and improved anesthetic techniques
      have decreased the incidence of anesthesia-induced PNV. Patient characteristics
      and surgical factors are now largely responsible for postoperative emesis.
      Clinicians need to understand these factors to deal effectively with PNV as the
      use of ambulatory surgery increases. Physicians should consider both prophylactic
      drug intervention and direct treatment.

PMID- 8865785
TI  - How do geriatric patients recover from surgery?
AB  - Age is often a marker for comorbid illnesses that may complicate attempts at
      surgical intervention. Careful selection is important in deciding to recommend
      surgery for geriatric patients, but selected elderly patients may even benefit
      from major surgery. Ancillary services, such as nutrition, nursing, and physical
      therapy, are particularly important components in the postoperative care of
      geriatric patients. Case series have shown the ability of geriatric patients to
      recover from major surgical procedures, including cardiac surgery, neurosurgery,
      and oncologic surgery. In general, advanced age is not a contraindication to
      surgery but it reinforces the need for careful preoperative evaluation and
      vigorous postoperative support of the patient.

PMID- 8865786
TI  - Preoperative medical evaluation in patients having joint replacement surgery:
      added benefits.
AB  - Elderly patients having elective total joint replacement surgery are at increased
      perioperative risk because of comorbid conditions. To show the importance of the
      preoperative medical evaluation for total joint replacement, we reviewed the
      records of 238 patients who had screening for total joint replacement surgery in
      1994. Of these 238 patients, 76 (32%) benefited from findings on the preoperative
      medical evaluation. Four percent of these patients were found to have a condition
      that warranted the postponement or cancellation of surgery, and others were found
      to have a condition that was immediately treatable. Some patients required
      referral to their primary care provider or to a specialist. This study emphasizes
      the importance and added benefits of the preoperative medical evaluation for
      elderly patients having elective total joint replacement surgery.

PMID- 8865787
TI  - Treatment of cervical dysplasia with large loop excision of the transformation
      zone: is endocervical curettage necessary?
AB  - Endocervical curettage (ECC) is done during most colposcopic examinations. To
      evaluate the need for routine ECC, we reviewed the records of all new patients
      seen in the colposcopy clinic at our institution from July 15, 1992, to April 15,
      1993. During the study period, ECC was done in 341 patients with an adequate
      colposcopy. Only one case of mild dysplasia was discovered after ECC in the 123
      patients referred for evaluation of cervical intraepithelial neoplasia (CIN) I or
      atypia seen on Pap smear. ECC specimens were positive for dysplastic cells in
      only 3 of 203 patients (1.4%) in whom biopsy revealed CIN I or atypia, and Pap
      smears for all 3 patients were suggestive of more severe lesions. Routine ECC
      during the initial colposcopic examination adds expense and may cause significant
      patient discomfort. ECC can be safely omitted in patients with CIN I on referral
      Pap smear and before large loop excision of the transformation zone for treatment
      of more severe lesions.

PMID- 8865788
TI  - The clinical significance of calculated versus measured creatinine clearance in
      patients with gynecologic malignancy.
AB  - Measurement of creatinine clearance remains in convenient because of the need for
      24-hour urine collection. Our study compared creatinine clearance calculated from
      serum creatinine (CC alpha) to measured creatinine clearance (MC alpha) using an
      unsupervised 8-hour urine collection at home. Forty-two women admitted to our
      gynecologic oncology service participated in this study. Twenty-six of these
      patients had cancer originating from the ovaries, 8 from the uterus, 7 from the
      cervix, and 1 from the fallopian tube. There were adequate data for 61
      collections. MC alpha using unsupervised 8-hour urine collection at home
      correlated well with CC alpha. This calculated value may be sufficient to be used
      as a guide in evaluating renal function in patients with gynecologic malignancy.
      However, if it becomes necessary to measure creatinine clearance, our data
      suggest that an 8-hour collection may be used.

PMID- 8865789
TI  - Psychologic profiles as predictors of success in a cardiovascular risk factors
      life-style intervention program.
AB  - The risk for cardiovascular events can be reduced by modifications in life-style.
      However, only a small percentage of subjects are able to adopt such changes. We
      determined whether psychologic profiles measured on entry into a life-style
      intervention program correlated with objective measurements of success after 1
      year of enrollment. When compared with patients who had dropped out, patients
      still enrolled in the program after 1 year differed statistically on scales 1 and
      6 of the Minnesota Multiphasic Personality Inventory, showing a lower level of
      paranoia and more concern about health issues. Among patients remaining in the
      program, psychologic profiles differed between those who met an objective measure
      of success (responders) and those who did not. In addition, profiles differed
      among responders as a function of the aspect of life-style that they successfully
      changed. These findings suggest that psychologic profiles can be used to identify
      which life-style changes an individual can easily adopt.

PMID- 8865790
TI  - A national survey of physicians' behaviors regarding sexual contact with
      patients.
AB  - To determine the prevalence of sexual contact between physicians and patients, we
      mailed a survey to a nationwide, randomized sample of 1,600 physicians, including
      internists, family medicine physicians, obstetrician-gynecologists, and
      ophthalmologists. The response rate was 52% (n = 787). Of all respondents, 4.5%
      reported having dated a patient and 3.4% reported having had sexual (genital
      genital, oral-genital, or anal-genital) contact with a patient. Physicians older
      than 50 years and unmarried physicians were significantly more likely to have
      dated patients. No differences in dating or sexual contact according to specialty
      or gender were found. Physicians who reported having had sexual contact with a
      patient were less likely to report negative consequences of the contact than
      physicians who had personal knowledge of sexual contact by other physicians.
      These results have implications for educational interventions for physicians.

PMID- 8865791
TI  - Physical and sexual abuse in a middle-class obstetric population.
AB  - To evaluate the prevalence of a history of physical and sexual abuse in pregnant,
      economically stable, middle-class women with access to comprehensive health care,
      we issued self-report questionnaires to prenatal orientation classes at Wilford
      Hall Medical Center from October 19, 1992, to March 15, 1993. After identifying
      women who had been physically or sexually abused, we identified the assailant,
      the number of occurrences, and injuries resulting from the abuse. Of the 563
      women who responded, 100 (18%) reported previous physical or sexual abuse. Seven
      women (1%) stated that they were physically abused during the pregnancy. Women
      were more likely to be physically than sexually abused by a spouse or lover (46%
      versus 13%). To identify women who have a history of abuse and to address their
      needs, practitioners should incorporate taking a history of physical and sexual
      abuse during the routine new obstetric visit.

PMID- 8865792
TI  - Tardive dyskinesia as a result of long-term prochlorperazine use.
AB  - Prochlorperazine is a centrally acting dopamine receptor antagonist that is most
      commonly used for the treatment of nausea and vomiting. Like many dopamine
      antagonists, prochlorperazine has the ability to induce extrapyramidal reactions
      in susceptible patients. Rarely, however, have cases of tardive dyskinesia been
      caused by the long-term use of this agent. We report the case of a patient who
      used prochlorperazine for a prolonged period and, during hospital admission, was
      found to have a new movement disorder. Alternative antiemetics that do not pose a
      risk of movement disorders, such as ondansetron and granisetron, are readily
      available and are efficacious.

PMID- 8865793
TI  - California encephalitis in Alabama.
AB  - Arthropod-borne virus (arbovirus) infections in humans are primarily central
      nervous system infections, but other clinical manifestations include febrile
      illness and fever with hemorrhagic diathesis. In the genus Bunyavirus there are
      several viruses that cause disease in humans, especially in North America; these
      include LaCrosse, Jamestown Canyon, trivittatus, and snowshoe hare viruses. The
      disease seen mainly in children is California encephalitis (usually of the
      LaCrosse subtype); this infection is widespread in the United States but is most
      prevalent in the upper Midwest, especially in rural areas. We present the first
      reported case of California encephalitis in rural Alabama; the patient was a 7
      year-old boy who came to us with fever and seizures in the summer of 1994. This
      report stresses the importance of including California encephalitis in the
      differential diagnosis when children have fever and altered sensorium after
      exposure to mosquitoes during summer months.

PMID- 8865794
TI  - Hepatitis E virus infection in an immigrant to the United States.
AB  - A patient who had recently traveled from India to Tennessee was found to have
      acute hepatitis E. Improved recognition and serologic testing have increased the
      diagnosis of hepatitis E in the United States. For those at risk, hepatitis E
      should be considered in the differential diagnosis of acute hepatitis.

PMID- 8865795
TI  - Hyperthyroidism manifested as hypercalcemia.
AB  - A patient with hypercalcemia was found to have thyrotoxicosis and no other
      underlying cause for the elevated serum calcium level. Radioiodine therapy
      relieved hyperthyroidism and hypercalcemia. We discuss the incidence of
      hypercalcemia in patients with thyrotoxicosis and mechanisms for hypercalcemia in
      hyperthyroidism.

PMID- 8865796
TI  - Cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and
      protein S deficiency in a patient with HTLV-I.
AB  - The clinical spectrum of retroviruses is expanding rapidly. Human T-cell
      lymphotropic virus type I (HTLV-I) was the first retrovirus to be described, and
      its role had been established in adult T-cell leukemia/lymphoma and tropical
      spastic paraparesis. We report the case of a 35-year-old woman with HTLV-I and
      the unusual combination of cutaneous T-cell lymphoma, tropical spastic
      paraparesis, cerebral vasculitis, and protein S deficiency. We discuss the
      relationship of all her diseases to HTLV-I.

PMID- 8865797
TI  - Cyclophosphamide in the treatment of toxic epidermal necrolysis.
AB  - A patient with non-small cell lung carcinoma and recent radiotherapy for brain
      metastases developed toxic epidermal necrolysis (TEN) shortly after therapy with
      phenytoin was initiated for a seizure. Exfoliation progressed to involve 90% of
      her body surface despite treatment with high-dose corticosteroids for 5 days, but
      sloughing and systemic toxicity ceased within 2 days of initiating therapy with
      intravenous cyclophosphamide (300 mg/day). Reepithelialization rapidly followed.
      This experience and the reports of others suggest that intravenous
      cyclophosphamide is helpful in the treatment of TEN.

PMID- 8865798
TI  - Adult-type colloid milium of hands and face successfully treated with
      dermabrasion.
AB  - Colloid milium is an unusual cutaneous disorder characterized by multiple cystic
      papules. The adult form develops in sun-exposed parts of the body in patients who
      have actinic-damaged skin. We describe the case of a patient with the classic
      clinical and histologic features of this disorder. The patient was successfully
      treated by dermabrasion to the hands and affected facial regions and, 10 months
      later, has not shown any signs of recurrence.

PMID- 8865799
TI  - alpha 1-antitrypsin deficiency and idiopathic pulmonary fibrosis in a family.
AB  - Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease of unknown
      etiology with an estimated prevalence of 3 to 5 per 100,000. We describe a
      patient with a family history of both IPF and alpha 1-antitrypsin (AAT)
      deficiency. The patient had a 6-month history of worsening dyspnea when first
      seen, and he later died of multisystem organ failure and recalcitrant hypoxemia.
      He had IPF and AAT deficiency, with the phenotype PiSZ. His father and younger
      brother died of respiratory failure due to IPF. Other family members are
      heterozygous for AAT deficiency. A variety of inflammatory diseases have been
      associated with AAT deficiency, and an association between heterozygous AAT
      deficiency and IPF has been reported in the literature. Most current theories on
      the pathogenesis of IPF suggest an aberrant inflammatory response to some
      stimulus. This family cluster and another reported in the literature suggest that
      AAT deficiency may be a factor predisposing to inflammatory lung disease
      manifested by interstitial fibrosis.

PMID- 8865800
TI  - Heterozygous alpha 1-antitrypsin deficiency (PiSZ) in an adolescent with asthma.
AB  - Although alpha 1-antitrypsin deficiency has been associated with obstructive lung
      disease in individuals possessing a homozygous phenotype (PiZZ), this association
      has not been as clearly documented in heterozygous individuals (PiMZ, PiMS, and
      PiSZ phenotypes). Information regarding the heterozygous adolescent population is
      particularly lacking, making the evaluation and treatment of such patients
      difficult. We present the case of an adolescent with a history of asthma and
      heterozygous (PiSZ) alpha 1-antitrypsin deficiency and outline our management
      with reference to appropriate literature.

PMID- 8865801
TI  - Ascites associated with antibiotic-associated pseudomembranous colitis.
AB  - We report the case of an elderly patient who had ascites due to pseudomembranous
      colitis and associated hypoalbuminemia. Computed tomography showed diffuse
      colonic wall thickening. An indium-111 scan to localize the site of infection
      showed abnormal localization of 111In throughout the colon. Despite treatment,
      the patient died. Autopsy disclosed no other cause for the ascites, except for
      possible sepsis. To study the cause of ascites in patients with pseudomembranous
      colitis, we reviewed our institutions' experience with ascites in association
      with Clostridium difficile colitis, identifying 16 cases over a 1-year period
      (which included our case). In most of the other cases, the ascites could be
      attributed primarily to another mechanism, including portal hypertension,
      congestive heart failure, and sepsis (intra-abdominal and systemic). We also
      reviewed the literature regarding the association of ascites with C difficile
      colitis.

PMID- 8865802
TI  - Primary lipomatous tumors of the cardiac valves.
AB  - A tricuspid valve mass was identified on echocardiogram in a 69-year-old man with
      ischemic heart disease, chronic obstructive pulmonary disease, pulmonary
      embolism, and pneumonia; he died with progressive respiratory insufficiency. The
      abnormal mass was ascribed initially to infective endocarditis, and the diagnosis
      at autopsy was fibrolipoma, a benign tumor. Although rare, valve tumors should be
      included in the differential diagnosis of abnormal valve masses identified on
      echocardiogram.

PMID- 8865803
TI  - Lemierre syndrome.
AB  - We report a case of Lemierre syndrome. Although it is seen infrequently, it must
      be considered in patients with sore throat or dental pain, lateral neck pain,
      sepsis, and pulmonary symptoms. Diagnosis is based on clinical presentation,
      occurrence of anaerobic septicemia, radiologic evidence of internal jugular
      venous thrombosis, and pulmonary septic emboli.

PMID- 8865804
TI  - Resolution of focal fatty infiltration of the liver.
AB  - Focal fatty infiltration of the liver has been recognized as a distinct entity
      only since 1980. It may simulate neoplastic or other low-density parenchymal
      lesions, including abscesses and hemangiomas. I report a case of histologically
      confirmed focal fatty infiltration of the liver in a man with obesity and
      alcoholism; the lesion disappeared after the patient began a program of exercise,
      weight loss, and abstinence from alcohol. The possible pathogenesis of focal
      fatty infiltration of the liver is reviewed, diagnostic techniques are described,
      and reversibility of the lesion is discussed.

PMID- 8865805
TI  - Darwinian (evolutionary) medicine.

PMID- 8865806
TI  - Both the H13 gene product and 4F2 antigen are involved in the induction of system
      y+ cationic amino-acid transport following activation of human peripheral blood
      mononuclear cells (PBM).
AB  - Prior transfection with antisense oligonucleotides to the H13 and 4F2 hc genes,
      singly or in combination, was found to inhibit phytohaemagglutinin-induced
      activation of cationic amino-acid transport system y+ in human peripheral blood
      mononuclear cells (mostly circulating lymphocytes). These effects on system y+
      function or expression mean that 4F2 hc cannot only be the molecular basis of
      system y+L (Fei, Y.-J., Prasad, P.D., Leibach, F.H. and Ganapathy, V. (1995)
      Biochemistry 34, 8744-8751).

PMID- 8865807
TI  - A liver-specific isoform of the betaine/GABA transporter in the rat: cDNA
      sequence and organ distribution.
AB  - We report the cloning of a 2.2 kb cDNA encoding a Na(+)-and Cl- dependent
      betaine/GABA (gamma-aminobutyric acid) transporter from rat liver poly(A+) RNA.
      5'-RACE revealed an additional 355 bases 5' to the 2.2 kb cDNA sequence. Northern
      analysis demonstrated two (2.2 kb and 2.6 kb) mRNA isoforms in rat liver. Betaine
      transporter mRNA was also detected in the brain, spleen, lung, and kidney using
      the 2.2 kb cDNA clone as a probe. Only the 2.6 kb mRNA from the liver hybridized
      with the 5'-RACE product.

PMID- 8865809
TI  - Stability and pH sensitivity of sulfatide-containing phosphatidylethanolamine
      small unilamellar vesicles.
AB  - The bilayer stabilization effect of sulfatide and the pH sensitivity of sulfatide
      containing 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) small unilamellar
      vesicles were examined by light scattering and the release of entrapped calcein.
      At 30 mol% sulfatide, stable DOPE/sulfatide vesicles were formed at the
      physiological pH and their stability was preserved in the presence of human
      plasma. These vesicles were found to be pH-sensitive and became leaky at pH 6.0
      or when there was a pH-gradient across the membrane bilayer. Under such
      conditions, the amount of calcein released after 24 h incubation at 37 degrees C
      was increased by one-fold compared to that found at pH 7.4. Our results suggest
      that the hydration and partial dehydration of the headgroup of sulfatide upon
      changing pH play an essential role in determining the pH sensitivity of
      DOPE/sulfatide vesicles, while the importance of the condensing effect of the
      glycolipid on membrane bilayer is less significant.

PMID- 8865808
TI  - Cloning and sequencing of the bovine cDNA encoding the mitochondrial
      tricarboxylate carrier protein.
AB  - The tricarboxylate or citrate transporter protein (CTP) catalyzes the transport
      of citrate across the inner mitochondrial membrane by an exchange for malate or
      some other anionic metabolite. Using primers based on the rat liver cDNA
      sequence, overlapping cDNA clones encoding the bovine CTP were isolated from
      bovine liver poly(A+) cDNA. The entire bovine cDNA is 1151 bp in length with 5'
      and 3' untranslated regions of 7 and 204 bp, respectively. The open reading frame
      encodes the mature protein consisting of 298 amino acids, preceded by a
      presequence of 13 amino acids. The amino acid sequence of the mature bovine CTP
      is 95.6, 94.9, 32.2% identical to that of the citrate carrier from man, rat and
      yeast, respectively.

PMID- 8865810
TI  - Carvedilol-liposome interaction: evidence for strong association with the
      hydrophobic region of the lipid bilayers.
AB  - Carvedilol (Kredex, Coreg) is a multiple action antihypertensive drug that has
      been shown to protect cell membranes from lipid peroxidative damages. In this
      study the physical and structural effects of carvedilol on lipid bilayers are
      investigated by fluorescence techniques, differential scanning calorimetry and
      other physical methods. Carvedilol binds to liposomal membranes (9:1 DMPC:DMPG)
      strongly with an apparent binding constant on the order of 10(4) M-1 in PBS (pH
      7.4). The characteristic changes in its intrinsic fluorescence properties when
      bound to liposomes suggest that this compound is situated in a non-polar
      environment. The Stern-Volmer and bimolecular quenching constants, determined
      using nitrate as the fluorescence quencher, for the free and bound carvedilol
      indicate that the carbazole moiety is at a depth of > 11 A in the lipid bilayer.
      Fluorescence anisotropy measurements show that, unlike the membrane probes DPH
      and TMA-DPH, carvedilol is relatively mobile, and does not have a rigidly-defined
      molecular orientation in the bilayers. Differential scanning calorimetry results
      indicate that carvedilol is an effective membrane "fluidizer' as it dose
      dependently lowers the gel to liquid crystalline transition temperature and
      broadens the endothermic transition. Comparative studies of interactions of
      carbazole, 4-OH carbazole and carvedilol with the model liposomal membranes
      reveal a possible role of membrane-partitioning in their antioxidant efficacy.
      These findings are discussed in perspective with the membrane biophysical
      properties of different classes of therapeutic significant lipid antioxidants in
      mind.

PMID- 8865811
TI  - Europium chelate-loaded liposomes: a tool for the study of binding and integrity
      of liposomes.
AB  - Using the biotin-streptavidin interaction as a model, we investigated the
      suitability of lanthanide chelates as encapsulated liposomal labels in liposome
      based binding assays. Large unilamellar phospholipid:cholesterol liposomes
      containing europium-DTPA chelate and biotinylated phosphatidylethanolamine were
      prepared by detergent dialysis. The resulting Eu-liposomes ([symbol: see text]
      120 nm) bound specifically to streptavidin in microtiter wells as measured by
      time-resolved fluorometric assay (TRF). The intensity of fluorescence released
      from the bound liposomes was dependent on the concentration of biotin in the
      liposome membrane, the concentration of europium entrapped in the liposomes, the
      incubation time and the amount of liposomes used in the assay. The sensitivity of
      the TRF assay allowed the detection of binding of attomole quantities of
      liposomes. The streptavidin-immobilised liposomes subjected to porcine pancreatic
      phospholipase A2 (EC 3.1.1.4) and detergents displayed a dose-dependent release
      of the encapsulated europium. Lanthanide-chelate-liposomes should prove useful
      for studies addressing binding and stability of liposomes.

PMID- 8865812
TI  - Loss of lysosomal integrity caused by the decrease of proton translocation in
      methylene blue-mediated photosensitization.
AB  - Loss of lysosomal integrity is a critical event for killing tumor cells in the
      photodynamic therapy of cancers. To elucidate the mechanism of photodamage
      induced lysosomal disintegration, we investigated the role of losing lysosomal
      proton translocation in latency loss of photosensitized lysosomes. Isolated rat
      liver lysosomes were light exposed in the presence of Methylene blue. Through
      monitoring lysosomal delta pH with Acridine orange and measuring its membrane
      potential with 3,3'-dipropylthiadicarbocyanine iodide, loss of Mg-ATP dependent
      proton translocation and decrease in electrogenicity of the proton pump were
      observed after lysosomes were photosensitized. When normal lysosomes were
      incubated for 60 min in K+ contained medium, percentage free activity of
      lysosomal enzyme beta-galactosidase increased, i.e. lysosomal latency decreased.
      In the presence of Mg-ATP, the latency loss of incubated lysosomes reduced.
      Addition of n-ethylmaleimide, a potent inhibitor of lysosomal H(+)-ATPase,
      abolished the effect of Mg-ATP on lysosomal latency. It suggests a role of proton
      translocation in protecting lysosomal integrity. Under the same conditions,
      Methylene blue photosensitized lysosomes increasingly lost latency of beta
      hexosaminidase and beta-galactosidase with light exposure, presumably due to the
      photodamage induced loss of proton pumping. In contrast, the photosensitization
      did not decrease lysosomal latency in the absence of Mg-ATP, implying that
      lysosomal integrity might not be impaired via other photodamage effects under the
      conditions of this study. These results indicate that lysosomal integrity can be
      photodestructed via the loss of proton translocation.

PMID- 8865813
TI  - Purification of a cortisol binding protein from hepatic plasma membrane.
AB  - A cortisol binding protein from rat liver plasma membranes has been solubilized
      in active form by using the zwitterionic detergent CHAPS. Two types of binding
      sites have been characterised in both native and solubilized membranes. The first
      is of high affinity and low binding capacity (12 nM; 946 fmol/mg) and the other
      one is of low affinity and high capacity of binding (344 nM; 12677 fmol/mg) for
      solubilized membranes. The purified material retained a binding activity
      comparable to that displayed by the original membrane. The specific binding
      activity was enriched about 12700-fold, with an 8% yield. Analysis of the
      purified preparation on sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis showed two protein subunits with molecular mass of 52000 and
      57000 Da. The new cortisol-specific binding membrane protein could be related to
      the nongenomic effects previously described for this hormone.

PMID- 8865814
TI  - Complexes of non-cationic liposomes and histone H1 mediate efficient transfection
      of DNA without encapsulation.
AB  - Transfection competent complexes were assembled using a three component system.
      The constituents of the basic system were plasmid DNA, cationic DNA binding
      protein (NLS-H1) and anionic liposomes (dioleoyl phosphatidylethanolamine (DOPE)
      or phosphatidylserine (PS)). In contrast to cationic liposome/DNA binary
      complexes, all of the DNA in these ternary complexes was sensitive to DNase I
      degradation and ethidium bromide intercalation. Transmission electron microscopy
      revealed that these ternary complexes formed unique structures in which the DNA
      was located either on the outside of individual liposomes or bridging two or more
      liposomes. This provides evidence that plasmid DNA encapsulation is not essential
      for transfection competency.

PMID- 8865815
TI  - Glucose transport activity and ligand binding (cytochalasin B, IAPS-forskolin) of
      chimeric constructs of GLUT2 and GLUT4 expressed in COS-7-cells.
AB  - Chimeric constructs of glucose transporters GLUT2 and GLUT4 were transiently
      expressed in COS-7 cells in order to determine regions of the proteins
      responsible for their differences in activity and ligand binding. Exchange of the
      C-terminal tail (aa 479-509) of GLUT4 failed to affect glucose transport activity
      assayed at 1 mM glucose or ligand binding (cytochalasin B, IAPS-forskolin). In
      contrast, exchange of the C-terminal half of GLUT4 (aa 222-509) for that of GLUT2
      markedly reduced ligand binding (Kd of cytochalasin B binding 1.88 +/- 0.2 microM
      vs. 0.21 +/- 0.06 in the wild-type GLUT4), and moderately (25%) reduced glucose
      transport activity. These data support the conclusion that the domains
      determining differences in ligand binding between GLUT4 and GLUT2 are located in
      the C-terminal half of the glucose transporters.

PMID- 8865816
TI  - Aldosterone-induced proteins in primary cultures of rabbit renal cortical
      collecting system.
AB  - Primary cultures of immunodissected cells from rabbit kidney connecting tubule
      and cortical collecting duct were used to study aldosterone's action on
      transcellular Na+ flux. Incubation with 10(-7) M aldosterone stimulated
      transcellular Na+ transport which was detected as an increase in benzamil
      sensitive short-circuit current. The stimulatory response was consistently noted
      after 2 h of incubation and stabilized after 6 h. 2D-PAGE was used to identify
      proteins which were induced concurrently with the increase in transcellular Na+
      flux after an aldosterone incubation of 15 h. Three aldosterone-induced proteins
      (AIPs; M(r) = 100, 70-77 and 46-50 kDa) were found in the membrane and microsomal
      fractions. Two of these appeared to have more than one isoform. A single
      heterogeneous AIP (M(r) = 77 kDa) was detected in the soluble fraction.

PMID- 8865817
TI  - Kinetic characterization of zinc binding to brush border membranes from rat
      kidney cortex: interaction with cadmium.
AB  - Extravesicular and intravesicular zinc bindings were evaluated in brush border
      membrane vesicles isolated from rat kidney cortex. The process was found to be
      time-, temperature- and substrate concentration-dependent and displayed
      saturability. Zn2+ influx measurements revealed a progressive uptake and massive
      accumulation at equilibrium which was 50 times higher than the amount that could
      have been accommodated by the intravesicular space calculated from the
      equilibrium uptake of D-glucose. Initial (5 s) and equilibrium uptakes (2 h) were
      found not to be osmotically sensitive as modified by adding mannitol to the
      medium. It was concluded from these results that the uptake involved massive
      binding of the Zn2+ to the brush border membranes components. The ionophore
      A23187 enhanced the rates of uptake and efflux of Zn2+ without affecting
      equilibrium values, suggesting binding of Zn2+ to interior sites of the
      membranes. Zn2+ flux measurements led to the conclusion that two vesicular pools
      of Zn2+ bindings existed: a small external pool, accessible to cation chelator
      (EGTA) or competitive cation cadmium and large intravesicular pool. Accumulated
      65Zn was quickly removed from its internal sites only after the membrane had been
      permeabilized by the cation ionophore A23187 in association with exchangeable
      ions like zinc and cadmium. Scatchard plot analysis revealed two distinct types
      of extravesicular binding sites. High affinity extravesicular zinc binding sites
      reached saturation at 1.6 mM zinc, had a Kd of 137 microM and the number of
      binding sites were 12 nmol/mg protein. Low affinity extravesicular zinc binding
      sites could not be saturated under experimental conditions up to 3.2 mM zinc. It
      had a Kd of 526 microM and the number of binding sites 28 nmol/mg protein.
      Interestingly intravesicular binding of zinc revealed only one type of high
      affinity binding sites (Kd of 104 microM and number of maximal binding sites 400
      nmol/mg protein). Furthermore, kinetic analysis of inhibitory effect of Cd2+ on
      extravesicular zinc bindings showed an increase in Kd of both types of binding
      sites but there was no significant change in number of maximal binding sites.
      Extravesicular zinc binding was temperature-sensitive. Arrhenius plot showed the
      break point at 30 degrees C. The apparent energies of activation were 13.36
      Kcal/mol and 3.1 Kcal/mol below and above the break points respectively. The
      inhibitory effect of sulfhydryl blocking agents on extravesicular zinc binding
      suggest the involvement of -SH groups in zinc translocation. An increase in
      initial zinc uptake was observed in the presence of outwardly directed proton
      gradient. Intravesicular pool of 65Zn was displaced by unlabelled 2 mM Zn2+ or 2
      mM Cd2+ but not by calcium present in the bathing medium. It is inferred that
      intravesicular binding sites have a high affinity and are specific for zinc. It
      is concluded from the present study that in the first instance the binding of
      zinc to the exofacial zinc binding component and concomitantly its translocation
      across the membrane, and subsequently massive binding of zinc to interior sites
      of brush border membranes occurs.

PMID- 8865818
TI  - Voltage-dependent absorbance change of carotenoids in halophilic archaebacteria.
AB  - Membrane vesicles of wild-type Halobacterium sp. mex strain show a wavy
      absorbance change which has not been so far reported in halophilic
      archaebacteria. A white mutant strain lacking carotenoids did not show the wavy
      absorbance change. The wavy absorbance change in the range of 440-590 nm was
      induced by a red flash (600-640 nm), which photoexcited electrogenic ion pumps,
      mex bacteriorhodopsin and mex halorhodopsin but not carotenoids. The wavy change
      was also caused by K+ diffusion potentials without light. These results suggest
      that the wavy absorbance change in the membrane vesicles is the voltage-dependent
      absorbance change of the carotenoids.

PMID- 8865819
TI  - A combined SAXS/WAXS investigation of the phase behaviour of di-polyenoic
      membrane lipids.
AB  - Real-time measurements of the SAXS/WAXS diffraction patterns of aqueous
      dispersions (1:1 wt/wt) of the di-polyenoic lipids di-18:2 PC, di-18:3 PC, di
      18:2 PE and di-18:3 PE were made over the temperature range 10 degrees to about 
      80 degrees C. The results of these measurements were compared to similar
      measurements performed on the corresponding di-18:0 and di-18:1 derivatives. SAXS
      measurements of the temperature dependence of lamellar repeat distances show that
      the di-polyenoic lipids undergo broad second-order transitions between their gel
      and liquid-crystal lamellar phases spanning 30-40 degrees C. The di-18:1 and di
      18:0 derivatives, in contrast, undergo abrupt first-order transitions. The gel
      phases of the di-18:0 derivatives are characterised by two-component WAXS
      patterns with a sharp component close to 0.42 nm and a broader component at
      narrower spacings. On cooling, these lipids appear to undergo an initial
      transition to an L beta, phase followed by a conversion to an Lc phase. The gel
      phases of the di-18:1 derivatives also show two-component patterns but with the
      sharp component centred closer to 0.44 nm. The di-polyenoic lipids, in contrast,
      are characterised by a single broad peak centred at a spacing of about 0.42 nm,
      close to that of conventional L beta phases. The changes in lamellar repeat
      distance accompanying the transitions in the di-monoenoic and di-polyenoic
      lipids, all of which occur in the frozen state, are very similar, indicating that
      the acyl chains of the polyenoic lipids are close to their maximum extension in
      the gel state. The WAXS patterns of the polyenoic lipids suggest that the
      saturated upper parts of the acyl chains are packed on a regular hexagonal
      lattice while their polyunsaturated termini remain relatively disordered.

PMID- 8865820
TI  - Occlusion of K+ in the Na+/K+/2Cl- cotransporter of Ehrlich ascites tumor cells.
AB  - Proteins of n-octyl glucoside solubilized membrane vesicles derived from Ehrlich
      ascites tumor cells can occlude 86Rb+.K+ displaces 86Rb+ and it is assumed that
      86Rb+ can be used as a tracer to measure K+ occlusion. The following observations
      indicate that the Na+/K+/2Cl- cotransporter is responsible for this occlusion:
      (1) Na+ does not compete for the K+ binding site, but rather stimulates 86Rb+
      occlusion. (2) K+ occlusion saturates with increasing [Na+] and [K+], the
      respective K0.5 values being 50 +/- 7 microM for Na+ and 371 +/- 63 microM for
      K+. (3) Preincubation with 1 mM ouabain does not inhibit 86Rb+ occlusion, arguing
      against the Na+/K+-ATPase as being responsible for the occlusion. This notion is
      supported by the K0.5 value for K+ being higher than reported for Na+/K+-ATPase
      and by the stimulatory effect of Na+. (4) The K+ occlusion is sensitive to [Cl-],
      and the occluded ion is protected by the presence of bumetanide during cation
      exchange chromatography. Our results suggest that occlusion measurements of
      substrate ions could be a profitable way to study the ion binding mechanism(s) of
      the Na+/K+/2Cl- cotransporter.

PMID- 8865821
TI  - Sodium-dependent carnitine transport in human placental choriocarcinoma cells.
AB  - The JAR human placental choriocarcinoma cells were found to transport carnitine
      into the intracellular space by a Na(+)-dependent process. The transport showed
      no requirement for anions. The Na+-dependent process was saturable and the
      apparent Michaelis-Menten constant for carnitine was 12.3 +/- 0.5 microM. Na+
      activated the transport by increasing the affinity of the transport system for
      carnitine. The transport system specifically interacted with L-carnitine, D
      carnitine, acetyl-DL-carnitine and betaine. 6-N-Trimethyllysine and choline had
      little or no effect on carnitine transport. Of the total transport measured,
      transport into the intracellular space represented 90%. Plasma membrane vesicles
      prepared from JAR cells were found to bind carnitine in a Na(+)-dependent manner.
      The binding was saturable with an apparent dissociation constant of 0.66 +/- 0.08
      microM. The binding process was specific for L-carnitine, D-carnitine, acetyl-DL
      carnitine, and betaine. 6-N-Trimethyllysine and choline showed little or no
      affinity. It is concluded that the JAR cells express a Na(+)-dependent high
      affinity system for carnitine transport and that the Na(+)-dependent high
      affinity carnitine binding detected in purified JAR cell plasma membrane vesicles
      is possibly related to the transmembrane transport process.

PMID- 8865822
TI  - The clinical learning environment.
AB  - This paper presents a brief review of the attributes of effective learning
      environments in clinical settings. Recent studies articulate the perceived
      importance of social and organizational factors as determinants of learning.
      Differences are evident among hospitals and among departments within hospitals
      with regard to the quality of the learning environment they offer. These
      differences are reflected in the orientation towards teaching and learning, the
      level of autonomy, variety and workload, and the quality of supervision and
      social support. Differences are also evident in the type and quality of
      opportunities for practice of important skills and in the availability of
      educational resources. These factors are perceived as major determinants of the
      effectiveness of learning in clinical settings. The implications for clinical
      teachers and administrators are discussed. The authors argue that emphasis should
      be given to the creation of supportive and well-organized learning environments
      in clinical settings. This may require a great emphasis on the role of clinical
      teachers as designers of opportunities for learning and managers of learning
      resources.

PMID- 8865823
TI  - Surgical treatment of sleep apnea syndrome.
AB  - Several surgical procedures have been developed for the treatment of sleep apnea
      syndrome. These include nasal, uvulopalatopharyngeal, and head and neck surgery,
      weight reduction surgery, and tracheostomy. Despite over 15 years of experience
      with some of these operations, there is still a lack of consensus regarding the
      indications, success rate, complications, and long-term prognosis associated with
      these procedures. The current status of these surgical procedures is reviewed.

PMID- 8865824
TI  - HIV infection and AIDS in Jerusalem: a microcosm of illness in Israel.
AB  - During the decade 1985-94, 158 individuals (124 males, 34 females) with HIV/AIDS
      were seen at the AIDS clinic of Hadassah University Hospital. They comprised 10%
      of the total reported number of HIV-infected Israelis and included 6% of all
      reported HIV-infected Ethiopians and all HIV-infected West Bank Palestinians.
      Most individuals (82%) were self-referred; 12% were detected through the local
      HIV screening clinic. Risk groups for AIDS were homo/bisexuality (39%),
      heterosexual relations (30%), intravenous drug abuse (15%), contaminated blood
      transfusions (9%), born to HIV+ mothers (1%), and hemophilia (< 1%). In 5% (all
      males) no risk factor was given. Of the 158 individuals 29 were Ethiopian
      immigrants, 25 West Bank Palestinians, and the rest were local Israelis and
      tourists. Of the 34 females seen, 21 acquired HIV heterosexually, 6 were
      intravenous drug abusers, 5 were recipients of contaminated transfusions, and 2
      were infants. An initial clinical presentation with full-blown AIDS was observed
      in 30% of the individuals. The range of clinical presentations was similar to
      that seen in western countries, with Pneumocystis carinii pneumonia,
      cytomegalovirus retinitis, mycobacterial infections and Kaposi's sarcoma seen
      most frequently. One case of disseminated cutaneous leishmaniasis was observed.
      The mortality rate during the follow-up was 55%. In 35% of individuals the
      immediate cause of death was severe bacterial infections. The Palestinian
      subpopulation presented at an advanced stage of the disease with a high incidence
      of transfusion recipients, while most HIV-infected Ethiopians presented with
      asymptomatic disease transmitted heterosexually. HIV/AIDS as seen at Hadassah
      University Hospital during 1985-94 exhibited the mixed form of Euro-American AIDS
      with additional facets of recently introduced African infection.

PMID- 8865825
TI  - Improved outcome of coronary stenting by utilizing a modified treatment protocol.
AB  - Coronary stents improve patient outcome, are easy to deploy and are now being
      utilized very frequently after coronary angioplasty. New protocols have been
      suggested to overcome the main limitations of stenting, namely subacute stent
      thrombosis, local vascular complications, and the length of hospitalization. In
      this report we describe our current results with coronary stenting in 100
      patients: we modified our standard protocol and used high pressure noncompliant
      balloons to expand the stent, added ticlopidine to some of the patients to
      inhibit platelet activity, and used the transradial approach in some patients to
      reduce the risk of vascular complications. These results were compared to those
      obtained in our initial group of 50 patients in whom we used a standard
      implantation protocol. Subacute thrombosis occurred in one patient in the current
      group of patients compared to five patients in our early experience (P = 0.026).
      There was no change in local vascular complications. This preliminary report
      shows that subacute thrombosis can almost be eliminated by the new stent
      implantation protocols. Less aggressive anticoagulation and radial artery
      catheterization can decrease vascular complications.

PMID- 8865826
TI  - Routine childhood screening for hyperlipidemia in Israel.
AB  - Screening of children and adolescents for hyperlipidemia is controversial. We
      performed a cholesterol surveillance study of 806 children aged between 6 and 14
      years. The initial cholesterol screening test was done by finger stick in the non
      fasting state. Children with cholesterol values exceeding 4.55 mmol/l
      ("borderline" risk) and their parents had their lipid profiles measured following
      a 12 h fast by venipuncture. The incidence of coronary risk factors in the
      families of children with hypercholesterolemia was estimated. Of the initial
      group, 71 children had total capillary cholesterol levels > or = 4.55 mmol/l, and
      in 65 of these children serum lipid profile was reexamined after an overnight
      fast. Fifty-five children were found to have total venous cholesterol (TVC)
      levels < 4.55 mmol/l, and 27 of the 55 had a low density lipoprotein (LDL)
      cholesterol level > 3.4 mmol/l ("borderline" risk). A positive correlation was
      found between TVC and LDL-cholesterol levels. Of the hypercholesterolemic
      children 49% had a parent with hyperlipidemia and 13% had a family history of
      premature myocardial infarction (before 55 years of age). We conclude that
      screening of children based on the presence of hypercholesterolemia or its
      possible complications in other family members may fail to identify many of the
      children with hypercholesterolemia. Thus, if thorough identification of young
      children with hypercholesterolemia is desired, inclusive population screening
      would be the most effective approach.

PMID- 8865827
TI  - Effect of human recombinant erythropoietin therapy on panel reactive antibodies
      in chronic dialysis patients.
AB  - To examine whether recombinant human erythropoietin (rhEPO) therapy results in
      decreased presensitization to foreign HLA antigens, we retrospectively analyzed
      data from 64 of 200 patients treated in a university hospital dialysis center
      between 1985 and 1995 who had undergone routine panel reactive antibody (PRA%)
      screening. Though a significant decrease in the annual frequency of highly
      sensitized patients over the years was noted, 16 patients followed for 27.1 +/-
      3.7 months after initiation of rhEPO therapy until transplantation or blood
      transfusion showed no significant overall decrease in PRA%. Six highly
      presensitized patients had moderate but significant overall decrease in PRA%.
      However, in three of these patients the PRA% was unchanged and in the other three
      patients the PRA% remained over 50%. Thus rhEPO therapy reduced the incidence of
      highly presensitized patients, but previously presensitized patients remained
      presensitized. We conclude that removal of transfusional stimulation of
      lymphocytotoxic antibody production does not appear to benefit previously
      presensitized patients, possibly due to the maintenance of B-lymphocyte clonal
      expansion by unknown factors, or even by rhEPO itself.

PMID- 8865828
TI  - A prospective study evaluating the usefulness of continuous supplemental oxygen
      in various endoscopic procedures.
AB  - The influence of oxygen supplementation on the prevalence of hypoxemia during
      endoscopic procedures was studied in 289 patients in a prospective clinical
      trial. The frequency of oxygen desaturation was found to decrease significantly
      in patients receiving oxygen via nasal prongs, compared to patients not receiving
      oxygen supplementation. The effect was demonstrated especially in patients who
      underwent an additional procedure during their endoscopic examinations. Similar
      effects were found in patients undergoing gastroscopy, colonoscopy, and
      endoscopic retrograde cholangiopancreatography. In view of the risks related to
      hypoxemia and its high prevalence in endoscopic procedures (28-50%) we recommend
      that a routine oxygen supplementation policy be considered in every patient
      undergoing endoscopy, especially when additional procedures are to be performed.

PMID- 8865829
TI  - Histology of posterior scleral foramen in normal eyes: its possible role in optic
      nerve damage in chronic open angle glaucoma.
AB  - We examined the histologic features of the posterior scleral foramen in 27
      enucleated eyes (16 during autopsy and 11 with choroidal malignant melanoma). The
      histologic findings of the posterior scleral foramen were similar to those in
      previous reports. The shape of the scleral foramen was either cylindrical or
      truncated, the latter occurring when the inner margin of the sclera projected
      with a crest-like edge pressing into the optic nerve. This configuration was
      encountered more frequently in the upper and lower temporal aspects of the
      scleral foramen in 10 eyes, while the nasal rim was free of such projection in
      all the eyes. We hypothesize that the effect of prolonged high intraocular
      pressure exerted on the axonal tissue against these crest-like edges of the non
      distensible scleral foramen might be the major factor in the etiology of early
      arcuate nerve fiber bundle defects in primary open-angle glaucoma.

PMID- 8865831
TI  - Phospholipase A2 and phospholipase D are involved in macrophage NADPH oxidase
      mediated oxidation of low density lipoprotein.
AB  - Macrophage-mediated oxidation of low density lipoprotein (LDL) under oxidative
      stress induces activation of reduced nicotinamide adenine dinuleotide phosphate
      (NADPH) oxidase. Using J-774 A.1 macrophages, the present study demonstrates that
      phospholipase A2 (PLase A2) as well as phospholipase D (PLase D) are involved in
      macrophage NADPH oxidase-mediated oxidation of LDL. Furthermore, the products of
      these phospholipases, arachidonic acid and phosphatidic acid, can induce NADPH
      oxidase activation, followed by cell-mediated oxidation of LDL. This LDL
      oxidation was shown to be dependent on extracellular calcium ions. We conclude
      that PLase A2 and PLase D can induce macrophage NADPH oxidase-dependent oxidation
      of LDL and thus can contribute to the formation of atherogenic oxidized
      lipoprotein.

PMID- 8865830
TI  - Extensive necrotizing soft tissue infection of the perineum.
AB  - Synergistic necrotizing fasciitis of the penis and scrotum was first described by
      Fournier, and remains a rare, but life-threatening disease. The reported
      mortality rates in different series range between 22 and 60%. We present a study
      of 20 patients treated over a 9 year period by early aggressive excision. Four of
      the treated patients (20%) died. A high index of suspicion, combined with early
      radical surgical intervention, is the key to effective treatment. Delayed
      diagnosis and treatment were the primary factors responsible for death.

PMID- 8865832
TI  - Attitudes of primary care physicians to the management of asthma and their
      perception of its relationship to patients' work.
AB  - The results of a questionnaire on the attitude of family physicians and general
      practitioners to the management of asthma, and their perception of the
      relationship between working conditions and asthma are reported. Family
      physicians were three times more likely than general practitioners to treat
      asthmatic patients themselves, without referral to a specialist. However, there
      were no other major differences between these two groups regarding the weight
      they attributed to the occupational factor in asthma. Overall, both groups
      routinely asked patients about their job (78%) and exposure at work (75%), but at
      least in half the cases this issue was not followed-up to determine if occupation
      related counselling or problem management were necessary. Differences in the
      primary care of asthmatics were also noted between physicians in Israel and
      America. In Israel, physicians tended to explain everything to the patients at
      the initial visit, and then leave them to cope on their own unless the episodes
      remained uncontrolled, whereas their American counterparts continued their
      educational activities in subsequent visits as well. We conclude that family
      medicine residency training in Israel, despite the inclusion of courses and
      lectures on occupational health in general and on respiratory diseases in
      particular, does not sufficiently emphasize this subject. Clinicians should be
      trained to take a more in-depth and active approach to this problem in order to
      avoid misdiagnosis and improve prevention.

PMID- 8865833
TI  - Multiple spurious laboratory results in a patient with hyperlipemic pancreatitis
      treated by plasmapheresis.
AB  - Hyperlipidemia is a known cause for acute pancreatitis. Hyperlipidemia may also
      produce multiple spurious laboratory results that may complicate the diagnosis
      and management of pancreatitis. We encountered such a patient who had the
      following spurious laboratory results: normal serum amylase activity,
      hyponatremia, and high hemoglobin levels. These laboratory artifacts were
      previously described, mostly separately. In addition, our patient had artifactual
      thrombocytopenia. The patient improved dramatically following plasmapheresis,
      which enhanced reduction of serum lipids.

PMID- 8865834
TI  - Theophylline intoxication: clinical features and pharmacokinetics during
      treatment with charcoal hemoperfusion.
AB  - We describe a 50-year-old depressive patient with severe theophylline toxicity
      that occurred as a result of attempted suicide. Her theophylline levels peaked at
      148 mg/l. She was promptly treated with charcoal hemoperfusion, and responded
      well. We describe the pharmacokinetics of theophylline removal via hemoperfusion,
      and review the literature.

PMID- 8865835
TI  - Pneumococcal psoas abscess: report of a case and review of the world literature.
AB  - A 39-year-old man was admitted to the hospital with fever and right hip pain. CT
      scan of the pelvis showed a psoas muscle abscess. Pus, which was surgically
      evacuated, grew Streptococcus pneumoniae. The patient fully recovered after 30
      days of intravenous antibiotics. Review of the literature revealed only nine
      similar cases of primary pneumococcal psoas abscess. Three cases were complicated
      with pneumococcal meningitis. In four cases there was a history of trauma to the
      involved area. Pneumococcal psoas abscess is a rare entity that carries a good
      prognosis provided early surgical drainage is performed and parenteral antibiotic
      therapy is administered to the patient.

PMID- 8865836
TI  - Fatal intracerebral hemorrhage during dental treatment.
AB  - Although chronic arterial hypertension is the leading cause of intracranial
      hemorrhage, an abrupt rise in systemic arterial pressure in normotensive people
      may sometimes induce a hemorrhagic stroke. Dental treatment is rarely associated
      with such an event. We report here on two middle-aged women, apparently healthy,
      who suffered from a fatal intracerebral hemorrhage following a dental treatment.
      On admission, high levels of arterial hypertension were found. It seems that
      trigeminal manipulation during dental treatment as well as increased serum levels
      of induced epinephrine mainly by stress and pain, and the small amounts absorbed
      from the site of local anesthesia might produce abrupt elevation of blood
      pressure, subsequent increase in cerebral blood flow and severe, even fatal
      intracerebral hemorrhage. The addition of catecholamines to local anesthetics
      should be considered. We recommend the use of benzodiazepin as a premedication
      drug to reduce stress during dental treatment.

PMID- 8865837
TI  - The role of stents in cardiology: advantages and complications.

PMID- 8865838
TI  - Screening children for hypercholesterolemia.

PMID- 8865839
TI  - Necrotizing fasciitis: flesh-eating microbes.

PMID- 8865840
TI  - Ethical issues in military medicine.

PMID- 8865841
TI  - Low dose aspirin and secondary myocardial infarction.

PMID- 8865842
TI  - Visceral leishmaniasis and splenomegaly.

PMID- 8865843
TI  - Incisional hernia via a lateral 5 mm trocar port following laparoscopic
      cholecystectomy.

PMID- 8865844
TI  - Organophosphate poisoning.

PMID- 8865845
TI  - Arthur Schnitzler--poet and physician.

PMID- 8865846
TI  - Diagnosis of longitudinal stress fracture of the tibia with multiplanar CT
      reformats: a case report.

PMID- 8865848
TI  - Expression of cyclin E in colorectal adenomas and adenocarcinomas: correlation
      with expression of Ki-67 antigen and p53 protein.
AB  - The expression of cyclin E in human colorectal adenomas and adenocarcinomas was
      examined immunohistochemically to elucidate the role of cyclin E in the
      colorectal carcinogenesis. The expression of cyclin E was detected in 25%
      (91/358) of the adenomas and 56% (149/267) of the adenocarcinomas. The incidence
      of strongly positive cases was significantly higher in the adenocarcinomas (20%)
      than in the adenomas (5%) (P < 0.01). Among adenomas, a significant correlation
      was noticed between the expression of cyclin E and the grade of atypia. The
      incidence of cyclin E expression was significantly higher in the adenocarcinomas
      without an adenoma component (62%; 104/169) than in those with this component
      (46%; 45/98) (P < 0.05). Furthermore, the incidence of the cyclin E expression
      was higher in stages 1 and 2 carcinoma than in stage 0 and stages 3 and 4
      carcinoma. The expression of cyclin E was the most prominent in tumors invading
      the submucosa and muscularis propria. The expression of cyclin E was
      significantly correlated with the proliferative activity of the tumor cells
      measured by Ki-67 antigen expression (P < 0.01). It was also correlated with the
      expression of p53 protein in the tumor cells (P < 0.01). Overexpression of cyclin
      E and subsequent deregulation of cell cycle may contribute to the development and
      early progression of the colorectal carcinomas.

PMID- 8865847
TI  - Autoimmune hepatitis. Definition--classification--histopathology-
      immunopathogenesis.
AB  - Autoimmune hepatitis (AIH) is a distinct form of acute and chronic inflammatory
      liver disease in which immune reactions against host antigens are found to be the
      major pathological mechanism. If left untreated it carries an unfavourable
      prognosis, and the diagnosis should be made as soon as possible. The diagnostic
      approach has been greatly facilitated by the establishment of a panel of marker
      autoantibodies, which do not define distinct therapeutic groups of AIH, but do
      allow a subgrouping based on differences in patient populations, some clinical
      features and prognosis. The characterization of organ-specific components of the
      liver cell surface as targets of cellular and humoral autoimmune reactions give
      new insights into the pathogenesis of the disease, even though the primary event
      triggering the disease remains to be defined. The most important disease
      promoting factor seems to be a genetically determined background for
      autoimmunity. Without this different environmental factors, including viruses,
      toxins, cytokines and drugs, are only able to induce transient autoimmune
      phenomena and not autoimmune disease. The histopathology of AIH is in keeping
      with the present pathogenetic concept. Although there is no pathognomonic feature
      distinguishing this type of hepatitis from virus-induced forms, some distinct
      morphological lesions are regarded as characteristic. Clinical research on AIH
      has benefited greatly from observations of experimental AIH in mice. Recognition
      of the critical role of autoreactive T-lymphocytes in the pathogenesis and the
      observation of spontaneous recovery from AIH in the animal model associated with
      antigen-specific and antigen-non-specific T-cell suppression have made basic
      contributions to our improved understanding of the natural course of AIH in
      humans.

PMID- 8865849
TI  - Immunohistochemical detection of truncated APC protein in sporadic human
      colorectal adenomas and adenocarcinomas.
AB  - Mutations of the APC gene frequently occur in sporadic forms of colorectal
      adenomas and adenocarcinomas. Phenotypically, the vast majority of these
      mutations result in the truncation of the APC protein. To demonstrate the
      defective APC gene product in human colorectal tumors, rabbit region-specific
      antisera raised against the APC protein of amino acid sequences between 371 and
      390 (SPI) and between 1821 and 1840 (SP3) were used to exhibit the truncated APC
      protein. In all, 86 lesions from 67 cases of sporadic adenoma and adenocarcinoma
      were examined; abnormal staining patterns were distinguished in 43 lesions (50%);
      the incidence of abnormalities was not significantly different between adenomas
      and carcinomas. The majority, 75% exhibited epitopic change with the SPI-positive
      and SP3-negative phenotype (type P1), and 25% exhibited neither of these
      phenotypes (type P2). The staining pattern in all lesions was uniform, and
      studies of carcinomas arising in adenomas showed the same pattern of staining.
      These findings supported the view that the APC lesion is a very early event in
      colorectal carcinogenesis. Furthermore, this simple immunohistochemical approach
      demonstrated that different adenomas from the same patient showed different
      staining patterns.

PMID- 8865850
TI  - Intestinal T-cell lymphoma: a reassessment of cytomorphological and phenotypic
      features in relation to patterns of small bowel remodelling.
AB  - Intestinal T-cell lymphoma (ITCL) is an uncommon entity among primary
      gastrointestinal lymphomas. In this study we evaluated tumours from 20 patients
      presenting with (n = 8) or without (n = 12) a history of coeliac disease (CD).
      Neoplastic lesions were composed of predominantly small (n = 4), small-to-medium
      (n = 2), medium/mixed-to-large (n = 7) or large and anaplastic (n = 7) cells.
      Different patterns of tumour growth and remodelling of the small bowel wall were
      observed. Pattern a (n = 4) was characterized by an intramucosal spread of small
      tumour cells with a small growth fraction. This pattern resembles mucosal
      inflammation in CD. In pattern b (n = 2), ulcerated solitary or multiple tumours
      composed of small to medium-sized cells were observed. The adjacent or distant
      mucosa showed a nearly normal architecture. In pattern c (n = 7), ulcerated
      lesions were composed of medium-sized to large cells. Mucosal flattening occurred
      in all segments infiltrated by lymphoma. In pattern d (n = 7), bowel remodelling
      was observed along the small intestine even at sites not affected by lymphoma.
      The main neoplastic lesions were composed of pleomorphic large or anaplastic
      cells frequently expressing the CD30 molecule. Intramucosal spread of a small
      epitheliotropic T-cell population was observed in the vicinity or even at distant
      segments of the small bowel. The demonstration of clonal rearrangements of T-cell
      receptor genes helped to trace widespread occurrence of this small
      intraepithelial neoplastic component. We suggest that different features of
      tumour cells such as the expression of activation antigens may contribute to the
      remodelling of small bowel mucosa. The addition of immunophenotyping data to
      macroscopic and microscopic features of specimens provided evidence that this
      uncommon lymphoma exhibits a spectrum in cytological composition and growth
      patterns. However, despite the considerable heterogeneity of the cases analysed,
      most of them shared a characteristic immunohistochemical profile (CD3+, CD8+/-,
      CD103+), further substantiating the view that ITCL is the neoplastic equivalent
      of an intraepithelial T-cell subset of the small intestine. This phenotype and
      the intraepithelial accumulation of lymphoma cells observed in the surviving
      mucosa are clues to the diagnosis of this clinicopathological lymphoma entity
      characterized by a broad range of morphological expressions.

PMID- 8865851
TI  - Losses at 3p common deletion sites in subtypes of kidney tumours:
      histopathological correlations.
AB  - Deletions of the short arm of chromosome 3 (3p) have been recognized as
      characteristic features of clear cell renal cell carcinomas (clear cell RCC). We
      analysed 55 clear-cell RCCs and 30 non-clear-cell kidney tumours (10 papillary
      and 7 chromophobic RCCs, 11 oncocytomas and 2 collecting duct carcinomas) in loss
      of heterozygosity (LOH) studies using microsatellite markers for previously
      observed regions of common deletions on 3p in kidney tumours (3p25, 3p21.3,
      3p14.2 and 3p12-13). Alterations were found in all 55 cases of clear-cell RCCs at
      two to four of the 3p regions. Extensive losses were not found in non-clear-cell
      tumours except for collecting duct carcinomas; 1 of 10 papillary RCCs showed
      interstitial deletion limited to a single 3p21.3 locus. LOH analyses using
      microsatellite markers for regions of common deletions at 3p may be of value in
      differential diagnosis of kidney tumours.

PMID- 8865852
TI  - Factor XIIIa-positive dendrocytes and proliferative activity of cutaneous
      cancers.
AB  - Factor XIIIa-positive dendrocytes present at the periphery and inside epithelial
      neoplasms are an heterogeneous group of cells. They are subsets of mesenchymal
      cells, cancer-associated macrophages and antigen-presenting cells. Factor XIIIa,
      other tissue transglutaminases, alpha 2-macroglobulin and tumour necrosis factor
      alpha represent a complex network of mediators influencing tumour progression in
      the skin. In the present study we searched for the presence of dendrocytes and
      alpha 2-macroglobulin deposits inside and in the vicinity of cutaneous carcinomas
      (90 basal cell carcinomas and 46 squamous cell carcinomas) and malignant
      melanomas (69 primary and 28 metastatic tumours). We also studied the
      proliferation of the same neoplasms by Ki-67 immunohistochemistry. Dendrocytes
      were numerous, abutting on and infiltrating most basal cell carcinomas and thin
      malignant melanomas. In contrast, they were present in only low numbers or even
      absent in thick primary malignant melanomas and in their metastases. They
      appeared unmodified around squamous cell carcinomas compared with the surrounding
      skin. Extracellular deposits of alpha 2-macroglobulin were often found in
      locations where dermal dendrocytes were numerous. No correlation was found
      between the Ki-67 indices of carcinomas and the density of peritumoral
      dendrocytes. In contrast, negative relationships were found between the Ki-67
      indices and the number of dendrocytes present inside basal cell carcinomas and
      thin malignant melanomas. This study has yielded circumstantial evidence to link
      the density of factor XIIIa-positive dendritic cells and a low proliferative rate
      of neoplastic cells in basal cell carcinomas and malignant melanomas.

PMID- 8865853
TI  - Endothelial adhesion molecules for nasal-homing T cells in allergy.
AB  - During the allergic reaction mucosal T cells are activated and a local increase
      in numbers occurs. In peripheral blood, a concomitant T cell activation and
      switch towards memory phenotype appears. E-selectin, intercellular adhesion
      molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were studied in
      nasal mucosal biopsies taken during a time-course provocation study, including
      patients with seasonal allergic rhinitis and healthy controls. Allergic patients
      were also studied during the natural pollen season with particular attention to
      the influence of local corticosteroid treatment. Before provocation allergic
      patients and controls did not differ concerning the expression of endothelial
      adhesion molecules. However, the epithelial ICAM-1 expression was increased among
      allergics (P < 0.05). Repetitive allergen provocation induces an increased
      endothelial expression of VCAM-1 in allergic patients (P < 0.01). Similarly, VCAM
      1 expression was increased during the natural pollen season (P < 0.05).
      Interestingly, the increased VCAM-1 expression was inhibited by the use of local
      corticosteroids. The present data demonstrate a putative integrin-VCAM-1
      mechanism for selective homing of T memory cells to the allergic nasal mucosa and
      new in vivo effects of local corticosteroid treatment are demonstrated.

PMID- 8865854
TI  - Pancreatic ischaemic lesions without fat necrosis associated with disseminated
      intravascular coagulation.
AB  - We examined the primary ischaemic changes in the pancreas in 35 patients with
      disseminated intravascular coagulation. In 7 (20%), multiple patchy lesions
      composed of degenerative acinar cells indicating coagulation necrosis were noted.
      None of these lesions was accompanied by fat necrosis. The patchy lesions
      involved the islets of Langerhans in only 1 case. The interlobular arteries of
      the pancreas near these lesions contained fibrin thrombi in all 7 cases. We
      suggest that these lesions, without fat necrosis, are the distinctive ischaemic
      change associated with disseminated intravascular coagulation.

PMID- 8865856
TI  - Acinic cell-like carcinoma of the breast.
AB  - A case of infiltrating carcinoma of the breast with features similar to those
      seen in acinic cell carcinoma of the parotid gland is described in a 42-year-old
      woman. The neoplastic cells were immunoreactive with anti-lysozyme- and anti
      salivary-type amylase antisera and contained electron-dense cytoplasmic globules
      similar to those seen in acinic cell carcinoma of salivary glands. One lymph node
      out of 18 was found to contain a metastatic deposit. The patient is alive and
      well 1 year after mastectomy. This appears to be the first case of carcinoma with
      acinic cell-like features reported in the breast.

PMID- 8865857
TI  - [Safety evaluation of self-contained-self-rescures--carbon dioxide absorption of
      SCSRs under heavy work load].
AB  - The purpose of this study was to evaluate the safety of Self-Contained-Self
      Rescuers (SCSRs) under a heavy work load. Three units, two chemical-oxygen (KO2)
      types and one compressed-oxygen type, were evaluated by a breathing and metabolic
      simulator and by a human subject. The metabolic rate in the simulator tests was
      equivalent to light work; the human subject tests were at a heavy work load. With
      regard to the main physiological stressors imposed by SCSRs, it was found that
      the inhalation temperature under heavy work conditions was able to be estimated
      from the data of the light work condition; the breathing resistance had roughly
      the same relationship under both light and heavy work conditions. On the other
      hand, for the inhaled carbon dioxide, there was no correlation between the two
      conditions. It was found that some SCSRs experienced a rapid increase in inhaled
      carbon dioxide when the metabolic rate of the user exceeded the absorbent
      capacity of the units. In those cases, the user could not continue walking nor
      breathing through the unit. To ensure the safety of the user, we propose that the
      certification standards be changed to include evaluation of carbon dioxide
      absorbent capacity under heavy work load.

PMID- 8865858
TI  - [A study of industrial poisoning from official reports of accident
      investigations].

PMID- 8865855
TI  - Differentiation of pancreatic carcinoma induced by retinoic acid or sodium
      butyrate: a morphological and molecular analysis of four cell lines.
AB  - The antiproliferative and differentiation-inducing effects of all-trans retinoic
      acid (RA) and sodium butyrate (SB) were investigated in four pancreatic ductal
      adenocarcinoma cell lines, two poorly differentiated ones (PT45 and PaTu-II), one
      moderately to poorly differentiated one (Panc-1) and one highly differentiated
      one (A818-1). Treatment with 20 microM RA resulted in moderate inhibition of cell
      growth in all cell lines, but clear evidence of cytodifferentiation (including
      elongated cell processes, increased rough endoplasmic reticulum, intensified
      immunostaining for the mucin marker (M1) was found only in PT45 and Panc-1. These
      phenotypic changes were paralleled by upregulation of RAR (retinoic acid
      receptor)-alpha and -gamma mRNA. SB (1 and 2 mM) treatment inhibited the cell
      growth of all cell lines much more prominently than RA. Cytodifferentiation was
      also largely restricted to PT45 and Panc-1. A noticeable phenomenon was
      enhancement of the expression of the neuroendocrine markers synaptophysin and
      Lcu7 in Panc-1 cells. In conclusion, it is evident that the original
      differentiation status of cells and their responsiveness to the agents are not
      clearly associated, and that RA responsiveness correlates with upregulation of
      RAR-alpha and -gamma mRNA.

PMID- 8865859
TI  - [Effects of age and skin temperature on peripheral nerve conduction velocity--a
      basic study for nerve conduction velocity measurement in worksite].
AB  - The purpose of this study was to investigate the relation between nerve
      conduction velocity (NCV) and some factors which affect the measurement, such as
      age, skin temperature, body build and alcohol consumption. Neurophysiological
      parameters of healthy volunteers (28 males and 27 females, aged 20-57 years) who
      were free from occupational exposure inducing neuropathy were determined by
      monitoring skin temperature. A questionnaire survey on height, alcohol and
      tobacco consumption was also performed. The following results were obtained: 1)
      Analysis of covariance to examine the relation between age groups and NCVs
      adjusting for skin temperature showed significant differences only in peroneal
      motor distal latency (MDL) and duration of sural sensory nerve action potential
      (SNAP) between age groups. However, there was no constant relation between these
      parameters and age. Multiple regression analysis showed the significant
      relationships between age and ulnar MDL and the duration of sural sensory nerve
      action potential, adjusting for sex, height, weight, BMI, alcohol intake
      (frequency/week, ethanol equivalent ml/week), tobacco consumption (/day), skin
      temperature and education years. 2) The skin temperature had significant effects
      on ulnar MDL, ulnar sensory NCV, duration of ulnar SNAP, sural sensory NCV and
      amplitude and duration of sural SNAP according to the results of multiple
      regression analysis and analysis of variance. 3) The body mass index had an
      independent effect on the ulnar nerve conduction, shortening MDL and the duration
      of the sensory nerve action potential. 4) Consumption of alcohol and tobacco had
      no significant relation to nerve conduction velocity in our study. These results
      show that skin temperature is a major covariate of peripheral nerve conduction
      and that it is very important to control skin temperature in studies on nerve
      conduction measurements.

PMID- 8865860
TI  - [Association between dental erosion and exposure to acids in a chemical factory].
AB  - An examination of dental erosion status and a semi-quantitative assessment of
      exposure to acids were carried out for 134 workers in a chemical factory in Osaka
      Prefecture, and an association between the dental erosion and the exposure to
      acids was discussed. 1) Percentage of workers with dental erosion of grade + or
      more among the subjects was 30.6%. 2) Most of the erosion was observed in the
      front teeth. There were more eroded teeth in the upper jaw than in the lower jaw.
      3) The workers were divided into 4 groups according to job type at the time of
      the examination: production, research, clerical work and others. The production
      workers, those routinely handling a large amount of various kinds of acids, was
      the highest proportion of workers with eroded teeth. Because some of the clerical
      workers had previously handled acids, this group of workers included a larger
      number of those with dental erosion than the other two groups. 4) More than half
      of the workers who had been engaged in production had eroded teeth including
      those of grade +/- 5) The intensity of exposure to acids, as a semi-quantitative
      index for cumulative exposure to acids, was calculated in each worker from a
      score for the job type and its duration. A significant association was observed
      between the intensity and the manifestation of dental erosion.

PMID- 8865861
TI  - Species-dependent topography of the peritoneum.
AB  - Planimetric studies of peritoneal surface area were performed in 10 humans, 12
      rabbits, and 15 rats. It was found that the total peritoneal surface area (TPSA)
      correlated in humans with body surface area (BSA) (r = 0.98, p < 0.0001) and body
      weight (r = 0.93, p < 0.001), and correlated in animals with body weight (r =
      0.80, p < 0.005 in rabbits; and r = 0.88, p < 0.0001 in rats). The area of
      parietal peritoneum was 18.1 +/- 1.8% of TPSA in humans, 17.8 +/- 1.0% of TPSA in
      rabbits, and 22.6 +/- 2.1% of TPSA in rats (p < 0.001 vs humans and rabbits).
      Additionally, the area of peritoneum covering the individual organs (expressed as
      % of TPSA) was different in humans, rabbits, and rats: for example, the area of
      peritoneum covering the diaphragm was 6.4 +/- 1.5% of TPSA in humans, which was
      larger than in animals (3.0 +/- 0.3% in rats, p < 0.0001 vs humans and rabbits;
      and only 2.1 +/- 0.4% in rabbits, p < 0.0001 vs humans). Presented results show
      that interspecies variation in the topography of the peritoneum should be taken
      into account when the results from experimental studies done on animals are
      extrapolated to humans.

PMID- 8865862
TI  - In vitro detection of hydrogen peroxide in mesothelial cells.
AB  - Hydrogen peroxide can be indirectly detected in mesothelial cells by measuring
      the rate of inhibition of the intracellular catalase activity by 3-amino-1, 2,3
      triazole (AT). AT binds and inhibits catalase only in the presence of hydrogen
      peroxide, and the effect is proportional to the amount of hydrogen peroxide. The
      effect of AT on catalase activity is prevented in the presence of ethanol. In
      mesothelial cells in vitro exposed to dialysis fluids (Dianeal 1.36%, 2.27%, and
      3.86%) no significantly increased generation of hydrogen peroxide was detected.
      However, interleukin-1 (IL-1) (10 ng/mL) enhances, within two hours (+40%, p <
      0.05), intracellular production of hydrogen peroxide. The presented method of
      detection of intracellular hydrogen peroxide may be helpful in studies of the
      pathomechanisms causing mesothelial damage in conditions of peritoneal dialysis.

PMID- 8865863
TI  - The effects of electrolyte, lactate, high-concentrated glucose, and dialysate on
      peritoneal mesothelial cells.
AB  - In order to investigate which component of dialysate is responsible for
      mesothelial cell damage, we studied the chronic cytotoxicity to mesothelial cells
      by using four types of solution. Four different types of solution (Ringer's
      solution, lactate, high-concentrate glucose, and 4.25% Dianeal) were prepared and
      injected into the abdominal cavity of five ddY-mice, 5 mL every day for one
      month. The monolayer of the mesothelial cells was carefully removed from the
      liver surface by the imprint technique. Then, the mesothelial cell damage was
      evaluated by using trypan blue staining and comparing the results. Trypan blue
      stained cells in 100 mm2 were observed in 7.0% of the control, 15.4% of the
      Ringer's solution, 18.7% of the lactate, 23.2% of the high-concentrate glucose,
      and 22.4% of the 4.25% Dianeal group, respectively. The damaged cells were
      significantly (p < 0.05) greater in the 4.25% Dianeal group than in the control
      group, and those in the high-concentrate glucose group also appeared to be
      greater in number compared to the control group It is concluded from these
      results that damage to the mesothelial cells is induced by chronic exposure to
      high-glucose dialysate, and its pathogenesis is deeply related to high
      concentration of glucose.

PMID- 8865864
TI  - Renal function influences interleukin-8 background production by cultured human
      mesothelial cells.
AB  - Previous studies have demonstrated that mesothelial cells (MC) are important in
      the local host defense system of the peritoneal cavity. Most studies on the
      function of MC are performed on MC derived from material of patients with normal
      renal function (NRF). The aim of the present study was to examine differences in
      interleukin (IL)-8 expression by MC from patients with NRF and from patients with
      end-stage renal disease (ESRD). Therefore, MC were isolated from the omentum and
      pleural exudate of patients with NRF, from spent effluent of stable peritoneal
      dialysis (PD) patients, and from omentum obtained during catheter implantation
      prior to PD treatment. MC were stimulated with increasing doses of IL-1 beta or
      tumor necrosis factor-alpha for 24 hours, after which the supernatant was
      analyzed for IL-8 content. The IL-8 background level of MC isolated from patients
      with NRF was significantly lower than the IL-8 background level of MC derived
      from patients with ESRD. Although IL-8 production appeared to be higher in the
      ESRD MC, this difference was not significant after stimulation. While the overall
      immunity is depressed in uremia, MC are activated. The relatively high background
      of IL-8 might lead to an insensitivity of neutrophils by blocking the receptors
      and explain their impaired chemotaxis in uremia.

PMID- 8865865
TI  - Correlation between effective peritoneal blood flow, blood pressure, and
      peritoneal transfer rates.
AB  - The aim of the studies was an evaluation of the correlation between effective
      peritoneal blood flow (EPBF), blood pressure, and peritoneal transfer during
      intermittent peritoneal dialysis (IPD). In 20 IPD patients it was shown that EPBF
      does not depend on either systolic or diastolic blood pressure. Differences in
      EPBF did not influence peritoneal transfer of small solutes and total protein
      during the first 25 minutes of dwell, but EPBF dependence of transfer was shown
      in the later periods of the dwell. Peritoneal transfer rates were greater with
      higher systolic blood pressure; the significant changes were shown at the
      beginning (for bicarbonate and total carbon dioxide), in the middle (for urea),
      and at the end (for uric acid) of the dwell time. Differences in diastolic
      pressure influenced peritoneal transfer predominantly during the first 25 minutes
      of dwell, although significant changes during the entire dwell were also
      observed. Our results indicate that the influence of both EPBF and blood pressure
      on transport kinetics depends on dwell time: in the first minutes of dwell
      diastolic blood pressure can predominantly contribute to transfer rates, in later
      periods the greater role of EPBF in the determination of transfer rates cannot be
      excluded.

PMID- 8865866
TI  - Effects of bicarbonate dialysis solution on peritoneal transport in rats.
AB  - We studied the effects of bicarbonate dialysis solution (TB 1.36) on the
      peritoneum in our rat model of dialysis. Twenty-four male Sprague-Dawley rats
      were divided into two groups (n = 12 each). One group was dialyzed with standard
      1.36% Dianeal PD-2 (L-group); the other group was dialyzed with TB 1.36 (B
      group). After break-in dialysis after catheter insertion, the animals were
      dialyzed twice daily with 30 mL of the designated dialysis solution for four
      weeks. White blood cell count with differentials and microbiological culture of
      the dialysate were examined once a week to detect peritonitis. A peritoneal
      equilibration test (PET) was performed on the eighth and thirty-sixth days. The
      dialysate was obtained at 0, 2, and 4 hours; a blood sample was taken at 0 hour.
      Peritoneal tissue specimens were obtained after the second PET. Histological
      score was calculated based on the degree of thickening of the peritoneum. Five
      rats in L-group and three rats in B-group suffered from peritonitis. Two other
      rats in B-group had complications and did not complete the experiment. Therefore,
      seven rats from each group finished the experiment, and the PET data was
      analyzed. The peritoneal transport property of B-group did not change over time,
      while, in L-group it became less permeable on the thirty-sixth day. Fibrotic
      thickening of the peritoneum was observed in both groups, however, the
      histological score was slightly lower in B-group. These results suggest that the
      bicarbonate dialysis solution may be less harmful to the peritoneum.

PMID- 8865868
TI  - Plasminogen activator inhibitor-1 and peritoneal transport in peritoneal dialysis
      patients.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is involved in the accumulation of
      extracellular matrix in various tissues. Since peritoneal interstitium is one of
      the resistance sites for transport during peritoneal dialysis (PD), the
      peritoneal PAI-1 level may have a significant effect on peritoneal transport. It
      was the purpose of this study to examine the associations between plasma or
      dialysate PAI-1 levels and the variables of peritoneal transport during
      peritoneal equilibration tests (PET) in 25 stable, adult PD patients. The
      dialysate PAI-1 levels increased with dwell time. Hematocrit was a positive
      predictor of plasma PAI-1 concentration and the change of dialysate PAI-1 amount
      scaled by body surface area (delta DPAI/ BSA). The peritoneal clearance of PAI-1
      was higher than expected for its molecular size, suggesting a local production of
      PAI-1 in peritoneal tissue. The mass transfer coefficient of creatinine scaled by
      BSA (MTCcr/BSA) was a positive predictor of delta D PAI/BSA, suggesting the
      diffusion of plasma PAI-1 into the peritoneal cavity also accounted for part of
      the increased dialysate PAI-1 levels during PET. delta DPAI/BSA was a positive
      predictor of MTC of urea (ur) MTCwr/BSA and MTCcr/BSA, parameters for diffusive
      transport. Our findings are consistent with the hypothesis that peritoneal PAI-1
      level has a significant effect on peritoneal transport during PD.

PMID- 8865867
TI  - Effects of vasodilators on peritoneal solute and fluid transport in rat
      peritoneal dialysis.
AB  - The pharmacological manipulation by vasodilators of peritoneal solutes and fluid
      kinetics was investigated. Rats were dialyzed for 240 minutes with 30 mL 4.25%
      glucose dialysate containing dextran 70. An angiotensin-converting enzyme
      inhibitor (captopril), three calcium channel blockers (nicardipine, diltiazem,
      and verapamil), and an +/-blocker (maxisylite) were administered
      intraperitoneally at various concentrations. Membrane permeability to urea,
      glucose, and protein, actual net ultrafiltration rate (UFR), transcapillary
      ultrafiltration rate (TCUFR), and peritoneal net fluid absorption rate (PNFAR)
      were measured. All three vasodilators caused a decrease in blood pressure, which,
      except for moxisylite, was associated with a decrease in net UFR. Captopril and
      the three calcium antagonists increased PNFAR dose dependently. Captopril
      increased membrane permeability to small and large molecular solutes, with a
      consequent decrease in TCUFR. Nicardipine and verapamil increased permeability to
      urea and glucose but not to protein. Only the latter decreased TCUFR. Diltiazem
      caused no change in permeability. In conclusion, various vasodilators
      administered intraperitoneally affect peritoneal solute and fluid transport
      differently. This should, perhaps, be taken into consideration when working with
      continuous ambulatory peritoneal dialysis (CAPD) patients to whom
      antihypertensive drugs are administered in large doses.

PMID- 8865869
TI  - Discrepancy between solute transport rate and drain volume in CAPD patients with
      ascites.
AB  - The ascites in the chronic renal failure patient is often difficult to treat and
      becomes intractable. Continuous ambulatory peritoneal dialysis (CAPD), as a
      maintenance therapy, is effective in the removal of ascites and may become a good
      alternative in dialysis therapy. The aim of this study was to evaluate the
      peritoneal membrane transport characteristics and ultrafiltration rate in CAPD
      patients who had preexisting ascites. Seven CAPD patients (6 male, 1 female; mean
      age 43 +/- 11 years) were included. The causes of ascites were liver cirrhosis (n
      = 4), hemodialysis-associated process (n = 2), and heart failure (n = 1). A
      peritoneal equilibration test (PET) using 2.5% dialysate was performed by the
      standard method at ten days after starting CAPD. The solute transport rate
      [dialysate glucose ratio (D/D6) and dialysate-to-plasma creatinine concentration
      ratio] showed high (n = 5) or high average (n = 2) transport. In 5 patients with
      high transport, PET showed a discrepancy between solute transport rate and drain
      volume. In spite of the high transport rate, the drain volume was greater than
      expected and corresponded to the area of low average or high average solute
      transport rate. Considering adequate solute clearance and good ultrafiltration,
      CAPD is an effective treatment in end-stage renal disease patients with
      intractable ascites.

PMID- 8865870
TI  - Computerized urea kinetic modeling to prescribe and monitor delivered Kt/V
      (pKt/V, dKt/V) in peritoneal dialysis. Fresenius Randomized Dialysis
      Prescriptions and Clinical Outcome Study (RDP/CO).
AB  - A computerized urea kinetic model of peritoneal urea transport (PACK-PD) has been
      developed and used to calculate prescription parameters which would result in the
      prescribed weekly peritoneal urea clearance (pKpt/V) required to achieve levels
      of weekly summed renal + peritoneal urea clearance (pKprt/ V) targeted at 1.75
      and 2.16. Baseline kinetic data were obtained and analyzed with PACK-PD on 88
      patients, and the program then used these data to calculate the required pKpt/V
      and subsequently the delivered Kpt/V (dKpt/V) from the dialysate collections. A
      total of 108 prescriptions were written and compared to dKpt/V measured over one
      to 24 months in the 88 patients. Both continuous ambulatory peritoneal dialysis
      and automated peritoneal dialysis (APD) were studied (APD consisted of PD+ with
      one or two diurnal and two to four nocturnal cycler exchanges). The correlation
      of dKpt/V to pKpt/V showed r = 0.93 with 95% confidence limits (CL) on agreement
      of +/-20% over a range of pKpt/V 0.52-2.55. The 95% CL on (dKpt/V-pKpt/V) were +/
      0.30. We concluded: (1) that the prescription can be modeled as reliably in
      peritoneal dialysis as in hemodialysis (HD) where dKt/V and pKt/V agree to +/
      25%, (2) that any individual weekly dKpt/V may vary as much as 0.3-0.4 from
      pKpt/V, and (3) that frequent measurement of dKpt/V and adjustment of pKpt/V as
      needed are required (as in HD) to control mean dKpt/V to within +/-10% of mean
      pKpt/V.

PMID- 8865871
TI  - Clinical evaluation of a peritoneal dialysis kinetic modeling set.
AB  - A closed system kinetic modeling set (KMS) has been fabricated which permits
      collection of a small 100-mL aliquot from each exchange. The KMS was used to
      collect aliquots from 65 exchanges in 13 patients. The concentrations of urea
      nitrogen (UN), creatinine (Cr), glucose (G), and total protein (TP) were measured
      in each individual aliquot (Cka) and drain bag (Cba), and all aliquots for each
      dialysis treatment were used to calculate the concentrations expected in total
      batched dialysate (BaC) for the treatment and were compared to the measured
      concentrations (BaM) in mixed total dialysate. The ratios Cka/Cba [mean+/- two
      times coefficient of variation (mean +/- 2CV)] were 1.00 +/- 5%, 1.00 +/- 5%,
      1.01 +/- 10%, and 1.00 +/- 6%, respectively, for UN, Cr, G, and TP (each, n =
      61). The ratios BaC/BaM (mean +/- 2CV) were 1.00 +/- 2%, 1.00 +/- 5%, 1.01 +/-
      3%, and 0.99 +/- 5%, respectively, for UN, Cr, G, and TP (each, n = 15). We
      concluded that the KMS aliquots can be reliably used for kinetic and total
      clearance calculations without mixing and transporting large volumes of
      dialysate.

PMID- 8865873
TI  - Peritoneal dialysis solution attenuates microvascular leukocyte adhesion induced
      by nitric oxide synthesis inhibition.
AB  - In the mesenteric microcirculation, inhibition of nitric oxide (NO) synthesis
      results in an inflammatory response through increased leukocyte adherence to the
      microvascular postcapillary venular endothelium. Recent studies have demonstrated
      that elevated concentrations of endogenous NO synthesis inhibitors are present in
      renal failure. How peritoneal dialysis solutions may affect leukocyte-endothelial
      interactions during inflammation induced by NO synthesis inhibition has been
      previously unknown. Using in vivo intravital microscopy of the rat mesenteric
      postcapillary venules, microvascular leukocyte adherence was quantitated during
      baseline conditions in which the mesentery was superfused with a buffer solution,
      followed by the superfusion of a NO synthesis inhibitor NG-nitro-L-ARGININE
      methyl ester (L-NAME) added to the buffer, followed by 4.25% Dianeal (4.25% D).
      When compared to baseline, L-NAME increased the mean number of adherent
      leukocytes by fivefold (2.2 +/- 0.9 vs 11.6 +/- 3.6 leukocytes/100 microns
      venule/10 min, p < 0.05), while 4.25% D quickly reversed the L-NAME-induced
      inflammatory response, returning the number of adherent leukocytes back to
      baseline values (11.6 +/- 3.6 vs 2.4 +/- 1.3 leukocytes/100 microns venule/ 10
      min, p < 0.05). These results confirm that NO synthesis inhibition induces
      inflammation in mesenteric postcapillary venules. Superfusion of 4.25% D reverses
      leukocyte adhesion induced by NO synthesis inhibition. Thus, a standard
      peritoneal dialysis solution (4.25% D) reverses the leukocyte-adhesive effects of
      NO synthesis inhibition in the mesenteric microcirculation.

PMID- 8865872
TI  - Peritoneal functional changes induced by dialysate containing bicarbonate instead
      of lactate.
AB  - Lactate (L)-containing dialysate has a low pH, responsible for its poor
      biocompatibility. Dial-ysate-containing bicarbonate (B) with a physiological pH
      is available. We compare the peritoneal functional effects of these two
      solutions. Eight patients were studied two weeks apart using two consecutive
      peritoneal kinetic tests to determine convective and diffusive mass transfer
      coefficient (MTC) capacities for different solutes. Both L and B solutions were
      identical, except for pH and buffer content. Peritoneal equilibration values at
      four-hour dwell time were similar for all solutes, except for urea (B: 0.91 +/-
      0.05 vs L: 0.87 +/- 0.06, p < 0.05). Peritoneal MTC (B vs L) values for urea
      (19.6 +/- 6.6 vs 18.2 +/- 4.5), creatinine (8.8 +/- 4.8 vs 7.8 +/- 3.5),
      phosphate (7.7 +/- 4.6 vs 6.0 +/- 2.2), and potassium (13.3 +/- 5.6 vs 11.7 +/-
      5.0) were slightly higher for B (NS). Glucose-MTC was slightly lower for B (6.2
      +/- 3.3 vs 7.5 +/- 3.2, NS). Ultrafiltration (UF) was lower for B (drained
      volume: 2120 +/- 204 vs 2443 +/- 285 mL after 4 hr, p < 0.05). Higher
      transperitoneal calcium [11 +/- 22 L vs -3.1 +/- 11.0 (positive balance) mg, p <
      0.05] and sodium (48 +/- 30 L vs 13 +/- 20 mEq) removal were evident. With L, the
      loss of 43.0 +/- 6.3 mEq of bicarbonate appeared. The linear regression analysis
      of MTC values showed higher r coefficients for the bicarbonate solution. These
      results suggest that bicarbonate dial-ysate improves the diffusion capacity of
      the peritoneum with respect to lactate.

PMID- 8865874
TI  - Cytotoxicity, pH, and glucose degradation products in four different brands of PD
      fluid.
AB  - This study was undertaken in order to evaluate differences in pH, cytotoxicity,
      and concentration of glucose degradation products between different peritoneal
      dialysis (PD) fluids. Four brands of commercial PD fluids were selected:
      Gambrosol, Bieffe, Dianeal, and Lock-olys, with a glucose concentration between
      3.86% and 4.25%. The cytotoxicity of unused PD fluid was measured as inhibition
      of cell growth after three days' exposure of a fibroblast cell line using neutral
      red vital stain. The concentration of 2-furaldehyde, 5-hydroxymethyl-furaldehyde
      (5-HMF), acetaldehyde, formaldehyde, glyoxal, and methylglyoxal was analyzed by
      high-performance liquid chromatography technique. All the investigated PD fluids
      were cytotoxic and contained noticeable amounts of aldehydes. No major
      differences were observed in pH, although one fluid with a slightly lower pH was
      found to be less cytotoxic. This fluid also contained less formaldehyde,
      acetaldehyde, methylglyoxal, and glyoxal but instead contained more 5-HMF. We
      conclude that all brands of PD fluid are cytotoxic due to glucose degradation
      products and that they contain noticeable concentrations of low-molecular
      aldehydes. Our results also demonstrate that the concentration of 5-HMF, used as
      a regulatory control of PD fluids, does not correlate well with cytotoxicity.

PMID- 8865875
TI  - Pharmacokinetic analysis of creatinine generation discrepancy as an index of
      noncompliance in CAPD.
AB  - The limitations of the ratio of estimated-over-predicted creatinine generation
      (E/P) as an index of noncompliance were investigated in hypothetical continuous
      ambulatory peritoneal dialysis (CAPD) populations with steady-state E/ P ranging
      between 0.5 and 1.5 (mean 1.0), anuria or urine creatinine clearance of 50 L
      weekly, and omission during the noncompliant state of one, two, or three daily
      exchanges from a schedule of four daily exchanges, which would provide, in the
      compliant state, a peritoneal creatinine clearance of 50 L weekly. Standard
      pharmacokinetic methods were applied to estimate both serum creatinine
      concentration at the end of the first 24-hour period after resumption of the
      schedule with four daily exchanges and the amount of creatinine lost from the
      body in the same nonsteady-state period. The shift of the E/P frequency
      distribution curve to higher values between the steady and nonsteady states was
      sufficient to create a clear separation of these curves only in anuria with three
      exchange daily noncompliance (nonsteady state: E/P 1.02 - 3.04, with a mean of
      2.03). In all other cases, the shift of the E/P curve was small and did not
      create a clear separation of the E/P frequency distribution curves. Because of
      the wide variation of the E/P values in the steady state and the relatively small
      shift of E/P distribution to higher values in the nonsteady state after a sudden
      increase in total creatinine clearance, E/P is not a suitable test for
      noncompliance in cross-sectional studies.

PMID- 8865876
TI  - Circulating burst-forming unit-erythroid (BFU-E) colonies as an early marker to
      measure the recombinant human erythropoietin response in peritoneal dialysis
      patients.
AB  - To evaluate circulating burst-forming unit-erythroid (BFU-E) cells after
      erythropoietin (EPO) treatment, 7 female continuous ambulatory peritoneal
      dialysis patients were studied [baseline hemoglobin (HB): 7-10.5 g/dL)]. EPO
      (4000 U subcutaneously) was administered twice weekly for two months. The control
      group consisted of 7 healthy women with similar demographic characteristics.
      Mononuclear cells (MC) (5 x 10(5)) were added to 1 mL of culture medium,
      supplemented with 30% fetal bovine serum, 2 U/mL of EPO, 1% bovine serum albumin,
      and 0.3% agar. To enumerate colonies derived from each circulating BFU-E, plates
      were examined by inverse light microscopy, identifying BFU-E as large aggregates
      with more than 100 hemoglobinized cells (HC). A remarkable individual response
      was observed, with Hb values ranging 8.4-13.6 g/dL at week 4 and 8.8-16.5 g/dL at
      week 8. Baseline levels of BFU-E in patients ranged 0-100/5 x 10(5) MC (0-358 mL
      of whole blood), and in controls they ranged 6-24/5 x 10(5) MC (29.6-101.3/mL)
      (NS). Hemoglobin levels after four and eight weeks of EPO showed a significant
      relationship with circulating BFU-E at baseline (r = -0.873, r = -0.928,
      respectively). The increment in Hb after eight weeks showed a significant
      relationship with baseline BFU-E (r = 0.812). Hemoglobin levels at the fourth to
      eighth week, and the increment in Hb after eight weeks, showed a significant,
      direct relationship with the increments in circulating BFU-E registered after one
      to two weeks of treatment. We conclude that, after the first week of EPO
      treatment, its effect on hemoglobin may be predieted by the increment in
      circulating BFU-E. Thus; a new tool to measure the earliest EPO effects has
      become available.

PMID- 8865877
TI  - Serum insulin and insulin-like growth factor binding protein-1 levels in adult
      patients undergoing peritoneal dialysis.
AB  - It is known that serum insulin-like growth factor binding protein-1 (IGFBP-1)
      concentrations are inversely related to insulin levels both in healthy and
      diabetic subjects. The aim of the present study was to assess serum IGFBP-1
      levels in a group of patients undergoing peritoneal dialysis (PD) and to evaluate
      their relationship with serum insulin concentrations. Thirty-five patients [19
      males, 16 females; age (mean +/- SEM) 53.2 +/- 2.5 years; range 18-78; duration
      of continuous ambulatory peritoneal dialysis 33.1 +/- 6.0 months; Kt/V 2.00 +/-
      0.05; normalized protein catabolic rate 1.00 +/- 0.05 g/kg/day] were studied.
      Nine patients were diabetics. In all patients, baseline IGFBP-1, insulin, and
      growth hormone (GH) levels were determined. Fasting IGFBP-1 levels were elevated
      in 19 (54%) patients and were normal in 16 patients. In all patients, high levels
      of serum insulin levels (> 25 microU/mL) were observed. Baseline IGFBP-1 levels
      were only slightly higher in diabetic patients (53.7 +/- 14.6 vs 40.5 +/- 8.2
      micrograms/L,NS), however, serum levels of GH were similar in both groups (3.0 +/
      1.8 vs 2.9 +/- 0.5 microgram/L, NS). There was no correlation between fasting
      insulin and IGFBP-1 levels both in the whole group (r = 0.2; NS) and the diabetic
      (r = 0.2; NS) and nondiabetic (r = 0.3; NS) subgroups, despite high fasting
      insulin levels. We could only find a significant positive correlation between
      fasting glucose and IGFBP-1 levels in the diabetic group (r = 0.7, p < 0.05). Our
      data suggest that adult patients undergoing PD show hyperinsulinemia associated
      with normal or high serum IGFBP-1 levels. This suggests that insulin does not
      affect IGFBP-1 production in this group of patients. It could be explained, at
      least in part, by the insulin resistance present in uremia.

PMID- 8865878
TI  - Comparison of long-term survival between hemodialysis and peritoneal dialysis.
AB  - We have reviewed the literature and our own center's results for patients on long
      term continuous ambulatory peritoneal dialysis (CAPD) in comparison to results
      for patients on hemodialysis (HD). Contrary to recent American data showing one
      year survivals to be worse on CAPD, the Canadian Registry and other studies show
      no significant difference in survivals on the two methods. Results are also
      conflicting for diabetics. Insufficient adjustments for age and case-mix
      variations are probably the most important causes for differences. For the
      general population, personal Cox-adjusted data show no difference between CAPD
      and HD up to ten-year follow-up, with very close curves for the adults and non
      significant differences for the elderly. Old elderly (> 75 years) have better
      survival on CAPD in the first years of treatment. Dropout, which is higher on
      CAPD, decreases with age, and the patient retention on CAPD is worse than on HD
      for all patients, except the old elderly, for whom it is similar. These data were
      obtained in patients receiving a standard treatment, modified in order to give a
      more adequate dialysis dose only in recent years. The results of a prospective
      three-year study on the effect of nutritional [serum albumin and transferrin,
      normalized protein catabolic rate (PCRN), and subjective global assessment of
      malnutrition] and adequacy indices [Kt/V, creatinine clearance (Ccr), residual
      renal function] on patient survival on CAPD and HD are reported. Survival was not
      different for the two methods. Using the Cox analysis, nutritional indices did
      not affect survival whereas adequacy indices did. The effect of low serum albumin
      on survival was referable to the predialysis nutritional state. The similar
      survivals obtained on CAPD and HD, with Kt/V more or less than 1.0/treatment for
      HD and 1.7/week for CAPD, support the "peak concentration hypothesis" of
      Keshaviah et al. Survival in different groups of patients with different Kt/V and
      Ccr shows that the adequate dose on CAPD is Kt/V between 1.96 and 2.03 and Ccr >
      or = 70 L/week. A group of 26 patients who remained on CAPD treatment for more
      than eight years was also studied. Patient age and predialysis comorbidity were
      the most important factors affecting survival. Patients surviving longest had > 3
      g/dL of serum albumin, > 0.8 g/kg/day of PCRN, a Kt/V > 1.6, and a weekly Ccr >
      54L/week.

PMID- 8865879
TI  - Is peritoneal dialysis the preferred modality in the diabetic patient?
AB  - There has been much debate recently whether peritoneal dialysis is an acceptable
      modality of renal replacement therapy in the diabetic patient. The authors review
      the recent continuous ambulatory peritoneal dialysis (CAPD) mortality literature
      and suggest that mortality can be improved by increasing the quantity of
      peritoneal dialysis delivered. The major disadvantages and advantages of CAPD are
      reviewed and presented. Peritoneal dialysis remains a viable modality of renal
      replacement therapy in the appropriate diabetic patient provided an adequate dose
      of dialysis is maintained.

PMID- 8865880
TI  - The economic cost of dialysis: a comparison between peritoneal dialysis and in
      center hemodialysis in a Spanish unit.
AB  - We have studied the economic cost of dialysis therapy in our area (public
      setting) during 1994, comparing the cost of different modalities of in-center
      hemodialysis (HD) and home peritoneal dialysis (PD). Analyzed costs included:
      personnel, drug expenditure, disposable (dialysis- and non-dialysis-related),
      laboratory, other services, indirect costs, maintenance and redemption, hospital
      admissions, transport, and home supplies. The final cost per patient and year (in
      1994 US$) was: hemodiafiltration (AN69 filter, bicarbonate buffer) $58,890; HD
      polymethylmethacrylate filter and bicarbonate buffer $55,076; HD cuprophane and
      acetate buffer $49,767; CAPD $31,201; and cost of automated PD $42,519. The main
      expenditure sections were: home supply and hospital admissions for PD patients,
      and personnel, drug expenditures, disposable dialysis material, indirect costs,
      hospital admissions, and transport for HD patients. Home peritoneal dialysis
      therapy has a significantly lower economic cost than any in-center HD modality.

PMID- 8865881
TI  - Similarities in functional state of the kidney in patients treated with CAPD and
      hemodialysis.
AB  - Differences have been reported in the decline of residual renal function in
      patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis
      (HD), but it is unknown whether the urinary handling of water and solutes is
      similar in these patient groups. Ten CAPD patients with residual renal function
      were investigated during a clearance period (CP) of 24 hours, and 11 HD patients
      were investigated during one interdialytic interval of three days. In CAPD
      patients the urinary volume excretion was 0.65 +/- 0.31 mL/min (mean +/- SD), and
      the inulin clearance was 3.85 +/- 2.82 mL/min. A negative correlation was found
      between the peritoneal net ultrafiltration rate and both the urinary volume
      excretion rate (r = -0.80, p < 0.01) and the fractional sodium clearance (r = 
      0.69, p < 0.05). In HD patients the urinary volume excretion increased from 0.36
      +/- 0.36 mL/min during the initial eight hours of CP (HD-A) to 0.64 +/- 0.29
      mL/min during the last ten hours of CP (HD-D, p < 0.05), and the inulin clearance
      increased from 1.9 +/- 1.3 (HD-A) to 2.9 +/- 1.1 (HD-D, p < 0.005). The
      fractional sodium clearance increased from 8.5 +/- 5.7% (HD-A) to 14.4 +/- 9.0%
      (HD-D, p < 0.05). It can be concluded that the fractional excretion of volume and
      fractional clearance of solutes were similar in patients treated with CAPD and
      hemodialysis. The most important regulating factor seems to be the volume status
      influenced by volume removal by peritoneal net ultrafiltration in CAPD patients,
      and volume expansion during the interdialytic interval in hemodialysis patients.

PMID- 8865882
TI  - Delayed graft function after renal transplantation in patients undergoing
      peritoneal dialysis and hemodialysis.
AB  - We have compared the incidence of delayed graft function (DGF) after renal
      transplantation in our patients undergoing peritoneal dialysis (PD) (group A, n =
      92) or hemodialysis (HD) (group B, n = 587), analyzing the prevalence of the main
      risk factors for DGF in both groups. Both groups were comparable, except for a
      higher prevalence of diabetes (p < 0.05) and a shorter time on dialysis (p <
      0.01) in group A. Immediate graft function occurred in 68.5% of group A and 46.5%
      of group B, DGF in 22.5% of group A and 39.5% of group B, and there was never any
      function in 9% of group A and 14% of group B (p < 0.001). When potential risk
      factors for DGF were compared, no relevant differences could be found. HD was
      performed more frequently immediately before surgery in group B (p < 0.001), but
      statistical analysis showed no impact of this measure on the incidence of DGF. In
      conclusion, in our population, patients on PD present higher rates of immediate
      graft function after renal transplantation than patients on HD. The explanation
      for the difference is not clear, but seems to be related to the dialysis modality
      itself, as the profile of risk factors for DGF is very similar in both
      populations.

PMID- 8865883
TI  - High flux peritoneal membrane is a risk factor in survival of CAPD treatment.
AB  - A high dropout rate is a major problem of continuous ambulatory peritoneal
      dialysis (CAPD) treatment. Serum albumin is both a significant parameter of
      dropout in CAPD and a predictor of peritoneal transport category based on the
      peritoneal equilibration test (PET). High flux peritoneal membrane (HFPM) may
      lose more protein in the dialysate. We examined the effect of HFPM on the
      survival of treatment of CAPD. The study was composed of 171 adult patients who
      had standard PET. The peritoneal transport category was based on their first PET
      after starting CAPD. The HFPM was defined as the dialysate-to-plasma creatinine
      concentration ratio (D/P) of more than one standard deviation of the mean (0.702
      +/- 0.114; D/P > 0.816). Twenty-two patients had HFPM. The other 149 patients
      were categorized as the non-high flux group. The high flux group had a
      significantly lower serum albumin at PET (3.07 +/- 0.15 vs 3.68 +/- 0.05 g/dL,
      respectively p < 0.0001) and lower mean serum albumin during treatment than the
      non-high flux group (3.40 +/- 0.20 vs 3.70 +/- 0.04 g/dL, respectively, p =
      0.020), and lower net drainage volume (p = 0.0007), but age, diabetes, total
      Kt/V, and total normalized weekly creatinine clearance were not different between
      groups. The risk of dropout was higher in the high flux group (p = 0.0127, Cox
      Mantel log rank test), and the risk increased, especially after 1.5 years of
      treatment. Corrected for other risk factors, patients who had HFPM have two times
      the risk of dropout compared to the non-high flux groups (p = 0.0401, Cox
      proportional hazards model).

PMID- 8865884
TI  - Cardiovascular factors influencing survival in dialysis patients.
AB  - Cardiovascular disease is the most common cause of death among dialysis patients.
      Cardiovascular abnormalities that predispose to mortality include acute
      myocardial infarction, chronic ischemic heart disease, atherosclerotic peripheral
      vascular disease, congestive heart failure, left ventricular hypertrophy, dilated
      cardiomyopathy, hypertrophic hyperkinetic heart disease, prior cardiac arrest,
      and possibly systemic hypertension. This review explores the influences of
      cardiovascular disease on survival in patients with end-stage renal disease
      treated with dialysis.

PMID- 8865885
TI  - Cardiovascular risk factors in diabetic patients undergoing continuous ambulatory
      peritoneal dialysis.
AB  - To determine the impact of continuous ambulatory peritoneal dialysis (CAPD) on
      cardiovascular risk factors in diabetic patients, we evaluated serum lipid
      profiles and plasma levels of coagulation and fibrinolysis parameters in 23
      diabetic patients on long-term CAPD (aged 55 +/- 14 years, mean +/- SD), and
      compared them with those of diabetic patients undergoing hemodialysis (n = 62, 56
      +/- 10 years) or kidney transplantation (n = 14, 43 +/- 14 years), and 40 normal
      subjects (39 +/- 10 years). All of the parameters were compared using analysis of
      covariance to adjust for the difference in age among the four groups in males and
      females separately. In the male CAPD patients, there were no significant
      differences in the serum concentrations of lipids, lipoproteins, and
      apolipoproteins. In contrast, in the female CAPD patients, the levels of
      triglyceride and apolipoprotein (apo) B and the low-density lipoprotein (LDL)
      cholesterol/ high-density lipoprotein (HDL) cholesterol ratio were significantly
      higher than those in the normal females. Lipoprotein (a) did not differ
      significantly among the four male and female groups. The plasma levels of
      fibrinogen and von Willebrand factor were higher both in the male and in the
      female CAPD patients than in the other corresponding groups. There was no
      significant difference in the levels of plasminogen activator inhibitor-1 among
      the four groups. In conclusion, CAPD is associated with a more atherogenic lipid
      profile than are hemodialysis and kidney transplantation in female diabetic
      patients, but not in male diabetic patients. Both male and female diabetic
      patients on CAPD have a hypercoagulability state but not a decreased fibrinolysis
      state.

PMID- 8865886
TI  - Successful use of continuous ambulatory peritoneal dialysis in octogenarians.
AB  - Clinical data and outcomes of 18 patients, aged 80 or older, on continuous
      ambulatory peritoneal dialysis (CAPD) during the last five years were reviewed.
      There were 12 males and 6 females, with a mean age of 85 (range 82-91 years) and
      median duration on CAPD of 31.5 months (range 2-58 months). End-stage renal
      disease was caused by nephrosclerosis in 9, diabetes mellitus and light chain
      disease in 2 each, and chronic glomerulonephritis, membranous nephropathy, and
      IgA nephropathy in 1 each, with the cause unknown in yet another 2 patients.
      Hypertension and angina were the commonest comorbid conditions observed.
      Peritonitis episodes occurred one per 10.8 patient-months, and necessitated
      catheter removal in 7 patients and reinsertion in 6 of them. Fourteen episodes of
      exit-site infections were seen in 8 patients, 2 developed pericatheter leak, and
      1 had tunnel infection. Nine patients are continuing CAPD successfully, with a
      median duration of 29 months (range 11-57 months). One patient was transferred to
      hemodialysis, and 8 died. The causes of death were peritonitis (3/8),
      cerebrovascular accident (2/8), pneumonia (1/8), and septicemia (1/8), with the
      cause not known in 1 patient. Our survival rate of 80% at three years is
      encouraging, and we advocate CAPD as a successful alternative treatment modality
      in octogenarians.

PMID- 8865887
TI  - Benefits of a multidisciplinary predialysis program in maintaining employment
      among patients on home dialysis.
AB  - We evaluated the benefits of a multidisciplinary predialysis intervention to help
      home dialysis patients maintain employment. This program was shown to be
      successful with in-center hemodialysis patients in a case-controlled study
      published in the American Journal of Kidney Disease in September, 1993. We looked
      at 30 patients on home dialysis (28 on continuous ambulatory peritoneal dialysis
      and 2 on home hemodialysis) as of March, 1995. The age of the patients ranged
      from 28 to 63 years, with a mean of 46.8 years. Forty-three percent of the
      patients were diabetic. The patients went through a multidisciplinary predialysis
      program which consisted of: (1) psychosocial assessment, (2) education about
      dialysis and choice of modalities, (3) orientation to dialysis unit, and (4)
      counseling sessions with patient, significant family members, and others. During
      this time, patients were referred to the program approximately six months before
      beginning dialysis. There was continued collaboration among members of the
      multidisciplinary team. Of the 30 patients, 11 were already disabled when
      beginning dialysis. Of the 19 who were working once dialysis began, 14 maintained
      employment (3 diabetic), with 1 retiring and 4 becoming disabled. Therefore, 74%
      of patients maintained employment. In conclusion, employment was maintained by
      this predialysis multidisciplinary program.

PMID- 8865888
TI  - Designing dialysis prescriptions.
AB  - Our objective was to determine the adequacy of dialysis in our patients currently
      on home peritoneal dialysis and develop a program of surveillance aimed at
      maintaining tKt/V (Kt/V calculated from peritoneal clearance and residual renal
      function) greater than 2.0 as recommended by the CANUSA study. Eighty-nine
      patients were entered into our study between September, 1993 and September, 1995.
      Initial dialysate volumes used during the training period were determined by
      using a patient-specific protocol. Two weeks after discharge a standard
      peritoneal equilibration test was performed to determine total Kt/V using a
      computer program, and dialysis prescriptions were changed to achieve a tKt/V >
      2.0 in those patients who had tKt/V < 2.0, and those with tKt/V > 2.0 were
      followed without further intervention. Of the patients who had initial
      assessments, 33.7% had tKt/V of 1.65 and 66.3% had tKt/V of 2.46, and the
      difference was mainly due to residual renal function. Forty-four patients were
      started on continuous ambulatory peritoneal dialysis (CAPD), of whom 34% had
      tKt/V < 2.0 and 66% had tKt/V > 2.0, and of the 36 patients on continuous cycling
      peritoneal dialysis (CCPD), 30.5% had tKt/V < 2.0 and 69.5% had tKt/V > 2.0. The
      cost of changing dialysis prescriptions is less with CCPD than with CAPD, and a
      0.8-1.0 L increase in dialysate volume will increase peritoneal Kt/V (dKt/V) by
      0.1 on average. Patients weighing less than 53 kg can achieve a dKt/V > 2.0 even
      in the absence of residual renal function, but as body weight increases there is
      greater dependence on residual renal function to achieve adequate dialysis. We
      have been able to maintain patients on adequate dialysis (tKt/V > 2.0) by
      checking peritoneal clearance and residual renal function initially and on a
      regular basis. Whether a tKt/V > 2.0 will be sufficient to maintain health and
      well-being of our patients will require a longer period of observation.

PMID- 8865890
TI  - Total clearance and extracellular volume with 125I-iothalamate in peritoneal
      dialysis.
AB  - To assess treatment adequacy by calculating total clearance (CL) in patients on
      peritoneal dialysis (PD), fluids must be collected over 24 hours, a laborious
      procedure and prone to inaccuracy. CL calculation from the plasma disappearance
      curve of an injected tracer has none of the above inconveniences. We therefore
      compared creatinine clearance CR-CL with CL calculated from the plasma
      disappearance curve of 125I-iothalamate (IO) injected in a single intravenous
      bolus. Twelve patients aged 63 (44-80) years and on PD for four (1-44) months
      were studied in hospital. Nine plasma samples were taken for IO-CL after a bolus
      of 21 kBq/kg of tracer. The least-squares biexponential fitting according to
      Gauss-Newton-Raphson was then carried out: [Aexp(-at) + Bexp(-bt)], and clearance
      was calculated by the formula, IO-CL = dose/AUC, where AUC = A/a + B/b. Both CLs
      were normalized for 1.73 m2 of body surface. Agreement (r = 0.746, p = 0.005) for
      the CR-CL (6.8 +/- 1.9 mL/min) and IO-CL (7.6 +/- 1.9 mL/min) was good, with a
      difference of 0.9 +/- 1.4 mL/min (t = 2.182, p = 0.052). Extracellular volume
      (ECV), calculated from the IO plasma disappearance curve with the formula, ECV =
      dose/ bAUC, and including the endoperitoneal fluid, was 19.8 +/- 2.9 L (29.5 +/-
      6.2% body weight).

PMID- 8865891
TI  - Management of pregnancy in women undergoing continuous ambulatory peritoneal
      dialysis.
AB  - A survey in which there were responses from dialysis units caring for
      approximately 38% of women aged 14-44 receiving continuous ambulatory peritoneal
      dialysis in the United States revealed a conception rate of 0.2% per year. A
      total of 44 pregnancies were identified in women treated with peritoneal dialysis
      at some time during their pregnancies. Two thirds of pregnancies were complicated
      by hypertension and one third by severe hypertension. There was little difficulty
      with catheter placement during pregnancy, and peritonitis was an unusual
      complication, which did not result in fetal loss. Forty-eight percent of
      pregnancies resulted in surviving infants. All but one were premature and two
      thirds were small for gestational age.

PMID- 8865889
TI  - Estimating urea volume in amputees on peritoneal dialysis by modified
      anthropometric formulas.
AB  - Body composition determines body water content (the fraction body water/body
      weight). With developing obesity, body weight and body water increase, but body
      water content decreases. The anthropometric formulas for urea volume (body water)
      for Kt/V computations in nonamputated peritoneal dialysis subjects reflect this
      fundamental rule of body composition. However, the use of uncorrected
      anthropometric formulas in amputees provides body water content estimates
      inconsistent with the estimates of body composition obtained from nutritional
      assessment. Corrected estimates of urea volume can be obtained in three steps:
      (1) The non-amputated weight at the same body composition is computed by dividing
      the weight at the urea kinetic study (postamputation) by (1-the fractional weight
      loss from the amputation); (2) body water and body water content at this
      nonamputated weight are obtained from the appropriate anthropometric formula; (3)
      at the time of the urea kinetic study, post-amputation, body water is equal to
      the estimate of body water content obtained from step 2 times the body weight at
      the urea kinetic study. The corrected estimates of urea volume provide body water
      content values agreeing with the estimates from nutritional assessment.

PMID- 8865892
TI  - Less infusion pain and elevated level of cancer antigen 125 by the use of a new
      and more biocompatible PD fluid.
AB  - Our objective was to investigate the clinical effect of a less toxic and less
      acidic peritoneal dialysis (PD) fluid produced in a two-compartment bag (PD-Bio).
      The study had an open cross-over design in 4 stable patients, where the patient
      served as his/her own control. After a period of three months using conventional
      PD fluid the patients were switched to three months on the new PD fluid. Routine
      blood chemistry and transport characteristics were measured. Cell samples from
      overnight spent dialysis fluid were analyzed for viability, differential count,
      release of superoxide radicals, and cancer antigen 125 (CA 125). Subjective
      patient symptoms and handling properties were investigated by a patient
      questionnaire. Cancer antigen 125 increased significantly, and patients with
      discomfort or infusion pain during the control period improved during the PD-Bio
      period. Patient acceptance with respect to handling of the two-compartment bag
      was excellent and did not differ from the use of standard bags. No changes were
      seen in the cell samples from spent dialysate, blood chemistry, or transport
      characteristics between the two treatment periods. PH in the effluent dialysate
      was, however, significantly higher for PD-Bio at all times during the two-hour
      dwell. Our results suggest that a PD fluid produced to minimize the level of
      toxic glucose degradation products and to obtain a more physiological pH has an
      impact on CA 125 levels, reduces pain and discomfort in connection with infusion
      of fluid, and does not influence the transport characteristics.

PMID- 8865894
TI  - Prevalence and epidemiology of hepatitis C infection in patients on peritoneal
      dialysis in France. French PD centers.
AB  - We performed a cross-sectional study to establish the hepatitis C virus (HCV)
      serologic status for all French patients undergoing peritoneal dialysis (PD) on
      January 1, 1995. We listed a total of 1508 patients, and the exhaustiveness rate
      was about of 75% of the whole French PD population treated at this date. Only 47
      of the 1508 patients were anti-HCV positive (HCV+): the global HCV prevalence was
      3.12%. HCV+ patients were treated by PD for a longer time than HCV-patients (4 +/
      4 vs 2 +/- 2 years; p < 0.001); 89% of the HCV+ patients received blood
      transfusions; 60% had been previously treated by hemodialysis, and 26% previously
      received a kidney transplantation. In 49% of the HCV+ patients, HCV antibodies
      were discovered before the start of the peritoneal dialysis program, and a
      seroconversion was observed in only 4 (0.27%) of them during the PD treatment.
      All these patients received blood transfusion. In patients without past history
      of hemodialysis or transplantation (exclusively treated by PD), HCV prevalence
      was 1.5%, not far off that of the general population. Peritoneal dialysis seems
      not to be an additional risk factor for hepatitis C infection in France.

PMID- 8865893
TI  - Efficacy of bolus intravenous iron dextran treatment in peritoneal dialysis
      patients receiving recombinant human erythropoietin.
AB  - The efficient use of recombinant human erythropoietin (rHuEPO) requires adequate
      body stores of iron. In peritoneal dialysis (PD) patients, iron replacement is
      most commonly administered orally. In this study, we prospectively followed 7
      stable PD patients following bolus intravenous infusion of 1 g iron dextran in an
      outpatient setting. At 12 weeks, significant (p < 0.05) increments in mean
      hematocrit from 29.13% to 34.85%, transferrin saturation from 10.15% to 29.33%,
      serum iron from 27.38 to 67.00 micrograms/dL, and serum ferritin from 150.30 to
      331.40 ng/mL were observed. Post-treatment, there was less requirement of rHuEPO,
      and at six months there was a 26% reduction in the mean weekly subcutaneous
      rHuEPO dose. At 12 weeks, serum albumin increased significantly from 3.50 to 3.76
      g/dL (p < 0.05). There was no abnormality in any of the measured liver function
      tests. No patient developed an adverse or allergic reaction. We concluded that
      bolus intravenous infusion of iron dextran is an effective and well-tolerated
      method of repleting iron stores, and will allow a more efficient and economic use
      of rHuEPO in PD patients.

PMID- 8865895
TI  - Interpreting glycosylated hemoglobin in diabetic patients on peritoneal dialysis.
AB  - The limitations and usefulness of glycosylated hemoglobin (HbA1) as a means of
      assessing glycemic control in peritoneal dialysis (PD) and the importance of good
      glycemic control in diabetics on PD were analyzed. HbA1 levels may be elevated in
      renal failure because of either interference with the assay of HbA1 by
      carbamylated hemoglobin, which is formed by dissociation of urea to cyanate and
      condensation of cyanate with hemoglobin, or increased rate of formation of HbA1
      secondary to acidosis or other uremic effects. Interference with the assay of
      HbA1 is limited to methods separating HbA1 from hemoglobin A by electrical
      charges and is not encountered when chemical or immunologic assays are used. The
      proposed effect of uremia on the rate of formation of HbA1 was refuted by in
      vitro studies and in vivo multifactorial analysis, which showed that blood
      glucose level is the only important determinant of HbA1 in patients with renal
      failure. HbA1 levels may be low in uremia because of shortened red cell survival
      and/or frequent transfusions of red cells, conditions rarely encountered in PD
      patients. In the great majority of the reported studies, HbA1 regardless of the
      method of assay used, correlated with direct glycemic indices in patients with
      renal failure treated conservatively, by hemodialysis or by PD. Poor glycemic
      control, indicated by high HbA1 levels, is associated with adverse outcomes,
      including prolonged hospitalization and shortened survival, in diabetics on PD.
      HbA1 is a useful tool in assessing blood glucose control in PD. Good glycemic
      control is important for diabetics on PD.

PMID- 8865896
TI  - Transitioning adolescents from pediatric to adult dialysis units.
AB  - Transferring adolescent patients from pediatric to adult renal units can be
      difficult for all concerned. There has been little agreement or discussion on the
      factors involved in the timing of the transition. Communication and choice are
      key words when dealing with young people. The process of transition can be
      improved by discussion between the patient and team members on the likely timing
      of transition and the choice of an adult unit offering the same treatment
      modalities, for example, automated peritoneal dialysis. Information about the
      adult unit should be obtained, and liaison visits by patient, family members, and
      possibly accompanying staff are considered helpful. Transition should be a
      positive event, and each adolescent will require an individualized plan devised
      in discussion with team members.

PMID- 8865897
TI  - The effect of peritonitis on the peritoneal membrane transport properties in
      patients on CAPD.
AB  - Peritonitis is known to acutely affect the transport characteristics of the
      peritoneal membrane, however, the long-term effects are not known. We studied the
      effect of peritoneal inflammation on mean dialysate-to-plasma creatinine
      concentration ratio (D/P), dialysate protein losses (DPL, g/week), and dialysate
      albumin losses (DAL, g/week), done at six weeks or more postepisode, in 152
      patients [102 (67%) males, mean age 57 years (range 21-91)]. These patients were
      on continuous ambulatory peritoneal dialysis for a mean of twelve months (range 1
      97). A total of 94 distinct peritonitis episodes were managed in 47 patients
      (31%). The number of patients with 0, 1, 2, 3, 4, and 5 episodes of peritonitis
      were 105, 29, 3, 6, 4, and 5. These episodes were treated with a standard
      protocol. There were no statistically significant differences between the D/P,
      DPL, or DAL between the groups. The parameters did not show any correlation to
      time on dialysis. Thus, in conclusion, peritonitis, if promptly treated, does not
      cause any permanent change in D/P, DAL, or DPL.

PMID- 8865898
TI  - Treatment of CAPD-related peritonitis with ciprofloxacin: results after seven
      years.
AB  - We present the results of a protocol of empiric monotherapy of continuous
      ambulatory peritoneal dialysis (CAPD)-related peritonitis with ciprofloxacin
      (CPX), with a special emphasis on the evolution of our results after seven years
      of continued use of this drug. One hundred and fifteen episodes of bacterial
      peritonitis were treated with CPX between 1988 and 1992 (group A), and 115
      episodes were treated between 1993 and 1995 (group B). The etiologic spectrum of
      peritonitis was similar in both groups, except for a higher incidence of
      polymicrobial infections in group B. The clinical success rate decreased from
      86.5% in group A to 75% in group B (p < 0.05). This was partly due to the high
      failure rate of CPX against polymicrobial peritonitis, but the success rate also
      tended to decrease for gram-positive and, especially, gram-negative bacteria.
      However, in vitro sensitivity to CPX decreased only for coagulase-negative
      staphylococci, remaining stable for Staphylococcus aureus and gram-negative
      bacteria. CPX is still a valid alternative for the treatment of CAPD-related
      peritonitis in our unit. However, bacterial sensitivity must be closely
      monitored, especially in the case of coagulase-negative staphylococci. A
      different therapeutic approach may be indicated if polymicrobial peritonitis is
      suspected.

PMID- 8865899
TI  - Antifungal prophylaxis for secondary fungal peritonitis in peritoneal dialysis
      patients.
AB  - Our objective was to evaluate antifungal prophylaxis for secondary fungal
      peritonitis in peritoneal dialysis patients. The study was designed to
      investigate antifungal prophylaxis for fungal peritonitis and to compare the
      incidence of fungal peritonitis without (January, 1991-July, 1993) and with
      (August, 1993-December, 1995) antifungal prophylaxis. In a tertiary-referral
      university hospital, 122 end-stage renal disease (ESRD) patients (77 male, 45
      female) during period A (1/91-7/93) were observed for 1832 patient-months with no
      antifungal prophylaxis. One hundred and twelve ESRD patients (71 male, 41 female)
      during period B (8/93-12/95) were observed over 1705 patient-months with
      antifungal prophylaxis with fluconazole. Fluconazole 200 mg was given orally (po)
      as first dose at the onset of antibiotic therapy, then 100 mg po every other day,
      and was continued for one week after the antibiotic therapy. Forty-nine patients
      (28 male, 21 female; mean age 48.8 years) developed 105 episodes of peritonitis
      during period A. Forty-eight patients (36 male, 12 female; mean age 53.8 years)
      developed 95 episodes of peritonitis during period B. Fifteen episodes of fungal
      peritonitis occurred over 1832 patient-months during period A. while four
      episodes of fungal peritonitis were observed over 1705 patient-months during
      period B. Twelve episodes of secondary fungal peritonitis occurred during period
      A, while only two episodes occurred during period B. This incidence of secondary
      fungal peritonitis was significantly reduced with antifungal prophylaxis (p <
      0.02). No side effect of fluconazole was observed. In conclusion, secondary
      fungal peritonitis was significantly decreased following fluconazole antifungal
      prophylaxis at our center.

PMID- 8865900
TI  - Endogenous peritonitis and related outcome in peritoneal dialysis patients.
AB  - Our objective was to study endogenous peritonitis and related catheter outcome in
      peritoneal dialysis (PD) patients. The study was designed to investigate
      endogenous peritonitis and related catheter loss in all end-stage renal disease
      (ESRD) patients who started peritoneal dialysis from January, 1989 to September,
      1995. In a tertiary-referral university hospital, 192 ESRD patients (117 male, 75
      female) who entered the home program from 1/89 to 9/95 were studied. Sixteen
      episodes of endogenous peritonitis occurred in 15 PD patients (7 male, 8 female)
      with a mean age of 63 years (range 33-81 years). Five patients were diabetic. Two
      hundred and seventeen episodes of peritonitis in 192 patients occurred over 4149
      patient-months, resulting in one episode/19.1 patient-months. Sixteen episodes of
      endogenous peritonitis were encountered in 15 patients, accounting for 7% of all
      episodes of peritonitis. The mean duration of PD before contracting endogenous
      peritonitis was 24.2 months (range 7-52 months). Eleven episodes were related to
      diverticular leak/perforation, three to sigmoidoscopy/colonoscopy/PEG procedures,
      one to unknown etiology, and one to cholecystitis. During 11 episodes, severe
      constipation preceded. All the patients were initially treated conservatively
      with antibiotics. Five episodes (31%) responded to antibiotic therapy alongside
      antifungal prophylaxis and continued PD. One episode (6%) required
      cholecystectomy without catheter removal and resumed PD. Six episodes (38%)
      required catheter removal due to subsequent fungal peritonitis in a mean of 11
      days (range 3-24 days): 4 patients transferred to hemodialysis and 2 patients
      resumed PD. Three patients underwent catheter removal along with colectomy and
      colostomy: 2 patients transferred to hemodialysis and 1 patient died in ten days.
      One patient refused surgery and died in 16 days. Endogenous peritonitis resulted
      in a high incidence of catheter loss and dropout from PD. Peritonitis due to
      bowel leak without frank bowel perforation can be managed with antibiotic therapy
      and antifungal prophylaxis. Aggressive management of constipation may decrease
      endogenous peritonitis.

PMID- 8865901
TI  - Psychosocial factors and incidence of peritonitis.
AB  - It has been suggested that psychosocial (PS) factors may influence morbidity and
      mortality in chronically ill patients. However, investigators have not examined
      how PS factors affect specific medical problems in chronic peritoneal dialysis
      (CPD) patients. Sixty-eight patients maintained on CPD therapy were studied. PS
      testing included a self-rating form of patient-assessed quality of life (PaQOL),
      depression [Beck's Depression Inventory (BDI)], anxiety [Patient Rated Anxiety
      Scale (PRAS)], and assessment of physical symptoms (KDS-II). Peritonitis rates
      six months prior to PS assessment and six months after assessment were tabulated.
      The data show that during the study period patients with more than one episode of
      peritonitis compared to those with no episodes of peritonitis had: (1)
      significantly higher anxiety and physical symptom scores; (2) significantly lower
      PaQOL; and (3) higher depression scores, which did not reach statistical
      significance (p < 0.06). Whether higher peritonitis rates result in worse PS
      symptoms, or whether poor PS symptoms cause higher peritonitis rates needs to be
      determined with further investigations.

PMID- 8865902
TI  - Usefulness of the endotoxin test for assessing CAPD peritonitis by gram-negative
      organisms.
AB  - The endotoxin (ET) in cloudy peritoneal fluid was measured, and the usefulness of
      the method was examined. Thirteen continuous ambulatory peritoneal dialysis
      (CAPD) patients with an episode of peritonitis from December, 1993 to December,
      1995 were studied. The peritoneal fluid was collected without contamination from
      the bags and divided into two batches. The ET was measured in one of them with
      the limulus amebocyte lysate (LAL) assay, and the other was cultured for
      bacteria. Among the 13 patients ET was positive in 7 Gram-negative bacteria were
      identified in all 7 cases. Two of these patients were transferred to
      hemodialysis. On the other hand, gram-positive bacteria were cultured in only
      four episodes of the 6 ET-negative patients, all of which were treated
      successfully with vancomycin. Microbiological culture of the dialysate is still
      necessary for the treatment of peritonitis. But it takes 24-48 hours to obtain
      microbiological results. The result of the ET test can be given within one and
      one half hours (and it has 100% sensitivity and specificity for gram-negative
      peritonitis) at presentation in the episodes. Therefore, the ET test of the
      dialysate is very effective for the therapy of peritonitis in CAPD.

PMID- 8865903
TI  - Evaluation of healing and external tunnel histology of silver-coated peritoneal
      catheters in rats.
AB  - A previous study showed that silver-coating peritoneal catheters tended to
      decrease the incidence of early exit-site infections in rats. This study was
      designed to further evaluate the healing, biocompatability, and external tunnel
      morphology of standard and silver-coated catheters. Catheters were coated with
      silver by an ion beam-assisted process. Fourteen male Sprague-Dawley rats
      underwent implantation of either a standard or silver-coated double-cuff
      peritoneal catheter. Weekly observation and photographs documented exit-site
      characteristics. Erythema, exudate, loose fit, and poor hair growth were evidence
      of an inflamed exit. Overt infection was indicated by the presence of three or
      more of the following: erythema, purulent exudate, exuberant granulation tissue,
      loose fit, and poor hair growth. Animals were sacrificed at six weeks, and
      catheters were removed and processed for histology of the external tunnel.
      Multiple measurements were taken using a Filar eyepiece, and data were expressed
      as a mean of several readings. Inflammation, vascularity, and fibrosis were
      judged semiquantitatively. At the end of six weeks, six of the seven exits of the
      silver catheters showed excellent healing, while one exit site had signs of
      excessive inflammation. Four of the exit sites of the standard catheters healed
      well, two were inflamed, and one was overtly infected. The sinus tract of the
      standard and silver catheters had similar characteristics: keratinized and
      nonkeratinized epithelium lined the external part of the sinus tract and merged
      into granulation tissue. A fibrous sheath was noted in some sinus tracts between
      the granulation tissue and the cuff. The cuff evoked a foreign body reaction,
      with fibrosis, multiple giant cells, and vascularization. Poorly healing or
      infected sinus tracts had highly vascular granulation tissue with overlying
      exudate. The cuff of these catheters had marked inflammation and scanty giant
      cells, although collagen bundle thickness was similar to the well-healing
      catheters. In conclusion, silver-coating potentially enhances healing of the exit
      sites of peritoneal catheters. Additionally, the similarity of the tunnel
      histomorphology of standard and silver catheters confirms the favorable
      biocompatibility of silver.

PMID- 8865904
TI  - Surgical treatment of persistent exit-site infections.
AB  - Persistent exit-site infections and tunnel infections (ESI/TI) are a cause for
      removal of Swan neck catheters (SNC). Previous studies report variable success in
      the treatment of these infections by surgical exposure and removal of the
      subcutaneous external cuff. We report our experience with this technique. All 5
      patients with persistent ESI/TI were successfully treated with antibiotics and
      surgical intervention. All cultures grew Staphylococcus aureus. Average time to
      complete healing after surgical exposure was 39.4 days. Mean follow-up after
      complete healing was 164.8 days. There were no subsequent episodes of ESI/TI in
      these patients. None of the catheters subsequently malfunctioned or developed
      leaks. Persistent ESI/TI in Swan neck catheters can be successfully treated with
      surgical exposure and removal of the subcutaneous external cuff.

PMID- 8865905
TI  - Multiple use of disposable (tubing) set of HomeChoice automated peritoneal
      dialysis (APD) system in PD patients.
AB  - Our objective was to evaluate the multiple use of the tubing set of the
      HomeChoice automated peritoneal dialysis (PD) system in PD patients. The study
      was designed to reuse the tubing set of the HomeChoice automated PD system for
      two to seven treatments, each of 16-24 hours duration, in end-stage renal disease
      (ESRD) patients, and to continue to use the same set if the patient was
      disconnected for any reason. In a tertiary-referral university hospital, 17 ESRD
      patients on PD, admitted to a university hospital from January, 1995 to
      September, 1995, were studied. The patients were disconnected and connected in
      between or during PD treatments. Five-liter bags were used. All the fluid was
      either set initially or added as clinically indicated. One hundred and thirty
      eight PD treatments were performed with the HomeChoice automated PD system, using
      30 disposable (tubing) sets. Sixty-three disconnections were made for ambulation,
      transfer to other units, surgery, physical therapy, radiological investigations,
      and special procedures in between and during PD treatments. No episode of
      peritonitis occurred. The multiple use resulted in a 78% reduction in tubing sets
      and drain-line extension sets used, thereby reducing the disposable supplies and
      creating a substantial saving in nursing time. The multiple use of tubing sets of
      the HomeChoice automated PD system was safe and economical in patients undergoing
      automated PD in a hospital setting.

PMID- 8865906
TI  - Sealing the catheter exit site with dressing film and its effectiveness in
      preventing exit-site infection: bacterial culture.
AB  - In this study, we performed exit-site care using one of three methods (A: cleanse
      the exit site with povidone-iodine daily and apply gauze dressing; B: cleanse the
      exit site with povidone-iodine once a week, cover the site with a small gauze,
      and seal it completely with dressing film; C: the same as in B, above, except
      once every two weeks). The results show that there was a higher rate of positive
      bacterial growth in method A (17/24, 71%), and we concluded that the sterility of
      the exit site was not maintained 24 hours after cleansing. In methods B and C, in
      which the exit site was kept sealed, we did not detect bacterial growth in almost
      any of the cases (B = 0/44, C = 1/7). Although the patients took a bath and did
      not perform any care of the exit site for one to two weeks, the results show that
      the exit site was protected from bacterial invasion. We believe that this method
      could reduce exit-site infection while requiring no daily care.

PMID- 8865907
TI  - Does the response to hepatitis B vaccination predict CAPD-associated infections?
AB  - Rates of peritoneal dialysis-associated catheter infections and peritonitis were
      compared in continuous ambulatory peritoneal dialysis patients grouped on the
      basis of their response to hepatitis B vaccination with Engerix to assess the
      usefulness of vaccination in predicting patients at risk for peritonitis and
      catheter infections. Engerix was given intramuscularly in a dose of 40 micrograms
      at 0, 1, 2, and 6 months. Sixty-three percent (20/32) of patients developed
      hepatitis B surface antibodies (converters). Converters and nonconverters were
      not different in proportions of women, whites, diabetics, or Staphylococcus
      aureus nasal carriers; mean age and mean months on peritoneal dialysis were also
      not different. Overall, peritonitis (0.46/year vs 0.33/year) and catheter
      infection (0.53/year vs 0.54/year) rates were not different among converters and
      nonconverters, respectively. Nonconverters had higher S. aureus peritonitis rates
      (0.12/year vs 0.04/year, p < 0.05) but lower S. epidermidis peritonitis rates
      (0.03/year vs 0.18/year, p < 0.02). However, when the patient with recurrent S.
      epidermidis peritonitis was excluded from analysis, S. epidermidis peritonitis
      rates among converters and nonconverters were not different (0.13/year vs
      0.03/year, respectively, p < 0.09). These data suggest that the development of
      surface antibodies with hepatitis B vaccination does not predict a reduced risk
      of S. epidermidis peritonitis. The possibility that nonconverters are more likely
      to be S. aureus nasal carriers and therefore at greater risk of S. aureus
      peritonitis deserves further study.

PMID- 8865908
TI  - Use of laparoscopy in the management of malfunctioning peritoneal dialysis
      catheters.
AB  - The proper function of peritoneal dialysis (PD) catheters can be compromised by
      catheter malposition, fibrin clot, or omental wrapping. The purpose of this study
      was to determine the efficacy of laparoscopy in the treatment of malfunctioning
      PD catheters. All patients undergoing laparoscopy for catheter dysfunction at
      MetroHealth Medical Center in Cleveland, Ohio, from 1991 to 1995, were reviewed.
      Twenty-six laparoscopies were performed in 22 patients, for malfunction occurring
      an average of 3.9 months following insertion (range 0.5-18 months). Omental
      and/or small below wrapping as present in all but three cases. Lysis of adhesions
      was required in 19 of 26 cases, with repositioning only in seven. Eight patients
      had failed attempts at stiff wire manipulation prior to laparoscopy.
      Perioperative complications occurred in seven cases, consisting of temporary
      dialysate leakage (2), enterotomy (1), and early reocclusion (4). Repeat
      laparoscopy was successful in three of these four reocclusions. The overall
      success rate (catheter function > 30 days after laparoscopy) was 21/22 (96%).
      Laparoscopy is highly accurate and effective in the management of peritoneal
      dialysis catheter dysfunction and results in prolongation of catheter life.

PMID- 8865909
TI  - A simple method for opening an obstructed peritoneal catheter using an infusion
      accelerator.
AB  - Catheter obstruction by a fibrin clot is one of the early complications after
      catheter implantation in continuous ambulatory peritoneal dialysis (CAPD)
      patients. manual compression of the dialysis solution container is usually the
      initial method used in an attempt to dislodge clots formed in the catheter.
      However, it is usually difficult to achieve and maintain sufficient pressure to
      open the obstructed catheter by this method. Alternatively, forceful irrigation
      using a syringe with heparin or urokinase, or clot removal using a corkscrew clot
      remover can be tried. These conventional maneuvers may potentiate the chances for
      bacterial contamination. In addition, these procedures require hospital visits by
      the patient. To solve this problem, we developed a new infusion accelerator for
      CAPD. Recanalization was attempted using the infusion accelerator in six cases of
      complete catheter obstruction. The bag was pressurized to 450 mm Hg. In all six
      cases, catheter patency was completely recovered without any complications. After
      appropriate training of patients, this method may be performed by patients
      themselves. Given the ease and efficiency of this procedure utilizing the
      improved equipment, we think that in cases with complete catheter obstruction
      this method should be considered before initiating more invasive procedures.

PMID- 8865910
TI  - Peritoneal catheter-related complications: a comparison between hemodialysis and
      intermittent peritoneal dialysis in the break-in period.
AB  - We prospectively monitored the clinical outcome of 89 curled, double-cuff
      peritoneal catheters (PC) implanted by surgeons over one year. Thirty-six cases
      (40%) were supported with hemodialysis (HD) (group A) and 53 cases (60%) were
      supported with weekly intermittent peritoneal dialysis (IPD) (small exchange
      volume with a cycler) (group B) for four weeks before commencing continuous
      ambulatory peritoneal dialysis (CAPD). PC-related complications between the two
      groups were compared. Ten cases failed to complete the six-month observation
      period (8 died, 1 received kidney transplant, and 1 defaulted follow-up),Total
      experience accumulated was 494 patient-months (195 patient-months in group A, 299
      patient-months in group B). The incidence of pericatheter leakage (group A vs
      group B) was significantly higher in group B (0% vs 13%, p < 0.05). There were no
      significant differences in the incidence of other PC-related complications,
      removal of PC, and mortality rate in the two groups. The incidence of
      pericatheter leakage was significantly higher in diabetic patients (71% vs 22%, p
      < 0.05), and group B patients with leakage had a higher incidence of external
      cuff erosion 57% vs 7%, p < 0.005) and delay in CAPD training (71% vs 7%, p <
      0.005). We conclude that both HD and IPD are equally safe renal replacement
      therapies in the break-in period, while patients supported with IPD had a higher
      incidence of pericatheter leakage, which was associated with other catheter
      related morbidities including external cuff erosion and delay in CAPD training.

PMID- 8865911
TI  - Home ascites drainage using a permanent Tenckhoff catheter.
AB  - Management of refractory ascites (RA) can be accomplished in many ways. Rapid
      recurrence will be a problem even with repeated paracentesis. We studied the use
      of a permanent Tenckhoff catheter (PTC) for drainage of RA in 10 patients. The
      cause of RA was cardiomyopathy in 7 patients, malignancy with liver metastasis in
      2, and end-stage liver disease in 1 patient. The volume of ascites drained (AD)
      ranged from 0.5-7.0 L, with a mean of 2.6 L. Mean blood pressure pre-AD was
      112/68 mm Hg, and post-AD was 109/66 mm Hg (p > 0.05). Heart rate pre- and post
      AD was 80 bpm and 81 bpm, respectively (p > 0.05). The number of ADs ranged from
      two to 63 (mean: 16). There was no fluid replacement during or post-AD. There
      were no complications or infections from AD. The mean interval between ADs was
      7.8 days. Mean duration of survival was six months. All patients eventually
      expired. In conclusion, PTC can be a useful and safe alternative for draining RA
      at home in terminally ill patients. Complications of repeated paracentesis are
      minimized, and the need for hospitalization is avoided. AD with PTC may be
      preferred to repeated paracentesis in RA.

PMID- 8865912
TI  - Effect of CAPD and hemodialysis on parathyroid function.
AB  - A high incidence of low turnover bone disease (LTBD) has been reported in
      predialysis and dialysis uremic patients, despite parathyroid hormone (PTH)
      levels two- to four-fold the upper normal limit. The aim of this study was to
      evaluate the trend of PTH in uremic patients after admission to continuous
      ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD). Thus, we evaluated 53
      patients (27 CAPD and 26 HD) of 73 consecutive uremic patients starting CAPD or
      HD from 1992, who had at least one year follow-up on dialysis. HD and CAPD
      patients were comparable for age, nephropathy, and duration of uremia. All the
      patients had been treated with calcium carbonate (CaCO3) as the sole phosphate
      binder during the predialysis period. At the time of admission to dialysis PTH
      was > 260 pg/mL (fourfold above the upper normal limit) in 12 CAPD and 9 HD
      patients, between 130 and 260 pg/mL in 6 CAPD and 5 HD patients, and < 130 pg/mL
      in 9 CAPD and 12 HD patients. Bone biopsy, performed in 22 patients, showed LTBD
      in 10 of 12 patients with PTH < 130 pg/mL and high bone turnover in 8 patients
      with PTH > 260 pg/mL. Patients were treated with a dialysate calcium (Ca) of 1.75
      mmol/L and were given CaCO3 to maintain serum phosphate < 5 mg/dL. Oral
      calcitriol was given if they developed hypocalcemia (< 9 mg/dL). Hypercalcemia (>
      10.5 mg/dL) occurred in 13 CAPD and 17 HD patients, and was managed by
      discontinuation of calcitriol and reduction of dialysate Ca to 1.25-1.5 mmol/L. A
      significant decrease in PTH and alkaline phosphatase was observed in both groups
      after six and 12 months of treatment. After one year of CAPD, PTH was > 260 pg/mL
      in 3 patients, between 130 and 260 pg/mL in 4 (all on calcitriol), and < 130
      pg/mL in 20 patients (17 on calcitriol, but only 2 mild hypercalcemic). After one
      year of HD, PTH was > 260 pg/mL in 3 patients, 130-260 pg/mL in 5 (all on
      calcitriol), and < 130 pg/mL in 18 (11 on calcitriol, 1 mild hypercalcemic). IN
      CONCLUSION: (1) about 40% of predialysis patients treated with CaCO3 showed PTH
      levels suggestive of LTBD; (2) the proportion of patients with low PTH increases
      after one year on CAPD or HD, even though calcemia was maintained within the
      normal range; (3) suppressed PTH levels are associated with calcitriol therapy
      rather than dialysis modality; and (4) secondary hyperparathyroidism improves in
      most patients after one year on CAPD or HD.

PMID- 8865913
TI  - Evaluation of bone mineral density in CAPD patients with dual energy X-ray
      absorptiometry.
AB  - In this study bone mineralization was evaluated using dual energy x-ray
      absorptiometry (DEXA), which measured regional bone mineral density [BMD (g/cm2)]
      at two skeletal sites, the lumbar spine and the femur, in 33 patients (15 male,
      18 female) undergoing continuous ambulatory peritoneal dialysis (CAPD) with no
      history of chronic disease or medications affecting bone. The biochemical profile
      included measurements of plasma levels of calcium, phosphorus, alkaline
      phosphatase, and intact parathyroid hormone (iPTH). We did not find any
      statistically significant difference or correlation between BMD and the examined
      parameters, except for the lower BMD values in the female population. Because of
      the reported findings of significantly lower PTH levels in CAPD patients with low
      turnover bone disease (adynamic bone disease) and the higher prevalence in CAPD
      than in hemodialysis patients, we tried to evaluate any correlation between BMD
      and iPTH levels in CAPD patients that were separated into two groups: group A
      (iPTH < 200 pg/mL), 13 patients, and group B (iPTH > 200 pg/mL), 20 patients.
      Data analysis revealed a negative correlation between PTH levels and BMD values
      (r = -0.66, p = 0.014) as PTH and serum calcium (r = -0.77, p = 0.002) only in
      group A. No other statistically significant changes were observed. These findings
      suggest that there is a favorable influence of CAPD modality on bone
      mineralization, while no special DEXA findings are representative of the possible
      appearance of adynamic bone disease.

PMID- 8865914
TI  - Low calcium (1.25 mmol/L) dialysate can normalize relative hypoparathyroidism in
      CAPD patients with low bone turnover.
AB  - Recently, several reports have suggested that there is a higher incidence of low
      turnover bone in the absence of aluminium exposure in peritoneal dialysis
      patients than in hemodialysis patients. Relative hypoparathyroidism with mild
      hypercalcemia, induced by a positive calcium balance, is considered to be one of
      the major causes of this disorder. Thus, we recruited 9 continuous ambulatory
      peritoneal dialysis (CAPD) patients with relative hypoparathyroidism and low bone
      turnover [intact parathyroid hormone (iPTH) < 50 pg/mL, intact osteocalcin < 10.0
      ng/mL] who had been prescribed 1.75 mmol/L calcium (Ca) dialysate for 5.0 +/- 0.3
      years. They were then treated by low Ca (1.25 mmol/L) dialysate for nine months
      without vitamin D and aluminum administration. Intact PTH and bone metabolic
      markers [intact osteocalcin, alkaline phosphatase (ALP)] were measured every
      three months. Intact PTH levels increased from 21.1 +/- 3.8 to 159.2 +/- 32.8
      pg/mL after the first three months; thereafter, those levels were maintained at
      around 150 pg/mL. On the other hand, intact osteocalcin levels rose consecutively
      from 6.7 +/- 1.2 to reach 22.0 +/- 3.8 ng/mL after nine months. Interestingly,
      the pattern of time course changes between PTH and intact osteocalcin was
      different. ALP activity did not change during the nine-month period. Corrected
      serum calcium was significantly decreased (p < 0.001) to approximately 0.25
      mmol/L within one month, and the level remained almost the same thereafter. The
      serum phosphate level did not change without adjusting the original dose of
      calcium carbonate as a phosphate binder. We concluded that low Ca dialysate (1.25
      mmol/L) is effective for the treatment of CAPD-related hypoparathyroidism with
      low bone turnover.

PMID- 8865915
TI  - Calcium lactate interference in measuring creatinine in peritoneal dialysis
      fluids by the Jaffe kinetic method.
AB  - Creatinine measurements in peritoneal dialysis fluids using the Jaffe method have
      poor specificity due to interfering substances. We have checked to see if calcium
      lactate, in addition to glucose, interferes with the Jaffe kinetic measurement.
      Eight samples were prepared with increasing concentrations of glucose (960-3890
      mg/dL) and eight were prepared with the same glucose content plus 7 mg/dL of
      calcium lactate, all without creatinine; in addition, 96 samples with increasing
      concentrations of glucose (1500-4000 mg/dL), calcium lactate (3-7.5 mg/dL), and
      creatinine (0.75-4.5 mg/dL) were prepared. There was a 0.31 +/- 0.13 mg/dL
      glucose interference on the Jaffe kinetic measurement in the first series, with
      an exponential trend. Interference was greater with calcium lactate and glucose:
      0.50 +/- 0.16 mg/dL with the same trend. Data from the second series confirm the
      overestimation: 0.54 +/- 0.05 mg/dL (32.6%) with an exponential trend. The
      interference of glucose, creatinine, and calcium lactate on the Jaffe kinetic
      measurement was obtained by multi-variate regression. The single effects of
      glucose2 and glucose are predominant, but both creatinine and calcium lactate
      have a significant effect. Our study highlights the nonlinear glucose
      interference on creatinine measurement with the Jaffe kinetic method and the
      linear interference of both calcium lactate and creatinine.

PMID- 8865916
TI  - Lipid-lowering effects of simvastatin and gemfibrozil in CAPD patients: a
      prospective cross-over study.
AB  - We compared the lipid-lowering effects of simvastatin, a 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitor, and gemfibrozil, a fibric acid
      derivative, in 22 continuous ambulatory peritoneal dialysis patients whose serum
      total cholesterol and/or triglyceride levels were > or = 220 mg/dL after a
      standard diet for six months. The study group was first treated with gemfibrozil
      (600 mg/b.i.d.) for three months (stage 1). After a wash-out period of two
      months, during which no treatment was given, all of the patients became
      hyperlipidemic again and, therefore, were given simvastatin (10 mg/day) for three
      months (stage 2), which was followed by another two-month wash-out period. A
      control group, which served to evaluate the natural progression of
      pharmacologically untreated dyslipidemia, was followed during the same period.
      Blood determinations of triglyceride, total cholesterol, and high-density
      lipoprotein (HDL) cholesterol were performed after each step. Low-density
      lipoprotein (LDL) cholesterol and HDL ratio were calculated from the measured
      values. Both gemfibrozil and simvastatin improved all parameters of the lipid
      profile, but the effect of simvastatin was better than that of gemfibrozil (-69
      vs -39 mg/dL for triglyceride and -95 vs -64 mg/dL for cholesterol), while their
      actions on LDL and HDL cholesterol were of equal magnitude. Two months after
      discontinuation of simvastatin, significant decreases of total cholesterol (-46
      mg/dL) and triglyceride (-60 mg/dL) were still present, while these values had
      returned to pretreatment levels after stopping gemfibrozil. The HDL ratio
      remained markedlyhigher (p < 0.05) during the wash-out period after simvastatin,
      while it decreased to pretreatment values after gemfibrozil was stopped. The
      lipid profile of the control group did not change during the follow-up. Both
      drugs were well tolerated, and no serious side effects occurred.

PMID- 8865917
TI  - Is an elevated level of serum lipoprotein (a) a risk factor for cardiovascular
      disease in CAPD patients?
AB  - Cardiovascular disease (CVD) is the single most important cause of mortality in
      hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients.
      An increased lipoprotein (a) [Lp(a)] level in HD patients is associated with CVD.
      However, Lp(a) levels in CAPD patients are controversial, and their association
      with CVD has not been established. In the present study, prevalent CAPD and HD
      patients [excluding those who were human immunodeficiency virus (HIV)-positive]
      attending the Long Island College Hospital from June, 1990 to July, 1995
      underwent analysis of lipid profile including Lp(a). Total and low-density
      lipoprotein cholesterol, triglycerides, apolipoprotein (apo) A, and apo B were
      all significantly increased in CAPD patients compared to HD patients. Serum Lp(a)
      levels were also significantly higher in CAPD patients than in HD patients (51 +/
      32 vs 34 +/- 23 mg/dL, p < 0.001). CAPD patients who had a history of myocardial
      infarction (MI) or coronary artery disease (CAD) at enrollment had significantly
      higher Lp(a) levels compared to those who did not have a history of MI or CAD.
      CAPD patients who died of CVD had higher Lp(a) levels than patients who died of
      non-CVD causes. In the Cox model with backward stepwise selection, a history of
      CVD was associated with a significantly elevated relative risk (RR) of mortality
      (RR = 1.84, p = 0.014). Expected survival by all causes of mortality and by
      cardiac mortality was significantly shorter in patients with a history of CVD
      than in those without a history of CVD. Thus, elevated Lp(a) is related to
      increased CVD and therefore may contribute to increased mortality in CAPD
      patients.

PMID- 8865918
TI  - Recommendations for dietary protein intake in CAPD patients.
AB  - Protein malnutrition occurs in 41%-42% of peritoneal dialysis (PD) patients,
      indicating that the current intake of protein is inadequate in many patients.
      With an intake of protein > or = 1 g/kg/day, most continuous ambulatory
      peritoneal dialysis (CAPD) patients are in positive or neutral nitrogen balance,
      while with an intake below this there is considerable risk of negative nitrogen
      balance. Most CAPD patients are prescribed a diet containing 1.2 g/kg/ day
      protein or higher, yet the majority of patients have an intake lower than this.
      Several factors are associated with inadequate protein intake including older
      age, comorbidity, and loss of residual renal function when the dialysis regimen
      is inadequate. A minimum weekly Kt/V of 2.0 is needed to achieve a protein intake
      of 0.9-1.0 g/kg/day. Patients with peritonitis and a permeable membrane have
      increased losses of protein via the dialysate, and so are at risk for protein
      malnutrition. To prevent and treat protein malnutrition, routine assessment of
      both nutritional status and dialysis adequacy are needed. Patients with an
      adequate clearance (weekly Kt/V of 2.0 or higher, creatinine clearance of 60
      L/week/1.73 m2), who are eating 1 g/kg/day and have no markers of malnutrition,
      including a normal serum albumin, require no intervention. Protein supplements
      can be prescribed to increase the protein ingestion to 1.2 g/kg/day or more, if
      the serum albumin is low, or if the patient is clinically malnourished with
      weight loss and decreased muscle mass. Gastro-paresis and esophagitis, common in
      PD patients, can be treated. If supplements, dietary counseling, and adequate
      dialysis regimen do not result in improvement of nutritional status, amino acid
      dialysate may be beneficial. One to two exchanges per day using amino acid
      dialysate converts the nitrogen balance from neutral to positive in malnourished
      CAPD patients. To use amino acid dialysate successfully, the physician must be
      sure that the clearance is adequate as the serum urea nitrogen rises; inadequate
      dialysis can result in uremia and decreased intake.

PMID- 8865919
TI  - Nutritional parameters in diabetic patients on CAPD.
AB  - In diabetic patients treated with dialysis, morbidity and mortality are more
      elevated than in nondiabetic patients. For the high dropout of diabetic patients
      between the first and the second year of treatment not much data are available on
      their nutritional parameters. For this reason, after excluding patients who had
      not had a two-years follow-up, we compared two groups of patients, 8 diabetics
      and 10 nondiabetics, similar in age (66.0 +/- 8.1 vs 65.0 +/- 8.3 years) and
      weight (61.8 +/- 11.9 vs 62.1 +/- 5.5 kg), measuring their nutritional parameters
      [body mass index (BMI), normalized protein catabolic rate (PCRN), albumin,
      transferrin, cholesterol], dialytic dose (Kt/V), renal residual function (RRF)
      and peritoneal urea (Kdu) and creatinine clearances (Kdcr) after one and 24
      months of continuous ambulatory peritoneal dialysis (CAPD). At the start of CAPD,
      diabetics had greater weekly Kt/V (2.77 +/- 0.68 vs 2.19 +/- 0.35, p < 0.03) for
      a better residual renal function (5.0 +/- 2.0 vs 2.6 +/- 1.6 mL/min, p < 0.01)
      and greater loss of proteins in dialysate (7.8 +/- 2.3 vs 5.2 +/- 2.1 g/day, p <
      0.05). After 24 months diabetic patients showed a significant decrease in albumin
      (3.44 +/- 0.34 vs 2.92 +/- 0.33 g/dL, p > 0.01), PCRN (1.21 +/- 0.20 vs 0.92 +/-
      0.10 g/kg/day, p < 0.02), and weekly Kt/V (2.77 +/- 0.68 vs 2.25 +/- 0.38, p <
      0.05), and a reduction, even if not as significant as with nondiabetic patients,
      in residual renal function (5.0 +/- 2.0 vs 3.0 +/- 2.3, p = NS). BMI (p < 0.01)
      was significantly increased in both groups, and this increase is higher in
      diabetic patients, while transferrin and cholesterol had no significant
      variations in both groups of patients. Peritoneal clearances did not change in 24
      months, whereas the daily protein loss into dialysate was constantly higher in
      diabetic patients. In conclusion, diabetic patients have, over time, a decrease
      of total (renal and peritoneal) clearances of urea and creatinine (primarily
      because of loss of residual renal function, a reduced protein intake (evaluated
      as PCRN), and an increased loss of proteins from the peritoneum, which bring
      about a decrease in albuminemia, a possible concomitant cause of the greater
      morbidity and mortality in diabetic patients.

PMID- 8865920
TI  - Protein catabolic rate in CAPD patients: comparison of different techniques.
AB  - Protein intakes of patients on continuous ambulatory peritoneal dialysis (CAPD)
      are estimated by protein catabolic rate (PCR) or dietary protein intake
      assessments (DPI). In this study we compared two approaches suggested by
      Randerson et al. for calculating PCR. One method incorporates urea generation
      rate (UG) and estimated dialysate protein losses (PCR), while the other includes
      UG and measured dialysate protein losses (PCR). We feel that calculating PCR2 is
      more convenient in practice. We studied 95 patients on CAPD, 49 men and 46 women,
      with a mean age of 56.5 years (range 26.6-84.5 years) and lean body mass of 41 kg
      (range 19-71 kg). Mean +/- SEM of PCR1, PCR2, and DPI were: 0.89 +/- 0.02, 0.86
      +/- 0.02, and 0.90 +/- 0.04 g/kg standard weight (std wt)/day, respectively. PCR1
      and PCR2 were highly and significantly correlated (r = 0.94, p = 0.0001). The
      difference of PCR1-PCR2 is plotted against dialysate protein loss, which reveals
      that PCR2 often underestimates PCR1 if dialysate protein loss is > 10 g/day, but
      this difference is minimum (< 0.1 g/kg standard weight/day) when the dialysate
      protein loss is < 15 g/day. We conclude that PCR2 is an easy and effective method
      to monitor nutritional status in the majority of CAPD patients as very few will
      have dialysate protein losses > 15 g/day.

PMID- 8865921
TI  - Factors affecting low values of serum albumin in CAPD patients.
AB  - To investigate the factors affecting low values of serum albumin (SA) in
      continuous ambulatory peritoneal dialysis (CAPD) patients, we undertook a cross
      sectional study of 106 CAPD patients, with a mean age of 49.0 years and dialysis
      duration of 43.4 months, with respect to demographic, clinical, and biochemical
      parameters. In group I (n = 28, SA < or = 3.5 g/dL), diabetics were more common,
      patients were significantly older, and more patients were malnourished, according
      to the subjective global assessment (SGA), compared to group II (n = 78, SA > 3.5
      g/dL). Serum C-reactive protein (CRP), lipoprotein (a), and 24-hour dialysate-to
      plasma creatinine concentration ratio (D/P) were significantly higher, and 24
      hour dialysate albumin was greater in group I. Compared to group II, group I had
      significantly lower serum creatinine and urea nitrogen appearance (UNA). Blood
      urea nitrogen (BUN), lean body mass (LBM), % of body weight (%BW), and normalized
      protein equivalent of nitrogen appearance (nPNA) tended to be lower in the low SA
      group, without statistical significance. There were no differences in the
      duration of CAPD, peritonitis rate, serum insulin-like growth factor-I (IGF-I),
      anthropometric data, dietary assessment, dialysis adequacy, and residual renal
      function (RRF) between the two groups. SA was positively correlated with serum
      creatinine, IGF-I, LBM, UNA, BUN, nPNA, and CAPD duration, and was negatively
      correlated with 24-hour D/P, 24-hour dialysate albumin, age, CRP, and bicarbonate
      (HCO3-). By stepwise multiple logistic regression analysis, 24-hour D/P, age,
      CRP, and SGA were independent risk factors for low SA level. In conclusion, SA
      seems to be influenced not only by nutritional factors but also by nonnutritional
      factors such as peritoneal membrane transport characteristics, age, and presence
      of acute phase protein response manifested by CRP elevation.

PMID- 8865922
TI  - Nutrition of uremic patients in the course of CAPD treatment.
AB  - Our aim was an evaluation of daily protein and energy intake, plasma protein,
      albumin, and cholesterol concentrations as well as total iron binding capacity in
      the course of continuous ambulatory peritoneal dialysis (CAPD) for up to 36
      months. Our results indicate that CAPD patients, despite adequate clinical
      laboratory scores for up to 36 months of treatment, usually do not show optimal
      protein intake. When protein calorie malnutrition is prolonged, plasma proteins
      decrease. On the other hand, the greater the peritoneal permeability the lower
      the plasma protein intake.

PMID- 8865923
TI  - Impact of peritoneal dialysis modality on nutritional and biochemical parameters.
AB  - Several lines of evidence suggest that continuous ambulatory peritoneal dialysis
      (CAPD) and continuous cycling peritoneal dialysis (CCPD) may differ in glucose,
      amino acid, and protein mass transfer. Thus, depending on modality, variances in
      protein and caloric balance could affect nutritional parameters. We prospectively
      followed 58 patients on CAPD (n = 36) or CCPD (n = 22) for 21 months (age: 54 +/-
      14 years; weight: 76 +/- 16 kg; body mass index: 25.8 +/- 5.1 kg/m2). Twenty-four
      hour dialysate effluent (Kpt/V) and normalized protein catabolic rate values were
      comparable in both CAPD and CCPD patients (0.23 +/- 0.05 vs 0.20 +/- 0.05 and
      0.93 +/- 0.23 vs 0.87 +/- 0.21 g/kg/day, respectively). At the last trimester,
      CAPD patients had greater body weight and body mass index increases than those on
      CCPD (1.6 +/- 1.1 vs 0.3 +/- 1.1 kg and 0.53 +/- 0.42 vs 0.06 +/- 0.35 kg/m2,
      respectively), which did not reach statistical significance. No differences were
      noted in serum protein, albumin, or cholesterol levels (6.5 +/- 0.1 vs 6.5 +/-
      0.2 g/dL; 3.5 +/- 0.1 vs 3.7 +/- 0.1 g/dL; and 211 +/- 10 vs 209 +/- 10 mg/dL for
      CAPD and CCPD, respectively). In summary, this study demonstrates that CAPD and
      CCPD, when delivered in equal amounts, result in similar weight gains and
      maintain comparable biochemical nutritional parameters.

PMID- 8865924
TI  - Prevalence of malnutrition in Mexican CAPD diabetic and nondiabetic patients.
AB  - Malnutrition is often present on continuous ambulatory peritoneal dialysis
      (CAPD), and contributes to morbidity and mortality. Diabetics (DM) have an
      increased risk for developing malnutrition. Our purpose was to assess the
      nutritional status (NS) of our CAPD population, to define NS differences between
      DM and nondiabetics (NoDM), and to identify NS-related factors. Patients were
      subjected to a nutritional assessment, which included a 24-hour dietary recall
      and a nutritional scoring system including anthropometric, biochemical, and
      subjective evaluation, and that classifies patients as: normal, and mildly,
      moderately, and severely malnourished. We studied 90 patients: 35 DM and 55 NoDM.
      In our whole population we observed a high frequency of malnutrition: NS was
      normal in 18%, and 20% had mild, 24% had moderate, and 38% had severe
      malnutrition. Ninety-one percent of DM and 76% of NoDM showed some degree of
      malnutrition. DM patients had significantly higher levels of malnutrition (p =
      0.02), were significantly older, had more body fat, and spent less time on
      dialysis. There were 37 males and 53 females. Sex distribution was similar
      between DM and NoDM. Seventy-six percent of males and 86% of females had
      malnutrition. Moderate and severe malnourishment were more frequent in females.
      DM and female sex were the strongest predictors for moderate and severe
      malnutrition.

PMID- 8865925
TI  - Impact of acidosis on nutritional status in chronic peritoneal dialysis patients.
AB  - Malnutrition is a well-recognized risk factor for survival in chronic dialysis
      patients. Experimental evidence links acidosis to decreases in albumin synthesis
      and increased breakdown. We studied serum bicarbonate, albumin, and total protein
      concentrations in 79 peritoneal dialysis patients (mean age 53 +/- 14 years)
      during a 21-month observation period. No changes were observed in blood urea
      nitrogen (66 +/- 19 vs 61 +/- 18 mg/dL), serum creatinine (9.8 +/- 4.5 vs 10.7 +/
      4.5 mg/dL), serum bicarbonate (25 +/- 3 vs 25 +/- 3 mEq/L), anion gap (16 +/- 3
      vs 17 +/- 3 mEq/L), and serum albumin (3.6 +/- 0.6 vs 3.6 +/- 0.6 g/dL)
      concentrations between the first and last trimester of follow-up. A poor
      correlation was also found between serum albumin concentration and anion gap (R =
      -0.373) and bicarbonate (R = -0.172) concentrations. Finally, when grouped by
      acid-base status, serum protein (6.5 +/- 0.7 vs 6.5 +/- 0.8 g/dL) and albumin
      (4.0 +/- 0.4 vs 3.9 +/- 0.4 g/dL), concentrations were similar in patients with
      serum bicarbonate levels < or > or = 22 mEq/L, respectively. In conclusion, a
      mild to moderate degree of acidosis is not associated with decreases in serum
      albumin concentrations in stable chronic peritoneal dialysis patients.

PMID- 8865926
TI  - Nutritional effects of amino acid dialysate (Nutrineal) in CAPD patients.
AB  - The use of amino acid dialysate (AAD) has been shown to improve the nutritional
      status of malnourished continuous ambulatory peritoneal dialysis (CAPD) patients.
      We report on a randomized, prospective, cross-over study evaluating the effects
      of a single, daily, postprandial 2-L exchange of 1.1% AAD (Nutrineal) on a
      nutritionally unselected group of 18 stable CAPD patients. Patients in group A (n
      = 10) were randomized to receive AAD in the initial six months, whereas group B
      (n = 8) patients received AAD in the final six months of the study. Regular
      biochemical, hematological, and anthropometric measurements were made. A
      computerized nutrition score(1) combined anthropometry, serum albumin, and total
      lymphocyte count. Improved nutritional status was indicated by a decreased score.
      Mean serum albumin and transferrin did not show a significant rise in either
      group. However, patients in group A, with a mean serum albumin of less than 30
      g/L, showed a significant rise at two months, which persisted at six months (26.8
      g/L on entry, 29.0 g/L at two months, 30.1 g/L at six months; p < 0.05 and p <
      0.01, respectively). Treatment with AAD showed a trend towards improvement in
      midarm muscle circumference in both groups (22.9 -23.5 cm, group A; 22.9-23.7 cm,
      group B). The nutrition score improved in both groups but was significant only in
      group A (14.6 to 13.1; p = 0.02). These effects of AAD on the nutritional status
      of CAPD patients need validation in a long-term study to evaluate the effects on
      morbidity and mortality.

PMID- 8865927
TI  - The influence of nutritional status, dialysis adequacy, and residual renal
      function on the response to hepatitis B vaccination in peritoneal dialysis
      patients.
AB  - Little is known about the factors contributing to the reduced antibody response
      to hepatitis B vaccination in peritoneal dialysis patients. The influence of
      nutritional status [as assessed by serum albumin and nitrogen protein appearance
      (nPNA)], residual renal function, and dialysis adequacy (weekly Kt/V(urea)) on
      the development of hepatitis B antibodies was examined in 32 continuous
      ambulatory peritoneal dialysis/continuous cycling peritoneal dialysis patients.
      Vaccination with Engerix 40 micrograms given intramuscularly at 0, 1, 2, and 6
      months resulted in a 63% response with 20 converters and 12 nonconverters.
      Patient age, sex, months on peritoneal dialysis, and race were not different
      among converters and nonconverters. Median serum albumin (3.75 vs 3.8 g/dL), nPNA
      (0.96 vs 0.94 g/kg/day initial and 0.78 vs 0.84 g/kg/day final), residual renal
      function (5.4 vs 4.0 mL/min), and final weekly Kt/V (2.12 vs 1.96) were not
      different among converters and nonconverters, respectively. Initial Kt/V was
      higher in converters (2.37 vs 2.01, p = 0.02). Nutritional status, residual renal
      function, and weekly Kt/V in nutritionally replete and well-dialyzed peritoneal
      dialysis patients do not predict response to hepatitis B vaccine. Patients with
      higher weekly Kt/V early in the course of peritoneal dialysis may be more likely
      to respond to hepatitis B vaccination.

PMID- 8865928
TI  - Outgrowth of interleukin-2-dependent T cell lines with cytotoxic activity against
      mesothelial cells from cultures of peritoneal effluent cells of children on CPD.
AB  - Previous studies on the peritoneal immune system described the presence of
      activated T lymphocytes in peritoneal effluents (PE) from patients on chronic
      peritoneal dialysis (CPD), and showed that mesothelial cells (MC) can present
      antigens to T cells. In order to better define phenotypic and functional
      characteristics of T cells and their interactions with MC, we isolated PE cells
      from 15 children. At the immunophenotypic analysis, high percentages of activated
      T cells were identified (mean value: 15% double staining for CD3/DR; 12% CD25+).
      T cells with gamma/delta T cell receptor (mean 5%) and natural killer cells (mean
      17%) were also present in elevated numbers. MC lines (n = 7) and interleukin-2
      dependent T cell lines (9 CD4+; 1 CD8+) were also obtained by incubating PE cells
      under different conditions. Two cell lines showed a major histocompatibility
      complex (MHC) restricted cytotoxic activity against autologous MC; two lines
      killed allogeneic MC; one line killed both autologous and allogeneic MC. Although
      the hypothesis that activated T cells could kill MC after recognition of surface
      structures modified by dialysis fluid, or during antigen presentation, needs to
      be further investigated, our data suggest that the subsets of lymphocytes we
      identified could play an important role in the mechanisms of peritoneal membrane
      defense.

PMID- 8865929
TI  - Protein and calorie intake, nitrogen losses, and nitrogen balance in children
      undergoing chronic peritoneal dialysis.
AB  - We performed 22 nitrogen balance (NB) studies of three days' duration in 19
      children (8.7 +/- 3.8 years) on chronic peritoneal dialysis (CPD) for 19.4 +/-
      16.4 months. The dietary intakes were assessed by the double weighing method.
      Total nitrogen, protein, urea, and creatinine were analyzed in the dialysate and
      urine collected daily. Total nitrogen was also determined in the feces collected
      over the whole NB study period, using vegetable charcoal as a marker. The protein
      intake was 1.64 +/- 0.50 g/kg/day, corresponding to 126 +/- 40% of the
      recommended daily allowance (RDA) for normal children of the same age, and the
      calorie intake (diet+glucose from dialysate) reached 75 +/- 26% of RDA. Nitrogen
      losses were: 0.177 +/- 0.052 g/kg/day with peritoneal fluid and urine, and 0.028
      +/- 0.018 g/kg/day with feces. The NB, positive in 17 out of 22 studies, ranged
      from -116 to +167 mg/kg/day (mean 44.0 +/- 66.2 mg/kg/day). A direct and
      significant correlation between NB and nitrogen intake (g/kg/day) (r = 0.562, p <
      0.05) and total calorie intake (cal/kg/day) (r = 0.483, p < 0.05) has been
      observed. These data confirm the need to ensure in children on CPD an adequate
      nutritional intake, and further support the efforts to improve calorie intake.

PMID- 8865930
TI  - Relationship between intraperitoneal hydrostatic pressure and dialysate volume in
      children on PD.
AB  - As a result of the theoretical risk of an excessive increase in intraperitoneal
      pressure (IPP) in association with peritoneal dialysis, reduction of instilled
      intraperitoneal dialysate volume (IPV) is often proposed in infants compared to
      adults; a further reduction is often noted in neonates compared to children. To
      better evaluate the significance of this risk, we have tested the relationship
      between the IPP (cm of water) and the IPV (mL/m2) in our population of children
      on peritoneal dialysis (n = 17) during the last three years. IPP was measured
      after a nocturnal dialysis session, during a morning study day, after sequential
      exchanges of ten minutes' dwell time each, with progressively increased instilled
      dialysate volumes from 600 to 1400 mL/m2. Mean IPP values were 8.2 +/- 3.8 cm for
      a mean IPV of 990 +/- 160 mL/m2 body surface area. These values are lower than
      the IPP values established for adults (13.4 +/- 3.1 cm), which were given for
      higher IPV values of 1585 +/- 235 mL/m2. The relationship between IPP and IPV was
      age-dependent. In neonates, stable IPP values (3.5 +/- 1.6 cm) were noted for IPV
      from 600 to 800 mL/m2; thereafter, increasing IPV led to an increase in IPP. In
      the range of 600 to 1200 mL/m2 IPV, no significant increment of mean IPP was
      noted in infants (4.8 +/- 2.6 cm) and in children (9.6 +/- 2.1 cm). However,
      increasing the dialysate volume over 1000 mL/m2 induced an overincrement of the
      individual IPP value in most cases, and the rise of IPP was substantial when IPV
      rose from 1200 to 1400 mL/m2.

PMID- 8865931
TI  - Rhesus D genotyping in amniotic fluid.
AB  - Rhesus D genotyping by PCR of amniotic fluid offers a very valuable tool for
      prenatal care of Rhesus D-alloimmunized women. Misleading results have been
      reported for the method of Bennett et al. analysing the 3'-terminal end of the
      RhD gene. We have observed also problems with Rhesus D genotyping of DVI-variant
      samples in the assay of Simsek et al. utilizing size differences of intron 4
      between the Rhesus D and the Rhesus CcEe gene. We, thus, prefer to amplify two
      different regions including the 3'-terminal region of the Rhesus D gene to
      further minimize the very low risk of false-negative results. This rapid Rhesus D
      genotyping usually does not require more than 2 ml of amniotic fluid.

PMID- 8865932
TI  - Structure of antigens recognized by cold agglutinins.
AB  - At this time, three major groups of antigens recognized by cold agglutinins (CAs)
      are known: Iij antigens are defined by branched, linear, and branched and linear
      type 2 chains, respectively. They are protease- and sialidase-resistant. Whereas
      Ii antigens are developmentally regulated, j is expressed on newborn and adult
      erythrocytes in equal strength. The antigens of the Sia complex are biochemically
      related to the Iij antigens: they are sialylated type 2 chains. Consequently,
      they are protease resistant but sialidase-sensitive. Sia-l and Sia-b antigens are
      differentiation antigens, Sia-lb is not developmentally regulated. The structure
      of the Pr/Sa antigens is defined by the O-glycans of the glycophorins of the
      human red blood cell membrane. The immunodominant component is represented by N
      acetyl-neuraminic acid. Therefore, Pr/Sa antigens are protease-sensitive. With
      one exception (Pra), the antigens of this complex are also sialidase-sensitive.
      They are not developmentally regulated.

PMID- 8865933
TI  - Monoclonal antibodies: epitope specificity and typing of Dpartial cells.

PMID- 8865934
TI  - Effect of low ionic strength on anti-Pr reactions.
AB  - The effect of low ionic strength (LIS) on 28 anti-Pr, 20 anti-I and 20 anti-i
      cold agglutinins was investigated. The reaction of the anti-Pr CAs varies
      markedly. In most cases LIS has an enhancing effect. In some cases the thermal
      amplitude was widened so far that the reaction at 37 degrees C under LIS was
      stronger than at 0 degree C in PBS. With regard to the anti-Pr subspecificities
      anti Pr1, -Pr2 and -Pr3 or to the distinction of the immunodominant NeuNAc group
      (alpha a2,6- or alpha 2,3-bond) a correlation between these characteristics and
      the reaction in LIS could not be identified. The anti-I are not influenced by
      LISS, anti-i in a few cases. The reason for the variable reaction of the anti-Pr
      remains unclear. To further elucidate the LISS effect on anti-Pr, the
      contribution of the antibody structure should be regarded, but data for the use
      of H- and L-chain genes in anti-Pr are sparse. For compatibility testing in the
      routine laboratory, LISS-sensitive anti-Pr may play a role in disturbing the
      screening for RBC antibodies.

PMID- 8865935
TI  - Rapid detection of IgG subclasses on DAT positive RBC membranes by flow cytometry
      (FC).
AB  - Red blood cell (RBC)-bound IgG can cause hemolysis resulting, e.g. in severe
      cases of autoimmune hemolytic anemias (AIHA) or in hemolytic disease of the
      newborn (HDN). Serologic detection and differentiation of these antibodies are
      often difficult in cases of low antibody titers. We investigated 36 cases of poly
      and monospecific IgG-positive DATs by flow cytometry. The RBC samples were
      washed, diluted, and incubated with monoclonal antibodies directed against IgG1,
      IgG2, IgG3, and IgG4, respectively. Analysis was performed on a flow cytometer.
      Nine cases were negative for all 4 IgG subclasses, 8 cases were positive for
      IgG2, 5 for IgG1, 5 for IgG3, and 3 for all four subclasses. In 6 patients we
      found combinations of 2 or 3 subclasses (2 for IgG1 and IgG2, 1 for IgG1 and
      IgG3, 1 for IgG3 and IgG4, 1 for IgG1, IgG2 and IgG4, 1 for IgG1, IgG3 and IgG4).
      Serological differentiation revealed specific anti-bodies only in 3 cases (anti
      Lea, anti-Leb, anti-P1). The type of IgG subclass and the amount of RBC-bound IgG
      is relevant for the degree of in vivo RBC destruction. Flow cytometry provides a
      rapid, highly sensitive, cost efficient, and specific tool for IgG detection,
      including subgroups. CONCLUSIONS: We therefore recommend flow cytometric analysis
      to be integrated into the serological decision process as an additional method
      for serological problem cases.

PMID- 8865936
TI  - Quantitation of platelet glycoprotein mRNA using the polymerase chain reaction.

PMID- 8865937
TI  - Tantalum stents induce expression of GMP140 and GP53 on platelets after contact
      in an in vitro model.
AB  - Endovascular implantation of stents has become increasingly important to reduce
      acute complications and restenosis after percutaneous transluminal coronary
      angioplasty (PTCA). Nevertheless, the risk of stent related thrombosis still
      appears to be a limitation in this therapeutic approach. As platelets play a
      major role in thrombus formation, we examined platelets in an in vitro model by
      flow cytometry to assess the expression of activation-dependent epitopes caused
      by shear stress and contact to artificial surfaces of stents. Tantalum wire
      stents (n = 12) were placed in one of two parallel silicon tubing systems. Both
      systems were filled with citrated platelet-rich plasma (PRP) of healthy and drug
      free volunteers. After recalcification, aliquots of PRP were drawn via a three
      way faucet over a course of 10 min. For flow cytometric analysis monoclonal
      antibodies CD41a, CD42b, CD62p and CD63 were applied. Within 2 min after onset,
      the expression of CD62p (GMP140) and CD63 (GP53) increased in the tubing system
      with the stent. Over the course of 10 min, platelet activation progressively
      increased (CD62p p < 0.05 vs. control system without stent; CD63 p < 0.005 vs.
      control). Antigens CD41 a and CD42b did not show significant changes in both
      systems. Artificial surfaces and shear forces of stent meshes may contribute to
      the activation of platelets, thereby promoting the thrombotic potential. As an
      utmost sensitive diagnostic tool, flow cytometry may attribute to further
      improvement of material and design of stents.

PMID- 8865938
TI  - Improved plasma quality by Haemonetics PCS-2 using the centered core blow molded
      bowl.

PMID- 8865939
TI  - Self-sufficiency for plasma and plasma proteins in Norway.
AB  - Self-sufficiency has been achieved in Norway with regard to all major blood
      products even with the collection of only 41,906 units of whole blood and 2,586
      plasmapheresis sessions per million inhabitants (1994). Since 1989 the
      collaborative effort of the 'Norwegian Fractionation Project' has secured the
      self-sufficiency of virus-inactivated plasma and (high/ ultra-high purity)
      products of plasma proteins. Thus national self-sufficiency for plasma can be
      obtained by a combination of national guidelines, close collaboration to the
      clinicians, and a limiting plasmapheresis programme combined with the preparation
      of FFP from the majority of whole blood collections.

PMID- 8865940
TI  - In-line filtration of SAG-M red cell concentrates prepared in top/bottom or
      conventional bag systems.
AB  - SAG-M RCCs were prepared in triple conventional or quadruple top/bottom bag
      systems and filtered at +4 degrees C using the in-line filter system Leucoflex
      LCR 4 Macopharma after 16-24-30 h of storage. Postfiltration WBC content was
      determined by Nageotte hemocytometer counting. The mean WBC content of the units
      prepared in conventional bag systems and filtered was higher than that of the
      units prepared in T/B bag systems. The best results could be obtained in T/B RCCs
      stored for 24 h; potassium and hemolysis levels were also improved. The Leucoflex
      LCR 4 in-line filter T/B system can be recommended for application in the
      clinical routine by virtue of the effective leukocyte elimination.

PMID- 8865941
TI  - Immunocompetence of T lymphocytes during whole-blood storage.
AB  - In WB stored for 28 days at 4 degrees C the pattern of peripheral T-cell CD25 (IL
      2R) expression after polyclonal in vitro stimulation was examined. Flow
      cytrometic analysis was performed with lymphocytes after 72 h in culture with and
      without ConA using antibody against CD3 and CD25. In culture supernatants IL-2
      was determined. T-cells bearing the CD25 marker decreased with storage time, the
      mean fluorescence (i.e., number of IL-2R molecules per cell) remained rather
      stable. IL-2 concentrations peaked with stimulated cells which have been stored
      for 6 days. The low detectable levels of IL-2 in cultures of T-cells which have
      not been stored may reflect a much more efficient interplay of IL-2/IL-2R. Thus,
      even after longer periods of blood storage there are sufficient numbers of T
      cells which can be stimulated to excite preprogrammed effector functions, i.e.
      also a GVHD.

PMID- 8865942
TI  - Quantitation of circulating hematopoietic progenitor cells early after
      transplantation.
AB  - By multicolor flow cytometry CD34 positive blood progenitor cells (BPC) were
      determined by standard procedures before and after reinfusion. Measurements of
      circulating progenitor cells after transplantation lead to cell numbers that are
      considered together with reconstitution potential, especially with the number of
      transfused apheresis platelet concentrates after transplantation. Decreased
      concentrations of CD34 positive cells are associated with an increased frequency
      of platelet transfusions after transplantation.

PMID- 8865944
TI  - Improved automated bone marrow processing and enrichment of CD34+ cells by a
      large-volume apheresis procedure.
AB  - We investigated the efficacy of bone marrow (bm) processing by a large-volume
      apheresis procedure using a self constructed sixfold collection bag system for
      sequential cell collection and analysis for 5 pediatric patients. Quantitation of
      leukocytes (WBC), CD34+ cells and colony-forming cells (CFU-GM) within the single
      bags showed a relative time-dependent decrease of all cell fractions during
      leukapheresis, whereas the relative amount of mononuclear cells (MNC) droped only
      slightly. At the same time the large volume apheresis (6 x original bm-volume)
      clearly enhanced the absolute yield of CD34+ cells compared to the standard
      procedure (3 x bm-volume) for more than 20%. We conclude that large-volume
      apheresis for bm processing is an efficient technique to improve the yields of
      progenitor cells.

PMID- 8865943
TI  - Storage of peripheral blood stem cell samples alters flow cytometric CD34+
      results.
AB  - With the use of monoclonal antibodies against the CD34 antigen, flow cytometry
      (FC) permits rapid assessment of the quality of hematopoietic grafts. We examined
      PBSC samples (n = 40) to investigate possible influences of storage time and
      temperature on FC results. After cytapheresis, a sample of the PBSC product was
      collected and divided into 4 aliquots. Immediate analysis was performed on one
      aliquot. The other 3 specimen were stored for a) 24 h at room temperature (RT, 20
      +/- 2 degrees C), at room temperature with agitation and c) at +4 degrees C. For
      flow cytometric analyses, samples were labeled with two CD34 markers (HPCA-2,
      Becton Dickinson Corp. [BD], USA; QBend-10, Immunotech Corp. [IT], Germany).
      After 24 h CD34+ signals had decreased by 25.4% (BD) and 27.0% (IT) in average,
      when samples were stored at room temperature in comparison to the results
      obtained directly after cytapheresis (p < 0.05). At RT in combination with
      agitation, there was an increase in signal rates compared to baseline values,
      probably due to binding of CD34 antibodies to myeloid or non-viable cells (+ 9.2%
      [BD] and 11.2% [IT]). At a storage temperature of +4 degrees C, CD34+ events did
      not decrease significantly (-0.7% [BD] and -0.2% [IT]). Our data demonstrate that
      FC results may be influenced by temperature, agitation and storage time.

PMID- 8865945
TI  - Intravenous vs. oral iron supplementation during autologous blood donation.
AB  - Prior to hip replacement surgery, 197 patients (123 women, 74 men, age 18-86
      years) donated up to 4 units of blood once weekly if their hemoglobin
      concentrations exceeded 11.5 g/dl. They received an oral (200 mg iron sulfate
      daily) or intravenous (200 mg iron saccharate or 125 mg iron gluconate in 500 ml
      0.9% NaCl weekly) iron replacement. Correlating the number of donated blood units
      with the form of iron substitution, no effect of i.v. iron was seen in men. Women
      who received i.v. iron substitution were able to donate 4 units of blood more
      often than with oral iron.

PMID- 8865946
TI  - Influence of hemodilution on cefuroxime levels and bacterial contamination of
      intra- and postoperative processed wound blood during hip replacement.
AB  - MATERIALS AND METHODS: In a prospective randomized study we investigated the
      effect of hemodilution on cefuroxime levels and bacterial contamination of
      processed shed blood during hip arthroplasty. 10 patients received cefuroxime 1,5
      g as single shot prophylaxis before (group A), 10 after hemodilution (15 ml/KG)
      (group B). Cefuroxime levels in serum 1 h after administration, at the end of
      operation, after 12 h and in drainage-blood after 12 h were assessed by HPLC.
      Bacteriological study was performed from collecting bags (Vacufix), wound
      drainage blood and processed red blood cell concentrates, using pour plate
      technique and broth culture enrichment. RESULTS AND DISCUSSION: Mean
      concentrations of cefuroxime were higher in group B than group A, but differed
      not significantly. No bacterial contamination was found in collecting bags and
      wound drainages in both groups. Processed red cell concentrates in group B showed
      no growth. In group A, however, 3/10 were contaminated with < or = CFU/ml of
      coagulase-negative Staphylococcus, Staphylococcus epidermidis and
      Propionibacterium acnes. The differences between groups did not reach the level
      of statistical significance and could not be related to lower cefuroxime levels.
      No wound infection occurred in either group.

PMID- 8865947
TI  - HCV transmission through blood transfusion: are HCV-RNA titer in donor serum and
      genotype major determinants of infection outcome?
AB  - In this paper we report the results of a retrospective investigation on anti-HCV
      supplemental test positive blood donors from 1993 and 1994. 22 living recipients
      of blood/blood components from 15 donors were localized and enrolled in the
      study. Serum from these individuals were tested by serological assays and RT/PCR.
      HCV-RNA titer was determined for all positive donors. Genotyping was performed
      for all HCV-RNA positive individuals (donors and recipients). We observed that
      less than 50% of the recipients of previous donations from those positive donors
      did develop serological markers of HCV infection. HCV-RNA titers in donor's serum
      varied from 2 x 10(3) to 5 x 10(5) copies/ml but a direct correlation between
      viral RNA titer and the outcome of infection could not be established. Genotype
      investigation revealed 100% identity of genotypes within the pairs of
      donors/recipients. Genotype 1 b reached a prevalence of 75% within this group.

PMID- 8865948
TI  - Nerve abscess in children and adults leprosy patients: analysis of 145 cases and
      review of the literature.
AB  - The authors report on their experience of nerve abscess in leprosy. They have
      found that in the last 5 years there is a significant increase in this type of
      pathology, at a time when the total number of patients has decreased in adults.
      Nerve abscesses are, recently, noticed in a large number of children and
      teenagers. This was not the case 7-9 years ago. Abscesses were excised from one
      hundred forty-five nerves in one hundred and sixteen patients between May 1985
      and May 1994, out of which, 14 patients (12.6%) were operated during the period
      May 1985 to December 1989 and 102 (87.93%) in the period January 1990 to May
      1994. Children and teenagers account for 47% of all cases of nerve abscess in
      this series. The incidence of abscess in multiple nerves is high too in these
      groups. Abscess of cutaneous nerves is very common too (35% of cases) though
      rarely reported in the literature. There is a higher incidence of nerve abscess
      in male adults as compared to females. The authors believe that this sudden
      increase in neural pathology can be attributed, in part, to the extension of
      multidrug therapy (MDT) programmes without adequate infrastructure to detect and
      treat early neuritis.

PMID- 8865949
TI  - Calcification of peripheral nerves in leprosy.
AB  - A study conducted in 74 TT/TB patients, with gross thickening of nerves together
      with nerve abscess, showed calcification in 8 patients. Calcification was most
      common in the ulnar nerve followed by the lateral popliteal nerve. All eight
      patients were males with significantly longer duration of illness before start of
      treatment. Patients with late onset of nerve abscess were found to be more prone
      to calcium deposition in the nerves. Caseous pus of the abscess had high lipid
      content with raised cholesterol and cholesterol ester ratio to total lipids
      suggesting a dystrophic nature of calcification.

PMID- 8865950
TI  - Effectiveness of a high school alcohol misuse prevention program.
AB  - An alcohol misuse prevention curriculum for tenth-grade students was developed,
      implemented, and evaluated through twelfth grade with 1041 students from four
      school districts. The curriculum emphasized social pressures resistance training,
      immediate effects of alcohol, risks of alcohol misuse, and social pressures to
      misuse alcohol. There were desirable program effects on alcohol misuse prevention
      knowledge (p < 0.001), alcohol misuse (p < 0.02), and refusal skills (p < 0.09).
      Gender by occasion differences were found on alcohol use, alcohol misuse, and
      driving after drinking, with boys' rates increasing more than those of girls.
      Exposure to a sixth-grade, as well as the tenth-grade, program did not result in
      better outcomes. Despite high levels of alcohol use among high school students, a
      tenth-grade curriculum can result in some desirable effects. Creative approaches
      are needed, however, especially for boys who tend to use and misuse alcohol at
      rates that increase more steeply than those of girls.

PMID- 8865951
TI  - Differences in the serum levels of acetaldehyde and cytotoxic acetaldehyde
      albumin complexes after the consumption of red and white wine: in vitro effects
      of flavonoids, vitamin E, and other dietary antioxidants on cytotoxic complexes.
AB  - After the consumption of ethanol, acetaldehyde levels increase in the serum, and
      the serum develops a nondialyzable cytotoxic activity caused by the formation of
      unstable acetaldehyde-albumin complexes. The concentration of acetaldehyde in the
      serum and the cytotoxic activity in serum albumin 8.5 hr after six healthy
      volunteers began to drink 94 g of ethanol were significantly less when the
      ethanol was consumed as red wine than as white wine. The serum acetaldehyde was
      measured by a fluorigenic HPLC assay, and the cytotoxic activity in albumin was
      determined using two different assays based on dissimilar endpoints: (1)
      detachment of adherent A9 cells and (2) impairment of the ability of A9 cells to
      reduce tetrazolium. When serum obtained from five other healthy volunteers after
      the consumption of white wine was incubated at 37 degrees C for 3 hr with a
      number of dietary antioxidants at a concentration of 100 mumol/liter, the
      cytotoxicity of the albumin was markedly reduced. The antioxidants studied
      consisted of six flavonoids (kaempherol, fisetin, quercetin catechin, taxifolin,
      and coumarin) and three nonflavonoids (salicylic acid, tannic acid, and alpha
      tocopherol). In the cases of alpha-tocopherol, a statistically significant
      reduction of cytotoxicity was observed at a concentration of 10 mumol/liter. In
      addition, the cytotoxicity of artificially prepared acetaldehyde-albumin
      complexes was significantly reduced when such complexes were incubated with 50 to
      100 mumol/liter of kaempherol, fisetin, quercetin, coumarin or salicylic acid, or
      10 mumol/liter of alpha-tocopherol at 37 degrees C for 3 hr. Evidently, in vitro,
      flavonoid and nonflavonoid dietary constituents reduce the amount of unstable
      acetaldehyde-albumin complexes found in both postalcohol serum and in
      artificially produced acetaldehyde-albumin complexes. The difference in the
      amount of unstable acetaldehyde-albumin complexes found in serum after the
      consumption of red and white wine may therefore be caused by the higher
      concentration of antioxidants, including flavonoids, in red wine than in white
      wine. Because acetaldehyde and acetaldehyde-albumin complexes have been
      implicated in the pathogenesis of alcohol-mediated tissue damage, these data
      suggest that dietary antioxidants may influence the biological consequences of
      excess alcohol consumption.

PMID- 8865952
TI  - Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans.
AB  - 4-Methylpyrazole (4-MP), a potent inhibitor of alcohol dehydrogenase activity, is
      a candidate to replace ethanol as the antidote for methanol and ethylene glycol
      intoxications, because it has a longer duration of action and apparently fewer
      adverse effects. To study a probable mutual inhibitory effect between ethanol and
      4-MP on their elimination, two studies were performed in healthy human volunteers
      using double-blind crossover designs. In study A1 4-MP in the presumed
      therapeutic dose range of 10 to 20 mg/kg caused a 40% reduction in the rate of
      elimination of ethanol in 12 subjects given 0.5 to 0.7 g/kg of ethanol. These
      data suggest that such doses of 4-MP inhibit alcohol dehydrogenase activity in
      humans in vivo and would be effective at blocking methanol or ethylene glycol
      metabolism. In study B, ethanol (0.6 g/kg followed by 0.2 g/kg twice)
      significantly decreased the rate of elimination of 4-MP (5 mg/kg, given
      intravenously to four subjects). These moderate doses of ethanol also inhibited
      the rate of urinary excretion of 4-carboxypyrazole, the primary metabolite of 4
      MP in humans. Data suggest that ethanol inhibits 4-MP metabolism, thereby
      increasing the duration of therapeutic blood levels of 4-MP in the body. This
      mutual interaction may have clinical implications, because most self-poisoned
      patients have also ingested ethanol. Theoretically, methanol and ethylene glycol
      might also show such interactions with 4-MP.

PMID- 8865953
TI  - Verbal learning and memory in children with fetal alcohol syndrome.
AB  - Children with fetal alcohol syndrome (FAS) were administered the California
      Verbal Learning Test-Children's Version, a word list learning task that assesses
      immediate and delayed recall and recognition memory. When compared with matched
      control children, the children with FAS had difficulty learning and recalling the
      words after a delay period and tended to make an increased number of intrusion
      and perseverative errors. In addition, they had difficulty discriminating target
      words from distracter words and made more false-positive errors on recognition
      testing. Some of these deficits persisted even when mental age was controlled.
      The results suggest that children with FAS have profound verbal learning and
      memory deficits, and that some of these deficits cannot be accounted for even
      when mental age is considered. Furthermore, the results are consistent with
      deficits in encoding verbal information and impairment in response inhibition
      capabilities.

PMID- 8865954
TI  - Psychometric properties and validity of the obsessive-compulsive drinking scale.
AB  - Abstinent alcoholics' self-reports of distressing alcohol-associated thoughts and
      compulsions to drink were evaluated by the Obsessive-Compulsive Drinking Scale
      (OCDS). Exploratory and confirmatory factor analyses on separate subject samples
      revealed that subjects' OCDS responses were best described by four correlated
      dimensions: alcohol obsessions, alcohol consumption, automaticity, and
      interference due to drinking. The validity of this four-factor solution was
      supported by the pattern of associations with drinking and coping style measures.
      In particular, alcohol obsessions were positively associated with alcohol
      dependence and use of passive/ avoidant coping. Automaticity was positively
      associated with the intensity and salience of drinking, and inversely associated
      with use of active/approach coping, as well as abstinence duration. The obsession
      and automaticity subscales of the OCDS may be useful in evaluating cognitive
      motivational processes associated with recovery from alcoholism.

PMID- 8865955
TI  - Hostility is associated with a low prolactin response to meta
      chlorophenylpiperazine in abstinent alcoholics.
AB  - The prolactin response to the administration of serotonin agonists is an index of
      central nervous system serotonin (5HT) activity. This index is blunted in
      association with hostile aggression in personality-disordered individuals without
      substance abuse. We tested whether prolactin response to the partial 5HT agonist
      meta-chlorophenylpiperazine (MCPP) (0.35 mg/kg po) was associated with measures
      of trait hostility in alcoholics who were completing a 3-week rehabilitation
      program after medical detoxification. We also tested whether the same 5HT index
      differed in the group of alcoholics compared with the healthy volunteers. The
      prolactin response to MCPP was inversely associated with the main index of trait
      hostility and was similarly inversely associated with an index of depression.
      There was, however, no difference in neuroendocrine or temperature responses to
      MCPP between the alcohol-dependent group and the healthy volunteers.

PMID- 8865956
TI  - Biological markers of alcohol consumption and effect of calcitonin in
      nonalcoholic men: a prospective, double-blind study.
AB  - The objective of this study was to study the ability of biological markers of
      alcohol consumption in differentiating subjects below weekly consumption of 400
      or 600 g of absolute ethanol from those above, and to study the effect of
      intranasal calcitonin on alcohol drinking. A prospective 12-week double-blind
      study that used anonymous data collection with drinking diaries was done. The
      drug that was studied (calcitonin or placebo) was used during study weeks 5-8.
      This study was performed at the research unit of a university hospital. The
      subjects consisted of 59-nine men aged 26 to 57 years who considered themselves
      as regular but modest drinkers and were recruited by advertisements. The
      measurements were obtained from monthly questionnaires and daily anonymous
      diaries for alcohol drinking data, and biological markers of alcohol consumption
      (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl
      transpeptidase, beta hexosaminidase, and carbohydrate deficient transferrin). The
      results indicated intranasal calcitonin with a dose of 200 IU three times a week
      had no effect on alcohol use. All biological markers studied had only a modest
      ability to differentiate those with weekly alcohol consumption of 400 or 600 g or
      over from those below these limits. The areas under receiver operating
      characteristic (ROC) curve with the limit 400 g/week were 0.71 for aspartate
      aminotransferase, 0.61 for alanine aminotransferase, 0.74 for gamma-glutamyl
      transpeptidase, 0.68 for beta-hexosaminidase, and 0.78 for carbohydrate deficient
      transferrin. Respective numbers for the 600-g limit were more uniform. As
      evaluated by ROC analysis, carbohydrate deficient transferrin was the best
      biological marker to find men with weekly alcohol consumption over 400 g.
      Intranasal salmon calcitonin had no affect on alcohol drinking.

PMID- 8865957
TI  - Relationship between alcohol intake and immunoglobulin a immunoreactivity with
      acetaldehyde-modified bovine serum albumin.
AB  - Acetaldehyde, the main metabolite of ethanol, is a highly reactive species that
      reacts with macromolecules to produce unstable and stable adducts. Acetaldehyde
      modified proteins are immunogenic and have been detected in the liver and blood
      of alcoholics. Furthermore, antibodies reactive with acetaldehyde-modified
      proteins have been detected in the plasma of social drinkers and alcoholics.
      However, the class distribution of immunoglobulins reactive with modified
      proteins was different in the two groups, being predominantly immunoglobulin
      (Ig)M in social drinkers, but IgM and IgA in alcoholics. In this study, we
      demonstrate that heavy drinkers (alcohol intake > 130 g/week for females and 150
      g/week for males) also exhibit IgA reactivity with acetaldehyde-modified
      proteins. The IgA adduct-specific reactivity (IgA reactivity with acetaldehyde
      modified bovine serum albumin-reactivity with native bovine serum albumin) showed
      a moderate correlation with self-reported alcohol intake, but did not correlate
      with markers such as plasma transaminase, gamma-glutamyltransferase activity, or
      mean corpuscular volume. IgA adduct-specific reactivity had similar specificity
      to the conventional tests of alcohol abuse, but had higher sensitivity than the
      other tests, especially with heavy drinkers. Data presented herein demonstrate
      that elevated IgA reactivity with acetaldehyde-modified epitopes is associated
      with heavy drinking and is a potential marker for high alcohol intake.

PMID- 8865958
TI  - Carbohydrate-deficient transferrin as an indicator of drinking status during a
      treatment outcome study.
AB  - Biological markers of alcohol consumption have been used in both clinical and
      research settings to aid in the identification of relapse drinking. Although
      carbohydrate-deficient transferrin (CDT) has been shown to be a sensitive and
      specific marker for the identification of heavy drinkers, little data are
      available as to its utility as a marker for relapse drinking during treatment,
      particularly in comparison with the more widely used serum gamma
      glutamyltransferase (GGT). CDT and GGT were measured in 35 male alcoholics before
      entering, and every 4 weeks during, a 12-week outpatient treatment trial
      combining pharmacotherapy and cognitive behavioral therapy. CDT and GGT were
      again measured 14 weeks after completion of treatment. During the 12-week
      treatment period, CDT showed a significant difference in those individuals who
      abstained from drinking (30% decrease), compared with those who relapsed (10%
      increase). GGT decreased on average in all individuals, and the change from
      treatment entry did not differ significantly across the drinking outcome groups.
      The change in CDT, but not GGT, from study entry to termination, significantly
      correlated with total alcohol consumption during the trial. At the 14-week
      posttreatment, follow-up evaluation CDT showed about a 60% elevation and GGT
      showed a 30% elevation, on average, from study entry values in those individuals
      who had relapse drinking by self and/or collateral report. The change in both
      markers differed between those individuals who remained abstinent or relapsed
      during the poststudy period. In general, the change in CDT from pretreatment
      levels seemed more sensitive to drinking status during treatment and follow-up
      than GGT. This indicates that CDT may be more sensitive marker for evaluating
      drinking status during both clinical and research treatment trials.

PMID- 8865959
TI  - The natural history of outpatient alcohol and drug abuse treatment in a private
      healthcare setting.
AB  - Managed healthcare has had a major impact on the delivery of alcohol and drug
      abuse treatment services in the private setting, primarily by shifting patient
      enrollment from inpatient to outpatient treatment programs. The purpose of this
      study was to investigate the natural history of outpatient alcohol and drug abuse
      treatment in a private, nonprofit healthcare setting. Patient profiles at
      pretreatment, their attendance record in a 6-week outpatient program, and their
      outcome in the year after treatment were evaluated in 120 patients with a DSM-III
      R diagnosis of alcohol and/or cocaine dependence. There were 70 outpatients who
      successfully completed the program, and 50 who did not. Two subtypes of
      outpatient treatment failures were identified: S5 who prematurely left treatment
      against medical advice (n = 23), and S8 who attended treatment but continued
      heavy use of substances (Treatment Resistant, n = 27). A logistic regression
      revealed that younger age, multiple prior treatments, and employment problems
      were related to outpatient treatment failure. Outpatient failures did not
      immediately seek alternative treatment, and most of them continued heavy
      substance use in the year post-treatment: i.e., 82% vs. 43% successful completers
      (chi 2 = 13.8, df = 1, p < 0.01). Thus, there were a clinically relevant number
      of outpatient failures (42%), either because of lack of program attendance or
      continued substance use throughout treatment. These behaviors were related to
      continued heavy use of substances in the year after treatment.

PMID- 8865960
TI  - Efficacy of buspirone in alcohol dependence: a review.
AB  - The five published controlled studies on the effects of buspirone in alcoholism
      treatment are reviewed. They have been conducted mostly in alcoholics with
      comorbid anxiety. Significant differences in favor of the medication were
      observed in several psychopathological measures (anxiety, depression, hostility,
      interpersonal sensitivity, and global psychopathology). In only two studies were
      alcohol craving and consumption found influenced. Metaanalysis showed positive
      effects of buspirone on treatment retention, as well as on anxiety. It can be
      concluded that the main effect of buspirone in the treatment of alcoholism is not
      on ethanol consumption per se, but on associated psychopathological symptoms. A
      favorable safety profile and a lack of interaction with alcohol make buspirone a
      useful pharmacological adjunct in the treatment of alcoholism.

PMID- 8865961
TI  - Pharmacotherapies for alcohol problems: a review of research with focus on
      developments since 1991.
AB  - Research on medications to treat alcohol problems has flourished in the last 5
      years. Whereas before this time most projects focused on withdrawal agents, at
      least equal interest has now extended to drugs that may directly reduce urge to
      drink. The most promising medications in this regard are the opiate antagonists
      and acamprosate. Considerable attention has also been devoted to serotonergic
      agents. As aids to detoxification, pharmacologic agents that affect the multiple
      neural systems disrupted by acute alcohol withdrawal remain under active
      investigation. Significant progress is also being made in identifying medications
      to assist alcoholics suffering collateral psychopathology, especially depression
      and anxiety based disorders. Unfortunately, fewer gains have been realized in the
      development of medications to assist patients simultaneously dependent on both
      alcohol and illicit drugs. Also, research to develop amethystic agents remains in
      its very early stages.

PMID- 8865962
TI  - Voice 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 the victims 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- 8865963
TI  - Bulimia nervosa and substance dependence: association and family transmission.
AB  - Alcohol and drug use disorders are common among women with bulimia nervosa (BN)
      and their family members. However, it is not known whether there is a familial
      relationship between BN and substance use disorders. We compared 47 women with BN
      and 44 non-eating-disordered community control women, and their first-degree
      relatives (177 and 190, respectively). BN probands were stratified by the
      presence (43%) or absence (57%) of lifetime alcohol and/or drug dependence. The
      first-degree relatives of substance-dependent BN probands had significantly
      higher lifetime rates of alcohol/drug dependence (38%), compared with relatives
      of nonsubstance-dependent BN probands (10%) or relatives of community controls
      (18%). These data suggest that BN and substance dependence are transmitted
      independently in families.

PMID- 8865964
TI  - Differential effects of ethanol on feline rage and predatory attack behavior: an
      underlying neural mechanism.
AB  - Previous studies have shown that, at certain dose levels, ethanol can exert a
      powerful, facilitatory effect on aggressive behavior in both animals and humans.
      In the cat, however, it was discovered that ethanol differentially alters two
      forms of aggression that are common to this species. Defensive rage behavior is
      significantly enhanced, whereas predatory attack behavior is suppressed by
      ethanol administration. One possible mechanism governing alcohol's potentiation
      of defensive rage behavior is that it acts on the descending pathway from the
      medial hypothalamus to the midbrain periaqueductal gray (PAG)-an essential
      pathway for the expression of defensive rage behavior that uses excitatory amino
      acids as a neurotransmitter. This hypothesis is supported by the finding that the
      excitatory effects of alcohol on defensive rage behavior are blocked by
      administration of the N-methyl-D-aspartate antagonist alpha-2-amino-7
      phosphoheptanoic acid (AP-7) when microinjected into the periaqueductal gray, a
      primary neuronal target of descending fibers from the medial hypothalamus that
      mediate the expression of defensive rage behavior. Thus, the present study
      establishes for the first time a specific component of the neural circuit for
      defensive rage behavior over which the potentiating effects of ethanol are
      mediated.

PMID- 8865965
TI  - Ethanol ingestion inhibits cell-mediated immune responses of unprimed T-cell
      receptor transgenic mice.
AB  - This paper introduces a transgenic (Tg) mouse in which the majority of the CD4
      bearing T cells have T-cell receptors that react with ovalbumin (OVA) as a model
      for ethanol research. Although these Tg animals were bred onto the BALB/c genetic
      background, a strain generally considered to be nonpreferring in ethanol
      consumption, we determined that BALB/c mice would consume an ethanol-containing
      liquid diet, without significant mortality, and assessed alteration of specific
      immune responses. BALB/c, C57BL/6 (B6), or (BALB/c x C57BL/6)F-1 hybrid (CB6F1)
      mice were fed LED containing 35, 30, 25, or 20% ethanol-derived calories.
      Significant mortality (> 40%) was seen only in BALB/c and pronounced weight loss
      was seen in BALB/c, B6, CB6F1 mice when they were fed the diet containing the
      greatest ethanol concentration (LED35). Diets containing lesser amounts of
      ethanol did not cause mortality. Liquid diets containing > or = 30% ethanol
      derived calories significantly impaired the chicken gamma-globulin-specific
      delayed hypersensitivity responses in BALB/c, B6, and CB6F1mice without
      significantly affecting the humoral immune response to sheep red blood cells. We
      show that immunization of the Tg mice is not required for the development of a
      vigorous "delayed hypersensitivity" response to OVA or the I-Ad-restricted
      peptide OVA323-339 in mice fed standard solid lab chow or liquid control diet. In
      marked contrast, OVA Tg mice fed ethanol show a profound inhibition of this
      immune response, indicating that ethanol-induced inhibition of cell-mediated
      immunity occurs independently of antigen priming.

PMID- 8865967
TI  - Morphometric characteristics of human hepatocellular peroxisomes in alcoholic
      liver disease.
AB  - Hepatocellular peroxisomes harbor one of the metabolic pathways for ethanol
      metabolism (i.e., catalase in the presence of H2O2-generating enzymes). We
      studied the morphometric characteristics of these organelles in 26 biopsy samples
      of patients with different alcohol-induced lesions (12 with steatosis, 5 with
      hepatitis, and 9 with cirrhosis) and compared the findings with those obtained in
      seven control livers. All 33 human liver biopsy samples were stained for catalase
      activity to facilitate peroxisomal identification. Morphometric analysis of the
      peroxisomes was performed on calibrated electron micrographs. The numerical
      density of the peroxisomes was significantly increased to 183%, whereas the mean
      peroxisomal diameter (dcircle) revealed a significant decrease to 89%. This
      resulted in a normal volume density of the peroxisomal compartment, whereas the
      surface density was significantly induced. Peroxisomal shape was not different
      between alcoholic and control livers. When alcoholic livers were divided into
      three subgroups according to histopathological findings, similar morphometric
      results were obtained when compared with control livers, although significantly
      was sometimes lost. No differences in peroxisomal characteristics were found
      among alcoholic subgroups. The mean peroxisomal diameter per human liver
      (alcoholic and control) was inversely correlated to the numerical density. It is
      concluded that the peroxisomal adaptation in human alcoholic liver is such as to
      create an efficient environment for a presumably increased peroxisomal
      metabolism.

PMID- 8865966
TI  - Regulation of human monocyte functions by acute ethanol treatment: decreased
      tumor necrosis factor-alpha, interleukin-1 beta and elevated interleukin-10, and
      transforming growth factor-beta production.
AB  - We and others have previously shown that even acute ethanol exposure has the
      capacity to modulate immune functions, particularly monocyte functions. Herein,
      we tested the hypothesis that acute ethanol treatment inhibits inflammatory,
      while increasing inhibitory cytokine production in human blood monocytes that, in
      turn, could contribute to the overall immune abnormalities seen after alcohol
      use. Our data show that in vitro treatment of blood monocytes with a
      physiologically relevant dose of alcohol (25 mM) results in significantly
      decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin
      (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal
      enterotoxin B (SEB), 1 microgram/ml of SEB] or Gram-negative [lipopolysaccharide
      (LPS), 1 microgram/ml of LPS] origin both at the protein and mRNA levels. In
      contrast, acute ethanol treatment induces monocyte production of mediators with
      immunoinhibitory potential, including transforming growth factor-beta and IL-10.
      We further show that ethanol not only induces monocyte/macrophage (Mo) IL-10 and
      transforming growth factor-beta, but even augments bacterial (both LPS and SEB)
      stimulation-induced production of both of these cytokines. IL-10 is a potent
      inhibitor of Mo TNF alpha production. We found that ethanol-induced elevation in
      Mo IL-10 levels contributes to the decreased Mo TNF alpha production to bacterial
      challenge in ethanol-exposed Mo. However, mRNA levels for TNF alpha are
      downregulated as early as 1.5 hr after ethanol treatment, suggesting that ethanol
      likely has an IL-10 independent, direct effect on early signaling events of TNF
      alpha induction.

PMID- 8865968
TI  - Gender differences in phagocytic responses in the blood and liver, and the
      generation of cytokine-induced neutrophil chemoattractant in the liver of acutely
      ethanol-intoxicated rats.
AB  - Phagocytosis by circulating and liver-recruited polymorphonuclear leukocytes
      (PMNs) and Kupffer cells was studied in acutely ethanol-intoxicated, age-matched
      male and female rats. Acute ethanol intoxication in female rats is associated
      with a more effective phagocytic PMN response in the circulating blood, but with
      lower phagocytic activities by liver-recruited PMNs and Kupffer cells than in
      their male counterparts. Endotoxin [lipopolysaccharide (LPS)] treatment
      (consisting of a 90-min intravenous infusion of a nonlethal dose) of acutely
      ethanol-intoxicated male and female rats results in enhanced phagocytic responses
      in liver-sequestered PMNs and Kupffer cells, but not in circulating PMNs.
      However, the LPS challenge elicits a lesser phagocytic response in liver PMNs and
      Kupffer cells of female rats than in males. Significant gender differences exist
      in the extent of hepatic PMN infiltration in ethanol plus LPS-treated rats, which
      is paralleled by very similar differences in CD11b/c adhesion molecule expression
      in circulating PMNs and cytokine-induced neutrophil chemoattractant generation by
      hepatocytes and Kupffer cells. Taken together, these data indicate a smaller
      phagocytic response to fight infection in the liver of acutely alcohol
      intoxicated female rats, but also a mechanism to afford some protection against
      neutrophil-associated tissue injury.

PMID- 8865969
TI  - Effects of prenatal ethanol exposure on voltage-dependent calcium entry into
      neonatal whole brain-dissociated neurons.
AB  - The effect of prenatal ethanol exposure on voltage-dependent calcium entry into
      neonatal-dissociated neurons was studied. Dissociated whole brain cells were
      isolated from neonates of prenatally ethanol-treated (ET), pair-fed (PF) control,
      and ad libitum (AL) control groups and loaded with fura-2. Prenatal ethanol
      exposure resulted in a significant reduction of calcium entry into K(+)
      depolarized cells, compared with AL and PF control treatments. Initially, in
      dissociated cells from AL control animals, it was found that nifedipine (1
      microM), omega-agatoxin (100 nM), and omega-conotoxin (500 nM), to a much lesser
      extent, significantly inhibited the 45 mM KCl-stimulated calcium entry. To
      determine the inhibitory action of prenatal ethanol exposure on N-, P-, and L
      type voltage-dependent calcium channels, treatment of neonatal-dissociated
      neurons with different combinations of omega-conotoxin, omega-agatoxin, and
      nifedipine, respectively, was compared in the prenatal ethanol and control
      treatment groups. The inhibition of K(+)-stimulated increase in calcium entry by
      prenatal ethanol exposure was significantly less in the presence or absence of
      single antagonist conditions (ET < AL and PF). There was no apparent interaction
      of ethanol exposure and antagonist condition. However, the reduced calcium entry
      after prenatal ethanol exposure was superseded by the stronger inhibition in dual
      and triple antagonist conditions. The magnitude of the calcium response
      inhibition by the antagonist combinations was similar among the ET, PF, and AL
      groups. Thus, these results suggest that prenatal ethanol exposure decreases
      voltage-dependent calcium entry into neonatal-dissociated neurons in a manner
      that does not seem to involve the selective inhibition of any individual N-, P-,
      or L-type calcium channel.

PMID- 8865970
TI  - Serum and ascitic levels of soluble intercellular adhesion molecule-1 in patients
      with alcoholic liver cirrhosis: relation to biochemical markers of disease
      activity and alcohol intake.
AB  - The overexpression of intercellular adhesion molecule-1 (ICAM-1) has been shown
      to be involved in the pathogenesis of various necroinflammatory diseases,
      including alcoholic hepatitis. Shedding of this molecule from cell surfaces
      results in a circulating form, soluble ICAM-1 (sICAM-1). In this work, the serum
      and ascitic concentrations of sICAM-1 were studied in relation to clinical and
      laboratory data in patients with alcoholic liver cirrhosis of different disease
      activities. Elevated circulating concentrations of this adhesion molecule were
      found in all cirrhotic patients, the highest in those with superimposed severe
      alcoholic hepatitis, and the levels in regularly drinking cirrhotics without
      severe alcoholic hepatitis were likewise significantly higher than in those who
      had stopped drinking. The serum sICAM-1 concentration was best related to the
      serum AST activity, and also exhibited significant correlations with the
      prothrombin activity, serum bilirubin, albumin, peripheral leukocyte count.
      Maddrey's discriminant function value, Child grading, and antecedent alcohol
      consumption. Multivariate regression analysis revealed that the serum AST and
      prothrombin activities were independent predictors of the circulating sICAM-1
      concentration. The concentration of sICAM-1 in the uninfected ascitic fluid of
      cirrthotics was about seven times lower than that in the serum; the ratio of its
      ascitic and serum levels was lower than that of the ascitic and serum total
      protein concentrations. These data contradict a significant intraperitoneal
      production of the molecule. It is concluded that the serum sICAM-1 level may be
      useful as a marker for the current disease activity (the severity of underlying
      acute necroinflammatory reactions) in alcoholic liver cirrhosis.

PMID- 8865971
TI  - Mechanism of ethanol inhibition of NMDA receptor function in primary cultures of
      cerebral cortical cells.
AB  - Ethanol is a potent inhibitor of the function of the N-methyl-D-aspartate (NMDA)
      subtype of glutamate receptor in various neuronal preparations. In primary
      cultures of cerebellar granule cells, ethanol was suggested to interact with the
      glycine co-agonist site of the receptor by a mechanism involving protein kinase
      C. In the present study, the interaction of ethanol with various sites on the
      NMDA receptor was examined in primary cultures of cerebral cortical cells from
      embryonic rats. NMDA receptor function was determined by measuring increases in
      intracellular Ca2+ with fura-2 fluorescence. Ethanol inhibited the function of
      the NMDA receptor in cerebral cortical cells, but in contrast to the results in
      cerebellar granule cells, phorbol ester treatment did not inhibit the NMDA
      response, and ethanol did not alter the effect of glycine on NMDA receptor
      function. Ethanol also did not affect inhibition of the NMDA response by Mg2+ or
      dizocilpine. The results support the hypothesis that the mechanism of ethanol
      inhibition of NMDA receptor function can vary in neurons from different brain
      regions.

PMID- 8865972
TI  - Effects of ethanol on biotransformation of all-trans-retinol and all-trans
      retinal to all-trans-retinoic acid in rat conceptal cytosol.
AB  - Enzymatic catalysis of the oxidations of ethanol, all-trans-retinol (tretinol)
      and all-trans-retinal (t-retinal) were demonstrated in the cytosolic fractions of
      rat conceptal homogenates at day 12 of gestation. Products of the retinoid
      oxidation reactions were identified with HPLC by comparing elution times with
      those of authentic standard retinoids. NAD-dependent oxidations of each of the
      three substrates were demonstrable with assay conditions used; t-retinol and t
      retinal each were converted to readily detectable quantities of all-trans
      retinoic acid (t-RA). At 1.0 mM or higher concentrations, ethanol effectively
      inhibited the synthesis of t-RA from both t-retinol and t-retinal when adult
      hepatic cytosol was used as enzyme source. Approximately 70% and 40% inhibitions,
      respectively, were observed at 10 mM ethanol concentrations. By contrast, for the
      reactions catalyzed by rat conceptal cytosol (RCC) under the same experimental
      conditions, ethanol falled to inhibit significantly the conversion of either t
      retinol or t-retinal to t-RA at concentrations up to 1,000 mM. For the RCC
      catalyzed conversion of t-retinal to t-RA, increasing concentrations of ethanol
      (0 to 1.0 M) resulted in linear increases rather than decreases in quantities of
      t-RA generated. At a 2.0 M concentration of ethanol, the quantity of t-RA
      increased by > 50%. Significant inhibition of t-RA generation from t-retinal
      occurred only at extremely high (> 4.0 M) concentrations. The results indicated
      that ethanol was a very ineffective inhibitor of RCC-catalyzed synthesis of t-RA
      from either t-retinol or t-retinal. This contrasted strongly with effective
      inhibitory effects with adult hepatic cytosol as enzyme source. The results
      supported the concept that competitive inhibition of conversion of t-retinol to t
      RA in conceptal tissues is not a significant factor in ethanol-elicited
      embryotoxicity and dysmorphogenesis, at least in rodents. Mechanisms for the
      ethanol-induced increases in conversion of t-retinal to t-RA remain to be
      elucidated.

PMID- 8865973
TI  - Effect of chronic maternal ethanol administration on nitric oxide synthase
      activity in the hippocampus of the mature fetal guinea pig.
AB  - Nitric oxide is a novel messenger that is involved in neuronal cell-cell
      communication and seems to play a neurotrophic role in normal brain development.
      Chronic prenatal ethanol exposure can produce central nervous system (CNS)
      teratogenesis, in which one of the target sites is the hippocampus. The main
      objective of our study was to test the following hypothesis: chronic maternal
      administration of an ethanol dosage regimen that produces CNS teratogenesis
      decreases nitric oxide synthase (NOS) activity in the fetal hippocampus. The
      ontogeny of NOS activity in the hippocampus of the developing guinea pig was
      further elucidated at two prenatal and two postnatal ages. The effects of chronic
      maternal oral administration of 4 g of ethanol/kg maternal body weight/day,
      isocaloric sucrose and pair feeding, or water [given as two equally divided doses
      2 hr apart from gestational day (GD) 2 to GD 61] on body, brain, and hippocampal
      weights and hippocampal NOS activity were determined in the mature fetal guinea
      pig at GD 62 (term, about GD 68). NOS activity in the 25,000 x g supernatant
      fraction of hippocampal homogenate was measured using an optimized radiometric
      assay, based on the oxidation of L-[14C]arginine to L-[14C]citrulline. For the
      chronic ethanol regimen, the maternal blood ethanol concentration at 1 hr after
      the second divided dose on GD 57 was 157 +/- 45 mg/dl. Chronic maternal
      administration of ethanol decreased fetal body, brain, and hippocampal weights,
      compared with the isocaloric-sucrose/pair-fed and water treatment groups. The
      rate of L-[14C]citrulline formation and NOS activity in the fetal hippocampus
      were decreased in the ethanol treatment group, compared with the isocaloric
      sucrose/ pair-fed and water treatment groups. There was no difference in the rate
      of L-[14C]citrulline formation, NOS activity, and fetal hippocampal and body
      weights between the isocaloric-sucrose/pair-fed and water treatment groups;
      however, fetal brain weight was decreased in the isocaloric-sucrose group,
      compared with the water group. Data of this study support the research hypothesis
      by demonstrating that chronic maternal administration of ethanol decreases fetal
      hippocampal NOS activity that is correlated with restricted growth of this brain
      region.

PMID- 8865974
TI  - Chronic ethanol treatment reduces the responsiveness of the hypothalamic
      pituitary-thyroid axis to central stimulation.
AB  - The hypothalamic-pituitary-thyroid (HPT) axis functions abnormally in man and
      animals chronically exposed to ethanol. The most consistent observation in humans
      is that the thyrotropin response to thyrotropin-releasing hormone (TRH) is
      blunted. We have tested the hypothesis that chronic ethanol treatment in rats
      leads to a diminished responsiveness of the hypothalamus to central stimulation.
      Animals were maintained on 1 of 3 diets for 4 weeks: (1) laboratory chow and
      water provided ad libitum (chow-fed), (2) Sustacal chocolate liquid diet with
      vitamin mixture containing 5% (w/v) ethanol provided ad libitum (ethanol), or (3)
      Sustacal chocolate liquid diet with vitamin mixture containing sucrose
      substituted isocalorically (35%) for ethanol and provided in amounts matched to a
      weight-paired, ethanol-treated animal (pair-fed). At the end of 4 weeks, the
      animals were evaluated for their response to a single injection of ethanol (3
      g/kg, ip) and/or exposure to 5 degrees C. Chronic ethanol treatment produced an
      increase in TRH mRNA in neurons of the paraventricular nucleus and fully blocked
      the thyrotropic response to cold exposure. However, chronic ethanol-treated
      animals did not exhibit altered basal levels of triiodothyronine or thyrotropin,
      nor did they have an altered response to a single injection of ethanol. These
      data demonstrate that chronic alcohol exposure alters functioning of the
      hypothalamic-pituitary-thyroid axis at least in part by affecting TRH neurons of
      the paraventricular nucleus.

PMID- 8865975
TI  - Ethanol-induced inhibition of cell proliferation is modulated by insulin-like
      growth factor-I receptor levels.
AB  - Ethanol inhibits the tyrosine autophosphorylation of the insulin-like growth
      factor (IGF)-I receptor, an action that correlates with the inhibition of IGF-I
      stimulated cell proliferation [J. Biol. Chem. 268:21777-21782 (1993)]. In the
      current study, the IGF-I-dependent proliferation of mouse BALB/c3T3 cells was
      completely inhibited by ethanol, but the growth of BALB/c3T3 cells that
      overexpress the IGF-I receptor (p6 cells) was only partially inhibited by ethanol
      BALB/ c3T3 cells that simultaneously overexpress both the IGF-I receptor and IGF
      I were insensitive to growth inhibition by ethanol. In p6 cells, increasing
      concentrations of IGF-I overcame the inhibition of IGF-I receptor tyrosine
      autophosphorylation in the presence of ethanol. The importance of the IGF-I
      receptor as a specific target for ethanol was further investigated in C6 rat
      giloblastoma cells that respond mitogenically to both epidermal growth factor
      (EGF) and IGF-I. The mitogenic response of C6 cells to EGF was abrogated in cells
      expressing antisense mRNA to the IGF-I receptor. Thus, EGF action in these cells
      is dependent on activation of an IGF-I/IGF-I receptor autocrine pathway. Indeed,
      EGF stimulated an increase in IGF-I receptor levels by more than 100%. Ethanol
      completely inhibited the proliferation of C6 cells in response to either EGF or
      IGF-I. However, ethanol did not directly interfere with EGF receptor function,
      because EGF-induced cell proliferation was unaffected by ethanol when added
      exclusively during a 1-hr exposure to EGF. Ethanol did not interfere with the EGF
      induced increase in IGF-I receptor expression. The addition of both EGF and IGF-I
      overcame the inhibitory action of ethanol. In conclusion, the potency of ethanol
      as an inhibitor of IGF-I-mediated cell proliferation correlates with the level of
      IGF-I receptors. In contrast to its effect on the IGF-I-receptor, ethanol has no
      direct effect on EGF receptor activation.

PMID- 8865976
TI  - Second-trimester serum fluorescence polarization in patients who subsequently
      develop pregnancy-induced hypertension.
AB  - To determine whether the midtrimester serum lipid profile, as expressed by
      fluorescence polarization (FP) values, is decreased in patients who subsequently
      develop pregnancy-induced hypertension (PIH). Stored serum samples of
      normotensive patients who had undergone midtrimester biochemical screening for
      Down's syndrome were used in this case-control study. Forty patients who
      subsequently developed PIH comprised the study group, and were divided into
      subgroups with proteinuric PIH (P-PIH, n = 18) and those with nonproteinuric PIH
      (NP-PIH, n = 22). Sixty randomly selected patients who remained normotensive
      throughout pregnancy comprised the control. Serum total cholesterol (CL) and
      triglycerides (TG) were determined using enzymatic colorimetric kits. FP values
      were determined by optical microviscosimeter. Both study subgroups had
      significantly lower FP values and higher TG concentrations than the control
      group. Total CL concentrations were slightly higher in the P-PIH subgroup. There
      were no differences in mean. Total CL or TG concentrations or mean FP values were
      found between those patients who developed mild and severe PIH. Using FP value
      cutoff points of 0.250, 0.245, and 0.240 sensitivity was 95%, 90%, and 78%,
      respectively, in detecting patients who subsequently developed PIH. Midtrimester
      serum FP values may have some predictive value for the development of P- and NP
      PIH.

PMID- 8865977
TI  - Influence of neonatal idiopathic respiratory distress syndrome on serum enzyme
      activities in premature healthy and asphyxiated newborns.
AB  - Elevated serum aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH),
      and hydroxybutyrate dehydrogenase (HBDH) activities are highly predictive for the
      development of hypoxia-related neurologic disorders in asphyxiated newborns.
      Little is known about the influence of the idiopathic respiratory distress
      syndrome (IRDS) on the serum profile of these enzymes. In a prospective study we
      measured ASAT, LDH, and HBDH activities in asphyxiated newborns with (n = 12) and
      without (n = 12) IRDS as well as non-asphyxiated newborns with IRDS (n = 16).
      Blood samples were taken serially at five fixed times: 0 (cord), 12, 24, 72, and
      144 hours postpartum. Whereas both study groups of asphyxiated newborns showed
      significantly elevated enzyme activities as compared with the non-asphyxiated
      controls, the fundamental influence of perinatal hypoxic-ischemic events on
      neonatal serum enzyme profiles and activities of all three enzymes was not
      significantly altered by the development of IRDS. Therefore, the predictive value
      of these enzymes for the development of neurologic disorders in asphyxiated
      newborns is not adversely affected by the development of an immediately and
      effectively treated IRDS. It is concluded that elevated ASAT, LDH, and HBDH
      activities can be used as predictors for neurologic disorders in asphyxiated
      newborns even in the presence of IRDS.

PMID- 8865978
TI  - Plasma immunoreactive endothelin-1 concentrations in infants with persistent
      pulmonary hypertension of the newborn.
AB  - Plasma concentrations of endothelin-1 (ET-1) have been reported to be elevated in
      children and adults with pulmonary hypertension. We hypothesized that infants
      with persistent pulmonary hypertension of the newborn (PPHN) have elevated plasma
      concentrations of ET-1. Plasma concentrations of immunoreactive-endothelin-1 (ir
      ET-1) were measured using a radioimmunoassay in 20 infants with PPHN and 20
      normal term infants. Mean birthweight and gestational age of the infants were
      comparable in the two groups. The mean plasma ir-ET-1 concentrations were
      significantly elevated in neonates with PPHN compared to those of normal term
      infants (2.04 +/- 0.30 versus 1.04 +/- 0.29 pg/mL, p = 0.02). A linear regression
      analysis demonstrated a significant relationship between ir-ET-1 concentrations
      and alveolar-arterial oxygen gradient (r = 0.49, p = 0.02) and mean airway
      pressure (r = 0.49, p = 0.02). There was also a significant correlation between
      ir-ET-1 concentrations and duration of extracorporeal membrane oxygenation among
      infants with PPHN (r = 0.44, p = 0.05). We conclude that plasma ir-ET-1
      concentrations are elevated in infants with PPHN. The presence of elevated ir-ET
      1 concentrations and their positive correlation with disease severity suggests
      that ET-1 may serve as a marker of the disease severity in these infants.
      However, further studies are needed to elucidate the role of ET-1 in the
      pathophysiology of PPHN.

PMID- 8865979
TI  - Adenosine for the treatment of paroxysmal supraventricular tachycardia in full
      term and preterm newborn infants.
AB  - Adenosine has been approved for intravenous use for paroxysmal supraventricular
      tachycardias (SVT) in adults and children. However, effectiveness and safety of
      intravenous adenosine in preterm infants are not well established. Thirteen
      episodes of SVT in three preterm and two full-term neonates were treated with
      intravenous adenosine. All had narrow QRS tachycardia at 230 to 260 beats/min.
      Adenosine prepared as a sterile 1 mg/mL solution was given as an intravenous
      bolus starting at 0.05 mg/kg, and increased by 0.05 mg/kg until tachycardia was
      terminated. Termination of tachycardia was achieved within 12 to 25 seconds in
      all patients. In one, termination of SVT was followed by temporary suppression of
      the sinus node, followed by resumption of normal sinus rhythm. No other side
      effects were noted. Adenosine is a safe and effective agent for treating preterm
      infants with SVT. However, further investigation of adenosine in this group of
      patients is warranted.

PMID- 8865980
TI  - Midtrimester genetic amniocentesis of a twin gestation complicated by immediate
      severe fetal bradycardia with subsequent associated fetal anomalies.
AB  - We present an unusual complication of midtrimester genetic amniocentesis of a
      monochorionic twin gestation in which prolonged fetal bradycardia of 60 to 80
      beats per minute sustained over two hours was associated with multiple subsequent
      fetal anomalies. These included: microcephaly, bilateral closed-lip
      schizencephaly, duodenal atresia, and complete paresis of the left upper
      extremity. Etiology of the fetal bradycardia was unclear. Fetal hemorrhage was
      not visualized despite targeted, continued real-time ultrasonography and was
      therefore considered an unlikely etiology. Although the bradycardia and
      associated hypoperfusion could alone explain the fetal outcome, destabilization
      of hemodynamics of a communicating vessel, resulting in a possible (although
      unproven) acute twin-twin transfusion induced at the time of amniocentesis due to
      decreased intra-amniotic pressure in association with a velamentous umbilical
      cord insertion could have led to this unusual occurrence.

PMID- 8865981
TI  - A retrospective analysis of the effect of antenatal steroid administration on the
      incidence of respiratory distress syndrome in preterm twin pregnancies.
AB  - Respiratory distress syndrome (RDS) is the major cause of morbidity and mortality
      in preterm twin deliveries. Therapy with corticosteroids has been shown to reduce
      the incidence of RDS in preterm singleton gestations but similar reductions in
      twin pregnancies have not been demonstrated. Maternal and neonatal medical
      records were reviewed from twins delivered between 24 to 34 weeks gestation over
      the period of January 1, 1990 to December 31, 1994. Twenty-one pairs of twins
      received optimal steroid treatment defined as the use of two 12 mg doses of
      betamethasone, with birth occurring between 24 hours and 7 days after the first
      dose. Sixty-three pairs received no treatment. The mean gestational age at
      delivery was 29.9 +/- 2.6 weeks. No decrease was seen in the incidence of RDS
      (optimal steroid 70.7% versus no treatment 68.0%, unadjusted odds ratio [OR]
      1.14, 95% confidence interval [CI] 0.49 to 2.65). Multivariate logistic
      regression showed no statistical difference in the incidence of RDS in the
      optimal steroid compared to the no treatment group (adjusted OR 0.63, 95% CI 0.2
      to 1.95). No statistical differences were noted in the incidence of mechanical
      ventilation (58.6% versus 55.4%, p = 0.83), median duration of intubation (5.0
      versus 5.0 days, p = 0.47), the median maximum inspiratory pressure requirements
      (20.0 versus 22.0 mm Hg; p = 0.15) in the optimal treatment versus no treatment
      group, respectively. The current regimen of antenatal corticosteroids utilized in
      twin pregnancies does not reduce the incidence of RDS.

PMID- 8865982
TI  - Prenatal diagnosis and perinatal aspects of abdominal wall defects.
AB  - We retrospectively reviewed 27 cases of omphalocele and 15 cases of gastroschisis
      occurring among 62, 572 deliveries between 1987 and 1994. All cases had undergone
      prenatal sonographic examinations at a mean gestational age of 28 weeks. In cases
      of omphalocele, 59.3% (16/27) of fetuses were associated with multiple
      malformations and 16% (4/25) had chromosomal abnormalities. Among the 4 cases
      with an abnormal karyotype, three cases were associated with extracorporeal
      livers and two cases were associated with umbilical cord cysts. Prenatal
      ultrasound examinations during the second and third trimesters were able to
      detect 66.7% (18/27) of the cases of omphalocele and 66.7% (10/15) of the cases
      of gastroschisis. Failure in correctly diagnosing abdominal wall defects by
      prenatal ultrasound occurred mostly in cases associated with small defects,
      ruptured omphalocele, multiple fetal anomalies, intrauterine fetal death, twin
      pregnancies, or cases referred in late gestation. A comparison of perinatal data
      between omphalocele and gastroschisis reveals fetuses with omphalocele carry
      higher risks of associated malformations, chromosomal abnormalities, prematurity,
      and neonatal death. Although fetuses with gastroschisis have higher incidences of
      oligohydramnios and small for gestational age, the fetal prognosis after
      pediatric surgery is good.

PMID- 8865983
TI  - Low baseline oxygenation predisposes preterm infants to mixed apneas during
      inhalation of 100% oxygen.
AB  - We have shown previously that administration of 100% O2 to preterm infants
      induces an apnea which in about 20% of cases has an obstructive component. The
      obstruction occurred during the longer apneas. In the present study, we tested
      the hypothesis that the appearance of obstruction in longer apneas depends on the
      baseline oxygenation. Sixteen preterm infants were studied in quiet sleep
      (birthweight 1435 +/- 93 g [mean +/- SEM], study weight 1711 +/- 90 g,
      gestational age 30 +/- 1 weeks, and postnatal age 26 +/- 5 days) at various
      baseline oxygenations. A flow-through system was used to measure ventilation and
      alveolar gases. Respiratory efforts in the absence of flow were detected using
      chest and abdominal displacements or diaphragmatic electromyography. Each infant
      inhaled 15%, 21%, or 25% O2 for 5 minutes (control period) followed by 100% O,
      for 2 minutes. Baseline alveolar PO2, O2 saturation and transcutaneous PO2
      increased during inhalation of 15%, 21%, and 25% O2, respectively. The immediate
      decrease in ventilation with 100% O2 was 52% on 15% O2, 20% on 21% O2, and 16% on
      25% O2 (p < 0.001); this was associated with an apnea in all cases. The mean
      length of apneas during 100% O2 was 37 seconds on 15% O2, 19 seconds on 21%, and
      11 seconds on 25% (p < 0.01). Twelve infants (75%) developed mixed obstructive
      apneas in response to 100% O2 when breathing 15% O2 during control period, three
      (19%) when breathing 21% O2, and none had mixed apnea when breathing 25% O2
      during control period (p < 0.05). These findings suggest that lower baseline
      oxygenation predisposes to long mixed apneas. We speculate that the peripheral
      chemoreceptors, uniquely active in the small preterm infant with relatively low
      O2 tension, when suppressed by an increase in oxygen tension, trigger a central
      inhibition with loss of upper airway muscle tone. This is more pronounced when
      the baseline oxygen tension is lower, leading to more prolonged apnea and
      increased probability of obstruction.

PMID- 8865984
TI  - Embolic stroke in a pregnant patient with a mechanical heart valve on optimal
      heparin therapy.
AB  - A 28-year-old woman with a mechanical aortic heart valve experienced an embolic
      stroke in early pregnancy after her anticoagulation therapy was changed from
      warfarin to heparin. This occurred despite use of a subcutaneous heparin infusion
      pump and optimal anticoagulation. Thromboembolism can occur in pregnant patients
      with mechanical heart valves despite optimal heparin therapy.

PMID- 8865985
TI  - Effect of intrapartum use of oxytocin on estimated blood loss and hematocrit
      change at vaginal delivery.
AB  - We hypothesized that exogenous oxytocin given for labor induction or augmentation
      results in a greater blood loss at vaginal delivery compared with spontaneous
      labor. Second, we theorized that duration of exposure, and maximum or final
      dosage of oxytocin, would be positively correlated with blood loss. We
      retrospectively studied records of 111 women undergoing labor induction or
      augmentation by oxytocin infusion along with those of 76 women who had
      spontaneous labor. The outcomes evaluated included clinically estimated blood
      loss (EBL), and a change of hematocrit from admission to postpartum. These were
      further compared to duration and dosage of oxytocin infused. A combination of chi
      square and analysis of variance were used to compare the study group with the
      controls. Regression analysis was used to evaluate possible relationships within
      the study group. The demographics of the study group who received oxytocin were
      similar to those of the control group, with the exception of the percent who
      received an epidural (77% versus 29%, p < 0.0001) and length of labor (381 versus
      277 min, p < 0.001). There was no demonstrated relationship between oxytocin use
      and EBL or hematocrit change. Within the study group of 111 patients, there was a
      statistically significant increase in EBL (p < 0.01) and hematocrit change (p <
      0.0003) with increasing maximum dose of oxytocin. In addition, hematocrit change
      was greater with an increase in both duration (p < 0.001) and final dose of
      oxytocin (p < 0.0003). No relationship was demonstrated between exogenous
      oxytocin administration and increased blood loss, in a group of patients matched
      for variables other than spontaneous or oxytocin exposed labors. However, among
      those patients who received oxytocin, there was a correlation between amount of
      oxytocin exposure and blood loss. The initial hypothesis compared means between
      the two groups; however, the latter hypothesis sought to correlate increased
      exposure to oxytocin with increasing blood loss as measured by duration, maximum,
      and final dose.

PMID- 8865986
TI  - Response to dexamethasone in ventilated preterm infants: effect of radiographic
      subtype of chronic lung disease.
AB  - We compared the response to prolonged treatment with dexamethasone in two groups
      of ventilated preterm infants: one whose chest radiographs showed homogenous
      opacity, and one whose radiographs showed cystic changes and hyperinflation.
      Forty-nine infants were treated with dexamethasone for 42 days, beginning when
      they were 15 to 27 days old, had no evidence of sepsis or patent ductus
      arteriosus, and had experienced no decrease in ventilator support for 24 hours.
      Forty-nine controls were selected who met these criteria for dexamethasone
      treatment. All had birthweights of 500 to 1250 g. Two radiographs made between 14
      and 28 days of age were reviewed. Among infants with homogeneous opacity (19
      dexamethasone, 26 controls), dexamethasone was associated with fewer days on
      assisted ventilation (median [interquartile range]: 7 [3-11] versus 23 [9-40]; p
      = 0.001). Among those with cystic changes and hyperexpansion (30 dexamethasone,
      23 controls), no difference was found between dexamethasone treated infants and
      controls (17 [7-34] versus 32 [16-47]; p = 0.9). Thus, the effect of
      dexamethasone on days of ventilation was attenuated in infants with cystic
      changes and hyperinflation.

PMID- 8865987
TI  - Successful pregnancy after combined renal-pancreas transplantation: a case report
      and literature review.
AB  - A long-standing history of insulin-dependent diabetes mellitus can result in
      multiple organ damage. We present a case of successful pregnancy in a patient who
      underwent combined renal-pancreas transplantation for end-stage renal disease due
      to diabetic nephropathy. A 29-year-old white gravida 7, para 2 female was
      diagnosed with diabetes mellitus at age 7. She was well controlled with insulin
      until age 21. She developed complications of diabetes mellitus which included
      retinopathy resulting in legal blindness, nephropathy resulting in end-stage
      renal disease, and chronic hypertension. Following nine months of dialysis she
      underwent a combined renal-pancreas transplant. She subsequently became pregnant
      21 months after transplantation and delivered a healthy male at 35 1/2 weeks
      gestation. Renal-pancreas transplant recipients who become pregnant may be at an
      increased risk for adverse outcome. We present a successful pregnancy outcome in
      a combined transplant recipient who had a prior poor obstetrical history.

PMID- 8865988
TI  - Analysis of allelic structures at the D7S21 (MS31A) locus in the Japanese, using
      minisatellite variant repeat mapping by PCR (MVR-PCR).
AB  - To sample the diversity of allelic structures at the D7821 (MS31 A) locus in the
      Japanese, allele-specific minisatellite variant repeat mapping using polymerase
      chain reaction (MVR-PCR) was performed on genomic DNA from a number of Japanese
      individuals. Three polymorphic positions in the MS31A 5' flanking DNA were typed
      from 214 un related Japanese, and the distribution of haplotypes was analysed.
      Allele-specific MVR-PCR using primers that discriminate between different alleles
      at these polymorphic positions in heterozygous individuals, allows single alleles
      to be mapped from genomic DNA in approximately 80% of Japanese. 149 Japanese
      alleles have been mapped to date and all of them, except for two pairs of
      indistinguishable alleles, have different internal structures. More than half of
      the mapped alleles showed similar regions of internal structure to other alleles
      and were classified into groups on this basis.

PMID- 8865989
TI  - The human complement C8G gene, a member of the lipocalin gene family:
      polymorphisms and mapping to chromosome 9q34.3.
AB  - Complement component C8 is a plasma glycoprotein consisting of three nonidentical
      polypeptide chains (alpha, beta, gamma) which are encoded by three separate genes
      (C8A, C8B, C8G). The gamma chain whose functional role remains undefined is not
      related to any other complement protein but is a member of the lipocalins, a
      family of proteins that bind small hydrophobic ligands. The present report
      describes the first known polymorphisms for the human C8G gene, namely one
      polymorphic site in exon 1 (207T/G) and two polymorphic sites in intron 1 (213 +
      37G --> A; 213 + 65del3). Specific typing can be performed using simple
      polymerase chain reaction-based assays. C8G genotyping in eight CEPH reference
      families demonstrated that C8G is closely linked to a series of marker loci
      located in the most telomeric region of chromosome 9q. Multipoint analysis placed
      C8G with 1000:1 support distal to D9S207. C8G is thus located at 9q34.3.
      Remarkably, this chromosomal region contains at least four other lipocalin genes.

PMID- 8865990
TI  - Phylogenetic analysis of mtDNA lineages in South American mummies.
AB  - Some studies of mtDNA propose that contemporary Amerindians have descended from
      four haplotype groups, each defined by specific sets of polymorphisms. One recent
      study also found evidence of other potential founder haplotypes. We wanted to
      determine whether the four haplotypes in modern populations were also present in
      ancient South American aboriginals. We subjected mtDNA from Colombian mummies
      (470 to 1849 AD) to PCR amplification and restriction endonuclease analysis. The
      mtDNA D-loop region was surveyed for sequence variation by restriction analysis
      and a segment of this region was sequenced for each mummy to characterize the
      haplotypes. Our mummies exhibited three of the four major characteristic
      haplotypes of Amerindian populations defined by four markers. With sequence data
      obtained in the ancient samples and published data on contemporary Amerindians it
      was possible to infer the origin of these six mummies.

PMID- 8865991
TI  - Multiple founder haplotypes of mitochondrial DNA in Amerindians revealed by RFLP
      and sequencing.
AB  - The mitochondrial DNA (mtDNA) of 139 individuals from eight tribes which belong
      to four linguistic groups of the Brazilian Amazon Region was studied both by RFLP
      and by sequencing of the D-loop region. RFLP analysis showed that 41 haplotypes
      (29%) belonged to haplogroup A, 39 (28%) to haplogroup B, 38 (27%) to haplogroup
      C, 19 (14%) to haplogroup D, and 2 (< 2%) could not be assigned to any of the
      four haplogroups. Among the 92 individuals analyzed by direct sequencing of the D
      loop region, we observed 43 different haplotypes defined by 48 polymorphic
      points, while one haplotype could not be assigned to any of the clusters
      previously described. Joint analysis of data obtained by RFLP and by sequencing
      of mtDNA demonstrated that, regardless of the method of analysis, the mtDNA
      haplotypes of contemporary Amerindians cluster into four groups, similar to those
      previously described, even though 7% of the total sample or 12% of the haplotypes
      have discrepancies between results obtained by RFLP and sequencing. In addition
      to supporting the prevalence of four major haplogroups among contemporary
      Amerindians, our data are compatible with multiple founder haplotypes in each
      haplogroup, based on: i) a high prevalence of unusual haplotypes: ii) presence of
      multiple polymorphic sites shared by different haplogroups; iii) relative
      differences in nucleotide diversity based on RFLP or sequencing within the
      different haplogroups.

PMID- 8865992
TI  - Genetic relationship between the Canary Islanders and their African and Spanish
      ancestors inferred from mitochondrial DNA sequences.
AB  - Nucleotide sequences of the hypervariable segment I of the control region of the
      mtDNA were determined in 101 individuals: 54 Canary Islanders, 18 North African
      Berbers, 18 Spanish mainlanders and 11 sub-Saharan Guineans. In spite of the fact
      that only members of the Fang tribe were analysed, nucleotide diversity in
      Guineans (theta x 100 = 2.33) is one of the highest found in African populations.
      Estimates of genetic contribution to the Canarians from their putative parental
      populations based on mtDNA (43.25 +/- 1.38% Berbers, 35.54 +/- 0.55% Spanish,
      21.21 +/- 1.92% Guineans) showed an important North African substrate. These
      mtDNA results, when compared with data based on nuclear markers, point to a
      strong male female asymmetry, 75% of the Spanish nuclear contribution was due to
      males and practically all the Berber and Guinean was due to females. These
      results are in agreement with the way that the Canary Islands were conquered.
      Pairwise difference distributions in Guineans and Berbers are compatible with the
      model of populations in expansion. Departures from a Poisson distribution for the
      Canarians and Spanish can be explained by admixture and the way of sampling
      respectively.

PMID- 8865994
TI  - Pairwise analysis of radiation hybrid mapping data.
AB  - Two point lod scores are widely used in pedigree analysis as they provide a fast
      and efficient method of establishing linkage. Groups of markers that lie in close
      proximity to one another can be formed by admitting any locus that is linked to
      at least one existing member of the group with lod score greater than some
      predetermined value. It seems natural to extend this technique to Radiation
      Hybrid Mapping both for constructing groups of tightly linked loci that may then
      be analysed using more powerful statistics and as a method of ordering in its own
      right. A general extension of two point analysis is derived and the problems
      associated with radiation hybrid data are discussed. In particular, the
      additional parameters representing the probabilities of different fragments being
      retained (which have no parallel in classical linkage analysis) lead to a range
      of estimators of the breakage probability, O, which have equal and maximal
      likelihood. Ways of circumventing this problem are discussed along with the
      potential errors they introduce. Importantly the ambiguity in estimation of theta
      is not carried through to the lod score as this depends only on the maximum value
      of the likelihood and not on the particular value of theta at which it occurs.
      Thus even though two point analysis fails to provide robust estimates of either
      breakage probabilities or the distance between loci, it represents a simple and
      effective method of constructing linkage groups that may be analysed with more
      powerful statistical methods. This is particularly important given the large
      number of microsatellites, ESTs and candidate genes currently being typed on
      radiation hybrids.

PMID- 8865993
TI  - Genetic diversity in the Iberian Peninsula determined from mitochondrial sequence
      analysis.
AB  - We have analysed 302 bp of the first hypervariable region of the mitochondrial D
      loop in 271 individuals from different regions of the Iberian Peninsula and 85
      individuals from Algeria. The Basque population is significantly different from
      neighbouring populations in terms of overall levels of diversity. This is because
      the majority of sequences in the Basques are restricted to the lineage group
      defined by the CRS (Cambridge Reference Sequence) and its derivatives although,
      like other Iberian populations, they showed a unimodal distribution of pairwise
      sequence differences. The timing of divergence of populations within Iberia
      points to a shared ancestry of all populations in the Upper Palaeolithic. Further
      genetic subdivision is apparent in Catalonia and Andalusia, with increased
      genetic diversity in the latter. Lineage diversity comparisons of Iberian
      populations with European (Tuscan) and North African (Algerian) populations shows
      the Iberian Peninsula to be more similar to other European populations, although
      a small number of Iberian lineages can be traced to North Africa.

PMID- 8865995
TI  - On calculating posterior probability of linkage.

PMID- 8865996
TI  - Power and caring: a dialectic in nursing.
AB  - The tension between power and caring in nursing is evident through the volume of
      nursing literature related to power and powerlessness and through nurses'
      discomfort with notions of power. A dialectical examination of the concepts of
      power and caring reveals that at one level they appear to be polar opposites.
      Additional layers of the dialectic reflect different relationships between power
      and caring until they are seen as intertwined and mutually generative concepts in
      an approach to caring labeled "empowered caring".

PMID- 8865997
TI  - The ethics of compliance: a dialectic.
AB  - Compliance with prescribed therapeutic regimens is a construct that begs for
      consideration from an ethical perspective. This article offers a dialectical
      study of the nurse-client relationship, derived from Gadow's framework of ethical
      knowledge, that provides an alternative to compliance as context for nursing
      therapeutics. The dialectic move from compliance as thesis to isolated autonomy
      as antithesis is explored. Gadow's notion of engagement is elaborated on and
      offered as a synthesis that transcends the paternalistic and coercive assumptions
      underlying compliance and overcomes the dilemmas presented by the issues for
      power, consumerism, and beneficence that are inherent in isolated autonomy.

PMID- 8865998
TI  - Dirty hands: the underside of marketplace health care.
AB  - The ethos of the corporation and the urgency for profit maximization place
      pressures on health care corporations to act in a way that may be incompatible
      with ethical practice. Profit-driven incentives often result in corporate
      deviance and criminal behavior. Nurses may be pressured to go along with schemes
      that may be unethical or illegal and because of shaky job markets may be unable
      to adhere to professional ethical guidelines. Recent events in health care are
      drawn on to argue that ethical theory and research must begin to consider the
      issue of moral compromise of professionals as a result of deviant organizational
      environments.

PMID- 8865999
TI  - An occupational transmission of HIV: collision of ethical worlds in nursing
      practice.
AB  - This article proposes a new theoretical frame for ethical practice in nursing by
      locating ethical questions within the worlds of everyday nursing experience. The
      authors advocate a process of ethical thought and action that is not so much a
      weighing of dichotomized alternatives as a continual journey in which nurses
      delve deeper into their examination of clinical contexts, structural
      contingencies, and the meanings of experience for themselves and their clients.
      This theoretical vision is illustrated with a case study about a nurse who was
      infected with HIV on the job. The purposes in presenting the case study are to
      give testament to this brave woman's story, illustrate the dynamics of a
      contextualized ethics, and challenge nurses to make changes in practice, policy,
      and structure to foster truly ethical work and relations with others.

PMID- 8866000
TI  - Life support decisions for children: what do parents value?
AB  - This investigation answered the question, What meaning do parents give to the
      decision to authorize or to withdraw or forgo authorization of life-sustaining
      treatment for a child? Using an exploratory design, the author interviewed 20
      families who had faced this decision in the prior 6 to 12 months. From content
      analysis, parents' essential meaning was experienced through their sense of self,
      their being, and an ethic of responsibility. Parents' decisions reflected values
      regarding the eight key themes of life, pain and suffering, quality of life, not
      self, respect for person or best interest, family, faith and nature, and
      technology.

PMID- 8866001
TI  - Ethics in the neonatal intensive care unit: parental perceptions at four years
      postdischarge.
AB  - Ethical issues for the parents of neonates in neonatal intensive care units
      (NICUs) have not been widely researched. A multistage, qualitative project
      explored 23 families' perceptions of moral conflict and ethical decision making
      related to the NICU experience. Through in-depth interviews and the use of
      content analysis at 4 years postdischarge, life goes on (the major theme) and
      three conceptual categories were identified as characterizations of this phase.
      This phase, combined with two earlier phases (predischarge and 6 months
      postdischarge), represents a clinical manifestation of Reich's Theory of
      Suffering and provides a framework for understanding the parents' ethical
      perspective. Strategies for nurses that will facilitate parental participation in
      ethical decision making are presented.

PMID- 8866002
TI  - Fatty acid composition and chilling resistance in the green alga Caulerpa
      prolifera (Forrskal) Lamouroux (Chlorophyta, Caulerpales).
AB  - Plant resistance to chilling injury depends on the maintenance of membrane
      functions. An increase in the degree of unsaturation of membrane fatty acids can
      help maintain membrane function at low temperatures by reducing the temperature
      at which deleterious membrane phase-transitions occur. The fatty acid composition
      of membranes of the chlorophycean Caulerpa prolifera was determined in summer and
      winter in the Mar Menor coastal Lagoon (SE Spain). In January the percentage of
      polyunsaturated fatty acids was higher than in August. Membrane content of mono-
      and diunsaturated fatty acids was similar in the two seasons. The unsaturation
      index of membranes changed from 76.15 +/- 1.80 (mean +/- standard error) in
      August to 128.05 +/- 0.32 in January. It is suggested that this increase in the
      degree of unsaturation might be important to allow C. prolifera to decrease its
      lower threshold of survival temperature and acclimate net photosynthesis and dark
      respiration rates to winter temperatures in the Mar Menor.

PMID- 8866003
TI  - Okadaic acid increases fibronectin synthesis in MC3T3-E1 cells.
AB  - Okadaic acid, a potent specific inhibitor of serine/threonine protein
      phosphatases type 1 and 2A, affects several gene expressions in various cells. To
      determine whether okadaic acid affects the expression of fibronectin in MC3T3-E1
      cells, we measured mRNA level and synthesis of fibronectin by Northern blot
      hybridization and immunoprecipitation methods, respectively. Okadaic acid (10-50
      ng/ml) increased both mRNA level and synthesis of fibronectin in a dose-dependent
      manner. The increase of fibronectin mRNA by okadaic acid was strongly attenuated
      by the inhibition of new protein synthesis. The results indicate that okadaic
      acid, inhibitor of protein phosphatases, increases fibronectin synthesis in MC3T3
      E1 cells.

PMID- 8866004
TI  - Expression of jumper ant (Myrmecia pilosula) venom allergens: post-translational
      processing of allergen gene products.
AB  - N-terminal analyses of electrophoretically-separated allergenic polypeptides of
      the venom of the jumper ant M. pilosula showed that five out of the six
      allergenic polypeptides identified are homologous with the cloned major allergen
      Myr p I and may be derived from a single precursor polypeptide. The sixth
      polypeptide is homologous with a second cloned major allergen, Myr p II which is
      expressed as a single precursor polypeptide but exists in its native form as a
      disulphide bond-linked complex.

PMID- 8866005
TI  - Interactions of trans-acting factor(s) with the estradiol response element and
      nuclear factor 1 of the vitellogenin II gene of Japanese quail.
AB  - This study was directed at achieving an understanding of the mechanisms by which
      steroid hormones control the synthesis of vitellogenin (VTG) protein in the liver
      of the Japanese quail. Northern hybridization shows that administration of
      estradiol alone or with progesterone stimulates the synthesis of VTG mRNA. Gel
      mobility shift assay of DNA fragments containing the ERE and NF 1 shows that
      estradiol alone or with progesterone increases the levels of nuclear proteins
      that bind to these cis-acting elements of the promoter of the VTG gene. The
      cooperative effect of the two hormones seen at the level of expression of the VTG
      gene may be due to protein-protein interactions of trans-acting factors that bind
      to ERE and NF 1.

PMID- 8866006
TI  - Stimulation of fibronectin synthesis through the protein kinase C signalling
      pathway in normal and transformed human lung fibroblasts.
AB  - We examined the role of the protein kinase C (PKC) signaling pathway in the
      stimulation of fibronectin synthesis in both normal and transformed human lung
      fibroblasts. Phorbol myristate acetate (PMA), a potent PKC activator, stimulated
      fibronectin synthesis in both normal and transformed fibroblasts in a time and
      dose dependent fashion. Down-regulation of PKC by prior exposure of cells to a
      high concentration of PMA blocked the increase in fibronectin synthesis and mRNA
      levels induced by PMA. Bisindolylmaleimide, a specific inhibitor of PKC, also
      abolished the PMA-induced fibronectin synthesis. 4 alpha-phorbol didecanoate, an
      inactive phorbol ester, failed to affect fibronectin synthesis. These data
      suggest that PMA stimulates fibronectin synthesis and gene expression through the
      PKC signaling pathway in both normal and transformed human lung fibroblasts.

PMID- 8866008
TI  - Investigation of the effect of tetrahydroaminoacridine on turnover kinetics of
      camel (Camelus dromedarius) retina acetylcholinesterase.
AB  - The effect of tetrahydroaminoacridine (THA) on turnover kinetics of camel retina
      acetylcholinesterase has been investigated. The turnover number (Kcat) and
      specificity constant (Ksp) were 62.1 min-1 and 9.92 x 10(5) (M. min)-1 in the
      control system while the values for both parameters were lowered by 25-68% and 48
      87% in the THA (0.05-0.4 microM) treated systems respectively. Therefore, THA's
      effect on turnover number must be considered at the time of therapy to the
      Alzheimer's disease patients.

PMID- 8866007
TI  - ATP-diphosphophydrolase activity in rat heart tissue.
AB  - Extracellular nucleotides interact with specific receptors on the cell surface
      and are locally metabolized by ecto-nucleotidases. Biochemical characterization
      of the ATPase and ADPase activities detected in rat heart sarcolemma, under
      conditions where mitochondrial ATPase and adenylate kinase were blocked, supports
      our proposal that both activities correspond to a single enzyme, known as ATP
      diphosphohydrolase or apyrase. The physiological function of this enzyme could be
      dephosphorylation of the nucleotides present in the interstitial heart
      compartment acting together with 5'-nucleotidase. Both hydrolytic activities have
      similarities in: sarcolemma localization, bivalent metal ion dependence, optimum
      pH, effect of several amino acid residue modifiers, competitive inhibition of
      nucleotide analogs, and broad nucleoside di-and triphosphate specificity. The
      ATPase activity could not be separated from the ADPase either through
      isoelectrofocusing or electrophoresis under acid conditions.

PMID- 8866009
TI  - Inhibition studies of the carnitine acetyltransferase from skeletal muscle of the
      camel (Camelus dromedarius) by sulfhydryl reagents and metal ions.
AB  - The effect of certain sulfhydryl reagents and metal ions were studied on the
      carnitine acetyltransferase (CAT) activity from the skeletal muscle of the
      Arabian camel (Camelus dromedarius). DTNB and iodoacetamide caused concentration
      and time dependent inhibition of CAT activity. The inhibition seen with these
      sulfhydryl reagents could be protected with prior incubation of the enzyme with
      acetyl-Co A, suggesting that these reagents might interact with the same site.
      Among the various metal ions tested, Cu2+, Zn2+ and Hg2+ caused total inhibition
      at very low concentrations, while, Mn2+, Mo6+ and Co2+ caused between 32-52%
      inhibition at 10 mM concentrations. Alkali earth divalent metals Mg2+ and Ca2+
      caused less than 15% inhibition at this concentration. These metal ions are
      probably interacting at certain nucleophilic groups in the enzyme thus disrupting
      its tertiary structure.

PMID- 8866010
TI  - Estrogen surge: a regulatory switch for superoxide radical generation at
      implantation.
AB  - This study is undertaken to identify the regulatory switch for the activation of
      superoxide radical generation pathway and repression of superoxide dismutase
      (SOD) at the time of implantation using estrogen as a control factor and delayed
      implantation as a model system. The results revealed high SOD activity and
      negligible oxyradical generation in progesterone-treated animals on day-5 and day
      8 (delayed implantation) while an enormous rise in oxyradical generation and an
      abrupt fall in SOD in animals which received both estrogen and progesterone
      injections were observed on days 5 and 8 of pregnancy. These results strongly
      suggest that estrogen regulates superoxide anion radical generation by lowering
      the SOD activity.

PMID- 8866011
TI  - Redox modifications of spinach chloroplast fructose-1, 6-bisphosphatase.
AB  - Complete activation of chloroplast fructose-1, 6-bisphosphatase by dithiothreitol
      involves the reduction of its four disulfide bonds as revealed by thiol titration
      and activity measurement. Both before and after reduction, the enzyme is
      inhibited by the thiol-specific reagent 5,5'-dithiobis(2-nitro-benzoic acid) with
      complete inactivation upon modifications of the four accessible thiols. However,
      oxidative modification of the enzyme facillitates the reduction of the four
      mentioned disulfide bonds as the process of activation by DTT is accelerated.

PMID- 8866012
TI  - Butachlor impact on protein, free amino acid and glutamine contents, and on
      activity levels of aminotransferases, glutamate dehydrogenase and glutamine
      synthetase in the fresh water snail, Pila globosa (Swainson).
AB  - Biochemical changes followed in the freshwater snail Pila globosa (Swainson)
      during exposure to sublethal concentrations of the herbicide butachlor (26.6 ppm)
      in the ambient medium, at 3,6,12,24 and 48 h intervals, were marked by a
      significant decrease in total and soluble proteins, and an increase in free amino
      acids in foot and hepatopancreas up to 12 h before gradually recovering.
      Aminotransferase activities and glutamine content decreased during the early
      periods of exposure, while glutamate dehydrogenase activity increased. After an
      initial elevation, glutamate synthetase activity decreased at later intervals.
      Maximum effect of butachlor on the enzymes was seen after 12 h exposure. The
      extent of increase or decrease in different parameters examined varied between
      the two tissues studied. These changes are discussed in relation to the toxic
      stress of butachlor.

PMID- 8866013
TI  - Subunit structure of Ca++ dependent soluble goat hepatic lectin: evidence that it
      has antigenic structural relationship with soluble 14K lectin family.
AB  - The subunit structure of soluble goat hepatic lectin was studied by determining
      molecular weight under nondenaturing conditions by gel filtration and denaturing
      conditions by SDS PAGE. Affinity purified lectin was subjected to HPLC on
      asahipack column equilibrated with 10 mM Tris-HCl pH 7.5, containing 1 mM CaCl2,
      1mM 2-mercaptoethanol and 0.1M NaCl. The lectin was eluted under single peak at
      retention time of 12 min. corresponding to molecular weight of 38Kd. On SDS-PAGE
      in the presence and absence of 2-mercaptoethanol protein moved as single band
      with Rm 0.45, which corresponds to molecular weight of 20 Kd. The results suggest
      that soluble goat hepatic lectin is a dimmer of identical subunits which are
      linked together by noncovalent interactions. The interaction of monoclonal
      antibodies raised against soluble goat hepatic lectin (MGHL/20) with
      hemagglutinin from different species as sheep, human, rat, bovine and chicken was
      studied in PBS by solid phase binding assay. MGHL/20 showed 29.89% binding with
      these lectin. However no binding was found with Ca++ dependent membrane bound
      lectin. These results indicate that soluble goat hepatic lectin possesses
      antigenic structural relationship with soluble 14 K lectin family.

PMID- 8866015
TI  - Intravenous injections of the ribosome inactivating protein trichosanthin did not
      affect methionine enkephalin and beta-endorphin levels in the mouse brain and
      pituitary.
AB  - The effect of trichosanthin on levels of the neuropeptides beta-endorphin (beta
      EP) and methionine enkephalin (met-EK) in the mouse brain and pituitary was
      investigated. Mature male ICR mice were divided into two groups. One group
      received intravenous injections of physiological saline and served as the
      control. Another group received daily intravenous injections of trichosanthin
      (0.2 mg/25g/injection) for three consecutive days. The animals were sacrificed
      four hours after the last injection. Their brains were dissected into three
      regions: A (thalamus and hypothalamus), B (cerebral cortex) and C (cerebellum and
      brainstem) and their pituitaries were collected. The samples were then extracted
      and assayed for beta-EP and met-EK by specific radioimmunoassays. It was found
      that there were no statistically significant changes in the levels of the two
      neuropeptides in the pituitary and the brain regions except for the level of beta
      EP in brain region A.

PMID- 8866014
TI  - A comparison of epidermal growth factor receptor-mediated mitogenic signaling in
      response to transforming growth factor alpha and epidermal growth factor in
      cultured fetal rat hepatocytes.
AB  - We compared the ability of Epidermal Growth Factor (EGF) and Transforming Growth
      Factor alpha (TGF alpha) to transduce a mitogenic signal via their common
      receptor, the EGF receptor, in primary cultures of fetal rat hepatocytes.
      Mitogenic potency, measured as DNA synthesis, was similar in response to EGF and
      TGF alpha although signal initiation, measured as EGF receptor tyrosine
      phosphorylation, was more than 3-fold higher in response to EGF compared to TGF
      alpha. Downstream signal transduction events including Shc tyrosine
      phosphorylation, Shc/Grb2 complex formation and MAP kinase activation were
      similar in response to EGF and TGF alpha, thus indicating a dissociation between
      potency for receptor activation versus signal propagation. These data suggest
      that TGF alpha may preferentially activate an EGF receptor population linked to
      the Ras/MAP kinase pathway. In contrast, EGF shows no such selectivity, thereby
      reducing the mitogenic potency of EGF relative to its ability to activate the EGF
      receptor.

PMID- 8866016
TI  - Regulation of the activity of M-phase promoting factor through protein kinase A
      mediated pathway in LP1-1 cells.
AB  - Treatment of cAMP analogs, dibutyryl cAMP and 8-bromo-cAMP, was found to inhibit
      the proliferation of mouse fibroblast LP1-1 cells and the p34cdc2 kinase activity
      of M-phase promoting factor (MPF). However, it showed relatively little effect on
      expression of the cyclin B1 and cdc2 genes. On the other hand, when the nuclear
      extracts obtained from the cells at early G2 phase were treated with cAMP
      analogs, the kinase activity was significantly decreased as compared to the
      untreated control. Furthermore, the inhibitory effect of cAMP analogs could be
      reversed upon treating with okadaic acid even in the presence of the cAMP
      analogs, implying that cdc25 remains in an active form. In addition, the
      treatment of okadaic acid stimulated the cell progression. These results suggest
      that down-regulation of MPF activity through protein kinase A-mediated pathway is
      under post-translational control and cdc25 activation pathway involving okadaic
      acid-sensitive phosphatase play a role in the regulation of MPF activity.

PMID- 8866017
TI  - Zearalenone-induced uncoupling in plant mitochondria is sensitive to 6
      ketocholestanol.
AB  - Zearalenone (F-2) is a mycotoxin which acts as a protonophoric uncoupler in plant
      mitochondria [Macri, F. and Vianello, A., (1990) J. Plant Physiol. 136, 754-757].
      In the present paper, the mechanism of F-2-induced uncoupling in pea mitochondria
      was studied. The uncoupling by F-2 was partially reversed by 6-ketocholestanol
      (kCh) under conditions in which kCh completely reversed the FCCP-induced
      uncoupling and almost did not affect the palmitate-induced uncoupling. Recoupling
      effects of carboxyatractylate, ADP and cyclosporin A were small and could not
      essentially decrease the kCh-insensitive part of F-2-induced uncoupling. It is
      suggested that a protein, mediating kCh-sensitive uncoupling, is involved in the
      F-2 effect in plant mitochondria.

PMID- 8866019
TI  - Properties of 26S proteasome purified from rat skeletal muscles: comparison with
      those of 26S proteasome from the rat brain.
AB  - A ubiquitin/ATP-dependent proteolytic complex (26S proteasome) was highly
      purified from rat skeletal muscles and its enzymatic properties were compared
      with those of the brain 26S proteasome. The purified 26S proteasome comprises 22
      110 kDa subunits characteristic of the typical 26S proteasome on the basis of SDS
      PAGE. The two-dimensional PAGE (NEPHGE and SDS-PAGE) pattern revealed that the pI
      values and molecular masses of the muscle 26S proteasome subunits were similar
      but not identical to those of the subunits of 26S proteasome purified from the
      rat brain. The enzymatic properties of the muscle 26S proteasome were very
      similar to those of the brain enzyme in substrate specificity and inhibitor
      susceptibility. The specific activities of the muscle 26S proteasome toward three
      fluorogenic peptide substrates were indistinguishable from those of the brain
      enzyme.

PMID- 8866018
TI  - Yeast thiol-dependent protector protein expression enhances the resistance of
      Escherichia coli to hydrogen peroxide.
AB  - A soluble protein from Saccharomyces cerevisiae specifically provides protection
      against a thiol-containing oxidation system but not against an oxidation system
      without thiol. This 25-kDa protein was thus named thiol-dependent protector
      protein (TPP). The role of TPP in the cellular defense against oxidative stress
      was investigated in Escherichia coli containing an expression vector with a yeast
      genomic DNA fragment that encodes TPP (strain YP) and mutants in which the
      catalytically essential amino acid cysteine (Cys-47) has been replaced with
      alanine (strain YPC47A) or tryptophan (Trp-82) has been replaced with
      phenylalanine (strain YPW82F) by a site directed mutagenesis. There was a
      distinct difference between these three strains in regards to growth inhibition
      kinetics, viability, modulation of activities of superoxide dismutase and
      catalase, and the accumulation of oxidized proteins. These results suggest that
      TPP may play a direct role in the cellular defense against oxidative stress by
      functioning as an antioxidant protein.

PMID- 8866020
TI  - Cystatin-like domain of mouse countertrypin, a member of mammalian fetuin family,
      is responsible for the inhibition of trypsin. Evidence from site-directed
      mutagenesis.
AB  - Members of mammalian fetuin family, such as human alpha 2 HS glycoprotein and
      bovine fetuin, consist of three domains, two tandemly arranged cystatin-like
      domains and an unrelated domain, but they have no inhibitory activity against
      cysteine proteinases. We found that countertrypin, a novel trypsin inhibitor, is
      mouse counterpart of human alpha 2 HS glycoprotein, and that human alpha 2 HS
      glycoprotein and bovine fetuin which were prepared without use of ethanol are
      capable of inhibiting trypsin (Yamamoto, K. and Sinohara, H. (1993) J. Biol.
      Chem, 268, 17750-17753). In the present study, cDNA encoding countertrypin was
      isolated and sequenced, and evidence is presented, based on the site-directed
      mutagenesis, that lysine-231 in the second cystatin domain is the P1 site for
      trypsin inhibition.

PMID- 8866022
TI  - Studies on the lipid metabolism of Walker 256 tumour-bearing rats during the
      development of cancer cachexia.
AB  - Aspects of the lipid metabolism of Walker 256 carcinosarcoma-bearing cachectic
      rats (TB) were investigated during a 14 day interval of tumour growth. Food
      intake and body weight of the TB rats were reduced by 18% and 13%, respectively,
      on day 14, as compared with non-tumour-bearing animals. The tumour burden then,
      corresponded to 19% of total body weight. The total fat content was not different
      in the liver, heart, carcass, epididymal (EAT) and retroperitoneal (RPAT) adipose
      tissues of the two groups. The brown adipose tissue (BAT) and skeletal muscle
      (gastrocnemius-SM) of the TB rats had increased levels of fat (23% and 200%,
      respectively). Enteral absorption of 14C-triolein was decreased in the TB rats,
      but the liver, heart, and SM of these animals incorporated more radiolabelled
      lipid than the control animals, while the adipose tissues exhibited a decreased
      incorporation of radioactivity in relation to controls. More lipid was
      incorporated into the VLDL fraction secreted by the liver of TB rats, which
      exhibited a different distribution of the incorporated 14C-oleate in the various
      lipid subfractions. Ultrastructural studies showed that the hepatocytes of the TB
      rats had a greater incidence of lipid droplets in the cytoplasm.

PMID- 8866021
TI  - Elevated catalase activity in red and white muscles of MyoD gene-inactivated
      mice.
AB  - MyoD is a myogenic transcription factor responsible for skeletal muscle
      differentiation during development. Muscle antioxidant enzyme status was
      determined in transgenic MyoD deactivated mice. While catalase activity was
      significantly (P < 0.05) elevated in soleus and extensor digitorum longus muscles
      from MyoD deactivated mice, superoxide dismutase and glutathione peroxidase
      activities were not. While this may imply a greater propensity for inherent
      oxidative stress, soleus glutathione status was similar between MyoD deactivated
      mouse and control soleus muscles. Catalase activity is localized primarily in
      peroxisomes. Therefore elevated catalase activity may also indicate the presence
      of factors associated with peroxisome proliferation in muscles from MyoD gene
      inactivated mice.

PMID- 8866023
TI  - Organization of the XYL genes in a thermophilic Bacillus species.
AB  - The organization of the genes involved in xylose catabolism in a thermophilic
      Bacillus sp. LW2 was found to be different from that of mesophiles such as B.
      subtilis and Escherichia coli. We have reported previously the cloning and
      characterization of the xylose isomerase gene (xylA) from this thermophilic
      Bacillus sp. A xylose transport permease gene (xylP) was located immediately
      upstream of xylA. This gene encoded a hydrophobic protein (392 amino acids) with
      a calculated molecular weight of 42,307. Further upstream of xylP, another
      related gene xylO encoding a sugar transport ATP-binding protein was observed. A
      xylulose kinase gene (xylB) was identified downstream of xylA. Its open reading
      frame extended up to 1122 bp and represented a part (372 aa) of the enzyme. The
      order of the xyl genes in the thermophilic Bacillus sp. is therefore 5'-xylO (ATP
      binding protein)-xylP (xylose permease)-xylA (xylose isomerase)-xylB (xylulose
      kinase)-3'. The polarity of expression of these four genes was found to be
      unidirectional from xylO to xylB.

PMID- 8866024
TI  - Immunochemical studies on human, bovine and pig brain regulatory subunits of cAMP
      dependent protein kinase type II.
AB  - Regulatory subunits type II (RII) purified from human, pig and bovine brains were
      compared using II monoclonal antibodies (MoAb) against bovine brain RII. Bovine
      RII has at least 5 antigenic sites located in the N-terminal 1-110 residues.
      Immunochemical difference detected between human and animal RII was more
      pronounced than between pig and bovine RII. Certain MoAb influenced R-cAMP
      binding and holoenzyme formation. RII of the three species responded to MoAb
      attachment in a similar fashion. The results suggest that anchoring of neural
      protein kinase via the N-terminal part of RII may influence the enzyme activity.

PMID- 8866025
TI  - GM-CSF induces the tyrosine phosphorylation of three isoforms of Shc and its
      association with Grb2 in TF-1 cell.
AB  - This report demonstrates that GM-CSF induces the tyrosine phosphorylation of Shc
      protein which is implicated in Ras activation. Three isoforms of Shc are
      ubiquitously phosphorylated induced by GM-CSF in TF-1, a cell line of erythroid
      origin. It is also shown that Shc is associated with the adaptor protein Grb2.
      The formation of Shc-Grb2 complex may directly link tyrosine phosphorylation
      events to Ras activation in TF-1 cells.

PMID- 8866026
TI  - Mechanical properties of hydrogels and their experimental determination.

PMID- 8866027
TI  - Biological molecule-impregnated polyester: an in vivo angiogenesis study.
AB  - Specific extracellular matrix molecules and growth factors (GFs) with angiogenic
      properties could be combined with biomaterials to enhance angiogenesis and
      subsequently tissue ingrowth through the wall of the porous structure. In this
      study, composite fibrin matrices containing hyaluronic acid (HA), fibronectin
      (FN) and/or fibroblast growth factor-1 (FGF-1), FGF-2 and an endothelial cell
      growth supplement (ECGS) were adsorbed onto Dacron meshes which were then
      implanted subcutaneously in mice. The release from the implants and the tissue
      distribution of implanted GFs were determined in vivo using radiolabelled FGF-2.
      Angiogenesis was quantified by counting the number of capillaries present in each
      Dacron histological serial section. Radiolabelled GF was rapidly released from
      matrices and was absent from them by day 28. A very low percentage of the
      implanted radiolabelled GFs was found in the kidneys and livers of the animals.
      The number of microvessels formed within fibrin-impregnated samples was increased
      in the presence of HA and ECGS at 14 d and of FN and ECGS or FGF-2 at 28 d. FGF-1
      had no direct effect on angiogenesis in our model. These results indicate that
      enhancement of vascularization within prosthesis mesh may be achieved by using
      fibrin as a support for angiogenic molecules such as HA, FN and FGFs.

PMID- 8866028
TI  - Kinetics of anhydride formation in xerogels of poly(acrylic acid).
AB  - The aim of this work was to study the cross-linkage of xerogels made of Carbopol
      of different molecular weight (polymers deriving from polyacrylic acid), and the
      influence exerted by different percentages of beta-cyclodextrin upon the cross
      linkage percentage. Xerogels were obtained by high-pressure compression and cross
      linking was studied by measuring the weight loss of different formulations over a
      temperature range of 70 to 190 degrees C. Kinetics of anhydride formation were
      found to follow a second-order mechanism with an activation energy of
      approximately 25 kcal mol-1.

PMID- 8866029
TI  - Elastic behaviour of sutured calf pericardium: influence of the suture threads.
AB  - The purpose of this study was to assess the elastic behaviour of calf pericardium
      used in the construction of cardiac bioprosthesis valve leaflets, sutured with
      different types of commercially available sutures: silk, Gore-Tex, Surgilene and
      nylon. Thirty-two samples (four series of eight samples each) were subjected to
      tensile strength testing to breakage. The breaking stress (MPa) ranged between
      4.89 MPa for samples sutured with Gore-Tex and 5.22 MPa for those sewn with
      nylon. Three samples from each series were subjected to a stepwise stress test,
      involving increasing levels of stress followed by return to zero, to define the
      elastic limit (the cut-off point beyond which strain is no longer reversible).
      Analysis of the results provided the mathematical functions that govern the
      elastic behaviour (stress/strain) within the elastic range for each type of
      sutured sample. The series sutured with Surgilene presented the highest mean
      value (1.649 MPa). Finally, a statistical study was carried out to determine
      which series showed the greatest probability of having the least interaction
      between the thread and the pericardium. Allowing an interval of +/- 10%, Gore-Tex
      showed the best probability in this respect. However, real fatigue testing is
      necessary to definitively determine which is the best suture to use.

PMID- 8866030
TI  - Meniscal repair by fibrocartilage in the dog: characterization of the repair
      tissue and the role of vascularity.
AB  - Lesions in the avascular part of 20 canine menisci were repaired by implantation
      of a porous polyurethane. Seven menisci were not repaired and served as controls.
      The repair tissue was characterized by biochemical and immunological analysis.
      The role of vascularity in healing was studied by perfusion of menisci with
      Indian ink. Histologically, repair tissue inside the implants initially consisted
      of fibrous tissue containing type I collagen. After 2 months, fibrocartilaginous
      tissue developed inside the implants, whereas control defects only showed repair
      with fibrous tissue. Both type I and type II collagen, the two major collagen
      types of normal meniscal fibrocartilage, could be detected in this newly formed
      fibrocartilage. The implant guided vascular tissue from the periphery towards the
      lesion resulting in healing of the tear. After fibrocartilage had formed,
      vascularity decreased and was completely absent in mature fibrocartilage. Control
      defects remained filled with vascular connective tissue. Two-thirds of the
      longitudinal lesions were found to be healed partially or completely. It is
      concluded that implantation of a porous polymer does enhance vascularity
      sufficiently to result in healing of meniscal lesions extending into the
      avascular part. Healing takes place by repair tissue strongly resembling normal
      meniscal fibrocartilage.

PMID- 8866031
TI  - Evaluation of an epoxy-fixed biological patch with ionically bound heparin as a
      pericardial substitute.
AB  - In an attempt to develop an improved pericardial substitute, we undertook the
      development of an epoxy-fixed biological patch with ionically bound heparin. The
      study was to evaluate the cross-linking characteristics of this newly developed
      biological patch using its glutaraldehyde-fixed counterpart as a control. In
      addition, the feasibility of using this newly developed biological patch as a
      pericardial substitute was assessed in a canine model. In the study, it was
      observed that the epoxy-fixed biological patch appeared more similar to the
      native pericardium in colour and was more pliable than its glutaraldehyde-fixed
      counterpart. Also, both the epoxy- and glutaraldehyde-fixed biological patches
      had significant increases in fixation index and denaturation temperature as
      compared to the fresh one (p < 0.05). In the canine study, the epoxy-fixed
      biological patch with ionically bound heparin was found to have significantly
      less adhesion formation than those currently used clinically (p < 0.05).

PMID- 8866032
TI  - In vitro assessment of phagocytosis of bovine collagen by human
      monocytes/macrophages using a spectrophotometric method.
AB  - The use of a wound dressing with covering and haemostatic properties
      significantly improves wound healing. In this study, a lyophilized bovine
      collagen sponge used for the treatment of wounds and ulcerae has been tested in a
      cell culture system. Phagocytosis of collagen fragments by human blood
      monocytes/macrophages has been investigated. For the assessment of collagen
      ingestion by mononuclear phagocytes, a picrosirius dye specific for collagen
      molecules has been used. By adapting this histochemical technique to microplate
      cell culture system, replicate monocyte cultures are assayed. Collagen content is
      determined by evaluating spectrophotometrically at 540 nm the absorbance of a
      sirius red/picric acid solution. Using this simple and sensitive method, the
      phagocytosis of bovine collagen by LPS-stimulated monocytes/macrophages has been
      ascertained.

PMID- 8866033
TI  - Development of hydroxyapatite derived from Indian coral.
AB  - A simple method of converting the calcium carbonate skeleton of the corals
      available in the Indian coast into hydroxyapatite granules has been developed. By
      heating the coral to 900 degrees C, the organic materials were eliminated. Powder
      X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR)
      and thermogravimetric analysis (TGA) were employed to characterize the coral and
      to optimize the processing parameters as well as to confirm the hydroxyapatite
      formation. The coral used exhibits the presence of both aragonite and calcite
      phases (dimorphism). At a temperature of 900 degrees C the coral was found to
      decompose all the carbonate phases. The pre-heated coral is converted into
      hydroxyapatite by a chemical exchange reaction with di-ammonium phosphate under
      hydrothermal conditions. The hydroxyapatite obtained was in powder form and does
      not contain any impurities. The in vitro solubility test of the apatite granules
      performed in Gomoris, Michalelis, Sorensens, Ringer's and phosphate buffer of pH
      7.2 and de-ionized water indicated the stability of the coralline hydroxyapatite.

PMID- 8866034
TI  - Processing and mechanical properties of hydroxyapatite reinforced with
      hydroxyapatite whiskers.
AB  - Hydrothermally synthesized HAp fine crystals/HAp whiskers mixtures have been used
      for the preparation of HAp/0-30% (whiskers) composites. The composites have been
      fabricated by pressureless sintering and hot-pressing. The best mechanical
      properties and the highest densities have been achieved for composites hot
      pressed at 1000 degrees C (2 h, 30 MPa in flowing Ar). Their density was in the
      range of 90-97% of the theoretical density. Fracture toughness (Klc) of the
      composites reflected their microstructure and had the value of 1.4 MPa m1/2 (as
      compared with Klc = 1.0 MPa m1/2 for the non-reinforced HAp matrix). Compressive
      prestressing of the HAp matrix and crack deflection (both derived from the
      residual stress field) contributed to the increase of fracture toughness. Other
      toughening mechanisms have not been observed. HAp/HAp (whiskers) composites
      exhibited improved toughness without degradation of biocompatibility, because the
      HAp whiskers acted both as a reinforcement and as a biocompatible phase. Problems
      related to biocompatibility and mechanical properties of available HAp-based
      composites were also discussed.

PMID- 8866035
TI  - Bone formation inside the material interstices of e-PTFE membranes: a light
      microscopical and histochemical study in man.
AB  - Membranes used in guided bone regeneration (GBR) should possibly achieve a good
      degree of tissue integration with neighbouring connective tissues in order to
      obtain a mechanically stable environment necessary for successful bone and soft
      tissue healing. The authors observed, in a histological study of e-PTFE membranes
      used for GBR and retrieved from 10 patients, inside the material interstices of
      the membranes, in many cases the presence of connective tissue cells and collagen
      fibres, and in two cases the presence of bone. The presence, inside the membrane,
      of connective tissue and bone could help toward a tight integration between the
      membrane and neighbouring tissues, with the production of a biological seal.

PMID- 8866036
TI  - Comparative investigation of drug delivery of collagen implants saturated in
      antibiotic solutions and a sponge containing gentamicin.
AB  - Collagen implants of various structures and a gelatine sponge were placed in five
      different antibiotic solutions until complete saturation occurred. The
      antibiotics were chosen to represent different drug classes (gentamicin sulphate,
      cefotaxim, fusidic acid, clindamycin, vancomycin). The collagen implants
      saturated with antibiotic solution and a lyophilized collagen sponge containing
      gentamicin sulphate were eluated in 0.066 M phosphate buffer (pH = 7.4) at 37
      degrees C. The total eluation period is 7 d with buffer changes every 24 h. The
      antibiotic delivery by the collagen implants and the lyophilized sponge
      containing gentamicin sulphate is complete after a maximum of 4 d. If an implant
      that has a protective effect against wound infections over a period of 24-48 h is
      required, the materials described here are suitable. However, where treatment in
      infected areas should ensure antibiotic cover for 5-10 d, neither collagen
      materials immersed in antibiotic solutions nor collagen sponges containing
      gentamicin are suitable.

PMID- 8866037
TI  - Characterization of a 7 day 17 beta-estradiol transdermal delivery system:
      pharmacokinetics in healthy postmenopausal women.
AB  - To assess the delivery characteristics of a new 7 day 17 beta-estradiol
      transdermal delivery system (TDS), estradiol and estrone pharmacokinetics were
      evaluated following a single 7 d application of one TDS or two TDSs in 24
      healthy, postmenopausal women in a nonblind, randomized, two-period crossover
      study. Serial blood samples and total urine output were collected before
      (baseline measurement of endogenous hormone) and during TDS application, and for
      24 h (urine) or 72 h (blood) following TDS removal. Serum was assayed for
      estradiol and estrone by a validated radioimmunoassay (RIA) method. The combined
      amounts of estradiol and its conjugates, and estrone and its conjugates in urine
      were determined by validated RIA methods. Overall, one or two estradiol TDSs were
      well tolerated by healthy, postmenopausal female volunteers. Estradiol absorption
      from the TDS was characterized by a zero-order process and was dose proportional,
      resulting in average steady-state serum estradiol concentrations of 16 and 33 pg
      mL-1 above baseline during the 7 d application of one and two TDSs, respectively.
      Parallel but smaller increases in serum estrone concentrations were observed,
      resulting in an increase in the serum estradiol/estrone concentration ratio from
      approximately 0.2 at baseline to median values of 0.64 and 0.88 during
      application of one and two TDSs, respectively. The 7 day 17 beta-estradiol TDS
      delivered a nominal estradiol dose of 0.02 mg/24 h during the intended wear
      period.

PMID- 8866038
TI  - Bioequivalence of two orally administered nicardipine products.
AB  - The relative bioavailabilities of orally administered nicardipine (Zenith
      Laboratories) and nicardipine (Cardene Syntex Laboratories) were compared
      following a single 30 mg dose under fasted conditions using a two-way crossover
      study with 34 healthy adult male subjects. In a separate study the effect of food
      on the relative bioavailabilities of these products was assessed following an
      identical dose by comparing the Zenith product under fasted conditions, the
      Zenith product under fed conditions, and the Syntex product under fed conditions
      using a three-way crossover study with 17 healthy adult male subjects. In the
      fasted study, 90% confidence intervals surrounding ratios (Zenith/Syntex) of
      least-squares means derived from 1n-transformed data were 0.84-1.02 for AUCt,
      0.85-1.04 for AUCinfinity, and 0.86-1.05 for Cmax, clearly demonstrating
      bioequivalence of the two products. In the food-effect study ratios of least
      squares means (Zenith under fed conditions/Zenith under fasted conditions) were
      0.62 for AUCt, 0.65 for AUCinfinity, and 0.40 for Cmax, with tmax delayed from
      0.906 +/- 0.337 h (Zenith under fasted conditions) to 2.33 +/- 0.717 h (Zenith
      under fed conditions) and 2.84 +/- 0.834 h (Syntex under fed conditions).
      Findings indicate that the presence of food in the gastrointestinal tract reduces
      the bioavailability of orally administered nicardipine. However, ratios under fed
      conditions (Zenith/Syntex) were very close to unity for each metric, suggesting
      that the observed food effect is independent of the product formulation. Findings
      further suggested that food effects on conventional pharmacokinetic metrics might
      be attributed to alteration of extent, rather than rate, of gastrointestinal
      absorption. Finally, these results question the applicability of the peak plasma
      concentration (Cmax) as an index of absorption rate in nicardipine studies.

PMID- 8866039
TI  - In vivo/in vitro correlations for four differently dissolving ketorolac tablets.
AB  - This study assesses whether in vitro immediate release ketorolac tablet
      dissolution profiles (utilizing the recently proposed USP dissolution test for
      ketorolac tablets) can be correlated with in vivo plasma pharmacokinetic
      parameters. Four batches of ketorolac tablets were utilized: a ketorolac tablet
      batch that demonstrated a rapid dissolution rate during USP in vitro dissolution
      testing, two tablet batches that were manufactured such that they dissolved at
      moderate rates, and a tablet batch that was manufactured such that it dissolved
      at a distinctly slow rate. The single-dose mean pharmacokinetic characteristics
      and relative bioavailability of the four different 10 mg ketorolac tromethamine
      tablets were evaluated in 12 healthy volunteers in a randomized study of Latin
      square design. The amount dissolved of the various tablets at 10, 20, and 30 min
      was in the order of fast-dissolving tablets > medium-1-dissolving tablets =
      medium-2-dissolving tablets > slow-dissolving tablets. In general, the profiles
      of the average plasma concentrations for ketorolac were similar for the fast- and
      the two medium-dissolving tablet batches (even though a statistically significant
      difference was found between the tmax of the fast-dissolving tablet and one of
      the medium-dissolving tablet batches). The mean plasma concentrations for the
      slow-dissolving tablet, however, reached peak levels much later, with the peak
      also being significantly smaller. There were no statistically significant
      differences in the total AUC or in the mean plasma half-lives among the four
      formulations. Good correlations were obtained for mean tmax versus the percentage
      dissolved at 20, 30, and 45 min. Correlations were generally weaker for
      percentage dissolved versus Cmax or percentage bioavailability. This indicates
      that in vitro dissolution testing for immediate release ketorolac tablets can be
      a useful indicator of in vivo time to maximum plasma concentration when comparing
      similarly formulated tablets. Further, the proposed USP dissolution test and
      specification would have appropriately failed the slow-dissolving tablet batch,
      which demonstrated a significantly slower rate of absorption as per tmax and
      Cmax.

PMID- 8866040
TI  - A pharmacokinetic study with the high-dose anticancer agent menadione in rabbits.
AB  - The aim of this investigation was to assess the pharmacokinetic properties of
      high-dose menadione (VK3), as an anticancer agent, in plasma and red blood cells
      (RBCs) in rabbits. An extremely high dose of 75 mg menadiol sodium diphosphate
      (Synkayvite) was intravenously injected. HPLC analysis was applied to measure the
      major metabolite, menadione, VK3. The kinetic properties of VK3 in both plasma
      and red blood cells showed a short elimination half-life, high clearance, and
      large volume of distribution in plasma and RBCs. The mean elimination t1/2 values
      of menadione in plasma and in RBCs were 27.17 +/- 10.49 min and 35.22 +/- 11.82
      min, respectively. The plasma clearance (CL/F) of VK3 was 0.822 +/- 0.254 L min
      1. The systemic clearance in RBCs was 0.407 +/- 0.152 L min-1. The apparent
      volume of distribution (Vd/F) in plasma was 30.833 +/- 12.835 L and that in RBCs
      20.488 +/- 9.401 L. The plasma AUC was 32.453 +/- 9.785 micrograms min mL-1 and
      that of RBCs 67.219 +/- 24.449 micrograms min mL-1. Menadiol was rapidly
      biotransformed to menadione in blood. The formation rate constant (kf) of
      menadione in plasma was 0.589 +/- 0.246 min-1, and that of RBCs 1.520 +/- 1.345
      min-1. Through this study the estimated menadione dosage needed to maintain a
      plasma level of 1 microgram mL-1 for anticancer purposes was 19.7 mg kg-1 every
      hour.

PMID- 8866041
TI  - The thermal potentiation of acetaminophen-inhibited PMN oxidative metabolism in
      vitro.
AB  - The effect of high temperatures (39, 41, and 43 degrees C) on acetaminophen (AM-)
      induced inhibition of the oxidative respiratory burst of polymorphonuclear
      leukocytes (PMNs) in vitro has been examined. Whole blood or isolated human PMNs
      were exposed to various temperatures in vitro in the presence or absence of AM
      for 0-90 min. Phagocyte membrane-bound NADPH oxidase was studied using the
      luminol chemiluminescence (CL) response and the superoxide dismutase inhibitable
      reduction of ferricytochrome C. The NADPH oxidase was stimulated by phorbol
      myristate acetate (PMA). The results showed that high temperatures (39-43 degrees
      C) potentiate the AM inhibitory effect on CL peak response of phagocytes in a
      temperature-dependent manner. Furthermore, the inhibition of superoxide (O2-)
      production induced by AM was potentiated by incubating the cells at 39 or 43
      degrees C at different time intervals. These studies suggest that high
      temperatures significantly potentiate the AM inhibitory effect on oxidative
      metabolism of PMNs in vitro. These actions of AM may influence the outcome in
      patients with infectious febrile conditions.

PMID- 8866042
TI  - The effect of food on the bioavailability of ibuprofen and flurbiprofen from
      sustained release formulations.
AB  - The effect of food on the plasma concentration-time profile of sustained release
      dosage forms of ibuprofen and flurbiprofen has been investigated in healthy Asian
      Indian volunteers, in two separate studies. In study 1, 20 volunteers were
      administered a single 200 mg multiple-unit sustained release capsule of
      flurbiprofen (Froben SR), after an overnight fast or a heavy vegetarian
      breakfast. Food produced a statistically significant increase in the mean (+/-SE)
      maximal plasma concentration (Cmax) and area under the plasma concentration-time
      curve (AUC0-48). Cmax (+/-SE) increased from 9.88 +/- 0.48 mg L-1 (fasting) to
      11.36 +/- 0.88 mg L-1 (postprandial) and AUC0-48 (+/-SE) increased from 120.78 +/
      9.64 mg h L-1 (fasting) to 149.73 +/- 12.24 mg h L-1 (postprandial). The mean
      (+/-SE) time to peak (tmax) was also significantly delayed from 3.85 +/- 0.27 h
      to 8.70 +/- 0.89 h. In study 2, 18 volunteers were administered a single 800 mg
      erodible sustained release matrix tablet of ibuprofen (Brufen Retard), after an
      overnight fast or along with a heavy vegetarian breakfast. The formulation
      exhibited multiple peaks (n > or = 2) on the plasma concentration-time curve.
      Although food did not affect the bioavailability of this formulation, there was a
      statistically significant increase in the mean (+/-SE) concentration of the first
      peak (Cpeak 1) from 14.21 +/- 1.38 mg L-1 (fasting) to 20.14 +/- 1.38 mg L-1
      (with food). The time at which Cpeak 1 was reached was not influenced by the
      intake of food. Results indicate that while qualitative changes in the plasma
      concentration versus time curves are primarily influenced by the nature of the
      formulation and the type of meal, bioavailability is influenced by the absorption
      characteristics of the drug as well. Thus, despite a significant increase in peak
      plasma concentrations of both drugs with a meal, the bioavailability of
      flurbiprofen alone was enhanced.

PMID- 8866043
TI  - Five modified numerical deconvolution methods for biopharmaceutics and
      pharmacokinetics studies.
AB  - Four improved finite-difference numerical deconvolution methods and one nonlinear
      regression numerical deconvolution method are proposed and implemented using
      IMSL/IDLTM. These five numerical deconvolution methods are evaluated using
      simulated data generated with and without added noise under six different dosing
      cases. Comparisons between these methods are made in terms of the
      superimposability of the calculated cumulative amount of drug released or
      absorbed-time profiles with the theoretical data. The results indicate that the
      proposed fixed step number equal step length numerical deconvolution method is
      simple and accurate and therefore is appropriate for pharmacokinetic and
      biopharmaceutic studies. When an analytic function is legitimate to represent the
      drug input rate, the nonlinear regression numerical deconvolution method will
      yield enhanced numerical accuracy and stability.

PMID- 8866044
TI  - Dose-independent pharmacokinetics of the cardioprotective agent dexrazoxane in
      dogs.
AB  - A randomized, four-way cross-over design was used to assess the disposition of
      the cardioprotective agent, dexrazoxane, in four male beagle dogs following
      single I.V. administration of 10, 25, 50, and 100 mg kg-1 doses. Parent drug was
      quantified in plasma and urine with a validated high-pressure liquid
      chromatographic-electrochemical assay. A two-compartment open model adequately
      described the dexrazoxane plasma concentration versus time data. The terminal
      half-life ranged between 1.1 and 1.3 h and the apparent steady-state distribution
      volume was 0.67 L kg-1. The systemic clearance (CL) ranged from 10.3 to 11.5 mL
      min-1 kg-1, while estimates of renal clearance approximated the glomerular
      filtration rate (GFR approximately 3.2-4.9 mL min-1 kg-1). Over the dose range
      evaluated, CL was dose independent (ANOVA, p = 0.33), while concentration at the
      end of infusion (Cend) and the area under the concentration versus time curve
      (AUC) were directly proportional to the dose (r > 0.999). The blood cell to
      plasma partitioning ratio was approximately 0.517 and drug was essentially
      unbound to plasma proteins (fu approximately 0.95). Dexrazoxane appeared to be
      subject to low organ extraction, since the hepatic and renal drug extraction
      ratios were on the order of 0.228 +/- 0.054 and 0.184 +/- 0.024, respectively.
      These results suggest a relatively small drug distribution space (approximately
      equal to total-body water) and low tissue and plasma protein binding. In light of
      the low plasma protein binding and extraction ratio exhibited by dexrazoxane,
      metabolic capacity and renal function would appear to be the predominant
      variables affecting the CL of this drug. The constancy of the half-life, CL, and
      VSS with increasing dose indicates dose-independent disposition for dexrazoxane.
      Thus a linear increase in the systemic exposure can be predicted over this dose
      range.

PMID- 8866045
TI  - Intermittency route to chaos in a biochemical system.
AB  - The numerical analysis of a glycolytic model performed through the construction
      of a system of three differential-delay equations reveals a phenomenon of
      intermittency route to chaos. In our biochemical system, the consideration of
      delay time variations under constant input flux as well as frequency variations
      of the periodic substrate input flux allows us, in both cases, to observe a type
      of transition to chaos different from the 'Feigenbaum route'.

PMID- 8866046
TI  - Evolutionary strategies of stochastic learning automata in the prisoner's
      dilemma.
AB  - Stochastic learning automata (SLA) model stimulus-response species which receive
      feedback from the environment and adjust their mixed strategies in a Prisoner's
      Dilemma. A large heterogeneous population consists of SLA applying different
      strategies (i.e. different learning parameters) and other players applying
      deterministic strategies, Tit-For-Tat (TFT) or Always-Defect (ALLD). The
      predicted equilibria determine the payoffs within a generation for applying
      particular strategies and these equilibria are confirmed by simulation. The
      resultant population dynamics over many generations show that SLA with
      insensitive penalty responses strongly favor defection and dominate in subsequent
      generations over SLA with sensitive penalty responses. The SLA strategies are not
      evolutionarily stable as they can be invaded by TFT or ALLD. With the
      introduction of memory in the stimulus-response model, SLA learn to cooperate
      with TFT players.

PMID- 8866047
TI  - Sensitivity constraints in a chemical/biochemical highly responsive system.
AB  - The sensitivity properties of a reaction scheme that can show highly sensitive
      responses is studied (see e.g. Okamoto, M., Sakai, T. and Hayashi, K., 1987,
      Biosystems 21, 1-11). This model was previously proposed to represent a 'chemical
      diode', a 'chemical McCulloch Pitts neuron', the cycling of a cofactor or the
      interconversion of a covalently modifiable enzyme. The sensitivity of the steady
      state flux and concentrations with respect to changes in a rate is quantified by
      the control coefficient (CC). Two types of constraints reduce the sensitivity
      patterns that the model can exhibit: the structural and kinetic constraints. The
      existence of these constraints substantially reduces the number of CC that can
      show arbitrary values. For instance, under extreme kinetic constraints, the value
      of one CC suffices to determine the values of the other thirty nine. The
      dependent CC are obtained as a function of the independent CC in two particular
      cases: the chemical case, governed by simple mass action rate laws, and the
      biochemical case, catalyzed by saturable enzymes. It is shown that the
      biochemical case exhibits a qualitatively richer repertoire of sensitivity
      patterns than the chemical case. Although the strategy developed in this work is
      restricted to a particular model its application is general. The usefulness of
      this type of analysis in the solution of problems ranging from design of
      chemical/biochemical devices to evolution of metabolism is discussed.

PMID- 8866048
TI  - The hypercube structure of the genetic code explains conservative and non
      conservative aminoacid substitutions in vivo and in vitro.
AB  - A representation of the genetic code as a six-dimensional Boolean hypercube is
      described. This structure is the result of the hierarchical order of the
      interaction energies of the bases in codon-anticodon recognition. In this paper
      it is applied to study molecular evolution in vivo and in vitro. In the first
      case we compared aligned positions in homologous protein sequences and found two
      different behaviors: (a) There are sites in which the different amino acids may
      be explained by one or two 'attractor nodes' (coding for the dominating amino
      acid(s)) and their one-bit neighbors in the codon hypercube; and (b) There are
      sites in which the amino acids correspond to codons located in closed paths in
      the hypercube. In the second case we studied the 'Sexual PCR'1 experiment
      described by Stemmer [Stemmer (1994)] and found that the success of this
      combination of usual PCR and recombination is in part due to the Gray code
      structure of the genetic code.

PMID- 8866049
TI  - The change of microtubule length caused by endogenous AC fields in cell.
AB  - In this paper we investigate the change of microtubule cylinder's length in the
      presence of endogenous AC fields generated by the cell itself. The dynamics of
      microtubule is described on the basis of classical u4 model. The average
      stretching is calculated by using Kubo's formalism for linear response of system.

PMID- 8866050
TI  - The effects of variable biome distribution on global climate.
AB  - In projecting climatic adjustments to anthropogenically elevated atmospheric
      carbon dioxide, most global climate models fix biome distribution to current
      geographic conditions. Previous biome maps either remain unchanging or shift
      without taking into account climatic feedbacks such as radiation and temperature.
      We develop a model that examines the albedo-related effects of biome distribution
      on global temperature. The model was tested on historical biome changes since
      1860 and the results fit both the observed temperature trend and order of
      magnitude change. The model is then used to generate an optimized future biome
      distribution that minimizes projected greenhouse effects on global temperature.
      Because of the complexity of this combinatorial search, an artificial
      intelligence method, the genetic algorithm, was employed. The method is to adjust
      biome areas subject to a constant global temperature and total surface area
      constraint. For regulating global temperature, oceans are found to dominate
      continental biomes. Algal beds are significant radiative levers as are other
      carbon intensive biomes including estuaries and tropical deciduous forests. To
      hold global temperature constant over the next 70 years this simulation requires
      that deserts decrease and forested areas increase. The effect of biome change on
      global temperature is revealed as a significant forecasting factor.

PMID- 8866051
TI  - Self-organization in computer simulated selective systems.
AB  - In certain biologic systems, the signal selects functional or numerical expansion
      of the recognizing elements. Examples of these systems include the immune system,
      brain cortex, and evolution. One common feature of these Darwinian-type systems
      is degenerate recognition, in which one signal can recognize several different
      elements, with different affinities and consequences. For example, T cell antigen
      receptors and antibodies demonstrate relative but not absolute specificity of
      recognition. Thus, the variables of dose of the signal and affinity of the
      recognizing element modulate the outcome. Another feature of these systems is the
      ability to create self-organized patterns, which do not mirror the incoming
      signals. The hypothesis of this study is that degenerate recognition with
      subsequent selection of recognizing elements can explain self-organization of
      these systems. An entirely numerical model was explored, using the cellular
      automata approach. Three intrinsic features of a common selective system were
      incorporated into this model: a large number of recognizing elements;
      degenerative recognition of stimuli by these elements; and subsequent selection.
      Different numerical patterns of incoming stimuli were tested. The model showed
      self-organizing dynamics. Usually, the population of recognizing elements
      demonstrated an initial period of equilibrium, then a chaotic transitional state,
      and, finally, the bifurcational appearance of a stable self-organized pattern.
      The final resolution into a stable pattern can be either gradual or quasi
      saltational. I conclude that systems with a large number of recognizing elements,
      degenerative recognition, and selection of recognizing elements can self organize
      based upon the pattern of the incoming stimuli.

PMID- 8866052
TI  - Effect of time lag on non-living resource in a simple food chain.
AB  - This paper deals with a system of one non-living resource detritus, detritivores
      and their predators where time delay has been considered in the detritus
      formation. Local stability criteria are derived in the absence of delays.
      Conditions are derived under which there can be no change of stability whatever
      the value of time lag and finally we obtain criteria under which the system
      admits a finite number of stability switchings as the time lag increases.

PMID- 8866053
TI  - The origin of protein synthesis: on some molecular fossils identified through
      comparison of protein sequences.
AB  - Sequence data, even if only marginally significant, and evolutionary arguments
      suggest that a similarity may exist between class II aminoacyl-tRNA synthetases
      and proteins involved in the nonribosomal biosynthesis of peptide antibiotics,
      and more in general, those belonging to the family of adenylate-forming enzymes.
      If correct, this hypothesis of homology may imply that the first peptide
      syntheses might have occurred on phosphopantetheine molecules in a thioester
      world and/or on a variant of the coenzyme A (CoA) in an RNA world. Therefore,
      peptide synthesis probably evolved on tRNA-like molecules from the CoA (or a
      variant CoA molecule) that had the potential for nucleotide extension, that made
      possible the evolution to the current mechanism of protein synthesis. Our
      hypothesis on the existence of such homology implies that a series of
      evolutionary steps such as the existence of a primitive catalytic domain with
      poor substrate specificity towards both (amino acids + ATP + pre-CoA (and/or
      CoA)) and (amino acids + ATP + tRNA-like) molecules may have occurred. Therefore,
      the pre-CoA (and/or CoA) and the tRNA-like molecules were able to use this enzyme
      ambiguity for a certain period, thus giving weight to the scheme of evolutionary
      transitions mentioned above.

PMID- 8866054
TI  - Comparison between oral and written spelling in Alzheimer's disease.
AB  - Written and oral spelling were compared in 33 patients with Alzheimer's disease
      (AD) and 25 control subjects. AD patients had poorer spelling results which were
      influenced by orthographic difficulty and word frequency, but not by grammatical
      word class. Lexical spelling was also more deteriorated than phonological
      spelling. Moreover, oral spelling was more impaired than written spelling in AD
      patients, whereas no difference was present between oral and written spelling of
      controls. Analysis of spelling errors showed that, for controls, errors were
      predominantly phonologically accurate in both spelling tasks. Significantly, AD
      patients produced more phonologically accurate than inaccurate errors in written
      spelling, whereas these errors did not differ in oral spelling. In contrast to
      controls who produced more constant than variable responses in oral and written
      spelling, AD patients made more variable responses (words correctly spelled in
      one task but incorrectly in the other) and they showed many instances of variable
      errors (different misspellings from one spelling task to the other). Two stepwise
      regression procedures showed that written misspellings were specifically
      correlated with language impairment, whereas oral spelling errors were correlated
      with attentional and language disorders. These results suggest that AD increases
      the attentional demands of oral spelling process as compared to written spelling.
      This dissociation argues, either for a unique Graphemic Buffer in which oral
      spelling requires more attentional resources than written spelling or for the
      hypothesis of separate buffers for oral and written spelling.

PMID- 8866055
TI  - Electrophysiological correlates of noun-verb processing in adults.
AB  - Auditory event related potentials (ERPs) were recorded to a series of nouns and
      verbs while 16 adults watched videotaped scenes. The scenes depicted an
      individual using objects or performing actions that were either labeled or not
      named by the auditorily presented nouns or verbs. Electrodes were placed over the
      left and right hemisphere frontal, temporal, and parietal regions of the scalp.
      Analyses compared ERPs elicited by words that matched or failed to match the
      scenes. Marked changes were noted in the ERPs recorded from electrode placements
      across the two hemispheres in response to words that served two different
      syntactic functions. This procedure is viewed as a useful technique for use with
      younger subject populations.

PMID- 8866056
TI  - Competitive inhibition models of lexical-semantic processing: experimental
      evidence.
AB  - A modified Neisser word-search (search II) was administered to patients with
      Parkinson's disease (PD), and significant deficits were found. Given the
      assumption that the processes are lexical, we interpret the results as support
      for the claim that there is competition between semantically related words in
      speech production (Wheeldon, 1989). A related verbal task-switching experiment
      (continuous series II) is also presented. Although PDs are impaired on task
      switching, there are double dissociations between verbal task switching
      (continuous series II) and lexical retrieval (search II). The relationship
      between performance on these tasks and on verbal fluency is also addressed.

PMID- 8866057
TI  - Preserved semantic priming effect in alexia.
AB  - BH, a left-handed patient with alexia and nonfluent aphasia, was presented with a
      lexical-decision task in which words and pronounceable pseudowords were preceded
      by semantically related or unrelated picture primes (Experiment 1). In Experiment
      2, BH was given an explicit reading task using the word lists from Experiment 1.
      Performance on Experiment 2 disclosed severe reading deficits in both oral
      reading and semantic matching of the words to pictures. However, in Experiment 1,
      BH demonstrated a significant semantic priming effect, responding more accurately
      and more quickly to words preceded by related primes than by unrelated primes.
      The present results suggest that even in a patient with severe alexia, implicit
      access to semantic information can be preserved in the absence of explicit
      identification. The possibility of categorical gradient in implicit activation
      (living vs. nonliving) in BH was also discussed, which, however, needs to be
      clarified in the further investigation.

PMID- 8866058
TI  - Text comprehension training for disabled readers: an evaluation of reciprocal
      teaching and text analysis training programs.
AB  - We are particularly grateful to Dr. Annemarie Sullivan Palincsar for her helpful
      advice and generosity in sharing materials, procedures, and sample dialogues for
      use in the version of Reciprocal Teaching used in the present study. This
      research was supported by an operating grant to the first author from the Ontario
      Mental Health Foundation. We gratefully acknowledge the contributions of Janet
      Hinchley and Karen Steinbach in assisting with data collection and Nancy Benson,
      Carolyn Kroeber, and Karen Steinbach in assisting with data analysis. We thank
      Sheila Wroblewski and Rosemary Slyne for their contributions in program
      development and lesson planning. We are grateful to the Principals and staff of
      Winona and Jesse Ketchem Schools and the Toronto Board of Education for providing
      satellite locations and support for our programs. The enthusiasm and efforts of
      the 46 students enrolled in the present programs, and the cooperation and
      interest of their parents and teachers, are particularly acknowledged.

PMID- 8866059
TI  - The patient comes first.

PMID- 8866060
TI  - Stability of orthognathic surgery: a review of rigid fixation.
AB  - The use of rigid fixation with orthognathic surgery was greeted by both
      excitement and healthy concern when it began to find its way into the literature
      approximately 10 years ago. The purpose of this paper is to review the literature
      and make comments based on the experience of the senior author on whether one of
      the early premises was true. Has rigid fixation improved stability with
      orthognathic surgery? The authors chose to examine mandibular advancements
      treated with a bilateral sagittal split osteotomy and maxillary osteotomies
      treated with a Le Fort I osteotomy. When compared to wire osteosynthesis, rigid
      fixation has improved stability; however, the individual move associated with the
      osteotomy must be considered. In some cases, auxiliary techniques should be used
      to ensure stability. Condylar resorption with mandibular advancement continues to
      be an area of concern.

PMID- 8866061
TI  - Deafness and cholesteatoma complicating fracture of the mandibular condyle.
AB  - A case of posterior fracture-dislocation of the mandibular condyle which resulted
      in conductive deafness and cholesteatoma is presented. Initial management by
      condylectomy improved auditory canal patency but failed to prevent the
      development of cholesteatoma, necessitating mastoid surgery. Although major
      complications following fractures of the condyle are not common the need to
      consider the possibility of damage to the ear in such fractures is emphasised.

PMID- 8866062
TI  - Treatment of retrobulbar haemorrhage in accident and emergency departments.
AB  - Retrobulbar haemorrhage is a rare complication of orbital injury or surgery.
      After injury the first clinicians to see these patients are often the staff of
      accident and emergency departments. This survey was instigated after several
      patients had been referred to our care irreversibly blind. A multiple choice
      questionnaire was devised and sent to 90 doctors working in accident and
      emergency departments in Scotland. A total of 57 (63%) were returned of which 55
      were complete enough to analyse. The range of respondents was: consultants (n =
      6), associate specialists (n = 3), senior registrars (n = 3), registrars (n = 4),
      senior house officer (n = 35), and clinical assistants (n = 4). Twenty nine of
      the 35 senior house officers (83%) were unable to diagnose and treat retrobulbar
      haemorrhage. Most consultants, senior registrars, registrars and associate
      specialists were significantly better in the diagnosis and treatment of this
      condition (P = 0.001). We conclude that there is an unacceptably high incidence
      of blindness as a result of inappropriate diagnosis and treatment of retrobulbar
      haemorrhage. We have therefore designed a protocol for accident departments which
      should help reduce the incidence of blindness.

PMID- 8866063
TI  - An audit of mandibular fractures treated by intermaxillary fixation, intraosseous
      wiring and compression plating.
AB  - As the principles of rigid internal fixation and compression osteosynthesis were
      adopted by maxillofacial surgeons during recent years the time-honoured methods
      of intermaxillary fixation and intraosseous wiring have gradually been abandoned.
      We have reviewed our cases of mandibular fractures operated on in recent years
      and the changing trends in treatment.

PMID- 8866065
TI  - Maxillofacial injuries in multiply injured patients.
AB  - Experience in team management of multiply injured patients with maxillofacial
      injuries is reported. During 1992, out of 169 patients transferred to the Royal
      London Hospital, UK by the Helicopter Emergency medical Service 38 (22.4%) had
      injuries to the maxillofacial region, 17 of whom were scored on the Abbreviated
      Injury Scale (AIS) as having sustained facial AIS > 2. The median Injury Severity
      Score (ISS) was 22, while the ISS was 17.7 for survivors and 34.5 for those who
      died (chi 2 = 7.3, 0.05 < P > 0.02). Facial AIS (median 4) and facial AIS
      contribution to ISS were found to be poor indicators of severity of injury.
      Revised Trauma Score (RTS) and percentage probability of survival (Ps%) were
      found to be useful discriminators of severity of overall injuries. RTS compared
      between survivors and those who died was 0.05 < P > 0.02 (chi 2), while Ps% was
      0.01 < P > 0.001 (chi 2). It was concluded that the severity of maxillofacial
      injuries, and hence their contribution to total injury assessments, tended to be
      underscored. We propose that refined facial injury assessment methods be tested.

PMID- 8866064
TI  - Maxillofacial injuries in a group of South Africans under 18 years of age.
AB  - OBJECTIVE: To find out the incidence of maxillofacial injuries in South African
      children aged 18 years or less. DESIGN: Retrospective study of casenotes.
      SETTING: Six teaching hospitals affiliated to the University of Witwatersrand,
      Johannesburg, serving a population of about 5 million people. SUBJECTS: All 326
      children treated for facial injuries in the maxillofacial and oral departments of
      the six hospitals between 1 January 1989 and 30 June 1992. MAIN OUTCOME MEASURES:
      Classification of the types of injury, associated injuries, cause of the injury,
      and methods of diagnosis. RESULTS: Of the total of 4192 patients of all ages
      treated for facial injuries, 326 (8%) were within the age range of the study. The
      female:male ratio was 1:2.3. Most of the injuries (227, 70%) occurred in the 13
      18 age group, and assaults, fights and gunshot wounds accounted for 155 injuries
      (48%). Of the 326 children, 173 (53%) had single injuries and 153 (47%) had
      multiple injuries. Mandibular fractures were the most common (64%) followed by
      maxillomandibular fractures (25%). Violence was the most common cause of injury,
      as in the USA and Zimbabwe, but unlike the rest of the world in which it is motor
      vehicle accidents. Soft tissue injuries were the most common associated injuries,
      and conventional plain radiography was the usual investigation. CONCLUSION: The
      incidence of 8% compares favourably with those in other countries, but far too
      many injuries are the result of violence.

PMID- 8866066
TI  - Bilateral traumatic hypoglossal nerve paralysis.

PMID- 8866067
TI  - Unusual presentations of injuries associated with the mandibular condyle in
      children.
AB  - Condylar fractures are sustained commonly by children and are readily diagnosed
      in the main. Three case histories serve to illustrate the intricate anatomy of
      the area and how damage to it can produce unusual signs and symptoms which can
      mislead the unwary. Supplemental images, in particular coronal CTs, can be
      instrumental in arriving at the correct diagnosis and treatment.

PMID- 8866069
TI  - Combined radial forearm and pharyngeal flap for soft palate reconstruction.
AB  - The use of a free vascularised fascio-cutaneous radial forearm flap in
      combination with a cranially based pharyngeal flap for soft palate reconstruction
      has not been previously reported. We present the technique and illustrate its use
      in two cases of total and one case of subtotal soft palate reconstruction. The
      functional outcome is discussed with particular reference to nasal airway
      patency, speech and swallowing.

PMID- 8866068
TI  - A comparative review of 266 mandibular fractures with internal fixation using
      rigid (AO/ASIF) plates or mini-plates.
AB  - This study compares the internal fixation of mandibular fractures using either
      rigid 2.7 mm AO/ASIF plates or mini-plates. In the rigid plate group, 88
      fractures were fixed with 88 plates. In the mini-plate group, 116 fractures were
      fixed with 170 plates. All the cases were consecutive and were treated in two
      South Wales hospitals during a 3-year period from 1988 to 1991. The aetiology of
      injury, timing of surgery, site of fracture, antibiotic policy and demographic
      features were evenly distributed between the two groups but there was a higher
      incidence of females in the mini-plate group. Both plating systems were
      successful in restoring functional occlusion. Rigid plates avoided the use of
      postoperative elastics better than mini-plates but the difference was not
      significant. There was a significantly higher incidence (P = 0.013) of infection
      in the mini-plate (12.9%) compared with the rigid plate (2.3%) group but 7.9% of
      the rigid group developed facial nerve weakness. A significantly higher
      proportion of mini-plates needed to be removed (P = 0.00019). A better treatment
      outcome for angle and comminuted fractures was noted with rigid plates.

PMID- 8866070
TI  - Hand grip strength: an indicator of nutritional state and the mix of
      postoperative complications in patients with oral and maxillofacial cancers.
AB  - The aim of the study was to assess the reliability of hand grip strength as an
      indicator of nutritional state, and to see if it was of any value in the
      prediction of postoperative complications. One-hundred and twenty-seven patients
      who presented with oral and maxillofacial cancer were studied for measurement of
      hand grip strength, mid-arm muscle circumference, and creatinine-height index.
      Hand grip strength correlated well with mid-arm muscle circumference and
      creatinine-height index. Patients whose hand grip strength was < 85% of the
      control value developed significantly more postoperative complications than those
      in whom it was 85% or more (15/31 (48%) compared with 12/65 (18%), P = 0.004). In
      conclusion, hand grip strength is not only a useful, non-invasive indicator of
      skeletal muscle mass, but may also be of use in predicting postoperative
      complications.

PMID- 8866071
TI  - Polymorphous low-grade adenocarcinoma of parotid gland.
AB  - A case of polymorphous low-grade adenocarcinoma arising within the parotid gland
      is described. This appears to be only the second case of this distinctive
      neoplasm to have arisen ab initio within a major salivary gland. It displayed the
      relatively indolent course associated with this adenocarcinoma subtype and
      emphasises that this diagnosis now has to be considered in tumours of major
      salivary glands.

PMID- 8866072
TI  - The use of an information leaflet for patients undergoing wisdom tooth removal.
AB  - Attempts to inform the patient about surgical procedures have increased for the
      purposes of ensuring informed consent and improving satisfaction with the service
      provided. Leaflets are being used as an additional aid in general practice and in
      hospital units. However, such written information is seldom evaluated. This study
      was conducted to assess the influence of using an information leaflet for
      patients attending oral surgery clinics at a local dental hospital. Sixty-six
      patients were included in the study and invited to complete a questionnaire to
      assess knowledge of wisdom tooth removal at the time of examination and just
      prior to surgery. The validity of the knowledge measure had been previously
      tested. At 1 month follow-up a patient satisfaction questionnaire was completed
      by the sample. Patients were randomised at the examination appointment into four
      groups. The first group was provided with the leaflet and prompted to read it by
      the dentist (WTL + Prompt). The second group was given the leaflet but not
      prompted (WTL only). The two other groups acted as controls. The third group was
      provided with a dental health education leaflet with no prompting (Control 1).
      The fourth and final group was given no additional written material (Control 2)
      but provided with verbal information and routine warnings in a similar way to all
      other groups participating in the study. The WTL + Prompt Group showed increased
      knowledge on retest (P < 0.001). The WTL Group showed a trend to greater
      knowledge (P < 0.06) however the control groups showed no improvement (P > 0.5).
      Patient satisfaction, although greatest in the group given a leaflet without
      prompting, was not simply related to leaflet provision.

PMID- 8866073
TI  - Apocrine hidrocystoma: report of a case.
AB  - A case of apocrine hidrocystoma, mimicking a naso-labial cyst of the maxilla is
      reported. The histopathological features and treatment of these rare lesions is
      discussed.

PMID- 8866074
TI  - Primary subclavian-axillary vein thrombosis: consensus and commentary.
AB  - Fifteen multiple-choice questions concerning options in the management of primary
      subclavian-axillary vein thrombosis were discussed by a panel of experts and then
      voted upon by 25 attending vascular surgeons with a special interest in venous
      disease and considerable experience in subclavian-axillary vein thrombosis. The
      large majority favored, or agreed upon: (1) early clot removal for active,
      healthy patients with a need/desire to use the involved limb in work or sport;
      (2) catheter-directed thrombolysis as initial therapy; (3) further therapy based
      on follow-up positional venography; (4) surgical relief of demonstrated thoracic
      outlet compression after a brief period of anticoagulant therapy; (5)
      conservative therapy if post-lysis venogram showed either (a) no extrinsic
      compression or (b) a short residual occlusion; and (6) intervention for residual
      intrinsic lesions with over 50% narrowing. However, there was little unanimity
      regarding the most appropriate intervention for residual stenoses, with opinion
      split between surgical and percutaneous transluminal angioplasty. For residual
      symptomatic occlusion 66% favored jugular vein turndown; only 10% would perform
      first rib removal.

PMID- 8866075
TI  - Non-invasive testing for cerebrovascular disease.
AB  - Selecting the appropriate investigation for diagnosing occlusive cerebrovascular
      disease depends on the availability, cost, accuracy, invasiveness and the purpose
      of the test. Intraarterial digital subtraction angiography remains the gold
      standard, but for accuracy the stenosis should be measured rather than estimated.
      Duplex ultrasonography is almost as accurate and can additionally analyse plaque
      morphology. Of 2651 duplex tests carried out in our laboratory, 12.2% were for
      reversible ischaemic attacks, 2.7% for amaurosis, 12.1% for cervical bruit and
      4.3% for vertebrobasilar ischaemia. Duplex within 30 days of operation was
      carried out on 607 patients (22.9%) and surveillance on 1000 others (37.7%).
      Asymptomatic carotid stenosis > 60% should be confirmed by intra-arterial digital
      subtraction angiography, magnetic resonance angiography or spiral computed
      tomography angiography. For typical transient ischaemic attacks, duplex or
      angiography alone is adequate but when the clinical presentation is atypical, a
      confirming test is required. Routine preoperative brain computed tomography is
      not cost-effective, being equivalent to US$ 4300-11840 per perioperative stroke
      in our institution. Postoperative surveillance is justified, costing only US$ 505
      per patient over 4 years.

PMID- 8866076
TI  - Vena caval interruption in the prevention of pulmonary embolism.

PMID- 8866077
TI  - A prospective study to define the optimum rescreening interval for small
      abdominal aortic aneurysm.
AB  - A prospective study of 99 patients with small abdominal aortic aneurysms was
      undertaken using serial ultrasound to assess the optimum screening interval.
      Fifty-three patients had aneurysms measuring 2.5-3.9 cm and 46 patients aneurysms
      of 4.0-4.9 cm. Aneurysms measuring 2.5-3.9 cm were screened annually and those >
      4.0 cm every 6 months. There were eight deaths in the 2.5-3.9 cm group, none
      attributable to a ruptured aneurysm and five patients have had their aneurysm
      repaired. Nine patients died in the 4.0-4.9 cm group, one with a ruptured
      aneurysm measuring 5.6 cm at her previous screening visit and who was unfit for
      operation. No other patient had an aneurysm which ruptured between scans. There
      were seven elective repairs in this group. No patient died following elective
      operation in either group. The mean growth rate of aneurysms in the 2.5-3.9 cm
      group was 2.2 mm in the first year, 2.8 mm in the second and 1.8 mm in the third.
      Corresponding growth rates in the 4.0-4.9 cm group were 2.7 mm, 4.2 mm and 2.2
      mm. This study supports a policy of annual screening for aneurysms measuring 2.5
      3.9 cm and 6-monthly screening for those > or = 4.0 cm.

PMID- 8866078
TI  - Screening study of abdominal aortic aneurysm in a general population: lipid
      parameters.
AB  - The level of blood lipids and apolipoproteins in subjects being screened for
      abdominal aortic aneurysms have been investigated. As part of an ultrasound
      screening programme in a population of 65- to 75-year-olds, blood samples were
      collected from 1460 of 1504 subjects with a normal aorta (97.1%) and 69 of 70
      patients with an abdominal aortic aneurysm > 29 mm (99%). Samples were also taken
      from 22 of 27 patients (81%) with an ectatic aorta (26-29 mm). Total cholesterol,
      HDL-cholesterol, LDL-cholesterol, Apo-AI and Apo-B levels were significantly
      higher in women than in men (P < 0.01). Levels of HDL-cholesterol and Apo-AI were
      significantly lower in patients with an abdominal aortic aneurysm than in normal
      subjects (P < 0.001). The mean(s.d.) body mass index was 25.1(3.9) in women and
      25.5(3.2) in men with aneurysms and not significantly greater than that of normal
      subjects (25.2(3.61) and 25.2(3.38) respectively).

PMID- 8866079
TI  - Clinical and vascular laboratory determinants for outcome after infrainguinal
      atherectomy.
AB  - Three surgeons performed 180 atherectomy procedures in 161 patients using the
      Transluminal Extraction Catheter in 144 and the Auth Rotablator in 36. The
      primary patency rate was 55% at 1 year and 46% at 2 years, and failure was caused
      by stenosis in 28 (15.6%) and occlusion in 61 (33.7%) limbs. Multivariate Cox
      regression analysis showed significantly better outcome if the indication was
      claudication, the lesion was short or there was associated stenting. Vascular
      laboratory surveillance was performed in 93 limbs in 83 patients. Cox regression
      analysis in this subgroup also showed a significant relationship between outcome
      and the maximum peak systolic velocity from a duplex scan at the last study
      performed. Receiver operating characteristics curves showed that a raised maximum
      peak systolic velocity best predicted late failure (sensitivity 84%, specificity
      66% for > 200 cm/s; sensitivity 72%, specificity 84% for > 250 cm/s); the
      velocity ratio at the stenosis to that in the segment above or the resting
      ankle/brachial pressure index were less predictive. For 50 procedures studied in
      the vascular laboratory which remained successful to the end of the study,
      maximum peak systolic velocities were > 250 cm/s from the first postoperative
      study, suggesting residual stenosis in 6%, or increased to become > 250 cm/s by
      the last study, suggesting recurrent stenoses in 12%. For 43 procedures which
      were studied and later failed, velocities were > 250 cm/s from the first test in
      26% or increased to > 250 cm/s by the last test before failure in 40%. Vascular
      laboratory surveillance helps to predict outcome after atherectomy. Failure may
      be a result of residual disease from the time of the procedure or from
      restenosis. The apparent high incidence of clinically manifest or developing
      stenoses raises doubts as to the benefit of atherectomy over balloon dilatation
      alone.

PMID- 8866080
TI  - Ischaemia of the hand after radial artery monitoring.
AB  - Percutaneous radial artery cannulation is commonly used for continuous monitoring
      of blood pressure and estimation of arterial blood gases. The purpose of this
      study is to define the incidence of radial artery thrombosis and associated hand
      ischaemia after cannulation. A prospective study of 40 patients who underwent
      radial artery cannulation was carried out with patients examined before and after
      cannulation for radial and ulnar pulses. Doppler waveforms, and finger/brachial
      and finger/wrist pressure indices were obtained. After cannulation 27.5% of
      patients developed abnormal radial artery flows with 10% having absent pulses and
      none having any symptoms of hand ischaemia. Radial artery cannulation is a safe
      procedure when performed properly and is associated with a very low incidence of
      hand ischaemia, despite a 27.5% incidence of abnormal radial artery flow after
      cannulation.

PMID- 8866082
TI  - Revascularization of the ischaemic hand using in situ veins.
AB  - Chronic severe ischaemia of the upper limb is rare, due to the low incidence of
      arterial disease and to the presence of an adequate pre-existent collateral
      network. However, sometimes it occasionally occurs, dictating the need for
      revascularization. Since 1990, the authors have revascularized five upper
      extremities with severe ischaemic changes, employing the cephalic and/or basilic
      veins, used in situ. The aetiology of the arterial disease was autoimmune in one
      case and late sequelae of trauma in the others. Of the in situ venous bypasses
      performed, three were brachial-radial, and two sequential grafts (one axillary
      radial-ulnar and one axillary-brachial-radial-ulnar). One concomitant
      sympathectomy was performed. All patients had excellent early and late results
      which leads the authors to recommend such revascularization of the forearm and
      hand, especially in the presence of severe ischaemia.

PMID- 8866081
TI  - The role of low-density lipoprotein apheresis as postoperative care of bypass
      grafting for chronic arterial occlusion.
AB  - Since November 1989, low-density lipoprotein apheresis has been applied to
      patients with intractable hyperlipidaemia following bypass grafting for chronic
      arterial occlusion of the lower extremities. The treatment group comprised six
      patients (four men, two women) with arteriosclerosis obliterans. In five
      patients, the ankle pressure index deteriorated and intermittent claudication
      recurred due to atherosclerotic progression. Results of low-density lipoprotein
      apheresis were dramatic; the deteriorated ankle pressure index and intermittent
      claudication improved significantly after several applications of low-density
      lipoprotein apheresis. Significant angiographic improvement was obtained in two
      patients. It is concluded that low-density lipoprotein apheresis appears to be an
      efficient method to preserve graft patency and treat postoperative patients with
      deteriorated ankle pressure index.

PMID- 8866083
TI  - Effects of ischaemia and reperfusion on vasoactive neuropeptide levels in the
      canine infrarenal aortic revascularization model.
AB  - Infrarenal aortic cross-clamping is associated with remote vascular events,
      including myocardial infarction and renal insufficiency. The purpose of this
      study was to determine whether hindlimb ischaemia and reperfusion associated with
      infrarenal aortic cross-clamping results in the production of vasoactive
      regulatory neuropeptides. A canine model of infrarenal aortic cross-clamping was
      used for the study. Serial blood samples were drawn, prior to, at the time of,
      and serially following placement of the clamp and subsequent release of the clamp
      and reperfusion. Ischaemia resulted in increased mean(s.e.m.) plasma levels of
      neuropeptide Y (NPY) (initial 10.0(1.8) pmol/l versus ischaemia 24.7(2.3) pmol/l,
      P < 0.001) and vasoactive intestinal polypeptide (VIP) (initial 2.53(0.5) pmol/l
      versus ischaemia, 7.3(1.3) pmol/l, P < 0.05). Reperfusion produced three-fold
      elevation of VIP (initial 2.5(0.5) pmol/l versus reperfusion 9.6(1.5) pmol/l, P <
      0.001), two-fold elevation in the plasma levels of endothelin-1 (initial 1.3(0.1)
      pmol/l versus reperfusion maximum 2.5(0.3) pmol/l, P < 0.01) and NPY (initial
      10.0(0.8) pmol/l versus reperfusion maximum 23.9(2.3) pmol/l, P < 0.001).
      Ischaemia and reperfusion did not alter calcitonin gene-related peptide (CGRP) (a
      potent vasodilator) levels. Endothelin-1 (ET-1) plasma levels were also increased
      following haemorrhagic shock (initial 1.3(0.1) pmol/l versus exsanguination
      3.4(0.4) pmol/l, P < 0.001), but not during ischaemia (initial 1.3(0.1) pmol/l
      versus ischaemia maximum 1.7(0.2) pmol/l, P = 0.7). It was concluded that
      vasoactive regulatory peptides are released following ischaemia, reperfusion and
      shock in the canine infrarenal aortic revascularization model and, therefore
      could contribute to remote vascular events observed with infrarenal aortic cross
      clamping.

PMID- 8866085
TI  - Recurrent femoral anastomotic false aneurysms: is long term repair possible?
AB  - This study was undertaken to evaluate the operative problems and the fate of
      patients operated on for recurrent femoral anastomotic false aneurysms, following
      aortofemoral bypass. It was found that 58 of 66 anastomotic false aneurysms which
      developed after aortoiliac or aortofemoral reconstruction were located at the
      femoral level, six at the anastomosis of the graft to the aorta and two at the
      iliac artery anastomosis. Six recurrences developed after surgical repair of
      femoral anastomotic false aneurysms but there were none after repair of aortic or
      iliac anastomotic false aneurysms. Of the six recurrences one patient was treated
      by direct repair and the remaining five by interposition of a prosthetic graft.
      There were no ischaemic complications or recurrences in a mean of three years.
      Elective, repeated repair is therefore a successful method of treating
      anastomotic false aneurysms. Deep sutures should be inserted into the arterial
      wall, tension should be avoided by placing an interposition graft when necessary,
      using a careful aseptic technique. Patients should be told to avoid extreme
      extension and rapid flexion-extension of the hip joint for the rest of their
      life.

PMID- 8866084
TI  - Surgical treatment of infected thoracic and abdominal aortic aneurysms.
AB  - Twelve patients with infected aneurysms of the thoracic and abdominal aorta were
      evaluated. Aneurysmal location, aetiology, bacteriology and treatment modality
      were analysed to determine the relationship between these factors and outcome.
      Patients were divided into two groups based on the preoperative states of their
      infections. Group 1 patients (n = 7) underwent resection after resolution of
      their active infection. The causative organisms included Staphylococcus
      epidermidis (two cases). Salmonella spp. (one). Acinetobacter (one),
      Mycobacterium tuberculosis (one) and unknown organisms (two). Group 2 patients (n
      = 5) required urgent surgery because of uncontrolled sepsis despite intensive
      treatment with antibiotics. The causative organisms included Staphylococcus
      aureus (two cases). Pseudomonas aeruginosa (two) and Salmonella spp. (one). In
      group 1, three patients underwent closed en bloc excision of the aneurysm with in
      situ graft replacement, and four underwent partial resection with in-situ graft
      replacement. In group 2, three patients underwent resection of the aneurysm with
      ligation of aorta and extra-anatomic bypass, and two underwent in-situ graft
      replacement after debridement of infected tissue. Overall, patients in group 1
      had a mortality rate of 14% compared with 80% in group 2. These results suggest
      that the operative approach and method chosen to restore arterial continuity have
      less of an impact on outcome. The primary determinants of outcome are virulence
      of the infecting organism and the preoperative state of the infection.

PMID- 8866087
TI  - A prospective randomized study of abdominal aortic surgery without postoperative
      nasogastric decompression.
AB  - Nasogastric decompression following abdominal aortic aneurysmectomy or bypass,
      for 3-4 days, is a routine part of postoperative care in many centers. A
      prospective randomized study of 80 patients undergoing abdominal aortic surgery
      was performed in order to determine the necessity of prolonged nasogastric
      decompression. Patients were divided evenly between removal of the nasogastric
      tube upon tracheal extubation and retention of the tube until the passage of
      flatus. Preoperative risk factors, aortic cross-clamp time, estimated blood loss,
      length of procedure, length of intensive care unit stay, numbers of days with
      nasogastric tube, number of days until clear liquid and regular diets commenced,
      and the length of hospital stay were recorded for all patients. There were no
      significant differences in any of the measured variables between the two groups.
      The length of hospital stay was similar in both groups and three patients in each
      group required a nasogastric tube or reinsertion of one. In conclusion, the
      routine postoperative use of nasogastric tubes for abdominal aortic procedures is
      unnecessary.

PMID- 8866086
TI  - Aortobifemoral surgery induces complement activation and release of interleukin-6
      but not tumour necrosis factor-alpha.
AB  - The aim of the present study was to determine the inflammatory response by an
      extended analysis of complement in 16 patients undergoing aortobifemoral bypass
      surgery. The patients were randomized to receive either a bifurcated expanded
      polytetrafluoroethylene graft (n = 8; group I) or a collagen-impregnated knitted
      Dacron graft (n = 8; group II) to determine whether differences in graft surface
      properties might influence the inflammatory response during and after the
      procedure. The following components of complement: C1q, C4, C3, C3d, C5a and
      terminal complement complexes were all analysed. C-reactive protein and
      interleukin-6 were also determined to assess the acute phase response. The
      complement data were corrected for haemodilution, which was assessed from alpha 2
      macroglobulin concentrations. A significant decrease of C1q (P < 0.0001) and an
      increase in C5a (P < 0.0005) was observed in both groups. C4 and C3 levels showed
      slight fluctuations in group I, whereas in group II these proteins increased
      significantly (P < 0.05, P < 0.005, respectively) between 2 and 7 days after
      surgery. Terminal complement complexes remained unchanged in both groups.
      Interleukin-6 levels peaked at 12-24 h and the C-reactive protein at 24-72 h.
      Higher interleukin-6 levels (P < 0.05) were found in group II 6 h after surgery
      compared with group I; no release of tumour necrosis factor-alpha was identified.
      An early inflammatory response was found in all patients. The patterns of the
      complement proteins varied with a C1q depletion and a C5a increase, interpreted
      as complement activation. Whether the variations between the two graft groups
      represent any differences in graft surface properties has to be further
      elucidated.

PMID- 8866088
TI  - In situ arterial allografting for aortoiliac graft infection: a 6-year
      experience.
AB  - Between October 1988 and May 1994, all aortoiliac graft infections seen in the
      authors' service were treated by in situ arterial allografting after resection of
      any infected graft or tissue. Some 83 consecutive cases were treated; there were
      68 isolated primary prosthetic infections (82%) and 15 aortoenteric fistulae
      (18%). Emergency arterial allografting was performed in five cases (6%), elective
      allografting in 64 cases (77%) and elective allografting after emergency
      palliative revascularization using a temporary prosthetic graft in 14 cases
      (17%). Arterial allografts were harvested from cadavers as part of a programme to
      retrieve multiorgan transplant tissue. Fifteen patients (18%) died either intra-
      or postoperatively. Three died during the operation, one from septic shock and
      two from uncontrollable coagulopathy. Twelve patients died in the early
      postoperative period, from from septic shock, two from myocardial infarction, two
      from pneumonia, one from a pulmonary embolism, one from an intestinal infarction,
      one from recurrence of a duodenal fistula and one from disruption of the native
      aorta at the suture line. Three patients presented with an early complication
      directly related to the use of the allograft. Eleven early survivors of the
      series died during follow-up. Among these late deaths, only one could likely be
      allograft-related. In four patients, the aortic segment of the allograft was
      mildly dilated on late computed tomography scan; three were reoperated on for
      disruption of the extra-abdominal segment of their allograft. All four cases were
      managed with simple suture of the allograft or with the use of a new allograft.
      Fifteen patients exhibited 19 late occlusive lesions of their allograft; 17 of
      these lesions had to be treated either with transluminal angioplasty or with
      surgery using autogenous or allograft material. In all but one case, secondary
      patency could be achieved through these additional procedures. Late occlusive
      disease was more prevalent in the femoral segment of the allograft than in the
      iliac or, moreover, the aortic segment. There were no late amputations in this
      series.

PMID- 8866089
TI  - Radical open endvenectomy with autologous pericardial patch graft for correction
      of Budd-Chiari syndrome.
AB  - A surgical technique for the treatment of Budd-Chiari syndrome associated with
      vena caval obstruction has been devised. The occluded hepatic vena cava and
      hepatic veins were reconstructed by open endvenectomy, using an autologous
      pericardial patch graft and a femorofemoral bypass technique. The hepatic artery
      and portal vein were not controlled with vascular clamps during the surgery.
      Between 1979 and 1994, 29 patients were treated using this technique and achieved
      good results. All the patients did well with good function of the reconstructed
      vena cava and of the hepatic veins, and showed acceptable reduction of symptoms
      caused by portal hypertension and caval stagnation.

PMID- 8866090
TI  - A prospective study comparing duplex scan and venography for diagnosis of lower
      extremity deep vein thrombosis.
AB  - This study was designed to compare duplex scanning with contrast venography for
      the diagnosis of acute deep vein thrombosis of the lower extremity, both at the
      femoropopliteal (above-knee) and tibioperoneal (below-knee) levels. A total of
      216 patients with 220 limbs suspected of acute deep vein thrombosis underwent
      duplex scanning followed within 24 h by ascending venography. The two studies
      were interpreted independently by two physicians who were blinded to the results
      of the corresponding alternative study. Venography was positive for deep vein
      thrombosis in 44.5% of cases (98/220). Duplex scanning was inadequate at the
      above-knee level in two cases (0.9%) and at the below-knee level in 17 cases
      (7.7%). Sensitivity and specificity of duplex scanning at above-knee level were
      98.7% and 100% respectively while corresponding values were 85.2% and 99.2% at
      below-knee level. By excluding technically inadequate duplex studies, the
      sensitivity at below-knee level was clearly improved (93.8%). It is concluded
      that with meticulous technique, duplex scanning is highly accurate in diagnosing
      acute deep vein thrombosis of symptomatic lower extremities, avoiding contrast
      venography in over 90% of the cases, even at the tibioperoneal level.

PMID- 8866091
TI  - A technique for the creation of long autogenous tissue arterial patches.
AB  - An endarterectomized segment of an occluded artery (e.g. superficial femoral
      artery), is an alternative autogenous material for patch angioplasty which
      preserves the continuity of the saphenous vein. A technique of incising
      endarterectomized segments of superficial femoral artery in a spiraled manner is
      presented which allows for the creation of long autogenous tissue patches. A
      spiral is drawn on the exterior of a harvested arterial segment which is either 1
      cm, 7 mm or 5 mm in width. When incised along the spiral, the length of the
      resulting elliptical patch will be two, three, or four times, respectively, the
      length of the original artery segment. The authors have used the technique to
      close extended profundoplasty in three patients and for construction of a patched
      distal anastomosis in two patients undergoing prosthetic femoropopliteal bypass
      grafting. There have been no early complications.

PMID- 8866092
TI  - Extraluminal endoscopic-assisted ligation of venous tributaries for infrainguinal
      in situ saphenous vein bypass: a preliminary report.
AB  - In an attempt to obviate the need for an incision the length of the leg during in
      situ saphenous vein bypass, a minimally invasive operation using 'laparoscopic
      techniques' was developed. At operation, standard incisions were made over the
      proximal femoral artery/vein and the saphenous vein at the distal popliteal
      artery level. An angioscopic valvulotome was used to perform valvulotomy under
      direct vision. After valvulotomy, a distention balloon system was used to form a
      'pocket' into which a laparoscope was inserted. Trocars were then inserted under
      direct vision and the saphenous vein dissected and side branches individually
      clipped. After occlusion of the venous side branches, proximal and distal
      arterial anastomoses were performed in the standard fashion. This minimally
      invasive operation using laparoscopic techniques precludes the need for a long
      leg incision and saphenous vein dissection, except at the proximal and distal
      arterial anastomoses.

PMID- 8866094
TI  - Continuous venovenous haemofiltration in neonates with renal insufficiency
      resulting from low cardiac output syndrome after cardiac surgery.
AB  - Acute renal insufficiency is a common complication after surgery for congenital
      cardiovascular defects in neonates and is associated with a high incidence of
      morbidity and mortality. The authors reviewed their experience with continuous
      venovenous haemofiltration in neonates and infants with acute renal insufficiency
      resulting from low cardiac output following cardiovascular surgery. Twelve
      critically ill patients with pharmacologically intractable fluid overload were
      treated with continuous venovenous haemofiltration over a period of 42 months.
      All patients were mechanically ventilated and dependent on high doses of
      catecholamines. Continuous venovenous haemofiltration was started 64.2(28.2) h
      postoperatively and maintained for a period of 8 to 195 h. A negative fluid
      balance was achieved in all patients (2.1(0.5) ml/kg per h). No complications
      relating to continuous venovenous haemofiltration were evident during the
      treatment. The survival rate was 59% (seven of 12). Continuous venovenous
      haemofiltration is a valid and simple method for controlling fluid overload in
      neonates and infants with low cardiac output.

PMID- 8866093
TI  - Effects of aprotinin on plasma levels of neutrophil elastase and postoperative
      blood loss in cardiac surgery.
AB  - This study evaluated the effects of aprotinin on plasma levels of elastase,
      platelet count, fibrinogen levels and postoperative bleeding. Thirty cardiac
      surgery patients were randomly chosen for this study. The protease inhibitor
      aprotinin was given in high doses to 20 patients before and during
      cardiopulmonary bypass; 10 patients served as the control group. Mean patient age
      and body weight was similar in both groups. There were no significant inter-group
      differences in the total cardiopulmonary bypass and cross-clamp times. Mean
      (s.e.m.) elastase levels were significantly raised in the control group
      (161.9(2.57) micrograms/l) compared with the treated group (148.2(3.29)
      micrograms/l) at 30 min of cardiopulmonary bypass (P < 0.01) and rose even
      further at the end of cardiopulmonary bypass, after protamine infusion, and 24 h
      postoperatively (P < 0.001). Platelet counts decreased more in the control group
      (P < 0.001). Serum fibrinogen levels were significantly lower in the controls
      during and just after cardiopulmonary bypass (P < 0.01). Postoperative blood loss
      was significantly less in the aprotinin-treated patients (315(25) ml) compared
      with the controls (589(154) ml) (P < 0.05). Aprotinin appears to inhibit elastase
      release and decrease postoperative blood loss.

PMID- 8866095
TI  - What are the limits for the Ross operation?
AB  - The Ross operation is physiologically the best approach for aortic valve
      replacement. At the Hospital de Santa Cruz 22 consecutive pulmonary autograft
      operations have been performed in patients with a mean age of 49 (range 17-65)
      years. Six patients had mitral valve disease, two had aortic aneurysms and one
      had a ventricular septal defect. Subcoronary implantation of the autograft was
      performed in 20 patients. A partial inclusion aortic root replacement technique
      was used in one and the aortic root was replaced in another. There were no
      hospital or late deaths. Two patients required autograft replacement at 3 and 9
      months postoperatively because of regurgitation. One of these cases was caused by
      an abnormality of the pulmonary valve and since then echocardiographic
      assessments of this valve have been performed routinely and have detected
      significant pulmonary incompetence in four patients who otherwise would have been
      operated on using the Ross procedure.

PMID- 8866096
TI  - Mitral valve replacement after percutaneous transvenous mitral commissurotomy.
AB  - Percutaneous transvenous mitral commissurotomy is widely performed as the first
      choice of the non-pharmacological treatments for mitral stenosis. Five patients
      have been identified who required mitral valve replacement after percutaneous
      transvenous mitral commissurotomy. The causes leading to mitral valve replacement
      were mitral regurgitation in three cases and insufficient commissurotomy in two.
      Massive mitral regurgitation is one of the most serious complications of
      percutaneous transvenous mitral commissurotomy. This report aims to elucidate the
      mechanism of massive mitral regurgitation occurring during percutaneous
      transvenous mitral commissurotomy. In every such case, there was a large tear in
      the posterior leaflet without any split in the commissures. The Japanese
      literature reports that 16 patients have undergone mitral valve replacement for
      massive regurgitation after percutaneous transvenous mitral commissurotomy: 14 of
      these cases had a tear in one of the leaflets and no evidence of splitting of the
      posterior commissure. These facts indicate that relative fragility of the
      leaflets as compared with rigidity of commissural fusion, especially in the
      posterior commissure, is an important factor of massive mitral regurgitation
      during percutaneous transvenous mitral commissurotomy.

PMID- 8866097
TI  - The stentless Toronto SPV bioprosthesis for aortic valve replacement.
AB  - The Toronto SPV bioprosthesis for aortic valve replacement has been prospectively
      evaluated in 100 patients, since March 1993. Intraoperative transoesophageal and
      postoperative transthoracic echocardiography were used to assess valve function.
      Follow-up was complete in 74 patients at 6 months and in 38 patients at 1 year.
      The average valve size implanted was 26.5 mm. Some 37 patients had additional
      coronary artery bypass grafting surgery. The hospital mortality rate was 4%. Non
      structural valve dysfunction occurred in one patient and late endocarditis in
      another patient required operation. There were no other valve complications. None
      of the patients developed clinically relevant aortic valve incompetence during
      follow-up and there was a significant decrease in pressure gradients, increase in
      valve orifice areas and decrease in left ventricular hypertrophy.

PMID- 8866098
TI  - The sheep as an animal model for heart valve research.
AB  - The first test used to assess new heart valve prostheses and devices is to
      implant them in a medium-sized animal. This is a costly piece of research and it
      is important to select the most appropriate animal. The authors feel that the
      sheep is an appropriate animal model for heart valve research and describe their
      experience in this area. It is hoped that the detailed description provided will
      be useful to any other group contemplating similar studies.

PMID- 8866099
TI  - Coeliac artery aneurysm: a case report.
AB  - Coeliac artery aneurysms are rare. A case of coeliac artery aneurysm treated
      successfully by endoaneurysmorrhaphy is presented. Although excision with
      arterial reconstruction is usually recommended, endoaneurysmorrhaphy can also be
      considered in selected cases.

PMID- 8866100
TI  - Aneurysm of the coeliac artery.
AB  - A case of coeliac artery aneurysm associated with multiple splanchnic artery
      aneurysms is reported. This abnormality involved the gastroepiploic and hepatic
      arteries. The coeliac artery was ligated at laparotomy and the liver
      revascularized by direct anastomosis of the common hepatic artery to the aorta.
      Arteriography on the fifth postoperative day showed a satisfactory result. The
      surgical problems associated with aneurysms of the coeliac artery are reviewed.

PMID- 8866101
TI  - Coeliac artery aneurysm: a case report.
AB  - Coeliac artery aneurysm is a rare but potentially fatal disease. In this paper a
      case of coeliac artery aneurysm is presented which was diagnosed before rupture
      and treated electively by resection and graft replacement between the aorta,
      common hepatic artery and superior mesenteric artery.

PMID- 8866102
TI  - Myocardial revascularization in a hemophiliac.
AB  - The case of a mild hemophiliac who underwent a successful and uncomplicated
      myocardial revascularization is presented. The procedures was safely performed
      while the patient was receiving factor VIIIC.

PMID- 8866103
TI  - Astringency of organic acids is related to pH.
AB  - Astringency and sourness of lactic, acetic and citric acids, each adjusted to pH
      3, 5 and 7, were evaluated in two experiments, one starting at equal
      concentrations in wt/vol before neutralization and the second starting at equal
      molarity. Astringency and sourness decreased with increasing pH. However, acids
      were differentially sour at equal pH, consistent with previous findings. In
      contrast, the tactile attributes associated with astringency (drying, roughing of
      oral tissues and puckery/tightening sensations) were similar across acids; pH was
      the major influence on astringency. Strong dependence on pH suggests that
      astringency of these acids is a direct result of their acidic properties, and not
      solely due to the hydrogen bonding mechanisms previously suggested as an
      explanation of astringency in tannin interactions with salivary proteins.

PMID- 8866104
TI  - Thermodynamic roles of solubility in taste responses of amino acids.

PMID- 8866105
TI  - Odor perception phenotypes: multiple, specific hyperosmias to musks.
AB  - Olfactory detection thresholds for 11 structurally diverse musk odorants and one
      non-musk odorant were obtained from 32 subjects. Hierarchical cluster analysis
      produced four groups of subjects. One group (n = 12) was uniformly sensitive to
      all musks; another (n = 16) was uniformly insensitive. Two groups of subjects
      contained otherwise insensitive individuals who were exceptionally sensitive to
      cyclopentadecanone and musk xylol (n = 2) and to delta9-hexadecenolactone and
      tonalid (n = 2) respectively. We propose that the latter two groups are odor
      perception phenotypes (MSHM1 and MSHM2) that consist of multiple, specific
      hyperosmias to musk odorants.

PMID- 8866106
TI  - Some basic psychophysics of calcium salt solutions.
AB  - Detection thresholds and the taste qualities of suprathreshold concentrations of
      calcium salt solutions were assessed. Average taste detection thresholds for
      calcium chloride (CaCl2), lactate (CaLa), hydroxide, phosphate and gluconate
      ranged between 8 and 50 mM, with no reliable differences among the various salts.
      Between-subject variability ranged over four orders of magnitude and reliability
      coefficients for repeated detection threshold tests of CaCl2 averaged r = 0.52.
      In an odor detection test, subjects could reliably discriminate 100 but not 1 mM
      CaCl2 and CaLa from water. The taste of suprathreshold concentrations (1-100 mM)
      of CaCl2 and CaLa was considered unpleasant. At 1 mM, CaCl2 solution was rated as
      35% bitter, 32% sour, 29% sweet and 4% salty. At higher concentrations the sweet
      component diminished and the salty component increased, so that 100 mM CaCl2 was
      rated as 44% bitter, 20% sour, 1% sweet and 35% salty. CaLa solutions were
      considered to be significantly less bitter and marginally more sour than
      equimolar CaCl2 solutions. Thus, the taste of calcium varied with both the form
      and concentration of salt tested, but included both sour and bitter components.
      Saltiness was identified only in high (> or = 32 mM) concentrations of CaCl2, and
      thus was not necessarily a component of calcium taste.

PMID- 8866107
TI  - Multiple human taste receptor sites: a molecular modeling approach.
AB  - Numerous experimental data on the human peripheral taste system suggest the
      existence of multiple low-affinity and low-specificity receptor sites which are
      responsible for the detection and the complete discrimination of a very large
      number of organic molecules. According to this hypothesis, a given molecule
      interacts with numerous taste receptors and vice versa. Statistical analysis of
      taste intensities estimated by 58 human subjects for various molecules enables
      the calculation of taste intermolecular distances. For the present modeling
      study, we hypothesized that a short taste distance (i.e. taste similarity)
      between two distinct molecules indicates that they bind with similar
      distributions of affinities to the taste receptors, and hence display similar
      binding motifs. In order to find common molecular binding motifs among 14
      selected organic tastants, hydrogen-bonding and hydrophobic interaction
      properties were mapped onto their molecular surfaces. The 14 surfaces were then
      cut in 240 fragments, most of which were made up of 2-4 potentially interacting
      zones. A correspondence index was defined to measure the analogy between two
      optimally superimposed fragments. The 75 most representative fragments were all
      matched pairwise. Twelve distinct clusters of fragments were isolated from the
      2775 calculated comparisons. These 12 fragment types were used to calculate
      structural similarity distances. We then performed a combinatorial analysis to
      identify which fragment combination best reconciled structural and taste
      distances. We finally identified an optimal subset of seven fragment types out of
      the 12, which significantly and best accounted for the 91 pairwise taste
      distances between all 14 modeled tastants. These seven validated fragment types
      are therefore presented as good candidates to be recognized by the same number of
      distinct taste receptor sites. Potential applications of these identified binding
      motifs to tastant design are suggested.

PMID- 8866108
TI  - Odor perception and beliefs about risk.
AB  - Although the perceptual response to environmental odors can be quite variable,
      such variation has often been attributed to differences in individual
      sensitivity. An information-processing analysis of odor perception, however,
      treats both the reception and the subsequent evaluation of odor information as
      determinants of the perceptual response. Two experiments investigated whether a
      factor that influenced the evaluation stage affected the judgement of odor
      quality and the degree of adaptation to the odor. People were surveyed in order
      to measure their tacit perceptions of the healthfulness or hazardousness of nine
      common olfactory stimuli, and the instructional context influenced quality
      perception. In a second experiment subjects were exposed to an ambient odor under
      one of three different conditions, and odorant characterization influenced the
      degree of adaptation to the odor. Subjects who were led to believe the odor was a
      natural, healthy extract showed adaptation; those told that the odor was
      potentially hazardous showed apparent sensitization; while those told that the
      odor was a common olfactory test odorant showed a mixed pattern: some exhibited
      adaptation, whereas others showed sensitization. However, detection thresholds
      obtained before and after exposure showed adaptation effects that are
      characteristic of continuous exposure. These findings raise the possibility that
      cognitive factors may be modulating the overall sensory perception of odor
      exposure (i) for some individual who exhibit extreme sensitivity to odors and
      (ii) in situations where adaptation to environmental odors is expected but does
      not occur.

PMID- 8866109
TI  - Specificity of glossopharyngeal nerve responses to astringent compounds in
      Xenopus.
AB  - Astringent compounds were applied to oral epithelium of the clawed toad, Xenopus
      laevis, and rapidly rising and highly sensitive responses could be recorded from
      the whole glossopharyngeal nerve, but not at all from the trigeminal nerve. The
      response to 10 mM tannic acid decreased progressively with repetitive
      application. These responses to tannic acid, however, recovered completely by
      treating with chemicals capable of forming strong hydrogen and hydrophobic bonds.
      These chemical bondings are generally recognized as a model for polyphenol
      (tannin)-protein interactions based on physico-chemical measurements in vitro.
      The high affinities of these chemicals for tannic acid may be effective in
      releasing both bonds in the interaction of tannic acid with the receptor
      molecules. Our results provide in vivo evidence for this model.

PMID- 8866110
TI  - Phagocytic cells in the taste buds of rat circumvallate papillae after
      denervation.
AB  - Phagocytic cells in the taste buds of rat circumvallate papillae after the
      sectioning of bilateral glossopharyngeal nerves were examined by electron
      microscopy and immunohistochemistry. Electron micrographs taken 1 day after
      denervation revealed that flat-shaped cells were present just beneath the taste
      buds and that their cellular processes extended toward the debris from the
      degenerating taste buds. At 2-6 days after denervation, long and thin processes
      of the flat cells surrounded the debris and appeared to have taken them up into
      the cytoplasm as small vesicles. Evidence for phagocytosis by the flat cells was
      seen up to 9 days after denervation and again at 24 and 40 days, in correlation
      to the degeneration and regeneration of the taste buds. Pre-embedding
      immunohistochemistry using anti-vimentin antibody showed that flat cells strongly
      reacted with vimentin. Light microscopic immunohistochemistry using anti
      macrophage antibodies (ED1, ED2) showed that throughout the post-operative days
      macrophages were not present underneath or within the taste buds. Most of the ED2
      immunoreactive resident macrophages were located in the deep layer of connective
      tissue, and a few were found in the nerve bundle. ED1-immunoreactive cells were
      seen in the duct cells of von Ebner's glands and a few were in the trench wall of
      circumvallate papillae; however, they were also immunoreactive for anti-OX62
      antibody, which recognizes dendritic cells. The results indicate that the
      phagocytic cells of the taste buds are fibroblasts, not macrophages. Moreover,
      resident macrophages participate in phagocytosis of degenerated nerves together
      with Schwann cells.

PMID- 8866111
TI  - Pharmacokinetic studies of the fragrance compound 1,8-cineol in humans during
      inhalation.
AB  - The present study was undertaken to investigate the pharmacokinetics of 1,8
      cineol in human subjects during prolonged inhalation. The results showed that 1,8
      cineol is well absorbed from breathing air, with a peak plasma concentration
      after approximately 18 min. The elimination of this fragrance compound from the
      blood is biphasic, with a mean distribution half-life of 6.7 min and an
      elimination half-life of 104.6 min.

PMID- 8866112
TI  - Twenty years later: we do know how to prevent child abuse and neglect.

PMID- 8866113
TI  - Illness induction syndrome: paper I--a series of 41 children from 37 families
      identified at The Great Ormond Street Hospital for Children NHS Trust.
AB  - At the hospital 41 children from 37 families were identified as having had
      illness induced by a parent who in all but three cases was the mother. Their case
      records were reviewed. Four patterns of presentation occurred; failure-to-thrive
      through the active withholding of food; allegation of allergy and withholding of
      food; allegation and fabrication of medical symptoms; and active interference by
      poisoning or disrupting medical treatment. Four of the children died, two as a
      result of the illness induction. In 35% of the families a sibling had been
      previously subjected to some type of abuse. All the children had been presented
      with potentially serious symptoms, but post-identification only five were found
      to have serious medical problems requiring ongoing treatment. There were no
      specific characteristics of either the child or family associated with each type
      of presentation. Seventeen children had previously presented with failure-to
      thrive, feeding problems or food allergies. All the mothers had suffered at least
      one of the following: privation, child abuse, psychiatric illness, or significant
      loss or bereavement, whereas only half the fathers had grown up in a deprived
      family situation and/or had earlier or current health difficulties. Forty percent
      of the parents had serious marital problems. A combined medical/psychosocial team
      identified the abuse and attempted to understand the family's belief system
      regarding the illness. The process of Illness Induction was conceptualized as
      being initiated by the parents perceiving the child to be ill and using this
      focus on illness as a way of solving major personal, marital, and/or family
      difficulties.

PMID- 8866114
TI  - Type of maltreatment as a predictor of mental health service use for children in
      foster care.
AB  - This study examined predictors of utilization of mental health services among
      children and adolescents in foster care. Of particular interest was whether the
      type of maltreatment was related to utilization of services. Subjects were 662
      children ages 2-17 who were in foster care for at least 5 months. Service
      utilization, demographic, and behavioral data were collected through interviews
      with the subjects' caretakers. Type of maltreatment data were collected from
      Child Welfare case records. Fifty-six percent of the subjects had received mental
      health services. Children removed from their homes due to sexual and/or physical
      abuse were more likely to receive services than were those who were removed due
      to neglect and caretaker absence. Clinically significant behavior problems were
      associated with greater likelihood of receiving services, except for the sexually
      abused group who were very likely to receive services regardless of their
      behavior problem score. Sexually abused youth also received a higher number of
      outpatient visits than did neglected youth. In sum, youth who have experienced
      "active" types of maltreatment are more likely to receive mental health services
      than are those with "passive" types of maltreatment, even when the effect of
      severity of mental health problems is controlled.

PMID- 8866115
TI  - Attitudes toward physical discipline as a function of disciplinary history and
      self-labeling as physically abused.
AB  - To examine the relation between childhood experience with punitive discipline,
      perceptions of a punitive childhood history, and adult attitudes regarding
      appropriate discipline, a total of 1359 university undergraduates completed a
      screening questionnaire to assess their childhood disciplinary histories and
      their perceptions of that history. A sample of 207 of the screened participants
      who reported a diverse range of childhood disciplinary histories participated in
      a second test session to assess attitudes regarding appropriate discipline. Among
      persons with severely punitive histories, those who did not label themselves as
      abused were less likely to classify events as physically abusive than those who
      labeled themselves abused. Persons with less severe punishment histories were
      comparable to those with severely punitive histories who also labeled themselves
      abused. Additionally, persons who had experienced a specific form of physical
      discipline as a child were less likely to label that form of discipline abusive.
      However, this effect of experience did not obtain among subjects who described a
      history of discipline-produced injury. Implications of these patterns for the
      intergenerational transmission of abuse are discussed.

PMID- 8866116
TI  - Traumatic childhood events, perceived availability of emotional support, and the
      development of dissociative tendencies.
AB  - Past research has documented a link between childhood traumatic experiences and
      dissociative tendencies in adulthood. This study was undertaken to investigate
      the possibility that the previously reported link is purely an artifact of the
      level of emotional support available during childhood. A nonclinical sample of
      Australian adults was surveyed for the incidence of traumatic childhood events,
      the perceived availability of emotional support from intrafamilial and
      extrafamilial figures, and the presence of a dissociative coping style.
      Hierarchical regression analysis revealed that perceived availability of
      emotional support in childhood was a predictor of current dissociative
      tendencies, but account of the support factor did not eliminate the relationship
      between childhood trauma and dissociation. The data are consistent with the view
      that lack of emotional support is an important mediator, but not a primary cause,
      of the development of dissociative tendencies.

PMID- 8866117
TI  - The long-term sequelae of child and adolescent abuse: a longitudinal community
      study.
AB  - The purpose of the present study was to examine the relationship between
      childhood and adolescent physical and sexual abuse before the age of 18 and
      psychosocial functioning in mid-adolescence (age 15) and early adulthood (age 21)
      in a representative community sample of young adults. Subjects were 375
      participants in an ongoing 17-years longitudinal study. At age 21, nearly 11%
      reported physical or sexual abuse before age 18. Psychiatric disorders based on
      DSM-III-R criteria were assessed utilizing the NIMH Diagnostic Interview
      Schedule, Revised Version (DIS-III-R). Approximately 80% of the abused young
      adults met DSM-III-R criteria for at least one psychiatric disorder at age 21.
      Compared to their nonabused counterparts, abused subjects demonstrated
      significant impairments in functioning both at ages 15 and at 21, including more
      depressive symptomatology, anxiety, psychiatric disorders, emotional-behavioral
      problems, suicidal ideation, and suicide attempts. While abused individuals were
      functioning significantly more poorly overall at ages 15 and 21 than their
      nonabused peers, gender differences and distinct patterns of impaired functioning
      emerged. These deficits underscore the need for early intervention and prevention
      strategies to forestall or minimize the serious consequences of child abuse.

PMID- 8866119
TI  - The effects of sexual abuse on 3- to 5-year-old girls.
AB  - This study examined the initial effects of sexual abuse on 70 girls aged 3 to 5
      years. They were compared to a control group of 42 nonabused nonclinical girls
      matched for age. Of the 70 girls in the abused group, the 42 who had experienced
      intrafamilial abuse were also compared to the 28 who had experienced
      extrafamilial abuse. Evaluation of effects was based on maternal reports and very
      importantly, given this young age group, on direct observation. Children from
      both abuse groups displayed more evidence of distress on all measures. In
      particular, more sexual behaviors and more internalizing problem behaviors were
      reported and observed. Girls who were abused by a member of their family
      demonstrated some elevations in symptomatology, but generally there was not a
      significant difference between the two abuse groups. Poorer outcome was
      associated with a more noxious family environment and with repeated, more
      invasive abuse. The association of abuse and family characteristics that
      exacerbated the effects of sexual abuse on the child underscores the need for
      early detection and careful clinical assessment of the family as well as the
      child.

PMID- 8866118
TI  - Interviewing for sexual abuse: reliability and effect of interviewer gender.
AB  - An interview to detect histories of sexual abuse was administered to consecutive
      attenders at a gynecology clinic on two occasions, on one occasion by a male
      interviewer and on the other by a female interviewer. Fifty-six subjects were
      assessed, and at least partial agreement was found in 70% between the two
      interviews. Approximately one-third of incidents were reported at only one of the
      interviews, with gender of interviewer making little apparent difference to this.
      Contrary to expectation, subjects appeared more forthcoming at the first
      interview. Reasons for this are discussed. Interviews for sexual abuse must be
      carried out in an appropriate context, and simple routine screening questions may
      not be appropriate. Selection of interviewers on the basis of gender alone may
      not be helpful.

PMID- 8866120
TI  - Resilient child sexual abuse survivors: cognitive coping and illusion.
AB  - This research examined cognitive coping strategies associated with resilience in
      a nonclinical sample of child sexual abuse (CSA) survivors. In Study 1, 180
      college women completed surveys assessing self-enhancing cognitive distortions of
      reality, known as positive illusions, and CSA history. CSA survivors and
      nonvictimized women were found to be equally likely to engage in illusion, and
      for both groups, measures of illusion were strongly associated with psychological
      well-being. In Study 2, a qualitative study, a subsample of 20 CSA survivors from
      Study 1 were interviewed regarding their efforts to cope with CSA. Analysis was
      focused on comparisons between well-adjusted and poorly-adjusted women. The high
      adjustment group revealed a greater tendency to engage in four types of cognitive
      strategies: disclosing and discussing CSA, minimization, positive reframing, and
      refusing to dwell on the experience. The results of both studies highlight the
      importance of cognitive reappraisal in CSA recovery. Implications for therapists
      working with CSA survivors are discussed.

PMID- 8866121
TI  - Sexual dysfunction in males: significance of adverse childhood experiences.
AB  - This paper examines the impact of childhood sexual victimization, physical abuse,
      and dysfunctional family background on sexual dysfunctions in adulthood in a
      nonclinical male student sample. The current analysis is based on data from a
      survey by questionnaire from 301 males. Our findings show that (a) occasional
      sexual dysfunctions, especially premature ejaculation and sexual desire disorder,
      are frequent in young male adults; and (b) long-lasting adverse familial
      relationship to attachment figures are more influential to later sexual
      dysfunction than are childhood sexual abuse experiences.

PMID- 8866122
TI  - A process model for understanding adaptation to sexual abuse: the role of shame
      in defining stigmatization.
AB  - While sexual abuse in childhood places the individual at-risk for a variety of
      problems, research indicates wide variation in victims' adjustment. Limited work
      is available that attempts to systematically explain processes by which children
      adjust to the trauma. Few studies have been undertaken to examine any theory
      about what causes children to be symptomatic. This article presents a theoretical
      and testable model that specifies psychological processes related to the
      traumagenic dynamics of stigmatization in child and adolescent victims of sexual
      abuse. The model proposes that sexual abuse leads to shame through the mediation
      of cognitive attributions about the abuse and shame, in turn, leads to poor
      adjustment. Three factors, social support, gender, and developmental period are
      hypothesized to moderate the proposed stigmatization process. Developmental and
      clinical research supporting the model is reviewed, specific hypotheses are made,
      and the relevance of developmental psychopathology for future theory and research
      is discussed. Unless future research elucidates the process and circumstances
      whereby the experience of sexual abuse leads to poor adjustment, little progress
      will be made toward developing more effective treatments.

PMID- 8866123
TI  - Physician knowledge of child sexual abuse.
AB  - This study was undertaken to describe the knowledge about child sexual abuse, and
      factors that affect the knowledge of a statewide sample of physicians. A survey
      of physicians (n = 113) participating in a statewide program for child abuse
      evaluations was made in Summer 1993, with 78% participation. Knowledge scores
      were derived from the survey based on comparison to the responses of a panel of
      five experts. Several areas of inadequate knowledge were found including
      assessment of chlamydia infection, Tanner staging, and documentation of
      historical and physical exam findings. Factors associated with better knowledge
      scores were physician participation in continuing medical education and
      specialization in pediatrics. In addition, variations in presentation of the data
      affected physician judgement. We conclude that knowledge of physicians about
      child sexual abuse shows some deficiencies, is generally better among
      pediatricians, and may be improved by continuing medical education.

PMID- 8866124
TI  - Growth factors as drugs for neurological and sensory disorders. Introduction.

PMID- 8866125
TI  - Motor neuron disease and model systems: aetiologies, mechanisms and therapies.
AB  - The phenotypes of many neurological diseases, including motor neuron disease
      (amyotrophic lateral sclerosis; ALS) and Alzheimer's disease (AD), are determined
      by the vulnerabilities of populations of nerve cells and the character/ evolution
      of cellular abnormalities. Because different cell types respond selectively to
      individual trophic factors, these factors may be useful in ameliorating pathology
      in cells that express their cognate receptors. To test therapies for ALS and AD,
      investigators require model systems. Although there are a variety of models of
      ALS, two models are particularly attractive: transgenic mice that express human
      superoxide dismutase 1 (SOD-1) mutations linked to familial ALS develop paralysis
      associated with a gain of adverse property of the mutant SOD; and axotomy of
      facial axons in neonatal rats, a manipulation that causes retrograde cell
      degeneration, which can be ameliorated by several trophic factors.

PMID- 8866126
TI  - Potential utility of rhIGF-1 in neuromuscular and/or degenerative disease.
AB  - Neuromuscular/neurodegenerative disorders, such as the death of spinal cord motor
      neurons in amyotrophic lateral sclerosis (ALS) or the degeneration of spinal cord
      motor neuron axons in certain peripheral neuropathies, present a unique
      opportunity for therapeutic intervention with neurotrophic proteins. We have
      found that in mixed rat embryonic spinal cord cultures or in purified motor
      neuron preparations, recombinant human insulin-like growth factor 1 (rhIGF-1)
      enhances the survival of motor neurons at EC50 concentrations of 2 nM, consistent
      with an interaction at the tyrosine kinase-coupled rhIGF-1 receptor. In a model
      of programmed cell death in ovo, administration of rhIGF-1 produces a marked
      survival of motor neurons. In a variety of models of predominantly motor neuron
      or nerve injury in rodents, administration of rhIGF-1 prevents the death of motor
      neurons in neonatal facial nerve lesions, attenuates the loss of cholinergic
      phenotype in adult hypoglossal nerve axotomy and hastens recovery from sciatic
      nerve crush in mice. In a genetic model of motor neuron compromise, the wobbler
      mouse, rhIGF-1 (1 mg/kg s.c. daily) delayed the deterioration of grip strength
      and provided for a more normal distribution of fibre types. In addition, rhIGF-1
      (0.3-1.0 mg/kg s.c. daily) prevents the motor and/or sensory neuropathy in
      rodents caused by vincristine, cisplatinum or Taxol. These combined data indicate
      that rhIGF-1 has marked effects on the survival of compromised motor neurons and
      the maintenance of their axons and functional connections. They also suggest the
      potential utility of rhIGF-1 for the treatment of diseases such as ALS and
      certain neuropathies.

PMID- 8866127
TI  - Therapeutic potential of the neurotrophins and neurotrophin-CNTF combinations in
      peripheral neuropathies and motor neuron diseases.
AB  - Although they are clearly critical in ontogeny, a broader role is emerging for
      neurotrophic factors in the maintenance and regeneration of the mature nervous
      system. This is due to recent success in the molecular characterization of a
      significant number of novel neurotrophic factors, including the neurotrophin
      family members brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3 and
      NT-4/5, and ciliary neurotrophic factor (CNTF). Availability of these factors,
      elucidation of their receptor structure and creation of mutant mice lacking in
      expression of these factors has rapidly led to an understanding of their
      mechanisms of action and neuronal specificity. Thus, in addition to classical
      target-derived roles it now appears that, in the adult, neurotrophic factors may
      also function in autocrine/paracrine modes to maintain neuronal survival,
      regulate phenotype and orchestrate regenerative sprouting. Furthermore, two or
      more neurotrophic factors may act synergistically in these functions. This
      chapter reviews recent studies on: (a) the specificity of NT-3 for proprioceptive
      sensory neurons in vitro, and the ability of NT-3 to attenuate deficits arising
      from large-fibre sensory neuropathy; and (b) synergistic actions of BDNF and CNTF
      towards motor neurons in vitro and the ability of BDNF-CNTF co-treatment to
      arrest motor neuron disease in the Wobbler mutant mouse. The clinical potential
      of NT-3 in peripheral neuropathies and of BDNF-CNTF co-treatment in motor neuron
      disease is highlighted.

PMID- 8866128
TI  - Growth factor function in the development and maintenance of midbrain
      dopaminergic neurons: concepts, facts and prospects for TGF-beta.
AB  - Dopaminergic neurons of the nigrostriatal system are important in the control of
      motor performance and degenerate in Parkinson's disease. Therefore, in order to
      design novel strategies for the treatment of Parkinson's disease, it is important
      for us to understand their development, function, trophic factor requirements,
      plasticity and susceptibility to toxic influences. A large and still increasing
      number of growth factors have been implicated in the regulation of the survival
      and differentiation of dopaminergic neurons. These factors may also protect
      against a variety of toxic influences. On the basis of their localization,
      putative sources and mechanisms of actions, such growth factors fall into several
      categories: (i) local factors within the midbrain influencing proliferation,
      transmitter phenotype, migration, positioning and neurite growth of stem cells
      and early neurons; (ii) factors acting retrogradely from the striatum, which are
      responsible for intrastriatal sprouting and navigation of newly arrived axons as
      well as life-long maintenance of the dopaminergic nigrostriatal connection; (iii)
      factors coming into play when the system is toxically impaired; (iv) factors
      directly acting on dopaminergic neurons; and (v) factors provided by
      cytokinestimulated astroglia, microglia and neurons affecting dopaminergic
      neurons anterogradely. This article reviews actions of growth factors on
      dopaminergic neurons in vitro and in vivo, with a focus on members of the
      transforming growth factor (TGF)-beta superfamily. TGF-beta s may be particularly
      relevant to dopaminergic neurons, since they are expressed in the nigrostriatal
      system from early embryonic stages to adulthood and are significantly up
      regulated in response to lesions.

PMID- 8866129
TI  - Somatic gene therapy for nervous system disease.
AB  - Neurotrophic factors are target-derived molecules that prevent neuronal
      degeneration during development and, in some cases, during adulthood. They offer
      substantial promise as therapeutic agents in neurological disease by preventing
      cell loss and promoting axonal regeneration. However, the optimal means of
      delivering neurotrophic factors to the nervous system, and the CNS in particular,
      is an unresolved issue. Neurotrophic factors rarely influence only a single
      target neuronal population, hence broad delivery of neurotrophic factors to the
      nervous system may results in effects on multiple non-targeted neuronal
      populations. Ideally, neurotrophin delivery to the nervous system should be
      target-specific, regionally restricted, chronic, safe, well-tolerated and of
      sufficient concentration to elicit responses from target neurons. In this paper
      we discuss the use of somatic gene transfer methods to deliver neurotrophic
      factors to the CNS in a manner that seeks to meet the above criteria.

PMID- 8866130
TI  - Neurotrophic factors in the treatment of peripheral neuropathy.
AB  - Peripheral neuropathies are common and frequently debilitating disorders which
      may include various subpopulations of motor, sensory or autonomic neurons
      depending on the underlying aetiology. They are likely to be the first group of
      neurological disorders to be successfully treated with growth factors since
      peripheral nerves are accessible to proteins given systemically. Preclinical and
      ongoing clinical trials of nerve growth factor (NGF) suggest that it will be
      useful for the treatment of diabetic, toxic and compressive sensory neuropathies.
      At appropriate doses NGF has no significant side effects in humans. Since NGF
      administration to mature animals stimulates synthesis of brain-derived
      neurotrophic factor and perhaps other neurotrophins in peripheral nerves, the
      spectrum of neuropathies treatable with NGF is wider than might be predicted.
      Preclinical studies suggest that insulin-like growth factor 1 (IGF-1) will be
      useful for the treatment of mixed motor and sensory neuropathies. For example,
      IGF-1 treatment can prevent the experimental motor and sensory neuropathies
      caused by the antitumour drugs, vincristine and cisplatin. Other neurotrophic
      factors have also shown promise in preclinical trials. The successful use of
      growth factors in the treatment of peripheral neuropathies may provide the first
      true therapy for this previously untreatable and devastating group of
      neurological disorders.

PMID- 8866131
TI  - Growth factors in the treatment of degenerative retinal disorders.
AB  - There are currently a number of degenerative conditions, both inherited and
      acquired, that affect the retina and lead to blindness. Retinal photoreceptors
      degenerate from inherited conditions, such as retinitis pigmentosa or as a result
      of light damage or normal ageing; retinal ganglion cells degenerate from optic
      nerve injury or glaucoma. Current research in this field includes the use of
      growth factors to: (1) inhibit the degenerative processes; (2) promote
      regeneration of the retina from the pigmented epithelium; and (3) improve the
      conditions for transplantation of new cells to the retina by expanding the
      photoreceptor cell populations in vitro. The results to date have shown that a
      number of different growth factors promote survival of retinal cells in vitro and
      in vivo. In addition, some of the same factors can stimulate regeneration in the
      developing retina and act as mitogens for the retinal progenitor cells. It is
      likely that a combination of these approaches will ultimately be important for
      the treatment of the various retinal degenerations.

PMID- 8866132
TI  - Effects of neurotrophins on the survival and regrowth of injured retinal neurons.
AB  - The focus of this short review is the role of certain neurotrophins and their
      receptors on the survival and regrowth of retinal ganglion cells (RGCs) whose
      axons are damaged in the optic nerve. Initial experiments in our laboratory
      documented patterns of RGC death after axotomy. Subsequent studies were designed
      to investigate the distribution of high-affinity neurotrophin receptors in
      neurons and glial cells of the retina and optic nerve. This information was used
      both in vitro and in vivo to study the effects of specific trophic molecules on
      the survival and regrowth of injured RGCs. During the course of experiments
      involving neurotrophin administration, an endogenous source of trophic support-
      independent of the exogenous administration of growth factors--was found within
      the eye. Several experiments were subsequently undertaken to define further this
      survival effect and determine its nature and source within the eye. Finally,
      anatomical techniques that help visualize fine axonal processes within the retina
      have provided insights into the specific effects of neurotrophins on the growth
      and branching of injured CNS axons.

PMID- 8866133
TI  - Neurotrophic factors as pharmacological agents for the treatment of injured
      auditory neurons.
AB  - Mature auditory neurons degenerate in response to a loss of target-derived
      trophic factors. Neurotrophic factors influence the health and viability of
      auditory neurons. This suggests that neurotrophic factors can be used as
      therapeutic agents to prevent neuronal cell death and to initiate repair of
      damaged neuronal processes in the injured auditory system. Both in vitro and in
      vivo experiments have been performed to determine which of the vast array of
      neurotrophic factors affect mature auditory neurons and how they can be delivered
      to the sites of injury within the auditory system. Neurotrophin 3 was found to be
      a major survival factor for auditory neurons. Brain-derived neurotrophic factor
      is a minor survival factor for auditory neurons and nerve growth factor, although
      not promoting survival, does elicit the repair of neuronal processes. Fibroblast
      growth factor 2, transforming growth factor beta 1 and ciliary neurotrophic
      factor function as injury-response factors in the auditory system. Combination of
      different classes of growth factors has an additive effect on neuronal survival.
      Growth factors may be able to be delivered to sites of injury within the cochlea
      by either direct perfusion or gene therapy (e.g. a defective virus expressing a
      growth factor gene).

PMID- 8866134
TI  - Growth factors as potential drugs for the sensory epithelia of the ear.
AB  - The highly ordered structures of the hearing and balance organs of vertebrate
      ears go through a coordinated sequence of cellular and morphogenetic events. It
      is to be expected that protein growth factors and other extracellular signals
      will regulate many events during embryonic development of the ear, including the
      induction of the ear, the specific induction of sensory epithelia, the
      proliferation of the cells that form the sensory epithelia, the differentiation
      of the sensory and supporting cells, and the attraction and maintenance of
      innervation. After embryonic development, growth factors will support cell
      survival and innervation of new sensory cells. In damaged sensory epithelia,
      supplementation of the normal growth factors in these tissues has the potential
      to influence cellular responses to trauma, to reduce cell death and to promote
      the replacement of dead cells through renewed proliferation and differentiation,
      so as to improve hearing and balance health via preventive and restorative
      treatments. Assessment of the influences of specific growth factors on the
      sensory epithelia of vertebrate ears is at an early stage: this paper provides a
      brief account of what we know from studies of normal and experimentally
      manipulated epithelia, discusses the current questions and suggests directions
      for future studies.

PMID- 8866135
TI  - Factors affecting neuronal birth and death in the mammalian olfactory epithelium.
AB  - To identify factors regulating neurogenesis and neuronal death in mammals and to
      determine the mechanisms by which these factors act, we have studied mouse
      olfactory epithelium using two different experimental paradigms: tissue culture
      of olfactory epithelium purified from mouse embryos; and ablation of the
      olfactory bulb in adult mice, a procedure that induces olfactory receptor neuron
      (ORN) death and neurogenesis in vivo. Studies of olfactory epithelium cultures
      have allowed us to characterize the cellular stages in olfactory neurogenesis and
      to identify factors regulating proliferation and differentiation of precursor
      cells in the ORN lineage. Studies of adult olfactory epithelium have enabled us
      to determine that all cell types in this lineage-proliferating neuronal
      precursors, immature ORNs and mature ORNs-undergo cell death following olfactory
      bulb ablation and that this death has characteristics of programmed cell death or
      apoptosis. In vitro studies have confirmed that neuronal cells of the olfactory
      epithelium undergo apoptotic death and have permitted identification of several
      polypeptide growth factors that promote survival of a fraction of ORNs. Using
      this information, we have begun to explore whether these factors, as well as
      genes known to play crucial roles in cell death in other systems, function to
      regulate apoptosis and neuronal regeneration in the adult olfactory epithelium
      following lesion-induced ORN death.

PMID- 8866136
TI  - The problems of delivering neuroactive molecules to the CNS.
AB  - At present, the aetiologies of many neurological and neurodegenerative diseases
      are unknown. However, emergence of a better understanding of these diseases, at
      both cellular and molecular levels, opens up the possibility of replacement
      therapies. The presence of the blood-brain barrier complicates the delivery of
      molecules to the central nervous system. Numerous attempts have been made to
      bypass this barrier either by delivering the drugs directly into the brain or by
      transplanting cells to produce the missing molecules in situ. This review
      explores several methods for delivering bioactive molecules into the CNS,
      including the use of permeabilizers, osmotic pumps, slow polymer release systems
      and transplantation of cells with or without the use of the encapsulation
      technology.

PMID- 8866137
TI  - Near patient testing (NPT) in haemostasis--a synoptic review.

PMID- 8866138
TI  - Experience with the Port-A-Cath in sickle cell disease.
AB  - Peripheral vein access is often a problem in patients with sickle cell disease
      (SCD). Totally implantable venous access devices (TIVAD) have offered other
      groups of patients safe long-term venous access. We reviewed our own experience
      with the use of a Port-A-Cath device in five patients with SCD undergoing
      exchange transfusion programmes. All five lines required removal due to infection
      associated with SBE, septic arthritis, pulmonary embolus and axillary vein
      thrombosis. The organisms involved were Staphylococcus aureus (3), Staphylococcus
      epidermidis (1) and Streptococcus sp. (1). The median working life of the
      catheters was 240 days (range 61-428). The median length of time from
      presentation to the diagnosis of a line-associated infection was 29 days (range 1
      58). The rate of complications (0.4 per 100 patient days) in this small group of
      patients contrasts with the lower rates in patients with HIV and malignancy (0
      0.1 per 100 patient days). Our results suggest that patients with SCD suffer an
      unacceptable incidence of infective complications associated with the Port-A
      Cath. Bone infection is more common where there is pre-existing infarcted tissue.
      While these systems provide a valuable tool, our experience has led us to
      discontinue the use of TIVADs in SCD.

PMID- 8866139
TI  - The effects of a self-educating blood component request form and enforcements of
      transfusion guidelines on FFP and platelet usage. Queen Mary Hospital, Hong Kong.
      British Committee for Standards in Hematology (BCSH).
AB  - Despite establishment of transfusion guidelines and feedback intervention, FFP
      and platelet transfusion were still inappropriate in many clinical situations at
      our hospital. Many physicians never read or referred to the guidelines when they
      were ordering FFP and platelet transfusion. A new blood component request form
      with the guidelines printed on it was designed to facilitate physician education
      and enforcement of these transfusion guidelines. The form was well accepted by
      junior house staff and inappropriate transfusion was significantly reduced.

PMID- 8866140
TI  - Interference of blood leucocytes in the measurements of immature red cells
      (reticulocytes) by two different (semi-) automated flow-cytometry technologies.
AB  - Flow cytometrical methods have been introduced recently as an alternative to the
      enumeration of reticulocytes by microscopy. Two of these methods have gained
      widespread use in haematological practice; the multiparametric flow cytometer
      using thiazole orange staining (Retic-Count, FACScan) and the single-application
      reticulocyte counter using auramine-O staining (R-series, Sysmex). Several
      studies have emphasized the excellent correlations between microscopy and these
      techniques. The purpose of our study has been to examine the specificity of these
      automated devices with regard to cells classified as 'reticulocytes' and the
      effect that this may have on measures of reticulocyte maturity. Our results
      indicate that the specificity of reticulocyte measurements by both the Sysmex R
      1000/-3000 and the Retic-Count system is relatively low. This is due to the
      presence of leucocytes amongst cells classified as reticulocytes. These
      leucocytes display intense staining with either dye, leading to an erroneous
      estimation of RMI (thiazole orange) and high fluorescence count (R-1000/-3000).
      This error is directly correlated with the leucocyte count. The basis for
      reticulocyte identification should be improved before automated estimation of
      reticulocyte maturation can be used in clinical practice.

PMID- 8866141
TI  - Dual CD38 and DNA staining of plasma cells in monoclonal gammopathies attained by
      a rapid, non-wash and automated method.
AB  - Dual antigenic and DNA analysis are a prerequisite in order to study DNA content
      and cell cycle distribution accurately and identify, while studying them
      separately, neoplastic cells in the mixture of tumour samples with a high
      proportion of normal cells or when residual normal cells are highly
      proliferative. We describe a method for the simultaneous detection of surface
      CD38 antigen and study, by flow cytometry, of DNA content in the bone marrow of
      patients with a monoclonal gammopathy. This standardized, easy-to-perform, and
      automated flow cytometric non-wash technique allows dual antigen and DNA staining
      in less than 30 min. The method identifies bone marrow plasma cells and
      separately calculates their cell cycle distribution by means of a double staining
      technique for CD38 surface antigen and DNA content.

PMID- 8866142
TI  - Comparison of two methods to detect P-glycoprotein in patients with chronic
      lymphocytic leukaemia.
AB  - P-glycoprotein (Pgp) is a transmembrane protein associated with multiple drug
      resistance. Pgp can be detected by several monoclonal antibodies or its activity
      inferred by measuring drug uptake. We compared two methods for quantitating Pgp
      in 32 patients with chronic lymphocytic leukaemia. The monoclonal antibody 4E3,
      which recognizes an external epitope of Pgp, was detected by flow cytometry.
      Intracellular daunorubicin (DNR) accumulation was measured by flow cytometry in
      the presence (treated) and absence (control) of cyclosporin, an agent known to
      inhibit Pgp. Correlation between the degree of positivity on the drug uptake
      assay and Pgp detected by monoclonal antibody 4E3 was poor (r = 0.06). No
      association with previous drug exposure or lymphocyte doubling time and Pgp
      positivity was found in this series of patients. Poor correlation between assays
      might reflect a lack of sensitivity of the DNR uptake assay. Drug accumulation
      may be influenced by other cellular efflux pumps unrelated to Pgp, making the DNR
      assay non-specific.

PMID- 8866143
TI  - Retinal findings in adult leukaemia: correlation with leukocytosis.
AB  - The associations between retinal findings and haematological parameters in acute
      leukaemia are controversial. Sixty-three newly-diagnosed acute leukaemia
      patients, aged 12-77 years, were studied prospectively for the presence of intra
      retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton wool spots
      (CWS) and macular haemorrhages (MH), Thirty-three patients (52.4%) showed at
      least one retinal abnormality. The prevalence of individual findings was: IRH (30
      cases), WCH (20 cases), CWS (5 cases), MH (11 cases). In contrast to previous
      studies, there was no association between any of these retinal findings and the
      haemoglobin level or the platelet count. There was a higher median WBC in
      patients with IRH (68 x 10(9)/l) than in those without IRH (15.4 x 10(9)/l), P =
      0.037. When the acute myeloblastic leukaemia cases were considered separately, an
      association was also found between higher WBC and the presence of WCH and CWS.
      There was no association between retinal findings and FAB type in the AML cases.
      We conclude that a high WBC may be at least as important as anaemia and
      thrombocytopenia in the pathogenesis of the retinopathy of acute leukaemia.

PMID- 8866144
TI  - A semi-automated method for analysis of intron 13 and intron 22 dinucleotide
      repeat polymorphisms of the factor VIII gene.
AB  - A semi-automated method has been developed for the simultaneous analysis of two
      micro-satellite repeat polymorphisms located in intron 13 and 22 of the Factor
      VIII gene. The fluorescent dyes, 6-FAM-and HEX-phosphoramidites were used to 5'
      end label the respective 5' primers of these two microsatellite repeats and a
      multiplex polymerase chain reaction (PCR) devised for amplification. The PCR
      product was loaded onto the gel with DNA size marker labelled with ROX. A total
      of 24 samples could be analysed simultaneously on an automated DNA sequencer. The
      results were computed using a dedicated software, with assignment of PCR product
      size in basepair. This method compares well with the conventional manual
      procedure using radio-labelled primers, but at the same time overcomes many of
      the inherent disadvantages associated with the latter method.

PMID- 8866145
TI  - Hodgkin's disease after cardiac transplant: a report of two cases.
AB  - Non-Hodgkin's lymphoma is a well recognized sequela of transplant related
      immunosuppression. Hodgkin's disease has only rarely been described in this
      context. We describe two cases of Hodgkin's disease after heart and heart/lung
      transplants respectively. Both patients continued to receive immunosuppressive
      therapy with cyclosporin and prednisolone, and received combination chemotherapy.
      One died of Aspergillus infection following the second course of chemotherapy.
      The other patient completed his chemotherapy and remains in remission. We discuss
      the possible aetiology and management of post-transplant Hodgkin's disease.

PMID- 8866146
TI  - Constrictive pericarditis in B cell chronic lymphatic leukaemia.
AB  - We report a case of B-cell chronic lymphatic leukaemia (B-CLL) complicated by
      constrictive pericarditis. The pericardial involvement was confirmed
      histologically to be leukaemic in nature. We draw attention to this complication
      which is amenable to surgical correction. To our knowledge this has been
      described only once before as an autopsy finding and has not been encountered
      ante-mortem.

PMID- 8866148
TI  - Letter from America: how I learned to stop worrying and love CLIA.

PMID- 8866147
TI  - t(9;13)(q34;q12) chromosomal translocation persisting 4 years post autologous
      bone marrow transplantation for secondary AML despite morphological remission.
AB  - A 42-year-old male patient with a history of occupational exposure to benzene
      presented with pancytopenia. His bone marrow showed evidence of trilineage
      dysplasia and cytogenetic analysis revealed a unique t(9;13)(q34;q12)
      translocation. Five months after diagnosis he developed secondary AML. He was
      treated with four courses of chemotherapy and an autologous bone marrow
      transplantation (BMT). Four years post-transplantation he remains in
      haematological and morphological remission though the cytogenetic abnormality is
      still present in all metaphases examined.

PMID- 8866149
TI  - Chlorambucil and prednisolone therapy in a patient with T-cell chronic
      lymphocytic leukaemia.

PMID- 8866150
TI  - Cobalamin and folate deficiencies.

PMID- 8866151
TI  - Improved cell counting in osmotically resistant erythrocytes.

PMID- 8866152
TI  - Difficulty in applying discriminant function to patients with HbE trait.

PMID- 8866153
TI  - Sensitivity reaction to parenteral vitamin B12: recurrence of symptoms after
      Marmite ingestion.

PMID- 8866154
TI  - A note on specific counting of platelets using fluorescent antibodies.

PMID- 8866155
TI  - On rest and pain.

PMID- 8866156
TI  - Between the idea and the reality: research on bed rest for uncomplicated acute
      low back pain and implications for clinical practice patterns.

PMID- 8866157
TI  - The life you save may be your own.

PMID- 8866158
TI  - Spinal opioid infusions in the treatment of chronic pain of nonmalignant origin.
AB  - OBJECTIVE: To review the published literature on the use of spinal opioids in the
      treatment of chronic pain due to nonmalignant diseases. DESIGN: Literature
      review. RESULTS: Ten studies describing 146 patients have been located and
      reviewed. The data are insufficient to permit formal analysis. CONCLUSION: The
      proper role of intraspinal opioids in the treatment of chronic pain not due to
      cancer cannot be determined from the existing literature. Intraspinal opioids
      should be considered an experimental procedure for chronic pains not due to
      cancer until better data can be obtained; all patients who receive such therapy
      should be part of a clinical protocol whose results are published. The
      development of standardized clinical trial methodology and case reporting
      protocols would facilitate this process.

PMID- 8866159
TI  - A review of evidence about factors affecting quality of pain management in sickle
      cell disease.
AB  - OBJECTIVE: To assess the evidence for pharmacological, behavioural, and
      interpersonal influences on quality of pain management in sickle cell disease.
      DATA SOURCES: English-language reports from the research literature up to 1995,
      identified using Medline, Psychlit, and the Bath Information Data Service. STUDY
      SELECTION: Studies are reviewed that (a) reported quantitative clinical outcomes
      for particular analgesic methods used to treat painful episodes or (b) provide
      data on patient factors, interpersonal treatment factors, or levels of drug
      dependence in relation to pain management in sickle cell disease. DATA SYNTHESIS:
      Findings vary on the effectiveness of longer-acting opiates, patient-controlled
      or continuously infused analgesia, and behavioural analgesic techniques, with
      better results for trials where interpersonal aspects of pain management were
      also addressed. Risks for poorer pain management are greatest for patients in
      adverse social circumstances, who are more severely affected by painful episodes
      and who are poorly adjusted and have less effective personal strategies for
      coping with pain, but the limited evidence on drug dependence indicates very low
      levels by comparison with risk and exposure factors. CONCLUSIONS: Analgesic
      methods and approaches should continue to be developed and evaluated, but
      conflicting perceptions between patients and staff about pain that is reported
      and analgesia that is required probably contribute most to poor pain management
      in sickle cell disease. Promising areas for future research include the
      assessment of patients' everyday pain coping styles and patterns of drug use in
      relation to their hospital experiences of pain management, and the evaluation of
      psychological interventions to improve patients' styles and strategies for coping
      with pain.

PMID- 8866160
TI  - Relationship of subjective disability with pain intensity, pain duration, pain
      location, and work-related factors in nonoperated patients with chronic low back
      pain.
AB  - OBJECTIVE: A cross-sectional study on patients with chronic low back pain to
      compare relationships between subjective disability and pain intensity, pain
      duration, pain location, and work-related factors. DESIGN AND SUBJECTS: One
      hundred and seven outpatients with low back pain, with or without radiation to
      the legs, of at least 3 months' duration, were administered a comprehensive back
      patient questionnaire. The questionnaire included the Pain Disability Index (PDI)
      for the assessment of overall perceived disability and assessments of pain
      intensity, duration, and location and two pretested short-form work
      questionnaires. None of the patients had undergone a back operation. SETTING:
      Tertiary care center. RESULTS: There was evidence of significant
      interrelationships between the PDI and pain intensity (low back pain, r = 0.53, p
      < 0.001; leg pain, r = 0.32, p < 0.01; and buttock pain, r = 0.36, p < 0.01),
      pain location (significantly higher scores with distal pain radiation), and work
      related factors (a work load sum score of r = 0.31, p < 0.01; significantly
      higher scores in patients on sick leave). CONCLUSIONS: The results suggest that
      subjective disability in patients with chronic low back pain overlaps with both
      pain and work-related factors. The observations support the multidimensionality
      of low back disability.

PMID- 8866161
TI  - Transcutaneous electrical nerve stimulation (TENS) treatment outcome in long-term
      users.
AB  - OBJECTIVE: Previous reviewers of the literature on transcutaneous electrical
      nerve stimulation (TENS) outcome have concluded the following: (a) there are few
      long-term TENS follow-up studies, and (b) fewer studies have addressed the effect
      of long-term TENS use on outcome variables other than pain (e.g., function).
      DESIGN/SETTING/PARTICIPANTS/OUTCOME MEASURES: From a population of 2,003 chronic
      pain patients (CPPs) who bought a TENS device for pain management, 506 patients
      were randomly selected and interviewed by telephone long enough after purchase to
      allow at least 6 months of TENS use. The interview process used a structured
      "skip" questionnaire designed to assess the CPPs' perceptions regarding the
      effectiveness of TENS for a variety of outcome variables. Of the 506 CPPs
      interviewed, 376 (74.3%) had used their TENS device for 6 months or longer and
      were defined as long-term users. The responses of this group of CPPs to the
      telephone questionnaire were then subjected to statistical analysis. RESULTS:
      Paired t-tests, correlated z-tests, SS Wilks, and chi-square tests demonstrated
      statistically significant change or improvement (p < 0.05) that paralleled the
      introduction of TENS use in the following outcome variables: less pain
      interference with work, home, and social activities; increased activity level and
      pain management; decreased use of other therapies (e.g., physical therapy,
      occupational therapy, chiropractic); decreased use of narcotics, tranquilizers,
      muscle relaxants, nonsteroidal anti-inflammatory drugs and steroids. CONCLUSIONS:
      The results suggest that TENS is associated with improvement on multiple outcome
      variables in addition to pain relief for CPPs who are long-term users. Also, for
      some CPPs, long-term TENS use continues to be effective.

PMID- 8866162
TI  - Sexual abuse and chronic musculoskeletal pain: prevalence and psychological
      factors.
AB  - OBJECTIVE: We investigated the prevalence of a history of sexual abuse among
      patients with long-term musculoskeletal pain. Psychological factors associated
      with abuse and pain were also studied. DESIGN: First, the prevalence of abuse was
      determined based on self-report on a valid and reliable abuse questionnaire.
      Subsequently, a cross-sectional method, in which patients were categorized as
      abused or nonabused, was employed and responses to a battery of questionnaires
      compared. PATIENTS: Seventy-five consecutive patients undergoing assessment for
      chronic musculoskeletal pain participated. OUTCOME MEASURES: These included
      Beck's Depression Inventory, the Coping Strategies Questionnaire, the
      Multidimensional Pain Inventory, the Uppsala Type A Behavior Questionnaire, the
      Pain and Impairment Rating Scale, as well as ratings of pain intensity. RESULTS:
      Thirty-eight percent of the women and 10% of the men reported some form of sexual
      abuse, usually during adulthood. A majority (77%) had disclosed the abuse to
      someone, but >85% did not believe that the abuse negatively affected their pain
      or sex lives. Abused women, relative to nonabused ones, had poorer scores on 27
      of the 29 assessment variables. Abused female patients had significantly higher
      levels of depression, stress from daily hassles, affective distress, and more
      frequent negative responses from spouses, in addition to having lower levels of
      social activities, life control and effective coping for pain than did the
      nonabused female patients. CONCLUSION: These data extend the relationship between
      sexual abuse and pain to a Swedish population suffering from musculoskeletal
      complaints. Our findings suggest that intervention in the pain treatment setting
      may need to address further the problems of effective coping strategies and
      depression.

PMID- 8866163
TI  - Innervation of hyperalgesic skin in patients with complex regional pain syndrome.
AB  - OBJECTIVE: To look for anatomical and histochemical signs of interaction between
      sensory and sympathetic nerves in the hyperalgesic skin of patients with complex
      regional pain syndrome. SUBJECTS: Skin samples were obtained from eight patients
      whose condition developed after a suspected or confirmed peripheral nerve injury,
      and from nine patients with features of reflex sympathetic dystrophy (RSD)
      following a soft-tissue injury. A skin sample was also obtained from 18 control
      subjects of similar age and sex distribution to patients. DESIGN: In patients,
      skin samples were taken from an area of static mechanical hyperalgesia and from
      an equivalent site in the contralateral limb. In controls, skin samples were
      obtained from the dorsum of one hand or foot. HISTOCHEMICAL MARKERS: We used
      neuron-specific enolase for all classes of nerve fiber; tyrosine hydroxylase for
      noradrenergic fibers; vasoactive intestinal peptide for sympathetic sudomotor
      fibers; tyrosine hydroxylase co-existing with neuropeptide Y for sympathetic
      vasoconstrictor fibers; and calcitonin gene-related peptide with substance P or
      somatostatin for peptide-containing unmyelinated sensory fibers. RESULTS: In
      patients, the distribution of markers was similar in skin taken from an area of
      mechanical hyperalgesia and skin taken from an equivalent site contralaterally,
      and was unrelated to clinical features of RSD. The distribution of markers did
      not differ between patients and controls. Nerve tangles immunoreactive to neuron
      specific enolase, but not to other markers, were detected in samples taken from
      four patients and two controls. The nerve tangles were present bilaterally in two
      patients, and only on the affected side in two other patients. The clinical
      condition was more fully developed in the four patients whose skin samples
      contained nerve tangles than in most other patients. CONCLUSIONS: A major
      difference in distribution or change in histochemical content of cutaneous
      autonomic or nociceptor fibers is unlikely to underly static mechanical
      hyperalgesia following a soft-tissue or peripheral nerve injury. The relevance of
      cutaneous nerve tangles for the pathophysiology of RSD is uncertain.

PMID- 8866164
TI  - Social barriers to optimal pain management in infants and children.
AB  - OBJECTIVE: To examine the social barriers that lead to less than optimal
      management of pain in children. DESIGN: Recognizing the vulnerabilities of
      infants and children and their dependence on caring adults, a model of pain
      communication is proposed. The model examines (a) the pain experiences of
      children, including social determinants; (b) developmental variations in the
      capacity to encode the severity and qualities of pain as expressive behavior; (c)
      adult skills and deficiencies in decoding pain; and (d) the actions of adults
      predicated on the meaning and significance attached to children's actions.
      Limitations in care were examined. DATA SOURCES: The current research and
      professional literature were accessed through searches of the Psyclit and Medline
      databases for relevant investigations on the basis of our working knowledge of
      the literature. CONCLUSION: Numerous deterrents to optimal care are identified in
      the domains of commonplace beliefs about the nature of pain in infants and
      children: failure to recognize the impact of socialization in familial and
      cultural modes of experience and expression; needs for age-specific assessment
      instruments; the limited capacity to use available evidence concerning pain; the
      need to employ clinicians, parents, and other adults more effectively in
      delivering care; and structural problems in the health care system.

PMID- 8866166
TI  - Chronic pain.

PMID- 8866165
TI  - Effective but near disastrous subarachnoid neurolysis for mechanical root pain in
      a paraplegic cancer patient.
AB  - CASE REPORT: A 43-year-old white man with advanced renal cell carcinoma and
      consequent paraplegia complained of the new onset of lancinating pain involving
      the right upper chest wall. This pain, which was superimposed on well-controlled
      chronic back pain and was intermittent and related to activity, failed to respond
      to conventional pharmacologic management. METHODS AND RESULTS: A cisternal
      myelogram suggested an absence of gross rostral extension of spinal metastases,
      and subarachnoid neurolysis was performed with hyperbaric phenol. Unexpected
      contralateral brachial weakness developed towards the conclusion of the
      procedure, but resolved spontaneously. The target pain had not recurred at follow
      up 8 months later.

PMID- 8866167
TI  - R-albuterol. Preclinical and clinical pharmacology of R-albuterol. From molecule
      to man.

PMID- 8866168
TI  - Concerns regarding the current use of beta-agonists in the therapy of asthma.

PMID- 8866169
TI  - Albuterol. A pharmaceutical chemistry review of R-, S-, and RS-albuterol.

PMID- 8866170
TI  - Comparison of R-, S-, and RS-albuterol interaction with human beta 1- and beta 2
      adrenergic receptors.

PMID- 8866171
TI  - S-albuterol exacerbates calcium responses to carbachol in airway smooth muscle
      cells.

PMID- 8866172
TI  - Effects of albuterol enantiomers on in vitro bronchial reactivity.

PMID- 8866173
TI  - Anomalous effects of albuterol and other sympathomimetics in the guinea pig.

PMID- 8866174
TI  - Effects of RS-albuterol on the development of antigen-mediated airway
      hyperreactivity in guinea pigs.

PMID- 8866175
TI  - Stereoselective metabolism of RS-albuterol in humans.

PMID- 8866177
TI  - Differential responses of asthmatic airways to enantiomers of albuterol.
      Implications for clinical treatment of asthma.

PMID- 8866178
TI  - The mycobacteriology laboratory. Past, present, and future.
AB  - The role of the mycobacteriology laboratory in tuberculosis control programs has
      been underestimated in the past, but now laboratory services are proven to play
      an essential role if properly implemented. The importance and reliability of
      these services in the future will depend on their centralization in specialized
      mycobacteriology laboratories that will be able to put new technologies into
      practice. The shortest turnaround time and the greatest cost effectiveness can be
      achieved by direct submission of raw specimens to such laboratories, especially
      for the management of new tuberculosis patients.

PMID- 8866176
TI  - Enantioselective disposition of albuterol in humans.
AB  - The study of enantioselective disposition of chiral drugs is important to provide
      a rationale of plasma concentration-effect relationships, which are often
      misleading when based on total drug concentration. It is also important when
      considering new dosage routes or formulations in order to optimize therapeutic
      plasma concentrations of the active enantiomer. Improvements in the sensitivity
      and selectivity of biological assays coupled with the developments in chiral
      analysis have made it possible to study the enantioselective disposition of
      drugs. Although valuable pharmacokinetic data were obtained for the beta 2
      agonists by nonenantioselective methodology, more recent chiral studies have
      revealed the existence of extensive enantioselectivity in the disposition of
      these agents. The most significant features of the enantioselective disposition
      of albuterol are the relatively rapid plasma clearance and low bioavailability of
      the eutomer. Although this in itself does not necessarily justify the development
      of a single enantiomer formulation, the implications of the high levels of
      distomer after i.v. and oral dosing await clarification. Similarly, more work is
      required to elucidate the consequences of the major difference in disposition
      between albuterol and terbutaline in humans through both in vivo and in vitro
      studies of the mechanisms giving rise to this phenomenon. The enantioselective
      disposition of the other clinically used beta 2-agonists, such as fenoterol,
      formoterol, and salmeterol also needs to be characterized. The metabolism of the
      majority of beta 2-agonists is generally by conjugation to give one major
      metabolite. The situation is therefore uncomplicated by multiple metabolic
      pathways, which may differ in the extent and direction of their
      enantioselectivity. Many beta 2-agonists are excreted largely unchanged in the
      urine making studies of urinary excretion accessible without the requirement for
      very sensitive assays. The realization that the enantiomers of beta 2-agonists
      previously thought of as "inactive" may be associated with toxic effects is a
      further compelling reason to study the enantioselective pharmacokinetics of this
      class of drugs. In addition, the role of enantiomers in producing side effects,
      such as tremor and reduction in renal function, needs to be reassessed. The beta
      2-agonists can be looked on as textbook examples of the inherent danger of
      ignoring chirality in the study of pharmacokinetics and pharmacodynamics. The
      growing body of information on the enantioselective disposition of beta 2
      agonists in humans will enhance the rational use of these drugs in the future
      management of patients.

PMID- 8866179
TI  - Biosafety in the clinical mycobacteriology laboratory.
AB  - This article presents an expanded agent summary statement for laboratorians
      working with Mycobacterium tuberculosis. It focuses on reducing the serious risk
      of infection in clinical laboratories that process specimens from tuberculosis
      patients or that work with purified cultures of tubercle bacilli. Administrative
      and engineering controls, practices and procedures, and personal protective
      equipment are discussed. Guidelines for packaging specimens for transfer to
      another laboratory also are presented.

PMID- 8866180
TI  - Primary processing of specimens and isolation and cultivation of mycobacteria.
AB  - Processing of specimens for mycobacteria need to proceed as rapidly as possible
      to provide 24 hour turnaround for smears and 21-day turnaround for the
      identification of Mycobacterium tuberculosis. If these goals are to be
      accomplished, a broth culture or microcolony plate method must be part of the
      media and in the planting process. Use of conventional solid media alone does not
      provide adequate turnaround time.

PMID- 8866181
TI  - Identification of mycobacteria by conventional methods.
AB  - The methodology and use of the conventional tests employed in the identification
      of the currently recognized human mycobacterial pathogens are reviewed. The
      common disease presentations of each species are briefly noted. Tabular summaries
      of the phenotypic characteristics of these organisms have also been provided. It
      should be re-emphasized that the use of conventional methods, unlike the rapid
      methods now available, is not recommended for the initial identification of the
      M. tuberculosis complex. We also urge caution in the identification of unfamiliar
      or atypical isolates. It is to be expected that additional species of human
      mycobacterial pathogens will be characterized in the future; many of these may be
      represented by isolates that differ phenotypically little, if at all, from
      species currently recognized.

PMID- 8866182
TI  - Methods for the rapid identification of mycobacterial species.
AB  - The use of rapid tests for the identification of mycobacteria has been advocated
      primarily for Mycobacterium tuberculosis; however, they have been accepted less
      widely than expected. Chromatographic methods are best suited for larger
      laboratories, whereas nucleic acid probes may be used by laboratories that can
      justify the cost based on volume and pricing. Nucleic acid sequencing offers the
      possibility of providing the most exact identification of species of
      mycobacteria, but its use is limited to reference laboratories that have the
      applicable resources. Because of their clinical importance, all mycobacteria
      should be identified using the most rapid methods available.

PMID- 8866183
TI  - Polymerase chain reaction and other amplification techniques in mycobacteriology.
AB  - Amplification methods for detection of Mycobacterium tuberculosis, such as
      polymerase chain reaction (PCR), have undergone much research and development in
      the last several years. The most common methods for extraction, amplification,
      and detection of mycobacterial nucleic acid sequences used in "in-house" PCR
      assays are discussed. A list of commercially prepared PCR and non-PCR
      amplification assays that should be available soon is included. The pros and cons
      of "in-house" versus commercial technology and issues of implementation of
      molecular technology in the clinical laboratory are reviewed.

PMID- 8866184
TI  - Clinical mycobacteriology. Drug susceptibility testing.
AB  - An update on drug susceptibility testing is provided on methods for testing
      Mycobacteria tuberculosis, Mycobacteria avium, and rapidly growing mycobacteria.
      Emphasis is placed on the techniques that are currently available in clinical
      laboratories, and a critical overview is offered for some methods undergoing
      development.

PMID- 8866185
TI  - Quality assurance in the mycobacteriology laboratory. Quality control, quality
      improvement, and proficiency testing.
AB  - In conclusion, the components of QA (QC, QI, and PT) in the mycobacteriology
      laboratory address not only the accuracy of testing but also provide a measure
      for the laboratory practices that are necessary to effectively diagnose and
      control tuberculosis in the community. Given the extremely important role of
      laboratory testing in the control of tuberculosis, providing rapid diagnosis and
      determination of susceptibility test results, laboratories should use the
      recommendations concerning turnaround times as either achievable goals or a
      measure of whether the laboratory should be performing mycobacteriology tests. We
      strongly urge laboratories to include their turnaround times for test results and
      the timeliness of reporting those results in their annual QA program.

PMID- 8866186
TI  - Clinical mycobacteriology. Work flow and optional protocols for laboratories in
      industrialized countries.
AB  - The algorithm of the mycobacteriology laboratory of the 1990s relies heavily on
      growth-dependent procedures that are slow and labor intensive. The introduction
      of nucleic acid-based direct amplification tests portends future laboratories
      where molecular diagnostic assays will prevail. Financial constraints mandate an
      interdisciplinary approach to establish clinical pathways and rational tailoring
      of current protocols to curtail expensive overuse of dwindling resources.

PMID- 8866187
TI  - Tuberculosis bacteriology laboratory services and incremental protocols for
      developing countries.
AB  - Tuberculosis causes more deaths worldwide than any other single infectious
      disease. Most new cases occur in developing countries, where the emergence of
      HIV/AIDS-associated multidrug-resistant Mycobacterium tuberculosis could disrupt
      the effective delivery of chemotherapy. Diagnosis, one of the cornerstones of the
      modern national tuberculosis control programs in developing countries, is based
      on sputum smear microscopy, which can be delivered effectively only through a
      national laboratory network. Tuberculosis diagnostic services can be delivered in
      lock step with the expanding laboratory network in an incremental manner,
      beginning with the simplest procedure and ending with the most sophisticated
      ones.

PMID- 8866188
TI  - Therapeutic drug monitoring of the antimycobacterial drugs.
AB  - Because MDR tuberculosis and MAC are difficult to treat, TDM with the
      antimycobacterial drugs has become the standard of practice at NJC. By combining
      specific and sensitive assays, carefully collected samples, and clinical
      expertise, we are able to control and optimize antimycobacterial drug therapy. We
      continue to refine our approach with ongoing pharmacokinetic and pharmacodynamic
      research. Although such an array of services is not typical of most
      nonspecialized institutions, it is possible to follow the techniques described
      and to access our assay services. Furthermore, the elements of a good TDM service
      described can be applied to the TDM for any other disease state.

PMID- 8866189
TI  - Clinical mycobacteriology. Activities and recommendations by the association of
      state and territorial public health laboratory directors.
AB  - By using the assessment, policy development, and assurance model to describe the
      functions of public health, the Association of State and Territorial Public
      Health Laboratory Directors (ASTPHLD) is shown to be responding to the laboratory
      aspects of tuberculosis detection, prevention, and control. The many activities
      described illustrate the value of public-private partnerships in addressing
      population-based, public health threats. The network of state and territorial
      public health laboratories, through voluntary involvement in ASTPHLD, provides an
      important resource to the scientific, educational, and policy-making community.

PMID- 8866190
TI  - Managing physician use of laboratory tests.
AB  - The active management of laboratory test utilization appears to be a practical
      approach to addressing the financial pressures imposed by managed care and
      capitated reimbursement, and can complement efforts already underway in most
      laboratories to reduce the unit cost of testing. Managing laboratory utilization
      takes time that is often in short supply; however, the literature suggests that
      the savings from a well-focused effort can easily exceed the costs of a
      utilization management program. Individuals and institutions that commit
      themselves to active utilization management need to realize (1) how laboratory
      utilization is measured, (2) benchmarks within the industry, and (3) the stubborn
      structural and psychological constraints that are likely to limit progress. Some
      approaches to reducing utilization, such as education, have poor track records
      and are best avoided. Other avenues, such as providing financial feedback and
      making specific changes to the environment in which tests are ordered, have
      demonstrated moderate success in the past and hold considerably more promise.

PMID- 8866191
TI  - Sibling rivalry in the 1990s.

PMID- 8866192
TI  - The "lupus" circulating anticoagulant, AKA the primary antiphospholipid syndrome.

PMID- 8866193
TI  - Domestic violence: identification and management for the clinician.

PMID- 8866194
TI  - Comprehensive management of atopic dermatitis.

PMID- 8866195
TI  - Helicobacter pylori and peptic ulcer disease: issues for primary care providers.

PMID- 8866197
TI  - The management of prostate cancer in blacks: the physician's dilemma intensified.

PMID- 8866196
TI  - Adult immunizations.

PMID- 8866198
TI  - Results of randomized clinical trials of magnesium--can a consensus be reached?

PMID- 8866199
TI  - Review of research methodology used in clinical trials of magnesium and
      myocardial infarction--why does controversy persist despite ISIS-4?

PMID- 8866200
TI  - Review of clinical evidence--is there a role for supplemental magnesium in acute
      myocardial infarction in high-risk populations (patients ineligible for
      thrombolysis and the elderly)?

PMID- 8866201
TI  - Magnesium and arrhythmias in acute myocardial infarction.

PMID- 8866202
TI  - How magnesium therapy may influence clinical outcome in acute myocardial
      infarction: review of potential mechanisms.

PMID- 8866203
TI  - Angiotensin converting enzyme polymorphism is associated with severity of
      coronary heart disease and serum lipids (total cholesterol and triglycerides
      levels) in Japanese patients.
AB  - BACKGROUND: Much past research has concerned the relationship between coronary
      heart disease and the angiotensin converting enzyme (ACE) genotype, with many
      lines of evidence demonstrating polymorphism to be an independent risk factor for
      myocardial infarction. Interestingly, however, association of ACE polymorphism
      and severity of coronary artery stenosis according to racial background has
      recently been proposed. OBJECTIVE: To clarify the relationship between the ACE
      genotype and severity of coronary artery stenosis in Japanese patients. METHODS:
      In 36 consecutive patients undergoing coronary catheterization, comparative
      examination of coronary angiography findings with the ACE genotype was conducted.
      RESULTS: The severity of coronary artery stenosis indeed showed a relationship
      with the ACE genotype, with more severe coronary artery stenosis associated with
      the deletion (D) allele (P < 0.05). The serum lipids, total cholesterol and
      triglycerides levels, were also elevated in patients with the D allele (P <
      0.05). CONCLUSION: We have provided further evidence that ACE polymorphism is
      associated with severity of coronary heart disease in a Japanese population. A
      possible relationship between serum lipids and the ACE genotype is also
      suggested.

PMID- 8866204
TI  - Prolonged streptokinase infusion in patients with unstable angina: results of a
      randomized, placebo-controlled clinical trial.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy both of
      prolonged (48 h) and of short-duration (1 h) administrations of streptokinase in
      patients with unstable angina. In unstable angina, thrombosis is a dynamic
      process that waxes and wanes for hours and even days. The majority of previous
      studies have investigated the efficacy of short-duration thrombolytic regimens.
      METHODS: One hundred patients with acute unstable angina were randomly allocated
      to receive placebo, 1,500,000 U streptokinase during 1 h or 250,000 U
      streptokinase during 1 h and then a prolonged infusion of 100,000 U for the next
      48 h. All of the treatments included intravenous heparin administration for 72 h.
      RESULTS: No death occurred in the study population. One of 34 patients treated
      with placebo (2.9%), three of 33 treated with streptokinase during 1 h (9.0%) and
      three of 33 treated with streptokinase during 48 h (9.0%) had a myocardial
      infarction. Refractory angina occurred in nine, three and seven patients
      receiving placebo, streptokinase during 1 h and streptokinase during 48 h,
      respectively. Kaplan-Meier analysis showed that the total probability for a
      patient to be free of cumulative events did not differ among the three groups of
      patients (NS). Fourteen patients (41%) receiving placebo, 15 patients (45%)
      receiving streptokinase during 1 h and 14 patients (42%) receiving streptokinase
      during 48 h had ischaemic episodes detected by Holter monitoring during the first
      72 h after hospital admission (NS). Two patients receiving streptokinase during
      48 h required blood transfusion, and a greater incidence of minor bleeding (P <
      0.05) and adverse events (P < 0.02) was observed in patients receiving prolonged
      streptokinase administration than in those receiving streptokinase during 1 h or
      placebo. CONCLUSIONS: In patients with acute unstable angina, the administration
      of two different regimens of streptokinase significantly reduces the probability
      neither of developing cardiac events during hospitalization nor of ischaemia
      detected by Holter monitoring in the early phase after hospital admission.
      Although the sample size of the study provided sufficient power to exclude only a
      large difference in effect size, it did allow us to detect a significantly higher
      incidence of bleeding in the group of patients treated with prolonged
      streptokinase infusion.

PMID- 8866206
TI  - Bibliography current world literature.

PMID- 8866205
TI  - Relation of electron beam computed tomography screening for coronary calcium to
      cardiovascular risk and disease: a review.
AB  - Electron beam computed tomography has become an increasingly popular technology
      to noninvasively screen for coronary artery calcium as a marker of
      atherosclerotic burden. Coronary artery calcium is invariably associated with
      atherosclerosis, and the amount (volume, mass, or calculated 'score') of calcium
      is directly associated with age, male gender, and other cardiovascular risk
      factors. Coronary artery calcium is highly sensitive and moderately specific for
      the identification of angiographically significant disease. Recent reports also
      show a direct association between the amount of coronary calcium and the risk of
      combined new coronary events and revascularization in previously asymptomatic
      individuals, and hard coronary events among symptomatic patients. Coronary artery
      screening by electron beam computed tomography is a cost-effective tool compared
      with other diagnostic modalities when the pre-test likelihood of disease is low
      to moderate. Although some reports have shown significant retest variability in
      calcium scores obtained from repeated scans, and in the individual relationship
      between angiographic disease and coronary calcium quantity, such variability may
      be minimized by averaging results from two or more consecutive scans, techniques
      to minimize respiratory motion artifact, and possibly the use of thicker scan
      slice thicknesses. Serial scanning by electron beam computed tomography is also
      being investigated as a noninvasive tool for following the effects of medical or
      lifestyle intervention for controlling cardiovascular risk factors or disease. At
      present, coronary artery scanning by electron beam computed tomography may be
      most appropriately utilized in screen patients with established coronary risk
      factors or known or suspected coronary disease, and in combination with
      established diagnostic testing to confirm the presence of suspected coronary
      disease.

PMID- 8866207
TI  - Appropriate diagnostic evaluation.

PMID- 8866208
TI  - Stage-directed treatment guidelines.

PMID- 8866209
TI  - Surgical approaches in special situations.

PMID- 8866210
TI  - Locally advanced non-small cell lung cancer: the "local" issue.

PMID- 8866211
TI  - Malignant pleural effusions.

PMID- 8866212
TI  - Orthopedic implants: a guide to radiographic analysis.
AB  - Orthopedic technology is growing at a rapid rate. New implants reflect this
      technology whether it pertains to fracture fixation, joint replacement, spine
      stabilization, or soft-tissue reconstruction. This monograph is designed to
      assist both the radiologist and the orthopedist in accurately assessing plain
      radiographs of commonly used orthopedic implants. We discuss the biologic
      response of the surrounding bone to these devices; herein lies the key to
      understanding the radiographic presentation of these devices.

PMID- 8866213
TI  - Lyme disease.

PMID- 8866214
TI  - A history of the International Society for Analytical Cytology.

PMID- 8866216
TI  - Enzyme-generated intracellular fluorescence for single-cell reporter gene
      analysis utilizing Escherichia coli beta-glucuronidase.
AB  - We report the development of a new fluorescence-activated cell sorter (FACS)
      based reporter gene system utilizing the enzymatic activity of the E. coli beta
      glucuronidase (gus) gene. When loaded with the Gus substrate fluorescein-di-beta
      D-glucuronide (FDGlcu), individual mammalian cells expressing and translating gus
      mRNA liberate sufficient levels of intracellular fluorescein for quantitative
      analysis by flow cytometry. This assay can be used to FACS sort viable cells
      based on Gus enzymatic activity, and the efficacy of the assay can be measured
      independently by using a fluorometric lysate assay. Furthermore, both the beta
      glucuronidase and the previously described E. coli beta-galactosidase enzymes
      have high specificities for their cognate substrates, allowing each reporter gene
      to be measured by FACS independently.

PMID- 8866217
TI  - Automated particle classification based on digital acquisition and analysis of
      flow cytometric pulse waveforms.
AB  - In flow cytometry, the typical use of front-end analog processing limits the
      pulse waveform features that can be measured to pulse integral, height, and
      width. Direct digitizing of the waveforms provides a means for the extraction of
      additional features, for example, pulse skewness and kurtosis, and Fourier
      properties. In this work, we have first demonstrated that the Fourier properties
      of the pulse can be employed usefully for discrimination between different types
      of cells that otherwise cannot be classified by using only time-domain features
      of the pulse. We then implemented and evaluated automatic procedures for cell
      classification based on neural networks. We established that neural networks
      could provide an efficient means of classification of cell types without the need
      for user interaction. The neural networks were also employed in an innovative
      manner for analysis of the digital flow cytometric data without feature
      extraction. The performance of the neural networks was compared with that of a
      more conventional means of classification, the K-means clustering algorithm.
      Neural networks can be realized in hardware, and this, in addition to their
      highly parallel architecture, makes them an important potential part of real-time
      analysis systems. These results are discussed in terms of the design of a real
      time digital data acquisition system for flow cytometry.

PMID- 8866215
TI  - Evaluation of a time-resolved fluorescence microscope using a phosphorescent Pt
      porphine model system.
AB  - A time-resolved fluorescence microscope is presented that allows the sensitive
      detection of delayed luminescent labels with decay times from one microsecond to
      several milliseconds. The microscope utilizes an argon ion laser chopped with an
      acoustooptical modulator as excitation light source in combination with a gated
      multichannel plate image intensifier in the image plane. A theoretical model for
      the detection efficiency of practically any time-resolved fluorescence microscope
      is verified using phosphorescent Pt-porphine-stained Sephadex beads. The
      detection efficiency of the presented setup was shown to be 42%, which is near
      the theoretical limit of 50% for non-saturated luminescent dyes. The suppression
      of prompt fluorescence signals was found to be 1:5,500. The Pt-porphine beads
      proved to be an excellent model system for time-resolved fluorescence microscopy,
      showing a high extinction coefficient and high phosphorescence quantum yield in
      aqueous environment under room temperature conditions. Furthermore, for the
      microscope described the decay time of the Pt-porphine beads of 47 microseconds
      is long enough to enable efficient suppression of the prompt fluorescence while
      maintaining a high excitation and emission duty cycle. This is considered to be
      of vital importance in order not to saturate the luminescence with the excitation
      intensities commonly used in fluorescence microscopy.

PMID- 8866218
TI  - Hollow-fibre affinity cell separation system for CD34+ cell enrichment.
AB  - A hollow-fibre immunoadsorption system has been developed for the purification of
      CD34+ cells from mononuclear cells. This cell separation technique is based on
      the use of uniform surface fluid shear stress to fractionate cells that attach to
      the inside surface of hollow fibres. Monoclonal antibody to the CD34 antigen was
      covalently coupled to the lumenal surface of cuprophan minidialysers (surface
      area 220 cm2). After the selective adsorption of CD34+ cells (28 min), a depleted
      fraction was collected at 5 dynes/cm2 followed by washes at 10 and 25 dynes/cm2.
      Antigen-positive cells were recovered after incubation with chymopapain. The
      device was tested by using peripheral blood mononuclear cells from seven patients
      who had received granulocyte colony-stimulating factor and chemotherapy. The
      average number of cells processed was 1.3 +/- 0.2 x 10(8) (+/- S.E.M.), and the
      preselection incidence of CD34+ cells ws 1.6 +/- 0.6% (range 0.21-4.13%; n = 7).
      The enrichment purity was 94.4 +/- 3.1%, and 61 +/- 9% of input CD34+ cells were
      recovered in the enriched fraction (n = 4). Enrichment resulted in a 3.3 +/- 0.1%
      log10 depletion of CD34- cells (n = 4). Hollow-fibre affinity cell separation has
      potential as a medium to large-scale cell enrichment technology.

PMID- 8866219
TI  - Flow cytometric analysis of nuclear matrix proteins: method and potential
      applications.
AB  - The nuclear matrix (NM) is an important structural component of the nucleus that
      participates in the regulation of several diverse metabolic processes.
      Immunometric assays have shown that alterations in NM-associated functions and
      morphological characteristics may occur as a result of changes in NM composition.
      Recent evidence suggests that detection of quantitative or qualitative changes in
      nuclear matrix protein (NMP) composition may be useful in the diagnosis of cancer
      and as a reliable indicator of cell death. We have developed an in situ flow
      cytometric technique for the simultaneous detection of specific NMPs and DNA
      content in fixed, permeabilized cells. Illustrative results from two different
      applications of these methods involving two different cell lines (human melanoma
      and promyelocytic leukemia) are presented, including: 1) measurements of NM
      breakdown in necrotic and apoptotic cells after treatment with the cytotoxic
      agents camptothecin, etoposide, or hyperthermia; and 2) detection of changes in
      NMP content immediately after heat shock. We demonstrate that the technique is
      useful for the identification of cell-cycle specificity of NM breakdown and
      allows correlations to be made between the kinetics of DNA fragmentation and NMP
      solubilization. Furthermore, our studies indicate that flow cytometric detection
      of changes in NM composition may be useful for identifying different modes and
      temporal patterns of cell death. We discuss other potential applications of the
      technique and advantages over standard biochemical assays.

PMID- 8866220
TI  - Flow cytometric calibration of intracellular pH measurements in viable cells
      using mixtures of weak acids and bases.
AB  - We describe a new method for calibrating intracellular pH (pH1) measurements by
      flow cytometry, based on the null point method proposed originally by Eisner et
      al. (Pflugers Arch 413:553-558, 1989). The method involves suspending cells
      loaded with pH-sensitive dyes, such as SNARF-1 or BCECF, in defined mixtures of
      the weak acid butyric acid and the weak base trimethylamine. Only the uncharged
      forms of these agents freely permeate the plasma membrane. The weak acid donates
      protons intracellularly, whereas the weak base accepts them. In accordance with
      the Henderson-Hasselbalch equation, when cells are exposed to these mixtures, the
      steady-state pHi is displaced, and the fluorescence signal reflects this new pHi.
      The null point method described by Eisner et al. derives pHi by determining the
      molar ratio of acid to base that produces no change in fluorescence signal. In
      this paper, we show that it is not necessary to obtain the true null point,
      because a calibration curve can be derived from "pseudo null" values whose pHi is
      defined by the equation pHi = pHe -0.5 log [(AT)/(BT)], where pHe is the
      extracellular pH, and (AT) and (BT) are the total concentrations of weak acid and
      base in the suspension. We refer to this as the "pseudo null calibration method."
      It is rapid, technically simple, and reproducible. Compared with the widely used
      nigericin calibration method, it is not influenced by the intracellular potassium
      concentration; therefore, it may give a more reliable estimate of the absolute
      value of pHi.

PMID- 8866221
TI  - Use of four-colour flow cytometry to evaluate conjugate formation between human
      peripheral blood mononuclear cells and tumour target cells.
AB  - A four-colour flow cytometry technique is described for the determination of the
      number and phenotype of conjugate-forming mononuclear effector cells from human
      blood. The discriminatory power of previously described techniques was improved
      by labelling the effector cells with antibodies that simultaneously identified
      natural killer (NK), T, and myeloid cells and by labelling the tumour target
      cells with fluorescein octadecyl ester (FOE), so that cell conjugates could be
      differentiated from nonbinding effector cells more effectively than by the use of
      light scatter. The simultaneous characterisation of the three classes of
      conjugate-forming cells within a heterogeneous human peripheral blood mononuclear
      cell (PBMC) population made it possible to investigate conjugate formation by
      each subpopulation without purification, or semipurification (e.g., by monocyte
      removal), of the subpopulations. The binding of PBMCs to K562 and RPMI 1788
      targets was examined. Binding for all three PBMC subpopulations was optimal at 37
      degrees C and was negligible at 0 degree C (except for some T cell binding to
      RPMI 1788 cells). At 37 degrees C, maximum binding was essentially achieved by 10
      min. Sodium azide inhibited the majority of the conjugation by NK and T cells,
      and that inhibition could be removed by washing the cells prior to conjugation,
      whereas azide had a negligible effect on the binding by monocytes. It appears
      that effective conjugation by human peripheral blood NK and T lymphocytes
      requires the operation of an energy-dependent process, differentiating it from
      conjugation by monocytes.

PMID- 8866222
TI  - Flow cytometric detection and quantitative analysis of the GM-CSF receptor in
      human granulocytes and comparison with the radioligand binding assay.
AB  - A flow cytometric method to quantify the Granulocyte-macrophage colony
      stimulating factor receptor (GM-CSFr) on human cells is described. The number of
      GM-CSFr binding sites on human neutrophils was assessed by using different bead
      standards. Results were compared with those from conventional receptor
      quantification, which was performed by using the radioligand binding assay. A
      high degree of correlation was found between the two methods, although
      quantitative evaluation of GM-CSFr expression on neutrophils performed by flow
      cytometry revealed a somewhat higher number of receptor molecules per cell than
      with that determined by Scatchard analysis. By the flow quantitative approach, we
      measured the GM-CSFr on mobilized CD34-positive cells and obtained results
      similar to those of previously published data. Our data suggest that flow
      cytometric analysis is a simple and reproducible method to detect and quantify
      the presence of GM-CSFr per cell, thus allowing the study of receptor expression
      on different populations selected by gating on the basis of the scatter
      parameters and surface markers. This assay offers the possibility to quantify the
      presence of GM-CSFr on different subsets of normal and pathological cells even if
      samples are too small (such as CD34-positive progenitor cells) for measurement
      with the radioligand binding assay.

PMID- 8866223
TI  - Cell-associated IL-8 in human blood monocytes: analysis by flow cytometry.
AB  - Several cell-associated cytokines, such as interleukin-1 (IL-1) and tumor
      necrosis factor, exist on the cell surface and are biologically active. Although
      extracellular IL-8, a potent chemotactic factor for primarily neutrophils, has
      been studied extensively, cell-associated IL-8 has barely been studied. In this
      study, we analyzed the intracellular and cell-surface IL-8 in human blood
      monocytes in vitro by using flow cytometry and predicted the biological activity
      of the cell-associated IL-8 in vivo. After fixation with paraformaldehyde,
      mononuclear cells were divided into two subgroups. One subgroup was left
      untreated to study cell-associated antigens, and the other subgroup was
      permeabilized with saponin to detect intracellular antigens. In
      lipopolysaccharide (LPS)-stimulated monocytes, IL-8 was detected solely
      intracellularly, whereas both the intracellular and cell-surface IL-1 beta was
      detectable. In a time-course study, the intracellular IL-8 increased in response
      to LPS stimulation, but the cell-surface IL-8 was undetectable throughout the
      course. In an LPS-stimulated monocytic cell line, both ELISA and flow cytometry
      detected the quantitative change of the intracellular IL-8. The dissimilar
      localization between IL-8 and IL-1 beta within cells was confirmed by the
      immunohistochemical analysis. In summary, LPS stimulation induced a time
      dependent increase in intracellular but not cell-surface IL-8 in monocytes. Thus,
      it is unlikely that the cell-associated IL-8 is functioning physiologically. The
      semiquantitative flow cytometric procedure may be useful for simultaneous
      examination for cell-surface and intracellular cytokines.

PMID- 8866224
TI  - Allo-7: a new fluorescent tandem dye for use in flow cytometry.
AB  - This report describes the development of a novel tandem dye by combining
      allophycocyanine (APC) and cyanine dye indotricarbocyanine (CY7) to create ALLO-7
      for use in flow cytometry. The APC donor fluorophore was excited at 647 nm and,
      through resonance energy transfer to the CY7 acceptor, produced fluorescence at >
      780 nm. To test the applicability of this tandem in single and multicolor
      immunofluorescence, a streptavidin conjugate of the tandem (SA-ALLO-7) was used
      for the detection of cell surface antigens on human peripheral blood leukocytes
      (PBL) by indirect immunofluorescence. Human PBL were stained with CD4/ GaM-APC,
      CD3-fluorescein isothiocyanate (FITC), CD14-phycoerythrin (PE), CD19-energy
      coupled dye (phycoerythrin-Texas Red) (ECD), and CD8-biotin with SA-ALLO-7 and
      analyzed for fluorescence on a FACS Vantage using dual-laser excitation (488 and
      647 nm). The results indicated that the percentage of cells positive for each of
      the surface antigens was comparable for single-color controls and multicolor
      samples. The ALLO-7 fluorescence, which was collected with a 730-shortpass
      dichroic mirror and a 790/50-bandpass filter, was clearly resolved from the APC
      fluorescence and that from FITC, PE, and ECD. The SA-ALLO-7 exhibited minimal
      nonspecific binding to PBL monocytes. However, the specific binding of the tandem
      to high-density antigens was clearly identified by positive fluorescence. This
      unique tandem reagent, ALLO-7, provided the capability for dual-color
      immunofluorescence with a 647-nm laser line (or a helium neon laser at 633 nm)
      and provides the potential to perform three-color analysis with a dye-head laser
      (Texas Red, APC, ALLO-7).

PMID- 8866226
TI  - FDA regulation of analyte-specific reagents (ASRs). Implications for nucleic acid
      based molecular testing.

PMID- 8866227
TI  - Detection of the NPM-ALK genomic rearrangement of Ki-1 lymphoma and isolation of
      the involved NPM and ALK introns.
AB  - The breakpoints of the translocation t(2;5)(p23;q35) associated with Ki-1
      positive anaplastic large-cell lymphoma (Ki-1 ALCL) involve a novel tyrosine
      kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) using NPM and ALK primers
      detects a consistent fusion product in Ki-1 ALCL cases with the translocation,
      resulting from genomic breakpoints within the same respective introns of NPM and
      ALK. To examine the feasibility of long-range DNA PCR with the same exonic NPM
      and ALK primers for the detection of the genomic NPM-ALK rearrangement, we
      examined 20 cases of Ki-1 ALCL previously characterized by NPM-ALK RT-PCR. Ten
      cases were positive for the NPM-ALK fusion RNA and 10 were negative. We first
      confirmed that both the NPM and ALK normal introns are relatively short,
      approximately 1 and 2 kb, respectively, suggesting that the largest possible size
      for the chimeric NPM-ALK intron would be about 3 kb. All 10 cases positive by RT
      PCR were also positive by long-range DNA PCR. The DNA PCR products ranged, as
      expected, from the sizes of the normal introns, between 0.5 and 2.5 kb. All 10 RT
      PCR-negative cases were also negative by long-range DNA PCR, and control
      templates for RT-PCR and long-range DNA PCR were successfully amplified. Thus, we
      have shown that the introns involved by the NPM-ALK rearrangement seen in some Ki
      1 lymphomas are relatively short, making the genomic rearrangement amenable to
      reliable detection by long-range DNA PCR. Furthermore, the variability observed
      in the sizes of chimeric introns in evidence against clustering of the genomic
      breakpoints within these introns.

PMID- 8866228
TI  - High-resolution analysis of immunoglobulin heavy-chain gene rearrangements using
      denaturing gradient gel electrophoresis.
AB  - The detection of clonality in B-cell lymphomas has been facilitated by polymerase
      chain reaction (PCR) analysis of the immunoglobulin heavy-chain gene (IgH)
      complementarity determining region 3 (CDR3) and size fractionation by
      polyacrylamide gel electrophoresis (PAGE). However, the detection of minor clonal
      populations and biallelic rearrangements and the isolation of monoclonal products
      from gels are sometimes problematic. This study evaluated whether denaturing
      gradient gel electrophoresis (DGGE), a technique that separates DNA based on
      nucleotide sequence rather than length, could alleviate these problems. A total
      of 32 selected cases was studied with a diagnosis of monoclonal (n = 10),
      polyclonal (n = 9), and indeterminate (n = 13) IgH gene rearrangements, which
      were determined by analysis of seminested IgH CDR3 PCR products in 8% PAGE. These
      cases were evaluated using DGGE of seminested IgH CDR3 PCR products that included
      a 40-bp GC clamp on the Jh primer. DGGE allowed the discrimination of monoclonal
      populations in 9 of 13 cases where 8% PAGE results were indeterminate. In
      addition, DGGE demonstrated biallelic IgH rearrangements in three cases where 8%
      PAGE revealed only one predominant product. DGGE facilitated the purification and
      isolation of clonal IgH CDR3 products for sequencing without prior cloning. As an
      adaptation of current IgH PCR protocols, DGGE can enhance the construction of
      tumor-specific CDR3 primers/probes for investigations of minimal residual
      disease.

PMID- 8866229
TI  - Presence of human herpesvirus type 6 in sporadic lymphoproliferative disorders. A
      comparative study.
AB  - A supportive or causal role for human herpesvirus 6 (HHV-6) in
      lymphoproliferative disorders is still controversial. Different results were
      obtained in both tissue-based and serological investigations. We investigated 243
      lymph node and salivary gland tissue biopsies for the presence of viral DNA by
      using a newly developed, highly sensitive nested polymerase chain reaction
      method. HHV-6 was detected in 39% of the non-Hodgkin's lymphomas, in 52% of
      Hodgkin's diseases, 64% of non-neoplastic lymph nodes, 23% of tumor metastases,
      and 50% of salivary gland biopsies. When correlating the patients' ages with the
      occurrence of HHV-6, we found a significantly higher percentage of positive
      samples in patients younger than 60 years of age (54%) than in older patients
      (35%). This age-related difference was found in all the lymphoproliferative
      disorders studied as well as in salivary gland biopsies. Taking patient's ages
      into account, we found no significant difference between the various groups of
      disorders concerning the percentage of HHV-6-positive samples.

PMID- 8866230
TI  - High-sensitivity detection of minimal residual breast carcinoma using the
      polymerase chain reaction and primers for cytokeratin 19.
AB  - We have developed a reverse transcriptase-polymerase chain reaction (RT-PCR)
      assay to identify breast carcinoma cells in bone marrow aspirates with high
      sensitivity and specificity. This assay relies on the detection of cytokeratin 19
      (K19) RNA by nested primer PCR followed by annealing to a (32P)-labeled internal
      sequence probe and autoradiography. In reconstitution experiments, this assay is
      capable of detecting 10 fg of admixed mammary tumor RNA in 1 microgram of normal
      marrow RNA (a dilution of 1:10(7)). Thirty of 30 primary breast tumor specimens,
      19 of 19 cytologically positive bone marrow aspirate specimens, and three of 11
      aspirate negative/biopsy positive specimens showed detectable K19 transcript.
      This assay shows high specificity, with 50 of 52 negative control aspirates
      showing no detectable amplification product. False-positive amplification was
      noted in two of 18 aspirates obtained from patients with active chronic
      myelogenous leukemia. Of stage II and III postsurgical breast carcinoma patients
      with histologically negative bone marrows and no radiographic bone disease, 14 of
      30 were K19 positive by PCR. RT-PCR analysis of K19 transcript is a highly
      sensitive and specific method of detecting and monitoring low-level metastatic
      disease in patients with primary carcinoma of the breast. The presence of K19 RNA
      in histologically negative bone marrows suggests that this assay may prove a
      powerful monitor for patients undergoing curative therapy as well as a novel
      prognostic indicator.

PMID- 8866231
TI  - Variations in c-erbB-2 proto-oncogene status in breast cancer tumors as detected
      by two different cDNA probes.
AB  - We examined 232 breast carcinomas for c-erbB-2 amplification by Southern analysis
      using two different cDNA probes. Using these same probes, 95 of these tumors were
      also examined for mRNA expression by Northern analysis. Amplification was
      detected in 20 and 17% of the tumors with the probes pHER 2 and pCER 204,
      respectively, but only 10% showed amplification with both probes. A significantly
      higher incidence (p < 0.01) of mRNA overexpression was detected with the pHER 2
      probe (34%) compared with the pCER 204 probe (16%), with only 11% of tumors
      demonstrating overexpression with both probes. A total of 10 tumors (11%)
      exhibited amplification as well as overexpression with pHER 2, whereas
      significantly fewer (3%) manifested both abnormalities with the larger pCER 204
      probe (p < 0.05). Amplification of c-erbB-2, as detected with the pHER 2 probe
      but not with the pCER 204 probe, was significantly associated with the absence of
      both estrogen and progesterone receptors (p < 0.05 and p < 0.01, respectively).
      No relationship was found with other clinical prognostic indicators, such as
      nodal involvement and metastases. As determined by either probe, overexpression
      was not associated with prognostic indicators. There was no significant
      difference in the c-erbB-2 status of tumors from different racial groups.

PMID- 8866232
TI  - Correlation between p53 immunostaining patterns and gene sequence mutations in
      breast carcinoma.
AB  - We performed p53 immunostaining in 82 invasive breast carcinomas by using two
      commercially available antibodies, one of which (DO7) was employed in formalin
      fixed paraffin-embedded sections. The other antibody (PAb1801) was evaluated in
      corresponding acetone-fixed cryostat sections. A greater percent of cases were
      immunostained with DO7 compared to PAb1801 (52% vs 33%); however, the staining
      was more often heterogeneous (6-50% cells positive) or focal (< or = 5% cells
      positive) with DO7 (9% vs 31%). To investigate the genetic relevance of p53
      immunostaining, single-strand conformational polymorphism (SSCP) analysis and DNA
      sequencing were performed on exons 2-11 by using archival tissue samples of 18
      cases that were selected on the basis of certain immunostaining patterns. Two
      (33%) of six tumors with negative staining for DO7 had gene sequence mutations;
      however, one of these mutations was a base-pair deletion that caused a reading
      frame shift and the other was a base-pair insertion that resulted in a stop
      codon. Both of these tumors exhibited immunostaining with PAb1801, although it
      was weak and cytoplasmic in one case. Conversely, three (30%) of 10 tumors
      showing immunoreactivity in 6-100% of cells with both reagents lacked a gene
      sequence mutation. Of the remaining seven tumors that were positive by SSCP, six
      contained a point mutation resulting in a base-pair substitution. Despite repeat
      analyses, one of the cases positive by SSCP failed to demonstrate a mutation in
      the sequenced exons. Four (80%) of five cases with heterogeneous DO7
      immunoreactivity (that is, 6-50% of nuclei positive) were positive for gene
      sequence mutation. Neither of two cases showing focal DO7 nuclear staining in <
      5% of tumor cells contained a mutation in the sequenced exons, and neither of
      these cases was strongly positive with PAb1801. Staining for either antibody was
      significantly associated with adverse outcome, as determined by disease
      recurrence at 52 months median follow-up (DO7, p = 0.01; and PAb1801 p = 0.002,
      chi-squared test). We conclude that a variety of factors may account for
      discrepancies when immunohistology is used to evaluate p53 status. These include
      fixation artifacts, differing epitope specificities of monoclonal reagents,
      presence of immunohistologically "silent" mutations and, possibly, aberrant
      overexpression of wild-type protein.

PMID- 8866233
TI  - Molecular genetic and immunohistochemical analysis of the tumor suppressor genes
      Rb and p53 in palmar and aggressive fibromatosis.
AB  - This pilot project analyzed the tumor suppressor genes p53 and Rb in 13 cases of
      aggressive fibromatoses and six cases of palmar fibromatoses (Dupuytren
      contracture). Immunohistochemistry, reverse transcription polymerase chain
      reaction, polymerase chain reaction followed by single-strand confirmation
      polymorphism analysis, and Southern blot to detect gene rearrangements were used.
      No abnormalities were detected in p53. The aggressive fibromatoses demonstrated a
      lack of Rb immunohistochemical staining and decreased mRNA for Rb. No structural
      mutation in the coding sequence of the Rb gene was detected. The decreased level
      of Rb gene expression, despite a normal coding sequence, may indicate increased
      proliferation and may suggest potential treatment schemes.

PMID- 8866234
TI  - Tumor suppressor p53 gene mutation in squamous cell carcinoma of the larynx.
AB  - Using polymerase chain reaction (PCR)-SSCP (single-strand conformation
      polymorphism) and PCR-DNA sequencing analysis, we screened 61 cases of laryngeal
      squamous cell carcinoma for mutations in exons 5-8 of the p53 gene. Mutations
      were found in 31.3% (19 of 61) of the laryngeal cancers. Seventeen of 19 (84.2%)
      cases showing p53 gene mutations were stage III and IV, which suggests that p53
      gene mutation is a rather late event in tumor development and is involved in the
      progression of laryngeal squamous cell carcinoma. A high frequency of G:C to T:A
      transversion (50%, seven of 14), especially G to T (35.7%, five of 14), was noted
      in laryngeal carcinoma samples in our study. This finding may point toward an
      environmental carcinogen (such as tobacco smoke) as an important agent in the
      genesis of laryngeal squamous cell carcinoma. Most of the p53 gene mutations (18
      of 19) found in our studies could change the protein and thus may cause an
      inactivation of the p53 tumor suppressor gene, strongly suggesting that p53 gene
      mutation plays a crucial role in the progression of laryngeal carcinoma.

PMID- 8866235
TI  - Nonradioisotopic detection and typing of human papillomaviruses by use of
      polymerase chain reaction and single-strand conformation polymorphism.
AB  - The polymerase chain reaction (PCR), used to detect human papillomavirus (HPV),
      is finding increasing applications in clinical laboratories. The standard method
      of analysis to detect amplified PCR products is ethidium bromide gel
      electrophoresis combined with labor intensive blot hybridization. In this study,
      we describe single-strand conformation polymorphism (SSCP) to detect and genotype
      simultaneously general primer GP5+/GP6+ amplified HPV DNA using semiautomated
      electrophoresis on polyacrylamide gels (PAGE) combined with sensitive silver
      staining. To establish a standard for the band patterns of the various HPV types,
      we used HPV plasmid DNA, which allowed us to distinguish HPV 6, 11, 16, 18, 31,
      33, 35, 45, 51, 52, 56, and 58, covering the most frequently recognized types.
      All the types tested are separated from each other, demonstrating diverse band
      patterns, HPV 16 being the most distinct. We also investigated PCR-SSCP for HPV
      detection and typing of 86 cervical biopsies diagnosed as cervical
      intraepithelial neoplasia (CIN) I-III and known to be HPV positive by PCR-slot
      blot hybridization and in situ hybridization. The correlation with SSCP was 91%
      for in situ hybridization and 98% for PCR-slot blot hybridization. SSCP is
      reproducible and specific. Its sensitivity is comparable to slot-blot
      hybridization. The interval to SSCP is approximately 2 h after PCR compared with
      several days' work when using conventional blot hybridization. We concluded that
      SSCP may be more advantageous than other PCR-based typing technologies.

PMID- 8866236
TI  - Loss of heterozygosity and microsatellite instability at the retinoblastoma locus
      in osteosarcomas.
AB  - Studies of osteosarcoma cell lines or frozen tissue have detected loss of
      heterozygosity (LOH) at the retinoblastoma (RB) locus by Southern blot analysis
      or restriction fragment length polymorphism. Most archived clinical specimens
      cannot be analyzed by these techniques. We analyzed formalin-fixed, paraffin
      embedded samples from 19 cases of osteosarcoma for molecular changes at the RB
      locus using polymerase chain reaction amplification of polymorphic short tandem
      repeat sequences (microsatellite repeats). Four repeat sequences, two within and
      two flanking the RB gene, were analyzed. Fourteen of 18 informative cases (78%)
      showed molecular changes at the RB locus. LOH was identified in 13 cases (72%).
      Unexpectedly, microsatellite instability (MI) was found in eight cases (44%). All
      of the cases of MI involved alterations of more than one repeat unit, and six of
      eight were associated with LOH. LOH was identified at three unlinked loci in one
      case and at a single locus in another Microsatellite analysis of archival tissue
      yields prevalence rates of LOH comparable to those found by other methods and has
      the added advantage of showing MI. The ability to use formalin-fixed, paraffin
      embedded tissue extends genetic analysis to routinely processed surgical material
      and may permit molecular confirmation of challenging cases of osteosarcoma.

PMID- 8866237
TI  - Comparison of methods for extracting DNA from formalin-fixed paraffin sections
      for nonisotopic PCR.
AB  - DNA was extracted from unstained 5-microns sections of neutral buffered 10%
      formalin-fixed paraffin-embedded tissue by proteinase K digestion without
      detergents followed by boiling, proteinase K digestion with ionic detergents with
      and without phenol chloroform extraction and ethanol precipitation, sonication
      with proteinase K followed by boiling, or boiling alone. Serial 1:10 dilutions of
      the extracted DNA were subject to polymerase chain reaction (PCR) amplification
      of a 255-bp portion of the p53 gene. Digestion with proteinase K without ionic
      detergents followed by boiling (without phenol chloroform extraction) gave the
      best yield, enabling visualization of ethidium bromide-stained PCR product from a
      DNA dilution corresponding to 0.1 mm2 of tissue containing of the order of 10(3)
      nuclear profiles. Proteinase K digestion with detergents followed by phenol
      chloroform extraction was no more effective than simple boiling. Although the
      success of PCR from preserved tissue will vary with the fixative and size of the
      amplified fragment, DNA extracted with this optimized method can be used for
      identification of viruses, loss of heterozygosity, and immunoglobulin gene
      rearrangements in paraffin-embedded tissue without radioisotopes.

PMID- 8866238
TI  - Spatial relationships of utrophin, dystrophin, beta-dystroglycan and beta
      spectrin to acetylcholine receptor clusters during postnatal maturation of the
      rat neuromuscular junction.
AB  - At the adult mammalian neuromuscular junction, acetylcholine receptors are
      concentrated at the tops of the postsynaptic folds and voltage-gated sodium
      channels are concentrated in their depths. It is likely that this arrangement
      involves linkage of the ion channels to components of the underlying membrane
      cytoskeleton. In rats, the mature distribution of acetylcholine receptors arises
      as part of the developmental remodelling of the junctional region during the
      first few weeks after birth. We have followed the changes during this period in
      the distribution of four proteins associated with the postsynaptic cytoskeleton
      at mature neuromuscular junctions (utrophin, dystrophin, beta-dystroglycan and
      beta-spectrin) to see if any of them co-localizes with acetylcholine receptors
      during the remodelling process, as would be required if it serves to link
      acetylcholine receptors to the cytoskeleton. Each protein was visualized with
      specific monoclonal antibodies and its distribution at various stages was
      compared with that of the acetylcholine receptors, labelled with alpha
      bungarotoxin. We also related the changes in distribution of these postsynaptic
      proteins to the main stages in fold formation and, in the Discussion, to reported
      observations of the accumulation of voltage gated sodium channels during
      development. Our results show that utrophin labelling is closely co-localized
      with that of acetylcholine receptors throughout postnatal maturation. beta
      dystroglycan labelling is present at most sites of high acetylcholine receptors
      density throughout maturation although it often extends beyond the region of
      highest acetylcholine receptors labelling density. By contrast, dystrophin and
      beta-spectrin labelling is not consistently concentrated at most neuromuscular
      junctions until after P7 and P14 respectively.

PMID- 8866239
TI  - The cone synapses of DB1 diffuse, DB6 diffuse and invaginating midget, bipolar
      cells of a primate retina.
AB  - The distribution of synapses between cones and two types of diffuse cone bipolar
      cell in a rhesus monkey retina is described. The dendrites of representative
      Golgi-stained cells of each of the diffuse cone bipolar cell types DB1 and DB6
      were serially sectioned for EM examination. Bipolar cells of the DB1 type have
      axons terminating in the outer half of the inner plexiform layer. The dendrites
      of the cell examined were postsynaptic to seven cones at 71 basal synapses; in
      addition, they had two ribbon synapses with one cone, and one with another. A DB6
      type of bipolar cell has axons ending in the inner half of the inner plexiform
      layer. The dendrites of the cell examined received input from seven cones at 30
      ribbon synapses; in addition there were 13 basal junctions distributed between
      five of the seven cones contacted. Two invaginating midget bipolar cells were
      found to be postsynaptic at 25 and 26 ribbon synapses of cone pedicles containing
      44 and 40 ribbons respectively. These results combined with our previously
      published work, show that the position and number of synapses is characteristic
      for each category of cell. Those bipolar cells (flat) making basal synapses have
      more sites of synaptic contact with the cones than those bipolar cells
      (invaginating) with predominantly ribbon synaptic input. Over 95% of the cone
      junctions of the three types of diffuse bipolar cell, DB1, DB2 and DB3, are
      basal; and their axons always end in the a- (Off-) layer of the inner plexiform
      layer. All three types of diffuse invaginating cone bipolar cell, DB4, DB5 & DB6,
      have axons terminating in the b- (On-) layer of the inner plexiform layer; their
      dendrites are predominantly postsynaptic as central elements invaginating at the
      cone triads. However, unlike invaginating midget bipolar cells, whose dendrites
      are exclusively postsynaptic at ribbon synapses, between 10% (DB5) and 40% (DB4
      and DB6) of the cone input to diffuse invaginating bipolar cells is through basal
      junctions. These data are discussed in the context of recent work on the synapses
      between foveal cones and their bipolar cells.

PMID- 8866240
TI  - Glutamate immunoreactivity in the tiger salamander retina differentiates between
      GABA-immunoreactive and glycine-immunoreactive amacrine cells.
AB  - A higher proportion of retinal amacrine cells, largely thought to be inhibitory,
      in tiger salamander retina are immunoreactive (+) for the excitatory amino acid
      glutamate than for either of the inhibitory amino acids, GABA and glycine. The
      colocalizations of glutamate immunoreactivity, GABA immunoreactivity and glycine
      immunoreactivity were studied in the proximal retina of tiger salamander using
      postembedding immunocytochemical methods in consecutive semithin sections. A
      considerable degree of colocalization was observed between glutamate
      immunoreactivity and GABA immunoreactivity and to a lesser extent with glycine
      immunoreactivity. No glutamate-immunoreactive cells were single labelled in INL3
      (proximal inner nuclear), 12% were single labelled in INL2 (mid INL; these are
      bipolar cells), 62% were singled labelled in the ganglion cell layer (GCL) and
      likely to be ganglion cells. Single-labelled glycine-immunoreactive cells
      comprised 16% in INL3, 2%; INL2 and GCL, 0%). Glutamate immunoreactivity co
      localized four times as often with GABA immunoreactivity than glycine
      immunoreactivity in INL3 (77% versus 19%), comparably in INL2 (37% and 32%) and
      six times as often in the GCL (29% versus 5%). A computerized image analysis of
      the relative intensities of glutamate immunoreactivity in GABA
      immunoreactive/glutamate-immunoreactive and glycine-immunoreactive/glutamate
      immunoreactive double labelled amacrine cells in INL3 revealed that all glycine
      immunoreactive cells contained low intensities of glutamate immunoreactivity;
      whereas 35% of GABA-positive cells had medium to high intensities of glutamate
      immunoreactivity. There was a significant correlation (r = 0.44; p < 0.01)
      between the intensities of glutamate immunoreactivity and GABA immunoreactivity
      in GABA-immunoreactive/glutamate-immunoreactive amacrine cells. The common
      colocalization of glutamate immunoreactivity with GABA immunoreactivity and the
      positive correlation of their relative intensities suggests that glutamate is
      likely to serve as a precursor for GABA synthesis. However, intense glutamate
      immunoreactivity in 5% of the amacrine cells suggests a transmitter function.
      Glycine-immunoreactive amacrine cells contained little or no glutamate
      immunoreactivity, suggesting a minimal role for glutamate as a neurotransmitter
      in these cells. The major distribution of intense glutamate immunoreactivity is
      in bipolar cells and ganglion cells, consistent with data suggesting that
      glutamate is the transmitter in the retinal through pathway.

PMID- 8866241
TI  - Immunocytochemical localization of chromogranin A in the normal and stimulated
      hypothalamo-neurohypophysial system of the rat.
AB  - Chromogranin A (CGA) is a calcium-binding glycoprotein thought to be the
      precursor of several peptides with defined biological activity. Chromogranin A
      has been localized in most endocrine cells and many neurons in the CNS. Here we
      studied its expression in neurons of the hypothalamo-neurohypophysial system,
      which secrete the neurohormones oxytocin and vasopressin. Light and electron
      microscopic immunocytochemistry and immunoblot analysis with antibodies specific
      for CGA revealed high levels of chromogranin A immunoreactivity throughout the
      hypothalamo-neurohypophysial system. In the supraoptic and paraventricular
      nuclei, it was characterized by intracytoplasmic labelling of magnocellular
      somata and processes and of certain astrocytes. Extensive labelling of fibres and
      dilatations characterized the internal layer of the median eminence and the
      neurohypophysis, transit and terminal site of the neurosecretory axons,
      respectively. Tanycyte-like cells in the median eminence also displayed reaction.
      Simultaneous immunofluorescence showed that oxytocinergic and vaso-pressinergic
      neurons contain chromogranin A. Electron microscopy revealed that chromogranin A
      immunoreactivity (visualized by pre-embedding immunoperoxidase or silver-enhanced
      colloidal gold techniques) was associated with neuro-secretory granules in
      hypothalamo-neurohypophysial system neurons. In astrocytes and pituicytes, it was
      seen over the cytoplasm and glial filaments. In tissue from colchicine-treated or
      immobilization-stressed rats, it was clear that chromogranin A immunoreactivity
      in the hypothalamus was confined to the hypothalamo-neurohypophysial system. In
      rats in which neurohypophysial secretion was strongly stimulated by dehydration,
      immunocytochemistry showed that hypothalamo-neurohypophysial system
      immunoreactivity significantly increased in the magnocellular nuclei but
      decreased in the neurohypophysis. On the other hand, chromogranin A distribution
      was not markedly affected by stress or lactation. These observations demonstrate
      that chromogranin A is present in neurons and, to a lesser degree, glial cells of
      the hypothalamo-neurohypophysial system and that its expression is closely
      related to that of the neurohypophysial peptides.

PMID- 8866243
TI  - Brain and pituitary melatonin receptors in male rat during post-natal and
      pubertal development and the effect of pinealectomy and testosterone
      manipulation.
AB  - Using quantitative autoradiography, melatonin receptors have been studied during
      post-natal and pubertal development of the rat in 2 brain and 2 pituitary
      structures. In the pars distalis of anterior pituitary, melatonin receptors
      decrease gradually in density after birth and disappear in 30 day-old animals. In
      contrast melatonin binding is only expressed in the paraventricular nuclei of the
      thalamus at the age of 21-23 days and is always present in adult animals. In the
      suprachiasmatic nuclei and in the pars tuberalis of the pituitary, melatonin
      receptor density decreases after birth, remains stable for approximately 1 month
      and increases again at puberty to reach the birth values in the adult. This
      increase was absent in pinealectomized and in castrated animals but present in
      castrated animals receiving testosterone suggesting that it depends upon
      circulating testosterone and melatonin levels. These results show that melatonin
      receptors are differentially regulated during post-natal development in each of
      the 4 structures studied, and that melatonin and testosterone are 2 factors which
      could be involved in the regulation of melatonin receptor density in the
      suprachiasmatic nuclei and pars tuberalis.

PMID- 8866242
TI  - Cytoskeleton-membrane interactions at the postsynaptic density of Xenopus
      neuromuscular junctions.
AB  - Acetylcholine receptors of mature muscle fibres are concentrated in the
      postsynaptic membrane by mechanisms that are not yet understood. As one
      possibility, receptors might be anchored to cytoskeletal elements in the
      postsynaptic density that is located beneath the membrane where receptors are
      concentrated. To address this possibility, we examined the cytoskeleton at the
      postsynaptic density and determined the organization of cytoskeletal filaments
      relative to clustered acetylcholine receptors (AChR). Xenopus nerve-muscle co
      cultures were sheared to expose the cytoplasmic membrane surface, then quick
      frozen, deep-etched, and rotary-replicated. Areas with a high concentration of
      AChR had aggregates of particles protruding from the cytoplasmic surface of the
      membrane, with actin microfilaments attached to and cross-linking the aggregates.
      Microfilaments contacted only a few of the particles in an aggregate. These
      findings suggest that short-range interactions may bind individual AChR into
      small aggregates, while microfilaments tie these aggregates together at the nerve
      muscle junction.

PMID- 8866244
TI  - The kappa-opioid receptor agonist MR-2034 stimulates the rat hypothalamic
      pituitary-adrenal axis: studies in vivo and in vitro.
AB  - There is increasing evidence that opiates not only have analgesic properties, but
      also regulate mechanisms activated during the stress response, such as the
      hypothalamic-pituitary-adrenal (HPA) axis. Indeed, opioid-containing neurons
      innervate the paraventricular nucleus and the median eminence, thus modulating
      inputs to ACTH-controlling neurons. In addition, dynorphin (the endogenous ligand
      of the kappa-opioid receptor)-like peptides have been found co-localized with
      corticotrophin-releasing hormone (CRH) and are believed to be co-secreted with it
      in the hypophyseal portal circulation to modulate ACTH release. In this study, we
      evaluated the effects of the selective kappa-opioid receptor agonist MR-2034 [(-)
      N-(2-tetrahydrofurfuryl)-normetazocine] on the HPA axis in vivo and in vitro. MR
      2034 was given intravenously to catheterized, freely moving, male Sprague-Dawley
      rats and serial blood samples were collected for ACTH and corticosterone (B)
      measurements. We evaluated also the site of MR-2034 action on the HPA axis in
      vivo, after the administration of alpha-helical CRH9-41, a CRH receptor
      antagonist, on hypothalamic CRH, pituitary ACTH, and B release in vitro. MR-2034
      increased plasma ACTH and B levels in a dose-related fashion and this effect was
      antagonized by the selective kappa-opioid receptor antagonist MR-1452. In the
      presence of alpha-helical CRH9-41, the responses of plasma ACTH and B to MR-2034
      were blunted significantly, suggesting that this compound activates the HPA axis
      through a CRH-dependent mechanism. Accordingly, MR-2034 stimulated hypothalamic
      CRH release in vitro in a concentration-dependent fashion and this effect was
      antagonized dose-dependently by MR-1452. However, the stimulatory effect of MR
      2034 on plasma ACTH and B in vivo was not completely abolished by alpha-helical
      CRH9-41, suggesting that an additional, CRH-independent, mechanism was involved.
      Indeed, MR-2034 was able to stimulate basal ACTH output in a dose-dependent
      manner and this effect was antagonized by MR-1452 in vitro. On the other hand, MR
      2034 did not have any effect on B release from adrenocortical cells or adrenal
      quarters in vitro. These results show that the benzomorphan MR-2034 stimulates
      the HPA axis in the rat by acting at the hypothalamic and the pituitary level. We
      hypothesize that endogenous kappa-opioid peptides not only act at the pituitary
      level to increase ACTH output, but may also act at the hypothalamic level to
      increase CRH release through an autocrine and/or ultrashort positive feedback
      mechanism.

PMID- 8866245
TI  - Neurotensin receptor down-regulation induced by dexamethasone and forskolin in
      rat hypothalamic cultures is mediated by endogenous neurotensin.
AB  - Neurotensin (NT) has been shown to be involved in neuroendocrine regulation, and
      the presence of both the peptide and its receptors has been demonstrated in the
      hypothalamus. In the present study, we show that hypothalamic neurons in primary
      cultures express the neurotensin receptor (NTR) and we examined a possible
      regulation of this receptor by glucocorticoids and activators of adenylate
      cyclase. In the hypothalamic cultures, 125I-NT bound to a single class of binding
      sites, presenting a selectivity similar to that observed for the high-affinity
      NTR previously described in the adult rat brain. Radioautographic studies
      demonstrated that these 125I-NT binding sites were present on 3% of the neurons.
      A 48-h treatment with forskolin (fsk) decreased 125I-NT binding by 30%. No effect
      of dexamethasone (dex) alone was found on that parameter. However, a combined
      treatment with both agents led to a 40% decrease in 125I-NT binding,
      corresponding to a reduced number of binding sites, and to a 68% decrease in the
      amount of NTR mRNA. In parallel, the dex plus forsk treatment increased NT
      release in the incubation medium. Moreover, the decreases in 125I-NT binding and
      NTR mRNA induced by this treatment were abolished in the presence of an anti-NT
      antibody or SR 48692, a non-peptidic antagonist of NTR, suggesting that the down
      regulation of NTR observed after dex plus fsk treatment was mediated by the
      release of endogenous NT. Agonist-induced down-regulation of the NTR in this
      system was confirmed by the application of an exogenous NT analogue, JMV 449. The
      present findings indicate that, in hypothalamic cultures, dex and fsk indirectly
      down-regulate NTR expression via the release of endogenous NT.

PMID- 8866246
TI  - 11 beta-Hydroxysteroid dehydrogenase activity in the hippocampus: implications
      for in vivo corticosterone receptor binding and cell nuclear retention.
AB  - In this study a possible role of 11 beta-hydroxysteroid dehydrogenase (11 beta
      HSD) in altering the access of corticosteroids to their receptors in the
      hippocampus is investigated. In vitro, oxidation of corticosterone to 11
      dehydrocorticosterone (11-DHC) was demonstrated in hippocampal homogenates.
      Glycyrrhetinic acid (GE) and carbenoxolone (CBX) were potent inhibitors of 11
      beta-HSD activity and did not display affinity for mineralocorticoid (MRs) nor
      glucocorticoid receptors (GRs). Intracerebroventricular injection of CBX in vivo
      (ED50 approximately 30 micrograms) decreased oxidative activity in hippocampal
      homogenates, as demonstrated in vitro. In vitro, in hippocampal slices, cell
      nuclear retention of tritiated corticosterone, but not aldosterone, was markedly
      enhanced in the presence of GE, which at a concentration of 20 nM was found to
      inhibit 11 beta-HSD activity by about 50% in the intact cell preparation. In
      contrast to the effect on in vitro cell nuclear uptake, in vivo autoradiography
      revealed that retention of corticosterone in the hippocampal cell nuclei was not
      affected after intracerebroventricular treatment with CBX. We conclude that
      hippocampal 11 beta-HSD activity does not alter binding of low amounts of
      corticosterone to MRs in vivo, but we cannot exclude that the enzyme may modulate
      access to corticosteroid receptors under certain circumstances.

PMID- 8866247
TI  - Effects of ovariectomy on GnRH neuronal morphology in rhesus monkey (Macaca
      mulatta).
AB  - Gonadotropin releasing hormone (GnRH) neurons are typically simple, fusiform
      cells; however, over the course of prepubertal development increasing numbers
      take on a 'spiny' appearance. Following gonadectomy there is a decrease in the
      frequency of these spiny GnRH neurons. These observations which were made in the
      rat suggest that GnRH neurons are directly affected by the gonadal steroid
      milieu, though they do not themselves contain receptors for these steroidal
      hormones. In that there are important species differences in the hypothalamic
      pituitary-gonadal axis between rats and primates, the present study was
      undertaken to determine whether a reduction in ovarian hormones would produce
      similar changes in the morphology of GnRH neurons in the monkey. A further aim
      was to determine whether such changes were localized to a specific brain region.
      Immunocytochemically defined GnRH neurons were compared in adult rhesus macaques
      which had been ovariectomized for 6 weeks to 2 years (n = 7) and intact, cycling
      animals (n = 8). Within the intact group, there were significantly more spiny
      GnRH neurons in the medial basal hypothalamus (MBH) than in the preoptic area
      (POA) (about 50% of the total in the MBH compared to 33% in the POA). Following
      ovariectomy the frequency of spiny cells in the MBH dropped to less than 30%, but
      was not significantly reduced in the POA. These results suggest that changes in
      systemic gonadal steroid levels result in changes in the morphology of GnRH
      neurons preferentially in the MBH, a region that is considered critical in the
      generation of GnRH pulsatile release in the monkey.

PMID- 8866248
TI  - Expression of somatostatin receptor (SSTR) subtypes in pituitary adenomas:
      quantitative analysis of SSTR2 mRNA by reverse transcription-polymerase chain
      reaction.
AB  - The expression of somatostatin receptor (SSTR) subtypes and relative abundance of
      SSTR2 mRNA were examined in 18 pituitary adenomas using the reverse transcription
      polymerase chain reaction (RT-PCR) method. SSTR1 and SSTR2 were expressed in all
      pituitary adenomas examined. Six of 9 somatotroph adenomas, 1 of 4 lactotroph
      adenomas and 1 of 2 thyrotroph adenomas also expressed SSTR5. SSTR3 and SSTR4
      mRNAs were detected in 1 and 2 cases of somatotroph adenoma, respectively. SSTR2
      mRNA expression was quantified by comparison with the PCR cycle-dependent
      amplification of beta-actin or cyclophilin. The relative abundance of SSTR2 mRNA
      varied greatly among adenomas with more than a 1000-fold difference. SSTR2 mRNAs
      in lactotroph adenomas were less abundant (P < 0.01) than those in somatotroph
      adenomas. No significant correlation was found between the relative abundance of
      SSTR2 mRNA levels and GH sensitivity to octreotide administration. However, one
      of the thyrotroph adenomas exhibited marked shrinkage in tumor size after
      octreotide therapy, in which SSTR2 mRNA was the most abundant among the adenomas
      examined. GH sensitivity to octreotide was not significantly different between
      SSTR5 mRNA positive and negative adenomas. In conclusion, SSTR2 mRNA levels
      varied greatly among pituitary adenomas but were not correlated with GH
      sensitivity to octreotide. Further investigations of functional SSTR subtype
      proteins and of postreceptor signal transductions are required to clarify the
      molecular mechanisms of octreotide action.

PMID- 8866249
TI  - Changes in pineal indoleamines in rats after single melatonin injections:
      evidence for a diurnal sensitivity to melatonin.
AB  - We recently determined that melatonin stimulated serotonin (5-HT) secretion from
      rat pineal glands by increasing 5-HT release from the pinealocytes (microM
      melatonin concentrations) and by inhibiting 5-HT uptake in the pineal sympathetic
      nerve endings (mM melatonin concentrations). The present study investigated
      whether a single melatonin injection could alter the content of indoleamines in
      the rat pineal gland, as well as its possible dependence on the daytime of
      administration. Melatonin (150 micrograms/kg) was i.p. injected at 8 time points
      (11.00 h, 14.00 h, 17.00 h, 20.00 h, 23.00 h, 02.00 h, 05.00 h and 08.00 h) to
      rats kept in 12:12 h light:dark cycle (lights on at 07.00 h). Melatonin
      injections in the afternoon (17:00 h) and late in the nighttime (02.00 h and
      05.00 h) decreased pineal 5-HT content 90 min later. The levels of 5
      hydroxyindoleacetic acid (5-HIAA) were also decreased 90 min after the melatonin
      treatment at 14.00 h, 17.00 h and 02.00 h. The effect of melatonin on 5-HT
      content was a long-fasting effect (still evident after 180 min) only when
      injected at 02.00 h, whereas 5-HIAA levels were found to be decreased 180 min
      after melatonin treatment at 14.00 h and 23.00 h. No changes in these compounds
      were detected 240 min after melatonin treatment. Moreover, melatonin did not
      change 5-hydroxytryptophan levels at any of the daytime points studied. By
      contrast, 90 min after the injection of melatonin at 20.00 h, an increased
      content of pineal N-acetylserotonin was observed. This effect of melatonin could
      be mediated through a phase alteration of the pineal N-acetyltransferase activity
      rhythm by acting on the suprachiasmatic clock, although a direct melatonin effect
      on the pineal rhythmic function cannot be excluded. The effects of the hormone on
      5-HT and 5-HIAA contents agree with previous findings on the inhibitory effect of
      pharmacological doses of melatonin on pineal 5-HT uptake, which presumably would
      result in a decreased intraneuronal content of 5-HT and its acid metabolite.
      These data point to an acute regulatory action of exogenous melatonin on the
      pineal melatonin synthesis pathway which seems to be limited to two daytime
      phases; the afternoon-early evening period and the second half of the night.

PMID- 8866250
TI  - Prenatal androgens defeminize activation of GnRH neurons in response to estradiol
      stimulation.
AB  - To determine if prenatal androgens prevent activation of GnRH neurons in response
      to estradiol stimulation, Fos colocalization with GnRH was compared in the brains
      of normal female lambs, normal males, and androgenized females in response to a
      surge-inducing dose of estradiol. Blood samples were collected every 1-2 h for 6
      h before estradiol treatment up to the time of sacrifice at 17-19 h post
      treatment. Following perfusion, 60 micrograms coronal brain sections were
      immunostained for Fos (1:1000, Santa Cruz Biochemicals) and GnRH (1:40,000, LR-1)
      using NiCl-enhanced and unenhanced DAB, respectively. Although LH secretion
      increased in females before sacrifice, no increase was observed in males or
      androgenized females. Despite differences in LH secretion, the number and
      distribution of GnRH neurons was not sexually dimorphic. Moreover, Fos
      immunostaining was visible throughout steroid-responsive limbic regions in all
      three groups of lambs. However, the colocalization of Fos with GnRH was highly
      sexually dimorphic. In females perfused after the peak of the LH surge, 65.7% of
      GnRH neurons in the preoptic area, anterior hypothalamus, and mediobasal
      hypothalamus expressed Fos, whereas only 1.7% of GnRH neurons were Fos-positive
      in males and androgenized females. These findings indicate that sex differences
      in the activation of GnRH neurons in response to estradiol are determined
      prenatally through the actions of testosterone.

PMID- 8866251
TI  - Sexual differentiation of the surge mode of gonadotropin secretion: prenatal
      androgens abolish the gonadotropin-releasing hormone surge in the sheep.
AB  - In sheep, the surge mode of gonadotropin secretion is sexually differentiated,
      i.e. the LH surge is present in the female, but not in the male. The present
      study tested the hypothesis that sexual differentiation of the LH surge mechanism
      reflects a sex difference in the pattern of GnRH, and that prenatal androgens
      abolish the surge mode of GnRH secretion. We monitored the pattern of GnRH
      secretion in pituitary portal blood after acute treatment with estradiol in
      gonadectomized postpubertal males (n = 6), females (n = 6), and androgenized
      females (exposed prenatally to testosterone from day 30-90 in gestation, n = 7).
      Four capsules, each containing a 30-mm column of estradiol were implanted s.c.
      into each lamb to produce high physiologic concentrations of the hormone.
      Beginning 7 h later, portal and peripheral blood samples were collected hourly
      for 48 h for measurement of GnRH and LH, respectively. All females exhibited a
      GnRH surge beginning 13.0 +/- 0.4 h after estradiol treatment; this was
      accompanied by an LH surge. By contrast, only one male produced a small surge in
      GnRH (1.7 pg/min) with a latency of 32 h; a corresponding increase in LH occurred
      in this male. Likewise, among the androgenized females, only one exhibited GnRH
      and LH surges which began at about 22 h after estradiol treatment. Some of the
      androgenized females had sporadic increases in GnRH which were of lower amplitude
      than in the control females, and were unaccompanied by rises in LH. These
      findings provide the first direct evidence that the sex difference in the surge
      mode of LH secretion results from the sexual differentiation of the pattern of
      GnRH release. The study also suggests that androgens during prenatal development
      abolish the GnRH surge and subsequently, the generation of the LH surge.

PMID- 8866252
TI  - Phosphorylation of CREB in ovine pars tuberalis is regulated both by cyclic AMP
      dependent and cyclic AMP-independent mechanisms.
AB  - This study used a combination of Western blotting and immunocytochemistry to test
      whether signalling pathways independent of cyclic AMP have the potential to
      induce phospho-CREB (pCREB)-like immunoreactivity (-ir) in the oPT. Western blot
      analysis of extracts of primary cultures of oPT using an antiserum against CREB,
      revealed a major band of CREB-ir at 44 KDa. The intensity of this band did not
      vary systematically with treatment. In extracts from untreated cells, Western
      blot analysis revealed a major band of pCREB-ir at 42 KDa which was not sensitive
      to agonist treatment. Treatment of cells with forskolin (10(-6) M) increased the
      intensity of a number of other pCREB-ir bands at between ca. 38 and 44 KDa. The
      band at 44 KDa probably represented native pCREB whilst the other bands induced
      by forskolin probably represented pCREB-like proteins. Melatonin (10(-6) M) alone
      had no effect on pCREB-ir, but it did inhibit the effect of forskolin on the ca.
      38 and 44 KDa pCREB-ir bands. Treatment with lamb serum (1%) consistently
      increased the intensity of the ca. 38 and 44 KDa pCREB-ir bands relative to
      control cells, as assessed by Western blot. However, Western blot analysis did
      not reveal a consistent effect of melatonin on the pCREB-ir response to serum.
      The effect of serum on pCREB-ir in oPT cells was characterized further by
      immunocytochemical analysis. In contrast to experiments utilizing Western
      blotting, untreated cells did not possess detectable pCREB-ir. In serum-starved
      oPT and oPD cultures, treatment with serum induced exclusively nuclear pCREB-ir.
      A large majority of oPT cells (> or = 90%) were sensitive to serum (1%), and
      serum caused a time- and dose-dependent increase of nuclear pCREB-ir. Melatonin
      attenuated the response to serum in the oPT. This inhibition of the response to
      serum was not apparent in the oPD, demonstrating that the effect of melatonin was
      specific for a tissue known to express melatonin receptors. In oPT cultures,
      physiological concentrations of melatonin (10(-9) M) partially reversed (ca. 70%)
      the inductive effect of 0.1% serum on nuclear pCREB-ir. However, in contrast to
      studies applying forskolin, the induction of pCREB-ir by serum occurred in the
      absence of measurable changes in the concentration of cyclic AMP, indicating that
      components of serum are able to stimulate the phosphorylation of CREB in the oPT
      through mechanisms independent of cyclic AMP. Both adenosine and prostaglandin E2
      (PGE2) also induced nuclear pCREB-ir in the absence of increased levels of cyclic
      AMP. These results demonstrate that transcriptional activities in the oPT which
      are under the control of CREB may be modulated by convergent cyclic AMP-dependent
      and cyclic AMP-independent pathways. Regulation of these pathways by melatonin
      and other factors present in serum may be an important control-point in the
      generation of seasonal neuroendocrine cycles.

PMID- 8866254
TI  - Purification and properties of alpha-amino-beta-carboxymuconate-epsilon
      semialdehyde decarboxylase (ACMSD), key enzyme of niacin synthesis from
      tryptophan, from hog kidney.
AB  - alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) (EC
      4.1.1.45) was purified to a homogeneous state from hog kidney cytosol by ammonium
      sulfate fractionation, Butyl-Toyopearl 650, hydroxyapatite, DEAE-Sephadex,
      Toyopearl HW55, Superdex 200 and TSK-gel G3000SW chromatographies. The molecular
      weight of the enzyme was estimated to be 58,000 by TSK-gel G3000SW gel
      filtration. The optimum pH (constant concentration) was 7.5. The Km for alpha
      amino-beta-carboxymuconate-epsilon-semialdehyde was 1.61 x 10(-5) M. The activity
      of purified enzyme was inhibited by some chemical modifying reagents such as
      monoiodoacetic acid and p-(chloromercuri) benzoic acid. A sulfhydryl group was
      deduced to exist in the active site of the enzyme.

PMID- 8866253
TI  - Acute immobilization stress and intraventricular injection of CRF suppress
      naloxone-induced LH release in ovariectomized estrogen-primed rats.
AB  - The present study was undertaken to evaluate the role and possible interaction of
      the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in
      the acute stress-induced suppression of gonadotropin secretion in ovariectomized
      estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20
      mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH)
      levels within 10 min in non-stressed animals. The naloxone-induced LH release was
      completely eliminated when tested 30 min after the onset of acute immobilization.
      In a subsequent study, it was found that suppression of the naloxone-induced LH
      release occurred as early as 5 min after the stress onset, and was still evident
      60 min after the end of a 30-min period of immobilization. The effect of naloxone
      was restored 3 h after liberation of the animal from the 30-min immobilization.
      An intraventricular (i.c.v.) injection of CRF (1 or 5 micrograms) also
      significantly suppressed, in a dose-related manner, the effect of a subsequent
      i.v. injection of naloxone. However, an i.c.v. injection of alpha-helical CRF(9
      41) (25 or 50 micrograms), a CRF antagonist, prior to immobilization, could not
      interfere with the suppressive effect of stress on naloxone-induced LH release.
      These results suggest that both acute immobilization stress and CRF can inhibit
      the LH secretory activity without mediation by EOP neurons. However, the stress
      related suppression may involve non-CRF mechanism(s).

PMID- 8866255
TI  - Feeding of excessive cystine and cysteine enhances defects of dietary copper
      deficiency in rats by differential mechanisms involving altered iron status.
AB  - We have reported that excess cystine feeding exaggerates the defects of dietary
      copper deficiency in rats by a mechanism not involving oxidative stress and
      altered copper status. This study was conducted to examine whether this
      exacerbation is caused by a mechanism involving altered iron status and to
      compare the influences of cystine and cysteine feeding on the defects of copper
      deficiency. Male Wistar rats were fed copper-adequate or copper-deficient diet
      with supplementation of L-cystine or L-cysteine (2%) for 10 days or 21 days.
      Copper-deficient diet increased heart weight, caused anemia, reduced plasma iron
      and elevated liver iron. These defects were exacerbated by supplemental cystine.
      Cysteine feeding also exacerbated the defects of dietary copper deficiency
      including anemia, increased heart weight, and reduced plasma iron, although
      cysteine feeding had no influence on liver iron concentration. Supplemental
      cysteine reduced apparent absorption of iron, while supplemental cystine did not.
      These results suggest that cystine feeding enhances the defects of copper
      deficiency by a mechanism involving impaired mobilization of iron from liver into
      blood, and that cysteine feeding enhances the defects of copper deficiency by a
      mechanism involving reduced intestinal absorption of iron.

PMID- 8866256
TI  - An assessment of docosahexaenoic acid (DHA) intake with special reference to
      lipid metabolism in rats.
AB  - In order to determine the appropriate intake of docosahexaenoic acid (22:6n-3,
      DHA), the potential changes in lipid peroxidation and antioxidant defense in
      serum and tissue as well as the changes in serum lipid levels were examined in
      rats by giving them diets containing graded levels of purified DHA (0, 1.0, 3.4
      and 8.7 energy % in the diets) for 2 weeks. Serum alpha-tocopherol concentration
      decreased slightly but significantly even at the 1.0 energy %. Liver lipid
      peroxide levels as assessed by the thiobarbituric acid (TBA) value and
      chemiluminescence intensity augmented at the 3.4 energy % and more, and the alpha
      tocopherol content significantly decreased in response to the increase in lipid
      peroxide levels. In the kidney, a slight but significant increase in TBA value
      was observed even at 1.0 energy % and higher. All the serum lipid levels as
      analyzed by total cholesterol, HDL-cholesterol, triacylglycerol (TG) and
      phospholipids (PLs) decreased as the dietary DHA level increased. These
      experimental results suggest that the dietary intake of DHA should be less than 1
      energy % to avoid promoting deleterious influences such as serum and tissue lipid
      peroxidation and to ameliorate serum lipid levels.

PMID- 8866257
TI  - Levels of pulmonary surfactant protein A in fetal lung and amniotic fluid from
      protein-malnourished pregnant rats.
AB  - Surfactant protein A (SP-A) is a major apo-protein of pulmonary surfactant, which
      lines the alveolar walls, lowering the surface tension to prevent lung collapse.
      Pregnant rats were divided into two groups which received a diet with either 5%
      or 20% protein from gestational day 9. By a sensitive immunoassay, SP-A levels in
      the fetal lungs and the amniotic fluid showed a dramatic increase with advancing
      gestation after the initial appearance on gestational day 18 in both diet groups.
      Significantly lower levels of SP-A in pregnant rats fed 5% protein diet than
      those in pregnant rats fed 20% protein diet were observed in the fetal lungs on
      gestational day 21 and in the amniotic fluid on gestational days 20 and 21. The
      profiles of increased SP-A levels in the amniotic fluid reflected those in the
      fetal lungs during gestation. Immunohistochemical examination with anti-rat SP-A
      antibody at 21 days of gestation showed that the immunoreactive staining of
      bronchiolar epithelial Clara cells and alveolar type II cells were weaker in the
      fetal lung sections from pregnant rats fed 5% protein diet than in those from
      pregnant rats fed 20% protein diet. It is concluded that protein malnutrition in
      pregnant rats affects the biosynthesis of SP-A in the fetal lungs, which may have
      important consequences for prematurity and decreased respiratory functions in the
      neonatal lungs at birth.

PMID- 8866258
TI  - Preparation of corn peptide from corn gluten meal and its administration effect
      on alcohol metabolism in stroke-prone spontaneously hypertensive rats.
AB  - Corn peptide (CP) was prepared from corn gluten meal by proteolysis with alkaline
      protease from alkalophilic Bacillus A-7. Free amino acids were not found in the
      CP product. Gel filtration on a Shodex OH-packed column revealed that the
      molecular weight distribution of the CP was less than about 2,000, characteristic
      of dipeptides to decapeptides, i.e. oligopeptides. The amino acid pattern of CP
      was similar to that of corn gluten meal, which was rich in alanine and branched
      chain amino acids, but poor in basic amino acids. The effect of the CP
      administration on alcohol metabolism was examined with SHR-SP, which were given
      ethanol orally through a gastric tube at the rate of 1.0 g/kg. Prior
      administration of CP at 1.0 g/kg resulted in fast disappearance of ethanol and
      its oxidative product acetaldehyde from the blood relative to the control without
      administration. Hence, it is suggested that CP, rather than its constituent amino
      acids such as alanine and proline, effectively takes part in enhancing the
      metabolism of ethanol as well as acetaldehyde.

PMID- 8866259
TI  - Bioavailability and stability of microencapsulated ferrous sulfate in fluid milk:
      studies in mice.
AB  - Iron deficiency is the most important nutritional problem all over the world.
      Fluid milk is an attractive vehicle for iron fortification, since it is a food
      with a high nutritional value, accessible to the whole population and easy to be
      given to children. Fortification of this food with iron has the disadvantage of
      the interaction of the iron with the constitutive elements of milk, diminishing
      its bioavailability and changing its sensorial properties, making it
      unacceptable. Nowadays, this problem can be overcome by the implementation of a
      new technological procedure, which consists in the microencapsulation of the
      ferrous sulfate with lecithin, thus avoiding the interaction of iron with the
      food. The absorption obtained in mice for milk-ferrous sulfate was 7.9 +/- 3.2%,
      while for microencapsulated ferrous sulfate-milk the result was 11.6 +/- 4.5%.
      Comparing these data with those obtained with the ferrous ascorbate in water 13.1
      +/- 4.9% and ferrous sulfate in water 13.2 +/- 4.3%, both of them considered as
      reference standards, no statistically significant difference between them and the
      microencapsulated ferrous sulfate in milk can be observed. However, this
      difference becomes significant (p < 0.01) when these products are compared to the
      non-encapsulated ferrous sulfate in milk. On the other hand, we demonstrated that
      this product is stable to heat-processing (100 degrees C, 30 min) and storage at
      a room temperature up to 6 months that lacteous products are usually submitted
      to.

PMID- 8866260
TI  - Energy and nutrient intakes of Okinawan centenarians.
AB  - Energy and nutrient requirements of younger people have been well studied, unlike
      that of centenarians. The average life span of the Japanese is the longest in the
      world, and the population of the very aged is rapidly growing. In addition, the
      average life span of Okinawan people is the longest in all of Japan. Their food
      habits also differ from other parts of Japan. To obtain basic dietary
      information, we surveyed 21 centenarians in Okinawa (17 women and 4 men). The
      dietary survey was done by one 24 h recall method, as was done for centenarians
      living throughout Japan (3). The energy intake of the Okinawan centenarians
      living at home was about 1,100 kcal/day for both sexes, which was similar to that
      of centenarians throughout Japan. Energy, some nutrient intakes and food
      consumption pattern (in terms of food groups) were different from those of the
      centenarians throughout Japan. We also measured their heights, weights,
      hematological values and activities of daily living (ADL). Comparison between the
      nutrient intakes and the recommended dietary allowances (RDAs) estimated for the
      centenarians showed that the estimated RDA of energy for the Okinawan
      centenarians might be less than their actual intakes.

PMID- 8866261
TI  - Capsaicin in diet does not affect glycogen contents in the liver and skeletal
      muscle of rats before and after exercise.
AB  - Effects of capsaicin, a pungent principle of hot red pepper, on glycogen contents
      in the liver and skeletal muscle at rest and during exercise were studied in
      rats. The contents of glycogen in the liver and soleus muscle, and the
      concentrations of serum glucose, lactate, free fatty acid and glycerol were
      examined. Capsaicin was supplemented at 0.014% of the experimental diet. Each
      group of rats was fed the capsaicin-diet ad libitum for 7 days, and then both
      groups of rats were fed isoenergetic diets with or without capsaicin for 7 days.
      Rats were trained running with a treadmill for 14 days. At the final stage of the
      experiments, 1 h running was loaded after the capsaicin diet or the control diet.
      The glycogen contents in the liver and soleus muscle were not significantly
      different between the capsaicin-diet group and the control-diet group after the
      meal and during exercise. The concentrations of serum glucose, lactate, free
      fatty acid and glycerol were not significantly different between the two dietary
      groups after the meal and during exercise. The results in this study suggest that
      the intake of capsaicin have little effect on glycogen contents in the liver and
      soleus muscle at rest and during exercise in rats previously fed a capsaicin-diet
      ad libitum for 1 week.

PMID- 8866262
TI  - Secondary caries formation in vitro around glass ionomer-lined amalgam and
      composite restorations.
AB  - The aim of this in vitro secondary caries study was to examine the glass-ionomer
      liner's effect on wall-lesion inhibition when a conventional and a light-cured
      glass ionomer liner was placed under amalgam and composite resin restorations.
      Class V preparations in extracted upper premolars were used and ten restorations
      were used for each of the following groups: (i) two layers of copal varnish and
      amalgam; (ii) conventional glass-ionomer and amalgam; (iii) light-cured glass
      ionomer and amalgam; (iv) bonding agent and light-cured composite resin; (v)
      conventional glass-ionomer, bonding agent and light-cured composite resin; (vi)
      light-cured glass-ionomer, extended 0.3 mm short of the enamel margin bonding
      agent and light-cured composite resin; and (vii) light-cured glass-ionomer,
      extended 1 mm short of the enamel margin, bonding agent and light-cured composite
      resin. The teeth were thermocycled and artificial caries were created using an
      acid-gel. The results of this study showed that artificial recurrent caries can
      be reduced significantly (P < 0.05) with a glass-ionomer liner under amalgam
      restorations. The results also showed that when the light-cured glass-ionomer
      liner was placed 0.3 mm from the cavosurface margin under composite resin
      restoration, the artificial recurrent caries reduced significantly (P < 0.05).

PMID- 8866263
TI  - Frequency of edentulism and identification marking of removable dentures in long
      term care units.
AB  - There were two aims of this study. First, the frequency of edentulism and denture
      wearers among 464 residents in long-term units in Goteborg, Sweden, was
      evaluated. Second, the dentures were examined to determine whether they were
      marked correctly for identification. Of the subjects, 46% were edentulous in both
      jaws, and 13% in one jaw. Among complete denture wearers, 47% of the patients had
      at least one identification-marked denture. Removable partial dentures, worn by
      26 subjects, were marked to a lesser extent (32%). Since there are many
      edentulous people among the elderly in most parts of the world we suggest that
      removable dentures are marked with the patient's name or identification number.

PMID- 8866264
TI  - Fracture surface characteristics of damaged acrylic-resin-based dentures as
      analysed by SEM-replica technique.
AB  - The aim of this study was to determine some characteristics of the fracture
      surface of an acrylic resin denture. For this purpose, five complete upper
      dentures and two complete lower dentures that had fractured into two pieces were
      collected, the fracture surfaces were duplicated with the SEM-replica technique
      and duplicated surfaces were investigated with a scanning electron microscope.
      The reproducibility of the SEM-replica technique was tested by comparing one
      original sample surface and its replica surface of the same area. The SEM
      photomicrographs revealed a series of fine striations in the fracture surfaces of
      both the upper and lower dentures perpendicularly orientated to the direction of
      the fracture propagation. A smooth area on the fracture surface was assumed to
      indicate a slow fatigue fracture process, and a rougher area fracturing with
      increased velocity.

PMID- 8866265
TI  - A computerized method for evaluating balance of occlusal load.
AB  - In order to undertake a quantitative evaluation of balance occlusal load, the use
      of the Dental Prescale System was investigated. The method uses a test sheet that
      undergoes a colour-developing chemical reaction, for detecting contact area, and
      a computerized analysis system, for evaluating the balance of occlusal load.
      Twenty natural dentate subjects and 10 hemimaxillectomy patients participated in
      the study. Each subject bit a test sheet as hard as possible for 3 s. The balance
      of occlusal load was expressed as a percentage of the load on the side with the
      lesser occlusive load (%OLR). The %OLR ranged from 39.7% to 49.4% in the natural
      dentate subjects, and from 0% to 31.3% in the hemimaxillectomy patients at their
      resection site. The patients' low %OLRs were attributed to loss of sustaining
      structure and subjective occlusal adjustment by clinicians. Combining technical
      simplicity, relatively high reproducibility, and diverse analysis capability,
      this system is useful for quantitative evaluation of balance of occlusal load in
      clinical situations.

PMID- 8866266
TI  - Age changes in the rat temporomandibular joint articular disc: a biochemical
      study on glycosaminoglycan content.
AB  - The temporomandibular joint (TMJ) articular discs were removed from female
      Sprague-Dawley rats 3, 5, 10, 32, 90 and 130 weeks of age. Glycosaminoglycans
      (GAGs) were extracted from the discs by heat treatment, alkali treatment and
      digestion with Pronase E, and purified by precipitation with cetylpyridinium
      chloride and ethanol. The concentration of total GAG was highest in the 3 week
      extracts and tended to decrease with age. Dermatan sulphate was the predominant
      GAG detected in all age groups along with chondroitin sulphate, hyaluronic acid
      and heparan sulphate. The disaccharides obtained from chondroitin sulphate were
      delta Di-4S, delta Di-6S and delta Di-0S, with delta Di-4S being the predominant
      isomer followed by delta Di-6S for all ages of all the GAG examined. The
      concentration of chondroitin sulphate showed a decrease with age. Quantitative
      changes of GAG with age may be related to functional changes in TMJ discs.

PMID- 8866267
TI  - Diagnosis and mode of treatment for 'pseudo'-Class III patients and its effects
      on masticatory movements.
AB  - This paper describes the treatment and functional analysis of 18 'pseudo'-class
      III patients. Clinical examination revealed IC-RC discrepancies, aesthetic
      aberrations and functional disturbances. The improvement of these parameters upon
      treatment was followed by sirognathographic recordings.

PMID- 8866268
TI  - Relationship between condylar and incisor point displacement during habitual
      maximum open-close movements.
AB  - The relationship between condylar movements and incisor point movements during
      habitual maximum open-close movements were studied in 10 healthy male and 10
      healthy female subjects. Jaw movements were recorded by means of an opto
      electronic jaw movement recording system, OKAS-3D, capable of recording the six
      degrees of freedom at a sample frequency of 300 Hz. The lower jaw position of the
      lateral pole of the condyles was found by means of palpation. In order to analyse
      the movements, the opening and closing path of the incisor point were divided
      into ten equal intervals and the corresponding condylar displacement in each
      interval was calculated. A displacement index was obtained by normalizing the
      condylar displacement with respect to the maximum condylar displacement. Due to
      the normalization, the displacement index is not sensitive to possible errors in
      the location of the lateral condylar point. A clear condylar displacement was
      already recorded in the first movement interval, right at the start of opening
      (average displacement index in the first opening interval was significantly
      greater than zero, P < 0.0005). The condylar displacements in the start and the
      end interval of opening and closing were smaller than in the intermediate
      movement intervals (P < 0.00005).

PMID- 8866269
TI  - In search of clinical excellence.
AB  - This article was presented as a lecture at the 1995 Combined Sections Meeting by
      Joseph P. Farrell, MS, PT, who received the Orthopaedic Section's Paris
      Distinguished Service Award. He was recognized for service to the Orthopaedic
      Section in the area of manual therapy and for the formation of the American
      Academy of Orthopaedic Manual Physical Therapists (AAOMPT). Clinical excellence
      is a journey that every clinician should commence early in his/her career. The
      purpose of this paper is to discuss clinical excellence and its importance to the
      physical therapy profession. To address this topic, the following items will be
      discussed: 1) clinical competency and clinical expertise; 2) communication and
      patient management in the current era of health care reform; 3) politics relating
      to manual therapy; 4) the role of manual therapy in our profession; 5) clinical
      residency educational programs; and 6) the academic and clinician role in
      education. The author concludes that if physical therapy is a profession of
      excellent clinicians, then the physical therapy profession can survive evolving
      changes in the health care system.

PMID- 8866270
TI  - Assessment of exercise-induced minor muscle lesions: the accuracy of Cyriax's
      diagnosis by selective tension paradigm.
AB  - The Cyriax selective tension assessment paradigm is commonly used by clinicians
      for the diagnosis of soft tissue lesions; however, studies have not demonstrated
      that it is a valid method. The purpose of this study was to examine the construct
      validity of the active motion, passive motion, resisted movement, and palpation
      components of the Cyriax selective tension diagnosis paradigm in subjects with an
      exercise-induced minor hamstring muscle lesion. Nine female subjects with a mean
      age of 23.6 years (SD = 4.7) and a mass of 57.3 kg (SD = 10.7) performed two sets
      of 20 maximal eccentric isokinetic knee flexor contractions designed to induce a
      minor muscle lesion of the hamstrings. Active range of motion, passive range of
      motion, knee extension end-feel pain relative to resistance sequence, knee flexor
      isometric strength, pain perception during knee flexor resisted movement testing,
      and palpation pain of the hamstrings were assessed at 0, 5, 2, 12, 24, 48, and 72
      hours postexercise and compared with Cyriax's hypothesized selective tension
      paradigm results. Consistent with Cyriax's paradigm, passive range of motion
      remained unchanged, and perceived pain of the hamstrings increased with
      resistance testing at 12, 24, 48, and 72 hours postexercise when compared with
      baseline. In addition, palpation pain of the hamstrings was significantly
      elevated at 48 and 72 hours after exercise (p < 0.05). In contrast of Cyriax's
      paradigm, active range of motion was significantly reduced over time (p < 0.05),
      with the least amount of motion compared to baseline (85%) occurring at 48 hours
      postexercise. Further, resisted movement testing found significant knee flexor
      isometric strength reductions over time (p < 0.05), with the greatest reductions
      (33%) occurring at 48 hours postexercise. According to Cyriax, when a minor
      muscle lesion is tested, it should be strong and painful; however, none of the
      postexercise time frames exhibited results that were strong and painful. This
      study suggests that the validity of using Cyriax's selective tension testing for
      the diagnosis of exercise-induced minor muscle lesions is questionable.

PMID- 8866271
TI  - The effects of pelvic movement on lumbar lordosis in the standing position.
AB  - The purpose of this study was to investigate whether the maneuver of altering the
      angle of pelvic tilt when standing is effective in changing the angle of lumbar
      lordosis. The importance of the study was to establish a scientific basis for a
      common clinical assumption. Pelvic tilt and lumbar lordosis were measured during
      three conditions: with subjects in a normal standing posture, with subjects
      assuming a maximal anterior pelvic tilt posture, and with subject assuming a
      maximal posterior pelvic tilt posture. Measurements of pelvic tilt and lumbar
      lordosis were obtained using a television/computer system that obtained the three
      dimensional coordinates of markers on the pelvis and spine at 20-msec intervals.
      Each measurement was made three times, and all were found to be reliable, with
      intraclass correlation coefficients (3,1) ranging from 0.78 to 0.95 (p < 0.001).
      Adopting a maximal anterior pelvic tilt changed the pelvic attitude relative to
      the horizontal by an average fo 11.4 degrees (p < 0.001) and increased the lumbar
      lordosis by an average of 10.8 degrees (p < 0.001). Adopting a maximal posterior
      pelvic tilt changed the pelvic attitude by an average of 8.7 degrees (p < 0.001)
      and decreased the lumbar lordosis by an average of 9.0 degrees (p < 0.001). The
      results of this study demonstrate that altering the pelvic tilt significantly
      changes the angle of lumbar lordosis. This lends support to the use of pelvic
      tilting exercises to increase or decrease the degree of lumbar lordosis, at least
      for the duration of the exercise.

PMID- 8866272
TI  - A comparison of closed kinetic chain and isokinetic joint isolation exercise in
      patients with patellofemoral dysfunction.
AB  - Recently, there has been attention to the clinical application of closed kinetic
      chain and joint isolation exercise. Our purpose was to compare the effect of
      joint isolation and closed kinetic chain exercise on quadriceps muscle
      performance and perceived function in patients with patellofemoral pain. Twenty
      three patients participated in an 8-week training period and were assigned to
      either a closed kinetic chain or a joint isolation exercise training group. An 8
      inch (20.3 cm) retro step-up test was performed at baseline, 8 weeks, and 1 year.
      Seated knee extension testing was measured at baseline and at 8 weeks using peak
      concentric torque on an isokinetic dynamometer at 90 degrees/sec, 180
      degrees/sec, and 360 degrees/sec. Perceived functional status was rated as
      excellent, good, fair, or poor based on questionnaire response. Statistical
      analysis showed that both groups had significant improvement in peak torque at
      all speeds, but only the closed kinetic chain group showed significant
      improvement in closed kinetic chain testing and perceived functional status. We
      concluded that closed kinetic chain training may be more effective than joint
      isolation exercise in restoring function in patients with patellofemoral
      dysfunction.

PMID- 8866273
TI  - Method-related variations in estimates of gravity correction values using
      electromechanical dynamometry: a knee extension study.
AB  - Dynamometry is widely used to measure subject strength. The method employed to
      correct dynamometry scores for gravitational influences can result in differing
      correction estimates. This study investigates differences between mathematical
      estimates of correction values and directly measured passive forces. Using the
      Kin-Com dynamometer, passive force measurements from 90 degrees of knee flexion
      to full extension were collected for nine asymptomatic subjects. These
      measurements were then compared with correction estimates mathematically
      extrapolated from a force reading obtained at one point in the test range. Direct
      passive measurements obtained between 0 and 70 degrees of knee flexion and
      mathematical estimates of correction values differed by as much as 50 N. The
      equivalence of gravity correction values obtained using the two methods detailed
      cannot be assumed. Mathematical estimates of correction values for knee scores
      obtained between 0 and 90 degrees of flexion were found to be clinically
      identical to direct passive measurements when: 1) the limb was weighed close to
      50 degrees of flexion and 2) the angular location of the lower limb mass relative
      to the horizontal was not assumed to be represented by the angular location of
      the lever arm, but rather 15 degrees further below the horizontal than the lever
      arm.

PMID- 8866274
TI  - Assessment of quadriceps muscle performance by hand-held, isometric, and
      isokinetic dynamometry in patients with knee dysfunction.
AB  - One component of patient evaluation is muscle performance assessment. The purpose
      of this study was: 1) to determine the difference and correlation between hand
      held, isometric, and isokinetic dynamometry test results in patients with knee
      dysfunction and 2) to determine the effect of pain during such testing. Bilateral
      quadriceps strength in 23 subjects with unilateral knee dysfunction was tested
      using concentric and eccentric isokinetic dynamometry at 60 degrees/sec,
      isometric dynamometry, and hand-held dynamometry, both at 60 degrees of knee
      flexion. Pain ratings were obtained before, during, and after each test.
      Statistical analysis revealed a significant difference between involved and
      uninvolved limbs for eccentric isokinetic dynamometry (p = 0.002) and hand-held
      dynamometry (p = 0.005); no difference was found between limbs for the concentric
      isokinetic and isometric dynamometry (p > 0.05). Mean percent deficits in
      quadriceps strength ranged from 11 to 18%, with no significant difference found
      between testing modes. Pearson product moment correlations ranged from 0.34 to
      0.76 when comparing testing modes. No significant difference existed in pain
      scores before, during, and after each mode of testing. It was concluded that
      large variation existed between different testing modes, which results in
      different conclusions regarding the strength of the quadriceps in patients with
      knee dysfunction.

PMID- 8866275
TI  - Reflex response times of vastus medialis oblique and vastus lateralis in normal
      subjects and in subjects with patellofemoral pain syndrome.
AB  - Various authors have indicated that imbalance of the vastus medialis/vastus
      lateralis muscles might lead to patellofemoral pain syndrome. However, few
      reports have been published to substantiate such a hypothesis. The purpose of
      this study was to attempt to set a scale for the normal reflex response times of
      the vastus medialis oblique and vastus lateralis muscles after a patellar tendon
      tap and to determine if patellofemoral pain syndrome patients have an alteration
      in this firing sequence. A control group of 80 healthy adults was compared with a
      group of 19 patellofemoral pain syndrome patients. Results indicated that the
      reflex response time of the vastus medialis oblique was significantly shorter
      than the reflex response time of the vastus lateralis in the normal subjects (p <
      or = .01). When comparing these data in the patellofemoral pain syndrome group, a
      significant earlier firing was obtained from the vastus lateralis in comparison
      with the vastus medialis oblique (p < or = .01). These findings suggest that a
      reversal has occurred in the firing pattern of the vastus medialis oblique and
      vastus lateralis muscles in patellofemoral pain syndrome patients. The results
      indicate an alteration in the neuromuscular answer of the vastus medialis oblique
      and vastus lateralis muscles during a patellar tendon tap.

PMID- 8866276
TI  - Prevention of secondary coxarthrosis in slipped capital femoral epiphysis: a long
      term follow-up study after corrective intertrochanteric osteotomy.
AB  - Fifty-one patients with unilateral severe (gliding angles 30 degrees-60 degrees)
      slipped capital femoral epiphysis (SCFE) treated by intertrochanteric corrective
      osteotomy were reexamined after 20-29 years (average 24 years) of follow-up; 55%
      of the patients showed neither radiographic signs of degenerative hip disease nor
      clinical symptoms, whereas 28% had moderate and 17% had severe osteoarthritis.
      These results are definitely superior to those reported in other series of
      patients with comparable slips treated by bed rest or in situ fixation only.
      Analysis of individual gliding angles and directions of the slips shows that
      results can probably be further improved by correct assessment of the gliding
      process to allow for best use of the potentials of intertrochanteric corrective
      osteotomies. Correction should also be performed as early as possible to allow
      for maximum remodeling.

PMID- 8866277
TI  - Loss of hip motion in slipped capital femoral epiphysis: a calculation from the
      slipping angle and the slope.
AB  - The range of hip motion in 128 hips of 108 patients was measured at an average of
      32.7 years after slipping of the capital femoral epiphysis (SCFE). Only hips
      without signs of osteoarthrosis were selected for the study. The hips were
      divided into three groups depending on treatment (i.e., fixation in situ, no
      treatment, osteotomy) and compared with those of a group with no slipping (normal
      hip). The slipping angle (SA) between the basis of the epiphysis and the
      perpendicular to the anteversion plane on lateral radiographs and the slope (S)
      between the basis of the epiphysis and the perpendicular to the axis of the femur
      on anteroposterior (AP) radiographs were measured. The only significant loss of
      hip motion evident in comparison of normal hips and hips with previous SCFE, was
      loss of external rotation in hips treated with osteotomy. Hips with no treatment
      and hips treated with fixation in situ showed no significant loss of hip motion
      as compared with normal hips. The greatest loss of hip motion in hips treated
      with fixation in situ was loss of internal rotation (LIR), which can be
      calculated using the radiographs as sin LIR = sin SA * sin S. The average
      difference between clinically established and calculated LIR was 1.15 degrees. We
      conclude that the loss of hip motion after SCFE is slight and in most patients
      not clinically relevant. Therefore, early surgical intervention, e.g., femoral
      osteotomy, due to expected loss of hip motion cannot be justified.

PMID- 8866278
TI  - Slipped capital femoral epiphysis: a long-term follow-up, with special emphasis
      on the capacities for remodeling.
AB  - We reviewed 59 hips in 44 children with slipped capital femoral epiphysis (SCFE),
      all treated by in situ pinning. The average clinical and radiographic follow-up
      was 11.4 years. Fifty-three hips (90%) were rated as either excellent or good.
      Osteonecrosis or chondrolysis developed in five patients. Postoperative
      remodeling was noted, not only by a process of local resorption and apposition of
      bone, but also by correction of the disturbed anatomic axes, in proportion to the
      severity of the slip, together with global thickening of the femoral neck. We
      believe that the good long-term results after in situ pinning are the consequence
      of this important remodeling process.

PMID- 8866279
TI  - The contralateral hip in slipped capital femoral epiphysis.
AB  - The risk of contralateral slipping in slipped capital femoral epiphysis (SCFE)
      has been estimated to be 40-80% in follow-up examinations. Before age 50 years,
      25% of the contralateral hips with untreated slipping showed arthrosis, some
      severe. In the same long-term follow-up, no hip with mild or moderate slipping
      treated with pinning in situ had developed severe arthrosis at that age,
      indicating the risk of arthrosis in the contralateral hip in SCFE can be reduced
      by prophylactic pinning. Prophylactic pinning also diminishes the need for
      repeated radiographical examination during the remaining growth period. Provided
      that a technique with a low complication rate is used, prophylactic pinning of
      the contralateral hip is recommended in all cases of SCFE.

PMID- 8866280
TI  - Chondrolysis and avascular necrosis: complications of slipped capital femoral
      epiphysis.
AB  - Chondrolysis and avascular necrosis (AVN) are serious complications after slipped
      capital femoral epiphysis (SCFE). Chondrolysis, or acute cartilage necrosis of
      the capital femoral epiphysis, can occur in treated and untreated SCFE. Its exact
      etiology has not been conclusively determined, and there may be some connection
      with hardware penetration into the joint and its development. Because
      chondrolysis can occur in both treated and untreated hips, an immune mechanism
      has been postulated. Although some evidence of immune reaction has been confirmed
      in the joint, no screening test has yet been developed to determine susceptible
      individuals. AVN is clearly related to impeded blood supply to the femoral head
      and to severely slipped unstable acute slips. Forceful reduction of the femoral
      head must be avoided. However, some slips are so unstable that reductions occur
      merely with positioning of the patient for operation. Improperly placed fixation
      devices may also play a role in the development of AVN. Chondrolysis and AVN may
      not be completely avoidable in the treatment of SCFE.

PMID- 8866281
TI  - Chondrolysis after slipped capital femoral epiphysis.
AB  - Chondrolysis, or acute cartilage necrosis, is a controversial and perplexing
      complication of slipped capital femoral epiphysis (SCFE) in adolescents. It
      usually leads to deformity, pain, limping, and limitation of motion in the
      affected extremity. Although several theories have been proposed, no agreement
      has been reached as to the etiology or the pathogenesis of chondrolysis.
      Furthermore, no treatment program has been completely successful, and the general
      prognosis and natural history of this condition are not clear. An overview of the
      latest knowledge of the matter is presented.

PMID- 8866282
TI  - Orthopaedic treatment and passive motion machine: consequences for the surgical
      treatment of clubfoot.
AB  - The efficacy of orthopaedic treatment and its influence on clubfoot surgery has
      never been truly demonstrated. In the unsorted mass of clubfeet treated, it is
      difficult to determine exactly how effective orthopaedic treatment is for
      severely affected feet. If properly performed, perfectly synchronized, and
      supported by a Kinetec machine, such treatment can noticeably reduce the rate of
      operation and, when operation is still required, reduce its extent. In grade II
      soft > stiff feet with scores of 5-10, Kinetec-supported orthopaedic treatment is
      extremely effective. Operation is required in 32% of cases only, and posterior
      surgery is often sufficient. Lateral release, in this category, is never
      required. In grade III stiff > soft feet, with scores of 10-15, the efficacy of
      orthopaedic treatment associated with the Kinetec machine is far from negligible
      and operation most often includes posterior and medial release (PMR), variably
      associated with plantar release. Lateral release is exceptional (15%), and
      operation is necessary in 75% of cases. In grade IV stiff = stiff feet, with
      scores of 15-20, orthopaedic treatment with the Kinetec machine has a true,
      though limited, effect. In this category, operation is necessary in 90% of cases.
      Lateral release is performed in 50%. In the postoperative period, orthopaedic
      treatment combined with use of the Kinetic machine must be continued. Orthopaedic
      treatment coordinated with use of the machine has considerably shortened the
      duration of plaster cast immobilization; 2 months when operation included
      posterolateral-medial (PLMR) release or PMR, and only 1 month when operation was
      posterior release (PR). The machine has noticeably changed the results and has
      indisputably influenced operation on the whole.

PMID- 8866283
TI  - Growth in 110 children with Legg-Calve-Perthes' disease: a longitudinal infancy
      childhood puberty growth model study.
AB  - Growth in 110 children with Legg-Calve-Perthes' disease (LCPD) was longitudinally
      followed throughout the growth period. The infancy childhood puberty (ICP) growth
      model, which has the advantage that reference values can be adjusted for the
      individual age at pubertal maturation, was used. On the average, the children
      were slightly shorter at birth and they remained short throughout the entire
      growth period to maturity. At maturity, the boys were 4.4 cm and the girls were
      2.5 cm below the reference mean. The growth velocity was normal at the time of
      diagnosis, prepubertally, and during puberty. Boys and girls differed only in
      that the boys were more overweight.

PMID- 8866284
TI  - Juvenile progressive scoliosis and congenital horizontal gaze palsy.
AB  - Eleven articles reporting 39 patients with the combination of progressive
      scoliosis and familial congenital gaze palsy have now been published. This
      disorder appears to be caused by a malfunction of the normal equilibrial control
      mechanism related to the brainstem or the central nervous system. The scoliosis
      progresses when the children begin to walk. Even when they are treated with
      physiotherapy or brace, they often require early operation. We consider that
      progressive juvenile or infant scoliosis associated with familiar congenital
      horizontal gaze palsy constitutes a clinical entity. We report two sisters with
      congenital gaze palsy, in one of whom scoliosis of at least 70 degrees (Cobb)
      developed, and review and analyze all cases published until now.

PMID- 8866285
TI  - Results of a trial of anterior or circumferential lumbar fusion in the treatment
      of severe isthmic spondylolisthesis in young patients.
AB  - The radiological and clinical results in 27 patients operated on for severe
      isthmic spondylolisthesis at age < 20 years with uninstrumented anterior
      interbody fusion alone in 11 or combined anterior and posterolateral
      (circumferential) fusion in 16 are reported. The mean follow-up time was 5.9 +/-
      2.4 years. The two groups were comparable with regard to age at operation, sex,
      preoperative symptoms, mean preoperative slip and sagittal rotation angle. The
      follow-up assessment, made by an independent observer, included interview,
      Oswestry disability index, physical examination, functional tests, and plain
      radiographs. At follow-up, there were no statistical differences between the
      groups in subjective, clinical, and functional outcomes. Follow-up radiographs
      showed no progression of slip in either group. The sagittal rotation angle
      worsened slightly in the anterior fusion group but improved by 5.8 degrees (p <
      0.001) on the average in the combined fusion group. There were no instances of
      pseudarthrosis. Two patients, one in each group, were reoperated on early for
      postoperative peroneal weakness; both recovered. The clinical and functional
      results were satisfactory in most cases. The radiological results concerning the
      sagittal rotation angle were superior in the combined fusion group, but whether
      this will affect the long-term clinical result is not known.

PMID- 8866286
TI  - Internal fixation of femoral shaft fractures in children and adolescents: a ten-
      to twenty-one-year follow-up of 52 fractures.
AB  - In a long-term follow-up (mean 16 years) of 52 femoral shaft fractures treated by
      internal fixation in 50 children and adolescents, we noted a mean overgrowth of 1
      mm after plating and a mean undergrowth or relative shortening of 2 and 9 mm
      after nailing with broad (IMN) and slender (flexible rods: IMR) intramedullary
      nails, respectively. The mean overgrowth was 8 mm in children, but adolescents
      had a mean undergrowth of 5 mm (p < 0.01). Excessive overgrowth tended to occur
      less frequently after intramedullary nailing than after plating (p = 0.1).
      Undergrowth tended to occur with increasing frequency with increasing age and
      attained troublesome levels in three patients with severe trauma. Three cases of
      moderate valgus deformity of the hip and one case of late arthrosis of the hip
      occurred after intramedullary nailing with IMN introduced through the greater
      trochanter. We conclude that this method should not be used in patients with open
      physes.

PMID- 8866287
TI  - Fractures of the radial head and associated elbow injuries in children.
AB  - Fractures of the radial head are frequently associated with elbow injuries in
      children. Thirty-seven patients with this association treated at the Nancy
      Children's Hospital were analyzed to ascertain the mechanism and the unfavorable
      factors of prognosis. The mechanism responsible was a valgus strain on the elbow
      at the moment of impact, associated with forces of compression and distraction.
      At an average follow-up of 2 years, 76% excellent and good results were obtained.
      Conservative treatment was always effective in minimally displaced fractures.
      With surgical reduction by closed intramedullary pinning (CIMP), there were only
      three failures in severely displaced fractures. With open reduction, results were
      always poor; 88% patients with fair and poor results had an associated fracture
      of the olecranon. The unfavorable prognostic factors were the severity of the
      initial tilting and displacement, the presence of associated elbow injuries, the
      inadequacy of reduction, and the open reduction procedure.

PMID- 8866288
TI  - Obstetric brachial plexus palsy.
AB  - In a retrospective survey of 46 conservatively treated patients with obstetric
      brachial plexus palsy (OBPP) the following conclusions were reached. An immediate
      examination of the neurological status of the neonate root by root is essential
      for proper analysis of the course of the recovery. Mild cases with C5-C6 root
      injury (Erb's palsy) have a good outcome and may be treated conservatively.
      Intermediate cases with C5-C7 root injury with additional drop hand require close
      observation as early as age 3 weeks when the first electromyographic (EMG)
      examination is indicated. The second EMG should be performed at age 11-12 weeks.
      If the function of the brachial biceps muscle is lacking at age approximately 12
      weeks (3 months), microsurgical intervention should be considered; such
      intervention definitely is required at age 5 months if the paresis in the
      brachial biceps muscle has not recovered. Severe cases with C5-C8 or C5-Th1 root
      injuries with flaccid abducted arm, wrist drop, claw hand, and possibly head tilt
      to the contralateral side and Horner's sign should be operated on primarily at
      age 1-2 months.

PMID- 8866289
TI  - Posttraumatic scoliosis.
AB  - A case of posttraumatic scoliosis due a misdiagnosed lumbosacral unilateral
      dislocation was observed 6 weeks after a traffic injury in a 15-year-old boy.
      Cobb angle was 30 degrees on T10-L4 with 20 degrees rotation on L1 and L2.
      Initial radiographs were normal. The scoliosis was corrected after surgical
      correction of the dislocation; at 5-year follow-up, the patient worked normally;
      there was no scoliosis. The suggested physiopathology of this structural
      scoliosis is similar to spondylolisthetic scoliosis of childhood in which
      asymmetrical forward displacement of the vertebral body results in rotational
      shift of the vertebra, with lumbar scoliosis. Correction of the scoliosis depends
      on correction of the lumbosacral dislocation.

PMID- 8866290
TI  - Hemimetatarsal transfer: a unique solution for postaxial metatarsal duplication.
AB  - Many operations have been described for the reconstructive treatment of foot
      congenital anomalies involving multiplication of toes and metatarsi. We describe
      a surgical procedure designed to solve the problem of postaxial polydactily with
      complete duplication of metatarsi. We successfully performed hemimetatarsal
      transposition of the hypoplastic metatarsal bone with its intact metatarso
      phalangial joint to the base of the extra metatarsus. We achieved good alignment
      of the lateral ray with restoration of the metatarsal weight-bearing touch
      points. Functional and cosmetic results of the procedure were excellent.

PMID- 8866291
TI  - Evaluation of neonatal whole blood versus plasma glucose concentration by ion
      selective electrode technology and comparison with two whole blood chromogen test
      strip methods.
AB  - OBJECTIVE: Determination of glucose concentration from whole blood samples in
      neonates is confounded by variable hematocrit values, sample source, user
      technique, and test method, which results in poor correlation with glucose values
      measured from plasma or serum. Recently developed ion-selective electrodes (ISE)
      allow measurement of glucose in the water phase of both red blood cells and
      plasma with a small sample size (200 microliters). STUDY DESIGN: The purpose of
      this study was to compare (1) whole blood and plasma glucose measurements by the
      ISE method and (2) ISE glucose values with those determined by two chromogen
      reagent test strip colorimetric methods. Values were determined in 180 different
      samples obtained from 145 infants. RESULTS: Correlation of whole blood and plasma
      glucose concentrations determined by the ISE method was excellent (y = 0.99x, R2
      = 0.99) and no effect was seen from hematocrit values. The two chromogen test
      strip methods also revealed good linearity with ISE whole blood and plasma
      glucose values but had large confidence intervals for individual values.
      Sensitivity for detecting blood glucose levels < 40 mg/dl by the two test strip
      methods was 9 of 11 and 9 of 10 with four and one false-positive results,
      respectively. CONCLUSION: These data indicate that the ISE method provides an
      excellent correlation of whole blood and plasma glucose measurement results,
      overcoming technical problems of differing hematocrit values and serum or plasma
      sample acquisition in neonates. Chromogen test strip methods have limited value
      in estimating specific glucose values, but can be useful in screening infants for
      hypoglycemia.

PMID- 8866292
TI  - Clinical utility of a glucose reflectance meter for screening neonates for
      hypoglycemia.
AB  - OBJECTIVE: The purpose of this study was to examine the clinical utility of a
      glucose reflectance meter to screen neonates for hypoglycemia. STUDY DESIGN: One
      hundred six infants admitted to the observation or level III nursery with a
      screening whole blood glucose concentration < or = 2.8 mmol/L (< or = 50 mg/dl)
      had a second sample drawn to compare glucose reflectance meter measurements with
      those of corrected laboratory-determined glucose concentrations. Error grid
      analysis was used to determine clinical utility of the reflectance meter in a
      clinical setting. RESULTS: No reading obtained with the glucose reflectance meter
      was > 2.2 mmol/L (40 mg/dl) in infants whose true whole blood glucose
      concentration was < or = 1.7 mmol/L (30 mg/dl). Only 0.9% (1/106) of glucose
      reflectance meter values were < or = 1.7 (< or = 30 mg/dl) when the simultaneous
      laboratory-determined whole-blood glucose concentration was > 2.2 mmol/L (40
      mg/dl). Glucose concentrations obtained by the reflectance meter correlated (r =
      0.77, p = 0.001) with laboratory-determined concentrations. CONCLUSION: The
      glucose reflectance meter provides a rapid and clinically useful method of
      screening for neonatal hypoglycemia.

PMID- 8866293
TI  - Advanced maternal age: perinatal outcome when controlling for physician
      selection.
AB  - OBJECTIVE: Our purpose was to determine whether differences in maternal outcome
      because of maternal age could be controlled by the elimination of bias in
      physician selection. STUDY DESIGN: We performed a case-control study that
      compared pregnancy outcomes of 164 patients delivered at our institution at > or
      = 40 years old with outcomes in a control group consisting of the next two
      deliveries by the same attending physician of women with ages 20 to 29 years.
      Retrospective analysis of the antepartum and intrapartum records was done to
      compare clinical outcome. RESULTS: We observed a significant increased incidence
      of nulliparous cesarean delivery (p = 0.046), elevated results of glucose screens
      with a 50 gm load (p = 0.00002), and hypertension throughout pregnancy in the
      older patients in spite of controlling for physician selection. The older patient
      group was more likely to have used assisted reproductive techniques (p =
      0.000005) and had higher baseline weights (p = 0.001) and maximum pregnancy
      weights (p = 0.042). However, the neonatal outcome was similar in both groups.
      Despite controlling for physician selection, we demonstrated increased rates of
      abdominal delivery, glucose intolerance, and hypertension in older patients.
      Fetal and neonatal outcomes were similar in both groups. CONCLUSION: Women > or =
      40 years old tend to have an increased incidence of a few pregnancy-related
      complications, even when controlling for physician selection.

PMID- 8866294
TI  - A comparison of the tympanic and axillary temperatures of the preterm and term
      infant.
AB  - A correlational research design was used to examine the accuracy between the
      axillary and tympanic temperature measurements of the preterm and term infant.
      Also examined was the effect of weight and environment on the temperature
      measurements. A convenience sample of 40 neonates (preterm, n = 20; term, n = 20)
      was selected. A correlation of 0.815 (p = 0.001) was found between the axillary
      and tympanic temperatures of all subjects, and correlations of 0.861 (p = 0.001)
      and 0.582 (p = 0.01) were revealed for the preterm and term infants,
      respectively. When weight was used as a covariate, there was no significant
      difference in the two temperature measurements by group (preterm, term), but
      there was a trend for tympanic temperatures, and the difference between axillary
      and tympanic temperatures, to differ by environment (radiant warmer, incubator,
      or open crib).

PMID- 8866295
TI  - Placental pathologic conditions in anticardiolipin antibody positive women whose
      infants had congenital heart defects.
AB  - Anticardiolipin antibodies (ACLA) are present in 10% of women with recurrent
      pregnancy loss. Other associations with ACLA are arterial and venous thrombosis,
      cerebral infarction, pulmonary hypertension, preterm delivery, and fetal growth
      retardation. A previous prospective study of infants of mothers with positive
      ACLA identified an increased incidence of congenital heart disease in this
      population. As a follow-up, the placentas of the initial 40 ACLA-positive
      patients were studied to determine whether there was an increased incidence of
      infarct or thrombosis compared with that in control subjects matched for maternal
      age and gestational age within the same 2-year period. The age of ACLA-positive
      mothers was 30 +/- 5 years versus 29 +/- 5 years in the ACLA-negative mothers.
      Gestational age was 37 +/- 2 weeks in both groups; placental weight was 553 +/-
      169 gm in the ACLA-positive group versus 593 +/- 117 gm in the ACLA-negative
      group. The birth weight was 2972 +/- 709 gm in infants of ACLA-positive mothers
      and 2920 +/- 674 gm in infants of ACLA-negative mothers. There was no
      statistically significant difference between the two groups in gestational age,
      maternal disease, placental histologic findings, placental weight, type of
      delivery, or type of ACLA. Twenty-seven ACLA-positive women were receiving
      prednisone. Chi square analysis showed the ACLA-positive mothers to have more
      spontaneous abortions (p = 0.02) and to have more children with congenital heart
      disease (5 ventricular septal defects and 2 atrial septal defects) (p = 0.006).
      In summary, infants born with congenital heart defects in women positive for ACLA
      did not have significant placental pathologic conditions when compared with
      control infants.

PMID- 8866296
TI  - Factors influencing acquired upper airway obstruction in newborn infants
      receiving assisted ventilation because of respiratory failure: an overview.
AB  - A critical review of published English literature was undertaken to identify the
      risk factors for the development of upper airway obstruction in the neonate after
      intubation for ventilatory support. An English-language computerized search
      (MEDLINE database from 1966 forward) was done to identify relevant studies; in
      addition, the reference list of retrieved articles was reviewed to ensure
      completeness of the search. Papers that presented original data on the risk
      factors for the development of postintubation upper airway obstruction were
      included. The inconsistency in defining the population being studied and the lack
      of a standard definition and method for reporting severity of subglottic stenosis
      make it difficult to interpret the risk factors associated with subglottic
      stenosis, and its incidence among various institutions cannot be compared.
      Prematurity was the only risk factor that was identified in the published
      literature that one could reliably and consistently associate with the
      development of subglottic stenosis.

PMID- 8866297
TI  - Perinatal stressors as predictors of symptoms of posttraumatic stress in mothers
      of infants at high risk.
AB  - We investigated the relationship between the stress of a high-risk birth and the
      development of symptoms of posttraumatic stress disorder in mothers. Six measures
      of perinatal stressors (gestational age of the baby, birth weight, length of
      hospital stay for the baby, a postnatal complications rating for the infant, and
      Apgar scores at 1 and 5 minutes) were used to predict the frequency of
      posttraumatic stress symptoms. Severity of infant complications, gestational age,
      and length of stay accounted for 35% of the variance in reports of posttraumatic
      stress symptoms. Both mothers of premature infants and mothers of term infants
      hospitalized in a neonatal intensive care unit reported significantly more
      symptoms of posttraumatic stress than mothers of healthy term infants (p < 0.01).
      We conclude that the birth of an infant at high risk, especially one with severe
      medical complications, can have long-term emotional consequences for the baby's
      mother.

PMID- 8866298
TI  - Pentoxifylline does not delay bacterially induced preterm delivery in rabbits.
AB  - OBJECTIVE: Our purpose was to determine whether pentoxifylline, a potent cytokine
      inhibitor, would delay bacterially induced preterm delivery in rabbits. STUDY
      DESIGN: The study was a randomized, blinded, prospective trial. Twenty-seven
      rabbits underwent laparotomy. Of these, five (shams) received an intrauterine
      injection of endotoxin-free water, and the remaining 22 received an injection of
      10(5) Escherichia coli into the lower uterine segment. Postoperatively the
      animals that received the Escherichia coli were divided into two groups. The
      placebo group (n = 11) received subcutaneous injections of saline solution three
      times a day and the treatment group (n = 11) received pentoxifylline 20 mg/kg/day
      in three divided doses. The following parameters were evaluated: (1) time until
      delivery, (2) time until death, and (3) intrauterine pathologic features.
      RESULTS: All five of the sham rabbits were delivered at term without any evidence
      of infection. There were no differences in the preterm delivery rates between the
      placebo group (eight of 11) and the pentoxifylline-treated group (seven to 11).
      However, there was a trend toward prolonging time until death in the treatment
      group. There were no differences in intrauterine pathologic feature between the
      placebo and treatment groups. CONCLUSION: Pentoxifylline does not delay
      Escherichia coli induced preterm delivery in rabbits.

PMID- 8866299
TI  - Prenatally diagnosed ureterocele presenting as fetal bladder outlet obstruction.
AB  - The prenatal detection of fetal genitourinary abnormalities is becoming more
      frequent. The exact nature of these anomalies is frequently difficult to
      delineate before delivery. We report a case of fetal bladder outlet obstruction
      caused by an ectopic ureterocele associated with a duplicated renal collecting
      system, which was visible on prenatal ultrasonographic examination. Postnatal
      follow-up is presented.

PMID- 8866300
TI  - Transient neonatal diabetes mellitus and macroglossia.
AB  - Transient neonatal diabetes mellitus is an uncommon disorder. Macroglossia in
      association with transient neonatal diabetes mellitus has been reported only
      twice before. We report the case of a 21-day-old male infant referred from a
      peripheral hospital for management of hyperglycemia. The mother was a 21-year-old
      primigravid in good health. There was no history of diabetes or drug or alcohol
      exposure. The pregnancy was complicated by intrauterine growth retardation and
      oligohydramnios from 30 weeks' gestation and the birth weight at 38 weeks'
      gestation was only 1480 gm. Physical examination revealed dysmorphic features and
      asymmetric growth retardation. The admission weight (1840 gm) and length (40.5
      cm) were 5 SDs less than the mean and head circumference (32.5 cm) was 1 SD less
      than the mean. Dysmorphic features included macroglossia, large fontanelles,
      hypospadias, umbilical hernia, and bilateral inguinal hernias. Hyperglycemia had
      been noted on day 1 of life with an initial blood glucose value of 16 mmol/L (288
      mg/dl). Despite treatment with regular insulin blood glucose control continued to
      be erratic. Therefore a regimen of daily NPH insulin was begun, which has a
      smoother action. Interestingly, from day 41 to day 47 the infant did not receive
      insulin and a crude control of the blood glucose was demonstrated. Peak levels of
      blood glucose in excess of 20 mmol/L (360 mg/dl) were followed by drops to levels
      less than 2 mmol/L (36 mg/dl) without insulin administration. This abnormal
      pattern of glucose control may represent poorly regulated release of endogenous
      insulin. However, because of unsatisfactory glucose levels administration of
      daily NPH insulin was reintroduced. The infant was discharged from the hospital
      on day 50 and administration of insulin was discontinued uneventfully at 9
      months. At 1 year the hemoglobin A1c level was still normal and the infant's
      weight was at the 10th percentile. Macroglossia was less pronounced. Development
      showed mild delay in gross motor milestones.

PMID- 8866301
TI  - Personal computer teleradiology interhospital image transmission of neonatal
      radiographs to facilitate tertiary neonatology telephone consultation and patient
      transfer.
AB  - OBJECTIVE: Our purpose was to study the ability of personal computer
      teleradiology (PCT) to improve the quality of communication between physicians
      during newborn infant transfers and consultations. STUDY DESIGN: In the first
      part of the study 36 radiographs of neonatal intensive care unit patients were
      transmitted by PCT. The pediatrician reviewed the original films and three
      neonatologists reviewed the PCT images. Their interpretations were scored by use
      of criteria established by a neutral reader. In the second part chest x-ray films
      (CXR) of 31 newborns weighing > 2000 gm with respiratory distress were
      transmitted by PCT. A pediatrician and three neonatologists participated in an
      exercise to simulate a telephone neonatology consultation. Patient severity
      assessments as measured by assignments to receive intermediate or intensive care
      were compared before and after neonatologists viewed the PCT image of the CXR.
      RESULTS: In part 1 of the study neonatologists correctly identified 98%, 91%, and
      98% of the x-ray interpretation scoring items, whereas at best the pediatrician
      identified 82% of the scoring items (p = 0.002). In part 2 neonatologists
      correctly assigned patient care levels an average of 73% after reviewing a
      standard clinical profile and a written description of the infant's CXR. After
      reviewing a PCT image of the infant's CXR, patient care level assignments were
      correctly assigned an average of 67%. The interpretation of the PCT CXR image was
      consistent with the radiologic report of record in 90 of 93 interpretations (31
      cases read by three neonatologists). CONCLUSIONS: PCT represents an inexpensive
      means to accurately send a radiographic image over the phone as part of a
      telephone consultation. Neonatologists were able to interpret teleradiology
      images more accurately than a pediatrician reviewing the original film. Although
      this did not result in an improvement in the neonatologists' ability to determine
      patient severity on the basis of the model used in part 2, their identification
      of serious radiographic findings missed by the pediatrician can only suggest that
      teleradiology may be beneficial in certain instances. Although verbal
      communication can often suffice in a telephone consultation or transfer, there
      may be specific instances when visualizing a radiographic image such as an x-ray
      film or computed tomographic scan can provide important information that cannot
      be optimally described verbally. Rural hospitals can form interhospital image
      transmission links with tertiary center resources.

PMID- 8866302
TI  - The messenger case.
AB  - Increasingly, parents are asking for the right to make resuscitation and
      treatment decisions for their newborn infants at high risk for mortality and
      morbidity. Failure of neonatologists to honor such parental wishes has led to
      criticism in the media and public disenchantment with neonatology. These issues
      were dramatized in a recent trial in which a father was charged with manslaughter
      after he removed his extremely premature son from life support to stop treatment
      administered against the family's wishes. Guidelines giving parents greater
      latitude in treatment decisions would help avoid similar tragic situations and
      would help restore public confidence in neonatology.

PMID- 8866303
TI  - Fetal ovarian torsion appearing as a solid abdominal mass.
AB  - Fetal and neonatal ovarian cysts can be small asymptomatic lucencies or large
      symptomatic echocomplex masses that can cause intestinal obstruction and
      peritonitis. Solid masses are the most rare form of ovarian cysts. A fetus,
      anatomically unremarkable at 16 weeks' development, was found at 35 weeks to have
      a 5 x 5 cm solid mass. After delivery a laparotomy was performed, and a torsed
      ovary measuring 8 x 7 cm was removed. The infant did well after the procedure.
      Over 400 cases of perinatal ovarian cysts have been reported in the literature.
      Only 1% of these are purely echodense. When a fetal abdominal mass is present,
      separate from bowels and kidneys, a torsed ovary should be considered in the
      differential diagnosis. Management of the pregnancy and infant may be guided by
      the fetus or neonate's symptoms.

PMID- 8866304
TI  - Abdominal lymphangioma in a preterm infant.
AB  - A newborn infant, noted on prenatal ultrasonography to have a huge, multiseptated
      cystic intraabdominal mass, had severe respiratory failure at birth because of a
      massively distended abdomen. Acute treatment included removal of 1.7 L of serous
      fluid, aggressive respiratory support, and numerous diagnostic studies.
      Definitive therapy was excision of the cyst by laparoscopy. Pathologic
      examination showed cystic lymphangioma.

PMID- 8866305
TI  - Ventilatory management casebook. Gastric perforation probably caused by
      glucocorticoid administration.

PMID- 8866306
TI  - Neonatal radiology casebook. Splenic hematoma as a cause of hypovolemic shock in
      a very low birth weight neonate.

PMID- 8866307
TI  - Special imaging casebook. Extralobar sequestration with type II cystic
      adenomatoid malformation.

PMID- 8866308
TI  - Manslaughter or a legitimate parental decision? The Messenger case.

PMID- 8866309
TI  - Manslaughter or a legitimate parental decision? The Messenger case.

PMID- 8866310
TI  - Aspartate aminotransferase (AST) levels in human periodontium-derived cells.
AB  - The ability to objectively assess periodontal disease activity can significantly
      affect periodontal therapy. Aspartate aminotransferase (AST) is released
      extracellularly upon tissue destruction which suggests its potential as a key
      index in a quantitative assay for evaluating periodontal disease activity. The
      purpose of the present research was to assess the origin of AST in gingival
      crevicular fluid (GCF) in vitro. An experimental kit was used for the measurement
      of AST level in human gingival epithelial cells (HGEs), human gingival
      fibroblasts (HGFs), human periodontal ligament fibroblasts (HPLFs),
      polymorphonuclear leukocytes (PMNs), and plasma in peripheral blood. AST activity
      levels were observed in all of the periodontally derived cells, PMNs, and plasma.
      A significantly high level of AST activity was observed in HGEs (104.93 +/- 8.13
      KU/1000 cells). The level of AST activity in HPLFs was 18.09 +/- 3.73 KU/1000
      cells. AST activity in PMNs was significantly low, approximately 2% of that
      observed in HPLFs. These findings may suggest that AST level in GCF is correlated
      with the destruction of periodontal tissue.

PMID- 8866311
TI  - Comparison of 2 desensitizing dentifrices with a commercially available fluoride
      dentifrice in alleviating cervical dentine sensitivity.
AB  - Previous studies have demonstrated efficacy of desensitizing dentifrices
      containing strontium acetate/sodium fluoride (SrAc2F) and potassium
      chloride/sodium monofluorophosphate (KCl/MFP) in alleviating discomfort arising
      from cervical dentine sensitivity (CDS). The aim of this investigation,
      therefore, was to determine efficacy of a SrAc2F dentifrice compared with KCl/MFP
      and a commercially available fluoride dentifrice containing sodium
      fluoride/sodium monofluorophosphate (NaMFP). Fifty-six patients participated in a
      2-center double-blind, 3-way comparative parallel 6-week clinical study. Patients
      were evaluated at 0, 2, and 6 weeks for tactile (Yeaple probe), air sensitivity
      (dental air syringe), and subjective perception of pain (VAS scores). Results for
      Yeaple probe scores (Wilcoxon tests) between 2 weeks and baseline were highly
      significant for KCl/MFP, significant for NaMFP and nonsignificant for SrAc2F;
      scores between 6 weeks and baseline were, however, highly significant for all
      groups. Subjective Yeaple probe VAS scores (paired t-tests) between 6 weeks and
      baseline were significant for all groups; significance was demonstrated in the
      KCl/MFP group between 2 weeks and baseline. Subjective air visual analogue scores
      (paired t-tests) between 2 weeks and baseline were highly significant for all
      groups. There were no significant differences between groups at any time point.
      The results of the study demonstrated that the commercially available fluoride
      containing dentifrice was as effective as the 2 desensitizing dentifrices in
      alleviating CDS over time.

PMID- 8866312
TI  - Plasminogen activator activity is decreased in rat gingiva during diabetes.
AB  - Diabetes produces extensive alterations of collagen metabolism including enhanced
      gingival collagenase activity. However, the mechanism for this enhanced enzyme
      activity is unclear. Collagenase is secreted from cells in a latent form and
      plasmin has been proposed as an important in vivo activator of procollagenase.
      Plasmin is converted from its precursor, plasminogen, by the proteolytic action
      of a serine proteinase, plasminogen activator (PA). The current study was
      therefore undertaken to determine the effect of diabetes on gingival PA activity
      in the rat. Since doxycycline is a potent collagenase inhibitor, the effect of
      doxycycline on gingival PA activity was also investigated. Eighteen male, Sprague
      Dawley rats were made diabetic by streptozotocin injection (7 mg/100 g). Control
      rats (N = 8) were sham-treated. Doxycycline (5 mg/day/rat) was administered to 9
      of the 18 diabetic rats by gavage on a daily basis. The other 9 diabetic rats
      were administered with saline. After 3 weeks, blood and gingival tissue were
      collected from each rat for the determination of glucose level and gingival PA
      activity. The tissues were then minced and extracted with 5 mM sodium phosphate
      containing 1% Triton X-100. PA assay was performed using chromatogenic substrate
      to determine PA activity in the extracts. Gingival PA activity in the diabetic
      rats was significantly reduced compared to the control (13.5 +/- 1.6 vs. 36.0 +/-
      3.3 microunits/100 micrograms protein, P < 0.01). Doxycycline administration to
      diabetic rats had no effect on the already reduced gingival PA activity (10.4 +/-
      3.5 in doxycycline-treated rats vs. 13.5 +/- 1.6 mu units/100 micrograms protein
      in untreated diabetic rats). PA activities in gingival tissues from the diabetic,
      nondiabetic control and doxycycline-treated diabetic groups were also
      demonstrated on zymographs as lytic bands. Regarding the well-known fact that
      gingival collagenase activity is enhanced during diabetes, our results did not
      support the notion that this biochemical alteration is attributed to increased
      activation of procollagenase by PA.

PMID- 8866313
TI  - Characterization of matrix metalloproteinase (MMP-8 and -9) activities in the
      saliva and in gingival crevicular fluid of children with Down's syndrome.
AB  - Previous studies have shown increased susceptibility to periodontal diseases in
      children with Down's syndrome (DS). The mechanisms involved in the periodontal
      inflammatory processes in DS are not fully understood. The present study
      characterized the periodontal status of 9 non-institutionalized DS children 9 to
      17 years old (mean 13.6 years) relative to their age-matched systemically and
      periodontally healthy controls. The periodontal status was assessed by visible
      plaque index (VPI), gingival bleeding index (GBI), and probing depth. We also
      assessed, by sodium dodecyl sulphate polyacrylamide gel electrophoresis/laser
      densitometry and by zymography, the collagenase and gelatinase activities in the
      gingival crevicular fluid (GCF) and saliva samples collected from DS patients and
      from the controls. Eight of the nine DS children showed a periodontium comparable
      to that seen in healthy controls; beginning alveolar bone loss was
      radiographically seen in the DS patient with deep periodontal pockets. The
      endogenously active collagenase and total collagenase activities were slightly
      higher in GCF of DS children compared to healthy controls. Western blot
      demonstrated that GCF collagenase of DS patients was human neutrophil collagenase
      (MMP-8 or collagenase-2), which occurred in 75 kDa proMMP-8 and in DS patients,
      but not in controls, also in 65 kDa active MMP-8 form and occasionally lower 40
      50 kDa MMP-8 species. Zymographic analysis revealed the presence of 120 kDa (MMP
      9 complexed with neutrophil gelatinase associated lipocalin or NGAL), 92 kDa (MMP
      9) and 72 kDa (MMP-2) gelatinases in DS and control GCF. Especially in DS GCF MMP
      9 occurred in part in 82-85 kDa activated form. Salivary collagenase in DS was
      high when compared to controls but of the same MMP-8 type as in control saliva.
      Our findings suggest that in vivo activated MMP-8 in GCF derived from triggered
      PMNs and/or cytokine-induced periodontal fibroblasts may reflect periodontal
      tissue and alveolar bone destruction seen in the early stages of
      gingivitis/periodontitis associated with Down's syndrome.

PMID- 8866314
TI  - Interleukin-1 beta, prostaglandin E2, and immunoglobulin G subclasses in gingival
      crevicular fluid in patients undergoing periodontal therapy.
AB  - Determination of the presence of inflammatory products found in gingival
      crevicular fluid (GCF) may be of value in evaluating both periodontal disease
      status and the outcome of therapy. Immunoglobulin G subclasses 1 through 4
      (IgGs), interleukin 1-beta (IL-1 beta), and prostaglandin E2 (PGE2) have all been
      shown to be present in GCF. This study monitored IgGs, IL-1 beta, and PGE2 in GCF
      of 18 adult patients as they progressed through periodontal treatment toward
      maintenance therapy. Sites were selected from the most severely affected sextant
      as determined by probeable crevice depth (PD) at initial examination (IE). GCF
      was collected on four occasions: initial examination; 4 weeks after completion of
      initial therapy (oral hygiene counseling, and scaling and root planing); 3 months
      after completion of surgery; and 7 to 9 months later at a maintenance visit. All
      variables were reduced to binary form (positive or negative), and break points
      chosen to separate the approximately symmetrical bell-shaped areas (negatives)
      from the skewed tails (positives). Repeated measures analyses of variance were
      performed to detect significant changes in all variables across time. Significant
      improvements were observed for all the clinical variables measured: PD,
      attachment level, and bleeding on probing. However, significant reductions for
      the GCF components only occurred in the concentrations of IL-1 beta and PGE2, but
      were not evident until the maintenance sampling. Surprisingly, GCF:serum ratios
      of IgG subclasses did not change significantly over the course of the
      investigation. The robustness of the levels of these components may be due to
      inflammation associated with the healing process, or to a further plaque induced
      response.

PMID- 8866315
TI  - Quantitative analysis of periodontal defects in a skull model by subtraction
      radiography using a digital imaging device.
AB  - This paper describes a quantitative study of periodontal defects produced in a
      skull model using subtraction images obtained with a digital imaging device,
      radiovisiography (RVG). Analysis using radiovisiography was compared to changes
      in weight and volume determined by physical measurements. Four types of
      periodontal defects were studied: 2-wall, 3-wall, crater, and furcation. All
      defects were fabricated on posterior teeth in alveolar bone and done with
      triplicate samples. Defects were made progressively larger in approximately 1 mm
      steps allowing examination of defects ranging from 1 mm to 5 mm. Radiographic
      images before and after each step were obtained with a radiovisiography system
      and subtracted. Changes in weight and defect volume were also recorded and
      compared to the results obtained after each step from the digital subtraction.
      For each defect type, a regression analysis was performed to compare changes in
      bone mass determined by weight with calculated bone loss determined by
      subtraction radiography or by volume measurements. When the calculated bone
      losses were compared to the true bone losses it was evident that the subtraction
      method frequently, but not always, underestimated the lesion sizes. For all
      lesions the average underestimation was 22%. The largest underestimation occurred
      with furcation lesions where the measured bone loss was underestimated on average
      by 67%. Two-walled lesions were underestimated by 30%, 3-wall lesions by 3%, and
      crater lesions were overestimated by 10%. Furthermore, the accuracy of each 1 mm
      step in bone loss varied considerably. At present, the imaging system is not
      sufficiently accurate to establish absolute determinations of the bone loss, but
      would be clinically useful in determining relative changes in bone loss or gain
      after treatment. In addition, caution must be taken in interpreting a given
      change in calculated bone loss, since considerable variation may result in either
      underestimation or overestimation of bone loss.

PMID- 8866316
TI  - A clinical evaluation of demineralized freeze-dried bone allograft in combination
      with tetracycline in the treatment of periodontal osseous defects.
AB  - The purpose was to evaluate the use of demineralized freeze-dried bone allograft
      reconstituted with 50 mg/ml tetracycline hydrochloride in the treatment of
      intrabony periodontal defects. Fifteen systemically healthy patients (12 females,
      3 males; aged 35 to 61) with moderate-advanced periodontitis were treated.
      Patients had 3 osseous defects with probing depths (PD) > 5 mm after initial
      therapy. Each site in each subject was randomly assigned to one of the following
      groups: 1) demineralized freeze-dried bone allograft reconstituted with 50 mg/ml
      tetracycline (DFDBA + TCN); 2) demineralized freeze-dried bone allograft alone
      (DFDBA); or 3) debridement only (D). Clinical measurements were taken the day of
      surgery, 6 months, and 1 year. Standardized radiographs were taken at baseline
      and 1 year and were evaluated by computer assisted densitometric image analysis
      (CADIA). Clinical measurements included gingival recession, PD, clinical
      attachment level, and mobility. Osseous defect measurements were taken at
      baseline and at the 1 year reentry. No adverse healing responses occurred. The
      results showed that all patients had a statistically significant improvement in
      probing depth and attachment level at 1 year. Osseous measurements showed bone
      fill of 2.27 mm (51.6%) for the DFDBA + TCN group, 2.20 mm (52.4%) for the DFDBA
      group, and 1.27 mm (32.8%) for the D group. Defect resolution was 77.3% for the
      DFDBA + TCN group, 77.9% for the DFDBA group, and 63.8% for the D group. The mean
      CADIA values were 5.04 for the DFDBA + TCN group, 6.79 for the DFDBA group and
      2.78 for the D group. The CADIA values did not correlate with the clinical
      parameters. Although the grafted groups showed greater bone fill and defect
      resolution, there was no statistically significant difference in any of the
      clinical parameters between the treatment groups. This study suggests that there
      is no significant benefit from reconstituting the allograft with 50 mg/ml of
      tetracycline hydrochloride.

PMID- 8866317
TI  - Osseointegrated implants in patients treated for generalized severe adult
      periodontitis. An interim report.
AB  - This study presents oral rehabilitation with osseointegrated implants in
      partially edentulous patients treated for generalized severe adult periodontitis.
      Five female patients aged between 31 and 44 received a total of 36 implants and
      were observed for 1 year after insertion of the superstructure. Three months
      before implantation, venous blood samples were taken from the patients and five
      periodontally healthy controls, and the serum examined with highly sensitive
      ELISA test kits for interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6).
      Clinical examination covered the plaque index (PI) and gingival index (GI) at
      teeth and implants plus probing depth (PD) and clinical attachment level (CAL) at
      the teeth. Microbiological evaluation of teeth and implants was performed by dark
      field analysis, and DNA analysis was performed in addition 1 year after insertion
      of the superstructure. Radiological controls of the teeth were carried out with
      standard single-tooth films in the 2 years preceding implantation and at
      baseline. Following implantation, further controls of the teeth and implants were
      undertaken immediately after insertion of the superstructure and 1 year
      thereafter. The immunological examination revealed that the IL-1 beta (0.22 +/-
      0.2 pg/ml) (means +/- SD) and IL-6 (2.27 +/- 2.8 pg/ml) level was slightly, but
      not significantly, higher in the patients than in the control group (IL-1 beta:
      0.06 +/- 0.06 pg/ml and IL-6: 0.64 +/- 0.2 pg/ml) (P > 0.05). The clinical
      results show that the GI at the teeth rose slightly from 0.0 to 0.2, and at the
      implants from 0.3 to 0.4. The PI rose slightly from 0.3 to 0.7 at the teeth and
      from 0.2 to 0.9 at the implants. Neither the GI nor the PI revealed any
      significant difference between teeth and implants. Clinical attachment loss at
      the teeth was minimal at 4.7 to 4.8 mm. Comparison between the teeth and the
      implants revealed no essential difference in bacterial flora; neither
      Actinobacillus actinomycetemcomitans nor Porphyromonas gingivalis was recorded at
      any location. Small quantities of Prevotella intermedia were detected at the
      teeth and implants of one patient. Radiological evaluation 1 year after insertion
      of the superstructure revealed a mean bone loss of 0.62 mm at the implants. The
      bone loss at the teeth during the same period was 0.3%, whereas it had been 1.5%
      in each of the 2 previous years. These results suggest that there is only a
      slight difference between the periodontal and peri-implant areas in patients with
      generalized severe adult periodontitis. The full potential for implants in these
      patients, however, needs to be shown in controlled longitudinal studies.

PMID- 8866318
TI  - Levels of cytokines and collagen type I and type III as a function of age in
      human gingivitis.
AB  - The objective of this study was to examine the age-dependent relationships
      between levels of inflammatory cytokines and collagen in human gingival
      inflammation. The gingival biopsies were obtained from 142 patients, divided into
      the following age groups: 6 to 14 years (prepubertal children); 18 to 35 years
      (young adults); 36 to 54 years (mature adults); and 55 years or above. The
      patients were also divided according to the severity of gingivitis. The tissues
      were analyzed for the contents of the inflammatory cytokines interleukin (IL)-1
      beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) using specific
      ELISA kits, and interstitial collagen type I and type III using the ELISA method
      and specific antibodies. We found that in young adults, levels of IL-1 beta and
      IL-6 were significantly higher in inflamed than in non-inflamed gingiva. Total
      collagen in the young adults, however, was lower in inflamed than in non-inflamed
      gingiva. There was no significant difference in the levels of either IL-8 or TNF
      alpha between inflamed and non-inflamed gingiva independent of age. No difference
      in the level of collagen type I between the inflamed and non-inflamed gingiva was
      found in any age groups. The level of collagen type III was lower in inflamed
      than in non-inflamed gingiva in both children and > or = 55 year group. The
      results indicate a disparity in the effect of age on the levels of cytokines and
      of collagen type I and type III in both clinically normal and inflamed gingiva.

PMID- 8866319
TI  - Short-term responses to periodontal therapy in insulin-dependent diabetic
      patients.
AB  - This investigation studied relative changes in periodontal conditions of 18
      insulin-dependent diabetic patients. Measures of gingival inflammation,
      crevicular fluid aspartate aminotransferase (AST) levels, probing depth and
      attachment levels, the presence of three periodontal pathogens (Porphyromonas
      gingivalis, Bacteroides forsythus, and Actinobacillus actinomycetemcomitans) and
      serum antibody titers to these bacteria, and blood sugar levels (glycosylated
      hemoglobin, HbAlc) were studied before and 2 months after non-surgical
      debridement. Antibody titers to the same bacteria were also studied in sera from
      18 sex- and age-matched periodontally healthy and non-diabetic subjects.
      Periodontal conditions showed significant improvement. The mean probing depth at
      4 of the worst sites selected in each patient decreased from 5.7 mm to 4.8 mm (p
      < 0.0001). The mean full width probing depth changed from 2.9 mm (s.d. +/- 0.2)
      to 2.5 mm (s.d. +/- 0.3). A mean gain of 0.4 mm attachment level was recorded (P
      < 0.0001). The mean AST value decreased from 1009 microIU to 518 microIU (P <
      0.006). Minimal differences in mean glycosylated hemoglobin values (HbAlc) were
      noticed before and after treatment. A. actinomycetemcomitans was never detected.
      P. gingivalis was present at 7% of the sites both before and after treatment. B.
      forsythus was found at 29% of sites (50% of patients) before and at 36% of sites
      (61% of patients) after treatment. Positive associations were found between the
      presence of B. forsythus and AST values, gingival index, probing depth, and
      attachment level (P < 0.05). Baseline serum IgG titers to P. gingivalis were
      significantly lower in the patients with diabetes (9.5 ELISA units vs. 28.5 ELISA
      units in the healthy controls). IgG titers to B. forsythus did not differ between
      diabetic and non-diabetic subjects. No changes in IgG titers occurred after
      treatment. Clinical improvements after mechanical non-surgical therapy in
      patients with insulin-dependent diabetes mellitus were modest after 2 months.
      Treatment did not eliminate B. forsythus and P. gingivalis and did not affect IgG
      titer responses. More intense therapy, and longer follow-up times, may be
      necessary to see more pronounced clinical and systemic effects.

PMID- 8866320
TI  - Clinical evaluation of demineralized-unicortical-ilium-strips for guided tissue
      regeneration.
AB  - This study compared demineralized-unicortical-ilium-strips (DUIS) and an expanded
      polytetrafluoroethylene (ePTFE) physical barrier in combination with decalcified
      freeze-dried bone allograft (DFDBA) for treatment of Class II mandibular
      furcations. Twenty patients with adult periodontitis and at least 2 furcation
      invasions participated in this study. Probing depth (PD), clinical attachment
      level (CAL), and bone fill were measured at 6 and 12 months. Standardized
      radiographs were analyzed using computer assisted densitometric image analysis
      (CADIA). Fifteen of 20 patients completed the 12-month evaluation. At 6 months
      both control and test groups showed significant reductions in PD from baseline (P
      < 0.01). PD reduction for the ePTFE + DFDBA sites was 2.13 mm +/- 1.25, and the
      DUIS + DFDBA, 1.77 mm +/- 1.21. CAL at 6 months was sustained to 12 months when
      the net gains in CAL for ePTFE + DFDBA being 1.30 mm +/- 1.45 (P < 0.01) and for
      DUIS + DFDBA sites 1.13 mm +/- 1.68 (P < 0.02). The horizontal furcation PD
      decreased 2.87 mm +/- 1.68 (P < 0.01) in the ePTFE + DFDBA and 1.70 mm +/- 1.69
      (P < 0.01) for DUIS + DFDBA sites over 12 months. The evaluation of the hard
      tissue response at the 12-month re-entry demonstrated a bone fill of 2.37 mm
      (75%) +/- 2.04 (P < 0.01) with ePTFE + DFDBA and 1.83 mm (79%) +/- 1.57 (P <
      0.01) with DUIS + DFDBA. DUIS material and ePTFE showed significant improvements
      in clinical parameters and neither material proved to be significantly better.
      However, a larger sample size may have permitted us to demonstrate statistically
      significant differences between the materials. The positive results from the
      utilization of DUIS for GTR and the advantage of its bioresorbability warrant
      further investigation. The study found limitations in the use of CADIA for
      evaluation of guided tissue regeneration in furcations.

PMID- 8866322
TI  - Histologic evaluation of human extraction sockets treated with demineralized
      freeze-dried bone allograft (DFDBA) and cell occlusive membrane.
AB  - This study evaluated new bone formation in human extraction sockets treated with
      demineralized freeze-dried bone allografts (DFDBA) and celloc occlusive
      membranes. Hard tissue biopsies of 7 sites in 6 patients were obtained 14 weeks
      to 13 months following extraction and grafting. Histologic analysis revealed that
      individual particles of DFDBA were discernible up to 13 months in situ. In all
      samples, all particles of DFDBA were well incorporated within new bone, which
      exhibited osteocyte-containing lacunae. Distinct cement lines clearly demarcated
      the DFDBA particles from the surrounding, intimately-apposed woven and lamellar
      bone. The marrow demonstrated a mild degree of fibrosis without signs of
      inflammatory reaction. There was also a notable lack of fibrous encapsulation of
      the allograft, and little osteoclasis was observed. Our findings demonstrate that
      commercially available DFDBA has the potential to function physically as a nidus
      for appositional new bone growth in alveolar sockets following tooth extraction.
      Further investigations of the biological activity of DFDBA in situ are warranted.

PMID- 8866321
TI  - Periodontal management of Glanzmann's thrombasthenia: report of 3 cases.
AB  - Glanzmann's thrombasthenia was reported and described as a bleeding diathesis
      seen in children and characterized by diminished clot retraction. It is an
      autosomal recessive bleeding disorder. The disease is marked by frequent
      mucocutaneous hemorrhages either due to defective function of the platelets or
      lack of fibrinogen binding membrane receptor glycoproteins IIb/IIIa which are
      located on the surface of the platelets. Case reports on 3 siblings, a girl of
      11, and 2 boys of 12 and 16 years old with Glanzmann's thrombasthenia are
      reviewed. The major complaint of the patients was gingival bleeding. Periodontal
      treatment was performed under platelet transfusion and proper oral hygiene
      instruction was given. The patients were followed for 6 months and no periodontal
      complications developed during this time. Proper periodontal care for such
      patients is essential both for local and systemic health.

PMID- 8866323
TI  - Lasers in periodontics.
AB  - Publicity about the use of lasers in dentistry has generated considerable
      interest in both professional and lay audiences. The purpose of this report is to
      provide information for members of the dental profession about the current and
      potential application of laser technology to periodontal practice.

PMID- 8866324
TI  - Systemic antibiotics in periodontics.
AB  - This position paper addresses the role of systemic antibiotics in the treatment
      of periodontal disease. The document consists of three sections: 1) concept of
      antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy;
      and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn
      in this paper represent the position of The American Academy of Periodontology
      and are intended for the information of the dental profession.

PMID- 8866325
TI  - Physicochemical properties of calcium polycarbophil, a water-absorbing polymer.
AB  - The physicochemical properties of calcium polycarbophil were examined. Calcium
      polycarbophil was decalcified rapidly under acidic conditions, affording
      polycarbophil. Polycarbophil absorbed about 10 times its own weight of water
      under acidic conditions, but the swelling ratio markedly increased at above pH
      4.0 and reached 70 times the initial weight under neutral conditions. The
      swelling of polycarbophil was not affected by non-ionic osmolarity, but was
      affected by ionic strength, showing a decrease with increase of ionic strength.
      Monovalent metal ions such as sodium and potassium ions in gastrointestinal fluid
      did not reduce the equilibrium swelling of polycarbophil, but divalent ions such
      as calcium and magnesium ions did. However, calcium ion only slightly reduced the
      equilibrium swelling under sodium-rich conditions. The viscosity (as an indicator
      of fluidity) of polycarbophil was larger than that of CMC-Na at every shear rate
      and polymer content examined.

PMID- 8866326
TI  - Biodegradable injectable implant systems for long term drug delivery using poly
      (lactic-co-glycolic) acid copolymers.
AB  - Poly (lactide-co-glycolide) (PLG), is one of the most widely employed
      biodegradable synthetic polymers for sustained-release preparations. In the
      present work, PLG (50:50) copolymer has been used to deliver diclofenac sodium in
      the form of microspheres and in situ gel-forming systems, both of which can be
      injected subcutaneously. The pharmacodynamic and pharmacokinetic studies in the
      adjuvant-induced arthritic rats showed that the microspheres offered steady
      therapeutic levels of the drug in the plasma for about 16 days following a single
      subcutaneous injection. However, the in situ gel-forming system provided a
      significantly higher maximum plasma concentration and increased inhibition of
      inflammation, maintained for about 10 days. Injectable microspheres and in situ
      gel-forming implant systems of PLG (50:50) copolymer may therefore be considered
      as prospective implantable controlled-release dosage forms to deliver drugs in
      long-term therapy of chronic ailments.

PMID- 8866327
TI  - Influence of pH on skin permeation of amino acids.
AB  - Skin permeation of amino acids through excised rat skin was measured at various
      pH values. The permeabilities varied with the donor pH and amino acid, indicating
      that each ionic species of amino acid may have a different permeability. The
      permeability coefficient of each ion was estimated from the permeability-pH
      profiles using the dissociation constants. The estimated values for mono-cation
      and uncharged zwitterion were not dependent on the lipophilicity but on the size
      of the amino acid, suggesting a porous mechanism of transport. The permeability
      coefficient was highest for di-cation, followed by mono-cation, positively
      charged, uncharged and negatively charged zwitterions. The electrical potential
      difference across the skin was too small to affect the permeation of ions. The
      permselective property of skin thus seems to be determined by the difference of
      diffusivity in aqueous pores of skin due to the hydration of ions and other
      factors.

PMID- 8866328
TI  - Characteristics of shed snake skin permeability to indomethacin and fatty
      alcohols.
AB  - To investigate the utilities of a shed snake skin as a model membrane for
      preclinical studies of transdermal drug delivery, the flux of indomethacin was
      determined under various conditions by using a diffusion cell. The flux of fatty
      alcohols was determined and compared with that in human skin reported in
      references. The esterase activity of shed snake skin was also determined. It was
      found that the flux of indomethacin decreased with an increase of pH and the
      amount of ethanol in a vehicle. The flux of indomethacin increased by the
      addition of Azone, N-methyl-2-pyrrolidone and N,N-dimethyl-m-toluamide in the
      cream. The flux of fatty alcohols in shed snake skin was greater than that
      reported in human skin, and shed snake skin had similar esterase activity to
      human skin.

PMID- 8866330
TI  - Development and validation of a pig model for colon-specific drug delivery.
AB  - The purpose of this investigation was to develop a pig model for colonic drug
      delivery and to validate the model by determining whether the physiology of the
      pig colon had been significantly altered after the surgical implantation of a gut
      cannula into the terminal ileum of the pig. A fistula was created in the terminal
      ileum of the pig, and a cannula fitted for the purpose of directly administering
      drug formulations to a point just anterior to the ileocaeco-colonic valve of the
      gastrointestinal tract. The cephalic vein of the pig was also cannulated to
      enable continued blood sampling. Sulphasalazine was used as the model drug for
      the validation study. In the intact colon, sulphasalazine is metabolized by the
      gut microflora to sulphapyridine which is then absorbed. Sulphasalazine was
      administered orally to non-fistulated and fistulated pigs and then ileally, via
      the gut cannula, to fistulated pigs. Absorption of sulphapyridine was monitored
      by HPLC analysis of plasma samples. There was no significant difference in the
      absorption obtained for the three groups. Thus it is demonstrated that the colon
      physiology had not been altered. The colonic pig model is ideal for studying
      factors affecting the colonic absorption of drugs and as a means for developing
      drug delivery systems with improved absorption properties.

PMID- 8866331
TI  - Immunological detection of type II collagen degradation: use in the evaluation of
      anti-arthritic therapies.
AB  - Propagated Swaram rat chondrosarcoma cells, rabbit chrondrocytes (from articular
      cartilage of knee, shoulder and hip joints), and bovine nasal cartilage explant
      cultures were studied. Type II collagen (CII) and its peptide fragments were
      quantitated in cell medium and cell layer separately, using two previously
      developed assays; one assay employed a monoclonal antibody, C4F6, that reacts
      specifically with triple helical CII and the other assay used an antibody, EIE5,
      that reacts specifically with a peptide of CII. A time-dependent increase in the
      content of CII and CII-derived peptides was observed in both rat and rabbit
      cultures. In both culture systems the majority of the native type II collagen is
      found associated with the cell layer (97% in rat cultures and 73% in rabbit
      cultures), while the major part of the CII peptides is found in the media (73% in
      rat cultures, 88% in the rabbit cultures). The concentration of peptides in the
      media reaches approximately 2 micrograms mL-1 in both chondrocyte monolayer
      cultures after 4 days. The CII peptide assay employing E1E5 was well suited to
      quantitate articular cartilage collagen degradation in explant culture. thus it
      can be used to evaluate potential therapeutic agents that can modify or inhibit
      cartilage degradation. The assay has the added potential that it could be used in
      vivo to evaluate the effectiveness of potential metalloproteinase inhibitors in
      animal models of osteoarthritis or in clinical trials.

PMID- 8866329
TI  - Antitumour activity of mitoxantrone-loaded chitosan microspheres against Ehrlich
      ascites carcinoma.
AB  - Glutaraldehyde cross-linked chitosan microspheres containing the antineoplastic
      agent mitoxantrone were prepared and the antitumour activity was evaluated
      against Ehrlich ascites carcinoma in mice by intraperitoneal injections. The
      tumour inhibitory effect was followed by monitoring animal survival time and
      change in body weight for a period of 60 days. While the mean survival time of
      animals which received 2 mg and 1 mg of free mitoxantrone intraperitoneally was
      2.1 and 4.6 days, respectively, animals which received 2 mg mitoxantrone via
      microspheres showed a mean survival time of 50 days. Five out of 8 animals
      treated using microspheres lived beyond 60 days. The percentage ratio mean
      survival time of the treated group divided by the mean survival time of the
      untreated group for animals treated using mitoxantrone-loaded chitosan
      microspheres containing 2 mg of the drug was 290 compared with 12.2 for those
      which received 2 mg of the free drug. The antitumour effect of mitoxantrone
      loaded microspheres against Ehrlich ascites carcinoma was much higher than that
      of doxorubicin-loaded microspheres reported by previous workers. Our data
      demonstrate the potential of mitoxantrone-loaded chitosan microspheres for
      sustained drug delivery to minimize drug toxicity and maximize therapeutic
      efficacy.

PMID- 8866332
TI  - Preoperative lymph-node staining with liposomes containing patent blue violet. A
      clinical case report.
AB  - A case study is reported using patent blue violet entrapped in liposomes to
      localize lymph nodes before surgery. Liposomes containing 44 mg patent blue
      violet were injected into foot lymphatics of a patient due to undergo
      retroperitoneal staging-lymphonodectomy. Lymph nodes were readily visualized and
      removed, and urine and serum was collected for assay of the dye. The maximum
      concentration of patent blue violet in serum was 2.7 micrograms mL-1, 1.5 h after
      the termination of the injection, almost no dye was detectable by the time of the
      operation 24 h later. In the first urine sample (2 h after the termination of the
      injection) the concentration of patent blue violet was 1.3 micrograms mL-1, and
      subsequently diminished, with the last urine sample to contain detectable dye
      being collected 20 h later. A total of 0.8 mg dye (2% of the injected amount) was
      excreted in the urine suggesting 10% of the circulating amount of dye was renally
      excreted. Endolymphatic injection of patent blue violet simplifies the often
      difficult process of finding the lymph nodes and additionally reduces side
      effects. All surgery cases demanding a radical lymphonodectomy may profit,
      including testicular or bladder cancers and many gynaecological tumours.

PMID- 8866333
TI  - Suppression of adjuvant arthritis in rats by oral administration of type II
      collagen in combination with type I interferon.
AB  - The oral administration of 3 micrograms but not 300 micrograms of type II
      collagen (CII) significantly suppressed adjuvant arthritis in rats that was
      induced by immunization with Mycobacterium tuberculosis. Feeding 5000 units of
      type I interferon was also effective in downregulating the disease. More
      suppression of adjuvant arthritis was observed when both CII and interferon were
      orally given. Delayed-type hypersensitivity responses to M. tuberculosis were
      inhibited in interferon- but not in CII-fed animals. There were no delayed
      responses to CII in M. tuberculosis-immunized rats fed either CII or interferon.
      However, the delayed response to M. tuberculosis plus CII was significantly
      reduced by CII as well as interferon given orally. Feeding both CII and
      interferon was more effective in suppressing the delayed responses to M.
      tuberculosis plus CII. A similar suppression was observed in proliferative
      responses of lymph-node cells to M. tuberculosis, CII, or M. tuberculosis plus
      CII in-vitro. These results suggest that the suppression of adjuvant arthritis by
      oral administration of CII is due to tolerance to CII in which a bystander
      suppression mechanism appears to be involved. Orally administered interferon
      seems to suppress nonspecifically cellular immune responses. The oral
      administration of CII in combination with interferon may be a novel way to treat
      T cell-mediated diseases.

PMID- 8866334
TI  - Synergistic inhibition of human polymorphonuclear function by prostaglandin E1
      and linsidomine.
AB  - Polymorphonuclear cells (PMN) are the dominating inflammatory cell population in
      acute tissue injury and contribute to host-defence mechanisms by formation and
      release of chemical mediators. The aim of the present study was to investigate
      whether chemoattractant-induced PMN stimulation can be synergistically
      antagonized by vasodilatory prostaglandins and nitric oxide (NO), both being
      formed by the vasculature in inflamed areas. PGE1 (10 nM-10 microM) inhibited
      concentration-dependently formyl-methionyl-leucyl-phenylalanine (fMLP)-induced
      beta-glucuronidase and oxygen radical (O2.) release from human PMN. The NO donor
      linsidomine (100 microM) was ineffective, but significantly enhanced PGE1 effects
      on oxygen radical generation and enzyme release. The non-selective
      phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) (0.5 mM)
      potentiated PGE1 effects on all parameters measured. The combination linsidomine
      (100 microM) plus IBMX (0.5 mM) did not additionally reduce beta-glucuronidase
      release, but abolished fMLP-stimulated O2. generation. There was a stimulation of
      cAMP formation by PGE1 but not by linsidomine, both in the absence and presence
      of IBMX. It is concluded that the effects of linsidomine on PMN function and its
      synergism with PGE1 are not tightly correlated with total cAMP accumulation.
      Alternatively, the inhibition of O2. generation by linsidomine may be related to
      its ability to modulate the activation of the NADPH oxidase system or to scavenge
      free oxygen radicals.

PMID- 8866335
TI  - Rat protein binding and cerebral phospholipid affinity of the H3-receptor
      antagonist thioperamide.
AB  - The binding of thioperamide, a known H3-receptor antagonist, to rat plasma and
      proteins and its affinity for rat cerebral phospholipids are investigated.
      Thioperamide is strongly bound to plasma proteins (95-80% at plasma
      concentrations of 3.5-400 micrograms mL-1), and its binding can be resolved into
      two components a high-affinity, saturable component and a non-specific component.
      The drug has a high affinity for cerebral phospholipids, with a partition
      coefficient of approximately 100 (log K = 2.06 +/- 0.14), which should promote
      brain penetration and accumulation. Protein binding and cerebral phospholipid
      affinity can suggest the explanation of some differences reported in the
      literature on thioperamide distribution data: at low plasma concentrations of the
      drug, its protein binding (95% at 3.5 micrograms mL-1) can prevent brain
      accumulation, while at higher concentrations the free plasma fraction suddenly
      increases (> 10% at 18 micrograms mL-1) and it allows passive distribution to
      lipophilic tissues such as brain tissue.

PMID- 8866336
TI  - Kinetic studies of N-allenic analogues of tryptamine as monoamine oxidase
      inhibitors.
AB  - A series of N-allenic analogues of tryptamine in which the side chain is located
      at the 2 position of the indole ring, but which differed in the ring and side
      chain nitrogen substituents, were assayed kinetically as MAO A and MAO B
      inhibitors. All the compounds studied were mechanism-based inhibitors. The
      kinetic constants of each inhibition step Ki and ki, were determined for both MAO
      A and B. The data obtained indicated that these allenic derivatives show a
      greater selectivity and potency towards MAO A as inhibitors than the
      corresponding acetylenic derivatives.

PMID- 8866337
TI  - Mefloquine effect on disposition of halofantrine in the isolated perfused rat
      liver.
AB  - Halofantrine and mefloquine are antimalarial drugs used in the treatment of
      malaria, including that caused by chloroquine-resistant Plasmodium falciparum.
      Reports of drug-associated adverse reactions, including sudden death in one
      patient, have prompted concerns over the safety of halofantrine and the potential
      for drug-drug interactions. We used the isolated perfused rat liver (IPRL) model
      to investigate a possible hepatic metabolic or pharmacokinetic drug-drug
      interaction between halofantrine and mefloquine. Pharmacokinetic parameter
      estimates for halofantrine in the IPRL reflected the pattern seen in in-vivo
      studies with doses comparable with clinical doses. Halofantrine parameter
      estimates (mean +/- s.d.) were: volume of distribution (Vd), 7.53 +/- 1.45 mL (g
      liver)-1; clearance (CL), 0.11 +/- 0.07 mL min-1 (g liver)-1; initial
      distribution half-life (initial t1/2), 14.62 +/- 2.38 min; terminal half-life
      (terminal t1/2), 138.7 +/- 178.8 min; AUC 606 +/- 194 mg mL-1 min-1 (g liver)-1;
      elimination rate constant (Ke), 0.0135 +/- 0.012 min-1. Prior dosing with
      mefloquine did not affect halofantrine perfusate pharmacokinetic parameter
      estimates of Vd, Ke, initial and terminal t1/2 (P > 0.05). A single dose, short
      term (4-6 h) interaction showed significant changes in the perfusate clearance of
      halofantrine in mefloquine-pretreated livers using higher doses of halofantrine.
      Substantial changes were seen in bile production (P < 0.05) and biliary clearance
      (P < 0.05) of halofantrine in mefloquine-pretreated livers. These findings may
      have clinical implications in models utilizing multiple drug dosages or in
      patients with severe malaria who have disease-related cholestasis.

PMID- 8866338
TI  - 7-Ethoxy-3,4-dimethylcoumarin: a substrate for a cytochrome P450-mediated mono
      oxygenase activity that is highly induced by phenobarbitone and beta
      naphthoflavone.
AB  - The O-dealkylation of 7-ethoxy-3,4-dimethylcoumarin in rat liver microsomes was
      catalysed in a typical cytochrome P450-mediated reaction as judged by cofactor
      requirement and inhibition criteria, and displayed monophasic Michaelis-Menten
      kinetics. When measured at low substrate concentration, this activity was highly
      inducible by treatment with phenobarbitone or beta-naphthoflavone (44- and 78
      fold induction, respectively). These data indicate the potential usefulness of
      this activity as a probe for P4501A1- and P4502B-mediated activities. The O
      dealkylation of 7-methoxy- and 7-propoxy-3,4-dimethylcoumarin were much less
      inducible.

PMID- 8866339
TI  - Inhibitory effect of pentobarbital on biliary excretion of diclofenac in a rat
      liver perfusion system.
AB  - The effect of pentobarbital on the biliary excretion of diclofenac was
      investigated in a rat liver perfusion system following a pulse input of the drug.
      Without albumin in the perfusate, a trace amount of diclofenac was detected in
      the outflow from the liver (< 0.1%). The total biliary excretion of diclofenac
      (intact diclofenac plus its glucuronide) decreased from 23.8% (diclofenac 6.01,
      glucuronide 17.8%) to 16.3% (diclofenac 5.09, glucuronide 11.2%) with an increase
      in the perfusate concentration of pentobarbital from 0 to 2.5 micrograms mL-1. At
      pentobarbital concentrations exceeding 2.5 micrograms mL-1, the biliary excretion
      of diclofenac and its glucuronide (14% total diclofenac) was not reduced further.
      The mean local excretion times of both diclofenac and its glucuronide were
      approximately 17 min and were unchanged at all pentobarbital concentrations
      tested. The ratios of biliary excreted diclofenac and its glucuronide to total
      diclofenac were 22 and 78%, respectively, and these values were virtually
      constant at all concentrations of pentobarbital in the perfusate. These results
      suggest that the glucuronidation of diclofenac and the biliary excretion of its
      glucuronide are rapid processes and that pentobarbital blocks a step before
      glucuronidation.

PMID- 8866340
TI  - The disposition of aspirin and salicylic acid in the isolated perfused rat liver:
      the effect of normal and retrograde flow on availability and mean transit time.
AB  - The effect of changing the direction of perfusate flow from anterograde to
      retrograde on the disposition of acetylsalicylic acid (aspirin) and salicylic
      acid was studied in the single pass in-situ perfused rat liver. Mixtures of
      aspirin, [14C]salicylic acid and the inert reference solute [3H]sucrose were
      administered as boluses into the liver using red blood cell and albumin-free
      perfusate media at a flow rate of 30 mL min-1/liver. Hepatic availability (F),
      mean transit time (MTT) and normalized variance (CV2) for aspirin, preformed
      [14C]salicylic acid, salicylic acid produced from aspirin in the liver and
      [3H]sucrose were deduced from the outflow concentration profiles using
      statistical moment analysis. The values for F, MTT and CV2 for the solutes under
      anterograde perfusion were: aspirin (0.73 +/- 0.04, 15.13 +/- 2.01 s, 0.33 +/-
      0.09, n = 5), preformed [14C]salicylic acid (1.05 +/- 0.06, n = 12, 43.19 +/-
      2.21 s, 1.08 +/- 0.08, n = 5), salicylic acid from aspirin (0.33 +/- 0.05, 42.82
      +/- 9.16 s, 0.73 +/- 0.10, n = 5) and [3H]sucrose (1.05 +/- 0.05, 16.88 +/- 0.77
      s, 0.74 +/- 0.10, n = 5). The corresponding values for retrograde perfusions
      were: aspirin (0.73 +/- 0.02, 17.41 +/- 3.06 s, 0.32 +/- 0.09, n = 5), preformed
      [14C]salicylic acid (1.14 +/- 0.02, 44.42 +/- 3.16 s, 0.95 +/- 0.07, n = 5),
      salicylic acid from aspirin (0.33 +/- 0.09, 36.47 +/- 10.28 s, 0.58 +/- 0.05, n =
      5) and sucrose (1.01 +/- 0.04, 18.08 +/- 1.61 s, 0.76 +/- 0.15, n = 5). No
      significant differences in F or MTT were apparent between anterograde and
      retrograde perfusions for all solutes. The MTT and CV2 data for [14C]salicylic
      acid and salicylic acid produced from aspirin is suggestive of a permeability
      limitation for salicylic acid transport.

PMID- 8866341
TI  - Alterations in renal uptake kinetics of the xanthine derivative enprofylline in
      endotoxaemic mice.
AB  - The pharmacokinetics and renal uptake of enprofylline, which is primarily
      excreted into the urine by an active tubular secretion mechanism, were
      investigated in endotoxaemic mice by lipopolysaccharide isolated from Klebsiella
      pneumoniae. Lipopolysaccharide (1 mg kg-1) was infused 2 h before starting the
      examination, thereby inducing a decrease in the systemic clearance and an
      increase in the steady-state volume of distribution of enprofylline while
      inducing no changes in the urinary recovery (> 90%). The protein binding of
      enprofylline significantly decreased in the presence of lipopolysaccharide. Both
      the systemic clearance for unbound enprofylline and glomerular filtration rate
      decreased in the treated mice. A nonlinear relationship was found in both groups
      between the steady-state unbound plasma concentration and renal uptake of
      enprofylline after constant infusion for 1 h. The renal uptake rate of
      enprofylline decreased in the treated mice. Lipopolysaccaharide caused increases
      in the apparent maximum capacity for renal uptake (Vmax) from 17.3 to 32.2
      micrograms h-1 g-1 of kidney and in the Michaelis-Menten constant (Km) from 2.7
      to 21.7 micrograms mL-1 and decrease in the nonsaturable uptake rate constant
      (K4) from 0.87 to 0.43 mL h-1 g-1 of kidney. These results indicate that
      lipopolysaccharide decreases the renal tubular secretion of enprofylline by
      inducing a decrease in the renal uptake ability.

PMID- 8866342
TI  - Kinetics of bupivacaine after nicorandil treatment in mice.
AB  - Previous studies have reported interactions between potassium-channel agonists
      and bupivacaine. This study was designed to document possible changes in the
      pharmacokinetic behaviour of bupivacaine and its main metabolite, N
      desbutylbupivacaine, in mice after a single 1 mg kg-1 intraperitoneal injection
      of nicorandil. The kinetic variables of bupivacaine were determined after a
      single 20 mg kg-1 intraperitoneal dose of bupivacaine in controls (group 1) and
      in nicorandil-treated mice (group 2). The maximal concentration in the serum
      (Cmax 0.618 +/- 0.051 vs 0.408 +/- 0.041 microgram mL-1 for group 1 vs 2, P =
      0.01) and the area under the concentration curve (AUC 1.039 +/- 0.051 vs 0.758 +/
      0.072 microgram mL-1 h for group 1 vs 2, P = 0.013) of bupivacaine were
      significantly lower in nicorandil-treated mice, while CL (0.579 +/- 0.025 vs
      0.815 +/- 0.079 for group 1 vs 2, P = 0.022) and Vd (0.506 +/- 0.054 vs 0.981 +/-
      0.117 for group 1 vs 2, P = 0.1006) were increased in nicorandil-treated animals.
      The ratio of AUC for N-desbutylbupivacaine to AUC for bupivacaine, which may
      partially indicate the rate of metabolism, was higher in the presence of
      nicorandil (1.142 +/- 0.017 compared with 0.877 +/- 0.013, P = 0.0001). Our data
      may indicate an increased metabolism of bupivacaine in nicorandil-treated mice.
      These results do not explain the previously reported enhanced anaesthetic
      activity of bupivacaine in the presence of nicorandil, but may participate, at
      least in part, in the relative protective effect of nicorandil against the
      previously reported bupivacaine-induced toxicity.

PMID- 8866343
TI  - Interaction between fenbendazole and piperonyl butoxide: pharmacokinetic and
      pharmacodynamic implications.
AB  - The effect of the cytochrome P450 inhibitor, piperonyl butoxide on the
      pharmacokinetics and anthelmintic efficacy of the benzimidazole compound
      fenbendazole was studied in sheep and goats. Pretreatment of goats with the
      inhibitor caused a greater than three-fold increase in the relative
      bioavailability of fenbendazole and fenbendazole sulphoxide. A pharmacokinetic
      dose titration study was carried out in sheep with fenbendazole (5 mg kg-1) and
      piperonyl butoxide administered orally at 0, 15, 31, 63, 125 and 250 mg kg-1. The
      AUC of fenbendazole and the sulphoxide were significantly increased when
      fenbendazole was co-administered with piperonyl butoxide at dose rates equal to
      or higher than 31 mg kg-1. Peak plasma concentrations (Cmax) and mean residence
      time (MRT) were also significantly increased. The efficacy of the combination was
      assessed in sheep against two species of benzimidazole-resistant abomasal
      nematodes; Ostertagia circumcincta and Haemonchus contortus. The percentage
      reduction in the total number of O. circumcincta worms was 7.9% (fenbendazole)
      and 97.8% (fenbendazole-piperonyl butoxide). For H. contortus, the percentage
      reduction was 84.8% (fenbendazole) and 99.0% (fenbendazole-piperonyl butoxide).
      The in-vitro S-oxidation of fenbendazole and fenbendazole sulphoxide was studied
      using microsomal preparations from rat liver. Piperonyl butoxide inhibited
      significantly the sulphoxidation and sulphonation of fenbendazole. It was
      concluded that piperonyl butoxide inhibited the oxidative conversion of
      fenbendazole into inactive metabolites and this resulted in a potentiated
      anthelmintic action.

PMID- 8866344
TI  - Antidiarrhoeal activity of new thiazolidinones related to loperamide.
AB  - A series of thiazolidinones related to loperamide was synthesized and evaluated
      for antidiarrhoeal activity in mice, using the castor oil test. Of five compounds
      tested, antidiarrhoeal activity was found only for 2-(p-nitrophenyl)-3-?3-[(4-(p
      chlorophenyl)-4-hydroxy)piperidino]ethyl?- 1,3-thiazolidin-4-one. The compound
      was less active than loperamide (ED50 values = 48.7 (24.8-95.6) and 0.91 (0.24
      3.40) mg kg-1 respectively), but was also less toxic (LD50 values = 745.9 (545.2
      929.8) and 108.9 (85.5-138.7) mg kg-1, respectively). Its antidiarrhoeal activity
      was counteracted by naloxone. Our results support the hypothesis that this
      compound, like loperamide, is an opiate-receptor agonist.

PMID- 8866345
TI  - Molecular biological analysis of the effects of ginsenoside-Rb2 on albumin mRNA
      in streptozotocin-induced diabetic rats.
AB  - The mechanisms of the mRNA synthesis-promoting action of ginsenoside-Rb2, were
      investigated at the gene level. Rot analysis suggested that the previously
      reported increase in RNA polymerase activity as a result of administration of
      ginsenoside-Rb2 might be because of its effect on a specific gene. In this
      regard, albumin mRNA, which is expressed specifically in the liver, was assayed
      by northern blot hybridization using albumin cDNA in normal rats, diabetic
      control rats and diabetic rats given ginsenoside-Rb2. When the level of albumin
      mRNA in normal rats was set at 100, the level was reduced markedly to 32 in
      diabetic control rats. In contrast, in diabetic rats given ginsenoside-Rb2 the
      level was 0.54, significantly higher (69%) than that in diabetic rats given no
      ginsenoside-Rb2. In addition, poly(A)+RNA was purified from total RNA and
      subjected to hybridization, and poly(A)+RNA bands with different charges were
      measured by densitometry. The results of the measurement revealed changes
      dependent on the charge, and this was confirmed by autoradiography. We found no
      significant difference in the transcription activity of albumin mRNA, however, it
      showed only a tendency to increase. This suggests that ginsenoside-Rb2 has some
      effect on post-transcriptional regulation of the stability of mRNA itself. The
      results of Rot analysis suggest that ginsenoside-Rb2 affects a specific gene
      alone.

PMID- 8866346
TI  - The podiatric treatment of hallux abducto valgus and its associated condition,
      bunion, with Tagetes patula.
AB  - To assess the effectiveness of marigold therapy using Tagetes patula
      preparations, a double-blind placebo-controlled trial was designed to be carried
      out over a period of eight weeks. Sixty patients were entered in the trial.
      Twenty patients with bilateral hallux abducto valgus and its associated
      condition, bunion, were randomly selected from 37 subjects for group A. For group
      B, 40 patients with unilateral hallux abducto valgus and bunion were randomly
      selected from 69 subjects and subdivided into groups Ba and Bb. Patients with
      ulcerated conditions, those on medication and those who had undergone surgery for
      the condition were excluded. The results obtained were highly significant (P <
      0.001), suggesting that T. patula preparations, plus protective pad, were
      effective in reducing the width of the lesion and level of pain of hallux abducto
      valgus.

PMID- 8866347
TI  - Kinetics of desensitization induced by saturating flashes in toad and salamander
      rods.
AB  - 1. The suction pipette technique was used to examine the effect of a conditioning
      pre-flash on the saturation time (tsat) of a bright test flash (intensity 10,000
      250,000 isomerizations) delivered to intact salamander or toad rod outer
      segments. The conditioning flash was delivered 0-60 s before the test flash; its
      intensity was typically between six and sixty times dimmer than the test flash,
      and it was sufficient by itself to fully saturate the photocurrent. 2. A
      saturating pre-flash delivered before a saturating test flash reduced the tsat of
      the test flash. This was equivalent to a reduction in phototransduction gain
      (psi). 3. The pre-flash had little effect on tau zero the time constant of decay
      of the rate-limiting species in photoresponse inactivation (activated rhodopsin
      or the activated G-protein-phosphodiesterase complex). 4. The tsat declined
      exponentially as the separation time between a fixed intensity pre-flash and test
      flash was increased. The time constant (tau p) of decline in tsat was
      approximately 2.4s. The maximum reduction in tsat corresponded to a reduction in
      the apparent gain of phototransduction to approximately 0.10 of its original
      level. This exponential decline is consistent with a [Ca2+]i-mediated effect. 5.
      We conclude that the rate-limiting step in response inactivation and the step
      responsible for light-induced gain reduction constitute separate and distinct
      steps of the phototransduction cascade.

PMID- 8866348
TI  - Effects of repetitive tetanic stimulation at long intervals on excitation
      contraction coupling in frog skeletal muscle.
AB  - 1. Single skeletal muscle fibres of Xenopus frogs were used to investigate the
      possibility that excitation-contraction (E-C) coupling can be impaired under
      conditions of elevated intracellular free Ca2+ ([Ca2+]i). 2. Fibres were
      stimulated with a train of up to 200 tetani at 10 or 20s intervals; this long
      interval stimulation (LIS) scheme was chosen to minimize fatigue. After LIS,
      fibres were exposed to hypotonic Ringer solution for 5 min. At the end of LIS,
      force was about 90% of the original and the hypotonic challenge did not result in
      any force depression. 3. Caffeine, terbutaline and 2,5-di(tert-butyl)-1,4
      benzohydroquinone increased both basal and tetanic [Ca2+]i. In ten out of
      thirteen fibres, the presence of any of these drugs during LIS resulted in a
      force reduction to about 10% of the control when fibres were returned to normal
      Ringer solution after the hypotonic challenge. Force production was severely
      depressed for at least 20 min and then recovered to control levels within 120
      min. 4. Neither protease inhibitors nor a scavenger of reactive oxygen species
      prevented the impairment of E-C coupling. 5. It is concluded that after a period
      of elevated [Ca2+]i, E-C coupling in frog skeletal muscle becomes sensitive to
      the mechanical stress induced by exposure to hypotonic solution. The underlying
      molecular basis for this remains unclear.

PMID- 8866349
TI  - Modulation of K+ conductances by Ca2+ and human chorionic gonadotrophin in Leydig
      cells from mature rat testis.
AB  - 1. Although the control of steroidogenic activity of the Leydig cell by the
      peptides luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) is
      clearly mediated by cAMP, the extent to which Ca2+ controls the Leydig cell
      function is less well defined. In the present study, the whole-cell configuration
      of the patch-clamp technique was used to investigate the modulation of potassium
      conductances by calcium and hCG, in the Leydig cells from mature rat testis. 2.
      In symmetrical glutamate solutions, depolarizations elicited outwardly rectifying
      currents, which were mainly carried by potassium and were blocked by
      tetraethylammonium and 4-aminopyridine. For values of [Ca2+]i below 10(-8) M,
      transient currents of low amplitudes, insensitive to charybdotoxin (CTX) and
      iberiotoxin (IBTX), were activated above -40 mV. For [Ca2+]i values of 10(-7) M
      and above, noisy currents with slow activation kinetics were activated above 0
      mV. These currents were sustained and were sensitive to CTX and IBTX. 3. Both
      current types were modulated by intracellular calcium. Ionomycin and a [Ca2+]i
      elevation in the range from 10(-9) to 10(-7) M, both inhibited the CTX
      insensitive currents, whereas a rise in the calcium concentration above 10(-7) M
      increased the amplitude and shifted the threshold of activation of the CTX
      sensitive currents to less positive levels. 4. hCG (1-50 i.u. ml-1), in
      conditions where the chloride currents were strongly inhibited by 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulphonic acid (SITS), induced a partial inhibition
      of the CTX-insensitive currents but was unable to increase the CTX-sensitive
      currents. 5. No voltage-sensitive calcium current was recorded in control or hCG
      stimulated cells. 6. The results indicate that hCG inhibits one kind of Ca(2+)
      modulated channel, perhaps as a result of a moderate [Ca2+]i rise, but is unable
      to increase the intracellular Ca2+ concentration to the range in which large
      conductance Ca(2+)-dependent channels are activated.

PMID- 8866350
TI  - Oxidized glutathione mediates cation channel activation in calf vascular
      endothelial cells during oxidant stress.
AB  - 1. The oxidant, tert-butylhydroperoxide (tBuOOH) depolarizes calf pulmonary
      artery endothelial cells by activating a non-selective cation channel. To
      identify the molecular mediator of channel activation during oxidant stress, the
      patch-clamp technique was used to compare tBuOOH-induced changes in membrane
      potential and channel activity with those induced by oxidized glutathione (GSSG),
      a cytosolic product of oxidant metabolism. 2. When recording pipettes contained
      GSSG (2 mM), whole-cell zero-current potential measured immediately following
      pipette break-in was not different from control values (-57 mV). However, within
      20 min of break-in, zero-current potential was depolarized to -7 mV. The time
      course of depolarization was dependent on the concentration of GSSG and was
      accelerated by inhibition of GSSG metabolism. 3. In excised membrane patches,
      channels were activated by internal GSSG, but not by internal tBuOOH, reduced
      glutathione (GSH), or external GSSG. Channels were equal in size (28 pS) and in
      ionic selectivity to those activated by incubation of intact cells with tBuOOH.
      As little as 20 microM GSSG was sufficient to maximally activate channels.
      However, the time course of channel activation was concentration dependent
      between 20 microM and 2 mM GSSG. 4. Channel activation by GSSG was reversed by
      GSH and by increasing the [GSH]:[GSSG] ratio. Likewise, channel activation by pre
      incubation of intact cells with tBuOOH was reversed by GSH applied after patch
      excision. 5. These results strongly suggest that GSSG is an endogenous
      intracellular mediator of channel activation and depolarization during oxidant
      stress.

PMID- 8866351
TI  - External-anion-dependent anionic current in blastoderm cells of early medaka fish
      embryos.
AB  - 1. Anionic current was studied by a whole-cell variation of the patch-clamp
      technique in blastoderm cells dissociated from medaka (Oryzias latipes) embryos
      at the early blastula stage. The blastoderm cells were mechanically dissociated
      without using proteolytic enzymes. 2. The anionic current was deactivated by
      hyperpolarizing steps. The steady-state current-voltage (I-V) relationship of the
      anion current was accurately represented by the Boltzmann relation with z = 1.01
      +/- 0.02 (+/- S.E.M., n = 4) for voltage-dependent activation when internal
      calcium ions were buffered at 100 nM by BAPTA-Ca2+ buffer. 3. When the internal
      calcium concentration was reduced to 10 nM, this anionic current became an
      external-calcium-dependent current and was remarkably decreased by removal of
      external calcium ions. Furthermore, this anionic current was almost abolished
      when the internal calcium concentration was greatly reduced by chelating Ca2+
      ions with 10 mM BAPTA. 4. This current was not affected by replacing external Na+
      with TEA+ or N-methyl-D-glucamine. The reversal potentials shifted by +58.6 mV
      for a 10-fold decrease in the external Cl-concentration. External Cl-ions were
      substituted with various anions and respective current-reversal potentials were
      measured. The order of permeability was I- > Br- > Cl- > F-. Both the outward and
      inward currents almost disappeared in external Cl(-)-free solutions. 5. The
      voltage dependency of the anionic current shifted in a positive direction with
      the reduction in the external Cl- concentration, the potentials at which half the
      channels were activated (V 1/2) being -59.8 +/- 1.2 mV (n = 4), -40.7 +/- 0.8 mV
      (n = 4), -14.9 +/- 0.7 mV (n = 4), and -0.7 +/- 0.6 mV (n = 4) for 135, 90, 67,
      and 45 mM Cl-, respectively. This implies that the inward current, brought by
      efflux of internal anions, decreases with reductions in the external Cl-
      concentration. In the presence of external 135 mM Br-, the voltage dependency of
      the anionic current shifted in the negative direction (V 1/2 = -84.5 +/- 1.0 mV
      and z = 0.91 +/- 0.02 (n = 3)) in comparison with that in the external Cl-
      medium. It further shifted in the negative direction in the presence of 135 mM I-
      (V 1/2 = -93.8 +/- 1.5 mV and z = 0.85 +/- 0.03 (n = 3)). The inward current of
      the anion channel is considered to be affected by both the type and the
      concentration of external halide ions. 6. At the beginning of the blastula stage,
      the blastocoel cavity is formed for the first time. A mechanism is necessary to
      transport ions to the cavity without losing them to pond water outside the
      embryos. Since this anion channel is external-anion dependent, the current cannot
      be activated in the membrane facing the pond water, where concentrations of
      anions are much lower than those of the intracavernous solution. Only after
      blastocoel formation are blastoderm cells first exposed to the extracellular
      fluid with high ionic concentrations. Then, the anion channel would become
      effective for maintaining the Cl- equilibrium potential.

PMID- 8866352
TI  - Novel chloride-dependent acid loader in the guinea-pig ventricular myocyte: part
      of a dual acid-loading mechanism.
AB  - 1. The fall of intracellular pH (pH1) following the reduction of extracellular pH
      (pH0) was investigated in guinea-pig isolated ventricular myocytes using
      intracellular fluorescence measurements of carboxy-SNARF-1 (to monitor pH1). Cell
      superfusates were buffered either with a 5% CO2-HCO3- system or were nominally
      CO2-HCO3-free. 2. Reduction of pH0 from 7.4 to 6.4 reversibly reduced pH1 by
      about 0.4 pH units, independent of the buffer system used. 3. In HCO3(-)-free
      conditions, acid loading in low pH0 was not dependent on Na(+)-H+ exchange or on
      the presence of Na+. It was unaffected by high-K+ solution, by voltage-clamp
      depolarization, by various divalent cations (Zn2+, Cd2+, Ni2+ and Ba2+) and by
      the organic Ca2+ channel blocker diltiazem, thus ruling out proton influx through
      H(+)-or Ca(2+)-conductance channels or influx via a K(+)-H+ exchanger. The fall
      also persisted in the presence of glycolytic inhibitors, or the lactate transport
      inhibitor, alpha-cyano-4-hydroxy cinnamate. 4. In HCO3(-)-free conditions, acid
      loading in low pH0 was reversibly inhibited (by up to 85%) by Cl(-)0 removal and
      was slowed by the stilbene drug DBDS (dibenzamidostilbene disulphonic acid). In
      contrast, the Cl(-)-HCO3-exchange inhibitor DIDS (4,4'-diisothiocyanatostilbene
      2,2'-disulphonic acid) had no inhibitory effect. Acid loading is therefore
      mediated by a novel Cl(-)-dependent, acid influx pathway. 5. After switching to
      CO2-HCO3(-)-buffered conditions, acid loading was doubled. It was still not
      inhibited by Na(+)-free or high-K+ solutions but was once again inhibited (by
      78%) in Cl(-)-free solution. The HCO3(-)-stimulated fraction of acid loading was
      inhibited by DIDS. 6. We propose a model of acid loading in the cardiomyocyte
      which consists of two parallel carriers. One is Cl(-)-HCO3-exchange, while we
      suggest the other to be a novel Cl(-)-OH-exchanger (although we do not rule out
      the alternative configuration of H(+)-Cl-co-influx). The proposed dual acid
      loading mechanism accounts for most of the sensitivity of pH1 to a fall of pH0.

PMID- 8866353
TI  - Open channel and competitive block of the embryonic form of the nicotinic
      receptor of mouse myotubes by (+)-tubocurarine.
AB  - 1. Embryonic-like nicotinic channels were studied in mouse myotubes. Channel
      currents were measured by patch clamping outside-out excised patches to which
      pulses of agonists and drugs could be applied by a liquid filament switch. The
      holding potential of the patches was generally around-10 to-40 mV. 2. Pulses of
      100 microM or 1 mM acetylcholine (ACh) elicited average channel currents which
      reached a maximum open probability of 0.93 within 0.5-1.0 ms, decayed with a time
      constant of desensitization of 20-80 ms, and fell rapidly to zero at the end of
      the pulse. When such pulses together with increasing concentrations of (+)
      tubocurarine (TC) were applied to outside-out patches, the time constant of
      current decay, tau, decreased beginning at concentrations of TC added to the test
      solution of > 10 microM, and the peak amplitude of the current decreased markedly
      at concentrations of TC of > 30 microM due to an open channel block of nicotinic
      channels by TC. 3. When the outside-out patches were pre-incubated with TC, the
      peak current elicited by pulses of 100 microM ACh or 1 mM ACh + TC decreased
      markedly, beginning with concentrations of TC > 30 nM due to a competitive block.
      4. The results could be quantitatively modelled by computer calculations based on
      a circular reaction scheme containing desensitization. TC blocked the open state
      as well as the unliganded closed state of the embryonic-like nicotinic receptors
      of mouse myotubes. Also the blocked open channel was subject to desensitization.
      5. The rates of block and unblock of the open channel were 3 x 10(6) M-1 S-1 and
      0.8 S-1, respectively, and those of the competitive block were 0.5 x 10(6) M-1 S
      1 and 0.1 S-1, respectively (at 20 degrees C).

PMID- 8866354
TI  - Dopamine D1-like receptor-mediated presynaptic inhibition of excitatory
      transmission onto rat magnocellular basal forebrain neurones.
AB  - 1. Excitatory postsynaptic currents (EPSCs) following focal afferent stimulation
      were recorded from patch-clamped magnocellular neurones in a thin-slice
      preparation of the rat basal forebrain. Evoked EPSCs had a mean decay time
      constant of 3.81 +/- 0.09 ms and were reversibly blocked by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX, 5 microM). 2. Bath-applied dopamine (DA)
      reduced evoked EPSC amplitude by up to 54.2 +/- 2.3% with an IC50 of 19.9 microM
      in normal Krebs solution (2.5 mM Ca2+, 1.2 mM Mg2+) without effect on
      postsynaptic holding current. 3. DA (30 microM) reduced the mean frequency of
      spontaneous miniature EPSCs recorded in 0.5 microM tetrodotoxin without affecting
      their mean amplitude, rise time or decay time constant. This effect was
      diminished by 100 microM Cd2+. 4. The effect of DA on evoked EPSCs was mimicked
      by the D1-like receptor agonist, SKF 81297 (IC50 25.6 microM), but not by the D2
      like receptor agonist R(-)-TNPA (30 microM) or (-)-quinpirole (30 microM), and
      was antagonized by the D1-like receptor antagonist R(+)-SCH 23390 (estimated
      dissociation constant KB = 1.7 microM) but not by the D2-like receptor antagonist
      S(-)-eticlopride (10 microM). 5. Forskolin (10 microM) reduced evoked EPSCs to
      approximately 60% of the control amplitude, and occluded the effect of subsequent
      application of DA. 6. These results suggest that glutamatergic afferents to
      magnocellular basal forebrain neurones possess presynaptic D1-like DA receptors,
      and that activation of these receptors reduces excitatory glutamatergic
      transmission, probably via an adenylyl cyclase-dependent pathway.

PMID- 8866355
TI  - Increased neuronal excitability during depolarization-induced suppression of
      inhibition in rat hippocampus.
AB  - 1. Depolarization-induced suppression of inhibition (DSI) is a form of plasticity
      of gamma-amino-butyric acid (GABAA)-mediated (henceforth 'GABAergic') responses
      in the CNS. We made whole-cell recordings from CA1 pyramidal neurons to
      investigate the effects of DSI on excitatory synaptic transmission in the
      hippocampal slice preparation. 2. Significant enhancement of the voltage-clamped
      excitatory postsynaptic current (EPSC) occurs during DSI of the temporally
      overlapping inhibitory postsynaptic current. With high levels of calcium
      chelators in the pipette solution, or bath application of bicuculline, EPSC
      enhancement is blocked, suggesting that it results from DSI and that the DSI
      process selectively affects GABAergic, but not glutamatergic, transmission. 3.
      The probability of synaptically evoked action potential firing is increased
      during DSI under current clamp. DSI could influence other excitatory phenomena as
      well.

PMID- 8866356
TI  - Sr2+ and quantal events at excitatory synapses between mouse hippocampal neurons
      in culture.
AB  - 1. Whole-cell recording from pairs of adjacent mouse hippocampal neurons in
      culture was used to study the quantal properties of action potential-evoked
      excitatory synaptic transmission and to demonstrate the use of Sr2+ in
      quantifying those properties. 2. In the presence of extracellular Sr2+,
      excitatory postsynaptic currents (EPSCs) were followed by an after-discharge of
      miniature excitatory postsynaptic currents (mEPSCs) lasting 1-2 s and generated
      by evoked asynchronous release of presynaptic quanta of transmitter. Like the
      EPSC of which it is thought to be an extension, the after-discharge was modulated
      by procedures expected to modulate Sr2+ influx into the nerve terminal. The
      number of mEPSCs in the after-discharge was decreased by increasing extracellular
      [Mg2+], and increased by increasing extracellular [Sr2+] or increasing the number
      of action potentials used to evoke the after-discharge. 3. EPSCs recorded in
      media containing either 1 mM Ca2+ or 6 mM Sr2+ were of similar amplitude. Adding
      Sr2+ to low-Ca2+ media increased EPSC amplitude, while adding Sr2+ to high-Ca2+
      media lowered EPSC amplitude. These results suggest that extracellular Sr2+ is
      less effective than Ca2+ in supporting quantal release. 4. The levels of
      extracellular Ca2+, Mg2+ and Sr2+ were adjusted so that most after-discharge
      mEPSCs were discrete and comparable in numbers to the quantal events that
      contributed to the corresponding evoked EPSCs. In a series of twenty-five pairs
      of neurons, the mean amplitude of mEPSCs recorded at -80 mV was 35 +/- 10 pA and
      the mean coefficient of variation was 0.50 +/- 0.10 (range, 0.26-0.62). The mEPSC
      amplitude histogram was positively skewed. 5. In ten pairs of neurons, the mean
      and variance of EPSCs and mEPSCs and quantal content were determined from samples
      of more than 100 evoked events (in superfusion solutions containing (mM): 0.5
      Ca2+, 2 Sr2+ and 10 Mg2+) and mean quantal content was determined from the ratio
      of amplitudes of the mean EPSC and mEPSC. A binomial quantal analysis produced
      values of 2-12 for Napp (apparent number of independent synapses) and 0.25-0.75
      for Papp (apparent probability of releasing a quantum at one of those synapses).
      These parameters predicted the number of observed failures. The observed
      coefficient of variation for quantal content predicted the observed coefficient
      of variation of the EPSC amplitude when the coefficient of variability of quantal
      amplitude of after-discharge mEPSCs was taken into account. 6. In six pairs of
      neurons, where more than 250 evoked events were recorded, the observed amplitude
      histogram for EPSCs could be approximated by a predicted amplitude distribution
      generated from the estimated binomial parameters and an empirical function
      describing the amplitude distribution of after-discharge mEPSCs. 7. The
      observation that parameters derived from mEPSCs that contribute to the Sr(2+)
      generated after-discharge can predict the shape of the EPSC amplitude
      distribution and a quantal content consistent with the observed failure rate and
      EPSC amplitude variance, suggests that this subset of mEPSCs has the same
      properties as the quantal events released around the time of the peak of the
      corresponding EPSCs. The use of Sr2+ to evoke after-discharges of mEPSCs should
      allow unambiguous determination of the extent to which modification of synaptic
      strength is pre- or postsynaptic.

PMID- 8866357
TI  - A role for synaptic and network plasticity in controlling epileptiform activity
      in CA1 in the kainic acid-lesioned rat hippocampus in vitro.
AB  - 1. Stimulation of the surviving afferents in the stratum radiatum of the CA1 area
      in kainic acid-lesioned hippocampal slices produced graded epileptiform activity,
      part of which (> 20%) involved the activation of N-methyl-D-aspartate (NMDA)
      receptors. There was also a failure of synaptic inhibition in this region. In
      this preparation, we have tested the effects of low-frequency stimulation (LFS; 1
      Hz for 15 min) on synaptic responses and epileptiform activity. 2. LFS resulted
      in long-term depression (LTD) of excitatory synaptic potentials (EPSPs), long
      term decrease of population spike amplitudes (PSAs) and EPSP-spike (E-S)
      potentiation. Evoked epileptiform activity was reduced but neurons had a higher
      probability of discharge. LTD could be reversed by subsequent tetanic stimulation
      whereas E-S dissociation remained unchanged. Synaptic and network responses could
      be saturated towards either potentiation or depression. However, E-S potentiation
      was maximal following the first conditioning stimulus. 3. NMDA receptor-mediated
      responses were pharmacologically isolated. LFS resulted in LTD of synaptic
      responses, long-term decrease of PSAs and E-S depression. These depressions could
      not be reversed by subsequent tetanic stimulation. alpha-Amino-3-hydroxy-5
      methylisoxazolepropionic acid (AMPA) and NMDA receptor-mediated responses were
      then measured in isolation before and following conditioning stimuli. LFS was
      shown to simultaneously produce LTD of AMPA and NMDA receptor-mediated responses.
      E-S potentiation of the AMPA component and E-S depression of the NMDA component
      occurred coincidentally. 4. LTD of AMPA and NMDA receptor-mediated responses were
      shown to be NMDA dependent. In contrast, E-S potentiation and depression occurred
      even when NMDA receptors were pharmacologically blocked. 5. These findings
      indicate that synaptic responses could be modified bidirectionally in the CA1
      area of kainic acid-lesioned rat hippocampus in an NMDA receptor-dependent
      manner. However, E-S dissociations were independent of the activation of NMDA
      receptors, hinting at mechanisms different from those of synaptic LTD. We suggest
      that changes in E-S coupling were caused by a modification of the firing
      threshold of the CA1 pyramidal neurons. Furthermore, the firing mechanisms
      controlling NMDA and AMPA receptor-mediated network activity appeared to be
      different. The possible use of LFS applied to the hippocampus as a clinical
      intervention to suppress epileptiform activity is discussed.

PMID- 8866358
TI  - Effects of background noise on the response of rat and cat motoneurones to
      excitatory current transients.
AB  - 1. We studied the responses of rat hypoglossal motoneurones to excitatory current
      transients (ECTs) using a brainstem slice preparation. Steady, repetitive
      discharge at rates of 12-25 impulses s-1 was elicited from the motoneurones by
      injecting long (40 s) steps of constant current. Poisson trains of the ECTs were
      superimposed on these steps. The effects of additional synaptic noise was
      simulated by adding a zero-mean random process to the stimuli. 2. We measured the
      effects of the ECTs on motoneurone discharge probability by compiling
      peristimulus time histograms (PSTHs) between the times of occurrence of the ECTs
      and the motoneurone spikes. The ECTs produced modulation of motoneurone discharge
      similar to that produced by excitatory postsynaptic currents. 3. The addition of
      noise altered the pattern of the motoneurone response to the current transients:
      both the amplitude and the area of the PSTH peaks decreased as the power of the
      superimposed noise was increased. Noise tended to reduce the efficacy of the
      ECTs, particularly when the motoneurones were firing at lower frequencies.
      Although noise also increased the firing frequency of the motoneurones slightly,
      the effects of noise on ECT efficacy did not simply result from noise-induced
      changes in mean firing rate. 4. A modified version of the experimental protocol
      was performed in lumbar motoneurones of intact, pentobarbitone-anaesthetized
      cats. These recordings yielded results similar to those obtained in rat
      hypoglossal motoneurones in vitro. 5. Our results suggest that the presence of
      concurrent synaptic inputs reduces the efficacy of any one input. The
      implications of this change in efficacy and the possible underlying mechanisms
      are discussed.

PMID- 8866359
TI  - Reversible inactivations of the cerebellum prevent the extinction of conditioned
      nictitating membrane responses in rabbits.
AB  - 1. Studies show that reversible inactivation of the anterior interpositus nucleus
      (AIP) of the cerebellum with muscimol (a GABAA agonist) prevents acquisition of
      the classically conditioned nictitating membrane response (NMR) in the rabbit.
      Here, we have used reversible inactivations of the AIP with muscimol to
      investigate the role of the cerebellum in the extinction of this response. 2.
      Experimental subjects were implanted with cannulae targeted to the AIP, through
      which muscimol could be infused via an injector cannula. This experiment was
      divided into three phases lasting 4 days, separated by 3 day intervals.
      Experimental and unoperated control subjects received acquisition training in
      phase 1; in phases 2 and 3 they received extinction training. 3. Presentation of
      the conditioned stimulus (CS) alone in phase 2 produced normal extinction in
      control subjects. Muscimol inactivation of the AIP in experimental subjects
      during phase 2 prevented extinction of conditioned responses (CRs), shown by
      initial high CR frequency in the first post-drug session of phase 3, which then
      extinguished in a manner indistinguishable from controls in phase 2. 4. Our
      findings support the suggestion that similar cerebellar circuitry is engaged in
      acquisition and extinction of NMR conditioning.

PMID- 8866360
TI  - Accumulation of intracellular HCO3- by Na(+)-HCO3- cotransport in interlobular
      ducts from guinea-pig pancreas.
AB  - 1. Short segments of interlobular duct were microdissected from guinea-pig
      pancreas following enzymatic digestion. After overnight culture, intracellular pH
      (pH1) and Na+ concentration ([Na+]i) were measured by microfluorometry in duct
      cells loaded with either the pH-sensitive fluoroprobe 2'7'-bis(2-carboxyethyl)
      5(6)-carboxyfluorescein (BCECF) or the sodium-binding benzofuran isophthalate
      (SBFI). 2. The transporters responsible for maintaining pHi above equilibrium
      were investigated by using the NH4Cl pulse technique to acid load the cells. In
      the absence of HCO3-/CO2, the recovery of pH1 was Na+ dependent, abolished by 0.2
      mM amiloride and by 10 microM N-methyl-N-isobutylamiloride and was therefore
      attributed to Na(+)-H+ exchange. 3. In the presence of HCO3-/CO2, amiloride only
      partially inhibited the recovery from acid loading. The amiloride-insensitive
      component was abolished by 0.5 mM H2DIDS and unaffected by depletion of
      intracellular Cl- and was therefore attributed to Na(+)-HCO3- cotransport. 4.
      Stimulation with 10 nM secretin did not cause a significant change in pH1 despite
      a significant increase in HCO3- efflux. However, in the presence of secretin,
      addition of 0.5 mM H2DIDS caused a decline in pH1 that was three times more rapid
      than that obtained with 0.2 mM amiloride. 5. In secretin-stimulated ducts, Na+
      uptake increased when HCO3-/CO2 was added to the bath and this increase was
      strongly inhibited by 0.5 mM H2DIDS. 6. We conclude that Na(+)-HCO3- cotransport
      contributes approximately 75% of the HCO3- taken up by guinea-pig pancreatic duct
      cells during stimulation with secretin. It is proposed that electrical coupling
      between HCO3- efflux at the luminal membrane and electrogenic Na(+)-HCO3-
      cotransport at the basolateral membrane explains why secretin causes little
      change in pH1.

PMID- 8866361
TI  - Bicarbonate secretion in interlobular ducts from guinea-pig pancreas.
AB  - 1. The transport of HCO3- across the luminal membrane of pancreatic duct cells
      was studied by monitoring the luminal pH of isolated guinea-pig interlobular
      ducts after microinjection of an extracellular fluoroprobe, the dextran conjugate
      of 2'7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF-dextran). Luminal Cl-
      concentration was also measured by microfluorometry following microinjection of
      the dextran conjugates of 6-methoxy-N-(4-aminoalkyl)quinolinium bromide (ABQ
      dextran) and Cl-NERF (Cl-NERF-dextran). 2. When HCO3-/CO2 was admitted to the
      bath, a transient acidification of the duct lumen was observed, followed by a
      marked alkalinization. The latter was abolished when the luminal Cl-
      concentration was reduced to 25-35 mM by replacement with glucuronate and may,
      therefore, be attributed to Cl(-)-HCO3- exchange at the luminal membrane. 3.
      Secretin, forskolin and acetylcholine stimulated HCO3- secretion into the lumen
      even when the luminal Cl- concentration was reduced to approximately 7 mM.
      Furthermore, agonist-evoked HCO3- secretion was not inhibited by luminal
      glibenclamide, dihydro-4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (H2DIDS)
      or 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB). These observations are
      not easily reconciled with HCO3- transport across the luminal membrane being
      mediated by Cl(-)-HCO3- exchange in parallel with a Cl- conductance. 4. Agonist
      stimulated HCO3- secretion was blocked by omitting Na+ from the bath but not by
      addition of N-methyl-N-isobutylamiloride (MIA) or bafilomycin A1. This supports
      our previous conclusion that HCO3- entry into duct cells from the extracellular
      fluid requires Na+ but is not dependent on Na(+)-H+ exchange or vacuolar-type
      H(+)-ATPase activity. 5. The three actions of secretin on guinea-pig pancreatic
      duct cells described in this and the accompanying paper - stimulation of a
      relatively Cl(-)-insensitive luminal HCO3- efflux pathway, stimulation of
      basolateral Na(+)-HCO3- cotransport, and lack of effect on intracellular pH-
      require the current model of pancreatic HCO3- secretion to be modified.

PMID- 8866362
TI  - A novel physiological function for platelet-derived growth factor-BB in rat
      dermis.
AB  - 1. The present experiments describe a role for platelet-derived growth factor-BB
      and cellular adhesion receptors towards extracellular matrix molecules (beta 1
      integrins) in control of interstitial fluid pressure (Pif). 2. Pif was measured
      in rat skin with sharpened glass capillaries (3-7 microns) connected to a
      servocontrolled counter-pressure system. 3. The collagen and laminin-binding
      alpha 2 beta 1-integrin is involved in the control of Pif since subdermal
      injection (5 microliters) of monoclonal hamster anti-rat alpha 2 beta 1-integrin
      IgG (anti-alpha 2 beta 1) resulted in increased negativity of Pif. Control Pif
      averaged -0.88 +/- 0.23 mmHg (+/- S.D.) and decreased to -2.50 +/- 0.35 mmHg (P <
      0.05) and -3.88 +/- 1.45 mmHg (P < 0.05) at anti-alpha 2 beta 1 concentrations of
      0.56 and 1.12 mg ml-1, respectively. 4. The effect of anti-alpha 2 beta 1 was
      abolished when platelet-derived growth factor-BB (PDGF-BB) (200 ng ml-1) was
      injected together with anti-alpha 2 beta 1. 5. The time- and dose-responses of
      PDGF-BB to counteract increased negativity of Pif were studied further using
      dextran anaphylaxis as an experimental model inducing increased negativity of Pif
      in skin. Control Pif averaged -0.33 +/- 0.43 mmHg and fell to -4.10 +/- 1.47 mmHg
      within 10 min after dextran (P < 0.01). Subsequent subdermal injection of PDGF-BB
      at 200 ng ml-1 normalized Pif in 10-20 min which became -1.37 +/- 1.23 mmHg (P <
      0.01 versus dextran, P > 0.05 versus control). PDGF-BB had little or no effect at
      50 ng ml-1. PDGF-AA and basic fibroblast growth factor had no effect on Pif. 6.
      The in vivo function reported for PDGF-BB has not been described previously and
      provides further evidence for active participation of connective tissue cells in
      control of Pif by altering tension on extracellular matrix structures.

PMID- 8866363
TI  - Contribution of oxygen-sensitive neurons of the rostral ventrolateral medulla to
      hypoxic cerebral vasodilatation in the rat.
AB  - 1. We sought to determine whether hypoxic stimulation of neurons of the rostral
      ventrolateral reticular nucleus (RVL) would elevate regional cerebral blood flow
      (rCBF) in anaesthetized paralysed rats. 2. Microinjection of sodium cyanide
      (NaCN; 150-450 pmol) into the RVL rapidly (within 1-2 s), transiently, dose
      dependently and site-specifically elevated rCBF1 measured by laser Doppler
      flowmetry, by 61.3 +/- 22.1% (P < 0.01), increased arterial pressure (AP; +30 +/-
      8 mmHg; P < 0.01)1 and triggered a synchronized 6 Hz rhythm of EEG activity. 3.
      Following cervical spinal cord transection, NaCN and also dinitrophenol (DNP)
      significantly (P < 0.05) elevated rCBF and synchronized the EEG but did not
      elevate AP; the response to NaCN was attenuated by hyperoxia and deepening of
      anaesthesia. 4. Electrical stimulation of NaCN-sensitive sites in the RVL in
      spinalized rats increased rCBF measured autoradiographically with 14C
      iodoantipyrine (Kety method) in the mid-line thalamus (by 182.3 +/- 17.2%; P <
      0.05) and cerebral cortex (by 172.6 +/- 15.6%; P < 0.05) regions, respectively,
      directly or indirectly innervated by RVL neurons, and in the remainder of the
      brain. In contrast regional cerebral glucose utilization (rCGU), measured
      autoradiographically with 14C-2-deoxyglucose (Sokoloff method), was increased in
      proportion to rCBF in the mid-line thalamus (165.6 +/- 17.8%, P < 0.05) but was
      unchanged in the cortex. 5. Bilateral electrolytic lesions of NaCN sensitive
      sites of RVL, while not altering resting rCBF or the elevation elicited by
      hypercarbia (arterial CO2 pressure, Pa,CO2, approximately 69 mmHg), reduced the
      vasodilatation elicited by normocapnic hypoxaemia (arterial O2 pressure, Pa,O2,
      approximately 27 mmHg) by 67% (P < 0.01) and flattened the slope of the Pa,O2
      rCBF response curve. 6. We conclude that the elevation of rCBF produced in the
      cerebral cortex by hypoxaemia is in large measure neurogenic, mediated trans
      synaptically over intrinsic neuronal pathways, and initiated by excitation of
      oxygen sensitive neurons in the RVL.

PMID- 8866364
TI  - Red nucleus lesions abolish the biphasic respiratory response to isocapnic
      hypoxia in decerebrate young rabbits.
AB  - 1. The respiratory response to isocapnic hypoxia (inspired O2 fraction (FI,O1),
      0.1-0.12) was measured in twelve vagotomized, paralysed, artificially ventilated
      young rabbits (aged 26.6 +/- 0.4 days), following pre-collicular decerebration.
      Phrenic nerve efferent activity was used as an index of central respiratory
      output (RO). In hypoxia RO increased after 1-2 min (phase 1) but decreased over
      the subsequent 3-4 min to, or below, the pre-hypoxic control level (phase 2). 2.
      We used electrical stimulation to target areas in the mesencephalon which inhibit
      RO. Profiles of the response to stimulation were determined in a grid of
      electrode penetrations made mediolaterally and rostrocaudally at the level of the
      superior colliculi, in normoxia. Histology confirmed that stimulation in the red
      nucleus (RN) inhibited RO profoundly. 3. Electrolytic lesions were made
      bilaterally in RN inhibitory sites or in adjacent areas. The respiratory response
      to isocapnic hypoxia was measured again post-lesioning. 4. In six rabbits with
      bilateral lesions in the RN, phase 2 of the respiratory response was abolished
      and RO remained elevated throughout the hypoxic exposure. However, in six rabbits
      with unilateral lesions in the RN, or with bilateral lesions placed in areas
      outside the RN that did not inhibit RO on electrical stimulation, the respiratory
      response remained biphasic. 5. In both groups of animals, blood pressure
      increased during 1-3 min of hypoxia before decreasing to pre-hypoxic levels. This
      cardiovascular response remained biphasic irrespective of whether animals showed
      a biphasic respiratory response or a sustained increase in RO after lesioning. 6.
      We conclude that structures within the RN are crucial to the mechanism producing
      a fall in RO during isocapnic hypoxaemia in the neonate.

PMID- 8866365
TI  - The effect of low-dose acetazolamide on the ventilatory CO2 response curve in the
      anaesthetized cat.
AB  - 1. The effect of 4 mg kg-1 acetazolamide (I.V.) on the slope (S) and intercept on
      the Pa,CO2 axis (B) of the ventilatory CO2 response curve of anaesthetized cats
      with intact or denervated carotid bodies was studied using the technique of
      dynamic end-tidal forcing. 2. This dose did not induce an arterial-to-end-tidal
      PCO2 (P(a-ET),CO2) gradient, indicating that erythrocytic carbonic anhydrase was
      not completely inhibited. Within the first 2 h after administration, this small
      dose caused only a slight decrease in mean standard bicarbonate of 1.8 and 1.7
      mmol l-1 in intact (n = 7) and denervated animals (n = 7), respectively. Doses of
      acetazolamide larger than 4 mg kg-1 (up to 32 mg kg-1) caused a significant
      increase in the P(a-ET),CO2 gradient. 3. In carotid body-denervated cats, 4 mg kg
      1 acetazolamide caused a decrease in the CO2 sensitivity of the central
      chemoreflex loop (Sc) from 1.52 +/- 0.42 to 0.96 +/- 0.32 l min-1 kPa-1 (mean +/-
      S.D.) while the intercept on the Pa,CO2 axis (B) decreased from 4.5 +/- 0.5 to
      4.2 +/- 0.7 kPa. 4. In carotid body-intact animals, 4 mg kg-1 acetazolamide
      caused a decrease in the CO2 sensitivity of the peripheral chemoreflex loop (Sp)
      from 0.28 +/- 0.18 to 0.19 +/- 0.12 l min-1 kPa-1. Se and B decreased from 1.52
      +/- 0.55 to 0.84 +/- 0.21 l min-1 kPa-1, and from 4.0 +/- 0.5 to 3.0 +/- 0.6 kPa,
      respectively, not significantly different from the changes encountered in the
      denervated animals. 5. It is argued that the effect of acetazolamide on the CO2
      sensitivity of the peripheral chemoreflex loop in intact cats may be caused by a
      direct effect on the carotid bodies. Both in intact and in denervated animals the
      effects of the drug on Sc and B may not be due to a direct action on the central
      nervous system, but rather to an effect on cerebral vessels resulting in an
      altered relationship between brain blood flow and brain tissue PCO2.

PMID- 8866366
TI  - Rostrocaudal gradient of mechanical advantage in the parasternal intercostal
      muscles of the dog.
AB  - 1. Previous theoretical studies have led to the predictions that, in the dog, the
      parasternal intercostal muscles in the rostral interspaces shorten more during
      passive inflation than those in the caudal interspaces and have, therefore, a
      greater inspiratory mechanical advantage. The present studies were undertaken to
      test these predictions. 2. The effects of passive inflation on the length of the
      parasternal intercostals interspaces 1 to 7 were evaluated with markers implanted
      in the costal cartilages. Although the muscles in all interspaces shortened with
      passive inflation, the fractional shortening increased from the first to the
      second and third interspaces and then decreased continuously to the seventh
      interspace. 3. To understand this peculiar distribution, a geometric model of the
      parasternal area was then developed and a relation was obtained between muscle
      shortening and the angles that describe the orientation of the muscle and costal
      cartilage relative to the sternum. Measurement of these angles indicated that the
      rostrocaudal gradient of parasternal shortening resulted from the different
      orientations of the costal cartilages and their different rotations during
      passive inflation. 4. The changes in airway pressure generated by the parasternal
      intercostals in interspaces 3, 5 and 7 were finally measured during selective,
      maximal stimulation. The fall in pressure was invariably greatest during
      contraction of the third interspace and smallest during contraction of the
      seventh. 5. These observations indicate that, in the dog, the rostrocaudal
      gradient in rib rotation induces a rostrocaudal gradient of mechanical advantage
      in the parasternal intercostals, which has its climax in the second and third
      interspaces. These observations also support the concept that the respiratory
      effect of a given respiratory muscle can be computed from its behaviour during
      passive inflation.

PMID- 8866367
TI  - Rostrocaudal gradient of electrical activation in the parasternal intercostal
      muscles of the dog.
AB  - 1. Because the inspiratory mechanical advantage of the canine parasternal
      intercostal muscles is greatest in the third interspace and decreases gradually
      in the caudal direction, the electromyograms of these muscles in interspaces 3, 5
      and 7 have been recorded in anaesthetized, spontaneously breathing dogs. Each
      activity was expressed as a percentage of the activity measured during tetanic,
      supramaximal stimulation of the internal intercostal nerve (maximal activity). 2.
      Parasternal inspiratory activity during resting, room air breathing was
      invariably greater in the third than in the fifth interspace (62.0 +/- 6.0 vs.
      41.3 +/- 4.6% of maximal activity; P < 0.001) and smallest in the seventh
      interspace (22.8 +/- 2.7% of maximal activity; P < 0.001). This distribution of
      activity persisted during hyperoxic hypercapnia and during breathing against
      increased inspiratory airflow resistance. 3. This rostrocaudal distribution of
      activity also persisted after complete paralysis of the diaphragm as well as
      after deafferentation of the ribcage. 4. Studies of the distribution of the
      muscle fibre types indicated that the parasternal intercostals in all interspaces
      had a higher proportion of slow-twitch oxidative (SO; type I) fibres than fast
      twitch oxidative-glycolytic (FOG; type II a) fibres. 5. Thus the topographic
      distribution of parasternal inspiratory activity along the rostrocaudal axis of
      the ribcage is precisely matched with the topographic distribution of mechanical
      advantage. This extraordinarily effective pattern of activation probably results
      from the unequal distribution of central inputs throughout the parasternal
      motoneurone pool.

PMID- 8866368
TI  - Central effects of 5-HT on activity of respiratory and hypoglossally innervated
      muscles in newborn kittens.
AB  - 1. In decerebrate kittens (n = 29), electrical activity was studied in the 3rd
      intercartilaginous (inspiratory), the 9th internal intercostal (expiratory) and
      the hypoglossally innervated muscles (geniohyoid m. and sternohyoid m.) evoked by
      the application of 5-HT (n = 16) or related agents (5-HT1A agonist, 8-OH-DPAT (n
      = 6) and 5-HT2 agonist, DOI floor of the IVth ventricle. 2. The application of a
      control solution (n = 2) produced no significant changes either in minute
      inspiratory frequency (Fi) or in the electrical activity of the muscles studied.
      Except for these controls, only one trial with one dose of one drug was performed
      in a given kitten. 3. A dose-related decrease in Fi was observed in response to 5
      HT. Low doses (50-500 nmol, n1 = 8) induced a long-lasting bradypnoea; high doses
      (5000-10,000 nmol, n2 = 8) induced prolonged periods of apnoea. 4. The apnoeas
      observed in tracheotomized (n = 3) or non-tracheotomized (n2 = 8) kittens were
      mainly of central origin and linked to the lengthening of expiratory time. The
      expiratory muscle activation came on with the reinforcement of the activity of
      hypoglossally innervated muscles. 5. Application of agonists showed that both the
      5-HT-dependent modulation of Fi and the effects of 5-HT on the activity of the
      muscles studied resulted predominantly from activation of 5-HT2 receptors.

PMID- 8866369
TI  - Neuropeptide Y-like substances are released from the rostral brainstem of cats
      during the muscle pressor response.
AB  - 1. In this study, the release of immunoreactive neuropeptide Y (NPY)-like
      substances (irNPYs) was measured from the rostral brainstem in response to
      fatiguing isometric contractions of the hindlimb muscle of cats anaesthetized
      with alpha-chloralose. 2. The irNPYs were measured using a solid phase
      autoradiographic immunoassay. NPY antibody-coated glass microelectrodes were
      inserted stereotaxically into the rostral brainstem during rest and contractions.
      Control procedures such as passive leg flexing, stimulation of the central end of
      the cut tibial nerve, brief repeated carotid occlusions and carotid sinus nerve
      stimulations were performed to determine whether patterns of release of irNPYs
      were specific to the pathways activated during the muscle pressor response. 3.
      During isometric contractions, the mean arterial blood pressure (MABP) and heart
      rate (HR) increased by 60-70 mmHg and 15-20 beats min-1, respectively. Only the
      brief carotid occlusions caused a similar increase in MABP and HR. 4. During
      isometric contractions, less irNPYs were released from sites in the lateral
      reticular nucleus, lateral tegmental field and vestibular nuclei at a level in
      the brainstem 4.0-4.4 mm rostral to the obex. In contrast, irNPYs were released
      from sites near the lateral tegmental field and nucleus ambiguus at a more caudal
      level tested (1.3 mm anterior to the obex) in response to contractions. Brief
      carotid occlusions caused a release of irNPYs from the lateral reticular nucleus
      on the contralateral side of the brainstem (at 3.5 mm anterior to the obex). None
      of the other procedures resulted in a release of irNPYs from these sites in the
      brainstem. 5. These data indicate there are differences in the patterns of
      release of irNPYs in response to activation of reflex pathways which increase
      arterial pressure. Given the sites in the rostral brainstem where irNPYs were
      released, irNPYs may be involved with the central regulation of arterial pressure
      during the muscle pressor response.

PMID- 8866370
TI  - Impaired sympathetic vascular regulation in humans after acute dynamic exercise.
AB  - 1. The reduction in vascular resistance which accompanies acute dynamic exercise
      does not subside immediately during recovery, resulting in a post-exercise
      hypotension. This sustained vasodilatation suggests that sympathetic vascular
      regulation is altered after exercise. 2. Therefore, we assessed the baroreflex
      control of sympathetic outflow in response to arterial pressure changes, and
      transduction of sympathetic activity into vascular resistance during a sympatho
      excitatory stimulus (isometric handgrip exercise) after either exercise (60 min
      cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated
      rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and
      calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/-
      9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and
      sympathetic outflow was shifted downward after exercise (post-exercise intercept,
      218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/-
      51 total integrated activity (heartbeat)-1, P < 0.05), indicating less
      sympathetic outflow across all diastolic pressures. Further, the relation between
      sympathetic activity and vascular resistance was attenuated after exercise (post
      exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post
      sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05),
      indicating less vasoconstriction with any increase in sympathetic activity. 4.
      Thus, both baroreflex control of sympathetic outflow and the transduction of
      sympathetic activity into vascular resistance are altered after dynamic exercise.
      We conclude that the vasodilation which underlies post-exercise hypotension
      results from both neural and vascular phenomena.

PMID- 8866372
TI  - Successful revascularization of a toe-avulsion injury in a three-year-old child,
      using a digital artery transfer.
AB  - The partially avulsed second toe of a 3-year-old girl was successfully
      revascularized using a digital artery transfer from the adjacent third toe. The
      technique is explained and discussed.

PMID- 8866371
TI  - Phase-shifting human circadian rhythms: influence of sleep timing, social contact
      and light exposure.
AB  - 1. Both the timing of behavioural events (activity, sleep and social
      interactions) and the environmental light-dark cycle have been reported to
      contribute to entrainment of human circadian rhythms to the 24 h day. Yet, the
      relative contribution of those putative behavioural synchronizers to that of
      light exposure remains unclear. 2. To investigate this, we inverted the schedule
      of rest, sedentary activity and social contact of thirty-two young men either
      with or without exposure to bright light. 3. On this inverted schedule, the
      endogenous component of the core temperature rhythm of subjects who were exposed
      to bright light showed a significant phase shift, demonstrating that they were
      adapting to the new schedule. In contrast, the core temperature rhythm of
      subjects who were not exposed to bright light moved on average 0.2 h later per
      day and after 10 days had not significantly adapted to the new schedule. 4. The
      direction of phase shift in the groups exposed to bright light was dependent on
      the time of bright light exposure, while control subjects drifted to a later hour
      regardless of the timing of their schedule of sleep timing, social contact and
      meals. 5. These results support the concept that the light-dark cycle is the most
      important synchronizer of the human circadian system. They suggest that inversion
      of the sleep-wake, rest-activity and social contact cycles provides relatively
      minimal drive for resetting the human circadian pacemaker. 6. These data indicate
      that interventions designed to phase shift human circadian rhythms for adjustment
      to time zone changes or altered work schedules should focus on properly timed
      light exposure.

PMID- 8866373
TI  - Cutaneous blood-flow patterns in free flaps determined by laser Doppler
      flowmetry.
AB  - Accurate monitoring of tissue perfusion in microvascular surgery is paramount to
      flap survival. Many methods have been proposed for monitoring of flaps, but none
      have achieved widespread acceptance. The laser Doppler has been shown to be
      beneficial in monitoring flap perfusion. Trends have been noted in laser Doppler
      measurements over time in free TRAM, free latissimus dorsi, and free iliac-crest
      osteomyocutaneous flaps. TRAM flaps demonstrated a slow increase in the laser
      Doppler index (LDI), with a peak increase in skin blood flow of over 600 percent
      at 52 to 80 hr postoperatively (LDI 6.77 +/- 3.51), and then a gradual decline to
      previous baseline. Latissimus dorsi flaps also demonstrated a slow increase until
      about 80 hr postoperatively (LDI 9.8 +/- 10.65), indicating an increase in skin
      blood flow of almost 900 percent. Iliac-crest osteomyocutaneous free flaps had a
      slow increase in blood flow until approximately 70 hr postoperatively, when the
      LDI (5.5) increased, representing an increase in skin blood flow of over 500
      percent. These changes in skin blood flow over time, seen with continuous laser
      Doppler measurements, depict the dynamic nature of skin blood flow and allow
      predictive patterns to be established, instead of single normal values, by which
      to gauge adequate flap perfusion.

PMID- 8866374
TI  - The internal topography of the axillary nerve: an anatomic and histologic study
      as it relates to microsurgery.
AB  - The topography of the fascicular groups of the axillary nerve throughout its
      course from the posterior cord until its passage through the quadrangular space
      was studied in dissections of 40 brachial plexuses under x3.5 loupe
      magnification. Additionally, 10 axillary nerves were excised in toto, and
      histologic serial sections were done to define fascicular arrangement. In all
      specimens, the motor fascicular group for the deltoid muscle was located most
      superiorly at the level of the quadrangular space. This motor portion could be
      identified as a distinct entity, up to 45 mm proximal to this level. In surgical
      treatment of axillary nerve repair, one should direct special attention to the
      correct identification, matching, and alignment of this motor fascicle, to avoid
      wasteful regeneration of axons into the functionally unrelated fascicles to the
      teres minor and the lateral shoulder skin.

PMID- 8866375
TI  - Combination therapy for salvaging a failing, experimental skin flap.
AB  - The failing free flap remains a major problem for the reconstructive surgeon.
      Many and varied pharmacologic agents have been utilized to reverse the effects of
      ischemia in these flaps. Treatments have been aimed at inhibiting presumed
      causative factors in the no-reflow phenomenon. Therapy has generally been single
      in nature and designed to affect only one of these presumed factors. In this
      study, several pharmacologic agents were utilized individually or in combination
      therapy as postischemic washouts, in an effort to attack the multiple causative
      factors in the no-reflow phenomenon and to improve flap survival in a rat
      abdominal skin flap model. The treatment agents included lactated Ringer's,
      superoxide dismutase, and urokinase, with each used independently as a
      postischemic perfusion washout. Combination therapy utilized an initial
      postischemic perfusion with urokinase, followed by a second perfusion washout
      with superoxide dismutase. After 18 hr of primary ischemia, there was increased
      flap survival in the animals undergoing perfusion washout with either superoxide
      dismutase alone or with combined urokinase and superoxide dismutase washouts,
      compared to all other treatments (p < 0.001). It was found that flaps undergoing
      combined urokinase and superoxide dismutase postischemic perfusion washouts
      demonstrated significantly improved survival after 20 hr of primary ischemia,
      compared to all other therapies (p < 0.05). By demonstrating improved survival
      when a thrombolytic agent is used in conjunction with an oxygen free radical
      scavenger, these findings may have implications in the treatment of clinically
      failing free flaps.

PMID- 8866376
TI  - A simple method of free-flap monitoring using a superficial vein.
AB  - A new, simple method for flap monitoring is presented. Dissecting a superficial
      flap vein, which is closed by an Acland clamp, and opening the clamp shortly
      thereafter, allows objective, postoperative flap monitoring. The surgical
      technique, advantages, and possible difficulties of the procedure are discussed.

PMID- 8866377
TI  - A histomorphometric analysis of the cross-facial nerve graft in the treatment of
      facial paralysis.
AB  - One of the most unsettling sequela of facial paralysis (FP) is the loss of the
      blink reflex, leading to both a functional and aesthetic deformity. A successful
      method of treating FP and, in particular, loss of eye-sphincter function, is the
      use of the cross-facial nerve graft (CFNG) to reinnervate the previously
      denervated orbicularis oculi muscle. The present study examined the
      histomorphometric aspects of the entire CFNG, with respect to axon diameter and
      myelin area. The axon profile of the CFNG had a positive correlation with motor
      end-plate counts and electrophysiologic recordings. These results should help in
      further understanding the number of motor axons needed to restore adequate
      function to the paralyzed eye sphincter, and establish more rational
      reconstructive procedures.

PMID- 8866378
TI  - Protection against ischemic-reperfusion injury of skeletal muscle: role of
      ischemic preconditioning and adenosine pretreatment.
AB  - Prolonged tissue ischemia and subsequent reperfusion result in significant tissue
      injury due to the ischemic-reperfusion syndrome. Although skeletal muscle has
      significant tolerance to ischemic-reperfusion injury (IRI), compared to other
      organ systems, IRI of skeletal muscle does occur when there is a prolonged
      ischemic period. In many reconstructive surgical procedures involving
      microsurgery and prolonged tissue ischemia time, IRI-induced skeletal-muscle
      injury is a serious clinical concern. Specifically, there are significant
      vascular complications (venous thrombosis and arteriolar no-reflow) and loss of
      transplanted muscle function on reperfusion with prolonged ischemia. Ischemic
      preconditioning (IPC) or adenosine (ADO) pretreatment applied prior to the
      ischemic period are known to protect against IRI in cardiac muscle. Recent data
      from basic science research suggest that IPC or ADO pretreatment may be employed
      to protect skeletal muscle against IRI. This review summarizes the basic
      mechanisms and potential clinical relevance of ischemia- and reperfusion-induced
      skeletal muscle injury and describes how skeletal muscle can be protected against
      IRI with IPC or ADO pretreatment.

PMID- 8866380
TI  - Laparoscopically assisted colpotomy with the Pelosi illuminator and Visiport
      trocar system.
AB  - OBJECTIVE: To describe a technique for laparoscopically assisted colpotomy. STUDY
      DESIGN: The Pelosi endoscopic illuminator and Visiport trocar system were
      combined to perform visually guided transvaginal colpotomy. Thirty-five
      consecutive laparoscopic gynecologic cases necessitating cul-de-sac entry were
      approached with this technique. RESULTS: The technique was performed successfully
      in all 35 cases without complications or technical difficulties and with an
      average colpotomy time of 3.5 minutes. Indications for colpotomy included removal
      of laparoscopic supracervical hysterectomy specimens, myomata, large adnexal
      cysts and large tubal pregnancy. CONCLUSION: This colpotomy technique is quick,
      efficient and easy to perform. Advantages include retention of pneumoperitoneum,
      facilitated transvaginal insertion of instrumentation to remove pelvic masses,
      avoidance of an electrosurgical or laser incision, and complete visual control,
      which minimizes the possibility of traumatic injury to bowel and other pelvic
      structures.

PMID- 8866379
TI  - Use of endometrial measurement as an exclusion criterion for in vitro
      fertilization using clomiphene citrate.
AB  - OBJECTIVE: Previous reports have indicated an association between endometrial
      development and pregnancy outcome for patients treated with clomiphene citrate
      (CC) in conjunction with intrauterine insemination or intercourse. We expanded
      the use of CC for ovulation induction in association with in vitro fertilization
      (IVF). This study was designed to determine if endometrial thickness should be
      used as an inclusion or exclusion criterion for CC-IVF. STUDY DESIGN: One hundred
      twenty-eight patients were enrolled in an ovulation-induction regimen using CC
      for expected IVF-ET between January 1992 and December 1992. A total of 81
      patients met inclusion criteria for CC-IVF and had endometrial measurement
      performed prior to human chorionic gonadotropin administration. Patients were
      categorized on the basis of endometrial measurement as follows: (A) > 4 - < 7 mm,
      (B) > or = 7 - < or = 10 mm, and (C) > 10 mm. Standard IVF was performed, and
      pregnancy rates for each category were evaluated. RESULTS: A total of 23
      pregnancies (28% per retrieval) were established. Pregnancy rates were not
      different by category (P > .10, Fisher's Exact Test): (A) 3/15 (20%), (B) 13/41
      (32%), and (C) 7/25 (28%). CONCLUSION: These data suggest that for CC-IVF.
      endometrial measurement should not be used as an exclusion criterion since
      pregnancies occurred at comparable frequencies in all the groups.

PMID- 8866381
TI  - Human endometrial cells cultured in a type I collagen gel.
AB  - OBJECTIVE: To elaborate in vitro conditions that enable epithelial and stromal
      cells of human endometrium to grow within a gel of collagen. STUDY DESIGN:
      Primary cultures of epithelial cells derived from human endometrial biopsies were
      dissociated and mixed with a collagen solution, and the gel was allowed to form
      at physiologic pH. Control cultures were grown in plastic dishes. DNA replication
      was assessed by 3H-thymidine incorporation, morphology by histology and cell
      characterization by monoclonal antibodies to cytokeratins. RESULTS: Cells grown
      on plastic dishes exhibited a typical monolayer arrangement, and replication was
      increased 1.6-fold by the addition of stromal cell-conditioned medium (50%
      vol/vol). After a two- to three-week period of culture within the collagen gel in
      the presence of either stromal cells or stromal cell-conditioned medium,
      epithelial cells formed circular arrangements of cuboidal to columnar cells with
      open lumina resembling glands. These glandlike structures were cytokeratin
      positive as assessed by immunohistochemistry, thereby confirming their epithelial
      nature. CONCLUSION: The development of differentiated epithelial structures in a
      three-dimensional gel provides a promising method of studying various biochemical
      and cellular interactions of eutopic and ectopic endometrium.

PMID- 8866382
TI  - Natural killer cell function in women with vestibulitis.
AB  - OBJECTIVE: To assess natural killer (NK) cell activity in patients with
      vestibulitis. STUDY DESIGN: Twenty-two patients who met the International Society
      for the Study of Vulvar Disease criteria for vestibulitis and 17 age-, sex- and
      race-matched controls were recruited. NK cell activity was examined using a
      standard, four-hour 51Cr-release assay, freshly and after stimulation with
      interleukin 2 (IL2) or alpha interferon (IFN alpha). RESULTS: The subject samples
      had significantly decreased fresh NK cell activity (mean lytic units [LU]/10(6)
      peripheral blood leukocytes [PBLs] of 0.93 vs. 4.19, P < .001). This activity was
      augmented in response to either IFN or IL2. However, it remained significantly
      lower than in the control samples (12.07 vs. 20.6 LU/10(6) PBL, P = .007 for IL2
      and 5.98 vs. 15.33 LU/10(6) PBL, P < .001 for IFN). This difference was not
      universal since the major histocompatibility-nonrestricted T killer cell activity
      of the subject samples was not significantly different from that in the control
      samples. CONCLUSION: This pilot study suggests that patients with vulvar
      vestibulitis have markedly decreased NK cell activity. Although this activity is
      increased in response to IL2 or IFN, it remains significantly impaired in
      comparison to the control samples.

PMID- 8866383
TI  - Vulvovaginal hematomas complicating delivery. Rationale for drainage of the
      hematoma cavity.
AB  - OBJECTIVE: To review the management of puerperal vulvovaginal hematomas and
      report on the use of closed system drainage in cases in which operative
      intervention was used. STUDY DESIGN: A retrospective review of medical records
      for a five-year period was conducted. The charts of all patients in whom
      puerperal vulvovaginal hematomas occurred were reviewed and data extracted
      regarding possible etiologic factors, details of delivery, characterization of
      the hematoma, surgical intervention and type of drain used. Also recorded was
      length of stay and postoperative complications. RESULTS: Eleven patients with
      hematomas were identified, for an incidence of 1/526. All patients received
      antibiotics; transfusion was required in eight patients. Drains were used in nine
      patients: Penrose in four and closed system drainage in five. All drains were
      brought through a separate site distant from the repair. There was one
      postoperative abscess, which resolved with wound care, resulting in no long-term
      morbidity. CONCLUSION: Puerperal vulvovaginal hematomas may be a life-threatening
      event. Review of the literature and our experience suggests that aggressive
      operative management and the use of drains are beneficial in the management of
      these patients. Closed system drainage may be an effective adjunct in the
      management of vulvovaginal hematomas.

PMID- 8866384
TI  - Ampicillin/sulbactam vs. clindamycin/gentamicin in the treatment of postpartum
      endometritis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of ampicillin/sulbactam with those
      of clindamycin/gentamicin. STUDY DESIGN: A prospective, randomized clinical trial
      of patients with the diagnosis of postpartum endometritis. Intravenous
      ampicillin, 2.0 g, combined with 1.0 g sulbactam was administered every six hours
      or intravenous clindamycin, 900 mg, plus gentamicin, 1.5 mg/kg (not to exceed 150
      mg unless gentamicin levels were obtained) every eight hours. Endometrial and
      blood specimens were obtained for culture and antibiotic susceptibility testing.
      RESULTS: One hundred twenty-nine hospitalized women with the diagnosis of
      endometritis were enrolled. Both treatment regimens were equally effective. At
      the end of treatment, 42 of 51 (82%) ampicillin/sulbactam-treated patients
      achieved clinical cure in comparison to 47 of 56 (84%) patients in the
      clindamycin/gentamicin group. Respective bacterial eradication rates of 86% and
      84% for each treatment group were seen. Both antibiotic regimens were well
      tolerated, with no statistically significant difference in the incidence of
      adverse experiences. CONCLUSION: The two antibiotic regimens were equally
      effective for a clinical cure, bacterial eradication and incidence of adverse
      experiences.

PMID- 8866385
TI  - Blood pressure monitoring during pregnancy. Accuracy of portable devices designed
      for obese patients.
AB  - OBJECTIVE: To compare the accuracy of three commercially available blood pressure
      monitoring devices having cuffs placed at different anatomic sites on obese
      pregnant women with large arms. STUDY DESIGN: Fifty-five obese pregnant women
      (body mass index > 27.3) were eligible for participation; each had an upper arm
      circumferences > 35 cm. The three different portable devices compared had cuffs
      that fit easily around either the index finger, wrist or large arm. Two
      recordings using each device were compared with those obtained simultaneously
      using a well calibrated monitor. RESULTS: Systolic, diastolic and mean arterial
      pressure recordings did not correlate between the monitor and devices with the
      cuff around the finger (r2 = .17, .17, .22), wrist (.30, .24, .33) or large arm
      (.44, .26, .40). The percentages of measurement differences within 5 mm Hg for
      the systolic, diastolic and mean arterial pressure were low for the device with
      the cuff around the finger (11.0%, 25.5%, 23.6%), wrist (33.0%, 46.4%, 35.5%) or
      large arm (38.5%, 29.4%, 46.7%). CONCLUSION: Despite their commercial appeal,
      none of these portable blood pressure monitoring devices was accurate for use by
      obese pregnant patients with large arms.

PMID- 8866386
TI  - Squamous intraepithelial cervical lesions in human immunodeficiency virus
      seropositive women.
AB  - OBJECTIVE: To evaluate the relationship between human immunodeficiency virus
      (HIV) infection, CD4 serum level, cervical squamous intraepithelial lesions
      (SILs) and risk factors for human papillomavirus (HPV)-related dysplasia in HIV
      positive women. STUDY DESIGN: All 51 eligible patients who were seen at the
      Colposcopic Outpatient Service, Aviano Cancer Center, Aviano, Italy, from July 1,
      1993, to June 30, 1994, were studied for risk factors for HPV and HIV infection
      and had cervical cytologic smears, colposcopy with cervical biopsy and a serum
      CD4 count. RESULTS: Thirty of 51 patients (59%) had cytohistologically confirmed
      SIL. The prevalence of SIL was higher in HIV Centers for Disease Control stage IV
      disease than stages II and III (22/29 vs. 8/22 P < .05). There was no significant
      difference in the CD4 count between women with or without SIL (321 +/- 310 vs.
      401 +/- 295/mm3 [mean +/- SD]). No relationship was found between CD4 count and
      severity of SIL (low grade SIL, 210 +/- 203/mm3; high grade SIL, 580 +/-
      357/mm3). CONCLUSION: In our series there was no relationship between CD4 count
      and cervical SIL, suggesting that the expression of HPV-related dysplasia is a
      complex process in which risk factors for genital SIL play an important role,
      while the role of HIV must be defined again.

PMID- 8866387
TI  - Predictors of persistent disease in women with complete hydatidiform mole.
AB  - OBJECTIVE: To determine the most significant factors for persistent disease in
      women with hydatidiform mole. STUDY DESIGN: Eighty-two patients who were managed
      consecutively without prophylactic chemotherapy between 1973 and 1993 were
      analyzed retrospectively for clinical and pathologic features, including age of
      the patient, size of the uterus, human chorionic gonadotropin (hCG) level,
      presence of theca lutein cysts, evidence of preeclampsia or hyperthyroidism,
      history of hydatidiform moles, trophoblastic hyperplasia, nuclear atypia,
      necrosis and hemorrhage, trophoblastic maturation, presence of fibrinoid layer
      and ratio of cytotrophoblast to syncytial trophoblast. RESULTS: Thirty-one
      patients developed persistent trophoblastic neoplasia (38%). Of the parameters
      evaluated, elevated hCG level, advanced age, history of hydatidiform mole,
      presence of hyperplasia, marked nuclear atypia and necrosis, and hemorrhage were
      significant risk factors for persistent neoplasia after univariate analysis.
      Among the factors analyzed, trophoblastic hyperplasia (relative ration [RR] =
      3.56), age (RR = 2.87) and history of mole (RR = 2.57) were identified as the
      most powerful indicators of persistent disease after multivariate analysis.
      CONCLUSION: Evaluation of the clinical and pathologic features, such as age,
      history of mole and presence of trophoblastic proliferation may aid in defining a
      subset of patients at high risk for persistent disease, who require closer follow
      up and administration of prophylactic chemotherapy.

PMID- 8866388
TI  - Prevention of preterm birth. Role of daily telephone contact.
AB  - OBJECTIVE: To compare the effectiveness of routine management of patients at high
      risk for preterm delivery to the effectiveness of routine management in
      combination with daily telephone nursing contact. STUDY DESIGN: The control
      group, 1 (n = 21), had education and frequent prenatal visits and cervical
      examinations. The study group, 2 (n = 21), had education, frequent prenatal
      visits and cervical examination, and daily telephone contact. Group 3 (n = 22)
      received education but refused to participate. RESULTS: There were no significant
      differences (SD) between groups in race, smoking, age, multiple gestation,
      visits, diagnosis of premature labor, mean days gained after diagnosis of
      premature labor, tocolytic use or bed rest. There was also no SD in preterm birth
      rate, mode of delivery, number of maternal or neonatal hospital days, mean
      neonatal weight or gestational age at delivery between groups. While not reducing
      the overall incidence of preterm birth, this management for all groups resulted
      in a more advanced gestational age at the time of delivery (mean change = 7.5
      weeks, P < .0001) when compared to the patient's first preterm birth. CONCLUSION:
      This study indicated that daily contact, while providing reassurance and support,
      did not change the outcome when the study group was compared to women managed
      similarly but without daily contact.

PMID- 8866389
TI  - Operative laparoscopy for the treatment of ectopic pregnancy in a residency
      program.
AB  - OBJECTIVE: To compare the effectiveness and safety of operative laparoscopy (OL)
      when used for the treatment of ectopic pregnancy in the setting of a residency
      training program. STUDY DESIGN: We retrospectively reviewed records of all
      patients with diagnostic laparoscopy documenting the presence of an ectopic
      pregnancy. Patients who met the following criteria were selected: hemodynamic
      stability, tubal distortion no greater than 5 cm and adequate visualization of
      the pelvis. The cases performed via OL were compared to the cases performed via
      laparotomy (LAP). All the surgery had been performed by resident physicians with
      the attending gynecologist as first assistant/supervisor. RESULTS: Ninety-five
      cases performed from March 1989 to April 1992 met the above criteria. Group 1
      consisted of 61 patients treated with LAP. Group 2 consisted of 34 patients
      treated with OL. The operating time (76.8 +/- 19.0 vs 76.0 +/- 23.0 min, mean +/-
      SD) and the estimated blood loss (275.0 +/- 183.7 vs. 70.5 +/- 75.2 ml) were
      similar for both groups. The hospital stay for the LAP group was longer than for
      the OL group (3.7 +/- 1.2 vs. 1.4 +/- 0.6 days, P < .001). The surgical
      complication rate was also higher in the LAP group (23% vs 2.9%, P = .16).
      CONCLUSION: In our residency program the introduction of OL for the management of
      ectopic pregnancy has resulted in shorter hospital stays and lower morbidity
      without increased duration of the surgical episode or increased blood loss.

PMID- 8866390
TI  - Effect of MgSO4 on heart rate monitoring in the preterm fetus.
AB  - OBJECTIVE: To evaluate in a controlled, blind fashion, using both subjective and
      objective criteria, whether MgSO4 is associated with clinically significant
      changes in fetal heart rate monitoring. STUDY DESIGN: Fetal heart rate tracings
      were prospectively collected before and after MgSO4 loading in 50 preterm labor
      patients. Three obstetricians, blind to treatment status, graded the tracings
      using both subjective and objective criteria. RESULTS: The baseline fetal heart
      rate declined slightly after therapy. Subjective, but not objective, evaluation
      demonstrated a greater likelihood of decreased variability after MgSO4 loading.
      There was no difference in periodic changes after MgSO4 loading. Multiple
      regression analysis showed a greater likelihood of decreased variability at
      earlier gestational ages but no relationship to the serum magnesium level.
      CONCLUSION: Magnesium sulfate tocolysis is associated with a subjective decrease
      in fetal heart rate variability in the preterm fetus.

PMID- 8866391
TI  - Pregnancy after failed tubal sterilization.
AB  - OBJECTIVE: To review the pregnancy outcome in patients with failed tubal
      sterilization treated in our hospital and to compare the incidence of ectopic
      pregnancy in our study group with the experience at other military hospitals and
      with the incidence of ectopic pregnancy in similar patients reported in the
      literature. STUDY DESIGN: A registry of failed tubal sterilization was started at
      our hospital in 1989. We entered all information regarding the type of procedure
      and pregnancy outcome as the patients presented for care. Information on the
      experience at other military hospitals was obtained through review of data
      provided by the epidemiology section of the Health Services Command, San Antonio,
      Texas. RESULTS: From 1989 to 1991, 12 patients with failed tubal sterilization
      received care at our hospital. Eight patients (67%) had ectopic pregnancies. Of
      137 patients identified through the Health Services Command, 49 (36%) had ectopic
      pregnancies. CONCLUSION: The literature reports a 5-90% incidence of ectopic
      pregnancy after failed tubal sterilization. The data from our registry and from
      the Health Services Command corroborate the increased likelihood of ectopic
      pregnancy in patients with failed tubal sterilization and underscore the need for
      close follow-up of these patients until the location of the pregnancy is
      documented.

PMID- 8866392
TI  - Superovulation and intrauterine insemination vs. superovulation alone in the
      treatment of unexplained infertility. A randomized study.
AB  - OBJECTIVE: To assess whether intrauterine insemination (IUI) improves the
      fertility rates in women with unexplained infertility. STUDY DESIGN: We recruited
      68 women with unexplained infertility and allocated them randomly to treatment
      with three to five cycles of superovulation plus IUI (36 patients) or
      superovulation alone (32 patients). Superovulation was obtained with clomiphene
      citrate, human menopausal gonadotropins and human chorionic gonadotropins.
      RESULTS: The cycle fecundity rate was 10% in patients who underwent
      superovulation alone and 19% in those treated with superovulation plus IUI (P <
      .05). CONCLUSION: Our results demonstrate that superovulation plus IUI is more
      effective than superovulation alone in the treatment of unexplained infertility.

PMID- 8866393
TI  - Giant cervical polyp. A case report.
AB  - BACKGROUND: Very large cervical polyps are rarely reported. CASE: A giant
      cervical polyp, 17 x 10 x 5 cm, protruded through the vaginal introitus in a 27
      year-old, sexually inactive woman. CONCLUSION: Although carcinomatous change
      occurs in 1.7% of cervical polyps, malignant degeneration did not occur in the
      six reported cases. Thus, biopsy of these tumors before excision may not be
      necessary.

PMID- 8866394
TI  - Creating a virtual materials and resources index for health education using the
      World Wide Web.
AB  - The Internet represents the principal system for distributing information
      worldwide, offering health educators a powerful communications medium. This
      article describes an assignment that teaches students how to use the World Wide
      Web (WWW). The first part provides an overview of the Internet, its principal
      services. browser software, and Netscape Navigator. The second part describes the
      assignment, complete with instructional objectives, computer facilities used to
      implement the strategy, and a summary of classroom and laboratory activities. The
      third part describes procedures for teaching students how to use the WWW.
      Students learn how to explore the WWW and to develop a customized virtual
      directory of health materials and resources using Netscape Navigator Bookmark
      tools. Recommendations on how the approach can be modified are offered.

PMID- 8866395
TI  - Pro-innovation bias: the case of the Giant Texas SmokeScream.
AB  - A common approach to promoting improvements in school health instruction involves
      development and dissemination of new curricula and teaching materials.
      Ironically, potential effects of innovative materials on student outcomes and
      actual teacher instructional practices rarely are considered important in
      decisions concerning use of new material. This study examined the impact of a new
      curricular innovation, the Giant Texas SmokeScream (GTSS), on 512 middle grade
      students' knowledge, perceptions, and behavioral intent about smoking. The data
      provided a basis for discussion of what Rogers labeled "pro-innovation bias."
      Data indicated the program had no effect on students. The GTSS program itself,
      although popular with schools, was questioned as being atheoretical in its
      approach to health education and ineffective in its outcomes. These data
      illustrate the need for programs to be based on sound theory and evaluated
      rigorously prior to general adoption. Additionally, program evaluations focused
      solely on student effects are insufficient in their assessment of adoption and
      implementation practices.

PMID- 8866396
TI  - Student victimization at school.

PMID- 8866397
TI  - Tobacco use and usual source of cigarettes among high school students--United
      States, 1995.

PMID- 8866398
TI  - Plotting on the food pyramid: an evaluation of dietary patterns.
AB  - From this lesson, students will discover deficiencies in their eating patterns
      that they may be unaware of otherwise. Consequently, they also will confirm those
      habits that contribute to a balanced diet. By creating goals and objectives,
      students will outline desired changes and delineate concrete steps in which to
      achieve those changes.

PMID- 8866399
TI  - Inside-out signaling through integrins.
AB  - Rapid and yet precisely controlled changes in cell adhesion are a hallmark of a
      number of basic physiological processes. Many of these processes directly impact
      upon nephrology, including: (1) cell migration, which occurs during leukocyte
      infiltration into inflammatory sites (e.g., in glomerulonephritis, interstitial
      nephritis, and renal transplant rejection) and during embryogenesis (e.g., in
      development of the genitourinary system): and (2) platelet aggregation at sites
      of clot formation (e.g., in glomerulonephritis). The integrins are a family of
      adhesion molecules whose function is controlled by the cells that express them,
      and this properly makes them eminently suitable receptors for those situations
      that demand flexibility of the cellular adhesive phenotype. The control of
      integrin function occurs via regulatory signals that originate within the cell
      cytoplasm and are then transmitted to the external ligand-binding domain of the
      receptor. The generation and transmission of these "inside-out" signals are the
      subjects of intensive research that will be summarized in this review article.

PMID- 8866400
TI  - Growth factors and apoptosis in neonatal ureteral obstruction.
AB  - Renal insufficiency as a result of congenital obstructive nephropathy is a
      consequence of impaired renal growth: chronic unilateral ureteral obstruction
      (UUO) results in greater injury to the immature kidney than to the adult kidney.
      The neonatal kidney responds to UUO by marked activation of the renin-angiotensin
      system, which contributes to severe vasoconstriction and progressive interstitial
      fibrosis of the obstructed kidney. The latter results in part because of
      activation of transforming growth factor-beta 1 by angiotensin II. Chronic UUO in
      the neonatal rat delays maturation of the obstructed kidney, possibly in part
      through suppressed expression of epidermal growth factor. In addition to
      affecting growth factors, UUO stimulates apoptosis in the obstructed kidney,
      which is quantitatively greater in the neonate than in the adult. In contrast,
      expression of clusterin, a glycoprotein that may play a protective role in the
      response to UUO, is greater in the adult than in the neonatal obstructed kidney.
      The response of the developing kidney to UUO is similar in a number of respects
      to cystic kidney disease. This includes a reduction in epidermal growth factor,
      and increased apoptosis that may result from suppression of bcl-2, an oncoprotein
      that inhibits apoptosis. Improved knowledge of the cellular and molecular basis
      for cystic renal disorders should lead to specific intervention in fetuses and
      infants with congenital obstructive nephropathy, thereby improving renal growth
      and development.

PMID- 8866401
TI  - Aging and the kidney.
AB  - A host of abnormalities of renal structure and function accompanies advancing
      age. An appreciation of methodologic considerations, including population
      selection, that might confound the assessment of the effects of aging on renal
      function has prompted a recent reappraisal. Earlier studies assessed the effects
      of aging by utilizing cross-sectional studies and institutionalized elderly
      subjects, with their attendant drawbacks. Recent longitudinal studies have
      utilized appropriate patient cohorts, selected for lock of renal disease,
      including potential kidney transplant donors. These studies indicate that the
      morphological and functional changes of aging tend to be less marked than
      previously thought. The common denominator of these functional changes is a
      diminution in renal reserve, along with constraints on the kidney's ability to
      respond appropriately to challenges of either excesses or deficits. Although
      these alterations are unlikely to be of major clinical consequence under everyday
      conditions, they attain clinical significance when residual renal function is
      challenged by the superimposition of an acute illness. Finally, it should be
      emphasized that elderly patients frequently suffer from comorbid conditions, such
      as hypertension and heart disease, that may be additive to the changes of aging,
      thereby amplifying these abnormalities.

PMID- 8866402
TI  - Medullary sponge kidney associated with congenital hemihypertrophy.
AB  - Medullary sponge kidney is a developmental disorder characterized by ectatic and
      cystic malformation of the collecting ducts and tubules. Clinical manifestations
      include urinary tract infections, renal stones, and hematuria. It can be
      associated with other developmental disorders. A case of medullary sponge kidney
      associated with congenital hemihypertrophy, complicated by nephrocalcinosis and
      nephrolithiasis, is reported here.

PMID- 8866403
TI  - Hypertension may be transplanted with the kidney in humans: a long-term
      historical prospective follow-up of recipients grafted with kidneys coming from
      donors with or without hypertension in their families.
AB  - In several genetic hypertensive rat strains, transplantation studies have
      established that the kidney carries at least a portion of the genetic message for
      hypertension. In man it has, of course, been more difficult to obtain clearcut
      results. This historical prospective observational study, double-blinded for
      knowledge of donors' and recipients' family history for hypertension, concerns 85
      transplanted patients, not treated with cyclosporine and with stable renal
      function, followed up for an average of 8 yr. Both the donors' and the
      recipients' families were carefully characterized for presence or absence of
      hypertension. After transplantation, in recipients without hypertension in their
      own families, a kidney coming from a "hypertensive" family determines less
      withdrawal and more introduction of antihypertensive therapy (AHT) than a kidney
      from a "normotensive" family (odds ratio for AHT introduction 5.0, confidence
      interval, 1.4 to 17.8; P = 0.017). In recipients with familial hypertension, the
      origin of the kidney does not influence the prevalence of hypertension after
      transplantation. More detailed analyses show that, in recipients without familial
      hypertension, the transplantation of a "hypertensive" kidney determines a tenfold
      larger increase in the requirement of antihypertensive therapy than the
      transplantation of a "normotensive" kidney, to obtain a similar blood pressure
      control (P = 0.003). This results is confirmed by the analysis of time-profile
      trends for antihypertensive therapy, adjusted for missing data, in the most
      clinically stable period (2nd to 10th yr after transplantation). The transmission
      of familial hypertension with the kidney is thus seen only in recipients coming
      from "normotensive" families, because a familial tendency for hypertension blunts
      the effect of receiving a "hypertensive" kidney.

PMID- 8866404
TI  - Gender discrepancies in living related renal transplant donors and recipients.
AB  - Renal transplantation is the most successful treatment strategy for patients with
      ESRD to improve survival and quality of life. The study presented here examines
      the relationship of gender and living related (LR) transplantation donor and
      recipient rates in the United States. National data from the United States Renal
      Data System (USRDS) were used for this study. All LR transplants occurring
      between 1991 and 1993 among blacks and whites were included (N = 6193).
      Transplantation and donation rates for men and women were calculated. Poisson
      regression was used to calculate female/male transplantation and donation rate
      ratios. Overall, women were 10% less likely to receive a LR transplant than men
      (rate ratio [RR] = 0.90, P < 0.001). This gender difference increased over time
      from 1991 (Female/Male RR = 0.95, P = not significant [NS]) to 1993 (RR = 0.85, P
      < 0.001). In contrast, women were significantly more likely to donate a kidney
      than men (RR = 1.28, P < 0.001 and RR = 1.29, P < 0.001 among whites and blacks,
      respectively). Analyses by age subgroups revealed that only among ESRD patients
      aged 20 to 44 yr was the likelihood of receiving a LR kidney transplant equal for
      men and women. Higher donation rates among women compared with men were observed
      in all donor age and race subgroups except young blacks (aged 0 to 19 yr).
      Recipient gender appeared to influence donation rates. The female-to-male
      relative donation rates were higher when donations were to female, compared with
      male, recipients. This study of national data suggests an imbalance in LR
      donation and transplantation between men and women. Women are more likely to
      donate a kidney but are less likely to receive a LR transplant than men. Several
      potential explanatory factors are explored. These findings suggest a need for the
      development of gender-appropriate interventions to encourage donation among men
      and LR transplantation among women, to ultimately facilitate greater use of this
      ESRD treatment modality.

PMID- 8866405
TI  - Renal functional reserve in kidney and heart transplant recipients.
AB  - Renal functional impairment paradoxically often seems less severe in kidney than
      in heart-transplant recipients (KTR and HTR, respectively) when both are
      submitted to cyclosporine therapy. Renal functional reserve (RFR), elicited by a
      3-h intravenous amino acid infusion, was examined in 12 KTR and 13 HTR at 7 to 8
      months, appropriately compared with either eight one-kidney or 12 two-kidney
      healthy control subjects (1K.C and 2K.C, respectively). Baseline GFR was 54 +/- 4
      mL/min in KTR and 71 +/- 4 mL/min in HTR (P < 0.05). During amino acid infusion,
      the maximum increase in GFR (which represented RFR) was 17 +/- 3 mL/min in both
      KTR and HTR (P < 0.001). RFR in KTR was 96 +/- 18% of that in 1K.C, whereas RFR
      in HTR was only 59 +/- 9% of that in 2K.C. Effective RPF increased (41 +/- 8
      mL/min, P < 0.001), and renal vascular resistances decreased (48 +/- 17 mm Hg/L
      per min, P < 0.05) in KTR but not in HTR. These results demonstrate that both KTR
      and HTR possess a renal reserve but that the single renal graft in KTR retains a
      proportionally higher baseline GFR and a better ability to exhibit a RFR than the
      two native kidneys in HTR. This dissimilar impairment could result from slightly
      higher cyclosporine dosage, activation of the intact renal sympathetic
      innervation accentuated by cardiac denervation, renal consequences of former
      heart failure and potential alterations in the cardiac graft function, and/or
      higher prevalence of hypertension and additive therapies in HTR.

PMID- 8866406
TI  - Effects of endothelin in radiocontrast-induced nephropathy in rats are mediated
      through endothelin-A receptors.
AB  - A role for endothelin in the pathogenesis of radiocontrast-induced nephropathy
      has been suggested by several studies, but the specific contributions of
      endothelin-A and endothelin-B receptors to the changes in renal function induced
      by endothelin in this form of renal failure have not been defined. This study
      examined the effects of the nonselective endothelin receptor antagonist SB
      209,670, and the less potent, but selective, endothelin-A receptor antagonist BMS
      182,874 in radiocontrast-induced nephropathy in rats. The doses used in this
      study were chosen from pressor testing data. BMS-182,874 (100 mumol/kg, iv) and
      SB-209,670 (30 mumol/kg, iv) maximally inhibited the endothelin-1-induced pressor
      response in rats. BMS-182,874 had no effect on the endothelin-B-mediated
      depressor response, whereas SB-209,670 abolished it. These results suggest that
      this is an endothelin-A selective dose of BMS-182,874, and an endothelin-A/B
      inhibitory dose of SB-209,670. Radiocontrast-induced nephropathy was produced in
      anesthetized rats (N = 6/group) by intravenous injection of indomethacin (5.0
      mg/kg), the nitric oxide synthesis inhibitor N-nitro-L-arginine methyl ester
      (10.0 mg/kg), vehicle or antagonist, and the radiocontrast agent lopamidol (2,9 g
      iodine/kg). GFR was partially protected (P < 0.05) by BMS-182,874 (-43 +/- 3.0%
      change from baseline) compared with vehicle (-65 +/- 6.0%). The decrease in GFR
      in SB-209,670-treated rats that received lopamidol was intermediate between the
      other two groups. The fall in RPF induced by lopamidol was unchanged by either
      antagonist. The marked diuresis in lopamidol treated rats (630 +/- 125.1%) was
      reduced (P < 0.01) by BMS-182,874 (176 +/- 77.1%) or SB-209,670 (173 +/- 60.1%).
      Kidneys were collected for histopathologic evaluation approximately 1 h after
      lopamidol administration, and the percentage of medullary tubular ascending limbs
      (mTAL) with morphologic features of necrosis were enumerated by semiquantitative
      analysis. The percentage of mTAL necrosis was significantly decreased in the BMS
      182,874- or SB-209,670-treated rats (P < 0.01) compared with vehicle plus
      lopamidol-treated animals. In summary, endothelin-A receptor blockade with a
      highly selective, well-characterized endothelin-A receptor antagonist partly
      protected GFR, and reduced the marked diuresis and mTAL necrosis in radiocontrast
      induced nephropathy in rats. Administration of a nonselective endothelin receptor
      antagonist provided essentially equivalent ameliorative effects in this model,
      suggesting that blockade of endothelin-B receptors did not yield any additional
      protection. These results are consistent with the hypothesis that endothelin-A
      receptors mediate endothelin-induced changes in renal function and structure in
      this acute model of radiocontrast-induced nephropathy.

PMID- 8866407
TI  - Localization of sites of enhanced expression of endothelin-1 in the kidney of
      DOCA-salt hypertensive rats.
AB  - Although the role of endothelin-1, a potent vasoconstrictor peptide, in
      hypertension remains unclear, there is evidence of its involvement in
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats, in which enhanced
      vascular production of endothelin-1 has been documented. The study presented here
      examined endothelin-1 gene expression in the kidney in DOCA-salt hypertensive
      rats by in situ hybridization histochemistry. A high specific activity 35S
      labeled complementary RNA probe was used. Significant increases in abundance of
      endothelin-1 mRNA transcripts were found in the endothelium of renal vessels, and
      in capillary endothelial and mesangial cells of glomeruli of the remaining kidney
      of DOCA-salt hypertensive rats, in comparison with unilaterally nephrectomized
      control rats. Enhanced expression of the endothelin-1 gene in the kidney of DOCA
      salt hypertensive rats may participate in abnormalities of renal function in this
      model of hypertension, and thus contribute to the development and maintenance of
      elevated blood pressure.

PMID- 8866408
TI  - Sexual experience of the chronic peritoneal dialysis patient.
AB  - The actual and desired frequency of intercourse was studied in 68 randomly
      selected chronic peritoneal dialysis (CPD) patients. The results were correlated
      with standard measures of depression (Beck Depression inventory), anxiety
      (Patient Related Anxiety Scale), physical symptoms (Kupfer-Detre System 2),
      adequacy of dialysis (KT/Vurea) and nutrition (serum albumin level). In addition,
      patients assessed their quality of life (PAQOL) using an 1 to 10 analog scale.
      The mean +/- SD age of all patients studied was 54 +/- 11 yr, the mean dialysis
      duration was 24 +/- 24 months; 46% of the patients were female, and 34% were
      diabetic. Sixty-three percent of the patients reported never having intercourse
      (Group 1), 19% reported having intercourse < or = two times per month (Group II),
      and 18% reported having intercourse > two times per month (Group III). Dialysis
      duration, serum albumin level, KT/Vurea, and age were not significantly different
      among the three groups. Nearly 50% of patients in Group I desired to have
      intercourse, and 54% of the patients in Group II desired to have intercourse more
      frequently, Group I patients had significantly higher depression and anxiety
      scores, more physical symptoms, a poorer overall PAQOL, and less satisfaction
      with their sexual activity than Group III patients. These results suggest that
      there is a high prevalence of sexual difficulties in CPD patients. Patients not
      having intercourse have a poorer quality of life and higher degree of depression
      and anxiety than patients having intercourse more than two times per month.

PMID- 8866409
TI  - Risk factors for vascular disease and arteriovenous fistula dysfunction in
      hemodialysis patients.
AB  - Vascular access dysfunction is an important cause of morbidity for dialysis
      patients and a major contributor to hemodialysis cost. Thrombosis is a leading
      cause of vascular access failure, and usually results from stenotic lesions in
      the venous outflow system. This study was designed to explore the impact of serum
      levels of various risk factors for thrombosis and accelerated fibrointimal
      hyperplasia on progressive stenosis, and the subsequent thrombosis of
      hemodialysis fistula. A cross-sectional and 2-yr prospective pilot study was
      performed in 30 nondiabetic hemodialysis patients with primary arteriovenous
      fistula. Venous dialysis pressure, urea recirculation, color Doppler sonography,
      and angiography were used to monitor vascular access patency. Eleven patients
      (37%) developed a progressive stenosis in the venous circuit, which was
      complicated by thrombosis in three patients. Compared with the patients without
      fistula dysfunction, these patients had higher serum levels of monocyte
      chemoattractant protein-1 and interleukin-6, two cytokines that regulate the
      proliferation of vascular smooth muscle cells, which is the key mechanism in the
      pathogenesis of fistula stenosis. In addition, they had hyperinsulinemia,
      hyperlipidemia, and increased plasma levels of two hemostasis-derived risk
      factors for thrombosis: plasminogen activator inhibitor type 1 and factor VII.
      Monocyte chemoattractant protein-1, interleukin-6, plasminogen activator
      inhibitor type 1, factor VII, triglycerides, and the ratios for cholesterol/HDL
      cholesterol, apolipoprotein (apo) A-I/ apo C-III, apo A-I/apo B, and
      glucose/insulin were independent predictors of fistula dysfunction. This study
      demonstrates the influece of cytokines, hemostasis-derived vascular risk factor,
      hyperinsullnemia, and abnormallties of lipids and apolipoproteins on primary
      fistula survival. The assessment of these factors might be useful for the
      identification of the patients at risk of fistula stenosis and thrombosis.

PMID- 8866410
TI  - Is erythropoietin a survival factor for red blood cells?
AB  - Recombinant human erythropoietin (rhuEPO) therapy has been reported to maintain
      corrected hematocrit values by increasing the length of red blood cell (RBC)
      survival. This article presents a controlled study that assessed the RBC survival
      before, during, and after termination of prolonged rhuEPO treatment of chronic
      hemodialysis patients. Two groups of 20 patients were studied. The hematocrit
      value of each patient was below 28 vol%. One group (Group A) was treated with
      rhuEPO for 1 yr and then treatment was stopped because of the unavailability of
      the drug. The second group (Group B) was treated for 2 yr. Epoetin beta was
      administered subcutaneously. The initial dose was 20 U per kg body weight three
      times weekly. Upon reaching the target hematocrit value of 30 to 35 vol%, the
      dose was individualized for each patient, to maintain target range. RBC survival
      was determined by the chromium-51 technique. In Group A, RBC survival was
      determined: (1) before, (2) at 12 months, and (3) 1 yr after cessation of rhuEPO
      treatment. In Group B, RBC survival was determined: (1) at 24 months of therapy,
      and (2) 1 yr after cessation of rhuEPO treatment. RBC survival increased
      significantly in both patient groups under rhuEPO treatment. After cessation of
      therapy, the RBC survival decreased to pretreatment values. During the correction
      period, reticulocyte counts increased significantly in both groups. Over the
      maintenance period, they slightly decreased, and after termination of rhuEPO
      therapy, they decreased to the pretreatment values. The results of this study
      could suggest the possibility that RBC survival was prolonged by the action of
      EPO on the erythroid progenitors, resulting in the production of RBC with
      improved viability.

PMID- 8866411
TI  - Kidney iron status in passive Heymann nephritis and the effect of an iron
      deficient diet.
AB  - In the study presented here, the iron status in the kidney in passive Heymann
      nephritis, a complement-dependent model of membranous nephropathy, was examined.
      To examine whether the effect of immune injury on iron status has a pathogenic
      role, the effect of an iron-deficient diet was also determined. Injection of the
      anti-Fx1A antibody (10 mg/100 g body wt) in Sprague-Dawley rats resulted in no
      change in the serum iron level, a marked increase in the urinary excretion rate
      of iron, a marked increase in non-heme iron content of kidney cortex, and a
      marked increase in the non-heme iron level in tubules. These increases in iron
      were prevented by feeding the rats an iron-deficient diet. In the rats fed a
      normal iron diet and injected with anti-Fx1A-lgG, there was no significant change
      in the non-heme iron level in glomeruli. However, an iron-deficient diet resulted
      in a significant decrease in the non-heme iron level in glomeruli, compared with
      its respective control. In addition, an iron-deficient diet significantly reduced
      urinary protein excretion rate (Day 5: iron-replete, 68 +/- 12 mg/24 h, N = 12;
      iron-deficient, 36 +/- 11, N = 10, P < 0.05) in the complement-dependent immune
      phase of the glomerular injury. Taken together, these data indicate a marked
      alteration in the iron status in the kidney and suggest an important role of iron
      in glomerular injury of passive Heymann nephritis.

PMID- 8866412
TI  - Ovariectomy decreases plasma triglyceride levels and both prevents and alleviates
      glomerular disease in uninephrectomized female analbuminemic rats.
AB  - Female Nagase analbuminemic rats (NAR) are profoundly hypertriglyceridemic and
      develop proteinuria and glomerulosclerosis when aging and after uninephrectomy
      (UNX). Ovariectomy (OVX) markedly decreases plasma triglyceride levels in this
      species. This study evaluated whether decreasing triglyceride levels by OVX could
      prevent renal disease or alleviate its progression in UNX female NAR. Female NAR
      underwent OVX at 0, 12, 24, or 36 wk after UNX. In the absence of OVX, the
      animals developed progressive proteinuria from 18 wk after UNX and showed
      extensive glomerular sclerosis, lipid deposition, and hypertrophy at euthanasia
      (49 wk after UNX). These changes were prevented by OVX carried out at 0 or 12 wk,
      and attenuated by OVX at 24 wk after UNX. If performed at 36 wk after UNX, OVX
      had no effect on glomerulosclerosis, although it reduced proteinuria. In 95% (20
      of 21) of the rats with proteinuria over 10 mg/day, proteinuria decreased in the
      first 6 wk after OVX. The percentage decrease in proteinuria correlated inversely
      with the glomerulosclerosis score at euthanasia (r = -0.58, P < 0.01). OVX had no
      effect on hyperfiltration and hyperperfusion in the UNX rats. OVX consistently
      reduced plasma triglyceride levels in rats both with and without proteinuria, and
      it also reduced plasma cholesterol, but only in conjunction with reduction in
      proteinuria. It was concluded that OVX in UNX female NAR prevents
      glomerulosclerosis if performed before proteinuria and attenuates further
      development of established renal disease if performed in a timely manner. This
      study's data suggest that in UNX female NAR, the lowering of plasma triglyceride
      levels plays a central role in the renoprotective action of OVX.

PMID- 8866413
TI  - Accumulation of albumin-linked and free-form pentosidine in the circulation of
      uremic patients with end-stage renal failure: renal implications in the
      pathophysiology of pentosidine.
AB  - Pentosidine is an advanced glycation end product and its formation is shown to be
      closely related to oxidative processes. Recent studies have shown that
      pentosidine levels are increased not only in plasma and matrix proteins from
      diabetic patients, but also markedly in nondiabetic hemodialysis patients.
      Currently, the mechanism of accumulation and kinetics of pentosidine formation in
      hemodialysis patients remain unknown. Gel filtration of uremic plasma revealed
      that plasma pentosidine exists in the albumin fraction (approximately 90%) and,
      interestingly, in free form (approximately 5%) as well. Plasma free pentosidine
      was undetectable in subjects with normal renal function. There was a significant
      correlation between the plasma levels of albumin-linked and free pentosidine in
      hemodialysis patients. Kinetic studies indicated that dietary pentosidine was
      absorbed into the circulation and that, after either oral or intravenous
      administration of pentosidine to intact or nephrectomized rats, the plasma free
      pentosidine level was closely linked to the level of renal function. These
      findings demonstrate that: (1) Pentosidine accumulates as albumin-linked and in
      free form in the circulation of uremic patients; (2) dietary pentosidine can be
      absorbed into the circulation, thus being one possible origin of circulating free
      pentosidine; (3) free pentosidine may accumulate as a result of decreased
      glomerular filtration; and (4) the mechanism of accumulation of albumin-linked
      pentosidine is not related to high glucose levels. It suggests the simultaneous
      accumulation, during renal failure, of either unknown pentosidine precursor(s) or
      catalyst(s) of glycoxidation, independent of glucose.

PMID- 8866414
TI  - Captopril reverses high-glucose-induced growth effects on LLC-PK1 cells partly by
      decreasing transforming growth factor-beta receptor protein expressions.
AB  - Transforming growth factor beta (TGF-beta) may be important in the pathogenesis
      of diabetic nephropathy, and captopril is effective in treating this disorder.
      However, the mechanisms of this therapeutic effect as related to TGF-beta and its
      receptors are not known. Thus, the effects of captopril on cellular growth, TGF
      beta 1, and TGF-beta receptors were studied in LLC-PK1 cells cultured in normal
      (11 mM) or high glucose (27.5 mM). This study found that glucose dose-dependently
      inhibited cellular mitogenesis while inducing hypertrophy in these cells at 72 h
      of culture, concomitantly with enhanced TGF-beta 1 messenger RNA (mRNA) and TGF
      beta receptor Types I and II protein expressions. Captopril dose-dependently (0.1
      to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these
      cells. Moreover, captopril also decreased TGF-beta receptor Types I and II
      protein expressions dose-dependently. However, TGF-beta 1 mRNA was not affected
      by captopril. It was concluded that high glucose decreased cellular mitogenesis
      while increasing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF
      beta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-induced
      growth effects by decreasing TGF-beta receptor protein expressions.

PMID- 8866415
TI  - Effects of diadenosine polyphosphates on renal function and blood pressure in
      anesthetized Wistar rats.
AB  - In this study, the effects of diadenosine polyphosphates on kidney function were
      examined. Intravenous application of diadenosine hexaphosphate (AP6A) led to a
      significant threefold increase in both urine flow (from 2.45 +/- 0.2 to 13.8 +/-
      0.74 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.41 +/-
      0.12 to 1.52 +/- 0.28 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body
      wt). In contrast, diadenosine triphosphate dose-dependently reduced urine flow
      (from 3.74 +/- 0.3 to 2.57 +/- 0.1 microL/min per 100 g body wt (P < 0.05)) and
      Na+ excretion (from 0.45 +/- 0.1 to 0.13 +/- 0.1 mumol/min per 100 g body wt at a
      dose of 1.0 mg/kg body wt). ATP and the P2y purinoceptor agonist gamma-S-ATP did
      not significantly modulate urine flow and Na+ excretion. alpha, beta-methylene
      ATP, a P2x purinoceptor agonist, significantly increased urine flow from 1.74 +/-
      0.5 to 4.07 +/- 1.51 microL/min per 100 g body wt, whereas Na+ excretion was
      unaffected. The effects were independent of alterations in GFR. Pretreatment with
      indomethacin (2.0 mg/kg body wt iv) completely abolished the effects of AP6A on
      urine flow and Na+ excretion. Similarly, pretreatment with the endothelin
      antagonist bosentan abolished the effects of AP6A on both urine flow and Na+
      excretion, whereas suramin had no effects on the AP6A-induced increase in urine
      flow. In conclusion, diadenosine polyphosphates exert specific actions on urine
      flow and Na+ excretion that are different from the effects of ATP. AP6A may
      partially influence renal function by stimulating prostaglandin and endothelin
      release.

PMID- 8866416
TI  - Extrarenal potassium homeostasis with maximal exercise in end-stage renal
      disease.
AB  - Serum potassium levels rise substantially during vigorous exercise as a result of
      the release of potassium from contracting muscle cells. Widespread use of
      erythropoietin has allowed for increased exercise capacity in patients with ESRD,
      raising the concern for severe exertional hyperkalemia. The aim of this study was
      to determine whether ESRD is associated with alterations in potassium and the
      neurohumoral mediators of extrarenal potassium disposal with maximal exercise.
      Eight stable hemodialysis patients (aged 37 +/- 16 yr, mean +/- SE) and eight
      healthy control subjects (aged 44 +/- 13 yr) exercised to exhaustion, using a
      graded cycle ergometer. There were no significant differences in exercise
      performance between groups as assessed by peak work rate, maximal oxygen
      consumption, and rate pressure product. Although the baseline potassium level was
      higher in the dialysis group (5.0 +/- 0.2 mEq/L) than in control subjects (4.5 +/
      0.1 mEq/L), both groups had a similar pattern of increase during exercise (with
      an increment of approximately 1 mEq/L) and a similar return to baseline after
      exercise. However, the dialysis patients had higher basal norepinephrine levels
      (820 +/- 104 versus 441 +/- 56 pg/mL, P < 0.01) and a greater response to
      exercise (3122 +/- 429 versus 1696 +/- 424 pg/mL, P < 0.01), higher basal insulin
      levels (11 +/- 1 versus 7 +/- 1 microU/mL, P < 0.05), higher insulin post
      exercise levels (19 +/- 3 versus 11 +/- 1 microU/mL, P < 0.05), and higher basal
      aldosterone levels (621 +/- 250 versus 109 +/- 13 pg/mL, P < 0.05) with an
      increase response to exercise (1100 +/- 350 versus 350 +/- 17 pg/mL, P < 0.05).
      In summary, despite higher basal potassium, dialysis patients have normal
      potassium responses to maximal exercise. More vigorous insulin, catecholamine,
      and aldosterone levels may contribute to the maintenance of extrarenal potassium
      homeostasis in ESRD.

PMID- 8866417
TI  - Vaccine-induced hepatitis B surface antigen positivity in adult hemodialysis
      patients: incidental and surveillance data.
AB  - This report describes hepatitis B vaccinations that resulted in transient
      hepatitis B surface antigen positivity in six adult hemodialysis patients.
      Initially, three patients were incidentally discovered to be hepatitis B surface
      antigen-positive temporally related to hepatitis B vaccination. Two other
      patients who displayed transient positivity were among 15 hemodialysis patients
      under prospective surveillance after receiving a dose of hepatitis B vaccine. The
      sixth patient was negative for hepatitis B surface antigen when monitored in the
      prospective surveillance group but was incidentally found to be positive after a
      nonsurveillance dose of the vaccine. All positive cases cleared hepatitis B
      surface antigen within 20 days of vaccination. In our search of the literature,
      this is the first report of hepatitis B vaccine inducing hepatitis B surface
      antigen positivity in adult hemodialysis patients. Because this study proposes
      that this transient surface antigen positivity is vaccine-induced and not a true
      hepatitis B infection, we recommend that renal dialysis patients not be screened
      for hepatitis B surface antigen for at least 21 to 28 days after hepatitis B
      vaccination. As well, blood donors should not donate blood in this early
      postvaccination period. These guidelines would incorporate a measure of safety to
      prevent individuals in the early postinoculation period from being erroneously
      labeled as having hepatitis B viral infections.

PMID- 8866418
TI  - Performance characteristics of a dialysis-related amyloidosis questionnaire.
AB  - To evaluate the effects of beta-2 microglobulin amyloidosis on functional status,
      a 19-item self-administered questionnaire exploring two major domains-symptoms
      and disability-was developed as part of this study. Fifteen patients with
      dialysis-related amyloidosis (DRA) were identified and compared with 15 age
      matched control subjects who had been on hemodialysis for less than 24 months.
      Demographic data, Charlson comorbidity scores, and other clinical and laboratory
      variables were recorded. Total dialysis-related amyloidosis questionnaire (DRAQ)
      score (52.1 +/- 16.3 versus 24.4 +/- 6.2, P < 0.0001) and the scores of the
      symptom (24.5 +/- 7.0 versus 11.5 +/- 2.3, P < 0.0001) and disability (27.5 +/-
      10.8 versus 12.9 +/- 4.0, P < 0.0001) subscales were markedly increased among
      patients with DRA. Baseline characteristics among case and control subjects were
      similar, except for serum creatinine concentration, which tended to be lower
      among patients with DRA (8.9 +/- 2.6 versus 11.5 +/- 2.3 mg/dL, P = 0.07).
      Instrument reliability and internal consistency were high. With a total DRAQ
      score of 30 or more, the sensitivity and specificity of the instrument were 93%
      and 80%, respectively. The DRAQ is a reliable, internally consistent, and valid
      instrument that may be suitable for population screening and clinical practice.

PMID- 8866419
TI  - Noninvasive measurement of blood volume in hemodialysis patients.

PMID- 8866420
TI  - Prostaglandins and renal damage.

PMID- 8866421
TI  - Hematologic disorders associated with ischemic stroke.
AB  - Hematological disorders underlie a small proportion of all ischemic strokes. The
      association of these coagulation abnormalities with ischemic stroke is not always
      clear. The etiology of stroke still remains uncertain in a large number of cases
      and proper screening for coagulation abnormalities and the discovery of new
      coagulation disorders will probably increase the rate of strokes attributable to
      these causes. Since large case-control studies with unselected and consecutive
      stroke patients from different ethnic origins have not yet been performed to
      determine the role of coagulation abnormalities in ischemic stroke, our knowledge
      is dependent on case reports and small series of mostly younger patients.
      Extensive hematologic evaluation of unselected stroke patients will likely yield
      little useful information and be too expensive. Every stroke patients needs a
      careful evaluation, and in selected cases, this should include coagulation
      parameters. Patients with unexplained strokes after a careful evaluation,
      previous thrombotic episodes, or a positive family history for thrombosis, are
      good candidates for further coagulation studies. As long as the hypercoagulable
      state persists, both arterial and venous thromboembolic recurrences can be
      expected. Many of these patients may benefit from anticoagulants. In patients
      with hereditary coagulation disorders, studies should be extended to close
      relatives. Since some coagulation tests are fairly expensive, provide only
      equivocal data, and are not widely available, we advise a step-by-step approach
      starting with the patient and family history.

PMID- 8866422
TI  - Insulin partially reverses deficits in peripheral nerve blood flow and conduction
      in experimental diabetes.
AB  - Decreased nerve blood flow may be a pathogenetic factor in diabetic neuropathy.
      Previously it was shown that insulin treatment, commenced at the onset of
      streptozotocin-diabetes, prevents the development of a nerve blood flow deficit
      in the diabetic rat. The present study sought to determine the effect of short
      term (one month) and acute (one hour) insulin reversal treatment on nerve blood
      flow deficits in streptozotocin-diabetes. Sciatic nerve blood flow was assessed
      using laser Doppler flowmetry. Treatment was initiated after one month of
      diabetes. One month of reversal insulin treatment ameliorated nerve laser Doppler
      flux (NDF) deficits; in untreated diabetic rats NDF was 51% of that in control
      animals (P < 0.01), in insulin-treated diabetic rats NDF was 85% of control
      values (P < 0.01 vs. untreated diabetic, P < 0.05 vs. control). In association
      with blood flow increases, we found a significant amelioration of motor (P < 0.05
      vs. untreated diabetic) and sensory (P < 0.01 vs. untreated diabetic) nerve
      conduction velocities but not of exaggerated resistance to hypoxic conduction
      block. Insulin partially reversed hyperglycaemia and sciatic nerve polyol and
      sugar levels. In a second experiment, in rats with one month of diabetes, acute
      infusion of insulin led to a 47% (P < 0.001 vs. pre-insulin values) reduction of
      plasma glucose. This fall in plasma glucose was accompanied by a 38% (P < 0.05
      vs. pre-insulin values) increase in NDF. Sensory nerve conduction velocity was
      marginally increased (6%, P < 0.05 vs. pre-insulin values) after insulin
      infusion, but motor conduction velocity was not. The data indicate that insulin
      can partially reverse deficits in nerve blood flow and conduction in diabetic
      rats.

PMID- 8866423
TI  - Enhanced superoxide dismutase-2 immunoreactivity of astrocytes and occasional
      neurons in amyotrophic lateral sclerosis.
AB  - The recent discovery of missense mutations in the superoxide dismutase (SOD)-1
      gene as a cause of familial amyotrophic lateral sclerosis (ALS) and the ensuing
      description of transgenic SOD-1 mutant mouse models have focussed scientific
      interest on free radical scavenging mechanisms in all other familial (FALS) and
      sporadic (SALS) forms of the disease. We have compared the presence of
      intracellular cytosolic copper-zinc SOD-1 and mitochondrial manganese SOD-2 in
      the CNS from FALS and SALS patients and from non-neurological controls by
      immunohistochemical assessment, in the knowledge that no SOD-1 mutations have
      been found in any of 18 Dutch ALS pedigrees. ALS specimens from the motor cortex
      and the spinal cord presented enhanced SOD-2 immunoreactivity, especially of
      astrocytes and occasionally of neurons. Astrocyte staining appeared to be
      increased at the cerebral cortical and the spinal cervical and lumbar levels, but
      was only slightly increased in the thoracic anterior horns and not at all in the
      brain stem. This indicates that, by the time of death, the disease had burnt out
      in the brain stem and thoracic cord. Increased staining of neurons was limited to
      the small lateral and dorsal nuclei of the spinal cord. FALS and SALS cases
      exhibited the same staining patterns. SOD-1 immunoreactivity did not differ
      between disease and control specimens. SOD-1 and -2 staining was normal in the
      ALS cortical, brain stem and spinal motoneurons. This suggests that SALS and non
      SOD-1 mutant FALS are not accompanied by loss of SOD-1 or -2 protein. An enzyme
      linked immunosorbent assay revealed no differences in SOD-1 and SOD-2 levels
      between ALS patients and controls. Our major finding of locally increased SOD-2
      immunoreactivity of astrocytes in FALS and SALS specimens, probably reflects
      reactive fibrillary and protoplasmatic gliosis in areas of ongoing degeneration
      but may also result from an attempt at compensation for free radical injury.

PMID- 8866424
TI  - alpha-Sarcoglycan (adhalin) deficiency: complete deficiency patients are 5% of
      childhood-onset dystrophin-normal muscular dystrophy and most partial deficiency
      patients do not have gene mutations.
AB  - alpha-Sarcoglycan (adhalin), a 50-kDa component of the dystrophin-associated
      complex of proteins, participates in the stabilization of the myofiber plasma
      membrane in the membrane cytoskeleton. Deficiencies of alpha-sarcoglycan cause a
      subset of childhood-onset muscular dystrophy (SCARMD) cases. However, secondary
      deficiencies of alpha-sarcoglycan are common. To begin to establish the rates of
      false positives (secondary deficiencies), we used immunofluorescence to screen 30
      Italian dystrophin-normal muscular dystrophy patient biopsies and identified 4
      patients with partial alpha-sarcoglycan deficiency and 2 patients with complete
      deficiency. The entire alpha-sarcoglycan gene was screened for mutations using RT
      PCR and SSCP of messenger RNA isolated from muscle biopsies in each of the six
      patients. Aberrant SSCP conformers and novel mutations were found only in the two
      complete immunohistochemical deficient patients. One patient was homozygous for a
      R34H amino acid substitution, while the other was a compound heterozygote (R77C,
      D97G). These three missense mutations, with additional mutations we and others
      have previously described, are all localized in the extracellular domain of alpha
      sarcoglycan, and most result in the loss or gain of a positively charged amino
      acid. These data have strong implications for structure/function maps of the
      alpha-sarcoglycan molecule. Our results suggest that most patients showing
      partial alpha-sarcoglycan deficiency exhibit this as a secondary consequence of
      genetically distinct disorders. In support of this, we show biochemical data
      indicating that secondary deficiency patients show decreased immunostaining with
      antibodies directed against alpha-sarcoglycan, while having nearly normal
      quantities of alpha-sarcoglycan protein on immunoblot. This data also suggests
      that approximately 5% of childhood-onset dystrophin-normal muscular dystrophy
      patients will show a primary alpha-sarcoglycan deficiency.

PMID- 8866425
TI  - A quantitative morphometrical study of neuron degeneration in the substantia
      nigra in Parkinson's disease.
AB  - We studied the pigmented neurons of the substantia nigra (SN) from 8 controls and
      20 patients with Parkinson's disease (PD) using a computerized morphometric
      methodology. On the basis of neuronal topography, several anatomic regions were
      outlined in the SN. In these subregions the area, perimeter, diameter of the cell
      bodies and cell numbers were measured and were counted in the controls and PD
      patients. The measurements were made at the level of the exit of the third
      cranial nerve from the brain stem. In PD patients, when the whole SN was
      considered, the mean area, mean perimeter and diameter of the pigmented cell
      bodies were significantly reduced by 35%, 20% and 21% respectively from the
      control mean values. Regionally, the pigmented neuron area in the medial ventral
      part (VM), medial dorsal part (DM), lateral ventral part (VL), lateral dorsal
      part (DL) and pars lateralis part (PL) showed a significant reduction of 33-41%
      as compared to controls. In these subregions, a significant decrease in PD
      patients from the control mean values was seen both in the pigmented neuron
      perimeter, by 19-26%, and the diameter by 19-25%. This decrease in cell size
      suggests that, in PD patients, the remaining pigmented neurons in the SN are in a
      process of degeneration and atrophy. In PD patients the number of pigmented
      neurons in the whole SN decreased about 76% from control values. Evaluation of
      the influence of cell size on the apparent quantity of cells in sections
      indicates, however, that in PD patients the impact of true loss of pigmented
      neurons is far more dramatic than the impact of their decrease in size.

PMID- 8866426
TI  - Cerebral oxygen and glucose metabolism in glycogen storage disease with normal
      acid maltase: case report.
AB  - A 26-year-old male with cardiomyopathy, cervical muscle weakness and mental
      retardation was diagnosed as having glycogen storage disease with normal acid
      maltase on the basis of his clinical, pathological and biochemical findings.
      Positron emission tomography showed that cerebral oxygen metabolism was normal,
      while cerebral glucose metabolism was decreased in the cerebral cortexes. The
      decrease of the glucose metabolic rate may reflect an abnormality of cerebral
      glucose metabolism in this disorder and may be related to mental retardation,
      which is one of the characteristic symptoms.

PMID- 8866427
TI  - Is ataxic gait the predominant presenting manifestation of Creutzfeldt-Jakob
      disease? Experience of 14 Chinese cases from Taiwan.
AB  - Creutzfeldt-Jakob disease (CJD) is caused by an unusual prion protein. Rare CJD
      cases have been reported in Chinese individuals. This report describes the
      clinical manifestations of 14 Chinese individuals with clinically definite CJD
      from the National Taiwan University Hospital during the period 1976-1995. It is
      the largest case series of Chinese CJD up to now. All these patients fulfil the
      clinical definite diagnosis of CJD proposed by Brown et al. (1986), including
      rapidly evolving dementia, myoclonus, periodic electroencephalographic (EEG)
      activity (0.5-2 Hz) and death within 12 months. The clinical characteristics of
      the present series, including age at onset, sex ratio, duration, initial
      symptoms, neurological signs, EEG abnormalities, and neuroimaging studies were
      similar to those reported in other countries. However, there is a high incidence
      of initial ataxic gait as the presentation in our patients. Eight (57%) out of 14
      patients initially had gait ataxia alone or in association with dementia. CJD
      should be considered in the differential provisional diagnosis of any middle-aged
      patient with a progressive ataxic syndrome.

PMID- 8866428
TI  - The limit of low speed peripheral nerve elongation; neurological and circulatory
      aspects.
AB  - We studied peripheral nerve elongation of rabbit sciatic nerves. External
      fixators developed in our department were applied to 32 rabbit femurs in vivo.
      The rabbits underwent osteotomy of the femur and were divided into two groups
      subjected to different sciatic nerve elongation speeds: group I (0.45 mm/day) and
      group II (1.35 mm/day). The sciatic nerves were elongated 1.5, 3.0, 4.5, 6.0 and
      7.0 cm by the external fixators, and the corresponding actual percentage of
      elongation of the nerves were 8, 16, 24, 30 and 40%. After elongation, nerve
      electrophysiology, nerve blood flow and pathology were studied. Forty percent
      elongation decreased nerve blood flow to 69 +/- 5.1% of contralateral controls in
      group I and to 20 +/- 4.8% in group II. Although no decrease in motor conduction
      velocity (MCV) was observed at any elongation distance, compound muscle action
      potential (CMAP) amplitude gradually decreased with increasing elongation. In
      group I, after 40% elongation, specimens showed the following pathologic changes:
      thinning of myelin sheath, atrophy and detachment of the axon from the myelin
      sheath. Furthermore, in group II, 40% elongation induced disorganization of the
      myelin sheath and Wallerian degeneration. Consequently 40% elongation was
      regarded as critical at speeds of both 0.45 and 1.35 mm/day.

PMID- 8866429
TI  - Movement-related potential measures of different modes of movement selection in
      Parkinson's disease.
AB  - Movement-related potentials were recorded preceding self-paced voluntary
      movements in patients with Parkinson's disease and in healthy subjects of the
      same age group. We compared the Readiness Potential preceding joystick movements
      in a fixed direction and preceding joystick movements in freely selected
      directions. In normal subjects the Readiness Potential amplitude was higher
      preceding freely selected movements than preceding movements in a fixed
      direction. The Readiness Potential in Parkinson patients failed to be modified by
      the different modes of movement selection. The modulation of the Readiness
      Potential by different ways of preparing for movement might be due to the
      supplementary motor area (SMA) being more strongly engaged by tasks requiring
      internal control of movements than by tasks that are externally structured. The
      results suggest that this task-dependent variation of SMA activity is reduced in
      Parkinson's disease. A failing capacity to adapt SMA activity to different task
      demands has previously been suggested by evidence from positron emission
      tomography studies using similar tasks.

PMID- 8866430
TI  - Characterization of the mitochondrial DNA in patients with multiple sclerosis.
AB  - Mitochondrial DNA (mtDNA) abnormalities with primary pathogenic significance for
      optic nerve atrophy have been detected in inflammatory demyelinating conditions
      indistinguishable from multiple sclerosis (MS). However, the degree of
      involvement of mtDNA alterations in the pathogenesis of MS is not clear. To
      further clarify this question, we sequenced the entire mtDNA in three MS
      patients. A number of nucleotide alterations were defined relative to the
      standard mtDNA sequence in each patient. After excluding the silent mutations and
      common polymorphisms, eight unusual mtDNA variants within the ribosomal (r) RNA,
      transfer (t) RNA or protein encoding regions were identified and characterized.
      Two mutations remained as putative MS related alterations after screening a
      population of 49 patients and 63 controls for the presence of these mutations. An
      A to G transition at nucleotide (nt) 13966 causing a threonine to phenylalanine
      exchange in a non-conserved region of the ND-5 was detected in two independent MS
      patients and in none of the sixty-three controls or in any of the large control
      population in the literature. The second mutation of interest at 14798 is a T to
      C transition changing a phenylalanine to leucine in a relatively conserved domain
      of the cytochrome b. Although it is a known polymorphism, a tendency for
      prominent optic nerve involvement was observed among patients carrying this
      mutation. As we have performed the first complete mtDNA sequence analysis on MS
      patients, we conclude that MS may occur without mtDNA abnormalities of primary
      pathogenic significance. However, contribution of the mtDNA to genetic
      susceptibility or phenotypic presentation of MS is possible in certain subgroups
      of patients, and merits further investigation.

PMID- 8866431
TI  - Multi-system signs and symptoms in X-linked ataxia carriers.
AB  - Neurological, auditory, vestibular and ocular motor examinations were performed
      on 3 definite and 3 possible heterozygous carriers of a previously described X
      linked multi-system disorder with early childhood onset, rapid progression and a
      fatal outcome (Arts et al., 1993). The symptoms, i.e., delayed motor development,
      ataxia, hearing loss and subnormal intelligence, were so evident in 2 of the
      possible carriers that they could be redesignated as probable carriers. Other
      symptoms in the definite and probable carriers were clubfeet, dysarthria,
      intention tremor and abnormal gait, while their signs included
      dysdiadochokinesia, ataxic paraplegia, abnormal muscle tendon reflexes and
      extensor plantar responses. All the symptomatic carriers developed moderate-to
      severe sensorineural hearing loss with normal stapedial reflexes and brain stem
      auditory evoked potentials (BAEPs) in those in whom this could be evaluated.
      Speech discrimination was disproportionally poor unilaterally in one case from
      whom no BAEPs could be obtained because of her degree of hearing loss. Various
      combinations were found of high gain of the vestibulo-ocular reflex, spontaneous
      nystagmus and directional preponderance of vestibularly evoked nystagmus,
      slowing, hypometria or multi-stepping of saccades, saccadic intrusions of eye
      movements (macro square wave jerks, double saccadic pulses), impairment of smooth
      pursuit eye movements and optokinetic nystagmus, and failure of visual fixation
      suppression of vestibularly evoked nystagmus. Such findings indicate major
      involvement of the (vestibulo)cerebellum and the vermis. MRI in one carrier
      showed mild cerebellar atrophy.

PMID- 8866432
TI  - Post-infectious encephalitis with anti-galactocerebroside antibody subsequent to
      Mycoplasma pneumoniae infection.
AB  - Galactocerebroside (Gc) is a major component of myelin in both the peripheral and
      central nervous systems. Although it is regarded as an important glycolipid
      hapten of myelin in rabbit experimental allergic neuritis (EAN), its role in
      human demyelinating diseases is not known. We studied three post-infectious
      encephalitis (PIE) patients related to Mycoplasma pneumoniae infection. All three
      of three patients with encephalitis and M. pneumoniae infection were positive for
      Gc antibodies (100%), while 25% of 32 M. pneumoniae-infected patients without
      neurological disease were positive, and 3.8% of 52 healthy controls. This
      indicates anti-Gc antibody is induced by M. pneumoniae infection. One of the PIE
      patients, who had extraordinary high titer antibody to Gc, showed an extensive,
      diffuse white matter demyelination and poor recovery. Since circulating anti-Gc
      antibody induces central nervous system demyelination in animals with elevated
      antibody titers and disruption of the blood-brain barrier, anti-Gc antibody may
      have an important function in the increased demyelination in PIE patients after
      M. pneumoniae infection.

PMID- 8866433
TI  - Immunohistochemical study of intracytoplasmic inclusion bodies of the thalamus in
      myotonic dystrophy.
AB  - Intracytoplasmic inclusion bodies of the thalamus in eight patients with myotonic
      dystrophy (MyD) were studied immunohistochemically. The intracytoplasmic
      inclusion bodies of the thalamus (thalamic inclusions, TIs) were strongly
      immunostained with anti-ubiquitin antibody (Ab) and some of them were mildly
      stained with anti-microtubule associated protein 1 (MAP 1) and anti-MAP 2
      antibodies. However, TIs did not react with any of the following: anti
      neurofilament protein Ab, anti-tau Ab, anti-paired helical filament Ab, anti
      tubulin Abs (alpha and beta), anti-neuron-specific enolase Ab, anti-glial
      fibrillary acidic protein Ab, anti-synaptophysin Ab, anti-myelin basic protein
      Ab, anti-actin Ab and anti-phosphorylated epitope of neurofilaments Ab. Thus, our
      study demonstrates the unique immunohistochemistry of TIs in MyD which
      differentiates them from other intracytoplasmic inclusions in various
      neurodegenerative disorders.

PMID- 8866434
TI  - Progressive dementia and leucoencephalopathy as the initial presentation of late
      onset hereditary cystatin-C amyloidosis. Clinicopathological presentation of two
      cases.
AB  - Hereditary Cystatin-C Amyloidosis (HCCA) is a genetic disorder in Icelandic
      families in which a defective cystatin-C amyloid protein is deposited in the
      walls of small and middle sized arteries. Cerebral vessels are most affected,
      resulting in recurrent cerebral hemorrhages and infarctions, usually with onset
      of clinical symptoms in the twenties or thirties and a rapidly deteriorating
      clinical course. The disease can be diagnosed by a skin biopsy in symptomatic
      patients. We report two patients (father and daughter) who did not have a known
      family history of the disorder and presented late in life with a progressive
      dementia, associated with cerebral hemorrhages in the younger patient. Cerebral
      MRI and CT scans of this patient showed extensive leukoencephalopathic changes.
      Brain tissue samples from both patients showed immunohistochemical reaction to
      cystatin-C in small and medium-sized cerebral arteries and extensive cortical and
      white matter microinfarctions. The amyloid changes were less severe in the older
      patient and a colocation of beta-amyloid protein and cystatin-C was observed in
      addition to neurofibrillary tangles and senile plaques. Subcortical and cortical
      infarctions were also observed. HCCA may present late in life with progressive
      dementia as the only clinical manifestation, reflecting a multi-infarct syndrome
      secondary to the amyloidosis. A coexpression of cystatin-C and beta protein may
      occur as in other cerebral amyloid disorders, probably as age-specific changes.

PMID- 8866435
TI  - Ipsilateral cortico-cortical inhibition of the motor cortex in various
      neurological disorders.
AB  - We used a paired-pulse magnetic stimulation technique to study ipsilateral
      cortico-cortical inhibition of the motor cortex in 48 patients with various
      neurological disorders and in 20 normal volunteers. In the normal subjects, the
      first subthreshold conditioning stimulus suppressed responses to the second
      suprathreshold test stimulus at interstimulus intervals (ISIs) of 1-5 ms
      (inhibition at short intervals), and facilitated them at ISIs of 8-15 ms
      (facilitation at long intervals). Patients with motor neuron disease, except
      those in whom brain stimulation produced control responses that were generated by
      direct activation of corticospinal neurons (D-waves), had normal inhibition at
      short intervals. Facilitation at long intervals was not elicited in some patients
      with amyotrophic lateral sclerosis. Less inhibition at short intervals and normal
      facilitation at long intervals was found for all the patients with progressive
      myoclonic epilepsy, a condition in which the excitability of cortical inhibitory
      interneurons is thought to be affected. Inhibition at short intervals was
      disturbed, but facilitation at long intervals was intact in the patients with
      movement disorders (Parkinson's disease, corticobasal degeneration, and Wilson's
      disease). In these patients, positron emission tomography (PET) studies showed
      decreased regional cerebral blood flow (rCBF) in the basal ganglia in the relaxed
      state. However, normal suppression was elicited in the patients with Parkinson's
      disease with normal rCBF. In four patients with chorea, the time-course of
      inhibition and facilitation was normal, even though PET studies showed decreased
      rCBF in the basal ganglia in two of them. Normal inhibition could not be elicited
      in patients who had a small lesion in the basal ganglia or in the pathway from
      basal ganglia to the primary motor cortex; the putamen, globus pallidus, and
      supplementary motor cortex. In contrast, patients who had a lesion in a sensory
      system (sensory cortex or sensory thalamus) or in the pontine nucleus had normal
      suppression. We conclude that the results of ipsilateral cortico-cortical
      inhibition with paired magnetic stimulation reflect the excitability of
      inhibitory interneurons in the motor cortex and that outputs from the basal
      ganglia markedly affect this inhibition, but outputs from somato-sensory systems
      or cerebellum do not. Moreover, dysfunction of the corticospinal tract or spinal
      motoneurons does not affect results obtained by the paired magnetic stimulation
      technique when the control responses are generated by I-waves (i.e. descending
      volleys are produced by transsynaptic activation of the corticospinal tract
      neurons.

PMID- 8866436
TI  - Expression of ciliary neurotrophic factor is maintained in spinal motor neurons
      of amyotrophic lateral sclerosis.
AB  - Ciliary neurotrophic factor (CNTF) was originally identified as a potent survival
      factor for a variety of neuronal cell types in vitro and in vivo and in
      particular in spinal motor neurons of embryonic chick and rat. Using a monoclonal
      antibody against CNTF (clone 4-68) we analysed the expression of CNTF in paraffin
      sections of seven human brains and spinal cords immunocytochemically using the
      ABC method and compared these results with sections of the spinal cords of
      patients suffering from amyotrophic lateral sclerosis (ALS). In normal human
      tissue of the central nervous system CNTF immunoreactivity was found in most of
      the motor neurons of the motor cortex and ventral horn, neurons of the nucleus
      oculomotorius, intermediolateralis, thoracicus, ependymal cells as well as in
      smooth muscle cells and endothelial cells of small arteries. A reduced number of
      astrocytes showed a positive immunocytochemical reaction. In peripheral nerves
      and nerve roots of the spinal cord we also found a positive staining of Schwann
      cells and some axons. These immunoreactions could be confirmed by Western blot
      analyses. Next we analysed postmortem paraffin sections of the spinal cord of
      seven patients suffering from ALS (age range 30-76 years, female/male = 4:3). We
      found CNTF immunoreactivity in most of the motor neurons of the ventral horn in 5
      cases. In two cases the number of positively stained motor neurons was less. From
      these results we conclude that CNTF is expressed in a high number of upper and
      lower motor neurons in the human CNS and that its expression is maintained in ALS
      patients.

PMID- 8866437
TI  - Bilateral perioral sensory symptom after unilateral stroke: does it have a
      localizing value?
AB  - Bilateral perioral sensory dysfunction due to unilateral cerebral lesion is rare,
      and has been thought to be caused by midline brainstem lesions. Six patients are
      described herewith, with bilateral perioral sensory symptoms due to unilateral
      strokes that do not involve the mid-brainstem region. Brain-computed tomographic
      scan and magnetic resonance imaging demonstrated unilateral cerebral strokes in
      the thalamus, posterior limb of the internal capsule, basal ganglia, fronto
      parietal cortex and the insular-frontal subcortical area. This observation
      suggests that bilateral perioral sensory symptoms do not have a localizing value.
      Possible pathogenetic mechanisms for this sign are discussed.

PMID- 8866438
TI  - Acanthocytosis, retinitis pigmentosa, pallidal degeneration. Report of two cases
      without serum lipid abnormalities.
AB  - We describe two unrelated patients with Hallervorden-Spatz, disease characterized
      by prominent facio-bucco-lingual dyskinesia. Acanthocytosis and retinitis
      pigmentosa were additional findings. Brain MRI showed the typical 'tiger's eye'
      image of the globus pallidus. This phenotype closely resembled the so-called HARP
      syndrome (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and
      pallidal degeneration), but extensive serum lipid study failed to demonstrate any
      lipoprotein abnormality. Our results raise the question whether HARP syndrome is
      an autonomous entity or a particular phenotype of Hallervorden-Spatz disease.

PMID- 8866439
TI  - Asymptomatic familial hyperCKemia associated with desmin accumulation in skeletal
      muscle.
AB  - We describe a family, two brothers and their mother, who came to our observation
      because of slight to moderate hyperCKemia. The younger brother, who had the
      highest CK values, was only suffering from episodic myalgia, the other two
      members of the family were asymptomatic. Neurological examination was normal.
      Both brothers underwent muscle biopsy which was significant for the presence of
      abnormal sarcoplasmic areas of desmin accumulation. So far, desmin abnormalities
      have never been reported in patients with such a mild neuromuscular pattern. We
      discuss possible correlations between severity of clinical phenotype and degree
      of desmin accumulation.

PMID- 8866440
TI  - High cervical myelopathy presenting with the numb clumsy hand syndrome.
AB  - We report two patients with numb clumsy hands due to cervical spondylotic spinal
      cord compression. It is proposed that arterial insufficiency in the watershed
      area between the central and radial arterial systems of the cervical cord
      explains the sensory findings in the upper extremities with preservation of motor
      function. Although this is a rare conditions, its recognition is important since
      the prognosis is improved by early surgical decompression.

PMID- 8866441
TI  - Piperacillin-induced encephalopathy.

PMID- 8866442
TI  - Doppler sonographic resistive index in obstructed kidneys.
AB  - Doppler sonographic findings were correlated with symptoms and intravenous
      urographic findings in 31 patients with unilateral renal obstruction and in 30
      control subjects. No significant correlation was found between resistive index
      and symptom duration or between resistive index and pelvicalyceal opacification
      time on intravenous urography. With a cutoff resistive index of 0.7, the
      sensitivity was 19.3% in diagnosing unilateral obstruction; however, it was 80%
      in the subgroup with acute symptoms and severely delayed pelvicalyceal
      opacification time. Doppler sonography has very low sensitivity in diagnosing
      unilateral renal obstruction, but it may be useful when the obstruction is acute
      and severe.

PMID- 8866443
TI  - Medial collateral ligament injuries of the knee: ultrasonographic findings.
AB  - The aims of our study were (1) to describe the ultrasonographic findings of the
      injured medial collateral ligament of the knee and (2) to assess the usefulness
      of ultrasonography in both evaluating the presence and location of the medial
      collateral ligament injuries and predicting the prognoses for the patients. The
      study group consisted of 16 patients with the clinical diagnosis of medial
      collateral ligament injury. We also examined 20 knee joints in 10 volunteers who
      had no history of injury to the knee. To predict prognoses, we divided the
      patients into two groups on the basis of the location of medial collateral
      ligament injuries. A thickened and heterogeneously hypoechoic appearance of the
      medial collateral ligament was considered abnormal. The normal medial collateral
      ligament was a thin and moderately homogeneous hypoechoic band with an average
      thickness of 4.3 mm (range, 3.3 to 5.6 mm) at the femoral attachment and of 2.3
      mm (range, 1.3 to 3.2 mm) at the tibial attachment. All injured medial collateral
      ligament structures were thickened and heterogeneously hypoechoic. According to
      the criteria for grading of medial collateral ligament injury with stress view,
      10 patients had grade III medial collateral ligament tears, three had grade II
      tears, and none had grade I injuries. In 15 (94%) of 19 knees, a correct
      diagnosis could be made with ultrasonography. Ultrasonography is useful in
      evaluating isolated medial collateral ligament injuries and in predicting patient
      outcome on the basis of the location of the medial collateral ligament injuries.

PMID- 8866444
TI  - In vivo three-dimensional sonographic measurement of organ volume: validation in
      the urinary bladder.
AB  - The purpose of this study was to assess the accuracy of in vivo measurement of
      organ volume using 3DUS and compare the results to 2D sonographic methods using
      the urinary bladder as the target organ and voided urine volume for validation.
      Fifty normal volunteers were studied. 2D volume measurements were based on
      length, width, and depth data and assumed a regular geometric model. 3D volume
      measurements were based on masked slices with the voxels integrated over the
      entire bladder. Voided urine volumes ranged from 35 ml to 701 ml. Residual urine
      volume was present in 48% of the subjects and ranged from 1% to 14% of the voided
      volume. 2D volume estimates for all 50 subjects had a mean absolute value of the
      error of 27.5% +/- 17.8%. 3D volume measurements had a mean absolute value of the
      error of 4.3% +/- 3.7% (transverse) and 5.6% +/- 3.8% (longitudinal). 3DUS
      provided more accurate volume measurements than 2DUS, particularly for
      irregularly shaped organs.

PMID- 8866445
TI  - Relationship of uterine perfusion to outcome of intrauterine insemination.
AB  - This prospective study was undertaken to evaluate the prognostic value of uterine
      perfusion on the day of human chorionic gonadotropin administration in patients
      who were undergoing intrauterine insemination. Uterine perfusion was evaluated by
      measuring the pulsatility index of the ascending branch of the uterine arteries
      on the day of administration of human chorionic gonadotropin. No pregnancy
      occurred when the pulsatility index of the ascending branch of the uterine
      arteries was more than 3. The fecundity rate was 18% when the pulsatility index
      was less than 2 and was 19.8% when the pulsatility index was between 2 and 3 (not
      significant). The continuing pregnancy rate was 18% when the pulsatility index
      was less than 2, compared with 12.1% when the pulsatility index was between 2 and
      3 (P < 0.05). Our data suggest that the measurement of uterine perfusion on the
      day of human chorionic gonadotropin administration may have predictive value
      regarding fecundity and the continuation of pregnancy in intrauterine
      insemination.

PMID- 8866446
TI  - Role of high frequency ultrasonography in the evaluation of palpable breast
      masses in Chinese women: alternative to mammography?
AB  - We prospectively assessed the accuracy of high resolution breast ultrasonography
      in the diagnosis of palpable breast masses in comparison to clinical palpation
      and x-ray mammography. Four hundred and eight Chinese women with palpable breast
      lumps had clinical assessment followed by ultrasonography of the breast,
      mammography (for women over 35 years), and fine needle aspiration cytology.
      Excisional biopsy or surgery was performed for suggestive lesions. The clinical,
      mammographic and ultrasound diagnoses were compared with the final pathologic
      diagnosis. In the determination of whether a lesion was malignant, the
      sensitivity, specificity, and positive predictive values were 97%, 97%, and 85%,
      respectively, for ultrasonography; 92%, 94%, and 84%, respectively, for
      mammography; and 88%, 92%, and 67%, respectively, for clinical evaluation. The
      specificity for combined clinical palpation and ultrasonography was higher (99%)
      than that for combined clinical palpation and mammography (96%). Addition of
      ultrasonography to combined clinical palpation and mammography increased
      specificity. Mammography in addition to combined clinical palpation and
      ultrasonography did not significantly improve the sensitivity, specificity, or
      positive predictive value. This limited usefulness raises the question as to
      whether it should be eliminated in the workup of a palpable mass in the average
      Chinese patient. Its main advantage is the detection of extended foci of
      carcinoma in situ related to a palpable mass, which often is undetected by
      ultrasonography.

PMID- 8866447
TI  - Corpus luteum blood flow in abnormal early pregnancy.
AB  - Thirty-eight consecutive patients with the diagnosis of abnormal early singleton
      pregnancy were studied with transvaginal color velocity imaging and pulsed
      Doppler ultrasonography to assess corpus luteum blood flow. Mean gestational age
      was 8.5 weeks (range, 6 to 12 weeks). Patients' mean age was 30.9 years (range,
      24 to 43 years). There were 19 (50%) threatened abortions, 13 (34.2%) missed
      abortions, and six (15.8%) anembryonic pregnancies. Blood flow impedance in the
      corpus luteum was estimated by calculating the resistive index. The results of
      this study group were compared with those obtained in a series of 85 normal
      singleton early pregnancies used as controls. Overall, detection of corpus luteum
      blood flow was 78.9% in study group and 76.4% in control group (P = 0.51). Mean
      resistive index +/- standard deviation in the control group was 0.50 +/- 0.10;
      the corresponding values in threatened abortion, anembryonic pregnancy, and
      missed abortion were 0.52 +/- 0.10, 0.42 +/- 0.06, and 0.57 +/- 0.05,
      respectively. No statistical. differences in mean resistive index were found
      among threatened abortion and anembryonic pregnancy with respect to control
      group. A higher mean resistive index was observed in missed abortion than in
      control group (P < 0.01). In conclusion, our data show that luteal
      vascularization might be decreased in missed abortion but not in threatened
      abortion and anembryonic pregnancy.

PMID- 8866448
TI  - Development of severe aortic stenosis and left ventricular dysfunction with
      endocardial fibroelastosis in a second trimester fetus.

PMID- 8866449
TI  - Development of significant left and right ventricular hypoplasia in the second
      and third trimester fetus.

PMID- 8866450
TI  - Nerve territory-oriented macrodactyly: unusual cause of carpal tunnel syndrome.

PMID- 8866451
TI  - Craniofacial damage from amniotic band syndrome subsequent to pathologic
      chorioamniotic separation at 10 weeks' gestation.

PMID- 8866452
TI  - Cardiorespiratory, endocrine and metabolic changes in ponies undergoing
      intravenous or inhalation anaesthesia.
AB  - Six Welsh gelding ponies (weight 246 +/- 6 kg) were premedicated with 0.03 mg/kg
      of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v.
      Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and
      lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2
      h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1
      month later using the same induction regime and anaesthesia was maintained with a
      combination of detomidine, ketamine and guaiphenesin, while the ponies breathed
      oxygen-enriched air. Electrocardiogram, heart rate, mean arterial blood pressure,
      cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose,
      lactate and cortisol were measured and cardiac index and systemic vascular
      resistance were calculated in both groups. Beta-endorphin, met-enkephalin,
      dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and
      catecholamines were measured in the halothane anaesthesia group only and 11
      deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory
      depression was more marked during halothane anaesthesia. Hyperglycaemia developed
      in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol
      increased during halothane and decreased during TIVA. There were no changes in
      the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA
      produced better cardiorespiratory performance and suppressed the endocrine stress
      response observed during halothane anaesthesia.

PMID- 8866453
TI  - Haemodynamic, electrocardiographic, electrophysiologic and pharmacokinetic
      activity of 4'-hydroxypropranolol in dogs.
AB  - We determined the haemodynamic, electrocardiographic and electrophysiologic
      effects, and the pharmacokinetic properties of 4'-hydroxypropranolol (4'-OHP) by
      conducting three different experiments in dogs. In experiment 1 the plasma
      concentrations of 4'-OHP (mg/kg, i.v.) in pentobarbital anaesthetized dogs were
      determined by HPLC and pharmacokinetic parameter values were estimated. The
      terminal elimination half-life (t1/2) for 4'-OHP was 69.4 min, the apparent
      volume of distribution (Vd) was 3.39 L/kg and the total clearance (Clt) was 53.6
      mL/min.kg. These data were subsequently used to calculate the loading and
      maintenance doses of 4'-OHP required to produce targeted steady-state plasma
      concentrations for 4'-OHP of 30, 60, 120, 240 and 480 ng/mL. In experiment 2 the
      haemodynamic and electrocardiographic effects for target plasma concentrations of
      4'-OHP were determined in two groups of pentobarbital anaesthetized dogs, and
      beta-blocking activity was assessed by infusion or bolus doses of isoproterenol.
      The haemodynamic and electrocardiographic effects of the target plasma
      concentrations (30, 60, 120 ng/mL) of 4'-OHP were first determined in seven
      pentobarbital anaesthetized dogs (Group 1). Beta blocking activity was assessed
      by the infusion of 0.1 microgram/kg/min isoproterenol. The infusion of 4'-OHP
      produced dose dependent decreases in heart rate, cardiac output, dP/dtmax, mean
      arterial pressure and left ventricular diastolic pressure. The PR interval of the
      lead II electrocardiogram increased and the QTc interval decreased. These
      haemodynamic and electrocardiographic changes became apparent at plasma 4'-OHP
      concentrations equal to or greater than 30 ng/mL. Plasma concentrations of 4'-OHP
      equal to or greater than 30 ng/mL prevented the haemodynamic and
      electrocardiographic effects of isoproterenol infusion. In group 2 dogs, (seven
      dogs) the haemodynamic and electrocardiographic effects of target plasma
      concentrations (30, 60, 120, 240, 480 ng/mL) of 4'-OHP were evaluated and beta
      blocking activity was assessed by the i.v. bolus administration of 1 and 4
      micrograms/kg of isoproterenol. The infusion of 4'-OHP produced haemodynamic and
      electrocardiographic changes similar to those in group 1 dogs. In addition, the
      QRS duration of the electrocardiogram increased at plasma concentrations of 4'
      OHP equal to or greater than 240 ng/ mL. The haemodynamic and
      electrocardiographic effects of i.v. bolus dose administrations of 1 and 4
      micrograms/kg isoproterenol were abolished by plasma concentrations of 4'-OHP
      equal to or greater than 240 ng/mL. In experiment 3 we determined the
      electrophysiologic effects of 10(-9) to 10(-5) mmol/L 4'-OHP on Tyrodes
      superfused bundles of canine Purkinje fibres. Action potential duration and the
      effective refractory period decreased at superfusate concentrations of 4'-OHP
      equal to or greater than 10(-7) mmol/L. Action potential overshoot, action
      potential total amplitude, the rate of rise of phase 0 (dV/dt) and spontaneous
      rate decreased at superfusage concentrations of 4'-OHP equal to or greater than
      800 ng/mL. These studies demonstrate that: 1) 4'-OHP produces haemodynamic.
      electrocardiographic and electrophysiologic effects similar to those of other
      beta-blocking drugs in pentobarbital anaesthetized dogs; 2) the haemodynamic and
      electrocardiographic effects produced by 4'-OHP are apparent at relatively low
      plasma concentrations (30 ng/mL); 3) the concentrations of 4'-OHP that are
      required to produce direct cardiac electrophysiologic effects are unlikely to be
      responsible for clinical antiarrhythmic activity and 4) 4'-OHP blocks the
      haemodynamic and electrocardiographic effects of infusions and i.v. bolus
      administration of isoproterenol.

PMID- 8866454
TI  - Pharmacokinetics of epidural butorphanol in isoflurane-anaesthetized dogs.
AB  - Sixteen healthy male dogs were used at random in this protocol. The dogs were
      anaesthetized with isoflurane in oxygen. Eight of the dogs received 0.25 mg/kg of
      butorphanol (group B) and the others an equal volume of isotonic saline (group S)
      administered by a catheter inserted in the lumbosacral epidural space.
      Butorphanol concentrations in plasma and cerebrospinal fluid (CSF) were measured
      using high-performance liquid chromatography with electrochemical detection.
      Maximum concentration of butorphanol and time to obtain this concentration were
      42.28 ng/mL at 13.88 min in blood, and 18.03 ng/mL at 30 min in CSF. Volume of
      distribution, clearance, mean distribution and elimination half-lives were
      respectively 4.39 L/kg, 2.02 L/h.kg, 16.5 min and 189.1 min. Mean isoflurane
      minimal alveolar concentration values for group B obtained following hind- or
      forelimb stimulation decreased by 31% after epidural butorphanol. Cutaneous
      analgesia (to pin-prick test) persisted for 3 h after the end of isoflurane
      anaesthesia in group B and was in correlation with the plasmatic analgesic dose
      of butorphanol (9 ng/mL). These results suggested that analgesia was
      predominantly obtained by action of butorphanol on the supraspinal structures
      following its vascular systemic absorption.

PMID- 8866455
TI  - Pharmacokinetics and bioavailability of doxycycline in turkeys.
AB  - The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3-,
      6- and 12-week-old fasted turkeys, after a single intravenous (i.v.) dose of 25
      mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two
      compartment model. The mean (+/-SD) elimination half-life was 10.6 +/- 0.7, 10.8
      +/- 1.5, 7.9 +/- 1.4 and 10.0 +/- 0.9 h in 3 day, 3-, 6- and 12-week-old turkeys,
      respectively. Mean (+/- SD) total body clearance was 0.19 (+/-0.01), 0.27 (+/
      0.03), 0.11 (+/-0.03) and 0.06 (+/-0.01) L/h.kg in 3 day, 3-, 6- and 12-week-old
      turkeys, respectively. The steady-state volume of distribution was 1.77 (+/-0.2),
      2.1 (+/-0.2), 0.7 (+/-0.4) and 0.5 (+/-0.2) L/kg in turkeys of the above
      mentioned ages, respectively. The AUC value significantly increased with the age
      of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body
      weight was administered to 3 day. 3-, 6- and 12-week-old turkeys. The maximal
      plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 micrograms/mL.
      with tmax values of 4.7, 1.5, 2.8 and 5.4 h, for the different ages,
      respectively. In fed turkeys the Cmax values were 2.5, 6.1, 4.8 and 3.0
      micrograms/mL. with tmax values of 4.2, 5.3, 4.5 and 7.5 h, respectively. The
      absolute bioavailability in fasted turkeys varied between 25.0 +/- 9.0% (for 12
      week-old birds) and 63.5 +/- 7.1% (for 3-week-old birds). The relative
      bioavailability varied between 40.0 +/- 13.0% (for 12-week-old birds) and 83.7 +/
      14.3% (for 3-week-old birds).

PMID- 8866456
TI  - In vitro and in vivo binding of trimethoprim and sulphachlorpyridazine to equine
      food and digesta and their stability in caecal contents.
AB  - Binding of antibiotics to food has received little attention in equine medicine,
      although such binding could potentially reduce the bioavailability and clinical
      efficacy. In the present study, binding of trimethoprim (TMP) and
      sulphachlorpyridazine (SCP) to hay, grass silage and concentrate was investigated
      in vitro in buffer at pH 6.8 at different concentrations. The binding of TMP and
      SCP to caecal contents was also studied. In addition, the degradation of TMP and
      SCP by the caecal microflora was investigated by incubating sterilized and non
      sterilized caecal contents for 3 h at 37 degrees C under anaerobic conditions and
      comparing the TMP and SCP contents. Further, a TMP/SCP powder formulation was
      adminstered orally with concentrate at a dose rate of 5 mg/kg TMP and 25 mg/kg
      SCP to three ponies with a caecum fistula; the animals were deprived of food for
      8 h before administration. Blood samples, caecal contents samples and faecal
      samples were collected and analysed for TMP and SCP concentrations by means of
      high performance liquid chromatography (HPLC). Three non-fistulated ponies,
      acting as control animals, were fed the same dose of TMP/SCP with concentrate
      after 8 h of food deprivation and blood samples were taken. The percentage of in
      vitro binding of TMP as well as SCP to hay, grass silage and concentrate at
      concentrations of 4 micrograms/mL to 10 micrograms/mL was high (60-90%). TMP and
      SCP were also extensively bound to caecal contents (50-70%). At spiking
      concentrations above 10 micrograms/mL the percentage of binding decreased. There
      was no evidence of biodegradation of TMP or SCP in caecal contents. In vivo, both
      drugs could be detected in the caecal contents and in the faeces of three
      fistulated ponies. However, the fistulated ponies differed from the control
      ponies in that their TMP and SCP plasma concentrations were higher, and two
      fistulated ponies did not show double peaks in their plasma concentration-time
      curves. Therefore, the fistulated ponies did not provide an optimal model for in
      vivo binding studies. Despite this limitation, it can be concluded that binding
      of TMP and SCP to food is a major cause of the limited bioavailability of these
      drugs in the horse. It is hypothesized that the binding is reversible, and that a
      second absorption phase occurs in the large intestine, but part of the
      administered dose remains bound as both drugs were found in the faeces.

PMID- 8866457
TI  - The bioavailability of febantel in dehydrated camels.
AB  - In the present study the bioavailability of febantel paste and febantel
      suspension was investigated in the fully hydrated and the dehydrated camel. The
      serum concentrations of febantel and its metabolites, fenbendazole, oxfendazole
      and fenbendazole sulfone were determined by high performance liquid
      chromatography following extraction with ether. The exposure to febantel and its
      metabolites in fully hydrated camels was significantly higher in camels dosed
      with febantel paste compared to febantel suspension, as measured by AUC and Cmax.
      The AUC and Cmax of fenbendazole and oxfendazole were significantly lower in
      dehydrated camels as compared to control camels dosed with febantel paste. The
      systemic availability of febantel suspension in control and dehydrated camels was
      very low and differences between dehydration and control phases were
      insignificant. The low systemic availability of febantel in camels dosed with
      febantel suspension may cause nematodes to become resistant to this anthelmintic.
      It is, thus, suggested to increase the dose of febantel paste in dehydrated
      camels in order to increase the exposure to febantel and its metabolites. The
      binding of febantel, fenbendazole, oxfendazole and fenbendazole sulfone to
      camels' serum proteins was over 85%. Oxfendazole was only about 70% bound.
      Dehydration of 10 days did not affect the binding of these benzimidazole
      derivatives to serum proteins.

PMID- 8866458
TI  - Stability of ivermectin in rumen fluids.
AB  - To determine whether ivermectin is metabolized in the rumen, in vitro studies
      were conducted with the tritium-labelled H2B1a component of ivermectin in rumen
      fluid from sheep and cattle. No detectable metabolism occurred over 24 h in in
      vitro incubations at 38 degrees C. The viability of the microbes in the rumen
      fluids was demonstrated by the conversion of 17% and 11% of [14C]cellulose to
      14CO2 in 24 h in the incubations with sheep and steer rumen fluids respectively.
      The results indicate that ivermectin is not metabolized in the rumen. Based on
      the lack of in vitro metabolism of ivermectin in rumen fluid, the similarity of
      in vitro liver microsomal metabolism with in vivo metabolism of the avermectins
      and the physicochemical properties of the avermectins, any disappearance of
      ivermectin in vitro from rumen fluid is probably a result of binding to solids or
      surfaces. Apparent discrimination by dung beetles, where observed, between
      control faeces and faeces from cattle or sheep treated with ivermectin or
      abamectin therefore must be attributable to chance, to factors unrelated to
      treatment or to factors such as changes in amino acid composition rather than the
      production of volatile metabolites of ivermectin.

PMID- 8866459
TI  - Relative bioavailability of microgranulated sulfadimidine in veal calves.
AB  - The kinetics of free and microgranulated sulfadimidine were compared in milk-fed
      calves dosed orally (180 mg/kg) in a crossover study. Microgranulation results in
      delayed absorption of sulfadimidine and poor bioavailability, with the area under
      the plasma concentration-time curve (AUC(0-infinity)) reduced from 7400 to 3781
      micrograms.h/mL, and maximum plasma concentration (Cmax) reduced from 188.1 +/-
      39.0 to 84.41 +/- 22.6 micrograms/mL. It is concluded that sulfadimidine
      microgranulated with long chain fatty acids is not suitable for use in milk-fed
      calves; the gastrointestinal transit time is too rapid to allow full release of
      the drug, markedly limiting its bioavailability. In adult animals, or in the
      young of other animal species in which digesta transit time is slower than in
      calves, the bioavailability of microgranulated sulfadimidine may be much greater.

PMID- 8866460
TI  - Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral
      administration to fed and fasted pigs.
AB  - The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline
      (CTC) was measured after intravenous and oral administration to pigs. Eighteen
      healthy pigs (six for each compound) weighing 22-43 kg received a dose of 10
      mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a
      fasted and a fed condition in a three-way crossover design. The three
      tetracyclines were present in plasma up to 30 hours after intravenous and after
      oral administration to fasted as well as fed pigs. The volume of distribution was
      1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The
      bioavailability was in general low for all the three tetracyclines. The presence
      of food did not affect the bioavailability of OTC, which was only 3% in both
      fasted and fed pigs. For TC there was a significantly higher bioavailability in
      fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not
      significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of
      food affected the bioavailability only for TC, it prolonged the absorption phase
      for all three tetracyclines. Based on the bioavailability and the resulting
      plasma concentrations, it is concluded that it is not possible to obtain a
      therapeutically active concentration in plasma or tissues after oral
      administration of any of the three tetracyclines to fed or fasted pigs.

PMID- 8866461
TI  - The safety assessment of drug residues at injection sites.

PMID- 8866462
TI  - Analysis of amoxycillin in bustard plasma by high-performance liquid
      chromatography after administration of a long-acting formulation.

PMID- 8866463
TI  - Disposition of single-dose oral enrofloxacin in the horse.

PMID- 8866464
TI  - Influence of carprofen on minimum alveolar concentration of halothane in dogs.

PMID- 8866465
TI  - Metabolism and pharmacokinetics of albendazole after oral administration to
      chickens.

PMID- 8866466
TI  - Plasma analysis and pharmacokinetics of zaltidine, an H2-antagonist, in cattle
      after intravenous, intramuscular, subcutaneous, and oral administration.

PMID- 8866467
TI  - Questions about gonococcal pilus phase- and antigenic variation.
AB  - Pathogenic organisms inhabit one of several defined locations within a host where
      temperature, pH, and nutrients are relatively constant. While the microorganism
      must adapt to different environments within the host, the host immune system is
      the most formidable predator that can limit the growth of a pathogen. Neisseria
      gonorrhoeae (the gonococcus, Gc) is the causative agent of gonorrhoea, and has
      evolved several systems for varying the antigenicity of different surface
      antigens, presumably to help evade the effects of the human immune system. The
      On/Off/On phase variation of surface structure expression also alters the
      antigenic characteristics of the bacterial cell surface. Antigenic variation of
      the major subunit of the pilus, pilin, occurs by unidirectional, homologous
      recombination between a silent locus and the expression locus. The silent loci
      lie from 1 to 900 kb from the expression locus in the chromosome yet all can
      donate their sequences to the expression locus. The genetic composition of the
      pilin loci of two Gc strains has been elucidated, and the types of changes that
      lead to altered forms of the pilus have been extensively characterized. However,
      little is known about the precise molecular mechanisms used to allow high
      frequency, non-reciprocal, chromosomal recombination between pilin loci or about
      what regulates the process of maintaining chromosome fidelity.

PMID- 8866469
TI  - Genetic analysis of the transcriptional arrangement of Azotobacter vinelandii
      alginate biosynthetic genes: identification of two independent promoters.
AB  - The study of alginate biosynthesis, the exopolysaccharide produced by Azotobacter
      vinelandii and Pseudomonas aeruginosa, might lead to different biotechnological
      applications. Here we report the cloning of A. vinelandii algA, the gene coding
      for the bifunctional enzyme phosphomannose isomerase-guanosine diphospho-o
      mannose pyrophosphorylase (PMI-GMP). This gene was selected by the
      complementation for xanthan gum production of Xanthomonas campestris pv.
      campestris xanB-mutants, which lack this enzymatic activity. The complementing
      cosmid clones selected, besides containing algA, presented a gene coding for an
      alginate lyase activity (algL), and some of them also contained algD which codes
      for GDP-mannose dehydrogenase. We present here the characterization of the A.
      vinelandii chromosomal region comprising algD and its promoter region, algA and
      algL, showing that, as previously reported for P. aeruginosa, A. vinelandii has a
      cluster of the biosynthetic alginate genes. We provide evidence for the presence
      of an algD-independent promoter in this region which transcribes at least algL
      and algA, and which is regulated in a manner that differs from that of the algD
      promoter.

PMID- 8866468
TI  - Overlaps and parallels in the regulation of intrinsic multiple-antibiotic
      resistance in Escherichia coli.
AB  - Chromosomally encoded systems present in a variety of bacteria appear to play a
      central role in determining the Intrinsic level of resistance to many commonly
      used antibiotics. Work with the Gram-negative bacterium Escherichia coli has
      shown that there is significant similarity at the amino acid sequence level among
      the structural components of these resistance systems as well as among their
      genetic regulators. This review describes two of the better-studied regulatory
      systems, marRAB and soxRS, as well as two regulated multidrug-efflux systems,
      encoded by emrAB and acrAB, and focuses on conserved themes in their primary
      structures and environmental stimuli. The observed resistance to clinically
      important antibiotics appears to reflect an overlap with broad-ranged adaptive
      responses by free-living bacteria to noxious plant materials in their natural
      environment.

PMID- 8866470
TI  - Protein secretion by heterologous bacterial ABC-transporters: the C-terminus
      secretion signal of the secreted protein confers high recognition specificity.
AB  - Pseudomonas aeruginosa releases several extracellular proteins which are secreted
      via two independent secretion pathways. Alkaline protease (AprA) Is released by
      its own specific secretion machinery which is an ABC-transporter. Despite
      sequence similarities between components of ABC-transporters in different
      bacteria, each transporter is dedicated to the secretion of a particular protein
      or a family of closely related proteins. Heterologous complementation between ABC
      transporters for unrelated polypeptides can occur, but only at a very low level.
      We show that the 50 C-terminal amino acids of AprA constitute an autonomous
      secretion signal. By heterologous complementation experiments between the
      unrelated alpha-haemolysin (HlyA) and Apr secretion systems we demonstrated that
      it is only the recognition of the secretion signal by the translocator which
      confers specificity to the secretion process. Secretion was size-dependent.
      However inclusion of glycine-rich repeats from HlyA in AprA seems to overcome the
      size limitation exerted by the Apr secretion apparatus such that the machinery
      secreted a hybrid protein 20 kDa larger than the normal maximal size.

PMID- 8866471
TI  - Competence pheromone, oligopeptide permease, and induction of competence in
      Streptococcus pneumoniae.
AB  - An unmodified heptadecapeptide pheromone capable of eliciting competence for
      genetic transformation in Streptococcus pneumoniae has recently been identified
      and characterized. In considering possible signal-transduction mechanisms for the
      peptide, the previously characterized Ami oligopeptide permease and the three
      highly homologous oligopeptide-binding lipo-proteins. AmiA, AliA, and AliB,
      appeared to be good candidates for receptors. We therefore compared the
      spontaneous transformability of Ami, AliA and AliB mutants to that of an isogenic
      wild-type strain and we investigated the response of the various mutants to
      treatment with synthetic competence-stimulating peptide (CSP). Our results
      clearly demonstrate that neither Ami nor any of the three highly homologous
      oligopeptide-binding lipoproteins identified so far in S. pneumoniae are required
      for competence induction following treatment with synthetic CSP. Although the
      existence of a fourth unidentified oligopeptide-binding lipoprotein and/or a
      second oligopeptide permease operon could not be completely ruled out, we favour
      the hypothesis that CSP signal transmission rather involves a two-component
      regulatory system. Although none of the single or double Ami and All mutants
      tested appeared severely affected for competence, an exceptional aliB plasmid
      insertion mutation abolished competence completely. In addition, the triple AmiA
      AliA-AliB mutant differed from wild type in showing no sharp peak of competence
      but exhibiting transformability throughout the exponential phase of growth. These
      and previous observations are discussed and a general hypothesis is proposed to
      account for the modulation of competence by peptide permease mutants in S.
      pneumoniae.

PMID- 8866472
TI  - Intracellular endosymbiotic bacteria of Camponotus species (carpenter ants):
      systematics, evolution and ultrastructural characterization.
AB  - Intracellular endosymbiotic bacteria inherent to ants of the genus Camponotus
      were characterized. The bacteria were localized in bacteriocytes, which are
      specialized cells of both workers and queen ants; these cells are intercalated
      between epithelial cells of the midgut. The bacteriocytes show a different
      morphology from the normal epithelial cells and carry a large number of the rod
      shaped Gram-negative bacteria free in the cytoplasm. The bacteria were never
      observed in the neighbouring epithelial cells, but they were found
      intracellularly in oocytes, strongly indicating a maternal transmission of the
      bacteria. The 16S DNA encoding rrs loci of the endosymbionts of four species of
      the genus Camponotus derived either from Germany (C. herculeanus and C.
      ligniperdus), North America (C. floridanus) or South America (C. rufipes) were
      cloned after polymerase chain reaction (PCR) amplification using oligonucleotides
      complementary to all so far known eubacterial rrs sequences. The DNA sequences of
      the rrs loci of the four endosymbionts were determined, and, using various genus-
      and species-specific oligonucleotides derived from variable regions in the rrs
      sequences, the identity of the bacteria present in the bacteriocytes and the
      ovarian cells was confirmed by PCR and in situ hybridization techniques.
      Comparison of the 16S DNA sequences with the available database showed the
      endosymbiotic bacteria to be members of the gamma-subclass of Proteobacteria.
      They formed a distinct taxonomic group, a sister taxon of the taxons defined by
      the tsetse fly and aphid endosymbionts. Within the gamma-subclass, the cluster of
      the ant, tsetse fly and aphid endosymbionts are placed adjacent to the family of
      Enterobacteriaceae. The evolutionary tree of the ant endosymbionts reflects the
      systematic classification and geographical distribution of their host insects,
      indicating an early co-evolution of the symbiotic partners and a vertical
      transmission of the bacteria.

PMID- 8866473
TI  - In vivo immobilization of enzymatically active polypeptides on the cell surface
      of Staphylococcus carnosus.
AB  - Many surface proteins of Gram-positive bacteria are covalently anchored to the
      cell wall by a ubiquitous mechanism, involving a specific, C-terminal sorting
      signal. To achieve cell-wall immobilization of a normally secreted enzyme in
      vivo, we constructed a hybrid protein consisting of Staphylococcus hyicus lipase
      and the C-terminal region of Staphylococcus aureus fibronectin binding protein B
      (FnBPB). This region comprised the authentic cell-wall-spanning region and cell
      wall sorting signal of FnBPB. Expression of the hybrid protein in Staphylococcus
      carnosus resulted in efficient cell-wall anchoring of enzymatically active
      lipase. The cell-wall-immobilized lipase (approximately 10,000 molecules per
      cell) retained more than 80% of the specific activity, compared to the C
      terminally unmodified S. hyicus lipase secreted by S.carnosus cells. After
      releasing the hybrid protein from the cell wall by lysostaphin treatment. Its
      specific activity was indistinguishable from that of the unmodified lipase. Thus,
      the C-terminal region of FnBPB per se was fully compatible with folding of the
      lipase to an active conformation. To study the Influence of the distance between
      the cell-wall sorting signal and the C-terminus of the lipase on the activity of
      the immobilized lipase, the length of this spacer region was varied. Reduction of
      the spacer length gradually reduced the activity of the surface-immobilized
      lipase. On the other hand, elongation of this spacer did not stimulate the
      activity of the immobilized lipase, indicating that the spacer must exceed a
      critical length of approx. 90 amino acids to allow efficient folding of the
      enzyme, which probably can only be achieved outside the peptidoglycan web of the
      cell wall. When the lipase was replaced by another enzyme, the Escherichia coli
      beta-lactamase, the resulting hybrid was also efficiently anchored in an active
      conformation to the cell wall of S. carnosus. These results demonstrate that it
      is possible to immobilize normality soluble enzymes on the cell wall of S.
      carnosus-without radically altering their catalytic activity-by fusing them to a
      cell-wall-immobilization unit, consisting of a suitable cell-wall-spanning region
      and a standard cell-wall sorting signal.

PMID- 8866474
TI  - The Bacillus subtilis soj-spo0J locus is required for a centromere-like function
      involved in prespore chromosome partitioning.
AB  - During sporulation in Bacillus subtilis a small prespore cell is formed by an
      asymmetric cell division. Pre-spore chromosome partitioning occurs by a
      specialised mechanism in which septation precedes chromosome movement. We show
      that the spo0J gene is needed to specify the orientation of the chromosome at the
      time of polar division and to impose directionality on the subsequent transport
      of the remainder of the chromosome through the septum. Both phenotypes may arise
      by disruption of a centromere-like apparatus that anchors the or/C region of the
      prespore chromosome in the pole of the cell.

PMID- 8866475
TI  - CheC and CheD interact to regulate methylation of Bacillus subtilis methyl
      accepting chemotaxis proteins.
AB  - In this study, we have demonstrated that two unique proteins in Bacillus subtilis
      chemotaxis, CheC and CheD, interact. We have shown this interaction both by using
      the yeast two-hybrid system and by precipitation of in vitro translated products
      using glutathione-S-transferase fusions and glutathione agarose beads. We have
      also shown that CheC inhibits B. subtilis CheR-mediated methylation of B.
      subtilis methyl-accepting chemotaxis proteins (MCPs) but not of Escherichia coli
      MCPs. It was previously reported that cheC mutants tend to swim smoothly and do
      not adapt to addition of attractant; cheD mutants have very poorly methylated
      MCPs and are very tumbly, similar to cheA mutants. We hypothesize that CheC
      exerts its effect on MCP methylation in B. subtilis by controlling the binding of
      CheD to the MCPs. In absence of CheD, the MCPs are poor substrates for CheR and
      appear to tie up, rather than activate, CheA. The regulation of CheD by CheC may
      be part of a unique adaptation system for chemotaxis in B. subtilis, whereby high
      levels of CheY-P brought about by attractant addition would allow CheC to
      interact with CheD and consequently leave the MCPs, reducing CheA activity and
      hence the levels of CheY-P.

PMID- 8866476
TI  - The role of the Saccharomyces cerevisiae CCC1 gene in the homeostasis of
      manganese ions.
AB  - We previously reported that oxidative damage in yeast lacking copper/zinc
      superoxide dismutase (SOD1) can be alleviated through mutations in PMR1, encoding
      a calcium P-type ATPase homologue that also functions in manganese homeostasis.
      In an attempt to further understand the relationship between manganese ions, PMR1
      and SOD1, we conducted a search for manganese homeostasis genes that interact
      with PMR1. A genomic library was screened for genes that, when overexpressed,
      suppress the manganese hypersensitivity associated with pmr1 mutations. A single
      clone was isolated that reduced manganese toxicity in both the pmr1 mutant and
      PMR1 wild-type yeast. This gene was identified as CCC1, previously shown to
      function in calcium metabolism. Our studies indicate that, like PMR1, CCC1
      functions in the homeostasis of both calcium and manganese ions. The Ccc1p
      polypeptide was found to localize to a Golgi-like organelle in yeast cells. Ccc1p
      co-fractionated with a Golgi marker in subcellular fractionation studies and,
      with immunofluorescence microscopy, Ccc1p exhibited a punctate pattern of
      staining typical of yeast Golgi. Our studies suggest that Ccc1p may act to
      sequester manganese ions in this organelle and limit the intracellular
      availability of the metal. First, overexpression of CCC1 reduced manganese
      cytotoxicity without lowering total accumulation of the metal. Second,
      overexpression of CCC1 appeared to limit the intracellular availability of the
      manganese ions needed to support aerobic growth of SOD1 mutants. We provide a
      model in which Ccc1p and Pmr1p work together to control the intracellular
      partitioning of manganese ions.

PMID- 8866477
TI  - Assembly proteins of CS1 pili of enterotoxigenic Escherichia coli.
AB  - Some strains of enterotoxigenic Escherichia coli associated with human diarrhoeal
      disease produce a class of pili represented by those called CS1. For the assembly
      of the major-pilin subunit, CooA, into pili, each of four linked genes, cooB, A,
      C, and D, is required. In this study, we have determined the subcellular
      localization of CooB, C and D, and investigated the molecular interactions of
      these proteins using specific antisera. CooD appears to be an integral pilus
      protein because it co-purifies with, and is strongly associated with, CS1 pili.
      In keeping with its role as an assembly protein, the CooD minor pilin (when
      overexpressed in CS1-piliated strains) was detected in periplasmic intermolecular
      complexes with the major-pilin subunit CooA. CooB is an assembly protein found
      exclusively in the periplasm of CS1-piliated strains. CooB also forms periplasmic
      intermolecular complexes with CooA, but does not constitute part of the final
      pilus structure. Immunoblot analysis of cell fractions showed that CooC is an
      outer membrane protein of CS1-piliated E. coli. Based on this information, we
      have proposed a model for CS1-pilus assembly which is very similar to the model
      for polymerization of the PapA pilin of uropathogenic E. coli. As the assembly
      proteins of Pap and CS1 pili are structurally unrelated, this may represent a
      case of convergent evolution.

PMID- 8866478
TI  - The use of differential display-PCR to isolate and characterize a Legionella
      pneumophila locus induced during the intracellular infection of macrophages.
AB  - The differential display (DD)-PCR technique has been modified to identify
      prokaryotic cDNA fragments that are differentially induced by facultative
      intracellular bacteria in response to the intracellular environment of eukaryotic
      cells. Several DD-PCR fragments identified from the intracellular bacterium
      Legionella pneumophila were induced at 4 h post-infection of the U937 macrophage
      like cells. From these, a 700 bp fragment was cloned and sequenced. Neither the
      DNA sequence nor the predicted protein sequence from the open reading frame has
      similarity to other sequences in genetic databases. Transcription of the
      chromosomal locus containing the 700 bp fragment (eml, for early stage macrophage
      induced locus) was induced by intracellular bacteria during the first few hours
      post-infection of macrophages but the expression was downregulated by 12 h post
      infection. Transcription of eml was not growth phase-related in vitro, and was
      not affected by in vitro stress stimuli. A 3.7 kb EcoRI genomic fragment
      containing the 700 bp DD-PCR product was cloned. Six mini-Tn 10 insertions in the
      3.7 kb EcoRI fragment were recombined into the L. pneumophila chromosome.
      Compared to the wild-type strain, five of the eml isogenic mutants had a similar
      phenotype of reduced cytopathicity to the U937 cells, showed a 100-fold increase
      in killing by macrophages during the first 5 h of the intracellular infection,
      and showed a 100-fold increase in killing during the first 24h of infection of
      the amoeba Hartmanella vermiformis. The 6th mutant had a phenotype
      indistinguishable from the wild-type strain. The cytopathicity defect of the
      mutants to the U937 cells was restored to wild-type levels by complementation of
      the mutants with a plasmid containing the 3.7 kb EcoRI fragment. These data
      showed that the 3.7 kb fragment containing eml is a novel L. pneumophila locus
      whose expression is uniquely induced by non-stress stimuli during early stages of
      the intracellular infection of phagocytic cells. Expression of this locus is
      required for survival of L. pneumophila within macrophages and within amoebae
      during early stages of the infection.

PMID- 8866479
TI  - Differential binding of BvgA to two classes of virulence genes of Bordetella
      pertussis directs promoter selectivity by RNA polymerase.
AB  - Transcription of virulence genes of Bordetella pertussis is co-ordinately
      regulated by the BvgA and BvgS proteins, which are members of the two-component
      family of bacterial signal-transduction proteins. BvgS is the transmembrane
      sensor and BvgA the transcriptional regulator. By gel mobility shift assays we
      demonstrate that phosphorylated BvgA (BvgA approximately P) forms distinct
      complexes with the filamentous haemagglutinin (PFHA) promoter DNA at different
      BvgA approximately P: DNA ratios. DNase I protection analyses show that
      phosphorylation of BvgA not only enhances affinity of the protein for the binding
      sites of the PFHA and bvgP1 promoters, but it extends significantly the bound
      region towards position -35 of these promoters. Conversely, a 10-fold higher
      amount of BvgA approximately P is required for binding to a large DNA region,
      from -168 to -60, of the pertussis toxin (Ptox) promoter sequence. These findings
      suggest that the molecular interaction of BvgA approximately P with the Ptox
      promoter is different from its interaction with the PFHA and bvgP1 promoters. The
      sigma 70 Escherichia coli RNA polymerase (RNP) does not bind to the bvg-regulated
      promoters. However, following the formation of a BvgA approximately P-promoter
      complex, the E. coli RNP specifically recognizes and binds to the bvg-regulated
      promoters. Thus, BvgA approximately P exerts its action at the level of promoter
      recognition by directing promoter selectivity by RNP.

PMID- 8866480
TI  - Internalin must be on the bacterial surface to mediate entry of Listeria
      monocytogenes into epithelial cells.
AB  - Entry of Listeria monocytogenes into cultured epithelial cells requires
      production of internalin, a protein with features characteristic of some Gram
      positive bacterial surface proteins, in particular an LPXTG motif preceding a
      hydrophobic sequence and a few basic residues at its C-terminal end. By
      immunofluorescence and immunogold labelling, we show that in wild-type L.
      monocytogenes, internalin is present on the cell surface and has a polarized
      distribution similar to that of ActA, another surface protein of L. monocytogenes
      involved in actin assembly. Through a genetic analysis, we establish that the C
      terminal region of internalin is necessary for cell-surface association, and that
      although internalin is partially released in the culture medium, its location on
      the bacterial surface is required to promote entry. Finally, using a 'domain
      swapping' strategy-replacement of the cell wall anchor of IniA by the membrane
      anchor of ActA- we show that the reduced ability to adhere and enter cells of
      strains expressing IniA-ActA correlates with a lower amount of surface-exposed
      internalin. Taken together, these results suggest that internalin exposed on the
      bacterial surface mediates direct contact between the bacterium and the host
      cell.

PMID- 8866481
TI  - The positions of the sigma-factor genes, whiG and sigF, in the hierarchy
      controlling the development of spore chains in the aerial hyphae of Streptomyces
      coelicolor A3(2).
AB  - whiG and sigF encode RNA polymerase sigma factors required for sporulation in the
      aerial hyphae of Streptomyces coelicolor. Their expression was analysed during
      colony development in wild-type and sporulation-defective whi mutant strains.
      Each gene was transcribed from a single promoter. Unexpectedly, whiG mRNA was
      present at all time points, including those taken prior to aerial mycelium
      formation; this suggests that whiG may be regulated post-transcriptionally.
      Transcription of whiG did not depend upon any of the six known 'early' whi genes
      required for sporulation septum formation (whiA, B, G, H, I and J), placing it at
      the top of the hierarchy of whi loci. sigF expression appeared to be regulated at
      the level of transcription; sigF transcripts were detected transiently when
      sporulation septa were observed in the aerial hyphae. Transcription of sigF
      depended upon all six of the early whi genes, including whiG. The sigF promoter
      does not resemble the consensus sequence established for sigma WhiG-dependent
      promoters and E sigma WhiG did not transcribe from the sigF promoter in vitro.
      Consequently, the genetic dependence of sigF upon whiG is very likely to be
      indirect. These results show that there is a hierarchical relationship between
      sigma factors required for Streptomyces sporulation and also that at least five
      other genes are involved in this transcriptional network.

PMID- 8866482
TI  - Examination of AsmA and its effect on the assembly of Escherichia coli outer
      membrane proteins.
AB  - asmA mutations were isolated as extragenic suppressors of an OmpF assembly
      mutant, OmpF315. This suppressor locus produced a protein that was present in
      extremely low levels and could only be visualized by Western blotting in cells
      where AsmA expression was induced from a plasmid. Detailed fractionation analyses
      showed that AsmA localized with the inner membrane. Curiously, however, the
      mutant OmpF assembly step influenced by AsmA occurred in the outer membrane,
      perhaps indicating an indirect involvement of AsmA in the assembly of outer
      membrane proteins. Biochemical examination of the outer membrane showed that asmA
      null mutations reduce lipopolysaccharide (LPS) levels, thereby lowering the
      ratios of glycerolphospholipids to LPS and envelope proteins to LPS in the outer
      membrane. Despite these quantitative alterations, no apparent structural changes
      in LPS or major phospholipids were noted. Reduced LPS levels in asmA mutants
      indicate a possible role of AsmA in LPS biogenesis. Data presented in this study
      suggest that asmA-mediated OmpF assembly suppression may have been achieved by
      altering the outer membrane fluidity, thus making it more amenable for the
      assembly of mutant proteins.

PMID- 8866483
TI  - Differential regulation of multiple overlapping promoters in flagellar class II
      operons in Escherichia coli.
AB  - The Escherichia coli flagellar operons are divided into three categories: classes
      I, II and III. Expression of class II depends on expression of class I. One of
      the class II gene products, the FIIA protein, is an alternative sigma factor
      (sigma 28) required for transcription of the class III operons. In this study, we
      have characterized, in vitro, a role of sigma 28 in the regulation of the class
      II operons. Among the three class II operons examined, the fliA and fliL operons,
      but not the flhB operon, could be transcribed by both sigma 70 RNA polymerase
      holoenzyme with FihD/C (E sigma 70-FlhD/C) and sigma 28 RNA polymerase holoenzyme
      (E sigma 28). The flhB operon could only be transcribed by E sigma 70-FlhD/C
      under the conditions used. Both the fliA and fliL operons contained two
      overlapping promoters oriented in tandem. The transcription of fliA directed by E
      sigma 28 could outcompete that by E sigma 70-FlhD/C, indicating a positive
      autoregulation. However, E sigma 28 could not displace E sigma 70-FlhD/C bound to
      the fliL promoter. The sigma 28-mediated positive regulation of the class II
      operons involved a mechanism in which sigma 28 competed with sigma 70 for core
      RNA polymerase. In addition, recruitment of core RNA polymerase from the sigma 70
      -10 site to the sigma 28 -10 was facilitated by formation of E sigma 70-FlhD/C
      pre-initiation complex. Taken together, the three class II promoters investigated
      are different in terms of their regulation by sigma 28. We propose that class II
      operons may be further divided into different subcategories.

PMID- 8866484
TI  - ERA, a novel cis-acting element required for autoregulation and ethanol
      repression of PDC1 transcription in Saccharomyces cerevisiae.
AB  - Yeast pyruvate decarboxylase (Pdc) catalyses the reaction at the branch-point of
      fermentation and respiration. In this work we have investigated the mechanisms of
      its transcriptional regulation in response to glucose and the non-fermentable
      carbon source ethanol. For this purpose we studied the function of different
      promoter fragments of PDC1, encoding the major pyruvate decarboxylase enzyme in
      wild-type cells, in the basal CYC1 promoter context. Thus, we identified a
      sequence mediating the response to ethanol and provide evidence showing that
      transcription of PDC1 is controlled by ethanol repression rather than by glucose
      induction. Furthermore, we showed that the same sequence is responsible for an
      autoregulatory process, leading to increased transcription from both the PDC1 and
      the PDC5 promoters, in strains in which the genomic copy of PDC1 is deleted. In
      addition, we have confirmed the role of Rap1 binding and have demonstrated that
      the Gcr1 protein also acts in transcriptional activation. DNA-protein
      interactions at the consensus Rap1-binding site and the newly identified ethanol
      repression sequence (5'-AAATGCATA-3', termed 'ERA') were investigated by gel
      shift and footprint analyses. Both DNA-binding activities were found in extracts
      from cells grown in media containing glucose or ethanol as the carbon source,
      indicating that the capacity to bind is not altered by the carbon source used.

PMID- 8866485
TI  - A secreted protein tyrosine phosphatase with modular effector domains in the
      bacterial pathogen Salmonella typhimurium.
AB  - A number of bacterial pathogens have evolved sophisticated strategies to subvert
      host-cell signal-transduction pathways for their own benefit. These bacteria
      produce and export proteins capable of specific interactions with key mammalian
      cell regulatory molecules in order to derail the normal functions of the cells.
      In this study, we describe the identification of a modular effector protein
      secreted by the bacterial pathogen Salmonella typhimurium that is required for
      its full display of virulence. Sequence analysis revealed that a carboxy-terminal
      region of this protein, which we have termed SptP, is homologous to the catalytic
      domains of protein tyrosine phosphatases. Purified SptP protein efficiently
      dephosphorylated peptide substrates phosphorylated on tyrosine. An engineered
      mutant of SptP in which a critical Cys residue in the catalytic domain was
      changed to Ser was devoid of phosphatase activity, indicating a catalytic
      mechanism similar to that of other tyrosine phosphatases. In addition, an amino
      terminal region of SptP exhibited sequence similarity to the ribosyltransferase
      exoenzyme S from Pseudomonas aeruginosa and the cytotoxin YopE from Yersinia spp.
      The modular nature of this effector protein may allow multiple interactions with
      host-cell signalling functions.

PMID- 8866486
TI  - Activation of transcription at divergent urea-dependent promoters by the urease
      gene regulator UreR.
AB  - The Proteus mirabilis and plasmid-encoded urease loci contain seven contiguous
      structural and accessory genes (ureDABCEFG) and the divergently transcribed ureR,
      which codes for an AraC-like transcriptional activator. Previously, it was shown
      that the plasmid-encoded ureR to ureD intergenic region contained divergent
      promoters (ureRp and ureDp). Transcription from these promoters required both the
      effector molecule urea and the activator protein UreR. In this report, we
      demonstrate that the P. mirabilis urease gene cluster contains similar divergent
      urea- and UreR-dependent promoters. The ureR gene products from either urease
      locus were able to activate transcription at both the plasmid-encoded and P.
      mirabilis promoters. The minimal concentration of urea required to activate
      transcription at ureRp or ureDp from either gene cluster was approximately 4 mM.
      The transcriptional start sites for the plasmid-encoded and P. mirabilis
      divergent promoters were similar in an Escherichia coli DH5 alpha background, as
      determined by primer-extension analysis. However, in P. mirabilis HI4320,
      transcription of ureR initiated predominately at an alternative site. Physical
      mapping and inhibition studies were used to localize the UreR-binding sites
      within the plasmid-encoded ureRp and ureDp intergenic sequences to regions of 68
      bp and 86 bp, respectively. Gel shift analysis demonstrated that UreR bound to a
      135 bp fragment in the approximate centre of the plasmid-encoded ureR to ureD
      intergenic region. The results presented here suggest that the P. mirabilis and
      plasmid-encoded urease gene clusters utilize similar mechanisms of
      transcriptional activation in response to urea.

PMID- 8866487
TI  - A consensus structure for sigma S-dependent promoters.

PMID- 8866488
TI  - Prospects for gene therapy in Parkinson's disease.
AB  - Numerous advances in in vivo and ex vivo gene-therapy approaches to Parkinson's
      disease offer promise for direct clinical trials in patients in the next several
      years. These systems are predicated on introducing gene that encode enzymes
      responsible for dopamine biosynthesis or neurotrophic factors that may delay
      nigrostriatal degeneration or facilitate regeneration. We review the current
      status of experimental approaches to gene therapy for Parkinson's disease.
      Comparative advantages and disadvantages of each system are enumerated, and
      preclinical trials of some of the systems are evaluated. Although the specific in
      vivo or ex vivo methods used for gene transfer into the brain are likely to be
      supplanted by newer technology over the next decade, the principles and
      approaches developed in current studies likely will remain the same.

PMID- 8866489
TI  - Improvement of severe postural cerebellar tremor in multiple sclerosis by chronic
      thalamic stimulation.
AB  - Tremor can be particularly disabling in patients with multiple sclerosis (MS) and
      is mildly improved by drug treatment. The efficiency of stereotactic thalamotomy
      has been reported in a small number of patients but was counterbalanced by severe
      postoperative complications. Stimulation of the thalamic ventral intermediate
      nucleus, which is a less aggressive surgical method, is efficient in essential
      and in parkinsonian tremors. We report here the results of thalamic stimulation
      in 13 patients with MS with tremor. All patients were subjected to clinical
      examination, videorecording, and quantification of the functional disability
      before surgery and 3 months postoperatively. The surgical intervention was well
      tolerated in all cases. A clear improvement of the tremor was observed in 69.2%
      of the patients. Functional improvement was more varied and depended on the
      severity of tremor and coexistence of other neurological symptoms. Of the eight
      most severely affected patients, seven recovered the possibility to easily catch
      an object and use it. The results indicate that thalamic stimulation may be
      useful in the treatment of severe postural cerebellar tremor in MS.

PMID- 8866490
TI  - Cabergoline in Parkinson's disease complicated by motor fluctuations.
AB  - Cabergoline is a long-acting D2 dopamine (DA) agonist. We conducted an open study
      to investigate the effectiveness and tolerability of cabergoline, administered
      once a day orally, in 50 consecutive patients with Parkinson's disease
      complicated by motor fluctuations and dyskinesias. In 15 patients cabergoline
      replaced another direct DA agonist. Evaluation after 6 months of treatment (also
      including patients who dropped out during this period), showed an improvement in
      off or on hours, or both, in excess of 50% in 27 patients, comprising 20 of the
      35 patients (57%) previously untreated with DA agonists and seven of the 15
      patients (47%) already on DA agonists when the study began. Of the 22 patients
      who received the treatment for 1 year, the improvement was maintained up to final
      evaluation in the patients not on DA agonists at admission (n = 16), whereas a
      slight deterioration in clinical condition was observed in the patients already
      on DA agonists at admission (n = 6). Only six patients showed a detectable
      increase in dyskinesias. The most common side effects were gastric upset (n =
      12), orthostatic hypotension (n = 3), and ankle edema (n = 3), all mild; also
      observed were two cases of pleural effusion/pulmonary fibrosis. Twenty patients
      (40%) failed to complete the treatment; of these, five (10% of total) dropped out
      because of adverse effects. It is concluded that once-daily administrations of
      cabergoline are useful for treating patients with Parkinson's disease with motor
      fluctuations and may advantageously substitute other DA agonists. The side
      effects of the drug are generally mild, although two cases involving
      pleuropulmonary complications did emerge.

PMID- 8866491
TI  - Quantitative gait analysis in patients with vascular parkinsonism.
AB  - Until now the clinical criteria for the diagnosis of vascular parkinsonism (VP)
      have been disputed. The purpose of the present study is to investigate whether
      quantitative gait analysis can differentiate between the gait pattern of patients
      with VP and the gait pattern of patients with idiopathic Parkinson's disease
      (PD). Twelve patients with VP, 12 patients with PD, and 10 neurologically
      nondiseased controls were examined by quantitative gait analysis. Patients with
      VP, having a similar gait velocity and stride length, showed relatively preserved
      arm swing with markedly more anteflexion in the shoulder on the forward sway of
      the arm swing than patients with PD. Patients with VP also showed less flexion
      dystonic posture of the elbow, hip, knee, and trunk than did patients with PD.
      There was no significant difference in the excursions and coordination of arm
      swing in the patients with VP compared with the control group. Both patient
      groups showed reduced leg movements, reduced hip extension, and reduced knee
      flexion and extension as compared with the controls.

PMID- 8866492
TI  - Influence of dopaminergic medication on automatic postural responses and balance
      impairment in Parkinson's disease.
AB  - It is still unclear why balance impairment in Parkinson's disease (PD) often
      responds insufficiently to dopaminergic medication. We have studied this issue in
      23 patients with idiopathic PD and 24 healthy controls. Our specific purposes
      were (a) to investigate the contribution of abnormal automatic postural responses
      to balance impairment in PD and (b) to assess the influence of dopaminergic
      medication on abnormal automatic postural responses and balance impairment.
      Standing subjects received 4 degrees "toe-up" rotational perturbations of a
      supporting forceplate. We bilaterally recorded posturally destabilizing medium
      latency (ML) responses from the stretched gastrocnemius muscles and functionally
      corrective long latency (LL) responses from the shortened tibialis anterior (TA)
      muscles. We also assessed changes in the center of foot pressure (CFP) and the
      center of gravity (COG). All patients were tested in the "off" and "on" phases.
      All controls were tested and retested after 1 h. During the off phase, we found
      enlarged ML amplitudes and diminished LL amplitudes in patients, together with a
      markedly increased posterior displacement of the COG. The abnormal ML and LL
      responses were partially responsible for the increased body sway in patients
      because the initial forward (destabilizing) displacement of the CFP was
      increased, while the subsequent backward displacement of the CFP (a measure of
      the corrective braking action of LL responses) was delayed. Abnormal late
      automatic or possibly more voluntary postural corrections also contributed
      substantially to the increased body sway. During the on phase, ML amplitudes were
      reduced in patients but remained increased compared with controls. LL amplitudes
      no longer differed between both groups due to a modest, possibly dopamine-related
      increase in patients and a simultaneous decrease in controls. The abnormal CFP
      displacement was only partially improved by dopaminergic medication. The later
      postural corrections were not improved at all. Consequently, the increased
      posterior COG displacement was not ameliorated during the on phase. We conclude
      that (a) a combination of abnormal automatic and perhaps more voluntary postural
      corrections contributes to increased body sway in PD and (b) dopaminergic
      medication fails to improve balance impairment in PD because early automatic
      postural responses are only partially corrected, while later occurring postural
      corrections are not improved at all. These electrophysiological results support
      clinical observations and suggest that nondopaminergic lesions play a significant
      role in the pathophysiology of postural abnormalities in PD.

PMID- 8866493
TI  - Reversal of behavioural abnormalities by fetal allografts in a novel rat model of
      striatonigral degeneration.
AB  - We have developed a rodent model of striatonigral degeneration, one of the core
      pathologies underlying the disease multiple system atrophy (MSA). 6
      Hydroxydopamine (6-OHDA) was administered into the left medial forebrain bundle
      of male Wistar rats, followed 3-4 weeks later by intrastriatal injection of
      quinolinic acid into the ipsilateral striatum. The 6-OHDA lesion resulted in
      ipsilateral rotation to (+)-amphetamine and contralateral rotation to
      apomorphine. Following the subsequent striatal lesion, amphetamine-induced
      ipsilateral rotation persisted, but apomorphine-induced contralateral rotation
      was reduced or abolished. Subsequently, the lesioned striatum was implanted with
      fetal CNS allografts consisting of cell suspensions derived from striatal
      primordium alone or combined with cografts of ventral mesencephalon. Cografted
      rats showed a reduction or reversal of amphetamine-induced rotation. This was not
      observed in animals receiving striatal grafts alone. Apomorphine-induced
      contralateral rotation was restored after striatal grafts alone, but only
      partially in animals receiving sham or cografts. Tyrosine hydroxylase (TH) and
      dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein
      (DARPP 32) immunocytochemistry showed mesencephalic and striatal graft survival
      in most animals. However, dopaminergic outgrowth was restricted to the graft
      deposit. The latter was surrounded by a markedly gliotic glial fibrillary acidic
      protein-positive capsule continuous with corpus callosum. Dopaminergic
      reinnervation of denervated and lesioned adult striatum itself was absent,
      suggesting that rotational recovery was due to diffuse dopamine release. The
      study shows that combined unilateral lesioning of rodent medial forebrain bundle
      and striatum results in a characteristic drug-induced rotational response that
      can be partly restored by mesencephalic/striatal cografts.

PMID- 8866494
TI  - Dentatorubral-pallidoluysian atrophy. Clinical features of a five-generation
      Danish family.
AB  - We describe the first Danish family with dentatorubral-pallidoluysian atrophy
      (DRPLA), containing 16 clinically affected individuals in five generations.
      Inheritance is autosomal dominant. The disorder was diagnosed as Huntington's
      disease (HD), but analysis of the IT15 gene for HD revealed normal alleles. The
      diagnosis of DRPLA was based on the finding of elongated CAG repeats in the B37
      gene on chromosome 12 in affected individuals. The age at onset ranged from 13 to
      60 years, with the most severe clinical picture being associated with onset in
      childhood. Clinical features included varying combinations of dementia, euphoria,
      visuomotor disturbances, speech problems, ataxia, tremor, epilepsy and
      involuntary movements presenting as chorea, athetosis, and dystonia. We discuss
      characteristics of DRPLA that may enable the differentiation from HD on a
      clinical basis. In conclusion, DRPLA should be considered and DNA analysis is
      recommended in patients manifesting varying combinations of extrapyramidal and
      cerebellar symptoms, especially when clinical features show pronounced
      intrafamilial variability, and dyscoordination, tremor, myoclonus, epilepsy, and
      euphoria are part of the syndrome.

PMID- 8866495
TI  - Characteristics of individuals with Huntington disease in long-term care.
AB  - This is a retrospective review of 97 Huntington disease (HD) patients living in
      long-term care facilities in the Twin Cities. The purpose of the study was to
      describe the demographic features, patterns of behavior, weight change, nursing
      issues, medication use, and hospitalization in this population. On admission to
      the nursing home, the "average" HD patient was of either sex, 45 years old,
      previously employed, a high school graduate, and not married. One third had
      severe behavior problems. Half gained and half lost weight; weight loss was not a
      predictor of death. Almost all used central nervous system-active drugs, most
      commonly neuroleptics. Eighty-four percent were ambulatory on admission, but 88%
      of those who died were nonambulatory at the time of death. We concluded that (a)
      HD patients are demographically different from other residents of long-term care
      facilities, (b) weight gain can occur in some late-stage patients, (c) negative
      behavior is a significant problem but is restricted to a subset of patients, and
      (d) adapting creatively to increasing multifaceted disability is the greatest
      challenge to the staff in facilities caring for HD patients.

PMID- 8866496
TI  - A controlled trial of idebenone in Huntington's disease.
AB  - One hundred patients with clinically diagnosed Huntington's disease (HD) were
      randomized to either idebenone, an antioxidant and enhancer of oxidative
      metabolism, or placebo, in a 1-year, double-blind, parallel-group study aimed at
      slowing the rate of progression of the disease. Ninety-one patients completed the
      study. There were no significant differences between groups on the primary
      outcome measures of the Huntington's Disease Activities of Daily Living Scale
      (ADL-an index of functional status) and the Quantified Neurologic Examination
      (QNE). Sample size calculations based on progression of the ADL and QNE in this
      study group revealed that a larger study group is necessary to detect any
      differences less than an almost complete halting of the disease. This argues for
      multicenter efforts for future therapeutic trials in HD.

PMID- 8866497
TI  - Hashimoto's myoclonic encephalopathy: an underdiagnosed treatable condition?
AB  - We report two patients with subacute diffuse encephalopathy characterized by
      confusion, myoclonic encephalopathy, and mild akineto-rigid extrapyramidal signs
      in one case and by apathy, memory deficit, and partial complex seizures in the
      other. Hashimoto's thyroiditis with high titers of anti-thyroglobulin antibodies
      was diagnosed in both patients, who were unresponsive to anticonvulsant
      medication, but showed rapid neurological improvement following steroid
      treatment. On neuropsychological examination, predominant frontotemporal
      dysfunction was noted. Electroencephalographic activity was remarkable for its
      rhythmical delta activity, unresponsive to, or even paradoxically increased by,
      anticonvulsant treatment. On magnetic resonance imaging, atrophy with temporal
      predominance was found. These observations support the idea that this potentially
      treatable dementia and movement disorder should be classified as a separate
      clinical entity.

PMID- 8866498
TI  - Severe motor tics causing cervical myelopathy in Tourette's syndrome.
AB  - We describe two patients with Tourette's syndrome in whom severe motor tics
      involving the neck were complicated by cervical myelopathy. The first patient, a
      21-year-old man, had complex tics consisting of violent twisting and extending
      movements of the neck preceded by an irresistible urge to produce the abnormal
      postures. Two years after onset of these tics, paraesthesias, sensory deficits up
      to the level of C4, and a gait disturbance developed. Neuroimaging studies
      confirmed compressive myelopathy, and the symptoms gradually improved with
      botulinum toxin injections in the posterior cervical muscles. The second patient,
      a 42-year-old man, had violent clonic tics consisting of thrusting head jerks.
      The repetitive flexion-extension neck movements had been present since the age 10
      years. At age 23, he developed progressive weakness of all four extremities and
      bladder and sexual dysfunction. Myelography demonstrated cervical spinal canal
      stenosis with retrospondylosis from C3 through C5 and a Klippel-Feil
      malformation. After cervical decompression by C3-C5 laminectomies, his spinal
      cord symptoms improved temporarily. The tics, however, continued, and the
      neurologic deficits of cervical myelopathy progressed again after age 34. He did
      not benefit from a second operation. This report draws attention to the
      possibility that some tics can produce disabling compressive myelopathy. Early
      diagnosis and treatment of the movement disorder is essential in such cases.

PMID- 8866499
TI  - Postencephalitic stereotyped involuntary movements responsive to L-Dopa.
AB  - In 1954, at the age of 5 years, our patient had an encephalitic syndrome
      associated with a prolonged lethargic state. After this episode, he developed a
      severe parkinsonian syndrome that, after a few years, was associated with axial
      dystonia and stereotyped abnormal movements of the upper limbs. This complex and
      progressive extrapyramidal syndrome had many similarities to the encephalitis
      lethargica as described by von Economo. Results of cerebral computed tomography
      and magnetic resonance imaging were normal. Fluorodopa positron emission
      tomography showed a significant bilateral reduction of tracer accumulation in
      both putamen, similar to that observed in patients with idiopathic Parkinson's
      disease. However, in this patient, treatment with L-Dopa suppressed all akinetic,
      dystonic and dyskinetic symptoms. The effectiveness of L-Dopa was abolished by
      administration of a D2 antagonist and was fully reproduced by a D2 agonist. In
      conclusion, this patient presented a complex postencephalitic, extrapyramidal
      syndrome, with akinetic symptoms and involuntary movements. These symptoms
      appeared to be related to a limited lesion of the dopaminergic neurons of the
      zona compacta of the substantia nigra.

PMID- 8866500
TI  - Bilateral myoclonus of the trapezius muscles after distal lesion of an accessory
      nerve.
AB  - Observations of rhythmic or semirhythmic myoclonus due to a peripheral nerve
      lesion are exceptional. We report on a patient with thorax trauma with multiple
      bilateral hematomas of the paravertebral musculature. Eight years later he
      developed rhythmic myoclonus of both trapezius muscles and thoracic pain.
      Infiltration of a paramedially located scar at the level of D5-6 with a local
      anesthetic agent led to an intermittent relief of the myoclonus as did anesthetic
      blockade of the left accessory nerve. Surgical excision of the scar, which
      contained multiple dystrophic axons on histological examination, cured the
      patient's symptoms as illustrated in a videotape. This indicates that peripheral
      afferents contributed to the myoclonus. Ephaptic transmission, ectopic
      excitation, or misdirected neuronal sprouting secondary to the trauma are
      possible peripheral mechanisms responsible for the movement disorder. Successful
      blockade of the left accessory nerve with bilateral relief of the symptoms
      suggests a secondary, more centrally located mechanism, e.g., in the brain stem,
      probably driven by an altered afferent input. It is concluded that rhythmic or
      semirhythmic and focal myoclonus need a careful workup to look for a peripheral
      cause because such a condition would be accessible for surgical treatment.

PMID- 8866501
TI  - Persisting "writer's cramp" as a result of compensation of a temporary palsy due
      to a hereditary neuropathy with liability to pressure palsies.
AB  - A 49-year-old man reported several periods of acute paresis of different nerves
      after exposure to pressure. All palsies showed a good recovery over a period of
      days to months. The suspected diagnosis of a hereditary neuropathy with liability
      to pressure palsies was confirmed by the histology of a suralis nerve biopsy,
      which showed a distinct tomaculous swelling of the myelin. Nine years ago he
      noticed an acute, distally pronounced palsy of the right arm. A brachial plexus
      lesion was diagnosed. His profession required written work, thereby forcing him
      to compensate this weakness by increasing the coactivation of the elbow and upper
      arm. This coactivation persisted even after complete recovery from the plexus
      palsy. Thus, the patient showed the typical feature of classical writer's cramp,
      with broad coactivation of the arm muscles, which has continued to the present.
      At the same time, however, the patient was able to perform other motoric tasks
      well, such as painting. After several practice sessions with a special program
      that makes use of preserved motor abilities to reestablish writing, the patient
      was again able to write with a normal kinematic profile as documented by the
      recorded handwriting. This suggests that the "writer's cramp" of our patient is
      one form of task-related dystonia that may be related more to the perserveration
      of a misleading motor strategy than to a general inability of the motor system to
      control the movement properly.

PMID- 8866502
TI  - Acute pharmacologic blockade of dyskinesias in Parkinson's disease.

PMID- 8866503
TI  - Fluoxetine in Parkinson's disease.

PMID- 8866504
TI  - An estimate of the risk of movement disorders associated with the chronic use of
      clebopride.

PMID- 8866505
TI  - Lesch-Nyhan variant: dystonia, ataxia, near-normal intelligence, and no self
      mutilation.

PMID- 8866506
TI  - Transient atrial fibrillation after subcutaneous apomorphine bolus.

PMID- 8866507
TI  - Tardive lingual dystonia treated with clozapine.

PMID- 8866508
TI  - Raynaud's phenomenon in a case of multiple system atrophy.

PMID- 8866509
TI  - Manganese and chronic liver disease.

PMID- 8866510
TI  - A review and critique of the process approach in neuropsychological assessment.
AB  - This paper surveys the process approach literature with an emphasis on higher
      level cognitive functions like attention and concentration, learning and memory,
      and problem solving and executive functioning. In particular, it discusses
      organizational strategies and kinds of errors found on a variety of tests as well
      as behavioral, situational, and interpersonal issues as they relate to test
      procedures. It critiques the process approach and suggests future directions.

PMID- 8866512
TI  - Calcium-binding proteins in primate basal ganglia.
AB  - This paper describes the distribution of the calcium-binding proteins calbindin
      D28k. Parvalbumin and calretinin in primate basal ganglia. The data derive from
      immunocytochemical studies undertaken in squirrel monkeys (Saimiri sciureus) and
      in normal human individuals. In the striatum, calbindin labels medium-sized spiny
      projection neurons whereas parvalbumin and calretinin mark two separate classes
      of aspiny interneurons. The striatal matrix compartment is markedly enriched with
      calbindin while striatal patches (striosomes) display a calretinin-rich neuropil.
      In the pallidum, virtually all neurons contain parvalbumin but none express
      calbindin. Calretinin occurs only in a small subpopulation of both large and
      small pallidal neurons. In the subthalamic nucleus, there exists a multitude of
      parvalbumun-positive cells and fibers but the number of calretinin and calbindin
      positive neuronal elements is small. In the substantia nigra/ventral tegmental
      area complex, calbindin and calretinin occur principally in dopaminergic neurons
      of the dorsal tier of the pars compacta and in those of the ventral tegmental
      area. Parvalbumin is strictly confined to the GABAergic neurons of the pars
      reticulata and lateralis. Calbindin-rich fibers abound in the pars reticulata and
      lateralis, while calretinin-positive axons are confined to the pars compacta.
      These results indicate that calbindin and parvalbumin are distributed according
      to a strikingly complementary pattern in primate basal ganglia. Calretinin is
      less ubiquitous but occurs in all basal ganglia components where it labels
      distinct subsets of neurons. Such highly specific patterns of distribution
      indicate that calbindin, parvalbumin and calretinin may work in synergy within
      primate basal ganglia.

PMID- 8866511
TI  - Developmental dyspraxia and developmental coordination disorder.
AB  - This article discusses the role developmental dyspraxia plays in developmental
      coordination disorder (DCD), based upon a review of literature on apraxia,
      developmental dyspraxia, and DCD. Apraxia and dyspraxia have often been equated
      with DCD. However, it is argued that apraxia and dyspraxia primarily refer to the
      problems of motor sequencing and selection, which not all children with DCD
      exhibit. The author proposes to distinguish developmental dyspraxia from DCD.
      Other issues discussed include the assessment, etiology, and treatment of
      developmental dyspraxia and DCD, and the relationship between DCD and learning
      disabilities. A research agenda is offered regarding future directions to
      overcome current limitation.

PMID- 8866513
TI  - Opposite effects of increased intracellular cyclic AMP on the heat and bradykinin
      responses of canine visceral polymodal receptors in vitro.
AB  - To clarify the validity of the long standing hypothesis that effects of E series
      prostaglandin (PG)S are mediated by cyclic AMP (cAMP), we studied the effects of
      increases in intracellular cAMP on the heat and bradykinin responses of
      testicular polymodal receptors. Polymodal receptor activities were recorded in
      vitro from testis-spermatic nerve preparations excised from dogs anesthetized
      with pentobarbital (30 mg/kg, i.v.). Increases in intracellular cAMP induced by
      either forskolin (5 or 10 microM), an adenylyl cyclase activator, or a mixture of
      dibutyryl cAMP (20-100 microM), a membrane permeable cAMP analog, and 3-isobutyl
      1-methyl xanthine (20-100 microM), an inhibitor of the cAMP degrading enzyme,
      significantly augmented the response to heat (42-48 degrees C). In contrast,
      these substances failed to facilitate the response to bradykinin (0.1 or 1
      microM) and instead suppressed it. Dideoxyforskolin (10 microM), an inactive
      analog of forskolin, had no effects on both the heat and bradykinin responses.
      These results demonstrate that an increase in intracellular cAMP induces opposite
      effects on the heat and bradykinin responses. Possible involvement of
      intracellular cAMP in the facilitatory effects of PGE2 on both responses was
      discussed in connection with the PGE receptor subtypes involved in the
      sensitization of the bradykinin and heat responses.

PMID- 8866514
TI  - Intracellular free Na+ concentration increases in cultured retinal cells under
      oxidative stress conditions.
AB  - The effect of oxidative stress, induced by ascorbate/Fe2+, on the intracellular
      free Na+ concentration ([Na+]i) of cultured chick retina cells was determined
      using the fluorescent indicator Na(+)-binding benzofuran isophthalate (SBFI). The
      resting[Na+]i of retina cells submitted to oxidative stress (15.5 +/- 1.9 mM) was
      significantly higher than that of control cells (8.9 +/- 0.8 mM). KCl (50 mM)
      depolarization induced a sustained [Na+]i increase (delta[Na+]i), which was
      significantly higher in peroxidized cells (8.1 +/- 0.7 mM) than in control cells
      (4.9 +/- 0.9 mM). The glutamate receptor antagonists, MK-801 and CNQX, reduced
      more significantly the initial delta[Na+]i induced by K(+)-depolarization under
      oxidative stress conditions (65% of inhibition), than in control cells (20% of
      inhibition). Moreover, in the presence of MK-801 and CNQX the increase in the
      [Na+]i, which was similar in control and peroxidized cells, was followed by a
      decrease towards a plateau. The Na+ channel blocker, tetrodotoxin (TTX), also
      reduced the sustained increase of the [Na+]i evoked by 50 mM KCl in both
      experimental conditions. However, TTX and glutamate receptor antagonists tested
      together failed to abolish the delta[Na+]i upon K(+)-depolarization, indicating
      that TTX-resistant Na+ channels were involved in the Na+ influx. The entry of Na+
      through these channels contributed mainly to the early phase of the [Na+]i rise
      upon K(+)-depolarization, whereas the glutamate receptors seem to contribute more
      significantly to the [Na+]i response for stimulations longer than 30-50 s. The
      results suggest that an excessive activation of glutamate receptors increases the
      influx of Na+ and the resting [Na+]i under oxidative stress conditions.

PMID- 8866515
TI  - Zinc protoporphyrin IX suppresses nitric oxide production through a loss of L
      arginine in rat cerebellar slices.
AB  - Zinc protoporphyrin IX (ZnPP) inhibits production of carbon monoxide (CO) but not
      nitric oxide (NO) synthase activity in vitro, therefore, it has been used to
      discriminate the effects of these activators of cyclic GMP production. However,
      intracellular enzyme activity is supported by endogenous substrates and
      cofactors, therefore, in vitro experiments with an optimal supply of these
      substances do not necessarily represent the intracellular circumstances. The
      present study was conducted to examine whether ZnPP affects NO production in rat
      cerebellar slices. Incubation with 1-aminocyclopentane-trans-1,3-dicarboxylic
      acid (ACPD) increased the conversion of [3H]-L-arginine into [3H]-citrulline in
      the slices. ZnPP at I microM, not only suppressed the ACPD-dependent production
      of [3H]-citrulline but also reduced the basal [3H]-citrulline level, accumulation
      of [3H]-L-arginine and ATP content in the slices, but ZnPP at 1 microM did not
      affect the catalytic activity of partially purified NO synthases in vitro. In
      contrast, a selective inhibitor of NO synthase, N omega(-)nitro-L-arginine,
      inhibited ACPD-dependent [3H]-citrulline production without affecting the basal
      [3H]-citrulline level or [3H]-L-arginine accumulation. These results indicate
      that ZnPP suppresses No production through a loss of its precursor, even at
      concentrations exhibiting no inhibition of the catalytic activity of NO synthase.
      It is concluded that ACPD activates NO synthase in the slice and that ZnPP cannot
      discriminate the roles of CO from NO in cyclic GMP production in brain slices.

PMID- 8866516
TI  - Peripheral axotomy induces increased expression of neurotensin in large neurons
      in rat lumbar dorsal root ganglia.
AB  - In normal rat lumbar 4 and 5 dorsal root ganglia (DRGs) a few large neurons
      expressed neurotensin-like immunoreactivity (LI). Twenty hours after crushing the
      lumbar 4 and 5 dorsal roots or the sciatic nerve, accumulations of neurotensin-LI
      were seen in many nerve fibers on the ganglionic side of both crushes, indicating
      a significant centrifugal transport of neurotensin under normal circumstances. A
      distinct increase in expression of neurotensin (peptide and mRNA) was observed in
      many large neuron profiles in the ipsilateral lumbar 4 and 5 DRGs two days after
      unilateral sciatic nerve transection. Two weeks after axotomy the number of
      neurotensin-positive neuron profiles was reduced and had almost reached normal
      levels. In the superficial dorsal horn of the lesion side the number of
      neurotensin immunoreactive fibers in laminae I-II was markedly reduced 7 days
      after peripheral axotomy. There was no detectable increase in neurotensin-L1 in
      laminae III-IV of spinal dorsal horn, in the dorsal column nuclei or in the
      peripheral neuroma (2-28 days after axotomy), suggesting that the amounts of
      neurotensin transported centrifugally from DRG neurons after axotomy are low.
      Neurotensin-LI only sometimes colocalized with neuropeptide Y-LI, another peptide
      known to be upregulated in large DRG neurons. These two peptides may therefore
      partly be localized in different populations of large DRG neurons. The present
      results show that, in contrast to the nerve injury-induced general downregulation
      of neurotensin systems in the superficial dorsal horn and of neurotensin receptor
      mRNA expression in DRGs as shown in previous studies, axotomy causes upregulation
      of expression of neurotensin peptide in some large DRG neurons.

PMID- 8866517
TI  - Increased nasal mucosal blood flow, airway resistance and secretion induced by
      electrical stimulation of the superior salivatory nucleus in cats.
AB  - We studied the effects of electrical stimulation of the superior salivatory
      nucleus (SSN) on the nasal blood flow, nasal airway resistance, and nasal
      secretion in ketamine or pentobarbital anesthetized cats. The blood flow of the
      nasal mucosa was measured by laser Doppler flowmetry. Similar to the effects of
      stimulation of the parasympathetic nerve innervating the nasal mucosa, the SSN
      stimulation increased the nasal blood flow, nasal airway resistance, and nasal
      secretion on the ipsilateral side. These responses were not accompanied by
      changes in contralateral nasal blood flow, ipsilateral forelimb blood flow, blood
      pressure, or orofacial movement. Atropine administration partially inhibited the
      SSN-induced nasal vasodilation without interfering with the effect on the nasal
      airway resistance. This vasodilatation was not affected by sympathectomy or
      guanethidine administration, but it was abolished by hexamethonium
      administration. It is suspected that the cells in the SSN control both nasal
      vasodilatation and secretion, and that the SSN output fibers responsible for the
      nasal parasympathetic control consist of both cholinergic and non-cholinergic
      fibers.

PMID- 8866518
TI  - Correlation of in vivo nitric oxide and cGMP with glutamate/glutamine metabolism
      in the rat striatum.
AB  - We have examined how the suppression of endogenous production of nitric oxide
      (NO) in the striatal tissue affects release of glutamate (GLU) and glutamine
      (GLN) in pentobarbital-anesthetized male Sprague-Dawley rats. For the
      quantitative measurement of tissue NO production and amino acid release, an in
      vivo assay system for extracellular nitrite (NO2-) and amino acids was employed
      using an in vivo microdialysis technique. An NO synthase inhibitor (NG-nitro-L
      arginine methyl ester, L-NAME) in concentrations ranging between 4-40 mM was
      perfused into the rat striatum using the assay system. Tissue NO production was
      found to be inversely proportional to the L-NAME concentration. L-NAME likewise
      decreased striatal levels of GLU and GLN. Furthermore, tissue NO production
      showed a positive correlation with GLU (R = 0.62, P < 0.02) and GLN (R = 0.86, P
      < 0.001) concentrations. Exogenous application of NO and cGMP by intrastriatal
      perfusion with 0.1-2.5 mM hydroxylamine and 0.4-10 mM 8-bromo-cGMP, respectively,
      increased striatal GLU release in a dose-related manner. Hydroxylamine reduced
      GLN release, and 8-bromo-cGMP showed a tendency to decrease GLN. In conclusion,
      striatal GLU/GLN metabolism is a function of the tissue concentration of NO.
      Normal endogenous concentration of NO causes GLU to be released at a consistent
      basal level, and enhanced tissue NO production facilitates GLU release via
      pathways including cGMP formation. We hypothesize that NO may suppress GLN
      formation by astrocytes.

PMID- 8866519
TI  - Recurrent inhibition in amygdalo-cortical projection neurons of the rat via
      collaterals of fast-conducting axons.
AB  - On stimulation of the medial prefrontal cortex (mPFC) of the rat, the amygdala
      neurons projecting to the mPFC exhibited an IPSP, which caused IS-SD blockage in
      the antidromic spikes of these neurons. The IPSP was not preceded by EPSP, but
      was not monosynaptic in nature. Its onset latencies were mostly confined to
      within 10 ms, which was shorter than the time for orthodromic conduction from the
      mPFC to the amygdala. The findings indicated that the IPSP was produced via
      recurrent collaterals of the amygdalo-cortical projection neurons. In view of the
      wide range of distribution of the time for antidromic conduction in the amygdalo
      cortical projection neurons (3.4-27.2 ms), the projection neurons with a fast
      conducting axon were considered to be responsible for the mPFC-evoked recurrent
      IPSP.

PMID- 8866520
TI  - Adaptive changes in human smooth pursuit eye movement.
AB  - Adaptive changes in initial eye velocity of pursuit eye movement were examined in
      nine normal subjects using a target that moved in a multiple ramp fashion.
      Significant changes in initial eye velocity occurred rapidly after training in
      six of the subjects. The magnitude and direction of the induced changes were a
      function of the training conditions. Adaptive changes started 100-200 ms after
      onset of pursuit eye movement (usually 140 ms), suggesting that the late (but not
      early) component of initial eye velocity was under adaptive control by our
      training paradigms.

PMID- 8866521
TI  - Depolarization with high-K+ causes Ca(2+)-independent but partially Cl(-)
      dependent glutamate release in rat hippocampal slice cultures.
AB  - We studied the neurotoxic glutamate release induced by high-K+ depolarization in
      rat hippocampal slice cultures. Depolarization with 90 mM K+ for 30 min caused a
      significant, three-fold increase in glutamate release. This release was not
      inhibited by removing extracellular Ca2+, but was significantly inhibited by
      replacement of extracellular Cl- with SO4(2-). These findings suggest that
      glutamate is released by mechanisms other than conventional vesicular release
      under the high-K+ condition.

PMID- 8866522
TI  - Estrogen and apoptosis in the developing sexually dimorphic preoptic area in
      female rats.
AB  - Effect of estrogen on apoptotic cell death was studied in the two sexually
      dimorphic neuronal groups in the developing rat preoptic area (POA): the
      anteroventral periventricular nucleus of the POA (AVPvN-POA); and the sexually
      dimorphic nucleus of the POA (SDN-POA). A specific labelling of nuclear
      fragmentation was performed by terminal deoxynucleotydyl transferase(TdT)
      mediated dUTP-biotin nick end-labeling method (TUNEL method) to demonstrate
      apoptosis. In the AVPvN-POA whose size is larger in females than in males, the
      number of TUNEL-positive cells was not significantly different between day 5
      control and female pups sacrificed 10 h after 25 micrograms estradiol benzoate
      (EB) injection. However, TUNEL-positive cells showed a significant increase in
      the female pups sacrificed 24 h after EB injection, compared to that shown in the
      control female pups. In the SDN-POA whose size is larger in males than in
      females, EB injection significantly decreased TUNEL-positive cells in the female
      pups sacrificed 24 h after EB injection, compared to that in controls. These
      results suggest that estrogen regulates the neuronal number by facilitating
      apoptotic cell death in the developing AVPvN-POA or by inhibiting it in the
      developing SDN-POA.

PMID- 8866523
TI  - Symposium on computerized behavioral testing of humans in neurotoxicology
      research: overview of the proceedings.
AB  - The Symposium on Computerized Behavioral Testing of Humans in Neurotoxicology
      Research, held in Portland, OR (USA), on June 21-23, 1995, is the subject of the
      23 articles in this issue of Neurotoxicology and Teratology. It is the first open
      forum to focus exclusively on computer-implemented behavioral test methods for
      neurotoxicology. Both the Symposium and this proceedings have been organized
      around the topics: new technologies and new batteries, confounders and
      methodologic factors, special populations (children), sensory and motor testing,
      clinical applications, and neurotoxicology research. The Symposium emphasized
      common approaches to computerized testing, highlighted fundamental differences in
      strategies for the selection of tests, and produced tangible evidence that the
      NES2 test battery has become a pervasively used instrument for presenting valid
      tests in human neurotoxicology research. However, the dominant impression drawn
      from the Symposium is that there is a methodologic vigor in the field of
      computerized behavioral testing. This is revealed by the appearance of new test
      batteries, criticism of existing procedures, challenges to the existing order of
      test selection, and the identification of analytic covariates for commonly used
      tests.

PMID- 8866524
TI  - Historical overview of computerized behavioral testing of humans in
      neurotoxicology.
AB  - Since the early 1970s, when they became more accessible, computers have been used
      increasingly for behavior measurement over a wide range of purposes, including
      the detection of neurotoxic effects. Over these relatively few years, the number
      of computerized tests in use in neurotoxicology has grown from one or two to
      around 16 major batteries. The development of computerized tests in
      neurotoxicology has been influenced by a number of drives or influences. Some of
      these influences have included the push for computerizing traditional paper-and
      pencil tests, the moves to develop a standard or core test battery, the emphasis
      on culture-free tests, and on the pragmatic screening approach to test selection.
      Lately, there has been more emphasis on the development of tests with stability
      and reliability. These influences have made, and are still making, some impact on
      the directions of test and test battery construction. The nature and degree of
      impact will be discussed in the context of analyzing the development of
      computerized behavioral testing to its current state.

PMID- 8866525
TI  - Cognitive neurotoxicology: a luxury or necessity?
AB  - Impaired psychological test performance is often observed at concentrations of a
      neurotoxicant below those producing harmful effects on other organ systems. The
      importance of this distinctive susceptibility lies in the opportunity it provides
      for the early detection of dysfunction. From this perspective, it is essential to
      evolve sensitive psychological methods for studying these states of marginal
      toxicity. It is argued that a cognitive approach provides the necessary degree of
      sensitivity and specificity for characterizing these states. Given the growing
      interest in using cognitive models to assess minor dysfunction in areas outside
      neurotoxicology, it is further argued that theoretically motivated methods can no
      longer be considered a luxury for neurotoxicological work. It is concluded that
      there are at least two advantages to this approach. First, it provides a
      theoretical framework for organising data. Second, establishing and developing
      links to substantive areas of cognitive investigation outside neurotoxicology
      will allow cross-fertilization to occur on a scientific level and provide a more
      convincing basis for action on a regulatory level.

PMID- 8866526
TI  - Development of a computer-based battery designed to screen adults for
      neuropsychological impairment.
AB  - The initial step in the development of a new computer-based neuropsychological
      testing system is described. A new hardware-software system and a screening
      battery consisting of an orientation task and five cognitive tests has been
      implemented. This novel screening battery is designed for use in identifying
      individuals among exposed groups who may require more extensive follow-up
      neuropsychological evaluation. Sophisticated, but currently available, and
      relatively inexpensive hardware and software technology are employed, introducing
      an improvement over existing computer-based batteries. Use of a digitized speech
      production device for producing instructions facilitates testing of illiterate
      subjects, use of auditory stimulus materials, and relatively easy translation of
      the testing instructions to other languages. Use of a pen-based notebook computer
      enables responding by the subject in a manner that is both natural and analogous
      to that used in existing paper-and-pencil testing instruments. Five
      neuropsychological tests were developed to cover a range of cognitive domains: 1)
      verbal list learning and recognition memory, 2) visual memory span, 3) conceptual
      and motor tracking, 4) psychomotor speed and accuracy, and 5) delayed verbal
      recognition. The screening instrument has been pilot-tested for feasibility of
      use among outpatients at an occupational medicine clinic and among community
      dwelling older adults. This instrument is intended to provide a standardized
      efficient, cost-effective method for widespread use in occupational medicine and
      public health to detect and track subclinical neurotoxic effects and to prevent
      additional harmful exposure. Additional aspects of development of the computer
      based testing system are discussed.

PMID- 8866527
TI  - Human behavioral assessment in neurotoxicology: producing appropriate test
      performance with written and shaping instructions.
AB  - Neurotoxic effects are of such breadth and complexity that functional biomarkers
      (behavioral tests) that integrate many areas of the nervous system predominate in
      human neurotoxicology research. The increasing distribution of chemical and other
      manufacturing throughout the world, particularly in developing nations, suggests
      the acute need to develop biomarkers for chemical exposures and effects that can
      be employed internationally. A language-free method for training performance on
      behavioral tests is described, which holds promise for international research
      that circumvents the vagaries of translation. Four behavioral tests were
      administered to 74-114 adult US subjects. Procedures, collectively termed
      shaping, produced effective performance on three tests [Symbol Digit, Vigilant
      Attention Test (VAT), Digit Span Forward and Backward], and produced appropriate
      but unacceptably slow performance in initial testing on the Simple Reaction Time
      test. Effective performance on the Symbol-Digit test also was produced by shaping
      instruction, without assistance from examiners, in small groups of residents of
      Taipei (Taiwan) and US children between the ages of 5 and 16.

PMID- 8866528
TI  - NES test performance in a large US Army veteran sample: relationships with both
      demographic factors and traditional neuropsychological measures.
AB  - A large sample of Vietnam-era US Army veterans completed a set of 16
      neuropsychological tests, including six computer-based tests from the
      Neurobehavioral Evaluation System (NES), during medical examinations supervised
      by the US Centers for Disease Control (CDC). Data for 881 participants of the
      Agent Orange Validation Study (AOV) and Vietnam Experience Study (VES) were
      available for analysis from public access data tapes provided by CDC. Information
      was available for several potential covariates from demographic questionnaires, a
      medical examination, and a medical history. Explorator, principal components
      factor analysis of 16 test variables yielded four factors, including one on which
      most of the NES tests loaded. The single best predictor of most
      neuropsychological performance variables was an index of general intellectual
      level as measured at entry into the Army almost 20 years before the
      neuropsychological examinations. Alcohol drinking variables were not related to
      neuropsychological performance. Several measures of general intelligence were
      compared for use as covariates of neuropsychological test performance. All were
      superior to years of education in statistically controlling for general
      intellectual level.

PMID- 8866529
TI  - The influence of vision on computerized neurobehavioral test scores: a proposal
      for improving test protocols.
AB  - Computerized tests of neurobehavioral function are frequently administered in
      neurotoxicological studies with little attention given to the optical properties
      of test stimuli or to the vision of subjects. Yet many test stimuli are small or
      briefly presented, and test endpoints often involve short reaction times.
      Stimulus detection and reaction time are known to be strongly dependent upon
      stimulus luminance, contrast, and size, as well as on the subject's visual
      abilities. The current study assessed the influence of visual contrast
      sensitivity on Neurobehavioral Evaluation System 2 (NES2) test results in three
      data sets. Analyses indicated that vision was associated with up to 24% of the
      variance (Hand Eye Coordination test) in NES2 scores, even when visual acuity was
      normal, and that vision often influenced the significance of group differences.
      It is suggested that researchers measure the luminance, contrast, and size of
      test stimuli, the distance from the subject's eyes to the monitor, and the
      subject's visual contrast sensitivity. The measurement and control of stimulus
      parameters and the inclusion of visual function scores in analysis models could
      reduce the variability among computerized test scores both within and between
      studies. Models that assess the influence of vision on computerized test results
      may help to identify the CNS domains and specialized functions adversely affected
      by neurotoxicant exposures.

PMID- 8866530
TI  - Analyzing multivariate neurobehavioral outcomes in occupational studies: a
      comparison of approaches.
AB  - Neurobehavioral studies often employ test batteries and confront issues of
      multiple testing and comparability between batteries. We have organized our
      battery of 12 tests into areas of neurobehavioral function to reduce the number
      of reported results, provide greater statistical power, and improve
      interpretability of the results. We explored several different organizational and
      statistical methods of creating summary scores including a priori groupings based
      upon clinical experience and factor analysis. We compared the sensitivity of
      these summary scores to performance changes associated with exposure to styrene
      in the manufacture of reinforced plastics. Our results demonstrated dramatic
      increases in power to detect exposure related changes compared to using
      individual test scores. Furthermore, the various methods provided generally
      compatible and comparable results. We encourage other neurobehavioral
      investigators to pursue and refine this approach.

PMID- 8866531
TI  - Computerized neurobehavioral testing: techniques for improving test instructions.
AB  - The development of new computer-administered neuropsychological tests has brought
      a renewed focus on the issue of written instructions. Designers and programmers
      often fail to take advantage of the display options and feedback potential
      available in modern computer systems to maximize the effectiveness of the
      instruction process. Guidelines from computer interface architecture and
      behavioral analysis are combined to present three principles for written
      instructions: precise language, attention focusing, and interactive instruction.
      A comparison of different instruction formats in the Symbol-Digit and Simple
      Reaction Time tests shows that the application of these principles can reduce
      training time without degrading performance.

PMID- 8866532
TI  - Feasibility and validity of three computer-assisted neurobehavioral tests in 7
      year-old children.
AB  - Three tests from the computerized Neurobehavioral Examination System (NES) were
      administered to a group of 917 Faroese children at approximately 7 years of age.
      The NES Continuous Performance Test (CPT) was modified to use animal silhouettes
      as stimuli instead of letters. Almost all children completed Finger Tapping (FT),
      the modified CPT, and Hand-Eye Coordination (HE). However, 18% of the children
      missed at least 25% of the stimuli on the CPT (full test period), and 37% of the
      children did not improve their HE performance by at least 10%, as compared to the
      first trial. Boys obtained better results than girls, and older children
      performed better than younger ones. However, both factors were confounded by
      acquaintance with computer games. Children who used glasses, who had strabismus,
      or who had decreased contrast sensitivity obtained less satisfactory scores,
      especially on CPT and HE. The NES performance was significantly associated with
      functional neurological performance, including catching a ball, diadochokinesia,
      and finger agnosia. Slight, though statistically significant, decrements were
      seen with increased levels of prenatal exposure to neurotoxicants, as indicated
      by the mercury concentrations in cord blood obtained at the time of birth. In
      conclusion, the tests were feasible in this age group after slight modifications,
      and the test results showed meaningful associations with major predictors, thus
      supporting the validity of the data.

PMID- 8866533
TI  - Neurobehavioral Evaluation System (NES): comparative performance of 2nd-, 4th-,
      and 8th-grade Czech children.
AB  - The Neurobehavioral Evaluation System was designed for field studies of workers,
      but many NES tests can be performed satisfactorily by children as young as 7 or 8
      years old and a few tests, such as simple reaction time, can be performed by
      preschool children. However, little comparative data from children of different
      ages or grade levels are available. Studies of school children in the Czech
      Republic indicate that 2nd-grade children could perform the following NES tests
      satisfactorily: Finger Tapping, Visual Digit Span. Continuous Performance, Symbol
      Digit Substitution, Pattern Comparison, and simpler conditions of Switching
      Attention. Comparative scores of boys and girls from the 2nd, 4th, and 8th grades
      and power analyses to estimate appropriate sample size were presented.
      Performance varied systematically with grade level and gender. Larger samples
      were needed with younger children to achieve comparable levels of statistical
      power. Gender comparisons indicated that boys responded faster, but made more
      errors than girls.

PMID- 8866534
TI  - Selective approaches to basic neurobehavioral testing of children in
      environmental health studies.
AB  - To identify neurotoxic effects in children living near hazardous waste sites, the
      Agency for Toxic Substances and Disease Registry (ATSDR) has designed a basic
      Pediatric Environmental Neurobehavioral Test Battery (PENTB) for children 1
      through 16 years of age. It emphasizes tests appropriate to the stages of a
      child's development. These stages were fundamental factors in selecting tests for
      the PENTB, which includes both informant- and performance-based assessment
      procedures. Assessment of children under 4 years of age is restricted to four
      informant-based instruments, to evaluate as many functions as possible while
      minimizing testing time and the professional expertise needed in the test
      setting. The assessment of children 4 through 16 years of age includes 10
      performance-based tests to evaluate key functions within the cognitive, motor,
      and sensory domains analogous to functions affected by neurotoxic chemicals in
      adults. In all age groups, it is crucial to also assess family, cultural,
      economic, and other potentially confounding variables.

PMID- 8866535
TI  - A comparison of NES2 and traditional neuropsychological tests in a neurologic
      patient sample.
AB  - The Neurobehavioral Evaluation System (NES), a computer-assisted battery of
      behavioral tests, has been widely used to detect central nervous system
      dysfunction in occupational and environmental settings and has recently been
      adapted for testing of neurological patients. The purpose of the present study
      was to assess the relationship between NES tasks and the traditional
      neuropsychological tests from which many of the NES tests were developed. For
      this purpose, comparisons were made between scores on NES tests and traditional
      neuropsychological tests designed to measure functioning in the same cognitive
      domains in a sample of patients with idiopathic Parkinson's disease (PD). As has
      been found in prior studies with normal subjects, correlations between
      traditional and NES2 tests varied from low to moderate. Correlations tended to be
      low when the modality of stimulus presentation or responses was different in the
      NES tests from the traditional tasks (e.g., verbal rather than visual) or when
      divergent and highly specific cognitive functions were being measured by the
      tests.

PMID- 8866536
TI  - Validation of the NES2 in patients with neurologic disorders.
AB  - Performance on the Neurobehavioral Evaluation System (NES) has been demonstrated
      to be affected by exposure to a variety of neurotoxicants. However, the relation
      of NES subtests to CNS function has not yet been documented in patients diagnosed
      with neurologic disorders known to implicate specific brain substrates. A
      validation study of the NES2 was carried out in patients with multiple sclerosis
      (MS) and Parkinson's disease (PD), disorders exhibiting neuropathology at loci
      (white matter in MS, basal ganglia in PD) believed to be the sites of action of
      several known neurotoxicants. The results indicated that performance on certain
      NES2 subtests was affected in expected ways in both types of patients. However,
      performance on many more subtests was impaired, relative to controls, in MS than
      in PD. The relative insensitivity to PD suggests that expansion and refinement of
      the battery are required if it is to serve well in detecting the effects of
      toxicants in subjects without frank physical symptoms. These are the goals of a
      new version of the instrument currently under development (NES3).

PMID- 8866537
TI  - Organophosphates: the relationship between chronic and acute exposure effects.
AB  - The relationship between chronic (nonreversing) neuropsychological effects and
      acute exposure effects was investigated in 77 organophosphate exposed male sheep
      dippers. Acute exposure effects were assessed prospectively using a purpose
      constructed symptoms questionnaire administered pre-, and 24 h postexposure.
      Urine was analysed for dialkylphosphate levels to confirm recent exposure.
      Chronic effects were assessed in a cross-sectional neuropsychological study in
      the absence of recent exposure using computerised neuropsychological tests, the
      General Health Questionnaire, and the Subjective Memory Questionnaire. Simple
      correlation and multiple linear regression analyses (adjusting for confounders)
      were used to assess relationships between the change in total symptom reporting
      from baseline to 24 h after exposure and chronic effect outcomes. There was no
      evidence of any association between reported symptom levels and chronic
      neuropsychological effects. This suggests that chronic effects of OP exposure
      appear to occur independently of symptoms that might immediately follow acute OP
      exposure. This has implications for exposure control: individuals may experience
      chronic effects without the benefit of earlier warning signs of toxic effects
      during acute exposures.

PMID- 8866538
TI  - Behavioral effects of exposure to organic solvents in carpet layers.
AB  - Carpet layers and age-matched controls were investigated both at the beginning of
      a working day and at the end with four subtests of a neuropsychological test
      battery (NES2). Exposure to toluene, cyclohexane, ethyl acetate, and heptane was
      measured with personal air sampling methods. One group of carpet layers used
      water-based adhesives (WBA) on the day the investigation took place and the other
      group used contact adhesives (CA) on that day. The WBA group was exposed
      primarily to toluene, and the CA group was exposed to other solvents as well.
      Initial (before work) differences in neuropsychological scores between all
      exposed workers and controls could be attributed to differences in education, the
      carpet layers being somewhat higher educated. No differences were found between
      the solvent-exposed and control groups that would suggest persistent effects of
      chronic solvent exposures. The improvement in test scores over the day was the
      same in both groups. However, evidence for exposure-related changes in test
      scores over the day were found within the exposed group.

PMID- 8866539
TI  - Neurobehavioral effects of occupational exposure to low-level styrene.
AB  - Eighty-six workers in six fiberglass-reinforced plastics manufacturing plants in
      Taiwan were given a detailed evaluation including medical and occupational
      questionnaires, symptom questionnaires, blood sampling, and neurobehavioral
      tests, including cognitive performance, vibratory perception threshold, and
      thermal perception threshold. A Chinese version of cognitive tests modified from
      the Neurobehavioral Evaluation System 2 was applied. Forty-one workers directly
      exposed to styrene at the mean concentration of 22 ppm are compared with 45
      workers not subject to styrene exposure. Multiple linear regression analysis
      controlling for age, sex, education, and alcohol intake revealed significant
      associations between styrene exposure and responses in some neuropsychologic
      measurements. No acute or chronic symptom had significant correlation with
      styrene exposure. Among the neurobehavioral tests, only the continuous
      performance test and vibration threshold were significantly and adversely
      affected in workers exposed to styrene. Significant changes in the central and
      peripheral nervous system were thus detected at a mean styrene exposure of 22
      ppm.

PMID- 8866540
TI  - Long-term cognitive sequelae of solvent intoxication.
AB  - Memory problems lasting 8 months have previously been described for a small group
      of female solvent workers following an accidental workplace solvent intoxication.
      Three years after the intoxication the presence of longer-term residual
      impairment of cognitive functions was evaluated. The major residual difficulty
      uncovered related to the speed of processing linguistic material, with workers
      showing slower verification on tasks probing syntactic and semantic reasoning
      within the context of relatively unimpaired response execution speeds. Of
      particular interest was the intoxicated workers' difficulty with the conceptually
      more complex negative syntactic reasoning problems. This difficulty was also
      shared by solvent workers who were not involved in that accidental intoxication.
      In addition, decision fatigue was observed following prolonged responding in a
      continuous choice reaction time task, although ability to maintain vigilance and
      concentration were unaffected. Taken together, these findings indicate that a
      single solvent intoxication can give rise to long-term cognitive sequelae in
      solvent workers.

PMID- 8866541
TI  - Reaction time changes in workers exposed to lead.
AB  - This article provides a detailed examination of lead workers' reaction times to
      elucidate the underlying basis for the slowing found. Seventy workers, classified
      as either low, medium, or high lead exposed, completed a five-choice reaction
      time task using response-stimulus intervals (RSIs) between 0 and 4 s. Performance
      was assessed by analysing the distributional properties of correct reaction
      times. The effect of lead on movement time was constant across the entire
      movement time distribution and thus simply characteristic of slowed motor
      reaction time. By contrast, the effect of lead on decision time became
      increasingly evident at higher points in the percentile distribution,
      particularly at the shortest RSIs. This suggests that decision slowing is due to
      central, not peripheral, factors and is consistent with alternative analyses
      showing that the incidence of decision gaps also provide a sensitive indicator of
      lead effects. Subsidiary analyses showed that movement and decision slowing was
      correlated solely with levels of blood lead, but not with zinc protoporphyrin or
      urinary ALA levels.

PMID- 8866542
TI  - SPES: a psychological test system to diagnose environmental hazards. Swedish
      Performance Evaluation System.
AB  - The effects of unfavorable work environmental conditions can be studied using
      psychological performance measures and subjective ratings of mood and symptoms.
      In the present article the rationale for such investigations is discussed, and
      the computerized performance evaluation system developed at the Swedish National
      Institute of Occupational Health is presented. The background and the research
      experience leading to the system's development are described, and references to
      the numerous empirical studies demonstrating its applicability to different
      research objectives are given. Also included is information regarding the
      technical requirements for running the SPES tests.

PMID- 8866543
TI  - The Automated Cognitive Test (ACT) system.
AB  - The ACT system is a key-press, menu-driven system for selecting, administering,
      and storing raw data from a series of specially designed psychological tasks.
      Associated task analysis programs process the raw data and store the resulting
      summary data for later statistical analysis. The system utilizes a cognitive
      approach to assessments of marginal toxicity by employing multiple performance
      parameters to specify a profile of deficits that, on the basis of a task's
      internal structure, can be related to functionally discrete cognitive systems.
      The tasks have been developed from a consideration of current cognitive theory
      and the areas of cognition include those of learning, memory, attention,
      reasoning, verbal, and spatial abilities. The ACT system is described in terms of
      its four major components: the cognitive tasks, the stimulus materials, the
      analysis methods, and the process of saving and combining summary data into files
      suitable for transfer to statistical analysis programs. The system thus automates
      the data collection to statistical analysis process.

PMID- 8866544
TI  - CANTAB battery: proposed utility in neurotoxicology.
AB  - The CANTAB battery was developed for the assessment of cognitive deficits in
      humans with neurodegenerative diseases or brain damage. It consists of a series
      of interrelated computerized tests of memory, attention, and executive function,
      administered via a touch sensitive screen. It allows a decomposition of complex
      tasks commonly used in clinical assessment into their cognitive components and
      enables the extrapolation of findings from the animal literature. Tests include
      versions of the Wisconsin Card-Sorting Test and the Tower and London and also the
      Delayed Matching-to-Sample test, widely used in monkeys for visual recognition
      memory. The tests are constructed in such a way that they may be given to animals
      (monkeys) with minimal change. The nonverbal nature of the CANTAB tests makes
      them largely language independent and culture free. CANTAB has been standardized
      on a large, predominantly elderly, population and validated in neurosurgical
      patients as well as in patients with basal ganglia disorders, Alzheimer's
      disease, depression, and schizophrenia. In addition, CANTAB has been used to
      evaluate: a) the therapeutic effects of dopaminergic and cholinergic medication
      in neurodegenerative disease; b) cognition in 5-11-year-old normal, learning
      disabled, and autistic children; c) deficits in patients with HIV infection; and
      d) early, asymptomatic Huntington's disease. The latter illustrate its usefulness
      in early identification of progressive disorders. It is suggested that the
      battery should have particular utility across a wide range of age and
      intelligence in longitudinal assessment after exposure to toxicants, and allow
      meaningful comparison with experimental studies of toxic effects in other
      species.

PMID- 8866545
TI  - Acute mercury intoxication examined with coordination ability and tremor.
AB  - At a mercury spill, several workers were exposed to mercury vapour concentrations
      up to 0.15 mg/m3. Two weeks after, 38 exposed workers were examined. Fourteen had
      a Hg in urine concentration above 25 nmol/l. Two exposed groups (n = 7) and an
      unexposed control group (n = 15) were formed, based on Hg in urine: a HI group
      with mean = 106.5 nmol/l (range: 49.5-249); a LO group with mean = 35.2 nmol/l
      (range: 28.8-48.0), and control group with mean = 10.5 nmol/l (range: 4.5-14.1).
      The groups were reexamined 3 and 16 months later. The groups were examined with
      two computer-based portable test systems. CATSYS quantifies hand
      pronation/supination, finger tapping, and reaction time. TREMOR records and
      analyses tremor at the finger tips. The results showed reduced coordination
      ability in the HI group at the first examination compared to the control group.
      Tremor intensity was very high in the HI group and decreased only slightly during
      the follow-up period. The study indicates that quantification of coordination
      ability and tremor intensity can be used within occupational medicine for the
      assessment of the impact of acute mercury intoxication.

PMID- 8866546
TI  - Computer-administration of questionnaires: a health screening system (HSS)
      developed for veterans.
AB  - The introduction of microcomputers in psychological research has spawned a
      burgeoning number of tests of psychological or behavioral function, but few
      computerized systems for administering questionnaires have been developed. A
      Health Screening System (HSS) is described that combines the benefits of the
      paper-and-pencil format (e.g., convenient navigation within test questions) and
      the added benefits of computer-implementation (e.g., efficiency, automated
      scoring). The HSS features; a) appealing test appearance (e.g., text in large
      size fonts, color backgrounds); b) clear wording of tests and instructions
      (identical wording as original tests except when clarity is served by changes);
      c) limiting need for Examiner-Subject interaction (e.g., continuously available
      on-line training, navigation within test questions, answer review capability,
      durable 9-button response unit); d) options (e.g., question skipping, spoken
      instructions, test questions, and answers on command); e) modification
      capabilities (e.g., color, text, test layout editing, control of test order,
      automated breaks, addition of tests to system); and f) extras (e.g., kernel of
      main instruction on each test screen, digitized video, audio message from
      Examiner in training, copyright notification on each screen, raw and summary data
      outputs in spreadsheet formal). Ten HSS tests were administered to 22 US military
      veterans, who took slightly longer to complete them than did 10 veterans who were
      administered the same tests in their original paper-and-pencil format. User
      reaction to the computerized HSS was positive.

PMID- 8866547
TI  - Leptin: the tale of an obesity gene.

PMID- 8866548
TI  - Disturbed development of the preimplantation embryo in the insulin-dependent
      diabetic BB/E rat.
AB  - Although improved regulation of maternal IDDM during pregnancy has resulted in a
      major fall in the stillbirth rate, the rates for other problems, such as
      spontaneous preterm labor, fetuses small for gestational age, congenital
      malformation, and the incidence of large placentas, remain raised. This has
      suggested the possibility that the damaging effect of conventionally treated but
      poorly regulated IDDM may operate primarily at the earliest stages of gestation,
      even before the diagnosis of pregnancy has been made. This study shows that
      spontaneous autoimmune IDDM in the Bio Breeding/Edinburgh (BB/E) rat is
      associated with severe disturbance in the development of the preimplantation
      embryo in a majority of pregnancies, as indicated by a fivefold increase in the
      incidence of degenerate fragmented embryos and a 33% reduction in the number of
      expanded blastocysts and in those blastocysts that reach the expanded stage a 20%
      cellular deficit in the inner-cell mass without any change in trophectoderm cell
      number. In addition, we find that blastocysts removed from diabetic rats and
      cultured in vitro for 24 h show no sign of "catch-up" growth of the inner-cell
      mass, although under these conditions, the trophectoderm exhibits a 25% cellular
      accretion. It is tempting to speculate that these phenomena are a presage of the
      characteristic combination of fetal growth retardation and large placentas, which
      are a feature of both BB/E rat and human IDDM pregnancy.

PMID- 8866549
TI  - Evidence for dissociation of insulin stimulation of blood flow and glucose uptake
      in human skeletal muscle: studies using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose,
      and positron emission tomography.
AB  - We determined the effect of insulin on muscle blood flow and glucose uptake in
      humans using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and positron
      emission tomography (PET). Femoral muscle blood flow was measured in 14 healthy
      volunteers (age 34 +/- 8 years, BMI 24.6 +/- 3.4 kg/m2 [means +/- SD]) before and
      at 75 min during a 140-min high-dose insulin infusion (serum insulin 2,820 +/-
      540 pmol/l) under normoglycemic conditions. A dynamic scan of the femoral region
      was performed using PET for 6 min after injection of [15O]H2O to determine the
      15O concentration in tissue. Regional femoral muscle blood flow was calculated
      using an autoradiographic method from the dynamic data obtained with PET and
      [15O]H2O. Femoral muscle glucose uptake was measured during hyperinsulinemia
      immediately after the flow measurement using PET-derived [18F]FDG kinetics and a
      three-compartment model. Whole-body glucose uptake was quantitated using the
      euglycemic insulin clamp technique. In the basal state, 84 +/- 8% of blood flow
      was confined to skeletal muscle. Insulin increased leg blood flow from 29 +/- 14
      to 54 +/- 29 ml x kg-1 leg x min-1 (P < 0.001) and muscle flow from 31 +/- 18 to
      58 +/- 35 ml x kg-1 muscle x min-1 (P < 0.005). Under insulin-stimulated
      conditions, 81 +/- 8% of blood flow was in muscle tissue (NS versus basal).
      Skeletal muscle explained 70 +/- 25% of the increase in leg blood flow. No
      correlation was observed between blood flow and glucose uptake when analyzed
      individually in identical regions of interest within femoral muscles. These data
      demonstrate that skeletal muscle accounts for most of the insulin-induced
      increase in blood flow. Insulin-stimulated rates of blood flow and glucose uptake
      do not colocalize in the same regions of muscle tissue, suggesting that insulin's
      hemodynamic and metabolic effects are differentially regulated.

PMID- 8866550
TI  - The human glucokinase gene beta-cell-type promoter: an essential role of insulin
      promoter factor 1/PDX-1 in its activation in HIT-T15 cells.
AB  - The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive
      secretion of insulin, and defects of this enzyme can cause NIDDM. As a step
      toward understanding the molecular basis of glucokinase (GK) gene regulation, we
      assessed the structure and regulation of the human GK gene beta-cell-type
      promoter. The results of reporter gene analyses using HIT-T15 cells revealed that
      the gene promoter was comprised of multiple cis-acting elements, including two
      primarily important cis-motifs: a palindrome structure, hPal-1, and the insulin
      gene cis-motif A element-like hUPE3. While both elements were bound specifically
      by nuclear proteins, it was the homeodomain-containing transcription factor
      insulin promoter factor 1 (IPF1)/STF-1/PDX-1 that bound to the hUPE3 site: IPF1,
      when expressed in CHO-K1 cells, became bound to the hUPE3 site and activated
      transcription. An anti-IPF1 antiserum used in gel-mobility shift analysis
      supershifted the DNA protein complex formed with the hUPE3 probe and nuclear
      extracts from HIT-T15 cells, thus supporting the involvement of IPF1 in GK gene
      activation in HIT-T15 cells. In contrast to the insulin gene, however, neither
      the synergistic effect of the Pan1 expression on the IPF1-induced promoter
      activation nor the glucose responsiveness of the activity was observed for the GK
      gene promoter. These results revealed some conservative but unique features for
      the transcriptional regulation of the beta-cell-specific genes in humans. Being
      implicated in insulin and GK gene regulations as a common transcription factor,
      IPF1/STF-1/PDX-1 is likely to play an essential role in maintaining normal beta
      cell functions.

PMID- 8866551
TI  - Glycation of insulin in the islets of Langerhans of normal and diabetic animals.
AB  - The glycation of immunoreactive insulin (IRI) was assessed in extracts of
      pancreas and islets from control and hyperglycemic animal models. Glycated and
      nonglycated IRI were separated by affinity chromatography and quantified by
      radioimmunoassay. Hydrocortisone-treated Wistar rats (80 mg x kg-1 x day-1 and
      obese hyperglycemic (ob/ob) mice showed significant increases in plasma glucose
      (P < 0.001), percentage glycated hemoglobin (P < 0.001), plasma IRI (P < 0.01),
      and total pancreatic IRI content (P < 0.01), compared with their respective
      controls. These diabetic groups also demonstrated significant increases (P <
      0.05) in the percentage of glycated pancreatic IRI above the controls.
      Streptozotocin-treated (200 mg/kg) Swiss TO mice exhibited significant increases
      in plasma glucose (P < 0.001), glycated hemoglobin (P < 0.001), and percentage
      glycated pancreatic IRI (P < 0.05), compared with untreated controls, despite a
      marked decrease in both plasma IRI (P < 0.001) and total pancreatic IRI content
      (P < 0.001). Significant elevations in the percentage of glycated IRI were also
      observed in islets isolated from obese hyperglycemic (ob/ob) mice (P < 0.001),
      compared with islets from lean controls, and when lean mouse islets were cultured
      in hyperglycemic media for 24 h (33.3 vs. 5.6 mmol/l D-glucose; P < 0.001). The
      contribution of glycated plus nonglycated insulin and proinsulin to the total IRI
      was estimated in lean and obese mouse pancreatic extracts following high
      performance liquid chromatography separation. The contribution of proinsulin to
      the total IRI was approximately 10%. Proinsulin represented 27-28% of the total
      glycated IRI. These data indicate that the glycation of insulin and proinsulin
      occurs within the pancreatic islets and is elevated in both insulin-deficient and
      insulin-resistant diabetic animal models.

PMID- 8866552
TI  - Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show
      decreased occurrence of malformations in offspring.
AB  - The increased incidence of congenital malformations in diabetic pregnancy may be
      associated with an excess of free oxygen radicals in the embryo. We have
      previously blocked the dysmorphogenesis of rat embryos exposed to high glucose
      and beta-hydroxybutyrate concentrations in vitro by increasing the antioxidant
      capacity of the conceptus. In the present study, we attempted to diminish the
      teratogenic process in vivo in a rat model of diabetic pregnancy. Thus, pregnant
      diabetic and normal rats were fed either a standard diet or a diet enriched with
      1% of the antioxidant butylated hydroxytoluene (BHT). The fetuses of the diabetic
      rats were smaller than the fetuses of the normal rats (body weight 2.70 g vs.
      3.68 g) when the mothers were fed a standard diet. The BHT diet increased the
      fetal weight in the offspring of diabetic rats (3.17 g), with no change in
      fetuses of the normal rats (3.65 g). The placentas of diabetic rats were heavier
      than the placentas of normal rats; this difference was not present in the BHT-fed
      rats. The BHT treatment had no effect on the rate of resorptions, which was
      increased in the diabetic rats compared with the normal rats. In contrast, the
      increased rate of congenital malformations in the offspring of diabetic rats
      (19%), compared with that in the normal rats (0%), was markedly decreased by the
      BHT diet (2.3%). No malformations were found in the normal rats treated with BHT.
      These data support the notion that an excess of free oxygen radicals in the
      embryo contributes to the teratogenic process of diabetic pregnancy and, thus,
      suggest an area for future preventive therapeutic treatment.

PMID- 8866553
TI  - Altered insulin secretory responses to glucose in diabetic and nondiabetic
      subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome
      12.
AB  - One form of maturity-onset diabetes of the young (MODY) results from mutations in
      a gene, designated MODY3, located on chromosome 12 in band q24. The present study
      was undertaken to define the interactions between glucose and insulin secretion
      rate (ISR) in subjects with mutations in MODY3. Of the 13 MODY3 subjects, six
      subjects with normal fasting glucose and glycosylated hemoglobin and seven
      overtly diabetic subjects were studied as were six nondiabetic control subjects.
      Each subject received graded intravenous glucose infusions on two occasions
      separated by a 42-h continuous intravenous glucose infusion designed to prime the
      beta-cell to secrete more insulin in response to glucose. ISRs were derived by
      deconvolution of peripheral C-peptide levels. Basal glucose levels were higher
      and insulin levels were lower in MODY3 subjects with diabetes compared with
      nondiabetic subjects or with normal healthy control subjects. In response to the
      graded glucose infusion, ISRs were significantly lower in the diabetic subjects
      over a broad range of glucose concentrations. ISRs in the nondiabetic MODY3
      subjects were not significantly different from those of the control subjects at
      plasma glucose levels <8 mmol/l. As glucose rose above this level, however, the
      increase in insulin secretion in these subjects was significantly reduced.
      Administration of glucose by intravenous infusion for 42 h resulted in a
      significant increase in the amount of insulin secreted over the 5-9 mmol/l
      glucose concentration range in the control subjects and nondiabetic MODY3
      subjects (by 38 and 35%, respectively), but no significant change was observed in
      the diabetic MODY3 subjects. In conclusion, in nondiabetic MODY3 subjects insulin
      secretion demonstrates a diminished ability to respond when blood glucose exceeds
      8 mmol/l. The priming effect of glucose on insulin secretion is preserved. Thus,
      beta-cell dysfunction is present before the onset of overt hyperglycemia in this
      form of MODY. The defect in insulin secretion in the nondiabetic MODY3 subjects
      differs from that reported previously in nondiabetic MODY1 or mildly diabetic
      MODY2 subjects.

PMID- 8866554
TI  - Responses of leptin to short-term fasting and refeeding in humans: a link with
      ketogenesis but not ketones themselves.
AB  - We investigated the response of leptin to short-term fasting and refeeding in
      humans. A mild decline in subcutaneous adipocyte ob gene mRNA and a marked fall
      in serum leptin were observed after 36 and 60 h of fasting. The dynamics of the
      leptin decline and rise were further substantiated in a 6-day study consisting of
      a 36-h baseline period, followed by 36-h fast, and a subsequent refeeding with
      normal diet. Leptin began a steady decline from the baseline values after 12 h of
      fasting, reaching a nadir at 36 h. The subsequent restoration of normal food
      intake was associated with a prompt leptin rise and a return to baseline values
      24 h later. When responses of leptin to fasting and refeeding were compared with
      that of glucose, insulin, fatty acids, and ketones, a reverse relationship
      between leptin and beta-OH-butyrate was found. Consequently, we tested whether
      the reciprocal responses represented a causal relationship between leptin and
      beta-OH-butyrate. Small amounts of infused glucose equal to the estimated
      contribution of gluconeogenesis, which was sufficient to prevent rise in
      ketogenesis, also prevented a fall in leptin. The infusion of beta-OH-butyrate to
      produce hyperketonemia of the same magnitude as after a 36-h fast had no effect
      on leptin. The study indicates that one of the adaptive physiological responses
      to fasting is a fall in serum leptin. Although the mediator that brings about
      this effect remains unknown, it appears to be neither insulin nor ketones.

PMID- 8866555
TI  - Muscle subcellular localization and recruitment by insulin of glucose
      transporters and Na+-K+-ATPase subunits in transgenic mice overexpressing the
      GLUT4 glucose transporter.
AB  - Insulin-stimulated glucose uptake in skeletal muscle is mediated through the
      GLUT4 glucose transporter. Transgenic (TG) mice overexpressing human GLUT4 in
      skeletal muscle show an increased ability to handle a glucose load. Here, the
      participation of the overexpressed GLUT4 in the response to insulin was examined.
      In TG mouse muscle, the GLUT4 protein content was 10-fold higher in crude
      membrane (CM), sevenfold higher in internal membrane (IM), and 15-fold higher in
      a plasma membrane (PM)-rich fraction, relative to non-TG littermates. This
      suggested partial saturation of the normal sorting mechanisms. The distribution
      and abundance of the GLUT1 glucose transporter was not affected. Insulin
      injection (4.3 U/kg body wt) increased GLUT4 in the PM-rich fraction; the
      increase was threefold higher in TG than in non-TG mice. Insulin decreased the
      GLUT4 content of the IM in both animal groups and of a second, heavier
      intracellular membrane fraction only in TG mice. The net content of Na+-K+-pump
      subunits was 40-65% lower in CM from TG compared with non-TG littermates. In
      spite of this, insulin caused a three- to sixfold higher translocation of the
      alpha2 and beta1 subunits of the Na+-K+-pump in TG compared with non-TG animals.
      The results suggest that overexpression of GLUT4 confers to the muscle increased
      ability to translocate subunits of the Na+-K+-pump either as a direct consequence
      of the recruitment of glucose transporters or as an adaptation to the more
      demanding metabolic state.

PMID- 8866556
TI  - Normalization of insulin responses to glucose by overnight infusion of glucagon
      like peptide 1 (7-36) amide in patients with NIDDM.
AB  - Glucagon-like peptide 1 (GLP-1) is a natural enteric incretin hormone, which is a
      potent insulin secretogogue in vitro and in vivo in humans. Its effects on
      overnight glucose concentrations and the specific phases of insulin response to
      glucose and nonglucose secretogogues in subjects with NIDDM are not known. We
      compared the effects of overnight intravenous infusion of GLP-1 (7-36) amide with
      saline infusion, on overnight plasma concentrations of glucose, insulin, and
      glucagon in eight subjects with NIDDM. The effects on basal (fasting) beta-cell
      function and insulin sensitivity were assessed using homeostasis model assessment
      (HOMA) and compared with seven age- and weight-matched nondiabetic control
      subjects. The GLP-1 infusion was continued, and the first- and second-phase
      insulin responses to a 2-h 13 mmol/l hyperglycemic clamp and the insulin response
      to a subsequent bolus of the nonglucose secretogogue, arginine, were measured.
      These were compared with similar measurements recorded after the overnight saline
      infusion and in the control subjects who were not receiving GLP-1. The effects on
      stimulated beta-cell function of lowering plasma glucose per se were assessed by
      a separate overnight infusion of soluble insulin, the rate of which was adjusted
      to mimic the blood glucose profile achieved with GLP-1. Infusion of GLP-1
      resulted in significant lowering of overnight plasma glucose concentrations
      compared with saline, with mean postabsorptive glucose concentrations (2400-0800)
      of 5.6 +/- 0.8 and 7.8 +/- 1.4 mmol/l, respectively (P < 0.0002). Basal beta-cell
      function assessed by HOMA was improved from geometric mean (1 SD range), 45% beta
      (24-85) to 91% beta (55-151) by GLP-1 (P < 0.0004). First-phase incremental
      insulin response to glucose was improved by GLP-1 from 8 pmol/l (-8-33) to 116
      pmol/l (12-438) (P < 0.005), second-phase insulin response to glucose from 136
      pmol/l (53-352) to 1,156 pmol/l (357-3,748) (P < 0.0002), and incremental insulin
      response to arginine from 443 pmol/l (172-1,144) to 811 pmol/l (272-2,417) (P <
      0.002). All responses on GLP-1 were not significantly different from nondiabetic
      control subjects. Reduction of overnight glucose by exogenous insulin did not
      improve any of the phases of stimulated beta-cell function. Prolonged intravenous
      infusion of GLP-1 thus significantly lowered overnight glucose concentrations in
      subjects with NIDDM and improved both basal and stimulated beta-cell function to
      nondiabetic levels. It may prove to be a useful agent in the reduction of
      hyperglycemia in NIDDM.

PMID- 8866557
TI  - Inhibition of mitochondrial complex I may account for IDDM induced by
      intoxication with the rodenticide Vacor.
AB  - Human intoxication with the rodenticide Vacor [N-3-pyridylmethyl-N'-p-nitrophenyl
      urea or 1-(4-nitrophenyl)-3-(3-pyridylmethyl) urea] induces acute IDDM. We report
      here that Vacor specifically inhibits the NADH:ubiquinone reductase activity of
      complex I in mammalian mitochondria. The activity of other respiratory enzymes of
      mitochondria is unaffected by Vacor at concentrations that completely inhibit the
      redox and energetic function of complex I. Vacor inhibition of complex I activity
      quantitatively correlates with the inhibition of insulin release in insulinoma
      cells and pancreatic islets and is also consistent with the doses reported in
      cases of human poisoning. These results indicate that the toxic and diabetogenic
      action of Vacor primarily derives from the inhibition of mitochondrial
      respiration of NAD-linked substrates in the high-energy demanding cells of the
      pancreatic islets. This newly identified mechanism of the pathological effects
      resulting from Vacor intoxication could constitute a paradigm in which to
      understand environmental or metabolic causes of IDDM.

PMID- 8866558
TI  - Genetic control of giant perivascular space formation in the thymus of NOD mice.
AB  - The immune system of NOD mice exhibits several anomalies, one being the
      intrathymic formation of giant perivascular spaces (PVSs) filled with mature
      thymocytes and some B-cells, intermingled within a network of extracellular
      matrix. The abnormal retention of thymocytes on their way to the periphery could
      have a profound impact on the nature of the exported cells and the regulation of
      autoimmune events. In the present study, we evaluated the appearance of this
      defect into F1 hybrids, the association with some of the known diabetes
      susceptibility loci (Idd genes) in a panel of NOD and reciprocal C57BL congenic
      strains, and the relative contribution of epithelial versus hematopoietic stroma.
      The analysis of F1 hybrid thymuses reveals a dominant expression of thymic giant
      PVS that is only marginally influenced by the outcross strain. Moreover, giant
      PVS expression in major histocompatibility complex (MHC) and Idd congenic mice is
      determined by the genetic background. All of the NOD congenics express the
      anomaly, irrespective of the Idd resistance alleles that have been introgressed,
      whereas none of the C57BL congenic mice present abnormal PVS. Finally, the
      expression of giant PVS in parental --> F1 bone marrow chimeras is predominantly
      controlled by the thymic NOD-derived hematopoietic microenvironment. In
      conclusion, the giant PVS formation in the NOD mouse thymus is a dominantly
      inherited anomaly associated with hematopoietic-derived tissue and with non-MHC
      genes. The exact contribution of PVS to the autoimmune process remains to be
      definitively established.

PMID- 8866559
TI  - Beta-cell growth and mass are preserved in long-term syngeneic islet
      transplantation in streptozocin-induced diabetic Lewis rats.
AB  - We determined beta-cell replication and mass in basal and stimulated conditions
      in long-term transplanted islets. Three groups of streptozocin-induced diabetic
      Lewis rats were transplanted with 1,000 islets (500 islets under left and right
      kidney capsules). At 2 (Tx-2), 5 (Tx-5), or 9 (Tx-9) months after
      transplantation, one of the two grafts (basal) was harvested; 14 days later, the
      contralateral graft (stimulated) was also harvested. Normoglycemia was achieved
      and maintained in all transplanted rats, although the capacity to respond to a
      glucose challenge deteriorated slightly 9 months after transplantation. Beta-cell
      replication remained stable in Tx-2, Tx-5, and Tx-9 basal grafts and was similar
      to replication in a control group of nontransplanted rats (0.28 +/- 0.06%);
      replication increased in Tx-2 (0.90 +/- 0.23%, P < 0.05) and Tx-9 (0.72 +/-
      0.09%, P < 0.05) stimulated grafts. Beta-cell mass in basal grafts was similar to
      the initially transplanted mass (1.24 +/- 0.06 mg) and increased in stimulated
      grafts in Tx-2 (1.91 +/- 0.38 mg, P < 0.05) and Tx-5 (1.73 +/- 0.27 mg, P = 0.01)
      groups, compared with basal grafts, and in Tx-2 and Tx-9 groups (1.92 +/- 0.30
      mg, P < 0.05), compared with initially transplanted mass. Therefore, beta-cell
      replication and mass were preserved up to 9 months after syngeneic
      transplantation, and beta-cells maintained the capacity to respond to increased
      metabolic demand, suggesting that replication is not a limiting factor in the
      survival of transplanted islets.

PMID- 8866560
TI  - Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non
      Hispanic white men and women. The Insulin Resistance and Atherosclerosis Study.
AB  - Increased abdominal obesity has been related to lower insulin sensitivity (SI),
      independent of overall obesity, but it has been suggested that this relationship
      may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study
      (IRAS), SI was estimated using a minimal model analysis of the frequently sampled
      intravenous glucose tolerance test in 1,625 men and women aged 40-69 years.
      Subjects included African-Americans, Hispanics, and non-Hispanic whites from
      Oakland and Los Angeles, CA, San Antonio, TX, and the San Luis Valley, CO.
      Minimum waist circumference was significantly (P = 0.0001) associated with SI
      after adjusting for age, sex, height, BMI, glucose tolerance status, ethnicity,
      and clinic. This relationship was significantly (P = 0.0001) stronger in subjects
      with normal glucose tolerance (NGT) (beta = -0.030, P = 0.0001) than in those
      with impaired glucose tolerance (IGT) (beta = -0.010, P = 0.02; NIDDM: beta = 
      0.013, P = 0.0001). There were no significant ethnic differences in effect size
      across the spectrum of glucose tolerance. Waist circumference was also positively
      related to fasting insulin, an indirect measure of insulin sensitivity, in NGT (P
      = 0.0001), IGT (P = 0.0003), and NIDDM (P = 0.0002). The waist-fasting insulin
      relationship was significantly weaker in African-Americans, relative to non
      Hispanic whites, in NGT and IGT (tests of statistical interaction: P = 0.04 and P
      = 0.02, respectively). In general, these patterns were similar in models
      specifying waist-to-hip ratio (WHR), rather than waist circumference, as the
      independent variable. While some ethnic variability exists, a negative
      relationship between abdominal obesity and insulin sensitivity was confirmed for
      all three ethnic groups across the spectrum of glucose tolerance.

PMID- 8866561
TI  - Troglitazone inhibits fatty acid oxidation and esterification, and
      gluconeogenesis in isolated hepatocytes from starved rats.
AB  - The effects of troglitazone and pioglitazone on glucose and fatty acid metabolism
      were studied in hepatocytes isolated from 24-h-starved rats. These
      thiazolidinediones inhibited long-chain fatty acid (oleate) oxidation and
      produced a very oxidized mitochondrial redox state. By contrast,
      thiazolidinediones did not affect the rate of medium-chain fatty acid (octanoate)
      oxidation or the activity of mitochondrial carnitine palmitoyltransferase (CPT)
      I. Thiazolidinediones inhibited selectively triglyceride synthesis but not
      phospholipid synthesis. The combined inhibition of oleate oxidation and
      esterification by troglitazone was due to a noncompetitive inhibition of
      mitochondrial and microsomal long-chain acyl-CoA synthetase (ACS) activities. It
      was suggested that troglitazone must be metabolized into its sulfo-conjugate
      derivative in liver cells to inhibit mitochondrial and microsomal ACS activities.
      Thiazolidinediones inhibited glucose production from lactate/pyruvate or from
      alanine. Analysis of gluconeogenic metabolite concentrations suggested that
      troglitazone would inhibit gluconeogenesis at the level of pyruvate carboxylase
      and glyceraldehyde-3-phosphate dehydrogenase reactions. It was concluded that 1)
      at a similar concentration, troglitazone was more efficient than pioglitazone to
      inhibit fatty acid metabolism and gluconeogenesis and 2) the inhibition of
      gluconeogenesis by troglitazone could be the result of the inhibition of long
      chain fatty acid oxidation (decrease in acetyl-CoA, NADH-to-NAD+, and ATP-to-ADP
      ratios).

PMID- 8866562
TI  - Regulation of rat liver glucose-6-phosphatase gene expression in different
      nutritional and hormonal states: gene structure and 5'-flanking sequence.
AB  - The mRNA level of the catalytic subunit of rat liver glucose-6-phosphatase (Glu-6
      Pase) was regulated by hormones commensurate with activity changes in vivo.
      Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both
      mRNA levels and activities of the enzyme are low in the fed and refed state where
      insulin levels are elevated. Insulin administration to diabetic rats also
      decreases levels of mRNA and Glu-6-Pase activity. Insulin at a concentration of 1
      nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6
      Pase message levels in FAO hepatoma cells. The stimulatory response to
      glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after
      hormone addition (respectively 1.6- and 3.3-fold). 8-(4-chlorophenylthio)-cAMP
      (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The
      gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons.
      The exon-intron structure is completely conserved when compared with the mouse
      and human genes. A 0.5-kb 3'-untranslated region, which is present in rat and
      mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here,
      indicating the possible duplication of either the terminal fifth exon or the
      entire gene. The promoter region contains a consensus core CCAAT element at
      position -207 and a TATAAA at position -31. Several possible response elements
      have been identified in the 5'-flanking region (from a HindIII site at position 
      1641). A consensus glucocorticoid response element is located at base pair -1552,
      a 9/10 match of the insulin response sequence is located at position -1449, and a
      7/8 match of the cAMP response element is located at position -164.

PMID- 8866563
TI  - Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function
      in women at high risk for NIDDM.
AB  - We conducted a randomized placebo-controlled study to determine the effects of
      the thiazolidinedione compound troglitazone on whole-body insulin sensitivity
      (SI), pancreatic beta-cell function, and glucose tolerance in 42 Latino women
      with impaired glucose tolerance (IGT) and a history of gestational diabetes
      mellitus (GDM), characteristics that carry an 80% risk of developing NIDDM within
      5 years. After baseline oral (OGTT) and intravenous (IVGTT) glucose tolerance
      testing, subjects were assigned to take placebo or 200 or 400 mg troglitazone
      daily for 12 weeks (14 subjects per treatment group). An OGTT and IVGTT were
      repeated during the 12th week of treatment. Five subjects failed to complete the
      trial for personal reasons, and medication compliance averaged 90% in the
      remaining subjects, none of whom experienced a serious adverse event. SI,
      calculated by minimal model analysis of IVGTT results, changed by only 4 +/- 14%
      during 12 weeks of placebo administration, but increased 40 +/- 22 and 88 +/- 22%
      above basal during treatment with 200 and 400 mg troglitazone, respectively (P =
      0.01 among groups). Troglitazone administration was also associated with a dose
      dependent reduction in the total insulin area during IVGTTs, which was highly
      significant (P < 0.001), and with a reduction during OGTTs, which approached
      statistical significance (P = 0.09). Glucose tolerance improved slightly in all
      groups, but the magnitude of change did not differ significantly among groups,
      whether it was assessed as the number of subjects who continued to manifest IGT
      at 12 weeks (P = 0.64 among groups), the change in total glucose area during
      OGTTs (P = 0.58), or the change in fractional glucose disappearance rates during
      IVGTTs (P = 0.28). Among the women who received troglitazone, the greatest
      improvement in SI occurred in the women who had the highest diastolic blood
      pressures and the best IVGTT insulin responses during baseline testing. Our
      findings indicate that troglitazone improved whole-body insulin sensitivity and
      lowered circulating insulin concentrations in women with prior GDM who are at
      very high risk for NIDDM. The lack of improvement in glucose tolerance despite
      improved insulin sensitivity may be a manifestation of the beta-cell defect that
      predisposes the women to NIDDM. The overall pattern of response to troglitazone
      in our high-risk patients indicates that the drug is an ideal agent with which to
      test whether the amelioration of insulin resistance can delay or prevent diabetes
      in women with limited beta-cell reserve.

PMID- 8866564
TI  - Plasma leptin levels correlate to islet function independently of body fat in
      postmenopausal women.
AB  - It has previously been demonstrated that plasma leptin correlates to body fat
      content. Increased body fat content is accompanied by low insulin sensitivity,
      which is compensated with increased insulin secretion. We therefore studied
      whether plasma levels of leptin also correlate to insulin secretion and
      sensitivity in humans. Therefore, we examined insulin sensitivity by the
      euglycemic-hyperinsulinemic clamp technique and measured the insulin response to
      intravenous arginine (5 g) at fasting and 14 mmol/l glucose in postmenopausal
      women. Percent body fat content was determined with impedance measurements. Log
      plasma leptin significantly correlated to percent body fat (r = 0.84, P < 0.001).
      In women with normal glucose tolerance (n = 36), partial correlation studies
      controlling for body fat content revealed significant correlations between log
      plasma leptin and fasting insulin levels (r = 0.39, P = 0.029), the insulin
      response to arginine at both glucose levels (r = 0.38 and r = 0.37, P < 0.036 for
      both), and the glucose potentiation of arginine-stimulated insulin secretion (r =
      0.40, P = 0.025). In contrast, in women with impaired glucose tolerance (n = 17),
      these correlations were not significant. Plasma leptin did not correlate with
      insulin sensitivity independently of body fat content. To study whether the
      correlation between leptin and insulin would be explained by insulin stimulating
      leptin secretion, we examined plasma leptin during hyperinsulinemic conditions
      (689 +/- 41 pmol/l), under both euglycemia (5.0 mmol/l, n = 10) and hypoglycemia
      (2.5 mmol/l, n = 7). However, under both these conditions, plasma leptin was
      unaltered. In conclusion, plasma leptin 1) reflects body fat content and 2)
      correlates to insulin secretion independently of percent body fat in
      postmenopausal women with normal glucose tolerance.

PMID- 8866565
TI  - Metabolic consequences of a family history of NIDDM (the Botnia study): evidence
      for sex-specific parental effects.
AB  - Although a strong genetic susceptibility has been established for NIDDM and a
      maternal transmission of the disease predominates in some populations, a
      relationship between parental diabetes status and metabolic abnormalities in
      nondiabetic offspring has not been shown in humans. To address this question, we
      studied 2,152 first-degree relatives of patients with NIDDM (FH+) and 528 age-
      and weight-matched spouses without a family history of NIDDM (FH-) in Western
      Finland (the Botnia study). A subset of the subjects underwent a euglycemic
      insulin clamp combined with indirect calorimetry to measure insulin sensitivity
      and energy expenditure. Despite similar amounts of total body fat, persons with a
      family history of NIDDM had a greater waist-to-hip ratio (WHR) than spouses
      without a family history of diabetes (P < 0.003). They also had a decreased
      resting metabolic rate (P = 0.005), but this difference disappeared when adjusted
      for the difference in WHR. Insulin-stimulated glucose metabolism (P = 0.002),
      particularly nonoxidative glucose metabolism (P = 0.009), was reduced in FH+
      compared with FH- subjects, and this difference remained after adjustment for
      WHR. A parental history of NIDDM influenced the insulin response to the oral
      glucose load, with male offspring of diabetic mothers showing the lowest insulin
      values (P = 0.011). Moreover, a parental effect was also observed on HDL and HDL2
      cholesterol concentrations with female offspring of diabetic mothers showing
      lower values than female offspring of diabetic fathers (both P < 0.002). We
      conclude that abdominal obesity, insulin resistance, and decreased resting
      metabolic rate are characteristic features of first-degree relatives of patients
      with NIDDM and that the decrease in resting metabolic rate is partially related
      to the degree of abdominal obesity. A sex-specific paternal effect was observed
      on insulin and HDL cholesterol concentrations. Therefore, one has to consider the
      possibility of unprecedented maternal or paternal inheritance of different NIDDM
      phenotypes.

PMID- 8866566
TI  - A comparison of the effects of selective increases in peripheral or portal
      insulin on hepatic glucose production in the conscious dog.
AB  - We investigated the mechanisms by which peripheral or portal insulin can
      independently alter liver glucose production. Isotopic ([3-3H]glucose) and
      arteriovenous difference methods were used in conscious overnight-fasted dogs. A
      pancreatic clamp (somatostatin plus basal insulin and basal glucagon infusions)
      was used to control the endocrine pancreas. After a 40-min basal period, a 180
      min experimental period followed in which selective increases in peripheral (PERI
      group, n = 5) or portal-vein (PORT group, n = 5) insulin were induced. In control
      dogs (CONT group, n = 10), insulin was not increased. Glucagon levels were fixed
      in all studies, and basal euglycemia was maintained by peripheral glucose
      infusion in the two experimental groups. In the PERI group, arterial insulin rose
      from 36 +/- 12 to 120 +/- 12 pmol/l, while portal insulin was unaltered. In the
      PORT group, portal insulin rose from 108 +/- 42 to 192 +/- 42 pmol/l, while
      arterial insulin was unaltered. Neither arterial nor portal insulin changed from
      basal in the CONT group. With a selective rise in peripheral insulin, the net
      hepatic glucose output (NHGO; basal, 11.8 +/- 0.7 micromol x kg-1 x min-1) did
      not change initially (11.8 +/- 2.1 micromol x kg-1 x min-1, 30 min after the
      insulin increase), but eventually fell (P < 0.05 ) to 6.1 +/- 0.9 micromol x kg-1
      x min-1 (last 30 min). With a selective rise in portal insulin, NHGO dropped
      quickly (P < 0.05) from 10.0 +/- 0.9 to 5.6 +/- 0.6 micromol x kg-1 x min-1 (30
      min after the insulin increase) and eventually reached 3.1 +/- 1.1 micromol x kg
      1 x min-1 (last 30 min). When insulin levels were not increased (CONT group),
      NHGO dropped progressively from 10.1 +/- 0.6 to 8.3 +/- 0.6 micromol x kg-1 x min
      1 (last 30 min). Conclusions drawn from the net hepatic glucose balance data were
      confirmed by the tracer data. Net hepatic gluconeogenic substrate uptake (three
      carbon precursors) fell 2.0 micromol x kg-1 x min-1 in the PERI group, but rose
      1.2 micromol x kg-1 x min-1 in the PORT group and 1.2 micromol x kg-1 x min-1 in
      the CONT group. A selective 84 pmol/l rise in arterial insulin was thus
      associated with a fall in NHGO of approximately 50%, which took 1 h to manifest.
      Conversely, a selective 84 pmol/l rise in portal insulin was associated with a
      50% fall in NHGO, which occurred quickly (15 min). From the control data, it is
      evident that in either case approximately 30% of the fall in NHGO was due to a
      drift down in baseline and that 70% was due to the rise in insulin. In
      conclusion, an increment in portal insulin had a rapid inhibitory effect on NHGO,
      caused by the suppression of glycogenolysis, while an equal increment in arterial
      insulin produced an equally potent but slower effect that resulted from a small
      increase in hepatic sinusoidal insulin, from a suppression of gluconeogenic
      precursor uptake by the liver, and from a redirection of glycogenolytic carbon to
      lactate rather than glucose.

PMID- 8866567
TI  - The pituitary-gonadal axis and health in elderly men: a study of men born in
      1913.
AB  - The results of recent studies suggest that a relative hypogonadism in men is
      associated with several established risk factors for prevalent diseases.
      Therefore, we determined total and free testosterone, luteinizing hormone (LH),
      and sex-hormone binding globulin (SHBG) in a cohort of randomly selected men (n =
      659) at 67 years of age. These data were analyzed cross-sectionally in relation
      to blood glucose and serum insulin, which were measured while fasting and after
      an oral glucose tolerance test, in addition to plasma lipids and blood pressure.
      The data were also analyzed in relation to impaired glucose tolerance (IGT) and
      diabetes, which were discovered at examination or earlier diagnosis. Risk factors
      for the development of diabetes up to 80 years of age were analyzed with
      univariate and multivariate statistics. Total and free testosterone and SHBG
      concentrations correlated negatively with glucose and insulin values; total
      testosterone and SHBG, with triglycerides; and SHBG, with blood pressure (from P
      < 0.05 to P < 0.01). Men with IGT or newly diagnosed diabetes had higher BMI
      values (26.2 +/- 0.31 and 27.0 +/- 0.59 [mean +/- SE], respectively) and waist
      circumference (99.0 +/- 1.03 and 100.5 +/- 1.57) than nondiabetic men (BMI, 25.1
      +/- 0.14; waist circumference, 95.4 +/- 0.47; P < 0.05), indicating abdominal
      obesity. Such men and men with previously diagnosed diabetes had, in general,
      lower total and free testosterone and SHBG levels, while those for LH were not
      different. In multivariate analyses that included BMI, waist-to-hip ratio, total
      and free testosterone, and SHBG, the remaining independent predictors for the
      development of diabetes were low total testosterone (P = 0.015) and, on the
      borderline, low SHBG (P = 0.053). In relation to nondiabetic men, the risk ratio
      for mortality, myocardial infarction, and stroke increased gradually and
      significantly from 1.18 to 1.68, from 1.51 to 1.78, and from 1.72 to 2.46 in men
      with IGT, newly diagnosed diabetes, and previously known diabetes, respectively.
      It was concluded that low testosterone and SHBG concentrations in elderly men are
      associated with established risk factors for diabetes and in established
      diabetes. Moreover, low testosterone levels independently predict the risk of
      developing diabetes. In different degrees of expression, the diabetic state
      predicts strongly (and gradually mortality from) myocardial infarction and
      stroke. It has been suggested that a relative hypogonadism might be a primary
      event, because other studies have shown that testosterone deficiency is followed
      by insulin resistance, which is ameliorated by testosterone substitution. The
      data suggest that the relative hypogonadism involved might be of both central and
      peripheral origin.

PMID- 8866568
TI  - Imidazoline compounds stimulate insulin release by inhibition of K(ATP) channels
      and interaction with the exocytotic machinery.
AB  - A novel imidazoline compound, RX871024, was used to investigate the mechanisms by
      which imidazoline derivatives promote insulin secretion in rat pancreatic beta
      cells and HIT T15 cells. RX871024 stimulated insulin release from rat pancreatic
      beta-cells and HIT T15 cells in a glucose-dependent way. This effect was not
      related to alpha2-adrenergic, I1-, and I2-imidazoline receptors. RX871024
      promoted insulin release by at least two modes of action. One included an
      increase in cytoplasmic free Ca2+ concentration ([Ca2+]i), subsequent to blocking
      of ATP-dependent K+ channels, membrane depolarization, and activation of voltage
      dependent Ca2+ channels. The other, a more distal effect of imidazoline, affected
      the exocytotic machinery and was unrelated to changes in membrane potential and
      [Ca2+]i. The mechanism of RX871024-induced insulin release was dependent on
      protein kinases A and C. The sensitizing effect of a low dose of RX871024 on
      glucose-induced insulin secretion suggests that imidazoline compounds of this
      kind may constitute the basis for development of a new class of oral hypoglycemic
      agents.

PMID- 8866570
TI  - Low mitochondrial glycerol phosphate dehydrogenase and pyruvate carboxylase in
      pancreatic islets of Zucker diabetic fatty rats.
AB  - The enzyme activities of mitochondrial glycerol phosphate dehydrogenase (mGPD)
      (EC 1.1.99.5) and pyruvate carboxylase (PC) (EC 6.4.1.1) have been reported to be
      low in the pancreatic islet of several rodent models of NIDDM. The present study
      was undertaken to discern whether mGPD is abnormal in the Zucker diabetic fatty
      (ZDF) rat (ZDF/Gmi-fa/fa), an animal model of NIDDM in which insulin secretion is
      unable to counteract the insulin resistance associated with the obesity that
      characterizes this model. Experiments were performed in prediabetic 6-week-old
      ZDF rats in comparison with 12-week-old overtly hyperglycemic animals and, as
      controls, Zucker lean (ZL) rats (ZDF/Gmi-+/fa or -+/+) and Wistar rats (+/+) of
      the same ages. The enzyme activity of mGPD was 32 and 18% of normal in islets of
      6- and 12-week-old ZDF rats, respectively (P < 0.001 by analysis of variance).
      The activity of PC, which like mGPD is relatively abundant in the pancreatic
      islet, was 17 and 10% of normal in the islets of 6- and 12-week-old ZDF rats,
      respectively (P < 0.001). The activity of mGPD was normal in islets from ZL rats.
      However, PC activity was slightly lower in islets of 6- (51% of normal, P =
      0.007) and 12-week-old (67% of normal, P = 0.01) ZL rats. The amounts of mGPD
      protein, as judged from Western analysis, and of PC protein, as judged from
      probing transblots with streptavidin that binds to biotin-containing enzymes,
      roughly correlated with the enzyme activities. This indicates that the decreased
      enzyme activities are caused by the decreased net synthesis of these enzymes
      rather than by the decreased activity of a normal amount of enzyme. The enzyme
      activity of succinate dehydrogenase, a control for mGPD, was normal in the ZL and
      ZDF rats. An incidental finding of the current study was the discovery of beta
      methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase in the islet. Levels
      of these enzymes were also normal. Although reductions in mGPD and PC may
      contribute to the abnormal insulin secretion present in overt diabetes, they are
      modest compared with the severe reductions seen in inherited inborn errors of
      metabolism. Because of this and because more than a single enzyme is affected and
      the enzymes in the islet are diminished in more than one rodent model of NIDDM,
      these reductions are unlikely to represent the primary genetic defect in the ZDF
      rat. Since ZDF rats are euglycemic at 6 weeks of age and ZL animals are
      euglycemic throughout life and since these animals demonstrate low enzyme
      activities, this evidence suggests that it is not hyperglycemia but rather some
      other component of the diabetic syndrome that is responsible for the reductions
      in these enzymes.

PMID- 8866569
TI  - Epidermal growth factor induces glucose storage in transgenic 3T3-L1 adipocytes
      overexpressing epidermal growth factor receptors.
AB  - 3T3-L1 adipocytes represent an established physiological model for studying
      glucose uptake and storage. Overexpression of epidermal growth factor (EGF)
      receptors in these cells (200,000-250,000 receptors per cell) confers EGF
      inducible GLUT4-mediated glucose uptake (17). We now report that EGF receptor
      (EGFR)-mediated signals can induce incorporation of glucose into glycogen and
      lipids in these cells. Incorporation into lipids was stimulated to similar levels
      by insulin or EGF in adipocytes expressing full-length (wild type) EGFR (2.05 +/-
      0.26-fold for insulin vs. 2.28 +/- 0.15-fold for EGF). EGF induced incorporation
      into glycogen at roughly 60% of the level of insulin (4.53 +/- 0.57-fold for
      insulin vs. 2.76 +/- 0.25-fold for EGF); this corresponded with similarly lower
      levels of glycogen synthase activation by EGF relative to insulin stimulation.
      EGFR kinase activity was required for induced storage because a kinase-inactive
      (M721) EGFR failed to stimulate glucose incorporation into glycogen or lipids.
      EGFRs that lack all or part of the unique EGFR COOH-terminal tail induced glucose
      incorporation at levels similar to that stimulated by full-length (wild type)
      EGFR. Thus, domains in the COOH-terminal tail of the EGFR, which are necessary
      for stimulating glucose transport, are not required for signaling EGF-induced
      glucose storage. EGF-induced glucose storage did not require de novo protein
      synthesis, suggesting that EGFR signaling uses existing pathways in the
      adipocytes. These data demonstrate that signaling pathways for EGFR-mediated
      glucose storage and GLUT4-mediated glucose transport diverge at the receptor
      level. Thus, EGF-induced glucose storage can be achieved in the absence of
      induced GLUT4-mediated glucose transport.

PMID- 8866571
TI  - Nicotinamide's effects on glucose metabolism in subjects at risk for IDDM.
AB  - Nicotinamide is being used in trials to prevent or delay the development of
      clinical IDDM. A related compound, niacin, has been shown to cause insulin
      resistance in normal subjects, resulting in increased insulin secretion. This
      study was designed to answer the question: Does the short-term administration of
      nicotinamide cause insulin resistance in subjects who have a high risk of
      developing IDDM? Eight islet cell antibody-positive (ICA+) relatives of IDDM
      patients were given nicotinamide at a dose of 2 g/day for 2 weeks. Measurements
      of first-phase insulin release, insulin sensitivity, glucose effectiveness, and
      the constant for glucose disappearance (Kg) were measured at baseline, at the end
      of 2 weeks of therapy, and after subjects had been off therapy for at least 2
      weeks. Nicotinamide administration caused a 23.6% decrease in insulin sensitivity
      (P = 0.02). This decrease was associated with a fall in Kg despite increased
      insulin secretion. Our data suggest that the use of nicotinamide in subjects who
      are at risk of developing IDDM may be complicated by the drug's effects on
      insulin sensitivity. By inducing insulin resistance, a therapeutic effect of
      nicotinamide on the diabetes disease process may be missed, and the
      interpretation of insulin secretion measurements that are obtained during the
      intervention trials using nicotinamide may be complicated by the changes in
      insulin secretion that are caused by the increased insulin resistance. Therefore,
      we strongly support the recommendation that at least one subgroup of subjects
      enrolled in clinical trials to prevent IDDM have regular measurements of both
      insulin sensitivity and insulin secretion performed. This subgroup should be
      randomly assigned and large enough for statistical analysis to interpret properly
      the changes in insulin secretion that may occur.

PMID- 8866572
TI  - Leptin: a significant indicator of total body fat but not of visceral fat and
      insulin insensitivity in African-American women.
AB  - The recently cloned adipose tissue hormone leptin has been proposed to be
      involved in the neuroendocrine regulation of adiposity and its metabolic
      sequelae. Visceral fat is known to predict reduced insulin sensitivity and
      associated adverse metabolic profiles. In this study, we report the first
      evaluation of the relationships between leptin levels and total body fat,
      visceral fat, and insulin sensitivity in a cohort of premenopausal African
      American women. Thirty-four subjects were analyzed for total fat mass and
      visceral fat by dual-energy X-ray absorptiometry and computerized axial
      tomography, respectively. Insulin sensitivity (SI) was assessed using Bergman's
      minimal model. Results showed that fasting leptin levels strongly correlated with
      total body fat mass (r = 0.797, P < 0.001). Correlations of leptin with visceral
      fat (r = 0.54, P < 0.001) and SI (r = -0.419, P = 0.02) were dependent on total
      body fat. In conclusion, leptin levels reflect total body fat mass, and although
      visceral fat is known to predict reduced insulin sensitivity independently,
      leptin did not. Our data thus suggest that diverse mechanisms are responsible for
      the regulation of total body versus visceral fat distribution, with its metabolic
      and health risks.

PMID- 8866573
TI  - Evidence for leptin binding to proteins in serum of rodents and humans:
      modulation with obesity.
AB  - Many hormones circulate bound to serum proteins that modulate ligand bioactivity
      and bioavailability. To understand the biology of leptin action, we investigated
      the presence of leptin binding proteins in serum. 125I-labeled leptin binds
      competitively to at least three serum macromolecules with molecular masses of
      approximately 85, approximately 176, and approximately 240 kDa in rodents and
      approximately 176 and approximately 240 kDa in humans. The ability to bind
      appears to involve sulfhydryl/disulfide interactions because it is inhibited
      under reducing conditions. When serum is added to recombinant 125I-leptin, there
      is a shift in sedimentation of 125I-leptin as analyzed by sucrose gradient
      centrifugation from approximately S1.9 to approximately S4.3. This shift is
      markedly attenuated in serum from obese mice (ob/ob, db/db, brown-fat ablated,
      gold-thioglucose treated, high-fat fed) compared with that from nonobese
      controls. The size distribution of endogenous serum leptin as determined by
      radioimmunoassay (RIA) after sucrose gradient centrifugation is also consistent
      with saturation of binding in hyperleptinemic obesity. In humans, free leptin
      increases with BMI. Thus, in lean rodents and humans a large proportion of leptin
      circulates bound to several serum proteins. Free leptin is increased in serum of
      obese subjects, which may alter leptin bioactivity, transport, and/or clearance.

PMID- 8866574
TI  - Lilly lecture 1995. Glucose transport: pivotal step in insulin action.
AB  - The effect of insulin to acutely stimulate glucose uptake into muscle and adipose
      tissue is essential for normal glucose homeostasis. The GLUT4 glucose transporter
      is a major mediator of this action, and insulin recruits GLUT4 from an
      intracellular pool to the plasma membrane. An important pathologic feature of
      obesity, NIDDM, and to a lesser extent IDDM is resistance to insulin-stimulated
      glucose uptake. Investigations of the mechanisms have revealed tissue-specific
      regulation of GLUT4 with decreased gene expression in adipose cells but not in
      skeletal muscle. This has led to the hypothesis that alterations in the
      trafficking of the GLUT4 vesicle or in the exposure or activation of the GLUT4
      transporter may cause insulin resistance in skeletal muscle in obesity and
      diabetes. Exercise training increases GLUT4 expression in muscle in association
      with enhanced glucose tolerance in vivo. Transgenic mice have been created to
      investigate other approaches to improve insulin action on glucose transport.
      Overexpression of GLUT4 in adipocytes of transgenic mice increases the proportion
      of GLUT4 on the plasma membrane and enhances insulin sensitivity in vivo.
      Altering insulin signaling by overexpressing p21ras in adipocytes of transgenic
      mice results in increased GLUT4 on the plasma membrane in the absence of insulin
      and increases insulin sensitivity in vitro and in vivo. Thus, glucose transport
      is a pivotal step in whole-body insulin action. Strategies to increase the number
      of GLUT4 transporters that are functionally inserted in the plasma membrane in
      muscle and adipocytes may lead to new therapies to treat or prevent NIDDM.

PMID- 8866575
TI  - Bronchial biopsies and airway inflammation.

PMID- 8866576
TI  - Lower respiratory tract infections in the community: towards a more rational
      approach.

PMID- 8866577
TI  - Initial antibiotic therapy for lower respiratory tract infection in the
      community: a European survey.
AB  - A survey of first-line antibiotic prescription in community-acquired lower
      respiratory tract infection (LRTI) by general practitioners (GP) was carried out
      simultaneously, using the same methodology in France, Germany, Italy, Spain and
      the UK. Data were obtained from 2,056 patients and 605 GPs. There was no
      antibiotic prescription in 17% of all LRTIs and 13% of community-acquired
      pneumonia (CAP) in the five countries taken together; and in 32% of all LRTIs and
      in 23% of CAP in Germany. Of patients with acute bronchitis, exacerbation of
      chronic bronchitis and viral lower respiratory tract infection, 87, 92 and 71%
      received antibiotics, respectively. The most frequent prescriptions were
      penicillins in France and the UK, third-generation cephalosporin in Italy,
      tetracycline in Germany and macrolide in Spain. The daily dosage of
      aminopenicillin prescribed was: 41% <1.5 g; 49% > or = 1.5 g and <3 g; and 10% >
      or = 3 g. In Italy, 53% of all antibiotics were injected in all LRTIs, and 71% in
      CAP; in contrast, antibiotic injection was lower than 2% both in the UK and
      Germany, with an average of 14% in the five countries combined. We conclude that
      there are variations in antibiotic prescription by GPs in Western Europe;
      differences are likely to be multifactorial, but could, in part, be explained by
      differences in health systems and sources of information available to GPs.

PMID- 8866579
TI  - Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa.
AB  - Sputum isolation of Pseudomonas aeruginosa (PA) is associated with extensive
      disease in bronchiectasis. It is not known, however, whether infection with P.
      aeruginosa is the result or the cause of severe disease. We compared spirometry
      in patients with bronchiectasis before and after infection with P. aeruginosa,
      with that of patients infected by other organisms. All patients (n=12) with
      chronic colonization by P. aeruginosa (PA group) were studied. These were
      compared with other patients with bronchiectasis with no isolations of P.
      aeruginosa (n=37, non-PA group). In the PA group, forced expiratory volume in one
      second (FEV1) and forced vital capacity (FVC) were lower than in the non-PA
      group. The PA group, however, also had lower values at the time of initial
      colonization with P. aeruginosa than the current values for the non-PA group.
      Change in FEV1 and FVC over time was faster in the PA group than in the non-PA
      group. Reduction of FEV1 and FVC over time in the PA group prior to P. aeruginosa
      colonization was intermediate, not being statistically different from either
      value above. Our results confirm the association of chronic P. aeruginosa
      colonization with poor lung function, but conclude that patients with
      bronchiectasis who become colonized by P. aeruginosa have poorer lung function
      when first colonized than those colonized by other organisms. Decline in lung
      function is faster in those chronically colonized by P. aeruginosa than in those
      colonized by other organisms. It is not clear whether chronic P. aeruginosa
      colonization causes an accelerated decline in lung function or whether it is
      simply a marker of those whose lung function is already declining rapidly.

PMID- 8866578
TI  - Use of investigations in lower respiratory tract infection in the community: a
      European survey.
AB  - A questionnaire survey was performed on the use of investigations and their
      impact on treatment of adult lower respiratory tract infection in the community.
      Data on the management of 2,056 such infections were obtained simultaneously from
      general practitioners in France, Germany, Italy, Spain and the UK. Diagnostic
      tests were only performed in 29% of cases. Chest radiographs were performed most
      frequently (22%), followed by peripheral blood white cell count (15%) and
      microbiological examination of sputum (7%), with major differences being found in
      the frequency of these tests both by clinical diagnosis and country. A change in
      initial antibiotic therapy was made in 12% of cases, with use of investigation
      being significantly linked to such changes. Second- and third-line antibiotics
      were significantly different to first-line therapy, with macrolides the most
      frequently prescribed second-line and quinolones the most frequently prescribed
      third-line antibiotics.

PMID- 8866580
TI  - Long-term home care programmes may reduce hospital admissions in COPD with
      chronic hypercapnia.
AB  - Long-term oxygen therapy (LTOT) has been shown to improve survival in chronic
      obstructive pulmonary disease (COPD) patients. The clinical effectiveness of long
      term home mechanical ventilation (HMV) is still discussed, nevertheless both LTOT
      and HMV are often included in the home care programmes of these patients. To
      evaluate the effectiveness of home care programmes including either HMV or LTOT,
      34 COPD patients were studied. They were admitted to either HMV (Group A: 12
      males and 5 females, aged 62 +/- 5 yrs), or LTOT (Group B: 9 males and 8 females,
      aged 62 +/- 8 yrs). They were compared to a historical group (Group C: 19 males
      and 10 females, aged 67 +/- 16 yrs) performing only their usual standard LTOT
      during the same period. Spirometry, maximal inspiratory pressure and arterial
      blood gas values were assessed at baseline and at 6, 12 and 18 months of follow
      up. Mortality rate and number of hospital and intensive care unit (ICU)
      admissions and days of hospitalization were also assessed. Four out of 17 (23%)
      patients in Group A, 3 out of 17 (18%) in Group B, and 5 out of 29 (17%) in Group
      C died within 18 months. Of the lung function tests, only maximal inspiratory
      pressure in Group A showed a significant increase in the 18th month (50 +/- 4 to
      56 +/- 7 cmH2O; p<0.01). In comparison to 18 months prior to the study, hospital
      admissions (from 2.2 +/- 0.6 to 1.3 +/- 1.1 and from 2.0 +/- 0.7 to 1.0 +/- 0.9
      for Group A and B, respectively; p<0.005 for both), and days of hospitalization
      (from 60 +/- 34 to 34 +/- 40 and from 55 +/- 23 to 18 +/- 20 days in Group A and
      B, respectively; p<0.005 for both) significantly decreased only in the two groups
      submitted to the home care programme. We conclude that home care programmes may
      be effective in the long-term treatment of chronically hypercapnic chronic
      obstructive pulmonary disease patients in reducing hospital admissions.

PMID- 8866581
TI  - Upper airway size and collapsibility in snorers: evaluation with digital
      fluoroscopy.
AB  - This study addressed the question of whether there are any differences in the
      size and collapsibility of the upper airway measured by digital fluoroscopy,
      between snorers and controls whilst they were awake and breathing normally; and
      whether there are any correlations between these measurements and other clinical
      data. The dynamic changes of the upper airway size were evaluated using digital
      fluoroscopy in 33 patients and 16 normal controls. The measurements were compared
      with findings in an overnight sleep study, including a static-charge-sensitive
      bed (SCSB) and oximeter recordings. The minimum anteroposterior dimension at the
      velopharyngeal level was smaller in patients with partial upper airway
      obstruction than in controls (p<0.005); patients with complete obstruction did
      not differ from the controls. The velopharyngeal airways were also more
      collapsible in patients with severe partial obstruction (p<0.01) than in
      controls. At the oropharyngeal and hypopharyngeal levels, the dimensions and the
      collapsibilities were similar in patients and controls. The velopharyngeal
      collapsibility correlated with body mass index (p<O.001), whereas the airway size
      did not. The velopharyngeal collapsibility was more pronounced in patients with
      frequent episodes of arterial oxyhaemoglobin desaturation during sleep.
      Velopharyngeal collapsibility associated with high body mass index was the
      important determinant of nocturnal breathing disturbances. Digital fluoroscopy
      displays the dynamic changes of the upper airways throughout the respiratory
      cycle.

PMID- 8866582
TI  - Recycling of hard-core smokers with nicotine nasal spray.
AB  - The primary aim of this smoking cessation study was to evaluate the effect of
      long-term treatment with nicotine nasal spray in a group of hard-core smokers. A
      further aim was to compare the effect of ad libitum with fixed dosage of nasal
      nicotine spray. Eighty nine smokers, failures from two earlier studies with
      nicotine patches, were enrolled in an open smoking cessation study with nicotine
      nasal sprays, to be used ad libitum (n=45) or on a fixed schedule of 1 mg x h-1
      during the day (n= 44). Carbon monoxide-verified continuous abstinence from
      smoking beyond Week 2, was 39% at 3 weeks, 12% at 3 months, 10% at 6 months and
      6% after 1 yr, with no significant difference in success rate between ad libitum
      and fixed dosing. Mean daily nicotine dose was 15-16 mg during the first 3 months
      (range 2-65 mg). Tolerance to local irritating side-effects of nicotine developed
      during the first weeks of use. Although short-term outcome was promising, the
      long-term success rate in this group of hardcore smokers was low. Other recycling
      set-ups are warranted, which might include more aggressive nicotine dosing.

PMID- 8866583
TI  - Female gender as a determinant of cough threshold to inhaled capsaicin.
AB  - Chronic, nonproductive cough and cough associated with the use of angiotensin
      converting enzyme inhibitors, are more frequently observed in females as compared
      to males. To examine the influence of sex, age, height, weight and pulmonary
      function on airway cough sensitivity, cough threshold to inhaled capsaicin, an
      index of the airway cough sensitivity, was measured in 160 nonsmoking, nonatopic
      healthy subjects. Forty young males (aged 24 +/- 2 yrs) 40 young females (aged 22
      +/- 2 yrs) 40 middle-aged males (aged 48 +/- 5 yrs) and 40 middle-aged females
      (aged 50 +/- 7 yrs) were studied. The cough threshold was defined as the lowest
      concentration of inhaled capsaicin causing five or more coughs. The cough
      threshold was 3-5 fold lower in females than in males both in young (p<0.001) and
      middle-aged (p<0.005) subjects. Cough threshold was weakly but significantly
      correlated to height, weight, forced vital capacity (FVC) and forced expiratory
      volume in one second (FEV1) when all subjects were considered together but not
      when each group was considered separately. Multiple regression analysis revealed
      that sex difference was the significant predictive factor for the cough threshold
      in either age group. These results confirm that cough sensitivity is heightened
      in females and suggest that influence of height and pulmonary function on the
      cough threshold may have resulted from sex difference.

PMID- 8866584
TI  - Effect of cessation of short-term therapy with ipratropium bromide on lung
      function and airway responsiveness.
AB  - Regular exposure to antimuscarinic drugs would be expected to upregulate airway
      muscarinic receptors and could cause a transient increase in airways obstruction
      if treatment was stopped or omitted. We have examined peak expiratory flow rate
      (PEFR) during treatment and forced expiratory flow in one second (FEV1) and
      airway responsiveness to three constrictor agonists (as the provocative dose of
      agonist causing a 20% fall in FEV1, (PD20)) following cessation of regular
      inhaled ipratropium bromide, in 13 subjects with mild stable asthma. Subjects
      inhaled placebo and ipratropium bromide, 80 microg q.i.d. for 14 days in a cross
      over fashion with a 1 week run-in/wash-out period before and after each treatment
      period. Subjects recorded symptom scores and PEFR throughout the study, and FEV1
      and PD20 to histamine, methacholine and metabisulphite were measured before and
      after cessation of treatment. When compared to baseline, FEV1 was lower after
      cessation of ipratropium than after placebo, with a significant difference 30 h
      after the last dose (difference 190 mL; 95% confidence interval (95% CI) 310-70
      mL; p<0.02). FEV1 measured 6-10 days later, did not differ significantly. PEFR
      was significantly lower after cessation of ipratropium than after placebo on Day
      15 (19-37 h after the last dose) (mean difference 4.6%; 95% CI 1.6-7.5%; p<0.01)
      but not on Day 16. There were no significant changes in PD20 histamine,
      methacholine and metabisulphite, symptom scores or rescue bronchodilator use
      after cessation of treatment. Thus, transient bronchoconstriction was found
      around 30 h after cessation of regular therapy with inhaled ipratropium for 2
      weeks. The mechanism is unclear, as no evidence of muscarinic receptor
      upregulation was found. Although the changes were small and unlikely to be
      important for most patients, the results of this study indicate that the timing
      of lung function measurements relative to the last dose of ipratropium is
      important when interpreting the course of lung function in long-term studies.

PMID- 8866585
TI  - Cholinergic control of rabbit tracheal transepithelial potential difference in
      vivo.
AB  - The aim of the present study was to investigate the role of the autonomic nervous
      system in the regulation of airway epithelial ion transport in vivo. Rabbits were
      anaesthetized and mechanically-ventilated through a cannula inserted above the
      carina. The upper tracheal mucosa was exposed, and the electrical potential
      difference (PD) between the mucosal surface and the submucosal space was
      continuously measured by a high-impedance voltmeter under open-circuit
      conditions. Perfusion of the mucosa with atropine caused a rapid decline in PD
      from -20.1+/-2.0 to -15.2+/-0.9 mV (p<0.01), whereas phentolamine, propranolol,
      or the tachykinin antagonist, FK224, had no effect. Cutting both cervical vagus
      nerves decreased PD to the same degree as did atropine. Exogenously applied
      acetylcholine increased PD in a dose-dependent manner. Topical application of
      ipratropium bromide reduced the baseline value PD in a dose-dependent manner. The
      maximal decrease in PD was 43 +/- 0.3 mV (p<0.01), and the dose required to
      produce a half-maximal effect was 34 microg. Perfusion with either amiloride, a
      Na channel blocker, and diphenylamine-2-carboxylate, a Cl channel blocker,
      decreased the baseline PD, and the subsequent application of ipratropium bromide
      further decreased the PD in each case. We conclude that a cholinergic neural
      component may play a role in the generation of tracheal potential difference in
      vivo, probably involving stimulation by endogenously released acetylcholine of
      both Cl secretion and Na absorption across the airway epithelium.

PMID- 8866586
TI  - Adaptation of pulmonary receptors in the spontaneously breathing anaesthetized
      rat.
AB  - It has been suggested that species with high breathing frequencies have pulmonary
      stretch receptors which adapt more rapidly than species with low breathing
      frequencies. This has proved not to be so. Our hypothesis is that this theory is
      in fact correct if modified so that overall rate of adaptation of afferent vagal
      activity, i.e. the sum of stretch and rapidly adapting receptors, is considered.
      A rapidly breathing species, such as the rat, would thus have a greater
      proportion of rapidly adapting receptors, than a more slowly breathing species.
      To test this hypothesis, we measured the proportion of rapidly adapting pulmonary
      mechanoreceptors in spontaneously breathing rats for comparison with existing
      results from more slowly breathing species. We found there to be one rapidly
      adapting receptor for every three slowly adapting receptors present. This
      measurement has not previously been made in spontaneously breathing rats. The
      ratio of rapidly to slowly adapting pulmonary receptors in the species sequence
      cat-rabbit-rat is the same as the ratio of their breathing frequencies (3:4:10).
      We propose that the difference in proportion of slowly to rapidly adapting
      pulmonary receptors in different species may be related to their eupnoeic
      breathing frequency.

PMID- 8866587
TI  - Tumour necrosis factor receptor gene expression and shedding in human whole lung
      tissue and pulmonary epithelium.
AB  - This study aimed to investigate the expression of tumour necrosis factor receptor
      (TNF-R) at the gene and surface level, and its shedding in human lung tissue and
      a pulmonary epithelial cell line, A549. Levels of gene expression of TNF-R were
      evaluated by Northern blot analysis. Human lung tissue expressed both type I and
      type II TNF-R gene, while A549 cells expressed only type I TNF-R gene. Phorbol
      ester upregulated and TNF-alpha down-regulated the TNF-R gene expression in A549
      cells. Consistent with these modulations of TNF-R gene expression, 125I-TNF
      binding capacities were increased with phorbol ester stimulation and decreased
      with TNF stimulation after 24 h in A549 cells. The shedding of TNF-R from A549
      cells was investigated using enzyme-linked immunosorbent assay (ELISA) for
      soluble type I TNF-R. Not only lung tissues but also A549 cells spontaneously
      released soluble type I TNF-R into the culture medium. Both phorbol ester and TNF
      stimulation accelerated the shedding of soluble TNF-R from A549 cells. These
      results suggest that type I TNF-R gene expression and shedding of soluble TNF-R
      are differentially regulated in A549 cells. We conclude that tumour necrosis
      factor receptor surface expression is regulated, at least in part, at the gene
      expression level and shedding of soluble tumour necrosis factor receptor is
      modulated by inflammatory mediators, such as tumour necrosis factor in A549
      cells.

PMID- 8866588
TI  - Serum type I and type III procollagen peptide levels in sarcoidosis.
AB  - Type I and type III are the most abundant collagens in the lung. The aim of our
      study was to compare type I and III procollagen peptides in sera of sarcoid
      patients. Sixty eight patients with sarcoidosis were studied (19 with newly
      recognized disease, 7 with relapsing disease, 15 with chronic disease, and 27 in
      stable remission). Thirty healthy volunteers served as controls. The levels of
      procollagen I and III peptides were determined by radioimmunoassay. Angiotensin
      converting enzyme (ACE) level was evaluated by means of a colorimetric assay. In
      patients with newly recognized sarcoidosis, both serum procollagen I and III
      peptide levels were increased with respect to controls (p=0.0014 and p<0.00001,
      respectively). There was a poor correlation between levels of procollagen I and
      III (r=0.26), whereas there was a closer correlation between procollagen III and
      ACE (r=0.69). Procollagen I peptide level did not identify patients in
      roentgenological stage III. In conclusion, in patients with newly recognized
      sarcoidosis there is a significant increase in the serum level of procollagen I
      peptide. However, procollagen I peptide is not a marker of sarcoid patients with
      fibrosis, ie. stage III disease. Its clinical usefulness seems to be weaker than
      that of procollagen III peptide.

PMID- 8866589
TI  - Pleural fluid interferon-gamma and tumour necrosis factor-alpha in tuberculous
      and rheumatoid pleurisy.
AB  - Tuberculous and rheumatoid pleural effusions show features suggesting a strong
      local cellular immune response. Pleural fluid (Pf) from patients with
      tuberculosis, rheumatoid arthritis (RA) and other diseases were compared with
      respect to interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF
      alpha). Immunoassays were used to determine Pf-IFN-gamma and Pf-TNF-alpha in 102
      patients, including 11 with RA, 31 with verified tuberculosis, 23 with suspected
      tuberculosis, 11 with pneumonia, 14 with lung cancer and 12 with congestive heart
      failure. Measurable Pf-IFN-gamma occurred exclusively in patients with verified
      (median 1.8 ng x mL-1; 95% confidence interval (95% CI) 0.63-4.0 ng x mL-1) or
      suspected (0.37 ng x mL-1; 95%CI 0-0.7 ng x mL-1) tuberculosis. The highest
      median Pf-IFN-gamma was observed in those patients who showed a positive pleural
      fluid culture for Mycobacterium tuberculosis. In pleural effusions due to other
      diseases, including RA, IFN-gamma was undetectable. The highest Pf-TNF-alpha
      occurred in verified tuberculosis (median 198 ng x L-1; 95% CI 169-222 ng x L-1)
      and RA (210 ng x L-1; 95% CI 147-231 ng x L-1). Pleural fluid interferon-gamma is
      a highly useful marker for diagnosing tuberculous pleurisy. Although tuberculous
      and rheumatoid pleural effusions share several biochemical features, they are
      strikingly different with respect to interferon-gamma.

PMID- 8866590
TI  - Intrapleural urokinase in the treatment of complicated parapneumonic pleural
      effusions and empyema.
AB  - Intrapleural urokinase has not been evaluated systemically in terms of efficacy,
      safety, and cost of treatment in a large series of patients with complicated
      (parapneumonic) pleural effusions (CPE) and pleural empyemas (PE). Furthermore,
      the optimal dose and duration of treatment is not known. Twenty consecutive
      patients with multiloculated parapneumonic effusions (13 with CPE and 7 with PE),
      in whom a single chest tube failed to drain the fluid, were studied
      prospectively. The age of the patients ranged 15-92 yrs (median 51 yrs).
      Urokinase was administered intrapleurally, in a low single daily dose of 50,000 U
      in 100 mL normal saline via the chest tube. Previous intrapleural instillation of
      100 mL normal saline failed to promote drainage in all patients. Urokinase
      enhanced drainage in all patients. Clinical and radiological improvement was
      noted in all but one patient. The mean (SD) volume of fluid significantly
      increased in the first 24 h post-urokinase (p<0.001). The number of urokinase
      instillations ranged 3-7 (median 5). Radiological evaluation showed excellent
      improvement in 13 of the 20 (65%) patients. Urokinase was well-tolerated in all
      patients. The clinical course of patients was uneventful at a mean follow-up of
      15 months (range 6-30 months) later. Mean total cost of treatment was $530 +/-
      34.6. Our results show that intrapleural instillation of small doses of urokinase
      is a cost-effective and safe mode of treatment of complicated pleural effusions
      and pleural empyema and could be the fibrinolytic of choice.

PMID- 8866591
TI  - Thoracoscopic sympathicolysis for essential hyperhidrosis: effects on pulmonary
      function.
AB  - Bilateral interruption of the upper dorsal sympathetic chain at the D2 and D3
      level represents the only permanent cure for essential hyperhidrosis. Following
      surgical sympathectomy, significant and symptomatic changes in pulmonary function
      have been observed. Since functional effects of the surgical intervention cannot
      be excluded, we wondered whether such alterations also occurred after
      thoracoscopic sympathicolysis; these should then be attributable to the surgical
      denervation itself. Pulmonary function tests (PFTs), including spirometry and
      body plethysmographic measurement of lung volumes and airway resistance and
      conductance, were compared before and 6 weeks after thoracoscopic sympathicolysis
      in 47 patients. In order to virtually exclude any effects of thoracoscopy on the
      test results PFTs were repeated 6 months after thoracoscopic sympathicolysis in
      35 patients. Essential hyperhidrosis was completely relieved in all patients,
      thereby confirming the interruption of the D2-D3 sympathetic chain. None of the
      patients developed respiratory symptoms after thoracoscopic sympathicolysis.
      Forced expiratory volume in one second (FEV1) (-3%), forced expiratory flow after
      exhaling 75% of vital capacity (FEF75) (-8%) and total lung capacity (TLC) (-3%)
      were slightly but significantly reduced at six weeks after thoracoscopic
      sympathicolysis; whereas airway resistance (Raw) had increased (+12%). After
      correction for the small decrease in lung volume (FEV1/forced vital capacity
      (FVC), specific airway resistance (sRaw), specific airway conductance
      (sGaw))significant changes in "volume-dependent" PFT parameters were no longer
      observed. Smoking status had no influence on the reduction in FEF75. At 6 months
      after thoracoscopic sympathicolysis, TLC had returned to preoperative values,
      whereas FEF75 remained decreased (-8.6%). The decrease in airway calibre was
      confirmed by small but significant changes in FEV1/FVC (-2%) and Raw (+29%). We
      conclude that thoracoscopic sympathicolysis in patients with essential
      hyperhidrosis causes only minimal and subclinical changes in pulmonary function
      secondary to a temporary small decrease in lung volume, which in turn is probably
      inherent to the thoracoscopic procedure. D2-D3 sympathicolysis, in itself, is
      responsible only for a small and permanent decrease in forced expiratory flow,
      which suggests that, at least in essential hyperhidrosis patients, airway
      bronchomotor tone is influenced by sympathetic innervation.

PMID- 8866592
TI  - Bronchial brush biopsies for studies of epithelial inflammation in stable asthma
      and nonobstructive chronic bronchitis.
AB  - Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary
      method to bronchial forceps biopsy for the study of bronchial epithelial cells.
      We wanted to determine whether epithelial inflammatory cells in bronchial brush
      biopsies can reflect mucosal inflammation assessed indirectly by levels of
      cellular activation markers in bronchial lavage fluid. We studied 15 healthy
      controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics
      without steroids, and 10 smokers with nonobstructive chronic bronchitis.
      Differential counts of epithelial and inflammatory cells were made from the BBB
      material. Bronchial lavage levels of eosinophil cationic protein (ECP),
      myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were
      measured as indirect markers for inflammatory cell activation. We found an
      increased percentage of eosinophil granulocytes in the BBB from the steroid
      untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%,
      0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic
      patients, the percentage of eosinophils correlated with ECP in bronchial lavage
      fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of
      eosinophilic activation. A negative correlation was found for the percentage of
      eosinophils in BBB with levels of provocative concentration of methacholine
      causing a 20% fall in forced expiratory volume in one second (PC20) for the
      asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy
      method appears to give information on the changes present in superficial
      bronchial epithelium in inflammatory airways disease. These changes appear to
      relate to the degree of inflammatory activity and disease severity in asthma.

PMID- 8866593
TI  - Effects of theophylline on inflammatory cells and cytokines in asthmatic
      subjects: a placebo-controlled parallel group study.
AB  - The anti-inflammatory effects of oral theophylline on cells in bronchial biopsies
      of symptomatic atopic asthmatic subjects were investigated. Following a 2 week
      run-in period, asthmatic subjects were randomly assigned to either placebo (n=11)
      or theophylline (n=15). Bronchial biopsies were taken at fibre-optic bronchoscopy
      at the beginning and end of a 6 week period, during which subjects took placebo
      or theophylline medication at a dose intended to produce therapeutic
      concentrations. Nine of the placebo subjects and 12 of the theophylline subjects
      completed the study. Improvement in asthma control was seen in the theophylline
      treated group. The mean (SD) theophylline blood level at the end of the study was
      10.9 (6.0) microg x mL-1. A significant decrease in interleukin (IL)4 expression
      from 1.38 to 1.04 cells x mm-2 (<0.05) and a trend to a reduction in IL-5 from
      1.29 to 0.48 cells x mm-2 (NS) were seen in biopsies from the theophylline
      treated group compared with placebo, although there was no change in mast cell
      numbers (judged by tryptase expression). A decrease in epithelial CD8+ cells from
      2.60 to 0.53 cells x mm-1 of surface (<0.05) was noted. This study shows an anti
      inflammatory effect of theophylline in asthmatic bronchi, both in cell numbers
      and in the expression of IL-4, believed to be an important cytokine in the
      pathophysiology of asthmatic inflammation. We speculate that theophylline induces
      downregulation in vivo of cytokine production, accounting for the known
      inhibitory effect of theophylline on the late asthmatic reaction.

PMID- 8866594
TI  - A dose-response study with formoterol Turbuhaler as maintenance therapy in
      asthmatic patients.
AB  - The aim of this randomized, double-blind, parallel group study was to determine
      the lowest effective dose of 6, 12 and 24 microg formoterol fumarate dihydrate
      Turbuhaler b.i.d. compared with placebo. The 4 week treatment was preceded by a 1
      week run-in period. Morning peak expiratory flow (PEF) before intake of the study
      drug was the primary variable. Patients recorded PEF, prior to and 15 min after
      intake of the study drug (immediate response), asthma symptoms, and use of rescue
      medication morning and evening. Of 221 patients (71 females and 150 males), 194
      were included in the efficacy per protocol (PP) analysis; mean age 47 yrs, mean
      forced expiratory volume in one second (FEV1) 2.01 L (58% of predicted), mean
      FEV1 reversibility 27% at entry. Ninety percent used inhaled steroids. Compared
      with placebo, 6 microg formoterol b.i.d was found to be the lowest effective dose
      in the morning (p=0.008) and evening p=0.0041) PEF. The mean increases in PEF
      were 22 and 23 L x min-1 respectively, compared with placebo. After 6 microg
      formoterol, the mean immediate increase in morning PEF was 42 L x min-1 compared
      to an increase of only 9 L x min-1 after placebo (<0.0001). All doses produced a
      statistically significant decrease in asthma symptoms, day and night, and the
      need for rescue medication at night. All doses were well-tolerated. In
      conclusion, the lowest effective dose in this study was formoterol Turbuhaler 6
      microg b.i.d.

PMID- 8866595
TI  - Salmeterol versus formoterol in patients with moderately severe asthma: onset and
      duration of action.
AB  - We evaluated the profile of the bronchodilatory effect of three inhaled beta2
      agonists, 24 microg formoterol, 50 microg salmeterol and 200 microg salbutamol,
      in patients with stable, moderately severe asthma. Thirty asthmatics (mean+/-SD
      age 54+/-8 yrs; forced expiratory volume in one second (FEV1) 58+/-12% predicted;
      reversibility of FEV1 21+/-8% from baseline) participated in a single-centre,
      double-blind, randomized, single-dose, cross-over study. FEV1 was obtained in
      baseline condition and 10, 20, 30, 60 min, and every hour up to 12 h after
      inhalation of the trial drug. Specific airway conductance (sGaw) was measured at
      baseline condition and 1, 3, 5, 7, 10, 20, 30, 60 min, and every hour up to 12 h
      after inhalation. Formoterol produced a mean increase in sGaw (as % of baseline)
      of 44% after 1 min, maximal (135%) after 2 h, and 56% after 12 h. The mean
      increase in FEV1 was maximal (27%) after 2h, and 10% after 12 h. After
      salmeterol, mean increase in sGaw amounted to 16% after 3 min, maximal (111%)
      after 2-4 h, and 58% after 12 h. The mean increase in FEV1 was maximally 25%
      after 3h, being 11% after 12 h. After salbutamol, mean increase in sGaw was 44%
      after 1 min and maximal (100%) after 30 min. The peak increase in FEV1 was 25%.
      We conclude that formoterol (24 microg) and salmeterol (50 microg) had an equal
      bronchodilatory capacity, which was similar to that of 200 microg salbutamol and
      lasted for at least 12 h in patients with asthma. However, formoterol had a more
      rapid onset of action than salmeterol, equal to that of salbutamol.

PMID- 8866596
TI  - Comparison of inhaled salmeterol and individually dose-titrated slow-release
      theophylline in patients with reversible airway obstruction. European Study
      Group.
AB  - The aim of this study was to compare the clinical efficacy of salmeterol versus
      theophylline in the treatment of moderate-to-severe asthma. One hundred and
      eighty nine asthmatic patients (forced expiratory volume in one second (FEV1) or
      peak expiratory flow (PEF) >50% of predicted) were randomized to receive either
      salmeterol dry powder, 50 microg b.i.d. via a Diskhaler (n=92) or dose-titrated
      slow-release theophylline capsules ("Theo-Dur") b.i.d. (n=97), in a double-blind,
      double-dummy, parallel group study for 4 weeks. Patients had previously been
      titrated with theophylline to a serum theophylline level of 10-20 microg x mL-1.
      The median percentage of nights with no asthma symptoms rose from 14% in both
      groups at baseline to 71% with salmeterol and to 46% with theophylline (p=0.044).
      There was also a significant increase for salmeterol in the median percentage of
      nights with no rescue salbutamol use (from 36 to 86%) compared with theophylline
      (from 71 to 78%; p=0.002). The mean morning PEF increased from 337 L x min-1 in
      the salmeterol group and 332 L x min-1 in the theophylline group to 372 and 357 L
      x min-1, respectively. No significant difference between the two treatments was
      observed for PEF, symptoms or additional salbutamol medication during the day.
      The incidence of gastrointestinal symptoms (gastric irritation, nausea and
      vomiting) was greater among patients receiving theophylline (11%) than with
      salmeterol (3%). These findings suggest that inhaled salmeterol is more effective
      in relieving symptoms of asthma, and better tolerated than theophylline in
      patients with moderate-to-severe asthma.

PMID- 8866597
TI  - Increased bronchial responsiveness to exercise as a risk factor for symptomatic
      asthma: findings from a longitudinal population study of children and
      adolescents.
AB  - The prevalence of asthma seems to be on the increase and risk factors are not
      well-established. To investigate the relationship between asymptomatic increased
      bronchial responsiveness to exercise (BRE) and subsequent development of asthma,
      we studied a population sample of children and adolescents, aged 7-17 yrs at
      enrollment, examined twice 6 yrs apart (54 and 68%, respectively, of the original
      sample participated in the two examinations). Complete information was available
      for 383 subjects (191 males and 192 females). Case history and questionnaire data
      were obtained and were used to assess the presence or absence of symptomatic
      asthma. Exercise testing, performed at enrolment only, consisted of steady
      running on a 10% sloping treadmill for 6 min in a climate chamber. BRE was
      recorded as percentage fall in forced expiratory volume in one second (FEV1) from
      pre-exercise FEV1, within 15 min after exercise. Twenty subjects (5%) had asthma
      at enrolment, whereas 58 subjects (15%) had current asthma (i.e. symptoms within
      the preceding 12 months) at the time of follow-up, of whom 40 were asymptomatic
      at enrolment (new asthma). In general, increased BRE at enrolment was
      significantly associated with symptomatic asthma at follow-up. Analysing the data
      for subjects who were asymptomatic at enrolment (n=363), showed that new asthma
      at follow-up was not predicted by increased BRE at enrolment, whether BRE was
      evaluated as a continuous (R2=0.06, p=0.13) or dichotomous (cut-off: BRE =10%
      decline in FEV1; odds ratio (OR) 0.8 (0.4-1.2); p=0.11) variable. However, the
      data do not exclude the possibility that asymptomatic subjects with BRE >15% have
      an increased risk for subsequent development of asthma. The findings of the
      present study suggest that increased bronchial responsiveness to exercise in
      asymptomatic children and adolescents is not a strong predictor for subsequent
      development of symptomatic asthma. Further studies, preferably of larger samples,
      are needed to confirm these findings.

PMID- 8866598
TI  - Early and late allergic reaction in the nose assessed by whole body
      plethysmography.
AB  - Physiological changes during late phase nasal responses after allergen challenge
      are difficult to establish and different criteria are used for the definition of
      a positive late phase nasal reaction. The objective of this study was to assess
      the value of whole body plethysmography in detecting changes in nasal airway
      resistance after allergen challenge and to suggest criteria for the definition of
      early and late phase nasal reactions. Nasal challenge with allergen was performed
      in 15 allergic patients. Nasal resistance was followed until 10 h after allergen
      challenge and on a control day using whole body plethysmography. The mean
      percentage changes in the inspiratory nasal resistance during the early phase
      period (0.25-2 h) and the late phase period (4-10 h) were significantly higher on
      the allergen challenge day than on the control day (p=0.001 and p=0.01,
      respectively). The mean percentage change in the inspiratory nasal resistance
      during the early and late phase period on the control day plus 2 times the
      standard deviation served as cut-off point for a positive reaction. Using this
      definition, all patients had early reactions and 7 of the 15 patients (47%) also
      had late reactions. We conclude that whole body plethysmography is a useful,
      noninvasive method for the measurement of the physiological changes in the nose
      following allergen challenge.

PMID- 8866599
TI  - Hormonal treatment in advanced non-small cell lung cancer: fact or fiction?
AB  - In patients with advanced non-small cell lung cancer, cachexia is an important
      cause of morbidity and mortality. The pathogenic mechanism of this finding,
      usually referred to as "cancer anorexia and cachexia syndrome" (CACS), is complex
      and far from completely understood, but a disturbed equilibrium between possible
      food intake and metabolic needs seems to be fundamental. The literature data on
      the treatment options in advanced non-small cell lung cancer (NSCLC) with
      cachexia are reviewed. Based on the clinical studies on cancer cachexia, some
      recommendations for the therapeutic approach of this disorder in patients with
      advanced NSCLC can be given. Metoclopramide is easily administered, can alleviate
      gastric disturbances, but probably does not correct the catabolic spiral of CACS.
      There are not enough data to advise the use of parenteral nutritional support,
      hydrazine, cyproheptadine, tetrahydrocannabinol or nandrolone decanoate.
      Corticosteroids are useful in additional analgesia and fast palliation of very
      weak and debilitated patients in the final episode of their disease. Recent data
      in non-small cell lung cancer patients are in favour of the use of high-dose
      progestagens to improve both appetite and weight.

PMID- 8866600
TI  - The role of the epithelial cell in Escherichia coli induced neutrophil migration
      into the urinary tract.
AB  - Neutrophil influx to mucosal surfaces represents one of the earliest inflammatory
      responses to mucosal infection. We have been studying external interactions with
      urinary tract epithelial cells in an attempt to understand the molecular
      mechanisms behind this process. Uropathogenic Escherichia coli induced urinary
      tract epithelial cells to secrete the neutrophil chemoattractant interleukin-8
      (IL-8). IL-8 secretion was higher in response to isogenic strains expressing type
      1 or P fimbriae that adhered to the epithelial surface. Deliberate colonization
      of the human urinary tract with E. coli induced the local production of IL-8 and
      levels correlated with urinary neutrophil numbers suggesting a role for IL-8 in
      neutrophil migration. E. coli induced neutrophil migration across urinary tract
      epithelial layers in vitro, and this process was blocked with anti-IL-8 antibody.
      IL-8's activity was localized to the epithelial surface. Furthermore, these cells
      were shown to constitutively express IL-8 receptor A and B messenger ribonucleic
      acid (mRNA), suggesting a possible role for IL-8 on epithelial cell function. E.
      coli enhanced the expression of intercellular adhesion molecule-1 (ICAM-1) on
      urinary tract epithelial cells, and neutrophil migration across urinary tract
      epithelial layers in vitro was dependent on epithelial ICAM-1 and neutrophil Mac
      1 (CD11b/CD18) expression. These results suggest that bacterial/epithelial cell
      interactions play a key role in the induction of neutrophil migration during
      mucosal infection, and show the necessity for host-derived chemotactic factors
      and cell adhesion events in E. coli induced transuroepithelial migration in
      vitro.

PMID- 8866601
TI  - Stomach as a source of colonization of the respiratory tract during mechanical
      ventilation: association with ventilator-associated pneumonia.
AB  - The aetiopathogenesis of ventilator-associated pneumonia (VAP) requires abnormal
      oropharyngeal and gastric colonization and the further aspiration of their
      contents to the lower airways. VAP develops easily if aspiration or inoculation
      of microorganisms occur in patients with artificial airways, in whom mechanical,
      cellular and/or humoral defences are altered. Well-known risk factors for gastric
      colonization include: alterations in gastric juice secretion; alkalinization of
      gastric contents; administration of enteral nutrition; and the presence of
      bilirubin. However, the role of the colonized gastric reservoir in the
      development of VAP remains debatable. Evidence in favour of the role of the
      stomach in the development of VAP comes mainly from randomized, controlled trials
      of selective gut decontamination and stress ulcer prophylaxis in the intensive
      care unit (ICU), in which reducing the bacterial burden of the stomach decreases
      the incidence of nosocomial respiratory infections. However, at least three
      studies of flora have found an absence of stomach origin of pneumonia occurring
      during mechanical ventilation. Prophylactic measures suggested to prevent VAP in
      relation to the gastric reservoir include: treatment for stress ulcers with
      sucralfate; prevention of duodenal reflux with metoclopramide; reduction of
      gastric burden and bacterial translocation by selective digestive
      decontamination; acidification of enteral feeding; and jejunal feeding. Gastro
      oesophageal reflux can be prevented by using small bore nasogastric tubes and
      jejunal feeding. The aspiration of gastric contents can be reduced by positioning
      patients in a semirecumbent position, checking the patency of the tube cuff, and
      aspiration of subglottic secretions. The role of the stomach as a reservoir for
      microorganisms causing ventilator-associated pneumonia is still controversial but
      despite the debate, there is major evidence in the literature in favour of the
      gastric origin of part of these pulmonary infections.

PMID- 8866602
TI  - Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung
      damage or inflammation.
AB  - This review describes the usefulness of monitoring the activity level of lactate
      dehydrogenase (LDH) and its isoenzyme pattern as indicators of pathological
      conditions in the lungs, such as cell damage or inflammation. Cytoplasmatic
      cellular enzymes, like LDH, in the extracellular space, although of no further
      metabolic function in this space, are still of benefit because they serve as
      indicators suggestive of disturbances of the cellular integrity induced by
      pathological conditions. Since LDH is an enzyme present in essentially all major
      organ systems, serum LDH activity is abnormal in a large number of disorders.
      Although the increase in total serum LDH activity is rather nonspecific, it is
      proposed that measurement of LDH activity levels and its isoenzyme pattern in
      pleural effusion and, more recently, in bronchoalveolar lavage fluid may provide
      additional information about lung and pulmonary endothelial cell injury.

PMID- 8866603
TI  - Detection of herpesvirus-like DNA in the bronchoalveolar lavage fluid of patients
      with pulmonary Kaposi's sarcoma.
AB  - Pulmonary involvement is a clinically important form of visceral Kaposi's sarcoma
      in immunocompromised patients. Recently, herpesvirus-like deoxyribonucleic acid
      (DNA) sequences, defining a new herpesvirus termed "human herpesvirus 8" (HHV8)
      or "Kaposi's sarcoma-associated herpesvirus" (KSHV), were detected in Kaposi's
      sarcoma of acquired immune deficiency syndrome (AIDS) and non-AIDS patients. We
      describe the successful detection of HHV8 DNA in the bronchoalveolar lavage (BAL)
      fluid of patients with pulmonary Kaposi's sarcoma. Three immunocompromised
      patients, two HIV seropositive and one after kidney transplantation, suffered
      from respiratory symptoms and showed pulmonary infiltrates on chest radiography
      after development of biopsy proven Kaposi's sarcoma of the skin. Bronchoscopy
      revealed the typical Kaposi like livid endobronchial lesions. BAL fluid was
      analysed for the presence of HHV8 DNA using a nested polymerase chain reaction
      (PCR) assay. HHV8 DNA was detected in the BAL fluid of all three patients. In
      addition, HHV8 DNA could be detected in the skin biopsy tissue, lymph node, and
      peripheral blood mononuclear cells of these patients. Our data show that human
      herpesvirus 8 deoxyribonucleic acid can be detected in the bronchoalveolar lavage
      fluid of patients with pulmonary Kaposi's sarcoma. If further studies reveal a
      high specificity for human herpesvirus 8 deoxyribonucleic acid detection, this
      test will improve the tools for the diagnosis of pulmonary Kaposi's sarcoma
      without further need of biopsies.

PMID- 8866604
TI  - Frequency dependence of specific airway resistance in a commercialized
      plethysmograph.
AB  - Specific airway resistance (sRaw) measured by body plethysmography has been shown
      to decrease markedly with decreasing breathing frequency when the inspired air is
      not conditioned to body temperature, atmospheric pressure and saturation with
      water vapour (BTPS). The phenomenon has been attributed to noninstantaneous gas
      warming and wetting in the airways. The aim of this investigation was to assess
      whether the phenomenon was also present in a commercialized plethysmograph
      featuring an "electronic BTPS correction". Airway resistance (Raw) and sRaw were
      measured in 15 healthy subjects at six breathing frequencies ranging 0.25-3 Hz,
      using a constant volume plethysmograph in which a correction for non-BTPS gas
      conditions was applied by electronically flattening the box pressure-airway flow
      loop (Jaeger Masterscreen Body, version 4.0). The temperature and water vapour
      saturations in the box averaged 26.5 +/- 1.3 degrees C and 59 +/- 6%,
      respectively. Raw and sRaw exhibited a clear positive frequency dependence in all
      but one subject. From 0.25 to 3 Hz Raw increased from (mean+/-SD) 0.62 +/- 0.55
      to 1.71 +/- 0.76 hPa x s x L-1 (p<0.001), and sRaw from 2.34 +/- 1.90 to 7.55 +/-
      3.08 hPa x s (p<0.001). The data are consistent with a simple model, in which gas
      conditioning in the airways and external dead space occurred with a time constant
      of 0.39 s. We conclude that the electronic BTPS correction of the instrument was
      inadequate, probably because it is assumed that gas conditioning in the airways
      is instantaneous. We recommend that, with similar instruments, airway resistance
      be measured using as high a panting frequency as feasible.

PMID- 8866605
TI  - Disseminated mucormycosis presenting with lower extremity weakness.
AB  - Mucormycosis is an uncommon, but important opportunistic fungal infection. The
      most commonly reported areas of infection are pulmonary, rhinocerebral and
      cutaneous. It has only rarely been reported to cause peripheral neurological
      symptoms. This report presents the case of a patient who presented with ascending
      paralysis due to pulmonary mucormycosis. The presentation is believed to be due
      to a lesion which abutted the vertebral column and caused infarction of the
      spinal cord.

PMID- 8866606
TI  - M. Kansasii pulmonary disease in idiopathic CD4+ T-lymphocytopenia.
AB  - Cases of patients with markedly depressed CD4+ T-lymphocyte counts, with or
      without opportunistic infections, in the absence of any evidence of human
      immunodeficiency virus (HIV) have been described in recent years. In 1992, the
      definition of "idiopathic CD4+ T-lymphocytopenia" was formulated by the Centers
      for Disease Control and Prevention (CDC) of Atlanta (USA). The present case
      illustrates the occurrence of an unexplained Mycobacterium kansasii pneumonia in
      a white HIV-negative subject with a persistent depletion of CD4+ T-lymphocytes
      and suppression of cell-mediated immunity. To our knowledge, this is the first
      observation of idiopathic CD4+ T-lymphocytopenia with pulmonary mycobacteriosis
      due to Mycobacterium kansasii, and the sixth case of this kind of
      immunodeficiency described in Italy.

PMID- 8866607
TI  - Atypical mycobacteriosis as a complication of talc pneumoconiosis.
AB  - A 57 year old man, receiving compensation for talc pneumoconiosis since 1977, was
      admitted to hospital for the first time in 1987, with symptoms of weight loss,
      fever, dyspnoea and productive cough. A chest roentgenogram showed bilateral
      cavitation. Two years later, Mycobacterium xenopi was found in sputum cultures.
      Despite specific oral antibiotherapy, the patient's health deteriorated and he
      died in 1990. To the best of our knowledge, this is the first reported case of an
      association of talcosis with a M. xenopi pneumonia. The relative timing of the
      two diseases suggests that talc pneumoconiosis predisposed to the infection by M.
      xenopi.

PMID- 8866608
TI  - Pulmonary hypertension associated with POEMS syndrome.
AB  - Pulmonary hypertension (PH) is an uncommon but lethal complication of some
      connective tissue diseases. We describe two cases of PH associated with plasma
      cell dyscrasia, with polyneuropathy (P), organomegaly (O), endocrinopathy (E), M
      protein (P) and skin changes (S) described as POEMS syndrome. Two patients, one
      female and one male, were hospitalized for dyspnoea. Both had a history of POEMS
      syndrome a few years previously. PH was diagnosed from cardiac catherization, and
      complete investigations did not reveal other underlying disease. In Case No. 1,
      mean pulmonary artery pressure was 40 mmHg and pulmonary vascular resistance was
      775 dyne x s x cm-5 x m2, with a significant reversibility to vasodilators.
      Nifedipine and fluindrone treatment was initiated. The patient was still alive 18
      months later. In Case No. 2, mean pulmonary artery pressure was 28 mmHg and
      pulmonary vascular resistance was 243 dyne x s x cm-5x m2, with a slight
      reversibility to vasodilators. The patient died 6 months later. Our observations
      suggest that pulmonary hypertension (PH) may be associated with the POEMS
      syndrome, and that patients suffering from the POEMS syndrome and dyspnoea should
      be tested for PH.

PMID- 8866609
TI  - Tuberculin conversion and abnormal chest radiograph in an infant.

PMID- 8866610
TI  - Variability in airway inflammation sampled by bronchoalveolar lavage.

PMID- 8866611
TI  - Botulinum versus tetanus neurotoxins: why is botulinum neurotoxin but not tetanus
      neurotoxin a food poison?
AB  - Botulinum and tetanus neurotoxins, produced by Clostridium botulinum and
      Clostridium tetani, respectively, are the most poisonous poisons known to
      mankind. Although botulinum and tetanus neurotoxins share several
      characteristics, such as similar mol. wts, similar macrostructure, virtually
      identical mode of action, and a strong amino acid sequence homology, the two
      neurotoxins differ in one very significant way; only botulinum neurotoxin is a
      food poison. Factors responsible for the food poisoning potential of botulinum
      neurotoxins seem to be a group of complexing proteins that are also produced by
      C. botulinum, and are known to associate with the neurotoxin. Translation
      products of nucleotide sequences upstream to the neurotoxin genes of serotypes A,
      B, C, D, E and F botulinum neurotoxin reveal the location of genes for one of the
      complexing proteins that could be transcribed as polycistronic mRNA to include
      neurotoxin sequences. No such protein seems to be present in C. tetani,
      suggesting that the lack of complexing proteins might be responsible for tetanus
      not being a food poison.

PMID- 8866612
TI  - A microinjection technique using Drosophila melanogaster for bioassay-guided
      isolation of neurotoxins in arthropod venoms.
AB  - Modern analytical techniques permit isolation and structural determination of
      neurotoxins at the picomole level. However, bioassay-guided fractionation of the
      sample often relies on simple injection assays using insects, vertebrates or
      crustaceans of a fairly large size, thus consuming quite a large amount of the
      samples being investigated. In order to investigate samples of very small size,
      we have devised an insect microinjection method using glass micropipettes and
      Drosophila melanogaster adults as test insects. The validity of the method was
      tested with a series of six buthoid scorpion venoms (Androctonus australis,
      Buthotus judaicus, Buthus tamulus, Centruroides sculpturatus, Leiurus
      quinquestriatus hebraeus, Tityus serrulatus) and one chactoid scorpion (Scorpio
      maurus palmatus) as standards. The LD50S of the venoms were determined using both
      the microinjection method and a classical injection assay with crickets (Gryllus
      bimaculatus) as test insects. Results demonstrated that the new method can
      successfully be applied to the study of insect neurotoxic activity in arthropod
      venoms. The Gryllus:Drosophila ratio in amount of sample utilized is 100.
      However, for all Buthoid venoms tested, except L. quinquestriatus, Drosophila
      showed less sensitivity, thus reducing the gain by a factor of 2-10. Drosophila
      were several times more sensitive to the only chactoid venom tested. These
      results clearly demonstrate the advantage of using this microtechnique, when
      limited amounts of material are available for both chemical and biological work.

PMID- 8866613
TI  - Production and characterization of monoclonal antibodies against stonustoxin from
      Synanceja horrida.
AB  - Stonustoxin (SNTX), a lethal factor purified from the venom of stonefish
      Synanceja horrida, is a protein (148,000 mol. wt) existing as a dimer comprising
      two subunits (alpha and beta) of mol. wts 71,000 and 79,000, respectively. Its
      LD50 (i.v.) is 17 ng/g in mice and it causes haemolysis of rat and rabbit
      erythrocytes in vitro. Eight monoclonal antibodies (Mabs) against SNTX have been
      developed using the Balb/C mouse. These Mabs have been purified by Protein G
      affinity membrane disc chromatography. They were all classified as IgG1 with half
      of them having kappa and the rest lambda light chains. They had affinity
      constants ranging from 3.75 x 10(-9) to 9.74 x 10(-9) M. Six were able to protect
      mice from a challenge of a lethal dose of SNTX. However, not all protective Mabs
      were able to neutralize the haemolytic effect in vitro. Only four Mabs (31A, 32B,
      38A and 46A) could inhibit rat and rabbit erythrocyte haemolysis, while one Mab
      (43D) offered partial inhibition and another Mab (8A) did not inhibit haemolysis
      at all. The non-protective Mabs (43B and 44G) were also incapable of neutralizing
      haemolysis. Five epitopes were recognized by the eight Mabs. Four Mabs (31A, 32B,
      38A and 46A) were found to have similar epitope specificity while the rest were
      directed at different epitopes on the SNTX molecule. Thus these results suggest
      that the domain on the SNTX molecule responsible for lethality is probably
      distinct from the domain important for in vitro haemolytic activity.

PMID- 8866614
TI  - Presynaptically acting snake venom phospholipase A2 enzymes attack unique
      substrates.
AB  - Synaptosomes were incubated with bovine serum albumin (BSA) to examine whether
      the presynaptic action of snake venom phospholipase A2 (PLA2) toxins is due
      either to the release of fatty acids resistant to extraction by BSA or to the
      liberation of a specific fatty acid type. In the presence of BSA (0.5% or 1.0%)
      two PLA2 enzymes from Naja naja atra and Naja naja kaouthia snake venoms that do
      not have a predominant presynaptic action at the neuromuscular junction (PS-) did
      not stimulate acetylcholine (ACh) release from synaptosomes. In contrast, two
      PLA2 enzymes (beta-bungarotoxin, scutoxin) that do have a predominant presynaptic
      action at the neuromuscular junction (PS+) did stimulate ACh release. BSA did not
      antagonize PS- enzymes by more efficiently extracting the fatty acids produced by
      these enzymes relative to PS+ enzymes. While absolute amounts of total and
      unsaturated fatty acid produced overlapped for the PS- and PS+ enzymes, the two
      PS+ enzymes produced a significantly greater absolute amount and relative
      percentage of palmitic acid (16:0) than did either of the PS- enzymes. However,
      the levels of free palmitic acid remaining in the synaptosomes where they would
      exert effects on ACh release were similar for the N. n. kaouthia PLA2 (PS-) and
      beta-bungarotoxin (PS+). Therefore, the total (supernatant plus synaptosomal)
      amount of palmitic acid produced per se did not account for stimulation of ACh
      release, since the greater amounts produced by the PS+ enzymes were removed from
      the synaptosomes by BSA. The production of higher levels of palmitic acid
      suggests either that PS+ enzymes gain access to sites containing phospholipid
      substrates unavailable to the PS- enzymes, or that they have a different
      substrate preference. These findings suggest new possibilities for the mechanism
      of PS+PLA2 action, including site-directed enzymatic activity and protein
      acylation.

PMID- 8866615
TI  - A new saxitoxin analogue from a xanthid crab Atergatis floridus.
AB  - A novel paralytic toxin was isolated from toxic specimens of a xanthid crab
      Atergatis floridus inhabiting the Pacific coast of Shikoku Island. Its structure
      was deduced to be 11-saxitoxinethanoic acid (SEA) based on high-performance
      liquid chromatography, electrospray ionization mass spectrometry, and 1H and 13C
      NMR spectrometries. This acid was assumed to exist as an equilibrium mixture of
      three tautomers, the main tautomer being the hydrate form 11 beta-epimer. SEA
      showed a specific toxicity of 830 mouse units per mumole on i.p. injection into
      mice.

PMID- 8866616
TI  - The role of enzymatic activity in inhibition of the extrinsic tenase complex by
      phospholipase A2 isoenzymes from Naja nigricollis venom.
AB  - Three phospholipase A2 isoenzymes from Naja nigricollis venom inhibit the
      extrinsic tenase complex. We examined the role of their enzymatic activity in
      this inhibition by studying the effects of native and His-modified enzymes. Only
      CM-IV of the His-modified, catalytically inactive proteins showed significant
      inhibition of the activity of the complex. This indicates that strongly
      anticoagulant CM-IV inhibits the complex by both enzymatic and nonenzymatic
      mechanisms, whereas the weakly anticoagulant isoenzymes, CM-I and CM-II, inhibit
      primarily by catalytic degradation of phospholipids. This indicates a functional
      difference in the mode of inhibition between strongly and weakly anticoagulant
      phospholipase A2 enzymes.

PMID- 8866617
TI  - Detection of diarrhoetic shellfish toxins in mussels from Italy by ionspray
      liquid chromatography-mass spectrometry.
AB  - Direct detection of okadaic acid (OA), dinophysistoxin-1 (DTX-1) and some of
      their related compounds in toxic mussels (Mytilus galloprovincialis) is reported
      using ionspray liquid chromatography-mass spectrometry (LC-ISP-MS). This was
      employed to analyse diarrhoetic shellfish poisoning (DSP) toxins in mussels
      collected from coastal areas of the northern and southern Adriatic Sea. DTX-1 was
      found in some samples from both the northern and southern Adriatic and this is
      the first report of the unambiguous identification of this toxin in Italian
      mussels. The low levels found indicate that this toxin did not play a significant
      role in toxicity in these samples. Okadaic acid was found in all the mussels
      examined, although its concentration was not always sufficient to account for DSP
      toxicity. Furthermore, two related compounds of OA were detected in all the
      samples and one related DTX-1 compound was observed in some samples from the
      northern Adriatic. All three compounds are still to be identified, but it is
      possible that these substances are involved in mussel DSP toxicity in the
      Adriatic Sea.

PMID- 8866619
TI  - Stability of microcystins from cyanobacteria--II. Effect of UV light on
      decomposition and isomerization.
AB  - Microcystins are very potent hepatotoxins and strong liver tumor promoters
      produced by cyanobacteria, and their occurrence has been reported all over the
      world. They could threaten human health when toxic Microcystis occurs in water
      supply reservoirs. In this study, we examined the stability of microcystins
      during photolysis with UV light. The toxins were easily decomposed by UV light at
      wavelengths around the absorption maxima of the toxins and the decomposition
      depended on the intensity of the light. The half-life of microcystin LR by 147
      microW/cm2 UV irradiation was 10 min, and the toxin was completely decomposed by
      2550 microW/cm2 UV after 10 min. When the toxins were irradiated with weaker UV
      light, isomerization was also observed by a different mechanism from that during
      photolysis by sunlight and pigment, and several products including three
      geometrical isomers of the conjugated diene of Adda were detected. Microcystin RR
      showed almost the same behavior as that of microcystin LR under the same
      conditions. Since no noxious products were formed in the present study, a water
      treatment including UV irradiation is very possible for removing microcystins
      from raw water.

PMID- 8866618
TI  - Enhancement of plasma fibrinolysis in vitro by jararhagin, the main haemorrhagic
      metalloproteinase in Bothrops jararaca venom.
AB  - Jararhagin, a haemorrhagic metalloproteinase from Bothrops jararaca venom, plays
      an important role in systemic as well as local haemorrhage. In this study, the
      effect of jararhagin on the fibrinolytic system was investigated. The
      fibrinolytic activity of various kinds of animal plasmas was measured by the
      fibrin plate method. No activity was detected in plasma alone. However, after
      mixing plasma with jararhagin, strong fibrinolytic activity was recorded in
      guinea-pig, horse, dog, rabbit and human plasmas. The mechanism of the increase
      of firbinolytic activity by jararhagin was studied further in guinea-pig plasma.
      Fibrin-zymographic studies indicated that jararhagin increased tissue-type
      plasminogen activator (tPA) activity by the dissociation of a complex of tPA with
      type 1 plasminogen activator inhibitor (PAI-1). alpha 2-Plasmin inhibitor (alpha
      2-PI) activity in the plasma was measured using a synthetic chromogenic substrate
      method after incubation with jararhagin. The alpha 2-PI activity in the plasma
      decreased in both time-dependent and dose-dependent manners. These in vitro
      results suggest that, in some animal plasmas, jararhagin increases plasma
      fibrinolytic activity by causing dissociation of the tPA/PAI-1 complex and by the
      inactivation of alpha 2-PI. It is possible that this direct action of jararhagin
      on the enhancement of plasma fibrinolytic activity may contribute to the
      aetiology of systemic haemorrhage frequently observed in human victims of B.
      jararaca envenoming.

PMID- 8866620
TI  - The effects of two phospholipase A2 inhibitors on the neuromuscular blocking
      activities of homologous phospholipases A2 from the venom of Pseudechis
      australis, the Australian king brown snake.
AB  - Previous studies have shown that homologous phospholipases A2 (PLA2) (Pa-3, Pa
      9C, Pa-10F and Pa-11) from the venom of the Australian king brown snake,
      Pseudechis australis, significantly reduce the resting membrane potentials and
      quantal contents of endplate potentials recorded from endplate regions of mouse
      triangularis sterni nerve-muscle preparations. It is not clear whether PLA2
      activity is essential for their neuromuscular activities. Therefore,
      pharmacological studies were carried out to determine whether neuromuscular
      activity of the toxins changed after treatment with the phospholipase A2
      inhibitors 7,7-dimethyl-eicosadienoic acid (DEDA) and manoalide. After incubation
      of the toxins with manoalide (120 nM), or DEDA (50 microM), no PLA2 activity
      against 1-stearoyl 2-[3H]arachidonoylglycerophosphocholine was detected. After
      incubation with manoalide and/or DEDA, the toxins did not depolarize muscle fibre
      membranes up to 60 min after administration. However, manoalide and DEDA had
      different influences on the inhibitory effect of these toxic enzymes on
      acetylcholine release from nerve terminals. Manoalide abolished the inhibitory
      effect of the toxins on evoked release of acetylcholine. In contrast, DEDA was
      not able to prevent the reduction of quantal content of endplate potentials
      induced by the toxins. This study provides evidence that the depolarizing action
      and the inhibitory effect on release of acetylcholine exerted by these toxic PLA2
      from king brown snake are independent phenomena. The evidence for this conclusion
      was that inhibition of enzymatic activity with an arachidonic acid analogue
      (DEDA) abolished the depolarizing effect of the toxins but not the effects on the
      quantal release of acetylcholine from mouse motor nerve terminals. The data
      suggest that the depolarizing effect of these toxins is probably due to the
      enzymatic activity. Since manoalide interacts with lysine residues of PLA2
      polypeptides, and, as shown here, manoalide prevented inhibition of
      neurotransmitter release, lysine residues may play an important role in the
      inhibitory activity of these toxins.

PMID- 8866621
TI  - Localization and expression of phospholipases A2 in Trimeresurus flavoviridis
      (habu snake) venom gland.
AB  - The localization and expression profiles of phospholipases A2 (PLA2s) in
      Trimeresurus flavoviridis venom gland were studied by means of in situ
      hybridization and immunohistochemical techniques. Venom gland cells are tightly
      arrayed in a single layer along the inlet-like lumens in which venom proteins are
      stored. mRNAs for PLA2s were detected at the high level in cytoplasm. Using the
      immunohistochemical technique with polyclonal anti-Asp-49-PLA2 antibody, Asp-49
      PLA2 and, possibly, its isozymes were detected in intracellular granules and in
      venom lumens. The intracellular granules containing PLA2 proteins appear to be
      transferred from the nucleus towards the outer membrane facing the lumen, and
      then to be secreted.

PMID- 8866622
TI  - Characterization of a hemorrhagic factor, LHF-I, isolated from the bushmaster
      snake (Lachesis muta muta) venom.
AB  - Hemorrhagic factor I (LHF-I) was previously purified from the venom of the
      bushmaster snake (Lachesis muta muta). In terms of biochemical and immunological
      properties, LHF-I is a glycoprotein (mol. wt 100,000, pI 4.7) consisting of two
      subunits; it loses its activity following mercaptoethanol treatment. LHF-I
      contains 0.7 g-atom zinc and 1.2 g-atom calcium per mole protein. The hemorrhagic
      and the proteinase activities are inhibited by EDTA; subsequent addition of Ca2+
      or Mg2+ does not reverse the EDTA-induced inhibition of the hemorrhagic activity.
      The metalloenzyme does not hyrolyze arginine esters and is devoid of
      phospholipase A2 activity. It hydrolyzes the A alpha- > B beta-chain of
      fibrinogen without clot formation and hydrolyzes selectively the alpha-chain of
      fibrin, leaving the B beta- and tau-chains unaffected. Antibodies to the
      hemorrhagic factor in bushmaster venom were produced by immunizing rabbits with
      the purified protein. The antibody was purified by protein-A affinity
      chromatography. This antibody was also used to screen other Crotalinae venom
      samples for immunologically similar epitopes by ELISA assay. The purified
      antibody reacted only with LHF-I and two samples of bushmaster venom from
      different geographical locations.

PMID- 8866623
TI  - Occurrence of tetrodotoxin and paralytic shellfish poison in the Taiwanese crab
      Lophozozymus pictor.
AB  - Paralytic toxicity was detected by tetrodotoxin (TTX) bioassay in all 15
      specimens of the xanthid crab Lophozozymus pictor collected from northern Taiwan
      in 1993. The average toxicity of crab specimens was 921 +/- 231 (mean +/- S.E.)
      mouse units. The toxin of crab was partially purified and then identified. It was
      found that the crab toxin contained TTX and gonyautoxin. The ratio of TTX to
      gonyautoxin for crab toxin was about 9:1.

PMID- 8866624
TI  - Histamine-1 receptor blockade does not prevent nitroglycerin induced migraine.
      Support for the NO-hypothesis of migraine.
AB  - It has previously been shown that in migraine sufferers infusion of glyceryl
      trinitrate (GTN) and histamine causes an immediate headache during the infusion
      and a genuine migraine attack one to several hours after the infusion. This
      identical time profile indicates a common mechanism of action. To evaluate
      whether GTN causes headache via liberation of histamine, we studied the effect of
      GTN 0.5 micrograms.kg-1.min-1 for 20 min in seven migraine sufferers, once after
      pretreatment with the histamine-1 (H1)-receptor blocker mepyramine (0.5 mg.kg-1)
      and once without pretreatment. This mepyramine dose is known to completely
      abolish histamine-induced headache. After pretreatment with mepyramine five
      patients experienced migraine, and without pretreatment six patients did so. The
      median peak headache score was 7 on a 0-10 scale with and without mepyramine
      pretreatment. The arterial responses, evaluated with transcranial Doppler, were
      also unaffected by the mepyramine pretreatment. Our results demonstrate that
      neither headache nor arterial dilatation due to GTN infusion is caused by
      histamine release. In all likelihood the common mediator of migraine induction by
      GTN and histamine is nitric oxide.

PMID- 8866625
TI  - Effect of beta 2-adrenoceptor agonists on plasma potassium and cardiopulmonary
      responses on exercise in patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: The effect of beta 2-adrenoceptor agonist-induced hypokalaemia on
      cardiac arrhythmias might be exacerbated during exercise, especially in patients
      with more compromised airway function. METHODS: To evaluate the effect of beta 2
      adrenoceptor agonists on plasma potassium and cardiopulmonary function during
      exercise, two identical submaximal treadmill exercise tests were performed, at
      least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2
      women, mean age 66 y, mean FEV1/FVC ratio 48.9 (2.8)% 30 min after they had
      received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a
      randomised, double-blind, crossover trial after an initial baseline study with
      vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree
      of breathlessness (Borg scale) were measured before treatment and immediately
      after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored
      continuously before, during and for 30 min after exercise. RESULTS: After the
      saline control, exercise caused an increase in Borg rating (of 4.9), a premature
      ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (
      6.7%), but no significant change in plasma potassium (+0.04 mEq.dl-1), FEV1 or
      QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval,
      Borg scale or VPC frequency at rest, but significantly increased the duration of
      exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared
      to the vehicle control. Following exercise, plasma potassium fell after fenoterol
      by 0.2 mEq.dl-1 and it increased after salbutamol by 0.1 mEq.dl-1 compared to
      baseline levels. Plasma potassium after exercise was significantly lower after
      fenoterol (3.2 mEq.dl-1) compared to the saline control (3.7 mEq.dl-1) and
      salbutamol (3.6 mEq.dl-1). Neither fenoterol nor salbutamol had any significant
      effect on the change in FEV1, oxygen saturation, Borg scale, frequency of VPCs or
      QTc interval during or after exercise compared to the saline control. CONCLUSION:
      When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia
      but no significant difference in cardiopulmonary response in patients with COPD
      during exercise.

PMID- 8866626
TI  - Controlled trial of methotrexate in patients with severe chronic asthma.
AB  - The aim of this study was to investigate the efficacy and adverse effects of
      methotrexate (MTX) in the treatment of severe chronic asthma in 12 patients with
      severe asthma requiring continuous treatment with oral steroids at the Outpatient
      Department of Helsinki University Central Hospital. The study was a randomised,
      double-blind placebo-controlled trial of methotrexate treatment 15 mg weekly on a
      crossover basis over 24 weeks. During the 2 weeks baseline phase the mean dose of
      oral steroids administered was 10.9 (3.2-28) mg.day-1, and the mean dose of
      inhaled steroids administered was 2.3 (1.6-3.2) mg budesonide or beclomethasone.
      The average dose of oral steroids administered was 12.8 mg.day-1 during the last
      2 placebo weeks but only 7.9 mg.day-1 during the last 2 weeks with MTX treatment.
      The reduction in daily dose of oral steroids was 38%, while daily bronchodilator
      use was reduced by 22%. During MTX treatment the patients experienced
      significantly less wheezing, dyspnoea and coughing. Nine out of 12 patients
      reported better asthma control during MTX treatment. The peak expiratory flow
      rate (PEF) 1-s forced expiratory volume (FEV1) values did not differ between MTX
      and placebo treatments. There was no statistical correlation between serum MTX
      concentration and clinical improvement. No serious adverse effects of MTX were
      found during the study. It was concluded that low-dose MTX may be beneficial for
      severe chronic asthma and that this therapy is well tolerated by patients.

PMID- 8866627
TI  - Effects of single oral doses of lysine clonixinate and acetylsalicylic acid on
      platelet functions in man.
AB  - Lysine clonixinate is an analgesic drug with a so far unknown mechanism of
      action. We have determined its effect on platelet cyclooxygenase in man.
      Biosynthesis of thromboxane (TX)B2 and prostaglandin (PG)F2 alpha in clotting
      whole blood ex vivo as well as collagen-induced platelet aggregation measured
      before and at various time points after oral administration of 125 mg lysine
      clonixinate were compared to results obtained with 500 mg acetylsalicylic acid
      (ASA). While biosynthesis of both TXB2 and PGF2 alpha measured
      radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after
      administration of lysine clonixinate, inhibition by ASA was much greater and
      still highly significant after 48 h. Similarly, collagen-induced aggregation of
      platelet-rich plasma was inhibited for a longer period and to a greater extent
      after administration of ASA than after lysine clonixinate. Our results indicate
      that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It
      remains to be investigated whether mechanisms other than inhibition of
      cyclooxygenase contribute to the analgesic activity of lysine clonixinate.

PMID- 8866628
TI  - Effects of hydrochlorothiazide and captopril on lipoprotein lipid composition in
      patients with essential hypertension.
AB  - OBJECTIVE: Effective antihypertensive agents may differ in their capacity to
      reduce cardiovascular risk because they induce potentially atherogenic
      alterations in lipoprotein composition. PATIENTS: To assess this possibility, the
      effects of five months' treatment with either hydrochlorothiazide (HCTZ) or the
      converting enzyme inhibitor captopril (CAPT) on lipoprotein lipid composition
      were compared in thirty normolipidaemic patients with essential hypertension
      (EH). RESULTS: The sixteen patients treated with HCTZ showed the expected
      directional alterations in plasma TG (+31%), HDL2-C (-16%), and CHOL (+7.6%); in
      contrast TG and CHOL were unchanged after captopril in fourteen patients and
      their HDL2-C declined (-16%). Neither drug altered lipoprotein core lipid
      composition, but small increases were observed in the HDL2 sphingomyelin/lecithin
      ratio after both agents. The plasma free (unesterified) cholesterol (FC) lecithin
      (L) ratio, a new index of cardiovascular risk, was abnormally increased before
      treatment and was not altered by either drug. CONCLUSION: These findings indicate
      that HCTZ and CAPT treatment have small, but demonstrable effects on lipoprotein
      surface lipid composition in patients with EH that are confined to the HDL2
      subfraction.

PMID- 8866629
TI  - Effects of pravastatin on plasma and urinary mevalonate concentrations in
      subjects with familial hypercholesterolaemia: a comparison of morning and evening
      administration.
AB  - In order to determine whether there is a difference in the effect of the hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on
      cholesterol synthesis between the morning and the evening, we studied the 24-h
      profile of mevalonate in plasma and urine in 11 subjects with heterozygous
      familial hypercholesterolaemia. In study 1, eight subjects with familial
      hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another
      20-mg dose in the evening after a 1-week wash-out period. In study 2, five
      subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in
      the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash
      out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after
      pravastatin administration in the morning and the evening, respectively. Urinary
      mevalonate excretion was significantly reduced at 4-8 h after pravastatin
      administration in the morning (51 vs 19 nmol.h-1) and at 4-16 h after pravastatin
      administration in the evening (56 vs 27 nmol.h-1). Daily urinary mevalonate
      excretion was equally and significantly reduced by pravastatin in the morning or
      evening. In conclusion, we found that morning and evening administration of
      pravastatin caused equal reductions in plasma and urinary mevalonate
      concentrations.

PMID- 8866630
TI  - Microinjection technique for pharmacological evaluation of microvascular
      permeability in human skin.
AB  - A new technique which combines skin microinjection of minute amounts of drugs
      (0.5 microliter) and measurement of capillary permeability by intravital
      fluorescence videomicroscopy and densitometry is introduced. Glass micropipettes
      with a tip diameter of 7-9 microns are inserted by a micromanipulator into the
      stratum papillare containing the capillary loops and used for microinjection by
      microsyringe and special dispenser. Transcapillary diffusion of sodium
      fluorescein applied by intravenous bolus injection is visualised by fluorescence
      videomicroscopy and stored on videotape. Perivascular fluorescent light intensity
      (FLI) is measured in arbitrary units (AU) by videodensitometry around the site of
      microinjection during playback of the videotapes. The method was tested by
      microinjection of 0.5 microliter histamine (1% solution) at the distal tibial
      plateau. Mean FLI values representing microvascular permeability were 2186 AU 10
      min after microinjection of histamine, 420 AU after physiologic saline and 1228
      AU after histamine combined with oral intake of 20 mg cetirizine. Cetirizine
      significantly reduced (P < 0.01) the increased permeability induced by histamine.
      However, the mean values after injection of the H1-blocker were still
      significantly enhanced (P < 0.01) when compared to the mean values observed after
      injection of physiologic saline solution, which provoked only minor microtrauma.
      The technique offers new scope for pharmacological testing in man.

PMID- 8866631
TI  - Effect of alpha 1-adrenoceptor antagonists, prazosin and urapidil, on a finger
      skin vasoconstrictor response to cold stimulation.
AB  - OBJECTIVES: Cold stimulation causes a finger skin vasoconstrictor response, which
      is regulated by stimulation of alpha-adrenergic receptors and is reduced by
      administration of prazosin. The purpose of this study was to investigate, using a
      laser Doppler flowmeter, whether the decrease in the finger skin vasoconstrictor
      response to cold stimulation produced by administration of two different alpha 1
      adrenoceptor antagonists, prazosin and urapidil, was correlated with the
      corresponding plasma drug concentration, and whether this method could be used to
      evaluate the relative potency of these alpha 1-adrenoceptor antagonists in human
      subjects. METHOD: In thirteen healthy male subjects (20-42 y), finger tip skin
      blood flow was measured during cold stimulation before and 1, 2, 3, 6, and 9 h
      after administration of placebo, prazosin (1 mg) or urapidil (60 mg). RESULTS:
      Both prazosin and urapidil significantly decreased the vasoconstrictor response
      to cold stimulation. The degree of the decrement in the response indicated by the
      reduction ratio was significantly correlated with the plasma concentration of
      prazosin and urapidil. The alpha 1-adrenoceptor blocking activity of prazosin
      estimated by the regression lines was about 130-times more potent than that of
      urapidil. CONCLUSION: These findings suggest that the cold stimulation response
      of finger skin vasoconstriction may be used to evaluate the relative alpha 1
      adrenoceptor blocking potency of drugs.

PMID- 8866632
TI  - Analgesic effects of propyphenazone in comparison to its combination with
      caffeine.
AB  - OBJECTIVE: The aim of the study was to investigate whether the analgesic effect
      of propyphenazone (PROP) was increased when it was administered in combination
      with caffeine (CAFF). METHODS: For assessment of analgesia a model was chosen
      based on chemo-somatosensory event-related potentials (CSSERP) elicited by
      stimulation of the nasal mucosa. Twenty healthy volunteers participated in the
      experiments. The study followed a placebo-controlled, randomised, double-blind, 5
      fold cross-over design. Each of the 5 medications (400 mg PROP, 600 mg PROP, 400
      mg PROP + 100 mg CAFF, 600 mg PROP + 150 mg CAFF, placebo) was orally
      administered. Experiments were separated by at least 5 days. In addition to
      assessment of CSSERP, subjects estimated the intensity of the stimulus. Drug
      effects unrelated to nociception were monitored, and in addition, the plasma
      levels of PROP were also analysed. RESULTS: While 400 mg PROP did not
      significantly reduce the amplitude of CSSERP in comparison to placebo, all other
      medications produced a significant decrease in amplitudes. For both dosages of
      PROP, there was a significant amplification of the antinociceptive effect of PROP
      by CAFF, as indicated by the decrease in CSSERP amplitude. A significant effect
      of the factor "drug" was also found in the spontaneous EEG, indicating an arousal
      reaction after CAFF. No significant differences between plasma levels of PROP
      were found when applied either alone or in combination with CAFF. CONCLUSION: The
      significant increase in the antinociceptive effect of PROP when administered
      together with caffeine appears to be related either to amplification of PROP's
      antinociceptive actions by CAFF or an atinociceptive effect of CAFF itself.

PMID- 8866633
TI  - Effect of dose size on the pharmacokinetics of orally administered quinine.
AB  - Plasma concentrations of quinine were measured by high-performance liquid
      chromatography (HPLC) after oral administration of 250, 500 and 1000 mg base to
      seven healthy adults. The doses were administered after an overnight fast. A
      washout period of at least 21 days was allowed between the doses. Area under the
      plasma concentration-time curve (AUC) for quinine increased in approximate
      proportion to the dose from 250 to 1000 mg. There was also a linear relationship
      between dose and maximum plasma concentration and dose and AUC in individual
      subjects. Time to reach peak plasma concentration remained unchanged over the
      dose range. There was no significant difference in elimination half-life, volume
      of distribution and systemic clearance over the dose range. The occurrence of
      adverse effects was dose and plasma quinine concentration dependent; central
      nervous system side effects increased as dose and plasma concentrations
      increased. These data suggest that after oral administration of quinine, linear
      pharmacokinetics occur in the dose range of 250-1000 mg.

PMID- 8866634
TI  - Influence of age, frailty and liver function on the pharmacokinetics of
      brofaromine.
AB  - OBJECTIVE: The pharmacokinetics of brofaromine, a selective inhibitor of
      monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12
      healthy volunteers (20-35 y). METHODS: Quantitative liver function tests were
      performed to show whether brofaromine elimination in the elderly could be
      predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or
      liver plasma flow (sorbitol clearance). RESULTS: In the elderly the AUC of
      brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9
      mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of
      distribution was smaller (130 vs. 230 l), and the half-life was slightly
      increased (19.0 vs. 14.2 h). No significant correlation was observed between
      hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas
      CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P <
      0.0001). CONCLUSION: Caffeine clearance, a simple, noninvasive test of CYP1A2
      activity, is predictive of brofaromine clearance.

PMID- 8866635
TI  - Inhibition of human thiopurine methyltransferase by furosemide,
      bendroflumethiazide and trichlormethiazide.
AB  - RESULTS: Incubation in vitro of human recombinant and erythrocyte (RBC)
      thiopurine methyl transferase (TPMT) with furosemide, bendroflumethiazide and
      trichlormethiazide demonstrated inhibition of both enzyme preparations, with IC50
      values of 170 microM, 360 microM and 1 mM, respectively. Kinetic studies revealed
      that the inhibition was mixed or non-competitive with regard both to the
      thiopurine substrate 6-mercaptopurine (6-MP) and the methyl donor S-adenosyl-L
      methionine. CONCLUSION: Since S-methylation is a major pathway in the metabolism
      of thiopurines, our data point to the possibility of a clinically significant
      diuretic-thiopurine interaction in patients treated simultaneously with these
      drugs.

PMID- 8866636
TI  - Lack of effect of zinc supplementation on antipyrine clearance in alcoholic liver
      disease.
AB  - METHODS: The effect of zinc supplementation on antipyrine clearance was evaluated
      in 14 outpatients with stable alcoholic liver disease, of whom nine had biopsy
      proven alcoholic cirrhosis. RESULTS: There was no change in antipyrine clearance
      after 14 days of zinc supplementation (median 12.5 vs 12.9 ml.min-1). However, a
      significant increase in P-prothrombin-proconvertin was found. There was a
      positive correlation between S-zinc and antipyrine clearance at inclusion (rs =
      0.76) as well as after zinc supplementation (rs = 0.72). CONCLUSION: No effect of
      zinc supplementation on antipyrine clearance was found. The positive correlation
      between S-zinc and antipyrine clearance could be due to the confounding effect of
      alcoholic liver disease.

PMID- 8866637
TI  - Penetration of pefloxacin and its desmethyl metabolite into the uroepithelium
      after a 800-mg single oral dose in human patients.
AB  - Penetration of pefloxacin into the uroepithelium was studied in 20 patients (10
      men and 10 women) receiving a single oral dose of 800 mg. Samples of serum,
      urine, and uroepithelium were taken 1.8 h (mean) after the dose. Pefloxacin and
      its active metabolite, norfloxacin, were assayed by liquid chromatography, and
      the microbiologically active compounds were quantified by a microbiological
      assay. Both procedures were correlated (r > 0.7); nevertheless, slight
      differences detected in concentrations depended on the levels of norfloxacin
      achieved in the biological samples. The serum and tissue concentrations were
      higher than the concentration of bactericide (4 micrograms.ml-1), except in one
      case. The uroepithelium concentration of pefloxacin was proportional to the serum
      concentration (r = 0.79). The urinary concentrations ranged from 1.2
      micrograms.ml-1 to 82.4 micrograms.ml-1. The mean norfloxacin/pefloxacin ratios
      were 3% in serum, 8% in uroepithelium, and 44% in urine. The mean
      uroepithelium/serum concentration ratios were 1 for pefloxacin and 2.3 for
      norfloxacin. This result shows that, at a time close to that of the maximum
      concentration, there is good penetration of pefloxacin and norfloxacin into the
      uroepithelium.

PMID- 8866638
TI  - Estimation of steady state antibiotic concentration in cerebrospinal fluid from
      single-dose kinetics.
AB  - OBJECTIVE: Assuming linear kinetics, the mean CSF concentrations of an
      antibacterial in steady state (CssCSF) can be estimated, when the area under the
      concentration-time curve in CSF after the first dose is known. For this purpose
      we propose the function CssCSF = AUCCSF.Anticipated dose/Dosing Interval. Applied
      dose. RESULTS: Together with the MIC and MBC of the causative pathogen, the
      estimate is of value in the choice of antibacterial drug and the dosing regimen
      in central nervous system infections.

PMID- 8866639
TI  - Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous
      injection of increasing doses.
AB  - OBJECTIVE: The concentration-time profiles of specific metabolites of moxisylyte,
      an alpha-adrenoceptor blocking agent, in the plasma and urine from 18 healthy
      volunteers were investigated after intracavernous (IC) administrations at three
      dose levels (10, 20 and 30 mg). RESULTS: Four metabolites, unconjugated desacetyl
      moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM)
      sulphates were found in plasma and urine. For all metabolites, t1/2 elimination
      was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for
      DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and
      AUC increased in direct proportion to dose, except for the inactive DAM
      glucuronide. Any the differences detected were small and equivalence of the three
      doses can be accepted. CONCLUSION: The pharmacokinetics of moxisylyte in humans
      following intracavernous administration were linear in the dose range 10 to 30
      mg.

PMID- 8866640
TI  - Pharmacokinetic interaction between diltiazem and nortriptyline.
AB  - OBJECTIVE: Case report of a pharmacokinetic interaction between diltiazem and
      nortriptyline. METHODS: Determination of plasma nortriptyline concentrations by
      HPLC. Calculation of nortriptyline clearances and half-life by formulae used
      routinely in therapeutic drug monitoring. RESULTS: The average plasma
      concentration of nortriptyline at steady state (Css) divided by the amount of
      nortriptyline administered per time rose significantly in a patient with
      concomitant administration of diltiazem, suggesting increased bioavailability
      and/or decreased clearance of nortriptyline. CONCLUSIONS: There is a significant
      pharmacokinetic interaction between diltiazem and nortriptyline, which is
      probably due to a reduction in the first pass clearance of nortriptyline, leading
      to an increase in its bioavailability.

PMID- 8866641
TI  - Elimination half-life of vitamin K1 in neonates is longer than is generally
      assumed: implications for the prophylaxis of haemorrhaghic disease of the
      newborn.

PMID- 8866642
TI  - Immunohistochemical distribution of calcitonin gene-related peptide in nerve
      fibres of the anterior buccal gland of the rat.
AB  - Calcitonin gene-related peptide immunoreactive (CGRP-IR) nerves in rat were
      studied as to their distribution and origin in anterior buccal glands, which are
      unique minor mucous salivary glands in the rat. A moderate number of CGRP-IR
      nerve fibres were located, mostly perivascularly and around intralobular ducts,
      but they were also found around acini. The latter fibres were mainly of sensory
      origin, as suggested by their disappearance after denervation of the ophthalmic
      and maxillary branches of the trigeminal nerve. On the contrary, CGRP-IR nerves
      around interlobular ducts and some of those in a perivascular location remained
      both after sensory denervation and after extirpation of the sympathetic superior
      cervical ganglion. Whether these fibres originate in dorsal root ganglia C3-C4 or
      represent parasympathetic fibres is not known. Based on the present data and the
      previous findings showing a regulatory role of CGRP both on blood and salivary
      flow, it is possible that CGRP in sensory, and possibly also in parasympathetic
      nerves, participates in the regulation of reflex blood flow and salivary
      secretion in the anterior buccal gland of the rat.

PMID- 8866643
TI  - Distribution of concanavalin A and wheat germ agglutinin binding sites in the rat
      peripheral nerve fibres revealed by lectin/glycoprotein-gold histochemistry.
AB  - The affinity of rat peripheral nerve fibres for concanavalin A (Con A) and wheat
      germ agglutinin (WGA) was tested in semi-thin sections of Epon-embedded material.
      A two-step post-embedding technique was used. As a first step, Con A and WGA were
      used in pure form. As a second step, peroxidase-gold (for Con A) and ovomucoid
      gold (for WGA) complexes were applied. The lectin-binding sites, visualized by
      means of signal amplification with the photochemical silver reaction, were
      associated mainly with the myelin sheaths and the surfaces of Schwann cells.

PMID- 8866644
TI  - Histochemical analysis of insulin-like growth factor-1 binding sites in mouse
      normal and experimentally induced arthritic articular cartilage.
AB  - Insulin-like growth factor-1 (IGF-1) plays a key role in regulation of
      chondrocyte metabolism. We examined the localization of IGF-1 binding sites on
      chondrocytes in cartilage from normal and experimentally induced arthritic mouse
      knee joints. Cryostat sections from patellar cartilage were incubated either with
      IGF-1 receptor antibody or biotinylated IGF-1. Subsequently confocal laser
      scanning microscopy was applied to compare the two staining procedures
      qualitatively and quantitatively. This approach allowed detailed analysis of
      membrane-associated and intracellular staining. Using IGF-1 receptor antibody,
      IGF-1 receptors were found on the cell membrane of chondrocytes in the middle and
      deeper cartilage zones, whereas intracellular staining was highest in
      chondrocytes of superficial zones. After incubation with biotinylated IGF-1,
      distinct membrane staining was not present and fluorescence was localized
      homogeneously in the middle and deeper zones but not in superficial zones. In
      cartilage from inflamed knee joints staining with the use of IGF-1 receptor
      antibody did not change significantly, whereas a pronounced increase in staining
      was noted with biotinylated IGF-1 in chondrocytes of the middle and deeper zones
      of cartilage. It is concluded that the staining patterns obtained with the use of
      IGF-1 receptor antibody and biotinylated IGF-1 are remarkably different,
      suggesting that the latter also detects IGF-binding proteins. The results suggest
      that joint inflammation has no consistent effect on IGF-1 receptor expression but
      may induce a significant upregulation of IGF-binding proteins in chondrocytes of
      the middle and deeper zones of cartilage.

PMID- 8866645
TI  - Glucose-6-phosphate dehydrogenase activity in spinach as measured by image
      analysis: a new approach for plant enzyme histochemistry.
AB  - A relatively low-cost computer-assisted image analysis system is described.
      Software has been specifically written for the continuous monitoring of
      absorbance readings on cryostat sections of plant tissues incubated in media to
      reveal enzyme activities. The equipment was tested by quantifying glucose-6
      phosphate dehydrogenase activity in cryostat sections from shoot apices of
      spinach plants. The reaction rate of the dehydrogenase activity was monitored at
      two incubation temperatures, 20 degrees C and 30 degrees C. Control incubations
      were performed in media lacking substrate. The specific test minus control
      reaction at 30 degrees C was twice that at 20 degrees C. Variation of the
      substrate concentration at 30 degrees C yielded a Km value of 0.37 mM. These
      preliminary results show that our image analysis system can be used for kinetic
      measurements of dehydrogenase activity in frozen tissue sections and constitute a
      new approach for enzyme histochemistry in the shoot apical meristem.

PMID- 8866646
TI  - Ontogeny of sulphated glycoconjugate-producing cells in the rat fundic gland.
AB  - The ontogeny of sulphated glycoconjugate-producing cells in the rat fundic gland
      has been studied using high iron diamine (HID), Alcian Blue (AB) at pH 1.0, high
      iron diamine in combination with Alcian Blue at pH 2.5 (HID-AB), cationic
      colloidal gold (CCG) at pH 1.0 under light microscopy and CCG (1.0), HID
      thiocarbohydrazide (TCH)-silver proteinate (SP)-physical development (PD) under
      electron microscopy. From day 19.5 of gestation, sulphated glycoconjugate
      producing cells were discernible under both light and electron microscopy. The
      development of such cells can be classified into four stages: (1) a prenatal
      period from day 19.5 of gestation extending to 0.5 days after birth; (2) 1 day to
      2 weeks after birth; (3) 2 to 4 weeks after birth; and (4) the final period from
      4 to 8 weeks after birth. Glycoconjugate-producing cells reached maturity by 4
      weeks after birth. Our results indicated that glycoconjugate-producing cells were
      cells along the wall of foveolar lumen, but not those covering the gastric mucosa
      surface. Our results also suggested that the trans to transmost Golgi apparatus
      lamellae were the sites of sulphation in the developing rat stomach.

PMID- 8866647
TI  - The pattern of prothymosin alpha gene expression coincides with that of myc proto
      oncogenes during mouse embryogenesis.
AB  - The nuclear protein prothymosin alpha is thought to play a critical role in
      cellular proliferation. Transcription of the gene encoding prothymosin alpha has
      been shown to be activated by the proto-oncogene c-myc. Also, prothymosin alpha
      mRNA expression correlates with that of c-myc in human colon cancer. We compared
      the previously reported embryonic expression pattern of the proto-oncogene c-myc
      and the pattern of the prothymosin alpha gene by in situ hybridization.
      Prothymosin alpha is transcribed in all tissues expressing c-myc, including brown
      adipose tissue, salivary gland, thymus and liver. In addition, we show that the
      prothymosin alpha gene is active in tissues expressing specifically N-myc such as
      the neuronal anlage and hair follicles in skin. Therefore, during mouse foetal
      development the temporal, spatial and tissue-specific expression patterns of both
      myc proto-oncogenes coincide with the pattern of prothymosin alpha.

PMID- 8866648
TI  - Differential processes of vascular smooth muscle cell differentiation within
      elastic and muscular arteries of rats and rabbits: an immunofluorescence study of
      desmin and vimentin distribution.
AB  - Two main populations of smooth muscle cells exist in the arterial media of adult
      mammals with respect to expression of two intermediate filament proteins:
      vimentin-positive/desmin-negative cells (V+/D-) and vimentin-positive/desmin
      positive ones (V+/D+). However, it is still not understood how this phenotypic
      diversity is established. Since the proportion and the distribution patterns of
      the two muscle cell populations depend both on the type of blood vessel and the
      species examined, the aim of the present study was to determine and to compare
      their developmental origin in various artery segments from two different species.
      Using confocal scanning laser microscopy and sections stained by means of
      immunofluorescence, the distribution patterns of desmin and vimentin were
      compared in transverse sections of thoracic and abdominal aortas (elastic
      arteries) and of the femoral artery (muscular artery) of newborn and adult rats
      (n = 12) and rabbits (n = 12). The comparison of sections labelled with specific
      antibodies showed the existence of a subpopulation of smooth muscle cells in the
      aortas, but not in the femoral artery, which expressed desmin in newborns but not
      in adults. These data suggest that the phenotype of smooth muscle cells in
      elastic arteries but not in muscular arteries is modulated during development.

PMID- 8866649
TI  - Immunohistochemical localization and quantitative analysis of cellular
      glutathione peroxidase in foetal and neonatal rat tissues: fluorescence
      microscopy image analysis.
AB  - To quantitate the developmental changes in selenium-dependent cellular
      glutathione peroxidase during the perinatal period, tissue sections from foetal
      (day 12 to day 22) and neonatal (day 6) rats were stained immunohistochemically
      using specific polyclonal antiserum. The intensity of the staining was quantified
      by fluorescence microscopy image analysis. There was a general trend of enriched
      glutathione peroxidase in the epithelial linings and metabolically active sites.
      Significant fluorescence was detected in cardiomyocytes, hepatocytes, renal
      tubular epithelium, bronchiolar epithelium and intestinal epithelium at day 15.
      The intensity increased in a stepwise manner thereafter. The overall increase in
      the intensity of staining in the heart, liver, kidneys, lungs and intestine was
      1.5-, 2.3-, 1.6-, 1.7- and 3.0-fold, respectively. The phase of most rapid
      increase occurred during the foetal period in the liver, intestine and heart. In
      the kidneys and lungs, glutathione peroxidase increased significantly during
      foetal life, and to a similar extent postnatally. These results suggest that the
      intracellular H2O2-scavenging system develops during the foetal period as an
      essential mechanism for living under atmospheric oxygen conditions. The late
      development observed in the kidneys and lungs is consistent with the relative
      biological immaturity of these organs in full-term neonates.

PMID- 8866650
TI  - Immunohistochemical studies of human tissues with antibody to factor Xa.
AB  - Factor Xa is a serine proteinase which functions principally at coagulation
      cascades. Factor Xa-like immunoreactivity has been examined in several human
      organs. Antibodies to the Factor stained macrophages in some tissues examined,
      including microglia in the brain white matter. They also stained epithelial cells
      in the nose, bronchus and duodenum. Some brainstem neurons, such as those in the
      oculomotor nucleus, substantia nigra and pontine nucleus, were also positive for
      the Factor. As reported by others, these results suggest that factor Xa may have
      pleiotrophic functions. Furthermore, the prefential localization to epithelium in
      the nose and bronchus is interesting in view of the previous notion that several
      viruses targeting the respiratory tract require factor Xa-like cellular
      proteinases for their replication and spread.

PMID- 8866651
TI  - Drug targeting in cancer therapy: the magic bullet, what next?

PMID- 8866652
TI  - Polyethylene glycol modification: relevance of improved methodology to tumour
      targeting.
AB  - Of all the polymers applied to molecule altering structural chemistry,
      polyethylene glycol (PEG) modification has numerous benefits and relatively few
      drawbacks. PEG is now increasingly being applied to the problems of tumour
      targeting, both in the context of the passive targeting of PEG-liposomes and in
      active targeting strategies using PEGylated anti-tumour antibodies. PEG can also
      serve as a useful linker molecule between targeting moieties and other agents,
      including cytotoxic or imaging agents and targeted liposomes. Despite these
      demonstrated benefits and the level of attention which PEGylation has received,
      relatively little consideration has been given to two key areas: first, the
      extent to which the coupling method has an impact on both the functionality of
      the PEG-adduct and the acquisition of beneficial properties; second, that the
      impact of PEGylation on biodistribution is complex, thus any attempt to optimise
      a PEG-peptide or PEG-liposome for a particular task must involve an examination
      of all the individual facets of the effects of PEGylation. Studies investigating
      the underlying principles of tumour targeting suggest that current views
      concerning the optimisation of PEGylated vehicles for tumour localisation need to
      be re-examined.

PMID- 8866653
TI  - Intra-hepatic arterial drug delivery.
AB  - In this review, the pharmacokinetic rationale for hepatic arterial drug therapy
      is discussed, along with techniques that have been developed in order to try to
      enhance the regional advantage accrued from this route of administration.
      Clinical trials of hepatic arterial therapy in patients with primary
      hepatocellular carcinoma and with liver metastases from colorectal carcinoma are
      discussed. Although clinical response rates are significantly better with
      regional as compared with systemic therapy, survival is not prolonged. This is
      mainly due to the development of extrahepatic metastases. A treatment strategy
      using high dose hepatic arterial 5-fluorouracil (5-FU) infusion with the
      deliberate aim of achieving maximum tolerated systemic drug levels has entered
      phase III clinical trial. Monitoring of in vivo tumour pharmacokinetics using 19F
      magnetic resonance spectroscopy and 18F-5-FU positron emission tomography (PET)
      demonstrate elegantly how target drug uptake may be assessed. We plan to use PET
      to monitor intra-tumoral viral transduction and 5-flucytosine conversion rates to
      active 5-FU in our hepatic arterial pro-drug gene therapy programme soon to enter
      clinical trial.

PMID- 8866654
TI  - Regulated expression of artificial chimeric genes contained in retroviral
      vectors: implications for virus-directed enzyme prodrug therapy (VDEPT) and other
      gene therapy applications.
AB  - Replication-defective retroviral vectors were created that contained chimeric
      genes composed of either the albumin (ALB) or the alpha-fetoprotein (AFP)
      transcriptional regulatory sequences linked to the coding domain of the thymidine
      kinase gene from Varicella zoster virus (VZV TK). These viruses were used to
      infect the human hepatoblastoma cell line, HepG2. Subsequent to infection, the
      infected cells were single-cell cloned. The level of expression of VZV TK from
      the chimeric genes correlated with the level of endogenous expression of ALB or
      AFP in most clones, indicating that the transcription of the chimeric VZV TK gene
      is controlled in a similar manner to the endogenous ALB or AFP genes, and that
      sites of viral integration are less important to overall gene expression. Most
      importantly, as the expression of the endogenous ALB gene was modified, so was
      expression of VZV TK from the ALB/VZV TK chimeric gene. This demonstrates that
      retroviruses can deliver a chimeric gene containing tissue-specific
      transcriptional regulatory sequences that can respond to endogenous cell
      regulatory signals resulting in regulated gene expression.

PMID- 8866655
TI  - HPMA copolymer-anticancer drug-OV-TL16 antibody conjugates. 1. influence of the
      method of synthesis on the binding affinity to OVCAR-3 ovarian carcinoma cells in
      vitro.
AB  - The influence of different methods of binding the OV-TL16 antibody and its Fab'
      fragment to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer--drug (adriamycin
      [ADR] or meso chlorin e6 mono(N-2-aminoethylamide) (Mce6)) conjugates on the
      affinity of conjugates to an ovarian carcinoma (OVCAR-3) cell associated antigen
      was investigated. The binding of the antibody to HPMA copolymer--drug (ADR or
      Mce6) conjugates via amino groups resulted in conjugates which were heterogeneous
      in their antigen binding. Coupling, the HPMA copolymer--Mce6 conjugate to the
      carbohydrate region of the antibody resulted in conjugates with a more
      homogeneous distribution of affinity constants than conjugates prepared by
      linking the antibody to the polymer via amino groups. However, both methods
      resulted in a decrease in the affinity constant compared to the native antibody.
      Conjugates prepared with the Fab' frgment of the OV-TL16 antibody demonstrated a
      more homogenous affinity than either conjugate prepared with the whole antibody.
      To verify the hypothesis that the changes in the binding affinity and homogeneity
      are a consequence of conformational changes in the antibody structure, a series
      of physiocochemical methods were employed to characterize the conjugates. The
      excitation energy transfer between OV-TL16 antibody and drugs (ADR and Mce6) and
      the spectral properties of Mce6 were used to monitor the interactions between the
      antibody and drugs. The quenching of the intrinsic fluorescence of the antibody
      was also employed to study its conformational changes. An attempt has been made
      to correlate the biorecognition at the cellular surface with the interactions of
      drug with the antibody molecule and with the changes in antibody conformation.

PMID- 8866656
TI  - Gamma scintigraphy of the biodistribution of 123I-labelled N-(2
      hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates in mice with
      transplanted melanoma and mammary carcinoma.
AB  - An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin conjugate is
      currently under clinical evaluation as a new antitumour agent. It has been shown
      previously that such conjugates exhibit selective tumour accumulation. In this
      study HPMA copolymer doxorubicin conjugates of low (LMW) or high (HMW) molecular
      weight were synthesised (which had a weight average molecular weight (Mw) of
      25,000 and 94,000 respectively) and additionally contained a small amount (1
      mol%) of the comonomer methacryloyltyrosinamide to permit labelling with [123I or
      125I]iodide. Gamma camera imaging using the 123I-labelled probes was used to
      follow time-dependent biodistribution after intraperitoneal (i.p.) or intravenous
      (i.v.) administration to mice bearing subcutaneously either B16F10 melanoma or a
      mammary carcinoma. Imaging showed more rapid clearance of LMW conjugate from the
      peritoneal cavity than HMW conjugate. The images of mice given the LMW conjugate
      revealed rapid urinary excretion of radioactivity after both i.p. and i.v.
      injection with an early high concentration of tracer in the bladder, and
      subsequently a very high concentration in the kidneys, which came to dominate the
      views. Dissection analysis 2 days after administration of the LMW conjugate
      revealed a kidney level of radioactivity corresponding to 25-40% dose/g tissue in
      mice bearing the two tumour models. Following administration of the HMW conjugate
      kidney accumulation at 2 days was less due to retention of the higher molecular
      weight polymer molecules in the circulation, and spleen and liver displayed the
      highest concentrations of radioactivity. The tumour accumulation of LMW and HMW
      conjugates was; mammary carcinoma 3.18 and 5.29% dose/g respectively; B16F10
      melanoma 3.23 and 8.82 %dose/g although these levels of tracer enabled
      visualisation in the images of the mammary carcinoma with HMW conjugate at later
      time points. The smaller size of the B16F10 tumour masses did not permit clear
      visualisation.

PMID- 8866658
TI  - Liposome longevity and stability in circulation: effects on the in vivo delivery
      to tumors and therapeutic efficacy of encapsulated anthracyclines.
AB  - The effect of liposome composition on drug delivery to tumors and therapeutic
      efficacy of liposome-encapsulated anthracyclines was investigated in two murine
      tumor models: an ascitic tumor (J6456 lymphoma) and a solid carcinoma (M-109).
      Longevity in circulation correlated positively with high drug levels in the
      extracellular (ascitic) tumor fluid and with delayed peak tumor levels. Using
      polyethylene-glycol(PEG)-coated liposomes, liposome stability (drug retention)
      was found to be an important determinant of therapeutic efficacy, as indicated by
      the superior survival conferred by high Tm phosphatidylcholines (hydrogenated,
      dipalmitoyl) over low Tm (egg phosphatidyl-choline). Replacing PEG with another
      negatively-charged surface headgroup (phosphatidyl-glycerol, phosphatidyl
      inositol) resulted in relatively shorter longevity in circulation of the liposome
      associated drug, but no detectable differences in anti-tumor efficacy. When
      neither the surface charged headgroup nor the PEG coating are present, the
      resulting drug formulation was significantly less effective than PEG and
      phosphatidylinositol-based formulations in both tumor models. In conclusion,
      longevity in circulation, as obtained with PEG coating, tends to improve the
      therapeutic efficacy of liposome-encapsulated anthracyclines. The current
      therapeutic models were however unable to detect differences between the
      therapeutic activity of PEG and other liposome formulations with relatively small
      differences in circulation longevity.

PMID- 8866657
TI  - Gamma scintigraphy of a 123I-labelled N-(2-hydroxypropyl)methacrylamide copolymer
      doxorubicin conjugate containing galactosamine following intravenous
      administration to nude mice bearing hepatic human colon carcinoma.
AB  - Polymer drug conjugates composed of N-(2-Hydroxypropyl)methacrylamide (HPMA)
      copolymer covalently bound doxorubicin, and containing additionally galactosamine
      to facilitate hepatocyte-specific targeting (HPMA copolymer-dox-gal), were
      synthesised to contain a small amount (approximately 1 mol%) of the monomer
      methacryloyltyrosinamide to permit radioiodination with [123I]iodide. After
      intravenous administration to both normal mice and nude mice bearing hepatic
      human colon carcinoma, the biodistribution of the conjugate was monitored using
      the gamma camera, and also by dissection analysis. Efficient liver accumulation
      of HPMA copolymer-dox-gal was seen in the gamma camera images within 20 min, both
      in normal and tumour-bearing animals. Quantitatively liver uptake was
      approximately 40% dose administered/g liver. Images of the tumour-bearing animals
      showed clearly a much lower accumulation of HPMA copolymer-dox-gal in the colon
      carcinoma deposits within the liver (3-9% dose/g tumour), and this lack of uptake
      was verified by ex vivo imaging of the tumour-containing liver and also by
      dissection analysis. It can be concluded that 123I-labelled HPMA copolymer
      conjugates offer great potential as effective imaging agents and can be used for
      future non-invasive clinical studies. This nuclear imaging method will enable
      optimisation of the dosing schedule by identification of doses of HPMA copolymer
      dox-gal that display receptor saturation (and hence diminished targeting
      efficiency). In addition this conjugate can provide negative images of liver
      associated tumour deposits that do not express the asialoglycoprotein receptor.

PMID- 8866659
TI  - The activity of doxorubicin niosomes against an ovarian cancer cell line and
      three in vivo mouse tumour models.
AB  - Demonstration of the improved doxorubicin pharmacokinetics and tumoricidal
      activity, after a single intravenous dose of 10mg kg-1 doxorubicin sorbitan
      monostearate (Span 60) based niosomes in the mouse adenocarcinoma (MAC) tumour
      model (Uchegbu et al., 1995) preceded the present study in which the activity of
      doxorubicin C16G2 (a hexadecyl diglycerol ether) based niosomes was evaluated
      against naive and established MAC tumour models. C16G2 niosomes were equiactive
      with doxorubicin solution. It is concluded that while in some tumour models,
      niosomal formulations demonstrate some advantages over the free drug, caution is
      advocated in the extrapolation of these results. The activity of doxorubicin
      C16G2 and Span 60 niosomes was also studied against a human ovarian cancer cell
      line and its doxorubicin resistant subline. There was a slight reduction in the
      IC50 against the resistant cell line when the drug was encapsulated in Span 60
      niosomes in comparison to the drug in solution. Taking into account the in-vitro
      release characteristics of the various niosomal formulations, it is concluded
      that the use of niosomal formulations against multidrug resistance shows
      sufficiently encouraging results to warrant further study.

PMID- 8866660
TI  - Resistance to inhibitors of S-adenosyl-L-homocysteine hydrolase in C1300 murine
      neuroblastoma tumor cells is associated with increased methionine
      adenosyltransferase activity.
AB  - Adaptive changes occurring in C1300 murine neuroblastoma cell lines developed for
      resistance to nucleoside analogue inhibitors of S-adenosyl-L-homocysteine
      hydrolase (AdoHcyase, EC 3.3.1.1) were investigated. Two drug-resistant cell
      lines, rMNB-MDL-7-2 and rMNB-Deaz-7-2, were established from wild-type C1300
      neuroblastoma cells (wMNB) following incubation with the AdoHcyase inhibitors (Z)
      4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (MDL 28,842) and 3-deazaneplanocin A,
      respectively. The nucleoside analogue concentration required to inhibit cellular
      proliferation by 50% (IC50) was 3.2 x 10(2) to 4.3 x 10(3) fold higher in the
      resistant cells when compared with the wMNB cell line. The proliferation rates of
      the resistant cell lines under in vitro or in vivo conditions were significantly
      lower than the wMNB cell line. In contrast to wMNB, both resistant cell lines had
      slower doubling times in tissue culture (22% longer) and smaller tumor weights
      (55% smaller) 14 days after implantation in A/J mice. No significant differences
      in AdoHcyase activity were noted between the resistant and wild-type cell lines.
      The resistant cell lines had concentrations of S-adenosyl-L-methionine that were
      five times higher and methionine adenosyltransferase (MAT, EC 2.5.1.6) activities
      that were two to four times greater than the wMNB phenotype. These data indicate
      that neuroblastoma tumor cell resistance to AdoHcyase inhibitors is associated
      with an adaptive increase in MAT activity. This cellular response facilitates
      methylation by elevating intracellular concentrations of the methyl donor S
      adenosyl-L-methionine, thereby sustaining tumor cell viability in the presence of
      MDL 28,842 and 3-deazaneplanocin A.

PMID- 8866661
TI  - Establishment and characterization of four human medulloblastoma-derived cell
      lines.
AB  - We have established four cell lines, UW228-1, UW228-2, UW228-3 and UW443, from
      two posterior fossa medulloblastomas. The three UW228 sublines originated from a
      tumor with a diploid DNA content, while the tumor of origin of UW443 was
      predominantly tetraploid. Both tumors displayed areas of immunopositivity for
      synaptophysin and glial fibrillary acidic protein. All four cell lines have been
      grown as monolayers in continuous culture for 50 to 200 passages, are not contact
      inhibited at high density, and form colonies in soft agar. The UW228 sublines are
      aneuploid, have similar modal chromosome numbers, similar chromosomal
      duplications and identical marker chromosomes, and display loss of heterozygosity
      for identical sequences at the distal end of chromosome 17p. UW443 is diploid and
      also shows loss of heterozygosity for a distal sequence on chromosome 17p. All
      lines are immunopositive for two or more neurofilament proteins, three lines
      (UW228-1, UW228-2 and UW443) are immunopositive for synaptophysin, and none are
      immunopositive for glial fibrillary acidic protein. The lines differ in
      sensitivity to the alkylating agents 1,3-bis(2-chloroethyl)-1-nitrosourea and N
      methyl-N'-nitro-N-nitrosoguanidine. They also differ in dependence on the DNA
      repair protein O6-methylguanine-DNA methyltransferase for alkylating agent
      resistance and in levels of the DNA repair activities apurinic/apyrimidinic
      endonuclease and DNA polymerase beta. These properties establish UW228-1, UW228
      2, UW228-3 and UW443 as four new, phenotypically distinct medulloblastoma-derived
      cell lines.

PMID- 8866662
TI  - mRNA levels and enzyme activities of protein phosphatases in drug-resistant rat
      ascites hepatomas.
AB  - mRNA levels and enzyme activities of the serine/threonine protein phosphatases
      (EC 3.1.3.16) type 1 (PP1) and 2A (PP2A) in drug-resistant rat ascites hepatoma
      cells were examined and compared with those in the parental drug-sensitive cell
      lines, under drug-free conditions. The mRNA levels of PP1 alpha were much higher
      in all the hepatomas, either sensitive or resistant, compared with normal liver.
      The mRNA level of PP2C alpha was decreased in the drug-resistant hepatomas
      compared with the parental drug-sensitive hepatomas, whereas mRNA levels of PP1
      alpha, PP1 gamma 1 and PP2A alpha in resistant hepatomas showed diverse
      deviations, which are not drug-resistance-specific. However, both spontaneous and
      potential PP1 activities in particulate fractions of the resistant hepatomas were
      markedly increased compared with those of the sensitive hepatomas and normal rat
      liver. Western blot analysis showed that the resistant hepatomas contained larger
      amounts of PP1 alpha in both cytosolic and particulate fractions than the
      sensitive hepatomas and rat liver. In both groups of hepatomas, spontaneous and
      potential activities of PP2A were kept lower than those in normal rat liver, but
      there was no difference between drug-sensitive and -resistant hepatomas. These
      results suggest an involvement of PP1 in development of drug-resistant phenotype.

PMID- 8866663
TI  - Novel substrate analogs delineate an endocytotic mechanism for uptake of folate
      via the high-affinity, glycosylphosphatidylinositol-linked transport protein in
      L1210 mouse leukemia cells.
AB  - The mechanism of folate uptake, mediated by the high-affinity folate receptor
      linked via glycosylphosphatidylinositol to the plasma membrane of L1210 mouse
      leukemia cells, has been investigated with the use of two substrate analogs, a
      fluorescein derivative of folate and a gold-conjugated, streptavidin-biotin
      derivative of folate, in conjunction with fluorescence microscopy and electron
      microscopy. These substrate probes bind to receptors that are uniformly
      distributed rather than clustered on the membrane, and the receptor-probe
      complexes are internalized by an endocytotic mechanism in which vesicles
      containing the complexes migrate from the membrane toward the nucleus.
      Measurements using [3H]-folate demonstrate that receptors are recycled to the
      plasma membrane.

PMID- 8866665
TI  - KRN7000, a novel immunomodulator, and its antitumor activities.
AB  - KRN7000, a compound with a novel alpha-galactosylceramide structure, showed
      potent tumor growth inhibitory activities in B16-bearing mice and markedly
      stimulated lymphocytic proliferation in allogeneic mixed leukocyte reaction,
      suggesting that KRN7000 is a biological response modifier. To confirm this
      suggestion, we examined the abilities of KRN7000 to enhance in vitro and in vivo
      natural killer (NK) activities, and found that KRN7000 enhanced in vitro and in
      vivo NK activities, and its potency on in vivo NK activity was much stronger than
      those of Poly I:C, which is a positive control, or the representative BRMs OK432
      and Lentinan. In addition, since spleen cells intravenously treated with KRN7000
      also showed potent cytotoxic activities against B16 and EL-4 cells, we evaluated
      the capability of KRN7000 to prolong the survival period of mice intravenously
      inoculated with B16 cells or mice intraperitoneally inoculated with EL-4 cells.
      In these models, KRN7000 (100 micrograms/kg) significantly prolonged the lifespan
      of mice, and its potency was stronger than that of Mitomycin C, a typical
      chemotherapeutic agent, in two models. These results demonstrate that KRN7000
      would be a useful agent for cancer therapy.

PMID- 8866664
TI  - Novel mechanism of resistance to paclitaxel (Taxol) in human K562 leukemia cells
      by combined selection with PSC 833.
AB  - A paclitaxel-resistant cell line, KPTA5, was established by co-selecting the
      parental erythroleukemic cell line K562 with stepwise increased concentrations of
      paclitaxel (Taxol) in the presence of the cyclosporin D analogue PSC 833 (2
      microM), a potent modulator of the multidrug resistance phenotype. KPTA5 cells
      are 9-fold resistant to paclitaxel and taxotere, but do not exhibit significant
      resistance to Vinca alkaloids, etoposide, anthracyclines, antimetabolites, or
      alkylating agents. Doubling time and morphology were similar to the parental K562
      cells. Reverse transcriptase-polymerase chain reaction (rt-PCR) analysis revealed
      no alterations in the expression of the mdr1 and MRP genes. Cellular paclitaxel
      accumulation was unchanged. Cell cycle analyses showed that at 20 nM there was a
      significantly higher proportion of K562 cells blocked in G2/M, in comparison with
      KPTA5 cells. In both cases, disruption of the mitotic spindles and the presence
      of multiple mitotic asters were comparable but occurred at lower paclitaxel
      concentrations in K562 cells than in KPTA5 cells. There was no difference in
      total tubulin content between K562 and KPTA5 cells as analyzed by immunoblotting
      with an anti-beta-tubulin monoclonal antibody. However, we found that KPTA5 cells
      presented a 2-fold increase both in 5 beta-tubulin mRNA expression and in the
      corresponding tubulin protein Class IV isotype content, as evaluated by rt-PCR
      and immunostaining. In conclusion, the KPTA5 cell line displays a novel mechanism
      of resistance to paclitaxel which does not involve altered cellular drug
      accumulation. The data presented suggest that alterations in expression of the 5
      beta-tubulin gene may be involved in paclitaxel resistance.

PMID- 8866666
TI  - Evolution of drug resistance in CCRF-CEM human leukemia cells selected by
      intermittent methotrexate exposure.
AB  - A clinically relevant mechanism of acquired methotrexate (MTX) resistance is
      decreased MTX polyglutamate (MTXGn) synthesis (McCloskey et al. J. Biol. Chem.
      266:6181, 1991) secondary to deficient folylpolyglutamate synthetase (FPGS)
      activity. Earlier studies showed that this mechanism resulted after intermittent
      MTX treatment, but did not define its evolution in populations or its clonal
      frequency of occurrence and heterogeneity. We thus studied evolution of
      resistance in CCRF-CEM human leukemia cell populations and clones after repeated
      treatment with 30 microM MTX for 24 h. In populations, MTX resistance was
      detectable after 1 treatment and increased in degree as total cycles increased to
      7. Defective MTXGn synthesis in populations was the only resistance mechanism
      detected, and FPGS activity in extracts decreased with treatment cycle. After 1
      treatment, defective MTXGn synthesis was the major (27/48 clones) form of
      resistance; 18 clones were sensitive, while 1 clone with a DHFR-related change,
      no clones with decreased MTX uptake, and 2 complex phenotypes were observed.
      Sporadic clones with DHFR-mediated resistance appeared up to cycle 4, but
      defective MTXGn synthesis remained the major resistance mechanism. The degree of
      clonal resistance tended to increase with treatment cycle, but 1 clone in cycle 2
      was similar to the clones from cycle 7. No change in FPGS gene copy number or
      restriction pattern, or FPGS mRNA level or size (2.3 Kb) was detected in
      populations. Decreased FPGS activity must result from decreased translation,
      increased protein turnover, or a point mutation affecting catalysis.

PMID- 8866667
TI  - Variants of the human prostate LNCaP cell line as tools to study discrete
      components of the androgen-mediated proliferative response.
AB  - Androgens regulate the proliferation of their target cells through a sequential
      two-step mechanism. In the first step, androgens increase proliferation rates;
      following this proliferative response, a second step of proliferative shutoff
      ensues. Human prostate LNCaP cell variants were used to assess whether the
      proliferative and shutoff effects of androgens could be segregated selectively by
      manipulating the hormonal milieu. The LNCaP-FGC and LNCaP-LNO cell lines were
      derived from the same biopsy specimen but exhibited different proliferative
      responses. Cell proliferation was inhibited by treatment with 10% charcoal
      dextran stripped human serum in the LNCaP-FGC variant but not in LNCaP-LNO cells.
      Physiological androgen concentrations induced a proliferative shutoff in LNCaP
      LNO cells (G1 arrest), an effect also expressed by LNCaP-FGC cells. This G1
      arrest was irreversible in the LNCaP-FGC variant but was reversed upon androgen
      withdrawal in LNCaP-LNO cells. A new variant (LNCaP-TJA) was selected from LNCaP
      LNO cells treated with 30 nM methyltrienolone for 4 months; these cells
      proliferated maximally regardless of the presence of androgens. All three cell
      variants had functional androgen receptors, and androgens induced prostate
      specific antigen secretion. The androgen-induced proliferative shutoff in LNCaP
      FGC and LNO cells was partially antagonized by antiandrogens and was not mediated
      by autocrine factors. Finally, the variant LNCaP cell lines described herein are
      probably representative of phenotypes present in prostate cancer patients during
      the course of this disease and may arise from selective pressure imposed by
      therapeutic protocols aimed at modifying the hormonal milieu of the host.

PMID- 8866669
TI  - Reference listings in cancer research.

PMID- 8866668
TI  - TNF-induced apoptosis in multidrug resistant friend erythroleukemia is not
      influenced by the P-glycoprotein and glutathione status of the cell line.
AB  - The effects that TNF-alpha exerts on Friend erythroleukemia (FLC) and on one
      multidrug resistant variant (FLC-DXR) of the cell line were studied. Resistance
      to doxorubicin of FLC-DXR entails two mechanisms: overexpression of P
      glycoprotein; and increased glutathione-related activities. Both these might also
      decrease the effects of the cytokine. Nonetheless, TNF caused even greater
      cytotoxicity and apoptosis, with no induction of differentiation markers, in FLC
      DXR. In addition, TNF produced minor changes of the levels of reduced and
      oxidized glutathione in the cell lines, and its cytotoxic effects were not
      inluenced by agents that modify the cell glutathione content such as buthionine
      sulfoximine, ethacrynic acid, or N-acetyl cysteine. We can exclude that the
      mechanisms of drug resistance of FLC-DXR prevent the response to the cytokine.

PMID- 8866670
TI  - Which brain regions are critically involved in the retrieval of old episodic
      memory?
AB  - Memory is two-sided like the head of Janus: it looks into the past (retrograde
      memory) and the future (anterograde memory). While current opinion assumes a
      strong anatomical interdigitation in the processing of either kind of memory,
      recent single case reports and results obtained with the positron emission
      tomographic subtraction method indicate the likely existence of a dissociation:
      regions of the limbic system are primarily engaged in the encoding of
      autobiographical and semantic information, while cortical areas in the
      orbitofrontal and anterolateral temporo-polar regions are principally engaged in
      information retrieval. Within this retrieval system the right hemisphere may
      subserve episodic memory retrieval, and the left retrieval from the knowledge
      system (semantic memory).

PMID- 8866671
TI  - The failure of current immunotherapy for malignant glioma. Tumor-derived TGF
      beta, T-cell apoptosis, and the immune privilege of the brain.
AB  - Human malignant gliomas are rather resistant to all current therapeutic
      approaches including surgery, radiotherapy and chemotherapy as well as antibody
      guided or cellular immunotherapy. The immunotherapy of malignant glioma has
      attracted interest because of the immunosuppressed state of malignant glioma
      patients which resides mainly in the T-cell compartment. This T-cell suppression
      has been attributed to the release by the glioma cells of immunosuppressive
      factors like transforming growth factor-beta (TGF-beta) and prostaglandins. TGF
      beta has multiple effects in the immune system, most of which are inhibitory. TGF
      beta appears to control downstream elements of various cellular activation
      cascades and regulates the expression of genes that are essential for cell cycle
      progression and mitosis. Since TGF-beta-mediated growth arrest of T-cell lines
      results in their apoptosis in vitro, glioma-derived TGF-beta may prevent immune
      mediated glioma cell elimination by inducing apoptosis of tumor-infiltrating
      lymphocytes in vivo. T-cell apoptosis in the brain may be augmented by the
      absence of professional antigen-presenting cells and of appropriate costimulating
      signals. Numerous in vitro studies predict that tumor-derived TGF-beta will
      incapacitate in vitro-expanded and locally administered lymphokine-activated
      killer cells (LAK-cells) or tumor-infiltrating lymphocytes. Thus, TGF-beta may be
      partly responsible for the failure of current adoptive cellular immunotherapy of
      malignant glioma. Recent experimental in vivo studies on non-glial tumors have
      corroborated that neutralization of tumor-derived TGF-beta activity may
      facilitate immune-mediated tumor rejection. Current efforts to improve the
      efficacy of immunotherapy for malignant glioma include various strategies to
      enhance the immunogenicity of glioma cells and the cytotoxic activity of immune
      effector cells, e.g., by cytokine gene transfer. Future strategies of cellular
      immunotherapy for malignant glioma will have to focus on rendering glioma cell
      targeting immune cells resistent to local inactivation and apoptosis which may be
      induced by TGF-beta and other immunosuppressive molecules at the site of
      neoplastic growth. Cytotoxic effectors targeting Fas/APO-1, the receptor protein
      for perforin-independent cytotoxic T-cell killing, might be promising, since
      Fas/APO-1 is expressed by glioma cells but not by untransformed brain cells, and
      since Fas/APO-1-mediated killing in vitro is not inhibited by TGF-beta.

PMID- 8866672
TI  - Plasmalogens, phospholipases A2 and signal transduction.
AB  - Several lines of evidence indicate that the breakdown of plasmalogens in neural
      membranes during neurodegenerative diseases is a receptor-mediated process
      catalyzed by a plasmalogen-selective phospholipase A2. This enzyme has recently
      been purified from bovine brain. It does not require Ca2+ and is localized in
      cytosol. It has a molecular mass of 39 kDa and is strongly inhibited by
      glycosaminoglycans, with the pattern of inhibition being heparan sulfate >
      hyaluronic acid > chondroitin sulfate > heparin. This plasmalogen-selective
      phospholipase A2 is also inhibited by gangliosides and sialoglycoproteins.
      Substrate specificity and the effects of metal ions, detergents and inhibitors
      suggest that this phospholipase A2 is different from the well-known 85 kDa Ca(2+)
      dependent cytosolic phospholipase A2 that has recently been cloned and is not
      plasmalogen-selective. The plasmalogen-selective phospholipase A2 may be
      regulated by glycosaminoglycans and sialoglycoconjugates and may be involved in
      the regulation of K+ channels. This enzyme, which plays a major role in the
      release of fatty acids during ischemic injury and reperfusion, shows promise as a
      major target for drug therapy.

PMID- 8866673
TI  - Regulation of masculine sexual behavior: involvement of brain opioids and
      dopamine.
AB  - In recent years much has become known about the substrates in the brain involved
      in the regulation of masculine sexual behavior and the involvement of specific
      neurochemicals in these brain areas. In the present paper the experimental data
      concerning the involvement of a number of brain areas in sexual behavior are
      reviewed, in relation to an incentive motivational theory of sexual behavior. The
      review is restricted to the involvement of opioids and dopamine, of which the
      role in sexual motivation and behavior is best documented. Opioids in the medial
      preoptic area (mPOA) impair sexual performance, although the endogenous opioids
      systems may be quiescent in normal, sexually active rats. Dopamine in the mPOA
      has a facilitative role in the masculine sexual performance. The corticomedial
      amygdala is involved in processing of sensory information, especially olfactory
      stimuli, which are subsequently directed towards the mPOA. Local beta-endorphin
      infusion interferes with this processing. Endogenous opioids in the ventral
      tegmental area activate the mesoaccumbens dopamine system and stimulate the
      sexual motivation. Increased dopamine transmission in the nucleus accumbens
      correlates with increased sexual motivation and vice versa. The basolateral
      amygdala plays an essential role in the association of environmental stimuli with
      reward and therefore in the expression of conditioned sexual motivation. Finally,
      the reviewed data are integrated and a comprehensive view on the relations
      between various neural substrates is composed.

PMID- 8866674
TI  - Retrograde messengers, long-term potentiation and memory.
AB  - Long-term potentiation has been involved in certain forms of learning and memory.
      In the CA1 region of the hippocampus, long-term potentiation (LTP) is triggered
      postsinaptically and, at least in part, it expression depends on presynaptic
      mechanisms. Therefore, a retrograde messenger that is released from the
      postsynaptic dendrite and diffuses back across the synapse to increase
      neurotransmitter release has been proposed. Several candidates including lipid
      mediators such as arachidonic acid and platelet-activating factor, and gases such
      as nitric oxide and carbon monoxide, have recently attracted much interest. The
      involvement of these intercellular messengers in LTP, the relation between LTP
      and memory and the role of these candidate retrograde messengers in the
      acquisition and consolidation of memories are discussed. Evidence for the
      involvement of NO, CO and PAF in the early stages of memory processing will be
      presented.

PMID- 8866675
TI  - The inflammatory response system of brain: implications for therapy of Alzheimer
      and other neurodegenerative diseases.
AB  - Cultured brain cells are capable of generating many molecules associated with
      inflammatory and immune functions. They constitute the endogenous immune response
      system of brain. They include complement proteins and their regulators,
      inflammatory cytokines, acute phase reactants and many proteases and protease
      inhibitors. Most of the proteins are made by microglia and astrocytes, but even
      neurons are producers. Many appear in association with Alzheimer disease lesions,
      indicating a state of chronic inflammation in Alzheimer disease brain. Such a
      state can apparently exist without stimulation by peripheral inflammatory
      mediators or the peripheral immune system. A strong inflammatory response may be
      autotoxic to neurons, exacerbating the fundamental pathology in Alzheimer disease
      and perhaps other neurological disorders. Autotoxic processes may contribute to
      cellular death in chronic inflammatory diseases affecting other parts of the
      body, suggesting the general therapeutic value of anti-inflammatory agents. With
      respect to Alzheimer disease, multiple epidemiological studies indicate that
      patients taking anti-inflammatory drugs or suffering from conditions in which
      such drugs are routinely used, have a decreased risk of developing Alzheimer
      disease. In one very preliminary clinical trial, the anti-inflammatory drug
      indomethacin arrested progress of the disease. New agents directed against the
      inflammatory processes revealed in studies of Alzheimer disease lesions may have
      broad therapeutic applications.

PMID- 8866676
TI  - Comparative study of aprosody in Alzheimer's disease and in multi-infarct
      dementia.
AB  - Prosody is defined as the melodic line of language. In this study we included 25
      patients with probable Alzheimer's disease and 14 with multi-infarct dementia for
      a comparative cross-sectional study of prosody. Neuropsychological analysis was
      based on Mini-Mental test, Blessed Scale and Clinical Dementia Rating. We used
      the criteria of Monrad-Krohn to evaluate prosodic categories. We found intrinsic
      aprosody in 8 patients with Alzheimer's disease and in none of the patients with
      multi-infarct dementia (prevalence ratio: 1.82, 95% CI: 1.32-2.51), and emotional
      aprosody in 17 patients with Alzheimer's disease in comparison to 4 with multi
      infarct dementia (prevalence ratio: 1.8, 95% CI: 1.04-3.18). The differences in
      intellectual and inarticulate aprosody were not significant. We conclude that
      aprosody is more frequent and severe in Alzheimer's disease than in multi-infarct
      dementia.

PMID- 8866677
TI  - Pattern visual evoked potential mapping in Alzheimer's disease: correlations with
      visuospatial impairment.
AB  - We evaluated pattern visual evoked potentials (PVEPs) in patients with
      Alzheimer's disease (AD) and correlated the neurophysiological results with
      visuospatial performances in order to understand better the underlying causes of
      visual disturbances. Latencies and topographical distribution of PVEP components
      were evaluated in 20 AD patients who underwent an extensive battery of
      neuropsychological tests. Mean latencies of N70 and P100 were normal in AD
      patients, while mean latencies of N140 and P200 were significantly increased in
      comparison with age-matched healthy controls. The topographical distribution of
      PVEP components did not show any significant difference between the two groups.
      Visuospatial impairment was detected in 8 patients (40%). Statistically
      significant positive correlations were observed between P200 amplitude (posterior
      right hemisphere mean z score) and performance in visuospatial tests. Our data
      are consistent with a sparing of foveal retinocortical pathways and with the
      selective dysfunction of either corticocortical connections between the striate
      cortex and the visual associative structures or of right temporo-parieto
      occipital visual analyzers.

PMID- 8866678
TI  - Cognition-related EEG abnormalities in nondemented Down syndrome subjects.
AB  - Down syndrome (DS) subjects develop Alzheimer disease (AD) histopathology before
      they develop dementia. We compared the resting and flash stimulated
      electroencephalogram (EEG) of nondemented adult DS and age-matched control
      subjects, in search of EEG abnormalities that might correlate with AD
      histopathology. DS subjects had increased absolute power in all the EEG bands,
      independent of cognition functions measured by the Mini Mental State Examination
      and Picture Absurdities Test scores. In the power spectrum of the resting EEG, we
      found a cognition-related increase in power at 4.5 and 8.8 Hz, indicative of
      alpha-slowing, as in AD patients. In the stimulated EEG, we found several
      cognition-related abnormalities, such as decreased responses to 12-Hz stimulation
      and decreased integral of beta- and gamma-band responses, indicative of decreased
      responsiveness to photic stimulation, as in AD patients. Therefore, nondemented
      DS and AD patients share several cognition related EEG abnormalities which are
      probably due to AD histopathology.

PMID- 8866679
TI  - Hippocampal pathology reflects memory deficit and brain imaging measurements in
      Alzheimer's disease: clinicopathologic correlations using three sets of
      pathologic diagnostic criteria.
AB  - Neurofibrillary tangles (NFT), neuritic plaques and amyloid load were quantified
      in sections of the hippocampus at the level of the lateral geniculate body in 41
      consecutive cases fulfilling pathological criteria for diagnosis of Alzheimer's
      disease (AD) and coming to autopsy after longitudinal study during life. A strong
      correlation was found between NFT density in the hippocampus and cognitive
      impairment scores obtained shortly before death, particularly with scores of
      memory impairment. Weaker and less consistent correlations were found for
      hippocampal neuritic plaques and amyloid load with cognitive/memory deficits. No
      significant correlations were found between hippocampal pathology and either age
      of onset or disease duration. All three measures of hippocampal pathology were
      inversely correlated with the minimum medial temporal lobe (MTL) width, a measure
      of the MTL atrophy made from temporal-lobe-oriented X-ray computed tomography
      scans performed during life; the strongest correlation being between atrophy of
      the MTL and NFT density in the hippocampus.

PMID- 8866680
TI  - Analysis of amyloid precursor protein mRNAs in skin fibroblasts in Down's
      syndrome.
AB  - We examined amyloid precursor protein (APP) mRNAs expression in skin fibroblasts
      from Down's syndrome (DS) patients of different ages to determine the time of
      occurrence of abnormal splicing. The ratio of APP770 + 751 mRNA to APP695 mRNA
      (APP770 + 751/695) was significantly increased in the young DS group and adult DS
      group compared with the age-matched control groups (p < 0.01, p < 0.05), but no
      significant increase was observed in the aged DS group compared with the age
      matched control group. These findings suggest that metabolic abnormalities of the
      APP gene occur at a very early stage of DS, at a mean age of about 5 years.
      Therefore, metabolic abnormalities of the APP gene are considered to appear at a
      very young age also Alzheimer's disease (AD). In this study, we confirmed that
      examination of the APP gene in skin fibroblasts might be useful for early
      diagnosis of AD.

PMID- 8866681
TI  - The spatial pattern of discrete beta-amyloid deposits in Alzheimer's disease
      reflects synaptic disconnection.
AB  - The spatial pattern of discrete beta-amyloid (A beta) deposits was studied in the
      superficial laminae of cortical fields of different types and in the hippocampus
      in 6 cases of Alzheimer's disease (AD). In 41/42 tissues examined, discrete A
      beta deposits were aggregated into clusters and in 34/41 tissues (25/34 of the
      cortical tissues), there was evidence for a regular periodicity of the A beta
      deposit clusters parallel to the tissue boundary. The dimensions of the clusters
      varied from 400 to > 12,800 microns in different tissues. Although the A beta
      deposit clusters were larger than predicted, the regular periodicity suggests
      that they develop in relation to groups of cells associated with specific
      projections. This would be consistent with the hypothesis that the distribution
      of discrete A beta deposits in AD could reflect progressive synaptic
      disconnection along interconnected neuronal pathways. This implies that amyloid
      deposition could be a response to, rather than a cause of, synaptic disconnection
      in AD.

PMID- 8866682
TI  - The role of autoimmunity in vascular dementia.
AB  - It is now known that immunologic mechanisms have a role in the initiation of
      atherosclerotic processes. No antibodies against vascular endothelial cell (VEC)
      specific antigenic systems have been demonstrated in the pathogenesis of small
      vessel (lacunar) infarcts, though autoantibodies have been detected in 80% of
      patients with multi-infarct dementia. We studied VEC-specific antibodies in 17
      patients with a diagnosis of vascular dementia; in 17 nondemented patients with
      small vessel infarcts and in 16 healthy, nondemented control group patients by
      using the Terasaki microtoxicity method. All three groups were correlated
      according to known risk factors. VEC-specific antibodies were positive in 94%
      demented patients, whereas no antibodies were detected in patients with small
      vessel infarcts or in the control group. This result may suggest the existence of
      an immunologic mechanism in the etiopathogenesis of vascular dementia differing
      form small vessel infarcts.

PMID- 8866683
TI  - Alterations in tau protein metabolism during normal aging.
AB  - It is unknown whether aging and Alzheimer's disease (AD) are on the same
      continuum, or whether they are qualitatively distinct. Tau protein has been
      identified as a major constituent of paired helical filaments (PHFs) and AD is
      characterised by a major redistribution of the normal tau protein pool into PHFs.
      Little is known about the changes in tau protein distribution that occur in the
      course of normal aging. We have examined PHF-bound and normal tau fractions in
      frontal, temporal, parietal and occipital neocortex, cerebellum, hippocampus and
      entorhinal cortex in 15 cognitively unimpaired individuals aged 19-88 years at
      death. Insoluble tau protein in the PHF fraction did not increase with aging in
      any brain region, despite the appearance of neurofibrillary pathology at low
      density in the more elderly cases. By contrast, normal tau protein decreased with
      aging (r = 0.32, p < 0.001), with an average loss of 14% of soluble tau per
      decade after the age of 20 years. This was unrelated either to neurofibrillary or
      beta-amyloid pathology. Frontal grey matter and hippocampus were most vulnerable
      to age-related tau loss, decreasing by as much as 90% in the older subgroup.
      These findings contrast with those we have previously reported in AD, where the
      redistribution of tau protein into the PHF-bound fraction was highly correlated
      with the extent of neurofibrillary pathology, and suggest that the mechanisms of
      tau loss in aging and AD are distinct. Age-related tau loss may underlie the
      neuropsychological impairments seen in the non-demented elderly.

PMID- 8866684
TI  - Isolated amnesia with slow onset and stable course, without ensuing dementia: MRI
      and PET data and a six-year neuropsychological follow-up.
AB  - Patient EDS presented with an amnesic disorder of insidious onset (4 years) that
      remained stable and restricted to memory functions over a 10-year course.
      Repeated neuropsychological evaluations over 6 years showed a moderate-to-severe,
      stable impairment of long-term memory and of memory for public events, and a
      milder, stable impairment of autobiographic memory and of short-term memory.
      Language, perception, praxis and 'frontal' functions were fully preserved. MRI
      showed atrophy of the right hippocampus, of the right mammillary body and of the
      sylvian fissure (bilaterally, but more marked on the left). On PET scan,
      metabolic activity in the mesial temporal structures was significantly reduced on
      the right and was at lower normal levels on the left. The disorder observed in
      EDS is similar to that recently reported in other patients. Possible etiologies
      of the selective amnesia observed in EDS are considered and their implications
      discussed.

PMID- 8866685
TI  - Steady-state pharmacokinetics of tacrine in long-term treatment of Alzheimer
      patients.
AB  - The pharmacokinetics of the cholinesterase inhibitor tacrine was studied in 5
      Alzheimer patients during 12-31 months of treatment. A mean average steady-state
      concentration in plasma ranging from 1.1 to 30 ng/ml was obtained with doses
      ranging from 40 to 160 mg of tacrine daily. During treatment with 80 mg daily a
      maximal plasma concentration of tacrine (8.7 +/- 0.6 ng/ml) was obtained 1.3 +/-
      0.2 h after intake of the morning dose. The mean elimination half-life was
      estimated at 5-7 h and remained unchanged when the tacrine dose was increased.
      The plasma concentration of tacrine was stable during long-term treatment with
      tacrine and no tolerance was observed regarding its cholinesterase inhibitory
      effect. A maximal 40% inhibition of plasma cholinesterase (ChE) activity and 60%
      inhibition of acetylcholinesterase activity in red blood cells was measured
      following treatment with the highest dose of 160 mg tacrine daily. A significant
      correlation was obtained between the plasma concentration of tacrine and the
      inhibition of ChE activity (p < 0.001). The tacrine concentration in CSF was
      measured in each patient on 1-3 occasions during the treatment and the ratio
      CSF/plasma concentration was estimated to be 0.47 +/- 0.09 (n = 11).

PMID- 8866686
TI  - Low apolipoprotein E4 allelic frequency in Alzheimer's disease and functional
      psychiatric disorders.

PMID- 8866687
TI  - Apolipoprotein E genotype does not promote the clinical progression of manifest
      Alzheimer's disease.

PMID- 8866688
TI  - The cerebellar model of neural grafting: structural integration and functional
      recovery.
AB  - A synopsis is presented of the recent history of cerebellar tissue
      transplantation over the past 25 years. The properties of growth and
      differentiation of cerebellar grafts placed intraocularly or intracranially are
      reviewed, as well as the interaction of heterotopic and orthotopic grafts with
      the host brain. Particular emphasis is placed on the use of ataxic mouse mutants
      as recipients of donor cerebellar tissue for the correction of their structural
      deficits and the functional recovery of behavioural responses.

PMID- 8866689
TI  - Nerve growth factor modulates information processing in the auditory thalamus.
AB  - The spatio-temporal organization of spike discharges was studied in rat auditory
      thalamus (i.e., medial geniculate body and auditory sector of thalamic reticular
      nucleus) following a 2-week continuous intracerebroventricular administration of
      nerve growth factor (NGF). Recording of extracellular single-unit activity
      indicated that, in medial geniculate body, NGF induced a significant increase of
      the mean firing rate. In thalamic reticular nucleus, where units tend to
      discharge in bursts, NGF increased the average burst size (number of spikes) and
      the intraburst frequency without affecting the firing rate. Following white noise
      acoustical stimulation, in medial geniculate body, more onset excitation and a
      lower signal-to-noise ratio were observed in NGF-treated rats than in controls.
      Conversely, in thalamic reticular nucleus, NGF-treated animals showed more
      inhibitory responses than controls. In addition, within the medial geniculate
      body, functional interactions between pairs of units simultaneously recorded from
      different electrodes were greatly increased by the nerve growth factor treatment.
      These data indicate that modifications of temporal pattern of discharges in
      selected brain regions are among the effects induced by the
      intracerebroventricular administration of nerve growth factor.

PMID- 8866690
TI  - Effects of dietary preference and galanin administration in the paraventricular
      or amygdaloid nucleus on diet self-selection.
AB  - Microinjection of galanin into the paraventricular nucleus (PVN) of the
      hypothalamus has been reported to predominantly increase dietary fat consumption
      during the light or late dark periods. However, there have been no studies of the
      macronutrient-specific effects of galanin administered into the amygdala (AMY).
      We used male Sprague-Dawley rats to test the effect of galanin administered into
      the PVN or central nucleus of the AMY on diet selection using two different
      protocols: the two-choice composite diet (10% or 55% energy as fat) (Study 1) or
      the three-choice macronutrient diet (Study 2). In the first study, total food
      intake was significantly increased 60 min after galanin injection (0.3 nmol) into
      either the PVN or AMY, but there was no difference in intake between the low- and
      high-fat diets. In Study 2, using the three-choice macronutrient diet, the
      feeding stimulation produced by galanin in the PVN also was not diet-dependent.
      In the AMY, there was a significant effect of diet on the feeding response to
      galanin, due primarily to the lack of stimulation of protein intake, whereas the
      intakes of fat and carbohydrate were not significantly different. In summary,
      there was no difference in the effect of galanin on fat versus carbohydrate
      intake for either nuclei, whether animals were injected during the light or the
      late-dark phase. Because rats often display preferences when allowed to choose
      among individual macronutrient sources, we also examined the relationship between
      baseline macronutrient preference and the feeding response to galanin in groups
      of highly fat-preferring and carbohydrate-preferring rats (Study 3). After PVN
      galanin injection, fat-preferring rats demonstrated significant increases in
      their consumption of both carbohydrate and fat, whereas carbohydrate-preferring
      rats responded by eating carbohydrate almost exclusively. There were significant
      positive associations between baseline macronutrient intake and galanin-induced
      intake. The results of these studies combined suggest that the effect of galanin
      on macronutrient selection is not specific for fat and that underlying
      macronutrient preferences are important in determining the feeding response to
      galanin.

PMID- 8866691
TI  - Seizure activity causes elevation of endogenous extracellular kynurenic acid in
      the rat brain.
AB  - This study was designed to examine the effects of several classic convulsants on
      the extracellular concentration of the anticonvulsant and neuroprotective brain
      metabolite kynurenic acid (KYNA) in the rat brain. Drug effects were investigated
      in vivo, mostly by unilateral microdialysis in the dorsal hippocampus. Systemic
      administration of pentylenetetrazole (60 mg/kg, SC), pilocarpine (325 mg/kg, SC),
      bicuculline (6 mg/kg, SC), or kainic acid (10 mg/kg, SC) caused characteristic
      clonic and/or tonic convulsions. In all seizure paradigms, KYNA levels in the
      dialysate began to rise within 1 h and gradually reached a plateau approximately
      4 h after administration of the convulsants. Peak increases were 1.5-3-fold over
      basal levels. The duration of the elevation in KYNA levels was significantly
      prolonged following kainic acid application. In the kainic acid model,
      extracellular KYNA was also measured and found to be increased in the ventral
      hippocampus, piriform cortex, and striatum. Moreover, temporary intrahippocampal
      infusion of the KYN synthesis inhibitor aminooxyacetic acid (1 mM) in the kainic
      acid- and pentylenetetrazole models attenuated the increase in extracellular KYNA
      levels, demonstrating that de novo production of KYNA in the brain accounts for
      the seizure-induced KYNA overflow. A separate group of animals received a
      unilateral intrahippocampal injection of the endogenous convulsant excitotoxin
      quinolinic acid (120 nmol) and showed long-lasting (> 24 h) bilateral increases
      in extracellular KYNA levels. Taken together, these data indicate that an
      increase in extracellular KYNA may constitute a common occurrence in response to
      seizures and that KYNA elevations may signify the brain's attempt to counteract
      seizure activity.

PMID- 8866692
TI  - Memory for the changing cost of a reward is mediated by the sublenticular
      extended amygdala.
AB  - The aim of this study was to examine the role of the sublenticular extended
      amygdala (SEA) in processes of reward and reinforcement. Previous studies have
      examined the effects of ibotenate lesions in this area on motivation for cocaine
      reward. In this study, animals were trained to work for sucrose pellets, rather
      than a drug, on a progressive-ratio schedule of reinforcement. Bilateral
      intracerebral infusions of ibotenic acid (lesion group) or vehicle (control
      group) were made into the SEA, following the same procedures as used in previous
      studies. After recovery from surgery, animals were tested for six sessions on the
      progressive ratio schedule. The lesion did not result in motivational impairments
      of the kind that have previously been reported: rather than decreases in breaking
      point (a measure of motivational strength), the lesion resulted in greater
      variability of breaking points, with a tendency for lesioned animals to work
      harder for reward than controls. The SEA-lesioned rats did not show the increase
      in postreinforcement pause that usually accompanies the increase in perceived
      work as the number of bar presses for a reward increases. Histological analyses
      showed that the ibotenate lesions had successfully destroyed the SEA and that
      damage was also present in adjacent structures. The results are interpreted in
      terms of a mnemonic, rather than a motivational, deficit.

PMID- 8866693
TI  - The lateral preoptic area plays a dual role in the regulation of thirst in the
      rat.
AB  - Electrolyte lesion and ibotenic acid lesion of the lateral preoptic area (LPO) of
      the rat were used to study the participation of this area in drinking behavior.
      Drinking was induced by cellular dehydration, hypovolemia, hypotension, and water
      deprivation. The animals with electrolytic lesion of the LPO showed a significant
      reduction in water intake in response to cellular dehydration, hypotension, and
      deprivation. The animals with ibotenic acid lesion of the LPO increased the water
      consumption produced by subcutaneous (SC) injection of hypertonic saline. The
      amount of water intake after SC injection of polyethyleneglycol (PEG) or
      isoprenaline was similar in control and ibotenic acid-lesioned animals. The rats
      with ibotenic acid lesion of the LPO drank significantly more water than control
      animals. Fibers of passage may also influence the drinking response, and the LPO
      may have osmosensitive receptors that facilitate water intake in connection with
      other areas of the central nervous system (CNS) that are implicated in drinking
      behavior.

PMID- 8866694
TI  - FOS and JUN as markers for ethanol-sensitive pathways in the rat brain.
AB  - The expression of proteins coded by the immediate early genes of the fos family
      and c-jun was used to study the effect of acute ethanol administration on
      convulsant-induced neuronal activity in rat brain. Immunoreactivity for both
      types of protein was induced by either SC injection of pentylenetetrazole or by
      IP injection of N-methyl-D-aspartic acid. Both agents elicited distinct patterns
      of behaviour and a high level of FOS-immunoreactivity in the cerebral cortex and
      hippocampus. Acute IP doses of ethanol (1.0-3.0 g/kg) significantly reduced the
      behaviours and FOS-immunoreactivity induced in the cerebral cortex by both
      pentylenetetrazole and N-methyl-D-aspartic acid. Pentylenetetrazole-induced FOS
      immunoreactivity in the hippocampus was also inhibited by ethanol. In contrast, N
      methyl-D-aspartic acid-induced FOS-immunoreactivity in the hippocampus was not
      inhibited by any dose of ethanol. c-JUN immunoreactivity showed a distinct
      pattern of induction in the hippocampus after injection of N-methyl-D-aspartic
      acid. Ethanol (3.0 g/kg) inhibited N-methyl-D-aspartic acid-induced c-JUN
      immunoreactivity in the hippocampus and cerebral cortex. The differences in
      inhibition of immunoreactivity suggest that the sensitivity of the NMDA- and
      GABAA-related neuronal pathways to ethanol varies among different anatomical
      structures.

PMID- 8866695
TI  - An antisense oligodeoxynucleotide to the delta opioid receptor (DOR-1) inhibits
      morphine tolerance and acute dependence in mice.
AB  - Pharmacological data from several laboratories support a modulatory role for the
      delta opioid receptor in morphine analgesia, tolerance, and physical dependence.
      We examined the role of the delta opioid receptor in these processes using an in
      vivo antisense strategy in mice. Intracerebroventricular administration of a
      20mer antisense or a mismatch control oligodeoxynucleotide (ODN) targeting the
      mRNA of the cloned delta opioid receptor (DOR-1) for 3 days did not affect
      baseline nociceptive thresholds or morphine analgesia compared to untreated or
      saline-treated mice. However, dose-response studies indicate that the induction
      of morphine tolerance following 3 days of chronic morphine administration was
      blocked in antisense but not mismatch ODN or saline-treated mice. Antisense ODN
      treatment also blocked the development of acute morphine dependence, whereas
      similar protection was not afforded to mice treated with saline or mismatch ODN.
      This study demonstrates the relevance of the cloned DOR-1 in morphine tolerance
      and dependence and provides new evidence for a modulatory role of the delta
      opioid receptor using this novel approach.

PMID- 8866696
TI  - Effects of GABA uptake inhibitors on posthypoxic myoclonus in rats.
AB  - Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac
      arrest and resuscitation. Previous results showed that dysfunction of central
      GABAergic neurotransmission may contribute to the disease. In current studies,
      effects of GABA uptake inhibitors, guvacine hydrochloride (1,2,5,6-tetrahydro-3
      pyridine carboxylic acid hydrochloride) and (+/-)-cis-4-hydroxynipecotic acid
      ([+/-]-cis-4-hydroxy-3-piperidine carboxylic acid), in the pathophysiology of
      posthypoxic myoclonus were investigated. Administration of guvacine (1 or 10
      mg/kg, IP) or nipecotic acid (0.5 or 5 mg/kg, IP) significantly attenuated
      myoclonus scores of the animals. Tolerance to antimyoclonus effects of these two
      compounds did not develop after chronic administration (twice a day for 14 days)
      of guvacine (10 mg/kg, IP) or nipecotic acid (5 mg/kg, IP). On the other hand,
      tolerance was noticed with clonazepam (2.5 mg/kg, IP twice a day for 7 days). The
      results indicate that guvacine or nipecotic acid may be used in combination with
      (at reduced doses) or as alternatives to clonazepam to treat patients with the
      disease so as to reduce tolerance phenomenon usually associated with clonazepam.

PMID- 8866697
TI  - Retinoic acid-induced increase in delta-opioid receptor and N-methyl-D-aspartate
      receptor mRNA levels in neuroblastoma x glioma (NG108-15) cells.
AB  - We determined the effects of all-trans retinoic acid (RA) on the levels of delta
      opioid receptor (DOR) mRNA and N-Methyl-D-Aspartate receptor (NMDAR1) mRNA in
      neuroblastoma x glioma hybrid cells (NG108-15) by use of quantitative solution
      hybridization assays. The assays utilized riboprobes complementary to major
      portions of the coding region of the DOR and NMDAR1 cDNAs. At 10 microM RA a 3
      fold increase in DOR mRNA at 48 h, and later (144 h) alterations were observed in
      NMDAR1 mRNA levels. Northern blot analysis revealed six transcripts for DOR mRNA
      ranging in size from 8.7 to 2.0 Kb, and three transcripts for NMDAR1 mRNA ranging
      in size from 4.1 to 3.5 Kb. Neither the size nor the fractional band intensity
      was affected by RA treatment. The delayed induction of DOR mRNA suggests an
      indirect mechanism by which RA acts on transcription of this gene. A surprising
      induction of DOR mRNA by the protein synthesis inhibitor cycloheximide (CHX)
      suggests that either a repressor molecule or degrading enzymes/proteases may
      regulate basal levels of this mRNA. Treatment with RA resulted in a concentration
      and time-dependent morphological differentiation characterized by increased size
      of the cell body and the appearance of numerous short and long processes.

PMID- 8866698
TI  - Effects of alpha-methyl-para-tyrosine (AMPT) in drug-free depressed patients.
AB  - A variety of biologic studies have demonstrated abnormal regulation of the
      norepinephrine (NE) system in patients with major depression, suggesting a role
      for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly
      reduced by blocking synthesis with the tyrosine hydroxylase inhibitor alpha
      methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered
      to drug-free depressed patients to evaluate the effect on mood of diminished
      catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for
      major depressive episode were tested with AMPT and an active placebo control,
      diphenhydramine. Testing was accomplished in a double-blind, crossover fashion,
      with random assignment to test conditions. Each test included baseline
      evaluation, 2 days with administration of either AMPT or diphenhydramine, and a
      follow-up day. Diphenhydramine was used as an active control because of the
      significant sedation associated with AMPT. Behavioral ratings, including visual
      analogue scales for a variety of feeling states, the Hamilton Depression Rating
      Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and
      homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma
      HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT
      also significantly increased visual analogue ratings of "tired" and decreased
      ratings of "energetic." Diphenhydramine significantly decreased HDRS scores, but
      the change was small and was not clinically apparent. The lack of AMPT effects on
      depressed mood, in conjunction with a prior report that large reductions in
      plasma tryptophan do not systematically alter depressed mood, indicate that
      monoamine deficiency by itself is insufficient explanation of the cause of
      depression. The role of the noradrenergic system needs to be considered in
      relationship to the many other neurobiologic factors that could be involved in
      the pathophysiology of depression.

PMID- 8866699
TI  - Cocaine uptake is decreased in the brain of detoxified cocaine abusers.
AB  - Binding of [11C]cocaine in brain was measured with positron emission tomography
      in 12 detoxified cocaine abusers and in 20 controls to evaluate if there were
      changes in cocaine binding and in dopamine (DA) transporter availability
      associated with chronic cocaine use. Nine controls and 10 cocaine abusers had an
      additional scan with [18F]N-methylspiroperidol to measure dopamine D2 receptors.
      Cocaine abusers had significantly lower uptake of [11C]cocaine in brain (6.2 +/-
      1% dose/cc tissues) than controls (7.7 +/- 2%). The distribution volumes (DV) for
      [11C]cocaine were reduced in basal ganglia (BG), cortex, thalamus, and cerebellum
      (CB) of cocaine abusers. However there were no differences in the ratio of the DV
      in BG to that in CB, which is an estimate of DA transporter availability. Values
      for DA D2 receptor availability were decreased in cocaine abusers and did not
      correlate with estimates of dopamine transporter availability. In summary,
      detoxified cocaine abusers showed decreased uptake of cocaine in brain but did
      not show changes in DA transporter availability.

PMID- 8866700
TI  - Neuropsychopharmacology: are we ready for a paradigm shift?
AB  - The "paradigm shift" in the title of this article refers to molecular biology.
      The real challenge to molecular biologists interested in applying their methods
      to an understanding of psychiatric disorders involves the development of models
      that account for gene/environment/development interaction. Because of the
      existence of homologous animal models of addictive disorders, as well as a rich
      body of clinical observations and clinical and behavioral research, and recent
      data suggesting that chronic exposure to addictive drugs results in changes in
      gene expression in neurons from behaviorally relevant brain regions, addictive
      disorders offer a serendipitous model (to molecular biologists) that may have
      relevance to subsequent application in other areas of psychiatry and psychology.

PMID- 8866701
TI  - Altered platelet peripheral-type benzodiazepine receptor in posttraumatic stress
      disorder.
AB  - Peripheral-type benzodiazephine receptors (PBR) are involved in steroidogenesis
      and are sensitive to stress. Reduced platelet PBR density has been demonstrated
      in generalized anxiety disorder (GAD), but not in obsessive-compulsive disorder
      (OCD). We extended this observation to another anxiety disorder, namely,
      posttraumatic stress disorder (PTSD). Eighteen post-Persian Gulf War PTSD
      patients and 17 age- and sex-matched controls were included in the study. All
      subjects were evaluated using the Structured Clinical Interview for DSM-III-R
      Patient Version. The severity of symptoms was assessed using the DSM-III-R scale
      for PTSD, the Impact of Event Scale, the Beck Depression Inventory, and the State
      Trait Anxiety Inventory. [3H]PK 11195 was used to label platelet PBR. All
      psychological parameters (except trait anxiety) were higher in PTSD patients
      compared to controls. Decreased platelet PBR density (-62%; p < .001) was
      observed in the PTSD patients compared to controls. The reduction in PBR observed
      in PTSD patients was in accordance with the findings in GAD patients, but
      differed from those obtained in OCD patients. It is possible that the receptoral
      downregulation is an adaptive response aimed at preventing chronic overproduction
      of glucocorticoids in hyperarousal states.

PMID- 8866702
TI  - The effect of gamma-hydroxybutyric acid on naloxone-precipitated opiate
      withdrawal.
AB  - Because gamma-hydroxybutyric acid (GHB), a GABA metabolite, attenuated
      spontaneous opiate withdrawal in a prior study, we studied GHB's effect on
      naloxone-precipitated opiate withdrawal. Eight opiate-dependent inpatients were
      stabilized on the opioid levorphanol, 18 mg daily. After an initial
      acclimatization challenge, subjects underwent three double-blind challenges on
      consecutive days. Pretreatment in a balanced randomization was with either
      placebo, GHB, 15 mg/kg, or GHB, 30 mg/kg, followed an hour later by intravenous
      naloxone, 0.4 mg/70 kg. GHB produced no significant attenuation of multiple
      withdrawal measures except for hot-cold feelings. GHB pretreatment slightly
      accelerated respiration prior to naloxone. Differences with prior studies may be
      due to (1) timing of GHB administration (giving postwithdrawal in prior studies),
      (2) direct reversal of GHB's anti-withdrawal effects by naloxone, or (3)
      differences between naloxone-precipitated and spontaneous opiate withdrawal.

PMID- 8866703
TI  - beta-adrenergic antagonism alters the behavioral and neurochemical responses to
      cocaine.
AB  - The effects of the beta-adrenergic antagonist propranolol on the locomotor
      stimulating, neurochemical, and reinforcing effects of cocaine were examined in
      rats. In Experiment 1, propranolol (1, 3 and 10 mg/kg, IP) produced a dose
      dependent increase in the motor stimulant effects of cocaine without affecting
      basal motor activity. Atenolol, a peripherally restricted beta 1 antagonist, and
      (+) propranolol, the inactive isomer of propranolol, did not alter cocaine
      induced locomotion. In Experiment 2, propranolol was shown to augment
      significantly the increase in extracellular dopamine content in the nucleus
      accumbens that accompanies a cocaine challenge. Experiment 3 demonstrated that
      propranolol produced a dose-dependent decrease in cocaine self-administration.
      Atenolol (10 mg/kg, IP) reduced cocaine self-administration but to a much lesser
      extent than propranolol. Experiment 4 demonstrated that coadministration of
      propranolol and cocaine did not alter the levels of cocaine in the brain and
      plasma achieved by cocaine administration alone. These data suggest that the
      blockade of beta-adrenergic receptors potentiates cocaine-induced elevation of
      dopamine transmission in the nucleus accumbens, which is associated with an
      increase in cocaine-induced motor activity and a decrease in cocaine self
      administration.

PMID- 8866704
TI  - Effect of cocaine on dopamine transporter receptors depends on routes of chronic
      cocaine administration.
AB  - Investigation of residual behavioral states produced by withdrawal from different
      routes of cocaine administration indicates that depending on the mode of intake,
      chronic cocaine produces either tolerance or sensitization to subsequent
      challenge doses of cocaine. We studied the effect of routes of cocaine
      administration on the dopamine transporter receptors (DATR), the presumed
      neuronal mediator of cocaine reward, using the diphenyl substituted piperazine
      derivative, [3H]GBR 12935 and the cocaine analogue [3H]WIN 35,428. Alzet osmotic
      mini-pumps filled with either cocaine (100 mg/ml) or saline were surgically
      implanted on rats into a subcutaneous pocket at the dorsal midline, continuously
      infusing cocaine at the rate of 40 mg/kg/day. The pumps were removed 14 days
      later, and the rats were killed 7 days after the removal of pumps. For the
      intermittent administration, two groups of rats were injected daily either with
      40 mg/kg of cocaine or saline for 14 days. Rats were killed 7 days following the
      last injection. Continuous infusion of cocaine did not alter the [3H]GBR 12935
      dopamine transporter (DAT) binding either in the caudate nucleus or in the
      prefrontal cortex, but it enhanced the density of [3H]WIN 35,428-labeled DAT
      receptor sites in the caudate putamen. In contrast, intermittent administration
      of cocaine resulted in a selective alteration of [3H]GBR 12935 binding in the
      prefrontal cortex but not in the caudate; the cocaine-injected rats had a 48%
      decrease in [3H]GBR 12935, Bmax (p < .05), without changing the KD. The contrast
      between the lack of effect of cocaine on [3H]GBR 12935-DATR and the increased
      binding of [3H]WIN 35,428-DATR highlights the differential sensitivities of the
      two binding sites to the continuous presence of cocaine.

PMID- 8866705
TI  - The effects of acute and chronic haloperidol treatment on dopamine release
      mediated by the medial forebrain bundle in the striatum and nucleus accumbens.
AB  - The delayed therapeutic effects of neuroleptics have been attributed to D2
      mediated depolarization inactivation (DI) of mesolimbic dopaminergic neurons and
      concomitant reduction in dopamine release. Several studies have suggested,
      however, that DI may not reduce dopamine release and have hypothesized that this
      is due to increased impulse independent release. To examine the mechanisms that
      modulate dopamine release during DI, tetrodotoxin (TTX) was infused into the left
      medial forebrain bundle (MFB) of Sprague Dawley rats. Three-methoxytyramine (3
      MT) levels 10 minutes after pargyline (75 mg/kg) were used as a measure of
      dopamine release. A dose response study showed that infusions of 10(-5) mol/L and
      10(-4) mol/L TTX reduced 3-MT levels on the infused side by 70% in the striatum
      and 50% to 60% in the nucleus accumbens. In a time course study, 10(-5) mol/L TTX
      reduced striatal 3-MT at 30, 90, and 120 minutes. After intraperitoneal
      injections of haloperidol (0.4 mg/kg) for 1 or 21 days, TTX infusions again
      reduced 3-MT levels by approximately 70% in the striatum and 53% to 59% in the
      nucleus accumbens on the infused side. Acute and chronic haloperidol treatment
      did not alter the percent of TTX-induced reductions. These data suggest that
      dopaminergic neuronal impulse flow modulates similar amounts of total transmitter
      release after both acute and chronic haloperidol treatment. The results do not
      support the notion that DI mediates the antipsychotic effects of neuroleptics by
      markedly reducing total basal dopamine release or increasing impulse independent
      release. Alternatively, DI could reduce psychotic symptoms by changing the
      responsiveness of the dopamine system to external stimuli or by reducing synaptic
      dopamine levels that have been hypothesized to be elevated in psychotic patients.

PMID- 8866706
TI  - The cranial nerves of the Senegal bichir, Polypterus senegalus [osteichthyes:
      actinopterygii: cladistia].
AB  - The organization of the roots, ganglia and peripheral distribution of the rami of
      the cranial nerves of larval and juvenile Senegal bichirs was examined with a
      wide range of techniques, including gross dissection and histological
      preparations. The profundal nerve of bichirs is completely separate from the
      trigeminal nerve and innervates the skin overlying the orbit and snout, and there
      is no evidence that a superficial ophthalmic ramus of the trigeminal nerve
      exists. Bichirs appear to retain all six pairs of lateral line nerves that
      characterized the earliest gnathostomes, but the sensory ganglia of the
      anterodorsal and otic lateral line nerves have fused, and the sensory ganglia of
      the anterodorsal and anteroventral lateral line nerves are partially fused, which
      appears to be a shared derived character of ray-finned fishes. The anteroventral
      lateral line nerve of bichirs retains mandibular and opercular rami, a primitive
      feature shared with other bony fishes, and the fibers of the opercular ramus
      innervate all postotic ampullary organs. Surprizingly, bichirs, unlike most
      nonteleost bony fishes, have lost the spiracular organ. The lateral ramus of the
      posterior lateral line nerve of bichirs is divided into a pars dorsalis and a
      pars ventralis, which appears to be a shared derived character of bony fishes.
      The glossopharyngeal and vagal nerves of bichirs exhibit lateral and medial
      sensory ganglia, and this appears to be a shared derived character of bony
      fishes. The posttrematic rami of the glossopharyngeal nerve and both the pre- and
      posttrematic rami of the vagal nerve of bichirs are divided, which appears to be
      a shared derived feature of bony fishes. The hypobranchial nerve of bichirs is
      unusual in that it is formed by only two spinal nerves, a pattern also seen in
      gars, but not other bony fishes, and apparently a uniquely derived character.

PMID- 8866707
TI  - Cytochrome oxidase 'blobs' and other characteristics of primary visual cortex in
      a lemuroid primate, Cheirogaleus medius.
AB  - We recently obtained the brain of a rare lemuroid primate, Cheirogaleus medius.
      The brain was not perfused before death, but rather fixed by immersion shortly
      thereafter. In both flat-mounted and transversely sectioned tissue, we were able
      to clearly demonstrate periodic zones of high cytochrome oxidase (CO) activity in
      the primary visual cortex, resembling the so-called 'blobs' described in many
      other primate species. Our results contrast with a previous report indicating
      that blobs are absent in Cheirogaleus medius and provide support for the view
      that blobs are an evolutionary specialization of primate visual cortex that
      evolved only once, early in primate history. In other aspects of architectonic
      organization, area V1 of this Cheirogaleus individual closely resembles that of
      other strepsirhine primates, such as Galago. We were able to identify additional
      divisions of cortex in this individual, including the middle temporal visual area
      (MT), auditory cortex, and the primary somatosensory area (S1 or area 3b). These
      observations indicate that valuable neuroanatomical information can, in favorable
      cases, be obtained from rare mammalian species that die of natural causes in
      captivity or which must be euthanized, even though the animals have not been
      perfused.

PMID- 8866708
TI  - Ultrastructural morphology of synapses formed by corticostriatal terminals in the
      avian striatum.
AB  - We studied the ultrastructural morphology of corticostriatal projections from two
      different avian 'neocortical' regions, namely, the hyperstriatum accessorium (HA)
      and the pallium externum (PE). Biotinylated dextran amine (BDA) was used to label
      the corticostriatal projection from either HA or PE to the striatum. The
      corticostriatal axons from both the PE and HA possessed numerous beaded
      varicosities with the striatum. These varicosities were filled with numerous
      round vesicles characterizing them as terminals. These terminals formed
      asymmetric synapses with spine heads and with dendrites of striatal neurons. The
      axospinous synapses outnumbered the axodendritic synapses by more than two to
      one. The diameters of labeled axons were typically 250-500 nm. The labeled
      terminals were typically 400-750 nm in diameter. No obvious differences between
      the ultrastructural morphology of the HA and the PE corticostriatal projections
      were observed. These data show that corticostriatal terminals and their synaptic
      contacts in birds are similar to those described in mammals.

PMID- 8866709
TI  - Cholinergic improvement of a naturally-occurring memory deficit in the young rat.
AB  - In a single-trial, passive-avoidance response (PAR) paradigm, young rats at post
      natal day (PND) 16 were found to exhibit a performance deficit that diminished
      progressively with age. When administered prior to training, single peripheral
      injections of cholinomimetic drugs, either a muscarinic agonist (arecoline,
      pilocarpine or oxotremorine), an acetylcholinesterase inhibitor (tacrine or
      E2020), or nicotine, increased the response latencies for young rats to that of
      adult levels in a dose-dependent manner (overall dose range = 0.003 microgram/kg
      10 mg/kg). Neither the cholinergic antagonists scopolamine, atropine or
      mecamylamine, nor a series of non-cholinergic drugs, diazepam, haloperidol,
      phenobarbital, pargyline, D-amphetamine, imipramine, piracetam or N-methyl-D
      aspartate (NMDA) increased PAR latencies. When 0.1 mg/kg scopolamine was given to
      young rats prior to arecoline, the dose-effect curve for enhanced latency times
      was shifted to the right. Higher doses of scopolamine completely blocked the
      effects of arecoline. Scopolamine (0.001-1.0 mg/kg) administered subsequent to,
      rather than before PAR training, blocked the usual arecoline-induced enhancement
      of response latencies. Alternatively, consolidation could be facilitated with
      different doses of tacrine (0.0003-10 mg/kg). These results demonstrate that
      young rats fail to remember the PAR but that retention for this task can be
      specifically enhanced with cholinomimetic drugs.

PMID- 8866710
TI  - Alterations in opiate receptor binding in the hippocampus of aged Long-Evans
      rats.
AB  - Quantitative in vitro autoradiography was used to examine [3H]D-Ala2, MePhe4, Gly
      015 enkephalin (DAGO) (mu-agonist) and [3H]diprenorphine (general opiate
      antagonist) binding sites in the hippocampal formation of young (6-8 months) and
      aged (25-28 months) Long-Evans rats. Age-related changes in these binding sites
      were restricted to specific regions but were not generally dependent on the
      ligand used. No reliable age-related changes in opiate binding were observed in
      the CA1 field or subicular region. In contrast, a decrease in the density of
      binding was found in both dorsal and ventral hippocampus within the CA3 field of
      aged brains. An age-related decrease in opiate binding within the dentate gyrus
      differed in its topography at dorsal and ventral levels of the hippocampus. A
      uniform decrease of opiate receptor binding was found throughout the dorsal
      dentate gyrus, while a more localized decrease of these sites occurred in hilar
      and granular layers of the ventral dentate gyrus. These results indicate that a
      decrease of opiate binding in the hippocampal formation is largely localized to
      the CA3 region and dentate gyrus of aged rats. These findings are discussed with
      reference to age-related changes in hippocampal pathways containing opioid
      peptides. The implications for hippocampal opioid function in learning and age
      related cognitive decline are also considered.

PMID- 8866711
TI  - Synaptophysin immunoreactivity and distributions of calcium-binding proteins
      highlight the functional organization of the rat's dorsal column nuclei.
AB  - The mammalian dorsal column nuclei (DCN) are principally composed of the cuneate
      (CN) and gracile (GN) nuclei. Data presented here support previously published
      anatomical and functional evidence that the longitudinal organization of the CN
      and GN reflect the complex role of the DCN in somatosensory processing. The CN is
      organized longitudinally into three parts. Within the middle portion of this
      nucleus, primary afferent projections and cuneothalamic cells are concentrated.
      Although traditional cytoarchitectonic analyses had failed to detect this
      tripartite organization in rats, we found evidence for it, with a functional
      middle region, extending approximately 0.2-0.9 mm caudal to the obex,
      characterized by precise somatotopy of primary afferent terminations and
      corresponding somatotopy of cytochrome oxidase (CO) blotches. Additional evidence
      is presented here consistent with a functionally distinct middle region within
      the rat's CN: (1) patches of dense synaptophysin (a synaptic-vesical-associated
      protein)-immunoreactivity (SYN-IR) are limited to the middle CN region,
      coincident with the dense CO blotches; (2) neurons immunoreactive for the calcium
      binding proteins calbindin-D28 (CB), calretinin (CR) and parvalbumin (PV) are
      concentrated in the middle CN region. Furthermore, in adult rats subjected to
      perinatal forepaw removal, (1) the patterns of SYN-IR in the middle region of the
      CN are disrupted, as had previously been shown for the patterns of CO blotches;
      (2) in contrast, however, distributions of CN cells with PV-, CB- and CR-IR are
      unaffected. Evidence for a tripartite division in the GN is also presented, based
      on the distributions of cells with PV-, CB- and CR-IR.

PMID- 8866712
TI  - Effects of barbiturates on hypoxic cultures of brain derived microvascular
      endothelial cells.
AB  - An in vitro model of the blood-brain barrier (BBB) consisting of porcine brain
      derived microvascular endothelial cells (BMEC) seeded onto collagen-coated
      polycarbonate membranes was used to investigate the effects of the barbiturates,
      methohexital and thiopental, on permeability properties of the endothelial cell
      monolayer under hypoxia. The permeability of cultured BMEC to ions and sucrose
      increased significantly during 6 h of hypoxia in a reversible manner. Cells were
      resistant to hypoxia for up to 24 h, but 48 h resulted in marked damage as
      assessed by the release of lactate dehydrogenase activity into the culture
      medium. The hypoxia-induced increase of the permeability was unchanged in the
      presence of superoxide dismutase (SOD) and catalase. Methohexital and thiopental
      decreased the hypoxia-induced permeability increase in a concentration-dependent
      manner and permeability changes were abolished completely at the barbiturate
      concentration of 50 micrograms/ml. The barbiturates had no effect on the
      intracellular cAMP content which started to decline after 3 h of hypoxia. Results
      suggest that barbiturates at high concentrations might be able to prevent
      permeability changes of the BBB during cerebral ischemia.

PMID- 8866713
TI  - The effect of basic fibroblast growth factor on glutamate-injured
      neuroarchitecture and arachidonic acid release in adult hippocampal neurons.
AB  - During development in culture, basic fibroblast growth factor (bFGF) protected
      immature primary hippocampal neurons against glutamate-induced neurotoxicity. We
      investigated the effects of bFGF on mature, differentiated rat hippocampal
      neurons cultured for 10-12 days after an 8-min exposure to 500 microM glutamate.
      Seven days post-injury, hippocampal cells demonstrated severe reductions in
      cellular viability and axonal and dendritic outgrowth, which were accompanied by
      a marked increase in [3H]arachidonic acid (ARA) release from prelabelled neurons.
      bFGF applied post-injury attenuated cell death and cytoarchitectural destruction
      at all concentrations used (500 pg/ml, 1, 10, 20 ng/ml). However, neurite
      elongation and branching processes were only significantly protected by 10 ng/ml
      bFGF. [3H]ARA release decreased in a dose-related fashion within a concentration
      range of 1-10 ng/ml bFGF. 20 ng/ml bFGF was not superior to 10 ng/ml bFGF.
      Therefore, bFGF's neurotropic actions appear to be concentration-dependent. Our
      data suggest that bFGF applied post-injury may have a neuroprotective potential
      for mature, differentiated, completely polarized hippocampal neurons.

PMID- 8866714
TI  - Conditioned place preference and locomotor activation produced by injection of
      psychostimulants into ventral pallidum.
AB  - The ventral pallidum (VP) is often viewed as an output structure of the nucleus
      accumbens septi (NAS). However, VP, like NAS, receives a dopaminergic input from
      the ventral tegmental area. These experiments investigated some behavioral
      effects of microinjection into VP of drugs which enhance dopaminergic
      transmission. Injection of 25 micrograms dopamine or 5-10 micrograms amphetamine
      into VP produced hypermotility. In contrast, injection of 12.5-50 micrograms
      cocaine initially suppressed, then increased, activity. Injection of 100
      micrograms cocaine only produced hypomotility in the 1-h period examined. The
      hypomotility following cocaine seemed to be a local anesthetic effect, because it
      was mimicked by 50-200 micrograms procaine. Procaine did not, however, produce
      subsequent hypermotility. Conditioned place preference (CPP) was produced by 10
      micrograms amphetamine and 50 micrograms cocaine but not 100 micrograms procaine.
      We conclude that injection of cocaine into VP unlike similar injections into NAS,
      produces CPP. These results support the idea of an involvement of dopamine in VP
      in reward and locomotor activation, independent of dopamine in NAS. The use of
      intracerebral injections of cocaine is complicated, however, by an apparent local
      anesthetic effect of the drug.

PMID- 8866715
TI  - Effects of selective adenosine A1 and A2a agonists on amphetamine-induced
      locomotion and c-Fos in striatum and nucleus accumbens.
AB  - Low to moderate doses of amphetamine produce locomotion which is dependent on
      release of dopamine in the anteromedial striatum and nucleus accumbens. The
      effects of selective adenosine A1 and A2a receptor agonists on locomotion and c
      Fos induction following a moderate dose of amphetamine was assessed in rats.
      Pretreatment with the adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA)
      or the adenosine A2a receptor agonist 2-[(2
      aminoethylamino)carbonylethylphenylethylamino]-5'-N- ethylcarboxamidoadenosine
      (APEC) inhibited locomotion following an injection of amphetamine (1.5 mg/kg).
      This dose of amphetamine induced Fos-like immunoreactivity in an antero
      dorsomedial distribution in the caudate-putamen and uniformly in the core and
      shell of the nucleus accumbens. Pretreatment with the adenosine A2a receptor
      agonist APEC, but not the adenosine A1 receptor agonist CHA, attenuated c-Fos
      induction in caudate-putamen and nucleus accumbens by amphetamine. These findings
      indicate that amphetamine-induced behavior is subject to modulation by adenosine
      receptors through mechanisms which are both related to and independent of c-Fos
      induction.

PMID- 8866716
TI  - Distribution of acidic fibroblast growth factor-like immunoreactivity in rat
      skeletal muscle fibers.
AB  - Acidic fibroblast growth factor (aFGF) is a mitogenic, angiogenic and
      neurotrophic growth factor which promotes proliferation, but delays
      differentiation of cultured myoblasts. Its mRNA is expressed in the skeletal
      muscle, however, the distribution of aFGF in the postnatal skeletal muscle is
      poorly characterized. In the present study, the distribution of aFGF-like
      immunoreactivity (LI) was examined in developing and adult rat skeletal muscle
      fibers. In addition, the effect of the transection of the sciatic nerve on aFGF
      LI in calf muscle fibers was examined. From the first postnatal day on, aFGF
      immunoreactive (IR) muscle fibers were observed in different calf muscles. From
      the 7th postnatal day on a large number of muscle fibers exhibited aFGF-LI in the
      soleus muscle, some in plantaris and only few in gastrocnemius and extraocular
      muscles. Double-labelling with fast-myosin antibody showed that aFGF-LI was
      restricted to the slow oxidative muscle fibers. aFGF-IR intrafusal muscle fibers
      were seen in developing and mature muscle spindles. In addition, aFGF-IR nerve
      fibers and myoneural junctions were observed in different muscles. Transection of
      the sciatic nerve did not noticeably alter the expression pattern of aFGF-LI in
      calf muscles during two-week period. The present study demonstrates aFGF-LI in
      the rat slow oxidative muscle fibers where it may have fiber-type specific
      functions in addition to its known trophic effects.

PMID- 8866717
TI  - Transforming growth factor alpha differentially affects GABAergic and cholinergic
      neurons in rat medial septal cell cultures.
AB  - The effects of transforming growth factor alpha (TGF alpha) on low and high
      density cultures of fetal (embryonic day 17) rat medial septal cells were
      investigated and in some instances, compared to those of epidermal growth factor
      (EGF). In high density cultures, TGF alpha induces a significant increase in the
      number of astroglia and microglia. While the effects of TGF alpha on the
      astroglia are more pronounced when compared to EGF, those on the microglia are
      less notable. In addition, TGF alpha produces a time- and dose-dependent decrease
      in the activity of choline acetyltransferase (EC 2.3.1.6) and a proportional
      decrease in the number of acetylcholinesterase-positive neurons in these high
      density cultures. However, although both EGF and TGF alpha decreased choline
      acetyltransferase activity maximally at the same concentration (10 ng/ml), the
      latter was consistently more potent. TGF alpha does not affect cholinergic cell
      survival but the expression of their chemical phenotype and does so indirectly
      via the glial cells. On the other hand, TGF alpha directly induces a dose- and
      time-dependent increase in glutamic acid decarboxylase activity in these high
      density cultures without affecting the number of glutamic acid decarboxylase
      immunoreactive neurons. In low density cultures, TGF alpha acts as a general
      neuronal survival factor, affecting both cholinergic and GABAergic neurons. Here
      TGF alpha's neurotrophic activity is more evident than its effects on their
      chemical phenotype. These results suggest that TGF alpha exerts distinct and
      differential effects on the biochemical expression of two neuronal populations in
      the developing medial septum maintained in high density culture. Finally, as TGF
      alpha acts as a general neuronal survival factor in low density cultures, cell to
      cell interactions appear to be important in the ultimate response of these cells
      to this growth factor.

PMID- 8866718
TI  - gamma-aminobutyric acidA receptor regulation: heterologous uncoupling of
      modulatory site interactions induced by chronic steroid, barbiturate,
      benzodiazepine, or GABA treatment in culture.
AB  - Prolonged administration of anxiolytic, sedative, and anticonvulsant drugs that
      act through the GABAA receptor (GABAAR) can evoke tolerance and dependence,
      suggesting the existence of an endogenous mechanism(s) for altering the ability
      of such agents to interact with the GABAAR. Uncoupling appears to be one such
      mechanism. This is a decrease in the allosteric interactions between the
      benzodiazepine (BZD) recognition site and other agonist or modulator sites on the
      GABAAR, as measured by potentiation of [3H]flunitrazepam ([3H]FNZ) binding. To
      investigate the mechanism(s) of uncoupling, neuronal cultures were treated
      chronically with 3 alpha-hydroxy-5 beta-pregnan-20-one (pregnanolone),
      pentobarbital, flurazepam, or GABA, then tested for enhancement of [3H]FNZ
      binding by these substances. The results indicate that BZDs, barbiturates, and
      steroids, as well as GABA itself, are capable of inducing both heterologous and
      homologous uncoupling. Surprisingly, different chronic drug treatments produce
      different patterns of homologous and heterologous uncoupling. Chronic exposure to
      pregnanolone, GABA, flurazepam or pentobarbital induces complete uncoupling of
      barbiturate-BZD site interactions, partial uncoupling of GABA-BZD site
      interactions, but different amounts of uncoupling of steroid-BZD site
      interactions. In addition, the EC50 for pregnanolone-induced homologous
      uncoupling (1.7 microM) is over an order of magnitude greater than that for
      heterologous uncoupling of GABA and BZD sites (82 nM). Moreover, heterologous
      uncoupling by pregnanolone is inhibited by the GABA site antagonist SR-95531,
      whereas homologous uncoupling by pregnanolone is resistant to SR-95531.
      Therefore, there are at least two distinct ways in which GABAAR modulatory site
      interactions can be regulated by chronic drug treatment.

PMID- 8866719
TI  - Cerebral vasodilatation in the cat involves nitric oxide from parasympathetic
      nerves.
AB  - The recent description of the synthesis of nitric oxide (NO) in vivo and its
      putative role in endothelial-dependent vasodilatation has led to considerable
      interest in possible roles for the molecule. In this study the distribution,
      origin and some aspects of the physiology of NO found in the cerebral circulation
      is examined. A rich supply of nerve fibres displaying immunoreactivity against
      nitric oxide synthase (NOS) could be seen in the adventitia of the cat cerebral
      vessels. There was a large number of NOS-positive cells in the sphenopalatine
      ganglion and these constituted a sub-population of the vasoactive intestinal
      polypeptide (VIP) positive cells. Blockade of NOS activity with NG-nitro-L
      arginine methyl ester (L-NAME) significantly attenuated the cerebral vasodilator
      response to facial nerve stimulation when applied locally to the cortex.
      Intravenous administration of L-NAME did not affect the VII-elicited cerebral
      vasodilator response. It may be concluded that the parasympathetic nerves
      innervating the cerebral circulation contain NOS and furthermore, since blockade
      of NOS reduces parasympathetic vasodilatation, that NO is one of the transmitters
      in this system.

PMID- 8866720
TI  - Methamphetamine stimulates the release of neuropeptide Y and noradrenaline from
      the paraventricular nucleus in rats.
AB  - Effects of methamphetamine (MAP) on the extracellular neuropeptide Y (NPY) and
      noradrenaline (NA) levels were examined in the vicinity of the paraventricular
      nucleus (PVN) of freely moving rats by means of push-pull perfusion. The NA and
      NPY levels increased significantly in 30-60 min and reached the maximum level in
      90-120 min after intraperitoneal administration of MAP. The effects were dose
      dependent. The maximum levels were 1.6-fold of the pretreatment level for NPY and
      7-fold for NA, respectively, when 5.0 mg/kg b.w. of methamphetamine was
      administered. It is concluded that MAP stimulates the releases of paraventricular
      NPY and NA, but the effect is more strong for NA than for NPY.

PMID- 8866721
TI  - Chronic antidepressant drug treatment reduces turning behavior and increases
      dopamine levels in the medial prefrontal cortex.
AB  - The effects of chronic administration of the antidepressant drugs desipramine,
      nortryptiline and paroxetine (PAR) (10 mg/kg/day, 21 days) on changes in turning
      (circling) behavior and on norepinephrine (NE), dopamine (DA) and serotonin and
      their metabolites 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole acetic acid
      (5-HIAA) in the medial prefrontal cortex (PFC), nucleus accumbens and striatum
      were evaluated in rats. All three drugs eliminated turning biases in right
      turning rats. All drugs increased DA concentrations in the PFC while PAR
      increased NE in the PFC and reduced 5-HIAA in all three structures. The results
      are discussed with reference to previous findings involving brain asymmetry in
      depression.

PMID- 8866722
TI  - Circadian variation of nitric oxide synthase activity and cytosolic protein
      levels in rat brain.
AB  - The circadian variation of nitric oxide synthase (NOS) activity and cytosolic
      protein content in the cerebellum, brainstem, hypothalamus, hippocampus, and the
      remainder of the brain were studied in rats. Both NOS activity and cytosolic
      protein concentrations were the highest during the dark period and lowest in the
      light period. Hypothalamic NOS activity exhibited the most pronounced change in
      activity with time increasing by approximately 120% from mid-light to mid-dark.

PMID- 8866723
TI  - The determination of the extracellular concentration of brain glutamate using
      quantitative microdialysis.
AB  - Quantitative microdialysis with two enzyme-based assays was used to determine the
      extracellular concentration of glutamate in the striatum of freely moving rats.
      From the difference between infused and dialysate glutamate a value of 3.0 +/-
      0.6 microM for the extracellular glutamate concentration was computed by
      regression analysis. The in vivo recovery, derived from the slope of the
      regression line, was 50%.

PMID- 8866724
TI  - Glutamate, glutamine and glutamine synthetase in the neonatal rat brain following
      hypoxia.
AB  - Exposing 7-day-old rat pups to hypoxia, 8% oxygen/92% nitrogen, for 3 h alters
      glutamate (GLU), glutamine and glutamine synthetase (GS) activity in the
      striatum, frontal cortex and hippocampus. Immediately following the hypoxic
      insult there is a rapid transient elevation of GLU followed by a fall and then
      recovery to control values within 6 h. Glutamine content initially decreased
      after the termination of the insult, rose thereafter and approached control
      values within 6 h. GS activity was depressed after hypoxia and gradually returned
      to normal levels within 6 h. GS mRNA was increased in the three brain regions
      studied after hypoxia and returned to control values within 24 h. These results
      suggest that hypoxia alters GLU metabolism in the immature brain.

PMID- 8866725
TI  - Hypolipidaemic effect of fruit juice of Emblica officinalis in cholesterol-fed
      rabbits.
AB  - The lipid lowering and antiatherosclerotic effects of Emblica officinalis (Amla)
      fresh juice were evaluated in cholesterol-fed rabbits (rendered hyperlipidaemic
      by atherogenic diet and cholesterol feeding). E. officinalis fresh juice was
      administered at a dose of 5 ml/kg body weight per rabbit per day for 60 days.
      Serum cholesterol, TG, phospholipid and LDL levels were lowered by 82%, 66%, 77%
      and 90%, respectively. Similarly, the tissue lipid levels showed a significant
      reduction following E. officinalis juice administration. Aortic plaques were
      regressed. E. officinalis juice treated rabbits excreted more cholesterol and
      phospholipids, suggesting that the mode of absorption was affected. E.
      officinalis juice is an effective hypolipidaemic agent and can be used as a
      pharmaceutical tool in hyperlipidaemic subjects.

PMID- 8866726
TI  - Studies on the immunomodulatory effects of Ashwagandha.
AB  - The immunomodulatory activity of an Indian Ayurvedic medicinal preparation,
      Ashwagandna (Withania somnifera (L. Dunal)) was studied in mice with
      myelosuppression induced by one or more of the following three compounds:
      cyclophosphamide, azathioprin, or prednisolone. The assessment of
      immunomodulatory activity was carried out by hematological and serological tests.
      A significant modulation of immune reactivity was observed in all the three
      animal models used. Ashwagandha prevented myelosuppression in mice treated with
      all three immunosuppressive drugs tested. A significant increase in hemoglobin
      concentration (P < 0.01), red blood cell count (P < 0.01), white blood cell count
      (P < 0.05), platelet count (P < 0.01), and body weight (P < 0.05) was observed in
      Ashwagandha-treated mice as compared with untreated (control) mice. We also
      report an immunostimulatory activity: treatment with Ashwagandha was accompanied
      by significant increases in hemolytic antibody responses towards human
      erythrocytes.

PMID- 8866727
TI  - Effect of Hachimi-jio-gan on scopolamine-induced memory impairment and on
      acetylcholine content in rat brain.
AB  - The effect of Hachimi-jio-gan (HJ) on scopolamine induced memory impairment was
      studied using a radial maze performance, the effect of HJ on the central
      cholinergic system as measured by acetylcholine (ACh) content, choline
      acetyltransferase (CAT) and acetylcholinesterase (AChE) activities was also
      examined. HJ (0.01-1.0 g/kg, p.o.) showed no influence on the radial maze
      performance. However, with the administration of scopolamine (0.5 mg/kg, i.p.),
      the number of the correct choices decreased and the number of the error choices
      increased. HJ (0.1 and 0.5 g/kg, p.o.) reduced this scopolamine-induced cognitive
      disturbance. The effect of HJ on ACh content and enzyme activities in the brain,
      frontal cortex, hippocampus and striatum was also investigated. In normal rats,
      HJ (0.1 and 0.5 g/kg, p.o. x 7 days) significantly increased ACh content in the
      frontal cortex, although it did not increased ACh content in the hippocampus. In
      scopolamine-treated rats, ACh content decreased in the brain regions examined. HJ
      (0.5 g/kg, p.o.) inhibited a decrease in ACh content in the frontal cortex, and
      with the same dosage of HJ increased CAT activity in the frontal cortex and AChE
      activity in the hippocampus. These results suggest that the behavioral effects of
      HJ may be related to its effect on the central cholinergic system.

PMID- 8866728
TI  - Protection by epicoprostanol against hyperglycemia and insulitis in normal and
      diabetic rats.
AB  - Epicoprostanol (3-alpha-hydroxy-5 beta-cholestanol) has been studied for its
      effects on blood glucose and plasma insulin levels in rodents. Epicoprostanol
      significantly induced hypoglycemia and increased insulin levels in rat blood
      plasma by 88% and 66% compared to that of control after 2 h and 4 h of acute
      treatment at 100 mg/kg dose. It also highly significantly lowered blood glucose
      levels in a dose dependent manner at 50, 100 and 200 mg/kg doses when
      administered to alloxan-rendered moderately diabetic rats after 120 and 240 min
      of treatment. Similarly, epicoprostanol, with the same dosage regimen, caused
      hypoglycemia in streptozotocin-induced severe diabetic rats, to a similar extent
      at the same time-points. However, the lowest dose (10 mg/kg) failed to produce a
      striking effect in either of the diabetic groups. In normoglycemic rats, plasma
      insulin levels were affected significantly after a single dose (100 mg/kg) of
      epicoprostanol. In contrast, diabetic animals suffering from insulitis showed a
      significant decline in hyperglycemia, strongly suggesting an insulin-like action
      of epicoprostanol. It seems likely that epicoprostanol acts through a mechanism
      other than hyperinsulinemia.

PMID- 8866729
TI  - Studies on the cytotoxicity, antimicrobial and DNA-binding activities of plants
      used by the Ese'ejas.
AB  - Thirty-nine extracts of 13 plants used traditionally as medicinal by the Ese'ejas
      were studied in order to determine their cytotoxic effect in the brine shrimp.
      Infusions showed no toxicity. Those plants that tested positive for methanolic
      and dichloromethane extracts were assayed for DNA-binding activity. Cytotoxicity
      was not due to the presence of compounds that interact with DNA. Antimicrobial
      activity of plants used to treat infectious diseases was also performed for the
      decoctions. These proved to be active against some of the test microrganisms used
      in the assay.

PMID- 8866730
TI  - Antimicrobial activities of southern Nepalese medicinal plants.
AB  - In an ethnopharmacological screening of selected medicinal plants used in Nepal,
      methanol extracts from 20 plant species were assayed for activity against eleven
      strains of bacteria and four strains of fungi. Duplicate assays were conducted
      with and without exposure to ultraviolet (UV)-A radiation to test for light
      activated or light-enhanced activity. Fifteen of the extracts showed activity
      against bacteria and fourteen showed activity against fungi. Five extracts were
      active only when exposed to UV-A light, and the antibiotic or antifungal effect
      of five extracts was enhanced upon exposure to light. Two of the most active
      extracts were from plants used to treat diarrhoea and dysentery. Bark from both
      Terminalia alata (Combretaceae) and Mallotus phillppensis (Euphorbiaceae) was
      active against Gram-positive and Gram-negative bacteria.

PMID- 8866731
TI  - The effects of extracts from Tetrapleura tetraptera (Taub.) and Bayluscide on
      cells and tissue structures of Biomphalaria glabrata (Say).
AB  - Subchronic experiments were conducted with low concentrations of saponins from
      Tetrapleura tetraptera and Bayluscide to study the ultrastructural effects of
      these molluscicides on Biomphalaria glabrata. The ratio of the digestive cells to
      the crypt cells was inverted in molluscicide treated snails which showed an
      increase in the number of secretory cells and a decrease in the number of
      digestive cells. In the snail foot connective tissues, dose-dependent autolytic
      areas were observed. The major ultrastructural effects were seen in the digestive
      gland with dose-dependent autolysis of the membranous structures such as the
      golgi apparatus, mitochondria and endoplasmic reticulum. The results show that
      the molluscicides produced non-specific effects on the membranous structures.

PMID- 8866732
TI  - Body temperature and nesting behavior following influenza challenge in mice:
      effects of age.
AB  - We studied the interaction of age and influenza on core body temperature (Tc) of
      mice. Following influenza challenge, 2-mo-old female BALB/c mice demonstrated a
      significant fall in Tc. Female BALB/c mice 24 mo of age had lower baseline Tc
      than young mice and a larger fall in Tc post influenza challenge. We noted there
      were marked differences in nesting behavior between the young and aged mice. A
      nesting score was devised, and we found that at baseline, aged mice had a much
      lower score than young mice (15.6 +/- 7.4 vs. 24.7 +/- 0.3, P < 0.0001).
      Following influenza challenge, nesting behavior of young mice dropped
      considerably, while no significant change occurred in the behavior of aged mice.
      When mice were housed without bedding, there were significant decreases in Tc of
      young, but not aged mice. There was a further fall in Tc with influenza challenge
      in young mice. These data imply that nesting is an important mechanism for
      maintaining Tc in young mice, but alternative mechanisms are used by aged mice.
      The lower body temperatures in the aged mice are similar to studies in aging
      humans.

PMID- 8866734
TI  - Changes in En(a-) human red blood cell membranes during in vivo ageing.
AB  - The human red blood cells with phenotype En(a-) were characterized by the lack of
      MN antigens. The red blood cells with phenotype En(a-) which were found in a
      Japanese family were tested to clarify the changes in membrane surfaces of the
      red blood cells during in vivo ageing. The contents of sialic acid, glucose,
      mannose, galactose, fucose, N-acetylglucosamine and N-acetylgalactosamine of the
      red blood cell membranes obtained from the old red blood cells with phenotype
      En(a-) were significantly lower than those of the young red blood cell membranes.
      Neither the young nor the old red blood cells with phenotype En(a-) showed the
      agglutination with Arachis hypogaea (PNA) which was capable of binding to T
      agglutinogen. It is presumed that En(a-) red blood cells are not exposed to
      sialidase in vivo. In comparison with the young En(a-) red blood cell membranes,
      the number and the distribution density of lectin receptor sites on the old ones
      for Limulus polyphemus (LPA), Canavalia ensiformis (Con A), Triticum vulgaris
      (WGA) and Bauhinia purpurea (BPA) were significantly lower. It is thought that
      En(a-) red blood cell ageing is accompanied by elimination of some
      sialoglycoconjugates which have affinity for LPA, Con A, WGA and BPA, whereas
      En(a-) red blood cells lack glycophorin A.

PMID- 8866733
TI  - cAMP signaling mechanisms with aging in rats.
AB  - Blunted cAMP responses to beta-adrenergic agonists play a major role in
      diminished smooth muscle relaxation in blood vessels from older animals, although
      the mechanisms remain uncertain. A diminished cAMP response could potentially
      arise from changes in the expression of adenylyl cyclase-coupled G proteins, such
      as a diminished expression of Gs or an increased expression of Gi. We tested the
      hypothesis that a loss in Gs or increased expression of Gi could occur in tissues
      such as the aorta, heart and kidney with aging, which would provide a unifying
      explanation for blunted cAMP responses to many hormones with aging in a variety
      of cells. Using Western blotting with specific antibodies, we found no
      generalized changes in G protein expression with aging. Also, injection of
      pertussis toxin (which functionally inactivates Gi) into older animals did not
      restore vascular relaxation mediated by beta-adrenergic receptors. We previously
      found an elevated ratio of regulatory to catalytic subunits of protein kinase A
      in the aorta of older rats, which would tend to impair activation of the
      catalytic unit; this alteration was not generalized to other organs such as the
      heart and kidney. Old rats fed a low salt diet did not show the restored beta
      adrenergic agonist-induced vasodilation previously found in elderly humans,
      suggesting that there are species differences in the development of this deficit.
      Altogether, these results suggest that altered G protein expression does not
      provide a general explanation for blunted activation of adenylyl cyclase with
      aging.

PMID- 8866735
TI  - Age-related changes in amylin secretion.
AB  - Amylin (islet amyloid polypeptide) is a recently identified pancreatic peptide.
      It has been shown to affect glucose metabolism both in vitro and in vivo. A cross
      sectional analysis of the effects of age on amylin secretion following a 75 g
      glucose tolerance test in a young (20-40 years), middle aged (41-60 years) and
      older (61-90 years) group was performed. Thirty lean (BMI less than 25) non
      diabetic individuals were studied. Amylin secretion exhibited a U-shaped curve
      with greater secretion in young and old subjects than in middle aged persons.
      Baseline levels were 7.2 +/- 1, 4.7 +/- 1, and 5.3 +/- 0.75 pM respectively, at
      60 min 9.5 +/- 0.9 (y), 5.5 +/- 1 (m), 8.6 +/- 1 (o) pM; and at 120 min 10.3 +/-
      2 (y), 4.4 +/- 0.5 (m), 10.9 +/- 1.5 (o) pM. Amylin production (area under the
      curve) was 1102 +/- 131, 619.5 +/- 79 and 1043 +/- 120 pM per min respectively (P
      < 0.05). Amylin secretion was similar in both sexes. Variability in the insulin
      to amylin ratio for each of the age groups at different time points following a
      glucose load was found, suggesting that insulin and amylin are not co-secreted in
      a fixed ratio. A significant association was found between both maximum amylin
      and rise in amylin (delta) and a glucose greater than 120 mg/dl at 2 h. (P <
      0.001, P < 0.001). This correlation of glucose and amylin may be interpreted as
      suggestive of a counterregulatory role for amylin. However, aging is also
      associated with changes in glucose metabolism and amylin may merely be acting as
      a marker of impaired glucose metabolism.

PMID- 8866736
TI  - Low fatty acid unsaturation protects against lipid peroxidation in liver
      mitochondria from long-lived species: the pigeon and human case.
AB  - Birds have a much higher maximum longevity (MLSP) than mammals of similar
      metabolic rate. Recent data showed that pigeon mitochondria produce oxygen
      radicals at a rate much slower than rat mitochondria, in spite of showing similar
      levels of oxygen consumption (Free Rad. Res., 21 (1994) 317-328). Since oxidative
      damage from and to mitochondria seems important in relation to aging and
      longevity, and mitochondrial membranes are situated at the place where oxygen
      radicals are generated, we studied protein and lipid peroxidation and fatty acid
      composition of the three main membrane phospholipids of liver mitochondria from
      rats (MLSP = 4 years) and pigeons (MLSP = 35 years). It was found that pigeon
      mitochondria show lower levels of fatty acid unsaturation than rat mitochondria
      in the three lipid fractions, mainly due to a substitution of highly unsaturated
      fatty acids (20:4 and 22:6) by linoleic acid (18:2), and that these mitochondria
      are more resistant to lipid peroxidation. Previous research has also obtained
      exactly the same major difference in fatty acid composition in human mitochondria
      when compared to those of rat. Thus, present information suggests that the liver
      mitochondrial membranes of especially long-lived species show both a low level of
      free radical production and a low degree of fatty acid unsaturation as important
      constitutive protective traits to slow down aging.

PMID- 8866737
TI  - Change of the lipid hydroperoxide level in mouse organs on ageing.
AB  - Change in the total level of tissue lipid hydroperoxides during ageing in the
      mouse was determined by our newly developed specific and sensitive method. The
      hepatic level of lipid hydroperoxides of 5-week-old mice was 239 +/- 31 pmol/mg
      protein. Hydroperoxide levels in the liver of 20-, 30-, 40-, 60- and 85-week-old
      groups were 487 +/- 115, 348 +/- 87, 395 +/- 65, 498 +/- 98 and 431 +/- 81
      pmol/mg protein, respectively, and these values were significantly higher than
      the content of the 5-week-old animals. In the heart and kidney, the level of
      lipid hydroperoxides increased also significantly at 20 weeks of age compared
      with that of the 5 week-old mouse. The hydroperoxide level did not increase
      significantly thereafter until 85 weeks of age. The hydroperoxide level in the
      brain did not change during 5-85 weeks of age.

PMID- 8866738
TI  - On the plausibility of "the neurodevelopmental hypothesis" of schizophrenia.
AB  - Speculation that schizophrenia is associated with abnormal brain development, the
      so-called neurodevelopmental hypothesis, has become so popular that it is rarely
      challenged in the literature. This paper critically examines the evidence for
      this hypothesis, taking primarily the "devil's advocate" position. The evidence
      from neuroimaging studies, from studies of prenatal and perinatal intrauterine
      events and of premorbid development are circumstantial with respect to brain
      development, many studies are methodologically flawed, and most do not exclude
      alternative explanations. Evidence from postmortem studies of anomalous
      cytoarchitecture in limbic and prefrontal cortices is especially noteworthy, as a
      developmental defect is virtually certain if artifacts can be excluded.
      Unfortunately, the studies responsible for these findings have serious
      methodological limitations. The neurobiological plausibility of the hypothesis,
      which might have been predicted to be its weakest aspect, has proved surprisingly
      unshakeable in a recent series of animal studies. Ironically, the principal
      weakness of the neurodevelopmental hypothesis at present is the clinical database
      on which it rests.

PMID- 8866739
TI  - Psychobiologic correlates of treatment response in schizophrenia.
AB  - In studies conducted on largely treatment naive patients in their first episode
      of psychosis, we have found that treatment outcome is quite good and that most
      patients recover or at least achieve a substantial degree of symptom remission.
      However, over the course of their illness and in the context of subsequent
      psychotic episodes, they may experience some decrease in their treatment response
      from illness progression. In addition, the heterogeneity of treatment outcome is
      associated with specific clinical (gender, primary negative symptoms of the
      deficit state, duration of psychosis) and biological variables (pHVA, ventricular
      volume). It is unclear whether these variables represent aspects of discrete
      subtypes of schizophrenia or dimensional measures of pathology within the broad
      context of a unitary disease entity.

PMID- 8866740
TI  - Clinical and biological markers for outcome in schizophrenia: a review of a
      longitudinal follow-up study in Uppsala schizophrenia research project.
AB  - During a 10-year period, 120 drugfree DSM-III-R schizophrenic patients were
      consecutively and unselectively admitted to a ward for young psychotic patients
      and subjected to a battery of examinations including symptomatology,
      cerebrospinal fluid (CSF)-biochemistry, computed tomography (CT)-scan,
      neurophysiologic and psychophysiologic (Electrodermal activity, EDA) parameters
      before antipsychotic treatment was initiated. After discharge, the patients were
      longitudinally followed with ratings of outcome (Strauss-Carpenters outcome
      scale) at years 1, 3, and 5 after index admission. The aim of the study was to
      find possible early markers for outcome in schizophrenia. At 5 years, 30% of the
      patients had a good outcome (total score > 13) and 15% a poor outcome (total
      score < 8). Poor premorbid adjustment and low level of education as well as
      negative schizophrenic symptomatology at index admission were associated with a
      poor outcome 5 years later. Positive symptomatology and a family history of
      schizophrenia did not predict outcome. Patients with a poor outcome (total score
      < 8) had a significantly more deviant CSF HVA/5-HIAA quotient than those with a
      very good outcome (total score > 15) as compared with healthy controls. Further,
      the CSF-peptides neuropeptide Y, dynorphin A, and CRF were predictable for
      outcome at the 5-year follow-up evaluation. Male schizophrenics who were
      "nonresponders" on the EDA test showed an almost 100% poor outcome, which was not
      found in females. In summary, several clinical and biological variables seem to
      have a predictable value for outcome in schizophrenia and, early identification
      of them might be a challenge for our future treatment strategies.

PMID- 8866741
TI  - Neuropsychologic deficits in schizophrenia: relation to social function and
      effect of antipsychotic drug treatment.
AB  - Cognitive impairment is present in the majority of schizophrenic patients, even
      at the onset of psychosis. It is a relatively stable characteristic in most
      patients, usually with little progression over the course of illness, but
      sometimes progresses to severe dementia. The results of studies of the effects of
      typical neuroleptic drugs on cognitive functioning in schizophrenia are
      conflicting. Clozapine, which has superior antipsychotic effects compared to
      typical neuroleptic drugs, has been reported to improve executive function,
      verbal fluency, attention, and recall memory in two of three studies. Cognitive
      measures predict work function and overall outcome on clozapine as assessed by
      the Global Assessment Scale and Quality-of-Life Scale in neuroleptic--resistant
      schizophrenia. Improvement in cognitive function by clozapine may be a major
      reason for expanding its currently limited utilization.

PMID- 8866742
TI  - Extrapyramidal symptoms during long-term treatment with antipsychotics: special
      focus on clozapine and D1 and D2 dopamine antagonists.
AB  - In schizophrenic patients in maintenance treatment, clozapine, compared to
      classic neuroleptics, induces relatively few extrapyramidal syndromes (EPS),
      especially less akathisia and tremor and usually no dystonia or rigidity. In
      patients with dyskinetic movements (acute or tardive) induced by other
      neuroleptics, clozapine may reduce or even remove dyskinesia or permit it to
      disappear. It cannot, however, be excluded that clozapine can induce dyskinesia
      in extremely rare cases, but it seems more likely that this is due to previous
      treatment with classic neuroleptics. The earlier clozapine is started, the less
      chance of development of dyskinesia. The low level of EPS with clozapine may be
      linked to the special receptor-binding profile of this drug: during treatment
      with therapeutic doses of clozapine, the level of D2 receptor blockade is too low
      (40% to 50% occupancy by positron emission tomography) to induce EPS, and the D1
      receptor blockade (also 40% to 50% occupancy) has a lower EPS potential than D2
      blockade. This binding profile may at the same time contribute to the special
      antipsychotic properties of clozapine. Other receptor affinities may contribute
      to the beneficial effect of clozapine in EPS and schizophrenia.

PMID- 8866743
TI  - Neuropathology of early HIV-1 infection.
AB  - Early HIV-1 invasion of the central nervous system has been demonstrated by many
      cerebrospinal fluid studies; however, most HIV-1 carriers remain neurologically
      unimpaired during the so called "asymptomatic" period lasting from seroconversion
      to symptomatic AIDS. Therefore, neuropathological studies in the early pre-AIDS
      stages are very few, and the natural history of central nervous system changes in
      HIV-1 infection remains poorly understood. Examination of brains of asymptomatic
      HIV-1 positive individuals who died accidentally and of rare cases with acute
      fatal encephalopathy revealing HIV infection, and comparison with experimental
      simian immunodeficiency virus and feline immunodeficiency virus infections
      suggest that, invasion of the CNS by HIV-1 occurs at the time of primary
      infection and induces an immunological process in the central nervous system.
      This includes an inflammatory T-cell reaction with vasculitis and
      leptomeningitis, and immune activation of brain parenchyma with increased number
      of microglial cells, upregulation of major histocompatibility complex class II
      antigens and local production of cytokines. Myelin pallor and gliosis of the
      white matter are usually found and are likely to be the consequence of opening of
      the blood brain barrier due to vasculitis; direct damage to oligodendrocytes by
      cytokines may also interfere. These white matter changes may explain, at least
      partly, the early cerebral atrophy observed, by magnetic resonance imaging, in
      asymptomatic HIV-1 carriers. In contrast, cortical damage seems to be a late
      event in the course of HIV-1 infection. There is no significant neuronal loss at
      the early stages of the disease, no accompanying increase in glial fibrillary
      acid protein staining in the cortex, and only exceptional neuronal apoptosis.
      Although HIV-1 proviral DNA may be demonstrated in a number of brains, viral
      replication remains very low during the asymptomatic stage of HIV-1 infection.
      This makes it likely that, although opening of the blood brain barrier may
      facilitate viral entry into the brain, specific immune responses including both
      neutralising antibodies and cytotoxic T-lymphocytes, continuously inhibits viral
      replication at that stage.

PMID- 8866744
TI  - Dystrophin-associated proteins and the muscular dystrophies: a glossary.

PMID- 8866745
TI  - Dystrophin and its isoforms.

PMID- 8866746
TI  - Utrophin: a structural and functional comparison to dystrophin.
AB  - Utrophin is an autosomally-encoded homologue of dystrophin, the protein product
      of the Duchenne muscular dystrophy (DMD) gene. Although, utrophin is very similar
      in sequence to dystrophin and possesses many of the protein-binding properties
      ascribed to dystrophin, both proteins are expressed in an apparently reciprocal
      manner and may be coordinately regulated. In normal skeletal muscle, utrophin is
      found at the neuromuscular junction (NMJ) whereas dystrophin predominates at the
      sarcolemma. However, during development, and in some myopathies including DMD,
      utrophin is also found at the sarcolemma. This re-distribution is often
      associated with a significant increase in the levels of utrophin. At the NMJ
      utrophin co-localizes with the acetylcholine receptors (AChR) and may play a role
      in the stabilization of the synaptic cytoskeleton. Because utrophin and
      dystrophin are so similar, utrophin may be able to replace dystrophin in
      dystrophin deficient muscle. This review compares the structure and function of
      utrophin to dystrophin and discusses the rationale behind the use of utrophin as
      a potential therapeutic agent.

PMID- 8866747
TI  - Clinical and histopathological features of abnormalities of the dystrophin-based
      membrane cytoskeleton.
AB  - The majority (approximately 70%) of cases of childhood and adult onset muscular
      dystrophies in males, and approximately 10% of dystrophy in girls and women, show
      underlying primary abnormalities of dystrophin. Approximately 2% of
      childhood/adult onset muscular dystrophy patients have a primary defect of one of
      the three sarcoglycan proteins identified to date (alpha, beta, gamma). The
      finding of a sarcoglycan deficiency in muscle generally does not reflect the
      primary underlying defect, and thus testing of biopsies for sarcoglycans should
      be used only after normal dystrophin findings, and in conjunction with gene
      mutation testing. Approximately 30% of neonatal onset congenital muscular
      dystrophy has been shown to be due alpha 2-laminin (merosin) deficiency. alpha 2
      laminin is a component of the myofiber basal lamina, and this protein interacts
      with the dystrophin-based membrane cytoskeleton. Due to the similar clinical and
      histopathological features of the different etiologies of muscular dystrophies,
      molecular testing of peripheral blood DNA and muscle biopsy protein are a
      critical part of the clinical work-up of dystrophy patients. Many patients
      carrying a Becker dystrophy or limb-girdle dystrophy diagnosis should be re
      evaluated with molecular tests to provide accurate genetic counseling to their
      families.

PMID- 8866748
TI  - Dystrophin in the nervous system.

PMID- 8866749
TI  - Pivotal role of renal kallikrein-kinin system in the development of hypertension
      and approaches to new drugs based on this relationship.
AB  - Renal kallikrein is one of the tissue kallikreins, and the distal nephron is
      fully equipped as an element of the kallikrein-kinin system. Although a low
      excretion of urinary kallikrein has been reported in essential hypertension, the
      results from studies on patients with hypertension are not consistent.
      Congenitally hypertensive animals also excrete lowered levels of urinary
      kallikrein, but the effects of this are yet unknown. Extensive genetic and
      environmental studies on large Utah pedigrees suggest that the causes of
      hypertension are closely related to the combination of low kallikrein excretion
      and the potassium intake. Mutant kininogen-deficient Brown Norway-Katholiek rats,
      which cannot generate kinin in the urine, are very sensitive to salt loading and
      to sodium retention by aldosterone released by a non-pressor dose of angiotensin
      II, which results in hypertension. The major function of renal kallikrein-kinin
      system is to excrete sodium and water when excess sodium is present in the body.
      Failure of this function causes accumulation of sodium in the cerebrospinal fluid
      and erythrocytes, and probably in the vascular smooth muscle, which become
      sensitive to vasoconstrictors. We hypothesize that impaired function of the renal
      kallikrein-kinin system may play a pivotal role in the early development of
      hypertension. Inhibitors of kinin degradation in renal tubules and agents, which
      accelerate the secretion of urinary kallikrein from the connecting tubules and
      increase the generation of urinary kinin, may be novel drugs against
      hypertension.

PMID- 8866750
TI  - Antiarrhythmic and proarrhythmic effects of sematilide in canine ventricular
      arrhythmia models.
AB  - Using canine ventricular arrhythmia models induced by two-stage coronary
      ligation, digitalis, adrenaline, coronary ligation and reperfusion, and
      programmed electrical stimulation (PES), we examined the antiarrhythmic or
      proarrhythmic effects of sematilide, N-[2(diethylamino)ethyl]-4
      [(methylsulfonyl)amino]-benzamide hydrochloride. Sematilide in an intravenous
      (i.v.) dose range of 0.3 to 6.0 mg/kg prolonged the QTc interval, but had an
      antiarrhythmic effect only on the arrhythmias induced by PES (7 out of 10 dogs
      with old myocardial infarction). Sematilide was not effective on coronary
      ligation and reperfusion arrhythmia or the spontaneously occurring automaticity
      arrhythmias induced by two-stage coronary ligation, digitalis and adrenaline,
      respectively, and even aggravated digitalis- and adrenaline-induced arrhythmias.
      These results indicate that the class III agent sematilide is similar to other
      new class III agents, such as d-sotalol, E-4031 and MS-551, in that it was not
      effective on the automaticity arrhythmias, but different from these new class III
      agents, in that sematilide prevented only the induction of ventricular
      arrhythmias induced by PES and did not suppress the coronary ligation-reperfusion
      arrhythmias. The PES induced arrhythmias are thought to be induced exclusively by
      a reentrant mechanism, but the reperfusion arrhythmias may involve not only re
      entry, but also automaticity, and we reported the effectiveness of MS-551, E-4031
      and d-sotalol on the latter arrhythmia. Sematilide is different in that it even
      aggravated some automaticity arrhythmias.

PMID- 8866751
TI  - Leukopenia-inducing effect of a combination of a new 5-fluorouracil (5-FU)
      derived drug, BOF-A2 (emitefur), with other 5-FU-derived drugs or BV-araU
      (sorivudine) in rats.
AB  - BOF-A2 (emitefur: 3-(3-[6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl]benzoyl)-1
      ethoxy- methyl-5- fluorouracil), a novel 5-FU (5-fluorouracil)-derived drug, was
      co-administered with other conventional 5-FU-derived drugs or BV-araU
      [sorivudine: 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyluracil)] for 8
      consecutive days to rats. BOF-A2 (6 or 8 mg/kg, p.o.) co-administered with other
      5-FU-derived drugs elevated the plasma 5-FU concentration 3- to 23.3-fold and
      decreased the peripheral white blood cell (WBC). The percentage decreases of WBC
      by 5-FU (4 mg/kg, i.p.), UFT (16 mg/kg, p.o.), tegafur (FT; 16 mg/kg, p.o.),
      carmofur (HCFU; 15 mg/kg, p.o.), doxifluridine (5'-DFUR; 16 mg/kg, p.o.) and
      flucytosine (200 mg/kg, p.o.) were 25.7%, 31.9%, 70.3%, 32.0%, 58.6% and 30.0%,
      respectively, compared with each drug alone. On the other hand, these phenomena
      did not occur with BV-araU. These findings can be attributed to the fact that the
      inhibitory activity of CNDP (3-cyano-2,6-dihydroxypyridine) for 5-FU degradation
      (IC50: 6.3 x 10(-9) M) is potent and 6000 times greater than that of BVU [(E)-5
      (2-bromovinyl) uracil], another inhibitor of 5-FU degradation.

PMID- 8866752
TI  - Preservation of endothelium-dependent vascular relaxation in cholesterol-fed mice
      by the chronic administration of prazosin or pravastatin.
AB  - The relaxation of aortic rings in response to acetylcholine (ACh) was
      significantly decreased in cholesterol-fed mice. The attenuated relaxation in
      cholesterol-fed mice was preserved by the chronic administration of prazosin (20
      mg/kg/day) or pravastatin (12.5 mg/kg/day). Serum low-density lipoprotein (LDL)
      levels were significantly increased in mice given cholesterol. The increased
      serum LDL levels in cholesterol-fed mice were returned to normal by the chronic
      administration of prazosin and pravastatin. A prior incubation of aortic rings
      with lysophosphatidylcholine (LPC) significantly attenuated ACh- and A23187
      induced endothelium-dependent relaxation. The inhibitory effects of LPC on
      endothelium-dependent relaxation were not affected by indomethacin or superoxide
      dismutase. The sodium nitroprusside-induced relaxation of aortic rings was not
      changed by LPC. The inhibitory effects on ACh-induced relaxation by NG-monomethyl
      L-arginine were restored by a prior exposure to L-arginine, whereas the
      inhibition of endothelium-dependent relaxation by LPC was not affected by L
      arginine. These results suggest that cholesterol-fed mice are useful animal
      models of hypercholesterolemia, and chronic administration of prazosin or
      pravastatin can preserve endothelium-dependent relaxation by lowering serum LDL
      in these animals. It is further suggested that LPC derived from oxidized LDL may
      be involved in the reduced endothelium-dependent relaxation in hyperlipidemia.

PMID- 8866753
TI  - Acteoside, a component of Stachys sieboldii MIQ, may be a promising antinephritic
      agent (3): effect of aceteoside on expression of intercellular adhesion molecule
      1 in experimental nephritic glomeruli in rats and cultured endothelial cells.
AB  - It is known that adhesion molecules play a crucial role in the development of
      glomerulonephritis. Therefore, we investigated the effects of acteoside on the
      expression of intercellular adhesion molecule-1 (ICAM-1) in nephritic glomeruli,
      in vivo, and human umbilical vein endothelial cells (HUVECs) and rat mesangial
      cells, in vitro. Aceteoside treatment significantly decreased the up-regulation
      of ICAM-1 expression in nephritic glomeruli. Acteoside prevented the up
      regulation of ICAM-1 expression mediated by inflammatory cytokines or phorbol 12
      myristate 13-acetate on HUVECs and rat mesangial cells. Adhesion of neutrophils
      and macrophages to acteoside-treated HUVECs was suppressed to one half of that in
      untreated HUVECs. These data support the finding that acteoside inhibits the up
      regulation of ICAM-1 in the nephritic glomeruli. Additionally, it is suggested
      that the antinephritic action of acteoside is due to the inhibition of
      intraglomerular accumulation of leukocytes through the prevention of the up
      regulation of ICAM-1. This is the first paper demonstrating that the up
      regulation of ICAM-1 in nephritic glomeruli is inhibited by a natural product,
      acteoside.

PMID- 8866754
TI  - Effect of mizoribine on collagen-induced arthritis in mice.
AB  - This study examines the effect of mizoribine (MZR), an immunosuppressant, on
      collagen-induced arthritis in mice. DBA/1J mice, immunized on days 0 and 21 with
      200 micrograms of type II collagen in complete Freund adjuvant, were treated with
      various doses of MZR for 12 weeks, beginning on the day after the primary
      immunization. MZR reduced the arthritis score in a dose-dependent fashion,
      showing significant suppression, even at a dose of 10 mg/kg. At doses of more
      than 20 mg/kg, MZR also significantly suppressed bone damage in the hind limbs.
      MZR significantly suppressed the delayed-type hypersensitivity response to type
      II collagen, but only slightly decreased anti-type II collagen antibody levels.
      MZR restored the L3T4+/Lyt-2+ ratio, which was increased in arthritic mice, to
      the level found in normal mice. These findings show that MZR suppresses collagen
      induced arthritis and bone damage in mice, and suggest that the inhibitory effect
      of MZR is based on its suppression of cellular immunity. These results provide a
      theoretical basis for the clinical use of MZR in rheumatoid arthritis.

PMID- 8866755
TI  - Effects of beraprost sodium, a prostacyclin analogue, on diabetic neuropathy in
      streptozotocin-induced diabetic rats.
AB  - The effects of beraprost sodium (BPS), a stable prostacyclin analogue, on motor
      nerve conduction velocity and nerve blood flow of the sciatic nerve were
      investigated in streptozotocin-induced diabetic rats, and they were compared with
      the effects of epalrestat (aldose reductase inhibitor). Treatment with BPS for 4
      weeks significantly inhibited the decrease in motor nerve conduction velocity and
      nerve blood flow dose-dependently, but epalrestat had no effect on nerve blood
      flow. Morphological changes of the myelinated fibers of the sciatic nerve were
      observed macroscopically. The mean axonal area and the mean circularity index of
      diabetic control rats were significantly less than that of normal rats, while
      after 6 weeks of BPS treatment, these decreases of the axonal area and the
      circularity index were inhibited. The enlargement of the mean lumen area of
      microvessels in the diabetic rats was significantly inhibited after 6 weeks of
      BPS treatment. Additionally, augmentation of the washed platelet aggregation in
      diabetic rats was significantly normalized by BPS. It was suggested that BPS is
      effective on diabetic neuropathy via amelioration of the decrease of blood supply
      to the structure. The effects of BPS on platelets might also contribute to the
      improvement of neuronal circulatory deficiency.

PMID- 8866756
TI  - Effects of KSG-504, a new cholecystokinin-A-receptor antagonist, on pancreatic
      exocrine and endocrine secretions in rats.
AB  - The effects of KSG-504 ((S)-arginium (R)-4-[N-(3-methoxypropyl)-N
      pentylcarbamoyl]-5-(2-naphthylsulf onyl) pentanoate monohydrate), a new
      cholecystokinin (CCK)-A-receptor antagonist, on pancreatic exocrine secretion in
      anesthetized rats and endocrine secretion in conscious rats were studied.
      Intravenous injection of KSG-504 inhibited the pancreatic amylase output
      stimulated by intravenous infusion of CCK-8 in a dose-dependent manner (ED50: 18
      micrograms/kg/min). Moreover, KSG-504 significantly reduced the CCK-8-stimulated
      increases in pancreatic juice volume and outputs of protein, trypsin and lipase.
      Intraduodenal infusion of casein increased the plasma CCK concentration and the
      pancreatic amylase output. KSG-504 significantly inhibited the pancreatic amylase
      output stimulated by casein. Pancreatic juice volume and bicarbonate output were
      significantly stimulated by intravenous infusion of secretin, but were not
      changed by KSG-504. When pancreatic exocrine secretion was stimulated by secretin
      plus CCK-8, KSG-504 suppressed the increases in juice volume and bicarbonate
      output to the level stimulated by secretin alone. Basal pancreatic amylase output
      was decreased by KSG-504. KSG-504 decreased the level of plasma immunoreactive
      insulin (IRI) stimulated by glucose plus CCK-8, but had no effect on IRI
      stimulated by glucose alone and the basal IRI. These in vivo studies suggest that
      KSG-504 has significant inhibitory effects both on the pancreatic exocrine and
      endocrine secretion stimulated by CCK, but has no effect on the exocrine
      secretion stimulated by secretin.

PMID- 8866757
TI  - Betaxolol, a beta 1-adrenoceptor antagonist, inhibits Ca(2+)-induced contraction
      in skinned renal artery of the dog.
AB  - The effects of betaxolol on Ca(2+)-induced contractions in saponin-treated
      skinned canine renal arteries were examined. Betaxolol decreased the pCa (
      log[Ca2+] M) 5.8-induced contraction at the same concentrations at which the drug
      relaxed the high K(+)-induced contraction in intact smooth muscles. The pCa
      tension relation was shifted to the right and downward by betaxolol. Betaxolol
      inhibited the increase in Ca(2+)-induced contraction by calmodulin, and this
      effect of betaxolol was observed even at the concentration that had no effect
      when given alone. These results suggest that betaxolol decreases the Ca2+
      sensitivity of the contractile system in skinned canine renal arteries,
      presumably by inhibiting calmodulin-mediated contractions.

PMID- 8866758
TI  - Effect of leukotriene D4 on tracheal mucociliary transport velocity in quails.
AB  - We investigated the effect of leukotriene D4 (LTD4) on tracheal mucociliary
      transport in quails. Topical application of LTD4 (0.2-2 ng) to tracheal mucosa
      dose-dependently increased mucociliary transport velocity (MCTV) in 5 or 10 min
      after application. Forty minutes after application of 2 ng of LTD4, MCTV was
      decreased to about 84% of that in the control group. Both the transient increase
      and the subsequent decrease induced by 2 ng of LTD4 were blocked by ONO-1078
      (Pranlukast: 4-oxo-8-[4-(4-phenylbutoxy)-benzoylamino]-2-(tetrazol-5-yl)- 4H- 1
      benzopyran) (0.03-3 mg/kg, i.m.), a specific leukotriene antagonist. These
      results suggest that LTD4 possesses a biphasic effect on tracheal mucociliary
      transport through leukotriene receptors.

PMID- 8866759
TI  - Effect of terfenadine and KW-4679, a novel antiallergic compound, on action
      potential of guinea pig ventricular myocytes.
AB  - It has been reported that terfenadine caused torsade de pointes ventricular
      arrhythmias. The prolongation of action potential duration (APD) in ventricles is
      considered to be one of the mechanisms of this adverse effect. We examined the
      effect of antiallergic drugs, terfenadine and KW-4679 ((Z)-11-[3
      (dimethylamino)propylidene]-6,11-dihydrodibenz[b, e]oxepin- 2-acetic acid
      hydrochloride), on action potentials in isolated guinea pig ventricular myocytes.
      Terfenadine (30 nM-1 microM) increased APD in a concentration-dependent manner.
      On the other hand, KW-4679 (0.1 microM-100 microM) exerted no significant effects
      on action potential parameters. These results present no evidence that KW-4679
      has the possibility to cause ventricular arrhythmias.

PMID- 8866760
TI  - Therapeutic receptor-blocking concentrations of neuroleptics.
AB  - The therapeutic concentrations of antipsychotic drugs in the patient's plasma
      water or spinal fluid are identical to their blocking potencies in vitro at the
      dopamine D2 receptor, with the exception of clozapine which acts at D4. The
      variation in K values between laboratories stems from the fact that the apparent
      K value for any antipsychotic drug depends on the affinity of the competing
      radioligand for the receptor or the membranes. Clozapine at the D2 receptor has a
      K value of 420 nM using [3H]nemonapride, 180 nM using [3H]spiperone and 82 nM
      using [3H]raclopride. These K values are related to the tissue/buffer partition
      coefficients of the ligands. Extrapolating down to either 1 or 0 partition yields
      the intrinsic K values for the antipsychotic in the absence of any competing
      ligand. The extrapolated or intrinsic K value for clozapine at D4 is 1.3 nM, in
      agreement with the value of 1.1 nM measured directly with [3H]clozapine at D4.
      Clozapine in vivo, however, must compete with endogenous dopamine in the synapse,
      estimated as 50 nM. Thus, the in vivo concentration of clozapine for 75%
      occupation of dopamine D4 receptors can be derived as approximately 14 nM, in
      agreement with the observed value of 12-20 nM in the plasma water or spinal fluid
      in treated patients. In L-DOPA psychosis in Parkinson's disease, the clozapine
      concentration (in the plasma water or spinal fluid) for 75% blockade of dopamine
      D4 receptors may be predicted as approximately 3 nM, in general agreement with
      the value of approximately 1.2 nM in Parkinson patients who have L-DOPA
      psychosis. These considerations provide strong support for the conclusion that
      clozapine primarily targets the D4 receptor in psychosis. Using the same
      considerations for haloperidol, it can be shown that the haloperidol therapeutic
      concentration required for 75% blockade of dopamine D2 receptors in vivo will be
      approximately 2-3 nM, in agreement with the observed value in the spinal fluid or
      plasma water of 1-3 nM.

PMID- 8866762
TI  - Neurocircuitries and neurotransmitter interactions in schizophrenia.
AB  - This review describes an attempt to widen the perspective on schizophrenia and to
      go beyond the dopamine hypothesis. In recent animal experiments corticofugal
      glutamatergic pathways have emerged as powerful regulators of a variety of
      subcortical mechanisms, where the dorsal and ventral striatum appear to play a
      major role in feedback loops controlling a thalamic filter function. These loops
      appear to be important regulators of wakefulness and psychomotor activity. A
      deficient filter function will lead to an overload of sensory input to the
      cerebral cortex and hyperarousal and may ultimately cause breakdown of the
      integrative capacity of the cerebral cortex and psychosis. Both negative and
      positive feedback loops appear to be driven by corticofugal glutamatergic
      pathways, and deficient functions of these loops may cause or contribute to the
      positive and negative symptomatology of schizophrenia, respectively. In addition
      to dopamine and glutamate, several other neurotransmitters, including gamma
      aminobutyric acid, noradrenaline, serotonin and acetylcholine, appear to play an
      important role in psychomotor activity and psychotogenesis. Behavioural and
      biochemical animal models illustrate the interplay between the various
      neurotransmitters in these respects.

PMID- 8866761
TI  - The D3 receptor and its relevance in psychiatry.
AB  - A large fraction of neurotensin neurons in the ventromedial shell subdivision of
      nucleus accumbens express D3 receptors. Blockade of D2/D3 receptors by
      antipsychotic agents paradoxically decreases neurotensin gene expression in these
      neurons whereas it enhances it in other striatal areas expressing the D2
      receptor. This suggests that D2 and D3 receptors mediate opposite actions of
      dopamine. In support of this view low doses of nafadotride, a novel D3 receptor
      preferring antagonist, enhances locomotor activity in rodents, a behavioral
      response opposite to that of current neuroleptics. The action of D3 receptor
      preferring agonists was characterized by the mitogenic response they elicit in
      transfected NG 108-15 cells. Finally, gene expression of the D3 receptor is in
      opposition to that of the D2 receptor, being decreased by denervation and
      unaffected by chronic blockade by neuroleptics.

PMID- 8866763
TI  - Glutamate pharmacology and the treatment of schizophrenia: current status and
      future directions.
AB  - Glutamate-containing neuronal terminals are ubiquitous in the central nervous
      system and their functional importance in mental activity is considerable.
      Therefore, the involvement of this neurotransmitter in the pathology of
      schizophrenia is being studied. Biochemical evidence has suggested that
      glutamatergic transmission may be regionally reduced in schizophrenia, although
      this evidence has never been completely consistent nor fully replicable. More
      striking has been the behavioral effects in humans of the antiglutamatergic drugs
      phencyclidine (PCP) and its congener ketamine. By historical report, PCP produces
      a 'schizophrenia-like' psychosis in normal humans and aggravates the psychosis in
      schizophrenics. More recently, ketamine has been shown to produce a mild
      psychotomimetic effect in normal volunteers, which has some schizophrenia-like
      features. We have studied the effects of ketamine in schizophrenic patients.
      Here, ketamine intensified each patient's specific underlying psychosis, an
      effect not blocked by haloperidol. Moreover, ketamine selectively increased
      cerebral blood flow (CBF) in the anterior cingulate cortex and reduced CBF in
      hippocampus and lingual gyrus. These data may be pertinent to the subject's
      psychosis exacerbation, especially because both cingulate and hippocampus have
      been previously implicated in schizophrenic psychosis. In addition, ketamine
      produced a distinctive dynamic time-course of regional CBF changes in different
      anatomic regions, with immediate (5-10 min) changes in cingulate, but somewhat
      more delayed changes (20-40 min) in the thalamus and cerebellum. Our immediate
      early gene (IEG) time-course data with c-fos and zif268 in rats following PCP
      suggest that a single dose of this antiglutamatergic compound can have an effect
      in some brain areas which lasts beyond 48 h, an effect which is distinct by IEG
      and by region. Together, these data suggest that glutamate-mediated
      neurotransmission has a strong influence in schizophrenia, although the specifics
      of this involvement have yet to be articulated.

PMID- 8866764
TI  - New antipsychotics: the present status.
AB  - Until antipsychotics can be subdivided according to differentiated effects on
      psychic functions (for example on positive/negative symptoms and cognitive
      functions), the best classification seems to be one based upon receptor-binding
      profiles and the side effects that follow. Such a combined pharmacological
      clinical approach appears fruitful to clinicians as well as pharmacologists.
      According to this classification the new antipsychotics can be subdivided into
      three main categories: the relatively pure dopamine antagonists (D2 antagonists,
      including sulpiride and amisulpiride); the dopamine (D2)-serotonin (5-HT2)
      norepinephrine (alpha 1) antagonists (risperidone, ziprazidone and sertindole);
      and the multireceptor antagonists (clozapine, olanzapine and seroquel). Clozapine
      is still the most potent antipsychotic and the least potent at inducing
      extrapyramidal symptoms. New drugs such as olanzapine, seroquel and sertindole
      represent the further development of clozapine's positive qualities, while
      risperidone and ziprasidone are dominated to a greater extent by relatively
      traditional dopamine D2 receptor blockade.

PMID- 8866765
TI  - Aetiology of schizophrenia: an evolutionary theory.
AB  - It is proposed that schizophrenia is a purely genetic condition that arises as a
      component of the variation generated in the speciation of Homo sapiens through
      the evolution of the faculty of language. A critical genetic change on the X and
      Y chromosomes allowed the two hemispheres to develop with a degree of
      independence. Thus Man's particular capacity for communication has evolved by a
      process of increasing hemispheric specialization on the basis of persisting
      diversity for the asymmetry ('right-shift)' factor. Sex differences in age of
      onset of psychosis, premorbid precursors and outcome are accounted for in terms
      of a mean difference between the sexes in cerebral asymmetry. The ultimate cause
      of this difference is the mechanism of sexual selection acting to retain
      different ranges of variation of the gene on the X and Y chromosomes. These
      ranges are expressed in terms of variation in hemispheric specialization and
      psychological function, a boundary of which represents the predisposition of
      psychosis. The hypothesis is developmental in the sense that the relevant gene
      has an influence in development and affects a critical aspect of higher nervous
      system function. But the key evolutionary process of selection of gene variants
      occurs late, by the mechanism of mate choice.

PMID- 8866766
TI  - The psychopathology of schizophrenia: an integrated view on positive symptoms and
      negative symptoms.
AB  - Interest in the distinction between positive and negative symptoms has reached a
      peak in the last decade and has led to research in different fields like
      phenomenology, ethiopathogenesis, treatment, course and outcome. Which symptoms
      are considered positive or negative varies across different authors, although
      there seems to be agreement on a core syndrome. The definition problems can be
      also found in the rating scales used for measuring positive and negative
      symptoms. The positive/negative distinction may represent different
      manifestations of a common underlying process. It also may suggest the existence
      of different pathophysiologies in schizophrenia. Since both positive and negative
      symptoms are frequent in schizophrenia, they are most likely not completely
      independent. The negative/positive syndrome is not sufficient to describe the
      dimensions of the complex phenomenology of schizophrenia. Among others, a
      depressive syndrome needs to be integrated. There is much controversy concerning
      the course of positive and negative symptoms over time. In subacute and chronic
      patients the negative syndrome seems to be more stable than the positive
      syndrome. The differentiation between primary and secondary negative symptoms
      seems to have great relevance to clinical and research aspects. This
      differentiation is an important factor in the interpretation of neuroleptic
      trials on negative symptoms. One way of differentiating between direct and
      indirect drug effects on negative symptoms is to use sophisticated statistical
      procedures, for example path analysis.

PMID- 8866767
TI  - Dosing issues and depot medication in the maintenance treatment of schizophrenia.
AB  - Antipsychotic medication has proved to be of enormous value in the long-term
      treatment of schizophrenia. Maintenance medication has been shown to reduce rates
      of relapse and rehospitalization substantially and to enable patients to benefit
      from psychosocial treatments and vocational rehabilitation. At the same time,
      improving compliance while optimizing the benefits and minimizing the risks
      associated with long-term drug treatment has been a major challenge. Depot
      medications are a valuable part of a maintenance strategy for many patients.
      Considerable data are now available on dose-response relationships with depot
      drugs, improving our ability to use them judiciously.

PMID- 8866768
TI  - Integration of family and drug treatment strategies in the treatment of
      schizophrenia: a selective review.
AB  - It is often asserted that maintenance treatment in schizophrenia requires the
      integration of both medication and psychosocial treatment for maximum benefit. A
      review of research on one psychosocial treatment, psychoeducational family
      treatment, suggests that it provides benefits beyond other psychosocial
      treatments or usual care, but there is no evidence of differences among family
      treatments. Research designs that include comparisons of both medication and
      psychosocial treatment provide the strongest evidence regarding the contribution
      of each to outcome. Two studies have incorporated comparisons of both medication
      and family treatment. In a short-term study that compared family treatment to
      routine care, family treatment had an additive effect to that of medication.
      Goldstein and his colleagues found that subjects who received both a higher dose
      of medication and family treatment had the best outcome. In a longer term study
      that compared two forms of family treatment and three doses of antipsychotic
      medication, Schooler and her colleagues found significant effects of the
      medication condition but no differential effects between the two family
      treatments. Taken together, these studies support a clinical recommendation that
      when family members are available, a psychoeducational family treatment should be
      part of an overall treatment program for schizophrenia.

PMID- 8866770
TI  - The cognitive abnormalities underlying the symptomatology and the disability of
      patients with schizophrenia.
AB  - A variety of cognitive impairments can be observed in patients with
      schizophrenia, including substantial reductions in the intelligence quotient
      (IQ). I propose that these impairments can be best understood in terms of the
      abnormal processes underlying the signs and symptoms manifested by the patient at
      the time of the cognitive assessment. Negative signs such as poverty of speech
      are associated with defects of willed action, while positive symptoms such as
      hallucinations are associated with defects of self-monitoring. Hypotheses about
      the brain systems underlying these processes can be examined using functional
      brain imaging.

PMID- 8866769
TI  - Positron emission tomography studies on D2 dopamine receptor occupancy and plasma
      antipsychotic drug levels in man.
AB  - Positron emission tomography (PET) and the selective radioligand [11C]raclopride
      were used to measure D2 receptor occupancy in several studies in schizophrenic
      patients and healthy subjects. Clinical effects of the treatment were recorded,
      and drug plasma concentrations measured. The hypothesized curvilinear
      relationship between receptor occupancy and drug plasma concentrations was
      supported experimentally. We suggest that there may be a distinct threshold for
      antipsychotic effect at about 70% D2 receptor occupancy, and another threshold
      for extrapyramidal side effects above 80% D2 receptor occupancy. Receptor
      occupancy was high even at low plasma drug concentrations. Our data indicate a
      need to establish dose-response curves for the conventional neuroleptics. Such a
      dose-response relationship might be expected for a much lower dose interval than
      those previously examined.

PMID- 8866771
TI  - Thought disorder, working memory and attention: interrelationships and the
      effects of neuroleptic medications.
AB  - Impairments in attention and vigilance, working memory and organization of speech
      (thought disorder) have been reliably observed in patients with schizophrenia.
      The response in these cognitive parameters to neuroleptic medications can be used
      to sharpen their characterization in neuropsychological terms. In particular, a
      review of the literature suggests that while working memory is relatively
      insensitive to neuroleptics, attention and thought disorder may improve with
      neuroleptic administration. On the basis of the response to typical and atypical
      neuroleptics, attention as deployed in the Continuous Performance Test may
      reflect response readiness rather than actual vigilance. Thought disorder, which
      is often assumed to be the result of impaired discourse planning due to a reduced
      capacity for working memory, does not covary with working memory, and the two
      parameters show different responses to neuroleptic medications. Rather, cognitive
      studies suggest that thought disorder may arise from abnormalities within the
      semantic system itself.

PMID- 8866772
TI  - Motor and mental aspects of extrapyramidal syndromes.
AB  - Neuroleptic-induced extrapyramidal syndromes (EPS) are major limitations to
      effective antipsychotic therapy. There are both motor (objective) and mental
      (subjective) components to EPS, which must be considered in the evaluation and
      differential diagnosis of treatment-related adverse events. In addition to
      causing motor impairment, these syndromes can also produce irritability,
      anxiousness and secondary negative symptoms of slow thinking and emotional
      blunting. The EPS of akathisia, dystonia, and parkinsonism have unique
      characteristics that are influenced by patient, drug and temporal aspects. With
      the advent of new and novel antipsychotic drugs that have low EPS liability,
      patients will have fewer side effects, be less non-compliant and more able to
      benefit from rehabilitation efforts.

PMID- 8866773
TI  - How to distinguish between the neuroleptic-induced deficit syndrome, depression
      and disease-related negative symptoms in schizophrenia.
AB  - A major challenge in the clinical assessment of schizophrenia is the
      differentiation between depressive features, negative symptoms and neuroleptic
      side effects, including the adverse subjective experiences associated with this
      medication. The problems include the degree of symptom overlap, and the lack of
      precise operational definitions, particularly for negative symptoms and the
      putative, neuroleptic-induced deficit syndrome. The diagnostic process is further
      confounded by the need to discriminate between primary negative symptoms as
      persistent, enduring deficits, and social and emotional withdrawal secondary to
      positive symptoms, or related to depressive features or drug effects such as
      sedation and the bradykinesia component of parkinsonism. To distinguish between
      these elements is likely to require careful observation of patients with
      schizophrenia, over time, by trained raters using appropriate rating scales for
      depression and negative symptoms that are sensitive to change. Ratings of
      patients' subjective experiences regarding mood and awareness of behavioural and
      cognitive deficits should also be included. The associations between the
      subjective data and the objective ratings of depression, negative symptoms and
      drug side effects may help with clinical discrimination in these areas of
      dysfunction and with the refinement of their phenomenological descriptions.

PMID- 8866774
TI  - Patients' subjective experiences on antipsychotic medications: implications for
      outcome and quality of life.
AB  - The phenomenon of subjective response to antipsychotic medications in
      schizophrenia was reviewed, focusing on validity, measurement, implications for
      clinical outcome and quality of life. Recommendations were made on improvements
      in research approaches to important factors that may contribute to the genesis of
      this phenomenon. Clinicians should pay attention to the subjective complaints of
      their patients about medications and not ignore them as unreliable. Researchers
      should not dismiss research into subjective experiences as non-scientific,
      because it provides valuable information on recognizing psychopathology and for
      improving the management of patients.

PMID- 8866775
TI  - A self-rating to measure subjective effects of neuroleptic drugs, relationships
      to objective psychopathology, quality of life, compliance and other clinical
      variables.
AB  - The benefit of neuroleptic drugs in the treatment of schizophrenic patients is
      objectively beyond any doubt. However, most patients discontinue their
      neuroleptic drugs within some months. This low compliance might be caused by the
      lack of insight into the disease and the necessity of therapy. Also of major
      importance are adverse effects, not restricted to motor symptoms, but also
      affecting cognition and emotion. They are often too subtle to be detected by
      objective examination, but reported by patients who complain of a reduced quality
      of life with restrictions of emotionality, straight thinking and spontaneity.
      This syndrome, similar to negative symptoms of schizophrenia, has been named
      'pharmacogenic depression' or 'neuroleptic-induced deficit syndrome'. To
      investigate this issue of major clinical relevance, a self-rating scale was
      developed to measure subjective well-being under neuroleptic treatment (SWN).
      First analyses indicate good practicability, reliability, validity and
      sensitivity. Data obtained from 280 remitted schizophrenic patients showed that
      the SWN was significantly correlated to objective psychopathology (Positive and
      Negative Symptom Scale, PANSS; r = -0.35), quality of life (r = 0.60) and other
      self-ratings of mood states [Profile of Mood Scale (POMS), Self-rating Depression
      Scale (SDS), Befindlichkeits Scale (BFS); r = 0.25-0.75]. A repeated application
      after 3 months in 53 patients did not show any change in SWN in those with
      constant neuroleptic medication, but there were marked alterations if the dosage
      or the drug was changed. The SWN in 28 patients treated with clozapine because of
      therapy resistance or major side effects was, despite negative selection,
      significantly better (t = 1.79, p = 0.03) than in 38 patients under classical
      neuroleptics. Moreover, even at dismissal, patients who were non-compliant 4-6
      months later (n = 14) differed significantly (t = 3.21, p = 0.02) in SWN, but not
      in PANSS, from those who remained compliant (n = 34). These data indicate that
      the SWN is a useful tool for investigating a hitherto neglected
      psychopathological dimension. Subjective effects of neuroleptics are measurable,
      affect patients' quality of life and should be considered more thoroughly in
      clinical routine as well as in clinical trials of potential neuroleptic drugs.

PMID- 8866776
TI  - Review. David Oppenheimer Memorial Lecture 1995: Some neuropathological aspects
      of Alzheimer's disease and its relevance to other disciplines.
AB  - Recent studies of diffuse A beta plaques point to the neurons as a source of A
      beta in diffuse plaques. The neuritic (primitive and classical) plaques appear to
      be the product of microglia and the myocytes are the source of amyloid deposits
      in the meningeal and cortical vessels. Dyshoric angiopathy is associated with
      deposits of amyloid by perivascular cells. Fibrillization of the neuron-derived
      diffuse, thioflavine-negative or benign plaques is poor or undetectable by
      current morphological methods including ultrastructural immunocytochemistry. It
      appears that fibrillization depends on the length of the A beta peptides and on
      the presence of amyloid-associated proteins. Four genes are now tightly linked
      with Alzheimer's disease (AD) and they are located on chromosomes 21, 19, 14 and
      1. Therefore, AD should be considered a polyaetiological disease or syndrome.
      There are currently five transgenic mouse models overexpressing beta-APP. There
      is also a myocyte tissue culture model in which both soluble and fibrillized A
      beta are found. The relationship between A beta and neurofibrillary pathology is
      not clear and the current cascade hypothesis proposing that A beta pathology
      drives the formulation of neurofibrillary tangles is being questioned. There is
      growing evidence that it is not the A beta hypothesis, but the co-existing A beta
      neurofibrillary tangle pathology hypothesis which will be the basis for AD
      neuropathology.

PMID- 8866777
TI  - Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer.
AB  - The chronic neurological sequelae of boxing are well described, but there have
      been few neuropathological studies of boxers dying early in their career. We
      report the case of a 23-year-old boxer, whose brain showed neurofibrillary
      tangles in all neocortical areas, but remarkable sparing of medial temporal lobe
      structures. These tangles, assumed to be the result of repetitive head injury,
      were the only detectable abnormality: none of the other changes previously
      described in the brains of retired boxers were seen. The distribution and
      features of the neuropathological findings in this case suggest that the
      mechanism of tangle formation induced by repetitive head trauma may be different
      from that in Alzheimer's disease.

PMID- 8866778
TI  - Patterns of glial cell activity in fronto-temporal dementia (lobar atrophy).
AB  - Fronto-temporal dementia is a clinical syndrome with a number of pathological
      substrates, including frontal lobe degeneration, Pick's disease, and motor neuron
      disease with dementia; it also includes patients with a primary progressive
      language disorder. Twenty-four brains were examined, using immunohistochemistry
      for glial fibrillary acidic protein (GFAP) and ferritin. Five cases of fronto
      temporal dementia with a Pick's disease type of histology showed marked cortical
      gliosis with striking microglial activity in both grey and white matter. In seven
      cases of frontal lobe degeneration, there was little gliosis and microglial
      activity was confined largely to the white matter; two of the seven cases of
      progressive language disorder showed similar changes to frontal lobe
      degeneration. Five cases of motor neuron disease with dementia showed both
      astrocytic and microglial activity within the white matter. We suggest that cases
      of fronto-temporal dementia due to Pick type histology may result from a process
      which primarily involves grey matter, whereas cases of frontal lobe degeneration
      might represent a disorder of white matter.

PMID- 8866779
TI  - Evidence for neuronal apoptosis in pontosubicular neuron necrosis.
AB  - Pontosubicular neuron necrosis (PSN) is characterized by acute neuronal death in
      the subiculum and the pons occurring in a circumscribed perinatal period. The
      morphological changes in PSN are quite similar to those described during
      apoptosis, a form of programmed cell death. Morphological re-evaluation of the
      lesions by light and electron microscopy revealed the typical changes of
      apoptosis with condensed basophilic nuclei and the formation of apoptotic bodies.
      By analysing DNA fragmentation in situ with a recently established technique, we
      were able to show that neuronal death in PSN is apoptotic. The demonstration of
      DNA fragmentation by the in situ tailing technique was reliable in the human
      autopsy material used in this study and was only slightly affected by autolysis
      or formalin fixation. The subiculum and the pons are shown to be susceptible to
      apoptosis at different times during development. PSN thus provides a model in
      which the process of nerve cell apoptosis in the developing human central nervous
      system can be studied.

PMID- 8866780
TI  - Ultrastructural localization of adhalin, alpha-dystroglycan and merosin in normal
      and dystrophic muscle.
AB  - Adhalin and alpha-dystroglycan are two components of a complex of proteins that,
      in conjunction with dystrophin, provide a link between the subsarcolemmal
      cytoskeleton and the basal lamina of the extracellular matrix of skeletal muscle.
      In the absence of dystrophin, in Duchenne muscular dystrophy (DMD) and the mdx
      mouse, levels of adhalin, alpha-dystroglycan and other components of the complex,
      are severely reduced, and it has been speculated that this might be an important
      factor in precipitating myofibre necrosis. However, there is, as yet, little
      information on how these proteins interact structurally or functionally. From
      biochemical data it might be predicted that adhalin and alpha-dystroglycan are
      positioned more peripherally in the muscle cell than dystrophin and more proximal
      than merosin. Using single and double immunogold labelling we here show that
      adhalin is localized to the plasma membrane with the majority of the gold probe
      particles situated on the membrane's outer face, while alpha-dystroglycan
      labelling is seen on material which projects from the outer face and which, in
      places, forms strands that stretch to the basal lamina. When double labelling of
      laminin and alpha-dystroglycan is carried out, laminin is localized to the
      proximal face of the basal lamina, facing the alpha-dystroglycan. In DMD the
      labelling of adhalin and alpha-dystroglycan is severely reduced quantitatively
      (although the vestige that remains is positioned normally) but merosin is
      expressed normally, showing that its incorporation is independent of that of
      dystrophin and its associated proteins.

PMID- 8866781
TI  - Acquired multifocal myofibrillar disruption selective of type II fibres.
AB  - We report three cases of patients who complained of myalgia showing histological
      features similar to tubular aggregates in their muscle biopsies. All had an
      elevated erythrocyte sedimentation rate without any evidence of infectious or
      autoimmune disease. On electron microscopy, small areas of myofibrillar
      degeneration, selectively in type II fibres, were found in all patients, but no
      tubular aggregates were seen. Although the pathogenesis of these lesions is
      unclear, it does seem that this condition is acquired and transient.

PMID- 8866782
TI  - A comparison of leucocyte responses to heat-killed bacillus Calmette-Guerin in
      different CNS compartments.
AB  - We have previously shown that heat-killed bacillus Calmette-Guerin (BCG) injected
      into the CNS parenchyma does not produce a typical delayed-type hypersensitivity
      (DTH) response [23]. In this paper we have compared the initial leucocyte
      response in the CNS parenchyma, ventricles and skin to gain insight into the
      mechanisms by which the DTH response in the CNS might be controlled. We have
      found that 10(5) organisms of heat-killed BCG injected into either the CNS
      parenchyma or the lateral ventricles produced a rapid neutrophil response at the
      site of the injection, which was comparable with that in the skin. The neutrophil
      response resolved within the first week. Unlike the neutrophil response, the
      mononuclear phagocyte response in the CNS parenchyma was much smaller than that
      seen in the ventricles and the skin and it resolved within 4 weeks. Furthermore,
      the myelomonocytic response in the CNS parenchyma failed to clear the BCG. The
      acute inflammatory response in the choroid plexus/ventricles and skin developed
      with a similar time-course into a typical DTH response. After the first week,
      lesions at these two sites were composed predominantly of T-cells and
      macrophages. DTH lesions were still detected at both sites after 6 weeks. The
      failure of the immune system to recognize foreign antigens sequestrated in the
      CNS parenchyma may have significant implications especially in studies of
      inflammatory responses in the CNS of unknown origin.

PMID- 8866783
TI  - mRNA for NGF and p75 in the central nervous system of rats affected by
      experimental allergic encephalomyelitis.
AB  - In this study we measured the concentration of nerve growth factor (NGF) and the
      expression of NGF and the low affinity NGF-receptor (NGF-r) mRNA in the central
      nervous system (CNS) of rats affected by experimental allergic encephalomyelitis
      (EAE) during the acute phase of the disease. Significant levels of NGF protein
      were found in thalamus and cortex on day 13 post-immunization. Molecular analysis
      of the NGF gene expression and of its NGF-r revealed that they were enhanced in
      several regions of the CNS of EAE rats when compared with untreated animals.
      These results suggest a functional link between local NGF synthesis and this
      autoimmune inflammatory disease.

PMID- 8866785
TI  - Lectin histochemistry, ploidy level and proliferation indices in meningioma
      subtypes.
AB  - The glycohistochemical expression of binding sites for eight lectins is
      characterized in a series of 15 meningothelial, 10 fibroblastic and 15
      transitional meningiomas. The correlation between lectin staining and either the
      proliferation index or ploidy level has also been investigated. The data show
      that the cytochemical binding of some lectins is of value in distinguishing
      between the different meningioma subgroups. For example, fibroblastic meningiomas
      express significantly higher amounts of wheat germ agglutinin (WGA) and Ulex
      europaeus agglutinin (UEA-I) than the meningothelial sub-type. Diploid tumours
      express a higher glycine maximus (SBA), Arachis hypogaea (PNA) and Phaseolus
      vulgaris leukoagglutinin (PHA-L) binding than aneuploid tumours. These
      differences are probably due to the modification of post-transcriptional
      glycosylation events linked to tumour ageing. The data also reveal that the
      increased binding of PHA-L is inversely correlated with the proliferation indices
      of the tumours.

PMID- 8866784
TI  - Cytoskeletal changes in cultured human fibroblasts following exposure to 2,5
      hexanedione.
AB  - In the present study, the effects of the 2,5-hexanedione (HD) on the various
      cytoskeletal components of human eukaryotic cells were investigated. Primary
      cultures of human fibroblasts from three healthy donors were exposed to 2.8 mM HD
      for 14 days; unexposed cultures were used as controls. At different time
      intervals, cells were counted and the growth curves compared. After 14 days of
      treatment, the cultures were processed for immunoblotting, immunocytochemistry
      and ultrastructural studies. As compared to controls, morphological abnormalities
      induced by HD consisted of modification of the cell shape, formation of tangles
      composed by 10 nm filaments and cytoplasmic segregation of microtubules and
      membrane-bound organelles. By immunocytochemistry, the tangles of cytoplasmic
      filaments were stained by an antibody specific for vimentin. By immunoblotting,
      the anti-vimentin antibody recognized only bands of 50-60 kDa. Comparison of
      growth curves between treated and control fibroblasts clearly revealed an
      interference of HD with the cell cycle. The present results demonstrate that the
      cytotoxicity of HD is not restricted to intermediate filaments, but affects other
      cytoskeletal components, such as microtubules, as suggested by the impairment of
      cell division cycle.

PMID- 8866786
TI  - Nerve and muscle biopsy in a case of hereditary motor and sensory neuropathy type
      III with basal lamina onion bulbs.
AB  - A girl presented at age 8 months with generalized hypotonia and areflexia. The
      parents were unrelated and without symptoms. At the age of 2 years and 10 months
      she was able to stand and walk with support. Intellectual development was normal.
      The mean fibre size in the lateral vastus muscle was normal, the variability was
      slightly increased. Type I and II fibres tended to be aggregated, but there was
      no type grouping. Motor and sensory nerve conduction velocities were less than 6
      m/s. The sural nerve lacked myelin sheaths, and large non-myelinated axons were
      surrounded by concentric layers ('onion bulbs') of basal lamina material. The
      disease was classified as 'autosomal recessive hereditary motor and sensory
      neuropathy type III(HMSN (III) with basal lamina onion bulbs'. The muscle biopsy
      findings suggest that congenital amyelination or hypomyelination does not
      necessarily result in neurogenic atrophy.

PMID- 8866787
TI  - Letter to the editor.

PMID- 8866788
TI  - Increased cAMP and cAMP-dependent protein kinase activity mediate anti-CD2
      induced suppression of anti-CD3-driven interleukin-2 production and CD25
      expression.
AB  - Anti-CD2 monoclonal antibody (mAb) can act synergistically with anti-CD3 to
      produce tolerance and diminish the anti-CD3-induced cytokine syndrome. Since
      interleukin(IL)-2 production and IL-2 receptor (IL-2R; CD25) expression are
      important determinants of CD3-driven T cell activation, the effects of anti-CD2
      on anti-CD3-induced CD25 expression and IL-2 production were analyzed and related
      mechanistically to CD2-stimulated cAMP signaling with an in vitro model of T cell
      activation. The anti-CD2 mAb, 12-15, alone had no effect on splenic T cell CD25
      expression and IL-2 production, while the anti-CD3 mAb, 145-2C11, caused
      significant increases in both CD25 expression and IL-2 production. The addition
      of anti-CD2 inhibited anti-CD3-induced increases in CD25 and IL-2. The inhibitory
      signal delivered by anti-CD2 was effective in many forms of T cell activation,
      since other stimuli which increased CD25, such as concanavalin A,
      phytohemagglutinin, and Staphylococcal enterotoxin B (SEB), could also be
      inhibited by anti-CD2. The inhibitory effect of anti-CD2 on CD25 could not be
      reversed by high doses of supplemental IL-2 added to the culture. Anti-CD2
      increased cytoplasmic cAMP in a dose- and time-dependent manner. Reagents that
      increased cytoplasmic cAMP such as forskolin, cholera toxin, and 3'-isobutyl-1
      methylxanthine could mimic the inhibitory effect of anti-CD2 on anti-CD3-driven
      CD25 expression. Anti-CD2 also increased the activity of cAMP-dependent protein
      kinase (PKA). H8, a PKA antagonist, blocked the inhibitory effect of anti-CD2 on
      CD25 expression, further confirming the role of PKA in CD2-induced negative
      signaling. The use of paired agonists to PKA demonstrated that a type I PKA was
      the preferential enzyme isoform stimulated by CD2 ligation. These findings show
      that increased cAMP and PKA activity mediate anti-CD2-induced suppression of anti
      CD3-driven IL-2 production and CD25 expression, and provide mechanisms for anti
      CD2-induced immunosuppression and inhibition of the cytokine syndrome associated
      with anti-CD3 treatment.

PMID- 8866789
TI  - Primary central nervous system lymphoma following transfer of human peripheral
      blood lymphocytes into SCID mice.
AB  - Severe combined immunodeficiency (SCID) mice are genetically deficient in both B
      and T cells. To study immune-mediated phenomena in the CNS, myelin basic protein
      reactive T cell clones, admixed with peripheral blood lymphocytes as a source of
      antigen-presenting cells, derived from a healthy human donor, were injected
      intracerebrally (IC) into 10 SCID mice. One mouse developed quadriplegia 2 months
      after the last injection. Autopsy revealed marked meningeal and parenchymal
      infiltration by large cell lymphoma. There was no evidence of lymphoma outside of
      the CNS. The majority of the tumor cells were positive for L26 (a human pan B
      cell marker), with some cells positive for UCHL-1 (a human pan T cell marker).
      The majority of the tumor cells were also positive for Epstein-Barr virus (EBV)
      genome by in situ hybridization. Thus, primary CNS, EBV-positive B cell lymphoma
      can be produced in SCID mice by IC injection of nontransformed human peripheral
      blood lymphocytes. This phenomenon can be used as a model system for the study of
      primary CNS lymphomas under immunodeficiency conditions.

PMID- 8866790
TI  - Expression of Bcl-2 protein in human laryngeal keratoses.
AB  - Strong Bcl-2 immunostaining was detected in 2 of 21 samples of human laryngeal
      keratoses, one of which contained neither p53 gene mutation nor human
      papillomavirus sequences nor significant levels of p53 protein. The other 19
      samples including 6 cases with moderate or strong p53 staining were Bcl-2
      unreactive or had minimal Bcl-2 reactivity similar to that observed in normal
      samples. Minimal Bcl-2 staining in 5 samples with moderate or severe dysplasia
      was only seen in the adjacent nondysplastic area. Our study shows that (1) some
      laryngeal keratoses strongly express Bcl-2 protein, (2) Bcl-2 expression does not
      appear to be dependent on p53, and (3) moderate or severe dysplasias may occur
      despite a decline in Bcl-2 expression.

PMID- 8866791
TI  - Overexpression of human glutathione S-transferase pi protects NIH 3T3 cells
      against (+/-)anti BPDE cytotoxicity but not tumor formation.
AB  - In order to explore the protective function of human glutathione S-transferase pi
      (GST-pi) in vitro and in vivo, transfected NIH 3T3 clones were examined in
      cytotoxicity assays using the carcinogen (+/-)anti-benzo(a)pyrene 7,8-diol-9,10
      epoxide (BPDE) or inoculated into nude mice and treated with the carcinogen
      benzo(a)pyrene (BP) to induce tumor formation. The human GST-pi cDNA under the
      control of the murine alpha 2(I)collagen promoter was transfected into NIH 3T3
      cells and G418 resistant clones were analyzed by Southern, northern, western, and
      two-dimensional analysis. Clone A2 stably expressed human GST-pi and has 2.5-fold
      greater activity toward the substrate 1-chloro-2,4-dinitrobenzene and a 1.7-fold
      increase in LD50 for BPDE in vitro when compared to control-transfected clone G3.
      This increase in protection, however, did not prevent the formation of BP-induced
      tumors in vivo.

PMID- 8866792
TI  - Effects of cytokines on the expression of cell adhesion molecules by cultured
      human omental mesothelial cells.
AB  - Cultured mesothelial cells (HOMES) are very responsive to the proinflammatory
      cytokines, interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha). E
      selectin, ICAM-1 and VCAM-1 are known to play an important role, because they are
      presented by diverse cell types, for example endothelial cells (ECs), and
      interact with co-responding ligands on white blood cell membranes. In this study,
      the expression of ICAM-1, VCAM-1, E-selectin as well as PECAM-1 on cultured HOMES
      was studied over 5, 24, 48 and 72 h exposure to IL-1 beta, interferon-gamma and
      TNF-alpha. In previous studies we have shown that IL-1 beta and TNF-alpha
      increase the expression of ICAM-1, E-selectin and VCAM-1 on the cytoplasmatic
      membranes of HUVECs, HSVECs and HAFECs (ECs from human umbilical vein, saphenous
      vein and femoral artery, respectively). Using a comparative quantitative cell
      enzyme immunoassay, we found that expression of the adhesion molecules ICAM-1 and
      VCAM-1 was significantly increased on HOMES in a dose- and time-dependent manner,
      compared to nonstimulated cells. Thus, ICAM-1 increased dramatically after 5 h
      incubation with TNF-alpha. Values of about 450% of the control level were
      measured. VCAM-1 was similarly stimulated after 24 h incubation with the same
      cytokine, although its level of expression was significantly lower than that of
      ICAM-1. In contrast to findings in the literature, VCAM-1 was not found to be
      expressed constitutively. E-selectin was neither constitutively expressed nor
      markedly inducible on HOMES. Only weak expression was found after 24 h incubation
      with high-dose IL-1 beta. PECAM-1 was expressed constitutively, as became evident
      in antibody dilution studies. These data indicate that HOMES respond to
      inflammatory stimuli, in some ways in a similar fashion to vascular endothelial
      cells, but also show a specific pattern of antigen presentation. The results are
      important for a better understanding of inflammatory processes in serous
      cavities. The data are also relevant for the improvement of antithrombogenous
      surfaces of the lumina of vascular prostheses by cell seeding.

PMID- 8866793
TI  - Mineral fibers induce apoptosis in Syrian hamster embryo fibroblasts.
AB  - It is known that asbestos and other mineral fibers induce lung cancer and
      mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis
      still remain to be elucidated. Previous studies, including our own, have shown
      that asbestos causes specific mitotic disturbances, micronucleus formation and
      typical changes in chromatin structure resembling those of apoptosis. This effect
      has been considered as programmed cell death removing damaged or pre-cancerous
      cells. We investigated the induction of apoptosis by asbestos (amosite,
      crocidolite, chrysotile) and ceramic fibers. The typical ladder pattern of DNA
      fragments was identified by means of gel electrophoresis, the intracellular
      calcium concentration was measured and flow cytometry analyses were carried out
      to determine the percentage of apoptotic cells. The different fibers showed
      different potencies for the induction of apoptosis in Syrian hamster embryo (SHE)
      cells. Depending on the type of fiber applied 3-33% of cells underwent apoptosis.
      Chrysotile proved to be the most potent inducer of apoptosis compared to the
      other fibers. In addition, an increase intracellular calcium level was observed
      in apoptotic SHE cells. Chrysotile induced apoptosis after a considerably longer
      exposure time (66-72 h) than cisplatin (24 h). In view of these findings we
      hypothesize that chrysotile induces apoptosis resulting from long-term changes in
      intracellular regulation pathways.

PMID- 8866794
TI  - Primary cilia in normal and pathological tissues.
AB  - The medical literature in pathology contains a surprising number of anecdotal
      reports of primary cilia, with authors often expressing some incredulity at
      finding such organelles. In this update of an earlier review, I will argue that
      primary cilia should by now be regarded as regular cell organelles, not some form
      of atypical response to unusual circumstances. In all situations in which their
      presence is essential, they unquestionably act as sensory transducers. Detection
      by electron microscopy has been the most reliable means until recently, but is
      time-consuming and slow for any systematic investigation or experimental
      approach. Immunostaining with an antibody direct against detyrosinated tubulin is
      rapidly changing the situation, and we can now detect their presence, frequency,
      disposition and overall characteristics relatively quickly, allowing better
      statistical analysis and correlations in abnormal physiological and pathological
      conditions. To be useful and meaningful, comparative studies need a reliable
      database of information about primary cilia under 'normal' circumstances. It is
      hoped that such work will in itself give much further insight into the general
      significance of these organelles, especially combined with the more experimental
      approaches that can now be adopted in the study of their development and
      function, which looks increasingly promising with the new technological
      improvements.

PMID- 8866795
TI  - Pathogenesis of otitis media: role of eustachian tube.

PMID- 8866796
TI  - Predictors for a positive blood culture in African children with pneumonia.
AB  - BACKGROUND: Blood culture isolation rates for children with pneumonia are
      generally low. Therefore it would be helpful if epidemiologic studies could
      identify children who have a higher than average chance of yielding a positive
      culture. METHODS: Simple clinical and laboratory predictors of a positive blood
      culture were investigated in 1222 children younger than 5 years of age with
      pneumonia who presented at rural dispensaries in The Gambia, West Africa.
      RESULTS: A high temperature (chi square for linear trend, 24.1; P < 0.0001), a
      rapid respiratory rate (chi square for linear trend, 6.33; P = 0.010),
      dehydration (odds ratio, 2.33; P < 0.001), nasal flaring (odds ratio, 2.06; P =
      0.001), grunting (odds ratio, 4.01; P < 0.001), dullness to percussion (odds
      ratio, 2.31; P < 0.001), bronchial breathing (odds ratio, 2.61; P < 0.001) and
      diminished breath sounds (odds ratio, 2.07; P < 0.001) were positive predictors
      for a positive blood culture. Wheezing (odds ratio, 0.16; P < 0.001) and malaria
      parasitemia (odds ratio, 0.26; P = 0.008) were negative predictors. A combination
      of these findings were used to assess how the number of cultures taken might be
      reduced without substantially reducing the yield of positive cultures. For
      example it was found that exclusion of children with a temperature of < 38.0
      degrees C and/or a respiratory rate of < 50/min and/or wheezing would have
      reduced the number of cultures taken by 55.6% but would have led to a loss of
      only 31.3% of positive cultures. CONCLUSION: Careful selection of children
      investigated by blood culture could help to reduce the work required during the
      preparations for and conduct of pneumococcal vaccine trials.

PMID- 8866797
TI  - Cerebrospinal fluid values in the term neonate.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) values in the noninfected neonate are not
      well-delineated. Studies analyzing these values are inconsistent in the criteria
      used to define the noninfected population. The purpose of our study was to
      examine CSF values in neonates in the first 30 days of life in whom infection was
      more thoroughly excluded than in previous reports. Stringent inclusion criteria
      defined the noninfected population, and the recently available polymerase chain
      reaction (PCR) for enteroviruses was used in addition to cultures to help exclude
      viral disease. Results were also stratified by age in weeks to evaluate for any
      variability that occurs in CSF values during the first month of life. METHODS:
      Neonates were selected from subjects enrolled in two studies on aseptic
      meningitis. Noninfected infants were identified by the following criteria: (1)
      atraumatic lumbar puncture (< or = 1000 red blood cells/mm3); (2) no antibiotic
      therapy before lumbar puncture; (3) sterile blood, CSF and urine bacterial
      cultures; (4) negative CSF viral culture; and (5) negative CSF PCR for
      enteroviruses. RESULTS: The mean +/- SD total CSF white blood cell count for 108
      noninfected neonates was 7.3 +/- 14/mm3 (95% confidence interval 6.6 to 8.0/mm3)
      with a median of 4/mm3 and a range of 0 to 130/mm3. There were no significant
      differences in the mean CSF white blood cell counts among age categories.
      CONCLUSIONS: The application of stringent inclusion criteria and the use of the
      PCR yielded a population of infants that better represents the noninfected
      neonate than earlier reports. These values can be used for reference in
      evaluating the febrile or ill neonate.

PMID- 8866798
TI  - Is urine culture necessary to rule out urinary tract infection in young febrile
      children?
AB  - OBJECTIVE: To determine whether the absence of pyuria on the enhanced urinalysis
      can be used to eliminate the diagnosis of urinary tract infection, avoiding the
      need for urine culture and sparing large health care expenditures. DESIGN:
      Results of an enhanced urinalysis (hemocytometer counts and interpretation of
      Gram-stained smears) performed on uncentrifuged urine specimens obtained by
      catheter were correlated with urine cultures in young febrile children at the
      Children's Hospital of Pittsburgh Emergency Department. In a group of 4253
      children (95% febrile) less than 2 years of age, pyuria was defined as > or = 10
      white blood cells/mm3, bacteriuria as any bacteria on any of 10 oil immersion
      fields in a Gram-stained smear and a positive culture as > or = 50,000 colony
      forming units/ml. A subgroup of 153 children with their first diagnosed urinary
      tract infection were enrolled in a separate treatment trial, acute phase
      reactants (peripheral white blood cell count, erythrocyte sedimentation rate and
      C-reactive protein) were obtained and 99Tc-dimercaptosuccinic acid renal scans
      were performed. RESULTS: The presence of either pyuria or bacteriuria and the
      presence of both pyuria and bacteriuria have the highest sensitivity (95%) and
      positive predictive value (85%), respectively, for identifying positive urine
      cultures. Because a white blood cell count in a hemocytometer is the technically
      simpler component of the enhanced urinalysis, we chose to analyze the false
      negative results and achievable cost savings of using pyuria alone as the sole
      criterion for omitting urine cultures. If in this study urine cultures had been
      performed only on specimens from children who had pyuria or were managed
      presumptively with antibiotics, cultures of 2600 (61%) specimens would have been
      avoided. Twenty-two of 212 patients with positive urine cultures would not have
      been identified initially. However, based on interpretation of acute phase
      reactants, initial 99Tc-dimercaptosuccinic acid scan results, response to
      management and incidence of renal scarring 6 months later, 14 of the 22 patients
      most likely had asymptomatic bacteriuria and fever from another cause. The
      remaining 8 patients probably had early urinary tract infection. CONCLUSIONS: The
      analysis of urine samples obtained by catheter for the presence of significant
      pyuria (> or = 10 white blood cells/mm3) can be used to guide decisions regarding
      the need for urine culture in young febrile children.

PMID- 8866799
TI  - Cytomegalovirus infection in human immunodeficiency virus type 1-infected
      children.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a frequent opportunistic infection in human
      immunodeficiency virus type 1 (HIV-1)-infected children. The interactions of CMV
      and HIV-1 in coinfected children are not well-characterized. OBJECTIVE: To
      evaluate the prevalence of asymptomatic CMV infection and symptomatic CMV disease
      and to assess the influence of CMV on clinical and laboratory markers of HIV
      disease progression in CMV-coinfected children. METHODS: Serial urine CMV
      cultures were performed on 500 children (131 HIV-1-infected (HIV+), 129
      seroreverters born to HIV-infected mothers, and 240 HIV-uninfected (HIV-)). The
      clinical, immunologic and virologic data of 131 HIV+ children were analyzed.
      RESULTS: CMV was recovered in 40 of 131 HIV+ (31%), 22 of 129 seroreverters (17%)
      and 30 of 240 HIV- (13%) children. Of the 40 HIV+ children with CMV coinfection,
      7 developed symptomatic CMV disease (17.5%) including chorioretinitis (3),
      colitis (2) and pneumonitis (2). The HIV+ children with symptomatic CMV disease
      had significantly lower mean CD4+ T lymphocyte proportions (17% vs. 26%; age
      adjusted P = 0.013) and greater HIV p24 antigen concentrations (329 pg/ml vs. 57
      pg/ml; age-adjusted P = 0.13) than HIV+ children with asymptomatic CMV infection.
      In a subset of children coinfected with CMV before 6 months of age (n = 11), 5
      (45%) developed symptomatic CMV disease, and 4 of these 5 children died within 10
      months of diagnosis of CMV disease. At the time of the first positive CMV culture
      in these children, mean CD4+ T lymphocyte proportions did not differ according to
      the presence or absence of CMV-related symptoms (symptomatic CMV+, 21% vs.
      asymptomatic CMV = 38%; P = 0.14). In HIV+ children with symptomatic CMV disease,
      p24 antigen concentrations were greater than in those with asymptomatic CMV
      infection (461 vs. 190 pg/ml, P = 0.06). CONCLUSIONS: Symptomatic CMV disease
      occurred in young CMV-coinfected children with low CD4+ lymphocytes and elevated
      HIV p24 antigen concentrations. Whether progressive immunodeficiency allows the
      emergence of CMV disease or CMV infection causes more rapidly progressive HIV-1
      disease or whether there is a more complex relationship remains to be determined.

PMID- 8866800
TI  - Syncytium-inhibiting and neutralizing activity in maternal sera fail to prevent
      vertical transmission of human immunodeficiency virus type 1.
AB  - OBJECTIVES: To measure the prevalence and titers of syncytium-inhibiting (SI) and
      neutralizing (Nt) antibodies to HIV-1 in mothers' blood close to the time of
      delivery and to correlate such findings with the infection status of their
      offspring. METHODS: We analyzed serum specimens from a convenience sample of 22
      HIV-infected mothers. The HIV-1 infection status of their children was
      determined. Forty-five percent of the women transmitted and 55% did not transmit
      infection to their offspring. Cord blood samples from offspring of the mothers
      were also studied. We measured maternal SI antibody titers against cells infected
      with HIV-1/SB, a strain isolated from a transmitting mother in New Haven, as well
      as cells infected with the more prevalent MN strain of HIV-1. We compared SI
      antibody titers to the SB strain in 11 matched maternal and cord blood samples.
      Nt antibody titers to HIV-1/SB were also measured in 20 maternal sera. RESULTS:
      Using the SB and MN strains of HIV-1, we found no difference in the prevalence or
      titer of SI antibody in the sera of transmitting and nontransmitting mothers.
      Only 35% of samples were concordant for presence or absence of SI antibody to the
      two strains. Furthermore the presence or absence of SI antibody in cord blood did
      not correlate with virus transmission. Both the frequency and titer of Nt
      antibody to HIV-1/SB were higher in the sera of mothers who transmitted infection
      when compared to those who did not. Only one-half of maternal blood samples were
      concordant for either the presence or absence of SI and Nt antibodies.
      CONCLUSIONS: We could not demonstrate a correlation between the presence of two
      types of functional antibodies (i.e. SI and Nt) to HIV-1 in the sera of pregnant
      women and vertical transmission. Efforts to induce or to increase such antibodies
      in infected mothers by immunization with vaccines or hyperimmune globulins may
      not alter the risk of vertical transmission.

PMID- 8866801
TI  - Disease patterns and survival after acquired immunodeficiency syndrome diagnosis
      in human immunodeficiency virus-infected children.
AB  - BACKGROUND: The clinical manifestations of HIV infection in children involve a
      broad spectrum of conditions ranging from mild symptoms to AIDS. Knowledge of the
      disease and survival patterns of these children are needed to plan for future
      needs and develop baseline information to evaluate newer prophylactic or
      therapeutic management options. OBJECTIVES: To identify AIDS-defining conditions
      and estimate post-AIDS diagnosis survival among HIV-infected children. METHODS:
      Disease patterns and survival after the diagnosis of AIDS-defining conditions
      were studied in 126 children who were identified through a multisite university
      based active surveillance system in California from January, 1989, through
      August, 1993. Hospital medical records were periodically reviewed and data were
      abstracted onto standardized forms designed for pediatric HIV surveillance. We
      determined the length of survival between AIDS diagnosis and death and evaluated
      the impact of disease patterns on survival using Kaplan-Meier's product-limit
      method and Cox proportional hazards regression. RESULTS: The median age at
      diagnosis was 13 months for children with perinatally acquired infection and
      101.5 months for children infected through other routes of transmission.
      Pneumocystis carinii pneumonia and lymphoid interstitial pneumonia were the most
      common AIDS-defining conditions among perinatal cases, whereas the disease
      patterns observed among nonperinatal cases were more varied. The median
      postdiagnosis survival for the cohort was 26 months. CONCLUSIONS: Survival time
      did not differ significantly by race/ethnicity, sex or route of transmission.
      Respiratory candidiasis and wasting syndrome had significant negative impact on
      survival but P. carinii pneumonia was not associated with shorter survival.
      Zidovudine or other antiviral therapies was associated with increased survival.

PMID- 8866802
TI  - Evaluation of nasopharyngeal cultures for bacteriologic assessment of acute
      otitis media in children.
AB  - BACKGROUND: The recent emergence of penicillin-resistant Streptococcus
      pneumoniae, particularly in acute otitis media (AOM), has increased interest in
      the development of noninvasive procedures that might help to predict the
      bacterial etiology of this condition. We conducted an open multicenter study to
      evaluate the predictive value of the nasopharyngeal (NP) sampling in children
      with AOM by comparing the bacteriologic results of NP cultures with those of pus
      collected by myringotomy in the same patients. METHODS: The NP secretions and the
      pus obtained by myringotomy were collected concomitantly in 354 children younger
      than 6 years of age with clinical signs of AOM. The clinical usefulness of NP
      culture was determined by calculating its sensitivity and specificity, and
      especially its positive and negative predictive values for the three main
      pathogens responsible for AOM, Haemophilus influenzae, S. pneumoniae and
      Moraxella catarrhalis. RESULTS: A positive NP culture was found to have little
      predictive value for H. influenzae (52%), S. pneumoniae (43%) and M. catarrhalis
      (19%). In contrast the negative predictive value of NP cultures was much greater
      and was accompanied by negative middle ear fluid cultures in more than 95% of
      children, especially for S. pneumoniae. Furthermore the incidence of beta
      lactamase-producing strains of H. influenzae at both sampling sites was similar
      (30 and 35%, respectively), as was the incidence of penicillin-resistant S.
      pneumoniae (50 and 54%). CONCLUSION: It appears that the correlation between
      results of NP and middle ear fluid cultures in children with AOM is too weak to
      allow NP culture to be recommended for the bacteriologic documentation of this
      disease. However, these results should not overshadow the considerable
      epidemiologic value of NP cultures, particularly with reference to the monitoring
      of pneumonococcal susceptibility in children. The collection of NP cultures
      should therefore be promoted for their collective epidemiologic value.

PMID- 8866803
TI  - Pilot trial of a pentavalent pneumococcal polysaccharide/protein conjugate
      vaccine in Gambian infants.
AB  - BACKGROUND: Invasive pneumococcal disease is a major cause of mortality and
      morbidity in young children in developing countries. Pneumococcal
      polysaccharide/protein conjugate vaccines, which are likely to be immunogenic in
      the very young, offer a potential way for preventing these infections. Therefore
      a pilot safety and immunogenicity study of a five-valent conjugate vaccine has
      been undertaken in an area of rural Africa where invasive pneumococcal disease is
      prevalent. METHODS: Thirty Gambian infants were vaccinated with 3 doses of a five
      valent pneumococcal conjugate vaccine containing 5 micrograms of type 6B, 14, 18,
      19F and 23F polysaccharides conjugated to the diphtheria toxin mutant protein
      CRM197 at the ages of 2, 3 and 4 months; 30 infants received 2 doses at the ages
      of 2 and 4 months and 30 infants who received three doses of a Haemophilus
      influenzae type b vaccine acted as controls. Local and systemic reactions were
      recorded after vaccination and antibody titers were measured by an enzyme-linked
      immunosorbent assay. RESULTS: No serious local or systemic reactions to
      vaccination were recorded. Antibody responses to each component of the vaccine
      were demonstrated. One month after immunization with three doses of vaccine,
      antibody titers were 3 to 11 times higher than before vaccination
      (postvaccination titers ranged from 2.49 micrograms/ml for type 19 polysaccharide
      to 7.59 micrograms/ml for type 14). Elevated titers were well-maintained during
      the subsequent 4 months. Three doses of vaccine induced higher titers than did
      two doses. Antibody titers increased 2- to 3-fold over the period of immunization
      in children who received H. influenzae type b vaccine. CONCLUSIONS: A five-valent
      pneumococcal conjugate vaccine proved safe and immunogenic in Gambian infants.
      However, a vaccine containing a larger number of serotypes will be necessary to
      achieve a maximal clinical impact.

PMID- 8866804
TI  - In vitro lymphocyte blastogenic responses and cytokine production in sickle cell
      disease patients with acute pneumonia.
AB  - BACKGROUND: Pulmonary infections continue to be a major cause of morbidity and
      mortality in patients with sickle cell disease (SCD). METHODS: In this study cell
      mediated immunity in vitro was evaluated in 62 SCD patients (62 steady state and
      16 with acute pneumonia) and compared with 44 normal controls (30 healthy and 14
      with acute pneumonia). Lymphocyte blastogenic responses to phytohemagglutinin,
      tetanus toxoid and Candida albicans antigen were assessed in all subjects. In
      addition production of tumor necrosis factor, alpha- and gamma-interferon (IFN)
      were assayed. RESULTS: The results revealed comparable blastogenic responses to
      all three stimuli in all subjects except SCD patients with pneumonia. This group
      showed poor responses to all stimuli. The mean counts per minute were decreased
      65 to 90% when compared with the other patients. Cytokine production of IFN-alpha
      and TNF was equivalent in all subjects. Conversely IFN-gamma production in both
      SCD groups, steady state (35 +/- 6 U/ml) and SCD with pneumonia (14 +/- 6 U/ml),
      was significantly decreased when compared with those in normal healthy controls
      (65 +/- 14 U/ml) and with pneumonia (48 +/- 17 U/ml). On analysis of individual
      titers 15 of 62 (24%) steady state and 10 of 16 (63%) SCD patients with pneumonia
      were deficient in IFN-gamma production in vitro. CONCLUSIONS: Acute pulmonary
      infections seem to have a profound effect on cell-mediated immunity in SCD. IFN
      gamma deficiency, along with quantitative and qualitative T cell abnormalities,
      may represent significant factors to explain the frequent and severe infections
      seen in SCD.

PMID- 8866805
TI  - Campylobacter bacteremia in children.
AB  - OBJECTIVE: To describe clinical and laboratory data for, and to propose
      pathogenesis and management of, children from impoverished communities with
      Campylobacter bacteremia. METHODS: A retrospective review of patient data
      generated from laboratory records in an urban tertiary care hospital in Soweto
      and a rural mission hospital in Eastern Transvaal, South Africa. Participants
      were 19 children presenting to either hospital with Campylobacter bacteremia.
      Clinical and laboratory data were collated. RESULTS: Nineteen children with
      Campylobacter bacteremia were identified; all isolates were Campylobacter jejuni.
      Sixteen (84%) had malnutrition; 13 of these were severely malnourished. Thirteen
      (68%) were febrile at the time of bacteremia. Four children (21%) did not have
      diarrhea. The case fatality rate was 16% and may not have been influenced by
      aminoglycoside administration. CONCLUSION: Malnourished children may be more
      likely to have gastrointestinal C. jejuni infection. Immunodeficiency and
      intestinal mucosal compromise secondary to malnutrition may render such children
      at increased risk of C. jejuni bacteremia and its consequences. C. jejuni
      bacteremia is potentially life-threatening and should be managed accordingly.

PMID- 8866806
TI  - Invasive candidiasis in infants weighing more than 2500 grams at birth admitted
      to a neonatal intensive care unit.
AB  - BACKGROUND: Because invasive candidiasis in newborn infants admitted to a
      neonatal intensive care unit (NICU) occurs most frequently in very low birth
      weight infants, the incidence of invasive candidiasis and its clinical features
      in infants > 2500 g birth weight have not been well-described. METHODS: We
      retrospectively reviewed the medical records of all infants with birth weight >
      2500 g admitted to our NICU from 1986 through 1993 who developed invasive
      candidiasis during their hospitalization. RESULTS: Seventeen of 3033 (0.6%)
      infants with birth weights > 2500 g admitted to the NICU developed invasive
      candidiasis. All 17 infants had a condition that required prolonged NICU
      hospitalization; 13 of 17 (76%) had a major congenital malformation. CONCLUSION:
      The incidence of invasive candidiasis in infants with birth weights > 2500 g
      requiring admission to a NICU was much less than has been reported for very low
      birth weight infants. This review points out that in infants with birth weights >
      2500 g who develop invasive candidiasis, major congenital malformations are the
      most frequent underlying conditions responsible for prolonged NICU
      hospitalization.

PMID- 8866807
TI  - Treatment of cutaneous sporotrichosis with one daily dose of potassium iodide.
AB  - BACKGROUND: Recommended treatment for cutaneous sporotrichosis consists of a
      saturated solution of potassium iodide (SSKI) administered in three daily doses
      (tid). Because compliance with this regimen has been a problem in our previous
      experience, we evaluated the use of one daily (qd) full dose of SSKI. METHODS:
      Patients with culture-confirmed cutaneous sporotrichosis were entered in a
      randomized, nonblinded study to compare the safety and efficacy of qd vs. tid
      dosage of SSKI. RESULTS: Fifty-seven patients were enrolled to receive either qd
      (29) or tid (28) SSKI. Three (1 in the qd and 2 in the tid group) were not
      compliant with the assigned regimen. Side effects were common but mild in both
      treatment groups (61% in the qd and 42% in the tid group, P = 0.17); treatment
      had to be discontinued because of side effects in 3 cases (2 in the qd and 1 in
      the tid group). Overall 26 (89.6%) and 25 (89.2%) of the individuals initially
      assigned to the qd and tid dosing schedule, respectively, were cured by the
      treatment. No relapse was detected after 45 days of follow-up. CONCLUSION: These
      findings suggest that a single daily full dose of SSKI appears to be appropriate
      therapy for cutaneous sporotrichosis; further studies with larger numbers of
      patients are required.

PMID- 8866808
TI  - Immune responses to infectious diseases: an evolutionary perspective.

PMID- 8866809
TI  - Fatal Pseudallescheria boydii panencephalitis in a child after near-drowning.

PMID- 8866810
TI  - Prospective comparative study of viral, bacterial and atypical organisms
      identified in pneumonia and bronchiolitis in hospitalized Canadian infants.

PMID- 8866811
TI  - Peripheral thrombophlebitis caused by Candida.

PMID- 8866812
TI  - Staphylococcus aureus endocarditis associated with varicella infection in
      children.

PMID- 8866813
TI  - Recurrence of pneumococcal sepsis caused by an intermediately penicillin
      resistant organism treated with loracarbef.

PMID- 8866814
TI  - Left ventricular pseudoaneurysm: an unusual complication of pericarditis and
      Staphylococcus aureus septicemia.

PMID- 8866815
TI  - Primary hepatic actinomycosis.

PMID- 8866816
TI  - Successful treatment of chronic Mycobacterium abscessus otitis media with
      clarithromycin.

PMID- 8866817
TI  - Severe esophagitis in a newborn infant.

PMID- 8866818
TI  - Pathogenic mechanisms of Bartonella henselae infections.

PMID- 8866819
TI  - Early diagnosis and management of herpes simplex encephalitis.

PMID- 8866820
TI  - Agonist-releasable intracellular calcium stores and the phenomenon of store
      dependent calcium entry. A novel hypothesis based on calcium stores in organelles
      of the endo- and exocytotic apparatus.
AB  - Store-dependent calcium entry represents a little characterized calcium
      permeation pathway that is present in a variety of cell types. It is activated in
      an unknown way by depletion of intracellular calcium stores, for example in the
      course of phospholipase C stimulation. Current hypotheses propose that depleted
      calcium stores signal their filling state to this permeation pathway either by
      direct, protein-mediated interaction or by release of a small, diffusible
      messenger. The further characterization of store-dependent calcium entry will
      benefit from progress in the identification of the intracellular calcium storing
      compartments. Recent findings reviewed here suggest that these compartments
      include parts of the organelle system that is involved in endo- and exocytosis.
      This commentary describes a novel model of store-dependent calcium entry based on
      calcium stores belonging to the endo- and exocytotic organelle system. Such
      calcium stores could establish a tubule-like connection with the extracellular
      space, in analogy to the cellular compartments that contain the insulin-sensitive
      glucose transporter or the gastric proton pump. This connection will provide a
      pathway for store-dependent calcium entry. Under store depletion, extracellular
      calcium will permeate through the tubule-like connection into the store lumen and
      from there into the cytosol. The consequences of this model for the development
      of drugs modulating store-dependent calcium entry are discussed.

PMID- 8866821
TI  - Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O
      demethylation of R- and S-naproxen.
AB  - A preliminary report implicated cytochrome P450 (CYP) 2C9 in the human liver
      microsomal O-demethylation of S-naproxen, suggesting that this pathway may be
      suitable for investigation of human hepatic CYP2C9 in vitro. Kinetic and
      inhibitor studies with human liver microsomes and confirmatory investigations
      with cDNA-expressed enzymes were undertaken here to define the role of CYP2C9 and
      other isoforms in the O-demethylation of R- and S-naproxen. All studies utilised
      a newly developed sensitive and specific HPLC assay that measured the respective
      O-desmethyl metabolites of R- and S-naproxen in incubations of human liver
      microsomes and in COS cell lysates. Microsomal R- and S-naproxen O-demethylation
      kinetics followed Michaelis-Menten kinetics, with respective mean apparent Km
      values of 123 microM and 143 microM. Sulfaphenazole, a specific inhibitor of
      CYP2C9, reduced the microsomal O-demethylation of R- and S-naproxen by 43% and
      47%, respectively, and the CYP1A2 inhibitor furafylline decreased R- and S
      naproxen O-demethylation by 38% and 28%, respectively. R,S-Mephenytoin was a weak
      inhibitor of R- and S-naproxen O-demethylation, but other CYP isoform specific
      inhibitors (e.g., coumarin, diethyldithiocarbamate, quinidine, troleandomycin)
      had little or no effect on these reactions. cDNA-expressed CYP2C9 and CYP1A2 were
      both shown to O-demethylate R- and S-naproxen. Apparent Km values (92-156 microM)
      for the reactions catalysed by the recombinant enzymes were similar to those
      observed for human liver microsomal R- and S-naproxen O-demethylation. The data
      demonstrate that CYP2C9 and CYP1A2 together account for the majority of human
      liver R- and S-naproxen O-demethylation, precluding the use of either R- or S
      naproxen as a CYP isoform-specific substrate in vitro and in vivo.

PMID- 8866822
TI  - Photoaffinity labeling of peripheral benzodiazepine receptors in R-3327 Dunning
      prostatic tumors.
AB  - Photoaffinity labeling of peripheral benzodiazepine receptors (PBZr) in
      mitochondrial and microsomal fractions from AT-1, H, and G Dunning R-3327 tumor
      sublines was performed using the photoaffinity ligand 3H-PK 14105. Subsequent
      sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis (PAGE) revealed
      specific labeling of a 17 kDa protein in the microsomal fractions from these
      tumors. In the mitochondrial fractions, however, two bands with the apparent
      molecular mass of 17 and 18 kDa in AT-1 and H tumors were identified, whereas
      only the 17 kDa band was present in G tumors. Using another ligand, 3H
      flunitrazepam, to photoaffinity label PBZr, proteins with molecular masses of 17,
      30, 42, and 48 kDa were identified. These data suggest the possibility of
      different subclasses of PBZrs in Dunning prostatic tumors.

PMID- 8866823
TI  - Inhibition of selenite-catalyzed superoxide generation and formation of elemental
      selenium (Se(o)) by copper, zinc, and aurintricarboxylic acid (ATA).
AB  - Selenite catalyzes the oxidation of glutathione (GSH) with the subsequent
      generation of superoxide (O2.-). Copper, zinc, and aurintricarboxylic acid (ATA)
      were tested for their ability to inhibit both the selenite-catalyzed generation
      of superoxide and the conversion of selenite to elemental selenium (Se(o)). As
      measured by lucigenin-dependent chemiluminescence (CL), copper, zinc, and ATA
      were shown to inhibit significantly (P < 0.05) selenite-catalyzed CL in a
      concentration-dependent manner. The inhibition of the selenium-catalyzed
      generation of superoxide by copper(II) was greater than by either zinc or ATA. In
      addition, Copper, zinc, and ATA all inhibited the conversion of selenite to
      Se(o). Inhibition of selenite-catalyzed CL by copper, zinc, and ATA is believed
      to occur as the result of inhibition of Se2- and/or GSSe-, the catalytic
      selenopersulfide anion of GSH.

PMID- 8866824
TI  - Isolation and preliminary characterization of a Chinese hamster ovary cell line
      with high-degree resistance to hydrogen peroxide.
AB  - We have isolated and conducted preliminary characterization of a cell line
      derived from the Chinese hamster ovary cell line AA8, which we have designated
      AG8 and which is highly resistant to the cytotoxic effects of H2O2 (approximately
      17-fold when the H2O2 treatment was at 37 degrees; approximately 11-fold when the
      H2O2 treatment was at 4 degrees). AG8 cells were moderately (but significantly; P
      < 0.05) cross-resistant to CdCl2 (approximately 4-fold), NaAsO2 (approximately
      2.3-fold), t-butyl hydroperoxide (approximately 2.9-fold), cumene hydroperoxide
      (approximately 3-fold), menadione (approximately 1.7-fold) and HgCl2
      (approximately 1.5-fold), but were not significantly cross-resistant to
      hyperthermia (43 degrees), 254 nm UV light, 137Cs gamma-rays, and 42-MeV (p-
      >Be+) fast neutrons. As regards their biochemical status, AG8 and AA8 cells
      contain similar non-protein sulfhydryl levels per milligram of protein. Catalase
      activity (assessed by both spectrophotometry and polarography) was significantly
      higher in AG8 than in AA8 cells irrespective of whether enzyme activity was
      expressed per 10(6) cells (approximately 3.6-fold increase) or per milligram of
      protein (approximately 1.6-fold increase). AG8 cells also exhibited significantly
      greater glutathione reductase activity than wild-type cells when the data were
      expressed per 10(6) cells (approximately 2.9-fold) or per milligram of protein
      (approximately 1.3-fold). Glutathione peroxidase activity was immeasurably low in
      both cell lines. The susceptibility of the two cell lines to H2O2-mediated
      generation of DNA single-strand breaks (as measured by alkaline elution)
      indicated a slightly (approximately 1.5-fold) decreased yield in the resistant
      AG8 cell line. The two cell lines repaired these breaks with similar kinetics. In
      contrast, no measurable induction of DNA double-strand breaks (as measured by
      pulsed-field gel electrophoresis) was apparent in either cell line after survival
      curve range concentrations of H2O2. On the basis of these data, it appears that
      the AG8 phenotype involves two previously identified resistance mechanisms,
      namely an adaptive component that may or may not involve increased antioxidant
      capacity, and a second component that does involve increased antioxidant
      (primarily catalase) capacity.

PMID- 8866825
TI  - Involvement of nitric oxide in nitroprusside-induced hepatocyte cytotoxicity.
AB  - Sodium nitroprusside (SNP) cytotoxicity towards rat hepatocytes was accompanied
      by peroxynitrite formation, lipid peroxidation, inhibition of glycolysis, cyanide
      (CN) release, partial inhibition of hepatocyte respiration, and ATP depletion.
      Antioxidants and desferoxamine prevented both cytotoxicity and lipid peroxidation
      induced by SNP. The CN antidote thiosulfate or the CN trapping agents
      dihydroxyacetone and glyceraldehyde increased SNP metabolism, SNP-induced
      peroxynitrite formation, cytotoxicity, and lipid peroxidation. On the other hand,
      addition of non-toxic concentrations of CN to hepatocytes prevented SNP
      metabolism and SNP-induced lipid peroxidation and cytotoxicity. SNP depleted
      hepatocyte GSH immediately upon addition, and GSH-depleted hepatocytes were more
      susceptible to SNP. The results of this study suggest that nitric oxide rather
      than CN mediates SNP cytotoxicity in isolated cells.

PMID- 8866826
TI  - Multiple forms of human P450 expressed in Saccharomyces cerevisiae. Systematic
      characterization and comparison with those of the rat.
AB  - We systematically characterized the levels and substrate specificity of P450s
      from humans and rats to extrapolate drug metabolism data from experimental
      animals to humans. Human P450s (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2D6, 2E1, and
      3A4) were expressed in Saccharomyces cerevisiae and purified. Rat P450s were
      purified from hepatic microsomes of rats. We investigated the catalytic
      activities of purified P450s in a reconstituted system. Human CYP2B6 and rat
      CYP2B1 had high lidocaine N-deethylation activity. Human and rat CYP2D forms had
      high debrisoquine 4-hydroxylation activity. Human CYP3A4 and rat CYP3A2 had high
      testosterone 2 beta- and 6 beta-hydroxylation activities in a modified
      reconstituted system with a lipid mixture. The hydroxylation site of testosterone
      by CYP2B6 (16 alpha- and 16 beta-positions) agreed with that by rat CYP2B1. Human
      CYP2E1 had the highest lauric acid (omega-1)-hydroxylation activity and also had
      catalytic properties similar to those of rat CYP2E1. Human CYP2A and 2C forms had
      catalytic properties in testosterone metabolism different from those of rats.
      Antibodies raised against purified P450s were used to measure the levels of
      hepatic P450s. The level of CYP3A4 was the highest in human hepatic microsomes,
      comprising 30-40% of the total P450. CYP2C9 comprised 10-20% of the total. The
      levels of CYP1A2, 2A6, 2C8, 2D6, and 2E1 were moderate (5-15% of total P450).
      CYP2B6 content was very low. The information of this study is useful for drug
      metabolism and toxicological studies.

PMID- 8866827
TI  - Inhibition of angiotensin converting enzyme and potentiation of bradykinin by
      retro-inverso analogues of short peptides and sequences related to angiotensin I
      and bradykinin.
AB  - There is pharmacological evidence indicating that, in addition to the inhibition
      of angiotensin converting enzyme (ACE; EC 3.4.15.1), the potentiation of
      bradykinin (BK) responses may also involve the BK receptor or some binding site
      in the structures involved in the contractile response to this peptide.
      Dipeptides such as Val-Trp and some of its analogues as well as tripeptide
      homologues, including total and partial retro-inverso peptides, were synthesized
      and assayed for their ability to inhibit purified guinea pig plasma ACE and to
      potentiate the action of BK on the isolated ileum of the same species. The
      peptides containing the P2-P1, P1-P'1, and P'1-P'2 inverted amide bonds inhibited
      ACE, were resistant to hydrolysis, and, depending on the amino acid composition,
      some of them potentiated the contractile response to BK while others did not. Des
      [Arg1]-BK, which has an intrinsic activity at concentrations higher than 10(-5)
      M, and the very dissimilar angiotensin I (AI) analogue [Cys5-Cys10]-angiotensin-I
      (5-10)-amide, which has no detectable contractile activity, were able to inhibit
      ACE and potentiate BK. In contrast to these peptides, BPP5a and BPP9a from
      Bothrops jararaca venom, and Potentiators B and C from Agkistrodon halys
      blomhoffi venom were more effective as BK potentiators than as ACE inhibitors. In
      conclusion, we have synthesized and assayed compounds that preferentially inhibit
      ACE, e.g. retro-inverso tripeptides, or potentiate the response of smooth muscle
      to BK, e.g. snake venom peptides.

PMID- 8866828
TI  - Pervanadate stimulation of wortmannin-sensitive and -resistant 2-deoxyglucose
      transport in adipocytes.
AB  - Pervanadate mimics several distinct insulin effects, including stimulation of
      hexose uptake in the in vitro system, and reduces the blood glucose level in
      streptozotocin-treated diabetic rats. It has been proposed that pervanadate
      induces insulin-like effects mediated through autophosphorylation and activation
      of insulin receptor (IR) even in the absence of insulin by inhibiting protein
      tyrosine phosphatases. This study focused on the mechanism of pervanadate action
      on hexose uptake. Both insulin (100 nM) and pervanadate (100 microM), a protein
      tyrosine phosphatase inhibitor, induced a marked increase in the phosphorylation
      at tyrosine residues of IR and insulin receptor substrate 1 (IRS-1) and in 2
      deoxyglucose uptake in 3T3-L1 adipocytes. Wortmannin (1 microM), a specific
      phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, inhibited the increased 2
      deoxyglucose uptake by insulin completely but that by pervanadate only partially.
      On the other hand, both insulin- and pervanadate-stimulated PI 3-kinase
      activities were inhibited completely by wortmannin (100 nM), suggesting that the
      pervanadate-induced wortmannin-resistant effect on hexose uptake may be mediated
      through a PI 3-kinase-independent pathway. This pervanadate-induced wortmannin
      resistant effect was abolished by ST-638, a specific tyrosine kinase inhibitor.
      These data suggest that at least two distinct tyrosine phosphorylation pathways
      may be involved in the insulin-like effect of pervanadate.

PMID- 8866829
TI  - Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists
      and antagonists in T47D human breast cancer cells.
AB  - Indole-3-carbinol (I3C) is a major component of Brassica vegetables, and
      diindolylmethane (DIM) is the major acid-catalyzed condensation product derived
      from I3C. Both compounds competitively bind to the aryl hydrocarbon (Ah) receptor
      with relatively low affinity. In Ah-responsive T47D human breast cancer cells,
      I3C and DIM did not induce significantly CYP1A1-dependent ethoxyresorufin O
      deethylase (EROD) activity or CYP1A1 mRNA levels at concentrations as high as 125
      or 31 microM, respectively. A 1 nM concentration of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) induced EROD activity in these cells, and cotreatment with TCDD
      plus different concentrations of I3C (1-125 microM) or DIM (1-31 microM) resulted
      in a > 90% decrease in the induced response at the highest concentration of I3C
      or DIM. I3C or DIM also partially inhibited (< 50%) induction of CYP1A1 mRNA
      levels by TCDD and reporter gene activity, using an Ah-responsive plasmid
      construct in transient transfection assays. In T47D cells cotreated with 5 nM
      [3H]TCDD alone or in combination with 250 microM I3C or 31 microM DIM, there was
      a 37 and 73% decrease, respectively, in formation of the nuclear Ah receptor. The
      more effective inhibition of induced EROD activity by I3C and DIM was due to in
      vitro inhibition of enzyme activity. Thus, both I3C and DIM are partial Ah
      receptor antagonists in the T47D human breast cancer cell line.

PMID- 8866830
TI  - Substituted flavones as aryl hydrocarbon (Ah) receptor agonists and antagonists.
AB  - The structure-dependent aryl hydrocarbon (Ah) receptor agonist and antagonist
      activities of the following substituted flavones were investigated: flavone, 4'
      methoxy-, 4'-amino-, 4'-chloro-, 4'-bromo-, 4'-nitro-, 4'-chloro-3'-nitro-, 3'
      amino-4'-hydroxy-, 3',4'-dichloro-, and 4'-iodoflavone. The halogenated flavones
      exhibited competitive Ah receptor binding affinities (IC50 = 0.79 to 2.28 nM)
      that were comparable to that observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) (1.78 nM). The compounds also induced transformation of the rat cytosolic
      Ah receptor and induced CYP1A1 gene expression in MCF-7 human breast cancer
      cells. However, despite the high Ah receptor binding affinities for these
      responses, the halogenated flavones were > 1000 times less active than TCDD for
      the other responses. Moreover, for other substituted flavones, there was no
      correlation between Ah receptor binding affinities and their activities as Ah
      receptor agonists. For example, 4'-aminoflavone induced CYP1A1 mRNA levels in MCF
      7 cells but exhibited relatively low Ah receptor binding affinity (IC50 = 362 nM)
      and did not induce transformation of the rat cytosolic Ah receptor. All of the
      substituted flavones inhibited TCDD-induced transformation of the Ah receptor,
      and 4'-iodoflavone, an Ah receptor agonist at high concentrations (1-50 microM),
      inhibited the transformation at concentrations as low as 0.05 and 0.5 microM.
      Subsequent interaction studies with TCDD and 4'-iodoflavone confirmed that the
      latter compound inhibits induction of CYP1A1 gene expression by TCDD in MCF-7
      cells. The results obtained for the substituted flavones suggest that within this
      structural class of compounds, various substituent groups can affect markedly the
      activity of each individual congener as an Ah receptor agonist or antagonist.
      These substituent-dependent differences in activity may be related to ligand
      induced conformational changes in the Ah receptor complex and/or support the
      proposed existence of more than one form of the Ah receptor.

PMID- 8866831
TI  - Tissue-specific developmental regulation of protein kinase C isoforms.
AB  - The limited amount of available information regarding the developmental control
      of protein kinase C (PKC) isoform expression restricts our understanding of the
      role of these enzymes in normal physiology. Accordingly, this study investigated
      PKC isoform expression in selected tissues from fetal, neonatal, and adult rats.
      PKC beta immunoreactivity was prominent in brain tissue, whereas the expression
      of PKC alpha, PKC delta, PKC epsilon, and PKC zeta was found to be widespread.
      Although no developmental change in any PKC isoform was evident in liver,
      striking tissue-specific age-dependent differences in PKC isoform abundance were
      noted in other tissues. For example, age-dependent increases in PKC alpha, PKC
      beta, and PKC delta in brain contrasted with age-dependent decreases in PKC alpha
      and PKC delta in lung, kidney, and heart. Immunoreactivity for PKC epsilon was
      abundant in all fetal/neonatal tissues; PKC epsilon was detected in the adult
      brain, heart, and liver, but not the adult kidney and lung. Finally, PKC zeta was
      more abundant in fetal/neonatal than in adult brain, lung, kidney, and heart.
      These results indicate that the fetal/neonatal lung, kidney, and heart are
      enriched in PKC zeta, PKC alpha, PKC delta, and PKC epsilon, relative to the
      adult tissues. These age-dependent variations in the abundance of individual
      isoforms of PKC may critically influence tissue responsiveness to external
      stimuli. Moreover, the finding that PKC zeta is particularly abundant in fetal
      tissues as well as the liver, the only tissue included in this study which
      retains regenerative capacity in the adult animal, is consistent with the notion
      that PKC zeta may play a role in cell proliferation.

PMID- 8866832
TI  - Paraquat toxicity and oxidative damage. Reduction by melatonin.
AB  - The ability of melatonin to protect against paraquat-induced oxidative damage in
      rat lung, liver, and serum was examined. Changes in the levels of malondialdehyde
      (MDA) plus 4-hydroxyalkenals (4-HDA) and reduced and oxidized glutathione
      concentrations were measured. Paraquat (50 mg/kg) was injected i.p. into either
      Sprague-Dawley or Wistar rats with or without the co-administration of 5 mg/kg
      melatonin. Paraquat alone increased MDA + 4-HDA levels in serum and lungs of both
      rat strains, with these increases being abolished by melatonin co-treatment.
      Paraquat also decreased reduced glutathione levels and increased oxidized
      glutathione concentrations in lung and liver; these changes were negated by
      melatonin. The effect of melatonin on paraquat-induced mortality was also
      studied. Paraquat at a dose of 79 mg/kg was lethal for 50% of animals within 24
      hr; when administered together with melatonin, the LD50 for paraquat increased to
      251 mg/kg.

PMID- 8866833
TI  - Inducing properties of rifabutin, and effects on the pharmacokinetics and
      metabolism of concomitant drugs.
AB  - Rifabutin, a rifamycin derivative like rifampicin, has been registered for the
      treatment of pulmonary tuberculosis and for the prophylaxis and treatment of MAC
      in patients with AIDS. Rifabutin induces cytochrome P-450 3A4. The effect of
      rifabutin on the pharmacokinetics and metabolism of drugs administered
      concomitantly to humans (isoniazid, ethambutol, zidovudine, didanosine,
      delavirdine, fluconazole, itraconazole, methadone, clarithromycin, theophylline
      and cyclosporin) has been reviewed.

PMID- 8866834
TI  - FCE 27677: a novel inhibitor of acyl-CoA: cholesterol acyltransferase with potent
      oral hypolipidemic activity.
AB  - FCE 27677 ([(-)N-[2,6-bis(1-methylethyl)phenyl]-N'-[(4R,5R)-2- (4
      dimethylaminophenyl)-4,5 dimethyl-dioxolan-2-yl]methylurea) is a new systemically
      available ACAT inhibitor belonging to the class of ketalic disubstituted ureas.
      When tested in microsomes from rabbit intestine, aorta and liver, it inhibited
      the enzyme with IC50 of 9.31, 6.99 and 92.2 nM, respectively. It had no effect on
      plasma LCAT and intestinal cytosolic cholesterol esterases and, when tested in a
      tissue culture system, it did not interfere with the synthesis of cholesterol,
      triglycerides, and phospholipids. Enzyme inhibition kinetics indicated that FCE
      27677 is a non-competitive inhibitor of the enzyme with respect to acylCoA and to
      cholesterol. When administered mixed to a 1.5% cholesterol and 0.5% sodium
      cholate-enriched diet to rats, it prevented the development of
      hypercholesterolemia with ED50 of 0.35 mg kg-1 day-1. Given in a single oral dose
      to hypercholesterolemic rats it significantly reduced both the plasma lipid
      levels and the hepatic cholesteryl ester content within 6 h from gavage. VLDL and
      LDL levels and composition were also significantly affected. Similar effects were
      observed when the drug was given mixed to a regular chow diet for 4 weeks to
      hypercholesterolemic rabbits. These results are consistent with the idea that
      systemically available ACAT inhibitors can affect the composition and the
      metabolism of the atherogenic cholesteryl ester-rich VLDL and LDL. ACAT
      inhibitors appear promising for the correction of dyslipoproteinemias secondary
      to lipoprotein overproduction, and in reducing the atherogenic index of apoB-100
      containing lipoproteins.

PMID- 8866835
TI  - Effects of rebamipide on gastric cell damage by Helicobacter pylori-stimulated
      human neutrophils.
AB  - Helicobacter pylori stimulated human neutrophils to produce oxygen radicals as
      evidenced by the production of chemiluminescence in the presence of luminol. The
      capacity of H. pylori to produce oxygen radicals from neutrophils was much higher
      than that of Escherichia coli and Staphylococcus aureus and is almost as strong
      as that of PMA. Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl]
      propionic acid) suppressed the chemiluminescence produced by H. pylori-stimulated
      neutrophils and also suppressed the chemiluminescence produced by a cell-free
      xanthine/xanthine oxidase reaction with luminol. Thus, it is indicated that this
      drug has the action of scavenging oxygen radicals. Gastric mucosal cells labelled
      with a fluorescent dye were damaged by the incubation of the cells with
      neutrophils and H. pylori, and this damage was protected by rebamipide. The
      protection of cell damage was ascertained as a decrease in the release of
      fluorescent dye into the incubation medium and a reduction in the distortion of
      cell geometry. The data suggest that H. pylori induce human neutrophils to
      produce oxygen radicals which are responsible for gastric mucosal cell damage and
      that rebamipide removes the oxygen radicals produced from H. pylori-activated
      neutrophils and thus reduces the gastric mucosal cell damage. These effects may
      account for the ulcerogenesis action of H. pylori and for part of the mechanism
      of the anti-ulcer action of rebamipide.

PMID- 8866836
TI  - Studies on the effect of intragastric capsaicin on gastric ulcer and on the
      prostacyclin-induced cytoprotection in rats.
AB  - The effect of intragastric (i.g.) capsaicin on experimental gastric ulcer was
      studied in the 1 h pylorus-ligated rats. Capsaicin applied in 40 ng ml-1
      concentration (0.1 microgram kg-1) protected against gastric mucosal injury
      evoked by i.g. application of acidified aspirin, 96% ethanol or 0.6 M HCl. After
      a capsaicin concentration of 400 micrograms ml-1 (1 mg kg-1) protection occurred
      initially, while several hours later mucosal damage evoked by acidified aspirin
      was enhanced. Capsaicin in 2 and 6 ml kg-1 (10 and 30 mg kg-1) invariably
      aggravated the aspirin and ethanol-induced gastric mucosal damage. Capsaicin in
      0.1 microgram kg-1 did not modify the mucosal protective action of prostacyclin
      (5 micrograms kg-1) on gastric mucosal injury produced by i.g. application of
      acidified aspirin, 96% ethanol or 0.6 M HCl. Local capsaicin desensitization
      induced by application of capsaicin in 2 mg ml-1 (10 mg kg-1) did not interfere
      with the mucosal cytoprotective effects of prostacyclin against ethanol and
      aspirin-induced mucosal damage. It is concluded that i.g. capsaicin exerts a dual
      dose-dependent effect on development of experimental gastric ulcer. Neither i.g.
      capsaicin in small doses nor local capsaicin desensitization modify the mucosal
      cytoprotective effects of prostacyclin.

PMID- 8866837
TI  - In vitro binding of 16-methylated C18 and C19 steroid derivatives to the androgen
      receptor.
AB  - The binding of androgens and structurally related analogues to the androgen
      receptor was studied. The in vitro experiments were carried out with cytosol of
      castrated rat prostate, using [3H]R1881 (methyltrienolone) as radioligand. The
      binding parameters measured were Kd = 1.25 x 10(-10) M and Bmax = 111 fmol (mg
      protein)-1. Ligand specificity was confirmed by competition experiments with
      known androgen, oestrogen and progestogen ligands. The receptor binding of
      substituted steroids was studied. The RBAs (relative binding affinities) of our
      recently synthetized 16-alkyl steroids were low. The only exception was the 17
      beta-hydroxy-16 beta-methylestr-4-en-3-one, which exhibited the remarkable RBA of
      22.9%.

PMID- 8866838
TI  - Discrimination of transport systems for methylmercury uptake in rat erythrocytes
      using methylmercury-mercaptalbumin by inhibitors and other factors.
AB  - This is a continuation of studying the transport system for the uptake of
      methylmercury (MeHg). The aim of the current study was to study transport systems
      in rat erythrocyte for the uptake of MeHg while using MeHg-mercaptalbumin
      (MeHgMASH) complex. The uptake of methylmercury was studied in isolated
      erythrocytes from rats at 5 degrees C. Different reagents were used to study
      different transport systems in rat erythrocytes: adenosine 5'-triphosphate (ATP),
      ouabain and sodium fluoride for the active transport systems; probenecid for the
      organic anion transport system; 4',4-diisothiocyano-2',2-stilbenedisulphonic acid
      (DIDS), maleimide and N-ethylmaleimide for Cl- transport system; verapamil for
      Ca2+ ion transport system; colchicine and vinblastine for the microtubule system;
      verapamil for Ca2+ ion transport system; colchicine and vinblastine for the
      microtubule system; valinomycin for the effect of membrane potential; hexanol for
      the protein-mediated transport system and nonelectrolyte diffusion. The results
      showed that the uptake of MeHg might be involved in several transport systems:
      the active transport systems, an organic anion transport system, Cl- ion
      transport system, and Ca2+ ion transport system. The transport systems were
      slightly sensitive to the membrane potential. These transport systems seem to
      share similarities with the transport systems for the uptake of MeHg when using
      MeHg-cysteine and MeHg-glutathione complexes.

PMID- 8866839
TI  - Acute zinc administration prolongs hexobarbitone-induced sleeping time in C57/6J
      mice.
AB  - Two experiments were carried out in this study to demonstrate the effects of
      acute intraperitoneal (i.p.) administration of zinc chloride (ZnCl2) on
      hexobarbitone-induced sleeping time (HST) in female C57/6J mice. Serum and
      hepatic zinc content as well as hepatic cytochrome P450 content were also
      estimated in ZnCl2-treated and control mice. The ZnCl2 dose used was equal to the
      LD50 for chronic treatment (which was 28 micrograms g-1 body weight for mice
      given i.p. ZnCl2 five times a week for 3 weeks), determined in an earlier
      experiment. ZnCl2 injections at this dose were either given singly (in experiment
      I) or repeated on two mornings (in experiment II). Hexobarbitone, an ultra-short
      acting experimental barbiturate, was given intraperitoneally 30 min after the
      single ZnCl2 injection in experiment I and 24 h after the second ZnCl2 injection
      in experiment II. Appropriate controls were given i.p. normal saline in each
      experiment. The HST was observed for all the animals, using the time-points at
      which the loss and regain of righting reflex occurred as the parameters. The
      animals were later killed; their blood and livers were obtained for estimation of
      zinc levels and cytochrome P450 content. The results of both experiments showed
      that ZnCl2 had caused a significant prolongation of the HST in C57/6J mice. Serum
      and hepatic zinc content were also elevated in both groups of ZnCl2-treated mice
      compared to their respective controls. The cytochrome P450 content in the single
      dose ZnCl2-treated mice was unchanged while it was significantly reduced in the
      double-dose ZnCl2-treated mice when compared to the content in their respective
      controls. These findings suggest that acute zinc excess has an inhibitory effect
      on the function as well as the synthesis of hepatic cytochrome P450 enzymes.

PMID- 8866840
TI  - Open questions in bioequivalence.
AB  - Bioequivalence studies are mainly required to demonstrate the interchangeability
      of multisource pharmaceutical products, usually called generics. A pivotal
      investigation projected and conducted in compliance with specific guidelines
      allows a replicative company to register a generic drug via an ANDA (abbreviated
      new drug application) procedure. Serious problems are often encountered in
      planning and conducting these studies, which are not covered by operating
      guidelines, and call for protocols to be set up on a case-by-case basis. The main
      problems involve the high variability of some active ingredients, how to manage
      baseline with endogenous substances, drugs with a long terminal half-life, drugs
      under genetic polymorphic metabolism, drugs possessing stereogenic centre(s), and
      drugs which cannot ethically be given to healthy volunteers. These problems are
      extensively covered in this paper and, where appropriate, possible solutions are
      suggested.

PMID- 8866841
TI  - Calculating percentage prediction error: a user's note.
AB  - The equations of calculation of percentage prediction error (percentage
      prediction error = [equation: see text] x 100 or percentage prediction error =
      [equation: see text] x 100) and similar equations have been widely used. However,
      not much is known about the property of this type of equation and the caution
      which should be taken into account when using this type of equation. Moreover,
      little is known about the power of percentage prediction error as statistical
      inference. In the present study we address these points in the use of this type
      of equation.

PMID- 8866842
TI  - Expression of extracellular matrix molecules and cell surface molecules in the
      olfactory nerve pathway during early development.
AB  - The spatial and temporal expression patterns of several extracellular matrix
      molecules--laminin and fibronectin and cell surface molecules, neural cell
      adhesion molecule (NCAM), L1, tenascin, chondroitin sulfate proteoglycan, and
      peanut agglutinin (PNA) binding sites--were investigated during early olfactory
      nerve development. NCAM and L1 have similar patterns: They are expressed in the
      olfactory nerve and on the olfactory receptor neurons (ORNs) commencing with the
      earliest olfactory axon outgrowth (E12-E15). Their expression patterns suggest
      that both NCAM and L1 are associated with extension and fasciculation of
      olfactory axons. A comparison of L1 and olfactory marker protein suggests that L1
      is expressed predominantly on immature ORNs. Laminin has an unique punctate
      staining pattern in the developing olfactory pathway as early as E12. These
      laminin puncta might play a role in olfactory neurite outgrowth and guidance. At
      E14, when pioneer olfactory axons enter the brain, the laminin-positive meninges
      on the surface of the olfactory bulb primordium break down but remain intact in
      the rest of the telencephalon. This suggests a functional interaction between the
      olfactory axons and the glial-pial barrier. Fibronectin staining is diffuse
      throughout the cranial mesenchyme but is absent from the olfactory nerve pathway.
      No specific patterns of tenascin or chondroitin sulfate, were observed during
      early olfactory development. PNA binding sites were associated with olfactory
      axon fasciculation. The expression of several extracellular matrix molecules and
      cell surface molecules is spatially and temporally regulated in the developing
      olfactory system. These molecules, thus, may play functional roles in olfactory
      axon outgrowth, fasciculation, and/or guidance.

PMID- 8866843
TI  - A calbindin-immunoreactive cone bipolar cell type in the rabbit retina.
AB  - We have studied the distribution of the calcium-binding protein calbindin in the
      adult rabbit retina by using a commercially available antibody and
      immunocytochemical methods. The most heavily labeled cells are A-type horizontal
      cells, but B-type horizontal cells are also lightly labeled by this antibody.
      Among the horizontal cells, there is a mosaic of small, well-labeled somata,
      which we have identified as a subset of ON cone bipolar cells. In addition, some
      wide-field amacrine cells and a few large ganglion cells are also labeled for
      calbindin. The calbindin bipolar cells form a regular mosaic with a peak density
      of approximately 1,700 cells/mm2, falling to 550 cells/mm2 in the periphery. They
      account for about one-twelfth of cone bipolar cells, and they are narrowly
      stratified deep in sublamina 4 of the inner plexiform layer immediately above the
      rod bipolar terminals. Double-label experiments using an antibody to protein
      kinase C (PKC) indicate that the calbindin bipolar cells are completely distinct
      from the population of rod bipolar cells. Rod bipolar cells outnumber the
      calbindin cone bipolar cells by a factor of four to five. Further double-label
      experiments show that the calbindin bipolar cells are also labeled for recoverin.
      The calbindin bipolar cells are well coupled to AII amacrine cells, and they
      account for roughly 23% of the AII coupled bipolar cells. This suggests that
      there are three to four additional ON cone bipolar cell types that are coupled to
      AII amacrine cells. The calbindin cone bipolar cell described in this paper
      shares many characteristics with a reconstructed cone bipolar cell that forms the
      most gap junctions with AII amacrine cells (Strettoi et al. [1994] J. Comp.
      Neurol. 347:139-149). We conclude that these different methodologies provide
      complementary descriptions of the same cone bipolar cell type. The calbindin
      antibody defines a subset of cone bipolar cells in the rabbit retina. The cells
      in this subset are almost certainly the deepest of the cone bipolar cells. The
      tight stratification of the calbindin cone bipolar cell suggests that the inner
      plexiform layer is stratified according to depth, with narrow functional
      divisions within the broad partition of sublamina b, where ON signals are
      processed. The strength of coupling between the calbindin cone bipolar cells and
      AII amacrine cells suggests this pathway plays a major role under scotopic
      conditions.

PMID- 8866844
TI  - Chondroitin sulfate proteoglycans in the developing central nervous system. I.
      cellular sites of synthesis of neurocan and phosphacan.
AB  - We have used in situ hybridization histochemistry to examine the cellular sites
      of synthesis of two major nervous tissue proteoglycans, neurocan and phosphacan,
      in embryonic and postnatal rat brain and spinal cord. Both proteoglycans were
      detected only in nervous tissue. Neurocan mRNA was evident in neurons, including
      cerebellar granule cells and Purkinje cells, and in neurons of the hippocampal
      formation and cerebellar nuclei. In contrast, phosphacan message was detected
      only in astroglia, such as the Golgi epithelial cells of the cerebellum. At
      embryonic day 13-16, phosphacan mRNA is largely confined to areas of active cell
      proliferation (e.g., the ventricular zone of the ganglionic eminence and septal
      area of the brain and the ependymal layer surrounding the central canal of the
      spinal cord) as well as being present in the roof plate. The distribution of
      neurocan message is more widespread, extending to the cortex, hippocampal
      formation, caudate putamen, and basal telencephalic neuroepithelium, and neurocan
      mRNA is present in both the ependymal and mantle layers of the spinal cord but
      not in the roof plate. The presence of neurocan mRNA in areas where the
      proteoglycan is not expressed suggests that the short open reading frame in the
      5'-leader of neurocan may function as a cis-acting regulatory signal for the
      modulation of neurocan expression in the developing central nervous system.

PMID- 8866845
TI  - Chondroitin sulfate proteoglycans in the developing central nervous system. II.
      Immunocytochemical localization of neurocan and phosphacan.
AB  - Using immunocytochemistry, we have compared the distribution of neurocan and
      phosphacan in the developing central nervous system. At embryonic day 13 (E13),
      phosphacan surrounds the radially oriented neuroepithelial cells of the
      telencephalon, whereas neurocan staining of brain parenchyma is very weak. By E16
      19, strong staining of both neurocan and phosphacan is seen in the marginal zone
      and subplate of the neocortex, and phosphacan is present in the ventricular zone
      and also has a diffuse distribution in other brain areas. Phosphacan is also
      widely distributed in embryonic spinal cord, where it is strongly expressed
      throughout the gray and white matter, in the dorsal and ventral nerve roots, and
      in the roof plate at E13, when neurocan immunoreactivity is seen only in the
      mesenchyme of the future spinal canal. Neurocan first begins to appear in the
      spinal cord at E16-19, in the region of ventral motor neurons. In early postnatal
      and adult cerebellum, neurocan immunoreactivity is seen in the prospective white
      matter and in the granule cell, Purkinje cell, and molecular layers, whereas
      phosphacan immunoreactivity is associated with Bergmann glial fibers in the
      molecular layer and their cell bodies (the Golgi epithelial cells) below the
      Purkinje cells. These immunocytochemical results demonstrate that the expression
      of neurocan and phosphacan follow different developmental time courses not only
      in postnatal brain (as previously demonstrated by radioimmunoassay) but also in
      the embryonic central nervous system. The specific localization and different
      temporal expression patterns of these two proteoglycans are consistent with other
      evidence indicating that they have overlapping or complementary roles in axon
      guidance, cell interactions, and neurite outgrowth during nervous tissue
      histogenesis.

PMID- 8866846
TI  - Comparison of photoreceptor spatial density and ganglion cell morphology in the
      retina of human, macaque monkey, cat, and the marmoset Callithrix jacchus.
AB  - We studied the relationship between the morphology of ganglion cells and the
      spatial density of photoreceptors in the retina of two Old World primates, human
      and macaque monkey; the diurnal New World marmoset Callithrix jacchus; and the
      cat. Ganglion cells in macaque and marmoset were labelled by intracellular
      injection with Neurobiotin or by DiI diffusion labelling in fixed tissue. Cone
      photoreceptor densities were measured from the same retinas. Supplemental data
      for macaque and data for human and cat were taken from published studies. For the
      primates studied, the central retina is characterised by a constant numerical
      convergence of cones to ganglion cells. Midget ganglion cells derive their input,
      via a midget bipolar cell, from a single cone. Parasol cells derive their input
      from 40-140 cones. Outside the central retina, the convergence increases with
      eccentricity. The convergence to beta cells in the cat retina is very close to
      that for parasol cells in primate retina. The convergence of rod photoreceptors
      to ganglion cells is similar in human, macaque, and marmoset, with parasol cells
      receiving input from 10-15 times more rods than midget cells. The low convergence
      of cones to midget cells in human and macaque retinas is associated with
      distinctive dendritic "clusters" in midget cells' dendritic fields. Convergence
      in marmoset is higher, and the clusters are absent. We conclude that the
      complementary changes in photoreceptor density and ganglion cell morphology
      should be considered when forming linking hypotheses between dendritic field,
      receptive field, and psychophysical properties of primate vision.

PMID- 8866847
TI  - Morphology of retinal ganglion cells in a new world monkey, the marmoset
      Callithrix jacchus.
AB  - We studied the morphology of retinal ganglion cells in a diurnal New World
      primate, the marmoset Callithrix jacchus. This species is of interest as a model
      for primate vision because it has good behavioural visual acuity, and the retina
      and subcortical visual pathways are very similar to those of Old World monkeys
      and humans. Ganglion cells were labelled by placing small crystals of the
      carbocyanin dye DiI into the optic fibre layer, or by intracellular injection of
      neurobiotin. Two main classes of ganglion cell were labelled. We call these Group
      A cells and Group B cells: they are respectively homologous to parasol and midget
      cell classes. Group A and Group B cells show similar patterns of dye coupling,
      dendritic stratification and dendritic field size as their counterparts in Old
      World monkeys and humans. A third group of cells, which we call Group C, is
      morphologically heterogeneous. Examples corresponding to wide-field ganglion cell
      types described in Old World primates were encountered. One subgroup of C cells
      has a morphology very similar to that of the small bistratified (blue-on) cell
      described in macaque retina, suggesting that this functional pathway is common to
      all primates. As for other New World monkeys, the marmoset shows a sex-linked
      polymorphism of cone pigment expression, such that all males are dichromats and
      the majority of females are trichromats. No systematic differences in Group B
      cells were seen between male and female retinas, suggesting that trichromacy is
      not accompanied by specific changes in ganglion cell morphology.

PMID- 8866848
TI  - Comparative morphology of three types of projection-identified pyramidal neurons
      in the superficial layers of cat visual cortex.
AB  - The morphology and dendritic organization of corticocortical neurons in the
      superficial layers of area 18 that project to area 17 were studied by
      intracellular injection of lucifer yellow in the fixed-slice preparation. This
      corticocortical population contains primarily standard pyramidal cells, but
      occasional nonpyramidal, modified, fusiform, star, and inverted pyramidal cells
      were also seen. All cell types were present throughout layer 2 and in the upper
      and middle parts of layer 3. Standard pyramidal cells were found exclusively in
      lower layer 3. The mean somatic area of the area 17 projecting neurons was 251
      microns 2. The width of basal dendritic fields was correlated to cell size for
      standard pyramidal cells but not for the other cell types. Next, the morphology
      and dendritic organization of the area 17 projecting neurons were compared to the
      pyramidal cells of the local horizontal patch networks and of the callosal
      system. The depth profile of the area 17 projecting and callosal pyramidal groups
      was virtually identical, peaking at 400 microns from the pial surface, whereas
      the local patch pyramidal group peaked at 281 microns. The local patch, area 17
      projecting, and callosal pyramidal cells displayed increasingly larger mean
      somatic areas and basilar dendritic field width measurements. The number of basal
      dendritic branch points was greatest for callosal cells, and it was
      indistinguishable between local patch and area 17 projecting neurons. In the
      tangential plane, circular dendritic fields were observed on all callosal cells,
      but they were found on only approximately half of the local patch and area 17
      projecting neurons. The remaining local patch and area 17 projecting neurons
      displayed mediolaterally and anteroposteriorly elongated basal dendritic fields,
      respectively.

PMID- 8866849
TI  - Topography, architecture, and connections of somatosensory cortex in opossums:
      evidence for five somatosensory areas.
AB  - Microelectrode maps of somatosensory inputs were related to cortical architecture
      and patterns of cortical connections to provide evidence for five subdivisions of
      the somatosensory or sensorimotor cortex in North American opossums (Didelphis
      marsupialis). Microelectrode recordings revealed three systematic representations
      of the body surface. A large mediolaterally oriented representation was
      identified as the primary somatosensory area (S1) by its relative position,
      somatotopy, architecture, and connections. S1 represented the hindlimb, trunk,
      forelimb, and face in a mediolateral sequence. Two additional representations of
      cutaneous receptors were found caudolateral to S1, each with face representations
      adjacent to the border of lateral S1 and other body-part representations
      progressing more caudally toward the auditory cortex. We identified the more
      dorsal field as the second somatosensory area (S2) and the more ventral field as
      the parietal ventral area (PV). Tracers injected into S1 labeled neurons and
      terminals in architectonically distinct fields rostral and caudal to S1, the
      somatosensory caudal area (SC) and the somatosensory rostral area (SR). Movements
      could be evoked by microstimulation from sites scattered over S1, SR, and the
      frontal cortex, but thresholds were high and uncharacteristic of motor cortex. S2
      and PV merged caudally with the cortex responsive to auditory stimuli, possibly
      A1, and neurons in some caudal recording sites in PV were activated by both
      auditory and cutaneous stimuli. Primary (V1) and secondary (V2) visual areas were
      also identified by microelectrode mapping, architecture, and connections. In
      addition, at least part of the cortex between V2 and the somatosensory cortex had
      visual connections. Thus, most of the dorsolateral cortex of opossums appears to
      be somatosensory, auditory, or visual.

PMID- 8866850
TI  - Immunohistochemical localization of neurotransmitters utilized by neurons in the
      rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) that
      project to the oculomotor and trochlear nuclei in the cat.
AB  - The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
      contains excitatory and inhibitory burst neurons that are related to the control
      of vertical and torsional eye movements. In the present study, light microscopic
      examination of the immunohistochemical localization of amino acid
      neurotransmitters demonstrated that the riMLF in the cat contains overlapping
      populations of neurons that are immunoreactive to the putative inhibitory
      neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory
      neurotransmitters glutamate and aspartate. By using a double-labelling paradigm,
      GABA-, glutamate-, and aspartate-immunoreactive neurons in the riMLF were
      retrogradely labelled by transport of horseradish peroxidase (HRP) from the
      oculomotor and trochlear nuclei. Electron microscopy showed that the oculomotor
      and trochlear nuclei contain synaptic endings that are immunoreactive to GABA,
      glutamate, or aspartate. Each neurotransmitter-specific population of synaptic
      endings has distinctive ultrastructural and synaptic features. Synaptic endings
      in the oculomotor and trochlear nuclei that are anterogradely labelled by
      transport of biocytin from the riMLF are immunoreactive to GABA, glutamate, or
      aspartate. Taken together, the findings from these complimentary retrograde and
      anterograde double-labelling studies provide rather conclusive evidence that GABA
      is the inhibitory neurotransmitter, and glutamate and aspartate are the
      excitatory neurotransmitters, utilized by premotor neurons in the riMLF that are
      related to the control of vertical saccadic eye movements.

PMID- 8866851
TI  - Morphology and soma-dendritic distribution of synaptic endings from the rostral
      interstitial nucleus of the medial longitudinal fasciculus (riMLF) on motoneurons
      in the oculomotor and trochlear nuclei in the cat.
AB  - The morphology and soma-dendritic distribution of anterograde biocytin-labelled
      rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
      synaptic endings in the oculomotor and trochlear nuclei have been examined by
      electron microscopy by using both preembedding immunoperoxidase and postembedding
      immunogold methods. The results indicate that three morphological types of riMLF
      synaptic endings are distinguishable on the basis of synaptic vesicle morphology
      (spheroidal, pleiomorphic, or ellipsoidal) and postsynaptic membrane
      specializations (asymmetrical or symmetrical). All three morphological types of
      riMLF synaptic endings establish synaptic connections predominantly with
      dendrites. Synaptic endings that contain ellipsoidal synaptic vesicles have a
      more proximal soma-dendritic distribution than those that contain either
      spheroidal or pleiomorphic synaptic vesicles. Furthermore, all three
      morphological types of synaptic endings are encountered in the same motoneuron
      subdivisions of the oculomotor and trochlear nuclei in the same experiments. The
      findings suggest that subregions of the riMLF contain coexistent populations of
      excitatory and inhibitory premotor neurons that are related to opposite
      directions of vertical saccadic eye movements but that project to the same
      motoneuron subgroups on the ipsilateral side. Both the morphology and the mode,
      pattern, and soma-dendritic distribution of saccade-related riMLF synaptic
      endings that establish synaptic connections with vertical motoneurons differ from
      those of excitatory and inhibitory second-order vertical vestibular synaptic
      endings. These differences in the synaptic organization of riMLF and second-order
      vestibular inputs to oculomotor and trochlear motoneurons may be related to
      differences in the information transferred by each source, the riMLF input
      conveying eye-velocity signals, and the vestibular input conveying eye-position
      signals.

PMID- 8866852
TI  - Spatial organization of premotor neurons related to vertical upward and downward
      saccadic eye movements in the rostral interstitial nucleus of the medial
      longitudinal fasciculus (riMLF) in the cat.
AB  - The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
      contains premotor neurons that are related to the control of vertical and
      torsional saccadic eye movements. In the present study, complimentary light
      microscopic anterograde biocytin and retrograde horseradish peroxidase
      experiments have been performed to determine the organization of premotor neurons
      in the riMLF in the cat that are related intimately to the vertical motoneuron
      populations in the oculomotor and trochlear nuclei. The results indicate a
      rostral-caudal topographic arrangement of neurons in the riMLF that is related to
      the target projections to vertical downward (inferior rectus and superior
      oblique) and vertical upward (superior rectus and inferior oblique) motoneurons,
      respectively, in the oculomotor and trochlear nuclei. Both the anterograde and
      the retrograde studies are consistent, in that they demonstrate the tendency for
      downward and upward riMLF neurons to be separated spatially by a distance of
      approximately 0.5 mm in the rostral-caudal axis of the nucleus. The riMLF
      projections to inferior oblique and superior oblique motoneurons are
      predominantly ipsilateral. Projections to inferior rectus and superior rectus
      motoneurons, however, are bilateral, and, presumably, they provide one means for
      assuring the conjugacy of vertical saccadic eye movements. Because premotor burst
      neurons that encode parameters for upward or downward saccades are intermingled
      within the riMLF, and excitatory and inhibitory premotor neurons also coexist in
      this region, the findings from this study suggest that subregions of the riMLF
      contain coexistent populations of excitatory and inhibitory neurons that are
      related to opposite directions of vertical eye movements. The spatial segregation
      of excitatory premotor neurons in the riMLF that are related to vertical upward
      vs. downward movements, furthermore, provides a basis for the interpretation of
      vertical upward and/or downward gaze palsies that might result from discrete
      lesions at the mesodiencephalic junction in humans.

PMID- 8866853
TI  - NADPH-diaphorase-positive ganglion cells of the rat adrenal gland: age- and sex
      related changes in their number, size, and distribution.
AB  - The rat adrenal gland contains ganglion cells able to synthesize nitric oxide
      (NO). This messenger molecule controls and modulates adrenal secretory activity
      and blood flow. The present study analyzed the number, size, and distribution of
      NO-producing adrenal neurons in adulthood and during postnatal development by
      means of beta-nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)
      histochemistry. This method reliably visualizes the enzyme responsible for NO
      generation. The reactive neurons per adrenal gland were 350-400 in both male and
      female adult rats. The positive nerve cell bodies were mostly located in the
      medulla, few being detected within the cortex and the subcapsular region. Dual
      labeling with anti-microtubule-associated protein 2 antibody, specific for
      neuronal elements, confirmed this distribution. Anti-microtubule-associated
      protein 1b antibody identified a subset of NADPH-d-positive neurons, displaying
      different degrees of maturation according to their position within the adrenal
      gland. At birth, there were about 220 NADPH-d-labeled neurons per adrenal gland
      in both sexes. As confirmed by dual immunocytochemical labeling, their great
      majority was evenly distributed between the cortex and the subcapsular region,
      the medulla being practically devoid of stained neurons. After birth, the number
      of adrenal NADPH-d-positive ganglion cells displayed a strong postnatal increase
      and reached the adult-like distribution after 1-2 months. During the period of
      increase, there was a transient difference in the numbers of these cells in the
      two sexes. Thus we present here evidence of plasticity in the number, size, and
      distribution of NADPH-d-positive adrenal neurons between birth and adulthood; in
      addition, we describe transient sex-related differences in their number and
      distribution during the 2nd postnatal week, which are possibly related to the
      epigenetic action of gonadal hormones during this period.

PMID- 8866854
TI  - ATP-activated cation conductance in a Xenopus renal epithelial cell line.
AB  - 1. Using a whole-cell voltage-clamp technique and fura-2 fluorescence
      measurements, the actions of extracellular adenosine 5'-triphosphate (ATP) in
      single cells of an epithelial cell line (A6), were investigated. 2. ATP (0.1-1000
      microM) induced currents in cells held under voltage clamp. The sequence of
      purinergic agonist potency in activating the currents (2-methylthio ATP >
      adenosine 5'-diphosphate (ADP) > ATP > alpha, beta-methylene ATP) was consistent
      with that of P2y receptors. 3. Reversal potentials (Erev) of the currents under
      various ionic conditions suggest that potassium channels and non-selective cation
      channels were responsible for the ATP-activated conductance, which was permeable
      to calcium. 4. ATP activated the currents in a calcium-free extracellular
      solution. In the presence of extracellular calcium, the currents were completely
      inhibited with 10 mM EGTA in the pipette. 5. ATP (10 microM) increased the
      intracellular calcium concentration ([Ca2+]i) whether cells were bathed in a
      solution containing calcium or not. 6. These results indicate that ATP evoked a
      calcium-dependent cation conductance, permeable to calcium, through P2y receptors
      by releasing calcium from intracellular stores in A6 cells.

PMID- 8866855
TI  - Intracellular sodium homeostasis in rat hippocampal astrocytes.
AB  - 1. We determined the intracellular Na+ concentration ([Na+]i) and mechanisms of
      its regulation in cultured rat hippocampal astrocytes using fluorescence ratio
      imaging of the Na+ indicator SBFI-AM (acetoxymethylester of sodium-binding
      benzofuran isophthalate, 10 microM). Dye signal calibration within the astrocytes
      showed that the ratiometric dye signal changed monotonically with changes in
      [Na+]i from 0 to 140 nM. The K+ sensitivity of the dye was negligible;
      intracellular pH changes, however, slightly affected the 'Na+' signal. 2.
      Baseline [Na+]i was 14.6 +/- 4.9 mM (mean +/- S.D.) in CO2/HCO3(-)-containing
      saline with 3 mM K+. Removal of extracellular Na+ decreased [Na+]i in two phases:
      a rapid phase of [Na+]i reduction (0.58 +/- 0.32 mM min-1) followed by a slower
      phase (0.15 +/- 0.09 mM min-1). 3. Changing from CO2/HCO3(-)-free to CO2/HCO3(-)
      buffered saline resulted in a transient increase in [Na+]i of approximately 5 mM,
      suggesting activation of inward Na(+)-HCO3- cotransport by CO2/HCO3-. During
      furosemide (frusemide, 1 mM) or bumetanide (50 microM) application, a slow
      decrease in [Na+]i of approximately 2 mM was observed, indicating a steady inward
      transport of Na+ via Na(+)-K(+)-2Cl- cotransport under control conditions.
      Tetrodotoxin (100 microM) did not influence [Na+]i in the majority of cells
      (85%), suggesting that influx of Na+ through voltage-gated Na+ channels
      contributed to baseline [Na+]i in only a small subpopulation of hippocampal
      astrocytes. 4. Blocking Na+, K(+)-ATPase activity with cardiac glycosides
      (ouabain or strophanthidin, 1 mM) or removal of extracellular K+ led to an
      increase in [Na+]i of about 2 and 4 mM min-1, respectively. This indicated that
      Na+, K(+)-ATPase activity was critical in maintaining low [Na+]i in the face of a
      steep electrochemical gradient, which would favour a much higher [Na+]i. 5.
      Elevation of extracellular K+ concentration ([K+]o) by as little as 1 mM (from 3
      to 4 mM) resulted in a rapid and reversible decrease in [Na+]i. Both the slope
      and the amplitude of the [K+]o-induced reductions in [Na+]i were sensitive to
      bumetanide. A reduction of [K+]o by 1 mM increased [Na+]i by 3.0 +/- 2.3 mM. In
      contrast, changing extracellular Na+ concentration by 20 mM resulted in changes
      in [Na+]i of less than 3 mM. 6. These results implied that in hippocampal
      astrocytes low baseline [Na+]i is determined by the action of Na(+)-HCO3-
      cotransport, Na(+)-K(+)-2Cl- cotransport and Na+, K(+)-ATPase, and that both Na+,
      K(+)-ATPase and inward Na(+)-K(+)-2Cl cotransport are activated by small,
      physiologically relevant increases in [K+]o. These mechanisms are well suited to
      help buffer increases in [K+]o associated with neural activity.

PMID- 8866856
TI  - Cholinergic inhibition of Ca2+ current in guinea-pig gastric and tracheal smooth
      muscle cells.
AB  - 1. Cholinergic regulation of L-type Ca2+ channels was investigated in freshly
      dissociated guinea-pig gastric and tracheal smooth muscle cells. Acetylcholine
      (ACh, 50 microM) decreased Ca2+ channel current (ICa) by 37 +/- 3% (mean +/-
      S.E.M., 46 cells). 2. ACh reduced ICa at all voltages, with no shift in the
      current-voltage relationship. Effects of ACh were rapid (within 5 s) and
      repeatable, with multiple applications reproducibly inhibiting ICa in the
      continued presence of extracellular Ca2+ and in the presence of protein kinase C
      inhibitors. 3. The involvement of Ca2+ stores in this inhibition was investigated
      using Ca(2+)-free solution or cyclopiazonic acid (CPA) to deplete the stores. ACh
      initially inhibited ICa in the Ca(2+)-free solution (Na+ as charge carrier, 53 +/
      4% decrease, 18 cells) with subsequent responses significantly attenuated (n =
      9). CPA (1 microM) reduced, then abolished, the effects of ACh on ICa (n = 5). 4.
      When studied in cell-attached patches (Ba2+ as charge carrier), ACh reduced Ca2+
      channel open probability in twenty-two of thirty-six cells, consistent with the
      involvement of a diffusible cytosolic messenger. 5. ACh also inhibited ICa in
      tracheal muscle cells (reduction of 38 +/- 6% in 1 mM Ca2+, 4 cells; 77 +/- 3% in
      Ca(2+)-free solution, 7 cells). Furthermore, in cells where ACh elicited
      oscillating Ca(2+)-activated Cl- current, oscillatory inhibition of ICa was also
      observed (3 cells). 6. In summary, ACh causes rapid and reversible inhibition of
      ICa in gastric and tracheal muscles. Ca2+ stores were required to initiate this
      effect, with the rapid onset and oscillatory inhibition consistent with Ca2+
      inhibition of the channel. Suppression of ICa would reduce Ca2+ entry during
      cholinergic excitation.

PMID- 8866857
TI  - Facilitation of T-type calcium current in bullfrog atrial cells: voltage
      dependent relief of a G protein inhibitory tone.
AB  - 1. The properties of the low-threshold calcium current, ICa,T, were investigated
      in bullfrog isolated atrial cardiomyocytes using the whole-cell, patch-clamp
      technique under control conditions and during beta-adrenergic stimulation. 2. The
      intracellular application of GTP gamma S or adenosine-5'-O-3-thiotriphosphate
      (ATP gamma S), poorly hydrolysable analogues of GTP and ATP, respectively, barely
      affected ICa,T amplitude in control conditions. beta-Adrenergic stimulation
      effects were more marked in the presence of ATP gamma S. 3. The intracellular
      application of GDP beta S and ADP reduced ICa,T amplitude. In cells pretreated
      with pertussis toxin, ICa,T amplitude was significantly increased. In both
      conditions, the addition of isoprenaline was without effect. 4. Under both
      control and beta-adrenergic-stimulated conditions, a conditioning prepulse to +70
      mV did not fully inactivate ICa,T; rather ICa,T facilitation often occurred after
      beta-adrenergic stimulation. 5. In GTP gamma S- and ATP gamma S-dialysed cells,
      ICa,T facilitation was generally observed after a prepulse; it was larger in the
      ATP gamma S dialysis. Facilitation was sustained but ended immediately upon
      cessation of conditioning prepulses. After beta-adrenergic stimulation,
      facilitation was more marked in GTP gamma S- than in ATP gamma S-dialysed cells.
      6. ICa,T facilitation was prevented by the intracellular application of GDP beta
      S and by pertussis toxin pretreatment. 7. ICa,T facilitation developed markedly
      in the presence of intracellular cyclic AMP. This effect was prevented by
      pertussis toxin pretreatment of the cells. 8. It is thus proposed that ICa,T is
      under a double antagonistic control by both a Gs and a Gi protein. Furthermore,
      the double-pulse-induced facilitation of ICa,T results from a voltage-dependent
      relief of the Gi protein inhibitory tone. Such an effect is increased by protein
      kinase A-dependent phosphorylation, presumably of the Gi protein.

PMID- 8866858
TI  - Reopening of single L-type Ca2+ channels in mouse cerebellar granule cells:
      dependence on voltage and ion concentration.
AB  - 1. We recorded the activity of single L-type Ca2+ channels from cell-attached
      patches on mouse cerebellar granule cells. The experiments investigated the
      mechanism of channel reopening at negative membrane potentials following a strong
      depolarization. 2. L-type channels that reopened following a strong
      depolarization showed a wide distribution of single-channel conductances, which
      ranged from 16 to 28 pS in the presence of 90 mM Ba2+. 3. The distribution of the
      latencies before reopening was fitted as the sum of two exponential components
      with time constants tau f approximately 1 and tau s approximately 12 ms at -70
      mV. Hyperpolarization reduced the time constant of the slower component
      approximately e-fold per 43 mV, but had no effect on the faster component. 4.
      Raising the concentration of external Ba2+ reduced the time constant of the
      slower component of the reopening latency without altering the fast component.
      The time constant of the slow component was approximately 27 ms in 10 mM Ba2+ and
      decreased to 12 ms in 90 mM Ba2+ at -70 mV. The relation between the time
      constant and external Ba2+ saturated with an apparent KD of approximately 20 mM.
      5. The distribution of reopening times was best fitted as the sum of two
      exponential components with time constants tau f approximately 0.5 ms and tau s
      approximately 4.5 ms at -70 mV. The conditional latencies before reopening into
      either the short or long open state were indistinguishable. 6. The results are
      consistent with the idea that a positively charged blocker occludes the pore
      during depolarization and channels reopen as the blocker dissociates following
      repolarization to negative potentials.

PMID- 8866859
TI  - Basal responses of the L-type Ca2+ and hyperpolarization-activated currents to
      autonomic agonists in the rabbit sino-atrial node.
AB  - 1. The dose dependence of the cholinergic agonist acetylcholine (ACh) and the
      beta-adrenergic agonist isoprenaline (Iso) were determined for the
      hyperpolarization-activated current (If) and the L-type Ca2+ current (ICa,L) in
      single cells isolated from the rabbit sino-atrial (SA) node. 2. ACh inhibited If
      by a negative shift of its activation curve with a maximal effect of -9.9 mV;
      half-maximal effect was produced by 0.019 microM ACh. High ACh concentrations
      were required to inhibit ICa,L only partially (31% inhibition at 300 microM). 3.
      In contrast, If and ICa,L responded to Iso over a similar dose range, with
      concentrations for half-maximal enhancement of 0.0136 and 0.0070 microM,
      respectively. 4. The effects on spontaneous activity of ACh (range 0.001-0.03
      microM) and Iso (range 0.001-1 microM) were investigated. ACh decreased the slope
      of diastolic depolarization at concentrations similar to those inhibiting If (>
      50% at 0.03 microM). Iso enhanced diastolic depolarization at concentrations
      similar to those affecting both If and ICa,L (half-maximal effect at 0.027
      microM). 5. In a ramp-clamp protocol simulating diastolic depolarization, the
      threshold for activation of inward nifedipine-sensitive current was -41.22 +/-
      0.68 mV. Although enhancing ICa,L, Iso did not affect this threshold. 6. Half
      maximal ACh concentrations for inhibition of automaticity and If are similar and
      are lower than the threshold concentrations for modulation of ICa,L; this argues
      against a role of ICa,L in direct muscarinic modulation of pacemaking. In
      contrast, modulation of If, ICa,L and automaticity occur at similar Iso
      concentrations. The difference between maximum diastolic potential (-61.95 +/-
      0.93 mV) and the threshold for Iso-stimulated ICa,L (-39.54 +/- 1.03 mV) suggests
      that this current plays a role only at later stages of diastolic depolarization.

PMID- 8866860
TI  - Inwardly rectifying K+ channels in freshly dissociated coronary endothelial cells
      from guinea-pig heart.
AB  - 1. Inwardly rectifying K+ (IK(IR)) currents of freshly dissociated coronary
      endothelial cells from guinea-pig heart were investigated with the perforated
      patch technique. 2. The whole-cell current-voltage relationship of endothelial
      cells showed strong inward rectification. Increasing the extracellular K+
      resulted in an increase of inward currents. The slope conductance of the cells in
      the potential range negative to the calculated potassium equilibrium potential
      (EK) with 5, 60 and 150 mM external potassium was 0.18 +/- 0.14, 0.55 +/- 0.50
      and 0.63 +/- 0.29 nS (mean +/- S.D.), respectively. 3. To quantify the steepness
      of inward rectification, the voltage dependence of the chord conductance of the
      cells was fitted with a Boltzmann function. The slope factor k describing the
      steepness of the relationship was 6.8 +/- 1.5 mV. 4. Extracellular barium induced
      a potential- and time-dependent block of inward currents through endothelial KIR
      channels. Half-maximum inhibition of IK(IR) currents was achieved with < or = 1
      microM barium at a membrane potential of -70 mV in a solution containing 60 mM
      K+. 5. Whole-cell inward currents revealed the opening and closing of single KIR
      channels. The single-channel conductance was 26 +/- 3 pS with 60 mM external K+
      and 33 +/- 6 pS with 150 mM external K+. 6. Our results suggest that the
      electrical properties of freshly dissociated endothelial cells are to a large
      extent determined by five to sixty active strong inwardly rectifying K+ (KIR)
      channels.

PMID- 8866861
TI  - The tetravalent organic cation spermine causes the gating of the IRK1 channel
      expressed in murine fibroblast cells.
AB  - 1. The activation kinetics of the IRK1 channel stably expressed in L cells (a
      murine fibroblast cell line) were studied under the whole-cell voltage clamp.
      Without polyamines or Mg2+ in the pipettes, inward currents showed an exponential
      activation on hyperpolarization. The steep inward rectification of the currents
      around the reversal potential (Erev) could be described by the open-close
      transition of the channel with first-order kinetics. 2. When the tetravalent
      organic cation spermine (Spm) was added in the pipettes, the activation kinetics
      changed; this was explicable by the increase in the closing rate constant. The
      activation of the currents observed without Spm or Mg2+ in the pipettes was
      ascribed to the unblocking of the 'endogenous-Spm block'. 3. In the presence of
      the divalent cation putrescine (Put) or of Mg2+ in the pipettes, a different non
      conductive state suppressed the outward currents on depolarization; the channels
      instantaneously changed to the open state on repolarization. As the
      depolarization was prolonged, this non-conductive state was replaced by the non
      conductive state that shows an exponential activation on repolarization. This
      phenomenon was attributed to the redistribution of the channels from the Put- or
      Mg(2+)-blocked state to the 'endogenous Spm-blocked state' during depolarization.
      4. In the presence of the trivalent cation spermidine (Spd) in the pipettes, two
      different non-conductive states occurred, showing a faster and a slower
      activation on repolarization. The rectification around Erev was mainly due to the
      non-conductive state showing a faster activation, which appeared to be the Spd
      blocked state. During depolarization, redistribution of the channels to the
      'endogenous Spm-blocked state' also occurred. 5. In the presence of Spd, Put or
      Mg2+ in the pipettes, the voltage dependence of the activation time constant
      reflecting the unblocking of the 'endogenous Spm' was shifted in the
      hyperpolarizing direction. 6. Our results suggest that the 'intrinsic gating'
      that shows the time-dependent activation on repolarization, and that is
      responsible for the inward rectification around Erev, reflects the blocking
      kinetics of the tetravalent Spm.

PMID- 8866862
TI  - Mechanism of inhibition of delayed rectifier K+ current by 4-aminopyridine in
      rabbit coronary myocytes.
AB  - 1. The mechanisms involved in the 4-aminopyridine (4-AP)-induced block of delayed
      rectifier K+ current (IK(V)) in vascular smooth muscle cells were studied in
      cells enzymatically isolated from the rabbit coronary artery. 2. 4-AP inhibited
      slowly inactivating IK(V) in a dose-dependent manner (concentration producing
      half-maximal inhibition, K1/2, = 1.37 mM), and shifted the steady-state
      activation and inactivation curves of IK(V) by +9 and +16 mV, respectively. 3.
      The time constant of activation was significantly increased by 4-AP at +20 mV;
      deactivation kinetics were unaffected upon repolarization to -40 mV. The fast
      (tau f approximately 1 s) and slow (tau s approximately 5 s) time constants of
      inactivation (0 and +20 mV), and the recovery kinetics (tau r approximately 6 s)
      at -60 mV were not significantly affected by 0.5 mM 4-AP. However, tau f
      disappeared in the presence of 2 mM 4-AP while tau s remained unaffected. 4. Use
      dependent unblock of IK(V) was revealed at potentials > or = -10 mV from analyses
      of the voltage dependence of 4-AP-sensitive currents and the frequency-dependent
      changes ('reverse use dependence') of IK(V) during the application of repetitive
      steps (-60 to +20 mV for 250 ms at a rate of 0.25 Hz) in control conditions, in
      the presence of 0.5 mM 4-AP, and after washout of the drug. These results
      suggested that 4-AP preferentially binds to the channel in the closed state, and
      unbinding is promoted by transitions to the open state. 5. The channel was
      modelled as a simple three-state mathematical loop model incorporating single
      closed, open and inactivated states. The block by 4-AP was modelled as a state
      dependent interaction with 4-AP primarily binding to the closed state. Computer
      simulations support the hypothesis that 4-AP-induced block of the delayed
      rectifier K+ (KV) channel in the closed state is relieved during membrane
      depolarization. 6. Closed state binding of 4-AP to the KV channel depolarizes
      vascular smooth muscle cells by shifting the activation curve of these channels
      to more positive potentials.

PMID- 8866863
TI  - A non-inactivating K+ current sensitive to muscarinic receptor activation in rat
      cultured cerebellar granule neurons.
AB  - 1. Whole-cell recordings were made from cultured cerebellar granule neurons using
      perforated patch clamp techniques. The primary cultures were prepared using 6- to
      9-day-old Sprague-Dawley rats. 2. Neurons in culture for less than 48 h possessed
      resting membrane potentials of -29 mV. However, neurons in culture for 7 days had
      much more hyperpolarized resting membrane potentials (-89 mV). Over the same
      period, these neurons developed an additional component of outward current. 3.
      This non-inactivating current was activated by depolarization, exhibited outward
      rectification and reversed close to the potassium equilibrium potential. The
      kinetics of activation and deactivation were very rapid. 4. Muscarine ((+)
      muscarine chloride) reversibly inhibited the current with an EC50 of 0.17 microM.
      The inhibition by muscarine was unaffected by pre-incubation for 17-20 h with 120
      micrograms ml-1 pertussis toxin. 5. The current and its inhibition by muscarine
      were unaffected by 100 microM Cd2+. In Ca(2+)-free conditions, the current was
      significantly larger than in 0.5 mM Ca2+, but inhibition by 10 microM muscarine
      was significantly reduced. 6. The standing outward current was not obviously
      affected by 50 microM 5-HT, 50 microM noradrenaline, 50 microM 2-chloroadenosine
      or 5 mM tetraethylammonium. It was reduced by 10 microM La3+, 10 microM Zn2+ and
      1 mM Ba2+. 7. Muscarinic agonists increased the input resistance of neurons and
      shifted the zero current level in the depolarized direction when voltage clamped.
      This enhanced excitability was evident under current clamp, where 10 microM
      muscarine depolarized granule neurons such that action potentials became evident.

PMID- 8866864
TI  - Presynaptic muscarinic inhibition in bullfrog sympathetic ganglia.
AB  - 1. Muscarinic modulation of nicotinic transmission was studied in bullfrog
      sympathetic ganglia by recording synaptic currents from B and C neurones. 2. Bath
      applied muscarine reduced the amplitude of EPSCs recorded at < 0.2 Hz from B
      neurones by up to 57%. The action was reversible, showed no apparent
      desensitization, and had an EC50 of 102 nM. Muscarine had no effect on EPSCs in C
      neurones. 3. Currents evoked by ionophoretic application of ACh to B neurones
      were unchanged by muscarine. Muscarine increased the coefficient of variation
      (c.v.) of EPSC amplitude. The effect upon the ratio of c.v.2control to
      c.v.2muscarine was proportional to the change in mean EPSC amplitude. 4.
      Activation of muscarinic receptors by ACh from nerve terminals was observed by
      comparing trains of EPSCs in normal Ringer solution and atropine. Inhibition of
      EPSC amplitude by 15-40% was seen as frequency was increased from 1 to 5 Hz. The
      minimal latency for onset of inhibition was approximately 2 s. Stimulation at 20
      Hz did not produce inhibition. 5. The results indicate that presynaptic
      muscarinic receptors are selectively expressed by a functional subclass of
      preganglionic sympathetic nerve terminals. Physiological activation of the
      receptors occurs during repetitive activity. The extent of autoreceptor-mediated
      inhibition varies as a biphasic function of stimulus frequency.

PMID- 8866865
TI  - KCl cotransport activation in human erythrocytes by high hydrostatic pressure.
AB  - 1. Pressure induced a 4- to 5-fold stimulation of the residual (i.e. oubain
      bumetanide insensitive) 86Rb+ influx across the human red cell membrane. This
      enhancement showed a broad pHo dependence with a maximum stimulation around pHo
      7. 2. At atmospheric pressure, the protein kinase inhibitors staurosporine and
      chelerythrine stimulated a normally silent component of 86Rb+ influx in a dose
      dependent manner with a half-maximum stimulatory concentration at about 550 nM
      and 140 microM, respectively. The component stimulated by staurosporine was
      entirely Cl- dependent, but part of the chelerythrine effect was Cl- independent.
      3. Staurosporine (3 microM), chelerythrine (200 microM) and N-ethylmaleimide (1
      mM) stimulated further the increased residual 86Rb+ influx in cells at high
      pressure. 4. The serine/threonine protein phosphatase inhibitors okadaic acid,
      cantharidin and calyculin A inhibited the stimulatory pressure effect in a dose
      dependent manner with half-maximum inhibitory concentrations of 70 nM, 2.5 microM
      and 3.3 nM, respectively. In contrast, deltamethrin, a specific protein
      phosphatase type 2B inhibitor, did not affect the stimulation by pressure, up to
      a concentration of 10 microM. 5. Decreasing the internal ionized magnesium
      concentration ([Mg2+]i) with A23187 and EDTA stimulated the increased residual
      86Rb+ influx in cells at high pressure. On the other hand, increasing the [Mg2+]i
      nearly abolished the stimulatory pressure effect. 6. Decreasing the [Mg2+]i
      produced a marked change in the pHo dependence curve, with a linear increase of
      the 86Rb+ influx at higher pHo values. 7. We demonstrate that high pressure
      stimulates the normally silent component of 86Rb+ influx by modifying the
      phosphorylation/dephosphorylation ratio of the KCl cotransporter.

PMID- 8866866
TI  - Modulation by opioid peptides of mechanosensory pathways supplying the guinea-pig
      inferior mesenteric ganglion.
AB  - 1. Radioimmunological techniques were used in isolated guinea-pig inferior
      mesenteric ganglion (IMG)-colon preparations to determine whether opioid peptides
      and neurotensin8-13 (NT8-13), the C-terminal region of NT1-13 recognized by
      neurotensin receptors, modulate distension-induced release of substance P (SP)-
      and vasoactive intestinal polypeptide (VIP)-like immunoreactive (LI) material. 2.
      Colonic distension significantly increased the amount of SP- and VIP-LI material
      released in the ganglionic superfusate. A low-Ca2+ (0.1 mM), high-Mg2+ (15 mM)
      solution blocked their release. 3. In vivo capsaicin pretreatment abolished
      release of SP-LI material during colonic distension but had no significant effect
      on distension-induced release of VIP-LI material. 4. The addition of
      [Leu5]enkephalin, [Met5]enkephalin, PL017 (a mu-receptor agonist) and DPDPE (a
      delta-receptor agonist) to the ganglion side of a two-compartment chamber blocked
      distension-induced release of SP-LI material. The addition of naloxone and ICI
      174,864 (a delta-receptor antagonist) to the ganglion compartment reversed the
      inhibitory effect of the mu- and delta-receptor agonists. 5. Addition of
      [Leu5]enkephalin and [Met5]enkephalin to the ganglion compartment had no
      significant effect on release of VIP-LI material during colonic distension. 6.
      Addition of NT8-13 to the ganglion compartment significantly increased in the
      amount of SP-LI material released during colonic distension but had no affect on
      distension-induced release of VIP-LI material. 7. The results suggest the
      hypothesis that under in vivo conditions, enkephalinergic nerves decrease and
      neurotensinergic nerves increase the release of SP from peripheral branches of
      primary afferent sensory nerves.

PMID- 8866867
TI  - Phospholipase A2 and protein kinase C contribute to myofilament sensitization to
      5-HT in the rabbit mesenteric artery.
AB  - 1. Calcium (Ca2+, 0.1-100 microM) stimulated concentration-dependent contractions
      in small strips from the rabbit mesenteric artery in which the smooth muscle
      cells had been permeabilized with Staphylococcus aureus alpha-toxin. 2. 5
      Hydroxytryptamine (5-HT) and phenylephrine, each in the presence of 10 microM
      guanosine 5'-triphosphate (GTP), concentration-dependently stimulated additional
      contractions in strips sub-maximally contracted by the presence of a buffered
      concentration of calcium (0.3 microM). All the additional contraction was
      abolished with the selective inhibitor of protein kinase C, Ro 31-8220 (10
      microM). 3. Quinacrine (10-50 microM), an inhibitor of phospholipase A2,
      selectively inhibited the sensitization to 5-HT, but did not alter the
      sensitization to either phenylephrine or GTP. 4. Myofilament sensitization to
      calcium was mimicked by exogenous arachidonic acid (300 microM, in the presence
      of indomethacin, miconazole and BW755c) and the stable analogue of arachidonic
      acid, 5,8,11,14-eicosatetrayonic acid (ETYA, 100 microM), and in both cases did
      not require the additional presence of GTP. Ro 31-8220, but not quinacrine,
      reduced the sensitization to arachidonic acid by around 30%. 5. These results
      indicate that G protein-linked myofilament sensitization to calcium in the
      mesenteric artery that follows the activation of 5-HT receptors, but not alpha 1
      receptors, involves phospholipase A2. The sensitization stimulated by each of
      these different receptors, and a component of the response to arachidonic acid,
      also appears to involve the activation of protein kinase C.

PMID- 8866869
TI  - Effects of immunization against an autocrine inhibitor of milk secretion in
      lactating goats.
AB  - 1. Lactating goats were immunized against the goat's milk protein identified as a
      feedback inhibitor of lactation (FIL). Immunization was by three treatments
      during the declining stage of lactation. 2. When antibodies to FIL were
      consistently detected in milk (in response to the third treatment), the rate of
      decline in milk secretion was significantly reduced compared with sham-immunized
      controls. Such a response was not apparent with the first two treatments when
      serum but not milk titres of anti-FIL were raised. 3. When one gland of immunized
      goats was switched (after the third immunization) from twice- to once-daily
      milking, the ipsilateral decrease in the rate of milk secretion was reduced
      significantly compared with sham-immunized goats. 4. The results are compatible
      with the hypothesis that the autocrine agent FIL acts during milk accumulation as
      an inhibitor of milk secretion.

PMID- 8866868
TI  - Minimal role of nitric oxide in basal coronary flow regulation and cardiac
      energetics of blood-perfused isolated canine heart.
AB  - 1. The role of nitric oxide (NO) in the regulation of basal coronary perfusion
      and ventricular chamber energetics was studied in isovolumetrically contracting
      isolated blood-perfused canine hearts. Hearts were cross-perfused by a donor
      animal prior to isolation, and chamber volume controlled by a servo-pump.
      Coronary sinus flow and arterial-coronary sinus oxygen difference were measured
      to determine energetic efficiency. 2. NO synthase (NOS) was competitively
      inhibited by NG-monomethyl-L-arginine (L-NMMA; 0.5 mg kg-1, intracoronary),
      resulting in a reduction of acetylcholine (50 micrograms min-1)-induced flow
      augmentation from 143 to 62% (P < 0.001). 3. NOS inhibition had no significant
      effect on basal coronary flow. Coronary pressure-flow relationships were
      determined at a constant cardiac workload by varying mean perfusion pressure
      between 20 and 150 mmHg. Neither the shape of the relationship, nor the low
      pressure value at which flow regulation was substantially diminished were altered
      by NOS inhibition. 4. Myocardial efficiency was assessed by the relationship
      between myocardial oxygen consumption and total pressure-volume area (PVA), with
      cavity volume altered to generate varying PVAs. This relative load-independent
      measure of energetic efficiency was minimally altered by NOS inhibition. 5. These
      results contrast with isolated crystalloid-perfused heart experiments and suggest
      that in hearts with highly controlled ventricular loading and whole-blood
      perfusion, effects of basal NO production on coronary perfusion and left
      ventricular energetics are minimal.

PMID- 8866870
TI  - Arginine metabolism in cat kidney.
AB  - 1. Arginine is essential for growth in the kitten and, because of the resulting
      hyperammonaemia, in the adult cat an arginine-free diet is life threatening. 2.
      The kidney is the main site of arginine synthesis. 3. This study was performed to
      determine whether the cat kidney synthesizes arginine and to establish which
      factors, such as low citrullinaemia, defects of argininosuccinate synthase and
      lyase activities or high renal arginase activity, might limit renal arginine
      production. 4. Identified nephron segments were isolated by microdissection from
      collagenase-treated cat kidney. 5. Arginine metabolism was studied by incubating
      the nephron segments with either physiological concentrations of L-[ureido
      14C]citrulline (anabolism) or L-[guanido-14C]-arginine (catabolism). Arginine and
      urea were measured by a micro-enzymatic method. Amino acids were measured by
      HPLC. 6. In cat blood, the citrulline, but not the arginine, concentration was
      very low by comparison with other species. 7. Arginine synthesis occurred almost
      entirely in the proximal tubule, the highest rate occurring in the proximal
      convoluted tubule and the lowest in the medullary straight proximal tubule. 8.
      Arginase activity was restricted to the proximal tubule. Urea production
      increased from the convoluted towards the medullary straight tubule. 9. The
      limited capacity of the cat kidney to produce arginine in vivo may result from
      the low blood concentration of citrulline and from the high arginase activity in
      the various proximal cells with the ability to synthesize arginine.

PMID- 8866871
TI  - The role of the renin-angiotensin system in the renal response to moderate
      hypoxia in the rat.
AB  - 1. In two groups of Saffan-anaesthetized rats, we studied the role of the renin
      angiotensin system in mediating the antidiuresis and antinatriuresis induced by
      moderate systemic hypoxia. 2. In both groups, a first period of hypoxia
      (breathing 12% O2 for 20 min) induced a fall in arterial partial pressure of O2
      (Pa,O2; to 42 mmHg), a fall in mean arterial pressure (MABP), no change in renal
      blood flow (RBF) due to an increase in renal vascular conductance (RVC =
      RBF/MABP) and falls in urine flow and absolute sodium excretion (UNaV).
      Concomitantly, plasma renin activity increased from 3.08 +/- 0.68 (mean +/-
      S.E.M.) to 8.36 +/- 1.8 ng ml-1 hr-1. 3. In group 1 (n = 11), Losartan (10 mg kg
      1, I.V.), the angiotensin (AII) AT1 receptor antagonist, induced a fall in MABP
      (115 +/- 3 to 90 +/- 3 mmHg), an increase in RVC such that RBF was unchanged, and
      falls in glomerular filtration rate (GFR), urine flow and UNaV. However, hypoxia
      induced qualitatively similar changes to those seen before Losartan treatment. 4.
      In group 2 (n = 9), we occluded the aorta distal to the renal artery to prevent
      basal MABP and renal perfusion pressure (RPP) from falling after addition of
      Losartan and to keep the hypoxia-induced fall in MABP the same as before Losartan
      treatment. Nevertheless, Losartan induced an increase in basal RVC, RBF, urine
      flow and UNaV whilst hypoxia induced falls in urine flow and UNaV that were
      proportionately similar to those seen prior to addition of Losartan. 5. These
      results indicate that in the Saffan-anaesthetized rat, AII exerts tonic, renal
      vasoconstrictor and consequent antidiuretic and antinatriuretic influences in
      normoxia, but does not contribute to the hypoxia-induced antidiuresis and
      antinatriuresis. We propose that renin secretion is increased by the hypoxia
      induced fall in RPP rather than by an increase in renal sympathetic activity.
      Thus, the AII generated cannot produce antidiuresis and antinatriuresis by its
      known facilitatory influence on the actions of an increase in sympathetic
      activity on the renal tubules and is insufficient to produce these effects by
      direct actions. Rather, these results support the view that the antidiuresis and
      antinatriuresis of moderate hypoxia is predominantly due to the fall in RPP.

PMID- 8866872
TI  - The behaviour of muscle microcirculation in chronically hypoxic rats: the role of
      adenosine.
AB  - 1. In rats housed in a hypoxic chamber at 12% O2 for 3-5 weeks (CH) and in normal
      rats housed in air (N), we directly observed responses of arterial and venous
      vessels of the spinotrapezius muscle to changes in O2 concentration in the
      inspirate. Both CH and N rats were anaesthetized with Saffan. They had
      haematocrits of 55.0 +/- 0.9% (mean +/- S.E.M.) and 41.9 +/- 0.5%, respectively.
      2. In CH rats breathing 12% O2 and N rats breathing air, arterial and venous
      vessels from comparable anatomical positions in the vascular tree were of similar
      internal diameter. They also showed similar maximum dilator responses to topical
      adenosine (10(-3) M); 14.1 +/- 1.1 and 16.3 +/- 1.7% in all arterioles, 15.5 +/-
      1.2 and 11.5 +/- 0.6% in all venules in CH and N rats, respectively. 3. In CH
      rats, the change from 12% O2 to air for 3 min induced constriction in all
      arterioles and venules (-12.9 +/- 1.0 and -14.3 +/- 1.7%, respectively), whereas
      in N rats, the change from air to 12% O2 for 3 min induced net dilatation (3.9 +/
      1.8% in arterioles and 4.7 +/- 0.8% in venules). Topical application of the
      adenosine receptor antagonist 8-sulphophenyltheophylline (8-SPT, 10(-3) M) had no
      effect on control diameters in CH or N rats, nor on constrictor responses to air
      in CH, but reversed or reduced dilator responses to 12% O2 in N rats (to -2.4 +/-
      1.3% in arterioles and 2.0 +/- 0.9% in venules). 4. In CH rats, the change from
      12 to 8% O2 produced net dilatation as great as that induced in N rats by the
      larger change from air to 8% O2: 8.5 +/- 2.6 and 5.0 +/- 3.7% in arterioles and
      10.3 +/- 1.8 and 6.4 +/- 1.9% in venules, respectively. These responses were
      similarly reduced by 8-SPT to -4.3 +/- 1.9 and -5.2 +/- 2.7% in arterioles and to
      -6.9 +/- 2.0 and -1.5 +/- 2.0% in venules, respectively. 5. These results
      indicate that CH rats were acclimated to 12% O2 such that the resting tone of
      arterial and venous vessels of muscle was comparable to that of N rats breathing
      air. They also suggest that adenosine had little tonic dilator influence in CH
      rats breathing 12% O2 despite its contribution to the dilatation induced in N
      rats by acute exposure to 12% O2. This may reflect the greater haematocrit in CH
      rats which normalized the O2 supply to muscle. However, CH rats were more
      sensitive than N rats to the dilator influence of acute systemic hypoxia and this
      was largely mediated by adenosine.

PMID- 8866873
TI  - Immunomodulation of afferent neurons in guinea-pig isolated airway.
AB  - 1. The trachea, larynx and main bronchi with the right vagus nerve and nodose
      ganglion were isolated from guinea-pigs passively immunized 24 h previously with
      serum containing anti-ovalbumin antibody. 2. The airways were placed in one
      compartment of a Perspex chamber for recording of isometric tension while the
      nodose ganglion and attached vagus nerve were pulled into another compartment.
      Action potentials arriving from single airway afferent nerve endings were
      monitored extracellularly using a glass microelectrode positioned near neuronal
      cell bodies in the ganglion. Mechanosensitivity of the nerve endings was
      quantified using calibrated von Frey filaments immediately before and after
      exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to
      the force exerted by the lowest filament (0.078 mN) and were not further
      investigated. In airways from thirteen immunized guinea-pigs, the mechanical
      sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1)
      was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P < 0.005).
      Mechanical sensitivities of afferent fibres (conduction velocity = 4.3 +/- 0.6 m
      s-1) from non-immunized control guinea-pig airways were unaffected by antigen (n
      = 13). 4. Antigen did not overtly cause action potential generation except in one
      instance when the receptive field was located over the smooth muscle. This ending
      also responded to methacholine suggesting that spatial changes in the receptive
      field, induced by muscle contraction, were responsible for the activation. 5. The
      mediators responsible for these effects are unknown, although histamine,
      prostaglandins, leukotrienes and tachykinins do not appear to be essential. The
      increase in mechanical responsiveness was not associated with the smooth muscle
      contraction since leukotriene C4, histamine and tachykinins, which all caused a
      similar contraction to antigen, did not affect mechanical thresholds. Moreover,
      the antigen-induced increases in excitability persisted beyond the duration of
      the smooth muscle contraction. 6. These results demonstrate that antigen-antibody
      mediated inflammatory processes may enhance the excitability of vagal afferent
      nerve terminals projecting from the airway and thus may contribute to the
      pathophysiology of allergic airway diseases.

PMID- 8866874
TI  - Differential oxygen sensitivity of calcium channels in rabbit smooth muscle cells
      of conduit and resistance pulmonary arteries.
AB  - 1. Calcium currents were recorded from smooth muscle cells dispersed from conduit
      and resistance rabbit pulmonary arteries. We tested the hypothesis that Ca2+
      channel activity was regulated by environmental O2 tension. 2. Conduit (proximal)
      and resistance (distal) myocytes differ in their Ca2+ channel density and
      responses to low PO2. Ca2+ current density in distal myocytes (20.7 +/- 7.4 pA pF
      1, n = 10) is almost twice the value in proximal myocytes (12.6 +/- 5.5 pA pF-1,
      n = 39). In proximal myocytes, the predominant response to reductions in PO2 is
      inhibition of the calcium current (n = 12) at membrane potentials below 0 mV,
      whereas potentiation of current amplitude is observed in distal myocytes (n =
      24). 3. Hypoxia also produces opposite shifts in the conductance-voltage
      relationships along the voltage axis. The average displacements induced by low
      PO2 are +5.05 +/- 2.98 mV (n = 5) in proximal myocytes and -6.06 +/- 2.45 (n =
      10) in distal myocytes. 4. These findings demonstrate longitudinal differences in
      Ca2+ channel density and O2 sensitivity in myocytes along the pulmonary arterial
      tree. These results may help to understand the differential reactivity to hypoxia
      of the pulmonary vasculature: vasodilatation in conduit arteries and
      vasoconstriction in resistance vessels.

PMID- 8866875
TI  - Cardiovascular responses to static exercise in conscious cats: effects of
      intracerebroventricular injection of clonidine.
AB  - 1. Static exercise elicits increases in arterial blood pressure and heart rate
      (HR) in humans and conscious animals. In this study, the effects of
      intracerebroventricular (I.C.V.) administration of clonidine, an alpha 2
      adrenergic agonist, on these cardiovascular responses were investigated using
      conscious cats. Four cats were operantly trained to extend a forelimb and press a
      bar (200-650 g) for 15-60 s. A stainless-steel cannula was inserted into the
      right lateral ventricle for I.C.V. injection of drugs, and a common carotid
      artery was catheterized to measure mean arterial pressure (MAP) and HR. The
      number of exercise trials and changes in MAP, HR and force were pooled for 30 min
      periods. After the cats exercised for 30 min, either artificial cerebrospinal
      fluid (CSF) or clonidine (2 or 5 micrograms) were administered
      intracerebroventricularly. 2. Before clonidine injection, fifty-two exercise
      trials increased MAP and HR by 15 +/- 3 mmHg and 41 +/- 5 beats min-1,
      respectively. Administration of clonidine (2 micrograms) did not alter the
      resting MAP and HR, but attenuated the increases in MAP and HR in response to
      exercise (0-30 min post-clonidine: n = 81; delta MAP, 6 +/- 3 mmHg; delta HR, 20
      +/- 6 beats min-1; 30-60 min post-clonidine: n = 71; delta MAP, 4 +/- 4 mmHg;
      delta HR, 17 +/- 8 beats min-1). Administration of artificial CSF I.C.V. had no
      effect on the cardiovascular responses to static exercise. 3. An increased dose
      of clonidine (5 micrograms) decreased resting MAP and HR by 31 +/- 7 mmHg and 37
      +/- 7 beats min-1, respectively, and markedly blunted the cardiovascular
      responses to exercise (pre-clonidine: n = 52; delta MAP, 17 +/- 3 mmHg; delta HR,
      38 +/- 5 beats min-1; post-clonidine 0-30 min: n = 66; delta MAP, 4 +/- 2 mmHg;
      delta HR, 15 +/- 5 beats min-1; post-clonidine 30-60 min: n = 60; delta MAP, 4 +/
      2 mmHg; delta HR, 14 +/- 6 beats min-1). Pretreatment with the alpha 2
      adrenergic antagonist, yohimbine (8 micrograms, I.C.V.), blocked the attenuating
      effects of I.C.V. administration of clonidine (5 micrograms). 4. These results
      show that stimulation of central alpha 2-adrenoceptors by clonidine attenuates
      the cardiovascular responses to static exercise in conscious cats. In addition,
      this study suggests that alpha 2-adrenoceptors blocked by yohimbine injected
      I.C.V. do not appear to have a tonic influence on HR and blood pressure.

PMID- 8866876
TI  - Plasma catecholamines and hyperglycaemia influence thermoregulation in man during
      prolonged exercise in the heat.
AB  - 1. We manipulated plasma catecholamines (combined adrenaline and noradrenaline
      concentrations) to three levels during prolonged exercise to determine their
      effect on cutaneous and forearm vascular conductance (CVC and FVC), oesophageal
      temperature (T(oes)) and cardiovascular responses. 2. On three occasions, seven
      endurance-trained men cycled at 65% VO2, max in the heat (33.1 +/- 0.7 degrees C)
      for 120-150 min. During the control trial (150 min duration), 0.45% saline was
      intravenously infused (SI) starting at 30 min, at a rate that replaced a third of
      the fluid losses. The infusion start time and rate were identical in all three
      trials. During SI, plasma catecholamine levels increased progressively and were
      18.2 +/- 2.7 pmol ml-1 at 150 min. In another trial (120 min duration),
      adrenaline was infused (AI) at 0.1 microgram kg-1 min-1 and plasma catecholamine
      levels were elevated 6 pmol ml-1 above SI during the 60-120 min period. In a
      third trial (150 min duration), an 18% glucose solution was infused (GI) at a
      rate that maintained plasma glucose levels above 11 mM and plasma catecholamine
      levels were 5.0-5.5 pmol ml-1 lower (P < 0.05) than SI from 120-150 min. 3. Heat
      production and sweat rate were not different during the three trials and neither
      was the decline in stroke volume, cardiac output and mean arterial pressure. 4.
      Soon after beginning AI, CVC decreased 15%, T(oes) increased by 0.4 +/- 0.1
      degree C and heart rate increased by 6 +/- 1 beats min-1; these significant (P <
      0.05) differences from SI were maintained throughout the bout. As a result of GI,
      FVC was 15% higher than SI and T(oes) and heart rate were attenuated by 0.3 +/-
      0.1 degree C and 7 +/- 1 beats min-1 at 150 min compared with SI (P < 0.05). 5.
      In conclusion, large increases in plasma catecholamine levels cause hyperthermia
      during exercise by vasoconstricting the skin. The mechanisms by which
      hyperglycaemia (i.e. 11 mM) attenuates hyperthermia are less clear and may be due
      to others factors besides attenuation of the plasma catecholamine response to
      exercise.

PMID- 8866877
TI  - Potentiation and depression of the M wave in human biceps brachii.
AB  - 1. The effects of repeated excitation on the compound action potential, or M
      wave, of mammalian muscle fibres have been investigated in the human biceps
      brachii. 2. During continuous indirect stimulation at 10 and 20 Hz the mean
      voltage-time area of the M wave doubled within the first minute, while the mean
      peak-to-peak amplitude increased by approximately half. The enlargement of the M
      wave was sustained during stimulation at 10 Hz but not at 20 Hz. Stimulation at 3
      Hz caused a small increase which was significant for M wave amplitude only. 3.
      When the 20 Hz stimulation was performed under ischaemic conditions, the M wave
      first enlarged and then gradually declined. After 20 Hz stimulation was
      discontinued, the M wave increased in size; in the ischaemic experiments the
      release of the cuff produced a further, rapid augmentation. In both the ischaemic
      and non-ischaemic experiments, the amplitudes and areas of the M waves during the
      recovery period became significantly larger than the resting values (range, 15
      60% at the endplate zone). 4. The mean muscle fibre impulse conduction velocity
      decreased to less than half the resting value during 20 Hz stimulation, with or
      without ischaemia, and then increased above the resting value during recovery. 5.
      On the basis of previous experiments in animals, the augmentation of the M wave
      was attributed to enhanced electrogenic Na(+)-K+ pumping, and the biceps brachii
      appeared to be an excellent preparation for studying the time course of this
      enhancement.

PMID- 8866878
TI  - Selective facilitation of responses to cortical stimulation of proximal and
      distal arm muscles by precision tasks in man.
AB  - 1. The responses of the first dorsal interosseus (1DI), opponens pollicis (OP),
      extensor digitorum communis (EDC), brachioradialis (BR), biceps brachii (BB) and
      anterior deltoid (AD) muscles to magnetic stimulation of the motor cortex were
      recorded during different motor tasks. 2. Two precision and two power isometric
      tasks were investigated. The precision tasks were a pincer grip ('grip') and a
      thrust against a target with the wrist ('push'). In the former, the prime movers
      were the intrinsic hand muscles, while the proximal muscles played a postural
      role. In the latter, the prime movers were the proximal muscles. In both tasks,
      force was controlled through visual feedback. The power tasks required
      encirclement of a cylinder with the fingers ('grasp'), or sustaining a weight
      suspended at wrist level ('load'). 3. Magnetic stimulation was applied in eight
      subjects by a coil placed over the vertex at 1.1-1.2 times the motor threshold
      for the most excitable muscles. This produced in the prime mover muscles larger
      motor-evoked responses (MEPs) during grip or push tasks than grasp or load tasks,
      in spite of similar background EMG levels. During grip tasks, only one of the two
      prime movers showed task-dependent changes. In the postural muscle AD there was
      no significant difference between MEPs during grip and grasp tasks; however, BB
      responses were larger during grasp than grip tasks. 4. MEPs simultaneously
      recorded in the prime movers were plotted against each other. The slope of the
      regression line for AD versus BB was larger in push than load tasks, whilst the
      changes in MEPs of 1DI and OP were independent during both grip and grasp tasks.
      5. In three subjects, MEPs were also elicited by electrical stimulation during
      grip and grasp tasks. MEP changes tended to parallel those obtained for magnetic
      stimulation, but the increase in size of the electrically evoked MEPs during the
      precision task was smaller. 6. In all subjects the median and ulnar nerves were
      stimulated during grip and grasp tasks, and an H reflex was evoked in the hand
      muscles of five subjects. In no case did the two tasks produce reflexes of
      different amplitude. 7. The motor response of both proximal and distal muscles
      can be task dependent, in spite of the differences in their principal functional
      role and cortical representation. The modulation is related to the degree of
      control requested by the task, and is likely to reflect selective changes in the
      excitability of corticospinal neurones.

PMID- 8866879
TI  - Acetylcholine activates two currents in guinea-pig outer hair cells.
AB  - 1. Whole-cell voltage clamp recordings were made from outer hair cells (OHCs)
      isolated from the basal and middle regions of the cochlea. The current produced
      when acetylcholine (ACh) was applied to the basal pole was investigated. 2.
      Acetylcholine (50-70 microM) activated an early inward current followed by a late
      outward current in most cells at -70 mV. The activation of the early current was
      very rapid, with no delay. 3. The late outward current was a K+ current and was
      the major component of the total ACh-sensitive current at negative voltages. 4.
      The ACh-sensitive current was voltage dependent. From tail current measurements,
      the current was maximal at -55 mV and declined steeply at more positive
      potentials. On average, 50% of the current was active at -22 mV and 10% was
      active at 0 mV. This decline was caused by a reduction in the K+ current with
      depolarization. Between +20 and +40 mV, the major component of the ACh-sensitive
      current was the early current. 5. The steady-state I-V curve for the ACh
      sensitive current was N-shaped, with a peak at -36 mV. The instantaneous I-V
      curve for the ACh-sensitive current taken from measurements just after a voltage
      step was outwardly rectifying and did not show this peak. This difference
      occurred because the voltage dependence was time dependent. 6. The reversal
      potential for the early current was estimated to be close to+13 mV, in accordance
      with it being a non-specification current. 7. The K+ current was abolished by the
      removal of external Ca2+. The effect occurred with no measurable delay. When
      external Ca2+ was lowered to 0.4 mM, the peak of the steady-state I-V curve for
      the ACh-sensitive current shifted by up to -20 mV and its amplitude was reduced.
      These results suggested that the K+ current was dependent on Ca2+ influx. 8. The
      inward current usually remained when the K+ current was abolished or greatly
      reduced by removing external Ca2+ or by dialysing the cells with BAPTA (5-10 mM).
      9. Both early and late currents were reversibly blocked by alpha-bungarotoxin
      (0.2 microM) and curare (1 microM). 10. A simple scheme is proposed to account
      for the response. ACh, binding to a nicotinic receptor, directly gates the early
      cation current. Part of this current is carried by Ca2+, which once inside the
      cell leads to the activation of a Ca(2+)-dependent K+ current.

PMID- 8866880
TI  - Effects of sympathetic inhibition on blood pressure and renal responses to
      central hypervolaemia in normal humans.
AB  - The purpose of this study was to evaluate the effects of short-term sympathetic
      inhibition with clonidine on blood pressure and renal responses to central
      hypervolaemia induced by thermoneutral head-out water immersion. Eleven healthy
      subjects were randomly studied on two occasions, during a 1 h pre-immersion
      period, 2 h of water immersion and a 1 h post-immersion period, after either
      placebo or clonidine treatment. Clonidine caused a significant suppression of
      plasma adrenaline, plasma noradrenaline, urinary noradrenaline excretion and mean
      arterial blood pressure. Blood pressure remained constant during water immersion
      after both placebo and clonidine, compared with the respective pre-immersion
      control values. The suppression pattern of plasma catecholamines and urinary
      noradrenaline in response to water immersion during placebo was similar after
      clonidine treatment. Renal volume excretion was not affected by clonidine. In
      contrast, clonidine caused a significant attenuation of the immersion-induced
      stimulation of natriuresis (maximum -33 +/- 12%, P < 0.01, compared with
      placebo). These data indicate that the renal capacity to excrete sodium is
      impaired during moderate blood pressure reduction by short-term sympathetic
      inhibition with clonidine, whereas the regulation of arterial blood pressure in
      response to central hypervolaemia is maintained.

PMID- 8866881
TI  - Local vascular responses to elevation of an organ above the heart.
AB  - Elevation of an organ above the heart reduces the arterial and venous hydrostatic
      pressures in proportion to the height of elevation. Intact autoregulation
      protects organs, such as the brain and skeletal muscle, from significant
      alterations in blood flow and hydrostatic capillary pressure due to the decrease
      in arterial inflow pressure during such a manoeuvre. However, the consequences of
      the decreased hydrostatic pressure on the venous side are far from clarified. The
      present study analyses the local haemodynamic effects of the decrease in arterial
      and venous hydrostatic pressures that occur during vertical elevation of an organ
      above the heart at atmospheric and raised tissue pressures (0, 10 and 30 mmHg). A
      sympathectomized cat skeletal muscle enclosed in a plethysmograph and perfused
      from the animal was used as the experimental model. The results show that
      elevation of the muscle above the heart at atmospheric tissue pressure created a
      variable vascular resistance starting at the venous outlet of the organ, and
      related to the difference between tissue pressure and venous outflow pressure.
      This resistance completely protects the organ from the hydrostatic pressure
      alterations on the venous side. The results also show that arterial pressure
      variations will exert the same haemodynamic influences on the organ as tissue
      pressure variations, except for the formation of the venous outflow resistance at
      raised tissue pressure. The application of these results to normal and injured
      organs, e.g. normal and injured skeletal muscle and brain, with various tissue
      pressures, is discussed.

PMID- 8866882
TI  - Acute effects of C-peptide on the microvasculature of isolated perfused skeletal
      muscles and kidneys in rat.
AB  - The C-peptide has recently been suggested to have beneficial effects in several
      organs and improve glycaemic control in human type I diabetes, while there were
      no such effects in healthy controls. The exact mechanisms behind these effects
      are, however, not clear. In an attempt to study the actions of C-peptide on the
      microvasculature in normal rats during more controlled conditions, isolated rat
      hindquarters and kidneys were perfused with albumin solutions in order to obtain
      low basal concentrations of C-peptide. In rat hindquarters, infusion of C-peptide
      significantly increased the capillary filtration coefficients (CFC) from 0.035 +/
      0.002 to 0.044 +/- 0.002 mL min-1 100 g-1 mmHg-1 (P < 0.001, n = 9) and the
      permeability surface area product (PS) for vitamin B12 from 3.48 +/- 0.29 to 4.02
      +/- 0.37 mL min-1 100 g-1 (P < 0.01, n = 6). Addition of C-peptide to the
      perfusate during infusion of sodium nitroprusside did not induce any additional
      alteration of CFC or PS. The vascular resistance was slightly decreased from 2.74
      +/- 0.17 to 2.64 +/- 0.17 mmHg min 100 g mL-1 (P < 0.01, n = 9). These effects of
      C-peptide are compatible with increases in capillary surface area without
      alteration of the permeability per se. In isolated rat kidneys perfused at low
      temperature (8 degrees C) prepared to inhibit all metabolic processes. C-peptide
      induced no changes in glomerular filtration rate, total vascular resistance or
      fractional albumin clearance. Therefore, C-peptide causes active vasodilation of
      the normothermic microvasculature and hence recruitment of capillaries. These
      findings support the previous observations in man that C-peptide indeed has
      biological effects.

PMID- 8866883
TI  - Effect of nitric oxide and renal nerves on renomedullary haemodynamics in SHR and
      Wistar rats, studied with laser Doppler technique.
AB  - The threshold for activation of the humoral renal antihypertensive system,
      presumably residing in the renomedullary interstitial cells (RIC), is
      substantially reset upwards in the spontaneously hypertensive rat (SHR).
      Depressor reactions, normally elicited by an increased renal perfusion pressure,
      can be inhibited either by high frequency renal nerve stimulation or blockade of
      nitric oxide synthesis, i.e. manoeuvres decreasing renal blood flow at this high
      perfusion pressure. The present study was designed to explore the effects on
      regional renal haemodynamics of blocking NO synthesis with N-omega-nitro-L
      arginine (L-NNA) in chloralose anaesthetized SHR and Wistar rats. Mean arterial
      blood pressure (MAP), heart rate (HR), renal blood flow (RBF), cortical blood
      perfusion (CBP) and papillary blood perfusion (PBP) were measured in renally
      innervated and denervated SHR (Si n = 8, Sd n = 8) and in Wistar rats (Wi n = 10,
      Wd n = 10). An innervated non-treated Wistar group served as control (Ci n = 12).
      The laser Doppler technique was used to record CBP and PBP. MAP increased in all
      groups receiving L-NNA while HR, RBF and CBP simultaneously decreased. The
      relative decreases in RBF were more marked into the two SHR groups than in the
      corresponding Wistar groups. After L-NNA PBP also decreased in all four groups
      despite the increased MAP and more so in the Si group; Wi -19 +/- 8 (P < 0.05),
      Wd -17 +/- 6 (P = 0.07), Si -50 +/- 9 (P < 0.01) and Sd -25 +/- 9% (P < 0.05). We
      conclude that NO is important for maintaining PBP especially in SHR. The more
      marked decrease in PBP in the innervated SHR suggests a NO/renal nerve
      interaction in the control of renomedullary blood flow in SHR. This finding may
      be of importance for the regulation of the humoral renal depressor mechanism.

PMID- 8866884
TI  - Role of L-arginine in preventing myocardial and endothelial injury following
      ischaemia/reperfusion in the rat isolated heart.
AB  - The protective effect of L-arginine on ischaemia/reperfusion-induced myocardial
      injury was investigated in the rat isolated Langendorff perfused heart. Six
      groups of hearts subjected to 30 min global ischaemia and 30 min reperfusion
      received either vehicle, D-arginine, L-arginine, the nitric oxide (NO)-donor S
      Nitroso-N-Acetyl-D, L-Penicillamine (SNAP), the inhibitor of NO formation NG
      nitro-L-arginine (L-NNA), or L-arginine plus L-NNA. The recoveries of left
      ventricular double product and coronary flow at the end of reperfusion were
      significantly higher in the L-arginine group (85 +/- 5 and 75 +/- 6%,
      respectively) than in the vehicle group (37 +/- 6 and 34 +/- 5%, respectively, P
      < 0.05). During both the ischaemic and reperfusion periods, left ventricular end
      diastolic pressure was lower in the L-arginine group than in the vehicle group.
      Creatine kinase outflow and the area of no-reflow were smaller in the L-arginine
      treated hearts (P < 0.01). There were no differences between vehicle and D
      arginine treated groups. L-NNA did not affect recovery per se but abolished the
      protective actions of L-arginine. SNAP produced the same protective effects as L
      arginine. Acetylcholine-induced endothelium-dependent vasodilation was reduced
      after ischaemia and reperfusion in the vehicle group but not in the L-arginine
      group. It is concluded that L-arginine reduces ischaemia/reperfusion-induced
      myocardial and endothelial injury. The results suggest that the beneficial
      effects of L-arginine are related to preserved synthesis and release of NO.

PMID- 8866885
TI  - Effect of changes in transmural pressure on contraction frequency of the isolated
      right atrium of the rabbit.
AB  - Experiments were made on preparations of the rabbit right atrium maintained at 37
      degrees C in oxygenated Krebs-Henseleit solution. Baseline diastolic transmural
      pressure was held at 2 mmHg. A step increase in diastolic pressure was
      accompanied by an immediate and rapid increase in atrial rate (fast response),
      followed by a slower increase (t1/2 approximately 0.5 min) (slow response). The
      slow response to pressure steps was graded, approaching a maximum increase after
      a 12 mmHg step (44 +/- 4 min-1 from a baseline of 196 +/- 5 min-1; mean +/- SEM;
      n = 7; P < 0.01). In preparations where baseline atrial rate had been reduced 50%
      by application of carbamylcholine, the slow response to an increase in pressure
      was augmented (n = 7; P < 0.01); an increase of 55 +/- 9 min-1 for a 12 mmHg step
      in atrial pressure. In preparations where baseline rate had been increased 63% by
      the application of isoprenaline, the slow response was attenuated (n = 5, P <
      0.01), an increase of 22 +/- 7 min-1 for a 12 mmHg step. During sinusoidal
      pressure forcing (0.002-1.0 Hz), rate responses of control and carbamylcholine
      treated preparations had a high gain at frequencies < or = 0.02 Hz.
      Carbamylcholine-treated preparations also showed a high gain at frequencies > or
      = 0.2 Hz. There appear to be two distinct intrinsic responses to changes in right
      atrial pressure; a rapid response which is augmented by cholinergic stimulation,
      and a slower response which is augmented by cholinergic stimulation and reduced
      by beta-adrenergic stimulation.

PMID- 8866886
TI  - Ischaemia-reperfusion induced alterations of mitochondrial function in
      hypertrophied rat heart.
AB  - The impact of in vivo ischaemia and ischaemia-reperfusion (I-R) on mitochondrial
      respiratory function was investigated in hypertrophied (HP) hearts with aortic
      constriction compared with control hearts using an open-chest rat surgical model.
      Moreover, mitochondrial susceptibility to superoxide radicals (O2-.) in vitro was
      examined in HP and control hearts with or without I-R. With the site I substrates
      pyruvate-malate, mitochondrial state 4 (basal) respiration and the respiratory
      control index (RCI) were not affected by either ischaemia alone or I-R in both HP
      and control hearts. State 3 (ADP-stimulated) respiration was increased with I-R
      in control hearts, but showed a reduction after I-R in the HP hearts. Exposure of
      mitochondria to O2-. (20 nM hypoxanthine in the presence of 0.13 unit mL-1
      xanthine oxidase) significantly increased state 4 respiration, whereas state 3
      respiration and RCI were decreased in all treatment groups. I-R hearts in both HP
      and control showed greater increases in state 4 respiration with O2-. than either
      sham or ischaemic hearts. HP hearts exhibited a significantly lesser extent of
      inhibition in state 3 respiration and RCI by O2-. compared with control hearts.
      These changes in mitochondrial respiratory properties were not observed with the
      site II substrate succinate. Myocardial reduced vs. oxidized glutathione ratio
      was significantly decreased after I-R in both control and HP hearts.
      Malondialdehyde content showed an increase with I-R, but the increase was
      significant only in control hearts. These data indicate that short-term in vivo I
      R does not impair heart mitochondrial respiratory function, but renders the
      organelles more vulnerable to imposed oxidative stress. Mitochondria from the HP
      hearts are more resistant to free radical damage under normal and ischaemic
      conditions; however, this advantage is severely compromised after reperfusion.

PMID- 8866887
TI  - Impaired glomerular permselectivity for albumin in chemically medullectomized WKY
      rats.
AB  - Chemical renal medullectomy with 2-bromo-ethylamine hydrobromide (BEA) has been
      used to study the importance of the renal medulla in blood pressure regulation.
      However, conclusive evidence as to whether BEA treatment affects the glomerular
      barrier is lacking. In the present study, the effects of BEA upon glomerular
      permselectivity for albumin were studied using isolated kidneys (IPK) perfused at
      a low temperature (8 degrees C) to inhibit tubular reabsorption of proteins.
      Sixteen WKY rats (WB) received an i.v. injection of BEA (150 mg kg-1) while 10
      rats served as controls (WC). Volume balance, urinary osmolality and creatinine
      clearance (GFR) were measured in metabolic cages. Acute paired experiments (n =
      9) were performed 5-7 weeks after BEA. The rats were anaesthetized and the total
      in vivo albumin excretion was recorded. The kidneys were then isolated and
      perfused for measurements of inulin clearance (GFR) and fractional albumin
      clearance without tubular reabsorption of protein. The nine BEA treated rats
      showed polyuria and hypoosmotic urine. In vivo GFR was lower in the BEA treated
      groups when measured with creatinine clearance (459 +/- 22 vs. 213 +/- 41 microL
      min-1 100 g-1 body wt, P < 0.001), while GFR was not significantly changed in the
      IPK (WC = 135 +/- 27, WB = 92 +/- 14 microL min-1 100 g-1 body wt, n.s.) when
      perfused at identical pressures. The fractional albumin clearance was increased
      three times in the BEA group (WB = 9.6 +/- 3.4/1000, P < 0.05). Moreover, albumin
      excretion in vivo was similar in the two groups despite low GFR in the BEA group.
      We conclude that BEA treatment affects glomerular permselectivity for albumin.

PMID- 8866888
TI  - The relationship between interstitial fluid pressure and volume in rat trachea.
AB  - A change of interstitial fluid volume (IFV) will normally change the interstitial
      fluid pressure (Pif) so as to counteract further fluid movement across the
      capillaries and changes in IFV. Contrary to this, several acute inflammatory
      reactions in the trachea are associated with increased negativity of Pif, which
      will 'actively' generate oedema. To outline further the role of Pif in
      interstitial fluid balance in the trachea, interstitial compliance (delta
      IFV/delta Pif) was measured in pentobarbital anaesthetized rats. IFV was measured
      as the plasma equivalent extravascular distribution space of [51Cr]EDTA. Pif was
      measured in the same animal with sharpened glass pipettes (diameter 3-6 microns)
      connected to a servocontrolled counterpressure system. In dehydration (30 mL
      saline i.v., n = 10) interstitial compliance was 0.083 mL g dry wt-1 mmHg-1.
      Since control IFV was 1.046 mL g dry wt-1 (n = 10) the interstitial compliance is
      8% of IFV per mmHg. In overhydration (30 mL NaCl, n = 10) and dextran anaphylaxis
      (1 mL dextran 70, n = 10) compliance remained the same for the first 15% increase
      in IFV and then increased several-fold since Pif did not increase more than 2
      mmHg above control level. The increased negativity of Pif by -10 mmHg associated
      with acute inflammation will require a reduction of IFV by 80% when interstitial
      compliance is 8% per mmHg. A more likely explanation is therefore that structural
      rearrangements are responsible for the events leading to increased negativity of
      Pif in acute inflammation.

PMID- 8866889
TI  - Electrophoretic analysis of rat parotid salivary protein composition:
      investigation of the parasympathetic atropine-resistant secretion.
AB  - Rats pretreated with atropine and adrenoceptor antagonists show secretion of
      saliva upon electrical stimulation of the parasympathetic nerve of the parotid
      gland. The protein composition of this secretion has been analysed by sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and compared with
      the protein profiles obtained with secretions evoked by parasympathetic
      stimulation (in the absence of atropine) or infusion of bethanechol with or
      without vasoactive intestinal peptide (VIP, a probable transmitter conveying
      parasympathetic secretory impulses). The SDS-PAGE patterns were highly
      reproducible for an individual rat although minor differences were detected
      between different rats. The method requires only microlitre volumes of
      unconcentrated rat saliva and thus is ideal for monitoring sequential aliquots
      collected from the same rat. The SDS-PAGE patterns indicated (i) little change in
      the protein profile during prolonged stimulation, (ii) a similar profile with
      parasympathetic stimulation or infusion of bethanechol, and (iii) a quantitative,
      rather than qualitative, response to administration of atropine (during
      parasympathetic stimulation) or VIP (during bethanechol infusion). Thus, the
      salivary protein composition associated with non-adrenergic, non-cholinergic
      (NANC) secretion appears similar to that evoked in response to parasympathetic
      nerve stimulation in the absence of muscarinic receptor blockade.

PMID- 8866890
TI  - A comparison of the effects of two antispastic drugs, tizanidine and baclofen, on
      synaptic transmission from muscle spindle afferents to spinal interneurones in
      cats.
AB  - The alpha 2-adrenergic agonist tizanidine was reported to be more efficient than
      baclofen in reducing muscle tone in some spastic patients. The aim of this study
      was to investigate if this might be due to more specific depressive actions of
      tizanidine on transmission from muscle afferents which contribute to muscle tone.
      This was done by comparing the effects of tizanidine and baclofen on amplitudes
      of monosynaptic spinal focal field potentials produced by stimulation of muscle
      nerves in the cat. Such field potentials were recorded in the intermediate zone
      of the fourth lumbar segment, where they display two distinct components, an
      early one from group I afferents and a later one from group II afferents. Both
      reflect EPSPs produced in interneurones in disynaptic pathways to motoneurones.
      Tizanidine strongly depressed potentials caused by group II afferents, while it
      had no effect or slightly facilitated potentials produced by group I afferents.
      In contrast, baclofen had inconsistent effects on the group II potentials; in
      some cases it caused a depression and in others it caused only an increase in the
      latency and time to peak, at doses that strongly and consistently depressed the
      group I potentials. These effects have been found after both local and systemic
      applications. The antispastic actions of tizanidine may therefore only be related
      to the depression of transmission from group II muscle afferents, while
      antispastic actions of baclofen may be secondary to the depression of any sensory
      fibres. Since tizanidine is as effective in depressing spasticity as baclofen, it
      is suggested that the enhancement in synaptic transmission from group II muscle
      afferents may play an important role in the development of exaggerated stretch
      reflexes in spastic patients.

PMID- 8866891
TI  - Evidence for genomic changes in transgenic rice (Oryza sativa L.) recovered from
      protoplasts.
AB  - The occurrence of genomic modifications in transgenic rice plants recovered from
      protoplasts and their transmission to the self-pollination progeny has been
      verified with the random amplified polymorphic DNA (RAPD) approach. The plant was
      the Indica-type rice (Oryza sativa L.) cultivar Chinsurah Boro II. The analysed
      material was: (1) microspore-derived embryogenic rice cells grown in suspension
      culture, (2) transgenic plants recovered from protoplasts produced from the
      cultured cells and (3) the self-pollination progeny (two successive generations)
      of the transgenic plants. DNA purified from samples of these materials was PCR
      amplified with different random oligonucleotide primers and the amplification
      products were analysed by agarose gel electrophoresis. Band polymorphism was
      scored and used in band-sharing analyses to produce a similarity matrix.
      Relationships among the analysed genomes were expressed in a dendrogram. The
      extensive DNA changes evidenced in cultured cells demonstrate the occurrence of
      somaclonal variation in the material used to produce protoplasts for gene
      transfer. Quantitatively reduced DNA changes were also found in the resulting
      transgenic plants and in their self-pollination progenies. While confirming the
      stability of the foreign gene in transgenic plants, this work gives molecular
      evidence for the occurrence of stable genomic changes in transgenic plants and
      points to in vitro cell culture as the causative agent. RAPDs are shown to be a
      convenient tool to detect and estimate the phenomenon at the molecular level. The
      methodology is also proposed as a fast tool to select those transgenic
      individuals that retain the most balanced genomic structure and to control the
      result of back-crosses planned to restore the original genome.

PMID- 8866892
TI  - A system for tissue-specific copper-controllable gene expression in transgenic
      plants: nodule-specific antisense of aspartate aminotransferase-P2.
AB  - A vector system, based on copper controllable gene expression, has been developed
      to give control over place as well as time of expression of an introduced gene.
      This system consists of two elements: (1) the yeast ace1 gene encoding a metallo
      regulatory transcription factor, ACE1, under control of either an organ-specific
      or a constitutive promoter; and (2) a gene of interest under control of a
      chimaeric promoter consisting of the 46 bp TATA fragment of the CaMV 35S RNA
      promoter linked to four repeats of the ACE1 binding site. The functioning of the
      system in an organ-specific manner was tested in nodulated Lotus corniculatus
      plants which consisted of non-transformed shoots plus transformed hairy root
      tissue 'wild-type tops/transgenic roots'. After addition of copper ions to the
      plant nutrient solution, beta-glucuronidase (GUS) expression was visualized
      either specifically in nodules or in both roots and nodules when the ace1 gene
      was placed under control of the nod45 promoter or the CaMV 35S RNA promoter,
      respectively. The nodule-specific system was used to express antisense constructs
      of aspartate aminotransferase-P2 in transgenic Lotus corniculatus plants. When
      expression was induced by the addition of copper ions to the plant nutrient
      solution aspartate aminotransferase-P2 activity declined dramatically, and a
      decrease of up to 90% was observed in nodule asparagine concentration.

PMID- 8866893
TI  - Modification of fatty acid composition by over- and antisense-expression of a
      microsomal omega-3 fatty acid desaturase gene in transgenic tobacco.
AB  - omega-3 fatty acid desaturases, which catalyse the conversion of linoleic acid
      (18:2) to linolenic acid (18:3) in lipids, are located in the microsomes and
      plastid membranes. Transgenic tobacco plants were produced that express the
      transcripts of a tobacco microsomal omega-3 fatty acid desaturase gene (NtFad3)
      in antisense and sense orientations under the control of the cauliflower mosaic
      virus 35S promoter. The antisense construct has the 0.5-kb fragment of the NtFad3
      cDNA containing a 3'-flanking region and a part of the coding region in antisense
      orientation. The antisense-transformant lines showed decreases of the steady
      state NtFad3 mRNA level to 30% of the control plants. In these lines, the 18:3
      content decreased to about 80% in root tissues and to about 70-80% in leaf
      tissues when compared with the control plants. The sense construct has the 1.4-kb
      full-length cDNA of NtFad3. In one of the sense-transformant lines, the NtFad3
      mRNA level increased 8 times when compared with that of the control plants. In
      this line, the 18:3 content increased by about 1.5-fold in root tissues and by
      about 1.1-fold in leaf tissues. These results indicate that the up- and down
      regulation of the transcript level in the microsomal omega-3 fatty acid
      desaturase gene is useful to modify the 18:3 content in the vegetative tissues of
      higher plants.

PMID- 8866894
TI  - The cysteine-rich and C-terminal domains of dystrophin are not required for
      normal costameric localization in the mouse.
AB  - Dystrophin has a modular structure and is believed to be critical for muscle cell
      cytoarchitecture by linking the cytoskeleton to the extracellular matrix. The N
      terminus binds to actin and two domains at the C-terminus, the cysteine-rich and
      C-terminal domains, are associated with the sarcolemma indirectly via the
      dystroglycan complex. We have generated a mutation in mouse embryonic stem (ES)
      cells which serves to delete the cysteine-rich and C-terminal domains to address
      directly their role. We show that these two domains are not necessary for normal
      costameric organization at the sarcolemma in myotubes derived from the mutant
      cell line. Furthermore sarcolemmal localization is also apparent in mouse
      chimaeric muscle in vivo.

PMID- 8866896
TI  - Exploiting transgenic technology: a commercial development conundrum.

PMID- 8866895
TI  - A human SP-C promoter fragment targets alpha 1-proteinase inhibitor gene
      expression to lung alveolar type II cells in transgenic mice.
AB  - A 1.277 kb promoter fragment of the gene encoding one of the lung surfactant
      proteins, SP-C, was cloned from a human genomic library and characterized using
      the human alpha 1-proteinase inhibitor (alpha 1PI) gene as reporter. Messenger
      RNA for human alpha 1PI isolated from a single transgenic mouse line was detected
      solely in lung tissue. Using immunogold electron microscopy, accumulation of
      human alpha 1PI was shown unambiguously to occur only in type II pulmonary cells
      and, in discrete amounts, in the alveolar lining fluid. The protein was secreted
      and glycosylated showing a molecular weight close to that of plasma-derived human
      alpha 1PI.

PMID- 8866897
TI  - Economics and the treatment of hypertension.

PMID- 8866898
TI  - Renal haemodynamic and protective effects of calcium antagonists in hypertension.
AB  - In recent years, the ability of the various antihypertensive drugs to provide
      renal protection has been the subject of increased attention. Whether calcium
      antagonists prevent or reduce the rate of progression of renal damage is still a
      matter of controversy. This paper reviews the findings of recent animal and human
      studies on the haemodynamic and renal protective effects of calcium antagonists.
      These agents preferentially vasodilate afferent arterioles, leading to an
      increase in renal blood flow and glomerular filtration rate. These effects are
      more pronounced in hypertensive patients than in normotensive subjects and
      persist even when renal function is impaired. In animal models of chronic renal
      failure, calcium antagonists can reduce glomerulosclerosis. However, the
      mechanisms involved in their renal protective effect appear to be different from
      those of angiotensin converting enzyme (ACE) inhibitors as they do not reduce
      intraglomerular pressure. Renal failure caused by vasoconstriction related to
      radiocontrast agents or cyclosporine can be partly prevented by the
      administration of a calcium antagonist. Furthermore, in patients with renal
      artery stenosis, calcium antagonists reduce blood pressure with less renal blood
      flow impairment than ACE inhibitors. Preliminary clinical studies suggest that
      verapamil or diltiazem may reduce proteinuria in hypertensive diabetic patients.
      Whether these compounds can also retard the progression of renal failure in these
      patients remains to be established with larger trials.

PMID- 8866899
TI  - Ambulatory blood pressure normality: results from the PAMELA study.
AB  - OBJECTIVE: To determine ambulatory and home blood pressure means and
      distributions in relation to clinic blood pressure in a general population.
      METHODS: We obtained a random sample of 2400 subjects stratified by sex and 10
      year age groups to be representative of residents aged 25-64 years of the city of
      Monza. Participation rate was 69% (1651 subjects). Blood pressure measurements
      consisted of clinic blood pressure (average of three measurements,
      sphygmomanometry), home blood pressure (average of morning and evening
      measurements, semiautomatic device) and ambulatory blood pressure (automatic
      readings at 20 min intervals, Spacelabs 90207). Clinic blood pressure was
      obtained both before and after home and ambulatory blood pressures. Data analysis
      did not include 213 subjects receiving antihypertensive drug treatment and was
      therefore limited to 1438 participants. RESULTS: In the 1438 subjects, clinic,
      home and ambulatory blood pressure showed a normal-like distribution, with a
      taller peak and a narrower base for ambulatory than for home and clinic values.
      Clinic, home and ambulatory blood pressures were significantly related to each
      other (P always < 0.001). The means of the two clinic blood pressures obtained on
      consecutive days were superimposable (127.4 +/- 17.0/82.3 +/- 9.8 and 128.2 +/-
      16.5/81.9 +/- 9.9 mmHg) and both were markedly higher than home and 24 h average
      blood pressures (8.2 mmHg), which were similar to one another. The differences
      between clinic and home or 24 h average blood pressure were similar in both sexes
      but increased with increasing age and clinic blood pressure values. The influence
      of clinic blood pressure values on the clinic-ambulatory or clinic-home blood
      pressure differences was more important than age. Although higher than the 24 h
      average value, daytime average blood pressure was also lower than clinic blood
      pressure. Night-time blood pressure was markedly lower than the daytime value in
      both sexes and at all ages. CONCLUSION: Data from a large and unbiased sample of
      a general population show that home and 24 h or daytime average blood pressures
      are much lower than clinic blood pressure. The relatively close correlation
      between blood pressure values measured with the different methods used has
      allowed calculation of home and ambulatory blood pressure values corresponding to
      the accepted upper limit of normality of clinic blood pressure (140/90 mmHg). The
      upper limit of normality for the population was for both home and ambulatory
      blood pressures in the range 120-130 and 75-81 mmHg for systolic and diastolic
      values, respectively, with slight differences depending on sex and age. Taking
      140/90 mmHg as the upper normal limit of the population is therefore an error
      that leads to individuals whose home or ambulatory blood pressures are high being
      considered as normotensive.

PMID- 8866900
TI  - Captopril and stress-induced hypertension in the borderline hypertensive rat.
AB  - OBJECTIVE: Daily exposure to air-jet stress (AJS) causes sustained elevations of
      blood pressure in borderline hypertensive rats (BHR). It is known that the renin
      angiotensin system is activated during episodes of behavioral stress, and the
      purpose of this study was to assess the involvement of renin-angiotensin system
      in the development of stress-induced hypertension in the BHR. DESIGN: Four groups
      of 8- and 9-week-old rats were studied: they received, respectively, oral
      captopril and AJS; oral captopril without AJS; AJS without captopril; and neither
      AJS nor captopril. METHODS: After 10 days of AJS and captopril conditions,
      femoral and jugular catheters were implanted for the measurement of mean arterial
      pressure and pressor responses to norepinephrine and tyramine. Blood samples were
      collected for the measurement of norepinephrine and plasma renin activity.
      RESULTS: Ten days of AJS caused a significant elevation of blood pressure in BHR
      exposed to AJS without receiving captopril but not in those animals given
      captopril concurrently with AJS. Circulating norepinephrine and blood pressure
      responses to exogenous norepinephrine and tyramine were similar across the four
      groups. Plasma renin activity was highest in BHR given captopril, and was
      significantly elevated during an acute episode of AJS. CONCLUSIONS: The renin
      angiotensin system may be important in the development of stress-induced
      hypertension in the BHR.

PMID- 8866901
TI  - Osmotically induced natriuresis and blood pressure response involves angiotensin
      AT1 receptors in the subfornical organ.
AB  - OBJECTIVE: In the present study we tested the hypothesis of whether the centrally
      induced natriuresis and blood pressure increase after intracerebroventricular
      injection of hypertonic saline involves the subfornical organ, as suggested by
      the occurrence of osmosensitive cells as well as a high concentration of
      angiotensin II receptors in this brain area. METHODS: All experiments were
      performed in conscious Wistar rats. A chronic cannula was inserted into the
      lateral brain ventricle for intracerebroventricular injection and a chronic
      indwelling intracranial guide cannula for microinjection was placed in the
      subfornical organ. In addition, the rats were provided with ureter catheters for
      urine collection. RESULTS: Intracerebroventricular injections of hypertonic
      saline (0.3 mol/l; n = 7) increased renal sodium excretion from 180.0 +/- 30.0 to
      279.0 +/- 34.0 mol/l/60 min (P < 0.001) accompanied by an increase in mean
      arterial pressure of 8.3 +/- 1.2 mmHg (P < 0.01). No change in urinary volume was
      observed. After injection of the specific AT1 receptor antagonist, losartan, into
      the subfornical organ (5 micrograms/200 nl; n = 8) the natriuresis and blood
      pressure response to intracerebroventricular hypertonic saline was completely
      abolished. Control injections of losartan into areas adjacent to the subfornical
      organ had no effect on the responses to hypertonic saline. CONCLUSION: Our
      results suggest that the centrally induced natriuresis and blood pressure
      responses to hypertonic saline are mediated by an angiotensinergic mechanism
      involving the subfornical organ.

PMID- 8866902
TI  - Blockade of the renin-angiotensin system in heart failure in conscious dogs.
AB  - OBJECTIVE: To study the different cardiac and renal hemodynamic effects of an
      angiotensin converting enzyme inhibitor and an angiotensin II receptor antagonist
      in experimental heart failure in conscious dogs. DESIGN AND METHODS: We compared
      the effects of the angiotensin converting enzyme inhibitor, captopril, with those
      of the angiotensin II (Ang II) subtype-1 receptor antagonist, losartan, on
      hemodynamics and hormonal changes in congestive heart failure by rapid
      ventricular pacing on conscious dogs. Furthermore, we characterized the Ang II
      receptors in canine heart, using the canine cardiac membrane fraction in heart
      failure. RESULTS: Acute intravenous administration of captopril improved the
      cardiac output by 19% (P < 0.01) but losartan did not, although blockade of the
      renin-angiotensin system by losartan (1.1 mumol/kg) or captopril (0.69 mumol/kg)
      induced similar changes in the plasma renin activity, norepinephrine and arginine
      vasopressin, and a similar decrease in mean arterial pressure (-10 mmHg). Renal
      blood flow was increased by either losartan or captopril. In the binding study,
      losartan produced a single displacement curve (IC50 = 0.25 mumol/l), while the
      Ang II subtype-2 (AT2) receptor antagonist PD123319 did not, indicating that the
      predominant Ang II receptor is type-1 (AT1) in canine heart. Neither the ratio of
      AT1 to AT2 receptors nor the receptor density changed with the development of
      heart failure. CONCLUSIONS: The lack of effect of losartan on cardiac output may
      be the result of its inability to block non-AT1 receptor-mediated Ang II
      activities adequately. Captopril may improve cardiac output by means of
      mechanisms not mediated by Ang II, such as locally increasing bradykinin.

PMID- 8866903
TI  - Threshold sodium excretory and renal blood flow effects of angiotensin converting
      enzyme inhibition.
AB  - OBJECTIVE: To probe the potential influence of a high renal tubular level of
      angiotensin II on sodium reabsorption using angiotensin converting enzyme
      inhibitors and a non-peptide angiotensin antagonist. METHODS: Systemic arterial
      blood pressure, renal blood flow (RBF) and electrolyte and urinary excretion were
      measured in anesthetized uninephrectomized Wistar rats. Captopril (n = 12),
      ramiprilat (n = 10) or EXP 3174 (n = 9) was infused into the renal artery in
      graded doses to examine whether the threshold dose that increased RBF was lower
      than that which increased sodium excretion rate (Na+ excretion rate). RESULTS:
      Whereas ramiprilat (0.5-4 micrograms/kg/min intra-arterially) and EXP 3174 (0.5-4
      micrograms/kg/min intra-arterially) decreased blood pressure in all but the
      lowest dose of 0.5 micrograms/kg/min, captopril (1-8 micrograms/kg/min intra
      arterially) did not change blood pressure except for a slight effect with the two
      higher doses. These three agents increased RBF to about the same degree, between
      6% and 18%, which was relatively large compared with the maximal vasodilator
      response achievable in the kidney with acetylcholine (30-37%). Captopril given
      intra-arterially had a more consistent effect on Na+ excretion rate than either
      ramiprilat or EXP 3174. An increase in Na+ excretion rate occurred with captopril
      ranging from 44% to 78%, whereas no significant change was obtained with the
      other drugs. The dose of captopril that increased RBF was the same as that which
      increased Na+ excretion rate. In those experiments in which ramiprilat resulted
      in an increase in Na+ excretion rate (five of 10 experiments), the effective dose
      was the same as that which increased RBF. CONCLUSION: When administered by the
      intra-arterial route, captopril was more effective in increasing Na+ excretion
      rate than either ramiprilat or EXP 3174. Although the threshold dose of captopril
      and ramiprilat required to increase Na+ excretion rate and RBF was similar,
      suggesting blockade of a common angiotensin II pool, there was not a good
      correlation between these two effects.

PMID- 8866904
TI  - Evidence for differences in cultured left ventricular fibroblast populations
      isolated from spontaneously hypertensive and Wistar-Kyoto rats.
AB  - OBJECTIVE: To compare fibroblast populations derived from spontaneously
      hypertensive rats (SHRLJ) and normotensive Wistar-Kyoto rats (WKYLJ) for
      angiotensin II receptor binding, gene expression of the AT1 receptor and
      angiotensinogen, hormone responsiveness and phenotypic changes. METHODS:
      Fibroblasts were isolated by either collagenase B or collagenase P and grown to
      confluency in the presence of 10% fetal bovine serum. Angiotensin II receptor
      binding was assessed under both serum and serum-free conditions. Hormonal
      treatment of cells was conducted in a serum-free background. The concentrations
      of AT1 receptor and angiotensinogen messenger RNA (mRNA) were determined by
      liquid hybridization. Phenotypic changes in fibroblast populations were analysed
      by visualization of lipid-containing vacuoles (oil red O stain) or of alpha
      smooth muscle actin-containing fibres (immunostain). RESULTS: SHRLJ collagenase-B
      cells grew more slowly and had nearly twofold fewer angiotensin II receptors than
      WKYLJ cells as measured by both radioligand binding and AT1 mRNA content (SHRLJ
      1.34 +/- 0.05 versus WKYLJ 5.94 +/- 0.41 pg mRNA per microgram total RNA) but
      contained significantly more angiotensinogen mRNA (SHRLJ 147 +/- 12 versus WKYLJ
      98 +/- 8 fg mRNA per microgram total RNA). Collagenase-P cells from the two
      strains exhibited similar binding and growth properties. Collagenase-B
      fibroblasts also exhibited greater responses to exogenous steroids, including a
      greater shift towards an adipocyte phenotype, than collagenase-P cells. Exogenous
      angiotensin II promoted transformation towards a myofibroblast cell type,
      especially in collagenase-P SHRLJ cells. CONCLUSION: Our results indicate that
      subsets of fibroblasts that differ in growth rate, angiotensin II receptor
      binding, AT1 and angiotensinogen mRNA levels, structure and steroid
      responsiveness may be isolated from the left ventricle. The potential importance
      of these altered phenotypes to cardiac remodelling and hypertrophy warrants
      further examination.

PMID- 8866905
TI  - Vascular relaxation probably mediates the antihypertensive effect of a high
      potassium diet: a role for enhanced vascular Na,K-ATPase activity.
AB  - OBJECTIVE: to evaluate the effect of dietary potassium on blood pressure and
      vascular contractility in adult rats of two strains, spontaneously hypertensive
      rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. DESIGN: 'Potassium-induced
      relaxation' was evaluated in aortic rings as a functional measure of Na,K-ATPase
      activity in the vascular wall. The rats were fed one of three diets: regular
      (American Institute of Nutrition-76 rat chow); high-sodium (7% sodium chloride)
      or high-sodium plus potassium (7% sodium chloride and 13.4% potassium citrate)
      for 12 +/- 1 weeks. RESULTS: SHR fed the high-sodium diet had a mean blood
      pressure of 157 +/- 8 mmHg, as compared with 130 +/- 9 mmHg for those on a
      regular diet (P < 0.01). SHR fed the potassium-supplemented diet had a blood
      pressure of 122 +/- 9 mmHg (P < 0.01 versus the high-sodium diet group). The mean
      blood pressure of WKY rats was 78 +/- 3 mmHg and did not differ among the dietary
      groups. The 'potassium-induced relaxation' response of aortic rings from SHR and
      WKY rats fed a potassium-supplemented diet was significantly higher (P < 0.05)
      than that in animals in the corresponding high-sodium dietary group. This
      observation in potassium-supplemented rats is interpreted as indicative of
      increased Na,K-ATPase activity in the vascular wall. CONCLUSIONS: A potassium
      rich diet in SHR receiving a high sodium intake was associated with lower blood
      pressure and higher vascular Na,K-ATPase activity. A similar effect of this diet
      on vascular Na,K-ATPase was observed in WKY. We propose that the antihypertensive
      effect of a potassium-rich diet is mediated, at least in part, by stimulation of
      vascular Na,K-ATPase activity.

PMID- 8866906
TI  - Developmental regulation of transforming growth factor-beta 1 responses and
      vascular smooth muscle growth in spontaneously hypertensive rats.
AB  - OBJECTIVE: To investigate the developmental regulation of transforming growth
      factor-beta 1 (TGF-beta 1) action and the expression of TGF-beta receptors in
      vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats
      (SHR). DESIGN: TGF-beta 1 effects on proliferation and expression of TGF-beta
      receptor subtypes were compared in VSMC prepared from SHR, Wistar-Kyoto (WKY) and
      Sprague-Dawley rats of different ages. METHODS: TGF-beta 1 effects on platelet
      derived growth factor-BB (PDGF-BB)-stimulated proliferation were examined in VSMC
      isolated from SHR, WKY and Sprague-Dawley rats aged 1, 4 and 12 weeks, and from
      renal hypertensive WKY rats. TGF-beta receptors on the surface of VSMC were
      identified by affinity labelling, followed by immunoprecipitation with TGF-beta
      receptor antibodies; complexes were then analysed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. RESULTS: TGF-beta 1 inhibited by 60-80% PDGF
      BB-stimulated proliferation of VSMC from 1-week-old SHR. In 4-week-old SHR, VSMC
      were resistant to the antiproliferative action of TGF-beta 1, whereas the
      mitogenic activity of PDGF-BB was increased approximately 150% by TGF-beta 1 in
      VSMC from 12-week-old SHR. In contrast, TGF-beta 1 inhibited by 10-50% PDGF-BB
      stimulated proliferation of VSMC from age-matched WKY and Sprague-Dawley rats.
      TGF-beta isoforms (TGF-beta 1, -beta 2, -beta 3) all elicited similar growth
      responses in VSMC from SHR and WKY rats of different ages. Hypertension per se
      did not alter TGF-beta 1 effects on proliferation, as TGF-beta 1 inhibited by 30
      40% growth factor action on VSMC from control, uni-nephrectomized and one-kidney
      one-clip hypertensive WKY rats. The type I, II and III TGF-beta receptors were
      expressed on the surface of VSMC isolated from SHR of different ages. CONCLUSION:
      Alterations in TGF-beta 1 responses, which become evident in VSMC from 4-week-old
      SHR and are most prominent at 12 weeks, may be important in the development of
      vascular hypertrophy in this rat strain.

PMID- 8866907
TI  - Mechanisms of exaggerated renal sympathoinhibition during volume loading in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: This investigation examined the central portion of the cardiac volume
      receptor reflex, which mediates the exaggerated renal sympathoinhibitory response
      to isotonic saline volume loading observed in spontaneously hypertensive rats,
      and compared the findings with those in normotensive Wistar-Kyoto control rats.
      DESIGN: Wistar-Kyoto and spontaneously hypertensive rats were fed either a normal
      diet or one high in sodium chloride for 4 weeks and subjected to sinoaortic
      denervation. To evaluate the central gain of the cardiopulmonary baroreflex,
      electrical stimulation of the central portion of the cut vagus was used to
      provide a standardized stimulus that simulates activation of cardiac volume
      receptors. To evaluate central alpha 2-adrenoceptor regulation of renal
      sympathetic nerve activity, volume loading was performed in rats pretreated with
      intracerebroventricular guanabenz, which decreased the elevated basal values of
      arterial pressure, heart rate and renal sympathetic nerve activity in
      spontaneously hypertensive rats towards those of Wistar-Kyoto rats. RESULTS:
      Vagal stimulation produced frequency-dependent decreases in arterial pressure,
      heart rate and renal sympathetic nerve activity that were similar in the two
      strains of rats on either a normal- or a high-sodium diet. Volume administration
      in rats pretreated with guanabenz resulted in similar decreases in renal
      sympathetic nerve activity in the two strains of rats. CONCLUSIONS: The mechanism
      of exaggerated renal sympathoinhibition during volume administration in
      spontaneously hypertensive rats involves an alteration in central alpha 2
      adrenoceptor regulation of renal sympathetic nerve activity.

PMID- 8866908
TI  - Prevalence of insulin resistance in essential hypertension.
AB  - OBJECTIVE: To establish the prevalence of insulin resistance in hypertensive
      subjects. DESIGN AND METHODS: The euglycaemic hyperinsulinaemic clamp was
      performed in 420 hypertensive patients taking no antihypertensive medication and
      in 51 age- and sex-matched healthy controls. No subjects with known diabetes
      mellitus or fasting hyperglycaemia were included in the study. RESULTS: The mean
      value for insulin-mediated glucose uptake (M-value at clamp) in the healthy
      control group (8.2 mg/kg per min) -2 SD was chosen as the cutoff limit for
      insulin resistance (4.4 mg/kg per min). At this cutoff limit, 27% of the
      hypertensive subjects were insulin resistant (mean value 3.1 mg/kg per min in
      this group, range 0.7-4.3). A similar prevalence of insulin resistance in
      hypertensive patients was found (31%) if the 95th percentile of the non-normally
      distributed insulin sensitivity index (M/I at clamp) was used to define the
      cutoff limit for insulin resistance: (4.4 mg/kg per min)/(mU/l x 100). In the
      insulin-resistant group, 50% showed elevated levels of serum triglycerides (> 2.0
      mmol/l), 50% had abdominal obesity (waist:hip ratio > 0.95), 20% had elevated
      levels of serum uric acid (> 400 mumol/l) and 48% had low high-density lipid
      (HDL)-cholesterol levels (< 1.0 mmol/l). Half of the insulin-resistant
      hypertensives but only 20% of the non-insulin resistant group had two or more of
      these other four metabolic impairments (P < 0.001). Insulin resistance in
      hypertension was also associated with an increased heart rate (+3 beats/min
      faster than in non-insulin resistant hypertensive patients, P < 0.01), but no
      significant differences in blood pressure were found between insulin resistant
      and non-insulin resistant hypertensive patients. CONCLUSION: When insulin
      resistance was defined as an M-value at clamp of < 4.4 mg/kg per min, based on
      calculations from a healthy control sample, about 25% of a sample of hypertensive
      subjects, taking no antihypertensive treatment and with no history of diabetes
      mellitus or hyperglycaemia, was found to be insulin resistant. This group of
      insulin-resistant hypertensives also displayed a high degree of clustering of
      other metabolic impairments.

PMID- 8866909
TI  - Endothelial function of the mesenteric arteriole and mechanical behaviour of the
      carotid artery in rats with insulin resistance and hypercholesterolaemia.
AB  - OBJECTIVE: To examine whether insulin resistance and hypercholesterolaemia in
      obese Zucker rats are associated with a modification of the mechanical behaviour
      of a conductance (carotid) artery and with an altered endothelium-dependent
      response to acetylcholine of a small resistance (mesenteric) artery. DESIGN: Male
      obese Zucker rats, 6-8 months old, were compared with age-matched lean
      heterozygous and control Zucker rats. METHODS: The mechanical behaviour of the
      carotid artery was examined in anaesthetized rats by simultaneously monitoring
      the internal diameter with an A-mode ultrasonic echo-tracking device and the
      intra-arterial pressure with a computerized data-acquisition system. Furthermore,
      histometric measurements of the carotid artery were carried out after death. The
      response to acetylcholine was examined in vitro with a Mulvany dual myograph on
      precontracted isolated segments of the third-generation mesenteric artery.
      RESULTS: Obese Zucker rats exhibited high plasma insulin and cholesterol levels.
      Blood pressure was the same in the obese and control animals. There was no
      hypertrophy or change in the mechanical behaviour of the carotid arterial wall.
      Heart weight was slightly higher in the obese rats than in the controls, but
      smaller in relation to body weight. The relaxation to acetylcholine was
      significantly attenuated in isolated small mesenteric arteries obtained from the
      obese strain. CONCLUSION: Hyperinsulinaemia and hypercholesterolaemia in obese
      Zucker rats are associated with an abnormal response to acetylcholine in the
      mesenteric arterioles. This metabolic state does not, however, alter the
      mechanical behaviour or the geometry of the carotid artery.

PMID- 8866910
TI  - A randomized study of quality of life during multiple risk factor intervention in
      treated hypertensive men at high cardiovascular risk.
AB  - OBJECTIVE: To examine the effect on quality of life in hypertensive men of a
      multiple risk factor intervention programme compared with that of usual care.
      DESIGN: A prospective, open, randomized, parallel-group study with allocation
      either to a comprehensive multiple risk factor modification programme or to usual
      care. SETTING: An outpatient clinic in a city hospital. PATIENTS: Five hundred
      and eight treated hypertensive men, aged 50-72 years, with at least one of the
      following: serum cholesterol > or = 6.5 mmol/l, smoking habit or diabetes
      mellitus. INTERVENTION: Nutritional advice, behavioural treatment principles and
      drug therapy. MAIN OUTCOME MEASURES: Minor symptoms evaluation profile (MSEP) was
      used to measure change in quality of life. RESULTS: The intervention programme
      led to sustained effects on lifestyle-related variables such as
      hypercholesterolaemia, body mass index and smoking habits, whereas diastolic
      blood pressure and HbA1c remained unchanged. The change in the MSEP during follow
      up did not differ between the intervention and the usual care groups. There was a
      close relationship between the measurements of the three MSEP dimensions at
      baseline and at follow-up (P < 0.0001). None of the potential risk factors
      measured at entry was significantly associated with change in the three MSEP
      dimensions during follow-up. CONCLUSION: The multiple risk factor intervention
      programme directed towards smoking habits, hypercholesterolaemia and the
      metabolic control of diabetes mellitus in treated hypertensive men at high
      cardiovascular risk was not associated with an impaired quality of life compared
      with that in a control group. The method used, the MSEP, has previously been
      found to be a reliable method with good validity, and this study's results
      provide further evidence of its validity.

PMID- 8866911
TI  - Angiotensin converting enzyme insertion-deletion polymorphism in Chinese.

PMID- 8866912
TI  - Trans-bilayer movement of erythrocyte membrane cholesterol in human essential
      hypertension.

PMID- 8866913
TI  - Bibliography of the current world literature in hypertension.

PMID- 8866914
TI  - Caffeine as a metabolic probe: NAT2 phenotyping.
AB  - 1. Caffeine has been used to determine acetylator phenotype for some 15 years but
      the interpretation of metabolic ratios with this substance raises theoretical and
      methodological issues. 2. N-acetyltransferase type 2 (NAT2) status was assessed
      in 23 young healthy subjects using both caffeine overnight and spot urine
      samples, and sulphadimidine. 3. Frequency distribution analysis of the metabolic
      ratios of NAT2, indicated two distinct groups for sulphadimidine, and for
      caffeine spot but not overnight samples. Spearman's rank correlation values were
      low indicating differences between the data sets for sulphadimidine and spot
      caffeine samples. Correlation between the two urine collection periods for
      caffeine was poor. 4. The complex metabolism of caffeine may compromise its value
      as a probe for determining acetylator phenotype until the effects of important
      variables are better understood.

PMID- 8866915
TI  - Pharmacokinetic evaluation of proguanil: a probe phenotyping drug for the
      mephenytoin hydroxylase polymorphism.
AB  - 1. Proguanil (PG) oxidative metabolism to cycloguanil (CG) has been linked to the
      CYP2C19-mediated genetic polymorphism in S-mephenytoin oxidative metabolism. In
      many countries, rac-mephenytoin can no longer be administered to humans and hence
      proguanil may be a more suitable probe for phenotyping purposes. 2. There are
      limited data on the pharmacokinetics of PG and CG and in particular, whether
      there is a relationship between the urinary metabolic ratio of PG and its partial
      intrinsic clearance to CG. 3. The disposition of a 100 mg oral dose of PG was
      investigated in 10 subjects with widely varying metabolic ratios (pre-study
      urinary metabolic ratio CG to PG = 0.068 to 1.11). Blood samples and all urine
      were collected for 96 h and assayed for PG and CG by h.p.l.c. 4. The urinary
      recovery of PG ranged from 30 to 69% of the dose and for CG from 2.8 to 32% of
      the dose. The overall urinary recovery of PG plus CG ranged from 54 to 77% of the
      dose. The AUC for PG ranged from 3.2 to 9.5 mg l-1 h whereas for CG it was from
      0.02 to 0.71 mg l-1 h. The partial intrinsic clearance to CG ranged 25-fold from
      0.41 to 10.1 l h-1. 5. There was a highly significant (r2 = 0.96, P < 0.001)
      relationship between the urinary metabolic ratio for PG (as CG/PG) and its
      partial intrinsic clearance to CG. 6. These data have provided evidence for the
      justification of the use of the urinary metabolic ratio of proguanil for
      population phenotyping purposes, provided systematic variation in renal drug
      clearance between populations is considered.

PMID- 8866916
TI  - In vitro interaction of the antipsychotic agent olanzapine with human cytochromes
      P450 CYP2C9, CYP2C19, CYP2D6 and CYP3A.
AB  - 1. The ability of olanzapine to inhibit the metabolism of marker catalytic
      activities for the cytochromes P450 CYP3A, CYP2D6, CYP2C9, and CYP2C19 was
      examined. This inhibitory capability was compared with that obtained with
      clozapine and known inhibitory compounds for the same cytochromes P450. 2.
      Olanzapine, clozapine, and ketoconazole were all found to non-competitively
      inhibit 1'-hydroxy midazolam formation, form selective for CYP3A, yielding Ki
      values of 491, 99 and 0.11 microM, respectively. The 1'-hydroxylation of
      bufuralol, form selective for CYP2D6, was competitively inhibited by olanzapine
      (Ki = 89 microM), clozapine (Ki = 19 microM), and quinidine (Ki = 0.03 microM).
      Tolbutamide metabolism to 4-hydroxy tolbutamide, form selective for CYP2C9, was
      competitively inhibited by clozapine and phenytoin (Ki of 31 microM and 17
      microM, respectively). Olanzapine non-competitively inhibited tolbutamide
      metabolism with a Ki of 715 microM. The marker catalytic activity for CYP2C19
      mediated metabolism, 4'-hydroxy S-mephenytoin formation, was competitively
      inhibited by clozapine (Ki = 69 microM) and omeprazole (Ki = 4.1 microM). Non
      competitive inhibition of CYP2C19 mediated metabolism was seen with olanzapine
      with a Ki of 920 microM. 3. The calculated percent inhibition by olanzapine of
      substrates metabolized by CYP3A, CYP2D6, CYP2C9, and CYP2C19 was modeled assuming
      a total plasma concentration in the therapeutic range (0.2 microM). Total
      olanzapine vs unbound olanzapine was used to model the worst case (most
      conservative) situation. In all cases, the calculated percent inhibition of these
      cytochromes P450 by olanzapine was < 0.3%, suggesting that there would be little
      in vivo inhibition of the metabolism of substrates of these enzymes when co
      administered with olanzapine.

PMID- 8866917
TI  - Identification of drugs inhibiting the in vitro metabolism of tacrolimus by human
      liver microsomes.
AB  - 1. Tacrolimus, an immunosuppressive macrolide, is metabolized by enzymes of the
      cytochrome P450 3A subfamily. In this study, 34 drugs were tested for their
      interactions with tacrolimus metabolism by human liver microsomes. 2. Fifteen
      drugs which inhibit the in vitro metabolism of tacrolimus were identified:
      bromocriptine, corticosterone, dexamethasone, ergotamine, erythromycin,
      ethinyloestradiol, josamycin, ketoconazole, miconazole, midazolam, nifedipine,
      omeprazole, tamoxifen, troleandomycin and verapamil.

PMID- 8866918
TI  - Theophylline population pharmacokinetics from routine monitoring data in very
      premature infants with apnoea.
AB  - 1. Theophylline is commonly used in neonatology for the treatment and prophylaxis
      of apnoea of prematurity, and during ventilator weaning. 2. NONMEM was used to
      study the population pharmacokinetics of intravenous and oral theophylline from
      retrospective drug monitoring data in 82 premature neonates, weighing < 1500 g at
      birth, and < or = 32 weeks gestational age. 3. Clearance (CL), volume of
      distribution (V), and oral bioavailability (F1) from liquid preparations were
      modelled alone, and under the influence of demographic and clinical covariates,
      assuming a 1-compartment model with first-order elimination. 4. The final
      population models with influential co-variates were as follows: CL (1h-1) =
      0.0000123 *body weight (g) + 0.000377 *postnatal age (days); V (1) = 0.000937
      *body weight (g); F = 0.918. 5. The CL was lower and V was higher than previously
      reported for less premature neonates, term babies, and older children. 6.
      Predictive performance of the population models was evaluated by Bayesian
      forecasting in a similar, but independent cohort of 30 infants. There was
      statistically insignificant bias and imprecision between measured and predicted
      serum theophylline concentrations. 7. Based on the validated population models,
      recommended maintenance theophylline dosages are provided for infants aged
      between 2 and 50 days, and weighing 700 to 2000 g.

PMID- 8866919
TI  - Stereoselective sulphate conjugation of salbutamol by human lung and bronchial
      epithelial cells.
AB  - 1. The metabolism of (+)-, (-)- and (+/-)-salbutamol by sulphoconjugation was
      determined in vitro using human lung cytosol and bronchial epithelial BEAS-2B
      cell homogenate. 2. For the lungs the intrinsic clearance (Vmax/Km) value for the
      pharmacologically active (-)-salbutamol (0.49 +/- 0.32 ml min-1 g-1 protein)
      exceeded that of (+)-salbutamol (0.046 +/- 0.028 ml min-1 g-1 protein) by 11
      fold. This was mainly due to a difference in Km value, which was 16 times higher
      for (+)-salbutamol (1300 +/- 170 microM) than for (-)-salbutamol (83 +/- 12
      microM). 3. The stereoselectivity of sulphoconjugation of salbutamol was very
      similar in the BEAS-2B cells, although the absolute activity was considerably
      lower. 4. The enzyme catalyzing this reaction both in the lungs and in the BEAS
      2B cells was the monoamine (M) form phenolsulphotransferase. 5. These
      observations emphasize that the smooth muscle of the bronchi most likely are
      exposed to considerably higher concentrations of the potentially toxic (+)
      enantiomer than of the bronchodilating (-)-enantiomer during therapy with (+/-)
      salbutamol.

PMID- 8866920
TI  - A pharmacokinetic interaction study of didanosine coadministered with
      trimethoprim and/or sulphamethoxazole in HIV seropositive asymptomatic male
      patients.
AB  - 1. The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were
      evaluated in ten HIV seropositive asymptomatic patients as single agents and upon
      coadministration of single doses. 2. Using a randomized, balanced incomplete
      block crossover study with at least a 1-week washout period between successive
      treatments, each patient under fasting conditions received four of the following
      five treatments: 200 mg didanosine as a single agent; 200 mg trimethoprim + 1000
      mg sulphamethoxazole; 200 mg trimethoprim + 200 mg didanosine; 1000 mg
      sulphamethoxazole + 200 mg of didanosine and; 200 mg trimethoprim + 1000 mg
      sulphamethoxazole + 200 mg didanosine. 3. Serial blood and urine samples were
      collected following the administration of each treatment. Plasma and urine
      samples were analyzed using high-pressure liquid chromatography
      (h.p.l.c.)/ultraviolet assays specific for unchanged didanosine, trimethoprim
      and/or sulphamethoxazole. 4. Percent urinary recovery (%UR) and renal clearance
      (CLR) emerged as consistently affected parameters, being decreased in the case of
      didanosine (35%, P = 0.016) and trimethoprim (32%, P = 0.019) and increased in
      the case of sulphamethoxazole (39%, P = 0.079), when all three agents were
      coadministered. The magnitude of the changes in didanosine CLR and %UR values was
      no greater when both trimethoprim and sulphamethoxazole were coadministered vs
      when each single agent was given with didanosine, suggesting that any effect was
      not additive. 5. Other key parameters such as Cmax, AUC, and t1/2 for didanosine
      (1309.9 ng ml-1, 1796.9 ng ml-1 h, and 1.61 h, respectively), trimethoprim (1.96
      micrograms ml-1, 22.86 micrograms ml-1 h, and 9.03 h, respectively) or
      sulphamethoxazole (58.62 micrograms ml-1, 799.7 micrograms ml-1 h and 9.84 h,
      respectively) were not affected when didanosine was coadministered with either
      trimethoprim (didanosine: 1751.9 ng ml-1, 2158.0 ng ml-1 h, and 1.28 h;
      trimethoprim: 1.81 micrograms ml-1, 28.89 micrograms ml-1 h, and 11.4 h),
      sulphamethoxazole (didanosine: 1279.3 ng ml-1, 1793.2 ng ml-1 h, and 1.61 h;
      sulphamethoxazole: 53.57 micrograms ml-1, 732.1 micrograms ml-1 h, and 8.95 h),
      or the combination of trimethoprim and sulphamethoxazole (didanosine: 1283.7 ng
      ml-1, 1941.8 ng ml-1 h, and 1.38 h; trimethoprim: 1.59 micrograms ml-1, 26.68
      micrograms ml-1 h, and 11.3 h; sulphamethoxazole: 59.48 micrograms ml-1, 760.9
      micrograms ml-1 h, and 9.47 h). 6. Because the observed differences in CLR and
      %UR are small and not considered to be clinically relevant, it is not necessary
      to alter the dosing regimens of didanosine, trimethoprim or sulphamethoxazole
      when administered in combination to HIV seropositive patients.

PMID- 8866921
TI  - Distribution and excretion of sumatriptan in human milk.
AB  - 1. The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was
      studied in five lactating volunteer subjects with a mean age of 27.6 years and a
      mean body weight of 75 kg. Drug concentrations in milk and plasma over the
      ensuing 8 h were measured by high-performance liquid chromatography. 2. The mean
      milk:plasma ratio estimated from the areas under the milk and plasma
      concentration-time curves (AUC) was 4.9 (95% CI 4.1-5.7), indicating a
      significant transfer of sumatriptan into the milk compartment. 3. The mean total
      recovery of drug in milk was estimated to be only 14.4 micrograms (95% CI 6.1
      22.7 micrograms), or 0.24% of the 6 mg administered dose. On a weight-adjusted
      basis this corresponded to a mean infant exposure of 3.5% of the maternal dose
      (95% CI 0.3-6.7%). 4. If oral bioavailability in the infant is similar to that in
      adults (14%), the weight-adjusted infant dose is reduced to 0.49%. Furthermore,
      allowance for reduced clearance in the infant predicts an infant exposure varying
      from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. 5. Since
      sumatriptan is usually administered as a single dose at infrequent intervals, the
      low level of excretion in breast milk suggests that continued breast feeding
      following its use will not pose a significant risk to the suckling infant. Even
      this minor exposure could be largely avoided by expressing and discarding all
      milk for 8 h after the dose.

PMID- 8866922
TI  - Lack of interaction between flucloxacillin and methotrexate in patients with
      rheumatoid arthritis.
AB  - 1. The aim of the study was to examine the potential pharmacokinetic interaction
      between methotrexate and flucloxacillin. 2. Ten rheumatoid arthritis patients
      participated in the interaction study. Subjects were allocated to either
      methotrexate alone (5-15 mg per week) or methotrexate plus flucloxacillin (500 mg
      four times a day 48 h prior to sampling) in a random order. 3. There was a
      statistically, but not clinically, significant decrease in methotrexate AUC (1307
      +/- 389 vs 1212 +/- 394 micrograms l-1 h) in the presence of flucloxacillin. Cmax
      and tmax parameters for methotrexate were not significantly altered in the
      presence of flucloxacillin. 4. Data from an additional 10 rheumatoid arthritis
      patients, starting on methotrexate, were added to the data from the placebo arm
      of the interaction study and a model dependent pharmacokinetic analysis was
      performed. The plasma concentration profiles were best described by a two
      compartment model with a mean clearance of 11.9 (+/- 1.7) l h-1 and an initial
      volume of distribution of 31.2 (+/- 2.6) l. The pronounced intersubject
      variability in the pharmacokinetic parameters was not related to any of the
      available covariate information. 5. Our findings suggest that no important
      clinical interaction occurs between flucloxacillin and methotrexate in patients
      with rheumatoid arthritis.

PMID- 8866923
TI  - Hospital antibiotic prescribing successfully modified by 'immediate concurrent
      feedback'.
AB  - 1. To determine the effectiveness of ongoing immediate concurrent feedback (ICF)
      in minimizing 'inappropriate' sultamicillin or co-amoxiclav prescribing via the
      parenteral route (i.e. when the oral route was accessible and not
      contraindicated), a prospective controlled audit was carried out on hospital
      inpatients over a 20 month period. 2. After an education programme to promote
      oral rather than unnecessary intravenous (i.v.) use of sultamicillin, co
      amoxiclav and certain other drugs, an ongoing ICF strategy was instituted. 3. ICF
      entailed issue of memos on the following day to prescribers of i.v. sultamicillin
      or co-amoxiclav for inpatients in whom this route was deemed 'inappropriate', by
      a specially trained nurse using strict objective criteria. The memos recommended
      oral prescribing (particularly of co-amoxiclav, currently the less expensive
      alternative). 4. After starting ICF, there were consistent, clinically and
      statistically significant reductions in the monthly proportions of (i) admissions
      prescribed i.v. sultamicillin or co-amoxiclav (38% P < 0.001), (ii) those in whom
      the route was 'inappropriate' (75%, P < 0.001), and (iii) corresponding ratios of
      i.v./oral usage and expenditure, oral sultamicillin/co-amoxiclav usage and
      expenditure, as well as total and per admission expenditure on i.v. forms (> or =
      43%, P < 0.01). 5. For i.v. cefuroxime (for which there was no ICF) and its oral
      counterpart cefuroxime-axetil, there were no comparable changes in usage or
      expenditure. 6. This simple, ongoing ICF strategy was effective and well
      accepted; estimated net monthly savings being HK$26-30,000.

PMID- 8866924
TI  - Crossover trials are only useful when there is a positive correlation between the
      response to different treatment modalities.
AB  - 1. Trials that do not allow us to reject the null hypothesis of no treatment
      effect may have had an inappropriate design. Trials are virtually never assessed
      for correlation between responses to different treatment modalities. 2. The level
      of correlation between responses to different treatment modalities is a major
      determinant of the power of crossover trials. 3. It is relevant to assess
      correlation levels between responses to the different treatment modalities a
      priori. With a negative correlation a crossover design is likely to lack power.
      4. In 1991 the British Journal of Clinical Pharmacology published eight crossover
      trials which would have been more efficient had they been performed with a
      parallel groups design.

PMID- 8866925
TI  - Forearm vascular responses to serotonin are not mediated by products of
      cyclooxygenase.
AB  - The involvement of cyclooxygenase-derived substances in the forearm arteriolar
      responses to serotonin was determined in 10 healthy male volunteers. Serotonin
      was infused in five incremental doses (0.003-30 micrograms min-1) for 2 min each
      into the brachial artery of the non-dominant forearm. Forearm blood flow (FBF)
      responses to each dose were measured by strain-gauge venous occlusion
      plethysmography. The cyclooxygenase inhibitor indomethacin (100 mg) was
      administered orally following the serotonin infusions. After 90 min the serotonin
      infusions were repeated and FBF responses measured. Serotonin caused a biphasic
      response with vasodilatation occurring at low doses (0.003-3 micrograms min-1, P
      < 0.01) and vasoconstriction occurring at the highest dose (P < 0.01). There was
      no significant difference in vascular response to serotonin following
      cyclooxygenase inhibition. In conclusion, cyclooxygenase products are not
      involved in the forearm vascular responses to serotonin in healthy human
      subjects.

PMID- 8866926
TI  - Hydroxychloroquine relative bioavailability: within subject reproducibility.
AB  - Six healthy volunteers received hydroxychloroquine sulphate 200 mg orally on four
      occasions (three tablets, one solution). Maximum hydroxychloroquine blood
      concentration (Cmax; range 135-422 ng ml-1) and time to maximum (tmax; range 1.5
      7.0 h) for the three tablet doses showed significant differences between subjects
      (P < 0.009; between subject coefficients of variation (CVs) 34% and 27%,
      respectively). There were no within subject differences in Cmax (P = 0.32; mean
      within subject CV 11%), Cmax corrected for weight (P = 0.28) or tmax (P = 0.35;
      mean within subject CV 16%). Truncated areas under the hydroxychloroquine blood
      concentration-time curve of the three tablets were different between (P = 0.0001)
      but not within subjects (P = 0.13). Again, between subject CV (38%) was more than
      three times the mean within subject CV (12%). Bioavailability was not limited by
      tablet formulation. The significant variability in relative bioavailability
      between but not within individuals indicated that individualising dosing to
      target concentrations associated with optimal outcomes may minimise variability
      in response.

PMID- 8866927
TI  - Lung bioavailability of chlorofluorocarbon free, dry powder and
      chlorofluorocarbon containing formulations of salbutamol.
AB  - With the future advent of a world wide ban on chlorofluorocarbon containing
      aerosols, a study was designed to compare the in vivo lung bioavailability of
      salbutamol via chlorofluorocarbon-containing metered-dose inhaler (CFC),
      chlorofluorocarbon-free metered-dose inhaler (CFC-free), and dry powder inhaler
      (DPI). Twelve healthy male subjects were given 1200 micrograms salbutamol and
      measurements made of plasma and urinary salbutamol. CFC-free produced
      significantly higher plasma salbutamol levels (ng ml-1; mean and 95% CI for
      difference) than either CFC or DPI: Cmax, CFC-free 4.18 vs CFC 3.29 (95% CI 0.10
      1.68), vs DPI 3.42 (95% CI -0.03-1.56). The ratio for the difference in Cmax
      between CFC and CFC-free formulations was 1.32 (95% CI 1.02-1.61). There were no
      significant differences between CFC and DPI formulations. Urinary salbutamol
      results did not reveal any significant differences between the three inhalers
      (micrograms 30 min-1): CFC-free 42.4, CFC 43.8, DPI 45.3. Thus, the lung
      bioavailability of CFC-free was greater than that of CFC or DPI formulations of
      salbutamol.

PMID- 8866928
TI  - Systemic absorption of nebulized morphine compared with oral morphine in healthy
      subjects.
AB  - The inhalation of nebulized morphine has been advocated to treat dyspnoea and
      pain in patients with cancer. We have compared plasma morphine concentrations in
      healthy volunteers after nebulized (50 mg in 4 ml saline), oral (10 mg solution)
      and intravenous (5 mg) morphine sulphate. Bioavailability was estimated by
      dividing the morphine concentration AUC/dose by that obtained after intravenous
      morphine. Peak plasma morphine concentrations were achieved more rapidly after
      nebulized than oral morphine, occurring within 10 min in all subjects. The
      systemic bioavailabilities of morphine (mean +/- s.d.) were 5 +/- 3% and 24 +/-
      13% for the nebulized and oral routes respectively. Nebulization is a rapid but
      inefficient method of administering morphine. It may provide more rapid pain
      relief compared with oral morphine but clinical studies are needed to confirm
      this.

PMID- 8866929
TI  - The use of medication and alcohol among the Spanish population.
AB  - The 1993 Spanish National Health Survey data were used to estimate how frequently
      both medication and alcohol were used among 21,084 people over 16 years of age. A
      total of 47.1% of the population, especially women and an increasingly older
      section, had taken some kind of medication during the previous fortnight. A total
      of 9.8% of the population took medication and alcohol together. This was more
      frequently observed among men than among women, and especially so among the older
      age groups. These data reveal that concomitant alcohol and medication use is
      frequent among the Spanish population, and suggest a need to devote much more
      attention to this potential problem.

PMID- 8866930
TI  - Pupillary response to topical tropicamide as a marker for Alzheimer's disease.
AB  - The mydriatic response to eyedrops of the anticholinergic drug tropicamide at
      very low concentration (0.01%) was studied in subjects with Alzheimer's disease
      (AD, n = 10) and multi-infarct dementia (MID, n = 10). There was no significant
      difference in pupillary response between the two groups. The test is unlikely to
      be useful in differentiating different types of dementia.

PMID- 8866931
TI  - Chronic treatment with eltoprazine does not lead to tolerance in its anti
      aggressive action, in contrast to haloperidol.
AB  - The behavioral effects of eltoprazine and haloperidol during a 4 week treatment
      period were studied in the resident-intruder model of aggression in male rats.
      Eltoprazine, a serotonergic (5-HT1A/1B) agonist with specific anti-aggressive
      actions in animals, was compared to haloperidol, a neuroleptic often used to
      control behavioral disorders. Eltoprazine (1 or 3 mg/kg p.o.) and haloperidol (2
      mg/kg p.o.) were given 60 min before a 10 min aggression test. Acutely,
      eltoprazine reduced aggression, without adversely affecting other behaviors.
      Eltoprazine (1 or 3 mg/kg p.o.) was subsequently given daily for 4 weeks and
      aggression tests were performed each week. The anti-aggressive effects of
      eltoprazine remained stable over the period of 4 weeks whereas exploration was
      increased. After a wash-out period of 1 week aggression had returned to baseline
      levels. Acutely given, haloperidol (2 mg/kg p.o.) completely reduced aggression
      concomitant with massive sedation. Significant tolerance developed to the
      sedatory actions of haloperidol over the 4 week treatment period. Aggression
      returned slowly, but remained below baseline values. One week after wash-out a
      new challenge with haloperidol (2 mg/kg p.o.) revealed significant tolerance.
      After 2 weeks wash-out aggression had returned to baseline. The data demonstrate
      persistent and specific anti-aggressive effects after eltoprazine showing no
      tolerance. In contrast, haloperidol showed tolerance and rebound effects for
      aggression. The development of tolerance after haloperidol has a different course
      for sedation than for the anti-aggressive action.

PMID- 8866932
TI  - Antidepressant induced mania in obsessive compulsive disorder.
AB  - Five cases of obsessive compulsive disorder (OCD) and antidepressant
      (clomipramine, fluoxetine and citalopram) treatment emergent manic symptoms are
      presented. This is of relevance in terms of management, and may suggest an
      association between OCD and bipolar disorder.

PMID- 8866933
TI  - A controlled trial with ORG 2766, an ACTH-(4-9) analog, in 50 relatively able
      children with autism.
AB  - The aim of the present study was to replicate earlier findings of beneficial
      effects of ORG 2766, an ACTH-(4-9) analog, in autistic children. Fifty children
      with autism, 7-15 years old and with a Performance IQ of more than 60,
      participated in a double-blind placebo controlled parallel trial. Active
      treatment was 40 mg ORG 2766 for 6 weeks. The outcome was assessed on the basis
      of the Aberrant Behavior Checklist completed by parents and teachers, and by
      means of a detailed behavioral observation (30 subjects). ORG 2766 failed to
      improve social and communicative behavior at a group level. The rate of
      individual response, defined as a reliable change in social withdrawal at home
      and at school, to ORG 2766 (10 out of 30) and placebo (4 out of 20) was not
      significant either. The children who responded to ORG 2766, but not those who
      responded to placebo, manifested significant improvements outside the changes in
      the defining variables, including a decrease in hyperactivity at school. The
      responders to ORG 2766 were characterized mainly by a relatively lower PIQ;
      further by more initial hyperactivity, stereotypies and abnormal speech, and less
      initial eye contact. The responders to placebo could not be differentiated from
      the non-responders to placebo. Future studies should examine whether ORG 2766
      differentially affects various subtypes of autism.

PMID- 8866934
TI  - Mechanical lesions of the fimbria fornix in rat brain studied by 1H-magnetic
      resonance imaging. Evidence for long-lasting dynamic alterations in the
      ipsilateral ventricular system.
AB  - In vivo 1H-NMR imaging was employed to study dynamic changes in the status of
      tissue water as a function of time after mechanical brain injury induced by
      partial unilateral transection of the fimbria fornix (FF) in the rat brain and
      was correlated with histology. Changes in the brain tissue were reproducibly
      found in distinct regions which were exclusively located in the lesioned
      hemisphere. The most pronounced changes concerned the lateral ventricle.
      Ventricular enlargement became evident posterior to the site of transection after
      a few hours and was maximal after 2-4 days. At later time points the posterior
      ventricular expansion was reduced. The lateral ventricle anterior to the site of
      transection was significantly enlarged from day 1 and continued to expand for up
      to 7 months. Tissue response at the site of transection, mainly involving the
      hippocampal formation and the thalamus, was first manifested after 24 h, while
      signs of progressive tissue degeneration were apparent in the long term.

PMID- 8866935
TI  - Differential actions of typical and atypical antipsychotic drugs on dopamine
      release in the core and shell of the nucleus accumbens.
AB  - The effects of acute administration of typical and atypical antipsychotic drugs
      on extracellular dopamine (DA) concentrations in brain were examined in two
      subdivisions of the nucleus accumbens (NAC), the core and the shell, which are
      largely associated with motor control and limbic functions, respectively, by
      using in vivo differential normal pulse voltammetry in anesthetized, pargyline
      pretreated rats. The following drugs were studied: haloperidol (0.1 and 1.0
      mg/kg), clozapine (1.0 and 5.0 mg/kg), amperozide (1.0 and 2.0 mg/kg),
      risperidone (0.1 and 1.0 mg/kg), the selective 5-HT2A/5-HT2C receptor antagonist
      ritanserin (1 mg/kg) and the selective DA-D2/D3 receptor antagonist raclopride
      (10 and 320 micrograms/kg). Drugs with predominantly high 5-HT2 receptor
      antagonistic action, such as amperozide and ritanserin, as well as low doses of
      either risperidone or clozapine increased DA concentrations to a greater extent
      in the shell than in the core subdivision of the NAC. In contrast, drugs with a
      more potent D2 receptor antagonistic action, such as haloperidol and raclopride,
      as well as high doses of either risperidone or clozapine, elicited a larger DA
      increase in the core than in the shell. Consequently, atypical antipsychotics
      characterized by potent 5-HT2 receptor antagonism can be differentiated from
      typical antipsychotic drugs on the basis of their preferential effect on DA
      transmission in the shell region of the NAC.

PMID- 8866936
TI  - Phorbol ester intracerebroventricularly induces a behavioral hypoactivity that is
      not affected by chronic or acute lithium.
AB  - Chronic lithium treatment in rats has been reported to decrease protein kinase C
      alpha isozyme in hippocampal membranes. We gave phorbol ester, a protein kinase C
      activator, i.c.v. to rats treated with acute or chronic lithium. Low dose phorbol
      ester causes a marked hypoactivity and high dose phorbol ester causes a barrel
      rolling behavior, but no behavioral interactions with lithium treatment were
      observed.

PMID- 8866937
TI  - Analgesic effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS) in patients with
      chronic pain.
AB  - Previous pharmacological studies using animals indicated that a systemic
      administration of L-threo-3,4-dihydroxy-phenylserine (L-DOPS), a precursor of
      noradrenaline, induces an antinociceptive effect and an increase in the CNS level
      of noradrenaline which serves an inhibitory role at the spinal dorsal horn and
      the supraspinal pain afferent system. The aim of the present study was to
      investigate the analgesic effect of L-DOPS in patients with chronic pain. We
      selected 18 patients with various kinds of pain. In nine patients, L-DOPS
      (tablets) was orally administered and pain was assessed by the visual analogue
      scale (VAS) before and after the L-DOPS administration. Administration of L-DOPS
      resulted in dose-dependent analgesia. The maximum analgesia (VAS change: from 10
      to 4.1 +/- 0.9) was observed 60 min after an administration of 100 mg and it
      lasted for 2-5 h depending on the patient. In the other nine patients, oral
      administration of placebo tablets produced only a slight analgesia (VAS change:
      from 10 to (9.2 +/- 0.3). The difference between the L-DOPS-induced effect and
      the placebo-induced one was statistically significant. After repeated
      administration of L-DOPS for 4-5 weeks, neither tolerance nor side effects were
      observed.

PMID- 8866938
TI  - Do G proteins have a role in antidepressant actions?

PMID- 8866939
TI  - The effects of repeated administration of diazepam, MK-801 and CGP 37849 on rat
      behavior in two models of anxiety.
AB  - The effects of repeated administration of diazepam, MK-801 and CGP 37849 on rat
      behavior in the Vogel conflict test, and in the open field test of neophobia,
      were studied in rats. The drugs were given at doses active acutely, for 5 days,
      the last dose was administered 30 or 60 min prior to testing. It appeared that
      diazepam and MK-801 treated animals showed clear-cut signs of behavioral
      tolerance and motor sensitization, respectively. CGP 37849 was characterized by
      the best pharmacological profile, in that on repeated administration the drug not
      only retained its anxiolytic-like potency in the Vogel test, but even enhanced
      rat exploratory behavior in a new environment, independently of changes in animal
      motor activity. Repeated injections of the examined agents did not cause any
      significant modifications in monoamine levels and their turnover rates, in the
      striatum and limbic forebrain. It is concluded that the new class of competitive
      NMDA receptor antagonists, exemplified by CGP 37849, is the most promising
      candidate for clinical trials in anxiety disorders.

PMID- 8866940
TI  - Enhancement of morphine self-administration in drug naive, inbred strains of mice
      by acute emotional stress.
AB  - The primary reinforcing effect of morphine was compared in two genetically inbred
      strains of mice (C57BL/6 and DBA/2) using the intravenous self-administration
      procedure in drug naive animals. The morphine self-administration differed
      between the mouse strains. DBA/2 but not C57BL/6 acquired self-administration of
      morphine with a bell-shaped unit dose-response curve. Acute physical stress
      induced by electrical footshocks did not significantly affect the self
      administration in both strains. Acute emotional stress induced by forcing mice to
      witness another mouse being subjected to acute physical stress caused a shift of
      the bell-shaped unit dose-response curve of morphine self-administration to the
      left in the DBA/2 mice. The C57BL/6 mice, which initially failed to demonstrate
      stable self-administration, started to self-administer morphine after emotional
      but not physical stress. Emotional distress may increase the individual
      sensitivity to the rewarding effects of morphine and may render an individual
      more susceptible to development of drug dependence.

PMID- 8866941
TI  - Fluvoxamine increases the clozapine serum levels significantly.
AB  - In this case report we describe an interaction between clozapine and fluvoxamine
      in two physically healthy patients meeting the DSM-IIIR criteria for paranoid
      schizophrenia. The substantial rise of clozapine serum levels suggest that
      caution should be exercised when combining fluvoxamine with clozapine as the
      clozapine concentration may increase by a factor of 5-10.

PMID- 8866942
TI  - Differential uptake of myo-inositol in vivo into rat brain areas.
AB  - Oral inositol has been reported to have antidepressant and antipanic properties
      in humans. Inositol enters the brain poorly and high doses are required. Natural
      uptake processes and specific transporters are involved. We here report that
      intraperitoneally administered inositol is taken up differently by various brain
      areas and that brain areas have different baseline inositol levels. These effects
      could be important in understanding the differential effects of lithium-induced
      lowering of inositol and of behavioral effects of exogenous inositol.

PMID- 8866943
TI  - ECNP position paper on social phobia proceedings from an ECNP workshop in
      Jerusalem, October 1994.

PMID- 8866944
TI  - Cocaine-induced behavioral sensitization: effects of haloperidol and SCH 23390
      treatments.
AB  - The objective of this study was to determine whether the development of
      behavioral sensitization to cocaine could be prevented by high doses of the
      dopamine receptor antagonists haloperidol and SCH 23390. In two experiments, male
      Wistar rats were injected daily for 4 days with either cocaine (15 mg/kg, IP) or
      vehicle in combination with haloperidol (1.0 mg/kg, IP), SCH 23390 (0.5 mg/kg,
      SC), or vehicle. After the daily injections, the rats were tested for locomotor
      activity in photocell arenas. At 24 h after the last preexposure test session,
      all rats were given a challenge injection of cocaine (15 mg/kg, IP) and tested
      for activity. Cocaine treatments produced a greater relative increase in
      locomotor activity with repeated exposure compared to vehicle treatments (i.e.,
      sensitization). Moreover, the acute activating effects of cocaine over days were
      blocked by both haloperidol and SCH 23390. The coadministration of haloperidol,
      but not SCH 23390, blocked the development of behavioral sensitization to
      cocaine. That is, after the cocaine challenge injection, rats pretreated with SCH
      23390 and cocaine did not differ from rats preexposed only to cocaine, whereas
      rats pretreated with haloperidol and cocaine did not differ from rats pretreated
      only with vehicle. Pretreatment with haloperidol or SCH 23390 without cocaine
      enhanced the locomotor-activating effects of the subsequent cocaine challenge
      injection. These findings suggest that cocaine-induced behavioral sensitization
      may develop as a result of repeated dopamine D1- or D2-type receptor stimulation,
      and that brief dopamine antagonist treatments enhance subsequent behavioral
      sensitivity to cocaine.

PMID- 8866945
TI  - Place conditioning with alcohol in alcohol-preferring and -nonpreferring rats.
AB  - A place-conditioning procedure was used to examine the effect of selective
      breeding for ethanol preference on sensitivity to the rewarding and/or aversive
      effects of ethanol. On 4 alternate days, groups of seven to eight alcohol
      preferring (P) and alcohol-nonpreferring (NP) rats received IP injections of 0.0
      (saline controls), 0.5, 1.0, or 1.5 g ethanol/kg body wt. immediately before 15
      min confinement in a novel environment. On the 4 intervening days the same rats
      received saline injections before 15 min confinement in a different environment.
      On day 9, a 15-min choice test was given with no injections, in which the rats
      could move freely between the ethanol and the saline-paired environments. Dose
      dependent avoidance of the ethanol-paired environment was observed in both lines
      of rats (1.0 and 1.5 g/kg), but the magnitude of the avoidance was less in the P
      relative to the NP rats, indicating that ethanol was less aversive for the P
      rats. No evidence for a place preference was observed in either line with any of
      the ethanol doses. An innate reduced sensitivity to the aversive effects of
      ethanol in rats of the P line and/or an enhanced sensitivity to the aversive
      effects of ethanol in rats of the NP line may contribute to the different levels
      of oral ethanol self-administration observed in these selectively bred rat lines.

PMID- 8866946
TI  - Central nervous system characterization of the new cholecystokininB antagonist
      LY288513.
AB  - The activity of LY288513, an investigational cholecystokinin (CCK)B antagonist,
      was evaluated in a wide range of pharmacological tests in mice and rats. The
      anxiolytic benzodiazepine, diazepam, served as a reference standard for LY288513
      in many of the tests. In the elevated plus-maze, LY288513 (3, 10 mg/kg, IP; 10,
      30 mg/kg, PO) produced an anxiolytic-like action in mice with a magnitude of
      effect similar to that of diazepam. However, unlike diazepam, LY288513 produced
      no overt clinical signs and did not affect muscle tone, neuromuscular
      coordination, or sensorimotor reactivity. Also, in contrast to diazepam, LY288513
      did not produce changes in the thresholds for electroshock- or pentylenetetrazol
      induced convulsions. High doses of LY288513 (1000 mg/kg, PO) were required to
      reduce spontaneous activity levels, decrease body temperature, or potentiate the
      CNS-depressant effects of hexobarbital. LY288513 had no analgesic activity in
      mouse writhing or tail-flick tests. Electrophysiological studies in anesthetized
      rats showed that acute administration of LY288513 decreased the number of
      spontaneously active dopamine neurons in the substantia nigra and ventral
      tegmental area. However, LY288513 did not produce catalepsy. These data indicate
      that LY288513 possess both anxiolytic and antipsychotic potential.

PMID- 8866947
TI  - Audiogenic and audiogenic-like seizures: locus of induction and seizure severity
      determine postictal prolactin patterns.
AB  - Audiogenic seizures (AS) are a model of generalized tonic-clonic seizures, evoked
      by high-intensity (110 dB) acoustic stimulation evaluated by means of behavioral
      severity indexes (SI). Postictal prolactin (PRL) is a marker of generalized
      seizures, both in animals and humans. Thus, in the present work we assayed
      postictal PRL in a) male Wistar AS susceptible (S, n = 5) and AS resistant (R, n
      = 13) rats made susceptible by specific midbrain lesions. b) In rats electrically
      stimulated in the central nucleus (CN) of the inferior colliculus (IC) (n = 20),
      or the cortical IC (CxIC, n = 18). In c) S rats pretreated with either
      bromocriptine (BRO; 4 mg/kg; SC), a PRL release inhibitor, or vehicle (V), 30 min
      before the electrical stimulation. Basal PRL was 2-10 ng/ml at time 0. In the S
      group, only animals with generalized seizures presented a postictal PRL elevation
      between 5 and 15 min (60-90 ng/ml; p < 0.05). R rats displayed a discrete PRL
      response lower than that of S animals. CxIC stimulation produced more severe
      seizures and greater postictal PRL enhancement than CNIC stimulation, always
      raising at 5-15 min (p < 0.01). BRO blocked the PRL increase even in the presence
      of higher seizure scores (p < 0.02). The positive correlation between seizure
      intensity (SI values), site of initiation (central or cortical IC nuclei), and
      postictal PRL patterns makes this a reliable model for studying the
      neurochemistry of the postictal phase and the interaction between hormones and
      epilepsy.

PMID- 8866948
TI  - Individual differences in reactivity to the rewarding/aversive properties of
      drugs: assessment by taste and place conditioning.
AB  - The ability of individual differences in the strength of conditioned taste
      avoidance (CTA) to predict strength of place conditioning produced by the same
      drug was assessed. In Phase 1, rats were assigned to High CTA and Low CTA groups
      on the basis of their intake of saccharin solution previously paired with
      morphine, amphetamine, lithium, or fenfluramine. In Phase 2, the rats received
      place conditioning training with the same drug used during Phase 1. The rats that
      displayed the strongest amphetamine-induced CTA also displayed the strongest
      amphetamine-induced place preference, suggesting that a common mechanism mediates
      both effects. On the other hand, the strength of the CTA was unrelated to the
      strength of the place preference or place aversion produced by morphine, lithium,
      or fenfluramine.

PMID- 8866949
TI  - The effects of two chronic intermittent stressors on brain monoamines.
AB  - The effects of chronic exposure (27 days) to two different stressors on brain
      monoaminergic activity was studied in adult male rats. The stressors used were
      restraint in tubes (RES) and immobilization in wooden boards (IMO). Both
      chronically stressed and stress naive (control) rats were subjected to 0, 15, and
      60 min of the same stressor to which they were chronically exposed. Previous
      chronic exposure to either RES or IMO significantly reduced ACTH response to the
      same stressor. Monoaminergic response to these stressors was studied by measuring
      the levels of noradrenaline (NA), serotonin (5-HT) and their metabolites: 3
      methoxy,4-hydroxyphenyletileneglycol sulfate (MHPG-SO4) and 5-hydroxyindoleacetic
      acid (5-HIAA), respectively. The regions studied were: pons plus medulla,
      midbrain, hypothalamus, hippocampus, and frontal cortex. Previous chronic
      exposure to the stressors induced only few changes in the resting levels of the
      monoamines and their metabolites. In addition, monoaminergic response to the same
      stressor to which they were chronically exposed was always similar in control and
      chronically stressed rats. These data indicate that brain NA and 5-HT metabolism
      is less sensitive than ACTH to the process of habituation to a repeated stressor,
      at least in the gross areas of the brain analyzed in the present study.

PMID- 8866950
TI  - Influence of eticlopride on cocaine- and DA D2 agonist-induced behavioral effects
      in rats.
AB  - The influence of the DA D2 antagonist (-) eticlopride on cocaine- and DA D2
      agonist-induced behavioral effects was investigated by means of two series of
      experiments, in rats. In the first 10-day series, coadministration of (-)
      eticlopride (10 and 50 micrograms/kg, SC) always potently inhibited cocaine (15
      mg/kg, IP)-induced hypermotility but did not modify the penile erection (PE)
      enhancement produced by the drug at the first injection; it actually counteracted
      the inhibitory effect of subchronic cocaine on PE. In the second series, (-)
      eticlopride, at the same doses, antagonized PE elicited by various DA D2 agonists
      at nonstereotyping doses; when, along with PE, stereotyped behavior was induced,
      only the latter was inhibited by (-) eticlopride, which even increased PE.

PMID- 8866951
TI  - Effect of social isolation on the reinforcing properties of morphine in the
      conditioned place preference test.
AB  - It is widely accepted that early environmental influences may affect the
      behaviour of the adult animal and the responsivity to psychotropic drugs.
      Isolation rearing is an important variable in this regard. The present
      experiments compared the effects of isolation and social rearing of rats on the
      reinforcing properties of morphine. Male Lister hooded rats were raised from
      weaning either alone (isolation reared rats) or in groups of four rats per cage
      (socially reared rats). Four weeks later, the rats were tested for their
      sensitivity to morphine using a conditioned place preference test. Comparisons
      were made between socially and isolation-reared rats with respect to
      preconditioning and postconditioning following either saline or morphine (1 and 5
      mg/kg SC) pretreatment. The results from the preconditioning phase demonstrated
      that rats reared either socially or in isolation had least preference for one
      quadrant that was then selected as the treatment quadrant. After saline
      conditioning, the socially reared rats still showed a significant (p < 0.05) less
      preference for the treatment quadrant relative to the opposite quadrant.
      Following morphine (1 and 5 mg/kg) conditioning, socially reared rats spent
      significantly more time (p < 0.05) in the treatment quadrant relative to the
      opposite quadrant, whereas isolation-reared rats failed to display morphine
      induced place preference. These results demonstrate that social isolation
      decreases the reinforcing properties of morphine.

PMID- 8866952
TI  - GR 127935 blocks the locomotor and antidepressant-like effects of RU 24969 and
      the action of antidepressants in the mouse tail suspension test.
AB  - The 5-HT1A/B agonist RU 24969 induces hyperactivity in rodents and also shows
      antidepressant-like effects in some animal models of depression. We have examined
      the effects of selective antagonists at 5-HT1A and 5-HT1B/D receptors (WAY 100135
      and GR 127935, respectively) on both the hyperlocomotor and anti-immobility
      effects of RU 24969. While a high dose of WAY 100135 (10 mg/kg) had no effect in
      either paradigm, GR 127935 attenuated the behavioural effects of RU 24969 in
      both. WAY 100135 was also without effect on the antidepressant effect of
      paroxetine, while GR 127935 blocked the effects of paroxetine (1 mg/kg) and
      imipramine (10 mg/kg). Furthermore, while coadministration of paroxetine or
      imipramine enhanced the effects of RU 24969 in the mouse tail suspension test,
      imipramine had no effect on the locomotor activating effects of the 5-HT1B
      agonist, suggesting different neural substrates may underly the effects in the
      different tests. These studies indicate a role for the 5-HT1B/D receptor in the
      mediation of the effects of antidepressant treatment.

PMID- 8866953
TI  - Consequences of selective blockade of septal noradrenergic afferents on anxiety
      and spatial working memory performance in mice.
AB  - This experiment was designed to investigate the role of septal noradrenergic (NA)
      afferents in the control of anxiety and spatial working memory. To this end,
      C57Bl/6 mice were infused bilaterally into the lateral septal nuclei with 500
      ng/0.2 microliter of BE 2254, a selective alpha 1 postsynaptic adrenoceptor
      antagonist. The consequences of this reversible treatment were evaluated 20 min
      later on the anxiety level measured in an elevated plus-maze and on spatial
      working memory, evaluated under four different conditions via the learning of a
      delayed nonmatching to place (DNMTP) rule achieved in an eight-arm radial maze.
      In these conditions, the BE 2254, as well as the saline-injected control group,
      showed an elevation of the anxiety level that may be the indirect expression of a
      nonspecific septal dysfunction induced by the vehicle injection rather than the
      normal behavioral response produced by the decrease of septal NA activity. This
      septal dysfunction also impaired spatial working memory but only when mnesic
      difficulty of the task is increased, suggesting that this impairment expresses a
      general memory deficit rather than a working memory deficit per se. A lack of
      spatial working memory deficits in BE 2254 or saline-injected animals was also
      observed in two other conditions of the behavioral protocol. However, when
      treatments were applied before the first exposure of animals to the radial maze
      (exploration session), only the group which received BE 2254 was impaired during
      the acquisition session for the rule performed 24 h later. This delayed
      perturbation seems to be linked, at this stage of the learning procedure, to the
      lack of NA-dependent processes taking place during the exploration session. Taken
      together, these data suggest that septal NA mechanisms are more essential at
      initial stage of this learning, when animals process new features of the
      situation, than during the expression of spatial working memory per se.

PMID- 8866954
TI  - Changes in energy metabolism and metabolite patterns of obese rats after
      application of dexfenfluramine.
AB  - Serotonergic neuronal networks are important for food intake and body weight
      regulation. Dexfenfluramine (dF), a serotonin releaser and reuptake inhibitor,
      was used to investigate changes in food intake, body weight development, energy
      expenditure, respiratory quotient, and substrate oxidation rates for 12 days.
      Rats, which had been made obese by early postnatal overfeeding, received an
      energy-controlled mash diet and water ad lib and were intraperitoneally injected
      daily with either saline, 5 or 10 mg dF/kg. Compared to controls, food intake,
      body weight development, and energy expenditure were decreased in a dose
      dependent manner, especially during the first 6 days. Lipid oxidation was
      increased while oxidation of carbohydrates was decreased. Pair-feeding
      experiments over 2 days revealed that this was not solely a result of diminished
      food intake but also an additional metabolic effect of dF, different from its
      anorectic effect. At the end of these experiments, plasma glucose and liver
      glycogen were unchanged after dF, but plasma free fatty acids were significantly
      decreased. Insulin-sensitivity was probably improved, indicated by decreased
      insulin levels and increases in muscle glycogen contents and activities of muscle
      pyruvate kinase. Liver-glutamine and contents of valine, leucine, and isoleucine
      in the muscle were significantly decreased after dF-treatment, the latter
      indicating a diminished proteolysis. The plasma tryptophan/large neutral amino
      acids ratio of the dF-rats was unchanged but that of the paired-fed rats was
      changed, despite similar changes in food intake. It is concluded that both
      increased oxidation of endogenous fat and reduced food intake could mediate the
      body weight reducing effect of dF.

PMID- 8866955
TI  - Effects of four antiepileptic drugs on sleep and waking in the rat under both
      light and dark phases.
AB  - Sedation is a common side effect of anticonvulsant drug therapy. To find out
      whether the new antiepileptic drugs, felbamate and lamotrigine, are able to
      produce sedation, we carried out electroencephalographic (EEG) studies in the rat
      to measure drug effects on sleep-wake patterns, during both light and dark
      phases. For comparison, the reference drugs, carbamazepine and phenobarbital,
      were also studied. EEG activity was recorded for 6 h after oral (PO)
      administration of drugs or vehicle, and the stages of wakefulness, rapid eye
      movements (REM) sleep and non-REM sleep were classified thereafter. In the light
      phase, felbamate (30-300 mg/kg) did not produce sedative effects, while
      lamotrigine (3-30 mg/kg) increased wakefulness at each dose tested. Carbamazepine
      (10-100 mg/kg) did not produce sleep-wake alterations, and phenobarbital (100
      mg/kg) markedly suppressed REM. In the dark phase, felbamate (300 mg/kg),
      lamotrigine (30 mg/kg), and carbamazepine (100 mg/kg) reduced REM but did not
      change the total amount of sleep. Phenobarbital, at 100 mg/kg, markedly increased
      total sleep and greatly reduced REM. This study shows that the anticonvulsant
      drugs examined have different effects on the states of sleep and wakefulness in
      the rat. The data are discussed on the basis of the mechanism of action that
      characterizes each individual drug.

PMID- 8866956
TI  - Investigation into the role of histamine receptors in rodent antinociception.
AB  - The aim of the present study is to the elucidate the confusion that exists in the
      literature concerning which receptor subtype is involved in mediating histamine
      antinociception. To this purpose impromidine 3HCl and burimamide were used.
      Because both substances have been described to block histamine H3-receptor, and,
      at higher doses, also to act on the postsynaptic site as agonist and antagonist,
      respectively, they were administered in a wide range of ICV doses, to distinguish
      the effects due to action on different receptors. Experiments were performed in
      mice and rats by means of tests inducing three different kinds of noxious
      stimuli: mechanical (paw pressure), chemical (abdominal constriction), and
      thermal (hot plate). Both substances showed, at the lowest doses tested,
      antinociception, which was antagonized by the selective H3-receptor agonist, (R)
      alpha-methylhistamine 2HCl (RAMH) (10 mg/kg SC in mice or 0.5 microgram per rat
      ICV). At higher doses impromidine was antinociceptive while burimamide was
      hypernociceptive, in accordance with their opposite action on the H2-receptor. It
      is suggested that the histaminergic system modulates nociception via activation
      of the H2-receptor.

PMID- 8866957
TI  - Ontogeny of striatal dopamine release in rats after acute administration of
      methamphetamine.
AB  - In the present study, we examined the effects of acute MAP administration on
      striatal extracellular levels of dopamine (DA) and its metabolites in groups of
      rats on postnatal days (PNDs) 14, 21, 28, and 56. A single injection of 4 mg/kg
      MAP (IP) induced increase in extracellular DA and decrease in extracellular 3,4
      dihydroxyphenylacetic acid (DOPAC) in the striatal perfusates of rats on all PNDs
      examined. The magnitude of increase in DA concentrations at 20 min after the MAP
      injection was significantly smaller on PND 14 than PNDs 21, 28, and 56, whereas
      the magnitude of decrease in DOPAC concentrations after the MAP injection was
      significantly smaller on PND 14 than PNDs 21, 28, and 56. After the MAP
      injection, homovanillic acid levels decreased on PNDs 21, 28, and 56, but
      increased on PND 14. These results suggest that rats on PND 14 differ from those
      thereafter in MAP-induced DA release and changes in its metabolites, and that
      such developmental effect on MAP-induced DA release may be involved in the
      ontogeny of MAP-induced behavioral sensitization.

PMID- 8866958
TI  - Benzodiazepine receptors increase induced by stress and maze-learning performance
      in chick forebrain.
AB  - Two-day-old chicks were selected on their second escape performance in a one
      trial, maze-learning task, and termed high-performance (H-P), moderate
      performance (M-P), and low-performance (L-P) chicks. The learning degree was
      expressed by the escape time improvement being respectively the 64, 46, and 24%.
      Then, the three selected groups were maintained to reach 15 days of age and then
      submitted to acute swimming stress, and [3H]flunitrazepam and [3H]Ro 5-4864
      receptor bindings were performed on synaptosomal/mitochondrial membranes from
      forebrain. The receptor number for both radioligands in stressed high-performance
      chicks was significantly higher than in stressed low-performance chicks. The
      results suggest that higher performance chicks were more susceptible than lower
      performance chicks to acute stress associated to increase of both central and
      peripheral type benzodiazepine receptors, probably due to differences in the
      degree of endogenous emotionality.

PMID- 8866960
TI  - Differential tolerance to the effects of chlordiazepoxide on unpunished and
      punished operant responding following chronic treatment.
AB  - Differential development of tolerance to the effects of benzodiazepines (BZs) is
      a common clinical phenomenon. To examine whether the development of tolerance to
      the response-suppressant and antipunishment effects of BZs were differentially
      regulated in animals, male Sprague-Dawley rats were treated chronically with
      either the BZ receptor agonist chlordiazepoxide (CDP, 25 mg/kg, IP, b.i.d.) or
      saline for 15 weeks and examined under a multiple schedule of operant behavior.
      Chronic administration of CDP produced tolerance to its suppressive effects on
      unpunished responding (RI 80 s) but no tolerance to its enhancing effects on
      punished responding. This conclusion is supported by three observations. First,
      repeated priming with CDP produced tolerance to its response-suppressive effects
      in the RI 80-s schedule and revealed increases in punished responding. Second,
      baseline levels for punished responding remained elevated over the 15-week
      treatment period. Third, tolerance developed to the response-suppressant effects
      of CDP under the RI 80-s schedule, as indicated by a sixfold shift to the right
      in the dose-response curves for rats treated chronically with CDP when compared
      to saline-treated controls. However, tolerance did not develop to the
      antipunishment effects of CDP, as indicated by no differences in the dose
      response curves for punished responding. Discontinuation of chronic treatment
      disrupted unpunished responding only on the first day, and reversed the increase
      in punished responding. Taken together, these results indicate that differential
      regulation occurs for the development of tolerance to the response-suppressant
      and antipunishment effects of BZs.

PMID- 8866959
TI  - Genetic differences in tolerance and sensitization to the sedative/hypnotic
      effects of alcohol.
AB  - Initial sensitivity to alcohol and the development of alcohol tolerance were
      examined in rats of the selectively bred alcohol-preferring (P) and 
      nonpreferring (NP) lines. All rats received two alcohol injections (3.0 g/kg
      b.wt., IP) separated by either 1 or 2 days. P rats were less sensitive to the
      behaviorally impairing effects of alcohol than were NP rats, as evidenced by a
      longer latency to lose righting reflex (RR) and a shorter time to recover RR
      following an initial alcohol injection. When 1 day separated the two alcohol
      injections, P rats recovered the RR more rapidly following a second injection
      compared to the first, indicating that the P rats developed tolerance to the
      sedative/hypnotic effects of alcohol. In contrast, the NP rats recovered the RR
      more slowly following the second injection compared to the first, indicating that
      the NP rats developed sensitization to alcohol. Tolerance in the P line and
      sensitization in the NP line disappeared when 2 days separated the two alcohol
      injections. Line differences in initial sensitivity and tolerance/sensitization
      to the behaviorally impairing effects of alcohol may contribute to the
      differences in alcohol consumption observed in the P and NP lines.

PMID- 8866961
TI  - Excessive stimulation of serotonin2 (5-HT2) receptors during late development of
      chicken embryos causes decreased embryonic motility, interferes with hatching,
      and induces herniated umbilici.
AB  - The existence and functional significance of 5-HT2 receptors in chicken embryos
      was studied by injecting the selective agonist dimethoxyiodophenylaminopropane
      (DOI), alone or in conjunction with the selective 5-HT2 antagonist ritanserin
      (RIT), into domestic chicken eggs with embryos of varying ages. DOI caused dose
      dependent reductions in hatchability and herniated umbilici in hatchlings. These
      effects were observed after injection early, mid, or late during embryonic
      development, with evidence of the toxic effects of DOI being greater in older
      embryos, probably due to 5-HT2 receptor activation late in development, even
      after injecting DOI as early as on day 3 of embryogenesis. This is based upon the
      fact that embryos in eggs injected with DOI early continued to develop apparently
      normally, failing to hatch, often after pipping their shells. Additionally, those
      that hatched often did so with herniated umbilici, as did late-exposed embryos,
      indicating that DOI's effects upon this organ were most likely mediated during
      the prehatching period (i.e., days 18-20). The agonist's selectivity was
      confirmed by the capacity of RIT to dose dependently block both of these toxic
      effects of DOI. Reduced embryonic motility monitored on day 19, after injection
      of DOI on the evening of day 18, suggests that excessive activation of 5-HT2
      receptors late during development of this species interferes with some normal
      embryonic behaviors and physiological changes necessary for inducing and/or
      maintaining the hatching process.

PMID- 8866962
TI  - Intraseptal microinjection of beta-funaltrexamine blocked a microwave-induced
      decrease of hippocampal cholinergic activity in the rat.
AB  - Acute (45 min) exposure to pulsed (2 microseconds pulse width, 500 pulses per
      second) 2450-MHz microwaves at a power density of 1 mW/cm2 (whole body specific
      absorption rate 0.6 W/kg) microwaves caused a decrease in cholinergic activity in
      the hippocampus of the rat as measured by the sodium-dependent high-affinity
      choline uptake. Microinjection of beta-funaltrexamine (1 microgram) into the
      septum before microwave exposure blocked this effect. These data indicate that mu
      opioid receptors in the septum mediate a microwave-induced decrease in
      cholinergic activity in the hippocampus and support our hypothesis that
      microwaves at a whole body SAR of 0.6 W/kg can activate endogenous opioids in the
      brain.

PMID- 8866963
TI  - Prenatal exposure to cocaine disrupts discrimination learning in adult rabbits.
AB  - Previous studies had shown that intrauterine exposure to cocaine produces an
      increase in the number of immunoreactive GABA neurons and abnormal dendritic
      structure of pyramidal cells in the anterior cingulate cortex, a brain region
      known to be involved in attentional processes and discrimination learning.
      Because structural abnormalities might be expected to produce related functional
      deficits, we examined whether intrauterine exposure to cocaine would affect
      discrimination learning in adult rabbits. We previously reported that cocaine
      progeny undergoing concurrent acquisition to visual and auditory CSs show a
      normal rate of learning to a light CS and an accelerated rate of learning to a
      tone. Here, we report that adult, Dutch-belted rabbits exposed to cocaine in
      utero showed impaired discrimination learning when responding to a positive
      visual cue but not when responding to a positive auditory cue. The nature of the
      deficit consisted of an impaired ability to acquire learned responses to the
      visual CS+ rather than in an impaired ability to withhold responses to the
      auditory CS-. Given that auditory stimuli tend to be more salient than visual
      stimuli in the normal rabbit, the preceding pattern of results suggests that
      intrauterine cocaine exposure affected the ability to preferentially attend to
      less salient but relevant stimuli and to ignore more salient, irrelevant stimuli.
      More importantly, these results indicate that prenatal exposure to cocaine
      produces neurobehavioral abnormalities which persist into adult life.

PMID- 8866964
TI  - Acute sensitivity vs. context-specific sensitization to cocaine as a function of
      genotype.
AB  - Individual variability in the acute and chronic effects of psychomotor stimulants
      is due, in part, to genetic factors. The purpose of this series of studies was to
      utilize a behavioral model of sensitization, namely increased locomotor activity,
      to assess individual variability in sensitization to the chronic effects of
      cocaine and its relationship to the acute stimulant effects of cocaine. Because
      the degree of sensitization is proportional to the training dose, genetic
      differences in acute sensitivity to cocaine were assessed and incorporated into
      the sensitization paradigm. Acute sensitivity and context-dependent sensitization
      were determined in six inbred mouse strains. Large quantitative and qualitative
      differences were found in the acute potency and efficacy of cocaine to stimulate
      locomotor activity. The ED50 was higher in the strains in which cocaine was most
      efficacious. Context-specific sensitization was determined via chronic
      administration of equiactive doses of cocaine (ED50) specifically paired with the
      test apparatus or with the home colony. Sensitization was time, environment, and
      genotype dependent. The differences in the number of trials required to show
      sensitization were unrelated to the acute locomotor stimulant effects of cocaine.
      These findings suggest that acute cocaine-induced locomotor activity and context
      specific sensitization reflect different pharmacological properties of cocaine.

PMID- 8866965
TI  - Passive avoidance learning in the day-old chick is modulated by GABAergic agents.
AB  - Injection of drugs directly into the intermediate medial hyperstriatum ventrale
      (IMHV) of day-old chicks, prior to training on a chrome bead dipped in either the
      strong aversant methyl anthranilate (MeA), or the weak aversant quinine, allows
      investigation of the effects of potential amnestic and memory-enhancing agents on
      retention of a passive avoidance task. Chicks were injected into the left and
      right IMHV, with either saline or muscimol (GABA agonist), 30 minutes before
      training on an MeA-coated bead. On test, either 10 min, 30 min or 24 h after
      training, birds were presented with a dry chrome bead. Normally, trained birds
      will avoid the test bead; however, significantly more muscimol-injected birds
      pecked the dry bead than did saline-injected chicks, indicating amnesia in the
      muscimol-injected birds. In chicks injected bilaterally into the IMHV with
      bicuculline, a GABAA antagonist, 30 minutes prior to training on a quinine-coated
      bead, avoidance scores were significantly improved on testing at 24 h compared
      with saline-injected control chicks, indicating enhanced retention in bicuculline
      treated birds. These results suggest a role for the GABAergic system in the
      acquisition and retention of passive avoidance learning in the day-old chick.

PMID- 8866966
TI  - Effects of nicotine withdrawal on central dopaminergic systems.
AB  - The behavioral and neurochemical manifestations in rats 24 h following the
      cessation of 14-day nicotine administration were investigated. Animals were
      implanted subcutaneously with osmotic minipumps which continuously released
      either saline or nicotine (1.5 mg/kg/day or 3.0 mg/kg/day) for 14 days. After the
      animals were withdrawn from nicotine for 24 h, we observed a significant decrease
      of locomotor activities and a reduction of dopamine contents in the striatum and
      nucleus accumbens. Nicotine withdrawal did not affect the body weight, food, or
      water consumption, and no deficit in the acquisition of a conditioned avoidance
      task was found in these animals. In addition, nicotine withdrawal did not alter
      the density or the binding affinity (Kd) of ligands to D1 and D2 receptors in the
      striatum. Although nicotine withdrawal did not alter the density or binding
      affinity of ligands to D1 receptors in the nucleus accumbens, the maximum number
      of D2 receptor sites were reduced by nicotine treatment. These results offer
      possible neurochemical mechanisms for changes of locomotor activity which
      occurred in rats during nicotine abstinence.

PMID- 8866967
TI  - Responses to novelty stress in female F344 rats: effects of age and d
      fenfluramine treatment.
AB  - To elucidate some of the mechanisms underlying the neuroendocrine and
      neurochemical changes associated with age in female rats, we administered the
      serotonin (5-HT) releaser and reuptake inhibitor, d-fenfluramine (d-FEN; 0.0 or
      0.6 mg/kg/day, PO) for 30-38 days to young (4 month) and old (21 month) F-344
      female rats. Animals were placed into a novel open field (OF) for 20 min before
      sacrifice. Control animals were sacrificed immediately upon removal from their
      home cage (HC). Old rats exhibited significantly (p < 0.05) less exploratory
      behavior and a smaller CORT response to OF than young animals. d-FEN treatment
      had no effect on plasma ACTH and CORT levels or exploratory behavior. The old HC
      rats had significantly (p < 0.05) higher plasma levels of prolactin (PRL) than
      the young HC rats. A stress induced increase in PRL secretion was observed in the
      old rats only, which was attenuated by d-FEN treatment. In the OF groups, both
      the young and old rats showed elevated medial frontal cortex (MFC) dopamine
      turnover (DOPAC/DA ratio), but only the young rats exhibited an elevation in
      norepinephrine (NE) turnover (MHPG/NE ratio). d-FEN treatment blocked the stress
      induced increase in NE turnover in the young rats and the increase in DA turnover
      in the old rats. These data suggest that 5-HT activity could be involved in the
      age-related changes in the MFC catecholamine and PRL responses to stress in
      female rats.

PMID- 8866968
TI  - Effect of midazolam with and without flumazenil on conditioned hypoalgesia.
AB  - The hot plate paradigm for pain threshold was used in two experiments to
      investigate the effects of the benzodiazepine midazolam and the benzodiazepine
      antagonist flumazenil on the acquisition of conditioned hypoalgesia. In
      Experiment 1, an infusion of midazolam (10 micrograms) into the nucleus
      accumbens, but not into the striatum or intermediate reticular zone, resulted in
      a complete blocking of the acquisition of conditioned hypoalgesia. Two possible
      mechanisms underlying this disruption in learning are discussed. Experiment 2
      revealed that systemically administered flumazenil (10 mg/kg) was capable of
      blocking the effect of midazolam observed in Experiment 1 only when administered
      in such a manner as to prevent any activity of midazolam at benzodiazepine
      receptors. These results suggest that the effect of midazolam observed in
      Experiment 1 was mediated by a relatively short action at benzodiazepine
      receptors.

PMID- 8866969
TI  - Aversive effects of the synthetic cannabinoid CP 55,940 in rats.
AB  - A series of experiments investigated the behavioral and hedonic effects of the
      synthetic cannabinoid CP 55,940 in male Wistar rats. CP 55,940 had a biphasic
      effect on locomotor activity, with a 10 micrograms/kg dose causing locomotor
      stimulation and a 100 micrograms/kg dose causing profound hypoactivity. CP 55,940
      (100 micrograms/kg) also caused a marked hypothermia for at least 3 h following
      administration, while lower doses (2.5 and 10 micrograms/kg) had no effect. CP
      55,940 (100 micrograms/kg) had anorexic and hyperdipsic effects for up to 24 h
      following administration and caused significant reductions in body weight. CP
      55,940 (100 micrograms/kg) also caused significant avoidance to a flavoured fluid
      (saccharin) with which it was paired. In the conditioned place preference
      paradigm both the 10 micrograms/kg and 100 micrograms/kg doses of CP 55,940
      produced significant place avoidance. It is concluded that CP 55,940 is aversive
      to rats. The possible mechanisms underlying this aversion are discussed.

PMID- 8866970
TI  - 3-O-acetylmorphine-6-O-sulfate: a potent, centrally acting morphine derivative.
AB  - In view of the potent analgesia exhibited by the apparent structurally dissimilar
      morphine-6-O-glucuronide (M6G) and morphine-6-O-sulfate (M6S) conjugates of
      morphine, we have examined the effect of structural modification of M6S on
      analgesic activity, using the tail-flick test. Changes in the M6S structure were
      made that would affect the lipophilicity and polarity of the molecule.
      Subcutaneous (sc) and intracerebroventricular (ICV) administration of equimolar
      doses of morphine, M6S, 3-O-acetylmorphine-6-O-sulfate (M3A6S), 3-O
      benzoylmorphine-6-O-sulfate (M3B6S), and 3-O-acetyl-N-methylmorphinium-6-O
      sulfate (MM3A6S) were employed. M6S and M3A6S exhibited a longer duration of
      action and greater activity compared to morphine after SC and ICV administration.
      However, M3B6S and MM3A6S in doses equimolar to that of morphine were found to be
      inactive after both SC and ICV administration. In addition, M3A6S showed the
      highest potency in inhibiting electrically stimulated guinea pig ileum followed
      by M6S and M3B6S. Moreover, both M6S and M3A6S displayed a greater affinity than
      that of morphine to mu and kappa 3 receptor sites in guinea pig brain homogenate.
      In contrast, the nonanalgesic compounds M3B6S and MM3A6S showed weak receptor
      binding ability compared to morphine. These results indicate that lipophilicity
      alone is not a determinant of analgesic activity in these novel morphine
      derivatives. These modified effects of morphine by the conjugations at the 3- and
      6-position, appear to be due to their altered interactions with opioid receptors.

PMID- 8866971
TI  - Distinct effects of N omega-nitro-L-arginine on seizures induced by several drugs
      in mice.
AB  - A potent nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (L-NA),
      suppressed tonic seizure elicited by pentylenetetrazol (PTZ; 100 mg/kg, SC) in a
      dose-related manner (25 to 100 mg/kg, IP), but had no effect on clonic seizure.
      The effect was most potent at 1 h after the administration of L-NA. L-NA (100
      mg/kg, IP) suppressed clonic seizure as well as tonic seizure in bicuculline
      treated (3.0 or 4.5 mg/kg, SC) mice. However, it did not affect seizures elicited
      by picrotoxin (2.0 to 6.0 mg/kg, SC). On the other hand, N-methyl-DL-aspartate
      (NMDLA; 300 mg/kg or 350 mg/kg, IP) induced clonic seizure, but tonic seizure was
      not always noted. All mice with clonic and tonic seizures died, and some mice
      with clonic seizure died without accompanying tonic seizure. L-NA did not
      influence NMDLA-induced seizures, but it appeared to enhance NMDLA lethality,
      though without statistical significance. These findings suggest distinct roles of
      NO in seizures induced by different drugs in mice.

PMID- 8866972
TI  - Reduced evoked release of acetylcholine in the rodent hippocampus following
      traumatic brain injury.
AB  - The chronic effects of traumatic brain injury on acetylcholine release were
      evaluated by using in vivo microdialysis. Acetylcholine release was measured in
      the hippocampus of anesthetized rats 2 weeks after lateral controlled cortical
      impact (n = 10) or sham surgery (n = 10). Prior to microdialysis, behavioral
      assessments of motor and spatial memory were performed. Cortical impact (6
      meter/s, 2 mm deformation) produced beam balance deficits that persisted for 1
      day and beam walking deficits that persisted for 3 days after injury. In
      addition, spatial memory, as measured by swim latencies in a Morris water maze,
      was compromised between 10-14 days after injury. Immediately following behavioral
      testing, the animals were anesthetized with halothane, and a microdialysis probe
      was placed into the dorsal hippocampus. After a 160 min equilibration period,
      extracellular levels of acetylcholine were measured prior to and after an
      intraperitoneal administration of scopolamine (1 mg/kg), which evokes
      acetylcholine release by blocking autoreceptors. Prior to scopolamine
      administration, there were no differences in extracellular levels of
      acetylcholine between injured and sham animals. However, there was a significant
      reduction of hippocampal acetylcholine release evoked by scopolamine in injured
      animals as compared to sham controls. In separate control groups, saline
      administration alone did not change hippocampal acetylcholine release in injured
      (n = 5) or sham (n = 5) animals. This study represents the first application of
      in vivo microdialysis to evaluate chronic neurotransmission deficits following
      TBI. The present study demonstrates that a magnitude of traumatic brain injury
      (TBI) sufficient to produce spatial memory deficits can result in a reduction in
      scopolamine-evoked release of acetylcholine within the hippocampus. The data
      further suggest that presynaptic mechanisms mediating release of acetylcholine
      could play a significant role in cholinergic neurotransmission deficits following
      TBI.

PMID- 8866974
TI  - Characterization of the conditioned taste aversion produced by 7-OH-DPAT in rats.
AB  - Using the conditioned taste aversion preparation, we described the dose-effect
      curve for the reputed dopamine D3 agonist (+/-)7-OH-DPAT (0, 0.001, 0.01, 0.1,
      1.0, or 10 mg/kg). Rats received a 0.1% saccharin taste paired on repeated
      occasions with one of the 7-OH-DPAT doses. The 0.1, 1.0, and 10.0 mg/kg doses of
      7-OH-DPAT produced a significant conditioned saccharin aversion. This aversion
      was evident regardless of whether saccharin intake of 7-OH-DPAT-treated rats was
      compared to their own water consumption or to saccharin intake by saline-treated
      rats.

PMID- 8866973
TI  - Effect of central acute administration of cadmium on drinking behavior.
AB  - The effect of acute third ventricle cadmium administration on the drinking
      behavior of adult male rats under different situations was studied. Injections of
      cadmium chloride (0.07, 0.7,and 7.0 ng/rat) significantly attenuated water intake
      in dehydrated rats. Drinking behavior induced by acute intracerebroventricular
      injections of carbachol (2 micrograms/rat) or angiotensin II (5 ng/rat) was also
      inhibited by central cadmium injections. Cadmium-induced blockade in water intake
      in dehydrated animals was reverted by the previous administration of a 5-HT2
      antagonist (RP62203) in different doses (5 and 10 micrograms/rat). The data
      clearly reveal that cadmium elicits very fast actions on the central nervous
      system. It is suggested that cadmium-induced attenuation of water intake may rely
      on at least three different mechanisms: impairment of cholinergic and
      angiotensinergic systems in the brain and stimulation of a central serotonergic
      drive acting on 5-HT2 receptors. The study of cadmium neurotoxicity by
      observation of drinking behavior, a behavioral parameter easy to be recorded and
      measured, is proposed.

PMID- 8866975
TI  - Acute behavioral effects of MK-801 in the mouse.
AB  - The acute effects of 0.05 mg/kg MK-801 on spatial learning and memory in male
      mice were studied using a modified hole board food search task. Dose-response
      sensorimotor and activity tests suggested that this dose of MK-801 did not induce
      significant nonassociative effects. Mice were trained on the hole board using a
      massed trials protocol to learn the location of a hole baited with a food reward
      among four corner holes. Retention was tested 24 h later. Mice were split into
      two groups matched according to acquisition scores. The following week, mice
      injected with 0.05 mg/kg MK-801 30 min before being trained to a different baited
      hole were significantly impaired in acquiring a new baited hole location compared
      to saline-treated mice, although retention performance was unaffected. The same
      result was found in another experiment in which treatments were crossed over, and
      a different version of the task was used. However, in another experiment, 0.05
      mg/kg MK-801 did not impair performance when the hole board task was well
      learned.

PMID- 8866976
TI  - Acute and chronic arecoline: effects on a scopolamine-induced deficit in complex
      maze learning.
AB  - These studies tested the effect of arecoline, a nonselective muscarinic agonist,
      administered either acutely or by chronic peripheral infusion via osmotic
      minipumps, on a scopolamine-induced deficit in a Stone (14 unit) T-maze task in
      rats. Scopolamine alone (0.125-1.0 mg/kg, IP) dose-dependently impaired maze
      acquisition, increasing maze run-times and to a lesser extent, the number of
      errors committed. Neither acute administration of arecoline (5.0 and 10.0 mg/kg,
      IP), when tested against a deficit induced by scopolamine (0.25 mg/kg, IP), nor
      chronic arecoline administration (30 and 50 mg/kg per 24 h), when tested against
      a deficit induced by scopolamine (0.5 mg/kg), were able to ameliorate the
      decrements in maze performance. In fact, the higher dose of arecoline (50 mg/kg
      per 24 h) infused over 10 days potentiated the scopolamine-induced deficit, with
      respect to latency. These data indicate that dose selection is of great
      importance when employing arecoline in tests of learning and memory and that the
      influence of the method of administration of arecoline on the behavioural outcome
      warrants further study.

PMID- 8866978
TI  - Morphine enhancement of sucrose palatability: analysis by the taste reactivity
      test.
AB  - The ability of morphine to modify sucrose palatability was assessed by the taste
      reactivity test. In Experiment 1, rats were injected with morphine (0.0, 0.5,
      2.0, and 10.0 mg/kg, subcutaneously), 30 min before receiving a 10-min intraoral
      infusion of 2% or 20% sucrose solution. A dose of 2.0 mg/kg morphine enhanced
      ingestive reactions elicited by both concentrations of sucrose solution. In
      Experiment 2, the interval between morphine pretreatment and the taste reactivity
      test was manipulated. Rats given 2.0 mg/kg morphine 30 or 120 min before testing
      displayed enhanced ingestive reactions elicited by 20% sucrose solution during
      the first 5 min of a 10-min test. The results support the hypothesis that
      morphine enhances the hedonic assessment of sucrose solution.

PMID- 8866977
TI  - Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat
      lines with differential sensitivity to ethanol.
AB  - Alcohol-nontolerant (ANT) rats, produced by selective breeding for high
      sensitivity to motor-impairing effects of ethanol, have a point mutation in the
      cerebellar gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit, which
      has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as
      well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and
      neurochemical methods to assess the significance of alpha 6- and non alpha 6
      containing GABAA receptor subtypes. Motor performance in a tilting plane test was
      largely unaffected by a type I benzodiazepine receptor-preferring agonist,
      zolpidem [1-10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists
      bretazenil and ZG-63 (both at 40 mg/kg, IP), and a novel broad-spectrum
      anticonvulsant loreclezole (40 mg/kg, IP) in both ANT and AT rats. In contrast,
      diazepam (10 mg/kg, IP) impaired performance of the ANT but not AT animals. These
      data, supported by results from brain regional autoradiography of [3H]Ro15-4513
      and membrane binding of [3H]ZG-63 and [35S]TBPS as influenced by these ligands,
      strongly suggest that only ligands with full agonist actions on mutant (ANT) but
      not wild-type (AT) alpha 6-containing GABAA receptors are able to produce motor
      impairment in the ANT rats.

PMID- 8866979
TI  - FS stress induces long-lasting memory facilitation: involvement of cholinergic
      pathways.
AB  - We tested in vivo the hypothesis that foot-shock (FS) stress-induced prolongation
      of latencies in the one-trial step-through passive avoidance learning task in
      mice occurred through a long-term facilitation process. Whereas behavioral
      responses in control mice lasted for 24 h, decreasing progressively in the
      subsequent days, FS-stress exposure for 15 min before training (pretraining),
      immediately after training (posttraining), or 15 min before the test (pretest)
      resulted in a profound and sustained enhancement of test latencies that lasted
      for at least 96 h. These facilitating effects disappeared when FS exposure was
      delivered with a 2- or 3-h difference with respect to the training trial.
      Scopolamine (Scop) (1 mg/kg, intraperitoneally) 30 min before the training
      session caused impairment of test latencies in control and pretest stressed
      animals, but failed to affect both pre- and posttraining FS stress-induced
      enhancement. Our working hypothesis is that FS stress may increase the levels of
      acetylcholine in the presynaptic terminal or the firing rate of cholinergic
      input. Animals pretreated with FS stress daily for 1 or 4 days followed by the
      acute schedule described above showed no enhancements of test latencies.
      Pretraining Scop impaired test latencies in pre- and posttraining and pretest
      stressed animals, suggesting that unpredictability is a critical factor in
      activating behavioral long-term facilitation.

PMID- 8866980
TI  - Anabolic-androgenic steroids and brain reward.
AB  - Anabolic-androgenic steroid (AAS) effects on brain reward were investigated in
      male rats with electrodes implanted in the lateral hypothalamus using the rate
      frequency curve shift paradigm of brain stimulation reward. In the first
      experiment, treatment for 2 weeks with the AAS methandrostenolone had no effect
      on either the reward or performance components of intracranial self-stimulation.
      In the second experiment, treatment for 15 weeks with an AAS "cocktail"
      consisting of testosterone cypionate, nandrolone decanoate, and boldenone
      undecylenate did not alter brain reward but did produce a slight but significant
      change in bar press rate. In addition to the AAS treatment, animals in the second
      study were administered a single injection of d-amphetamine before and after 15
      weeks of AAS exposure. The rate-frequency curve shift observed in response to a
      systemic injection of amphetamine was significantly greater in animals after 15
      weeks of treatment with the AAS cocktail. Although AAS do not appear to alter the
      rewarding properties of brain stimulation, AAS may influence the sensitivity of
      brain reward systems.

PMID- 8866981
TI  - Systemic and local cocaine increase extracellular serotonin in the nucleus
      accumbens.
AB  - The effect of systemic or intra-accumbens injections of cocaine on serotonin (5
      HT) overflow was studied by nucleus accumbens microdialysis in freely moving
      rats. In Experiment 1, cocaine was injected intraperitoneally at 0, 10, 20, and
      30 mg/kg. In Experiment 2, cocaine (3.6, 7.2, and 14.4 mM), lidocaine (7.2 mM),
      or saline was infused through the probe by reverse microdialysis. Extracellular
      serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured by high
      pressure liquid chromatography and electrochemical detection. Systemic
      administration of cocaine induced a dose-related increase in 5-HT overflow and a
      decrease of 5-HIAA. Intra-accumbens cocaine infusion also caused a dose-related
      increase in 5-HT, but no effect on 5-HIAA. As a control for local anesthesia,
      equimolar lidocaine did not increase 5-HT. The difference between lidocaine and
      cocaine was not due to unequal diffusion out of the probe, because previous in
      vivo calibration of the probe showed that more lidocaine than cocaine diffused
      out of the probe when equimolar solutions were infused. These experiments suggest
      that systemic cocaine acts on the nucleus accumbens to increase synaptic 5-HT.

PMID- 8866983
TI  - Rotavirus an emerging enteropathogen of man and animals: an overview.
AB  - Rota Viral infection is recognised as a significant global public health concern
      causing large numbers of potentially preventable illnesses and deaths, especially
      among young ones of man and animals. The paper presents an overview of the
      epidemiology, control, treatment, virology, diagnosis and the zoonotic aspects of
      the problem. Problems for further research are identified.

PMID- 8866982
TI  - Barakol: a potential anxiolytic extracted from Cassia siamea.
AB  - The behavioural effects of an extract of Cassia siamea, a plant used in Thai
      traditional medicine, and barakol, its active chemical, were studied on an
      elevated plus-maze compared with diazepam. An aqueous extract of C. siamea (1, 6,
      and 12 g/kg body wt., orally) produced a small increase in the percentage of the
      open: total number of arm entries and time, time spent on the end of the open
      arms, total number of arm entries, and number of rears/min. Barakol [10 mg/kg,
      intraperitoneally (IP)] significantly increased all of these behavioural
      parameters in a manner similar to diazepam (1 mg/kg, IP, 30 or 60 min before
      testing), except that barakol and not diazepam increased both the number of rears
      and total arm entries. Barakol at 25 and 50 mg/kg increased the percentage of the
      open: total number of arm entries and time and number of rears. The results
      indicate that barakol has anxiolytic properties similar to diazepam but differs
      from diazepam in that it also increases exploratory and locomotor behaviour, as
      shown by the number of rears and total arm entries.

PMID- 8866984
TI  - Serodiagnosis of tuberculosis.
AB  - To overcome limitations of the conventional laboratory tests for the diagnosis of
      tuberculosis, attempts have been made in the past to develop a good
      serodiagnostic test. Until the availability of ELISA results obtained with
      various immunological techniques were of limited use. Even with ELISA, early
      attempts to estimate specific antimycobacterial antibodies in the serum were
      based on the use of crude mycobacterial antigens resulting in a very high false
      positivity. Better results were obtained with purified antigens. Various purified
      and semipurified antigens which when used in the ELISA test for estimating
      antibodies in the serum and other body fluids in cases of tuberculosis have given
      encouraging results. These include a glycolipid antigen from Myc. bovis BCG (ST =
      88%, SP = 96%), antigen '5' (ST = 72%, SP = 91%) and a 38 Kd protein antigen (ST
      = 83%). Estimation of various mycobacterial antigens in different clinical
      specimens has also been studied using ELISA technique. Encouraging results have
      been obtained with the detection of a 43 Kd antigen, Lipoarabinomannan antigen
      and antigen '5' in the serum, CSF and other body fluids of cases of tuberculosis
      (ST = 80-100%, SP = 93-100%). The serological tests by detecting specific
      mycobacterial antigens and antibodies can be of great help in diagnosing the
      smear negative tuberculosis as these are rapid, inexpensive and simple to
      perform.

PMID- 8866985
TI  - Community perception of mosquitos and mosquito control in some areas of urban
      Delhi and rural Alwar, Rajasthan.
AB  - There is little information regarding community perception of mosquitos and and
      their control in India. A qualitative study based on In depth discussions with
      the people in Urban Delhi, and rural Alwar was carried out in August-September,
      1995. In the Ghazipur and Munirka areas of Delhi, 63 respondent groups with 171
      head counts, and 59 respondent groups and 305 persons in Alwar were met.
      Community responses to uniform set of questions on mosquito types, seasonality,
      biting, breeding places, ongoing control activities, and methods of personal
      protection were recorded. Most people in the areas surveyed viewed mosquitos
      primarily as a biting nuisance, and secondarily as agents of disease and
      debilitators of health. In general the knowledge regarding mosquitos was
      deficient. An overwhelming tendency to attribute mosquitogenic conditions to the
      unsavoury features of one's physical environment was observed in both areas. The
      methods of personal protection and attitudes to organised control are discussed.

PMID- 8866986
TI  - Coxsackie B virus in the etiology of heart diseases in Delhi.
AB  - Coxsackie B group of viruses have been long considered as the precipitating
      factor in heart diseases. Their association with various heart diseases
      especially pericarditis, myocarditis and myopericarditis is known, but now their
      association is also known with cardiomyopathy and ischaemic heart diseases. A
      study was carried out on 87 patients suffering from various heart diseases and
      the role of Coxackie B virus infection was studied. The study included 25 control
      subjects. Thirty patients (34.5%) were found to be having high antibody titre for
      at least one of coxsackie B virus group with coxsackie B3 and B4 being the two
      commonest types. Serum IgM immunoglobulins were raised in acute infective
      disorders like pericarditis, myocarditis and myopericarditis but IgG, IgA and IgM
      levels were normal in ischaemic heart diseases and cardiomyopathy.

PMID- 8866987
TI  - An institutional outbreak of hepatitis E--reported first time from Calcutta city.
AB  - A sudden outbreak of hepatitis occurred in a micro-epidemic form, amongst the
      staff members of the School of Tropical Medicine, Calcutta, during May-June,
      1995. A total of 21 persons developed jaundice, out of whom 11 members who
      attended the Virology Department and were tested for detection of different
      serological markers of hepatitis by ELISA. All the sera (N = 11) showed evidence
      of non-A, non-B infection by process of exclusion and 9 of the above sera showed
      evidence of anti-HEV when tested specifically. This is the first documented
      outbreak of viral hepatitis in respect of Calcutta.

PMID- 8866988
TI  - Validity of a mother's history of measles in children: a review of Indian
      literature.
AB  - A review of the available information on the validity of a mother's history of
      measles in children and its importance in Indian context is presented. A history
      of measles was found to have a median sensitivity (SN) of about 60% (n = 6; range
      33-75) and a median specificity (SP) of about 95% (n = 5; range 79-100). A
      subclinical infection seems to be the most plausible explanation for the low SN.
      Two mechanisms for the development of subclinical infection have been suggested:
      (i) In infants, exposure to the virus in the households when maternal antibodies
      are just sufficient to prevent the disease but not the infection. (ii) In older
      children, exposure to a mild dose of virus outside the households. However, due
      to the misclassification of non measles cases as measles, the SN increases and SP
      decreases as the child grows older. The implications of low SN, high SP and
      varying predictive values of the mother's history of measles are discussed.

PMID- 8866989
TI  - Sero-positivity of domestic animals against Japanese encephalitis in Bareilly
      area, U.P.
AB  - A study on seroprevalence of Japanese Encephalitis (JE), West Nile (WN) and
      Dengue-2 (DN-2) was undertaken in and around Bareilly, Uttar Pradesh to explore
      the role of non-human hosts in the natural cycle of these infections. A total of
      1449 animal sera samples collected from 104 dogs, 170 pigs, 170 horses, 333
      buffaloes, 252 cattle, 168 sheep and 252 goats were screened for antibodies
      against JE, WN and DN-2 by Micro-haemagglutination inhibition (HI) test employing
      4 to 16 HA units of JE, WN and DN-2 antigens. The HI positivity against JE was
      found in dogs (55.77%) followed by pigs (40%), horses (37.65%), buffaloes
      (21.92%), goats (17.86%), sheep (2.38%) and cattle (1.98%). The seropositivity
      against WN was relatively lower with 24.04% in dogs, pigs (27.65%) horses
      (25.88%) buffaloes (13.81%), goats (6.75%), cattle (1.19%) and nil in sheep. The
      seropositivity against DN-2 was lowest among all the three infections with 15.88%
      in horses, in dogs (15.38), pigs (11.76%) buffaloes (7.81%) and 3.97% in goats.
      All the cattle and sheep sera gave negative results against DN-2 antigen. The
      study showed endemicity of the infections in this area.

PMID- 8866990
TI  - Susceptibility status of Phlebotomus argentipes to DDT, dieldrin and malathion in
      Hoogly, West Bengal.
AB  - Susceptibility tests were carried out with DDT (4%), dieldrin (0.4%) and
      malathion (5%) using the WHO test kits against Phlebotomus argentipes sandflies
      collected from Dankuni, situated in Hoogly district, 21 km from Calcutta, West
      Bengal. P. argentipes was found to be susceptible to all the three insecticides
      tested. LT 50 was calculated to be 10.6 minutes, 10.2 minutes and 2.8 minutes for
      DDT, dieldrin and malathion against the flies.

PMID- 8866991
TI  - Epidemiology of meningococcal carrier state amongst recruits of a military
      training centre.
AB  - An epidemiological study was carried out to determine meningococcal carrier state
      amongst recruits of a military training centre. 360 recruits with divergent
      socioeconomic, ethnic backgrounds were studied. Epidemiological factors such as
      age, religion, educational status, housing conditions, family structure were
      considered. The overall carrier rate was 11.94%. Carrier rate was higher amongst
      recruits from poor background and joint families. No association was found
      between carrier state and smoking as well as those suffering from upper
      respiratory tract infection. Carrier rate was aslo studied in relation to age,
      marital status, educational back ground and region.

PMID- 8866992
TI  - Preventing gastro-enteritis deaths: recommendations based on a 3 years study.
AB  - Based on epidemiological investigation of 75 gstro-enteritis deaths that occurred
      in 22 major hospitals of Delhi during 1990-92, this paper deals with the
      observations pertaining to the role of physicians and health infrastructure in
      the management of gastro-enteritis patients. Majority of the patients visited
      private practitioners/clinics in the first instance. Hospital stay in 44% of
      cases was 6 hours or more, by which time dehydration and/or electrolyte imbalance
      should have been corrected. Still, in 54.5 percent out of these, dehydration was
      the cause of death, while in 18.2 percent electrolyte imbalance co-existed.
      Record maintenance at various hospitals was far from satisfactory. The study,
      highlighting the need for proper rehydration and timely referral enlists
      recommendations that might help in preventing gastro-enteritis deaths.

PMID- 8866993
TI  - Malaria problem and its control in north eastern states of India.
AB  - There has been a substantial increase in the overall malaria incidence and
      incidence of Plasmodium falciparum in the north-eastern region of India. The main
      contributory factors for this are: (i) difficult terrain, (ii) 'Jhum'
      cultivation, (iii) presence of optimum climatic conditions for prolonged
      transmission, (iv) presence of highly efficient malaria vectors, (v)
      developmental projects attracting aggregation of labour, (vi) influx of
      population along the international borders and (vii) chloroquine resistant P.
      falciparum strains. To combat this situation new approaches like providing 100
      per cent Central assistance, intensifying training of personnel and DDT spray,
      opening Drug Distribution Centres and Fever Treatment Depots and making drugs
      available in the villages have been put into action. In this communication the
      overall malaria situation in the north-east India is discussed.

PMID- 8866994
TI  - Problems of population based epidemiological surveys.
AB  - The author had the opportunity to plan and carry out a community based
      epidemiological survey of Delhi urban population and rural areas of Gurgaon
      (Haryana) for estimation of prevalence rates and risk factors for the coronary
      heart disease and hypertension. Based on the experience of conducting this
      largest population based epidemiological study in India for coronary heart
      disease and hypertension, problems in conducting these studies were identified.
      These are discussed in this paper so that other workers may benefit from this
      experience.

PMID- 8866995
TI  - Hepatitis C infection as an occupational hazard for healthcare workers.

PMID- 8866996
TI  - Presbyopia.
AB  - The need for bifocals causes more angst, fear, depression, denial, searching for
      alternatives, and needless self-pity than any other benign intervention in all of
      medicine. To many, this is the first sign they are on the other side of the hill
      of life. I will try to explain, with a minimum of numbers and equations, what
      presbyopia is and how it is managed (and perhaps even cured in the near future)
      in an understandable way. I will also present a few clinical situations which the
      primary care physician often meets. I suspect many of you are already wearing
      bifocals or are delaying the acquisition of them.

PMID- 8866997
TI  - Refractive surgery.
AB  - In recent years, there has been increasing interest in refractive surgery among
      patients and physicians. Refractive surgery lessens or eliminates the need for
      contact lenses or glasses. The goal of refractive surgery is to allow an
      individual more independence from optical devices. Technologic innovations have
      improved the predictability and safety of surgical correction of refractive
      errors and actually revolutionized treatment.

PMID- 8866998
TI  - Amblyopia & strabismus.
AB  - Amblyopia and strabismus are the most common ocular conditions occurring during
      childhood. Amblyopia is the leading cause of vision loss in childhood. Strabismus
      is a significant cause of ocular morbidity leading to amblyopia and psychosocial
      distress in childhood and into adulthood.

PMID- 8866999
TI  - Ocular manifestations in Down syndrome.
AB  - Down syndrome patients have characteristic ocular findings and associated
      problems and should have periodic ophthalmologic examinations. The ocular
      abnormalities of Down syndrome are, for the most part, amenable to treatment and
      significant visual loss should rarely occur in these patients. Early recognition
      and treatment will minimize added problems of visual deprivation and permit the
      patient with Down syndrome to function at his or her highest level of potential.

PMID- 8867000
TI  - Ocular manifestations of child abuse.
AB  - Certain ophthalmic signs have great significance in the diagnosis of child abuse.
      As Eisenbrey has stated, "unexplained retinal hemorrhages in children under three
      without external evidence of head injury should be considered diagnostic of child
      abuse until proven otherwise." While no one single ocular manifestation is
      pathognomic of child abuse, ocular examination can provide significant and
      compelling information which can aid in its diagnosis.

PMID- 8867001
TI  - Sports-related eye injuries.

PMID- 8867002
TI  - Oculogenital syndromes.

PMID- 8867003
TI  - AIDS and the eye.
AB  - The AIDS pandemic has finally emerged from the big cities to the small towns of
      this country, as patients with this disease are returning home to spend their
      last months and days in the care of their families. No physician will be spared
      from caring for patients with AIDS. This multisystem disease crosses the
      boundaries of primary and specialty medicine, and with its various
      manifestations, presents to virtually all health care professionals. This
      infection has an enormous impact on our society: economically, socially, and
      medically. The seriousness of this condition is reflected in the medical school
      curriculum at the University of Pittsburgh. AIDS education begins the first day
      of the first year for our medical students.

PMID- 8867004
TI  - Optic neuritis.
AB  - Optic neuritis is an acute inflammation of the optic nerve. It is a common
      manifestation of multiple sclerosis; it may be the initial expression or occur
      later in the course of the disease. Approximately 15-20% of cases of definite
      multiple sclerosis present with optic neuritis; another 40% will suffer an attack
      at some point. When optic neuritis occurs without antecedent signs of multiple
      sclerosis, magnetic resonance imaging (MRI) of the brain frequently reveals
      characteristic signal abnormalities of white matter, and analysis of
      cerebrospinal fluid often shows oligoclonal bands. Optic neuritis has been
      considered a forme fruste of multiple sclerosis.

PMID- 8867005
TI  - Tearing: lacrimal obstructions.
AB  - Tearing disorders are relatively common. Comprehensive consideration of the
      entire tearing system can assist the diagnosis and treatment of tearing problems
      to improve, if not cure, the condition. The general symptom complaint of "tearing
      or a feeling of wetness/irritation" most commonly relates to a dry or irritated
      eye, which usually responds well to medical therapy or punctal occlusion. True
      tearing from a lacrimal obstruction, however, is usually treated surgically. With
      a thorough understanding of the anatomy and physiology most tearing problems can
      be systematically analyzed, diagnosed, and treated with a high degree of
      satisfaction to the patient and physician.

PMID- 8867007
TI  - A transient outward cationic current activated by Na+ influx into frog visual
      neurones in vitro.
AB  - Whole cell patch clamp recording from neurones of a slice preparation of the frog
      optic tectum showed that depolarizing step commands from -70 mV holding potential
      generated a fast inward current always followed by a fast outward current. The
      fast outward current was blocked by tetrodotoxin (TTX) or 4-aminopyridine (4-AP),
      or by replacing external Na+ with Li+. When the patch pipette contained Cs+
      instead of K+ the outward current was fully preserved, suggesting that the
      membrane channels responsible for this response were relatively non-selective in
      their permeability properties. This current (termed Icat) is a novel example of a
      non-specific cationic current dependent on influx of Na+ and presumably important
      to control the firing characteristics of these cells.

PMID- 8867006
TI  - Behavioral and neurochemical alterations induced by reversible conductive hearing
      loss in aged male rats.
AB  - Eighteen months old male rats of the Sprague-Dawley strain were subjected to a
      reversible conductive hearing loss (HL) or a sham operation. A series of
      behavioral tests performed 3 months after surgery, revealed a sustained deficit
      in learning and memory capacity and a marked depressive attitude of rats with HL.
      At this time, a group of these animals were allowed to recover from HL for 1
      month and were again tested behaviorally compared to those with persistent
      auditory deficit. A better performance at the active and passive avoidance tests
      and normal responsiveness to the despair test was found in animals with recovered
      hearing capacity as compared to those with persistent HL. A biochemical analysis
      revealed a decrease of dopamine and homovanillic acid content and of choline
      acetyltransferase and acetylcholinesterase activity in the striatum and
      hippocampus of animals with persistent HL as compared to those with recovered
      auditory deficit. These data suggest that persistent auditory deafferentation
      affects cognitive mechanism in old rats in a reversible manner.

PMID- 8867008
TI  - Dose-dependent delivery of colchicine to the rat hippocampus by microdialysis.
AB  - The time courses of the colchicine delivery and diffusion rate in the brain were
      studied by microdialysis in the rat. Microdialysis allowed the exposure of the
      brain tissue to colchicine to be regulated, unlike a bolus injection. Colchicine
      was infused directly into the dorsal hippocampus at 40 ng/ml and 40
      micrograms/ml, for 8 h. The amount of colchicine delivered to the brain and the
      diffusion rate from the probe were dose-dependent: colchicine diffusion into the
      brain was linear at 40 ng/ml but tended to plateau after 4 h at 40 micrograms/ml.
      The drug actually delivered with the higher dosage was only about 50% of that
      predicted from a constant diffusion. The total amount delivered at 40 ng/ml was
      3.73 +/- 0.14 ng and at 40 micrograms/ml, it was 2.06 +/- 0.20 micrograms. Thus
      tissues surrounding the infusion site were saturated at high concentration and no
      more colchicine was diffused. Postmortem measurements of colchicine concentration
      in the forebrain confirmed these findings. Hence, the way in which colchicine is
      delivered to the brain is a critical factor for induction of its neurotoxic
      effects. These data open the way to a research on the correlation between local
      brain concentrations of colchicine and neurodegenerescence.

PMID- 8867009
TI  - Localization of heme oxygenase in rat retina: effect of light adaptation.
AB  - Heme oxygenase-2 isozyme is the predominant form of heme oxygenase in rat brain
      by western blot analysis. Heme oxygenase-1 isozyme is not induced by light
      adaptation in rat retina by western blot analysis. Immunocytochemistry localizes
      heme oxygenase-2 in three areas of the retina: the retinal pigment epithelium,
      inner segment and external nuclear layers of the rat retina. Ganglion cells and
      cell bodies of the internal nuclear layer of the retina and Muller cells were
      largely unstained for heme oxygenase-2. The localization of heme oxygenase-2 in
      the retina implies that its function is not associated with phototransduction.
      Also, light adaptation does not appear to induce heme oxygenase-1, a measure of
      oxidative injury.

PMID- 8867010
TI  - New hair cells arise from supporting cell conversion in the acoustically damaged
      chick inner ear.
AB  - Supporting cell mitosis contributes significantly to hair cell regeneration in
      the acoustically damaged bird inner ear. Yet there may be another mechanism of
      hair cell replacement: supporting cell conversion. This study used cytosine
      arabinoside (Ara-C), an inhibitor of DNA synthesis, to better determine whether
      supporting cells could transdifferentiate into hair cells without cell division.
      Chicks received Ara-C injections after acoustic overstimulation. Scanning
      microscopic studies of the basilar papillae revealed several unpaired, immature
      hair cells. To ensure Ara-C's blockage of DNA synthesis, one group of birds
      received both Ara-C and bromodeoxyuridine (BrdU), while another group had BrdU
      only. Immunocytochemical analysis of Ara-C/BrdU and BrdU papillae indicated zero
      and 16 dividing cells, respectively. This difference confirmed that Ara-C blocked
      DNA synthesis, arresting supporting cell mitosis. These data strongly suggest
      that supporting cell can convert into hair cells.

PMID- 8867011
TI  - Anatomical evidence for a bi-neuronal pathway connecting the nucleus tractus
      solitarius to caudal ventrolateral medulla to rostral ventrolateral medulla in
      the rat.
AB  - Using tract tracing techniques and dual-color histochemistry, this study
      investigated connections between the nucleus tractus solitarius (NTS), caudal
      ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM) in the
      rat. The anterograde tracer biotinylated dextran amine (BDA) was deposited into
      the NTS. The retrograde tracer Fluoro-Gold was deposited into the RVLM. In the
      CVLM, Fluoro-Gold-labeled cells were found intermingled with anterogradely
      labeled fibers coursing from the NTS. BDA-labeled axons, varicosities, and
      boutons were observed in close apposition to retrogradely labeled neurons in the
      CVLM. These data provide anatomical evidence for a bi-neuronal pathway from NTS
      to CVLM to RVLM; and support the hypothesis that these connections may comprise
      the medullary baroreceptor reflex pathway.

PMID- 8867012
TI  - Low Mg2+ induced epileptiform activity in the subiculum before and after
      disconnection from rat hippocampal and entorhinal cortex slices.
AB  - The subiculum is an area within the hippocampal complex which participates
      strongly in ictaform activity generated in the entorhinal cortex (EC). To study
      the properties of epileptiform activity with intra- and extracellular recording
      techniques in the subiculum, combined slices containing the EC, subiculum and
      hippocampus were prepared with and without surgical disconnection of the
      subiculum from the EC and area CA1. For induction of epileptiform activity
      extracellular magnesium was lowered. After acute disconnection of the subiculum
      from the cornu ammonis and the EC, seizure like events similar to those in the
      more intact preparation did develop. These were characterized by slow negative
      field potential shifts and, in intracellular recordings by sustained
      depolarization shifts lasting for 10-43 s. This activity could develop into late
      recurrent discharges of 1-2 s. These data indicate that the subiculum may be an
      important zone for epileptogenesis in temporal lobe epilepsy.

PMID- 8867013
TI  - GABAB-activated gK+ in thalamic neurons in the lethargic (lh/lh) mouse model of
      generalized absence seizures.
AB  - Whole-cell voltage-clamp recordings were made from thalamic ventrobasal (VB)
      neurons of age-matched lethargic (lh/lh) and wildtype (+/+) mice. Hyperpolarizing
      voltage commands (40 mV) from a holding potential of -60 mV were delivered to the
      cell and the resulting K+ conductance (gK+) activated by the GABAB receptor
      agonist baclofen was measured and compared between the two groups. VB cells from
      +/+ and lh/lh displayed no significant differences in resting conductance (gIN)
      or gK+ activated by baclofen. In addition to this, isolated, evoked GABAB
      mediated currents were recorded in VB cells. There was no significant difference
      in peak amplitude or latency to peak noted between the two groups. These data
      suggest that postsynaptic GABAB receptor-mediated function is not altered in VB
      thalamic neurones in this model of absence seizures.

PMID- 8867014
TI  - Evidence for modulatory effects of substance P fragments (1-4) and (8-11) on
      endogenous dopamine outflow in rat striatal slices.
AB  - The effects of substance P-(1-4) and substance P-(8-11) on endogenous dopamine
      outflow in rat striatal slices were investigated. The dose-response curves (0.01
      nM to 1 microM) were bell-shaped for both peptides, with significant increases in
      dopamine outflow at 0.1 and 1 nM. Dopamine overflow elicited by 1 nM substance P
      (1-4) or substance P-(8-11) and 25 mM KCl was additive. Although substance P-(8
      11) contains a truncated tachykinin sequence, the tachykinin NK1 receptor
      antagonist WIN 51,708 (17 beta-hydroxy-17 alpha-ethynyl-5 alpha-androstano[3,2
      b]pyrimido[1,2- a]benzimidazole (2.5 nM) fully reversed its effect. The
      interaction between the antagonist and 1 nM substance P-(1-4) was statistically
      not significant. The data constitute the first evidence that the fragments
      substance P-(1-4) and substance P-(8-11) could exert central effects and suggest
      that they may play a role in neuromodulation in the basal ganglia.

PMID- 8867015
TI  - Afferent sources of substance P in the C1 area of the rat rostral ventrolateral
      medulla.
AB  - To examine the potential extrinsic sources of substance P (SP)-containing
      terminals in the C1 area of the RVL, immunoperoxidase localization of SP was
      combined with retrograde transport of wheat germ agglutinin-conjugated
      horseradish peroxidase (WGA-HRP). In all cases examined, several neurons
      containing SP and WGA-HRP were found in the nucleus raphe pallidus and a few dual
      labeled neurons were found in the nucleus of the solitary tract and the
      paraventricular nucleus of the hypothalamus. In some cases, one or two double
      labeled neurons were detected in the lateral hypothalamic area and nucleus raphe
      obscurus. The results demonstrate that although several brain structures
      contribute SP afferents to the RVL, the nucleus raphe pallidus is the major
      extrinsic source.

PMID- 8867016
TI  - Non-invasive functional mapping with multi-channel near infra-red spectroscopic
      topography in humans.
AB  - Near-infrared spectroscopy (NIRS) is a new technique for non-invasive monitoring
      of tissue oxygenation and its kinetics. Up to this date, it has been used solely
      in research for the global hemodynamic change of the brain and for rough regional
      activation after stimulating the brain physiologically. This paper describes
      functional brain mapping using multi channel (ten channel) NIRS by applying the
      motor stimulation in humans. Our results demonstrate that the regional
      hemodynamic change was detected in a small area around the motor cortex with a
      time resolution of 1-2 s. NIRS technique offers considerable potential for
      research and clinical applications with no invasion.

PMID- 8867017
TI  - Lipopolysaccharide-induced nitric oxide synthase activity in cultured cerebellar
      granule neurons.
AB  - We examined the inducible form of nitric oxide synthase (iNOS) activity in
      cerebellar primary cultures enriched with granule neurons. Treatment with
      lipopolysaccharide (LPS) for 24 h was performed in two different cultures in
      which the survival of neurons was controlled by the levels of extracellular K+.
      Treatment of the granule neurons with the contaminating non-neuronal cells (< 5%)
      in a high K+ (25 mM) -containing culture medium with LPS induced four-fold NOS
      activity compared to that of the control, and the induced NOS activity was
      calcium-independent. LPS did not induce the NOS activity at all in the
      contaminating non-neuronal cells alone which were obtained by eliminating all the
      granule neurons from the culture by lowering the K+ concentration (5 mM). We
      conclude that the LPS-activated granule neurons can express iNOS activity and
      that this induction is not attributable to the contaminating nonneuronal cells.

PMID- 8867018
TI  - Suppression by GABAB receptors of 4-aminopyridine-induced hyperactivity in guinea
      pig dentate neurons.
AB  - Double intracellular recording from granule cells and hilar neurons was performed
      in hippocampal slices to study the effect of gamma-aminobutyric acid (GABA)
      receptor antagonists on the activity induced by the convulsant 4-aminopyridine (4
      AP) in the dentate gyrus. 4-AP evoked GABA-mediated responses in granule cells
      and burst discharges in hilar neurons. In the presence of GABAB but not GABAA
      receptor antagonists, 4-AP evoked discharge activity in dentate granule cells.
      When both GABAA and GABAB receptors were blocked 4-AP induced synchronous
      'paroxysmal depolarizing shift'-like activity in granule cells and hilar neurons.
      Our data indicate that GABAB receptor-mediated mechanisms protect dentate cells
      against the convulsant effects of 4-AP.

PMID- 8867019
TI  - Selective opposite modulation of dentate granule cells excitability by mu and
      kappa opioids in rat hippocampal slices.
AB  - The effects of opioids having affinity for kappa (U50,488H and U54,494A) and mu
      receptors (DAMGO and methadone) were tested on the excitability of the dentate
      and CA1 neurons in rat hippocampal slices. Slice perfusion with 25 microM
      U50,488H or with 12 microM U54,494A produced within 60 min a significant (P <
      0.05) decrease in the amplitude of the primary dentate population spike (PS). A
      similar decrease occurred on the CA1 PS amplitude only at concentrations higher
      than 100 microM of U50,488H or 50 microM of U54,494A. Slice perfusion with 0.5
      microM DAMGO, or 100 microM methadone produced an increase in the amplitude of
      the primary dentate and CA1 PS and the appearance of secondary PSs. Slice
      perfusion with 12 microM U50,488H or with 25 microM of methadone significantly (P
      < 0.05) decreased or increased, respectively, the rate of appearance of the
      dentate posttetanic potentiation (PTP) and long-term potentiation (LTP) after a
      100 Hz tetanic stimulation of the perforant path. The same concentration of
      U50,488H or methadone did not affect the rate of appearance of the CA1 PTP and
      LTP after a 100 Hz tetanic stimulation of the Schaffer collaterals. The data,
      providing evidence for a selective opposite modulation by mu and kappa opioids on
      the basal and stimulated dentate neuronal excitability, indicate the dentate area
      as a target within the hippocampus for an opposite influence between mu and kappa
      opioids on neuronal excitability.

PMID- 8867020
TI  - Extracellular Ca2+ changes during transmitter application in the leech central
      nervous system.
AB  - Changes in extracellular Ca2+ concentration ([Ca2+]e) evoked by transmitters and
      transmitter agonists, respectively, and by elevation of bath K+ concentration
      were recorded in isolated segmental ganglia of the leech Hirudo medicinalis using
      Ca(2+)-selective microelectrodes. A 1-min bath application of kainate (10
      microM), glutamate (1 mM), aspartate (1 mM), or carbachol (200 microM) decreased
      [Ca2+]e by up to 1 mM, whereas the inhibitory transmitters gamma-amino butyric
      acid (GABA, 100 microM) and serotonin (5-HT, 100 microM) did not change [Ca2+]e.
      The amplitude of the kainate-induced changes in [Ca2+]e increased with repetitive
      applications, and changes were blocked by 6-cyano-7-dinitroquinozaline-2,3-dione
      (CNQX). Elevation of bath K+ concentration from 4 to 40 mM led to a Ni(2+)
      sensitive decrease in [Ca2+]e by 0.9 mM. Our results suggest that excitatory
      transmission in the leech central nervous system might be accompanied by
      substantial decreases in [Ca2+]e.

PMID- 8867021
TI  - Apolipoprotein E polymorphism in patients with different neurodegenerative
      disorders.
AB  - Apolipoprotein E (ApoE) is associated with Alzheimer's disease (AD)
      neurofibrillary tangles and beta-amyloid protein in senile plaques. There are
      three common alleles of ApoE, designated epsilon 2, epsilon 3 and epsilon 4. We
      studied Finnish patients with neurodegenerative disorders: AD, vascular dementia
      (VAD), Parkinson's disease (PD), PD+dementia (PDD), Lewy body variant of AD (LB),
      frontal dementia (FD), and Down's syndrome (DS), as well as control individuals
      (C). The ApoE genotypes and corresponding allele frequencies of 188 patients and
      60 controls were determined by digestion of ApoE polymerase chain reaction
      products with the restriction enzyme Hha I. The ApoE epsilon 4 allele frequency
      was 0.17 for C, 0.44 for AD, 0.35 for VAD, 0.10 for PD, 0.38 for PDD, 0.28 for
      LB, 0.39 for FD, and 0.17 for DS. We found significant differences in genotype
      frequency between AD/C, AD/PD and AD/DS. Our results suggest that, beside AD, an
      increased frequency of epsilon 4 may also be involved in other dementing
      neurological disorders.

PMID- 8867022
TI  - Intrinsic neuronal cell bodies in the rat ovary.
AB  - The present study describes ganglia and isolated neurones in the ovary of the
      Wistar rat, employing histological and histochemical techniques. Four kinds of
      ganglia in the postpubertal and young adult rat were identified: the mesovarial,
      hilar, medullary and cortical ganglia. Isolated neurones were also found, being
      dispersed along blood vessels in the ovary medulla and near the follicles. The
      soma diameters of these neuronal cells ranged from 25 to 50 microns. In the
      prepubertal rat, only the mesovarial and hilar ganglia were observed. They
      contained small neurones with soma diameters ranging from 10 to 15 microns. NADPH
      diaphorase activity was detected in some isolated neurones and in the cortical
      and hilar ganglia in all rats examined.

PMID- 8867023
TI  - Screening for amyloid beta precursor protein codon 665, 670/671 and 717 mutations
      in Finnish patients with Alzheimer's disease.
AB  - In this study, we screened for the amyloid beta precursor protein (APP) 665
      (glutamic acid to aspartic acid), 670/671 (lysine to asparagine and methionine to
      leucine) and 717 (valine to isoleucine) mutations in 34 persons affected with
      familial Alzheimer's disease (AD) and 139 with sporadic AD, originating from
      eastern Finland, using polymerase chain reaction amplification and restriction
      enzyme digestion. We did not find any of these mutations in the APP gene in our
      study. We conclude that these mutations in the APP gene may be a very rare cause
      of AD in Eastern Finland and thus most Finnish familial AD will likely be due to
      other gene defects.

PMID- 8867024
TI  - Frontal cortex ablation reversibly decreases striatal zif/268 and junB
      expression: temporal correspondence with sensory neglect and its spontaneous
      recovery.
AB  - This study's goal is to identify subcortical adaptations that may contribute to
      recovery of function following cortical injury. After unilateral aspiration of
      the medial agranular region of frontal cortex (AGm), rats demonstrate neglect of
      contralateral stimuli and recover within 3-4 weeks. Previous studies indicate
      that compensatory neural alterations involving dopamine (DA) occur following this
      cortical injury and that recovery from neglect produced by frontal injury is
      accompanied by normalization of glucose utilization within subcortical structures
      including the basal ganglia. The current study examined Zif and JunB, IEG protein
      products constitutively expressed in striatum, rendering it possible to
      investigate the effects of unilateral AGm ablation on striatal function during
      unstimulated as well as amphetamine-stimulated conditions. Five days after
      surgery, when contralateral neglect was still evident, the numbers of Zif-like or
      Jun-like immunoreactive (IR) nuclei in the ipsilateral striata of AGm-ablated
      rats were reduced. These lesion effects were similar for both constitutive and
      amphetamine-stimulated IEG expression and were restricted to the dorsolateral
      caudate-putamen, where excitatory input from AGm is most dense. In contrast, 3 or
      more weeks after AGm ablation, in rats demonstrating recovery, normal striatal
      Zif- and JunB-like immunoreactivity occurred. Thus, striatal zif/268 and junB
      expression is reduced 5 days after AGm injury in rats demonstrating neglect and
      normalized 3 or more weeks later in recovered rats. These findings indicate that
      adaptations involving the striatal medium spiny neuron, a site of convergence of
      cortical glutamatergic and nigral dopaminergic afferents, may contribute to
      behavioral recovery following neocortical injury.

PMID- 8867025
TI  - Differential effects of phencyclidine and methamphetamine on dopamine metabolism
      in rat frontal cortex and striatum as revealed by in vivo dialysis.
AB  - We have examined the effects of schizophrenomimetic drugs including phencyclidine
      (PCP) and methamphetamine (MAP) on cortical and striatal dopamine (DA) metabolism
      using an in vivo dialysis technique in the rat. An acute systemic injection of
      PCP (2.5-10 mg/kg, intraperitoneally (i.p.)) dramatically increased
      concentrations of DA, 3,4-dihydroxy-phenylacetic acid, and homovanillic acid in
      the dialysates from the medial frontal cortex in a dose-dependent fashion.
      However, PCP (2.5-10 mg/kg, i.p.) caused a much lower augmentation of
      extracellular DA release, with a significant decrease in dialysate DOPAC levels
      in the striatum. Moreover, continuous infusion of tetrodotoxin (TTX, 10(-5) M)
      into the prefrontal or striatal region through the microdialysis tube completely
      blocked the ability of PCP (10 mg/kg, i.p.) to alter the extracellular release of
      DA and its metabolites in the respective areas. In contrast, MAP (4.8 mg/kg,
      i.p.) elicited a marked and tetrodotoxin-resistant increase in DA levels with a
      significant loss of DOPAC contents in the extracellular space of both the frontal
      cortex and the striatum. The present results clearly demonstrate the differential
      effects of PCP on cortical and striatal DA transmission, suggesting that PCP may
      facilitate DA release in the medial frontal cortex by increasing impulse flow in
      the DA neurons projecting to the cortical area, whereas PCP-induced elevation of
      extracellular DA in the striatum may be caused mainly by reuptake inhibition of
      DA liberated by basal activity of the striatal DA neurons. The regional variation
      in PCP-induced DA release would be due to the combination of NMDA (N-methyl-D
      aspartate) receptor blocking and DA reuptake inhibition by the drug. The uniform
      and TTX-resistant nature of MAP-induced changes in brain DA metabolism may result
      from the direct actions of MAP at DA nerve terminals.

PMID- 8867026
TI  - Pyramidal neurons in rat prefrontal cortex show a complex synaptic response to
      single electrical stimulation of the locus coeruleus region: evidence for
      antidromic activation and GABAergic inhibition using in vivo intracellular
      recording and electron microscopy.
AB  - Cognition and acquisition of novel motor skills and responses to emotional
      stimuli are thought to involve complex networking between pyramidal and local
      GABAergic neurons in the prefrontal cortex. There is increasing evidence for the
      involvement of cortical norepinephrine (NE) deriving from the nucleus locus
      coeruleus (LC) in these processes, with possible reciprocal influence via
      descending projections from the prefrontal cortex to the region of the LC. We
      used in vivo intracellular recording in rat prefrontal cortex to determine the
      synaptic responses of individual neurons to single electrical stimulation of the
      mesencephalic region including the nucleus LC. The most common response consisted
      of a late-IPSP alone or preceded by an EPSP. The presence of an early-IPSP
      following the EPSP was sometimes detected. Analysis of the voltage dependence
      revealed that the late-IPSP and early-IPSP were putative K(+)- and Cl- dependent,
      respectively. Synaptic events occurred following short delays and were
      inconsistent with the previously reported time for electrical activation of
      unmyelinated LC fibers. Moreover, systemic injection of the adrenergic
      antagonists propranolol (beta receptors), or prazosin (alpha 1 receptors), did
      not block synaptic responses to stimulation of the LC region. Finally, certain
      neurons were antidromically activated following electrical stimulation of this
      region of the dorsal pontine tegmentum. Taken together, these results suggest
      that the complex synaptic events in pyramidal neurons of the prefrontal cortex
      that are elicited by single electrical stimulation of the LC area are mainly due
      to antidromic activation of cortical efferents. Further insight into the chemical
      circuitry underlying these complex synaptic responses was provided by electron
      microscopic immunocytochemical analysis of the relations between the
      physiologically characterized neurons and either 1) GABA or 2) dopamine-beta
      hydroxylase (DBH), a marker for noradrenergic terminals. GABA-immunoreactive
      terminals formed numerous direct symmetric synapses on somata and dendrites of
      pyramidal cells recorded and filled with lucifer yellow (LY). In contrast, in
      single sections, noradrenergic terminals immunoreactive for DBH rarely contacted
      LY-filled somata and dendrites. These results support the conclusion that IPSPs
      observed following single electrical stimulation of the LC region are mediated by
      GABA, with little involvement of NE. These IPSPs, arising from antidromic
      invasion of mPFC cells innervating the LC, may improve the signal-to-noise ratio
      and favor a better responsiveness of neighboring neurons to NE released in the
      mPFC.

PMID- 8867027
TI  - Facilitation of glutamate receptors reverses an age-associated memory impairment
      in rats.
AB  - The accuracy of memory for recent events is reported to decay between young
      adulthood and middle age in humans (Crook et al., 1990; Crook and West, 1990;
      Thomas et al., 1977) due to impairments in acquisition and/or retention (Craik,
      1977; Huppert and Kopelman, 1989). Effects of this kind are also found in
      comparisons of middle-aged (12-18 months) vs. young adult (3 months) rats in
      tests requiring retention of recently sampled spatial cues (Kadar et al., 1990a;
      Kadar et al., 1990b; Goudsmit et al., 1990; Weiss and Thompson, 1991). The causes
      of such changes in memory processing are unknown but might be expected to involve
      age-related losses in forebrain glutamate receptors (Bahr et al., 1992; Magnusson
      and Cotman, 1993; Wenk et al., 1991); these receptors mediate fast excitatory
      transmission in many brain regions and play an essential role in the production
      of long-term potentiation (LTP), a form of synaptic plasticity that has been
      implicated in memory encoding (Landfield and Lynch, 1977; Moore et al., 1993). In
      the present communication we report results indicating that a drug that enhances
      AMPA-type glutamate receptors acts centrally to selectively increase hippocampal
      spatial cell firing and improves both acquisition performance and memory
      retention in middle-aged rats to levels equivalent to those found in young adult
      animals.

PMID- 8867028
TI  - Differences in the subregional and cellular distribution of GABAA receptor
      binding in the hippocampal formation of schizophrenic brain.
AB  - Recent postmortem studies have reported a marked upregulation of GABAA receptor
      binding activity in the anterior cingulate and prefrontal cortices of
      schizophrenic subjects. Because the hippocampal formation is a key corticolimbic
      region that has also been implicated by both postmortem and brain imaging studies
      in the pathophysiology of this disorder, the current report has sought to
      determine whether alterations of GABAA receptor binding might also be detected in
      this region from 15 normal controls and 8 schizophrenic subjects. Using a low
      resolution autoradiographic approach, the results show a significant increase of
      specific GABAA receptor binding activity in the area dentata (granule cell
      layer), CA4, CA3 (str. oriens, str. pyramidale), subiculum, and presubiculum of
      the schizophrenic group. The magnitude of the increase was greatest in CA3 and
      lowest in the CA1 sector. When high resolution analyses were performed on
      emulsion-coverslip preparations, a modest increase of binding (43%, P = 0.05) was
      observed on pyramidal, but not non-pyramidal neurons in sector CA1. Rather
      unexpectedly, GABAA binding in sector CA3 was not significantly different on
      pyramidal cells, but was almost three-fold higher (P = 0.015) on non-pyramidal
      neurons of the schizophrenic group. There was no relationship of age or the
      postmortem interval to the parameters showing significant changes in the
      schizophrenic group. Moreover, patients both with and without neuroleptic
      exposure showed upregulation of GABAA receptor binding activity. Taking together
      the rather modest increase of binding activity in CA1 and the more marked
      upregulation in CA3, as well as the differential changes on pyramidal neurons of
      CA1 vs. non-pyramidal neurons in CA3, the findings reported here are consistent
      with the possibility that a disturbance of brain development could have occurred
      either perinatally or perhaps even well into the postnatal period, and have given
      rise to discreet subregional and cellular alterations of disinhibitory GABAergic
      modulation in sector CA3 of schizophrenics. Overall, the data reported here
      provide further evidence that alterations of GABAergic activity may occur in the
      hippocampal formation of schizophrenic patients.

PMID- 8867029
TI  - Activation of corticostriatal pathway leads to similar morphological changes
      observed following haloperidol treatment.
AB  - Treatment with haloperidol, a dopamine receptor D-2 antagonist, for one month
      resulted in an increase in the mean percentage of asymmetric synapses containing
      a discontinuous, or perforated, postsynaptic density (PSD) [Meshul et al. (1994)
      Brain Res., 648:181-195] and a change in the density of striatal glutamate
      immunoreactivity within those presynaptic terminals [Meshul and Tan (1994)
      Synapse, 18:205-217]. We speculated that this haloperidol-induced change in
      glutamate density might be due to an activation of the corticostriatal pathway.
      To determine if activation of this pathway leads to similar morphological changes
      previously described following haloperidol treatment, GABA (10(-5) M, 0.5
      microliters) was injected into the thalamic motor (VL/VM) nuclei daily for 3
      weeks. This treatment resulted in an increase in the mean percentage of striatal
      asymmetric synapses containing a perforated PSD and an increase in the density of
      glutamate immunoreactivity within nerve terminals of asymmetric synapses
      containing a perforated or non-perforated PSD. Subchronic injections of GABA into
      the thalamic somatosensory nuclei (VPM/VPL) had no effect on the mean percentage
      of synapses with perforated PSDs but resulted in a small, but significant,
      increase in density of glutamate immunoreactivity. Using in vivo microdialysis,
      an acute injection of GABA (10(-5) M, 15 microliters) into VL/VM resulted in a
      prolonged rise in the extracellular level of striatal glutamate. The increase in
      asymmetric synapses with perforated PSDs and in glutamate immunoreactivity within
      nerve terminals of the striatum following either subchronic haloperidol treatment
      or GABA injections into VL/VM suggest that an increase in glutamate release may
      be a common factor in these two experiments. It is possible that the
      extrapyramidal side effects associated with haloperidol treatment may be due, in
      part, to an increase in release of glutamate within the corticostriatal pathway.

PMID- 8867030
TI  - MK-801 (dizocilpine): synergist and conditioned stimulus in bromocriptine-induced
      psychomotor sensitization.
AB  - Intraperitoneal injections of the D2/D3 dopamine agonist bromocriptine (5.0
      mg/kg, IP) induced locomotion that became progressively stronger on successive
      days of testing. The sensitized response developed twice as rapidly when the non
      competitive NMDA antagonist MK-801 (0.25 mg/kg, IP) was given 30 min after
      bromocriptine (so that the peak effects of the two drugs overlapped). In a second
      group of animals, MK-801 was given 30 min prior to bromocriptine (the
      pretreatment regimen typical of studies where MK-801 is reported to block
      cocaine, amphetamine or morphine sensitization) and locomotion was monitored
      during the pretreatment period; in this case sensitization to the locomotor
      stimulating effects of MK-801 alone (in the pretreatment period) as well as
      sensitization to the locomotor-stimulating effects of the drug combination
      (following the second injection) were observed. No sensitization to the effects
      of MK-801 alone (pretreatment) were seen in animals that received saline rather
      than bromocriptine as their second injection in this experiment. Thus MK-801 does
      not block but rather enhances bromocriptine sensitization; it appears to do so by
      a synergism with the locomotor effects of bromocriptine and by becoming a
      conditioned stimulus for the sensitized response. These findings confirm the
      earlier report that NMDA receptor activation is not critical to bromocriptine
      induced sensitization, and they illustrate the importance of controls for
      conditioning and state-dependency phenomena in studies of drug interactions in
      psychomotor sensitization.

PMID- 8867031
TI  - Condition-independent sensitization of locomotor stimulation and mesocortical
      dopamine release following chronic nicotine treatment in the rat.
AB  - Chronic nicotine (NIC) pretreatment has been shown to enhance NIC-induced
      locomotor stimulation, an effect that seems critically dependent on activation of
      brain dopamine (DA) systems. In the present study the effects of chronic,
      intermittent NIC treatment were examined in the rat to establish whether such
      behavioral sensitization is associated with specific, regional changes in brain
      dopaminergic activity. Male rats received daily injections in their home cage
      with either saline (SAL) or NIC (0.5 mg/kg, s.c.) for 12 days. Twenty-four hours
      later, the locomotor activity of the animals subjected to NIC challenge as well
      as the functional responsiveness of the mesolimbocortical dopaminergic system
      were assessed. To this end, microdialysis experiments were performed in awake
      animals, measuring extracellular concentrations of DA and its metabolites in the
      prefrontal cortex (PFC) and the nucleus accumbens (NAC). Extracellular single
      cell recordings from DA neurons in the ventral tegmental area (VTA) were also
      performed in anesthetized animals. NIC (0.5 mg/kg, s.c.) increased all measured
      parameters of locomotor activity, with the exception of rearing, in SAL
      pretreated animals; these effects were substantially enhanced after pretreatment
      with NIC. Nicotine (0.5 mg/kg, s.c.) increased DA release in both the PFC and the
      NAC in SAL-treated animals. Nicotine pretreatment significantly enhanced this
      effect in the PFC, whereas it did not affect the response in the NAC. Low doses
      of intravenously administered NIC dose-dependently increased burst activity,
      starting at 12 micrograms/kg in the SAL pretreated animals and at 6 micrograms/kg
      in the NIC-pretreated animals, and also dose-dependently increased firing rate in
      SAL as well as NIC-pretreated animals, although starting at a higher dose level,
      i.e., 25 micrograms/kg. These results demonstrate that behavioral sensitization
      after chronic NIC treatment is accompanied by an enhanced dopamine release
      specifically within the PFC. This phenomenon may be highly significant for the
      dependence-producing effects of NIC, particularly in association with major
      psychiatric disorder, such as schizophrenia.

PMID- 8867032
TI  - Modulation of GABAergic transmission in the globus pallidus by the synthetic
      cannabinoid WIN 55,212-2.

PMID- 8867034
TI  - Current world literature.

PMID- 8867033
TI  - [11C]beta-CIT-FE, a radioligand for quantitation of the dopamine transporter in
      the living brain using positron emission tomography.
AB  - The cocaine analogue beta-CIT-FE (N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4
      iodophenyl)nortropane) was labeled with 11C for positron emission tomography
      (PET) studies of the dopamine transporter. After intravenous administration to a
      cynomolgus monkey, [11C]beta-CIT-FE accumulated in the striatum with a striatum
      to-cerebellum ratio of about 9 after 60 min. Pseudoequilibrium of specific
      [11C]beta-CIT-FE binding in the striatum was obtained within 30-50 min. The
      radioactivity ratios of the thalamus to the cerebellum and the neocortex to the
      cerebellum were about 2 and 1.5, respectively. In displacement and pretreatment
      experiments, radioactivity in the striatum but not in the cerebellum was reduced
      after injection of beta-CIT or the dopamine transporter inhibitor GBR 12909,
      indicating that striatal radioactivity following injection of [11C]beta-CIT-FE
      represents reversible binding to dopamine transporter sites. After displacement
      or pretreatment with cocaine there was a marked effect not only in the striatum
      but also in the thalamus and neocortex. [11C]beta-CIT-FE has potential as a
      useful PET radioligand for quantitation of the dopamine transporter in the
      primate brain in vivo.

PMID- 8867035
TI  - N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors mediate seizures and
      CA1 hippocampal damage induced by dendrotoxin-K in rats.
AB  - The epileptogenic and neurodegenerative effects of dendrotoxin K, from
      Dendroaspis polylepis, a specific blocker of a non-inactivating, voltage
      sensitive K+ channel, were studied after focal injection into one dorsal
      hippocampus in rats. Administration of 35 pmol dendrotoxin K elicited motor
      seizures and bilateral electrocortical discharges after a latent period (5.3 +/-
      2.1 min), in all of the treated animals (n = 6). At 24 h, histological
      examination of brain (n = 5) coronal sections (10 microns; n = 6 per brain)
      detected bilateral damage to the hippocampal formation which extended 300 microns
      rostral and caudal to the injection tract. Quantitation of the damage revealed
      significant bilateral neuronal cell loss in the CA1 and CA4 pyramidal cell layer
      relative to the corresponding brain regions of rats (n = 3) injected with bovine
      serum albumin (105 pmol), which per se was ineffective in all respects.
      Dendrotoxin K (35 pmol) also caused a significant loss of CA3 pyramidal neurons
      and dentate gyrus granule cells ipsilateral to the site of toxin injection. In
      one out of six rats, a lower dose (3.5 pmol) of dendrotoxin K produced convulsive
      behaviour and electrocortical seizures but after a longer latency and these were
      accompanied by significant neuronal loss in the CA1, CA3 and CA4 pyramidal cell
      layer ipsilateral to the injected side. The lowest dose (0.35 pmol; n = 6 rats)
      of dendrotoxin K used failed to induce seizures and did not cause hippocampal
      damage (n = 6 rats). Systemic (i.p.) treatment with dizocilpine maleate (3 mg/kg)
      or LY 274614 (5 mg/kg i.p.), two N-methyl-D-aspartate receptor antagonists (given
      15 min beforehand), prevented dendrotoxin K (35 pmol)-induced motor seizures and
      electrocortical epileptogenic discharges in 100% of the animals (n = 6 per group)
      treated. Similarly, these antagonists minimized the damage typically produced in
      the rat hippocampus, with no significant neuronal loss being observed. By
      contrast, NBQX (30 mg/kg, i.p. given 15 min previously), a non-N-methyl-D
      aspartate antagonist, failed to prevent seizures normally evoked by dendrotoxin K
      (35 pmol; n = 6 rats); also, this treatment was unable to abolish CA1 pyramidal
      cell loss but minimized the loss in hippocampal sectors distant to the site of
      dendrotoxin K injection. However, complete protection against motor and
      electrocortical seizures and hippocampal damage was afforded by GYKI 52466 (10
      mg/kg i.p.; n = 6 rats), a more effective non-N-methyl-D-aspartate receptor
      antagonist. These findings differ from the reported lack of protection by N
      methyl-D-aspartate and non-N-methyl-D-aspartate receptor antagonists to rats
      receiving intra-hippocampal injection of alpha-dendrotoxin; this difference may
      stem from the ability of alpha-dendrotoxin to block predominantly a slowly
      inactivating K+ current whereas dendrotoxin K inhibits a non inactivating
      variant. In conclusion, the present data on dendrotoxin K, together with the
      previously described pattern of neurotoxicity for alpha-dendrotoxin, show that
      these homologues act via different mechanisms and, thus, can be used effectively
      as complementary tools to study seizures and neuronal cell death.

PMID- 8867036
TI  - Veratridine-enhanced persistent sodium current induces bursting in CA1 pyramidal
      neurons.
AB  - The mechanism of veratridine-induced bursting activity was studied in rat
      hippocampal CA1 pyramidal neurons. Veratridine (0.1-0.3 microM) induces bursting
      in previously normal pyramidal neurons. The current-voltage curves of untreated
      neurons show a slight deviation from the linear Ohmic relation; this deviation is
      known as the "depolarizing rectification". Veratridine markedly accentuates the
      depolarizing rectification so that a zero slope or negative slope appears in the
      current-voltage curve of these neurons. Both the veratridine-induced bursting
      activity and negative slope resistance are blocked by small concentrations of
      tetrodotoxin or by raising the calcium concentration of the superfusion medium.
      Under single-electrode voltage clamping, a subthreshold persistent (slowly
      inactivating) sodium current, which can be recorded in untreated neurons, is
      found to be enhanced in the veratridine-treated neurons. This current is thought
      to be responsible for the slow depolarizing phase of bursting activity and the
      development of negative slope resistance in the current-voltage relationship. The
      present results demonstrate that veratridine enhances the slowly inactivating
      sodium current, leading to the development of negative slope resistance and
      induction of bursting in rat hippocampal CA1 pyramidal neurons.

PMID- 8867037
TI  - Distribution of substance P-immunoreactive neurons and fibers in the monkey
      hippocampal formation.
AB  - Substance P containing neurons was visualized by immunocytochemistry in the
      monkey hippocampus, subicular complex, and entorhinal cortex. Immunoreactive
      neurons were found solely in the hilar region of the dentate gyrus, and in strata
      oriens and pyramidale of Ammon's horn. In the subicular complex, immunoreactive
      neurons were located in those layers which were close to the alveus, whereas in
      the entorhinal cortex most of the substance P-positive neurons appeared in the
      second and third layers above the lamina dissecans. The majority of substance P
      containing neurons were large multipolar cells, but small bipolar and multipolar
      cells also occurred in Ammon's horn, subiculum and entorhinal cortex. Dendrites
      of immunoreactive cells were smooth and displayed a few small, faintly stained
      spines which were hard to identify in the light microscopic preparations, but
      were visible with electron microscopy. Substance P-positive dendrites were
      exclusively found in the hilar region and never observed in the upper two-thirds
      of the molecular layer of the dentate gyrus. Moreover, immunoreactive dendrites
      rarely penetrated the stratum lacunosum-moleculare of Ammon's horn. In the
      electron microscopic preparations, somal and dendritic features of substance P
      positive neurons were similar to those observed for GABAergic local circuit
      neurons. Axons of the substance P-immunoreactive local circuit neurons were thin
      and richly arborized in the upper two-thirds of the molecular layer of the
      dentate gyrus, in the stratum lacunosum-moleculare of Ammon's horn as well as in
      the subpial layers of the subicular complex and entorhinal cortex. Their
      terminals formed exclusively symmetric synapses with dendrites and spines.
      However, substance P-immunoreactive boutons were not found to make symmetric,
      axosomatic synapses on the granule cells of the dentate gyrus and very few were
      present on the pyramidal neurons of Ammon's horn, subicular complex, and
      entorhinal cortex. Hippocampal neurons, which were immunoreactive for substance
      P, also contained the neuropeptide somatostatin. However, not all of the
      somatostatin-containing neurons were substance P-immunoreactive. Thus, substance
      P-positive neurons are a subpopulation of somatostatin immunoreactive, GABAergic
      neurons. In conclusion, substance P-immunoreactive neurons are ideally suited for
      feed-back dendritic inhibition which may control the effectiveness of the main
      excitatory cortical input to the granule cells of the dentate gyrus and pyramidal
      neurons of the Ammon's horn.

PMID- 8867038
TI  - Layer-specific sprouting of commissural fibres to the rat fascia dentata after
      unilateral entorhinal cortex lesion: a Phaseolus vulgaris leucoagglutinin tracing
      study.
AB  - After unilateral entorhinal cortex lesion commissural fibres to the inner
      molecular layer of the rat fascia dentata are said to sprout into the former
      termination zone of entorhinal afferents. This sprouting process has not yet been
      demonstrated at the level of individual fibres. In the present study, Phaseolus
      vulgaris leucoagglutinin tracing was used to analyse the commissural projection
      to the inner molecular layer in rats with longstanding entorhinal cortex lesions.
      In comparison with controls, the commissural fibre plexus in the inner molecular
      layer had expanded by 20-45 microns outwards on the side of the entorhinal
      lesion. Unexpectedly, only a small number of axons arising from the bulk of
      commissural fibres in the inner molecular layer left the main fibre plexus and
      entered the outer molecular layer. Thus, there was still a clearly recognizable
      border between the Phaseolus vulgaris leucoagglutinin-labelled commissural fibre
      plexus in the inner molecular layer and the unstained outer molecular layer. The
      few commissural axons invading the outer molecular layer rarely branched but
      formed multiple en passant boutons, and occasionally exhibited growth cones. The
      data indicate that only few commissural fibres appear to be able to sprout beyond
      the border of their appropriate layer suggesting that the characteristic laminar
      specificity of hippocampal afferents is largely retained following
      deafferentation.

PMID- 8867039
TI  - In vivo regulation of specific GABAA receptor subunit messenger RNAs by increased
      GABA concentrations in rat brain.
AB  - This study has examined whether changes in endogenous GABA concentrations
      influence GABAA receptor subunit mRNA expression in vivo. Increased GABA
      concentrations were achieved by treating female rats with gamma-vinyl-GABA (15
      mg/100 g), an irreversible inhibitor of the GABA transaminase, daily for three
      days. High performance liquid chromatography analysis of brain punches from
      specific brain regions showed that gamma-vinyl-GABA treatment resulted in
      approximately two-fold increases in brain GABA content. Using in situ
      hybridization techniques with specific 35S-labelled oligonucleotides, the mRNA
      expression of the alpha 1, alpha 2, beta 2, beta 3, gamma 1 and/or gamma 2
      subunits of the GABAA receptor was quantified in various brain regions including
      the medial preoptic nucleus, bed nucleus of the stria terminalis, bed nucleus of
      the anterior commissure, supraoptic and paraventricular nuclei of the
      hypothalamus, globus pallidus and cingulate cortex. Silver grain density analysis
      showed that gamma-vinyl-GABA treatment induced a significant 35 and 49% decrease
      in gamma 1 mRNA expression in the medial preoptic nucleus and the principle
      encapsulated nucleus of the bed nucleus of the stria terminalis respectively, and
      a significant 20% decrease in alpha 2 mRNA expression in the cingulate cortex.
      Expression of alpha 2 and beta 3 in the former areas was unchanged as was alpha
      1, beta 2, beta 3 and gamma 2 subunit expression in the cingulate cortex.
      Elevation of brain GABA levels also resulted in a specific and significant 17%
      increase in gamma 2 mRNA expression in the supraoptic nucleus. In the globus
      pallidus, gamma-vinyl-GABA treatment induced a significant 29% increase in alpha
      1 mRNA expression combined with 19 and 30% decreases in beta 2 and gamma 2 mRNA
      expression, respectively. Levels of GABAA receptor subunits expressed in the bed
      nucleus of the anterior commissure (alpha 2, beta 3, gamma 1) and paraventricular
      nucleus (alpha 1, alpha 2, beta 2, gamma 2) were not changed by gamma-vinyl-GABA
      treatment. These results provide in vivo evidence for a region- and subunit
      specific regulation of GABAA receptor subunit mRNA levels following the elevation
      of brain GABA concentrations and suggest that endogenous GABA levels influence
      GABAA receptor subunit mRNA expression.

PMID- 8867040
TI  - Immunohistochemical localization of the cloned kappa 1 receptor in the rat CNS
      and pituitary.
AB  - Several lines of evidence have demonstrated the presence of three opioid receptor
      types in the CNS and periphery. These receptors are referred to as mu, delta and
      kappa, and have been implicated in a wide variety of functions. The present study
      examines the localization of the kappa 1 receptor, a region of the receptor that
      has little homology with mu and delta receptors. Immunohistochemical studies in
      Zamboni-fixed rat tissue demonstrate immunoreactive perikarya and/or fibers in
      such regions as the deep layers of the parietal, temporal and occipital cortex,
      parasubiculum, central and medial amygdala, bed nucleus stria terminalis, nucleus
      accumbens, olfactory tubercle, endopiriform nucleus, claustrum, hypothalamic
      nuclei, median eminence, midline thalamic nuclei, zona incerta, central gray,
      caudal linear and dorsal raphe, substantia nigra, pars reticulata, ventral
      tegmental area, parabrachial nucleus, spinal trigeminal nucleus, nucleus of the
      solitary tract, spinal cord and the dorsal root ganglia. Specific kappa 1
      receptor-like immunohistochemical staining is also observed in the pituitary,
      where immunoreactive perikarya and fibers are localized in the neural and
      intermediate lobes. Transfection and preabsorption controls suggest that the
      antibody is selective for the cloned kappa 1 receptor, and does not recognize mu
      or delta. This immunohistochemical localization corresponds well to previously
      described kappa 1 receptor mRNA and binding distributions and provides new
      insights into the cellular localization and pre- and postsynaptic organization of
      the kappa 1 receptor-like proteins in the rat brain and pituitary. The functional
      implications of these results are discussed in light of the kappa 1 receptors
      play in hormonal regulation, antinociception and reward.

PMID- 8867041
TI  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic denervation
      potentiates gabaergic inhibition in the mouse neostriatum in vitro.
AB  - Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's
      disease, we investigated the long-term effects of dopaminergic denervation on
      synaptic transmission in an in vitro slice preparation of the mouse neostriatum.
      In control mice, electrical stimulation elicited an antidromic potential (N1)
      followed by a synaptically mediated field potential (N2). In many slices, a third
      component (N3) was observed. Determination of the maximum stimulus intensities
      unveiled that in 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-pretreated
      animals, the stimulus strength necessary to evoke a maximum N2 response was
      significantly higher compared to control mice. Furthermore, 1-methyl-4-phenyl
      1,2,3, 6-tetrahydropyridine-pretreatment led to a less frequent appearance and/or
      to a reduction in the amplitude of the N3 component. Application of glutamate
      receptor agonists and antagonists revealed two additional differences between
      normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. (1)
      Comparison of the efficacy of the alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione
      demonstrated an increase in the inhibitory effect of 6-cyano-7-nitroquinoxaline
      2,3-dione in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. (2) In
      normal mice, removal of magnesium ions from the bathing solution invariably led
      to the appearance of late N-methyl-D-aspartate receptor-dependent synaptic
      components. There components were only slightly expressed or virtually absent in
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. The described
      differences between the electrophysiological and pharmacological properties of
      evoked field potentials in slices from normal and 1-methyl-4-phenyl-1,2,3, 6
      tetrahydropyridine-pretreated mice disappeared following blockade of GABAA
      receptor-dependent inhibition by bicuculline. In normal and 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-pretreated mice, bicuculline did not influence the
      amplitude of the N2 component, but invariably unmasked late synaptic components
      mediated by glutamate receptors. However, the potentiating effect of bicuculline
      was significantly stronger in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      pretreated mice compared to the controls. In the presence of bicuculline, the
      frequency of occurrence of the N3 component was identical in both groups.
      Furthermore, the apparent efficiency of 6-cyano-7-nitroquinoxaline-2,3-dione was
      no longer different. Application of bicuculline in the absence of magnesium ions
      resulted in a similar disinhibition of N-methyl-D-aspartate receptor-dependent
      late components as observed in the controls in the absence of bicuculline. The
      data demonstrate that chronic dopaminergic denervation reduces glutamate receptor
      dependent synaptic excitation in the mouse neostriatum. Since differences between
      normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice disappear
      in the presence of bicuculline, we conclude that this reduction in excitability
      is due to a potentiation of GABAA receptor-dependent inhibition.

PMID- 8867042
TI  - Differential effects of ventral striatal lesions on the conditioned place
      preference induced by morphine or amphetamine.
AB  - The present experiment examined the role of the ventral striatum in the rewarding
      effect of morphine and amphetamine by testing whether lesions of cell bodies
      within this region disrupt the development of a conditioned place preference to
      either drug. Bilateral, N-methyl-D-aspartate- or kainic acid-induced lesions of
      the ventral striatum block a conditioned place preference to amphetamine (1.5
      mg/kg x 3 pairings) but not to morphine (2 mg/kg x 3 pairings). Because both
      lesions spared anterior portions of the ventral striatum, we examined the effect
      of larger or more selective ventral striatal lesions on a conditioned place
      preference induced by morphine. Destruction of the entire ventral striatum
      reduced, but did not eliminate, a conditioned place preference to morphine,
      whereas selective lesions of the anterior ventral striatum were ineffective.
      These results indicate that the ventral striatum is not critically involved in
      morphine's rewarding effect and support the suggestion that the rewarding effects
      of opiates and stimulants do not involve identical neural substrates.

PMID- 8867043
TI  - Sulfonylurea-sensitive potassium current evoked by sodium-loading in rat midbrain
      dopamine neurons.
AB  - In Parkinson's disease, there is evidence of impaired mitochondrial function
      which reduces the capacity to synthesize ATP in dopamine neurons. This would be
      expected to reduce the activity of the sodium pump (Na+/K+ ATPase), causing
      increased intracellular levels of Na+. Patch pipettes were used to introduce Na+
      (40 mM in pipette solutions) into dopamine neurons in the rat midbrain slice in
      order to study the electrophysiological effects of increased intracellular Na+.
      We found that intracellular Na+ loading evoked 100-300 pA of outward current (at 
      60 mV) and increased whole-cell conductance; these effects developed gradually
      during the first 10 min after rupture of the membrane patch. Extracellular Ba2+
      reduced most of the outward current evoked by Na+ loading; this Ba(2+)-sensitive
      current reversed direction at the expected reversal potential for K+ (EK), and
      was also blocked by extracellular tetraethylammonium (30 mM) and intracellular
      Cs+ (which replaced K+ in pipette solutions). The sulfonylurea drugs glipizide
      (IC50 = 4.9 nM), tolbutamide (IC50 = 23 microM) and glibenclamide (1 microM) were
      as effective as 300 microM Ba2+ in reducing the K+ current evoked by Na+ loading.
      When recording with "control" pipettes containing 15 mM Na+, diazoxide (300
      microM) increased chord conductance and evoked outward current at -60 mV, which
      also reversed direction near EK. Effects of diazoxide were blocked by
      glibenclamide (1 microM) or glipizide (300 nM). Diazoxide (300 microM) and
      baclofen (3 microM), which also evoked K(+)-mediated outward currents recorded
      with control pipettes, caused little additional increases in outward currents
      during Na+ loading. Raising ATP concentrations to 10 mM in pipette solutions
      failed to significantly reduce currents evoked by diazoxide or Na+ loading,
      suggesting that these currents may not be mediated by ATP-sensitive K+ channels.
      Finally, Na+ loading using pipettes containing Cs+ in place of K+ evoked a
      relatively small outward current (50-150 pA at -60 mV), which developed gradually
      over the first 10 min after rupturing the membrane patch. This current was
      reduced by dihydro-ouabain (3 microM) and a low extracellular concentration of K+
      (0.5 mM instead of 2.5 mM), but was not affected by Ba2+. We conclude that
      intracellular Na+ loading evokes a current generated by Na+/K+ ATPase in addition
      to sulfonylurea-sensitive K+ current. This Na(+)-dependent K+ current is unusual
      in its sensitivity to sulfonylureas, and could protect dopamine neurons against
      toxic effects of intracellular Na+ accumulation.

PMID- 8867044
TI  - Involvement of nigral glutamatergic inputs in the control of seizures in a
      genetic model of absence epilepsy in the rat.
AB  - The reticular part of the substantia nigra is known to be a critical site in the
      control of epileptic seizures. Potentiation of the direct striatonigral GABAergic
      projection has been shown to suppress seizures in different animal models of
      epilepsy. Besides this GABAergic input, the substantia nigra receives
      glutamatergic inputs, especially from the indirect striatonigral pathway, via the
      subthalamic nucleus. To investigate the involvement of the nigral excitatory
      amino acid transmission in the remote control of non-convulsive generalized
      seizures, several drugs interacting with glutamatergic receptors were first
      injected into the substantia nigra pars reticulata in rats with spontaneous
      absence seizures. Blockade of N-methyl-D-aspartate receptors suppressed
      spontaneous generalized non-convulsive seizures in the rat, whereas blockade of
      non-N-methyl-D-aspartate receptors was without effect. Second, inhibition of the
      subthalamic projection by bilateral injections of a GABAergic agonist in this
      structure similarly suppressed absence seizures. These results suggest that
      excitatory amino acid inputs are critical in the triggering of the nigral control
      of generalized epilepsies. Furthermore, they support the hypothesis of a possible
      involvement of the subthalamonigral pathway in the control of generalized non
      convulsive seizures.

PMID- 8867045
TI  - Circling behavior elicited by cholinergic transmission in the substantia nigra
      pars compacta: involvement of nicotinic and muscarinic receptors.
AB  - The influence of cholinergic transmission within the substantia nigra pars
      compacta on circling behavior was assessed in male rats. Microinjection of
      physostigmine (6-37 nmol) into the caudal part of the substantia nigra pars
      compacta elicited a dose-dependent contralateral circling. The circling was
      inhibited 93 +/- 3% by the dopamine antagonist haloperidol (53 nmol) injected
      into the neostriatum 90 min before the injection of physostigmine (37 nmol) into
      the ipsilateral substantia nigra pars compacta. The effect of haloperidol was
      reversible, since the circling behavior was fully restored when physostigmine was
      applied to the same animals 24 h later. The circling was completely blocked when
      physostigmine (37 nmol) was applied simultaneously with the muscarinic M1
      antagonist pirenzepine (2 nmol). The M2 antagonist AF-DX 116 (2 nmol) only
      partially blocked the circling induced by a lower dose of physostigmine (12
      nmol). The nicotinic antagonist mecamylamine (5 nmol) also inhibited the
      circling, but only during the 5 min following co-injection of the drugs. These
      results indicate that endogenous acetylcholine stimulates muscarinic and
      nicotinic receptors of nigrostriatal dopaminergic neurons which, in turn,
      increase their firing rate and cause the circling behavior. We conclude that the
      pedunculopontine cholinergic neurons, which innervate the substantia nigra pars
      compacta, modulate the motor behavior by increasing the activity of dopaminergic
      nigrostriatal pathway.

PMID- 8867046
TI  - Melanin-concentrating hormone is a potent anorectic peptide regulated by food
      deprivation and glucopenia in the rat.
AB  - Melanin-concentrating hormone is a cyclic nonadecapeptide that is produced almost
      exclusively in neurons of the lateral hypothalamus and sub zona incerta areas
      while fibers are widespread in the rat brain. Such a localization strongly
      suggests that this peptide might participate as neurotransmitter/neuromodulator
      in the control of feeding behavior. In this study we examined first the influence
      of rat melanin-concentrating hormone on feeding behavior at different times
      either in the light or in the dark period (light off at 18.00 h) of the day in
      fed Wistar rats. Intracerebroventricular injection of rat melanin-concentrating
      hormone (1-100 ng per rat) at 18.00 h reduced food consumption as early as 2 h
      after injection and for the next 24 h. In addition, similar anorectic effect was
      noted after bilateral administration of 1 ng melanin-concentrating hormone into
      the lateral hypothalamic area at 11.30 h but not at 16.30 h. These findings
      strongly suggest that rat melanin-concentrating hormone may exert inhibitory
      control over food intake behavior depending on the circadian rhythm. Second, we
      investigated the modifications induced by food deprivation/refeeding on melanin
      concentrating hormone messenger RNA levels in Wistar rats. Total RNA was isolated
      from whole hypothalamic dissections and the contents of melanin-concentrating
      hormone messenger RNA, beta-actin messenger RNA (taken as sample control) and
      neuropeptide Y messenger RNA (taken as control of food-deprivation paradigms)
      were assessed by using northern blotting. The time-course of messenger RNA
      expression was determined in groups of rats deprived for 24, 48 and 72 h and
      revealed a three-fold induction of melanin-concentrating hormone messenger RNA by
      24 and 48 h, with reduced increase at 72 h. As expected, the same treatment led
      to a three-fold increase in neuropeptide Y messenger RNA content by 48 and 72 h.
      Refeeding groups of animals for up to 72 h after 24 h of food deprivation
      resulted in full restoration of melanin-concentrating hormone messenger RNA
      levels by 24 h. Strikingly, a large range of variations in melanin-concentrating
      hormone messenger RNA content between individuals was observed in food-deprived
      versus controls or refed rats suggesting that genetic or environmental factors
      may alter response in melanin-concentrating hormone gene activity after food
      deprivation. Finally, we investigated the effects of short-term glucoprivation
      induced by intraperitoneal administration of either 2-deoxy-D-glucose or insulin
      on melanin-concentrating hormone messenger RNA expression. A transitory increase
      in melanin-concentrating hormone messenger RNA content was noted 1 h after 2
      deoxy-D-glucose injection while melanin-concentrating hormone messenger RNA
      levels rose two-fold only 5 h after insulin treatment. These results indicate
      that 2-deoxy-D-glucose and insulin activate melanin-concentrating hormone gene
      expression through likely distinct regulatory pathways.

PMID- 8867047
TI  - Arginine vasopressin release by acetylcholine or norepinephrine: region-specific
      and cytokine-specific regulation.
AB  - Interferon-alpha and transforming growth factor-beta 1 have been detected in the
      brain, suggesting their possible regulatory functions. In the present study, we
      evaluated the effects of these cytokines on the in vitro release of arginine
      vasopressin, previously reported to be sensitive to neurotransmitters such as
      acetylcholine, norepinephrine, and corticotropin releasing hormone as well as to
      cytokines interleukin-1 and interleukin-2. Interferon-alpha was found to enhance
      arginine vasopressin release from both hypothalamus and amygdala, as was
      dibutyryl cyclic GMP. Blockade of nitric oxide synthase antagonized the
      interferon-alpha induced arginine vasopressin release from the amygdala but not
      from the hypothalamus. Transforming growth factor-beta 1 had no effect on basal
      release of arginine vasopressin, nor on the arginine vasopressin-release induced
      by interferon-alpha, interleukin-2 or norepinephrine, but selectively blocked the
      acetylcholine-induced release in both hypothalamus and amygdala. When the release
      of arginine vasopressin induced by interferon-alpha, interleukin-2, acetylcholine
      and norepinephrine was probed with inhibitors of guanylate cyclase, the
      interactions exhibited regional selectivity: neither the interleukin-2-induced
      arginine vasopressin release from hypothalamus, nor the norepinephrine-induced
      release of arginine vasopressin from either amygdala or hypothalamus was affected
      by guanylate cyclase inhibitors, but all other arginine vasopressin releasers
      were blocked. Taken with previous reports that interferon-alpha will enhance
      hypothalamic corticotropin releasing hormone release, our results suggest that
      arginine vasopressin release enhanced by interferon-alpha may also contribute to
      the activation of the hypothalamic-pituitary axis, while the ability of
      transforming growth factor-beta 1 to diminish the arginine vasopressin released
      by acetylcholine could mediate some of this cytokine's central effects. The
      extension of these neurotransmitter-cytokine interactions to the amygdala may
      provide an additional basis for interactions between neuronal and immune systems.

PMID- 8867048
TI  - Central infusions of brain-derived neurotrophic factor and neurotrophin-4/5, but
      not nerve growth factor and neurotrophin-3, prevent loss of the cholinergic
      phenotype in injured adult motor neurons.
AB  - Neurotrophic factors are molecules that prevent neuronal degeneration and
      regulate neuronal phenotype during either development or adulthood. Relatively
      little is known about the comparative responsiveness of injured adult central
      nervous system motor neurons to various neurotrophic factors. In the present
      study we examined the effects of four members of the neurotrophin family on
      injured adult motor neurons. Nerve growth factor, brain-derived neurotrophic
      factor, neurotrophin-3 or neurotrophin-4/5 were infused intracerebroventricularly
      into adult rats following transection of the motor hypoglossal nerve. Two weeks
      after axotomy, brain-derived neurotrophic factor and neurotrophin-4/5 completely
      prevented the loss of the cholinergic phenotype in hypoglossal motor neurons (97
      +/- 11% and 99 +/- 5%, respectively) as assessed by choline acetyltransferase
      immunolabeling. In contrast, nerve growth factor and neurotrophin-3 exerted no
      protective effect. The low-affinity p75 neurotrophin receptor, capable of binding
      all four neurotrophins, was re-expressed in injured hypoglossal neurons; the
      majority of injured hypoglossal neurons also express trkB receptors but not trkA
      or trkC receptors. Thus, injury-induced responses to neurotrophins in adult motor
      neurons are mediated by trk receptors and their agonists, but may or may not also
      require low-affinity p75 neurotrophin receptors. Intracerebroventricular
      infusions of trkB agonists may be a useful means of targeting multiple and
      distantly separated populations of motor neurons for neurotrophic factor therapy.

PMID- 8867049
TI  - Antibodies directed against the beta 1-integrin subunit and peptides containing
      the IKVAV sequence of laminin perturb neurite outgrowth of peripheral neurons on
      immature spinal cord substrata.
AB  - Neuron-substratum interactions regulating axon growth in the developing central
      nervous system of the rat have been studied by means of an in vitro bioassay: the
      tissue section culture. We have previously shown that purified chicken sensory or
      sympathetic neurons grown on natural substrata consisting of cryostat sections of
      neonatal rat spinal cord elaborate numerous long neurites [Sagot et al. (1991)
      Brain Res. 543, 25-35]. Perturbation experiments, in which neuron-substratum
      interactions are modified by antibodies and peptides, have allowed us to analyse
      some of the molecular determinants which control neurite outgrowth in this
      system. Antibodies directed against the beta 1-integrin subunit, one of the
      neuronal receptors for extracellular matrix molecules, reduced the percentage of
      growing neurons by about 30% and the length of neurites by about 50%. In
      contrast, antibodies directed against laminin-1 or fibronectin, two extracellular
      matrix proteins transiently expressed in various areas of the developing central
      nervous system, were unable to block neurite outgrowth. Paradoxically, a peptide
      containing the IKVAV sequence, which mimics an active sequence of the laminin
      alpha 1 chain responsible for neurite extension, also blocked neurite outgrowth
      on neonatal spinal cord substrata. These results indicate that integrin receptors
      containing the beta 1 subunit may play a role in regulating axon growth in the
      developing nervous system. Among the putative extracellular matrix ligands for
      these receptors, laminin and fibronectin do not appear as prominent candidates in
      the neonatal spinal cord. However, our data also suggest that the developing
      central nervous system may contain neurite outgrowth-promoting proteins carrying
      the IKVAV sequence, different from laminin-1.

PMID- 8867050
TI  - Early postnatal muscle contractile activity regulates the carbonic anhydrase
      phenotype of proprioceptive neurons in young and mature mice: evidence for a
      critical period in development.
AB  - Carbonic anhydrase activity, a marker of mouse proprioceptive neurons in adult
      dorsal root ganglia, is first detectable in the perinatal period, increases until
      postnatal day 60 and remains stable in adulthood. The onset of carbonic anhydrase
      staining begins after the neurons have made connections with their targets
      suggesting that neuron-target interactions regulate carbonic anhydrase phenotype
      development. To examine this possibility, we first analysed carbonic anhydrase
      expression in mdx mice which are characterized by a massive but reversible
      degeneration of skeletal muscle concomitant with the carbonic anhydrase
      ontogenesis. Neuronal carbonic anhydrase expression in mdx mice stopped
      developing when the period of muscular degeneration-regeneration began.
      Furthermore this alteration persisted during adulthood. We then analysed carbonic
      anhydrase expression in fifth lumbar dorsal root ganglion of developing control
      mice before and after surgical procedures that might interfere with central and
      peripheral target influences on dorsal root ganglion neurons. Central
      disconnection (dorsal rhizotomy) did not affect the development of carbonic
      anhydrase activity. Disrupting neuron-peripheral target interactions by sciatic
      nerve transection or blocking muscle contraction by tenotomy stopped the
      development of neuronal carbonic anhydrase content. Finally, recovery was
      monitored following sciatic nerve crush. In adults, recovery of carbonic
      anhydrase activity was obtained after functional recuperation; similar
      manipulations during the first month of life induced irreversible alteration of
      the carbonic anhydrase phenotype. These results show that the development of
      carbonic anhydrase activity in proprioceptive neurons is regulated by neuron
      muscle interactions (i.e. muscle contraction). They also provide evidence for a
      critical period in the development of the carbonic anhydrase phenotype. We
      suggest that these two mechanisms are responsible for the altered carbonic
      anhydrase phenotype of the dorsal root ganglion neurons in mdx mice, a model of
      human muscular dystrophy.

PMID- 8867051
TI  - Autoradiographic localization of functional muscarinic receptors in the rat
      superior cervical sympathetic ganglion reveals an extensive distribution over non
      synaptic surfaces of neuronal somata, dendrites and nerve endings.
AB  - Fast synaptic transmission in sympathetic ganglia is mediated by acetylcholine,
      acting on nicotinic receptors, yet muscarinic receptors are also present and are
      involved in the production of slow postsynaptic potentials. In order further to
      elucidate the role of muscarinic receptors in ganglionic transmission their
      distribution in the rat superior cervical sympathetic ganglion was investigated
      autoradiographically by use of the tritiated irreversible muscarinic ligand
      propylbenzilylcholine mustard. It was observed that this agent blocked the
      carbachol-evoked hydrolysis of inositol phospholipids in the ganglion and that
      this response to carbachol is itself inhibitable by selective muscarinic
      antagonists with a potency sequence which indicates involvement primarily of M1
      receptors. Light microscope autoradiography showed that labelling inhibitable by
      atropine and by the M1-selective muscarinic antagonist pirenzepine was
      essentially confined to the margins of neuronal somata and regions of dendritic
      arborization, which include synaptic contacts. Quantitative electron microscope
      autoradiography showed that binding of the radioligand, of which approximately
      70% was inhibitable by atropine and 68% by pirenzepine, was associated
      predominantly with surface membranes of neuronal somata, dendrites, other
      neurites (including axons and uncharacterized dendrites) and nerve terminal
      profiles, in the approximate ratios 95:85:52:45. Of the inhibitable binding over
      neuronal membranes in the ganglion little more than 3% was found to be
      synaptically located, and this involved para- or peri-synaptic regions of nerve
      terminal contacts rather than the specialized synaptic zone. About 5% of the
      inhibitable binding over neuronal membranes involved non-synaptic surfaces of
      nerve terminals and preterminal axon segments; almost 70% was distributed over
      non-synaptic surfaces of neuronal somata and dendrites, and about 21% upon other
      neurites. Binding sites were found not to be more highly concentrated at or
      adjacent to synapses than over other regions of neuronal surface membranes. About
      50%, possibly more, of the binding on non-synaptic surfaces of nerve endings, and
      about 7% of binding upon dendritic membranes, was of non-M1, possibly M2 type,
      inhibitable by atropine but not by pirenzepine. Non-synaptic neuro-neuronal
      appositions, which involve dendrites and somata and often lie adjacent to
      synapses, showed rather more than twice the binding expected for each membrane
      individually; and neuronal membrane exposed to basal lamina lining ganglionic
      tissue spaces showed high levels of binding. Little inhibitable binding was seen
      over membranes of satellite and Schwann cells, or over cytoplasmic territories or
      ganglionic interstitial tissue. A model was constructed of the distribution of
      label, which showed that the observed results for total binding could be
      approximately matched by assuming the following relative densities of ligand
      binding sites: interstitial tissue space and supporting cells 1, soma cytoplasm
      3, cytoplasm of dendrites, neurites and nerve terminals 4.5, surfaces of
      mesodermal elements 15, surfaces of neurites and nerve endings including sites of
      synapse 45, surfaces of dendrites 90, surfaces of neuronal somata 120, non
      synaptic neuro-neuronal appositions 180. It is concluded that functional
      muscarinic receptors in this sympathetic ganglion, predominantly of the M1 type
      linked with slow depolarizations, but including some non-M1 receptors, are widely
      distributed over non-synaptic surfaces of the neuronal somata and dendrites and
      are not concentrated at synapses. Presynaptic autoreceptors are also present, of
      which half or more are of non-M1, possibly M2, type which might be inhibitory.
      The presence of M4 receptors is not excluded...

PMID- 8867052
TI  - Comparison of cytosolic Ca2+ and exocytosis responses from single rat and bovine
      chromaffin cells.
AB  - The relationship between cytosolic Ca2+ and catecholamine secretion during
      stimulus-secretion coupling has been examined at individual chromaffin cells
      isolated from the cow and rat. Vesicular catecholamine exocytosis was determined
      via amperometric measurements with carbon fibre microelectrodes and fura-2 was
      used for simultaneous fluorescent monitoring of cytosolic Ca2+ at the same cell.
      Individual secretory vesicles in cells from the two species were found to release
      similar amounts of catecholamine. In addition, the time courses for secretion
      from individual vesicles was similar with rat and bovine chromaffin cells. The
      total quantity of catecholamine released and the change in cytosolic Ca2+ were
      also similar in response to exposure to K+ (60 mM), 1,1-dimethyl-4
      phenylpiperazinium (50 microM), and histamine (50 microM), although both
      responses were more prolonged following 1,1-dimethyl-4-phenylpiperazinium and
      histamine at bovine cells. Agents that mobilize intracellular Ca(2+)-stores such
      as methacholine, caffeine and bradykinin resulted in different cytosolic Ca2+ and
      exocytosis responses at the rat and bovine chromaffin cells. Results indicate a
      heightened Ca(2+)-store activity or a more filled state in chromaffin cells from
      the rat. The results of this study clearly show that single-cell techniques can
      be used to characterize stimulus-secretion coupling. The requirement for lower
      numbers of cells with these techniques means that chromaffin cells from rodents
      can be routinely employed. This can be advantageous to minimize biological
      variability which occurs with organs obtained from slaughter houses and enables
      the investigation of genetically-altered animals.

PMID- 8867053
TI  - Retinoic acid treated P19 embryonal carcinoma cells differentiate into
      oligodendrocytes capable of myelination.
AB  - Retinoic acid treatment of P19 embryonal carcinoma cells induces their
      differentiation into cultures containing neurons and astrocytes. We present two
      lines of experimentation indicating that oligodendrocytes also develop from
      retinoic acid-treated P19 cells. We isolated an immortal cell line from retinoic
      acid-treated P19 cell cultures whose proliferation is dependent upon epidermal
      growth factor. Upon removal of the growth factor these cells differentiate into
      both astrocytes and oligodendrocytes as determined by immunostaining with
      antibodies to the astrocyte marker glial fibrillar acidic protein and the
      oligodendrocyte markers, myelin associated glycoprotein and 2', 3'-cyclic
      nucleotide 3'-phosphodiesterase. This cell line appears to be a bi-potential
      glial precursor. We also found that oligodendrocytes developed directly from P19
      cells when retinoic acid-treated cells were transplanted into the brains of
      neonatal rat pups. Cells that developed into oligodendrocytes migrated into fiber
      bundles up to several millimeters from the site of the graft. These P19-derived
      oligodendrocytes appeared to myelinate axons from host neurons. Thus, retinoic
      acid-treated P19 cells differentiate into neurons, astrocytes and
      oligodendrocytes, the three cell types that normally develop from embryonic
      neuroectoderm, indicating that these cell cultures differentiate in a fashion
      closely resembling that of embryonic neuroectoderm.

PMID- 8867054
TI  - Energy metabolism of adult astrocytes in vitro.
AB  - In this study we established cultures of astrocytes from the forebrain of the
      adult rat. The homeostatic regulatory mechanisms of the aerobic and anaerobic
      pathways of energy metabolism in these cells showed that adult astrocytes express
      many of the regulatory properties previously demonstrated in neonatal astrocytes.
      Changes in mitochondrial respiration and ATP production were readily evident upon
      incubation with the relevant substrates. Inhibition of mitochondrial respiration
      led to a compensatory increase in anaerobic glycolysis as evidenced by an
      increased release of lactate. We assessed the role of cytosolic calcium in the
      regulation of the mitochondrial energy metabolism. Increases in cytosolic calcium
      concentration in response to ATP or stimulation of mechanical receptors were
      followed by depolarizations of the mitochondrial membrane potential, whose
      magnitude reflected the amplitude of the cytosolic calcium response. The changes
      in mitochondrial membrane potential were largely dependent on the presence of
      external calcium. These results provide the first evidence of a signalling
      mechanism in astrocytes by which changes in cytosolic calcium mediate changes in
      respiration, possibly through mitochondrial calcium uptake and subsequent
      activation of several mitochondrial dehydrogenases. This signalling pathway would
      thus ensure that energy demands due to changes in cytosolic calcium
      concentrations are met by increases in energy production through increases in
      mitochondrial oxidative phosphorylation.

PMID- 8867055
TI  - Mechanisms of intracellular calcium regulation in adult astrocytes.
AB  - Microfluorimetric techniques were used to measure changes in intracellular
      calcium in astrocytes cultured from the forebrain of the adult rat. Application
      of ATP consistently raised intracellular calcium. The response persisted in the
      absence of extracellular calcium, but then quickly declined upon repeated agonist
      application. Thapsigargin abolished responses to nucleotides following depletion
      of the endoplasmic reticular calcium stores. Calcium release was inhibited by
      caffeine, but was dramatically increased through inositol phosphate receptor
      sensitization by the sulphydryl reagent thimerosal. Responses to repeated
      nucleotide applications resulted in a gradual decline of peak calcium
      concentrations, suggesting a (post)receptor-mediated desensitization or gradual
      depletion of the internal calcium stores. Subsequent application of ionomycin
      suggested intracellular calcium depletion as the relevant mechanism. Depletion of
      the internal calcium stores with ATP, ionomycin or thapsigargin failed to reveal
      a calcium influx pathway. These results suggest that the capacitative mechanism
      of calcium entry does not operate in response to nucleotide receptor activation
      in these cells, and that the immediate refilling of the internal calcium stores
      is primarily determined by re-uptake of cytosolic calcium into the endoplasmic
      reticulum. A complete refilling of this calcium store by extracellular calcium
      may be a much slower process. Control of these signal transduction pathways is
      crucial to the maintenance of the calcium/energy homeostasis of the adult
      astrocyte in the central nervous system.

PMID- 8867057
TI  - Paucity of P-zones in striatal grafts prohibit commencement of clinical trials in
      Huntington's disease.

PMID- 8867056
TI  - Co-localization of secretoneurin immunoreactivity and macrophage infiltration in
      the lesions of experimental autoimmune encephalomyelitis.
AB  - Secretoneurin, a novel neuropeptide, has recently been shown to attract
      monocytes. In our present study we have tested whether the local presence of
      secretoneurin within the CNS of the rat may influence the topographical
      distribution of inflammatory infiltrates in acute T-cell mediated
      encephalomyelitis. Experimental allergic encephalomyelitis was induced by passive
      transfer of myelin basic protein-reactive T-lymphocytes and the distribution of T
      cells and macrophages was studied at day 3, 4 and 7 after transfer. In the same
      sections secretoneurin immunoreactivity was visualized by immunohistochemistry. A
      clustering of macrophages, but not of T-lymphocytes, was seen at sites of
      secretoneurin immunoreactivity in all stages of experimental autoimmune
      encephalomyelitis. Our data indicate for the first time that local neuropeptides
      may play a role in leucocyte recruitment into inflammatory lesions of the CNS.

PMID- 8867058
TI  - What is needed versus what would be interesting to know before undertaking neural
      transplantation in patients with Huntington's disease.

PMID- 8867059
TI  - Anophelines of Siliguri-Naxalbari block, Darjeeling, West Bengal.
AB  - A systematic survey has been carried out during 1993-94 to study the occurrence
      and distribution of anopheline mosquitoes in Siliguri-Naxalbari block of
      Darjeeling district. The anopheline fauna of this region consists of 13 species,
      namely, An. vagus, An. culicifacies, An. annularis, An. barbirostris, An.
      subpictus, An. maculatus, An. tessellatus, An. jamesii, An. aconitus, An.
      "hyrcanus" group, An. karwari, An. fluviatilis and An. jeyporiensis among which
      the first five species forms the major bulk (92%). All the species showed
      preference to cattlesheds than human-habitation for resting. The ratio between
      morning and evening collection was 1:0.87.

PMID- 8867060
TI  - Epidemiological observations on malaria in villages of Buhari PHC, Surat,
      Gujarat.
AB  - Investigations were carried out in the villages of Buhari PHC, Surat district,
      Gujarat to determine factors responsible for high prevalence of P. falciparum.
      The area is well-known for sugarcane cultivation, industrialization and frequent
      movement of labourers. The slide positivity rate (44.24%) and P. falciparum
      infections (95.37%) were significantly high. The children of 5-9 yrs of age group
      suffered maximum from malaria. The infection in children was found associated
      with splenomegaly also. High falciparum infection (82.35%) was found in labourers
      camping near villages out of which 90% afebrile cases were reported which were
      silent carriers and source of transmission. Chloroquine was effective in 75%
      cases despite of existence of resistant falciparum strain. Among seven anopheline
      species encountered, An. culicifacies was predominant and found breeding in most
      of the breeding sites. The status of the insecticide spray and its receptivity
      among the community were poor. The investigation led to the conclusion that
      adequate measures are required to deal with migratory labourers, improper
      insecticide coverage, poor surveillance and mass ignorance.

PMID- 8867061
TI  - Bionomics of vector anophelines in District Naini Tal, Uttar Pradesh.
AB  - Breeding behaviour and seasonal prevalence of vector anopheline in different
      habitats associated with rice land agroecosystem of terai and bhabar area of
      District Naini Tal was studied from July 1992 to June 1994. Adult prevalence in
      both the areas shows two distinct An. fluviatilis peaks in the months of March
      and October and the breeding places for the species were pokhars in bhabar and
      stream and irrigation drains in terai. Prevalence of adult An. culicifacies was
      observed during July to August in bhabar and April and August in terai. In bhabar
      high immature density of An. culicifacies was noted mainly in tanks, pokhars and
      paddy fields (early transplantation period). In terai high immature density of
      An. culicifacies was noted in stream, while low in paddy fields. Higher
      prevalence of immatures and adult anopheline vectors coincide with peak malaria
      incidence in both the areas. In bhabar in the months of August and September
      large number of malaria cases were contributed by An. culicifacies and in
      November by An. fluviatilis. In terai, malaria cases in April and from June to
      September were contributed by An. culicifacies, whereas An. fluviatilis might be
      responsible for transmission in October.

PMID- 8867062
TI  - Application of simple peptide ELISA for stratification of malaria endemicity.
AB  - A serological investigation was conducted in north India to determine malaria
      endemicity based on the antibody levels against a nonapeptide RI (EENVEHDA-Cys)
      from the P. falciparum antigen Pf 155/RESA. P. falciparum sonicated crude antigen
      was also used in the study. Subjects of all age groups from various strata of
      malaria endemicity were included in this study. A total of 4273 finger prick
      blood samples from 49 villages of five districts were collected during January to
      March 1991 which is a non-transmission season and the antibody levels were
      estimated by ELISA. Although a good correlation was found between the antibody
      titre to the RI peptide and that to the crude antigen, the most consistent
      results were obtained with the RI peptide. When compared with the annual parasite
      index (API) values, an established method for defining malaria endemicity, mean
      anti-RI antibody titres obtained from several villages within a single zone
      correlated (r = 0.94, p = 0.023) with mean API value of the area. Thus, our
      results suggest that by using the RI peptide as antigen in seroepidemiology, it
      is possible to stratify malaria endemicity. We didn't distinguish between
      endemicity of Pv and Pf since each area experiences cycle of transmission of P.
      vivax followed by P. falciparum and our sera were from individuals having no
      fever.

PMID- 8867063
TI  - Drug resistant Plasmodium falciparum in Mandla District, Madhya Pradesh.

PMID- 8867064
TI  - The study of neurological disorders using positron emission tomography and single
      photon emission computed tomography.

PMID- 8867065
TI  - Neuroprotective effect of various cytokines on developing spinal motoneurons
      following axotomy.
AB  - Ciliary neurotrophic factor (CNTF), a multipoietic factor, on a variety of
      neurons, prevents axotomy-induced motoneuron loss and can improve the outcome of
      murine motor neuron disease (MND). We carried out a study to determine whether
      other cytokines rescue spinal motoneurons from axotomy-induced cell death.
      Unilateral sciatic nerve was transected in neonatal rats. Two doses of
      recombinant murine cholinergic differentiation factor/leukemia inhibitory factor
      (CDF/LIF), recombinant rat CNTF, recombinant human granulocyte-colony stimulating
      factor (G-CSF), recombinant human interleukin-6 (IL-6), recombinant human tumor
      necrosis factor beta (TNF beta), or vehicle were administered daily for 2 weeks
      by intraperitoneal injection. After treatment, the number of spinal motoneurons
      was determined at the level of L4-5 segments. In comparison with vehicle, the
      higher doses of CDF/LIF, CNTF, and IL-6, and the lower doses of CDF/LIF and IL-6
      significantly retarded the loss of motoneurons. G-CSF and TNF beta failed to
      inhibit motoneuron death. CDF/LIF and IL-6 rescued motoneurons from the
      retrograde death following axotomy, in a similar manner to CNTF. These results
      provide evidence that several cytokines may have therapeutic potential in human
      axonopathy or MND.

PMID- 8867066
TI  - Sural nerve myelinated fiber density differences associated with meaningful
      changes in clinical and electrophysiologic measurements.
AB  - New forms of therapy for diabetic and other neuropathies may prevent, stabilize,
      or ameliorate loss of nerve fibers. Clinically meaningful changes in mean
      Neurological Disability Score (NDS), and the associated mean change of
      electrophysiologic attributes have been described in diabetic polyneuropathy. It
      is unknown what magnitude of myelinated fiber (MF) density change is associated
      with these meaningful changes of clinical and electrophysiologic alterations. In
      18 diabetics and 5 normal controls associations between the mean NDS, summated
      (ulnar, peroneal and tibial) compound muscle action potential (sigma CMAP),
      summated (ulnar and sural) sensory nerve action potential (sigma SNAP), sural
      SNAP, and MF density in the sural nerve, were assessed using linear regression
      analyses. Values were corrected for age and sex. For a decrease of: 2 points in
      the mean NDS (minimum clinically detectable change), MF density decreased by
      approximately 200 fibers/mm2 (p < 0.001) 1 mV in the mean sigma CMAP (sum of the
      ulnar, peroneal and tibial CMAP amplitudes), MF density decreased by 160
      fibers/mm2 (p < 0.01) 1 microV in the mean sigma SNAP (sum of ulnar and sural
      SNAP amplitudes), MF density decreased by approximately 70 fibers/mm2 (p < 0.001)
      1 microV in the mean sural SNAP, MF density decreased by approximately 150
      fibers/mm2 (p < 0.01). Changes in sensory detection thresholds were also
      associated with a measurable change in the MF density. A quantifiable association
      exists between the magnitude of change in density of MF, and a meaningful
      alteration in mean NDS and various electrophysiologic parameters. Knowledge of
      this is needed to assess the statistical power of a clinical trial in which
      density of myelinated fibers is an outcome measurement.

PMID- 8867067
TI  - Developmental patterns of neuronal thread protein gene expression in Down
      syndrome.
AB  - Neuronal thread proteins (NTP) are a group of immunologically related molecules
      expressed in brain and neuroectodermal tumor cell lines. NTP gene expression is
      up-regulated and NTP molecules accumulate in Alzheimer's disease (AD) brains,
      pathological states associated with regenerative neuritic sprouting, and during
      brain development. To investigate the role of NTP over-expression in AD, we
      examined NTP immunoreactivity in brains from differently aged individuals with
      Down syndrome, since patients with Down syndrome nearly always develop AD
      neuropathology and dementia. Using SMI monoclonal antibodies to neurofilament
      protein, we detected age-associated increases in neurofilament immunoreactive
      (SMI-positive) neurites in Layers I and II of the cerebral cortex beginning at 1
      year of age, followed by SMI-positive neurofibrillary tangles beginning at age 5
      years, and then SMI-positive plaques beginning in the third decade. Increased NTP
      immunoreactivity in Down syndrome brains began in the second decade, prior to
      establishment of widespread AD neurodegeneration (Down syndrome + AD), and at an
      age when low-level or absent NTP expression was observed in control brains.
      Analysis of SDS and Triton X-100-treated histological sections and tissue
      extracts demonstrated that a largely insoluble, denaturation-resistant form of
      NTP accumulates in both Down syndrome + AD and AD brains. The findings provide
      further evidence that abnormal NTP expression and accumulation in brain may be an
      early marker of AD neurodegeneration in Down syndrome.

PMID- 8867068
TI  - Magnetic resonance imaging and spectroscopy of progressive cerebral involvement
      in Kearns Sayre Syndrome.
AB  - Kearns Sayre Syndrome (KSS) belongs to the group of so called 'mitochondrial
      encephalopathies'. Magnetic resonance imaging (MRI) and magnetic resonance
      spectroscopy (MRS) may have the potential to noninvasively detect and monitor
      disease specific cerebral involvement, as we wish to demonstrate in a patient
      whom we have followed for 3.5 years. At first presentation with incomplete
      external ophthalmoplegia, ptosis, pigmentary retinopathy and impaired hearing MRI
      demonstrated ill defined areas of symmetric T2-prolongation in the dorsal parts
      of the mesencephalon, the pons and in both cerebellar hemispheres. While the
      patients clinical symptoms deteriorated, including the onset of dysphagia, signal
      abnormalities spread downwards into the medulla oblongata involving the
      glossopharyngeal nuclei and supratentorially into the white matter. Proton MRS
      performed with the PRESS sequence (TR/TE 1500/136 ms) in the area of white matter
      damage showed a doublet at 1.33 ppm, which is characteristic for the presence of
      lactate. Our findings suggest MRI abnormalities to increase in parallel with
      neurologic progression of KSS and confirm the utility of 1H-MRS in supporting
      mitochondrial respiratory chain insufficiency as the underlying cause of
      parenchymal alterations.

PMID- 8867069
TI  - Vascular pathology in three cases of progressive cognitive deterioration.
AB  - The clinical condition known as vascular dementia remains poorly defined. Few
      studies have attempted a correlative link between the clinical syndrome and the
      structural abnormalities of the brain. Classically the clinical progression of
      the vascular dementing process is thought to be a multi-step process punctated by
      repeated episodes of ischemia, that are clinically expressed as strokes. In most
      instances it has been assumed that the substrate of vascular dementias consists
      of atherothrombotic infarcts. The objective of this report is to illustrate 3
      cases of progressive (rather than stepwise) cognitive deterioration without
      clinical evidence of stroke, evolving over a period of several years, in which
      there were prominent vascular lesions. A complete autopsy and detailed
      neuropathologic examination demonstrated cerebral vascular lesions involving
      small arterial vessels (< 200 microns in diameter). The lesions consisted of
      moderate-to-severe arteriolosclerosis in two cases, and mild-to-moderate
      arteriolosclerosis in a case of Alzheimer's disease with severe cerebral amyloid
      angiopathy. Parenchymal lesions consisted of small cortical and subcortical
      infarcts, most of them smaller than 0.1 cm in average diameter, and subcortical
      leukoencephalopathy severe in two cases and mild-to-moderate in the third case.
      Severe atherosclerosis not accompanied by large infarcts was also present in one
      case. Arterial changes affecting small, distal branches causing sometimes small
      parenchymal lesions in association with diffuse cerebral white matter disease,
      appear to be the anatomical substrate that accompanies progressive cognitive
      impairment in some patients who are frequently diagnosed with Alzheimer's disease
      because in their clinical records there is neither history of strokes nor
      stepwise progression of symptoms.

PMID- 8867070
TI  - X-linked bulbar and spinal muscular atrophy, or Kennedy disease: clinical,
      neurophysiological, neuropathological, neuropsychological and molecular study of
      a large family.
AB  - We report the clinical, neurophysiological, neuropsychological, neuropathological
      and molecular findings in a large family with X-linked bulbar and spinal muscular
      atrophy (X-BSMA). Molecular study, performed in 28 family members, showed an
      increase in the number of CAG repeats in 6 affected males (including 2
      presymptomatic patients), and in 10 females, of whom 5 were obligate carriers.
      All symptomatic patients showed, besides the typical manifestation of X-BSMA,
      neurophysiological signs of sensory nerve involvement, and abnormal findings in
      neuropsychological tests. Sural nerve biopsy, performed in two patients, was
      consistent with axonal atrophy and slow-rate degeneration, with secondary
      demyelination. Neurophysiological alterations were also present in 6 out of 8
      carriers, consisting of neurogenic EMG changes in 3 cases and abnormal sensory
      action potentials (SAP) and reduced conduction velocity of the sural nerve in 3
      cases. Abnormalities of at last two neuropsychological tests were found in 6 out
      of 8 carriers. Alterations of the sensory nerves in X-BSMA patients have been
      previously reported in some cases; however, we demonstrate for the first time
      sensory nerve involvement also in carriers. Evidence of central nervous system
      involvement, with neuropsychological impairment in all symptomatic patients and
      in some carriers, is another feature of this family, not previously reported in X
      BSMA. In spite of the variable phenotypic features, the number of CAG repeats
      ranged from 40 to 44 in the affected patients, indicating that phenotypic
      expression was not related to the size of the mutation, but was probably age
      related.

PMID- 8867071
TI  - Spinal and bulbar muscular atrophy: androgen receptor dysfunction caused by a
      trinucleotide repeat expansion.
AB  - Kennedy's disease (spinal and bulbar muscular atrophy) is an X-linked form of
      motor neuron disease that affects adult men. The syndrome is characterized by
      progressive atrophy of the limb muscles, pelvic and shoulder girdles and
      dysphagia and dysarthria, and is caused by the degeneration of spinal and bulbar
      motor neurons. Kennedy's disease is caused by a trinucleotide repeat expansion of
      a CAG repeat in exon A of the androgen receptor gene, and is one of a group of
      neurological diseases caused by trinucleotide repeat expansions in different
      genes. The mutation in Kennedy's disease involves an increased number of
      glutamine residues in the amino-terminal domain of the receptor. Point mutations
      and deletions in the androgen receptor gene cause androgen insensitivity
      syndrome, however subjects with Kennedy's disease have normal virilization,
      although progressive gynaecomastia, testicular atrophy and infertility may occur.
      Androgen receptors are expressed widely in the normal brain, and in the anterior
      horn cells of the spinal cord; however, their role in neuronal tissue is not
      known, nor is it known how the androgen receptor gene mutation causes neuronal
      degeneration. Kennedy's disease is likely to be a 'gain of function' abnormality,
      so that the presence of the receptor with an increased number of glutamines is
      toxic to motor neurons. It is possible that the mutation alters interaction of
      the receptor with other neuronal transcription factors, or neuronotoxicity may
      occur because of a non-specific effect caused by the presence of a protein with a
      large homoglutamine domain. Studies of patients with Kennedy's disease have shown
      that expression of androgen receptor mRNA and protein in spinal cord may be
      decreased, as can be the affinity of the mutant receptor for androgen. In vitro
      studies have shown impaired transcription activation ability of the mutant
      androgen receptor. The age at onset of Kennedy's disease may correlate with the
      size of the CAG repeat, however there is a large degree of variability of age at
      onset between subjects with the same number of repeats. Further study of the
      effect of the Kennedy's disease mutation on androgen receptor function in motor
      neurons will allow us to increase our understanding of the pathogenesis of this
      disease.

PMID- 8867072
TI  - Testosterone therapy and the pathogenesis of Kennedy's disease (X-linked
      bulbospinal muscular atrophy).
AB  - The mutation in X-linked bulbospinal muscular atrophy (XBSMA) is an increased CAG
      triplet repeat coding for a polyglutamine domain in the gene for the androgen
      receptor. This might impair the effect of testosterone on motor neurons, leading
      to their progressive degeneration. We report a trial of high-dose oral
      testosterone therapy in two brothers with XBSMA. Patient 1 received 37.5 mg of
      testosterone daily for more than 18 months, and Patient 2 received 25 mg per day
      for six months, both in combination with exercise therapy. Patient 1 showed
      improvement of up to 300% in muscle work output. Patient 2, who did less
      exercise, had no symptomatic improvement. These results indicate that exogenous
      testosterone therapy is not harmful, and may produce functional improvement when
      combined with exercise. We hypothesize that high-dose testosterone may reduce a
      toxic gain of function that the mutation produces, perhaps by inhibiting
      glutamate neurotoxicity.

PMID- 8867073
TI  - Epidemiology of multiple sclerosis in Arabs in Jordan: a comparative study
      between Jordanians and Palestinians.
AB  - In a 2-year hospital-based study in Jordan 131 Arab multiple sclerosis patients
      were identified including 84 Palestinians and 36 Jordanians. Based on MS/ALS case
      ratio, multiple sclerosis was found to be twice as common among Palestinians than
      Jordanians. Other than the less marked female preponderance among Jordanian
      patients, the disease had the same clinical and paraclinical characteristics in
      both groups. It was more likely for Palestinian and Jordanian patients to
      originate from the northern parts of their countries, to be Rh negative and to be
      HLA-DR2 positive than their controls. Palestinians (patients and controls) did
      not show significant differences from Jordanians (patients and controls) in
      relation to their eye color, ABO and Rh blood groups distribution nor the HLA-DR
      or HLA-DQ (apart from HLA-DQ3) epitopes frequency, thus not offering any
      significant difference in the genetic-racial markers studies to explain the
      difference in the observed disease susceptibility. Previous studies demonstrated
      that 2 racially different populations sharing the same environment can have
      different risk of developing multiple sclerosis, but this study has shown that
      this can also be true for 2 racially similar populations sharing the same
      environment.

PMID- 8867074
TI  - Quantitative evaluation of normal muscle tone.
AB  - Forty-eight normal subjects were evaluated for the purpose of objectively
      quantifying muscle tone. Flexor carpi radialis and extensor digitorum communis
      electromyographic (EMG) activity was simultaneously recorded during wrist
      movements imposed by a torque motor. Each session was subdivided into three
      steps: (1) measurement of the 'intrinsic stiffness index' (ISI) at 10 degrees/s;
      (2) measurement of the 'total stiffness index' (TSI) at 500 degrees/s; (3)
      evaluation of the stretch reflex threshold speed (SRTS). No stretch reflex (SR)
      was found in about half of the subjects, even at the highest speed. ISI was
      higher in males (p < 0.001); significant differences in TSI were found between
      subjects with SR and those without (p < 0.02); no statistical differences in SRTS
      were found for either age or gender. ISI, TSI and SRTS, appear to be reliable
      indices of the range of normal muscle tone for its quantitative assessment.

PMID- 8867075
TI  - HLA class I genotypes in Leber's hereditary optic neuropathy.
AB  - There is evidence that mitochondrial DNA (mtDNA) encoded peptides can restrict
      the immune response in rodents and that these peptides are presented by classical
      and 'neoclassical' class I major histocompatibility complex (MHC) molecules. We
      investigated the frequency of HLA-A and two HLA-B genotypes in index cases of 77
      families with Leber's hereditary optic neuropathy (LHON), on the basis that there
      may be an autoimmune component to this disease. There was no association between
      LHON and any genotype. We conclude that the classical class I MHC loci are not
      major determinants of the development of blindness in LHON.

PMID- 8867076
TI  - Leber's hereditary optic neuropathy with the 11 778 mtDNA mutation and white
      matter disease resembling multiple sclerosis: clinical, MRI and MRS findings.
AB  - A mother and her son are reported who suffer from Leber's hereditary optic
      neuropathy (LHON) with the 11778 mtDNA mutation. In both subjects additional
      clinical and paraclinical evidence of a cerebral demyelinating disease was found.
      This combination has been reported incidentally in females, rarely in males.
      Magnetic resonance imaging and proton spectroscopy findings are reported. These
      findings are compatible with multiple sclerosis.

PMID- 8867077
TI  - An amyloid protein in familial cerebral amyloid angiopathy (British type)

PMID- 8867078
TI  - Humoral response to the human heat shock 60 kDa protein in myasthenia gravis.

PMID- 8867079
TI  - The autonomic nervous system and hypoxia: mountain medicine.

PMID- 8867080
TI  - Prejunctional regulation of reserpine-resistant sympathetic vasoconstriction and
      release of neuropeptide Y in the pig.
AB  - The prejunctional regulation of non-adrenergic sympathetic vasoconstriction and
      release of neuropeptide Y (NPY) was investigated in vivo. In reserpinized pigs
      (with depleted noradrenaline (NA)), it was demonstrated that brief sympathetic
      nerve stimulation (2 pulses of 20 Hz) of the spleen, kidney and hind limb in the
      presence of the alpha 2-adrenoceptor agonist UK 14,304 (1 micrograms/kg per min
      i.v.) evoked reproducible vasoconstrictor responses which were reduced by 40-80%
      in comparison to that in the absence of UK 14,304. In addition, the splenic
      overflow of NPY-like immunoreactivity (-LI) was reduced. After cessation of the
      UK 14,304 infusion all these effects were reversed by addition of the alpha 2
      adrenoceptor antagonist yohimbine (0.2 mg/kg i.v.). Also the Y2 receptor agonist
      NPY(13-36) reduced the splenic overflow of NPY-LI. Splenic vasoconstriction per
      se was evoked by another Y2 receptor agonist N-acetyl[Leu28Leu31]NPY(24-36),
      while no vascular effects in the kidney or hind limb were observed. Both Y2
      agonists displaced [125I]NPY binding to splenic membranes with higher potency
      than the Y1-receptor agonist [Leu31Pro34]NPY(1-36). No evidence was obtained for
      angiotensin II mechanisms being important for the enhanced NPY release after
      reserpine in spite of elevated renin release. The present results show that in
      the absence of NA, repetition of brief sympathetic nerve stimulation evokes
      vascular effects and NPY-LI release which are repeatable and these effects are
      efficiently modulated via alpha 2-adrenoceptors. Furthermore, the Y2 receptors
      may mediate both prejunctional inhibition of NPY release, as well as
      postjunctional vasoconstrictor effects in the pig spleen.

PMID- 8867081
TI  - Stimulatory role of the dorsal motor nucleus of the vagus in gastrointestinal
      motility through myoelectromechanical coordination in cats.
AB  - This study was undertaken to investigate the effect of stimulation of the dorsal
      motor nucleus of the vagus (DMV) on myoelectric activity and motility of the
      gastric antrum and duodenum in normal and in vagotomized cats. 37 cats were
      starved for 24 h and then anesthetized with alpha-chloralose (70-80 mg/kg, iv).
      Electrical stimulation (0.1 mA, 0.2 ms, 50 Hz) of the left DMV was performed
      through a stereotaxically inserted electrode in 19 of the cats. The remaining 18
      cats were injected in the left DMV with a glutamate solution (1 M, 200 nl)
      through an inserted 3-barreled micropipette. The myoelectric activity (slow wave)
      and the motility of the gastric antrum (2 cm proximal to the pylorus) and
      duodenum (3 cm distal to the pylorus) were measured using serosal bipolar
      electrodes and intraluminal balloons. Both the electrical and the glutamate
      stimulations of the DMV markedly increased the occurrence of spike potentials on
      the antral and duodenal myoelectric activity; however, the stimulations
      significantly decreased the frequency of the antral slow wave. The stimulations
      also produced increases in the motility of the antrum and duodenum which
      corresponded to the changes in the myoelectric activity. All the changes in the
      myoelectric activity and the motility were not observed after the ipsilateral
      vagotomy. Thus, these results strongly suggest that the dorsal motor nucleus of
      the vagus has a stimulatory influence on antral and duodenal motility through
      myoelectromechanical coordination via the vagus nerve in cats.

PMID- 8867082
TI  - Development and segmental organization of rostrocaudal dendrites of rat
      sympathetic preganglionic neurons.
AB  - The longitudinal organization of preganglionic sympathetic neurons in the adult
      mammalian spinal cord takes the general form of a ladder. In the rat, the
      preganglionic neurons of the intermediolateral cell column (IML) have extensive
      dendritic arborizations in both rostrocaudal and mediolateral directions. We have
      studied the development of the rostrocaudal dendritic projection by retrogradely
      labeling single sympathetic preganglionic spinal segments with the membrane label
      DiI. The rostrocaudal dendrites of sympathetic preganglionic neurons in the IML
      begin to develop prenatally on embryonic day 19-20 (E19/20), several days after
      these neurons develop mediolaterally oriented dendrites. Between E19 and
      postnatal day 1 (P1), the rostrocaudal dendrites attain a length of approx. 200
      microns. As the rostrocaudal dendrites elongate, the preganglionic neurons form
      distinct clusters between which dendritic bundles are seen. Following a growth
      spurt from E19 to P1, the average rostrocaudal dendritic length approximates
      twice the distance between clusters from P1 to P9.

PMID- 8867083
TI  - Radioligand binding and autoradiographic visualization of adenosine transport
      sites in human inferior vagal ganglia and their axonal transport along rat vagal
      afferent neurons.
AB  - The present study has employed membrane-binding studies and in vitro
      autoradiography to demonstrate the presence of adenosine transport sites in human
      inferior vagal ganglia using [3H]nitrobenzylthioinosine ([3H]NBMPR), a potent
      inhibitor of adenosine transport. In addition, [3H]NBMPR was used to determine
      whether adenosine transport sites are subject to axonal transport along the rat
      vagus nerve. Binding of [3H]NBMPR to human inferior vagal ganglia membranes was
      saturable and reversible. Saturation experiments revealed a single class of high
      affinity-binding sites with a Kd of 93.73 +/- 23.13 pM and Bmax of 413.50 +/-
      50.40 fmol/mg protein. In displacement experiments, the adenosine transport
      inhibitor dipyridamole was the most potent displacer of [3H]NBMPR binding (Ki =
      42.7 +/- 28.0 nM). Adenosine itself was able to fully displace [3H]NBMPR binding
      with a Ki of 115.0 +/- 34.0 microM. The A1/A2a adenosine receptor agonist 5'-(N
      ethylcarboxamido)-adenosine (NECA) was able to fully displace [3H]NBMPR binding
      in only one experiment at a concentration of 100 microM, yielding an affinity
      1000-fold higher than its affinity for adenosine receptors. All competition
      curves obtained from displacement experiments displayed monophasic profiles,
      indicating the presence of a single class of [3H]NBMPR binding sites. Incubation
      of human inferior vagal ganglia sections with [3H]NBMPR (0.7 nM) revealed dense
      binding which appeared to be consistent with the distribution of neuronal cell
      bodies in this tissue. Following unilateral ligation of the vagus nerve in the
      rat, accumulation of [3H]NBMPR binding sites occurred both proximal and distal to
      the vagal ligatures. These results suggest that [3H]NBMPR binds with high
      affinity to a single class of adenosine transport sites, and that these sites are
      present on vagal afferent neurons in the human and undergo bidirectional axonal
      transport along the rat vagus nerve.

PMID- 8867084
TI  - Intracerebroventricular injection of methylatropine suppresses insulin response
      to oral glucose load in rats.
AB  - Hepatic glucoreceptor-vagal afferent inputs to the central nervous system and
      pancreatic vagal efferent stimuli are important for insulin secretion. In the
      present study, we examined the effect of intracerebroventricular (i.c.v.)
      injection of atropine methyl bromide (methylatropine) on the insulin response
      following glucose ingestion in rats. When rats were injected with methylatropine
      i.c.v., the plasma glucose concentration increased, the insulin response reduced,
      and glucagon-like peptide-1 (7-36) amide (tGLP-1) was unchanged following an oral
      glucose load, compared with the controls. The plasma insulin response following
      an intravenous glucose load was not affected by i.c.v. or intraperitoneal
      injection of methylatropine. A transient increase in plasma insulin after
      selective hepatic vagotomy was inhibited by i.c.v. injection of methylatropine.
      Arterial blood pressure or pulse rate was not changed by i.c.v. injection of
      methylatropine. These results show that the central nervous system plays an
      important role in the vagal control of the insulin response to glucose ingestion.
      In rats, for the insulin response soon after glucose ingestion (early phase
      insulin response), direct neural control (hepatic vagal afferent-central nervous
      system-pancreatic vagal efferent) of the islet B cells seems more important than
      the intestinal insulinotropic hormone, tGLP-1.

PMID- 8867085
TI  - Central connections of the motor and sensory vagal systems innervating the
      trachea.
AB  - Cholera toxin beta-subunit was used as both a transganglionic and retrograde cell
      body tracer to determine respectively the central sensory and motor systems
      innervating the trachea in three mammalian species, dog, ferret and rat. A basic
      pattern was found in all three animals. Sensory fibers terminated in three
      subnuclei of the nucleus tractus solitarius (NTS) with the densest concentration
      localized in a restricted part of the medial part of the rostral NTS. Weaker
      projections were identified in the ventrolateral NTS subnucleus and sparse
      labeling was seen in the commissural NTS subnucleus. No labeling was identified
      in the area postrema. The pattern of retrograde cell-body labeling was also
      similar in all three species. Two main sites were labeled: the rostralmost part
      of the dorsal vagal nucleus and the rostral nucleus ambiguus (NA). In the NA,
      cell labeling was found in mainly in the ventral (or external) portion of the
      nucleus, but some labeled neurons were consistently found in the compact NA as
      well. In addition, labeled neurons were also seen in the dorsomedial part of the
      C1-C2 ventral horn. In summary, the central sites of termination of the sensory
      fibers and cells of origin innervating the trachea were similar in all three
      species.

PMID- 8867086
TI  - Intravenously-injected naloxone reverses the decrease in renal sympathetic nerve
      activity seen during hypotensive hemorrhage in conscious rabbits by acting
      through central mechanisms.
AB  - The response of renal sympathetic nerve activity (RNA) to hemorrhage was examined
      in chronically-instrumented conscious rabbits. Hemorrhage was induced at a rate
      of 5 ml/kg per min until the mean arterial pressure fell below 40 mmHg. The mean
      arterial pressure then remained at around 80 mmHg until 10 ml/kg of hemorrhage
      (normotensive hemorrhage) before falling to below the pre-hemorrhagic control
      level (hypotensive hemorrhage). The RNA response showed a biphasic pattern, i.e.,
      it increased during normotensive hemorrhage, then fell below the control level
      during hypotensive hemorrhage. To examine the mechanism involved in this decrease
      in RNA, naloxone (7.5 mumol/kg), an opioidergic receptor antagonist, was
      intravenously injected 1 min after the end of hemorrhage. Intravenous injection
      of naloxone caused an increase in mean arterial pressure and RNA to the level
      seen during normotensive hemorrhage. These results indicate that the decrease in
      RNA induced by hypotensive hemorrhage is mediated by opioidergic receptors. To
      determine whether the effects of naloxone are mediated via central or peripheral
      opioidergic receptors, naloxone was replaced by an equimolar solution of
      methylnaloxone, a form unable to cross the blood-brain barrier. Neither the mean
      arterial pressure nor RNA was significantly altered by administration of methyl
      naloxone. These results suggest that the effects of naloxone on both the RNA and
      the mean arterial pressure are mediated via central opioidergic receptors, i.e.,
      the sympathoinhibition induced by hypotensive hemorrhage is mediated via the
      stimulation of central opioidergic receptors.

PMID- 8867087
TI  - Asymmetry and time-course of cutaneous sympathetic reflex responses following
      sustained excitation of chemosensitive nociceptors in humans.
AB  - Sympathetic reflex responses were elicited in human volunteers by sustained
      selective excitation of nociceptors by noxious chemicals, namely topical
      application of mustard oil which elicited burning pain, or histamine which
      induced itching in a skin area of 5 cm2 on the volar aspect of one forearm.
      Stimulus-related sympathetic reflex responses were studied by means of computer
      assisted infrared thermography of the palmar aspects of both hands. Nociceptive
      stimulation induced a decrease of skin surface temperature in both hands
      interpreted as vasoconstriction. The magnitude of the reflex cooling was
      correlated with the magnitude of the sensation (r = 0.49), but independent of the
      quality of sensation (itch or pain). The temperature reduction was maintained for
      more than 30 min and its time-course matched the time-courses of pain or itch
      sensations. It is concluded that the sustained and selective excitation of
      nociceptors elicits a sustained sympathetic reflex response, which adapts very
      slowly. The time-course of the reflexes suggests that these are not arousal
      responses, but may be indicators of nociceptive processing in conscious humans.
      Contralateral temperature decreases were consistently smaller than ipsilateral
      ones. Thus, sustained nociceptive-specific vasoconstrictor reflexes may be
      somatotopically organised with an emphasis on areas close to the painful stimulus
      (homotopic), which has so far only been shown in animals. The study thus
      demonstrates for the first time in humans the presence of a sympathetic reflex
      asymmetry, which is specific for nociceptive afferent input.

PMID- 8867088
TI  - Inhibition of nitric oxide production during electrical stimulation of the nerves
      supplying the rat knee joint.
AB  - A role for nitric oxide in the regulation of knee joint blood flow in the male
      anaesthetised rat was investigated using laser Doppler perfusion imaging.
      Intravenous infusion of the nitric oxide synthase inhibitor N omega-nitro-L
      arginine methyl ester (L-NAME) at a rate of 0.1 and 1 mg/kg per h caused an
      initial, but transient, rise in vascular resistance by about 15%. Mean arterial
      blood pressure was by and large unaffected by both dose of inhibitor during these
      first 5 min of infusion. The effect of an alternative nitric oxide synthase
      inhibitor NG-monomethyl-L-arginine (L-NMMA) was also investigated. When 10 mg/kg
      per h of this drug was infused intravenously, there was a negligible effect on
      joint vascular resistance for the first 40 min but it then fell by about 15% over
      the next 20 min of infusion; mean arterial pressure gradually rose throughout
      administration. Electrical stimulation of the saphenous nerve in control animals
      elicited a frequency-dependent constriction of articular blood vessels over the
      range 5-30 Hz. Nerve stimulation at lower frequencies had little effect on joint
      capsular perfusion. When the nerve was stimulated over the same range of
      frequencies but in the presence of L-NAME it was found that the frequency
      response profile was unaffected. However, intravenous infusion of the less potent
      inhibitor L-NMMA caused a greater vasoconstrictor response to nerve stimulation
      over all but the lowest frequency tested. The results of these experiments
      indicate that endogenous nitric oxide may be produced in only very small amounts
      by the vascular bed of the rat knee joint. This differs markedly from the
      findings of a previous study in the rabbit knee joint where L-NAME administration
      resulted in a large and sustained increase in vascular resistance, suggesting
      substantial and continuous NO release. A unique isoform of the enzyme may
      possibly occur in the terminals of the nerves supplying the joint whose enzymatic
      activity is only inhibited by L-NMMA and not L-NAME.

PMID- 8867089
TI  - 5-Hydroxytryptamine depolarizes neurons of cat pancreatic ganglia.
AB  - Pancreatic ganglia contain 5-hydroxytryptamine (5-HT)-immunoreactive axons, some
      of which are extensions of myenteric neurons located in the pyloric antrum and
      proximal duodenum. The present study investigated the effect of 5-HT on the
      membrane potential of cat pancreatic ganglion neurons by means of intracellular
      recordings in vitro. Pressure application of 5-HT evoked a fast depolarization in
      29 of 147 neurons and a slow depolarization in 89 of 147 neurons. A biphasic
      response was observed in 10 of 108 neurons. The 5-HT-induced slow depolarizing
      response was not altered in a low Ca2+ (0.1 mM), high Mg2+ (15 mM) solution nor
      by hexamethonium (10(-4) M) or atropine (10(-6) M). The fast depolarizing
      response was associated with a decrease of membrane input resistance (-17.2%).
      The slow depolarizing response was associated with either a decrease (-19.6%) in
      24, an increase (+25.0%) in 20, or without a detectable change of membrane input
      resistance in 10 out of 54 neurons tested. Conditioning hyperpolarization
      increased the amplitude of both fast and slow depolarizing responses. A low Na+
      (68.5 mM) solution and a high K+ (23.5 mM) solution significantly reduced the
      amplitude of the slow depolarizing response. A low Cl- (9.6 mM) solution had no
      significant effect on the slow depolarization. The 5-HT3 receptor antagonist MDL
      72222 (Bemesetron) blocked the 5-HT-evoked fast depolarizing response. BRL 24924
      (Renzapride) and 5 HT-DP, antagonists for the putative 5-HT1P receptor, blocked
      the slow depolarizing response. The 5-HT3 receptor agonist 2-methyl-5-HT evoked a
      fast depolarizing response and MCPP, an agonist for the putative 5-HT1P receptor,
      evoked a slow depolarizing response. Spiperone (a 5-HT1A receptor antagonist) and
      mianserin (a 5-HT2 receptor antagonist) had no effect on either depolarizing
      response to 5-HT. The results show that pancreatic ganglion neurons responded to
      5-HT with fast and slow depolarizing responses. The data suggest that these
      responses were mediated by the 5-HT3 receptor and the putative 5-HT1P receptor,
      respectively.

PMID- 8867090
TI  - Excitation of rat sympathetic preganglionic neurones by selective activation of
      the NK1 receptor.
AB  - Whole-cell current clamp recordings were made from 32 identified sympathetic
      preganglionic neurones (SPN) in neonatal rat thoracolumbar spinal cord slices.
      Perfusion of substance P (SP; 0.1-10 microM) depolarised 7 out of 15 neurones
      tested and the selective NK1 receptor agonist GR73632 (0.075-5 microM)
      depolarised 14 out of 24 neurones. The response to GR73632 could be maintained in
      the presence of tetrodotoxin (0.25-0.5 microM; n = 3) and was irreversibly
      reduced or abolished by the selective NK1-receptor antagonist CP-99,994 (1-3
      microM; n = 3). In 3 neurones, GR73632 evoked both a depolarising response and
      inhibitory postsynaptic potentials (IPSPs) and in the one neurone tested, the
      IPSPs were blocked by strychnine (20 microM), suggesting that NK1 receptors may
      also be found upon inhibitory glycinergic interneurones. The application of
      either GR73632 or SP to a subpopulation of previously quiescent SPN evoked
      rhythmical oscillations in membrane potential (n = 6). These results indicate
      that the NK1 receptor may play an important role in the regulation of both SPN
      and of inhibitory interneurones presynaptic to SPN.

PMID- 8867091
TI  - Differences in the responses to purinergic nerve stimulation and applied ATP in
      the guinea-pig vas deferens.
AB  - The responses to sympathetic nerve stimulation and to applied ATP in the guinea
      pig vas deferens were compared. Nifedipine (10 microM) markedly reduced the non
      adrenergic neural contraction but only partially blocked the contractions
      produced by bath-applied ATP. Suramin (300 microM) also markedly reduced the
      contractile responses produced by nerve stimulation, but had no significant
      effect on the contractions produced by bath-applied ATP. Using intracellular
      recording techniques, nerve stimulation was shown to produce an excitatory
      junction potential which was abolished by suramin (1 microM). Ionophoretic
      application of ATP and bath-applied ATP also produced a depolarization. Suramin
      (1 microM) failed to abolish the response to bath-applied ATP and enhanced the
      ionophoretically induced depolarization. These results suggest either that ATP is
      not a transmitter in the vas deferens or that two classes of purinoceptor are
      present, one suramin-sensitive receptor which produces a contraction via the
      opening of voltage-dependent Ca2+ channels, and another which is suramin
      resistant and produces a contraction by another means.

PMID- 8867092
TI  - Depressed baroreflex in heart failure is not due to structural change in carotid
      sinus nerve fibers.
AB  - It is well known that the baroreceptor reflex is blunted in the heart failure
      state. However, the mechanisms for this depression are not well understood. The
      aim of the present study was to determine if carotid sinus nerve fiber density is
      decreased in the heart failure state. Experiments were carried out in pacing
      induced heart failure and normal dogs. The carotid sinus nerve (CSN) was
      dissected and the CSN discharge responses to changes in arterial pressure with
      nitroglycerin (25 micrograms/kg, i.v.) or phenylephrine (10 micrograms/kg, i.v.)
      were recorded. Thereafter, the carotid sinus area was isolated and perfused with
      oxygenated Krebs-Henseleit solution. Carotid sinus baroreceptor single-unit
      activity was recorded and a carotid sinus pressure-discharge curve was
      constructed using either static or pulsatile pressure. Finally, the carotid sinus
      nerve was removed and fixed at its in situ length in 3% glutaraldehyde. The fixed
      carotid sinus nerve was cut transversely in 0.5-1.0-micron sections and prepared
      for electron microscopy. A photographic collage of the CSN was then analyzed at
      4000 x magnification. The total number, diameter and area of myelinated and non
      myelinated fibers were measured with a digitizer and the density and diameter
      distribution were calculated. Carotid sinus nerve discharge responses to change
      in arterial pressure were significantly blunted in dogs with pacing-induced heart
      failure. Furthermore, single-unit baroreceptor responses to both static and
      pulsatile pressurization were markedly depressed in dogs with heart failure.
      However, there was no change in either fiber density or the ratio of myelinated
      fibers to unmyelinated fibers in the carotid sinus nerve in heart failure. In
      addition, there was no change in the distribution of either fiber diameter or
      cross-sectional area in the carotid sinus nerve in dogs with heart failure. These
      data indicate that there is no significant change in the number or type of fibers
      in the CSN of dogs with heart failure. Therefore, the depressed baroreceptor
      reflex in heart failure is not due to structural changes in fibers of the CSN.
      The depressed baroreflex is most likely due to desensitization of individual
      baroreceptors.

PMID- 8867093
TI  - Nonuniform sympathetic nerve responses to intravenous hypertonic saline infusion.
AB  - Peripheral hyperosmolality produced by the intravenous infusion of hypertonic
      saline (HTS) increases mean arterial blood pressure (MAP) in experimental
      animals. The mechanisms mediating the pressor response have not been fully
      ascertained, but likely involve vasopressin and/or activation of the sympathetic
      nervous system. The primary aim of this study was to determine if HTS infusion
      produces regionally uniform or nonuniform changes in sympathetic nerve discharge
      (SND). For this purpose we recorded renal, splanchnic and lumbar SND during
      intravenous HTS infusion (2.5 M NaCl, 10 microliters/100 g BW per min) in
      chloralose-anesthetized, Sprague-Dawley rats. In rats with intact arterial
      baroreceptors, HTS infusion significantly increased MAP (17 +/- 2 mmHg) and
      lumbar SND (29 +/- 13%) but reduced splanchnic (-52 +/- 7%) and renal SND (-33 +/
      8%). After sinoaortic denervation (SAD), HTS infusion significantly increased
      MAP (28 +/- 6 mmHg) and lumbar SND (27 +/- 9%) and decreased renal SND (-22 +/-
      8%). The increase in lumbar SND occurred significantly sooner in SAD compared
      with baroreceptor-intact rats. In contrast, splanchnic SND remained unchanged
      from control levels during HTS infusion after SAD. These results demonstrate that
      HTS infusion produces regionally nonuniform changes in SND, and suggest that the
      pressor and lumbar sympathoexcitatory responses to HTS infusion are opposed by
      the arterial baroreceptors.

PMID- 8867094
TI  - Presence of vasomotor and respiratory rhythms in the discharge of single
      medullary neurons involved in the regulation of cardiovascular system.
AB  - We analyzed the discharges of 77 single neurons located in the rostral
      ventrolateral medulla (RVLM, n = 25), caudal ventrolateral medulla (CVLM, n =
      18), lateral tegmental field (LTF, n = 19) and caudal raphe nuclei (n = 15).
      These recordings were made from 36 vagotomized and sinoaortic denervated cats
      that were either decerebrate (n = 27) or anesthetized with urethane (n = 9) and
      from 3 decerebrate cats with intact sinoartic and vagal nerves. These neurons
      were classified as sympathetic-related (n = 61) if spike triggered averaging
      showed that their naturally occurring discharges were correlated to either the
      cardiac related (2-6 Hz) or a faster (10 Hz) oscillation in inferior cardiac
      sympathetic nerve discharge. Neurons were classified as sympathetic-unrelated (n
      = 16) if they lacked these characteristics. We used autoregressive spectral
      techniques to detect additional slower oscillations hidden in the variability of
      neuronal discharge and possibly correlated to the oscillations of systolic
      arterial pressure (SAP). This analysis revealed the existence of a low frequency
      (LF) oscillation (0.12 +/- 0.02 Hz) in the discharges of 36 sympathetic-related
      and 9 sympathetic-unrelated neurons. In relation to 35 neurons in 21 animals
      there was also an LF component in SAP variability. In 29 instances the LF
      neuronal discharges and SAP variabilities were significantly correlated. In
      addition, there was a high frequency (HF) oscillation (0.34 +/- 0.06 Hz) in the
      discharges of 59 medullary neurons. In 56 cases the HF in neuronal discharge
      variability cohered to that in SAP variability. These data are the first to
      demonstrate the existence of an LF component in the discharges of individual
      medullary neurons, at least some of which were likely to be involved in the
      regulation of the cardiovascular system. Since these oscillations were evident in
      cats with section of sinoaortic and vagal nerves, they likely reflect central
      rhythmogenic properties.

PMID- 8867095
TI  - Can neurons in the nucleus ambiguus selectively regulate cardiac rate and atrio
      ventricular conduction?
AB  - Previous anatomic data have described the distribution of presumptive negative
      chronotropic and negative dromotropic neurons in the ventro-lateral nucleus
      ambiguus (NA-VL) following injections of retrograde tracers into physiologically
      selective parasympathetic intracardiac ganglia. Negative dromotropic neurons were
      preferentially distributed in the rostral NA-VL (rNA-VL). Negative chronotropic
      neurons were preferentially distributed in the caudal NA-VL (cNA-VL). Significant
      numbers of both types of cardio-inhibitory neurons were observed to overlap in an
      intermediate level of the NA-VL (iNA-VL). In the present report, we have examined
      the effects of microinjections of the excitatory amino-acid glutamate (GLU) into
      the cNA-VL and iNA-VL on cardiac rate and AV conduction while recording the
      electrocardiogram in paced and non-paced cat hearts. The data indicate that: (i)
      excitation of neurons in the cNA-VL causes a 58 +/- 17% reduction in cardiac
      rate, without influencing AV conduction; and (ii) excitation of neurons in the
      iNA-VL causes both a reduction in heart rate (68 +/- 12%) and a decrease in the
      rate of AV conduction (38 +/- 7%). These physiological results support the
      anatomical inference that neurons in the cNA-VL that are retrogradely labeled
      from physiologically selective parasympathetic intracardiac ganglia selectively
      exhibit negative chronotropic properties. Furthermore, the data indicate that
      there is a longitudinal cardiotopic organization of both negative chronotropic
      and negative dromotropic neurons in the NA-VL. This CNS organization mirrors the
      peripheral organization of functionally selective cardiac components of the vagus
      nerve. Finally, the data are consistent with the hypothesis that anatomically
      separated and functionally selective parasympathetic preganglionic vagal
      motoneurons in the NA independently control cardiac rate and AV conduction.

PMID- 8867096
TI  - Caffeine antinociception: role of formalin concentration and adenosine A1 and A2
      receptors.
AB  - Caffeine produces antinociception in the formalin test at lower doses than in
      thermal threshold tests. In this study, we examined (a) the effect of formalin
      concentration on the action of caffeine, and (b) the relative involvement of
      adenosine A1 and A2 receptors in the action of caffeine. Formalin 1%, 2% and 5%
      produces a concentration-dependent increase in flinching behaviour in rats. At 5%
      formalin, the EC50 for caffeine in reducing phase 2 responses (16-60 min
      following formalin injection) is 40 mg/kg, but at 2%, this is reduced to 5 mg/kg.
      There is no further shift using 1% formalin. Caffeine has a more pronounced
      effect on phase 2A (16-36 min) than on phase 2, with significant effects being
      observed at lower doses. Both 8-cyclopentyltheophylline (A1 selective) and 3,7
      dimethyl-1-propargylxanthine (A2 selective) produce a dose-related inhibition of
      1.5% formalin flinching behaviours between 1-10 mg/kg. Both agents also produce
      locomotor stimulation over this dose range, but significant effects occur only at
      10 mg/kg. These results indicate that antinociception by caffeine shows a high
      dependence on stimulus intensity. At 1-2% formalin, doses of caffeine that
      produce antinociception are now in the range that corresponds to normal human
      dietary and therapeutic intake levels. Both antinociception and locomotor
      stimulation appear to be dependent on activation of adenosine A1 receptors, as
      effects of 3,7-dimethyl-1-propargylxanthine are observed only at a dose which
      blocks adenosine A1 receptors in addition to A2 receptors.

PMID- 8867097
TI  - The effect of Phoneutria nigriventer (armed spider) venom on arterial blood
      pressure of anaesthetised rats.
AB  - The changes induced in the mean arterial blood pressure of anaesthetised rats
      following the administration of armed spider (Phoneutria nigriventer) venom have
      been investigated. The intravenous injection of Phoneutria nigriventer venom (0.1
      mg/kg) evoked a brief and reversible decrease in the mean arterial blood pressure
      whereas a higher dose of venom (0.3 mg/kg) caused a biphasic response
      characterized by a short-lasting hypotension followed by a sustained and
      prolonged hypertension (40-50 min). These changes were accompanied by
      tachycardia, salivation, fasciculations, defecation and respiratory disturbances.
      Pretreatment of the animals with atropine (10 mg/kg), propranolol (100 mg/kg),
      phenoxybenzamine (100 mg/kg) and indomethacin (4 mg/kg) did not significantly
      affect the mean arterial blood pressure changes induced by Phoneutria nigriventer
      venom. Similarly, the bradykinin B2 receptor antagonist Hoe 140 (D-Arg
      [Hyp3,Thi5,DTic7,Oic8]-bradykinin) (0.6 mg/kg), the PAF receptor antagonist WEB
      2086 (3-(4-(2-chlorophenyl)-9-methyl-6H-thieno-(3,2f) (1,2,4)-triazolo-(4,3-a)
      (1,4)-diazepine-2-yl)-(4-morpholinyl)-1-propanone) (20 mg/kg), the tachykinin NK1
      receptor antagonist SR 140333 ((S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-iso
      propoxyphenyl acetyl) piperidin-3-yl] ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]
      octane, chloride) (0.5 mg/kg), the tachykinin NK2 receptor antagonist SR 48968
      ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophen yl)
      butyl]benzamide) (0.5 mg/kg) and the nitric oxide synthase inhibitor N omega
      nitro-L-arginine methyl ester (10 mg/kg) had no significant effect on the mean
      arterial blood pressure changes induced by Phoneutria nigriventer venom. The
      increase in the blood pressure induced by Phoneutria nigriventer venom was also
      not significantly affected by either the angiotensin II receptor antagonist
      losartan (10 mg/kg) or the endothelin ETA receptor antagonist FR 139317 ((R)2
      [(R)-2-[[1-(hexahydro-1H-azepinyl]carbonyl]amino-4-methyl- pentanoyl]amino-3-[3
      (1-methyl-1H-indoyl)]propionyl] amino-3-(2-pyridyl) propionic acid) (30 mg/kg).
      The ATP-dependent K+ channel antagonist glibenclamide (50 mg/kg) reduced by 40%
      the hypotension induced by Phoneutria nigriventer venom without affecting the
      hypertensive response. Pretreatment of the animals with L-type Ca2+ channel
      antagonists such as verapamil (10-100 micrograms/kg/min), diltiazem (40-120
      micrograms/kg/min) and nifedipine (0.3-10 mg/kg) markedly attenuated the
      hypertension induced by Phoneutria nigriventer venom. Verapamil (30
      micrograms/kg/min) and diltiazem (120 micrograms/kg/min) also promptly reversed
      the established hypertension induced by Phoneutria nigriventer venom when infused
      8 min after venom injection. Our results indicate that the brief decrease of
      blood pressure induced by Phoneutria nigriventer venom is partially due to ATP
      dependent K+ channel activation. The prolonged hypertension seems to result from
      direct Ca2+ entry into vascular and/or cardiac muscles.

PMID- 8867098
TI  - Sensitivity to ischemia of chronically infarcted rat hearts; effects of long-term
      captopril treatment.
AB  - Myocardial infarction induced hypertrophy of non-infarcted myocardium, in
      parallel with interstitial and perivascular fibrosis and a decreased capillary
      density, could increase sensitivity to ischemia. The structural cardiac changes
      can be reversed by long-term captopril treatment. In the present study, ischemic
      sensitivity in relation to cardiac perfusion was studied in isolated, perfused
      hearts of untreated and captopril-treated infarcted rats. In chronically (8
      weeks) infarcted hearts, maximal vasodilation in response to administered
      adenosine and nitroprusside, as well as to endogenously released vasodilators
      during reperfusion, was decreased, suggesting impaired cardiac perfusion.
      Ischemic release of purines and lactate was reduced in infarcted hearts,
      indicating decreased sensitivity to ischemia of the remodeled myocardium.
      Captopril treatment (3-8 weeks post myocardial infarction), which reversed
      hypertrophy without affecting the flow capacity of the coronary vascular bed,
      restored maximal cardiac perfusion. Ischemic ATP breakdown was not affected by
      captopril, whereas lactate release was even further reduced, suggesting
      alterations towards a more aerobic ATP production. These data indicate that
      despite the reduced maximal cardiac perfusion, the remodeled myocardium of
      infarcted hearts is less sensitive to ischemia. Reversal of hypertrophy by
      chronic captopril restored maximal cardiac perfusion and led to a better
      preservation of aerobic ATP production during ischemia.

PMID- 8867099
TI  - Characteristics of vasodilatation induced by acetylcholine and platelet
      activating factor in the rat mesenteric arterial bed.
AB  - We examined the nature of the endothelium-dependent vasodilator effects of
      acetylcholine and platelet-activating factor (PAF) on the perfused mesenteric
      arterial bed of the rat. Acetylcholine-induced concentration-dependent
      vasodilatation of the mesentery was not affected by pretreatment with 10(-4) M NG
      monomethyl-L-arginine (L-NMMA), indomethacin, ouabain, or glibenclamide, whereas
      pretreatment with 10(-5) M oxyhemoglobin, 10(-5) M methylene blue, or 10 mM
      tetraethylammonium shifted the concentration-response curves to the right. PAF
      induced concentration-dependent vasodilatation of the mesentery was inhibited by
      pretreatment with L-NMMA, oxyhemoglobin, or methylene blue, and slightly but
      significantly inhibited by tetraethylammonium, whereas indomethacin,
      glibenclamide, and ouabain had no inhibitory effects. PAF-induced vasodilatation
      of the mesentery was more sensitive to nitric oxide-cyclic GMP pathway inhibitors
      (a combined application of L-NMMA, oxyhemoglobin, and methylene blue) than was
      the vasodilatation induced by acetylcholine. Perfusion of the mesentery
      preparations with acetylcholine or PAF increased the levels of cyclic GMP in the
      effluent. These effects were completely inhibited by L-NMMA or oxyhemoglobin.
      These results suggest that the endothelium-dependent vasodilator effects of PAF
      are primarily mediated by endothelium-derived nitric oxide (NO) and those of
      acetylcholine are mediated by both NO and endothelium-derived hyperpolarizing
      factor (EDHF).

PMID- 8867100
TI  - 5-Hydroxytryptamine-induced Cl- transport is mediated by 5-HT3 and 5-HT4
      receptors in the rat distal colon.
AB  - In the rat distal colon, 5-hydroxytryptamine (5-HT)-induced Cl- secretion is seen
      as a rise in short circuit current (Isc). We investigated the 5-HT receptor
      mediating 5-HT-induced Cl- secretion in the rat distal colon. Rat distal colon
      was prepared either by stripping away the muscularis propria with the neural
      ganglia, or by leaving it intact. The tissue was mounted in Ussing chambers and
      short circuited. 5-HT receptor agonist-induced changes (delta) in Isc were
      recorded in the presence and absence of 5-HT receptor antagonists. In stripped
      preparations, the rank order of potency of agonists was: 5-HT > 5
      methoxytryptamine > alpha-methyl-5-HT >> 2-methyl-5-HT. 5-HT and 5
      methoxytryptamine-induced changes in Isc were antagonized by > or = 0.3 microM
      tropisetron with pA2 values 6.5 and 6.4, respectively. The 5-HT4 antagonist, SC
      53606, antagonized the 5-HT-induced response with a pA2 of 7.2. 5-HT1-like
      (methysergide), 5-HT1P (N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide (5
      HTP-DP)), 5-HT2A (ketanserin) and 5-HT3 (ondansetron) receptor antagonists had no
      significant effect on the 5-HT response in stripped tissue. 3 microM forskolin,
      or 10 microM 3-isobutyl-1-methyl-xanthine (IBMX), decreased the EC50 and
      increased the maximum 5-HT response. The 2-methyl-5-HT and 5-HT-induced delta Isc
      in the unstripped colon preparation were antagonized by the 5-HT3 antagonist,
      ondansetron (0.3 nM), and 2-methyl-5-HT activity was abolished by pretreatment
      with tetrodotoxin. In conclusion, 5-HT-induced delta Isc is neurally mediated via
      a 5-HT3 receptor, and non-neurally mediated via a 5-HT4 receptor in the rat
      distal colon.

PMID- 8867101
TI  - Different mechanisms involved in relaxation of guinea-pig trachea by endothelin-1
      and -3.
AB  - The effects of endothelin-1 and endothelin-3 were investigated on carbachol
      contracted guinea-pig isolated trachea. Endothelin-1 and endothelin-3 (0.1-100
      nM) induced partial dose-dependent relaxation of the precontracted preparations.
      The endothelin-1-induced relaxation was markedly attenuated by haemoglobin (10
      microM) and methylene blue (10 microM) and by epithelium removal. In contrast,
      endothelin-3-induced relaxation was not affected by haemoglobin, methylene blue
      or epithelium removal. The large conductance Ca(2+)-activated K(+)-channel
      blocker, charybdotoxin, antagonized the endothelin-1- and the endothelin-3
      induced relaxation to the same extent. These results show that both endothelin-1
      and endothelin-3 relaxant activities are modulated by charybdotoxin-sensitive
      K(+)-channels, while the nitric oxide pathway is only involved in endothelin-1
      relaxant effects.

PMID- 8867102
TI  - Role of bradykinin B2 receptors and mast cells in the bradykinin-induced skin
      response in the rat.
AB  - We investigated the role of activation of bradykinin receptors and mast cells in
      the microvascular leakage of the vessels of the skin induced by the
      intracutaneous (i.c.) injection of bradykinin in the rat. We evaluated the
      effects of HOE140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2
      receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4H
      benzo[4,5]cyclohepta[1, 2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine
      H1 receptor antagonist with mast cell stabilizing properties, on the skin
      response. Evans blue dye extravasation served as an index of the increase in
      vascular permeability. Bradykinin (2-100 nmol/site i.c.) induced the
      extravasation of Evans blue dye in a dose-dependent manner. Ketotifen (20 mg/kg
      i.p.) significantly inhibited the leakage of dye induced by bradykinin (10
      nmol/site i.c.) by 66.2%, while HOE140 (1 mg/kg i.v.) had no effect. The
      concomitant injection of HOE140 (0.2, 2 nmol/site) and bradykinin (10 nmol/site
      i.c.), also did not significantly reduce the extravasation of dye. We conclude
      that the extravasation of plasma induced by the i.c. injection of bradykinin is
      mediated mainly by stimulation of the skin mast cells, but not by bradykinin B2
      receptors.

PMID- 8867103
TI  - Effect of cisplatin and cis-platinum (II) phosphonate complex on murine mast
      cells.
AB  - We investigated the effect of two cis-platinum (II) complexes, cis-[PtCl2(NH3)2]
      (cisplatin) and cis-[PtCl2(4-pmpe)2] (4-pmpe stands for diethyl 4
      pyridylmethylphosphonate), which was recently synthetized in our laboratory, on
      murine mast cells. We noticed that both tested compounds were able to evoke
      histamine release from murine mast cells. The histamine secretion was dependent
      on the concentration of compound and on the time and temperature of the reaction.
      It was also dependent on metabolic energy (the reaction was diminished in a
      medium without glucose and abolished in the presence of 2-deoxyglucose). The
      results indicate that cis-platinum (II) complexes activate mast cells to secrete
      histamine via a non-cytotoxic, active secretory process.

PMID- 8867104
TI  - Ca(2+)-induced Ca2+ release activates K+ currents by a cyclic GMP-dependent
      mechanism in single gastric smooth muscle cells.
AB  - The participation of sarcoplasmic reticulum Ca2+ release channels in the
      activation of Ca(2+)-sensitive K+ currents (IK(Ca)) by cyclic dibutyryl GMP was
      investigated in smooth muscle cells from the circular layer of guinea-pig gastric
      fundus. All experiments were performed in the presence of 3 microM nicardipine
      into the bath and low Ca2+ buffering capacity of the pipette-filling solution
      (pCa 7.4). Ruthenium red (10 microM) as well as its combination with 10 microM
      heparin abolished the cyclic GMP-induced activation of IK(Ca), while 10 microM
      heparin remained ineffective. Ryanodine (10 microM) and the subsequently added 1
      microM thapsigargin induced a relatively small increase in IK(Ca) amplitudes. The
      addition of 10 microM ryanodine to 1 microM thapsigargin-containing bath solution
      caused a vast increase in IK(Ca). It is hypothesyzed that protein kinase G
      induced vectorial Ca2+ flux from the cell bulk and sarcoplasmic reticulum Ca2+
      stores toward the plasma membrane is realized by a spontaneous Ca(2+)-induced
      Ca2+ release from a superficially situated Ca2+ store.

PMID- 8867105
TI  - Pharmacological comparison between [3H]GR 113808 binding sites and functional 5
      HT4 receptors in neurons.
AB  - 5-HT4 receptors positively coupled to adenylyl cyclase and possessing unique
      pharmacological properties were first described in mouse colliculi neurons using
      functional studies. The recent introduction of a radiolabeled 5-HT4 receptor
      antagonist, [3H]GR 113808 [1-[2-(methylsulphonylamino)ethyl]4-piperidinyl]methyl
      1-methyl-in dole-3 carboxylate] having high specificity and affinity allowed the
      pharmacological comparison between the specific binding sites identified with
      this compound and the functional 5-HT4 receptors in the same preparation, the
      colliculi neurons. We show here that [3H]GR 113808 binding is saturable in this
      preparation and reveals a homogeneous population of sites with a pKd value of 9.5
      +/- 0.2 and a Bmax of 75 +/- 23 fmol/mg protein. Seventeen agonists and six
      antagonists with molecules structurally related either to indoles, benzamides or
      benzimidazolones and previously known as 5-HT4 receptor ligands, were tested for
      their ability to compete with [3H]GR 113808 binding sites and to stimulate or
      inhibit 5-HT-stimulated adenylyl cyclase activity. Highly significant
      correlations were obtained between the affinities of either agonists or
      antagonists for [3H]GR 113808 binding sites and their potencies for functional 5
      HT4 receptors (r = 0.87 and 0.99, respectively). In addition, we also found good
      correlations between the Kd of several 5-HT4 receptor ligands determined in cell
      membranes of mouse colliculi neurons and their Kd determined in previous studies
      in guinea-pig striatum (0.95) and in human caudate (0.97). [3H]GR 113808 binding
      studies demonstrated that the 50% decrease in 5-HT-stimulated cAMP accumulation
      which followed a 5 min exposure period with 5-HT (10 microM) was not accompanied
      by any significant decrease in the number of binding sites. Longer exposure
      periods with 5-HT resulted in a decrease in [3H]GR 113808 binding sites which
      started to be significant after 30 min.

PMID- 8867106
TI  - ML-7 and W-7 facilitate thromboxane A2-mediated Ca2+ mobilization in rabbit
      platelets.
AB  - The effects of 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML
      7), a myosin light chain kinase inhibitor, and (N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide (W-7), a calmodulin antagonist, on thromboxane A2 receptor
      mediated signal transduction were examined in rabbit washed platelets. ML-7 and W
      7 at 10-30 microM slightly potentiated the aggregation induced by a thromboxane
      A2 receptor agonist, 9,11-dideoxy-9 alpha,11 alpha- epoxymethanoprostaglandin F2
      alpha (U46619), in spite of their known inhibitory actions. ML-7 and W-7
      concentration-dependently enhanced U46619-induced phosphoinositide hydrolysis and
      the increase in internal free Ca2+ concentration in the presence or absence of
      external Ca2+. While ML-7 and W-7 inhibited basal GTPase activity, they augmented
      U46619-induced activation of GTPase in a concentration-dependent manner. The
      present results suggest that ML-7 and W-7 enhance thromboxane A2 receptor
      mediated signal transduction at the receptor/G protein coupling, leading to the
      enhancement of phosphoinositide hydrolysis and Ca2+ mobilization, independently
      of the inhibition of myosin light chain kinase or calmodulin.

PMID- 8867107
TI  - Subcellular localization of ryanodine receptors in rat brain.
AB  - Subcellular fractions of rat brain were used to determine the subcellular
      localization of ryanodine receptors. [3H]Ryanodine binding in purified cortical,
      cerebellar and hippocampal synaptosomes was up to 3.6-fold higher compared with
      mitochondrial fractions. The density of sites (Bmax) in hippocampal mossy fiber
      synaptosomes (249 fmol/mg protein) was 3.7-fold greater than in cortical
      synaptosomes (67 fmol/mg protein) and binding affinity was approximately 2-fold
      greater in the former (KD, 6.1 nM) than the latter (KD, 3.1 nM). At single sub
      saturating concentrations of [3H]ryanodine, binding was 1.6-fold higher in mossy
      fibers compared with total hippocampal synaptosomes. [3H]Ryanodine binding sites
      were distributed similarly in subfractions of cortical synaptosomes and
      microsomes from discontinuous sucrose density gradients. An enrichment of sites
      was found in the lightest fractions containing the lowest activities of plasma
      membrane (5'-nucleotidase) and endoplasmic reticulum (glucose 6-phosphatase)
      enzyme markers when data for microsomal and synaptosomal subfractions were
      expressed as activity/binding per mg protein and when data for synaptosomal
      subfractions were expressed as a percentage of total activity/binding in
      collected fractions. Thus, ryanodine receptors appear to be concentrated in
      presynaptic terminals where they may play a major role in neurotransmitter
      release, and appear to be localized either in a specialized endoplasmic reticulum
      subcompartment or a distinct subcellular organelle.

PMID- 8867108
TI  - Antiproliferative effect in rat vascular smooth muscle cells by osthole, isolated
      from Angelica pubescens.
AB  - The antiproliferative effect of osthole on rat vascular smooth muscle cells was
      examined in this study. A number of mitogenic agents, e.g., foetal-calf serum
      (10%, v/v) and platelet-derived growth factor (20 ng/ml), and pharmacological
      agents, e.g., serotonin (10 microM), ionomycin (3 nM), phorbol 12,13-dibutyrate
      (20 nM) and phorbol myristate acetate (200 nM), were used to induce DNA synthesis
      in rat vascular smooth muscle cells; these effects were concentration dependently
      inhibited by osthole and the half-maximal inhibition (IC50) occurred at 13.6 +/-
      1.8, 11.8 +/- 1.3, 7.9 +/- 0.9, 7.1 +/- 0.2, 7.8 +/- 0.2 and 8.6 +/- 0.4 microM,
      respectively. Osthole itself increased the cyclic AMP and cyclic GMP formations
      in a concentration-dependent manner; it synergistically increase cyclic AMP and
      cyclic GMP levels induced by forskolin and sodium nitroprusside, respectively.
      After 48 h deprivation of serum, cells were re-stimulated with serum and the cell
      cycle was observed by flow cytometry; treatment of cells with osthole (100
      microM) caused a block of serum-inducible cell cycle progression at a point
      before the G1-S boundary. The addition of osthole (100 microM) at various times
      after serum addition to serum-deprived cells showed full inhibition of DNA
      synthesis even when added 6 h after serum. The cell cycle progression block was
      gradually lost as the delay from serum to osthole application was increased from
      6 to 18 h. The effect of osthole on serum-stimulated [3H]thymidine incorporation
      into endothelial cells was examined and the IC50 value (158.7 +/- 2.7 microM, n =
      6) was obtained; it exhibited greater potency (12-fold) for vascular smooth
      muscle cells as compared with endothelial cells as an antiproliferative agent.
      These results suggest that osthole is a selective antiproliferative agent in
      vascular smooth muscle cells. The antiproliferative effect occurs at the early G1
      phase of the cell cycle and is due to the increase in cyclic AMP and cyclic GMP
      contents.

PMID- 8867109
TI  - Blocking effects of otilonium on Ca2+ channels and secretion in rat chromaffin
      cells.
AB  - We describe here the effects of otilonium bromide (an anticholinergic agent
      widely used as an intestinal spasmolytic) on whole-cell currents through Ca2+
      channels (IBa) and catecholamine secretion in rat adrenal glands and isolated rat
      chromaffin cells. Otilonium blocked the peak IBa current in voltage-clamped
      chromaffin cells in a concentration-dependent manner; the IC50 to block IBa was
      4.7 microM. Blockade was not accompanied by a significant shift in the I-V
      relationship for IBa, suggesting that such blockade was not affecting a specific
      subtype of Ca2+ channel. When given intracellularly through the patch pipette,
      otilonium (10 microM) did not block IBa. However, its external application to the
      same cell (10 microM) reversibly reduced IBa by 70%. Otilonium caused a
      concentration-dependent blockade of catecholamine release from perfused rat
      adrenal glands intermittently stimulated with methacholine, high K+ or histamine.
      The IC50 to block secretion after a 5 min incubation with otilonium was 0.02, 0.7
      and 3 microM, respectively, for methacholine, K+ and histamine. The blocking
      effects of otilonium were fully reversible at concentrations below 10 microM. The
      Ca2+ channel agonist Bay K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2
      trifluoromethylphenyl)-pyr idine-5- carboxylate) partially antagonized the
      effects of otilonium on K(+)-evoked secretion and accelerated the time course of
      recovery from inhibition. The results are compatible with the idea that otilonium
      blocks Ca2+ entry into chromaffin cells by blocking voltage-dependent Ca2+
      channels. This would lead to a limitation in the rise in cytosolic Ca2+ at
      secretory sites and to inhibition of catecholamine release in response to
      stimulation of chromaffin cells.

PMID- 8867110
TI  - Neural network based on the input organization of an identified neuron signaling
      impending collision.
AB  - 1. We describe a four-layered neural network (Fig. 1), based on the input
      organization of a collision signaling neuron in the visual system of the locust,
      the lobula giant movement detector (LGMD). The 250 photoreceptors ("P" units) in
      layer 1 are excited by any change in illumination, generated when an image edge
      passes over them. Layers 2 and 3 incorporate both excitatory and inhibitory
      interactions, and layer 4 consists of a single output element, equivalent to the
      locust LGMD. 2. The output element of the neural network, the "LGMD", responds
      directionally when challenged with approaching versus receding objects,
      preferring approaching objects (Figs. 2-4). The time course and shape of the
      "LGMD" response matches that of the LGMD (Fig. 4). Directionality is maintained
      with objects of various sizes and approach velocities. The network is tuned to
      direct approach (Fig. 5). The "LGMD" shows no directional selectivity for
      translatory motion at a constant velocity across the "eye", but its response
      increases with edge velocity (Figs. 6 and 9). 3. The critical image cues for a
      selective response to object approach by the "LGMD" are edges that change in
      extent or in velocity as they move (Fig. 7). Lateral inhibition is crucial to the
      selectivity of the "LGMD" and the selective response is abolished or else much
      reduced if lateral inhibition is taken out of the network (Fig. 7). We conclude
      that lateral inhibition in the neuronal network for the locust LGMD also
      underlies the experimentally observed critical image cues for its directional
      response. 4. Lateral inhibition shapes the velocity tuning of the network for
      objects moving in the X and Y directions without approaching the eye (see Fig.
      1). As an edge moves over the eye at a constant velocity, a race occurs between
      the excitation that is caused by edge movement and which passes down the network
      and the inhibition that passes laterally. Excitation must win this race for units
      in layer 3 to reach threshold (Fig. 8). The faster the edge moves over the eye
      the more units in layer 3 reach threshold and pass excitation on to the "LGMD"
      (Fig. 9). 5. Lateral inhibition shapes the tuning of the network for objects
      moving in the Z direction, toward or away from the eye (see Fig. 1). As an object
      approaches the eye there is a buildup of excitation in the "LGMD" throughout the
      movement whereas the response to object recession is often brief, particularly
      for high velocities. During object motion, a critical race occurs between
      excitation passing down the network and inhibition directed laterally, excitation
      must win this race for the rapid buildup in excitation in the "LGMD" as seen in
      the final stages of object approach (Figs. 10-12). The buildup is eliminated if,
      during object approach, excitation cannot win this race (as happens when the
      spread of inhibition laterally takes < 1 ms Fig. 13, D and E). Taking all lateral
      inhibition away increases the "LGMD" response to object approach, but overall
      directional selectivity is reduced as there is also a lot of residual network
      excitation following object recession (Fig. 13B). 6. Directional selectivity for
      rapidly approaching objects is further enhanced at the level of the "LGMD" by the
      timing of a feed-forward, inhibitory loop onto the "LGMD", activated when a large
      number of receptor units are excited in a short time. The inhibitory loop is
      activated at the end of object approach, truncating the excitatory "LGMD"
      response after approach has ceased, but at the initiation of object recession
      (*Fig. 2, 3, and 13). Eliminating the feed-forward, inhibitory loop prolongs the
      "LGMD" response to both receding and approaching objects (Fig. 13F).

PMID- 8867111
TI  - Intracellular characterization of neurons in the locust brain signaling impending
      collision.
AB  - 1. In response to a rapidly approaching object, intracellular recordings show
      that excitation in the locust lobula giant movement detecting (LGMD) neuron
      builds up exponentially, particularly during the final stages of object approach.
      After the cessation of object motion, inhibitory potentials in the LGMD then help
      to terminate this excitation. Excitation in the LGMD follows object recession
      with a short, constant latency but is cut back rapidly by hyperpolarizing
      potentials. The timing of these hyperpolarizing potentials in the LGMD is
      variable, and their latency following object recession is shortest with the
      highest velocities of motion simulated. The hyperpolarizing potentials last from
      50-300 ms and are often followed by re-excitation. The observed
      hyperpolarizations of the LGMD can occur without any preceding excitation and are
      accompanied by a measurable conductance increase. The hyperpolarizations are
      likely to be inhibitory postsynaptic potentials (PSPs). The behavior of the
      intracellularly recorded inhibitory PSPs (IPSPs) closely parallels that of the
      feed forward inhibitory loop in the neural network described by Rind and
      Bramwell. 2. The preference of the LGMD for approaching versus receding objects
      remains over a wide range of starting and finishing distances. The response to
      object approach, measured both as membrane potential and spike rate, remains
      single peaked with starting distances of between 200 and 2,100 mm, and approach
      speeds of 0.5-2 m/s. These results confirm the behavior predicted by the neural
      network described by Rind and Bramwell but contradicts the findings of Rind and
      Simmons, forcing a re-evaluation of the suitability of some of the mechanical
      visual stimuli used in that study. 3. For depolarization of the LGMD neuron to be
      maintained or increased throughout the motion of image edges, the edges must move
      with increasing velocity over the eye. Membrane potential declines before the end
      of edge motion with constant velocities of edge motion. 4. A second identified
      neuron, the LGMD2 also is shown to respond directionally to approaching objects.
      In both the LGMD and LGMD2 neurons, postsynaptic inhibition shapes the
      directional response to object motion.

PMID- 8867112
TI  - Impulse responses distinguish two classes of directional motion-sensitive neurons
      in the nucleus of the optic tract.
AB  - 1. Recordings were made from direction-selective neurons in the nucleus of the
      optic tract (NOT) and dorsal terminal nucleus (DTN) of the wallaby, Macropus
      eugenii. Responses were elicited in the cells by brief displacements of a wide
      field sine wave grating pattern in their preferred and antipreferred directions.
      The grating pattern was moved by a quarter cycle or less during the experiments.
      Once the stimulus duration was less than a certain value, referred to as the
      integration time, the magnitude of the responses depended on the size of the
      displacement, regardless of the velocity of the movement. The responses elicited
      by movements of the image in less than the integration times are referred to as
      velocity impulse responses. 2. The NOT-DTN contains two kinds of direction
      selective neurons. The cells of the first type were maximally sensitive to
      patterns moving at low velocities (slow cells). These neurons had integration
      times of 40-80 ms. The cells of the second type were most sensitive to stimulus
      movements at high velocities (fast cells) and had integration times of 20-40 ms.
      3. The velocity impulse responses of the slow cells were characterized by a rapid
      increase in firing rate followed by a slow exponential decline over a period of 1
      4 s back to their resting activities. The impulse responses of the fast cells
      showed a rapid increase in firing rate followed by a short-lived inhibition of
      the background activity. 4. When the duration of the moving stimulus was longer
      than the integration times of the cells, they began to resolve the time course of
      the stimulus velocity. Under these conditions the slow cells showed a slow rise
      in firing rate during stimulation and a slow, exponential decay in firing after
      the stimulus came to rest. The fast cells showed a rapid increase in firing rate
      followed by a slow decay during the period of motion and then a short-lived
      inhibitory phase after the motion stopped. 5. The responses to rectangular pulses
      of stimulus velocity could be predicted for both cell types by convolving the
      velocity impulse responses of the cells with the velocity profile of the
      stimulus. Thus the cells responded linearly to image displacement in the sense
      that their responses to the velocity pulses could be described as the sum of a
      set of velocity impulse responses each weighted by the instantaneous stimulus
      strength, the latter being governed by the size of the image displacement. 6.
      Given the demonstration of linearity with respect to image displacement as the
      input, the Fourier transforms of the impulse responses were calculated to reveal
      the temporal filtering characteristics of the neurons. The slow cells had low
      pass characteristics, the main power in the responses being at frequencies below
      5-10 Hz. The fast cells had band-pass temporal filtering properties, the optimum
      pass band being at 6-12 Hz. 7. The filtering properties of the two cell types
      complement each other such that the optokinetic system as a whole is able to
      operate accurately over a wide frequency range.

PMID- 8867113
TI  - Relation between rise times and amplitudes of GABAergic postsynaptic currents.
AB  - 1. We recorded rise times and amplitudes of spontaneous GABAergic inhibitory
      postsynaptic currents (IPSCs) in melanotropes of Xenopus laevis. Average rise
      times did not vary with amplitude, but the rise times of larger IPSCs were less
      variable. A simple linear one-step Markov model for channel opening following the
      binding of a transmitter molecule can quantitatively account for the average rise
      time and its coefficient of variation as a function of amplitude. Our results
      indicate that the observed variations in the rise times are not due to variations
      in transmitter concentrations, but result from stochastic variations in the
      opening of the receptor channels.

PMID- 8867114
TI  - Errors in the control of joint rotations associated with inaccuracies in overarm
      throws.
AB  - 1. Accurate overarm throwing requires precise control of joint rotations so that
      the ball is released at the appropriate time on the appropriate hand trajectory.
      Inaccuracy in throws, in turn, must result from errors in the control of joint
      rotations. But do high and low throws result from disorders in the joint
      rotations that produce the hand trajectory or in those that cause ball release?
      Are they due to error at a particular joint or to accumulation of errors across a
      number of joints? The objective was to answer these questions and thereby to gain
      insight into the CNS control of joint rotations in a skilled arm movement task.
      2. Ten subjects--male, right-handed recreational ball players, all accurate
      throwers--sat with a fixed trunk and threw tennis balls at a 9 x 9 grid of 6-cm
      target squares 1.5 or 3 m away. Rotations of five arm segments in three
      dimensions were measured at 1,000 Hz with the magnetic-field search-coil
      technique. Hand trajectory (translation) was computed from these rotations. 3.
      The cause of ball high-low inaccuracy was investigated by determining its
      relation with hand kinematic parameters that could potentially affect it. No
      statistically significant relation was found between height of ball impact on the
      target and height of the hand trajectory. In contrast, statistically significant
      relations appeared between height of ball impact on the target and both hand
      trajectory length at ball release (for 8 of 10 subjects) and finger and hand
      orientation in space at ball release (for all 10 subjects). 4. Three hypotheses
      were proposed to explain the variable finger and hand orientations in space at
      ball release, i.e., that they resulted from errors in velocity of rotation at one
      or more proximal joints (wrist, elbow, shoulder), timing of onset of rotation at
      one or more proximal joints, or timing of ball release (due to incorrect velocity
      or timing of onset of finger opening). All three mechanisms could result in
      inappropriate finger and hand orientations in space at ball release, but the
      pattern of joint space trajectories would be different in each case. 5. High and
      low throws did not follow the joint space paths predicted by the first two
      hypotheses. Instead, as predicted by the third hypothesis, a separation of traces
      occurred when finger extension was plotted against wrist flexion or against elbow
      extension, e.g., for a given amplitude of wrist flexion, finger extension was
      large for the high throws and small for the low throws. 6. In agreement, when all
      throws were considered, a statistically significant (P < 0.005) relation was
      found between ball impact height on the target and the amplitude of finger
      extension, for a fixed amplitude of wrist flexion (10 subjects), and for a fixed
      amplitude of elbow extension (8 subjects). Only two subjects showed a
      statistically significant relation between ball impact height and the amplitude
      of wrist flexion, for a fixed amplitude of elbow extension. 7. The separation of
      finger extension-wrist flexion traces in joint space for high and low throws was
      due to a difference in the timing of onset of finger rotation with respect to the
      wrist rather than to an inappropriate velocity of the finger (or the wrist). 8.
      As expected, all 10 subjects showed statistically significant relations between
      the time of onset of finger extension and both finger orientation in space at
      ball release and height of ball impact on the target. 9. It is concluded that in
      fast arm-only throws made by male recreational ball players, high and low throws
      do not primarily result from variability in the height of the hand trajectory or
      from variability in the amplitude of one or more proximal joints due to errors in
      the velocity or timing of onset of these joint rotations. Instead, in most cases,
      they result from inappropriate timing of onset of rotation of the fingers with
      respect to the rotations of the other joints and thus to inappropriate timing of
      ball release. These findings emphasize the im

PMID- 8867115
TI  - Thalamic stimulation-evoked sensations in chronic pain patients and in nonpain
      (movement disorder) patients.
AB  - 1. Little is known about the effect of central and peripheral nervous system
      injury on the processing of somatosensory information at the thalamic level in
      humans. The role of the human thalamic ventrocaudal nucleus (Vc) in nociception
      is not well understood because reports of nociceptive neuronal responses and
      stimulation-evoked pain are rare. In this study, we have characterized effects of
      microstimulation in the tactile region of Vc. Specifically, we investigated the
      incidence of painful sensations evoked by thalamic microstimulation in patients
      with and without chronic pain. 2. Data were obtained during stereotactic thalamic
      procedures for relief of pain or motor disorders. Patients were divided into
      three groups, those with 1) central poststroke pain (PSP, n = 13); 2) nonstroke
      pain (NSP, n = 23); and 3) movement disorders (controls, n = 24). Most (15 of 23)
      of the NSP patients had peripheral nerve damage. Tungsten microelectrodes were
      used to record neuronal responses in the thalamus and to deliver stimuli.
      Localization of tactile Vc was determined according to stereotactic coordinates
      and neuronal responses to innocuous somatic stimuli. At selected sites,
      microstimulation (1-s trains, 300 Hz, 0.1-0.2 ms pulses, < 100 microA) was
      performed and the patient was requested to describe the quality of the sensation
      and its peripheral location (projected field, PF). 3. Microstimulation in tactile
      Vc commonly evoked paresthesia-type sensations. Threshold stimulation never
      evoked pain in the NSP patients and evoked pain at only 2% of Vc sites in the
      movement disorder patients. In these latter 2 groups of patients, stimulation at
      > 98% of Vc sites evoked paresthesia. By contrast, in the PSP patients, 28% of Vc
      sites stimulated evoked painful sensations at threshold. Suprathreshold stimuli
      evoked painful sensations at 46% of Vc sites in the PSP patients but at only 8%
      of Vc sites in NSP patients and 12% of Vc sites in the movement disorder
      patients. 4. The thresholds to evoke paresthesia in the NSP and movement disorder
      patients were significantly lower than the thresholds in the PSP patients.
      However, stimulation thresholds to elicit pain were similar in all patient
      groups. 5. All patients were capable of differentiating stimulation-evoked
      paresthesia from pain. Stimulation-evoked painful sensations in the PSP patients
      were often described as burning and sometimes as "sharp," "shocking," or
      "unpleasant." By contrast, the quality of pain evoked in the other patient groups
      was typically described as unpleasant or shocking. Pain could be evoked at sites
      throughout tactile Vc, although most sites were located in the ventral 2/3 of the
      nucleus. 6. In the movement disorder patients, the location of the projected
      sensation usually corresponded to the location of the receptive fields of the
      tactile neurons recorded at the same site. By contrast, in both groups of pain
      patients there was a high incidence of mismatches between the projected and
      receptive fields. 7. These results suggest that the effective thalamic output
      from Vc to the cortex is affected by somatosensory deafferentation in pain
      patients. In addition, in the PSP patients there are also changes in the
      thalamocortical processing of noxious information. The increased incidence of
      thalamic-evoked pain in PSP patients may be due to 1) loss of low-threshold
      mechanoreceptive thalamic neurons such that nociceptive neuronal output is now
      prominent, 2) reduced tonic inhibition of thalamic or cortical nociceptive
      neurons, and/or 3) unmasking or strengthening of nociceptive pathways.

PMID- 8867116
TI  - Spatial properties of envelope-responsive cells in area 17 and 18 neurons of the
      cat.
AB  - 1. Many neurons in areas 17 and 18 respond to spatial contrast envelope stimuli
      whose Fourier components fall outside the cell's spatial-frequency-selective
      range. The spatial properties of such envelope responses are investigated here
      and compared with responses to conventional luminance-defined gratings to explore
      the underlying receptive-field mechanism. 2. Three spatial properties of envelope
      responses are reported more extensively in this paper. First, the envelope
      responses were selective to the carrier spatial frequency in a narrow range of
      frequencies higher than a given cell's luminance spatial frequency selective
      range (luminance passband). Second, a given cell's dependence on envelope spatial
      frequency often differed from its luminance passband. Last, the optimal carrier
      spatial frequency did not shift systematically with the envelope spatial
      frequency, supporting the hypothesis that the carrier and envelope spatial
      frequency dependencies were mediated by distinct mechanisms. 3. In contrast to
      the direction selectivity to the envelope motion in many envelope-responsive
      cells, no direction preference to carrier motion was found for envelope
      responses. The direction of carrier motion did not alter the direction
      selectivity for envelope motion, further supporting the hypothesis that the
      carrier and envelope temporal properties were mediated by separate mechanisms. 4.
      The distributions of the optimal carrier and luminance spatial frequencies among
      envelope-responsive cells were analyzed. The optimal carrier spatial frequencies
      were randomly distributed from five times the cell's optimal luminance spatial
      frequency to the upper resolution limit of the X-retinal ganglion cells at the
      same retinal eccentricity, suggesting that the selective ranges of envelope
      responses and luminance responses are not strongly correlated over the population
      of envelope-responsive cells. 5. Our data support a "two-stream" receptive-field
      model for envelope-responsive cells. One stream is a conventional, spatially
      linear receptive-field mechanism, mediating luminance responses for the cell; the
      other mediates envelope responses and consists of a two-stage processing: a set
      of spatially small and distributed nonlinear neural subunits whose outputs are
      spatially pooled at the second stage. 6. In conclusion, this study indicates that
      envelope responses in area 17 and 18 neurons cannot be due to a nonlinearity that
      is common to all visual stimuli before narrowband spatial-frequency-selective
      filtering; instead, a specialized processing stream, parallel to the conventional
      luminance response stream, is needed to supplement the traditional luminance
      processing stream in these cells. This specialized stream responds to the
      envelope stimuli and is selective to their carrier and envelope spatial
      frequencies. The distributions of the optimal luminance and carrier spatial
      frequencies indicate a rich variety of possible integration between luminance and
      envelope information.

PMID- 8867117
TI  - Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic
      potentials results from a classical conditioning procedure in the rabbit
      cerebellar slice.
AB  - 1. Using a rabbit cerebellar slice preparation, we stimulated a classical
      conditioning procedure by stimulating parallel fiber inputs to Purkinje cells
      with the use of a brief, high-frequency train of eight constant-current pulses 80
      ms before climbing fiber inputs to the same Purkinje cell were stimulated with
      the use of a brief, lower frequency train of three constant-current pulses. In
      all experiments, we assessed the effects of stimulation by measuring the peak
      amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single
      parallel fiber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs
      underwent a long-term (> 20 min) reduction in peak amplitude (30%) after paired
      stimulation of the parallel and climbing fibers but not after unpaired or
      parallel fiber alone stimulation. We call this phenomenon pairing-specific long
      term depression (PSD). 3. Facilitation of the peak amplitude of a second EPSP
      elicited by a parallel fiber train occurred both before and after paired
      stimulation suggesting that the locus of depression was not presynaptic.
      Depression of the peak amplitude of a depolarizing response to focal application
      of glutamate following pairings of parallel and climbing fiber stimulation added
      support to a suggested postsynaptic locus of the PSD effect. 4. The application
      of aniracetam potentiated EPSP peak amplitude by 40%, but these values returned
      to baseline as a result of pairings. With the removal of aniracetam from the bath
      20 min after pairings, normal levels of pairing-specific EPSP depression were
      observed, indicating that the effect did not result from direct desensitization
      of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors.
      5. Incubation of slices in the protein kinase inhibitor H-7 potentiated EPSP peak
      amplitudes slightly (9%), but peak amplitudes returned to baseline levels after
      pairings. The net reduction in EPSP peak amplitude of < 10% after pairings
      suggested that H-7 partially blocked PSD and that, in turn, PSD involved protein
      kinases. 6. The means of induction and the specificity of those means suggest
      that the phenomenology of PSD is fundamentally different from that of long-term
      depression. PSD only occurs with pairings of trains of parallel fiber and
      climbing fiber stimulation; it occurs without the need for bicuculline; and it
      can overcome the blocking effects of aniracetam. 7. Nevertheless, the involvement
      of protein kinases and the potential role of calcium suggest that the mechanisms
      involved in the induction of PSD and long-term depression have a number of
      features in common. 8. Because of the pairing-specific nature of the long-term
      synaptic depression observed in these experiments, PSD provides a mechanism that
      may contribute to the role of the cerebellar cortex in classical conditioning.

PMID- 8867118
TI  - Neural signals in the monkey ventral striatum related to motivation for juice and
      cocaine rewards.
AB  - 1. The results of neuropsychological, neuropharmacological, and
      neurophysiological experiments have implicated the ventral striatum in reward
      related processes. We designed a task to allow us to separate the effects of
      sensory, motor, and internal signals so that we could study the correlation
      between the activity of neurons in the ventral striatum and different
      motivational states. In this task, a visual stimulus was used to cue the monkeys
      as to their progress toward earning a reward. The monkeys performed more quickly
      and with fewer mistakes in the rewarded trials. After analyzing the behavioral
      results from three monkeys, we recorded from 143 neurons from two of the monkeys
      while they performed the task with either juice or cocaine reward. 2. In this
      task the monkey was required to release its grip on a bar when a small visual
      response cue changed colors from red (the wait signal) to green (the go signal).
      The duration of the wait signal was varied randomly. The cue became blue whenever
      the monkey successfully responded to the go signal within 1 s of its appearance.
      A reward was delivered after the monkey successfully completed one, two, or three
      trials. The schedules were randomly interleaved. A second visual stimulus that
      progressively brightened or dimmed signaled to the monkeys their progress toward
      earning a reward. This discriminative cue allowed the monkeys to judge the
      proportion of work remaining in the current ratio schedule of reinforcement. Data
      were collected from three monkeys while they performed this task. 3. The average
      reaction times became faster and error rates declined as the monkeys progressed
      toward completing the current schedule of reinforcement and thereby earning a
      reward, whereas the modal reaction time did not change. As the duration of the
      wait period before the go signal increased, the monkeys reacted more quickly but
      their error rates scarcely changed. From these results we infer that the effects
      of motivation and motor readiness in this task are generated by separate
      mechanisms rather than by a single mechanism subserving generalized arousal. 4.
      The activity of 138 ventral striatal neurons was sampled in two monkeys while
      they performed the task to earn juice reward. We saw tonic changes in activity
      throughout the trials, and we saw phasic activity following the reward. The
      activity of these neurons was markedly different during juice-rewarded trials
      than during correctly performed trials when no reward was forthcoming (or
      expected). The responses also were weakly, but significantly, related to the
      proximity of the reward in the schedules requiring more than one trial. 5. The
      monkeys worked to obtain intravenous cocaine while we recorded 62 neurons. For 57
      of the neurons, we recorded activity while the monkeys worked in blocks of trials
      during which they self-administered cocaine after blocks during which they worked
      for juice. Although fewer neurons responded to cocaine than to juice reward (19
      vs. 33%), this difference was not significant. The neuronal response properties
      to cocaine and juice rewards were independent; that is, the responses when one
      was the reward one failed to predict the response when the other was the reward.
      In addition, the neuronal activity lost most of its selectivity for rewarded
      trials, i.e, the activity did not distinguish nearly as well between cocaine and
      sham rewards as between juice and sham rewards. 6. Our results show that
      mechanisms by which cocaine acts do not appear to be the same as the ones
      activated when the monkeys were presented with an oral juice reward. This finding
      raises the intriguing possibility that the effects of cocaine could be reduced
      selectively without blocking the effects of many natural rewards.

PMID- 8867119
TI  - Dynamic behavior of a neural network model of locomotor control in the lamprey.
AB  - 1. Experimental studies have shown that a central pattern generator in the spinal
      cord of the lamprey can produce the basic rhythm for locomotion. This pattern
      generator interacts with the reticular neurons forming a spinoreticulospinal
      loop. To better understand and investigate the mechanisms for locomotor pattern
      generation in the lamprey, we examine the dynamic behavior of a simplified neural
      network model representing a unit spinal pattern generator (uPG) and its
      interaction with the reticular system. We use the techniques of bifurcation
      analysis and specifically examine the effects on the dynamic behavior of the
      system of 1) changing tonic drives to the different neurons of the uPG; 2)
      altering inhibitory and excitatory interconnection strengths among the uPG
      neurons; and 3) feedforward-feedback interactions between the uPG and the
      reticular neurons. 2. The model analyzed is a qualitative left-right symmetric
      network based on proposed functional architecture with one class of phasic
      reticular neurons and three classes of uPG neurons: excitatory (E), lateral (L),
      and crossed (C) interneurons. In the model each class is represented by one left
      and one right neuron. Each neuron has basic passive properties akin to
      biophysical neurons and receives tonic synaptic drive and weighted synaptic input
      from other connecting neurons. The neuron's output as a function of voltage is
      given by a nonlinear function with a strict threshold and saturation. 3. With an
      appropriate set of parameter values, the voltage of each neuron can oscillate
      periodically with phase relationships among the different neurons that are
      qualitatively similar to those observed experimentally. The uPG alone can also
      oscillate, as observed experimentally in isolated lamprey spinal cords. Varying
      the parameters can, however, profoundly change the state of the system via
      different kinds of bifurcations. Change in a single parameter can move the system
      from nonoscillatory to oscillatory states via different kinds of bifurcations.
      For some parameter values the system can also exhibit multistable behavior (e.g.,
      an oscillatory state and a nonoscillatory state). The analysis also shows us how
      the amplitudes of the oscillations vary and the periods of limit cycles change as
      different bifurcation points are approached. 4. Altering tonic drive to just one
      class of uPG neurons (without altering the interconnections) can change the state
      of the system by altering the stability of fixed points, converting fixed points
      to oscillations, single oscillations to two stable oscillations, etc. Two
      parameter bifurcation diagrams show the critical regions in which a balance
      between the tonic drives is necessary to maintain stable oscillations. A minimum
      tonic drive is necessary to obtain stable oscillatory output. With appropriate
      changes in the tonic drives to the L and C neurons, stable oscillatory output can
      be obtained even after eliminating the E neurons. Indeed, the presence of active
      E neurons in the biological system does not prove they play a functional role in
      the system, because tonic drive from other sources can substitute for them. On
      the other hand, very high excitation of any one class of neurons can terminate
      oscillations. Appropriate balance of tonic drives to different neuron classes can
      help sustain stable oscillations for larger tonic drives. Published experimental
      results concerning changes in amplitude and swimming frequency with increased
      tonic drives are mimicked by the model's responses to increased tonic drive. 5.
      Interconnectivity among the neurons plays a crucial role. The analysis indicates
      that the C and L classes of neurons are essential components of the model
      network. Sufficient inhibition from the L to C neurons as well as mutual
      inhibition between the left and right halves is necessary to obtain stable
      oscillatory output. When the E neurons are present in the model network, they
      must receive appropriate tonic drive and provide appropriate excitation

PMID- 8867120
TI  - Changes in the control of arm position, movement, and thalamic discharge during
      local inactivation in the globus pallidus of the monkey.
AB  - 1. To examine the effect of disruption of basal ganglia output on limb stability
      and movement, muscimol was injected into the internal globus pallidus (GPi) of
      monkeys trained to make arm movements to visible or remembered targets in a two
      dimensional workspace. 2. Injections of as little as 0.25 micrograms muscimol at
      GPi sites at which pallidal neurons with arm movement activity had been recorded
      were followed by drift of the contralateral arm within < 10 min. Drift was
      usually in the flexor direction. Injections at a few sites in or near the
      external pallidal segment sometimes were followed by extensor drift. 3. Drift was
      active (accompanied by activation of agonist muscles), but could be overcome by
      the animal, resulting in an oscillating movement off and on the required
      position. 4. The pallidal-receiving (PR) area of the thalamus was identified by
      recording the response of thalamic neurons to stimulation in the globus pallidus.
      The activity of 15 neurons identified as PR cells (n = 6) or within the PR region
      was recorded both before and after injection of muscimol into GPi. After the
      injection, the tonic discharge increased during the hold period in 47% of the
      cells studied. When postural drift also occurred, there was a close temporal
      correlation between the postinjection time at which drift occurred and the time
      at which the tonic discharge rate increased in thalamic neurons that were clearly
      related to arm movement. 5. The peak velocity of arm movements to visible or
      remembered visual target locations was decreased after injection of muscimol into
      GPi, sometimes with an increase in movement time. 6. The firing rate of PR
      thalamic neurons after injection of muscimol was also increased during the
      perimovement period. Because of the increase in the tonic discharge rate,
      however, the phasic movement-related change in activity could stay the same or
      even decrease. Postinjection changes in this movement-related phasic activity,
      however, were not necessarily coincident with changes in peak movement velocity.
      7. Changes in reaction time were variable after injection of muscimol. In some
      cases it was increased, and in others decreased. The time of onset of phasic
      movement-related changes in the activity of PR neurons studied was not altered by
      the injection. 8. Our data indicate that the tonic inhibitory output of GPi, in
      particular to the cortical motor areas, is especially important in the
      maintenance of postural stability. In the absence of normal pallidal output,
      desired limb position can be achieved on the basis of either current or prior
      visual cues, but targeted movements are slowed.

PMID- 8867121
TI  - Contrasting locations of pallidal-receiving neurons and microexcitable zones in
      primate thalamus.
AB  - 1. In two awake, juvenile male Macaca fascicularis monkeys, microstimulation was
      applied in ventralis anterior (VA), ventralis lateralis (VL), or ventralis
      posterior lateralis (VPL) of the thalamus. Thalamic recording was used to
      identify the region that contained pallidal-receiving (PR) thalamic neurons,
      cells that responded orthodromically to stimulation in the internal pallidal
      segment (GPi). Thalamic stimulation was used to elicit motor responses.
      Penetrations in the thalamus and the pallidum focused on areas with activity
      related to contralateral arm movement. Fifty-one PR cells were identified
      electrophysiologically in VL oralis (VLo), VL caudalis (VLc) and VA pars
      parvocellularis (VApc). 2. With a subject at rest, trains of stimuli were applied
      through the thalamic microelectrode. Palpable or visible muscle twitches or joint
      movements were evoked by short trains (12 pulses) of stimuli applied in VLc and
      VPL oralis (VPLo); thresholds there ranged from 5 to 75 microA. In VA and VLo,
      areas where PR neurons were located, even longer trains (24 pulses) of stimuli
      with currents up to 200 microA usually failed to evoke movement. In the caudal
      portions of VLo, near VPLo, there were some microexcitable sites found near PR
      cells where stimuli at approximately 50 microA elicited movement. 3. From
      microstimulation studies combined with histological reconstruction, Ashe and co
      workers hypothesized that microexcitable zones were cerebellar receiving areas
      (CR) and nonexcitable zones were PR areas. Our data support theirs and add
      electrophysiological identification of PR areas. Further, we injected wheat germ
      agglutinin-horseradish peroxidase (WGA-HRP) into the thalamus at one of the more
      rostral microexcitable sites, just caudal and lateral to identified PR cells. The
      tetra-methyl benzidine-reacted HRP label was found in the contralateral deep
      cerebellar nuclei (DCN) but not in ipsilateral GPi, showing that even this
      rostral microexcitable zone was a CR area. 4. Together with evidence from the
      literature, the data are consistent with the hypothesis that PR cells have
      relatively weak access to spinal-destined motor outputs, whereas thalamocortical
      neurons from VPLo and VLc have more secure access. In addition to characteristics
      of cell discharge and responses to somatosensory stimulation, microexcitability
      may be a further aid in tentative electro-physiological identification of PR
      versus CR areas of the motor thalamus without necessarily recording thalamic
      neuronal responses to stimulation in GPi or the DCN.

PMID- 8867122
TI  - Capsaicin-induced rapid receptive field reorganization in cuneate neurons.
AB  - 1. To determine whether activity in unmyelinated or thinly myelinated primary
      afferents affects the organization of cutaneous receptive fields (RFs) in the
      cuneate nucleus, subcutaneous injections of capsaicin were made into the RFs of
      cuneate neurons in anesthetized cats. The effects of capsaicin injection on RF
      size and position, response properties, and spontaneous firing rates were
      determined during single-unit recordings. 2. Subcutaneous injection of capsaicin
      (10% dissolved in 70% ethanol) into peripheral RFs produced rapid RF
      reorganization in all neurons tested (n = 20), even when the original RF remained
      responsive to tactile stimulation. RF reorganization was marked by the appearance
      of newly responsive RFs. These RFs appeared as either contiguous expansions of
      the original RF or as new, noncontiguous fields. Control injections of the
      vehicle alone never produced RF reorganization (n = 9). RF reorganization was not
      related to changes in spontaneous activity. 3. Following capsaicin-induced RF
      reorganization, subcutaneous injections of lidocaine were made into the original
      RFs (n = 8). These injections produced no additional RF reorganization in seven
      of the eight neurons, even though in each case the lidocaine injections produced
      at least partial blocks of responsiveness from within the original RF. 4. In
      approximately one-half of the neurons (9 of 20), the reorganized RFs had response
      properties that were different from those of the original RF. This result
      suggests that, for neurons in the dorsal column nuclei (DCN), physiological
      mechanisms that normally mask inputs and restrict RF size can give rise to
      response specificity. 5. The results of these experiments demonstrate that
      capsaicin-induced RF reorganization, which has been reported previously in
      ventrobasal thalamus and primary somatosensory cortex, can arise within the
      dorsal column-medial lemniscal system, at the level of the DCN. The present
      results also provide evidence that rapid RF reorganization in cuneate neurons can
      be produced by blockade of a subset of peripheral afferents that are sensitive to
      capsaicin.

PMID- 8867123
TI  - Contribution of hind limb flexor muscle afferents to the timing of phase
      transitions in the cat step cycle.
AB  - 1. In this investigation, we tested the hypothesis that muscle spindle afferents
      signaling the length of hind-leg flexor muscles are involved in terminating
      extensor activity and initiating flexion during walking. The hip flexor muscle
      iliopsoas (IP) and the ankle flexors tibialis anterior (TA) and extensor
      digitorum longus (EDL) were stretched or vibrated at various phases of the step
      cycle in spontaneously walking decerebrate cats. Changes in electromyogram
      amplitude, duration, and timing were then examined. The effects of electrically
      stimulating group I and II afferents in the nerves to TA and EDL also were
      examined. 2. Stretch of the individual flexor muscles (IP, TA, or EDL) during the
      stance phase reduced the duration of extensor activity and promoted the onset of
      flexor burst activity. The contralateral step cycle also was affected by the
      stretch, the duration of flexor activity being shortened and extensor activity
      occurring earlier. Therefore, stretch of the flexor muscles during the stance
      phase reset the locomotor rhythm to flexion ipsilaterally and extension
      contralaterally. 3. Results of electrically stimulating the afferents from the TA
      and EDL muscles suggested that different groups of afferents were responsible for
      the resetting of the step cycle. Stimulation of the TA nerve reset the locomotor
      step cycle when the stimulus intensity was in the group II range (2-5 xT). By
      contrast, stimulation of the EDL nerve generated strong resetting of the step
      cycle in the range of 1.2-1.4 xT, where primarily the group Ia afferents from the
      muscle spindles would be activated. 4. Vibration of IP or EDL during stance
      reduced the duration of the extensor activity by similar amounts to that produced
      by muscle stretch or by electrical stimulation of EDL at group Ia strengths. This
      suggests that the group Ia afferents from IP and EDL are capable of resetting the
      locomotor pattern generator. Vibration of TA did not affect the locomotor rhythm.
      5. Stretch of IP or electrical stimulation of TA afferents (5 xT) during the
      flexion phase did not change the duration of the flexor activity. Stimulation of
      the EDL nerve at 1.8-5 xT during flexion increased the duration of the flexor
      activity. In none of our preparations did we observe resetting to extension when
      the flexor afferents were activated during flexion. 6. We conclude that as the
      flexor muscles lengthen during the stance phase of gait, their spindle afferents
      (group Ia afferents for EDL and IP, group II afferents for TA) act to inhibit the
      spinal center generating extensor activity thus facilitating the initiation of
      swing.

PMID- 8867124
TI  - Whole cell calcium currents in acutely isolated olfactory bulb output neurons of
      the rat.
AB  - 1. Voltage-gated whole cell Ca2+ currents have been investigated in olfactory
      bulb (OB) output neurons acutely isolated from neonatal rats. 2. Identification
      of OB output neurons, mitral or tufted cells, was based on morphology and size
      and validated by their retrograde labeling with rhodamine or Fast Blue. Of
      labeled neurons, 45% exhibited either phasic or nonphasic spontaneous firing that
      was blocked by 10(-7) M tetrodotoxin, 0.5 mM Cd2+, or 1 mM Co2+ in the bathing
      solution. 3. Whole cell Ca2+ currents displayed holding potential sensitivity
      indicative of low voltage-activated (LVA) and high voltage-activated (HVA)
      currents, which exhibited similar dependence on extracellular Ca2+ concentration
      and could be completely abolished by bathing in 500 microM Cd2+ or in Ca(2+)-free
      solution. 4. A T-type LVA Ca2+ current, detected in 65% of OB output neurons
      tested, was activated by depolarizing to -57 mV from holding potential -86 mV and
      fully inactivated at holding potentials more positive than -60 mV. It was
      permeated equally by 2.6 mM Ca2+, Sr2+ and Ba2+. The half-activation potential
      was -35 mV with a slope factor of 7 mV. Depolarizing to -26 mV from different
      holding potentials in a 2.6-mM Ca2+ solution gave a steady-state half
      inactivation potential of -82 mV with a slope factor of 10.7 mV. This LVA current
      was not sensitive to 5 microM omega-conotoxin (omega-CgTx) or 5 microM Bay K 8644
      and was resistant to block by 30 microM Cd2+, by 50 microM verapamil or by 5
      microM nifedipine. 5. HVA Ca2+ currents, detected in 97% of OB output cells,
      activated at around -30 to -20 mV, with maximum peak current at approximately 4
      mV in 2.6 mM Ca2+ external solution. They showed similar permeability to 2.6 mM
      Ca2+ and Sr2+, but the maximum peak current was increased 40% in 2.6 mM Ba2+.
      Depolarizing to 4 mV from different holding potentials yielded a half
      inactivation potential of -67 mV with a slope factor of 13.2 mV. Two components,
      as suggested by their sensitivities to 5 microM Bay K 8644, nifedipine. omega
      CgTx and to voltage, may resemble the L-type and N-type currents described in
      other neural preparations. However, 5 microM omega-CgTx seemed to block both
      components, being more effective at more positive potentials. There was a
      residual component of Cd(2+)-sensitive current not affected by cumulative
      addition of nifedipine and omega-CgTx. 6. omega-Agatoxin IVA (omega-Aga), a
      selective P-type Ca2+ channel blocker, had no detectable effect at 50 or 200 nM
      and 1 microM doses on whole cell Ca2+ currents elicited by 200-ms voltage steps
      to 4 mV from holding potential -86 mV. 7. We conclude that both LVA and HVA Ca2+
      currents exist in neonatal rat OB output neurons, showing distinct kinetic and
      pharmacological characteristics. The HVA Ca2+ currents contain at least two
      components, probably resembling L- and N-type currents. Another fast-inactivating
      HVA component, insensitive to nifedipine, omega-CgTx and omega-Aga, could
      represent the newly established R-type Ca2+ current.

PMID- 8867125
TI  - Active-sleep-related suppression of feline trigeminal sensory neurons: evidence
      implicating presynaptic inhibition via a process of primary afferent
      depolarization.
AB  - 1. Changes in the excitability of lumbar and trigeminal primary afferent
      terminals have long been used as an index of primary afferent depolarization
      (PAD). PAD has been linked in part to the presynaptic inhibition of
      neurotransmission. During the behavioral state of active sleep, synaptic
      transmission through the rostral trigeminal sensory nuclear complex (TSNC) is
      suppressed when compared with other states such as wakefulness or quiet sleep.
      The mechanism underlying the suppression of neuronal activity in the rostral TSNC
      during active sleep is not known. Accordingly, experiments were conducted to
      determine, by examining the excitability of tooth pulp afferent terminals in cat
      during sleep and wakefulness, whether PAD processes might contribute in part to
      the suppression of rostral TSNC neuron activity. 2. Unitary potentials recorded
      in the maxillary canine tooth pulp were evoked by low-intensity stimuli applied
      to the rostral TSNC. Unitary potentials were identified by their "all-or-nothing"
      response, their invariant amplitude and latency, and their ability to follow a
      short train of high-frequency (333 Hz) stimuli. 3. The firing index (FI), a
      measure of the probability of evoking a unitary potential, was used to assess the
      changes in excitability of tooth pulp primary afferents. The proximity of
      stimulating electrodes to the terminal segment rather than a nonterminal segment
      of a tooth pulp afferent was demonstrated by observing an increase in the FI as a
      consequence of conditioning stimuli applied to ipsilateral branches of the
      trigeminal nerves. Increases in the FI over baseline were obtained for
      conditioning test intervals ranging from 20 to 80 ms, with the peak effect of
      conditioning occurring at 30 ms. 4. A total of 25 tooth pulp afferent terminals
      were identified and changes in their FI were examined during wakefulness, quiet
      sleep, and active sleep. The FI for all 25 terminals during wakefulness (FIW:
      0.29 +/- 0.04, mean +/- SE) did not differ from that during quiet sleep (0.32 +/-
      0.04). However, when compared with wakefulness, the FI during active sleep (FIAS:
      0.52 +/- 0.07) was increased. The mean ratio of change in the FI (FIAS/FIW) was
      3.5 +/- 0.9. These findings indicate that, as a population, tooth pulp afferent
      terminals are depolarized during the state of active sleep and that PAD processes
      may partly underlie the suppression of synaptic transmission through the rostral
      TSNC during this state. 5. To explore whether presynaptic excitability changes
      underlie the modulation of rostral TSNC neuron activity during active sleep,
      additional experiments were performed in which tooth-pulp-evoked responses of
      individual rostral TSNC neurons and the FIs of adjacent individual tooth pulp
      afferent terminals were analyzed as a function of sleep and wakefulness. The
      results indicated that active-sleep-related PAD was associated with active-sleep
      related suppression of tooth-pulp-evoked activity of rostral TSNC neurons. 6. The
      conclusion is reached that PAD processes contribute to the mechanism whereby
      synaptic activity through the rostral TSNC is suppressed during the behavioral
      state of active sleep.

PMID- 8867126
TI  - Role of suppression in shaping orientation and direction selectivity of complex
      neurons in cat striate cortex.
AB  - 1. Single binocularly driven complex neurons in cat striate cortex were recorded
      extracellularly under nitrous oxide-oxygen-halothane anesthesia and muscle
      relaxant. Orientational/directional tuning was initially derived for each eye in
      turn, with sine wave gratings of optimal spatial frequency and velocity, while
      the other eye viewed a uniform field. 2. For the dominant eye, previously
      concealed suppression was revealed against elevated levels of firing induced with
      a conditioning grating, drifting continuously in the preferred direction,
      simultaneously presented to the nondominant eye. During steady-state binocular
      conditioning, orientational/directional tuning was reestablished for the dominant
      eye. In a subset of cells, tuning curves during conditioning were also derived
      for the reverse configuration, i.e., nondominant eye tuning, dominant eye
      conditioning: results were qualitatively identical to those for conditioning
      through the nondominant eye. 3. Neurons were initially segregated into five
      groups, according to the observed suppression profiles induced at nonoptimal
      orientations/directions during conditioning: Type 1, suppression centered on
      orthogonal directions; Type 2, suppression around null directions; Type 3, null
      suppression combined with orthogonal suppression; Type 4, lateral suppression,
      maximal for directions immediately flanking those inducing excitation; and Type
      5, the residue of cells, totally lacking suppression or showing complex or
      variable suppression. 4. Sharpness of (excitatory) tuning was correlated with
      directionality and with class of suppression revealed during binocular
      conditioning. Direction-biased neurons were more sharply orientation tuned than
      direction-selective neurons; similarly, neurons exhibiting lateral or orthogonal
      suppression during conditioning were more sharply tuned than neurons with null
      suppression. 5. Application of suboptimal directions of conditioning weakened the
      induced suppression but altered none of its main characteristics. 6. The
      relationship between excitation, suppression, and spatial frequency was
      investigated by comparing tuning curves for the dominant eye at several spatial
      frequencies, without and during conditioning. End-stopped neurons preferred lower
      spatial frequencies and higher velocities of motion than non-end-stopped neurons.
      Confirming previous reports, suppression in some neurons was still present for
      spatial frequencies above the cutoff frequency for excitation, demonstrating the
      tendency for suppression to be more broadly spatial frequency tuned than
      excitation. 7. Scatterplots of strength of suppression, in directions orthogonal
      and opposite maximal excitation, partially segregated neurons of Types 1-3.
      Clearer segregation of Types 1-4 was obtained by curve-fitting to profiles of
      suppression, and correlating half-width of tuning for suppression with the angle
      between the directions of optimal suppression and optimal excitation in each
      neuron. 8. Two interpretations are advanced-the first, based on three discrete
      classes of inhibition, orthogonal, null and lateral; the second, based on only
      two classes, orthogonal and null/lateral--in which null and lateral suppression
      are manifestations of the same inhibitory mechanism operating, respectively, on
      broadly tuned direction-selective or on sharply tuned direction-biased neurons.
      Orthogonal suppression may be untuned for direction, whereas lateral and null
      suppression are broadly direction tuned. Within each class, suppression is more
      broadly spatial frequency tuned than excitation. 9. It is concluded that
      orientational/directional selectivity of complex cells at different spatial
      frequencies is determined by the balance between tuned excitation and varying
      combinations of relatively broadly distributed or untuned inhibition.

PMID- 8867127
TI  - Mechanical response properties of nociceptors innervating feline hairy skin.
AB  - 1. The responses of feline cutaneous nociceptors were examined in vivo by
      systematically manipulating the intensive and spatial dimensions of mechanical
      stimulation. A computer-controlled motor was used to apply prescribed forces (5
      90 g) to a nociceptor's receptive field, with flat-tipped, cylindrical probes of
      various sizes (contact areas: 0.1-5.0 mm2). The stimulating device and protocols
      were similar to those previously used to evaluate human perception, thus allowing
      for comparisons of the two data sets. 2. With a ramp-and-hold stimulus of
      controlled force, most nociceptors showed a slowly adapting (SA) response
      throughout the stimulus. In this way, nociceptors resembled low-threshold SA
      mechanoreceptors. However, in contrast to SA mechanoreceptors, nociceptors failed
      to exhibit an onset burst of activity associated with the stimulus ramp. Nineteen
      percent (6 of 31) of the nociceptors often showed the opposite trend during the
      stimulus, e.g., a gradually increasing firing rate. Most of these nociceptors (5
      of 6) had particularly high mechanical thresholds. 3. With 30 stimuli repeated at
      short intervals (6-8 s), response rates tended to decrease across trials. This
      phenomenon was most evident with more intense stimuli. When two series of stimuli
      were separated by 4-5 min, there was no apparent trend of reduced responsiveness
      between series. 4. Overall, nociceptors responded in an orderly way to variations
      in force and probe size. For a given probe size, larger forces produced greater
      responses; for a given force, smaller probes produced greater responses. The
      relationship between probe size and force was best described as an even tradeoff
      between force and a linear dimension of the probe (i.e., probe perimeter), rather
      than the area of the probe. Thus a given pressure (force/area) did not evoke the
      same response from nociceptors as probe size was varied. 5. There were two
      significant differences in the mechanical responsiveness between A fiber and C
      fiber nociceptors. First, for a given set of stimuli, A fiber nociceptors
      exhibited a greater response rate than the C fiber nociceptors. Second, the A
      fiber nociceptors exhibited a greater differential response related to probe size
      than the C fiber nociceptors. On the basis of these two features, the A fiber
      nociceptors' response profiles showed a closer parallel with previously reported
      human pain thresholds than the C fiber nociceptors did. 6. When the nociceptors
      were subdivided as to their mechanical threshold, those with lower thresholds
      [mechanically sensitive afferents (MSAs)] showed a response saturation with the
      more intense stimuli. On average, the stimulus levels at which saturation
      occurred were close to human pain threshold. Those nociceptors with higher
      thresholds [mechanically insensitive afferents (MIAs)] did not show such
      saturation. Thus only the MIAs appeared to have the capacity to unambiguously
      encode mechanical stimulus intensities above pain threshold. The MSAs, on the
      other hand, exhibited their greatest dynamic response range near the threshold
      for nonpainful sharpness. Thus the group of afferents commonly defined as
      nociceptors exhibit a heterogeneity of mechanical response properties, which may
      serve functionally different roles for perception.

PMID- 8867128
TI  - Effects of rhinal cortex lesions combined with hippocampectomy on visual
      recognition memory in rhesus monkeys.
AB  - 1. We assessed the visual recognition abilities, as measured by delayed
      nonmatching-to-sample with trial-unique objects, of rhesus monkeys with
      hippocampectomy (i.e., removal of the hippocampal formation plus parahippocampal
      gyrus) combined with ablations of the rhinal cortex (i.e., entorhinal cortex plus
      perirhinal cortex). 2. Relative to unoperated controls, monkeys with combined
      hippocampectomy and rhinal cortex ablation (H+Rh) were significantly impaired in
      visual recognition. 3. Comparison of the scores of the monkeys in the present
      H+Rh group, which sustained near-complete rhinal cortex damage, with the scores
      of monkeys in an earlier H+Rh group in which the rostral part of the rhinal
      cortex had been spared indicates that the magnitude of the impairment is greater
      in the group with the more complete rhinal cortex damage. This finding is
      consistent with the idea that the rhinal cortex is critical for visual
      recognition. 4. Comparison of the present results with those from an earlier
      study on visual recognition that employed lesions limited to the rhinal cortex
      (Rh group) shows, paradoxically, that adding removal of the hippocampal formation
      and parahippocampal gyrus to a rhinal cortex lesion significantly reduces the
      recognition impairment produced by rhinal cortex lesions alone. 5. Our findings
      do not fit the view that the hippocampal formation, parahippocampal gyrus, and
      rhinal cortex constitute parts of a single functional system, such that the
      greater the damage to the entire system, the more severe the impairment. Instead,
      the results are consistent with the view that there are multiple functional
      subdivisions within the medial temporal lobe.

PMID- 8867129
TI  - Cortical synthesis of azimuth-sensitive single-unit responses with nonmonotonic
      level tuning: a thalamocortical comparison in the cat.
AB  - 1. Azimuth and sound pressure level (SPL) tuning to noise stimulation was
      characterized in single-unit samples obtained from primary auditory cortex (AI)
      and in areas of the medial geniculate body (MGB) that project to AI. The primary
      aim of the study was to test the hypothesis that AI is an important site of
      synthesis of single-unit responses that exhibit both azimuth sensitivity
      (tendency for directionally restricted responsiveness) and nonmonotonic (NM)
      level tuning (tendency for decreased responsiveness with increasing SPL). This
      was accomplished by comparing the proportions of such responses in AI and MGB. 2.
      Samples consisted of high-best-frequency (BF) single units located in MGB (n =
      217) and AI (n = 216) of barbiturate-anesthetized cats. The MGB sample was
      obtained mainly from recording sites located in two nuclei that project to AI,
      the ventral nucleus (VN, n = 118) and the lateral part of the posterior group of
      thalamic nuclei (Po, n = 84). In addition, a few MGB units were obtained from the
      medial division (n = 8) or uncertain locations (n = 7). Each unit's responses
      were studied using noise bursts presented from azimuthal sound directions
      distributed throughout 180 degrees of the frontal hemifield at 0 degrees
      elevation. SPL was varied over an 80-dB range in steps of < or = 20 dB at each
      location. Similarities and differences in azimuth and level tuning were evaluated
      statistically by comparing the AI sample with the entire MGB sample. If they were
      found to differ, the AI, VN, and Po samples were compared. 3. Azimuth function
      modulation was used as a measure of azimuth sensitivity, and its mean was greater
      in AI than in MGB. NM strength was defined as the percentage reduction in level
      function value at 75 dB SPL and its mean was greater in AI (showing a greater
      tendency for decreased responsiveness) than in MGB. Azimuth-sensitive (AS) NM
      units were identified by jointly categorizing each sample according to both
      azimuth sensitivity (sensitive and insensitive categories) and NM strength (NM
      and monotonic categories). AS NM units were much more common in the AI sample
      than in any of the MGB samples, suggesting that some such responses are
      synthesized in AI. 4. A vast majority of AI NM units have been reported to be AS,
      showing a preferential association (linkage) between these two response
      properties. This finding was confirmed in AI, but was not found to be the case in
      MGB. This suggests that a linkage between these response properties emerges in
      the cortex, presumably as a result of synthesis of NM AS responses. Although the
      functional significance of the linkage is unknown, NM responses may reflect
      excitatory/inhibitory antagonism that provides AS AI neurons with sensitivity to
      stimulus features beyond that which is present in MGB. 5. Breadth of azimuth
      tuning of AS cells was measured as the portion of the frontal hemifield over
      which azimuth function values were > 75% of maximum (preferred azimuth range,
      PAR). PARs were broadly distributed in each structure, and mean PAR was narrower
      in AI than in MGB. A preferred level range (PLR) was defined for NM level
      functions as the range over which values were > 75% of maximum, and mean PLRs
      were similar in each sample. There was a weak, but significant, positive
      correlation between PARs and PLRs in AI but not in MGB. This further suggests a
      linkage between azimuth and level tuning in AI that does not exist in MGB. 6.
      Best azimuth (midpoint of the PAR) was used to classify cells as contralateral
      preferring, ipsilateral preferring, midline preferring, or multipeaked. Samples
      from AI and MGB exhibited similar distributions of these categories.
      Contralateral-preferring cells represented a majority of each sample, whereass
      midline-preferring, ipsilateral-preferring, and multipeaked cells each
      represented smaller proportions. This suggests that the azimuth preference
      distribution in AI largely reflects that in MGB. 7. A best SPL was defined as the
      midpoint of the PLR. This wa

PMID- 8867130
TI  - Presynaptic inhibition of sensory neurons during kicking movements in the locust.
AB  - 1. Locusts use a distinctive motor pattern to extend the tibia of a hind leg
      rapidly in a defensive kick, or to extend the tibiae of both hind legs in a jump.
      The force for the movement is generated by an almost isometric co-contraction of
      the extensor and flexor tibiae muscles followed by a sudden release of the stored
      energy when the flexor motor neurons are inhibited. A proprioceptor (the femoral
      chordotonal organ) spans the femorotibial joint, and at least 50 of its sensory
      neurons each signal particular features of its movements. Intracellular
      recordings from these neurons close to their terminals in the CNS show that their
      spikes during kicking are superimposed on a depolarizing synaptic input generated
      near their output terminals. The depolarization is linked to the time in the
      motor pattern when the sensory neurons spike. 2. Flexion-sensitive neurons spike
      and their terminals are depolarized when the tibia is initially flexed and when
      the tibia rebounds from the rapid extension of the kick. Some respond phasically,
      others more tonically and over different ranges of joint angles, but all receive
      a depolarizing synaptic input when they spike. The depolarization of the
      terminals precedes the spikes and often occurs concurrently with the changes in
      the membrane potentials of the motor neurons. The input persists while the tibia
      is held fully flexed before the kick. 3. Extension-sensitive neurons spike and
      their terminals are depolarized when the tibia is rapidly extended and this
      depolarization may outlast the spikes at the completion of a kick. Some of these
      depolarizing synaptic potentials occur before the movement starts, which suggests
      that they may result from central elements of the motor pattern; others however
      are clearly consequent upon joint movements. During the co-contraction that
      precedes the movement, these neurons do not spike and their membrane potential
      repolarizes because of a reduction in the synaptic input. 4. The depolarizing
      synaptic potentials are associated with a fall in the resistance of the membrane
      and may be attributed to the same gamma-aminobutyric acid-mediated mechanism
      already identified at the terminals of these sensory neurons. The effect and
      timing of the depolarization of the terminals during this voluntary movement
      should be to reduce the effectiveness of the sensory neurons in transmitting
      signals to their postsynaptic neurons in the CNS. This could therefore be part of
      a mechanism that allows voluntary movements to proceed in the presence of self
      generated sensory feedback which might otherwise impede that movement.

PMID- 8867131
TI  - Spatially tuned auditory responses in area LIP of macaques performing delayed
      memory saccades to acoustic targets.
AB  - 1. The lateral intraparietal area (area LIP) of the macaque's posterior parietal
      cortex (PPC) lies in the dorsal stream of extrastriate visual areas. It receives
      extensive visual inputs and sends outputs to several eye movement centers. It
      contains neurons with visual and saccade-related responses suggesting a role of
      area LIP in programming saccadic eye movements to visual targets. Because
      primates can also orient to nonvisual stimuli, we investigated whether LIP
      neurons process stimuli of other modalities besides the visual one by comparing
      their activity in auditory and visual saccade tasks. 2. We recorded the activity
      of single neurons of Macaca mulatta monkeys while they performed memory saccades
      to acoustic and visual targets. We analyzed the activity during stimulus
      presentation (stimulus period, S) and during the delay (memory period, M) between
      stimulus presentation and the saccade to its remembered location. 3. Among 80
      area LIP neurons tested, we found 44 that had S period and/or M period responses
      following presentation of the auditory stimulus. Most of these responses were
      spatially tuned, i.e., selective for the left or right stimulus location (27 of
      29 S responses; 25 of 29 M responses). 4. The majority of neurons with responses
      in the auditory memory saccade task also responded in the visual version of the
      task. Eighty-nine percent (24/27) were clearly bimodal in the S period, and 88%
      (23/26) were bimodal in the M period. 5. Almost all the neurons with spatially
      tuned auditory responses that were bimodal were also spatially tuned in their
      visual responses (20/22 for S responses; 18/19 for M responses). The spatial
      tuning for the two modalities was the same in 85% (17/20) of the tested neurons
      for the S responses, and in 83% (15/18) of the tested neurons for the M
      responses. 6. Area LIP contains a population of neurons that respond to both
      visual and auditory stimuli. This result is consistent with our finding that the
      memory activity of many LIP cells encodes the next planned saccade. If cells are
      coding planned movements, they should be active independently of the sensory
      modality of the target for the movement, as was the case for most of the neurons
      described in the present study.

PMID- 8867132
TI  - Tilt responses of neurons in the caudal descending nucleus of the decerebrate
      cat: influence of the caudal cerebellar vermis and of neck receptors.
AB  - 1. In decerebrate cats with intact cerebellums, we studied the responses of
      neurons in the caudal areas of the vestibular nuclei to natural vestibular
      stimulation in vertical planes and to neck rotation. The activity of most neurons
      was recorded in the caudal half of the descending nucleus. 2. One goal of our
      experiments was to compare the dynamic and spatial properties of responses to
      sinusoidal vestibular stimulation with those seen in previous experiments in
      which the caudal cerebellar vermis, including the nodulus and uvula, was removed.
      This part of the cerebellum receives vestibular input and projects to the caudal
      areas of the vestibular nuclei, suggesting that it could influence responses to
      stimulation of the labyrinth. 3. As in our previous experiments, most neurons
      could be classified as receiving predominant input either from the otoliths or
      from one vertical semicircular canal. When mean gain and phase and response
      vector orientations were compared, there were no obvious differences between the
      behavior of neurons in the partially decerebellate preparation and the one with
      the cerebellum intact, demonstrating that in the decerebrate cat the nodulus and
      uvula have little or no influence on the processing of vertical vestibular input
      in this region of the vestibular nuclei. 4. Only 23 of 74 (31%) of neurons tested
      responded to neck rotation. This contrasts with the much larger fractions that
      respond to this stimulus in Deiters' nucleus and in the rostral descending
      nucleus. We also recorded from neurons near the vestibular nuclei, mainly in the
      external cuneate nucleus. All of them (9 of 9) responded to neck rotation. 5.
      Responses to neck rotation also differed in their dynamics from those found more
      rostrally in the vestibular nuclei. Dynamics of more rostral neurons resemble
      those of neck muscle spindles, as do those of external cuneate neurons. The
      dynamics of caudal vestibular neurons, on the other hand, have a steeper gain
      slope and more advanced phases than do those of neurons in the more rostral
      vestibular nuclei. This suggests the possibility of involvement of additional
      receptors in the production of these responses. 6. In the more rostral vestibular
      nuclei, responses to vestibular and neck rotation are most often antagonistic, so
      that head rotation results in little or no response. This is not the case in the
      caudal areas of the vestibular nuclei, where less than half the neurons tested
      displayed antagonistic behavior. Further experiments are required to put the neck
      projection to the caudal vestibular nuclei in a functional context.

PMID- 8867133
TI  - Cable properties of cultured hippocampal neurons determined from sucrose-evoked
      miniature EPSCs.
AB  - 1. The passive cable properties of rat hippocampal neurons in dissociated culture
      were studied using focal application of hypertonic solution to locally elicit
      miniature excitatory postsynaptic currents (mEPSCs) on the soma and dendrites.
      Neurons were filled with Lucifer yellow and portions of their dendritic trees
      were measured. 2. The average mEPSC measured at the soma appeared smaller and
      slower as the site of sucrose application was made more distal. Normalizing to a
      1-micron diam dendrite, the mean mEPSC peak amplitude and charge was reduced e
      fold in 170 and 1,000 microns, respectively, and the mean mEPSC decay time
      constant was increased e-fold in 150 microns. However, for any particular sucrose
      site, individual mEPSCs varied widely in their amplitudes and time courses. Plots
      of individual peak amplitudes versus half-width or rise time showed much overlap
      for mEPSCs originating from sites as much as 100 microns apart. This suggests
      that use of such plots to estimate the electrotonic location of synaptic currents
      is highly prone to error. 3. Averaged mEPSCs recorded when applying sucrose at
      the soma were poorly fitted by an alpha function but were well-described by an
      equation of the form mxh, where m incorporates a rise-time constant tau 1 and h a
      decay time constant tau 2. Averaged fits to mean mEPSCs elicited at the somas of
      five cells gave (mean +/- SE): peak conductance = 832 +/- 126 pS, tau 1 = 0.29 +/
      0.06 ms, tau 2 = 3.03 +/- 0.24 ms, x = 4.7 +/- 0.7. 4. For three cells, the
      entire dendritic branch to which sucrose was applied was measured and used to
      construct a passive cable model. The specific membrane resistance (Rm) and
      intracellular resistivity (Ri) were varied systematically in the model (assuming
      membrane capacitance Cm = 1 microF/cm2) to search for the best agreement between
      the mean mEPSCs and the model. Optimal Rm was found to lie in the range 20-30 k
      omega cm2, Ri in the range 100-200 omega cm. 5. These results confirm those
      obtained by other methods and emphasize the considerable cable filtering of fast
      electrical events in cultured hippocampal neurons.

PMID- 8867134
TI  - Sweet taste transduction in hamster: sweeteners and cyclic nucleotides depolarize
      taste cells by reducing a K+ current.
AB  - 1. The gigaseal voltage-clamp technique was used to record responses of hamster
      taste receptor cells to synthetic sweeteners and cyclic nucleotides. Voltage
      dependent currents and steady-state currents were monitored during bath exchanges
      of saccharin, two high-potency sweeteners, 8-chlorophenylthio-adenosine 3',5'
      cyclic monophosphate (8cpt-cAMP), and dibutyryl-guanosine 3',5'-cyclic
      monophosphate (db-cGMP). 2. Of the 237 fungiform taste cells studied, only one in
      eight was sweet responsive. Outward currents, both voltage-dependent and resting,
      were reduced by all of the sweeteners tested in sweet-responsive taste cells,
      whereas these currents were unaffected by sweeteners in sweet-unresponsive taste
      cells. 3. In every sweet-responsive cell tested, 8cpt-cAMP and db-cGMP mimicked
      the response to the sweeteners, but neither nucleotide elicited responses in
      sweet-unresponsive cells. Thus there was a one-to-one correlation between sweet
      responsivity and cyclic nucleotide responsivity. 4. Sweet responses showed cross
      adaptation with cyclic nucleotide responses. This indicates that the same ion
      channel is modulated by sweeteners and cyclic nucleotides. 5. The sweetener- and
      cyclic nucleotide-blocked current had an apparent reversal potential of -50 mV,
      which was close to the potassium reversal potential in these experiments. In
      addition, there was no effect of sweeteners and cyclic nucleotides in the
      presence of the K+ channel blocker tetraethylammonium bromide (TEA). These data
      suggest that block of a resting, TEA-sensitive K+ current is the final common
      step leading to taste cell depolarization during sweet transduction. 6. These
      data, together with data from a previous study (Cummings et al. 1993), suggest
      that both synthetic sweeteners and sucrose utilize second-messenger pathways that
      block a resting K+ conductance to depolarize the taste cell membrane.

PMID- 8867135
TI  - Docosahexaenoic acid reduces GABA response in substantia nigra neuron of rat.
AB  - .1. The effects of docosahexaenoic acid (DHA) on gamma-aminobutyric acid (GABA)
      response (IGABA) were investigated on the neuron acutely dissociated from rat
      substantia nigra (SN), with the use of patch recordings in a whole cell mode. 2.
      DHA (5 x 10(-6) M) reduced bicuculline-sensitive GABA (10(-4) M) current by 50.3
      +/- 13.1% (mean +/- SE) at a holding potential (Vh) of -40 mV under voltage
      clamp. 3. The GABA concentrations for the half-maximum and threshold of IGABA
      were not altered by the presence or absence of 5 x 10(-6) M DHA in the external
      solution. 4. The decrease of 10(-4) M IGABA, following the peak during GABA
      application, was more rapid in the presence of 5 x 10(-6) M DHA than in its
      absence. The time constants for IGABA decay were significantly different between
      the two conditions. 5. DHA reduced the IGABA and the glycine-induced response
      (Igly) in a concentration-dependent manner. On the contrary, DHA potentiated the
      aspartate-induced response (Iasp) in a concentration-dependent manner, suggesting
      that DHA influences the activity of chloride channels but does not exhibit a
      nonspecific blocking effect on any ionic channel. 6. The application of
      thimerosal did not affect the reduction of IGABA by DHA, suggesting it unlikely
      that DHA reduces the IGABA by binding to phospholipids or triglycerides and
      altering the lipid environment around the chloride channel. 7. Arachidonic acid
      (AA) also reduced the IGABA in a manner similar to DHA. Docosapentaenoic acid
      (DPA) reduced the IGABA less potently than DHA. Other polyunsaturated and
      saturated fatty acids, such as docosatrienoic acid, docosatetraenoic acid,
      palmitic acid, and oleic acid, had very little or no effect on the IGABA. 8. DHA,
      as well as AA, may play an important role in modulating neuronal excitability by
      reducing the IGABA and Igly, and potentiating N-methyl-D-aspartate receptor
      mediated responses in the SN.

PMID- 8867136
TI  - In vitro brain slice studies of the rat's dorsal nucleus of the lateral
      lemniscus. III. synaptic pharmacology.
AB  - 1. The synaptic pharmacology of the dorsal nucleus of the lateral lemniscus
      (DNLL) of the rat was investigated in a brain slice preparation of the auditory
      midbrain. The brain slice was cut in the coronal plane and placed in a small
      recording chamber where warm, oxygenated saline was continuously perfused over
      and underneath the tissue. Intracellular recordings were made with glass
      microelectrodes filled with 4 M potassium acetate. Synaptic potentials were
      elicited by electrical stimulation of the lateral lemniscus or commissure of
      Probst and pharmacological effects were tested by bath application of amino acid
      agonists and antagonists. 2. The cells in DNLL were challenged with the
      excitatory amino acid (EAA) agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA), N-methyl-D-aspartic acid (NMDA) in 0 Mg2+, and L
      glutamate. Each of these caused a depolarization of the cell membrane, a
      reduction in cell membrane resistance, and the onset of spontaneous firing. 3.
      Short-latency excitatory postsynaptic potentials (EPSPs) were evoked by
      stimulation of the lateral lemniscus in 77% of the neurons tested. The mean
      latency to initial depolarization was 0.9 ms. A single spike with relatively
      constant latency (mean 1.5 ms) was typically elicited when the strength of
      lemniscal stimulation was increased. A longer-latency EPSP (mean 2.9 ms) was seen
      in 34% of the neurons tested either with the slice in normal saline or after
      pharmacological block of the earlier, short-latency EPSP. The long-latency EPSP
      was followed by a single spike of multiple spikes with highly variable latencies
      (range 3.2-24 ms). In 28% of the neurons tested, both early and late EPSPs were
      observed in response to stimulation of a single location on the lateral
      lemniscus. 4. Stimulation of the commissure of Probst elicited short-latency
      EPSPs (mean 0.9 ms) in 37% of the neurons tested. Longer-latency EPSPs (mean 3.0
      ms) were found in only 3% of the neurons in response to commissural stimulation.
      5. The nonspecific EAA antagonist kynurenic acid blocked both short-and long
      latency EPSPs evoked by either lemniscal or commissural stimulation. The non-NMDA
      antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), at very low
      concentrations, blocked the short-latency EPSPs but had no effect on the longer
      latency EPSPs. The short-latency EPSPs were unaffected by the NMDA antagonist D,L
      2-amino-5-phosphonovaleric acid (APV). In contrast, the longer-latency EPSPs were
      blocked by APV, but never by CNQX. 6. DNLL neurons were affected by the
      inhibitory amino acid agonists gamma-aminobutyric acid (GABA) and glycine. The
      membrane resistance of the neurons was decreased by GABA and glycine in a
      solution of either normal or calcium-free saline in a concentration-dependent
      manner. 7. Inhibitory postsynaptic potentials (IPSPs) were elicited by
      stimulation of the lateral lemniscus in 53% of the neurons and the commissure of
      the Probst in 18% of the neurons tested. The mean latencies were 1.0 and 0.9 ms,
      respectively. The reversal potentials of the IPSPs were around -70 mV. 8. The
      IPSPs evoked by stimulation of the lateral lemniscus were blocked by the glycine
      receptor antagonist strychnine, but not by the GABA receptor antagonist
      bicuculline, whereas the IPSPs elicited by stimulation of the commissure of
      Probst were blocked by bicuculline but not strychnine.

PMID- 8867137
TI  - Neuronal responses in cat primary auditory cortex to electrical cochlear
      stimulation. II. Repetition rate coding.
AB  - 1. Responses of neurons in primary auditory cortex (AI) of the barbiturate
      anesthetized adult cat were studied using cochlear stimulation with electrical
      and acoustic stimuli. Neuronal responses to acoustic stimulation with brief
      biphasic clicks of the ear ipsilateral to the studied cortical hemisphere were
      compared with those evoked by electrical stimulation of the contralateral cochlea
      with brief biphasic electrical pulses delivered via a feline cochlear prosthesis.
      The contralateral ear was deafened immediately before implantation of the
      cochlear prosthesis. The feline cochlear prosthesis consisted of four bipolar
      electrode pairs and was placed in the scala tympani. Two bipolar electrode
      conditions were used for stimulation: one near radial pair with electrode spacing
      of 0.25-0.5 mm, and one longitudinal pair with electrode spacing of approximately
      6 mm. 2. The firing rates obtained from single- and multiple-neuron recordings
      were measured as a function of stimulus repetition rate of electrical and
      acoustic pulses. From period histograms over a recording interval of 1,000 ms,
      the driven firing rate to repetition rates from 2 to 38 Hz was obtained and
      repetition rate transfer functions (RRTFs) were constructed. The RRTFs were
      characterized as low-pass or band-pass filters and several descriptors were
      obtained, such as the repetition rate producing the highest driven activity, high
      and low cutoff frequencies 6 dB below maximum firing rate, and maximum firing
      rate. 3. For a given neuron, the main characteristics of cortical RRTFs obtained
      with electrical and acoustic cochlear stimulation were quite similar. However,
      some small but statistically significant differences in the best repetition rate,
      cutoff frequencies, and maximum firing rate could be observed between the
      different stimulation modes. The proportion of band-pass RRTFs was larger for
      electrical stimulation (57%) than for acoustic stimulation (41%). The high cutoff
      frequencies for electrical stimulation were slightly but consistently higher than
      for acoustic RRTFs of the same neuron and the maximum firing rate for electrical
      stimulation was significantly higher than that evoked by ipsilateral acoustic
      stimulation. 4. The entrainment of cortical neurons to electrical and acoustic
      pulses was determined and entrainment profiles were constructed. For a given
      neuron, electrical entrainment profiles showed higher cutoff frequencies than
      with acoustic stimulation when judged with a fixed entrainment criterion of 0.25
      spikes per event. The maximum entrainment seen for electrical stimulation was
      approximately 20% higher than seen for the same neuron with acoustic stimulation.
      5. Correlation analysis of repetition coding and latency parameters revealed
      several relationships between these response aspects. Most prominent among them
      was a significant correlation between measures of the response latency and
      estimates of the ability to follow temporal repetitions for acoustic as well as
      electrical conditions. 6. Parametric and comparative evaluations of cortical
      responses to acoustic and electrical cochlear stimulation support the conclusion
      that the temporal resolution seen in cortical neurons is largely a consequence of
      central processing mechanisms based on cell and circuit properties and to a
      lesser degree a consequence of particular spatial and temporal peripheral
      excitation patterns. The slightly higher temporal resolution found for the
      electrical stimulation modes suggests that the temporally highly coherent
      electrical stimulation appears to engage, in a more effective manner, the
      excitatory/inhibitory mechanisms contributing to the response in AI than acoustic
      click stimulation with less temporal coherence. (ABSTRACT TRUNCATED)

PMID- 8867138
TI  - Projection neurons of the lateral amygdaloid nucleus are virtually silent
      throughout the sleep--waking cycle.
AB  - 1. Amygdala neurons were recorded extracellularly during the sleep-waking cycle
      in chronically implanted cats. Neurons were identified as projection cells when
      they could be antidromically invaded from the perirhinal and/or entorhinal
      cortices. 2. In contrast with other nuclei of the amygdala, few spontaneously
      active neurons were encountered in the lateral nucleus. However, when hunting
      stimuli were applied to the parahippocampal cortices, we noticed the presence of
      numerous projection cells that would have otherwise remained undetected because
      they had little or no spontaneous activity. 3. In the states of waking, slow-wave
      sleep, and paradoxical sleep, the discharge rate of antidromically invaded
      neurons averaged 0.09 +/- 0.07 Hz (mean +/- SE) with 82% of cells firing at <
      0.01 Hz in all states. However, they transiently increased their firing rate when
      cats were presented complex sensory stimuli, which apparently were specific to
      each cell. In contrast to projection cells, spontaneously active neurons of the
      lateral nucleus that could not be backfired from the parahippocampal cortices had
      an average firing rate of 4.34 +/- 1.15 Hz with 38% of cells firing at > or = 6
      Hz in at least one state. 4. These results on the extremely low firing rates of
      identified projection cells suggest that previous extracellular studies of
      lateral amygdaloid neurons were biased toward a class of spontaneously active
      cells which probably includes local-circuit cells.

PMID- 8867139
TI  - Responses in area V4 depend on the spatial relationship between stimulus and
      attention.
AB  - 1. We studied the spatial interaction between stimulus and attention in macaque
      area V4. Monkeys were required to fixate a small spot while continuously
      attending to a ring-shaped target within a large array of identical rings.
      Meanwhile, the response of the V4 cell under study was tested by flashing
      behaviorally irrelevant bar stimuli in the cell's classical receptive field
      (CRF). The location of the attended ring was varied across four positions
      surrounding the CRF, and the location of the bar stimulus was varied across five
      positions spanning the CRF. 2. Response strength depended on two aspects of the
      spatial relationship between the stimulus driving the cell (the bar) and the
      position of attention (the target ring). First, for 49% of the cells studied,
      responses were greater for bar stimuli near the attended ring; i.e., the
      receptive field profile shifted toward the attentional focus. Second, for 84% of
      the cells, the overall response level depended on the direction in which
      attention lay relative to the stimulus in the CRF (e.g., to the left, right,
      above, or below). 3. This study confirms a key prediction of spatial models of
      attention, which postulate enhanced processing of all stimuli near the
      attentional focus. It also introduces the novel finding that responses are
      influenced by the relative direction of attention. This result indicates that
      area V4 carries information about the spatial relationship between visual stimuli
      and attention.

PMID- 8867140
TI  - Comparison of supercritical fluid extraction and solvent extraction of twenty-two
      organochlorine pesticides from eggs.
AB  - The recoveries of twenty-two organochlorine pesticides spiked in egg samples were
      extracted by supercritical fluid extraction (SFE) using carbon dioxide and
      solvent extraction using acetonitrile were compared. The extracts were cleaned up
      with C18 and Florisil SPE columns. At 0.1 ppm spike level, the recoveries were 52
      - 100% by SFE and 53 - 93% by solvent extraction. The limits of detection
      calculated at 0.01 ppm spike level were 0.072 - 0.006 ppm for SFE and 0.06 -
      0.006 ppm for solvent extraction. Both methods show improvement in sample
      preparation time and solvent consumption from the existing Soxhlet extraction
      method.

PMID- 8867141
TI  - Searching for information on toxicological data of chemical substances in
      selected bibliographic databases--selection of essential databases for
      toxicological researches.
AB  - By using information from printed and online database guides, 18 online
      bibliographic databases (BD), which cover literature on toxicology were selected
      from 5 hosts. A search for literature containing information on three selected
      chemicals was carried out with each of the databases, and the number of documents
      relevant to toxicology found in them was compared by computer-assisted analysis.
      Some databases yielded very little information pertinent to toxicology, while
      others provided a considerable amount. In addition, the databases contained
      numerous duplicates (references common to more than one database). Most of the
      relevant documents could be obtained using only 8 of the 18 BDs selected. These
      databases are: Biosis Previews (BIOSIS), Chemical Abstracts (CA), Chemical Safety
      Newsbase (CSNB), Excerpta Medica (EMBASE), National Institute for Occupational
      Safety and Health (NIOSH), Scisearch, Toxicology Information Online (TOXLINE) and
      the former Toxicology Literature (TOXLIT).

PMID- 8867142
TI  - A growth inhibition test with sewage bacteria--results of an international ring
      test 1995.
AB  - A bacterial toxicity test method using the determination of growth inhibition of
      sewage bacteria within an incubation period of 6 hours will be standardized at
      ISO. A ring test was performed with 24 participants using 3.5-dichlorophenol and
      potassium cyanide as test substances. The analysis of the test results showed
      that the method is very accurate and appropriate for determining the bacterial
      toxicity of chemical compounds. Due to the results obtained 3.5-dichlorophenol
      was proposed as a reference substance.

PMID- 8867143
TI  - Inactivation of Escherichia coli by photocatalytic oxidation.
AB  - The inactivation of Escherichia coli (E.coli) was studied in presterilized
      surface water sample using titanium dioxide as the photocatalyst under
      irradiation of BLF Fluorescent lamps. Inactivation of E.coli (10(3) CFU/mL) was
      achieved in 60 min in the presence of 1.0 mg TiO2/mL. Photocatalytic inactivation
      data was evaluated in terms of first order rate equation N/N0 = e (-kIt). The
      reaction rate constant k, 1.22*10(-2)(mW min/cm2)-1 was calculated.

PMID- 8867144
TI  - A research to develop a predicting system of mammalian subacute toxicity. I.
      Prediction of subacute toxicity using the biological parameters of acute
      toxicities.
AB  - Predicting equations of subacute toxicity were developed by analyzing rat acute
      and subacute toxicity data of 56 chemicals of various structures. Minimum or 10%
      effect level in acute or subacute toxicity was estimated as a "biological
      parameter". Good regression equations were established between the geometrical
      means ("combined parameters") of any two of the parameters of acute and subacute
      toxicities and introduction of log P to the equations improved the correlations
      with a statistically significant multiple regression coefficient. The lowest
      predicted effect level of the subacute toxicity, which is selected from the data
      calculated by the above several correlations, can predict the upper limit of the
      no observed effect level. In recent years, for research and development of new
      chemical substances, it becomes one of the important factors that these have a
      lower environmental load in nature. Eventually, it becomes essential to evaluate
      not only their acute effects on human or environments, but also their chronic
      influences when they are to be exposed for a long period of time, and the cost
      for such verification is becoming a breaking factor for research and development.
      Thus, the development of a new technique which estimates the environmental load
      of a chemical substance including toxic effects on human with lower cost is now
      being attempted. For example, the development of in vitro new alternative methods
      using cultured cells, the utilization of a data base or software which relates
      mammalian and environmental toxicities and so on are internationally carried
      forwards. As for the latter, quantitative structure-activity relationship (QSAR)
      techniques have been applied practically to decide appropriate toxicity tests
      needed for regulatory purposes by EPA/TSCA, ITC/TSCA and FDA/FDAA in the USA. In
      addition, it was concluded recently in a joint meeting of EU and US-EPA that the
      approach by QSAR techniques was useful to specify the new chemical substances
      which are to be required toxicological examinations. In these QSAR techniques,
      however, while there are some considerations about common mechanisms of toxicity
      among chemicals with a similar structure (Congeneric chemicals, Congeners) for
      establishing of correlation formulas, for chemicals with various structures (Non
      congeneric chemicals, Non-congeners) there often lack such common considerations.
      In addition, biological or physiological factors which are basic toxic indices
      are often ignored. In a previous study, we researched acute and subacute oral
      toxicities of industrial common chemicals in rats and reported the followings; 1)
      their subacute toxicological spectrum in target organs/tissues and morphologic
      changes was very limited and specific, 2) the important targets were liver,
      kidneys, blood (spleen) and stomach and these are considered the sites of
      dominant exposure due to the kinetics of chemical substances, 3) the
      morphological changes were hepatocellular hypertrophy, deposition of substance in
      renal tubules, extramedullary hematopoiesis in spleen and mucous lesion in
      stomach, and these are implying adaptation such as induction of drug-metabolizing
      enzymes, overload to renal function, anemia from erythrocyte destruction, and
      direct reaction, respectively, 4) there seems to occur a series of direct and
      adaptive reactions to exclude the "foreign compounds" which do not show any
      specific biological activities, 5) it is also considered that there is a
      possibility to establish a correlation between toxicological findings or target
      organs/tissues of both acute and subacute toxicities by their continuity.
      Therefore, in the present study, a predicting equation of subacute (28-day
      repeated dose) toxicity is attempted to develop from acute (single dose) toxicity
      data by considering both common mechanisms and biological factors for non
      congeneric industrial chemical substances.

PMID- 8867145
TI  - A research to develop a predicting system of mammalian subacute toxicity. II.
      Single dose detailed toxicity studies.
AB  - "Single dose detailed toxicity study" in rats was conducted with 6 chemical
      substances to establish a predicting system of subacute toxicity of non
      congeneric industrial chemicals. In the detailed examinations, new and previously
      reported biological parameters were developed and utilized for the establishment
      and confirmation of the correlations for both qualitative and quantitative
      prediction of target organs and effects in repeated dose toxicity studies of non
      congeners; the new parameters were concerned with liver, kidneys and blood and
      the established relating equations for prediction had a correlation coefficient
      of 0.83 (liver), 0.49 (kidneys) and 0.94 (blood), while the old parameters
      effectively confirmed the previous correlations. The serial changes in the study
      gave a biological explanation to the established relationships between acute and
      subacute toxicities in terms of extrapolation.

PMID- 8867146
TI  - The use of toxic equivalency factors in assessing occupational and environmental
      health risk associated with exposure to airborne mixtures of polycyclic aromatic
      hydrocarbons (PAHs).
AB  - The health risk associated with inhalatory exposure to PAHs either in the
      occupational atmosphere or in outdoor air is commonly assessed on the basis of
      benzo(a)pyrene (BaP) concentrations in air. The PAH-related health risk is
      calculated with the help of epidemiological data from coke oven workers. The
      proportion of individual carcinogenic PAHs to BaP has been shown to vary in
      different environments by one to two orders of magnitude. Despite this, the unit
      risk value for BaP derived from epidemiological studies of coke oven workers is
      used for risk estimation of these environments. Toxic equivalency factors (TEFs)
      for individual PAHs were used to estimate human health risk associated with
      inhalatory exposure to PAHs. Given the uncertainties involved in risk assessment
      in general, a variability of risk estimation for PAH mixtures based on the toxic
      equivalency factor concept by a factor 2.6 is low and rather unreasonably
      precise. This underlines the importance of BaP as a surrogate compound of a PAH
      mixture.

PMID- 8867147
TI  - Levels of selected ortho and non-ortho polychlorinated biphenyls in UK retail
      milk.
AB  - Nineteen pooled samples of retail cow's milk were analysed for ortho (PCBs 28,
      52, 101, 118, 138, 153 and 180) and non-ortho (PCBs 77, 126 and 169)
      polychlorinated biphenyls. Concentrations of individual congeners in whole milk
      were in the ranges 2 to 95 ng/kg for ortho substituted PCBs (51 to 2440 ng/kg
      fat) and 0.05 to 0.6 ng/kg for non-ortho substituted PCBs (1.3 to 15.4 ng/kg
      fat). These values provide a preliminary estimate of background contamination
      levels for polychlorinated biphenyls in UK milk. Results expressed in TEQs, using
      the recently proposed WHO/IPCS TEFs, averaged 0.06 ng TEQ/kg whole milk.

PMID- 8867148
TI  - Comparisons of heavy metal concentration of grass carp (Ctenopharyngodon idella
      Cuv. et Val.) in a shallow eutrophic lake and a fish pond (possible effects of
      food contamination).
AB  - Nickel, Cu, Zn, Cd, Pb and Hg concentrations were determined in gills, liver,
      kidney, muscle and gut of grass carp (Ctenopharyngodon idella Cuv. et Val.)
      collected from Lake Balaton (Hungary) and from a fish pond of a fish farm nearby.
      The body weight normalised heavy metal concentrations in different organs/tissues
      were compared and ordered for both Lake Balaton and the fish farm. Metal
      concentrations, in most cases were highest in kidney or in liver, and lowest in
      muscle or in gut. Nickel concentration was lower in liver, muscle and gills of
      fish from Lake Balaton. We suppose that an earlier sewage water load resulted in
      the higher Ni levels in grass carp from the fish pond. Mercury concentration was
      also lower in the gut of grass carp from Lake Balaton, but the other organs
      showed higher concentrations at this location. Our results suggest that the
      accumulation mechanism of Hg may be different from other metals in non-predatory
      fish species. Mercury uptake from food may be dominant for all fish species, but
      'biomagnification' becomes obvious only in the case of predatory species.

PMID- 8867149
TI  - Inhibition of acetylcholinesterase activity as effect criterion in acute tests
      with juvenile Daphnia magna.
AB  - In this work we investigated the possibility of using the enzyme
      acetylcholinesterase (AChE) activity in Daphnia magna homogenates, both in vivo
      and in vitro conditions, as a specific method for rapid toxicity evaluations. The
      results from in vivo and in vitro AChE inhibition tests were compared with 48
      hours EC50 values obtained in conventional acute bioassays. EC50 values from in
      vivo AChE inhibition tests were: 2.4 micrograms/l for parathion, 0.2 microgram/l
      for paraoxon; DCA and cadmium at the concentrations tested had no effects on
      enzyme activity. I50 values were 764 micrograms/l for parathion, 0.08
      micrograms/l for paraoxon and 3367 micrograms/l for cadmium; DCA did not affect
      AChE activity measured in in vitro conditions. EC50 values from conventional
      acute tests were: 2.2 micrograms/l for parathion, 0.2 microgram/l for paraoxon,
      163 micrograms/l for DCA and 9.5 micrograms/l for cadmium. Our results indicated
      that the in vivo AChE inhibition test is selective, being very sensitive to
      detect toxicity of the organophosphates tested. The in vitro AChE inhibition
      assay is less time consuming, requires less human effort and produces less toxic
      waste than conventional acute bioassays and the in vivo AChE inhibition test.
      However, it does not take into account the effect of the metabolization of the
      toxicants inside live organisms; since the organophosphate metabolism may be
      activative or degradative, the toxic potential of the parent compound may be
      under or over evaluated in in vitro conditions.

PMID- 8867150
TI  - Accumulation of extractable organic halogens (EOX) by the freshwater mussel,
      Anodonta cygnea L., exposed to chlorine bleached pulp and paper mill effluents.
AB  - Freshwater mussels, Anodonta cygnea L., were collected in a lowly polluted area
      in north-eastern France, and exposed during 28 days at three sites up and
      downstream of a chlorine bleached pulp and paper mill effluent Water, sediment
      and mussel samples were collected at regular intervals and analyzed for
      halogenated organic residues using the sum parameters AOX (Adsorbable Organic
      Halogen) and EOX (Extractable Organic Halogen). The survey of the water showed a
      chronic contamination by organic halogens of the water and the sediment
      downstream of the pulp and paper mill sewer. Mussels exposed upstream of the mill
      showed no significant variation of their EOX tissue concentration. In contrast,
      progressive accumulation of EOX occurred with the exposure time in mussels
      exposed downstream of the mill. No steady state of the EOX concentration was
      observed after four weeks of exposure.

PMID- 8867151
TI  - On the importance of hydroxyl groups in the polar head-group of nonionic
      surfactants and membrane lipids.
AB  - In this review properties of natural membrane lipids and surfactants synthesized
      from natural substances, such as paraffin chain alcohols and carbohydrates, are
      compared with those of synthetic surfactants of the polyoxyethylene type. Special
      attention is paid to the characteristic solution properties of nonionic
      surfactants with hydroxyl groups as the hydrophilic moiety, including alkyl
      glyceryl ethers and alkyl glucosides and maltosides, which are compared with
      those with oxyethylene groups. The major properties of the hydrophilic moiety are
      lipophobicity and hydrophilicity. Lipophobicity is an important property of oil
      soluble surfactants, in particular for the polyoxyethylene alkyl ether type of
      surfactants where a too high lipophobicity may result in solubility in water.

PMID- 8867152
TI  - [Cataract operation with the 7 mm clear cornea incision].
AB  - Cataract surgery can be combined with the correction of high preoperative
      astigmatism by using a corneal tunnel incision in the steep meridian. We examined
      37 patients (mean age 70 years) with cataract and a mean preoperative astigmatism
      of 3.6 D (2.0-4.75 D). A 7-mm clear corneal incision was made for
      phacoemulsification and thus a reduction in the astigmatism was achieved. The
      mean induced astigmatism was 3.6 D (SD 1.6 D minium 0.8 D, maximum 7.5 D) on the
      first postoperative day and 2.7 D (SD 0.9 D, minimum 1.6 D, maximum 4.9 D) after
      10 months. By modification of the incision technique with a trapezoidal corneal
      incision and a single radial suture the wound closure was more stable, but the
      astigmatic correction did not change significantly compared to the results after
      the original 7-mm clear corneal incision technique.

PMID- 8867153
TI  - [Self-closing corneoscleral tunnel incision in cataract surgery].
AB  - Self-sealing wound construction in the cataract surgery can be performed
      sclerally or corneally (clear corneal incision). Each technique has different
      advantages and disadvantages concerning wound preparation, induced astigmatism,
      and wound closure stability with rising intraocular pressure. The corneoscleral
      tunnel incision could have the advantages of both scleral and corneal incisions.
      PATIENTS AND METHODS: We performed a trapezoid corneoscleral tunnel incision in
      108 cases. The incision has a width of 7 mm and a radial length of 1.5-2 mm. In
      39 patients the incision was performed at the 12 o'clock position. A lateral
      approach was made in 69 patients because astigmatism against the rule
      preoperatively. The wound closure was achieved by elevation of IOP to 30-40 mmHg
      without suture, as in the no-stitch technique. RESULTS: In comparison to the 7-mm
      corneal incision, the corneoscleral incision had a higher wound stability. Even
      external pressure at the wound location could not provoke leaking. The induced
      astigmatism was examined up to 4 months postoperatively. The mean astigmatism was
      around 1.2 D for the superior wound preparation versus 0.5 D for the lateral
      approach. CONCLUSION: The corneoscleral tunnel incision can be used routinely.
      The following advantages can be stated: (1) moderate cauterisation, (2) easy and
      reliable wound preparation, (3) high wound stability even with 7-mm incision, (4)
      wound opening completely covered by conjunctiva postoperatively, (5) clinically
      tolerable induced astigmatism. This technique can also be used if an astigmatism
      up to 1.5 D exists preoperatively.

PMID- 8867154
TI  - [Vector analysis of surgically-induced astigmatism in cataract operation with 4
      tunnel incision techniques].
AB  - Evaluation of astigmatism induced by cataract surgery requires the calculation of
      surgically induced astigmatism using vector analysis. This method was performed
      for four tunnel-incision techniques and compared with the results of computer
      assisted videokeratoscopy. METHODS: Phacoemulsification with IOL implantation was
      performed in 59 eyes using four different incisions (4- or 5- to 6-mm scleral
      tunnel and 4- or 5.5-mm clear cornea). Surgically induced astigmatism was
      calculated by vector subtraction using the formulas of Retzlaff. In addition,
      corneal topography was performed and astigmatism was calculated within three
      concentric corneal zones (3 mm, 3-5 mm, 5-7 mm). RESULTS: Surgically induced
      astigmatism after a 4-mm scleral tunnel incision was 0.55 D (pre-op 0.58 D, post
      op 0.72 D), the 5-6-mm incision induced 0.89 D (pre-op 0.97 D and post-op 1.02
      D). The 4-mm clear cornea incision induced 2.00 D (from 0.89 D to 1.56 D), the
      5.5-mm corneal incision, performed in the steepest meridian to reduce preexisting
      astigmatism, induced 3.57 D; pre-op 3.38 D, post-op 2.09 D. Corneal topography
      revealed a slight increase in astigmatism within all corneal zones (4-mm scleral
      tunnel: 0.26 D, 5-6-mm scleral tunnel: 0.36 D and 4-mm clear cornea incision:
      0.22 D). After a 5.5-mm clear cornea incision, however, astigmatism of the
      central 3-mm zone was reduced by 1 D, while astigmatism of the 5-7 mm zone
      increased by 0.22 D. CONCLUSION: The 4- and 5- to 6-mm scleral tunnel as well as
      the 4-mm clear cornea incision were shown to be nearly astigmatism-neutral. The
      5.5-mm clear cornea incision reduced astigmatism of the central cornea by about
      35%, but induced irregular astigmatism in the periphery.

PMID- 8867155
TI  - [The True-Vista bifocal intraocular lens. Current results of the European
      multicenter study].
AB  - In a prospective multicenter study we evaluated vision with the True Vista
      bifocal IOL. At 12-14 months after operation. 391 patients ("best cases") were
      available for follow-up. Without (with) correction, 14.4% (37.9%) had a distance
      acuity of 20/20 or better, 28% (69.6%) had 20/25 or better, 70% (96.9%) had 20/40
      or better, and 30% (3.1%) had a distance acuity of less than 20/40. Near acuity
      without (with) correction was 20/20 or better in 18.7% (57.5%), 20/25 or better
      in 42.9% (80.8%), 20/40 or better in 84% (97.5%), and less than 20/40 in 16%
      (2.5%). Our results demonstrate that corrected distance and near acuity with the
      True Vista bifocal IOL is good. However, due to surgically induced astigmatism
      and inaccuracies of IOL power calculation, uncorrected acuities are still
      disappointing. Thus, when implanting bifocal IOLs, careful patient selection,
      control of astigmatism and IOL power calculation seems crucial.

PMID- 8867156
TI  - [Suitability of polyvinylpyrrolidone (PVP) as a substance for hydrogel
      intraocular lenses].
AB  - Conventional PMMA intraocular lenses (IOLs) have been shown to restore vision
      successfully after cataract surgery, but have been associated with complications
      such as decentration, destruction of intraocular tissue, and posterior capsule
      opacification. Expansile IOLs based on cross-inked polyhydroxyethylmethacrylate
      (PHEMA) also undergo chemically induced hydrolysis, polymer leaching and gel
      fragmentation. The focus of this research is to prepare and characterize hydrogel
      IOLs prepared from PVP using gamma-irradiation. METHODS: Hydrogels were prepared
      from aqueous solutions of PVP by free radical polymerization as a function of
      gamma-irradiation dose (0.5 x 106 to 2.5 x 106 rad), PVP concentration (4% to 16%
      w/v), molecular weight (MW) (10 x 103 to 360 x 103 Da), and blending with low and
      high MW PVP. Viscometric analysis, swelling characterization studies, and polymer
      leaching studies were carried out to access network formation. In addition
      changes in lens geometry in an animal model were measured in response to
      cycloplegic eyedrops. RESULTS: Cross-linking efficiency was greatest with an
      initial MW of 360 x 103 Da and lowest with an initial MW of 10 x 103 Da. The time
      to reach equilibrium from the glassy state and the degree of swelling in saline
      decreased with increasing gamma-irradiation dose and increased with concentration
      of PVP and blending of low and high MW PVP. The equilibrium water content ranged
      from 90 to 98% (w/w). Eighty-five percent of the equilibrium dimensions could be
      achieved within 90 min. Gravimetric analysis and HPLC indicate that the amount of
      PVP that is not incorporated into the network ranges from 0.25% to 6% (w/w). This
      was inversely related to the gamma-irradiation dose. The MW of the leached
      samples was estimated to be greater than 10 x 103 Da in all cases. CONCLUSIONS:
      PVP hydrogel IOLs prepared by gamma-irradiation have advantages in terms of
      chemical stability, high water content, and ease of preparation. They may not
      need further purification or sterilization prior to implantation. In addition,
      they may allow for accommodation. No comments can be made regarding the
      biocompatibility, long-term stability, or optical quality at this time.

PMID- 8867157
TI  - [6 months results of a randomized multicenter study comparing 2 silicone
      intraocular lenses with a PMMA intraocular lens].
AB  - Of the 1,158 eyes operated on for cataracts in 1993, 815 were implanted with two
      types of silicon PC IOLs (90 D, Adatomed or C 10, Chiron) or a one-piece PMMA IOL
      according to a randomized scheme. These eyes were followed up 4-6 months after
      surgery. More than 90% of all eyes showed a best-corrected VA of 20/40 or better,
      and the amount of postoperative complications was low and equally distributed
      following implantation of all three types of IOLs.

PMID- 8867158
TI  - [Clinical secondary cataract evaluation in pseudophakic eyes. Method and
      reproducibility].
AB  - INTRODUCTION: According to the literature, the frequency of secondary cataract
      reported following different studies of posterior chamber intraocular lens (IOL)
      implantation varies widely. The nonstandardized definition of a clinically
      significant secondary cataract is one of the reasons for this. We present a
      morphological scoring system for secondary cataract that does not require visual
      acuity testing. PATIENTS AND METHODS: Following dilatation of the pupil
      standardized photographs of the pseudophakic anterior segments were obtained by
      means of a Zeiss photoslit-lamp (model 40 SL/P). The posterior capsule
      opacification (PCO) was scored by evaluating retroillumination photographs. The
      individual PCO score was calculated by multiplying the density of the
      opacification (graded from 0 to 4) by the area involved behind the IOL optic
      (calculated between 0 and 1). In order to evaluate the reliability of the
      morphological scoring system, in experiment A six observers examined photographs
      of five eyes each (interindividual reliability), and in experiment B the same
      observers each scored the PCO of three eyes on 5 different days (intraindividual
      reliability). In experiment C seven different pairs of photographs taken on the
      same day were scored for PCO by the same observer (influence of photographic
      variations). RESULTS: Morphological PCO scores were reliable. With PCO scoring
      ranging from 0 to 4, interindividual reliability revealed standard deviations
      between 0.08 and 0.25. The intraindividual reliability showed standard deviations
      between 0.06 and 0.19 of any individual PCO score. The standard deviation was
      0.12 when different photographs of the same eye were scored. CONCLUSIONS: When
      the entire area behind the IOL optic is evaluated a larger area of the posterior
      capsule is taken into account than during testing of visual acuity alone. This
      method revealed high reliability and only minimal investigator-dependent
      variations. With a standardized photographic set-up, systematic errors otherwise
      caused by variations in individual photographs of the same eye are insignificant.
      Use of this method may help in the achievement of more accurate testing for
      differences in secondary cataract formation with various types of IOL and
      different surgical techniques.

PMID- 8867159
TI  - [Outcome of corneal astigmatism after pars plana vitrectomy with or without
      simultaneous cataract extraction].
AB  - Changes in corneal astigmatism induced by pars plana vitrectomy (PPV) (group I,
      44 eyes) and PPV combined with no-stitch cataract surgery (group II, 20 eyes)
      were studied prospectively for a period of at least 3 months. The amount and
      orientation of the keratometric cylinder and the surgically induced astigmatism
      (according to the methods of Jaffe and Clayman or Naeser) were analysed. In the
      first postoperative week both groups exhibited a marked against-the-rule to
      oblique astigmatism (in group I up to 3.65 +/- 1.40 D, in group II up to 3.05 +/-
      1.60 D, according to Jaffe). After 3 months this had declined in group I to 0.40
      +/- 0.27 D, whereas a slight induced astigmatism (0.97 +/- 0.41 D) persisted in
      group II. Gas endotamponade did not significantly aggravate the postoperative
      astigmatism in either group. Computerized video-keratography generally revealed
      an asymmetric bowtie pattern during the first week. Our results show that PPV
      alone induces no appreciable long-term corneal astigmatism. Optical
      rehabilitation, however, can be delayed by a marked short-term postoperative
      astigmatism. PPV with simultaneous no-stitch cataract surgery, by contrast, was
      found to induce a persisting slight astigmatism against the rule.

PMID- 8867160
TI  - [Postoperative course of intraocular pressure after uncomplicated cataract
      operation with and without acetazolamide].
AB  - We prospectively analyzed the course of intraocular pressure (IOP) within the
      first 20 h after uncomplicated phacoemulsification with lens-implantation in the
      capsule sac with and without acetazolamide. Sixty patients were divided into two
      groups with 30 patients each, group 1 [mean age 72.3 years, (49-88 years);
      preoperative IOP 14.2 +/- 2.41 mmHg (10-18 mmHg)] did not receive systemic IOP
      lowering medication; group 2 [mean age 72.4 years, (53-88 years); preoperative
      IOP 14.7 +/- 2.98 mmHg, (9-20 mmHg)] received .250 mg acetazolamide intravenously
      immediately after surgery. The IOP was measured 6 and 20 h postoperatively with
      an applanation tonometer. In group 1 the IOP was 17.9 +/- 5.50 mmHg (7-28 mmHg)
      after 6 h, in group 2 16.6 +/- 5.51 mmHg (9-32 mmHg). In group 1, 8 patients
      (26.6%) had an IOP of more than 21 after 6 h and in group 2, 6 patients (20%).
      Statistically, there was no significant difference between groups after 6 h (P >
      0.05). After 20 h the IOP was 15.9 +/- 4.50 mmHg (7-28 mmHg) in group 1 and 13.5
      +/- 4.46 mmHg (7-26 mmHg) in group 2. Additionally, the two groups tended to be
      equal with 2 patients each with an IOP of more than 21 mmHg. After 20 h, there
      was a significant reduction in the IOP each group. Intravenous acetazolamide (250
      mg) did not have a clinical relevant influence on IOP after uncomplicated
      phacoemulsification.

PMID- 8867161
TI  - [Treatment with tissue plasminogen activator (tPA) in risk patients with fibrin
      reactions after cataract operations].
AB  - The postoperative course after cataract surgery can be complicated by the
      formation of severe fibrinous membranes, especially in cases with previous
      goniotrepanation, after syn echiolysis, iridotomy or iris suturing, and in
      patients with diabetes or uveitis. This study retrospectively analyzes the
      efficacy of intraocular tissue plasminogen activator (tPA) for fibrinolysis in
      these conditions commonly considered as contraindications to tPA therapy. When
      antiinflammatory therapy was unsuccessful in lysing fibrinous membranes, 10
      micrograms of tPA (Actilyse) was injected into the anterior chamber following the
      first postoperative day (n = 15). In addition, topical corticosteroids and
      cycloplegics were given postoperatively. Lysis of the fibrinous membranes was
      achieved in all patients. However, in three cases lysis was incomplete or
      recurred. Complications of intraocular tPA therapy consisted of mild hyphema (n =
      1) and transient dysfunction of the corneal endothelial cells (n = 2). In
      conclusion, the results suggest intraocular low-dose tPA as an effective approach
      for the treatment of severe fibrinous membranes after cataract surgery even in
      high-risk patients.

PMID- 8867162
TI  - [Regulation of glutathione level in venous plasma and aqueous humor in cataracta
      senilis provecta].
AB  - Glutathione is a major component of the mechanisms protecting the eye against
      oxidants. To analyse the functional status and the regulation of the glutathione
      system in the eyes of patients with advanced cataract, glutathione concentrations
      were quantified in venous plasma and aqueous humor. METHODS: In all, 42 patients
      with advanced cataract (29 women, 13 men; mean age (+/- SEM) 70 +/- 2 years;
      vision < or = 0.3) were evaluated. Aqueous humour and venous plasma were obtained
      at the beginning of cataract surgery. RESULTS: Levels of total glutathione
      [reduced (GSH) + oxidized glutathione (GSSG)] in plasma were 2.34 +/- 0.23
      microM. There was 2.08 +/- 0.15 microM in the reduced form and 0.27 +/- 0.17
      microM oxidized glutathione, which means that 94.7 +/- 2.1% of the total
      glutathione was GSH, the form fully functional as an antioxidant. Levels of total
      glutathione in the aqueous humor were 1.2 +/- 0.16 microM, i.e. 54.5 +/- 4.8% of
      plasma levels. Surprisingly, the percentage of GSSG in aqueous humor (0.24 +/-
      0.07 microM, 31 +/- 10.5% of the total glutathione) was much higher than that in
      plasma (P < 0.001). The correlation between glutathione concentrations in plasma
      and aqueous humor was on the borderline of significance (rs = 0.32, P < 0.04).
      CONCLUSION: The proportion of oxidized glutathione is higher in aqueous humor
      than in plasma of patients with advanced senile cataracts, indicating increased
      oxidant stress in the eye. Further, the regulation of the glutathione system in
      the eye, at least in aqueous humor, is dependent on plasma glutathione levels.
      This correlation reflects the importance of sufficient glutathione levels in
      venous plasma and suggests the possibility of modulating the glutathione system
      in the eye via manipulation of plasma glutathione levels.

PMID- 8867164
TI  - [Eyedrop anesthesia in cataract surgery].
AB  - Retro- und peribulbar anesthetic injections, the common techniques in cataract
      surgery, have persistently reported complications. Recently topical anesthesia
      has been mentioned as a possible alternative. The effectiveness of anesthesia,
      the acceptance on the part of the patients and the consequences of the lack of
      akinesia were analysed in a prospective study. We compared two groups of 27
      patients. Patients in the first group had only topical anesthesia, while patients
      in the control group had a peribulbar injection. None of the patients included
      had such conditions as deafness or dementia or felt overanxious. Both methods
      were accepted very well by the patients. There were no significant differences in
      the improvement of visual acuity and the opinion of the patients about pain
      during the operation. The surgeon's assessment revealed a few cases of increased
      voluntary eye movements in the topical anesthesia group, but this did not affect
      the complication rate significantly. There was one case of vitreous loss in each
      group and in the peribulbar group one case of zonular defect. Topical anesthesia
      should be seen as an alternative to injection anesthesia.

PMID- 8867163
TI  - [Perioperative follow-up of physiologic and cognitive functions after oral
      premedication with midazolam 3.75 mg in women for retrobulbar anesthesia].
AB  - Recent changes in the medical system have resulted in a significant increase in
      the number of surgical procedures performed as day surgery. Therefore, a safe and
      short postoperative recovery period has become increasingly important. In the
      present study we investigated perioperative cognitive and physiological functions
      after oral premedication with low-dose midazolam (3.75 mg). The study was carried
      out on at total of 55 women (age > 60 years, weight 50-90 kg) scheduled for
      elective cataract surgery under retrobulbar anaesthesia (RBA), who were randomly
      assigned to either group 1 (n = 35) receiving 3.75 mg midazolam p.o. or group 2
      (n = 20) receiving placebo p.o. 30 min prior to RBA. We measured the following
      parameters: sedation (modified Glasgow Coma Scale); anxiety (visual analogue
      scale); numerical and verbal memory (digit span and reproduction of previously
      presented words); concentration (revision test of Stender/Marschner). To identify
      depression of ventilation, pulse oximetric oxygenation and end-tidal PCO2 (nasal)
      were monitored intraoperatively. In the midazolam group anxiety was significantly
      lower and patients were significantly more sedated than in group 2. At a check 30
      min after premedication with midazolam the scores for concentration and numerical
      memory were significantly (P < 0.05) lower. No differences between the groups
      could be found 2 h after the operations (2.92 +/- 35 min after premedication).
      Intraoperatively there was no significant difference in end-tital PCO2 and
      oxygenation between the groups. Oral administration of low-dose midazolam (3.75
      mg) seems to be an appropriate form of premedication for ambulatory surgical
      procedures in elderly patients.

PMID- 8867165
TI  - [Experimental experiences with balloon-shaped capsular sac implantation with
      reference to accommodation outcome in intraocular lenses].
AB  - Implantation of a balloon into the capsular bag theoretically allows the
      injection of fluid materials for lens replacement, thus enabling accommodation.
      Leakage of the fluid can be avoided in this way, and a large variety of potential
      materials can be tested without taking into account their effect on ocular
      tissue. We tested ellipsoid balloons made of polydimethylsiloxane. The balloons
      had a maximum diameter of 11.0 mm and a wall thickness of 0.15 mm. After
      capsulorhexis of 2.5 mm and phacoemulsification, the balloons were implanted in
      enucleated pig eyes and filled with 2% methylcellulose or silicone oil through
      little tubes on the anterior side. Implantation of the balloons into the capsular
      sac was much more difficult than normal IOL implantation into the posterior
      chamber. We had to enlarge the tunnel incision to 4.5 mm, and it was technically
      difficult to leave the relatively strong capsule of the pig intact during
      implantation. Due to the additional surfaces we found increased reflection.
      Because of the difficulties described we cannot see any advantages over other
      refilling techniques.

PMID- 8867166
TI  - [Glaucoma and aircraft pilot fitness].
AB  - Two completely different questions arise when considering glaucoma and fitness to
      fly: Firstly, what is the risk for a passenger with glaucoma? Secondly, what is
      the flight safety risk connected with pilots suffering from glaucoma? National
      requirements and international standards pay little regard to this disease. This
      is astonishing, given that the perception of flight information in the peripheral
      visual field is of great importance in the cockpit. On one hand, diagnostic
      glaucoma examinations for pilots are mainly insufficient, and on the other,
      progressive visual field deficiencies may go undetected because of long intervals
      between examinations. Intraocular pressure may increase while flying in aircraft,
      e.g. in the case of negative g-load. Frequent flights at high altitudes without
      pressurized cabin air and with decreased oxygen supply, and therefore decreased
      tissue oxygen saturation, may represent a risk, especially for patients with
      progressive nerve fibre loss.

PMID- 8867167
TI  - [Local carbonic anhydrase inhibitor dorzolamide: development and properties].

PMID- 8867168
TI  - Mycobacterial infections in Finland.
AB  - In Finland, the situation with regard to tuberculosis has been constantly
      improving during recent years, and the WHO criteria for a low incidence country
      (10/100,000) are presently satisfied. In contrast, the number of clinical
      specimens yielding atypical mycobacteria by isolation has rapidly increased.
      Organisms belonging in Mycobaterium avium-intracellulare complex dominate among
      the isolated species.

PMID- 8867169
TI  - Isolation of potentially pathogenic mycobacteria in the Finnish environment.
AB  - Atypical mycobacteria have become more common in clinical samples, and their
      reservoirs, known to be in the environment, are poorly identified. In the Finnish
      natural environment, mycobacteria can be cultivated from surface waters in a mean
      of 1500 CFU/l and from soil samples in a mean of 3.6 x 10(5) CFU/g dry weight.
      The majority of isolates are not pathogenic to man. Less than 10% of cultivable
      mycobacteria belong in species which are also found in human samples, either as
      infectious agents or as harmless colonizers of human epithelia. The two most
      important potentially pathogenic atypical mycobacteria in Finland, the
      Mycobacterium avium-intracellulare-scrofulaceum (MAIS) complex and M. malmoense,
      were detected in 40% and 4%, respectively, of the examined waters.

PMID- 8867170
TI  - Mycobacterial infections in Norway.
AB  - Tuberculosis was a major health problem in Norway in the first part of the
      century, but since the thirties there has been a dramatic and steady decline in
      incidence. However, for various reasons, including tuberculosis in foreign-born
      residents, there has been no definite decrease in notified cases during the last
      decade. The emergence of drug resistant strains of M. tuberculosis has up to now
      not been a problem of any significance. Leprosy reached its peak incidence in the
      19th century. Nowadays the few imported cases seen, on average less than one a
      year, may represent a diagnostic challenge. Therapeutically, we have adopted a
      modification of the multidrug regime introduced and recommended by WHO a decade
      ago. Available figures indicate that diseases due to other mycobacteria, so
      called atypical mycobacteria, may be an increasing problem. A small part of the
      observed increase is due to infections with Mycobacterium avium-intracellulare
      complex in AIDS patients.

PMID- 8867171
TI  - Mycobacterial infections in Sweden.
AB  - The incidence of tuberculosis has continued to decline in the Swedish-born
      population, but there has been an increase in the foreign-born population,
      especially among young adults and children. Multidrug-resistant tuberculosis is
      still rare in Sweden. The annual number of patients with culture confirmed
      atypical mycobacteria, especially of M. avium-intracellulare, has increased. The
      increased incidence of atypical mycobacteria observed in non-BCG vaccinated
      Swedish children seems to be related to the restricted BCG policy brought into
      force in 1975.

PMID- 8867172
TI  - Drug-resistant mycobacterium tuberculosis; some data from Sweden, Estonia and
      Ethiopia.
AB  - Drug-resistant tuberculosis is a threat not only to the estimated 50 million
      people in the world carrying resistant strains, but also to the success of
      national TB control programmes. In Sweden, multidrug-resistant (MDR) tuberculosis
      comprises around 1% of the isolated strains. Isoniazid resistance is found in 7%
      of strains and resistance to other drugs in < 3%. Of patients with resistant TB
      70% are born outside Scandinavia. Preliminary data from Estonia show that close
      to 20% of the strains are resistant to each of the drugs isoniazid, rifampicin
      and streptomycin. MDR is seen in around 16%. In a study in Ethiopia isoniazid
      resistance was found in 46% and MDR in 11% among treatment failures and relapse
      cases.

PMID- 8867173
TI  - Clinical manifestations and treatment of mycobacterium avium-intracellulare
      complex infection in HIV-infected patients.
AB  - Disseminated infection caused by Mycobacterium avium-intracellulare complex is a
      common late opportunistic infection in HIV-infected patients. The clinical
      manifestations are non-specific, with fever, respiratory and gastrointestinal
      tract symptoms and weight loss. Blood culture is an easy and safe way of
      diagnosing the infection. Treatment can reduce symptoms and probably increase the
      quality of life and survival. An optimal treatment regimen is not established and
      has to be identified in comparative studies. According to the available data, the
      first line of drugs is ethambutol, clarithromycin or rifabutin and the second
      amikacin, clofazimin, azitromycin. Combination therapy must contain at least two
      or three drugs.

PMID- 8867174
TI  - Treatment of mycobacterial infections in HIV-negative immunocompromised patients.
AB  - Rifabutin is a useful drug in the treatment of patients with rifampicin-resistant
      mycobacteriosis or with rifampicin intolerance. Rifabutin is the preferable drug
      in patients infected with mycobacteria who concomitantly receive
      immunosuppressive drugs, because interactions with these are less prominent than
      with rifampicin.

PMID- 8867175
TI  - Clinical experience with rifabutin in the treatment of mycobacterial infections.
AB  - Effective new therapies are required to combat the increasing incidence of
      mycobacterial infections. Rifabutin has been investigated in studies conducted in
      various countries around the world, and in the treatment of tuberculosis
      rifabutin in combination regimen has been shown to be as effective as rifampicin.
      Rifabutin is active in approximately 30% of patients with tuberculosis resistant
      to standard therapies, including rifampicin and/or isoniazid. Placebo-controlled
      studies of rifabutin in the treatment of Mycobacterium avium-intracellulare
      complex (MAC) infection in AIDS patients have provided evidence for the inclusion
      of rifabutin in multidrug regimens. Rifabutin as a single agent is the only drug
      approved for the prophylaxis of MAC infection. Clinical experience indicates that
      rifabutin is well tolerated and that it does not reduce the tolerability of
      combination regimens.

PMID- 8867176
TI  - Mycobacterium paratuberculosis and Crohn's disease.
AB  - Mycobacterium paratuberculosis is the causative agent of Johne's disease, a
      chronic enteritis in ruminants. It has been suggested that Crohn's disease, a
      gastrointestinal disease in humans with similar clinical symptoms and
      histopathological findings, is caused by the same bacteria. Epidemiological data
      support Crohn's disease possibly being caused by an infectious agent. Recently,
      with improved culture techniques and the advent of polymerase chain reaction, M.
      paratuberculosis has been identified from tissues of increasing numbers of
      patients with Crohn's disease. However, conflicting data still occur and the case
      for M. paratuberculosis as the etiological agent of Crohn's disease can be
      neither proved nor disproved. The development of new diagnostic tests and
      comprehensive well-defined clinical studies will hopefully provide us with
      information about this association in the future.

PMID- 8867177
TI  - Improving influenza vaccine coverage. Where we are and where we should be
      heading.

PMID- 8867178
TI  - Options for electoral change.

PMID- 8867179
TI  - CME--what works?

PMID- 8867180
TI  - Management issues in herpes zoster.
AB  - Herpes zoster is a common clinical illness, with acute and chronic pain a major
      feature. Antiviral agents started within 72 hours of the onset of the rash are
      effective in the acute illness and in post herpetic neuralgia or zoster
      associated pain. Newer agents offer advantages in efficacy and dosage
      convenience.

PMID- 8867181
TI  - Options in asthma management.
AB  - This paper emphasises the strategies that can be used by general practitioners in
      the management of asthma and reviews the new medications available for the severe
      asthmatic population. The principles of asthma management involve the assessment
      of asthma severity and the assessment of risk factors. An effective review
      process entails: identification of immediate patient concerns; a review of
      symptoms; lung function; and detection of altered compliance. In the setting of
      poor compliance additional strategies can be applied. Three relatively new
      medications are available. Salmeterol (long acting beta 2 agonist) and
      fluticasone (inhaled corticosteroid) are for use in the small proportion of
      asthmatics who have severe asthma. Nedocromil sodium is a cromoglycate-like drug
      mainly suitable for treatment of milder asthmatics.

PMID- 8867182
TI  - New horizons in the treatment of psoriasis and cutaneous fungal infections.
AB  - This article takes a historical perspective and makes an assessment of current
      and future changes in the treatment of psoriasis and cutaneous fungal infections.
      Both medical and physical therapies in the management of psoriasis are reviewed
      and an assessment of the new approaches, compared with the old, is made. The
      vexing problem of cutaneous fungal infections is considered and the newer topical
      preparations are reviewed. With the arrival of these newer products improved
      outcomes for psoriasis and cutaneous fungal infections are being found.

PMID- 8867183
TI  - The acute phase response and laboratory testing.
AB  - Medical practitioners use laboratory testing to define disease states more
      precisely than is possible by clinical assessment alone. With this expectation it
      is easy to overemphasise the significance of numerical test results. There are
      many pitfalls in the interpretation of tests used to assess the body's general
      response to injury. This article reviews the nature of the response and
      highlights both the use of the available laboratory tests and some of the
      difficulties commonly encountered.

PMID- 8867184
TI  - Case studies in endocrine hypertension.
AB  - The diagnosis of various types of endocrine hypertension is discussed by way of
      illustrative cases. The emphasis of the article is on practical management. In
      particular, the clues that suggest a secondary form of hypertension are described
      along with the appropriate screening tests. The use of the aldosterone/renin
      ratio in diagnosis of primary aldosteronism represents a new concept which should
      increase the frequency of diagnosis of this condition. In addition, the diagnosis
      of pheochromocytoma is discussed by way of three cases where the diagnosis was
      made by appropriate follow-up of adrenal masses ('incidentalomas'), incidentally
      discovered on abdominal imaging. The diagnosis of endocrine hypertension remains,
      for the most part, a combination of good clinical judgement and a few well chosen
      laboratory tests.

PMID- 8867185
TI  - Innovative perspectives in youth health care.
AB  - A dedicated youth health service in an 'adolescent friendly' environment can
      provide a needed alternative to mainstream general practice for the large sub
      group of adolescents who require confidential management of their sexual health
      and psychological needs. Such a service has been operating in Melton, Victoria,
      since November 1993 under the name of the Backdoor Youth-Health Service.

PMID- 8867186
TI  - An adolescent hepatitis B immunisation program. The Preston experience.
AB  - An adolescent hepatitis B immunisation program was conducted in all post primary
      schools in the City of Preston, Melbourne, Victoria, in 1993. The program was
      funded entirely by the City of Preston using SmithKline Beecham, Engerix B Adult
      Vaccine. A total of 857 Year 9 students in 8 schools were offered a three-dose
      course of Hepatitis B vaccine; 85% of all students elected to enter the program;
      78% of all students completed the program; 95% of students who started the
      program completed the three-dose schedule. No side effects from the 2041 doses
      were reported. The program was well accepted and tolerated by the students with
      minimum side effects at a total cost of $34 per completed course.

PMID- 8867187
TI  - Immunisation in general practice. Results from the Australian Morbidity and
      Treatment Survey, 1990-1991.
AB  - Immunisation is the sixth most commonly managed problem in general practice in
      Australia. This paper provides an overview of its management in general practice.

PMID- 8867188
TI  - Options in education for advanced trainees in isolated general practice.
AB  - BACKGROUND: Only a small number of remote solo doctors are needed each year to
      provide health care to remote communities. However, despite advances in the
      provision of appropriate training for intending rural doctors, the preparation of
      graduates for this kind of medical practice has received little attention.
      OBJECTIVE: To develop and evaluate an optional training unit within the Royal
      Australian College of General Practitioners Training Program, which provides
      trainee GPs with an opportunity to learn about remote medicine during training
      with the distant support of an experienced rural doctor. METHOD: A program of
      intensive educational support was developed and piloted with a group of nine GP
      in solo rural practices and compared to that provided to four GP trainees in
      standard advanced GP terms. Comparison was based on data collected in trainee
      logbooks and in questionnaires completed by trainees and supervisors. RESULTS:
      The solo trainees received equivalent duration of educational support through the
      use of communications technology and other distance education methods. The
      training unit will be trialed further and may remain an option within the
      Training Program.

PMID- 8867189
TI  - Patients, carers and the medical profession: a co-operative approach.
AB  - This article is reprinted (with minor editing) from the Queensland Council of
      Carers newsletter for members. The Council's Public Policy Forum, held in
      September 1994, raised problems faced by carers, some of which related to the
      relationship between patients, carers, and the medical profession. Their concerns
      were circulated to the Divisions of General Practice, who in turn delegated the
      author to contact the Queensland Council of Carers, with a view to improving co
      operation and clarifying mutual expectations.

PMID- 8867190
TI  - General practice audit as a quality assurance activity. An evaluation of the
      Morbidity and Therapeutic Index.
AB  - Quality assurance is a topical issue in general practice. This study examined the
      Morbidity and Therapeutic Index (MTI), a self-audit activity, offered as a QA
      option by the RACGP. GP response to this activity was generally positive and it
      appears to be an adequate tool for performance review. The study highlights the
      problems of assessing the extent to which the MTI leads to change and improvement
      in quality of care.

PMID- 8867191
TI  - Becoming a GP facilitator. A training approach.
AB  - The UNSW School of Medical Education has devised a training program for general
      practitioners to develop skills as GP facilitators involved with small groups in
      Continuing Medical Education programs and was offered in 1994. This program was
      well received by the participants and further developments are under way. Prior
      research on the most effective CME strategies for general practitioners confirms
      the value of this approach.

PMID- 8867192
TI  - Kaposi's sarcoma.

PMID- 8867193
TI  - Difficulties in diagnosing ectopic pregnancy with pelvic ultrasound.

PMID- 8867194
TI  - Why do some doctors become addicted?

PMID- 8867195
TI  - Suicide and overdose among opiate addicts.

PMID- 8867196
TI  - Public health consequences of the J-curve hypothesis of alcohol problems.
AB  - This paper addresses some issues related to the hypothesis that the risk for
      premature death is a J-shaped function of alcohol intake. The first part of the
      paper contains a discussion of the individual level epidemiological evidence. It
      is argued that the evidence is not yet good enough to allow precise statements
      about "safe limits", nor does it allow a precise location of the "optimum"
      consumption level. Measurement errors and confounding variables not yet
      controlled for remain substantial problems. In particular, future studies need to
      control for social integration, as this factor may affect both health status and
      alcohol consumption. The second part of the paper discusses the population level
      relationship. It is argued that, typically, what is optimum for an individual is
      too much for a population. Unintended side effects of major public health
      importance should be expected in this area. In the last section, a plea is made
      for aggregate level studies as a way of addressing the public health side of the
      issue.

PMID- 8867197
TI  - Per capita alcohol consumption and total mortality: an analysis of historical
      data.
AB  - Since total mortality is a classical proxy for the overall health status of the
      population, its degree of association with per capita alcohol consumption is of
      great interest. Existing evidence, based on historical data from the turn of the
      century, is mostly in graphical form. These data are analysed using modern
      statistical tools. The results suggest a significant alcohol effect; a 1-l
      increase in consumption is expected to increase mortality (middle-aged men) by
      about 1%. This effect might seem fairly modest but it is noted that it may well
      be locally substantial because of its concentration to specific categories of the
      population. The alcohol effect is also compared with the impact of a factor that
      is a surrogate for a large number of etiological agents, namely real wages.
      Although the latter factor seems to be the more important one the difference is
      not overwhelming. The shift in the cause of the death panorama during this
      century, with an increasing share of CHD-mortality, may well have attenuated the
      aggregate relationship between alcohol and mortality.

PMID- 8867198
TI  - Moderating drinking by correspondence: an evaluation of a new method of
      intervention.
AB  - Recognizing the need to offer alternative methods of brief interventions, this
      study developed correspondence treatments for low-dependent problem drinkers and
      evaluated their impact. One hundred and twenty-one problem drinkers were
      recruited by media advertisements and were randomly allocated to a full cognitive
      behavioural treatment programme (CBT) or to a minimal intervention condition (MI)
      that gave information regarding alcohol misuse and instructions to record
      drinking++. As predicted, CBT was more effective than MI in reducing alcohol
      consumption over the 4-month controlled trial period. CBT produced a 50% fall in
      consumption, bringing the average intake of subjects within recommended maximum
      levels. Treatment gains at 6 months were well maintained to 12 months. High
      levels of consumer satisfaction, a high representation of women and a substantial
      participation from isolated rural areas attested to the feasibility of the
      correspondence programme as an alternative treatment. However, some drinking
      occasions still involved high intake for a significant subgroup of subjects, and
      this issue will be addressed in future programmes. The results supported the use
      of correspondence delivery as a means of promoting early engagement and equity of
      access between city and country areas.

PMID- 8867199
TI  - Gender differences in drinking behaviour in the Netherlands: convergence or
      stability?
AB  - Gender differences in drinking behavior are analysed with emphasis on their
      relationship with changes in roles and positions of men and women in society. The
      'convergence hypothesis' is used as a starting point. From its implications, a
      number of specific hypotheses are derived and tested using data from six surveys
      of the general population of the Netherlands, held between 1958 and 1993. No
      convergence of gender differences is found for abstinence and heavy frequent
      drinking. Convergence of male-female differences in average weekly consumption
      appeared in the 1980s, but it is no longer significant at 5% level after
      controlling for age, education and family situation. Further elaboration of the
      gender by year interaction shows that convergence is related to a decrease in
      consumption among higher educated men. Contrary to expectation, an increase in
      consumption has occurred among women over 40 years of age. No relationship
      appears with female employment and religion. Having a family is related to lower
      consumption among women, while it has no significant effect on men's consumption.
      Although some evidence for convergence was found, results are not in agreement
      with expectations formulated from the perspective of the convergence hypothesis.

PMID- 8867200
TI  - Alcohol consumption in high school adolescents: frequency of use and dimensional
      structure of associated problems.
AB  - The goal of this paper is to present data regarding the occurrence of alcohol
      consumption and the relative prevalences and the factorial structure of DSM-IV
      symptoms of alcohol abuse/dependence in a sample of 1507 older (14-18 years)
      community adolescents. Participants were diagnostically assessed at two time
      points, approximately 1 year apart. Three-quarters of the sample had tried
      alcohol. Boys in general had greater usual frequency and quantity of alcohol
      consumption than girls and began drinking at an earlier age; girls with a
      diagnosis of alcohol abuse/dependence had a significantly earlier mean age of
      alcohol disorder onset and were more likely to have a relapse of alcohol
      disorder. However, gender differences in symptom prevalence were non-significant.
      Seventeen per cent of the sample had at least one alcohol abuse/dependence
      symptom. The most frequent symptoms included reduced activities because of
      alcohol use, consumed more than intended, and tolerance. Eight of the 11 symptoms
      made a unique contribution to the prediction of diagnosis in a multiple logistic
      regression analysis. Components analysis supported the general division of
      symptoms into the categories of abuse and dependence.

PMID- 8867201
TI  - Perceived workplace harassment experiences and problem drinking among physicians:
      broadening the stress/alienation paradigm.
AB  - Sociologists who embrace the stress or alienation paradigms generally focus on
      explaining problem drinking in low status occupations. By contrast, this paper
      argues that a broadened conceptualization of stress and alienation which
      incorporates abusive work relationships has utility for explaining male and
      female drinking outcomes in both high and low status occupations. We provide
      empirical data on the relationship between perceived abusive experiences and
      drinking outcomes in a cohort of male and female physicians in their internship
      year of training. The data show that perceived sexual harassment, discriminatory
      treatment and psychological humiliation relate to various drinking outcomes in
      men and women, controlling for drinking prior to the internship year. While
      females were more likely to report experiencing abuse, these perceived
      experiences had deleterious effects on drinking outcomes for both genders.
      Personal vulnerability (narcissism) brought into the training environment
      somewhat influenced the later reporting of abusive experiences by males but not
      by females. Regression analyses showed that, for both males and females, work
      place abusive experiences in interaction with personality vulnerability best
      explained drinking outcomes. The implications of these results for the design of
      future alcohol-related work-place studies are discussed.

PMID- 8867202
TI  - Overdose among heroin users in Sydney, Australia: I. Prevalence and correlates of
      non-fatal overdose.
AB  - A sample of 329 heroin users were interviewed regarding their personal experience
      of non-fatal heroin overdose. Experience of overdose was widespread, with two
      thirds of subjects (68%) reporting having overdosed. The median number of life
      time overdoses was three, with males and females equally likely to have
      overdosed. The majority (62%) of most recent heroin overdoses occurred in
      conjunction with the consumption of other central nervous system depressants
      (alcohol, benzodiazepines and other opioids). Logistic regression analyses
      indicated three independent factors associated with having overdosed: longer
      heroin using careers, greater heroin dependence and higher levels of alcohol
      consumption. Implications for the reduction in the prevalence and frequency of
      overdose are discussed.

PMID- 8867203
TI  - Overdose among heroin users in Sydney, Australia: II. responses to overdose.
AB  - A sample of 329 heroin users were interviewed about their experiences at other
      peoples' heroin overdoses. The overwhelming majority (86%) had witnessed a heroin
      overdose, on a median of six occasions. Heroin users were reluctant to seek
      medical attention, with an ambulance being called on only half (56%) of the most
      recent overdose occasions. At only 17% of most recent overdoses was calling an
      ambulance the first action taken. Males reported taking significantly longer than
      females to call an ambulance. Nearly half (44%) of subjects reported that there
      were factors that had delayed or stopped them seeking medical assistance, the
      most common impediment being a fear of police involvement. The importance of
      interventions to encourage help-seeking at overdoses are discussed.

PMID- 8867204
TI  - Mortality due to acute adverse drug reactions: opiates and cocaine in Barcelona,
      1989-93.
AB  - Drug-related deaths have become a major source of premature mortality. This paper
      presents an analysis of deaths due to acute adverse drug reactions caused by
      opiates or cocaine in the city of Barcelona over a 5-year period during which
      figures were stable. Annual mortality rates due to adverse drug reactions of city
      residents for the 1989-93 period were estimated to be 15.3 per 100,000 people in
      the 15-49-year age group. Mortality rates for men (25.0) are consistently higher
      than mortality rates for women (5.8). Mortality rates by age group show different
      patterns by gender. Males in the 25-29-year group have the highest mortality rate
      (62.8), almost doubling the rates for the 20-24 (36.1) and 30-34 (33.3)-year
      groups. The highest differential in age-specific mortality by gender is seen in
      the 35-39-year age group, where mortality rates for men (21.5) are eight times
      higher than for women (2.6 per 100,000). The distribution by place of residence,
      stratifying data across city neighbourhoods and municipal districts displays wide
      differences between districts in the mean annual rates, ranking between 77.3 and
      8.3 per 100,000, a nine-fold magnitude. Differences are even steeper when we
      break down data by neighbourhood. Although all areas with high adverse drug
      reactions mortality are areas of low socio-economic level, a more complex
      association between deprivation and drug use must exist, as other areas with
      similarly low socio-economic indicators do not suffer from such high mortality. A
      cross-tabulation of place of residence and district of death shows that for most
      adverse drug reaction deaths, death takes place in the district of residence but
      patterns related to districts who attract drug-related deaths and districts who
      export them may be observed. These results provide new insights into the
      epidemiology of substance abuse in Barcelona, where it follows patterns that may
      be similar to those of other major urban areas in Spain, but also in other
      Southern European countries.

PMID- 8867205
TI  - The association between having children, family size and smoking cessation in
      adults.
AB  - This study aimed to examine the relationship between rates of smoking cessation
      in adults and whether or not they have dependent children at home. Previous work
      has suggested that among women, particularly poor women, caring for young
      children might work against giving up smoking, while the relationship between
      having children and giving up smoking in men is largely unexplored. The analysis
      employed data from 3 years (1988, 1990 and 1992) of the General Household Survey,
      and assessed rates of self-reported smoking cessation among adult ever-smokers of
      cigarettes aged 16-49 years. After adjustment for a wide range of potential
      confounding variables, adults with dependent children were more likely to have
      given up smoking than those without. Among women there was a linear increase in
      the odds of cessation with each additional child. Using the combined data from
      the 3 years, and by comparison with those with no children, the adjusted odds of
      cessation were 1.42 (95% CI 1.21-1.67) in women with one dependent child, 1.77
      (1.50-2.09) in those with two and 2.19 (1.74-2.74) in those with three or more.
      The effect was marginally present in men, with an increase in the odds of
      cessation of about 25% in those with two or more dependent children. (Estimated
      odds from the combined data 1.30 (1.09-1.50) for men with two dependent children
      and 1.23 (0.97-1.51) for those with three or more.) The association of increased
      rates of smoking cessation with number of dependent children did not vary with
      level of deprivation. It is concluded that having children is associated with
      smoking cessation in parents, whether poor or affluent. Health education
      campaigns targeted at families with children could aim to amplify this effect.

PMID- 8867206
TI  - HIV infection in females dependent on drugs.
AB  - One hundred and seventy-one drug-dependent females in a drug rehabilitation
      centre were studied to estimate the prevalence of HIV infection among them.
      Twenty-four (14%) were positive on the Western Blot test. The presence of HIV
      infection was significantly correlated with syphilis (p < 0.03) and age (p <
      0.001); 83% of those who were HIV positive were intravenous drug users. The need
      for harm reduction programmes to prevent spread of HIV infection among injecting
      drug users is stressed.

PMID- 8867207
TI  - The impact of a bistrand abasic lesion on DNA duplex properties.

PMID- 8867208
TI  - The statistics of unique native states for random peptides.
AB  - Given a probability distribution from which the energy spectrum of a random
      peptide is to be sampled, we derive a general expression for the probability that
      such a peptide will fold to a unique native state and for the probability
      distribution of the native energy. This latter result allows us to localize the
      energy of folding based on model parameters and is one advantage of our
      formulation. Evidence from both the lattice theory of proteins and protein
      threading experiments suggest that the energy spectrum for the compact states of
      a peptide chain is Gaussian in form. For this reason we have derived from the
      more general framework the specific formulas that apply in the Gaussian case,
      where one requires only the number of states and the variance of the Gaussian
      distribution in order to apply the theory. This simplicity allows us to perform
      calculations that we compare with calculations previously made by others based on
      statistical thermodynamics. We find qualitative agreement, but a significant
      correction to prior estimates of folding probability derived from the Gaussian
      assumption is necessary.

PMID- 8867209
TI  - The effect of hydration upon the conformation and dynamics of neocarrabiose, a
      repeat unit of beta-carrageenan.
AB  - Molecular mechanics calculations have been performed for the disaccharide
      neocarrabiose, one of the repeat units of beta-carrageenan, as a general model
      for the (1-->3)-linkage in the carrageenans. An adiabatic conformational energy
      map for this molecule has been prepared by constrained energy minimization and
      compared to previously reported relaxed maps. Neither the experimentally
      determined crystal structure of neocarrabiose nor the fiber diffraction
      conformation of iota-carrageenan is a low energy conformation on the relaxed
      Ramachandran map. Molecular dynamics simulations in vacuum produced trajectories
      consistent with this relaxed vacuum surface. However, a simulation with
      explicitly included solvent water molecules produced a trajectory that remained
      in the region of the two experimental structures. This dramatic solvation effect
      is apparently the result of the breaking of an interring hydrogen bond between
      the O2 hydroxyl groups of neocarrabiose as both groups hydrogen bond to solvent.

PMID- 8867210
TI  - Isolation, characterization, and magnesium-induced self-association kinetics of
      discrete aggregates of RecA protein from Escherichia coli.
AB  - Dynamic and static intensity light scattering techniques were employed to
      identify conditions allowing preparation of homogeneous solutions of distinct
      oligomeric states of RecA protein. These hydrodynamically distinguishable
      oligomer populations of RecA protein were obtained in homogeneous pure quantities
      sufficient for physical studies. Results indicate two fairly narrow distributions
      of RecA oligomers comprised on average of 42 +/- 3 and 18 +/- 1 RecA monomers.
      These structures, denoted RecA42 and RecA18, respectively, could be obtained
      reproducibly in milligram quantities and were stable for at least one week. This
      enabled reliable characterizations of their hydrodynamic properties by dynamic
      and total intensity light scattering. These measurements revealed RecA42 had an
      average translational diffusion coefficient, D20(L) = 8 +/- 2 x 10(-8) cm2/s,
      molecular weight, M(r) = 1.6 +/- 0.1 x 10(6), and radius of gyration, RG = 465 +/
      29 A. The smaller aggregate, RecA18, had D20(S) = 20.5 +/- 2.5 x 10(-8) cm2/s,
      M(r) = 7.0 +/- 0.4 x 10(5), and RG = 300 +/- 20 A. Heating RecA18 at 37 degrees C
      overnight resulted in conversion to a species with hydrodynamic properties
      indistinguishable from RecA42, called RecA18/42. Conversion of RecA42 to RecA18
      occurred almost instantaneously by 50% dilution at 38 degrees C or very slowly
      with incubation at 4 degrees C for at least 39 days. Self-association reactions
      of the three starting oligomeric states (RecA18, RecA42, and RecA18/42) induced
      by MgCl2 were monitored at several temperatures by dynamic light scattering.
      Results of these experiments provided evaluations of kinetic activation
      parameters of the self-association reactions. The activation parameters found for
      each starting oligomeric state of the protein were significantly different,
      revealing the variable influence of MgCl2 on the activation barriers to RecA self
      association. Highly aggregated equilibrium solutions that ultimately form in
      solutions of each starting oligomeric species, incubated in MgCl2 at 38 degrees C
      for four days, were characterized by total intensity light scattering.
      Interpretations of these data in terms of characteristic behavior of random
      polymers suggests the surface morphologies of these highly associated equilibrium
      states formed from RecA42 and RecA18/42 are similar but contrast with that of
      RecA18. Calculated values of the translational diffusion coefficient D0 were
      obtained for oligomeric structures modeled as helical arrays of connected monomer
      spheres. Best agreement with experimentally determined diffusion coefficients
      required that constituent monomer spheres of RecA42 have radii 33-40% larger than
      the monomer spheres of RecA18. Results suggest the hydrodynamically distinct
      oligomeric forms of RecA may reside in conformational states with different
      surface exposure of hydrophobic residues, which results in substantial
      differences in local solvation/hydration.

PMID- 8867211
TI  - Thermodynamics of the first transition in writhe of a small circular DNA by Monte
      Carlo simulation.
AB  - Monte Carlo simulations are employed to investigate the thermodynamics of the
      first transition in writhe of a circular model filament corresponding to a 468
      base-pair DNA. Parameters employed in these simulations are the torsional
      rigidity, C = 2.0 x 10(-19) dyne cm2, and persistence length, P = 500 A.
      Intersubunit interactions are modeled by a screened Coulomb potential. For a
      straight line of subunits this accurately approximates the nonlinear Poisson
      Boltzmann potential of a cylinder with the linear charge density of DNA. Curves
      of relative free energy vs writhe at fixed linking difference (delta l) exhibit
      two minima, one corresponding to slightly writhed circles and one to slightly
      underwrithed figure-8's, whenever delta l lies in the transition region. The free
      energies of the two minima are equal when delta lc = 1.35, which defines the
      midpoint of the transition. At this midpoint, the free energy barrier between the
      two minima is found to be delta Gbar = (0.20) kBT at 298 K. Curves of mean
      potential energy vs writhe at fixed linking difference similarly exhibit two
      minima for delta l values in the transition region, and the two minimum mean
      potential energies are equal when delta l = 1.50. At the midpoint writhe, delta
      lc = 1.35, the difference in mean potential energy between the minimum free
      energy figure-8 and circle states is (1.3) kBT, and the difference in their
      entropies is 1.3 kB. Thus, the entropy of the minimum free energy figure-8 state
      significantly exceeds that of the circle at the midpoint of the transition. The
      first transition in writhe is found to occur over a rather broad range of delta l
      values from 0.85 to 1.85. The twist energy parameter (ET), which governs the
      overall free energy of supercoiling, undergoes a sigmoidal decrease, while the
      translational diffusion coefficient undergoes a sigmoidal increase, over this
      same range. The static structure factor exhibits an increase, which reflects a
      decrease in radius of gyration associated with the circle to figure-8 transition.

PMID- 8867212
TI  - An NMR self-diffusion study of the interactions between spermidine and
      oligonucleotides.
AB  - Self-diffusion coefficients have been determined by pulsed field gradient nmr
      methods for spermidine in solutions of the oligonucleotides d(GC)4 and
      d(GGAATTCC). The self-diffusion behavior of spermidine in solution of d(GC)4 is
      very similar to that observed previously for methylspermidine (completely N
      methylated spermidine). Moreover, the self-diffusion behaviors of spermidine in
      solutions of d(GC)4 and d(GGAATTCC) are also quite similar, indicating that there
      is no significant influenceon on self-diffusion of oligonucleotide base
      composition. Furthermore, self-diffusion coefficients of the oligonucleotide
      d(GC)8 show only a small dependence on oligonucleotide concentration, and no
      measurable dependence on sodium ion or magnesium ion concentration.

PMID- 8867213
TI  - Solid state and solution conformations of a helical peptide with a central Gly
      Gly segment.
AB  - The influence of amino acids with contrasting conformational tendencies on the
      stereochemistry of oligopeptides has been investigated using an octapeptide Boc
      Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe, which contains two helix-promoting Aib
      residues and a central helix-destabilizing Gly-Gly segment. Single crystal x-ray
      diffraction studies reveal that a 3(10)-helix is formed up to the penultimate Aib
      residue, at which point there is a helix reversal in the backbone, reminiscent of
      a C-terminal 6-->1 hydrogen bond. The curious feature in the crystal is the
      solvation of the possible 6-->1 bond by a CH3OH molecule, where the OH is
      inserted between O(3) and N(8) and participates in hydrogen bonds with both. The
      cell parameters are as follows: space group P2(1)2(1)2(1), a = 10.649 (4) A, b =
      15.694 (5) A, c = 30.181 (8) A, R = 6.7% for 3427 data (magnitude of F0 > 3 sigma
      F) observed to 0.9 A. Nuclear magnetic resonance studies in CDCl3 using NH group
      solvent accessibility and nuclear Overhauser effects as probes are consistent
      with a 3(10)-helical conformation. In contrast, in (CD3)2SO, unfolding of the
      central segment results in a multiple beta-turn structure, with beta-turn
      conformations populated at residues 1-2, 3-4, and 6-7. CD studies in methanol
      2,2,2-trifluoroethanol (TFE) mixtures also provide evidence for a solvent
      dependent structural transition. Helical conformations are populated in TFE,
      while type II beta-turn structures are favored in methanol.

PMID- 8867214
TI  - Light scattering studies of supercoiled and nicked DNA.
AB  - Static and dynamic light scattering measurements were made of solutions of pGem1a
      plasmids (3730 base pairs) in the relaxed circular (nicked) and supercoiled
      forms. The static structure factor and the spectrum of decay modes in the
      autocorrelation function were examined in order to determine the salient
      differences between the behaviors of nicked DNA and supercoiled DNA. The
      concentrations studied are within the dilute regime, which is to say that the
      structure and dynamics of an isolated DNA molecule were probed. Static light
      scattering measurements yielded estimates for the molecular weight M, second
      virial coefficient A2, and radius of gyration RG. For the nicked DNA, M = (2.8 +/
      0.4) x 10(6) g/mol, A2 = (0.9 +/- 0.2) x 10(-3) mol cm3/g2, and RG = 90 +/- 3 nm
      were obtained. For the supercoiled DNA, M = (2.5 +/- 0.4) x 10(6) g/mol, A2 =
      (1.2 +/- 0.2) x 10(-3) mol cm3/g2, and RG = 82 +/- 2.5 nm were obtained. The
      static structure factors for the nicked and supercoiled DNA were found to
      superpose when they were scaled by the radius of gyration. The intrinsic
      stiffness of DNA was evident in the static light scattering data. Homodyne
      intensity autocorrelation functions were collected for both DNAs at several
      angles, or scattering vectors. At the smallest scattering vectors the probe size
      was comparable to the longest intramolecular distance, while at the largest
      scattering vectors the probe size was smaller than the persistence length of the
      DNA. Values of the self-diffusion coefficients D were obtained from the low-angle
      data. For the DNA, D = (2.9 +/- 0.3) x 10(-8) cm2/s, and for the supercoiled DNA,
      D = (4.11 +/- 0.21) x 10(-8) cm2/s. The contribution to the correlation function
      from the internal dynamics of the DNA was seen to result in a strictly bimodal
      decay function. The rates of the faster mode gamma int, reached plateau values at
      low angles. For the nicked DNA, gamma int = 2500 +/- 500 s-1, and for the
      supercoiled DNA, gamma int = 5000 +/- 500 s-1. These rates correspond to the
      slowest internal relaxation modes of the DNAs. The dependence of the relaxation
      rates on scattering vector was monitored with the aid of cumulants analysis and
      compared with theoretical predictions for the semiflexible ring molecule. The
      internal mode rates and the dependence of the cumulants moments reflected the
      difference between the nicked DNA and the supercoiled DNA dynamical behavior. The
      supercoiled DNA behavior seen here indicates that conformational dynamics might
      play a larger role in DNA behavior than is suggested by the notion of a branched
      interwound structure.

PMID- 8867215
TI  - Assignment of the disulfide bonds in the sweet protein brazzein.
AB  - The thermostable sweet protein brazzein consists of 54 amino acid residues and
      has four intramolecular disulfide bonds, the location of which is unknown. We
      found that brazzein resists enzymatic hydrolysis at enzyme/substrate ratios (w/w)
      of 1:100-1:10 at 35-40 degrees C for 24-48 h. Brazzein was hydrolyzed using
      thermolysin at an enzyme/substrate ratio of 1:1 (w/w) in water, pH 5.5, for 6 h
      and at 50 degrees C. The disulfide bonds were determined, by a combination of
      mass spectrometric analysis and amino acid sequencing of cystine-containing
      peptides, to be between Cys4-Cys52, Cys16-Cys37, Cys22-Cys47, and Cys26-Cys49.
      These disulfide bonds contribute to its thermostability.

PMID- 8867216
TI  - A world of opportunities.

PMID- 8867217
TI  - The Spanish version of the Parental Stressor Scale: Pediatric Intensive Care
      Unit.
AB  - The Spanish Parental Stressor Scale: Pediatric Intensive Care Unit (SPSS:PICU)
      was developed to assess Hispanic parents' perceptions of stressful stimuli in the
      PICU. Twenty parents completed a personal data sheet and the SPSS:PICU. Alpha
      coefficients were 0.91 for the total scale and ranged from 0.47 to 0.94 for the
      subscales. The Sights and Sounds and Procedures subscales were the most stressful
      to Hispanic parents. Significant positive correlations were found between
      SPSS:PICU scores and parents' level of education. Although further instrument
      validation is suggested, this pilot study of the SPSS:PICU instrument proved to
      be reliable in assessing Hispanic parents' perceptions of stress.

PMID- 8867218
TI  - The use of projective techniques in pediatric nursing research from 1984 to 1993.
AB  - The purpose of this study was to review and analyze the use of projective
      techniques in published nursing studies in which children were the subjects. A
      search of the pediatric nursing research literature revealed 27 studies that were
      published between 1984 and 1993 in which projective techniques were used to
      investigate children's responses. The research purposes, characteristics of
      subjects, projective techniques employed and their validity and reliability, data
      analysis strategies, and major findings of the studies reviewed are analyzed and
      summarized. Recommendations for the use of projective techniques in research and
      clinical practice with children are offered.

PMID- 8867219
TI  - A clinical tool for nonorganic failure-to-thrive feeding interactions.
AB  - An interdisciplinary team of professionals developed and piloted a clinical tool,
      the Feeding Checklist, for assisting observations of feeding interactions with
      nonorganic failure-to-thrive (NOFTT) clients. The piloting process involved two
      phases. During the development phase, content validity and reliability were
      established with three NOFTT experts. The tool was compared with a standardized
      feeding interaction assessment instrument to determine concurrent validity. Both
      tools revealed similar behavior patterns significantly differentiating between
      NOFTT and Thriving dyads. The results also concurred with NOFTT literature
      findings. During the second phase of the study, pediatric nursing staff
      significantly improved the nursing documentation of NOFTT feeding interactions
      when using the Feeding Checklist.

PMID- 8867220
TI  - Cholesterol levels in children: to screen or not to screen.
AB  - Universal screening and targeted screening are the two approaches used in
      pediatric practice to identify children with elevated cholesterol levels. This
      study reports total cholesterol levels in 415 2-year-old children and the
      relationship of these results to risk factors. Based on these data, universal
      screening for total cholesterol (TC) does not appear to be necessary. Targeted
      screening for TC may be the more practical method for identifying children with
      dangerously high TC elevations.

PMID- 8867221
TI  - Deaf and hearing mothers' interactions with normally hearing infants and
      toddlers.
AB  - The purpose of this study was to compare the interactions between Deaf mothers
      and their normally hearing infants and toddlers with the interactions between
      hearing mothers and their normally hearing infants and toddlers. The Nursing
      Child Assessment Teaching Scale (NCATS), modified to credit Deaf mothers and
      their children for both spoken and signed communications, was used to assess
      mother-child interactions. There were no statistically significant differences in
      scores on the NCATS Parent subscales, NCATS Child subscales, or in total NCATS
      scores of the Deaf mother/child dyads compared with the hearing mother/child
      dyads. Implications for clinical practice are discussed.

PMID- 8867222
TI  - A child with chronic illness and the process of family adaptation.
AB  - This article analyzes the concept of family adaptation to a child with chronic
      illness according to the Wilson method. This concept is viewed developmentally as
      a continual process of adjustment and change by a family system with a resultant
      response found across a continuum from optimal to ineffective adaptation. In a
      developmental context, the family system is viewed from a health-oriented rather
      than a pathological perspective. The focus is on the family's ability to address
      the stressful chronic illness situation rather than centering on maladaptation of
      the family and subsequent treatment.

PMID- 8867223
TI  - Health and welfare reform, part 1: the origins.

PMID- 8867224
TI  - Toward one standard of care: sedation of pediatric patients.

PMID- 8867225
TI  - "They feel your needs in the air": experiences of supportive activities among
      adolescents with ulcerative colitis.

PMID- 8867226
TI  - Independent plenary prescriptive authority.

PMID- 8867227
TI  - Thyroglossal duct cyst mass with Hashimoto's disease and non-Hodgkin's lymphoma.

PMID- 8867228
TI  - Pulmonary abscess due to Corynebacterium striatum.
AB  - Non-diphtheria corynebacteria are normal commensals of the skin and mucous
      membranes of humans. Increasingly, however, these saprophytic organisms are being
      recognized as pathogens. Patients infected with these bacteria typically have an
      underlying immunosuppressive process and/or an indwelling venous catheter.
      Pleuropulmonary infection with Corynebacterium striatum is rare. We present a
      patient with diabetes mellitus who developed an intrapulmonary abscess due to C.
      striatum.

PMID- 8867229
TI  - Diaphragmatic rupture.

PMID- 8867230
TI  - Bilateral adrenal hemorrhage and acute addisonian crisis--a complication of
      antiphospholipid syndrome.

PMID- 8867231
TI  - A case of penicillin-resistant pneumococcal meningitis.

PMID- 8867232
TI  - Prevention in managed care: obstacles and opportunities.
AB  - Managed care will present many new challenges to health care providers in their
      efforts to improve the quality of the preventive care their patients receive.
      Managed care will present both formidable obstacles to prevention and previously
      unknown opportunities to enhance population-based preventive services. Whether
      these opportunities are realized depends on the degree and quality of the
      involvement of health care providers in managed care institutions. Provider and
      public health input is particularly needed to promote the development of uniform
      preventive care standards, the development of information systems for continuous
      monitoring of preventive service delivery, and to enhance clinic-based preventive
      efforts, and the development of reimbursement mechanisms that provide incentives
      for prevention. Independent research and oversight is needed to show the impact
      of various types of managed care on preventive service delivery and quality of
      care. The effects of managed care on the preventive care that patients receive
      will ultimately be determined by the quality, priorities, and determination of
      the management.

PMID- 8867233
TI  - Breastfeeding promotion--a community consortium approach.

PMID- 8867234
TI  - Outcomes can be very unexpected.

PMID- 8867235
TI  - Flotsam and Jetsam.

PMID- 8867236
TI  - Antiretroviral therapy 1996.

PMID- 8867237
TI  - Introduction of newborn screening for galactosemia to Arkansas.

PMID- 8867238
TI  - Physician-to-physician communication.

PMID- 8867239
TI  - Dicrotism: examples and review of the dicrotic pulse.

PMID- 8867240
TI  - A review of Vibrio vulnificus infections related to eating raw oysters, including
      three cases in Arkansas residents.

PMID- 8867241
TI  - Radiological case of the month.

PMID- 8867242
TI  - Post-sympathectomy neuralgia: hypotheses on peripheral and central neuronal
      mechanisms.
AB  - Post-sympathectomy neuralgia is proposed here to be a complex neuropathic and
      central deafferentation/reafferentation syndrome dependent on: (a) the
      transection, during sympathectomy, of paraspinal somatic and visceral afferent
      axons within the sympathetic trunk; (b) the subsequent cell death of many of the
      axotomized afferent neurons, resulting in central deafferentation; and (c) the
      persistent sensitization of spinal nociceptive neurons by painful conditions
      present prior to sympathectomy. Viscerosomatic convergence, collateral sprouting
      of afferents, and mechanisms associated with sympathetically maintained pain are
      all proposed to be important to the development of the syndrome.

PMID- 8867243
TI  - Medial frontal cortex lesions selectively attenuate the hot plate response:
      possible nocifensive apraxia in the rat.
AB  - Lesions in the cingulate cortex have attenuated pain-related behavior in humans.
      We wished to evaluate an animal model of this effect by studying the effects of
      bilateral lesions within the medial frontal cortex, including rat cingulate
      cortex, on performance in 3 behavioral tests: the formalin, hot-plate, and tail
      flick tests. Average hot-plate latencies, but not formalin test scores or tail
      flick latencies, were significantly increased by an average of 82% in rats with
      medial frontal cortex lesions, as compared to sham-operated control rats. Motor
      function, as tested by righting and foot lifting responses and clinical
      observation, was not impaired. No effects were seen on hot-plate latencies, tail
      flick latencies, and formalin pain scores in sham-operated rats. These results
      suggest that the medial frontal cortex of the rat mediates certain types of
      supraspinally organized responses to noxious heat pain. Lesions that include the
      medial frontal and anterior cingulate cortex appear to disrupt the integration of
      increasing heat nociceptive input with motor responses that are necessary to
      execute quickly the escape behavior in the hot-plate test.

PMID- 8867244
TI  - The formalin test in rat: validation of an automated system.
AB  - A novel, computer-driven, dynamic-force detector was validated for use in
      measuring the formalin-induced agitation response. Intraplantar administration of
      formalin (0.25-5%) provoked a biphasic agitation response as measured with the
      automated system. The magnitude of both phases of the response increased with the
      intensity of the noxious stimulus. Morphine (1-5 mg/kg, s.c.) inhibited both
      phase 1 and 2 of the agitation response evoked by 5% formalin with ID50 values of
      2.07 +/- 0.47 and 1.35 +/- 0.02 mg/kg, respectively. The non-peptide, NK1
      antagonist, (+/-)-CP-96,345 (30 mg/kg, s.c.), partially blocked phase 2 but did
      not alter the magnitude of phase 1. These results are comparable with those
      obtained by us and others using a multiple-pain-behavior scoring system or
      certain uni-dimensional measures. In addition, they indicate that the automated
      system yields a valid measure of the formalin-induced agitation response.

PMID- 8867245
TI  - Contributions of injured and intact afferents to neuropathic pain in an
      experimental rat model.
AB  - This study was conducted to determine the contribution of peripheral inputs from
      injured and intact afferent fibers to behavioral signs of neuropathic pain, using
      a previously developed neuropathic rat model. Neuropathic injury was produced by
      tightly ligating the left L5 and L6 spinal nerves; this procedure induced rats to
      display neuropathic pain behaviors in the ipsilateral hindlimb. The behaviors
      included signs of mechanical and cold allodynia, as well as ongoing pain. Five
      days after neuropathic injury, peripheral inputs from injured segments (L5 and
      L6) or intact segments (L3 and L4) were blocked by either transection of the
      dorsal roots or application of a local anesthetic (bupivacaine) to the roots.
      Dorsal rhizotomy of the injured segments reduced all components of neuropathic
      pain behaviors. In contrast, dorsal rhizotomy of the uninjured segments abolished
      behavioral signs of mechanical and cold allodynia, but signs of ongoing pain were
      preserved. Blocking afferent inputs by application of bupivacaine mimicked the
      results of dorsal rhizotomy, in a reversible manner. These results suggest that
      afferent signals from injured and intact fibers play distinctively different
      roles in neuropathic pain: inputs from injured afferents maintain all components
      of neuropathic pain, while those from intact afferents mediate evoked pain such
      as mechanical and cold allodynia. An hypothesis is proposed to explain the
      results of the present as well as other published studies.

PMID- 8867246
TI  - Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a
      painful neuropathy: ultrastructural morphometric analysis of axonal alterations.
AB  - Polyethylene cuffs of varying inner diameters were applied to the rat sciatic or
      sural nerve with the aim of inducing a standardized nerve injury, as assessed by
      morphometric analyses of fiber-size spectrum alterations, associated with
      behavioral manifestations of neuropathic pain. The temporal sequence of axonal
      degeneration and regeneration was examined in parallel with behavioral analyses
      of pain initiation and recovery over a 6-week postoperative (PO) period. Cuffs of
      0.028-0.030" inner diameter loosely enclosed sciatic nerves of young rats and
      elicited relatively uniform axonal degeneration and 'pain'. Large myelinated
      axons underwent an early and sustained numerical depletion. Both the thinly
      myelinated and unmyelinated axon populations were initially diminished, but later
      rose to levels significantly greater than control values, likely the result of:
      (1) demyelination, (2) early stages of remyelination, (3) regenerative sprouting,
      and/or (4) collateral sprouting of undamaged unmyelinated axons. Pathological
      alterations of the injured nerve included edematous swelling, hypertrophy of the
      perineurial sheath, infiltration of fibroblasts and collagen into the
      intraneurial compartment, increasing interaxonal space and decreasing order and
      density of axonal packing. Animals displayed maximal pain-related behaviors,
      including gait and postural asymmetries and hypersensitivity to mechanical
      compression and cold, during the 2nd week PO and had largely recovered by
      approximately 4 weeks PO. Consistent behavioral manifestations of pain were
      achieved over a wide range of fiber spectrum alteration; however, with the
      largest cuffs or 'bracelets' used in this study, a substantial axonal fiber
      spectrum change was produced without inducing pain-related behavior, suggesting
      that decrement in the number of myelinated axons was not always sufficient to
      elicit pain. Similar morphometric and pathological results were achieved with
      sural neuropathy after 0.010" ID cuffs and 14 days PO survival. Considering the
      lack of correlation between axonal alterations and pain, modification in the
      local intraneurial microenvironment at the site of injury may be a key component
      of peripheral pain mechanisms; these include changes in the biochemical milieu,
      increased intraneurial pressure, and altered nociceptor sensitivity or impulse
      propagation in the relatively intact unmyelinated axon population.

PMID- 8867247
TI  - Lignocaine selectively reduces C fibre-evoked neuronal activity in rat spinal
      cord in vitro by decreasing N-methyl-D-aspartate and neurokinin receptor-mediated
      post-synaptic depolarizations; implications for the development of novel
      centrally acting analgesics.
AB  - The action of lignocaine on nociceptive transmission in the spinal cord has been
      studied in vitro using ventral root potential (VRP) recordings from 10-12-day-old
      rat hemisected spinal cord preparations. Single-shock stimulation of a dorsal
      root at intensities sufficient to activate high-threshold C-primary afferent
      fibres elicited VRPs lasting for 15-20 sec in the corresponding ventral root. The
      VRP consisted of 3 distinct parts: the early, slow and prolonged components, as
      previously described (Thompson et al. 1992), where the early represents A beta
      fibre-evoked mono- and polysynaptic responses lasting for tens of milliseconds,
      the slow is a largely N-methyl-D-aspartic acid (NMDA) receptor-mediated small
      calibre afferent-generated component, lasting for about 1.5 sec, and the
      prolonged is a neurokinin receptor-mediated long-lasting component generated by
      high-threshold fibres. Lignocaine superfusion (40-60 microM) significantly and
      reversibly reduced the slow and prolonged components of the C fibre-evoked VRP in
      a dose-dependent manner without any effect on the early or A beta fibre-mediated
      component of the VRP. The amplitude of the cumulative VRP generated by repetitive
      inputs (1 and 10 Hz) was also significantly reduced as was the depolarization
      produced by bath application of NMDA (100 microM) or substance P (SP, 1 microM)
      in the presence or absence of tetrodotoxin (TTX) (300 nM). At this dose range
      lignocaine had no effect on the compound action potential (CAP) elicited by
      stimulating the sciatic nerve and recorded on the dorsal root. The CAP was only
      significantly reduced with a 300 microM dose of lignocaine. Application of the
      opiate, glycine, GABAA and GABAB receptor antagonists, naloxone (1 microM),
      strychnine (100 microM), bicuculline (100 microM) and phaclofen (100 microM) did
      not alter the depressant effects of lignocaine on the VRP. Low concentrations of
      lignocaine have a selective action on nociceptive transmission in the spinal cord
      which is different and more potent than its local anaesthetic conduction blockade
      in the periphery. This includes a reduction of direct or synaptically driven NMDA
      and NK receptor-mediated post-synaptic depolarizations indicating that this
      class of sodium channel blockers may be potentially useful as analgesic agents,
      possibly acting on TTX-resistant sodium ion channels.

PMID- 8867248
TI  - Dose-dependent competitive block by topical acetylsalicylic and salicylic acid of
      low pH-induced cutaneous pain.
AB  - In a human acid pain model, which uses continuous intradermal pressure infusion
      of a phosphate-buffered solution (pH 5.2) to induce localized non-adapting pain,
      the flow was adjusted to result in constant pain ratings of about 20% or 50% on a
      visual analog scale (VAS). Six volunteers in each group participated in 4
      different placebo-controlled double-blind cross-over studies to measure rapidly
      evolving cutaneous analgesia from topically applied new ointment formulations of
      acetylsalicylic acid (ASA) and salicylic acid (SA) as well as of commercial
      ibuprofen and benzocain creams. Similar, log-linear dose-response curves were
      found for both ASA and SA, significant in effect at 3 g/kg and higher drug
      contents and reaching saturation level at 15 or 30 g/kg, respectively, which, 20
      min after application, caused a mean pain suppression of 95% using ASA and 80%
      using SA. Half-maximal effects were achieved using 3 g/kg ASA or 15 g/kg SA. The
      SA action was also clearly slower to develop. With an increased flow of the
      acidic buffer, producing lower effective tissue pH and more intense pain, the
      effect of ASA and SA decreased to 73% pain suppression. A competitive mechanism
      of both drug effects was suggested by the fact that, with 15 g/kg ASA and SA,
      pain reduction could be reversed by increasing the buffer flow by a factor of
      1.75, on average. Commercial ibuprofen (50 g/kg) and benzocain creams (100 g/kg)
      were comparably as effective as ASA and SA, but the local anesthetic caused a
      loss of all cutaneous sensations while the touch threshold (von Frey) under the
      specific analgesics was the same as under the placebo ointment. Thus, topical
      applications of non-steroidal anti-inflammatory drugs (NSAIDS) dissolved in
      different ointment formulations have proven dose-dependently effective and
      specific in suppressing experimental acidotic pain by a local and competitive
      mechanism.

PMID- 8867249
TI  - Parents' management of children's pain following 'minor' surgery.
AB  - The aim of the investigation was to evaluate the prevalence, severity, and
      parents' management of children's pain following short-stay and day surgery. The
      subjects were 189 parents of children (2-12 years of age) who had undergone short
      stay or day surgery. Parents completed a 3-day diary of their child's pain and
      the methods used to alleviate it. There were clear differences in pain reported
      according to type of surgery. Some surgery, such as insertion of myringotomy
      tubes, appeared to cause little pain. Other procedures, including tonsillectomy,
      circumcision, and strabismus repair, resulted in about one-half the children
      experiencing clinically significant pain (> or = 30 mm on a 100 mm VAS). Sixty
      eight percent of the parents reported they had been instructed to use
      acetaminophen for pain 'if necessary', 13% had been told to use acetaminophen
      regularly, and 8% recalled no instructions. Of the parents who rated their
      child's pain as significant, 13% administered no pain medication and 47% gave 1-3
      doses on day 2. On day 3, 17% gave no medication and 45% gave 1-3 doses. Some
      types of 'minor' surgery result in significant pain postoperatively. Even when
      parents recognise that their children are in pain, most give inadequate doses of
      medication to control the pain.

PMID- 8867250
TI  - Determinants of success and failure of EMLA.
AB  - Although EMLA is known to be an effective topical anesthetic, its rate of success
      is unknown. Indeed, researchers have suggested that EMLA may fail with young and
      apprehensive children. Therefore, the objectives of this study were to assess
      EMLA's rate of success as well as factors which predict success. A double-blind,
      placebo-controlled design was utilized. The sample included 258 children and
      adolescents aged 5-18 years who were having venipuncture or intravenous (i.v.)
      cannulation. After having their anxiety assessed, subjects were randomly assigned
      to have EMLA or placebo applied over the procedure site for 90 min. The visual
      analogue scale was used to assess pain caused by removal of the semi-permeable
      dressing and by the procedure. Other information that was collected included:
      duration of drug application, interval between drug removal and procedure, skin
      changes at bandage and drug sites and rated difficulty of the procedure. EMLA was
      successful 84% of the time for venipuncture and 51% of the time for i.v.
      cannulation. Factors which predicted success of EMLA included type of procedure,
      duration of drug application and anxiety. EMLA was less successful for i.v.
      cannulation compared to venipuncture even with duration of drug application
      controlled. Those who had a poor outcome were more anxious than those with a good
      outcome. Age of child was not a factor. Strategies for improving efficient use of
      EMLA were recommended.

PMID- 8867251
TI  - Ro 15-8081 in osteoarthritis of hip and knee: a double-blind placebo-controlled
      multicentre dose-ranging study on analgesia.
AB  - Ro 15-8081, a substituted cyclohexanol hydrochloride, inhibits the re-uptake of
      norepinephrine and of serotonin. Its antinociceptive properties have been
      demonstrated in animals and then confirmed in humans after single-dose
      administration. The objective was to determine the analgesic efficacy and the
      safety of Ro 15-8081 in osteoarthritis of the hip and knee (femoro-tibial
      location) after multiple-dose application. The design for studying dosage
      employed 5 parallel groups in an international multicenter, double-blind,
      randomized trial having a duration of 2 weeks. Drugs studied were: 20 mg Ro 15
      8081 (divided into 2 doses), 50 mg Ro 15-8081 (divided into 2 doses), 100 mg Ro
      15-8081 (divided into 2 doses), placebo twice daily or 20 mg/day piroxicam
      (piroxicam in the morning and placebo in the evening). Piroxicam was used as a
      reference drug in order to validate clinical testing. Assessment criteria were
      pain (100-mm VAS) and function (Lequesne's index). A responder (main assessment
      criterion) was defined as a patient exhibiting a reduction of at least 30% of
      pain (VAS) during the study (intention-to-treat analysis). A total of 522
      patients were enrolled in the study. A clear beneficial effect of piroxicam was
      observed when compared with placebo (70% and 48% of responders in piroxicam and
      placebo groups respectively; P < 0.0001). Multigroup comparison showed a
      statistically significant difference between Ro 15-8081 groups and the placebo
      group regarding mean change in pain between D1 and Dend and the rate of VAS
      responders. Comparison (Dunnett's t or chi 2 tests) between each individual Ro 15
      8081 and the placebo group reached statistical significance for the 100 mg Ro 15
      8081 group (mean change in pain between D1 and Dend: P = 0.05; percentage of
      responders: P = 0.0008) but no statistically significant difference for the other
      dosages of Ro 15-8081. Fifty-three patients withdrew from the study because of
      adverse events and/or inefficacy, mainly in 50 and 100 mg Ro 15-8081 groups and
      in a dose-related manner. The adverse events which appeared to be drug related
      were mainly dryness of the mouth, insomnia, headache, constipation, nausea,
      dizziness, nervousness, palpitation. This study suggests that 100 mg Ro 15-8081
      per day divided into 2 doses has (1) an analgesic effect in hip or knee
      osteoarthritis and (2) poor acceptability in the conditions of the study regimen
      application.

PMID- 8867252
TI  - Assessment of cancer pain: a prospective evaluation in 2266 cancer patients
      referred to a pain service.
AB  - Although pain assessment is a vital preliminary step towards the satisfactory
      control of cancer pain, data on the prevalence of different pain syndromes are
      rare. In a prospective study of 2266 cancer patients, we assessed localisations,
      aetiologies and pathophysiological mechanisms of the pain syndromes. Thirty
      percent of the patients presented with 1, 39% with 2 and 31% with 3 or more
      distinct pain syndromes. The majority of patients had pain caused by cancer (85%)
      or antineoplastic treatment (17%); 9% had pain related to cancer disease and 9%
      due to aetiologies unrelated to cancer. Pain could be classified as originating
      from nociceptors in bone (35%), soft tissue (45%) or visceral structures (33%) or
      otherwise as of an neuropathic origin (34%). In most patients, pain syndromes
      were located in the lower back (36%), abdominal region (27%), thoracic region
      (23%), lower limbs (21%), head (17%) and pelvic region (15%). The main pain
      syndrome was also coded according to the IASP Classification of Chronic Pain.
      Regions and systems affected by the main pain syndrome showed large variation
      depending on the site of cancer origin, whereas temporal characteristics,
      intensity and aetiology were not markedly influenced by the cancer site. The
      variety of pain syndromes evaluated in our patients confirms the importance of
      comprehensive pain assessment prior to treatment.

PMID- 8867253
TI  - A comparison of morphine, pethidine and fentanyl in the postsurgical patient
      controlled analgesia environment.
AB  - This study was designed to evaluate whether there is any scientific basis for
      clinicians' preferences for selecting opioids for use in patient-controlled
      analgesia (PCA) and to determine whether there are any patients' preferences for
      being treated with any of these opioids. Results were obtained for 55
      postoperative patients recruited to investigate putatively equivalent doses of 3
      commonly used opioids--morphine, pethidine and fentanyl--when self-administered
      postoperatively. No significant differences in the incidence of side effects
      between groups were found with the exception of more pruritus reported in the
      group given morphine. Patients who experienced vomiting or pruritus reported a
      greater intensity of these side effects if receiving morphine and fentanyl than
      if receiving pethidine. The majority of patients reported being very satisfied
      with their postoperative pain management and with PCA, with no differences in
      satisfaction between the 3 opioid-treated groups. A senior consultant
      anaesthetist, when asked to make a judgement, was not able to identify which
      agent each patient was receiving with a better than chance accuracy. These
      findings suggest that while there may be subtle differences in patient response
      to these 3 commonly used opioids, none was obviously superior when used for
      postoperative PCA.

PMID- 8867254
TI  - Experimental pain stimulates respiration and attenuates morphine-induced
      respiratory depression: a controlled study in human volunteers.
AB  - Although evidence is lacking, clinical experience suggests that pain stimulation
      acts as a respiratory stimulant and antagonises opioid-induced respiratory
      depression. The present study examined the effects of experimental pain
      stimulation on the ventilatory response to CO2 and morphine-induced respiratory
      depression. Pain was induced by a modification of the Tourniquet Pain Technique
      and changes in ventilatory parameters were registered through monitoring of the
      CO2 response of tidal volume, minute ventilation, respiratory rate and mouth
      occlusion pressure. The ventilatory parameters were obtained before and during
      pain stimulation and repeated after the administration of morphine and finally
      after naloxone. In the present investigation experimental pain-stimulated
      respiration and attenuated morphine-induced respiratory depression. Only changes
      in the intercept values of the CO2 response were observed. The slopes of the CO2
      response curves were not affected. These observations suggested that both pain
      stimulation and morphine administration altered the threshold of the respiratory
      centre to CO2 stimulation. Naloxone administration was the only intervention
      altering the sensitivity of the respiratory centre to CO2. These results suggest
      that pain stimulates respiration and attenuates morphine-induced respiratory
      depression.

PMID- 8867255
TI  - A comparison of the effects of noxious and innocuous counterstimuli on
      experimentally induced itch and pain.
AB  - We have studied experimentally induced itch (using histamine iontophoresis) and
      pain (using topical mustard oil) in healthy human volunteers, measured using
      visual analogue scale (VAS) ratings. The effects of the following counterstimuli
      were evaluated: innocuous vibration; innocuous transcutaneous electrical nerve
      stimulation (TENS); innocuous warming of skin; noxious heating of skin; noxious
      chemical skin stimulation (using mustard oil); mildly noxious constant current
      transdermal electrical stimulation. Innocuous stimuli applied 2 min after
      histamine or mustard oil challenge produced a modest reduction of itch and pain
      ratings (20-30%), which did not persist for more than 20 sec when the
      counterstimuli were removed. These changes may well be due to distraction. The
      same stimuli (in some cases applied for periods of up to 1 h) given prior to the
      histamine or mustard oil, produced no significant reduction in evoked itch or
      pain. Noxious stimuli of all types applied 2 min after histamine or mustard oil
      challenge produced a consistent and significant inhibition of itch (22.8-52.7%)
      which outlasted the period of counterstimulation application. In contrast, these
      stimuli had no significant effects on chemically induced pain. The anti-pruritic
      state produced by brief noxious stimuli were effective for periods of more than
      30 min. The differential effects of noxious counterstimuli on itch and pain do
      not support the suggestion that itch is a subliminal form of pain. Noxious
      counterstimuli are likely to act via a central rather than peripheral mechanism.
      The novel finding that a persistent anti-pruritic state can be induced by
      transdermal constant current may be useful in conditions of clinical itch.

PMID- 8867256
TI  - Nitric oxide as a chemical link in the generation of pain from veins in humans.
AB  - In humans, both nitric oxide (NO) and bradykinin, a naturally occurring algetic
      and a potent NO liberator, evoke pain from hand veins. The afferent innervation
      of these veins consists solely of polymodal nociceptors which are located close
      to the endothelium, a well-known source of NO, thus suggesting NO as a chemical
      link in nociception. Consistent with this hypothesis, our observations show that
      neither bradykinin, nor hyperosmolar solutions (a noxious physicochemical
      stimulus) evoke pain from hand vein segments that have been exposed to the NO
      synthase (NOS) inhibitor NG-mono-methyl-L-arginine. An intact NOS pathway is
      therefore a prerequisite for pain to be evoked by bradykinin and hyperosmolar
      solutions from veins, indicating for the first time in humans that vascular pain
      is mediated by NO. Thus, new directions for research on analgesics may be opened.

PMID- 8867257
TI  - The effect of age on A delta- and C-fibre thermal pain perception.
AB  - It has been suggested that ageing may have a differential effect on C fibre
      mediated protopathic/tonic pain versus epicritic/phasic pain perception mediated
      by A delta fibres. The present study attempted to independently assess age
      related changes in the function of A delta- and C-nociceptive fibres by examining
      CO2 laser-induced thermal pain thresholds before, during and after a compression
      block of the superficial radial nerve in 15 young and 15 healthy elderly adult
      subjects. Nerve block efficacy was monitored via measures of cold, warm and
      mechanical threshold, and simple reaction time. During nerve compression block,
      reaction time and mechanical threshold increased, cold sensation became impaired
      while warm sensation remained unaffected throughout the test in both groups. With
      respect to pain sensitivity, young adults exhibited significant increases in
      thermal pain threshold during A-fibre block while pain threshold remained
      relatively stable across the 3 test periods in the elderly group. It would appear
      that elderly adults rely predominantly on C-fibre input when reporting pain
      whereas younger adults utilise additional input from A delta fibres. Subsequent
      analysis revealed that during pre- and post-block periods, older adults exhibited
      a significant elevation in thermal pain threshold; however, when A delta-fibre
      function was impaired and only C-fibre information was available, both groups
      responded similarly. These findings support the notion of a differential age
      related change in A-fibre-mediated epicritic pain perception versus C-fibre
      mediated protopathic pain.

PMID- 8867258
TI  - Perception of fault in patients with chronic pain.
AB  - The beliefs and expectancies of chronic pain patients have been shown to be
      critical cognitive facilitators or impediments to the recovery process. In the
      present study patients presenting to an outpatient pain center were classified
      according to their response to the questionnaire item "Who do you think is at
      fault for your pain?". Patients were then grouped according to the responses
      'employer', 'other', or 'no one'. The resulting 3 groups of patients did not
      differ in current pain intensity or activity limitation, but the fault
      conditions, relative to the no-fault patients, reported greater concurrent mood
      distress and behavioral disturbance, as well as poorer response to past
      treatments, and lessor expectations of future benefits. The negative effects were
      more pronounced in the Employer-Fault group, than for the Other-Fault group
      (primarily 'doctors' and 'other drivers'). On balance, the present data suggest
      that attribution of blame may be an under-recognized cognitive correlate of pain
      behavior, mood disturbance, and poor response to treatment.

PMID- 8867259
TI  - The role of spinal cord activation before neurectomy in the development of
      autotomy.
AB  - A model of deafferentation pain is provided by sectioning the sciatic and
      saphenous nerves in the rat and mouse. This procedure leads to self-mutilation of
      the denervated hindpaw (autotomy). A noxious stimulus to the denervated area
      before neurectomy is known to enhance the autotomy. To understand the mechanism
      underlying this enhancement by prior noxious stimuli, we examined the effects of
      intrathecal (i.t.) injection of substance P (SP) and somatostatin (SOM) on
      autotomy behavior. These peptides are known to be released from primary afferent
      terminals in the dorsal horn by noxious stimuli. A single i.t. injection of SP or
      SOM just before neurectomy dramatically enhanced autotomy behavior in mice.
      Autotomy was enhanced in a dose-dependent manner with i.t. injection of SP (0.1
      20 nmol) 5 min before neurectomy or SOM (0.1-1.0 nmol) 20 min before neurectomy.
      Autotomy significantly decreased by extending the interval between i.t. injection
      of SP or SOM and neurectomy. Intact mice injected with the same doses of SP or
      SOM showed dose-dependent acute nociceptive responses directed to the hindpaw.
      The severity of autotomy in neurectomized mice and the duration of acute
      nociceptive responses induced by the same doses of SP or SOM in intact mice were
      related. These results suggest that neuropeptides applied to the spinal dorsal
      horn just before deafferentation induce a state of central neural activation with
      long-lasting effects on the function of CNS cells. Augmentation of autotomy is a
      result of this activation which is kept as a 'memory'.

PMID- 8867260
TI  - Estrogen and progesterone activate spinal kappa-opiate receptor analgesic
      mechanisms.
AB  - Rats and humans manifest elevated response thresholds to aversive stimuli during
      gestation and parturition. This pregnancy-associated antinociception is mediated,
      in part, by a spinal cord dynorphin/kappa antinociceptive system. Simulating the
      maternal pregnancy blood concentration profile (in non-pregnant animals) of 17
      beta-estradiol (E2) and progesterone (P) produces an opioid antinociception which
      closely approximates that of actual pregnancy. The current study was initiated in
      order to determine whether sex steroid-induced antinociception involves a spinal
      cord kappa-opiate receptor-coupled system (as does the antinociception of actual
      gestation). Additionally, sex steroid modulation of the intrathecal (i.t.)
      antinociceptive effectiveness of a kappa agonist was investigated. The opioid
      antinociception associated with simulating the pregnancy blood concentration
      profile of E2 and P (hormone-stimulated pregnancy, HSP) is significantly
      antagonized by i.t. administration of nor-binaltorphimine, an antagonist highly
      specific for the kappa-opiate receptor. This indicates that exposure (of non
      pregnant animals) to the pregnancy blood profile of E2 and P activates a spinal
      cord kappa-opiate receptor analgesic system, as occurs during actual gestation.
      Furthermore, during HSP, antinociceptive responsiveness to i.t. U50,488H (kappa
      selective) is significantly enhanced (approximately 40%). This effect is
      abolished in animals treated concomitantly with steroid hormones and systemic
      naltrexone or i.t. nor-binaltorphimine. In contrast to the effects of steroid
      treatment on antinociceptive responsiveness to i.t. U50,488H, no alteration in
      antinociceptive responsiveness to i.t. sufentanil was observed on day 19 of HSP
      over all doses tested (0.1-1 nmol). Thus, during HSP (and actual gestation), a
      less robust constituent of intrinsic opioid pain-attenuating systems in the
      spinal cord is recruited. pF to mediate, at least in part, the maternal
      antinociception of gestation. pF, positive modulation of the spinal cord kappa
      analgesic system occurs post-synaptically. This laboratory previously reported
      that simulating the pregnancy blood concentration profile of E2 and P also
      positively modulates spinal dynorphin content and the processing of its
      precursor, suggesting a presynaptic loci of action. Thus, female rats possess a
      spinal dynorphin/kappa analgesic system that can be positively modulated, pre
      synaptically as well as post-synaptically, by circulating sex steroids.

PMID- 8867261
TI  - The NMDA receptor antagonist MK-801 reduces Fos-like immunoreactivity in central
      trigeminal neurons and blocks select endocrine and autonomic responses to corneal
      stimulation in the rat.
AB  - The N-methyl-D-aspartate (NMDA) receptor is implicated in multiple aspects of
      pain processing by the central nervous system. However, the role of NMDA
      receptors in the endocrine and autonomic aspects of nociception remains
      uncertain. The present study examined the influence of the NMDA receptor
      antagonist, MK-801 (0.02-2.0 mg/kg, intracarotid), on the adrenal and autonomic
      responses to corneal stimulation (mustard oil, 20% sol.) in barbiturate
      anesthetized rats. Fos-like immunoreactivity (Fos-LI) evoked by corneal
      stimulation was quantified within the spinal trigeminal nucleus (Vsp) of MK-801
      pretreated animals to assess activation of central trigeminal neurons. Corneal
      stimulation-evoked increases in the plasma concentrations of adrenocorticotropin
      (ACTH), epinephrine and norepinephrine were reduced dose-dependently by MK-801.
      Plasma ACTH also increased after moderate hemorrhage, a response that was not
      affected by MK-801. MK-801 did not reduce the magnitude of corneal stimulation
      evoked increases in arterial pressure and heart rate; however, prestimulus
      arterial pressure was reduced by drug treatment. Fos-LI was distributed bimodally
      within the ipsilateral caudal Vsp: one peak of Fos-LI in the subnucleus
      interpolaris/caudalis transition region and a second peak within the superficial
      laminae of the subnucleus caudalis/upper cervical cord transition region. The
      magnitude of both peaks of Fos-LI was reduced dose-dependently by MK-801. These
      results indicate a significant contribution from NMDA receptors in control of
      select endocrine and autonomic responses that accompany trigeminal nociception
      and in activation of central trigeminal neurons that process corneal nociceptive
      input.

PMID- 8867262
TI  - Capsaicin activated currents in rat dorsal root ganglion cells.
AB  - Capsaicin is a pungent-tasting compound produced by plants in the Capsium family
      that activates a subset of primary afferent neurons associated with pain and
      thermoreception. Previous studies from dorsal root ganglion (DRGs) neurons
      suggest that many of capsaicin's physiological responses are a consequence of its
      activating a cation-selective current. To further characterize the responses to
      capsaicin whole-cell patch-clamp measurements were performed on rat DRGs to which
      0.1-10 microM capsaicin was continuously applied. The capsaicin-activated
      currents exhibited marked variability in their thresholds, amplitude (to 15 nA),
      rates of desensitization, and the number of distinct maxima in the evoked
      current. Similar responses were found in rat trigeminal ganglion cells. The
      heterogeneity in the magnitude of the currents evoked by 0.1 microM capsaicin
      likely reflects different types of capsaicin-sensitive neurons; a result
      consistent with in vitro extracellular recordings from capsaicin-sensitive
      sensory afferents (Seno and Dray 1993).

PMID- 8867263
TI  - Monitoring adequacy of alpha-adrenoceptor blockade following systemic
      phentolamine administration.
AB  - Systemic phentolamine administration has been suggested as a diagnostic tool for
      identifying patients with sympathetically maintained pain (SMP) (Raja et al.
      1991). The dose of phentolamine to produce adequate blockade of peripheral alpha
      adrenoceptor function has, however, not been previously determined. In this
      study, the effects of two different doses of phentolamine on peripheral
      sympathetic vasoconstrictor function were investigated. One-hundred and seventeen
      (117) patients with chronic extremity pain underwent 130 phentolamine diagnostic
      tests using two different doses of phentolamine (0.5 mg/kg over 20 min (n = 60)
      and 1 mg/kg over 10 min (n = 59)). Eleven (11) patients did not receive
      phentolamine during the test. Cutaneous temperature was measured in the distal
      extremity before and after administration of phentolamine. In a subset of
      patients, baseline blood flow and sympathetically mediated vasoconstrictor
      response (SMR) to deep inhalation were measured on glabrous skin using laser
      Doppler flowmetry. SMR was elicited with a 5-sec maximal inspiratory gasp. A dose
      related increase in cutaneous temperature was observed. In addition, baseline
      blood flow increased and SMR was attenuated after both doses of phentolamine, but
      to a greater degree after the 1 mg/kg dose. However, SMR was not completely
      attenuated, even after administration of the higher phentolamine dose. These
      results indicate that a phentolamine dose of 1 mg/kg over 10 min more completely
      blocks alpha-adrenoceptor function than a dose of 0.5 mg/kg over 20 min. We
      therefore recommend that to ensure adequate alpha-adrenoceptor blockade the
      higher phentolamine dose be used in the phentolamine diagnostic test for SMP.

PMID- 8867264
TI  - Additional comments on non-steroidal anti-inflammatory drugs and topical
      analgesia (PAIN, 61 (1995) 494-495).

PMID- 8867265
TI  - Pain specialists and pain terms.

PMID- 8867266
TI  - Comments on Pilowskey et al.

PMID- 8867267
TI  - Does invasive medical treatment confound the assessment of out-patient cognitive
      behavioral therapy for chronic non-malignant pain?

PMID- 8867268
TI  - Claims for lost chance of survival in Missouri.

PMID- 8867269
TI  - The changing face of Medicare peer review: collaborative project success stories.

PMID- 8867270
TI  - Preparing a per-member-per-month capitated bid to a managed care plan.

PMID- 8867271
TI  - Attention deficit hyperactivity disorder, infantile autism, and elevated blood
      lead: a possible relationship.
AB  - This case involves a 4 1/2-year-old boy diagnosed with autism, attention deficit
      hyperactivity disorder (ADHD), and an elevated blood-lead level of 42 mcg/dl. The
      child was treated for the elevated blood-lead with the chelating agent succimer.
      The parents reported a decrease in repetitive behaviors while on succimer with a
      regression to previous symptoms when medication was discontinued. Also seen was a
      decrease of hyperactive behavior while being treated with succimer. This article
      explores the interaction and possible casual relationship of an elevated blood
      lead, autism, and ADHD as well as treatment of the behavioral symptoms.

PMID- 8867272
TI  - [Hemodilution therapy with neuron metabolism specific therapy in ischemic stroke-
      encouraging results of a comparative study].
AB  - Treating ischemic stroke we could compare a (control-)group of 318 patients under
      up to date hemodilution therapy to a group of 100 patients receiving exactly the
      same treating scheme but including an add-on administering of Cerebrolysin. It
      proved a statistically validated better outcome within the Cerebrolysin add-on
      treated group evaluated by the Barolin-Neuro-Rehabilitation Scale. 1) More effect
      on social and occupational parameters than on motor functions, but also including
      some of those. 2) Cerebrolysin accelerates recovery and therewith offers better
      starting points for rehabilitation. As stroke is one of the main social-medical
      neuro-rehabilitation and gerontological problems of our days these results should
      be recognized in a general therapeutical use.

PMID- 8867273
TI  - [Transcranial magnetic stimulation in depressed patients: a new antidepressive
      therapeutic principle? Presentation of a pilot trial].
AB  - So far Transcranial Magnetic Stimulation (TMS) has been established as a
      technique for studying function of the pyramidal tract in diverse neurological
      diseases, being both safe and practically free from undesirable side-effects. 5
      depressive patients, diagnosed as ICD 9, 296.1 and 296.3 were treated with
      amitryptiline and TMS, either immediately at onset or as therapy-refractory
      patients up to 5 weeks after the beginning of their respective episodes. The
      results of this pilot study document a significant and swift decrease of
      depressive symptoms scored on the Hamilton rating scale. A single catatonic
      patient, ICD 9 295.7, presented a clinically impressive but transient improvement
      of her psychotic condition. Possible analogies between TMS and ECT are discussed
      as tentative hypotheses for the postulated efficacy of TMS. Further
      investigations seem warranted, as this method appears to be swift and effective
      in the treatment of depressive illness.

PMID- 8867274
TI  - [Drug therapy of activated arthrosis. On the effectiveness of an enzyme mixture
      versus diclofenac].
AB  - Clinical efficacy of the antiphlogistic potency of enzymes (Wobenzym, 4 x 7
      capsules/day) vs. Diclofenac-Na (2 x 50 mg capsules/day) on patients (n = 80)
      suffering from osteoarthritis of the knee in an acute phase was evaluated. The
      study design was double blind according to the GCP-guidelines. The treatment
      period lasted 28 days and was followed by a treatment-free controll-period of
      another 28 days. There was equal status of age, sex, duration and impact of
      osteoarthritis in both groups. The clinical parameters as pain at rest, on
      motion, on walking, at night and pain tenderness showed a significant improvement
      (p < 0.05) after the treatment period, with tendency to relapse in the following
      observation period. No significant difference between both treatment-groups could
      be seen. No changes in laboratory findings were observed. The global-assessment
      (physician's and patient's score) of efficacy and tolerability in both groups
      were mostly stated as "very good" and "good". Adverse events were reported as:
      Wobenzym: total 14 patients: gastrointestinal complaints (obstipation, vomiting,
      meteorism), allergic rash once and dizziness twice, 6 of these patients
      discontinued by that reasons. Diclofenac: total 11 patients: gastrointestinal
      complaints (epigastrical pain, upset stomach, meteorism), dizziness, 3 of these
      discontinued. All of these vanished after intake was stopped. Summarizing up it
      could be demonstrated that both evaluated drugs showed equal clinical potency. So
      it might be assumed that Wobenzym can be used as an alternative substance in
      treatment of acute painful osteoarthritis.

PMID- 8867275
TI  - [Irreversible coma and the physician's treatment responsibility].
AB  - Whether and how patients with clinically revealed persistant vegetative state
      (PVS) should be treated is a difficult question. In this paper the different
      approaches from maximum therapy to forego even nutrition and hydration are
      analysed and their underlying concepts examined. Within this context the official
      guidelines of the Swiss, the German as well as the British Medical Association
      are discussed.

PMID- 8867276
TI  - Roles of gastric GATA DNA-binding proteins.
AB  - The gastric H+/K(+)-ATPase is a P-type ATPase that is specifically expressed in
      gastric parietal cells and is responsible for acid secretion into the stomach. We
      have found one or more gastric mucosal nuclear proteins that recognize a sequence
      motif in the 5'-upstream regions of the H+/K(+)-ATPase alpha- and beta-subunit
      genes. This gastric motif, (G/C)PuPu(G/C)NGAT(A/T)PuPy, may be a binding site for
      a positive transcriptional regulator that functions specifically in parietal
      cells. We further demonstrated using cDNA cloning and in situ hybridization that
      novel zinc-finger proteins (GATA-GT1 and GATA-GT2) are present in the gastric
      parietal cells and bind to this motif. The proteins activate the transcription of
      the reporter gene with the 5'-upstream region of the H+/K(+)-ATPase beta-subunit
      gene. These results suggest that gastric GATA DNA-binding proteins have important
      roles in transcriptional activation of H+/K(+)-ATPase genes in the parietal
      cells.

PMID- 8867277
TI  - Modulation of membrane currents by cyclic AMP in cleavage-arrested Drosophila
      neurons.
AB  - A number of Drosophila learning mutants have defective intracellular second
      messenger systems. In an effort to develop techniques that will allow direct
      measurement of the effects of these mutations on whole-cell neuronal membrane
      currents, the perforated-patch whole-cell (PPWC) technique has been applied to
      cleavage-arrested cultured embryonic Drosophila neurons. This technique permits
      the measurement of membrane currents without disturbing the intracellular
      environment. As a result of the maintenance of the intracellular environment,
      Drosophila neuron currents are found to be much more stable than when measured
      using the conventional whole-cell (CWC) patch-clamp technique. Ca2+ channel
      currents, which typically 'wash out' within a few minutes of the beginning of CWC
      recording, are stable for the duration of the seal (tens of minutes) when
      measured using the PPWC technique. Since the learning mutations dunce and
      rutabaga disrupt cyclic AMP signalling, the action of externally applied
      dibutyryl cyclic AMP (db-cAMP) and theophylline on Ca2+ and K+ channel currents
      were studied. db-cAMP and theophylline enhanced the Ba2+ current, carried by Ca2+
      channels, but had no effect on the K+ current in the cleavage-arrested neurons.
      However, the large variability and reduction in density of Ba2+ and K+ currents
      raise questions about the suitability of using these cleavage-arrested cells as
      models for Drosophila neurons.

PMID- 8867278
TI  - Comparison of the responses to hypoxia, ischaemia and ischaemic preconditioning
      in wild marmot and laboratory rabbit hearts.
AB  - Marmots (Marmota flaviventris) are burrowing mammals that may be subjected to low
      levels of oxygen and high levels of carbon dioxide in their underground
      environment. Since marmots successfully deal with this physiological challenge,
      we hypothesized that the isolated perfused marmot heart would be damaged less and
      recover better from a bout of induced hypoxia or ischaemia than would the heart
      of a comparison animal, the New Zealand laboratory rabbit (Oryctolagus
      cuniculus). Isolated marmot and rabbit hearts were made hypoxic by a 30 min
      perfusion with an oxygen-deficient buffer. The hearts were then perfused with an
      oxygen-replete buffer and measurements of heart rate, left ventricular pressure
      and lactate dehydrogenase (LDH) release (an indicator of cell damage) were made
      over 5 or 10 min intervals for 30 min of hypoxia and 30 min of recovery. There
      were no species differences in the responses, except that the heart rate in
      marmots was about 50% of the rate in rabbits during the hypoxia part of the
      experiment. There was no evidence that the marmot hearts were damaged less or
      recovered better from hypoxia and reoxgenation than the rabbit hearts. Marmot and
      rabbit hearts were also subjected to 30 min of total ischaemia; measurements of
      heart rate, left ventricular pressure and LDH release were obtained during 30 min
      of reperfusion and compared with the pre-ischaemia values for these variables.
      There were no significant species differences. When the 30 min ischaemic period
      was preceded by a 5 min period of ischaemia and a 10 min reperfusion period
      (preconditioning), the rabbit hearts were protected by this brief ischaemic
      insult and recovered better than the hearts that had not been subjected to the
      preconditioning ischaemia. This was not true in the marmot hearts, however, as
      the preconditioning ischaemia did not promote a greater recovery over that in its
      absence. When preconditioned marmots hearts were compared with preconditioned
      rabbit hearts, there were no statistical differences in the responses. The
      hypothesis that marmot hearts would be damaged less and recover better from
      hypoxia and ischaemia was not supported by the experimental data.

PMID- 8867279
TI  - Immunofluorescent localization of constitutive and inducible prostaglandin H
      synthase in ovine astroglia.
AB  - We have used immunofluorescent techniques to examine the distribution of
      prostaglandin H synthase (PGHS) in ovine astrocyte-enriched secondary cultures
      and in mixed cortical cells in primary culture. A battery of monoclonal and
      polyclonal antibodies specific for the constitutive (PGHS-1) or inducible (PGHS
      2) forms of the enzyme were used to examine the cells in culture. Varying levels
      of PGHS-1 and PGHS-2-specific immunofluorescence were seen in astrocytes as well
      as in other cells. The fluorescent pattern and localization seen with antisera to
      both PGHS-1 and PGHS-2 were similar but were not identical. Both immunoreactive
      species were confined to nuclear and perinuclear regions of the cell, with no
      immunoreactivity evident in plasmalemma. In addition, PGHS-2-specific
      fluorescence was concentrated often as a homogeneous ring around the nucleus in
      heavily stained astrocytes. Mixed cortical glia/fibroblasts in primary culture
      were double labeled with antibodies to glial fibrillary acidic protein (GFAP) and
      to PGHS-2. GFAP and PGHS-2 were colocalized in clusters of astrocytes, but PGHS-2
      was evident in GFAP- cells as well. Cells treated with the mitogenic agent
      phorbol dibutyrate displayed more PGHS-2+ immunofluorescence compared to either
      vehicle control or cells pretreated with dexamethasone. We conclude that
      astrocytes cultured in serum express both constitutive and inducible forms of
      PGHS and that PGHS-2 is induced by mitogens in this cell type.

PMID- 8867280
TI  - Genesis of the adult retina and outer optic lobes of the moth, Manduca sexta. I.
      patterns of proliferation and cell death.
AB  - We have examined the development of the adult retina and the outer optic lobes in
      the moth Manduca sexta. The adult retina is generated from a group of epithelial
      cells lying within the larval head capsule between the larval ocelli and antenna.
      Proliferation of these cells begins during the feeding larval stage but
      accelerates at the end of the final larval instar. Proliferation occurs in two
      zones of mitotic activity; these zones flank a furrow in the presumptive retinal
      epithelium. The furrow and flanking mitotic zones migrate from posterior to
      anterior across the presumptive retinal epithelium. Posterior to the furrow,
      presumptive retinal cells from clusters and extend axons into the larval optic
      nerve. We have also examined the temporal patterns of neuronal proliferation and
      cell death during genesis of the adult outer optic ganglia, the medulla and the
      lamina. The medulla and the lamina are generated by distinct populations of
      neuroblasts in the outer optic analage; the neuroblasts divide asymmetrically to
      generate ganglion mother cells. Ganglion mother cells later divide symmetrically
      to generate immature neurons. Generation of the medulla cortex starts with the
      onset of the final larval instar, and cell death within the medulla cortex begins
      after the end of the final larval instar. Generation of the lamina cortex is
      initiated with the arrival of retinal afferents at the optic lobes, and cell
      death in the lamina cortex begins 1 day later. Generation of the outer optic
      ganglia terminates with the abrupt cessation of mitotic activity followed by
      degeneration of the outer optic anlage.

PMID- 8867281
TI  - Genesis of the adult retina and outer optic lobes of the moth, Manduca sexta. II.
      Effects of deafferentation and developmental hormone manipulation.
AB  - We have examined factors affecting neuronal proliferation and cell death during
      development of the adult outer optic ganglia in the moth Manduca sexta. The role
      of retinal afferents was addressed by optic nerve section on the first day of
      pupation, when the retina is only partially formed. Deafferentation by optic
      nerve section resulted in increased levels of cell death in the medulla cortex
      but did not affect medulla precursor proliferation. Conversely, division of
      lamina ganglion mother cells ceased following deafferentation, whereas cell death
      in the lamina cortex did not increase significantly. Implantation of isolated
      outer optic anlage into host animals demonstrated that medulla precursor
      proliferation was independent of centripetal inputs and retinal afferents. The
      role of developmental hormones in regulating outer optic ganglia development was
      also investigated. Many events in medulla and lamina development are correlated
      with changes in the titers of the ecdysteroids, and these events could be
      prevented by application of a juvenile hormone mimic (JHM). Application of JHM
      early in the fifth (final) larval instar terminated medulla precursor
      proliferation and prevented the initiation of lamina precursor proliferation, but
      application late in the fifth instar (after the commitment peak of ecdysteroids)
      had little effect on proliferation. Application of JHM on the third or fourth day
      of pupal life prolonged precursor proliferation and delayed degeneration of the
      outer optic anlage. Precocious application of 20-hydroxyecdysone on the first day
      of pupal life accelerated outer optic anlage degeneration but did not cause
      premature termination of proliferation.

PMID- 8867282
TI  - Individual axon morphology and thalamocortical topography in developing rat
      somatosensory cortex.
AB  - The morphology of individual thalamocortical axons in developing rat primary
      somatosensory cortex was studied using lipophilic tracers. Anterograde labeling
      with lipophilic dyes demonstrated a topographical organization of thalamocortical
      projections exiting the thalamus as early as embryonic day (E) 16; retrograde
      labeling studies demonstrated topography of these projections as they reached the
      cortex as early as E18. At E17, axons course tangentially within the intermediate
      zone and turn or branch near the deepest layer of cortex (layer VIb), suggesting
      the presence of guidance cues in this region. Axons appear to grow and branch
      progressively within layers VIb and VIa during the following days; axons in the
      intermediate zone may give rise to radially directed branches. Individual axons
      appear to grow steadily and progressively into the cortex, with the leading front
      of axons at the transition zone between the cortical plate (CP) and the
      differentiating cortical layers. At birth (P0), thalamocortical axons extend
      radially through layers VIa and V and emit branches within these layers; some
      axons reach the CP. By P1, layer IV has begun to differentiate and axons begin to
      form a few simple branches in the vicinity of the layer IV cells. Over the
      ensuing week, axons generate more branches within layer IV, but the tangential
      extent of individual axon arbors does not exceed the width of a barrel. By P7,
      individual axons overlap within barrel clusters, and individual axons span the
      width of a cluster. These observations indicate that thalamic afferents develop
      by progressive growth of arbors that remain spatially restricted, rather than by
      overbranching and retracting arbors.

PMID- 8867283
TI  - Topographical distribution of NADPH-diaphorase activity in the central nervous
      system of the frog, Rana perezi.
AB  - The distribution of NADPH-diaphorase (ND) activity was histochemically
      investigated in the brain of the frog Rana perezi. This technique provides a
      highly selective labeling of neurons and tracts. In the telencephalon, labeled
      cells are present in the olfactory bulb, pallial regions, septal area, nucleus of
      the diagonal band, striatum, and amygdala. Positive neurons surround the preoptic
      and infundibular recesses of the third ventricle. The magnocellular and
      suprachiasmatic hypothalamic nuclei contain stained cells. Numerous neurons are
      present in the anterior, lateral anterior, central, and lateral posteroventral
      thalamic nuclei. Positive terminal fields are organized in the same thalamic
      areas but most conspicuously in the visual recipient plexus of Bellonci, corpus
      geniculatum of the thalamus, and the superficial ventral thalamic nucleus.
      Labeled fibers and cell groups are observed in the pretectal area, the
      mesencephalic optic tectum, and the torus semicircularis. The nuclei of the
      mesencephalic tegmentum contain abundant labeled cells and a conspicuous cell
      population is localized medial and caudal to the isthmic nucleus. Numerous cells
      in the rhombencephalon are distributed in the octaval area, raphe nucleus,
      reticular nuclei, sensory trigeminal nuclei, nucleus of the solitary tract, and,
      at the obex levels, the dorsal column nucleus. Positive fibers are abundant in
      the superior olivary nucleus, the descending trigeminal, and the solitary tracts.
      In the spinal cord, a large population of intensely labeled neurons is present in
      all fields of the gray matter throughout its rostrocaudal extent. Several sensory
      pathways were heavily stained including part of the olfactory, visual, auditory,
      and somatosensory pathways. The distribution of ND-positive cells did not
      correspond to any single known neurotransmitter or neuroactive molecule system.
      In particular, abundant codistribution of ND and catecholamines is found in the
      anuran brain. Double labeling techniques have revealed restricted colocalization
      in the same neurons and only in the posterior tubercle and locus coeruleus. If ND
      is in amphibians a selective marker for neurons containing nitric oxide synthase,
      as generally proposed, with this method the neurons that may synthesize nitric
      oxide would be identified. This study provides evidence that nitric oxide may be
      involved in novel tasks, primarily related to forebrain functions, that are
      already present in amphibians.

PMID- 8867284
TI  - Contribution of thalamic input to the specification of cytoarchitectonic cortical
      fields in the primate: effects of bilateral enucleation in the fetal monkey on
      the boundaries, dimensions, and gyrification of striate and extrastriate cortex.
AB  - Bilateral enucleation was performed at different fetal ages during
      corticogenesis, and the brains were prepared for histological examination. Early
      enucleated fetuses (operated prior to embryonic day 77) showed morphological
      changes at the level of the thalamus and the cortex. In the thalamus, there was a
      loss of lamination and a decrease in size of the lateral geniculate nucleus.
      There was a decrease in the size of the inferior pulvinar, but there was no
      change in the lateral pulvinar. The border of striate cortex was as sharp in the
      enucleates as it was in the normal monkeys. In three of the four early
      enucleates, we observed an interdigitation of striate and extrastriate cortex. In
      three of the early enucleates, we observed a small island of nonstriate cortex
      near the striate border that was surrounded entirely by striate cortex.
      Enucleation led to an age-related reduction of striate cortex. This reduction was
      greater in the operculum than in the calcarine fissure. The reduction of striate
      cortex was accompanied by an increase in the dimensions of extrastriate visual
      cortex, so that the overall dimensions of the neocortex remained invariant. The
      extrastriate cortex in the enucleated animals presented a uniform
      cytoarchitecture and was indistinguishable from area 18 in the normal animal.
      There were changes in the gyral pattern that were restricted mainly to the cortex
      on the operculum. A deepening of minor dimples as well as the induction of a
      variable number of supplementary sulci led to an increase in the convolution of
      the occipital lobe. These results are discussed with respect to the specification
      of cortical areas. They demonstrate that the reduction in striate cortex was not
      accompanied by an equivalent reduction in the neocortex; rather, there was a
      border shift, and a large volume of cortex that was destined to become striate
      cortex appears to be cytoarchitectonically normal extrastriate cortex.

PMID- 8867285
TI  - Distribution of the calcium-binding proteins parvalbumin and calretinin in the
      auditory brainstem of adult and developing rats.
AB  - Parvalbumin (PV), calretinin (CR), and calbindin (CB) are calcium-binding
      proteins which are presumably involved in the regulation of the intracellular
      calcium concentration. Within the rat auditory system, CB is transiently
      expressed in several nuclei during the period of synapse refinement, indicating a
      specific function of CB during development, yet little is known in this regard
      about PV and CR. In order to gather more information about calcium-binding
      proteins during development, we analyzed the spatiotemporal distribution of PV
      and CR in the rat auditory brainstem using immunocytochemistry. In the adult, PV
      was heavily present in somata and neuropil of all nuclei and in fibers of all
      tracts. CR was found in somata of the cochlear nucleus and peripheral aspects of
      the inferior colliculus as well as in fibers extending into the superior olivary
      complex and the nuclei of the lateral lemniscus. The developmental expression of
      PV was characterized by a relatively late appearance in somata (at postnatal day
      8), followed by a rapid increase to adult levels. In contrast, CR
      immunoreactivity was already strong two days before birth, yet the number and
      intensity of labeled neurons subsequently decreased and CR disappeared almost
      completely in the superior olivary complex, nuclei of the lateral lemniscus, and
      central aspects of the inferior colliculus. These data, together with those on
      CB, show that CR, CB, and PV are sequentially expressed during auditory brainstem
      development. They also suggest that the presence of the three proteins can be
      correlated with definite developmental stages.

PMID- 8867286
TI  - Differential central projections of vestibular afferents in pigeons.
AB  - The question of whether a differential distribution of vestibular afferent
      information to central nuclear neurons is present in pigeons was studied using
      neural tracer compounds. Discrete tracing of afferent fibers innervating the
      individual semicircular canal and otolith organs was produced by sectioning
      individual branches of the vestibular nerve that innervate the different receptor
      organs and applying crystals of horseradish peroxidase, or a horseradish
      peroxidase/cholera toxin mixture, or a biocytin compound for neuronal uptake and
      transport. Afferent fibers and their terminal distributions within the brainstem
      and cerebellum were visualized subsequently. Discrete areas in the pigeon central
      nervous system that receive primary vestibular input include the superior, dorsal
      lateral, ventral lateral, medial, descending, and tangential vestibular nuclei;
      the A and B groups; the intermediate, medial, and lateral cerebellar nuclei; and
      the nodulus, the uvula, and the paraflocculus. Generally, the vertical canal
      afferents projected heavily to medial regions in the superior and descending
      vestibular nuclei as well as the A group. Vertical canal projections to the
      medial and lateral vestibular nuclei were observed but were less prominent.
      Horizontal canal projections to the superior and descending vestibular nuclei
      were much more centrally located than those of the vertical canals. A more
      substantial projection to the medial and lateral vestibular nuclei was seen with
      horizontal canal afferents compared to vertical canal fibers. Afferents
      innervating the utricle and saccule terminated generally in the lateral regions
      of all vestibular nuclei in areas that were separate from the projections of the
      semicircular canals. In addition, utricular fibers projected to regions in the
      vestibular nuclei that overlapped with the horizontal semicircular canal terminal
      fields, whereas saccular afferents projected to regions that received vertical
      canal fiber terminations. Lagenar afferents projected throughout the cochlear
      nuclei, to the dorsolateral regions of the cerebellar nuclei, and to lateral
      regions of the superior, lateral, medial, and descending vestibular nuclei.

PMID- 8867287
TI  - Selective upregulation of T alpha 1 alpha-tubulin and neuropeptide Y mRNAs after
      intermittent excitatory stimulation in adult rat hippocampus in vivo.
AB  - Adult central neurons exhibit significant structural and molecular changes in
      epilepsy. We have examined changes in two markers of morphological and
      physiological plasticity, T alpha 1 alpha-tubulin (T alpha 1) and neuropeptide Y
      (NPY) mRNAs, in response to intermittent (20 Hz, 10 seconds, 1 minute-1)
      stimulation of the rat perforant path in vivo. Stimulus trains elicited brief
      (0.5-3 seconds) afterdischarges in the ipsilateral dentate gyrus (DG). Four hours
      of stimulation caused no significant loss of inhibition in the DG 40-48 hours
      after stimulation ceased. However, it did lead to an increase in NPY mRNA in
      neurons of the ipsilateral and, to a lesser extent, contralateral DGs and Ammon's
      Horn. Many of these were presumably interneurons that normally express NPY.
      However, dentate granule cells (DGCs), which do not normally express this
      peptide, also expressed robust levels of NPY mRNA bilaterally. NPY mRNA levels
      peaked at 4-24 hours and returned to baseline by 48 hours poststimulation.
      Although 24 hours of stimulation induced a similar increase in interneurons, DGCs
      showed no detectable NPY mRNA. Afterdischarges were necessary to elevate NPY mRNA
      expression. Four hours of stimulation elevated T alpha 1 mRNA expression in both
      ipsilateral and, to a lesser extent, contralateral DGCs; this elevation peaked at
      24 hours poststimulation and declined to baseline by 72 hours. Stimulation for 24
      hours caused broader changes in T alpha 1 mRNA expression, with increases in DGCs
      and in CA3 pyramidal cells bilaterally. Acute denervation of the DG did not
      affect T alpha 1 mRNA level in the hippocampal formation. Elevated synaptic input
      resulting in afterdischarges, but not necessarily in excitability changes in the
      DG, led to alterations in the expression of molecular markers of plasticity.
      These changes may reflect adaptive responses to physiological activation.

PMID- 8867289
TI  - Microfabrication technology for DNA sequencing.

PMID- 8867288
TI  - Anatomy and targets of Dorsal Unpaired Median neurones in the Terminal Abdominal
      Ganglion of the male cockroach Periplaneta americana L.
AB  - The morphology of the Dorsal Unpaired Median (DUM) neurones in the Terminal
      Abdominal Ganglion (TAG) of the adult male cockroach Periplaneta americana were
      described based on wholemount preparations and paraffin sections and by using
      anterograde and retrograde cobalt mapping, octopamine-like immunohistochemistry,
      and double immunofluorescence technique with both conjugated gamma-aminobutyric
      acid (GABA) and octopamine antisera. Among 60 +/- 6 neurones with large somata
      (diameter 40 to 60 microns) on the dorsal midline surface of the TAG that were
      stained with toluidine blue, about 36 efferent DUM neurones exhibited octopamine
      like immunoreactivity. The DUM neurones were arranged in three clusters
      (anterior, median and posterior) corresponding to the 7th-11th abdominal ganglia
      of the fused TAG. Anterior efferent DUM neurones with one, two, and four pairs of
      lateral neurites entered segmental nerves VIIB; VIIB and phallic nerves; IXB and
      phallic nerves; VIIIA, IXA, X, and IX, respectively. Three octopamine-like
      immunoreactive DUM neurones innervating heart chambers via segmental nerves
      (VIIA, VIIIA, and IXA) in the last abdominal segments occurred within abdominal
      ganglia 7, 8, and 9. Together with octopamine-like immunoreactive efferent DUM
      neurones, GABA-like immunoreactive dorsal midline neurones with small somata (10
      to 20 microns) also occurred within the median group. The spatial distribution of
      DUM neurones in the TAG suggested that they had their origins in the median
      neuroblast, as for DUM neurones in the grasshopper.

PMID- 8867290
TI  - Third World participation in genome projects.

PMID- 8867291
TI  - High cell-density culture of Escherichia coli.
AB  - Escherichia coli is the most widely used prokaryotic system for the synthesis of
      heterologous proteins. Once an optimal expression system has been constructed,
      protein production can be enhanced by increasing the production of protein per
      cell per unit time (specific productivity), or by increasing the cell
      concentration per unit time (cell productivity). Various high cell-density
      culture (HCDC) techniques have been developed for growing recombinant and non
      recombinant E. coli strains in fed-batch cultures at concentrations greater than
      100 grams (dry cell weight) per liter. This article reviews the problems
      encountered in HCDC of E. coli, and discusses various solutions. Feeding
      strategies for HCDC of E. coli, and the results obtained using them, are also
      described.

PMID- 8867292
TI  - Effects of high and low shock energies on sinus electrograms recorded via
      integrated and true bipolar nonthoracotomy lead systems.
AB  - INTRODUCTION: The purpose of this investigation was to prospectively evaluate the
      voltage- and time-dependent characteristics of a biphasic defibrillator discharge
      on the amplitude of the rate sensing electrogram recorded from two "integrated"
      and one true bipolar nonthoracotomy lead system. Prolongation of redetection time
      has been noted after a failed first shock with nonthoracotomy lead systems.
      However, a prospective evaluation of the time- and voltage-dependent effects of
      biphasic shocks on electrogram amplitude with clinically utilized lead systems
      has not been systematically performed. METHODS AND RESULTS: Five- then 30-J R
      wave synchronous biphasic discharges were delivered during the supraventricular
      rhythm through three nonthoracotomy lead systems (Medtronic Transvene, Ventritex
      TVL, and CPI Endotak C 60 Series). The R wave amplitude was measured immediately
      postshock and for up to 1 minute. Amplitude changes were compared with preshock
      baseline value. A 5-J discharge had minimal effect on the R wave amplitude
      recorded from the three lead systems; however, 30 J resulted in significant
      diminution in R wave amplitude recorded from the integrated bipolar leads (in the
      Endotak lead to a greater extent than the TVL lead) with minimal effects on the
      Transvene lead. Following a 30-J discharge, the time constant for R wave recovery
      was 4.2, 14.9, and 15.3 seconds for Transvene, TVL, and Endotak 60 leads,
      respectively. CONCLUSION: There are voltage- and time-dependent reductions in
      postshock R wave amplitude. Integrated bipolar systems appear more affected than
      the "true" bipolar lead evaluated. This may be due, in part, to lead design,
      distance of distal defibrillating surface from rate sensing cathode, and the
      incorporation of the defibrillating surface as the rate sensing anode. The
      influence of post-shock R wave diminution on subsequent redetection remains
      speculative but may have implications for subsequent lead development.

PMID- 8867293
TI  - Management of ventricular fibrillation with transvenous defibrillators without
      baseline electrophysiologic testing or antiarrhythmic drugs.
AB  - INTRODUCTION: Baseline electrophysiologic study (EPS) is routinely performed in
      patients resuscitated from ventricular fibrillation (VF) to risk stratify and
      select patients for chronic antiarrhythmic drug therapy. The role of EP testing
      prior to insertion of a multiprogrammable implantable cardioverter defibrillator
      (ICD), however, is unclear. METHODS AND RESULTS: This study was a retrospective
      review of outcome in 66 survivors of an initial episode of out-of-hospital VF not
      associated with a Q wave myocardial infarction or reversible causes, treated with
      transvenous ICDs as first-line therapy. Patients were excluded from the study if
      they had a previous history of monomorphic ventricular tachycardia (VT), a
      clinical history suggestive of supraventricular tachycardia, or had undergone
      preoperative EP testing. Fifty-two of the patients (79%) were male with an
      average age of 58 +/- 11 years. Coronary artery disease was present in 43
      patients (66%), cardiomyopathy in 15 patients (23%), and valvular heart disease
      in 1 patient (1.5%). Seven patients (11%) had no detectable structural heart
      disease. The mean left ventricular ejection fraction was 0.40 +/- 0.16. With an
      average follow-up of 25 +/- 12 months, survival free of death from any cause was
      100%. Twenty-three patients (35%) experienced 48 episodes of recurrent rapid VT
      or VF (average cycle length: 236 +/- 47 msec) treated by their device. The mean
      time to first therapy was 223 +/- 200 days. Only one of these patients also
      received antitachycardia pacing for two episodes of VT. One patient (1.5%)
      temporarily received amiodarone after removal of an infected device that was
      subsequently replaced. No other patient received antiarrhythmic drug therapy.
      CONCLUSION: After a cardiac arrest due to primary VF, select patients treated
      with multiprogrammable ICDs can be managed successfully without baseline EPS or
      antiarrhythmic drug therapy.

PMID- 8867294
TI  - ICD implantation: cost conscious or patient conscious.

PMID- 8867295
TI  - Cardiac output is not affected during intraoperative testing of the automatic
      implantable cardioverter defibrillator.
AB  - INTRODUCTION: Perioperative mortality of patients undergoing implantation of
      automatic implantable cardioverter defibrillators (ICDs) has been reduced
      dramatically following the availability of transvenous-subcutaneous
      defibrillation leads. However, patients with severely reduced left ventricular
      function show a substantial rate of nonsudden cardiac mortality within the first
      year. Whether repeated intraoperative inductions of ventricular
      tachycardia/fibrillation (VT/VF) during implantation lead to hemodynamic
      deterioration and thus might contribute to development of end-stage heart failure
      in these patients is unknown. The purpose of the present study was to determine
      cardiac output and hemodynamic performance during transvenous-subcutaneous ICD
      implantation in patients with severe left ventricular dysfunction. METHODS AND
      RESULTS: In 11 patients with a left ventricular ejection fraction (EF) < or =
      0.35, cardiac output was measured automatically with a combined continuous
      cardiac output/mixed venous oxygen saturation pulmonary artery catheter system.
      ICD implantation was performed during standardized general anesthesia. In the 11
      patients (EF = 27 +/- 2% [mean +/- SEM]) a total of 95 episodes of VT/VF followed
      by defibrillation were induced (episodes per patient = 9 +/- 1; range 6 to 11).
      Cardiac index was 2.2 +/- 0.2 L.min-1.m-2 after induction of anesthesia (before
      start of surgery), and 1.9 +/- 0.1 L.min-1.m-2 immediately before first induction
      of VT/VF. After the last episode of VT/VF, cardiac index was 2.1 +/- 0.2 L.min
      1.m-2. Cardiac index measured 1, 2, and 3 minutes after induction of VT/VF was
      not significantly different when compared to the preinduction value during any
      episode of VT/VF induction. Similarly, stroke volume index was 39 +/- 5 mL.m-2
      immediately before first induction of VT/VF and 36 +/- 3 mL.m-2 after the last
      episode of VT/VF (NS). At the end of surgery, hemodynamic parameters did not
      exhibit any significant difference when compared to the data obtained before
      start of ICD implantation and testing. CONCLUSION: Extensive defibrillation tests
      during transvenous-subcutaneous ICD implantation in patients with severe left
      ventricular dysfunction are not associated with acute deterioration of cardiac
      performance.

PMID- 8867296
TI  - Phenylephrine-induced ventricular arrhythmias in dogs with inherited sudden
      death.
AB  - INTRODUCTION: Dogs with an inherited predisposition to sudden death display
      ventricular arrhythmias having certain characteristics, such as pause dependence,
      that are suggestive of early afterdepolarization-induced triggered activity. We
      hypothesized that alpha-adrenergic stimulation may facilitate the development of
      these arrhythmias by inducing a reflex bradycardia and by exerting a direct
      myocardial effect. METHODS AND RESULTS: Twenty affected dogs and 7 unaffected
      dogs were studied. The incidence and severity of ventricular arrhythmias were
      determined after administration of phenylephrine (0.01 mg/kg IV), with or without
      pretreatment with propranolol (0.1 to 0.3 mg/kg IV), atropine (0.04 mg/kg IV), or
      prazosin (0.5 mg/kg IV). Third-degree heart block was induced by AV nodal
      ablation in 4 affected dogs. Phenylephrine increased ventricular arrhythmias in
      affected dogs, with or without pretreatment with propranolol, but did not induce
      ventricular arrhythmias in unaffected dogs. In dogs with intact AV nodal
      conduction, atropine increased sinus rate, which suppressed baseline and
      phenylephrine-induced arrhythmias. In dogs with heart block, arrhythmias were
      increased during baseline and after phenylephrine, with or without pretreatment
      with atropine. Prazosin and overdrive ventricular pacing suppressed phenylephrine
      induced arrhythmias. CONCLUSION: Phenylephrine increases ventricular arrhythmias
      in dogs with inherited sudden death via both an induction of reflex bradycardia
      and a direct myocardial effect. Superimposition of heightened alpha-adrenergic
      and vagal tone may facilitate the development of sudden death in these animals.

PMID- 8867297
TI  - Myocardial vulnerability to T wave shocks: relation to shock strength, shock
      coupling interval, and dispersion of ventricular repolarization.
AB  - INTRODUCTION: Induction of ventricular fibrillation (VF) by T wave shocks is of
      clinical interest due to the correlation between the upper limit of vulnerability
      (ULV) and the defibrillation threshold (DFT). However, the ULV has not yet been
      defined precisely in reference to the entire "area of vulnerability" (AOV), which
      is defined bifunctionally by both shock strengths and shock coupling intervals,
      nor has it been related to the dispersion of ventricular repolarization,
      considered to be an important determinant of vulnerability. METHODS AND RESULTS:
      In 11 isolated perfused rabbit hearts immersed in a tissue bath containing a 3
      lead ECG recording system and two opposite plate electrodes for field shock
      administration, 7 monophasic action potentials (MAPs) were recorded
      simultaneously from different epicardial and endocardial regions of the right and
      left ventricles. An average of 90 +/- 25 monophasic waveform shocks of varying
      shock strengths and coupling intervals were delivered to each heart to determine
      the horizontal and vertical boundaries of the AOV. The AOV approximated a
      rhomboid with homogenous VF inducibility. The ULV and lower limit of
      vulnerability (LLV) represented discrete corners of the AOV with significant
      changes in VF inducibility if either shock coupling intervals or shock strength
      were changed by only 10 msec or 10 V, respectively (P < 0.001). The ULV occurred
      at 7 +/- 10 msec shorter coupling intervals than the LLV (P < 0.05), and VF
      inducing shock strengths at the left corner of the AOV were 50 +/- 67 V higher as
      compared to the right corner (P < 0.01). The maximal range of VF-inducing
      coupling intervals coincided (within < 2 msec) with the dispersion of MAPs at 70%
      repolarization, and the ULV coupling interval coincided (within < 4 msec) with
      the longest repolarization at 50%. CONCLUSIONS: (1) VF vulnerability to
      monophasic T wave shocks is defined by an AOV that has the shape of a leftward
      tilted rhomboid. (2) Both the ULV and LLV are sharply defined upper and lower
      corners of the AOV rhomboid. (3) The width of the AOV corresponds to the
      dispersion of ventricular repolarization at the 70% level. (4) Considering the
      dispersion of ventricular repolarization may yield more precise ULV
      determinations and a better understanding of the correlation between the ULV and
      DFT.

PMID- 8867298
TI  - Effects of heating with radiofrequency power on myocardial impulse conduction: is
      radiofrequency ablation exclusively thermally mediated?
AB  - INTRODUCTION: Although it is generally accepted that radiofrequency (RF) ablation
      causes exclusively thermally mediated effects, it has never been proved. METHODS
      AND RESULTS: In a previous report, temperatures required to induce conduction
      block in superfused canine epicardial ventricular myocardium were identified by
      exposure to heated superfusate: 50.3 degrees +/- 1.1 degrees C and 53.6 degrees
      +/- 0.6 degree C for transient and permanent block, respectively. In the present
      study, heating was performed using RF power in an otherwise identical model. Nine
      preparations from four dogs were used. A 1-cm diameter electrode was placed
      beneath the center of each preparation for RF delivery. Incisions were made to
      create a conductive isthmus over the ablation electrode. Preparations were paced
      to one side of the isthmus and electrograms recorded from the center of the
      isthmus and to either side. Temperature was measured using a miniature
      thermocouple located just below the epicardial surface, adjacent to the recording
      electrode in the heated zone. RF was delivered for 30 seconds at 5-minute
      intervals with increments in power per episode causing increments in temperature
      of approximately 2 degrees C. Temperature during pulses at which transient block
      occurred was 50.7 degrees +/- 3.0 degrees C; temperature at 30 seconds of heating
      in pulses leading to permanent block was 58.0 degrees +/- 3.4 degrees C.
      CONCLUSION: These findings provide evidence suggesting that the
      electrophysiologic effects of RF ablation are exclusively thermally mediated and
      are otherwise unrelated to the dissipation of high-frequency current.

PMID- 8867299
TI  - Functional bundle branch block as a delayed manifestation of retrograde
      concealment in the His-Purkinje system.
AB  - INTRODUCTION: The mechanism of functional bundle branch block induced at the
      onset of supraventricular tachycardia (SVT) is well established. However, no data
      exist to address the underlying mechanism of functional bundle branch block
      occurring in the second beat of SVT, when the first beat is conducted with a
      narrow QRS morphology and preceded by ventricular stimulation. METHODS AND
      RESULTS: Two patients showing such a phenomenon form the basis of this report.
      Patient 1 with AV nodal reentrant tachycardia of the common variety persistently
      demonstrated functional right bundle branch block in the second SVT complex when
      a short train of ventricular pacing was introduced during SVT. This occurred
      without any discernible change in the SVT cycle length. Patient 2 had a manifest
      posteroseptal accessory pathway and inducible orthodromic reentrant tachycardia.
      Functional bundle branch block during propagation of the second SVT complex
      invariably occurred either in the left bundle when SVT was induced by a bundle
      branch reentrant complex during premature ventricular stimulation, or in the
      right bundle when SVT was induced with a short train of ventricular pacing. The
      development of functional bundle branch block was preceded by minimal or no cycle
      length variations in the His-bundle inputs. CONCLUSION: These observations
      suggest that the type of functional bundle branch block occurring in the second
      SVT complex as a de novo phenomenon may be related to the relative timing of the
      retrograde penetration of the right versus left bundle during ventricular pacing
      or bundle branch reentrant complex. Therefore, due to its longest cycle length of
      activation and refractoriness, the earliest site of retrograde penetration is the
      most likely site of functional block during propagation of the second SVT
      complex. This delayed manifestation of retrograde concealment may provide new
      information regarding the electrophysiologic behavior of the His-Purkinje system.

PMID- 8867300
TI  - Irregular sinus parasystole due to intermittency and modulation of parasystolic
      activity.
AB  - A case of intermittent sinus parasystole in which the parasystolic focus is
      protected from the dominant sinus rhythm only during the second half of its
      intrinsic cycle is reported. In addition, a modulating (i.e., electronic) effect
      is often clearly exerted from the dominant rhythm upon the focus during the
      protected period. Coexistence of both modulation and intermittency in sinus
      parasystole, as well as a modulating effect limited to the second part of the
      parasystolic cycle, have not been previously reported.

PMID- 8867301
TI  - Origin of the sinus impulse.
AB  - It was generally accepted that the site of normal impulse origin within the atria
      was a single static focus within the sinus node. This review will examine how
      this model of impulse origin came about and has evolved. Early on, conflicting
      data suggested that the sinus node focus was not static and changed with
      interventions that changed heart rate, such as vagal stimulation. Furthermore,
      even with removal of the sinus node, a normal atrial rhythm was generated. High
      resolution mapping in humans and dogs showed that the initiation of the impulse
      was dynamic and could be multicentric, with more than one focus initiating a
      single beat. Shifts in the site of origin correlated with changes in rate and
      were consistent with P wave changes routinely observed in the standard ECG. These
      studies suggested multiple pacemakers were responsible for impulse initiation.
      However, it was not clear how these widespread pacemakers were coordinated to
      function synchronously. Recent canine data suggest that the node may be partially
      insulated from the surrounding atrium, resulting in multicentric origin starting
      from a single site within the node. What has evolved is a model of impulse origin
      with a sinus node having discrete exit sites and a dominant pacemaker within the
      node that can shift to other nodal sites. Complex and changing conduction out of
      the node, coupled with extranodal pacemakers, which can assume dominance over the
      node, combine with the autonomic nervous system to control heart rate and the
      pattern of impulse origin within the atria.

PMID- 8867302
TI  - Interfascicular macroreentry versus intrafascicular microreentry.

PMID- 8867303
TI  - An unusual pattern of AV conduction.

PMID- 8867304
TI  - Management of the patient with frequent discharges from implantable cardioverter
      defibrillator devices.

PMID- 8867305
TI  - [Ca(2+)-phospholipid-dependent protein kinases and their role in regulating
      metabolic processes].
AB  - The paper provides a broad overview of some information on Ca(2+)-phospholipid
      dependent protein kinases, their role in intracellular regulation. The data on
      enzyme functioning and regulatory properties are presented.

PMID- 8867306
TI  - [Alpha-fetoprotein: biochemical properties, function, and clinico-diagnostic
      significance].
AB  - The review is dedicated to the 30th anniversary of the opening and studying of
      alpha-fetoprotein (AFP). New data about molecular properties, structure and
      functions as well as regulation of AFP synthesis are presented. Clinical
      significance and prospects of the further study of this oncofetal glycoprotein
      has been discussed.

PMID- 8867307
TI  - [Features of noradrenaline stimulation of rat liver mitochondria respiration by
      ADP and calcium ions].
AB  - A single administration of a physiological dose of noradrenaline to animals. in
      contrast to adrenaline, stimulates the respiration of mitochondria not only under
      oxidation of FAD-dependent Krebbs cycle substrate of the succinase but also HAD
      dependent substrate of alpha-ketoglutarate. In the both cases the phosphorylation
      rate increases, since the action of noradrenaline, separating the respiration and
      oxidative phosphorylation, was not found. Noradrenaline increases the capacity of
      mitochondria to more actively absorb calcium ions under oxidation of succinate
      than under that of alpha-ketoglutarate.

PMID- 8867308
TI  - Stimulation of yeast EF-3 factor by mammalian ribosomes.
AB  - The ATPase activity of yeast elongation factor 3 (EF-3) which is a specific
      component of fungal translational machinery and normally requires homological
      ribosomes, can be stimulated by mammalian ribosomes (from the rabbit liver). The
      level of such heterological stimulation is strongly dependent on ATP
      concentration and the ratio of ribosomes to EF-3 and achieves 50% of homological
      one under optimum conditions. ATP concentration dependence, modes of inhibition
      by ADP and pH-dependence have been found to differ for EF-3 activity stimulated
      by ribosomes and rabbit ribosome-associated ATPase. It may reflect the necessity
      of [EF-3*ATP*Rs]-complex formation while in the case of ribosomal ATPase both
      catalytic center and the enhancement element are located in the ribosome. Both
      40S and 60S subunits take part in stimulation, contrary to the homological
      system, where only 40S subunits play crucial role in this process. The data
      presented indicate that the binding site and enhancement element(s) for EF-3 in
      the ribosomes are concerved in evolution, though with a significant change in the
      binding affinity.

PMID- 8867309
TI  - [Effect of reproduction of the LPP-3 cyanophage on glutamate dehydrogenase and
      glutamine synthetase activity in the cyanobacterium Plectonema boryanum].
AB  - The effect of cyanophage LPP-3 reproduction on glutamate dehydrogenase and
      glutamine synthetase (GS) in P boryanum cells have been studied. It was
      determined that the both reactions are intensified by 135% and 220%, accordingly.
      Isoenzymes of GS were purified from native and infected cell of cyanobacteria.
      Their physical-and-chemical properties are different. The cyanophage development
      probably causes specific modification of the cell enzymes.

PMID- 8867310
TI  - [Comparative characteristics of membrane forms of aldehyde dehydrogenase].
AB  - It was demonstrated from the results of kinetic analysis that acetaldehyde
      oxidation reaction, which is catalyzed by membrane isoenzyme forms of
      mitochondrial and microsomal aldehyde dehydrogenases, has the ordered Bi-Bi
      mechanism. An attempt was made to compare the active site structures of these two
      isozyme forms using cyclopropylethyl-containing benzoic acid amides which are the
      reversible inhibitors of the studied enzyme activity. The amides competitively
      inhibited each enzyme activity relative to acetaldehyde. The inhibition constant
      values were calculated. As to NAD+ partially competitive type of inhibition was
      observed for aldehyde dehydrogenase of the microsomes. At low amide
      concentrations the mitochondrial aldehyde dehydrogenase was inhibited
      uncompetitively. With increased concentration of the compounds over 75 microM the
      character of inhibition by 2.4-dichlorine- and 2.4-dichlorine-5-methylbenzoic
      acid amides changed to mixed one; and when using the amides of 2.5-dichlorine-4
      methylbenzoic acid it changes for pseudoinhibition. The difference of kinetic
      behaviour of the studied compounds with aldehyde dehydrogenase membranes forms
      suggests the conformation similarity of the sites for binding acetaldehyde for
      the both enzymes and distinction of the sites for coenzyme binding.

PMID- 8867311
TI  - [Combined effect of Pb2+ and divalent mental complexes on superprecipation and
      ATPase activity of myometrial actomyosin].
AB  - The inhibiting effect of Pb2+ (0.1-1.0 mM) on superprecipitation and ATPase
      activity of myometrium actomyosin has been shown. It is found out that of 11
      studied chelators of bivalent cations only monosodium salt of 4-guanidino-1
      hydroxybutyliden-1.1-bisphosphonic acid can efficiently renews the value of
      superprecipitation and ATPase activity of actomyosin in presence of lead ions. It
      is supposed that this renewal is underlied by binding of guanidin group of Pb
      ions.

PMID- 8867312
TI  - [A conductometric enzymatic glucose sensor. A search for ways to improve
      analytical characteristics].
AB  - Characteristics of conductometric enzyme glucosensor based on thin-film
      interdigitated electrodes have been studied. The obtained biosensor exhibits a
      linear dynamic range of 0.01-2 mM for glucose and sensitivity 5 microS/min*mM for
      kinetic mode of measurements and 8 microS/mM for steady-state mode of
      measurements. Additional 2% PVB- and NAFION-membranes are suggested for the
      extension of the dynamic range. This permits extending the dynamic range of the
      sensor up to glicose concentration of 10 mM. Dependence of activity of
      immobilized enzyme on ionic strength and buffer capacity of the solution has been
      studied. It was shown that formation of additional membranes results in the
      substantial reduction of the buffer concentration effect on the sensor response.
      The obtained results are interpreted in terms of permselective properties of the
      additional membrane formed.

PMID- 8867313
TI  - Identification and characteristic of LDL-subfractions in human plasma.
AB  - Density gradient ultracentrifugation and high resolution polyacrylamide gel
      electrophoresis (Lipoprint LDL-system) were used to examine the discrete LDL
      subfraction patterns in normal and hyperlipidemic patients. Two new programs for
      LDL and VLDL subfractions were elaborated and a new method of evaluation for
      cholesterol content in LDL-subfractions, based on area distribution ratio of
      densitograms without density gradient ultracentrifugation, was created. The
      predominance of cholesterol and triglycerides in dense LDL3-subclass (d-1,048
      1,063 g/ml) under hypercholesterolemia and hypertriglyceridemia was found.
      Lipoprint LDL-electrophoresis method was developed for the characteristic of
      lipemic state of organism and detection and quantitation of plasma LDL
      subfractions.

PMID- 8867314
TI  - [Some characteristics of metabolism in osteoarticular, cardiovascular, and liver
      tissues in "experimental osteochondrosis"].
AB  - Considerable changes of collagen, glycosaminoglycans and calcium were observed
      both in vertebral tissues, bone, and in the heart, vessels, liver during
      development of "experimental osteochondrosis". The results have shown, that
      desintegration of biochemical processes in different tissues may be one of the
      factors affecting several diseases in one organism.

PMID- 8867315
TI  - [Increase in thyroxine level in blood plasma of hypothyroid rats after
      administering histones].
AB  - It has been shown that the administration of total histones (H1, H3, H2B, H2A,
      H4), the total histones without histones H4 (H1, H3, H2B, H2A), H1 histones at
      concentrations of 0.001 and 1 microgram per 100 g of body weight (low and high
      concentrations) to intact rats during 6 days leads to the decrease of T4 amount
      in the blood plasm. The total histones and histone H1 at low concentration
      decrease the T4 amount by the coefficients 5.2 and 5.8 respectively. The
      corresponding coefficients for high concentration are 2.6 and 1.2. There is no
      difference in the action of the total histones and H1 histone at low
      concentration. Low concentration of histones is more effective for the decrease
      of T4 amount than the high one or than the antithyroid agents mercasolyl and LiCl
      (3 mg and 2 mM per .100 g of body weight), which decrease the amount of T4 in
      intact rats by the coefficient 3.6 in 38 days. Administration of histones
      decreases the amount of T4 in the intact rats but, on the contrary, the 3-4 fold
      increase is observed in hypothyroid rats, so the amount of T4 is practically
      reverted to the level of intact rats. The mechanism of regulation of the amount
      of T4 by histones is discussed.

PMID- 8867316
TI  - [Effect of ionizing radiation and physical loads on pyrimidine-5'-nucleotidase
      activity in rat liver subcellular fractions].
AB  - Activity of pyridine-5'-nucleotidase in the mitochondria and postmitochondrial
      supernatant of the rat liver has been studied as affected by the radiation and
      physical load (running till tiredness). It is shown that physical load leads to
      double increase of cytidinemonophosphatase activity and does not actually affect
      uridine monophosphate one. Irradiation evokes changes of cytidine monophosphatase
      activity of the studied fractions in time: 1 year after irradiation it increases
      by 45%, 1 day later it sharply changes and 3 days later it increases again.
      Mutual action of the irradiation and physical loading 1 year after the
      irradiation causes the decrease of uridine monophosphatase and cytidine
      monophosphatase activity and 3 days later their amount increases, especially in
      the postmitochondrial supernatant (2-53 times). Thus the data obtained show that
      the effect of the radiation and physical loading evoke rather essential and
      stable changes in the activity of key enzymes of uridine monophosphate and
      cytidine monophosphate.

PMID- 8867318
TI  - Methazid-induced vitamin B2 deficiency in rats and its prevention.
AB  - It has been estimated that ten-day rectal administration of metazid in the form
      of suppositories (20 mg per 100 g of body mass) gives rise to vitamin B2
      deficiency both in rats with initial vitamin B2 insufficiency and in those
      adequately supplied. This is confirmed by a decrease in the vitamin B2 content
      both in the liver and in the blood plasma. Development and use of suppositories
      containing combined preparation of metazid and riboflavin (in the dose of 100
      micrograms per a rat according to the daily recommended allowance) completely
      prevent metazid-induced vitamin B2 deficiency.

PMID- 8867317
TI  - [Effect of hyperbaric conditions on liver monoamine oxidase activity in Komandor
      squid and mice].
AB  - Liver monoamineoxidase of Berryteuthis magister has been first studied for its
      activity and substrate specificity. Valid decrease of monoamineoxidase activity
      has been observed in the preparation obtained from the mouse liver by three
      studied substrates (serotonine, tyramine, benzylamine) as affected by high
      pressure (101 at; helioxygen mixture and hydrostatical conditions). At the same
      time, monoamineoxidase activity in the preparation isolated from Berryteuthis
      magister liver did not change under such conditions. Such stability of the liver
      enzyme of Berryteuthis magister dwelling under natural conditions under the
      effect of high pressure is treated from the viewpoint of biochemical adaptation.

PMID- 8867319
TI  - [Superoxide dismutase activity in microsomes of functionally different rat
      tissues in vitamin E deficiency].
AB  - Comparative investigation of microsome superoxide dismutase activity in
      functionally different rat tissues such as lung and liver has been carried out.
      Modification of superoxide dismutase fraction isolated from lung and liver
      microsomes and SOD-activity evaluation by means of superoxide radical-dependent
      pyrogallol autooxidation method have been described in detail. SOD-activity has
      been shown to be connected with the degree of lipid peroxidative oxidation (LPO)
      and total condition of tissue antioxidative system in case of different E-vitamin
      security in various functional types of cells (alveolocytes and hepatocytes).

PMID- 8867320
TI  - [Effect of glucocorticoids on activity of soluble and membrane-bound forms of
      carboxypeptidase H in vivo].
AB  - Inhibition of soluble and membrane-bound carboxypeptidase H in rat hypothalamus,
      striatum and pituitary gland by hydrocortisone and dexamethasone treatment in
      vivo has been established. Differences in the dynamics of change in the activity
      were determined by the action of hydrocortisone and dexamethasone. Differences of
      the dynamics of change in soluble and membrane-bound carboxypeptidase H activity
      were also observed. Possible causes of these differences are discussed.

PMID- 8867321
TI  - [Distribution of certain nonelectrolytes between intra- and extracellular parts
      of erythrocytes].
AB  - Human red blood cells were balanced at 37 degrees C in 15% solution of the
      following nonelectrolytes (NE): methanol, ethanol, 1,2-propanediol, diethylene
      glycol, glycerol, polythelene glycols (PEGs) with molecular masses 300, 400, 600,
      1000, 15000. The distribution coefficients (Q) equal to the ratio of the N
      concentration in cell to that in the intercellular medium, were determined by 1H
      NMR technique. A monotonous decrease of the Q values with the increase of the
      molecular mass of the NE from 1.15 + 0.12 for methanol to 0.12 +/- 0.01 for PEG
      1500 has been demonstrated. Results obtained demonstrate that the mixture (PEG)
      components with different molecular weights and 1,2-PD-PEG-1500 take negligible
      influence on the distribution coefficients of these substances between
      erythrocytes and extracellular environment.

PMID- 8867322
TI  - [Interaction between lipid peroxides, the antioxidant system, and levels of
      cyclic AMP and cyclic GMP in hypoxic and hyperthermic animals].
AB  - The hypoxic syndrome as the basis of pathothenesis of the mine trauma was studied
      in experiments on rats. It is established that the latter determines sharp
      activation of the processes of lipid peroxidation and weakening of the basic
      components of antioxidant system of the organism with simultaneous accumulation
      of leucotrienes B4 in the blood plasma. Besides, the disbalance in the content of
      secondary messengers--cAMP an cGMP has been established.

PMID- 8867323
TI  - [Effect of enomelanin on lipid peroxidation and the glutathione system in rat
      lung tissue exposed to NO2].
AB  - Effect of preliminary intraperitoneal injection on the state of the glutathione
      system and lipid peroxidation intensity in the lungs of rats subjected to NO2 has
      been studient. This compound is shown to decrease significantly all lipid
      peroxidation processes and to inhibit completely glutathion oxidation. These
      effects are supposed to be a result not only of antioxidant properties of
      enomelanin, but also of its ability to promote a decrease in the activity of
      glutathione-depending enzymes subjected to NO2.

PMID- 8867324
TI  - New approaches in molecular structure prediction.
AB  - In the past years, much effort has been put on the development of new
      methodologies and algorithms for the prediction of protein secondary and tertiary
      structures from (sequence) data; this is reviewed in detail. New approaches for
      these predictions such as neural network methods, genetic algorithms, machine
      learning, and graph theoretical methods are discussed. Secondary structure
      prediction algorithms were improved mostly by considering families of related
      proteins; however, for the reliable tertiary structure modeling of proteins,
      knowledge-based techniques are still preferred. Methods and examples with more or
      less successful results are described. Also, programs and parameterizations for
      energy minimisations, molecular dynamics, and electrostatic interactions have
      been improved, especially with respect to their former limits of applicability.
      Other topics discussed in this review include the use of traditional and on-line
      databases, the docking problem and surface properties of biomolecules, packing of
      protein cores, de novo design and protein engineering, prediction of membrane
      protein structures, the verification and reliability of model structures, and
      progress made with currently available software and computer hardware. In
      summary, the prediction of the structure, function, and other properties of a
      protein is still possible only within limits, but these limits continue to be
      moved.

PMID- 8867325
TI  - Characteristics of current induced potential oscillations of a triolein
      impregnated membrane placed between identical salt solutions.
AB  - Periodic oscillations of electric potential were induced by DC electric current
      between identical salt solutions separated by a membrane filter impregnated with
      triolein. The oscillation period was controlled by the base electric potential,
      and temperature dependence of base conductance and conductance amplitude were
      both close to that of the electric conductivity of the aqueous salt solution.
      Effects of salt concentration on membrane conductance and on oscillation
      characteristics were experimentally investigated, and the lifetime of the
      membrane and of each oscillation were much improved by regulating the
      concentration of the salt solution. Moreover, characteristics of oscillation
      curves could be controlled. All the experimental results could be explained by a
      model where the oscillation was generated by a periodic change of the diameter of
      a hole through the membrane, which opened in one of the pores filled with
      triolein.

PMID- 8867326
TI  - Mechanism of the long tail-fiber deployment of bacteriophages T-even and its role
      in adsorption, infection and sedimentation.
AB  - Models for the tail-fiber deployment of T-even bacteriophages have been
      experimentally tested by correlating sedimentation constants, adsorption rates,
      protease inactivation kinetics, and fiber configurations of individual phages
      observed by electron microscopy. Neither the collective nor the individualistic
      model, i.e. coordinated fiber retraction and expansion or oscillation of fibers
      independently of each other, respectively, could satisfactorily account for the
      results presented. We propose a new intermediary model, in which the base-plate
      determines a collective behaviour by fixing the hinge angle, around which
      individual fibers oscillate freely. The bidisperse, so-called dual sedimentation
      was shown to occur mainly with nascent high-concentration phage stocks in
      potassium glutamate containing media. Indeed, when mature intracellular phages
      are released in 0.5 M potassium glutamate--a condition simulating the
      intracellular environment--only the fast form appears. Upon storage in the cold
      or release into 0.5 M chloride, both forms appear. Results confirming that the
      sedimentation constants of the fast and slow form roughly correspond to those of
      the monodisperse sedimentation, characteristic of the extreme pH values, i.e. 5
      and 8, do not allow to conclude that fiber configuration is the only cause of the
      bidisperse sedimentation.

PMID- 8867327
TI  - A molecular theory of cartilage viscoelasticity.
AB  - Recent work on the subject of cartilage mechanics has begun to focus on the
      relationship between the microscopic structure of cartilage and its macroscopic
      mechanical properties (Bader et al., Biochem. Biophys. Acta, 1116 (1992) 147-154;
      Buschmann, PhD Thesis, Massachusetts Institute of Technology, 1992; Kovach,
      Biophys. Chem., 53 (1995) 181-187; Lai et al., J. Biochem. Eng., 113 (1991) 245
      248; Armstrong and Mow, J. Bone Jt. Surg., 64A (1982) 88; Jackson and James,
      Biorheology, 19 (1982) 317-330). This paper reviews recent theoretical
      developments and presents a comprehensive explanation of the viscoelastic
      properties of cartilage in terms of molecular structure. In doing this, a closed
      form hybrid solution to the non-linear, cylindrical Poisson-Boltzmann equation is
      developed to describe the charge-dependent component of the equilibrium
      elasticity arising from polysaccharide charge (Benham, J. Chem. Phys., 79 (4)
      (1983) 1969-1973; Einevoll and Hemmer, J. Phys. Chem., 89 (1) (1988) 474-484;
      Fixman, J. Chem. Phys., 70 (11) (1979) 4995-5001; Ramanathan and Woodburg, J.
      Chem. Phys., 82 (3) (1985) 1482-1491; Wennerstrom et al., J. Chem. Phys., 76 (9)
      (1982) 4665-4670). This solution agrees with numerical solutions found in the
      literature (Buschmann, PhD Thesis, Massachusetts Institute of Technology, 1992).
      The charge-independent, entropic contribution to the equilibrium elasticity is
      explained in a manner similar to that recently presented for concentrated
      proteoglycan solution (Kovach, Biophys. Chem., 53 (1995) 181-187). This approach
      exploits a lattice model of the solution, subject to a Bragg-Williams type
      approximation to derive the volume dependence of polysaccharide configuration
      entropy (Flory, Principles of Polymer Chemistry, Cornell University Press,
      Ithaca, NY, 1953; Huggins, Some properties of Solutions of Long-chain Compounds,
      1941, pp. 151-157; Stanley, Introduction to Phase Transitions and Critical
      Phenomena, Oxford University Press, Oxford, 1971). Together, these two
      contributions accurately reproduce the experimentally determined osmotic pressure
      of cartilage as previously determined by Maroudas (Maroudas and Bannon,
      Biorheology, 18 (1981) 619-632). The time-dependent, or creep, phenomena which
      cartilage exhibits when subject to mechanical load is explained in terms of
      frictional drag on the polysaccharide chain monomers in terms of a Kirkwood
      Riseman type model (Kirkwood and Riseman, J. Chem. Phys., 16 (6) (1948) 573-579).
      This approach is shown to accurately predict the hydraulic permeability of
      cartilage as previously determined by Maroudas (Madouras, Ann. Rheum. Dis., 34
      (suppl. 3) (1975) 77). By use of a quasi-static approximation (neglecting
      inertial effects) the time-dependent response to a uniform compressive force is
      determined and also found to be in good agreement with experimental values from
      the literature.

PMID- 8867328
TI  - Regulation of cytochrome oxidase: theoretical studies.
AB  - Using the dynamic model of oxidative phosphorylation developed previously and
      tested for its validity under a broad range of conditions some properties of
      cytochrome oxidase in the whole system considered were simulated. The regulation
      of this enzyme by oxygen concentration, delta p and reduction level of cytochrome
      c were studied. Assuming at least qualitative validity of the model, the
      following conclusions were drawn: (1) Regulation of cytochrome oxidase is
      different under the same conditions, when changes in the system (oxidative
      phosphorylation in isolated mitochondria) are imposed by a decrease in oxygen
      concentration (aerobiosis-->anaerobiosis transition) or by addition of hexokinase
      (state 4-->state 3 transition). In the former case, cytochrome c and delta p play
      a very similar role in the compensation for a decrease in the respiration rate
      caused by lowered oxygen concentration, while in the latter case changes in delta
      p activate cytochrome oxidase much stronger than changes in the reduction level
      of cytochrome c. (2) There is no unique thermodynamic flux-force relationship for
      cytochrome oxidase. This relationship depends on how the thermodynamic span of
      the reaction catalyzed by this enzyme is changed (aerobiosis-->anaerobiosis
      transition vs. state 4-->state 3 transition). (3) Under some conditions
      (aerobiosis-->anaerobiosis transition) the flux-force relationship can be
      inverse, i.e. increase in a thermodynamic force occurs simultaneously with
      decrease in a reaction rate.

PMID- 8867329
TI  - Self-sustained pH oscillations in immobilized proteolytic enzyme systems.
AB  - This work represents our first step toward fulfilling the need to discover a
      model system for experimental investigations of temporal oscillations, pattern
      formations, and other non-linearity related dynamic behavior in immobilized
      enzyme-membrane systems. In this paper, the regions in the parameter space where
      self-sustained pH oscillations can be induced were determined via extensive
      numerical simulation for five enzyme-membrane systems involving four proteolytic
      enzymes: alpha-chymotrypsin, trypsin, bromelain, and ficin. From this study, we
      concluded that, even with current enzyme-immobilization techniques, the
      possibility of experimentally observing self-sustained pH oscillations in a flat
      membrane immobilized with alpha-chymotrypsin and using N-acetyl-L-tryptophan
      ethyl ester as a substrate is high. Under suitable conditions and with extra
      efforts, self-sustained oscillations may also occur in membrane systems
      immobilized with ficin, trypsin and bromelain.

PMID- 8867330
TI  - Electronic energy levels and hopping conductivity of an entire molecule of
      hagfish insulin.
AB  - The quantum-chemical calculation of an entire molecule of hagfish insulin was
      done by the ENFC method in which the matrix elements were calculated at the ab
      initio level using a minimal basis set with simulation of the aqueous solution
      environment. The ac conductivity for hagfish insulin was also calculated at the
      ab initio level by random walk theory. All the results were compared with those
      of pig insulin. It is shown that the reduction of HOMOs and LUMOs localized on
      the active sites of hagfish insulin agrees with the decrease in the biological
      reactivity of the insulin. The analysis of primary hopping events showed that a
      different sequence could influence the biological activity of insulin through the
      distribution of the hopping centers and the quantities of the hopping
      frequencies. The curve of the frequency versus ac conductivity of hagfish insulin
      shows that the different amino acid sequences of proteins influence the hopping
      conductivity. However, the electronic properties of native proteins are dominated
      by the three-dimensional conformations. Finally, the electronic mechanism of
      trans-membrane signal transforms by insulin and its receptor, which had been
      proposed by Ye and Ladik, was clearly described.

PMID- 8867331
TI  - Oxygen binding to fallow-deer (Dama dama) hemoglobin: stepwise enthalpies at pH
      7.4.
AB  - High-precision thin-layer gas-solution microcalorimetry has been used to study
      the oxygen binding properties of fallow-deer (Dama dama) hemoglobin under
      physiological conditions. This method measures directly the enthalpy of
      macromolecular ligand binding by changing the ligand activity in a manner
      analogous to that of the Gill thin-layer optical apparatus ([1], D. Dolman and S.
      J. Gill, Anal. Biochem., 87 (1978) 127-134). By logarithmically lowering the
      partial pressure of oxygen we have generated differential heat binding curves of
      oxygen binding to fallow-deer hemoglobin in phosphate buffer at pH 7.4. In order
      to enlarge the data field, the temperature dependence of the oxygen affinity was
      examined by generating binding curves at a number of different temperatures
      allowing for separation of enthalpy and free energy parameters. This type of
      experimental analysis makes no assumption of optical linearity between the
      various heme groups and reveals initially that overall oxygen binding to fallow
      deer hemoglobin is less exothermic and of lower affinity than for human
      hemoglobin A0. In addition, previous optical work on the ancestrally related
      reindeer hemoglobin (Rangifer tarandus; [2], B. Giardina, O. Brix, M. Nuutinen,
      S. Sherbini, A. Bardgard, G. Lazzarino and S. Condo, FEBS Lett., 247 (1989) 135)
      has indicated that the enthalpy associated with its final two oxygen binding
      steps is minimal. Our calorimetric determination with fallow-deer hemoglobin also
      reveals this tendency. Presumably, this adaptation would make it easier for these
      animals to maintain a consistent hemoglobin oxygen saturation level under
      environmental conditions where the temperature fluctuates.

PMID- 8867332
TI  - Fluorescence emission and anisotropy from rhodamine dimers.
AB  - The absorption, fluorescence emission, and excitation fluorescence anisotropy
      spectra of a rhodamine dye in a water-glycerol solution at high concentration
      were investigated to determine spectroscopic properties of the ground state
      dimer. The combination of data from these spectra measured at several dye
      concentrations contained sufficient constraints on the model for dimer
      association to permit an estimate of: the association constant, the extinction
      coefficients, the relative fluorescence quantum yield, and the emission spectra
      of the monomeric and dimeric species. The rhodamine dimer is an efficient
      fluorescence emitter with fluorescence anisotropy equivalent to that of the pure
      monomeric species over the range of excitation wavelengths covering its two
      lowest energy transitions.

PMID- 8867333
TI  - Binding of Ru(II) polyazaaromatic complexes to DNA: A 23Na NMR spin-lattice
      relaxation study.
AB  - The possibility of using sodium-23 spin-lattice relaxation rate measurements to
      probe the interaction modes of Ru11 polyazaaaromatic complexes with DNA is
      investigated. The following complexes are considered: Ru(phen)3(2+) (phen = 1.10
      phenanthroline), Ru(phen)2HAT2+ (HAT = 1,4,5,8,9,12-hexaazatriphenylene), and
      Ru(diMeTAP)3(2+) (diMeTAP = 2,7-dimethyl-1,4,5,8-tetraazaphenanthrene). The
      addition of Ru(diMeTAP)3(2+) to a solution of NaDNA leads to a decrease in the
      sodium-23 spin-lattice relaxation rate (R1) similar to the effect observed upon
      addition of Mg2+. This indicates that Ru(diMeTAP)3(2+) interacts like Mg2+ with
      DNA and consequently that the electrostatic interaction dominates the association
      with DNA, Ru(phen)3(2+) and Ru(phen)2HAT2+ diminish R1 more efficiently than
      Mg2+, in a manner similar to ethidium bromide, which is known for its
      intercalation properties. Thus interactions other than electrostatic occur
      between these two complexes and DNA. These results are in agreement with data
      obtained from other techniques, according to which Ru(phen)3(2+) and
      Ru(phen)2HAT2+ are located partially inside the DNA double helix, in contrast to
      Ru(diMeTAP)3(2+) which remains in the ionic atmosphere around the phosphate
      backbone.

PMID- 8867334
TI  - Monte Carlo study for fluctuation analysis of the in vitro motility driven by
      protein motors.
AB  - The fluctuation properties of the sliding movement of an individual cytoskeletal
      filament driven by protein motors in vitro can be analyzed by calculating the
      mean-square deviation of the displacement from the average within its single
      trajectory. For this purpose, a Monte Carlo simulation was used to define the
      conditions and limitations of a method for smoothing (curved) noisy trajectories
      without affecting either the steady or fluctuation characteristics inherent to
      the individual filament sliding movement. By applying the method to real
      experimental trajectory data, we show that an effective diffusion coefficient
      from displacement fluctuations of a sliding filament can be obtained from its
      single noisy trajectory even when it is curved.

PMID- 8867335
TI  - Thermodynamics of the interactions of sanguinarine with DNA: influence of ionic
      strength and base composition.
AB  - Using a combination of spectrophotometric and spectrofluorimetric techniques, we
      report the first thermodynamic characterization of sanguinarine binding to a
      series of natural and synthetic host DNA duplexes over a wide range of
      temperature and sodium concentration. The binding isotherms fit reasonably well
      to the neighbour exclusion model. The salt and temperature dependence of the
      binding constants is used to estimate the thermodynamic parameters involved in
      the interaction of the alkaloid with DNA. The resulting binding data are found to
      be sensitive to the ionic strength of the medium, base composition and sequence
      of base pairs. When the sodium ion concentration is increased from 0.005 M to 0.5
      M, the binding free energy changes vary in a range from -8.47 to -7.1 kcal mol-1,
      which corresponds to a binding constant range from 1.85 x 10(6) to 1.8 x 10(5) M
      1 at 20 degrees C. More distinct is the spread in the binding enthalpy changes
      which range from -6.35 to -2.62 kcal mol-1 corresponding to binding entropy
      changes from +7.22 to +15.3 cal K-1 mol-1 at 20 degrees C. On the other hand when
      the GC content of the host DNA duplexes is increased, the binding free energy
      varies in a range from -7.28 to -8.58 kcal mol-1 with the binding enthalpy
      changes ranging from -0.46 to -14.31 kcal mol-1, while corresponding binding
      entropy changes range from +23.3 to -19.56 cal K-1 mol-1 at 20 degrees C.
      Sanguinarine binding to natural DNAs and homo- and heteropolymers of AT is
      characterized by negative enthalpy changes and positive entropy changes, while
      binding to homo- and heteropolymers of GC is reflected by both negative enthalpy
      changes and entropy changes. Possible molecular contributions towards sign and
      magnitude of the thermodynamic parameters and their dependence on ionic strength,
      base composition and sequences, are discussed.

PMID- 8867336
TI  - Differential scanning calorimetric studies on the effect of ammonium and
      tetraalkylammonium halides on the stability of lysozyme.
AB  - The thermal denaturation of lysozyme was studied at pH 2.50 and 6.00 in aqueous
      solutions of ammonium (NH4Cl and NH4Br) and tetraalkylammonium halides (Me4NCl,
      Me4NBr, Et4NBr, Pr4NBr, Bu4NBr) using high-sensitivity differential scanning
      calorimetry. The transition temperature, heat capacity, enthalpy, entropy and
      free energy of denaturation have been determined by a least-squares fit of the
      excess heat capacity data to the two-state model. Ammonium and tetraalkylammonium
      halides (except Me4NCl and NH4Cl at high concentrations at pH 6.00) are found to
      destabilize lysozyme and the destabilization increases with increasing
      concentration and alkyl chain length. However, NH4Cl and Me4NCl act as
      stabilizers at high concentrations at pH 6.00. Results are discussed in terms of
      electrostatic and hydrophobic interactions. The stabilization of lysozyme by
      NH4Cl and Me4NCl can be attributed to the charge on the quaternary nitrogen atom
      while destabilization in tetraalkylammonium halides solution is due to the
      interaction between hydrophobic molecules of the medium and the hydrophobic parts
      of the protein.

PMID- 8867337
TI  - A graph-topological approach to recognition of pattern and similarity in RNA
      secondary structures.
AB  - Secondary and tertiary RNA structures play an important role in many biological
      processes. Therefore the necessity arises to find similar higher-order structures
      for different but functionally homologous RNA sequences. We propose here a graph
      topological approach to the problem, which shows two main features: simplified
      graph representation which allows the recognition of similarity of RNA secondary
      structures with the same branching look despite minor differences. This allows
      comparison among foldings from different sequences, and "pruning" of the
      secondary structures not shared by all the sequences since the early stages of
      the search. (b) The graph representation is encoded by the Randic topological
      index, and the search for the folding similarity is reduced to checking the
      identity of single numbers. These characteristics make this approach
      significantly different, less depending on empirical criteria, and less
      computationally heavy then previous methods, where the folding consensus has been
      measured by an alignment procedure or correlation of strings representing the
      secondary structures. Some U2 snRNA and viroid sequences are studied by this
      approach, which is imbedded in our previous search method based on genetic
      algorithms.

PMID- 8867338
TI  - A study of melittin, motilin and galanin in reversed micellar environments, using
      circular dichroism spectroscopy.
AB  - Circular dichroism spectroscopy has been used to study the behaviour of the
      cytolytic peptide melittin, the intestinal peptide hormone motilin (porcine) and
      the neuropeptide galanin (porcine) in various reversed micellar systems. The
      micellar systems used contained sodium dodecyl sulphate, bis(2-ethylhexyl)
      sulfosuccinate, n-dodecyltrimethylammonium chloride or polyoxyethylene(7) lauryl
      ether. Various structural changes of the peptides, induced either by varying the
      water content or the surface charge of the reversed micelles, could be monitored.
      Melittin has in all micellar systems a large amount of alpha-helix, and is almost
      unaffected by both water content and the surface charge of the reversed micelles.
      Motilin on the other hand attains an alpha-helical structure at low water content
      only. The surface charges seem to be of importance for the association between
      motilin and the hydrated reversed micellar surface. Galanin has the most
      complicated behaviour with a large dependence on surface charge and with a water
      content dependence which varies with the surfactant used. Stabilization of alpha
      helical secondary structures was only seen in negatively charged reversed
      micelles. These observations indicate a specific interaction between galanin and
      surfactant, probably of electrostatic nature.

PMID- 8867339
TI  - Estimation of average depth of penetration of melanotropins in
      dimyristoylphosphatidylglycerol vesicles.
AB  - The interaction of alpha-melanocyte stimulating hormone (alpha-MSH) and its
      analogs [Nle4,D-Phe7]-alpha-MSH (MSH-I) and [Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4
      10) (MSH-II) with vesicles of dimyristoylphosphatidylglycerol (DMPG) was studied
      by steady-state fluorescence spectroscopy. The association constants for the
      interaction were obtained from binding isotherms. Electrostatic effects on the
      interaction were taken into account through calculation of Gouy-Chapman
      potentials. The quenching of fluorescence of the peptides by acrylamide and
      nitroxide labeled lipids demonstrated that insertion of the peptides into the
      lipid phase of the vesicles causes the changes in the hormone's fluorescence in
      the presence of DMPG. The parallax method was employed for the estimation of an
      average depth of penetration of the peptides in the DMPG vesicles. It was found
      that the Trp residue in alpha-MSH and in MSH-II is positioned around the carbons
      6 and 8 of the aliphatic chain. The analog MSH-I goes deeper into the bilayer
      compared to the others peptides, and the Trp residue locates between carbons 10
      and 11 of the acyl chain. The average depth of penetration shows correlation with
      the number of lipid molecules that interact with one molecule of peptide. There
      is no direct correlation between the association constants for the lipid-peptide
      interactions and the depth of penetration of the hormone.

PMID- 8867340
TI  - Construction and performance of a photobleaching recovery apparatus with
      microsecond time resolution.
AB  - A fluorescence recovery after photobleaching (FRAP) apparatus was constructed to
      measure sub-millisecond fluorescence recovery processes in living cells. The
      photobleaching pulse and probe beams were generated by modulating the intensity
      of a continuous wave Argon laser (4 W) by two acousto-optic modulators in series.
      The maximum intensity modulation was > 10(6):1 with a rise time of < 1
      microsecond and a minimum pulse width of 6 microseconds. Fluorescence was
      detected by a photomultiplier, amplified by a transimpedance amplifier, and
      digitized at 1 MHz. During the photobleaching pulse, the photomultiplier gain was
      reduced by ca. 1500-fold by switching the second dynode voltage ca. 100 V
      negative with respect to the cathode voltage by computer control of two
      bidirectional Mosfet optoisolators. The switching circuit produced a
      optoisolators. The switching circuit produced a transient anode current (t
      approximately 15 microseconds) which was subtracted for measurement of recoveries
      of < 50-100 microseconds. The apparatus was coupled to an inverted microscope for
      measurement of fluorescence by epi-illumination or total internal reflection.
      Instrument performance was evaluated by measurement of the rapid fluorescence
      recoveries of fluorescein and fluorescein-dextrans in solutions and living cells.

PMID- 8867341
TI  - [Quality assurance in surgery--more than documentation of postoperative
      complications].
AB  - This review discusses several aspects of surgical quality assurance: 1. The
      surgical audit to collect data and analyze postoperative complications. 2.
      Quality assurance by measurement of patients' postoperative long-term outcome. 3.
      The elaboration of therapeutical guidelines. 4. Measurement of costs and benefit
      of the surgical intervention including patients' postoperative quality of life.
      5. Quality assurance of clinical trials and medical publications. It is
      demonstrated that the regular documentation of postoperative complications and an
      internal data analysis improve the results, dependent on the quality of the data
      which is best guaranteed by a neutral observer. The late results after operation
      are mainly influenced by the quality of the surgeon, as prove recurrence rates
      after hernia repair ranging between 0 and 10% using identical operation
      techniques, or locoregional recurrences of 30-60% after abdominal perineal
      resection of the rectum. The elaboration of therapeutical guidelines may be
      helpful for the evaluation of the benefit of the intervention and for the
      prevention of unnecessary operations as has been demonstrated for the treatment
      of symptomatic and asymptomatic carotid artery stenoses. Qualified clinical
      studies performed according to the GCP rules with biometrical planning, clear cut
      definition of the purpose of the study and listing of inclusion and exclusion
      criteria are the prerequisites of substantiated therapeutical guidelines. Under
      increasing economic pressure not only the benefit, but also the costs of
      treatment are of major importance, the evaluation of the cost effectiveness ratio
      by measuring the cost per quality adjusted year of life saved will become
      essential for future therapeutical recommendations.

PMID- 8867342
TI  - [After-care of gastrointestinal malignancies--an evaluation of costs and
      benefits].
AB  - AIM OF THE STUDY: To determine the costs and benefit of standardized follow-up
      programs after surgical therapy of gastrointestinal malignancies. METHODS:
      Retrospective analysis of the results and the costs of regular outpatient follow
      up examinations after radical resection of colorectal (n = 552), gastric (n =
      180), and esophageal carcinoma (n = 160). RESULTS: The diagnostic efficiency of
      regular follow-up concerning the diagnosis of asymptomatic tumor recurrences was
      9% in esophageal, 10% in gastric, and 15% in colorectal carcinoma. The average
      follow-up costs for each asymptomatic recurrence were about 10.000 DM. R0
      resection of asymptomatic recurrences or metachronous tumors was performed in
      none of the patients with esophageal and gastric carcinomas and in 22 patients
      with colorectal carcinomas (4% of all patients with colorectal carcinomas). In
      contrast to the low therapeutic efficiency in tumor recurrences, the therapeutic
      efficiency with regard to the treatment of postoperative nonmalignant functional
      disorders was significantly higher (esophageal carcinoma: 63%, gastric carcinoma:
      40%, colorectal carcinoma: 24% of the follow-up examinations). CONCLUSIONS: In
      order to examine, whether the cost-benefit-relation of regular follow-up programs
      can be increased by some quantitative and qualitative modifications of the
      programs, controlled economic studies are required.

PMID- 8867343
TI  - [Prognostic factors in local recurrence rate after surgical therapy of rectal
      carcinomas].
AB  - From January 01, 1985 to December 31, 1993 515 patients with primary rectal
      cancer underwent operative treatment at the hospital of general and abdominal
      surgery of the university of Mainz. In 294 patients with conventional surgical
      treatment and R0-resection of the tumor we investigated the influence of tumor-,
      patient- and therapeutic factors on local tumor recurrence. At a univariate
      analysis the following factors were significant: UICC-staging (p = 0.001), pT
      classification (p = 0.001), pN-classification (p = 0.013) and localisation of the
      tumor (p = 0.013). These results could be verified for the pT-classification and
      pN-classification in a multivariate analysis. The significant influence of
      operative treatment (p = 0.034), blood transfusion (p = 0.018) and preoperative
      raised CEA (p = 0.026) depended on significant differences of UICC - staging and
      tumor - localisation of the different groups. Grading, sex and age had no
      influence. Inspite of a shift of local resurrence from 13% to 50% (0% to 42.9%
      for resections, respectively 6.7% to 55.4% for exstirpations) we could not find a
      significant influence of the surgeon. This fact depended on the dividing of a
      small number of cases on a lot of surgeons. In our opinion the influence of the
      surgeon or of different hospitals on local recurrence should be investigated in
      further studies.

PMID- 8867344
TI  - [Local excision of rectal carcinoma].
AB  - From January 1985 till December 1994 109 patients with rectal carcinoma were
      treated by local excision, in 36 patients a radical operation was performed
      afterwards. In the assessment of tumor infiltration endosonography was superior
      to rectal-digital examination. In 34 patients with local excised "low risk" T1
      carcinomas and tumor free margins no local recurrence was observed. Two of ten
      patients with local excised "low risk" T1-carcinoma and no adequate margin of
      healthy tissue developed a local recurrence. Regarding our results the local
      excision of "low risk" T1-carcinomas seems justified, if final histological
      workup reveals an adequate margin of healthy tissue.

PMID- 8867345
TI  - [Surgical treatment of diverticulitis of the large intestine--a plea for early
      elective resection].
AB  - PURPOSE: Diverticulitis of the colon is observed more and more frequently in
      highly developed countries. The spontaneous course of the disease is not
      predictably; an exact definition of risk factors for perforated diverticulitis is
      missing. Therefore the decision for the conservative therapy or for an early
      elective resection is subject of a controversial discussion. The results of an
      offensive surgical concept, aiming at an early elective resection for definite
      therapy of diverticulitis have been analysed in a retrospective study. RESULTS:
      From 1980-1995 337 patients were operated due to diverticular disease (rate of
      resection: 98.8%). In spite of the increase of cases with severe complicated
      diverticulitis from 36.2% (1980-1985) to 45.8% (1991-1995; p = 0.05) the
      incidence of protective colostomies decreased from 18.8% in the first six years
      to 0.6% (n = 1) in the last 4 1/2 years (p < 0.001). After elective resection
      general complications occurred in 30.1% (n = 101), local complications in 17.0%
      (n = 57). The clinical anastomotic leakage rate was 2.1% (n = 7). During the
      study the morbidity rate decreased significantly (p < 0.005). Especially the
      incidence of nosocomial infections was reduced from 37.7% (1980-1985) to 14.8%
      (1991-1995); severe local complications (anastomotic leakage, bowel obstruction,
      peritonitis, hemorrhage, abscess) were reduced from 10.1% (1980-1985) to 3.2%
      (1991-1995). The mortality rate was 1.2% (n = 4). CONCLUSION: By consistent early
      elective resection of diverticulitis together with a standardized surgical
      management a definitive treatment of diverticulitis with a high and safe standard
      is possible. Already after the first severe attack of the disease, which leads to
      hospitalization, the early elective resection allows the definite cure for
      diverticular disease analogous to cholecystectomy or appendectomy, avoiding the
      life threatening complications.

PMID- 8867346
TI  - [Esophageal diverticulum--perioperative risks and long-term follow-up].
AB  - Between 1985 and 1994 36 patients with Zenker's diverticulum were operatively
      treated by excision of diverticulum and cricopharyngeal myotomy at the University
      department of Surgery, Mainz. The complication rate was 25% (9 of 36 patients),
      in 2 cases a suture insufficiency was detectable. Long-term results are based on
      follow-up studies of 32 patients. The average follow-up interval was 59 (10-101)
      months, 20 patients (56%) underwent radiological examinations or endoscopy. 29 of
      32 patients were totally symptomfree concerning the esophagus. After an average
      follow-up of almost 5 years there was no symptomatic recurrence. In 1 of 20
      radiologically or endoscopically examined patients an asymptomatic recurrence
      could be detected. These results show that excision of the diverticulum in
      combination with a cricopharyngeal myotomy is an effective method with low risk
      for the long-term removal of pharyngoesophageal diverticulum.

PMID- 8867347
TI  - [Change in the risk of gastroduodenal ulcer hemorrhage--preventive or elective
      operation?].
AB  - Prophylactic (early elective) surgery of bleeding gastroduodenal ulcers is
      performed to avoid rebleeding with a supposed high risk. Because early elective
      surgery was burdened with high risk for complications and because surgery for
      rebleeding ulcers had no higher risk, we left these procedures and performed
      repeated endoscopic treatment of these patients instead. A retrospective analysis
      should clarify, whether the modified treatment since 1/90 changed the risk of
      bleeding gastroduodenal ulcers. Patients of other hospitals, who were assigned
      after unsuccessful attempts of conservative treatment were analysed separately
      from patients of the emergency ward of our department. In the second period
      patients from other hospitals were in worse condition, they had more concomitant
      diseases and more intense bleedings than in the first period. In our opinion this
      could be attributed to carrying too far conservative treatment. The frequency of
      operations decreased only little in this group, whereas the complication rate and
      the mortality increased slightly. With the abandonment of early elective surgery
      in patients of our emergency ward, we reached a decrease of the operative
      frequency of more than 30%, a decrease of complications from 27.6% to 10.0% and
      of mortality from 10.3% to 0%. Over-all mortality was reduced from 9.8% to 4.7%.

PMID- 8867348
TI  - [Talc pleurodesis in recurrent malignant pleural effusion--a prospective follow
      up study].
AB  - Talc pleurodesis was performed in a prospective trial in 38 patients with
      recurrent malignant pleural effusion. After insertion of a chest tube a slurry
      containing 8g of iodined talcum, 0.5 ml of 1% xylocain/kg/body weight, and 80 ml
      of 0.9% NaCl was administered and suction drainage was performed. The chest tube
      could be removed after 4 +/- 1.7 days. A successful therapy could be achieved in
      33/38 patients (86.8%). 2 patients (5.3%) suffered from recurrent pleural
      effusion which only in 1 case had to be drained. 3 patients died within the first
      month after talc pleurodesis due to an advanced cancer stage. Complications did
      not come to evidence in any case.

PMID- 8867349
TI  - [Infrarenal abdominal aortic aneurysm--indications for surgery and survival].
AB  - PURPOSE: Elective operation is an established therapy in the management of
      infrarenal aortic aneurysms. Surgery has an acceptable low risk in the presence
      of experienced surgeons and anaesthetists. Indication for surgery nevertheless
      remains a difficult problem, because diagnostic procedures and evaluation of
      different criteria do not exactly predict the likelihood of rupture. Indication
      for surgery is moreover dependent on operative mortality and late survival. This
      study analyses early and late results associated with the repair of abdominal
      aortic aneurysms in our institution in Hamburg and comments on indication for
      elective surgery. METHODS: Life-Table analysis was used to determine survival
      rate. Calculation of expected prevalence of abdominal aortic aneurysms in the
      Hamburg population was based on demographic statistics and results in the
      literature. RESULTS: Between January 1981 and April 1995 1242 patients underwent
      abdominal aortic aneurysm repair, 1018 electively, 224 for ruptured aneurysm.
      Operative mortality was 4% and 50% respectively. The survival rate after elective
      operation was 64% at 5, 43% at 10 and 35.4% at 14 years, while after emergency
      surgery for ruptured aneurysm it was 40% at 5, 31.9% at 10 and 29.8% at 14 years.
      The survival rate of survivors after repair for ruptured aneurysms is similar to
      that after elective surgery. Over a 13 years period the rate of ruptured
      aneurysms did not decrease. Comparison of surgical data and calculated prevalence
      data show that a three times higher operative activity is requested to repair all
      occurring abdominal aortic aneurysms larger than 5 cm in diameter. CONCLUSIONS:
      In order to reduce the still high mortality associated with aneurysm rupture
      there is still a need for more prophylactic surgery.

PMID- 8867350
TI  - [Preliminary results of a prospective randomized study vascular replacement above
      the knee].
AB  - In case of insufficient or missing greater saphenal vein or if the saphenal vein
      might be of important use for future bypass grafts, the question arises which
      alternative bypass material is the more appropriate choice. A literature review
      to that topic produced only unsatisfactory results. In a prospective randomized
      controlled clinical study (n = 250 patients) we compare the patency rates of
      either PTFE or Dacron as bypass material for femoropopliteal P-I-Bypass in
      chronic arterial occlusive disease. A preliminary evaluation of n = 103 patients
      (PTFE n = 52; Dacron n = 51) reveals an operative and immediate mortality rate of
      0% and a loss of limb rate of 3.9% (PTFE) and 3.8% (Dacron). The secondary
      cumulative patency rate after 540 days of observation is 79.6% (PTFE) and 87.1%
      (Dacron). We so far find no statistically significant difference between both
      graft materials.

PMID- 8867351
TI  - [Clinical results of extremity perfusion in malignant melanoma].
AB  - Side effects and results of isolated hyperthermic extremity perfusion in
      malignant melanoma at the University of Cologne were reviewed: Severe local and
      systemic side effects (WHO grade III, IV) occurred in 3%, 5-year survival rates
      were 100% in TNM stage I patients (n = 27), 88.7% in TNM stage II patients (n =
      123), 46.4% in TNM stage III patients (n = 169) and 36.3% in TNM stage IV
      patients (n = 22). 5-year recurrence free survival rates were 100% in TNM stage
      I, 73.4% in TNM stage II, 20.8% in TNM stage III and in TNM stage IV 9.1%.
      Indication for extremity perfusion remains locoregional recurrent disease.

PMID- 8867352
TI  - [Ambulatory artificial nutrition: 15 years experiences at the Cologne University
      Surgical Clinic].
AB  - Beetween 1979 and 1994 629 respectively 223 patients were treated by home enteral
      and parenteral nutrition. The duration of the treatment on average was 361 days
      in case of enteral and 346 days for home parenteral nutrition, in special cases
      however up to 15 years. In enteral nutrition there were no metabolic
      complications and only minor technical problems. Catheter related problems
      represented the most challenging complications in parenteral feeding. 12 out of
      14 patients treated more than 1 year with home parenteral nutrition because of
      non-cancerous disease died from recurrent pulmonary embolism or catheter-related
      septicemia.

PMID- 8867353
TI  - [History of autologous blood transfusion in the 19th century].
AB  - Autologous blood transfusion in animal experiments was performed already in the
      first half of the 19th century. These experiments, however, were not conducted to
      explore the feasibility of autologous blood transfusion in man, but provided only
      the experimental design for physiological investigations on the defibrination of
      blood. Blood withdrawn from the animals by phlebotomy in these experiments was
      retransfused either with or without defibrination. The idea of retransfusing the
      patient's own blood was mentioned for the first time by Eulenburg and Landois,
      when in 1866 they proposed to treat gas poisonings with a type of exchange
      transfusion (transfusion with simultaneous depletory bleeding). They suggested
      that the blood that would be withdrawn could be retransfused after the poisonous
      gases had been eliminated. The first who demonstrably considered the possibility
      of autologous blood transfusion in operative medicine was the Halle surgeon
      Richard von Volkmann in 1868. The first originally sourced autologous blood
      transfusion, however, was performed by the Kiel surgeon Friedrich von Esmarch
      who, in a case of exarticulation of the thigh at the hip joint, collected the
      blood that had been shed during the operation in a washbowl, defibrinated it, and
      reinjected it into the severed femoral vein. However, despite some further cases
      of autologous blood transfusion performed for various indications and in
      different countries, the method was unable to gain a foothold in the treatment of
      acute blood loss, and fell into oblivion until the Leipzig gynaecologist Johannes
      Thies revived interest in it in 1914. The authors surmise that the advantages of
      autologous blood transfusion had not been recognised in the 19th century.

PMID- 8867354
TI  - [The new graduate education ruling for neurology].

PMID- 8867355
TI  - [Changes in regional and local brain circulation in patients with subarachnoid
      hemorrhage due to ruptured aneurysm].
AB  - It is well known that cerebral blood flow (CBF) is altered corresponding to the
      severity of the subarachnoid hemorrhage (SAH) in different extents. The extent of
      CBF reduction and its regional accentuation is regarded as a pathophysiological
      correlation of clinical conditions. Therefore, we agree that CBF of patients in
      grade IV+V (Hunt and Hess) are clearly lower than in grade I+II. There are quite
      different results in grade III. Disturbance of consciousness and/or neurological
      deficits, as described in the definition of grade III, can be a consequence of
      different kinds of CBF changes. 45 Xe-CT studies were performed on 19 patients
      (mean age 44 +/- 14 years) after SAH. 8 patients were of grade I+II, 7 of grade
      III, and 4 patients of grade IV+V. The studies were performed preoperatively, at
      a time of clinical change, and before discharge. The evaluation of flow-maps was
      done by measuring 15 regions per hemisphere. Mean CBF data were evaluated in each
      area. To show the CBF differences between both hemispheres within each group of
      patients, a difference index (%) was calculated. The results demonstrated a mean
      CBF reduction in nearly all regions from grade I+II to grade III up to grade
      IV+V. The mean CBF reduction between grade I+II and grade III was 10% for gray
      and 20% for white matter (p < 0.05). On the other hand the difference index of
      gray matter in grade III with 17% is significantly higher than in grade I+II. For
      the white matter there was no significant side difference. Our findings
      demonstrate a visually evaluable pattern of CBF corresponding to grade I+II,
      grade III, and grade I+V. Intention of this study was to show a correlation
      between clinical conditions of patients after SAH and the CBF changes by the use
      of Xe-CT method.

PMID- 8867356
TI  - Considerations in the prophylactic treatment of transient ischemic attack or
      ischemic stroke in the carotid artery territory.
AB  - This non-randomized study surveys the prophylactic treatment of 154 patients
      after transient ischemic attack or ischemic stroke in the carotid artery
      territory. Clinical presentation and etiologies were compared on the basis of the
      proposed prophylactic treatment. A surgical intervention or a long-lasting
      anticoagulation was restricted to only 30 patients (20%) due especially to the
      gravity of the ischemic cerebral lesions, general deterioration, and the advanced
      age of most of the patients. The purpose is to emphasize the "down-to-earth"
      situation in current medical care of non-selected patients as distinguished from
      the strictly selected patients of randomized studies. More importance should be
      done to open studies which better reflect the daily medical reality.

PMID- 8867357
TI  - [Neuritis of multiple cranial nerves in idiopathic focal pachymeningitis].
AB  - A 76 years old patient suffering from insulin dependent diabetes presents a
      multiple, bilateral and asymmetric cranial neuropathy involving on the left side
      the cranial nerves VIII, IX with a participation of the efferent autonomic fibers
      of the nerves VII and IX (xerostomia) and the nerve XII, and involving on both
      sides the nerves VII and X. Like it is known from literature the nerve XI was
      spared, probably because of the more caudal emergence from the brainstem. The
      disease was preceded by a violent otalgia on the left side which was initially
      interpretated as a malignant external otitis. This affection was associated with
      an inflammatory syndrome that was easily monitored by the blood sedimentation
      rate. The course was favorable but marked by fluctuations of the neurological
      deficits. The MRI shows a pachymeningitis localised at the beginning in the
      medial fossa and on the cerebellar tentorium, later on the left parieto-occipital
      convexity. The diagnosis of a focal idiopathic pachymeningitis was confirmed by
      excluding different other affections like inflammatory, tumoral and infectious
      diseases, by using MRI examinations, CSF analysis and especially meningeal
      biopsy. It is a rare inflammatory disease of unknown origin with potentially
      persistent neurological deficits. We discuss the differential diagnosis and the
      therapeutical possibilities, which consist in a long term immunosuppression with
      corticosteroids and azathioprine.

PMID- 8867358
TI  - Brain irradiation and antioedematous dexamethasone treatment--risk factors for
      herpes simplex encephalitis?
AB  - Herpes simplex encephalitis (HSE) could result from the reactivation of an
      endogenous latent herpes simplex virus (HSV) in sensory ganglia or in brain
      parenchyma. Virus replication and a new lytic virus cycle may be triggered by a
      wide variety of factors. One of these might be irradiation as suggested by
      experimental evidence obtained in mouse trigeminal ganglia. Here we report the
      occurrence of HSE in a 52 years old woman two months after brain irradiation (40
      Gray in 20 fractions) and dexamethasone administration for a metastatic brain
      tumor. HSE has already been observed in a clinical context very similar to that
      reported here, suggesting that brain irradiation together with corticoid therapy
      may, in some rare patients, favour the occurrence of HSV reactivation and HSE.

PMID- 8867359
TI  - Participation of oxygen-free radicals in the oxido-reduction of proteins.
AB  - Recent studies have focused attention on the possible role of active oxygen
      species on protein damage and degradation. The reactions of free radicals on
      biomolecules are important in physiology and pathology. A number of systems that
      generate free radicals catalyze the oxidative modification of proteins in two
      species: protein peroxides, which can consume important antioxidants; and protein
      bound reducing moieties, which can reduce transition metals, and may enhance
      their activity in radical reactions. Protein oxidation also contributes to the
      pool of damaged enzymes and accumulation of abnormal and damaged proteins, which
      increases during aging and in various pathological states, such as
      atherosclerosis, cancer, etc.

PMID- 8867360
TI  - Recovery of congenital facial palsy in patients with hemifacial microsomia
      subjected to sural to facial nerve grafts is enhanced by electric field
      stimulation.
AB  - The effect of electric field stimulation for promoting axonal growth between
      sural to facial nerve grafts in cases of congenital permanent facial palsy
      associated with hemifacial microsomia was studied. For this purpose, a total of
      17 patients with unilateral congenital permanent facial palsy associated with
      hemifacial microsomia were studied pre- and post-operatively. A sural to facial
      nerve graft was performed in all cases and long term postoperative electric field
      stimulation was randomly applied to half of the patients. Although improvement
      occurred in both groups, the results indicated that clinical and
      electrophysiological recovery was significantly better in patients receiving post
      operative electric field stimulation. The results, therefore, suggest that
      electric stimulation of the grafted area induces improvements of facial palsy
      over and above those observed in the non-stimulated patients.

PMID- 8867361
TI  - Treatment of patients with hemophilia A and inhibitors to factor FVIII with
      cimetidine.
AB  - In this study, cimetidine was used to treat patients with hemophilia A and
      inhibitors to factor VIII who presented with acute hemorrhages (Group A) and
      those without hemorrhages (Group B). The dose of cimetidine was 15 mg/kg/day.
      Group A consisted of five patients with inhibitors between 156 and > 10,000
      Bethesda Units (BU), all with serious hemorrhagic problems. The control of
      hemorrhaging was effective in 100% of these patients, although inhibitor levels
      remained high (25-380 BU). Group B consisted of seven patients who did not have
      hemorrhages, whose inhibitor levels were 41-358 BU. Five of these patients no
      longer had anamnestic responses to Factor VIII after several months of treatment
      with cimetidine. No difference in the response to cimetidine was seen between HIV
      positive and HIV negative patients. The results suggest that cimetidine is useful
      to suppress inhibitors to Factor VIII in patients with hemophilia A.

PMID- 8867362
TI  - Undiagnosed hypercholesterolemia: a serious health challenge. The Mexico City
      Diabetes Study.
AB  - In this report we present the results of a population based survey designed to
      characterize the prevalence of hypercholesterolemia (HCL: total cholesterol > or
      = 240 mg/dl) in a low income urban area of Mexico City (The Mexico City Diabetes
      Study). In an area of 15,532 inhabitants, 3505 (22.57%) were found to be study
      eligible (all 35-64 year-old men and nonpregnant women residing in the area
      permanently). A home interview was obtained in 2813 (80.26%) subjects. A physical
      exam and oral glucose tolerance test was performed on 2282 (81.2% of the
      individuals that gave the interview and 65.1% of all study eligibles, 941 men and
      1341 women). The crude prevalence of HCL for men in this group was 12.3% and for
      women 12.5%. Severe HCL (total cholesterol > or = 260 mg/dl) was found in 6.6% of
      men and 6.5% of women. In the older age group (55-64 years) prevalence in women
      reached 21.1%. Of the individuals with HCL this abnormality was previously
      diagnosed in only 15.9% of men and in 7.8% of women. Despite having been
      diagnosed, the abnormality remained untreated in all cases. HCL was associated
      with higher mean systolic blood pressure (in women), higher mean diastolic blood
      pressure (in men) and higher mean fasting and 2 h post-glucose load glycemia as
      well as post-challenge insulinemia in both sexes. Mean TG was found high in both
      groups (with and without HCL), but in subjects with HCL the values were
      significantly higher. We conclude that HCL is very common in this population. The
      majority of the cases remained undiagnosed and of the small fraction of subjects
      that have been diagnosed, virtually none is under medical care. It is necessary
      to design and implement a national program to reduce the impact of this serious
      health problem.

PMID- 8867363
TI  - Cytomegalovirus infection in children: frequency, anatomopathologic
      characteristics and underlying risk factors in 1618 autopsies.
AB  - The aim of this study was to determine the frequency of cytomegalovirus (CMV)
      infection in children with postmortem study. The records of 1618 autopsies
      performed during 1980-1989 at the Hospital Infantil de Mexico Federico Gomez were
      reviewed. Characteristic cytomegalovirus inclusion bodies were identified, in one
      or several organs, in 47 cases (2.9% of the autopsies). None of these cases was
      cultured for viruses prior to or at the time of autopsy. Of the 47 cases, 24
      (51%) with CMV were younger than 3 months and 38 cases (80%) younger than 12
      months of age. In eight cases, the infection was judged as generalized and
      considered the cause of death. Two of these patients were premature and the
      infection was most probably intrauterine. The risk factor most frequently
      identified was secondary immunosuppression. The lung was the most common affected
      organ, followed by kidney, adrenals, pancreas, liver, brain and salivary glands.
      In seven cases the inclusion bodies were seen in the brain and in three others
      periventricular calcifications without inclusion bodies were observed. Although
      not a rarity in Mexico, CMV infection is not often suspected. Additional studies
      are needed in order to determine the prevalence of CMV infection in Mexico.

PMID- 8867364
TI  - Modified clearing technique to identify lymph node metastases in post-irradiated
      surgical specimens from rectal adenocarcinoma.
AB  - The aim of this study is to describe a modification of the original method of
      clearing lymph nodes in specimens from rectal adenocarcinoma and its yield in
      comparison to a control group whose specimens were studied by a manual technique.
      There were 32 consecutive patients with locally advanced rectal adenocarcinoma.
      All patients received preoperative radiation therapy (PRT) at doses of 45 Gy,
      concomitant with 5-fluorouracil at the doses of 450 mg/m2 IV bolus, days 1-5 and
      28-33 of PRT; 4-8 weeks later radical surgery with a curative intent was
      performed. Twenty two specimens were studied by a manual technique consisting of
      fixation in 10% formalin. Ten specimens were studied with the modified clearing
      technique consisting of administration through the inferior mesenteric artery of
      methylene blue; fixation with 10% formalin plus 0.01% of methylene blue; clearing
      the fat with a sequence of 95% alcohol-100% acetone-100% xylene. In the 32
      specimens, 413 lymph nodes were found. Using the manual technique 104 lymph nodes
      were found (average 4.7 lymph nodes per specimen); 309 lymph nodes by the
      modified clearing technique (average 30.9 lymph nodes per specimen), (p <
      0.0001). Using the manual technique 23 out of 104 lymph nodes (22%) contained
      metastases. All metastatic lymph nodes measured > 5 mm; 18 out of 23 metastatic
      lymph nodes were located on the perirectal area (level 2); and five were located
      in the root of the inferior mesenteric artery (level 5). Using the modified
      clearing technique 278 out of 309 (89%) lymph nodes measured < 5 mm; 15 out of
      309 (4.8%) lymph nodes contained metastases; 9 out of 15 (60%) measured > 5 mm
      and were located on levels 2 and 5; and six, located on level 5, measured < 5 mm.
      The modified clearing technique is a quick, easy and reproducible method for
      identifying lymph nodes in post-irradiated surgical specimens. In comparison to
      the traditional manual method of searching for lymph nodes, it improves in the
      detection of small lymph nodes (< 5 mm), allowing better staging in patients with
      rectal adenocarcinoma.

PMID- 8867365
TI  - Electrochemical fixation techniques. I. Electrochemical fixation of human brain.
AB  - An electrochemical brain fixation procedure (EBFP) to treat brains excised from
      human cadavers is described thoroughly. It is as precise as any other similar
      method currently available. However, it takes only as much as 36 h to completion
      instead of the much longer lapses required by immersion in formaldehyde. Actions
      were taken to secure that it is not a source of artifacts of any kind, neither
      neurons nor glia or blood vessels. It is, therefore, amenable to be used as a
      valuable research and teaching tool. Other advantages are that it does not pose
      any health hazard, is money- and time-saving, and cuts down on equipment and
      facilities.

PMID- 8867367
TI  - Changes in lysosomal enzyme activities in pre-ovulatory follicles and endometrium
      of PMSG superovulated rats.
AB  - Large superovulatory doses of gonadotrophins result in reduced fertility in
      laboratory and large domestic animals and it has been postulated that some of the
      superovulated oocytes are derived from abnormal follicles which would not ovulate
      under normal physiological stimuli. Follicular growth, follicular maturation and
      atresia, ovulation and the nidation of the fertilized oocyte require intense
      tissue remodelation which can be accomplished only through the action of
      hydrolytic enzymes. We have studied the activities and sub-cellular distribution
      of three lysosomal enzymes (acid phosphatase, N-acetyl-beta-D-glucosaminidase and
      beta-glucuronidase) in the follicular fluid, granulosa and theca cells of
      preovulatory follicles and in the endometrial tissue of immature Wistar rats
      injected with 4 (control) or 40 (superovulated) IU of pregnant mare serum
      gonadotrophin (PMSG). Enzyme activities were from four to ten times higher in
      theca than in granulosa cells. This difference was particularly important in the
      case of beta-glucuronidase. Large preovulatory follicles tended to have higher
      activities of lysosomal enzymes in the free fraction of all the compartments
      studied. This difference was remarkable in theca cells where free enzymes would
      be required to help ovulation. Forty IU of PMSG induced higher activities of acid
      phosphatase in theca and granulosa cells than 4 IU, but in endometrial tissue
      this latter dose of PMSG was more efficient to induce higher activities of this
      enzyme. The endometrial bound fraction of N-acetyl-beta-D-glucosaminidase was
      almost three times higher than the free activity. This behavior was also observed
      in endometrial beta-glucuronidase but only in the control rats. The results
      observed in follicular fluid were less homogeneous. The activities of
      glucosaminidase and acid phosphatase were two to three times higher in rats
      overstimulated with 40 IU of PMSG than in the control rats, whereas the
      activities of beta-glucuronidase were lower in the superovulated rats. Our
      results suggest that alterations in the process of tissue remodeling required for
      ovulation of mature, normal oocytes and for nidation of the fertilized ovum may
      be important factors to explain pregnancy failure in the PMSG superovulated
      female.

PMID- 8867366
TI  - Inhibition of three alphaherpesviruses (herpes simplex 1 and 2 and pseudorabies
      virus) by heparin, heparan and other sulfated polyelectrolytes.
AB  - The first step of the herpes virus infection is the attachment to heparan sulfate
      molecules on the cellular membrane. In order to improve the characterization of
      this phenomenon, we compared the inhibitory effect of six sulfated
      polyelectrolytes (PE): heparin, heparan, low molecular weight heparin,
      chondroitin, dextran and protamine on plaque formation by pseudorabies virus
      (PRV) were compared. The PE with the highest antiherpetic effect was heparin,
      followed by dextran sulfate. Heparan sulfate, which has been proposed as the
      initial receptor of herpes virus on the cell surface showed an effect 100-fold
      lower than heparin. Comparative inhibition curves of heparin and heparan sulfate
      against three herpes viruses: herpes simplex virus 1 (HSV-1), HSV 2 and PRV
      showed similar kinetics of inhibition of plaque formation, suggesting these
      viruses could share similar cell adsorption mechanisms.

PMID- 8867368
TI  - Storage histiocytes and hemophagocytosis: a common finding in the bone marrow of
      patients with active systemic lupus erythematosus.
AB  - We report the frequency of the finding of storage and hemophagocytic histiocytes
      in the bone marrow of patients with systemic lupus erythematosus with one or more
      hemocytopenias. The study was performed on bone marrows of ten patients with
      systemic lupus erythematosus during an episode of hemocytopenia. Four patients
      were not receiving any treatment and six had been taking oral prednisone (3.5 +/-
      1.5 mg/day) for the previous 6 months. Hemocytopenias found were lymphocytopenia
      in five, thrombocytopenia in three, and neutropenia and anemia in two each. The
      bone marrow had variable cell content; megakaryocytes, the myeloid:erythroid
      ratio, as well as lymphocyte, plasma cell, and reticular cell contents were
      usually increased. Seven bone marrow samples showed storage histiocytes (sea-blue
      histiocytes and other histiocytes that contained unidentified intracytoplasmic
      material). These same samples revealed histiocytes phagocytosing erythoblasts,
      erythrocytes, polymorphonuclear neutrophils, lymphocytes or platelets. The
      presence of these histiocytes in all seven patients was related to a decrease in
      serum complement and with lupus disease activity as measured with the SLEDAI
      index (mean +/- SD = 2.1 +/- 1.5). The SLEDAI score of the remaining three
      patients, who had no histiocytes in their bone marrow, was 0, 0, and 1,
      respectively. The present study reveals that the bone marrow in patients with
      systemic lupus erythematosus and peripheral hemocytopenia contains storage and
      hemophagocytic histiocytes and the significance of these cells is discussed.

PMID- 8867369
TI  - Behavior of long-term dantrolene sodium-treated rat skeletal muscles.
      Histochemical and electromechanical aspects.
AB  - Histochemical and electrochemical studies were carried out on skeletal rat
      muscles treated with dantrolene sodium (DS) for 60 days. Histochemical
      experiments revealed a conversion from fast twitch (type II) to slow twitch (type
      I) fibers for soleus (S), gastrocnemius (GM),a dn extensor digitorum longus (EDL)
      muscles. However, a significant decrease of muscle contractility was not observed
      in these chronically treated rat muscles in opposition to both those directly
      exposed in vitro as the muscles obtained from only 1-h DS-treated animals.

PMID- 8867370
TI  - Detection of immunoglobulins on bacterial surface by laser flow cytometry:
      analysis between Haemophilus influenzae type b and Vibrio cholerae O1 of healthy
      mother-full term newborn sera.
AB  - The identification of human IgG immunoglobulins on the surface of Vibrio cholerae
      O1, and Haemophilus influenzae type b microorganisms was assessed via a flow
      cytometric technique. A group of 31 healthy mother-full term newborn duo sera
      from a non-endemic cholera area was assayed. The sera of mothers and full-term
      newborns against both microorganisms were compared. The mean fluorescent
      intensity of the samples was not different at the 0.05 significance level by
      paired t-test. On the other hand, the immunoglobulins of newborn and mothers for
      V. cholerae O1 was notably lower when compared with H. influenzae type b
      microorganisms (p < 0.05 by paired t-test, t = -5.570 for mothers' sera, and t = 
      7.496 for the sera of the newborns). These data provide circumstantial evidence
      that LFC technique would be useful on bacteria-related serology.

PMID- 8867371
TI  - Pigment cholelithiasis induced by vitamin A and its prevention by butylated
      hydroxytoluene.
AB  - We previously reported on the induction by vitamin A of gallstones, rich in
      calcium and phosphate, in hamsters. On the other hand, it has been reported that
      the phenolic antioxidant butylated hydroxytoluene (BHT) potentiates the
      hepatotoxicity of vitamin A. In the present work we have tested the effect of BHT
      on the lithogenicity of vitamin A and on bile composition. The urinary excretion
      of calcium and phosphate was determined to assess a possible asymptomatic bone
      resorption due to vitamin A toxicity, and/or an effect of BHT on the homeostasis
      of calcium and phosphate. Three groups of 18 male hamsters were fed with the
      following diets for 70 days: Group 1, Purina Nutricubes (DB); Group 2, DB +
      25,000 IU% retinol acetate (DL); Group 3, DL + 500 mg% BHT. Vitamin A (Group 2)
      induced gallstones in 78% of the animals, increased bile flow and biliary
      phosphate and calcium concentrations, and reduced those of bile salt, cholesterol
      and phospholipid. BHT (Group 3) reduced gallstone frequency to 5.5%, and
      decreased biliary phosphate, calcium and lipids toward more normal
      concentrations. Vitamin A alone or with BHT did not significantly affect food
      intake or urinary excretion of calcium and phosphate.

PMID- 8867372
TI  - Vascular smooth muscle cells cultured on elastin membranes.
AB  - Smooth muscle cells from thoracic aortas of 12-week-old rats were cultured on
      elastin membranes for up to 21 days. The cell cultures were examined using light
      microscopy, transmission and scanning electron microscopy. The contractile
      phenotype characteristic for resident arterial wall muscle cell changed to the
      synthetic phenotype. In the synthetic state, the muscle cells contain few
      filaments, but a substantial amount of organelles are involved with synthesis.
      The cells grown on elastin substrates showed a multilayered pattern with the
      formation of nodules. Cell degeneration was present from day eight and increased
      with time. At the end of the experiment, the center of the multilayered areas
      showed degenerative changes with numerous foam cells of smooth muscle origin,
      areas of necrosis and a considerable amount of calcium deposit. Our experimental
      model would be valuable in the investigation of the pathological changes
      associated with smooth muscle cell proliferation in vessels.

PMID- 8867373
TI  - Clomipramine modifies fluctuations of forced swimming immobility in different
      phases of the rat estrous cycle.
AB  - Many symptoms that define the premenstrual syndrome (PMS) are present in
      depressive states. The fact that there are not adequate animal models to study
      the PMS may explain the lack of knowledge about its etiology. An alternative
      might be the use of animal models which are useful to study depression, such as
      the forced swimming test. Eighteen female rats were subjected to the forced
      swimming test once a week for six consecutive weeks. An increase of immobility
      was observed during diestrus as compared to estrus. On the other hand, some
      premenstrual symptoms have been suggested to be caused by the influence of
      gonadal hormones on the activity of central serotonergic systems. Thus, the
      effects of clomipramine were further studied. The drug reduced rat immobility
      during diestrus, so that the differences between the two estrous cycle phases
      disappeared. We conclude that the use of the forced swimming test might be a
      helpful model in the study of PMS.

PMID- 8867374
TI  - Molecular diagnosis of Huntington's disease in Mexican patients by polymerase
      chain reaction.
AB  - Three highly informative markers genetically linked to Huntington's Disease (HD)
      were used for diagnosis of HD in Mexican patients, two polymorphic HindIII sites
      located at D4S10 locus and one VNTR marker at D4S111 locus (VNTR-111). Forty
      chromosomes from healthy subjects were tested in order to evaluate the
      informativeness of the probes. The RFLP HindIII 1 and 2 and the VNTR-111 probes
      showed a heterozygosity of 0%, 45%, and 60%, respectively. Five families were
      analyzed, of these, only in two the markers used were informative. In one of
      them, six members showed a decreased risk of inheritance of the mutant gene for
      Huntington's Disease with 95% accuracy (1).

PMID- 8867375
TI  - Nodal radiotherapy in refractory tuberculosis in an AIDS patient.
AB  - A 25-year-old female with transfusion-associated acquired immunodeficiency
      syndrome (AIDS) treated with zidovudine (AZT) developed cervical lymph node
      enlargement. The histological study disclosed granulomas and the culture revealed
      M. tuberculosis. The patient was treated with isoniazid, rifampicin and
      pirazynamide and the lymphadenomegaly resolved. Five years later, with a CD4 cell
      count of 245, the lymph node enlargement reappeared, the biopsy and special
      studies confirming tuberculosis (TB). She was then given ciprofloxacin,
      azithromycin, ethambutol, amikacin and pirazynamide without success. In two
      instances the enlarged nodes were surgically removed. Facing progressive
      obstruction of both the airway and the esophagus, localized radiotherapy (1800
      cGy in nine fractions) to the right aspect of the neck was delivered with
      dramatic resolution of the node enlargement; however, dissemination of the
      infection leading to a severe lung infiltration and respiratory failure ended the
      life of the patient.

PMID- 8867376
TI  - Seroprevalence of HTLV-I/II in blood donors in Monterrey, Mexico.
AB  - The prevalence of antibodies against human T-cell lymphotrophic virus (HTLV-I/II)
      in blood donors from the city of Monterrey, Mexico was investigated. We found
      that 4 out of 1017 sera (0.39%) reacted against HTLV-I/II, as determined by a
      passive agglutination test (PA). However, none of PA-positive sera reacted to
      HTLV-I/II specific polypeptides as demonstrated by Western blot. These findings
      indicate that the population of Monterrey has very low or no seroprevalence for
      HTLV-I/II.

PMID- 8867377
TI  - The epidemiology of Mycobacterium leprae: recent insight.
AB  - Leprosy is still a health problem in many countries. Because the causative
      organism, Mycobacterium leprae cannot be cultured in vitro, it is virtually
      impossible to assess exposure, and the onset of infection and disease. As a
      consequence, the chain of infection, considered as the relationships between M.
      leprae, transmission and human host, is poorly understood. Here, we discuss a
      number of organism-, host- and environmental-related factors which may be
      incriminated in the dynamic process of the development of leprosy disease. The
      use of modern molecular and immunological tools has become a valuable addition to
      epidemiological research. Understanding of the epidemiology of leprosy is a
      prerequisite for effective control of the disease.

PMID- 8867378
TI  - Cloning and characterization of the Alcaligenes eutrophus 2-oxoglutarate
      dehydrogenase complex.
AB  - Nucleotide sequence analysis of a 3.3-kb genomic EcoRI fragment and of relevant
      subfragments of a genomic 13.2-kb SmaI fragment of Alcaligenes eutrophus, which
      were identified by using a dihydrolipoamide dehydrogenase-specific DNA probe,
      revealed the structural genes of the 2-oxoglutarate dehydrogenase complex in a
      7.5-kb genomic region. The genes odhA (2850 bp), odhB (1248 bp), and odhL (1422
      bp), encoding 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide
      succinyltransferase (E2), and dihydrolipoamide dehydrogenase (E3), respectively,
      occur co-linearly in one gene cluster downstream of a putative -35/-10 promoter
      in the order odhA, odhB, and odhL. In comparison to other bacteria, the
      occurrence of genes for two E3 components for the pyruvate as well as for the 2
      oxoglutarate dehydrogenase complexes is unique. Heterologous expression of the A.
      eutrophus odh genes in E. coli XL1-Blue and in the kgdA mutant Pseudomonas putida
      JS347 was demonstrated by the occurrence of protein bands in electropherograms,
      by spectrometric detection of enzyme activities, and by phenotypic
      complementation, respectively.

PMID- 8867380
TI  - A chemiluminescence immunoassay for evaluation of Cryptosporidium parvum growth
      in vitro.
AB  - A chemiluminescence immunoassay (CLIA) was developed to detect Cryptosporidium
      parvum growth in Madin-Darby canine kidney (MDCK) cell cultures. Optimal results
      were obtained when MDCK cells were plated at a density of 1 x 10(4) cells/well
      (96-well plate) and maintained as a monolayer for 4 days prior to infection with
      2 x 10(4) parasites/well. Two compounds (paromomycin and maduramicin) were
      evaluated and shown to have selective activity against C. parvum in a dose
      dependent manner. There was excellent correlation between CLIA and
      immunofluorescence assay when assessing anti-C. parvum agents in MDCK cells. CLIA
      offers advantages over conventional enzyme-linked immunosorbent assay and
      immunofluorescence assay methods in that it is more sensitive and efficient. The
      combination of CLIA and MDCK culture provides an efficient tool for evaluating
      potential anti-cryptosporidial compounds prior to testing in animal models.

PMID- 8867379
TI  - In vitro anticryptosporidial activity of dinitroaniline herbicides.
AB  - Despite the evaluation of over 100 antimicrobial drugs, the diarrheal disease
      cryptosporidiosis has remained refractory to treatment. We report the evaluation
      of five dinitroaniline herbicides including trifluralin, profluralin, nitralin,
      pendimethalin, and fluchloralin for anticryptosporidial activity in an in vitro
      cultivation model of Cryptosporidium parvum. All five compounds exhibited
      significant anticryptosporidial activities with no corresponding evidence of
      toxicity. The most active compound was pendimethalin with an IC50 of 0.19 microM
      while nitralin was the least active with an IC50 of 4.5 microM. These compounds
      should be evaluated further in an animal model of cryptosporidiosis.

PMID- 8867381
TI  - Salmonella typhimurium InvA expression probed with a monoclonal antibody to the C
      terminal peptide of InvA.
AB  - The Salmonella typhimurium InvA protein is a component of a sec-independent
      secretion apparatus necessary for full virulence of the bacteria. We generated a
      monoclonal antibody to the C-terminal portion of the InvA protein that recognized
      proteins in S. typhimurium and weakly in Y. enterocolitica, but not in several
      other species of bacteria, including S. flexneri. S. typhimurium grown without
      agitation produced relatively constant amounts of membrane InvA throughout the
      growth cycle, whereas bacteria grown with agitation had a sharp increase in the
      amount of membrane InvA at late exponential phase. Levels of InvA present in
      Salmonella membranes under some growth conditions do not appear to correlate with
      levels of invasion under the same conditions.

PMID- 8867382
TI  - Characterization of an insertion sequence-like element identified in plasmid
      pCIT264 from Lactococcus lactis subsp. lactis biovar diacetylactis.
AB  - Plasmid pCIT264 from Lactococcus lactis subsp. lactis biovar diacetylactis (L.
      diacetylactis) contains an insertion sequence (IS)-like element located in the
      citrate utilization (citQRP) cluster. This 967-nucleotide long element is bounded
      by 17 bp perfect inverted repeats and contains an open reading frame (ORF1)
      composed of 296 codons, which could encode a transposase. Expression of the IS
      from pCIT264 generates two mRNAs of 2900 and 1900 nucleotides. The transcription
      is driven by the P3 promoter, composed of a -10 region located at the right end
      of the IS and of a -35 region positioned downstream of this element. The IS-like
      element (IS982) is present in seven copies in the L.diacetylactis genome. The
      copy present in pCIT264 is highly stable and does not promote rearrangements of
      the cit cluster. We suggest that the stable maintenance of the IS-like element in
      pCIT264 could be due to a translational control of the putative transposase by an
      antisense RNA.

PMID- 8867383
TI  - The activity of microcin E492 from Klebsiella pneumoniae is regulated by a
      microcin antagonist.
AB  - Microcin E492 is a polypeptide antibiotic that is produced and excreted by
      Klebsiella pneumoniae. Different growth conditions of the producer strain affect
      microcin activity. The production of a microcin antagonist is responsible for the
      changes in microcin activity. The microcin antagonist is induced when cells are
      iron-deprived, resulting in a low microcin activity. The microcin antagonist was
      purified using a procedure developed for the isolation of a catechol-type
      siderophore, and its activity was titrated using purified microcin. The
      inhibitory effect of the microcin antagonist is not observed when this compound
      is forming a complex with iron. The same inhibitory effect on microcin activity
      was obtained using purified enterochelin from Escherichia coli. The microcin
      antagonist was identified as enterochelin through thin-layer chromatography.

PMID- 8867384
TI  - Isolation of a gene encoding cysteine synthase from Flavobacterium K3-15.
AB  - The cysteine synthase gene (cysK) from Flavobacterium K3-15 was cloned and
      sequenced. The gene exhibits 30-50% identity to known cysteine synthases on both
      the DNA and the amino acid levels. The pyridoxal phosphate binding site of the
      enzyme is part of a conserved motif comprising seven amino acids (SIKDRIA). The
      lys31 residue of the flavobacterial enzyme is conserved in all known cysteine
      synthases. The cysK gene from Flavobacterium K3-15 was heterologously expressed
      and the gene product identified by immunoblotting and determination of the enzyme
      activity.

PMID- 8867385
TI  - Analysis of nucleotide methylation in DNA from Corynebacterium glutamicum and
      related species.
AB  - Plasmid DNA (pCSL17) isolated from Corynebacterium glutamicum transformed
      recipient McrBC+ strains of Escherichia coli with lower efficiency than McrBC-
      strains, confirming a previous report by Tauch et al. (FEMS Microbiol. Lett. 123
      (1994) 343-348) which inferred that C. glutamicum DNA contains methylcytidine.
      Analysis of nucleotides in C. glutamicum-derived chromosomal and plasmid DNA
      failed to detect significant levels of methylated adenosine, but methylated
      cytidine was readily detected. Restriction enzymes which are inhibited by the
      presence of methylcytidine in their recognition sequence failed to cut pCSL17
      from C. glutamicum, whereas enzymes which require methylation at adenosine in
      GATC sequences failed to cut. Failure of HaeIII to cut two specific sites of C.
      glutamicum-derived pCSL17 identified the first cytidine in the sequence GGCCGC as
      one target of methylation in this species, which contains the methyltransferase
      recognition sequence. Although Brevibacterium lactofermentum-derived DNA showed a
      similar methylation pattern by HPLC analysis, HaeIII cleaved these GGCCGC sites,
      suggesting differences in the specificity of methylation between these two
      species. Results for all analyses of B. flavum DNA were identical to those for C.
      glutamicum.

PMID- 8867386
TI  - Variable numbers of rRNA gene operons in Bacillus cereus strains.
AB  - Ribosomal RNA operon organisation was analysed in two Bacillus cereus strains of
      different chromosome size, ATCC 10987 (5.4 Mb) and F0837/76 (2.4 Mb). We
      estimated that there were twelve and nine copies of the rRNA operons in these two
      strains, respectively. In B. cereus ATCC 10987 six rRNA operons were less than 10
      kb apart, while in B. cereus F0837/76 four rRNA operons were similarly clustered.
      The origin of replication was located in the vicinity of a rRNA operon in both
      strains.

PMID- 8867387
TI  - Computer screens and brain cancer.
AB  - Concern has recently been expressed in Australia, both in the media and at the
      federal government level, over possible links between screen-based computer use
      and cancer, brain tumour in particular. The screen emissions assumed to be the
      sources of the putative hazard are the magnetic fields responsible for horizontal
      and vertical scanning of the display. Time-varying fluctuations in these magnetic
      fields induce electrical current flows in exposed tissues. This paper estimates
      that the induced current densities in the brain of the computer user are up to 1
      mA/m2 (due to the vertical flyback). Corresponding values for other electrical
      appliances or installations are in general much less than this. The
      epidemiological literature shows no obvious signs of a sudden increase in brain
      tumour incidence, but the widespread use of computers is a relatively recent
      phenomenon. The occupational use of other equipment based on cathode ray tubes
      (such as TV repair) has a much longer history and has been statistically linked
      to brain tumour in some studies. A number of factors make this an unreliable
      indicator of the risk from computer screens, however.

PMID- 8867388
TI  - The standardisation of fluorine-18.
AB  - The Australian Nuclear Science and Technology Organisation (ANSTO) maintains and
      disseminates the Australian standards of activity measurement. The standards
      include all nuclear medicine gamma-emitters and pure positron emitters.
      Calibration factors for the ANSTO 4 pi ionisation chamber for pure positron
      emitters have been traditionally determined from primary standardisations of
      cobalt-60 and sodium-22. Activity estimates of pure beta emitters have been
      previously determined by using 4 pi beta-gamma coincidence (efficiency tracer)
      counting. This method was adapted to test activity estimates of short-lived pure
      positron emitters made using the 4 pi ionisation chamber. Detailed are methods
      whereby the activity of fluorine-18 can be measured. The first method is an
      efficiency tracing method developed in this work. The method directly tests 4 pi
      ionisation chamber fluorine-18 activity estimates. The gamma-gamma method was
      carried out to confirm this.

PMID- 8867389
TI  - Physical and subjective evaluation of a three-detector (TRIAD 88) SPECT system.
AB  - The three-detector TRIAD 88 is a variable cylindrical FOV whole-body SPECT system
      designed for both brain as well as body organ imaging. The system performance was
      assessed in terms of physical indices and clinical quality. Measures of low
      contrast resolution using contrast-detail curves, high contrast resolution using
      LSFs and associated frequency descriptors, display characteristics, system
      sensitivity, energy resolution and uniformity analysis were utilized. In
      addition, images of Carlson phantom, Hoffman brain phantom and clinical brain
      images were used to compare two collimators subjectively. Measurements and
      calculations were obtained for two sets of parallel hole collimators, i.e.,
      LEUR_PAR and LEHR_PAR. Of special interest is the consistency among the three
      detectors. The planar and volume sensitivities for the LEUR_PAR collimator were
      about 58% of those of the LEHR_PAR collimator. The planar spatial resolution of
      the two collimators differed by about 14%. The display was characterized by a
      logistic model H & D curve. The planar contrast-detail curves demonstrated no
      statistical difference in lesion detectability between the two collimator types,
      however SPECT phantom and clinical images demonstrated improved performance with
      the LEUR_PAR collimator. Images of Hoffman single slice brain and Carlson
      phantoms and Tc-99m (HMPAO) brain images demonstrated excellent image quality.
      There was similarity in performance parameters of the three detector heads.

PMID- 8867390
TI  - Preliminary expansion of the resonant recognition model to incorporate multi
      variable analysis.
AB  - The Resonant Recognition Model (rrm) uses digital signal processing methods to
      investigate protein structure-function; and links the biological function of
      protein families to unique characteristic frequencies. The rrm originally used a
      single set of variables: the electron ion interaction potential (EIIP). Here the
      rrm has been expanded to include 242 sets of variables to analyse a sample of
      protein families. Despite the evident increase in complexity of the data,
      distinguishing patterns can be observed between the different protein families.
      The thus-obtained Signature Profiles (SP) indicate that proteins having similar
      overall functions may be identifiable and differentiated from others by their
      characteristic frequency signatures far more readily than with the single
      variable rrm spectra.

PMID- 8867391
TI  - Total skin electron therapy at two energies on a linear accelerator.
AB  - We have implemented the AAPM Task Group 30 recommendations with respect to Total
      Skin Electron Therapy (TSET) for the treatment of Mycosis Fungoides. Extensive
      measurements have been performed on the Varian 2100c linear accelerator with a
      water equivalent phantom, cylindrical phantoms and an anthropomorphic phantom to
      validate the 12 beam technique and to measure calibration factors. The technique
      was developed at 2.5 MeV and 3.5 MeV (mean energy at the surface) with the energy
      degrading screen at 30 cm from the patient. Field flatness over the treatment
      area was within +/- 3% with no significant regional variation of energy. The
      bremstrahlung contamination was .06-1.2%. The absolute calibration of absorbed
      dose to the patient required the measurement of the ratio "skin dose to
      calibration point dose", this was confirmed by measurements with a parallel plate
      ionization chamber and thermoluminescence dosimetry. The results indicate the
      care that must be taken with ionization chamber measurements under TSET condition
      to avoid erroneous readings due to the "polarity effect". A protocol is suggested
      for the practical implementation and quality assurance of the technique. The
      results of two successful treatments are presented and compared with the
      predicted results from phantoms.

PMID- 8867392
TI  - Spinal manipulation as a valid treatment for low back pain.
AB  - The practice of chiropractic has been regulated in the State of Delaware since
      1937. Since that time, the battle lines in the state between medicine and
      chiropractic have been drawn. This war has existed on both the political and
      clinical fronts, and although it has always been believed by the chiropractic
      profession that once the "scientific evidence" of the benefit of chiropractic was
      proven, the war would end. This has not occurred to the extent believed. Even
      with its 1980 victory over the AMA, chiropractic has still been unable to achieve
      full acceptance as a clinical discipline among other professions. Many hospitals
      in this country have opened their doors to DCs. This by and large, has solely
      been for economic reasons and not as a recognition of the clinical benefit of
      manipulation. There is, however, a growing population of primary care physicians
      and researchers suggesting the benefit of manipulation for low back pain as well
      as suggesting that increased cooperation between MDs and DCs could be of extreme
      benefit to the patient population at large. This group continues to be in the
      minority. However, with increased knowledge of the benefits of spinal
      manipulation and the scientific evidence that now exists to support its efficacy,
      it is now believed that this interprofessional referral pattern will increase. In
      addition, many managed care programs now require primary care physicians to
      determine the necessity for referral to a chiropractor, thus causing a need for
      the primary physician to have some knowledge of spinal manipulation. This paper
      is presented to inform the physician community of Delaware of some of the
      evidence pointing to the efficacy of spinal manipulation as a treatment for low
      back pain.

PMID- 8867393
TI  - Recent advances in the diagnosis of breast cancer: scintimammography.

PMID- 8867394
TI  - Operative management of hepatic injuries.
AB  - Seventy-seven cases of hepatic trauma diagnosed during exploratory laparotomy
      were retrospectively studied. Blunt trauma comprised the majority of cases.
      Seventy-five per cent of cases had associated injuries and 58 per cent were in
      shock on arrival. The mortality rate was 19 per cent. Exsanguination and
      associated head injuries were the major causes of death. Aggressive resuscitation
      and immediate exploratory laparotomy are not overemphasized if survival is
      expected. During operation, suture ligature of the bleeding points or
      hepatorrhaphy stopped the bleeding in most circumstances. Hepatic artery ligation
      was seldom performed. Omental packing of the liver wounds was an effective
      procedure. Anatomical hepatic resections were performed with a relatively high
      mortality rate. Debridement of devitalized liver tissue should be done routinely
      to prevent postoperative infection. Perihepatic packing was a useful procedure
      when termination of the operation was considered necessary in order to prevent
      the development of hypothermia, acidosis and coagulopathy.

PMID- 8867395
TI  - Hormonal replacement and lipid changes in postmenopausal women.
AB  - To assess the effect of hormonal replacement therapy on lipid changes,
      measurement of serum total cholesterol (TC), triglycerides (TG), low density
      lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein A-1 (Apo-A) and
      apolipoprotein B (Apo-B) was performed on 93 postmenopausal women. Women in the
      study group (HRT) (51/93) received estrogen with or without progestin. The
      control group (Non-HRT) (42/93) did not receive any hormone regimen. The
      measurement was done at 0, 6 and 12 months. The results revealed that
      triglyceride increased significantly more in the non-HRT than the HRT group at 6
      and 12 months. (Non-HRT: +21.7%, +21.7%; HRT: -2.8%, +2.4%, respectively P <
      0.05). However, there was no significant difference in changes of other lipid
      profiles between the two groups at 6 and 12 months (Non-HRT: TC -2.7%, +0.7%, HDL
      +2.9%, +5.1%, LDL -5.2%, -4.1%, Apo-A +0.5%, +0.9%, Apo-B +3.8%, +1.3%: HRT: TC 
      1.4%, -2.8%, HDL +4.7%, +6.2%, LDL -1.5%, -4.9%, Apo-A -0.9%, +1.6%, Apo-B -2.6%,
      -1.6%, respectively P > 0.05). The paradoxical changes of triglyceride and HDL
      might partly be explained by the effect of progestins used in this study.

PMID- 8867396
TI  - Perinatal mortality Chiang Rai Prachanukroh Hospital 1992-1994.

PMID- 8867397
TI  - Early nutritional support in severe traumatic patients.
AB  - Multiple trauma is associated with altered metabolism, wasting of the lean body
      mass and compromised wound healing. Nutritional support is one way to improve the
      condition of these critically ill patients. We performed a prospective randomized
      study on the effect of early nutritional support in severely injured patients
      admitted to the Division of Traumatic Surgery, Siriraj Hospital between June 1992
      and January 1994. Thirty-eight severe traumatic patients with ISS between 20-40
      were randomly divided into control and study group. The 17 patients in the
      control group were treated in the conventional method with administration of hypo
      caloric intravenous regimen and supplement with oral diet as soon as the bowel
      function was returned. The 21 patients of the study group were fed either by
      enteral or parenteral feeding or both with an appropriate caloric and protein
      requirement as soon as hemodynamic status was stabilized. We found the study
      group had a lower mortality rate, a lower complication rate, a shorter period of
      ICU stay, and an earlier weaning from the ventilator than the control group. The
      study group also lost less weight than the control group. Nitrogen balance in the
      study group was significantly lower than the control group.

PMID- 8867398
TI  - The accuracy of mammography: a comparison with fine needle aspiration cytology.
AB  - A retrospective study of 212 patients from the National Cancer Institute of
      Thailand were analysed. All of these patients had undergone mammographic, fine
      needle aspiration cytologic and histopathologic diagnosis during the year 1988
      1989. They presented with breast lesions, either ill-defined or well defined
      masses. The mammographic diagnosis were compared with fine needle aspiration
      cytologic diagnosis. The sensitivity, specificity and accuracy of mammography
      were 89.83 per cent, 94.77 per cent and 93.39 per cent respectively while the
      fine needle aspiration cytology were 98.30 per cent, 98.69 per cent and 98.58 per
      cent. Although this study revealed high accuracy of mammography, it was less
      accurate than the fine needle aspiration cytology and similar to many documented
      reports. The study of efficacy of mammographic diagnosis is the way to evaluate
      the practice of radiologists, technologists and mammographic techniques. The
      gradual development of these important factors lead to obtain higher accuracy of
      mammographic diagnosis.

PMID- 8867399
TI  - Intracavitary irradiation of nasopharyngeal carcinoma using Ir-192 in Foley's
      catheter.
AB  - 1. HDR Ir-192 intracavitary insertion in Foley's catheter for a boostered
      radiation dose to the nasopharynx is a very simple and safe technique and may
      increase the local control and survival of the patients. 2. Intracavitary
      brachytherapy should be done in all cases of NPC after the completion of external
      irradiation to increase local control that may lead to long term survival of the
      patients.

PMID- 8867400
TI  - Maternal antibodies against rabies in Thai puppies. A preliminary study.
AB  - Serum antibodies to rabies virus were measured in 32 Thai puppies before primary
      vaccination. Only five showed evidence of rabies antibody by ELISA testing and
      they had no rabies virus neutralizing activity detectable by RFFIT. Immunologic
      ignorance of these young dogs leaves a large part of the canine population
      susceptible to rabies. This could be one reason for the failure of canine rabies
      control efforts in Thailand.

PMID- 8867401
TI  - Bilateral tubal pregnancy following in vitro fertilization and embryo transfer.
AB  - We have presented a case of bilateral tubal pregnancy following in vitro
      fertilization and embryo transfer. The most likely cause, in our opinion, is
      'spray effect' which was discussed. The diagnosis of ectopic pregnancy must
      always be kept in mind in IVF&ET program, due to its high incidence of occurrence
      compared to natural conception. Although the incidence of bilateral tubal
      pregnancy is not high, one should identify the opposite adnexa when tubal
      pregnancy is diagnosed in an IVF&ET patient. Early diagnosis is essential for
      prevention of significant maternal morbidity and mortality.

PMID- 8867403
TI  - Totally extraperitoneal laparoscopic lumbar sympathectomy: an initial case
      report.
AB  - A 27-year-old man with a diagnosis of Buerger's disease presented with
      vasospastic symptoms of coldness and pain at rest of his right foot. Physical
      examination of his affected limb revealed absent popliteal pulse, cool skin
      hyperhidrosis and dry gangrene of the big toe. He had been operated on for a
      ruptured liver and liver abscess 20 years ago. He was scheduled for totally
      extraperitoneal laparoscopic lumbar sympathectomy on July 26, 1994. The technique
      was performed under general anesthesia and the patient was put in a supine
      position with slight extension between the rib and the iliac crest. The working
      space was created by digital blunt dissection and direct insufflation of carbon
      dioxide. The right sympathetic trunk was found between the medial edge of the
      psoas muscle and inferior vena cava. The L2, L3, L4 sympathetic ganglia were
      identified above the vertebral column and meticulously dissected cephalocaudally.
      Based on the concept of traditional approach, we believe that this laparoscopic
      technique is relatively safe and should become the procedure of choice in the
      future.

PMID- 8867402
TI  - Granulomatous interstitial nephritis in renal transplant recipient.
AB  - Tuberculosis of a transplanted kidney is a rare and serious complication. Search
      for renal tuberculosis as the cause of deterioration of graft function is
      mandatory in a renal transplant recipient with tuberculosis of other organs e.g.
      pulmonary tuberculosis in this patient. Renal histopathology is required for the
      diagnosis. Treatment with anti-tuberculosis drugs can improve renal function.
      Drug interactions should be considered when rifampicin is administered with
      cyclosporin A.

PMID- 8867404
TI  - Psittacosis pneumonia: a case report and review of the literature.
AB  - A case of acute, severe pneumonia with respiratory insufficiency due to Chlamydia
      psittaci is described. Rapid improvement with tetracycline therapy in all
      symptoms and arterial blood gases is demonstrated. The diagnosis of psittacosis
      was secured by both cultivation and serological verification. A comprehensive
      review of the literature is appended. The present report attests to the need for
      inclusion of C. psittaci as a possible aetiologic agent causing fulminating
      community-acquired pneumonia.

PMID- 8867405
TI  - Hepatic artery aneurysm: a case report.
AB  - Hepatic artery aneurysm should be considered in the differential diagnosis of
      unexplained upper abdominal pain. Diagnosis can be made by using color-flow
      Doppler ultrasound but selective angiography is also needed. Aggressive treatment
      is necessary.

PMID- 8867406
TI  - Crusted scabies associated with systemic lupus erythematosus: response to benzyl
      benzoate therapy.
AB  - A 30-year-old Thai woman with systemic lupus erythematosus developed crusting,
      erythematous scaling plaques on the scalp and neck. Histologic section showed
      numerous mites in the stratum corneum. The diagnosis was further confirmed by
      identification of Sarcoptes scabiei in scraping and potassium hydroxide
      preparations made from the cutaneous lesions. After applications of 25 per cent
      benzyl benzoate for one month, there was complete resolution of the parasitic
      infestation.

PMID- 8867407
TI  - A conversation with C. Everett Koop, M.D.. Interview by Stephen J. Jay.

PMID- 8867408
TI  - A conversation with Ronald M. Davis, M.D.. Interview by Bob Carlson.

PMID- 8867409
TI  - ASSIST: making a difference in Indiana.

PMID- 8867410
TI  - Tobacco control and the AMA: health, policy and politics.

PMID- 8867411
TI  - Trends of public opinion on tobacco use and public policy.
AB  - This study examined the trends and stability of public opinion related to tobacco
      use and raising tobacco taxes in Indiana. Using a structured questionnaire, a
      sample of 800 households was randomly selected, and the adults were interviewed
      by telephone in 1989, 1990 and 1992 by the Indiana University Center for Survey
      Research. The data were subjected to descriptive and chi-square statistical
      procedures. The results of the study indicate that more than 80% agreed that
      secondhand smoke is a health threat, and the opinions remained practically stable
      for the duration of the study. Most respondents agreed that public places should
      be required to have nonsmoking areas. Further, most people favored a tax increase
      on cigarettes, and there was an upward trend toward more people favoring a tax
      increase in recent years. It was concluded that the tax on tobacco should be
      increased for public health reasons.

PMID- 8867412
TI  - Tobacco use by Indiana children and adolescents.
AB  - Data from a five-year, longitudinal survey of cigarette smoking and smokeless
      tobacco use by Indiana children and adolescents are presented. A four-page, self
      contained questionnaire was used to collect anonymous information from more than
      240,000 students in grades six through 12. Indiana students reported prevalence
      levels 20% to 50% higher than levels reported in comparable national surveys.
      Perceived risk of physical or psychological harm was the single best statistical
      predictor of whether or not a student would choose to use tobacco. Tobacco use
      was statistically linked to increased use of illicit drugs. Physicians can play a
      powerful role in influencing a patient's perception of the risks associated with
      cigarette smoking.

PMID- 8867413
TI  - Effects of tobacco use on the health of Indiana citizens.
AB  - In Indiana, the lung cancer mortality rate is almost equal to the incidence rate.
      The mortality rate from lung cancer in men is almost four times higher than for
      any other cancer. In women, the mortality rate is 20% higher than the mortality
      rate for breast cancer. In Indiana, black men have the highest death and
      incidence rates, followed by white men, black women, then white women. There are
      no early warning signs for lung cancer; there is no recommended screening
      mechanism; there is no uniformly effective treatment. Unlike most cancers, the
      primary cause of lung cancer is a well known behavioral factor: smoking. Smoking
      prevalence is higher in Indiana than in the United States for both men and women.

PMID- 8867414
TI  - Indiana family physician attitudes and practices concerning smoking cessation.
AB  - Most physicians are aware of the health benefits of smoking cessation and agree
      they have a responsibility to help smokers quit. Many physicians, however, do not
      regularly address smoking cessation with their patients. Questionnaires were sent
      to 2,095 family practice physicians in Indiana. Information obtained included:
      demographic data; office-based smoking cessation practices; counseling; and
      physicians' perceptions of intervention outcomes. Most physicians (86%) asked new
      patients if they smoked, and 23% questioned patients about their exposure to
      passive smoke. Younger physicians, female physicians and urban physicians were
      more likely to ask new patients if they smoked. A formal smoking cessation
      program was used by 28% of the responding physicians. Among those not using a
      program, 7% reported plans to implement one in the coming year, 40% were not
      planning to implement one, and 53% were unsure. Physician and practice
      characteristics were not correlated with the use of smoking cessation programs.
      Only 11% of physicians considered their smoking cessation counseling skills to be
      excellent; 27% indicated the need for improvement in skills. One-half (52%)
      believed their counseling efforts were effective; almost half (45%) believed that
      current reimbursement policies limited their involvement in smoking cessation
      interventions. Most respondents have not instituted smoking cessation programs in
      their practices. It is likely that a combination of strategies, including both
      undergraduate, graduate and continuing medical education programs and reform in
      reimbursement practices for cessation programs, will be required to achieve
      significant increases in long-term smoking abstinence rates.

PMID- 8867415
TI  - Workplace tobacco interventions.
AB  - Health promotion programs are becoming an integral part of work site activities.
      Recent data from Indiana businesses suggest that smoking is a leading concern. An
      objective has been adopted by the Indiana Chamber of Commerce that states that
      the number of employers with work site smoking cessation policies should
      increase. Smoking control and cessation programs implemented in industry have
      contributed to a decrease in the number of smokers and in the health risks of
      nonsmokers exposed to environmental tobacco smoke. This report describes the
      effectiveness of work site smoking control programs.

PMID- 8867416
TI  - Racial differences in the impact of smoking-attributable disease on health care
      costs in Indiana.
AB  - The purpose of this investigation was to estimate the direct health care costs
      attributable to smoking in Indiana and address these costs in the context of the
      differential health impact of tobacco use on minorities. Estimates of direct
      health care costs for smoking in 1990 were calculated using the Smoking
      Attributable Morbidity and Mortality and Economic Costs (SAMMEC 2.1) computer
      based program developed by the Centers for Disease Control and Prevention. The
      proportion of direct health care costs attributable to smoking were calculated by
      evaluating personal health expenditures from five cost centers including
      hospitalization, physician services, services of other health practitioners,
      nursing home care and drugs. Study findings indicate that direct health care
      costs were more than $700 million in 1990. Health care spending among whites
      accounted for 53% of total costs. Per capita costs among smokers and nonsmokers >
      or = 35 years of age amounted to $278. Although whites accounted for the majority
      of direct health care costs attributable to smoking, per capita costs were higher
      among African Americans compared to whites, reflecting the differential smoking
      attributable mortality rates experienced by these two groups.

PMID- 8867417
TI  - Smoking cessation in primary care.

PMID- 8867418
TI  - Smokeless tobacco usage: a growing and menacing addiction among Hoosier children
      and young adults.
AB  - During the past 25 years, the consumption of chewing tobacco and moist snuff has
      been increasing in frequency, especially among the youth. Smokeless tobacco (ST)
      use among Indiana youngsters is higher than its use among youngsters nationally.
      More than 10% of current Indiana high school junior and senior female students
      report some ST usage. ST ingestion causes addiction and serious health
      consequences, including various forms of cancer and significant dental diseases.
      It is not a safe alternative to cigarette smoking. Nicotine levels in ST are very
      high, and ST intake is rapidly addicting. Tobacco companies have been accused of
      "graduating" youthful customers from flavored lower-nicotine "starter" products
      to forms that contain a more highly concentrated nicotine content. Clinicians
      should routinely ask children, teens and adults about ST use. Early intervention
      in youth who are experimenting with ST or using "starter" products may prevent
      addiction and disease. Physicians should be alert to the intraoral physical signs
      of ST use. To strengthen their tobacco intervention skills, physicians should
      require continuing education training regarding ST.

PMID- 8867419
TI  - Best practices for smoking cessation intervention for hospitalized patients.
AB  - A multi-disciplinary workgroup of health care professionals and consumers has
      developed evidence-based best practices guidelines, an algorithm and clinical
      pathways for smoking cessation intervention for hospitalized patients. These
      practice recommendations can be adapted for implementation in managed care
      settings.

PMID- 8867420
TI  - The Indiana Prenatal Substance Use Prevention Program: its impact on smoking
      cessation among high-risk pregnant women.
AB  - The Indiana Prenatal Substance Use Prevention Program (PSUPP) was established in
      1988 to help pregnant women quit cigarette smoking as well as alcohol and drugs.
      PSUPP directors implement the Screen, Intervene and Follow-up (SIF) model to
      assess substance use and provide services to help clients stop smoking. During
      fiscal year 1995, almost 25,000 individuals were impacted directly or indirectly
      by the PSUPP. Of these, 1,334 pregnant women were screened for substance use by
      PSUPP. Of the 987 women identified with a known substance use risk factor, 42.4%
      (418) were high-risk smokers (more than five cigarettes per day) and 9.9% (98)
      were medium-risk smokers (smoking between one and four cigarettes per day). PSUPP
      directors counseled their high/medium risk smokers an average of four times
      during their pregnancy. The PSUPP appears to be effective in getting high-risk
      smokers to change their smoking behavior during their pregnancy. Approximately
      one-half (49.9%) of the 516 high- or medium-risk smokers decreased or quit
      smoking while participating in the PSUPP. When surveyed, about 80% of the PSUPP
      participants stated that the knowledge they gained through PSUPP relative to
      tobacco use was "very helpful." Only two-thirds of the PSUPP clients responded
      that they "strongly agreed" with the statement that tobacco use causes babies to
      have a lower birth weight. While pregnancy may provide the "teachable moment" for
      women who smoke, more attention needs to be placed on making women more aware of
      the risks involved with smoking during pregnancy.

PMID- 8867421
TI  - Tobacco education in low-literacy individuals.
AB  - Approximately 20% of the adult population in the United States have low-literacy
      skills. The subpopulations with the highest incidence of low literacy are nearly
      identical to those with the highest prevalence of tobacco use. Low-literacy
      smokers are more likely to underestimate the risks related to tobacco use, have
      less social pressure and support to quit smoking, may experience more life stress
      and consequently rely more heavily on nicotine use for stress reduction and
      require more assistance in developing a sense of self-efficacy. This indicates a
      need to modify smoking cessation methods of counselling, content and selection of
      educational materials for the marginally literate. Currently available low
      literacy materials are listed, and suggestions for adjusting or developing
      materials are made.

PMID- 8867422
TI  - Indiana laws regarding tobacco control.

PMID- 8867423
TI  - Ethical responsibilities of physicians in tobacco control.

PMID- 8867424
TI  - Tobacco curriculum for medical students, residents and practicing physicians.
AB  - Smoking and other tobacco exposure have been recognized for several decades as
      the most significant preventable factors in premature morbidity and mortality.
      Most physicians believe they should address the issue of tobacco intake with
      their patients but are rarely provided with adequate training or support to do so
      effectively. Recent research identifies several ways in which physicians can have
      substantial impact on patient smoking rates, by use of very brief patient
      centered counseling and by prescribing nicotine replacement therapies. This paper
      describes a model curriculum for medical students, residents, medical faculty and
      community physicians that can be integrated into current training and teaching
      practices. The goal is to create a "preventive" intervention perspective to
      smoking that is effective, practical, efficacious and cost-effective.

PMID- 8867425
TI  - Tobacco free at the Indianapolis 500.
AB  - Most children are highly impressionable and easily influenced, particularly by
      people they admire. Role models in sports and entertainment who publicly use or
      commercially promote tobacco products potentially influence children to do the
      same. Motorsports events are saturated with tobacco sponsorship. We describe the
      counter-promotion of tobacco at the famed Indianapolis 500 and suggest other
      venues to continue this "Tobacco Free America" theme.

PMID- 8867426
TI  - [High dosage administration of paramagnetic contrast media in diagnosis of focal
      brain lesions].
AB  - In analogy with high-dose contrast-enhanced CT, there have been a few studies
      during recent years that have dealt with high-dose paramagnetic contrast dyes in
      MRI. One reason for these studies was the development of new and low-osmolar
      contrast agents in the MR field. Depending on the clinical problem, a high-dose
      contrast study in MRI is rarely indicated: (1) in metastatic disease, MR imaging
      with high-dose contrast material is indicated when the standard dose study is
      negative or only shows a solitary cerebral lesion or a number of lesions just
      suitable for radiosurgery; (2) in patients with malignant glioma the high-dose
      study allows better definition of the tumor margins. If a radical surgical
      approach is planned, the diagnostic potential should be fully used; if only a
      biopsy or subtotal debulking is planned, a standard dose study is enough. (3) in
      patients with MS, a high-dose study is only recommended within therapeutic trials
      in which the number of active plaques is a primary variable.

PMID- 8867427
TI  - [Perfusion studies with paramagnetic contrast media and rapid pulse sequences in
      cerebrovascular diseases and brain tumors].
AB  - The combination of fast MR sequences and rapid i.v. injection of paramagnetic
      contrast media provides information on cerebral perfusion. MR-perfusion imaging
      primarily depicts the relative cerebral blood volume. The aim of this study was
      to test whether MR-perfusion imaging with a clinical MR scanner using a standard
      2D-FLASH sequence provides clinically relevant information on patients with
      cerebrovascular diseases and brain tumors. Brain infarctions, lesions in cerebral
      microangiopathy and occlusions of the carotid artery with very poor
      collateralization showed definite differences in perfusion imaging compared with
      normal controls. However, our results show that acceleration of the imaging
      sequence and optimization of the contrast bolus and data processing are
      prerequisites for the clinical use of this method, which in principle may provide
      information on the absolute cerebral blood volume and even blood flow.

PMID- 8867428
TI  - Contrast-enhanced MR angiography.
AB  - Despite many optimizations, the current limitations of plain MR angiography
      include: saturation that impairs the visualization of veins and arteries with
      slow flow and spin-dephasing signal voids in locations with turbulent flow.
      Recently, the use of contrast agents has been proposed to cope with these
      remaining problems. Because of induced shortening of the T1 of the blood,
      saturation in the blood vessels is overcome. As a result, arteries and veins are
      visualized with the same signal intensity, which makes the technique less flow
      dependent. In combination with short T1-weighted acquisitions, today CE MRA can
      be obtained while the patient is holding his breath. This last approach is most
      promising for abdominal applications since the respiratory motion can be frozen.
      As these acquisitions also use very short echo times, spin dephasing can be
      reduced. In conclusion, the use of contrast agents has greatly increased the
      clinical usefulness of MR angiography.

PMID- 8867430
TI  - [Contrast media for magnetic resonance tomographic lymph node diagnosis (MR
      lymphography)].
AB  - In MR-imaging, similar to computed tomography, diagnosis of metastatic lymph-node
      disease is based on lymph-node sizes, and thereby it is non-specific. Super
      paramagnetic iron oxide as a potential contrast medium for MR-lymphography
      accumulate in normal lymph node tissue after endolymphatic, interstitial and, in
      case of very small particles, after intravenous injection. No accumulation
      occures in lymph node metastases. Lymph-node metastases can be detected by all
      three injection techniques. It has been shown experimentally, that in particular
      small metastases can be detected in normal sized lymph nodes. However, MR
      lymphography also has inherent methodologic problems, as there may occure an
      uneven distribution of the contrast medium between different lymph-node groups.
      The experimental results with endolymphatic, interstitial, and intravenous MR
      lymphography as well as first clinical results with intravenous contrast medium
      injection are presented and discussed.

PMID- 8867429
TI  - [New MR contrast media in liver diagnosis. Initial clinical results with
      hepatobiliary Eovist (gadolinium-EOB-DTPA) and RES-specific Resovist (SH U 555
      A)].
AB  - The purpose of this work is to describe our initial clinical experience (in 66
      patients) with Resovist and Eovist, two new liver-specific MR contrast agents. We
      focus our report on safety aspects, dose finding, and optimization and technical
      parameters. Both contrast agents were well tolerated and improved the
      detectability of focal liver lesions. With Resovist, postcontrast MRI may be
      started as early as 10 min following injection. The dose of 8 mumol Fe/kg
      bodyweight was sufficient to achieve diagnostic tumor-liver contrast levels.
      Since Eovist can also be administered as a bolus, dynamic enhancement patterns
      may be studied for tumor characterization as well. Breath-hold T1-weighted FLASH
      images were superior to other T1-weighted techniques with and without fat
      saturation.

PMID- 8867431
TI  - [Use of gadoteridol in MR diagnosis of rheumatoid changes in the joints].
AB  - PURPOSE: To investigate the diagnostic and clinical usefulness of a new non
      ionic, hydrophilic gadolinium (III) chelate [Gd(HP-DO3A), gadoteridol, ProHance]
      and to compare it with Gd-DTPA (gadopentetate dimeglumine, Magnevist). METHODS:
      In a Phase III clinical trial, 20 patients with rheumatic joint disease were
      examined before and after intravenous administration of gadoteridol in two
      different doses (0.1 and 0.3 mmol/kg bodyweight). Magnetic resonance imaging
      (MRI) was performed at 1.5 T with T1-weighted FLASH and T2-weighted spin echo
      sequences. Fourteen patients were examined with gadopentetate dimeglumine for
      comparison. Dynamic changes of signal intensity in the joints and muscle tissue
      were determined quantitatively. RESULTS: No significant changes in cardiovascular
      data and no adverse effects occurred after injection of gadoteridol. The 0.3
      mmol/kg dose showed no advantage in diagnostic contrast over the 0.1 mmol/kg
      dose. No significant differences (p > 0.01) were noted between gadoteridol and
      gadopentetate dimeglumine in patients with early rheumatoid arthritis.
      CONCLUSION: Gadoteridol proved useful in the detection of early rheumatoid
      arthritis. No significant differences were observed between the two gadoteridol
      doses. There were no diagnostically relevant differences between gadoteridol and
      gadopentetate dimeglumine.

PMID- 8867432
TI  - [High dosage Gd-DPTA-BMA (Gadodiamid) administration in diagnosis and therapeutic
      monitoring of malignant bone tumors].
AB  - PURPOSE: To evaluate the efficacy of high-dose Gd-DTPA-BMA (gadodiamide,
      Omniscan) as a contrast for magnetic resonance imaging of malignant bone tumors
      and the use of high-dose dynamic studies for predicting the response to pre
      operative chemotherapy. MATERIALS AND METHODS: Examinations were performed in 22
      patients with suspected malignant bone tumor on a 1.5 T system. In 8 cases a
      follow-up examination was done after preoperative chemotherapy. Static studies
      included Pd- and T2-weighted spin-echo sequences as well as T1-weighted spin-echo
      sequences, obtained pre- and post-contrast. Dynamic studies were performed using
      a FLASH 2D-gradient-echo sequence (TR 40 ms/TE 10 ms, 90 degrees flip angle)
      every 20 s after intravenous bolus injection of Gd-DTPA-BMA (0.3 mmol/kg body
      weight). MR images were evaluated qualitatively by visual assessment of
      conspicuity size, extraosseous delineation and structure of the lesion and
      quantitatively by measurement of the signal intensities and calculation of the
      relative increase in signal intensity. RESULTS: Qualitative image analysis showed
      best demonstration of the lesions on contrast-enhanced T1-weighted images.
      Comparison of T1-weighted pre- and postcontrast spin-echo sequences revealed
      significantly better assessment of tumor structure after administration of
      contrast media. After preoperative chemotherapy, all responders showed a markedly
      stronger reduction in relative increase in signal intensity in dynamic studies
      compared to nonresponders. CONCLUSION: Gd-DTPA-BMA is effective for magnetic
      resonance imaging of musculoskeletal lesions and improves assessment of the tumor
      structure. Dynamic studies may help to predict the response to preoperative
      chemotherapy.

PMID- 8867433
TI  - [Development and experimental use of receptor-specific MR contrast media].
AB  - The authors describe the feasibility of developing receptor-specific MR contrast
      agents for the improved detection of pathology and assessment of organ function.
      Receptor specificity of MR contrast agents can be achieved by binding of receptor
      specific carriers to ligands. This concept leads towards a decrease in dose and
      thus in toxicity. Specific attachment to parenchymal cells improves tumor-organ
      contrast and therefore tumor detection. Specific uptake mechanisms also enable
      the assessment of organ function. Future design concepts of novel MR contrast
      agents may consider the desired uptake in specific cells or organs (ovaries,
      adrenal glands, lymph nodes etc.) with subsequent synthesis of appropriate
      carriers.

PMID- 8867434
TI  - [Semiquantitative detection of pain and heat sensations in evaluation of contrast
      media in pelvic/leg angiography. Intraindividual double-blind study with iomeprol
      350 and iopentol 350].
AB  - The effect on pain and heat sensation of monomere non-ionic contrast media with
      different osmolality was assessed in a randomized double-blind study. Peripheral
      angiography was performed in 29 patients who suffered from chronic occlusive
      vessel disease. The two non-ionic contrast media iomeprol and iopentol were
      applied intraindividually. The contrast media with an iodine concentration of 350
      mg/ml had an osmolality of 618 or 810 mosm/kg. A contrast medium volume of 80 or
      90 ml was injected in the abdominal aorta. The mean flow was 13.9 ml/s. The two
      contrast medium injections were separated by an interval of 10 min. No analgesic
      premedication was given. The pain and heat intensity was semiquantatively
      measured using a visual analogue scale ranging from 0 (no heat/pain) to 100
      (intractable heat/pain). The median after the first injection was calculated as
      40 for iomeprol and 70 for iopentol. The comparison of heat and pain sensations
      after the second injection showed a less distinct difference with a scale rating
      of 60 for iomeprol and of 65 for iopentol. The statistical variance was highly
      significant (p < 0.01) in favor of iomeprol.

PMID- 8867435
TI  - [Arrhythmia and dyspnea. Moderately differentiated leiomyosarcoma].

PMID- 8867436
TI  - [Product of the month: the Schering Atlas. Sectional anatomy of CT and MRI
      images].
AB  - The Schering Atlas is a teaching file in CT and MRI anatomy designed for
      physicians and students. It is available on CD-ROM, shows good image quality, and
      is easy to use in medium-price-range personal computer systems. Because of the
      amount and quality of image material, the Schering Atlas's price is appropriate
      for institutions, but not for private users.

PMID- 8867437
TI  - [Comments on the contribution by Ch. Marx et al. Tumorous space-occupying lesion
      of the os ilium].

PMID- 8867438
TI  - 31P NMR methods for the direct determination of ADP in the presence of ATP.
AB  - A new method is presented for the direct measurement of the amount of ADP in the
      presence of ATP by selectively eliminating the alpha- and gamma-ATP signals. The
      method is compared with other methods, both experimentally and theoretically,
      using the product-operator formalism. An analysis of the effect of beta 1
      inhomogeneity on the efficiency of the methods is also given. Experimental
      results obtained using adiabatic pulses to compensate for such effects are shown.
      The accuracy of this new method is demonstrated by measuring various ADP
      concentrations in a series of solutions containing ADP and ATP.

PMID- 8867439
TI  - Proton magnetic resonance and human thyroid neoplasia III. Ex vivo chemical-shift
      microimaging.
AB  - Magnetic-resonance chemical-shift microimaging, with a spatial resolution of 40 x
      40 microns, is a modality which can detect alterations to cellular chemistry and
      hence markers of pathological processes in human tissue ex vivo. This technique
      was used as a chemical microscope to assess follicular thyroid neoplasms, lesions
      which are unsatisfactorily investigated using standard histopathological
      techniques or water-based magnetic-resonance imaging. The chemical-shift images
      at the methyl frequency (0.9 ppm) identify chemical heterogeneity in follicular
      tumors which are histologically homogeneous. The observed changes to cellular
      chemistry, detectable in foci of approximately 100 cells or less, support the
      existence of a preinvasive state hitherto unidentified by current pathological
      techniques.

PMID- 8867440
TI  - Effectiveness and toxicity of several DTPA broadening agents for biological ESR
      spectroscopy.
AB  - The effectiveness of a standard ESR broadening agent, potassium
      trioxalatochromiate (CrOx), for use with the spin-label tempone, was compared to
      that of diethylenetriaminepentaacetic acid (DTPA) containing an ion (Gd, Cr, Mn,
      Fe) with a large magnetic moment. Signal attenuation, line broadening, toxicity,
      and cell membrane permeability were compared. As a broadening agent, CrOx was
      most effective, followed by Fe-DTPA. CrOx proved mildly toxic while Gd-DTPA and
      Fe-DTPA were virtually non-toxic. The human red blood cell membrane was tested
      for permeability to Fe- and Gd-DTPA and found to be impermeable to both. In
      situations where toxicity to cells is critical, the DTPA chelates, particularly
      Fe-DTPA, may prove an acceptable substitute for CrOx.

PMID- 8867441
TI  - Density-matrix calculations of the 1.5 T citrate signal acquired with volume
      localized STEAM sequences.
AB  - Citrate detection and quantitation with proton spectroscopic methods are of
      current interest as potential tools in the diagnosis and staging of prostate
      cancer. The stimulated echo acquisition mode (STEAM) sequence is a commonly used
      volume-localization method for detecting citrate signal. Since the 1H citrate
      resonance at clinically available field strengths arises from a strongly coupled
      two-spin system, the 90 degrees RF pulses and localizing gradients used in STEAM
      sequences result in a complicated dependence of signal intensity on timing
      intervals and gradient amplitudes. The density-matrix formalism has been applied
      to arrive at a general solution to this problem. Citrate-signal properties at 1.5
      T for different gradient localization schemes are examined with the solution.
      Optimal interpulse delays, deleterious gradient balances, zero-quantum
      oscillations with mixing time, and a low-frequency, large-amplitude oscillation
      with echo time are identified for signals acquired with the standard disposition
      of gradients in STEAM. The generality of the solution also allows for an
      examination of non-standard gradient disposition schemes for enhancing citrate
      signal and for quantifying the sensitivity of such approaches to both field
      inhomogeneities and off-resonance effects.

PMID- 8867442
TI  - The effects of cross-link density and chemical exchange on magnetization transfer
      in polyacrylamide gels.
AB  - The effects of polymer structure and water-macromolecule interactions on proton
      relaxation in an aqueous model polymer have been investigated using quantitative
      measurements of magnetization transfer. Polyacrylamide gels composed of 95%
      water, 5% comonomers acrylamide and N,N'-methylene-bis-acrylamide were studied.
      The structure and rigidity were varied by changing the cross-linking density of
      the polymer. The polymer showed a biphasic change in transverse relaxation with
      increasing cross-linking density which was accompanied by a sudden increase in
      magnetization transfer above 40% cross linking. This change may be attributed to
      the formation of rigid domains in the polymer which exhibit solid-like behavior
      with a short T2 (11 microseconds) and a Gaussian lineshape. Water-macromolecule
      interactions were controlled by varying the pH of the gel. At high pH (> 8),
      there was an increase in magnetization transfer and transverse relaxivity
      consistent with a chemical-exchange-mediated interaction between water protons
      and the polymer. By analyzing the system as two proton reservoirs coupled by
      magnetization exchange, the proton populations, intrinsic relaxation rates, and
      exchange rates were estimated, for different degrees of cross linking and pH.
      This model affords useful insights into the relevance of both supramolecular
      structure and chemical exchange on relaxation in tissues.

PMID- 8867443
TI  - Single-shot spectroscopic imaging (SISSI) using a PEEP/BURST hybrid.

PMID- 8867444
TI  - Effects of dipole-dipole interactions on microwave progressive power saturation
      of radicals in proteins.

PMID- 8867445
TI  - Selective transfer of magnetization by incoherent processes in nuclear magnetic
      resonance spectroscopy.

PMID- 8867446
TI  - The initiation of radiation damping by noise.

PMID- 8867447
TI  - Selective identification of threonine, valine, and isoleucine sequential
      connectivities with a TVI-CBCACONH experiment.

PMID- 8867448
TI  - Multisite band-selective decoupling in proteins.

PMID- 8867449
TI  - Monitoring NMR spectrometer performance during data accumulation for
      macromolecular structure determination.

PMID- 8867450
TI  - Application of genetic algorithms to spectral quantification.

PMID- 8867451
TI  - H NMR and electronic absorption spectroscopy of paramagnetic water-soluble meso
      tetraarylsubstituted cationic and anionic metalloporphyrins.
AB  - The ionization, mu-oxo-dimerization and axial ligation equilibria of free bases,
      iron(III) and manganese(III) derivatives of meso-tetrakis(p
      sulfonatophenyl)porphyrin (TPPS4) and meso-tetrakis(4-N-methyl
      pyridiniumyl)porphyrin (TMPyP) in aqueous solution are studied by 1H NMR and
      electronic absorption spectroscopy. At physiological pH, Fe(III) complexes of
      TMPyP and TPPS4 exist predominantly as dimers and may undergo transition to low
      spin species upon binding to biomolecules, whereas Mn(III) complexes are
      essentially monomeric. Dicyano and bis-imidazole complexes of FeTMPyP and FeTPPS4
      are low spin monomer adducts in the pH range 2.0 to 11.2. No low spin dimeric
      complexes were found. The low spin monocyano and high spin mono-imidazole
      complexes of FeTMPyP are formed in acidic and alkaline media, respectively. T1
      relaxation enhancement of water protons at 200 MHz induced by FeTPPS4 falls
      dramatically in the sequence high spin >> dimeric > low spin form.

PMID- 8867452
TI  - Release of CuPTSM from human serum albumin after addition of fatty acids.
AB  - Copper-62 labeled pyruvaldehyde bis (N4-methyl-thiosemicarbazonato) copper(II),
      CuPTSM, has been used to probe tissue perfusion by means of positron emission
      tomography. Despite promising results from animals, problems have been
      encountered in the use of 62CuPTSM to quantitate regional myocardial blood flow
      in humans. Ultrafiltration and plasma/erythrocyte partitioning studies with
      radiotracer have previously shown that CuPTSM is bound much more strongly by
      human serum albumin (HSA) than by dog serum albumin (DSA), limiting its ability
      to freely diffuse from blood into tissue. In this study, it is confirmed by
      electron spin resonance (ESR) that CuPTSM strongly binds to HSA with an apparent
      gparallel value of 2.12 and an apparent Aparallel value of 186 G. It is also
      shown that both spin-labeled stearic acid (5-SASL) and nonspin-labeled stearate
      inhibit CuPTSM binding to HSA. CuPTSM is completely released from HSA when the
      ratio of 5-SASL to HSA is 5:1. When pure sodium stearate is used, the binding of
      CuPTSM significantly decreased, about 73% of CuPTSM is released with a ratio of
      4:1 stearate to HSA. These results highlight a means of liberating CuPTSM from
      HSA.

PMID- 8867453
TI  - Cis-Dichloro(diaminosuccinate diethyl ester)palladium (II) as Pd(II)/Pt(II) model
      compound for DNA-binding and antitumor properties: solution equilibria of their
      aqua-, hydroxo-, and/or chloro-species.
AB  - Cis-Dichloro(diaminosuccinic acid)palladium(II), cis-[Pd(H2dasa)Cl2] (I), or cis
      dichloro(diaminosuccinate diethyl ester)palladium(II), cis-[Pd(Et2dasa)Cl2] (II)
      reacts with two equivalents of AgClO4 to give insoluble Pd(dasa) or an aqueous
      solution of [Pd(Et2dasa) (H2O)2](ClO4)2, respectively. Three solutions of this
      salt were titrated with NaOH (I = NaClO4 (0.15M),37 degrees C), and 133 E(H+)
      data (3.5 < or = pH < or = 7) were treated by SUPERQUAD to fit log beta pqr of
      cis-aquahydroxo-(pqr = 10-1, -5.25(3)) and di-mu-hydroxo-species (20-2, 
      6.55(1)). At pH > 7 the ester hydrolysis prevents the calculation of log beta 10
      2 for the cis-dihydroxo-complex. Another three solutions of such salt were
      titrated (I = 0.15M (NaClO4), 37 degrees C) with NaOH and NaCl simultaneously
      using two potentiometric systems (which measure H+ or Cl-). From 147 E(H+) and
      E(Cl-) data pairs and the above fixed log beta pqr, SUPERQUAD calculations yield
      log beta pqr for cis-chloro-aqua (pqr = 110, 3.65(1)), cis-chloro-hydroxo (11-1, 
      2.68 (4)), and cis-dichloro-species (120, 5.86(3)). Simulated and experimental
      titrations are in good agreement. Circular dichroism spectra of native DNA and
      drug:DNA complexes suggest that cis-Pd(H2dasa) and cis-Pd(Et2dasa) chelate
      moieties induce an opening and rotation of the stacked bases in the double helix.
      This finding is explained by the abundance of each one and of the total neutral
      and charged species of II in the tested CD solution.

PMID- 8867454
TI  - The uptake of Li+ into human 1321 N1 astrocytomas using 7Li NMR spectroscopy.
AB  - The uptake of Li+ ions into human 1321 N1 astrocytomas cultured on the surface of
      microcarrier beads was followed by 7Li NMR spectroscopy. The intracellular and
      extracellular 7Li resonances were separated by the use of dysprosium
      tripolyphosphate as a shift reagent. Excellent spectra were obtained from which
      the uptake of Li+ was found to be approximately ten times faster than that into
      human erythrocytes using the same technique and a steady-state intracellular Li+
      concentration was observed within 60 min. The low intracellular Li+ concentration
      attained, relative to the extracellular concentration, indicates the presence of
      an efflux mechanism in astrocytomas that actively transports Li+ against its
      concentration gradient. The intracellular volume was estimated by quantitative
      23Na NMR spectroscopy and the viability of the cells was confirmed by 31P NMR
      spectroscopy.

PMID- 8867455
TI  - A spectrophotometric study of the interaction of VO2+ with cytosine in
      nucleotides.
AB  - The interaction of VO2+ with cytidine-monophosphate, -diphosphate, and 
      triphosphate has been investigated at different pH values and metal-to-ligand
      ratios by differential UV-absorption spectroscopy. It is shown that at pH values
      between 3 and 5 and for metal-to-ligand ratios up to 0.5, the cytosine ring is
      involved in coordination. On the other hand, measurements performed at pH = 7
      show the absence of this type of interaction. Some comments on the possible
      structural characteristics of the generated complexes are made on the basis of
      the known coordination behavior of cytosine. Similar spectroscopic measurements
      with the systems VO2+/PO(3-)4, VO2+/P2O(4-)7, and VO2+/D-ribose were also
      performed in order to complement the analysis of the experimental results.

PMID- 8867456
TI  - Synthesis, characterization, and antitumor activity of a series of novel
      cisplatin analogs with cis-1,4-diaminocyclohexane as nonleaving amine group.
AB  - A series of novel platinum(II) complexes of the type PtII(cis-1,4-DACH)X (where
      cis-1,4-DACH = cis-1,4-diaminocyclohexane and X = dichloro, sulfato, oxalato,
      malonato, methylmalonato, tartronato, or 1,1-cyclobutanedicarboxylato [CBDCA)
      ligand and novel platinum(IV) complexes of the types PtIV(cis-1,4
      DACH)trans(Y)2Cl2 (where Y = chloro, hydroxo, acetato, propionato, or butyrato
      ligand) and PtIV(cis-1,4-DACH)trans(Cl)2(X) (where X = oxalato or CBDCA ligand)
      were synthesized and characterized by elemental analysis, infrared, and 195Pt NMR
      spectroscopic techniques. Platinum complexes had good in vitro cytotoxic activity
      against murine leukemia L1210/0 (IC50 = 0.0032-1.60 microM) and human ovarian
      A2780 (IC50 = 0.045-0.430 microM) cell lines.

PMID- 8867457
TI  - phi 20, a temperate bacteriophage isolated from Bacillus anthracis exists as a
      plasmidial prophage.
AB  - This study describes the isolation of temperate B. anthracis phages, from 4 out
      of 20 B. anthracis strains screened, by use of the inducing agents mitomycin C
      and UV light. Phage phi 20 isolated from B. anthracis Sterne 34F2 (pXO1+ pXO2-)
      was shown to have double-stranded DNA of size 48756 bp and a restriction site map
      showing nine sites for enzymes BamHI, BglII, and SstI is included. The phi 20
      genome was found to exist as a plasmidial prophage and the phage itself to have a
      polyhedral head of diameter 65 nm and tail 217 nm long and 15 nm wide.

PMID- 8867458
TI  - Effect of Staphylococcus epidermidis on hydrogel contact lens retention on the
      rabbit eye.
AB  - A slime-producing isolate of Staphylococcus epidermidis attached to FDA Group II
      hydrogel contact lenses persisted on rabbit eyes for up to 14 days, but except
      for minor redness of the eye no other effect was observed. Eye flora of eight
      representative New Zealand White rabbits included four different species of
      Staphylococcus including S. epidermidis and one species of Micrococcus, none of
      which produced overtly obvious biofilms. The slime-producing strain of S.
      epidermidis adhered more effectively to lenses than a non-slime-producing strain,
      and lenses challenged with the slime-producing strain remained on the rabbit eye
      for longer time periods than those with a non-slime-producing strain. Bacteria
      associated with the contact lens may affect the retention of the lens on the
      rabbit cornea during experimental studies.

PMID- 8867459
TI  - Evaluation of numerical analysis of random amplified polymorphic DNA (RAPD)-PCR
      as a method to differentiate Lactobacillus plantarum and Lactobacillus pentosus.
AB  - Lactobacillus plantarum and Lactobacillus pentosus grouped into one protein
      profile cluster at r > or = 0.70, separate from Lactobacillus casei,
      Lactobacillus sake, and Lactobacillus curvatus. Similar sugar fermentation
      reactions were recorded for representative strains of L. plantarum and L.
      pentosus. Representative strains, including the type of each species, were
      selected from the different protein profile clusters and their genetic
      relatedness determined by using numerical analysis of random amplified
      polymorphic DNA (RAPD)-PCR. The type strains of L. plantarum (ATCC 14917T) and L.
      pentosus (NCFB 363T) displayed different RAPD profiles and grouped into two
      independent clusters, well separated from L. casei, L. curvatus, and L. sake.
      Numerical analysis of RAPD-PCR proved a reliable and accurate method to
      distinguish between strains of L. plantarum and L. pentosus.

PMID- 8867460
TI  - Insecticidal activity of the protein encoded by the cryV gene of Bacillus
      thuringiensis kurstaki INA-02.
AB  - A new host specificity was discovered with the insecticidal protein encoded by
      the cryV gene. The cryV gene was cloned from the Bacillus thuringiensis kurstaki
      INA-02 strain, which was selected among a number of B. thuringiensis isolates
      because of its high activity against Spodoptera litura. Analyses by polymerase
      chain reaction (PCR) revealed that INA-02 contained the cryIA(a) and cryV genes.
      Since no Spodoptera activity was observed with B. thuringiensis sotto, which
      contained only cryIA(a), insecticidal activity of the protein encoded by the cryV
      gene was investigated with several insect species including S. litura. For
      bioassay, the cryV gene was highly expressed in an acrystalliferous B.
      thuringiensis strain, BT51. The CryV protein from BT51 was assayed against larvae
      of three lepidopteran species, Bombyx mori, S. litura, and Plutella xylostella.
      The protein was highly active against S. litura and P. xylostella, suggestive
      that the protein contributes to the unique activity of INA-02.

PMID- 8867461
TI  - Staphylococci bind heparin-binding host growth factors.
AB  - Staphylococcus aureus, which mediated binding to heparan sulfate, and also
      strains of coagulase-negative staphylococci (CNS) adhered in high numbers to
      polymers with end-point attached heparin. A characteristic feature of several
      cell growth factors is strong affinity for heparin. In the present study, binding
      of the 125I-labeled heparin-binding growth factors (HBGF), acidic and basic
      fibroblast growth factor (aFGF, bFGF), and platelet-derived growth factor (PDGF)
      by S. aureus and CNS strains was examined. Staphylococcal strains used in this
      study bind bFGF and PDGF, but not aFGF. The binding of bFGF and PDGF was time
      dependent, influenced by pH and ionic strength for S. aureus Cowan 1.
      Preincubation of staphylococcal cells with unlabeled bFGF enhanced bFGF binding,
      but heparin, protamine sulfate, poly-L-lysine, and suramin were potent inhibitors
      of 125I-bFGF binding to cells of S. aureus Cowan 1. Glycosaminoglycans of
      comparable size (chondroitin sulfate), other polysulfated polymers (lambda
      carrageenan, fucoidan), and some polysulfated polysaccharides (dextran sulfate,
      pentosan polysulfate) inhibited binding of both GFs to various extents. The
      partial inhibition of binding of both GFs after protease and periodate treatments
      indicates that both proteinaceous and other carbohydrate moieties participate in
      the binding. A lysozyme cell surface extract and bacterial lysates of S. aureus
      Cowan 1 competitively inhibited binding of 125I-bFGF and 125I-PDGF. These results
      suggest that staphylococci have the ability to bind two of the HBGFs, bFGF and
      PDGF, but not aFGF, via more than one cell structure. These binding structures
      seem to be exposed on the cell surface and deeply anchored in the cytoplasmic
      membrane as well.

PMID- 8867462
TI  - Inducer expulsion is not a determinant of diauxic growth in Streptococcus bovis.
AB  - When Streptococcus bovis JB1 was repeatedly transferred in a medium that
      contained the non-metabolizable glucose analog, 2-deoxyglucose, it lost its
      phosphotransferase system (PTS) for glucose but was still able to take up glucose
      via a facilitated diffusion mechanism. The wild type (JB1) had an inducible
      enzyme II lactose, but the mutant (JB1(2DG)) had a constitutive lactose PTS.
      JB1(2DG) was no longer able to exclude lactose when it was provided with glucose,
      but it retained its ability to expel a non-metabolizable lactose analog. Because
      JB1(2DG) could utilize glucose and lactose simultaneously and grow in a non
      diauxic fashion, it appeared that inducer expulsion was not an important
      catabolite regulatory mechanism. Based on these results, inducer expulsion may be
      an artifact of non-metabolizable sugars.

PMID- 8867463
TI  - The ability of a recombinant Escherichia coli strain to synthesize 2-C-methyl-D
      erythritol-2,4-cyclopyrophosphate correlates with its tolerance to in vitro
      induced oxidative stress and to the bactericidal action of murine peritoneal
      macrophages.
AB  - A number of bacteria are able to synthesize 2-C-methyl-D-erythritol-2,4
      cyclopyrophosphate (BOSS) in response to oxidative stress. Here we show that the
      ability to synthesize BOSS can be genetically transferred from Corynebacterium
      ammoniagenes to Escherichia coli. A total DNA library from C. ammoniagenes ATCC
      6872 established in the pBluescript SKII+vector backbone was transfected into E.
      coli XL-1 blue. Recombinant clone 2-31, which was resistant to redox-cycling
      agents, was selected. NMR studies showed that this clone was able to synthesize
      BOSS. We also studied the resistance of clone 2-31 to the bactericidal action of
      macrophages. Clone 2-31 cells had better survival within murine peritoneal
      macrophages than parental E. coli XL-1-blue cells. Since the ability to
      synthesize BOSS correlates with increased survival of bacteria within
      macrophages, we suggest that the pathogenicity of Corynebacteria could be
      mediated through the synthesis of BOSS.

PMID- 8867464
TI  - Virulence of Vibrio alginolyticus isolated from diseased tiger prawn, Penaeus
      monodon.
AB  - Outbreaks of mass mortality among cultured tiger prawns (Penaeus monodon) with
      white spotted syndrome (WSS) in the carapace occurred in the summer of 1994 in I
      Lan, Taiwan. A swarming strain Val was isolated from hemolymph of the moribund
      prawns with tryptic soy agar (TSA, supplemented with 1% NaCl, Oxoid) and/or
      thiosulfate citrate bile salt sucrose (TCBS, Difco) agar. This strain was
      characterized and identified to be Vibrio alginolyticus. The strain was
      susceptible to antibiotics such as chloramphenicol, ciprofloxacin, doxycycline
      hydrochloride, nalidixic acid, oxolic acid, and oxytetracycline while resistant
      to ampicillin, novobiocin, penicillin G, sulfisoxazole, and sulfonamide. The
      bacteria and their extracellular products (ECP) were lethal to both tiger prawns
      (P. monodon) and kuruma prawns (P. japonicus) with LD50 values of 1.13 x 10(5),
      2.46 x 10(5) CFU/g, and 0.23, 0.63 micrograms protein/g prawn body weight,
      respectively.

PMID- 8867465
TI  - Molecular characterization of the xerC gene of Lactobacillus leichmannii encoding
      a site-specific recombinase and two adjacent heat shock genes.
AB  - Sequencing of four overlapping DNA fragments comprising 3.527 kb isolated from a
      L. leichmannii genomic library revealed three complete open reading frames (ORFs)
      and one that was truncated. The deduced amino acid sequences of the complete ORFs
      showed considerable similarities with the already known sequences of the xerC,
      hslV, and hslU gene products of Escherichia coli: the site-specific XerC
      recombinase, a member of the lambda integrase family, and the HtpI resp. HtpO
      heat shock proteins. The deduced amino acid sequence of the fourth, incomplete
      ORF upstream the xerC gene showed strong homology with the gid A gene product of
      B. subtilis.

PMID- 8867466
TI  - Recurrent inhibition and clustered connectivity as a basis for Gabor-like
      receptive fields in the visual cortex.
AB  - A continuous-space model of visual cortex interactions which, starting from
      elongate Gaussian functions, leads to high-selective Gabor-like receptive fields,
      is proposed. The model is based on intracortical inhibition mechanisms occurring
      through medium-range clustered connections. The analysis, carried out under the
      assumption of a linear superposition of geniculate and intracortical
      contributions, shows how inhibition enhances both spatial and spatial-frequency
      selectivity. The effects of inhibition strength and of its spatial organization
      on the properties of the resulting receptive field are investigated.
      Specifically, the relationships between receptive fields and inhibition schemes
      are investigated by deriving analytical expressions for their dependence and
      through a systematic numerical parametric study. The emergence of periodic
      receptive fields, like the ones observed in neurophysiological measurements, is
      also pointed out in relation to the clustered nature of the inhibitory scheme.

PMID- 8867467
TI  - Synchronization without oscillatory neurons.
AB  - Experimental results suggest that neurons in the cortex synchronize their action
      potentials on the millisecond time scale. More importantly this binding expresses
      functional relationships between the neurons. A model of neuronal interactions is
      proposed in which simultaneous discharges of neurons develop through specialized
      synaptic circuits. As an important prerequisite for this synchronization it is
      demonstrated that SynFire chains, generating different levels of excitation,
      propagate their activity waves at distinct velocities. Two chains were coupled by
      excitatory synapses and their activity was initiated at different times. Due to
      synaptic interactions, activity in the earlier-initiated chain accelerates
      propagation in the other chain until the two activity waves are synchronized.
      Compared with several neural network models with oscillatory units,
      physiologically more plausible neurons are simulated. It is still under debate
      whether neurons in the cortex show oscillatory discharges per se. In particular,
      a high rate of noise relative to very weak synaptic gains cannot impair our
      results in the neural network simulations.

PMID- 8867468
TI  - Thermoregulation in homeotherms: central temperature results from optimization of
      energy transfers.
AB  - In contrast to the classical homeostatic concept of the constancy of the central
      temperature, this study proposes an original model of thermoregulation based on
      the optimization of energy transfers. Exchange of the energy consumed or produced
      by the cell between the cell and the external medium has an associated energy
      cost. The different variables of the internal medium-flows, pressures,
      concentrations and also temperatures, since heat is but a particular form of
      energy--are continuously set at optimal values such that this cost is always
      minimal for the prevailing constraints with which the organism is faced. The
      proposed thermoregulatory model accounts for the physiological spatial and
      temporal variability of the body's temperatures. The predictive curves suggest a
      new approach to experimental studies concerned with thermal regulation and throw
      new light on their results.

PMID- 8867469
TI  - Extracellular action potentials of skeletal muscle fibre affected by 4
      aminopyridine: a model study.
AB  - A new specially designed analytical function approximating the intracellular
      action potentials (ICAPs) for calculation of the extracellular potentials (ECAPs)
      at various radial and axial distances from the active fibre is proposed. 4
      Aminopyridine (4-AP) was used to obtain ICAPs with a prolonged repolarization
      phase in order to investigate the influence of changes in ICAP shape on the
      ECAPs. From the experimentally recorded ICAPs before and after treatment of frog
      skeletal muscle fibres with 4-AP, approximated by the new function, the ECAPs
      were calculated applying the line-source model in a finite fibre. Using this
      function allowed calculation of the ECAPs at distances not accessible for the
      experimental recordings. The total ionic current (Ii) during the action potential
      was calculated using the cable equation. Our results showed that the ratio of the
      first positive to the negative phases of the ECAPs of treated fibres increased at
      large radial distances (3000 microns and more) and the terminal positive phase
      was asymmetric with an abrupt initial deflection followed by a slow inverse
      deflection. The calculated ECAPs at various axial distances from the fibre end
      (cylindrical and conical part) and at radial distances from the fibre membrane
      ranging from 0 to 5000 microns, corresponded in shape to the experimentally
      recorded potentials of untreated and 4-AP-treated muscle fibres.

PMID- 8867470
TI  - Structural study of the development of ocularity domains using a neural network
      model.
AB  - We present a model for the development of ocularity domains in the visual cortex
      of mammals during the embryonic stage. We model the thalamo-cortical pathway with
      a self-organising neural network with two source layers, each of them serving
      different retinae, and one target layer, where the connections end. The
      connectivity between the source layers and the target layer is driven by Hebbian
      learning. In both the source layers and the target layer we assume excitatory
      lateral signal diffusion between proximal neurons that causes them to be
      correlated. According to the developmental state being modelled, we do not
      consider either correlation or anti-correlation between the signals originated in
      neurons of different retinae. The basic assumptions made are proved to be
      sufficient to attain a distribution of connections arranged in ocularity domains.
      The dependence of the geometry of the ocularity domains on the parameters of the
      model is analysed and a correlation between the width of the signal diffusion and
      the extent of the domains is found. The generality of the assumptions made allows
      an easy translation of the model to explain the development of other elements of
      the sensory nervous system.

PMID- 8867471
TI  - Modeling motor cortical operations by an attractor network of stochastic neurons.
AB  - Understanding the neural computations performed by the motor cortex requires
      biologically plausible models that account for cell discharge patterns revealed
      by neurophysiological recordings. In the present study the motor cortical
      activity underlying movement generation is modeled as the dynamic evolution of a
      large fully recurrent network of stochastic spiking neurons with noise
      superimposed on the synaptic transmission. We show that neural representations of
      the learned movement trajectories can be stored in the connectivity matrix in
      such a way that, when activated, a particular trajectory evolves in time as a
      dynamic attractor of the system while individual neurons fire irregularly with
      large variability in their interspike intervals. Moreover, the encoding of
      trajectories as attractors ensures high stability of the ensemble dynamics in the
      presence of synaptic noise. In agreement with neurophysiological findings, the
      suggested model can provide a wide repertoire of specific motor behaviors,
      whereas the number of specialized cells and specific connections may be
      negligibly small if compared with the whole population engaged in trajectory
      retrieving. To examine the applicability of the model we study quantitatively the
      relationship between local geometrical and kinematic characteristics of the
      trajectories generated by the network. The relationship obtained as a result of
      simulations is close to the '2/3 power law' established by psychophysical and
      neurophysiological studies.

PMID- 8867472
TI  - Coupled oscillators utilised as gait rhythm generators of a two-legged walking
      machine.
AB  - The gait of current two-legged walking machines differs from that of humans,
      although the kinematic structures of these machines' legs frequently imitate
      human limbs. This paper presents a method of generating the trajectories of hip
      and knee joint angles resulting in a gait pattern similar to that of a human. For
      this purpose the solutions of coupled van der Pol oscillator equations are
      utilised. There is much evidence that these equations can be treated as a good
      model of the central pattern generator generating functional (also locomotional)
      rhythms in living creatures. The oscillator equations are solved by numerical
      integration. The method of changing the type of gait by changing appropriate
      parameter values in the oscillator equations is presented (change of velocity and
      trajectory of leg-ends). The results obtained enable enhanced control of two
      legged walking systems by including gait pattern generators which will assume a
      similar role to that of biological generators.

PMID- 8867473
TI  - A columnar model of somatosensory reorganizational plasticity based on Hebbian
      and non-Hebbian learning rules.
AB  - Topographical and functional aspects of neuronal plasticity were studied in the
      primary somatosensory cortex of adult rats in acute electrophysiological
      experiments. Under these experimental conditions, we observed short-term
      reversible reorganization induced by intracortical microstimulation or by an
      associative pairing of peripheral tactile stimulation. Both types of stimulation
      generate large-scale and reversible changes of the representational topography
      and of single cell functional properties. We present a model to simulate the
      spatial and functional reorganizational aspects of this type of short-term and
      reversible plasticity. The columnar structure of the network architecture is
      described and discussed from a biological point of view. The simulated
      architecture contains three main levels of information processing. The first one
      is a sensor array corresponding to the sensory surface of the hind paw. The
      second level, a pre-cortical relay cell array, represents the thalamo-cortical
      projection with different levels of excitatory and inhibitory relay cells and
      inhibitory nuclei. The array of cortical columns, the third level, represents
      stellate, double bouquet, basket and pyramidal cell interactions. The dynamics of
      the network are ruled by two integro-differential equations of the lateral
      inhibition type. In order to implement neuronal plasticity, synaptic weight
      parameters in those equations are variables. The learning rules are motivated by
      the original concept of Hebb, but include a combination of both Hebbian and non
      Hebbian rules, which modifies different intra- and inter-columnar interactions.
      We discuss the implications of neuronal plasticity from a behavioral point of
      view in terms of information processing and computational resources.

PMID- 8867474
TI  - [After care of breast carcinoma patients--recommendations from the Berlin
      consensus conference].

PMID- 8867475
TI  - [Menopausal symptoms in breast carcinoma patients. Is effective treatment
      possible?].
AB  - Vasomotor complaints occuring during the menopause need treatment, and this also
      applies to patients with cancer, whose quality of life, already reduced by the
      disease, its treatment and sequelae of therapy, would otherwise decline further.
      While estrogen replacement therapy is employed to treat climacteric symptoms, the
      fact that estrogens may stimulate the growth of the mammary carcinoma cells would
      appear to rule out estrogen replacement in patients with breast cancer. Against
      this background, a stepped treatment plan is recommended, in which the initial
      application of symptomatic measures/placebos is followed by non-hormonal drugs
      and, finally, hormones. Should the results obtained be inadequate, and distress
      causing symptoms persist, estrogen replacement treatment aimed at improving
      quality of life may be employed as a last resort, after a careful weighing up of
      the risks and establishment of an "informed consensus".

PMID- 8867476
TI  - [Diagnosis and evaluation of climacteric symptoms. The "Menopause Rating Scale"
      MRS helps in diagnosis and evaluation of therapeutic effectiveness].
AB  - For the evaluation of climacteric symptoms, Kupperman and his collaborators
      worked out guidelines as long ago as 1953. As time passed, however, their
      validity was increasingly called into question. In the nineteen-seventies, on the
      basis of large epidemiological studies, the conclusion was drawn that merely the
      symptoms hot flushes and vaginal atrophy were specific to the menopause, while
      other, largely psychological, complaints represented a "domino effect", so to
      speak. In contrast to this, the scale (Menopause Rating Scale [MRS]) presented
      here also permits the identification of emotional complaints. In addition,
      urinary tract problems, joint and muscle pain, and sexual disorders are also
      rated. For each of the ten symptom groups, a graphical rating scale ranging from
      0.0 (no symptoms) to 1.0 (severe symptoms) is available that permits a synoptic
      individual complaints profile of the patient to be established.

PMID- 8867477
TI  - [Lambliasis--a treatment responsive complication of Crohn disease].

PMID- 8867478
TI  - [Ciprofloxacin in treatment of common bacterial skin infections. Results of an
      open study in general practice].

PMID- 8867479
TI  - [After care of breast cancer: tips for medical charges].

PMID- 8867480
TI  - Imaging of atherosclerosis (Part I).
AB  - Atherosclerosis is the leading cause of morbidity and mortality in the Western
      World. Standard imaging techniques such as angiography, ultrasonography and
      computed tomography are still not effective in detecting atheromatous plaques in
      their early stages of development, when the lesions are most metabolically active
      and therapeutic interventions could beneficial. These techniques identify
      morphological changes such as increased wall thickness, decreased luminal
      diameter or related haemodynamic changes such as turbulence of blood flow.
      Unfortunately, all these phenomena occur when the plaque has evolved and
      encroaches on the lumen. There is a need for non-invasive methods that could
      assess the presence and the extension of atherosclerotic disease in its early
      stages, when the lesions are in their metabolically most active stage but still
      do not narrow the diameter of the lumen. Part I of this article presents an
      overview of the diagnostic procedures angiography, sonography, computed
      tomography and magnetic resonance tomography in imaging atherosclerotic lesions.
      Part II will concentrate on the diagnostic possibilities of scintigraphic imaging
      and positron emission tomography.

PMID- 8867481
TI  - [Amalgam allergy--diagnosis and consequences].
AB  - Allergy to dental amalgam is rare--in contrast to Press reports and public
      opinion. Whereas sensitivity to one or more mercury salts is quite frequently
      detected in the patch test, it is seldom of clinical relevance. In this report we
      define the limited indications for performing an allergy test, describe the exact
      test criteria and delineate the consequences of a positive test result. A
      critical appraisal of the result is essential in order to avoid unnecessary
      procedures which are expensive and far from being effective, may even be
      potentially dangerous.

PMID- 8867482
TI  - [Clinical relevance of changes in serum prolactin level caused by
      electroconvulsive therapy].
AB  - In this study 15 (4 males, 11 females) depressive patients (according to DSM-III
      R criteria), who were refractory to psychopharmacological treatment were referred
      for electroconvulsive therapy (ECT). Six ECTs were administered within a period
      of 3 weeks. Before the first, third and fifth ECT and 15, 30, and 60 minutes
      after each of these 3 treatments serum levels of prolactin were determined. After
      six ECTs eight patients showed significant symptomatic improvement, whilst the
      depressive symptoms in the other seven patients remained more or less unchanged.
      There was no statistically significant difference with respect to prolactin
      response following the three ECTs between the symptomatically improved and the
      unchanged group. There was no correlation of severity of depression and prolactin
      baseline levels before the first ECT. Neither baseline prolactin levels prior to
      the first ECT nor prolactin response predicted therapeutic outcome. From this
      point of view changes in serum prolactin levels do not reflect therapeutic
      pathways in depression or mechanisms of action of ECT.

PMID- 8867483
TI  - [Comparison of thrombosis rate after laparoscopic and conventional interventions
      with the I(125) fibrinogen test].
AB  - The purpose of the present work was to compare the frequency of thrombosis in
      patients after laparoscopic and conventional operations. The diagnosis of
      thrombotic complications of the veins of the legs was determined by means of the
      I125 fibrinogen test. This isotopic test was chosen because it enables the early
      diagnosis of a thrombosis of the venous sinus of the calf at a stage at which no
      clinical symptoms have yet appeared. It was shown that in the group of patients
      submitted to laparoscopic intervention only 19 (18.8%) developed thrombotic
      complications out of the 101 patients, whereas in the group of conventionally
      operated patients 42 cases (45.7%) occurred in the 92 patients. Moreover, there
      was a statistically significant difference in the incidence of thrombotic
      complications in patients after laparoscopic cholecystectomy in comparison with
      the traditional operative method, with 14 cases (23.3%) out of 60 patients versus
      35 (62.5%) out of 56 patients, respectively.

PMID- 8867484
TI  - Treatment with L-arginine is likely to stimulate generation of nitric oxide in
      patients with peripheral arterial obstructive disease.
AB  - The impairment of endothelial function in hypercholesterolaemic animals and
      humans is known to be reversed by intravenous infusions of L-arginine (L-ARG),
      the precursor of NO. 22 patients with peripheral arterial obstructive disease
      (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three
      hours, daily for seven consecutive days. This treatment resulted in elongation of
      the painfree and maximum walking distances, as well as shortening of the period
      of time required for pain relief after walking the maximum distance. A rise in
      the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial
      blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the
      ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG
      the spontaneous (PAR) as well as the ADP- and collagen-induced platelet
      aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened,
      plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels
      increased. These data indicate beneficial effects of L-ARG as a therapeutic agent
      in patients with PAOD. We presume that in these patients high doses of exogenous
      L-ARG can be partially converted to NO.

PMID- 8867485
TI  - [A case of cystic duplication of the stomach].
AB  - The case is presented of a 25 year-old female patient with a gastric duplication
      cyst. There are only few reports in the literature of this rare malformation. The
      unspecific symptoms make diagnosis of this condition difficult. It is possible
      that, in future, due to the advances in visual diagnostic methods (ultrasound,
      endoscopy and computed tomography) this anomaly will be recognized more
      frequently and the case reports published extensively.

PMID- 8867487
TI  - An exploratory study of the pattern of consent for autopsy in a regional hospital
      setting.
AB  - A prospective study of the pattern of responses to requests for autopsy in a
      general surgical unit was performed. Information on the characteristics of the
      deceased, of the requestee and of the requester was documented in the case of 66
      patients who died while in hospital. Permission to perform autopsy was not
      requested in 39 out of 66 cases and this was the most frequent contributory
      factor to the low rate of autopsy. Once a decision to grant or refuse autopsy is
      made by relatives of the deceased, the decision is unlikely to be reversed.
      Permission to perform autopsy was more likely to be sought when the deceased was
      male than when deceased was female. The relatives of patients who had recently
      undergone surgery were more likely to refuse permission for autopsy than were
      those of patients who had not had recent surgery.

PMID- 8867486
TI  - Pain relief following cardiac surgery: a review.

PMID- 8867488
TI  - Radiographic assessment of acetabular prosthesis anteversion: an experimental
      study.
AB  - Two trigonometric methods used to assess acetabular cup orientation
      radiographically derive the angle of anteversion differently and yielded
      statistically significantly different results when compared using a laboratory
      model of the pelvis. The need for standardisation is suggested.

PMID- 8867489
TI  - Sports injuries in school gaelic football: a study over one season.
AB  - School football injuries were studied over the seven months of one season on 150
      males aged 16.94 +/- 0.82 years. Training averaged 4.13 +/- 1.47 hours per week
      and matches 1.84 +/- 0.60 hours per week. Mean time injured was: 0.51 +/- 1.7
      days in hospital, 34.27 +/- 37.08 days off sport and 13.98 +/- 5.22 days of
      restricted activity. There were 136 match and 63 training injuries giving 175.98
      injuries per 10000 hours of matches and 31.06 injuries per 10000 hours of
      training. Injuries were treated as follows: hospital 83, general practitioners
      51, physiotherapists 28, no treatment 38. The most common injuries were: ankle
      sprain (11.6% of the total), hamstring strain (6.5%), contusion (6.5%) back
      strain (6%) knee sprain (5.0%), finger sprain (5.0%), other muscle strains
      (5.0%), fracture of the wrist (5.0%), dislocation of the finger (4.5%), overuse
      injury of the back (4.0%), tenosynovitis (3.5%), fracture of the ankle (3.0%).
      Thirteen injuries were to goal-keepers, 85 to backs, 31 to mid-field players and
      70 to forwards. In 34.83% of the injuries foul play was given as the major cause.
      This was followed by "Lack of fitness", "Poor kit or boots" and "Previous injury"
      (all 11.24%). The most common minor cause was "Poor state of the pitch" (17.42%
      of injuries).

PMID- 8867490
TI  - One stage surgical management of deep infection of total hip arthroplasty.
AB  - Nineteen patients underwent one stage surgical management of infected hip
      prostheses over a five year period. Thirteen were male and six were female. The
      mean age was 64 years (Range 49-82). The mean time interval between primary and
      revision surgery was 26 months (Range 6 months-16 years). One stage re
      implantation was performed in 15 patients and excision arthroplasty in 4
      patients. The mean duration of follow up was 4 years, 5 months (Range 2-7 years).
      Patients were assessed, radiologically and clinically using the Harris hip score.
      Staph. aureus(7) and Slaph. epidermidis(10) were the most frequent organisms
      isolated. Patients who underwent excision arthroplasty had discharging sinuses,
      extensive soft tissue and bone involvement or were poor anaesthetic candidates.
      Three of these patients had a poor outcome in terms of pain function and
      deformity. Five of the patients who underwent one stage re-implantation had an
      excellent clinical result, seven had a good result, one had a fair result and one
      a poor result. There was no recurrence of infection in either group of patients.
      One stage re-implantation can result in a good clinical outcome and eradication
      of infection. Resection arthroplasty is a necessary option in a minority of
      patients, however, while successful in eradicating infection may result in a poor
      functional outcome.

PMID- 8867491
TI  - The osteogenic potential of extracorporeal shock wave therapy. an in-vivo study.
AB  - We studied the effects of extracorporeal shock wave therapy (ESWT) on the healing
      potential of osteotomies in rabbit radii. The results of sequential low dose
      shock wave therapy were compared prospectively with natural healing in the radii
      of New Zealand white rabbits. Our results suggest that ESWT causes new bone
      formation locally. However such exuberant callus formation does not equate with
      accelerated fracture healing and in fact implies a delay in the remodelling
      process.

PMID- 8867492
TI  - A no-touch technique of loading bone cement for gun injection at total hip
      arthroplasty.
AB  - Cement guns are widely used to introduce bone cement into the proximal femur at
      total hip arthroplasty. Loading these devices is cumbersome. A convenient
      technique for filling cement gun inserts is described.

PMID- 8867493
TI  - First isolation and characterisation of Borrelia garinii, agent of Lyme
      borreliosis, from Irish ticks.
AB  - Nymphal Ixodes ricinus, the tick vector of Lyme borreliosis, were collected from
      the edges of paths in Muckross Demesne, Killarney National Park, Co. Kerry,
      Ireland. Examination of some of these nymphs by indirect immunofluorescence
      showed an infection prevalence of 12% with Borrelia burgdorferi sensu lato, the
      spirochaete agent of Lyme borreliosis. Gerbils (Meriones unguiculatus) were
      infected by infesting them with other nymphs from the same batch. Subsequently
      uninfected laboratory larvae were applied to the gerbils and the contents of the
      resulting infected engorged ticks were then placed in media and the spirochaetes
      cultured. The spirochaetes were identified as B. burgdorferi sensu lato by
      indirect immunofluorescence using monoclonal antibodies and they were further
      characterised by polymerase chain reaction and pulsed-field gel electrophoresis.
      Both of these latter techniques showed that spirochaetes in all samples belonged
      to the genomic species, Borrelia garinii.

PMID- 8867494
TI  - High resolution computed tomography in cystic fibrosis: correlation with
      pulmonary function and assessment of prognostic value.
AB  - OBJECTIVE: To assess the correlation between HRCT and pulmonary function in
      patients with CF. Further, to assess the prognostic value of HRCT in these
      patients. SUBJECTS AND METHODS: Clinical examination, chest radiographs and HRCT
      scans on 30 CF patients with an average age of 17 were scored using established
      scoring systems. The results were correlated with FEV1 and FVC both at time of CT
      scanning and after 30 months. Results were also correlated with the clinical
      progress of the patients over the follow-up period. RESULTS: HRCT, chest
      radiograph and clinical examination demonstrated similar correlation (p < 0.001)
      with FEV1 and FVC at the time of scanning. HRCT demonstrated the closest
      correlation with the clinical progress of the patients over the follow-up period
      and with follow-up pulmonary function. A maximum combined score for
      bronchiectasis and emphysema on HRCT seemed to indicate a poor prognosis.
      CONCLUSION: HRCT in CF patients correlates well with pulmonary function at time
      of scanning and at follow-up, and with clinical progress. There may be a role for
      CT in the identification of adolescent/adult patients who can be expected to need
      aggressive therapy in the future.

PMID- 8867495
TI  - Open common bile duct exploration--end of an epoch?
AB  - With the advent of laparoscopic cholecystectomy and the impending replacement of
      open common bile duct exploration, we have reviewed our ten year experience of
      conventional common bile duct exploration. Open cholecystectomy was performed in
      1681 patients and the common bile duct was explored in 325 (19%). Following
      initial duct exploration, rigid choledo identified residual choledocholithiasis
      in 58 and periampullary neoplasia in 2 patients. Unexpected retained stones were
      identified in 3 patients (0.9%). In a further 4 patients, stones which could not
      be dislodged from the hepatic ducts were confirmed on 10 day T-tube cholangiogram
      -transduodenal sphincteroplasty had been performed at the time of original
      surgery in all four. The mortality was 1.9% overall and 1% during the last 5
      years. Endoscopic exploration must compare favourably with these data for safe
      transition to less invasive techniques.

PMID- 8867496
TI  - Is the fertile period reduced in patients with inflammatory bowel disease?

PMID- 8867497
TI  - Enhanced T-helper 2 lymphocyte responses: immune mechanism of Helicobacter pylori
      infection.
AB  - Several lines of evidence implicate Helicobacter pylori (H. pylori) infection in
      gastroduodenal inflammation. However, the exact pathogenesis of H. pylori
      infection is not fully understood. T-helper (TH) lymphocytes may be subdivided
      into TH1 and TH2 cells based on the distinct patterns of cytokine production. TH1
      reaction is associated with immunity or resistance to infection, while TH2
      reaction is associated with the progression or persistence of infection. The
      production of interferon-gamma (INF-gamma) and interleukin 2 (IL-2), which are
      type 1 cytokines, is decreased in H. pylori infection. Enhanced production of
      type 2 cytokines (IL-4) and IL-6) is observed in individuals with H. pylori
      infection. Suppressed proliferative responses of peripheral blood and gastric
      lymphocytes have also been demonstrated in patients with H. pylori colonisation,
      suggesting that specific T-cell responses may be down-regulated by an enhanced
      TH2 reaction. Suppressed TH1 and enhanced TH2 responses in H. pylori infection
      may be involved in the immunopathogenesis of chronic H. pylori infection.

PMID- 8867498
TI  - Staphylococcus aureus sensitivity to various antibiotics--a national survey in
      Ireland 1993.
AB  - The sensitivity of Staphylococcus aureus (S. aureus) to methicillin, penicillin,
      gentamicin, erythromycin, ciprofloxacin, fusidic acid and mupirocin was tested in
      1152 clinical isolates from nine hospital microbiology departments. In all cases
      standard methods for culture and sensitivity were employed using either the
      Stokes' or a modified Stokes' method for susceptibility testing. The isolates
      were recovered from 1150 patients (606 men, 544 women; mean age: 41 years) and
      only those deemed relevant to the patient's clinical condition were included. Of
      the total 1152 isolates, 454 were regarded as hospital acquired, 506 were
      community acquired and the source of the remaining 192 isolates was unknown. The
      overall percentages of S. aureus sensitive to the tested antibiotics were as
      follows: methicillin 85%, penicillin 8%, gentamicin 89%, ciprofloxacin 85%,
      erythromycin 80%, fusidic acid 96%, mupirocin 98%. The sensitivity of the
      methicillin resistant strains to the other antibiotics tested was generally low
      except for fusidic acid and mupirocin, both of which retain good activity against
      methicillin resistant S. aureus (MRSA).

PMID- 8867499
TI  - DNA amplification fingerprinting (DAF) applied to the investigation of
      Acinetobacter baumanii isolated from intensive care unit patients.
AB  - Acinetobacter are important emerging nosocomial pathogens. In this paper thirteen
      Acinetobacter baumanii from intensive care patients were isolated. These were
      initially typed using the API-20 NE biotyping system and antibiogram analysis.
      Results obtained using these methods failed to convincingly characterise the
      organisms. In this report a method to characterise these Acinetobacter baumanii
      isolates is described, which utilises a modified polymerase chain reaction (PCR),
      capable of generating genomic fingerprints, known as DNA amplification
      fingerprinting (DAF). Purified chromosomal DNA of cultured clinical isolates of
      Acinetobacter baumanii were subjected to DAF using the M13 universal sequencing
      primer. Polymorphic DNA bands produced, were visualised after agarose gel
      electrophoresis and ethidium bromide staining. Results demonstrated that six of
      the thirteen clinical isolates represented one group and a second group of two
      isolates displayed identical fingerprint patterns. The remaining four organisms
      were all unique. This genotype based method is rapid, simple, reproducible and
      may have potential as a means of specifically typing Acinetobacter spp. allowing
      the route(s) of nosocomial transmission to be identified and to assess the
      efficiency of instituted infection control measures.

PMID- 8867500
TI  - Laparoscopic diagnosis and resection of a bleeding Meckel's diverticulum in a
      thirteen year old female.
AB  - Laparoscopy has been described as being safe and effective in the diagnosis and
      treatment of Meckel's Diverticulum. We describe the use of laparoscopy in the
      diagnosis and resection of a Meckel's diverticulum in a 13 year old girl.

PMID- 8867501
TI  - Synchronous metastatic breast cancer in a husband and wife.
AB  - We present the first reported case of synchronous metastatic breast carcinoma in
      a husband and wife.

PMID- 8867502
TI  - Colovesical fistula caused by chronic chicken bone perforation.
AB  - We report a case of colovesical fistula caused by chronic perforation of sigmoid
      colon diverticulum due to a swallowed chicken bone. This appears to be the fifth
      case of its kind ever reported in the literature.

PMID- 8867503
TI  - Surgical scar endometriosis.

PMID- 8867504
TI  - Two atypical presentations of giant cell arteries.

PMID- 8867505
TI  - Giant phaeochromocytoma: case report.
AB  - A case of giant phaeochromocytoma occurring in a 47-year-old man with no signs or
      symptoms of catecholamine secretion is reported. Abdominal ultrasound scanning,
      chest X-ray, computed tomography and magnetic resonance imaging were
      preoperatively performed. The patient was operated through a thoracoabdominal
      incision and section of the left hemidiaphragm. The giant retroperitoneal mass
      was en-bloc resected together with the left adrenal gland. Macroscopic sectioning
      showed a smoothly rounded 29 x 21 x 12 cm tumour attached to a normal left
      adrenal gland, weighing 4050 gr. The huge size of the neoplasm, the several areas
      of necrosis, the size and monomorphic appearance of the cells, and the large
      number of mitotic figures afforded a diagnosis of malignant phaeochromocytoma.

PMID- 8867507
TI  - The 1928 eruption of Mount Etna volcano, Sicily, and the destruction of the town
      of Mascali.
AB  - In November 1928 there was an eruption of Mount Etna, Sicily, which led to lava
      largely destroying the town of Mascali, situated low on the eastern flank of the
      volcano. Destruction of the town took just over a day but there was an orderly
      evacuation of its inhabitants and, with help from the military, families were
      able to remove furniture and fittings from their houses. Evacuees were relocated
      to nearby towns staying with relatives, friends or in hired apartments.
      Rebuilding Mascali provided an opportunity for the fascist government of the time
      to demonstrate efficient centralised planning. A completely new town was built on
      a grid-iron plan with many of the buildings reflecting the 'fascist architecture'
      of the time. The town was complete by 1937 and housing condztzons were very
      advanced in comparison with other towns in the region. The 1928 eruption is
      important as it was the most destructive on Etna since 1669 when the city of
      Catania was overwhelmed. In terms of hazard and risk assessment the 1928 eruption
      demonstrates that lava can reach the lower flanks of the volcano within a short
      period after the onset of an eruption.

PMID- 8867506
TI  - Pseudotumour cerebri as a side effect of leuprorelin acetate.
AB  - Leuprorelin acetate is a synthetic nona-peptide analogue of the naturally
      occurring gonadotrophin releasing hormone LH-RH (hypothalamus), used in the
      treatment of sterility, endometriosis or prostatic cancer. In a 35 year old
      woman, treated with leuprorelin acetate, after 5 months treatment, the side
      effects (hot flushes, sweating, sleeping disorders), appeared to be rather
      unbearable. Medication was ended. The endocrine reversion to the normal
      physiological balance was association with high fever (38.9 degrees C) during an
      8 day period. Increasing scotomas resulted in a gradual loss of eyesight in one
      eye, associated with a normal visual acuity. Unilateral papilloedema was
      observed, indicating the possibility of tumor cerebri. Fluorescein angiography
      demonstrated an intense leakage of the right optic disc. No signs of retinal
      vascular malformations were seen. The eye pressure was normal. No signs of
      hemorrhages were observed. Visual field examination showed an enlarged blind spot
      with a few scotomas above the centre of fixation. CT scan of the brain was
      normal, the cerebrospinal fluid (CSF) was normal, indicated by IgG production.
      Six months after ending the leuprorelin acetate treatment, the eyesight was
      spontaneously 100% recovered. It is most likely that leuprorelin acetate is
      responsible for the emergence of pseudotumor cerebri. As described by Prof. Sidi
      et al(1), leuprorelin strongly induces increased liquor pressure, being the
      intermediate mechanism between hormonal treatment and an ante grade mechanical
      force, on the optic nervus. Because of the risk of permanent loss of eyesight, it
      is strongly advised to verify eye parameters conscientiously during leuprorelin
      treatment.

PMID- 8867508
TI  - From relief to development: food for work in Bangladesh.
AB  - The National Food-assisted Works Programme for Water and Land Development in
      Bangladesh which began as a relief operation in 1975, was designed to evolve
      gradually into a development-oriented programme. This complex and largely
      successful transition offers a study in change of relevance to the current debate
      on the relief-development continuum. What emerges from a review of the Bangladesh
      experience is that the transition from relief to development is as complex as it
      is desirable, and that while there is a 'continuum' of sorts if it can be
      reached, getting there has lately become more arduous.

PMID- 8867509
TI  - Neoliberalism and criticisms of earthquake insurance arrangements in New Zealand.
AB  - Global collapse of the Fordist-Keynesian regime of accumulation and an attendant
      philosophical shift in New Zealand politics to neoliberalism have prompted
      criticisms of, and changes to, the Earthquake and War Damage Commission.
      Earthquake insurance arrangements made 50 years ago in an era of collectivist,
      welfarist political action are now set in an environment in which emphasis is
      given to competitive relations and individualism. Six specific criticisms of the
      Commission are identified, each of which is founded in the rhetoric and ideology
      of a neoliberal political project which has underpinned radical social and
      economic changes in New Zealand since the early 1980s. On the basis of those
      criticisms, and in terms of the Earthquake Commission Act 1993, the Commission
      has been restructured. The new Commission is withdrawing from its primary
      position as the nation's non-residential property hazards insurer and is
      restricting its coverage of residential properties.

PMID- 8867510
TI  - Protecting tourists from death and injury in coastal storms.
AB  - Hurricanes, typhoons, tsunamis and other storms force thousands to flee coastal
      regions every year. In many cases, resort areas have been severely damaged and
      tourists placed in jeopardy. This article examines ways tourist businesses can
      and already have protected holiday-makers from coastal storm hazards through
      emergency evacuation and other measures. Using data from a sample of large and
      small hotels in New Orleans, Louisiana, we find considerable variation in
      protective behaviour. To explain this variation, we look at how perceptions and
      preparedness differ by both managerial and organisational characteristics. We
      then suggest a variety of measures that can be taken by hotels in coastal resort
      areas to reduce risk.

PMID- 8867511
TI  - Disaster management and government intervention in PNG: the case of Lae.
AB  - This paper describes government intervention in two flood disasters in Lae before
      and after the establishment of the Papua New Guinea disaster management body. It
      first describes the objectives behind the establishment of this, and second, it
      examines the organisational response to the 1983 and 1992 disasters in Lae.
      Disaster response in terms of relief operations is generally prompt and
      spontaneous but can at best be described as haphazard, unsystematic and often
      uncoordinated. Both national and provincial disaster committees are, in many
      aspects, ill equipped in terms of capabilities, skills and resources. Many
      disaster operations are unable to ensure an immediate return of the victim's
      lives to normality--the ultimate objective of any disaster management.

PMID- 8867512
TI  - Awareness, preparedness and adjustment measures of river-bank erosion-prone
      people: a case study.
AB  - People prone to the effects of river-bank erosion are well aware of the hazard
      they face, but see it as an unavoidable evil. Communities' lack of success in
      combating erosion can be attributed to their poverty and to their not knowing
      about any means to mitigate its effects. Households in safer areas have reduced
      their dependency on agriculture and developed more scope for non-farm activities,
      however, this is often difficult given the limited development of local
      enterprise. The major parameters that influence the adjustment measures after
      erosion are the education, skills, occupation and financial state of those
      affected. Those most vulnerable are households very much dependent on
      agriculture: for them resettlement to distant urban areas is not an option.

PMID- 8867513
TI  - Frederick C. Cuny 1944-1995.

PMID- 8867514
TI  - International conference on natural disasters, IDNDR National Committee/Peruvian
      National Institute of Civil Defence/Peruvian National Geological Institute,
      Huaraz, Peru, 29 May-1 June, 1995.

PMID- 8867515
TI  - The immunopharmacology of the opsoclonus-myoclonus syndrome.
AB  - The opsoclonus-myoclonus syndrome (OMS) is a potentially devastating
      paraneoplastic or paraviral syndrome. Although it is a rare disorder, it has
      major implications for cancer, virology, immunology, developmental neurobiology,
      and molecular pharmacology. The mechanism of brain injury in OMS is unknown, but
      evidence suggests immune system dysregulation. This article surveys recent
      clinical and laboratory evidence for the autoimmune theory and discusses how some
      current therapies for OMS may exert their effects through immunomodulation.
      Specific testable hypotheses on the immunologic defect in OMS involving both B
      cells and T cells, the nature and mechanisms of brain injury, and their clinical
      correlations are proffered. The current therapeutic armamentarium provides a
      broad spectrum of nonselective immunotherapies, including noncytotoxic and
      cytotoxic drugs, intravenous immunoglobulins, and plasma exchange, some selected
      for induction and others for maintenance. The use of combination immunotherapies
      may allow steroid sparing, targeting of more than one immunologic effector
      pathway, and a mixture of early- and late-acting drugs. More selective
      immunotherapies, now available or in preclinical and clinical trials, have great
      potential for the treatment of OMS but require precise information on the
      underlying immunological problem. These data provide possible new directions for
      immunologic research and therapy in OMS.

PMID- 8867516
TI  - Lithium blocks 45Ca2+ uptake into platelets in bipolar affective disorder and
      controls.
AB  - The basal uptake of radiolabelled 45Ca2+ into platelets and the effect of 1 mM
      lithium on uptake was measured in manic (n = 13) and depressed (n = 15) patients
      with bipolar disorder and in controls (n = 13). Lithium was significantly
      associated with inhibition of uptake of 45Ca2+ into platelets in all three
      groups. There were no significant intergroup differences in either basal levels
      of calcium uptake or the effects of lithium on calcium uptake (analysis of
      variance).

PMID- 8867517
TI  - Lack of neurotoxic effect of diethylpropion in crack-cocaine abusers.
AB  - Dopamine agonists have been used with some success in treating cocaine addiction.
      However, both cocaine and psychostimulants have been reported to produce
      neurotoxic effects. We evaluated the effect of the stimulant diethylpropion on
      cognitive performance in a double-blind, placebo-controlled trial. Forty-six
      abstinent crack-cocaine users received either placebo, 25-mg, 50-mg, or 75-mg
      doses of diethylpropion. Patients were tested at baseline and again after 9-14
      days of medication. There were no differences between placebo and medication
      groups on any test, indicating that, within the time frame studied,
      diethylpropion does not produce neurotoxic effects that can be detected with
      standardized neuropsychological tests.

PMID- 8867518
TI  - Apomorphine tolerance in Parkinson's disease: lack of a dose effect.
AB  - The development of tolerance to dopaminergic drugs may be important in the long
      term therapy of Parkinson's disease. In this study, we sought to determine
      whether tolerance developed during infusions of apomorphine and if there was
      evidence of any dose dependency. Eight patients with Parkinson's disease received
      4- to 6-h infusions of apomorphine at low, medium, and high rates on consecutive
      days. Before and after each infusion, test boluses of apomorphine were
      administered to measure sensitivity to the drug. The duration of motor effects
      after the postinfusion boluses were reduced in comparison to those of the
      preinfusion boluses, indicating that tolerance developed during the infusions.
      The infusion rate did not affect the responses to the postinfusion test boluses.
      Our observations indicate that tolerance develops to the antiparkinsonian effect
      of apomorphine after several hours of its constant infusion, but is not
      influenced by the dose of drug administered.

PMID- 8867519
TI  - Effect of subcutaneous administration of levodopa ethyl ester, a soluble prodrug
      of levodopa, on dopamine metabolism in rodent striatum: implication for treatment
      of Parkinson's disease.
AB  - Levodopa ethyl ester (LDEE), a highly soluble prodrug of levodopa, was
      synthesized and administered to mice and rats subcutaneously or
      intraperitoneally. Striatal levels of levodopa, dopamine, and the dopamine
      metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined using high
      performance liquid chromatography with electrochemical detection and compared
      with those obtained after intraperitoneal injections of levodopa. LDEE injections
      produced significant and rapid elevations of striatal levodopa, dopamine, and
      DOPAC, which were similar to those achieved after levodopa administration, with
      similar dose-response curves. The elevations achieved by LDEE given s.c. were
      higher than those achieved after i.p. administration and lasted for longer
      periods. In addition, intraperitoneal administration of levodopa or LDEE to rats
      with unilateral 6-hydroxydopamine (6-OHDA) nigral lesions produced similar
      contraversive circling responses. We suggest that LDEE may be a beneficial
      antiparkinsonian agent. It has potential pharmacokinetic advantages that are
      superior to those of levodopa itself, and its subcutaneous administration may
      become an effective rescue strategy to overcome "off" situations in patients with
      Parkinson's disease and response fluctuations.

PMID- 8867520
TI  - Effects of terguride on anterior pituitary function in parkinsonian patients
      treated with L-dopa: a double-blind study versus placebo.
AB  - In a randomized double-blind study, 20 parkinsonian patients (suffering from the
      disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for
      0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth
      hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin
      like growth factor (IGF-I) secretions were studied before and after the morning
      dose of levodopa (250 mg p.o.), both before and at the end of study period. At
      the beginning of the study, basal hormonal levels were within normal limits, and
      levodopa administration induced a significant suppression in PRL and TSH levels
      (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results
      were observed at the end of the study period in the placebo group. Addition of
      terguride induced a significant suppression in basal PRL levels (p < 0.01),
      whereas levodopa-induced hormonal changes were unaffected. These data suggest
      that the hypothalamic dopaminergic function that controls anterior pituitary
      hormones is preserved in parkinsonian patients, regardless of both the duration
      of the disease and the long-term treatment with levodopa. The strong additional
      prolactin-lowering effect of terguride indicates long-lasting dopaminergic
      effects, as is already known from hyperprolactinemic conditions. The dopaminergic
      effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride
      treatment. The anti-dopaminergic effects of terguride observed in the motor
      system in animal studies, as well as in levodopa-induced dyskinesias in
      parkinsonian patients, could not be observed in the case of the dopaminergic
      control of anterior pituitary hormones under the conditions of this study.

PMID- 8867521
TI  - Electroencephalographic findings with low-dose clozapine treatment in psychotic
      Parkinsonian patients.
AB  - Twenty patients with Parkinson's disease (PD), who developed delusions and
      psychotic behavior, underwent electroencephalogram (EEG) recordings before and
      during treatment with low-dose clozapine. Resolution of the psychotic features
      was observed in all cases. The EEG was unaltered in 15, whereas five patients
      exhibited increased generalized or focal slowing when compared with the
      pretreatment tracings. These findings contrast with the high incidence of EEG
      abnormalities, including epileptiform activity, which are observed when larger
      doses of clozapine are used in schizophrenic patients, but they underscore that
      even in low doses, clozapine may cause EEG changes.

PMID- 8867522
TI  - Functional preservation of benzodiazepine receptors of the primary somatosensory
      cortex in Creutzfeldt-Jakob disease: a pharmacologic-evoked potential study.
AB  - In previous studies, we demonstrated that the benzodiazepine (BZP) receptors of
      the visual system are functionally preserved in Creutzfeldt-Jakob disease (CJD).
      We hypothesized that such a functional preservation is not confined to the visual
      system. In a 74-year-old woman suffering from CJD, three consecutive recording
      sessions of somatosensory cortical evoked potentials (SEPs) by right median nerve
      stimulation were carried out: (a) basal condition, without any pharmacologic
      treatment; (b) 1 min after i.v. administration of 10 mg diazepam (DZP); (c) 2.5
      min after i.v. administration of 3 mg FMZ, a high-affinity receptor
      benzodiazepine antagonist. DZP greatly decreased the amplitude of SEP early
      components, whereas flumazenil (FMZ) reversed such an effect. The results of this
      study, paralleling our previous findings on the visual system in CJD,
      demonstrated functional preservation of BZP receptors in the somatosensory
      pathways as well.

PMID- 8867524
TI  - Response to Garrido et al.: "Side effects of the catechol-O-methyl-transferase
      inhibitor Ro 40-7592 in rabbits".

PMID- 8867523
TI  - Analgesic efficacy of the kappa-receptor agonist, enadoline, in dental surgery
      pain.
AB  - To study the analgesic efficacy of enadoline, a selective agonist of the kappa
      opioid receptor, a double-blind, randomized comparison was made of enadoline
      versus placebo and a combination of acetaminophen-codeine in patients with pain
      after surgical extraction of impacted molar teeth. An initial study involving a
      comparison of enadoline, a combination, and placebo failed to show any analgesic
      effect of enadoline. Therefore, a second study with the same design but using
      higher doses of enadoline was conducted. Despite continued safety and
      tolerability even at the higher doses, enadoline could not be shown to be
      superior to placebo. The acetaminophen-codeine combination was significantly more
      effective than enadoline or placebo. Enadoline did not show analgesic efficacy in
      this study. Possible reasons for this lack of efficacy are discussed.

PMID- 8867525
TI  - The Gompertz equation as a predictive tool in demography.
AB  - The Gompertz demographic model describes rates of aging and age-independent
      mortality with the parameters alpha and A, respectively. Estimates of these
      parameters have traditionally been based on the assumption that mortality rates
      are constant over short to moderate time periods. This assumption is questionable
      even for very large samples assayed over short time intervals. In this article,
      we compare several methods for estimating the Gompertz parameters, including some
      that do not assume constant mortality rates. A maximum likelihood method that
      does not assume constant mortality rates is shown to be best, based on the bias
      and variance of the Gompertz parameter estimates. Moreover, we show how the
      Gompertz equation can then be used to predict mean longevity and the time of the
      nth percentile of mortality. Methods are also developed that assign confidence
      intervals to such estimates. In some cases, these statistics may be estimated
      accurately from only the early deaths of a large cohort, thus providing an
      opportunity to estimate longevity on long-lived organisms quickly.

PMID- 8867527
TI  - Early appearance of age-associated deterioration in mitochondrial function of
      diaphragm and heart in rats treated with doxorubicin.
AB  - Age-associated deterioration of mitochondrial energy transduction seems to be a
      major contributory factor to age-related decline in organ function. Free radicals
      are likely to be involved in the age-related decline in mitochondrial function.
      This study was designed to elucidate whether or not doxorubicin, a radical
      generating drug that was administered to 7-week-old rats, affects age-associated
      mitochondrial functional changes in diaphragm, heart, and liver. Mitochondria
      from each tissue were prepared from rats aged 7, 13, 20, 28, 35, and 55 weeks,
      and the activities of four complexes in the mitochondrial energy transduction
      system were measured enzymatically. In diaphragm mitochondria of the control
      group, the complex I activity in 28-week-old rats declined to 82% of the activity
      in rats aged 7 weeks, and the complex IV activity in 55-week-old rats declined to
      70% of the activity in rats aged 7 weeks. On the contrary, a significant decrease
      in the activity of complex I in rats aged 20 weeks (84%) and that of complex IV
      in rats aged 35 weeks (86%) were observed in the doxorubicin-treated group. In
      heart mitochondria, age-related changes in activities of complexes I and IV did
      not appear in rats aged up to 55 weeks, whereas significant decreases in the
      activities of complexes I (78%) and IV (90%) were observed in rats aged 35 weeks
      in the doxorubicin group. Age-related changes in liver mitochondria were not
      found in rats aged up to 55 weeks, and no deleterious effects of doxorubicin were
      observed in liver mitochondrial function. From these results, the early
      appearance of aging effects on mitochondrial function was observed in rats
      treated with doxorubicin particularly in postmitotic cells.

PMID- 8867526
TI  - The role of obesity and cardiovascular fitness in the impaired glucose tolerance
      of aging.
AB  - The prevalence of impaired glucose tolerance (IGT) increases with aging. Although
      some data suggest that age is independently associated with IGT, other studies
      suggest that age-associated changes in body composition and reduced
      cardiovascular fitness are responsible for the development of IGT. We, therefore,
      examined the relationship of age, total and regional adiposity, and level of
      fitness (VO2max) to the presence of IGT in 155 healthy, nondiabetic, nonsmoking,
      older community dwelling men. Sixty-two of 155 men (40%) had IGT, while 93 men
      (60%) had normal glucose tolerance (WHO criteria). The subjects with IGT were of
      similar age (61.0 +/- 1.0 vs. 59.0 +/- 0.7 years, p = 0.49) and had the same
      maximal aerobic capacity, (VO2max) (42.0 +/- 1.0 vs. 44.0 +/- 0.8 mL/kg ffm/min,
      p = 0.42), but had a higher waist to hip ratio (WHR) (0.98 +/- 0.01 vs. 0.96 +/-
      0.01, p = 0.005) and percent body fat (30.0 +/- 0.4 vs. 26.0 +/- 0.6, p = 0.004)
      than the men with normal glucose tolerance. In univariate analysis, the 2-h
      glucose level correlated positively with percent body fat (r = 0.30, p = 0.0002),
      WHR (0.24, p = 0.002), and age (r = 0.17, p = 0.03) and negatively with VO2max (r
      = -0.23, p = 0.005). In both multiple logistic and linear regression analyses,
      percent body fat was the only independent predictor of IGT (p = 0.002). These
      results suggest that the age-associated increase in total adiposity is a major
      contributor to the development of IGT in middle-aged and older men. Thus,
      lifestyle modifications that reduce body fat should reduce the risk for IGT and
      the development of noninsulin-dependent diabetes mellitus in the elderly.

PMID- 8867529
TI  - Mortality dynamics of density in the Mediterranean fruit fly.
AB  - The effects on medfly age-specific mortality of three types of densities-
      initial, current, and cumulative--were examined using sex-specific data from two
      sets of studies: (1) previous research on mortality patterns in 1.2 million
      individuals maintained in 167 different cages (1992 Science 258, 457) and ii)
      density experiments using a total of 210,000 individuals contained in 49 cages
      and maintained at one of three initial densities--2500, 5000 and 10,000
      flies/cage. A central death rate was computed for each of the 216 cages at
      specified numerical levels (e.g., 5000, 4000, 1000, 500, 100, and so forth),
      which was distributed over a range of ages. This yielded a series of mortality
      schedules at "equivalent current densities." Two main results are reported.
      First, the leveling off and decline in mortality at the most advanced ages as
      observed in the original study of 1.2 million medflies cannot be explained as an
      artifact of declining current densities at older ages. Second, increased initial
      density heightened the mortality level at each age but had essentially no effect
      on mortality pattern. The overall methodology and many of the results are
      believed to be general and thus both logistical and conceptual implications for
      gerontology and population biology are discussed.

PMID- 8867528
TI  - Age-related postreceptor mechanisms: changes in adenylate cyclase but not
      phosphodiesterase in isolated mouse renal medullary collecting ducts.
AB  - Urine concentrating ability declines with increasing age, partly due to an
      impaired response of kidney medullary collecting ducts to the antidiuretic
      hormone, vasopressin. We investigated this change in isolated mouse medullary
      collecting ducts by measuring the activity of adenylate cyclase and
      phosphodiesterase, which catalyse the formation and hydrolysis of cAMP,
      respectively. Adenylate cyclase activity was measured in the presence of
      vasopressin (which stimulates adenylate cyclase via the receptor) or forskolin
      (which directly stimulates the catalytic subunit). We showed an age-related
      decrease in the catalytic subunit of adenylate cyclase, and no difference in the
      activity of phosphodiesterase, indicating that a reduction in the catalytic
      subunit of adenylate cyclase contributes towards the age-related decrease in
      cyclic AMP response of kidney to vasopressin.

PMID- 8867530
TI  - Age and gender effects on 1,25-dihydroxyvitamin D3-regulated gene expression.
AB  - Several factors involved in regulation of bone mineral metabolism were compared
      in male and female Fischer 344 rats of different ages (1, 2.5, 6, and 18 months).
      Plasma 1,25-(OH)2D3 concentrations decreased with age in rats of both genders.
      Abundance of calbindin-D28K and its mRNA in kidney and calbindin-D9K and its mRNA
      in duodenum also decreased with age in both male and female rats. Renal 24
      hydroxylase activity and 24-hydroxylase mRNA content were elevated significantly
      in 18-month-old males and females, compared with younger ages. These data suggest
      that increased renal catabolism of 1,25-(OH)2D3 may be responsible for low plasma
      1,25-(OH)2D3 concentrations observed in older animals. Plasma PTH and 1,25
      (OH)2D3 concentrations, renal 24-hydroxylase enzyme activity and 24-hydroxylase
      mRNA content, duodenal 24-hydroxylase mRNA abundance, and duodenal calbindin-D9K
      and calbindin-D9K mRNA content were greater in males than in females at 2.5
      months of age. Lower plasma 1,25-(OH)2D3 concentrations in females seem to
      explain observed gender differences in expression of 1,25-(OH)2D3-stimulated
      genes. The combined effects of these gender differences at ages when peak bone
      density is being developed may contribute to the greater incidence of
      osteoporosis in females than in males.

PMID- 8867531
TI  - Effect of aging on lipid peroxide levels induced by L-glutamic acid and estimated
      by means of a thiobarbituric acid test in rat brain tissue.
AB  - Studies of age-related changes based on the thiobarbituric acid (TBA) test appear
      to be inconsistent and contradictory. In our work, real basal (hypothetical,
      corrected to the zero concentration of atmospheric oxygen), basal (atmospheric
      oxygen-stimulated) and stimulated (L-glutamic and hydrochloric acids) levels of
      TBA-reactive products (TBARP) were estimated in the brain (hippocampus--HPC,
      cortex--COR, cerebellum--CRB) from young (3 months) and old (28 months) male and
      female Wistar rats. The values of basal levels of TBARP were different in young
      (HPC > COR > CRB) as well as in old animals (COR > CRB > HPC). Thus, the process
      of aging caused a significant decrease in the HPC (to 72%) and no change in the
      COR and CRB. Levels stimulated by L-glutamic acid were significantly decreased
      (COR, CRB) and unchanged (HPC) in old compared to young animals. The real basal
      levels estimated by regression analysis seem to be higher in the brain tissue
      damaged by aging. We discuss the usefulness of the TBA test applied to aged
      tissue, the effect of acidosis, the effectivity of L-glutamic acid to generate
      free radicals and the differences between individual brain areas.

PMID- 8867532
TI  - New developments in the pathogenesis of systemic vasculitis.
AB  - Over the past few years, novel pathogenic mechanisms leading to vascular
      inflammation and injury have been discovered. Circumstantial evidence that
      supports a pathogenic role for antineutrophil cytoplasmic antibodies (ANCA) in
      mediating vessel damage includes in vitro studies showing that ANCA promote
      neutrophil activation and endothelial injury. In addition, several animal models
      of ANCA-induced vasculitis and glomerulonephritis have been developed. The role
      of T cell-mediated immune mechanisms in vasculitis has been strengthened by
      molecular studies demonstrating clonal expansion of selected T cell populations
      in inflammatory foci, possibly recognizing a disease-relevant antigen. There is
      also increasing awareness of the important role that adhesion molecules may play
      in the development of vascular inflammatory infiltrates. The putative
      participation of cytokines and growth factors, released by inflammatory cells, in
      vessel occlusion and organ dysfunction, is a focus of increasing research
      activity.

PMID- 8867533
TI  - Clinical disease activity in systemic vasculitis.
AB  - Long-term follow-up data indicate that the systemic vasculitides are chronic
      relapsing diseases with high morbidity. It is therefore of paramount importance
      to distinguish activity, which requires cytotoxic or immunosuppressive therapy,
      from damage requiring rehabilitation. Damage due to underlying disease or
      treatment highlights the need for more effective, less toxic treatment regimens.
      An integrated package for clinically based assessment of disease activity in
      systemic vasculitis, the Vasculitis Integrated Assessment Log, has been accepted
      for further evaluation and implementation by the European Community Study Group
      for use in therapeutic trials. The added value of serologic tests and
      inflammatory markers in clinical assessment is becoming more clear, and
      unsuspected disease activity has been revealed by biopsy and imaging of standard
      sites or affected areas. Integration of these data should enable characterization
      of high- and low-risk patient subgroups to determine specific therapies.

PMID- 8867534
TI  - New insights into the epidemiology of systemic vasculitis.
AB  - Because of the relative rarity of the conditions, epidemiologic investigation of
      systemic vasculitis is a challenging prospect. Previous work in this area has
      been primarily in the form of descriptive studies and therapeutic trials, which
      have increased awareness of these syndromes among clinicians. However, compared
      with other diseases, little is known about the epidemiology of the systemic
      vasculitides. Although significant progress has been made during the past year to
      estimate incidence and prevalence rates of disease, particularly for giant cell
      arteritis and Kawasaki disease, further studies are needed to determine risk
      factors for initial expression and relapses of vasculitis, biologic markers of
      disease progression, comorbidities, long-term outcomes, and cost of care and
      disability.

PMID- 8867535
TI  - Vasculitis associated with infectious agents.
AB  - The HIV infection epidemic and, with it, the resurgence and emergence of old and
      new opportunistic microbes, have sparked off a renewed interest in vasculitis
      associated with infectious agents. Current investigations focus on identification
      of "newer" infectious agents, unusual clinical manifestations, and methodologic
      refinement in diagnosis and treatment. This article briefly reviews the
      background of infection-associated vasculitis and highlights some of the newer
      and unusual aspects of vasculitis known to be associated with nonviral and viral
      infections.

PMID- 8867536
TI  - Vasculitides associated with malignancy.
AB  - Vasculitides associated with malignancies are infrequent. We can group this
      syndrome under three broad clinical categories: vasculitide-associated
      malignancies or true paraneoplastic syndrome, malignancies masquerading as
      vasculitides, and vasculitides masquerading as malignancies. Recent new
      etiopathogenic hypotheses are discussed: an immunologic dysregulation with either
      handling, production, or elimination of circulating immune complexes; an
      immunogenetic abnormality with autogenes and oncogenes with up- and/or
      downregulation of cell proliferation through abnormal apoptosis; and direct
      involvement of a virus such as human T cell lymphotropic virus type I or Epstein
      Barr virus. An update on several recently reported associations between
      vasculitides and malignancies is presented.

PMID- 8867537
TI  - Drug-induced vasculitis.
AB  - Vasculitis resulting from drug use includes a wide variety of clinical and
      pathologic conditions that are, in general, empirically defined and poorly
      understood. Further complicating our grasp of these disorders are ambiguous terms
      such as hypersensitivity vasculitis, allergic vasculitis, leukocytoclastic
      vasculitis, serum sickness, and others, which are often used interchangeably
      without clear definition. The clinical picture varies widely from self-limiting
      to progressive and even fatal illness. These syndromes have now been reported in
      association with newer classes of therapeutic agents including biologic response
      modifiers. Vasculitis affecting the central nervous system may be related to a
      variety of drugs and remains one of the more important syndrome sets within the
      spectrum of drug-induced vasculitis. These disorders are clinically important,
      because removal of the offending drug often is associated with regression of the
      vasculitic condition.

PMID- 8867538
TI  - Kawasaki disease.
AB  - The 5th International Kawasaki Disease Symposium was held in May 1995 in Fukuoka,
      Japan. No one infectious agent has been found to initiate the syndrome, although
      the occurrence of Kawasaki disease in epidemics and its resemblance to toxic
      shock syndrome make an infectious etiology seem most likely.

PMID- 8867539
TI  - Rheumatic manifestations of malignancy.
AB  - Rheumatic manifestations of malignancy include a wide spectrum of osteoarticular,
      muscular, glandular, endocrinologic, and systemic features, posing a therapeutic
      challenge. The clinician should be aware that Sjogren's syndrome,
      polymyositisdermatomyositis, rheumatoid and rheumatoid-like arthritis,
      polymyalgia rheumatica and temporal arteritis, and diverse osteomuscular
      conditions may be the immunopathogenic features of a neoplasm, the direct
      consequence of osteomuscular tumors, the effect of tumor-associated hormones, or
      the consequence of cancer therapy. The principal articles that have appeared in
      the past year on these associations are discussed. We also review the association
      of x-ray irradiation and cancer in patients with ankylosing spondylitis.

PMID- 8867540
TI  - Immunodeficient states and associated rheumatic manifestations.
AB  - The molecular mechanisms of the primary immunodeficiencies have been further
      explored and provide insights into the regulation of the immune response and its
      role in autoimmune disease, infection, and malignancy. The critical role of CD40
      CD40 ligand-mediated effects in T cell-dependent B cell activation, shown through
      the study of patients with common variable immunodeficiency and hyper IgM
      syndrome, suggests a potential narrow target for immunomodulatory therapy. A
      mouse model for chronic granulomatous disease has been developed and promises to
      be a source of future information. Optimal cost-effective therapy for primary
      immunodeficiencies continues to be defined, with the results of a large series of
      patients treated with subcutaneous immunoglobulin infusions reported. Further
      experience with polyethylene glycol adenosine deaminase and interleukin-2
      conjugates is discussed.

PMID- 8867541
TI  - Rheumatologic features of hematologic disorders.
AB  - The rheumatologic manifestations of hemophilia and the hemoglobinopathies have
      been previously reviewed. Recent observations on the management and complications
      of these disorders are presented. Although rheumatologic manifestations are well
      recognized in leukemias and lymphomas, most of the observations have been based
      on small series of patients and case reports. This review focuses on leukemias
      and lymphomas, and brief reference is made to the myelodysplastic syndromes.

PMID- 8867542
TI  - Amyloidosis.
AB  - Developments concerning amyloidosis associated with rheumatic diseases or often
      causing musculoskeletal symptoms are reviewed. The pathogenesis, clinical
      manifestations, diagnosis, and therapy of amyloid A, amyloid light-chain, and
      amyloid beta 2-microglobulin amyloidosis are discussed from the standpoint of a
      clinical rheumatologist. The biology of the precursor protein serum amyloid A
      (SAA) has been extensively studied, and a new assay for SAA has been developed.
      In amyloid beta 2-microglobulin amyloidosis, modified beta 2-microglobulin may
      function as a pathogenic factor that initiates an inflammatory reaction in which
      macrophages produce cytokines that induce osteoclastogenesis and bone resorption.
      Further experience with serum amyloid P component scintigraphy in the diagnosis
      and monitoring of amyloidosis has accumulated. Guidelines for the dosage of
      colchicine in the treatment of amyloidosis associated with familial Mediterranean
      fever have been published. In amyloid light-chain amyloidosis, intensive
      chemotherapy in combination with bone marrow transplantation or autologous stem
      cell infusion has potential therapeutic significance.

PMID- 8867543
TI  - Rheumatologic manifestations of renal disease.
AB  - The rheumatologic manifestations of renal disease are commonly encountered and
      include crystal deposition disease and renal osteodystrophy. In addition, renal
      transplantation carries important rheumatologic manifestations. Basic calcium
      phosphate crystal deposition remains an important source of morbidity in renal
      disease, but it can be largely prevented. Early preventive measures and use of
      biochemical markers for assessment allow effective management of renal
      osteodystrophy. Effective treatment is available for the acute bone pain syndrome
      seen after transplantation, and the natural history of osteonecrosis in such
      patients may be more benign than previously considered, thus affecting current
      management schemes for this complication.

PMID- 8867544
TI  - Endocrine disorders and musculoskeletal diseases.
AB  - Some clinical features observed in diabetes mellitus suggest secondary Sjogren's
      syndrome, and the effect of autonomic neuropathy on tear production is analyzed.
      Limited joint mobility in diabetes mellitus continues to attract attention, and a
      number of suggestions for further studies are discussed. Neurophysiologic
      assessment of the median nerve distinguishes diabetic polyneuropathy from carpal
      tunnel syndrome; however, Martin-Gruber anastomosis may modify nerve conduction
      measurements. Fracture rate does not appear to be increased in diabetes mellitus.
      The role of confounding variables and a dose-dependent effect of thyroxine
      therapy on bone mass is discussed. The possible association of hypothyroidism
      with gout is debated. Autoimmune thyroid diseases may be added to the list of
      conditions that produce anticardiolipin antibodies without the clinical
      manifestations of antiphospholipid syndrome.

PMID- 8867545
TI  - Rheumatic manifestations of tropical diseases.
AB  - It is becoming increasingly recognized that a variety of tropical infectious
      diseases may be associated with a wide range of rheumatic infections. These
      include viral arthropathies such as O'nyong-nyong, chikungunya, and dengue.
      Parasitic infections such as filariasis, schistosomiasis, and amoebiasis can be
      associated with various joint problems. Diseases such as tuberculosis, rheumatic
      fever, leprosy, and brucellosis, although more common in the tropics, continue to
      present with rheumatic features in Western countries. Thus, with increasing world
      travel and migration, there is a need for increasing awareness and further study
      of tropical diseases and their rheumatic manifestations.

PMID- 8867546
TI  - Vasculitic syndromes.

PMID- 8867547
TI  - Systemic disorders with rheumatic manifestations.

PMID- 8867548
TI  - Postoperative joint infections in rheumatoid arthritis patients on methotrexate
      therapy.
AB  - The effect of low dose methotrexate (MTX) on postoperative complications in
      rheumatoid arthritis patients undergoing elective total joint arthroplasty was
      observed prospectively in 32 patients. Patients were assigned to discontinue MTX
      the week prior to and during the week of surgery (Group 1, n = 19) or to continue
      MTX throughout the perioperative period (Group 2, n = 13). Nineteen patients in
      Group 1 had 26 procedures, with no postoperative infections. Thirteen patients in
      Group 2 had 16 procedures, with 4 postoperative infections: 2 infected
      prostheses, 1 infected joint fusion, and 1 deep wound infection (P = .03). No
      patient had a postoperative flare of rheumatoid arthritis. Temporary
      discontinuation of MTX prior to joint arthroplasty appears to decrease the risk
      of postoperative infection.

PMID- 8867549
TI  - Orthopedic surgery residents and the CDC and AAOS HIV precautionary measures.
AB  - A randomized national survey of orthopedic surgery residents concerning their
      knowledge, attitudes, and behaviors of the Centers for Disease Control's and the
      American Academy of Orthopaedic Surgeons' (AAOS) universal human immunodeficiency
      virus (HIV) precautionary measures was conducted. The residents' basic knowledge
      about the HIV precautionary measures was, in general, poor. Thirty-seven percent
      indicated that they were "uncertain" or "would not" care for HIV positive
      patients. Further, the residents' practice behaviors in many instances did not
      fulfill prescribed universal precautions. Sound educational and professional
      programs, such as those initiated by the AAOS, are needed to increase the
      knowledge and improve the practice behaviors of orthopedic residents.

PMID- 8867550
TI  - Magnetic resonance imaging in the evaluation of heel pain.
AB  - This study demonstrates magnetic resonance findings in 16 patients (25 heels)
      with heel pain. Sixteen of 25 (64%) studies demonstrated abnormalities which
      could be related to the etiology of their heel pain. Eleven of 16 abnormal scans
      demonstrated thickening of the plantar aponeurosis with associated fibrosis (7 of
      11), and a tear of the flexor digitorum brevis (1 of 11). One study demonstrated
      changes in the heel pad consistent with fluid. The other four abnormal studies
      demonstrated changes thought to be consistent with bilateral fibrous
      calcaneonavicular coalitions, subtalar arthrosis and tenosynovitis of the
      posterior tibial, flexor digitorum longus, and flexor hallucis longus tendons.

PMID- 8867551
TI  - Ischemic contracture of the foot and ankle: principles of management and
      prevention.
AB  - A variety of clinical presentations can be encountered following compartment
      syndrome of the leg and foot. Deformity and functional impairment in the foot and
      ankle secondary to ischemia are determined by: 1) which leg compartments have
      been affected and to what degree extrinsic flexor or extensor "overpull" is
      exhibited, 2) degree of nerve injury sustained causing weakness or paralysis of
      extrinsic or intrinsic foot and ankle muscles, 3) which foot compartments have
      been affected and to what degree intrinsic "overpull" is exhibited, and 4) degree
      of sensory nerve injury leading to anesthesia, hypoesthesia, or hyperesthesia of
      the foot. Nonoperative therapy attempts to obtain or preserve joint mobility,
      increase strength, and provide corrective bracing and accommodative foot wear.
      Operative management is undertaken for treatment of residual nerve compression or
      refractory problematic deformities. Established surgical protocols are performed
      in a stepwise fashion, and include: 1) release of residual or secondary nerve
      compression; 2) release of fixed contractures, using infarct excision,
      myotendinous lengthening, muscle recession, or tenotomy; 3) tendon transfers or
      arthrodesis to increase function; and 4) osteotomy or amputation for severe, non
      salvageable deformities.

PMID- 8867552
TI  - Candida albicans infection of prosthetic joints.

PMID- 8867553
TI  - Charcot spinal arthropathy in congenital insensitivity to pain.

PMID- 8867554
TI  - Extraskeletal chondroma of the foot.

PMID- 8867555
TI  - Fibrous hamartoma of infancy.

PMID- 8867556
TI  - Longitudinal tibial stress fracture.
AB  - Fatigue-type stress fractures occur following repetitive loading of normal bone.
      These occur frequently in the tibia, although vertical orientation to the
      fracture is much less common than transverse orientation. Without a convincing
      history of new or accelerated muscular activity, imaging can be difficult to
      interpret and evaluation may require more than one imaging modality to exclude
      other diagnostic considerations, including neoplasm and osteomyelitis.

PMID- 8867557
TI  - Systolic hypertension in critical aortic stenosis and the effect of valve
      replacement.
AB  - All cases of aortic valve replacement (AVR) for critical aortic stenosis (AS) in
      a 3 year period were reviewed and 43 cases were included in the study. Twenty
      patients had systolic hypertension preoperatively by sphygmomanometry and/or by
      measurement of central aortic pressure during cardiac catheterization. These
      patients also had a significantly higher mean left ventricular (LV) peak pressure
      than their normotensive counterparts. Following AVR all 43 patients were
      normotensive. This study suggests that not only can an elevated blood pressure
      (BP) be found in the presence of AS, but that AS itself can cause hypertension,
      in which case AVR can result in normalization of BP. We suggest that the systolic
      hypertension is due to a partial transmission of the higher LV peak pressure
      across the aortic valve, despite the stenotic valve acting as a pressure barrier.
      This effect may be more pronounced the tighter the stenosis.

PMID- 8867558
TI  - Leukocyte responsiveness to substances that activate the respiratory burst is not
      altered in borderline and essential hypertension.
AB  - Activated leukocytes have been implicated in the pathogenesis of hypertension and
      its complications. The present study investigated the activity stage of
      leukocytes for production of reactive oxygen species (ROS) in 17 normotensive
      controls and subjects with borderline (n = 17) or essential hypertension (n = 17)
      using different biological materials (whole blood and isolated polymorphonuclear
      leukocytes (PMNLs)), stimuli (zymosan and formyl-methionyl-leucyl-phenylalanine
      (FMLP)) and ROS detection assays (chemiluminescence, hydrogen peroxide and
      superoxide anion determination). Neither the capacity for extracellular
      generation of oxygen metabolites nor the production of ROS with an intracellular
      origin were significantly different in isolated PMNLs between controls and
      hypertensive subjects. There were no significant differences in the luminol
      amplified zymosan- or FMLP-stimulated whole blood chemiluminescence response. In
      addition, the leukocyte count did not differ between the groups. The results
      suggest that circulating leukocytes of controls and hypertensives existed in a
      resting state in our experimental conditions. We did not find any evidence of
      enhanced basal leukocyte free radical activity in patients with mild or severe
      hypertension.

PMID- 8867559
TI  - Arterial stiffness, hydrochlorothiazide and converting enzyme inhibition in
      essential hypertension.
AB  - In a randomized double blind study, the arterial changes produced either by
      hydrochlorothiazide plus amiloride (Group I), or by hydrochlorothiazide plus
      captopril (Group II) were investigated in two territories of the arterial tree,
      the common carotid artery and the terminal aorta. Arterial echo-tracking
      techniques of high resolution and applanation tonometry were used to evaluate non
      invasively the indices of arterial stiffness and carotid wave reflections. In
      Group I and II, there was a similar significant decrease in brachial blood
      pressure (BP) and carotid diastolic diameter and an increase in aortic compliance
      and distensibility. Groups I and II differed significantly in aortic diastolic
      diameter which decreased in Group I but not in Group II, and in carotid wave
      reflections which were modified in Group II but not in Group I. Thus, captopril
      associated with hydrochlorothiazide resulted in a shift in the carotid arterial
      reflection wave from systole to diastole with no reduction in the aortic
      diastolic dimension. For similar BP reduction, the combination of
      hydrochlorothiazide and amiloride had no significant effect on the carotid
      reflection wave, but caused a significant reduction in the aortic diastolic
      diameter. These intergroup differences were related to the presence or absence of
      converting enzyme inhibition.

PMID- 8867560
TI  - Prevalence of renal artery stenosis in patients with peripheral vascular disease
      and hypertension.
AB  - The aim of this study was to evaluate the prevalence of renal artery stenosis in
      patients with clinical signs of peripheral vascular disease and hypertension. One
      hundred patients, mean age 69 years (range 45-88) with symptoms and clinical
      signs of severe peripheral ischemia, underwent aortography to determine the
      degree of peripheral vascular disease and possible renal artery stenosis. History
      of claudication, and measurement of systolic distal blood pressure (BP) and
      calculation of the Ankle Brachial Index was used to define the severity of
      peripheral vascular disease. A total of 31% had renal artery stenosis (14%
      greater than 50% reduction in luminal diameter). In a subgroup of patients with
      hypertension and peripheral vascular disease (n = 74), 34% had renal artery
      stenosis. In the subgroup of patients with renal artery stenosis, 81% have
      hypertension. Patients with renal artery stenosis and lumen reduction of more
      than 50%, 93% have hypertension (P < or = 0.001). In conclusion this study shows
      that the combination of peripheral vascular disease and hypertension is an
      important clinical clue for renovascular disease. Examination for reno-vascular
      disease in this population should be considered, since the prevalence of the
      condition is high. Furthermore examination for renal vascular disease in this
      population is mandatory, before treatment with angiotensin converting enzyme
      (ACE) inhibitors is initiated, since treatment might lead to serious renal
      function impairment.

PMID- 8867561
TI  - Determinants of the white-coat effect in hypertensive subjects.
AB  - To determine the magnitude and the relationships of the difference between office
      and awake ambulatory blood pressures (BP) (white-coat effect) in ambulatory
      hypertensive patients, 64 consecutive patients referred to the ambulatory BP
      monitoring laboratory were studied. All subjects were evaluated prospectively by
      study nurse, study doctor, and ambulatory BP measurements. Order of measurements
      was randomized and observers were blinded to each others readings. No differences
      were found in the white-coat effects among study nurse (22/14 +/- 20/9 mm Hg),
      study doctor (27/12 +/- 20/10 mm Hg) and referring doctor (19/11 +/- 18/10 mm
      Hg). Similarly, female and male patients exhibited similar white-coat effects on
      the day of ambulatory monitoring. Older patients (> or = 65 years) displayed
      higher mean systolic white-coat effects than younger patients (29 +/- 18 mm Hg vs
      19 +/- 19 mm Hg, P = 0.04). Multivariate analysis using the mean average systolic
      white-coat effect as the dependent variable and age, gender, treatment status,
      body mass index (BMI) and duration of hypertension as independent variables
      showed a significant independent role for age. In contrast, no clinical
      correlates of the diastolic white-coat effect were found. Older patients are more
      likely to display a systolic white-coat effect in the medical care environment.

PMID- 8867562
TI  - Hypertensive retinopathy: a review of existing classification systems and a
      suggestion for a simplified grading system.
AB  - With the advent of sophisticated ophthalmological investigations and a better
      understanding of the pathophysiology and clinical or prognostic correlates of the
      fundal lesions in hypertension, the limitations of early classification schemes
      using simple ophthalmoscopic appearances are increasingly apparent. This review
      describes the existing classification systems for hypertensive retinopathy and
      their limitations, as well as the pathophysiological effects of hypertension on
      the retinal vasculature. A new and simpler grading system for hypertensive
      retinopathy is proposed, dividing the features according to prognosis into two
      categories of non-malignant vs malignant hypertension. Such a simpler, updated
      system for our medical practice has been long overdue.

PMID- 8867563
TI  - Effect of strenuous exercise on agonist-induced platelet cytosolic calcium in
      man.
AB  - Hypertension, which is attenuated by regular aerobic exercise, is associated with
      an increase in cytosolic platelet calcium [Ca+2]i. How aerobic exercise might
      lower blood pressure is unknown. We tested the hypothesis that exercise would
      influence the agonist-induced effect on platelet cytosolic calcium [Ca+2]i.
      Twenty, healthy normotensive men between 20 and 60 years of age (five per decade)
      were studied while resting supine for 30 min and after bicycle ergometry at a
      work load sufficient to achieve a heart rate of 200 beats per min minus age in
      years. On the next day, the protocol was repeated with the subjects exercising at
      75% their maximum heart rate for 6 min. Venous blood was obtained from an
      indwelling cannula. Exercise had no effect on total or ionised serum calcium
      values. Adrenaline values increased from 0.2 +/- 0.03 to 0.55 +/- 0.1 (s.e.m.)
      nmol/l (P < 0.05), while noradrenaline increased from 1.46 +/- 0.18 to 4.72 +/-
      0.44 nmol/l (P < 0.05). Resting platelet [Ca+2]i concentrations were 95.4 +/- 3.9
      and 94.4 +/- 3.0 nmol/l on the two study days. The values were not correlated
      with age or level of fitness. The platelet [Ca+2]i was 99.2 +/- 4.2 nmol/l after
      exercise, not different from the resting values. Platelet activation with
      adrenaline and thrombin across a wide range of doses resulted in prompt increases
      in [Ca+2]i, which were 50% less in platelets after exercise than at rest (P <
      0.05). Activation with angiotensin (Ang) II, on the other hand, was less
      pronounced and less clearly influenced by exercise. We conclude that exercise
      influences the platelet activation state and reactivity. The decreased [Ca+2]i
      responses to adrenaline and thrombin suggest that [Ca+2]i stores were in part
      depleted at exercise compared to rest, an effect not observed with Ang II perhaps
      because of the smaller number of Ang II-operative receptors on platelets.

PMID- 8867564
TI  - Fibrinogen and the albumin-globulin ratio in essential hypertension: relations to
      plasma renin system activity.
AB  - The present study was designed to evaluate the blood albumin-globulin ratio and
      fibrinogen levels in untreated patients with essential hypertension according to
      their renin profile, and to investigate the relationship between these
      hemorheologic variables and metabolic cardiovascular risk factors. Patients with
      uncomplicated essential hypertension (n = 36, DBP = 95-115 mm Hg) were studied.
      Normotensive, age and sex matched volunteers (n = 19) served as controls.
      Assessment of plasma renin activity (PRA) related to concurrent 24 h sodium
      excretion was used to define patients with high (n = 12), medium (n = 16) and low
      renin profile (n = 8). Plasma fibrinogen levels and the albumin-globulin ratio (A
      G ratio) were determined. The A-G ratio was significantly lower (P < 0.05) in the
      high PRA group compared to the low renin group or the controls. The A-G ratio was
      significantly negatively related to PRA (r = -0.348; P = 0.043) and serum C
      peptide (r = -0.395; P = 0.017). Fibrinogen levels were lower (P < 0.05) in the
      controls when compared to high and medium PRA group. Fibrinogen was associated
      with total cholesterol (r = 0.479; P = 0.037), HDL cholesterol (r = -0.467; P =
      0.028), plasma triglycerides (r = 0.414; P = 0.012) and fasting plasma glucose
      level (r = 0.358; P = 0.032). In conclusion, essential hypertensive patients with
      high PRA display more pronounced alterations in blood proteins, particularly in
      the decrease of the A-G ratio than patients with low PRA. This may be one
      additional factor accounting for the higher incidence of cardiovascular disease
      previously reported in high PRA group.

PMID- 8867565
TI  - Effects of aging on left ventricular-arterial coupling in man: assessment by
      means of arterial effective and left ventricular elastances.
AB  - The ejection fraction (EF) is a load-dependent index of the systolic function of
      the left ventricle (LV), which depends on the 'functional' coupling of the LV
      with the arterial system, evaluated by the ratio between arterial effective
      elastance (Ea) to end-systolic left ventricular elastance. The spectrum of
      changes in LV and the arterial system during aging has not been studied by means
      of coupled analysis of elastances. Twenty-five normotensive healthy subjects aged
      from 22 to 68 years underwent hemodynamic and angiographic studies. The
      functional properties of the arterial system were evaluated in terms of Ea (end
      systolic pressure/stroke volume), and the systolic function of the LV was
      approximated by the end-systolic pressure to end-systolic volume ratio (Elv). The
      result is that Ea increased linearly with age. Elv increased less than Ea. The
      positive relationship between Ea/Elv and age was close to statistical
      significance (r = 0.39, p = 0.07), suggesting that left ventricular-arterial
      coupling changes little with aging. Analysis of the relationship between EF and
      end-systolic stress showed that several points were situated at the lower part of
      the relationship in elderly subjects, suggesting a decrease in the intrinsic
      contractility of left ventricular muscle in some cases. Aging is characterized by
      a simultaneous increase in arterial system elastance and the systolic performance
      of the left ventricular pump, thereby preserving the transfer function of the
      arterial system as a whole. However, some aged subjects may depart from this
      rule, probably because of variability in the capacity to produce myocardial
      hypertrophy and/or altered inotropy of the muscle.

PMID- 8867566
TI  - Quality of life in normotensives compared to hypertensive men treated with
      isradipine or methyldopa as monotherapy or in combination with captopril: the
      LOMIR-MCT-IL study.
AB  - Quality of life (QOL) measures were assessed in a multi-center, double-blind,
      case-controlled trial of 1 year's duration. A total of 368 hypertensive male
      patients were randomly assigned to monotherapies of either isradipine, methyldopa
      or placebo. If normotension was not achieved, captopril was added. QOL
      assessments in the hypertensives and in 155 normotensives included a self
      structured scale to measure the subjective perception of QOL, the severity,
      desirability and controllability of recent critical life events, semantic memory,
      physical dysfunction, sleep disorders, sexual difficulties, depression and work
      related stress. The overall withdrawal rate during the trial was 19%, mainly due
      to lack of efficacy and adverse experiences. At baseline, and at the end of the
      trial, the normotensives as compared to hypertensive patients, had significantly
      better scores in most QOL measures. Patients treated with the combination of
      isradipine and captopril reported more favorable changes in the subjective
      measure of QOL (P < 0.03) and in semantic memory (P < 0.001) than patients
      treated with any of the monotherapies or with methyldopa in combination with
      captopril. There were no statistically significant differences among treatments
      for changes of other indices of QOL. In most QOL measurements, normotensives
      rated better then hypertensives. Patients treated on long-term therapy with the
      combination of isradipine and captopril showed improvement in self-structured QOL
      measures and semantic memory, compared to patients treated either with methyldopa
      or placebo.

PMID- 8867567
TI  - Efficacy and tolerability of slow release urapidil (ebrantil) in hypertensive
      patients with non-insulin dependent diabetes mellitus (NIDDM).
AB  - Urapidil, a new alpha-blocker that peripherally antagonizes postsynaptic alpha 1
      receptors and centrally causes a reduction in sympathetic tone as agonist of the
      serotoninergic receptors, was assessed for its antihypertensive effect and its
      role on glucose and lipid metabolism and insulin sensitivity in diabetic
      hypertensive patients. Thirty-three non-insulin dependent diabetes mellitus
      (NIDDM) patients with diastolic blood pressure (BP) of 95-115 mm Hg were treated
      with either 30 or 60 mg urapidil twice a day, with a gradual increment up to a
      maximum of 90 mg b.i.d., in order to reduce diastolic pressure to < 90 mm Hg or
      by at least 10% in the sitting position. A significant reduction in systolic and
      diastolic arterial pressure, not accompanied by an increased heart rate, was
      achieved after 12 weeks of treatment. Lipid and carbohydrate homeostasis and
      glycemic control, as assessed by HbA1C levels, were not affected. The fasting
      insulin concentration before the glucose load remained similar, but there was a
      trend toward reduction in peak insulin concentration, and the ratio of insulin
      change to glucose change between fasting levels and peak levels was significantly
      lowered by treatment, suggesting improved insulin sensitivity. In conclusion,
      urapidil is an effective antihypertensive agent in NIDDM patients with essential
      hypertension, with a neutral effect on lipids and carbohydrates and a possible
      beneficial effect on insulin resistance.

PMID- 8867569
TI  - Characteristics of a reversed circadian blood pressure rhythm in pregnant women
      with hypertension.

PMID- 8867568
TI  - Once-daily monotherapy with trandolapril in the treatment of hypertension.
AB  - Once-daily antihypertensive drugs that control blood pressure (BP) for the full
      24-h dosing period, enhance patient compliance and may reduce the cardiovascular
      complications of hypertension which occur with increased frequency in the early
      morning. Since some once-daily agents are more effective than others in
      maintaining antihypertensive effects toward the end of the 24-h dosing interval
      this study was designed to evaluate the duration of antihypertensive action of
      trandolapril using 48 h ambulatory blood pressure monitoring (ABPM) in 41
      patients with mild-to-moderate essential hypertension. Twenty-four hour ABPM was
      performed on two consecutive days (48 h) after a 4 week single blind placebo run
      in period and repeated after an 8 week double-blind period during which 20
      patients were randomized to treatment with trandolapril (2-4 mg once-daily) and
      21 patients to matching placebo. During the second 48 h monitoring period,
      placebo rather than active medication was taken by both of the groups at the
      beginning of the second 24 h segment. Trandolapril reduced ambulatory systolic
      and diastolic BP by 9.4 and 6.2 mm Hg respectively (P < or = 0.01) during the
      first 24 h of the post treatment monitoring period while placebo increased the
      systolic and diastolic BPs in the same period by 3.8 and 2.6 mm Hg (P < 0.05).
      During the second monitoring period (hours 25-48), trandolapril reduced systolic
      and diastolic BP by 5.6 and 3.9 mm Hg while placebo increased BP by 2.3 and 1.6
      mm Hg (P < 0.03). When compared to placebo by 2 h time blocks, throughout the 2
      days of monitoring, trandolapril produced clinically significant decreases in
      systolic and diastolic BP for 30 and 28 h following dosing. This indicates that
      trandolapril can be considered a true once-daily antihypertensive agent.

PMID- 8867570
TI  - Character and psychotherapy.
AB  - Psychoanalytic theory of psychopathology began as a theory of particular
      pathogenic agents in the form of repressed memories or drive-generated fantasies.
      It has developed in the direction of a theory of the mind's organization; that
      is, a theory of character pathology. A characterological understanding of
      psychopathology enlarges therapeutic attention beyond the patient's verbal
      references and toward the patient himself in the "here and now."

PMID- 8867571
TI  - Love between therapist and patient: a review.
AB  - To avoid the passions of love and hate between them, therapists and patients
      construct and preserve negative barriers of angry criticism, dissatisfaction, and
      sadomasochism. This review aims to help therapists tolerate and work with loving
      feelings between patient and therapist for the benefit of the patient.

PMID- 8867572
TI  - Resistance viewed from different perspectives.

PMID- 8867573
TI  - Resistance: friend or foe?
AB  - This paper shows resistances in a benign light. The view is presented that
      psychoanalysts able to view resistances in a friendly light as challenges and
      guides, rather than as onerous roadblocks, experience maximum success for the
      patient and maximum satisfaction for themselves. The use of psychoanalytic
      technique to this end is demonstrated.

PMID- 8867574
TI  - An object relations perspective on the nature of resistance and therapeutic
      change.
AB  - An object relations model of resistance and therapeutic change based on
      Fairbairn's conception of psychopathology is presented in this paper. His
      recasting of the nature of the repressed in terms of malevolent inner objects is
      described. A clinical vignette is provided to illustrate the manner in which
      resistance to the therapeutic alteration of the patient's pathological internal
      object world can be surmounted by both interpretive work and the provision of a
      replacement good object (the therapist) in the treatment situation.

PMID- 8867575
TI  - Projective identification: a resistance in couples.
AB  - From an object relational perspective, couples are being viewed more and more as
      complex systems in which projective identificatory interactions are prevalently
      observable. The resistive aspect of the collusive arrangements established in
      couples becomes even more evident as the concept of projective identification is
      applied to understanding such relationships. By repeatedly confronting and
      exploring the unconscious role assignments and proxy evocations underlying couple
      resistances, the partners are encouraged to reclaim dissociated parts of
      themselves placed into the mate and to maturationally advance from the paranoid
      to the depressive position.

PMID- 8867576
TI  - The concept of resistance in self psychology.
AB  - Self psychology views resistances as protecting a vulnerable self. Resistances
      are seen as efforts to maintain levels of organization that patients have
      achieved within the context of their traumatic life situation. Patients feel able
      to move forward in the treatment when the importance of their need to maintain
      their developmental position is understood. This view is in contrast to the
      traditional view of resistances as treatment interferences that must be overcome
      as they defend against awareness of impulses and allow for unconscious
      instinctual gratification.

PMID- 8867577
TI  - Phenomena of resistance in modern group analysis.
AB  - The development of the concept of resistance is briefly traced. The contributions
      of Spotnitz and his coworkers to the broadening of the concept of the Modern
      Analytic approach of supporting and resolving reistance are delineated. The ways
      in which resistance is modified in the group setting are presented and
      illustrated by clinical vignettes of members resolving each other's individual
      resistances and engaging in group resistance. Group destructive resistances are
      identified and guidelines for minimizing their impact are offered.

PMID- 8867579
TI  - Mental Darwinism and the evolution of the emotion-processing mind.
AB  - The cognitive mental module with which humans process and adapt to emotionally
      charged environmental or triggering events is identified as the emotion
      processing mind. The current architecture of this mental module presents several
      anomalous features. In an effort to clarify their basis, the evolution of this
      module is traced for the 6,000,000-year history of hominid existence. In
      addition, the nature of its current adaptive resources are explored as a way of
      introducing mental Darwinism, the concept that the emotion-processing mind is an
      adaptive entity that operates according to the principles of universal Darwinism.

PMID- 8867578
TI  - Resistances in a hospital setting: issues in resolution.
AB  - This article describes multiple forms of resistances--patients toward reality,
      staff toward patients, staff toward staff, and my own counterresistances--in a
      hospital setting. Examples derive from within the psychiatric system itself,
      group work with a chronically ill population, a multiple family therapy group,
      and a case conference setting.

PMID- 8867580
TI  - Clinical use of B- and T-cell gene rearrangement analysis in hematopoietic
      disorders.
AB  - The clinical application of B- and T-cell gene rearrangement analysis is
      discussed relative to diagnostic problems in specific lymphoproliferative
      disorders. This article reviews the use of the Southern blot hybridization
      technique for B- and T-cell gene rearrangement detection in the analysis of
      various hematopoietic lesions. Several case studies are presented and analyzed.

PMID- 8867581
TI  - BCL-2 gene rearrangements in lymphoid malignancies.
AB  - Chromosomal translocations consistently associated with lymphoid malignancies
      result in gene rearrangements and activation of cellular oncogenes. The bcl-2
      gene rearrangement is one of the most thoroughly studied and clinically useful in
      the diagnosis and monitoring of patients with lymphoma. The molecular analysis of
      this gene rearrangement has led to the discovery of the first member of a new
      class of oncogenes, the regulators of programmed cell death.

PMID- 8867582
TI  - The role of molecular diagnostics in the clinical microbiology laboratory.
AB  - With the exquisite sensitivity, inherent specificity, and versatility of
      polymerase chain reaction (PCR) and other amplification techniques, it is clear
      that infectious disease diagnostic tests based on these methods will assume a
      niche quickly in many clinical microbiology laboratories. Routine implementation,
      however, requires that many issues be addressed, including control of amplicon
      contamination, specimen treatment to avoid inhibitors, interpretation of positive
      results when clinical significance is unclear, and cost. Laboratory experience
      with the Chlamydia Amplicor product (Roche Molecular Systems, Branchburg, NJ) is
      discussed to illustrate these issues. Commercial kit products using nucleic acid
      amplification techniques can be introduced into a routine laboratory easily and
      with a high degree of accuracy.

PMID- 8867583
TI  - Multiplex polymerase chain reaction for the diagnosis of sexually transmitted
      diseases.
AB  - Sexually transmitted diseases (STD) are a major cause of death worldwide.
      Traditional laboratory methods of culture and serology are giving way to new DNA
      technologies, especially nucleic acid amplification. To date, polymerase chain
      reaction (PCR) has been the most widely used amplification method. Multiplex PCR
      (M-PCR) is a modification of this technique that allows for the detection of DNA
      from several bacterial and viral STD in a single test. Over the next 5 years,
      several M-PCR tests will be introduced, affording the clinical laboratory
      improved diagnostic capabilities.

PMID- 8867584
TI  - DNA analysis in the study of fungal infections in the immunocompromised host.
AB  - Fungal infections, most of which are caused by the Candida species, are an
      increasing problem in the immunocompromised host. The clinical manifestations of
      Candida infections include disseminated candidiasis, oral and esophageal
      infections, focal hepatic infections, peritoneal urinary tract infections, and
      wound infections. DNA methods, which include pulse field electrophoresis and
      restriction enzyme analysis of genomic DNA, have been used to increase
      understanding of the epidemiology of these infections. These techniques have
      shown that most Candida infections are endogenous or acquired from one's own
      flora. Recent outbreaks have provided evidence for exogenous acquisition of some
      isolates. Better methods for differentiation of colonization versus infection and
      identifying infection in the absence of positive cultures are under
      investigation.

PMID- 8867585
TI  - NASBA: a novel, isothermal detection technology for qualitative and quantitative
      HIV-1 RNA measurements.
AB  - Although immunoassays have long served as the standard in the field of
      diagnostics, the advent of nucleic acid amplification technologies allows for a
      new array of diagnostic applications. NASBA, nucleic acid sequence-based
      amplification, is one such technology that is highly suited for the amplification
      of RNA. As such, NASBA is applied readily as a diagnostic tool for infectious
      diseases, particularly for RNA viruses, such as retroviruses. The development and
      application of NASBA technology as a qualitative and quantitative diagnostic
      system for HIV-1 are described in this article.

PMID- 8867586
TI  - The underlying molecular mechanism of apolipoprotein E polymorphism:
      relationships to lipid disorders, cardiovascular disease, and Alzheimer's
      disease.
AB  - Apolipoprotein E (apo E) polymorphism has important clinical correlates,
      including disorders of lipoprotein metabolism and atherosclerosis. This article
      provides a detailed methodology for apo E genotyping and discusses the link
      between apo E genotype and type III hyperlipoproteinemia, coronary heart disease
      (CHD), stroke, and Alzheimer's disease (AD). Although apo E genotype appears to
      provide significant information concerning the genetic component of CHD and AD
      risk, more research is needed before genotyping can be recommended as a routine
      screening tool. The data so far, however, implicate apo E as a major component of
      the genetic basis of cardiovascular disease and AD.

PMID- 8867587
TI  - Molecular approaches for the diagnosis of 21-hydroxylase deficiency and
      congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency results in
      deficiency of cortisol and aldosterone and overproduction of androgens. The 21
      hydroxylase locus has a complicated structure, with a highly homologous
      pseudogene (CYP21P) and an active gene (CYP21) in tandem repeats, a high degree
      of interindividual variation in gene copy numbers, and exchange of sequences
      between CYP21P and CYP21. Nine mutations, representing sequences that are
      normally present in the pseudogene, account for about 95% of all affected CYP21
      alleles. Accurate and rapid diagnostic evaluation of congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency can be performed by typing directly
      for disease-causing mutations using allele-specific polymerase chain reaction
      (PCR). A strong correlation exists between genotype and phenotype; mutational
      analysis can be used to predict disease severity in affected individuals.

PMID- 8867588
TI  - Risk assessment and presymptomatic molecular diagnosis in hereditary breast
      cancer.
AB  - Breast cancer susceptibility genes are being isolated at a rapid pace. Current
      molecular diagnostic techniques are being adapted to detect mutations in the
      germline and in tumors. The isolation of the breast and ovarian cancer gene 1
      (BRCA1) has brought about the potential for screening large numbers of
      individuals for genetically increased susceptibility to breast cancer. The
      advantages and limitations of presymptomatic testing are discussed.

PMID- 8867590
TI  - Forensic DNA tests.
AB  - DNA testing has revolutionized the forensic sciences. Forensic testing has
      continued to evolve, and now several methods are in use. The predominant methods
      of forensic DNA analysis are described, and their application in casework is
      summarized. The legal acceptance of this testing also is discussed.

PMID- 8867589
TI  - Resistance to activated protein C and a novel factor V gene mutation.
AB  - A novel mutation in the factor V gene of the blood coagulation cascade has been
      identified recently. The mutation confers a lifelong hypercoagulable state, and
      carriers of the mutation have an approximate eightfold increase in relative risk
      for the development of venous thrombosis. Carriers of the mutation manifest a
      laboratory coagulation defect termed resistance to activated protein C (APC).
      This article reviews the discovery of APC resistance, the identification of the
      factor V gene mutation, and laboratory approaches to their diagnosis.

PMID- 8867591
TI  - Gene therapy: a brief review.
AB  - Gene therapy is no longer defined simply as gene replacement; today, it is better
      defined as any treatment involving genetic alteration of cells. As a result, its
      applications have grown enormously and continue to do so. The purpose of gene
      therapy--treatment of the underlying cause of disease--represents a fundamental
      break with all previous forms of therapy in the history of medicine. Within a
      relatively short period, gene therapy promises to be a major pharmacologic force,
      revolutionizing the practice of medicine.

PMID- 8867592
TI  - Diagnostic molecular pathology in the twenty-first century.
AB  - Diagnostic molecular pathology is expanding rapidly with the aid of the Human
      Genome Project and the development of potentially user-friendly molecular
      diagnostic methods. The diagnostic molecular pathology laboratory of the future
      must be prepared to purify DNA or RNA from a variety of sources and to
      investigate the sequence of the target genome of interest using automated
      amplification and hybridization detection systems. There will be a shift in the
      emphasis from phenotypic to genotypic diagnosis, and the diagnostic molecular
      pathology laboratory of the early twenty-first century will perform 5% to 10% of
      the volume of all laboratory testing.

PMID- 8867593
TI  - Networking pathology services: adjusting to managed care.
AB  - Health care reform is creating the need for pathologists to find new approaches
      to providing traditional pathology services in an increasingly competitive
      environment. This article reviews changes impacting pathology practices and
      describes a "messenger network" model as a solution for pathology practices
      desiring to retain and increase market share.

PMID- 8867594
TI  - The hormonal control of testicular descent.
AB  - Descent of the testes is a complex event mediated by hormonal and mechanical
      factors. At present we hypothesize that testicular descent occurs as the result
      of the secretion of descendin from a normal testicle. Descendin secretion results
      in selective growth of the gubernacular cells. Gubernacular outgrowth results in
      masculinization of the inguinal canal. At the beginning of testicular descent,
      the patent processus migrates into the inguinal canal, transmitting
      intraabdominal pressure to the gubernaculum. The gubernaculum in turn applies
      traction to the testicle to introduce the testicle into the inguinal canal.
      Descent of the testes into and through the inguinal canal is an interplay between
      intraabdominal pressure transmitted by a patent processus vaginalis and androgen
      induced gubernacular regression. Specifically, we hypothesize that androgens
      under control of an intact fetal hypothalamic-pituitary axis alter the
      viscoelastic properties of the gubernaculum. Reductions in the turgidity of the
      gubernaculum allow intraabdominal pressure to push the testicle into the scrotum.
      Functional abnormalities in any of the above factors will result in
      cryptorchidism.

PMID- 8867595
TI  - Role of oxidative stress and antioxidants in male infertility.
AB  - Oxygen toxicity is an inherent challenge to aerobic life, including spermatozoa,
      the cells responsible for propagation of the species. How this toxicity affects
      the spermatozoan in its interactions with the ovum is still unknown. An increase
      in oxidative damage to sperm membranes, proteins, and DNA is associated with
      alterations in signal transduction mechanisms that affect fertility. Recent
      evidence suggests that spermatozoa and oocytes possess an inherent but limited
      capacity to generate ROS to aid in the fertilization process. Though a variety of
      defense mechanisms encompassing antioxidant enzymes (SOD, catalase, and GSH
      peroxidase and reductase), vitamins (E, C, and carotenoids), and biomolecules
      (GSH and ubiquinol) are available, a balance of the benefits and risks from ROS
      and antioxidants appears to be necessary for the survival and functioning of
      spermatozoa. An assay system for the evaluation of OSS needs to be developed.
      Such an assay will assist the clinician in the assessment of fertility status of
      both male and female partners. The determination of this OSS value will also
      theoretically identify the subgroups of responders and nonresponders to any
      putative antioxidant therapy. Though the therapeutic use of antioxidants appears
      attractive, clinicians need to be aware of exaggerated claims of antioxidant
      benefits by various commercial supplements for fertility purposes until proper
      multicenter clinical trial have been completed.

PMID- 8867596
TI  - Effect of TGF-beta 1, TGF-alpha, and EGF on cell proliferation and cell death in
      rat ventral prostatic epithelial cells in culture.
AB  - A tissue culture system for rat prostatic epithelial cells was developed, and the
      effect of epidermal growth factor (EGF), transforming growth factor alpha (TGF
      alpha), and transforming growth factor beta 1 (TGF-beta 1) on these cells was
      evaluated. The primary culture was prepared by DNAse/collagenase dissociation of
      minced ventral prostates. Cells were initially plated in RPMI-1640 medium
      containing 10% fetal bovine serum to allow the preferential attachment of stromal
      cells. Twenty-four hours later, the unattached epithelial cells were replated in
      WAJC-404 medium supplemented with insulin (5 micrograms/ml), transferrin (5
      micrograms/ml), and selenious acid (5 ng/ml). Bovine pituitary extract (BPE) (30
      micrograms/ml), EGF (10 ng/ml), and TGF-beta 1 (0, 0.1, and 1.0 ng/ml) were added
      either alone or in combination according to experimental requirements. The rate
      of cell proliferation was assessed by counting the total cell number and by
      [3H]thymidine incorporation. Prostatic epithelial cells exhibited a bell-shaped
      growth curve in a span of 7-8 days, with a growth peak at day 3 or 4 of culture.
      Treatment of cells with EGF or TGF-alpha resulted in a concentration-dependent
      increase in cell growth, whereas addition of TGF-beta 1 into the culture resulted
      in an inhibition of cell proliferation that could be reversed with increasing
      concentrations of EGF. Cell death was assessed using the terminal
      deoxynucleotidyl transferase (TdT)-mediated immunoperoxidase-digoxigenin nick end
      labeling technique and the trypan blue exclusion test. Epithelial cells cultured
      in media containing EGF had the lowest incidence of cell death. Cells cultured in
      the absence of EGF demonstrated a marked increase in cells undergoing cell death.
      The addition of TGF-beta 1 into the EGF-depleted medium caused a further increase
      of cell death. These results indicated that cell proliferation and cell death in
      rat prostatic epithelial cells in culture could be modulated by EGF and TGF-beta
      1. The former stimulated cell proliferation and prevented cell death, whereas the
      latter inhibited proliferation in the presence or absence of EGF and induced cell
      death.

PMID- 8867597
TI  - Impaired secretory function of the prostate in men with oligo-asthenozoospermia.
AB  - The secretory function of the human prostate and the seminal vesicles is a
      prerequisite for gel formation and liquefaction of semen, but the relation to
      poor sperm motility and low sperm count in infertile men remains to be clarifyed.
      Our aim was to evaluate the secretory function of the prostate and the seminal
      vesicles in normozoospermic men (n = 35) and in asthenozoospermic men, who were
      all also oligozoospermic (n = 27). All 62 subjects belonged to couples undergoing
      routine infertility evaluation. In liquefied seminal fluid we measured the
      concentrations of fructose and protein C inhibitor (PCI) contributed by the
      seminal vesicles, PCI complexed to prostate-specific antigen (PSA), and the
      prostatic contribution of zinc, PSA, acid phosphatase (PAP), beta
      microseminoprotein (beta-MSP), and Zn alpha 2-glycoprotein (Zn alpha 2-GP). The
      concentration of each prostatic secretory protein correlated significantly with
      that of zinc (P < 0.01) in both the normozoospermic (NZS) and oligo
      asthenozoospermic (OAZS) subgroups, but the PCI concentration did not correlate
      significantly with that of fructose. There was no significant difference between
      the NZS and OAZS subgroups in ejaculate volume or secretory contribution from the
      seminal vesicles, whereas the OAZS subgroup was characterized by significantly
      lower secretory contributions of Zn alpha 2-GP (P = 0.001), Zn, PSA, PAP (P <
      0.01), and beta-MSP (P < 0.05). The two subgroups did not differ significantly in
      the serum concentration of luteinizing hormone (LH), testosterone, or sex hormone
      binding globulin (SHBG). The results thus suggest the secretory contribution of
      major prostatic proteins and zinc per ejaculate to be significantly decreased in
      oligo-asthenozoospermic men. The importance of this finding in relation to poor
      sperm count and motility as indicators of impaired gonadal function requires
      further investigation.

PMID- 8867598
TI  - Testosterone and spermatogenesis: evidence that androgens regulate cellular
      secretory mechanisms in stage VI-VIII seminiferous tubules from adult rats.
AB  - The aim of this study was to investigate the effect of testosterone manipulation
      on the quantitative synthesis and secretion of a number of specific proteins
      produced by seminiferous tubules (ST) isolated at stages VI-VIII of the
      spermatogenic cycle from adult rats. The proteins selected were derived from
      different cellular sources. ST were isolated from control rats, from rats treated
      4 days earlier with ethane dimethane sulfonate (EDS) to induce complete
      testosterone withdrawal by the destruction of the Leydig cells, and from EDS
      treated rats injected with testosterone esters (TE) in order to maintain
      quantitatively normal spermatogenesis. Two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, combined with computerized image analysis,
      was used to analyze 35S-methionine-labeled intracellular and secreted proteins.
      Testosterone withdrawal did not affect to any significant degree the total
      synthesis of any of the proteins studied. Similarly, the secretion of the major
      known Sertoli cell proteins SGP-1 and SGP-2, together with a third putative
      Sertoli cell protein, all of which appeared to be secreted constitutively, was
      also not affected to any major degree by EDS treatment. In contrast, the
      secretion of another probable Sertoli cell protein, together with six proteins
      found to be secreted by germ cells and one protein that appeared to derive from
      more than one cellular source, was reduced dramatically by testosterone
      withdrawal, but was maintained by treatment with EDS+TE. All of the affected
      proteins appeared to be secreted in a regulated manner. Our results confirm that
      testosterone manipulation has little or no effect on either total protein
      synthesis by ST, or on the secretion of the major Sertoli cell secretory
      proteins, at stages VI-VIII of the spermatogenic cycle, but suggest strongly that
      testosterone regulation of ST protein secretion at these stages is mediated by an
      effect on the regulated secretory pathways. Our findings also demonstrate that
      the secretion, not only of Sertoli cell proteins, but also of those secreted by
      germ cells, is androgen-regulated.

PMID- 8867599
TI  - Androgen receptor immunoexpression in the testes of subfertile men.
AB  - The localization and intensity of androgen receptor immunostaining was studied in
      the testes of 37 subfertile men with oligozoospermia and normal serum
      gonadotropin levels using a polyclonal antibody raised against a synthetic
      peptide corresponding to the first 20 N-terminal amino acid residues of the
      androgen receptor (AR). Furthermore, we investigated whether or not the
      immunoexpression of the AR in human Sertoli cells, in histologically normal
      testis tissue, is dependent on the stage of the spermatogenic cycle, as has been
      found in the rat. In the human testis, AR immunoexpression was observed in
      Sertoli cells, peritubular myoid cells, Leydig cells, and periarteriolar cells,
      but not in germinal cells. We found no evidence for a stage-dependent
      immunoexpression of AR in Sertoli cells. The intensity of AR immunoexpression
      varied substantially between biopsy specimens of different patients. There was,
      however, no correlation of the intensity of AR immunoexpression in either Sertoli
      cells or peritubular myoid cells with spermatogenic adequacy as measured by the
      method of Johnsen. When, in this study, the intensity of peritubular myoid cell
      staining was used as a standard to evaluate the intensity of Sertoli cell
      staining, no correlation was detected as well. Furthermore, serum gonadotropin
      levels were not correlated with AR immunoexpression levels in Sertoli cells and
      peritubular myoid cells. These results indicate that immunodetectability of the
      AR is not related to the condition of the spermatogenic epithelium in patients
      with oligozoospermia. Inappropriate expression of the AR is neither a cause nor a
      consequence of idiopathic infertility in the present group of patients.

PMID- 8867600
TI  - Structure of the rRNA genes in the hamster sperm nucleus.
AB  - We have examined the structure of the major ribosomal RNA (rRNA) genes in the
      hamster sperm nucleus, using fluorescent in situ hybridization (FISH). The rRNA
      genes are present as tandemly repeated clusters located at the telomeric ends of
      the short arms of five pairs of acrocentric chromosomes in the Syrian golden
      hamster (as they are in humans). In somatic cells, these five chromosome pairs
      come together to form the nucleolus, the site of rRNA synthesis. The nucleolus
      remains intact through S phase of the cell cycle, breaking apart only during late
      G2 and mitosis when the chromosomes condense. Mammalian sperm nuclei are the
      final products of meiotic division and morphological differentiation that
      includes a dramatic chromatin condensation. Consequently, it was not immediately
      obvious whether the rRNA genes would be condensed into a nucleolus-like structure
      in the mature spermatozoa, or separated, as they are in mitotic chromosomes. We
      found that of 117 sperm nuclei examined, 91.5% contained between two and five
      FISH signals for the rRNA gene clusters, and 64.0% contained four (29%) or five
      (35%) signals. In decondensed hamster sperm nuclei, the rRNA hybridized signals
      were separated into independent strands. These data collectively indicate that
      the chromosomes containing the rRNA genes are not bound together into a pre
      nucleolar structure in fully condensed mammalian sperm nuclei.

PMID- 8867601
TI  - Synchronous assessment of sperm motility and fertilizing ability in the hamster
      following treatment with alpha-chlorohydrin.
AB  - To investigate the relationship between sperm motion parameters and fertilizing
      ability, a model was developed to assess both of these endpoints synchronously
      using a toxicant that inhibits sperm motion. alpha-Chlorohydrin (ACH) was
      administered daily for 4 days to male hamsters at 0, 33, 49, 66, and 83 mg/kg
      body weight. These males were then allowed a 45-minute breeding period with
      untreated estrus females on the morning of day 5. One hour after breeding, sperm
      samples were surgically recovered from the uteri of the females for motility
      analysis. Six hours later, eggs were flushed from the oviducts and evaluated for
      fertilization. Cauda epididymal sperm were also collected from the males shortly
      after breeding. Proportions of motile and progressively motile sperm were
      manually quantified, and overall sperm velocity and the velocity of
      representative vigorously swimming sperm in both the uterine and epididymal
      samples were measured by computer-aided sperm analysis. Significant decreases in
      in vivo fertilization rates and epididymal sperm motion parameters were observed
      at 66 and 83 mg/kg ACH, whereas uterine sperm motion was adversely affected at
      all ACH dosages used. All sperm motion parameters except the percentage of motile
      sperm in the epididymis were significantly correlated with fertilization rates by
      both linear and logistic regression. Overall, uterine and epididymal sperm
      endpoints predicted fertilizing ability comparably well. Stepwise multiple linear
      regression gave a model containing epididymal sperm velocity (EVCL) and uterine
      sperm percent motility (UMOT) with an R2 value of 0.649. Stepwise multiple
      logistic regression gave models containing EVCL alone and EVCL and UMOT in binary
      (fertile/infertile) and quantal models, respectively.

PMID- 8867602
TI  - Cryopreservation reduces the ability of equine spermatozoa to attach to oviductal
      epithelial cells and zonae pellucidae in vitro.
AB  - Two bioassays were used to evaluate the interaction of fresh and cryopreserved
      equine semen with oviductal epithelial cells (OEC) and with the zona pellucida
      (ZP). Split ejaculates were either stored at room temperature or frozen and
      thawed. In experiment 1, progressive motility and membrane integrity were
      evaluated for each treatment. Fluorescent labeled spermatozoa were cocultured
      with monolayers of OEC for 30 minutes, and the number of sperm attached to OEC
      was counted by fluorescence microscopy and analysis of digitized images. Motility
      of spermatozoa attached to OEC was observed at 0.5, 3, 6, 18, 24, and 48 hours
      after insemination. In experiment 2, progressive motility, membrane integrity,
      and acrosomal integrity were determined. Differential labeling with the
      fluorochromes fluorescein isothiocyanate (FITC) or tetramethylrhodamine
      isothiocyanate (TRITC) was used to distinguish fresh and frozen-thawed
      spermatozoa. Equal numbers of motile spermatozoa from each treatment were
      incubated with salt-stored equine oocytes for 4 hours, and the number of
      spermatozoa firmly bound to the ZP was counted using dual-wavelength
      epifluorescence microscopy. Fewer (P < 0.001) cryopreserved spermatozoa attached
      to OEC compared to spermatozoa stored at room temperature. The motility of
      spermatozoa attached to OEC decreased over time within each treatment group (P <
      0.001), but this decrease was not different between treatments. The mean number
      of spermatozoa bound per ZP and percentage of acrosome-intact spermatozoa were
      lower (P < 0.05) for frozen-thawed than for fresh spermatozoa. There was no
      effect of stallion on acrosomal status of frozen-thawed spermatozoa; however, the
      number of spermatozoa bound per ZP was different between stallions within
      treatments (P < 0.05). These results indicate that the ability of cryopreserved
      equine spermatozoa to attach to equine OEC or ZP in vitro is reduced compared to
      fresh extended spermatozoa due to changes other than a reduction in post-thaw
      motility or membrane integrity. The decreased ability of frozen-thawed
      spermatozoa to attach to OEC or to ZP could explain, in part, the reduced
      fertility of cryopreserved compared to fresh spermatozoa in the horse.

PMID- 8867603
TI  - Adherence patterns and DNA probe types of Escherichia coli isolated from
      diarrheal patients in China.
AB  - One hundred and seventy-two strains of Escherichia coli isolated from diarrheal
      patients in Beijing, P.R. China, were analyzed for plasmid DNA profile, HEp-2
      cell adherence ability and reactivity to 10 previously described DNA probes. They
      had not been recognized as pathogenic E. coli in China. Of the 110 strains
      tested, 76 (69%) contained one or multiple large plasmids. Of the 71 strains with
      the large plasmids 64 could adhere to HEp-2 cells. Of the 172 strains, 102
      (59.3%) were hybridized with at least one of the 10 probes. Of those, seven
      strains hybridized with enteroaggregative E. coli (EAggEC) probe. Their serotypes
      were O128 (two strains), O6 (one strain), and O111 (one strain). Three strains
      were untypable. Six and three strains were hybridized with enteropathogenic E.
      coli (EPEC) attaching and effacing genes (eae) or EPEC adherence factor (EAF)
      probe, respectively. Two non-O157: H7 strains hybridized with enterohemorrhagic
      E. coli (EHEC) probe. Seventy-two strains (41.9%) hybridized with shiga-like
      toxin 2 or 1 (SLT2 or SLT1) probes. Among the SLT1 or SLT2 probe-positive
      strains, 54 hybridized with invasive (INV) plasmid probe developed for
      identification of enteroinvasive E. coli (EIEC) and Shigella species. The INV and
      SLT probe-positive strains might represent a new variety of verotoxin-producing
      E. coli (VTEC).

PMID- 8867604
TI  - Cloning and sequencing of the spore germination gene of Bacillus megaterium ATCC
      12872: similarities to the NaH-antiporter gene of Enterococcus hirae.
AB  - The germination mutant TM-31 of Bacillus megaterium ATCC 12872, was isolated by
      transposon Tn917 insertional mutagenesis. Glucose, L-proline, L-leucine and KNO3
      germinated TM-31 poorly. The DNA in the region of the Tn917 insertion was cloned,
      and its nucleotide sequence determined. One major open reading frame was present
      on the cloned DNA. The hydrophobic protein encoded is presumably membrane
      associated. A homology search revealed that the gene encoded in the region of the
      Tn917 insertion is homologous to napA of Enterococcus hirae. napA codes for the
      NaH-antiporter. It is hypothesized that transport of cations must play an
      important role in spore germination in B. megaterium ATCC 12872.

PMID- 8867605
TI  - The trpF nucleotide sequence and its promoter analysis in Pseudomonas aeruginosa.
AB  - The nucleotide sequence of the gene for the phosphoribosyl anthranilate isomerase
      (PRAI) (trpF) in Pseudomonas aeruginosa was determined. The gene encoded a
      polypeptide of 211 amino acid residues and its initiation codon was UUG. Northern
      hybridization analysis showed only one transcript for trpF (about 700
      nucleotides). Primer extension analysis revealed three transcription start sites
      which were at positions 52, 55 and 57 bases upstream of the initiation codon. A
      highly GC-rich 9-base-pair inverted repeat with 5-base-pair spacing was found
      upstream of a putative Shine-Dalgarno sequence. This inverted repeat could form a
      23-nucleotide stem-loop structure in the transcript. Deletion of the inverted
      repeat slightly decreased the promoter activity of trpF. The presence of
      tryptophan had no effect on transcription of trpF.

PMID- 8867607
TI  - The prevalence of Listeria monocytogenes in the environment of dairy farms.
AB  - The prevalence of Listeria monocytogenes in the environment of dairy farms was
      surveyed from December 1993 to June 1994 in one city of Hokkaido. L.
      monocytogenes was isolated from 3 out of 5 farms investigated. Serovar 4b
      organism was isolated from the brain stem of a cow from one farm which was
      clinically diagnosed as having listeriosis. The same serovar of L. monocytogenes
      was also isolated from the rectal contents of a healthy cow, straw on the floor,
      straw in the barn, and silage scattered around the silo from the same farm. At
      another farm, with no reported cases of bovine listeriosis, serovar 1/2 organism
      was isolated from the same types of samples as the above mentioned farm except
      from straw on the floor. The difference in the isolation rates of the organism
      from straw on the floor between the two farms (22%:5/23 vs 0%:0/24) is considered
      to be caused by the different feeding methods of silage between the two farms.

PMID- 8867606
TI  - Detection and measurement of Staphylococcus epidermidis slime using an ELISA
      technique.
AB  - A polyclonal rabbit anti-serum against the strong slime-producing Staphylococcus
      epidermidis strain RP62A was absorbed with the slime-negative phase variant of
      this strain PV1 in order to remove not slime-specific antibodies. Using this
      antiserum we established an ELISA which enables detection of slime production in
      S. epidermidis extracts. The ELISA showed high absorbance when extracts from
      slime-positive strains (confirmed in the tissue culture tube test) were used as
      antigens. The high absorbance of slime-positive strains was greatly reduced by
      periodate oxidation of the extracts and was resistant to proteinase digestion
      suggesting that the detected antigen is composed of polysaccharides. In contrast
      to other rapid and simple laboratory detection methods for S. epidermidis slime,
      the slime-specific ELISA gave positive results in the presence of human serum.

PMID- 8867608
TI  - Kinetics of anti-mannan antibodies useful in confirming invasive candidiasis in
      immunocompromised patients.
AB  - In studying the anti-mannan antibodies longitudinally in serial serum samples of
      three immunocompromised patients, it was observed that anti-mannan antibodies
      started to increase shortly after the moment that cultures of deep-tissue sites
      became positive with Candida albicans. The mean anti-mannan antibody titers
      determined in a group of 36 immunocompromised patients with invasive candidiasis
      increased within two weeks after the probable onset of invasive candidiasis. In
      contrast, anti-mannan antibody levels in serial serum samples of 14
      immunocompromised patients who were only colonized with C. albicans remained
      stable or decreased over time. The HA test measuring the anti-mannan antibodies
      was 64% sensitive and 89% specific in determining invasive candidiasis. In
      contrast, antibodies specific for candidal cytoplasmic antigens or enolase alone
      were of little value in confirming invasive candidiasis in these
      immunocompromised patients.

PMID- 8867609
TI  - Demonstration of a heat-stable 120-kilodalton protein of Rickettsia japonica as a
      spotted fever group-common antigen.
AB  - Genomic libraries of Rickettsia japonica were cloned into an expression vector
      lambda gt11. A clone expressing a protein reactive with antiserum against 120
      kilodalton (kDa) proteins, a mixture of heat-modifiable and heat-stable
      polypeptides, was selected and designated as lambda Rj120-1. The expressed
      protein has a molecular mass of 180 kDa. Western immunoblotting demonstrated that
      the expressed protein was a fusion protein with beta-galactosidase. The antiserum
      against 120-kDa proteins was absorbed by the induced lysogen, resulting in the
      removal of reactivity to the heat-stable 120-kDa polypeptide. The antiserum
      against the expressed protein reacted with heat-stable 120- to 130-kDa
      polypeptides of spotted fever group (SFG) rickettsiae in addition to R. japonica.
      The findings indicated that the protein expressed from the cloned gene of R.
      japonica possessed the antigenicity group-common to SFG rickettsiae. Primers
      designed from the gene coding for R. conorii heat-stable 120-kDa protein
      (Schuenke, K.W., and Walker, D.H., Infect. Immun. 62: 904-909, 1994) and lambda
      gt11 lacZ gene amplified the lambda Rj120-1 DNA by the polymerase chain reaction
      (PCR). Analysis of restriction fragment length polymorphism (RFLP) of the PCR
      amplified products revealed that the cloned DNA corresponds to a portion of the
      gene coding for the heat-stable 120-kDa protein of R. conorii with 2,519
      nucleotides beginning at nucleotide 190 of the open reading frame. RFLP
      demonstrated that the cloned gene was highly homologous to the corresponding gene
      of R. conorii.

PMID- 8867610
TI  - Characterization of a toxin-deficient Clostridium perfringens strain, KZ1340.
AB  - Clostridium perfringens KZ1340, previously classified as Clostridium plagarum, is
      an isolate from Antarctic soil, and was identified as an alpha-, theta-, and
      kappa-toxin non-producing variant. On Southern hybridization, the variant was
      found to be defective in the pfoA (theta-toxin) gene, but the plc (alpha-toxin)
      and colA (kappa-toxin) genes were present on the same EcoRI fragment as in the
      standard strain, NCTC8237. Northern analysis revealed that mature plc mRNA was
      transcribed in KZ1340 though less efficiently than in NCTC8237, while no mature
      colA mRNA was present in KZ1340. After transformation of the pfoA and plc genes
      into the KZ1340 via shuttle vector, pJIR418, the pfoA gene was successfully
      expressed but the plc gene was not efficiently expressed, suggesting that in
      KZ1340 there is negative regulation of plc gene expression. Toxin-deficient C.
      perfringens KZ1340 might be a suitable host for expression analysis of the pfoA
      gene and other clostridial virulence genes, if expressed efficiently, because it
      produces a small amount of extracellular toxins.

PMID- 8867611
TI  - Isolation of Coxiella burnetii from children with influenza-like symptoms in
      Japan.
AB  - The prevalence of Coxiella burnetii antibodies was investigated by indirect
      immunofluorescence (IF) test in 55 paired sera (acute and convalescent phases) of
      school children who had influenza-like symptoms. Of the convalescent serum
      samples examined, 18 (32.7%) sera reacted positively to phase II antigen of C.
      burnetii. Coxiella-like organism was isolated from the sera of 13 children after
      injection of the 18 acute phase sera into mice. The organism was identified as C.
      burnetii by Giemsa staining and the IF antigen test of mouse spleen smears, the
      polymerase chain reaction (PCR) method, electron microscopic observations of the
      mouse spleen cells, and the IF antibody test of mouse sera. This is the first
      report of isolation of C. burnetii from serum specimens of children having
      influenza-like symptoms. The evidence that C. burnetii was isolated from people
      indigenous to Japan at a considerably high incidence suggested that C. burnetii
      may be widespread as a cause of influenza-like symptoms in Japan.

PMID- 8867612
TI  - Colorimetric assay system for screening antiviral compounds against hepatitis B
      virus.
AB  - A highly sensitive, rapid, and accurate assay system was developed for the in
      vitro evaluation of anti-hepatitis B virus (anti-HBV) agents. Chronic HBV
      producing HB611 cells were used in combination with immunoaffinity purification,
      polymerase chain reaction (PCR), and hybrid capture detection. HB611 cells were
      incubated with putative anti-HBV agents for 7 days in 96-well microtiter plates.
      HBV was purified from HB611 cell culture media using immunoaffinity purification.
      The HBV DNA was extracted, amplified with PCR, and assayed using a hybrid capture
      colorimetric method. This assay provided quantitative detection of extracellular
      HBV DNA from 25 microliters of cell culture media. Using the colorimetric method,
      we found that 50% effective concentration levels of several known anti-HBV agents
      (HPMPA, PMEDAP, PMEA and others) were similar to those reported in studies using
      Southern blot analysis. These results demonstrate that this new and easily
      automated colorimetric assay system can be used for the rapid and accurate
      assessment of anti-HBV compound selectivity.

PMID- 8867613
TI  - Previous enteric adenovirus infection does not protect against subsequent
      symptomatic infection: longitudinal follow-up of eight infants.
AB  - Eight infants followed longitudinally were found to have enteric adenovirus
      (EAdv) infections: in 5 infants with diarrhea and in 3 with no accompanying
      diarrhea. Sequential stool samples prior to EAdv infections were tested for
      adenovirus antigen, anti-adenoviral IgA and neutralizing antibodies to serotypes
      40, 41 and 2 in order to ascertain whether protection from symptoms was due to
      prior infection. No difference was found in the number of adenoviral infections
      among infants prior to their EAdv infections with or without accompanying
      diarrhea. However, in 3 of the 5 infants in whom EAdv infection was accompanied
      by diarrhea and 2 of 3 control infants, previous EAdv infections had occurred as
      detected by serotype-specific antibody rises.

PMID- 8867614
TI  - Murine humoral immune response against recombinant structural proteins of
      hepatitis C virus distinct from those of patients.
AB  - We examined the humoral immune response to recombinant structural proteins of
      hepatitis C virus (HCV) such as C, E1 and E2 in immunized mice. Mice showed high
      induction of antibodies against these three structural proteins. Conformational
      and/or linear epitopes of these regions showed high responses in mice. Comparison
      with patients revealed higher anti-E1 and anti-E2 responses in mice and 15
      immunoreactive peptides which are unique to mice, especially 11 peptides from the
      E2 region. The hydrophilic regions of these proteins were found to be the most
      immunogenic. Therefore, the murine immune system against recombinant E1 and E2
      glycoproteins was distinct from those of patients in natural infection, and may
      be a target to find protective activity against HCV infection.

PMID- 8867615
TI  - Airway interleukin-8 in elderly patients with bacterial lower respiratory tract
      infections.
AB  - We investigated the interleukin-8 (IL-8) levels and neutrophil numbers in the
      sputum of 9 elderly patients with lower respiratory tract infections, including
      Pseudomonas aeruginosa infection, before and after treatment with various
      antimicrobial agents. The IL-8 levels in sputum supernatants and the neutrophil
      numbers in sputum smears from 9 patients decreased significantly after the
      elimination of the causative respiratory pathogens. We also demonstrated that
      human recombinant IL-8 at a range of 6.25-25 ng/ml significantly enhanced
      opsonophagocytic killing of P. aeruginosa immunotype-1 strain by human
      neutrophils in the presence of a serotype-specific anti-lipopolysaccharide
      monoclonal antibody and fresh normal human serum. These data suggest that the
      level of IL-8 production in the airways of patients with lower respiratory tract
      infections is dependent on bacterial densities, and indicate the important role
      of IL-8 not only in neutrophil migration but also in opsonophagocytic killing of
      bacteria in the lower respiratory tract.

PMID- 8867616
TI  - Who is responsible for good oral health?
AB  - The nation's oral health is improving, but I believe the gains are tardy,
      particularly among children. The Government declares that primary responsibility
      for good health lies with the individual, but one third of the population cannot
      undertake it. Speedier advance in oral health requires giving first place to
      society's (government's) role.

PMID- 8867617
TI  - Evidence based dentistry.

PMID- 8867618
TI  - Lower third molars and mandibular angle fractures.

PMID- 8867619
TI  - Florida dental AIDS mystery.

PMID- 8867620
TI  - A qualitative investigation of factors governing dentists' treatment
      philosophies.
AB  - The day to day decisions made by general dental practitioners have a significant
      influence on the oral health of the population, and yet are often poorly
      understood. This paper describes a qualitative study which sought to identify
      issues, other than the extent of pathology, which impinge upon dentists'
      restorative treatment decision making. It also aimed to develop a classification
      of these issues. Content analysis of in-depth interviews with 20 randomly
      selected general dental practitioners delineated 10 broad areas of concern. While
      each of these topics may influence a treatment decision to a greater or lesser
      degree, the issues relating to treatment planning can be divided into a
      classification which involves patient, profession and practitioner
      characteristics. This study indicates that an understanding of disease processes
      and of available treatment options is an insufficient basis for treatment
      decision making, as many considerations outside these straightforward concepts of
      health are brought to bear on decisions made within the dental surgery.

PMID- 8867621
TI  - Margin design for porcelain fused to metal restorations which extend onto the
      root.
AB  - A 90 degree shoulder is probably the most commonly used margin design for
      porcelain fused to metal (PFM) restorations. However, this design requires the
      removal of a significant amount of tooth tissue to provide a predictable
      restoration. This increases the risk of irreversible damage to the pulp,
      particularly if little tooth tissue is present, for example on exposed roots. In
      these situations more conservative designs, such as the 135 degree shoulder or
      deep chamfer, should be considered. Ideally these designs should be used with an
      all-metal margin since this is associated with the most predictable marginal
      seal. Where an all metal margin is aesthetically unacceptable a porcelain butt or
      subgingival margin can be considered. Newer techniques, such as resin bonded
      crowns, which minimise tooth destruction and provide acceptable aesthetics may be
      a viable alternative to traditional PFM restorations. Unfortunately, these newer
      techniques have not been evaluated long-term.

PMID- 8867622
TI  - Dental demands of older people living at home in Hertfordshire: changes over a 10
      year period.
AB  - A random sample of 300 subjects aged 65 and over, living at home in
      Hertfordshire, was interviewed to establish whether any changes in their oral
      status had arisen since a previous survey 10 years earlier. Results show that
      considerable improvements have taken place. The level of perceived need has
      fallen by about one-third, there has been a large fall in the proportion who are
      edentulous and a marked increase in the percentage of those with 10 or more
      natural teeth. Those with dentures are replacing them more frequently.

PMID- 8867623
TI  - Bilateral mandibular nerve damage following root canal therapy.
AB  - A case of bilateral inferior dental nerve paraesthesia following accidental
      introduction of root canal filling material into the canal is described. The
      significance of early recognition of the complication and prompt surgical
      intervention is highlighted.

PMID- 8867624
TI  - Centenary year of scientific papers in the British Dental Journal.
AB  - N J Ainsworth, in his paper on mottled teeth, published in 1933, was the first
      person in the UK responsible for identifying the presence of fluoride in water
      supplies and quantifying the amount of caries in areas with mottled teeth. As
      well as a brief summary of the paper by Mike Grace, John Murray writes a critical
      examination of this landmark paper.

PMID- 8867625
TI  - Results of the 1995 readers' survey.
AB  - Following a survey of BDJ readers in 1992 the BDJ was redesigned and relaunched.
      In mid-1995 a follow-up survey was conducted. Its findings show big improvements
      in readers' assessment of the design, style and content of the journal.

PMID- 8867626
TI  - Occluded fronts and double joints.

PMID- 8867627
TI  - Unexpected enhancement of beta-lactam antibiotic formation in Streptomyces
      clavuligerus by very high concentrations of exogenous lysine.
AB  - L-Lysine is known to stimulate production of beta-lactam antibiotics by
      Streptomyces clavuligerus via provision of the lysine breakdown product, L-alpha
      aminoadipic acid, which is a limiting precursor. Previous investigations utilized
      levels of 10-20 mM L-lysine as an addition to chemically-defined media resulting
      in 50-100% improvement in antibiotic production. We were surprised to note that
      as the concentration was further increased, the organism responded by producing
      even higher titers of antibiotics. The optimum concentration of 100 mM L-lysine
      yielded an approximate 500% increase in production with only minor effects on
      growth. DL- and D-Lysine also exerted enhancements suggesting the presence of a
      lysine racemase or some other route from D-lysine to L-alpha-aminoadipate in this
      organism; D-lysine was considerably less potent than DL- or L-lysine.

PMID- 8867628
TI  - Fed-batch fermentation with and without on-line extraction for propionic and
      acetic acid production by Propionibacterium acidipropionici.
AB  - Fed-batch propionic and acetic acid fermentations were performed in semi-defined
      laboratory medium and in corn steep liquor with Propionibacterium acidipropionici
      strain P9. On average, over four experiments, 34.5 milligrams propionic acid and
      12.8 milligrams acetic acid were obtained in about 146 h in laboratory medium
      with 79 milligrams glucose added over five feeding periods. The highest
      concentration of propionic acid, 45 milligrams, was obtained when the glucose
      concentration was not allowed to drop to zero. In corn steep liquor 35 milligrams
      propionic acid and 11 milligrams acetic acid were produced in 108 h from 59.4
      milligrams total lactic acid provided as seven feedings of corn steep liquor.
      Extractive fed-batch fermentations were conducted in semi-defined medium using
      either flat-sheet-supported liquid membranes or hollow-fiber membrane extraction
      to remove organic acids from the culture medium. As operated during the course of
      the fermentation, these systems extracted 25% and 22% of the acetic acid and
      36.5% and 44.5% of the propionic acid, respectively, produced in the
      fermentation. Total amounts of acids produced were about the same as in
      comparable nonextractive fermentations: 30-37 milligrams propionic acid and 13
      milligrams acetic acid were produced in 150 h. Limitations on acid production can
      be attributed to limited substrate feed, not to failure of the extraction system.

PMID- 8867629
TI  - Production of proteinase A by Saccharomyces cerevisiae in a cell-recycling
      fermentation system: experiments and computer simulations.
AB  - Overproduction of proteinase A by recombinant Saccharomyces cerevisiae was
      investigated by cultivations in a cell-recycling bioreactor. Membrane filtration
      was used to separate cells from the broth. Recycling ratios and dilution rates
      were varied and the effect on enzyme production was studied both experimentally
      and by computer simulations. Experiments and simulations showed that cell mass
      and product concentration were enhanced by high ratios of recycling. Additional
      simulations showed that the proteinase A concentration decreased drastically at
      high dilution rates and the optimal volumetric productivities were at high
      dilution rates just below washout and at high ratios of recycling. Cell-recycling
      fermentation gave much higher volumetric productivities and stable product
      concentrations in contrast to simple continuous fermentation.

PMID- 8867630
TI  - Microbial oxidation of ebastine.
AB  - The microbial oxidation of ebastine to carebastine was investigated. Among the 15
      micro-organisms examined, only the Cunninghamella strains showed the desired
      biotransformation. Cunninghamella blakesleeana oxidised the substrate within 7
      days, via the intermediates alcohol and aldehyde, mainly to carebastine, the
      corresponding carboxylic acid. Optimisation of the culture conditions increased
      the yield from initially 10% up to a reproducible 40%. For the synthesis of
      carebastine a substrate concentration of 200 mg/l, a starting pH of 5.0 and the
      addition of 1% poly(vinyl alcohol) is favourable. The results achieved in
      experiments with shaking flasks are transferable to the fermentation scale and
      yielded 270 mg carebastine in a 3-1 fermentation of 600 mg ebastine. The progress
      of the reaction was detected by TLC and HPLC, the products were identified by
      mass spectrometry and NMR.

PMID- 8867631
TI  - Improved delivery of biocontrol Pseudomonas and their antifungal metabolites
      using alginate polymers.
AB  - Alginate polymer was evaluated as a carrier for seed inoculation with a
      genetically modified strain Pseudomonas fluorescens F113LacZY, which protects
      sugar-beet against Pythium-mediated damping-off. F113LacZY survived in alginate
      beads at 5 log10 CFU/bead or higher counts for 8 weeks of storage, regardless of
      the conditions of incubation. In plant inoculation experiments, colonisation of
      the growing area of the root by F113LacZY, derived from alginate beads placed in
      the soil next to the seed or from an alginate coating around the seeds, was
      improved compared with application of just free cells of the strain. F113LacZY
      trapped in alginate beads was an effective producer of antifungal phloroglucinols
      as indicated by direct HPLC quantification of phloroglucinols and in vitro
      inhibition of both the indicator bacterium Bacillus subtilis A1 and the
      pathogenic fungus Pythium ultimum. Alginate polymer represents a promising
      carrier for the delivery of biocontrol inoculants for root colonisation and
      production of antifungal metabolites.

PMID- 8867632
TI  - Purification and characterization of a truncated Bacillus subtilis alpha-amylase
      produced by Escherichia coli.
AB  - A Bacillus subtilis amylase gene was inserted into a plasmid which was
      transferred to Escherichia coli. During cloning, a 3' region encoding 171 carboxy
      terminal amino acids was replaced by a nucleotide sequence that encoded 33 amino
      acid residues not present in the indigenous protein. The transformed cells
      produced substantial amylolytic activity. The active protein was purified to
      apparent homogeneity. Its molecular mass (48 kDa), as estimated in sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis, was lower than the molecular mass
      values calculated from the derived amino acid sequences of the B. subtilis
      complete alpha-amylase (57.7 kDa) and the truncated protein (54.1 kDa). This
      truncated enzyme form hydrolysed starch with a Km of 3.845 mg/ml. Activity was
      optimal at pH 6.5 and 50 degrees C, and the purified enzyme was stable at
      temperatures up to 50 degrees C. While Hg2+, Fe3+ and Al+3 were effective in
      inhibiting the truncated enzyme, Mn2+ and Co2+ considerably enhanced the
      activity.

PMID- 8867633
TI  - Reduction of growth and acetyl-CoA carboxylase activity by expression of a
      chimeric streptavidin gene in Escherichia coli.
AB  - The streptavidin gene from Streptomyces avidinii was expressed in E. coli as a
      non-fusion protein and as a glutathione S-transferase fusion protein. The
      streptavidin protein accumulated primarily in the inclusion bodies and did not
      alter cell growth. In contrast, the glutathione-S-transferase-streptavidin fusion
      protein was soluble. Nondenaturing polyacrylamide gel electrophoresis indicated
      that the chimeric glutathione-S-transferase-streptavidin protein was present
      mostly as a monomer, with some detectable polymeric forms. Cells grown in the
      presence of [3H]-biotin had label specifically associated with the expressed
      glutathione-S-transferase-streptavidin fusion protein, indicating this protein
      bound biotin in vivo. The majority of the radiolabeled biotin was associated with
      polymeric forms of the glutathione-S-transferase-streptavidin protein. The growth
      rates of biotin auxotrophs of E. coli growing in biotin-deficient media were
      substantially decreased by the expression of the glutathione-S-transferase
      streptavidin gene. The decreased growth rate correlated with a decrease in acetyl
      CoA carboxylase activity.

PMID- 8867634
TI  - A novel heterologous gene expression system in Saccharomyces cerevisiae using the
      isocitrate lyase gene promoter from Candida tropicalis.
AB  - We have found that the upstream region of the isocitrate lyase gene (UPR-ICL)
      from the n-alkane-utilizing yeast Candida tropicalis was functional in
      Saccharomyces cerevisiae as a novel promoter with nonfermentable carbon sources,
      such as oleic acid, acetate, ethanol, and glycerol/lactate. The expression of two
      foreign genes coding for beta-galactosidase from Escherichia coli (LacZ) and
      glutamate decarboxylase from rat brain was carried out under the control of UPR
      ICL. Expression of LacZ was repressed by glucose and enhanced over 300-fold by
      acetate. When an expression vector pWI3 containing multicloning sites between UPR
      ICL and the transcriptional terminator of the isocitrate lyase gene (TERM-ICL)
      was used, the smaller isoform of glutamate decarboxylase (GAD65) was highly
      produced in a soluble and active form. These results demonstrate that the novel
      expression system using UPR-ICL and TERM-ICL from C. tropicalis is useful for the
      production of heterologous proteins in S. cerevisiae.

PMID- 8867636
TI  - Overexpression of the gene for N-acylamino acid racemase from Amycolatopsis sp.
      TS-1-60 in Escherichia coli and continuous produciton of optically active
      methionine by a bioreactor.
AB  - A DNA sequence encoding N-acylamino acid racemase (AAR) was inserted downstream
      from the T7 promoter in pET3c. The recombinant plasmid was introduced into
      Escherichia coli MM 294 lysogenized with a bacteriophage lambda having a T7 RNA
      polymerase gene. The amount of AAR produced by the E. coli transformant was 1100
      fold more than that produced by Amycolatopsis sp. TS-1-60, the DNA donor strain.
      The AAR was purified to homogeneity from the crude extract of the E. coli
      transformant by two steps: heat treatment and Butyl-Toyopearl column
      chromatography. Bioreactors for the production of optically active amino acids
      were constructed with DEAE-Toyopearl-immobilized AAR and D- or L-aminoacylase. D-
      or L-methionine was continuously produced with a high yield from N-acetyl-DL
      methionine by the bioreactor.

PMID- 8867635
TI  - DNA sequence analysis, expression, distribution, and physiological role of the
      Xaa-prolyldipeptidyl aminopeptidase gene from Lactobacillus helveticus CNRZ32.
AB  - Lactobacillus helveticus CNRZ32 possesses an Xaa-prolyldipeptidyl aminopeptidase
      (PepX), which releases amino-terminal dipeptides from peptides containing proline
      residues in the penultimate position. The PepX gene, designated pepX, from Lb.
      helveticus CNRZ32 was sequenced. Analysis of the sequence identified a putative
      2379-bp pepX open-reading frame, which encodes a polypeptide of 793 amino acid
      residues with a deduced molecular mass of 88,111 Da. The gene shows significant
      sequence identity with sequenced pepX genes from lactic acid bacteria. The
      product of the gene contains a motif that is almost identical with the active
      site motif of the serine-dependent PepX from lactococci. The introduction of pepX
      into Lactococcus lactis LM0230 on either pGK12 (a low-copy-number plasmid vector)
      or pIL253 (a high-copy-number plasmid vector) did not result in a significant
      increase in PepX activity, while the introduction of pepX into CNRZ32 on pGK12
      resulted in a four-fold increase in PepX activity. Southern hybridization
      experiments revealed that the pepX gene from CNRZ32 is well conserved in
      lactobacilli, pediococci and streptococci. The physiological role of PepX during
      growth in lactobacillus MRS (a rich medium containing protein hydrolysates along
      with other ingredients) and milk was examined by comparing growth of CNRZ32 and a
      CNRZ32 PepX-negative derivative. No difference in growth rate or acid production
      was observed between CNRZ32 and its PepX-negative derivative in MRS. However, the
      CNRZ32 PepX-negative derivative grew in milk at a reduced specific growth rate
      when compared to wild-type CNRZ32. Introduction of the cloned PepX determinant
      into the CNRZ32 PepX-negative derivative resulted in a construct with a specific
      growth rate similar to that of wild-type CNRZ32.

PMID- 8867637
TI  - Bioremediation of 2,4,6-trinitrotoluene-contaminated soils by two different
      aerated compost systems.
AB  - Two composting systems were compared on a laboratory scale as a bioremediation
      technology for degradation or immobilization of 2,4,6-trinitrotoluene (TNT) in
      contaminated soils. The first compost was aerated from the beginning whereas the
      second compost was only aerated after an anaerobic prephase of 65 days. In the
      first compost system the TNT concentration declined rapidly by 92% but, at the
      end, TNT could be partially recovered. During the anaerobic prephase of the
      second compost system, TNT was almost completely converted to
      aminodinitrotoluenes, which during the subsequent aeration almost entirely
      disappeared. In addition, the second compost generated less toxic material than
      the first one as confirmed by inhibition of bioluminescence of Vibrio fischeri.
      These data show that microbiological TNT-degradation systems can be successfully
      designed which are prerequisite for an efficient bioremediation of contaminated
      soils.

PMID- 8867638
TI  - Anaerobic dechlorination and mineralization of pentachlorophenol and 2,4,6
      trichlorophenol by methanogenic pentachlorophenol-degrading granules.
AB  - Anaerobic granules developed for the treatment of pentachlorophenol (PCP)
      completely mineralized 14C-labeled PCP to 14CH4 and 14CO2. Release of chloride
      ions from PCP was performed by live cells in the granules under anaerobic
      conditions. No chloride ions were released under aerobic conditions or by
      autoclaved cells. Addition of sulfate enhanced the initial chloride release rate
      and accelerated the process of mineralization of 14C-labeled PCP. Addition of
      molybdate (10 mM) inhibited the chloride release rate and severely inhibited PCP
      mineralization. This suggests involvement of sulfate-reducing bacteria in PCP
      dechlorination and mineralization. Addition of 2-bromoethane sulfonate slightly
      decreased the chloride release rate and completely stopped production of 14CH4
      and 14CO2 from [14C]PCP. 2,4,6-trichlorophenol was observed as an intermediate
      during PCP dechlorination. On the basis of experimental results, dechlorination
      of 2,4,6-trichlorophanol by the granules was conducted through 2,4
      dichlorophenol, 4-chlorophenol or 2-chlorophenol to phenol at pH 7.0-7.2.

PMID- 8867640
TI  - Influence of a supplementary carbon source on biodegradation of pyridine by
      freely suspended and immobilized Pimelobacter sp..
AB  - The effect of the presence of supplementary glucose or acetate on the growth and
      pyridine-degrading activity of freely suspended and calcium-alginate-immobilized
      Pimelobacter sp. was investigated. Although the supplementary carbon sources
      could be degraded simultaneously with pyridine, Pimelobacter sp. exhibited a
      preference for pyridine over supplementary carbon sources. Thus, the pyridine
      degrading activity of the freely suspended cells was not decreased significantly
      by the addition of either glucose (1.5-6 mM) or acetate (6-24 mM) to the pyridine
      (6-24 mM). In the semi-continuous immobilized cell culture, immobilized cells
      also exhibited a preference for pyridine over supplementary carbon sources and
      did not switch their substrate preference throughout the culture. Owing to a high
      cell concentration, the volumetric pyridine degradation rate at 24 mM pyridine in
      the immobilized cell culture was approximately six times higher than that in the
      freely suspended cell culture. Furthermore, the immobilized cells could be reused
      16 times without losing their pyridine-degrading activity during the culture
      period tested. Taken together, the use of immobilized Pimelobacter sp. for the
      degradation of pyridine is quite feasible because of the preference for pyridine
      over supplementary carbon sources, the high volumetric pyridine degradation rate,
      and the reusability of immobilized cells.

PMID- 8867639
TI  - Activation and degradation of benzoate, 3-phenylpropionate and crotonate by
      Syntrophus buswellii strain GA. Evidence for electron-transport phosphorylation
      during crotonate respiration.
AB  - A strictly anaerobic, benzoate-degrading bacterium, Syntrophus buswellii strain
      GA, was able to degrade benzoate or 3-phenylpropionate to acetate, CO2 and H2, if
      the hydrogen partial pressure was sufficiently low. The hydrogen was removed in
      syntrophic coculture by Methanospirillum hungatei or by Desulfovibrio sp. through
      interspecies hydrogen transfer or in pure culture by the use of crotonate as
      reducible cosubstrate. Alternatively, S. buswellii strain GA could grow in pure
      culture with crotonate. Activities of seven catabolic enzymes were measured in
      crude cell extracts of S. buswellii strain GA grown with various substrates and
      of crotonate-grown S. buswellii strain DSM 2612A. Benzoate, 3-phenylpropionate
      and crotonate were activated by CoA ligases. Glutaryl-CoA dehydrogenase was found
      to be involved in the degradation of aromatic compounds and enzymes catalysing
      beta-oxidation were involved in the reaction sequence from crotonyl-CoA to
      acetate. A c-type cytochrome was present in the cytoplasm, whereas b-type
      cytochromes were associated with the membranes of both S. buswellii strains grown
      on crotonate. These indicated the presence of an electron-transport system. A
      high growth yield of crotonate-grown S. buswellii strain GA might be explained by
      electron-transport phosphorylation in addition to substrate-level
      phosphorylation.

PMID- 8867641
TI  - Changes in the composition of extracellular polymeric substances in activated
      sludge during anaerobic storage.
AB  - Changes in the chemical composition of organic compounds in total activated
      sludge, activated sludge extracellular polymeric substances (EPS), and sludge
      bulk water during anaerobic storage (12 days) were studied. The background for
      the study was that anaerobic storage of activated sludge, which often takes place
      at wastewater treatment plants before dewatering, causes a deterioration of the
      dewaterability. The reasons are not known at present, but may be related to
      changes in exopolymer composition of the flocs. The results showed that a fast
      decrease in total sludge protein and carbohydrate took place within 3 days of
      anaerobic storage as a result of degradation processes, which accounted for
      approximately 20% of the organic fraction. The amount of uronic acids and humic
      compounds remained almost constant in the sludge. The EPS were extracted from the
      floc matrix using a cation-exchange resin. In the EPS matrix a similar initial (2
      3 days) degradation of proteins and carbohydrate took place, whereas the content
      of DNA and uronic acids showed minor changes. The extractability of humic
      compounds increased during the first 3 days of storage. No changes in
      extractability of the carbohydrate were observed. A fraction of the EPS protein
      was found to be difficult to extract but was observed to be degraded during the
      anaerobic storage. The EPS composition was further characterized by high
      performance size-exclusion chromatography analysis obtained by on-line UV
      detection and post-column detection of proteins, carbohydrates, humic compounds
      and DNA. Four fractions of polysaccharides were found, of which only one was
      responsible for the decrease in the carbohydrate content observed with storage
      time. The fraction was presumably of low molecular mass. Humic compounds and
      volatile fatty acids (acetate and propionate) were released to the bulk water
      from the flocs during the storage. A possible mechanism to explain the reduced
      dewaterability developed during anaerobic storage, partly because of the observed
      changes in EPS, is discussed.

PMID- 8867642
TI  - A controlled clinical investigation of 3% diclofenac/2.5% sodium hyaluronate
      topical gel in the treatment of uncontrolled pain in chronic oral NSAID users
      with osteoarthritis.
AB  - Topical application, 4 times daily for 2 weeks, of the diclofenac-hyaluronan gel
      to 59 osteoarthritis patients induced a significantly greater (p = 0.057)
      analgesic effect than placebo gel lacking the active substance applied to 60
      control patients.

PMID- 8867643
TI  - The effect of hyaluronan on the in vitro deposition of diclofenac within the
      skin.
AB  - Hyaluronan is a glycosaminoglycan and has a protective, shock-absorbing and
      structure-stabilizing role in connective tissue. Recently, it has been suggested
      that hyaluronan can be used as a controlled and localized delivery vehicle for
      diclofenac in the treatment of a variety of conditions including osteoarthritic
      pain, basal cell carcinoma and actinic keratosis. The aim of this study was to
      examine the effects of hyaluronan on the in-vitro diffusion and deposition of
      diclofenac within the skin. The studies involved full thickness, epidermal sheet
      and stratum corneum human skin sections in an in-vitro Franz cell model, in which
      the diffusion and deposition of 14C-labelled diclofenac and 3H-labelled
      hyaluronan was investigated. The results showed that the diffusion of 14C
      labelled diclofenac was sustained and controlled by hyaluronan as compared to a
      buffer control, that a depot or reservoir of the drug was formed in the epidermis
      and that it was probably this layer that determined the rate of release of
      diclofenac within the skin. 3H-labelled hyaluronan was found to penetrate all
      layers of the skin, although the rate of diffusion was much slower than that of
      labelled diclofenac. Again, most of the activity was found to be retained within
      the epidermis, which supports the hypothesis of the importance of this layer in
      the mode of action. The presence within the epidermis of potential receptors for
      hyaluronan has recently been confirmed, and this may partially explain the
      findings of the present in-vitro studies.

PMID- 8867644
TI  - The role of hyaluronan and its receptors in restenosis after balloon angioplasty:
      development of a potential therapy.
AB  - Atherosclerosis is a progressive condition that is initiated by endothelial
      injury, promoted by growth factors, and which results in the formation of
      fibrofatty plaques that narrow the affected blood vessel. Balloon angioplasty is
      used to dilate these plaques in the coronary circulation so as to prevent
      occlusion of this critical blood supply. However, 30-50% of balloon dilatations
      end in restenosis within six months of the procedure. The pathogenesis of both
      atherosclerosis and restenosis after balloon angioplasty involves the migration
      of medial smooth-muscle cells across the internal elastic lamina to form a
      neointima. Proliferation of these cells and their elaboration of an extracellular
      matrix results in stenosis of the affected area. Investigation of several animal
      models, as well as of the human condition, indicates the presence of an ongoing
      inflammatory reaction involving T cells and other leukocytes which probably
      maintain smooth-muscle cell migration, proliferation and matrix deposition. We
      have shown that the stenotic response involves the expression of HA (hyaluronan)
      receptors on both the infiltrating white cells and on smooth-muscle cell
      populations. Thus, in vitro, the locomotion and chemotaxis of these cells in
      response to injury is inhibited by reagents that block HA-receptor interactions
      including HA-binding peptides and high doses of HA. Further, the expression of
      these HA receptors is up-regulated after balloon-catheter injury of the rat
      carotid artery, and exposure of injured arteries to high concentrations of HA in
      vivo results in significant inhibition of neointimal formation. The possible
      clinical benefits of this response are discussed.

PMID- 8867645
TI  - Hyaluronan as a drug delivery system for diclofenac: a hypothesis for mode of
      action.
AB  - Hyaluronan (HA) in combination with diclofenac is currently undergoing clinical
      trials as a topical preparation in the management of osteoarthritic pain, basal
      cell carcinoma and actinic keratosis. These are clearly diverse pathologies, but
      in all cases substance P plays a central role either directly or through
      secondary mediators such as prostaglandin E2 and nitric oxide. A common mechanism
      for HA in combination with diclofenac in these conditions may be through
      ameliorating the direct and indirect effects of substance P. Additionally, HA
      appears to depot and hold diclofenac in the epidermis, thereby prolonging its
      pharmacokinetic half-life. In rabbits, stenosis following balloon angioplasty is
      prevented by a subcutaneous dose of HA, probably through blockade of cell-surface
      HA receptors (ICAM-1, CD44 & RHAMM). The physicochemical properties of HA, and
      the binding of HA to HA receptors, suggests that HA will have value as a novel
      drug delivery system.

PMID- 8867646
TI  - The modulation of granulomatous tissue and tumour angiogenesis by diclofenac in
      combination with hyaluronan (HYAL EX-0001).
AB  - In a novel application, hyaluronan has been utilized as a delivery system for
      topical and i.v. therapeutics. Clinical trials and case reports show that topical
      diclofenac delivered in hyaluronan (HYAL CT-1101) is effective against basal-cell
      carcinoma and actinic keratosis. The effect of this drug formulation on tumour
      growth and angiogenesis, as well as granulomatous tissue angiogenesis, has been
      investigated experimentally. The evidence that hyaluronan has a permissive effect
      on the inhibition of granulomatous tissue angiogenesis by diclofenac (as assessed
      by the carminel/gelatin vascular casting method) when injected into the lesion or
      applied topically is reviewed. Topical diclofenac in hyaluronan also induces a
      regression of the existing neo-vasculature of granulomatous tissue when applied
      therapeutically. The diclofenac formulated in hyaluronan was also found to be
      profoundly effective against the development of subcutaneous Colon-26 tumours in
      syngeneic balb/c mice (T/C ratio after 12 days topical application of 0.174, p <
      0.0001). Analysis of the tumour vasculature showed that vascular development was
      retarded by 12 days. This was shown by the reduction in the tumour density of
      carmine in the vascular casts, as well as reduced blood-vessel density visualized
      by rat anti-mouse CD31 immunohistology. Hyaluronan alone had a significant effect
      on tumour development with a 50% inhibition of tumour growth and only a transient
      reduction in vascularity. The effects noted when diclofenac is formulated in
      hyaluronan, and applied topically, could be related to trans-dermal delivery and
      deposition properties of hyaluronan, and to the binding properties of hyaluronan
      to areas of pathology with high expression of hyaluronan receptors such as RHAMM,
      ICAM-1, and CD44.

PMID- 8867647
TI  - Histochemical studies of hyaluronan and the hyaluronan receptor ICAM-1 in
      psoriasis.
AB  - Histochemical stainings of frozen sections of human normal and psoriatic skin
      were used to study the localization of hyaluronan (HA) and intercellular adhesion
      molecule 1 (ICAM-1). HA staining was found in all areas of the skin, with the
      exception of the stratum corneum, in both normal and psoriatic cases without any
      apparent quantitative differences between the conditions. The staining for ICAM-1
      was detected in vessels in normal skin and at lower levels in normal areas of the
      skin in patients with psoriasis. However, in these patients the staining
      increased to about the same level as in normal skin after hyaluronidase treatment
      of the sections prior to staining. In psoriatic lesions, distinct staining for
      ICAM-1 was localized mainly to vessels and infiltrating leukocytes. Treatment of
      the sections with hyaluronidase increased the staining of vessels only slightly,
      but more strongly around leukocytes. These findings show that ICAM-1 is
      predominantly free from bound HA on vessel endothelium in psoriasis lesions but
      not on vessels in normal areas of the skin, and suggests that systematically
      administered HA, previously shown to reduce chronic inflammation in animal
      models, might have a beneficial effect in psoriasis via blocking of endothelial
      ICAM-1 and thereby causing a reduced invasion of leukocytes into the skin.

PMID- 8867648
TI  - Antioxidant effect of a Ginkgo biloba extract (EGb 761) on the retina.
AB  - Several investigations have recently shown that the retina is very sensitive to
      oxygenated free radicals (O2-, OH.) at the origin of the membrane phospholipids
      peroxidation. Peroxy radical (ROO.) release is responsible for the induction of
      electrophysiological disturbances leading to retinopathy development. As Ginkgo
      biloba extract (EGb 761, IPSEN, France) was reported to scavenge primary (O2-,
      OH.) and secondary (ROO.) free radicals, we evaluated its antioxidant effect on
      retinas of albino rats submitted to different types of aggressors. On isolated
      rat retina, EGb 761 given orally significantly protected against lipoperoxidation
      induced by a mixture of ferrous sulfate and sodium ascorbate added to the
      perfusion solution. With EGb 761, the decrease of the b-wave ERG amplitude was
      less pronounced and the retina survival was increased. EGb 761 was also effective
      against ischaemia-reperfusion disorders due to occlusion of the central retinal
      artery or by intraocular hypertony. Like other antioxidants such as superoxide
      dismutase tested on these models, EGb 761 significantly attenuated, according to
      a dose-response effect, the free-radical injury. EGb 761 reduces the decrease of
      the b-wave amplitude, the oedema, necrosis and ion homeostasis disturbances.
      Xenobiotics are also responsible for the retinotoxicity partly due to free
      radicals and PAF release. We noted an EGb 761 dose-dependent protective effect
      against acute and chronic chloroquine toxicity to the retina. The deleterious
      effect of chloroquine was characterized by a delayed b-wave and an asymmetry of
      the signal with slow declining b-wave. After EGb 761 treatment, the ERG aspect
      was partially normal. In conclusion, EGb 761, by its general free-radical
      scavenger properties, is an antioxidant that inhibits or reduces the functional
      and morphological retina impairments observed after lipoperoxide release.

PMID- 8867649
TI  - Effects of metadoxine on cellular formation of fatty acid ethyl esters in ethanol
      treated rats.
AB  - Free fatty acids (FFA) and fatty acid ethyl esters (FAEE) were extracted from
      different organs of rats administered ethanol, which was found to have induced
      FAEE formation, which reached its highest levels in the heart, followed by
      kidney, brain and liver; the ethanol administration resulted also in a marked
      increase of total FFA content, particularly in brain, kidney, heart and liver.
      Pretreatment of animals with Metadoxine one hour before ethanol administration
      inhibited significantly both FAEE and FFA accumulation in all organs examined.
      These effects were concomitant with the decreased levels of ethanol in blood
      found in alcohol-intoxicated rats pretreated with Metadoxine. Our results point
      to the role of fatty acid ethyl esters as possible mediators in the production of
      alcohol-dependent syndromes, especially in organs lacking oxidative pathways.
      Administration of Metadoxine, through an increment in alcohol metabolism and
      turnover, greatly reduces this metabolic abnormality, warranting its potential
      usefulness as a pharmacological tool in alcoholism management.

PMID- 8867650
TI  - Effect of argatroban on the formation of artificial thrombus on dogs.
AB  - In the present study, we have investigated the effects of a synthetic
      antithrombin, Argatroban, and an antiplatelet agent. Ticlopidine hydrochloride,
      on the weight of artificial thrombus. These drugs at various concentrations were
      added to canine bloods, which were adjusted to 20%, 40% and 60% of haematocrit,
      and an artificial thrombus was formed using a modification of Chandler's method.
      Argatroban inhibited the formation of artificial thrombus, and this marked
      inhibition was observed especially in the experiment using blood with a high
      value of Ht. On the other hand, Ticlopidine hydrochloride did not inhibit the
      formation of artificial thrombus. From these results, it becomes clear that the
      mechanism of inhibitory action of Argatroban on artificial thrombus formation is
      based on the inhibition of thrombin activity and not on the inhibition of
      platelet aggregation. In addition, it is suggested that Argatroban inhibits the
      aggregation of red blood cells in the manner of direct or indirect action.

PMID- 8867651
TI  - Determination of endothelin binding sites in bovine atrium and ventricle
      membranes: a model for binding studies in human cardiac tissue.
AB  - The characterization of the binding sites of endothelin (ET) could constitute a
      useful tool to better understand its role in different pathophysiological
      conditions in human myocardial tissue. Crude membrane fractions were prepared
      from bovine atrium and ventricle for binding-assay assessment; membranes were
      also prepared from portions of atrium or ventricle < 100 mg each, a size
      comparable with human surgical fragments, and Scatchard analysis was performed
      from each single fragment. Portions of cardiac tissue were homogenized in 10
      volumes of Tris/HCl buffer, 50 mM, pH 7.4, containing protease inhibitors; the
      supernatant was centrifuged at 50,000 x g for 30 min and the pellet stored at -80
      degrees C. 125-I-ET-1 binding was performed by using 50 micrograms of protein and
      scalar concentrations of radioligand (8-200 pM), at 37 degrees C for 4 h and was
      stopped by filtration through a glass-fibre filter. The specific binding was
      saturable (at 200 pM of 125-I-ET-1 for 100 micrograms/ml of protein); the
      equilibrium was reached in 4 h at 37 degrees C at a radioligand concentration of
      150 pM; a similar pattern, but a lower binding was obtained at 4 degrees C and 25
      degrees C; the binding linearly increased with protein concentrations from 12.5
      to 150 micrograms, and saturated at higher concentration. Non-specific binding
      was determined in presence of 0.1 microM unlabelled ET-1 and was about 2% of the
      total radioactivity added, for 125-I-ET-1 ranging from 8 to 200 pM, at 100
      micrograms/ml of protein. By Scatchard analysis Kd proved to be 20.7 +/- 3.9 and
      19.9 +/- 0.6 pM, Bmax 42.4 +/- 12.7 and 59.3 +/- 13.0 fmol/mg of protein, for
      atrium and ventricle respectively. Differential inhibition of binding was
      observed for the three ET isoforms; IC50 were similar for atrium and ventricle
      and proved to be 50 nM for ET-1 and ET-2 and > 200 nM for ET-3. This latter
      finding and the Scatchard analysis suggest the presence of a single class of
      binding sites in bovine cardiac membranes. No significant differences in absolute
      values of Kd and Bmax were found when cardiac membranes were obtained by small
      tissue fragments.

PMID- 8867653
TI  - Ectrodactyly of lower limbs, congenital heart defect and characteristic facies in
      four unrelated Dutch patients: a new association.
AB  - We report four cases with the unusual combination of lower limb ectrodactyly,
      congenital heart defect and a characteristic (albeit non-specific) facies.
      Because of the striking similarities between these cases we propose that they
      constitute a new association.

PMID- 8867652
TI  - Biochemical and biomolecular aspects of oxidative stress due to acute and severe
      hypoxia in human muscle tissue.
AB  - Mitochondrial oxidative stress was investigated in severe and acute hypoxia and
      in reperfusion applied to human muscle tissues. The biochemical and biomolecular
      relationship between the response of the respiratory-chain enzymic complexes and
      the metabolism of specific hypoxia stress proteins (HSP) suggest an adaptive
      mechanism which antagonizes the oxidative damage due to acute and severe tissue
      hypoxia.

PMID- 8867654
TI  - A new familial short stature syndrome: Brussels type.
AB  - A new association of congenital familial short stature with facial dysmorphism
      and osteochondrodysplastic lesions is described in two siblings. Clinical
      abnormalities include severe prenatal and postnatal growth failure and facial
      dysmorphism. Radiographs show osteochondrodysplastic lesions with a narrow
      thorax, short ribs, epiphyseal maturation delay and slightly deformed metaphyses.
      Microscopic analysis of the skeleton shows pathological features.

PMID- 8867655
TI  - Two brothers with deafness, femoral epiphyseal dysplasia, short stature and
      developmental delay.
AB  - Two brothers whose parents are second cousins have short stature, femoral
      epiphyseal dysplasia, umbilical and inguinal herniae, sensorineural deafness and
      developmental delay. Both are facially dysmorphic in that the face is triangular
      in shape with a pointed chin when viewed from the front.

PMID- 8867656
TI  - A neuropsychiatric disorder associated with dense calcification of the external
      ears and distal muscle wasting: 'Primrose syndrome'.
AB  - We report a 43-year-old man with a slowly progressive neurological disorder
      associated with impaired intellect, general stiffening of the spine and joints,
      craniofacial dysmorphism, hearing loss, and massive calcification of the external
      ears. Extensive laboratory investigations were nondiagnostic. This patient
      appears to have the same disorder reported previously in two individual case
      reports, supporting the idea that this phenotype may represent a recognizable new
      clinical entity. A review of literature pertaining to calcification of the
      external ears is presented.

PMID- 8867657
TI  - Filippi syndrome with mild learning difficulties.
AB  - A family is reported with two affected male siblings with features compatible
      with Filippi syndrome. These siblings are distinctive in having minimal
      developmental problems compared to the previously reported cases.

PMID- 8867658
TI  - New autosomal recessive syndrome of mental retardation, coarse face,
      microcephaly, epilepsy and skeletal abnormalities.
AB  - We describe two sibs, one male and one female, presenting a new autosomal
      recessive multiple congenital anomalies/mental retardation syndrome of 'coarse
      face', microcephaly, moderate to severe mental retardation, epilepsy and skeletal
      abnormalities.

PMID- 8867659
TI  - The microcephaly-lymphoedema syndrome: report of an additional family.
AB  - Fourteen patients from six families have been reported in which microcephaly
      occurs in conjunction with lymphoedema, with no evidence of mental retardation or
      serious neurological disabilities. Chorioretinal dysplasia was noted in a small
      number of affected individuals. Inheritance was either autosomal dominant or X
      linked and the question has been raised whether all these cases represent one
      entity or separate syndromes. We report the 7th family with two affected sibs of
      different sex. Developmental testing revealed normal to borderline intelligence
      associated with Attention Deficit Hyperactivity Disorder. The suggested mode of
      inheritance in this family is autosomal recessive. X-linked dominant inheritance
      cannot be ruled out, however, since the male was more severely involved than the
      female. We concur with previous authors that the association of microcephaly and
      lymphoedema is a distinct genetic syndrome and we propose to name this entity the
      'microcephaly-lymphoedema syndrome'.

PMID- 8867660
TI  - Fine-Lubinsky syndrome: a fourth patient with brachycephaly, deafness, cataract,
      microstomia and mental retardation.
AB  - In 1993, Suthers et al. reported on a child with an undiagnosed syndrome
      associating developmental delay, brachycephaly, deafness and cataracts. They
      discussed the possibility that this child had the same dysmorphic syndrome as the
      patient reported by Fine and Lubinsky in 1983. Twenty years ago, we examined a
      very similar patient who has been followed up to now. When she was a baby, she
      looked extremely similar to another patient, reported by Preus et al. in 1984. We
      now think that these four patients have in fact the same syndrome, the patient
      reported by Fine and Lubinsky being an example of a very severe expression of
      this condition, the other patients expressing different anomalies depending on
      the age at examination.

PMID- 8867661
TI  - Are cardio-facio-cutaneous syndrome and Noonan syndrome distinct? A case of CFC
      offspring of a mother with Noonan syndrome.
AB  - Cardio-facio-cutaneous syndrome is characterized by complex congenital heart
      disease, characteristic facies, ectodermal abnormalities, growth failure, and
      mental retardation. It has been described as a distinctive entity from Noonan
      syndrome. This paper presents a child with cardio-facio-cutaneous syndrome born
      to a mother with Noonan syndrome. This is suggestive of cardio-facio-cutaneous
      syndrome being a variable expression of Noonan syndrome.

PMID- 8867662
TI  - The cardio-facio-cutaneous (CFC) syndrome--two possible new cases and review of
      the literature.
AB  - We report two new patients, a boy and a girl, who show variable but specific
      manifestations of CFC syndrome. The patients differ in general appearance,
      severity of skin changes, cardiac involvement and in behaviour. The girl shows
      some additional clinical features such as easy bruising and altered sensation of
      the distal part of the limbs, which have never been observed in CFC syndrome, but
      have been described in a few patients with Noonan syndrome. We discuss our
      observations in relation to previous cases of CFC syndrome and the possible
      relationships between the Noonan and CFC syndromes. There is no doubt that the
      CFC and Noonan syndromes share many manifestations and it is extremely difficult
      if not impossible unequivocally to distinguish between these two syndromes.

PMID- 8867663
TI  - Meckel syndrome and Dandy Walker malformation.
AB  - We report on a child with typical features of Meckel syndrome in whom both
      encephalocele and Dandy Walker malformation (DWM) exist. Previous reports of DWM
      associated with cystic dysplasia of the kidney are reviewed.

PMID- 8867664
TI  - A second case of microcephaly, microphthalmia, ectrodactyly (split-foot) and
      prognathism (MMEP).
AB  - In 1993, Viljoen and Smart described a woman with ectrodactyly of the feet,
      midline facial cleft, microphthalmia, and mental retardation in association with
      a de novo chromosome 6;13 translocation. We present a man with similar features
      who had a normal karyotype.

PMID- 8867665
TI  - Anterior encephalocele and anophthalmia.
AB  - We report a patient of Baluchi origin with an anterior encephalocele,
      anophthalmia and dilated cerebral ventricles and discuss the possible etiology.

PMID- 8867666
TI  - Two more diagnostic signs in the Floating-Harbor syndrome.
AB  - A 6-year-old boy with the Floating-Harbor syndrome (F-HS) is described. We
      propose that his exceptionally high-pitched voice and supernumerary upper incisor
      are additional diagnostic signs of F-HS. The elevated gliadin antibody levels
      suggest coeliac disease, which has been described in three out of the 15
      previously reported F-HS patients. His facial features and delayed speech
      development are very characteristic but his shortness (-3 SD) is milder than
      usual. The patient is a sporadic case like all the F-HS cases so far.

PMID- 8867667
TI  - How do tumor necrosis factor receptors work?
AB  - Quite suddenly, a new level of understanding has been attached to the TNF ligand
      and receptor families. Many of the proximal transducers that signal the presence
      of TNF or its homologs have been identified, and certain components of the distal
      signaling pathway have emerged as well. We lack, however, a "movie" of the events
      that transpire when TNF binds its receptors on the surface of a cell. The facts
      in hand permit an educated approximation.

PMID- 8867668
TI  - Expression of an adenovirally encoded lymphotoxin-beta inhibitor prevents
      clearance of Listeria monocytogenes in mice.
AB  - The lymphotoxin (LT)-beta heterotrimer was recently identified as a molecule
      containing LT-alpha subunits, tethered to the cell through non-covalent
      association with an integral plasma membrane protein, derived from the LT-beta
      gene. Since knockout mutations of the LT-alpha gene yield animals that lack lymph
      nodes, whereas animals lacking either or both of the receptors for tumor necrosis
      factor (TNF) and LT-alpha homotrimers have normal lymph nodes, it has been
      inferred that the association between the LT-beta heterotrimer and its cognate
      receptor is required for lymph node ontogeny. Similarly, LT-beta and its receptor
      are thought to be important for development of the spleen. Since LT-alpha
      deficient mice lack lymph nodes, it is difficult to assess the extradevelopmental
      contribution of LT-beta to immune competence. To this end, we employed a strategy
      for the conditional blockade of LT-beta heteromer activity in normal mice. The
      interaction between LT-beta and its receptor is essential for the destruction of
      intracellular Listeria monocytogenes.

PMID- 8867669
TI  - Hemorrhage and resuscitation alter the expression of ICAM-1 and P-selectin in
      mice.
AB  - Acute inflammatory lung injury is a common clinical occurrence following blood
      loss and trauma, and is characterized by massive neutrophil infiltration into the
      lung. In order to better examine cell trafficking that may contribute to lung
      injury in this setting, we investigated in vivo mRNA levels and
      immunohistochemically determined expression of the adhesion molecules P-selectin
      and the intercellular adhesion molecule (ICAM)-1 in murine lungs over the 3-day
      period following hemorrhage and resuscitation. Significant increases in P
      selectin mRNA levels were present in lungs obtained 3 days after hemorrhage. ICAM
      1 mRNA levels were significantly increased 6 and 72 hr after hemorrhage.
      Immunohistochemical staining for P-selectin was enhanced on pulmonary vascular
      endothelium in all visible vessels at 6, 24, and 72 hr after hemorrhage. ICAM-1
      immunoreactivity was significantly increased on the alveolar epithelium at 6 and
      72 hr post-hemorrhage. These results suggest that increased expression of
      adhesion molecules in the lung at early post-hemorrhage timepoints may contribute
      to neutrophil infiltration into the lungs and the frequent development of acute
      lung injury following blood loss and trauma.

PMID- 8867670
TI  - Novel intracellular signaling function of prostaglandin H synthase-1 in NF-kappa
      B activation.
AB  - Many potent nonsteroidal antiinflammatory drugs (NSAIDs) exert their effects by
      inhibiting the cyclooxygenase activity of prostaglandin H synthase-1 (PGHS1, thus
      disrupting prostaglandin biosynthesis. However, these drugs do not block the
      activation of NF-kappa B, an inducible transcription factor which regulates
      numerous inflammation-related genes. Here we demonstrate that PGHS1 peroxidase, a
      NSAID-insensitive activity of PGHS1, mediates NF-kappa B activation through an
      intracellular reactive oxygen signaling pathway. Overexpression of PGHS1 strongly
      potentiated NF-kappa B activation by phorbol esters and dramatically elevated the
      generation of intracellular reactive oxygen species (ROS) in response to low
      concentrations of t-butyl peroxide. Both functions were dependent on PGHS1
      peroxidase activity and could be suppressed by the potent antioxidant pyrrolidine
      dithiocarbamate. In contrast, elimination of PGHS1 cyclooxygenase activity by
      NSAIDs or site-directed mutagenesis failed to block ROS production or NF-kappa B
      activation. Thus, PGHS1 peroxidase serves an intracellular signaling function
      leading to NF-kappa B activation, separable from its role in prostaglandin
      synthesis.

PMID- 8867671
TI  - Conserved high-affinity NF-kappa B binding site in the interferon regulatory
      factor-1 promoter is not occupied by NF-kappa B in vivo and is transcriptionally
      inactive.
AB  - The promoter of the interferon regulatory factor-1 (IRF-1) gene contains at
      position -47 to -38 an evolutionary conserved binding sequence for the inducible
      transcription factor NF-kappa B. This site is highly homologous to a
      transcriptionally active site from the MHC class I enhancer. In this study, we
      show by in vitro assays using purified NF-kappa B that the kappa B motif in the
      IRF-1 promoter binds the factor specifically and with high affinity, comparable
      to various other cis-acting kappa B elements. Two copies of the IRF-1 kappa B
      site fused to the heterologous c-fos promoter conferred induction of a
      chloramphenicol acetyl transferase (CAT) reported gene in response to stimulation
      of L929 fibroblasts with various NF-kappa B inducers, such as tumor necrosis
      factor alpha (TNF alpha) or phorbol 12-myristate 13-acetate (PMA). Mutation of
      the binding site completely abolished transcriptional inducibility of the
      heterologous promoter. Surprisingly, the same IRF-1 kappa B motif in context of
      the homologous IRF-1 promoter was transcriptionally inactive in CAT assays. The
      very weak induction of the IRF-1 promoter in response to TNF treatment or
      infection of fibroblasts with Newcastle disease virus (NDV) was barely affected
      by point mutation of the kappa B site or loss of the site by truncation of the
      promoter. Analysis of the occupational state of the chromosomal IRF-1 kappa B
      site by in vivo foot-printing revealed that no footprint was induced over the
      kappa B motif in the IRF-1 promoter after PMA treatment of L929 fibroblast cells,
      despite the simultaneous induction of IRF-1 mRNA and NF-kappa B binding activity.
      Constitutive footprints were detected at a CCAAT and GC-rich region in the
      promoter. This is the first example of a high-affinity NF-kappa B binding site
      within a promoter which may not participate in transcriptional regulation under
      conditions activating NF-kappa B DNA binding and gene expression.

PMID- 8867672
TI  - NF-kappa B is activated during acute inflammation in vivo in association with
      elevated endothelial cell adhesion molecule gene expression and leukocyte
      recruitment.
AB  - Leukocytes accumulate at sites of inflammation in response to the induced
      expression of endothelial cell adhesion molecules. The nuclear transcription
      factor kappa B (NF-kappa B) plays a critical role in the cytokine-induced
      expression of these genes in cultured endothelium. We examined the relationship
      between NF-kappa B activation and endothelial cell adhesion molecule gene
      expression in vivo during the initiation of acute inflammation. Nuclear NF-kappa
      B DNA-binding activity was rapidly increased within lung and heart tissues of
      rats administered endotoxin, consistent with the translocation of NF-kappa B
      complexes from the cytoplasm to the nucleus. This NF-kappa B was composed of p50
      and p65 subunits, and could bind NF-kappa B elements in the E-selectin promoter.
      NF-kappa B activation was maximal within 30 min and persisted for at least 3 hr
      after endotoxin treatment. NF-kappa B activation preceded the transcriptional
      activation of the P-selectin, E-selectin, VCAM-1, and ICAM-1 genes. In the lung,
      increased expression of P-selectin and ICAM-1 protein was detected
      immunohistochemically. These molecular events were temporally associated with the
      sequestration of leukocytes and the development of pulmonary inflammation. NF
      kappa B activation is therefore an early event in the initiation of acute
      inflammation in vivo. This molecular pathway may be of consequence in the
      pathogenesis of acute inflammatory disease.

PMID- 8867673
TI  - Activation of p58c-fgr and p53/56lyn in adherent human neutrophils: evidence for
      a role of divalent cations in regulating neutrophil adhesion and protein tyrosine
      kinase activities.
AB  - Tumor necrosis factor (TNF) stimulates generation of reactive oxygen
      intermediates, secretion of granule constituents, and rearrangement of the
      cytoskeleton in neutrophils (PMN); this response requires that PMN be adherent to
      plasma or extracellular matrix proteins, and is dependent on beta 2 integrins.
      Tyrosine phosphorylation of distinct proteins [Fuortes et al., J Cell Biol
      120:777-784, 1993] and activation of the protein tyrosine kinase p58c-fgr [Berton
      et al., J Cell Biol 126:1111-1121, 1994] were recently recognized as signals
      involved in beta 2 integrin-dependent responses of TNF-treated PMN. As the
      integrin capability to bind their ligands is regulated by divalent cations we
      investigated whether modulation of PMN adhesion to fibrinogen by divalent cations
      also affected activation of protein tyrosine kinases. In the absence of divalent
      cations or in the presence of Ca2+ alone, PMN did not adhere to fibrinogen in
      response to TNF. However, Mg2+, either alone or together with Ca2+, promoted
      stimulated adhesion to fibrinogen. We also found that Mn2+ promoted PMN adhesion
      to fibrinogen without additional stimuli. Analysis of the activity of two src
      family tyrosine kinases, p58c-fgr and p53/56lyn, showed that their
      autophosphorylating kinase activity strictly correlated with adhesion. In fact,
      only in the presence of Mg2+, but not in the absence of divalent cations or in
      the presence of Ca2+ alone, TNF increased p58c-fgr and p53/56lyn kinase
      activities; and this was prevented by anti-CD18 antibodies. In addition, Mn2+
      strongly promoted activation of p58c-fgr and p53/56lyn without additional
      stimuli. Analysis of tyrosine phosphorylated proteins with anti-phosphotyrosine
      immunoblots showed that divalent cations regulated adhesion and protein tyrosine
      phosphorylation in the same fashion. Detergent extraction of proteins showed that
      the Mg(2+)-dependent, TNF-stimulated adhesion redistributed p58c-fgr and
      p53/56lyn to a Triton-insoluble fraction. In addition, analysis of p58c-fgr
      activity allowed us to demonstrate that the fraction of p58c-fgr which became
      Triton-insoluble displayed a higher kinase activity. These findings establish
      that PMN adhesion signals for activation of two different src family tyrosine
      kinases. The evidence that Mn2+, a strong promoter of integrin function, induces
      adhesion and activation of tyrosine kinases without additional stimuli suggest
      the existence of a direct link between beta 2 integrins binding to fibrinogen and
      activation of tyrosine kinases in neutrophils.

PMID- 8867674
TI  - Induction of cell death by myristylated death domain of p55 TNF receptor is not
      abolished by Iprcg-like point mutation in death domain.
AB  - We transiently expressed the intracellular domains of p55 TNF receptor (TNFR1) as
      either a cytosolic- or a membrane-associated form and examined their effects on
      the endogenous receptor-mediated gene expression as well as on cell viability. We
      found that gene expression as measured by luciferase activity under NF-kappa B
      controlling elements was blocked by all forms of the intracellular domain of
      TNFR1. The blockade of reporter gene expression was due to the cell death induced
      by the intracellular domain of TNFR1 per se. The killing mechanism of the
      intracellular domain peptides appeared to be apoptotic. Interestingly,
      myristylated form of the intracellular domain, consisting of mainly death domain
      showed the most potent cell-killing activity. Moreover, this myristylated death
      domain could still induce cell death even if lprcg-like point mutation (Leu351 to
      Ala), which has been reported to abrogate TNF-induced cytotoxicity, was
      introduced. This result suggests that the myristylated death domain activates an
      additional death signaling pathway which is not involved in TNF-induced cell
      death.

PMID- 8867675
TI  - Effect of fluorescein on the tear stability of Hong Kong-Chinese.
AB  - We used the noninvasive tear break-up time (NITBUT) technique to measure the tear
      stability of 24 asymptomatic Hong Kong (HK)-Chinese before and after instillation
      of fluorescein. One eye was used as the test eye while the fellow eye served as
      control. We compared the NITBUT of the test eyes pre- and postinstillation of
      fluorescein, and compared the NITBUT of the test eyes measured postinstillation
      of fluorescein with the NITBUT of the control eyes. After instillation of
      fluorescein, both longer and shorter NITBUT were recorded in the test eyes;
      similar results were observed for the control eyes (no fluorescein instilled)
      between the first and second measurement. The median NITBUT of the test eye pre-
      and postfluorescein instillation were 13.3 and 13.0 s, respectively. Fluorescein
      did not cause any significant change in the NITBUT of HK-Chinese and the
      instillation of fluorescein in one eye does not affect the NITBUT of the fellow
      eye. Fluorescein did not appear to affect the locations of tear break up (tear
      defects) observed using the NITBUT test. Tear defects are most frequent near the
      inferior periphery of the cornea.

PMID- 8867676
TI  - Effects of coatings on the fracture resistance of ophthalmic lenses.
AB  - BACKGROUND: Scratch-resistant (SR) and anti-reflective (AR) coatings are commonly
      applied to plastic ophthalmic lenses. Fracture resistance is greatly affected by
      surface characteristics, and coatings may have a weakening effect. Static load
      testing is an efficient, quantifiable alternative to the drop ball test and has
      been suggested as useful for comparing lenses of a given material. METHODS: An
      Instron static load tester was used to test the fracture resistance of 140 CR-39
      lenses divided into 4 groups: uncoated, prepared for AR coating but not actually
      coated, AR coated, and factory SR coated. RESULTS: Compared to the control
      uncoated group, AR coating reduced the required fracture energy by 63% and SR
      coating by 57%. Preparation for AR coating had no significant effect.
      CONCLUSIONS: These results are at least qualitatively consistent with drop ball
      testing and have significant implications as new plastic materials are developed,
      made thinner, and variously coated.

PMID- 8867677
TI  - Spoilation and clinical performance of monthly vs. three monthly Group II
      disposable contact lenses.
AB  - Twelve subjects were fitted with a high water content, nonionic contact lens
      (Pilkington Barnes-Hind "Precision UV"), which was either replaced every month
      for 3 months or worn for 3 consecutive months before replacement occurred. Visual
      quality, high and low contrast acuity, and comfort were unaltered with either
      replacement schedule, but overall satisfaction was significantly greater with the
      shorter replacement schedule (p = 0.04). Front surface wettability revealed a
      large amount of intersubject variability and was reduced at the 3-month visit
      with the longer replacement period lenses (p = 0.003). Visible deposits also
      increased with longer replacement times (p < 0.05). Laboratory-based analytical
      results showed that both gross lipid and gross extractable protein significantly
      increased in the 3-month lenses compared with the 1-month lenses, with 44% less
      lipid accumulation and 60% less protein deposition occurring with the shorter
      replacement time. The results support the replacement of high water content
      lenses on a monthly basis.

PMID- 8867678
TI  - Clinical evaluation of back optic radius and power determination by age in
      pediatric aphakia due to congenital cataract fitted with a Silicone Elaster
      contact lens.
AB  - The purpose of this study was to provide optometrists with suggested base curves
      and powers for initial lens choice based on the infant's age. A retrospective
      chart review of 16 congenital cataract patients fitted at U.C. Davis Eye Clinic
      between July 1987 and May 1993 was performed. Patients with associated ocular
      pathologies were excluded. All patients were fitted with a Bausch & Lomb Silsoft
      lens, a Silicone Elastomer, set at a 3.00 D myopic posture, which was decreased
      with the child's increasing age and activity. This study provides a graphical
      approach to pediatric aphakic silicone elastomer contact lens fitting. Best-fit
      regression lines for both graphs have an r squared value better than 0.9.
      Optometrists will now be able to reference the Base Curve vs. Age and Power vs.
      Age graphs to determine the initial lens choice when keratometry is unachievable.
      Furthermore, the data suggest a need for an increased range of powers provided by
      the Silicone elastomer lens in order to approximate normal visual development.

PMID- 8867679
TI  - Lens adherence and postlens tear film changes in closed-eye wear of hydrogel
      lenses.
AB  - BACKGROUND: Lens adherence and a reduced postlens tear film circulation have been
      suggested as factors contributing to some adverse reactions in extended wear of
      hydrogel contact lenses. In this study, we determined lens fitting and postlens
      tear film characteristics during closed-eye wear. METHODS: Twenty subjects wore
      hydrogel lenses for 3 h of eye closure, followed by 30 min of open-eye wear. Lens
      movement was measured with a video biomicroscope. Postlens tear film appearances
      in specular reflection were classified as either amorphous, or as one of four
      color intensity grades, where a colored appearance was taken as indicative of a
      depleted postlens tear film. RESULTS: All subjects showed lens adherence
      (movement < 0.1 mm) and postlens tear film depletion within 45 min of eye
      closure. These changes were sustained for the remainder of the closed-eye period,
      but were reversed within 15 min of eye opening. Lens adherence was associated
      with colored postlens tear film patterns of any intensity. CONCLUSION: Closed-eye
      wear was invariably associated with the onset of lens adherence and postlens tear
      film depletion. This finding emphasizes the need for adequate lens movement
      during the open-eye phase of extended wear.

PMID- 8867680
TI  - Changes in myopia, visual acuity, and psychological distress after biofeedback
      visual training.
AB  - The effects of auditory biofeedback training on myopia, visual acuity (VA), and
      psychological distress were evaluated in a controlled prospective study involving
      55 mildly myopic (< or = -3.5 D) high school students. These myopes were divided
      into 2 groups, matched for age and dioptric defect: 33 were treated with visual
      training and 22 were not; 27 emmetropic subjects formed a further control group.
      Subjects were evaluated at the baseline (T0), at 10 weeks after the end of the
      treatment (T1), and after an interval of 12 months (T2) from the baseline for:
      (1) manifest and cycloplegic refraction, and the difference between them
      (cycloplegic tonus); (2) VA measured with a conventional optotype in all
      subjects, and also with a computer-generated optotype in the treated group; and
      (3) psychometric values and personality profile. At T2, myopia had significantly
      worsened both in the treated and in the control myopes; VA in the treated myopes
      appeared significantly improved when measured by the conventional optotype, but
      unchanged when measured by computer. Psychometric scores improved significantly
      in the treated myopes and in the emmetropic controls. Objectively the
      autorefractometer showed that 38% of the myopes had voluntary control of positive
      accommodation, i.e., the ability to increase spherical defect; no voluntary
      control of negative accommodation was observed. An increase in VA was associated
      with a significant increase in the foveation time (i.e., the period of time when
      the target is imaged on the fovea and the eye is motionless), and was partly
      attributable to a learning effect. In conclusion, biofeedback visual training had
      a positive effect on psychological distress and subjective VA improvement, but
      failed to reduce the existing myopia or delay its evolution.

PMID- 8867681
TI  - Stereoacuity development: 6 months to 5 years. A new tool for testing and
      screening.
AB  - A new tool to measure changes in random dot stereoacuity development from 6
      months to 5 years of age was developed and tested. Either a forced choice or
      operant preferential looking (PL) paradigm with a happy face target was
      successfully used to test 136 children. Results indicate that stereoacuity
      measurements continue to develop through the first years of life. Although
      children below 24 months of age can be expected to have stereo thresholds in the
      range of 300 sec arc, there is a transition at approximately 24 months of age
      after which stereoacuity approaches adult levels. The sensitivity of this test in
      detecting binocular vision problems was 80%. These results provide guidelines for
      the assessment of stereoacuity in young children and also provide a new tool for
      the early detection of binocular vision anomalies.

PMID- 8867682
TI  - The Freiburg Visual Acuity test--automatic measurement of visual acuity.
AB  - The Freiburg Visual Acuity test is an automated procedure for self-administered
      measurement of visual acuity. Landolt-Cs are presented on a monitor in one of
      eight orientations. The subject presses one of eight buttons, which are spatially
      arranged on a response box according to the eight possible positions of the
      Landolt-Cs' gap. To estimate the acuity threshold, a best PEST (best Parameter
      Estimation by Sequential Testing) procedure is used in which a psychometric
      function having a constant slope on a logarithmic acuity scale is assumed.
      Measurement terminates after a fixed number of trials. With computer monitors,
      pixel-discreteness artifacts limit the presentation of small stimuli. By using
      anti-aliasing, i.e., smoothing of contours by multiple gray levels, the spatial
      resolution was improved by a factor of four. Thus, even the shape of small
      Landolt-Cs with oblique gaps is adequate and visual acuities from 5/80 (0.06) up
      to 5/1.4 (3.6) can be tested at a distance of 5 m.

PMID- 8867683
TI  - Optic nerve head stereoscopic digital imaging using bichromatic techniques.
AB  - The variability of optic nerve parameters obtained with versions 3.4 and 3.5 of
      the Topcon IMAGEnet computer stereo analysis system was studied. The consistency
      of horizontal cup-to-disc ratio, vertical cup-to-disc ratio, cup volume,
      neuroretinal rim area, neuroretinal rim-to-disc area, and the percentage of
      poorly correlated conjugate points (bad points) on the stereo pair was compared.
      The updated computer program for stereo analysis provides a significantly more
      accurate means to assess both the cup volume and the neuroretinal rim area as
      evidenced by the smaller number of bad points.

PMID- 8867684
TI  - A new Arabic distance visual acuity chart.
AB  - BACKGROUND: A new Arabic visual acuity chart has been designed using the various
      recommendations made by vision scientists for achieving a standardized acuity
      chart. Our goal was to design a standardized Arabic distance visual acuity chart.
      METHOD: The chart is based on the design principle devised by Bailey and Lovie.
      Twelve Arabic letters of nearly equal legibility values, which could be
      constructed on a 5 by 5 Snellen framework, were used. The LogMAR method of
      scaling visual acuity was used, hence the size of letters in the rows progresses
      in a uniform step of 0.1 logarithm unit. RESULT: The size of letters in the chart
      ranged from 58.2 to 4.6 mm, corresponding to visual acuity of 4/40 to 4/3 (6/60
      to 6/4) (20/200 to 20/15). The chart is designed for use at 4 m; acuity values
      for a 6-m testing distance are, however, provided on the chart. CONCLUSION: The
      chart will be useful for examining Arabic speaking patients.

PMID- 8867685
TI  - Hyperacuity test to evaluate vision through dense cataracts; research preliminary
      to a clinical study. III. Data on normal subjects obtained with and without a
      pseudo-nuclear cataract 6/60 (20/200) at the Aravind Eye Hospital, Madurai,
      India.
AB  - Using a recently discussed three-point Vernier alignment test, data were obtained
      on normal subjects with and without a pseudo-nuclear cataract 6/60 (20/200) at
      the Aravind Eye Hospital, Madurai, India. This experiment is a critical control
      exercise. The pseudo-cataract caused measurably and predictably reduced Vernier
      alignment thresholds, there were no meaningful differences between eyes, and
      necessary modifications in protocol for a later clinical study were defined.

PMID- 8867686
TI  - Use of protective filters by fluorescein angiography nursing staff.

PMID- 8867687
TI  - Detachment of desmosomes in a microcystic meningioma.
AB  - This report demonstrates the detachment of desmosomes in the microcystic area of
      a frontal convexity meningioma removed from a 69-year-old woman. Well-developed
      interdigitations of the tumor cell processes with numerous desmosomes and with
      narrow extracellular spaces were characteristic features of the solid area of the
      meningioma. By contrast, the microcystic area of the tumor had markedly distended
      extracellular spaces. Various stages in the separation of desmosomal attachments
      were seen in this area. The observed configurations ranged from the widening of
      opposing junctions to the formation of large cavities where hemidesmosome-like
      structures were evident. The latter lacked basal lamina, and are considered to
      represent a transition leading to the loss of desmosome, and thus involved in the
      enlargement of the extracellular space in microcystic meningiomas.

PMID- 8867688
TI  - Development of medullomyoblastoma from classical medulloblastoma following a long
      term latency.
AB  - A case of medullomyoblastoma is described. Partial removal of a cerebellar tumor
      was performed at the age of 21 months old, and histopathological diagnosis was
      medulloblastoma. Death occurred at 15 years of age, due to pneumonia and relapse
      of the tumor. Autopsy revealed well-differentiated muscular and ependymal
      components disseminated in the medulloblastic area. Immunohistochemically, desmin
      was positively detected in not only autopsy materials but also undifferentiated
      cells of the surgical specimens, suggesting prospective myoblastic
      differentiation.

PMID- 8867689
TI  - Origin of ciliated craniopharyngioma: pathological relationship between Rathke
      cleft cyst and ciliated craniopharyngioma.
AB  - Histological study was undertaken on ciliated craniopharyngioma and Rathke cleft
      cyst, to know the origin of ciliated craniopharyngioma. Subjects were 7 cases
      with symptomatic Rathke cleft cysts and a ciliated craniopharyngioma. Light and
      electron microscopic observations were made on surgically resected specimens of
      the 8 cases. The ciliated craniopharyngioma was composed mainly of papillary type
      of craniopharyngioma and of dispersed ciliated columnar epithelium including
      goblet cells. Four cases with Rathke cleft cyst showed squamous metaplasia of
      which the basal cells were histologically similar to that of papillary type of
      craniopharyngioma. Other 3 cases of Rathke cleft cyst, basal cells were revealed
      to have tonofilaments and desmosomes. It seems possible that ciliated
      craniopharyngioma has derived from the basal cells of Rathke cleft epithelium.

PMID- 8867690
TI  - Radioimaging of human glioma by indium-111 labeled G-22 anti-glioma monoclonal
      antibody.
AB  - We previously have reported that indium-111 labeled anti-glioma monoclonal
      antibody G-22 (111In-G-22) exhibits diagnostic potential against human glioma
      xenografts in athymic mice. Herein, we report the selective tumor localization of
      111In-G-22 in patients with glioma. Five patients were administered an average of
      2.2 mCi of 111In-G-22 whole IgG intravenously. No immediate or delayed side
      effects were attributable to 111In-G-22 injection. Serial gamma scintigraphy and
      single photon emission computed tomography (SPECT) were performed, and the
      distribution in the brain and intratumoral accumulation of 111In-G-22 were
      evaluated. CT and/or magnetic resonance (MR) images were performed simultaneously
      and these images were compared. In the case of malignant glioma, tumor-imaging
      was successfully obtained beginning at 6 h following injection with a maximum
      uptake tumor/brain ratio at 48 h. The distribution of 111In was selective. It
      predominantly accumulated in the biologically active areas of the tumor.
      Furthermore, the tracer uptake appeared to correlate with the histologic tumor
      grade. This confirms the G-22 monoclonal antibody specifically binds to
      biologically active and malignant glioma tissue, and tumor-imaging using 111In-G
      22 may give support to the diagnosis of malignant glioma.

PMID- 8867691
TI  - Clear cell variants of intracranial tumors: meningioma and ependymoma.
AB  - We report two cases of rare histological types of intracranial clear cell tumor.
      Case 1: The tumor, on the left frontal convexity in a 64-year-old woman,
      consisted largely of polygonal cells with clear cytoplasm which were divided into
      lobules of uneven size by abundant fibrous connective tissue. Most of the tumor
      cells were immunopositive for epithelial membrane antigen and vimentin.
      Ultrastructurally, the tumor cells showed conspicuous interdigitations of their
      plasma membranes with frequent junctional complexes, and contained numerous
      glycogen granules in the cytoplasm and its processes. Occasionally, amianthoid
      collagen fibers were found in the fibrous stroma. Our diagnosis of this tumor was
      clear cell meningioma. Case 2: The tumor, in the right cerebellar hemisphere in a
      64-year-old woman, consisted of round, clear cells with a honeycomb-like pattern.
      The tumor cells were positive for glial fibrillary acidic protein, vimentin and S
      100 protein. Ultrastructurally, the tumor was composed of round cells arranged in
      a cell-to-cell pattern, and the adjacent cells often formed microrosettes
      containing microvilli in their lumina. There were scattered cells with
      accumulatios of glycogen granules in their cytoplasm. Our diagnosis of this tumor
      was clear cell ependymoma. From the light microscopic features of these tumors,
      it does not necessarily seem easy to discriminate them from other intracranial
      tumors composed of similar clear cells, such as oligodendroglioma, central
      neurocytoma, hemangioblastoma and metastic renal cell carcinoma. Ultrastructural
      examination is crucial in the identification of the clear cell variants of
      meningioma and ependymoma.

PMID- 8867692
TI  - Immunohistochemical and electron microscopic study of subependymal giant cell
      astrocytoma.
AB  - Six cases of subependymal giant cell astrocytoma (SGCA), five associated with
      tuberous sclerosis (TS), were reviewed by light microscopy, electron microscopy
      and immunohistochemistry. Histologically, all cases showed features typical of
      SGCA. GFAP and neurofilament expression were found in all cases. Synaptophysin
      and myelin basic protein were positive in single different cases. The MIB-1
      positive rate was 0% in 4 cases, 3% in a case with recurrence after a partial
      resection, and 6.4% in another case with a rapid growing tumor. By electron
      microscope, glial filament was identified in the tumor cells of all cases,
      whereas none of them showed any ultrastructural evidence of a neuronal origin. We
      therefore suggest that SGCA is a glial origin tumor, arising from the astrocytic
      part of a subependymal nodule--the most common cerebral lesion of tuberous
      sclerosis caused by distorted migration of the germinal mantle-the neuronal part
      of which remains as entrapped remnants of dysgenetic, incompletely expressed
      neuronal cells.

PMID- 8867693
TI  - Brain tumor: immunohistochemical studies on the stress-response proteins, p53
      protein and proliferating cell nuclear antigen.
AB  - This retrospective immunohistochemical study compares the expression of five
      stress-response (heat-shock) proteins (srp's) [srp 90, srp 72, srp 27, alpha B
      crystallin and ubiquitin], p53 protein and proliferating cell nuclear antigen
      (PCNA) in 118 primary brain tumors and 21 carcinoma metastases to the central
      nervous system. Serial sections of formalin-fixed, paraffin-embedded tissues were
      used. Most astrocytomas (9/13), ependymomas (5/5), glioblastoma multiforme (GBM)
      (11/12), schwannomas (19/21), meningiomas (22/23) and breast carcinoma metastases
      (Br-Mt) (9/10), and some medulloblastomas (5/15), primitive neuroectodermal
      tumors (PNETs) (5/11), pituitary adenomas (4/7) and lung carcinoma metastases
      (6/11), but none of 10 oligodendrogliomas had tumor cells that expressed one or
      more (up to five) srp's. The percentage of tumors with p53-positive cells was
      variable; the proportion was highest among srp-expressing GBMs (mean: 16.1%) and
      Br-Mts (mean: 15.3%). The mean PCNA-labeling index (LI) also varied, ranging from
      1.2% in the group of pituitary adenomas to 24.5% in Br-Mts, with GBMs (20.4%) and
      medulloblastomas (18.4%) approaching the latter value. PCNA-LI was higher in the
      astrocytomas, GBMs, medulloblastomas and PNETs that expressed srp's than in those
      did not. A high proportion of p53-positive cells (31.3 to 59.0%) and the highest
      PCNA-LIs (41.0 to 49.0%) were seen in two GBMs and one Br-Mt that expressed all
      five srp's. We conclude that primary and metastatic tumors of the brain produce
      one or more stress-related proteins, and that a variable proportion of the tumor
      cells have immunohistochemically-detectable p53, the expression of which may
      depend, at least in part, on the growth potential of a given tumor.

PMID- 8867694
TI  - Proliferating cell nuclear antigen (PCNA) and nucleolar organizer regions (NORs)
      in benign, atypical and malignant meningiomas.
AB  - Expression of proliferating cell nuclear antigen (PCNA) and numbers of nucleolar
      organizer regions (NORs) were studied by immunohistochemistry and the silver
      staining technique in 99 meningiomas and related to histopathologic grading,
      recurrence and their predictive value for recurrence. The results indicated that
      there was a significant correlation between PCNA or AgNORs and histopathologic
      grading of meningiomas. Slightly higher expression of PCNA in atypical
      meningiomas was correlated with the increased recurrence rate; however,
      expression of PCNA and numbers of AgNORs in meningiomas are not reliable criteria
      to predict tumor recurrence.

PMID- 8867696
TI  - Melanotic papilloma of the choroid plexus: report of a case with implications for
      pathogenesis.
AB  - A case of pigmented choroid plexus papilloma removed from the 4th ventricle of a
      43-year-old man is reported. The tumor showed histologic, immunophenotypic, and
      ultrastructural features of neoplastic choroid plexus epithelium. There was no
      evidence of melanosomal activity or neurosecretion. The pigment consisted of an
      intimate association of lipofuscin and neuromelanin, indicating autocatalytic
      peroxydation of the former as a putative way of melaninogenesis. The low
      proliferation rate of the tumor together with immunohistochemical evidence of
      inactivation of p53 protein suggest a delayed turnover of neoplastic cells as a
      possible source of lipofuscin accumulation.

PMID- 8867695
TI  - Proliferative potential and malignant transformation of ganglioglioma:
      immunohistochemical studies by MIB-1 and p53 staining.
AB  - We studied two cases of ganglioglioma immunohistochemically by MIB-1 and p53
      staining. The positive rate of MIB-1 in the ganglionic cells was 5.5% in Case 1
      and 7.8% in Case 2, and that of MIB-1 in the gliomatous cells was 1.4 and 6.6%
      respectively. The labeling index of p53 in the ganglionic cells was 7.3% in Case
      1 and 7.7% in Case 2, and that of the gliomatous cells was 1.9 and 3.4%
      respectively. MIB-1 and p53 did not stain ganglionic precursor cells. These
      results indicate that the ganglionic cells also take part in proliferation and
      have potential of malignant transformation.

PMID- 8867697
TI  - Sialic acid--marker of development and differentiation.
AB  - The authors discuss the role of structural diversity of various sialic acids in
      glycoconjugates, i. e. in glycoproteins and glycolipids of cell membranes and of
      body fluids under various physiologic and pathologic conditions, as summarized in
      recent reviews. Furthermore they report the conclusions of their own experiments
      regarding desialylation of intestinal brush-border enzymes during postnatal
      development in the rat and its induction after hydrocortisone injection. The
      mechanism of desialylation was investigated in the differentiating cells of
      Lieberkuhn crypts and at the levels of sialyltransferase transcription and of
      glucocorticoid receptors. These results are correlated with the findings of other
      authors and compared with the effect of dexamethasone in organ cultures of the
      fetal rat intestine.

PMID- 8867698
TI  - Prenatal biochemical diagnostics of inborn developmental defects.
AB  - Screening of pathological pregnancies with the use of biochemical markers
      determined in maternal serum is now widely accepted as a useful procedure. In our
      experience, the main contribution is a finding of abnormal values of one or more
      of the markers, which will advise gynecologist upon a possibility of a risk
      pregnancy.

PMID- 8867700
TI  - Xanthine oxidoreductase. Biochemical, biological and pathogenic functions.
AB  - Primary biochemical role of xanthine oxidoreductase (XOR, EC 1.1.1.204 and EC
      1.1.3.22.) is the hydroxylation of hypoxathine and xanthine to form uric acid.
      This enzyme may produce very reactive oxygen forms which can be pathogenic.
      Although it is one of the longest known and most continuously studied enzymes,
      its biological function remains unclear. The review of these aspects is discussed
      in relation to the authors' experimental results.

PMID- 8867699
TI  - Dipeptidyl peptidase IV in cell proliferation and differentiation.
AB  - In this short review we discuss the present knowledge of a dipeptidyl peptidase
      IV (DPP-IV, EC 3.4.14.5) physiological role, paying special attention to its
      involvement in complex processes of the cell cycle. Our own results and recent
      experimental project are overviewed in this respect too.

PMID- 8867701
TI  - Melanogenuria: the past--the present--the future.
AB  - A short review on the development of the study of melanogenuria in malignant
      melanoma is presented.

PMID- 8867702
TI  - Zinc in pigmented cells and structures, interactions and possible roles.
AB  - Zinc is a feature trace element of pigment cells and tissues. Organelles, in
      which melanin is synthesized and stored, i.e. melanosomes, represent a zinc
      reservoir at the subcellular level. In order to understand function of metals in
      tissues, cells and their constituents, knowledge is needed on metal interactions
      with intracellular targets. The possible zinc ligands in pigment cells include
      melanin, metallothionein, melanotransferrin, B700 and related proteins, ferritin,
      zinc enzymes and low molecular weight ligands. Areas of a special interest in
      relation of pigment cells and structures to zinc--such as zinc effect on
      melanogenesis, zinc excretion and buffering by melanosomes, zinc function in free
      radical processes as well as zinc role in melanomas--have been reviewed. High
      level of zinc in pigment cells may indicate a physiological defense against the
      potential danger of oxidative stress.

PMID- 8867703
TI  - Molecular aspects of malignant melanoma. Role of protooncogenes and
      oncosuppressor genes.
AB  - This review summarizes current knowledge of oncogenes and tumour-suppressor genes
      in development and progression of malignant melanoma.

PMID- 8867704
TI  - Markers of melanogenesis in malignant melanoma.
AB  - Biochemical specifity of malignant melanoma is represented in part by the
      formation of specific cytoplasmatic particles of the pigment cell--melanosomes-
      in which the synthesis of pigment eumelanin and pheomelanin takes place and in
      part by the presence of a specific enzyme--tyrosinase--which catalyzes the
      formation of pigment eumelanin and pheomelanin and even the formation of specific
      metabolites (so called melanogens) which are excreted in increased amounts in the
      course of the disease. Tyrosinase and melanogens are specific for pigment cell
      and therefore can be used for monitoring of melanogenesis in malignant melanoma.
      When comparing our results and the results of other authors we can conclude that
      following of specific markers of melanogenesis in malignant melanoma should serve
      for the evaluation of prognosis of the disease. The study of melanoma markers is
      by far not finished. We do hope that nearly future will be able to give a
      sufficient answer to the question, whether melanogenuria is actually an
      expression of expected different biochemical or metabolic types of malignant
      melanoma on the one hand and/or biochemically or immunologically conditioned
      responses of the host organism on the other.

PMID- 8867705
TI  - Application of HPLC with photodiode array detection for systematic toxicological
      analyses of drug groups.
AB  - During four years experience high performance liquid chromatography (HPLC) with
      photodiode array detection has been proved to be the demanded method of
      systematic toxicological analysis (STA) for unknown drugs in biological sample
      because of separation efficiency, sensitivity, flexibility and identification
      potential. HPLC can be an easy way of quantitation as well. Ultraviolet spectra
      acquired with Waters 990+ photodiode array detector together with retention data
      are used to identify unknown or suspected drugs and metabolites in various
      biological material often after basic TLC examination of urine. At present
      spectrum library used for comparison involves 180 spectra of standards in acid
      and neutral media. Various sample preparation procedures have been tested and
      till now eight isocratic liquid chromatographic systems have been used routinely
      for sensitive screening in small samples, identification and/or quantitative
      assays of drug groups. These analytical systems are suitable for toxicological
      examinations of forensic cases, acute poisonings, drug abuse. They are convenient
      to subsequent monitoring of serum drug levels during treatment of an intoxication
      as well.

PMID- 8867706
TI  - Hormesis in effect of low uranium doses on organisms.
AB  - Uranium nitrate applied daily in small amounts per os (0.5-17 mg/l in drinking
      water) or per cuttim (0.2-0.8 g/kg) exerts positive effect on metabolism of
      phosphate ions by red blood cells in vitro. This positive effect changes to the
      negative one with increasing dose or exposure time. It may be assumed that most
      other cells in the organism are affected in the same way as erythrocytes and that
      similar effect might be observed with other harmful agents or substances.

PMID- 8867707
TI  - Systematic analytic procedure for identification of unknown medicaments in
      biological material.
AB  - The presented method has been used in toxicological practice for identification
      of unknown medicaments in biological material longer than fifteen years with good
      results. This method described as TLC/CR-screening is a combination of thin layer
      chromatography (TLC) with a system of colour reactions (CR-screening), the
      principle being evaluation of characteristic features (qualities) of each
      detected unknown substance (parent medicament form or its metabolite) from three
      points of view: the type of ionization during the extraction, the mobility in
      basic TLC-system in comparison with five reference standards, the reactivity with
      system reagents for detection. The properties of each detected substance
      expressed by adequate symbols are put together into three component codes, under
      which corresponding standards of medicaments and/or their metabolites can be
      found in the library of code system.

PMID- 8867708
TI  - Can chemiluminescent immunoanalysis of thyroid hormones stand for a reference
      method?
AB  - Some analytical properties of chemiluminescent immunoassays (ChLIA) for the
      estimation of total triiodothyronine (T3), total thyroxine (T4) and thyrotropine
      (TSH) in serum were studied and compared with radioimmunoanalysis (RIA) as a
      reference method. Measurement range of ChLIA for T3 is lower, for T4 is
      equivalent and for TSH is greater than by RIA methods. Analytical sensitivity of
      ChLIA is better for all three analytes. Also precision of ChLIA is much better.
      ChLIA method seems to be more resistant to lipaemia. When compared to secondary
      reference materials, i.e. to commercial control sera, higher accuracy can be
      evaluated. However, adjustment of the control sera and analytical methods to
      different primary standards and calibrators, resulting in disagreement of results
      with asigned values, seems to be evident. With respect to the accuracy of ChLIA
      further study should be performed involving primary standards. Other
      interferences except of lipaemia, which we refer to in our work, and problems of
      specificity also need to be elucidated.

PMID- 8867709
TI  - Control serum for therapeutic drug monitoring.
AB  - New control material EXAPHARM (IMUNA s.p., Sarisske Michalany, Slovakia) for
      therapeutic drug monitoring (TDM) was evaluated. It is produced in two types:
      Exapharm AED containing 6 antiepileptic drugs and Exapharm CARD with 4 cardiac
      and antiasthmatic drugs. Both contain horse serum as a matrix, which is different
      in some parameters from human serum. Our results approved an outstanding
      stability and inter-bottle homogeneity of the material. Evidence was presented
      that no interferences occur in high performance liquid chromatography (HPLC)
      under the conditions described. It is concluded, that this control serum is very
      suitable for TDM by HPLC.

PMID- 8867710
TI  - The importance of uric acid examination.
AB  - Uric acid is the end product of purine metabolism in man. The findings of human
      pathological levels of uric acid in serum and urine have in most patients serious
      clinical implications. This paper summarizes aspects of uric acid examination in
      clinical biochemistry laboratory. The clinical consequences of pathological
      levels of uric acid are shown. Uric acid is a useful diagnostic tool as screening
      for most of purine metabolic disorders. The importance of uric acid measurement
      in plasma and urine with respect of metabolic disorders is highlighted. Not only
      gout and renal stones are indications to send blood to the laboratory for uric
      acid examination. Also familial nephritis, neurological abnormalities with mental
      retardation are reasons to know uric acid levels in blood and urine. The results
      underline the importance of urinary uric acid investigation, which is often quite
      overlooked, and is helpful in differential diagnosis of gout. This work is
      dedicated to Professor Jan Horbaczewsky and his 110th anniversary of the opening
      of lessons in medical chemistry at the Czech medical faculty of Charles
      University in Prague.

PMID- 8867711
TI  - The first European pre-hospital active compression-decompression (ACD)
      cardiopulmonary resuscitation workshop: a report and a review of ACD-CPR.
AB  - Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) has been
      evaluated in animal cardiac arrest models and in human outcome studies. Blood
      flow to the brain and heart is significantly increased during ACD-CPR compared to
      standard CPR. Transoesophageal Doppler analysis indicates that ACD-CPR increases
      left ventricular blood volume, velocity of blood flow through the mitral valve
      (82-140%), and stroke volume (85%). Pressures, such as coronary perfusion-,
      systolic-, mean-, and diastolic aortic pressures, ETCO2, and tidal volume
      generated by chest compression and decompression, increase during ACD-CPR
      compared to standard CPR. Prehospital outcome studies have shown both positive
      and no extra benefit of ACD-CPR on return of spontaneous circulation, hospital
      admission, and discharge rates. The ACD-CPR method should be evaluated in
      patients with witnessed arrest receiving bystander CPR who are found in
      ventricular fibrillation and do not respond to the three initial DC shocks. There
      is no evidence that ACD-CPR is worse than standard CPR. Appropriate ACD-CPR
      training using a standardized curriculum must preceed its implementation. Long
      term neurologic outcome studies are needed.

PMID- 8867712
TI  - Towards early defibrillation--a nurse training programme in the use of automated
      external defibrillators.
AB  - It is essential that all health care professionals are regularly trained in the
      practice of basic life support (BLS). In most cases of cardiac arrest, the
      chances of a favourable outcome depend not only on efficient BLS, but also on the
      early use of defibrillation. In a hospital environment, the first responders are
      most likely to be members of the nursing staff. The potential advantage of these
      personnel being able to perform early defibrillation, as well as BLS, is
      considerable. We describe an initiative in which instruction in the use of
      automated external defibrillators (AEDs) was introduced into routine BLS training
      sessions, with the aim of developing this capability. Using specifically-acquired
      training aids, 43 nurses and nine other members of the non-medical staff were
      trained in 12 teaching sessions over a period of 4 months. Refresher training was
      carried out after 6 months and 37 nurses were retrained during six sessions using
      a similar syllabus. The programme was well-received by all students, and a higher
      than expected level of motivation and competence was achieved. Throughout
      retraining all nurses appreciated the key importance of early defibrillation. We
      conclude that, although the initial workload is high, it is entirely feasible to
      augment BLS training for health care professionals with instruction in the use of
      AEDs. We recommend that this potentially life-saving tuition programme be widely
      adopted.

PMID- 8867713
TI  - The relationship between rate of chest compression and compression:relaxation
      ratio.
AB  - One of the arguments put forward in support of a relatively fast rate of chest
      compression during CPR, is that it facilitates the achievement of a high
      compression:relaxation ratio. This has been shown to increase blood flow. In this
      study a group of volunteers carried out chest compression at the rate that each
      felt was correct and comfortable. There was no significant relationship between
      compression rate and compression:relaxation ratio. In a second study volunteers
      carried out chest compression on a manikin at rates of 40/min; 60/min; 80/min and
      100/min. There was no significant rate related difference in the
      compression:relaxation ratios recorded. The ability to achieve a high compression
      duration is not related to compression rate, and should not be a consideration
      when guidelines on CPR are revised.

PMID- 8867714
TI  - High dose and standard dose adrenaline do not alter survival, compared with
      placebo, in cardiac arrest.
AB  - This trial compared blinded 10 mg aliquots of adrenaline with placebo in 194
      cardiac arrest patients treated in hospital using American Heart Association
      guidelines. In-hospital and out-of-hospital arrests were included. Of the 339
      eligible patients a large proportion (145 (45%)) were not randomised and received
      open 1 mg aliquots of adrenaline. This group is also analysed. Supervising
      physicians gave significant preference for males, patients with no previous
      cardiac history and without multiple organ disease to be given open 1 mg
      adrenaline. Patients in asystole at the time of consideration for entry were
      preferentially placed in the trial group (114 (69%) vs. 170 (88%)) and patients
      in ventricular fibrillation were preferentially given open 1 mg adrenaline (31
      (21%) vs. 24 (12%) P < 0.03). The most beneficial rhythm changes which led to
      survival were sinus rhythm and ventricular tachycardia. Analysis of rhythm
      changes resulting from the dosing showed a significant (P = 0.01) change to a
      beneficial rhythm with 10 mg adrenaline but not for 1 mg adrenaline or placebo.
      This was not reflected by an improvement in immediate survival. No significant
      differences in immediate survival (IS) or hospital discharge (HD) exists between
      open 1 mg adrenaline (IS 14 (9.7%), HD 3 (2%)) or the 10 mg adrenaline (IS 9
      (9.6%), HD 0) vs. placebo (IS 7 (7%), HD 0) trial arms. Patients reaching the
      point of use of adrenaline have a uniformly poor immediate survival (8.8%) and
      hospital discharge rate (0.9%). Dosing with 10 mg or 1 mg adrenaline does not
      influence outcome compared with placebo.

PMID- 8867715
TI  - Resuscitation from cardiac arrest in cats: influence of epinephrine dosage on
      brain recovery.
AB  - The quality of brain recovery after cardiac arrest depends crucially on the speed
      of cardiac resuscitation because the low cerebral perfusion pressure during the
      resuscitation procedure facilitates the development of no-reflow. To accelerate
      return of spontaneous circulation, high dose epinephrine has been recommended but
      the effect on the dynamics of early brain recovery is still unknown. We,
      therefore, studied the dynamics of brain resuscitation after cardiopulmonary
      resuscitation (CPR) with standard and high dose epinephrine using non-invasive
      NMR techniques. Fifteen min cardiac arrest was induced in normothermic cats by
      ventricular fibrillation. CPR was performed using an inflatable pneumatic vest
      for cyclic chest compression. With the beginning of CPR the standard dose group
      received 0.02 mg/kg epinephrine (n = 6) and the high dose group received 0.2
      mg/kg (n = 8). Brain recovery was monitored by magnetic resonance imaging of the
      apparent diffusion coefficient (ADC) of water for 3 h. Although high dose
      epinephrine treatment led to a significantly higher blood pressure during early
      reperfusion, rapidly changing heterogeneities of early brain recovery were
      observed in both groups. High dose epinephrine thus does not improve the quality
      of post-cardiac arrest brain recovery during the first 3 h of reperfusion.

PMID- 8867717
TI  - Images in clinical medicine.

PMID- 8867716
TI  - Tracheal rupture after emergency intubation during cardiopulmonary resuscitation.
AB  - We describe a case of tracheal rupture following an emergency intubation during
      cardiopulmonary resuscitation. This complication occurring during resuscitation
      has not apparently been reported previously. Possible causes during the
      management of cardiac arrest are discussed with references to previously
      described cases of tracheal rupture.

PMID- 8867718
TI  - Register of lay use of advisory defibrillators in Europe.

PMID- 8867719
TI  - Cardiac effects of methylmethacrylate in the rat heart-lung preparation with or
      without volatile anesthetics.
AB  - We have assessed the deleterious effects of methylmethacrylate (MMA) on cardiac
      function and metabolism in the isolated heart-lung preparation with or without
      volatile anesthetics. Wistar rats were prepared for the heart-lung model. They
      were randomly divided into 5 groups as follows. (1) Control (C) group. (2) Cement
      (M) group; they received MMA. (3) Halothane (H) group; they received MMA and 1%
      halothane. (4) Isoflurane (I) group; they received MMA and 1.5% isoflurane. (5)
      Sevoflurane (S) group; they received MMA and 2.5% sevoflurane. MMA 1000
      micrograms/ml was administered 7 min after the start of perfusion except in the C
      group. At the end of the experimental period, the hearts were freeze-clamped and
      then myocardial high energy phosphates, lactate and glycogen were measured.
      Cardiac output in all groups but C group decreased significantly. PO2 of the
      perfusion blood in the M, H, I and S groups was significantly lower than that in
      the C group. Myocardial ATP in the M, H, I and S groups was significantly lower
      than that in the C group. ADP and AMP in the M, H, I and S groups were higher
      than those in the C group. There were no significant differences in lactate and
      glycogen levels between the 5 groups. MMA 1000 micrograms/ml is much higher than
      the blood level (0.05-31.89 micrograms/ml) which was reported in clinical
      patients who had femoral prosthesis. Therefore, the direct contribution of MMA
      itself to cardiac depression may be less than the other factors such as embolism
      in clinical situations. Volatile anesthetics did not influence the deleterious
      effects of MMA on cardiac function and metabolism.

PMID- 8867720
TI  - Chromosomal abnormalities and oncogenes.
AB  - The alterations of transcription factor genes by chromosomal translocations play
      an important role in leukemogenesis and lymphomagenesis. The alterations are
      classified into two groups. One is the chimeric gene formation, and the other is
      the aberrant expression without structural changes. The former type is associated
      with the chromosomal translocations found in acute myeloid leukemia, such as the
      AML1/MTG8 in t(8;21) and PML/RAR alpha in t(15;17). The latter is the main
      mechanism in the gene activations observed in acute lymphoblastic leukemia and
      lymphoma. Many transcription factor genes are activated by the recombination with
      the immunoglobulin genes in B cell malignancies or T cell receptor genes in T
      cell malignancies. We isolated the AML1/EVI-1 fusion gene generated by the
      t(3;21) translocation, which is usually found in blastic crisis of chronic
      myelocytic leukemia. The chimeric transcription factor encoded by the fusion gene
      has dual functions, namely differentiation block and stimulation of
      proliferation. These findings provide new insight into the molecular mechanism in
      leukemogenesis by the chimeric transcription factors.

PMID- 8867721
TI  - Study of the collection and separation of umbilical cord blood for use in
      hematopoietic progenitor cell transplantation.
AB  - Human umbilical cord blood has been used as an alternative source of cells for
      repopulating bone marrow in allogenic bone marrow transplantation in children.
      The number of transplantations of umbilical cord blood cells is increasing
      worldwide. Umbilical cord blood was collected from 52 subjects at a single
      collection at the time of delivery, and separated using the red blood cell
      sedimentation technique. Nucleated cells harvested from the fraction enriched
      with white blood cells were used for an assay to detect colony-forming unit
      granulocyte-macrophage (CFU-GM) derived cell colonies and a flow cytometric
      analysis of CD34+ cells under variable conditions. The number of hematopoietic
      progenitor cells that might be reconstituted to bone marrow was estimated. The
      mean duration time from the beginning of delivery to complete collection of cord
      blood was 9.9 min (range 5 to approximately 20 min). The mean volume of umbilical
      cord blood for the 52 collections was 69.1 ml (range 15-135 ml), containing
      1.001% CD34+ cells (range 0.21% approximately 2.63%) and 4 x 10(5) cells of CFU
      GM derived colonies (range 0.2 x 10(5) approximately 10.0 x 10(5) cells) within
      24 h at 4 degrees C after delivery of the infant. There was no contamination by
      the mother's lymphocytes according to cytogenetic analysis using pYNH24, which is
      a probe with a variable number of tandem repeat markers. These findings indicated
      that umbilical cord blood can be easily collected using the syringe method and
      separated by the red blood cell sedimentation technique using 6%
      hydroxyethylstarch. Within 24 h at 4 degrees C, hematopoietic progenitor cells
      were well detected using an assay for CFU-GM derived colonies and were measured
      by flow cytometric analysis. However, the instability of the number of
      hematopoietic progenitor cells must be resolved for safe transplantation of
      hematopoietic progenitor cells as a source of cells for repopulating bone marrow
      in children.

PMID- 8867722
TI  - Serum ferritin in Danes: studies of iron status from infancy to old age, during
      blood donation and pregnancy.
AB  - Iron status and body iron reserves were examined in a broad spectrum of the
      Danish population, and sex- and age-related changes determined. Serum ferritin
      concentration was employed as an indicator of mobilizable body iron stores. The
      relationship between serum ferritin and histochemical assessment of stainable
      bone marrow haemosiderin iron was examined in healthy individuals, defining
      threshold values for serum ferritin indicating exhausted, small, normal, ample,
      and increased iron stores. The populations examined comprised 7241 randomly
      selected normal individuals with an age distribution ranging from newborn to 85
      years old. The influence of factors having a significant impact on iron balance,
      e.g., menstruation, pregnancy, parity, and blood donation, was analysed
      separately. Newborns had high cord serum ferritin levels, which were to a certain
      extent dependent on the mother's iron status. Newborns of mothers taking iron
      supplementation during pregnancy had higher cord serum ferritin than newborns of
      mothers taking a placebo. In children, the serum ferritin level was relatively
      constant from 3 years of age until adolescence, where the prevalence of exhausted
      iron stores was 13% in boys and 18% in girls. In postadolescent men, there was a
      gradual increase in serum ferritin levels until 30 years of age. Subsequently,
      serum ferritin remained relatively constant until old age. Among 30- to 70-year
      old men, 9.4% had ample iron stores. The prevalence of depleted iron stores was
      1.4%, and of iron deficiency anaemia 0.24%. In women, serum ferritin levels
      remained low from adolescence until the menopause. Among 30- to 50-year-old
      premenopausal women, the prevalence of ample iron stores was 0.49%, whereas 18%
      had exhausted iron reserves and 2.6% had iron deficiency anaemia. After
      menopause, serum ferritin gradually rose and approached male levels. Among 60- to
      70-year-old postmenopausal women, 3.0% had ample iron stores, 2.3% had depleted
      stores and none had iron deficiency anaemia. In fertile women, the choice of
      contraception had a significant influence on the iron loss at menstruation.
      Hormonal contraception reduced iron loss, whereas the use of intrauterine devices
      increased iron loss. These effects were reflected in the serum ferritin levels of
      menstruating women. In a placebo-controlled study of iron supplementation during
      pregnancy, serum ferritin levels displayed a characteristic fall both in placebo-
      and iron-treated women. Among placebo-treated pregnant women at term, 19% had
      depleted iron reserves and 12% had iron deficiency anaemia, and among iron
      treated women, 3% had depleted iron stores and none had iron deficiency anaemia.
      In non-pregnant women, there was a significant inverse relationship between
      parity and serum ferritin. Blood donation had a marked influence on the serum
      ferritin level in the adult population. Among Danes, 20-60 years of age, 27% of
      men, 15% of premenopausal and 10% of postmenopausal women were blood donors. In
      all three groups, the prevalence of depleted iron depots was higher in donors
      than in non-donors. Among premenopausal female blood donors, 31.7% had depleted
      iron reserves and 3.3% iron deficiency anaemia. In general, Danish men and
      postmenopausal women had a satisfactory iron status. Adolescent Danish girls and
      premenopausal women had a high prevalence of iron deficiency, which should be
      taken into consideration when establishing guidelines and recommendations for
      nutritional iron intake in this section of the population.

PMID- 8867723
TI  - Serotonin uptake, storage and metabolism in megakaryoblasts.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) uptake, storage and metabolism in human
      megakaryoblastic cell line (Meg-01) which acts as a model for megakaryocyte
      precursors, megakaryoblasts were investigated by using biochemical (HPLC) and
      morphological (electron microscope, EM) techniques. Results showed that Meg-01
      cells were able to take up 5-HT. The intracellular 5-HT level was 2.8 +/- 0.4 and
      51.8 +/- 4.9 (1 h) or 59.0 +/- 4.4 (2 h) ng/10(6) cells, before and after
      incubation with 5-HT, respectively, but no dense bodies were visualized after
      incubation with excess 5-HT by electron microscope observation. This uptake was
      inhibited by 28% on pre-incubation with fluoxetine and 60% of 5-HT in the cells
      was released on incubation with reserpine. 5-Hydroxyindoleacetic acid (5-HIAA)
      concentration of Meg-01 cells was increased after incubation of the cells with 5
      HT (0 and 17.6 +/- 2.1 or 19.9 +/- 1.9 ng/10(6) cells, before and after
      incubation 1 or 2 h, respectively). The study suggests that: (1) 5-HT uptake
      ability is well established in megakaryocytes precursors, megakaryoblasts and the
      uptake ability is affected by reserpine and fluoxetine; (2) however, the capacity
      to store the amine is not well developed in megakaryoblasts and (3)
      megakaryoblasts may contain monoamine oxidase (MAO) which converts 5-HT to 5
      HIAA.

PMID- 8867724
TI  - Recovery of macromolecular activators of phagocytosis from platelets (MAPP)
      producing and releasing function in stored human platelets.
AB  - Macromolecular activators of phagocytosis from platelets (MAPP) were not released
      from platelets prepared from platelet concentrates (PC) obtained after
      anticoagulation with CPD solution and stored for more than 48 h. The MAPP
      activity which had escaped into the plasma disappeared after 72 h of storage.
      After incubation in dialyzed and Ca(2+)-supplemented plasma prepared from the
      same PC or from fresh peripheral blood, the platelets obtained after storage for
      72 h released both MAPP (l-MAPP and s-MAPP) upon thrombin stimulation. Gel
      filtration studies of the plasma revealed that l-MAPP and s-MAPP were produced
      from the platelets incubated in plasma fractions corresponding to l-MAPP and s
      MAPP, respectively. These observations suggest that platelets accumulate
      precursors of MAPP, pre-MAPP comprising pre-l-MAPP and pre-s-MAPP, in the
      presence of Ca2+, and produce and release MAPP when stimulated with thrombin.

PMID- 8867726
TI  - Myelodysplastic changes in three cases within 100 days after allogeneic bone
      marrow transplantation.
AB  - Three patients with severe aplastic anemia, acute promyelocytic leukemia (M3) and
      chronic myelogenous leukemia, developed myelodysplastic changes with trilineage
      morphological abnormalities in a few months following allogenic bone marrow
      transplantation (BMT). Morphologically dysplastic changes associated with
      moderate-severe anemia, leukopenia and/or thrombocytopenia appeared on day 40,
      day 62 and day 68 after BMT. A ferrokinetics study clearly showed ineffective
      erythropoiesis in one patient. Hematopoietic cells were shown to be of donor
      origin in all three cases. The levels of vitamin B12 and folic acid were normal.
      Laboratory tests showed no signs of hemolysis or fragmentation of red blood
      cells. Although the cause of aberrant hematopoiesis compatible with MDS within
      100 days post-BMT remains to be determined, cytomegalovirus infection,
      ganciclovir and/or graft-versus host disease (GVHD) might be associated with this
      myelodysplasia following allogeneic BMT.

PMID- 8867725
TI  - Autoimmune hemolytic anemia in allergic granulomatous angitis (Churg-Strauss
      syndrome).
AB  - We describe a patient with allergic granulomatous angitis who developed
      autoimmune hemolytic anemia (AIHA). A 44-year-old male had been suffering from
      bronchial asthma. On admission, laboratory tests revealed the presence of severe
      eosinophilia (21,500/microliters), elevation of total immunoglobulin E (IgE),
      high lactic dehydrogenase (LDH) and low haptoglobin levels, in addition to
      moderate reticulocytosis. During admission, the patient showed almost
      simultaneous occurrence of vasculitis in the extremities, severe hemolysis and
      exacerbation of asthma in relation to the progression of eosinophilia. Both IgM
      and IgG autoantibodies were considered to be responsible for hemolysis.
      Interestingly, serum levels of interleukin-4 (IL-4) and IL-5 were increased in
      association with eosinophilia and increased IgE production. These findings
      suggest that the AIHA in this patient is mediated or enhanced at least partly by
      high IL-4 and IL-5 production. Although AIHA in this syndrome is very rare, it
      should be considered as a clinical manifestation.

PMID- 8867727
TI  - Cyclosporine-related encephalopathy following allogeneic bone marrow
      transplantation.
AB  - A 46-year-old man with chronic myelogenous leukemia received allogeneic bone
      marrow transplantation (BMT) from a partially human leukocyte antigen (HLA)
      mismatched sibling. Cyclosporine (CYA)-related encephalopathy developed on days
      10 and 21 following BMT, and CYA-related thrombotic thrombocytopenic purpura
      (TTP) developed on day 45 following BMT. We measured serum concentrations of
      thrombomodulin (TM) as a marker of endothelial injury. The concentrations of TM
      were increased during the encephalopathy or TTP and decreased following recovery.
      Since CYA can cause endothelial injury, we suggest that CYA-induced endothelial
      injury is common to the pathogenesis of both the encephalopathy and the TTP. CYA
      therapy should be reinstituted with extreme caution in patients with a past
      history of CYA-related encephalopathy, since readministration of a low-dose CYA
      can evoke the immediate return of the encephalopathy.

PMID- 8867728
TI  - Cyclosporin-responsive pancytopenia and HLA class II alleles of a patient with
      paroxysmal nocturnal hemoglobinuria.

PMID- 8867729
TI  - Sticky fingers: Hox genes and cell adhesion in vertebrate limb development.
AB  - During vertebrate limb development, various genes of the Hox family, the products
      of which influence skeletal element identity, are expressed in specific
      spatiotemporal patterns in the limb bud mesenchyme. At the same time, the cells
      also exhibit 'self-organizing' behavior--interacting with each other via
      extracellular matrix and cell-cell adhesive molecules to form the arrays of
      mesenchymal condensations that lead to the cartilaginous skeletal primordia. A
      recent study by Yokouchi et al. establishes a connection between these phenomena.
      They misexpressed the product of the Hoxa-13 gene in chick limb buds and
      demonstrated both skeletal pattern perturbations and changes in cell-cell
      adhesivity in mesenchyme aberrantly expressing this protein.

PMID- 8867730
TI  - Expanded glutamines and neurodegeneration--a gain of insight.
AB  - Glutamine repeat expansion has been established as the mutation underlying five
      inherited neurodegenerative diseases. The mechanism by which this apparently
      universal mutation, in ubiquitously expressed proteins, causes highly selective
      neurodegeneration is unknown. The proteins containing the glutamine expansions
      are otherwise unrelated and likely to have different functions. Two recently
      published papers provide evidence of a conformational change occurring in
      polyglutamine expansions, which may allow novel interactions and is consistent
      with a toxic gain-of-function hypothesis. HAP1, a protein that interacts with
      huntingtin (Huntington's disease protein), has an expression profile that
      intriguingly mirrors the selective neurodegeneration seen in Huntington's
      disease.

PMID- 8867731
TI  - Myosin II function in non-muscle cells.
AB  - Amongst the remarkable variety of motility that cells display, cytokinesis (cell
      division) is particularly striking. Dramatic changes in cell shape occur before,
      during and after cytokinesis. Myosin II is implicated in the 'rounding up' of
      cells prior to cytokinesis, and is essential in the formation of the contractile
      cleavage furrow during cytokinesis. Now it appears that myosin II plays a role in
      all stages of cytokinesis, as a recent report suggests that myosin II drives post
      mitotic cell spreading. A similar type of motile mechanism operating in cell
      spreading may occur in other cell types in other situations.

PMID- 8867732
TI  - The role of MCM proteins in the cell cycle control of genome duplication.
AB  - The regulatory mechanism which ensures that eukaryotic chromosomes replicate
      precisely once per cell cycle is a basic and essential cellular property of
      eukaryotes. This fundamental aspect of DNA replication is still poorly
      understood, but recent advances encourage the view that we may soon have a
      clearer picture of how this regulation is achieved. This review will discuss in
      particular the role of proteins in the minichromosome maintenance (MCM) family,
      which may hold the key to understanding how DNA is replicated once, and only
      once, per cell cycle.

PMID- 8867733
TI  - The role of thymidylate synthase as an RNA binding protein.
AB  - Thymidylate synthase plays a central role in the biosynthesis of thymidylate, an
      essential precursor for DNA biosynthesis. In addition to its role in catalysis
      and cellular metabolism, it is now appreciated that thymidylate synthase
      functions as an RNA binding protein. Specifically, thymidylate synthase binds
      with high affinity to its own mRNA, resulting in translational repression. An
      extensive series of experiments has been performed to elucidate the molecular
      elements underlying the interaction between thymidylate synthase and its own
      mRNA. In addition to characterization of the underlying cis- and trans-acting
      elements, recent studies have shown that thymidylate synthase has the capacity to
      bind specifically to other cellular RNA species. While the biological
      significance of these other RNA/thymidylate synthase interactions remains to be
      defined, this work suggests a potential role for TS in coordinately regulating
      several critical aspects of cellular metabolism.

PMID- 8867735
TI  - Kinesin proteins: a phylum of motors for microtubule-based motility.
AB  - The cellular processes of transport, division and, possibly, early development
      all involve microtubule-based motors. Recent work shows that, unexpectedly, many
      of these cellular functions are carried out by different types of kinesin and
      kinesin-related motor proteins. The kinesin proteins are a large and rapidly
      growing family of microtubule-motor proteins that share a 340-amino-acid motor
      domain. Phylogenetic analysis of the conserved motor domains groups the kinesin
      proteins into a number of subfamilies, the members of which exhibit a common
      molecular organization and related functions. The kinesin proteins that belong to
      different subfamilies differ in their rates and polarity of movement along
      microtubules, and probably in the particles/organelles that they transport. The
      kinesins arose early in eukaryotic evolution and gene duplication has allowed
      functional specialization to occur, resulting in a surprisingly large number of
      different classes of these proteins adapted for intracellular transport of
      vesicles and organelles, and for assembly and force generation in the meiotic and
      mitotic spindles.

PMID- 8867734
TI  - Touch sensation in Caenorhabditis elegans.
AB  - The nematode C. elegans exhibits a variety of responses to touch. When specific
      sets of mechanosensory neurons are killed with a laser, specific touch responses
      are abolished. Many mutations that result in defective mechanosensation have been
      identified. Some of the mutations define genes that specify the fate of a set of
      mechanoreceptors called the touch cells, which mediate response to light touch to
      the body of the worm. Genes specifying touch cell fate appear to regulate genes
      that encode touch-cell differentiation proteins, including apparent subunits of a
      touch-cell-specific ion channel, rare mutant forms of which lead to swelling and
      lysis of the touch cells. Molecular attachments of the ion channel, both to
      extracellular matrix components and, intracellularly, to a special large-diameter
      microtubule, may be required for mechanical gating of the channel. A
      mechanoreceptor-interneuron-motorneuron reflex circuit for response to light
      touch has been proposed.

PMID- 8867736
TI  - UV damage and repair mechanisms in mammalian cells.
AB  - The formation of DNA photoproducts by ultraviolet (UV) light is responsible for
      induction of mutations and development of skin cancer. To understand UV
      mutagenesis, it is important to know the mechanisms of formation and repair of
      these lesions. Cyclobutane pyrimidine dimers and (6-4)photoproducts are the two
      major classes of UV-induced DNA lesions. Their distribution along DNA sequences
      in vivo is strongly influenced by nucleosomes and other DNA binding proteins.
      Repair of UV photoproducts is dependent on the transcriptional status of the
      sequences to be repaired and on the chromatin environment. Sensitive techniques
      are now available to study repair of UV damage at the level of nucleotide
      resolution in mammalian cells. With the aid of in vitro systems, the entire
      nucleotide excision repair process has been reconstituted from purified protein
      components with naked DNA as a substrate. Future work will focus on the
      development of in vitro assays for transcription-coupled repair and repair in
      chromatin.

PMID- 8867737
TI  - Polarised membrane traffic in hepatocytes.
AB  - The liver was used widely in early studies of polarised transport but has been
      largely overlooked in recent years, mostly because of the development of
      epithelial cell lines which provide more tractable experimental systems. The
      majority of membrane proteins and lipids reach the hepatocyte apical membrane by
      transcytosis and it remains unclear whether there is a direct route for apical
      targeting, although the pathways present have yet to be fully characterised. The
      recent development of systems that allow hepatocyte transport processes to be
      studied in culture and the observation that transcytosis can be significantly
      stimulated under physiological conditions suggest that hepatocytes have a role to
      play in future studies of polarised transport. This review discusses the known
      features of polarised membrane traffic in hepatocytes and contrasts them with the
      characteristics of vesicular transport in other epithelial cell types.

PMID- 8867738
TI  - CAC--the neglected repeat.
AB  - It is becoming increasingly clear that repetitive DNA is of biological
      significance as well as experimental importance. Here we review the information
      available about one type of repetitive DNA, the trinucleotide repeat (CAC)n, and
      briefly compare it with other trinucleotide repeats. Although much work has been
      done in analysing DNA fingerprinting patterns produced using the synthetic
      oligonucleotide (CAC)5 as a probe, there is relatively little information about
      individual (CAC)n-containing sequences and their abundance, organisation and
      distribution in mammalian DNA. From the data that is available, it is clear that
      there are at least two areas that should repay further study: (1) the
      organisation and generation of long sequences that contain (CAC)n motifs as part
      of a larger repeating unit (minisatellites) and (2) the distribution of small
      (CAC)n sequences (microsatellites), in particular their relationship to genes.

PMID- 8867740
TI  - Common ground plans in early brain development in mice and flies.
AB  - Comparing expression patterns of orthologous genes between insects and
      vertebrates, we have recently proposed that the ventral nerve cord in insects may
      correspond to the dorsal nerve cord in vertebrates. Here we show that the early
      development of the insect and vertebrate brain anlagen is indeed very similar.
      Insect and vertebrate brains express similar sets of genes in comparable areas
      with similar functions in the adult. In addition, early axogenesis establishes
      surprisingly similar patterns of axonal connectivity in both groups. We therefore
      propose that insect and vertebrate brains are built according to a common ground
      plan, and that specific areas of the insect and vertebrate brains be considered
      as homologous, meaning that these areas already existed, with their specific
      functions, in their common ancestor.

PMID- 8867739
TI  - Deregulation of protein synthesis as a mechanism of neoplastic transformation.
AB  - Early research on the cell cycle revealed correlations between protein
      accumulation and cell proliferation. In this review, I describe the data showing
      that abnormality of cell growth and tumor development are dependent upon oncogene
      induced increases in the levels and activity of factors that determine the rate
      of protein synthesis. It is proposed that the establishment of a vicious circle,
      namely oncoproteins-->increase in translation-->oncoproteins, is a major
      biological mechanism that fuels neoplastic growth. The constitutively high rates
      of protein synthesis and accumulation of proteins, including those necessary for
      DNA replication and mitosis, would drive cells to excessive proliferation.

PMID- 8867741
TI  - [Follow-up of mastoiditis and mastoidectomy].
AB  - BACKGROUND: To analyse the late results of mastoiditis and operative intervention
      as well as critical classification of our own indication for operation we invited
      298 operated patients to follow-up examinations. PATIENTS AND METHODS: 218 of 298
      patients operated on, took part in these examinations. The follow-up time ranged
      between 2 and 18 years. RESULTS: Altogether 311 ears were operated. Out of these,
      69 patients had presented with classical mastoiditis and 242 with "masked" type.
      Microscopic examination of the operated ears showed that 284 (91.3%) had normal
      tympanic membranes, 13 (4.2%) had central tympanic membrane perforations with
      mucosal inflammation and 14 (4.5%) had residual retraction pockets or attic
      cholesteatomas. Hearing tests showed that 242 (77.8%) were normal, 56 (18%) had
      conductive deafness (with 32 of these ears having normal tympanic membranes), 10
      (3.2%) had sensorineural deafness and 3 (1%) combined deafness. Schuller's
      radiographic views demonstrated compact mastoid processes in 48.7% of the
      reexamined ears and re-pneumatisation in 53%. CONCLUSION: The presented data of
      our re-examinations support our principle that prompt surgical treatment of all
      forms of mastoiditis is imperative.

PMID- 8867742
TI  - [Intubation damage to the larynx. Manifestations, comments on pathogenesis,
      treatment and prevention].
AB  - BACKGROUND: A variety of lesions can be seen in the larynx subsequent to an
      intubation anaesthesia or treatment with a respirator. The larynx may already be
      injured by introducing an endotracheal tube. The inserted tube must necessarily
      chafe the laryngeal mucosa. Many studies are concerned with individual
      manifestations [5-10,14,16,17,20]. The following article gives an overview of the
      intubation lesions of the larynx observed by us and offers comments on
      pathogenesis and prevention. PATIENTS: 161 patients with severe lesions
      subsequent to an intubation or treatment with a respirator were seen at the ENT
      Department of the University of Marburg Hospital from 1973 to 1995. TYPES OF
      LESIONS CAUSED BY INTUBATION: Basing on the pathomechanisms, we can classify the
      lesions as follows: inflammatory reactions, lesions of the larynx caused during
      intubation, lesions caused by chafing by the tube or by the sealing sleeve.
      CONCLUSIONS: Considering the large number of performed intubations, lesions of
      the larynx occur rarely. However, in view of the possible sequels, it would be
      advisable if an experienced laryngologist would perform a careful endoscopic
      examination of the larynx and trachea at least after every forced or prolonged
      intubation and especially after every treatment with a respirator.

PMID- 8867743
TI  - [Fatal complications in tracheotomized children].
AB  - BACKGROUND: Tracheotomy in the pediatric patient has become a routine procedure
      since the late 19th century, when it was used in treating diphtheria. Although
      underlying diseases have changed, the child with an artificial airway still faces
      numerous risks. This study investigates fatal complications in 280 patients with
      tracheostomy who were seen in the Dr. von Haunersches Kinderspital for laryngo
      tracheo-bronchoscopy. METHOD: Data was acquired from patients' records of the Dr.
      von Haunersches Kinderspital and communications with other institutions. RESULTS:
      Nineteen deaths were investigated. Three patients died of acute cannula
      obstruction although hospitalized in different institutions. Two patients who
      died at home may also have suffered cannula obstruction, although this could not
      be verified. The majority of patients succumbed to the underlying disease.
      CONCLUSIONS: Permanent close supervision or monitoring at all times is critical
      to prevent cannular related deaths. Our results are compared with major series in
      other studies. In addition, we propose a booklet for the pediatric tracheotomy
      patient to document patient data and examination findings, e. g. type and size of
      cannula, duration of cannulation, laryngotracheometry, and complications. Its
      purpose will be to support communication between patients, parents,
      pediatricians, pediatric surgeons, and otolaryngologists. Furthermore, this
      booklet will help in evaluating risks, which may encounter pediatric tracheostomy
      patients, thereby enabling future studies.

PMID- 8867744
TI  - [Short tau inversion recovery fat suppression in T2-weighted turbo spin echo-MRI
      of malignancies of the mouth and oropharynx].
AB  - BACKGROUND: T1-weighted sequences before and after the application of contrast
      medium and T2-weighted sequences are used for magnetic resonance imaging of
      malignomas of the oral cavity and the oropharynx. The authors studied the utility
      of short tau inversion recovery fat suppression (STIR) in T2-weighted turbo spin
      echo sequences (TSE). METHODS: Twenty patients with malignomas of the oral cavity
      and oropharynx were examined on a 1.0 Tesla magnetom using T2-weighted TSE
      sequences with and without STIR as well as T1-weighted spin echo sequences before
      and after the application of contrast medium. RESULTS: STIR was successfull in
      all patients. STIR worsened the signal-noise-ratio significantly, but improved
      tumor delineation compared to T2-TSE without fat suppression in 75% according to
      three different investigators. CONCLUSION: The STIR technique is beneficial for
      the progress in diagnostic imaging of cancer of the oral cavity and oropharynx.

PMID- 8867745
TI  - [Estrogen feedback tests in women with laryngeal carcinomas].
AB  - BACKGROUND: The high incidence ratio males to females is the reason for
      considering a hormonal dependency of these tumours for many years. The low
      incidence of laryngeal cancer in women has generally been suggested as being due
      to "oestrogen defense". Although we do have some circumstantial evidence in the
      meantime, no final evidence on this topic is available so far. METHODS: The
      oestrogen feedback effect could be another more objective parameter to bring more
      light to the research of this question. As one of the regulation mechanisms of
      the hypothalamic-pituitary-adrenal axis the oestrogen feedback mechanism
      represents the regulation of LH and FSH production in the pituitary gland by
      peripheral oestrogens. The mechanism is known to exist lifelong under normal
      conditions. Whereas the positive oestrogen feedback is typical for women, a
      negative response pattern is mostly found in men. The positive response pattern
      is characterised by increasing LH values, higher than the starting level, on the
      3 th and 4 th day after intravenious application of oestrogens. RESULTS: The
      results of the present investigation show some difference. 5 of 6 examined women
      with laryngeal cancer were found to have a clearly negative oestrogen feedback,
      whereas 4 of 5 healthy women had a positive oestrogen feedback effect. 5 healthy
      men showed the typical negative effect for men. CONCLUSION: We may assume a
      narrow relationship between the male regulation type and the occurrence of
      laryngeal cancer in women, if further trials including more patients are able to
      reproduce these results.

PMID- 8867746
TI  - [Ultrasound measurement of skin and cartilage thickness in healthy and
      reconstructed ears with a 20-MHz ultrasound device].
AB  - BACKGROUND: The surgical reconstruction of the external ear according to Weerda
      is a proven method to correct malformed or amputated auricles. Our goal was to
      test the usefulness of high-frequency ultrasound in measurement of layer
      thickness of auricles. METHOD: Using a 20-MHz B-Mode ultrasonographic method
      (Dermascan C, adn-Medizintechnik, Hamm, Germany) we measured the thickness of
      skin and cartilage layers in patients with normal auricles (n = 47) and
      reconstructed auricles (n = 15) in vivo. RESULTS: The average thickness of the
      cutis of normal auricles was 0.8 mm, the subcutis and the cartilage layer 0.6 mm
      thick on average. In reconstructed auricles, the thickness of the cutis averaged
      1.0 mm, the subcutis 1.1 mm, and the cartilage layer (to the extent that it could
      be visualized) 3.0 mm. DISCUSSION: The results demonstrate a good approximation
      of the thicknesses of the different layers (cutis and subcutaneous tissue) in
      reconstructed and natural external ears, but the cartilage of the reconstructed
      auricles is clearly thicker. CONCLUSIONS: The 20-MHz B-Mode ultrasound is
      suitable for examining the methods of plastic surgery in malformed auricles.
      Based on the demonstrated results, surgical modifications should be assessed in
      future.

PMID- 8867747
TI  - [What is the value of color-coded duplex ultrasound in diagnosis of head-neck
      tumors].
AB  - BACKGROUND: The aim of the present study is to demonstrate the rating of low flow
      color duplex echography as a new technique in the preoperative staging of head
      and neck cancer. METHODS: Forty-four patients with squamous cell carcinomas of
      the oral cavity, oropharynx, and hypopharynx were examined. Gray scale imaging as
      well as color duplex scan with doppler spectrum quantification were performed on
      each patient using a Siemens Quantum 2000 duplex scan with 7.5 MHz linear array.
      RESULTS: Squamous cell carcinomas of the upper aerodigestive tract as well as
      their metastases are poorly vascularized but show irregular vascular patterns. In
      comparison to gray scale echography estimation of tumor borderline is improved by
      imaging of peripheral tumor vessels. Furthermore, imaging of irregular central
      tumor vessels in metastatic lymphatic nodes renders important information for N
      staging. CONCLUSION: Thus color duplex echography should be recommended for
      routine application in preoperative head and neck tumor staging.

PMID- 8867748
TI  - [The role of color duplex ultrasound in diagnosis and differential diagnosis of
      carotid body tumors].
AB  - BACKGROUND: Currently the diagnosis of tumorous lesions of the carotid
      bifurcation is the domain of magnetic resonance imaging (MRI) and digital
      subtraction angiography (DSA). So far, colour Doppler imaging (CDI) has not been
      playing an important part in this field. The aim of this study was to define the
      diagnostic value of CDI in the evaluation of these tumours related to the big
      arteries and to compare the different imaging techniques. PATIENTS AND METHODS: 6
      female patients with suspected tumours of the carotid bifurcation were examined
      with CDI. Additionally 5 MRI examinations and 3 preoperative diagnostic DSA
      examinations were performed in the same patients. Pathologically, there were 4
      typical carotid body tumours, 1 neuroma of the sympathetic trunk and 1 multifocal
      paraganglioma of the neck. RESULTS: In carotid body tumours we found a
      characteristic broadening of the bifurcation with shifting of the internal
      carotid artery posteriorly and laterally and of the external carotid artery
      anteriorly and medially. The highly vascularized tumour is surrounded by the
      arteries. This combination of ultrasound findings was absent in cases of
      sympathetic neuroma and multifocal paraganglioma. No additional information was
      achieved with MRI and DSA. CONCLUSION: CDI and MRI evaluation revealed the same
      diagnostic value in cases of vascularised tumours of the carotid bifurcation. CDI
      proved to be as accurate as DSA in the imaging of the big arteries and their
      relationship to the tumour, as well as of the small tumour feeding vessels.
      Therefore DSA may be omitted as an invasive diagnostic tool in the diagnosis of
      carotid body tumours.

PMID- 8867749
TI  - [In vitro cultivation of human chondrocytes using autologous human serum
      supplemented culture medium: minimizing possible risk of infection with pathogens
      of prion diseases].
AB  - BACKGROUND: The in vitro engineering of autologous transplant might play an
      important role in reconstructive surgery in the near future. The amplification of
      isolated cells is an important part of the engineering. Because of the use of
      fetal calf serum (fcs) in the cellculture, there is a potential risk of
      transmission of prion diseases. The aim of this study was to evaluate a way of
      amplifying chondrocytes with autologous human serum instead of fcs and to compare
      the rates of proliferation. METHODS: For this purpose the isolated chondrocytes
      were cultured using complete medium, with 10% fcs or 10% autologous human serum
      being added to the medium. RESULTS: The experiments show that a culture with
      complete medium and autologous human serum allows a 150 to 300fold increase in
      the number of cells after 40 days of culture and the proliferation is up to 3fold
      higher than in cultures using fcs. DISCUSSION: Chondrocytes can be stimulated by
      autologous human serum to proliferate. It is possible to avoid fcs in the culture
      of chondrocytes and to minimize the risk of an infection with prions.

PMID- 8867750
TI  - [Damage to sense of smell and taste following xylocaine administration? Process
      before the expert evaluation committee for medical malpractice of the North Rhine
      Physicians Organization in 1995 (Az. 91/588)].

PMID- 8867751
TI  - [Nosebleed in the history of rhinology. Images of the history of
      otorhinolaryngology presented by instruments from the collection of the
      Ingolstadt Medical History Museum].
AB  - ETIOLOGY AND ANATOMY: Up to the Middle Ages, nosebleeds were considered a natural
      means of purification in internal diseases. In addition injuries, extreme
      physical exertion, and influences from the sexual sphere were recognized causes.
      In the 19th century, low atmospheric pressure on mountains and in balloons was
      also assumed to be an etiological factor. It was only at the end of the 19th
      century that the importance of high blood pressure and defective coagulation were
      diagnosed in context with nosebleeds. In ancient times, it was known that
      compressing the nasal alae can often stop the bleeding, but that blood may as
      well run down the throat and mimick a hemorrhage coming from the trachea. Between
      1874 and 1884, several authors, among them J. L. Little in USA and W. Kiesselbach
      in Germany, recognized the anterior part of the nasal septum as a frequent
      location of bleeding. GENERAL THERAPY AND ANTERIOR NASAL PLUGGING: General
      measures of hemostasis recommended already in ancient times were the application
      of cold and diverting the blood to other regions of the body by applying
      tourniquets to legs and arms, or by cupping. Anterior nasal plugging was already
      known to the ancient Assyrians and Hippocrates. Scribonus Largus (1st century)
      was the first to describe a nasal plugging around a tube, thus preserving a
      patient respiratory passage. During the Middle Ages local application of
      assumedly hemostatic substances of the apothecary of that time played an
      important part, among them "cranial moss", the lichen that grew on the skulls of
      hanged corpses exposed to the weather for a long time, and "mumia", a black
      unctuous substance made of Egyptian mummies. Plugging the nares with an inflated
      balloon, fabricated from animal intestines, was described first by J. P. Frank in
      1807. During the second half of the 19th century, numerous varieties of rubber
      balloons, rubber caps, and condoms came in use for this technique. The first
      nasal balloon combined with a respiratory tube was presented by Dionisio in 1890.
      POSTERIOR NASAL PLUGGING: Plugging of the posterior nares was anticipated by
      Hippocrates technique of removing a pendulous polyp by pulling a sponge tied to
      four strings backwards through the nasal cavity. Le Dran, surgeon in Paris in
      1731, was the first to adopt this technique for stopping a nasal hemorrhage. The
      instrument named after Belloc (or Belloq) for placing a posterior nasal plug
      consists of a metal tube in which a curved spring can be pushed forwards and
      backwards. The first description of this instrument remains a mystery. There were
      at least two French surgeons named Belloc and Belloq, and this has been the
      source of some confusion. A paper of a certain Belloq of 1757, which is generally
      regarded as the source, deals with means of stopping certain hemorrhages. It
      exists in two different printed versions with identical wording and describes the
      application of candle wax for stopping severe hemorrhages after tooth extraction
      and abdominal puncture; however, it makes no mention of nosebleeds. Bellocq's
      tube was made known by Deschamps' book on diseases of the nose in 1804. For about
      150 years, it was one of the instruments most frequently illustrated in textbooks
      and most rarely used in practice because surgeons generally preferred a simple
      catheter for placing a posterior nasal plug. The article concludes with a short
      survey of the history of chemical and thermal cauterisation and ligation of blood
      vessels for stopping nosebleeds.

PMID- 8867752
TI  - Occlusion edge blur: a cue to relative visual depth.
AB  - We studied whether the blur/sharpness of an occlusion boundary between a sharply
      focused surface and a blurred surface is used as a relative depth cue. Observers
      judged relative depth in pairs of images that differed only in the blurriness of
      the common boundary between two adjoining texture regions, one blurred and one
      sharply focused. Two experiments were conducted; in both, observers consistently
      used the blur of the boundary as a cue to relative depth. However, the strength
      of the cue, relative to other cues, varied across observers. The occlusion edge
      blur cue can resolve the near/far ambiguity inherent in depth-from-focus
      computations.

PMID- 8867753
TI  - Uncertainty experiments support the roles of second-order mechanisms in spatial
      frequency and orientation discriminations.
AB  - Previous studies of spatial frequency and orientation discrimination [Vision Res.
      32, 1885 (1992)] suggest the existence of two second-order cortical mechanisms:
      one that mediates spatial frequency discriminations and sums signals across
      orientations and one that mediates orientation discriminations and sums signals
      across spatial frequency bands. The existence of each mechanism is tested in an
      uncertainty experiment in which the observer does not know which of two
      hypothetically pooled signals deviates from the standard but must judge whether
      the deviation is an increment or a decrement. No uncertainty effect is expected
      if the signals are completely pooled. Observed effects are compared with this
      expectation and with both theoretical and empirical estimates of the effects
      expected if the signals are processed separately. Results support the existence
      of the first mechanism, but not its exclusive role in mediating spatial frequency
      judgments, and support the exclusive role of the second mechanism in mediating
      orientation judgments.

PMID- 8867754
TI  - Effect of window size on detection acuity and resolution acuity for sinusoidal
      gratings in central and peripheral vision.
AB  - Detection and resolution of square patches of sinusoidal gratings were measured
      in central and peripheral vision (30 degrees horizontal temporal visual field)
      for high-contrast gratings as a function of the number of cycles in the stimulus.
      We determined performance in a forced-choice paradigm for a fixed number of
      stimulus cycles by arranging for stimulus diameter to vary inversely with spatial
      frequency. For both psychophysical tasks and for both target locations, the
      psychometric function relating performance to log spatial frequency shifted to
      higher frequencies without changing slope significantly as the number of cycles
      in the stimulus was increased. Thus the entire effect could be captured by an
      analysis of spatial acuity, which increased with increasing number of grating
      cycles over the range 0.5-6 cycles but remained constant over the range 6-14
      cycles. In the central field, resolution acuity and detection acuity were equal
      regardless of the number of cycles in the stimulus. In the peripheral field,
      detection acuity exceeded resolution acuity and perceptual aliasing occurred for
      stimuli in the range 1-14 cycles. From this result we conclude that resolution
      acuity is sampling limited in the periphery, provided that the stimulus contains
      at least one full cycle of the grating. Essential features of the results could
      be accounted for by Fourier analysis of the stimulus.

PMID- 8867755
TI  - Loss of sensitivity to motion-defined form in patients with primary open-angle
      glaucoma and ocular hypertension.
AB  - During the past few years many researchers have attempted to find a
      psychophysical test that will identify at an early stage patients at risk for
      developing glaucoma. We investigated the ability of a test of motion-defined (MD)
      form recognition to discriminate between patients with primary open-angle
      glaucoma (POAG) and control subjects and to identify patients with ocular
      hypertension (OHT) at risk for developing glaucoma. Performance on two MD tests
      and three tests of static, luminance-defined (LD) form recognition was compared.
      Speed thresholds for reading MD letters proved to be the most sensitive test of
      early glaucomatous damage. 80% of POAG and 38% of OHT patients were abnormal on
      this test. During a 3-year follow-up period, 50% of these OHT patients developed
      glaucoma. These psychophysical findings support the hypothesis of early motion
      deficits in glaucoma.

PMID- 8867756
TI  - Temporal uncertainty effects on orientation discrimination and stereoscopic
      thresholds.
AB  - If a pattern requiring orientation discrimination was presented randomly in one
      of five clearly demarcated time frames 500 ms apart, orientation thresholds were
      elevated approximately 20% over their values when the time slot was fixed. For
      stereoscopic depth discrimination the disparity threshold elevation was
      approximately 40%.

PMID- 8867757
TI  - In defense of an onset-rime syllable structure for English.
AB  - Many linguists and psycholinguists have suggested that English syllables have an
      onset-rime structure. Pierrehumbert and Nair (1995) have recently argued against
      this view and in favor of the idea that syllables have a moraic structure. We
      show that the results of word game experiments reported by Pierrehumbert and Nair
      are consistent with the onset-rime theory and that there are problems with their
      idea of output templates. Although people may learn about the phonological
      structure of a word game's output when they have a chance to do so, they tend to
      divide syllables at the boundary between the onset and the rime even when they do
      not have the opportunity to memorize a model. Moreover, the results of our recent
      statistical study of the distributions of phonemes in English syllables suggest
      that the rime is a domain for particularly close dependencies among phonemes. We
      conclude that Pierrehumbert and Nair's rejection of the onset-rime model was
      overly hasty and was based on a limited set of data. When a broad range of data
      is considered, the evidence supports the idea that English syllables have an
      onset-rime structure.

PMID- 8867758
TI  - Do English-learning infants use syllable weight to determine stress?
AB  - A linguistic factor governing the assignment of English lexical stress is
      syllable weight. Heavy syllables which have either a long (tense) vowel or are
      closed with a consonant are heavy and automatically bear stress. Are infants
      sensitive to this aspect of the English stress system? Previous research by
      Jusczyk, Cutler, and Redanz (1993) showed that nine-month-olds listened longer to
      words exhibiting Strong-Weak than Weak-Strong stress pattern. However, they did
      not investigate the role of syllable weight in this preference. A series of three
      experiments explored infants' preference for Strong-Weak versus Weak-Strong
      lists, but systematically manipulated the syllable weight of Strong syllables.
      The results suggest that syllable weight is not a necessary component of the
      Strong-Weak preference observed in previous studies. Rather it appears that
      infants prefer both words that begin with a Strong syllable and Strong syllables
      that are heavy. Thus, the results suggest that sensitivity to surface linguistic
      patterns and the principles that underlie them may be independent in early
      language acquisition.

PMID- 8867759
TI  - Coarticulation in slow speech: durational and spectral analysis.
AB  - Durational and spectral measures of anticipatory as well as perseverative
      coarticulation were obtained from the acoustic speech signal of German sentence
      utterances produced by six young female speakers at comfortable and at slowed
      speech rate. The test sentences comprised a systematically varied nonsense word
      embedded into a carrier phrase. Anticipatory and perseverative coarticulation
      were characterized by different patterns of durational and spectral features.
      Inter-speaker variability was considerable, particularly with respect to
      anticipatory vowel-to-vowel coarticulation. As a rule, slowing of speaking rate
      resulted in a decrease of perseverative coarticulation in the presence of
      unchanged anticipatory effects. In conclusion, these data corroborate the
      suggestion that different mechanisms underlie anticipatory and perseverative
      coarticulation.

PMID- 8867760
TI  - Phonological selectivity in the first fifty words of a bilingual child.
AB  - This paper examines the phonology of the first 50-word period of a Portuguese
      Turkish bilingual child (1;7 - 1;10), with specific reference to
      selection/avoidance patterns. Results reveal clear patterns of avoidance related
      to language-independent segmental restrictions (front rounded vowels, back high
      unrounded vowel, initial fricatives, laterals and consonant clusters), and in
      some cases, to word/syllable shapes. Results also show lack of synonymy in his
      productive lexicon and very little variability.

PMID- 8867761
TI  - Dermatofibroma and dermatofibrosarcoma protuberans: an immunohistochemical study
      reveals distinctive antigenic profiles.
AB  - Recent studies of mesenchymal cells of the dermis using antibodies to factor
      XIIIa (FXIIIa) and CD34 have demonstrated immunophenotypic heterogeneity amongst
      the normal resident spindle/dendritic cells of the dermis. These
      immunohistochemical markers also have been reported to be useful in the
      distinction between two dermal mesenchymal tumors of uncertain histogenetic
      origin - the dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP). DFs
      are FXIIIa positive, CD34 negative while DFSPs are FXIIIa negative and CD34
      positive. Expression of CD34 may also have histogenetic implications for these
      cutaneous neoplasms. In order to further study these tumors we studied 13 DFs and
      12 DFSPs immunohistochemically using a microwave antigen retrieval technique in
      formalin fixed, paraffin embedded tissue with antibodies to FXIIIa, CD34, CD45,
      factor VIII related antigen (FVIII-RA), the Ki-67 antigen (MIB-1 antibody) and
      the lectin Ulex europaeus. Of the DFs, all 13 were FXIIIa positive; 12/13 were
      CD34 negative and 1 was strongly CD34 positive. All DFSPs were FXIIIa negative
      and CD34 positive. One DFSP also contained an area of fibrosarcoma which was
      negative for both markers. All tumors were negative with anti-FVIII-RA Ulex
      europaeus, and anti-CD45. MIB-1 staining demonstrated nuclear staining of the
      tumor cells in both DFs and DFSPs. Image analysis of MIB-1 stained sections
      revealed a significant difference in mean percent positive nuclear area between
      DFs (1.16% +/- 0.405) and DFSPs (2.265% +/- 0.963). In summary, FXIIIa reliably
      distinguished between DFs and DFSPs; however, CD34 immunoreactivity can be seen
      in DFs. No evidence for vascular or hematopoietic origin of these tumors was
      found using microwave antigen retrieval and anti-FVIII-RA, Ulex europaeus, or
      CD45 staining. With microwave enhancement trypsin was not necessary for FXIIIa
      staining; however, it did not significantly enhance detection of FVIII-RA, CD45,
      or Ulex antigens. DF and DFSP tumor cells are in the cell cycle as demonstrated
      by MIB-1 staining and there are significant differences in percent positive
      nuclear area between these neoplasms, being higher in DFSP compared to DF.

PMID- 8867762
TI  - Effects of a factor derived from polymorphonuclear leukocytes on the growth and
      collagen metabolism in normal and scleroderma skin fibroblast cultures.
AB  - Effects of a factor (15 kDa) derived from polymorphonuclear leukocytes (PMNs) on
      the growth and collagen metabolism of normal and scleroderma skin fibroblasts in
      culture were investigated. Skin fibroblasts from papillary, reticular or whole
      dermis of 5 patients with scleroderma and 7 normal controls were cultured in the
      presence or absence of PMN factor. The factor affected skin fibroblasts, (i) to
      stimulate cell proliferation, (ii) to stimulate collagenase production as
      observed by its functional activity, but (iii) to suppress collagen production
      with little effect on collagen types at a stage before the translational level.
      Scleroderma fibroblasts were less susceptible to the factor than normal
      fibroblasts in terms of cell proliferation and protein synthesis including
      collagen. Stimulation of cell proliferation by the factor was higher with
      reticular cells than papillary cells, while stimulation of collagenase production
      was inversely high in papillary cells and little stimulation was noted with
      reticular cells. Suppression of collagen production was also eminent in papillary
      cells, compared with that in reticular cells. These results suggest that PMNs
      function at the inflammatory stage in shifting tissue metabolism to a catabolic
      phase by releasing a factor which stimulates connective tissue cells, and that
      decreased susceptibility of scleroderma cells and reticular cells to PMN factor
      may provide for a positive factor in the accumulation of collagen in the
      reticular dermis of scleroderma skin.

PMID- 8867763
TI  - Expression of cutaneous lymphocyte-associated antigen defined by monoclonal
      antibody HECA-452 on human Langerhans cells.
AB  - Cutaneous lymphocyte-associated antigen (CLA) defined by monoclonal antibody
      (MoAb) HECA-452 has been shown to be preferentially expressed on cutaneous T
      cells. The CLA expression has been regarded as a homing molecule of T cells to
      the skin in various inflammatory cutaneous disorders. In this paper we
      investigated the significance of CLA expression on Langerhans cells (LC) and
      found that, in normal skin, some epidermal LC express CLA, and that most dermal
      CD1a positive cells express CLA. When normal skin was organ cultured, the
      percentage of CLA positive cells in LC and dermal CD1a positive cells decreased
      appreciably. In diseased skin, epidermal LC increased in number and most LC
      expressed CLA. Thus, this study suggests that the CLA expression on LC may play
      as a homing molecule of LC to the skin.

PMID- 8867764
TI  - Suppressive effect of staphylococcal enterotoxin B on murine contact
      hypersensitivity.
AB  - Superantigens (SAg) possess the capacity to interact with particular V beta
      regions of T cell receptor (TCR) and major histocompatibility complex (MHC) class
      II molecules, and activate a large number of T cells and accessory cells.
      staphylococcal enterotoxins (SEs) are recently well known as SAg and anticipate
      to modulate immunological reactions. In this study, we investigated the effect of
      staphylococcal enterotoxin B (SEB) on contact hypersensitivity reaction (CHR) to
      2,4-dinitrofluorobenzene (DNFB) in BALB/c mice. SEB-injection inhibited the
      induction of sensitization on CHR. Suppressor cells were not found in the spleen
      or lymph node cells from mice treated with SEB. Normal spleen cells cultured with
      SEB showed significant proliferation and tumor necrosis factor-alpha (TNF-alpha)
      production. CHR was suppressed by intravenous injection of the culture
      supernatant. In addition, anti-TNF-alpha antibodies inhibited the suppressive
      effect induced by the supernatant. These findings indicate that TNF-alpha
      produced by SEB-responding cells inhibits the induction of sensitization on CHR.
      Therefore, SAg may play important roles in the modulation of immune system
      through the stimulation of TNF-alpha production.

PMID- 8867765
TI  - Proliferating cell nuclear antigen (PCNA); prognostic value in the clinical
      recurrence of primary basal cell carcinoma.
AB  - Proliferating cell nuclear antigen (PCNA) is a nuclear protein which is
      correlated with the S-phase of the cell cycle and has been utilized by many
      investigators as a marker of cell proliferation. A previous immunohistochemical
      study revealed increased PCNA staining in clinically and histologically
      aggressive basal cell carcinoma and the present study evaluated the prognostic
      value of PCNA in clinical recurrence of primary basal cell carcinoma. Thirty
      patients with primary basal cell carcinoma (BCC) treated with shave biopsy
      followed by electrodesiccation in 1989 and have been regularly followed up for
      local recurrence were selected for this study. The histology of their primary
      BCC's was reviewed and the presence of PCNA in the tumor cells was studied
      immunohistochemically. Ninety-six percent of the non-recurrent BCC's had < 10% of
      tumor cells showing a positive staining for PCNA whereas 100% of the BCC's that
      recurred showed more than 30% of tumor cells staining positive for PCNA. In
      comparison, 88.9% of the non-recurring group showed non-aggressive histological
      features and only 66.7% of the recurring group was aggressive by microscopic
      appearance. In summary, the PCNA staining appeared to be superior to traditional
      histologic features in predicting clinical recurrence in primary BCC's and
      further prospective studies in a larger patient group are warranted.

PMID- 8867766
TI  - Regulation of keratinocyte growth factor gene expression in human skin
      fibroblasts.
AB  - Human keratinocyte growth factor (KGF) is a recently identified mitogen for
      epithelial cells produced by normal stromal fibroblasts. KGF has been shown to
      stimulate keratinocyte migration and promote re-epithelialization of skin
      suggesting a critical role for KGF in wound healing. To understand how KGF might
      be regulated during wound healing, we examined the ability of the pro
      inflammatory cytokines interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1
      beta) interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) transforming
      growth factor-beta 1 (TGF-beta 1) and interferon-gamma (IFN-gamma) to modulate
      KGF gene expression in cultured human fibroblasts, using northern blot analysis.
      Exposure to IL-1 alpha (20 units/ml) or IL-1 beta (100 units/ml) for 24 h
      increased KGF mRNA expression by 352% and 504%, respectively, with early
      induction seen at 2 h and maximal induction seen at 8 h. TNF-alpha (30 ng/ml)
      increased KGF mRNA expression by 535% at 24 h, with induction first seen at 8 h.
      The maximal induction of KGF mRNA was observed when IL-1 alpha, IL-1 beta and TNF
      alpha were used at 100 units/ml, and 3 ng/ml, respectively, although
      concentrations 100-500-fold lower (IL-1 alpha, 0.02 units/ml; IL-beta, 0.02
      units/ml; and TNF-alpha, 0.03 ng/ml) were nearly as stimulatory, increasing KGF
      mRNA expression by 175%, 254% and 322%, respectively. IL-6 (200 units/ml), TGF
      beta 1 (5 ng/ml) and IFN-gamma (200 units/ml) did not change the level of KGF
      mRNA at 24 h in human fibroblasts under the same conditions. The protein
      synthesis inhibitor cycloheximide abrogated the effects of IL-1 alpha, IL-1 beta
      and TNF-alpha on KGF gene induction, indicating that new protein synthesis is
      required in the process. Dexamethasone (10(-7) M), known to inhibit inflammatory
      reactions and retard wound healing, also inhibited the induction of KGF mRNA
      expression by IL-1 alpha, IL-1 beta and TNF-alpha. Individual variation in KGF
      mRNA expression was see when fibroblasts from different aged donors were
      analysed, but no consistent age-associated change was observed. These results
      suggest that IL-1 alpha, IL-1 beta and TNF-alpha up-regulate KGF gene expression
      in fibroblasts and might be responsible for its induction following skin wounding
      or other injury.

PMID- 8867768
TI  - Use of thrombospondin level to predict the clinical course of atopic dermatitis
      associated with food hypersensitivity or skin infection.
AB  - Plasma thrombospondin (TSP) levels were monitored in patients with atopic
      dermatitis (AD) exacerbated by food hypersensitivity (FH) or skin infection. In
      both groups, the TSP levels correlated positively with skin disease severity
      score from the onset to 2 months after treatment. A sustained TSP level above 250
      ng/ml predicted a 7-fold increase in the incidence of flare-up of AD.

PMID- 8867767
TI  - Production of chemotactic factor(s) of Langerhans cells by lymph node cells in
      contact sensitivity.
AB  - Langerhans cells (LCs) have to leave the epidermis to migrate into the regional
      lymph node (LN) after receiving immunogenic signals in contact sensitivity. There
      should be some molecules responsible for migration of LC in this process. In
      order to determine whether LN cells can generate such regulatory molecules, we
      made a search of such molecules in the culture supernatant of LN cells obtained
      from hapten-painted mice by using a modified Boyden chamber method. The molecule
      of LC chemotaxis appeared in the culture supernatant at 24 h after hapten
      painting and its production declined with time thereafter. Antibodies against
      both ICAM-1 and LFA-1 partially inhibited the chemotactic activity, but this was
      not the case with anti-TNF-alpha antibody, anti-GM-CSF antibody, fibronectin
      RGDS. RGES peptide or laminin. The molecule was heat labile and appeared as a
      molecule of 45-68 kDa on high performance liquid chromatography. Our results
      suggest that LN cells generate one of the chemotactic molecules of LCs, by which
      LC can migrate to the regional LN in contact sensitivity.

PMID- 8867769
TI  - A keratin K14 gene mutation in a Japanese patient with the Dowling-Meara type of
      epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is caused by an aberration of the keratin
      intermediate filaments and recent studies indicated causal mutations in the
      keratin K14 and K5 genes. In this study, we examined keratin K14/5 gene mutation
      in a Japanese patient with EBS Dowling-Meara (EBSDM). The patient had a C to T
      transition at the first position of codon 125, which resulted in Arg-->Cys at the
      N-terminus of the rod domain in the keratin K14 gene. The mutation position
      described here was identical to those reported in some other EBSDM patients. Our
      result revealed mutation in the peptide initiating helical structure of keratin
      K14 and, together with the results of other workers, suggests that the mutation
      in the keratin K14 gene of EBSDM sufferers occurs in virtually every ethnic group
      and geographical area.

PMID- 8867770
TI  - Failure to detect paramyxovirus RNA in the skin of connective tissue disease.
AB  - Etiology of connective tissue disease is unknown. The association of infectious
      agents has been suspected serologically, ultrastructurally and recently by means
      of molecular biological techniques. We extracted RNA from lesions of 25 discoid
      lupus erythematosus, 9 systemic LE, and 3 systemic sclerosis biopsies, and
      reverse transcription-polymerase chain reaction was performed for all
      paramyxoviruses known to infect human beings. None of the samples yielded
      positive signal for any of the viruses. The existence of paramyxovirus in the
      skin of connective tissue disease is very unlikely.

PMID- 8867771
TI  - Studies on transient graft-versus-host disease in BALB/c nude mice injected with
      allogeneic C57BL/6 splenocytes.
AB  - Graft-versus-host disease (GVHD) is known to cause profound dysregulation of the
      immune system, although its effector mechanisms are not fully understood. In this
      study, we investigated what factors influenced the development of GVHD. BALB/c
      nude mice (H-2d) injected with MHC-disparate B6(H-2b) spleen cells exhibited
      transient GVHD such as hunched back, diarrhea, loss of body weight and
      splenomegaly. No animals died during the period of observation. BALB/c nude mice
      produced alloantibodies to the donor cells. The injection of the serum from GVHD
      nude mice into naive nude mice can protect from GVHD. Donor derived H-2b+ cells
      were recognized in the recipient lymph nodes and skin. Prevention of GVHD was
      achieved by the pretreatment of spleen cells with anti-Thy-1.2 antibody or anti
      CD4 antibody and complement, while it was not done by the pretreatment of spleen
      cells with anti-CD8 antibody and complement. These data demonstrate that Thy-1.2+
      CD4+ CD8- lymphocytes are important effector cells and alloantibodies to the
      donor cells prevent GVHD in this model.

PMID- 8867772
TI  - Ankle to arm index response to exercise and heat stress in healthy subjects.
AB  - Ankle to arm index (AAI) defined as the ratio of ankle systolic blood pressure
      (ASBP), to brachial systolic blood pressure is largely used in the study of lower
      extremity arterial disease (LEAD). To study the hypothesis of the shunt of blood
      away from the skin as the explanation of AAI decrease in exercise, we studied the
      AAI and ASBP responses to an increase in cardiac output originating from an
      increase either in muscle blood flow (exercise) or in cutaneous blood flow
      (thermal stress). Brachial systolic pressure, ankle systolic pressure and heart
      rate (HR) were measured in 9 healthy subjects at rest, during heart thermal
      stress and following maximal exercise on a cycle ergometer. Compared to resting
      values, AAI decreased in all subjects from 1.05 +/- 0.07 to 0.75 +/- 0.07 (P <
      0.05) 1 min following exercise and from 1.08 +/- 0.07 to 0.94 +/- 0.05 (P < 0.05)
      during heat stress. On the other hand, HR increased from 72.8 +/- 12.2 to 112.4
      +/- 19.6 (P < 0.05) min following exercise and from 75.5 +/- 13.6 to 96.8 +/-
      15.3 (P < 0.05) during heat stress. Since a comparable relation exists between
      AAI and HR in thermal stress and exercise, we suggest that the decrease in AAI in
      normal subjects following exercise is due to turbulences at high flow levels,
      rather than the shunting of blood to active muscles in exercise.

PMID- 8867773
TI  - No differential effects of porcine and human insulin on muscle sympathetic nerve
      activity during euglycaemia or hypoglycaemia.
AB  - On the basis of some clinical studies in diabetic patients, and experimental
      studies in normal humans, it has been suggested that hypoglycaemic autonomic
      responses are augmented with porcine (PI) compared to human insulin (HI). A
      difference in sensory processing has been reported following insulin-induced
      hypoglycaemia with PI compared to HI, and has been interpreted as different
      insulin effects on the central nervous system. In a double blind crossover
      comparison of HI and PI in nine healthy subjects, microneurographic recordings of
      muscle sympathetic nerve activity (MSNA) were performed, as well as measurements
      of cardiovascular and hormonal responses during a low dose hyperinsulinaemic
      euglycaemic glucose clamp (plasma insulin 60.1 +/- 1.9 mU ml-1 (mean +/- SEM)),
      followed by a period of insulin-induced hypoglycaemia. Plasma insulin and glucose
      were identical in the two sessions. Plasma glucose nadir during hypoglycaemia was
      2.4 +/- 0.2 mmol l-1 for HI and 2.5 +/- 0.1 mmol l-1 for PI. During euglycaemia,
      MSNA increased from 24 +/- 2 to 34 +/- 3 and 23 +/- 2 to 30 +/- 2 burst/min
      (P:NS) for HI and PI, respectively, and during hypoglycaemia to 49 +/- 4 and 45
      +/- 2 bursts min-1 (P:NS), respectively. The maximal hypoglycaemic increments of
      MSNA were not different (HI 15 +/- 4; PI 15 +/- 2 bursts min-1 (P:NS)) Responses
      of plasma noradrenaline and haemodynamic parameters did not differ either. This
      study does not indicate differing sympathetic responses to PI and HI in healthy
      humans. Evidence for a modulating effect of insulin on central sympathetic
      outflow was not found.

PMID- 8867774
TI  - Static-charge-sensitive bed ballistocardiography in cardiovascular monitoring.
AB  - We evaluated the autonomic influence on balistocardiograms recorded by a static
      charge-sensitive bed for cardiovascular monitoring in nine healthy males (20-44
      years) and its clinical use in 11 patients who underwent coronary bypass surgery
      (51-59 years). The ballistocardiogram displayed a distorted low amplitude from
      the empty beating heart during bypass surgery, impaired by a reduced effective
      transmural filling pressure of the heart, and returned to its pre-bypass level
      when the preload to the heart and its pumping was restored. Submaximal dynamic
      exercise and isoprenaline caused the heart rate to rise to 90-114 beats min-1,
      and increased the ballistocardiographic amplitude threefold, while at the same
      time shortening the interval between the R-wave of the electrocardiogram and the
      peak of the ballistocardiographic waveform (P < 0.01). In contrast, atropine
      accelerated the heart rate to 96 beats min-1, but did not significantly change
      the amplitude or temporal pattern of the ballistocardiogram. Thus, the
      ballistocardiogram reflects sympathetic and parasympathetic influence on the
      contractility of the myocardium and the effect of cardiac filling (e.g. during
      bypass surgery).

PMID- 8867775
TI  - Transperitoneal transport of sodium during hypertonic peritoneal dialysis.
AB  - The mechanisms of transperitoneal sodium transport during hypertonic peritoneal
      dialysis were evaluated by kinetic modelling. A total of six nested mathematical
      models were designed to elucidate the presence or absence of diffusive, non
      lymphatic convective and lymphatic convective solute transport. Experimental
      results were obtained from 26 non-diabetic patients undergoing peritoneal
      dialysis. The model validation procedure demonstrated that only diffusive and non
      lymphatic convective transport mechanisms were identifiable in the
      transperitoneal transport of sodium. Non-lymphatic convective sodium transport
      was the most important quantitative transport mechanism during the first 90 min
      of the dwell. Significant sodium sieving was demonstrated and explains the
      observation of hypernatremia in dialysis with hypertonic dialysis fluid.

PMID- 8867776
TI  - Effective role of the renin-angiotensin system in the control of prostanoid
      synthesis and renal function in healthy women with moderate salt depletion.
AB  - The interaction between moderate salt depletion and urinary excretions of
      prostanoids (PGE2,6-keto-PGF1 alpha and TxB2), as well as the effective role of
      the activated renin-angiotensin system (RAS), in the control of renal function
      and urinary prostanoid excretions have been investigated in healthy women. Salt
      depletion (SD, n = 8) was induced by low sodium chloride dietary intake (< or =
      60 mmol per day) and combined treatment with natriuretic and potassium sparing
      drugs. The cumulative sodium deficit was 381 +/- 55 mmol. The renal function and
      urinary excretion of prostanoids were evaluated during hypotonic polyuria (oral
      water load) and subsequent moderate antidiuresis (lysine-8-vasopressin (LVP) low
      dose infusion). Basal plasma renin activity (PRA) and urinary aldosterone
      excretion were determined, before the water load, in both the SD group and
      control studies in normal balance of sodium and potassium (N, n = 20). Paired
      studies were performed in the absence and in the presence of enalapril in the
      same SD group, as well as in a subgroup, with normal sodium and potassium
      balance, previously studied (N3, n = 6). In the SD vs. N group, significantly
      higher values of PRA and urinary aldosterone excretion were found. The renal
      antinatriuretic mechanism was activated and the diuretic response to water load
      depressed. During polyuria, the urinary 6-keto-PGF1 alpha and TxB2 excretions
      were significantly higher, probably reflecting an increase in the renal synthesis
      of their precursors. During the late LVP infusion, the urinary PGE2 excretion was
      also significantly increased, in absence of significant differences in urinary
      flow rate. In both SD and N3 groups, enalapril decreased the mean arterial
      pressure (MAP). Despite the decrease in MAP, not significantly different in SD
      vs. N3 group, the drug did not significantly affect the creatinine clearance.
      Also, the urinary prostanoid excretions were not significantly affected by
      enalapril. However, in the SD group, but not in the N3 group, the drug was
      effective in significantly decreasing the absolute and fractional excretions of
      sodium and chloride. Moreover, the plasma potassium concentration significantly
      decreased, despite the concurrent decrease in urinary potassium excretion. The
      data suggest that: (1) in salt depletion, the prostanoid release from the renal
      cortical structures was stimulated; (2) the renal prostanoid synthesis, either
      activated (sodium depletion) or not (normal sodium and potassium balance), was
      not affected by the RAS pharmacological blockade in the short-term; (3) in salt
      depletion, the RAS blockade recruited a homeostatic mechanism responsible for the
      improved renal salt conservation, as well as for the redistribution of potassium
      between the extra- and intra-cellular compartments.

PMID- 8867777
TI  - Influence of external pressure on transcutaneous oxygen tension and laser Doppler
      flowmetry on sacral skin.
AB  - The effects of external pressure upon transcutaneous oxygen tension (tcpO2) and
      skin blood flow (SKBF) over the sacral area were studied in 16 healthy
      volunteers. Pressure was applied on the sacral area using a special device which
      included tcpO2 and laser-Doppler flowmetry probes. The mean values of tcpO2, SKBF
      and wave occurrence of the flow were analysed for 18 increasing pressure levels.
      A significant decrease of tcpO2 was observed from 40 mmHg (5.3 Kpa) of applied
      pressure, while we obtained a significant decrease of SKBF when the external
      pressure was at 20 mmHg (2.7 Kpa). Using a non-linear regression model, we have
      found a fourth degree polynomial to describe the relationship between tcpO2 and
      SKBF according to increasing pressure. SKBF slow wave occurrence decreased when
      external pressure was at 10 mmHg (1.3 Kpa), while rapid wave occurrence
      significantly decreased only at 120 mmHg (16.1 kPa) pressure.

PMID- 8867778
TI  - Different levels of sensory neuropeptides (calcitonin gene-related peptide and
      substance P) during and after exercise in man.
AB  - The aim of this study was to investigate the regulation of two sensory peptides
      calcitonin gene-related peptide (CGRP) and substance P, reflected as circulating
      levels during provocation of the sympathetic nervous system. Levels in
      hypertensives, diabetics (NIDDM) and controls were assayed before, during and
      after an exercise test (average work load carried out was 76 +/- 10 kJ). CGRP
      levels increased progressively during exercise (P < 0.001), with maximum level at
      maximum exercise. This was significant in all three groups; hypertensives P <
      0.001, diabetics P < 0.01 and controls P < 0.001. No differences in circulating
      revels of CGRP between the three groups were found. Substance P levels were
      fairly constant during exercise but increased 30 min after exercise (P < 0.01) in
      the total group. We hypothesize that CGRP might provide a counter-regulatory
      mechanism to the sympathetic vasoconstrictor transmitters noradrenaline (NA) and
      neuropeptide Y (NPY) during sympathetic activation. Substance P did not increase
      during exercise. This suggests differential regulation and function of the two
      vasodilatory peptides.

PMID- 8867779
TI  - A simple, non-invasive and inexpensive method for evaluating the displacement of
      local tissue surfaces: from vascular changes to muscle contraction.
AB  - This paper describes a non-invasive, very inexpensive method of estimating tissue
      displacements of various origin that is easy and fast to set up. This technique
      utilizes an inductive proximity sensor (IPS), which is a non-contact length
      transducer measuring the distance between its probe and a metal target. Its
      working principle is based on the electromagnetic coupling originating between
      the sensor probe, a source of high-frequency magnetic field, and the metal target
      where parasitic currents take place. The linear working range of the IPS model
      used here is 0.1 to 6 mm probe-target distance, its resolution is about 2
      microns. The IPS has been employed on rabbits and humans to measure the
      displacement of a target glued to the skin of various body areas with respect to
      the fixed probe of the sensor. Its high resolution, together with an extensive
      working range, allows the evaluation of numerous physiological events which
      produce displacements ranging from 2 microns -- to 9 mm, reflecting either tissue
      volume changes or movements. In particular, an interesting application is to
      monitor, through volume variations, the extent and the time course of local
      vascular modifications induced by manoeuvres which elicit changes in vasomotor
      tone; vascular filling, tissue swelling etc. Therefore, this measure may be
      considered a 'surface plethysmography' record. In addition, the contractions of
      skeletal muscles, under either isotonic or isometric conditions, can be estimated
      through this sensor. This system may therefore find applications for research
      purposes and practical demonstrations to students.

PMID- 8867780
TI  - Temporal and spatial distributions of yeast nucleoside diphosphate kinase
      activities and its association with the Cdc8p.
AB  - Nucleoside diphosphate kinase (E.C. 2.7.4.6.) is a broad substrate-specific
      enzyme that catalyzes the phosphorylation of nucleoside diphosphates to the
      corresponding triphosphates in nucleic acid biosynthesis. In this report, we
      investigate its spatial and temporal distributions in yeast to understand how the
      enzyme exerts its gene function(s). Our results show that the enzyme is
      predominantly cytoplasmic. A substantial amount of enzyme activity (40-50%) may
      be associated with the cell membrane. Less than 1% of total activity was detected
      in the nuclear fraction. Approximately 3% was found in the mitochondrial
      fraction. When yeast cultures were synchronized, we found that Saccharomyces
      cerevisiae nucleoside diphosphate kinase did not show cell cycle periodicity, as
      Schizosaccharomyces pombe enzyme did. To explore its link with DNA synthesis, we
      investigated its relationship with the Cdc8p (dTMP kinase). We demonstrated a
      physical interaction between these proteins in vitro, as evidenced that the
      GST:Cdc8p protein affinity column could retain a subpopulation of nucleoside
      diphosphate kinase activity from yeast crude extract. Furthermore, when GST:Cdc8p
      protein was expressed in yeast, the protein could bind to the glutathione
      agarose, along with nucleoside diphosphate kinase, suggesting that there is an
      interaction between GST:Cdc8p and nucleoside diphosphate kinase in vivo. Our
      results provide evidence for at least a two-enzyme complex that may well
      facilitate nucleotide channeling in the cell.

PMID- 8867781
TI  - Magnesium and cardiovascular biology: an important link between cardiovascular
      risk factors and atherogenesis.
AB  - In this review, a rationale is presented for how hypercholesterolemia,
      hypertension, diabetes mellitus, end-stage renal disease, renal dialysis, and
      prolonged stress can all lead to atherosclerosis, ischemic heart disease, and
      stroke. The data indicate that Mg deficiency caused either by poor diet and/or
      errors in Mg metabolism may be a missing link between diverse cardiovascular risk
      factors and atherosclerosis. Data from our laboratories and others indicate that
      reduction in extracellular and intracellular free Mg ions (Mg2+) can induce an
      entire array of pathophysiological phenomena known to be important in
      atherogenesis, that is, vasospasm, increased vascular reactivity, elevation in
      [Ca2+]i, formation of proinflammatory agents, oxygen radicals, platelet
      aggegation, reduction in cardiac bioenergetics, cardiac failure, oxidation of
      lipoproteins, gender-related modulation of endothelial-derived relaxing
      factor/NO, changes in membrane fatty acid saturation, changes in membrane
      plasmalogens and N-phospholipids (suggesting changes in intracellular
      phospholipid signals), and probably transcription factors.

PMID- 8867782
TI  - L-tryptophan induces expression of collagenase gene in human fibroblasts:
      demonstration of enhanced AP-1 binding and AP-1 binding site-driven promoter
      activity.
AB  - Collagenase, a prototypic matrix metalloproteinase, plays a major role in the
      degradation of the extracellular matrix. The essential amino acid L-tryptophan
      was recently shown to stimulate the expression of collagenase gene in human
      dermal fibroblast cultures. In this study, we focused our attention on the
      mechanisms responsible for activation of collagenase transcription by L
      tryptophan. Incubation of fibroblasts with L-tryptophan resulted in a dose- and
      time-dependent elevation of collagenase and tissue inhibitor of metalloproteinase
      mRNA levels. The maximum enhancement in collagenae mRNA was approximately 50
      fold. This effect was not abolished by cycloheximide, suggesting independence
      from ongoing protein synthesis. Transient cell transfections with a
      promoter/reporter gene construct containing 3.8 kb of 5' flanking DNA of the
      human collagenase gene linked to the chloramphenicol acetyl transferase (CAT)
      gene or a construct containing three phorbol ester-responsive AP-1 binding
      sequences (12-O-tetradecanoyl-phorbol-13-acetate-responsive element) in front of
      the thymidine kinase promoter linked to the CAT gene indicated enhancement of
      promoter activity by L-tryptophan. Furthermore, electrophoretic DNA mobility
      shift assays demonstrated enhanced DNA-protein complex formation specific for an
      AP-1 binding site probe with nuclear extracts prepared from cells incubated with
      L-tryptophan. These results collectively suggest that activation of collagenase
      gene expression in dermal fibroblasts by L-tryptophan is mediated through AP-1
      binding elements in the collagenase gene promoter that are sufficient for gene
      response.

PMID- 8867783
TI  - Subcellular distribution of soluble and membrane-bound Arg-beta-naphthylamide
      hydrolyzing activities in the developing and aged rat brain.
AB  - The subcellular distribution of soluble and membrane-bound Arg-beta-naphthylamide
      hydrolyzing activities was studied in the left and right rat brain during
      development and aging. During development, the soluble activity was
      heterogeneous, whereas adult animals showed the highest activity in the
      synaptosomal fraction. However, except in fetuses, membrane-bound activity was
      greatest in the microsomal fraction. Except in microsomal and myelin fractions,
      soluble and membrane-bound activities showed a decrease in 1-wk-old rats compared
      with fetuses and a subsequent increase to adult levels in 1-mo-old rats. This
      profile differed in the microsomal fraction, which increased steadily throughout
      development. In the synaptosomal fraction, both activities were lower in 24-mo
      old rats than in 5-mo-old animals. No differences between the hemispheres were
      observed in soluble or membrane-bound fractions at any age tested.

PMID- 8867784
TI  - Tax-independent stimulation of human T-cell leukemia virus type-I expression and
      differential effects on its infectivity by subtoxic and toxic doses of 3
      methylcholanthrene.
AB  - Using the human T-cell leukemia virus type I (HTLV-I) infected SLB-I T-cell line,
      we showed in this study that 5-d treatment with the maximal subtoxic 3
      methylcholanthrene (3-MC) dose (0.25 microgram/ml), as well as with a 3-MC dose
      that inhibits 50% of the cell growth (5 micrograms/ml), profoundly increased the
      level of viral RNA. Exposure to these 3-MC doses for 5 d before transient
      transfection of HTLV-I LTR-CAT construct into these cells markedly stimulated CAT
      activity, indicating that 3-MC exerted its effect by a trans-acting mechanism. A
      similar stimulation was observed when this construct was transfected into 3-MC
      treated uninfected Jurkat cells, indicating that this trans-acting effect was
      independent of the viral tax protein. However, although the subtoxic 3-MC dose
      increased also the capacity of SLB-I cells to transmit the virus to normal
      peripheral blood lymphocytes in coculture, the toxic dose strongly reduced this
      capacity. No inhibition by this toxic dose was observed in the viral protein
      synthesis or processing nor in the final release of the virus from the cells.
      However, the virions released under the influence of this 3-MC dose were found to
      contain mainly the uncleaved gag precursor polypeptide and a low level of reverse
      transcriptase. Thus, the reduced virus transmission capacity of the host cells
      can be ascribed to this structural defect, which presumably lowered the viral
      infectivity.

PMID- 8867785
TI  - Nutritional influences on in vitro splenic lymphocyte proliferation in Psammomys
      obesus (Rodentia Gerbillidae).
AB  - The standard laboratory diet administered to sand rat (Psammomys obesus) induces
      the following physiological and immunological changes: hyperglycemia and
      hypercholesterolemia involving mainly the free fraction of cholesterol, with an
      elevation of high-density-lipoprotein levels and a decrease in B and T splenic
      lymphocyte proliferation in the presence of different mitogens PHA-P, Con A and
      LPS. These results demonstrate the important modification that could be induced
      in sand rat by the standard laboratory diet as compared with natural diet, and
      thus the sand rat (P. obesus) appears to be an interesting model for studies on
      experimental diabetes mellitus.

PMID- 8867786
TI  - Melatonin immunoreactivity in the photosynthetic prokaryote Rhodospirillum
      rubrum: implications for an ancient antioxidant system.
AB  - Rhodospirillum rubrum is a spiral anoxygenic photosynthetic bacterium that can
      exist under either aerobic or anaerobic conditions. The organism thrives in the
      presence of light or complete darkness and represents one of the oldest species
      of living organisms, possibly 2-3.5 billion years old. The success of this
      prokaryotic species may be attributed to the evolution of certain indole
      compounds that offer protection against life-threatening oxygen radicals produced
      by an evolutionary harsh environment. Melatonin, N-acetyl-5-methoxytryptamine, is
      an indolic highly conserved molecule that exists in protists, plants, and
      animals. This study was undertaken to determine the presence of an immunoreactive
      melatonin in the kingdom Monera and particularly in the photosynthetic bacterium,
      R. rubrum, under conditions of prolonged darkness or prolonged light.
      Immunoreactive melatonin was measured during both the extended day and extended
      night. Significantly more melatonin was observed during the scotophase than the
      photophase. This study marks the first demonstration of melatonin in a bacterium.
      The high level of melatonin observed in bacteria may provide on-site protection
      of bacterial DNA against free radical attack.

PMID- 8867787
TI  - Interaction of BiP with substance P and nucleotides.
AB  - A rapid and simple spin column assay has been used to study interactions of BiP
      with substance P (SP) and ATP. At 4 degrees C, the binding of SP to BiP requires
      ATP and a stable SP-BiP.ATP complex is formed. Nonhydrolyzable ATP analogues or
      ADP cannot replace ATP. Although ATP converts BiP dimers to monomers, the
      requirement for ATP for SP binding is not solely due to BiP dissociation, because
      purified BiP monomers also require ATP for peptide binding. At 37 degrees C,
      there is rapid binding of SP to BiP even in the absence of ATP and, in fact, ATP
      at concentrations above 5 microM causes release of SP from BiP. At this higher
      temperature, there is also rapid hydrolysis of ATP bound to BiP. These results
      extend our previous results (Brot et al., 1994) that indicated the formation, at
      low ATP concentrations, of a labile SP.BiP.ATP complex that, after ATP
      hydrolysis, resulted in a stable SP.BiP.ADP complex.

PMID- 8867788
TI  - Cell surface accumulation of overexpressed hamster lysosomal membrane
      glycoproteins.
AB  - We cloned and sequenced cDNAs encoding two lysosomal membrane glycoproteins, lgp
      A and lgp-B, from Chinese hamster ovary cells. The deduced amino acid sequences
      of these proteins are similar to those of the other known members of this
      conserved family (also known as "LAMP" proteins). We used the cDNAs to generate
      stable lines of hamster lgp-expressing mouse NIH-3T3 cells, rat NRK cells, and
      monkey CV-1 cells. We also generated hybridomas that secrete antibodies specific
      for hamster lgp-A and lgp-B, enabling us to distinguish foreign from endogenous
      lgps in a wider variety of transfected cell lines. One line of mouse NIH-3T3
      cells that expresses hamster lgp-B was studied in detail. Whereas most of the
      hamster lgp-B appeared to be transported to lysosomes in these cells, butyrate
      induced overexpression resulted in the accumulation of a significant proportion
      of the total on the plasma membrane. In addition, overexpression of this foreign
      lgp-B also resulted in the appearance of the endogenous mouse lgp-A and lgp-B on
      the plasma membrane. Characterization of this accumulation suggested that it
      resulted from competition for one or more limited components in the transport
      pathway(s) to lysosomes. Endocytosis from the plasma membrane appeared to be one
      step that was saturable.

PMID- 8867789
TI  - Androgenic regulation of protein kinase CK1 in the prostatic cell.
AB  - We examined the androgenic regulation of protein kinase CK1 in rat ventral
      prostate cytosolic and chromatin fractions. On androgen deprivation, CK1 in both
      the nuclear and cytoplasmic compartments decreases slowly at a similar rate.
      Stimulation of regrowth in the prostate does not evoke an early differential
      modulation in the CK1 because it increased in both the cytosol and chromatin only
      by 24 h after androgenic stimulus. These changes in CK1 relate to its proposed
      role in cell regulation at mitosis and differ from those in protein kinase CK2
      that demonstrates rapid modulations in the nuclear compartment under similar
      conditions.

PMID- 8867790
TI  - Serine acetyltransferase from Arabidopsis thaliana can functionally complement
      the cysteine requirement of a cysE mutant strain of Escherichia coli.
AB  - Serine acetyltransferase, a key enzyme in the L-cysteine biosynthetic pathway of
      sulfate assimilating organisms, catalyzes the formation of O-acetylserine, the
      immediate precursor of L-cysteine. In higher plants, it is thought that sulfur
      assimilation occurs primarily in leaf chloroplasts; however, serine
      acetyltransferase is not localized exclusively in this tissue and organelle. At
      least three genes for serine acetyltransferase have been identified in the higher
      plant Arabidopsis thaliana. Reported here is a cDNA corresponding to one of these
      genes, SAT1, a 1,079 bp clone with an open reading frame predicted to encode a 34
      kDa protein that is able to functionally complement a serine acetyltransferase
      mutant strain of Escherichia coli. The predicted amino acid sequence of SAT1
      shows significant homology with bacterial serine acetyltransferases. SAT1,
      expressed as a recombinant protein, shows serine acetyltransferase enzyme
      activity and cross-reacts with an antibody against the homologous E. coli enzyme.
      The first 40 amino acids of the SAT1 polypeptide resembles a plastid transit
      peptide, but the polypeptide is probably not plastid localized. Genomic DNA blot
      analysis of A. thaliana showed that SAT1 is a single copy gene and RNA blot
      analysis revealed that SAT1 is expressed in both leaves and roots.

PMID- 8867791
TI  - Possible involvement of the mouse Grg protein in transcription.
AB  - The mouse Grg gene encodes a 197 amino acid nuclear protein homologous to the
      amino-terminal domain of the product of the groucho (gro) gene of the Drosophila
      Enhancer of split complex. Recent work has suggested that the gro protein
      functions as a transcriptional corepressor during Drosophila development. We
      therefore examined possible roles of the mouse Grg protein in DNA binding and in
      vitro transcription. No sequence-specific DNA binding activity was detected by
      polymerase chain reaction-DNA binding site selection nor was the glutamine-rich
      Grg protein capable of acting as an activation domain in an in vivo
      transactivation assay. However, depletion of Grg protein from HeLa nuclear
      extracts inhibited the in vitro transcription activity of the extracts. We
      suggest that Grg protein may interact with components of the basal transcription
      machinery.

PMID- 8867792
TI  - Ultraviolet light and serum induce similar delayed responses that lead to
      activation of a mitogen-responsive promoter.
AB  - The transferrin receptor promoter is responsive to growth factors and mitogens.
      This induction is a delayed response and does not occur until several hours after
      stimulation of quiescent cells by mitogens. The results described here show that
      the transferrin receptor promoter is also activated by treatment with ultraviolet
      (UV) light. Activation of the promoter by UV light is dose dependent and requires
      the same cis-acting elements that are activated in response to serum and other
      mitogens. As with serum stimulation, activation of the promoter by UV light is a
      delayed event and is not initiated until 6 h after treatment. This coincides with
      the induction of nuclear factors that bind with specificity to the required cis
      acting elements. A major GC-box binding factor induced by UV light is also
      induced by serum and has been shown to be supershifted by antibodies to the Sp1
      transcription factor.

PMID- 8867793
TI  - Molecular cloning of two rat Na+/Pi cotransporters: evidence for differential
      tissue expression of transcripts.
AB  - Recently, Na+/Pi cotransport activity has been demonstrated in rat liver
      hepatocytes. Here, we report the isolation of two Na+/Pi cotransporter cDNAs
      (RNaPi-1a and RNaPi-1b) from a rat liver cDNA library. The two cDNAs have the
      same coding but different 5'-untranslated regions. The rat cDNAs encode a
      polypeptide of 465 amino acids, having 62% and 66% identity with the rabbit NaPi
      1 and human kidney Na+/Pi cotransporter, respectively. Northern blot analysis
      showed that a RNaPi-1a--specific probe detected two major transcripts (2.3 and
      1.8 kb), whereas a RNaPi-1b--specific probe hybridized with one transcript (1.8
      kb) in rat kidney, liver, and hepatocytes in primary culture. Rat liver expressed
      much higher levels of RNaPi-1a than RNaPi-1b, whereas the converse was true for
      rat kidney. Low levels of RNaPi-1 mRNAs were also detected in rat heart, brain,
      and skeletal muscle. These findings indicate that there are at least two isoforms
      of RNaPi-1 transcripts expressed in liver and kidney and that the levels of
      expression of the RNaPi-1a and RNaPi-1b may be controlled by tissue-specific
      factors.

PMID- 8867794
TI  - Bacterial aspartate kinase-like activity in human platelet.
AB  - One form of a group of enzymes known as aspartate kinases, primarily reported in
      prokaryotes and plants, might also exist in animal cells. Here we report the
      immunodetection of an aspartate kinase-like activity in human platelets using
      antibodies against the pure form of the enzyme purified from Escherichia coli.
      Moreover, the enrichment of platelet extracts with the bacterial kinase results
      in the phosphorylation of discrete forms mainly of membrane-bound endogenous
      polypeptides.

PMID- 8867795
TI  - Hyaluronan mediates sperm motility by enhancing phosphorylation of proteins
      including hyaluronan binding protein.
AB  - The present study was carried out to explore the mechanisms underlying hyaluronan
      induced sperm motility. We demonstrate for the first time the enhanced cellular
      protein phosphorylation in hyaluronic acid stimulated cauda spermatozoa. Labeling
      of spermatozoa with [Pi] orthophosphoric acid yielded a wide range of labeled
      phosphoproteins in presence of hyaluronan. Under these experimental conditions,
      we further show tyrosine specific phosphorylation of proteins. In addition, this
      is also the first report showing enhanced phosphorylation of 34 kDa hyaluronan
      binding protein in response to hyaluronan. The role of 34 kDa hyaluronan binding
      protein in hyaluronan-induced spermatozoa is supported by elevated production of
      inositol triphosphate accompanied by increased phosphorylation in Triton X-100
      insoluble cytoskeletal proteins. The evidence strongly suggests the biological
      importance of hyaluronan binding protein phosphorylation in the transduction of
      signals resulting from the interaction of hyaluronate with the sperm surface.

PMID- 8867796
TI  - Bibliography of cellular and molecular biology research.

PMID- 8867797
TI  - Computer survey for likely genes in the one megabase contiguous genomic sequence
      data of Synechocystis sp. strain PCC6803.
AB  - Using the computer program GeneMark, the open reading frames (ORFs) previously
      assigned within the one megabase sequence data of the genome of the
      cyanobacterium, Synechocystis sp. strain PCC6803 (Kaneko et al., DNA Res. 2: 153
      166, 1995), were re-examined. Matrices required by GeneMark for its statistical
      calculation were generated and modified by running a script termed GeneMark
      Genesis that performed recursive application of GeneMark against the
      Synechocystis data and evaluated the probability scores for optimization. Based
      on the matrices thus generated, 752 of the 818 previously assigned ORFs (92%)
      were supported by GeneMark as likely coding sequences, of which 26 were predicted
      to start at more internal positions than previously assigned. In addition, 50
      ORFs were newly identified as likely coding sequences, most of them being shorter
      than 300 bp. Thus, the procedure was proven to be very powerful to locate likely
      coding regions within the genomic sequence data of Synechocystis without having
      prior information concerning their similarity to the genes of other organisms.
      However, GeneMark did not predict 66 previously assigned ORFs as likely genes: 14
      of them showed significant degrees of similarity to known genes and 10 others
      were found within IS-like elements. It seems that these genes, many of which
      appear to be exogenous origin, escaped detection by GeneMark as in the case of
      "class 3 (horizontally transferred) genes" of E. coli, which in turn suggests
      that genes of different phylogenetic origins might also be detected as such by
      modifying the matrices.

PMID- 8867798
TI  - Identification of the coding region of Saccharomyces cerevisiae chromosome VI
      using the computer program GenMark.
AB  - We searched the nucleotide sequence of budding yeast Saccharomyces cerevisiae
      chromosome VI (270 kb) for candidate coding regions, using the computer program
      GenMark. One hundred and twenty-nine putative genes were identified, which is
      almost the same as the number of ORFs on this chromosome. Nineteen new putative
      genes were identified through the GenMark analysis. Most large ORFs were also
      correctly identified (87% of the predicted putative genes identified by the
      GenMark (110 of 127) matched the reported ORFs). The new coding regions were
      mostly small but they were distinguished from the more than 2000 ORFs identified
      by Genetyx. GenMark did not predict 17 ORFs that were over 300 bp long. As these
      ORFs include known genes, their sequence context may differ somewhat from that of
      typical yeast genes. These analyses revealed the high potential of GenMark to
      identify putative genes from numerous short ORFs and will produce information on
      the likelihood of their being actual genes.

PMID- 8867799
TI  - Molecular analysis of a putative transposable retroelement from the Zea genus
      with internal clusters of tandem repeats.
AB  - The molecular characterization of a recently discovered family of long repetitive
      sequences, termed ZLRS, is described. These elements belong to the class of
      moderate dispersed repetitive DNA and are specific to the Zea genus. An 8089-bp
      sequence from a Zea diploperennis ZLRS element have been elucidated. Sequence
      analysis reveals the presence of a long terminal repeat-like region, two clusters
      of different tandem repeats and several ORFs. On these grounds, ZLRS could be
      considered a new member of the superfamily of transposable retroelements. Tandems
      are present in the majority of ZLRS elements, they show an important stem-loop
      secondary structure predicted by the computer and their sequence conservation
      suggests a functional role.

PMID- 8867800
TI  - Reproducible alterations of DNA methylation at a specific population of CpG
      islands during blast formation of peripheral blood lymphocytes.
AB  - We investigated the changes in the methylation patterns of CpG islands associated
      with blast formation of human peripheral blood lymphocytes activated by anti-CD3
      and interleukin-2 (IL-2), using restriction landmark genomic scanning with a
      methylation-sensitive restriction enzyme (RLGS-M) system. Of about 2,100 NotI
      spot/loci which were analyzed, only 10 showed changes, whereas drastic changes
      have been observed in cases of malignant and SV40 transformation. These changes
      were highly reproducible for samples from both the same and different
      individuals. Even the timing of the changes after cultivation was the same. Thus,
      we concluded that at least the genomic DNA methylation state in vivo was
      essentially retained in T blast cells activated in vitro by induction with IL-2
      and anti-CD3, which are commonly used in biological experiments as well as
      clinical diagnosis and therapy.

PMID- 8867801
TI  - Isolation of human purH gene expressed in the rodent transformant cells by
      subtractive enrichment of 3'-untranslated region of human transcript.
AB  - A subtraction procedure was developed for identification and isolation of a human
      gene transcribed in mouse transformant cells. The procedure was based on
      subtractive enrichment of the products that were amplified by the combination of
      reverse transcription and polymerase chain reaction from the 3'-untranslated
      region (3'-UTR) of human poly(A)+ RNA expressed in the mouse transformant cells.
      To assess the ability and usefulness of the procedure, we attempted to recover
      the human purH gene from a mouse transformant cell line, which was originally
      established by functional complementation using the human metaphase chromosome
      mediated gene transfer technique from a mouse purH-negative mutant cell line.
      Using our procedure, a part of the human transcript in the transformant cells was
      successfully identified and isolated. The full-length cDNA was isolated using the
      3'-UTR clone as a probe, and its biological activity was confirmed by introducing
      it into the mouse purH-negative mutant cells.

PMID- 8867802
TI  - Improved large-scale preparation of phage T4 endonuclease VII overexpressed in E.
      coli.
AB  - Using PCR, we cloned T4 gene 49, which encodes the endonuclease VII, and the
      inactive mutant gene 49 amE727 into vector pET-11a. In combination with
      Escherichia coli host strain BL21 (DE3), this system provided excellent
      repression of the expression of the highly toxic protein before induction with
      IPTG. After induction, the proteins were made in high quantities while remaining
      soluble. Dilution of the crude lysate at 1:10,000 continued to show a highly
      specific activity in the case of the wild-type enzyme. The protein was purified
      to homogeneity with a recovery of 33% using two chromatography steps. The yield
      was 20 times higher and the specific activity 500 times higher than that obtained
      by using the previously published protocol.

PMID- 8867803
TI  - A new approach to determine the effect of mismatches on kinetic parameters in DNA
      hybridization using an optical biosensor.
AB  - We have demonstrated a simple yet direct method for determining the kinetic
      parameters in DNA-DNA interactions using biosensor technology based on the
      surface plasmon resonance phenomenon; a technique that does not require complex
      DNA labeling. To determine the effect of mismatches on the kinetics involved in
      DNA-DNA interactions, DNA hybridization kinetics were monitored in real time
      using synthetic oligonucleotides less than 20 bases in length which contained
      either a complementary sequence or mismatched bases. Upon analysis of the kinetic
      parameters obtained in oligonucleotide hybridization, we found that they were
      significantly affected by the presence of mismatches as well as by their number
      and location in a DNA duplex. In addition, the presented biosensor method is
      sensitive enough to detect kinetic effects caused by the presence of a single
      mismatched base pair. Our findings strongly suggest that analysis of kinetic
      parameters involved in DNA-DNA interactions is advantageous for detecting the
      presence of mismatch base pairs in a DNA duplex.

PMID- 8867804
TI  - Cloning and sequencing of a 23-kb region of the Bacillus subtilis genome between
      the iol and hut operons.
AB  - Within the framework of an international project for the sequencing of the entire
      Bacillus subtilis genome, a 23-kb chromosomal segment, which covers the region
      between the iol and hut operons, has been cloned and sequenced, creating a 99-kb
      contig from the gnt operon to the wapA locus. This region (23351 bp) contains 25
      complete open reading frames (ORFs; genes) including deoR, dra, nupC and pdp and
      two partial ones. The region (5140 bp) containing these four genes, being also
      sequenced by H. H. Saxild et al., was sequenced by subjecting a long polymerase
      chain reaction product to random sequencing using phage M13mp19. However, we
      could detect no conflict, between two independently determined sequences, which
      could be attributed to our sequencing method. A homology search for the 24 newly
      identified gene products revealed significant homology to known proteins in 14 of
      them. It was notable that three proteins, encoded by the successive genes
      (yxeMNO), exhibited meaningful homology to the E. coli GlnHPQ products
      constituting a periplasmic ATP-dependent transport system for glutamine.

PMID- 8867805
TI  - Dynamic remodeling of nuclear architecture during the cell cycle.
AB  - The nuclear matrix is an integral part of nuclear structure which undergoes a
      profound reorganization during the cell cycle reflecting major changes in
      functional requirements. This includes the processes of DNA replication and gene
      expression at interphase and partitioning of the nuclear contents during mitosis.
      Using a monoclonal antibody (mAb2A) which specifically stains a novel nuclear
      meshwork which reorganizes during the cell cycle in Drosophila, we have initiated
      a study to: 1) more closely analyze this structural reorganization; 2) clone and
      characterize the antigens recognized by this antibody; and 3) isolate other
      interacting proteins in order to gain insight into the regulation of this
      process. The mAb2A-labeled structure changes from what appears as a diffuse
      meshwork at interphase to a distinct spindle-like scaffold at prophase. Since at
      metaphase the microtubules of the mitotic apparatus co-localize with the mAb2A
      spindle structure, a model is considered whereby the nuclear mAb2A-labeled
      scaffolding reorganizes during the cell cycle to provide a guide for the
      establishment of the mitotic apparatus. The mAb2A has identified two separate
      antigens, each of which shows similar distribution patterns. One of these
      antigens has been partially cloned and contains an unusual tandem ser-thr kinase
      domain. The association of this kinase homologue with a nuclear scaffold which
      reorganizes during the cell cycle suggests that it may be involved in regulating
      changes in nuclear architecture during the cell cycle and/or in mediating the
      downstream consequences of such changes.

PMID- 8867806
TI  - Common structural features of replication origins in all life forms.
AB  - Origins of replication (ORIs) among prokaryotes, viruses, and multicellular
      organisms appear to possess simple tri-, tetra-, or higher dispersed repetitions
      of nucleotides, AT tracts, inverted repeats, one to four binding sites of an
      initiator protein, intrinsically curved DNA, DNase I-hypersensitive sites, a
      distinct pattern of DNA methylation, and binding sites for transcription factors.
      Eukaryotic ORIs are sequestered on the nuclear matrix; this attachment is
      supposed to facilitate execution of their activation/deactivation programs during
      development. Furthermore, ORIs fall into various classes with respect to their
      sequence complexity: those enriched in AT tracts, those with GA- and CT-rich
      tracts, a smaller class of GC-rich ORIs, and a major class composed of mixed
      motifs yet containing distinct AT and polypurine or GC stretches. Multimers of an
      initiator protein in prokaryotes and viruses that might have evolved into a
      multiprotein replication initiation complex in multicellular organisms bind to
      the core ORI, causing a structural distortion to the DNA which is transferred to
      the AT tract flanking the initiator protein site; single-stranded DNA-binding
      proteins then interact with the melted AT tract as well as with the DNA
      polymerase alpha-primase complex in animal viruses and mammalian cells, causing
      initiation in DNA replication. ORIs in mammalian cells seem to colocalize with
      matrix-attached regions and are proposed to become DNase I-hypersensitive during
      their activation.

PMID- 8867807
TI  - Iron decreases the nuclear but not the cytosolic content of the neurohormone
      melatonin in several tissues in chicks.
AB  - This paper describes the influence of iron on both nuclear and cytosolic
      melatonin contents in several tissues of chicks. The neurohormone melatonin was
      estimated by means of radioimmunoassay. Iron, administered as FeCl3, decreased
      the nuclear melatonin level in a variety of tissues, including brain, heart,
      lung, kidney, and erythrocytes (nucleated cells in chicks) but was not seen in
      either the liver or gut. All variations related with iron were seen in the
      nuclear fraction, while only in the pineal gland did the melatonin content of the
      cytosol change as a result of iron treatment. We also observed a day-night rhythm
      in the nuclear melatonin: high nuclear levels of melatonin at night and low
      levels during the light period. This is the first report of nuclear localization
      of melatonin in any avian cell.

PMID- 8867808
TI  - Identification of a vitamin D3 response element in the fibronectin gene that is
      bound by a vitamin D3 receptor homodimer.
AB  - Fibronectin (FN) is an important adhesive noncollagenous glycoprotein involved in
      maintenance of the extracellular matrix and cell adhesiveness, loss of which has
      been implicated in the metastatic potential of cells. Regulation of FN occurs at
      the transcriptional level by the active metabolite of vitamin D3, 1,25
      dihydroxyvitamin D3 (1,25-(OH)2D3). Transient transfection of homologous and
      heterologous promoter reporter constructs into ROS 17/2.8 (rat osteosarcoma), NIH
      3T3 (mouse fibroblast), and MCF-7 (human mammary carcinoma) cell lines showed a
      consistent two- to threefold induction of transcription when stimulated with 1,25
      (OH)2D3. These heterologous promoter transfection studies with gel shift analysis
      locate a third, natural DR6-type vitamin D responsive element (VDRE) at
      nucleotide positions -171 to -154 in the murine FN promoter. Interestingly, this
      VDRE is also present in rat and human FN promoters. This study shows that 1,25
      (OH)2D3 induces FN transcription from an existing elevated basal transcriptional
      activity by acting through two putative hexameric core binding motifs which bind
      VDR homodimers. Furthermore, the FN VDRE is the first homodimer-type VDRE that is
      not overlaid by a DR3-type structure.

PMID- 8867809
TI  - Argininosuccinate synthetase and argininosuccinate lyase are localized around
      mitochondria: an immunocytochemical study.
AB  - Argininosuccinate synthetase and argininosuccinate lyase are soluble cytoplasmic
      enzymes of the urea cycle. Previous biochemical studies using permeabilized
      hepatocytes showed that these enzymes are organized in situ, and function as if
      they are located next to the outer membrane of mitochondria. We have now
      confirmed and extended those observations in intact liver by means of
      immunocytochemistry at the electron microscope level. Morphometric analysis of
      the electron micrographs shows that argininosuccinate synthetase and
      argininosuccinate lyase are located in the immediate vicinity of the
      mitochondria, predominantly next to the cytoplasmic surface of the outer
      membrane. Some immuno-specific protein is also observed in the endoplasmic
      reticulum in the immediate vicinity of the mitochondria. These results support
      our previous biochemical findings, and additionally suggest that virtually all of
      the argininosuccinate synthetase and argininosuccinate lyase of the liver
      parenchymal cell are located just outside the mitochondria.

PMID- 8867810
TI  - Transcriptional downregulation of stromelysin by tetracycline.
AB  - We investigated the role of tetracycline in the transcriptional regulation of
      matrix metalloproteinases. Using interleukin-1beta (IL-1) induced stromelysin as
      a model system, we describe the repression of the endogenous stromelysin RNA
      accumulation, as well as the transcriptional inhibition of various stromelysin
      promoter/chloramphenicol-acetyltransferase constructs in transient transfection
      assays. The inhibition occurred in a dose-dependent fashion, with an IC50 of
      about 1 microM. Our results suggest that the transcriptional inhibition by
      tetracycline is not due to a block of activity of the activating protein complex
      1 (AP-1) but is mediated by sequences upstream of the AP-1 binding site.

PMID- 8867811
TI  - Binding of nuclear proteins to a conserved histone H1t promoter element suggests
      an important role in testis-specific transcription.
AB  - The testis-specific histone H1t gene is transcribed only in primary spermatocytes
      during spermatogenesis. Recently, expression of the rat gene was shown to be
      limited to primary spermatocytes in transgenic mice, revealing that promoter
      elements sufficient for regulating tissue-specific transcription were present in
      the cloned rat gene. In this study the mouse histone H1t gene has been cloned,
      and sequenced and its promoter region has been compared to the rat H1t promoter
      with regard to conserved elements and protein binding activity. The amino acid
      sequence of each of the three H1t coding region domains is conserved when
      compared to the homologous domain in H1t derived from other species. H1t mRNA is
      found only in testis, where it accumulates to a high steady-state level, and
      examination of enriched testis cell populations shows that expression is limited
      to primary spermatocytes. Protein binding assays using nuclear extracts from
      various mouse tissues reveal testis-specific binding to TE1 and TE2, imperfect
      inverted repeat elements within the larger TE element. Although the H1t promoter
      contains an Sp1 consensus motif within the H1t/TE element, binding of testis Sp1
      to the motif could not be detected using specific anti-Sp1 antibodies.

PMID- 8867812
TI  - Inducible expression of cyclin D1 in T-47D human breast cancer cells is
      sufficient for Cdk2 activation and pRB hyperphosphorylation.
AB  - The sequential transcriptional activation of cyclins, the regulatory subunits of
      cell cycle specific kinases, regulates progress through the cell cycle. In
      mitogen-stimulated cells cyclin D1 induction in early G1 is followed by induction
      of cyclin E, activation of the cyclin-dependent kinase Cdk2, and
      hyperphosphorylation of the retinoblastoma gene product (pRB) in mid-to-late G1
      phase. T-47D breast cancer cells expressing cyclin D1 under the control of a
      metal-responsive metallothionein promoter were used to determine whether Cdk2
      activation and pRB hyperphosphorylation are consequences of cyclin D1 induction.
      A 4-5-fold increase in cyclin D1 protein abundance was followed by approximately
      2-fold increases in cyclin E protein abundance and Cdk2 activity and by
      hyperphosphorylation of pRB. These responses were apparent approximately 3 h
      after the increase in cyclin D1 protein, and approximately 3 h prior to the entry
      of cyclin D1-stimulated cells into S phase 12 h after zinc treatment. Cyclin D1
      immunoprecipitates contained Cdk4 but no detectable Cdk2 and displayed pRb but
      not histone H1 kinase activity. Cdk2 activation was therefore likely to be due to
      increased abundance of cyclin E/Cdk2 complexes rather than formation of active
      cyclin D1/Cdk2 complexes. The sequence of events following zinc induction of
      cyclin D1 thus mimicked that following mitogen induction of cyclin D1. These data
      show that cyclin D1 induction is sufficient for Cdk2 activation and pRB
      hyperphosphorylation in T-47D human breast cancer cells, providing evidence that
      cyclin D1 induction is a critical event in G1 phase progression.

PMID- 8867813
TI  - Temporal study of the activity of matrix metalloproteinases and their endogenous
      inhibitors during wound healing.
AB  - The restoration of functional connective tissue is a major goal of the wound
      healing process. This regenerative event requires the deposition and accumulation
      of collagenous and noncollagenous matrix molecules as well as the remodelling of
      extracellular matrix (ECM) by matrix metalloproteinases (MMPs). In this study, we
      have utilized substrate gel electrophoresis, radiometric enzyme assays, and
      Western blot analyses to determine the temporal pattern of appearance and
      activity of active and latent MMPs and their inhibitors during the entire healing
      process in a partial thickness wound model. Through the use of substrate gel
      electrophoresis, we studied the appearance of proteolytic bands whose molecular
      weight was consistent with their being members of the MMP family of enzymes.
      Proteolytic bands whose molecular weight is consistent with both the active and
      latent forms of MMP-2 (72 kDa, Type IV gelatinase) were detected in wound fluid
      of days 1-7 after wounding. The number of active MMP-2 species detectable in
      wound fluid was greatest during days 4-6 after wounding. The most prominent
      proteolytic band detected each day migrated with a molecular weight consistent
      with it being the latent form of MMP-9 (92 kDa, Type V pro-collagenase). In
      contrast to MMP-2, the active form of this enzyme was never detected. The
      presence of MMP-1 (interstitial collagenase) was detected by immunoblot in the
      wound fluid from days 1-6 post-injury. Using a radiometric enzyme assay for
      collagenase inhibitory activity we have also determined the time course of
      activity of endogenous matrix metalloproteinase inhibitors. We have correlated
      these data to the known cellular events occurring in the wound during this time
      period as well. This study establishes a prototypical pattern of MMP appearance
      in normal wound healing. It may also provide potential intervention sites for the
      therapeutic use of inhibitors of aberrant MMP activities which characterize
      chronic wounds.

PMID- 8867814
TI  - Characterization of insulin-like growth factor binding protein-1 kinases from
      human hepatoma cells.
AB  - The phosphorylation of insulin-like growth factor binding protein-I (IGFBP-1)
      alters its binding affinity for insulin-like growth factor I (IGF-I) and thus
      regulates the bioavailability of IGF-I for binding to the IGF-I receptor. The
      kinase(s) responsible for the phosphorylation of IGFBP-1 has not been identified.
      This study was designed to characterize the IGFBP-1 kinase activity in HepG2
      human hepatoma cells, a cell line that secretes IGFBP-1 primarily as
      phosphorylated isoforms. IGFBP-1 kinase activity was partially purified from
      detergent extracts of the cells by phosphocellulose chromatography and gel
      filtration. Two kinases of approximate M(r) 150,000 (peak I kinase) and M(r)
      50,000 (peak II kinase) were identified. Each kinase phosphorylated IGFBP-1 at
      serine residues that were phosphorylated by intact HepG2 cells. The kinases were
      distinct based on their differential sensitivity to inhibition by heparin (IC50 =
      2.5 and 16.5 micrograms/ml, peak I and II kinase, respectively) and inhibition by
      the isoquinoline sulfonamide CKI-7 (IC50 = 50 microM and 100 microM, peak I and
      II kinase, respectively). In addition, a tenfold molar excess of nonradioactive
      GTP relative to [gamma-32P]ATP lowered the incorporation of 32P into IGFBP-1 by
      80% when the reaction was catalyzed by the peak I kinase, whereas GTP had no
      effect on the reaction catalyzed by the peak II kinase. In the presence of
      polylysine, IGFBP-1 was radiolabeled by the partially purified kinase activity
      when [gamma-32P]GTP served as the phosphate donor indicating the presence of
      casein kinase II activity. Furthermore, IGFBP-1 was phosphorylated by purified
      casein kinase I and casein kinase II at sites phosphorylated by the peak I and II
      kinases. Our data suggest that at least two kinases could be responsible for the
      phosphorylation of IGFBP-1 in intact HepG2 cells and that the kinases are related
      to the casein kinase family of protein kinases.

PMID- 8867815
TI  - Molecular cloning of the cDNA of mouse mitochondrial NADP-dependent isocitrate
      dehydrogenase and the expression of the gene during lymphocyte activation.
AB  - The current report documents the molecular cloning of the mouse mitochondrial
      NADP-dependent isocitrate dehydrogenase (mNADP-IDH) cDNA. The cDNA was 1,863 bp
      in length and contained one open reading frame encoding a 523-residue polypeptide
      with a predicted molecular weight of 58 kDa. The cDNA and the deduced amino acid
      (AA) sequence of the mouse mNADP-IDH had a high degree of homology with those of
      porcine, bovine, alfalfa, and yeast. The recombinant mNADP-IDH expressed in
      Escherichia coli had active enzymatic function, as well as an expected molecular
      weight. The heart had the highest constitutive expression of the steady-state
      mNADP-IDH mRNA, followed by the kidney, while the expression of the gene in other
      tissues was low. The enzymatic activity of different tissues was in agreement
      with their mNADP-IDH mRNA levels. The resting lymphocytes had low constitutive
      expression of the gene, but the steady-state mRNA could be induced 48 h after
      mitogen stimulation. At the protein level, the resting lymphocytes had low
      enzymatic activity of mNADP-IDH, but the activity was augmented fivefold after
      mitogen stimulation. The cytosolic NADP-IDH, on the contrary, remained low or
      undetectable before and after the mitogen stimulation. Based on our current
      findings as well as the known roles of the mNADP-IDH in anabolism and in the
      isocitrate shuttle, it is conceivable that the mNADP-IDH is necessary for
      optimizing proliferation in lymphocytes.

PMID- 8867816
TI  - Guanylate cyclase activity in permeabilized Dictyostelium discoideum cells.
AB  - Dictyostelium discoideum cells respond to chemoattractants by transient
      activation of guanylate cyclase. Cyclic GMP is a second messenger that transduces
      the chemotactic signal. We used an electropermeabilized cell system to
      investigate the regulation of guanylate cyclase. Enzyme activity in permeabilized
      cells was dependent on the presence of a nonhydrolysable GTP analogue (e.g., GTP
      gamma S), which could not be replaced by GTP, GDP, or GMP. After the initiation
      of the guanylate cyclase reaction in permeabilized cells only a short burst of
      activity is observed, because the enzyme is inactivated with a t1/2 of about 15
      s. We show that inactivation is not due to lack of substrate, resealing of the
      pores in the cell membrane, product inhibition by cGMP, or intrinsic instability
      of the enzyme. Physiological concentrations of Ca2+ ions inhibited the enzyme
      (half-maximal effect at 0.3 microM), whereas InsP3 had no effect. Once
      inactivated, the enzyme could only be reactivated after homogenization of the
      permeabilized cells and removal of the soluble cell fraction. This suggests that
      a soluble factor is involved in an autonomous process that inactivates guanylate
      cyclase and is triggered only after the enzyme is activated. The initial rate of
      guanylate cyclase activity in permeabilized cells is similar to that in intact,
      chemotactically activated cells. Moreover, the rate of inactivation of the enzyme
      in permeabilized cells and that due to adaptation in vivo are about equal. This
      suggests that the activation and inactivation of guanylate cyclase observed in
      this permeabilized cell system is related to that of chemotactic activation and
      adaptation in intact cells.

PMID- 8867817
TI  - Regulation of cytoplasmic tubulin carboxypeptidase activity in vitro by cations
      and sulfhydryl-modifying compounds.
AB  - alpha-tubulin subunits within microtubules (MTs) can be post-translationally
      detyrosinated by a tubulin-specific carboxypeptidase (TCP) activity to form
      biochemically distinct MTs. Attempts to characterize and purify TCP have suffered
      from the inability to detect low levels of activity and to distinguish TCP from
      other, competing enzyme activities. We recently developed an assay for TCP
      [Webster et al. (1992) Biochemistry 31:5849] that uses taxol-stabilized MTs as
      the substrate. In this study, we exploited the increased sensitivity and
      specificity of this new assay to explore the effects of various agents that might
      act to either stimulate or inhibit this enzyme in vitro. We tested a variety of
      both monovalent and divalent cations for their ability to affect TCP, and tested
      whether the cations were affecting the enzyme, the substrate, or both. We found
      that TCP displayed salt-sensitive binding to MTs, characteristic of other, more
      well characterized MT-associated proteins. While both calcium and magnesium
      stimulated TCP activity over a narrow concentration range (2-10 mM), they
      inhibited activity at higher concentrations. Other divalent cations tested,
      including zinc, copper, and cobalt, inhibited TCP at virtually all concentrations
      tested, but to different levels (zinc > copper > cobalt). Most of the zinc
      induced TCP inhibition was attributed to the interference with the normal binding
      of TCP to MTs. In addition, we examined the involvement of free sulfhydryl groups
      (which are important for the activities of many types of enzymes) in TCP activity
      by the addition of sulfhydryl-modifying compounds during the assay, and found
      that their addition reduced TCP activity mainly (but not solely) by their action
      on the extract that contained the TCP. Finally, we tested the ability of DL
      benzylsuccinic acid, a potent inhibitor of carboxypeptidase A, to inhibit TCP.
      While carboxypeptidase A has been found, in other studies, to be inhibited by
      micromolar concentrations, TCP was affected only at concentrations above 20 mM,
      adding another proof that carboxypeptidase A and TCP are distinct enzyme
      activities.

PMID- 8867818
TI  - Interactions of neurotransmitters and endothelial cells in determining vascular
      tone.

PMID- 8867819
TI  - Some recent advances in studies on J receptors.
AB  - While describing recent advances in studies on J receptors it was shown that the
      discovery of the principle of the relative dilution of multiple solutes in
      flowing fluids paved the way for developing a new method for measuring in vivo
      the concentration of injected drugs in the blood of the pulmonary artery. This
      led to the finding that excitatory solutes move out of the capillaries through a
      process of diffusion not through filtration. Increase in the permeability of the
      capillaries causes a marked increase in the responses of the J receptors to
      excitants by causing greater movement of the excitants to the receptors. This
      information is likely to yield a method for distinguishing permeability edema
      from hamodynamic edema in man. The most recent advance relates to the evidence
      showing conclusively that the sensations and dry cough produced by injecting
      lobeline intravenouly in man is due to the stimulation of the J receptors. The
      slowly and rapidly adapting receptors play little or no role in this. The nature
      of the sensations felt is somewhat variable, most commonly it is choking and
      pressure localised in the throat and upper chest. Similar sensations are felt by
      subjects with high altitude pulmonary edema (HAPE). From this data it is
      extrapolated that the same kinds of sensations that accompany breathlessness
      after moderate or severe exercise at sea level are also J receptor induced.

PMID- 8867820
TI  - Pathophysiology of bronchial asthma.

PMID- 8867821
TI  - Upper airway influences on breathing.

PMID- 8867822
TI  - Activation of protein kinase C mediates insulin regulation of the Na-K pump in
      cultured skeletal muscle.

PMID- 8867823
TI  - Aortic and abdominal glomera.

PMID- 8867824
TI  - Postnatal development of hypoglossal motoneuron intrinsic properties.
AB  - This review has provided evidence that marked changes are occurring in ionic
      currents present in upper airway motoneurons during the early postnatal period.
      Our results have shown that the density of the LVA Ca2+ current decreases during
      this period, and this probably reflects a reduced expression of the Ca2+ channel
      responsible for this current, the so-called T-type channel. These results help to
      explain the changes in burst firing behavior of HMs during the early postnatal
      period. We have shown that the fraction of HMs exhibiting burst firing behavior
      was the greatest among HMs just at or after birth, and disappeared by 10 days of
      age (Viana et al, 1993). The LVA Ca2+ current contributes to this firing
      behavior. In contrast to the reduction in the LVA Ca2+ current density with
      postnatal development, there is an apparent increase in Ih current density during
      this period. The increase in Ih provides a basis for a number of differences in
      the electrophysiological properties of adult versus neonate HMs. These include a
      striking depolarizing sag and overshoot during and immediately after application
      of hyperpolarizing current pulses in adult HMs. It is of interest that rebound
      depolarization following hyperpolarization can be observed in neonatal HMs even
      though there is little Ih present. This response probably reflects the activation
      of a LVA Ca2+ current. Other differences in neonate versus adult HMs also are in
      part probably due to differences in Ih current density. Since Ih is active at
      normal resting membrane potential (approximately -70 mV), Ih may contribute to
      the lower input resistance of adult compared with neonatal HMs (Haddad et al,
      1990; Nunez-Abades et al, 1993; Viana et al, 1994), and the lower apparent
      membrane resistivity of older HMs (Viana et al 1994). The larger Ih in the adult
      may be a factor in the shorter spike afterhyperpolarization observed in adult
      versus neonatal HMs (Viana, et al, 1994). This may be a consequence of the
      greater amount of Ih activated during the afterhyperpolarization in adult HMs.
      The larger Ih in adult HMs may also contribute to differences in how synaptic
      inputs are integrated. For example, inhibitory inputs which hyperpolarize the
      membrane potential may have their effect lessened due to Ih activation with
      hyperpolarization. Thus in adult HMs Ih may weaken prolonged or strong
      hyperpolarizations that occur in response to inhibitory synaptic inputs, while
      depolarizing responses arising from excitatory synaptic inputs may not be
      compromised. In contrast, neonatal HMs, which lack a substantial Ih current, do
      not have the stabilizing influence upon membrane potential that is due to Ih.
      Therefore, these cells may be more susceptible to such inhibitions. In
      conclusion, this chapter has described the changes that take place in two ionic
      currents during postnatal development, and how they contribute to distinct
      subthreshold and firing properties of neonatal and adult motoneurons.

PMID- 8867825
TI  - Central nervous mechanisms responsible for cardio-respiratory homeostasis.

PMID- 8867826
TI  - Neuroendocrine regulation of vascular capacitance.

PMID- 8867827
TI  - The microphysiology of lung liquid clearance.

PMID- 8867828
TI  - Cardiac receptor activity in heart failure: implications for the control of
      sympathetic nervous outflow.

PMID- 8867829
TI  - Atrial receptors and heart volumes.
AB  - So now we have a view of the circulation in exercise in the upright posture. The
      output of the heart depends on the input which is driven by the muscle pumps
      mainly from the lower limbs but augmented by the upper limbs, and the thoracic
      and abdominal muscles. The heart thus receives an increasing inflow of blood but
      the heart volumes change comparatively little-only over a very small range of
      values. Physiologists, in animals and man, have measured changes in cardiac
      output and heart volumes-it is difficult to be precise about the results but we
      can agree on order of magnitude. Cardiac output can increase 5, 6 or 7 times in
      trained athletes but the stroke volume never more than doubles, the end-diastolic
      volume increases only 50% and the end-systolic volume decreases by about the same
      amount (16,43). The heart rate increases about 2 1/2 times in the untrained to 5
      times in the trained physically fit athlete. It would also seem that the main
      influence causing an increase in heart size is an increase in venous return
      mainly caused by the muscle pumps. An increase in activity in sympathetic nerves
      to the heart muscle forms a mechanism which assists in the control of heart
      volumes, decreasing end-systolic volume and increasing stroke volume. It is not
      known what causes this increase in sympathetic activity during exercise but it
      may just be concomitant with the increase in activity in nerves to the skeletal
      muscles and originate in a similar area of the brain. There also seems no doubt
      that as the heart rate increases, with no other concomitant changes, the heart
      volumes decrease. Thus is may concluded that any increase in heart rate during
      exercise would limit the increase in the size of the heart which results from the
      increase in venous return. Next we must consider mechanisms which might affect
      the two efferent nerves to the heart, the sympathetic and the vagal nerves, these
      being the final common path of changes in heart rate.

PMID- 8867830
TI  - Aspects of coronary vasomotor regulation.

PMID- 8867831
TI  - Graded restriction of blood flow in exercising leg muscles: a human model.

PMID- 8867832
TI  - Cardiovascular reflexes from ventricular and coronary receptors.
AB  - Ventricular receptors are distributed throughout the left ventricle and most, if
      not all, are attached to nonmyelinated nerve fibers. The receptors may be
      chemosensitive, mechanosensitive or both. Chemosensitive afferents are
      classically excited by exogenous chemicals such as veratridine, although
      endogenous chemicals such as bradykinin and prostaglandins, which are released
      during ischemia, also excite these nerves. The reflex responses can be very
      powerful, resulting in profound bradycardia and hypotension. A normal
      physiological role for these receptors seems unlikely although it is probable
      that they contribute to the changes occuring in some pathological states.
      Ventricular mechanoreceptors, some of which may also exhibit chemosensitivity,
      are excited by increases in ventricular systolic pressure, but only when the
      pressure increases to extreme levels. They also appear to react to increases in
      inotropic state and increases, and possibly also to decreases, in ventricular
      filling. It seems that ventricular mechanoreceptors do not show the same intense
      response as is seen in the chemosensitive afferents following chemical
      stimulation and probably as a consequence of this their reflex responses are also
      weak and probably of little importance. Previous assertions that they are
      involved in the vasovagal reaction can probably now be discounted. The existence
      of coronary arterial baroreceptors has been suspected for about 30 years. This
      has now been confirmed and they have been shown to respond to pressure changes in
      much the same way as the well known carotid and aortic baroreceptors. There are,
      however, some interesting differences. Coronary baroreceptors, at least in the
      dog, do not control the heart rate, although they do influence respiratory
      activity. Another intriguing difference is that when vascular resistance has been
      inhibited reflexly by perfusing coronary receptors at a high pressure, it takes
      several minutes for the vascular resistance to increase when coronary pressure is
      again lowered. The implications of this are uncertain, but it is conceivable
      that, whereas carotid baroreceptors are involved in the responses to rapid
      changes in pressure, coronary baroreceptors may be more concerned with the
      regulation of the long-term level of arterial blood pressure.

PMID- 8867833
TI  - Mechanisms of release of atrial natriuretic factor in vivo.
AB  - The aim of the study was to define the relationship between the concentration of
      immunoreactive atrial natriuretic factor (ANF) in the plasma and atrial stretch,
      atrial pressure and atrial wall stress during changes in blood volume within the
      physiological range. Advantage was taken of the potentiation of the release of
      ANF, in response to blood volume expansion, in the anaesthetized rabbit, by
      section of the carotid sinus, aortic depressor and vagus nerves. Mean arterial
      pressure and right and left atrial pressures were measured. Right and left atrial
      dimensions were measured by sonomicrometry. Blood volume was expanded by 20% and
      then decreased at 1% of the blood volume per minute for 40 min, before and after
      section of the nerves. Plasma ANF did not change significantly in response to
      either the increase or decrease in blood volume in the presence of intact nerves.
      After the nerves were sectioned, blood volume expansion significantly increased
      IR-ANF (34.6 +/- 12 to 260.6 +/- 89.8 pg/ml). The relationship between ANF and
      the changes in left atrial dimensions (extension ratio) was exponential. A
      significant linear correlation was found between ANF and left atrial pressure and
      left atrial wall stress. Over a range of atrial pressures from 1-10 cm H2O the
      atrial wall was extremely distensible, but there were only minor changes in ANF.
      At higher atrial pressures there was little further extension of the atrial wall
      but there were much larger increases in plasma ANF. In response to changes in
      blood volume within the physiological range cardiovascular reflexes normal
      maintain atrial dynamic function within a narrow range and there is little
      stimulus for the release of ANF. In conditions in which the cardiovascular
      reflexes are unable to maintain atrial function constant then there will be
      changes in the release of ANF and there will be an exponential relationship
      between atrial wall stretch and plasma ANF.

PMID- 8867834
TI  - Exercise pressor reflex: studies on the effect of skeletal muscle fiber type and
      spinal cord transmission.

PMID- 8867835
TI  - A lifetime of research in integrative physiology.

PMID- 8867836
TI  - Mechanisms underlying spinal neuromodulation of the exercise pressor reflex.

PMID- 8867837
TI  - The role of vasopressin and angiotensin II in the hemodynamic response to dynamic
      exercise.

PMID- 8867838
TI  - Vitamin analysis using capillary zone electrophoresis.

PMID- 8867839
TI  - A flexible motif search technique based on generalized profiles.
AB  - A flexible motif search technique is presented which has two major components:
      (1) a generalized profile syntax serving as a motif definition language; and (2)
      a motif search method specifically adapted to the problem of finding multiple
      instances of a motif in the same sequence. The new profile structure, which is
      the core of the generalized profile syntax, combines the functions of a variety
      of motif descriptors implemented in other methods, including regular expression
      like patterns, weight matrices, previously used profiles, and certain types of
      hidden Markov models (HMMs). The relationship between generalized profiles and
      other biomolecular motif descriptors is analyzed in detail, with special
      attention to HMMs. Generalized profiles are shown to be equivalent to a
      particular class of HMMs, and conversion procedures in both directions are given.
      The conversion procedures provide an interpretation for local alignment in the
      framework of stochastic models, allowing for clear, simple significance tests. A
      mathematical statement of the motif search problem defines the new method exactly
      without linking it to a specific algorithmic solution. Part of the definition
      includes a new definition of disjointness of alignments.

PMID- 8867840
TI  - Evolution of simple sequence repeats.
AB  - Simple Sequence Repeats (SSRs) are common and frequently polymorphic in eukaryote
      DNA. Many are subject to high rates of length mutation in which a gain or loss of
      one repeat unit is most often observed. Can the observed abundances and their
      length distributions be explained as the result of an unbiased random walk,
      starting from some initial repeat length? In order to address this question, we
      have considered two models for an unbiased random walk on the integers, n (n0 <
      or = n). The first is a continuous time process (Birth and Death Model or BDM) in
      which the probability of a transition to n + 1 or n - 1 is lambda k, with k = n -
      n0 + 1 per unit time. The second is a discrete time model (Random Walk Model or
      RWM), in which a transition is made at each time step, either to n - 1 or to n +
      1. In each case the walks start at length n0, with new walks being generated at a
      steady rate, S, the source rate, determined by a base substitution rate of
      mutation from neighboring sequences. Each walk terminates whenever n reaches n0 -
      1 or at some time, T, which reflects the contamination of pure repeat sequences
      by other mutations that remove them from consideration, either because they fail
      to satisfy the criteria for repeat selection from some database or because they
      can no longer undergo efficient length mutations. For infinite T, the results are
      particularly simple for N(k), the expected number of repeats of length n = k + n0
      - 1, being, for BDM, N(k) = S/k lambda, and for RWM, N(k) = 2S. In each case,
      there is a cut-off value of k for finite T, namely k = T lambda ln2 for BDM and k
      = 0.57 square root of T for RWM; for larger values of k, N(k) becomes rapidly
      smaller than the infinite time limit. We argue that these results may be compared
      with SSR length distributions averaged over many loci, but not for a particular
      locus, for which founder effects are important. For the data of Beckmann & Weber
      [(1992), Genomics 12, 627] on GT.AC repeats in the human, each model gives a
      reasonable fit to the data, with the source at two repeat units (n0 = 2). Both
      the absolute number of loci and their length distribution are well represented.

PMID- 8867841
TI  - Theoretical approaches to the analysis of homeobox gene evolution.
AB  - The homeobox gene system presents a unique model for experimental and theoretical
      analyses of gene evolution. Homeobox genes play a role in patterning the
      embryonic development of diverse organisms and as such are likely to have been
      fundamental to the evolution of the specialized body plans of many animal
      species. The organization of Hox-genes in chromosomal, clusters in many species
      implicates gene duplication as a prominent mechanism in the evolution of this
      multigene family. I review here various theoretical analyses that have
      contributed to our understanding of the molecular evolution of this class of
      developmental control genes. This article also illustrates relationships between
      theoretical predictions and experimental studies and outlines future avenues for
      the evolutionary analysis of developmental systems.

PMID- 8867842
TI  - Improving the analysis of phylogenetic data.
AB  - Methods of phylogenetic analysis are presented that result in corrections of
      highly biased data sets, particularly those in which there are great differences
      between mutation and/or substitution rates from one nucleotide site to another
      along a DNA sequence. Two approaches are discussed. In the first, pairwise
      comparisons of a set of sequences are used to determine whether the most recent
      substitutions take place at the sites that are most polymorphic--that is, where
      the mutational "hot spots" are located. In the second, a "topiary pruning" method
      is used to remove selectively the bases in the data set that are most likely to
      occupy these hot spots and therefore to result in homoplastic substitutions. The
      two methods combined yield new and substantially older estimates of the time at
      which the mitochondrial Eve lived, and increase the likelihood that she lived in
      Africa. In these data, transversions provide a more satisfactory yardstick for
      phylogenetic analysis than transitions, because there is no detectable tendency
      for transversions to occur at mutational hot spots.

PMID- 8867843
TI  - CENSOR--a program for identification and elimination of repetitive elements from
      DNA sequences.
AB  - CENSOR is a program designed to identify and eliminate fragments of DNA sequences
      homologous to any chosen reference sequences, in particular to repetitive
      elements. CENSOR is based on two principal algorithms of Smith & Waterman (1981)
      [J. Mol. Biol. 147, 195] and Wilbur & Lipman (1983) [Proc. Natl. Acad. Sci.
      U.S.A. 80, 726]. It includes several pre-set sensitivity levels based on both
      biological and statistical criteria which help to distinguish between aligned
      pairs of homologous and non-homologous sequences. CENSOR has been implemented in
      C/C + + in the SUN/UNIX environment.

PMID- 8867844
TI  - Detection of RNA polymerase II promoters and polyadenylation sites in human DNA
      sequence.
AB  - Detection of RNA polymerase II promoters and polyadenylation sites helps to
      locate gene boundaries and can enhance accurate gene recognition and modeling in
      genomic DNA sequence. We describe a system which can be used to detect
      polyadenylation sites and thus delineate the 3' boundary of a gene, and discuss
      improvements to a system first described in Matis et al. (1995) [Matis S., Shah
      M., Mural R. J. & Uberbacher E.C. (1995) Proc. First Wrld Conf. Computat. Med.,
      Public Hlth, Biotechnol. (Wrld Sci.) (in press).], which predicts a large subset
      of RNA polymerase II promoters. The promoter system used statistical matrices and
      distance information as inputs for a neural network which was trained to provide
      initial promoter recognition. The output of the network was further refined by
      applying rules which use the gene context information predicted by GRAIL. We have
      reconstructed the rule-based system which uses gene context information and
      significantly improved the sensitivity and selectivity of promoter detection.

PMID- 8867845
TI  - Databases of mRNA untranslated regions for metazoa.
AB  - The important role that untranslated regions of mRNAs (UTR) may play in gene
      regulation and expression is now widely accepted. For this reason we developed
      UTRDB, a specialized database of 5'- and 3'-UTR of eukaryotic mRNAs cleaned of
      redundancy. This paper describes the composition and the general feature of
      UTRDB. The analysis of UTRDB by using suitable statistical methods could provide
      useful information for guiding the experimental work aimed at delucidating the
      role of UTR sequences in gene regulation and expression.

PMID- 8867846
TI  - Membrane unpacking and the rapid disposal of apoptotic cells.
AB  - There is evidence that macrophages can recognize phosphatidylserine (PS) on the
      surface of apoptotic thymocytes, where PS exposure relates to looser packing
      ('unpacking') of the polar headgroups of the outer lamina, detectable by
      lipophilic dyes (Fadok, V.A., Voelker, D.R., Campbell, P.A., Cohen, J.J.,
      Bratton, D.L. and Henson, P.M. (1992) J. Immunol. 148, 2207). We have shown that
      membrane unpacking also occurs in B cells, where this event actually precedes DNA
      cleavage (Mower, D.A. Jr., Peckham, D.W., Illera, V.A., Fishbaugh, J.K., Stunz,
      L.L. and Ashman, R.F. (1994) J. Immunol. 152, 4832). This paper demonstrates that
      the time interval between membrane unpacking (detected as merocyanine 540
      binding) and DNA cleavage (detected by flow cytometry of propidium iodide stained
      nuclei) also occurs in both T cells and thymocytes. The tight coupling of these
      two apparently distinct events is emphasized by their co-regulation by a variety
      of agents which accelerate or inhibit apoptosis. One hypothesis to explain the
      very low numbers of free apoptotic cells seen in vivo is that macrophages can
      recognize cells with unpacked membranes and destroy them before they cleave their
      DNA. In support of this hypothesis, we demonstrated that parenteral cycloheximide
      triggers a wave of apoptosis in the spleen detected by merocyanine 540 as well as
      by hypodiploid nuclei. Significantly, both parameters returned from peak values
      at 2 h virtually to normal by 4 h, testifying to the existence of a rapid
      disposal mechanism in vivo for cells with unpacked membranes as well as
      hypodiploid nuclei.

PMID- 8867847
TI  - Phenotypic and functional characteristics of in vivo-induced interleukin-12
      activated killer cells.
AB  - A single i.p. administration of IL-12 (2000 U/mouse) into the mice caused the
      elevation of serum IFN-gamma activity and the generation of killer cells which
      can lyse various kinds of tumor cells including both NK-sensitive and -resistant
      tumor cells. Such in vivo induced killer cells were not detected in the mice
      treated with the same dose of IL-2. The generation of IL-12-activated killer
      cells (IL-12AK) peaked at day 1 and sustained their cytotoxicity until day 3
      after IL-12 administration. The generation of IL-12AK was inhibited by in vivo
      administration of anti-asialo GM1 (ASGM1) Ab but not anti-CD4 or anti-CD8 mAbs,
      suggesting that the precursor cells for IL-12AK were ASGM1+CD4-CD8- NK cells. The
      phenotypic characterization of in vivo induced effector cells with IL-12AK
      activity was carried out by separating the cells with FACStar. The IL-12AK
      activity was highly enriched in ASGM1+CD4-8- or NK1.1+CD4-8- NK cells, but not in
      CD8+ T cells and CD4+ T cells. The IL-12AK cells were also generated in tumor
      inoculated mice. In parallel with the in vivo generation of IL-12AK generation,
      the growth of i.p. inoculated MBL-2 lymphoma cells was markedly inhibited by the
      administration with IL-12. The in vivo antitumor activity of IL-12 was blocked by
      the administration of anti-ASGM1 but not anti-CD4 or anti-CD8 mAbs in concomitant
      with the decrease of IL-12AK generation. From these results, it was indicated
      that ASGM1+NK1.1+CD4-8- NK type IL-12AK cells might play an important role in IL
      12-induced local therapy of tumor in vivo.

PMID- 8867848
TI  - Short-term culture of surface-biotinylated cells: application in non-radioactive
      analysis of surface protein shedding.
AB  - As an alternative to radiolabelling, cell surface biotinylation followed by
      immunoprecipitation and enhanced chemiluminescence detection can be used to
      characterize membrane-bound surface proteins. Since many membrane proteins are
      known to be shed from the surface, we tested whether surface biotinylation can
      also be used to characterize these soluble proteins released into culture
      supernatant. First, we found that biotinylated cells could be cultured for up to
      7 days without any influence on viability and 3H-thymidine incorporation.
      Moreover, the PHA response (3H-thymidine incorporation) of peripheral blood
      mononuclear cells was affected only by high concentrations of the biotinylation
      reagent N-hydroxysuccinimidobiotin and the LPS response (cytokine release) was
      unaffected by surface biotinylation. Second, we were able to monitor the shedding
      of biotinylated HLA class I antigens from Balm 1 cells by immunoprecipitation,
      SDS-PAGE, and enhanced chemiluminescence detection on blots. Membrane-bound HLA
      class I antigens disappeared from the cell surface during 5-day culture and,
      simultaneously, two forms of soluble HLA class I heavy chains (36 and 44 kDa)
      accumulated in the culture supernatant. Thus, short-term culture of surface
      biotinylated cells can be used in the analysis of the shedding processes of
      leukocyte antigens.

PMID- 8867849
TI  - The role of cis-urocanic acid in UVB-induced suppression of contact
      hypersensitivity.
AB  - Ultraviolet light B (UVB) is well recognized to suppress the contact
      hypersensitivity (CHS) response and it has been postulated that cis-urocanic acid
      (UCA) is a mediator of the immunosuppression. This study was designed to examine
      the effect of UCA on CHS and to clarify its role in UVB-induced immunosuppression
      in C57BL/6 mice. Intradermal injection of 0.5-50 micrograms cis-UCA into the ear
      2 h before DNFB sensitization resulted in a 60-70% reduction of CHS assessed by
      ear swelling, whereas trans-UCA did not have a significant effect on CHS except
      at a high dose (50 micrograms) which showed a 20-40% suppression. Intraperitoneal
      injection of anti-cis-UCA antibody before administration of cis-UCA abrogated the
      suppression. To examine the effect of UCA on UVB-induced immunosuppression, some
      mice were pre-treated with anti-cis-UCA antibody and then exposed to UVB (960
      J/m2). After 3 days the mice were sensitized either on the irradiated abdominal
      skin or on the unirradiated dorsal surface of the right ear followed by the
      challenge on the left ear. The CHS response was significantly suppressed in UVB
      irradiated mice both locally (abdominal sensitization, suppression was 45%, P <
      0.001) and systemically (ear sensitization, suppression was 53%, P < 0.0025). The
      CHS response was partially restored in both abdominal sensitized mice and ear
      sensitized mice by pre-treatment with anti-cis-UCA antibody. These results
      confirmed the immunosuppressive effects of cis-UCA on CHS and suggest that cis
      UCA plays a role in UVB-induced local and systemic immunosuppression.

PMID- 8867850
TI  - Monoclonal antibodies recognize 2300 years aged alkaline phosphatase.
AB  - It was attempted to monitor the immunological response of monoclonal antibodies
      directed to human alkaline phosphatase in ancient Egyptian bones from the
      ptolemeic period. The intactness of the respective epitopes of the bone enzyme
      was successfully demonstrated in an ELISA. Fortunately, the mummified bone was
      not contaminated by fungi and bacteria due to the fungicidal and bactericidal
      reactivity of the ancient pretreatment employing resins of pistachio for
      mummification. The enzyme was enriched using gel chromatography, anion exchange
      and affinity chromatography to yield 310 +/- 7 mU/mg. The enzymically active
      fractions of the wheat-germ lectin affinity chromatography were subjected to
      ELISA. The best binding affinity was detected using the monoclonal antibody BAP A
      while the reactions of all the other four antibodies BAP B, BAP G, BAP 4A5 and
      BAP 5D4 were substantially diminished.

PMID- 8867851
TI  - Trypanosoma cruzi: analysis of cellular and humoral response against a protective
      recombinant antigen during experimental Chagas' disease.
AB  - In previous studies we have shown the protective value of T. cruzi
      excretory/secretory antigens (ESA) as well as a synthetic peptide derived from
      the primary sequence of a 24-kDa protein present among ESA in mice and rats
      challenged with a lethal dose of T. cruzi. In the present study, the 24-kDa
      polypeptide was produced as a fusion protein in the pGEX-2T vector system.
      Western blot assays revealed that Tc24 is expressed by all T. cruzi strains so
      far examined (CL, ECH, C23, Tehuantepec, Tulahuen, and Y). The immunization of
      BALB/c mice with Tc24 fusion protein showed that the protein has the capacity to
      induce a significant level of protection in BALB/c mice against lethal T. cruzi
      infection. Moreover, splenic cells from T. cruzi chronically infected mice
      recognize the recombinant antigen since they proliferate after in vitro
      stimulation. A typical Th1 pattern of lymphokine secretion (IL-2 and IFN-gamma)
      was detected in splenic cell culture supernatants from Tc24-immunized mice. In
      addition, high levels of IFN-gamma were detected in cell culture supernatants
      from both acute and chronically infected mice after Tc24 antigen stimulation. In
      contrast, no detectable amounts of IL-4, IL-5 or Th-10 could be detected in those
      supernatants. Finally, antibodies (IgG isotype) involved in the immune clearance
      of T. cruzi are elicited by the Tc24 recombinant protein. Taken together, these
      results demonstrated that the recombinant T. cruzi antigen is able to induce
      cellular and humoral immune responses which could explain the protection achieved
      when this protein is used as immunizing agent.

PMID- 8867852
TI  - Tryptophanyl-tRNA synthetase as a human autoantigen.
AB  - Autoantibodies to highly purified tryptophanyl-tRNA synthetase, consisting of two
      approximately 60-kDa subunits (6.1.1.2, TrpRS), were detected in some sera of
      donors and patients with various diagnosis using the newly developed 125I-TrpRS
      radiodot, 125I-TrpRS-radioblot, ELISA and Western immunoblotting. The percentage
      of positive sera appears to be dependent upon the method of sera testing. The
      autoimmune sera recognized both the native and denatured TrpRS forms. The binding
      of the human serum to the 60-kDa band of tissue extract was demonstrable by the
      125I-TrpRS-blot as well as Western blot techniques. The possible role of
      infections in the induction of anti-TrpRS antibodies and maintenance of the
      autoimmune response is discussed.

PMID- 8867853
TI  - Mapping of the linear antigenic determinants from the Leishmania infantum histone
      H2A recognized by sera from dogs with leishmaniasis.
AB  - Antibodies reacting against the H2A histone protein were frequently observed in
      the sera from dogs naturally infected with the protozoan parasite Leishmania
      infantum. Using synthetic peptides covering the complete sequence of the protein
      we have identified the amino terminal region, comprising from amino acids 1 to
      20, and the carboxyl terminal region, comprising from amino acids 106 to 132, as
      conforming the antigenic determinants of the protein. Those regions, exposed in
      the nucleosome surface, are highly divergent in sequence relative to the
      mammalian H2A histones. The anti-H2A histone antibodies present in the sera of
      these dogs specifically recognize the L. infantum H2A histone and they do not
      react with mammalian histones. The present data indicate that, in spite of the
      evolutionary conservation of the H2A histone protein among eukaryotic organisms,
      the humoral response against this protein during natural infection is
      specifically triggered by the parasite protein antigenic determinants.

PMID- 8867854
TI  - Native DNA fragments photocrosslinked to psoralen binds to anti-B and anti-Z DNA
      antibodies.
AB  - Calf thymus DNA fragments of varying size (100-600 bp) were covalently linked to
      psoralen in the presence of 365 nm UV light. The crosslinked species were
      separated from the monoadducts by hydroxyapatite column chromatography. The DNA
      psoralen crosslink showed binding with naturally occurring anti-DNA
      autoantibodies. This was substantiated by the recognition of affinity purified
      IgG by DNA-psoralen crosslinks of varying DNA size. The photo-crosslinks
      exhibited considerable recognition of both monoclonal and polyclonal anti-Z-DNA
      antibodies in inhibition ELISA and band shift assay.

PMID- 8867856
TI  - Cancer vaccines in gene therapy.

PMID- 8867855
TI  - A novel and basic mechanism of immunosuppression in Chagas' disease: Trypanosoma
      cruzi releases in vitro and in vivo a protein which induces T cell
      unresponsiveness through specific interaction with cysteine and glutathione.

PMID- 8867857
TI  - Prophylactic gene therapy for cancer.
AB  - Attempts at cancer gene therapy to date have focused on the treatment of existing
      neoplasms, using genetic techniques either to target toxic compounds at or
      enhance the host's response to a tumour. These cytotoxic and immunological
      approaches have to be tailored to a specific tumour, and often fail because new
      cellular mutations can overcome the treatment, as for traditional lines of
      therapy. There has been less attention given to the possibility of using gene
      therapy to prevent malignant transformation in certain specific contexts for high
      risk tissues. Such approaches could add functional proto-oncogenes or tumour
      suppressor genes, or nullify pathogenic mutations in such genes using antisense
      or gene replacement techniques. These strategies will not apply to all tumours,
      but are more likely to be effective where tissue-specific stem cells can be
      targeted, and for tumours where mutations in one of several genes are involved in
      carcinogenesis, as for cancer of the colon. Safer vectors for gene delivery will
      also be required if therapy is to be considered for prevention rather than
      treatment.

PMID- 8867858
TI  - Biological response of nonhuman primates to long-term repeated lung exposure to
      Ad2/CFTR-2.
AB  - We have assessed the safety and efficacy of repeated adenovirus vector
      administration by exposing the left caudal lung lobe of rhesus monkeys to as many
      as 17 exposures of Ad2/CFTR-2. After nine doses of either 3 x 10(9) or 3 x 10(10)
      infectious units, the monkeys were free of adverse effects as assessed by
      thoracic radiographs, CBCs, clinical chemistries, arterial blood gases, and
      physical and clinical signs. In some animals elevated protein levels and
      increased numbers of cells were recovered in bronchoalveolar lavage (BAL), and in
      all animals there were increased proportions of lymphocytes in the BAL. After 11
      doses, two animals were killed. In the lower dose animal (3 x 10(9) IU), there
      was little histopathology evident. In the higher dose animal (3 x 10(10) IU),
      histopathology was largely confined to a focal fibrotic lesion that may have been
      associated with treatment. At the tenth exposure, the dose was increased to 6 x
      10(10) or 3 x 10(11) IU. There was evidence of lung injury by thoracic
      radiographs after two additional exposures and an increase in protein and number
      of cells in the BAL. The animals were still free of evidence of adverse effects
      by other parameters, but histopathologic changes were noted upon death. After 15
      or 17 doses, three animals were instilled with Ad2/beta gal-2 and killed 3 days
      later. These animals had greatly reduced levels of transgene expression when
      compared with controls.

PMID- 8867859
TI  - Humoral and cellular immune responses of nonhuman primates to long-term repeated
      lung exposure to Ad2/CFTR-2.
AB  - To evaluate the host immune response to long-term repeat administration of
      adenovirus vector, rhesus monkeys were treated at intervals of approximately 3
      weeks with up to 18 instillations of Ad2/CFTR-2, a second generation vector
      encoding the cystic fibrosis transmembrane conductance regulator (CFTR). All
      monkeys instilled with Ad2/CFTR-2 developed a significant humoral immune response
      against adenovirus but not CFTR. Antibodies with virus neutralizing activity were
      detected in the serum and bronchoalveolar lavage (BAL) of all vector-treated
      monkeys and included both IgG and secretory IgA. Virus-specific T cells capable
      of proliferating in response to stimulation with adenovirus antigen were detected
      in all vector-treated monkeys. No CFTR-specific proliferation of peripheral blood
      lymphocytes was detected. An increase in the proportion of CD8+ T cells was noted
      in the BAL of virus-treated monkeys but cells from the BAL displayed little or no
      cytolytic activity against infected autologous fibroblasts when tested under a
      variety of culture conditions. However, MHC-restricted cytolytic activity was
      detected in the tracheobronchial lymph nodes and spleen of one of three virus
      treated monkeys tested. MHC-unrestricted killing of infected fibroblasts was also
      observed with spleen cells from all animals tested. From these results, it
      appears that both the humoral and cell-mediated arms of the immune response were
      stimulated by repeated administration of high doses of Ad2/CFTR-2 suggesting that
      effective, long-term adenovirus gene therapy may require modification of the
      vector or treatment of the host to allow the virus to evade host immune defenses.

PMID- 8867860
TI  - Evidence for localization of biologically active recombinant retroviral vector to
      lymph nodes in mice injected intramuscularly.
AB  - We have developed a novel gene transfer drug, HIV-IT(V), for the treatment of HIV
      infection in humans. HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env
      and rev genes and a neomycin resistance marker gene (neor). We have recently
      reported that HIV-IT(V) administered intramuscularly to male mice localizes
      primarily to the site of injection. In this study, we have investigated more
      extensively the localization and biological activity of HIV-IT(V) administered
      intramuscularly to female mice. Consistent with our previous findings, retroviral
      DNA was detected by PCR at the site of injection. Retroviral DNA was also
      detected in proximal lymph nodes, a tissue not examined previously. Potential for
      drainage of vector particles to regional lymph nodes was indicated by experiments
      showing that intramuscular injection of fluorescein-labeled latex beads
      concentrated in the regional lymph nodes in mice. The localization of retroviral
      DNA to the injection site and regional lymph nodes may play a role in the
      induction of the HIV-specific CTL responses detected in splenocyte populations
      isolated from mice 21 days after injection with HIV-IT(V).

PMID- 8867861
TI  - Immune responses to viral antigens versus transgene product in the elimination of
      recombinant adenovirus-infected hepatocytes in vivo.
AB  - Human adenoviruses have been developed as an attractive vehicle for in vivo liver
      directed gene therapy. Problems with the application of first generation
      recombinant adenoviruses to liver-directed gene therapy have been transient
      expression of the recombinant gene and development of hepatitis. Previous studies
      in mouse models of gene transfer to liver and lung suggested that MHC class I
      restricted cytotoxic T lymphocytes (CTLs) to viral antigens may be effectors in
      the elimination of transgene expression. The goal of this study was to evaluate
      the importance of viral antigens versus transgene product in inducing CTL
      mediated hepatocyte destruction in vivo. Immunization of C57BL/6 mice with a lacZ
      expressing adenovirus elicited CTL responses to both viral antigens and the
      transgene product, beta-galactosidase (beta-gal). Adoptive transfer experiments,
      as well as studies involving lacZ-transgenic mice (ROSA-26) revealed that CTLs to
      viral antigens are sufficient to destroy virus-infected hepatocytes, indicating
      that CTLs to beta-gal can not solely account for the observed hepatocyte
      destruction that has characterized the use of first generation viruses. In
      addition, we confirmed that B cell-mediated events do not participate in
      destruction of hepatocytes in vivo, despite the production of virus- and beta-gal
      specific antibodies. These data confirm the hypothesis that viral gene expression
      elicits host responses that contribute to the problem of transgene instability.
      Recombinant adenoviruses must be redesigned to diminish viral gene expression if
      they are to be used in the treatment of chronic diseases.

PMID- 8867862
TI  - Safety and efficacy of in vivo gene transfer into the porcine heart with
      replication-deficient, recombinant adenovirus vectors.
AB  - Gene transfer with replication-deficient recombinant adenovirus (Ad) vectors may
      provide a novel approach to the treatment of some cardiac disorders. The relative
      efficiency of intramyocardial vs intracoronary Ad vector injection in transducing
      myocardial cells remains to be determined. Further, Ad vectors are associated
      with localized inflammation, and this could be associated with clinically
      significant side-effects. Female minipigs underwent open chest surgery and the Ad
      vector AdCMV.NLS beta-gal was injected into the circumflex coronary artery (IC; 2
      x 10(10) p.f.u.; n = 5) or the posterobasal wall of the left ventricle (i.m.; 5 x
      10(9) p.f.u., n = 4; 2 x 10(10) p.f.u., n = 18). The minipigs were killed after 2
      31 days and the hearts examined for evidence of beta-galactosidase activity.
      Minipigs underwent epicardial echocardiography immediately before, within 15 min
      following the i.m. injection of AdCMV.NLS beta-gal and again at the time of
      death. Blood samples for white blood cell count, alkaline phosphatase, total
      bilirubin, blood urea nitrogen, creatinine and electrolytes were obtained before
      i.m. and i.c. injection of the Ad vector and before death. Intramuscular
      injection of the Ad vector was more efficient than i.c. infusion in infecting
      cells in a localized area of the heart. Myocardial beta-gal activity peaked at 3
      6 days after i.m. injection and returned to its control value within 1 month.
      Although inflammatory cells were present at the injection site, echocardiograms
      did not show any evidence of either segmental or global left ventricular
      dysfunction. No minipigs died and all blood tests remained within normal limits
      following either i.m. or i.c. exposure to the Ad vector. In summary, direct i.m.
      administration of replication-deficient, recombinant Ad vectors provides a safe
      and effective approach for short-term gene transfer into the heart of large
      mammals.

PMID- 8867863
TI  - Circumventing the immune response to adenovirus-mediated gene therapy.
AB  - Adenovirus-mediated gene transfer experiments have demonstrated an exceptional
      efficiency of virus uptake and gene expression in a variety of in vivo models.
      Unfortunately, the efficiency of gene delivery is not accompanied by long-term
      gene expression. Maximal gene expression peaks during the first week of infection
      followed by a rapid decline to near baseline levels within several weeks. Data
      from several laboratories implicate host cellular and humoral immune responses as
      being responsible for the limited duration of expression and for the inability to
      successfully readminister a gene using adenovirus vectors. In this study we have
      examined two strategies which, independently or in combination, circumvent
      aspects of the host immune response against adenovirus-mediated gene therapy. The
      first strategy explores induction of immune tolerance in the experimental host as
      a method to increase the duration of gene expression and as a method to allow
      readministration of adenovirus expression vectors. Our second strategy is
      directed at the need to readminister adenoviral vectors to immune competent adult
      animals. We have demonstrated that a sequential exposure of rats to at least two
      other adenovirus serotypes does not compromise our ability to successfully
      administer an Ad5-based CAT expression vector. The characterization of serotype
      specific neutralizing response indicates that the construction and use of Ad
      expression vectors from different serotypes will facilitate a useful adenovirus
      based strategy allowing multiple administrations of a target gene.

PMID- 8867864
TI  - Structural and functional analysis of cationic transfection lipids: the
      hydrophobic domain.
AB  - Cationic lipids (cytofectins) have gained widespread acceptance as pharmaceutical
      polynucleotide delivery agents for both cultured cell and in vivo transfection,
      and the cytofectins DOTAP and DC-Cholesterol are being tested in clinical human
      gene therapy trials. This study reports the effects of modifications in the
      hydrophobic domain of a prototypic cytofectin (DORI), including modifications in
      lipid side-chain length, saturation, and symmetry. A panel of related compounds
      was prepared and analyzed using DNA transfection, electron microscopy, and
      differential scanning calorimetry (DSC). Lipid formulations were prepared with
      dioleoylphosphatidylethanolamine (DOPE) as unsonicated preparations and sonicated
      preparations. Transfection analyses were performed using cultured fibroblasts,
      human bronchial epithelial, and Chinese hamster ovarian cells as well as a mouse
      model for pulmonary gene delivery. In general, cytofectins containing
      dissymmetric hydrophobic domains were found to work as well or better than the
      best symmetric analogs. Optimal side-chain length and symmetry varied with cell
      type. Compounds with phase transitions (Tc) above and below physiological
      temperature (37 degrees C) were tested for DNA transfection activity. In contrast
      to previous reports, cytofectin Tc was not found to be predictive of transfection
      efficacy. Pulmonary treatment with free DNA was found to be at least as effective
      as treatment with commonly used cytofectin:DNA complexes. However, cytofectins
      that incorporate a hydroxyethylammonium moiety in the polar domain were found to
      enhance in vivo gene delivery relative to free DNA.

PMID- 8867865
TI  - Anaerobic bacteria as a delivery system for cancer gene therapy: in vitro
      activation of 5-fluorocytosine by genetically engineered clostridia.
AB  - Certain species of anaerobic bacteria have been shown to localise and germinate
      specifically in the hypoxic regions of tumours, resulting in tumour lysis. We
      propose an innovative approach to cancer gene therapy in which genetically
      engineered anaerobic bacteria of the genus Clostridium are used to achieve tumour
      specific gene delivery. Our strategy involves enzyme/prodrug therapy, in which
      the Escherichia coli enzyme cytosine deaminase is used to convert the non-toxic
      prodrug 5-fluorocytosine to the active chemotherapeutic agent 5-fluorouracil. The
      E. coli gene encoding cytosine deaminase has been cloned into a clostridial
      expression vector and transformed into Clostridium beijerinckii, resulting in
      constitutive expression of cytosine deaminase and significant levels of active
      enzyme in the bacterial medium. When added to an in vitro clonogenic survival
      assay, supernatant from clostridia expressing cytosine deaminase increased the
      sensitivity of murine EMT6 carcinoma cells to 5-fluorocytosine approximately 500
      fold. This high level of prodrug activation, combined with the specificity of
      clostridia for hypoxic regions of tumours, indicates a potential use in cancer
      gene therapy.

PMID- 8867866
TI  - Bone marrow gene transfer in three patients with adenosine deaminase deficiency.
AB  - Adenosine deaminase (ADA) deficiency results in severe combined immune deficiency
      disease (SCID), which is fatal without treatment. Allogeneic bone marrow
      transplantation (BMT) is the treatment of choice if an HLA-identical sibling bone
      marrow donor is available, resulting in almost 100% cure rate. BMT-related
      mortality is high in patients lacking such a donor. For these patients, efficient
      transfer of a recombinant ADA gene into hematopoietic stem cells is a therapeutic
      option if it results in the outgrowth of a 'genetically repaired' lymphoid
      system. Based on successful gene transfer studies in monkeys, we performed
      retrovirus-mediated gene transfer into CD34+ bone marrow cells of three patients
      with ADA deficiency. Two patients received bovine ADA conjugated to polyethylene
      glycol (PEG-ADA); in the third patient, PEG-ADA was started 4 months after gene
      transfer. Gene transfer resulted in a 5-12% transduction frequency of in vitro
      colony forming cells (CFU-Cs). No toxicity was observed during and after infusion
      of the graft. Following infusion of the transduced CD34+ cells, transduced
      granulocytes and mononuclear cells persisted in the circulation for 3 months. In
      addition, the gene was present in the marrow of one of the patients at 6 months
      after gene transfer. Expression of the gene was not detected. After this period,
      the gene could not be detected. In monkey studies we showed that myeloablation,
      which was not performed in the patients, may enhance engraftment of genetically
      modified cells. We hypothesize that lack of myeloablation, administration of
      bovine ADA and low numbers of transduced progenitor cells all may have
      contributed to the relative low numbers of transduced cells in the patients.
      Under these conditions, no selective advantage of the genetically corrected
      progenitor cells was observed.

PMID- 8867867
TI  - Self-administration of the D1 agonist SKF 82958 is mediated by D1, not D2,
      receptors.
AB  - We have previously reported that two D1 dopamine agonists, SKF 82958 and SKF
      77434, are readily self-administered by rats. However, due to the limited
      selectivities of these agents, it was not possible to attribute their reinforcing
      effects exclusively to their D1 actions. To assess the relative involvement of D1
      and D2 receptors in SKF 82958 reinforcement, rats were pretreated 30 min before
      self-administration sessions with either the D1-selective antagonist (+)SCH 23390
      or the D2-selective antagonist raclopride. The D1 antagonist (+)SCH 23390 (5-20
      micrograms/kg, SC) produced significant, dose-related (compensatory) increases in
      SKF 82958; in contrast, the D2 antagonist raclopride (25-400 micrograms/kg, SC)
      did not significantly increase SKF 82958 self-administration, although raclopride
      did increase cocaine self-administration. Compensatory increases in self
      administration rates are thought to reflect antagonist-induced reductions in drug
      reinforcement. Hence, we conclude that SKF 82958 self-administration depends on
      activation of a D1-regulated reinforcement substrate.

PMID- 8867869
TI  - Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite:
      relationship to the CYP2D6 genotype.
AB  - The relationship between the CYP2D6 genotype and the steady state plasma levels
      of nortriptyline (NT), its main active metabolite 10-hydroxynortriptyline (10-OH
      NT) and the NT/10-OH-NT ratio were studied in 21 Caucasian depressed patients
      treated with 100-150 mg NT daily. The patients had participated in a previously
      published study investigating the role of NT and 10-OH-NT for the therapeutic
      effect of NT, and the plasma level data were from that study. In the present
      follow-up study, the patients were genotyped with respect to the polymorphic
      CYP2D6 by allele-specific PCR amplification and EcoRI RFLP. One poor metabolizer
      (PM) was identified and she had the highest plasma concentration of NT. Among the
      20 extensive metabolizers (EM), the genotype (homozygous versus heterozygous EM)
      alone was not found to explain the variance in dose-corrected NT concentrations,
      but contributed significantly when gender was also taken into account. Together,
      these factors accounted for 59% of the variability in NT levels. Female patients
      had higher plasma levels of NT than male patients. 10-OH-NT levels were
      influenced by genotype, and NT/10-OH-NT ratio by genotype and gender. The present
      follow-up study confirms a relationship between the CYP2D6 genotype and the
      plasma levels of NT and its active metabolite. Identification of PM by genotyping
      should be of value for the prediction of the plasma levels and, consequently, the
      lower than average dose of NT required for optimal therapy. Also among EM, the
      genotype contributes to the variability in NT and 10-OH-NT levels but alone is of
      limited practical value for the prediction of optimal dosage.

PMID- 8867868
TI  - Risk factors for orofacial and limbtruncal tardive dyskinesia in older patients:
      a prospective longitudinal study.
AB  - Although there is a consensus that orofacial and limbtruncal subtypes of tardive
      dyskinesia (TD) exist and may represent distinct pathophysiologic entities, few
      studies have examined the incidence of and risk factors associated with the
      development of these TD subtypes. Two hundred and sixty-six middle-aged and
      elderly outpatients with a median duration of 21 days of total lifetime
      neuroleptic exposure at study entry were evaluated at 1- to 3-month intervals.
      Using "mild" dyskinesia in any part of the body for diagnosis of TD, the
      cumulative incidence of orofacial TD was 38.5 and 65.7% after 1 and 2 years,
      respectively, whereas that of limbtruncal TD was 18.6 and 32.6% after 1 and 2
      years. Preclinical dyskinesia was predictive of both orofacial and limbtruncal
      TD. History of alcohol abuse or dependence was a significant predictor of
      orofacial TD only whereas tremor was a significant predictor of limbtruncal TD
      only. Findings support suggestions that orofacial and limbtruncal TD may
      represent specific subsyndromes with different risk factors.

PMID- 8867870
TI  - Clocinnamox antagonism of opioid suppression of schedule-controlled responding in
      rhesus monkeys.
AB  - The antagonist effects of clocinnamox were evaluated against opioid agonists,
      acting at mu, kappa and delta-receptors, in rhesus monkeys (n = 3-4) responding
      under a fixed-ratio 30 (FR 30) schedule for food delivery. Clocinnamox (0.032-0.1
      mg/kg) dose-dependently antagonized fentanyl (0.001-0.32 mg/kg) after either a 3
      h or 1-day pretreatment; there was substantial recovery of agonist potency by 1
      week after clocinnamox. Etonitazene (0.0001-0.01 mg/kg) was also antagonized by
      clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The smaller extent
      of antagonism was not due to the appearance of non mu-opioid response-decreasing
      effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg)
      shifted the etonitazene dose-effect curve in the presence of clocinnamox (0.1
      mg/kg). Clocinnamox (0.1-0.32 mg/kg) did not antagonize the rate-suppressing
      effects of the delta-agonist BW373U86 (0.0.01-1.0 mg/kg) or the kappa-agonist
      U69,593 (0.001-0.032 mg/kg). These results are consistent with previous in vivo
      and in vitro evidence that characterized clocinnamox as an insurmountable
      antagonist, with selectivity for mu- over kappa- and delta-receptors.

PMID- 8867871
TI  - Amphetamine-induced conditioned activity does not result from a failure of rats
      to habituate to novelty.
AB  - Psychostimulant-induced conditioned activity is characterized by the presence of
      a hyperactivity in drug-free rats exposed to an environment previously paired
      with the effects of a psychostimulant. According to the habituation hypothesis,
      conditioned activity arises not through a Pavlovian conditioning process but
      rather because rats under the effects of the psychostimulant would be unable to
      habituate normally to the environment paired with these effects. This hypothesis
      predicts that conditioned activity should not develop in a previously habituated
      environment. This prediction was tested using a within-subject design. In this
      design, conditioned activity is evidenced when a group of rats, following a
      vehicle injection, was more active in a previously amphetamine-paired environment
      than in a previously vehicle-paired environment. The drug-environment pairing
      involved administering rats with d-amphetamine (1.25 mg/kg; SC) immediately prior
      to their placement in one of two distinctive environments. On alternate days, the
      rats received the vehicle and were placed in the other environment. With this
      design, it was found that: a) conditioned activity developed in a previously
      habituated environment; b) its magnitude was independent of the number of
      amphetamine-environment pairings (two, four or eight pairings); c) this
      development of conditioned activity did not result from a forgetting of the
      habituated environment due to a state-dependent retention of the habituation.
      Taken together, these results do not support the habituation hypothesis of
      psychostimulant-induced conditioned activity.

PMID- 8867872
TI  - Evidence that m-chlorophenylpiperazine-induced hyperthermia in rats is mediated
      by stimulation of 5-HT2C receptors.
AB  - Intraperitoneal administration of m-chlorophenylpiperazine (m-CPP) to Wistar rats
      produced hyperthermia with a peak effect at 30 min. Pretreatment with low doses
      of metergoline (5-HT1/5-HT2 antagonist), mesulergine and mianserin (5-HT2C/5-HT2A
      antagonists) blocked m-CPP-induced hyperthermia. Pretreatment with propranolol
      (beta-adrenergic receptor antagonist that also has binding affinity for 5-HT1A, 5
      HT1B and 5-HT2B sites), yohimbine (alpha 2-noradrenergic antagonist that also has
      binding affinity for 5-HT2B sites), MDL-72222 or ondansetron (5-HT3 antagonists)
      did not attenuate m-CPP-induced hyperthermia. Only high doses of ketanserin, LY
      53857 and ritanserin (5-HT2A/5-HT2C antagonists) as well as spiperone (5-HT1A/5
      HT2A/D2 antagonist) attenuated m-CPP-induced hyperthermia. Daily administration
      of m-CPP produced complete tolerance to its hyperthermic effect by day 5.
      However, there was no cross-tolerance to 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI, a 5-HT2A agonist that also has high affinity for 5-HT2C
      receptors)-induced hyperthermia. m-CPP-induced increases in temperature were
      found to be significantly less in the Fawn-Hooded (FH) rat strain as compared to
      the Wistar rat strain; in prior studies, FH rats have been found to be
      subsensitive to other 5-HT2C-mediated pharmacologic responses. Altogether, these
      findings suggest that m-CPP-induced hyperthermia in rats is mediated by selective
      stimulation of 5-HT2C receptors.

PMID- 8867873
TI  - Strain-dependent effects of cocaine on memory storage improvement induced by post
      training physostigmine.
AB  - Post-training administration of the inhibitor of cholinesterase enzymes,
      physostigmine, dose-dependently (0.025-0.4 mg/kg) improved retention of an
      inhibitory avoidance response in C57BL/6 (C57) as well as in DBA/2 (DBA) mice,
      the latter being more responsive than C57 mice. The effects on retention
      performance induced by physostigmine in C57 and DBA mice appeared to be due to an
      effect on memory consolidation. In fact, they were observed when drugs were given
      at short, but not long, periods of time after training, which is when the memory
      trace is susceptible to modulation. Moreover, these effects are not to be
      ascribed to a rewarding or non-specific action of the drugs on retention
      performance, as the latencies during the retention test of those mice that had
      not received a footshock during the training were not affected by the post
      training drug administration. Post-training administration of cocaine (1-5 mg/kg)
      dose-dependently improved retention of an inhibitory avoidance response in C57
      mice, while impairing it in the DBA strain, thus confirming previous results
      (Puglisi-Allegra et al. 1994b). Pretreatment with cocaine at ineffective doses as
      well as at an effective one potentiated the effects of an ineffective as well as
      of an effective dose of physostigmine in C57 mice, while it antagonized the
      effects of the inhibitor of cholinesterase enzymes on memory consolidation in DBA
      mice. The present results indicate that the indirect DA receptor agonist cocaine
      affects physostigmine action on memory consolidation in an opposite manner in the
      two inbred strains, pointing to genotype-dependent interaction between
      cholinergic and dopaminergic activity in memory consolidation.

PMID- 8867874
TI  - Increased 5-HT2C receptor responsiveness occurs on rearing rats in social
      isolation.
AB  - To investigate whether isolation rearing alters 5-hydroxytryptamine2C (5-HT2C)
      receptors, the effect of the serotonin agonist m-chlorophenylpiperazine (mCPP)
      was examined on elevated plus-maze behaviour, plasma corticosterone and brain 5
      HT2C receptor protein levels in rats. There was no distinction between behaviour
      or corticosterone levels in drug-free isolates or socially housed rats exposed to
      the elevated plus-maze. The anxiogenic response to mCPP (decrease in open arm
      entry and time and an increase in stretch attend postures) on the elevated plus
      maze was greater in isolation than in socially reared controls without any
      concomitant difference in the hypolocomotor effect of mCPP in the two groups.
      mCPP produced a greater elevation in plasma corticosterone in isolates than in
      group-housed controls. Hippocampal 5-HT2C receptor protein-like immunoreactive
      levels were significantly lower following mCPP than saline only in rats reared in
      isolation. These results indicate that increased 5-HT2C receptor responsiveness
      accompanies isolation-rearing and may contribute to the enhanced response to
      stress and the increased neophobia seen in this animal model of trait
      anxiety/depression. In isolation reared rats, rapid down-regulation of
      supersensitive 5-HT2C receptors may occur in the hippocampus following 5-HT
      agonist challenge.

PMID- 8867875
TI  - Effect of clonidine on the human acoustic startle reflex.
AB  - The present study investigated in healthy human volunteers whether clonidine
      reduced the amplitude of the acoustic startle reflex and whether this effect, if
      found, was due to an accelerated rate of habituation. Subjects were presented
      with startle-eliciting noise-bursts after intravenous (iv) infusion of clonidine
      (1.5 microgram/kg) and saline on separate days. Clonidine significantly reduced
      the amplitude of the acoustic startle reflex (as indexed by the eyeblink
      component) relative to the saline treated condition. This effect was neither due
      to an accelerated rate of habituation of the startle reflex nor to the sedative
      effect of clonidine. These findings complement an earlier report (Morgan et al.
      1993) that yohimbine augments the amplitude of the startle reflex in man. Taken
      together, the two reports indicate a new model for the clinical investigation of
      central alpha2 adrenoceptor function in humans.

PMID- 8867876
TI  - The effects of a benzodiazepine receptor antagonist beta-carboline ZK-93426 on
      scopolamine-induced impairment on attention, memory and psychomotor skills.
AB  - The effects of a single dose of scopolamine alone and in combination with ZK
      93426 (a beta-carboline antagonist at the GABAA/BZ receptor complex with weak
      inverse agonist activity) were tested in two studies. In one study (study 1) the
      emphasis of enquiry was on different stages of information processing measured by
      a psychometric battery; in the second study (study 2) performance at different
      stages of memory and psychomotor abilities was tested and electroencephalogram
      recordings and video-tracking were also performed. Each study consisted of two
      parts, part I in which scopolamine (0.5 mg; 1 ml) or placebo were administered
      subcutaneously, and part II in which scopolamine (0.5 mg; 1 ml) was administered
      subcutaneously followed by an intravenous injection of ZK 93426 (0.04 mg; 0.04
      ml/kg) or placebo. Thirty-six volunteers, who were randomly allocated to receive
      one of the two treatments (n = 18 per treatment), participated in each part. In
      study 1 attention was measured by a continuous attention task and a rapid
      information processing task, vigilance was measured by a visual vigilance task,
      and working memory and reasoning were evaluated by a logical reasoning task. A
      visual memory task was also included to measure acquisition and retention. In
      study 2 acquisition and short term storage and retrieval were measured by a word
      lists-Buschke restricted reminding procedure, and retention was tested by delayed
      recall and recognition. Psychomotor performance was assessed by measuring tapping
      speed (related to gross motoric abilities) and a pegboard task (related to fine
      motoric abilities). A task to measure working memory, the Pauli test, was also
      included. In study 1 scopolamine significantly impaired performance in the
      attentional and vigilance tasks (P < 0.05), but there was no effect in the
      logical reasoning task main measurements of time and accuracy. In study 2,
      scopolamine also impaired performance in the psychomotor tasks (P < 0.05) and the
      Pauli test. ZK 93426 partially antagonised most of the effects of scopolamine on
      memory and attention, suggesting that an interaction between the GABA-ergic and
      cholinergic systems is reflected in measurements of both attention and memory. In
      general a dissociation was found in the effects of scopolamine on memory, i.e.
      scopolamine impaired performance during all acquisition measurements but left
      retention unaffected.

PMID- 8867877
TI  - Similarity of clozapine's and olanzapine's acute effects on rats' lapping
      behavior.
AB  - As a way of further comparing the behavioral effects of clozapine and olanzapine,
      dose ranges of these drugs were studied in a task emphasizing fine motor detail
      of rats' tongue movements during lapping behavior. Rats lapped drops of tap water
      from a force-sensing disk. From this behavior four variables were derived: peak
      force of tongue strikes, duration of tongue contact, number of separate tongue
      contacts in 2 min, and the rhythm of the lapping behavior as quantified by
      Fourier analysis. Both clozapine (0.5-4.0 mg/kg, IP, 45 min) and olanzapine (0.25
      2.0 mg/kg, IP, 45 min) dose dependently reduced all four measures of behavior.
      With respect to lick rhythm, a behavioral marker which clearly distinguishes
      haloperidol from clozapine in this behavioral paradigm, olanzapine was about
      twice as potent as clozapine, with the two drugs having parallel dose-effect
      functions. Within-session decrements in behavior previously reported for
      haloperidol in the lick task were not produced by clozapine nor by olanzapine.
      Taken together, these data strengthen the idea that the behavioral effects of
      clozapine and olanzapine are strikingly similar, and thereby emphasize the
      potential of olanzapine as an atypical anti-psychotic agent.

PMID- 8867878
TI  - Susceptibility to vinblastine-induced aneuploidy and preferential chromosome
      segregation during meiosis I in Robertsonian heterozygous mice.
AB  - Chromosome segregation at meiosis I was studied in oocytes and spermatocytes of
      four different Robertsonian (Rb) heterozygous mouse stocks by cytogenetic
      analysis of meiotic products. Two Rb heterozygotes spontaneously yielded high
      frequencies of unbalanced oocytes. In one case, Rb(2.18)Rma, the excess
      hyperploidy was mainly accounted for by nondisjunction of normal bivalents,
      suggesting a generalized impairment of meiotic segregation. In each stock,
      frequencies of hyperploid spermatocytes were either not significantly different
      or significantly lower than the corresponding frequencies in the oocytes. This
      confirmed the greater risk of segregational errors in female than in male
      carriers of the same Rb metacentric. The hypothesis that an error prone system of
      meiotic segregation, such as the trivalent configuration of single Rb
      heterozygous oocytes, could be hypersensitive to chemically induced
      malsegregation was tested by injecting Rb heterozygous females with low doses of
      vinblastine (VBL). An intraperitoneal injection of 0.06 or 0.09 mg/kg VBL before
      the first meiotic division significantly increased the spontaneous frequency of
      hyperploid oocytes, inducing segregational errors of both the trivalent and
      normal bivalents. The comparison of these data with VBL effects in B6C3F1 mice
      showed that single Rb heterozygous oocytes are more sensitive to VBL-induced
      meiotic aneuploidy than oocytes with a standard karyotype. Although segregation
      distortion has been repeatedly shown in the progeny of Rb heterozygous mice with
      a significant excess of all telocentric balanced offspring, it has never been
      demonstrated whether this is a primary event occurring during meiotic segregation
      or a consequence of selective postconceptional death. In this study, we showed
      that preferential segregation occurred during female meiosis in all the Rb stocks
      tested. When segregation distortion was analyzed separately in balanced and
      unbalanced oocytes, the latter did not show preferential segregation, suggesting
      that, when the two telocentrics segregated from each other, then the metacentric
      was randomly directed to the ovum or the polar body.

PMID- 8867879
TI  - Cellular and subcellular localization of transforming growth factor-alpha and
      epidermal growth factor receptor in normal and diseased human and hamster
      pancreas.
AB  - Four normal pancreas, 8 chronic pancreatitis specimens, and 30 non-endocrine
      pancreatic tumors from humans and 6 normal and 6 induced pancreatic cancers in
      hamsters were examined immunohistochemically by antibodies against human
      transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor
      (EGFR). Two normal pancreas and two pancreatic cancer specimens from each species
      were also studied immunoelectron microscopically by the immunogold method. In
      chronic pancreatitis, the reactivity and intensity of the staining with both
      antibodies were much greater in ductal/ductular cells than in the normal
      pancreas. All 30 pancreatic cancers reacted with both antibodies with a variable
      degree of reactivity and staining intensity. No correlation was found between the
      histological type of tumors, the degree of tumor differentiation, and the
      incidence and patterns of reactivity of either antibody. Immunoelectron
      microscopically, both EGFR and TGF-alpha were demonstrated primarily on the basal
      membrane. In the normal hamster pancreas, TGF-alpha was overexpressed in the
      alpha-cells but not in any other islet cells. Both TGF-alpha and EGFR were
      marginally detectable in the exocrine pancreas and in induced pancreatic lesions.
      This is the first demonstration of subcellular localization of TGF-alpha and EGFR
      in the normal and diseased human and hamster pancreas.

PMID- 8867881
TI  - Mouse embryonic development and tumor cell growth under the influence of
      recombinant trichosanthin (a ribosome inactivating protein) and its muteins.
AB  - Trichosanthin, a ribosome inactivating protein, is known to possess embryotoxic
      and antiproliferative activities. In the present study recombinant trichosanthin
      and its muteins produced by site-directed mutagenesis were tested for these
      activities using whole embryo culture and cell culture. The results revealed that
      when Glu 160 in trichosanthin was mutated to alanine or aspartate, the two
      aforementioned activities underwent a substantial decrease. However, the former
      mutein had a higher potency than the latter mutein. When both Glu 160 and Glu 189
      were mutated, the resultant mutant possessed very low antiproliferative and yet
      considerable embryotoxic activity, indicating the contribution from other amino
      acids in stabilizing the transition state complex of trichosanthin.

PMID- 8867880
TI  - Lack of promoting activity of four pesticides on induction of preneoplastic liver
      cell foci in rats.
AB  - Four pesticides were examined for hepatopromoting activity using a medium-term
      bioassay based upon induction of glutathione S-transferase placental form (GST-P)
      positive foci in the rat liver. Male F344 rats were initially injected with
      diethylnitrosamine (DEN; 200 mg/kg body weight) intraperitoneally and 2 weeks
      later were treated with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN; 75
      and 150 ppm), diazinon (500 and 1,000 ppm), phenthoate (500 and 1,000 ppm), or
      iprobenfos (500 and 1,000 ppm) in the diet for 6 weeks and then killed, all rats
      being subjected to partial hepatectomy at week 3. All of the pesticides gave
      negative results, the numbers and areas of GST-P positive foci not exceeding the
      control values for animals given DEN alone. Indeed, a significant reduction of
      foci development was seen for EPN (75 ppm). These findings provide experimental
      evidence that the presently examined four pesticides do not have
      hepatocarcinogenic potential in rats.

PMID- 8867882
TI  - Standardized medical decisions.

PMID- 8867883
TI  - The practice parameter initiative.

PMID- 8867884
TI  - Practice guideline development task force of the College of American
      Pathologists. Hereditary hemochromatosis.
AB  - Hereditary hemochromatosis is an autosomal recessive disorder, the gene for which
      occurs in approximately 10% of Americans, most of whom are unaffected
      heterozygotes. Approximately 5/1000 white Americans are homozygous and at risk of
      developing severe and potentially lethal hemochromatosis. The disorder affects
      numerous organ systems, but the most common symptoms are fatigue, palpitations,
      joint pains, and impotence; the most common signs are those that relate to
      hypothalamic, cardiac, hepatic or pancreatic dysfunction, including poor cold
      tolerance, impotence in males, amenorrhea in females, cardiac arrhythmias,
      dyspnea, edema, hepatosplenomegaly, spider telangiectases, ascites, deformity,
      swelling or limitation of motion of joints, weight loss, hyperpigmentation.
      Characteristic abnormalities of laboratory tests include elevated serum iron
      concentration, high transferrin saturation, elevated serum ferritin
      concentration, elevated serum transaminases, hyperglycemia and low values for
      thyroid-stimulating hormone (TSH) and gonadotropins. Death may be the result of
      cardiac arrhythmia, congestive heart failure, liver failure or liver cancer.
      Since many of these complications cannot be reversed once they have developed,
      early diagnosis and treatment are essential. In view of the high prevalence in
      the American population (prevalence varies with ethnic background), the low cost
      of diagnosis and treatment, the efficacy of treatment if begun early, and, on the
      other hand, high costs and low success rate of late diagnosis and treatment,
      systematic screening for hemochromatosis is warranted for all persons over the
      age of 20 years. The initial screening should be by measurement of serum iron
      concentration and transferrin saturation. The practice guideline provides a
      diagnostic algorithm for cases in which the serum transferrin saturation is 60%
      or greater. It also provides guidelines for clinical management.

PMID- 8867885
TI  - Degradation of glycated hemoglobin by erythrocytic proteolytic enzymes.

PMID- 8867886
TI  - Prevalence of biotin-binding immunoglobulin in patients with allergic and
      autoimmune diseases.

PMID- 8867887
TI  - Properties and units in the clinical laboratory sciences. I. Syntax and semantic
      rules IUPAC--IFCC recommendations 1995.
AB  - This document is an updating of previous recommendations on the presentation of
      properties and their values in clinical laboratory sciences from IFCC, IUPAC and
      WHO. It forms part of the ongoing effort towards 'standardization' of
      transmission of laboratory requests and reports across cultural/language domains
      while avoiding standardization of the language used by clinicians or laboratory
      practitioners. Subsequent documents will list the kinds-of-property and the
      properties used in clinical laboratory sciences.

PMID- 8867888
TI  - Properties and units in the clinical laboratory sciences. V. Properties and units
      in thrombosis and haemostasis: ISTH-IUPAC-IFCC recommendations 1995.
AB  - For historical reasons, the terms used in the nomenclature for properties in
      thrombosis and haemostasis differ according to 'school' of thought. This hampers
      communication. In collaboration, The Scientific and Standardization Committee of
      the International Society on Thrombosis and Haemostasis and the Committee
      (Commission) of Quantities and Units (in Clinical Chemistry) have prepared a set
      of recommended systematic names for properties in that domain. For use in
      electronic transmission each property has been given a code value.

PMID- 8867889
TI  - Correlation of the OSR/ZRCI gene product and the intracellular glutathione levels
      in Saccharomyces cerevisiae.
AB  - The OSR (oxidative-stress-resistance) gene was cloned as the gene which enhances
      resistance against oxidative stress caused by lipid hydroperoxide in
      Saccharomyces cerevisiae. The nucleotide sequence of the gene was determined and
      found to be identical with the zinc-resistance-conferring (ZRCI) gene, which was
      cloned as the gene enhancing the resistance against zinc and cadmium. A knockout
      mutant of the OSR gene showed increased sensitivity to lipid hydroperoxide. The
      intracellular glutathione content in the knockout mutant decreased approx. 40%
      compared with that of wild-type cells, whereas it increased 3-fold in yeast
      overexpressing the OSR gene. Therefore the OSR/ZRCI gene product seems to
      regulate the intracellular glutathione content.

PMID- 8867890
TI  - Pattern of growth and respiratory activity of Saccharomyces cerevisiae (baker's
      yeast) cells growing entrapped in an insolubilized gelatin gel.
AB  - Yeast cells immobilized by entrapment in an insolubilized gelatin gel have been
      investigated with regard to their pattern of growth and respiratory activity.
      Mass-transfer resistance offered by the matrix and growth of the entrapped cells
      determine a gradient of nutrients throughout the gel which is responsible for
      both a lower specific growth rate of immobilized cells with respect to that of
      free ones, and a heterogeneous biomass distribution, with progressively increased
      cellular density from the inside to the outside of the matrix. The spatial
      organization of the growing cells leads to the formation of a biofilm perfectly
      adherent to the surface of the matrix. Measurements of the oxygen-uptake rate of
      the immobilized cells, after having been released from the matrix by trypsin
      digestion, and confocal microscopy of cells stained with Rhodamine 123
      demonstrate the occurrence of a gradient of respiratory activity throughout the
      immobilized culture.

PMID- 8867891
TI  - Effect of heterogeneity of hydrophobic moieties on surface activity of lichenysin
      A, a lipopeptide biosurfactant from Bacillus licheniformis BAS50.
AB  - Lichenysin A, a surface-active lipopeptide produced by Bacillus licheniformis,
      strain BAS50, contains longchain beta-hydroxy fatty acids. Regulation of the
      synthesis of fatty acids and beta-hydroxy fatty acids was studied by modifying
      the culture medium. Addition of branched-chain alpha-amino acids to the medium
      caused similar changes to both cellular fatty acid and to beta-hydroxy fatty acid
      composition in the lipophilic part of lichenysin A. Production of lichenysin A
      was enhanced about two- and four-fold by addition of L-glutamic acid and L
      asparagine respectively. It is suggested that these amino acids may be involved
      in the control of lipopeptide formation. Elucidation of the structure-function
      relationship of surface-active lipopeptides by analysis of the activities of
      structurally characterized compounds is discussed. Fractions of lichenysin A with
      branched beta-hydroxy acids in the lipid tail demonstrated lower surface-tension
      activity than the fractions of lichenysin A having straight beta-hydroxy acids.
      The presence of a lichenysin A fraction with beta-hydroxymyristic [(C14)n] acid
      residues appears to have an important influence on the surface activity of a
      mixture of lichenysins A.

PMID- 8867892
TI  - Strain-dependent variation in the NADH-dependent diacetyl reductase activities of
      larger- and alebrewing yeasts.
AB  - Significant differences were observed in the zymogram patterns of NAD(+)
      dependent ethanol dehydrogenase and acetoin dehydrogenase activity in seven
      strains of brewer's yeast examined by non-denaturing PAGE. Bottom-fermenting
      (lager) strains contained quite different activity bands of acetoin dehydrogenase
      activity compared with top-fermenting (ale) strains. These differences were
      confirmed when cell-free extracts of ale yeasts were heated at 55 degrees C. This
      destroyed most of the diacetyl reductase activity, while leaving acetaldehyde
      reductase and other reductase activities unaffected. In contrast, heating cell
      free extracts of lager yeasts at 55 degrees C inactivated diacetyl reductase
      activity and the other reductase activities at the same rate, and more slowly
      than with ale strains. Similar distinctions between the two types of yeast could
      be made by examining the effect of heat on the ratio (activity of the various
      substrates with NADH as electron donor)/(activity with reduced acetylpyridine
      adenine dinucleotide as electron donor). The data show that the acetoin
      dehydrogenase/diacetyl reductase enzyme present in ale-yeast strains differs in
      mobility and heat-stability from that of larger strains, and that both can be
      distinguished from the major alcohol dehydrogenase activity bands.

PMID- 8867893
TI  - Biochemical characterization of the recombinant Boophilus microplus Bm86 antigen
      expressed by transformed Pichia pastoris cells.
AB  - In the present paper we report the biochemical characteristics of the recombinant
      tick (Boophilus microplus) gut antigen Bm86 that previously has been cloned,
      expressed and recovered at high levels in the methylotrophic yeast Pichia
      pastoris. The results demonstrate that rBm86 had a modification at position 92
      (Thr replaced by Ile) and aggregated, forming particles ranging between 17 and 40
      nm. The rBm86 was N-glycosylated, having at least two non-glycosylated sequons
      (Asn-329 and Asn-363) and a ratio of only 0.4/65 (free Cys/total Cys)/mol of
      protein.

PMID- 8867894
TI  - Enhanced biological activity of human recombinant interleukin 2 coupled to mouse
      red blood cells as evaluated using the mouse Meth A sarcoma model.
AB  - In order to circumvent the toxicity associated with high-dose interleukin 2 (IL2)
      administration and its rapid clearance from the circulation, a carrier system for
      IL2 is needed. Red blood cells (RBCs) coated with recombinant interleukin 2
      (rIL2) provide a means of delivering IL2 into the system in a continuous low-dose
      manner which, in turn, maintains a low, potentially non-toxic, IL2 concentration.
      Murine RBCs coated with rIL2 (RBCs-rIL2) are able to induce cytotoxic activity in
      mouse spleen cells in vitro against malignant murine YAC-1 cells (53-62%
      cytotoxicity) using less than 4500 i.u./10(9) RBCs per mouse. Cytotoxicity (21
      31%) becomes apparent upon cytotoxic testing of spleens cells stimulated in vivo.
      Using the murine Meth A sarcoma model, the effectiveness of this RBC-rIL2 vehicle
      is demonstrated in vivo by a 84% reduction in tumour size as compared with the
      soluble-rIL2-treated mice. Moreover, the RBC-rIL2 vehicle is able to induce
      tumoricidal cytotoxicity with very low rIL2 concentrations (about 10,000 i.u. of
      rIL2/mouse). These results indicate that rIL2 retains its biological activity
      when bound to the RBC and therefore could prove useful as a therapeutic delivery
      system for cancer treatment.

PMID- 8867895
TI  - Expression in Escherichia coli of thermostable elongation factor 1 alpha from the
      archaeon Sulfolobus solfataricus.
AB  - The elongation factor 1 alpha from the archaeon Sulfolobus solfataricus (SsEF-1
      alpha) was expressed in Escherichia coli and purified. The SsEF-1 alpha gene was
      amplified by PCR and cloned in the Ndel site of the pT7-7 expression vector,
      under the control of the promoter of T7 RNA polymerase. Upon induction with
      isopropyl beta-D-thiogalactopyranoside, the recombinant SsEF-1 alpha (recSsEF-1
      alpha) was purified from the E. coli S-100 extract by a two-step procedure. From
      1 litre of cell culture, about 2 mg of purified recSsEF-1 alpha was obtained. The
      N-terminal sequence of the first 30 amino acid residues of recSsEF-1 alpha was
      identical with that translated from the nucleotide sequence of the corresponding
      gene, except for the initial residue, which in recSsEF-1 alpha was Ser instead of
      Met. The M(r) of recSsEF-1 alpha (determined by electrospray MS) was almost
      coincident with that of the naturally occurring SsEF-1 alpha (SsEF-1 alpha). The
      thermal-inactivation and thermophilicity profiles of SsEF-1 alpha and recSsEF-1
      alpha were identical. Concerning the functional properties, recSsEF-1 alpha was
      able to support poly(Phe) synthesis in vitro, to bind GDP and GTP and to elicit
      an NaCl-dependent GTPase activity [Masullo, De Vendittis and Bocchini (1994) J.
      Biol. Chem. 269, 20376-20379] with the same efficiency as that displayed by SsEF
      1 alpha.

PMID- 8867896
TI  - Purification and characterization of NADH oxidase from the archaea Sulfolobus
      acidocaldarius and Sulfolobus solfataricus.
AB  - The enzyme NADH oxidase (EC 1.6.99.3) has been isolated from the two
      thermoacidophilic archaea Sulfolobus acidocaldarius and Sulfolobus solfataricus
      and characterized. In both organisms the enzyme oxidizes specifically beta-NADH
      in the presence of molecular oxygen and requires the presence of a flavin
      cofactor, showing a high specificity for FAD. A stoicheiometric amount of
      hydrogen peroxide to NADH is formed as the end product of the reaction,
      indicating that both enzymes are two-electron donors. The purified enzymes
      exhibit quite different molecular properties. S. acidocaldarius NADH oxidase is a
      monomeric protein with an estimated molecular mass of about 27 kDa, whereas S.
      solfataricus NADH oxidase is a dimeric protein with a molecular mass of 35 kDa
      per subunit; S. solfataricus NADH oxidase is purified as an FAD-containing
      protein, whereas S. acidocaldarius NADH oxidase does not contain a flavin
      molecule. Furthermore, a comparison of the N-terminal amino acid sequence shows
      no similarities either between the two proteins or to any other NADH oxidases.
      Both enzymes are essentially thermophilic. In the temperature range 20-80 degrees
      C, the energy of activation is almost the same for both activities, suggesting
      that similar energetic parameters are required. Also both oxidases display a
      great stability to heat. The half-life of heat inactivation is about 180 min at
      90 degrees C for S. acidocaldarius NADH oxidase and 77 min at 98 degrees C for
      the S. solfataricus enzyme. The activity of the two enzymes is inhibited by urea
      and guanidine and are regulated very differently by several organic solvents.

PMID- 8867897
TI  - Antiplatelet agents affecting the interaction of Tissue Factor-Factor VIIa
      complex with Factor X in a continuous-flow reactor.
AB  - The purpose of the present study was to examine the role of antithrombotic agents
      in the activation of Factor X in the presence of the Tissue Factor-Factor VIIa
      (TF-VIIa) complex in a continuous-flow reactor. Tissue Factor immobilized in a
      phospholipid bilayer on the inner surface of a capillary tube (internal diameter
      = 0.27 mm) was exposed to a perfusate containing Factors VIIa and X flowing at a
      flow rate of 12.7 microliters/min, corresponding to a wall shear rate of 100 s-1.
      Factor Xa (the activated form of Factor X) in the effluent was determined by a
      chromogenic assay. The effectiveness of two platelet aggregation inhibitors,
      alpha,alpha'-bis-[3-(N,N-diethylcarbamoyl)piperidino-p-xylene dihydrobromide (A
      1) and alpha,alpha'-bis-[3-N-benzyl-N-methylcarbamoyl)piperidino]-p-xylen e
      dihydrobromide (A-4) in inhibiting Factor X activation is reported here. The
      results suggest that the Tissue Factor pathway, mediated through TF-VIIa complex,
      produces significantly lower levels of Factor Xa in the presence of compounds A-1
      and A-4. On the basis of these findings, it appears that the anticoagulation
      action of these compounds reinforces their platelet aggregation-inhibitory
      properties. These carbamoylpiperidines (nipecotamides) therefore appear to be
      useful antithrombotic agents.

PMID- 8867898
TI  - Production and characterization of biologically active Ala-Ser-(His)6-Ile-Glu-Gly
      Arg-human prolactin (tag-hPRL) secreted in the periplasmic space of Escherichia
      coli.
AB  - Human prolactin (hPRL) cDNA was obtained by screening of a pituitary cDNA library
      with a synthetic 21-mer oligonucleotide and with rat PRL cDNA. For its
      expression, use was made of a vector, p3SN8, containing tac-promoter-controlled
      sequences for a bacterial cellulase leader joined to sequences coding for Ala
      Ser, a chromatographic affinity site consisting of six histidines and a Factor Xa
      cleavage site. The hPRL cDNA was inserted at the 3' end of the cleavage-site
      sequences. Expression in Escherichia coli led to secretion in the periplasmic
      space of a fully bioactive hPRL variant constituting authentic hPRL with a
      peptide tag, i.e. Ala-Ser-(His)6-Ile-Glu-Gly-Arg, at its N-terminal. This tag
      hPRL could be rapidly and efficiently purified by metal-chelate affinity
      chromatography. The correct processing and quality of tag-hPRL was monitored by
      SDS/PAGE, Western-blot analysis, immunoassay and Nb2-lymphoma-cell bioassay.
      Treatment with Factor Xa for tag removal was only partially successful.
      Periplasmic secretion of tag-hPRL of the order of 0.7 micrograms/ml per A600 unit
      and one-step purification indicate feasibility for tag-hPRL production for in
      vitro diagnostic and research applications. This is the first report describing
      periplasmic secretion of a bioactive form of hPRL.

PMID- 8867899
TI  - Purification of a lipase from Acinetobacter calcoaceticus AAC323-1 by hydrophobic
      interaction methods.
AB  - The performance of hydrophobic-interaction chromatography (HIC) for the
      purification of Acinetobacter calcoaceticus AAC323-1 lipase was compared with
      that of various aqueous two-phase systems. While a 42% lipase yield with a
      purification factor of 140 could be recovered by HIC, higher yields were achieved
      by using aqueous two-phase systems, either those formed by poly(ethylene glycol)
      and dextran or those based upon the use of a detergent. Triton X-114-based
      aqueous two-phase partition showed the best performance, with a yield of 81% and
      a purification factor of 68. Further detergent removal was easily achieved with
      an adsorbent, with no significant decrease in yields. Owing to its simplicity,
      the method should be easy to scale-up.

PMID- 8867900
TI  - Status and transcriptional activity of a bovine-papillomavirus-I-based expression
      vector in a recombinant production cell line.
AB  - We have analysed the status and transcriptional activity of the bovine
      papillomavirus-I (complete BPV-I genome)-based expression vector pCES in CI27i
      cell-line-derived 3TI cells used for the industrial production of recombinant
      human erythropoietin (rhuEpo). Complete tandem head-to-tail integration of about
      600 vector copies at a single site of the cellular genome was observed.
      Deletions, insertions or rearrangements of pCES-specific sequences or
      extrachromosomal copies of vector sequences were not detected. Transcriptional
      analyses demonstrated that rhuEpo was abundantly expressed. BPV-I early
      transcription was detected, as expected from a BPV-I-transformed cell line;
      however, compared with the mouse metallothionein-I-promoter-driven rhuEpo
      specific transcription, it was very weak. Late BPV-I transcription was also not
      detected in 3TI cells under conditions of large-scale rhuEpo production.
      Therefore this expression system proved to be safe and suitable for the
      production of rhuEpo.

PMID- 8867901
TI  - Analogies between oxytocin systems of the uterus and brain.
AB  - In this brief review we have compared OT systems in the brain with those of the
      uterus and ovary particularly with respect to interactions with steroids. We have
      presented evidence of heterogeneous OTR and 125I-P-3-BSA binding sites in the
      MPOA as well as evidence of extensive interactions of steroids and OT in the
      MPOA, that cannot be adequately explained by genomic effects of steroids. We also
      discuss a putative analogue between steroid control of OTR stimulation of
      intracellular calcium levels, phospholipase C activity and prostaglandins in the
      uterus and steroid effects on OT systems in brain. We have developed a model for
      steroid control of both OT release and OTR in which we suggest that steroids and
      OT bind to membrane receptors coupled to G proteins. This model may prove useful
      in understanding the interactive central actions of steroids and OT systems in
      regulating the endocrinology and behaviors associated with reproduction.

PMID- 8867902
TI  - Muscle contractile activity modulates GLUT4 protein content in the absence of
      insulin.
AB  - We examined whether muscle contractile activity directly modulates GLUT4 protein
      content in rat skeletal muscle without the participation of insulin action or via
      amplified insulin action. To attain this purpose, the effects of increased, by
      training, or eliminated, by denervation, muscle contractile activity on muscle
      GLUT4 protein concentration were investigated in severely insulin-deficient
      diabetic rats. For the first set of experiments, insulin-deficient diabetic rats
      (induced by injection of 80 mg/kg B.W. streptozotocin) were trained for three
      weeks by treadmill running (90 min/day, 19 m/min, 10%, 6 days/week). GLUT4
      protein concentration in soleus muscle was increased by 48% (p < 0.01) as
      compared with diabetic sedentary animals. For the second set of experiments, rats
      were injected with streptozotocin (100 mg/kg). The muscles innervated by the
      sciatic nerve of one leg were denervated four days after injection of
      streptozotocin. Three days after denervation, soleus muscles in both legs were
      excised. Insulin deficiency decreased GLUT4 protein concentration in innervated
      soleus muscle. In insulin-deficient diabetic rats, denervation also decreased
      soleus GLUT4 protein concentration by 50% (p < 0.01) as compared with the
      contralateral innervated muscle. Furthermore, the effects of insulin-deficiency
      and denervation on GLUT4 protein concentration were additive. These results
      provide evidence that muscle contractile activity directly modulates skeletal
      muscle GLUT4 protein concentration independent of insulin action.

PMID- 8867903
TI  - Influence of postnatal overnutrition and pregnancy on non-insulin dependent
      diabetes induced in Wistar rats by neonatal streptozotocin.
AB  - Wistar rats with non-insulin dependent diabetes induced by neonatal
      streptozotocin (STZ) administration were raised either in large or in small
      litters. The STZ-treated rats from small litters showed a higher body weight as
      well as increased blood glucose levels compared with vehicle- and STZ-treated
      rats reared in large nests at an age of 8 weeks. The higher body weight of these
      rats was maintained until an age of 15 weeks, whereas the basal blood glucose was
      normalized. However, both STZ-treated groups exhibited an impaired glucose
      tolerance. During pregnancy only the glucose tolerance of the STZ-treated animals
      from large nests was improved although not normalized. The STZ-treated rats from
      small nests failed to adapt to pregnancy because the blood glucose levels after
      glucose load were similar to values found in the virgin state. The body weight of
      pregnant STZ treated rats raised in small litters was significantly lower than in
      vehicle- or STZ-terated rats from large nests. The number of fetuses per litter
      was similar in all groups tested. Compared with the vehicle-treated rats from
      large litters the fetal body weight of STZ-treated rats from small nests was
      decreased and that of STZ rats raised in large litters was increased. These
      results suggest that the rats with the more impaired glucose tolerance produce
      growth-retarded pups and, conversely, rats with rather mild impairment have
      bigger fetuses than the vehicle-treated ones. In the present study we have
      examined for the first time the combined effects of postnatal overnutrition and
      pregnancy on glucose homeostasis of rats treated neonatally with STZ. Our data
      demonstrate that postnatal overnutrition is an aggravating factor in the
      development of a diabetic state in these rats, especially at times when the
      insulin requirement is higher such as puberty and pregnancy.

PMID- 8867904
TI  - Combined therapy with insulin and sulfonylurea for the treatment of new-onset
      insulin-dependent diabetes mellitus.
AB  - The progressive B-cell destruction at the onset of type 1 diabetes and the
      relevance of residual B-cell function to metabolic control prompted us to try to
      prevent further B-cell destruction in new-onset type 1 diabetic patients. Having
      already shown positive effects of sulfonylreas in long-standing IDDM patients, we
      decided to try the association of gliclazide with insulin in newly diagnosed IDDM
      patients. Therefore, 22 patients were randomly assigned to either gliclazide, 160
      mg/24 h, or placebo (in association with standard insulin treatment) from the
      third week since the onset of the disease. Patients were studied every 6 months
      for 18 months. The insulin need was similar in the two groups at time 0, but
      thereafter it steadily decreased in the GCZ group becoming at 6, 12 and 18
      months, respectively 65%, 42% and 39% of that of the PL group. The metabolic
      control was very similar in the two groups throughout the study. The residual B
      cell function (fasting and post-breakfast C peptide), which was similar in the
      two groups at time 0, remained unchanged or improved in the GCZ group, whereas it
      decreased in the PL group. In conclusion, the combined insulin-gliclazide
      treatment appeared to improve B-cell function during the first 18 months of type
      1 diabetes, inducing a major reduction of the insulin need with respect to
      patients treated with insulin alone.

PMID- 8867905
TI  - Therapeutic effect of glibenclamide in a fixed combination with metformin or
      phenformin in NIDDM patients.
AB  - The combination of a sulfonylurea with a biguanide improves the pancreatic beta
      cell insulin secretion and the insulin utilization in peripheral tissues in
      NIDDM. This open, crossover, randomised and prospective study was designed to
      compare the effects of the fixed combination glibenclamide-metformin (GL-METF)
      2.5 and 400 mg respectively, with the fixed combination glibenclamide-phenformin
      (GL-PHEN)-2.5 and 25 mg respectively, on NIDDM diabetes control. Thirty NIDDM
      patients, in ideal metabolic control, who were being treated with GL-PHEN were
      divided in two groups. One group received GL-PHEN for 12 weeks followed by 12
      weeks treatment with GL-METF and the reverse treatment was given to the second
      group. A statistically significant decrease of post-prandial blood glucose (p =
      0.034) and glycosylated haemo-globin (p < 0.02) values was observed under GL-METF
      treatment compared to those with GL-PHEN. The values of lactic acid were within
      normal limits during both treatments. The insulin secretion after breakfast was
      similar with both drug compounds. The BMI of the patients remained the same
      during a follow-up study of 24 weeks. Lipid metabolism did not change
      significantly during the trial and the safety parameters (renal and liver
      function, full blood count) remained unchanged. In conclusion, the administration
      of GL-METF leads to better diabetes control in NIDDM patients compared to that of
      GL-PHEN.

PMID- 8867906
TI  - Platelet aggregation in type 1 diabetes without microvascular disease during
      continuous subcutaneous insulin infusion.
AB  - The effect of metabolic control on platelet activities was studied in eleven
      insulin-dependent diabetic patients during six months of continuous insulin
      infusion (CSII) treatment in comparison to three months of conventional therapy.
      Diabetic patients chosen for the study were free of microvascular disease.
      Glycemia control was improved during CSII treatment and a significant hemoglobin
      A1c reduction from 8.26 +/- 1.78 to 6.16 +/- 0.46%, p < 0.001, was achieved. The
      accompanying improvement in platelet aggregation in response to two agonists was
      only observed with the achievement of glycemia control (ADP: 20.84 +/- 4.61 vs
      14.84 +/- 3.03%, p < 0.001; arachidonic acid: 22.04 +/- 4.26 vs 16.0 +/- 3.15%, p
      < 0.01). The synthesis of proaggregatory thromboxane B2, as a response to
      arachidonate, was lower during the CSII period (TxB2: 415 +/- 51 vs 382 +/- 36
      micrograms/l.10(6) platelets), but with no statistical significance. Inspite of
      the fact that in all patients, lipoprotein concentrations were of normal values
      both before and after intensified therapy (HDL-c: 1.48 +/- 0.5 vs 1.52 +/- 0.4
      mmol/l, NS; LDL-c: 3.2 +/- 1.3 vs 2.7 +/- 1.0 mmol/l, NS), a significant
      correlation was observed between the atherogenic lipoprotein fraction and
      aggregation parameters. Thus, in all patients, LDL-cholesterol before and during
      CSII showed a significant correlation with platelet sensitivity to ADP (r = 0.61,
      p < 0.002), whereas at the same time its correlation with the corresponding
      values of HDL-cholesterol (r = -0.52, p < 0.01) was negative. Our results
      suggested that intensive insulin treatment reduced platelet aggregation in
      patients without microvascular disease when strict glycemia control was
      maintained and indicated that changes in platelet aggregation could directly
      result from changes in plasma glucose concentrations.

PMID- 8867907
TI  - Potentiating effect of galanin on GHRH-induced GH release. Comparison between old
      and young subjects.
AB  - The aim of our study was to investigate the effect of galanin on basal and GHRH
      stimulated GH secretion in a healthy group of elderly subjects and in a healthy
      group of young subjects for comparison. Ten old subjects (mean age 75 +/- 1.15
      years) and an equal number of healthy young volunteers (mean age 26 +/- 0.71
      years) underwent three stimulation tests in random order. Galanin infusion for 60
      minutes (10 micrograms/kg in 100 ml saline) failed to provoke an appreciable
      release of circulating GH in old subjects, while it induced a significant
      increase of plasma GH in the young adults; GHRH administration i.v. in bolus (100
      micrograms in 1 ml saline) elicited a significant GH response in both groups;
      however, in the older group GH response was significantly (p < 0.05) lower than
      in the young adults. The administration of galanin (10 micrograms/kg in 100 ml
      saline as an i.v. infusion for 60 min) plus GHRH (100 micrograms in 1 ml saline
      i.v. in bolus), potentiated GH response in old and young subjects. The combined
      administration of two peptides was able to elicit a clear GH release even in the
      older subjects who were hyporesponsive/unresponsive to galanin and/or GHRH alone.
      In the elderly, plasma GH values observed after the combined stimuli overlapped
      with GH values observed after GHRH alone in the young adults. In conclusion, our
      study confirms that galanin has a synergic effect with GHRH on GH release both in
      younger and elderly subjects. Moreover, our data confirm an impaired responsivity
      to GHRH in the elderly and demonstrate that galanin is able to normalize response
      of somatotrophs to GHRH in old people.

PMID- 8867908
TI  - Intermittent Cushing's disease in hirsute women.
AB  - Clinical symptoms of Cushing's syndrome were recognized in approximately 23 of 97
      successive hirsute women attending the Endocrinological Department of the Women's
      Hospital. Endocrine and radiological examinations ultimately confirmed Cushing's
      syndrome caused by pituitary microadenomas (Cushing's disease) in only 2 women.
      In 17 of the remaining 21 patients suspected of having Cushing's disease
      hypercortisolism could not be diagnosed by classical endocrine tests. Thus
      further endocrinologial tests as corticotrophin releasing hormone (CRH)-tests
      (100 micrograms i.v.) and insulin tolerance tests were initiated including serum
      and stress-free salivary cortisol profiles during the day. Diurnal cortisol
      profiles showed higher values in the morning than during the night, but
      intermittent elevated cortisol concentrations could be detected. Finally, seven
      patients could be classified as suffering from a special form of pituitary ACTH
      dependent hypercortisolism, named intermittent Cushing's disease (ICD). It is
      characterized by severe Cushingoid symptoms like marked central adiposity, purple
      striae, hirsutism and acne, intermittently increased cortisol concentrations, no
      cortisol response to hypoglycaemia, but preservation of some diurnal variation of
      serum or saliva cortisol. Three of these seven patients had diagnostic
      transsphenoidal neurosurgery and pituitary ACTH-producing microadenomas were
      removed in two women. Repeated determinations of the circadian rhythm of cortisol
      in saliva samples in combination with an overnight 1 mg dexamethasone suppression
      and an insulin stimulation test, are recommended to diagnose patients with
      suspicion on ICD even in an outpatient clinic.

PMID- 8867909
TI  - The hydrolysis of parathyroid hormone by papain-solubilized rat meprin differs
      from that of detergent-solubilized meprin.

PMID- 8867910
TI  - Effect of glucocorticoids on the secretion of growth hormone in man.

PMID- 8867911
TI  - Primary adrenal lymphoma presenting as Addisonian crisis. Pitfalls in the
      diagnosis of bilateral adrenal swelling.

PMID- 8867912
TI  - Nicotine attenuates naloxone-induced jumping behaviour in morphine-dependent
      mice.
AB  - In the present study the effect of nicotine on naloxone-induced jumping behaviour
      in morphine-dependent mice was examined. In addition, the modulatory role of
      dopaminergic, adrenergic and cholinergic mechanisms upon the effect of nicotine
      were investigated. Animals were rendered dependent on morphine by subcutaneous
      (s.c.) injections of morphine sulfate 3 times a day for 3 days, and jumping
      behaviour was induced by intraperitoneal (i.p.) administration of naloxone 2 h
      after the tenth injection of morphine sulfate on day 4. Nicotine (0.001-2 mg/kg
      s.c.) caused a significant decrease in withdrawal jumping behaviour in morphine
      dependent mice. The effect of nicotine was blocked by the central nicotinic
      antagonist mecamylamine (0.01-0.1 mg/kg i.p.) but not by the peripheral nicotinic
      antagonist hexamethonium (0.01 and 0.1 mg/kg i.p.) nor the muscarinic receptor
      antagonist atropine (2.5-10 mg/kg i.p.). The dopamine receptor antagonist SCH
      23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3-benzazepine-7-ol
      maleate) (0.01-0.5 mg/kg s.c.) reduced the response induced by nicotine. The
      dopamine receptor antagonist sulpiride (25 and 50 mg/kg s.c.) and the
      adrenoceptor antagonists phenoxybenzamine (5 and 10 mg/kg i.p.) and propranolol
      (5 and 10 mg/kg i.p.) were without an effect. The results indicate that the
      effect of nicotine on naloxone-induced jumping is mediated by central nicotinic
      receptors.

PMID- 8867913
TI  - Behavioural evidence for cholecystokinin-dopamine D1 receptor interactions in the
      rat.
AB  - The effects of cholecystokinin (CCK) on behavioural responses to the dopamine D1
      receptor agonist (+/- )SKF 38393 ((+/- )-2,3,4,5-tetrahydro-7,8- dihydroxy-1
      phenyl-1H-3-benzazepine HCl) were studied in the rat. SKF 38393 (5 mg/kg s.c.)
      induced stereotyped grooming and vacuous chewing movements. Both responses were
      inhibited by CCK-8S (10-50 micrograms/kg i.p.), but the preferential CCKB
      receptor agonist CCK-4 (20-100 micrograms/kg i.p.) attenuated SKF 38393-induced
      grooming only. Suppression of SKF 38393-induced grooming and vacuous chewing
      movements by CCK-8S was blocked by the selective CCKA receptor antagonist MK-329
      (also known as devazepide or L-364,718) (0.1, 0.3 mg/kg i.p.) but unaffected by
      the CCKB receptor antagonist L-365,260 (0.1, 0.3 mg/kg i.p.). We conclude that
      CCK can modify dopamine-mediated behavioural responses, possibly reflecting an
      action post-synaptic to dopamine terminals. The effect on dopamine D1 receptor
      agonist-induced vacuous chewing movements is probably mediated by CCKA receptors,
      while the effect on grooming may reflect an interaction with the CCKA receptor
      and/or a novel CCKB receptor subtype.

PMID- 8867914
TI  - 'Quality of life' after therapy in rats with myocardial infarction: dissociation
      between hemodynamic and behavioral improvement.
AB  - Rats with myocardial infarction provide a clinically relevant model for
      hemodynamic and survival studies. Moreover, behavioral changes in this model,
      i.e. increased anxiety and reduced interest in environment and social
      interactions, mimic aspects of the reduced quality of life of patients. In the
      present study, we investigated whether pharmacological treatment that is known to
      improve hemodynamics and prognosis could also affect the behavioral changes
      associated with quality of life. Rats with 3-week-old infarcts were treated with
      intermittent dobutamine (1 mg/kg i.p., twice daily) or captopril (2 milligrams in
      drinking water). After 2 weeks of treatment, when from previous studies
      hemodynamics are expected to be restored, behavioral tests were performed. In the
      free exploration test, which primarily evaluates exploratory behavior, dobutamine
      normalized the reduced interest in the environment. In the standard open field
      and social interaction tests, which also include an anxiety component, the
      beneficial effects of dobutamine were not observed. In contrast, captopril
      normalized all behavioral changes that indicated increased anxiety. In
      conclusion, the expected similar hemodynamic improvement with dobutamine and
      captopril treatment resulted in improvement of different aspects of the changed
      behavior of rats with myocardial infarction, indicating that there is no direct
      relationship between hemodynamics and quality of life. The behavioral tests used,
      in combination with our previously described functional hemodynamic measurements,
      could provide a new basis for evaluating the effects of therapy on hemodynamic
      function as well as the quality of life.

PMID- 8867915
TI  - Modulatory effect of agents active in the presynaptic dopaminergic system on the
      striatal dopamine transporter.
AB  - We have investigated the effects of agents active in the presynaptic dopaminergic
      system on the characterization of the rat striatal dopamine transporter. The
      dopamine transporter was characterized by high-affinity [3H]GBR 12935 (1-[2
      diphenylmethoxy)-ethyl]-4-(3-phenylpropyl)-piperazine) binding to a membrane
      preparation and by [3H]dopamine uptake into striatal synaptosomes. Subchronic
      treatment with reserpine (2.5 mg/kg, 4 days), a monoamine depletor, caused a
      significant decrease in both [3H]GBR 12935 binding (20%) and [3H]dopamine uptake
      (51%). In contrast, amantadine (a dopamine releaser) treatment (20 mg/kg, 21
      days) induced an increase (28%) in the maximal number of [3H]GBR 12935 sites.
      Chronic levo-dopa (dopamine precursor) treatment combined with carbidopa (50
      mg/kg and 5 mg/kg respectively, 21 days) as well as benztropine (dopamine uptake
      inhibitor) treatment (10 mg/kg, 21 days) did not affect the striatal dopamine
      transporter characteristics. The present results showed that the striatal
      dopamine transporter is sensitive to changes in dopaminergic neurotransmission
      caused by agents that do not interact directly with the dopamine carrier.

PMID- 8867917
TI  - Amphiphilic alpha-tocopherol analogues as inhibitors of brain lipid peroxidation.
AB  - Neurological disorders, such as stroke, trauma, tardive dyskinesia, Alzheimer's
      and Parkinson's diseases, may be partially attributed to excessive exposition of
      the nervous tissue to oxygen-derived radicals. A novel water-soluble alpha
      tocopherol analogue, 2,3-dihydro-2,2,4,6,7-pentamethyl-3-(4-methylpiperazino)
      methyl-1-benzofuran-5-ol dihydrochloride (MDL), is a potent radical scavenger.
      Following subcutaneous administration to mice, MDL inhibited the lipid
      peroxidation induced in the 100-fold diluted brain homogenates, with an ID50 of 8
      mg/kg. Rapid brain penetration, within 30-60 min postadministration, and even
      distribution into different brain areas were observed. MDL was also detected
      after oral administration. In brain homogenate undergoing lipid peroxidation, MDL
      prevented the consumption of an equal amount of alpha-tocopherol, while
      inhibiting the concomitant malondialdehyde formation. The radical scavenging
      capacity of MDL was superior to that of alpha-tocopherol, although the peak and
      half-peak potentials were not significantly different. However, MDL was much less
      lipophilic, the partition coefficient (log P) at the octanol/water interface
      being 1.91. Although it is yet unknown, whether the applied criteria sufficiently
      predict its usefulness, beneficial effects of MDL may be expected in the above
      mentioned disorders.

PMID- 8867916
TI  - Naloxonazine antagonism of levorphanol-induced antinociception and respiratory
      depression in rhesus monkeys.
AB  - The mu-opioid receptor antagonist effects of naloxonazine on levorphanol-induced
      thermal antinociception and respiratory depression were examined in rhesus
      monkeys. Levorphanol (0.032-3.2 mg/kg) produced dose-dependent increases in tail
      withdrawal latencies from 50 degrees C water in a warm-water tail-withdrawal
      assay and dose-dependent decreases in ventilation in both air and 5% CO2 mixed in
      air. Naloxonazine (0.1-3.0 mg/kg) antagonized both the antinociceptive and
      ventilatory effects of levorphanol to a similar degree, and the antagonist
      effects of naloxonazine were greater after 1 h than after 24 h. Under all
      conditions, the antagonist effects of naloxonazine were fully surmountable.
      Schild analysis of the antagonist effects of naloxonazine after 1 h pretreatment
      in the antinociception assay yielded a pA2 value of 7.6 and a slope of -0.50; by
      comparison, quadazocine yielded a pA2 value of 7.5 and a slope of -1.05. These
      results suggest that naloxonazine acts as a potent and fully reversible mu-opioid
      receptor antagonist with a moderately long duration of action in rhesus monkeys.
      In addition, these results suggest that the antinociceptive and ventilatory
      effects of mu-opioid receptor agonists in rhesus monkeys are mediated by
      pharmacologically similar populations of mu opioid receptors.

PMID- 8867918
TI  - Synergy between mu/delta-opioid receptors mediates adenosine release from spinal
      cord synaptosomes.
AB  - Morphine releases adenosine from the spinal cord and this contributes to spinal
      antinociception. The present study examined possible interactions between mu- and
      subclasses of delta-opioid receptors in the release of adenosine. Nanomolar (10(
      8), 10(-9) M) concentrations of morphine release adenosine from spinal cord
      synaptosomes under conditions of partial depolarization with elevated K+, and
      this component of release is mediated by activation of mu-opioid receptors.
      Subnanomolar (10(-10), 10(-11) M) concentrations of the mu-opioid receptor
      agonists morphine, [N-MePhe3,D-Pro4]morphiceptin, and [D-Ala2,N-Me-Phe4,Gly5
      ol]enkephalin (DAMGO) have minimal effects on the release of adenosine from the
      spinal cord. However, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta 1-opioid
      receptor agonist, and [D-Ala2,Cys4]deltorphin, a delta 2-opioid receptor agonist,
      at doses which exhibit no intrinsic effects (10(-8) and 10(-7) M), shifted the
      dose-response curve for mu-opioid receptor-evoked adenosine release to the left
      in a dose-dependent manner. DPDPE was more potent than [D-Ala2,Cys4]deltorphin
      when combined with the highly selective mu-opioid receptor agonist [N-MePhe3,D
      Pro4]morphiceptin, but these agents showed similar activity with the less
      selective agonists DAMGO and morphine. Simultaneous activation of mu- and delta
      opioid receptors generates a synergistic release of adenosine from spinal cord
      synaptosomes. Although agonists for both delta 1- and delta 2-opioid receptor
      subtypes produce this response, the delta 1-opioid receptor agonist is more
      potent at eliciting this effect when the most selective mu-opioid receptor ligand
      is used.

PMID- 8867919
TI  - Blockade of the polyamine site of NMDA receptors produces antinociception and
      enhances the effect of morphine, in mice.
AB  - The possible effect of ifenprodil--a potent antagonist at the polyamine site of
      the NMDA receptor complex--on nociceptive threshold and morphine analgesia was
      investigated in mice. In the hot plate test, the intraperitoneal (i.p.) injection
      of ifenprodil significantly prolonged the reaction time of mice at the dose of 30
      mg/kg, and increased the analgesic effect of morphine. In the phenylquinone
      writhing test, ifenprodil reduced the number of abdominal constrictions of mice
      starting from the dose of 2.5 mg/kg i.p., and increased the effect of morphine.
      The effect of ifenprodil on pain threshold was prevented by naloxone. Moreover,
      ifenprodil antagonized the pain threshold-reducing effect of alpha-melanocyte
      stimulating hormone (0.05 microgram/mouse, intracerebroventricularly). These data
      show that blockade of the polyamine site of the NMDA receptor complex produces
      analgesia and increases the analgesic effect of morphine.

PMID- 8867920
TI  - Effects of NK433, a new centrally acting muscle relaxant, on masticatory muscle
      reflexes in rats.
AB  - The effects of (-)-(R)-2-methyl-3-(1-pyrrolidinyl)-4'-
      trifluoromethylpropiophenone monohydrochloride (NK433), a novel centrally acting
      muscle relaxant, on masticatory muscle reflexes were investigated in rats. NK433
      inhibited the monosynaptic tonic vibration reflex of the masseter muscle and the
      polysynaptic tonic periodontal masseteric reflex. These reflexes are increased by
      gamma-motor activity. NK433 had a weak inhibitory effect on the polysynaptic jaw
      opening reflex evoked by electrical stimulation of the tooth pulp, which is
      little related with gamma-motor activity. Eperisone-HCl depressed the three types
      of masticatory muscle reflexes. When intravenously administered, eperisone-HCl
      was equipotent to NK433, but the effect of eperisone-HCl was shorter-lasting than
      that of NK433. The effect of intragastrically administered NK433 on the
      periodontal masseteric reflex was about three times stronger than that of
      eperisone-HCl. These results suggest that NK433 inhibits masticatory muscle
      reflexes controlled by the gamma-motor system and thus may ameliorate the
      temporomandibular joint syndrome in man.

PMID- 8867921
TI  - Cytosolic Ca2+ domain-dependent protective action of adenosine in cardiomyocytes.
AB  - Recently, in beating cardiac cells heterogeneous spatiotemporal patterns in
      cytosolic Ca2+ distribution have been visualized, and associated with cell
      contraction. In non-beating cardiomyocytes, spatial heterogeneity of
      intracellular Ca2+ distribution has also been observed, yet its functional
      implication in resting cardiac cells is not known. Herein, distinct domains of
      lower versus higher concentrations of cytosolic Ca2+ (0.17 and 0.37 microM,
      respectively) were observed using epifluorescent digital imaging in single, non
      beating, fluo-3-loaded cardiomyocytes. Extracellular K+ (16 mM) induced a uniform
      increase of cytosolic Ca2+, despite the initial presence of distinct domains of
      cytosolic Ca2+ (from 0.17 to 1.82 microM in domains with lower, and from 0.37 to
      2.03 microM in domains with higher Ca2+ concentration, respectively). In
      contrast, adenosine (1 mM) prevented exracellular K+ to induce cytosolic Ca2+
      loading selectively within domains with lower (from 0.17 to 0.18 microM), but not
      in domains with higher (from 0.37 to 1.4 microM) basal Ca2+ concentration. Thus,
      the response of a cardiomyocyte to the protective action of adenosine is
      heterogeneous within a resting single cell. The domain-distinct cytoprotective
      action of adenosine appears to be set by the basal Ca2+ concentration within a
      cytosolic domain.

PMID- 8867922
TI  - Down-regulation of benzodiazepine receptors by ethyl beta-carboline-3-carboxylate
      in cerebrocortical neurons.
AB  - Effect of exposure of primary cultured cerebral cortical neurons to ethyl beta
      carboline-3-carboxylate (beta-CCE) on the function of benzodiazepine receptors
      was studied. Exposure of neurons to beta-CCE (0.1-10 microM) decreased the
      binding of [3H]flunitrazepam to extensively washed membrane fractions in a dose-
      and time-dependent manner, whereas the binding of [3H]flunitrazepam to the
      cytosolic fractions increased (180%) under the same conditions as described
      above. Ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a] [1,4]
      benzodiazepine-3-carboxylate (Ro15-1788), an antagonist of the central type of
      benzodiazepine receptors, completely abolished the beta-CCE-induced decrease in
      [3H]flunitrazepam binding and the IC50 value for [3H]flunitrazepam binding to the
      extensively washed membrane fractions prepared from beta-CCE-treated neurons was
      similar to that from non-treated neurons. Scatchard analysis revealed that only
      the Bmax value for [3H]flunitrazepam binding decreased after the exposure to beta
      CCE (1 microM) for 12 h, although the Kd value was not altered. These results
      indicate that beta-CCE induces the down-regulation of benzodiazepine receptors by
      an increase in benzodiazepine receptor internalization.

PMID- 8867923
TI  - Pregnenolone sulfate increases intracellular Ca2+ levels in a pituitary cell
      line.
AB  - We have investigated the rapid steroid effects on intracellular calcium ([Ca2+]i
      levels in a clonal pituitary cell line (GH3). Among the steroids tested only
      pregnenolone sulfate induced a rapid and transient [Ca2+]i increase within 1 min.
      The specificity of pregnenolone sulfate-induced [Ca2+]i increase with respect to
      steroid structure was pronounced. Other steroids (5-40 microM) including
      pregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate,
      progesterone, estradiol-17 beta, testosterone, 5 alpha-dihydrotestosterone, 5
      alpha-dihydrotestosterone, 5 alpha-dihydroprogesterone, and 3 alpha,5 alpha
      tetrahydroprogesterone were found to be ineffective. The [Ca2+]i increase with
      pregnenolone sulfate (30 microM) was completely abolished in a Ca(2+)-free medium
      or in the presence of La3+ (0.1 mM) and Co2+ (5 mM). The organic Ca2+ channel
      blockers methoxyverapamil (100 microM) and nicardipine (5 microM) both showed
      similar inhibitions (> 73%). The interaction between pregnenolone sulfate and
      voltage-gated Ca2+ channels (VGCC) was shown by coapplication of pregnenolone
      sulfate (10 microM) with Bay K 8644 (0.1 mM) or KCl (15 mM). Coapplication of
      pregnenolone sulfate with KCl increased the [Ca2+]i in an additive manner.
      However, with the specific agonist Bay K 8644(+/-), the pregnenolone sulfate
      effect was potentiated in a majority of the cells, suggesting cooperative
      interaction between the two. The results demonstrate that pregnenolone sulfate
      induces a rapid Ca2+ influx in GH3 cells. The marked nicardipine block also
      suggests that most of the Ca2+ influx is mediated through L-type VGCC.

PMID- 8867924
TI  - Comparison of tBuBHQ with chemotactic peptide and phorbol ester in O2- production
      in HL-60 cells.
AB  - The effect of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a Ca2+ pump
      inhibitor, on superoxide anion (O2-) production was examined with a special
      reference to Ca2+ in HL-60 cells differentiated by dibutyryl cAMP, and compared
      with the effect of N-formyl-Met-Leu-Phe (fMLP) and phorbol 12-myristate 13
      acetate (PMA). tBuBHQ caused O2- production and Ca2+ mobilization, but not
      phosphoinositide hydrolysis. fMLP caused O2- production, Ca2+ mobilization and
      phosphoinositide hydrolysis. PMA caused O2- production without affecting Ca2+
      mobilization and phosphoinositide hydrolysis. EGTA and O,O'-bis(2
      aminophenyl)ethyleneglycol- N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester
      (BAPTA/AM), an intracellular Ca2+ chelator, inhibited O2- production induced by
      fMLP, but not by tBuBHQ. Thapsigargin, another Ca2+ pump inhibitor, had a weak
      ability to produce O2-. fMLP, but not tBuBHQ, caused BAPTA/AM-sensitive
      activation of phospholipase A2 and D. tBuBHQ caused O2- production by interacting
      with phosphatidylcholine in a cell-free system. The results suggest that tBuBHQ
      causes O2- production independent of Ca2+, and Ca2+ might be a cofactor in the
      activation of phospholipase A2 and D upstream in fMLP-induced O2- production.

PMID- 8867926
TI  - [Lower esophageal sphincter function in gastroesophageal reflux].

PMID- 8867925
TI  - Dual effects of oxidized low-density lipoprotein on immune-stimulated nitric
      oxide and prostaglandin release in macrophages.
AB  - Oxidized low-density lipoprotein (LDL) is currently regarded as a tentative key
      player in atherosclerosis by virtue of its ability to induce intracellular lipid
      accumulation and to modulate cell functions in the vessel wall. We previously
      demonstrated that inducible nitric oxide (NO) synthase activity is attenuated in
      lipid-laden J774 macrophages obtained by incubation with oxidized LDL 200
      micrograms ml-1 for 24 h. In the present study we investigated the effect of
      oxidized LDL in a lower concentration (20 micrograms ml-1) or for a shorter time
      (6 h) and the possible mediator role of prostaglandin E2 and prostacyclin.
      Prostaglandins and the NO synthase metabolites citrulline and nitrite were
      elevated in the 24 h supernatant after immune stimulation with interferon-gamma
      100 U ml-1 with or without lipopolysaccharide 10 micrograms ml-1. Pretreatment
      with oxidized LDL 20 micrograms ml-1 for 18 h decreased nitrite release by 31 +/-
      2%, whereas prostaglandin production was not affected. A 6 h pre-exposure to 200
      micrograms ml-1 had an opposite effect: it significantly potentiated interferon
      gamma-stimulated prostaglandin E2 (10-fold), prostacyclin (7-fold), nitrite (1.5
      fold), and citrulline (2.4-fold) release. Indomethacin 10 microM abolished the
      prostaglandin production and largely prevented the oxidized LDL-dependent
      increase in NO synthase activity. Acetylated LDL was without effect. The data
      show that the immune-induced release of NO is potentiated or suppressed,
      depending on the conditions of exposure to oxidized LDL. The potentiation due to
      short, high-dose exposure is partly mediated by prostaglandins since indomethacin
      inhibited both processes.

PMID- 8867927
TI  - [Function of the esophagus and stomach in gastroesophageal reflux].

PMID- 8867928
TI  - [Problem with myotomy in laparoscopic surgery for esophageal achalasia base on
      observation from esophageal radiography and esophageal pressure].

PMID- 8867929
TI  - [Strain gauge measurement of digestive tract motility in gastric tube
      reconstruction].

PMID- 8867930
TI  - [Gastric emptying of radiopaque markers].

PMID- 8867931
TI  - [Significance of gastric antrum contraction in liquid meal emptying. An
      ultrasonographic evaluation].

PMID- 8867932
TI  - [Gastric antral and duodenal pressure measurement in 24 hours in Hirschsprung
      disease].

PMID- 8867934
TI  - [Gastric reflux of taurocholic acid in peptic ulcer: symptoms and drug therapy].

PMID- 8867933
TI  - [Effect of octreotide on gastric and duodenal motility].

PMID- 8867935
TI  - [An experimental study on the esophageal sphincter and pylorus motility during
      vomiting].

PMID- 8867936
TI  - [Duodenal gastric reflux and duodenal motility].

PMID- 8867937
TI  - [Gastric emptying and small intestinal transport in chronic pancreatic
      insufficiency].

PMID- 8867938
TI  - [Quality of life and digestive tract function examination: double tract method].

PMID- 8867939
TI  - [Gastric secretion and motility function after pylorus-preserving
      pancreaticoduodenectomy].

PMID- 8867941
TI  - [ATP-induced electric current in rat aortic smooth muscle cells].

PMID- 8867940
TI  - A study of pyloric function after pylorus-preserving pancreatoduodenectomy in the
      canine model.

PMID- 8867942
TI  - [Influence of sarcoplasmic reticulum Ca-ATPase inhibition on carotid artery
      smooth muscle in stroke-prone spontaneously hypertensive rats and Wistar Kyoto
      rats].

PMID- 8867943
TI  - Intracellular Ca2+ oscillations in vascular smooth muscle cells.
AB  - We monitored caffeine- and histamine-induced [Ca2+]i oscillations by patch-clamp
      whole-cell recordings of K(Ca)-current in single smooth muscle cells of rabbit
      cerebral (basilar) artery. Superfusion of caffeine (1 mM) or histamine (1-3
      microM) induced periodic oscillations of large whole-cell K-current with fairly
      uniform amplitudes and intervals. Repetitive activations of the large-conductance
      K(Ca)-channels were recorded in the cell-attached patch mode. Inclusion of
      heparin (3 mg/ml) in the pipette solution failed to inhibit the oscillations
      caused by caffeine treatment, but blocked histamine-evoked oscillations.
      Ryanodine (1-10 microM) abolished both caffeine- and histamine-induced
      oscillations. Removal of extracellular Ca2+, but not verapamil or Cd2+, abolished
      the caffeine-induced oscillations, and the changes in the oscillatory frequency
      closely reflected the altered Ca2+ influx rate. These results indicate that in
      smooth muscle cells of the rabbit cerebral artery, ryanodine-sensitive Ca(2+)
      induced Ca2+ release (CICR) pools play key roles for the generation of the
      [Ca2+]i oscillations.

PMID- 8867944
TI  - [Endothelium-dependent hyperpolarization of coronary smooth muscle in rabbits and
      guinea pigs].

PMID- 8867945
TI  - [Effect of aging on alpha-1 receptor-mediated, phenylephrine-induced contraction
      and pressor response: relationship with the amount of receptors].

PMID- 8867946
TI  - Neural responses of rat abdominal skin artery.

PMID- 8867947
TI  - [Effect of cholestyramine on angiopathies in cholesterol-fed mice and diabetic
      mice].

PMID- 8867948
TI  - [Modulation of A-type calcium independent transient outward potassium current by
      fatty acids in guinea pig single smooth muscle cell].

PMID- 8867949
TI  - [Contractile dysfunction and alteration of PKC activity in gastric smooth muscle
      of diabetic rats].

PMID- 8867950
TI  - [Two types of non-selective cation channel current in guinea pig taenia caeci
      smooth muscle cells].

PMID- 8867951
TI  - Effects of purinergic agonists on mechanical and electrical activities of gastric
      smooth muscle of guinea-pig.
AB  - The effects of purinergic agonists on the mechanical and electrical activity of
      antral circular muscle of guinea-pig stomach were investigated. ATP potentiated
      the mechanical contraction without any change in membrane potential. To
      characterize the purinoceptors involved, effects of ATP analogues, especially P2X
      or P2Y receptor agonists, were studied. 2-MethylthioATP (2-MeSATP), a P2Y
      agonist, showed the same effects as that of ATP. On the other hand, a P2X
      agonists, alpha, beta-methyleneATP (alpha, beta-MeATP) incuced relaxation with
      hyperpolarization. At the holding potential of 0 mV, spontaneous transient
      outward currents (STOCs) were recorded in whole-cell mode. Externally applied ATP
      revealed transient increase of STOCs. Considering that STOCs reflect the changes
      of internal Ca2+, these results might be explained by the transient increase of
      internal Ca2+ release from internal Ca2+ store. From these results, it is
      concluded that there are at least two types of purinoceptors in guinea-pig
      stomach, and contractile response via P2Y-purinoceptor might be related to the
      elevation of internal Ca2+ released from internal Ca2+ store.

PMID- 8867952
TI  - Effect of intracellular cAMP on K current in single gastric myocytes of guinea
      pig.
AB  - In guinea-pig stomach, the effect of increased intracellular cAMP induced by
      forskolin, 8-Br-cAMP, or isobuthyl-methylxanthine (IBMX) on K current was studied
      in whole-cell currents. In enzymatically dispersed single cells, agents elevating
      [cAMP]in showed quite different effects on the IK depending on the recording
      conditions. Though using the same recording pipette containing 0.1 mM EGTA,
      agents elevating [cAMP]in reduced IK(Ca) recorded at various membrane potentials,
      while forskolin increased the spontaneous transient outward currents (STOCs)
      recorded at fixed holding potential, 0 mV. Such a reduction of K currents was not
      observed in the cells dialysed with heparin contained in the recording pipette.
      These results suggested the possibility that the cAMP modulate the internal
      Ca(2+)-store. To assess the effect of cAMP on the internal Ca2+ store, carbachol
      or caffeine was used to mobilize intracellular Ca2+ store. Using the carbachol-
      or caffeine-induced IK(Ca), the effects of forskolin on [Ca2+]in was
      investigated. Forskolin inhibited the carbachol-induced K current, while the
      caffeine-induced current was not affected. From the above results, it might be
      suggested that increased intracellular cAMP might modulate the release of Ca2+
      from IP3-sensitive Ca2+ store to- reduce the Ca(2+)-activated K currents.

PMID- 8867953
TI  - [Relationship between Oddi's sphincter and contraction of duodenum].

PMID- 8867954
TI  - [Extrahepatic bile duct movement and bile excretion during vomiting in dogs].

PMID- 8867955
TI  - [Postprandial gallbladder contraction and the role of CCK receptors in conscious
      dogs].

PMID- 8867956
TI  - [Study of pancreatic duct pressure in the biliary tract and pancreatic diseases:
      endoscopic pressure determination of the pancreatic duct].

PMID- 8867957
TI  - [Equal power electrogastrography].

PMID- 8867958
TI  - [Clinical application of 24 hour Holter electrogastrography in diabetic autonomic
      neuropathy patients].

PMID- 8867959
TI  - [Postprandial changes in percutaneous electrogastrography].

PMID- 8867960
TI  - [Responses to different test meal loading in percutaneous electrogastrography in
      children].

PMID- 8867961
TI  - [Comparison of preoperative and postoperative electrogastrography on digestive
      tract motility in cholelithiasis].

PMID- 8867962
TI  - [Effect of lipopolysaccharide on nitric oxide synthase family (neural NOS,
      endothelial NOS and inducible NOS)].

PMID- 8867963
TI  - [Effect of carboxy-PTIO (NO scavenger) on rabbit vascular smooth muscle].

PMID- 8867964
TI  - Synthetic N omega-hydroxy-L-arginine causes endothelium-dependent vascular
      relaxation both in vitro and in vivo.

PMID- 8867965
TI  - [Endothelium-dependent relaxation response to cyclopiazonic acid in rat
      mesenteric arterial bed].

PMID- 8867966
TI  - [Role of gastric vascular smooth muscle cells in the pathogenesis of stress
      ulcer].

PMID- 8867967
TI  - [Relationship between distal colonic motility and nitric oxide in anesthetized
      rats].

PMID- 8867968
TI  - [Structure of esophageal Auerbach's plexus and distribution of nitric oxide
      neurons in guinea pigs].

PMID- 8867969
TI  - [Nitric oxide donors and endogenous nitric oxide induced relaxation in isolated
      rat duodenum].

PMID- 8867970
TI  - [Nitric oxide nerve distribution in the human intestines].

PMID- 8867971
TI  - Effects of nitric oxide on canine gastrointestinal motility.

PMID- 8867972
TI  - [Nitric oxide-related substance and cyclic GMP non-dependent relaxation in rat
      colon].

PMID- 8867973
TI  - [NANC relaxation and potassium channel in rat colon and rectum].

PMID- 8867974
TI  - [Cyclic GMP and relaxation of rat colonic smooth muscle].

PMID- 8867975
TI  - [Non-adrenergic-non-cholinergic relaxation and nitric oxide in the intestines of
      Hirschsprung disease].

PMID- 8867976
TI  - Hypoxic contraction of isolated rat pulmonary artery.
AB  - The effects of hypoxia in precontracted rat pulmonary artery rings with and
      without endothelium was studied. Hypoxia (30 mmHg) produced a contraction
      (hypoxic pulmonary vasoconstriction, HPV). Removal of endothelium abolished the
      HPV. The HPV was reproducible. The amplitude of HPV was similar to arteries
      equilibrated with 100% O2 and room air. L-NNA markedly inhibited the HPV whereas
      indomethacin was ineffective. HPV was inhibited by caffeine, but not inhibited by
      nifedipine. It would be concluded that HPV in isolated rat pulmonary arteries is
      dependent on the endothelium and the mechanisms involved may be inhibition of
      basal NO production.

PMID- 8867977
TI  - [Pre-synaptic M2 receptor and ET receptor in tracheal smooth muscle].

PMID- 8867978
TI  - [Prostaglandin E2-induced contraction and membrane potential change in bronchial
      smooth muscle].

PMID- 8867979
TI  - [Tracheal smooth muscle dilation effect by anticholinergic agent in chronic
      pulmonary emphysema].

PMID- 8867980
TI  - [Mechanism of morphological changes of platelets upon exposure to cold].

PMID- 8867981
TI  - [Serotonin's relaxation effect on the circular muscle of guinea pig stomach
      fundus].

PMID- 8867982
TI  - [Effect of exogenous serotonin on guinea pig gastric circular muscle strips].

PMID- 8867983
TI  - [The role of endogenous serotonin in interdigestive gastric contraction].

PMID- 8867984
TI  - [Mechanism of increased gastric motility effect of EM523].

PMID- 8867985
TI  - [Erythromycin derivative EM574 with motilin agonistic effect on human gastric
      antrum].

PMID- 8867986
TI  - [Phase III contraction inhibition and gastric acidification in Pavlov and
      Heidenhain pouch in dogs].

PMID- 8867987
TI  - [Motilin-induced phase III contraction and the role of vagus nerve in gastric
      acidified dogs].

PMID- 8867988
TI  - [Effect of peptide YY and the role of vagus nerve in gastric secretion and
      motility in conscious dogs].

PMID- 8867989
TI  - [Effect of KW5139 during early postoperative period after denervation].

PMID- 8867990
TI  - [W-type ileal pouch pressure and transcutaneous electrical activity in relations
      to clinical defecation scores].

PMID- 8867991
TI  - [Peptidergic nerve distribution in the gallbladder in cholelithiasis].

PMID- 8867992
TI  - Effects of various stimulants on intracellular free calcium concentration of
      longitudinal muscle cells isolated from pregnant rat myometrium.

PMID- 8867993
TI  - Repetition of oxytocin stimuli increases the sensitivity of oxytocin receptors in
      the dissected myometrium.

PMID- 8867994
TI  - [Strain gauge force transducer measurement of uterine contraction in conscious
      non-pregnant dogs].

PMID- 8867995
TI  - Stochastic model of receptor-mediated cytomechanics and dynamic morphology of
      leukocytes.
AB  - The proposed mathematical model investigates the simplified cytomechanics of cell
      shape change driven by stochastic stimulation from chemosensory receptors. The
      cytomechanical component of our model describes the dynamical distribution of F
      actin and associated forces in an idealized cortical actin network around the
      cell periphery. The chemosensory component describes the distribution of
      chemotactic receptors in the cell membrane surrounding the cortex, where bound
      receptors give rise to an intracellular signal which modulates some property of
      the cortical network. As in our earlier models, an account is made for (1) the
      reactive, contractive properties of cortical actin, but here also for a stress
      induced by curvature of the cortex-membrane complex which carries an effective
      surface tension, and (2) statistical fluctuations in receptor binding, but
      generalized here to include statistical fluctuations in the spatial distribution
      of receptors, entirely determined by the additional prescription of membrane
      diffusion coefficients along with total receptor number, receptor binding rate
      constants and the local concentration field of chemotactic factor. We simplify
      the analysis by restricting the model to a prototype in which viscous stresses in
      the cortical network are negligible and the radial extension of the cell cortex
      is a prescribed function of the cortical actin concentration. We assume in
      particular that the assembly rate of cortical actin depends on the local density
      of bound receptors. These assumptions lead to a 4th-order parabolic differential
      equation on the unit circle coupled to a system of stochastic differential
      equations. We characterize via bifurcation analysis, stochastic simulations, and
      analytical correlation functions the spatial-temporal pattern of cell morphology
      under the influence of fluctuations in the bound receptor distribution for the
      case of a uniform concentration field of chemotactic factor. In addition to
      addressing the biological significance of our model, we remark on its relevance
      to the generic problem of the influence of correlated stochastic perturbations on
      spatial patterns in morphogenetic media.

PMID- 8867996
TI  - Enantioselective binding of Casodex to the androgen receptor.
AB  - 1. The biologic activity of androgens is mediated through the formation of a non
      covalent androgen receptor (AR)-steroid complex. Casodex and other antiandrogens
      inhibit formation of this complex and thus negate the role of endogenous steroids
      in androgen-dependent growth of prostate. 2. Casodex is currently available as a
      racemic mixture. The goal of this investigation was to determine the in vitro AR
      binding affinities of the individual isomers of Casodex. 3. The (R) or (S)
      isomers of Casodex were synthesized according to the general synthetic scheme
      proposed by Tucker et al. for (S)-Casodex, using (R) or (S)-proline as the chiral
      matrix respectively. 4. ARs were isolated from rat ventral prostate tissue by
      homogenization and differential centrifugation, and used as the receptor source.
      5. AR binding studies were conducted by incubation of the cytosol with 1 nM 3H
      mibolerone (a synthetic androgen) and increasing concentrations of each isomer
      (10(-12) - 10(-5) M). Bound radioligand was quantitated by liquid scintillation
      counting. 6. Ki for (R)-Casodex (11.0 +/- 1.5 nM) was about 30 times lower than
      that of (S)-Casodex (364 +/- 10 nM). Ki for the racemate was 20.2 +/- 2.0 nM. 7.
      This study demonstrated that (R)-Casodex has a higher binding affinity than its
      stereoisomer and suggests that the antiandrogenic activity of racemic Casodex is
      almost completely due to the (R)-isomer.

PMID- 8867997
TI  - Glucuronidation of diflunisal in liver and kidney microsomes of rat and man.
AB  - 1. The glucuronidation of diflunisal to its phenolic (DPG) and acyl glucuronide
      (DAG) was measured in vitro using microsomes prepared from rat (n = 4) and human
      (n = 6) liver and kidney tissue. UGT activities towards bilirubin, 4-nitrophenol
      and (-)-morphine were also determined. 2. beta-Glucuronidase activity towards
      phenolphthalein glucuronide was much lower in microsomes prepared from human
      liver (45.2 +/- 3.1 Fishman Units/mg protein), human kidney (22.0 +/- 3.3 FU/mg),
      and rat kidney (25.1 +/- 2.5 FU/mg) as compared with rat liver (118.7 +/- 8.8
      FU/mg). 3. The formation rate of DAG significantly increased when saccharo-1,4
      lactone, a beta-glucuronidase inhibitor, was added to the rat liver microsomal
      incubation medium. beta-Glucuronidase inhibition, however, had little effect on
      the formation rate of DAG in human liver microsomes, and no effect in rat and
      human kidney microsomes. The formation of DPG was not affected by the microsomal
      beta-glucuronidase activity. 4. Unlike rat kidney microsomes, which only formed
      DAG, human kidney microsomes formed both diflunisal glucuronides. Formation of
      both diflunisal glucuronides in human kidney microsomes (Vmax = 0.97 +/- 0.21 and
      0.27 +/- 0.07 nmol/min/mg for formation of DAG and DPG respectively) represented
      60-70% of the activity found in liver microsomes (Vmax = 1.58 +/- 0.32 and 0.40
      +/- 0.08 nmol/min/mg for formation of DAG and DPG respectively). 5. These results
      demonstrate that the in vitro glucuronidation rate of diflunisal may be affected
      by the microsomal beta-glucuronidase activity particularly when using rat liver
      microsomes. Our results also demonstrate that the human kidney has an important
      UGT-activity towards diflunisal.

PMID- 8867999
TI  - Enzyme kinetics and substrate selectivities of rat glutathione S-transferase
      isoenzymes towards a series of new 2-substituted 1-chloro-4-nitrobenzenes.
AB  - 1. Four different rat glutathione S-transferase (GST) isoenzymes, belonging to
      three different classes, were examined for their GSH conjugating capacity towards
      11 2-substituted 1-chloro-4-nitrobenzene derivatives. Significant differences
      were found in their enzyme kinetic parameters Km, kcat and kcat/Km. 2. Substrates
      with bulky substituents on the ortho-position appeared to have high affinities
      (low Km's) for the active site of the GST-isoenzymes, suggesting that there is
      sufficient space in this area of the active site. A remarkably high Km (low
      affinity) was found for 2-chloro-5-nitropyridine towards all GST-isoenzymes
      examined. 3. GST 3-3 catalysed the reaction between GSH and the substrates most
      efficiently (high kcat) compared with the other GST-isoenzymes. Moreover, GST 3-3
      showed clear substrate selectivities towards the substrates with a
      trifluoromethyl-, chlorine- and bromine-substituent. 1-Chloro-2,4-dinitrobenzene
      and 2-chloro-5-nitrobenzonitrile were most efficiently conjugated by all four GST
      isoenzymes examined. 4. When the rate of the conjugation reactions was followed,
      a linear increase of formation of GS-conjugate could be seen for 2-chloro-5
      nitrobenzonitrile during a much longer period of time than for 1-chloro-2,4
      dinitrobenzene with all GST-isoenzymes examined. Therefore, it is suggested that
      2-chloro-5-nitrobenzonitrile might be recommended as an alternative model
      substrate in GST-research.

PMID- 8867998
TI  - Biotransformation of a somatostatin analogue in precision-cut liver and kidney
      slices from rat, dog and man.
AB  - 1. Cleavage of the glucopyranosyl moiety of the somatostatin analogue SDZ CO 611
      results in the formation of the major metabolite, SDZ CO 610, in liver and kidney
      slices of rat, dog and man, as well as in liver S9 and cytosol of rat and man. 2.
      The rates of SDZ CO 610 formation (nmol/h/mg slice protein) for all three species
      were determined in liver slices for 24 h and the relative order was: rat (0.12) >
      dog (0.096) = man (0.095). The rates of SDZ CO 610 formation (nmol/h/mg slice
      protein) for all three species in kidney were determined, and the relative order
      was: rat (0.29) > dog (0.16) > man (0.10). 3. SDZ CO 610 was rapidly formed by
      rat gut contents in the absence of NADPH, possibly by disaccharide-splitting
      enzymes. 4. Biotransformation of SDZ CO 611 to SDZ CO 610 in human and rat liver
      S9 and cytosol was similar to that found in liver slices cultures indicating that
      cleavage of the glucopyranosyl moiety of SDZ CO 611 could occur in the presence
      and in the absence of cytochrome P450, possibly by glucosidases in liver cytosol.
      5. Rat intestinal homogenate also formed SDZ CO 610 but metabolism was dependent
      upon NADPH, suggestive of a cytochrome P450-dependent reaction.

PMID- 8868000
TI  - Quantitative structure-metabolism relationships for substituted benzoic acids in
      the rabbit: prediction of urinary excretion of glycine and glucuronide
      conjugates.
AB  - 1. Quantitative relationships between molecular physicochemical properties of 24
      substituted benzoic acids and their metabolic fate in the rabbit have been
      investigated using computational chemistry and multivariate statistical methods.
      2. A total of 34 molecular properties were calculated for each compound using
      computational chemistry and were related statistically to the % molar recovery of
      glycine and glucuronide conjugates excreted in the urine of rabbits for the 24
      compounds. 3. Compounds were successfully classified according to their dominant
      metabolic fate based on urinary excretion data, where stepwise linear regression
      analysis of the theoretical property data achieved good predictive fits for
      observed versus predicted % molar urinary recovery as glucuronide conjugates (r2
      = 0.79) and % molar urinary recovery as glycine conjugates (r2 = 0.66). 4.
      Quantitative prediction of the urinary excretion of glucuronide and glycine
      conjugates of the parent compounds was achieved based on a statistical model
      using calculated molecular physicochemical parameters. Interpretation of the
      molecular properties, which are important for predicting the metabolic class,
      should give new insights into basic mechanisms of drug metabolism and underlying
      molecular recognition events that determine disposition and metabolism.

PMID- 8868001
TI  - Metabolism of barnidipine hydrochloride, a potent calcium antagonist, in rat and
      dog.
AB  - 1. In vitro experiments in the rat indicated that barnidipine was metabolized
      extensively in the liver and was catalyzed by P450s. 2. After oral dosing, nine
      metabolites were identified in the urine and bile of rat and dog. No unchanged
      drug was detected in urine and bile. Ester hydrolysis and pyridine formation were
      the main metabolic pathways in urine in both species, whereas glucuronide
      conjugates of the debenzylated metabolite and the hydrolyzed pyrrolidine ester
      were noted in bile. 3. The metabolism of barnidipine in the rat and dog were
      qualitatively similar. Metabolites are generated by one or several of the
      following pathways: (a) N-debenzylation of the side chain, (b) hydrolysis of the
      pyrrolidine ester, (c) oxidation of the dihydropyridine ring to a pyridine ring,
      (d) hydrolysis of the methylester, (e) reduction of the nitro group to the amino
      group, and (f) conjugation of the generated metabolites with glucoronic acid.

PMID- 8868002
TI  - Hplc-nmr identification of the human urinary metabolites of (-)-cis-5-fluoro-1-[2
      (hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine, a nucleoside analogue active
      against human immunodeficiency virus (HIV).
AB  - 1. Human urine samples from a clinical trial of the anti-HIV compound (-)-cis-5
      fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-cyto sin e (BW524W91) have been
      analysed using 19F-nmr and 1H-hplc-nmr spectroscopy. 2. The identities and
      relative levels of the xenobiotic species in the urine have been determined by
      470-MHz 19F-nmr spectroscopy and by directly coupled 600-MHz 1H-hplc-nmr in the
      stop-flow mode with confirmation of the metabolite identities being made by
      comparison with nmr spectra of synthetic standard compounds. 3. The principal
      urinary xenobiotic was the unchanged drug, but the glucuronide ether conjugate at
      the 5' position of BW524W91, one of the two diastereomeric sulphoxides and the
      deaminated metabolite were also characterized. 4. The detection limit of directly
      coupled hplc-600-MHz 1H-nmr spectroscopy was evaluated by measuring two
      dimensional nmr spectra of the glucuronide conjugate of BW524W91 and shown to be
      approximately 1 microgram material for 1H-1H-TOCSY and 20 micrograms metabolite
      for 1H-13C-HMQC spectra for overnight (16 h) acquisition.

PMID- 8868003
TI  - Metabolism of tetramethrin isomers in rat. III. Stereochemistry of reduced
      metabolites.
AB  - 1. Three main urinary metabolites, two isomers of 3-hydroxycyclohexane-1,2
      dicarboximide (3-OH-HPI-1 and 2) and 1,2-tetrahydrodicarboxylic acid (TCDA) were
      purified from rat treated with (1RS, trans)-tetramethrin [3,4,5,6
      tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate]. 2. To elucidate the
      mechanism of formation of these reduced metabolites, the stereochemistry of 3-OH
      HPI-1, 3-OH-HPI-2 and TCDA was clarified by chemical reactions, spectroanalysis
      (nmr) and X-ray analysis. 3. The sole difference in configuration between 3-OH
      HPI-1 and 3-OH-HPI-2 was found to be the orientation of the hydroxyl group to the
      cyclohexane ring, and both of these reduced metabolites showed cis-addition of
      two hydrogens. In contrast, reduction resulted in the trans form with TCDA. 4.
      These findings indicate the existence of two different reduction reaction
      mechanisms in the rat.

PMID- 8868004
TI  - Urinary metabolic profile in rat of 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1
      propanone: a potential radioligand for functional diagnosis of adrenal pathology.
AB  - 1. The metabolism of 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone (2
      MPMP) was studied in the male Sprague-Dawley rat after 50 mg/kg, i.v. dose. 2.
      Organic solvent extracts of urine samples were directly analysed by reversed
      phase gradient hplc. The identified metabolites were also isolated by preparative
      tlc, and analyzed by direct probe mass spectrometry. In the case of conjugated
      metabolites, the urine samples were deconjugated by enzyme hydrolysis prior to
      extraction. The structures of metabolites were confirmed by comparison of their
      chromatographic behaviours, UV spectra, and mass spectra with those of authentic
      standards. 3. The metabolites identified in the 0-24-h urine samples were 2
      hydroxyphenyl-metyrapone (2-OHPMP) and 2-hydroyphenylmetyrapone N-oxide (2-OHPMP
      NO), which were present predominantly as their glucuronide and/or sulphate
      conjugates. 4. 2-MPMP and four of its metabolites present in the 0-24-h urine
      samples were quantified by a reversed-phase hplc method. The mean total urinary
      excretion was 75.4% of the administered dose. The major metabolites present in
      the urine were conjugates of 2-OHPMP-NO (54.4%) and of 2-OHPMP (18.6%). The
      excretion of the unchanged drug, unconjugated 2-OHPMP and 2-OHPMP-NO accounted
      for 1.1, 1.1 and 0.2% of the dose respectively.

PMID- 8868005
TI  - Identification of trimetazidine metabolites in human urine and plasma.
AB  - 1. The objective was to use modern mass spectrometric techniques to update
      current information on the metabolism of trimetazidine in human subjects found by
      previous studies. 2. Urine and plasma samples were taken from four healthy human
      volunteers taking part in a larger kinetic study. Each subject received an oral
      dose of 80-mg trimetazidine daily for 4 days. 3. Identification and quantitation
      of trimetazidine and its metabolites in urine and plasma were achieved using
      modern liquid chromatography-mass spectrometric methods. 4. The major drug
      related component observed in urine and plasma was unchanged trimetazidine. In
      addition to the parent drug, 10 metabolites were detected in urine in
      concentrations ranging from 0.008 (0.01% dose) to 1.094 micrograms.ml-1 (1.4%
      dose). Metabolic profiles following acute and chronic doses of trimetazidine were
      qualitatively similar.

PMID- 8868006
TI  - Plasma and urinary metabolites of efonidipine hydrochloride in man.
AB  - 1. The plasma and urinary metabolite profiles of efonidipine hydrochloride, a new
      dihydropyridine calcium antagonist, have been examined in six healthy male
      volunteers after oral dosing. 2. Unchanged drug in plasma was determined by hplc
      ms. Five metabolites in plasma and five metabolites and unchanged drug in urine
      were identified by hplc. 3. The main plasma metabolites were N-dephenylated
      efonidipine and deaminated-efonidipine. 4. No significant amount of unchanged
      drug was excreted in urine. In the urine collected for 24 h after a oral dosing,
      1.1% of the dose was excreted as deaminated-efonidipine, and 0.5% as a pyridine
      analogue of deaminated-efonidipine.

PMID- 8868007
TI  - Roxatidine versus ranitidine in the treatment of duodenal ulcer: a randomized,
      double blind, controlled, multicenter study in Thailand.
AB  - BACKGROUND: Roxatidine acetate is a novel H2-receptor antagonist and several
      studies have shown that it is effective in healing duodenal ulcers. We evaluated
      the efficacy of roxatidine in a non-western society with particular different
      features and its healing of duodenal ulcers was compared in Thailand with that of
      ranitidine. METHOD: The design was controlled, randomized, double-blind, and
      multicenter. The study recruited a total of 215 patients who were endoscoped at
      the start of the trial and then randomized to receive a single capsule of
      roxatidine acetate, 150 mg, or an identical capsule containing ranitidine, 300
      mg, both to be taken at night. Patients were evaluated at 1, 2, and 4 weeks,
      including endoscopy at the last session, as well as at 6 weeks with repeat
      endoscopy if the ulcer had not healed. RESULT: Both drugs relieved pain rapidly,
      usually within a week, and at repeat endoscopy at 4 weeks most ulcers (78%) were
      healed, 77.0 and 79.5 per cent in ranitidine and roxatidine, and in those
      patients in whom healing was not completed the healing rate had risen appreciably
      to 89.8 and 93.8 per cent respectively at 6 weeks. Small ulcers tended to heal
      quicker than larger ones, but smoking and alcohol intake had no negative effects
      on the results. CONCLUSION: The study was valid proof that roxatidine, in a
      single evening dose of 150 mg, was found to be both safe and effective in the
      rapid healing of duodenal ulcers when compared with 300 mg ranitidine.

PMID- 8868008
TI  - Skull base surgery in Prasat Neurological Institute.
AB  - Skull base technique is very useful for lesions around the base of the skull.
      Additionally, this technique can replace some standard approaches when the
      surgeon wants to avoid excessive retraction and needs better visualization. This
      technique can be used for aneurysms especially a posterior circulation aneurysm
      which is very difficult by standard microsurgical approach. We employed this
      technique and total tumor removal was achieved in some cases. We realize that the
      increasing experience of neurosurgeons, will improve the result. Teamwork as well
      as cooperation between other surgeons is necessary to get the best result from
      this kind of surgery.

PMID- 8868009
TI  - Outcome of pregnancy in IVF-ET cycle at Ramathibodi Hospital.
AB  - As assisted reproductive technology is being developed, in vitro fertilization
      and embryo transfer (IVF-ET) are the treatments of choice for many infertility
      problems. The outcome of pregnancies achieved by IVF-ET is different from that of
      spontaneous pregnancies. In this retrospective study, the outcome of pregnancies
      from 400 IVF treatment cycles performed from October 1991 to October 1994 were
      reported. There were 80 pregnancies (20% per oocyte retrieval, 21.9% per embryo
      transfer) with an increased rate of abortion (30%), multiple pregnancy (20%),
      ectopic pregnancy (6.25%), heterotopic pregnancy (1.25%), preterm delivery
      (11.8%), low birth weight (35.8%) and cesarean section (62.7%). This study shows
      that the complication rate of pregnancies from IVF-ET cycles was higher than that
      found in spontaneous pregnancies. Some complications such as multiple pregnancies
      may be prevented by limiting the number of transferred embryos. From this study,
      all IVF-ET pregnancy should be considered as high risk pregnancies.

PMID- 8868010
TI  - Silicosis and pulmonary tuberculosis in stone-grinding factories in Saraburi,
      Thailand.
AB  - The stone-grinding industry is well known to place its workforce at higher risk
      for silicosis. In addition, workers who are exposed to silica fibers are at a
      higher risk for pulmonary tuberculosis. This study was conducted to determine the
      prevalence levels of silicosis and pulmonary tuberculosis among workers in 33
      factories in 3 subdistricts of Saraburi, Thailand and the associated risk
      factors. Thirty-one of the factories (93.9%) had amounts of either total dust or
      respirable dust exceeding threshold limit values with the average levels of total
      dust and respirable dust of 24.3 +/- 34.6 and 2.4 +/- 1.6 mg/m3 respectively.
      Radiologic patterns indicated that 61 workers (9.0%) had silicosis and 13 workers
      (1.9%) had pulmonary tuberculosis. The prevalence of silicosis and pulmonary
      tuberculosis was significantly associated with years of work. This study
      demonstrated the need for developing and supporting potential primary preventive
      intervention, periodic medical screening as a part of a medical surveillance
      system and a national occupational medical services program.

PMID- 8868011
TI  - Is driving oxygen flow rate clinically important for nebulizer therapy in
      patients with COPD?
AB  - Our study suggests that the administration of bronchodilator drug via nebulizer
      powered by flow rate 6 L/min is more suitable in COPD patients. The oxygen flow
      rates should not be given more than 6 L/min. In this study, we recruited COPD
      patients in a stable stage, in whom the risk of hyperoxic induced hypercarbia is
      less than in the acute exacerbation stage. Thus, in acute exacerbation stage of
      the COPD patients, the rise of carbondioxide should be higher. We recommend that
      the COPD patients should receive bronchodilator drug via the nebulizer,
      especially in acute exacerbation stage, with oxygen flow rate not more than 6
      L/min. The medical personnel must closely observe the clinical signs of the
      patients to prevent the hazard of carbondioxide retention.

PMID- 8868012
TI  - Cell analysis of bronchoalveolar lavage.
AB  - Ninety bronchoalveolar lavage (BAL) of Thai cancerous cases (28), tuberculous
      cases (24); non-tuberculous cases (17) and miscellaneous diseases cases (13) was
      performed for total and differential BAL cell count. This technique could be
      initially used as a guideline for suggestive diagnosis in some suspicious cases
      particularly cancer from tuberculous BAL. The combination in the ratio of
      macrophages to dusty and foamy macrophages below 1.25 and total BAL cell count
      lower than 0.85 x 10(3)/mm3 could suggest a diagnostic indication of cancerous
      BAL rather than tuberculous BAL or other diseases. Tuberculous BAL revealed a
      high percentage of macrophages, low level of dusty and foamy macrophages. Non
      tuberculous BAL could be distinguished from other diseases by the higher
      percentage of neutrophil over 55% and lower percentage in every type of
      macrophages, whereas, a high level in every type of macrophages was found in
      miscellaneous BAL.

PMID- 8868013
TI  - Abnormal pulmonary function among traffic policemen in Bangkok.
AB  - One hundred and seventy four traffic policemen's pulmonary functions were
      measured via vitalograph. Abnormal pulmonary functions occurred in 44 persons
      (25.29%). There was restrictive lung in 30, small airway obstruction in 11 and
      large airway obstruction in 3.

PMID- 8868014
TI  - Adolescent pregnancy with HIV-1 positive in Ramathibodi Hospital 1991-1995.
AB  - In summary, the level of HIV infection among teenagers will increase in our
      community because of their risky behaviour. Education and counselling should be
      the effective strategies to overcome this problem.

PMID- 8868015
TI  - One-stage surgical treatment of pulmonary aspergilloma with cavernostomy and
      muscle transposition flap: a case report.
AB  - A 47-year-old female with cough and recurrent haemoptysis was admitted to
      Ratchaburi Hospital. Chest X-ray revealed a fungal ball in RUL. Aspergillus
      fumigatus was diagnosed by fungus culture from the material of the fungus ball. A
      one-stage cavernostomy was done and the fungus ball was then removed,
      obliteration of the cavity with intrathoracic transposition of extrathoracic
      skeletal muscle (latissimus dorsi) was performed. She recovered well, and
      haemoptysis disappeared. The body weight increased to 48 kgs in 4 postoperative
      months. (Fig. 6)

PMID- 8868016
TI  - Efficacy of acarbose as monotherapy in NIDDM patients.
AB  - The efficacy and safety of acarbose (100 mg three times a day for 12 weeks) was
      investigated in an open study in patients with non-insulin dependent diabetes
      mellitus who could not achieve satisfactory glycaemic control by diet alone.
      Acarbose significantly decreased fasting plasma glucose from 165.9 +/- 16.0 mg/dl
      to 159.5 +/- 16.9 mg/dl (P value < 0.01). The reduction of postprandial plasma
      glucose was 11.2 per cent and 9.8 per cent for 1 hour and 2 hours respectively.
      HbAic also significantly decreased from the baseline. The most common side
      effects were mild to moderate flatulence and abdominal distension. There were no
      significant changes in body weight, lipid profile and other biochemical
      parameters. These results indicate that treatment with acarbose is safe and
      effective in adjunct to dietary therapy for the treatment of NIDDM.

PMID- 8868017
TI  - A comparison of serum magnesium sulfate levels in pregnant women with severe
      preeclampsia between intravenous and intramuscular magnesium sulfate regimens: a
      randomized controlled trial.
AB  - The frequency of blood samples that achieved therapeutic level was lower in the
      group of maintenance with intravenous regimen than the intramuscular regimen
      significantly at 15, 30, 60, 120 and 240 minutes after loading dose. The mean
      level of serum magnesium sulfate in the intravenous group was significantly lower
      than intramuscular group. This study supported to choose the maintenance by
      intramuscular regimen. However, further study is required to analyse the effect
      of higher level of magnesium sulfate in Thai patients.

PMID- 8868018
TI  - Corticosteroid in tuberculous meningitis.
AB  - We assessed the benefit of prednisolone regimen in adult-patients with
      tuberculous meningitis by a randomised, double-blind trial. 59 patients were
      treated with combined antituberculous drugs and randomised to receive oral
      prednisolone regimen or a placebo. There were 29 and 30 patients in the treatment
      and placebo groups respectively. The results revealed that prednisolone was not
      beneficial in patients with severe brain lesions, increased intracranial pressure
      and cranial nerve palsies. The role of prednisolone in patients with paraparesis,
      visual impairment and newly developed neurological complications during treatment
      needs further study.

PMID- 8868019
TI  - Effects of occupational lead exposure on spermatogenesis.
AB  - In summary, there were significant differences in blood and semen lead levels, LH
      levels and prolactin levels in workmen who were exposed to lead. However, all
      hormonal profiles still remained within the normal adult range for Thai men.
      Higher levels of blood lead were found to have no significant effect on the sperm
      variables and hormonal profiles except testosterone levels at second follow-up
      and prolactin levels at sixth follow-up. However, these differences were not
      consistent during the study period. It should be noted that the present data are
      preliminary, pertain only to short-term exposure and require confirmation. The
      actual prospective long-term risk of lead exposure, remains to be determined.
      However, our study highlights the feasibility and importance of a prospective
      cohort study in assessment of the risk of lead exposure on male reproductive
      system. Long-term longitudinal controlled studies of semen quality and hormonal
      profiles in workmen examined before and during lead exposure and prospective
      studies of time to pregnancy in couples attempting to achieve pregnancy are
      probably necessary in order to obtain further knowledge. This study also
      indicates that the reproductive function surveillance of these workmen must be
      investigated as well as other physical health. In conclusion, an increase of
      blood lead levels due to occupational exposure cause no immediate and significant
      changes in spermatogenesis and hormonal profiles.

PMID- 8868020
TI  - Relationship between exercise capacity and left ventricular function in aortic
      and mitral regurgitation.
AB  - The exercise capacity as assessed by treadmill exercise or functional class from
      clinical history cannot predict standard echocardiographic findings in patients
      with AR/MR, in terms of EF, LVDs, ESVI. Therefore, exercise capacity cannot be
      used to predict the timing for surgery in those patients. However, symptomatic
      patients with dilated LV usually have low LVEF such as in our group.

PMID- 8868021
TI  - Left ventricular hypertrophy: relationship of echocardiographic and
      electrocardiographic findings in idiopathic dilated cardiomyopathy.
AB  - Diagnosis of left ventricular hypertrophy is important in patients with cardiac
      disease. To test the correlation of echocardiographic and electrocardiographic
      findings for diagnosis of left ventricular hypertrophy in Idiopathic Dilated
      Cardiomyopathy (IDC), 18 patients with proven IDC were examined. There were 15
      males and 3 females, ages ranged from 22-60 years (mean 43 +/- 10.7). LV mass
      index ranged from 134.4-421.2 g/m2 (mean 187.8 +/- 68.6). All 18 patients had LVH
      by echocardiography but only 10 patients (55.6%) had LVH by using ECG Romhilt
      Estes scoring system. The correlation between echocardiographic and
      electrocardiographic findings for diagnosis LVH was not significant (r = 0.026; p
      = 0.935) and echocardiography was better than electrocardiography for diagnosis
      of LVH in IDC.

PMID- 8868022
TI  - Peripheral and spinal SEPs in the extraoperative evaluation of non-penetrating
      brachial plexus injuries.
AB  - Peripheral (N9) and cervical (N13) SEPs as recorded at Erb's point and over the
      fifth cervical spinous process respectively, from the musculocutaneous, median
      and ulnar nerve stimulation, were examined in 30 cases of unilateral non
      penetrating brachial plexus injuries. Among 14 cases (42 nerves examined) who
      underwent surgical exploration, the SEPs were found to give good prediction of
      the actual lesions in 9 cases, gave helpful information in 1 and correlated
      partially in the other 4. In none of the cases did SEPs give totally misleading
      data. The results indicated that this SEPs testing package was simple, convenient
      and could be a useful adjunct to the conventional electrodiagnosis in the
      evaluation of non-penetrating brachial plexus injuries.

PMID- 8868023
TI  - Recent approach for common bile duct stone.
AB  - One hundred and thirty-nine patients underwent cholecystectomy from 1992 through
      1994. Twenty-seven patients demonstrated preoperative risk factors for common
      bile duct (CBD) stones and underwent endoscopic retrograde
      cholangiopancreatography (ERCP). ERCPs were successful in 25 (92.6%) patients and
      there were two failures, due to pyloric obstruction and duodenal diverticulum. Of
      25 patients suspected of harboring CBD stones, 48 per cent had bile duct stones
      on preoperative ERCP. In contrast, 3 of 112 patients (2.7%) thought not to have
      stones indeed had choledocholithiasis. Laparoscopic cholecystectomies (LC) were
      performed on 19 (76%) of 25 patients. Of these 19, 13 (68%) had negative ERCP, 5
      (26.3%) had stones removed by endoscopic sphincterotomy (ES), and only one was
      accomplished with laparoscopic choledochoduodenostomy. Open exploration of CBD
      was performed on 3 patients who had complex CBD stones and bilio-enteric bypasses
      in 2 patients who had multiple impacted stones in the left main duct. Overall,
      three endoscopic failures (2 ERCPs and 1 ES) were managed by open biliary
      surgery. We suggest that patients with complex CBD stones who are not successful
      in stone extraction via ES should undergo open CBD surgery. LC following
      successful ES has been accepted as the gold standard for the treatment of simple
      CBD stones.

PMID- 8868024
TI  - Incorrect use of metered dose inhaler by pediatric residents.
AB  - Currently press-and-breath metered dose inhalers (MDIs) are widely prescribed but
      are often difficult for many patients to properly use. However many medical
      personnel cannot use the MDIs correctly. We administered a question and observed
      usage of a placebo metered dose inhaler with ad-on spacer (Nebuhaler) among 127
      second year pediatric residents. Forty-eight per cent of the residents performed
      at least six of nine steps correctly. The two most common errors made by
      participants were not to place mouthpiece tightly between teeth and lips (64%)
      and failure to breath out to functional residual capacity before actuation
      (55.3%). Of the residents with improper timing of actuation (49%) all actuated
      the canister before starting inhalation. (5 seconds or longer time). We conclude
      that (1) pediatricians should have additional instruction in proper MDIs usage
      and practice with the asthmatic child and (2) routine assessment of MDIs
      technique should be instituted as standard practice care.

PMID- 8868025
TI  - Retailers' compliance to the law banning cigarette sale to minors.
AB  - In order to prevent smoking addiction, a law banning cigarette sales to minors
      was enacted in 1992. In market economy countries, studies have shown that
      enforcement of such a law is not effective(1,2). Almost three years after
      enactment of the law in this country, there is no evidence regarding the extent
      of law enforcement. If law enforcement is going to be effective, concerns of
      politicians and authorities must be mobilized. This study aims at testing
      retailer compliance to the law. Students aged 9-17 years were sent into 773
      stores to buy a pack of cigarettes. The stores were located on main streets in 5
      major cities. It was found that nearly all (90.6%) of the retailers violated the
      law. Ten per cent of the stores showed a sticker stating that "cigarette sale to
      children under 18 years is banned". However, all of them did sell cigarettes to
      the students. A set of intervention will be tested to find out effective
      approaches for law enforcement.

PMID- 8868026
TI  - Treatment of tonsillar crypt infection with CO2 laser: a preliminary report.
AB  - The treatment of tonsillar crypt infection by CO2 laser vaporization of the crypt
      and tonsillar tissue is safe, effective and cost effective. The procedure
      requires short operative time without any risk from general anesthesia and can be
      performed on out-patient basis. We advise the procedure as an alternative option
      to treat tonsillar crypt infection instead of standard tonsillectomy, but further
      studies should be carried out.

PMID- 8868027
TI  - Effects of hypertrichotic agents on follicular and nonfollicular cells in vitro.
AB  - Our previous studies revealed that topical minoxidil induced an increased rate of
      DNA synthesis in both dermal papilla and follicular germinal cells in early
      anagen and bulbar matrix as well as outer root sheath and perifollicular
      fibrocytic cells in mid and late anagen follicles in the bald scalp of the stump
      tailed macaque. However, the epidermis and dermal fibrocytes showed no response.
      To determine the specific action of hypertrichotic agents on follicular cells, we
      examined the effects of two potent hypertrichotic agents, minoxidil and
      cyclosporin, on the DNA synthesis of cultured cells derived from either
      follicular cells (dermal papillar, perifollicular fibrocytic and outer root
      sheath cells) obtained from human and macaque scalps or nonfollicular cells
      (fibrocytes and epidermal keratinocytes) from human and macaque foreskin, palm
      and sole regions and the 3T3 cell line. Cultured subconfluent cells from the
      above follicular and nonfollicular specimens were incubated with either minoxidil
      (0.01-2 mM) or cyclosporin (0.01-100 mM) in medium (serum-free DMEM) for 48 h,
      then 3H-thymidine was added for the final 6 h. Minoxidil induced a significant
      increase in DNA synthesis in all follicular cells in a dose-specific manner
      (maximum rate at 0.5 mM for dermal papilla and perifollicular fibrocytic cells
      and 0.1 mM for outer root sheath cells). The perifollicular fibrocytic cells
      appeared to have a potentiality similar to that of the dermal papilla cells.
      Nonfollicular cells showed no response to minoxidil; 3T3 cells were rather
      suppressed. Cyclosporin appeared to have rather suppressive effects on both
      follicular and nonfollicular cells. These results suggest that minoxidil has a
      specific affinity to hair follicular cells and induced their cell proliferation.
      Although cyclosporin is known as a potent hypertrichotic agent, our studies on
      cultured follicular cells showed no direct proliferative effect. The
      hypertrichotic mechanism of cyclosporin appeared to be different from that of
      minoxidil.

PMID- 8868028
TI  - Vaginal keratinization during the estrous cycle in rats: a model for evaluating
      retinoid activity.
AB  - A model is described for evaluating the activity of a retinoid based on its
      effect on the keratinization of the vaginal epithelium that occurs on estrus (day
      4) of a 4-day cycle in female rats. This keratinization process is dependent on
      the endogenous estradiol (E2) secreted between the evening of diestrus 2 (day 2)
      and that of proestrus (day 3). Various doses of all-transretinoic acid (tRA) were
      injected at different time points during the estrous cycle and the vaginal
      keratinization was assessed by microscope examination of unstained native or
      Papanicolaou-stained smear preparations. Additionally, the preovulatory E2
      secretion was measured and ovaries were histologically examined. A single
      injection of 10 mg/kg tRA either on diestrus 2 (evening) or on proestrus (early
      morning) was able to induce a complete inhibition of the vaginal keratinization
      in more than 80% of the cases. This can be considered as a direct effect on the
      vaginal epithelial differentiation since neither the E2 secretion nor the
      ovulatory process were affected. The inhibition of vaginal keratinization can be
      used as a rapid and convenient in vivo model for screening retinoid candidates
      with antikeratinizing activity.

PMID- 8868029
TI  - Percutaneous absorption, excretion and metabolism of all-trans-retinoyl beta
      glucuronide and of all-trans-retinoic acid in the rat.
AB  - The purpose of these studies was to compare directly the percutaneous
      absorption,excretion and metabolism of all-trans-retinoyl beta-glucuronide (RAG),
      a nontoxic retinoid, with all-trans-retinoic acid (RA) in the rat. Previously, it
      was demonstrated that topical treatment of human acne with either RAG or RA in
      cream resulted in a significant reduction of lesions. Whereas 0.1% RA showed
      adverse effects, concentrations of RAG up to 2.4% did not cause any adverse
      reactions. In the present studies, radiolabeled RAG or RA, dispersed in a water
      based cream, was applied to the shaved dorsal skin of vitamin A-sufficient rats.
      Both RAG and RA were absorbed from the skin in a similar way. In both cases,
      radioactivity peaked in the plasma within 2-4 h and within the liver at 4-12 h.
      During a 7-day period, the overall excretion of radioactivity derived from RA and
      RAG in the feces and urine were similar, e.g. 17 and 12%, respectively. it is
      concluded that: (1) the transport, metabolism and excretion of topically applied
      radioactive RA and RAG are similar, although not identical, in the rat and (2)
      the toxic skin manifestations induced by RA but not by RAG cannot be attributed
      to major differences in their overall absorption, metabolism and excretion.

PMID- 8868030
TI  - Retinoids can be classified according to their effects on vitamin A metabolism in
      HeLa cells.
AB  - Although retinoids may exert their action via binding to nuclear retinoic acid
      receptors (RARs), other mechanisms of action are not excluded. For example, the
      anti-acne drug, isotretinoin, lacks affinity for the receptors, but is a very
      potent inhibitor of endogenous vitamin A metabolism in human epidermal cells. To
      further extend this observation, we studied the effect of 12 different retinoids
      on the metabolism of [3H]retinol ([3H]ROH) in HeLa cells, previously shown to
      produce constant levels of 3,4-didehydroretinol (ddROH). The cells were cultured
      in the presence of the unlabeled retiniods for 20 h, followed by 4 h incubation
      with [3H]ROH. The accumulation of [3H]ROH and [3H]ddROH in cellular extracts was
      analysed by HPLC. Addition of 10(-10) to 10(-5) M of four naturally occurring
      isomers of retinoic acid caused a 4- to 6-fold increase in [3H]ROH accumulation
      and an 80% decrease in [3H]ddROH. Addition of synthetic retinoids with a terminal
      carboxyl (CD270, CD271, CD367 and Ro 13-7410) decreased the [3H]ddROH
      accumulation with about 70%, but hardly at all affected the accumulation of
      [3H]ROH. We conclude that cultured HeLa cells appear to be useful for screening
      retinoids for their effects on vitamin A metabolism showing that a terminal
      carboxylic acid is a prerequisite for any major effects on metabolism to occur.
      Whether this effect is due to interaction with RARs or to competitive inhibition
      of vitamin-A-metabolizing enzymes demands to be studied.

PMID- 8868031
TI  - Synthetic wound dressings--evaluation of interactions with epithelial and dermal
      cells in vitro.
AB  - Comparative testing of seven wound dressings (WD) has been performed with human
      HaCaT keratinocyte and mouse 3T3 fibroblast cultures. To assess biocompatibility,
      morphologic examinations were combined with cell counting. Supernatants were
      subjected to measurements of tissue peptide antigen (TPS), soluble intercellular
      adhesion molecule 1 (ICAM-1), and interleukins (IL-1 alpha, -1 beta, -6).
      Furthermore, monoxygenation, the reduced glutathione/oxidized gluthathione
      (GSH/GSSG) ratio and lipid peroxides were determined. Initial morphologic events
      were noted within the first day of exposure to WD. After 72 h, inhibition of cell
      growth was observed in the presence of hydrocolloids and hydrogels. The
      cytochrome-P-450-dependent ethoxyresorufin 0-deethylation rate and the GSH/GSSG
      ratio were not altered by WD in HaCaT cells. Lipid peroxide generation, IL-1 and
      ICAM-1 were scarcely detectable. TPS and IL-6 release indicate the presence of an
      'activated stage' of keratinocytes and fibroblasts exposed to WD. Peptide release
      in vivo may contribute to the beneficial effects of modern dressings in the
      treatment of superficial cutaneous wounds.

PMID- 8868032
TI  - Simultaneous absorption of copper and zinc through human skin in vitro: influence
      of counter-ion and vehicle.
AB  - Copper and zinc percutaneous absorptions were assessed in vitro using sliced
      human skin and both petrolatum and hydrophilic gels as vehicles. Applied
      quantities were largely in excess for the duration of the experiment (72 h). The
      absorption of sulphates and chlorides was compared. The cumulated amount
      recovered in receptor fluid was below 50 micrograms/cm2. The apparent
      permeability constant values kept in the range of 10(-6) cm h-1, except for ZnCl2
      in gel vehicle (2.9 10(-5) cm h-1). With the exception of CuCl2 in gel vehicle,
      chlorides gave higher absorption rates than sulphates. This can be related to the
      higher octanol-water partition coefficient of chlorides. Storage within the
      epidermis was found to be equal to or greater than, and within the dermis equal
      to or lower than the 72 hour cumulative amount in receptor fluid. No difference
      was found in this respect between copper an d zinc. This work confirms the poor
      absorption of electrolytes through normal human skin, whatever the vehicle used.

PMID- 8868033
TI  - Diethylene glycol monoethyl ether (Transcutol) displays antiproliferative
      properties alone and in combination with xanthines.
AB  - In the present study we have investigated the effects of diethylene glycol
      monoethyl ether (Transcutol) in combination with theophylline, caffeine and
      dyphylline and alone on 3T3 mouse fibroblast proliferation. These three xanthines
      (1-0.01 mM) inhibited fibroblast proliferation by themselves. Enhancement of the
      effect was detected by addition of 1 and 0.1 mM Transcutol. Transcutol alone also
      displayed a dose-dependent inhibition (2-0.01 mM) of both 3T3 and human normal
      and psoriatic fibroblasts, although normal human fibroblasts were the least
      sensitive to Transcutol antiproliferative activity. Transcutol was assessed for
      its antiproliferative effects on YAC lymphoma and P-815 mastocytoma human cell
      lines. Transcutol inhibited cell proliferation of both these cell lines, being
      more effective towards P-815 mastocytoma (at 2 mM it displayed 3.95-fold vs. 2.4
      fold inhibition towards YAC lymphoma). In conclusion, we have shown that
      Transcutol has antiproliferative effects on 3T3 murine, human normal and
      psoriatic fibroblasts and tumour cell lines. In addition it enhances xanthine
      antiproliferative effects on 3T3 fibroblasts. Therefore it might be a useful
      topical drug alone or in combination with xanthines in the treatment of skin
      hyperproliferative disorders.

PMID- 8868034
TI  - A new method for in vivo evaluation of antimicrobial agents by translocation of
      complex dense populations of cutaneous bacteria.
AB  - Previously, we described methods for measuring in vivo antimicrobial activity in
      which the resident bacterial flora of the forearm is expanded by occlusion with
      an impermeable plastic film, test agents are applied and quantitative cultures
      are obtained at varying time points. This methodology allows for an in vivo
      quantitative assessment of antimicrobial effects directed against a dense flora
      comprised primarily of staphylococci. This method may not be applicable to
      situations in which there is a high density of multiple species of bacteria. We
      describe herein new methods which permit in vivo determination of antimicrobial
      activity against a dense, mixed flora. Swabs moistened with a dilute nonionic
      detergent are used to remove bacteria from the subject's axilla or groin which
      are then translocated to the subject's forearm. Occlusion of the forearm with a
      large, sterile plastic chamber provides the necessary humid environment to yield
      a dense flora (10(5)-10(6) CFU) consisting of gram-positive cocci, gram-positive
      coryneforms and gram-negative rods. In this manner, multiple test sites are
      created on each forearm allowing for the simultaneous evaluation of multiple
      antimicrobial agents in a single subject. This method allows for the evaluation
      of the immediate, as well as sustained, in vivo bactericidal effect of an
      antimicrobial agent against a dense mixed flora with quantitative cultures
      obtained at varying time points after application of the test agent. Furthermore,
      ecological pressures which select for resistant organisms or allow for an
      overgrowth of nonsensitive bacteria can be evaluated by determining the
      composition of the flora after single or repeated applications of a test agent.
      The testing methodologies described herein can provide relevant information
      regarding the antimicrobial effectiveness of an agent in a variety of situations
      such as use against the axillary flora (including its utility as a deodorant),
      use as a perineal cleanser for critically ill, hospitalized patients and use in
      situations where a dense mixed flora exists, e.g. stasis ulcers and infected
      intertriginous dermatoses.

PMID- 8868035
TI  - A critical comparison of methods to quantify stratum corneum removed by tape
      stripping.
AB  - Skin surface stripping with adhesive tape has been used to study the barrier
      function of the stratum corneum. Usually, the amount of stratum corneum removed
      by stripping is not linearly proportional to the number of strips removed. The
      generally accepted quantitative method to determine the amount of stratum corneum
      material on a tape strip is weighing. This method however has certain drawbacks,
      it is time consuming and laborious because tape strips have to be weighed twice
      and sometimes it cannot be used to determine concentration profiles in the skin
      of active substances in topically applied vehicles. In this paper, the accuracy
      and reliability of an alternative method to determine the amount of stratum
      corneum removed by tape stripping of the skin was investigated and compared to
      weighing. It is based on the spectrophotometric examination of the tape. The
      light absorption by the proteins on the tape is correlated to the weight of the
      stratum corneum material. This method was found to be easier and faster than
      weighing, but it was less reliable because the light scattering of the stratum
      corneum on the tape largely overshadowed the absorption of the proteins. The
      light scattering showed a linear increase with an increasing amount of material
      on the tape, but with a large variability, resulting in calibration curves with
      correlations of 0.8400. However, direct spectroscopic analysis of stratum corneum
      tape strips has some distinct advantages even if it cannot be used for the exact
      quantification of stratum corneum proteins. With direct spectroscopic
      measurements, a tape strip can be laterally examined to inspect its homogeneity.
      Direct spectroscopic measurements on tape strips might also be employed to
      investigate the lateral and in-depth distribution of strongly light-absorbing
      substances in the stratum corneum.

PMID- 8868036
TI  - Alcohol and hypertension--kill or cure?
AB  - An association between alcohol consumption and blood pressure levels has been
      observed in over 60 population studies world wide. The relationship is generally
      linear but with some studies showing a threshold effect at around 2-3 standard
      drinks a day. Effects are seen with all types of alcoholic beverages, and in men
      and women. The affect appears additive to effects of obesity and higher dose oral
      contraceptives. Studies of acute effects of alcohol suggest an initial
      vasodilator response, while population studies suggest that heavy drinkers may
      show some rebound hypertension. Randomized controlled trials show that reducing
      alcohol consumption lowers blood pressure in both treated and untreated
      hypertensives. Mechanisms of alcohol induced hypertension are still unclear.
      Despite predisposing to hypertension, regular light to moderate drinking (1-4
      standard drinks a day) appears to protect against coronary deaths and ischaemic
      strokes, while heavier drinking increases the risk of haemorrhagic stroke and
      heart disease. There is some suggestion that wine drinking may be associated with
      lower cardiovascular risks, however in a study of 343 working men we found that
      beverage preference and drinking patterns correlated strongly with diet habits,
      smoking education and socioeconomic status, factors that are likely to confound
      the interpretation of epidemiological studies suggesting favourable
      cardiovascular effects to a particular beverage. Although light drinkers have
      lower mortality than non drinkers those drinking more than 2 standard alcohol
      drinks per day show a rising mortality as well as an increased risk of
      hypertension. Those facts should be the basis of public health advice on 'safe'
      levels of drinking.

PMID- 8868037
TI  - Significance of physical activity for prevention and control of hypertension.
AB  - The beneficial effect of habitual physical exercise, and physical fitness, on
      blood pressure has been reported in the past. However, the reported fall in blood
      pressure, associated with physical exercise, could be related to at least one
      confounding factor. That is, the independent effect of weight loss caused by
      physical exercise, on blood pressure. Exercise results in loss of body fat, a
      redistribution of fat stores, and weight loss. All of these are associated with a
      concomitant reduction in blood pressure. It is not clear whether the reduction in
      blood pressure is caused independently by a decrease in caloric intake alone, or
      an increase in physical activity, or the combination of the two. This is
      particularly true in the case of primary prevention of hypertension in the
      community where an effective and acceptable strategy for life-style modification
      has to be developed; a strategy which must be based on valid scientific evidence.
      The Trial of Hypertension Prevention (TOHP), a large scale randomized clinical
      trial, was designed to test the hypothesis on the efficacy of weight loss
      (induced by a combination of reductions in caloric intake and increased physical
      exercise) on primary prevention of hypertension. Eligible participants were
      randomized into either the weight loss group, or the control group. The exercise
      component of the weight loss program included mild exercise, 3-4 days a week for
      35-40 minutes at an intensity of 40-45% of heart rate reserve. The dietary
      component included a reduction in caloric intake to less than 1200 KCal per day.
      After 18 months, the difference in weight loss between the two groups was 3.9 Kg
      in favor of the dietary modification and exercise (P < 0.01). This was
      accompanied with a significant reduction in blood pressure (P < 0.01). Weight
      loss was a significant predictor for blood pressure change over time (P < 0.001).
      These findings confirm the efficacy of maintaining an ideal body weight, by a
      program which combines physical exercise and reduction in caloric intake, on
      primary prevention of hypertension in the community.

PMID- 8868038
TI  - Tobacco addiction and hypertension.
AB  - The significance of smoking in the hypertensive patient may be unappreciated. The
      risk of hypertension may be tripled in such patients. Tobacco addiction may also
      compromise the treatment of hypertensives. The importance of smoking cessation
      for hypertensive smokers cannot be overemphasized and should be seen as
      fundamental. Nicotine replacement therapy (NRT), when used appropriately, can
      enhance the likelihood of cessation. All smokers, but particularly hypertensive
      smokers, should be advised to quit and offered specific and ongoing assistance in
      this respect.

PMID- 8868039
TI  - Pharmacoeconomics of hypertension control: basic principles of economic
      evaluation.
AB  - Pharmacoeconomics, the science of assigning costs and outcomes of drug therapy
      can be applied to antihypertensive drug therapy. There are five principle tools:
      cost identification, cost minimization, cost benefit, cost effectiveness and cost
      utility. If only drug aquisition costs are considered, there are marked
      differences among antihypertensive drug classes. These differences become less
      marked when the costs per quality adjusted life year are calculated. Often,
      differences among patients rather than differences among drug prices account for
      the bulk of variation.

PMID- 8868040
TI  - The cost-effectiveness of hypertension treatment in Sweden: an analysis of the
      criteria for intervention and the choice of drug treatment.
AB  - Results of an analysis of the cost-effectiveness of hypertension treatment in
      Sweden are presented. The cost per life-year gained decreases with age for both
      men and women and is relatively low for middle-aged and older men and women even
      in the blood pressure range 90-94 mmHg. The results indicate that it is in
      general cost-effective to treat middle-aged and older men and women in Sweden
      with a diastolic blood pressure > or = 90 mmHg, but that it is questionable
      whether it is in general cost-effective to treat younger men and women with mild
      hypertension. It is furthermore shown that ACE-inhibitors and calcium-antagonists
      may be cost-effective in some patient groups at a high risk of coronary heart
      disease, if they achieve the epidemiologically expected risk reduction for
      coronary heart disease. Since an improved risk reduction has not been
      demonstrated in clinical trials ACE-inhibitors and calcium-antagonists cannot,
      however, at present be recommended for hypertension treatment in any patient
      groups unless treatment with diuretics and beta-blockers is contraindicated.

PMID- 8868041
TI  - Ambulatory blood pressure monitoring in treated hypertensive patients-
      implications for clinical practice.
AB  - Studies involving patients receiving longterm antihypertensive therapy have
      demonstrated a high prevalence of a white coat effect both in the tertiary care
      setting and in the community. The likelihood of finding a white coat effect is
      greater in patients with higher office systolic blood pressures and in women. The
      possibility that some hypertensive patients in the community may be receiving
      unnecessary therapy is currently being investigated in a study involving 98
      uncomplicated hypertensive patients who have had treatment withdrawn for up to
      three years. To date, it appears that at least 40% of such patients may remain
      off treatment without re-developing hypertension or exhibiting any increase in
      left ventricular mass. Physicians should follow existing recommendations on the
      use of ambulatory blood pressure recording in order to avoid over-diagnosis and
      unnecessary treatment of hypertension.

PMID- 8868042
TI  - Hypertension can be treated effectively without increasing the cost of care.
AB  - There is little reason to believe that patients with hypertension cannot be
      treated effectively without increasing the cost of care. Yet costs in the United
      States continue to increase. It is of interest to review some of the reasons for
      this and to emphasize that the management of hypertension has been successfully
      carried out over the past 20-30 years without the use of expensive technology or
      complicated treatment programs. This is an important message to non
      industrialized nations that are starting hypertension treatment programs.
      Hypertension costs can be controlled by: (1) limiting the complexities of the
      initial evaluation, avoiding the temptation to employ technologies which have not
      been shown to improve outcome, and (2) by selecting therapy based on data that
      have been collected over the past 20 years, and not on the latest promotional
      efforts. In addition, there is evidence that limiting physician visits to 2, 3 or
      at the most 4 per year is adequate to control the majority of hypertensive
      patients after initial blood pressure control is obtained--another important
      factor in the cost of care ($). There is no evidence that a more expensive
      approach to management will improve outcome compared to a less costly approach.

PMID- 8868043
TI  - Voltage drives a long segment of polar residues of colicins across membranes.

PMID- 8868044
TI  - A new technique for probing inter-membrane interactions.

PMID- 8868045
TI  - Major transmembrane movement associated with colicin Ia channel gating.
AB  - Colicin Ia, a bacterial protein toxin of 626 amino acid residues, forms voltage
      dependent channels in planar lipid bilayer membranes. We have exploited the high
      affinity binding of streptavidin to biotin to map the topology of the channel
      forming domain (roughly 175 residues of the COOH-terminal end) with respect to
      the membrane. That is, we have determined, for the channel's open and closed
      states, which parts of this domain are exposed to the aqueous solutions on either
      side of the membrane and which are inserted into the bilayer. This was done by
      biotinylating cysteine residues introduced by site-directed mutagenesis, and
      monitoring by electrophysiological methods the effect of streptavidin addition on
      channel behavior. We have identified a region of at least 68 residues that flips
      back and forth across the membrane in association with channel opening and
      closing. This identification was based on our observations that for mutants
      biotinylated in this region, streptavidin added to the cis (colicin-containing)
      compartment interfered with channel opening, and trans streptavidin interfered
      with channel closing. (If biotin was linked to the colicin by a disulfide bond,
      the effects of streptavidin on channel closing could be reversed by detaching the
      streptavidin-biotin complex from the colicin, using a water-soluble reducing
      agent. This showed that the cysteine sulfur, not just the biotin, is exposed to
      the trans solution). The upstream and downstream segments flanking the
      translocated region move into and out of the bilayer during channel opening and
      closing, forming two transmembrane segments. Surprisingly, if any of several
      residues near the upstream end of the translocated region is held on the cis side
      by streptavidin, the colicin still forms voltage-dependent channels, indicating
      that a part of the protein that normally is fully translocated across the
      membrane can become the upstream transmembrane segment. Evidently, the identity
      of the upstream transmembrane segment is not crucial to channel formation, and
      several open channel structures can exist.

PMID- 8868046
TI  - Resonance energy transfer imaging of phospholipid vesicle interaction with a
      planar phospholipid membrane: undulations and attachment sites in the region of
      calcium-mediated membrane--membrane adhesion.
AB  - Membrane fusion of a phospholipid vesicle with a planar lipid bilayer is preceded
      by an initial prefusion stage in which a region of the vesicle membrane adheres
      to the planar membrane. A resonance energy transfer (RET) imaging microscope,
      with measured spectral transfer functions and a pair of radiometrically
      calibrated video cameras, was used to determine both the area of the contact
      region and the distances between the membranes within this zone. Large vesicles
      (5-20 microns diam) were labeled with the donor fluorophore coumarin
      phosphatidylethanolamine (PE), while the planar membrane was labeled with the
      acceptor rhodamine-PE. The donor was excited with 390 nm light, and separate
      images of donor and acceptor emission were formed by the microscope. Distances
      between the membranes at each location in the image were determined from the RET
      rate constant (kt) computed from the acceptor:donor emission intensity ratio. In
      the absence of an osmotic gradient, the vesicles stably adhered to the planar
      membrane, and the dyes did not migrate between membranes. The region of contact
      was detected as an area of planar membrane, coincident with the vesicle image,
      over which rhodamine fluorescence was sensitized by RET. The total area of the
      contact region depended biphasically on the Ca2+ concentration, but the distance
      between the bilayers in this zone decreased with increasing [Ca2+]. The changes
      in area and separation were probably related to divalent cation effects on
      electrostatic screening and binding to charged membranes. At each [Ca2+], the
      intermembrane separation varied between 1 and 6 nm within each contact region,
      indicating membrane undulation prior to adhesion. Intermembrane separation
      distances < or = 2 nm were localized to discrete sites that formed in an ordered
      arrangement throughout the contact region. The area of the contact region
      occupied by these punctate attachment sites was increased at high [Ca2+].
      Membrane fusion may be initiated at these sites of closest membrane apposition.

PMID- 8868047
TI  - Micromolar 4-aminopyridine enhances invasion of a vertebrate neurosecretory
      terminal arborization: optical recording of action potential propagation using an
      ultrafast photodiode-MOSFET camera and a photodiode array.
AB  - Modulation of the amount of neuropeptide released from a neurosecretory tissue
      may be achieved by different means. These include alterations in the quantity
      secreted from each active nerve terminal or in the actual number of terminals
      activated. From the vertebrate hypothalamus, magnocellular neurons project their
      axons as bundles of fibers through the median eminence and infundibular stalk to
      arborize extensively and terminate in the neurohypophysis, where the
      neurohypophysial peptides and proteins are released into the circulation by a Ca
      dependent mechanism. Elevating [Ca2+]o increases the magnitude of an intrinsic
      optical change in the neurohypophysial terminals that is intimately related to
      the quantity of neuropeptide released. Similarly, the addition of micromolar
      concentrations of 4-aminopyridine to the bathing solution enhances this change in
      large angle light scattering. However, we show here that, while these effects are
      superficially similar, they reflect different mechanisms of action. Evidence from
      intrinsic optical signals (light scattering) and extrinsic (potentiometric dye)
      absorption changes suggests that calcium increases the amount of neuropeptide
      released from each active terminal in the classical manner, while 4-aminopyridine
      exerts its secretagogue action by enhancing the invasion of action potentials
      into the magno-cellular neuron's terminal arborization, increasing the actual
      number of terminals activated. Physiologically, electrical invasion of the
      complex terminal arborization in the neurohypophysis may represent an extremely
      sensitive control point for modulation of peptide secretion. This would be
      especially effective in a neurohaemal organ like the posterior pituitary, where,
      in contrast with a collection of presynaptic terminals, the precise location of
      release is less important than the quantity released.

PMID- 8868048
TI  - Voltage-jump relaxation kinetics for wild-type and chimeric beta subunits of
      neuronal nicotinic receptors.
AB  - We have studied the voltage-jump relaxation currents for a series of neuronal
      nicotinic acetylcholine receptors resulting from the coexpression of wild-type
      and chimeric beta 4/beta 2 subunits with alpha 3 subunits in Xenopus oocytes.
      With acetylcholine as the agonist, the wild-type alpha 3 beta 4 receptors
      displayed five- to eightfold slower voltage-jump relaxations than did the wild
      type alpha 3 beta 2 receptors. In both cases, the relaxations could best be
      described by two exponential components of approximately equal amplitudes over a
      wide range of [ACh]'s. Relaxation rate constants increased with [ACh] and
      saturated at 20- to 30-fold lower concentrations for the alpha 3 beta 2 receptor
      than for the alpha 3 beta 4 receptor, as observed previously for the peak steady
      state conductance. Furthermore, the chimeric beta 4/beta 2 subunits showed a
      transition in the concentration dependence of the rate constants in the region
      between residues 94 and 109, analogous to our previous observation with steady
      state conductances. However, our experiments with a series of beta-subunit
      chimeras did not localize residues that govern the absolute value of the kinetic
      parameters. Hill coefficients for the relaxations also differed from those
      previously measured for steady state responses. The data reinforce previous
      conclusions that the region between residues 94 and 109 on the beta subunit plays
      a role in binding agonist but also show that other regions of the receptor
      control gating kinetics subsequent to the binding step.

PMID- 8868049
TI  - A recombinant inwardly rectifying potassium channel coupled to GTP-binding
      proteins.
AB  - GTP-binding (G) proteins have been shown to mediate activation of inwardly
      rectifying potassium (K+) channels in cardiac, neuronal and neuroendocrine cells.
      Here, we report functional expression of a recombinant inwardly rectifying
      channel which we call KGP (or hpKir3.4), to signify that it is K+ selective, G
      protein-gated and isolated from human pancreas. KGP expression in Xenopus oocytes
      resulted in sizeable basal (or agonist-independent) currents while coexpression
      with a G-protein-linked receptor, yielded additional agonist-induced currents.
      Coexpression of KGP and hGIRK1 (a human brain homolog of GIRK1/Kir3.1) produced
      much larger basal currents than those observed with KGP or hGIRK1 alone, and upon
      coexpression with receptor, similarly large agonist-induced currents could be
      obtained. Pertussis toxin treatment significantly diminished agonist-dependent
      currents due to either KGP or KGP/hGIRK1 expression. Interestingly, PTX also
      significantly reduced basal KGP or KGP/hGIRK1 currents, suggesting that basal
      activity is largely the result of G-protein gating as well. When the two channels
      were coexpressed with receptor, the relative increase in current elicited by
      agonist was similar whether KGP and hGIRK1 were expressed alone or together. When
      in vitro translated or when expressed in Xenopus oocytes or CHO mammalian cells,
      KGP gave rise to a nonglycosylated 45-kD protein. Antibodies directed against
      either KGP or hGIRK1 coprecipitated both proteins coexpressed in oocytes,
      providing evidence for the heteromeric assembly of the two channels and
      suggesting that the current potentiation seen with coexpression of the two
      channel subunits is due to specific interactions between them. An endogenous
      oocyte protein similar in size to KGP was also coprecipitated with hGIRK1.

PMID- 8868050
TI  - Interaction of internal Ba2+ with a cloned Ca(2+)-dependent K+ (hslo) channel
      from smooth muscle.
AB  - We have studied potassium currents through a cloned Ca(2+)-dependent K+ channel
      (hslo) from human myometrium. Currents were recorded in inside-out macropatches
      from membranes of Xenopus laevis oocytes. In particular, the inactivation-like
      process that these channels show at high positive potentials was assessed in
      order to explore its molecular nature. This current inhibition conferred a bell
      shape to the current-voltage curves. The kinetic and voltage dependence of this
      process suggested the possibility of a Ba2+ block. There were the following
      similarities between the inactivation process observed at zero-added Ba2+ and the
      internal Ba2+ block of hslo channels: (a) in the steady state, the voltage
      dependence of the current inhibition observed at zero-added Ba2+ was the same as
      the voltage dependence of the Ba2+ block; (b) the time constant for recovery from
      current decay at zero-added Ba2+ was the same as the time constant for current
      recovery from Ba2+ blockade; and (c) current decay was largely suppressed in both
      cases by adding a Ba2+ chelator [(+)-18-crown-6-tetracarboxylic acid] to the
      internal solution. In our experimental conditions, we determined that the Kd for
      the complex chelator-Ba2+ is 1.6 x 10(-10) M. We conclude that the current decay
      observed at zero-added Ba2+ to the internal solution is due to contaminant Ba2+
      present in our solutions (approximately 70 nM) and not to an intrinsic gating
      process. The Ba2+ blocking reaction in hslo channels is bimolecular. Ba2+ binds
      to a site (Kd = 0.36 +/- 0.05 mM at zero applied voltage) that senses 92 +/- 25%
      of the potential drop from the internal membrane surface.

PMID- 8868051
TI  - Assembly and suppression of endogenous Kv1.3 channels in human T cells.
AB  - The predominant K+ channel in human T lymphocytes is Kv1.3, which inactivates by
      a C-type mechanism. To study assembly of these tetrameric channels in Jurkat, a
      human T-lymphocyte cell line, we have characterized the formation of
      heterotetrameric channels between endogenous wild-type (WT) Kv1.3 subunits and
      heterologously expressed mutant (A413V) Kv1.3 subunits. We use a kinetic analysis
      of C-type inactivation of currents produced by homotetrameric channels and
      heterotetrameric channels to determine the distribution of channels with
      different subunit stoichiometries. The distributions are well-described by either
      a binomial distribution or a binomial distribution plus a fraction of WT
      homotetramers, indicating that subunit assembly is a random process and that
      tetramers expressed in the plasma membrane do not dissociate and reassemble.
      Additionally, endogenous Kv1.3 current is suppressed by a heterologously
      expressed truncated Kv1.3 that contains the amino terminus and the first two
      transmembrane segments. The time course for suppression, which is maximal at 48 h
      after transfection, overlaps with the time interval for heterotetramer formation
      between heterologously expressed A413V and endogenous WT channels. Our findings
      suggest that diversity of K+ channel subtypes in a cell is regulated not by
      spatial segregation of monomeric pools, but rather by the degree of temporal
      overlap and the kinetics of subunit expression.

PMID- 8868052
TI  - Block of single L-type Ca2+ channels in skeletal muscle fibers by aminoglycoside
      antibiotics.
AB  - The activity of single L-type Ca2+ channels was recorded from cell-attached
      patches on acutely isolated skeletal muscle fibers from the mouse. The
      experiments were concerned with the mechanism by which aminoglycoside antibiotics
      inhibit ion flow through the channel. Aminoglycosides produced discrete
      fluctuations in the single-channel current when added to the external solution.
      The blocking kinetics could be described as a simple bimolecular reaction between
      an aminoglycoside molecule and the open channel. The blocking rate was found to
      be increased when either the membrane potential was made more negative or the
      concentration of external permeant ion was reduced. Both of these effects are
      consistent with a blocking site that is located within the channel pore. Other
      features of block, however, were incompatible with a simple pore blocking
      mechanism. Hyperpolarization enhanced the rate of unblocking, even though an
      aminoglycoside molecule must dissociate from its binding site in the channel
      toward the external solution against the membrane field. Raising the external
      permeant ion concentration also enhanced the rate of unblocking. This latter
      finding suggests that aminglycoside affinity is modified by repulsive
      interactions that arise when the pore is simultaneously occupied by a permeant
      ion and an aminoglycoside molecule.

PMID- 8868054
TI  - Adrenergic regulation of haematopoiesis.
AB  - In spite of many reports demonstrating the presence of sympathetic fibres
      innervating the bone marrow, the evidence for a direct adrenergic influence on
      haematopoiesis is a recent finding. This review concentrates on recent work on
      the role of adrenergic agents in haematopoiesis. In particular, alpha-adrenergic
      antagonists may greatly augment myelopoiesis and platelets production while
      decreasing lymphopoiesis either after bone marrow transplantation or in normal
      mice. On the other hand, adrenergic agonists seem to exert an inhibitory effect
      on myelopoiesis. Of clinical relevance, the sympathetic neurotransmitter
      noradrenaline can rescue the blood forming system and improve the survival of
      mice injected with a lethal dose of carboplatin or exposed to X-ray irradiation.
      Apparently, noradrenaline acts via alpha 1-adrenergic receptors present in pre-B
      cells. Activation of such receptors seems to induce the production of
      transforming growth factor-beta which mediates the haematopoietic effects. These
      findings seems relevant to our understanding of the physiopathology of
      haematopoiesis and may open new possibilities for treating haematological
      disorders and in the clinical management of anticancer myeloablative treatments.

PMID- 8868053
TI  - Subconductance block of single mechanosensitive ion channels in skeletal muscle
      fibers by aminoglycoside antibiotics.
AB  - The activity of single mechanosensitive channels was recorded from cell-attached
      patches on acutely isolated skeletal muscle fibers from the mouse. The
      experiments were designed to investigate the mechanism of channel block produced
      by externally applied aminoglycoside antibiotics. Neomycin and other
      aminoglycosides reduced the amplitude of the single-channel current at negative
      membrane potentials. The block was concentration-dependent, with a half-maximal
      concentration of approximately 200 microM. At high drug concentrations, however,
      block was incomplete with roughly one third of the current remaining unblocked.
      Neomycin also caused the channel to fluctuate between the open state and a
      subconductance level that was also roughly one third the amplitude of the fully
      open level. An analysis of the kinetics of the subconductance fluctuations was
      consistent with a bimolecular reaction between an aminoglycoside molecule and the
      open channel (kon = approximately 1 x 10(6) M-1s-1 and koff = approximately 400 s
      1 at -60 mV). Increasing the external pH reduced both the rapid block of the open
      channel and the frequency of the subconductance fluctuations, as if both blocking
      actions were produced by a single active drug species with a pKa = approximately
      7.5. The results are interpreted in terms of a mechanism in which an
      aminoglycoside molecule partially occludes ion flow through the channel pore.

PMID- 8868055
TI  - Ultrastructural and spectroscopic methods in the study of anthracycline-membrane
      interaction.
AB  - Observations on the interaction of anthracycline antibiotics with the plasma
      membrane, performed by morphological, ultrastructural, microanalytical and
      spectroscopic methods, are reported and discussed in this review. Scanning and
      transmission electron microscopy analysis indicates that doxorubicin (DOX)
      induces dose-dependent modifications of the cell morphology and membrane
      ultrastructure of human erythrocytes. The formation of intramembrane particle
      free domains on both the fracture faces of the plasma membrane suggests that the
      DOX molecules become incorporated within the lipid bilayer. Electron energy-loss
      spectroscopy measurements reveal a reduction in the P/C ratio in treated
      membranes, probably due to a phospholipid "dilution" following the incorporation
      of DOX molecules. The radiowave dielectric spectroscopy indicates modifications
      induced by DOX in the passive electrical properties of the membrane. In
      particular, the decrease in membrane conductivity suggests that the interaction
      of the drug with the membrane lipids can affect the function of specific ion
      channels. The results obtained allow us to propose a structural model of the DOX
      membrane interaction, in which DOX molecules self-associate in the phospholipid
      bilayer. The DOX incorporation induces remarkable changes in the structural and
      functional properties of the plasma membrane, strengthening the hypothesis that
      this drug can also exert its cytotoxic action at the membrane level.

PMID- 8868056
TI  - Lipid peroxide, phospholipids, glutathione levels and superoxide dismutase
      activity in rat brain after ischaemia: effect of ginkgo biloba extract.
AB  - The influence of ginkgo biloba extract on the lipid peroxide product
      (malondialdehyde, MDA), glutathione (GSH) and phospholipids levels as well as
      superoxide dismutase (SOD, 1.15.1.1) and lactate dehydrogenase (LDH, 1.1.1.27)
      activities in rat brain after occlusion of common carotid arteries was
      investigated. Two experimental models were studied: 60 min ischaemia without
      reperfusion and 60 min ischaemia followed by 60 min reperfusion. Compared to sham
      operated animals, ischaemia followed by reperfusion increased cytosolic LDH
      activity and mitochondrial lipid peroxide content and decreased the superoxide
      dismutase activity and mitochondrial total phospholipids level. Preischaemic
      administration of ginkgo biloba extract (150 mg kg-1, p.o.) could normalize the
      SOD activity of the rat brain. The extract was also able to reduce the lipid
      peroxide and phospholipids contents of the mitochondrial rat brain. These effects
      could be explained on the basis of the antioxidant property of ginkgo biloba
      extract and suggests its beneficial role in the protection against post-ischaemic
      injury.

PMID- 8868057
TI  - Lipid peroxidation and lysosomal integrity in different inflammatory models in
      rats: the effects of indomethacin and naftazone.
AB  - In the present study, the potential involvement of lipid peroxidation and
      disruption of lysosomal integrity in the pathogenesis of different experimental
      models of inflammation was examined. The chosen models were carrageenan-induced
      paw oedema, carrageenan granuloma pouch (acute phase) and Freund's adjuvant
      induced arthritis in rats. The pharmacological and biochemical effects of
      naftazone, a lysosomal membrane stabilizer and indomethacin, a standard anti
      inflammatory agent were evaluated with regard to paw oedema volume, serum and
      exudate activities of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG),
      in addition to serum and liver lipid peroxide (LP) levels. Intraperitoneal
      administration of the test drugs, in rats subjected to inflammation, produced:
      (1) a significant inhibition of carrageenan-induced paw oedema, (2) a marked
      reduction of the paw oedema of the Freund's adjuvant arthritis animals, (3) a
      remarkable decrease of lysosomal leakage of NAG into the exudate of carrageenan
      granuloma pouch, (4) a slight, but significant, reduction of NAG activity in the
      serum of rats subjected to carrageenan inflammation, and (5) a reduction of the
      serum level of LP that was elevated in adjuvant-induced arthritic rats. The level
      of liver LP was altered by either drugs in an opposite manner; while naftazone
      lowered hepatic LP, indomethacin markedly elevated its level. The results of the
      present investigation revealed that lipid peroxidation and disruption of
      lysosomal integrity are implicated in the pathogenesis of inflammatory processes,
      and the protection against these deleterious effects imparted both drugs
      significant anti-inflammatory activity.

PMID- 8868058
TI  - Investigation of the effects of moclobemide in chronic ethanol feeding rats.
AB  - Effects of chronic moclobemide administration on ethanol consumption, blood
      ethanol level, motor coordination and seizures induced by an audiogenic stimulus
      during ethanol withdrawal syndrome have been investigated in chronically ethanol
      intoxicated rats. Adult male Wistar rats (211-289 g) were used. Ethanol (7.2%
      v/v) was given to rats by a special liquid diet for 15 days. Moclobemide (10, 30
      and 45 mg kg-1) or saline was injected to ethanol-feeding rats subcutaneously
      through 15 days. Daily ethanol intake and body weight gain of the rats were
      recorded. Blood ethanol levels were measured in rats given saline or chronic
      moclobemide (30 mg kg-1) just before and 6 h after ethanol withdrawal. At the
      sixth hour of the ethanol withdrawal, the incidence, intensity and latency of the
      seizures induced by an audiogenic stimulus were recorded in saline and acute (30
      mg kg-1) or chronic (10, 30 and 45 mg kg-1) moclobemide-administered rats.
      Accelerod performances of the chronic moclobemide (45 mg kg-1) or saline injected
      rats were also evaluated. The mean ethanol intake of the rats ranged from 10.06
      to 15.63 g kg-1 day-1 during the study. Chronic moclobemide treatment did not
      occur any significant effect on daily ethanol consumption, ethanol clearance and
      accelerod performances of the rats. No significant changes on the incidence,
      intensity and the latency of the audiogenic seizures were also observed. Our
      results suggest that there has been no adverse interaction between ethanol and
      moclobemide.

PMID- 8868059
TI  - The antiopioid peptide, neuropeptide FF, enhances the effects of acute morphine
      on the cerebral monoamines in rats.
AB  - The effects of neuropeptide FF (NPFF) on the changes induced by acute morphine in
      cerebral monoamines were studied in male Wistar rats. We measured the
      concentrations of noradrenaline (NA), 5-hydroxytryptamine (5-HT), dopamine and
      their main metabolites in the limbic area (LIM), hypothalamus (HYP) and lower
      brain stem (LBS). NPFF 10 micrograms x 3 at 20 min intervals, i.c.v.,
      bilaterally) did not alter the concentrations of monoamines or their metabolites.
      Morphine (10 mg kg-1, s.c., 1 h) did not alter NA or 5-HT or their metabolites in
      any brain area studied, but elevated 3,4-dihydroxyphenylacetic acid (DOPAC)
      and/or homovanillic acid (HVA) in LIM and HYP. Combination of morphine and NPFF
      decreased NA in LIM, elevated 3-methoxy-4-hydroxyphenylethylene glycol in HYP and
      LBS as well as 5-hydroxyindoleacetic acid in LIM and HYP. These responses are
      typical to morphine at doses larger than 10 mg kg-1, and suggest a synergistic
      effect of the two compounds. Further, the morphine-induced elevations of DOPAC
      and HVA were potentiated by NPFF in LIM and HYP. In conclusion, our results
      suggest that NPFF does not attenuate but rather enhances the changes induced by
      acute morphine in the cerebral monoamines.

PMID- 8868060
TI  - Flumazenil, diazepam, nordiazepam and oxazepam interactions on plasma protein
      binding.
AB  - The effect of flumazenil (FLU) on plasma protein binding of diazepam (DZ),
      nordiazepam (ND) and oxazepam (OX) was determined in plasma from drug-naive dogs
      to which graded concentrations of tested drugs alone and in combination were
      added. The results revealed that as the concentration of FLU added to plasma
      alone was increased its binding with plasma proteins decreased and that there
      were no significant binding interactions between FLU and OX, ND and DZ.

PMID- 8868061
TI  - Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors
      in C2C12 myotubes.
AB  - Three days of treatment with the glucocorticoid dexamethasone (1 nM-1 microM)
      induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine
      receptor (nAChR) in C2C12 mouse myotubes (EC50 = 10 +/- 7.3 nM), as assessed by
      [3H]alpha-BuTx binding. The maximum increase in binding amounted 148 +/- 17.6% of
      control. Parallel electrophysiological measurements employed the patch-clamp
      technique in cell-attached configuration. The nAChR single channel properties
      were investigated in the presence of carbachol (1 microM) in the pipette.
      Treatment with dexamethasone (1 microM, 1-5 days) induced an increase in the
      number of patches showing channel activity from 30 to 70%. Ion channel
      characteristics did not differ significantly in control and dexamethasone treated
      myotubes. Conductance was 32 +/- 3 vs 31 +/- 2 pS, respectively. The time
      constants of open time events tau 1 and tau 2 were 0.6 +/- 0.1 and 6.6 +/- 1 ms
      vs 0.6 +/- 0.1 and 6.6 +/- 1 ms, respectively. Closed duration's tau 1 and tau 2
      were 1.1 +/- 0.2 and 110 +/- 12 ms vs 1.2 +/- 0.3 and 107 +/- 18 ms. In
      conclusion, dexamethasone upregulated nAChRs are functional and their
      electrophysiological parameters are similar to those found in control myotubes.

PMID- 8868062
TI  - Toxic effects of the novel protein UpI from the sea anemone Urticina piscivora.
AB  - UpI is a basic protein, with molecular mass (approximately 28 kDa) and a pI >
      9.4, isolated from the sea anemone Urticina piscivora. It is a potent cardiac
      stimulatory protein with the partial amino acid sequence
      D1ENEN5LYGPN10ENKAK15AKDLT20AGASY25LTKEA30GCTKL35QAGCT40MYQAY45N [1]. The toxic
      effects of UpI and the crude extract from which it was isolated have been
      investigated on three tumour cell lines: KB, L1210, and HEL 299 cells. UpI,
      however, was less potent on each cell line than the crude extract. Since previous
      experiments had shown extracts of U. piscivora to be haemolytic on erythrocytes
      of rat, guinea pig and dog, the haemolytic action of UpI was investigated. It was
      found to be a potent haemolysin on erythrocytes of rat, guinea pig, dog, pig and
      human, causing haemolysis on erythrocytes of each species tested at
      concentrations as low as 10(-10) M. Haemolysis was inhibited in a concentration
      dependent manner by the phospholipid sphingomyelin but not cholesterol. Using
      scanning electron microscopy, it is now being shown that UpI produces significant
      structural damage to membranes of erythrocytes from rat and guinea pig. It proved
      to be a potent ichthyotoxin. These data suggest that sea anemone toxin not only
      possess different pharmacological activities but that UpI, one of the active
      constituents, could be responsible for the different pharmacological effects
      exhibited by the crude extract.

PMID- 8868064
TI  - Cystatins in health and disease.
AB  - Proteolytic enzymes have many physiological functions in plants, bacteria,
      viruses, protozoa and mammals. They play a role in processes such as food
      digestion, complement activation or blood coagulation. The action of proteolytic
      enzymes is biologically controlled by proteinase inhibitors and increasing
      attention is being paid to the physiological significance of these natural
      inhibitors in pathological processes. The reason for this growing interest is
      that uncontrolled proteolysis can lead to irreversible damage e.g. in chronic
      inflammation or tumor metastasis. This review focusses on the possible role of
      the cystatins, natural and specific inhibitors of the cysteine proteinases, in
      pathological processes.

PMID- 8868063
TI  - Correlation between reduction of surface hydrophobicity of S. aureus and the
      decrease in its adhesiveness induced by subinhibitory concentrations of
      brodimoprim.
AB  - Hydrophobic interactions are involved in the mechanism of adhesion of a variety
      of bacteria to host tissues. Bacterial attachment to human cells is modulated by
      a change in interfacial free energy and this is correlated with surface
      hydrophobicity of bacterial cells. In S. aureus (one ATCC25923+four clinical
      isolates) hydrophobicity before and after incubation with subinhibitory
      concentrations (sub-MICs) of brodimoprim (BMP), a dimethyoxypyrimidine recently
      entered clinical practice, was measured by sessile drop technique as the contact
      angle. BMP is a new molecule derived from trimethoprim by substitution of the
      OCH3 group in position 4 of the benzyl-ring with a bromine atom. Bacterial
      adhesiveness of the same S. aureus strains was measured under the same
      experimental conditions. BMP significantly decreased the surface hydrophobicity
      of S. aureus strains at one-half MIC and one-quarter MIC. At sub-MICs
      concentrations BMP also reduced the adhesiveness to human epithelial buccal cells
      but this effect was significant down to one-sixteenth MIC. The two phenomena are
      correlated and hydrophobicity is involved in bacterial adhesiveness but the
      molecular mechanisms for the two phenomena do not completely overlap, with
      adhesiveness the more complex and based on a system involving both the bacteria
      and the epithelial cells with their specific surface characteristics.

PMID- 8868065
TI  - Repeat-induced gene silencing: common mechanisms in plants and fungi.
AB  - One of the most surprising observations made in plant science in recent years is
      the inactivation of transgenes triggered by interactions between DNA repeats. In
      plants, we can differentiate between transcriptional silencing, most likely
      reflecting a regulation at the DNA level, and post-transcriptional silencing that
      affects steady state RNA levels. In the filamentous fungi Ascobolus immersus and
      Neurospora crassa, we find two premeiotic silencing processes that are also based
      on the interaction of repeated sequences. A common feature of transcriptional
      silencing in plants and premeiotic gene inactivation in filamentous fungi is that
      the repeated sequences undergo cytosine methylation. DNA methylation, which is
      either the cause or the consequence of gene silencing, can be associated with
      changes in chromatin structure. These structural changes are reminiscent of
      homology-based silencing mechanisms in Drosophila, an organism that lacks DNA
      methylation. Repeat-induced silencing may therefore reflect the activity of an
      endogenous mechanism, present in some species, which screens for homology and has
      significant implications for the organization and evolution of the genome.

PMID- 8868066
TI  - Human Immunodeficiency Virus type 1 reverse transcriptase.
AB  - The Human Immunodeficiency Virus type 1 (HIV-1) is a retrovirus and a causative
      agent of the Acquired Immuno Deficiency Syndrome (AIDS). Retroviruses are
      distinct from other viruses in their ability to encode an enzyme called reverse
      transcriptase (RT). The RT is the enzyme mainly involved in replication. It
      performs RNA- as well as DNA-dependent DNA synthesis in order to convert the
      single-stranded viral RNA genome into double-stranded DNA. The double-stranded
      DNA is stably integrated into the host cell genome and is used as a template for
      the production of a new viral generation. The HIV-1 RT is partially encoded by
      the POL open reading frame of the HIV-1 genome and consists of two subunits of 66
      kDa (p66) and 51 kDa (p51). The p66 polypeptide encodes the reverse transcriptase
      and the RNase H domain. Half of the p66 molecules are further processed to
      generate the p51 protein with an identical N-terminus, but lacking the C-terminus
      which encodes the RNase H domain. In vivo both polypeptides are found in
      equimolar amounts thus forming a heterodimer. This dimerization is critical for
      the enzymatic activity. In this review we summarize (i) the replication cycle of
      HIV-1, (ii) the enzymatic properties of HIV-1 RT and (iii) the structure-function
      relationship of the HIV-1 RT in view of the known three dimensional structure.

PMID- 8868067
TI  - Influence of ochratoxin A treatment on the activity of membrane bound enzymes in
      rat brain regions.
AB  - Ochratoxin A is a mycotoxin produced by Aspergillus ochraceus and is a natural
      contaminant of mouldy food. We examined the neuroactive potential of ochratoxin A
      by measuring the changes in the activities of several membrane bound, cytoplasmic
      and lysosomal enzymes in the brain of adult female rats, following subchronic
      application of ochratoxin A. The activities of both soluble and membrane bound
      fractions of ecto-5'nucleotidase, ecto-Ca2+/Mg2+ATPase, alanine aminopeptidase,
      gamma-glutamyl transferase, as well as activities of lactate dehydrogenase and of
      N-acetyl-beta-D-glucosaminidase were followed. Biochemical effects were examined
      in cerebral cortex, cerebellum and hippocampus. The results obtained showed
      physiologically significant alterations in the activity of enzymes tested. The
      changes were found to be time-dependent and regionally selective. Compared to
      controls, statistically significant increases in gamma-glutamyl transferase were
      observed in all three brain regions, while in the case of alanine aminopeptidase
      activities differed with regard to region, the highest increase being observed in
      hippocampus. Ecto-Ca2+/Mg2+ATPase and ecto-5'nucleotidase showed distinct changes
      lasting for 20 days of treatment, while increase in the activities of N-acetyl
      beta-D-glucosaminidase and lactate dehydrogenase were visible only at the
      beginning of the treatment. By the end of the trial the activities of almost all
      enzymes returned back to normal values.

PMID- 8868068
TI  - Determination of choline dehydrogenase activity along the rat nephron.
AB  - A radioenzymatic microassay was developed to quantitate choline dehydrogenase
      activity in single microdissected nephron segments. This enzyme is the rate
      limiting step in the biosynthesis of betaine, which serves as an intracellular
      osmoregulatory organic solute in mammalian kidney. The enzyme localized in renal
      mitochondrial inner membrane forms betaine aldehyde, which in the assay is
      converted to betaine by oxidative treatment. A histochemical procedure based on
      the formazan detection of tetranitroblue tetrazolium chloride was applied in
      parallel. The results show that activities in proximal convoluted and straight
      tubules are more than 5 times higher (21 to 25 pmol h-1 mm tubule-1) compared to
      distal nephron segments with no significant differences along the proximal
      tubule. Along the osmotic gradient from the outer medullary towards the papillary
      structures enzyme activities increased in ascending limbs of Henle's loop and
      collecting tubules. Collecting ducts showed two times higher activities than
      ascending loop segments when corrected for tubular cell volumes. The quantitative
      data were confirmed by the histochemical procedure. The results allow for the
      conclusion that betaine synthesis is sufficient to build up renal betaine, but
      cannot explain the distribution pattern of betaine along the corticopapillary
      axis. Additional mechanisms like intrarenal and tubular transport have to be
      postulated.

PMID- 8868070
TI  - Platypus insulin: indications from the amino acid sequence of significant
      differences in structure from porcine insulin.
AB  - Insulin from a monotreme, the platypus (Ornithorhynchus anatinus), was isolated
      and the amino acid sequence determined. It differs from pig insulin at eleven
      amino acid sites, mainly on the surface of the monomer. Substitutions relative to
      pig insulin occur in the monomer-monomer interface, the dimer-dimer interface and
      the receptor binding region. The residues A5 Glu, A8 Lys and A13 Met have not
      been reported before in any insulin. Multiple sequence comparison studies reveal
      a relatively close relationship with the nearest group of relatives to the
      platypus, the mammals. The relationship of the platypus sequence to reptilian
      insulin sequences (and amphibian and avian insulin sequences in this case) is
      sufficiently close to support the observation that platypus has retained some
      ancient reptilian characteristics over the course of evolution. Model building
      the platypus insulin sequence on the structure of porcine insulin indicates that
      there may be some interesting differences.

PMID- 8868069
TI  - Cloning and characterization of the murine B-cell specific transcriptional
      coactivator Bob1.
AB  - From a murine B-cell cDNA-library we have cloned a cDNA encoding the murine B
      cell specific coactivator mBob1. The protein is the murine homologue to the
      recently described human coactivator Bob1 (hBob1), also referred to as OBF-1 or
      OCA-B. We have also characterized the genomic mBob1 clone. Analysis of its intron
      exon structure has allowed identification of a C-terminal splice variant. mBob1
      is B-cell restricted, and is found in all B-cell lines representing different
      stages of B-cell differentiation. mBob1 interacts with the octamer transcription
      factors Oct-1 and Oct-2 and stimulates transcription mediated by these factors.

PMID- 8868071
TI  - Early effects of high doses of retinol (vitamin A) on the in situ cellular
      metabolism in rat liver.
AB  - Understanding of the possible toxicity associated with hypervitaminosis A becomes
      increasingly important in view of the popularity of vitamin A supplementation.
      Hypervitaminosis A for many years may eventually lead to hepatocellular damage.
      In the present study, rats were treated for 7 days with high doses of retinol to
      study the early effects on the metabolism of different types of liver cells using
      (enzyme) histochemistry, immunohistochemistry and electron microscopy. Excessive
      intake of vitamin A activates Kupffer cells and induces accumulation of lipid
      droplets in fat-storing cells as well as proliferation of these cells. Moreover,
      it affects the metabolic heterogeneity in the liver lobules, but does not lead to
      apparent cell damage. Based on the changes in marker enzymes for different
      metabolic processes, it is concluded that the capacity for breakdown of purines,
      the antioxidant capacity, the potential for phagocytosis and the regulation of
      ammonia levels were largely decreased. Increased alkaline phosphatase activity in
      hepatocytes pointed to an activated process of transport of retinol esters over
      the bile canalicular membrane. The possible causes of these metabolic changes
      have been described in the discussion.

PMID- 8868072
TI  - Gastric and colonic inflammatory and vasoactive mediators in experimental portal
      hypertension.
AB  - Rats with portal hypertension and experimental liver disease may exhibit
      increased susceptibility of the gastric mucosa to damage by noxious agents, and
      increased bacterial translocation through the bowel wall. The aim of this study
      was to determine mucosal gastric and colonic generation of vasoactive substances,
      because they may contribute to the altered mucosal function. Rats with partial
      vein ligation (n = 7), complete bile duct ligation (n = 6) and sham-operated rats
      (n = 10) were studied. Three weeks following surgery rats were anesthetized,
      splenic pulp pressure was measured, stomachs and colons were removed and mucosa
      was extracted for determination of prostaglandin E2, thromboxane B2, leukotriene
      B4, leukotriene C4 and endothelin-1 by radioimmunoassay (ng/g) and platelet
      activating factor activity (pg/10 mg) by platelet aggregation. Pulp pressure was
      > 13 mmHg in partial vein ligated rats and bile duct ligated rats and 6 mmHg in
      sham-operated rats. No macroscopic or microscopic lesions were seen any of the
      removed tissues. Gastric mucosal prostaglandin E2 and thromboxane B2 generation
      were decreased by 35% and 7%, respectively, in bile duct ligated rats (bile duct
      ligated versus sham-operated, p < 0.05 for prostaglandin E2 and thromboxane B2).
      Gastric leukotriene B4 and C4 generation, platelet activating factor activity and
      endothelin-1 content did not differ significantly among the three groups. A
      different pattern of changes was observed in the colon. Colonic leukotriene B4
      generation and endothelin-1 content were increased in bile duct ligated rats by
      105% and 210%, respectively (bile duct ligated versus sham-operated, p < 0.05 for
      leukotriene B4 and endothelin-1). The decreased gastric mucosal prostaglandin E2
      generation of bile duct ligated rats may render the gut mucosa of these animals
      relatively ischemic and vulnerable to damage by noxious agents. The increased
      colonic leukotriene B4 generation and the increased endothelin-1 content of the
      colonic mucosa of bile duct ligated rats may promote inflammatory and ischemic
      changes in the colonic mucosa and may enable bacterial translocation.

PMID- 8868073
TI  - Biochemical and clinical study of muscle atrophy at thenar and hypothenar
      eminences in patients with cirrhosis.
AB  - The results of various biochemical examinations in 14 patients with cirrhosis (6
      males and 8 females) with muscle atrophy at the thenar and hypothenar eminence
      (muscle atrophy group; mAG) were compared with those in 13 patients (8 males and
      5 females) with cirrhosis without muscle atrophy at these sites (non-muscle
      atrophy group; NmAG). All patients were elderly men and women (mAG and NmAG, mean
      age, 69 +/- 3 years and 60 +/- 7, respectively). In most mAG patients, muscle
      atrophy was accompanied by palmar erythema. Muscle atrophy was histologically
      demonstrated by biopsy. Furthermore, electromyography and magnetic resonance
      study of the cervical spinal cord revealed that the atrophy was of myogenic
      rather than neurogenic origin. The Child-Pugh score, body mass index and sex
      hormone level in urine (total 24 h) in the two groups were compared along with
      the biochemical results. There were no significant differences between the two
      groups in urine estrogen and testosterone levels. The urinary creatinine
      excretion was significantly reduced in mAG. The creatine phosphokinese, lactate
      dehydrogenase isoenzyme and aldolase levels in serum did not differ significantly
      in the two groups, whereas the serum albumin level was significantly increased in
      NmAG. Significant differences were observed only for the serum albumin level, age
      and body mass index. Thus, we consider that palmar muscle atrophy in patients
      with cirrhosis is not due to hormonal excess in serum, but may be attributable to
      advanced age and diminished physical strength.

PMID- 8868074
TI  - Genotype, serum level of hepatitis C virus RNA and liver histology as predictors
      of response to interferon-alpha 2a therapy in Japanese patients with chronic
      hepatitis C.
AB  - To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes,
      alanine aminotransferase and histology correlate with subsequent response to
      interferon-alpha therapy or not, serum HCV-RNA levels and genotype were
      determined by branched DNA signal amplification assay and genotype-specific
      polymerase chain reaction in 43 patients with chronic active hepatitis C.
      Response to recombinant interferon-alpha 2a (504 million units in total) was
      defined as complete and sustained CR-->SR, n = 12), complete response followed by
      relapse (CR-->Rel, n = 17), and no response (NR, n = 10), excluding dropouts (n =
      4). Patients who showed CR-->SR had a lower HCV-RNA level (0.438 x 10(6) eq/ml)
      compared to CR-->Rel (2.452 x 10(6) eq/ml, p = 0.008) and NR (4.882 x 10(6)
      eq/ml, p = 0.009). A higher proportion of patients with CR-->SR had type 2a HCV
      (67%) compared to the CR-->Rel (28%) and the NR (0%). There was a trend for type
      1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no
      correlation between pretreatment HCV-RNA level and alanine aminotransferase.
      However, no relation between pretreatment HCV-RNA level and liver histology was
      observed; a high proportion of patients with CAH2a showed CR-->SR, compared to
      those with CAH2b (p = 0.001). Moreover, the patients with CAH2b who had low level
      hepatitis C virus viremia did not show CR-->SR. These data indicate that pre
      treatment serum HCV-RNA levels, genotype and liver histology are good predictors
      of subsequent response to interferon-alpha therapy in Japanese patients with
      chronic hepatitis C virus infection.

PMID- 8868075
TI  - Antineutrophil cytoplasmic autoantibodies in autoimmune liver and inflammatory
      bowel diseases.
AB  - Perinuclear antineutrophil cytoplasmic autoantibodies have been described in
      inflammatory bowel diseases and in primary sclerosing cholangitis. Because the
      data concerning their occurrence are conflicting, we have used indirect
      immunofluorescence on ethanol-fixed neutrophils to test the sera from a large
      population of 382 patients with various liver and digestive diseases: in
      particular, from 27 patients with primary sclerosing cholangitis, 105 patients
      with autoimmune chronic active hepatitis, 30 patients with primary biliary
      cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the
      perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative
      colitis and 15% in Crohn's disease. They would not be helpful in the differential
      diagnosis between these two inflammatory bowel diseases. Within the group of
      autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies
      were detected in 44% of sera from patients with primary sclerosing cholangitis
      and in 36% of sera from patients with type I autoimmune active hepatitis, but not
      in primary biliary cirrhosis. When primary sclerosing cholangitis was associated
      with an inflammatory bowel disease, the prevalence of these autoantibodies was
      60%. They were 88% specific for primary sclerosing cholangitis and 86% specific
      for type I autoimmune active hepatitis. Despite their moderate sensitivity and
      specificity in primary sclerosing cholangitis, they remain the only serologic
      marker of this autoimmune liver disease. Moreover, they turned out to be a more
      sensitive marker for inflammatory bowel disease with associated primary
      sclerosing cholangitis.

PMID- 8868076
TI  - Effect of diethylmaleate on bile secretion and ultrastructural appearance of
      hepatocytes in normal rats and mutant rats with defective organic anion
      secretion.
AB  - Diethylmaleate is an organic anion secreted into bile as a glutathione conjugate.
      Its transport by the hepatocyte is associated with dilatation of the Golgi
      apparatus and the appearance of small vesicles in the pericanalicular area. It
      has been speculated that the Golgi apparatus could play a role in the
      intracellular transport and/or the biliary canalicular secretion of
      diethylmaleate. The purpose of this work was to determine whether the alterations
      in the Golgi apparatus and the pericanalicular vesicles could mediate the
      canalicular secretion of diethylmaleate. Diethylmaleate biliary secretion and
      diethylmaleate-induced bile flow were measured in Sprague-Dawley rats, and in TR-
      rats which have an inherited defect in the excretion into bile of organic anions,
      including glutathione conjugates. Livers of both Sprague-Dawley and TR-rats were
      examined by electron microscopy, to characterize the changes in intracellular
      organelles. In Sprague-Dawley rats, as previously described, diethylmaleate
      administration was associated with an increase in bile flow, which was parallel
      in time to the secretion into bile of diethylmaleate conjugates. Electron
      microscopic examination of the liver after diethylmaleate administration showed
      dilatation of the Golgi saccules. In contrast, in TR- rats, the increase in bile
      flow and the secretion of diethylmaleate conjugated were nearly absent.
      Nevertheless, electron microscopic examination showed a dilatation of the Golgi
      saccules similar to that observed in Sprague-Dawley rats. TR- rats, in addition
      to the changes in the Golgi apparatus, had marked dilatation of the endoplasmic
      reticulum. These results show that biliary secretion of diethylmaleate conjugates
      was severely impaired in TR- rats, in spite of a dilatation of the Golgi
      apparatus and of the endoplasmic reticulum. We conclude that it is unlikely that
      the alterations in the Golgi apparatus (and the endoplasmic reticulum) induced by
      diethylmaleate play a role in the canalicular secretion of diethylmaleate. We do
      not exclude the possibility that these organelles could play a role in
      intracellular transport of this compound. Alternatively, these alterations could
      be due to a "toxic" effect of diethylmaleate accumulation in hepatocytes.

PMID- 8868077
TI  - Histological changes of the liver in experimental graft-versus-host disease
      across minor histocompatibility barriers. VIII. Role of eosinophil infiltration.
AB  - Although eosinophil infiltrate has been recognized in hepatic graft-versus-host
      disease, its significance in relation to hepatic graft-versus-host disease
      lesions is unknown. In the present study, we analyzed hepatic eosinophil
      infiltration in relation to bile duct damage in experimental mouse graft-versus
      host disease across minor histocompatibility barriers up to 14 months after
      transplantation. Portal eosinophil infiltration was found from 1 week after
      transplantation throughout the entire 14-month observation period. It was most
      striking during the early chronic stage of hepatic graft-versus-host disease
      between 2 to 7 months, with a peak at 5 months after transplantation. Microscopic
      and electron microscopic study revealed eosinophils infiltrated around the bile
      duct as well as in the bile duct epithelial layer. They were commonly found
      together with lymphocytes but were also occasionally found singly around the bile
      duct and in the bile duct epithelial layer. Bile duct epithelial cells in contact
      with and in the vicinity of eosinophils showed a variety of generative changes,
      occasionally associated with the presence of extracellular eosinophil granules.
      Bile duct epithelial cells with eosinophil infiltration just beneath the basement
      membrane frequently showed further characteristic severe degenerative changes
      with shedding or dropping-off into the lumen, which features were quite similar
      to those seen in the bronchial epithelium in asthma patients. These results
      indicate that not only lymphocytes but also eosinophils may be involved in the
      production of the bile duct injury in hepatic graft-versus-host disease,
      especially in its early chronic stage.

PMID- 8868079
TI  - Distribution of hepatitis C virus RNA in the liver and its relation to
      histopathological changes.
AB  - To investigate a cellular mode of HCV-infection in the liver and its pathological
      implications in relation to histopathological changes or clinical data, we
      studied the distribution of HCV-RNA in the livers of 21 patients with HCV-related
      chronic liver disease (chronic active hepatitis, 14 cases; cirrhosis, 7 cases)
      using the in situ hybridization technique. In situ hybridization was performed on
      4% paraformaldehyde-fixed frozen sections with digoxigenin-labeled DNA probe
      deduced from the core region of HC-J4. In situ hybridization showed positive
      signals in the liver specimens of 20/21 cases. The signals were localized in the
      cytoplasm of hepatocytes. The distribution pattern of positive cells was
      individually different, whereas the pattern was identical in the right and left
      lobes. There were no correlations of the HCV-positive cell number with serum
      aminotransferase levels at biopsy or with genotypes of HCV. The positive
      hepatocytes were occasionally associated with infiltrating mononuclear cells, and
      they were sparsely distributed in the area of piecemeal necrosis. These findings
      suggest that factors such as host immunoreaction to the virus may be more
      important than its direct cytopathy in the pathogenesis of chronic hepatitis C
      virus infection.

PMID- 8868078
TI  - Hyaluronate levels in donor organ washout effluents: a simple and predictive
      parameter of graft viability.
AB  - The principal cause of primary non-function in orthotopic liver transplantation
      is thought to be preservation injury to the microvasculature. We, therefore,
      evaluated if effluent levels of hyaluronate, whose uptake is an endothelial cell
      marker, could predict early graft function and ultimate graft outcome in
      orthotopic liver transplantation. A total of 102 cases were studied in two
      phases. In the first phase, we attempted to determine if a correlation existed
      between effluent hyaluronate levels, early graft function and ultimate graft
      outcome. This phase of the study was also used to determine hypothetical cut-off
      values for hyaluronate which could discriminate between good and bad livers.
      Thirty-two livers orthotopically transplanted to randomly selected primary
      recipients were studied. After varying periods of static cold storage (4 degrees
      C) in University of Wisconsin solution, the livers were reinfused with cold (4
      degrees C) lactated Ringer's solution. The first 50 ml of the reperfusion
      effluent was collected from the infrahepatic vena cava. Effluent samples were
      analyzed for hyaluronate. Linear regression analysis demonstrated a significant
      correlation between effluent hyaluronate levels and post-operative aspartate and
      alanine aminotransferase levels (p < 0.001 for both). Logistic regression
      demonstrated a highly significant correlation (p = 0.0056) between effluent
      hyaluronate levels and ultimate graft outcome. Generation of Receiver
      Characteristics Curves indicated that a level between 400 and 430 micrograms.l-1
      could possibly discriminate between good livers and those at risk of early graft
      failure. The authenticity of this hyaluronate cut-off level was further confirmed
      in the second phase of the study where 70 consecutive primary crossmatch-negative
      transplants were performed. A highly significant difference was observed in peak
      aspartate and alanine aminotransferase levels in the first week (p < 0.0006 and p
      < 0.0005, respectively) between livers with effluent hyaluronate levels < or =
      400 micrograms.l-1 and livers with hyaluronate levels higher than 400
      micrograms.l-1. Logistic regression revealed a highly significant correlation
      between effluent hyaluronate levels and graft success (p = 0.0001). Since
      hyaluronate uptake by the microvascular endothelial cell is significantly greater
      than production, high hyaluronate effluent levels in failed livers would be due
      to decreased hyaluronate uptake by the injured microvascular endothelial cell. We
      therefore conclude that effluent hyaluronate levels may prove to be a reliable
      preoperative test to assess early graft function and outcome in clinical
      orthotopic liver transplantation.

PMID- 8868081
TI  - Liver abscesses due to Listeria monocytogenes.
AB  - Involvement of the liver in cases of Listeria monocytogenes is uncommon. We
      report a case of hepatitis due to L. monocytogenes, with a pathological finding
      of multiple abscesses. Blood cultures yielded L. monocytogenes. The patient died
      a few days after admission.

PMID- 8868080
TI  - Structural and functional features of bile canaliculi in adult rat hepatocyte
      spheroids.
AB  - Spheroids of adult rat hepatocytes are spherical cell aggregates which retain
      three-dimensional architecture and hepatocyte specific functions. In this study,
      we investigated the detailed structure and function of bile canaliculi in
      spheroids. Hepatocytes were prepared from adult rat liver and cultured with
      epidermal growth factor (50 ng/ml). Hepatocytes formed floating spheroids 4 days
      after inoculation. The morphology of hepatocyte spheroids was investigated after
      fluorescent staining for actin using confocal laser scanning microscopy and
      electron microscopy. To study the function of bile canaliculi, the transcellular
      transport of fluorescein diacetate was observed. These experiments were performed
      in a control group and in a group treated with the actin inhibitor cytochalasin
      B. In a control group, spheroids contained bile canalicular structures which were
      surrounded by actin filaments. Added fluorescent dye was secreted and pooled in
      bile canaliculi. Cytochalasin B caused marked distention of bile canaliculi and
      prominent accumulation of secreted fluorescent dye in dilated bile canaliculi.
      This phenomenon was based on the impairment of contractile movement of bile
      canaliculi. These results demonstrate that hepatocyte spheroids maintain
      functional and morphological peculiarity, and therefore this model may be useful
      in investigation of the mechanism of bile formation and intrahepatic cholestasis.

PMID- 8868082
TI  - Understanding replication mechanisms in viroids and viroidlike RNAs.

PMID- 8868083
TI  - EBNA1 and E2: a new paradigm for origin-binding proteins?

PMID- 8868084
TI  - The interplay of herpesviruses in AIDS: superantigen sharing.

PMID- 8868085
TI  - Cytotoxic T cells: more weapons for new targets?

PMID- 8868086
TI  - Does immunity to tuberculosis contribute to pathogenesis?

PMID- 8868087
TI  - The role of pheromones in bacterial interactions.

PMID- 8868088
TI  - The contribution of pneumolysin to the pathogenicity of Streptococcus pneumoniae.

PMID- 8868089
TI  - Subversion of the MHC class I antigen-presentation pathway by adenoviruses and
      herpes simplex viruses.

PMID- 8868090
TI  - Characterization of the Mycobacterium tuberculosis phagosome.

PMID- 8868091
TI  - Is the DNA repair system involved in hepatitis-B-virus-mediated hepatocellular
      carcinogenesis?

PMID- 8868092
TI  - Leukemia.

PMID- 8868093
TI  - Biology and treatment of acute promyelocytic leukemia.
AB  - Recent progresses made in the biology of acute promyelocytic leukemia and
      therapeutic improvements obtained in acute promyelocytic leukemia since the
      advent of all-trans retinoic acid have continued to generate a large number of
      publications on this disease in the past 12 months, which concern both its
      biological and therapeutic aspects.

PMID- 8868094
TI  - Central nervous system leukemia.
AB  - The treatment of central nervous system (CNS) leukemia still poses a significant
      challenge to the clinical oncologist despite significant advances in therapeutic
      strategies that are directly targeted at the CNS. This article reviews the
      evolving definition of CNS leukemia, the current status of therapy for the
      prevention and treatment of overt CNS leukemia, pharmacological considerations in
      the treatment of CNS leukemia, and the longterm sequelae of CNS-directed therapy,
      focusing on articles that have been published in the past 2 years. New agents and
      treatment strategies for the treatment and prevention of CNS leukemia are also
      discussed.

PMID- 8868095
TI  - Biology and treatment of myeloma.
AB  - New strategies for the treatment of multiple myeloma, particularly high-dose
      therapy with peripheral blood stem cell transplantation, can achieve complete
      response in up to 50% of cases. The patient's condition eventually relapses
      because transplantation does not completely eliminate myeloma. Posttreatment
      interferon may prolong responses achieved by transplantation or chemotherapy, but
      it does not necessarily prolong survival. New approaches are being developed to
      further eliminate myeloma cells after an incomplete response achieved by
      transplantation or other chemotherapy. These approaches aim at myeloma cell
      surface antigens, T-cell immunity, and biological mechanisms of myeloma growth
      and dissemination. Biological targets include interleukin-6 (the central myeloma
      growth factor), interleukin-1 beta (an amplifier of stromal and bone cell
      production of interleukin-6), and serum soluble interleukin-6 receptor (an
      enhancer of myeloma cell response to interleukin-6). Efforts to eliminate
      circulating myeloma cells from peripheral blood stem cell harvests use positive
      selection or purging to provide a product that will engraft only normal stem
      cells, not myeloma cells. Multidrug resistance, a major factor in treatment
      failure, can be reversed by agents that inhibit the multidrug resistance protein
      on the myeloma cell surface. Finally, expanded knowledge of biologic mechanisms
      has led to the development of new prognostic factors. These aim to identify
      patients in clinical trials who can benefit from treatment regimens designed to
      overcome their impact on survival. Translating new biological advances into
      treatment programs is essential to improving therapy for patients with myeloma.

PMID- 8868096
TI  - Endocrine tumors.

PMID- 8868097
TI  - Diagnosis and management of adrenal tumors.
AB  - Tumors of the adrenal gland are not uncommon. Patients with these tumors usually
      demonstrate symptoms associated with the biochemical substance or hormone
      produced by the tumor. Tumors of the adrenal cortex, whether benign or malignant,
      are often associated with excess production of steroids, whereas tumors of the
      medulla are generally associated with overproduction of catecholamines. With the
      ubiquitous use of computed tomographic imaging, many asymptomatic adrenal lesions
      are discovered, presenting a management problem for the clinician. The algorithm
      for investigating so-called adrenal "incidentalomas" in the current era of cost
      containment continues to evolve. This review addresses current trends in the
      clinical evaluation, biochemical testing, and nuclear and radiologic imaging in
      the diagnostic work-up of these neoplasms. The mainstay of treatment is still
      surgical extirpation, the only curative modality. However, advances have occurred
      in adjuvant therapies, perhaps best typified by the neoadjuvant use of 131I
      methyl iodobenzylguanidine in the treatment of neuroblastoma.

PMID- 8868098
TI  - Advances in the diagnosis and management of well-differentiated thyroid cancers.
AB  - The well-differentiated thyroid carcinomas include papillary and follicular
      thyroid cancers. Approximately 14,000 new cases of thyroid carcinoma are
      diagnosed in the United States annually, but there are only 1100 deaths annually
      from thyroid malignancies. This relatively good prognosis is attributed to the
      biology of thyroid carcinoma and the current methods of treatment. Current
      investigations are aimed at expanding our understanding of thyroid carcinoma
      biology and optimizing treatment in a cost-effective manner.

PMID- 8868099
TI  - Advances in the use of somatostatins in the management of endocrine tumors.
AB  - With the introduction of long-acting somatostatin analogues, several advances
      have been made in the management of endocrine tumors. Octreotide was first used
      for the management of acromegaly and later used for metastatic
      gastroenteropancreatic tumors. Somatostatin receptor imaging has recently been
      introduced not only for the localization of somatostatin receptor-positive tumors
      but also for selection of optimal therapy. In addition to inhibitory effects on
      exocrine and endocrine secretion, octreotide has also been suggested to have
      antiproliferative effects manifested mainly by stabilization of disease and not
      tumor regression.

PMID- 8868100
TI  - The type II transforming growth factor-beta receptor as a tumor-suppressor gene.
AB  - Recent work has shown that: 1) loss of transforming growth factor-beta response
      is associated with malignant progression, 2) maintenance of autocrine negative
      transforming growth factor-beta activity is a key impediment to malignant
      progression, and 3) the major mechanism for loss of RII expression in replication
      error-positive colorectal cancer patients is mutation of the poly A tract of the
      transforming growth factor-beta receptor type II (RII) gene resulting in the
      generation of a premature STOP codon. Major issues for the role of RII in cancer
      are identified as the determination of the penetrance of mechanisms of RII loss
      in non-replication error tumors and other types of malignancies in addition to
      colon cancer. Analysis of mechanism of RII loss may prove to have clinical use in
      defining the clinical course of subset of different types of malignancies and, in
      addition, it may result in the identification of new therapeutic targets and
      approaches for some subsets of cancers.

PMID- 8868101
TI  - Oncogenic signaling.
AB  - Cancer develops when one or more cells begin to grow uncontrollably, presumably
      as a result of alterations in the highly regulated processes of normal cell
      division. These changes may result from germline or somatic mutations in genes
      that control normal cell proliferation, resulting in oncogenes. Oncogenes-
      originally defined as viral genes that transformed mammalian host cells--code for
      proteins with diverse functions. Antioncogenes, or tumor-suppressor genes, code
      for proteins acting as brakes in the cell cycle. Mutations in or deletions of
      these genes release the brakes. An overview of cellular signaling pathways, how
      they may be altered in cancers, and recently reported clinical implications of
      abnormal expression of some oncogenes and tumor-suppressor genes will be
      presented here.

PMID- 8868102
TI  - Mechanisms and therapeutic implications of angiogenesis.
AB  - Angiogenesis is a key step in tumor growth and metastasis. Many angiogenic
      factors have been described, including vascular endothelial growth factor, basic
      fibroblast growth factor, and thymidine phosphorylase. More recently, a number of
      naturally occurring inhibitors of angiogenesis, including thrombospondin and
      angiostatin, have also been identified. The control of angiogenesis by inhibitors
      regulated by suppressor oncogenes or produced by tumors has emerged as an
      important mechanism. The development of quantitative assessment of vascular
      density in primary human tumors has produced a new independent marker of
      prognosis and could be helpful in selecting patients for antiangiogenic therapy.
      A large number of antiangiogenic agents are in development, however, new ways to
      assess their antitumor effects will be necessary for the treatment of advanced
      cancer. Stabilization of disease may occur by inhibiting new vessel growth, and
      thus, evidence for a decrease in blood supply should be sought by positron
      emission tomography scanning, magnetic resonance imaging, or other methods.
      Markers of angiogenesis in urine or blood will prove to be helpful in the
      monitoring of treatments.

PMID- 8868103
TI  - Telomerase activity in human cancer.
AB  - The chromosome ends are specialized nucleoprotein structures called telomeres,
      which are essential for stable chromosome maintenance. In tumor-derived cell
      lines telomeres are maintained by the ribonucleoprotein enzyme telomerase.
      Telomerase activity is repressed in almost all normal human somatic cells. Due to
      the end replication problem, progressive telomere shortening occurs in normal
      somatic cells, leading to a limited replicative capacity and eventually resulting
      in cellular senescence. In the presence of viral oncogenes or some somatic
      mutations that block cellular senescence, cells continue to divide and telomere
      erosion continues. This continuing telomere erosion ultimately leads to the
      activation of telomerase, a necessary event for the sustained growth of most
      human tumors.

PMID- 8868104
TI  - Gene therapy strategies for novel cancer therapeutics.
AB  - The context of this review highlights current strategies being employed in gene
      therapy for neoplastic diseases. Three main approaches, mutation compensation,
      molecular chemotherapy, and genetic immunopotentiation, have been undertaken.
      Mutation compensation relies on strategies to ablate activated oncogenes or
      augment tumor-suppressor gene expression. Molecular chemotherapy uses delivery of
      a toxin gene to tumor cells for eradication. Genetic immunopotentiation augments
      the host immune response against tumor-associated antigens via delivery of immune
      stimulatory molecules or delivery of foreign genes. Rapid implementation of a
      variety of gene therapy strategies have been undertaken for human clinical
      trials.

PMID- 8868105
TI  - Leukemia.

PMID- 8868106
TI  - Endocrine tumors.

PMID- 8868107
TI  - Cancer biology.

PMID- 8868108
TI  - Immunohistochemical study of intrinsic innervation in the human pancreas.
AB  - Immunohistochemical identification of nerve structures in the human pancreas was
      achieved using immunohistochemical techniques. The antibodies used are specific
      for the myelin present in the periphery of ganglia and pregangliar nerve fibers,
      and for adrenergic neurotransmitters as well. In this study we observed the
      presence of numerous ganglia and nerve fibers in the periacinar tissue and near
      vascular structures. Adrenergic neurotransmitters were detected within pancreatic
      islets. These results would reveal that the exocrine pancreatic component is
      mainly innervated by parasympathetic ganglia and pregangliar fibers, as observed
      in the alimentary canal. Diversely, the endocrine component seems to be regulated
      by nonmyelinic orthosympathetic postgangliar fibers and parasympathetic fibers
      forming the perivascular plexus. The morphology and distribution of nerve
      structures in the pancreas recall those of the alimentary canal because these
      organs share the same embryogenetic derivation.

PMID- 8868109
TI  - Immunohistochemical analysis of extracellular matrix components and cytoskeletal
      products of bone marrow stromal cells.
AB  - We analysed the cytoskeletal proteins and extracellular matrix components of in
      vitro cultured BMSC both in resting state and after activation with IFN gamma and
      TNF alpha, using an immunoperoxidase procedure. BMSC expressed fibronectin, alpha
      actin, beta-tubulin, vimentin and vinculin while cytokeratinpan, GFAP,
      neurofilament, desmin and laminin were not expressed. This pattern of expression
      was not affected by addition of TNF alpha and IFN gamma, but differs from human
      tonsil stromal cells for laminin expression and alpha-actin localization.

PMID- 8868110
TI  - Differential expression of IL-1 and TNF receptors in inflammatory arthritis and
      osteoarthritis.
AB  - Pathological joint events in both inflammatory arthritis and degenerative
      arthritis are perpetuated by complex cytokine interactions. Two cytokines, IL-1
      and TNF alpha, appear to be the major culprits in the pathogenesis of synovitis
      and in cartilage damage in these joint diseases. To analyze the expression of IL
      1 and TNF alpha and their receptors on synovial and cartilage tissue, we
      performed an immunohistochemical study on knee biopsies from patients with
      rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA).
      Results identified a prevalent positivity to cytokines and their receptors of
      synovial cells from RA and PsA with respect to OA patients. In cartilage
      specimens, most RA and PsA patients showed no expression of the studied
      receptors, whereas the majority of OA biopsies were positive for all types of
      examined receptors except IL-1R2. Our study suggests that the cartilage is the
      main target of these cytokines in OA, while in IA IL-1 and TNF alpha exert their
      action in synovial tissue. In all the studied pathologies (RA, PsA, OA) the
      synovial tissue and the cartilage were differentially involved, indicating the
      importance of investigating both structures in joint disease studies.

PMID- 8868111
TI  - Lytic activity of IL-2 and IL-12 stimulated NK cells against HOS osteosarcoma
      cell line.
AB  - NK cells are CD16, CD56 positive lymphocytes that spontaneously lyse tumor or
      virus infected cells. In this study we investigated whether IL-2 and/or IL-12
      stimulated NK cells increased their lytic efficiency against HOS osteosarcoma
      cell line. Our results demonstrate that both 18 hour and 5 day incubation times
      enhanced the lytic activity of human PBL against HOS and K562 target cells and
      that IL-12 appears to be more efficient than IL-2 in augmenting NK cytotoxicity.

PMID- 8868112
TI  - Synthesis and biological evaluation of proline derivatives as potential
      angiotensin converting enzyme inhibitor.
AB  - The synthesis of a series of proline derivatives (1a-e and 2a-b) as pure isomers
      is described. These compounds were evaluated in vitro for their ability to
      inhibit angiotensin converting enzyme (ACE) and compared to the potency of
      captopril taken as a reference drug. They showed only a weak ACE inhibitory
      activity.

PMID- 8868113
TI  - Inhibition of galactonolactone dehydrogenase activity by lycorine.
AB  - Galactonolactone dehydrogenase, a mitochondrial enzyme catalyzing the last step
      in ascorbate biosynthesis, is strongly inhibited by lycorine. A concentration of
      10 microM of the alkaloid fully inhibits the activity of the enzyme. The high
      sensitivity of this enzyme to lycorine supports the hypothesis that the lycorine
      specifically inhibits ascorbate biosynthesis and that all the other metabolic
      responses to lycorine treatment depend on this primary inhibition of ascorbate
      biosynthesis.

PMID- 8868114
TI  - Dynamic internal coordination in different frequency ranges.

PMID- 8868115
TI  - Adrenal catecholamines after chronic erythropoietic stimulus.

PMID- 8868116
TI  - Lack of antibodies to the envelope glycoproteins of hepatitis C virus in
      immunoglobulin preparations from screened donors.

PMID- 8868117
TI  - [Aging and mental disorders].

PMID- 8868118
TI  - [Female Medicine in the Elderly].

PMID- 8868119
TI  - [Sedation with flunitarazepam at magnetic resonance imaging in the elderly
      patients with dementia].
AB  - Magnetic resonance imaging (MRI) of the brain is useful in diagnosing senile
      dementia, but to avoid the creation of artifacts the patient should be kept
      immobile. We studied the effects of pretreatment with flunitrazepam, a sleep
      inducer of the benzodiazepine class, as a sedative prior to imaging. The subjects
      consisted of 108 patients with senile dementia admitted to the Dementia Ward of
      Kyoto Higashiyama Geriatric Hospital. Their ages ranged from 64-95 years (mean,
      81) and the mean body weights of the 76 women and 32 men were 36 and 47 kg,
      respectively. Immediately before undergoing MRI the patients were given a slow
      intravenous injection of flunitrazepam (2 mg/ml diluted in 19 ml of saline).
      Immediately before the patients fell asleep, administration was discontinued and
      the dose was noted: mean 0.008 mg/kg. In all patients sleep induction and
      sedation were achieved. No adverse reactions such as apnea were observed. The
      flunitrazepam dose in our study was much lower than that in previous reports on
      adults. As body weights of the elderly are also lower than those of younger
      adults, the optimum dose of flunitrazepam for the elderly may be much lower.
      Intravenous flunitrazepam may be a useful and safe premedication for MRI in
      elderly patients with dementia. To avoid serious adverse reactions the dose
      should be minimized by: 1) determining body weight before MRI, 2) administering
      diluted flunitrazepam, and 3) discontinuing the drug before the patient falls
      asleep.

PMID- 8868120
TI  - [Circumstances and factors related to falls in the institutionalized elderly].
AB  - The circumstances and factors related to falls among the elderly living in a
      nursing home were investigated. Information on falls was obtained from the fall
      assessment form recorded by the staff of the institution. During the 1-year study
      period, 65 (37%) of 174 subjects experienced at least one fall. Most falls
      occured in the subjects' own rooms and during the daytime. In the subsample of 52
      elderly whose data on age, sex, gait, grip strength and standing on one leg at
      tha beginning of this study were available, week grip strength was significantly
      associated with increasing risk of falling by chi-square test. After adjusting
      for other factors, weak grip strength remained a significant and independent
      predictor of falls. Measuring of grip strength may be useful for screening
      elderly who are at a high risk of falling.

PMID- 8868121
TI  - [Infection in elderly leukemic patients].
AB  - Febrile episodes occurring in 29 elderly patients (mean age 75 years) with
      leukemia, from 1988 to 1993, were reviewed. A febrile episode was defined as a
      temperature of 38 degrees C or greater for at least 6 hours. The number of
      febrile episodes was 64. The average was 2.2 febrile episodes per patient.
      Seventy-two percent of febrile episodes occurred when the patients had
      neutropenia below 100/microliters, while 16% occurred with neutropenia of
      101/microliters to 500/microliters. Causative microorganisms were identified in
      48% of total febrile episodes. The most common infectious site was the urinary
      tract which accounted for 25% of total episodes. Pneumonia and septicemia
      accounted for 22% of total episodes, respectively. Gram-positive cocci were
      responsible for 66% of microbiologically documented febrile episodes, while 21%
      were caused by gram-negative bacilli. Gram-positive cocci, particularly
      staphylococcus aureus, coagulae-negative staphylococcus and enterococci increased
      compared with a decade ago in our department. Granulocyte colony-stimulating
      factor (G-CSF) was used 12 times for infection. No significant difference in
      fever amelioration was seen between G-CSF and non-G-CFS cases.

PMID- 8868122
TI  - [Influence of social environments on brain aging].
AB  - To investigate influence of social activity on normal brain aging, we studied the
      social activity score, cognitive functions, self-rating depression scale,
      cerebral blood flow (CBF), MRI and motor function in the normal elderly people
      living in different social environments. There was no difference in risk factors
      for stroke, MRI findings and CBF between the two groups. However, the subjects
      living in a home for elderly showed significantly lower social activities than
      those living with families. Cognitive functions and motor function were lower,
      and SDS was higher in subjects living in retirement house than those living with
      families. The social environment including social activities closely related to
      life style may significantly influence brain aging with regard to silent brain
      infarctions or risk factors for stroke.

PMID- 8868123
TI  - [The effect of ACE inhibitors, beta blockers and calcium antagonists on the
      responses to pressor stress tests in the elderly hypertensive patients].
AB  - The purpose of the study was to elucidate the effects of antihypertensive drugs
      on the hemodynamics in elderly hypertensive patients. Forty-two elderly
      hypertensives (mean 72 +/- 5 years) were given either ACE inhibitors (A group:
      perindopril in 10 and captopril in 4 cases), beta blockers (B group: arotinolol
      in 15 cases) or calcium antagonists (C group: nifedipine in 3 and nitrendipine in
      10 cases) for 8-12 weeks. The responses to handgrip and mental arithmetic stress
      and cardiac functional changes were determined by echocardiography before and
      after the medications. The decrease in blood pressure at rest and on the stress
      tests was similar among the three groups, though the hemodynamic responses to the
      stress tests showed some differences. In the A group, no hemodynamic changes were
      seen either at rest or on the stress tests after the medication. In the B group,
      the heart rate and the cardiac output were decreased at rest, and the increase of
      them on the stress tests were diminished after the medication. On the contrary,
      the heart rate and the cardiac output were increased, and showed exaggerated
      responses on the stress tests in the C group. In conclusion, in antihypertensive
      treatment of elderly hypertensive patients it is important to consider the
      effects of the antihypertensive drugs on the hemodynamics, although the
      comparable decrease in blood pressure is expected.

PMID- 8868124
TI  - [Two cases of Candida endocarditis associated with abdominal disease].
AB  - Two cases of Candida endocarditis are reported. The first case was of a 63-year
      old man who had a positive blood culture for Candida albicans during treatment
      for liver abscess and early gastric cancer. He was transferred to our department,
      and aortic and tricuspid regurgitation due to Candida endocarditis was diagnosed.
      The patient was successfully treated with aortic valve replacement, tricuspid
      valve plasty and anti-fungal agents. The second case was of a 65-year-old man who
      complained of fever. Despite a diagnosis of common bile duct cancer and resection
      of the tumor, the fever persisted. He was transferred to our department and was
      diagnosed having aortic regurgitation due to Candida endocarditis, complicated by
      heart failure. Although intense medical therapy including antifungal agents,
      diuretics, catecholamines and digoxin was initiated, the patient died from
      multiple embolisms 9 days later. In the treatment of Candida endocarditis, early
      diagnosis and early decision-making for either surgical or medical therapy is
      indispensable. Although the prevalence of Candida endocarditis is low, the
      differentiation of this disease should be taken into account in febrile elderly
      patients with long-standing therapy with antibiotics.

PMID- 8868125
TI  - [An elderly patient with Leriche syndrome complicated by congestive heart failure
      and rhabdomyolysis].
AB  - A 64-year-old man, who had had bilateral intermittent claudication and leg pain
      for five years, was admitted because of sudden onset of severe leg pain, and
      acute respiratory failure. Laboratory data showed markedly elevated serum CK of
      73,050 IU/L, and urinary myoglobin of 430,000 ng/ml. A diagnosis of
      rhabdomyolysis was made. Renal dialysis was required for the next two days
      because of acute renal failure. The aortogram was performed on the 32nd day and
      disclosed complete obstruction of the abdominal aorta immediately distal to the
      bilateral renal arteries. Good collateral flow was noted to the popliteal
      arteries. On the 49th day, the patient successfully underwent extra-anatomical
      bypass surgery (axillo-bifemoral bypass). The mechanism of rhabdomyolysis in this
      elderly patient was discussed.

PMID- 8868126
TI  - [Case of a hypertensive centenarian who was able to record 24-hr ambulatory blood
      pressure].
AB  - Our visiting health-check team has followed a 102 year-old centenarian male for 2
      years. During this period his blood pressure (BP) was always normal and
      physically he was almost always in good condition. Physical examinations and
      blood tests revealed no remarkably abnormal findings. In March, a household BP
      measuring instrument indicated a rise in systolic BP to more than 190 mmHg.
      Consequently, his family physician administered a calcium channel blocking anti
      hypertensive agent (Nifedipine: Adalat L; 20 mg/day). However, after taking the
      medicine he felt sick and stopped taking it. During our visit in June, his family
      requested us to carry out further examination, while continuing to record his BP.
      His physical and hematological data showed no abnormal findings. We tried to
      record his normal ambulatory BP during an entire day, first, without drugs, and
      then followed by medication (Nifedipine 10 mg/day). The results revealed a great
      gap of pre- and post-medication BP with a maximum of 100 mmHg during the day. We
      should therefore be much more careful in administering and hypertensive agents
      such as calcium channel blockers to the very elderly.

PMID- 8868127
TI  - Metabolism of psychotropic drugs: pharmacological and clinical relevance.
AB  - Cytochrome P-450 (CYP) catalyzes phase I metabolic reactions of psychotropic
      drugs. The main isoenzymes responsible for their biotransformation are CYP1A2,
      CYP2D6, CYP3A4 and these of the subfamily CYP2C. The majority of metabolites of
      psychotropic drugs are biologically active. Some of them retain pharmacological
      properties of parent compounds (eg. selective serotonin reuptake inhibitors,
      risperidone, carbamazepine, benzodiazepines), but others display quite different
      (eg. amitriptyline, buspirone) or even opposite (trazodone) profiles. They are
      present in vivo in concentrations high enough to contribute to pharmacological
      and clinical effects of the administrated drugs. Active metabolites of
      psychotropics are also characterized by pharmacokinetic properties different from
      their parent compounds, e.g. half-life time, plasma protein binding, blood-brain
      barrier penetration, the cerebrospinal fluid (CSF) protein binding and tissue
      binding. These properties lead, in turn, to differences in the brain/plasma and
      the CSF/plasma concentration ratios between a drug and its metabolites. Therefore
      studies relating a pharmacological or therapeutic response of psychotropic drug
      to its plasma concentrations should not disregard the presence of its active
      metabolites, considering their distinct pharmacological and pharmacokinetic
      properties. With regard to a low therapeutic index of psychotropics,
      interindividual differences in the rate of their metabolism, genetic polymorphism
      of their main metabolic pathways and metabolic interactions in clinical drug
      combinations, the phenotyping of patients at the beginning of therapy and a
      control of drug concentrations (and its active metabolites) at a steady state and
      during coadministration of another drug, may increase the efficiency and safety
      of the pharmacotherapy of psychiatric disorders.

PMID- 8868128
TI  - Influence of serotonergic drugs on restraint stress induced analgesia.
AB  - The effects of drugs selectively effecting central serotonergic systems on
      immobilization-induced analgesia (SIA) were tested in the rat. The drugs were
      used in dose ranges previously shown to effect emotional processes. SIA was
      tested using the tail withdrawal method. It was found that pretreatment of rats
      with para-chlorophenylalanine (p-CPA), an inhibitor of serotonin synthesis,
      significantly attenuated SIA, measured immediately after stress session.
      Ritanserin, a 5-HT2A/2C receptor antagonist, ondansetron, a 5-HT3 receptor
      antagonist and citalopram, a selective serotonin re-uptake blocker increased the
      baseline pain threshold, whereas 8-OH-DPAT, a full 5-HT1A receptor agonist and
      buspirone, a partial 5-HT1A receptor agonist expressing also high affinity
      towards dopaminergic D2 receptors, were without effect on pain perception and
      stress induced analgesia. It has been concluded, that modification of SIA by
      serotonergic drugs probably merely reflects changes in the activity of the 5-HT
      system on the spinal cord level, with minor, if any, contribution of supraspinal
      emotional centers.

PMID- 8868129
TI  - Locomotor activity pattern induced by diazepam in control and caffeine-treated
      mice.
AB  - The effect of diazepam on locomotor activity was tested by measuring the number
      of crossings between two compartments of a toggle-floor box, in control mice
      (water drinking) and in mice receiving caffeine solution (0.5 g/I) instead of
      drinking water. In control mice, diazepam did not produce any significant change
      in total activity measured on the whole 60-min test, but animals showed phases of
      increased activity broken by periods of immobility. After chronic ingestion (18
      days) of caffeine, doses of 0.5, 1 and 2 mg/kg ip diazepam significantly
      increased total locomotor activity. Caffeine slightly reduced diazepam-induced
      immobility and increased the frequency of crossings in active periods. Taken
      together, these two effects may explain the significant increase in total
      activity induced by diazepam in caffeine-treated mice. Mixed stimulatory
      depressant action was also produced by 3 mg/kg diazepam, a dose that slightly
      decreased the total activity.

PMID- 8868130
TI  - Effects of aflatoxin B1 on the sensitivity of the rat central nervous system to
      pentobarbital-Na racemate.
AB  - The immobility time of pentobarbital was prolonged in male rats treated with
      aflatoxin B1 (AFB1), 2 mg/kg, with maximum on the 3rd day after treatment. It
      cannot be fully explained by the pharmacokinetic mechanisms. In parallel ED50 of
      pentobarbital was decreased both in males and females. In males the lethal dose
      of pentobarbital was decreased by about 30%. The pentobarbital concentration in
      the brain was increased during the immobility time and at awakening after the ip
      administration of 40 mg/kg of the drug on the 3rd day after AFB1 treatment with
      doses of 1 mg/kg and 2 mg/kg po in males and females, respectively. The plasma
      concentration of pentobarbital was significantly increased in treated males only.
      The content of unchanged pentobarbital in urine within 24 h after its
      administration was not high (about 1% in males, 2% in females) and in the AFB1
      treated animals it virtually did not change. The elevation of the brain level of
      barbiturate at the time of awakening in AFB1 treated animals may point to a
      decreased sensitivity to pentobarbital.

PMID- 8868131
TI  - Repeated amphetamine administration down-regulates glucocorticoid, but not
      mineralocorticoid, receptors in the rat hippocampus.
AB  - It has been postulated that activation of the hypothalamic-pituitary-adrenal
      (HPA) axis is critical to the development of sensitization to amphetamine. Since
      this axis is under inhibitory control of hippocampal corticosteroid receptors,
      the present study has been designed to determine the effects of repeated (5
      mg/kg, ip, twice a day for 14 days) d-amphetamine (AMPH) administration on
      binding parameters of these receptors. Glucocorticoid (GR) and mineralocorticoid
      (MR) receptors were examined by an in vitro [3H]corticosterone binding in the
      cytosol from the rat hippocampus, using the selective GR agonist RU 28362 to
      discriminate between MR and GR. Repeated, but not single, treatment with AMPH
      significantly reduced the density of GR (decrease by ca. 20%). The density of MR
      tended to decrease 2 h, but not 72 h, after the last drug injection. No changes
      in dissociation constants were found following single or repeated AMPH
      administration. The plasma corticosterone level was significantly increased 1, 2
      and 72 h after chronic administration of AMPH. Obtained results indicate that
      repeated AMPH administration down-regulates GR receptors and increases plasma
      corticosterone level. These changes may reflect neurochemical mechanism of
      addictive properties of AMPH.

PMID- 8868132
TI  - Influence of selected antiarrhythmic drugs on the hemodynamic parameters in
      rabbits during anesthesia. Part III. Ketamine anesthesia.
AB  - The influence of procainamide, N-acetylprocainamide, verapamil or propranolol on
      hemodynamic parameters in rabbits was studied during ketamine anesthesia. Using
      radioisotopic methods the following parameters were estimated: cardiac output,
      stroke volume, total peripheral resistance, renal and hepatic blood flows,
      arterial pressure and heart rate. During ketamine anesthesia the inhibitory
      effect of verapamil on peripheral resistance was intensified; after
      administration of the rest of antiarrhythmic drugs the decrease of peripheral
      resistance was not observed in the animals without general anesthesia. During
      ketamine anesthesia the negative chronotropic effect of N-acetylprocainamide was
      decreased, but the negative chronotropic effect of procainamide was intensified.
      Procainamide administration during ketamine anesthesia markedly decreased renal
      blood flow. Propranolol given without anesthetic, as well as given together with
      ketamine markedly decreased hepatic blood flow.

PMID- 8868133
TI  - Influence of captopril on the serotonin-induced vasopressor effect in tail artery
      isolated from two-kidney, one-clip renal hypertensive rats.
AB  - The influence of captopril and ritanserin (5-HT2 receptor antagonist) on the
      serotonin-induced contraction of isolated tail artery of two-kidney, one clip
      hypertensive (2K, 1C-RHR) and normotensive rats was studied. Captopril,
      administrated in a single dose of 100 mg/kg, po or in a dose of 30 mg/kg/day, po
      for one week, diminished the systolic blood pressure in both groups of rats.
      Ritanserin (0.01 mg/kg/day, sc for one week) administrated alone or in
      combination with captopril (30 mg/kg/day) evoked such effect only in 2K, 1C-RHR.
      The reactivity of rat tail artery isolated from 2K, 1C-RHR to serotonin was
      significantly higher than that obtained from normotensive ones. Captopril given
      in a single dose or chronically did not change the serotonin-induced contraction
      of rat tail artery in normotensive rats. The attenuation of serotonin contractile
      effect was registered in hypertensive rats pre-treated with captopril.
      Administration ritanserin with or without captopril also inhibited the response
      to serotonin in both groups. The stronger effect was observed after
      administration of ritanserin with captopril in 2K, 1C-RHR than in control group.
      Our results indicate, that in 2K, 1C-RHR the reactivity of rat tail arteries to
      serotonin is enhanced and this effect can be reduced by chronic captopril
      administration.

PMID- 8868135
TI  - Analysis of diltiazem and desacetyldiltiazem in serum by high-performance liquid
      chromatography.
AB  - This paper describes a simple high-performance liquid chromatographic (HPLC)
      method for the determination of diltiazem and desacetyldiltiazem in human serum.
      After basic methyl-tert-butyl ether extraction and back-extraction with
      hydrochloric acid, the drug and its metabolite was injected into a Supelcosil LC
      CN column and the absorbance of the eluate was measured at 240 nm. The
      sensitivity was 5 ng/ml and the obtained precision, selectivity and stability
      during storage were adequate for the performed clinical studies in patients
      therapeutically treated with diltiazem.

PMID- 8868134
TI  - Effects of thiorphan, bestatin and captopril on the Lewis lung carcinoma
      metastases in mice.
AB  - Previously we have found that administration of thiorphan alone or in combination
      with bestatin exerts antitumor effect in mice, including reduction of B16
      melanoma tumor growth and prolongation of survival time. These data prompted us
      to extend our studies to estimate the effect of treatment with thiorphan,
      captopril and bestatin on lung metastases in mice. Administration of thiorphan
      alone at a dose of 25 micrograms/mouse or in combination with bestatin (50
      micrograms) or captopril (5 mg/mouse) decreased the number of spontaneous
      metastases in lungs of Lewis lung carcinoma bearing mice. Neither the injections
      of bestatin, captopril nor bestatin in combination with captopril influenced the
      number of lung tumor colonies. Treatment with thiorphan at a dose 25 micrograms
      augmented cytotoxic activity of natural killer (NK) cells and macrophages. These
      observations explain partly the mechanism of action of thiorphan.

PMID- 8868136
TI  - Synthesis and pharmacological properties of 2,4-disubstituted 5-amino-6
      pyrimidinecarboxylic acid derivatives. Part III.
AB  - 2,4-Disubstituted 5-amino-6-pyrimidinecarboxylic acid derivatives 5-13 were
      synthesized and evaluated for their pharmacological activity. Compounds 5, 7, 9,
      10 and 12 showed antiaggressive effect, compounds 6 and 10 showed synergism with
      hexobarbital while compound 6 exerted analgesic activity.

PMID- 8868137
TI  - Effects of heroin on thyroid function, cortisol and testosterone level in
      addicts.
AB  - Studies were carried out on 50 heroin addicts receiving heroin. Serum
      concentration of triiodothyronine (T3), thyroxine (T4), thyroid stimulating
      hormone (TSH)--to test thyroid function--as well as cortisol and testosterone
      were measured and compared with values of 25 normal males. Urine samples of
      addicts were tested for the presence of morphine. Heroin does not affect the
      serum level of T4 and TSH but a slight increase in triiodothyronine was observed.
      Heroin was found to exert a lowering/depleting effect on serum cortisol and
      testosterone level in more or less all the addicts irrespective of age, dose of
      heroin per day and period of drug intake.

PMID- 8868138
TI  - Effects of a new oxazolidinone derivative AS-8 on serotonin metabolism in the
      brains of mouse, rat and chick.
AB  - The effect of 5-morpholinemethyl-3-(4-chlorobenzylideneamino)-2-oxazolidin one
      (AS-8), a potential antidepressant drug, was tested on 5-hydroxytryptamine (5-HT)
      metabolism in the brains of rat, mouse and chick. The ip administration of AS-8
      (25-500 mg/kg) did not modify the cerebral 5-HT level, but significantly
      increased the level of 5-hydroxyindoleacetic acid (5-HIAA) the main 5-HT
      metabolite. In animals receiving pargyline (a MAO-A inhibitor which blocks 5-HT
      catabolism), AS-8 markedly enhanced 5-HT accumulation in the brains of rats and
      mice, but not chicks. It is concluded that AS-8 is capable of stimulating of 5-HT
      synthesis at least in the mammalian brain.

PMID- 8868139
TI  - Immunomodulatory activity of disulphide bridged peptides related to lactoferrin
      immunosuppressive mini-domain.
AB  - The following peptides, related to the immunosuppressive loop of lactoferrin (I)
      and containing the sequence Arg-Lys-Pro-Val-Asp (II) were synthesized [sequence:
      see text] and their influence on humoral and cellular immune response was
      evaluated. It was found that all these peptides lack the immunosuppressive
      activity regarding the humoral immune response, but show quite strong
      immunosuppressive activity with respect to the cellular immune response. It may
      suggest, that the peptide conformational requirements for the suppression of the
      cellular and humoral immune response are different.

PMID- 8868140
TI  - Cardiopharmacological profile of HOE 234, the new activator of ATP-sensitive K+
      channels in the guinea pig heart.
AB  - The direct chronotropic and inotropic effects of HOE 234, the new activator of
      ATP sensitive K+ channels (KATP) were examined in isolated preparations of right
      ventricle papillary muscle and right atria from the guinea pig heart. HOE 234
      (0.3-3 microM) produced concentration-dependent negative inotropic (IC50 = 0.5 +/
      0.1 microM) and chronotropic (IC50 = 0.56 +/- 0.08 microM) effects. These
      effects were significantly attenuated by glibenclamide, a selective blocker of
      KATP channels in the heart muscle, with pA2 = 6.6 for inotropic and 6.65 for
      chronotropic action of HOE 234. The results have shown that HOE 234 activates the
      KATP in the guinea pig papillary muscle as well as in the right atria with a high
      affinity. The onset of the negative inotropic and chronotropic effects was fast
      and similar in both preparations (5-7 min). However, the time needed for the
      recovery of the force of contraction was markedly longer (about 90 min) than that
      for the right atria to return to the control rate (about 40 min). The effects of
      HOE 234 compared to those of other known activators of KATP suggest its higher
      selectivity to myocardium.

PMID- 8868141
TI  - Inhibitory effect of neuropeptide y on epileptiform activity in the frontal
      cortex and hippocampus in vitro.
AB  - The effect of neuropeptide Y on spontaneous epileptiform discharges was studied
      in cortical and hippocampal slices using an extracellular recording. Epileptiform
      activity which was induced by superfusion of slices with Mg(2+)-free medium was
      attenuated by neuropeptide Y (0.5 microM) in both the frontal cortex and
      hippocampal CA1 pyramidal cells.

PMID- 8868142
TI  - Endothelial nitric oxide, prostacyclin (PGI2) and tissue plasminogen activator (t
      PA): alliance or neutrality?
AB  - In vivo a powerful triad of endothelial secretogogues regulates thrombo
      resistance and vascular tone. In physio-pathological circumstances stimulation of
      endothelial receptors (purinergic, muscarinic, kinin) releases prostacyclin
      (PGI2), nitric oxide (NO) and tissue plasminogen activator (t-PA) in a coupled
      manner. Alliance between them occurs at level of protection against deposition of
      thrombi over the vascular wall. Activation of fibrinolysis by t-PA through
      generation of plasmin is complemented with multifactorial desactivation of
      platelets by PGI2 and a selective inhibition of release of plasminogen activator
      inhibitor-1 (PAI-1) from platelets by NO. This concerted action of the triad
      leads to increase in anti-thrombotic and thrombolytic potentials. Administrated
      separately t-PA (or streptokinase) and PGI2 (or iloprost) produce unwanted
      effects such as "paradoxic thrombogenesis" or "rebound activation of platelets",
      respectively. It is because they are missing a natural ally. On the other hand,
      endothelial regulation of vascular tone depends on NO, exclusively. Only
      exogenous PGI2 is hypotensive, and even then it does not synergize with NO. In
      vitro all types of interactions between PGI2 and NO occur. For instance,
      synergism--in platelets, addition--in vascular smooth muscle and antagonism--in
      macrophages. Activity of arachidonate cyclooxygenase is claimed to be either
      stimulated or inhibited by NO. A transfer of conclusions from in vitro data to
      living systems must be very cautious.

PMID- 8868143
TI  - Inhibition of nitric oxide synthesis improves arterial oxygenation in
      ethchlorvynol-induced acute lung injury in dogs.
AB  - In both humans and in experimental animals, acute lung injury (ALI) is
      characterized by the development of pulmonary edema and arterial hypoxemia. It
      has been reported that the hypoxemia of ALI is related to the failure of those
      mechanisms that result in the diversion of blood flow away from hypoxic
      (edematous) lung units to those that are well oxygenated. One such mechanism is
      hypoxic pulmonary vasoconstriction (HPV). In the pulmonary circulation,
      endogenous nitric oxide (NO) has been shown to oppose HPV and, thereby, to
      support blood flow to hypoxic alveoli. In the present work we investigated the
      hypothesis that, in ALI, endogenous NO, by virtue of its ability to oppose HPV,
      supports blood flow to hypoxic lung units resulting in increases in venous
      admixture (Qva/Qt) and decreases in arterial oxygen tension (PaO2). In
      anesthetized and mechanically ventilated dogs, the intravenous administration of
      ethchlorvynol (ECV, 15 mg/kg) resulted in an increase in extravascular lung water
      (EVLW) of 10 +/- 1 ml/kg body wt (p < 0.001) as well as a 120 +/- 45% increase in
      Qva/Qt (p < 0.01) and a 23 +/- 5% decrease in PaO2 (p < 0.01) (n = 3). L-NAME (1
      mg/kg iv, followed by 5 mg/kg/h, iv), administrated 60 min after ethchlorvynol
      (ECV), prevented entirely the ECV-induced increase in Qva/Qt and fall in PaO2
      with minimal effect on EVLW (n = 3). We conclude that, in this model of ALI,
      endogenous NO is present in the lung and acts to support blood flow to poorly
      oxygenated lung units resulting, thereby, in reductions in PaO2.

PMID- 8868144
TI  - Myocardial reactive hyperaemia in perfused guinea pig heart.
AB  - Reactive hyperaemia (RH) was induced by occlusion of coronary flow (1-60 s) in
      perfused guinea pig heart. It was inhibited by 100-60%, by NG-nitro-L-arginine
      (100 microM) and to a lesser extent (up to 35%) by 8-phenyltheophylline (10
      microM). Indomethacin (5 microM), did not affect RH. During RH the heart
      generated prostacyclin, nitric oxide and adenosine as indicated by the appearance
      of 6-keto-PGF1 alpha, cyclic GMP, inosine, hypoxanthine, xanthine and urate in
      the perfusate. Only nitric oxide (NO) and adenosine but not prostacyclin were
      responsible for RH. NO mediated RH which followed short-term (1-10 s) coronary
      occlusion whereas a combined effort of NO and adenosine was required to maintain
      RH that followed longer (20-60 s) periods of interruption of coronary inflow.
      Prostacyclin did not participate in RH at any circumstances.

PMID- 8868145
TI  - [Fibromyalgia--an artifact?].

PMID- 8868146
TI  - [New aspects in the pathogenesis of Bechterew disease].
AB  - The association of HLA-B27 with ankylosing spondylitis (AS), first described more
      than 20 years ago, triggered intensive research all over the world. AS is a
      disease model to study the interplay between genetic, immunologic, and
      environmental factors in the induction of rheumatic disease. Over the past years,
      substantial advances have taken place in the area of the molecular and cellular
      immunology of the HLA-B27 molecule, HLA-B27 subtype polymorphism, peptide binding
      and presentation to cytotoxic T cells, and their relevance to disease. New
      insights into the pathogenesis of the spondylarthropathies come from the
      development of animal models, namely HLA-B27/human beta 2-microglobulin
      transgenic rats, and HLA-B27 transgenic, beta 2-microglobulin knock-out mice. The
      role of gram-negative bacteria and gut inflammation in the development of
      ankylosing spondylitis continues to be the focus of interest in many studies. In
      this review, recent hypotheses of the pathogenesis of AS and its relationship to
      HLA-B27 are discussed.

PMID- 8868147
TI  - [Fibromyalgia and Sjogren syndrome--clinical and methodological aspects].
AB  - The prevalence of fibromyalgia in primary (n = 18) or secondary (n = 20)
      Sjogren's syndrome was examined. In all patients with Sjogren's syndrome as well
      as in 31 fibromyalgia patients and 20 healthy individuals measurements of
      pressure pain threshold were done by palpation and dolorimetry. Widespread pain,
      functional complaints, as well as depression were determined by a questionnaire.
      The results show a high frequency of fibromyalgia in the group of patients with
      pSS (44%), 72% of pSS patients reported widespread pain. Only 5% of the sSS
      patients fulfilled the ACR criteria for fibromyalgia and 40% of this group
      reported on widespread pain. Dolorimetry measures at tender or control points
      revealed that the pressure pain threshold was significantly reduced in all
      patient groups with healthy controls. There were only small differences between
      the clinical groups. Within the different groups examined there was a close
      correlation between dolorimetric threshold at tender and control points. In
      contrast to self-estimated widespread pain the pressure pain threshold was not
      closely related to functional complaints in the patient groups. The prevalence of
      depression was increased in both pSS and FM patients, in contrast to the other
      groups. The results suggest to include Sjogren's syndrome into the differential
      diagnosis of FM. The dolorimetric results were interpreted as an argument against
      the actual tenderpoint concept. They support the view that patients with FM
      rather represent an arbitrary coincidence of widespread pain and elevated
      tenderness on pressure.

PMID- 8868148
TI  - Psychotherapy in rheumatoid arthritis--a parallel-process study of psychic state
      and course of rheumatic disease.
AB  - In this study, well-known psychosomatic (psychoneuroimmunological) connections
      have been used for therapeutic purposes. Fifteen patients with rheumatoid
      arthritis (RA) were treated with analytical insight therapy for 60-90 min weekly
      during 10 months to 4.5 years (median 3.3 years). Six patients showed great and
      largely continuous improvement, both psychic and physical, throughout the period
      of psychotherapy and often for a long time thereafter. In another five cases,
      improvements in psychic state and the joint disease took place over a period of 1
      2 years. Later, when the emotional channels to childhood traumata were opened,
      these five patients relapsed and the course of their disease became more
      variable. In four cases, the connections between psychic state and the course of
      the joint disease were more varied throughout the period of psychotherapy. In the
      studied group the correlation between psychic state and course of rheumatic
      disease was highly significant. The probability of the outcome of the study being
      due to chance alone is considered very small, especially taking into account the
      fact that RA is a chronic progressive disease.

PMID- 8868149
TI  - [Evaluation of a German version of WOMAC (Western Ontario and McMaster
      Universities) Arthrosis Index].
AB  - The WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index is a
      tested questionnaire to assess symptoms and physical functional disability. We
      adapted the WOMAC for the German language and tested its metric properties, test
      retest reliability and validity in 51 patients with knee and hip OA. All WOMAC
      scales (pain, stiffness, function) were internally consistent with Cronbach's
      coefficient alpha ranging from 0.80 to 0.96. Test-retest reliability was
      satisfactory with intraclass correlation coefficients ranging from 0.55 to 0.74.
      All scales and the global index calculated as the mean of scale scores had a
      bimodal distribution and a slight ceiling effect. As hypothesized the WOMAC
      scales were associated with radiological OA-severity and limitations of range-of
      motion. Patients with more severe symptoms and functional disability perceived
      more limitations in their roles at home and at work. The presented German version
      of the WOMAC is a reliable and valid instrument for the assessment of symptoms
      and physical functional disability in patients with knee and hip OA.

PMID- 8868150
TI  - [Evaluation of a German questionnaire version of the Lequesne cox- and
      gonarthrosis indices].
AB  - The Lequesne algofunctional indices for the knee and the hip require a physician
      interview. We adapted the Lequesne indices for the German language and tested the
      metric properties, test-retest reliability and validity of a self-report
      questionnaire-format in 51 patients with hip or knee OA. The symptom and function
      components as well as the global indices had a high test-retest reliability
      (intraclass correlation coefficient knee: 0.87/0.92 and 0.86, hip: 0.96/0.85 and
      0.94). The symptom component showed an insufficient internal consistency
      (Cronbach's coefficient alpha knee: 0.55; hip: 0.63). Also, the symptom component
      was not or only weakly associated with radiological OA-severity and the
      limitations of range-of-motion. The most likely explanation is the grading of the
      Lequesne symptom questions which addresses such different concepts as pain
      presence, pain on movement, duration of pain and appearance of pain after a
      certain period of time. Because of the insufficient internal consistency and
      questionable validity the tested self-report German-version of the Lequesne
      algofunctional indices may not be recommended for use in clinical research and
      practice.

PMID- 8868151
TI  - [Livedo racemosa generalisata in atrial myxoma].
AB  - We describe a patient with livedo racemosa generalisata (LRG), Raynaud's
      phenomenon, multifocal recurring transitory and complete ischemic attacks and
      laboratory findings of systemic inflammation. Working diagnoses were vasculitis,
      mixed connective tissue disease, or Sneddon's syndrome, but echocardiography
      revealed a left atrial myxoma. Special staining of skin biopsies with alcian-blue
      showed arterial occlusion caused by myxomatous material. Arterial embolism by
      parts of the myxoma is suggested to be the cause of the LRG and probably the
      neurological findings.

PMID- 8868152
TI  - [Serotonin antibodies in fibromyalgia syndrome--expression of a
      neuroendocrinologic autoimmune disease?].

PMID- 8868153
TI  - [Comment on "Current aspects of SAPHO syndrome" by H. Kaiser].

PMID- 8868154
TI  - [Comment on H. Kaiser: "Current aspects of SAPHO syndrome"].

PMID- 8868155
TI  - [Comment on H. Kaiser: "Current aspects of SAPHO syndrome"].

PMID- 8868156
TI  - Tori mandibularis.

PMID- 8868157
TI  - Awareness of oral cancer.

PMID- 8868158
TI  - Recognition of medically necessary oral health care.

PMID- 8868159
TI  - Recognition of medically necessary oral health care.

PMID- 8868160
TI  - Nutrition: what priority do you give it?

PMID- 8868161
TI  - Good news on amalgam.

PMID- 8868162
TI  - A prescription for the future of dental benefits in Canada.

PMID- 8868163
TI  - Protection and prevention: a two-way approach to office insurance.

PMID- 8868164
TI  - "2,000 patients"--what do you mean?

PMID- 8868165
TI  - Team meetings ... again.

PMID- 8868166
TI  - The power of your vocal image.
AB  - Your vocal image is the impression that listeners form of you based on the sound
      of your voice. In a dental office, where the initial patient contact usually
      occurs over the phone, your vocal image is vitally important. According to social
      psychologists, people begin to make relatively durable first impressions within
      six to 12 seconds of perceiving a sensory cue. This means that patients begin to
      form their impressions of a telephone speaker almost immediately. Based on the
      qualities of the speaker's voice and how it is used, they'll form impressions
      related to everything from the speaker's physical and personality characteristics
      to his or her intellectual ability, and eventually even generalize their
      impressions to include the office that the speaker represents. If you want to
      improve your vocal image, you must first be aware of exactly what that image is.
      There are two factors that combine to create a vocal impression--the speaker's
      physical vocal tools and the sound that is created by them. The five physical
      tools involved are the lungs, vocal cords, throat, mouth and ears. At each stage
      in the sound production process, we can easily fall into negative habits and lazy
      patterns if we're not careful. Although we can't do much about our physical voice
      mechanism, we can certainly exercise a great deal of control over how our voice
      is used. A strong, confident voice is an essential part of effective
      interpersonal communication. If you want to project an image of confidence and
      professionalism, don't overlook the subtle benefits of effective vocal power.

PMID- 8868167
TI  - The Internet: your bridge to world dentistry.

PMID- 8868168
TI  - Multimedia dental patient education systems.

PMID- 8868169
TI  - Indebtedness of dental school graduates in Canada: mortgaged futures.
AB  - The debt level of graduating dental students is increasing annually. Six of
      Canada's 10 dental schools responded to a survey designed to ascertain the level
      of student debt on entering and graduating from dental school. For the academic
      year 1993-94, the average starting debt for students was $2,013.89 and the
      average graduating debt was $25,671.30. On average, dental students accumulated
      more than $23,600 in debt while pursuing their dental education. Of those
      students who completed the survey, 57.89 per cent relied on their parents for
      assistance, and 76.69 per cent received student/government loans. The level of
      student debt was independent of age, gender and parents' income.

PMID- 8868170
TI  - Chemical burns of the oral mucosa: report of a case.
AB  - Clinical diagnosis of a chemical burn of the oral mucous membranes may be a
      diagnostic challenge. This article's intent is to illustrate the typical
      appearance of a chemical mucosal burn and to increase awareness of the various
      compounds which, when in contact with the mucous membranes, can result in a burn.
      The authors present a case involving a self-inflicted chemical injury of the oral
      mucous membranes and illustrate how the submission of an easily-obtained tissue
      specimen for pathologic examination may aid in the diagnosis. Because these
      superficial tissues can be obtained and submitted without the need for local
      anesthetic, pathologic examination is a quick, easy, and valuable diagnostic test
      when a patient's history is difficult to obtain or intentionally misleading.

PMID- 8868171
TI  - [Applicability of the R.E.A.L. classification of non-Hodgkin's lymphoma in
      clinical practice].
AB  - Recent classifications of Non-Hodgkin's lymphomas include pathologic entities
      that should be defined by a multiparameter (morphologic, phenotypic and
      molecular) characterization. The feasibility of such an approach in routine
      pathology practice is discussed, based on the specific organization of the
      pathology laboratories.

PMID- 8868172
TI  - [The Internet for medical research].
AB  - In every scientific field, research is based on communication and information
      share: scientific journals and meetings meet this natural need. Recently, there
      was a growing development of a new tool enabling knowledge share in fast and
      efficient manner: the Internet computer network. Now, Internet connects the
      majority of world scientific organizations and the number of network users is
      more and more increasing. In particular, the information hypermedia connection
      called World Wide Web, is very useful for scientific purposes. In addition, as
      biomedical informations are also available on Internet, it becomes an important
      and irreplaceable resource on physician's desk.

PMID- 8868173
TI  - Diagnostic and biological determinants in undifferentiated and poorly
      differentiated ovarian carcinomas.
AB  - Six ovarian undifferentiated carcinomas (UCs) and 19 poorly differentiated serous
      (14 cases) and endometrioid (5 cases) carcinomas with areas of solid diffuse
      carcinomas have been considered for the study. Pathological findings were
      analyzed in conjunction with molecular analysis concerning the structure and
      expression of nm23-H1 gene. Differences in the frequency of loss of
      heterozigosity (LOH) of this gene have been observed between the two groups, UCs
      displaying lower percentage of LOH (1/5) as compared to poorly differentiated
      tumors (17/17). The remaining 3 cases (1 UC and 2 poorly differentiated
      carcinomas) were homozygotes, i.e., noninformative. UCs might occur as a
      consequence of cellular dedifferentiation, being at the end of the
      differentiation spectrum of epithelial ovarian tumors. Nevertheless, this study
      suggests that, in a fraction of cases, UCs could represent a distinct entity not
      involved in the malignant progression, associated with peculiar DNA anomalies,
      one possibly being that of the nm23-H1 deletion. In other words, a noticeable
      subset of UCs, not harboring nm23-H1 alterations, may be histologically
      uncommitted "ab initio". Moreover, nm23-H1 LOHs could be considered early events
      in the ovarian carcinogenesis, because similar molecular patterns were found both
      in primary and metastatic sites of the same tumor.

PMID- 8868174
TI  - Immunohistochemical detection of p53 protein in tumours of the central nervous
      system.
AB  - The results of immunohistochemical detection of p53 protein in a large variety of
      CNS neoplasms with the polyclonal antiserum CM1 are presented. Immunoreactivity
      in at least several cells were regularly found in astrocytic neoplasms including
      glioblastomas; it was also frequent in medulloblastomas and oligodendrogliomas
      and could be found in more than 50% of acoustic schwannomas and
      esthesioneuroblastomas. Meningiomas also showed several immunoreactive cells in
      about 40% of the cases. Certain neuronal/neuronal-glial tumours (such as central
      neurocytomas, dysembryoplastic neuroepithelial tumours, gangliocytomas,
      dysplastic gangliocytomas of the cerebellum etc.) were consistently negative,
      whereas gangliogliomas (with the exception of the regularly positive desmoplastic
      gangliogliomas) very rarely displayed immunoreactive glial cells. Positive
      findings, however, seem to be more frequent in anaplastic gangliogliomas where
      they may be of prognostic significance. The same may be valid in ependymomas. The
      underlying mechanism for p53 immunopositivity, however, can be very heterogeneous
      and possibly even contrary (either accumulation of inactive mutant protein or
      detection of active wild-type protein), therefore isolated immunohistochemical
      findings call for very cautious interpretation.

PMID- 8868175
TI  - [Male breast cancer. Histochemical and flow cytometry analysis of 6 cases].
AB  - The authors studied immunohistochemical and flow cytometric parameters of 6 male
      breast carcinomas. All patients were ER positive and frequency of aneuplody was
      66%. Diploid tumors showed low proliferative activity and S-phase fraction < 3%.

PMID- 8868176
TI  - [Breast carcinoma metastatic to meningioma: review of the literature and
      description of 2 new cases].
AB  - Two cases of breast carcinoma metastatic to meningioma are described in patients
      69 and 62 years old respectively. MATERIAL AND METHODS: Cases were documented by
      radiological, histological and immunohistochemical techniques. RESULTS: Both
      meningiomas contained an invasive duct carcinoma of the breast, one of which was
      apocrine in nature. CONCLUSION: It is suggested that metastasis to meningioma is
      not so rare as it appears from the literature.

PMID- 8868177
TI  - [Crohn's disease and intestinal carcinoma: presentation of 2 cases and review of
      the literature].
AB  - We present the cases of two patients with Crohn's disease with consequent
      adenocarcinoma of the bowel. The first patient underwent an ileo-colic bypass 23
      years before, a mucinous adenocarcinoma (Duke's stage C) was found on the
      anastomotic tract and on the excluded bowel, in areas within histologically
      recognizable Crohn's disease. In the second patient both the adenocarcinoma
      (Duke's stage C) of the transverse colon and the Crohn's disease (without any
      clinical evidence) in active phase has been found at the same time. We underline
      that such association seems to be not so rare as it seemed in the past. Accurate
      observation of patients, long time sufferers from the Crohn's disease, is advised
      to single out possible neoplastic complications at an early stage.

PMID- 8868179
TI  - Experimental acute hepatic vein occlusion: histological observations in the rat.
AB  - The histological consequences of hepatic venous outflow obstruction were studied
      in the rat. Circulatory changes as venous congestion and interstitial fluid
      accumulation are followed by signs of cellular damage progressing till
      hemorrhagic infiltration and focal necrosis. These are quite completely
      reversible in a period of 15 days.

PMID- 8868178
TI  - [Solitary capillary hemangioblastoma, cellular variant. Clinical, radiological,
      and anatomo-pathological study of 2 cases].
AB  - Two cases of the rare cellular variant of the solitary capillary
      haemangioblastoma are reported. On MR study both tumors appeared as cerebellar
      contrast-enhancing masses, without evidence of intra- or perilesional blood
      vessels. Histologically, they showed compact groups of polygonal or rectangular
      cells separated by compressed small capillaries. There were no reticulin fibres
      among cell clusters. The stromal cells were found to be immunopositive for neuron
      specific enolase (NSE), factor VIII-related antigen (von Wille-brand factor),
      Ulex europaeus lectin, and glial frillary acidic protein (GFAP). The findings are
      discussed in light of the pertinent literature.

PMID- 8868180
TI  - Empyema with malakoplakic-like lesions by Rhodococcus equi as a presentation of
      HIV infection.
AB  - Rhodococcus equi (Corynebacterium equi) is an aerobic actinomycetes, well
      described as a cause of pulmonary infection in different animals as horses, pigs
      and cows. This pathogen has a coccobacillar aspect and a variable acid-fast stain
      in tissues. Rare cases of human infection by Rhodococcus species were described,
      the majority by Rhodococcus equi, especially in patients with immunodeficiency
      syndrome (AIDS) in advanced stages of the disease. Usually the diagnosis of
      infections by Rhodococcus species is performed by positive blood or
      bronchoalveolar lavage cultures. Here we described a case of a pleuro-pulmonary
      infection by Rhodococcus equi, with malakoplakic-like lesions, that was the first
      manifestation of AIDS, whose diagnosis was performed by pleural biopsy (acid-fast
      bacteria with a variable coccobacillar aspect inside macrophages) and pleural
      fluid culture.

PMID- 8868181
TI  - S-100 protein expression in a case of elastofibroma dorsi.
AB  - Elastofibroma is a rare tumorlike process that manifests as slowly growing, solid
      mass in the subscapular region of elderly persons. Histologically, it is
      characterized by the presence of fibrous connective tissue in which eosinophilic
      fibers and globular masses, stained by the elastic tissue stains, are
      interspersed. We report the immunohistochemical study of the cellular component
      in a case of subscapular elastofibroma in a 41-year-old man. An unexpected
      immunoreactivity for S-100 protein was detected in most fibroblast-like cells. S
      100 protein expression may be related to a chondroid metaplasia of fibroblast
      like cells in response to the continuous traumatic process occuring during the
      friction between the scapula and the underlying chest wall.

PMID- 8868182
TI  - Squamous carcinoma of the epiglottis with sebaceous differentiation. Report of a
      case.
AB  - A case of squamous cell carcinoma with sebaceous metaplasia arising in the
      epiglottis is reported. Extracutaneous neoplasms that show sebaceous
      differentiation have been mainly described in the major salivary glands. To date
      only one case of prominent sebaceous differentiation in a carcinoma arising in
      the vallecula has been reported. In the present paper we describe a similar case
      arising in the larynx.

PMID- 8868184
TI  - Angiomyxoma of larynx. Report of one case of a myxoid fibrohistiocytic lesion.
AB  - This paper describes an angiomyxoid tumour in a previously unreported
      localization. The neoplasm has been excised and microscopic study disclosed an
      association of the angiomyxoid proliferation with an epithelial inclusion cyst.
      The tumour recurrence consisted of a large mass of purely angiomyxoid tissue.
      Electron microscopic study revealed the fibrohistiocytic features of the
      proliferating cells. This study along with immunocytochemistry ruled out nervous
      sheat and smooth muscle differentiation. We consider this tumour as the laryngeal
      counterpart of the so-called aggressive angiomyxoma of pelvic peritoneum and
      compare it with the group of lesions collected under the name of superficial
      angiomyxomas.

PMID- 8868183
TI  - [Myoepithelial-epithelial carcinoma of the parotid: cyto-histological description
      of a case].
AB  - We report a case of epithelial-myoepithelial carcinoma of the parotid gland
      arised in a 72 years-old woman, in which the diagnosis was suspected on fine
      needle aspiration and confirmed on surgical specimen. Immunohistochemical
      evidence for the dual differentiation (glandular and myoepithelial) of the tumour
      was obtained both on surgical specimen and cytological inclusion. Morphological
      features and proliferating index (MIB1) analysis suggest that this case is an
      intermediate grade malignant neoplasm. Main differential diagnosis of the
      epithelial-myoepithelial carcinoma with predominantly clear cell tumours of the
      salivary glands were discussed.

PMID- 8868185
TI  - Retroperitoneal cystic neuroendocrine tumor. A case report.
AB  - A 21 cm retroperitoneal cystic mass was excised from a 71 year old woman. The
      cyst was filled with a hemorrhagic fluid and contained a 5 cm parietal
      hemorrhagic nodule. On histology, the nodule was composed of a uniform population
      of round cells arranged in trabeculae and nests. The neoplastic cells were
      immunoreactive to cytokeratin, EMA, NSE, chromogranin A, pancreatic polypeptide
      (PP) and Gastrin (G). Ultrastructural observation of neurosecretory granules
      confirmed the neuroendocrine nature of the tumor. No other lesions were detected
      and a diagnosis of primary epithelial neuroendocrine tumor was rendered. The
      histogenesis of the tumor including the possibility of a paraganglionic origin is
      discussed.

PMID- 8868186
TI  - [Olfactory neuroblastoma. Presentation of a case].
AB  - Olfactory neuroblastoma is an uncommon and hardly diagnosable neoplasm. The
      conventional histologic analysis allows generally a diagnosis of undifferentiated
      carcinoma. The immunohistochemical procedures, particularly the S-100 Protein and
      the Enolase Neuron-Specific, may contribute to define the diagnosis as well as in
      a patient recently observed by the authors.

PMID- 8868187
TI  - [Association of a granular-cell tumor with an epidermoid carcinoma of the
      esophagus].
AB  - Granular cell tumor is a rare tumor, described for the first time by Abrikossoff
      in 1926. Occurrence in the esophagus is rare (1.6% of digestive localizations).
      This paper reports a case of granular cell tumour associated with squamous cell
      carcinoma of the esophagus.

PMID- 8868188
TI  - Pseudosarcoma of the urinary bladder.
AB  - A case of pseudosarcoma of the urinary bladder is described in a woman aged 23.
      The tumor presenting with symptoms of cystitis arised in the left wall and
      invaded vesical cavity and pelvis. Histological, histochemical,
      immunohistochemical and electron microscope studies revealed a fibroblastic and
      myofibroblastic proliferation with atypias, accompanied by inflammatory
      infiltrates and rich vascularity. The tumor was furthermore characterized by
      extensive necrosis, involving the muscularis propria, and infiltrated the
      perivesical fat. The favourable outcome four years after partial cystectomy
      suggests the diagnosis of pseudosarcoma. The differential diagnosis and the
      pathogenesis of this rare lesion is discussed.

PMID- 8868189
TI  - Primary vesical malignant lymphoma of histiocytes detected by urine cytology.
AB  - Urinary cytology performed in a woman aged 64 revealed an uncommon cell
      population with malignant features highly suggestive of a lymphoma. Histologic
      and immunohistochemical investigations of a polypoid endovesical mass surgically
      resected showed a lymphoma of histiocytes in the lamina propria of the bladder
      wall. Clinical, operative and pathologic staging demonstrated that the tumor was
      confined to bladder. The case repeats the typical features of primary vesical
      lymphoma reported in the literature. The favourable follow up six years after
      surgery confirms the good prognosis of bladder Iymphoma treated by aggressive
      therapy.

PMID- 8868190
TI  - [Galen's oncology].
AB  - "Claudius Galenus" is the Author of "De tumoribus praeter naturam". The book was
      studied on the original Greek text with Latin version edited by K.G. Kuhn ("Opera
      omnia Claudii Galeni": VII, 705-732). This Galen's clinical and pathological
      oncology was examined as far as categorization, classification, morphology,
      etiology, pathogenesis, morphogenesis, topography, behaviour (with related
      therapeutic and prognostic implications) and terminology are concerned. Problems,
      aspects and concepts, more or less clarified by Galen, were extensively discussed
      with special reference to the Galen's scientific knowledge and compared with the
      modern oncology.

PMID- 8868191
TI  - [Toxoplasmosis in patients with AIDS].
AB  - Toxoplasmosis in patients with AIDS has specific traits, differentiating it from
      cases occurring in immuno-competent persons. Some features of the parasite, which
      are important for the clinical outcome of the disease, and the epidemiology,
      histopathology and clinical picture of toxoplasmosis in conditions of immuno
      deficiency are discussed in the paper.

PMID- 8868192
TI  - [Correlation of clinical and morphological diagnoses in 55 fatal AIDS cases].
AB  - Pathomorphological studies were performed in 60 HIV-infected patients and the
      accuracy of clinical diagnoses of infections and neoplasms was evaluated. In 5
      cases clinical diagnosis of AIDS was not confirmed at autopsy. 114 infections and
      neoplasms were found in 55 AIDS-patients, of these 80 (70%) were not diagnosed
      clinically. Clinical diagnosis of the cause of death was consistent with
      morphological findings in 24 AIDS cases (45.5%). The results justify a plea for a
      close co-operation of clinicians, microbiologists and pathologists to improve the
      accuracy of clinical diagnoses in AIDS patients. In a fatal case of AIDS a post
      mortem study should always be performed.

PMID- 8868193
TI  - [Occurrence and clinical picture of Clostridium difficile infections after
      antibiotic therapy].
AB  - 39 patients with colon bowel inflammatory by C. difficile infection after
      antibioticotherapy were treated. The causes of antibioticotherapy most frequently
      former infection of the upper respiratory tract. The C. difficile infection were
      most frequently before therapy: poliantibiotics, Cephalosporins II generations
      and Linkomycin. In diagnosis of C. difficile infection the Enzyme Immuno
      Fluorescence Test were practical utility confirmed. The symphtomaticotherapy
      patients with slight course of ills were sufficiently. The therapy of
      Metronidazol or/and Colestyramine in patients with mild or highly course of ills
      were efficacious.

PMID- 8868194
TI  - [Observation of patients with malaria hospitalized during the years 1980-1993 in
      the Clinic of Infectious Diseases in Szczecin].
AB  - Thirty five patients with imported malaria were hospitalised in a period of 1980
      93 in Department of Infectious Diseases of Pomeranian Medical School, Szczecin,
      Poland. The diagnosis of malaria was established on a base of clinical feature,
      the presence of Plasmodium in peripharal blood smears and, in some cases, on
      positive serological tests. Thirty two patients were Polish citizens, and three
      persons were foreigners. Malaria was caused mostly by invasion of Plasmodium
      falciparum (62.8), then P. vivax (31, 4), in 1 case--P. ovale and 1 case--mixed
      invasion occurred (P. falciparum and P. vivax). The majority of cases caused by
      P. falciparum were imported from Central Africa. Invasions of P. vivax were
      brought from North Africa, India and Middle East. Malaria in Polish patients was
      connected with occupational exposure and lack of proper antimalarial prophylaxis
      was obvious. A clinical course of disease was serious, with one mortal case.
      Fever, headache, abdominal pain, weakness, jaundice, insomnia were main
      complaints. Anemia, leucopenia, thrombocytopenia, hyperbilirubinemia,
      hypertransaminasemia and high serum concentration of urea were observed. A level
      of parasitemia in peripheral blood varied from minimal to very high (22.5%) in
      cases of P. falciparum invasions. In treatment chloroquine, fansidar, quinine,
      primaquine, halfan were used.

PMID- 8868195
TI  - [Epidemiologic situation of Lyme borreliosis in Europe].
AB  - The aim of paper was to present epidemiological data related to Lyme borreliosis
      (LB), including reservoirs and transmission of Borrelia burgdorferi (B.b.).
      Incidence of the disease in Europe was evaluated through review of literature
      data. Morbidity exceeding 100 cases per 100,000 inhabitants per year observed in
      central Europe, indicate the highest prevalence of LB in this part of continent.
      Prevalence of antibodies against B.b. among blood donors in particular european
      countries varied from 0 to 18.8%, whereas in high risk groups (mostly forestry
      workers) it was 5.7-71%. Diagnostical criterions for surveillance purpose in
      Europe, which should be established in future, make possible to complete
      epidemiological data related to LB.

PMID- 8868196
TI  - [Evaluation of antitoxin and antibacterial activity of human preparations of
      normal immunoglobulin. I. Level of tetanus antitoxin in preparations of IMIG and
      IVIG].
AB  - The level of anti-tetanus antibodies were measured in 791 lots of IMIG and 330
      lots of IVIG of human normal gamma globulin. The antibody levels varied 15-80
      IU/ml of IMIG lots and 5-20 IU/ml of IVIG lots. Every lot of human normal gamma
      globulin (IMIG or IVIG) having high anti-tetanus activity may be an acceptable
      alternative to specific tetanus immune globulin.

PMID- 8868197
TI  - [Infectious mononucleosis with IgM antibodies against cytomegalovirus].
AB  - In four of studied children (age 3-12 yrs) with serologically confirmed
      infectious mononucleosis we found IgM antibodies to CMV. This can be explained by
      coincidence of both infections or by nonspecific stimulation of B lymphocytes in
      the course of mononucleosis. Disappearance of IgM antibodies to CMV after 3
      months, and concomitant presence of IgG antibodies after 6 months suggests the
      former.

PMID- 8868198
TI  - [Hearing loss during the course of mumps].
AB  - Unilateral deafness as a permanent hearing injury in a patient aged 15 years with
      mumps is presented. Attention is paid to uncommon occurence of that complication
      in the course of the disease and to necessarity of taking into consideration
      mumps virus among other ototoxic infectious factors.

PMID- 8868199
TI  - [A case of bacterial endocarditis (BZW) caused by Corynebacterium group JK].
AB  - A case of bacterial endocarditis caused by Corynebacterium group JK treated with
      penicillin, chloramphenicol and gentamycin has been described. Finally the
      artificial aortal valve has been implanted.

PMID- 8868200
TI  - [Assessment of cancer risk in the general population of Poland due to asbestos
      exposure. I. Basis of methodology].
AB  - Two mathematical models facilitating calculation of cancer risk in people exposed
      to asbestos dust in the communal environment are discussed. The first helps
      determine a dose-response relationships when lung cancer is the exposure effect
      whereas the second permits calculating the probability of pleural or peritoneal
      mesotheliomas induction based on the level of asbestos exposure. In the case of
      lung cancer, the exposure is measured as a cummulated dose which equals to a
      product of an average concentration of asbestos fibres in 1 ml of the air
      multiplied by duration of exposure (in years). Thus determined relationship
      between asbestos exposure and the risk involved is a linear function. The effect
      of smoking, which undoubtedly accounts for lung cancer induction, is an element
      of the assessment in this model. The relationship between the risk of
      mesothelioma and exposure level, which is a non-linear function, is associated
      with the duration of exposure (in years) and the number of years since first
      asbestos exposure, however, it is not related to the age of person when first
      exposure occured or smoking habit. It may assumed that, in the case of
      environmental exposures, the level of exposure could be measured by the duration
      of exposure to a determined concentration (the exposure starts at birth to be
      continued throughout the whole lifetime until death). The models presented allow
      forecasting cancer risk based on the adopted level and duration of exposure to
      asbestos dust.

PMID- 8868201
TI  - [Assessment of lung cancer risk due to environmental asbestos dust exposure in
      the general population].
AB  - Assessment of lung cancer risk due to environmental asbestos dust exposure in the
      general population was based on the model of risk extrapolation from the
      occupational (in asbestos-cement plant) to the environmental concentrations. 24-h
      determinations of asbestos fibre concentrations in the air varied considerably,
      from 0.4 f/l to 4.6 f/l. The lung cancer risk due to environmental exposure of
      the general population to asbestos dust has been estimated to be 22 cases p.a.
      This seems to be very low, considering that the total number of deaths from lung
      cancer in Poland in 1992 was about 17.5 thousand. The environmental asbestos
      exposures and their health effects are limited mainly to the areas located in the
      vicinity of asbestos plants and are attributable primarily to improper
      utilization of the plant wastes (for example as the surface of local roads and
      sports grounds at schools) and their unathorized disposal. The incidence of
      pleural mesothelioma among the inhabitants of those areas seems to be endemic.
      The endemic character of pleural mesothelioma occurrence has been recently
      revealed in the vicinity of one of major Polish asbestos and cement plant.

PMID- 8868202
TI  - [Domestic factors and respiratory symptoms in children].
AB  - The purpose of the analysis was to evaluate an association between selected
      factors of home environment and respiratory symptoms (wheezing/whistling) and
      asthma diagnosed by physician in 4333 children of age 7-8 years in Poznan. The
      data were collected within the scope of the EU funded multinational SAVIAH study.
      It was found that presence of the symptoms as well as asthma were significantly
      associated with presence of damp spots and/or mould at home and disturbance by
      traffic fumes and/or noise at home. The association of respiratory symptoms with
      ETS and presence of pets was less clear.

PMID- 8868203
TI  - [Changes in hospitalization frequency for circulatory system diseases, injuries,
      poisonings and neoplasms in Poland in the years 1979-1993].
AB  - For years, the main cause of deaths in Polish population have been malfunctions
      of the circulatory system diseases, injury and poisoning, malignant neoplasm. It
      is causing more and more concern, especially of circulatory system diseases. Lot
      of different factors affect mortality statistics, one off then is accessibility
      to the use hospital care. Changes in the frequency of hospital discharge, at ICD
      9: (390-459), (401-405), (410-414), (430-438), (440), (140-208), (162), (174),
      (180), (800-999) in the year 1979-1993, have been discussed in this analyzes.

PMID- 8868204
TI  - [Model of a national system for surveillance of Lyme borreliosis (LB)--Extraction
      of materials from the World Health Organization working group (SOZ) 20
      22.VI.1995].

PMID- 8868205
TI  - Hostility in heroin abusers subtypes: fluoxetine and naltrexone treatment.
AB  - 1. Substance abusers subtypes have been identified considering underlying
      psychobiological disorder, familial factors, age of onset, legal problems and
      drug of choice. 2. In the present study the authors submitted 98 male heroin
      addicted individuals (age 19-28 y) to the Buss Durkee Hostility Inventory
      (Italian version) and a structured interview concerning social and clinical
      history; legal problems, age of onset of drug abuse, drug of choice. 3.
      Serotonergic system sensitivity was evaluated with fenfluramine challenge for PRL
      assay. 4. Thirty two patients (group A) showed high score for resentment and
      guilt at BDHI (hostility in), low rate of legal problems, late age of onset,
      preference for heroin and alcohol. Twenty nine patients (group B) showed high
      score for assault and irritability at BDHI (hostility out), high rate of legal
      problems, early age of onset, preference for heroin and cocaine. The other 37
      patients (group C) showed aggression score in the normal range at BDHI, no legal
      problems, late onset of substance abuse, preference for heroin only. 5. PRL
      responses was blunted in group A (p < 0.001) and significantly decreased in group
      B (p < 0.05). PRL plasma levels were inversely correlated with HRSD scores. 6.
      All the patients were included in a treatment protocol with fluoxetine and
      naltrexone or placebo and naltrexone for 6 months. 7. The treatment was effective
      in group A with a significant improvement of BDHI results and decrease of craving
      score, lower level of drop out, lower level of positive urine controls. No
      significant differences between fluoxetine and placebo effects have been
      evidenced in patients of group B and C. The present findings suggest that
      psychopharmacological approach to addiction needs a diagnostic screening for
      specific subtypes.

PMID- 8868206
TI  - The therapeutic role of naltrexone in negative symptom schizophrenia.
AB  - 1. Naltrexone (50 mg bid, p.o.) was administered in a double-blind fashion (with
      placebo control) to chronic schizophrenic patients who maintained their routine
      neuroleptic and anxiolytic therapy. 2. Both positive and negative symptom
      patients who received naltrexone improved with regard to symptoms involving
      deterioration and social withdrawal. No significant amelioration was recorded in
      subjects assuming placebo relative to the same psychopathological areas. 3.
      Favourable results were obtained mainly from patients affected by negative
      symptom schizophrenia. 4. Naltrexone may have acted by direct or indirect
      neurochemical mechanisms related to negative symptom schizophrenia.

PMID- 8868207
TI  - A juvenile case of frontotemporal dementia: neurochemical and neuropathological
      investigations.
AB  - 1. An autopsy case of frontotemporal dementia with onset at the early age of 28
      years is reported. 2. The neuropathological features consisted of limited, knife
      like frontotemporal atrophy with severe neuronal loss, spongiform change and
      gliosis, which is compatible with the frontotemporal dementia. 3. Biochemical
      determinations disclosed that biogenic amines and their metabolites, predominant
      in the dopaminergic markers, were depleted in the damaged regions. 4. Since
      biochemical data in frontotemporal dementia are few in previous studies, it will
      be determined whether these biochemical changes are characteristic for the
      juvenile type of frontotemporal dementia or not.

PMID- 8868208
TI  - Mitogen stimulated rise of intracellular calcium concentration in single T
      lymphocytes from patients with major depression is reduced.
AB  - 1. The authors investigated the signal transduction in T-lymphocytes as a
      peripheral model for central neurons. 2. Intracellular free calcium concentration
      [Ca2+]i was measured using fura 2 in T-lymphocytes from 6 patients with major
      depression during and after depression and from 6 healthy controls. Patients were
      treated with interpersonal therapy (IPT) but not with psychotropic medication. 3.
      Phytohemagglutinin (PHA) triggers an oscillatory [Ca2+]i signal in human T
      lymphocytes. This implies two mechanisms for [Ca2+]i regulation: inositol
      phophate (IP) mediated release from intracellular stores and [Ca2+]i influx from
      the extracellular medium. 4. PHA stimulates 49% of T cells from controls but only
      17% of T cells from depressed patients. This finding explains previous results
      from cells in suspension indicating that [Ca2+]i signals after PHA-stimulation
      are reduced in cells from depressed patients. 5. Cells from depressed patients
      show less [Ca2+]i oscillations. Normal oscillation patterns are restored after
      clinical recovery from depression. 6. Thus altered [Ca2+]i oscillations in T
      lymphocytes are a state phenomenon and may give us clues where to search for
      altered cellular mechanisms during depression.

PMID- 8868209
TI  - An early lesion of the lateral septal nuclei produces changes in the forced swim
      test depending on gender.
AB  - 1. Several pharmacological maneuvers in very young rats produce later changes
      resembling human depression. 2. Rats were submitted to a wide lesion in lateral
      septal region at 8th day after birth and forced to swim at maturity. 3. Male
      lesioned group showed the highest amount of immobility; whereas, female sham
      lesion group showed a greater response to treatments. 4. A gender-dependent
      sensitivity to early lateral septal nucleus lesions and to antidepressants are
      concluded.

PMID- 8868210
TI  - Regulation of dopamine release and metabolism in rat striatum in vivo: effects of
      dopamine receptor antagonists.
AB  - 1. The acute effects of some of typical and atypical antipsychotic drugs on the
      dopamine release and metabolism in the dorsal striatum of freely moving rats were
      studied using transcerebral microdialysis technique. 2. Classical neuroleptic
      drugs haloperidol (0.05, 0.1 and 0.2 mg/kg), thioproperazine (0.1, 0.2 and 0.4
      mg/kg) and spiperone (0.02, 0.04 and 0.07 mg/kg) administered i.p. induced
      pronounced elevation of extracellular level of 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA) up to 250-300% to basal level while producing
      less increase in that of dopamine (DA) (up to 150-170%). 3. Atypical neuroleptics
      clozapine and thioridazine (both 2, 5 and 20 mg/kg) increased striatal DA release
      and DOPAC level approximately at the same degree (maximally up to 200% and 160%,
      respectively). 4. Dopamine D3 receptor and autoreceptor preferring antagonists
      (+)-UH232 and (+)-AJ76 (both 4, 7 and 14 mg/kg) more potently increased DA
      release in comparison with DOPAC dialysate level (+)-AJ76 elevated DA level
      maximally up to 330%, DOPAC-up to 250%). 5. The features of typical and atypical
      neuroleptics in preferential action on DA release or DOPAC output were observed
      in all doses of the drugs studied. 6. The ability of the drugs to affect
      preferentially DA release or DOPAC extracellular level in rat striatum correlates
      to their relative affinities at D3 and D2 DA receptors. 7. It is concluded that
      typical and atypical antipsychotic drugs might be clearly distinguished on the
      basis of their ability to affect preferentially DA synthesis/metabolism or
      release in rat dorsal striatum in vivo.

PMID- 8868211
TI  - Development of an animal model of fluoxetine akathisia.
AB  - 1. Akathisia describes the pattern of intense inner restlessness often associated
      with neuroleptic and antidepressant treatment. 2. The authors postulated that
      drug-induced akathisia would be characterized by more position changes and less
      time spent immobile, in the absence of significant increase in ambulation. In
      contrast, a psychomotor stimulant would produce both activation and ambulation.
      3. Procedures and instruments were developed to test this hypothesis. Adult rats
      were habituated for 72 hours to the testing environment, and their precise
      pattern of movements was tracked and recorded (10 reading per second; resolution
      0.04 mm) by an infrared motion analysis system. Activity was recorded for a 90
      min period after a single injection of sub-stereotypic doses of d-amphetamine (0,
      0.3, 1.0 mg/kg) or racemic fluoxetine (0, 3.0, 10.0, 20.0, or 30.0 mg/kg, s.c.).
      4. Amphetamine produced both activation and ambulation. Activation was indicated
      by a decrease in time spent immobile, and an increase in the temporal scaling
      exponent, which reflects the degree the animal is "acting' in its environment,
      and the number of position changes. Enhanced locomotion was inferred from marked
      increases in both the total distance traversed and the ratio of forward movements
      to-reversals and a decrease in the spatial scaling exponent, indicative of a less
      complex and more linear movement pattern. 5. Fluoxetine caused animals to spend
      more time active, but exerted little effect on locomotion. Activation was
      indicated by a decrease in time spent immobile and an increase in the temporal
      scaling exponent and number of position changes. Fluoxetine failed to
      significantly effect either the ratio of forward movements-to-reversals or the
      spatial scaling exponent. 6. These findings provide an operational definition and
      methodology that can be used to differentiate between psychostimulant effects and
      akathisic effects. This approach may have utility for screening drugs for
      akathisic potential, for exploring underlying mechanisms, and for developing
      novel treatments.

PMID- 8868212
TI  - Neuroleptic malignant syndrome after neuroleptic discontinuation.
AB  - 1. Neuroleptic withdrawal can cause autonomic and behavioral symptoms (nausea,
      vomiting, diarrhea, diaphoresis, myalgia, anxiety, restlessness) and movement
      disorders (withdrawal emergent parkinsonism, withdrawal dyskinesia, covert
      dyskinesia). 2. Neuroleptic malignant syndrome (NMS) is a rare but extremely
      severe adverse reaction to neuroleptic drugs characterized by extrapyramidal and
      autonomic symptoms, altered level of consciousness and abnormal laboratory
      findings. 3. Withdrawal neuroleptic malignant syndrome, though an even rarer
      condition (only 7 cases reported to date), should alert to consider the
      possibility that abrupt neuroleptic discontinuation can be complicated by NMS. 4.
      The pathophysiology of withdrawal medical symptoms may be related to a
      cholinergic rebound; withdrawal neuroleptic malignant syndrome may be attributed
      to an "imbalance" in the dopaminergic system. 5. The authors report two cases of
      NMS precipitated by the abrupt withdrawal of neuroleptic drugs.

PMID- 8868213
TI  - The mineralization of crystalline inorganic components in Japanese serow horn.
AB  - The Japanese serow (Capricornis crispus) is protected as a special natural
      monument in Japan. The ring count of the soft X-ray photographs of Japanese serow
      horn was found to be a useful criteria to determine the ages exactly. The
      mineralization process in Japanese serow horn was examined microscopic, ICP and X
      ray diffraction methods. The incremental lines appeared as light and dark layers
      in the section stained for fuchsin and methylen blue. Mineral depositions were
      observed among the keratin fibers, no matrix vesicle in the electron dense
      regions. X-ray diffraction pattern of crystalline inorganic components in
      Japanese serow horn was determined as beta-tricalcium phosphate (TCP),
      hydroxyapatite (HA) and unknown phase. ICP measurement was also carried out. The
      horn contained trace elements of K besides Na, Ca, Fe and P. The Ca/P molar was
      found to be 2.9. The ratio was much higher than the theoretical value of HA.
      Presumably, keratin was the seed which might be related to mineralization and
      higher Ca activity was detected in the initial phase of epitaxial growth.
      Analytical results of the measurement of trace elements in Japanese serow horn by
      using ICP method seemed to be correlated with the evaluation of environmental
      conditions. The present study indicated that the mineralization of Japanese serow
      horn directly related with deposition Ca-deficient HA among the keratin fibers.

PMID- 8868214
TI  - Variation of the right subclavian artery as the last branch of the aortic arch in
      two Japanese cadavers.
AB  - Two anomalous cases of the right subclavian artery were found in Japanese
      cadavers. In both cases, the right subclavian artery arose from the posterior
      wall of the aortic arch as its last branch, and ran rightwards between the
      esophagus and the vertebral column. The cases described belong to type G of the
      Adachi-Williams-Nakagawa-Takemura classification of aortic arch branching
      patterns.

PMID- 8868215
TI  - Surface morphology of quail ovaries in late embryonic stages.
AB  - Embryonic quail ovaries were examined with a scanning electron microscope. The
      same as in many bird species, the quail ovary degenerated on the right side, and
      normal development occurred only on the left side. The surface of the developing
      left ovary had a rough appearance. The epithelial cell surface was extremely
      swollen with many globular protrusions, and the cell borders were lined by ridge
      like protrusions. On the other hand, the degenerating right ovarian surface was
      rather smooth in appearance. Each cell surface had a few short microvilli.
      Several stomata were found near the border between the ovary and mesonephros in
      the posterior region of the right ovary. The size and number of stomata were
      variable, but tended to increase in the later stages. These findings were
      compared with those in the chick ovary, and a discussion is included.

PMID- 8868216
TI  - Morphometric analyses and aging process of nerve fibers in the human spinal
      posterior funiculus.
AB  - The aim of the present study is to evaluate the size and number of axons in the
      human spinal cord nerve fibers according to the aging process, and, after
      conducting morphometry of histology preparations at different ages, to show some
      of the effects of aging on those fibers. We examined thirty-eight human spinal
      cords which had been taken from cadaver specimens (25 males and 13 females) aged
      from 41 to 97 years. The spinal segments were embedded in celloidin and sections
      were stained with Luxol fast blue-periodic acid-Schiff-hematoxylin (LPH). Highly
      enlarged images with a square eyepiece grid and oil-immersion lens were used to
      count the myelinated axons and to measure the axon transverse area in a unit area
      of the posterior funiculus at C6 level, with the help of a microscope equipped
      with a drawing tube, an electronic optical planimeter and a computer. Significant
      age-related linear decreases were found for all parameters. Our report may
      provide new information concerning the aging process of the human spinal cord. It
      revealed that a decrease in size and number of axons were one of the important
      changes occurring with the aging process in the human spinal posterior funiculus.

PMID- 8868217
TI  - Observation of the internal configuration of rat incisor odontoblasts by scanning
      electron microscopy using the AODO method.
AB  - The internal configuration of rat incisor odontoblasts was studied mainly by
      scanning electron microscopy (SEM) using the AODO method (low concentration
      aldehyde prefixation, osmium tetroxide postfixation, dimethyl sulfoxide (DMSO)
      freeze-fracture, osmium tetroxide maceration). The present SEM findings were
      compared with the results obtained by conventional transmission electron
      microscopy (TEM) of epon-embedded specimens. The following results were obtained:
      1) Functioning odontoblasts were characterized by a concentric, laminar rough
      endoplasmic reticulum (rER) with many long mitochondria interposed. 2) A network
      of tubular smooth endoplasmic reticulum (sER) was observed in the odontoblast
      process and distal portion of both functioning and resting odontoblasts. 3) The
      tubulo-vesicular elements which have been found to present a modified Golgi-GERL
      organelle with secretory and absorptive functions were demonstrated in both the
      functioning and resting odontoblasts. Structurally they consist of the sER
      network and strings of granules and vesicles. 4) Various types of cytoplasmic
      bodies, e.g., lysosomes, cytosomes and multivesicular bodies, related to the sER
      were also noted in both functioning and resting odontoblasts. 5) Microapocrine
      secretion of membranous vesicles of various sizes into the predentin and along
      the lateral branchings of odontoblast processes in the circumpulpal dentin was
      observed during the matrix apposition stage of the odontoblasts. The present
      morphological study revealed the three-dimensional configuration of the intra-
      and extra-cellular structures related to dentinogenesis by odontoblasts.

PMID- 8868218
TI  - Immunocytochemical evidence for the presence of prolactin in the plerocercoid of
      Ligula intestinalis (Cestoda: Pseudophyllidea).
AB  - Immunoreactivity to prolactin in the nervous system of the plerocercoid of Ligula
      intestinalis was demonstrated by immunocytochemical method. Numerous PRL
      immunoreactive perikarya with long varicose fibres were observed in the
      peripheral nervous system in the worm, mainly in the transversal muscle layer and
      medullary parenchyma of the midbody. A few fibres were found in the main nerve
      cords of the central nervous system. PRL positive neurons sent their processes to
      associate with the main nerve cords. The immunostaining terminals appeared in the
      subtegument region in the lateral border of the plerocercoid. The result
      indicates that PRL immunoreactivity is well-developed in the plerocercoid of the
      cestode. The significance of the localization of prolactin in the worm is
      discussed.

PMID- 8868219
TI  - Radon plateout on synthetic fibers as a possible risk factor in breast cancer.

PMID- 8868220
TI  - Comment on "uptake of chloroform by skin during short exposures to contaminated
      water".

PMID- 8868221
TI  - Major chemical accidents in industrializing countries: the socio-political
      amplification of risk.
AB  - Accidents in the chemical industry, such as those that took place in Seveso
      (1976) and Bhopal (1984), may kill or injure thousands of people, cause serious
      health hazards and irreversible environmental damage. The aim of this paper is to
      examine the ever-increasing risk of similar accidents becoming a frequent
      ocurrence in the so-called industrializing countries. Using figures from some of
      the worst chemical accidents in the last decades, data on the Bhopal disaster,
      and Brazil's social and institutional characteristics, we put forward the
      hypothesis that present social, political and economic structures in
      industrializing countries make these countries much more vulnerable to such
      accidents and create the type of setting where--if and when these accidents occur
      -they will have even more catastrophic consequences. The authors argue that only
      the transformation of local structures, and stronger technical cooperation
      between international organizations, industrialized and industrializing countries
      could reduce this vulnerability.

PMID- 8868222
TI  - A Monte Carlo procedure for the construction of complementary cumulative
      distribution functions for comparison with the EPA release limits for radioactive
      waste disposal.
AB  - A Monte Carlo procedure for the construction of complementary cumulative
      distribution functions (CCDFs) for comparison with the U.S. Environmental
      Protection Agency (EPA) release limits for radioactive waste disposal (40 CFR
      191, Subpart B) is described and illustrated with results from a recent
      performance assessment (PA) for the Waste Isolation Pilot Plant (WIPP). The Monte
      Carlo procedure produces CCDF estimates similar to those obtained with importance
      sampling in several recent PAs for the WIPP. The advantages of the Monte Carlo
      procedure over importance sampling include increased resolution in the
      calculation of probabilities for complex scenarios involving drilling intrusions
      and better use of the necessarily limited number of mechanistic calculations that
      underlie CCDF construction.

PMID- 8868223
TI  - Industry response to SARA Title III: pollution prevention, risk reduction, and
      risk communication.
AB  - This paper reports results from a survey designed to: (1) evaluate changes in
      industrial pollution prevention practices since the passage of the landmark
      environmental legislation, the Emergency Planning and Community Right-to-Know Act
      of 1986, also known as SARA Title III, and (2) identify those factors that may
      contribute to an industrial facility engaging in pollution prevention and risk
      communication activities. The survey was conducted under a Cooperative Agreement
      between the U.S. Environmental Protection Agency and the Columbia University
      Center for Risk Communication. Evidence from the survey indicates that a wide
      variety of waste and pollution reduction activities have been undertaken since
      passage of the Act. Virtually all facilities surveyed in the pulp and paper,
      chemical, and petroleum and refining industries reported that they had reduced
      pollutants or wastes on at least one of ten measures, including reducing toxic
      air emissions. Most facilities indicated paying more attention to pollution
      prevention activities as a result of SARA Title III and half reported that their
      communication activities have also increased.

PMID- 8868224
TI  - Risk-based environmental remediation: Bayesian Monte Carlo analysis and the
      expected value of sample information.
AB  - A methodology that simulates outcomes from future data collection programs,
      utilizes Bayesian Monte Carlo analysis to predict the resulting reduction in
      uncertainty in an environmental fate-and-transport model, and estimates the
      expected value of this reduction in uncertainty to a risk-based environmental
      remediation decision is illustrated considering polychlorinated biphenyl (PCB)
      sediment contamination and uptake by winter flounder in New Bedford Harbor, MA.
      The expected value of sample information (EVSI), the difference between the
      expected loss of the optimal decision based on the prior uncertainty analysis and
      the expected loss of the optimal decision from an updated information state, is
      calculated for several sampling plan. For the illustrative application we have
      posed, the EVSI for a sampling plan of two data points is $9.4 million, for five
      data points is $10.4 million, and for ten data points is $11.5 million. The EVSI
      for sampling plans involving larger numbers of data points is bounded by the
      expected value of perfect information, $15.6 million. A sensitivity analysis is
      conducted to examine the effect of selected model structure and parametric
      assumptions on the optimal decision and the EVSI. The optimal decision (total
      area to be dredged) is sensitive to the assumption of linearity between PCB
      sediment concentration and flounder PCB body burden and to the assumed
      relationship between area dredged and the harbor-wide average sediment PCB
      concentration; these assumptions also have a moderate impact on the computed
      EVSI. The EVSI is most sensitive to the unit cost of remediation and rather
      insensitive to the penalty cost associated with under-remediation.

PMID- 8868225
TI  - On the correlation coefficient between the TD50 and the MTD.
AB  - The existence of correlation between the carcinogenic potency and the maximum
      tolerated dose has been the subject of many investigations in recent years.
      Several attempts have been made to quantify this correlation in different
      bioassay experiments. By using some distributional assumptions, Krewski et al.
      derive an analytic expression for the coefficient of correlation between the
      carcinogenic potency TD50 and the maximum tolerated dose. Here, we discuss the
      deviation that may result in using their analytical expression. By taking a more
      general approach we derive an expression for the correlation coefficient which
      includes the result of Krewski et al. as a special case, and show that their
      expression may overestimate the correlation in some instances and yet
      underestimate the correlation in other instances. The proposed method is
      illustrated by application to a real dataset.

PMID- 8868226
TI  - Field measurement of dermal soil loading attributable to various activities:
      implications for exposure assessment.
AB  - Estimates of soil adherence to skin are required for assessment of dermal
      exposures to contaminants in soils. Previously available estimates depend heavily
      on indirect measurements and/or artificial activities and reflect sampling of
      hands only. Results are presented here from direct measurement of soil loading on
      skin surfaces of volunteers before and after normal occupational and recreational
      activities that might reasonably be expected to lead to soil contact. Skin
      surfaces assayed included hands, forearms, lower legs, faces and/or feet.
      Observed hand loadings vary over five orders of magnitude (roughly from 10(-3) to
      10(2) mg/cm2) and are dependent upon type of activity. Hand loadings within the
      current default range of 0.2 to 1.0 mg/cm2 were produced by activities providing
      opportunity for relatively vigorous soil contact (rugby, farming). Loadings less
      than 0.2 mg/cm2 were found on hands following activities presenting less
      opportunity for direct soil contact (soccer, professional grounds maintenance)
      and on other body parts under many conditions. The default range does not,
      however, represent a worst case. Children playing in mud on the shore of a lake
      generated geometric mean loadings well in excess of 1 mg/cm2 on hands, arms,
      legs, and feet. Post-activity average loadings on hands were typically higher
      than average loadings on other body parts resulting from the same activity. Hand
      data from limited activities cannot, however, be used to conservatively predict
      loadings that might occur on other body surfaces without regard to activity since
      non-hand loadings attributable to higher contact activities exceeded hand
      loadings resulting from lower contact activities. Differences between pre- and
      post-activity loadings also demonstrate that dermal contact with soil is
      episodic. Typical background (pre-activity) geometric mean loadings appear to be
      on the order of 10(-2) mg/cm2 or less. Because exposures are activity dependent,
      quantification of dermal exposure to soil will remain inadequate until data
      describing relevant human behavior (type of activity, frequency, duration
      including interval before bathing, clothing worn, etc.) are generated.

PMID- 8868227
TI  - Bacterial biosynthesis of indole-3-acetic acid.
AB  - Production of the phytohormone indole-3-acetic acid (IAA) is widespread among
      bacteria that inhabit the rhizosphere of plants. Several different IAA
      biosynthesis pathways are used by these bacteria, with a single bacterial strain
      sometimes containing more than one pathway. The level of expression of IAA
      depends on the biosynthesis pathway; the location of the genes involved, either
      on chromosomal or plasmid DNA, and their regulatory sequences; and the presence
      of enzymes that can convert active, free IAA into an inactive, conjugated form.
      The role of bacterial IAA in the stimulation of plant growth and
      phytopathogenesis is considered.

PMID- 8868228
TI  - Isolation and characterization of soil microorganisms capable of utilizing the
      herbicide diclofop-methyl as a sole source of carbon and energy.
AB  - Six nonfermentative Gram-negative bacilli were isolated from Manitoban soils
      after enrichment with diclofopmethyl. Microscopic examination and physiological
      and biochemical tests have identified the organisms as Sphingomonas paucimobilis,
      Acinetobacter baumannii, Chryseomonas luteola, Pseudomonas aureofaciens,
      Pseudomonas cepacia, and Pseudomonas fluorescens. Growth curve studies showed
      that each of the isolates was able to grow in minimal medium with diclofop-methyl
      as the sole source of carbon and energy. Chemical analysis confirmed that all of
      the added diclofop-methyl (1.5 micrograms.mL-1) had been utilized after 31 h of
      incubation at 25 degrees C.

PMID- 8868229
TI  - Degradation of diclofop-methyl by pure cultures of bacteria isolated from
      Manitoban soils.
AB  - Pure cultures of Chryseomonas luteola and Sphingomonas paucimobilis isolated from
      Manitoban soils were able to utilize diclofop-methyl (methyl-2-[4-(2,4
      dichlorophenoxy)phenoxy] propanoate) as the sole source of carbon and energy. An
      actively growing culture of C. luteola completely degraded 1.5 micrograms
      diclofop-methyl.mL-1 to diclofop acid and 4-(2,4-dichlorophenoxy)phenol within 71
      h, as determined by gas chromatographic analysis. The accumulation of these
      metabolites in the growth medium resulted in the cessation of growth, indicating
      the organism's inability to degrade phenoxyphenol in the presence of diclofop
      acid. Sphingomonas paucimobilis mineralized 1.5 micrograms diclofop-methyl.mL-1
      to diclofop acid within 54 h. A biphasic growth pattern indicated that this
      organism was capable of degrading diclofop acid to 4-(2,4-dichlorophenoxy)phenol
      and 2,4-dichlorophenol and (or) phenol. Neither of the organisms was able to
      utilize 2,4-dichlorophenol as the sole source of carbon and energy.

PMID- 8868230
TI  - Modulation of carbohydrate-binding capacities and attachment ability of
      Bradyrhizobium sp. (lupinus) to white lupin roots.
AB  - The attachment of Bradyrhizobium sp. (Lupinus) strain MSDJ718 to excised roots of
      white lupin was examined. Maximal attachment occurred at early to middle log
      phases of bacterial growth. This binding was pH dependent, with an optimal value
      reached at 6.6. Irrespective of the culture age, the attachment was strongly
      affected by the calcium concentration of the growth medium: a Ca2+ limitation in
      the Bergersen medium led to optimal attachment of the bacteria. When L-fucose was
      added during the attachment assay, a significant inhibition was observed. The
      binding was stimulated when bacteria were cultivated with lupin root extracts,
      genistein and genistin (two lupin isoflavonoids), and some monosaccharides. In
      addition, with a spectrofluorimetric method using fluoresceinylated
      neoglycoproteins, it was shown that the increase of the attachment of bacteria to
      host cells was correlated to the increase of the L-fucoside binding capacity of
      the rhizobial cells. Taken together, the results obtained in the present study
      evidenced a possible role of the L-fucose specific bacterial lectin previously
      described in the Rhizobium-lupin host cell recognition.

PMID- 8868231
TI  - Physicochemical properties of PM-factor, a surface-active agent produced by
      Pseudomonas marginalis.
AB  - An extracellular surface-active agent, PM-factor, was obtained by high-speed
      centrifugation from the culture broth of Pseudomonas marginalis PD-14B. PM-factor
      exhibited emulsifying activity on a broad spectrum of hydrocarbon liquids,
      including aromatics, aliphatics, crude oil, and creosote. The factor appeared as
      ball-shaped particles of varying diameter when examined by electron microscopy
      (0.16-1.4 microns). Gel filtration chromatography demonstrated a high molecular
      mass of the factor (> 10(6) Da). The ultraviolet absorption spectrum manifested a
      peak in the region 200 nm rather in the region 260-280 nm. Amino acid analysis
      showed a very low amount of aromatic amino acids residues in the protein moiety
      of PM-factor. The presence of 3-deoxy-D-mannooctulosonic acid, heptose,
      hexosamine, phosphorus, and 3-hydroxy fatty acid indicated that PM-factor
      contained lipopolysaccharide. The emulsifying activity of PM-factor was inhibited
      strongly by mercuric chloride and moderately by EDTA. Polymyxin B, Ca2+, and Mg2+
      markedly stimulated the factors emulsifying activity. Roles of the bioemulsifier
      in the functioning of P. marginalis as a plant pathogen and in bioremediation are
      discussed.

PMID- 8868232
TI  - Selective enumeration of aromatic and aliphatic hydrocarbon degrading bacteria by
      a most-probable-number procedure.
AB  - A most-probable-number (MPN) procedure was developed to separately enumerate
      aliphatic and aromatic hydrocarbon degrading bacteria, because most of the
      currently available methods are unable to distinguish between these two groups.
      Separate 96-well microtiter plates are used to estimate the sizes of these two
      populations. The alkane-degrader MPN method uses hexadecane as the selective
      growth substrate and positive wells are detected by reduction of
      iodonitrotetrazolium violet, which is added after incubation for 2 weeks at 20
      degrees C. Polycyclic aromatic hydrocarbon degraders are grown on a mixture of
      phenanthrene, anthracene, fluorene, and dibenzothiophene in a second plate.
      Positive wells turn yellow to greenish-brown from accumulation of the partial
      oxidation products of the aromatic substrates and they can be scored after a 3
      week incubation period. These MPN procedures are accurate and selective. For pure
      cultures, heterotrophic plate counts on a nonselective medium and the appropriate
      MPN procedure provide similar estimates of the population density. Bacteria that
      cannot grow on the selective substrates do not produce false positive responses
      even when the inoculum density is very high. Thus, this method, which is simple
      enough for use in the field, provides reliable estimates for the density and
      composition of hydrocarbon-degrading microbial populations.

PMID- 8868233
TI  - Characterization of sulfate-reducing bacteria isolated from oil-field waters.
AB  - The occurrence and metabolic capacities of sulfate-reducing bacteria (SRB) were
      studied in 23 water samples taken from producing wells at 14 different sites. Oil
      fields in France, the North Sea, and the Gulf of Guinea were selected and
      classified according to physicochemical parameters (salinity ranging from 0.3 to
      120 g.L-1 and temperature between 29 and 85 degrees C). After the distribution of
      SRB within oil fields was studied, several strains of SRB were isolated and
      characterized metabolically. Twenty of the thirty-seven strains were not related
      to any known species. Most of the identified strains were members of the genera
      Desulfovibrio and Desulfotomaculum by molecular, morphological, and physiological
      properties.

PMID- 8868234
TI  - An endo-beta-1,4-glucanase gene (celA) from the rumen anaerobe Ruminococcus albus
      8: cloning, sequencing, and transcriptional analysis.
AB  - A genomic library of Ruminococcus albus 8 DNA was constructed in Escherichia coli
      using bacteriophage lambda ZapII. This library was screened for cellulase
      components and several Ostazin brilliant red/carboxymethyl cellulose positive
      clones were isolated. All of these clones contained a common 3.4-kb insert, which
      was recovered as a plasmid by helper phage excision. The carboxymethyl cellulase
      coding region was localized to a 1.4-kb region of DNA by nested deletions, and a
      clone containing the entire celA gene was sequenced. Analysis of the sequence
      revealed a 1231-bp open reading frame, coding for a protein of 411 amino acids
      with a predicted molecular weight of 45 747. This protein, designated CelA,
      showed extensive homology with family 5 endoglucanases by both primary amino acid
      sequence alignment and hydrophobic cluster analysis. Cell-free extracts of E.
      coli containing the celA clone demonstrated activity against carboxymethyl
      cellulose and acid swollen cellulose but not against any of the p-nitrophenol
      glycosides tested, indicating an endo-beta-1,4-glucanase type of activity. In
      vitro transcription-translation experiments showed that three proteins of 48,000,
      44,000, and 23,000 molecular weight were produced by clones containing the celA
      gene. Northern analysis of RNA extracted from R. albus 8 grown on cellulose
      indicated a celA transcript of approximately 2700 bases, whereas when R. albus 8
      was grown on cellobiose, celA transcripts of approximately 3000 and 600 bases
      were detected. Primer extension analysis of these RNAs revealed different
      transcription initiation sites for the celA gene when cells were grown with
      cellulose or cellobiose as the carbon source. These two sites differed by 370
      bases in distance. A model, based on transcription and sequence data, is proposed
      for celA regulation.

PMID- 8868235
TI  - Rhizobium leguminosarum as a plant growth-promoting rhizobacterium: direct growth
      promotion of canola and lettuce.
AB  - Early seedling root growth of the nonlegumes canola (Brassica campestris cv.
      Tobin, Brassica napus cv. Westar) and lettuce (Lactuca sativa cv. Grand Rapids)
      was significantly promoted by inoculation of seeds with certain strains of
      Rhizobium leguminosarum, including nitrogen- and nonnitrogen-fixing derivatives
      under gnotobiotic conditions. The growth-promotive effect appears to be direct,
      with possible involvement of the plant growth regulators indole-3-acetic acid and
      cytokinin. Auxotrophic Rhizobium mutants requiring tryptophan or adenosine
      (precursors for indole-3-acetic acid and demonstrate a new facet of the Rhizobium
      plant relationship and that Rhizobium leguminosarum can be considered a plant
      growth-promoting rhizobacterium (PGPR).

PMID- 8868236
TI  - Isolation and characterization of a gene encoding a chymotrypsin-like serine
      protease from Streptomyces lividans 66.
AB  - A gene encoding a Streptomyces lividans homologue of the chymotrypsin-like serine
      protease (SAM-P20) of Streptomyces albogriseolus was isolated using the
      Streptomyces griseus prtB gene as a hybridization probe. Nucleotide sequence
      analysis of a representative clone uncovered the possible presence of a sequence
      of 900 nucleotides encoding 300 amino acids, including a putative "prepro" region
      of 115 amino acids. Alignment of the predicted amino acid sequence of this
      putative gene with other members of the family of Streptomyces extracellular
      chymotrypsin-like proteases indicated a high degree of homology in all cases,
      especially with the SAM-P20 protease. This gene product has been identified as
      the second member of a potentially larger family of SAL (SAM-P20-like) proteases
      in S. lividans 66.

PMID- 8868237
TI  - Growth of rhodococcus S1 on anthracene.
AB  - Three slow-growing bacteria were isolated from a mixed culture enriched for
      growth on anthracene, using creosote-contaminated soil as the inoculum. Organisms
      were shown to use anthracene by the production of a clear zone around the colony
      after a mineral salts agar plate was sprayed with anthracene. All three bacteria
      were nonmotile, nonsporulating, gram-positive rods and stained acid-fast.
      Physiological and biochemical tests, GC content, and cell wall lipid patterns of
      whole cell methanolysates indicated that they belonged to the Nocardia
      Mycobacterium-Rhodococcus group. On the basis of these characteristics and
      pyrolysis gas chromatography, they were assigned to the genus Rhodococcus. Growth
      of the isolates was slow on crystalline anthracene, giving a doubling time of 1.5
      3 days, and they grew mainly on the crystal surface. When anthracene was supplied
      by precipitation from a solvent, doubling time was reduced to 1 day. All three
      isolates mineralized anthracene but not phenanthrene or naphthalene, nor could
      they grow on naphthalene, phenanthrene, fluorene, fluoranthene, acenaphthene,
      pyrene, chrysene, or naphthacene as sole carbon source. One isolate, Rhodococcus
      S1, was able to use 2-methylanthracene or 2-chloroanthracene as carbon source but
      not 1- or 9-substituted analogs. These results suggest that the initial enzyme
      attacking anthracene in these isolates has a narrow substrate specificity.

PMID- 8868238
TI  - Purification and properties of aromatic amino acid aminotransferases from
      Azospirillum brasilense UAP 14 strain.
AB  - The purification and characterization of AAT1, one of two aromatic amino acid
      aminotransferase (EC 2.6.1.57) in Azospirillum brasilense, is described. Purified
      AAT1 had a subunit mass of 33 kDa and a nondenatured molecular mass of 66 kDa,
      suggesting a dimeric structure. Other properties include a pI of 5.04, an optimum
      temperature of 45 degrees C, and optimum pH of 8.5. AAT1 utilized all aromatic
      amino acids, the L-tryptophan derivatives such as L-5-methyl tryptophan and L
      flour-tryptophan, and L-histidine. The apparent Km values for L-tyrosine, L
      phenylalanine, and L-tryptophan were 0.19, 0.43, and 1.05 mM, respectively. The
      enzyme was competive inhibited by indole-3-pyruvic acid with a Ki of 0.17 mM.

PMID- 8868239
TI  - A comparative study on the conditions of growth and sporulation of three strains
      of Clostridium perfringens type A.
AB  - Different conditions of growth and sporulation of a strain of Clostridium
      perfringens type A (NCTC 8798) and two derived mutant strains, the lysozyme
      germination dependent strain 8-6 and the revertant strain R3, have been
      determined. No sporulation was detected for the three strains in the Duncan and
      Strong (DS) medium; 100% sporulation was routinely obtained for the two mutant
      strains in the defined (D) medium. Factors promoting in vitro sporulation of C.
      perfringens type A were assayed: the volume of the culture, the type of
      preculture, and the addition of lysozyme in precultures. The paper also provided
      additional information on growth and sporulation of the mutant strains 8-6 and
      R3. Glucose concentrations up to 11 mM produced high percentages of sporulation.
      However, strain R3 still sporulated at 20% with 56 mM of glucose. A high volume
      of D medium led to slow growth kinetics and favoured sporulation. Faster kinetics
      of growth and the best percentage of sporulation were obtained with a young
      inoculum of the two mutant strains. On the other hand, the type of medium in the
      precculture (fluid thioglycollate (FTG) or basal carbonate yeast trypticase
      (BCYT)) did not influence the percentage of sporulation. However, while strain R3
      was not affected by the addition of lysozyme in D medium, kinetics of growth were
      strongly influenced by this addition in strain 8-6, and the percentage of
      sporulation increased with a preculture in FTG medium and decreased when BCYT
      medium was used.

PMID- 8868240
TI  - Differential expression of ornithine decarboxylase, poly(ADP)ribose polymerase,
      and mitochondrial mRNAs following testosterone administration to
      hypophysectomized rats.
AB  - The mRNAs of the nuclear encoded genes, ornithine decarboxylase (ODCase) and
      poly(ADP)ribose polymerase (PADPRP), and the mitochondrial encoded genes,
      cytochrome oxidase I and II (COI and COII) and ATPase 6, are differentially
      expressed during spermatogenesis (Alcivar et al., 1989: Biol Reprod 41:1133;
      1989: Dev Biol 135:263; 1991: Biol Reprod 46:201). In this study, we use Northern
      blotting to examine the steady state levels of ODCase, PADPRP, COI, COII, and
      ATPase 6 mRNAs in testes of hypophysectomized male rats following testosterone
      administration. Four weeks after hypophysectomy, rats received 24 cm subcutaneous
      implants of testosterone-filled polydimethylsiloxane (PDS) and were killed at 3,
      7, 14, 28, and 56 days thereafter. After hypophysectomy, the steady state levels
      for the PADPRP, COI, COII, and ATPase 6 mRNAs were not significantly different
      from controls, although hypophysectomy caused a 44% loss of preleptotene
      spermatocytes and an 88% loss of pachytene spermatocytes, the testicular cell
      types expressing the highest levels of these mRNAs. In contrast, the levels of
      the two ODCase mRNAs were greatly decreased after hypophysectomy and mirrored the
      number of germinal cells present in the testis. After testosterone treatment,
      ODCase mRNA levels remained low 3 days after treatment and gradually increased at
      days 14, 28, and 56. No major hybridization signal changes in PADPRP, COI, COII,
      and ATPase mRNA were observed after testosterone treatment. We conclude that the
      steady state mRNA levels for the housekeeping ODCase gene respond differently
      after hypophysectomy and testosterone treatment of male rats than the PADPRP and
      mitochondrial DNA transcripts.

PMID- 8868241
TI  - Promoter mapping of the mouse Tcp-10bt gene in transgenic mice identifies
      essential male germ cell regulatory sequences.
AB  - Transgenic mice were generated to localize essential promoter elements in the
      mouse testis-expressed Tcp-10 genes. These genes are expressed exclusively in
      male germ cells, and exhibit a diffuse range of transcriptional start sites,
      possibly due to the absence of a TATA box. A series of transgene constructs
      containing different amounts of 5' flanking DNA revealed that all sequences
      necessary for appropriate temporal and tissue-specific transcription of Tcp-10
      reside between positions -1 to -973. All transgenic animals containing these
      sequences expressed a chimeric transgene at high levels, in a pattern that
      paralleled the endogenous genes. These experiments further defined a 227 bp
      fragment from -746 to -973 that was absolutely essential for expression. In a gel
      shift assay, this 227-bp fragment bound nuclear protein from testis, but not
      other tissues, to yield two retarded bands. Sequence analysis of this fragment
      revealed a half-site for the AP-2 transcription factor recognition sequence. Gel
      shift assays using native or mutant oligonucleotides demonstrated that the
      putative AP-2 recognition sequence was essential for generating the retarded
      bands. Since the binding activity is testis-specific, but AP-2 expression is not
      exclusive to male germ cells, it is possible that transcription of Tcp-10
      requires interaction between AP-2 and a germ cell-specific transcription factor.

PMID- 8868242
TI  - Persistence of the developmental block of in vitro fertilized domestic cat
      embryos to temporal variations in culture conditions.
AB  - A series of studies examined the influence and temporal interaction of energy
      substrate, media complexity, and tissue co-culture on the development of in vitro
      fertilized cat embryos and the persistence of the morula-to-blastocyst
      developmental block. In study I, oocytes were fertilized and cultured for 144 hr
      in a simple culture medium (modified Krebs Ringer bicarbonate; mKrb), containing
      either glucose or glutamine, or cultured in mKrb w/ glutamine for the initial 72
      hr with transfer to mKrb w/ glucose for the final 72 hr. Fertilization rate,
      percent development to morulae, and cell number per embryo were similar (P >
      0.05) between treatments and blastocyst formation was universally low (< 10%). In
      Study II, oocytes were fertilized and cultured in either mKrb (w/glucose or
      glutamine) or in a complex medium, Ham's F10 (w/ 10% fetal bovine serum [FBS]).
      After 72 hr of initial culture, embryos in mKrb were transferred into Ham's F10.
      Fertilization rate was lower (P < 0.01) in Ham's F10 but embryo development to
      the morulae stage and cell number per embryo were comparable (P > 0.05) for all
      treatments. A higher percentage of blastocysts and morulae becoming blastocysts
      were observed after initial culture in mKrb w/ glutamine than after initial
      culture in mKrb w/ glucose. In Study III, oocytes were fertilized and cultured
      initially in mKrb (w/ glutamine), and then switched to either Ham's F10 or cat
      oviductal cell monolayers (in Ham's F10). Additional embryos were cultured
      exclusively in Ham's F10 or on cat oviductal cell monolayers. Fertilization rates
      were lower (P < 0.05) on oviductal cells but cell number per embryo was similar
      (P > 0.05) in all treatments. Blastocyst formation was lower (P < 0.05) on
      oviductal cells than in mKrb-Ham's F10 treatment and was < 20% in all treatments.
      In summary, while in vitro fertilization-derived cat embryos develop to morulae
      under a variety of culture conditions, the morula-to-blastocyst developmental
      block was minimally responsive to alterations in energy substrate and medium
      complexity or fluctuations in their temporal availability. In addition, oviductal
      cell culture, alone or in combination with other culture variations, was
      ineffective in overcoming the developmental block.

PMID- 8868243
TI  - Electrofusion parameters for nuclear transfer predicted using isofusion contours
      produced with bovine embryonic cells.
AB  - Electrofusion is a valuable technique for the nuclear transfer procedure. An
      enucleated oocyte is electrofused with a blastomere to create a nuclear transfer
      embryo. The present study constructed isofusion contours after the electrofusion
      of identical coupled cells that characterized all the bovine embryonic cell types
      used in nuclear transfer. The intersection of isofusion contours for enucleated
      oocytes and blastomeres provided the parameters for electrofusion during nuclear
      transfer. Blastomeres isolated from in vitro produced embryos 3-6 days after (in
      vitro fertilization) were electrofused with oocytes enucleated by centrifugation
      (85, 87, 89, and 73% electrofusion, respectively). The cleavage (46, 40, 37, and
      28%, respectively) of the nuclear transfer embryos produced a trend that
      decreased as the age of the blastomeres increased. The isofusion contours
      provided information about the interaction between different cell types in an
      electric field, and gave precise electrofusion parameters for a range of bovine
      embryonic cell types used in nuclear transfer.

PMID- 8868244
TI  - Metabolism and cell allocation during parthenogenetic preimplantation mouse
      development.
AB  - Diploid parthenogenetic postimplantation mouse embryos, containing two maternal
      genomes, are characterized by poor development of extraembryonic membranes
      derived from the trophectoderm and primitive endoderm of the blastocyst. This is
      thought to be caused by a deficiency of expression of paternally derived
      imprinted genes. Here we have compared the inner cell mass, from which the
      primitive endoderm and fetal lineages are derived, and the trophectoderm, which
      forms a major component of the placenta, in parthenogenetic and fertilized
      preimplantation embryos. We have also studied the metabolism from the 1-cell to
      the blastocyst stage. Cell numbers were reduced in the ICM and TE of
      parthenogenetic blastocysts compared to fertilized blastocysts. This was thought
      to be due to the increased levels of cell death observed in these lineages.
      Pyruvate and glucose uptake by parthenogenetic embryos was similar to that by
      fertilized embryos throughout preimplantation development. However, at the
      expanded blastocyst stage glucose uptake by parthenogenetic embryos was
      significantly higher than by fertilized embryos. The implications of the actions
      of imprinted genes and of X-inactivation is discussed.

PMID- 8868245
TI  - Effects of metabolic inhibitors on mouse preimplantation embryo development and
      the energy metabolism of isolated inner cell masses.
AB  - The effects of two metabolic inhibitors, methyl palmoxirate (MP) and amino
      oxyacetate (AOA), on mouse preimplantation embryo development and cell number,
      and inner cell mass. (ICM) cell metabolism have been examined. Two-cell embryos
      were cultured in media supplemented with either MP, which inhibits fatty acid
      oxidation, or AOA, which inhibits the transamination of glutamate into alpha
      ketoglutarate. Embryos were scored for development daily. On day 5, expanded
      blastocysts were differentially labeled with fluorochromes to visualize TE and
      ICM cell nuclei, or the ICMs isolated by immunosurgery and their energy
      metabolism determined using microfluorometric methods. Embryos exposed to the two
      inhibitors developed into fully expanded blastocysts, although cell numbers of
      both the TE and ICM cells were significantly reduced compared to controls. The
      uptake of glucose in the presence of 1 mM MP or AOA did not differ from the
      controls, but less glucose was accountable for by lactate production. MP
      significantly reduced lactate production. In the presence of 4 mM AOA, the amount
      of glucose oxidized and the amount of lactate formed by ICMs were significantly
      reduced. The results indicate that the fuels used by isolated mouse ICMs vary in
      response to substrate availability and that fatty acids may be a potential energy
      source.

PMID- 8868246
TI  - Influence of "Solcoseryl" during culture on the sex-dependent repair of bovine
      demi-embryos.
AB  - The purpose of this experiment was to determine the effect of culture conditions
      on the development of split embryos after bisection and on the sex ratio of
      resultant bovine demi-embryos. Embryos that had developed into blastocysts on
      days 6 1/2 to 7 or on days 7 1/2 to 8 from oocytes matured and fertilized in
      vitro were bisected in BMOC-3 medium supplemented with 33% calf serum. The medium
      also contained 0%, 0.1% or 1.0% Solcoseryl, a deproteinized hemodialysate product
      from calf blood. The demi-embryos were first cultured for 4 hours in the same
      medium in which they had been bisected and then co-cultured with cumulus cells in
      TCM199 supplemented with 1% calf serum for an additional 20 hr. The rate of
      production of good to excellent quality demi-embryos obtained from days 6 1/2 to
      7 blastocysts was higher than from those on days 7 1/2 to 8. The rate was also
      significantly improved when blastocysts were bisected in medium containing 0.1%
      or 1.0% Solcoseryl, compared to the medium without Solcoseryl. Male embryos
      seemed to recover more rapidly than female embryos, as assessed by morphological
      quality at 4 hr, although the quality of female embryos had improved by 24 hr.
      The percentage of males after culture was higher in the medium without Solcoseryl
      than in its presence. Thus, addition of Solcoseryl at either 0.1% or 1.0% to BMOC
      3 medium seemed to improve the production efficiency of good quality demi
      embryos, but did not influence the sex ratio. It appears as if female demi
      embryos required more time than male embryos to be repaired after bisection.

PMID- 8868247
TI  - Influence of genetic background and media components on the development of mouse
      embryos in vitro.
AB  - One-cell embryos from some inbred and random-bred mice, but not those derived
      from certain F1 hybrids, suffer from a block during in vitro development known as
      the two-cell block. This two-cell block can be overcome by removing glucose or
      inorganic phosphate from the culture system or by altering the ratio of other
      medium components such as sodium, potassium, or bicarbonate. This issue is made
      more complex by the fact that the rate of development is different for each
      strain of mouse and this rate of development is invariably slowed under in vitro
      culture conditions. This study investigated the role of glucose and inorganic
      phosphate, individually or in combination, in relation to the two-cell block, and
      rate of development in vitro of two random-bred strains (CF-1 and CD-1) and an F2
      hybrid derived from a nonblocking F1 hybrid cross (C57Bl/6NCr x C3H/HeNCr).
      Results were compared with in vivo data for each strain, and between media. There
      was a significant difference in the rate of preimplantation development in vivo
      of the three strains chosen, which was mirrored in vitro, regardless of the
      medium. The two random-bred strains suffered from a glucose-related two-cell
      block which was primarily mediated by inorganic phosphate. Inorganic phosphate
      was detrimental to embryo development regardless of strain or the presence of
      glucose. Although glucose, in the absence of inorganic phosphate, resulted in
      some blocking in development in the inbred strains initially, its presence in
      media was associated with increased rates of development at later stages in
      embryos that did not block. Glucose, but not inorganic phosphate, was beneficial
      but not essential to the development of the F2 embryos. The results of this study
      demonstrated that mouse embryos from different strains have differential rates of
      development in vivo and in vitro, and different sensitivities to glucose and
      inorganic phosphate. The two-cell block was primarily induced in the combined
      presence of glucose and inorganic phosphate. Glucose was beneficial in the
      absence of inorganic phosphate, and inorganic phosphate was detrimental to the
      rate of in vitro development.

PMID- 8868248
TI  - Identification of the rat epididymis-secreted 4E9 antigen as protein E: further
      biochemical characterization of the highly homologous epididymal secretory
      proteins D and E.
AB  - Epididymis-secreted proteins D and E have been purified to homogeneity and
      partially characterized, and it is shown that monoclonal antibody (MAb) 4E9
      (raised against a detergent extract of rat caudal epididymal sperm [Moore et al.,
      1994: Mol Reprod Dev 37(2):181-194]) recognizes protein E, but not protein D. The
      molecular weight of protein D (approximately 30 kD) is approximately 2 kD lower
      than protein E (approximately 32 kD). The NH2-terminus of each protein is
      blocked; however, microsequencing of internal peptides confirms earlier reports
      of significant sequence identity between the two proteins. High performance
      liquid chromatography tryptic peptide mapping showed peak differences between the
      two proteins, but it was not possible to obtain amino acid sequence in the peaks
      that were different. The epitope for MAb 4E9 was localized in the blocked NH2
      terminus-CNBr peptide derived from protein E. The epitope was destroyed by
      protease treatment of protein E. Removal of N-linked oligosaccharides did not
      destroy the epitope for MAb 4E9 and did not affect the molecular weight
      difference between the proteins.

PMID- 8868249
TI  - Comparative immunogold analysis of tubulin isoforms in the mouse sperm flagellum:
      unique distribution of glutamylated tubulin.
AB  - The distribution of different tubulin isoforms in the mouse sperm flagellum was
      studied using four site-directed antibodies to tubulin: DM1A and DM1B general
      anti alpha and beta-tubulin, 6-11B-1 anti-acetylated alpha-tubulin, and GT335
      anti-glutamylated alpha and beta-tubulin. Quantitative immunogold analyses were
      performed on five regions of the flagellum: the middle piece, three successive
      regions of the principal piece, and the terminal piece. A uniform labeling was
      observed with DM1A and DM1B along the entire flagellum both for peripheral
      doublets and the central pair. Similar results were obtained with 6-11B-1
      directed to acetylated alpha-tubulin, an N-terminal-modified tubulin isoform. In
      contrast, the labeling for glutamylated alpha and beta-tubulin, C-terminal
      modified isoforms, was not uniform. The highest intensity was found in the middle
      piece and the terminal piece. The labeling which decreased significantly both for
      peripheral doublets and central pair along the principal piece was considered as
      a loss of glutamylated tubulin accessibility. From the middle piece to the end of
      the principal piece, this labeling was predominant in doublets 1-5-6,
      corresponding to the plane of the flagellar wave. However, the labeling for
      doublets 2-3-4-7-8-9 was heterogeneous, showing an increasing asymmetry. These
      results suggest that in the mammalian sperm cell model, the glutamylated tubulin
      might be involved in a functional heterogeneity among peripheral doublets of the
      flagellum.

PMID- 8868250
TI  - Sperm protein (sp50) binds to acrosome and plasma membranes in a Ca(2+)-dependent
      manner: possible role in acrosome reaction.
AB  - Annexins are a family of Ca(2+)-binding proteins involved in the exocytotic
      process. The presence and the role of annexins in mammalian spermatozoa have not
      been well established. Two annexin-like proteins were obtained from guinea pig
      testis, a doublet of Mr 31-33 kD (p31/33) and a protein of Mr 50 kD (p50). Both
      proteins were able to bind to erythrocyte ghosts in a Ca(2+)-dependent fashion.
      Polyclonal antibodies against p31/33 reacted with two major proteins, Mrs 50 kD
      (sp50) and 42 kD (sp42), from mature and immature guinea pig spermatozoa. p50 and
      sp50 are likely the native proteins from testis and spermatozoa, respectively,
      and they are seemingly related. By immunofluorescence, sp50 was only found in the
      acrosome region of immature and capacitated and noncapacitated spermatozoa, and
      its location was intracellular. In spermatozoa undergoing acrosome reaction, sp50
      was detected in the whole acrosome, while in spermatozoa that had undergone
      acrosome reaction sp50 was not detected. However, in the protein pattern of
      acrosome reaction vesicles, anti-p31/33 antibody revealed diffuse bands of Mr 35
      38 kD. sp50 was able to bind to plasma membrane fragments and acrosome outer
      membrane from demembranated sperm in a Ca(2+)-dependent fashion. The presence of
      sp50 in the acrosome region, its distribution throughout the acrosome membrane
      just before the acrosome reaction, and its ability to bind both plasma and outer
      acrosome membranes in a Ca(2+)-dependent manner suggest that sp50 may participate
      in the acrosome reaction mechanism in guinea pig spermatozoa.

PMID- 8868251
TI  - Development-dependent localization of nuclear antigens in growing mouse oocytes.
AB  - We have analyzed the distribution of nuclear and nucleolar proteins during the
      period of oocyte's growth. Oocytes were isolated mechanically or enzymatically
      from ovaries of juvenile mice of various ages (from 1 to 28 days after birth).
      Small nuclear ribonucleoproteins (snRNPs), the splicing factor SC-35, and a
      protein linked to cell proliferation (p-120) were detected by indirect
      immunofluorescence. snRNP distribution is consistent with the prophase state of
      oocyte's nuclei, while SC-35 (and p-120) exhibit a "speckled" distribution
      throughout the entire period of growth. The number of speckles (or foci) appears
      maximal around 10 days after birth, i.e., in the period of maximal
      transcriptional activity, and is sensitive to alpha-amanitin treatment. On the
      other hand, the immunofluorescent distribution of of nucleolin and p-103 (a
      nucleolar marker of the granular component) is compared to the ultrastructural
      distribution of the granular component analyzed by electron microscopy on oocytes
      of the same age.

PMID- 8868252
TI  - Propranolol induces polyspermy during sea urchin fertilization.
AB  - Propranolol, a beta-adrenergic receptor blocker, is found to induce polyspermy in
      sea urchin eggs. Unfertilized sea urchin eggs treated for 10 min with 50 microM
      of propranolol, and then inseminated, become polyspermic and show a fertilization
      envelope which is barely visible to the light microscope. Examination of treated
      eggs by transmission and scanning electron microscopy shows that the drug does
      not alter the cortex of the unfertilized egg. However, after insemination an
      incomplete cortical reaction occurs. This might well account for both polyspermy
      and the defective elevation of the fertilization envelope. Since the effects of
      the drug are reversed by simultaneous treatment with adrenalin, perhaps
      propranolol interferes with the monoaminergic system that has been proposed to be
      active. The involvement of the monoaminergic system in the fertilization process
      is present in the sea urchin egg.

PMID- 8868253
TI  - Heterogeneous distribution of fibronectin, tenascin-C, and laminin immunoreactive
      material in the cumulus-corona cells surrounding mature human oocytes from IVF-ET
      protocols--evidence that they are composed of different subpopulations: an
      immunohistochemical study using scanning confocal laser and fluorescence
      microscopy.
AB  - Monoclonal antibodies and immunofluorescence microscopy, including laser confocal
      microscopy, were used in this study to point out the production of fibronectin,
      tenascin-c, and laminin in the cumulus-corona (CC) cells surrounding mature human
      oocytes from IVF-ET protocols in view of their presumptive importance in the
      coordination of the processes leading to fertilization and early embryo cleavage,
      including the final maturation of the ovum, the sperm-egg interaction, and the
      "complex biochemical dialogue" between the gamete and the oviduct through the
      tubal luminal environment. One hundred fifty mature oocyte-CC complexes were
      obtained from IVF-ET protocols and fixed in 4.0% buffered paraformaldehyde.
      Specimens were incubated with a panel of primary monoclonal antibodies (mabs)
      recognizing different epitopes of fibronectin, tenascin-c, and laminin and then
      with fluorescein isothiocyanate-conjugated goat anti-mouse IgG. Observations were
      made by a scanning confocal microscope (Sarastro 2000) and a photomicroscope
      (Polyvar, Reichert-Jung) equipped with epifluorescence optics. The
      immunohistochemical data demonstrated that human CC cells are capable of
      producing fibronectin and tenascin-c but that their production is not homogeneous
      in the CC population. In fact, fibronectin immunoreactivity was shown mostly by
      inner CC cells (mainly corona cells), whereas tenascin was produced by some cells
      scattered in the entire cumulus mass. Moreover, fibronectin and tenascin-c
      immunoreactive material was observed in the intracytoplasmic areas, at the plasma
      membrane level as well as in the extracellular matrix. On the contrary, laminin
      immunofluorescent material was found around plasma membranes of almost all CC
      cells, but a clear intracytoplasmic reaction was never observed. This leads us to
      assume that laminin in the extracellular matrix remains entrapped once produced
      by granulosa follicular cells and that in the postovulatory period no active
      secretion occurs in CC cells. Even though the functional role of these
      extracellular matrix proteins remains still unclear, it is reasonable to suggest
      that they are necessary in various steps of the reproductive process, i.e., from
      the pick-up of the oocyte, its transport through the oviduct, and fertilization,
      up until the early cleavage of the embryo. Finally, functional differences
      between "corona radiata" and "cumulus" cells during the oocyte denudation may be
      accounted for particular distribution of these adhesive proteins.

PMID- 8868254
TI  - Adenosine inhibits L- and N-type calcium channels in pituitary melanotrophs.
      Evidence for the involvement of a G protein in calcium channel gating.
AB  - It has been previously demonstrated that activation of A1 adenosine receptors in
      frog melanotrophs causes inhibition of spontaneous action potential discharges
      and alpha-melanocyte-stimulating hormone secretion. In the present study, we have
      investigated the effect of adenosine on high-voltage-activated (HVA) calcium
      currents in cultured melanotrophs, using the whole-cell variant of the patch
      clamp technique with barium as a charge carrier. Adenosine and the specific A1
      adenosine receptor agonist R-PIA (50 microM each) produced a decrease of the
      amplitude of the barium current, while the selective A2 adenosine receptor
      agonist CGS 21680 did not affect the current. The inhibitory effect of R-PIA was
      observed throughout the activation range of the current, with stronger responses
      at more positive potentials. R-PIA inhibited both the L- and N-type components of
      the current, the effect on the N-component being two-fold higher than on the L
      component. The inhibitory effect of R-PIA was rendered irreversible by addition
      of GTP gamma S (100 microM) to the intracellular solution. Pre-treatment of the
      cells with pertussis toxin (1 microgram/ml; 12 h) totally abolished the effect of
      R-PIA on the HVA calcium channels. Conversely, addition of a high concentration
      of cAMP (100 microM) together with the phosphodiesterase inhibitor IBMX (100
      microM) to the intracellular solution did not modify the effect of R-PIA on the
      current. It is concluded that, in frog melanotrophs, adenosine induces inhibition
      of L- and N-calcium currents and that this effect is mediated by a pertussis
      toxin-sensitive G protein. Our data also indicate that the inhibitory effect of
      adenosine on the calcium currents is not mediated by inhibition of adenylyl
      cyclase.

PMID- 8868256
TI  - Evidence for a trophic action of the glycoprotein hormone alpha-subunit in rat
      pituitary.
AB  - The effect of the alpha-subunit of luteinizing hormone (LH alpha) on lactotroph
      growth in 14-day-old rat pituitary was studied in vitro using a reaggregate
      pituitary cell culture system. LH alpha significantly expanded both the total
      population of cells expressing prolactin mRNA and the number of [3H]thymidine
      incorporating prolactin mRNA expressing cells. No such effect could be elicited
      by LH. Both effects were inhibited by simultaneous addition of an anti-LH alpha
      antiserum but not by normal rabbit serum. Anti-LH alpha antiserum added alone to
      the cultures caused a small decrease in the number of prolactin mRNA expressing
      cells and in [3H]thymidine labelling of the latter. It is concluded that LH alpha
      may be a trophic factor of lactotrophs not only during fetal development, as
      suggested by others previously, but also during the rapid expansion of this cell
      type during postnatal life in the rat.

PMID- 8868255
TI  - Morphine-induced locomotor and neurochemical stimulation is enhanced in
      transgenic mice with impaired glucocorticoid receptor function.
AB  - It has been suggested that the hypothalamic-pituitary-adrenocortical (HPA) system
      contributes to individual differences in sensitivity towards drug abuse.
      Therefore, we studied the effects of the prototypic drug morphine in transgenic
      mice with impaired glucocorticoid receptor function. This mouse model has a
      profoundly dysfunctional HPA feedback. Since morphine-induced locomotor
      stimulation is positively correlated with the rewarding effects of morphine, we
      examined morphine-induced locomotor activity of transgenic mice and control mice
      (B6C3F1). Because morphine-induced locomotor activity depends on an intact
      mesolimbic system, dopaminergic (DAergic) neuronal activity was also estimated
      within the mesolimbic system. Results indicated that the activity after vehicle
      injection do not differ between these two mouse lines. Compared to vehicle
      injections, morphine (7.5 and 15 mg/kg; i.p.) dose-dependently increased motor
      activity for 3 h in control and transgenic mice. However, morphine-induced
      locomotion was significantly more pronounced in transgenic mice. Further,
      morphine-induced mesolimbic DAergic activity was enhanced in transgenic animals
      as compared to control animals. These results parallel endocrine data that show
      that the plasma ACTH level of transgenic mice reach higher levels compared to
      those levels observed in control mice after morphine injections. Altogether, this
      transgenic mouse line shows an enhanced locomotor-stimulant effect to morphine, a
      response that is reflected by an enhanced DAergic activity within the mesolimbic
      system and is also associated with increased HPA activity. We submit that the
      dysregulation of the HPA system in these transgenic mice influences the enhanced
      vulnerability to drug-seeking behavior.

PMID- 8868257
TI  - Neural regulation of corticotropin releasing hormone (CRH) and CRH receptor mRNA
      in the hypothalamic paraventricular nucleus in the rat.
AB  - The role of afferent innervation to the hypothalamic paraventricular nucleus
      (PVN) on CRH mRNA and CRH receptor mRNA levels was studied in control and
      stressed rats. Groups of rats were subjected to unilateral transection of the
      stria terminalis (ST), the medial forebrain bundle at the rostral hypothalamic
      level (RMFB), or the lower brainstem through the medulla oblongata between the
      obex and the locus coeruleus (CBs). Twelve days after surgery, each group of rats
      was further divided into controls (basal conditions) and stressed (1 h
      immobilization), before collecting brains for mRNA analysis by in situ
      hybridization histochemistry. While ST and RMFB cuts had no effect on basal CRH
      mRNA levels in the PVN, CBs cut decreased CRH mRNA in the PVN ipsilaterally to
      the knife cut but it was without effect on the contralateral side (-40% and -37%
      vs contralateral and sham-operated, respectively, P < 0.01). Acute stress (rats
      were killed 3 h after immobilization) increased CRH mRNA levels by about 30%
      bilaterally, an effect which was unchanged by any of the three hemisections.
      Under basal conditions, CRH receptor mRNA levels in the PVN were
      indistinguishable from the surrounding areas in sham-operated controls, ST and
      RMFB operated rats. However, brainstem hemisection resulted in clear expression
      of CRH receptor mRNA in areas consistent with the dorsal, medial-ventral and
      lateral parvicellular subdivisions of the PVN, ipsilateral to the transection.
      CRH neurons in these subdivisions project to the lower brainstem and the spinal
      cord. Expression of CRH receptor mRNA in the medial-dorsal and anterior
      parvicellular divisions (CRH neurons with median eminence projections) was not
      affected by CBs cut. In these subdivisions, immobilization stress markedly
      increased CRH receptor mRNA levels but it did not influence CBs cut-induced CRH
      receptor expression. ST and RMFB hemisections were without effect on PVN CRH
      receptor mRNA levels under basal or stress conditions. Oxytocin (OT) and
      vasopressin (VP) mRNA levels in the magnocellular subdivision of the PVN were
      unchanged after immobilization, or following ST, RMFB or CBs cuts, whereas OT
      mRNA in the medial-ventral and caudal parvicellular subdivisions was decreased by
      52% after CBs cut. The data demonstrate that: 1) basal CRH mRNA levels in the PVN
      are under tonic stimulatory influence of the lower brainstem (and/or spinal cord)
      afferents; 2) CRH receptor mRNA expression in PVN subdivisions (pituitary vs
      lower brainstem/spinal cord projecting neurons) is under different control
      mechanisms, and 3) immobilization-induced changes in CRH mRNA and CRH receptor
      mRNA levels are mediated either by neural inputs from brain areas other than
      those investigated here, or by humoral factors.

PMID- 8868258
TI  - Influence of testosterone on LHRH release, LHRH mRNA and proopiomelanocortin mRNA
      in male sheep.
AB  - The mechanism whereby testosterone (T) reduces pulsatile LHRH and LH release is
      unknown. We tested the hypothesis that hypothalamic levels of LHRH mRNA decrease
      and proopiomelanocortin (POMC) mRNA increase coincident with reduced LHRH release
      induced by either long-term or short-term T treatment in male sheep. Experiment 1
      examined the effect of long-term T exposure on LHRH and LH release and LHRH and
      POMC mRNA levels. Yearling Suffolk rams were castrated and assigned to one of
      four treatments: 1) castrated (n = 4); 2) castrated, portal cannula (n = 5); 3)
      castrated+T (n = 4) and 4) castrated+T, portal cannula (n = 4). T-treated males
      received ten 10-cm silastic T-implants immediately after castration. Surgical
      placement of devices for collecting hypophyseal-portal blood occurred 2 to 3
      months after castration. Seven to 10 days after surgery, blood samples were
      collected at 10-min intervals for 8 h from portal cannulated males or for 5 h
      from non-cannulated males to assess pulsatile LHRH and/or LH release. Immediately
      after blood sample collection, hypothalamic tissue was collected for in situ
      measurement of LHRH or POMC mRNA. T-treatment decreased (P < 0.01) mean LHRH and
      LH and decreased (P < 0.01) LHRH and LH pulse frequency. T did not significantly
      affect (P > 0.10) silver grain area per LHRH neuron, but decreased (P < 0.01)
      silver grain area per POMC neuron. Portal cannulation tended to decrease (P =
      0.057) silver grain area per LHRH neuron without significantly affecting (P >
      0.10) LHRH cell numbers while reducing (P < 0.01) silver grain area per POMC
      neuron and POMC cell numbers. A second experiment examined the effect of 72 h of
      T-infusion on LHRH and POMC mRNA levels. Castrated yearling males were assigned
      to receive either vehicle (n = 4) or T (768 ug/kg/day; n = 4). Blood samples were
      collected at 10 min intervals for 4 h prior to and during the final 4 h of
      infusion. Infusion of T decreased (P < 0.01) mean LH and LH pulse frequency. T
      did not significantly affect (P > 0.10) silver grain area per LHRH neuron or LHRH
      cell numbers. T reduced (P < 0.01) silver grain area per POMC neuron without
      affecting (P > 0.10) POMC cell number. We reject our hypothesis and conclude that
      reduced LHRH or heightened POMC gene expression are not mechanisms whereby T
      reduces pulsatile LHRH release in male sheep.

PMID- 8868259
TI  - In vitro immunoneutralization of a cleaved prolactin variant: evidence for a
      local paracrine action of cleaved prolactin in the development of gonadotrophs
      and thyrotrophs in rat pituitary.
AB  - We have previously isolated a cleaved prolactin variant, secreted by rat
      pituitary cells in culture, that stimulated [3H]thymidine incorporation into DNA
      in gonadotrophs and thyrotrophs when added to pituitary aggregate cell cultures
      of 14-day-old female rats. Using synthetic peptides homologous to the new C- and
      N-termini of the cleavage site, we made antisera recognizing this cleaved variant
      without significant cross reaction with native prolactin. Addition of these
      antisera to pituitary aggregate cell cultures decreased [3H]thymidine
      incorporation into DNA in gonadotrophs and thyrotrophs but not in the other
      pituitary cell types. These data are further evidence that this prolactin
      variant, cleaved between Tyr-145 and Leu-146, may have an important role as
      growth regulator of the gonadotrophs and thyrotrophs in the rat pituitary.

PMID- 8868260
TI  - Corticosterone controls interleukin-1 beta expression and sickness behavior in
      the rat.
AB  - We studied the effect of corticosterone on interleukin (IL)-1 beta synthesis,
      body temperature, general activity, food consumption and fluid intake in rats
      treated with bacterial lipopolysaccharide (LPS). Radiotelemetry was used to
      assess body temperature and locomotor activity in combination with continuous
      automated recordings of feeding and drinking. This technique was developed as a
      novel method to identify and measure sickness behavior in rodents. The animals
      were (a) sham-operated, (b) adrenalectomized or (c) sham-operated and treated
      with corticosterone (10 mg/kg, subcutaneously). They were then intraperitoneally
      injected with vehicle or LPS at a dose (100 micrograms/kg) that in sham-operated
      rats induced fever and anorexia, reduced spontaneous activity and increased IL1
      beta mRNA in spleen and adrenals as determined by Northern blot analysis.
      Adrenalectomized rats produced larger amounts of splenic IL-1 beta mRNA, reduced
      their general activity much more and developed a mild adipsia as compared with
      adrenal-intact animals. Administration of corticosterone 1 h before LPS lowered
      the splenic IL-1 beta mRNA content compared to LPS-treated adrenal-intact rats
      that did not receive corticosterone and inhibited fever and anorexia, whereas the
      glucocorticoid did not attenuate the endotoxin-induced suppression of locomotor
      activity. Our data suggest that during inflammatory conditions body temperature,
      sickness behavior and the synthesis of IL-1 beta are controlled by
      corticosterone. Different components of sickness behavior seem to be
      independently regulated and are under differential control by glucocorticoids.

PMID- 8868261
TI  - Facilitatory effects of pituitary adenylate cyclase activating polypeptide
      (PACAP) on neurons in the magnocellular portion of the rat hypothalamic
      paraventricular nucleus (PVN) in vitro.
AB  - To establish the role of pituitary adenylate cyclase activating polypeptide
      (PACAP), a member of vasoactive intestinal polypeptide (VIP) family, as a
      neurotransmitter/neuromodulator in the central nervous system, the effects of
      PACAP38, PACAP27 and VIP on the single neuron activity in the magnocellular
      portion of the hypothalamic paraventricular nucleus (mg.PVN) were examined in rat
      brain slice preparations. Extracellular recordings were made from 111 neurons in
      the mg.PVN, which fired spontaneously at an average rate of 1.85 +/- 0.2 spikes/s
      (mean +/- SEM). PACAP38 and PACAP27 were applied to 78 and 33 of the 111 neurons,
      respectively. Perfusion with PACAP38 in doses between 10 nM and 1 microM
      increased the firing rate of 56 (71.8%) of the 78 neurons in a dose-dependent
      manner. The threshold dose of PACAP38 to excite the neurons seemed to lie below
      10 nM. The application of PACAP27 (1 microM) also increased the firing rate of 19
      (57.6%) of the 33 neurons tested. Eleven (52.4%) of 21 neurons which were excited
      by PACAP38 also showed excitation following perfusion with VIP (1 microM). The
      responses to PACAP38 in 12 of 20 neurons and those to VIP in 6 of 9 neurons
      tested were still observed in a low Ca2+ and high Mg2+ medium. Although there was
      no difference in the mean latency between the responses to PACAP38 (1 microM) and
      VIP (1 microM) (2.1 +/- 0.1 min and 2.4 +/- 0.4 min, respectively), the duration
      of the PACAP38-induced excitation (59.0 +/- 5.0 min) was much longer than that of
      the VIP-induced one (18.8 +/- 3.1 min). The PACAP38 (30 nM)-induced excitation
      was reversibly blocked by a concurrent application of PACAP5-38 (300 nM), a PACAP
      receptor antagonist. While a selective VIP receptor antagonist, [Lys1, Pro2,5,
      Arg3,4, Tyr6]-VIP (1 microM), did not affect the excitatory responses to PACAP38
      (300 nM), it completely blocked the VIP (1 microM)-induced excitation. These
      findings suggest that PACAP may therefore modulate the secretion of the pituitary
      hormones at least partly by its action on the neurons in the mg.PVN through the
      activation of specific receptors for PACAP.

PMID- 8868262
TI  - Prostaglandin fever in rats throughout the estrous cycle late pregnancy and post
      parturition.
AB  - We have examined the influence of natural variations in endocrine status on the
      ability to generate a prostaglandin-induced fever in virgin female, pregnant and
      lactating rats and compared responses to those in male rats. Endocrine status of
      virgin female rats was assessed from examination of vaginal smears and time of
      parturition noted to enable accurate dating of pre- and postparturient fevers.
      Unanesthetized rats, previously prepared with intraventricular guide cannulas and
      intraperitoneal telemetry thermistors, were given intraventricular injections of
      prostaglandin E1 (2-100 ng/5 microliters) and temperatures monitored for 3 h
      after injection. Virgin females developed significantly larger fevers than did
      males at higher doses. There were no significant alterations in either fever
      height or duration as a function of the phase of the reproductive cycle in the
      females. Both pregnant and postparturient rats within the several days around
      birth displayed significantly lower fevers than did virgin females, but there was
      no further reduction in the immediate periparturient period. These data indicate
      that there are sex-, and possibly hormone-dependent differences in the central
      mechanisms involved in fever generation and antipyresis.

PMID- 8868263
TI  - Adrenergic receptor activation hyperpolarizes the caudal neurosecretory cells of
      the flounder, Platichthys flesus.
AB  - The physiological factors that govern activity of the caudal neurosecretory
      system in teleost fish are poorly understood. Immunocytochemical evidence
      indicates that the neurosecretory Dahlgren cells are innervated by descending
      monoaminergic fibres. Using intracellular recording techniques in an isolated
      preparation of the posterior spinal cord of the flounder (Platichthys flesus) we
      have demonstrated that superfusion of adrenaline or noradrenaline (10(-7) - 10(
      3) M) causes hyperpolarization of Dahlgren cells (up to -30 mV). This
      hyperpolarization is likely to reflect an inhibitory effect of noradrenergic
      nerves on the neurosecretory system in vivo, reducing the rate of hormone
      release. Fluctuations in the input resistance and membrane time constant suggest
      involvement of a multiplicity of cellular mechanisms, including the opening and
      closing of populations of ion-selective channels. Superfusion with dopamine (10(
      7) - 10(-3) M) had no effect. Superfusion with the beta-adrenoreceptor agonist,
      isoprenaline, caused hyperpolarization but to a markedly lesser extent than the
      maximum effect of adrenaline or noradrenaline, suggesting that their effects are
      mediated, only in part, by a beta-adrenoreceptor subtype. Superfusion of the
      preparation with a membrane permeable, non-hydrolysable cyclic AMP analogue (8-[4
      chlorophenylthio]-cAMP) resulted in a slight hyperpolarization which was
      accompanied by a small, but significant, increase in input resistance. These data
      are consistent with at least part of the beta-adrenoreceptor mediated effect
      involving closure of cAMP-sensitive ion channels. Superfusion with the alpha 1
      adrenoreceptor agonist, phenylephrine, had no effect on any electrophysiological
      parameter studied. However, the alpha 2-adrenoreceptor agonist, clonidine, caused
      hyperpolarization which again failed to reach the maximum level produced by
      adrenaline or noradrenaline. Together, these data suggest that the adrenergic
      inhibition of Dahlgren cell activity is mediated by both alpha 2- and beta
      adrenoreceptor subtypes.

PMID- 8868264
TI  - Effect of increased interstitial fluid flux on fractional catabolic rate of high
      molecular weight [3H]hyaluronan injected in rabbit skin.
AB  - The removal rate of high molecular weight (M(r) 3 x 10(6) [3H]hyaluronan has been
      measured in rabbit paw skin in control and during increased local venous pressure
      induced by ligation of the femoral vein. The increased venous pressure resulted
      in a 20% increase of interstitial volume at 4 h after ligation, a value which
      relates to at least a doubling of lymph flow, i.e. also to doubling of fluid flux
      through the tissues. The fractional catabolic rate of hyaluronan was 0.0918 +/-
      0.0170 h-1 (n = 10) and 0.0775 +/- 0.0206 h-1 (n = 11) in control and following
      increased venous pressure respectively (P > 0.05). Since the fractional catabolic
      rate of hyaluronan is not affected by increased venous pressure, the removal of
      hyaluronan via lymphatic drainage in rabbit paw skin must be small compared to
      the local turnover of the polysaccharide.

PMID- 8868265
TI  - Extract of the marine alga Prymnesium patelliferum induces release of
      acetylcholine from cholinergic nerves in the rat bronchial smooth muscle.
AB  - An extract of the marine algal flagellate Prymnesium patelliferum enhanced the
      spontaneous as well as the K+ evoked (51 mM K+) release of [3H]acetylcholine and
      endogenous acetylcholine from autonomic cholinergic nerves of rat bronchial
      smooth muscle. The effects were concentration-dependent and reversible. The
      enhancement of the K+ evoked release by the algal extract was partly dependent on
      extracellular Ca2+ and was significantly suppressed by the organic Ca2+ blockers
      omega-conotoxin GVIA (1 microM), diltiazem (100 microM), nifedipine (100 microM)
      and flunarizine (100 microM). The enhancement of the spontaneous release seemed
      Ca2+ independent and not sensitive to the Na+ channel blocker tetrodotoxin.
      Sphingosine (20 microM), a protein kinase C inhibitor, strongly potentiated the
      enhancement of spontaneous release of [3H]acetylcholine induced by the algal
      extract whereas another protein kinase C inhibitor. 1-(5-quinolinesulphonyl)-2
      methylpiperazine (H-7) (20 microM), was without effect. A similar potentiation as
      seen with sphingosine was observed with procaine (100 microM) and flunarizine
      (100 microM). The results indicate that the enhancement of the K+ evoked release
      of [3H]acetylcholine by the toxic extract of P. patelliferum was partly caused by
      activation of voltage-dependent Ca2+ channels. The increase in the spontaneous
      release of [3H]acetylcholine and endogenous acetylcholine induced by the algal
      extract alone may be caused by an ionophore-like property of the algal extract.
      This effect of the algal extract may be enhanced by compounds that facilitate the
      interaction of the algal toxin with the plasma membrane such as the lipophilic
      compounds flunarizine, procaine and sphingosine.

PMID- 8868266
TI  - Apical secretion of rat submandibular tissue kallikrein continues in the absence
      of external stimulation: evidence for a constitutive secretory pathway.
AB  - Sequential samples of saliva evoked by low frequency parasympathetic nerve
      stimulation were collected from cannulated submandibular ducts of anaesthetized
      rats following periods of varying length without stimulation. After such rest
      periods the first samples of saliva were found to contain much higher levels of
      tissue kallikrein (rK1) activity and protein than the ensuing samples from the
      same stimulation period and the latter contained levels similar to those found
      previously in parasympathetically-evoked saliva. rK1 activity in first samples
      increased with the length of the preceding interval, indicating that a continuous
      secretion of rK1 occurs from ductal cells into glandular lumina and accumulates
      there in the absence of stimulation or fluid secretion. The protein secretory
      pattern following rest pauses was unaffected by alpha-adrenergic receptor
      blockade and a high percentage of the proteinase activity was resistant to soya
      bean trypsin inhibitor, showing that the secretion was not caused by exocytosis
      of storage granules from ductal cells and therefore was likely to be a result of
      a constitutive secretion of newly synthesized enzyme. The pattern of continuous
      secretion into lumina detected for total protein in the absence of stimulation,
      suggests that other secretory proteins may also be secreted similarly but at
      different rates.

PMID- 8868267
TI  - Effects of hCGRP 8-37 and the NK1-receptor antagonist SR 140.333 on capsaicin
      evoked vasodilation in the pig nasal mucosa in vivo.
AB  - A novel pig in vivo model was used to study vascular effects of capsaicin,
      substance P and calcitonin gene-related peptide (CGRP) in the nasal mucosa and
      skin. An acoustic rhinometer was used to measure changes in nasal cavity volume,
      mainly representing changes in capacitance vessels in the vascular beds. The non
      peptide NK1-receptor antagonist SR 140.333 and the CGRP-receptor antagonist hCGRP
      8-37 were used to investigate the role of substance P and CGRP, respectively, in
      capsaicin-evoked vasodilation mediated through activation of sensory C-fibre
      afferents. In this study we show that SR 140.333 is a potent inhibitor of
      substance P-induced vasodilation in the nasal mucosa whereas it has no effect on
      the capsaicin-evoked responses. Substance P only elicited a minor and
      shortlasting increase in superficial skin blood flow; this response, however, was
      completely blocked after administration of SR 140.333. Capsaicin-evoked
      vasodilation in the skin was slightly reduced by SR 140.333. CGRP-induced
      vasodilation in the nasal mucosa and skin was of much longer duration than the
      substance P-induced response, and was thus similar to the vascular effects
      mediated by capsaicin. hCGRP 8-37 significantly reduced both the CGRP- and
      capsaicin-mediated vasodilation in the nasal mucosa and the decrease of nasal
      cavity volume. Although the peak vasodilation in the skin in response to
      capsaicin, was unaltered by blockade of CGRP-receptors, the integrated response
      was significantly reduced by hCGRP 8-37. The present results show that
      vasodilatory responses to activation of afferent nerves in the pig nasal mucosa
      and superficial skin are mainly dependent on CGRP, while NK1-receptor mechanisms
      seem to be of no or minor importance.

PMID- 8868268
TI  - Specificity of training velocity and training load on gains in isokinetic knee
      joint strength.
AB  - The present study investigated the effects of three different strength training
      regimes on the isokinetic strength profile of the knee extensors (quadriceps, Q)
      and flexors (hamstrings, H) and if increases in isokinetic strength were
      accompanied by an enhanced performance during a more complex leg movement, the
      soccer kick. Twenty-two elite soccer players performed 12 weeks of strength
      training (three times per week) at either high resistance (HR group: 4 sets, 8
      reps, 8RM loading), low resistance (LR group: 4 sets, 24 reps, 24RM loading),
      loaded kicking movements (LK group: 4 sets, 16 reps, 16RM loading) while one
      group served as controls (CO group). Isokinetic concentric and eccentric moment
      of force was obtained (KinCom) as peak moment (Mpeak) and moment at 50 degrees
      knee flexion (M50) at angular velocities of 30, 120, 240 degrees s-1. Isokinetic
      knee joint strength was unchanged in groups LR, LK, CO. However, after the HR
      strength training, concentric Mpeak (+/- SD) increased (P < 0.01) at 30 degrees s
      1 (Q, 258 +/- 37 to 297 +/- 57 Nm; H, 122 +/- 22 to 140 +/- 21 Nm). Furthermore,
      eccentric Mpeak increased at 30, 120 and 240 degrees s-1 (Q, 274 +/- 60 to 345 +/
      57 Nm (P < 0.01), 291 +/- 56 to 309 +/- 49 Nm and 275 +/- 43 to 293 +/- 36 Nm (P
      < 0.05), respectively; H, 143 +/- 32 to 158 +/- 25 Nm, 152 +/- 39 to 169 +/- 31
      Nm and 148 +/- 27 to 163 +/- 19 Nm (P < 0.05)). Corresponding increases (P <
      0.05) were observed for M50. The H/Q ratio calculated as eccentric hamstring
      strength divided by concentric quadriceps strength (Hecc/Qcon, representative for
      knee extension) at 240 degrees s-1 increased (P < 0.05) from 107 to 118% (based
      on Mpeak) and from 90 to 105% (M50). Kicking performance estimated by maximal
      ball flight velocity was unaffected by any of the strength training regimes
      investigated. In conclusion, only heavy-resistance strength training induced
      increases in isokinetic muscle strength in the absence of learning effects.
      Concentric strength gains were observed at the actual velocity of training, while
      eccentric strength gains were found over the entire range of velocities examined.
      The capacity of the hamstring muscles for providing stability to the knee joint
      during fast extension was augmented as a result of the heavy-resistance strength
      training. Strength training should be integrated with other types of training
      involving the actual movement pattern in order to increase the performance within
      more complex movement patterns.

PMID- 8868269
TI  - Proximal tubular lithium/plasma concentration ratio depends on tubular fluid flow
      rate.
AB  - Previous studies have given slightly different values of proximal tubular
      fluid/plasma lithium concentration ratios (TF/P)Li. The aim of the present study
      was to investigate whether the technique of tubular fluid collection by
      micropuncture might contribute to this difference. Early distal and late proximal
      tubular fluid was collected by micropuncture during recording of early proximal
      hydrostatic pressure with varying pressures applied to the collection pipette.
      Distal fluid collection with 2-3 mmHg suction was unable to influence distal
      flow, proximal tubular pressure, nephron filtration rate (SNGFR), (TF/P)Li or
      (TF/P)Na significantly, as compared with values obtained without suction. In
      contrast, during late proximal collections, tubular pressure could be controlled.
      Within the range 2 mmHg below to 6 mmHg above free flow pressure maintained
      during collection, proximal flow rate varied from 9 to 44 nL min-1. (TF/P)Li was
      positively and significantly correlated to late proximal flow rate (P < 0.005, r
      = 0.65), independent of tubular pressure. (TF/P)Na was 1.03 and independent of
      flow rate and pressure. With collection adjusted to a late proximal flow of 24 nL
      min-1. (TF/P)Li would be about 1.15. At the more physiological flow rate of 12-14
      nL min-1, (TF/P)Li was not significantly different from 1.00. It is concluded
      that proximal Li transport is distinct from Na transport and lags behind Na and
      water transfer only when flow rate is increased above normal. The result
      emphasizes the importance of the micropuncture fluid collection technique for
      estimates of proximal (TF/P)Li.

PMID- 8868270
TI  - Effects of acute and chronic unilateral renal denervation on the tubuloglomerular
      feedback mechanism.
AB  - We recently observed a time-dependent resetting of the tubuloglomerular feedback
      (TGF) sensitivity to a subnormal level after acute unilateral renal denervation
      (aDNX). The present investigation compares the effects of aDNX with those of
      chronic unilateral renal denervation (cDNX), i.e one week after aDNX. All
      experiments were performed in anaesthetized rats prepared for micropuncture. cDNX
      led to increases in urine, sodium and potassium excretion in denervated kidneys,
      while contralateral kidneys showed reduced excretion of these parameters. GFR was
      increased in denervated kidneys, but unchanged on the contralateral side. TGF
      activity was determined by measuring the maximal stop-flow pressure response
      (delta Psf) and the tubular flow rate at which 50% of the maximal response
      occurred (turning point; TP). cDNX decreased TGF sensitivity, as indicated by an
      increased TP from 19.1 nL/min in sham-DNX to 26.1 nL/min. Concomitantly, TP in
      contralateral kidneys was significantly decreased to 15.9 nL/min, aDNX led to a
      greater sensitivity reduction: TP increased from 19.8 to 34.0 nL/min and
      contralaterally TP decreased to 14.0 nL/min. delta Psf in cDNX increased by 63%
      compared to sham-DNX, while on the contralateral side this was unchanged. No
      difference in delta Psf was found between control, DNX and contralateral kidneys
      in the aDNX group. In summary, these experiments show that the previously
      reported decrease in TGF sensitivity in aDNX kidneys still persists after one
      week, although less pronounced. As a result of the decreased TGF sensitivity, GFR
      is kept on a high level in cDNX kidneys. Contralateral kidneys show reversed
      resetting.

PMID- 8868271
TI  - Sulfonylureas enhance GABAA synaptic potentials in rat midbrain dopamine
      neurones.

PMID- 8868272
TI  - Secondary bioenergetic failure after transient focal ischaemia is due to
      mitochondrial injury.

PMID- 8868273
TI  - Inotropic effect of adrenomedullin in the isolated perfused rat heart.

PMID- 8868274
TI  - Deficits in spatial working memory after unilateral temporal lobectomy in man.
AB  - Forty neurosurgical patients and 20 controls were tested on a series of
      computerized tasks (the executive golf, structured golf and rotate tasks)
      designed to investigate spatial working memory. As defined by Olton [Spatial
      Abilities, Academic Press, New York, 1982], spatial working memory involves the
      encoding of specific and contextual information within the spatial domain. Right
      temporal lobectomy patients were significantly impaired on all three tasks, while
      the left temporal lobectomy patients showed a less significant overall impairment
      only on the structured golf task. Although there was no statistically significant
      differences between the two patient groups on the three tasks, the results point
      towards a robust deficit in spatial memory associated with right temporal
      lobectomy. The results provide further evidence for the role of the mesial
      temporal lobe structures in the processing and encoding of spatial information.

PMID- 8868275
TI  - Recency effect in anterograde amnesia: evidence for distinct memory stores
      underlying enhanced retrieval of terminal items in immediate and delayed recall
      paradigms.
AB  - This study was devised to investigate immediate and delayed recency effects in
      anterograde amnesic patients. For this purpose, a word-list immediate recall
      paradigm and a modified version of the procedure devised by Baddeley and Hitch
      [Attention and Performance, Erlbaum, NJ, 1977] for eliciting the recency effect
      in delayed recall conditions was administered to a sample of amnesic patients and
      to a group of age-matched healthy subjects. Amnesics disclosed a fully normal
      recency effect in the immediate recall paradigm and a deficient recency effect in
      the delayed recall condition. These data, taken together with experimental
      evidence from a patient affected by a pure form of phonological short-term memory
      impairment [35], draw a double neuropsychological dissociation suggesting a
      differential origin for the two kinds of recency effects: a short-term memory
      output underlying enhanced recall of terminal items in immediate recall
      paradigms, and an ordinal retrieval strategy applied to long-term memory stored
      units at the root of the delayed recency effect.

PMID- 8868276
TI  - Encoding words and pictures: a positron emission tomography study.
AB  - Subjects viewed words, pictures, crosshairs, or a large X flanked by two smaller
      xs on either side while their brain activity was monitored using positron
      emission tomography (PET). When activation from the pictures, crosshairs, or Xs
      condition was subtracted from activation in the words condition, the left angular
      gyrus and Broca's area were found to be activated. In the comparison of words and
      pictures, additional language areas were activated. These results provide support
      for the classical neurological model of reading. The results also suggest that a
      "word form area" is near the margin of the left angular gyrus.

PMID- 8868277
TI  - Examination of the working memory components in normal aging and in dementia of
      the Alzheimer type.
AB  - The verbal and attentional components of working memory were examined in patients
      with Alzheimer's disease, normal elderlies, and young controls. Patients with
      Alzheimer's disease, showed a reduced span but were sensitive to word length.
      This is indicative of a functional rehearsal procedure. However, the effect of
      phonological similarity on immediate recall was smaller in patients with
      Alzheimer's disease and these patients showed a depressed performance in tasks of
      phonological analysis. There was also a significant decrement in a task that
      assessed the attentional component of working memory. Examination of individual
      patterns of performance showed that the phonological deficiency was severe in a
      subgroup of patients while the attentional deficit was more general.

PMID- 8868278
TI  - Spatial locations gone awry: object and spatial memory deficits in children with
      fetal alcohol syndrome.
AB  - Hippocampus vulnerability following gestational alcohol exposure has been
      demonstrated neuroanatomically and behaviorally in animal models of fetal alcohol
      syndrome (FAS). There has been no similar demonstrations in humans. The Smith and
      Milner (1981) Memory for 16 Objects task has been used to explore the effects of
      right vs left temporal lobectomy with varying degrees of damage to the
      hippocampus. In the present experiment, this same task was administered to 15
      children with FAS (mean age 10.03, S.D. = 2.33) and 15 control children (mean age
      10.02, S.D. = 2.31). Similar to patients with right temporal lobectomies and a
      large excision to the hippocampus, children with FAS were able to perform
      immediate but not delayed object recall, had a general spatial memory deficit (P
      < 0.05), and significantly distorted the spatial array (P < 0.05). Although these
      results are consistent with an interpretation of hippocampal dysfunction,
      gestational alcohol exposure is known to result in a wide-ranging spectrum of
      neuropsychological deficits that vary in both extent and severity. Visuospatial
      deficits on the Beery test of Visuomotor Integration and Clock Drawing are
      suggestive of the other neural regions that may be involved in producing the
      behavioral deficits in children with FAS.

PMID- 8868279
TI  - Salivary testosterone levels in left- and right-handed adults.
AB  - It has been proposed that prenatal testosterone (T) may contribute to the
      development of hand preference and cerebral functional asymmetry in humans. To
      investigate any persisting association between T and asymmetry in adulthood, left
      handed (LH) and right-handed (RH) men and women were administered a hand
      preference questionnaire and the Fused Dichotic Words Test. Testosterone was
      measured in samples of saliva. Results showed that LH subjects of both sexes had
      lower salivary T concentrations than their RH counterparts. Among LH males,
      subjects with a right-ear advantage in dichotic listening tended to have lower T
      concentrations than subjects with a left-ear advantage. These results are
      consistent with the notion that T may be involved in the development of hand
      preference and cerebral functional asymmetry.

PMID- 8868280
TI  - Consequences of covert orienting to non-informative stimuli of different
      modalities: a unitary mechanism?
AB  - Reaction time (RT) to visual targets is lengthened following non-informative cues
      presented in the same location, or in different locations but in the same
      hemifield as the targets. RT lengthening is best accounted for by the voluntary
      suppression of an overt orienting toward the location of the cue: this veto
      produces an inhibition of the overall motor reactivity towards stimuli presented
      in the entire hemifield of the cue. This paper shows that ipsilateral inhibition
      is not unique to the visual system, since the same directional constraints in
      motor readiness are induced with somatosensory stimulation. RT is slower when a
      somatic target delivered on a shoulder is preceded by an ipsilateral somatic cue
      compared to a contralateral one. The neural control of these orienting tendencies
      may involve the superior colliculus, which contains overlapping maps of the
      visual, somatosensory and auditory peripheries. This suggestion is reinforced by
      the presence of cross-modal inhibitory effects in paradigms involving visual cues
      and somatic targets or somatic cues and visual targets. While the time course of
      ipsilateral inhibition is similar in the visual and the somatic modalities, cross
      modal inhibitory effects are different and somehow complementary when visual cues
      precede somatic targets (early short-lasting inhibition) or, respectively,
      somatic cues precede visual targets (late, long-lasting inhibition). An
      additional finding is that crossed-uncrossed RT differences (CUDs), presumably
      due to the anatomical relations between stimulus and response, are present in
      both modalities.

PMID- 8868281
TI  - Evaluation of dithiol chelating agents as potential adjuvants for anti-IL-2
      receptor lead or bismuth alpha radioimmunotherapy.
AB  - The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DMPS) and
      meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential
      adjuvants to reduce or prevent radiotoxicity in anti-interleukin-2 receptor (IL
      2R) Lead-212 or Bismuth-212 alpha-radioimmunotherapy. DMPS was less toxic than
      DMSA to tumor cell lines in culture. No adverse effects on the ability of an anti
      IL-2R monoclonal antibody (MAb) to bind to its specific antigen were detected
      using DMPS or DMSA at concentrations up to 600 ug/mL in 10% or 100% mouse serum.
      After a 5-day oral administration of chelating agent, neither acute nor chronic
      toxicities on blood hematology, blood chemistry or organ weights were observed
      for treated mice. DMPS and DMSA were effective in accelerating whole body
      clearance of the gamma-emitting tracer Bismuth-206. Both chelates significantly
      reduced femur uptake of tracer when compared to nontreated control mice. However,
      only DMPS prevented early (2 h postinjection) renal accumulation. These studies
      support the use of DMPS as a potential adjuvant chelation therapy in Lead-212 or
      Bismuth-212 radioimmunotherapy protocols.

PMID- 8868282
TI  - Technetium-99m radiolabeled ouabagenin-cysteine conjugate: biological evaluation
      in animal models.
AB  - Two ouabagenin-cysteine conjugates were synthesized by condensing 3-beta
      monochloroacetyl and 3-beta, 11-alpha dichloroacetyl ouabagenin with cysteine.
      The resulting ligands were radiolabeled with technetium-99m (99mTc) to furnish a
      single homogenous 99mTc chelate in each case with good stability. The animal
      experiments with these 99mTc-labeled conjugates established the superiority of
      guinea pig over rat and rabbit as an animal model, as previously observed for
      other tritiated or radioidinated cardiac glycosides or aglycones. In
      biodistribution experiments in guinea pig, these 99mTc chelates showed a
      favorable heart to liver (and other nontarget organ) uptake ratio, comparable to
      that of recently reported 125I-digoxigenin iodohistamine-3-oxime. The low heart
      to blood ratio in animal experiments with ouabagenin derivatives could be
      attributed to the absence of 3-beta sugar residues in these molecules, which is
      in agreement with the previous observation reported in connection with
      radioiodinated digoxin and digoxigenin derivatives.

PMID- 8868283
TI  - Synthesis, in vitro binding profile and biodistribution of a 125I-labeled N
      benzyl pyrrolidinyl benzamide derivative: a potential radioligand for mapping
      dopamine D2 receptors.
AB  - cis-N-(1-Benzyl-2-methylpyrrolidine-3-yl)-5-iodo-2-methoxy-4-(methylamin o)
      benzamide (IYM), a YM-09151-2 analog iodinated at the 5-position of the benzoyl
      moiety, was synthesized and evaluated as a potential radiopharmaceutical for
      investigating brain dopamine D2 receptors by single photon emission computer
      tomography (SPECT). [125I]IYM was synthesized by a halogen exchange reaction and
      purified by high-performance liquid chromatography (HPLC). An in vitro
      competitive binding study with [3H]spiperone using rat striatal synaptosomal
      membranes revealed that IYM had higher affinity for dopamine D2 receptors than
      did YM-09151-2 or spiperone. In a saturation binding study using rat striatal
      synaptosomal membranes, IYM had a Kd of 0.04 nM. Biodistribution studies in mice
      disclosed that [125I]IYM exhibited high and specific striatal uptake, with the
      striatal/cerebellar uptake ratio being 14 at 120 min after injection.
      Furthermore, the striatal uptake of [125I]IYM was saturable, and [125I]IYM was
      displaced only by dopaminergic compounds. Ex vivo autoradiographic studies in
      rats further confirmed the high uptake and retention of this agent in the
      striatum and total blockade of its uptake by YM-09151-2. Thus, IYM showed
      specific binding to dopamine D2 receptors in the rodent striatum and therefore
      holds great potential for use in in vivo dopamine D2 receptor studies.

PMID- 8868284
TI  - Stability of a metabolizable ester bond in radioimmunoconjugates.
AB  - Ester bonds have been used as metabolizable linkages to reduce radioactivity
      levels in non-target tissues following the administration of antibodies labeled
      with metallic radionuclides. In this radiochemical design of antibodies, while
      the ester bonds should be cleaved rapidly in non-target tissues, high stability
      of the ester bonds in plasma is also required to preserve target radioactivity
      levels. To assess the structural requirements to stabilize the ester bond, a new
      benzyl-EDTA-derived bifunctional chelating agent with an ester bond, (1-[4-[4-(2-
      maleimidoethoxy)succinamido]benzyl]ethylenediamine-N,N,N',N' -tetraacetic acid;
      MESS-Bz-EDTA), was developed. MESS-Bz-EDTA was coupled with a thiolated
      monoclonal antibody (OST7, IgG1) prepared by reducing its disulfide bonds to
      introduce the ester bond close and proximal to the antibody molecule. For
      comparison, 1-[4-(5- maleimidopentyl)aminobenzyl]ethylenediamine-N,N,N',N'
      tetraacetic acid (EMCS-Bz-EDTA) and meleimidoethyl 3-[131I]iodohippurate (MIH)
      was coupled to OST7 under the same conjunction chemistry. When incubated in 50%
      murine plasma or a buffered-solution of neutral pH, OST7-MESS-Bz-EDTA-111In
      rapidly released the radioactivity, and more than 95% of the initial
      radioactivity was liberated after a 24 h incubation in both solutions, due to a
      cleavage of the ester bond. On the other hand, only about 20% of the
      radioactivity was released from OST7-MIH-131I in both solutions during the same
      incubation period. In mice biodistribution studies, while a slightly faster
      radioactivity clearance from the blood with less radioactivity levels in the
      liver and kidneys was observed with OST7-MIH-131I than with OST7-EMCS-Bz-EDTA
      111In, OST7-MESS-Bz-EDTA-111In indicated radioactivity clearance from the blood
      much faster than and almost comparable to that of OST7-MIH-131I and
      succinamidobenzyl-EDTA-111In, respectively. These findings as well as previous
      findings on radiolabeled antibodies with ester bonds suggested that while an
      introduction of an ester bond close to an antibody molecule stabilized the ester
      bond against esterase access, chemical structures of the linkages and radiolabels
      attached to the ester bonds play a significant role in the chemical stability of
      the ester bond. This may explain the different stability of the ester bonds in
      radioimmunoconjugates so far reported.

PMID- 8868285
TI  - Effect of induced hypertension with angiotensin II infusion on biodistribution of
      111in-labeled monoclonal antibody.
AB  - We investigated whether induced hypertension could enhance tumor uptake of
      monoclonal antibody. 111In-DTPA-A7 (IgG1 against 40kD tumor associated
      glycoprotein) was injected into colon carcinoma xenografted mice which were
      subcutaneously implanted with micro-osmotic pump containing angiotensin II (AT
      II). Biodistribution was observed in groups of mice infused with AT-II at rate of
      0.5 micrograms/kg/min (L) or 1 microgram/kg/min (H) and compared with a group of
      mice infused with saline (S). Tumor uptake of 111In-A7 in L and H was 1.32 and
      1.57 times greater than S at 48 h after intravenous injection of A7. Normal organ
      uptakes also tended to be increased by AT-II infusion. Further study is needed to
      get optimum effect of hypertensive treatment on biodistribution of radiolabeled
      MoAb.

PMID- 8868286
TI  - In vivo evaluation of [11C]- and [18F]-labelled cocaine analogues as potential
      dopamine transporter ligands for positron emission tomography.
AB  - Four analogues of the potent dopamine transporter ligand, WIN 35,428, were
      radiolabelled with 11C and 18F at the 2-beta-carboxy position for evaluation as
      potential ligands for imaging dopamine uptake sites by positron emission
      tomography (PET) namely, methyl (1R-2-exo-3-exo)-8- methyl-3-(4-methylphenyl)-8
      azabicyclo[3.2.1]octane-2-carboxylate (RTI-32), its 4-chlorophenyl analogue (RTI
      31), 2'-fluoroethyl (1R-2-exo-3-exo)-8-methyl-3-(4-methylphenyl)-8
      azabicyclo[3.2.1]octane-2 - carboxylate (FETT) and its 4-chlorophenyl analogue
      (FECT). Upon intravenous injection in rats, all four radiotracers displayed
      preferential accumulation of radioactivity in regions known to contain high
      concentrations of dopamine uptake sites. Competition studies with two of the
      analogues, [11C]RTI-32 and [18F]FETT, demonstrated that, for both radiotracers,
      binding was saturable and displayed the appropriate pharmacology as potential PET
      ligands for imaging the dopamine transporter. Striatum to cerebellar ratios for
      [11C]RTI-32 (at 90 min post-injection) and [18F]FETT (at 120 min post-injection)
      were 27 and 21, respectively.

PMID- 8868287
TI  - Radiosynthesis of [123I]N-methyl-4-iododexetimide and [123I]N-methyl-4
      iodolevetimide: in vitro and in vivo characterisation of binding to muscarinic
      receptors in the rat heart.
AB  - [123I]N-methyl-4-iododexetimide, [123I]MIDEX, and its pharmacologically inactive
      enantiomer [123I]N-methyl-4-iodolevetimide, [123I]MILEV were prepared via
      electrophilic iododesilylation using Chloramine-T as oxidising agent followed by
      N-methylation using methyl iodide. The radiotracers were purified with semi
      preparative HPLC with radiochemical yields of 80 +/- 11% (n = 6). The average
      time of synthesis was 100 min with specific activity > 2000 Ci/mmol. In vitro,
      the binding of [123I]MIDEX, after addition of carrier, measured on homogenates of
      rat atrium was Bmax = 4.5 +/- 0.4 pmol/mg protein, Kd = 3.3 +/- 0.2 nM while in
      the ventricle Bmax = 2.3 +/- 0.2 pmol/mg protein, Kd = 4.0 +/- 1.4 nM. In vitro,
      the binding of [123I]MILEV was non-specific. The in vivo biodistribution of
      [123I]MIDEX showed high uptake in the atrium (3.2% ID/g) and left and right
      ventricles (2.2, 2.5% ID/g respectively) at 5 min followed by clearance. High
      heart-to-lung and moderate liver-to-lung ratios were obtained during 60 min.
      Radioactivity in the atrium and ventricles was reduced by pre-administration of
      the m-AChR antagonist MQNB (1 mg/kg). Pretreatment of rats with other m-AChR
      ligands, pirenzapine (M1), methoctramine (M2) and 4-DAMP (M3) also resulted in
      reduction of [123I]MIDEX uptake with methoctramine being the most potent.
      [123I]MIDEX distribution in the rat heart was not significantly inhibited by pre
      administration of selective adrenergic drugs. The uptake was highly
      stereoselective since the inactive enantiomer, [123I]MILEV, demonstrated very low
      myocardial retention. The stability of [123I]MIDEX was evaluated by performing a
      metabolite study on atrium samples which revealed unchanged radiotracer 60 min
      postinjection. These results suggest that [123I]MIDEX may be a useful single
      photon agent for in vivo imaging of myocardial m-AChR in humans with [123I]MILEV
      offering the potential of assessing non-specific binding of the active tracer.

PMID- 8868288
TI  - In vitro evaluation of N-(fluoro)isopropyl norephedrine as potential cardiac
      imaging agents for PET.
AB  - N-Isopropylnorephedrine (INE) and N-fluoroisopropylnorephedrine (FINE) were found
      to have a poor affinity for either beta-adrenoceptors and the norepinephrine
      carrier protein. The low affinity of both compounds for Uptake-1 is probably due
      to the introduction of a bulky substituent on the nitrogen atom. It is concluded
      that INE and FINE cannot be used for cardiac imaging with PET.

PMID- 8868289
TI  - (S,S)- and (S,R)-1'-[18F]fluorocarazolol, ligands for the visualization of
      pulmonary beta-adrenergic receptors with PET.
AB  - The beta-adrenoceptor antagonist carazolol has been labelled with fluorine-18 in
      the isopropyl group via a reductive alkylation by [18F]-fluoroacetone of the
      corresponding (S)-desisopropyl compound according to a known procedure. The
      introduction of fluorine in the isopropyl group creates a new stereogenic centre
      resulting in the formation of (S,S)- and (S,R)-1'-[18F]fluorocarazolol, which
      were separated by HPLC. Tissue distribution studies were performed in male Wistar
      rats. Both the (S,S)- and (S,R)-diastereomers (S.A. 500-2000 Ci/mmol; 18.5-74
      TBq/mmol) showed high uptake in lung and heart, which could be blocked by
      pretreatment of the animals with (+/-)-propranolol. No significant differences
      were observed between the biodistribution of the two diastereomers. Metabolite
      analysis showed a rapid appearance of polar metabolites in plasma, while at 60
      min postinjection 92% and 82% of the total radioactivity in lung and heart was
      unmetabolized 1'-[18F]fluorocarazolol. In a PET-study with male Wistar rats, the
      lungs were clearly visualized and the pulmonary uptake was decreased after
      pretreatment of the animals with (+/-)-propranolol. The heart could not be
      visualized. Similar results were obtained in PET-studies with lambs.

PMID- 8868290
TI  - Specific in vivo binding in the rat brain of [18F]RP 62203: a selective 5-HT2A
      receptor radioligand for positron emission tomography.
AB  - In vivo pharmacokinetic and brain binding characteristics of [18F]RP 62203, a
      selective high-affinity serotonergic 5-HT2A receptor antagonist, were assessed in
      the rat following intravenous injection of trace amount of the radioligand. The
      radioactive distribution profile observed in the brain 60 min after injection was
      characterized by greater than fourfold higher uptake in neocortex as compared to
      cerebellum (0.38 +/- 0.07% injected dose/g, % ID/g and 0.08 +/- 0.01 ID/g,
      respectively), consistent with in vivo specific binding to the 5-HT2A receptor.
      Furthermore, specific [18F]RP 62203 binding significantly correlated with the
      reported in vitro distribution of 5-HT2A receptors, but not with known
      concentration profiles of dopaminergic D2 or adrenergic alpha 1 receptors.
      Finally, detectable specific binding was abolished by pretreatment with large
      doses of ritanserin, a selective 5-HT2A antagonist, which resulted in uniform
      uptakes across cortical, striatal and cerebellar tissues. Thus, [18F]RP 62203
      appears to be a promising selective tool to visualize and quantify 5-HT2A brain
      receptors in vivo with positron emission tomography.

PMID- 8868291
TI  - In vivo binding, pharmacokinetics and metabolism of the selective M2 muscarinic
      antagonists [3H]AF-DX 116 and [3H]AF-DX 384 in the anesthetized rat.
AB  - The pharmacokinetics, in vivo binding and metabolism of two M2 muscarinic
      receptor antagonists, [3H]AF-DX 116 and [3H]AF-DX 384, were studied in
      anesthetized rats, which received either the tracer alone or following a
      saturating injection of atropine. Both radioligands were cleared from the
      circulation with distribution half-lives of 17 and 14 sec and elimination half
      lives of 17 and 40 min for [3H]AF-DX 116 and [3H]AF-DX 384, respectively. A
      radioactive distribution, predominant in peripheral organs when compared to
      brain, was found at each time studied after tracer injection. Atropine
      displaceable tracer uptake was evidenced at 20-40 min in brain (31%),
      submandibular glands (26%), spleen (37%) and notably heart (55%) for [3H]AF-DX
      116 but only in heart (50%) for [3H]AF-DX 384 at 10-20 min. Regional brain
      sampling revealed a relatively uniform distribution of [3H]AF-DX 384 and a -45%
      atropine saturation effect (i.e., specific binding) in the thalamus 20 min after
      injection. Sequential thin-layer chromatographic studies performed on tissue
      extracts demonstrated the rapid appearance of labeled metabolites of both
      radiotracers in brain (but less so in liver) and especially in cardiac tissues,
      where almost 70% of total radioactivity still corresponded to authentic tracer 40
      min after injection. Thus, based on their low blood-brain barrier permeability
      and the high presence of labeled metabolites in the central nervous system, AF-DX
      116 and AF-DX 384 might be more helpful in the study of M2 muscarinic receptors
      present in heart rather than brain. Labeled with positron emittors, these M2
      antagonists might be applicable to the pathophysiological study of disease
      states, such as cardiomyopathies.

PMID- 8868292
TI  - Kinetic of in vitro generation of some hemorphins: early release of LVV-hemorphin
      7, precursor of VV-hemorphin-7.
AB  - Bovine globin has been hydrolysed by pepsin to different degrees of hydrolysis.
      Analysis of the hydrolysates, by reversed-phase high-performance liquid
      chromatography (RP-HPLC), shows the release of LVV- and VV-hemorphin-7. LVV
      hemorphin-7 was the first generated, at a degree of hydrolysis (DH), as low as
      4%. In contrast, VV-hemorphin-7 was produced later. Our study clearly shows that
      VV-hemorphin-7 is issued directly from LVV-hemorphin-7, since this later
      completely disappeared during hydrolysis. This work allows us to suggest a
      possible pathway for in vivo hemorphins appearance.

PMID- 8868293
TI  - Inhibitory effect of NPY on the picrotoxin-induced activity in the hippocampus: a
      behavioural and electrophysiological study.
AB  - The effect of neuropeptide Y (NPY) on the picrotoxin-induced activity was studied
      in rat brain hippocampal slices in vitro and after intrahippocampal injection in
      vivo. In the hippocampal slices, NPY (0.1-0.5 microM) inhibited the picrotoxin
      induced epileptiform activity recorded extracellularly in CA1 and CA3 hippocampal
      pyramidal cells. Similar inhibition was induced by the Y2 receptor agonist NPY13
      36, which indicates that the effect of NPY was due to activation of Y2 receptors.
      In behavioural studies, rats with chronically implanted cannulae were injected
      unilaterally into the CA1 hippocampal region with a 1 ml volume of the studied
      substances. Picrotoxin in a dose of 1 mg (1.6 nmol) induced behavioural
      excitation, shakes and weak signs of epileptic behaviour. NPY in a dose of 2 mg
      (470 pmol), but not 1 mg, inhibited some excitatory effects of picrotoxin, but
      did not change the epileptic symptoms. The obtained results suggest that NPY has
      an inhibitory action in the hippocampus, which can be observed in vitro and also
      in a behavioural study.

PMID- 8868294
TI  - A novel [125I]iodinated carboxypeptidase A substrate detects a metallopeptidase
      activity distinct from carboxypeptidase A in brain.
AB  - We have designed two radioactive substrates, hippuryl-L-[3H]phenylalanine and 3
      (p-hydroxy, m-[125I]phenyl)propionic acid ([125I]Bolton reagent) derivative of L
      arginyl-L-phenylalanine, i.e. [125I]BRF, for a highly sensitive assay of
      carboxypeptidase A (CPA) activity. After cleavage of the C-terminal phenylalanine
      residue by CPA, the radioactive product of the reaction was conveniently
      separated by polystyrene bead chromatography. Using [125I]BRF, typical CPA
      activity inhibited by 1 microM 2-benzyl-3-mercaptopropanoic acid was detected in
      extracts from rat pancreas or intestine. In brain and some other tissues,
      however, [125I]BRF-hydrolyzing activity was only inhibited by this compound in
      1000-fold higher concentration, suggesting the participation of a
      metallopeptidase distinct from CPA.

PMID- 8868295
TI  - Further investigations on the effects of neuropeptide Y on the secretion and
      growth of rat adrenal zona glomerulosa.
AB  - NPY is a regulatory peptide, high levels of which are contained in adrenal glands
      of several mammals and which is co-released with catecholamines during various
      stressful conditions. The acute and chronic effects of NPY on adrenocortical
      secretion and growth were studied in the rat. NPY concentration-dependently
      increased aldosterone (ALDO), but not corticosterone (B) secretion of adrenal
      slices (maximal effective concentration was 10(-7) M). Two competitive inhibitors
      of NPY receptors, named PYX-1 and PYX-2, were found to dose-dependently inhibit
      ALDO response of adrenal preparations to 10(-7) M NPY; PYX-2 was more efficient
      than PYX-1, and at a concentration of 10(-5) M completely annulled the effect of
      10(-7) M NPY. The acute bolus intraperitoneal (i.p.) injection of NPY (3 nmol/kg)
      raised plasma ALDO concentration (PAC), but not that of B (PBC); this effect of
      NPY was blocked by the simultaneous injection of PYX-2 (300 nmol/kg). The
      prolonged i.p. infusion with NPY (3 nmol/kg/h for 7 days) increased PAC (but not
      PBC) and induced a marked hypertrophy of the zona glomerulosa (ZG) and its
      parenchymal cells; dispersed ZG cells obtained from NPY-infused rats displayed a
      significantly enhanced basal and maximally agonist-stimulated ALDO production.
      The simultaneous infusion with PYX-2 (300 nmol/kg/h) completely annulled all
      these effects of NPY. The acute or chronic administration of PYX-2 alone did not
      evoke any apparent effect on the ZG secretion and growth. In light of these
      findings the following conclusions can be drawn: (i) NPY is able to stimulate not
      only the secretion, but also the growth of adrenal ZG in rats, via a receptor
      mediated mechanism (since this effect is blocked by PYX-2); (ii) endogenous NPY
      does not play a prominent role in the physiological maintenance of secretion and
      growth of rat ZG (since PYX-2 alone is ineffective); (iii) NPY may play a crucial
      role in the fine tuning of the ZG functions in conditions requiring an increased
      release of mineralocorticoid hormones.

PMID- 8868296
TI  - Chronic naloxone-induced supersensitivity affects neither tolerance to nor
      physical dependence on morphine at hypothalamus-pituitary-adrenocortical axis.
AB  - This study reports the endocrine effects of chronic mu-blockade induced by
      naloxone on morphine tolerance and withdrawal at hypothalamus-pituitary
      adrenocortical (HPA) axis level. Naloxone (0.5 mg/kg/h) or vehicle (1
      microliter/h) were infused s.c. to Sprague-Dawley rats via osmotic minipumps for
      7 days, concomitantly with morphine or placebo pellets for 7-8 days. In opiate
      naive rats, the mu-preferring opioid agonist morphine (30 mg/kg) increased plasma
      corticosterone in a partial but significant naloxone-reversible manner. In
      vehicle-perfused rats, chronic morphine treatment produced tolerance to its
      neuroendocrine effect, while the development of morphine tolerance was
      antagonized in the naloxone-treated group. An enhancement of plasma
      corticosterone levels after acute morphine (30 mg/kg) occurred 24 h after removal
      of chronic naloxone treatment in vehicle-perfused rats, as a functional index of
      supersensitivity to the neuroendocrine effects of the mu agonist. By contrast, 24
      h after naloxone removal, rats implanted with morphine pellets were significantly
      less sensitive to acute morphine (tolerance) than its control-placebo group.
      Substantial elevation of plasma corticosterone, accompanied by motor and
      behavioural signs, was observed after acute naloxone injection (1 mg/kg) to
      tolerant rats 24 h after naloxone-pumps removal, which indicates withdrawal. No
      endocrine, motor or behavioural signs appeared in the naloxone group with pumps
      in place. These results indicated that morphine desensitizes mu-opioid receptors
      that were probably upregulated by chronic naloxone in presence of chronic agonist
      administration, and suggest that opioid tolerance/dependence as well as opioid
      supersensitivity simultaneously and independently can occur at mu-opioid
      receptors mediating HPA function.

PMID- 8868297
TI  - A model for experimentally induced temperomandibular joint arthritis in rats:
      effects of carrageenan on neuropeptide-like immunoreactivity.
AB  - Substance P(SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)-
      and neuropeptide Y (NPY)-like immunoreactivity (-LI) was studied in rats'
      cerebrospinal fluid (CSF), plasma and perfusates (PF) from the temporomandibular
      joints (TMJs) at 2, 6 and 24 h following 0.01 ml injection of 2% carrageenan
      (CAR) into the right TMJ. SP-, NKA-, CGRP- and NPY-LI were significantly
      increased in both TMJ perfusates of the treated groups compared to controls.
      Generally an injection with CAR into the right TMJ induced a similar influence of
      the concentration of SP-, NKA-, CGRP- and NPY-LI in the CSF, plasma and PF at 2,
      6 and 24 h following injection. However, the most pronounced changes in
      neuropeptide-LI occurred intra-articularly in the joint fluid, which indicates
      that both the sensory and sympathetic nervous system are activated in this joint
      following osteoarthritis induction by carrageenan.

PMID- 8868298
TI  - The reduction of preprotachykinin mRNA in the methamphetamine-induced behavioral
      sensitization.
AB  - To study the role of the preprotachykinin A (PPT) mRNA in methamphetamine (MAP)
      induced behavioral sensitization, rats were daily injected within MAP (3 or 6
      mg/kg, i.p., once a day) or saline for 14 days. Progressive enhancement was
      observed in MAP-induced stereotyped behavior. After 7 or 14 days of
      discontinuation of MAP treatment, the rats were decapitated and the brains were
      prepared for Northern blot analysis using a 32P-labeled oligonucleotide probe.
      Northern blot analysis revealed that the level of PPT mRNA in the striatum of 3
      or 6 mg/kg MAP-treated rats was significantly decreased, compared to that in the
      saline-treated controls. These findings indicate that PPT mRNA expression plays
      an important role in MAP-induced long-lasting behavioral sensitization and
      dopamine hyperactivity.

PMID- 8868299
TI  - Endogenous neuropeptides in patients with acute traumatic head injury, I:
      cerebrospinal fluid beta-endorphin levels are increased within 24 hours following
      the trauma.
AB  - The changes in the cerebrospinal fluid (CSF) beta-endorphin (beta-end) levels
      within 24 h following the trauma were examined in 45 patients with head injuries.
      CSF samples obtained from 25 healthy subjects who had minor surgical operations
      under spinal anaesthesia were included as the controls. Patients with head
      injuries were evaluated according to their Glasgow Coma Scale (GCS) scores on
      admission to the neurosurgery clinic and four subgroups were formed as follows:
      Group I: minor head trauma (GCS: 13-15) without skull fracture; Group II: mild
      head injury (GCS: 13-15) with skull fracture; Group III: moderate head injury
      (GCS: 8-12) and Group IV: severe head injury (GCS: < 8). All patients with head
      injury had significantly higher CSF beta-end levels than the controls (P <
      0.001). The levels in patients with mild head injury (Group II) were
      significantly higher than those with severe head trauma (Group IV) (P < 0.001).
      There was not any correlation between the CSF beta-end changes and the GCS scores
      of the patients. Endogenous opioid peptides are suggested to have a role in
      central nervous system (CNS) injuries. However, the CSF levels of beta-end in
      patients with varying degrees of head trauma have not yet been clearly documented
      in the literature. In the present study, significant changes in CSF beta-end
      levels are detected in patients with a wide range of head trauma (from minor head
      trauma to severe injury); however, the increased CSF beta-end levels were not
      correlated to the early prognosis of the patients.

PMID- 8868300
TI  - Localization of immunoreactive endothelin in the neuroendocrine cells of fish
      gill.
AB  - Immunohistochemical tests have demonstrated for the first time the presence of
      endothelins in the neuroendocrine cells of fish gill. We have sought co
      localization of endothelins with serotonin and neuropeptides which are regarded
      as neuroendocrine markers of pulmonary diffuse neuroendocrine systems in higher
      vertebrates. Regarding their endocrine and paracrine activities in mammals,
      endothelins are considered as peptide hormones and growth factors regulating
      respiratory function. The roles of endothelins in the gill await investigation
      based on the multifunctional organization of this organ.

PMID- 8868301
TI  - Effect of receptor blockers on brain natriuretic peptide and C-type natriuretic
      peptide caused anxiolytic state in rats.
AB  - Effect of different doses of centrally administered brain natriuretic peptide
      (BNP) and C-type natriuretic peptide (CNP) were examined in rats with respect to
      anxiolytic properties in an elevated plus-maze model. BNP in doses of 100, 200
      and 400 ng, and CNP in doses of 100 and 200 ng abolished the normal preference
      for the closed arms of the maze, and increased the percentage time spent in the
      open arms; this is consistent with an 'anxiolytic-like' effect. Doses of 50 and
      1000 ng BNP, and of 25, 50, 400 and 1000 ng CNP produced no behavioural effects
      in the elevated plus-maze model. Pretreatment with an alpha-adrenoreceptor
      antagonist or a muscarinergic cholinergic blocker, antagonized the effect of 200
      ng BNP in the elevated plus-maze test. The 'anxiolytic-like' effects of a BNP
      were not modulated by a dopaminergic blocker, an alpha-adrenoreceptor antagonist,
      a GABA receptor antagonist, a 5-HT receptor antagonist or an opiate antagonist.
      The 'anxiolytic-like' effect of CNP was prevented by a dopamine receptor
      antagonist, or an alpha- or beta-adrenoreceptor blocker but not by a
      muscarinergic cholinergic blocker, a GABA receptor, a 5-HT receptor antagonist or
      an opiate receptor antagonist. These results suggest that multiple
      neurotransmitter system activation might be responsible for the BNP and CNP
      induced 'anxiolytic-like' activity.

PMID- 8868302
TI  - Inhibitory effect of intrahippocampal NPY injection on amphetamine-induced
      behavioural activity.
AB  - The aim of the present study was to investigate the influence of intrahippocampal
      neuropeptide Y (NPY) administration on the rats' behaviour. The CA1 field or
      dentate area (GD) of the dorsal hippocampus was chronically implanted with
      intracerebral cannulae. NPY (or redistilled water in the control group) was
      injected bilaterally or unilaterally in a volume of 1 microliter to each
      hippocampus, in a dose of 1 or 2 micrograms per rat. A separate group of rats was
      pretreated with amphetamine (1 mg/kg, s.c.), 15 min before a bilateral
      microinjection of NPY (2 micrograms) into the CA1 region. Immediately after the
      intrahippocampal injection, the rats' behaviour was tested in an open field box.
      It was found that NPY did not change the locomotor and the exploratory activity
      after either CA1 or GD administration to non-pretreated animals. In amphetamine
      pretreated rats, NPY injected into the CA1 field inhibited the amphetamine
      induced increase in sniffing and rearing and, to a lesser extent, the number of
      line-crossings. The obtained results may suggest an inhibitory action of NPY in
      the CA1 hippocampal field on the behavioural hyperactivity.

PMID- 8868303
TI  - Probing the V1a vasopressin receptor binding site with pyroglutamate-substituted
      linear antagonists.
AB  - We have synthesized eight analogues of the linear vasopressin antagonist
      DTyr(Et)2-Phe3-Gln4-Asn5-Arg6-Pro7-Arg8-Tyr(NH2)9 substituted with L-, or D-,
      pyroglutamate at position-1, Asn or Val at position-4 and Arg or Met at position
      6. All of these peptides bound to the V1a vasopressin receptor with affinities
      ranging 33.6-5, 470 nM. Of this series, only two peptides,
      [LpGlu1Val4Arg6Tyr(NH2)9]AVP Kd = 48.4 nM and [DpGlu1Val4Arg6Tyr(NH2)9]AVP Kd =
      691 nM, bound to the V2 vasopressin receptor. All of the neurohypophysial hormone
      receptors studied (V1a VPR, V2 VPR and OTR) were found to be stereoselective with
      respect to the N-terminal pGlu residue. The effect on binding characteristics of
      L-pGlu1 and D-pGlu1 analogues was dependent on both the sequence of the peptide
      and on the receptor subtype in question. From these data we found that peptide 5,
      which has the structure DpGlu-DTyr(Et)-Phe-Val-Asn-Arg-Pro-ARg-Tyr(NH2),
      exhibited the highest V1a/OTR selectivity reported to date (V1aVPR Kd = 82 nM;
      OTR no binding at 10 microM). As such, peptide 5 will provide useful leads to the
      development of ligands with enhanced V1a/OTR selectivity. The binding affinity
      and hydrophobicity of pyroglutamate-substituted peptides was compared with
      previously characterized V1a receptor antagonists which contained a range of
      position-1 substitutions. The hydrophobicity of both cyclic and linear
      antagonists was markedly increased relative to the agonists AVP and [Phe2Orn8]VT
      but increased hydrophobicity alone did not exclusively lead to high affinity
      antagonists. Data presented support the contention that in addition to a general
      increase in hydrophobicity/lipophilicity, position-1 influences the pharmacophore
      of vasopressin antagonists by providing molecular determinants for
      ligand/receptor interaction.

PMID- 8868304
TI  - Dopamine inhibits in vitro release of VIP and proliferation of VIP-immunoreactive
      pituitary cells.
AB  - A double immunohistochemical study for VIP and proliferating cell nuclear antigen
      (PCNA) was carried out on monolayer cultures from adult male rats pituitary
      glands treated with dopamine (ranging from 10(-9) to 10(-5) M), in order to
      establish whether or not dopamine is involved in the regulation of the
      proliferation rate of pituitary VIP-immunoreactive cells. For all doses of
      dopamine assayed, the release of VIP to the culture medium, the numerical density
      of VIP-immunoreactive cells and the percentages of VIP- and PCNA-immunoreactive
      cells decreased significantly after dopamine treatment. These results suggest
      that dopamine could be a physiological inhibitor involved in the modulation of
      pituitary VIP proliferation rate.

PMID- 8868305
TI  - Luteinizing hormone-releasing hormone in undifferentiated and differentiated SK-N
      SH human neuroblastoma cells.
AB  - The presence of luteinizing hormone-releasing hormone (LHRH) in SK-N-SH human
      neuroblastoma cells was investigated by immunocytochemistry and enzyme-linked
      immunosorbent assays of whole cell extracts and culture medium. In addition,
      ribonuclease protection assays were utilized to quantitate LHRH messenger RNA.
      The expression of LHRH mRNA and LHRH protein level was correlated with neuronal
      differentiation induced by retinoic acid (RA). In differentiated SK-N-SH cells
      the LHRH mRNA level as well as the amount of LHRH in cell extracts and cell
      medium were significantly lower than in differentiated cells. These results
      suggest that RA affects the expression of LHRH mRNA and the level of LHRH protein
      in SK-N-SH cells. These data show that altering the growth state of the human
      neuroblastoma SK-N-SH cells toward more neuronal phenotype results in a
      significant decrease in expression of LHRH mRNA and the protein. The ability of
      RA to induce changes in LHRH at the mRNA and at the peptide levels will allow
      further study of RA regulation of LHRH at the neuronal level.

PMID- 8868306
TI  - Determination of the amino acid sequence of the moult-inhibiting hormone from the
      edible crab, Cancer pagurus.
AB  - Putative moult-inhibiting hormone (MIH) from sinus glands of the edible crab
      Cancer pagurus was characterized by high-performance liquid chromatography,
      followed by fractional bioassay (inhibition of ecdysteroid synthesis by Y-organs)
      and immunoassay (using antisera raised against Carcinus MIH). This peptide was
      fully sequenced by automated Edman degradation of endoproteinase-derived
      fragments. C. pagurus MIH is a 78 residue peptide (M(r) 9194), with free N- and C
      termini and three intrachain disulphide bridges. Comparison with previously
      published MIH sequences confirms a high degree of sequence identity (c. 80%),
      supporting the view that brachyurans (crabs), possess distinct, structurally
      similar MIH neuropeptides.

PMID- 8868307
TI  - Dopaminergic regulation of postnatal development of dynorphin neurons in rat
      striatum.
AB  - This study examined whether the postnatal development of the biosynthesis of an
      opioid peptide, dynorphin A (1-8) (DYN) is influenced by dopamine (DA)
      deficiency. The neurotoxin 6-hydroxydopamine (6-OHDA) was used as a tool to
      induce DA deficiency on the third day of the postnatal period in Sprague-Dawley
      rat pups. During the postnatal period, the levels of striatal DYN steadily
      increased in an age-dependent fashion and appeared to peak between 35 and 45
      days. In neonatal 6-OHDA-lesioned animals, the category with 95% or more DA loss
      exhibited a reduction in the levels of DYN in the postnatal period whereas the
      category with less than 95% DA loss did not show significant changes in DYN
      levels. The results indicate that the normal development of striatal DYN is
      negatively affected only when there is a near-total loss of DA during early
      postnatal period.

PMID- 8868308
TI  - Correlation between guanine nucleotide effect and reversible binding property of
      endothelin analogs.
AB  - [125I]-IRL-1620 and [125I]-ET-1 (readily reversible and essentially irreversible
      endothelin (ET) receptor agonists, respectively) were used to demonstrate the
      relationship between the reversible binding nature of ET receptor agonists and
      guanine nucleotide effect using ETB receptors as the model system. Addition of
      increasing concentrations of GTP gamma s to membranes prepared from Chinese
      hamster ovary (CHO) cells stably transfected with human ETB receptors, dog lung
      and pig lung decreased [125I]-IRL-1620 binding to these membranes between 50% and
      60%, whereas [125I]-ET-1 binding to these receptors was unaffected by GTP gamma
      s. Saturation binding experiments in the absence and presence of 100 microM GTP
      gamma s indicated that the apparent dissociation constant [Kd(apparent)] for
      [125I]-IRL-1620 was increased 2 to 2.4-fold in all 3 membrane preparations in the
      presence of GTP gamma s compared to its absence. There was no difference in the
      apparent dissociation constants of [125I]-ET-1 in the presence and absence of GTP
      gamma s in these membrane preparations. This inhibitory effect was specific for
      guanosine triphosphate since adenine nucleotides failed to decrease the affinity
      of [125I]-IRL-1620 for the receptors. The correlation between guanine nucleotide
      effect and reversible binding property of the agonist was further strengthened by
      the observation that in rat cerebellum and rat renal papilla, where [125I]-IRL
      1620 binding was irreversible, guanine nucleotides had no effect on the binding
      of this ligand. These data clearly indicate that there is a good correlation
      between the reversible binding property of the ET receptor agonist and the
      guanine nucleotide effect on the binding of the agonist.

PMID- 8868309
TI  - Monthly bibliography on neuropeptides.

PMID- 8868310
TI  - Paracrine/autocrine regulation of pancreatic islet cell proliferation and
      differentiation in the hamster: studies using parabiosis.
AB  - Partial obstruction of the pancreatic duct in hamsters leads to new islet
      formation and reversal of streptozotocin diabetes. The purpose of this study was
      to delineate the mechanism by which endocrine cell proliferation and
      differentiation is mediated in this model. Six pairs of parabiotic hamsters were
      established and partial duct obstruction was inducted in 1 parabiont from each
      pair. At 6 weeks, the pancreatic weight (mg/100g bw); DNA (microgram/100g bw) and
      protein content (mg/100g bw) showed 28% (167 +/- 21 vs. 130 +/- 17), 32% (1,052
      +/- 206 vs. 795 +/- 159), and 20% (25.4 +/- 6.6 vs. 21.2 +/- 1.9) increases (p <
      0.05), respectively, over the non-wrapped parabionts. Morphometric analysis
      demonstrated the presence of new islets in the wrapped pancreata with a 100%
      increase in the number of islets/mm2 compared with non-wrapped controls (0.90 +/-
      0.5 vs. 1.8 +/- 0.7, p < 0.01). A cytosol extract was prepared from duct
      obstructed pancreases, and 4 microliters/g bw injected i.p. twice daily for 2 d
      produced significant increases in pancreatic weight and DNA content of 12% and
      40%, respectively. Cytosol extract from non-wrapped pancreata had no effects
      compared with saline. When wrapped cytosol extract was injected for 21 d, the
      labeling index of ductular and islet cells (% cell nuclei labeled with 3H-TdR)
      was increased 10- and 6-fold respectively over controls (2.42 +/- 0.28 vs. 0.23
      +/- 0.01 and 1.17 +/- 0.01 vs. 0.25 +/- 0.04, respectively, p < 0.01). The
      trophic effects observed in this model of islet cell proliferation and
      differentiation did not appear to be mediated by a humoral mechanism because the
      changes induced by partial obstruction were not observed in the non-operated
      parabiont. Control of pancreatic endocrine cell growth in this model appears to
      involve paracrine and/or autocrine regulatory mechanisms.

PMID- 8868311
TI  - Plasma and urinary digitalis-like substance levels during atrial natriuretic
      peptide infusion in essential hypertensive patients.
AB  - In order to evaluate the effect of atrial natriuretic peptide (ANP) infusion on
      plasma and urinary digitalis-like substance (DLS) levels, 18 essential
      hypertensive males (mean age 45.6 +/- 3.8 y) were studied. After 1 week on a
      normal NaCl intake (120 mmol/24h), patients were randomly double-blindly assigned
      to receive either ANP (99-126) (0.3 microgram/kg/min) (number of patients = 10)
      or its vehicle (50 ml isotonic saline) (8 patients) over a period of 60 min, in
      supine position. Plasma and urinary DLS levels were measured at time -60, 0, 30,
      60, 120, 180, and 240 min (infusion time from 0-60 min). During ANP infusion,
      plasma DLS levels decreased significantly (from 25.2 +/- 6.8 pg/ml at time 0 to
      12.5 +/- 5.6 pg/ml at 60 min, p < 0.01), while urinary DLS excretion increased
      (from 60.5 +/- 26.1 pg/ml at time 0 to 246.3 +/- 34.2 pg/ml at 30 min, p <
      0.0001). and 402.3 +/- 44.1 pg/ml at 60 min, p < 0.0001). After 3 h from the end
      of ANP infusion, both plasma and urinary DLS returned to baseline levels (20.5 +/
      14.4 pg/ml and 84.5 +/- 34.2 pg/ml, respectively). Taken together, our data show
      that ANP infusion significantly increases urinary DLS excretion, while decreasing
      its circulating levels. This phenomenon could explain the different response of
      ANP and DLS to some stimuli, such as acute volume expansion. In fact, the rapid
      increment of plasma ANP due to an acute increase of extracellular fluid volume
      might simultaneously inhibit the increase in circulating DLS levels by promoting
      the urinary excretion of this substance.

PMID- 8868312
TI  - Determinants of prolonged oral cecal transit time during late phase pregnancy.
AB  - We examined the course of delayed oral cecal transit time (OCTT) and the impact
      of different variables in late pregnancy. Thirty-three women in late trimester
      were evaluated and 29 were re-tested post partum. Results were compared with 17
      controls. A breath hydrogen test was used to measure OCTT. The impact of 3
      demographic and 5 biochemical parameters was evaluated. Oral cecal transit time
      (99.2 +/- 7.8 min) during pregnancy was significantly prolonged compared both
      with controls (63.5 +/- 8.7 min) (p = 0.0042) and post partum (68.5 +/- 6.4 min)
      (p < 0.002). However, 40% during pregnancy had a normal OCTT. Post partum, 8
      (29.6%) continued to have delayed OCTT. Serum free T4 levels were significantly
      lower than in controls (p < 0.0001) and post partum (p < 0.001), but did not
      correlate with OCTT. Gravidity rank correlated with OCTT (p = 0.022). By
      multivariate analysis, only 17% of the observed variability during pregnancy
      could be explained by these parameters. In controls, a formula including
      progesterone and gastrin levels was significant in explaining 54.7% of
      variability. Application of both formulae to post-partum returnees overpredicted
      OCTT; however, the one from pregnancy was more accurate. We conclude that in
      pregnancy multiple factors account for delayed OCTT and these may be different
      from controls and post partum. Pregnancy may still influence OCTT post partum.

PMID- 8868313
TI  - Concurrent utilization review and inappropriate hospital stay: evaluation of a
      program.
AB  - Using a crossover design, we tested the hypothesis that concurrent utilization
      review by a utilization officer would reduce length of stay and inappropriate bed
      days in a tertiary care hospital. The intervention groups included 396
      consecutive patients admitted to specified services during two 1-month study
      periods and followed for at least 1 month or until discharge. Controls were 410
      patients admitted to the same services during a preceding or subsequent month,
      separated by a 1-month washout period. Intervention cases had daily review of
      their care plan and medical condition by the utilization officer to identify
      existing or likely inappropriate hospital stay. The officer used
      interdisciplinary and interdepartmental consultation in attempting to resolve
      identified problems. A separate research nurse identified the controls and
      gathered data on the medical condition and care plan for a random 50% sample of
      both intervention and control cases. These data were used by a multidisciplinary
      panel to count and classify the reasons for inappropriate hospital days. Overall,
      there were no significant differences between the corresponding intervention and
      control groups for length of stay or proportion of inappropriate days. There was
      evidence of a time-related reduction in both length of stay and inappropriate
      days only in the subgroup of patients with a length of stay of < 15 d. As further
      evidence of this period effect unrelated to the intervention, length of stay had
      been declining for 1 of the groups of services before this study began. We
      concluded that concurrent utilization review, as practiced in this study, was
      ineffective in the short term. However, utilization review and modification of
      hospital processes can reduce inefficiency, as evidenced by the time-related
      reduction in inefficiency illustrated in our study.

PMID- 8868314
TI  - Standardized gentamicin dosing enhances peak serum concentrations.
AB  - The objectives of this study were to determine if a standardized gentamicin
      dosing protocol would improve clinical effectiveness, yield higher peak serum
      concentrations, and improve the success rate of attaining peaks in the desired
      range when compared with empiric dosing practices used by prescribers. The study
      was conducted as a before-after program effectiveness evaluation in non
      critically ill patients, aged 16-65 y with stable renal function, who were
      prescribed gentamicin. A standardized dose of 2 mg/kg (ideal or adjusted weight)
      was administered intravenously every 12 h in the intervention phase. Response to
      therapy (time to defervescence, white cell count, reinstitution of antibiotic
      therapy), serum concentrations (peaks > 10 mumol/L (5.6 mg/L) and troughs < 4
      mumol/L (2.2 mg/L)), and toxicity were monitored in both groups. Thirty-four
      consecutive patients were enrolled into the control phase and an equal number
      into the intervention phase. Surgical patients comprised the majority of the
      study population. Desired peak concentrations were attained in 97% of
      intervention vs. 59% of control patients (p < 0.001). Mean peak serum
      concentrations were higher in the intervention phase than in the control phase,
      16.1 mumol/L vs. 11.2 mumol/L (p < 0.001), respectively. Median time to become
      afebrile trended toward a statistical decrease in the intervention as compared to
      the control group, 3 vs. 5 d (p = 0.076), respectively. There was no significant
      difference in clinical effectiveness nor in the occurrence of nephro- or
      ototoxicity. Continued evaluation of this dosing protocol is warranted.

PMID- 8868315
TI  - Increased use of cardiovascular medications in seniors prescribed non-ASA non
      steroidal anti-inflammatory drugs.
AB  - The objective of this study was to determine the relationship between the
      prescribing of non-ASA non-steroidal anti-inflammatory drugs (NANSAID) and the
      prescribing of select cardiovascular (CV) medications. We performed a
      retrospective, cross-sectional analysis of the prescribed use of these
      medications between December 1, 1990 and June 30, 1991 by Albertans 65 years of
      age and older utilizing data from the publically-funded drug benefit plan.
      Variables examined were: the number of individuals prescribed NANSAID and CV
      medications; mean daily dose for these medications; calculated relative dose; the
      proportion of NANSAID users prescribed CV medications compared to non-users; and
      the relative proportions of users of specific NANSAID prescribed CV medication.
      We found that 33.4% and 19.6% of Albertan seniors were prescribed CV medications
      and NANSAID, respectively. NANSAID users were twice as likely to be prescribed CV
      medications as compared to non-users. Intermediate/high dose NANSAID users were
      more likely to be prescribed a CV medication as compared to low-dose users. The
      risk of being prescribed a CV medication was highest for indomethacin and users
      of multiple NANSAID, while ibuprofen users had the lowest risk. We conclude that
      NANSAID users are more likely to be also prescribed CV medications. Subjects who
      consume a lower dose of NANSAID are less likely to be prescribed CV medications.
      For different NANSAID, there is a spectrum of risk.

PMID- 8868316
TI  - [The history of the treatment for portal hypertension].
AB  - Until recently, the only effective treatment for bleeding esophageal varices was
      surgery, including portal-systemic shunts, nonshunting operations, and selective
      shunts. New operations were developed from the neccessity to find a better
      therapeutic modality for the treatment. This article describes the history of
      development of surgical treatment for portal hypertension as well as introducing
      the outline of several such procedures. The history of nonoperative treatments,
      especially endoscopic injection screlotherapy, is also described: Endoscopic
      sclerotherapy as a treatment for bleeding esophageal varices had been employed
      before many definitive surgical procedures. In accordance with the development of
      fiberoptic endoscopy, endoscopic sclerotherapy came into prominance. The less
      invasive treatment is appreciated and popularized even among surgeons today, who
      once believed that shunt operation (or nonshunting operation) was the best
      modality of treatment for esophageal varices. Finally, this article provides
      readers with a simplified guide to Japanese participation in the development of
      treatment for esophagogastric varices.

PMID- 8868317
TI  - [Etiology and hemodynamics of esophago-gastric varices].
AB  - The hemodynamics of the portal area, particularly of the left gastric vein in
      cases of esophago-gastric varices with portal hypertension have revealed that
      only one-third are featuring hepatofugal collateral flow (Type I), while
      hepatopetal and/or to and fro flow (Type II) forms make up about two-thirds.
      Furthermore, regarding the supply of blood to the varices, in all cases a
      contribution of arterial blood inflowing through the left gastric artery to the
      upper part of the stomach was found. Therefore, concerning the etiology of
      varices other than that due to hepatofugal collaterales, a hyperdynamic state of
      the upper part of the stomach area has been considered as an important factor.
      With regard to the micro-circulation of the gastric wall, it was proved that the
      hyperdynamic state was caused by an increase in submucosal arterio-venous
      anastomoses, and this was concluded to be directly responsible for the etiology
      of the varices. Therefore, the appropriate therapeutic approach to varices should
      as the rule be based on interruption both of hepatofugal collaterales and
      arterial flow, or the drainage of the hypertensive state of the local venous
      system.

PMID- 8868318
TI  - [The pathogenesis of idiopathic portal hypertension].
AB  - Idiopathic portal hypertension (IPH), so called Banti's disease, is characterized
      by anemia, splenomegaly and portal hypertension. While sharing certain clinical
      features, IPH is distinct from liver cirrhosis not only in histopathology and
      natural history but also in vascular anatomy and portal hemodynamics. Our studies
      have shown that the majority of patients with IPH have high serum levels of
      immunoglobulins, including autoantibodies, associated with abnormally high
      frequencies of activated T cells and the biased usage of particular T cell
      receptor (TCR) V beta gene segments. These results suggested that IPH was an
      immunological disorder mediated by a continuous stimulation with either a certain
      antigen or more likely a superantigen.

PMID- 8868319
TI  - [Recent progress in the diagnosis of gastroesophageal varices].
AB  - Recent advances in the diagnosis of gastroesophageal varices are reviewed in this
      paper. Endoscopy, angiography, ultrasound, and ultrasound Doppler are now
      employed in the diagnosis of varices. As for endoscopic diagnosis, new criteria
      for the evaluation of gastroesophageal varices have been applied. Angiography is
      now not only used to demonstrate the varices and collateral circulations in
      portal hypertension but also used in the embolization therapy for large gastric
      varices or intractable esophageal varices. Ultrasound and color Doppler are now
      widely used in the diagnosis of portal hypertension because of its
      noninvasiveness and conveniency. Furthermore, in its use in endoscopy, varical
      vessels and blood flow in the wall of the esophagus and the stomach can be
      directly demonstrated. Recent advances in these diagnostic modalities will made
      it possible to diagnose gastroesophageal varices and evaluate the pathophysiology
      in patients with portal hypertension more precisely.

PMID- 8868320
TI  - [Preventive treatment of gastroesophageal varices].

PMID- 8868321
TI  - [Endoscopic sclerotherapy for gastroesophageal varices].

PMID- 8868322
TI  - [Present status of endoscopic therapy for esophageal varices--endoscopic variceal
      ligation (EVL)].
AB  - Recently, EVL was developed to provide the endoscopist a safer method for the
      treatment of esophageal varices. The purpose of this report is to reveal our data
      and the present status. From 1989 to 1995, we performed EVL with EIS using
      Aethoxysklerol in a total of 214 patients who had bleeding and/or risky
      esophageal varices. Our technique of EVL is as follows; For prophylactic and
      elective patients, a spiral ligation method was employed and followed by EIS to
      obtain the complete eradication. When active bleeding was observed, direct
      ligation was performed onto the bleeding point and if the bleeding point was not
      found, spiral ligation method was done. Eradicating effect was observed in 97% of
      the entire patients and 29 active/spurting bleedings were well controlled by this
      technique. Complications were experienced in 12 cases (2 stenosis and 10 post EVL
      ulcedr bleeding), however, there were no patients who could not be managed by
      endoscopic treatment. Variceal recurrence after EVL/EIS were occurred in 36 of
      214 patients (16.8%). Recurrent period was ranged from 1 month to 24 months and
      mean period was 10 months. We conclude that EVL/EIS is safe, easy and effective
      mean for the treatment of esophageal varices.

PMID- 8868323
TI  - [Non-decompression surgery for esophagogastric varices--indication and
      postoperative result of esophageal transection with paraesophagogastric
      devascularization and Hassab procedure].
AB  - A total of 548 patients had an non-decompression surgery for esophagogastric
      varices in our hospital, from September 1979 to August 1995. Type of operation
      includes 402 cases of esophageal transection with paraesophagogastric
      devascularization (via thoracic approach). 40 cases via abdominal approach, and
      106 cases of Hassab procedure. The origin was cirrhosis in 454 patients, IPH in
      46, extrahepatic portal occlusion in 29, primary biliary cirrhosis in 6, Budd
      Chiari syndrome in 4 and others in 9. Operative mortality rate was less than 1%
      in child A group, although overall mortality rate including child B, C was 5.0%.
      By thoracic approach, residual esophageal varices were observed only in 2.5%.
      Postoperative variceal recurrence were appeared high in cases with hepatocellular
      carcinoma (HCC). Cumulative recurrence rates at 15 years after surgery were
      20.2%, unless HCC had occurred. Cumulative survival rates at 10, 15 years were
      52.1%, 45.6% respectively in liver cirrhosis without HCC. Present study confirmed
      that our operation is effective in controlling esophagogastric varices in long
      term of periods. Esophagogastric varices of IPH, EHO, and liver cirrhosis of
      Child A group should be treated by non-decompression surgery.

PMID- 8868324
TI  - [Selective shunt surgery for the treatment of portal hypertension].

PMID- 8868325
TI  - [Interventional radiology for portal hypertension. PTO.TIO].
AB  - Percutaneous transhepatic obliteration (PTO) and transileocolic vein obliteration
      (TIO) are techniques of interventional radiology for embolization of collaterals
      due to portal hypertension 1) We can obtain good results from the precise
      selection of these techniques in accordance with the patient's hemodynamics and
      general condition. 2) Endoscopic injection sclerotherapy (EIS) combined with PTO
      or TIO for esophageal varices proves to be superior in reliability and durability
      to EIS alone, and the time before retreatment is much longer when this
      combination therapy is used. 3) In the intractable EIS only cases, a distinct
      improvement in results and prognosis appears in using PTO or TIO and also in
      adding more EIS thereafter. 4) After treatment with EIS and PTO or TIO for
      cardiac varices, we obtain better results in the disappearance rate as well as in
      the recurrence rate compared with EIS alone. 5) Gastric varices disappear and
      hepatic encephalopathy due to porto-systemic shunt is improved after PTO or TIO
      or using these with balloon occluded retrograde transvenous obliteration (BRTO).
      Thus PTO and TIO would be analogous to surgical devascularization or ligation.
      Therefore it is concluded that the best results would be obtained with PTO or TIO
      with other nonsurgical treatments.

PMID- 8868326
TI  - [Balloon-occluded retrograde transvenous obliteration for treatment of
      gastroesophageal varices].

PMID- 8868327
TI  - [Transjugular intrahepatic portosystemic shunt: a new therapy for portal
      hypertension].
AB  - Thirty-five patients with portal hypertension due to liver cirrhosis secondary to
      chronic viral hepatitis underwent transjuglar intrahepatic portosystemic shunt
      for the last 3-year period. Shunts were successfully completed in 31 of 35
      patients at 89%. Portal vein pressure was markedly reduced on average in the all
      cases until 6 months after TIPS. The endoscopic findings of varices much improved
      in 90% of the patients. Long-term patency rates of TIPS were 97% after 4 weeks,
      79% after 6 months, 76% after a year and 55% after 2 years, respectively. The
      authors concluded that TIPS was an effective and reliable means of lowering
      portal pressure, improving endoscopic findings of varices and controlling of
      refractory ascites.

PMID- 8868328
TI  - [Drug therapy for the treatment of portal hypertension].

PMID- 8868329
TI  - [Contradiction in health care economics].

PMID- 8868330
TI  - [Action myoclonus, intention tremor and terminal oscillation].

PMID- 8868331
TI  - [Skeletal myoclonus and midbrain tremor].

PMID- 8868332
TI  - [Concepts and pathophysiology of dystonia].

PMID- 8868333
TI  - [The alien hand sign].

PMID- 8868334
TI  - [Right hemispheric dominancy in the auditory evoked magnetic fields for pure-tone
      stimuli].
AB  - It is well known that the auditory evoked N100m response is dominant in the
      contralateral hemisphere to the stimulated ear: N100m latency is shorter and
      N100m amplitude is larger in the contralateral hemisphere than the ipsilateral
      hemisphere. Interhemispheric asymmetry of the N100m responses were reported in
      terms of the equivalent dipole localization: the right hemispheric N100m dipole
      is more anterior to the left hemispheric dipole. In the present study, we
      investigated interhemispheric asymmetry of the auditory evoked P50m and N100m
      response in terms of signal amplitude. A helmet-shaped whole head
      magnetoencephalography system was employed to see small but significant
      differences between two hemispheres. Thirty-seven right-handed healthy subjects,
      31 males and 6 females, participated in the study. The helmet-shaped whole head
      MEG system (CTF Systems-Osaka Gas) consists of an array of 66 MEG sensor sites
      uniformly distributed over the entire head. The monaural auditory stimuli, 2000
      Hz tone burst of 50 msec duration were delivered to the left and then the right
      ear sequentially, with an intensity of 80 dB SPL at the ear. White noise of 50 dB
      SPL was delivered to the opposite ear. The inter-stimulus intervals were
      randomized in the range from 2.5 to 4.7 sec. In a total of 37 subjects, N100m
      dipole pattern appeared on both hemispheres either left or right ear stimuli.
      When P50m peak amplitude was compared between contralateral responses, the right
      hemispheric response (141.5 +/- 16.3 fT, mean +/- s.e.m.) was slightly larger
      than the left-hemispheric response (134.3 +/- 10.2 fT). Differences, however,
      were not significant. When P50m peak amplitude was compared between ipsilateral
      responses, the right-hemispheric response (135.1 +/- 11.0 fT) was slightly larger
      than the left-hemispheric response (115.3 +/- 10.9 fT). Differences were not
      significant, either. When N100m peak amplitude was compared between contralateral
      responses, the right-hemispheric response (484.4 +/- 28.4 fT) was statistically
      (p < 0.01) larger than the left-hemispheric response (375.6 +/- 28.0 fT). When
      N100m peak amplitude was compared between ipsilateral responses, the right
      hemispheric response (405.8 +/- 27.9 fT) was statistically (p < 0.02) larger than
      the left-hemispheric response (315.1 +/- 24.8 fT). Previously, we reported that
      the right hemispheric latency is shorter than the left hemispheric latency in the
      auditory evoked field N100m responses. Present study indicated another evidence
      of the right hemispheric dominancy in the auditory evoked responses, namely the
      lager amplitude in the right hemispheric response at least for pure-tone stimuli.
      The whole-head MEG system is suitable to analyze differences of auditory function
      between two hemispheres.

PMID- 8868335
TI  - [A clinico-pathological study of cystic spinal Schwannomas].
AB  - It is not rare for a spinal Schwannoma to have cystic formations, but there are
      various opinions about the mechanism. Since the installation of MRI in our
      institution in 1989, we have experienced 4 cases of cystic spinal Schwannoma. The
      diagnosis of such lesions was based on identifying cystic formations
      histopathologically. Among these cases, tiny hemorrhages were noted
      microscopically in three of them along with hemosiderin depositions and
      phagocytes containing hemosiderin. Besides, there are also a lot of sinusoidal
      vessels with thin endothelium. Perhaps in these three cases, it is the tiny
      hemorrhages that resulted in degenerative changes which in turn caused the
      formation of microcysts. But in addition to the above findings, a lot of
      hyalinized vessels were also demonstrated in the angiomatous components of two
      cases. Therefore, it is also possible that the microcyst formation is secondary
      to the degenerative changes caused by ischemia within the tumors. On the other
      hand, in the only case without hemorrhage, neither phagocytes containing
      hemosiderin nor abnormal sinusoidal vessels could be found. In stead, a lot of
      clear foamy cells with positive lipid staining were seen. There may be some
      factors underlying the xanthomatous change of these tumors that cause their
      vacuolar formation from degenerated of the foamy cells. It is possible that all
      three factors mentioned above may act alone or in combination to contribute to
      the formation of cysts. At its late stage, a spinal Schwannoma may have various
      findings which can not be classified into either Antoni A or Antoni B type. In
      conclusion, a spinal Schwannoma can occasionally have cystic formations. Its
      mechanisms can be a hemorrhagic or an ischemic process occurring within the
      tumor.

PMID- 8868336
TI  - [Corticobasal degeneration and progressive supranuclear palsy--differentiation by
      somatosensory-evoked potentials].
AB  - It is by no means easy to make an early differential diagnosis between
      corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), because
      both disorders occasionally show similar clinical features such as parkinsonism,
      supranuclear gaze palsy, or dementia. In the present study, we studied
      somatosensory-evoked potentials (SEPs) in 4 CBD and 8 PSP patients. SEPs after
      median nerve stimulation (0.2 ms square wave delivered with a frequency of 1 Hz)
      were recorded from bilateral parietal and midfrontal electrodes. Latencies of
      identifiable peaks and the inter-peak amplitudes were measured, and a comparison
      was made between the two disorders. Both latencies and amplitudes of all the
      identified peaks showed no statistical difference between the two disorders. To
      reveal an inter-hemispheric difference of the amplitude, we calculated the
      asymmetry index: the amplitude of the more affected side/the sum of the
      amplitudes of both sides. In CBD patients, an asymmetry index of P1N2 amplitude
      was found to be decreased significantly. The asymmetric appearance of this part
      of SEPs may be helpful for early differential diagnosis between CBD and PSP.

PMID- 8868337
TI  - [Excitatory amino acids and prostanoids release in spinal cord injury].
AB  - Acute spinal cord trauma may initiate a cascade of hemodynamic and biochemical
      events characterized by direct mechanical destruction of neurons, hemorrhages and
      significant increases in active substances (glutamate, prostaglandins (PGs),
      ets.). However, there are no data which define the effect of acute spinal cord
      trauma on biochemical changes in the spinal cord. The aim of the present study
      was to examine time-dependent biochemical changes in the spinal cord by
      intrathecal microdialysis in the acute stage of spinal cord turama. METHODS: Male
      Sprague-Dawley rats (300-325g) were implanted with a dialysis catheter and PE-10
      catheter in the intrathecal space of the lumbar spinal cord. Three days later the
      animals were anesthetized with halothane and 10-min dialysis samples were
      collected. Compression spinal cord injury was produced by inflating an extradural
      2F-Fogarty balloon catheter (L4-L5) for 60 sec. After compression, samples were
      collected while the animals remained anesthetized for 30 min, and additional
      samples were collected until 4hr post-injury. At the end of the dialysis period
      neurological function was briefly evaluated. Microdialysate samples were analyzed
      for glutamate, aspartate, and taurine by HPLC-UV and for PGE2 by RIA. RESULTS:
      Compression of the spinal cord caused significant increases in the levels of all
      amino acids. The greatest in creases were in glutamate and aspartate at 10 min,
      followed by a decrease over the rest of the 4-hr period. Similarly, PGE2 showed
      an immediate increase after compression, with normalization between 1-2 hr, but
      this was followed by a secondary increase at 2-4 hr. Neurologically, all animals
      displayed complete paralysis with loss of sensory function that remained
      unchanged for the 4-hr period. COMMENT: The present study clearly demonstrated
      the time course of spinal amino acids and PGE2 release by using a chronically
      implanted dialysis catheter after spinal cord compression and also showed a
      correlation with neurological deterioration. These biochemical changes in the
      extracellular space may display various, multiphasic patterns reflecting
      progressively developing edema and corresponding ischemia.

PMID- 8868338
TI  - [Surgical case of cerebral pilocytic astrocytoma--clinicopathologic study and
      analysis of proliferation potential by PCNA staining].
AB  - The clinical and the pathological features of a surgical case of adult pilocytic
      astrocytoma in the right temporal lobe are described. The growth kinetics of the
      tumor cells were investigated by immunohistochemical staining of Proliferating
      cell nuclear antigen (PCNA). The patient, a 23-year-old man, was admitted to our
      hospital with a history of loss of consciousness. A CT scan showed a cystic
      lesion with enhanced mural nodule in the right temporal lobe. Total resection of
      the mural nodule including the surrounding cyst wall was performed.
      Histopathological examination revealed tumor cells exhibiting a biphasic pattern
      with capillary proliferation and some Rosenthal fibers. Only 8.7% of the tumor
      cells were PCNA-positive. Pilocytic astrocytoma of the cerebrum is a clearly
      recognizable, distinctive entity with a natural history and pathological features
      similar to those of the relatively benign cerebellar astrocytoma of childhood.
      Standardized assessment of PCNA in pilocytic astrocytomas of the cerebrum may be
      useful as an independent indicator of biological behavior.

PMID- 8868339
TI  - [A case of alveolar soft-part sarcoma with cerebral metastases].
AB  - A case of alveolar soft-part sarcoma with multiple cerebral metastases in
      addition to multiple lung and bone metastases is reported. This is a rare tumor
      which thus far has only been recognized as a malignant soft tissue tumor with
      great uncertainty. A 24-year-old man with a chief complaint of left frontal
      headache was admitted to our unit on September 26, 1994. A tumor of the right
      forearm had been surgically removed 9 years previously, and surgery had been
      followed by two courses of chemotherapy with vincristine, cyclophosphamide and
      actinomycin-D and subsequent irradiation for bone metastasis. The chemotherapy,
      however, did not have any clear effect. Neurological examination at the time
      revealed only bilateral papilledema, but CT and MRI scan of the brain showed a
      round mass in the left occipital lobe with homogeneous enhancement and another
      small mass was detected in the right occipital lobe. A cerebral angiogram showed
      a vascular tumor. The preoperative diagnosis was multiple cerebral metastases of
      alveolar soft part sarcoma. Left occipital craniotomy was performed on October
      12, 1994, and the tumor was completely removed by lobectomy. Specimens of the
      tumor showed typical histological features of alveolar soft-part sarcoma. Whole
      brain radiotherapy was administered postoperatively, and the patient is well
      neurologically without right homonymous hemianopsia. The clinical features of
      alveolar soft-part sarcoma are discussed. Only a few cases have been reported in
      the literature, but the most frequent site of the primary lesion has been the
      lower extremities, and cerebral metastasis has not been rare. All efforts should
      be focused on discovering this tumor in the early stage because surgical removal
      can yield good results, and radiotherapy is thought to be effective in terms of
      patient "quality of life".

PMID- 8868341
TI  - [Cerebellopontine angle epithelial cyst presenting as hemifacial spasm].
AB  - A rare case of cerebellopontine angle epithelial cyst presenting as hemifacial
      spasm is reported. The patient was a 35-year-old man with right hemifacial spasm
      of 2 months duration. A preoperative CT scan showed a well-demarcated low density
      area in the right cerebellopontine angle. The cyst was totally excised under an
      operating microscope. The postoperative course was uneventful, and the right
      hemifacial spasm resolved immediately. Histologically, the cyst wall was composed
      of a stratified epithelial lining composed of non-ciliated cuboidal or squamous
      cells. Ultrastructurally, the epithelial layer consisted of two types of cells:
      non-ciliated cells with microvilli coated with electron-dense material, and
      basally located cells with tonofilaments and well-developed desmosomes. The
      latter type of cells appear identical to the basal cells characteristically seen
      in the upper respiratory tract and the gastrointestinal tract. This findings
      suggest that the cyst was of endodermal origin rather than neuroectodermal
      origin.

PMID- 8868340
TI  - [Somatoparaphrenia caused by the lesion in the dominant cerebral hemisphere--a
      case report].
AB  - We reported a rare case of cerebral infarction with somatoparaphrenia (SP) caused
      by involvement of the dominant cerebral hemisphere. The patient was 77-year-old
      right-handed woman who was noted to have atrial fibrillation, right hemiplegia,
      hemisensory disturbance and ipsilateral homonymous hemianopsia.
      Neuropsychologically, there were anosognosia (AG) for hemiplegia and SP arguing
      her hand as doctor's hand. In addition, there also were noted disorientation,
      right unilateral spatial neglect and mild amnestic aphasia. Brain CT and MRI
      demonstrated infarctions in the left lateral thalamus, internal capsule, lateral
      geniculate body, hippocampus, caudate nucleus and medial occipitotemporal gyrus.
      IMP-SPECT showed extensive hypoperfusion areas in the left cerebral hemisphere.
      These lesions were thought to have resulted from occlusion of the left anterior
      choroidal artery and partial occlusion of the left middle and posterior cerebral
      arteries caused by cardiogenic embolism. AG persisted and SP disappeared 80 days
      after the onset. While AG and SP are generally believed to be associated with non
      dominant hemispherical lesion, the present case suggests the possibility that
      those symptoms were seen in the case of dominant hemispherical lesion without
      severe aphasia.

PMID- 8868343
TI  - Current status of CF gene therapy.

PMID- 8868342
TI  - [A 63-year-old woman with muscle weakness, myotonia, and parkinsonism].
AB  - We report a 63-year-old woman who presented myotonia and parkinsonism. The
      patient was well until 15 years of the age when she noted that the ring finger of
      her left hand at times flexed when she did not intend to do so. She noted
      weakness in her left upper extremity at the age of 40, and difficulty in relaxing
      her hand grip at 45. She had an onset of tremor in her right foot at age 50,
      which was followed by difficulty in gait and hand writing. She was admitted to
      Juntendo University Urayasu Hospital when she was 63-year-old. Her mother, two
      sisters, and a son were affected with similar muscle weakness and myotonia.
      Although some of them developed stooped posture in the late stage of the disease,
      none of them had overt parkinsonism. General physical examination was
      unremarkable. Neurologic examination revealed an alert and oriented woman with
      some recent memory loss. She had bilateral ptosis, facial weakness, and a masked
      face. Myerson's sign was present. Her speech was small and monotonous. The
      sternocleidomastoid muscles were markedly atrophic and weak. The remaining of the
      cranial nerves were intact. She walked in small steps with freezing with support.
      She showed bradykinesia, retropulsion, and resting tremor in her right leg.
      Slight distal dominant weakness was noted in both upper and lower extremities
      more on the left. No cerebellar signs were noted. Muscle stretch reflexes were
      within normal limits in the upper extremities and diminished in the lower limbs.
      Sensation was intact. Routine laboratory findings were unremarkable. Cranial CT
      scan and MRI revealed slight cortical atrophy and leukoaraiosis. She responded to
      levodopa and she became able to walk by herself. She was transferred to another
      hospital one month after her admission. She had several bouts of airway
      obstruction with one episode of respiratory arrest. She expired six month after
      the transfer. The patient was discussed in a neurological CPC, and the chief
      discussant arrived at the conclusion that this patient suffered from myotonic
      dystrophy and Parkinson's disease which set in later years. Postmortem
      examination on the iliopsoas muscle revealed uneven muscle fiber diameters,
      central nuclei, and type 1 fiber predominance; the pathologic finding was
      consistent with myotonic dystrophy. The substantia nigra showed marked cell loss
      and Lewy bodies in the remaining neurons. The finding was consistent with
      Parkinson's disease. In myelin stain, diffuse myelin pallor was noted in the
      cerebral white matter which was the pathologic substrate of leukoaraiosis in this
      patient. Combination of these two disorders have never been reported in the
      literature to our knowledge. It appears to be that the coincidence is just a by
      chance phenomenon, but it seems interesting to note that accelerated aging
      process appears to be present in both myotonic dystrophy and Parkinson's disease.

PMID- 8868344
TI  - Making of a Schwann.

PMID- 8868345
TI  - Simple modifications to increase specificity of the 5' RACE procedure.

PMID- 8868346
TI  - Pattern formation in the immortal Hydra.
AB  - Well-documented experimental studies with Hydra, done 10-20 years before Mozart
      was born, marked the dawn of modern developmental biology. Since those days, the
      immortal and perpetually embryonic hydra has been a classic model system, but
      despite its deceptively simple appearance, hydra has not yielded its secrets
      readily. Recent evidence points to a pivotal role of PI-PKC-type signal
      transduction pathways in morphogenesis: interference with these pathways results
      in polyps with multiple heads or feet. While molecular techniques are revealing
      genes involved in pattern realization, a new model of pattern regulation, based
      on competition for hormonal factors by autoregulatory receptors, emphasizes
      epigenetic interactions.

PMID- 8868347
TI  - Protein aspartate phosphatases control the output of two-component signal
      transduction systems.
AB  - Phosphorylation or dephosphorylation of an aspartate regulates the output
      activity of the response regulator of two-component signaling systems. Signal
      input in these systems is dependent on signal-transducing kinases, which can
      respond to a variety of signal ligands and, in some cases, to small
      phosphorylated metabolic intermediates. The kinase component of many two
      component signaling systems also displays a response regulator-phosphate
      phosphatase activity that inactivates the response regulator in response to
      signals. Newly discovered kinase-independent phosphatases allow additional
      signals to influence the extent of response-regulator phosphorylation. Such
      phosphatases are prevalent in signal transduction systems controlling complex
      processes, such as the initiation of development in microorganisms.

PMID- 8868348
TI  - Regulated synthesis, transport and assembly of the Drosophila germ plasm.
AB  - Germ cells are set aside during early development and, in many organisms
      (including Drosophila melanogaster, Caenorhabditis elegans and Xenopus laevis),
      they form in a unique cytoplasm, termed the germ plasm. The germ plasm is
      synthesized during oogenesis, and the initial polarization of the oocyte is
      likely to determine where the germ plasm will form within the egg cell. Although
      we do not know how the fate of germ cells is specified in any organism, recent
      genetic analysis in Drosophila has identified the TGF-alpha homolog gurken as the
      signal involved in the initial polarization of the oocyte. These results imply
      that the limiting steps in the assembly of the germ plasm are localization of the
      OSK RNA and regulated synthesis of the OSK protein, encoded by oskar, which are
      components of the germ plasm.

PMID- 8868349
TI  - DNA chips: analysing sequence by hybridization to oligonucleotides on a large
      scale.
AB  - Complete sequences of genomes and comprehensive sets of cDNA sequences open the
      way to a hugh range of biological problems. There is a need for analytical
      methods that can deal with the large number of sequences in the data banks and,
      ideally, we would like to analyse all sequences together. Gel-based sequencing is
      a serial process that analyses one sequence at a time. Oligonucleotide arrays, or
      'DNA chips', are miniature, parallel analytical devices, which could bring to
      sequence analysis and molecular genetics many of the advantages that
      semiconductor devices brought to computing.

PMID- 8868350
TI  - Management of large bile duct stones.

PMID- 8868351
TI  - Endoscopic management of large bile duct stones by mechanical lithotripsy.
AB  - OBJECTIVE: Our experience in treating large common bile duct stones using Olympus
      basket mechanical lithotripter (BML 2Q) and Soehendra lithotripter is reported.
      METHODS: Between July 1990 and December 1993, twenty two patients with common
      bile duct stones too large to be extracted by Dormia basket or balloon were
      treated with BML lithotripter or Soehendra lithotripter. RESULTS: The stone
      diameters ranged from 1.5 to 2.8 cm. Fourteen patients required one session of
      lithotripsy, four patients two sessions each, and two patients three sessions
      each. BML lithotripter was used in 14 patients. In the remaining eight patients
      the stones were fragmented with Soehendra lithotripter when the basket got
      impacted while attempting extraction. Mechanical lithotripsy was successful in 20
      patients (91%). Indwelling stent was used in one patient; one patient underwent
      surgery. CONCLUSION: Mechanical lithotripsy is safe for the treatment of large
      common bile duct stones, with a success rate above ninety percent.

PMID- 8868352
TI  - Correlation of manometric and radiographic diagnosis in esophageal motility
      disorders.
AB  - BACKGROUND: Radiography and manometry are complementary investigations in the
      diagnosis of esophageal motility disorders. In most centers, however, manometry
      is not available and diagnosis is based on radiography alone. AIMS: To correlate
      the findings on radiography in patients with esophageal motility disorders in
      whom a manometric diagnosis was available. METHODS: Retrospective analysis of
      esophageal manometry and barium contrast studies of 138 patients, done for
      suspected motility disorders, over a period of two years. RESULTS: Manometry was
      abnormal in 111 (80.4%) cases [achalasia 87, scleroderma 6, non specific
      esophageal motility disorders (NEMD) 13, diffuse esophageal spasm (DES) 5].
      Radiology was abnormal in 106 cases; the overall radiographic sensitivity was
      73.9% (achalasia 87.4%, scleroderma 83.3%, NEMD 38.5%) and the positive
      predictive value was 75.5% (achalasia 95%, scleroderma 100%, NEMD 29.4%).
      CONCLUSION: Radiography has a high sensitivity and positive predictive value in
      esophageal motility disorders like achalasia and scleroderma but in DES and NEMD
      the two investigative modalities (radiography and manometry) do not correlate
      well.

PMID- 8868353
TI  - Isolation and characterization of Helicobacter pylori strains from peptic ulcer
      patients in Dhaka, Bangladesh.
AB  - To study the association of Helicobacter pylori with peptic ulcer and the
      associated histopathological changes, to characterize the isolated strains in
      terms of their protein profile, 83 peptic ulcer cases were studied. A high
      association of H pylori with peptic ulcer (duodenal ulcer 77%, gastric ulcer 75%)
      and gastritis (74%) was observed. Age and smoking did not have any relationship
      with H pylori infection. The infection was predominantly associated with the
      'quiescent' form of chronic gastritis. Comparative sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of whole cell extracts of the local isolates
      and a reference strain from Australia showed a general homogeneity between the
      strains with obvious interstrain differences. However, the difference between the
      local isolates and the reference strain was more marked. Significant association
      of H. pylori with peptic ulcer along with strain variations were observed.

PMID- 8868354
TI  - Total and segmental colonic transit time in non ulcer dyspepsia.
AB  - BACKGROUND: Patients with non ulcer dyspepsia (NUD) often have associated lower
      alimentary tract symptoms which are labelled as due to the irritable bowel
      syndrome. AIMS: To asymptomatic colonic dysmotility is present in patients with
      NUD. METHODS: We studied total and segmental colonic transit times in 25 patients
      with NUD (14 men age range 20-70 yr), and 25 matched normal controls (13 men; 18
      50 yr), using the multiple-marker, single-film technique. Twenty markers each
      were administered at 0, 9 and 18 h and an abdominal film taken at 27 h. RESULTS:
      Total colonic transit time was shorter (median 9 h) in patients with NUD as
      compared to controls (median 15.8 h) p = 0.0018, with similar segmental motility
      pattern as in controls. There was no significant difference between the symptom
      subgroups of NUD. CONCLUSIONS: Patients with NUD often have altered colonic
      transit even in the absence of symptoms. NUD may therefore be only a subset of
      diffuse gastrointestinal dysmotility with predominant proximal alimentary tract
      symptoms, whereas the term irritable bowel syndrome is used when lower tract
      symptoms predominate.

PMID- 8868355
TI  - Gastric bacterial overgrowth accompanies profound acid suppression.
AB  - BACKGROUND: Suppression of gastric acid may lead to gastric colonization by
      aerobic and anaerobic bacteria, and consequent clinical manifestations. The risk
      is likely to be higher with poor environmental hygiene. AIMS: To study the effect
      of short-term acid suppression with omeprazole on gastric bacterial flora.
      METHODS: Twenty-five ambulatory patients with acid-peptic diseases underwent
      clinical assessment and gastric juice collection (for pH and culture) prior to
      start of therapy with 20 mg omeprazole daily, on days 7 and 14 of therapy, and 7
      days after omission of therapy (day 21). RESULTS: Eighteen patients completed the
      study. The median gastric pH was 1.8, 7.5, 7.5 and 3.4 on days 0, 7, 14 and 21
      respectively. Positive gastric cultures were obtained in 13 of 25, 17 of 21, 18
      of 18 and 14 of 18 patients on respective study days, with median colony counts
      of 1.5 x 10(4), 7.5 x 10(5), 8.7 x 10(7) and 7.3 x 10(4) cfu/mL respectively.
      Three patients developed self-limiting diarrhea during therapy and two more
      immediately after discontinuing therapy. CONCLUSIONS: Gastric colonization is
      common with short-term profound acid-suppression, and may cause diarrhea. Acid
      suppressive therapy should be used with caution especially in patients with poor
      environmental hygiene.

PMID- 8868356
TI  - Effect of a short course of indomethacin on gastric mucosal blood flow using
      endoscopic laser-Doppler velocimetry.
AB  - OBJECTIVE: To assess the effect of a short course of indomethacin on gastric
      mucosal blood flow (GMBF). METHODS: Patients with musculo-skeletal pain of recent
      origin and were prescribed a short course of therapy with indomethacin (25 mg tid
      for 7 days) were studied Baseline measurements of GMBF were carried out using
      endoscopic laser-Doppler velocimetry prior to starting indomethacin. At sites on
      the antrum, incisura, lesser and greater curvatures, and fundus. GMBF
      measurements were repeated after indomethacin therapy, as above and also on sites
      of erosions, it any. RESULTS: Baseline GMBF at sites on the antrum, incisura,
      greater and lesser curvatures, and fundus were (mean) 8.6, 7.9, 8.8, 8.5 and 8.7
      volts, respectively. Post-therapy values did not differ from the corresponding
      baseline values (8.7, 8.5, 8.6, 8.6 and 8.3 volts, respectively). However, ten of
      the 16 patients developed gastric mucosal erosions and the mean GMBF on these
      sites of erosion was significantly reduced (6.6 +/- 1.3 volts, p < 0.05).
      CONCLUSIONS: A short course of indomethacin therapy produces a patchy decrease in
      blood flow in the gastric mucosa and erosions were seen in these areas.

PMID- 8868357
TI  - Helicobacter pylori in the Indian environment.

PMID- 8868358
TI  - Pancreatico-pleural fistula: successful treatment with octreotide.
AB  - A patient with chronic pancreatitis who presented with massive pleural effusion
      due to pancreatico-pleural fistula is reported. Treatment with octreotide for
      three weeks healed the fistula and resolved the pleural effusion.

PMID- 8868359
TI  - Carcinoid tumor presenting as acute abdomen due to hemoperitoneum.
AB  - A patient presenting with massive hemoperitoneum due to a large retroperitoneal
      carcinoid tumor is reported.

PMID- 8868360
TI  - Role of hepatobiliary scintigraphy in management of postoperative bile leak into
      the lesser sac.
AB  - A case with bile leak into the lesser sac of peritoneum is reported. Although
      bile leak following biliary surgery or trauma is not uncommon, isolated bile leak
      into the lesser sac is rare. This information may be vital for appropriate
      placement of the drainage tube in the abdomen. A hepatobiliary study, as
      reflected in this report, is extremely useful in guiding the surgeon in this
      respect.

PMID- 8868361
TI  - Helicobacter pylori gastritis masquerading as gastric lymphoma.
AB  - A 30-year-old man presented with acute acid-peptic symptoms. Endoscopy and
      radiological studies revealed generalized thickening of gastric folds with
      multiple superficial ulcerations and infiltration of the distal stomach
      simulating gastric neoplasm. Endoscopic biopsies revealed acute gastritis with
      foveolar hypertrophy with numerous Helicobacter pylori. The symptoms and
      endoscopy findings resolved completely with combination triple-drug therapy for H
      pylori.

PMID- 8868362
TI  - Congenital jejunal leiomyoma in a neonate.
AB  - Leiomyomas of the small intestine are rare in neonates. We report a neonate with
      jejunal leiomyoma, who presented with acute intestinal obstruction.

PMID- 8868363
TI  - Detection of hepatitis C virus by third generation enzyme immunoassay.

PMID- 8868364
TI  - Cecocutaneous fistula forty years after appendicectomy.

PMID- 8868365
TI  - Rare Ryle's tube knot.

PMID- 8868366
TI  - Factors of Ehrlich Ascites Tumor resistance to oxidative stress.
AB  - Ehrlich Ascites Tumor (EAT) cells, compared to liver, were less susceptible to
      peroxidation (measured by the TBARS method) induced by Fe2+/ascorbate, ADP/Fe2+
      and H2O2/Fe2+/ascorbate. Higher thiobarbituric acid reagent products TBARS levels
      were found with Fe2+/ascorbate or after ultrasonication induced peroxidation in
      lipids obtained from Ehrlich cells compared to EAT cell homogenate with the same
      lipid content. This suggests that non-lipid and structurally membrane
      antioxidants factors are of less importance for induction by Fe2+/ascorbate than
      by ultrasonication. The resistance to induced lipid peroxidation (LPO) in EAT
      cells is associated with the lower level of lipids, the lower double-bond index,
      the lower level of fatty acids reacting with TBA, as well as with the relatively
      higher level of alpha-tocopherol per mg lipid in the EAT cells as compared to the
      liver.

PMID- 8868367
TI  - beta-Adrenoceptor agonists-induced desensitization in rat trachea.
AB  - The development and the characteristics of beta-adrenoceptor agonists-induced
      desensitization in rat trachea were studied. Tracheal strips were contracted with
      carbachol and cumulative concentration-response curves for various beta
      adrenoceptor agonists were constructed before and after 30-min incubation either
      with the same beta-adrenoceptor agonist or with another beta-adrenoceptor
      agonist. Some problems of the in vitro desensitization in rat trachea were also
      considered.

PMID- 8868368
TI  - Effect of lesions to the supramammillary area of the posterior hypothalamus on
      atrial natriuretic peptide release following acute blood volume expansion in
      conscious Wistar rats.
AB  - Acute blood volume expansion (AVE) is a potent stimulus for atrial natriuretic
      peptide (ANP) release. Since several central nervous structures are well known
      for their involvement in the regulation of fluid and electrolyte homeostasis and
      in the secretion of central ANP, we carried our experiments on 33 conscious
      Wistar rats in order to determine if the integrity of the supramammillary (SMA)
      hypothalamic area is essential for the peripheral ANP response to AVE. We
      performed stereotaxic electrolytic lesions of SMA in part of the animals. To
      obtain AVE we administered 2 mL saline/100 g b.m. for 2 minutes into v. jugularis
      through the chronically implanted venous catheters. Plasma ANP was assayed
      radioimmunologically. AVE significantly increased plasma ANP both in the intact
      animals and in the lesioned rats. This concluded that SMA is not involved in the
      regulation of peripheral ANP release during AVE.

PMID- 8868369
TI  - Effects of cholecystokinine on the gallbladder motility: interaction with
      somatostatin and vasoactive intestinal peptide.
AB  - Recent years have seen an increase in the information concerning the mechanisms
      of action of brain-gut neuropeptides (cholecystokinin (CCK), vasoactive
      intestinal peptide (VIP), somatostatin (SS)) on the biliary tract motility. This
      article is intended to extend our knowledge of the problem and based on our
      recent studies. Researchers and students interested in an historical overview of
      the subject, as well as in the information on the physiology and pharmacology of
      biliary smooth muscle are referred to earlier reviews (Ryan, 1981, 1987). The
      article focuses on the involvement of cholinergic mechanisms in the action of
      CCK, SOM and VIP on the gallbladder motility under in vivo and in vitro
      conditions. Some species differences in the responses of the gallbladder to CCK,
      VIP and ACh have also been described. Furthermore, new data about the
      interactions between CCK, SOM and VIP in the regulation of the gallbladder
      motility are presented.

PMID- 8868370
TI  - Effect of verapamil and diltiazem on the rCBF and the rCBF autoregulation in
      cortex and thalamus of cats.
AB  - The effects of Verapamil and Diltiazem, administered at a dose of 0.3 mg/kg i.v.,
      on the autoregulation of the regional cerebral blood flow (rCBF) in the cortex
      and the thalamus were studied on 28 cats. The animals were anesthetized with
      ether and alfa-chloralose. The rCBF was registered by the hydrogen clearance
      method with locally generated hydrogen. The mean arterial blood pressure (MABP)
      elevation was performed by an i.v. infusion of angiotensin (0.2 microgram/min).
      The mean initial values of the cortical rCBF were 71.15 ml/100g/min and of the
      thalamic rCBF -46.85 ml/100 g/min. The mean limits of the cortical rCBF
      autoregulation were: 137.5 mm Hg for the absolute limit (La) and 31.25 mm Hg for
      the relative limit (Lr). The mean limits of the thalamic rCBF autoregulation
      were: 157.75 mm Hg for the (La) and 46.5 mm Hg for the (Lr). Verapamil increased
      the cortical rCBF by 40% and the thalamic rCBF by 24%. The absolute limits of
      rCBF autoregulation were decreased by 22% in the cortex, and by 15% in the
      thalamus. The relative limits were decreased by 31% in the cortex and by 35% in
      the thalamus. Diltiazem increased the cortical rCBF by 42% and the thalamic rCBF
      by 6%. The absolute limits of rCBF autoregulation were decreased by 21% in the
      cortex and the thalamus. The relative limits were decreased by 52% in the cortex,
      and by 38% in the thalamus.

PMID- 8868371
TI  - Pharmacology of tolerance to benzodiazepine receptor ligands.
AB  - State of the art of pharmacology of tolerance to and dependence on benzodiazepine
      receptor ligands is shortly summarized. Firstly, the inadequacies of animal
      models of drug-dependency are underlined. Then, some elements of molecular
      biology of the GABA-A receptor complex are described to give a theoretical
      background for discussing pharmacological profiles of action of the selective
      type 1 (e.g. zolpidem), and partial benzodiazepine receptor agonists (e.g.
      bretazenil). These groups of benzodiazepine receptor ligands are considered to
      exhibit low tolerance and dependence liability. The evidence from behavioral and
      electrophysiological experiments so far favors the concept that the gradually
      developing hypofunction of the brain GABA system is the basis for tolerance to
      benzodiazepines, and the cause of abstinence symptoms. Receptor binding studies
      on adaptive changes in the GABA-A and benzodiazepine receptors after chronic
      benzodiazepine administration, insofar gave negative or contradictory results.
      The available up to now data on the long-term processes occurring in the subunits
      of the GABA-A receptor complex are also not homogenous, and it is difficult to
      discuss them. Likewise, the contribution of neurosteroids and specific ligands of
      the peripheral type of benzodiazepine receptor to the discussed phenomenona, is a
      matter of controversy. In conclusion, it should be stressed that the selective
      type 1 benzodiazepine receptor agonists, and partial benzodiazepine receptor
      agonists, either due to excitation of a smaller fraction of receptors, or lower
      efficacy, do not entirely readjust the function of the GABA-A receptor complex,
      thus leaving the place for action of the endogenous neurotransmitter. Such
      profile of central activity should prevent the development of strong tolerance
      and abstinence symptoms.

PMID- 8868372
TI  - Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.
AB  - GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine]
      has been described as a non-competitive AMPA (non-NMDA glutamate) receptor
      antagonist. In the present paper some behavioral effects of GYKI 52466 were
      studied in male Wistar rats and male Albino Swiss mice. GYKI 52466 reduced the
      locomotor activity in normal rats and mice, without evoking any symptoms of
      behavioral stimulation. The CGP 37849-induced hyperlocomotion was increased by
      GYKI 52466. The akinesia in monoamine-depleted rats was not affected by the drug
      studied. The antiakinetic effect of L-DOPA was not changed by GYKI 52466, whereas
      the antiakinetic effect of L-DOPA+CGP 37849 was decreased. GYKI 52466 increased
      the hyperlocomotion induced by apomorphine or cocaine. The drug did not change
      the catalepsy induced by haloperidol or fluphenazine, as well as the
      anticataleptic effect of CGP 37849. GYKI 52466 was inactive in the forced
      swimming test, but increased the antidepressant effect of CGP 37849. The flexor
      and extensor muscle tone of the rats hind limb was not modified by GYKI 52466.
      The results obtained indicate that GYKI 52466 shows a neuropharmacological
      profile similar but not identical with that of the quinoxalines (competitive AMPA
      receptor antagonists) studied previously.

PMID- 8868373
TI  - Antagonistic effect of MR2266 and MR2267 on morphine or nalbuphine analgesia at
      the spinal levels in rats.
AB  - The aim of this paper was to study the effect of two benzomorphan derivatives
      MR2266 and MR2267 with predominant antagonism to kappa-opioid receptors
      administered intrathecally on the analgesic action of morphine and nalbuphine.
      Both compounds attenuated the analgesia elicited by examined opioid agonists. Our
      results support the hypothesis that the spinal opioid receptors take part in
      analgesic effect of morphine and nalbuphine. It was for the first time described
      that MR2267, considered as inactive enantiomer of MR2266, is an active opioid
      antagonist when administered intrathecally.

PMID- 8868374
TI  - Effect of some anti-cancer drugs and combined chemotherapy on the
      pharmacokinetics of antipyrine in the rat.
AB  - The effect of anti-cancer drugs on the metabolic efficiency of the liver was
      evaluated by means of phenazone (antipyrine) kinetics individually in each rat.
      Chlormethine (nitrogranulogen, NG), methotrexate (MTX), floxuridine
      (fluorouracil, 5-fluorouracil, 5-FU), cyclophosphamide (CY, endoxan), and three
      cytostatics applied jointly (MTX + 5-FU + CY) were administered ip to the rats,
      while antipyrine was given intravenously. The anti-cancer drugs: NG, MTX, 5-FU,
      CY and MTX + 5-FU + CY delayed the elimination of antipyrine. Statistically
      significant prolongation of the half-life, decrease in the elimination rate
      constant and the clearance of antipyrine have been found in the rats receiving
      anti-cancer drugs, as compared to the controls. After the administration of MTX,
      5-FU, CY and the joint administration of MTX + 5-FU + CY the volume of
      distribution did not change, while the volume of distribution of antipyrine
      decreased after the administration of NG. The activity of the investigated
      enzymes, i.e., alanine aminotransferase (ALAT), aspartic aminotransferase
      (AspAT), gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), which are
      the indicators of various liver dysfunctions, did not change after the
      administration of NG, MTX, 5-FU, CY and MTX + 5-FU + CY. The administered
      antineoplastic drugs in mono and polytherapy changed the activity of oxidase
      mixed function responsible for the metabolism of antipyrine. CY administered to
      rats in polytherapy had less influence on liver metabolic efficiency than in
      monotherapy.

PMID- 8868375
TI  - Activity of adenosine deaminase in red blood cells of patients suffering from
      multiple sclerosis treated with adrenocorticotropic hormone.
AB  - Adenosine deaminase (ADA) activity was studied in red blood cells of patients
      suffering from multiple sclerosis treated with adrenocorticotropic hormone
      (ACTH). ADA activity in hemolysates was determined according to the method of
      Hopkinson and calculated as units per g of hemoglobin. Activity of adenosine
      deaminase in healthy subjects was 0.871 +/- 0.251 U/g Hb. In patients with
      multiple sclerosis, before treatment ADA activity was 0.765 +/- 0.131 U/g Hb and
      was about 15.2% lower than in the control group (p < 0.02). After treatment with
      ACTH, ADA activity increased to 1.005 +/- 0.211 U/g Hb (p < 0.001). We have
      suggested that increased activity of adenosine deaminase in red blood cells of
      patients suffering from multiple sclerosis after treatment with ACTH is caused by
      diminution of superoxide generation, and therefore its sparing effect on cell
      membrane and enzyme is connected with membranes.

PMID- 8868376
TI  - Effect of quercetin on the growth of mouse fibroblast cells in vitro.
AB  - The cytotoxic and antiproliferative activity of quercetin was investigated on
      mouse fibroblast cells (NCTC) in vitro. Quercetin caused partial growth
      inhibition when used in the concentration of 10 micrograms/ml and almost complete
      growth inhibition, when it was applied in the concentration of 50 micrograms/ml.
      The decrease of cell proteins content as well as the reduction of mitotic index
      were used as indicators of growth inhibition. Moreover, quercetin influenced the
      course of mitosis in the cell. An increase in the number of cells in telophase as
      well as elevation of the number of giant and multinuclear cells were observed in
      the cultures with quercetin. The effect of quercetin on proliferation of cells
      depended on the concentration and the time of cell exposure to the compound. On
      the basis of these results it can be concluded, that mechanism of quercetin
      action at the cell level is complex. It could be associated with disturbances of
      cell division due to effect of quercetin on proteins, DNA and cytomembranes.

PMID- 8868377
TI  - Rapid down-regulation of beta-adrenergic receptors evoked by combined forced
      swimming test and CGP 37849--a competitive antagonist of NMDA receptors.
AB  - The influence of CGP 37849, a competitive antagonist of NMDA, receptors and
      desipramine (DMI) on the density of beta-adrenergic receptors in rats exposed to
      the forced swimming test was investigated. CGP 37849 (10 mg/kg) and DMI (15
      mg/kg), given twice to rats (24 h apart), or the forced swimming test alone
      failed to alter the density of beta-adrenergic receptors in the rat cortex, as
      tested using [3H]dihydroalprenolol ([3H]DHA). However, in rats injected with CGP
      37849 (10 mg/kg) or DMI (15 mg/kg) and exposed to the forced swimming test, it
      was found that the density of beta-adrenergic receptors in the cortex was
      decreased. It was also observed that CGP 37849 used in a dose which decreased the
      density of beta-adrenergic receptors reduced the immobility time in a manner
      similar to DMI. It is concluded that CGP 37849 may evoke similar adaptive
      receptor changes as anti-depressant drugs which-in turn-suggests antidepressant
      like properties of CGP 37849.

PMID- 8868378
TI  - Histamine-and isoprenaline-evoked stimulation of cAMP formation in chick cerebral
      cortex.
AB  - Histamine (HA) and isoprenaline (ISO) strongly stimulated cAMP formation in chick
      cerebral cortical slices. The effects of HA and ISO were selectively antagonized
      by HA H2-receptor blockers (aminopotentidine, ranitidine) and beta-adrenoceptor
      blocker propranolol, respectively. The combination of HA (0.1-100 microM) and ISO
      (0.1-10 microM) produced some additive effects when the drugs were used at low
      concentrations, i.e. 0.1-1 microM but not when HA was applied at 10 or 100 microM
      doses (which evoked nearly maximal effect). It is suggested that HA H2-like
      receptors and beta-adrenoceptors (whose activation leads to stimulation of cAMP
      formation) are localized in the same subpopulation of cortical cells, in which
      they probably utilize a common and limited pool of cAMP-generating system.

PMID- 8868380
TI  - Trends in HIV-1 and HIV-2 prevalence and risk factors in pregnant women in
      Harare, Zimbabwe.
AB  - The spread of the human immunodeficiency virus (HIV) and the resulting morbidity
      and mortality are major public health challenges with adverse social and economic
      implications. The pregnant population serves as an important marker of the extent
      of the problem in the sexually active low risk categorized population.
      Furthermore, a high HIV prevalence among women of childbearing age contributes to
      neonatal and infant mortality through perinatal transmission and also a large
      number of uninfected children become orphans. The objective of the present study
      was to determine the HIV prevalence rate and the risk factors in pregnant women
      attending antenatal care clinics in the Greater Harare area of Zimbabwe. Women
      presenting for antenatal care in four maternity clinics between May 1994 and June
      1995 were tested for HIV-1 and HIV-2 antibodies following informed consent,
      counselling and completion of a questionnaire. Of the 1.168 women, 30.4 pc tested
      HIV-1 positive, with prevalence rates ranging from 23.6 pc at a lower density
      clinic, 28.6 pc in a medium density clinic, 30.7 pc in a higher density clinic
      and 33.2 pc at the referral maternity hospital. HIV-2 was present in 7.6 pc of
      the women. The 20 to 29 years age group had the highest HIV prevalence of 35 pc,
      (Odds Ratio (OR) = 2.4; 95 pc CI-1.33 to 4.32). Single pregnant women were more
      likely to test positive, (OR = 2.1; 95 pc CI = 1.2 to 3.7). Thirty five pc of the
      women reported previous use of condoms and in those where condom use was reported
      in casual relationships, there was a higher risk of HIV (OR 6.1; 95 pc CI = 2.1
      to 17.3). Reported use of intravaginal herbs was associated with HIV risk (OR
      1.4; 95 pc CI = 1.1 to 1.8; p < 0.03). History of genital ulcer (OR = 2.3),
      discharge (OR = 2.4), rash (OR = 2.7), genital ulcer with PID (OR = 5.8) was
      significantly associated with HIV infection. Present findings indicate a 30.4 pc
      HIV prevalence rate for a sample of 1,168 pregnant women in Harare. This rate is
      much higher than the 18 pc HIV prevalence rate reported for 1,008 pregnant women
      in the same Greater Harare area in 1990. We conclude that there is need for
      further innovative and aggressive community based as well as institutional
      interventions aimed at reducing HIV risk. Prevention strategies should include a
      wide range of socially contextualized initiatives.

PMID- 8868379
TI  - Chlamydial infection in a population of Ethiopian women attending obstetric,
      gynaecological and mother and child health clinics.
AB  - The prevalence of chlamydial infection was assessed in 1,846 Ethiopian women
      attending clinics in Addis Ababa. Sera were tested for type-specific anti
      chlamydial antibodies using purified chlamydial antigens (C. trachomatis A-C (CTA
      C), C. trachomatis D-K (CTD-K), Lymphogranuloma venereum (LGVI-3), and C.
      pneumoniae (CPn), in a micro-immunofluorescence (micro-IF) test. Three levels of
      chlamydial infection were established. Sera with: 1) antibodies to CTA-C, CTD-K,
      LGV 1-3 and CPn singly or in combination, are considered as evidence of overall
      exposure to chlamydial species (OEC); 2) antibodies to CTD-K and LGV 1-3 are
      considered as evidence of exposure to genital chlamydial pathogens (GENCI); 3)
      IgM titre > or = 1/8, or Ig G titre > or = 1/64 to CTD-K and LGV 1-3 alone or at
      a similar level with antibodies to CTA-C and CPn is considered as being evidence
      of active genital chlamydial infection (AGCI). OEC was found in 84 pc, GENCI in
      60 pc and AGCI in 42 pc. Infection was highest in family planning and lowest in
      antenatal clinic attenders. OEC increased progressively with age while GENCI and
      AGCI peaked at ages 35 to 49. Chlamydial infection was highest in those married
      and sexually active < 13 years of age (OEC 88 pc, GENCI 69 pc, AGCI 49 pc); the
      lowest income groups (OEC 85 pc, GENCI 65 pc, AGCI 45 pc); those with more than
      five sexual partners (OEC 92 pc, GENCI 78 pc and AGCI 65 pc); with highest
      prevalence in bargirls (OEC 97 pc, GENCI 84 pc, AGCI 75 pc). Fifty pc had
      clinical evidence of past or present infection in the urethra, salpinges or
      bartholin glands (USB). OEC, GENCI and AGCI were associated with PID. The
      association of seropositivity with USB was remarkably similar for both gonorrhoea
      and chlamydial infection: we recommend adoption of a treatment regimen effective
      for both infections. The micro-IF test is a useful epidemiological tool for
      identifying the of antibodies to chlamydial pathogens. Use of antigen pools CTA
      C, CTD-K LGVI-3 and CPn enables a distinction to be made between genital and non
      genital infections. The problem of symptomatic and asymptomatic chlamydial
      disease needs to be addressed urgently.

PMID- 8868381
TI  - Value for money in South African health care: findings of a review of health
      expenditure and finance.
AB  - This article highlights the most striking findings of a review of health
      expenditure and finance in South Africa in 1992/3. The level of national
      expenditure on health care, and the distribution of resources between the public
      and private sectors, are discussed first. Then the article highlights the
      maldistribution of financial, physical and human resources on a geographic basis,
      racially and between levels of care. The cost of redressing inequities, at least
      at the primary care level, is mentioned in the context of seeking options for
      additional sources of finance. The article concludes by examining the planning
      prerequisites for successful reform.

PMID- 8868382
TI  - Peripartum hysterectomy at Ga-Rankuwa Hospital: a two and a half year review.
AB  - A two and a half year review of 39 peripartum hysterectomies done at Ga-Rankuwa
      Hospital from 1 January 1993 to 30 June 1995 was conducted. There were a total of
      21,108 deliveries, 4,894 (23.19 pc) of which were caesarean deliveries. The ages
      of the patients ranged from 17 to 46 years and parity from 0 to 9. A large
      number, 31 (79.5 pc) of the patients were unbooked. The commonest indications
      were ruptured uterus 14 (35.9 pc) puerperal sepsis 13 (33.3 pc) and post partum
      haemorrhage four (10.3 pc). The complications included wound dihescence, sepsis,
      bladder injury, ureteral injury and two deaths occurred.

PMID- 8868383
TI  - Incidence of Armillifer armillatus (pentastome) calcification in the abdomen.
AB  - Analysis of plain abdominal radiographs in 214 patients showed Armillier
      armillatus calcification in three cases (1.4 pc). Two of these cases were males
      aged 50 and 70 years respectively. The only female with pentastome calcification
      was aged 35 years giving a male to female ratio of 2:1. Typically the
      calcifications were either comma-shaped or rounded with central lucency measuring
      about 5 mm in diameter. Two (66.7 pc) of the three patients who were positive for
      parasitic calcification complained of abdominal pain. This however, does not
      necessarily imply a causal relationship between pentastome infestation and
      abdominal discomfort.

PMID- 8868384
TI  - Urethral mucosa prolapse in young girls.
AB  - Two cases of urethral prolapse in young girls are presented. One patient had
      urethral bleeding and the other presented with acute urinary retention. In
      Tanzania, to the best of our knowledge, urethral prolapse as a cause of acute
      urine retention in girls has not been reported. The management is also discussed.

PMID- 8868385
TI  - [The 60th anniversary of the All-Union Research Institute of Medical Instrument
      Making].

PMID- 8868386
TI  - [The status of and problems in the development of Russian medical instrument
      making].
AB  - Recently, there have been great changes in the nomenclature of manufactured
      medical equipment (ME) items and hence there is a considerable renewal of
      products due to the fact that a lot of conversed enterprises of the military
      industrial complex (MIC) have settled down in producing ME. By and large, the
      output of new ME items is 37% of their total medical instrument making
      nomenclature. Thus, in 1988 the proportion of the items was 35% of the total
      output of medical devices and apparatuses while in 1995 it is 65%. The output and
      technical level of some extremely complex ME items, Russian devices for
      hemodialysis and extracorporeal circulation have been increased. The Russian
      enterprises have designed and are manufacturing diagnostic nuclear magnetic
      systems, pulse oximeters, Billitest bilirubin meters, complex laboratory sets for
      radioimmunochemical assay, a G202-5 lit-par-lit scanning complex, Mammodiagnost
      apparatus, new Roentgen-48 and Roentgen-60 X-ray complexes, etc. The paper gives
      specific examples how a number of medical devices and apparatuses are designed
      and launched into production at the electronic and radio industrial and MIC
      enterprises.

PMID- 8868387
TI  - [The creation and manufacture of anesthetic respiratory equipment based on a
      complex systems approach].
AB  - The systems complex approach is essential for designing and manufacturing
      anesthetic respiratory equipment due to its great medical significance, a wide
      range, complexity, and rigid requirements for reliability. The system in question
      includes the subsystem "apparatus", "patient", and "operator" in each a
      considerable factors considering the existing features of designing, equipping
      the therapeutical institutions, as well as traditions, manufacturing
      characteristics, potential risks, etc. The application of this approach is
      analyzed by using the Spiron-type artificial lung ventilation and Polynarkon-type
      inhalation anesthetic apparatuses as examples.

PMID- 8868388
TI  - [The standardization of equipment for artificial pulmonary ventilation and
      inhalation anesthesia in Russia].
AB  - Basic trends in the standardization of anesthetic and respiratory equipment are
      considered. Its important impact on the functional characteristics, safety, and
      specific features in the manufacture of apparatuses, for artificial lung and
      ventilation anesthesia are stressed. A brief review of the system of standards
      that apply to this important type of medical equipment is given. The need for
      taking into account the international standards which reflect the global practice
      of design and use of anesthetic and respiratory equipment is emphasized. Basic
      difficulties in applying the standards are due to a great number of various
      normative documents, a more strict and frequently formal approach that exists in
      Russia for meeting the specifications, weak effectualness of standards for
      components used in general engineering. Topical tasks to harmonize the
      requirements for standards, to make consideration of the existing features of
      design, production, and use better, and to expand the requirements for the
      functional characteristics of equipment are set.

PMID- 8868389
TI  - [A trial of the clinical use of the Testascan computerized gamma tomograph in
      neurosurgical pathology].
AB  - The paper outlines the diagnostic potentialities of the first Russian
      multidetector Testascan gamma-tomograph. With this, three different radio
      pharmaceuticals (RP) were used; 99mTC-GM PAO for examining cerebral circulatory
      disorders, 99mTC pertechnetate for visualizing tumor foci, and 99mTC-DTPK for
      studying impaired cerebral liquor pathway. Regional cerebral blood supply was
      studied in 78 patients with arterial aneurysms and arteriovenous malformations,
      with stenoses and thromboses of the great arterial trunks, as well in patients
      with brain injury sequelae and hypophyseal, craniofascial, and cavernous sinus
      tumors, VIII-neurinomas, meningiomas of the pyramid of the temporal bone. Some
      103 patients with various intra- and extracerebral volumetric formations are
      examined. The impaired cerebral liquor pathways were explored in 27 patients with
      pathological processes of various genesis. Experience in clinically using the
      Russian Testascan computer gamma-tomograph in neurosurgical care has shown its
      high validity in diagnosing various focal processes of tumor and nontumor
      genesis. Single photon emission computerized tomography (SPECT) may reveal foci
      of abnormal elevation or reduction of RP accumulation by showing different
      anatomically topographic characteristics. SPECT is the most promising in the
      study of cerebrovascular diseases of various genesis and in the presence of
      tumors at basal sites.

PMID- 8868390
TI  - [Conceptual and technological diagnostic problems in the prevention and
      rehabilitation of stroke].
AB  - The paper provides the optimum algorithms for diagnosing the severity of
      prestroke cerebral circulatory disorders and determining the poststroke brain
      lesion extent. It is suggested that various techniques, such as radionuclide
      diagnosis, Doppler ultrasonography, postural disorder correction should be
      employed.

PMID- 8868391
TI  - [Russian electrophysiotherapeutic apparatus. The problems of its design and
      production].
AB  - The topical organizational problems of design, production, and use of
      physiotherapeutical equipment (PTE) are discussed. PTE is considered to be basic
      tools employed in physiotherapy. The therapeutical effect of PTE on man is
      produced by currents of different frequency and shape by means of electrodes
      (which come in contact with a patient's body) or an electromagnetic field having
      different frequency-modulation characteristics via non-contact method by means of
      radiating elements. The devices which transform electromagnetic to mechanical
      energy may be subsumed under a separate group that includes ultrasonic
      therapeutical apparatuses, mechanical massage and mechanical stimulation
      equipment. The leading PTE designer is "VNNIMP-VITA Co. which has developed and
      launched about 20 varying = purpose PTE models into practice. The interest
      displayed by the conversed enterprises of the military industrial complex in the
      manufacture of medical equipment items and primarily PTE has recently caused
      unsystematic development of new PTE which have not been positively assessed and
      introduced into medical practice. New PTE models should be designed by
      strengthening the relations between those who design this type of medical
      equipment and the new structures of the Russian Academy of Medical Sciences.

PMID- 8868392
TI  - [Correction of the breathing in the treatment of bronchial asthma by means of
      biological feedback].
AB  - The development of nondrug therapies for bronchial asthma (BA) is highly
      pressing. The application of respiration-correcting methods and means that
      implement a principle of biological feedback (BFB) is one of the promising lines.
      To polish procedures for practical work and to evaluate their efficiency, a
      respiration corrector has been devised, which visualizes a patient's external
      respiration rhythm and synchronizes it with the reference rhythm whose parameters
      are set by a physician or by a patient himself. The efficiency of BFB technique
      was evaluated in the treatment of BA in children. Studies using the device were
      done 2-3 times a day with 15-20 min in each session. The treatment regime
      averaged a fortnight. Its application relieved the occurred episode without drugs
      in most children with mild and moderate BA, prevented attacks and made them
      fewer, prolonged remission, and reduced the amount of bronchodilatating agents to
      be used. BFB correction made under the polyclinic setting is indicated for
      patients with mild and moderate atopic BA in the episode, postepisode, and
      interepisode periods and contraindicated for patients with severe BA when they
      have an episode. Treating BA via BFB correction diminishes psychosomatic
      disorders: anxiety, bronchodilator dependence, fear of a recurrent episode,
      whining, irritability, and insomnia.

PMID- 8868393
TI  - [The design of a family of ultrasonic diagnostic units based on up-to-date
      computer technologies].
AB  - Small ultrasonic devices are now being used in medical practice. However, the
      vast majority of them represent designingly completed systems which cannot
      include additional soft- and hardwares to accumulate measurements and to set up
      databases, to make additional postprocessing, to transmit measurements along
      networks and telephone lines, etc. On the other hand, in our and foreign
      countries, work is under way in designing the systems of archiving and treating
      ultrasonic images, working places for a physician engaged in radiation diagnosis.
      But at the same time direct joining of ultrasonic equipment with standard
      computer facilities is impossible in many practical cases. To design ultrasonic
      devices by using Multimedia IBM PC technology which may integrate various
      informational media, such as display, sonic information, and textual data is one
      of the ways of solving this problem. With this, the hardwares of ultrasonic
      devices are realized in the construction of standard IBM PC modules. Sonomed
      ultrasonic devices may be considered to be alternatives of Multimedia IBM PC
      based devices.

PMID- 8868394
TI  - [Integrated data processing systems for a functional diagnostic service].
AB  - The paper discusses the problem of automation of the functional diagnostic
      service system on the basis of up-to-date informational technologies, gives
      recommendations on the minimum list of diagnostic procedures used for various
      service levels in medical institutions, outlines requirements for hard- and
      softwares needed for designing this system of integrated processing, provides
      specific recommendations on the structure of automatic complexes for the first
      two levels of functional diagnostic service.

PMID- 8868395
TI  - [Methods and means for the noninvasive assessment of the cerebral circulation].
AB  - The main clinical and diagnostic tasks while studying cerebrovascular diseases
      have been defined and set on the basis of analysis of the biophysical and
      pathophysiological factors and parameters that characterize the cerebral
      circulation in health and disease. The currently available physioengineering
      methods and means for evaluating cebral hemodynamics. Proposals to design new
      equipment and to improve the existing one and recommendations how to use them
      while examining the cerebral circulation in various clinical situations are
      given.

PMID- 8868396
TI  - [Computerized instrumental tools for psychophysiological studies of normal higher
      nervous activity and in pathology].
AB  - The paper considers the theoretical bases of design and examples of practical use
      of specialized computerized instrumental tools for psychophysiological studies of
      higher nervous activity in man. A number of principles in the design of medical
      devices and units for psychophysiological examinations have been defined by
      analysing some P.K. Anokhin's concepts and from the author's own experience in
      designing and employing psychophysiological equipment, which is reflected in the
      concept of psycho-engineering. The paper provides the most typical examples of
      some generations of the proposed scientifically based devices and complexes for
      psychophysiological examinations, such as a KPFK computerized unit for
      psychophysiological examinations, a specialized personal computer terminal for
      determining the characteristics of sensomotor coordination and tremor, a
      specialized physicomedical terminal of a personal computer for evaluating the
      steadiness of the gravity center of a person's position, Rhythmo-Mnemo-Binatest
      automatic microprocessor apparatuses for assessing the characteristics of human
      higher nervous activity in health and in disease.

PMID- 8868397
TI  - Effects of sodium bicarbonate and sodium chloride on the elimination of etorphine
      in equine urine.
AB  - The combination of large doses of sodium bicarbonate and the potent narcotic,
      etorphine, has reportedly been given to racehorses in attempts to improve their
      performance and also to "mask" the presence of etorphine in urine samples. The
      increased urinary output and pH associated with sodium bicarbonate (approximately
      500 g) administration may reduce the urinary concentration of etorphine, making
      it more difficult to detect. Our experiment was designed to examine the effects
      of this combination. Six Thoroughbred horses were used in a latin-square design
      with three horse pairs and three treatments consisting of the following:
      etorphine (20 micrograms), etorphine (20 micrograms) plus sodium bicarbonate (1.0
      g/kg), and etorphine (20 micrograms) plus sodium chloride (0.7 g/kg). Sodium
      chloride was used to distinguish between the urinary alkalinizing effects of
      sodium bicarbonate and the diuretic effects associated with the large electrolyte
      load. Venous blood and urine samples were collected prior to and for 24 h post
      treatment. Sodium bicarbonate produced a significant metabolic alkalosis and an
      increase in urine pH. Both sodium bicarbonate and sodium chloride produced a
      profound diuresis. After sodium bicarbonate and sodium chloride treatments, the
      urinary concentration of etorphine, measured by radioimmunoassay (RIA), was
      reduced and in some cases could not be detected. Extraction of the urine samples,
      prior to RIA analysis, increased the sensitivity of the assay and in most cases
      gave a positive result. We conclude that the coadministration of etorphine and
      sodium bicarbonate or sodium chloride can make the detection of etorphine more
      difficult because of the dilutional effects associated with the administration of
      a large electrolyte load.

PMID- 8868398
TI  - alpha-benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit
      methamphetamine synthesis: III. Detection of BNMPA and metabolites in urine of
      methamphetamine users.
AB  - Eighty urine specimens collected from drug rehabilitation programs, which had
      been screened by immunoassay and confirmed positive by gas chromatography-mass
      spectrometry (GC-MS) for methamphetamine, were further analyzed for alpha-benzyl
      N-methylphenethylamine (BNMPA) and its urinary metabolites, N-demethyl-BNMPA,
      diphenyl-2-propanone (DP2P), diphenyl-2-propanol, p-OH-N-demethyl-BNMPA, and p-OH
      BNMPA. BNMPA is an impurity of illicit methamphetamine synthesis. Analysis of
      BNMPA and its metabolites was performed by quantitative GC-MS following beta
      glucuronidase hydrolysis, liquid-liquid extraction, and derivatization with
      heptafluorobutyric anhydride. Two urine specimens contained detectable amounts of
      BNMPA and/or its metabolites. One contained trace amounts (greater than the limit
      of detection but less than the limit of quantitation) of N-demethyl-BNMPA and
      DP2P, as well as 0.04 mg/L p-OH-N-demethyl-BNMPA. The other contained trace
      amounts of BNMPA, p-OH-BNMPA, and p-OH-N-demethyl-BNMPA, as well as 0.03 mg/L N
      demethyl-BNMPA. Prior to analyzing these urine specimens, pure reference material
      of p-OH-BNMPA was made available, and analysis confirmed our previous tentative
      identification of p-OH-BNMPA as a major metabolite of BNMPA. Detection of BNMPA
      or its metabolites in biological samples may serve as a marker of illicit
      methamphetamine administration.

PMID- 8868399
TI  - A screening procedure for the determination of 13 oral anticoagulants and
      rodenticides.
AB  - A technique for the simultaneous identification and quantitation of 13
      hydroxycoumarin and indandione anticoagulant drugs and rodenticides from human
      serum by reversed-phase liquid chromatography with diode-array detection has been
      developed. High-performance liquid chromatography was performed using gradient
      elution with an acetonitrile and phosphate buffer on a Nucleosil ODS column.
      Ultraviolet spectra from 200 to 400 nm were recorded on-line during the analysis
      and compared with spectra stored in a library. For the spiked 2 mL of serum,
      acidic and alkaline liquid-liquid double extraction with diethylether-ether
      acetate (50:50, v/v) was conducted, and recoveries greater than 60% for most
      compounds were found. The detection limit was approximately 25 or 50 ng/mL for
      all components except for difethialone and fluindione, for which it was
      approximately 100 ng/mL. The standard calibration curves were linear from the
      detection limit to 5000 ng/mL. The within-run precision coefficient of variation
      (CV) was less than 10%, and the between-run precision CV was less than 20%.

PMID- 8868401
TI  - Fluorometric HPLC determination of delta-aminolevulinic acid (ALA) in the plasma
      and urine of lead workers: biological indicators of lead exposure.
AB  - A fluorometric high-performance liquid chromatographic (HPLC) method was
      developed for the highly sensitive measurement of delta-aminolevulinic acid (ALA)
      in biological materials. By using this method, we determined ALA in the plasma
      and urine of 418 workers occupationally exposed to lead and in the plasma and
      urine of 227 controls. The concentrations of ALA in the plasma and urine of lead
      workers were significantly elevated as compared with those of the controls. The
      concentration of ALA in plasma and urine was highly correlated with that of lead
      in blood in lead workers. It was found that the correlation (r = 0.742) between
      log of plasma ALA concentrations and blood lead concentrations in lead workers
      was similar to that (r = 0.711) between log of urine ALA concentrations and blood
      lead concentrations. These results demonstrated that the measurement of ALA in
      plasma or in urine using a fluorometric HPLC method was useful for the biological
      monitoring of lead workers.

PMID- 8868400
TI  - Application of HPLC with silica-phase and reversed-phase eluents for the
      determination of clomipramine and demethylated and 8-hydroxylated metabolites.
AB  - A rapid and efficient high-performance liquid chromatographic method using a
      reversed-phase eluent of methanol-water with butylamine on a silica column was
      developed for the separation and quantitation of clomipramine (CMI), its
      demethylated metabolites (desmethyl-clomipramine and didesmethyl-clomipramine
      [DDCMI]), and its hydroxylated metabolites (8-hydroxy-clomipramine and 8-hydroxy
      desmethylclomipramine). A liquid-liquid extraction procedure, which involved an
      alkaline extraction with heptane-isoamyl alcohol, first from a 1-mL serum sample
      and then from the acidic back extract, was used. The chromatographic separation
      was rapid (20 min), and the ultraviolet detection (at 254 nm) was sufficiently
      sensitive (limit of detection, 5-10 ng/mL). Except for DDCMI, the calibration was
      linear (r > 0.99, n = 5), and within-day and day-to-day coefficients of variation
      remained less than 11%. The method was used to analyze CMI and its metabolites in
      the serum of depressive patients and to determine their hydroxylation and
      demethylation capacities.

PMID- 8868402
TI  - Hair testing for cannabis in Spain and France: is there a difference in
      consumption?
AB  - This paper compares the methods used in Sevilla, Spain with those used in
      Strasbourg, France for analyzing cannabinoids (delta 9-tetrahydrocannabinol [THC]
      and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid [THCCOOH]) in human
      hair. The Sevilla procedure involved the following steps: After washing the hair
      samples with methylene chloride at 37 degrees C for 15 min, hydrolysis was
      performed with 11.8N KOH (in the presence of THC-d3 and THCCOOH-d3) for 10 min at
      laboratory temperature, followed by the addition of maleic acid, extraction with
      n-hexane-ethyl acetate, and derivatization with heptafluorobutyric anhydride and
      hexafluoroisopropanol. Concentrations within the Spanish population ranged from
      0.06 to 7.63 ng/mg and from 0.05 to 3.87 ng/mg for THC and THCCOOH, respectively.
      The Strasbourg procedure involved the following steps: Samples were
      decontaminated twice with methylene chloride, then pulverized and dissolved in 1N
      NaOH in the presence of THC-d3 and THCCOOH-d3. After cooling, acetic acid was
      added, and the samples were extracted with n-hexane-ethyl acetate, followed by a
      cleanup step with NaOH and HCl. Derivatization with pentafluoropropionic
      anhydride-pentafluoro-propanol was followed by gas chromatographic-mass
      spectrometric analysis using negative chemical ionization. Concentrations within
      the French population ranged from 0.10 to 2.17 ng/mg and from 0.05 to 0.39 ng/mg
      for THC and THCCOOH, respectively. In order to validate both analytical methods,
      10 real hair samples from known drug abusers were analyzed by both procedures.
      The differences in the results ranged from 2 to 43% (mean, 25.7%) for THC and
      from 0 to 73.7% (mean, 36.8%) for THCCOOH. After comparing the cannabis results
      in hair in Spain (70 cases) and France (98 cases), we found quantitative as well
      as qualitative differences in cannabis consumption in the two populations.

PMID- 8868403
TI  - Identification of alpha-phenylethylamine in judicial samples.
AB  - alpha-Phenylethylamine was recently identified in samples from several judicial
      cases using chromatographic (high-performance liquid chromatography-diode-array
      detection, gas chromatography-mass spectrometry, and gas chromatography-Fourier
      transform infrared detection) and spectrometric (nuclear magnetic resonance)
      techniques. In the first case, 1 kg of a white powder was found in a basement
      laboratory. It contained caffeine and more than 15% alpha-phenylethylamine. In
      the second case, two white powders were seized from a female. One powder
      consisted of pure amphetamine, and the other was a mixture of caffeine,
      amphetamine, and alpha-phenylethylamine. Four months later, a couple, who were
      known drug users, were found dead in their apartment. Urine samples of both
      victims contained large amounts of amphetamine together with alpha
      phenylethylamine. Recently, 0.13 kg of a white powder and 0.30 kg of an orange
      powder were seized during a law enforcement operation. Both powders were mixtures
      of caffeine, amphetamine, and alpha-phenylethylamine. The data presented
      demonstrate the recent and unrelated repetitive occurrence of alpha
      phenylethylamine in the circuit of illicit drugs.

PMID- 8868404
TI  - The effect of hair color on the incorporation of methadone into hair in the rat.
AB  - Six groups of six male, hooded, Lister rats were administered methadone in their
      drinking water over the concentration range 0-0.25 mg/mL for 6 weeks. Black
      pigmented and white nonpigmented hair and trunk blood samples were collected.
      Plasma and alkali digests of hair were analyzed for methadone by
      radioimmunoassay. Hair melanin content was estimated in digests by turbidimetry.
      Oral methadone intake rose in a linear fashion over the six dose groups, and
      plasma methadone concentration followed a similar trend. The methadone content of
      both white and black hair increased over the six dose groups, but concentrations
      were significantly higher in black compared with white hair. The mean ratio of
      methadone concentration between black and white hair was 21.3:1, and the mean
      ratio in hair melanin content was 3.5:1. The results demonstrate that pigmented
      hair incorporates larger quantities of methadone than nonpigmented hair and that
      methadone binds with higher affinity to the pigmented components as compared with
      other components of hair.

PMID- 8868405
TI  - Hair analysis for drugs of abuse XII. Determination of PCP and its major
      metabolites, PCHP and PPC, in rat hair after administration of PCP.
AB  - We developed an analytical method for the simultaneous detection of phencyclidine
      (PCP) and its metabolites, 4-phenyl-4-piperidinocyclohexanol (PPC) and 1-(1
      phenylcyclohexyl)-4-hydroxypiperidine (PCHP), in rat hair. Three pigmented, hairy
      rats were intraperitoneally administered PCP hydrochloride (HCl) at 0.05-0.5
      mg/kg once a day for 10 successive days. Animal hair was shaved just before the
      first administration, and the newly grown hair was collected 4 weeks after the
      first administration. After the rat hair sample was washed three times with 0.1%
      sodium dodecyl sulfonate and water, separately, and dried in a desiccator, 20 mg
      of finely cut hair was extracted with 2 mL methanol-5N HCl (20:1) under
      ultrasonication for 1 h, followed by storage at room temperature for 14 h.
      Following filtration and evaporation of the extract, it was purified with Bond
      Elut Certify in the usual manner, and the extract was derivatized with N,O
      bis(trimethylsilyl) acetamide for gas chromatographic-mass spectrometric analysis
      using deuterated PCP, PPC, and PCHP as internal standards. The selected ions were
      monitored at m/z 186, 200, and 242 for PCP, m/z 172, 288, and 331 for
      trimethylsilyl (TMS) PCHP, and m/z 200, 254, and 331 for TMS PPC. PCP, PCHP, and
      PPC were simultaneously detected in the rat hair down to 0.1 mg/kg PCP HCl. Even
      at the dose of 0.05 mg/kg, PCP was clearly detected in the rat hair. Based on the
      area under the concentration versus time curve (AUC) in plasma (1460 ng.min/mL),
      the PCP concentration (3.34 ng/mg) in the rat hair was quite high. The
      incorporation rates into hair (concentration in hair/AUC) of PCP, PCHP, and trans
      PPC were 2.29, 1.65, and 0.50, respectively, at 0.5 mg/kg. Our results suggest
      that hair could be a useful specimen for confirmation of active past PCP use
      because PCP and its metabolites can be detected simultaneously.

PMID- 8868406
TI  - Two cases of fatal zopiclone overdose.
AB  - Two cases of death due to the ingestion of zopiclone are presented. Quantitative
      determinations of zopiclone yielded 1.4-3.9 mg/L in the blood, 0.81 and 8.7 mg/kg
      in the liver, and 13.5 and 133 mg in the stomach contents. Drug concentrations
      were interpreted relative to the case findings, published data, and a limited
      evaluation of therapeutic concentrations found in two cases of therapeutic
      zopiclone use. Zopiclone was extracted from buffered blood or digested liver or
      both with n-butyl chloride and analyzed by high-performance liquid chromatography
      with ultraviolet detection. Liver samples were digested at pH 7 to avoid
      zopiclone decomposition.

PMID- 8868407
TI  - Analytical findings in a suicide involving sodium azide.
AB  - A 47-year-old laboratory assistant ingested approximately 9 g of sodium azide
      powder and died 4 h later at a hospital. A high-performance liquid
      chromatographic method using diode-array detection has been developed for the
      determination of an azide benzoyl derivative in blood (after a simple
      deproteinization) and in several tissues (after homogenization in a neutral
      buffer and deproteinization of the supernatant). The blood concentration in this
      case was lower than those previously published. The highest azide concentration
      was found in lung tissue. A complete toxicological screening revealed the
      presence of cyanide in blood, which has been previously reported twice, but for
      the first time, it was confirmed by mass spectrometry. Whether the production of
      cyanide in the presence of azide took place in vivo or postmortem remains
      unknown; the nature of the metabolic pathway involved also remains unknown.

PMID- 8868408
TI  - Cocaine excretion in the semen of drug users.

PMID- 8868409
TI  - Disclosing recent drinking after alcohol has been cleared from the body.

PMID- 8868410
TI  - Let's not overlook nicotine.

PMID- 8868411
TI  - Head extension and age-dependent posturographic instability in normal subjects.
AB  - We have investigated the role of head extension in posturographic testing of
      normal subjects. We especially wished to determine the number of falls that
      occurred in the "normal" elderly so as to distinguish them from elderly patients
      with abnormal neurologic and vestibular patterns. We tested 144 normal subjects
      ages 22 to 85, the majority older than 60 years, with the NeuroCom Equitest
      sensory posturography protocol: first with their heads erect and then with their
      heads extended 55 degrees. None of our subjects younger than age 59 experienced a
      fall during sensory posturography tests with their heads erect. However, 35 of
      the 101 older subjects exhibited a total of 79 falls during these same tests.
      When the tests were repeated with the head extended 55 degrees, the number of
      falls for the whole group increased from 79 to 171. Where only 24% of all the
      subjects fell with head erect, 52% fell with head extended. The increase was
      especially notable among the elderly. Head extension increases the difficulty of
      performing certain posturography tests and has been useful in uncovering
      compensated deficits in equilibrium in young and middle-aged patients. However,
      because head extension significantly increases falls among normal elderly
      subjects, this does not seem to be an effective tool to determine abnormality in
      this age group.

PMID- 8868412
TI  - Effects of age and disability on tracking tasks with a computer mouse: accuracy
      and linearity.
AB  - Many individuals with movement disorders are unable to make efficient use of
      graphical computer interfaces commonly employed in personal computers. In this
      study, performance limitations in target tracking with a computer mouse were
      studied for eight young subjects aged 19 to 29 (M = 23, SD = 3), four old
      subjects aged 70 to 73 (M = 72, SD = 1), and five motor-disabled subjects aged 37
      to 74 (M = 65, SD = 16). Subjects tracked simple one- and two-dimensional motions
      at various frequencies. Performance was measured using an accuracy index derived
      from root-mean-square error, and a linearity index based on coherence estimation.
      A maximum bandwidth of 2 Hz for accuracy of mouse use was found, which often
      decreased due to advanced age or motor disability. Tracking linearity of all
      groups decreased as frequency increased. A significant degree of nonlinearity
      existed in all results (p < 0.05), with disabled subjects nearing complete
      nonlinearity in two-dimensional tracking. The data show that with advanced age
      and disability, mouse use becomes increasingly inaccurate and nonlinear.
      Assistive computer interfacing techniques, such as signal filtering, may improve
      mouse use.

PMID- 8868413
TI  - Use of bivalved ankle-foot orthosis in neuropathic foot and ankle lesions.
AB  - The neuropathic foot is a common complication of diabetes mellitus and is
      associated with development of chronic ulcers and Charcot joints. Treatment of
      these complications presents a complex management task. This report presents long
      term follow-up data on 16 patients with neuropathic changes who were treated with
      a total contact, laminated, bivalved, rocker-bottom-soled ankle-foot orthosis
      (TCAFO). Of the 16 patients, 6 were treated for Charcot changes only, 10 were
      treated for ulcers, and 2 of the 10 had ulcers bilaterally. Eight of the 12
      ulcers (67%) healed in an average of 10 months (range 1-24 mo), 1 patient
      required amputation, and 2 patients who had complete healing, 5 have resumed
      wearing TCAFOs secondary to recurrent ulcers. Three of the 5 patients with
      Charcot changes no longer use the orthosis and have had negative bone scans after
      an average of 20.7 months (range 12-28 mo). In this retrospective uncontrolled
      study, the TCAFO proved to be a safe, functional, and cost-effective therapy for
      complications of the neuropathic foot.

PMID- 8868414
TI  - Development of instrumentation and protocol to measure the dynamic environment of
      a modified van.
AB  - The dynamic environment of a van modified to accommodate a person driving from a
      wheelchair was measured to determine the effects of position within the van and
      the type of seat used. The project measured accelerations as a subject sat in
      three positions within the van and upon two different seats. Three separate van
      maneuvers at different speeds were used to change the dynamic environment. Van
      accelerations at the different positions varied significantly. A wheelchair
      transmitted more accelerations to the subject than the original equipment
      manufacturers (OEM) seat, making it harder to maintain a stable posture. These
      results should prove useful to others studying the functional abilities of
      wheelchair users within a vehicle environment.

PMID- 8868415
TI  - Stability of walking frames.
AB  - Biomechanical tools were used to assess stability for 11 patients who, following
      the surgical amputation of one lower limb, required the assistance of a walking
      frame to ambulate. The Walker Tipping Index (WTI), as derived from the forces
      applied to the walking frame, was developed specifically for this study to
      examine the relationship between stability and walking frame height during
      ambulation. However, the WTI may be useful as a criterion of stability to assist
      clinicians in their evaluation of walker use in a variety of patient populations.
      Walker stability was examined as subjects, wearing their prostheses, completed 30
      sec walking trials in each of the normal, high, and low walking frame height
      conditions. Adjusting the height of the walker to one setting (3 cm) above or
      below normal appears to redistribute the load of walking between the upper and
      lower extremities without adversely affecting stability.

PMID- 8868416
TI  - Test-retest reliability of the Chattecx Balance System in the patient with
      hemiplegia.
AB  - The purpose of this study was to determine the test-retest reliability of the
      Chattecx Balance System in the patient with hemiplegia. Twenty patients (14 male,
      6 female; 14 right hemiplegia, 6 left; mean age 69.5, range 32-86 years)
      undergoing physical therapy, were tested on the Chattecx Balance System at the
      same time on 3 consecutive days. Subjects were tested on a static platform, and
      also using linear translation (anterior-posterior movements), and rotational
      angular motion about a mediolateral axis. Day 1 was used to allow the patient to
      become familiar with the testing equipment and the protocol. Data collected from
      days 2 and 3 were compared statistically using Intraclass Correlation Coefficient
      (ICC) formula 3,1. Comparison of the center of pressure in the mediolateral
      direction (COBX), the center of pressure in the anteroposterior direction (COBY),
      and dispersion index were analyzed for each of the three protocols. ICCs ranged
      from 0.58 to 0.92 for the static platform, 0.46 to 0.83 for the linear
      translations, and 0.62 to 0.89 for the angular rotations. Results using this
      testing protocol showed COBX to be highly reliable for the static and moderately
      reliable for linear and angular testing protocols. COBY was not reliable for any
      test condition. Dispersion was moderately reliable only for the static and
      angular testing protocols. From a clinical standpoint, measures that were found
      to be highly or moderately reliable may be useful for demonstrating the progress
      of patients with hemiplegia in their rehabilitation programs.

PMID- 8868418
TI  - Clinical evaluation of the Modular Electromechanical Lock Actuator (MELA) for
      above-elbow prostheses: a final report.
AB  - The Modular Electromechanical Lock Actuator (MELA) is the result of research and
      development (R&D) conducted under the direction of Dudley S. Childress, PhD, at
      the Northwestern University Prosthetics Research Laboratory (NUPRL), Chicago,
      Illinois. NUPRL, based upon experience with prostheses for persons with high
      level, above-elbow amputations, developed the MELA to assist those persons with
      amputation who experience difficulty in operating existing manual elbows, whether
      with a conventional harness, nudge control, excursion amplifier, or other
      arrangement. Technology Transfer Section, VA Rehab R&D, with collaboration from
      Frederick Downs, Jr., Director, and John Clements, Prosthetic Regional Manager,
      VA National Prosthetic and Sensory Aids Service, managed a multicenter clinical
      evaluation of the MELA. The purpose was to objectively assess and affirm its
      performance, safety, clinical application, and commercial readiness. The
      following VA Prosthetic Treatment Centers served as evaluation sites: Baltimore,
      MD, Huntington, WV, and New York, NY. A VA-wide screening process yielded 10
      candidates for review. A total of seven subjects met the selection criteria and
      were accepted for participation. In addition, several prosthetists provided their
      comments on the MELA. Overall, the performance of the MELA demonstrated that it
      could be fit to existing body-powered arms and used as an alternative control
      method for manual elbows. Consensus of participant feedback indicated general
      satisfaction and improved elbow lock function. In addition, several modifications
      were identified for the commercial version. The primary issues focused on 1)
      increasing speed (alternating response time); 2) unloading forearm (sometimes
      required to cycle the MELA); 3) providing mechanical back-up in case of unit
      failure; 4) reducing gear-motor noise; 5) improving integrity of wiring and
      retaining clip; and 6) marketing the MELA as a stand-alone product. Hosmer
      Dorrance Corp., in collaboration with the developer, has indicated that
      resolution for most of the identified issues is readily achievable. Increasing
      speed (response time) and unloading forearm will require more investigation and
      consumer feedback from the commercial market. Based upon the clinical findings,
      the MELA was recommended for commercial production and availability, upon
      prescription, to appropriate veteran beneficiaries.

PMID- 8868417
TI  - Life-cycle analysis of depot versus rehabilitation manual wheelchairs.
AB  - The proper selection of a wheelchair requires making several critical decisions,
      not the least of which is what type of wheelchair is appropriate. The
      International Organization for Standards (ISO) continues to develop and refine
      wheelchair standards. Standards allow the objective comparison of products from
      various sources, permitting consumers or clinicians to assess wheelchairs with
      which they are not familiar by comparing test results. This study consisted of
      three components: 1) the comparison of fatigue test results with a planar
      ANSI/RESNA test dummy to a HERL contoured test dummy; 2) the comparison of
      fatigue test results for common depot versus common rehabilitation manual
      wheelchairs; and 3) the comparison of fatigue test results for manual
      rehabilitation wheelchairs with solid 8-inch casters versus those with pneumatic
      8-inch casters. Rehabilitation wheelchairs lasted on average 13.2 times longer
      than the depot wheelchairs. Both types, tested with the standard ISO-ANSI/RESNA
      dummy, lasted on average 2.1 times longer than those wheelchairs tested using the
      contoured dummy. The three rehabilitation wheelchairs equipped with 8-inch
      pneumatic casters lasted on average 3.2 times longer than the 6 rehabilitation
      wheelchairs equipped with solid 8-inch casters. The depot wheelchairs cost about
      3.4 times as much to operate per cycle or per meter than the rehabilitation
      wheelchairs. The rehabilitation wheelchairs tended to experience component
      failures, while the depot wheelchairs tended to experience frame failures. Our
      testing indicates that the tests in the ISO-ANSI/RESNA standards can relate
      design features to fatigue test results and durability. Rehabilitation
      wheelchairs tend to use higher quality materials and better manufacturing
      practices, and they provide greater mobility for wheelchair users. Purchasers and
      prescribers of wheelchairs should consider the life-cycle cost and not just the
      purchase price for wheelchairs.

PMID- 8868419
TI  - Cytosine accumulation as a measure of the proton electrochemical gradient acting
      on the overexpressed cytosine permease of Saccharomyces cerevisiae.
AB  - The magnitude of the proton gradient (delta mu H+) driving solute accumulation in
      Saccharomyces cerevisiae has long been in doubt, principally because of the lack
      of an agreed method for assaying its electrical component, the membrane potential
      (delta psi). In the present work, the size of the cytosine gradient (delta mu
      cyt) that the yeast generated was used as a measure of the driving gradient
      (delta mu H+). The selected yeast lacked cytosine deaminase and overexpressed
      cytosine permease, a 1 H+/cytosine system. delta mu cyt, assayed in washed cell
      suspensions fermenting glucose and containing 0.5 or 50 mM KCl, was about 260 mV
      at pH 4 or 5, falling to about 194 mV at pH 7. As a first estimate, -delta mu H+
      was thus at least as large at the respective pH value. A 20 mM solution of the
      lipophilic cation tetraphenylphosphonium lowered delta mu cyt to a value roughly
      equal to the magnitude of the pH gradient (delta pH). A mathematical model was
      used to correct the first estimates of delta mu H+ for the effect of cytosine
      leakage outside the symport. In such a system, delta mu cyt cannot exceed the
      equivalent ratio Vmax/KmL, where Vmax and Km are kinetic parameters of the
      symport and L is the rate coefficient for leakage. The feasibility of assaying
      delta mu H+ depends on it not being much larger than that ratio. The model was
      tested successfully against observations made with yeast preparations depleted of
      ATP. After correction, -delta mu H+ during fermentation was estimated to be up to
      25 mV larger than delta mu cyt and at least 70 mV larger than previous estimates
      in the literature involving lipophilic cations. From a knowledge of delta pH,
      delta psi was in turn deduced and compared with the maximum methylamine gradient
      (delta mu M) the yeast formed. The results supported the claim in the literature
      that, at acid pH, delta mu M is a measure of delta psi.

PMID- 8868420
TI  - High cAMP levels antagonize the reprogramming of gene expression that occurs at
      the diauxic shift in Saccharomyces cerevisiae.
AB  - In order to analyse the involvement of the cAMP pathway in the regulation of gene
      expression in Saccharomyces cerevisiae, we have examined the effect of cAMP on
      protein synthesis by using two-dimensional gel electrophoresis. cAMP had only a
      minor effect on the protein pattern of cells growing exponentially on glucose.
      However, it interfered with the changes in gene expression normally occurring
      upon glucose exhaustion in yeast cultures, maintaining a protein pattern typical
      of cells growing on glucose. This effect was accompanied by a delay before growth
      recovery on ethanol. We propose a model in which the cAMP-signalling pathway has
      a role in the maintenance of gene expression, rather than in the determination of
      a specific programme. A decrease of cAMP would then be required for metabolic
      transitions such as the diauxic phase.

PMID- 8868421
TI  - Alteration in membrane fluidity and lipid composition, and modulation of H(+)
      ATPase activity in Saccharomyces cerevisiae caused by decanoic acid.
AB  - Decanoic acid, a lipophilic agent, inhibited in vitro the plasma membrane H(+)
      ATPase of Saccharomyces cerevisiae grown in YPD medium. Conversely, when decanoic
      acid (35 microM) was present in the growth medium, the measured H(+)-ATPase
      activity was four times higher than that of control cells. Km, and pH and
      orthovanadate sensitivity were the same for the two growth conditions, which
      indicated that H(+)-ATPase activation was not due to conformational changes in
      the enzyme. The activation process was not entirely reversible which showed that
      plasma membrane H(+)-ATPase activation is due to several mechanisms. 1,6-diphenyl
      1,3,5-hexatriene anisotropy performed on protoplasts from cells grown in YPD
      revealed that as decanoic acid concentration was increased, anisotropy
      significantly decreased, i.e. membrance fluidity increased. Cells grown in media
      containing decanoic acid exhibited greater membrane fluidity compared with
      control cells. Furthermore, these cells did not show any fluidifying effect when
      increased concentrations of decanoic acid were added. Chemical analysis of cell
      membrane lipid composition revealed a modification in the distribution of the
      phospholipid fatty acids and sterols in cells grown in the presence of 35 microM
      decanoic acid compared with control cells. Our results support the view that the
      plasma membrane H(+)-ATPase activation induced by decanoic acid is correlated
      with an alteration in membrane lipid constituents.

PMID- 8868422
TI  - SYR2, a gene necessary for syringomycin growth inhibition of Saccharomyces
      cerevisiae.
AB  - The Pseudomonas syringae cyclic lipodepsipeptide syringomycin inhibits the growth
      of Saccharomyces cerevisiae. A novel yeast gene, SYR2, was found to complement
      two syringomycin-resistant S. cerevisiae mutants. SYR2 was cloned, sequenced, and
      shown to encode a 349 amino acid protein located in the endoplasmic reticulum.
      SYR2 was identical to SUR2, which is involved in survival during nutritional
      starvation. Gene disruption or overexpression of SYR2 did not affect cell
      viability or ergosterol levels, but did influence cellular phospholipid levels.
      The findings suggest that phospholipids are important for the growth inhibitory
      action of syringomycin.

PMID- 8868423
TI  - Candida albicans has a cell-associated ferric-reductase activity which is
      regulated in response to levels of iron and copper.
AB  - For survival, pathogenic organisms such as Candida albicans must possess an
      efficient mechanism for acquiring iron in the iron-restricted environment of the
      human body. C. albicans can use iron from a variety of sources found within the
      host. However, it is not clear how biologically active ferrous iron is obtained
      from these sources. One strategy adopted by some organisms is to reduce iron
      extracellularly and then specifically transport the ferrous iron into the cell.
      We have shown that clinical isolates of C. albicans do have a cell-associated
      ferric-reductase activity. The determination of ferric-reductase activity of
      cells growing exponentially in either low- or high-iron media over a period of
      time indicated that C. albicans reductase activity is induced when in low-iron
      conditions. Moreover, we have demonstrated that C. albicans reductase activity is
      also regulated in response to the growth phase of the culture, with induction
      occurring upon exit from stationary phase and maximal levels being reached in
      early exponential stage irrespective of the iron content of the medium. These
      results suggest that C. albicans reductase activity is regulated in a very
      similar manner to the Saccharomyces cerevisiae ferric-reductase. Iron reduction
      and uptake in S. cerevisiae are closely connected to copper reduction, and
      possibly copper uptake. In this report we show that iron and copper reduction
      also appear to be linked in C. albicans. The ferric-reductase activity is
      negatively regulated by copper. Moreover, quantitative cupric-reductase assays
      indicated that C. albicans is capable of reducing copper and that this cupric
      reductase activity is negatively regulated by both iron and copper. This is the
      first report that C. albicans has an iron- and copper-mediated ferri-reductase
      activity.

PMID- 8868424
TI  - Acid proteinase secreted by Candida tropicalis: functional analysis of
      preproregion cleavages in C. tropicalis and Saccharomyces cerevisiae.
AB  - The 40 kDa secreted aspartyl proteinase (Sapt1) of Candida tropicalis is a pepsin
      like enzyme encoded by the SAPT1 gene. According to the deduced amino acid
      sequence. Sapt1 has a putative preproregion of 60 amino acids preceding the
      mature enzyme. Maturation and processing of Sapt1 was analysed in C. tropicalis
      and Saccharomyces cerevisiae strains expressing wild-type or mutated forms of
      SAPT1. In S. cerevisiae, the glycosylated 46 kDa proenzyme was converted to the
      mature 40 kDa form of Sapt1 by KEX2-dependent proteolytic cleavage following the
      Lys59-Arg60 sequence. The replacement of Lys59-Arg60 by Lys59-Gly60 revealed that
      the precursor can be processed by an autocatalytic cleavage. This alternative
      processing pathway to produce mature Sapt1 is less efficient than the Kex2
      mediated pathway. Finally, it was shown that in C. tropicalis and S. cerevisiae
      the removal of the proregion was a prerequisite for the secretion of Sapt1.

PMID- 8868425
TI  - nuvA, an Aspergillus nidulans gene involved in DNA repair and recombination, is a
      homologue of Saccharomyces cerevisiae RAD18 and Neurospora crassa uvs-2.
AB  - A 40 kb genomic clone and 2.3 kb EcoRI subclone that rescued the DNA repair and
      recombination defects of the Aspergillus nidulans nuvA11 mutant were isolated and
      the subclone sequenced. The subclone hybridized to a cosmid in a chromosome
      specific library confirming the assignment of nuvA to linkage group IV and
      indicating its closeness to bimD. Amplification by PCR clarified the relative
      positions of nuvA and bimD. A region identified within the subclone, encoding a
      C3HC4 zinc finger motif, was used as a probe to retrieve a cDNA clone. Sequencing
      of this clone showed that the nuvA gene has an ORF of 1329 bp with two introns of
      51 bp and 60 bp. Expression of nuvA appears to be extremely low. The putative
      NUVA polypeptide has two zinc finger motifs, a molecular mass of 48906 Da and has
      39% identity with the Neurospora crassa uvs-2 and 25% identity with the
      Saccharomyces cerevisiae RAD18 translation products. Although mutations in nuvA,
      uvs-2 and RAD18 produce similar phenotypes, only the nuvA11 mutation affects
      meiotic recombination. A role for nuvA in both DNA repair and genetic
      recombination is proposed.

PMID- 8868426
TI  - Polyamines as modulators of microcycle conidiation in Aspergillus flavus.
AB  - Since polyamines (PAs) play a potential role in the regulation of growth and
      developmental processes in a wide variety of organisms, we have examined the
      influence of the PAs putrescine (Put) and spermidine (Spd) and the PA
      biosynthetic inhibitors alpha-difluoromethylornithine (DFMO), alpha
      difluoromethylarginine (DFMA), methylglyoxal bis-(guanylhydrazone) (MGBG) and
      cyclohexylamine (CHA), singly and in combinations on microcycle conidiation (MC)
      in Aspergillus flavus. The exogenous application of the diamine Put
      (concentrations ranging from 0.1 to 5 mM) caused a sharp decline of MC in a dose
      dependent fashion, but induced vegetative growth. However, the triamine Spd (0.1
      5 mM) had a minimal effect on MC and induced a shift from MC to normal condition.
      PA inhibitors, especially DFMO, MGBG and CHA, produced greater inhibition of MC
      and complete inhibition of MC was observed at 5 mM of these inhibitors. DFMA even
      at 5 mM had only a weak inhibitory effect on MC. DFMO also inhibited conidial
      germination and germ tube growth. MGBG and CHA, while having an inhibitory effect
      on MC, induced vegetative growth. The inhibitory effect of PA inhibitors was
      partially reversed by exogenous Put or Spd, with Spd being more effective than
      Put. The analysis of free PA levels during various phases of MC revealed that
      undifferentiated spores contained a high Put/Spd ratio and there was a dramatic
      decrease in Put/Spd ratio before and during microcycle conidiophore maturity. The
      change in spermine titres could not be detected. These observations imply that
      Put is essential for vegetative growth, while Spd is involved in MC, and that a
      low Put/Spd ratio seems to be important for spore differentiation to MC.

PMID- 8868427
TI  - How do highly branched (colonial) mutants of Fusarium graminearum A3/5 arise
      during Quorn myco-protein fermentations?
AB  - Chlorate-resistant, highly branched (colonial) mutants and auxotrophic mutants
      were used to study the nuclear distribution, morphology and growth of
      heterokaryons of the Quorn myco-protein fungus, Fusarium graminearum A3/5. The
      results showed that for several complementary homokaryons, even a strong
      selective pressure was insufficient to maintain heterokaryons in a 'balanced'
      condition (i.e. exhibiting a wild-type or near wild-type phenotype). Furthermore,
      the margins of heterokaryotic colonies generally contained nuclei from only one
      of the parental homokaryons, indicating imperfect nuclear mixing within the
      mycelium. These observations suggest that recessive, colonial mutants may appear
      during Quorn myco-protein production following shear-induced separation of hyphal
      fragments which contain a sufficiently high ratio of colonial:wild-type nuclei
      for the colonial phenotype to be expressed.

PMID- 8868428
TI  - The Gibberella fujikuroi niaD gene encoding nitrate reductase: isolation,
      sequence, homologous transformation and electrophoretic karyotype location.
AB  - The Gibberella fujikuroi niaD gene, encoding nitrate reductase, has been isolated
      and used to develop an efficient homologous transformation system. A cosmid
      vector designated pGFniaD was generated based on niaD selection and shown to give
      comparable transformation efficiencies. Using pGFniaD, a genomic library was
      prepared and used for genetic transformations, giving frequencies of up to 200
      transformants per microgram DNA. Of 15 transformants analysed by Southern blots,
      six showed homologous integration whilst the remaining nine integrated at
      heterologous sites, indicating that the vector may be used reliably for both
      types of integration. The system therefore may be used both for self-cloning of
      gibberellin biosynthetic genes on the basis of complementation of defective
      mutants, and also for gene disruption experiments. Electrophoretic karyotype
      determination suggested at least 11 chromosomes ranging from 2 to 6 Mb, the total
      genome size being at least 37 Mb. The niaD gene was assigned to chromosome V by
      Southern blot analysis. The niaD gene is interrupted by one intron, and
      remarkably the promoter sequence, but not the 3' untranslated sequence, is highly
      homologous to that of the corresponding Fusarium oxysporum gene. This situation
      appears to be unique with respect to the promoter regions of corresponding genes
      in related species of filamentous fungi.

PMID- 8868429
TI  - Reclassification of the Penicillium roqueforti group into three species on the
      basis of molecular genetic and biochemical profiles.
AB  - Penicillium roqueforti is currently divided into two varieties, one used for
      cheese starter cultures, P. roqueforti var. roqueforti, and one ubiquitous
      patulin-producing variety, P. roqueforti var. carneum. The ribosomal regions
      comprising the 5.8S gene and the internal transcribed spacers, ITS I and ITS II,
      have been analysed from 10 isolates belonging to each variety. The 10 P.
      roqueforti var. carneum isolates were separated into two groups of five on the
      basis of 12 base-pair differences in the ITS regions. One of the groups of P.
      roqueforti var. carneum, in the following designated P. carneum, differed from P.
      roqueforti var. roqueforti, here designated P. roqueforti, in just two positions,
      while the other group, here called P. paneum, differed from P. roqueforti in 12
      positions. Random Amplified Polymorphic DNA (RAPD) analysis substantiated these
      findings, and a comparison of secondary metabolites produced by the three groups
      showed that the P. roqueforti isolates all produce Penicillium Roqueforti (PR)
      toxin, marcfortines and fumigaclavine A, while the P. carneum isolates produce
      patulin, penitrem A and mycophenolic acid, as well as unidentified metabolites.
      P. paneum produces secondary metabolites in five chromophore families including
      the known mycotoxins patulin and botryodiploidin. On the basis of these findings
      it is proposed that P. roqueforti is reclassified into three species named P.
      roqueforti, P. carneum and P. paneum.

PMID- 8868430
TI  - Intra-specific diversity within Pasteurella trehalosi based on variation of
      capsular polysaccharide, lipopolysaccharide and outer-membrane proteins.
AB  - Intra-specific diversity within Pasteurella trehalosi was investigated by
      analysis of variation of capsular polysaccharide, and lipopolysaccharide (LPS)
      and outer-membrane protein (OMP) profiles. Sixty isolates of P. trehalosi, from
      diverse geographical locations within the UK, were examined. Capsular
      polysaccharide serotypes were determined by indirect haemagglutination assay; LPS
      and OMP profiles were compared by SDS-PAGE analysis. Capsular serotyping
      identified three isolates of serotype T3, 18 isolates each of serotypes T4, T10
      and T15, and three untypable (UT) isolates. Analysis of LPS and OMP profiles
      identified six smooth LPS types and four OMP types among the 60 isolates. Forty
      five (75%) of the isolates belonged to a single OMP type whereas 52 (87%) of the
      isolates possessed one of three LPS types. Each typing method, by itself, was not
      very discriminating but when the data from the three methods were combined, the
      60 isolates could be separated into 14 distinct subgroups containing from one to
      16 isolates as follows: serotype T3, two subgroups; serotype T4, four subgroups;
      serotype T10, two subgroups; serotype T15, five subgroups; UT isolates, one
      subgroup. Certain subgroups were associated with only one serotype whereas other
      subgroups were common to two or more serotypes. The subgroupings were capable of
      differentiating between isolates of the same serotype from the same and different
      geographical origins. Based on their LPS and OMP profiles, isolates of serotypes
      T4 and T15 were more closely related to each other than to isolates of serotype
      T10; serotype T4 and T15 isolates were also more heterogeneous than those of
      serotype T10. Certain isolates of serotype T10, recovered from a wide
      geographical area, were characterized by the possession of a unique
      capsule/LPS/OMP combination and represented a single clonal group which was
      responsible for a large proportion (31%) of recent disease outbreaks. Overall, a
      combination of capsular serotyping, and LPS and OMP typing, was found to be
      extremely useful for assessing diversity within P. trehalosi and should be of
      value for epidemiological and virulence studies.

PMID- 8868431
TI  - The application of serological techniques to the taxonomy of Arthrobacter and
      related organisms.
AB  - Antisera were raised against rods of 17 named Arthrobacter and Aureobacterium
      strains. Antigenic relationships between these strains, other soil bacteria and
      new Arthrobacter isolates from several soils were studied, using agglutination,
      immunodiffusion, immunofluorescence and ELISA techniques. Many of the named
      Arthrobacter species had common antigens, and there were also common antigens
      amongst named Arthrobacter strains and many fresh Arthrobacter isolates.
      Agglutination, ELISA and immunofluorescence tests revealed greater antigenic
      differences between the named strains than did immunodiffusion tests. Serological
      similarities between the 17 named strains and the fresh Arthrobacter isolates
      were calculated using SJ coefficients. The occurrence of named strains in
      serogroups based on immunodiffusion data supported the taxonomic scheme for
      arthrobacters in Bergey's Manual of Systematic Bacteriology. The distribution of
      soil isolates in serogroups resembled that in groups based on numerical analysis
      of diverse characters. This makes it possible to use serological tests to locate
      particular species in soil samples. Arthrobacter atrocyaneus was serologically
      distinct from other members of the Ar. globiformis/Ar. citreus group and did not
      cluster with them phenetically. Serological data suggest that Ar. aurescens, Ar.
      ureafaciens and Ar. histidinolovorans constitute a single species. Although A.
      simplex and A. tumescens have been placed in the genus Pimelobacter, they are
      serologically distinct from one another and more closely resemble Ar.
      globiformis. Aureobacterium strains were serologically distinct from
      arthrobacters. Micrococcus roseus showed many cross-reactions with several
      antisera, supporting the placement of micrococci in the same family as
      arthrobacters.

PMID- 8868432
TI  - Regulation of Escherichia coli adenylate cyclase activity during hexose phosphate
      transport.
AB  - In Escherichia coli, cAMP levels vary with the carbon source used in the culture
      medium. These levels are dependent on the cellular concentration of
      phosphorylated EnzymeIIAglc, a component of the glucose-phosphotransferase
      system, which activates adenylate cyclase (AC). When cells are grown on glucose 6
      phosphate (Glc6P), the cAMP level is particularly low. In this study, we
      investigated the mechanism leading to the low cAMP level when Glc6P is used as
      the carbon source, i.e. the mechanism preventing the activation of AC by
      phosphorylated EnzymeIIAglc. Glc6P is transported via the Uhp system which is
      inducible by extracellular Glc6P. The Uhp system comprises a permease UhpT and
      three proteins UhpA, UhpB and UhpC which are necessary for uhpT gene
      transcription. Controlled expression of UhpT in the absence of the regulatory
      proteins (UhpA, UhpB and UhpC) allowed us to demonstrate that (i) the Uhp
      regulatory proteins do not prevent the activation of AC by direct interaction
      with EnzymeIIAglc and (ii) an increase in the amount of UhpT synthesized
      (corresponding to an increase in the amount of Glc6P transported) correlates with
      a decrease in the cAMP level. We present data indicating that Glc6P per se or its
      degradation is unlikely to be responsible for the low cAMP level. It is concluded
      that the level of cAMP in the cell is determined by the flux of Glc6P through
      UhpT.

PMID- 8868433
TI  - Inducer expulsion and the occurrence of an HPr(Ser-P)-activated sugar-phosphate
      phosphatase in Enterococcus faecalis and Streptococcus pyogenes.
AB  - Inducer expulsion, a phenomenon in which rapidly metabolizable sugars cause
      cytoplasmic dephosphorylation and efflux of pre-accumulated sugar-phosphates
      (sugar-P), has been documented for Streptococcus pyogenes, Streptococcus bovis,
      and Lactococcus lactis, but not for other Gram-positive bacteria. Using intact
      cells and membrane vesicles, we show that Enterococcus faecalis exhibits both
      inducer exclusion and inducer expulsion, and that the latter phenomenon is
      dependent on the metabolite-activated ATP-dependent HPr(Ser) kinase that
      phosphorylates Ser-46 in HPr of the phosphotransferase system. A small, heat
      stable, membrane-associated, HPr(Ser-P)-activated sugar-P phosphatase (Pase II),
      previously identified only in Lc. lactis, is shown to be present in extracts of
      Enterococcus faecalis and Streptococcus pyogenes but not in those of
      Staphylococcus aureus, Streptococcus mutans, Streptococcus salivarius, or
      Bacillis subtilis, organisms that do not exhibit the inducer expulsion
      phenomenon. Further, Lactobacillus brevis, an organism that exhibits inducer
      expulsion by a different mechanism, also apparently lacks Pase II. The results
      reveal that Pase II is present in those organisms that exhibit the coupled sugar
      P hydrolysis/expulsion mechanism but not those that lack this mechanism. They
      provide correlative evidence that Pase II initiates inducer expulsion in species
      of enterococci, streptococci and lactococci.

PMID- 8868434
TI  - The behavioural response of anaerobic Rhodobacter sphaeroides to temporal
      stimuli.
AB  - The behavioural response of Rhodobacter sphaeroides to temporal changes in the
      concentration of chemoeffectors, and to stimuli affecting electron transport, was
      analysed using tethered cells. Populations of photosynthetically grown tethered
      cells of R. sphaeroides showed a transient response, a stop followed by
      adaptation, to a stepwise reduction in the concentration of chemoattractants
      (such as organic acids or sugars) and terminal electron acceptors. A step-down
      response was also measured in free swimming cells to a reduction in light
      intensity. As this response appears to apply to all effectors this suggests that
      there is a sensory pathway in anaerobically grown R. sphaeroides which responds
      primarily to a reduction in a stimulus. R. sphaeroides therefore responds when
      moving down a concentration gradient. This is the inverse of the classical
      Escherichia coli-Salmonella typhimurium model of bacterial sensory behaviour in
      which bacteria respond primarily when there is an increase in an attractant
      concentration, i.e. when moving up a gradient. R. sphaeroides does show a
      chemokinetic response to an increase in concentration of a limited number of
      compounds but this response is sustained and accompanied by an increase in the
      rate of flagellar rotation and therefore not simply equivalent to the transient
      increase in smooth swimming measured in E. coli on addition of an attractant.

PMID- 8868435
TI  - An essential role for actA in acid tolerance of Rhizobium meliloti.
AB  - The actA gene, which is disrupted by Tn5 in the acid-sensitive mutant of
      Rhizobium meliloti TG2-6, was cloned and sequenced. It encodes a protein of 541
      amino acids with a calculated molecular mass of 57,963 Da and an estimated pl of
      9.0. The ActA protein sequence has 30% identity, and much higher similarity
      (69%), with the CutE protein of Escherichia coli. Like the cutE mutant of E.
      coli, TG2-6 is sensitive to copper. The reconstructed wild-type actA gene
      complemented the low pH- and copper-sensitive phenotype of TG2-6. Studies with an
      actA-lacZ gene fusion showed that actA is constitutively expressed at pH 5.8 and
      7.0. The actA gene appears to be chromosomal and is present in all seven strains
      of R. meliloti tested.

PMID- 8868436
TI  - Effect of the nitrogen source on phycobiliprotein synthesis and cell reserves in
      a chromatically adapting filamentous cyanobacterium.
AB  - Cyanobacteria can utilize nitrate or ammonium as a source of fixed nitrogen for
      cell growth. In the filamentous Calothrix sp. strain PCC 7601, these two sources
      of nitrogen differently influenced the phycobiliprotein composition of the
      phycobilisomes, the major light-harvesting antennae. When compared to nitrate,
      growth in the presence of ammonium resulted in intracellular steady-state levels
      35% lower for phycoerythrin and 46% higher for phycocyanin. Besides these
      differences in cell pigmentation, a rapid but transient accumulation of
      cyanophycin granule polypeptide occurred in ammonium-grown cells, while these
      macromolecules were not detected in cells grown with nitrate. In contrast,
      glycogen reserves displayed a dynamic pattern of accumulation and disappearance
      during cell growth which varied only slightly with the nitrogen source. The
      observed changes in cell pigmentation are reminiscent of the phenomenon of
      complementary chromatic adaptation, in which green and red wavelengths promote
      the syntheses of phycoerythrin and phycocyanin-2, respectively. As in
      complementary chromatic adaptation, the regulation of synthesis of phycoerythrin
      and phycocyanin-2 by the nitrogen source occurred mainly at the mRNA level.
      Moreover, the transcriptional start sites for the expression of the cpeBA and the
      cpc2 operons, which respectively encode the two subunits of phycoerythrin and
      phycocyanin-2, were the same in cells grown in nitrate or ammonium, and identical
      to those in green- and red-light-grown cells. The results of this study suggest
      that acclimation to the spectral light quality and to the nitrogen source share
      some common regulatory elements.

PMID- 8868437
TI  - Effect of oxygen, inoculum composition and flow rate on development of mixed
      culture oral biofilms.
AB  - The effect of aeration on the development of a defined biofilm consortium of oral
      bacteria was investigated in a two-stage chemostat system. An inoculum comprising
      10 species, including both facultatively anaerobic and obligately anaerobic
      bacteria, and species associated with oral health and disease, was inoculated
      into an anaerobic first-stage chemostat vessel. The effluent from this chemostat
      was linked to an aerated [200 ml CO2/air (5:95, v/v) min-1] second-stage vessel,
      in which removable hydroxyapatite discs were inserted to allow biofilm formation.
      Comparisons were made of planktonic and biofilm communities in the aerated second
      stage vessel by means of viable counts. Both planktonic and early biofilm
      communities were dominated by Neisseria subflava, comprising > 40% of total
      c.f.u. in the fluid phase, and > 80% of c.f.u. in 2 h biofilms. Obligate
      anaerobes persisted in this mixed culture, and succession in biofilms led them to
      predominate only after 7 d. Despite the continuous addition of air, the dissolved
      oxygen tension (dO2) within the culture remained low (< 5% of air saturation),
      and the redox potential (Eh) was -275 mV. In order to assess the significance of
      the presence of N. subflava in community development, a subsequent experiment
      omitted this aerobe from the inoculum, to produce a nine-species culture. The
      planktonic phase was predominated by three streptococcal species, Prevotella
      nigrescens and Fusobacterium nucleatum. Biofilms again underwent successional
      changes, with anaerobes increasing in proportion with time. In contrast to the
      culture including N. subflava, dO2 was 50-60% of air saturation, and the Eh was
      +50 mV. In the final experiment, the rate of addition of first-stage culture was
      reduced to 1/10 of that in the previous experiment, in order to determine whether
      anaerobes were growing, rather than merely persisting in the aerated culture. The
      data for the planktonic phase indicated that the anaerobes were growing in
      aerated (dO2 40-50%, Eh +100 mV) conditions. Once again, anaerobes increased in
      proportion in older biofilms. The study indicates that mixed cultures can protect
      obligate anaerobes from the toxic effects of oxygen, both in the biofilm and
      planktonic modes of growth.

PMID- 8868438
TI  - Development of a steady-state oral microbial biofilm community using the constant
      depth film fermenter.
AB  - The complexity of biofilm communities like dental plaque suggests that laboratory
      model biofilm growth systems may help to understand their structure and function.
      This study describes the use of a constant-depth film fermenter (CDFF) to
      investigate biofilm formation by a nine-membered community of oral bacteria. The
      community was grown to steady state in a chemostat incubated anaerobically. The
      chemostat output was fed into the CDFF incubated aerobically. Viable counts for
      each species from the chemostat and the CDFF at steady state showed major
      differences; however, all nine organisms were present under both conditions.
      There was evidence of succession during biofilm formation with obligately
      anaerobic species only establishing after several days. A steady-state biofilm
      community was achieved which remained stable over time. Electron microscopy
      showed evidence of spatial differentiation with what appeared to be Neisseria
      subflava dominant near the upper surface and Fusobacterium nucleatum largely
      confined to the middle portion.

PMID- 8868439
TI  - Experimental verification of a mathematical model for pelleted growth of
      Streptomyces coelicolor A3(2) in submerged batch culture.
AB  - A published mathematical model for growth of pellets of filamentous
      microorganisms has been tested by comparison of model predictions with
      experimental data on growth of Streptomyces coelicolor in liquid batch culture.
      The original model considered the classification of pellets into a range of size
      classes. Growth resulted in movement of pellets to classes of increasing size,
      while shear forces produced mycelial fragments which entered the smallest size
      class, from which they grew to form further pellets. This model did not correctly
      describe changes in pellet size distributions during growth and was therefore
      modified in two ways. In the first, new pellets were assumed to be formed by the
      break-up, by shear forces, of existing pellets into two pellets of equal size,
      rather than removal of small hyphal fragments from the pellet surface. The second
      modification assumed that the outer shell of active mycelial biomass had a
      density less than 1 g cm-3 and that hyphal density within this shell decreased
      with distance from the pellet centre. The modified model generated predictions
      which agreed closely with experimental data on biomass concentration, pellet size
      distribution, pellet number and pellet radius during batch growth, thereby
      supporting the assumptions on which the model was based. The model did not
      accurately describe final biomass concentration, through lack of consideration of
      autolysis of mycelia at the centre of larger pellets in which growth was limited
      by diffusion of nutrients. Attempts to incorporate autolysis into the model
      improved prediction of biomass concentration but were not based on sound
      biological assumptions and increased the complexity of the model. Further
      experimental work is required for accurate description of the effects of
      autolysis on pellet growth.

PMID- 8868440
TI  - Propionyl-CoA carboxylase from Streptomyces coelicolor A3(2): cloning of the gene
      encoding the biotin-containing subunit.
AB  - In Streptomyces coelicolor A3(2), polyketides are made from malonyl-CoA, which is
      presumed to be derived from acetyl-CoA by the action of acetyl-CoA carboxylase
      (ACC). No ACC activity was found in cell-free extracts of S. coelicolor. However,
      propionyl-CoA carboxylase (PCC) activity was detected at substantial levels.
      Fixation of CO2 by ACC and PCC occurs by covalent bonding of CO2 to a biotin
      containing protein. Most bacteria have a single small biotinylated protein of
      approximately 22 kDa, but S. coelicolor contains three larger biotin-containing
      proteins (approximately 145, 88 and 70 kDa). To determine which biotinylated
      protein was associated with PCC activity, the enzyme was purified and shown to
      comprise an alpha subunit (biotin-containing) of 88 kDa and a beta subunit of 66
      kDa. The N-terminal sequences of these proteins were determined and, using an
      oligonucleotide probe, the gene for the alpha subunit (pccA) was cloned.

PMID- 8868441
TI  - Cloning, sequencing and disruption of a bromoperoxidase-catalase gene in
      Streptomyces venezuelae: evidence that it is not required for chlorination in
      chloramphenicol biosynthesis.
AB  - Genomic DNA libraries of Streptomyces venezuelae ISP5230 and of a mutant blocked
      at the chlorination step of chloramphenicol biosynthesis were probed by
      hybridization with a synthetic oligonucleotide corresponding to the N-terminal
      amino acid sequence of a bromoperoxidase-catalase purified from the wild-type
      strain. Hybridizing fragments obtained from the two strains were cloned and
      sequenced. Analysis of the nucleotide sequences demonstrated that the fragments
      contained the same 1449 bp open reading frame with no differences in nucleotide
      sequence. The deduced polypeptide encoded 483 amino acids with a calculated M(r)
      of 54,200; the N-terminal sequence was identical to that of the bromoperoxidase
      catalase purified from wild-type S. venezuelae. Comparison of the amino acid
      sequence predicted for the cloned bromoperoxidase-catalase gene (bca) with
      database protein sequences showed a significant similarity to a group of
      prokaryotic and eukaryotic catalases, but none to other peroxidases or
      haloperoxidases. Replacement of the bca gene in the wild-type strain of S.
      venezuelae with a copy disrupted by insertion of a DNA fragment encoding
      apramycin resistance did not prevent chloramphenicol production. The results
      suggest that the role of the enzyme in S. venezuelae is related to its activity
      as a catalase rather than as a halogenating agent.

PMID- 8868442
TI  - The rRNA operons of Mycobacterium smegmatis and Mycobacterium tuberculosis:
      comparison of promoter elements and of neighbouring upstream genes.
AB  - Mycobacterium smegmatis has two rRNA (rrn) operons designated rrnAf and rrnBf.
      Appropriate restriction fragments of genomic DNA containing sequences immediately
      upstream from the 16S rRNA genes were cloned. We now report the nucleotide
      sequence of 552 bp upstream from the 5'-end of the Box AL antitermination element
      of the leader region of the rrnAf operon. The 5'-end of this segment of DNA was
      found to comprise 113 codons of an ORF encoding a protein which is significantly
      similar to UDP-N-acetylglucosamine 1-carboxyvinyl-transferase (EC 2.5.1.7), which
      is important to cell wall synthesis. A homologous ORF is located immediately
      upstream from the single rrn (rrnAs) operons of Mycobacterium tuberculosis and
      Mycobacterium leprae. Primer-extension analysis of the RNA fraction of M.
      smegmatis revealed four products which were related to transcription start
      points; the rrnBf operon appears to have a single promoter whereas the rrnAf
      operon has three (P1, P2 and P3). Analysis of M. tuberculosis RNA revealed two
      products corresponding to transcripts directed by promoters homologous with P1
      and P3 of the rrnAf of M. smegmatis. Thus, the promoter and upstream regions of
      the rrnAf operon of M. smegmatis and the rrnAs operon of M. tuberculosis are
      homologous. The presence of P2 in M. smegmatis and its absence from M.
      tuberculosis is attributable to insertions/deletions of 97 bp.

PMID- 8868443
TI  - A protein having similarity with methylmalonyl-CoA mutase is required for the
      assimilation of methanol and ethanol by Methylobacterium extorquens AM1.
AB  - A 4.0 kb region of Methylobacterium extorquens AM1 DNA which complements three
      mutants unable to convert acetyl-CoA to glyoxylate (and therefore defective in
      the assimilation of methanol and ethanol) has been isolated and sequenced. It
      contains two ORFs and the 3'-end of a third one. The mutations in all three
      mutants mapped within the first ORF, which was designated meaA; it encodes a
      protein having similarity with methylmalonyl-CoA mutase. However, methylmalonyl
      CoA mutase was measured in extracts of one of the mutants and the specific
      activity was found to be similar to that in extracts of wild-type cells.
      Furthermore, although the predicted meaA gene product has the proposed cobalamin
      binding site, it does not contain a highly conserved sequence (RIARNT) which is
      present in all known methylmalonyl-CoA mutases; meaA may therefore encode a novel
      vitamin-B12-dependent enzyme. The predicted polypeptide encoded by the second ORF
      did not have similarity with any known proteins. The partial ORF encoded a
      protein with similarity with the 3-oxoacyl-[acyl-carrier-protein] reductases; it
      was not essential for growth on methanol or ethanol.

PMID- 8868445
TI  - Exclusion of long heterologous insertions and deletions from the pairing synapsis
      in pneumococcal transformation.
AB  - We have studied the mode of recombination of six insertions during genetic
      transformation of Streptococcus pneumoniae. The six heterologous insertions are
      located at the same site in the ami locus of the pneumococcal chromosome;
      insertion sizes range from 4 to 1374 bp. With respect to single-point markers we
      found that the number of transformants in one-point crosses is reduced, while the
      number of wild-type transformants in two-point crosses is drastically increased,
      what we call hyper-recombination. The magnitude of the shift is correlated with
      the size of the insert. This effect could result either from a special repair
      pathway of multibase heteroduplexes or from the exclusion of multibase
      heterologous insertions out of the pairing synapsis. To test these hypotheses we
      have used insertions in two kinds of three-point crosses. The repair model
      predicts that the excess of wild-type transformants remains in one set of crosses
      but is suppressed in the second set. The results we obtained are reversed, ruling
      out the hypothesis of a repair process, but in agreement with predictions based
      on the exclusion model. Moreover, we have re-examined the situation of deletions,
      our previous results suggesting that deletions were likely to be converted at the
      heteroduplex step. Genetic evidence we obtained in this work no longer supports
      this hypothesis. Thus, long heterologous insertions are partly excluded at the
      pairing step.

PMID- 8868444
TI  - The homologous regulators ANR of Pseudomonas aeruginosa and FNR of Escherichia
      coli have overlapping but distinct specificities for anaerobically inducible
      promoters.
AB  - The anaerobic transcriptional regulator ANR induces the arginine deiminase and
      denitrification pathways in Pseudomonas aeruginosa during oxygen limitation. The
      homologous activator FNR of Escherichia coli, when introduced into an anr mutant
      of P. aeruginosa, could functionally replace ANR for anaerobic growth on nitrate
      but not for anaerobic induction of arginine deiminase. In an FNR-positive E. coli
      strain, the ANR-dependent promoter of the arcDABC operon, which encodes the
      enzymes of the arginine deiminase pathway, was not expressed. To analyse
      systematically these distinct induction patterns, a lacZ promoter-probe, broad
      host-range plasmid containing various -40 regions (the ANR/FNR recognition
      sequences) and -10 promoter sequences was constructed. These constructs were
      tested in P. aeruginosa and in E. coli expressing either ANR or FNR. In
      conjunction with the consensus -10 hexamer of E. coli sigma 70 RNA polymerase
      (TATAAT), the consensus FNR site (TTGAT ..... ATCAA) was recognized efficiently
      by ANR and FNR in both hosts. By contrast, when promoters contained the Arc box
      (TTGAC .... ATCAG), which is found in the arcDABC promoter, or a symmetrical
      mutant FNR site (CTGAT .... ATCAG), ANR was a more effective activator than was
      FNR. Conversely, an extended 22 bp, fully symmetrical FNR site allowed better
      activation with FNR than with ANR. Combination of the arc promoter -10 sequence
      (CCTAAT) with the Arc box or the consensus FNR site resulted in good ANR
      dependent expression in P. aeruginosa but gave practically no expression in E.
      coli, suggesting that RNA polymerase of P. aeruginosa differs from the E. coli
      enzyme in -10 recognition specificity. In conclusion, ANR and FNR are able to
      activate the RNA polymerases of P. aeruginosa and E. coli when the -40 and -10
      promoter elements ae identical or close to the E. coli consensus sequences.

PMID- 8868446
TI  - Characterization of lethal factor binding and cell receptor binding domains of
      protective antigen of Bacillus anthracis using monoclonal antibodies.
AB  - Lethal toxin from Bacillus anthracis is composed of protective antigen (PA) and
      lethal factor (LF). Anti-PA mAbs that neutralized lethal toxin activity, either
      in vivo or in vitro, identified three non-overlapping antigenic regions on PA.
      Two distinct antigenic regions were recognized by the four mAbs that neutralized
      lethal toxin activity by inhibiting the binding of 125I-LF to cell-bound PA.
      Mapping showed that one mAb, 1G3PA63, recognized an epitope on a 17 kDa fragment
      located between amino acid residues Ser-168 and Phe-314. The three other mAbs,
      2D3PA, 2D5PA and 10D2PA, recognized an epitope between amino acids Ile-581 and
      Asn-601. A single antigenic region was recognized by the three mAbs, 3B6PA,
      14B7PA and 10E10PA63, that inhibited binding of 125I-PA to cells. This region was
      located between amino acids Asp-671 and Ile-721. These results confirm previously
      defined functional domains of PA and suggest that LF may interact with two
      different sites on PA to form lethal toxin.

PMID- 8868447
TI  - Progress in understanding the phylogeny of flagellates.
AB  - Heterotrophic free-living flagellates appear to provide the ancestry for all
      other eukaryote groups. Not only are the oldest surviving anaerobic eukaryotes
      flagellated protists, but also there appear to be survivors of a lineage of
      flagellate forms which could have been close to the sources of the main branches
      of eukaryote evolution. These 'stem' forms of flagellates developed more complex
      flagellation with anchoring fibres which became the main components of the
      cytoskeleton and supported the cytostome; by their phagotrophic activities these
      flagellates established symbiotic relationships, first with aerobic bacteria to
      form mitochondria, and later with various forms of prokaryotic and eukaryotic
      algal cells to form chloroplasts of a variety of types having different pigments,
      different structure and different food storage patterns. The specific patterns of
      flagellation, cytoskeleton, cytostome, secreted surface structures and cell
      aggregation into colonies enable groups of organisms to be recognised, whose most
      primitive survivors in almost all cases are heterotrophic flagellates. The
      current view of the phylogeny of eukaryotes suggests that heterotrophic
      flagellates have provided the origins of all major eukaryote groups, and that the
      phylogeny of these flagellates is the key to understanding the evolution of all
      eukaryotes. We anticipate that further rRNA analyses, supported by
      ultrastructural data, will confirm the central role played by these flagellates
      in eukaryote evolution.

PMID- 8868448
TI  - Zooflagellate phylogeny and classification.
AB  - Zooflagellates are non-photosynthetic flagellates without plastids or cell walls
      which feed by phagocytosis or endocytosis. They are the most diverse of all
      eukaryotes and gave rise directly or indirectly to most, if not all, other groups
      of eukaryotes. They are here classified into thirteen or fourteen phyla, spread
      across four of the seven eukaryote kingdoms that I now recognize: (1) the
      probably primitively amitochondrial and entirely non-photosynthetic Archezoa; (2)
      the usually aerobic but predominantly non-photosynthetic Protozoa; (3) the always
      aerobic and usually photosynthetic Cryptista; (4) the always aerobic and
      predominantly photosynthetic Chromista. Whether the few non-photosynthetic
      haptophytes also lack plastids and thus are zooflagellates in the present sense
      is unclear. Six phyla (Archamoebae and Metamonada within the Archezoa;
      Percolozoa, Parabasala, Opalozoa, and Choanozoa within the Protozoa) consist
      largely or entirely of zooflagellates. One protozoan phylum (Euglenozoa) consists
      predominantly of zooflagellate families and genera, with a minority only of
      phytoflagellate genera: the photosynthetic euglenoids are probably all descended
      from a non-photosynthetic euglenoid which acquired a photosynthetic endosymblont
      related to the ancestor of green algae. In the phylum Dinozoa (i.e.
      dinoflagellates and protalveolates) most classes consist purely of
      zooflagellates, but the majority of species are photosynthetic. The
      photosynthetic chlorarachneans are related to the sarcomonad zooflagellates and
      to the filose amoebae, so that the classes Chlorarachnea and Sarcomonadea are now
      placed in the phylum Rhizopoda, which is also modified by segregating the lobose
      amoebae as the phylum Amoebozoa. Although most zooflagellates are primitively
      without photosynthesis, there is good molecular evidence for the secondary origin
      of the zooflagellate condition by the loss of plastids in the case of the
      colourless pedinellids. A classification of 62 orders including zooflagellates
      grouped into 36 classes consisting primarily of zooflagellates, and four classes
      containing a few zooflagellates is presented; the ultrastructural and molecular
      evidence for the phylogenetic ideas underlying the classification is summarized.

PMID- 8868449
TI  - The position of flagellated protists in the system of lower eukaryotes.
AB  - The division of Eukaryota into 8 kingdoms united into 3 superkingdoms is briefly
      discussed with the rejection of the hypothesis of symbiogenesis and of primary
      nature of the dinokaryon. It is asserted that Pascher's main hypothesis remains
      valid. The heterotrophic flagellated and amoeboid forms must be included into
      different groups of flagellated beings. Some of them: Saprolegniomycetes,
      Hyphochytridiomycetes, Slopalinata, Cryptaxohelid Heliozoa have been already put
      into chromophytan branch. Others differ from autotrophic groups more sharply and
      their taxonomic position may be stated now only tentatively and will be specified
      as a result of future studies.

PMID- 8868450
TI  - Comparative morphology of kinetoplastids.
AB  - The common structural plan of bodonids, cryptobiids and trypanosomatids permits
      placing them in one phylum Kinetoplastidae. Analysis of evolutionary changes in
      the initial "bodonid" structural plan in separate groups within the
      Kinetoplastidae, illustrated by an evolutionary series of homologous characters,
      enables us to conclude that the cryptobiids occupy an intermediate position in
      kinetoplastid evolution between the free-living bodonids and Trypanosoma spp from
      lower vertebrates and can be considered to be potential ancestors of the latter.

PMID- 8868451
TI  - [The enigma of Kaposi sarcoma].
AB  - The epidemiology of AIDS-associated Kaposi's sarcoma (KS) points to a sexually
      transmittable disease. Despite the fact that a recently discovered new
      herpesvirus has been detected in all forms of KS (Aids, classic, african and
      immunosuppressed--KS) its role remains to be further established, since a simple
      infection cannot account for all epidemiologic findings in KS. Various cytokines
      seem to play an important role also. The effect of human chorionic gonadotropin
      on KS can explain the different incidence of KS in males and females. Whether all
      forms of KS indeed have common causes, today, seems doubtful.

PMID- 8868452
TI  - [Rare variants of cutaneous T-cell lymphomas].
AB  - Besides the classical forms of cutaneous T-cell lymphoma (C-CTCL), such as
      mycosis fungoides and Sezary's syndrome, unique variants may be encountered. The
      classification of these rare cutaneous T cell lymphomas is problematic and
      controversial. Newer classifications of lymphoma in general, such as the Revised
      European-American Lymphoma (REAL) Classification, emphasize well-established
      clinico-pathological entities. It seems appropriate to attempt to bring greater
      clarity to the classification of cutaneous T-cell lymphomas using the same
      principles. In this review, we list and characterize the rare variants of
      cutaneous T-cell lymphoma, such as (1) clinical, histological and immunological
      variants of mycosis fungoides; (2) progressive cutaneous T-cell lymphoma (P-CTCL)
      including transformed classical cutaneous T-cell lymphoma (TC-CTCL) and primary
      progressive cutaneous T-cell lymphoma (PP-CTCL); (3) angiocentric and
      angioimmunoblastic cutaneous T-cell lymphomas; (4) large cell anaplastic, CD30+
      cutaneous T-cell lymphoma; (5) HTLV-I-associated adult T-cell leukemia/lymphoma
      (ATLL); (6) cutaneous manifestations of primary extracutaneous T-cell neoplasias;
      (7) unclassifiable cutaneous T-cell lymphoma.

PMID- 8868453
TI  - [Association of chronic urticaria with Helicobacter pylori-induced antrum
      gastritis].
AB  - In spite of its high incidence, not much is known about the etiology of chronic
      urticaria. We performed gastroscopic evaluation of 10 patients in whom no cause
      for chronic urticaria had been found. In 8 of these 10 patients, Helicobacter
      pylori was identified in the gastric mucosa. The chronic urticarial lesions
      disappeared within a few days after starting therapy with amoxicillin and
      omeprazol.

PMID- 8868454
TI  - [Dysplastic nevus in differential epiluminescence microscopy diagnosis of
      melanoma].
AB  - The utility of two different epiluminescence microscopy rating protocols were
      tested prospectively and retrospectively on a group of 115 photographically
      documented naevi. Initially all naevi were classified histologically as
      dysplastic. While the first score table was set up only to identify dysplastic
      naevi, the second system lent itself to the differential diagnosis of malignant
      melanoma. Using this second scoring table 3 lesions were identified as melanomas
      directly and in 3 further melanomas the suspicion of dysplasia was confirmed.
      Malignancy was definitely confirmed only by histology. With regard to the surface
      microscopic differentiation of melanocytic lesions, the term "dysplasia" should
      not be abandoned. If the diagnosis of melanocytic tumours is problematic a double
      check of the clinical photograph using specific criteria cougled with
      histological evaluation appears helpful.

PMID- 8868455
TI  - [Therapeutic experiences with extracorporeal photopheresis. Technical procedure,
      follow-up and clinical outcome in 31 skin diseases].
AB  - Extracorporeal photophoresis (ECP), a therapeutic modality that has been under
      investigation for some years, is based on separation of a leucocyte/lymphocyte
      enriched cell fraction from the peripheral blood, extracorporeal treatment of the
      cells with 8-MOP/UVA and subsequent reinfusion of the cells in the patient. Its
      main effects seem to consist in changes to the immunologic behaviour of the
      photoinactivated/modulated cells. The immune response of the host is obviously
      stimulated by this treatment. ECP is normally performed for 4 h per day on 2
      consecutive days every 4 weeks. The treatment is well tolerated and causes few
      side effects. In our department, 1210 ECP treatments were administered to 41
      patients between 1990 and 1994 and a preliminary evaluation was performed. These
      patients included 21 with cutaneous T-cell lymphoma (CTCL), 10 with progressive
      systemic scleroderma, 4 with chronic graft-versus-host disease and 1 each with
      pemphigus vulgaris, epidermolysis bullosa acquisita, lupus erythematosus and
      cutaneous mucinosis. Patients with erythroderma and preserved immunocompetence
      achieved the best responses of all patients with CTCL. A treatment combining ECP
      with rIFN-alpha, PUVA and/or radiation was also successful in patients with
      tumour-stage CTCL and lymph node involvement. Progressive systemic scleroderma
      responded in more than 50% of our cases. Treatment results were impressive in 4
      patients with chronic graft-versus-host disease presenting with sclerodermatous
      and lichenoid changes of the skin and mucous membranes. A clear improvement was
      also observed in the patient with pemphigus vulgaris refractory to standard
      therapies and in another patient with scleromyxoedema (Arndt-Gottron syndrome).
      The effectiveness of ECP seems to be quite well established in CTCL, but remains
      to be examined in autoimmune dermatoses. ECP is an attractive addition to the
      dermatological therapies available but our experience is still preliminary.

PMID- 8868456
TI  - [Interferon-alpha-induced psoriasis vulgaris].
AB  - In recent years, interferon-alpha has become widely used for systemic therapy of
      tumours and infectious diseases. Well-known cutaneous side effects include dry
      skin, pruritus and hair loss. Since 1986, 17 patients with renal cell carcinoma,
      malignant melanoma, hepatitis B and C, carcinoid syndrome and hairy cell leukemia
      have been reported in whom psoriasis with or without psoratic B joint involvement
      was induced or exacerbated by systemic interferon-alpha therapy. In these
      patients, the drug was discontinued because of the severity of the psoriatic
      symptoms induced. The psoriatic lesions then resolved in nearly all patients
      within 2 weeks to 6 months, but in 10 of 22 patients treated with interferon
      alpha specifically for psoriasis exacerbation was reported. We report three new
      cases of interferon-alpha-induced psoriasis. The patients were treated with the
      drug for HIV-associated Kaposi's sarcoma, renal cell carcinoma, and hepatitis C.
      We conclude that interferon-alpha can provoke psoriatic skin and joint symptoms,
      especially when additional precipitating factors are involved. In patients in
      whom such risks are present careful consideration of the benefit/risk ratio and
      concomitant antipsoriatic treatment are essential if interferon-alpha therapy is
      to be continued.

PMID- 8868457
TI  - [Dermatitis papulosa juvenilis].
AB  - Juvenile papular dermatosis is characterized by hypopigmented lichenoid flat
      papules with predilection for the dorsa of the hands, the elbows and the knees.
      The disease affects children in the summer months. Changes observed in biopsy
      specimens show hyperkeratosis, a moderate degree of acanthosis and a lymphocytic
      perivascular infiltrate in the upper dermis. The pathogenetic influence of such
      rough materials as sand and wool and of photosensitivity in atopic patients is
      suggested. We report on a 9-year-old boy who developed lesions of juvenile
      papular dermatitis (especially severe on the face and the back of the knee) and
      extreme pruritus for the first time in summer 1994.

PMID- 8868458
TI  - [Successful topical administration of cyclosporin A in pyoderma gangraenosum].
AB  - Therapy of pyoderma gangrenosum can be complicated by side effects of the various
      systemic therapies, including corticosteroids, azathioprin and cyclosporin A. In
      this paper we report on a 49-year-old patient presenting with recalcitrant
      pyoderma gangrenosum who was treated successfully by topical application of
      cyclosporin A. Cyclosporin A serum levels were always in the subtherapeutic
      range, and no side effects were observed.

PMID- 8868459
TI  - [Clinical fluconazole and itraconazole resistance of oro-gastrointestinal
      candidiasis in a patient with AIDS].
AB  - We report on a 32-year-old male patient with advanced acquired immunodeficiency
      syndrome (AIDS), who had severe candidiasis of the gastrointestinal tract.
      Treatment with fluconazole, 200 mg/day, was introduced. After oral intake of
      fluconazole over 5 months itraconazole 200 mg/day was given for 1 month. However,
      fungal infection still persisted. The antifungal activity of fluconazole,
      itraconazole and ketoconazole against Candida albicans was evaluated by means of
      the microdilution test by determining the 90% inhibitory concentration of each
      drugs. A high minimal inhibitory concentration (MIC) was detected for fluconazole
      (50 micrograms/ml) revealing fluconazole resistance. The susceptibility to
      itraconazole was borderline (MIC 0.125 micrograms/ml) and that to ketoconazole
      was markedly lowered (MIC 0.25 micrograms/ml). Plasma levels of itraconazole were
      also found to be lowered. In HIV patients the gastrointestinal absorption of
      azole derivatives is often reduced. Therefore, the clinical resistance of Candida
      albicans to itraconazole can be explained by reduced susceptibility after azole
      therapy and also by the decreased absorption of the drug in HIV patients.

PMID- 8868460
TI  - [The scars of Andy Warhol].
AB  - The biographical and artistic documents describing to the attempted assassination
      of the artist Andy Warhol are reviewed. The visible scars are interpreted as
      symbols of the damaged integrity of the skin.

PMID- 8868461
TI  - [Granuloma annulare disseminatum as a rare side effect of allopurinol].

PMID- 8868462
TI  - [Applications of electron microscopy in dermatology].

PMID- 8868463
TI  - [Anti-inflammatory and immunosuppressive effect of glucocorticoids. What are the
      basic molecular mechanisms?].

PMID- 8868464
TI  - Inefficient growth arrest in response to dNTP starvation stimulates gene
      amplification through bridge-breakage-fusion cycles.
AB  - Cells often acquire resistance to the antiproliferative agents methotrexate (MTX)
      or N-phosphonacetyl-L-aspartate (PALA) through amplification of genes encoding
      the target enzymes dihydrofolate reductase or carbamylphosphate
      synthetase/aspartate transcarbamylase/dihydroorotase (CAD), respectively. We
      showed previously that Syrian hamster BHK cells resistant to selective
      concentrations of PALA (approximately 3 x ID50) arise at a rate of approximately
      10(-4) per cell per generation and contain amplifications of the CAD gene as
      ladder-like structures on one of the two B9 chromosomes, where CAD is normally
      located. We now find that BHK cells resistant to high concentrations of PALA
      (approximately 15 x ID50) appear only after prior exposure to selective
      concentrations of PALA for approximately 72 h. Furthermore, in contrast to
      untreated cells, BHK cells pretreated with selective concentrations of MTX give
      colonies in high concentrations of PALA, and cells pretreated with selective
      concentrations of PALA give colonies in high concentrations of MTX or 5
      fluorouracil. As judged by measuring numbers of cells and metaphase cell pairs,
      BHK cells do not arrest completely when starved for pyrimidine nucleotides by
      treatment with selective concentrations of PALA for up to 72 h. We propose that
      DNA damage, caused when cells fail to stop DNA synthesis promptly under
      conditions of dNTP starvation, stimulates amplification throughout the genome by
      mechanisms--such as bridge-breakage-fusion cycles--that are triggered by broken
      DNA. Amplified CAD genes were analyzed by fluorescence in situ hybridization both
      in cells where amplification was induced by PALA pretreatment and in cells in
      which the amplification occurred spontaneously, before selection with PALA. The
      ladder-like structures that result from bridge-breakage-fusion cycles were
      observed in both cases.

PMID- 8868465
TI  - Wortmannin alters the transferrin receptor endocytic pathway in vivo and in
      vitro.
AB  - Treatment with the phosphatidylinositol 3-kinase inhibitor wortmannin promotes
      approximately 30% decrease in the steady-state number of cell-surface transferrin
      receptors. This effect is rapid and dose dependent, with maximal down-regulation
      elicited with 30 min of treatment and with an IC50 approximately 25 nM
      wortmannin. Wortmannin-treated cells display an increased endocytic rate constant
      for transferrin internalization and decreased exocytic rate constants for
      transferrin recycling. In addition to these effects in vivo, wortmannin is a
      potent inhibitor (IC50 approximately 15 nM) of a cell-free assay that detects the
      delivery of endocytosed probes into a common compartment. Inhibition of the in
      vitro assay involves the inactivation of a membrane-associated factor that can be
      recruited onto the surface of vesicles from the cytosol. Its effects on the cell
      free assay suggest that wortmannin inhibits receptor sorting and/or vesicle
      budding required for delivery of endocytosed material to "mixing" endosomes. This
      idea is consistent with morphological changes induced by wortmannin, which
      include the formation of enlarged transferrin-containing structures and the
      disruption of the perinuclear endosomal compartment. However, the differential
      effects of wortmannin, specifically increased transferrin receptor
      internalization and inhibition of receptor recycling, implicate a role for
      phosphatidylinositol 3-kinase activity in multiple sorting events in the
      transferrin receptor's membrane traffic pathway.

PMID- 8868466
TI  - A distinct basic fibroblast growth factor (FGF-2)/FGF receptor interaction
      distinguishes urokinase-type plasminogen activator induction from mitogenicity in
      endothelial cells.
AB  - Basic fibroblast growth factor (FGF-2) induces cell proliferation and urokinase
      type plasminogen activator (uPA) production in fetal bovine aortic endothelial GM
      7373 cells. In the present paper we investigated the role of the interaction of
      FGF-2 with tyrosine-kinase (TK) FGF receptors (FGFRs) in mediating uPA up
      regulation in these cells. The results show that FGF-2 antagonists suramin,
      protamine, heparin, the synthetic peptide FGF-2(112-155), and a soluble form of
      FGFR-1 do not inhibit FGF-2-mediated uPA up-regulation at concentrations that
      affect growth factor binding to cell surface receptors and mitogenic activity. In
      contrast, tyrosine phosphorylation inhibitors and overexpression of a dominant
      negative TK- mutant of FGFR-1 abolish the uPA-inducing activity of FGF-2,
      indicating that FGFR and its TK activity are essential in mediating uPA
      induction. Accordingly, FGF-2 induces uPA up-regulation in Chinese hamster ovary
      cells transfected with wild-type FGFR-1, -2, -3, or -4 but not with TK- FGFR-1
      mutant. Small unilamellar phosphatidyl choline:cholesterol vesicles loaded with
      FGF-2 increased uPA production in GM 7373 cells in the absence of a mitogenic
      response. Liposome-encapsulated FGF-2 showed a limited but significant capacity,
      relative to free FGF-2, to interact with FGFR both at 4 degrees C and 37 degrees
      C and to be internalized within the cell. uPA up-regulation by liposome
      encapsulated FGF-2 was quenched by neutralizing anti-FGF-2 antibodies, indicating
      that the activity of liposome-delivered FGF-2 is mediated by an extracellular
      action of the growth factor. Taken together, the data indicate that a distinct
      interaction of FGF-2 with FGFR, quantitatively and/or qualitatively different
      from the one that leads to mitogenicity, is responsible for the uPA-inducing
      activity of the growth factor.

PMID- 8868468
TI  - Purification and identification of FOAD-II, a cytosolic protein that regulates
      secretion in streptolysin-O permeabilized mast cells, as a rac/rhoGDI complex.
AB  - Mast cells permeabilized by treatment with streptolysin-O in the presence of Ca2+
      and GTP-gamma-S can secrete almost 100% of their contained N-acetyl-beta-D
      glucosaminidase. If these stimuli are provided to the permeabilized cells after a
      delay, the response is diminished and the ability of the cells to undergo
      secretion runs down progressively over a period of about 30 min. This is thought
      to be due to the loss of key proteins involved in the exocytotic mechanism. Using
      this effect as the basis of a biological assay, we have isolated a protein from
      bovine brain cytosol that retards the loss of responsiveness to stimulation by
      Ca2+ and GTP-gamma-S. Purification of this protein and peptide sequencing have
      enabled us to identify it as the small GTP-binding protein rac complexed to the
      guanine nucleotide exchange inhibitor rhoGDI. Both proteins are required to
      retard the loss of the secretory response, while purified rhoGDI applied alone
      accelerates the rundown.

PMID- 8868467
TI  - CD44/chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human
      melanoma cell migration on type IV collagen and invasion of basement membranes.
AB  - Tumor cell invasion of basement membranes (BM) represents one of the critical
      steps in the metastatic process. Tumor cell recognition of individual BM matrix
      components may involve individual cell adhesion receptors, such as integrins or
      cell surface proteoglycans, or may involve a coordinate action of both types of
      receptors. In this study, we have focused on the identification of a cell surface
      CD44/chondroitin sulfate proteoglycan (CSPG) and alpha 2 beta 1 integrin on human
      melanoma cells that are both directly involved in the in vitro invasion of
      reconstituted BM via a type IV collagen-dependent mechanism. Interfering with
      cell surface expression of human melanoma CSPG with either p-nitro-phenyl-beta-D
      xylopyranoside treatment or anti-CD44 monoclonal antibody (mAb) preincubation
      (mAb) preincubation inhibits melanoma cell invasion through reconstituted BM.
      These treatments also strongly inhibit melanoma cell migration on type IV
      collagen, however, they are ineffective at inhibiting cell adhesion to type IV
      collagen. Purified melanoma cell surface CD44/CSPG, or purified chondroitin
      sulfate, bind to type IV collagen affinity columns, consistent with a role for
      CD44/CSPG-type IV collagen interactions in mediating tumor cell invasion. In
      contrast, melanoma cell migration on laminin (LM) does not involve CD44/CSPG, nor
      does CD44/CSPG bind to LM, suggesting that CD44/CSPG-type IV collagen
      interactions are specific in nature. Additionally, anti-alpha 2 and anti-beta 1
      integrin mAbs are capable of blocking melanoma cell invasion of reconstituted BM.
      Both of these anti-integrin mAbs inhibit melanoma cell adhesion and migration on
      type IV collagen, whereas only anti-beta 1 mAb inhibits cell adhesion to LM.
      Collectively, these results indicate that melanoma cell adhesion to type IV
      collagen is an important consideration in invasion of reconstituted BM in vitro,
      and suggest that CD44/CSPG and alpha 2 beta 1 integrin may collaborate to promote
      human melanoma cell adhesion, migration, and invasion in vivo.

PMID- 8868469
TI  - Characterization of a novel CDC gene (ORC1) partly homologous to CDC6 of
      Saccharomyces cerevisiae.
AB  - A novel cell cycle gene was identified by a computer search for genes partly
      homologous to known CDC genes, CDC6 of Saccharomyces cerevisiae and CDC18 of
      Schizosaccharomyces pombe, using the nucleotide sequence data base for S.
      cerevisiae produced by the Yeast Sequencing Project. The protein sequence coded
      by the cloned gene was found to be identical to that of purified ORC1 protein.
      Disruption of the gene and subsequent tetrad analysis revealed that the gene was
      essential for growth. The function of the gene product was analyzed by depleting
      the protein from the cell using a mutant haploid strain containing the disrupted
      ORC1 gene on the chromosome and a galactose-inducible gene coding for HA-tagged
      ORC1 protein on a single copy plasmid. The HA-tagged protein was expressed during
      growth in the presence of galactose but began to decrease rapidly upon depletion
      of galactose. Analysis of the cell cycle progression of the mutant cells by FACS
      after the removal of galactose from the medium, and microscope observations of
      cells and their nuclei revealed that the normal progression of 2N cells was
      immediately impeded as the ORC1 protein started to decrease. This was blocked
      completely in the cells that had progressed to the S phase under conditions
      deficient in ORC1 protein followed by cell death. Two-dimensional gel analysis of
      the replication intermediates after the galactose removal revealed that the
      depletion of ORC1 protein caused a decrease in the frequency of initiation of
      chromosomal replication, eventually resulting in the inhibition of replication as
      a whole. The function of the ORC1 protein in the cell cycle progression of S.
      cerevisiae is discussed in light of current information on ORC.

PMID- 8868470
TI  - Aequorin targeted to the endoplasmic reticulum reveals heterogeneity in luminal
      Ca++ concentration and reports agonist- or IP3-induced release of Ca++.
AB  - A chimeric protein (ERaeq) comprised of the invariant chain (Ii) of class II
      major histocompatability complex (MHC-II) and aequorin was localized in the
      endoplasmic reticulum (ER) of transfected human embryonal kidney 293 cells. The
      targeted aequorin resided in the lumen of the ER membrane system, including the
      nuclear cistern, and following addition of the chromophore coelenterazine
      underwent Ca(++)-activated chemiluminescence. The majority of chemiluminescence
      produced by coelenterazine treatment of ERaeq-expressing 293 cells was consumed
      rapidly (within 2-4 min) upon re-addition of Ca++ to coelenterazine-loaded cells,
      a finding consistent with very high Ca++ concentrations (approximately 10(-5)-10(
      3) M Ca++ ion) inside the ER. However, following the initial rapid consumption of
      ERaeq chemiluminescence, the activity that remained (10-30% of total sample
      luminescence of permeabilized cells or 50-70% of total sample luminescence of
      intact cells) was found to produce a stable baseline corresponding to a Ca++ ion
      concentration < or = 1-2 microM. The stable baseline of luminescence observed
      following rapid consumption of the majority of the sample's activity was not
      derived from re-binding of fresh chromophore to spent photoprotein, suggesting
      that a minority fraction of the ER membrane system within which the ERaeq chimera
      was distributed contained a relatively low Ca++ concentration. Addition of IP3 to
      digitonin-permeabilized cells, or agonist treatment of intact cells decreased
      this residual signal. Luminescence recordings from cells expressing an ER
      targeted aequorin with relatively high affinity for Ca++ thus reveal
      heterogeneity in luminal ER Ca++ concentration and permit observation of receptor
      and IP3-activated release of Ca++ from the ER membrane system.

PMID- 8868471
TI  - Physical association of the small GTPase Rho with a 68-kDa phosphatidylinositol 4
      phosphate 5-kinase in Swiss 3T3 cells.
AB  - Our previous work showed that post-translationally modified Rho in its GTP-bound
      state stimulated phosphatidylinositol 4-phosphate 5-kinase (PIP5K) activity in
      mouse fibroblast lysates. To investigate whether Rho physically interacts with
      PIP5K, we incubated immobilized Rho-GST with Swiss 3T3 cell lysates and tested
      for retained PIP5K activity. Rho-GST, but not Ras-GST or GST alone, bound
      significant PIP5K activity. The binding of PIP5K was independent of whether Rho
      was in a GTP- or GDP-bound state. An antibody against a 68-kDa human erythrocyte
      type I PIP5K recognized a single 68-kDa protein eluted from Rho-GST column. The
      Rho-associated PIP5K responded to phosphatidic acid differentially from the
      erythrocyte type I PIP5K, suggesting that it could be a distinct isoform not
      reported previously. Rho co-immunoprecipitated with the 68-kDa PIP5K from Swiss
      3T3 lysates, demonstrating that endogenous Rho also interacts with PIP5K. ADP
      ribosylation of Rho with C3 exoenzyme enhanced PIP5K binding by approximately
      eightfold, consistent with the ADP-ribosylated Rho functioning as a dominant
      negative inhibitor. These results demonstrate that Rho physically interacts with
      a 68-kDa PIP5K, although whether the association is direct or indirect is
      unknown.

PMID- 8868472
TI  - Juvenile and mature MAP2 isoforms induce distinct patterns of process outgrowth.
AB  - Microtubule-associated protein-2 (MAP2) is the most abundant MAP in neurons,
      where its distribution is restricted to the somatodendritic compartment. This
      molecule undergoes developmentally regulated alternative splicing, resulting in
      at least two isoforms, a juvenile isoform (termed MAP2c) and a mature isoform
      (MAP2), with greatly different molecular masses. Spodoptera frugiperda (Sf9) cell
      expression of the juvenile versus the mature MAP2 isoform generates two distinct
      patterns of process outgrowth. The smaller juvenile isoform induces multiple
      short thin processes. Mature MAP2 tends to induce single processes that are
      considerably thicker than those processes induced by juvenile MAP2. We found
      important differences in the variability of spacing between microtubules and the
      number of microtubules along the processes induced by MAP2c and mature MAP2.
      MAP2c showed variability with most microtubules spaced as closely as with tau,
      but some spaced as far apart as with mature MAP2. Over their length, the mature
      MAP2 processes demonstrate proximo-distal taper, which corresponds to a narrowing
      of the spacing between microtubules from 90 nm to 40 nm. Moreover, there is a
      decreased number of microtubules in mature MAP2-induced processes whereas in tau
      and MAP2-induced processes, the number of microtubules is constant along the
      length. Based on these observations, we conclude that MAP2 isoforms can serve as
      architectural elements by establishing specific morphological features of
      processes and specific arrangements of their microtubules.

PMID- 8868473
TI  - Cell cycle control by Xenopus p28Kix1, a developmentally regulated inhibitor of
      cyclin-dependent kinases.
AB  - We have isolated Xenopus p28Kix1, a member of the p21CIP1/p27KIP1/p57KIP2 family
      of cyclin-dependent kinase (Cdk) inhibitors. Members of this family negatively
      regulate cell cycle progression in mammalian cells by inhibiting the activities
      of Cdks. p28 shows significant sequence homology with p21, p27, and p57 in its N
      terminal region, where the Cdk inhibition domain is known to reside. In contrast,
      the C-terminal domain of p28 is distinct from that of p21, p27, and p57. In co
      immunoprecipitation experiments, p28 was found to be associated with Cdk2, cyclin
      E, and cyclin A, but not the Cdc2/cyclin B complex in Xenopus egg extracts.
      Xenopus p28 associates with the proliferating cell nuclear antigen, but with a
      substantially lower affinity than human p21. In kinase assays with recombinant
      Cdks, p28 inhibits pre-activated Cdk2/cyclin E and Cdk2/cyclin A, but not
      Cdc2/cyclin B. However, at high concentrations, p28 does prevent the activation
      of Cdc2/cyclin B by the Cdk-activating kinase. Consistent with the role of p28 as
      a Cdk inhibitor, recombinant p28 elicits an inhibition of both DNA replication
      and mitosis upon addition to egg extracts, indicating that it can regulate
      multiple cell cycle transitions. The level of p28 protein shows a dramatic
      developmental profile: it is low in Xenopus oocytes, eggs, and embryos up to
      stage 11, but increases approximately 100-fold between stages 12 and 13, and
      remains high thereafter. The induction of p28 expression temporally coincides
      with late gastrulation. Thus, although p28 may play only a limited role during
      the early embryonic cleavages, it may function later in development to establish
      a somatic type of cell cycle. Taken together, our results indicate that Xenopus
      p28 is a new member of the p21/p27/p57 class of Cdk inhibitors, and that it may
      play a role in developmental processes.

PMID- 8868474
TI  - Membrane integration of in vitro-translated gap junctional proteins: co- and post
      translational mechanisms.
AB  - Connexins (Cx) are protein components of gap junction channels that permit the
      passage of small molecules between neighboring cells. cDNAs of a large family of
      connexins have been isolated and sequenced. A gap junction channel consists of
      two connexons, one from each cell in contact, composed of six connexin subunits.
      It has been suggested by Musil and coworkers that the oligomerization of
      formation of a connexon occurs at the level of the trans-Golgi network. In the
      present study, we initiated an analysis of the early stages of protein synthesis
      and membrane insertion of Cx32 and Cx26, two connexins that we have demonstrated
      are co-expressed in the same junctions in hepatocytes. Using an in vitro
      transcription and a coupled cell-free translation and translocation system, we
      observed that both Cx32 and Cx26 could insert into microsome membranes co
      translationally, producing a topological structure indistinguishable from that in
      isolated gap junctions. To our surprise, Cx26 could also insert into membranes
      post-translationally with a native orientation. This post-translational membrane
      insertion process is dependent on nucleotides but not their hydrolysis. Cx32, on
      the other hand, could not insert into membranes post-translationally. These
      disparate properties of Cx32 and Cx26 are not due to the significant difference
      in the lengths of their C-terminal domains, but rather to their internal amino
      acid sequences. These observations raise the possibility that there may be
      another pathway for Cx26 to insert into membranes in cells and this feature may
      be important for the regulation of its functions. These findings may also lead us
      to a new approach to reconstitution without detergent extraction.

PMID- 8868475
TI  - ERGIC-53 is a functional mannose-selective and calcium-dependent human homologue
      of leguminous lectins.
AB  - Based on sequence homologies with leguminous lectins, the intermediate
      compartment marker ERGIC-53 was proposed to be a member of a putative new class
      of animal lectins associated with the secretory pathway. Independent, a
      promyelocytic protein, MR60, was purified by mannose-column chromatography, and a
      cDNA was isolated that matched MR60 peptide sequences. This cDNA was identical to
      that of ERGIC-53 and homologies with the animal lectin family of the galectins
      were noticed. Not all peptide sequences of MR60, however, were found in ERGIC-53,
      raising the possibility that another protein associated with ERGIC-53 may possess
      the lectin activity. Here, we provide the first direct evidence for a lectin
      function of ERGIC-53. Overexpressed ERGIC-53 binds to a mannose column in a
      calcium-dependent manner and also co-stains with mannosylated neoglycoprotein in
      a morphological binding assay. By using a sequential elution protocol we show
      that ERGIC-53 has selectivity for mannose and low affinity for glucose and
      GlcNAc, but no affinity for galactose. To experimentally address the putative
      homology of ERGIC-53 to leguminous lectins, a highly conserved protein family
      with an invariant asparagine essential for carbohydrate binding, we substituted
      the corresponding asparagine in ERGIC-53. This mutation, as well as a mutation
      affecting a second site in the putative carbohydrate recognition domain,
      abolished mannose-column binding and co-staining with mannosylated
      neoglycoprotein. These findings establish ERGIC-53 as a lectin and provide
      functional evidence for its relationship to leguminous lectins. Based on its
      monosaccharide specificity, domain organization, and recycling properties, we
      propose ERGIC-53 to function as a sorting receptor for glyco-proteins in the
      early secretory pathway.

PMID- 8868477
TI  - A novel, multilayer structure of a helical peptide.
AB  - X-ray diffraction analysis at 1.5 A resolution has confirmed the helical
      conformation of a de novo designed 18-residue peptide. However, the crystal
      structure reveals the formation of continuous molecular layers of parallel-packed
      amphiphilic helices as a result of much more extensive helix-helix interactions
      than predicted. The crystal packing arrangement, by virtue of distinct
      antiparallel packing interactions, segregates the polar and apolar surfaces of
      the helices into discrete and well-defined interfacial regions. An extensive
      "ridges-into-grooves" interdigitation characterizes the hydrophobic interface,
      whereas an extensive network of salt bridges and hydrogen bonds dominates the
      corresponding hydrophilic interface.

PMID- 8868476
TI  - pH-Dependent self-association of the Src homology 2 (SH2) domain of the Src
      homologous and collagen-like (SHC) protein.
AB  - The Src homologous and collagen-like (SHC) protein plays an essential role in
      signal transduction pathways in that it participates in the chain of events that
      leads to the activation of the protein Ras. The crystal structure of the SH2
      domain of SHC has been determined using the method of multiple isomorphous
      replacement at a resolution of 2.5 A. The SH2 domain of SHC is similar in fold to
      other SH2 domains. The peptide-binding surfaces resemble that of the SH2 domain
      of Src in that a deep pocket is formed where the third amino acid C-terminal to
      the phosphotyrosine can insert. A novel feature of this structure is the
      observation of a disulfide bond and an extensive dimer interface between two
      symmetry-related molecules. Solution studies under reducing conditions using
      analytical centrifugation and PAGE suggest that the SH2 domain of SHC dimerizes
      in a pH-dependent manner where low pH conditions (approximately 4.5) are
      conducive to dimer formation. Dimerization of SHC may have important biological
      implications in that it may promote the assembly of large heteromultimeric
      signaling complexes.

PMID- 8868479
TI  - The structure of bovine mitochondrial adenylate kinase: comparison with
      isoenzymes in other compartments.
AB  - In vertebrates, there are different adenylate kinases in the compartments
      cytosol, mitochondrial intermembrane space, and mitochondrial matrix. Here, we
      report the spatial structure of the intermembrane species established in two
      crystal forms by X-ray diffraction analyses at 1.92 and 2.1 A resolution. In both
      structures, the enzyme is unligated, and thus in an "open" conformation. The
      enzyme was prepared from bovine liver, containing at least five variants arisen
      from posttranscriptional and posttranslational modifications. It could only be
      crystallized after removing some of these variants. A comparison with the known
      structures of the adenylate kinases from cytosol and mitochondrial matrix reveals
      structural differences that should play a role in protein targeting because none
      of these enzymes contains a cleavable signal peptide. A further comparison with
      adenylate kinases from Gram-positive bacteria showed that the structural Zn2+ ion
      of these species is replaced by a strictly conserved assembly of hydrogen bonded
      residues.

PMID- 8868478
TI  - Synthesis, structure, and structure-activity relationships of divalent thrombin
      inhibitors containing an alpha-keto-amide transition-state mimetic.
AB  - A new class of divalent thrombin inhibitors is described that contains an alpha
      keto-amide transition-state mimetic linking an active site binding group and a
      group that binds to the fibrinogen-binding exosite. The X-ray crystallographic
      structure of the most potent member of this new class, CVS995, shows many
      features in common with other divalent thrombin inhibitors and clearly defines
      the transition-state-like binding of the alpha-keto-amide group. The structure of
      the active site part of the inhibitor shows a network of water molecules
      connecting both the side-chain and backbone atoms of thrombin and the inhibitor.
      Direct peptide analogues of the new transition-state-containing divalent thrombin
      inhibitors were compared using in vitro assays of thrombin inhibition. There was
      no direct correlation between the binding constants of the peptides and their
      alpha-keto-amide counterparts. The most potent alpha-keto-amide inhibitor,
      CVS995, with a Ki = 1 pM, did not correspond to the most potent divalent peptide
      and contained a single amino acid deletion in the exosite binding region with
      respect to the equivalent region of the natural thrombin inhibitor hirudin. The
      interaction energies of the active site, transition state, and exosite binding
      regions of these new divalent thrombin inhibitors are not additive.

PMID- 8868480
TI  - Phosphorylation-induced torsion-angle strain in the active center of HPr,
      detected by NMR and restrained molecular dynamics refinement.
AB  - The structure of the phosphorylated form of the histidine-containing
      phosphocarrier protein HPr from Escherichia coli has been solved by NMR and
      compared with that of unphosphorylated HPr. The structural changes that occur
      upon phosphorylation of His 15, monitored by changes in NOE patterns, 3JNHH alpha
      coupling constants, and chemical shifts, are limited to the region around the
      phosphorylation site. The His15 backbone torsion angles become strained upon
      phosphorylation. The release of this strain during the phosphoryl-transfer to
      Enzyme II facilitates the transport of carbohydrates across the membrane. From an
      X-ray study of Streptococcus faecalis HPr (Jia Z, Vandonselaar M, Quail JW,
      Delbaere LTJ, 1993, Nature 361:94-97), it was proposed that the observed torsion
      angle strain at residue 16 in unphosphorylated S. faecalis HPr has a role to play
      in the protein's phosphocarrier function. The model predicts that this strain is
      released upon phosphorylation. Our observations on E. coli HPr in solution, which
      shows strain only after phosphorylation, and the fact that all other HPrs studied
      thus far in their unphosphorylated forms show no strain either, led us to
      investigate the possibility that the crystal environment causes the strain in S.
      faecalis HPr. A 1-ns molecular dynamics simulation of S. faecalis HPr, under
      conditions that mimic the crystal environment, confirms the observations from the
      X-ray study, including the torsion-angle strain at residue 16. The strain
      disappeared, however, when S. faecalis HPr was simulated in a water environment,
      resulting in an active site configuration virtually the same as that observed in
      all other unphosphorylated HPrs. This indicates that the torsion-angle strain at
      Ala 16 in S. faecalis HPr is a result of crystal contacts or conditions and does
      not play a role in the phosphorylation-dephosphorylation cycle.

PMID- 8868481
TI  - Mutational studies of conserved residues in the dimer interface of nerve growth
      factor.
AB  - An understanding of the structure-function relationship of nerve growth factor
      (NGF) requires precise knowledge of all the residues and regions that participate
      in NGF receptor binding, receptor activation, and biological activity. Seven
      recombinant human NGF mutants having alanine substituted for residues located
      either in the NGF dimer interface or beta-strand region were studied to determine
      the role of each amino acid residue in NGF biological activity. F86A, T91A,
      R100A, and R103A remained nearly full active with 61, 120, 91, and 73% of wild
      type activity, respectively, in the PC12 cell bioassay. Hydrophobic core and
      dimer interface residues Y52, F53, and F54 were studied in more detail. Y52A and
      F54A were expressed in very low levels, suggesting that these two residues may be
      important for protein stability. Y52A retained full biological activity (91%).
      F53A had a 20- and 70-fold reduction in biological activity and TrkA
      phosphorylation, respectively, with only a 5- to 10-fold effect on TrkA binding
      and no effect on low-affinity receptor binding. F54A had significantly decreased
      TrkA phosphorylation and biological activity (40-fold). The results suggest that
      F53 and F54 may play a structural role in TrkA receptor activation subsequent to
      binding.

PMID- 8868482
TI  - Overexpression of bacterio-opsin in Escherichia coli as a water-soluble fusion to
      maltose binding protein: efficient regeneration of the fusion protein and
      selective cleavage with trypsin.
AB  - Bacteriorhodopsin (bR) is a light-driven proton pump from Halobacterium
      salinarium and is a model system for studying membrane protein folding,
      stability, function, and structure. bR is composed of bacterio-opsin (bO), the
      248-amino acid apo protein, and all-trans retinal, which is linked to lysine 216
      via a protonated Schiff base. A bO gene (sbOd) possessing 29 unique restriction
      sites and a carboxyl-terminal purification epitope (1D4, nine amino acids) has
      been designed and synthesized. Overexpression of bO was achieved by fusion to the
      carboxyl terminus of maltose binding protein (MBP). The expressed fusion protein
      (MBP-sbO-1D4) formed inclusion bodies in Escherichia coli and, following
      solubilization with urea and removal of the urea by dialysis, approximately 170
      mg of approximately 75% pure MBP-sbO-1D4 was obtained from 1 L of culture. MBP
      sbO-1D4 formed high molecular weight (> or = 2,000 kDa) oligomers that were water
      soluble. The synthetic bO with the 1D4 tag (sbO-1D4) was separated from MBP by
      trypsin cleavage at the factor Xa site between the MBP and sbO-1D4 domains.
      Selective trypsin cleavage at the factor Xa site, instead of at the 14 other
      potential trypsin sites within bO, was accomplished by optimization of the
      digestion conditions. Both MBP-sbO-1D4 and sbO-1D4 were regenerated with all
      trans retinal and purified to homogeneity. In general, 6-10 mg of sbR-1D4 and 52
      mg of MBP-sbR-1D4 were obtained from 1 L of cell culture. No significant
      differences in terms of UV/vis light absorbance, light/dark adaptation, and
      photocycle properties were observed among sbR-1D4, MBP-sbR-1D4, and bR from H.
      salinarium.

PMID- 8868484
TI  - Influence of the GroE molecular chaperone machine on the in vitro refolding of
      Escherichia coli beta-galactosidase.
AB  - We have studied the effect of the components of the GroE molecular chaperone
      machine on the refolding of the Escherichia coli enzyme beta-galactosidase, a
      tetrameric protein whose 116-kDa promoters should not completely fit within the
      central cavity of the GroEL toroid. In the absence of other additives, GroEL
      formed a weak complex with chemically denatured beta-galactosidase, reduced its
      propensity to aggregate, and increased the recovery yields of active enzyme
      twofold without altering its folding pathway. When present together with the
      chaperonin, ATP--and to a lesser extent AMP-PNP--reduced the recovery yields and
      led to the resumption of aggregation. The use of the complete chaperonin system
      (GroEL, GroES, and ATP) eliminated the GroEL-mediated increase in recovery and
      folding proceeded less efficiently than in buffer alone. This unusual behavior
      can be explained in terms of a chaperonin "buffering" effect and the different
      affinities of GroE complexes for denatured beta-galactosidase.

PMID- 8868483
TI  - Interlobe communication in multiple calcium-binding site mutants of Drosophila
      calmodulin.
AB  - We have generated mutants of Drosophila calmodulin in which pairs of calcium
      binding sites are mutated so as to prevent calcium binding. In all sites, the
      mutation involves replacement of the -Z position glutamate residue with
      glutamine. Mutants inactivated in both N-terminal sites (B12Q) or both C-terminal
      sites (B34Q), and two mutants with one N- and one C-terminal site inactivated
      (B13Q and B24Q) were generated. The quadruple mutant with all four sites mutated
      was also studied. UV-difference spectroscopy and near-UV CD were used to examine
      the influence of these mutations upon the single tyrosine (Tyr-138) of the
      protein. These studies uncovered four situations in which Tyr-138 in the C
      terminal lobe responds to a change to the calcium-binding properties of the N
      terminal lobe. Further, they suggest that N-terminal calcium-binding events
      contribute strongly to the aberrant behavior of Tyr-138 seen in mutants with a
      single functional C-terminal calcium-binding site. The data also indicate that
      loss of calcium binding at site 1 adjusts the aberrant conformation of Tyr-138
      produced by mutation of site 3 toward the wild-type structure. However,
      activation studies for skeletal muscle myosin light chain kinase (SK-MLCK)
      established that all of the multiple binding site mutants are poor activators of
      SK-MLCK. Thus, globally, the calcium-induced conformation of B13Q is not closer
      to wild type than that of either the site 1 or the site 3 mutant. The positioning
      of Tyr-138 within the crystal structure of calmodulin suggests that effects of
      the N-terminal lobe on this residue may be mediated via changes to the central
      linker region of the protein.

PMID- 8868485
TI  - Electrospray mass spectrometric investigation of the chaperone SecB.
AB  - Electrospray ionization mass spectrometry was used to investigate the structure
      of the Escherichia coli chaperone protein SecB. It was determined that the N
      terminal methionine of SecB has been removed and that more than half of all SecB
      monomers are additionally modified, most likely by acetylation of the N-terminus
      or a lysine. The use of gentle mass spectrometer interface conditions showed that
      the predominant, oligomeric form of SecB is a tetramer that is stable over a
      range of solution pH conditions and mass spectrometer interface heating (i.e.,
      inlet capillary temperatures). At very high pH, SecB dimers are observed. SecB
      contains a region that is hypersensitive to cleavage by proteinase K and is
      thought to be involved in conformational changes that are crucial to the function
      of SecB. We identified the primary site of cleavage to be between Leu 141 and Gln
      142. Fourteen amino acids are removed, but the truncated form remains a tetramer
      with stability similar to that of the intact form.

PMID- 8868486
TI  - Three-dimensional solution structure of the HIV-1 protease complexed with DMP323,
      a novel cyclic urea-type inhibitor, determined by nuclear magnetic resonance
      spectroscopy.
AB  - The three-dimensional solution structure of the HIV-1 protease homodimer, MW 22.2
      kDa, complexed to a potent, cyclic urea-based inhibitor, DMP323, is reported.
      This is the first solution structure of an HIV protease/inhibitor complex that
      has been elucidated. Multidimensional heteronuclear NMR spectra were used to
      assemble more than 4,200 distance and angle constraints. Using the constraints,
      together with a hybrid distance geometry/simulated annealing protocol, an
      ensemble of 28 NMR structures was calculated having no distance or angle
      violations greater than 0.3 A or 5 degrees, respectively. Neglecting residues in
      disordered loops, the RMS deviation (RMSD) for backbone atoms in the family of
      structures was 0.60 A relative to the average structure. The individual NMR
      structures had excellent covalent geometry and stereochemistry, as did the
      restrained minimized average structure. The latter structure is similar to the
      1.8-A X-ray structure of the protease/DMP323 complex (Chang CH et al., 1995,
      Protein Science, submitted); the pairwise backbone RMSD calculated for the two
      structures is 1.22 A. As expected, the mismatch between the structures is
      greatest in the loops that are disordered and/or flexible. The flexibility of
      residues 37-42 and 50-51 may be important in facilitating substrate binding and
      product release, because these residues make up the respective hinges and tips of
      the protease flaps. Flexibility of residues 4-8 may play a role in protease
      regulation by facilitating autolysis.

PMID- 8868488
TI  - A stable intermediate in the thermal unfolding process of a chimeric 3
      isopropylmalate dehydrogenase between a thermophilic and a mesophilic enzymes.
AB  - The thermal unfolding process of a chimeric 3-isopropylmalate dehydrogenase made
      of parts from an extreme thermophile, Thermus thermophilus, and a mesophile,
      Bacillus subtilis, enzymes was studied by CD spectrophotometry and differential
      scanning calorimetry (DSC). The enzyme is a homodimer with a subunit containing
      two structural domains. The DSC melting profile of the chimeric enzyme in 20 mM
      NaHCO3, pH 10.4, showed two endothermic peaks, whereas that of the T.
      thermophilus wild-type enzyme had one peak. The CD melting profiles of the
      chimeric enzyme under the same conditions as the DSC measurement, also indicated
      biphasic unfolding transition. Concentration dependence of the unfolding profile
      revealed that the first phase was protein concentration-independent, whereas the
      second transition was protein concentration-dependent. When cooled after the
      first transition, the intermediate was isolated, which showed only the second
      transition upon heating. These results indicated the existence of a stable
      dimeric intermediate followed by the further unfolding and dissociation in the
      thermal unfolding of the chimeric enzyme at pH 10-11. Because the portion derived
      from the mesophilic isopropylmalate dehydrogenase in the chimeric enzyme is
      located in the hinge region between two domains of the enzyme, it is probably
      responsible for weakening of the interdomain interaction and causing the
      decooperativity of two domains. The dimeric form of the intermediate suggested
      that the first unfolding transition corresponds to the unfolding of domain 1
      containing the N- and C-termini of the enzyme, and the second to that of domain 2
      containing the subunit interface.

PMID- 8868487
TI  - On the entropy of protein folding.
AB  - The failure to appreciate that the hydration of polar groups is a major
      contribution to the entropy of protein unfolding has led to considerable
      underestimates for the loss of configurational freedom when a protein chain
      folds.

PMID- 8868489
TI  - Control of aggregation in protein refolding: the temperature-leap tactic.
AB  - The kinetics of renaturation of bovine carbonic anhydrase II (CAII) were studied
      from 4 degrees to 36 degrees, at the relatively high [CAII] of 4 mg/mL. Following
      dilution to 1 M guanidinium chloride, aggregate formation is very rapid and
      reduces the formation of active enzyme. The CAII activity yield at 150 min, 20
      degrees (approximately 60%), is greater than that at either 4 degrees or 36
      degrees. However, if refolding is conducted at 4 degrees, aggregation is reduced
      dramatically and 37% yield is obtained at 120 min. If the solution is then
      rapidly warmed to 36 degrees, the yield rises rapidly to 95% at 150 min. This is
      an example of the "temperature leap" tactic. These results can be understood on
      the basis of two slow-folding intermediate whose kinetics have been studied. Only
      the first of these forms aggregates. Kinetic simulations show that, at 4 degrees,
      the first intermediate is depleted after 120 min, and the second intermediate
      rapidly isomerizes to active enzyme on warming. A series of experiments was
      conducted where the initial (120 min) folding temperature was systematically
      varied, followed by a "leap" to 36 degrees for 30 additional minutes. With
      initial incubations from 4 degrees to 12 degrees, the final yield is > 90%, drops
      rapidly from 12 degrees to 20 degrees, and decreases more gradually to
      approximately 45% at 36 degrees. The overall results qualitatively fit the simple
      idea of ordinary temperature-accelerated reactions in competition with
      hydrophobic aggregation, which is strongly suppressed in the cold. Qualifications
      are discussed for the temperature-leap approach to find application in refolding
      other proteins.

PMID- 8868490
TI  - Mass spectrometric-based revision of the structure of a cysteine-rich peptide
      toxin with gamma-carboxyglutamic acid, TxVIIA, from the sea snail, Conus textile.
AB  - A mollusk-specific toxin, TxVIIA, having potent paralytic activity was isolated
      from the venom of sea snail Conus textile (Fainzilber M et al., 1991, Eur J
      Biochem 202:589-595). The structure reported above was based upon amino acid
      analysis and the Edman degradation. We have recently reinvestigated this toxin
      employing some of the most novel techniques in mass spectrometry. We now report a
      revised structure based primarily on high-energy collision-induced dissociation
      analysis of the two Asp17-N peptides of the reduced, pyridinylethyl derivative
      representing the entire sequence using matrix-assisted laser desorption
      ionization (MALDI) as CGGYSTYC gamma VDS gamma CCSDNCVRSYCTLF-NH2 (gamma, gamma
      carboxyglutamic acid or Gla). The N-terminus of the previous sequence was
      incorrect, apparently due to a side reaction of reduction and alkylation, which
      led to the erroneous assignment of Trp for the N-terminal residue. In addition,
      the last two C-terminal amino acids and the C-terminal amidation had not been
      detected. Also, a combination of electrospray ionization mass spectrometry and
      positive and negative ion MALDI mass spectrometry provided information on the
      molecular weights of the native and derivatized toxin and presence of two Gla
      residues. Thus, TxVIIA does not have an "unusual" sequence as previously
      reported, but in fact belongs to the conserved Cys framework for omega- and delta
      conotoxins. However, the four net negative charges with the cysteine-rich
      structure of this revised sequence is highly unusual for conopeptides.

PMID- 8868491
TI  - Ca(2+)-binding domain VI of rat calpain is a homodimer in solution: hydrodynamic,
      crystallization and preliminary X-ray diffraction studies.
AB  - The 21-kDa calcium-binding domain (VI) of the small subunit of rat calpain II has
      been expressed in Escherichia coli, purified, and crystallized. Two orthorhombic
      crystal forms have been obtained: space group P2(1)2(1)2(1) with a = 50.3, b =
      56.5, c = 141.3 A; and space group C222(1) with a = 69.4, b = 73.9, c = 157.4 A.
      Diffraction data have been collected to 2.4 A. Sedimentation equilibrium, dynamic
      light scattering, and gel-permeation chromatography indicate that domain VI
      exists as a homodimer in solution. In accordance with the protein's behavior in
      solution, each crystal form contains two molecules per asymmetric unit. Screening
      for heavy-atom derivatives is in progress. To decrease the sensitivity to
      mercurials and to aid in the search for useful derivatives, Cys-to-Ser mutants
      have been prepared, expressed, and crystallized.

PMID- 8868492
TI  - Crystallization and preliminary diffraction studies of NodL, a rhizobial O-acetyl
      transferase involved in the host-specific nodulation of legume roots.
AB  - The NodL specified O-acetyltransferase from the microbial symbiont Rhizobium
      leguminosarum has been over-expressed in Escherichia coli and purified using
      affinity-elution dye chromatography as the key step. The protein has been
      crystallized at 20 degrees C in 18% PEG 600, 0.1 M Tris/HCl buffer, pH 8.5,
      containing 1% dioxane, 0.25% octyl-beta-glucoside, and 5 mM coenzyme A using the
      hanging drop vapor diffusion method. Ambient temperature X-ray diffraction
      studies reveal the space group to be hexagonal (P6(3)22) with lattice constants a
      = b = 77.08 A, c = 160.6 A, and alpha = beta = 90 degrees, gamma = 120 degrees.
      Crystals that are flash-frozen to 120 K diffract beyond 2.7 A.

PMID- 8868493
TI  - A large compressibility change of protein induced by a single amino acid
      substitution.
AB  - The adiabatic compressibility (beta s) was determined, by means of the precise
      sound velocity and density measurements, for a series of single amino acid
      substituted mutant enzymes of Escherichia coli dihydrofolate reductase (DHFR) and
      aspartate aminotransferase (AspAT). Interestingly, the beta s values of both DHFR
      and AspAT were influenced markedly by the mutations at glycine-121 and valine-39,
      respectively, in which the magnitude of the change was proportional to the enzyme
      activity. This result demonstrates that the local change of the primary structure
      plays an important role in atomic packing and protein dynamics, which leads to
      the modified stability and enzymatic function. This is the first report on the
      compressibility of mutant proteins.

PMID- 8868494
TI  - Legal protection or legal threat? Ethical conflicts in the process of medical
      decision making.
AB  - Children have a fundamental right to good health care. It seems natural that they
      should be treated according to their age and intellectual capacity. However, this
      is more complicated than it seems at first and causes ethical conflicts. This
      article discusses whether Dutch and European law can solve these ethical
      conflicts and points out that solutions are not always to be found through legal
      interference, which may lead to judicial paternalism.

PMID- 8868496
TI  - Sexual orientation of parents and Dutch family law.
AB  - A few years ago, the Dutch government asked for advice about the legal
      consequences of various living arrangements. One of the main issues concerned the
      legal consequences thereof for children. In a letter to parliament, the Dutch
      cabinet confirmed that couples of the same sex would be excluded from being
      awarded children for adoption. Legal and psychological reasons play an important
      role in the reasoning of the Dutch government. The harmonious development of
      children is supposed to be at risk when the child is reared by two adults of the
      same sex. This article sets out psychological theories and the results of recent
      research which contradict the argumentation presented in a number of recent
      reports published by the government. The outcome of most research is that gay and
      lesbian parents 'perform' as well as heterosexual parents. Excluding lesbian and
      gay parents from taking responsibility for children seems to be a poor policy
      which does not take into account the social capacities of the population.

PMID- 8868495
TI  - The uncertain 'best interests' of neonates: decision making in the neonatal
      intensive care unit.
AB  - Neonatology is a recently specialized area of medicine in which medical advances
      continue to save the lives of many ailing infants. However, like most areas of
      health care, it is not a perfect science, and hence not all infants can be saved,
      no matter how advanced the technology or how well-trained the physician.
      Inevitably, decisions regarding when to forego treatment must be made. It is
      essential to scrutinize the bases upon which these decisions are reached. This
      article examines the development of the scientific, legal and philosophical
      theories in Canada, the United States and the United Kingdom in an attempt to
      delineate a nexus wherein these theories link together to found medical decisions
      in the neonatal intensive care unit. Legal rules of medical decision making are
      informed by standards set by the medical profession as well as by principles of
      moral philosophy. However, in the face of medical uncertainty regarding outcomes,
      the content of the 'best interests' of the child standard increasingly relies
      upon a normative conception of the 'sanctity of life'. Ironically, as science
      pushes at the bounds of the meaning of 'medical futility', the sanctity of life
      position gains strength and is relied upon more frequently by the judiciary. The
      author concludes that both subjective and objective factors must inform this
      decision making in order to protect the best interests of the child optimally.

PMID- 8868497
TI  - Embryo experimentation and the murder prohibition: a casuistic examination of the
      utilitarian and pro-life positions on the moral status of the embryo.
AB  - Argument concerning the permissibility of embryo experimentation has tended to
      proceed from the opposed ethical principles of utilitarianism and the sanctity of
      human life, neither of which entirely reflects Western society's present position
      on murder and moral obligations. Singer's utilitarian arguments propose a test of
      subject attributes for admission to the protection of morality, and it is argued
      that this approach is entirely at odds with our current axiomatic application of
      the murder prohibition of post-birth humans. Similarly, those arguing from a pro
      life position do not take account of the ambivalence of our application of this
      principle to the pre-birth human, as seen in abortion. In the attempt to deal
      with the quandary of the moral position of the embryo, we should, following the
      philosophical precedent of casuistry, start from the position of our current
      moral certainties, rather than expose ourselves to the social dangers of an
      untried rationality divorced from practice.

PMID- 8868498
TI  - The limitations of intimate samples in sexual offences.
AB  - This article reviews the problems of sampling and interpretation of scientific
      findings from samples taken by doctors during their examination of victims and
      suspects in sexual offences. The problems which may be encountered with vaginal,
      anal, oral and penile swabs are highlighted. These include contamination between
      samples and the consequences thereof. The responsibilities of the medical
      examiner, the investigating police officer and the scientist are stressed.
      Surveys of results stored in a database and case examples are used to illustrate
      the problems.

PMID- 8868499
TI  - Legislating to preserve women's autonomy during pregnancy.
AB  - Women are often excluded from the process of medical decision making during
      pregnancy, even though medical decisions that are made by health care
      professionals affect them personally and affect the future well-being of the
      unborn. Women in general and pregnant women in particular, will feel the impact
      of new genetic tests and technologies, designed to predict and even treat certain
      genetic problems during pregnancy, through prenatal diagnosis, foetal surgery and
      foetal gene therapy. This may be the first of several implications that new
      genetics technologies will hold for women's autonomy during pregnancy. Does
      genetic testing of a foetus empower women or pose an unanticipated threat to
      autonomy? To address these issues, there is a need to articulate a feminist
      perspective on genetic testing and possibly to legislate protection of women's
      rights during prenatal care. This article raises, but does not answer, several
      important issues regarding the implications of new developments in genetic
      testing that will affect pregnant women's autonomy in medical decision making.
      The article concludes that, although there are United States constitutional
      protections for the right to abortion and in turn, therapeutic abortion, an
      unfavourable chain of precedents regarding women's autonomy during pregnancy
      makes it imperative that there be strong legislation providing assurances that
      information will be given to pregnant women about the genetic testing process;
      that women will be made aware of their right to refuse treatment; that the law
      will require health care professionals to give adequate information to pregnant
      women regarding possible treatment outcomes in order to make an informed choice;
      and that there will be adequate protection for the right to confidentiality of
      information regarding prenatal prognosis, in order to safeguard autonomous
      decision making during pregnancy.

PMID- 8868500
TI  - Liability risks in gynaecology and obstetrics under German and Austrian law.
AB  - This article discusses various aspects of criminal and civil liability with
      special reference to Austrian and German law. Whereas there are already
      innumerable German court decisions covering gynaecological and obstetric practice
      this is not yet true for Austria. However, the basic legal structure in both
      legal systems is very similar. Therefore German court practice which is
      progressively adopting a very strict liability regime could be influential for
      Austria's judiciary as well.

PMID- 8868501
TI  - Towards the practice of surrogacy in Israel.
AB  - This article discusses the prohibition of surrogacy in Israeli subordinate
      legislation and the illegality and unconstitutionality of this prohibition. It
      reviews the recommendations of a public committee appointed to investigate the
      practice of surrogacy and the applicability of adoption laws to children born of
      surrogate arrangements. In view of the growing demand for access to surrogacy and
      the need to resolve the problem of childlessness in Israel, the author recommends
      the enactment of primary legislation to regulate the matter.

PMID- 8868502
TI  - Informed consent and disclosure in the physician-patient relationship: expanding
      obligations for physicians in the United States.
AB  - In recent years, the doctrine of informed consent has been one of the primary
      vehicles by which American courts and legislatures have evaluated the nature and
      scope of information that physicians must disclose to patients in a variety of
      treatment situations. Historically, physicians have had the primary
      responsibility to disclose to patients the nature of a proposed course of
      treatment, material risks and benefits, as well as reasonably available
      alternatives, in obtaining consent to treatment. Statutory and common-law
      developments in the United States appear to suggest that disclosure obligations
      of physicians in this context are continuing to evolve. This article examines
      recent judicial and legislative developments in the United States, which appear
      to underlie expanding disclosure obligations in a variety of situations that
      arise within the context of the physician-patient relationship. Emphasis is
      placed on disclosure obligations with respect to the physician's physical
      condition and its impact on the provision of medical care, information regarding
      the physician's general ability to perform certain surgeries or other medical
      procedures, as well as disclosure of research interests, financial interests, and
      other incentives that may bear upon clinical decision making. This article
      concludes that physicians should be aware of recent statutory and common-law
      developments in the United States that may give rise to heightened potential for
      legal accountability arising out of failure to disclose an increasingly diverse
      array of information to patients in the physician-patient relationship.

PMID- 8868503
TI  - DNA profiling: 'insurmountable proof' or exaggeration?
AB  - DNA profiling is currently the most novel technique utilized in family law and
      criminal matters where the identity or identification of an individual is in
      dispute. Its recognized potential, as a tool for identification, is phenomenal.
      In the light of the overwhelming acceptance of the test and the results yielded
      by both the popular and professional press, a mantle of almost mystic
      infallibility fell over the evidence provided by DNA typing in many courtrooms
      across the world. Fortunately, in certain jurisdictions, the naturally enquiring
      mind of man reasserted itself and legal brains began to recognize a potential for
      error in the test procedures and results. Thus emerged the challenge to the
      notion of absolute reliability and trustworthiness of the test findings. To date,
      as several cases indicate, these results have already been successfully disputed,
      ensuring the acquittal of accused who, in the early days, would have had only
      little hope of success.

PMID- 8868504
TI  - Medical negligence in a developing country.
AB  - This article reviews medical malpractice in developing black African countries in
      the context of the limitations and constraints placed on professional practice in
      these countries. Financial, infrastructural, educational, cultural, religious,
      political and historical factors all play a crucial role in the provision of
      health care, and societal values are reflected in patients' expectations
      regarding acceptable professional performance and the liability of doctors for
      medical negligence.

PMID- 8868505
TI  - Involuntary hospitalization and the rights of mental patients in Croatia.
AB  - In Croatia, a 1934 law still prescribes that all hospitals are obliged to inform
      the court of jurisdiction of the involuntary hospitalization of mental patients.
      The court, after conducting its own inquiry, has to decide whether the continued
      detention of the patient is justified or whether he or she should be discharged.
      In practice, however, this law is violated, because some psychiatrists are not
      aware of it and because others deliberately choose to ignore it, considering
      involuntary hospitalization to be an exclusively medical issue to be solved
      within the medical profession. From the point of view of the protection of the
      basic human rights of mental patients, especially their right to freedom, and in
      the interests of general legal certainty, the present situation is most
      unsatisfactory. This article analyses how this unacceptable practice came about
      and recommends how it should be changed.

PMID- 8868507
TI  - Psychiatric hospitalization of senile and arteriosclerotic dementia patients by
      commitment order under the 1991 Israeli Mental Health Act.
AB  - Data regarding commitment orders issued by district psychiatrists for elderly
      patients aged 65 years or older were obtained from the national psychiatric case
      register. Out of a total of 2,284 commitment orders issued in Israel in the
      period 1 January 1992 to 30 June 1993 under the 1991 Mental Health Act, 191
      (8.3%) involved patients aged 65 and over; these orders were issued for the
      commitment of 169 patients who suffered from the following ICD-9-CM diagnoses on
      discharge: senile and arteriosclerotic dementia; transient organic psychotic
      conditions; schizophrenic disorders; affective psychoses; paranoid states; or
      other psychiatric disorders. Demographic and clinical characteristics of the
      senile and arteriosclerotic dementia patients were compared with the same
      variables in the other diagnostic categories. Results showed that (a) involuntary
      commitment of senile and arteriosclerotic dementia patients involved a small
      minority of dementia sufferers; (b) it was usually the patients' first
      psychiatric admission; (c) most of the patients were discharged within a one
      month period; and (d) most of the patients were referred for continuation of
      treatment in non-psychiatric institutions. Findings (c) and (d) characterized
      other diagnostic categories as well. The relevance of these findings to the
      Mental Health Act is discussed.

PMID- 8868506
TI  - Halachic perspective on involuntary psychiatric care of the mentally ill.
AB  - According to most mental health statutes in force around the world, doctors may
      involuntarily treat only acutely psychotic patients who present some danger to
      themselves, others or property. Chronic patients who, owing to volitional or
      cognitive defects, present a similar danger may not be thus treated. This may
      cause situations to arise where dangerous chronically ill patients who refuse
      treatment may cause serious harm because of physicians' inability to treat them.
      This article suggests changes to contemporary mental health statutes, in line
      with Judaic Halachic codes, which view all mentally ill patients as potentially
      harmful, and require physicians to treat--voluntarily or involuntarily--all
      mentally ill persons.

PMID- 8868508
TI  - Legal status of persons with chronic mental illness admitted to psychiatric
      hospitals.
AB  - Psychiatric patients have been, and continue to be, victims of social rejection,
      a phenomenon that has led to their de facto marginalization. The historical
      evolution of Western society has been characterized by a tendency to move from
      laws that preferentially protect society from a perceived threat from individuals
      with mental illness towards laws intended to protect and defend the interests of
      these individuals. The spirit of the current legislative framework is to protect
      persons with mental illness and to guarantee the protection of each and every one
      of their rights. However, it should be recognized that promulgation of a new law
      is not tantamount to its enforcement. The purpose of this study was to
      investigate the actual legal status of persons admitted to psychiatric hospitals.

PMID- 8868509
TI  - Dog as detective.

PMID- 8868510
TI  - Poor correlation between soluble fibrin concentrations measured by two
      commercially available immunoassays.
AB  - Soluble fibrin (SF) has attracted considerable interest as a marker for
      haemostatic activation. Two new enzyme immunoassays for SF, Enzymun-Test FM
      (Boehringer Mannheim, Germany) and Fibrinostika Soluble Fibrin (Organon Teknika,
      Belgium) have recently become commercially available. We measured plasma levels
      of SF in clinically obtained blood samples in order to compare the two new
      assays. Blood was drawn from 10 healthy volunteers and from 149 patients on the
      first day after surgery for fractures of the upper part of the femur. Collection
      and processing was done according to the manufacturers' recommendations. In the
      patients, levels found by the two assays were significantly different. The
      Enzymun-Test assay reported a median (range) of 11.87 (2.66 - > 62.20) mg/l,
      whereas the Fibrinostika assay found a median (range) of 3.34 (1.08 - >10) mg/l.
      The correlation coefficient was 0.38 (Spearman). A poor correlation was thus
      found between values obtained by the two assays in the patient category chosen.
      Further validation of the assays is necessary.

PMID- 8868511
TI  - Low molecular weight heparin and the heparin mobilisable pool of platelet factor
      4 are reduced in young survivors of myocardial infarction.
AB  - The platelet factor 4 (PF4) mobilisation properties of low molecular weight
      heparin (Fraxiparine, Sanofi Winthrop, France) in young survivors of myocardial
      infarction (YSMI) and healthy volunteers have been investigated. The study group
      consisted of 42 YSMI less than 44 years old, all of them with angiographically
      proven occlusive coronary artery disease, studied 6 to 24 months after the acute
      event. The control group was composed of 30 healthy men of similar age. Subjects
      from the study and control groups were allocated to the following subgroups:
      those receiving 60 or 120 IU/kg b.w. of standard heparin (Polfa Kutno, Poland)
      and those receiving 60, 120 or 180 IC anti-Xa U/kg b.w. of low molecular weight
      heparin (Fraxiparine, Sanofi Winthrop, France) as a single intravenous injection.
      Additionally, in five YSMI patients the influence of prolonged aspirin
      administration (0.3g daily for more than 30 days) on the Fraxiparine mobilsable
      pool of PF4 and beta-thromboglobulin (beta-TG) concentration in the plasma was
      determined after injection of 180 IC anti-Xa U/kg b.w. of the drug. The PF 4 and
      beta-TG concentration in the plasma was evaluated using enzyme immunoassay
      methods before heparin or Fraxiparine intravenous injection and 2, 5, 10, 20, 30
      and 60 min after. In both, the control and YSMI groups baseline PF4 levels were
      found to be normal. Moreover, similar marked dose-dependent increases of PF4
      concentration in the plasma measured after 60 and 120 IU/kg b.w. of heparin as
      well as after 60 and 120 IC anti-Xa U/kg b.w. of Fraxiparine was found. The
      administration of 120 IU/kg b.w. of heparin resulted in a reduced rise in plasma
      PF 4 in YSMI as compared to healthy controls. The same phenomenon was observed
      when 180 IC anti-Xa U/kg b. w. of Fraxiparine was injected intravenously. In YSMI
      treatment with aspirin had no influence on the Fraxiparine mobilisable pool of PF
      4 or the beta-TG concentration in the plasma. These results suggest that
      mobilisable pool of platelet factor 4 in young survivors of myocardial infarction
      derives from the "nonplatelet pool" and that reduction of heparin- or Fraxiparine
      releasable pool of PF4 may reflect an impaired endothelium function, probably due
      to atherosclerosis.

PMID- 8868512
TI  - On the occurrence of thrombin-like enzymes in mosquitoes.
AB  - A thrombin-like enzyme has been identified in mosquitoes and partially purified.
      The enzyme preparation displays on SDS gel electrophoresis a major protein band
      of about 22 kDa and one minor of about 28 kDa. The enzyme preparation cleaves a
      synthetic substrate (S-2238) for thrombin with Km 113 mumol/L (as compared to 3
      mumol/L for thrombin). The enzyme clots fibrinogen and plasma. During activation
      of fibrinogen, fibrinopeptide A (but scarcely fibrinopeptide B) is released. The
      enzyme is not inhibited by hirudin and activates (if at all) factor XIII
      differently from thrombin. Predominantly gamma-dimers are formed in the cross
      linking process. As compared to thrombin a larger extent of activation is
      required to induce gelation (clotting) by the mosquito enzyme. At a given
      clotting time the enzyme produces tighter gel structures than thrombin. In its
      action the enzyme resembles the snake venom enzyme, batroxobin.

PMID- 8868513
TI  - Hirudin stimulates prostacyclin but not endothelin-1 production in cultured human
      vascular endothelial cells.
AB  - To study the effect of hirudin on endothelial cell prostacyclin (PGI2) and
      endothelin-1 (ET-1) production, we cultured human umbilical vein endothelial
      cells (HUVECs), stimulated them with 0.00001-10 kU/l of hirudin for 12-24 hours,
      and measured by radioimmunoassays the concentrations of 6-ketoprostaglandinF1
      alfa (6-keto, a metabolite of PGI2) and ET-1 in the incubation medium. In
      incubation medium containing 10% serum hirudin stimulated PGI2-production dose
      dependently. The lowest stimulatory hirudin concentration was 0.001 kU/l, which
      increased the concentration of 6-keto by 10.8 +/- 4.4% (mean +/- S.E) (p < 0.01).
      The greatest stimulation rate (28.6 +/- 6.2%, p < 0.001) was obtained with the
      highest hirudin concentration (10 kU/l), when the culture medium contained 10%
      human serum. The PGI2-stimulating activity was exaggerated in the absence of
      serum, when 1 kU/l of hirudin increased PGI2-production by 59.7 +/- 6.2% (p <
      0.001, n = 14). Stimulation of PGI2 appeared after 12 hour incubation. Hirudin
      had no effect on the conversion of exogenous arachidonic acid to 6-keto or on the
      production of ET-1. We thus conclude that hirudin stimulates PGI2-production
      through de novo protein synthesis. Stimulation of PGI2-production by hirudin may
      contribute to its antithrombotic activity, since PGI2 favours vasodilatation and
      attenuates platelet aggregation.

PMID- 8868514
TI  - Platelets of patients with peripheral arterial disease are hypersensitive to
      heparin.
AB  - We sought to verify earlier reports of increased platelet reactivity in patients
      with peripheral arterial disease (PAD) during perioperative heparin
      administration, and to test the hypothesis of platelet hypersensitivity to
      heparin in these patients. Before and after incubation of platelet rich plasma
      with unfractionated (UH), low molecular weight heparin (LMWH), and a low
      molecular weight heparinoid, real-time quantitative assessment of platelet
      function was performed by stagnation point flow adhesio-aggregometry (SPAA) in 21
      patients with PAD and 14 healthy volunteers. With SPAA the occurrence of
      spontaneous aggregation is pathological. In the 15 patients requiring operation,
      platelet function and count were measured at regular intervals. To detect heparin
      dependent antibodies, the heparin induced platelet activation assay (HIPA) was
      performed preoperatively and after 10 days of heparin therapy. Mean baseline
      platelet adhesion in patients was double that observed in controls (p < 0.001).
      Spontaneous aggregation was seen in 9 (43%) patients and no controls (p < 0.001).
      In controls heparinoid reduced, whereas UH and LMWH slightly increased adhesion.
      Spontaneous aggregation was observed once with UH. Platelets from patients showed
      significantly enhanced adhesiveness and aggregability (p < 0.05) with UH and LMWH
      when compared to controls. Effects with the heparinoid were less pronounced and
      non-significant. In patients requiring operation, postoperative increases in
      platelet function and reductions in count were significant (p < 0.001). Ten (67%)
      experienced a fall in platelet count of > 50%. Preoperatively the HIPA assay
      showed no evidence of antibodies, whereas after heparin administration antibodies
      were verified in 4 (32%) patients and could not be ruled out in 6 (40%). Three
      developed postoperative thrombosis, in one case fatal. A hypersensitive in vitro
      and in vivo platelet response to heparin was verified in patients with PAD and a
      large number developed the immunological type of heparin-associated
      thrombocytopenia. Our findings suggest that a thrombin antagonist which does not
      interact with platelets may give the best perioperative protection in these
      patients.

PMID- 8868515
TI  - Flush heparin during cardiac catheterisation prevents long-term coagulation
      activation in children without APC-resistance-preliminary results.
AB  - This study was designed to prospectively evaluate haemostatic activation in 75
      children undergoing cardiac catheterisation with intermittent flush heparin (10
      IU/ml saline) and to relate these data to clinical findings and inherited risk
      factors for thrombophilia. In addition to flush heparin in infants < 6 months of
      age in whom additional arterial catheterisation was performed (n = 5) or patients
      with thrombophilia, heparin (300-400 IU/kg/d) was administered for a further 24
      h. APTT was prolonged and anti Xa activity was significantly increased at the end
      of catheterisation and returned to normal 24 hours later. Whereas thrombin
      generation (F1 + 2) showed a significant coagulation activation at the end of
      catheterisation, no concomitant fibrinolytic activation (D-Dimer) was observed.
      Four children showed resistance to APC: one of them in whom stroke had occurred
      before and one additional child heterozygous for APCR received further
      prophylactic heparin. Two neonates with APCR and flush heparin only suffered from
      thrombosis after catheterisation. No further thrombotic events occurred. This
      study indicates that low-dose flush heparin during catheterisation may prevent
      long-term haemostatic activation in children without thrombophilia. Whether
      further heparin after cardiac catheterisation in children with APCR prevents
      vascular insults requires a more intensive study.

PMID- 8868516
TI  - Factor VII binding to tissue factor in plasma from warfarin-treated individuals.
AB  - Using enzyme immunoassay, we measured the binding ability of artificial gamma
      carboxyglutamic acid (Gla)-domainless-Factor VII (FVII) to tissue factor (TF) or
      of Factor VII in 44 patients stabilized by long term treatment with warfarin.
      Purified FVII digested with cathepsin G, that is Gla-domainless-FVII, showed a
      rapid loss in the binding ability of FVII to TF (FVII-TF binding). After
      adsorption with Al(OH)3 of plasma from 8 out of 44 warfarin-treated patients, no
      FVII clotting activity (FVII:c) was detected in the supernatant, whereas FVII
      antigen (FVII:ag) and FVII-TF binding remained 19.2% and 17%, respectively, as
      compared with those before adsorption. In the plasma from 44 warfarin-treated
      patients the FVII:c (mean +/- SD, 54.26 +/- 12.50%) was significantly lower than
      the FVII:ag (77.15 +/- 18.24%) (p < 0.001), although the FVII:c was significantly
      correlated with FVII:ag (r = 0.628). FVII-TF binding (68.27 +/- 21.16%) was
      significantly higher than FVII:c (p < 0.001), but not than FVII:ag (p > 0.05).
      The FVII-TF binding was significantly correlated with FVII:ag (r = 0.738), but
      somewhat poorly with FVII:c (r = 0.415). These results show that artificial Gla
      domainless-FVII digested with cathepsin G loses both the clotting activity and
      the binding ability to TF. However, PIVKA-VII has little or no clotting activity
      but the binding ability to TF. This suggested that the low specific activity of
      FVII (FVII:c/FVII:ag) in the plasma of warfarin-treated patients would not
      entirely depend on the decreased FVII-TF binding.

PMID- 8868517
TI  - APC resistance in neonates and infants: adjustment of the APTT-based method.
AB  - Resistance to activated protein C (APCR) has emerged as the most important
      hereditary cause of venous thromboembolism. Using an aPTT-based method together
      with DNA technique we investigated 120 healthy neonates and infants < 12 months
      of age and 24 infants with septicaemia for the presence of this mutation. In
      addition, data of 11 neonates with vascular occlusion, heterozygous (+/-) for the
      Arg 506 Gln mutation were included. Results of an aPTT-based method (clotting
      time using the APC/CaCl2 solution obtained in an undiluted, 1:5 and 1:11 dilution
      with factor V deficient plasma divided by clotting time with CaCl2 in the same
      plasma dilution) are shown: Whereas 7 (5.5%) out of 120 healthy neonates were (+/
      ) carriers for the factor V Arg 506 Gln mutation, concordance with the aPTT-based
      method (cut-off defined as ratio < 2) was found only when using the 1:11 plasma
      dilution. Six (four) out of 24 infants with sepsis, not carrying the factor V
      mutation, would have been classified as APC resistant when using the 1:1 (1:5)
      plasma dilution. Four (two) out of 18 patients, (+/-) for the Arg 506 Gln
      mutation showed APC ratios > 2 in the 1:1(1:5) plasma dilution.

PMID- 8868518
TI  - Tissue factor pathway inhibitor (TFPI) activity in uremic patients during
      hemodialysis.
AB  - We studied tissue factor pathway inhibitor (TFPI) activity during hemodialysis in
      10 uremic patients who were not receiving anticoagulant for at least 120 minutes.
      TFPI activity before dialysis was normal (patients 107 +/- 5.8%, controls 104 +/-
      4.5%). During extracorporeal circuit it rose progressively with a statistically
      significant difference, reaching a plateau between 60 and 120 minutes. Since
      thrombin induces a marked redistribution and release of TFPI from stimulated
      endothelial cells and platelets contain about 10% of TFPI activity that is
      secreted following activation it is possible that thrombin-induced release of
      TFPI by endothelium and platelets could account for the increased TFPI we found
      during hemodialysis. To investigate this possibility we measured during dialysis
      beta-thromboglobulin (beta-TG), thrombin-antithrombin complex (TAT) and
      prothrombin fragment 1.2 (F 1.2). The increased levels of beta-TG, TAT and F1.2
      we noted during extracorporeal circuit are in keeping with this concept. One
      hundred eighty minutes after initiation of dialysis, by which time all patients
      were receiving heparin there was a further increase in TFPI (to more than 200% of
      baseline), due to the presence of the glycosaminoglycan. This was due the
      previously reported displacement by heparin of the major intravascular pool of
      TFPI, from endothelial cell surfaces.

PMID- 8868519
TI  - Expression of human platelet glycoprotein Ib beta in insect cells.

PMID- 8868520
TI  - Recurrent restenosis after percutaneous transluminal coronary angioplasty in a
      patient with congenital protein C deficiency and high activated factor VII level.

PMID- 8868521
TI  - Antiphospholipid antibodies and disturbances of phospholipid dependent
      coagulation tests in patients with systemic sclerosis and severe peripheral
      ischaemia.

PMID- 8868522
TI  - Design of alpha-helical peptides: their role in protein folding and molecular
      biology.

PMID- 8868523
TI  - Cell growth and differentiation from the perspective of dynamical organization of
      cellular and subcellular processes.

PMID- 8868524
TI  - Mammalian cutaneous mechanoreceptors.

PMID- 8868526
TI  - [History and definition of sepsis--do we need new terminology?].
AB  - The history of sepsis demonstrates that despite current knowledge about its
      pathogenesis the definition of sepsis is more contested than ever. However, a
      definite terminology is necessary to define the entrance criteria for future
      clinical studies concerning patients with sepsis or septic shock. For this
      purpose, in 1991 a consensus conference was held in the US, but its
      recommendations have not found unequivocal acceptance. These recommendations and
      their historical background are presented and their consequences discussed.

PMID- 8868525
TI  - [New muscle relaxants].
AB  - Mivacurium is a short-acting nondepolarising muscle relaxant of the
      benzylisoquinoline type undergoing rapid breakdown by plasma cholinesterase. With
      2.5 fold ED95, tracheal intubation can be accomplished within 2-3 min following
      injection. The ensuing DUR 25% (i.e. time from injection to 25% recovery of
      control twitch tension) is three times as long as with succinylcholine and about
      half as long as with equipotent doses of atracurium and vecuronium. The principal
      side effects of mivacurium are facial flushing and a transient fall in blood
      pressure due to a moderate histamine release following doses of 3-4 times the
      ED95. In patients with end stage liver or renal disease as well as in patients
      with atypical plasma cholinesterase the duration of action of mivacurium is
      prolonged. Rocuronium is a steroidal non-depolarising neuromuscular blocking
      agent chemically related to vecuronium. Compared with the latter, rocuronium is
      less potent, has a shorter onset of action, and no cumulative effects. Adequate
      intubating conditions are achieved within 60 to 90 s after i.v. injection of
      twice the ED95. Its elimination from the blood occurs primarily via liver uptake,
      while renal elimination is about 10 to 30%. Slight vagolytic effects are reported
      following injection of 0.6 mg/kg rocuronium, while histamine release is unlikely
      to occur. Atracurium is a mixture of ten stereoisomers. One of them, cis
      atracurium, is five times as potent as the chiral mixture while having a similar
      pharmacodynamic and kinetic profile. It does not cause significant histamine
      release or clinically relevant cardiovascular effects at doses up to 8 times the
      ED95. Laudanosine release seems to be less with cis-atracurium than with
      atracurium.

PMID- 8868527
TI  - [Neuromuscular and cardiovascular effect of mivacurium in anesthesia induction in
      patients with renal failure].
AB  - OBJECTIVE: Mivacurium produces a prolonged neuromuscular block (NMB) in anuric
      patients (13), in spite of its rapid hydrolysis by pseudocholinesterase (PChE)
      which is independent of renal function (17). In the present study the
      pharmacodynamics and the cardiovascular effects of a bolus dose of mivacurium
      (0.15 mg/kg) in relation to impairment of renal function were evaluated. METHODS:
      60 patients (ASA class 2-4) were assigned to one of three groups according to the
      degree of renal dysfunction. Creatinine clearance (Krea-Cl) as a measure of renal
      function was calculated using weight, age, sex and serum creatinine
      concentrations. Group C (control): Krea-Cl > 50 ml/min; group P (preterminal): 20
      ml/min < Krea-Cl < 50 ml/min; group T (terminal): Krea-Cl < 20 ml/min. PChE
      activity and dibucaine numbers were assessed preoperatively. Neuromuscular
      transmission (Train-of-Four) was monitored using electromyography (Relaxograph,
      Datex Inc.) with stimulation of the ulnar nerve. The response was recorded from
      the hypothenar muscle. Five minutes after induction of anaesthesia with propofol
      and fentanyl, 0.15 mg/kg mivacurium was given i.v. over 30 s. 150 s later
      patients were intubated. Anaesthesia was maintained by propofol (2-10 mg/kg/h)
      and fentanyl (0-5 micrograms/kg/h) infusion. Patients were ventilated with
      oxygen/nitrous oxide (FiO2 = 0.35). As soon as T1 recovered to 5% or more,
      mivacurium was administered continuously and this part of the study was finished.
      Times of onset (onset 10; onsetmax), maximal neuromuscular block (NMBmax),
      neuromuscular block when intubation was started (NMBTubus), and duration 5% (dur
      5) were calculated. Arterial blood pressure and heart rate were recorded before
      anaesthesia, after induction of anaesthesia, 2-times after mivacurium
      application, and after intubation. All data were compared using Kruskal-Wallis
      test corrected for multiple comparisons, Friedman test, or chi 2-test (*: p <
      0.05). Logarithms of dur 5 and PChEd were correlated using linear regression.
      RESULTS: Demographic data were comparable between all groups. PChEd was 3.7
      (3.0/4.1) kU/l in group C, 3.2 (2.2/4.8) kU/l in group P, and 3.5 (2.5/4.0) kU/l
      in group T, respectively. There were no differences between groups, neither in
      the NMBmax, in NMBTubus, or in onset times. But dur 5 was significantly longer in
      patients with renal impairment, both preterminal and also end-stage (medians: 11
      min in group K, 16 min in group P, 17 min in group T). Emphasis, however, is put
      on the broad range between 5 and 47 min of dur 5 in group P, and between 6 and 53
      min in patients of group T which is clinically more important than the
      differences in the median values. Dur 5 correlates with PChEd (p = 0.0001).
      Intubation conditions were excellent (relaxed vocal cords, easy passage of the
      tube, without coughing) in approximately 70% of all 59 patients without
      significant differences between groups. In 8 patients conditions were poor
      (successful intubation, inspite of moderately adducted vocal cords, but moderate
      coughing after passage of the endotracheal tube). There were no clinically
      relevant hemodynamic changes in each group in the time between injection of 0.15
      mg/kg mivacurium slowly and intubation 2.5 min later. DISCUSSION: Our findings
      suggest that 0.15 mg/kg mivacurium is an effective and safe intubation dose in
      healthy patients as well as in patients with renal impairment, inspite of a
      prolonged duration in patients with renal impairment. Low PChE in some, but not
      in all patients with a renal dysfunction indicates involvement of impaired
      hepatic function. There was a close correlation between the PChEd and dur 5.
      Therefore mivacurium dosage should be reduced in patients with compromised renal
      function, mainly if there are additional systemic, especially hepatic diseases.
      Thus, in patients with impaired renal function, relaxometry may be of high valu

PMID- 8868529
TI  - [Intranasal administration of midazolam (Dormicum) in young children in emergency
      medicine].
AB  - A method for sedation of preschool children in emergency medicine is presented.
      Midazolam (Dormicum) is frequently used in premedication in children. Various
      routes of administration have been described for this drug. After use of nasal
      administration of midazolam for premedication we also used this method for
      sedation of children in emergencies. This technique provides rapid onset and
      cardiovascular stability while maintaining spontaneous ventilation. In two case
      reports the first results are demonstrated; the method is evaluated and
      discussed.

PMID- 8868530
TI  - [Continuous fiberoptic monitoring of oxygen saturation in cerebral veins in
      severe craniocerebral trauma--experiences and results].
AB  - AIM: Monitoring of jugular-venous O2-saturation (SjO2) enables the assessment of
      cerebral oxygen supply and the rapid detection of cerebral desaturation in
      patients with severe head injury. Furthermore, it may help to optimize
      circulation, ventilation, and intracranial hypertension therapy in these
      patients. This study was performed to evaluate the reliability of SjO2-monitoring
      as well as to measure cerebral O2-extraction and the frequency of episodes of
      cerebral desaturation after traumatic brain injury. METHODS: In 16 patients with
      severe head injury (GCS 3-8), SjO2 (fibreoptic system), arterial blood pressure,
      and intracranial pressure were continuously recorded after admission of the
      patients to the intensive care unit. Fluctuations of SjO2 (> 10% within 30 min),
      which were not included by therapeutic measures, were classified by off-line
      analysis as irregular-isolated or irregular-combined, if accompanied by similar
      fluctuations of ICP and arterial blood pressure. Recordings which were unreliable
      due to technical reasons, mainly because of wall adherence of the tip of the
      fibreoptic catheter, were evaluated separately. Episodes of cerebral
      desaturations (SjO2 < 50%) were assessed with regard to their frequency, duration
      (5-10/> 10 min) and underlying mechanisms. Cerebral O2-extraction was calculated
      as the difference between arterial and cerebrovenous O2-saturation and averaged
      for each day after trauma. RESULTS: Mean time of measurement for each patient was
      194 hrs, a total of 3106 hrs were recorded. The correlation coefficient between
      in-vivo and in-vitro measured SjO2 was r = 0.62 (n = 367, p < 0.001). Reliable
      and artifact-free measurements of SjO2 were obtained only during 58.3% of all
      hours. Irregular-isolated fluctuations of the SjO2 occurred in 22.2% of the
      hours, and technical problems in 14.5%. Erroneous readings due to irregular
      combined fluctuations of the jugular-venous O2-saturation were detected in 5.0%
      of the time periods. A total number of 66 episodes of cerebral desaturation (SjO2
      < 50%) were found in all 16 patients, 41 of them had a duration of more than 10
      minutes. Cerebral hypoxia was attributed to low cerebral perfusion pressure in
      35% and hypocapnia in 17%. Global cerebral O2-extraction was significantly
      elevated at the day of injury compared to days 1-5 after trauma (37.4% vs. 28.9%
      31.9%, p < 0.05). CONCLUSIONS: Monitoring of SjO2 in severe head injury provides
      an estimate of cerebral oxygen supply and may improve the assessment of
      therapeutic measures in these patients. The high incidence of erroneous readings
      of the SjO2 is a major drawback of this method. Initially after trauma, a high
      extraction of oxygen was found, followed by a marked decrease in the subsequent
      days, presumably reflecting an early, decreased cerebral blood flow and a
      hyperaemic flow pattern thereafter. Continuous measurements of SjO2 may
      contribute to advanced, organ-specific cerebral monitoring in severe
      craniocerebral trauma. The reliability of data, however, should be considerably
      improved for common clinical use.

PMID- 8868528
TI  - [The effect of midazolam after intranasal administration on spontaneous
      respiration and respiratory control in young children].
AB  - AIM: The aim of this study was to investigate the influence of intranasally
      administered midazolam in different doses on spontaneous respiration in children.
      METHODS: 40 children received in randomised order 0.2, 0.4 or 0.6 mg/kg b.w.
      midazolam intranasally or NaCl 0.9% as control. 10 minutes later, anaesthesia was
      induced by inhalation of halothane, nitrous oxide and oxygen. The children were
      breathing spontaneously at a PEEP of 5 cm H2O on a circle system with a fresh gas
      flow of 61/min (FIO2 = 0.33). Intubation was performed in deep anaesthesia
      without muscle relaxant. Halothane concentration was reduced to an endtidal
      concentration of 0.4 Vol%. With a baby pneumotachograph, minute ventilation,
      tidal volume, peak inspiratory and expiratory flow and respiratory rate were
      recorded during quiet breathing. Endtidal pCO2 was measured. Ventilation was then
      stimulated with 0.2 and 0.41/min CO2 and the same parameters were recorded.
      Regression analysis was performed for minute ventilation and endtidal pCO2 to
      obtain the slope which is a parameter for the sensitivity of the chemoreceptor
      mediated control of ventilation. RESULTS: The tidal volume and peak inspiratory
      flow were significantly reduced for a dose of 0.6 mg/kg compared to the control
      group. No statistical difference could be found for any other parameter between
      the control and study groups. CONCLUSION: We conclude that nasally administered
      midazolam reduces tidal volume and inspiratory peak flow in spontaneously
      breathing children at a dose of 0.6 mg/kg b.w. compared to control during
      halothane--nitrous oxide--oxygen anaesthesia. The CO2 mediated control of
      respiration under this condition is preserved.

PMID- 8868531
TI  - [Diagnosis of magnesium deficiency in intensive care patients].
AB  - AIM: Magnesium deficiency was investigated in critically ill patients, comparing
      measurements of plasma concentrations with the results obtained by the magnesium
      tolerance test. DESIGN AND METHODS: 20 critically ill patients (5 females, 15
      males) between the ages of 27 and 86 were investigated. Magnesium plasma
      concentrations were determined before the magnesium tolerance test according to
      Ryzen was performed. For this purpose, magnesium sulfate (0.1 mmol/kg) was
      infused intravenously over four hours. Renal magnesium excretion was measured in
      the 24 h urine beginning at the start of the infusion. Magnesium concentrations
      in plasma and urine were determined using atomic absorption spectrophotometry.
      MAIN RESULTS: In 12 patients magnesium plasma concentrations were decreased to
      0.58-0.79 mmol/l. 6 patients showed values within the normal range of 0.80 to 1.0
      mmol/l. In 2 patients the plasma concentration was increased to 1.07 and 1.27
      mmol/l. Parenteral magnesium tolerance testing revealed a considerable magnesium
      deficiency by retention of 65-100% of the loading dose in 14 of the 20 patients.
      The remaining 6 patients retained 23-48% of the loading dose, thus demonstrating
      a moderate magnesium deficiency. CONCLUSION: Determination of magnesium plasma
      concentration appears suitable as an informative preliminary survey, since low
      values are reliable indicating a magnesium deficiency. However, this study
      confirms that normal magnesium plasma concentrations do not exclude a
      considerable magnesium deficiency, which is more sensitively determined by the
      magnesium tolerance test.

PMID- 8868532
TI  - [Economic control in anesthesia and intensive care medicine--do we need new
      muscle relaxants? Contra].

PMID- 8868533
TI  - [Economic control in anesthesia and intensive care medicine--do we need new
      muscle relaxants? Pro].

PMID- 8868534
TI  - [Jonnesco total spinal anesthesia].

PMID- 8868535
TI  - [Perioperative management of the patient with atypical Parkinson disease].
AB  - Recent neuropathological findings define that 10-20% of the Parkinson patients
      belong to the atypical Parkinson's syndrome due to multi-system disease marked by
      typical Parkinsonian symptoms such as rigor, tremor and akinesia and early onset
      of severe autonomic, cerebellar or pyramidal disorders. Symptoms like postural
      hypotension, dysphagia, hypersalivation, urinary bladder dysfunction,
      thermodysregulation, abnormalities in eye movement, early falls or dementia etc.
      are frequently seen in these patients. In these patients dopamin depletion in the
      nigrostriatal pathway is combined with degeneration of other cerebral structures
      like olivopontocerebellar and intermediolateral columns. Patients need high
      dosages of L-dopa and other antiparkinsonian drugs with poor prognosis in
      general. First, we report on an atypical Parkinson patient who developed acute
      dyspnoea and muscle rigidity after general anaesthesia; second, on another
      patient who took a long time to recover from general anaesthesia. Both responded
      to antiparkinsonian drugs, the first to orally applied L-dopa, the second to
      intravenous amantadine. Most probably the interruption of the treatment with high
      dosages of L-dopa (in these patients given in 2-4 hours intervals) had caused
      these complications. The special nature of the anaesthesiological management of
      atypical Parkinson patients is reviewed.

PMID- 8868536
TI  - [Arthrogryposis multiplex congenita: special anesthesiological aspects].
AB  - Case report on a 2.5-year old girl suffering from arthrogryposis multiplex
      congenita (AMC) who was admitted for an extensive orthopaedic operation of
      equinovarus. The patient showed typical AMC-related problems such as skin and
      subcutaneous tissue abnormalities, lack of veins, contractural deformities of all
      four limbs and microgenia. Problems associated with anaesthesia in this patient
      were difficult intubation and venipuncture and a potential risk of developing
      malignant hyperthermia when using volatile anaesthetics. For preoperative blood
      chemistry sampling and intravenous induction of general anaesthesia, the patient
      received a central venous catheter under local and N2O/O2 anaesthesia on the day
      before surgery. Following intravenous induction of trigger-free anaesthesia using
      fentanyl, thiopental and vecuronium, the child was intubated and ventilated with
      30% O2 in N2O the next day. A caudal catheter was inserted for intraoperative
      reduction of anaesthetics and postoperative pain relief. Intraoperatively, caudal
      anaesthesia was performed with 2 ml of 2% mepivacaine every 90 min. No
      inadvertent reactions were seen during a 7 h operation. In the recovery room, the
      patient received 4 ml of plain 0.25% bupivacaine per 4 h via the caudal catheter
      and had excellent analgesia during 24 postoperative hours. The following course
      was uneventful and the child was discharged from hospital two weeks later. AMC
      related problems concerning the management of anaesthesia are discussed.

PMID- 8868537
TI  - Smoking and women: a major "disconnect".

PMID- 8868538
TI  - Smoking v women's health: the challenge ahead.

PMID- 8868539
TI  - Response to medicine and abortion issue.

PMID- 8868540
TI  - Response to medicine and abortion issue.

PMID- 8868541
TI  - Trends and effects of cigarette smoking among girls and women in the United
      States, 1965-1993.
AB  - Each year, cigarette smoking causes more than 140,000 deaths among women in the
      United States. Here, we describe smoking trends among girls and women, including
      women of reproductive age and pregnant women. We also provide data regarding the
      prevalence of indicators of nicotine dependence among women in the United States.
      The data were derived from the National Health Interview Survey, High School
      Seniors Survey, National Household Survey on Drug Abuse, and Teenage Attitudes
      and Practices Survey. The prevalence of smoking among women overall is now
      declining at a rate comparable to that of men, and women are attempting cessation
      and maintaining abstinence at the same rate as men. However, smoking prevalence
      among women in certain demographic groups such as American Indians and Alaska
      Natives is high. Although the prevalence of smoking increased among young women
      (particularly women of lower educational attainment) in the early 1980s, more
      recent surveys show it is declining. Smoking prevalence among young black and
      Hispanic women is decreasing, but progress in decreasing smoking prevalence among
      young white women is slow. Young women appear to be as nicotine dependent as
      older women, and light smokers of all ages report indicators of nicotine
      dependence.

PMID- 8868542
TI  - Nicotine dependence in women.
AB  - Cigarette smoking is the most preventable cause of death in the United States,
      accounting for the deaths of approximately 140,000 women annually. Despite the
      known health risks, women continue to begin and continue smoking at high rates.
      Like other addictive drugs, nicotine becomes reinforcing with repeated use,
      induces euphoric sensations, and is self-administered. Tolerance to nicotine's
      effects develops rapidly and leads to increased use. Reducing or suppressing
      tobacco consumption produces a withdrawal syndrome characterized by irritability,
      difficulty concentrating, cognitive impairments, and weight gain. These
      withdrawal symptoms, along with other factors, lead to relapse rates comparable
      to those following cessation from other addictive drugs. This review article
      discusses the pathogenesis of nicotine addiction compared to other addictive
      substances such as cocaine and heroin with an effort to provide comparative data
      for men and women.

PMID- 8868543
TI  - Nicotine: a gateway drug?

PMID- 8868544
TI  - Smoking among adolescent girls: prevalence and etiology.
AB  - The prevalence of regular cigarette smoking among 12th-grade girls is about 28%,
      with the highest rates among whites and the lowest in African-Americans and
      Asians. Adolescent girls who do not go on to college are more likely to smoke
      cigarettes than those with college plans. Girls initiate smoking for diverse
      reasons; it may be instrumental in attaining a desired self-image that includes
      feelings of maturity, independence, sexuality, health, and sociability. In
      addition, tobacco advertisements have exploited white, middle-class women's
      concerns with staying slim by emphasizing the weight-controlling benefits of
      smoking. Parents, peers, and friends are influential in creating norms that
      support or discourage smoking. Reasons for ethnic differences in smoking
      prevalence among adolescent females are poorly understood, but may be linked to
      economic and sociocultural factors. Future prevention and treatment programs
      targeting young women should address their reasons for smoking and identify
      healthful alternative behaviors that will serve psychosocial functions previously
      met by cigarette smoking.

PMID- 8868545
TI  - Smoking and reproductive health.

PMID- 8868546
TI  - Smoking cessation techniques.
AB  - A key responsibility for all health care professionals is to advise patients to
      quit smoking, which means being knowledgeable about smoking cessation programs
      and methods. This article considers both assisted and self-help methods of
      smoking cessation and their application to female smokers. The most effective
      assisted programs employ multiple interventions, primarily behavioral, but also
      pharmacologic, in the form of nicotine replacement. Smoking cessation products
      have not generally proven effective with the exception of nicotine polacrilex gum
      and the transdermal nicotine patch. Use of nicotine replacement, especially the
      patch, in smokers who are pregnant or nursing is controversial. In addition to
      pregnant women, those with young children and those of color and low
      socioeconomic status represent important high-risk target populations. Very
      little work has been done with female adolescents.

PMID- 8868548
TI  - How clinicians can affect patient smoking behavior through community involvement
      and clinical practice.

PMID- 8868547
TI  - Smoking cessation and gender: the influence of physiological, psychological, and
      behavioral factors.
AB  - While gender differences in smoking cessation do exist, it is unclear whether
      these differences affect smoking cessation outcomes. Large population-based
      surveys have shown few gender differences in the ability to quit or to stay quit;
      conflicting reports continue to emerge from individual studies, however. Existing
      evidence evaluating possible gender differences related to physiological,
      psychological, and behavioral factors is reviewed in this paper. Physiological
      factors affecting women include: differential sensitivity and tolerance to
      nicotine, greater withdrawal symptoms, and the importance of timing quit attempts
      in relation to the menstrual cycle. Behavioral and psychological factors include
      the following: fear of weight gain, need for social support, depression and
      negative affect smoking, self-efficacy (confidence in ability to quit), and stage
      of change (readiness to quit smoking). The majority of studies report gender
      pooled data and lack the power to identify differential trends. Gender should be
      used as a stratification variable in the design of smoking cessation studies
      whenever feasible. To justify gender-specific interventions, more prospective,
      randomized studies need to be undertaken.

PMID- 8868549
TI  - Women and tobacco: international issues.
AB  - Most women live in the developing world, and of these, between 2% and 10% smoke
      cigarettes, although in some regions women more commonly chew tobacco. There can
      be no complacency about the lower level of tobacco use among women; it does not
      reflect health awareness, but rather social traditions and women's low economic
      resources. The number of women smokers will inevitably increase: the female
      population in developing countries will rise from the present 2.1 to 3.5 billion
      by 2025, women's spending power is increasing, the tobacco companies are
      targeting women, governments may be less aware of the harmfulness of smoking and
      are preoccupied with other health issues, and woman-specific health education and
      quitting programs are rare. Tobacco-related health problems have hitherto been
      masked by women's shorter life expectancy, but rural women who become sick from
      tobacco-related diseases have extremely limited access to health care. In
      addition, tobacco inflicts a particularly heavy economic burden on women in
      developing countries. Women's health organizations in Western countries have a
      special responsibility in addressing, reducing, and preventing further expansion
      of the global tobacco epidemic among women.

PMID- 8868550
TI  - Public policy: effective treatment for tobacco disease.
AB  - Public policy initiatives offer greater promise than other strategies for
      reducing the major public health problem of death and disease due to smoking.
      Three of the most critical public policy areas today are smoke-free environments,
      youth access, and advertising. While earlier laws separated smokers and
      nonsmokers into separate sections, the focus now is on smoke-free environments.
      Various places, however, most notably restaurants, often remain polluted with
      tobacco smoke and put women at heightened risk of disease and death. Restricting
      youth access to tobacco products has also gained momentum in the 1990s. The
      recently proposed Food and Drug Administration regulations designed to reduce
      smoking by minors by 50% over seven years are the most significant national
      public policy initiatives ever to address the problem of children smoking.
      Measures to counter the tobacco industry's massive advertising and promotion
      campaigns have also increased. The federal government has begun enforcing the
      prohibition on cigarette advertising on television, and local jurisdictions have
      restricted tobacco billboards and point-of-sale advertising.

PMID- 8868551
TI  - Tobacco litigation as a public health and cancer control strategy.
AB  - OBJECTIVE: To provide an overview of the class action and medical cost
      reimbursement suits of the third wave of tobacco litigation and to analyze their
      chances for success and their efficacy as a public health and cancer control
      strategy. METHOD/DATA SOURCES: The application of standard, predictive legal
      reasoning to documents from three class action lawsuits, four of the five state
      medical cost reimbursement lawsuits, documents from the tobacco industry, and
      appropriate secondary sources. CONCLUSIONS: Victory in any of the class actions
      would result in a transfer of costs, albeit an inefficient one, from injured
      smokers to the tobacco industry. Victory in any of the medical cost reimbursement
      suits would result in a transfer of costs from injured states forced to shoulder
      the economic burden of tobacco-induced illnesses to the tobacco industry. Such a
      transfer of costs would likely have the immediate impact of significantly
      lowering cigarette consumption, while the long-term effects would probably be
      much more devastating. Victory in at least some of the third wave cases is
      likely, because a number of factors promise to enable plaintiffs to overcome the
      previously impenetrable defenses of the tobacco industry.

PMID- 8868552
TI  - Recruiting women smokers: the engineering of consent.
AB  - A range of social forces contributed to the effective recruitment of women to
      cigarette smoking in the crucial period between 1900 and 1940. Cigarette
      advertisers and public relations experts recognized the significance of women's
      changing roles and the rising culture of consumption, and worked to create
      specific meanings for the cigarette to make it appeal to women. The cigarette was
      a flexible symbol, with a remarkably elastic set of meanings; for women, it
      represented rebellious independence, glamour, seduction, and sexual allure, and
      served as a symbol for both feminists and flappers. The industry, with the help
      of advertisers and public relations experts, effectively engineered consent for
      women as smokers. The "engineering of consent" has a role to play in smoking
      cessation, since negative meanings for the cigarette can be engineered as well.

PMID- 8868553
TI  - Deadly targeting of women in promoting cigarettes.
AB  - The history of tobacco marketing portrays a strong relationship between cigarette
      advertising targeted to women and the rise in the prevalence of women smoking.
      This article describes how tobacco companies crafted their marketing strategies
      to obfuscate the growing evidence of the health hazards of tobacco and to
      circumvent attempts to regulate cigarette advertising. It shows how the tobacco
      industry understood and capitalized on the women's liberation movement to sell
      cigarettes as symbols of freedom and emancipation, tracing the creation and
      promotion of Virginia Slims as a case study. And it documents the unfortunate
      success of these marketing strategies as reflected in the trends of tobacco use,
      especially among underage girls, and the commensurate increase in tobacco-related
      disease and death among women.

PMID- 8868554
TI  - Physician strategies in a managed care environment.

PMID- 8868555
TI  - Lead poisoning: the implications of current biomedical knowledge for public
      policy.
AB  - New information on the nature and extent of lead poisoning, as well as on sources
      and toxicokinetics of lead, is relevant to the development of effective public
      health policy. Lead at low levels of exposure is now recognized to be toxic, and
      it is difficult to discern a threshold for lead toxicity in populations exposed
      to lead at levels nearly 200 times those experienced by pre-industrial humans.
      Although some sources of lead have been controlled, notably lead in gasoline,
      there are persistent lead sources associated with past uses of lead in paints,
      plumbing, and gasoline. In Baltimore City, nearly 50% of children screened in
      1993 had blood lead levels in excess of guidelines issued by the Centers for
      Disease Control and Prevention. Much of this exposure is associated with lead
      based paint in housing.

PMID- 8868556
TI  - Effects of movies on children's emotional health.
AB  - Parents are in a dilemma when it comes to deciding what films they should allow
      their children to see. They know intuitively that some viewing experiences are
      entertaining while others are potentially harmful. The authors have been viewing
      films and talking with parents, educators, and mental health professionals for
      several years to try to answer questions posed by these conscientious but
      frustrated parents. This article, the first published regarding our findings,
      describes the history of today's movie rating system, which represents an early
      but inadequate attempt to offer parents guidance. A recent film, The Lion King,
      will demonstrate a developmental approach to thinking about movies for children.
      This method uses current research on the effects of movies on children and
      knowledge of child development to predict reactions of children in particular age
      groups to elements in a movie.

PMID- 8868557
TI  - Identification of childhood vaccine providers in Maryland.
AB  - The purpose of the study was to compare the utility of an American Medical
      Association (AMA)-derived list and a Maryland State Department of Health and
      Mental Hygiene (state)-derived list of potential childhood vaccine providers
      (CVPs) in identifying true childhood vaccine providers for the Vaccines for
      Children (VFC) program in Maryland. A telephone survey of a sample of physicians
      from the two lists was used to determine their status as providers of routine
      vaccinations to children. Results showed a significant difference between the two
      lists. The state-derived list was composed of an estimated 60.7% CVPs, whereas
      the AMA-derived list was composed of an estimated 36.7% CVPs. Using the capture
      recapture method, it was estimated that there are about 2077 CVPs in Maryland.
      Based on this figure, the state-derived list would have identified 71.7% of the
      state's CVPs, and the AMA-derived list would have identified 59.4%. Using the AMA
      derived list would have required contacting approximately 1800 extra providers to
      identify the additional 350 CVPs (16.8%) not identified in the state-derived
      list. Accurate, up-to-date lists of providers that include pertinent practice
      characteristics would enhance the ability to contact specific providers for VFC
      program enrollment and for other clinical and public health purposes.

PMID- 8868558
TI  - Chronic pain control in the elderly.

PMID- 8868559
TI  - Benign thyroid nodules.

PMID- 8868560
TI  - Ethnobotany in Maryland: dittany.

PMID- 8868561
TI  - Cross-cultural considerations in health care delivery: Chinese viewpoints.

PMID- 8868562
TI  - John Fonerden, M.D., med chi's first librarian.

PMID- 8868563
TI  - John Ruhrah, M.D., a colleague to emulate.

PMID- 8868565
TI  - Parameter extraction from population codes: a critical assessment.
AB  - In perceptual systems, a stimulus parameter can be extracted by determining the
      center-of-gravity of the response profile of a population of neural sensors.
      Likewise at the motor end of a neural system, center-of-gravity decoding, also
      known as vector decoding, generates a movement direction from the neural
      activation profile. We evaluate these schemes from a statistical perspective, by
      comparing their statistical variance with the minimum variance possible for an
      unbiased parameter extraction from the noisy neuronal ensemble activation
      profile. Center-of-gravity decoding can be statistically optimal. This is the
      case for regular arrays of sensors with gaussian tuning profiles that have an
      output described by Poisson statistics, and for arrays of sensors with a
      sinusoidal tuning profile for the (angular) parameter estimated. However, there
      are also many cases in which center-of-gravity decoding is highly inefficient.
      This includes the important case where sensor positions are very irregular.
      Finally, we study the robustness of center-of-gravity decoding against response
      nonlinearities at different stages of an information processing hierarchy. We
      conclude that, in neural systems, instead of representing a parameter explicitly,
      it is safer to leave the parameter coded implicitly in a neuronal ensemble
      activation profile.

PMID- 8868564
TI  - Optimizing synaptic conductance calculation for network simulations.
AB  - High computational requirements in realistic neuronal network simulations have
      led to attempts to realize implementation efficiencies while maintaining as much
      realism as possible. Since the number of synapses in a network will generally far
      exceed the number of neurons, simulation of synaptic activation may be a large
      proportion of total processing time. We present a consolidating algorithm based
      on a recent biophysically-inspired simplified Markov model of the synapse. Use of
      a single lumped state variable to represent a large number of converging synaptic
      inputs results in substantial speed-ups.

PMID- 8868566
TI  - Energy efficient neural codes.
AB  - In 1969 Barlow introduced the phrase "economy of impulses" to express the
      tendency for successive neural systems to use lower and lower levels of cell
      firings to produce equivalent encodings. From this viewpoint, the ultimate
      economy of impulses is a neural code of minimal redundancy. The hypothesis
      motivating our research is that energy expenditures, e.g., the metabolic cost of
      recovering from an action potential relative to the cost of inactivity, should
      also be factored into the economy of impulses. In fact, coding schemes with the
      largest representational capacity are not, in general, optimal when energy
      expenditures are taken into account. We show that for both binary and analog
      neurons, increased energy expenditure per neuron implies a decrease in average
      firing rate if energy efficient information transmission is to be maintained.

PMID- 8868567
TI  - A nonlinear Hebbian network that learns to detect disparity in random-dot
      stereograms.
AB  - An intrinsic limitation of linear, Hebbian networks is that they are capable of
      learning only from the linear pairwise correlations within an input stream. To
      explore what higher forms of structure could be learned with a nonlinear Hebbian
      network, we constructed a model network containing a simple form of nonlinearity
      and we applied it to the problem of learning to detect the disparities present in
      random-dot stereograms. The network consists of three layers, with nonlinear
      sigmoidal activation functions in the second-layer units. The nonlinearities
      allow the second layer to transform the pixel-based representation in the input
      layer into a new representation based on coupled pairs of left-right inputs. The
      third layer of the network then clusters patterns occurring on the second-layer
      outputs according to their disparity via a standard competitive learning rule.
      Analysis of the network dynamics shows that the second-layer units'
      nonlinearities interact with the Hebbian learning rule to expand the region over
      which pairs of left-right inputs are stable. The learning rule is
      neurobiologically inspired and plausible, and the model may shed light on how the
      nervous system learns to use coincidence detection in general.

PMID- 8868569
TI  - Predictive minimum description length criterion for time series modeling with
      neural networks.
AB  - Nonlinear time series modeling with a multilayer perceptron network is presented.
      An important aspect of this modeling is the model selection, i.e., the problem of
      determining the size as well as the complexity of the model. To overcome this
      problem we apply the predictive minimum description length (PMDL) principle as a
      minimization criterion. In the neural network scheme it means minimizing the
      number of input and hidden units. Three time series modeling experiments are used
      to examine the usefulness of the PMDL model selection scheme. A comparison with
      the widely used cross-validation technique is also presented. In our experiments
      the PMDL scheme and the cross-validation scheme yield similar results in terms of
      model complexity. However, the PMDL method was found to be two times faster to
      compute. This is significant improvement since model selection in general is very
      time consuming.

PMID- 8868568
TI  - Coupling the neural and physical dynamics in rhythmic movements.
AB  - A pair of coupled oscillators simulating a central pattern generator (CPG)
      interacting with a pendular limb were numerically integrated. The CPG was
      represented as a van der Pol oscillator and the pendular limb was modeled as a
      linearized, hybrid spring-pendulum system. The CPG oscillator drove the pendular
      limb while the pendular limb modulated the frequency of the CPG. Three results
      were observed. First, sensory feedback influenced the oscillation frequency of
      the coupled system. The oscillation frequency was lower in the absence of sensory
      feedback. Moreover, if the muscle gain was decreased, thereby decreasing the
      oscillation amplitude of the pendular limb and indirectly lowering the effect of
      sensory feedback, the oscillation frequency decreased monotonically. This is
      consistent with experimental data (Williamson and Roberts 1986). Second, the CPG
      output usually led the angular displacement of the pendular limb by a phase of 90
      degrees regardless of the length of the limb. Third, the frequency of the coupled
      system tuned itself to the resonant frequency of the pendular limb. Also, the
      frequency of the coupled system was highly resistant to changes in the endogenous
      frequency of the CPG. The results of these simulations support the view that
      motor behavior emerges from the interaction of the neural dynamics of the nervous
      system and the physical dynamics of the periphery.

PMID- 8868570
TI  - Structural identifiability of models characterizing saturable binding: comparison
      of pseudo-steady-state and non-pseudo-steady-state model formulations.
AB  - A two-state variable model in which saturable binding takes place is studied. Two
      mathematical representations of the same model are considered, one a standard
      chemical kinetics type of polynomial system, the other a reduced model formed
      from the original system via a pseudo-steady-state approximation. For a
      particular experiment the structural identifiability of the set of unknown
      parameters of each model is examined using the similarity transformation
      approach. The analysis shows that when the pseudo-steady-state approximation is
      made a certain degree of structural identifiability is lost in the sense that
      fewer individual parameters can be uniquely identified.

PMID- 8868571
TI  - Creating phyllotaxis: the stack-and-drag model.
AB  - The genesis of phyllotaxis, the origin of the pattern of appendages on the
      surface just below the apical extreme of many plants, is an old unsolved puzzle.
      Whereas many models generate helices, the stack-and-drag model is the first to
      achieve this in an integral construction from seed to flower. Combination of the
      principle of gnomonic growth, where consecutive additions have comparable
      positions, with a "dragging" principle, where the developing zone follows the
      apical tip, provides a powerful tool in simulating a wide range of phyllotactic
      manifestations. The influence of three vital parameters for primordial size,
      compressibility, and canalization (or annular arrangement) helps in understanding
      the problem's nature.

PMID- 8868572
TI  - Nonparametric density estimation applied to population pharmacokinetics.
AB  - Kinetic parameters are estimated to assess absorption, distribution, metabolism,
      and elimination of a drug in a subject. In a group of subjects, pharmacokinetic
      population studies are developed to describe the variability and to detect
      particular subsets by establishing the relationships between kinetic parameters
      and easily measurable subject characteristics, the covariates (age, body weight,
      etc.). The usually proposed methods are based on linear regression equations
      relating kinetic parameters to the covariates. We propose to measure these
      dependencies and describe the interindividual variability through the joint
      probability density function. This function is estimated by a nonparametric
      method superposing potential functions or kernels over the sample. In this
      estimation, the Shannon information theory was applied to determine the number of
      individuals needed to describe the variability reliably and to screen informative
      covariates with respect to the kinetic parameters. This approach was used to
      obtain the nonparametric conditional probability density functions of the kinetic
      parameters, given the covariates. These functions supplied prior information for
      a Bayesian estimation. The feasibility of the global approach was illustrated by
      a simulation in which nonlinear relations link covariates and pharmacokinetic
      parameters. The performance of this new estimator using covariates was compared
      with that of the usual Bayesian estimation.

PMID- 8868573
TI  - Competition and the canonical ensemble.
AB  - Gibbs' canonical ensemble model from equilibrium statistical mechanics furnishes
      solutions to Eigen's phenomenological rate equations under constant total
      organization in cases with or without mutability. The evolution of species with
      mutation under constant total organization reduces to the evolution of
      substantial virtual species without mutation under the same constant total
      organization. Application of the canonical ensemble model provides an exact
      correspondence between thermodynamic and biological parameters. In particular,
      evolutionary time, as the analog of temperature, emerges as a statistical
      aggregate of the condition of the evolving system.

PMID- 8868574
TI  - Modeling nucleotide evolution: a heterogeneous rate analysis.
AB  - A new model of molecular evolution is introduced that allows for heterogeneous
      rates across the sequence positions. The development of this model was motivated
      by two issues: first, a number of studies have shown that the positions in a DNA
      sequence evolve at different rates, and second, it has been shown that not
      accounting for this heterogeneity can lead to biased estimates of evolutionary
      parameters. The authors generalize the Markovian model of molecular evolution to
      allow for heterogeneous rates and explore some of the consequences of such a
      model. In particular, they quantify the biases incurred by incorrectly assuming
      an equal-rate model and consider what can be learned about evolutionary
      parameters under a heterogeneous model.

PMID- 8868575
TI  - Protection against alloxan diabetes by low-dose 60Co gamma irradiation before
      alloxan administration.
AB  - We evaluated the protective effects of a single low-dose whole body 60Co gamma
      irradiation against alloxan-induced hyperglycemia in rats. i) In rats that did
      not receive alloxan, the superoxide dismutase (SOD) activity in the pancreas
      significantly increased after irradiation at a dose of 0.5 or 1.0 Gy. ii) In rats
      that received alloxan, plasma lipid peroxide levels, pancreatic lipid peroxide
      levels and blood glucose were increased. However, the increase in pancreatic
      lipid peroxide level was prevented by irradiation at a dose of 0.5 or 1.0 Gy; and
      the increase in blood glucose, by irradiation at 0.5 Gy. iii) After alloxan
      administration, degranulation was observed in beta cells, but this was prevented
      by low-dose irradiation at 0.5 Gy.

PMID- 8868576
TI  - Effects of low-dose gamma-irradiation to the chest regions on the blood pressure
      of spontaneous hypertensive rats.
AB  - We examined changes in the blood pressure and the superoxide dismutase (SOD)
      activities in aortic tissue after gamma-irradiation to the chest regions of
      spontaneous hypertensive rats (SHR) and Wistar Kyoto rats (WKY), and obtained the
      following results. After 5 Gy irradiation, there was no change with time in the
      blood pressure in WKY rats, while a transient decrease (3 days later) was
      observed in SHR rats. The Cu/Zn-SOD activity in the aorta of SHR was less than
      that of WKY. 5 Gy irradiation induced an increase in the Cu/Zn-SOD activity in
      SHR nearly to the level observed in WKY, which remained unchanged upon
      irradiation. Therefore, unlike high-dose irradiation, irradiation at a relatively
      low-dose of 5 Gy to SHR appears to increase the aortic Cu/Zn-SOD activity, which
      is lacking in SHR, leading to a decrease in the blood pressure.

PMID- 8868577
TI  - Persisting in vitro actin motility at nanomolar adenosine triphosphate levels:
      comparison of skeletal and cardiac myosins.
AB  - We have previously demonstrated in vitro actin movement at nanomolar adenosine
      triphosphate (ATP) levels using heavy meromyosin from skeletal muscle. In the
      present work we tested whether the motility at nonomolar ATP-concentrations could
      be supported by cardiac myosin as well. Actomyosin (skeletal actin and bovine
      ventricular myosin) was pretreated in the in vitro motility assay with 1 mM ATP;
      subsequently, the ATP level was reduced by multiple rigor-solution washes. By the
      final rigor-solution wash, the ATP concentration, monitored by the luciferin
      luciferase assay, dropped to the order of 100 nM. Even at this low ATP level
      actin-filament movement remained in evidence. This was in marked contrast to the
      situation where ATP concentration was gradually increased from zero; in the
      latter, filament movement began only as ATP levels exceeded 1-2 microM. The
      difference indicates that potential energy is stored during the initial ATP
      treatment, and utilized later as the free ATP falls below micromolar levels.
      Although the velocity of cardiac myosin-supported movement was only one fourth of
      that of skeletal myosin, both myosins supported actin movement down to similar
      ATP concentrations. The similarity in response of the two myosins to ATP implies
      a similar degree of potential energy storage. Given the significantly different
      specific ATPase activities, however, it appears that the mechanism of potential
      energy storage and release involves factors different from those involved in the
      release of chemical energy by the myosin ATPase.

PMID- 8868578
TI  - Thermo- and photoelectric current in hornet cuticle.
AB  - Thermoelectric and photoelectric currents were measured in the cuticle of
      hornets. The spontaneous current in the studied specimens ranged between 30-40
      nAmp under conditions of darkness whereas under illumination the current drops to
      near zero. Upon warming up to 28-29 degrees C, the current rises to 50-200 nAmp
      but subsequently, after a while, it declines, regardless of whether the
      temperature is held steady, continues to rise or is lowered. In light, the
      current values are lower than in darkness and this under all conditions. When the
      specimen is charged with an electric current under fixed temperature, the current
      attains several microAmp in darkness but is usually less than that under
      illumination by about one order of magnitude. The capacitance values range
      between 1-7 mFarad both in light and in the dark. Possible mechanisms for
      creating this cuticular current and the changes which it undergoes under the
      various experimental conditions are discussed, and so also the properties of
      hornet cuticle as a semiconductor and possible applications of the described
      phenomena in everyday life of hornets.

PMID- 8868579
TI  - Light curtails sleep in anesthetized hornets: extraretinal light perception.
AB  - In the present study effects of light on the sleep duration of anesthetized
      hornets (Vespa orientalis) were investigated. Following initial anesthesia by
      diethyl ether the sleeping time of workers and drones at 22 degrees C in the dark
      was 59 +/- 15 min. After repeated anesthesia the sleeping time was 30 +/- 15 min
      in the dark. When exposed to polychromatic light from a halogen lamp of 230
      mW/cm2, focused on a spot of the cuticle of the hornet, the sleeping time was
      markedly shortened so that following initial as well as repeated anesthesia the
      hornets woke up after 4.5 +/- 2.9 min. Any decrease in light intensity resulted
      in an increase in the sleeping time but irradiances of less than 14 mW/cm2 had no
      measurable influence on the wake-up time. After illumination with polychromatic
      light from a mercury lamp the sleeping times were much shorter than after
      illumination with a halogen lamp at the same conditions and intensity. This
      difference is attributed to the relatively higher portion of U.V. light in the
      total emission of the Hg lamp. Effects of the spectral composition of the
      incident light beam on the wake-up of the sleeping hornets were also
      investigated. Near U.V. light in the 300-400 nm region was found to be most
      efficient. Shorter wavelengths as well as wavelengths between 400-470 nm had less
      influence and wavelengths above 470 nm had very little effect on the wake up. The
      sleeping times of hibernating queens were relatively longer than those of workers
      and drones under the same conditions. These effects are ascribed to the
      extraretinal light perception. The possible reasons underlying this phenomenon
      are discussed.

PMID- 8868580
TI  - Identification of perhydro-1,4-thiazepine-3,5-dicarboxylic acid, cystathionine
      mono-oxo acids, cystathionine ketimines, cystathionine sulfoxide and N
      acetylcystathionine sulfoxide in the urine sample of D,L-propargylglycine treated
      rats.
AB  - Novel cystathionine metabolites, perhydro-1,4-thiazepine-3,5-dicarboxylic acid
      (PHTZDC), cystathionine mono-oxo acids [S-(3-oxo-3-carboxy-n-propyl)cysteine and
      S-(2-oxo-2-carboxyethyl)homocysteine], cystathionine ketimines, cystathionine
      sulfoxide and N-acetylcystathionine sulfoxide were identified previously in the
      urine of patients with cystathioninuria. We have identified these compounds for
      the first time in the urine of D,L-propargylglycine-treated rats using LC/APCl-MS
      (liquid chromatography-mass spectrometry with an atmospheric pressure chemical
      ionization interface system) and an amino acid analyzer. Cystathionine mono-oxo
      acids and cystathionine ketimines were easily interconvertible depending on the
      pH of the solution. The excretion of PHTZDC, total cystathionine ketimine
      (cystathionine mono-oxo acids plus cystathionine ketimines), cystathionine
      sulfoxide and Nac-cystathionine sulfoxide in the rat urine increased in
      proportion to that of cystathionine content after D,L-propargylglycine
      administration.

PMID- 8868581
TI  - The periodic continuous effect: how the low energy irradiated matter behaves for
      successive irradiations.
AB  - This paper is related to periodic continuous responses of a new state derived
      from the interaction between low energies and matter. This effect was predicted
      by categoric developments and then verified by a photographic methodology. This
      experimental way is again used and once more it reveals new evidences on the
      structure of the irradiated matter and, consequently, on the mathematical
      properties of a Cartesian product operation used for the representations.
      Experiments with successive irradiations with visible light (lambda = 546.1 nm; I
      = 3350 lux) on a photographic developer (methyl-p-aminephenol sulfate) are
      reported.

PMID- 8868583
TI  - [Localization of the apical foramen using the newest electronic instruments:
      stereomicroscopy and SEM (scanning electron microscopy)].
AB  - Introduction of double impedence as new parameter in root canal length electronic
      measurement allowed first and second generation electronic apical localizers main
      problems overcoming: precision failure in presence of conducting fluids. Our
      study's purpose was an in vitro evaluation of two third generation instruments
      (Apit-Osada and Root ZX-Morita Corp.) ability in apical foramen localization
      using sodium hypoclorite as irrigating solution. 40 human monorooted teeth with
      immature apex were studied. 20 samples were measured by Apit and 20 by Root ZX;
      measurements were recorded when apical foramen was reached. Samples were fixed
      for stereomicroscope observation before and after apical 3 mm worn and prepared
      for SEM observation. Evaluations about each system's precision were made by
      calculating difference between foramen position determined by electronic
      localizer and its real anatomical position determined by a computed image
      analizing system linked to SEM. All measurements were included between a minimum
      value of -0.45 mm and a maximum value of 0.26 mm. Mann Whithney U test was
      performed to compare average values of the two sample groups but his was not
      meaningful (p = 0.18) showing that there is no valuable difference in accuracy
      between Apit and Root ZX. According to most researchers, who consider a +/- 0.5
      mm error range clinically acceptable, and considering that in vitro measurements
      never exceded this limit value we conclude confirming both instruments' safety.

PMID- 8868582
TI  - Antioxidant properties of the decarboxylated dimer of aminoethylcysteine
      ketimine.
AB  - The decarboxylated dimer of aminoethylcysteine ketimine has been investigated for
      a possible general protective effect against oxyradical damage. It has been found
      that the dimer protects brain microsomes against lipid peroxidation induced by
      NADPH in the presence of Fe(III)-ADP chelate or by cumene hydroperoxide. The
      compound also inhibits lipid peroxidation stimulated by L-dopa and related
      compounds in the presence of Fe(III)-ADP complex. Furthermore the dimer is able
      to protect deoxyribose against hydroxyl radical induced degradation. These
      observations suggest that the dimer is a lipid peroxidation protective agent and
      a free radical scavenger.

PMID- 8868584
TI  - [Bicoronal approach in the management of frontal sinus fractures].
AB  - The frontal sinus is located at the level of the junction between the naso
      ethmoido-orbital region, the cranial vault and the skull base and plays a
      particularly important role in the biomechanics of the centro-facial region. It
      represents a locus minoris resistentiae placed between the fronto-orbital frame,
      whose resistance to trauma is good, and the thin posterior fronto-ethmoidal
      structures. Fractures of the frontal sinus more frequently involve the anterior
      wall of the frontal sinus and, occasionally, also the posterior wall and the base
      of the sinus. Where the fracture involves the anterior sinsu wall alone, surgical
      reduction is indicated to correct cosmetic defects arising from an altered bone
      profile, either via bicoronal access or by direct attack when there are skin
      lesions too. If the fracture extends to the posterior wall of the sinus without
      causing bone displacement or dural lesion, most authors agree that only the
      fractures of the anterior wall should be treated to avoid obliterating the sinus
      cavity. When the fracture of the posterior wall is comminuted with displacement
      of bone fragments, there are usually dural lesions too; in this event, once dural
      plasty has been performed, it is necessary to cranialize the frontal sinus by
      demolishing its posterior wall. Fractures of the skull base, associated with a
      high frequency of lesion or obstruction of the sinusal ostio and severe infective
      complication, require cranialization of the sinus that is also separated from the
      cranial cavity using a median-pedicled pericranial flap. To control the point of
      fracture, a rigid fixation system can be employed (microplates) or osteosynthesis
      with metal wires that restore the eurhythm of the frontal-orbital region and
      simultaneously guarantee good stability of the repositioned fragments.

PMID- 8868585
TI  - [Fine needle biopsy in the preoperative diagnosis of parotid tumors].
AB  - Fine-needle aspiration biopsy is of particular interest in the parotid sites
      because, here, pathology with different treatments and prognosis manifest
      themself in the same way. The preoperative diagnosis of neoplasm is often
      problematic. As is known, this is correlated to several factors including
      histology, clinical and instrumental semiology. The instrumental image techniques
      (sialography, thermography, scintigraphy, ultrasound diagnosis, tac sialo-tac)
      give information as to size and location of the mass in question. Only rarely
      does it give any indication of whether the mass is malignant or benign. The
      authors systematically studied 386 parotid tumors. The method utilises a
      traditional technique (needle n. 12/2 gauge 1/4) and microscope examination with
      immediate dyeing to verify the correctness of the sample. 352 cases underwent
      surgery with subsequent histological verification. The results demonstrated a
      generical concordance of cytology and histology in the diagnosis of malignancy
      equal to 95%. The concordance of exact histology was 91%. The discordance
      regards, above all, the malignant neoplasm and particularly the mucoepidermoide
      and the adenoid cystic carcinoma. Fine needle aspiration demonstrates absolute
      specificity in the differential diagnosis between parotid and extraparotid
      pathology.

PMID- 8868586
TI  - [Metastatic tumors of the mandible. Review of the literature].
AB  - Every cancer can produce bone metastases. Metastatic tumors to the maxillo-facial
      bones are rare, mandible is the most frequent place of these bones. Often
      metastases represent the first symptom of malignant tumors.

PMID- 8868587
TI  - [Endosseous integrated implantation: multiple post-extraction implantationing
      threaded cyclindric titanium. Use of a semipermeable reabsorbable membrane].
AB  - On the basis of their experience of postextractive oral grafts, the authors
      examine all the surgical possibilities of this technique, at times using
      osteoinducing materials or at others semipermeable reabsorbable membrane; on
      other occasions an ostroinducing material associated with reabsorbable membrane
      is used to stimulate piloted regeneration of underlying bone tissue. Although not
      widely used, the post-extractive technique is presented as a fascinating reality
      that certainly, if used with due care, produces satisfactory and gratifying
      results. The authors are convinced that the contribution to simplifying surgical
      procedures and the reduced number of sessions that a patient has to undergo is
      without doubt a considerable advantage. In fact, using the postextractive
      technique with reabsorbable membrane the patient only undergoes a single
      operation. The authors have experience of three hundred post-extractive grafts
      with a very low failure rate (loss of seven grafts). These results can be
      attributed to clear rules: respect for antisepsis precautions, minimum surgery
      involving bone tissue, design of access flap to bone arch, positioning of fixture
      in correct spatial and occlusal direction, instant graft stability and
      perioplantar bone neoformation free of interference. The use of grafts has become
      a routine technique and is a valid alternative to prosthetic rehabilitation
      stages. It has become a true field with precise characteristics in the context of
      modern dentistry.

PMID- 8868588
TI  - [Diagnostic and surgical problems in a case of post-traumatic retention of a
      foreign body in the submandibular gland].
AB  - We report a particular case of a traumatically introduced foreign body in the sub
      mandibular gland. A breaking object (plastic pen) penetrated, through the
      anterior oral floor, the submandibular gland. Such foreign bodies should be
      removed before suturing the wounds, as they can disturb healing and cause
      problems long after the accident. An adequate history, clinical and imaging
      studies should reveal the possibility of foreign body penetration and its
      localization, when it isn't previously removed. We compare the use of ultrasound
      detection of foreign bodies in soft tissue and conventional plain radiography,
      computed tomography, and magnetic resonance imaging. The usefulness of US in this
      kind of research does not justify TC or RM studies and allows a less invasive
      surgical operation.

PMID- 8868589
TI  - [Epidermolysis bullosa. Report and discussion of two clinical cases].
AB  - The authors present two clinical cases of epydermolisis bullosa (Hallopeau
      Siemens type), to underline characteristic mucous and dental diseases of these
      types of genodermatosis; they analyze mean diferentiative criteria and the
      diagnostic possibilities; in the specific treatment of this kind of patient it is
      important to focus as the therapeutic approach in the different dental fields: so
      the authors consider therapeutic treatment related to oral and systemic status of
      the patient examined. From this analysis they give a rational way of approaching
      this kind of patient both for hygiene and for diet, surgery-prosthetic and
      restorative treatments.

PMID- 8868590
TI  - [Simultaneous surgical correction of temporomandibular ankylosis and facial
      symmetry. Presentation of a case].
AB  - The authors stress the fact that the clinical course of a monolateral TMJ
      ankylosis tends to be more severe in young people. In this paper we analyze the
      diagnostic procedure for a tridimensional observation of any morphological and
      spatial alteration. The surgical procedure that permits the simultaneous
      correction of ankylosis and associated facial deformities is discussed.

PMID- 8868591
TI  - [Room air allergens: clinical significance, detection and prevention].

PMID- 8868592
TI  - [Different threshold concentrations for sensitization by cattle hair allergen Bos
      d 2 in atopic and non-atopic farmers].
AB  - Several threshold values for indoor allergens leading to IgE sensitization were
      proposed. Currently such values exists for allergens of house dust mite, cat,
      dog, and cockroach and cattle. A high sensitization is known as an important risk
      factor in the development of asthma. This study was undertaken to examine
      threshold values of major cow hair allergen Bos d 2 in the house dust of atopic
      and nonatopic cow hair asthmatic farmers. 45 patients with cow hair asthma were
      visited at their homes. House dust samples were taken from corridor, living room,
      and bedroom. The concentration of Bos d 2 was determined by means of rocket
      immunoelectrophoresis. Additionally, samples of venous blood were taken to
      demonstrate specific IgE towards cow epithelia by CAP-RAST. Five patients were
      excluded from further investigations because they have given up their cattle for
      less than 6 months. In 21 patients occurred typical atopic stigmata like infantil
      history of atopic eczema, hay fever or milk crust, while the other 19 subjects
      did not show an atopic diathesis. High sensitization towards cow epithelia
      (specific IgE > 0.7 kU/l in CAP-RAST) occurred significantly more often in
      atopics than in nonatopics. In atopic subjects the allergen concentrations
      leading to IgE sensitization amounted to 1-20 micrograms Bos d 2/g dust, whereas
      in nonatopics were found higher Bos d 2 threshold values (25-50 micrograms/g
      dust). The present study suggests that in nonatopic cow hair asthmatics high
      indoor Bos d 2 levels lead to IgE sensitization as well as the close contact to
      cattle.

PMID- 8868593
TI  - [Thoracoscopy: current diagnostic and therapeutic indications].

PMID- 8868594
TI  - [Interventional pneumology: procedures for pulmonary hemorrhage and tumor-induced
      superior vena cava syndrome].
AB  - Interventional pneumology includes both bronchological and vascular methods of
      diagnostic and therapy, especially in case of pneumological emergency, such as
      pulmonary hemorrhage and superior vena cava syndrome. In massive pulmonary
      hemorrhage bronchological diagnosis is needed to determine the location and
      activity of the bleeding, as well as angiography of bronchial arteries, and of
      pulmonary arteries, respectively. Bronchus occlusion by aid of balloon catheter
      or double lumen tube are intermediate methods to bridge over till defenitive
      surgery or embolisation of bronchial or pulmonal arteries as complementary
      methods in patients with pulmonary hemorrhage. In patients suffering from
      superior vena cava syndrome caused by neoplasms venous angioplasty and Wallstent
      implantation provide immediate clinical improvement.

PMID- 8868595
TI  - [Differential diagnosis of multiple pulmonary coin lesions--pulmonary hyaline
      granuloma].
AB  - In addition to metastases, the differential diagnosis of pulmonary nodules also
      includes tuberculosis, sarcoidosis, and silicosis. Rarer diseases such as amyloid
      tumors, rheumatic nodules, and plasma-cell granulomas can, depending on the
      clinical situation, be the cause of this finding. For the example of the clinical
      picture of pulmonary hyalinizing granuloma, the differential diagnosis of
      multiple pulmonary nodules is illustrated under consideration of the
      pathognomonic, morphologic observations.

PMID- 8868596
TI  - [Angioleiomyosarcoma of the lung--primary tumor or metastasis?].
AB  - Pulmonary angioleiomyosarcoma was diagnosed in a 69-year-old women by evaluation
      of lung tissue obtained during thoracotomy. The primary angioleiomyosarcoma of
      lung is a very rare leiomyomatous neoplasm of the smaller pulmonary vessels with
      about 100 cases described so far. Sometimes it is difficult to distinguish
      tumorous processes with mainly fibroblastic components and to determine the
      dignity in particular cases. The reliable decision only succides in surgical
      obtained tissue. The clinical course of disease is--like in the presented case-
      determined by recurrence of tumor and metastasis into other regions.

PMID- 8868597
TI  - [The same procedure as every year].

PMID- 8868598
TI  - [Lymph node dissection: staging or therapy? Proceedings of a meeting. Giessen,
      Germany, 1995].

PMID- 8868599
TI  - [The importance of mediastinoscopy for accurate lymph node staging].
AB  - The mediastinoscopy (MS) was developed 1959 by Carlens. Since the introduction of
      computertomography (CT) in the diagnostic of the thorax the MS was no longer used
      routinely. Because of the introduction of the CT in our clinic we performed only
      111 MS between 1981 and 1992, in contrast to 185 MS between 1976 and 1981. No
      patient died perioperatively. Two patients had to be operated on for bleeding.
      The sensitivity of the modern CT-scan for a correct preoperative staging of a
      bronchial carcinoma runs up to 90% and the specifity up to 85%. Therefore a
      correct preoperative staging can only be reached histologically with the help of
      a MS. An exception are T1 and T2 tumors because of only 28% mediastinal lymph
      node metastases. We think that the MS should be performed more often in order to
      reach a correct, histologically ascertained staging preoperatively.

PMID- 8868600
TI  - [Lymphadenectomy in surgery of bronchial carcinoma].
AB  - Since 1982 a total number of 1062 patients underwent surgical treatment of
      bronchogenic carcinoma. There were 972 men and 89 women, with a mean age of 62.5
      years. In 484 cases a squamous cell carcinoma was diagnosed and in 416 patients
      an adenocarcinoma. An alveolar cell carcinoma was found in 54 and a
      polymorphocellular carcinoma in 68 patients respectively. 334 patients were found
      to be in stage I, 233 in stage II and 438 patients were in stage IIIa. The 5-year
      survival rate was 57.2% in stage I and 32.5% in stage II. The group of patients
      with N2 lymph node metastasis according stage IIIa showed a very poor 5-year
      survival rate of 12.3%. A standard therapeutical procedure according to a
      multimodal concept is necessary to improve these patients' long-term survival.
      Systemic lymphadenectomy is essential for adequate therapy.

PMID- 8868601
TI  - [Intrapulmonary tumor cell dissemination and intraoperative pleural lavage as
      prognostic factors in bronchial carcinoma].
AB  - 319 patients with the first manifestation of lung cancer underwent intraoperative
      pleural lavage (lavage I = after opening the chest; lavage II = after resection
      of lung cancer). Tumor cells were found in lavage I in 122 patients (38.2%), in
      94 of them also in lavage II. In only 9 cases we found tumor cells in lavage II
      cytologically. The cumulative five-year survival rate of non-small cell lung
      cancer in stage I (n = 154) was 22.1% if lavage was positive (lavage I and II, n
      = 44), and 64.3% if lavage was negative (n = 110) (p < 0.05). Additionally, we
      performed tissue cultures of tumor-free parenchyma in 23 cases of lung cancer. In
      16 cases (69.6%) we detected tumor cells by histology and immunhistology.
      Intraoperative pleural lavage should be done when assessing the final tumor
      stage. A positive result should be added to the pTNM-classification of lung
      cancer.

PMID- 8868602
TI  - [Lymphadenectomy in bronchial carcinoma: facts and fiction].
AB  - Removal of mediastinal lymph nodes is essential for the surgical staging of lung
      cancer; it is therefore integral part of a curative surgical treatment. The
      accuracy of mediastinal staging - "biopsy" sampling or complete removal of
      mediastinal lymph nodes - is of significance since the N-status affects treatment
      and survival. Anatomical and technical considerations lead to the conclusion:
      Because of the anatomy of the lymph system a complete removal of all draining
      lymph vessels is not possible. However, accurate mediastinal staging is clearly
      recommended over "biopsy"-sampling. Future studies should focus on an improved
      histologic evaluation and should take other "new" factors affecting prognosis
      into consideration.

PMID- 8868603
TI  - [Distribution of lymph nodes and lymph node metastases in esophageal carcinoma].
AB  - BACKGROUND: Lymph node metastases are an independent prognostic factor in
      esophageal cancer. Accurate pathologic work up depends on detailed knowledges of
      number and anatomic distribution of lymph nodes and metastases. Factors that may
      determinate metastatic spread are also important. METHODS: One hundred and fifty
      six patients with esophageal cancer were included in this study. Number and
      localization of nodes and metastases were documented and correlated with
      localization, infiltration deepness and grade of malignancy of the tumor. The
      effectivity of the search for nodes and metastases was also studied. RESULTS: We
      found 3869 lymph nodes containing 338 metastases in the 156 specimens (median 25
      and 2). 53.2% of the cases exhibited metastases and 15.4% contained only solitary
      metastasis. The minimal number of lymph nodes for excluding of metastasis was
      about six nodes. Most of the nodes were found at lower esophagus and on the oral
      stomach resection. Tumors of the middle and upper thoracal esophagus spread also
      frequently to the nodes along the lesser curvature of the stomach. Between
      infiltration deepness and grade of malignancy of the tumors a positive
      association was found. CONCLUSIONS: Lymph node metastases are a frequent
      pathological feature in esophageal cancer which depends on infiltration deepness
      and grade of malignancy of the tumor. This allows the estimation of metastatic
      spread. For staging a minimum of six nodes must be found in the specimen. In this
      context the frequent metastases along the lesser curvature of the stomach must be
      considered.

PMID- 8868604
TI  - [Value of 2-field lymphadenectomy in intrathoracic esophageal carcinoma].
AB  - Surgical procedures including the extent of systematic lymphadenectomy are still
      under discussion in the treatment of esophageal cancer. In the own patients'
      population 92 subtotal en bloc-esophagectomies with a standard two field
      lymphadenectomy were performed. A total of 1483 lymph nodes were resected in the
      thoracic and abdominal compartments with an incidence of 16.1% being metastatic.
      Stage pN1 disease occurred in 57.6% of the patients. The median number of lymph
      nodes resected in each specimen was 16, independent of tumor stage, -site or R
      classification. The number of infiltrated nodes increased with tumor stages. R
      classification, tumor stage and number of involved lymph nodes could be analyzed
      as prognostic factors. After R0-resection a median survival rate of 25.4 months
      could be achieved, following pN0-stage that of 27.4 months. In case of two
      metastatic lymph nodes the prognosis decreased significantly to 14.4 months (p <
      0.01). Therefore, two field lymphadenectomy may show a therapeutic benefit only
      in a subgroup of patients with a limited number of lymph nodes infiltrated.

PMID- 8868605
TI  - [Systematic lymphadenectomy in esophageal carcinoma--preliminary results of a
      prospective randomized study].
AB  - The influence of transhiatal blunt esophagectomy with dissection of all reachable
      lymph nodes (ESD) and en-bloc-esophagectomy (EB) on perioperative cardio
      pulmonary stress and late results was analysed in a prospective randomized trial.
      Blunt dissection of the esophagus was performed without systematic lymph node
      dissection (SD) in patients with increased cardio-pulmonary dysfunctions. Until
      now 26 patients (ESD: 13, EB: 13) entered the study as well as 14 patients
      treated by blunt dissection. The number of dissected lymph nodes in each patient
      was 7.5 (SD), 19.9 (ESD) and 37.6 (EB). Ratio of invaded to removed lymph nodes
      was 0.26 (SD), 0.25 (ESD) and 0.1 (EB). The 30-day mortality rate was 8.0% in
      each group. Under the consideration of this mortality, one-year survival rate was
      79% (SD), 70% (ESD) and 77% (EB). Patients with negative lymph node involvement
      showed a one-year survival of 85% and positive involvement lead to a survival
      rate of 70% after one year, independently of the surgical approach.

PMID- 8868606
TI  - [Value of systematic lymphadenectomy in stomach carcinoma].
AB  - In a retrospective study of 157 patients undergoing a curative resection of a
      gastric carcinoma between 1982 and 1992 the correlation of the lymph node status
      and histomorphologic parameters of the gastric cancer and the significance of the
      systematic lymphadenectomy were analysed. The patients were divided into two
      historical groups (exclusively D1- and systematic D1-/D2-lymphadenectomy). Among
      the histomorphological parameters only the depth of infiltration (pT) revealed a
      high correlation with the extent of metastatic lymph node involvement. Tumor
      form, Lauren-classification and tumor localisation only showed a marginal
      influence on the nodal status. The overall 5-year survival rate was not
      significantly changed by the systematic lymphadenectomy, only the subgroup of the
      UICC-stadium II demonstrated a small benefit. The extended systematic lymph node
      dissection did not rise the complication rate but lowered the rate of local
      recurrences. In conclusion, the indication for a systematic lymphadenectomy
      cannot be deducted from the constellation of different histomorphological
      parameters, but the feasibility of a systematic lymphadenectomy results from the
      improvement of staging and survival rate at least for the UICC-II-stadium and the
      reduction of local recurrences.

PMID- 8868607
TI  - [Reliability of intraoperative macroscopic evaluation of lymph node metastasis
      and effectiveness of lymphadenectomy in stomach carcinoma].
AB  - The aim of this prospectively performed study was to evaluate the accuracy of
      macroscopic intraoperative lymph node staging by the operating surgeon. 65
      patients with histologically proven gastric carcinoma and without previous
      abdominal operations were included. Carcinomas of the cardia and malignant
      lymphomas were excluded. Due to the study protocol the surgeon evaluated the
      lymph node status before beginning the resection. For exact exploration of the
      compartments II and III the omental bursa had to be opened through the
      gastrocolic ligament and the lesser omentum had to be cut off from the liver. The
      resection itself consisted of en bloc total gastrectomy, D2 lymphadenectomy and
      removal of the lesser and the greater omentum. The operation was completed by the
      removal of the spleen if necessary. The surgeon thought 85.2% of the N0-patients
      to be N > 0 and overlooked lymphatic occupation of compartment I in 8.8%, of
      compartment II in 14.3% and of compartment III in 50%. The histological
      examination of the resection specimen showed that the surgeon's impression
      concerning the extent of the lymph node occupation of the complete situs was
      correct in only 16.9%. The allocation of the macroscopically determined lymph
      node status to the TNM scheme was correct in 33.8%. It should be concluded from
      the study that intraoperative macroscopic staging procedures as a basis for
      therapeutic decisions are to be avoided strictly.

PMID- 8868608
TI  - [Systematic lymphadenectomy in stomach carcinoma--staging and therapy].
AB  - The diagnostic and therapeutic relevance of systematic (D2-) lymphadenectomy was
      studied in 440 resections for primary gastric carcinoma. A total of 13910 lymph
      nodes (mean: 31.6 (15.3)) was resected with 3716 being metastatic (mean: 8.6
      (11.0)). During surgery 24% of the carcinomas were incorrectly staged when
      compared with the pathological stage. The prognosis was influenced by tumor
      stage, R-classification and number of lymph node metastases. Patients with a
      maximum of three metastases and R0-resection had a prognosis not significantly
      different from patients with pN0-stage (5-year-survival: 77% and 64% resp.; p =
      0.21). Systematic lymphadenectomy in gastric carcinoma has not only diagnostic,
      but also therapeutic importance in patients with limited lymph node metastases.

PMID- 8868609
TI  - [Value of radical lymph node dissection (compartment I and II) in stomach
      carcinoma].
AB  - In a prospective multicentre study of 2394 patients with gastric carcinoma the
      prognostic relevance of systematic lymph node dissection was evaluated. Of 1654
      patients undergoing resection, 558 had a standard lymph node dissection, defined
      as fewer than 26 nodes in the specimen, and 1096 underwent radical
      lymphadenectomy, i.e. 26 or more nodes in the specimen. Radical dissection
      significantly improved the survival rate in patients with Union Internacional
      Contra la Cancrum (UICC) stages II and IIIA tumors. Multivariate analysis
      identified radical dissection as an independent prognostic factor in the
      subgroups of patients with UICC tumor stages II and IIIA. Radical dissection
      conferred no survival advantage in patients with pN2 tumors. There was no
      significant difference in morbidity and mortality rates between radical and
      standard lymph node dissection. Radical lymphadenectomy improves survival in
      patients with UICC gastric cancer stages II and IIIA, and should be the
      recommended treatment for such patients.

PMID- 8868610
TI  - [Advantages of lymph node staging in 872 stomach carcinoma patients].
AB  - The German Stomach Cancer TNM Study Group registered 1444 patients from 1982 to
      1984 in a multicenter observational study to validate the tumor node metastasis
      stage groupings. The follow-up-rate in 1989 was 99.4%. Among others the pattern
      of lymph node metastases and the benefit of systematic lymphadenectomy (SLA) was
      studied. 872 patients had a resection with or without lymph node staging lymph
      node metastases were under- or overestimated intraoperatively in 7-23%. More than
      expected lymph nodes distant from the primary were involved. The survival rate of
      patients with resected tumors in the distal third of the stomach could be
      evaluated. We found statistically significant benefit for stage I (UICC 1987) of
      patients resected with SLA vs. without: 86% respectively 66%. The conclusions are
      as follows: lymph node involvement is numerous, widespread and also far away from
      the tumor. The intraoperative statements about lymph node metastases are
      doubtful. The R0-resection includes the SLA which is improving the survival rate
      for stage I.

PMID- 8868611
TI  - [Is splenectomy "en principe" necessary for radical gastrectomy with systematic
      lymphadenectomy?].
AB  - SUMMARY: In order to screen the necessity of splenectomy "en principe" we
      evaluated all patients suffering from gastric carcinoma between Jan. 1988--Apr.
      1993 retrospectively. In total a group of 318 patients were treated and from
      these 261 patients were operated (resection rate 82%). In 30% of the patients (77
      pat.) we performed a subtotal distal gastrectomy and in 70% (184 pat.) a radical
      gastrectomy with a D 2-lymphadenectomy. The splenectomy rate in the group of
      gastrectomy was 94% (173 pat.). In total 13% of the lymph nodes of the hilus of
      the spleen were infiltrated and an additional metastasis of the spleen was found
      in 1%. In carcinomas located at the minor curvature 13% had an infiltration of
      the lymph node station 10, in carcinomas located at the greater curvature in 17%
      and in carcinomas with a diffuse tumor growth in 10% respectively. Patients with
      a tumor located in the proximal stomach had an infiltration of the lymph nodes in
      14% and in carcinomas of the antrum in 7% respectively. None of the patients
      having a UICC stage I/II had an infiltration of the lymph nodes at the hilus of
      the spleen, but 25% of the patients having a UICC stage III/IV. 2 patients from
      the latter group had an additional metastasis of the spleen. CONCLUSION: The
      indication of splenectomy is given only in advanced proximal tumor locations,
      especially in tumors of the greater curvature. In the early tumor stages and in
      the distal locations of gastric carcinoma it might be useful to perform a
      selective lymph node dissection of the hilus of the spleen in order to increase
      the completeness of the radical gastrectomy.

PMID- 8868612
TI  - [Historical development of the Thuringen Society of Surgery].

PMID- 8868613
TI  - [Current TNM staging: 1. Clinical significance and current status. The German
      Speaking TNM Committee].

PMID- 8868614
TI  - The gender analysis imperative: introduction to the special issue.

PMID- 8868616
TI  - Sexuality and reproductive health care in Sao Paulo, Brazil.
AB  - Gender inequalities influence the quality of reproductive health care in many
      ways. The lack of gender sensitivity in the provision of activities related to
      illness prevention and health care, as well as women's difficulties in
      controlling their own sexuality, are fundamental aspects of this problem. Two
      recent studies carried out in Sao Paulo, Brazil, examined factors associated with
      the use of methods to control fertility and to prevent STDs/AIDS. Both studies
      identified a strong resistance to extending the use of barrier methods among the
      female population, even though doing so is particularly important to help contain
      the spread of HIV/AIDS among women in this country. Findings include that gender
      sensitive strategies must be developed to stimulate the process of behavior
      change. These strategies should be combined with holistic approaches to women's
      health care, so that prenatal and gynecological care, family planning, cervical
      cancer screening, and STDs/AIDS prevention are included within the same program.

PMID- 8868615
TI  - Evaluating rural Bangladeshi women's perspectives of quality in family planning
      services.
AB  - Several frameworks for understanding the quality of family planning care have
      been proposed. However, efforts to measure and quantify their components remain
      underdeveloped, especially with regard to nonclinical care and community-based
      distribution. This study examines a large-scale field survey conducted among
      married women of reproductive age in rural Bangladesh in 1989 and 1990 to measure
      and evaluate rural women's perceptions of the quality of outreach services they
      received. Initial analysis indicates that rural women are able to distinguish
      between good and poor quality of care and that these perceptions can be
      accurately documented and quantified through sample survey approaches.
      Implications of the use of a survey in the measurement of quality of care are
      discussed, as well as implications of the results for managers within the
      Bangladesh government family planning program, which has been regarded by donor
      agencies as having limited responsiveness to clients' needs.

PMID- 8868617
TI  - The assessment of reproductive health services: a conceptual framework for
      prenatal care.
AB  - This article delineates a conceptual model for defining and measuring quality in
      prenatal services. It addresses three issues related to women's health: (a) the
      emerging interest in reproductive health as a concept that encompasses the full
      range of women's needs, versus the more narrow concept and approach of
      traditional maternal and child health services; (b) the importance of prenatal
      services within the context of reproductive health, particularly in developing
      countries; and (c) the positive role that quality plays in promoting women's
      health. It then proposes a model for defining and measuring quality in prenatal
      services, styled after Donabedian's work and informed by Bruce's framework. It
      assesses the quality of prenatal care in terms of five elements: management,
      pregnant woman-provider relations, technical competence, information
      transmission, and continuity of care. The framework was tested in the city of
      Irbid, Jordan, in 1992. Findings are summarized, and recommendations for future
      work as discussed.

PMID- 8868618
TI  - Quality of care for women in northeast Thailand: intersections of class, gender,
      and ethnicity.
AB  - Based upon ethnographic fieldwork in a rural village community in Northeast
      Thailand, this article explores issues relating to the quality of care received
      in reproductive health services from the perspective of village women.
      Inequalities of power fundamental to gender, class, and ethnic relations are
      described as elements affecting the service-giving process. The subordinate
      position of village women is subtly reinforced in the spatial organization, style
      of communication, and management of the services.

PMID- 8868619
TI  - Quality health care for women: a global challenge.
AB  - This paper discusses barriers to the provision of high quality care from the
      perspectives of the health system and female clients, and interventions that have
      been developed to overcome these barriers. These interventions are in the area of
      reproductive health, where most attention to women's health has focused; they
      consist mainly of assessment tools that can be used by peripheral health workers
      and rural women themselves. The paper argues that in nonreproductive health
      generally, there is a dearth of information on the biological and social
      determinants and consequences of infection and disease from a gender perspective.
      Recommendations are made for further research on quality of care and for
      practical interventions with application to women's health, both within and
      outside the reproductive context.

PMID- 8868620
TI  - Gender inequity: an issue for quality assessment researchers and managers.
AB  - This article explores the question of whether the issue of gender inequity can
      and should be included in the different models of quality assessment gaining
      ground internationally. The discussion is divided into three parts: reflections
      on some of the conceptual issues that justify research on gender equity in health
      services; a brief review of the literature that provides empirical data in this
      area; and comments on the challenges faced by researchers in this field, and
      possible ways to incorporate gender indicators into quality assessment research
      and management.

PMID- 8868621
TI  - Making women and men matter: the Philippine POPCOM experience.
AB  - To reorient population policies and programs and make population workers more
      gender-responsive was the challenge faced by the Philippine Population Commission
      (POPCOM), the government's central policymaking and coordinating body for
      population concerns. This paper traces the history of population policies in the
      Philippines and describes the factors that helped create a climate conducive to a
      rethinking of POPCOM's policies. POPCOM first conducted an institutional
      assessment to determine the levels of awareness of its population officers about
      gender, reproductive health, and population and development issues. A gender
      responsive population policy framework with a reproductive health perspective was
      then developed to guide training programs, information management strategies, and
      pilot community-based action research programs. Problems anticipated in
      integrating a gender and reproductive health perspective include the Catholic
      Church, different priorities of government, and a reluctant Congress. Suggested
      strategies are (a) formation of a critical mass of various groups to demand
      policy shifts; (b) for women, development, and environment nongovernmental
      organizations to identify allies in government and international organizations;
      (c) regular dialogues between donors and the government's central planning
      agency; and (d) working through the media.

PMID- 8868622
TI  - Asking simple questions: promoting continence (repeat) (continuing education
      credit).

PMID- 8868623
TI  - Perinatal group B streptococcal infections: the nurse's role in identification
      and prophylaxis.
AB  - Group B Streptococcus (GBS) is a major cause of perinatal infectious morbidity
      and mortality in the United States. An estimated 50,000 women and 7,600 neonates
      experience GBS disease, and as many as 310 infants die each year. In 1992, the
      American Academy of Pediatrics published recommendations for identification and
      treatment of pregnant women colonized with GBS. In 1996, the Centers for Disease
      Control and Prevention and the American College of Obstetricians and
      Gynecologists developed more comprehensive guidelines. The article describes the
      central role of perinatal nurses in the identification of pregnant women
      colonized with GBS, patient education about GBS disease, and successful
      implementation of intrapartum GBS prophylaxis.

PMID- 8868624
TI  - Varicella infection and toxoplasmosis in pregnancy.
AB  - Varicella occurring in pregnancy can be dangerous for the fetus, the mother, and
      the newborn. The fetus may experience multiple system damage. The mother and
      newborn are at increased risk for varicella pneumonia with a 9% and 20% fatality
      rate, respectively. The recent introduction of the varicella vaccine will affect
      the occurrence of gestational infection. Toxoplasmosis is rarely dangerous for
      the pregnant woman, yet the fetus and newborn may be at risk for chorioretinitis,
      hydrocephalus, intracranial calcifications, and convulsions. The greatest
      challenge in the management of toxoplasmosis in pregnancy is diagnosis of the
      asymptomatic newborn before damage occurs. Strategies to prevent toxoplasmosis
      should be taught to every pregnant woman as part of parental care.

PMID- 8868625
TI  - The effects of human parvovirus B19 and cytomegalovirus during pregnancy.
AB  - Human parvovirus B19 and cytomegalovirus (CMV) are two common viruses that can
      have significant and devastating effects on a fetus. Maternal infection may lead
      to vertical transmission of the virus to the fetus. Parvovirus infection in the
      fetus may cause miscarriage, nonimmune hydrops, or demise. Fetal CMV infection
      can cause a number of problems, including nonimmune hydrops and neurosensory
      disabilities. Nurses who are knowledgeable about possible viral effects during
      pregnancy can collaborate in the management of these patients, particularly in
      the areas of patient assessment, education, and support.

PMID- 8868626
TI  - Prevention of hepatitis B and C transmission during pregnancy and the first year
      of life.
AB  - Hepatitis B (HBV) infection is readily transmitted from infected mothers to their
      infants at birth. An estimated 22,000 HBV carriers give birth in the United
      States annually. HBV infection is more than 95% preventable if exposed infants
      receive hepatitis B immune globulin and HBV vaccine at birth. Current guidelines
      recommend testing of all pregnant women for hepatitis B surface antigen to detect
      infection and ensure prophylaxis of infants. The risk of perinatal transmission
      of hepatitis C (HCV) infection appears to be small, except in women coinfected
      with human immunodeficiency virus or with high viral titers. Currently, there is
      no licensed vaccine against HCV, although several are in development.
      Postexposure treatment with immunoglobulin is of no proven benefit in preventing
      HCV infection.

PMID- 8868627
TI  - Percutaneous central venous catheters in neonates: a descriptive analysis and
      evaluation of predictors for sepsis.
AB  - The article describes the experience with percutaneous central venous catheters
      in 565 neonates with birth weights of 400 to 6810 g. The catheter-related sepsis
      incidence was 19.1%, or 13.5 infections per 1000 catheter days. By discriminant
      function analysis, 86% of all neonates studied were correctly classified into the
      confirmed sepsis and no sepsis groups on the basis of six predictor variables.
      The model did not accurately predict the neonates who would develop confirmed
      sepsis. The weight at catheter insertion and length of time for which the
      catheter was in place were identified as variables that contributed significantly
      to differentiation between sepsis and no sepsis groups.

PMID- 8868628
TI  - Respiratory syncytial virus infection in infants: a significant challenge for
      optimal care.
AB  - Respiratory syncytial virus (RSV) is a potent pathogen causing annual epidemics
      of serious illness in young infants. Controversy over interventions has evolved
      given conflicting research results concerning the disease process and the variety
      of treatment options. Investigations over the last two decades have provided more
      insight into the complexity of this sometimes deadly infection and better
      understanding of the reasons why treatment is so elusive. Currently, RSV
      infection cannot be prevented, and there is no definitive cure. The article
      discusses the pathophysiology of RSV and provides a description of the available
      treatment approaches currently in use and those under development.

PMID- 8868629
TI  - Health care, politics, and nursing.

PMID- 8868630
TI  - Advanced-practice nurses: approaches to collaborative research.
AB  - The collaborative approach to research can prove effective for the advanced
      practice nurse (APN). While there are a number of ways to deal with research
      collaboration, this article discusses the hierarchial, consultative, and
      council/consortium models. In addition, the article addresses specific guidelines
      for establishing collaborative research, delineates the organizational support
      needed to implement such projects, and offers three possible research foci
      (outcomes research, case management research, and population-specific research).

PMID- 8868631
TI  - Ethical responsibility in health care reform dialogue.

PMID- 8868632
TI  - Coping with clinical site shortages.
AB  - The shrinking number of nursing clinical sites and the backlog of nursing
      students in generic programs waiting for clinical placement present major
      problems in nursing education. Positioning the clinical practicum of generic
      nursing programs in the final year of the curriculum is suggested. Advantages and
      disadvantages are discussed.

PMID- 8868633
TI  - New ANA guidelines for ethics in nursing research.

PMID- 8868634
TI  - CQI applications in a community hospital.
AB  - Through the use of a data-driven system utilizing a Continuous Quality
      Improvement (CQI) model developed by QualPro Corporation, a community hospital
      has impacted both administrative and clinical areas of practice. The use of
      QualPro's Eight-Step Method for Quality Improvement provides ongoing data to
      support and change nursing practice in these settings. The CQI process promotes
      collaborative practice for all practioners and has led to greater provider
      satisfaction.

PMID- 8868635
TI  - Environmental factors and nutritional status of rural children.
AB  - The nutritional status of school-aged children is a growing concern of health
      care professionals today. In collaboration with a Kellogg Project in the deep
      south, students from a large university school of nursing participated in a
      project to improve the nutritional status of rural school-aged children. The
      project goals focused on educating thd children about the U.S. Department of
      Agriculture (USDA) Food Guide Pyramid, reading nutritional labels and recognizing
      foods with high fat content, and the importance of exercise along with diet. The
      nursing students created a nutritional assessment tool to use with each child to
      determine their educational needs. The project involved lecture, interactive
      class discussion, and hands-on activities. Information from the assessment tool
      revealed that fast food and foods high in fat were the most popular with the
      children. After project completion, the posttest revealed an increase in
      cognitive knowledge of nutrition among all the children. In addition to this
      positive learning experience for the children, improving the health status of
      children in the community was an excellent educational opportunity for the
      nursing students.

PMID- 8868636
TI  - Definition and management of anxiety, agitation, and confusion in ICUs.
AB  - Critically ill patients require continuous assessment of their need for sedation
      and pain management. The purpose of this study was to develop a consistent
      categorization of patient's symptoms and to identify actions that yield effective
      patient outcomes. Nurses in this study described patients with sedation problems
      as those who were disoriented or aggressively acting out, fearful and restless,
      or manifesting changes in orientation, memory loss, or mental status. Twenty
      seven medical intensive care unit (MICU) nurses volunteered to complete a
      questionnaire about their assessment process in determining patient's sedation
      needs, interventions, and evaluation criteria for patient outcomes. Fifty-five
      patient questionnaires were completed by the nurses. Nurses identified separate
      subjective and objective cues for patients' anxiety, agitation, and confusion.
      The most frequently identified nursing actions were assessment to differentiate
      between pain, anxiety, agitation, and confusion; personal reassurances,
      relaxation and other physical comfort techniques; administer prescribed
      medication; collaborate with a physician to identify cause; and give additional
      prescribed medication. Effective outcome measures included stable vital signs,
      normal oxygen saturation, progression with ventilator weaning if appropriate,
      return to normal level of orientation, and a quiet yet arousable state.

PMID- 8868637
TI  - 'Chronic life'.

PMID- 8868638
TI  - A time of nursing opportunity.

PMID- 8868639
TI  - Integrating care for people with chronic conditions.

PMID- 8868640
TI  - Remaking chronic-care services. Interview by Patricia Jakobsen.

PMID- 8868641
TI  - Celebrating the journey.

PMID- 8868643
TI  - [A file for the specific care of the aged].

PMID- 8868644
TI  - [The price of success of organ grafts, a cruel shortage of grafts].

PMID- 8868645
TI  - [Brain death: "a special resuscitation"].

PMID- 8868646
TI  - [Bone marrow donation, donation of life].

PMID- 8868648
TI  - [Total hip replacement, a recent French revolution].

PMID- 8868647
TI  - [Anti-cancer drugs. 2].

PMID- 8868649
TI  - [Walking: unimaginable happiness].

PMID- 8868650
TI  - [Depressive troubles before puberty].

PMID- 8868651
TI  - [Distance: nurses facing AIDS...].

PMID- 8868652
TI  - [The nurse's role in secondary cerebral stress of systemic origin].

PMID- 8868653
TI  - [Infection, a constant and current danger].

PMID- 8868654
TI  - [Septic shock of the newborn].

PMID- 8868655
TI  - [Accreditation. Notes on a project].

PMID- 8868656
TI  - [Care of skin infections in patients in peritoneal dialysis].
AB  - The incidence of exit-site infections among peritoneal home-dialysis patients was
      quantified following for 1 year all home dialysis patients of 23 dialysis
      centres. The exit site conditions were observed and classified according to
      Twardowsky. When an infection occurred data on its treatment were collected. 393
      patients were observed. The infection occurred in 40 patients (10.1%). 82.2% of
      patients wear a Tenckoff catheter, 3% do not protect the exit site with any kind
      of dressing. The strategies adopted by different centres vary for the choice of
      antiseptics, the suggested frequency of changes dressing and the routine use of
      nasal swabs. Due to the limited number of patients with infection no association
      was found between tunnel direction or frequency of dressing changes and
      infections occurrence. Discussion on controversial aspects and the definition of
      common guidelines for instance for frequency of dressing changes, use of
      antiseptics is warranted.

PMID- 8868657
TI  - [Home care of children with chronic diseases: cooperation between hospital and
      home care workers].
AB  - Newborns with chronic problems needing continuous and special care even after
      discharge are not very frequent but represent a challenge for the caring team.
      The discharge program of the Neonatal Care ward of Trento hospital includes
      several steps: discharge meetings of teh neonatologist and the nurse responsible
      for the child, the head nurse, the psychologist and, when possible, the social
      worker; a training program for the parents; the coordination of communications
      and interventions of the home-care nurses and a detailed post-discharge planning.
      From 1995 a home-hospital program, as an alternative to the hospital admission
      was started. To describe how the team functions and stress the need of a close
      integration among the team members, the case of Ahmed is presented. This case
      faced the team with several challenges, because of the lack of parent's knowledge
      of the italian language and of the severity of the child's problems. Every care
      plan is developed building on newborn's needs and patients' resources. Data on
      the patients-problems dealt with from 1991 to 1995 and the interventions and
      resources needed are presented.

PMID- 8868658
TI  - [Epidemiology of anxiety in the hospital].
AB  - A very common though very often neglected problem is the anxiety among
      hospitalized patients. A group of nurses of the Matera hospital tried to quantify
      the prevalence of such a problem collecting data on patients treated during the
      hospital stay, admitted or discharged with a prescription of tranquillizers. Over
      941 patients observed, 59 (6.2%) were treated with benzodiazepines, neuroleptics
      or antidepressants, the prevalence being higher in the medical wards (8.9%) than
      in the surgical ones (4.5%). The problem most commonly treated in the medical
      wards is the anxiety and the insomnia in the surgical wards. The most frequently
      prescribed drugs (47 patients, 79.6%) are the benzodiazepines. This is one of the
      first attempts to quantify the prevalence of anxiety in an hospital population.
      Although number of patients treated is limited the overall management of anxiety
      can be improved.

PMID- 8868659
TI  - [When the hospital affects life].

PMID- 8868660
TI  - [Methods and instruments of research: analysis of several articles].
AB  - Research papers published on some of the most well known nursing journals are
      presented and discussed. The main aim of the contribution, which opens an arena
      for discussion on the Rivista dell'Infermiere is to critically appraise published
      research works focusing both on strengths and novelty and weaknesses in the
      hypothesis formulation, methods and instruments used, discussion of results. A
      critical analysis should enable nurses to start learn to read and eventually
      write a research protocol, possibly avoiding some common mistakes.

PMID- 8868661
TI  - [Measurement of the workload in nursing].

PMID- 8868663
TI  - [The health of immigrants and the nurse's role].

PMID- 8868662
TI  - [Children and venipuncture].

PMID- 8868666
TI  - Doctors 'did not consult'.

PMID- 8868667
TI  - Nursing students get harder to find.

PMID- 8868664
TI  - [Let my daughter work].

PMID- 8868668
TI  - Tackling abusers.

PMID- 8868669
TI  - Here to there.

PMID- 8868670
TI  - Strict watch.

PMID- 8868671
TI  - The beginning of the end?

PMID- 8868672
TI  - Creating the passage.

PMID- 8868673
TI  - The Sheffield Centre for Health and Related Research.

PMID- 8868675
TI  - Educating nurses to undertake clinical supervision in practice.
AB  - Alongside interest in the process of clinical supervision, there is a growing
      recognition of the need for education for practitioners undertaking the role of
      supervisor. This article describes a module accredited by the Welsh National
      Board and the University of Wales, Swansea, which was designed to achieve this
      aim and help practitioners design structures for supervision applicable to their
      practice settings. The structure and content of the module are described, as well
      as an evaluation of the first intake.

PMID- 8868674
TI  - Nurses' perceptions of roles in multidisciplinary teams.
AB  - The move towards multidisciplinary approaches to health care has been encouraged
      by a number of government reports (DoH 1986, 1989) in order to support the
      increase in community care and improve the quality of the service. Such
      approaches to care are dependent on a high level of co-operation between members
      of different professions within the multidisciplinary team. Inherent in the
      concept of such a team is the assumption that each team member has a clear
      understanding of the role of all other members. This project set out to test this
      assumption by examining the knowledge and perception of nurses and podiatrists
      with regard to each other's role.

PMID- 8868676
TI  - Understanding the conflicts of patient empowerment.
AB  - In line with the emphasis placed by nursing development units on critical
      scrutiny and practice evaluation, the authors review the patient empowerment
      nursing literature to identify its practical implications for their clinical area
      and staff. This article presents some early conclusions arising out of this
      process and highlights the conflicts which nurses face in ensuring that patients
      are empowered while maintaining their rights and privacy.

PMID- 8868677
TI  - Tissue viability. Using non-invasive methods to perform vascular assessment.

PMID- 8868678
TI  - Tissue viability. Living with leg ulcers: a patient's personal experience.

PMID- 8868679
TI  - Tissue viability. Leg ulcer care: the need for a cost-effective community
      service.

PMID- 8868680
TI  - Tissue viability. Leg ulcer care: auditing the service in the community.

PMID- 8868681
TI  - Tissue viability. Defining the number of cavity wounds in the community.

PMID- 8868682
TI  - States study scope of practice and reimbursement.

PMID- 8868683
TI  - Trilateral initiative addresses international cooperation.

PMID- 8868684
TI  - Professional accountability forms the foundation of professional development.

PMID- 8868685
TI  - Texas creates a profile of the disciplined professional nurse.

PMID- 8868687
TI  - Raising awareness of professional boundaries and sexual misconduct. Nursing
      faculty are encouraged to take a proactive role.

PMID- 8868686
TI  - Colorado State Board of Nursing looks at education program approval.

PMID- 8868688
TI  - Highlights: First International Pan American Congress on Nosocomial Infections.

PMID- 8868689
TI  - Infection prevention in the operating room.

PMID- 8868690
TI  - Universal precautions.

PMID- 8868691
TI  - Infection prevention update.

PMID- 8868692
TI  - The nurse of the 1990s: not too bright, believes in voodoo, often kills patients.

PMID- 8868693
TI  - The history of the neonatal nurse practitioner in the United States.
AB  - Emergence of the neonatal nurse practitioner role in the 1970s was influenced by
      improved care for high-risk neonates, the expanding role of neonatal nursing,
      medical staff shortages, and the nurse practitioner movement. The role continued
      to evolve in the 1980s and 1990s. This article chronicles the development of the
      neonatal nurse practitioner role, education, and certification.

PMID- 8868694
TI  - A descriptive study of current neonatal nurse practitioner practice.
AB  - This study describes the role of the neonatal nurse practitioner (NNP) in current
      practice and identifies facilitators and constraints to practice perceived by
      individuals currently practicing as NNPs. The 7-point scale used in this study
      allowed respondents to identify specific conditions of NNP practice, from highly
      facilitating (+3) to very constraining (-3). Each item was followed by a
      clarification section. The questionnaire was mailed to 1,521 individuals holding
      current NNP certification in the U.S. Data were analyzed using a total
      facilitation score. The possible range for this score (+225 - (-)225) is based on
      the numerical range of the scale (+3 - (-)3) multiplied by the 75 items in the
      facilitation section of the questionnaire. Actual scores ranged from +195 to 
      114, indicating that NNPs are more facilitated than constrained in their
      practice. Empirical data generated by this study will help in developing a
      theoretical model for NNP practice and provide important information for shaping
      the future role of the NNP.

PMID- 8868695
TI  - Evaluation of the neonatal nurse practitioner role: the next frontier.
AB  - The neonatal nurse practitioner (NNP) role at Dartmouth Hitchcock Medical Center
      in Lebanon, New Hampshire, has been in place since 1989. As part of the
      professional growth and development of this NNP group, the necessity for a useful
      evaluation instrument emerged. This instrument needed to be congruent with the
      job description, practice philosophy, and strong commitment to peer review. The
      literature search and institutional survey failed to uncover an acceptable
      option, so an evaluation instrument was developed, tested, and refined. This
      instrument captures the diverse scope of NNP practice and incorporates a
      continuum of novice to expert competencies based on the work of Patricia Benner.
      This evaluation mechanism has had a profound effect on our group, encouraging the
      development of a shared vision of the NNP role and stimulating professional
      growth.

PMID- 8868696
TI  - Parent information binder: individualizing education for parents of preterm
      infants.
AB  - To assist the parents of preterm infants at Mount Sinai Hospital, Toronto,
      Canada, we have developed a unique and creative method of individualizing parent
      information: The parent information binder (PIB). This method has supported a
      shift from nurse-directed education to parents as partners in their own
      education. Parents and health care professionals utilize the PIB collaboratively
      to facilitate organization and collection of information, which is individualized
      according to the infant's level of wellness and the parents' readiness to receive
      the information. This approach empowers parents to be active and integral
      participants in decisions regarding their infants' hospital care.

PMID- 8868697
TI  - Fight over postpartum hospital stays.

PMID- 8868698
TI  - Nurse education in Pakistan.

PMID- 8868699
TI  - Regional neonatal follow-up program.

PMID- 8868700
TI  - Lumbar puncture and evaluation of cerebrospinal fluid.

PMID- 8868701
TI  - Developmental competencies for staff in the NICU.

PMID- 8868702
TI  - Can I look at my baby's chart?

PMID- 8868703
TI  - Kelley's story.

PMID- 8868704
TI  - Rationing and unfairness in the National Health Service: who is responsible, who
      is to blame and what can be done about it?

PMID- 8868705
TI  - Nurse supervisors' views of their supervisory styles in clinical supervision: a
      hermeneutical approach.
AB  - The purpose of this paper is to describe and analyse the nurse supervisors'
      styles with special focus on their actions in the supervision session, their
      expectations with regard to the 'ideal' supervisor and their 'visions' regarding
      effects of clinical supervision, as well as their views of ethics, rules and
      values that they are guided by in clinical supervision. This study used a
      hermeneutic approach in order to characterize nurse supervisor style. Data were
      collected by open-ended interviews with skilled and experienced nurse supervisors
      (n = 18). The interpretation is that the supervisors' actions in clinical
      supervision may affect their ability to understand their actions. Whether a
      supervisor acts as the 'real' supervisor or attains to the level of the 'ideal'
      supervisor depends on her/his state of preparedness reached through reflection.
      The nurse supervisors' perceptions of styles are: striving to perfect the art of
      communication in the supervision session by using selected techniques; to assist
      in increasing the supervisees' self-esteem and autonomy by reflecting on
      essential themes in the supervision dialogue; and striving to attain the level of
      the 'ideal' supervisor, expressing a positive attitude to and motivation for
      theoretical and practical knowledge, and developing the supervisees' human
      attitudes.

PMID- 8868706
TI  - Pragmatism and change: some implications for nurses, nurse managers and nursing.
AB  - 'Change' is a concept currently enjoying much debate and analysis within nursing.
      Most of this debate and analysis has occurred on a purely academic level:
      academic examinations of change, however, do not necessarily help nurses
      understand the mechanisms behind change nor, more importantly, do they
      necessarily help nurses manage change any better. There is, as such, an argument
      for the adoption of a more pragmatic approach to change. This paper takes such an
      approach. The author argues that a greater understanding of change can be gained
      by examining some of the more fundamental characteristics of change, by comparing
      and contrasting successful and unsuccessful examples of change and by viewing
      change as a fluid rather than static entity. A pragmatic approach also reveals
      the potential of action research as an aid to the understanding of change and as
      a tool for implementing change in the three distinct spheres of nursing
      considered: the cognitive-behavioural (personal) sphere, the discipline-wide
      (professional) sphere and the organizational (managerial) sphere.

PMID- 8868707
TI  - District nursing and the National Health Service reforms: a case for
      clarification.
AB  - The challenges to the district nurse's role within the purchaser/provider culture
      of the National Health Service (NHS) are discussed. The inherent problems of
      describing community working and the seeming invisibility of what district nurses
      do is placed in the context of GP fundholding, contracting and commissioning. The
      paper concludes that district nursing's history of not being involved in policy
      development and change may lead to it losing aspects of patient care that is well
      placed and qualified to deliver.

PMID- 8868708
TI  - Individual flexibility: an essential prerequisite in arranging shift schedules
      for midwives.
AB  - The irregular shift system in Finnish hospitals with schedules traditionally
      planned for short 3-week periods creates problems in the social life of the
      personnel. Current backward rotation with 'quick returns' and rest periods
      between the shifts which are too short cause fatigue. The possibilities provided
      by legislation for individual and functional flexibility in the planning of
      schedules have not been utilized because of the hierarchical structure of
      hospital organizations. This study was aimed at finding measures to reduce the
      strain caused by irregular shift work. It consisted of two parts: a survey of
      midwives doing a three-shift work in hospitals (n = 366), and an intervention in
      six maternity wards (n = 45). During the 6-month intervention the influence
      potential of the personnel increased, and the number of quick returns fell. As a
      result, the mental strain of the work decreased and the stress levels fell. The
      positive effects were evident especially among the elderly midwives: their work
      became less strenous and their social interaction improved. Despite the positive
      effects of the intervention, 55% preferred the former system with longer
      continuous free time. The physiological criteria for a good shift system were
      outweighed by the demands of social life, emphasizing the importance of
      individual flexibility and participation in the planning process.

PMID- 8868709
TI  - Marketing analysis of a maternity service by a consumer.
AB  - Marketing analysis is a means of identifying consumer satisfaction, thus
      providing a means of exploiting weaknesses in competitors. As part of a graduate
      midwifery programme a small study was undertaken analysing marketing activities
      used by one competitor provider of maternity care services. The Marketing mix,
      Ansoff matrix and Gap analysis were the marketing tools used. Recommendations to
      midwifery service providers suggest using market research to identify consumer
      expectations and explore areas of both satisfaction and dissatisfaction.

PMID- 8868710
TI  - Three decisions about nurse mentoring.
AB  - The literature of the 1980s and 1990s records enormous interest in mentoring.
      However, this interest is accompanied by anxiety in many professions that the
      role of the mentor is not becoming more clearly defined and has rarely been the
      subject of informative research. This paper reports a research study on the
      mentor role. The study was carried out with 87 nurse mentors and 39 student
      nurses. The nurse mentors and the students agree on the essential core of the
      mentor role. Beyond that, however, the two parties differ in their view. The
      mentors, in addition to the core of the role, emphasize its supportive aspects.
      In contrast, the students predict that, in addition to the core of the role,
      mentors will in future emphasize its challenging aspects. These findings are
      interpreted in the paper, which ends with a logical analysis of the three
      decisions facing nursing managers who respond to the findings reported in the
      paper.

PMID- 8868711
TI  - Pursuing a career in nursing: differences between men and women qualifying as
      registered general nurses.
AB  - Much interest currently focuses on differences in the career intentions and
      career pathways of men and women nurses. This study seeks to add to existing
      knowledge on this subject with findings from a survey of newly qualified
      registered general nurses. Questionnaires were sent to a cohort of 1164 nurses,
      87% of whom responded. Data from the 936 women and 79 men were compared in
      relation to educational and employment background, routes into nursing and career
      intentions at qualification. Procedures for modelling of categorical data were
      applied to these data within the constraints of the study design. Findings showed
      that men were less likely than women to have entered nursing as a first choice
      and less likely to intend working in the community after qualification. Men were
      more likely than women to plan to move out of clinical practice and more likely
      to plan pursuing a postgraduate qualification. Other differences between men and
      women were suggested, but limitations of the study design mean that drawing of
      conclusions had to be more tentative. Consequently, further research on this
      subject is warranted.

PMID- 8868712
TI  - Thinking about tomorrow today: implications for psychiatric mental health
      nursing.

PMID- 8868713
TI  - Challenges and opportunities.

PMID- 8868714
TI  - Responses and needs in a changing situation: staff who work with people with
      learning disability.
AB  - Questionnaires were sent to residential care staff working with people with
      learning disability both in hospital and community settings, to explore any
      changes resulting from implementation of the policy of care in the community.
      Information was obtained on the current job situation of staff, their opinions on
      the effect of the policy of care in the community, their training needs, and
      perceived job prospects for the future. Findings for staff working in a hospital
      setting are compared with those of staff working in the community and discussed
      in the context of changing demands and conditions.

PMID- 8868715
TI  - Behavioural and Instrumental Stressors in Dementia (BISID): refocussing the
      assessment of caregiver need in dementia.
AB  - The importance of supporting family carers of people with dementia is well
      accepted and is likely to remain one of the primary areas of intervention for
      mental health practitioners. This article argues for a holistic assessment of
      need prior to designing intervention strategies. Such an assessment should
      include both objective and subjective stressors. Following discussion of a
      relevant theoretical approach to assessment, a new index for measuring
      behavioural and instrumental stressors is presented.

PMID- 8868716
TI  - An equal struggle (psychodynamic assessment following repeated episodes of
      deliberate self harm).
AB  - Psychodynamic psychotherapy is a complex method of enabling a person to engage
      with life difficulties. This narrative paper investigates the value of
      psychodynamic psychotherapy within the framework of the 'Health of the Nation'
      document (Department of Health 1992). The paper explores an encounter with a
      young gay man who was admitted to the medical unit following an episode of
      deliberate self harm, in response to profound and thematic relationship
      difficulties. The writer (a liaison mental health nurse, working in a general
      hospital setting) examines the complexities of the transference,
      countertransference relationship. A case is made for the facilitation of choice
      as a primary goal of therapy. It is suggested that the inauguration of
      transference resolution is determined through an equitable relationship, in which
      therapist and client are engaged equally in the struggle toward understanding.
      The paper concludes with the suggestion that psychotherapy is an appropriate and
      effective method for dealing with relational conflict. However, personal,
      temporal and social resources may not provide the client with what is, in
      Kleinian terms, a necessary holding environment. The assessment process
      nevertheless can provide important learning and enable significant changes to be
      made in supportive networks.

PMID- 8868717
TI  - Objective burden among primary caregivers of persons with chronic schizophrenia.
AB  - A better understanding of the burden on the family has become increasingly
      important because many families assume a major role in the care of their
      relatives who have schizophrenia. The purpose of this study was to provide
      descriptive information about the negative consequences on the family (e.g.
      physical problems, restrictions in social life, tense relationships in the
      family) reported by the primary caregivers of persons with schizophrenia. Two
      types of objective burden were studied: general and attributable objective
      burden. The former refers to the general consequences on the family while the
      latter corresponds to those consequences specifically attributed to the presence
      of mental illness. Seventy primary caregivers completed a self-report instrument.
      The general negative consequences identified most frequently were tense
      relationships in the household, and the physical and emotional problems of the
      primary caregiver. The most common negative consequences directly related to the
      ill relative were the primary caregiver's emotional problems, the disturbance in
      the primary caregiver's performance of work, and the disruption in the lives of
      other adults in the household. The clinical implications and future directions of
      research are discussed.

PMID- 8868718
TI  - Revisiting the nursing management of the psychopath.
AB  - There has been a growing concern regarding the treatability of those patients
      labelled as psychopathically disordered. Notwithstanding this important debate,
      and the ultimate outcome of it, the nursing management of this categorized legal
      group continues on a daily basis. This paper contributes a theoretical foundation
      to the practicalities of nursing this particularly difficult patient group, based
      upon clinical experience, and offers a nursing perspective to the complexities of
      the debate.

PMID- 8868719
TI  - User involvement in the nursing curriculum: seeking users' views.
AB  - This qualitative study considers the views of users of mental health services on
      a pre-registration nursing curriculum. Semistructured group interviews were used
      to gain the (illustrative) views of twenty members of two user groups on nursing
      knowledge, skills and qualities. Interest in users' views has generally been
      belated or reluctant. In more recent literature, statements emerge about the need
      to develop a climate of respect, acceptance and sensitivity. While nurses have a
      central role in mental health care, a detailed examination from the user's
      perspective has been lacking. Despite the rhetoric of involvement, commentaries
      on nursing practice suggest little has changed. Findings suggest an eclectic
      knowledge base that respects individual differences and the user's experience,
      knowledge of local communities, and better recognition of physical illness is
      required. 'Knowledge of life' is seen as important. An emphasis on interpersonal
      skills is suggested, including flexible responses, information-giving, and
      sensitive handling of tense situations. This should be balanced against
      'practical' nursing. Traditional teaching in relation to 'psychotic' experiences
      is challenged. It is suggested that caring should be emphasized as much as
      'rational knowledge'. Developing responsive qualities that minimize 'distancing'
      may demand a reevaluation of boundaries between user and professional.

PMID- 8868720
TI  - Coping skills in mental health nursing: do they make a difference?

PMID- 8868721
TI  - The effect of a psychiatric secondment on Hong Kong chinese student nurses'
      attitudes to mental illness.

PMID- 8868722
TI  - Dealing with conflicting reviewers' comments.
AB  - Most nursing journals use two or three reviewers to help the editor decide on
      acceptance or rejection. Although this helps give the editor a wide range of
      perspectives for making the acceptance decision, it sometimes results in
      confusion if reviewers' comments conflict rather than compliment each other. This
      article describes strategies reviewers can use to prevent this problem and
      editors and authors can use to deal with the conflicts when they occur.

PMID- 8868723
TI  - Converting a presentation to a manuscript.
AB  - Presenting and publishing are closely linked. Although many authors are later
      asked to speak, the reverse is also true. Many presenters are asked to author
      manuscripts based on their presentations. This author who is experienced in
      professional presentations and editing gives tips to nurse authors on how to
      develop a manuscript from a presentation.

PMID- 8868724
TI  - Stories from the field.

PMID- 8868725
TI  - Of ethics committees, protocols, and behaving ethically in the field: a case
      study of research with elderly residents in a nursing home.
AB  - In this paper we discuss differing discourses of research ethics committees and
      the clinical research field. Reflections on our experience of conducting research
      in a nursing home are used to highlight the tensions and inconsistencies that
      arise from these discourses and the need to behave ethically in the field. While
      accepting the need for adherence to guiding principles of duty based ethics, we
      have found that practical moral decisions in the field required that, as
      individual researchers, we needed to exercise discretionary judgement, informed
      by the ethic of care and the concern for the well-being of research participants.

PMID- 8868726
TI  - Vietnam memories: Australian army nurses, the Vietnam war, and oral history.
AB  - This paper is about women nurse veterans from the Royal Australian Army Nursing
      Corps (RAANC) who served in Vietnam. I aim to develop an understanding about
      these nurses that might place their experiences into a wider context. My
      conclusions provide starting points for future studies on myth, remembering and
      oral history.

PMID- 8868727
TI  - (Re) writing ethnography: the unsettling questions for nursing research raised by
      post-structural approaches to 'the field'.
AB  - Positivist ethnographic research situates the participant observer in an
      objectivist position towards the field. Using post-structural perspectives to
      analyse the field challenges and unsettles objectivist assumptions underpinning
      ethnography. Neither is merging of the two approaches completely unproblematic. A
      crucial element in a coherent amalgam centres around resolution of potential
      contradictions emanating from the place of field notes in ethnographic research,
      and the position of the researcher (author) vis-a-vis such notes. Contemporary
      approaches to field notes maintain that such notes are not an objective
      description of the field, unaffected by the voice of the researcher. Rather,
      observational records are to be regarded as text, with characteristics in common
      with all texts. The ethnographic record is constituted as much by the
      positionality of the researcher as by the research participants. The nurse
      researcher can be viewed as participant in the constitution of the field. In
      unsettling and challenging taken-for-granted understandings about nursing
      practice, I am affirming the centrality of the position of the nurse in nursing
      research.

PMID- 8868728
TI  - The nurse researcher: an added dimension to qualitative research methodology.
AB  - Nurse researchers are increasingly adopting qualitative methodologies for
      research practice and theory development. These approaches to research are, in
      many cases, more appropriate for the field of nursing inquiry than the previously
      dominant techno-rational methods. However, there remains the issue of adapting
      methodologies developed in other academic disciplines to the nursing research
      context. This paper draws upon my own experience with interpretive research to
      raise questions about the issue of nursing research within a social science
      research framework. The paper argues that by integrating the characteristics of
      nursing practice with the characteristics of research practice, the researcher
      can develop a 'nursing lens', an approach to qualitative research that brings an
      added dimension to social science methodologies in the nursing research context.
      Attention is drawn to the unique nature of the nurse-patient relationship, and
      the ways in which this aspect of nursing practice can enhance nursing research.
      Examples are given from interview transcripts to support this position.

PMID- 8868729
TI  - Typists' influences on transcription: aspects of feminist nursing epistemic
      rigour.
AB  - This paper describes the process by which female typists became participants of
      sorts while transcribing audiotaped interviews. The primary data included
      sensitive and sexual subject matter about women's Pap smear (PS) experiences.
      Besides overcoming minor technical difficulties, the major discovery was that the
      typists had a tendency to interpolate and even normalize the data. A feminist
      post-structuralist perspective was extended to examine these interpolations as
      secondary data. This revealed that the typists were becoming unexpected
      participants as commentators, validators, analysts and normalizers of the data.
      From the subjective positions of both medical typists and recipients of PS, the
      typists provided data validation that included contradictions and transgressions
      from the cancer screening scheme propaganda. Furthermore, both typists were
      exposed to other women's PS stories and experienced vicarious consciousness
      raising. For one typist this included embodiment of other women's distress,
      raising questions about the occupational hazards associated with transcribing
      distressing data. Thus the social and relational aspects of those involved in the
      transcription process proved influential to both the data (and analysis), and to
      the practical aspects of data management. I argue that details of such influences
      need to be submitted for scrutiny as additional aspects of rigour.

PMID- 8868730
TI  - Nursing research reframed by the inescapable reality of practice: a personal
      encounter.
AB  - This paper describes how an innocent venture outside the confines of academia to
      update my nursing skills completely changed the focus of my research. I was
      deeply involved in the theoretical development of my thesis, which I thought was
      a feminist exploration of the meaning of health for mid-life women. I was
      immersed in feminist theory and was exploring the work of the French Feminists. I
      had written comprehensive draft chapters about nursing, women's bodies and
      science. While I was absorbed in my theoretical exploration I decided to venture
      back into practice to improve my nursing skills. I am still unsure why I chose to
      do this; however, in hindsight, my theoretical exploration was inexorably pushing
      me in that direction. While my conscious thinking was focused on my stated topic,
      my subconscious (my intuition) turned me towards another. Being confronted with
      the reality of nursing practice through working with staff nurses in a
      gynaecological ward caused a major disjunction in every aspect of my research:
      the topic, my methodology and the setting, and the experience challenged my
      feelings about nurses and nursing. This inevitably led to a dramatic and
      fundamental change in my research.

PMID- 8868731
TI  - Unfinished business: interviewing family members of critically ill patients.
AB  - This 'story from the field' emerges from qualitative research conducted with
      relatives of patients admitted to intensive care. A disturbing feature of
      researching the needs of family members of critically ill patients is the intense
      emotion that is often generated during the course of interviewing. For some the
      opportunity to talk about the experience of having a loved one in an intensive
      care unit was therapeutic; for others it meant anguish and despair as they
      relived the event that resulted in a life-threatening illness. Despite being a
      reasonably experienced educator and critical care nurse, I was unprepared for the
      intensity of feelings shown by many of the participants. I found that exposure to
      this kind of suffering was emotionally draining, experiencing the various roles
      of confidante, nurse, counsellor and researcher. It became important to share my
      thoughts and feelings and unwind with an independent friend and colleague as a
      way of debriefing. Methodological and ethical issues that arose included:
      generating a situation that potentially required therapeutic intervention; the
      impact on the 'purity' of data of becoming emotionally enmeshed; and the level of
      investigator preparedness when researching sensitive topics. The issue of walking
      away from an intensely emotional and intimate interview often leaves one with a
      sense of 'unfinished business'.

PMID- 8868732
TI  - An exploratory, descriptive study of community attitudes towards people with
      mental illnesses in a British community.

PMID- 8868733
TI  - Narrative picturing: ushering experiential recall.

PMID- 8868734
TI  - Continuing care: policies and implications.

PMID- 8868735
TI  - Evaluating care services for people living with dementia.

PMID- 8868736
TI  - Measuring outcomes of care in a day hospital setting.

PMID- 8868737
TI  - Health care at the sharp end.

PMID- 8868739
TI  - Stepping into business.

PMID- 8868738
TI  - Robbed with impunity.

PMID- 8868740
TI  - Great friends together.

PMID- 8868741
TI  - What price community care?

PMID- 8868742
TI  - Ethics in action. A woman is admitted to the ED after being raped.

PMID- 8868744
TI  - EKG electrode placement. A refresher course.

PMID- 8868743
TI  - Grieving families need your help.

PMID- 8868745
TI  - Salvaging blood from the chest.

PMID- 8868746
TI  - A new survey. Workload, UAPs, and you.

PMID- 8868747
TI  - Ulcer therapy update.

PMID- 8868748
TI  - These nurses take flight.

PMID- 8868749
TI  - You don't have to care for every patient.

PMID- 8868751
TI  - Judge not.

PMID- 8868750
TI  - OTC products help smokers quit.

PMID- 8868752
TI  - Pressure sore prevention in a rehabilitation setting: implementing a programmatic
      approach.
AB  - The prevalence of pressure sores and the number of patients at risk for
      developing pressure sores in the rehabilitation setting support the need for
      designated resources and interventions for both prevention and management.
      Today's healthcare environment, with increasing patient acuity and decreasing
      length of stays, requires nurses to have strategies for delivering and
      documenting care without increasing workload. This article describes an approach
      that directs nursing activities, incorporates aspects of the Agency for Health
      Care Policy and Research clinical practice guidelines, and links care processes
      and outcomes with documentation.

PMID- 8868753
TI  - Nursing management of pressure ulcers using a hydrogel dressing protocol: four
      case studies.
AB  - People with spinal cord injury (SCI) are at risk for developing pressure ulcers
      throughout their lives. Pressure ulcers can lead to significant morbidity,
      prolonged hospitalization, and diminished quality of life. Rehabilitation nurses
      play a vital role in preventing and treating pressure ulcers in these clients. In
      this article, the authors describe four case studies of clients with SCI who have
      pressure ulcers and discuss the implementation and outcome of a nursing
      management protocol based on the use of hydrogel dressings. These dressings have
      been found to promote wound healing, protect against contamination and infection,
      and reduce pain. They also are usually acceptable to the client and are cost
      effective. Hydrogel dressings should be considered as one component of an
      individualized plan of care for the development of pressure ulcers.

PMID- 8868754
TI  - Halo skeletal traction pin site care: toward developing a standard of care.
AB  - Halo skeletal traction may be used to immobilize a patient's head and neck
      following a cervical fracture. Prevention of infectious reactions around the pin
      sites of halo traction is a priority in rehabilitation nursing practice. Although
      prophylactic treatment of skeletal pin sites is a generally accepted practice,
      there is great diversity of opinion and very limited systematic investigation as
      to how the sites should be treated. In this article, the author reviews the
      literature on pin site care and suggests a protocol based on the current
      literature.

PMID- 8868755
TI  - Caring for the caregivers: the hidden victims of illness and disability.
AB  - As advances in medical care extend the life expectancy of the elderly as well as
      those with disabling and chronic conditions, new sets of problems often emerge.
      One such problem is the constantly growing population of those providing care for
      spouses who, due to a disability, chronic illness, medical condition, or simply
      the frailty of old age, can no longer totally care for themselves. Well spouses
      who provide care are at risk for numerous physical, mental, emotional, social,
      and financial problems of their own. The literature points to several issues that
      emerge from the caregiving experience, as well as appropriate and effective
      responses to these issues. Nurses are in a position to identify at-risk
      caregivers and to advise them of their increased risk of physical and emotional
      problems. Addressing caregivers' needs helps to ensure that better care will be
      given to those dealing with or recovering from chronic illness, disability, or
      medical condition and, thus, that there will be improved results.

PMID- 8868756
TI  - A self-management program for chronic obstructive pulmonary disease: relationship
      to dyspnea and self-efficacy.
AB  - The purpose of this quasi-experimental study was to determine the effects of a
      nurse-directed self-management program on dyspnea and self-efficacy levels in
      patients with chronic obstructive pulmonary disease (COPD). The Health Belief
      Model and the Theory of Self-Efficacy provided the theoretical framework for the
      study. The sample included 10 COPD patients from rural North Carolina who
      attended a 6-week nurse-directed self-management program. Dyspnea and self
      efficacy were measured before and after the program by using a vertical visual
      analogue scale for dyspnea and the COPD Self-Efficacy Scale. A single-group quasi
      experimental design that incorporated a pretest and a posttest was used. Paired t
      tests were used to compare the pretest and the posttest levels of dyspnea and
      self-efficacy. The findings revealed no significant change in levels of dyspnea
      after the program. Levels of self-efficacy, however, were found to have increased
      at a statistically significant level (p < .001) following the program. This study
      indicates that using a group teaching method to teach self-management skills
      improved self-efficacy levels.

PMID- 8868757
TI  - Psychosocial issues following serious head injury: a case study of an adolescent
      girl.
AB  - This article is a case study of an adolescent girl who sustained a serious head
      injury following an attack by strangers. The head injury caused an epidural
      hemorrhage that exerted pressure on her brain stem and resulted in spastic
      quadriplegia. In this case, the major issues in rehabilitation were the patient's
      ability to learn to communicate and normalize and gain control over various
      aspects of her life. Because of the lack of a specialized rehabilitation setting
      for children and adolescents, rehabilitation took place in an acute care setting,
      which makes this story unusual in many ways. Staff issues were significant
      because of the nurses' inexperience with rehabilitation issues and because of the
      setting. This article describes the primary nurse's experience with this patient
      over several months. During this phase of rehabilitation, psychosocial issues
      were a major concern. Fifteen months after rehabilitation began, the patient
      moved back home and returned to high school. She communicates by using a computer
      and by using her eyes, and she uses a wheelchair. Despite everything, she is
      determined to get better and to prepare herself for the future.

PMID- 8868759
TI  - Save our skin (SOS).

PMID- 8868758
TI  - Using self-efficacy theory to educate patients with chronic obstructive pulmonary
      disease.
AB  - The predominant debilitating symptom in patients with chronic obstructive
      pulmonary disease (COPD) is shortness of breath. Self-efficacy theory has been
      used in a case study approach to begin examining the expectations of a patient
      with COPD who attended a pulmonary education program. Mr. M. was selected for the
      case study because his condition typifies many of the problems encountered by
      patients with COPD. Mr. M.'s self-confidence in managing his breathing difficulty
      was measured by using the COPD Self-Efficacy Scale (CSES) before an educational
      program began and again 1 month and 6 months after the program. The CSES measures
      patients' confidence in their ability to manage or avoid breathing difficulty in
      a variety of situations. Mr. M.'s scores on the CSES improved in most areas.
      Incorporating programs to increase patients' self-efficacy may have implications
      for rehabilitation nurses who help patients with COPD manage their breathing
      difficulty.

PMID- 8868760
TI  - I had heard all I wanted to know about bed 1 in room 11!

PMID- 8868761
TI  - An ill wind. Interview by Colin Wright.

PMID- 8868763
TI  - Thoughts after birth.

PMID- 8868762
TI  - Daylight robbery.

PMID- 8868764
TI  - Ethics. Samantha's wish.

PMID- 8868766
TI  - Ethics. Did the NHS fail child B?

PMID- 8868765
TI  - Ethics. Body language.

PMID- 8868767
TI  - A plan for action to reduce hospital-acquired infection.
AB  - Surveillance is recognised as an essential component of the prevention and
      control of infection in hospitals. The second National Prevalence Survey in 1993
      94 showed a mean hospital-acquired infection prevalence rate of 9%. The
      Nosocomial Infection National Surveillance Scheme is being developed in England
      to measure the incidence of nosocomial infection; similar schemes are being
      developed elsewhere in the UK. Surveillance aims to reduce the risk of nosocomial
      infection by highlighting areas where changes need to be made, measuring the
      effects of change and leading to the development of guidelines for good practice.

PMID- 8868768
TI  - Making sense of cancer chemotherapy.
AB  - Chemotherapy is a principal form of treatment for cancer. This paper introduces
      the principles of this method of treatment showing how chemotherapeutic drugs
      disrupt cell division and inhibit tumour growth. The main groups of drugs are
      discussed and their mechanism of action is described.

PMID- 8868769
TI  - Learning to approach patients' sexuality as part of holistic care.
AB  - Assessing a patient holistically means assessing him or her with regard to all
      aspects of his or her personality. As sexuality is an intricate part of
      everyone's personality, it should be taken into account in comprehensive nursing
      care. If nurses are to approach the issue of patients' sexuality and how their
      illness may affect it, they must first be sure they feel confident and
      knowledgeable to do so. This paper looks at how carers can explore their own
      beliefs and inhibitions regarding sexuality.

PMID- 8868770
TI  - Clinical evaluation: analysing and discussing the results.
AB  - This is the last of six papers considering the evaluation of clinical treatments.
      The purpose of clinical evaluation is to identify changes that result from a
      particular form of treatment. Study findings are presented in the results section
      of a report. They may be summarised in tables or graphs so that changes, and the
      extent of those changes, can be clearly identified. Statistical tests may be used
      to confirm that these changes are due to treatment and not to chance. The choice
      of statistical tests employed depends on the methods used and should be selected
      when designing the study. The meaning of the results and their implications are
      discussed in the final section of of this paper.

PMID- 8868771
TI  - How the Burford reflective model boosts care standards.
AB  - Reflective practice is grounded in the practitioner's everyday experiences. This
      is why this second part of an examination of reflective models of nursing
      considers the experiences of two nurses who used the Burford reflective model to
      inform and refine the care they offer. One reflects on a routine series of
      community visits, the other focuses on the drama and distress surrounding a
      terminal illness.

PMID- 8868772
TI  - Elderly counts. A nice place to grow old?

PMID- 8868773
TI  - Part-time working: speaking out.

PMID- 8868774
TI  - Complementary medicine: more than skin deep.

PMID- 8868775
TI  - Invidious web.

PMID- 8868776
TI  - Health care lottery.

PMID- 8868777
TI  - Personal finance. Planning a pay-off.

PMID- 8868778
TI  - Infection control. Not quite good enough to eat.

PMID- 8868779
TI  - Infection control. Hygienic practices.

PMID- 8868780
TI  - Professional development. Care planning: knowledge for practice (continuing
      education credit).

PMID- 8868781
TI  - What is the specialty of orthopaedic nursing?

PMID- 8868782
TI  - Outpatient ACL surgery: the role of the home health nurse.
AB  - Outpatient ACL reconstructive surgery is a recent trend in orthopaedics. The
      Visiting Nurse Association (VNA), a large home care agency in Northern Virginia,
      provides skilled rehabilitation nursing care to these patients during the
      immediate postoperative period. Home care nurses visit these patients upon
      discharge from the hospital on the day of surgery and revisit on the first
      postoperative day. The nurses administer injections for pain, assess and
      reinforce dressings, evaluate the operative extremity for circulatory and sensory
      changes and instruct the clients regarding postoperative protocols. Patients who
      have received home health nursing following ACL reconstruction have recovered
      successfully without rehospitalization.

PMID- 8868783
TI  - Same-day surgery: the nurse's role.
AB  - Outpatient surgery is one of the fastest growing trends In health care today.
      Providing preoperative and postoperative care to a diverse patient population in
      a limited amount of time presents numerous challenges. The nursing staff is
      required to assess the patient and resources, plan for the scheduled surgery and
      postdischarge care, implement the plan, and evaluate the patient's and family's
      understanding of the information and their ability to provide for self-care at
      home in as little as 2 hours. Preoperative care is discussed in this article
      along with specific guidelines for postoperative recovery and discharge planning.
      Care of the orthopaedic patient is highlighted throughout the discussion.

PMID- 8868785
TI  - Wagon wheel fracture. Bumper fracture.

PMID- 8868784
TI  - Nursing care of the patient with metastatic bone disease.
AB  - The incidence of metastatic bone disease is great. Half of the million cancers
      diagnosed yearly spread to bone. The nursing management of the patient involves
      assessment and psychologic support during the diagnosis. Patient education for
      prophylactic or stabilization surgery, radiation, hypercalcemia, and other
      treatments is given. Ongoing assessment of pain relief as well as the patient's
      mobility makes nursing care complex.

PMID- 8868786
TI  - Issues at the end of life.
AB  - A recent study by David Asch reported in the New England Journal of Medicine has
      intensified discussions about euthanasia and assisted suicide. That investigation
      has prompted nurses and other health care providers to raise questions about what
      is appropriate care for dying patients. To that end, this article provides an
      overview of relevant issues for nurses to consider when patients are at the end
      of life: quality of life, suffering, pain management, double effect, respect for
      autonomy, and trust and nonabandonment. Understanding these issues and enhancing
      communication between and among all relevant individuals when treatment decisions
      are being made will enable nurses to provide appropriate patient care at the end
      of life.

PMID- 8868787
TI  - The new nursing leader for the new world order of health care.

PMID- 8868788
TI  - Assessing the accuracy of femoral component placement in custom cemented hip
      replacement.
AB  - Leg length disparity is a frequent complication of hip arthroplasty. The most
      common problem is lengthening of the operative leg, which usually occurs on the
      femoral side. The Belfast Hip Group has designed a femoral caliper that offers an
      effective solution to the problem. This instrument is accurate and easy to use
      and could be applied by the orthopaedic surgeon to control leg length. Patients'
      perception of the success of their total hip replacement is influenced by their
      ability to walk without appliances or pain. With minimal additional effort and
      planning, this caliper will ensure greater control of leg length measurement in
      total hip replacement patients.

PMID- 8868789
TI  - Vitamin E: hype or hope.
AB  - Unlike other vitamins, Vitamin E probably has received less attention in the past
      because humans are not likely to suffer from deficiency disorders. This fat
      soluble vitamin is available in many foods, is easily stored, and is readily
      reused by the body. The original research carried out in the 1920s found that a
      Vitamin E deficiency in rats produced problems in their reproductive capacity.
      The name given to the substance at that time, "tocopherol," reflects this action
      as it is taken from the Greek word, "tocos," meaning "to give birth."

PMID- 8868790
TI  - Multimedia in nursing and patient education.
AB  - Multimedia education or computer-based instruction is currently being used in
      both patient and nursing education for staff development, continuing education,
      general health information, and informed consent. It can be used to teach
      content, skills, and concepts, as well as to simulate situations. Multimedia may
      be incorporated as a part of other hospital systems to provide individualized
      patient education by using actual patient data. Multimedia as an instructional
      strategy has some definite advantages and disadvantages that can affect
      integration and use. It will be used more and more in the health care environment
      to provide consistent, accurate information to nurses and patients.

PMID- 8868791
TI  - You make the diagnosis: case study--the family as client in the school setting.

PMID- 8868792
TI  - Writing for publication.

PMID- 8868793
TI  - Considerations in diagnosing in the spiritual domain.
AB  - As nurses move into the spiritual domain, it is important to recognize beliefs
      and values implicit in Western Judeo-Christian culture. Cross-cultural
      comparisons are used to illuminate three Western spiritual assumptions:
      monotheism, transcendence, and dualism. Awareness of these assumptions can help
      nurses accommodate spiritual-cultural pluralism. Relevant to Western cultural
      bias, three types of errors lead to misdiagnosing spiritual distress or spiritual
      growth by confusing ideas of religion, psychology, and medicine with
      spirituality. These errors are discussed relevant to nursing practice. More work
      needs to be done to differentiate and understand spiritual issues related to
      health.

PMID- 8868794
TI  - The congruence of nursing diagnoses and supporting clinical evidence.
AB  - In this secondary analysis, 890 patients 40 years of age and older were assessed
      within 24 hours of transfer from intensive care to medical/surgical units.
      Nursing diagnoses documented in the hospital record were compared to supporting
      clinical evidence obtained from subjects, the hospital record, and interviews
      with subjects and nurse caregivers. The congruence, based on the kappa statistic,
      between the nursing diagnosis and clinical evidence ranged from 0.1% for altered
      thought processes to 10% for impaired gas exchange, impaired physical mobility,
      and potential for injury, while no diagnoses were made for self-care deficits or
      sensory alterations, visual, when clinical evidence for them was available.

PMID- 8868795
TI  - A multivariate approach for validation of anxiety and fear.
AB  - The purpose of this study was to reduce the defining characteristics for the
      nursing diagnoses anxiety and fear into sets of smaller, more manageable and
      meaningful variables for clinical use and further investigation. A sample of 233
      nurse experts rated defining characteristics of anxiety and fear on three study
      instruments; a sample of 69 hospitalized clients rated defining characteristics
      of anxiety on one study instrument. Results of principle components analyses
      identified patterns within defining characteristics and provided consolidation of
      characteristics into meaningful and usable sets.

PMID- 8868796
TI  - Uncircling the wagons.

PMID- 8868797
TI  - Debbie LaBerge: caring for Amish and Mennonite families. Interview by Karan
      McGinn.

PMID- 8868798
TI  - Overview of the legal issues pertaining to the treatment of infertility.

PMID- 8868799
TI  - Images of infertility.
AB  - A key purpose of this article is to focus on the major role of the nurse
      practitioner in providing the necessary support to couples as they cope with
      infertility and its many manifestations. The connection between the losses and
      stresses of infertility and its treatment, the emotional reactions, and the
      appropriate interventions are discussed and visually presented in this paper.

PMID- 8868800
TI  - Recurrent pregnancy loss: a review.
AB  - Recurrent pregnancy loss (RPL) is a frustrating problem for both the patient and
      the clinician. The causes of RPL are diverse and may be associated with genetic,
      anatomic, microbiologic, endocrine, or immunologic factors. When a couple is
      ready for an evaluation, the nurse practitioner needs to be able to discuss
      possible causes, aspects of diagnostic testing, and available options.
      Reassurance and clear information about prognosis are important and emotional
      support must be offered throughout the investigation and subsequent pregnancy.

PMID- 8868801
TI  - The infertile couple: an overview of pathophysiology and diagnostic evaluation
      for the primary care clinician.
AB  - Current incidence of infertility is discussed, followed by an outline of both
      endocrine and anatomic causes of male and female infertility. A comprehensive,
      yet "low tech", approach to the infertility evaluation by the primary care
      clinician is presented. Nursing implications are discussed, towards a goal of
      minimizing the couple's anxiety over the often complicated, confusing--and
      expensive--choices involved in infertility diagnosis and treatment.

PMID- 8868802
TI  - Forty years of infertility management--exponential progress and a demanding
      future.

PMID- 8868803
TI  - In-hospital evaluation of 7.5% hydrogen peroxide as a disinfectant for flexible
      endoscopes.
AB  - The effectiveness of Sporox (Reckitt and Colman Inc, New Jersey), a 7.5% solution
      of hydrogen peroxide, was compared with that of Cidex (Johnson & Johnson), a 2%
      solution of alkaline glutaraldehyde, in the manual disinfection of flexible
      endoscopes at a large general hospital. For disinfection with Sporox, a soaking
      time of 10 mins at room temperature was used. The same disinfectant bath was used
      for nearly seven weeks and the Sporox level was monitored using reagent strips
      supplied with the product. Controls included endoscopes with precleaning (enzyme
      detergent) but without any disinfection, and endoscopes that were precleaned and
      disinfected in Cidex only. A total of 3 mL of sterile normal saline was used for
      sampling each channel and immediately plated to detect aerobic and anaerobic
      bacteria as well as mycobacteria. There were 76 endoscopes sampled. Of these, 55
      were disinfected in Sporox, 13 were disinfected in Cidex and eight were
      precleaned but not disinfected. None of the samples from endoscopes disinfected
      with either Sporox or Cidex yielded isolates generally regarded as pathogenic for
      humans. The findings of this in-hospital study indicate that Sporox is at least
      as efficacious as Cidex in the disinfection of flexible endoscopes between
      patients. In addition, the exposure time to Sporox was half as long compared with
      Cidex, and hydrogen peroxide is much less toxic to humans and the environment.
      Therefore, Sporox appears to have considerable potential as a safer substitute
      for glutaradehyde-based products in the decontamination of flexible endoscopes.

PMID- 8868804
TI  - International Federation of Infection Control (IFIC): brief report.

PMID- 8868805
TI  - Health system development and infection control in Russia.

PMID- 8868806
TI  - Treatment of purulent wounds in controlled abacterial space.

PMID- 8868807
TI  - Infection prevention update.

PMID- 8868809
TI  - Unit profile: Central Coast Area Health Service--Gosford Hospital intensive care
      unit.

PMID- 8868808
TI  - Radiofrequency ablation: a review of its application and nursing considerations.
AB  - Radiofrequency ablation (RFA), a therapeutic electrophysiological procedure, has
      become the treatment of choice for a number of cardiac arrhythmias. These
      arrhythmias include those of anomalous pathways, as seen in AV nodal re-entry
      tachycardia and Wolff-Parkinson-White syndrome, and re-entry tachycardias of
      atrial and ventricular origins. This paper discusses the mechanism of RFA and the
      physiology of re-entry circuits, and outlines the cardiac arrhythmias treated by
      RFA. The nursing responsibilities associated with the RFA procedure--including
      patient education, observation for potential complications, and other peri- and
      post-procedure considerations--are then addressed.

PMID- 8868810
TI  - Critical care graduate diploma: nursing students' needs identified in evaluation.
AB  - In 1993 a Graduate Diploma in Critical Care Nursing was developed by the Faculty
      of Nursing and Health Sciences Griffith University--Gold Coast Campus, in
      collaboration with hospitals in the South Coast and Brisbane regions of
      Queensland and the Queensland Nurses Union of Employees. An independent
      evaluation of this 1-year full-time course identified several issues which should
      be considered when planning courses of this type. Student characteristics varied,
      and most gained entry into this course on the basis of prior experience. Many
      students lacked such 'hardware' skills as library access, computing and study
      ability. By the end of the course, students perceived that their prospects for
      career advancement were enhanced by the knowledge and skills gained from the
      course and that they had demonstrated professional development. Students
      emphasised the need for a strong focus on the clinical component of the course.
      Planning for specialty education should include comprehensive induction programs
      which provide opportunities to develop 'hardware' skills, and special attention
      must be paid to the clinical components.

PMID- 8868812
TI  - Directions for critical care nursing: where are we going from here?

PMID- 8868811
TI  - Conference report: the International Conference on Continuous Renal Replacement
      Therapies: San Diego, California--November 8-10, 1995.

PMID- 8868813
TI  - The future of Australian postgraduate critical care nursing education.

PMID- 8868814
TI  - A position statement on resuscitation by all levels of nurse. Confederation of
      Australian Critical Care Nurses Inc.
AB  - As part of its brief, the CACCN Inc. Advanced Life Support (ALS) Subcommittee has
      been reviewing and compiling a national policy for education in ALS for nurses.
      We believe this is an appropriate pursuit, since critical care nurses are at the
      forefront of practice in this area and also care for patients receiving life
      saving interventions. One of the Subcommittee's concerns is the lack of a uniform
      approach to the issue of resuscitation across the nursing community, despite the
      broad applicability of such skills to many of the diverse settings in which
      nurses practice. The following is a position statement aimed at setting a
      precedent for both Basic and Advanced Life Support practice and education in the
      Australian nursing context. We have distributed the statement widely to stimulate
      debate and, eventually, a broader acceptance of this competency for nurses. We
      look forward to your comments.

PMID- 8868815
TI  - From abstract to acclaim.
AB  - Increasing specialisation in the health-care sector requires nurses to be
      proficient communicators both within their own profession and among other health
      care disciplines. Although the work environment provides numerous opportunities
      for oral communication, traditionally we have been taught written communication.
      Like scientific writing, an oral presentation demands a sense of planning,
      audience awareness and attention to detail. Yet, because of the different medium,
      other important factors must also be considered. While a reader may select
      passages or reread a report, the audience must listen in a linear way. Your voice
      and body, aided by visual displays, will have a different effect on the listener
      than the printed pages have on the reader. Therefore, it is important to
      concentrate on both the content and the method of presentation if the audience is
      to be left feeling inspired. This article outlines the planning of a
      presentation, development of visual aids and delivery of a polished performance.

PMID- 8868817
TI  - Interview: the Hon. Dr Michael Wooldridge MP, federal minister for health.
      Interview by Ged Williams.

PMID- 8868816
TI  - Casemix update: australian critical care costs and service weights: part 2.
AB  - In Part 1 of this report (Australian Critical Care 8(4):10-12) the background,
      methods and main results of the National Critical Care Service Weights Study were
      presented. The purpose of this part of the report is to present the costs and
      corresponding service weights for some of the common and high-cost DRGs
      (diagnosis related groups) seen in each type of unit. Finally, the implications
      of the results and the limitations of the study will be discussed. The national
      study included 20 public hospital adult intensive care units (ICUs), eight
      private hospital adult ICUs, five coronary care units, four paediatric ICUs and
      seven neonatal ICUs. The units which contributed patient data to the study were
      randomly selected from units across the country and agreed to participate in the
      study. Some randomly selected units declined to participate in the study.

PMID- 8868818
TI  - Beyond 2000--leading Australian critical care nursing into the future. Strategic
      planning for CACCN Inc.--1996.

PMID- 8868819
TI  - The emergence of competency standards for specialist critical care nurses.

PMID- 8868820
TI  - Sleep, epilepsy and antiepileptic medications: nursing strategies to improve
      sleep quality.

PMID- 8868823
TI  - PREP: who benefits?

PMID- 8868821
TI  - Anticipatory management of status epilepticus.

PMID- 8868822
TI  - Uninsurable risks in care.

PMID- 8868824
TI  - A determined approach.

PMID- 8868825
TI  - Dopamine at work.

PMID- 8868826
TI  - Choices in care.

PMID- 8868827
TI  - Partnerships in care.

PMID- 8868828
TI  - A flexible approach.

PMID- 8868829
TI  - Acknowledging loss.

PMID- 8868831
TI  - Feedback on care.

PMID- 8868830
TI  - Cynics may conclude.

PMID- 8868832
TI  - Highs and lows of independent living.

PMID- 8868833
TI  - Falling through the net.

PMID- 8868834
TI  - Be a champion: children/adolescents and HIV/AIDS.

PMID- 8868835
TI  - A school-based mental health clinic for adolescent mothers.
AB  - TOPIC: The Department of Mental Health Nursing at Oregon Health Sciences
      University mental health program at an alternative high school for teenage
      mothers and their children. PURPOSE: To provide direct mental health services to
      approximately 50% of the student population. Mental health concerns apparent with
      this population of young mothers and their children include issues of violence
      and abuse, depression, developmental delay, and conduct disorder. This paper
      describes the successes and failures of this mental health program in hopes of
      helping other schools of nursing establish similar school-based mental health
      programs in their communities. CONCLUSIONS: Teenage mothers need a safe haven
      where they can experience trust and acceptance. In the therapeutic atmosphere of
      this school-based program, young women were able to explore their feelings
      regarding past violence, learned to nurture their children, and gained an
      increased sense of self-efficacy.

PMID- 8868836
TI  - Case studies of children presenting with a history of ritualistic abuse.
AB  - TOPIC: Ritualistic child abuse is an alarming and controversial problem. Child
      psychiatric nurses need to increase their awareness of the clinical picture
      associated with this specific form of abuse. PURPOSE: This article reviews the
      literature to date on ritualistic child abuse and addresses the controversy
      surrounding the phenomena. SOURCES: A small research project using historical
      data collection methods reviewed hospital records of children with a documented
      history of ritualistic abuse. Results are organized into clusters of linked
      interrelated characteristics. CONCLUSION: The symptom characteristics of these
      children revealed medical/somatic symptoms, distortion of self-oncept and world
      view, and a variety of emotional disturbances. The findings of this study are
      presented with implications for nurses who care for clients with a history of
      ritualistic abuse.

PMID- 8868837
TI  - Reducing violence in a child psychiatric hospital through planned organizational
      change.
AB  - TOPIC: A successful attempt to reduce aggressive behaviors and counter aggressive
      staff interventions, including seclusion and restraint, in a child psychiatric
      hospital. PURPOSE: To offer a model for reducing violence within child
      psychiatric facilities. SOURCES: The agency in which this project was carried out
      was a 50-place public child psychiatric hospital affiliated with an urban
      university. Discussion includes the strategies utilized including utilization of
      practice-based research, assessment of the level of aggression within the agency,
      change in staff perception about the use of coercive interventions to manage
      behavior, revision of the behavior management program and of policies relating to
      crisis events, and increased involvement of families. CONCLUSIONS: This
      experience in reducing aggression within the hospital validates theory that
      suggests that violence within institutions is context-based, involving patients,
      staff, and the institutional climate. The authors believe that the outcomes
      support the proposition that the use of coercion is determined more by traditions
      of practice and the mindset of the staff than by clinical necessity, and that its
      use can be significantly reduced by organization interventions.

PMID- 8868838
TI  - Nonstimulant medications in the treatment of attention deficit hyperactivity
      disorder.

PMID- 8868839
TI  - Who will speak and who will act?

PMID- 8868840
TI  - The silent victims of domestic violence--who will speak?
AB  - TOPIC: Children who witness domestic violence are themselves victims of abuse.
      Unless directly abused, they are often overlooked and do not receive adequate
      services. PURPOSE: The authors contend that helping professionals as well as the
      state must attend to the ethical principles of beneficence, autonomy, and justice
      in dealing with these children. Children, who witness violence at home, must
      receive top priority in the allocation of scarce resources. SOURCES: Published
      literature, clinical experience. CONCLUSION: Diagnostic screening and assessment
      efforts must incorporate standard questions about family violence into all mental
      health and school counseling interviews. Sensitive intervention and referral,
      linking victims and witnesses with intervention specialists, will do much to
      limit the sequelae often seen with family violence. Nurses must advocate for and
      support primary prevention programs in elementary and secondary school systems.

PMID- 8868841
TI  - Researching sensitive issues in child psychiatric nursing: ethical concerns.
AB  - TOPIC: Research in the field of child psychiatric nursing is greatly needed. The
      sensitive nature of many potential topics has hindered research in the field.
      PURPOSE: This paper defines sensitive research and explores the ethical issues
      encountered when designing studies on sensitive issues for the purpose of
      increasing awareness of the problems involved. SOURCES: A synthesis of the
      nursing, psychiatric, psychological, and sociological literature resulted in
      identification of potential ethical problems, as well as suggestions for managing
      these ethical issues. CONCLUSION: Well-designed research on sensitive issues that
      meets the ethical principles of beneficence, respect, and justice will contribute
      to the knowledge base of child psychiatric nursing.

PMID- 8868842
TI  - Behavioral treatment of children with autism, mental retardation, and related
      disabilities: ethics and efficacy.
AB  - TOPIC: Ethical debates concerning the use of aversive versus nonaversive behavior
      management continue among those who treat children with autism, mental
      retardation, and related disabilities. PURPOSE: To identify and discuss the crux
      of the aversive versus nonaversive debate by defining relevant terminology,
      examining assumptions and arguments that influence treatment approaches, and
      exploring the efficacy of nonaversive behavior modification techniques. SOURCES:
      A case study to illustrate the use of aversive and nonaversive techniques and to
      compare the findings of these different approaches to treatment CONCLUSIONS: As
      front-line interveners, nurses need to be aware of underlying philosophical and
      ethical issues if they are to implement the most effective treatment strategies
      while serving as advocates for the long-term welfare of children and their
      families.

PMID- 8868843
TI  - Ethical responsibility for the community's mental health: a professional nursing
      role.
AB  - TOPIC: A review of data from multiple sources indicates a decline in support
      services for children and families, and an increase in the prevalence of
      psychiatric disorders as well as psychosocial problems among children. A
      discussion of trends reveals reforms that are reducing all healthcare
      expenditures and limiting the provision of publicly funded services. PURPOSE: To
      discuss the essential values of professional nursing and considers them as a
      basis for needed nursing action. CONCLUSION: Individual nurses have an ethical
      responsibility to take social, political, and economic actions to enhance
      community mental health. Specific strategies and approaches for doing so are
      presented.

PMID- 8868844
TI  - What example do we set?

PMID- 8868845
TI  - Goals of hospital treatment: staff and client perceptions.

PMID- 8868846
TI  - Why hospital mental health staff terminate employment.
AB  - TOPIC: How hospital mental health staff make the decision to terminate
      employment. METHODS: Subjects (N = 30) included mental health professionals
      formerly employed at a large Canadian psychiatric hospital. They were interviewed
      using Ebaugh's model of the role exit process to determine different dimensions
      of the existing process. FINDINGS: The role exit process tended to cover a
      considerable time span, with notable potential for reversing the decisions.
      CONCLUSION: Staff who terminate employment due to job-related circumstances could
      be retained if active problem-solving measures were undertaken by the staff
      member and appropriate administrative personnel.

PMID- 8868847
TI  - Bibliotherapy and beyond.
AB  - TOPIC: Using literature and television to promote mental health. PURPOSE: To
      expand readers' awareness of how literature can be used therapeutically. SOURCE:
      The author's personal experience hosting a TV program entitled, "Best Books in
      Town". CONCLUSIONS: Discussing literature can promote emotional catharsis, active
      problem solving, and personal insight in those who chose to participate.

PMID- 8868848
TI  - King's conceptual framework applied to a transitional living program.
AB  - TOPIC: How Imogene King's theory of Goal Attainment was used as a theoretical
      framework for conceptualizing the role and function of a Transitional Residential
      Program for severely and persistently mentally ill homeless individuals. PURPOSE:
      To demonstrate how a nursing theory can be applied in the development of mental
      health services. SOURCE: King's theory and associated concepts of personal
      system, perception, communication, interaction, transaction, role, time, space,
      growth, and development. CONCLUSION: Achievement of client goals is possible
      within a social system characterized by mutual goal setting between clients and
      staff.

PMID- 8868849
TI  - Essential components of the short-term psychiatric unit.
AB  - TOPIC: How nurses can meet the priority needs of the acute care clients during
      inpatient psychiatric hospitalizations that average five days. PURPOSE: To assist
      acute care nursing staff in reorganizing their caregiving to maximize therapeutic
      gains of clients in a minimum period of time SOURCE: Personal experience.
      CONCLUSION: Success in the short-term unit depends not only on the ability of
      nurses to stabilize clients in crisis, but also on their ability to provide
      linkage with aftercare services so the therapeutic process can be continued.

PMID- 8868850
TI  - Depression: dealing with the darkness.
AB  - TOPIC: A client's personal experience of depression presented in her own words.
      SOURCE: Case study. PURPOSE: To assist nurses to understand, accept, and reassure
      depressed clients and "offer themselves" in a caring and continuing relationship.
      CONCLUSION: Understanding depression allows nurses to respond in a way that is
      therapeutic.

PMID- 8868851
TI  - The basal ganglia and movement disorders.

PMID- 8868852
TI  - Mental health home visits for the elderly.
AB  - TOPIC: The nurse's role in providing mental health services to the elderly.
      SOURCE: The Mental Health Interventions Program. GOAL: To provide a viable model
      for providing these services. CONCLUSION: Nurses have the skills necessary to
      ensure that the elderly are recipients of quality mental health care.

PMID- 8868853
TI  - Psychiatric nursing in a rural outreach program.
AB  - TOPIC: A method of delivering mental health services to clients in rural areas
      PURPOSE: To describe the opportunities available for nurses to provide mental
      health services in rural areas SOURCE: Preliminary outcome data from program
      statistics and case studies CONCLUSION: Nurses were able to significantly
      decrease client hospitalizations and increase longevity in the community.

PMID- 8868854
TI  - Connection and disconnection in abusive relationships.
AB  - TOPIC: The way in which women's need for connection can lead to destructive
      relationships in which emotional and physical paralysis is characteristic.
      PURPOSE: To demonstrate how a woman's sense of disconnection that occurs in
      abusive relationships may be misinterpreted or worse, labeled and stigmatized, by
      healthcare providers. SOURCE: Theories of growth and development that emphasize
      how a woman's sense of self and value derive from being able to maintain highly
      empathic affiliations. CONCLUSION: The behavioral manifestation of disconnection
      must be understood so that healthcare providers can provide the most effective
      care possible.

PMID- 8868855
TI  - The symbolic and literal in schizophrenic language.
AB  - TOPIC: Differences between the symbolic, or poetic, and the literal in
      schizophrenic language. PURPOSE: To enhance the nurse's therapeutic effectiveness
      with these clients. SOURCE: Review of the literature. CONCLUSION: What often is
      perceived as literal language in schizophrenic communication is, in many cases,
      full of symbolic meaning.

PMID- 8868857
TI  - Defining aggression.

PMID- 8868856
TI  - West African beliefs about mental illness.
AB  - TOPIC: Traditional West African beliefs about the cause and treatment of mental
      illnesses. PURPOSE: To demonstrate how learning about West Africa's cultural
      beliefs allowed the instructor to teach psychiatric nursing in a way that
      integrated, rather than dismantled, the students' cultural beliefs. SOURCE:
      Content analysis of West African students' written assignments. CONCLUSION:
      Psychiatric/mental health nurses must understand the client's culture in order to
      understand the client.

PMID- 8868859
TI  - [Nurse on a Polynesian atoll].

PMID- 8868858
TI  - Pathoanatomy of schizophrenia.

PMID- 8868860
TI  - [The nurse and the night shift].

PMID- 8868861
TI  - [What is allergy?].

PMID- 8868862
TI  - [Desensitization].

PMID- 8868863
TI  - [Education of allergic children and their parents ... in their own environment].

PMID- 8868864
TI  - [Allergic emergencies].

PMID- 8868865
TI  - [The nurse's role in the handling of flexible immersable endoscopes 1].

PMID- 8868866
TI  - -The nurse's role in anaphylactic shock-.

PMID- 8868867
TI  - [The emergency case, its contents, its use].

PMID- 8868868
TI  - [Distance: nurses facing AIDS 2].

PMID- 8868869
TI  - [Handwashing in a geriatric institution: myth or reality?].

PMID- 8868870
TI  - [Colloquia and congresses...].

PMID- 8868871
TI  - [Research and prevention].

PMID- 8868873
TI  - [How and with whom to study? ... or desperate search for experts].

PMID- 8868872
TI  - [Biomedical research: role and function of the nurse].

PMID- 8868875
TI  - [Know your anatomy ... know why you are in pain!].

PMID- 8868876
TI  - [Your back: learn to know it and to be responsible for it].

PMID- 8868877
TI  - [Gymnastics at home, it is up to you to do it].

PMID- 8868878
TI  - [The nurse's role in handling flexible immersible endoscopes. 2. Disinfection
      techniques].

PMID- 8868879
TI  - [Basic rules for practicing a sport].

PMID- 8868880
TI  - [Questions/answers ... or looking for signs of patient satisfaction].

PMID- 8868881
TI  - [Psychological tests... for better or worse].

PMID- 8868882
TI  - [The psychological experience of children with cancer].

PMID- 8868884
TI  - Professional development. Organisation of nursing care: professional issues
      (continuing education credit).

PMID- 8868883
TI  - [The disciples of Aesculapius and Thalia. Claude Bernard and Charles Richet].

PMID- 8868885
TI  - Have badge, will travel.

PMID- 8868886
TI  - Lost and found.

PMID- 8868887
TI  - Nursing overseas. Cultural exchange.

PMID- 8868888
TI  - Nursing overseas. Damage limitations.

PMID- 8868889
TI  - Nursing overseas. American advances.

PMID- 8868890
TI  - Extent and effectiveness of the Scope of Professional Practice.
AB  - This paper describes a survey commissioned by the NHS Executive (West Midlands
      office) Nursing Directorate in conjunction with the Research and Development
      Directorate. The study aimed to explore the extent of initiatives associated with
      the UKCC's Scope of Professional Practice in 58 trusts in the West Midlands. The
      data were produced through semi-structured interviews with professional heads of
      nursing, professional development staff and educators, together with postal
      questionnaires to a sample of 100 clinical managers in all branches of nursing
      and midwifery. The results indicate that the activities associated with the Scope
      of Professional Practice are not easily defined. There is support for the UKCC
      document, although there are reservations about the forces behind it, and
      insufficient resources are an obstacle to role and practice developments. To gain
      the most benefit from this initiative, it is argued, nursing and midwifery
      practitioners must plan the development of their roles carefully.

PMID- 8868891
TI  - Treating obesity in people with learning disabilities.
AB  - Obesity in people with learning disabilities should not be dismissed as
      untreatable. Such people have the same right to a healthy weight as the rest of
      the population. Equally, they should have the right to remain overweight if they
      so choose, provided their choice is an informed one. This paper reviews the
      reasons people with learning disabilities may become obese, addresses how this
      problem may be tackled and highlights some of the ethical issues involved in
      weight reduction for this client group.

PMID- 8868893
TI  - Say no to the easy answer.

PMID- 8868892
TI  - Elderly counts. Back on track.

PMID- 8868894
TI  - Education. Practical matters.

PMID- 8868895
TI  - Education. Contract to learn.

PMID- 8868896
TI  - Critical care. Inotrope therapy.

PMID- 8868897
TI  - Critical care. Intensive care unit syndrome.

PMID- 8868899
TI  - Anger at 'mini-doctor' jibe.

PMID- 8868898
TI  - Man trouble.

PMID- 8868900
TI  - The rationing myth.

PMID- 8868901
TI  - Time to care.

PMID- 8868902
TI  - A national perspective.

PMID- 8868903
TI  - No way out.

PMID- 8868904
TI  - Don't break the heart of the NHS.

PMID- 8868905
TI  - Doing everything for Tommy.

PMID- 8868906
TI  - Guidelines on cancer care.

PMID- 8868907
TI  - Improving delivery of care through change management.
AB  - This article describes an evidence-based care initiative and programme of
      clinical change which set out to improve the delivery of nursing care and related
      health outcomes for mentally disordered offender patients at Rampton Hospital.
      The programme has implications for all nursing specialties with studies also
      validated in mainstream psychiatric and general nursing contexts.

PMID- 8868908
TI  - Collaborating on the integration of cancer nursing services.
AB  - This article outlines the proposals contained in the Calman-Hine report (DoH
      1995), and then presents the work of a nursing task group set up in response to
      its recommendations. The authors describe how different agencies collaborated in
      a network approach to improving the provision of cancer services.

PMID- 8868909
TI  - Developing nursing knowledge and language.
AB  - This article describes how Watson's theory of caring (1988) can be used to talk
      about nursing and to consolidate learning. The author shows how students can
      reflect on clinical experiences to create personal nursing knowledge which, in
      turn, can generate new knowledge which is grounded in practice. The article is
      based upon the content of a curriculum unit taught at the author's college.

PMID- 8868910
TI  - Informed consent and the treatment of children.
AB  - This article explores the issue of informed consent prior to treatment and
      procedures for children under 16 years of age. Literature on the subject is
      reviewed and the author discusses the different attitudes to consent found among
      healthcare professionals. Recommendations on how to involve children in decision
      making are also made.

PMID- 8868911
TI  - Resuscitation: advanced life support (continuing education credit).

PMID- 8868912
TI  - Time for national debate.

PMID- 8868913
TI  - Trusting in leadership.

PMID- 8868915
TI  - Tough choices.

PMID- 8868914
TI  - A price we must never pay again.

PMID- 8868916
TI  - Delivering packages.

PMID- 8868917
TI  - The birth of a campaign.

PMID- 8868918
TI  - Providing the feel good factor.

PMID- 8868919
TI  - Preventing falls and further injury in older people.

PMID- 8868920
TI  - A study of nurses' knowledge of the UKCC code of conduct.
AB  - This study investigated nurses' and midwives' knowledge of the Code of
      Professional Conduct (UKCC 1992). Knowledge was assumed to be dependent on
      practitioners' abilities to identify correctly authentic statements and to
      discriminate against statements which were constructed as distracters. Generally,
      there was a relatively high mean of correct identification. Certain spheres of
      responsibility were more likely to be identified than others. These areas
      involved statements that were practitioner-centred and occurred early in the
      code. The authors recommend further research into nurses' understanding of the
      code.

PMID- 8868921
TI  - Developing outcome indicators in continuing care: part 2.
AB  - In their follow-up to last week's article which described the development of
      outcome indicators for nursing older people in continuing care settings, the
      authors describe in detail the process of indicator development. Referring to
      theoretical models, they provide a practical example of how a nurse could use one
      of his or her experiences from nursing to illustrate the distinct value of
      patient interventions provided by a registered practitioner.

PMID- 8868922
TI  - Guidelines for producing patient information literature.
AB  - This article provides practical information on developing patient information
      literature. The step-by-step approach provided by the authors should be of use to
      nurses who are currently involved in producing such literature or who are looking
      at ways of effectively disseminating information to patients on specific topics.

PMID- 8868924
TI  - Are you being served?

PMID- 8868923
TI  - Patient-controlled analgesia (continuing education credit).

PMID- 8868925
TI  - A council for carers.

PMID- 8868927
TI  - A spectator sport.

PMID- 8868928
TI  - Fighting for acceptability. Interview by Charlotte Alderman.

PMID- 8868929
TI  - An unwanted concept.

PMID- 8868930
TI  - Injury caused by lifting: a study of the nurse's viewpoint.
AB  - This article reports the findings of a questionnaire survey of work-injured
      nurses. Thirty nurses reported back injury caused by lifting and nine causative
      factors were identified in significantly more than 20 per cent of accidents. The
      threshold of reported weight at which accidents began to happen was 50.9kg.
      Nurses were found to be particularly at risk when mobilising patients because
      walking accidents are not preventable by using non-lifting techniques. The
      findings suggest that nurses should be equipped with the appropriate levels of
      expertise in assisting patients with mobilising.

PMID- 8868931
TI  - Developing outcome indicators in continuing care: part 1.
AB  - In the first of two articles, the authors describe the development of outcome
      measures for nursing older people in a continuing care setting. They describe why
      such a process was initiated and the framework which guided the project,
      including current nursing and government policy and theories of knowledge and
      expert practice. The second article will appear next week.

PMID- 8868932
TI  - Childhood accident prevention: putting audit into practice.
AB  - This article describes an audit of children presenting at accident and emergency
      departments following an accident. The authors explain how the audit data
      informed a strategy for childhood accident prevention schemes in Newcastle for
      1995/96.

PMID- 8868933
TI  - Urinalysis: ensuring accurate urine testing (continuing education credit).

PMID- 8868934
TI  - [Assessing and measuring language development in the child. The Reynell Scales in
      a Dutch language area].
AB  - This article deals with the recent adaptation of the Reynell Developmental
      Language Scales to the Dutch language. The existing language tests for the Dutch
      language are reviewed and the need to adapt a test for young children, measuring
      both receptive and expressive language development, is argued. The adaptation of
      the original Reynell Developmental Language Scales to the Dutch language is
      described. An extensive standardisation was carried out with 1,288 Dutch-speaking
      children, carefully selected geographically and according to socio-economic
      status. The psychodiagnostic results of the standardisation are discussed. As a
      result there are now norms for children between 2 and 5 years, both for receptive
      and expressive language development. The adaptation of the original Reynell
      Scales to Dutch functions under the new name RTOS (Reynell
      Taalontwikkelingsschalen).

PMID- 8868935
TI  - Early speech development, articulation and reading ability up to the age of 9.
AB  - Speech development, the occurrence of articulatory errors, speech therapy
      received and literacy were evaluated in children at preschool and school age.
      Data were obtained with questionnaires sent to the parents and teachers of 1,708
      second-grade children in 119 school classes selected by multistage random
      sampling among Finnish-speaking schools throughout the country. Completed
      questionnaires were received from 1,531 parents (89.6%) and 1,601 teachers
      (93.7%). Early speech development was slower among the boys than among the girls.
      The proportion of children with articulatory errors decreased from 32.5% at the
      age of 5 years to 18.4% at 7 years and 7.4% at 9 years, and the boys had more
      articulation problems than the girls. Errors in two or more sounds at school age
      were rare, and more than 90% of all errors were in the sounds /r/, and /s/. About
      one fourth of the girls (26.7%) and one sixth of the boys (18.1%) had gained
      preschool literacy; 2.9% of the girls and 6.6% of the boys were still not able to
      read fluently by the middle of the fourth term. The difference between the sexes
      was seen both in the early development of speech and articulatory problems and in
      literacy at the age of 9.

PMID- 8868936
TI  - Tremor in stutterers.
AB  - The author investigated the subclinical tremor on the extremity muscles in
      stutterers at rest, without speaking. This tremor occurred in the native EMG
      record from the musculus abductor digiti quinti during isometric contraction.
      Because it occurred in a muscle not involved in speaking and moreover at rest,
      without speaking, the author excludes the possibility that it could be an
      increase in the amplitude of physiological tremor; she concludes that the cause
      of this tremor are changes in the function of the structures responsible for
      motor feedback, especially in the extrapyramidal and cerebellar field.

PMID- 8868937
TI  - On the effects of various vocal training methods on glottal resistance and
      efficiency. A preliminary report.
AB  - The glottal resistance, i.e. the ratio of subglottic pressure to glottal flow,
      and the laryngeal efficiency, i.e. the ratio of oral acoustic power to
      aerodynamic subglottal power (multiplication of subglottig pressure and glottal
      flow), were measured for 11 subjects (3 males) with normal voices and for 1
      female patient with glottal insufficiency in the repeated production of the
      nonsense word /paappa/ immediately before and after 1 min of vocal exercising
      with /beta:, m:/ and phonation into a narrow glass tube. For the subjects with
      normal voices the glottal resistance decreased in most cases and the laryngeal
      efficiency in half of the cases due to increased glottal flow. In contrast, for
      the patient the glottal resistance and efficiency increased due to decreased
      glottal flow. The results suggest that the vocal exercises instantly affected the
      control of the glottal width.

PMID- 8868938
TI  - Phonation into a tube as a voice training method: acoustic and physiologic
      observations.
AB  - Phonation into narrow glass tubes has been used as a voice training method. The
      present study examined phonatory and voice quality during and after tube
      phonation. The methods used were (a) electromyography with surface electrodes,
      (b) a dual-channel electroglottography from which the vertical larynx position
      was derived and (c) inverse filtering of the acoustic signal of vowel samples
      produced before and immediately after the exercise. Phonation into a tube seemed
      to cause a tendency to heighten the vertical laryngeal position. For female
      subjects (n = 3) the tube exercise tended to lead to increased vocal effort in
      vowel production after the exercise and, in contrast, to a tendency for a more
      relaxed voice production for the males (n = 2).

PMID- 8868939
TI  - [Apropos of the studies of Lewis, Nusslein-Volhard and Wieschaus, 1995 Nobel
      prize winners, on the genetic mechanisms of embryonic development of drosophila.
      A model for human cancer progression].
AB  - EB Lewis, C Nusslein-Volhard and E Wieschaus were the winners of the Nobel prize
      in 1995 for the discovery of genes controling the embryonic development in
      drosophila. Drosophila development is dependent on sequential activities of three
      types of genes: the maternal genes, the segmentation genes, and the homeotic
      genes which are responsible for the segment identity and finally for the building
      of the body. Mutations of these genes are spectacular because they affect the
      body structure formed from individual segments. Therefore, the molecular
      processes regulating the development of inferior organisms such as yeast or more
      complex as the vertebrates were elucidated by these three researchers. These
      early biological mechanisms regulate the cell life through interactions with
      neighbouring cells. We speculate that any alteration of these processes might be
      implicated in cancer. Understanding of these molecular mechanisms which control
      cell interactions in cancer constitutes a basis for definition of new prognostic
      markers and putatively novel therapeutic approaches.

PMID- 8868940
TI  - [Immune reactivity and anergy in breast cancer].

PMID- 8868941
TI  - [Multiple myeloma and bone manifestations. Role of clodronate].
AB  - Osteolytic lesions in multiple myeloma are related to osteoclast activation
      induced by a network of cytokines including IL6, TNF beta or IL1 beta which
      explain pain, fractures, or hypercalcaemia appearance. Bone destruction is
      reflected by hydroxyprolinuria and inversely correlated with serum osteocalcin.
      Lytic lesions or osteopenia are present in 80% of patients on X-ray. MR imaging,
      is interesting for exploring spinal lesions or the so-called solitary
      plasmacytomas but still remains a tool in evaluation. After therapies few
      modifications are demonstrated on roetgenograms while osteodensitometry appears
      more sensitive. A review of the literature is made showing the prominent place of
      clodronate in the therapy of hypercalcaemia of multiple myeloma. This drug
      appears attractive for decreasing osteolysis and perhaps for improving quality of
      life of patients. Nevertheless, a better definition of its use in clinical
      practice is necessary.

PMID- 8868942
TI  - [Myelodysplasia and tuberculosis].
AB  - We report here the case of a patient with myelodysplasia and concomitant
      tuberculosis. Refractory anemia with blasts excess diagnosis was based upon
      morphological and cytogenetical criterias (del 20q), and tuberculosis was
      diagnosed on a cervical lymph node biopsy. Hematological data remained stable
      without any specific treatment for several months, cell counts even normalized
      under antituberculosis tritherapy. Clinical and hematological worsening appeared
      3 years later, 1 year after discontinuation of antituberculosis therapy. It was
      characterized by progressive bone marrow failure and transformation in acute
      myeloid leukaemia. Concomitantly tuberculosis relapsed. The association of
      antituberculosis therapy and polychemotherapy (daunorubicine and aracytine) did
      not allow to obtain a hematological remission. The relationship between
      tuberculosis and myelodysplasia is discussed.

PMID- 8868943
TI  - [CAL 54, a new cell line derived from a human renal carcinoma: characterization
      and radiosensitivity].
AB  - A new cell line (CAL 54) was isolated from a malignant pleural effusion of a
      patient with renal carcinoma. CAL 54 is a continuous and stable cell line.
      Immunochemical staining showed simultaneous expression of cytokeratin, epithelial
      membrane antigen and vimentin. Cytometric flow analysis of DNA content reveals
      one major hyperdiploid population. Histological aspect of the tumor induced in
      the nude mouse showed well differentiated adenocarcinoma with papillary
      structure. Radiation response of these cells was evaluated by the colony-forming
      method and the data were fitted with the linear-quadratic model. Survival at 2 Gy
      (SF2) was 0.28 and the mean inactivation dose (D) = 1.50 Gy, ranking this cell
      line among the radiation sensitive cells. CAL 54 may be an informative cell line
      to investigate radiation effects in the management of renal tumours.

PMID- 8868944
TI  - [Predictive value of the hemogram for myelotoxicity induced by the association of
      carboplatin-fluorouracil on the 4th day of the therapeutic regimen].
AB  - The aim of this study was to determine the value of haematological counts at the
      4th day of a chemotherapy cycle, in order to foresee neutro and/or
      thrombocytopenia during the same chemotherapy cycle. One hundred and ten cycles
      of chemotherapeutic regimens with carboplatin (400 mg/m2, dl) and 5-fluorouracile
      (1 g/m2/d, by iv continuous infusion for 96 hours) every 3 weeks, were analyzed
      for 42 patients with locally advanced but non metastatic squamous cell carcinoma
      of head and neck, without prior chemotherapy. Lymphocyte counts were
      significantly decreased at the 4th day but normalized at the 8th day (P < 10(
      6)). Decreases of lymphocyte and neutrophil counts at the 4th day were
      significantly correlated to grade > 2 neutropenia. The positive predictive value
      of lymphocyte or neutrophil counts is about 50% for some cut-off values but not
      high enough, with the schedule of chemotherapy in our study, to justify the
      systematic prophylactic therapy with haematopoietic growth factors.

PMID- 8868946
TI  - [Role of microbiopsies in the therapeutic and diagnostic approach in cases of
      mammary microcalcification: preliminary results].
AB  - The increase of mammographies has lead to the discovery of more frequent mammary
      microcalcifications. Presently, about 30% of breast tumors are discovered from
      infraclinics lesions. Instead of the different classifications, the
      microcalcifications are the omnious sign with bad specificity. It is in the aim
      to improve the diagnostic etiology and the choice of therapy, that the directed
      microbiopsies on microcalcifications had been realized. After an orthogonal
      location and under local anesthesia, we performed at least six biopsies with a
      2.1 mm (14 gauge) needle. This allowed recovery of malignant lesions during the
      control of microcalcifications and permitted considerable early operative
      treatment. In fact, a diagnostic and therapeutic advancement of 12 months as
      compared to a clinical diagnosis, permitting a 30% reduction of metastasis.

PMID- 8868945
TI  - [Carboplatin and cyclophosphamide in stage Ic-IV ovarian carcinoma: retrospective
      study of 101 cases].
AB  - We report our experience of CBDCA-CPM combination chemotherapy as first line
      therapy in 101 ovarian cancers. The therapeutic scheme was: initial cytoreductive
      surgery followed by six chemotherapy cycles (CBDCA 400 mg/m2/d IV dl, CPM 600
      mg/m2/d IV dl, dl = d21) and second-look laparotomy. The initial stages were four
      Ic, three IIa, four IIb, four IIc, 15 IIIa, 28 IIIb, 23 IIIc and 20 IV. After
      initial surgery, there were 39 macroscopic residual diseases superior to 2 cm, 26
      macroscopic residual diseases inferior or equal to 2 cm, four microscopic
      diseases and no residual disease in 30 cases (unknown in two cases). The overall
      response rate to chemotherapy was 83% with 56% histologic complete response rate.
      The main toxicity was haematological with 60% of leucopenia grade III-IV, 52% of
      thrombopenia grade III-IV. Age at diagnosis, residual disease after first look
      surgery and length of CA 125 normalization were significant prognostic factors
      for survival in this series.

PMID- 8868947
TI  - [Axillary lymph node dissection in clinically occult breast cancer].
AB  - The study concerns 265 patients with axillary lymph node dissection for non
      palpable breast cancer. The mammographically detected breast tumors were: 36
      ductal carcinomas in situ (DCIS), 23 microinvasive carcinomas, 206 invasive
      carcinomas of which 179 were invasive ductal cancers (IDC), 25 invasive lobular
      cancers (ILC) and 2 mucinous invasive carcinomas. The histologic size of the
      invasive component was < or = 5 mm in 38 cases, 6-10 mm in 84 cases, 11-15 mm in
      53 cases, 16-20 mm in 16 cases, > 20 mm in 15 cases. Axillary dissection was
      performed immediately during the initial surgical procedure in 209 patients (79%)
      or secondarily in 56 (21%) according to the results of intraoperative examination
      of surgical specimens on frozen sections. Axillary lymph node involvement was not
      found in DCIS, microinvasive carcinomas or invasive carcinomas < or = 5 mm in
      size. Among all 206 invasive breast carcinomas, lymph node involvement was found
      in 7.8% (16/206) of cases. There were 9/84 (10.7%) in tumors > 10 mm, 7/122
      (5.8%) in tumors < or = 10 mm. Thus, it is concluded that lymph node involvement
      is unlikely to be found in patients with non palpable breast cancers, specially
      those with carcinoma in situ, microinvasive breast tumors and invasive breast
      cancer with less than 5 mm maximum diameter size. Axillary dissection may be
      avoided in these patients. However, the use of new prognostic factors of lymph
      node involvement may help in the definition of patient group.

PMID- 8868948
TI  - Establishment of an in vitro cell derived from human angiosarcoma.
AB  - We have succeeded in the establishment of a human endothelial cell line derived
      from a human angiosarcoma. These cells grew as monolayers with a "cobble stone"
      morphology. The cells produced endothelin and showed Weibel-Palade bodies in
      their cytoplasm. These findings show that the cells have specific differenciated
      functions, and might be useful for both fundamental endothelial cell biology and
      biological investigation of angiosarcoma.

PMID- 8868949
TI  - [Use of percutaneous anesthesia in cardiac pacemaker implantation].
AB  - OBJECTIVES: Assess the efficacy of an anesthesic cream for pacemaker
      implantations. METHODS: Percutaneous anesthesia was studied in a series of
      permanent pacemaker transvenous implantations. The anesthesic cream composed of a
      mixture of lidocaine and prilocaine was applied precisely over operative areas
      after marking the skin. Percutaneous anesthesia should be applied 2 hours before
      entering the operating room. RESULTS: This percutaneous local anesthesia was
      perfectly effective for simple replacement procedures. At first implantations, it
      was used alone in 4 out of 10 cases while intradermal injections were needed to
      anesthetize the deep layers in the other patients. Serum concentrations indicate
      very low levels which are tolerated very well. CONCLUSION: Alone or combined with
      lidocaine infiltration, the use of an anesthesic cream is safe and effective in
      transvenous pacemaker surgery.

PMID- 8868950
TI  - [Prescription of diphosphonates in ambulatory oncology. A study of the health
      insurance medical services].
AB  - OBJECTIVES: As requested by the Health Ministry, the Agricultural (Mutualite
      Sociale Agricole) and Independant Professions (Assurance Maladie des Professions
      Independantes) Health Insurances carried out a survey to analyse the use of
      second generation oral biphosphonates. METHODS: The data, from 3,414
      prescriptions, gathered over the twelve months from May '93, showed that
      clodronate is prescribed mainly for breast cancer (35%), prostate cancer (23%),
      multiple myeloma (19%) and carcinoma of the lung (7%). The other prescriptions
      (16%) were either related to various malignant diseases (18 types encountered) or
      non-malignant diseases (mainly osteoporosis, but also Paget's disease of bone and
      hyperparathyroidism). The initial prescriber was most often a cancerologist (49%)
      but also quite frequently (17%) a general practitioner. The treatment was
      prescribed for an average of 41 days. 1600 mg daily was the most frequent dose
      (79%). However, in non-authorised indications, especially osteoporosis, the dose
      was lower, generally 800 mg a day. Altogether 14% non-authorised indications were
      linked either to non-metastatic malignant diseases (for the prevention of
      metastases) or with osteo-condensing type metastases (prostate cancer: 43%) or
      non-malignant diseases (osteoporosis, Paget's disease of bone,
      hyperparathyroidism, chronic renal insufficiency, sympathetic algodystrophy,
      bedbound decalcification, etc.). The prescription for these cases was motivated
      by the expected beneficial effect on bone mineralisation. Such treatment
      authorised was more often initiated by a general practitioner (23%) than a
      specialist (12%). CONCLUSION: These data raise the problem of limiting the
      possibility of prescribing second generation biphosphonates as initial treatment
      to a specialist. They also reaffirm the need to have precise guidelines in the
      field of medical prescription controls.

PMID- 8868951
TI  - [Value of C-reactive protein for detecting bacteremia in febrile patients].
AB  - OBJECTIVES: Mortality among bacteremic adults ranges between 14 and 35%, and
      there is no biological clue to identify such patients a priori. As C-reactive
      protein (CRP) blood level rises in children during bacteremia, we investigated
      its accuracy to identify bacteremic patients among febrile adults who were
      admitted to our hospital either for study or treatment. METHODS: Patients older
      than 14 entering the emergency room with objective axilar temperature above 37.5
      degrees C and admitted either for study or treatment were elligible for
      enrollment. After initial examination, samples were obtained for blood cultures
      and CRP measurement. Follow-up during hospitalization was assessed. All variables
      were related with one another by bivariant statistical methods performed with
      Sigma Horus hardware. After bivariant study we used the program BMDP Statistical
      Software (1991) to perform the multivariate study in its discriminant analysis.
      RESULTS: One hundred seventy-four patients entered the study with an average age
      of 58.9 years; 47.7% were over 65 years of age; 88% of febrile syndromes were of
      infectious origin and among them, bacteremia ranged up to 17.2%. Values of CRP
      were significantly related with the following variables: "age": patients younger
      than 45 had average CRP concentrations of 9.5 mg%, age over 45 had 17.4 mg% (Mann
      Whitney U (MW) p < 0.001); "clinical situation on admission": for poor,
      intermediate and stabilized situations average CRP levels were 14.7, 18.5 and
      12.4 mg% respectively (MW p < 0.05); "time from fever onset"; "clinical outcome":
      for death average CRP was 23.01 mg% and for cure 14.6 mg% (MW, p < 0.05), in that
      way probability of death was 21%, 9% and 3% for CRP concentrations higher than
      20, between 10 and 20 and under 10 mg% respectively. There was no link between
      CRP serum levels and sex, severity of chronic illness, cause of fever,
      localization of infection and existence of bacteremia. The multivariate study in
      its discriminate mode was of no use to identify bacteremic patients. CONCLUSION:
      According to our findings CRP determination can not be used alone or associated
      to identify patients with positive blood cultures among the febrile ones. CRP
      blood determination should not be considered before 24 hours from disease onset
      as this time is required for CRP to stabilize. Patients with CRP levels higher
      than 20 mg% on admission have a higher risk of dying during hospitalization.

PMID- 8868952
TI  - [Spiral X-ray computed tomography: a new modality of scanner imaging].
AB  - Spiral computed tomography is a new imaging modality that presents several
      advantages when compared to conventional and dynamic computed tomography. It
      consists in a continuous rotation of the X-Ray tube around the anatomical area to
      be explored, simultaneously with a move of the examination table at a constant
      speed. Advantages are the short acquisition time (below one minute), optimization
      of the intravenous injection of the iodinated contrast material, acquisition of a
      gapless volume of data which can be post-processed, permitting axial
      reconstructed sections which are perfectly contiguous, as well as an easy access
      to 2D multiplanar and 3D reconstructions, with the benefit of a substantial
      decrease in patients' radiation. This paper will review the prominent advantages,
      as well as the current limitations, of this new imaging modality.

PMID- 8868953
TI  - [Shoshin beriberi. A rapidly curable hemodynamic disaster].
AB  - Shoshin beriberi, a uncommon cause of hemodynamic instability (or cardiac shock)
      and acute heart failure may go undiagnosed in Western countries where prevalence
      is low. This severe heart condition due to thiamine deficiency is rapidly fatal
      unless specific therapy is given. The most frequent cause in France is chronic
      alcoholism. There are no specific signs on the electrocardiogram in a patient
      with acute heart failure due to shoshin beriberi. The chest x-ray simply shows
      signs of pulmonary edema and heart enlargement. The echocardiography may be
      normal although hypokinesia and/or dilatation of the left ventricle (due to
      thiamine deficiency) are sometimes noted. Diagnosis is suspected in patients with
      chronic alcoholism who develop acute global heart failure with lactic acidosis.
      Right catheterism confirms low cardiac output resulting from arteriovenous
      shunts. Blood tests (red cell transacetolase activity, measurement of effect of
      pyrophosphatase, plasma and intraerythrocyte thiamine) confirm the diagnosis a
      posteriori. Clinical improvement is rapid after intravenous infusion of vitamin
      B1. The danger of fulminant beriberi heart failure in undernourished alcoholic
      patients emphasizes the need for regular prescription of vitamin B1.

PMID- 8868954
TI  - [Treatment of arterial hypertension in diabetic nephropathy. Certainties and
      hypotheses].
AB  - Clinical observation has long emphasized the importance of arterial hypertension
      in the course of diabetic nephropathy and recent studies suggest that
      hypertension might play a decisive pathogenetic role in the course of the
      disease, hence the necessity of correcting the hypertension of diabetic patients
      has by now been universally accepted. There is, however, still some uncertainty
      concerning the usefulness of acting preventively on so-called microhypertension;
      in other words, whether early antihypertensive drug treatment can prevent
      diabetic nephropathy. This paper discusses the criteria to be followed in the
      choice of antihypertensive medication during diabetic nephropathy giving special
      attention to pathophysiological considerations. Moreover, it also discusses the
      effects of antihypertensive drugs currently regarded as first-choice agents, i.e.
      calcium antagonists and the angiotensin converting enzyme inhibitors, on
      intrarenal hemodynamics.

PMID- 8868955
TI  - [Chronic gastritis with presence of Helicobacter heilmannii].

PMID- 8868956
TI  - [Abortion in a woman with hyperimmunoglobulin D syndrome].

PMID- 8868957
TI  - [Efficacy of pyrimethamine in monotherapy for preventing toxoplasmosis in AIDS].

PMID- 8868958
TI  - [Digitalis poisoning in a patient with septic shock: value of plasma exchange].

PMID- 8868959
TI  - [Ascites disclosing Crohn disease].

PMID- 8868960
TI  - [Portal thrombosis in a patient with Vaquez disease and factor V Leiden].

PMID- 8868961
TI  - [Aspirin during pregnancy in women at risk of pregnancy-induced hypertension].

PMID- 8868962
TI  - [Cancer treatment--is there progress?].

PMID- 8868963
TI  - [Endothelins].

PMID- 8868964
TI  - [Melatonin. Hormone or wonder drug?].

PMID- 8868965
TI  - [Depression. The incidence is underestimated--treatment is inadequate].

PMID- 8868966
TI  - [Panic disorder].

PMID- 8868967
TI  - [Insulin resistance--possible causes and effects].

PMID- 8868968
TI  - [Results of research on therapeutic factors and treatment effectiveness of group
      therapy with adolescent patients].
AB  - Group therapy with adolescents suffers from a lack of empirical studies although
      this specific therapeutic setting has been described in clinical reports as
      particularly beneficial. This article provides a survey of available controlled
      outcome- and process-studies in group therapeutic settings with adolescents
      covering publications up to 1992. Future research topics in adolescent group
      therapy investigations are being discussed while comparing results and questions
      of group therapy research with adult clientels and their possible application to
      research with adolescents in groups.

PMID- 8868969
TI  - [Psychological aspects of severe burn injuries in childhood and adolescence].
AB  - Severe burn injuries are the most painful injuries known, and treatment
      procedures can be extremely aversive as well. Pediatric burn suvivors must often
      live with permanent disfigurement und physical disabilities. This article
      presents a review of psychological aspects of severe burn injuries in children
      and adolescents. The review is based on the scientific literature and own
      professional experiences. After discussing predisposing factors of burn injuries
      three phases of medical therapy are defined: 1) acute phase, 2) phase of surgical
      therapy and 3) phase of rehabilitation. For each of these stages common
      psychological reactions and potential psychological interventions are presented.
      Finally psychosocial sequelae and longterm adjustment of pediatric burn injuries
      are described and implications for the psychological treatment of burned children
      and adolescents are discussed.

PMID- 8868970
TI  - [Case study of treatment of school phobia using a varied stress confrontation
      procedure].
AB  - Starting from one case for treatment, the phenomenon of school phobia (separation
      anxiety) is being discussed as to the definitional, diagnostic, and therapeutic
      aspects involved. The author attempts to classify school phobia within a
      behavioral framework. The development of separation anxiety is then being
      explained under a hypothesis model. For diagnostic and therapeutic purposes an
      orienting framework is being sketched out which takes into account practical
      experience as well as research evidence.

PMID- 8868971
TI  - Detection and prevention of myocardial damage during open heart surgery.

PMID- 8868972
TI  - Transmyocardial revascularisation.

PMID- 8868973
TI  - Tissue Doppler echocardiography.

PMID- 8868974
TI  - Does Doppler myocardial imaging give new insights or simply old information
      revisited?

PMID- 8868975
TI  - The need for artificial hearts.
AB  - Chronic immunosuppression, allograft coronary disease, and restricted
      availability of donor organs continue to limit the scope of cardiac
      transplantation. Meanwhile increasingly favourable experience with implantable
      blood pumps used as a bridge to transplant has reintroduced the concept of
      permanent mechanical cardiac support. Existing models (for example, the Thermo
      Cardiosystems Heartmate device) are now used for such support in patients who are
      not candidates for transplantation. Miniaturised axial flow pumps such as the
      Jarvik 2000 fit within the failed left ventricle and provide an exciting prospect
      for the treatment of heart failure in the future. Preliminary experience suggests
      that the "offloaded" left ventricle may recover. Mechanical blood pumps can be
      used before the onset of multisystem failure and removed if the myocardium
      recovers. This "bridge to recovery" concept should be tested in patients with
      recoverable cardiomyopathy and those with coronary disease and poor left
      ventricular function where an implantable pump can be used in conjunction with
      myocardial revascularisation.

PMID- 8868976
TI  - Can clonidine, enoximone, and enalaprilat help to protect the myocardium against
      ischaemia in cardiac surgery?
AB  - OBJECTIVE: To evaluate whether clonidine, enoximone, and enalaprilat reduce
      ischaemia-related myocardial cell damage in cardiac surgery. DESIGN: Prospective
      randomised controlled trial. SETTING: Clinical investigation in a cardiac
      anaesthesia department of a university hospital. PATIENTS: 88 consecutive
      patients undergoing coronary artery bypass surgery. INTERVENTIONS: After
      induction of anaesthesia patients continuously received the alpha 2 agonist
      clonidine (group 1, n = 22), the phosphodiesterase (PDE) III inhibitor enoximone
      (group 2, n = 22), the angiotensin converting enzyme (ACE) inhibitor enalaprilat
      (group 3, n = 22), or saline solution as placebo (control group, n = 22). The
      infusion was stopped immediately before the start of cardiopulmonary bypass. MAIN
      OUTCOME MEASURES: The ST segment was analysed and the activity of creatine kinase
      isoenzyme MB (CKMB), cardiac troponin T (TnT), and the BB isoenzyme of glycogen
      phosphorylase (GPBB) were measured before the start of infusion (baseline), after
      weaning from cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB,
      and on the morning of the first and third postoperative days. RESULTS: Biometric
      data and time of cross-clamping were not significantly different in the four
      groups. Changes in the ST segment indicating ischaemia were least common in the
      enalaprilat group (P < 0.05). Postoperatively, CKMB activity was significantly
      higher in the clonidine and the control groups. Both new markers of myocardial
      cell damage increased more after CPB and postoperatively in the control patients
      (TnT peak: (mean (SD)) 3.99 (0.35) microgram/1; GPBB peak: 82 (15) ng/ml) and the
      clonidine-treated group (TnT peak: 3.80 (0.3) microgram/1; GPBB peak: 85 (14)
      ng/ml). Enalaprilat-treated patients showed the smallest overall changes in
      standard (CKMB) and new serological markers of myocardial ischaemia (TnT peak:
      0.71 (0.1) microgram/1; GPBB peak: 44 (14) ng/ml). CONCLUSIONS: In patients
      treated with enalaprilat before CPB, both new, more sensitive markers of
      ischaemic myocardial tissue damage increased significantly less than in an
      untreated control group. Those treated with enoximone also had lower plasma
      concentration of TnT and GPBB than the control group, whereas clonidine did not
      reduce the concentration of these markers of myocardial ischaemia.
      Pharmacological interventions, such as the continuous infusion of the ACE
      inhibitor enalaprilat, before start of CPB may help to protect the heart against
      ischaemia/reperfusion injury.

PMID- 8868977
TI  - 3D construction from spiral CT scanning of pericardial calcification.

PMID- 8868978
TI  - Vulnerability of paediatric myocardium to cardiac surgery.
AB  - OBJECTIVE: Myocardial injury is an important cause of mortality and morbidity
      after paediatric cardiac surgery. Data obtained from studies in animals imply
      that juvenile myocardium is more resistant to the effects of ischaemia and
      reperfusion than adult myocardium but there is little confirmatory evidence in
      the clinical setting. DESIGN: Prospective observational study of biochemical
      markers of myocardial injury in a paediatric population undergoing cardiac
      surgery. SETTING: Tertiary referral centre for paediatric cardiac surgery.
      PATIENTS: Forty patients undergoing paediatric cardiac surgery of varying
      complexity including closure of atrial and ventricular septal defects and
      arterial switch for simple transposition. A control group included patients
      undergoing thoracotomy for closure of a patent ductus arteriosus or repair of a
      coarctation. INTERVENTIONS: Serial measurements of myoglobin, the MB isoenzyme of
      creatine kinase (CK-MB), and the highly specific markers of myocardial damage
      cardiac troponin T (cTnT) and I (cTnI) were made before and 1, 6, 24, and 48 to
      72 hours after operation. RESULTS: There were significant increases in myoglobin
      and CK-MB, but not cTnT or cTnI, in the control group. There were significant
      increases in the four biochemical markers in all the cardiac operations but
      especially in the ventricular septal defect and transposition group. Increases in
      CK-MB and cTnT were about five times greater than those previously reported in
      adult patients. CONCLUSIONS: (i) Cardiac troponins are more specific markers of
      myocardial injury in paediatric cardiac surgery than myoglobin and CK-MB. (ii)
      Paediatric myocardium seems to be more vulnerable to injury during cardiac
      surgery than adult myocardium.

PMID- 8868979
TI  - Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril
      treatment in patients with chronic heart failure.
AB  - OBJECTIVE: To assess non-invasively the effect of enalapril on cardiac
      sympathetic neuronal uptake function in patients with congestive heart failure,
      by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline
      analogue. Cardiac MIBG uptake was visualised by single photon emission tomography
      (SPET). In addition, plasma noradrenaline concentration, indicating systemic
      sympathetic activity, was measured to see whether it was related to cardiac MIBG
      uptake. DESIGN: Consecutive patients were treated with enalapril and served as
      their own controls. SETTING: Cardiac unit of a tertiary care centre. PATIENTS: 23
      Patients with chronic, mild to moderate, stable congestive heart failure, and a
      left ventricular ejection fraction less than 40%. Heart failure was caused by
      ischaemic heart disease or was idiopathic. INTERVENTIONS: Cardiac MIBG SPET was
      performed and plasma noradrenaline concentration was measured before and after 6
      weeks treatment with enalapril. MAIN OUTCOME MEASURES: Cardiac uptake of MIBG was
      measured by using the left ventricular cavity and a venous blood sample as a
      reference. RESULTS: Cardiac uptake of MIBG increased significantly after
      enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma
      noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake
      was not related to plasma noradrenaline concentration. CONCLUSIONS: Cardiac MIBG
      SPET can be used to assess changes in cardiac sympathetic neuronal uptake
      function caused by pharmacological intervention. Enalapril seemed to improve
      cardiac sympathetic neuronal uptake function but did not significantly affect
      plasma noradrenaline concentrations in a group of patients with predominantly
      moderate heart failure. These results accord with the hypothesis that restoration
      of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of
      enalapril in such patients.

PMID- 8868980
TI  - Effect of pimobendan on exercise capacity in patients with heart failure: main
      results from the Pimobendan in Congestive Heart Failure (PICO) trial.
AB  - PRIMARY OBJECTIVE: To determine the effects of pimobendan 2.5 and 5 mg daily on
      exercise capacity in patients with chronic heart failure. DESIGN: A randomised,
      double blind, placebo controlled trial of the addition of pimobendan to
      conventional treatment with a minimum follow up of 24 weeks. SETTING: Outpatient
      cardiology clinics in six European countries. PATIENTS: 317 patients with stable
      symptomatic heart failure, objectively impaired exercise capacity, and an
      ejection fraction of 45% or lower who were treated with at least an angiotensin
      converting enzyme inhibitor and a diuretic and who tolerated a test dose of
      pimobendan. RESULTS: Compared with placebo, both pimobendan 2.5 and 5 mg daily
      improved exercise duration (bicycle ergometry) by 6% (P = 0.03 and 0.05) after 24
      weeks of treatment. At that time 63% of patients allocated to pimobendan and 59%
      of those allocated to placebo were alive and able to exercise to at least the
      same level as at entry (P = 0.5). No significant effects on oxygen consumption
      (assessed in a subgroup of patients) and on quality of life (assessed by
      questionnaire) were observed. Pimobendan was well tolerated. Proarrhythmic
      effects (24-hour electrocardiography) were not observed. In both pimobendan
      groups combined the hazard of death was 1.8 (95% confidence interval 0.9 to 3.5)
      times higher than in the placebo group. CONCLUSIONS: Pimobendan improves exercise
      capacity in patients with chronic heart failure who are also on conventional
      treatment. The balance between benefit and risk of treatment with this compound
      remains to be established however.

PMID- 8868982
TI  - Changing from intensive anticoagulation to treatment with aspirin alone for
      coronary stents: the experience of one centre in the United Kingdom.
AB  - OBJECTIVE: To investigate whether an elective change in the anticoagulation
      protocol for patients with coronary stents affected clinical outcomes and length
      of hospital stay. DESIGN: Retrospective observational study of a consecutive
      series of patients treated with coronary stents over an 18 month period from
      April 1994 to October 1995. BACKGROUND: Intensive anticoagulation regimens are
      used in many UK centres to reduce the risk of coronary stent thrombosis. Recent
      data have called into question the necessity for full anticoagulation and
      favourable results have been reported with antiplatelet agents alone. The results
      from a tertiary referral centre were investigated during a period where an
      elective change in policy was made: an initial 70 patients were treated
      intensively with intravenous heparin and with warfarin and aspirin; subsequently
      94 were treated with aspirin and deployment of a high pressure balloon only.
      METHODS: Review of case notes, angiograms, and a database of intervention
      procedures and telephone interview. Classic epidemiological techniques, as well
      as linear regression and logistic regression, were used to model the outcomes of
      major procedural complications and length of hospital stay. PATIENTS: 164
      patients treated with 196 coronary stents. RESULTS: There were 22 (13.4%) major
      complications (coronary bypass grafting 11, subacute thrombosis 6, tamponade 2,
      myocardial infarction 1, death 2). With logistic regression, the risk of major
      complication was shown not to be affected by anticoagulation (relative risk (RR)
      1.03; P = 0.97). Significant determinants of risk included acute vessel closure
      as an indication for stenting (RR = 80.6; P < 0.001) and sex (male: female RR =
      0.19; P = 0.02). The median length of stay (LOS) was 5 days (1-45). Use of a
      linear regression model showed that anticoagulation added 4.5 days and a major
      complication added a further 4.5 days to a baseline length of stay of 3.2 days
      (R2 = 0.32; P < 0.001). CONCLUSION: This is a report of coronary stenting as part
      of usual clinical practice in one British tertiary referral centre. In this
      experience, treatment with aspirin alone is probably as safe as intensive
      anticoagulation, and has the benefit of reducing length of stay by more than 50%
      to 3.2 days in an uncomplicated case.

PMID- 8868981
TI  - Plasma cardiac natriuretic peptide determination as a screening test for the
      detection of patients with mild left ventricular impairment.
AB  - OBJECTIVE: To determine the usefulness of measuring the cardiac natriuretic
      peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor,
      and brain natriuretic peptide, as screening tests for identifying patients with
      mild left ventricular impairment. DESIGN: Cross-sectional evaluation of the
      diagnostic accuracy of the cardiac natriuretic peptides. SETTING: Cardiac
      catheterisation unit, Norwegian central hospital. PATIENTS: A consecutive series
      of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One
      hundred and twenty eight of these patients had a history of previous myocardial
      infarction. MAIN OUTCOME MEASURES: The presence of normal and impaired left
      ventricular function, as evaluated by logistic regression analysis and estimation
      of the area under the receiver operating characteristic (ROC) curve (an index of
      overall diagnostic accuracy). Ventricular function was assessed by the
      measurement of left ventricular end diastolic pressure and angiographically
      determined left ventricular ejection fraction. RESULTS: Logistic regression
      analysis showed that plasma brain natriuretic peptide was the best predictor of
      increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001),
      decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the
      combination of left ventricular ejection fraction < or = 45% and left ventricular
      end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC
      function for the detection of left ventricular dysfunction were 0.789 for brain
      natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N
      terminal pro-atrial natriuretic factor. CONCLUSIONS: Plasma brain natriuretic
      peptide seemed to be a better indicator of left ventricular function than plasma
      atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However,
      the overall diagnostic accuracy of circulating atrial natriuretic factor, N
      terminal pro-atrial natriuretic factor, and brain natriuretic peptide as
      indicators of normal and impaired ventricular function in an unselected group of
      patients with coronary heart disease and a high frequency of previous myocardial
      infarction was relatively modest.

PMID- 8868983
TI  - Ball thrombus in the left ventricle.

PMID- 8868984
TI  - Serological and molecular evidence of enterovirus infection in patients with end
      stage dilated cardiomyopathy.
AB  - OBJECTIVE: To study the relative diagnostic value of enterovirus-specific
      molecular biological and serological assays in patients with end-stage dilated
      cardiomyopathy, and to investigate the possible role of other cardiotropic
      viruses in dilated cardiomyopathy. DESIGN: Analysis of recipient myocardial
      tissue and serum from patients with dilated cardiomyopathy and controls
      undergoing cardiac transplantation for end-stage cardiac disease. SETTING:
      University virology department and transplantation unit. METHODS: Reverse
      transcriptase-polymerase chain reaction and nucleotide sequence analysis of
      myocardial RNA and DNA; enterovirus-specific in situ hybridization; enterovirus
      specific immunoglobulin M detection. RESULTS: Enterovirus RNA was detected in
      myocardial tissue from only a small proportion of (five of 75) hearts. However,
      although enterovirus-specific immunoglobulin M responses were detected in 22
      (28%) of 39 controls patients, a significantly higher prevalence was observed
      among patients with dilated cardiomyopathy (22 (56%) of 39 patients; P < 0.005).
      All enteroviruses detected in myocardium showed greatest nucleotide sequence
      homology with coxsackievirus type B3. Detection of enterovirus RNA in myocardium
      by the polymerase chain reaction and by in situ hybridisation gave comparable
      results. Other potentially cardiotropic virus genomes, including human
      cytomegalovirus, influenzaviruses, and coronaviruses were not detected in
      myocardium. CONCLUSION: This study found that enterovirus-specific immunoglobulin
      M responses provided the strongest evidence of enterovirus involvement in
      patients with end-stage dilated cardiomyopathy. However, the high background
      prevalence of these responses limits their diagnostic value. The finding that
      enteroviruses detected in myocardium were coxsackievirus type B3 accords with
      recent findings in patients with acute myocarditis, and indicates that this
      serotype is the major cardiotropic human enterovirus.

PMID- 8868985
TI  - Severe aortic stenosis without left ventricular hypertrophy: prevalence,
      predictors, and short-term follow up after aortic valve replacement.
AB  - OBJECTIVES: The purpose of the present study in patients with severe aortic
      stenosis was to assess the prevalence of absent left ventricular hypertrophy
      (LVH) (determined according to mass criteria), to identify predictors of absent
      LVH, and to assess short-term left ventricular adaptation and prognosis after
      aortic valve replacement. METHODS: Left ventricular mass (LVM) was determined by
      echocardiography in 109 men and 101 women with severe aortic stenosis (mean
      pressure gradient < or = 50 mm Hg). LVH was defined as LVM > or = 109 g/m2 in
      women and LVM > or = 134 g/m2 in men. RESULTS: One hundred and eighty nine
      patients showed LVH (group 1) (90%; mean (SD) age 65 (14) years), and 21 showed
      no LVH (group 2) (10%, age 57 (21) years P = 0.02 for difference in age). Twelve
      (6%) of those without LVH had increased relative wall thickness (that is, > or =
      0.45 with LV concentric remodelling) and nine (4%) showed no macroscopically
      detectable hypertrophic adaptation. The following variables were associated with
      the absence of LVH: low body surface area, low body mass index, and increased
      cardiac index. 76/210 patients were followed up a mean of six months after aortic
      valve replacement. The frequency of adequate ventricular adaptation to the
      decreased afterload after aortic valve replacement was higher in patients with
      LVH than in those without. Mortality six months after aortic valve replacement
      was lower, but not significantly, in patients with LVH (7.6%) than in those
      without LVH (12.5%, P = 0.10). CONCLUSIONS: A tenth of patients with severe
      aortic stenosis did not develop LVH according to mass criteria; 4% of the
      patients did not have any macroscopic signs of myocardial adaptation to the
      pressure overload despite longstanding disease. Small body size was independently
      associated with lack of LVH according to mass criteria. Six months after aortic
      valve replacement, ventricular adaptation was more often adequate in patients
      with LVH than in those without.

PMID- 8868986
TI  - Evaluation by electron beam computed tomography of intracardiac masses suspected
      by transoesophageal echocardiography.
AB  - OBJECTIVES: To assess the suitability of electron beam computed tomography (EBT)
      in evaluating and subsequently managing cardiac masses suspected as a result of
      examination by transthoracic and transoesophageal cross sectional
      echocardiography. DESIGN AND PATIENTS: In 76 consecutive patients with suspected
      cardiac masses, the impact of the EBT examination was analysed by reviewing
      whether EBT examination altered management by confirming or excluding a mass,
      whether EBT imaging substantially contributed to decision-making, and lastly
      whether EBT influenced the decision to operate on the patient. RESULTS: EBT
      modified the diagnosis or confirmed results which had been questionable with
      cross sectional echocardiography in 53 cases (70%): these cases included those
      with anatomical features such as dense calcifications or fatty structures (n =
      20), lipomatous lesions (n = 5), equivocal thrombi (n = 5), pericardial masses (n
      = 5), or hydatid cysts (n = 2). EBT gave information over and above cross
      sectional echocardiography in all patients with malignant tumours (n = 16) by
      providing a better delineation of the relation between intracavity masses and
      normal structures, including the mural site of tumour attachment and tumour
      extension to the great vessels and the adjacent extracardiac mediastinal
      structures. EBT provided no additional information over cross sectional
      echocardiography in the remaining patients (n = 23), particularly in those with
      myxomas (n = 11) or small valvar lesions (n = 6). EBT only confirmed that the
      lesion was well demarcated, limited in extent, or not associated with a mass.
      CONCLUSIONS: EBT has considerable potential for clinical management and surgical
      planning and may help clinicians to decide against surgery, particularly in
      patients with unresectable tumours.

PMID- 8868987
TI  - Prophylactic replacement of Bjork-Shiley convexo-concave heart valves: an easy-to
      use tool to aid decision-making in individual patients.
AB  - OBJECTIVE: To develop an easy-to-use tool for decision-making on prophylactic
      replacement of Bjork-Shiley convexo-concave heart valves. DESIGN: Decision
      analysis comparing elective replacement with observation. SETTING: Referral
      centres for patients with artificial heart valves. PATIENTS: Quantitative
      estimates were obtained from a follow up study conducted in The Netherlands,
      including 2303 patients with a mean follow up of 6.6 years and from recently
      published studies. INTERVENTION: Elective valve replacement with a new artificial
      heart valve. MAIN OUTCOME MEASURE: Loss of life-expectancy. RESULTS: A simple
      graph was constructed to present the loss of life-expectancy caused by strut
      fracture for combinations of basal life-expectancy (life-expectancy without strut
      fracture) and lethal fracture risk (strut fracture risk multiplied by lethality
      of fracture). This loss can be compared directly with the loss of life-expectancy
      caused by surgical mortality. This quantitative approach takes into account
      individual patient characteristics, such as age, gender, cardiac comorbidity, and
      position of the valve, but the final estimation of surgical mortality also
      requires clinical judgement. The calculations can be made easily by hand or with
      a simple computer application. CONCLUSIONS: This decision support tool enables
      the direct estimation of the gain or loss of life-expectancy that is likely with
      replacement of a Bjork-Shiley convexo-concave heart valve. It can be used to
      evaluate individual patients as well as groups of patients, and allows for easy
      incorporation of revisions of fracture risk estimates.

PMID- 8868988
TI  - Transcatheter occlusion of the arterial duct with Cook detachable coils: early
      experience.
AB  - OBJECTIVE: To assess the effectiveness of modified, controlled release Gianturco
      coils for transcatheter occlusion of the arterial duct. DESIGN: Prospective
      study, approved by local medical ethics committee. SETTING: Tertiary paediatric
      cardiac centre. PATIENTS: 43 patients with left to right shunting through the
      arterial duct, two of whom had a residual leak after surgical ligation and three
      had residual shunting after previous Rashkind umbrella implantation.
      INTERVENTION: Transcatheter delivery of one or more coils to the arterial duct.
      MAIN OUTCOME MEASURES: Complete occlusion of the arterial duct, based on
      intention to treat and judged by Doppler echocardiography. Absence of flow
      disturbance in the branch pulmonary arteries and the descending aorta following
      the procedure. Assessment of cost of the disposable items used. RESULTS: At a
      median follow up period of three months complete duct occlusion was achieved in
      37 (86%) of the 43 patients. No flow disturbance in the branch pulmonary arteries
      or the descending aorta was detected in any patient. The median cost of
      disposable items used during the procedure was 342 pounds. CONCLUSIONS: The Cook
      detachable coil is an effective and financially attractive alternative to the
      Rashkind umbrella for closure of the arterial duct.

PMID- 8868989
TI  - Long-term fate of the coronary arteries after the arterial switch operation in
      newborns with transposition of the great arteries.
AB  - OBJECTIVE: Concern continues to be expressed about the long-term impact of
      coronary artery translocation after the arterial switch operation for
      transposition of the great arteries. This study was conducted to determine the
      prevalence of obstructions of the translocated coronary arteries by the use of
      selective coronary artery angiography. METHODS AND RESULTS: 64 children (mean age
      7.6 (SD) 1.5 years) who had survived an arterial switch operation underwent
      evaluation. They had been operated on by one surgeon and they were followed up by
      a single hospital. Selective coronary artery angiography was possible in 58
      patients. Five patients showed occlusion or stenosis of a coronary artery: one
      occlusion and two stenoses of the left coronary trunk, two occlusions of the
      circumflex artery. The prevalence of late coronary artery complications was 7.8
      (SD) 6.6% (95% CI 1.2 to -14.4%). The three patients with occlusion of one
      coronary artery had perioperative ischaemic complications, with associated
      electrocardiogram evidence of ischaemia and left ventricular dysfunction with
      mitral valve insufficiency. Both patients with stenosis of the left main coronary
      artery trunk did not have any evidence of an anomaly before catheterisation.
      CONCLUSIONS: The prevalence of the late coronary artery complications after an
      arterial switch operation was low in this series. This accords with the view that
      the arterial switch operation remains the preferred treatment for such patients.
      Screening for late coronary artery patency should be done by using selective
      coronary artery angiography, because even patients who remain symptom free can
      have coronary artery anomalies.

PMID- 8868991
TI  - Thrombus in a normal sinus of Valsalva: angiographic, multiplane transoesophageal
      echocardiographic, and surgical findings.
AB  - A large intraluminal thrombus within an otherwise normal sinus of Valsalva was
      diagnosed in a 41 year old man who was investigated for myocardial infarction.
      The thrombus was suspected by aortic root injection, confirmed by
      transoesophageal echocardiography, and treated surgically.

PMID- 8868990
TI  - Ventricular myoarchitecture in tetralogy of Fallot.
AB  - BACKGROUND: Little attention has been paid to the architecture of the muscle
      fibres of the ventricular walls in congenitally malformed hearts. In this study
      the gross pattern of myocardial fibres in normal hearts was compared with that in
      cases of tetralogy of Fallot. METHODS AND RESULTS: After morphological
      examination nine specimens with tetralogy were dissected to study the ventricular
      myoarchitecture. Changes were found in the shape of the malformed ventricles. The
      ventricular walls were arranged in layers in all hearts. Superficial and deep
      layers were present in both ventricles, with the superficial layer showing a more
      oblique orientation in the specimens with tetralogy than in normal hearts.
      Modifications of muscle fibre that were related to the type of malformation were
      seen in the deep layer. A middle layer was present in the left ventricles of
      normal hearts and specimens with tetralogy: this showed a horizontal orientation
      in both groups. In contrast, a middle layer was found in the right ventricle only
      in specimens showing tetralogy. CONCLUSIONS: The malformed hearts showed
      modifications in ventricular shape, in the arrangement of muscle in the right
      ventricle, and in the overall myoarchitecture. These changes could well be the
      consequence of the same agent (or agents) that caused the structural defect.

PMID- 8868992
TI  - Temporary decrease in heart rate in Lyme carditis during treatment with
      antibiotics.
AB  - Lyme disease is a recognised cause of atrioventricular block. In most cases the
      conduction disturbances are reversed by treatment with antibiotics. A 44 year old
      man with third degree atrioventricular block in Lyme carditis had a temporary
      decrease in heart rate during resolution of the heart block two days after
      treatment with antibiotics was started.

PMID- 8868994
TI  - Catheter ablation for successful management of left posterior fascicular
      tachycardia: an approach guided by recording of fascicular potentials.

PMID- 8868993
TI  - Evaluation of mortality and morbidity during four years after late thrombolysis
      in acute myocardial infarct.

PMID- 8868995
TI  - Is thrombolytic therapy really better than conventional treatment in acute
      inferior myocardial infarct.

PMID- 8868996
TI  - Distress correlates with degree of chest pain: a description of patients awaiting
      revascularisation.

PMID- 8868997
TI  - Molecular biology and molecular genetics of nitric oxide synthase genes.

PMID- 8868998
TI  - Endothelin-1 produces heterogeneous regional haemodynamic effects in conscious
      rabbits.
AB  - Blood flow in the renal artery, superior mesenteric artery and infra-renal
      abdominal aorta of conscious rabbits was measured by Doppler ultrasound. Arterial
      pressure, heart rate and blood flow responses were assessed following 0.2 and 0.8
      nmol/kg intravenous endothelin-1. The effects of the following antagonists on
      these responses were examined: phentolamine, propranolol, scopolamine, captopril,
      nifedipine, indomethacin, the V1-vasopressin receptor antagonist
      d(CH2)5Tyr(Me)AVP and the competitive nitric oxide (NO) synthase inhibitor NG
      nitro L-arginine (NOLA). Hindlimb resistance and arterial pressure responded in
      two phases, initial vasodilatation followed by vasoconstriction. Renal and
      mesenteric vasoconstriction occurred without initial vasodilatation. Following
      0.2 nmol/kg endothelin-1, arterial pressure decreased by 18.5 +/- 0.8 mmHg, then
      increased by 25.2 +/- 1.7 mmHg (n = 27). Heart rate changed reciprocally. Renal
      resistance increased by 533 +/- 73% (n = 12). Mesenteric resistance increased by
      420 +/- 34%. Hindlimb resistance decreased 54 +/- 2% (n = 12, all P < 0.01) then
      increased slightly (P < 0.05). All changes were greater at 0.8 nmol/kg,
      particularly the hindlimb vasoconstriction. The only antagonist to alter
      significantly these responses was NOLA, which in the hindlimb attenuated the
      vasodilatation and accentuated the vasoconstriction. We conclude that most of the
      haemodynamic effects of endothelin-1 are direct, but that NO generated by NO
      synthase causes part of the hindlimb vasodilatation, and that endothelin-1
      induced vasoconstriction is attenuated by release of NO.

PMID- 8868999
TI  - Effect of ifetroban, a thromboxane A2 receptor antagonist, in stroke-prone
      spontaneously hypertensive rats.
AB  - Experiments were performed to determine the effect of chronic therapy with the
      potent and long-acting thromboxane (TX) A2/prostaglandin endoperoxide (TP)
      receptor antagonist, ifetroban, on hypertension development and the incidence of
      stroke in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP
      instrumented with radiotelemetry probes, for continuous monitoring of arterial
      blood pressure, were given 1% NaCl to drink and Stroke-Prone Rodent Diet and were
      chronically treated with ifetroban (20 mg/kg/day, n = 10) or vehicle (n = 12)
      starting at 16.5 weeks of age. Ifetroban did not affect blood pressure or the
      development of proteinuria and cerebrovascular lesions. Chronic administration of
      a higher dose ifetroban (40 mg/kg/day) starting at 7 weeks of age was also
      without effect on blood pressure and stroke in noninstrumented saline-drinking
      SHRSP. These results do not support a major role for TXA2 and its endoperoxide
      precursors in the elevation of blood pressure and the development of
      cerebrovascular lesions in saline-drinking SHRSP.

PMID- 8869000
TI  - Nonpeptide angiotensin II receptor antagonists: in vivo inhibition of [125I
      Sar1,Ile8]angiotensin II binding by losartan, EXP597 and L-159,282 in rats.
AB  - Effects of losartan, L-159,282 and EXP597 on the in vivo binding of [125I
      Sar1,Ile8]angiotensin II to kidney cortex and adrenal were examined in rats.
      Losartan, an AT1 receptor antagonist, completely blocked [125I
      Sar1,Ile8]angiotensin II binding to the kidney cortex which contains only AT1
      binding sites with an ID50 of 0.06 mg/kg. Losartan partially inhibited [125I
      Sar1,Ile8]angiotensin II binding to the adrenal which contains equal amounts of
      AT1 and AT2 binding sites. Blockade by the AT1 receptor antagonist L-159,282
      sufficiently increased the plasma levels of angiotensin II to block the AT2
      receptor. EXP597 inhibited [125I-Sar1,Ile8]angiotensin II binding to the kidney
      cortex and adrenal almost totally with ID50s of 0.05 and 0.06 mg/kg,
      respectively. This result suggests that EXP597 exhibits almost equal binding
      affinity for AT1 and AT2 binding sites in vivo in rats.

PMID- 8869001
TI  - Effects of early captopril treatment and its removal on plasma angiotensin
      converting enzyme (ACE) activity and arginine vasopressin in hypertensive rats
      (SHR) and normotensive rats (WKY).
AB  - The purpose of this study was to evaluate the effects of early administration and
      removal of the ACE inhibitor, captopril (CAP) on the plasma ACE activity, AVP
      levels, and mean arterial pressure (MAP) in groups of rats, control and CAP
      treated SHR and WKY (SHR, WKY SHRCAP, WKYCAP, respectively and in SHR taken off
      CAP (OFFCAP) and their progeny (2nd generation, 2ndG). Plasma ACE activity in
      SHRCAP (54.8 +/- 2.1 mU/ml/min) was significantly greater than in SHR (25.96 +/-
      0.34 mU/ml/min) and their offspring (OFFCAP, 26.32 +/- 2.71 and 2ndG, 17.62 +/-
      2.47 mU/ml/min, P < 0.001, respectively). Plasma level of AVP in SHR (14.18 +/-
      0.98 pg/ml) were greater than in SHRCAP (9.1 +/- 1.01 pg/ml, P < 0.01). A
      decrease in plasma AVP levels were also noted in OFFCAP (10.48 +/- 0.51 pg/ml)
      and their offspring 2ndG (10.34 +/- 0.46 pg/ml). Our results did not show a
      relationship between plasma ACE activity and blood pressure reduction. However,
      treatment of SHR with captopril produced a decrease in plasma AVP levels which
      may participate in its antihypertensive mechanism of action.

PMID- 8869002
TI  - Vascular reactivity to phenylephrine and angiotensin II in hypertensive rats
      associated with insulin resistance.
AB  - Previous reports suggest that when rats are fed a carbohydrate-enriched diet they
      develop hyperinsulinemia associated with elevated blood pressure. The purpose of
      this study was to assess the vascular reactivity of fructose-treated rats to
      various pressor agents. Male Sprague Dawley rats (n = 24) were used for this
      study and were divided into two equal groups. One of the groups was fed normal
      rat chow and served as the control group, whereas the other group was fed a
      fructose-enriched diet for four weeks. Mean blood pressure was elevated in the
      fructose-treated rats at the end of the second week of fructose treatment and
      remained elevated for the remainder of the study. At the end of the second and
      fourth weeks of fructose treatment, six rats from each group were used to assess
      both in vivo and subsequently in vitro vascular reactivity to various pressor
      agents. The jugular vein and carotid artery were cannulated under anesthesia.
      Twenty four hours after recovery from surgery pressor responses to angiotensin II
      (AII) and phenylephrine (PE) were determined. Twenty four hours later rats were
      decapitated and the thoracic aorta was removed, cleaned of adhering fat and cut
      into ring segments for vascular reactivity studies. Tissues were suspended in
      muscle baths containing physiological saline solution and maintained at 37
      degrees C. Dose-response curves were generated in the aorta in response to
      potassium chloride (KCl), AII and PE. At the end of the second week of fructose
      treatment pressor response to AII was significantly increased in the fructose
      treated rats compared to the controls whereas there was no significant difference
      in pressor response to PE. There was no significant difference in pressor
      response to AII and PE between the two groups at the end of the fourth week of
      fructose treatment. In vitro contractile response of the aorta to AII and PE were
      significantly greater in the fructose-fed rats compared to the controls at the
      end of the second week of fructose treatment; however, there was no change in the
      EC50 between the two groups. At the end of the fourth week of fructose treatment,
      the contractile responses to AII and PE were similar in both groups, although the
      response to AII tended to be lower in the fructose-fed rat. There was no
      significant difference in the contractile response to potassium chloride or in
      acetylcholine-induced relaxation throughout the study. These results strongly
      suggest that hypertension in fructose-treated rats is associated with increased
      in vitro vascular reactivity to AII and PE in the early stages of hypertension.

PMID- 8869003
TI  - Does combined therapy of Ca-channel blocker and angiotensin converting enzyme
      inhibitor exceed monotherapy in renal protection against hypertensive injury in
      rats?
AB  - Either calcium channel blocker (CCB) or angiotensin converting enzyme inhibitor
      (ACEi) is used as an antihypertensive agent, and we are recommended to use them
      in combination to refractory hypertension with evidence dependent on clinical
      observations. We examined the renal protective effect of the combined therapy
      with calcium channel blocker (amlodipine) and angiotensin converting enzyme
      inhibitor (enalapril) against hypertensive renal injury in 5/6 nephrectomized
      spontaneously hypertensive rats (SHRs) with salt loading, comparing with
      monotherapy of each drug. Forty males SHRs with 5/6 nephrectomy and salt loading
      were divided to five groups: group 1 as control (n = 8), group 2 received 0.2
      mg/kg/day of amlodipine (n = 8), group 3 received 0.2 mg/kg/day of enalapril (n =
      8), group 4 (n = 8) and group 5 (n = 8) that were treated with 0.1 mg/kg/day and
      0.2 mg/kg/day of each drug in combination respectively. Either amlodipine or
      enalapril had remarkable effects on reducing the increases in blood pressure and
      urinary protein excretion. In histopathological examination, it also suppressed
      renal injury significantly. Additional significant effect of combined therapy was
      not observed in blood pressure and urinary protein. There were not remarkable,
      additional effects of the combination of CCB and ACEi on protecting the remnant
      kidney in 5/6 nephrectomized SHRs fed a high-salt diet, possibly because sodium
      retention was not alleviated by the combination.

PMID- 8869004
TI  - The mechanisms of the improvement of insulin sensitivity by angiotensin
      converting enzyme inhibitor.
AB  - To investigate the role of kinins in augmentation of insulin sensitivity by
      angiotensin converting enzyme inhibitor (ACEI), the effects of ACEI (delapril) on
      the insulin resistance in fructose-fed rats (FFR) were evaluated with or without
      the administration of bradykinin receptor antagonist (Hoe 140). Male Sprague
      Dawley rats were fed on fructose rich chow (FFR) or standard chow (control) for 4
      weeks and treated with 10 mg/kg/day of delapril with or without Hoe 140 (0.5
      mg/kg/day) for an additional 2 weeks. Steady state plasma glucose (SSPG) and
      steady state plasma insulin (SSPI) were determined while the rats were conscious.
      Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to
      determine insulin sensitivity in each group. Mean blood pressure (MBP), SSPG and
      SSPI were significantly higher in FFR than in control, and were significantly
      lower in the FFR+delapril than in FFR+vehicle. There were no difference in MBP,
      SSPG and SSPI between FFR+delapril+vehicle and FFR+delapril+Hoe 140. We concluded
      that the main mechanisms of improving the insulin sensitivity by ACEI may not be
      the enhancement of kinins but the suppression of angiotensin II in FFR.

PMID- 8869005
TI  - The prevalence of diabetic complication of elderly diabetics in Himeji.
AB  - Diabetes mellitus has recently markedly increased among elderly patient's
      diseases. There are no recent epidemiological reports on the relative number of
      male and female diabetic patients. So, an epidemiological study was performed on
      746 Non-Insulin-Dependent Diabetes Mellitus patients, whose data were obtained
      from members of the Himeji Internal Medicine Association, divided into six groups
      according to sex and duration of illness. The following results were obtained. 1)
      The number of male patients was greater by about 20% than that of female
      patients, while elderly patients accounted for a larger proportion, nd age at
      onset of disease was about ten years higher in female than in male patients. 2)
      All indicators of diabetes mellitus became worse with longer duration of illness.
      3) There was a correlation between the prevalence of complications and the
      duration of illness: The prevalence of complications increased in parallel with
      increasing duration of illness, and this tendency was more marked in female than
      in male patients. 4) Female patients had a more marked tendency to develop
      hypertension, hyperlipidemia and obesity than male patients. 5) Microangiopathy
      generally manifested itself earlier than macroangiopathy, and the increase in the
      prevalence of angiopathy in accordance with prolonged duration of illness was
      more marked for microangiopathy than for macroangiopathy. Clinical features of
      Japanese diabetics are found to be similar to those of Europeans, especially
      dominant in females. This might be due to the changing life style in japan.

PMID- 8869006
TI  - The effect of extraction methods. The kind of organ samples and the examination
      delay on the DNA yields and typing.
AB  - This study investigated the effect of DNA extraction methods, examination delay
      and the kind of organs samples to the DNA yields and typing. Thirty autopsy cases
      with postmortem period less than 12 hours were used as the sample resources. The
      DNA was successfully extracted from cerebral cortex, liver, spleen, lymph nodes,
      kidney, psoas muscle and prostate gland by Bar and Kirby methods. The
      spectrophotometric measurement showed that the spleen, lymph nodes, kidney and
      liver provided more DNA rather than the other organs. The agarose gel
      electrophoresis showed that the majority of the samples had High Molecular Weight
      DNA (HMW-DNA) with variable degree of degradation. All of these DNA were
      successfully typed on the D1S80 locus using the PCR according to Kasai method.
      The spleen samples were collected from the same cases and stored at -20 degrees C
      for 1 to 6 weeks before the DNA extraction was performed. The analysis of the DNA
      extracted from these samples showed that the DNA yields and typing did not change
      significantly among the samples with examination delay up to 6 weeks after the
      sample collection. The comparison between the Bar and Kirby methods showed that
      the Kirby method resulted in more DNA yields with the same purity of DNA, but
      less HMW-DNA compared with Bar method.

PMID- 8869007
TI  - Projections from the lateral mammillary nucleus to the anterodorsal thalamic
      nucleus in the rat.
AB  - There has been an abundance of research on the connections of the mammillary
      bodies but the projections from the lateral mammillary nucleus to the
      anterodorsal thalamic nucleus has remained a gray area due to a dearth of
      material which directly addresses the details of this pathway. This study seeks
      to further define the nature of this particular nerve connection within the
      mammillothalmic tract. The technique employed is fluorescent nerve tract tracing
      using two fluorescent tracers implanted separately into each anterodorsal
      thalamic nucleus then followed retrogradely to the soma of the neurons in the
      lateral mammillary nucleus. Fluorescent photomicrography allowed us to document
      the single and double labeled cells of the lateral mammillary nucleus. The single
      labeled cells can be categorized into ipsilaterally projecting neurons and
      contralaterally projecting neurons. About half of all labeled cells were
      bilaterally projecting double-labeled, a third was ipsilaterally projecting
      single-labeled and the remainder were contralaterally projecting single labeled
      cells. There were no labeled cells traced to the medial mamillary nucleus. The
      mammillary bodies play an important role in the limbic circuitry and a part of
      the so-called "Papez Circuit". The pathway by which the mammillary body projects
      to the other structures of the limbic system and the way it connects the limbic
      system to other parts of the brain like the tegmentum is not fully understood.
      This clarification of the connection between the lateral mammilary nucleus and
      the anterodorsal thalamic nucleus is but one of the contemplated pathways.

PMID- 8869008
TI  - Bifurcating projections from the retinal ganglion cells to the primary visual
      targets (SC and LGN) in the cat.
AB  - Bifurcating projections of retinal ganglion cells to the primary visual targets
      were studied in the cat using a retrograde fluorescent double-labeling technique
      with Fluoro-Gold (FG) and Evans Blue (EB) as the tracers. Following injections of
      FG and EB into the left and right lateral geniculate nuclei (LGN), or into the
      left and right superior colliculi (SC), or LGN and SC on the same side, 4.56% of
      the single-labeled cells with one tracer were simultaneously labeled by the other
      tracer injected contralaterally in bilateral LGN-injection group; 12.18% of the
      single-labeled cells were further labeled by the other tracer injected
      contralaterally in bilateral SC injection-group; and 8.95% of the single-labeled
      cells in the ipsilateral retina, 10.94% of the single-labeled cells in the
      contralateral retina by the tracer injected into the LGN were labeled by the
      other tracer injected into the SC on the same side. All three retinal ganglion
      cell classes by size demonstrated double-labeled cell bodies. In the bilateral
      LGN- and bilateral SC-injection groups, the double-labeled cells were mainly of
      the small type (65% and 82.8%, respectively), while in the group of the
      injections into the LGN and SC on the same side, double-labeled cells were
      predominantly of the large type (55.45%). These results indicate that single
      ganglion cells of the retina send bifurcated projections to the bilateral LGN,
      bilateral SC, or unilateral LGN and SC, via axonal collaterals. These bifurcated
      axons can be regarded as an important way by which the information of the single
      ganglion cells can be conducted to the same primary visual targets on both sides,
      and two different optic centers on the same side of the brain.

PMID- 8869009
TI  - Docosahexaenoic acid ethyl ester and its ultraviolet degradation products showed
      DNA-breaking activity in vitro and cytotoxic effects on the HSC-4 cell line.
AB  - The DNA-breaking activity and cytotoxicity of docosahexaenoic acid ethyl ester
      (DHAE) and its degradation products (dDHAE) induced by ultraviolet (UV)
      irradiation, were demonstrated in this study. The major component of dDHAE was
      identified as 4-hydroxyvaleric acid ethyl ester. DHAE and dHAE solutions at a
      concentration of 100 mg/ml induced single-strand breaks of plasmid DNA after an
      incubation at 37 degrees C and pH 7.6 for 15 hours. DHAE transformed a plasmid
      supercoiled DNA (Form I) into an open circular relaxed form (Form II), and dDHAE
      completely destroyed DNA molecules. HSC-4 cells, which were derived from human
      prickle cell carcinoma, were cultured with various concentrations (10, 30 and 50
      micrograms/ml) of DHAE and dDHAE. Both inhibited the proliferation of HSC-4
      cells. The potency of their cytotoxicity was dependent on their concentration. It
      is noteworthy that the lethal effects of DHAE and dDHAE on HSC-4 cells were quite
      similar, although the DNA-breaking activity of dDHAE was much greater than that
      of DHAE. These results suggested that DHAE becomes more cytotoxic after
      undergoing oxidization and metabolism in the cell.

PMID- 8869011
TI  - Acute coronary thrombosis--the role of plaque disruption and its initiation and
      prevention.
AB  - A major factor invoking coronary thrombosis is disruption of an atherosclerotic
      plaque. Studies comparing intact and disrupted plaques have been used to define
      the characteristics of vulnerable plaques i.e. those at risk of disruption. The
      characteristics are a lipid core occupying over 50% of overall plaque volume, a
      thin plaque cap, a large absolute number and density of macrophages, and a
      reduction in the smooth muscle content of the plaque. Such vulnerable plaques
      make up a small proportion of all the plaques present in most individuals.
      Angiographic stenosis, however, does not predict vulnerability because there is
      no relation between core size or plaque size with stenosis. A large proportion of
      disruption episodes go unnoticed clinically because the thrombus does not
      sufficiently encroach on the lumen to cause ischaemia. These subclinical
      episodes, however, will invoke plaque growth. Plaque disruption is followed by a
      smooth muscle proliferative repair response analogous to that occurring after
      angioplasty. In both situations, exuberant repair leads to post event stenosis.
      Reconstruction of coronary lesions at autopsy shows that 70% of high grade
      stenosis (angiographic > 50% diameter) have had an episode of healed disruption.
      Such data highlight the role of plaque disruption in the generation of advanced
      stenotic lesions irrespective of whether an acute clinical event occurred. Any
      therapeutic intervention which increases plaque stability, i.e. resistance to
      disruption, would reduce the acute ischaemic event rate but also slow the
      generation of new high grade stenoses.

PMID- 8869010
TI  - Afferent projections to the cingulate cortex in albino rats: a study with a
      retrograde labeling method using fluoro-gold.
AB  - We studied the neuronal populations that project their axons to the cingulate
      cortex in albino rats using the retrograde fluorescent dye of 4% Fluoro-Gold
      injected into the anterior, middle and posterior portions of the cingulate
      cortex. The result showed that the following ipsilateral structures are sending
      fibers to these three portions: the prefrontal cortex, frontoparietal motor
      cortex, indusium griseum, dorsal endopiriform nucleus, lateral part of medial
      mammillary nucleus, nuclei of diagonal band of Broca, anterior pretectum,
      anterior part of caudate-putamen, hippocampal formation, anteroventral,
      anteromedial, lateroposterior, ventroposterior and dorsomedial thalamic nuclei.
      The anterior portion of the cingulate cortex receives inputs from the following
      ipsi- and contralateral structures: the accessory olfactory bulbs, anterior
      olfactory nuclei, middle and posterior portions of the cingulate cortex. The
      middle cingulate cortex receives fibers only from the ipsilateral dorsal part of
      the lateral septal nucleus in addition from the ipsi- and contralateral anterior
      and posterior portions of the cingulate cortex. While the posterior portion of
      the cingulate cortex receives separate inputs from the following ipsilateral
      structures: anterodorsal thalamic nucleus, temporal cortex, entorhinal cortex,
      areas 17 and 18, as well as from the ipsi- and contralateral anterior and middle
      portions of the cingulate cortex. The present study shows that the cingulate
      cortex receives various kinds of inputs from the other parts of the brain which
      are involved in emotion, memory, vision and motion, and also suggests that there
      are differences in afferent projections among the anterior, middle and posterior
      portions of the cingulate cortex.

PMID- 8869012
TI  - Coagulation and platelet activation pathways. A review of the key components and
      the way in which these can be manipulated.
AB  - Acute coronary syndromes are caused by thrombotic obstruction of usually diseased
      arteries. The thrombotic plug consists of platelets and fibrin. Until recently
      only three antithrombotic drugs, aspirin, heparin and dicumarol were available
      for the prevention and treatment of acute coronary syndromes. A better
      understanding of the cellular and humoral mechanisms underlying these syndromes
      has broadened the arsenal of antithrombotic drugs dramatically. In this review
      the physiological activation process of platelets and the coagulation cascade are
      discussed. Furthermore, the ways in which these processes can be therapeutically
      manipulated are reviewed.

PMID- 8869013
TI  - The role of platelets in arterial thrombosis and the rationale for blockade of
      platelet GPIIb/IIIa receptors as antithrombotic therapy.
AB  - Platelet aggregation plays a crucial role in ischaemic arterial thrombosis.
      Recent biochemical data indicate that the platelet glycoprotein (GP) IIb/IIIa
      receptor mediates platelet aggregation by binding fibrinogen, von Willebrand
      factor, or other ligands, that can span between platelets. New antiplatelet
      agents that block the binding sites on GPIIb/IIIa are efficacious in arterial
      thrombosis animal models and are now being evaluated in human disease. A
      mouse/human chimeric monoclonal antibody fragment (c7E3 Fab) and agents modelled
      after the arginine-glycine-aspartic acid (RGD) cell binding motif are in
      development. c7E3 Fab showed significant efficacy in reducing ischaemic
      complications after angioplasty in patients at high risk of such complications in
      the EPIC study, and thus has been approved for use in the U.S. and several
      European and Scandinavian countries. These new agents also hold considerable
      promise in the treatment of other thrombotic disorders, including unstable angina
      and myocardial infarction.

PMID- 8869014
TI  - New developments in antiplatelet and antithrombotic therapy.
AB  - Several agents which inhibit platelet aggregation (aspirin, ticlopidine,
      dipyridamole), and anticoagulants (vitamin K antagonists, unfractionated heparin,
      low molecular weight heparins and heparinoids) are in clinical use. The search
      for more effective antiaggregating agents has resulted in the development of
      clopidogrel, a chemical analogue of ticlopidine with minimal bone-marrow
      suppressing effects, thromboxane synthase inhibitors and receptor blockers, and
      antagonists of platelet receptor glycoproteins Ib and IIb/IIIa. In addition there
      is increasing therapeutic experience with chimeric monoclonal antibodies against
      the platelet receptors, glycoprotein IIb/IIIa, and, to a minor extent, with
      synthetic peptides or non-peptide inhibitors against the same receptors. Although
      new anticoagulants have become available, their efficacy has only been tested in
      animal models of thrombosis: tissue factor pathway inhibitor, factor Xa
      inhibitors (recombinant tick anticoagulant peptide, antistasin, natural
      pentasaccharide and DX-9065), recombinant thrombomodulin and recombinant protein
      C have been tested in this manner. Considerable clinical progress has been made
      with direct thrombin inhibitors, such as recombinant hirudin and hirulog which
      appear to be effective antithrombotic agents in patients. There is also clinical
      experience with argatroban, an arginine derivative which is a competitive
      antagonist to thrombin. However, PPACK, a tripeptide synthetic compound which
      irreversibly blocks the active catalytic site of thrombin, has not been
      investigated in the clinical setting.

PMID- 8869015
TI  - Immediate outcome following coronary angioplasty. A contemporary single centre
      audit.
AB  - To study the in-hospital outcome of all coronary angioplasty procedures performed
      in a single centre over a 1 year period, with regard to angiographic success and
      the clinical complications of death, myocardial infarction, emergency coronary
      bypass surgery and abrupt coronary occlusion necessitating reintervention.
      METHODS: One thousand one hundred and thirty-three lesions were treated in 970
      procedures in 799 patients between October 1993 and October 1994. Clinical,
      procedural, angiographic and outcome data were entered into a dedicated computer
      data-base and variables tested with respect to outcome using the chi-square test
      and univariate and multivariate analysis techniques. RESULTS: Angioplasty was
      performed for stable angina in 473 (49%) patients, unstable angina in 410 (42%)
      and 80 procedures were emergency--primary myocardial infarction in 44 (4.5%),
      shock in two, abrupt closure in 34 (3.5%) and other indications in seven
      patients. There were 10 (1.0%) deaths and 71 (7.3%) patient were documented to
      have suffered a myocardial infarction as a result of angioplasty. Nineteen (2.0%)
      patients underwent emergency coronary artery bypass surgery. Age >60 and a type C
      lesion were found to be associated with angiographic failure. The chance of a
      complication was increased if the patient was aged >60 years, suffered unstable
      angina, had an ejection fraction <50%, was treated with a new device or suffered
      a significant dissection. CONCLUSION: Despite refinement in techniques and
      increased experience, coronary angioplasty retains a significant associated
      chance of angiographic failure. The complication rate remains significant and
      there has been little reduction in mortality, infarction and abrupt closure rates
      over the last 15 years. The requirement for emergency coronary artery bypass
      surgery appears to be diminishing with the introduction of improved bail-out
      techniques, in particular intracoronary stenting.

PMID- 8869016
TI  - Description of patients undergoing high risk angioplasty. Analyses of various
      databases.
AB  - As the pharmacological and mechanical management of angioplasty procedures
      advances, the description of risk incurred during and after the procedure becomes
      increasingly important. A variety of measures from different sorts of databases
      have been devised to facilitate this task. Large public databases generally
      include descriptors of overall physical health and are most useful in predicting
      catastrophic outcomes, such as mortality. Data from smaller angiographic
      databases are more useful in providing specific descriptors of more common but
      less catastrophic events, such as abrupt closure, myocardial infarction, and
      emergency coronary artery bypass. Most complications are associated with abrupt
      closure of the vessel dilated. In modern PTCA series, the risk of serious
      ishcaemic complications ranges from as low as 3% to as high as 12.9%. Since the
      inception of angioplasty, it has been observed repeatedly that angiographic
      characteristics of target lesions can predict the likelihood of both success and
      ischaemic complications. It has also become apparent that such clinical factors
      as unstable angina with ST segment changes or recent myocardial infarction also
      play important roles by providing a thrombogenic milieu in which the risk of
      intravascular thrombosis is increased. Although advances in operator skills and
      equipment, as well as new devices have dramatically increased the degree of
      lesion complexity which may be approached with PTCA, the actual characteristics
      which are associated with abrupt closure have undergone little change.

PMID- 8869017
TI  - Antiplatelet therapy in therapy-resistant unstable angina. A pilot study with REO
      PRO (c7E3).
AB  - Patients with unstable angina, refractory to intensive medical therapy, are at
      high risk of developing thrombotic complications, such as myocardial infarction
      and coronary occlusion during coronary angioplasty. As platelet aggregation and
      thrombus formation play an important role in this ongoing ischaemic process, a
      monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) has been designed to
      modify the clinical course and underlying coronary lesion morphology. To evaluate
      whether c7E3 could influence the incidence of complications, we randomized 60
      patients to c7E3 or placebo after initial angiography had demonstrated a culprit
      lesion amenable for angioplasty. All patients exhibited dynamic ECG changes and
      recurrent pain attacks, despite intensive medical therapy. After study drug bolus
      and infusion, angiography was repeated and angioplasty performed. Recurrent
      ischaemia during study drug infusion occurred in nine and 16 patients from the
      c7E3 and placebo groups, respectively (P = 0.06). Major events defined as death,
      myocardial infarction or urgent intervention occurred in one and seven patients,
      respectively (P = 0.03). One patient from the placebo group died as a result of
      recurrent infarction. Resolution of clots was only observed in the c7E3 group,
      combined with improvement in TIMI flow grade in 20% of patients. Quantitative
      angiography showed an improvement in percentage diameter stenosis in the c7E3
      group, which was not observed in the placebo group, although the difference
      between the two treatment groups was not significant. No excess bleeding was
      observed in the treatment group. Thus, c7E3 bolus and infusion, combined with
      heparin and aspirin improved the clinical course, the coronary lesion morphology
      and rheology in patients with unstable angina, refractory to medical treatment.

PMID- 8869018
TI  - An overview of the results of the EPIC trial.
AB  - The Evaluation of 7E3 for the Prevention of Ischaemic Complications (EPIC) trial
      assessed the use of abciximab in the treatment of patients at high risk
      undergoing percutaneous revascularization procedures. Abciximab (c7E3) is a
      chimeric monoclonal antibody targeted to block the glycoprotein IIb/IIIa receptor
      on the surface of the platelet; this receptor is believed to be the final common
      pathway of platelet aggregation. Administered at the time of angioplasty or
      directional coronary atherectomy, abciximab had a beneficial effect in the
      population studied, which included patients considered to be at high risk from
      complications of the procedure, based on the presence of acute or recent
      myocardial infarction, severe unstable angina or adverse coronary morphological
      characteristics. Abciximab reduced the risk of the primary endpoint at 30 days
      (death, myocardial infarction, repeat angioplasty or bypass surgery for recurrent
      ischaemia, balloon pump or stent insertion for ischaemia) by 35%: from 12.8% in
      the placebo group to 8.3% in patients treated with abciximab bolus and infusion.
      This trend was observed as a whole and in each component of the primary endpoint.
      At 6 months follow-up, the effect of the treatment was modestly enhanced beyond
      30 days. A variety of substudies have documented substantial evidence of
      treatment benefit in patients with acute myocardial infarction and unstable
      angina. Non-fatal infarction, observed as beyond that normally expected in other
      studies with directional coronary atherectomy, was not above normal in patients
      treated with abciximab, and there was evidence of a treatment benefit in the
      elderly, although more information would be helpful in patients over the age of
      70. The substantial site-to-site variability indicates that standardization of
      percutaneous revascularization could enhance the benefit of abciximab, while
      reducing bleeding complications.

PMID- 8869019
TI  - Early clinical experience with integrelin, an inhibitor of the platelet
      glycoprotein IIb/IIIa integrin receptor.
AB  - Aggregation of platelets leading to thrombosis is one of the hallmarks of
      unstable angina, acute myocardial infarction, and ischaemic complications
      following coronary angioplasty. Activated platelets bind to fibrinogen through
      the glycoprotein IIb/IIIa integrin receptor. New agents have been developed to
      bind this receptor and thus prevent aggregation of platelets. One such compound
      (integrelin) is a cyclical peptide that has been shown to be a potent inhibitor
      of the glycoprotein IIb/IIIa receptor in man. A number of phase I and phase II
      clinical trials have been completed to evaluate this agent for the indications of
      unstable angina, acute myocardial infarction, as well as an adjunct to coronary
      angioplasty. This article will focus on the clinical investigation of integrelin
      with particular emphasis on its use during angioplasty. It has been consistently
      shown across different trials that integrelin can inhibit between 70% and 95% of
      platelet aggregation responses to 20 mumols of ADP at a variety of dosages used
      in the phase II trials. Preliminaray data also suggest that a more clinically
      unstable patient may require a higher dose of integrelin to cause a near complete
      inhibition of the platelet aggregation response to ADP. Future studies will need
      to explore more definitely the relationship between dose of glycoprotein IIb/IIIa
      receptor blockers and clinical instability.

PMID- 8869020
TI  - Evaluation of recombinant hirudin (CGP 39,393/TMREVASC) in the prevention of
      restenosis after percutaneous transluminal coronary angioplasty. Rationale and
      design of the HELVETICA trial, a multicentre randomized double blind heparin
      controlled study.
AB  - One of the main areas of interest in interventional cardiology is the
      understanding, and ultimate prevention of restenosis after an initially
      successful percutaneous transluminal coronary angioplasty. Restenosis is the
      recurrence of luminal narrowing following angioplasty, and still frustrates the
      late results in the treatment of angina pectoris. Experimental, pathological and
      clinical studies suggest that restenosis may occur via activation of the
      coagulation cascade, platelet activation and thrombus formation. Thrombin itself
      is identified as the most potent platelet activator, and has a pivotal role in
      the coagulation system. Furthermore, thrombin directly mediates smooth muscle
      cell proliferation by stimulating thrombin receptors at the smooth muscle cell
      surface. Thrombus indirectly induces excessive intimal smooth muscle cell
      proliferation by means of released mitogens (growth factors), which may
      contribute to late restenosis. Therefore direct and irreversible thrombin
      blockade by hirudin is deemed to be effective in the prevention of restenosis
      following angioplasty. The HELVETICA trial is a multicentre, randomized, double
      blind heparin-controlled study, designed to compare the effects of two dose
      regimens of recombinant-hirudin (CGP 39,393/TMRevasc) with those of heparin on
      event-free survival, safety, tolerability and luminal renarrowing using
      quantitative coronary angiography no later than 26 weeks after the coronary
      angioplasty procedure.

PMID- 8869021
TI  - Prevention and management of thrombotic complications during coronary
      interventions. Combination therapy with antithrombins, antiplatelets, and/or
      thrombolytics: risks and benefits.
AB  - Acute occlusions after percutaneous transluminal coronary intervention occur in
      about 5% of cases. The incidence of these serious adverse events may be reduced
      by the identification of risk factors, appropriate indication for the
      intervention, and by medical therapy with antiplatelets and antithrombins. The
      medical management of complications during percutaneous transluminal
      interventions also may include thrombolytics. Aspirin has been shown to
      significantly reduce the incidence of procedure-related coronary occlusion and
      ischaemic events. Available data suggest pre-treatment with 250-500 mg followed
      by 100-300 mg aspirin after the intervention. Ticlopidine seems to be equally
      effective; however, because of its side effects it should be used only in cases
      of a contra-indication to aspirin. The second indispensable therapeutic concept
      in the prevention of acute thrombotic events during PTCA is thrombin inhibition.
      The level of anticoagulation achieved by heparin seems to be critically
      important. Therefore the recommendation for heparin dosing is a bolus of 10,000 U
      followed by an intravenous infusion over 24 h of either 1000 U.h-1 or an infusion
      adjusted to keep the aPTT above 3 times control, but lower doses of shorter
      duration may be equally effective in uncomplicated cases. Prolonged pre-treatment
      with heparin may be useful if the pre-intervention angiogram is suggestive of
      intracoronary thrombus. Thrombolysis as an adjunct to PTCA did not reduce the
      rate of periprocedural coronary occlusions, but pre-treatment with thrombolysis
      may be useful in patients with recanalization of occluded vein grafts or in
      patients with large amounts of thrombotic material. In acute coronary occlusion,
      thrombolysis has rarely been used as a sole rescue therapy and results have not
      been encouraging, although a thrombotic process often is involved. Thrombolysis
      as an adjunct to rescue angioplasty showed no better clinical outcome than
      prolonged balloon inflation or stenting. Because of serious bleeding
      complications, thrombolysis should only be considered as a treatment option if
      thrombosis is unequivocally the major cause of the acute occlusion.

PMID- 8869022
TI  - Clinical management of unstable angina: the place of antithrombins and platelet
      GP IIb/IIIa receptor blockers.
AB  - Unstable angina is a clinical and anatomic mosaic in which platelet aggregation,
      thrombus formation and fixed and dynamic coronary artery restrictions play
      variable and changing roles. Emerging medical and mechanical options to deal with
      each of these components show promise. GP IIb/IIIa receptor blockade is a
      significant advance over aspirin as all pathways to platelet aggregation are
      blocked by the new agents. Whether the new antithrombins represent a major
      advance over heparin is less clear as prothrombin activation is not blocked and
      rebound is seen as a result. For these new antiplatelet and antithrombin
      medications, encouragement is based upon small trials. The initial impressions
      need to be confirmed in larger trials before the role of these expensive new
      agents can be defined.

PMID- 8869023
TI  - Bleeding risks, risk factors and management of bleeding complications after
      treatment with anticoagulants, specific antithrombins, thrombolytics IIb-IIIa
      receptor blockers.
AB  - Assessment of the risks of new antithrombotic therapies is best undertaken by
      evaluating risk factors for bleeding in individual patients, and risks associated
      with specific antithrombotic agents. This forms the basis for the development of
      a management strategy for major bleeding complications. Patient-related risk
      factors for bleeding with oral anticoagulants include: trauma, invasive
      procedures, history of bleeding disorder, high anticoagulant intensity,
      concomitant use of antiplatelet drugs, presence of underlying severe disease,
      advanced age, and prior history of cerebrovascular accident, or gastrointestinal
      bleeding. Weight-adjusted and other nomograms are more successful in achieving a
      balance between therapeutic effect and safety with intravenous heparin. The most
      important complication of thrombolytic therapy is intracranial haemorrhage, and
      the risks increase with age > 65 years, weight under 70 k, hypertension on
      admission and the use of tissue plasminogen activator: this profile is helpful in
      assessing risk-benefit ratio amongst individual patients. Recent experience with
      the experimental use of antithrombin agents such as hirudin, indicates a delicate
      dose-response relationship as it relates to the risk of cerebral haemorrhage,
      when used in conjunction with thrombolytic agents. A definitive answer regarding
      the role of hirudin and the balance of safety and efficacy awaits completion of
      ongoing trials. Novel IIb/IIIa platelet inhibitors appear to offer a significant
      therapeutic advance: major bleeding is variable and depends in part on the use of
      concomitant procedures, and heparin therapy. It is important to identify the
      source and severity of bleeding with the use of antithrombotic therapy and its
      haemodynamic consequences in constructing a management plan. Well developed
      treatment algorithms for patients with severe bleeding exist, and although
      laboratory testing may be helpful, it is on balance of marginal benefit since
      patients usually require urgent therapy. Future investigation promises more
      readily available, rapid and specific laboratory testing, and newer
      antithrombotic agents that are easier to administer and monitor. Molecular
      targeting with fusion proteins that attract to a specific antigen, thereby
      delivering more effective and safe therapy, offer new promise.

PMID- 8869024
TI  - Costs and effects of c7E3 in high risk PTCA patients. An indirect analysis for
      The Netherlands.
AB  - A cost effectiveness study is presented on the use of c7E3 in high risk patients
      undergoing percutaneous coronary angioplasty (PTCA). The results from the EPIC
      study have been combined with cost data from The Netherlands. The study took
      account of the number of survivors without ischaemic events, and the number with
      neither ischaemic events nor bleeding (both measured after 6 months). It is
      estimated that the initial costs of c7E3 and the additional costs due to the
      increased risk of bleeding are almost entirely counterbalanced by the savings, as
      a result of fewer myocardial infarctions and revascularizations. The additional
      costs per additional patient without ischaemic events are approximately DFL 5235.
      The additional costs per additional patient with neither ischaemic events nor
      bleeding are estimated at DFL 15,685. Both figures are less than the average for
      similar procedures without c7E3. Sensitivity analysis supports the conclusion
      that c7E3 treatment is efficient. However, cost effectiveness could be further
      improved if patients are carefully selected.

PMID- 8869025
TI  - Intravascular ultrasound: a guide for management of complications during
      intervention?
AB  - Within a few years, intravascular ultrasound (IVUS) has emerged from a research
      tool into an intrinsic part of modern invasive cardiology, mainly because
      histology can be obtained 'in-vivo'. For the first time in invasive cardiology it
      is possible to base decisions not only on lumenograms but also on vessel wall
      assessment. IVUS can be used as both a diagnostic tool and for intervention
      purposes. Its diagnostic strength lies in its ability to monitor compensatory
      coronary artery enlargement as a response to arteriosclerosis, to reveal occult
      left main stem disease, and angiographically 'silent' arteriosclerosis. As
      regards intervention, IVUS aids in optimal device selection, i.e. whether to use
      rotablators in calcified lesions or atherectomy devices in large plaques. The
      effects of PTCA on vessel wall morphology can be studied in great detail and the
      effect on luminal gain assessed almost on-line. Several groups have shown that
      the residual plaque area, even after angiographically successful PTCA, is about
      60%. A significant reduction in this percentage may influence long-term outcome
      after PTCA. Luminal areas that are minimal after PTCA seem to indicate
      restenosis, while morphological appearance on its own seems to be less
      predictive. One answer to the shortcomings of standard PTCA are coronary artery
      stents. Intravascular monitoring of stent expansion led to the deployment of high
      pressure stents with a significant increase in post-procedural luminal diameters,
      and finally the ability to withhold anticoagulation in patients with optimal
      stent deployment. Furthermore, integrated devices, such as balloons on IVUS
      catheters, steerable catheters, integrated flow measurements, pressure
      transducers, and, hopefully, tissue characterization, will further enhance the
      usefulness of IVUS.

PMID- 8869026
TI  - Coronary artery flow monitoring: the value of intravascular Doppler for detection
      of complications after interventions.
AB  - Ultrasound transducer-tipped guidewires can be used for coronary interventions,
      and they permit the monitoring of coronary flow before, during, and after the
      interventions. The flow signal contains valuable information regarding the
      quality and stability of the final result. Restoration of typical phasic flow
      patterns with diastolic predominance is one guide to final result. Monitoring the
      trend in average velocity over several minutes after completion of the procedure
      can detect subtle alterations in flow that may presage abrupt closure. These flow
      alterations might also help predict active plaques with heavy thrombus
      involvement that may undergo recurrence in the weeks and months after successful
      procedures.

PMID- 8869027
TI  - Coronary intervention: risk stratification and management of abrupt coronary
      occlusion.
AB  - Balloon angioplasty is associated with an often unpredictable risk of abrupt
      coronary occlusion, which is the leading cause of in-hospital death and
      myocardial infarction. Clinical, angiographic and lesion variables predictive of
      risk of abrupt occlusion are reviewed and a low, medium and high risk profile
      stratification is developed. Current management of abrupt occlusion is discussed.

PMID- 8869028
TI  - IL-7 upregulates T cell receptor/CD3 expression by cultured dendritic epidermal T
      cells.
AB  - Dendritic epidermal T Cells (DETC) in adult mice express uniformly the phenotype
      of Thy-1+, T cell receptor (TCR)-V gamma 3/V delta 1+, CD3+, CD4- and CD8-. In
      newborn mice, however, the epidermis contains smaller numbers of Thy-1+ cells and
      they rarely express TCR or CD3, suggesting that a phenotypic maturation and/or a
      rapid expansion of TCR+/CD3+ cells must occur within the epidermis soon after
      birth. We have observed previously that keratinocytes produce biologically
      relevant amounts of IL-7 and that this cytokine promotes the survival and growth
      of DETC in vitro. Here we report that IL-7 also promotes CD3/TCR expression by
      DETC. When the long-term cultured DETC line, 7-17, was incubated with IL-7,
      surface expression was upregulated in time- and dose-dependent fashions, as
      assessed with antibodies against gamma delta TCR, V gamma 3 TCR or CD3 epsilon.
      Among 10 other cytokines tested, only IL-2 was effective. IL-7-dependent
      upregulation also occurred at the levels of mRNA expression (Northern blot) and
      protein synthesis (immunoprecipitation). We propose that keratinocyte-derived IL
      7 promotes not only the growth, but also the phenotypic maturation of DETC,
      thereby supporting the intraepidermal development of a DETC network during the
      neonatal period.

PMID- 8869029
TI  - Increased expression of type VI collagen genes in cutis laxa fibroblasts.
AB  - Type VI collagen gene expression in cutis laxa was studied by measuring messenger
      RNA (mRNA) and protein production levels in four fibroblast strains from patients
      with congenital cutis laxa and comparing them with those in fibroblasts obtained
      from age-matched healthy subjects. Levels of type VI collagen mRNA were increased
      in all cutis laxa fibroblast strains and the levels of alpha 1 (VI) and alpha 3
      (VI) chain mRNAs increased in parallel. Increases in type VI collagen mRNAs
      correlated well with production levels of the corresponding proteins, as
      determined by immunological assay. These results suggest that increased type VI
      collagen gene expression is one of the characteristics of cutis laxa dermal
      fibroblasts and that this abnormality may be related to the skin changes in cutis
      laxa.

PMID- 8869030
TI  - Superantigen-induced cytokine expression in organ-cultured human skin.
AB  - Bacterial superantigen such as staphylococcal enterotoxin B (SEB) induced strong
      ICAM-1 expression in organ-cultured human keratinocytes. Other superantigens
      (SEA, SEC1, SEC2) but not mite antigen (Dermatophagoides) also induced ICAM-1
      expression both at protein and mRNA level. In contrast to ICAM-1, vascular
      endothelial cell expression of VCAM-1 was only demonstrated at mRNA level
      following ICAM-1 expression in keratinocytes. Patterns of cytokine expression in
      keratinocytes were variable. TNF alpha was strongly expressed in keratinocytes
      both at protein and mRNA level, while IL1 beta and IL1 alpha were only
      demonstrated at mRNA level. These results clearly demonstrated that bacterial
      superantigen could induce cell adhesion molecule expression in keratinocytes
      through the induction of various cytokines and play an important role in the
      induction of refractory eczematous lesions in atopic dermatitis.

PMID- 8869031
TI  - Identification of autoantibody to melanocytes and characterization of vitiligo
      antigen in vitiligo patients.
AB  - Patients with vitiligo have circulating antibodies to melanocytes. To identify
      vitiligo antibodies and characterize the antigens by vitiligo antibodies, sera of
      18 patients with vitiligo, 18 with Behcet's disease, 22 with syphilis and 14
      normal control subjects were analyzed by indirect immunofluorescence, live cell
      ELISA, and immunoblotting. In indirect immunofluorescent microscopy and live cell
      ELISA, most vitiligo sera showed positive immunofluorescence and high optical
      density on the surface of melanocytes cultured from normal and vitiligo patients,
      indicating that autoantibodies in the vitiligo sera may react with vitiligo
      antigens on the surface of melanocytes. When the same experiments were performed
      with malignant melanoma cell lines and fibroblasts, no significant differences in
      the immunofluorescence and optical density were observed between normal and
      vitiligo sera. And the sera of patients with Behcet's disease or syphilis showed
      no significant difference in the reaction of live cell ELISA to fibroblasts, IGR
      3 and melanocytes. The antibody titers of vitiligo patients in live cell ELISA
      decreased following systemic steroid treatments. Immunoblot analysis demonstrated
      that 44% of vitiligo sera was directed to melanocyte antigen with a molecular
      weight of 65 kDa. Inhibition assay using rabbit anti-melanocyte antibody showed
      inhibition of reaction between vitiligo sera and melanocytes in ELISA and
      immunoblotting. These findings support the hypothesis that the sera of vitiligo
      patients have autoantibodies mostly directed to the 65-kDa antigen and this
      antigen may originate mostly from the melanocyte surface.

PMID- 8869032
TI  - 1,25-Dihydroxyvitamin D3 increased beta-adrenergic adenylate cyclase response of
      fetal rat keratinizing epidermal cells (FRSK cells).
AB  - Using fetal rat keratinizing epidermal cells (FRSK), the effects of 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) on adenylate cyclase system were investigated.
      The beta-adrenergic adenylate cyclase response was significantly increased by the
      stimulation of 1 x 10(-7) M 1,25(OH)2D3. The effect was observed by 6 h and
      continued for at least 48 h. The 1,25(OH)2D3-induced beta-adrenergic augmentation
      effect was dose-dependent and the maximal response was observed at a
      concentration of 1 x 10(-7) M 1,25(OH)2D3. Other adenylate cyclase systems
      (adenosine, prostaglandin E2 and histamine) were not affected by treatment with
      1,25(OH)2D3. The thymidine incorporation in FRSK cells was not significantly
      affected by 1,25(OH)2D3 treatment. Forskolin-induced cyclic AMP accumulation was
      significantly increased by 1,25(OH)2D3 treatment. Cholera toxin-induced cyclic
      AMP accumulation was moderately increased, but this was statistically not
      significant. Northern blot hybridization showed that none of the mRNAs (the beta
      2-adrenergic receptor, the alpha subunits of the stimulatory or inhibitory
      guanine nucleotide binding proteins, Gs alpha, Gi2 alpha, Gi3 alpha) were
      significantly altered by 1,25(OH)2D3 treatment. We have already reported that the
      beta-adrenergic response was increased by dexamethasone and inhibited by
      retinoids in FRSK cells. The addition of both 1,25(OH)2D3 and dexamethasone to
      the incubation medium resulted in an additive augmentation. On the other hand,
      the beta-adrenergic augmentation by the 1,25(OH)2D3 treatment was suppressed by
      the addition of all trans-retinoic acids. Our results indicate that 1,25(OH)2D3
      induces beta-adrenergic augmentation without an alternation of thymidine
      incorporation of FRSK cells.

PMID- 8869033
TI  - Disaccharide analysis of human skin glycosaminoglycans in sun-exposed and sun
      protected skin of aged people.
AB  - The total amount of main disaccharide units of skin glycosaminoglycans was
      compared between sun-exposed (n = 12) and sun-protected skin (n = 14) of aged
      people using high performance liquid chromatography after labeling with 1-phenyl
      3-methyl-5-pyrazolone. The total amount of main disaccharide units in sun-exposed
      skin was comparable to sun-protected skin presumably due to the diversity of
      individuals. Consequently, we compared sun-exposed skin with sun-protected skin
      in identical individuals (n = 6). The total amount of main disaccharide units in
      sun-exposed skin was significantly greater than that in sun-protected skin (P <
      0.05). In addition, the ratio of delta Di-HA (hyaluronic acid, HA)/delta Di-4S
      (dermatan sulfate, DS) in sun-exposed skin showed a decreasing trend as compared
      with sun-protected skin in four of six individuals. These results are in
      agreement with our previous results obtained in animal experiments of photoaging,
      i.e., hairless mouse skin exposed to repeated UV irradiation showed an increase
      in total amount of main disaccharide units and a decrease in the ratio of delta
      Di-HA(HA)/delta Di-4S(DS). We could confirm similar changes in skin
      glycosaminoglycans both in human and murine photoaging supporting the appropriate
      rationale for using the hairless mouse as an animal model for photoaging. Again,
      disaccharide analysis should provide a useful method to examine the biochemical
      changes of skin glycosaminoglycans in human photoaging.

PMID- 8869034
TI  - Effect of human basic fibroblast growth factor on fibroblast proliferation, cell
      volume, collagen lattice contraction: in comparison with acidic type.
AB  - Human recombinant basic fibroblast growth factor (bFGF) is a potent mitogen for
      normal human dermal fibroblasts in the presence of heparin which binds to and
      stabilizes it. The optimal mitotic response is obtained with a concentration of 1
      ng/ml of bFGF in monolayer cultures (non-differentiated fibroblasts) as well as
      in the better-differentiated fibroblasts obtained through the 'collagen lattices'
      culture system (fibroblasts embedded in a 3-dimensional collagen gel) achieving a
      doubling of the cell number in 8 days. Despite increasing the number of cells,
      bFGF decreases the ability of fibroblasts to contract collagen fibers. This
      inhibition is concentration-dependent and reaches a plateau at a dose of about 1
      ng/ml. This effect is associated with a bFGF-induced decrease of fibroblast
      volume. Various dosing regimens indicate that although the highest response was
      obtained by daily dosing nearly optimal response was obtained either by early
      daily dosing or short intermittent treatment. Interestingly, the fibroblast
      mitotic response to bFGF decreases steadily when fibroblasts mature in collagen
      gels. The mitogenic properties of bFGF associated to its ability to inhibit
      fibroblasts contraction, if demonstrated in vivo, may be of interest in the
      management of wound healing.

PMID- 8869035
TI  - Detection of IL-1 alpha, IL-1 beta and IL-1 receptor antagonist in blister fluid
      of bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. In
      addition to autoantibodies, complement activation and inflammatory cells are
      necessary for lesion formation. In this study, we investigated the potential
      involvement of IL-1, secreted by various inflammatory and non-inflammatory cells,
      in BP lesions. We determined IL-1 alpha IL-1 beta and IL-1 receptor antagonist in
      both blister fluid and concurrent serum samples of 10 BP patients by ELISAs. For
      comparison, we assayed experimentally generated suction blisters from 10 healthy
      volunteers. IL-1 beta levels were significantly elevated in BP blisters, whereas
      levels of IL-1 alpha were decreased relative to those in controls. In concurrent
      serum samples, no IL-1 alpha or IL-1 beta were detected in patients or controls.
      Levels of IL-1 receptor antagonist were significantly higher in BP blisters in
      relation to both concurrent sera and suction blisters. Our data indicate the
      release of IL-1 beta, IL-1 receptor antagonist, and to a lesser extent, of IL-1
      alpha, at the site of blister formation in BP and support the notion that cell
      mediated immune mechanisms may contribute to blister formation in this disease.

PMID- 8869036
TI  - A study of white dermographism in atopic dermatitis.
AB  - Vascular responses of 15 adults with atopic dermatitis (AD), 15 with psoriasis
      and 15 with normal skin were studied using an automated dermographometer we have
      designed. The type of colour change, time to onset and the duration of responses
      were recorded after a constant stroking force was applied to the skin of each
      subject. Of the 15 patients with atopic dermatitis, 11 had white dermographism
      (WD) with abnormal looking skin and four had red dermographism (RD) with normal
      looking skin. All the control subjects had RD. WD in AD had a significantly
      longer time to onset and shorter duration of response than RD in controls (P <
      0.01), whereas RD in AD had a significantly shorter duration of response than RD
      in controls (P < 0.01). WD in AD changed to RD after topical corticosteroid
      treatment and this post-treatment RD was quantitatively similar to the RD in AD.
      We have quantified, for the first time, a subnormal form of RD in clinically
      normal skin of patients with AD, which is different from that of the RD in normal
      subjects. We have also shown that WD in AD is altered to this subnormal form of
      RD after treatment with topical coricosteroids.

PMID- 8869037
TI  - Quantitative analysis of ferrochelatase mRNA in blood cells of erythropoietic
      protoporphyria patients.
AB  - Ferrochelatase (FC; heme synthetase, EC 4.99.1.1.) catalyses the synthesis of
      heme from protoporphyrin IX, the final step in the heme synthetic pathway. The
      hereditary deficiency of this enzyme gives rise to erythropoietic protoporphyria
      (EPP). We developed a rapid, non-radioactive means of measuring human FC mRNA
      levels in the EPP patients. It is based on the reverse transcriptase-polymerase
      chain reaction (RT-PCR) performed on the RNA obtained from peripheral blood. The
      amplified DNA was detected by agarose gel electrophoresis with ethidium bromide
      staining and the fluorescent intensity was measured by scanning densitometry
      applied directly to Polaroid 665 negative film. The relative expression level of
      FC mRNA, compared with that of glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
      mRNA, was estimated at several points in the exponential phase of PCR cycles or
      at a point in the exponential phase of PCR performed on serially diluted the cDNA
      samples. The estimate of the FC mRNA by this method correlated well with the
      level of the FC mRNA measured by Northern blotting in the EB virus-transformed
      lymphocytes of the same patients. The level of the FC mRNA appeared to vary among
      the patients in whom a decreased level of enzymatic activity was indicated.

PMID- 8869038
TI  - Ascorbic acid reduces tropoelastin levels in culture medium of chick skin
      fibroblasts.
AB  - Ascorbic acid reduced tropoelastin levels in the culture medium of embryonic
      chick skin fibroblasts to one-third or one-fourth of their original value in a
      dose- and exposure time-dependent manner under conditions in which collagen
      synthesis was stimulated 1.8-fold. The steady-state level of elastin mRNA
      remained essentially constant, whereas the collagen mRNA content increased in
      proportion to the increase in collagen synthesis with ascorbic acid treatment.
      These results suggest that the reduction of tropoelastin levels is not controlled
      by the elastin mRNA level but, rather, is related to the posttranslational
      modification of the tropoelastin molecule.

PMID- 8869039
TI  - [Inappropriate antidiuretic hormone secretion disclosing a second primary lung
      cancer 5 years after complete remission of a small cell lung carcinoma].
AB  - We report the case of a female patient who developed a second contralateral small
      cell lung carcinoma (SCLC) five years after a right upper lobe SCLC treated by
      sequential chemotherapy and chest radiation therapy. This second primary
      neoplasia was revealed by an isolated and symptomatic syndrome of inappropriate
      antidiuretic hormone secretion. Specific evolution of long-term survivors after
      SCLC are discussed, including consequences of combined radiochemotherapy and poor
      prognosis associated with persistence of tobacco smoking exposure.

PMID- 8869040
TI  - [MDR (Multiple Drug Resistant) type of resistance to chemotherapy in clinical
      practice].
AB  - Multifactorial resistance is the main mechanism of chemotherapy failure in
      cancers. Multidrug resistance (MDR) is related to the expression of a 170 kDa
      membrane glycoprotein, the so-called P-glycoprotein (P-gp). This protein is able
      to extrude drugs of various structures and mechanisms out of the cytoplasm. P-gp
      is a pronostic value in hemopathy as well as in child sarcoma, osteosarcoma and
      neuroblastoma. Modulator agents of different generations are capable of
      inhibiting P-gp. MDR modulation is obtained in hemopathies and is associated with
      an eradication of the P-gp (+) cell clones. In solid tumors, clinical trials
      using verapamil or cyclosporin are not so convincing. It is likely that other
      mechanisms of resistance are responsible for tumor progression, such as the MRP
      system, glutathion and topoisomerases. A better knowledge of multifactorial
      resistance and drug synthesis counteracting these resistance mechanisms will
      allow to elaborate new therapeutic basis for cancer therapy.

PMID- 8869041
TI  - [Modulation of cisplatin cytotoxicity by amphotericin B in six human cell lines
      of medullary thyroid cancer].
AB  - Medullary thyroid carcinoma (MTC) is frequently resistant to chemotherapy. In
      this work, we have studied the effect of cisdiamminedichloroplatinum (II) (CDDP)
      in six MTC human cell lines and we have tried to reverse the resistance to CDDP
      with amphotericin B (AmB). We also studied the metabolism of glutathione (GSH)
      and the presence of the glutathione-sulfotransferase pi (GST pi) mRNA in the MTC
      cell lines. The cisplatin-induced cytotoxicity was evaluated with the 3-4,5
      dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) test, the neutral red (NR)
      uptake and with total GSH measurement in six cell lines, TT cell line and five
      cell lines that we isolated. The cultures were performed with or without AmB (5
      micrograms/mL). Intracellular GSH was measured in TMC cells and compared to the
      levels obtained in six normal thyroid tissues. The expression of GST pi mRNA was
      evaluated by Northern blotting in the different cell lines. A CDDP-induced
      cytotoxicity was obtained in the six cell lines at doses inhibiting 50% of the
      cellular proliferation (IC50) varying from 6 to 40 micrograms according to the
      tests and the cells tested. A low concentration of AmB (5 micrograms/mL)
      potentiated the cisplatin toxicity after a 48-h coincubation of TMC in all cases.
      GSH levels in TMC cell lines were identical to those found in normal cells. GST
      pi mRNA was detected in all the TMC lines, except in TT cell line. In conclusion,
      CDDP was toxic for all the TMC cell lines and AmB potentiated this antitumoral
      effect. On the contrary, GSH and GST pi do not seem to be involved in the
      mechanisms of the resistance in these cell lines.

PMID- 8869042
TI  - [A study of the expression of MDR1 gene in solid tumors. Initial results of a
      multicenter evaluation].
AB  - The results obtained from 12 laboratories, dealing with six identical malignant
      solid tumors, assessing MDR1 phenotype using molecular techniques and
      immunohistochemistry have been compared. Moreover, comparisons between results of
      MDR1 gene expression, quantified by RT-PCR or Northern blot analysis from 10 RNA
      and 10 cDNA samples, were also compared between eight laboratories. Results
      concerning solid tumors show frequent discrepancies between the results obtained
      by immunohistochemistry and molecular biology techniques. Moreover, inter
      laboratory discrepancies concerning immunohistochemistry techniques are observed,
      suggesting that the interpretation of staining is critical. Results of RT-PCR and
      Northern blot using RNA and cDNA show that discrepancies are less frequent than
      those observed using immunohistochemistry. However, Northern blot is not
      sensitive enough to be used in routine. The problems encountered using RT-PCR are
      the following: positivity threshold level, reproducibility and risks of cross
      contamination.

PMID- 8869043
TI  - [Multicentric evaluation of MDR phenotype in leukemia: intermediate analysis of
      the French study].
AB  - Thirty-six French centres are involved in an evaluation of the techniques used
      for MDR phenotype measurement. Until now, 14 samples of various kinds of leukemia
      (mainly acute myelogenous leukemia) and three cell lines with different levels of
      resistance were sent by one centre and tested. MRK16 antibody was used for flow
      cytometry and immunocytochemistry, RNA was measured by RT-PCR, rhodamine or
      anthracyclin efflux were tested for functional assay. Wide discrepancies were
      observed in the results, mainly with flow cytometry, specially for the samples
      with a probable low level of MDR1 expression. The importance of histogram
      interpretation was documented by the comparative analysis of results obtained on
      cells already marked with MRK16, fixed and sent to all centers. The use of the
      ratio of the mean of fluorescence, instead of percentage, should help for
      standardization. The use of only one control RNA (used at different dilutions)
      for standardisation of RT-PCR could help in decreasing the discrepancies
      observed. The mean of fluorescence should also be used for expressing the
      rhodamine cell content.

PMID- 8869044
TI  - [Simultaneous screening of cancers of the breast, cervix, colon and rectum. The
      Isere experience].
AB  - The mass screening program for cancer in the Isere department offers women
      between 50 and 69 years a medical consultation and three tests: mammography for
      breast cancer screening, Pap smear for cervical cancer screening, and hemoccult
      for colorectal cancer. During the first round, 29,570 women took part in the
      program, 21% had a mammography, 20% Pap smears and 25% a hemoccult. In breast
      cancer screening, the rate for further examination was 11.9%, the breast cancer
      detection rate was 5.4 per 1,000 women screened and the detection rate of
      invasive tumor < or = 10 mm: 2.0 per 1,000. In cervical cancer screening, the
      rate of abnormal examinations was 1.2%. The cervical cancer detection rate was
      1.5 per 1,000. The rate of positive hemoccult was 2.7% and the rate of colorectal
      cancers and polyps 10 mm or larger was 2.7 per 1000. Results of screening are
      satisfying, but compliance rate is too low. Acceptance rate must be examined in
      following rounds.

PMID- 8869045
TI  - [Contamination of cytapheresis by tumor cells: apropos of 39 breast cancer
      cases].
AB  - The purpose of the present study was the detection of tumor cells in aphereses
      after mobilization of peripheral blood stem cells (PBSCs) with G-CSF from 39
      breast cancer patients. Circulating tumor cells were searched using sensitive
      immunocytochemical technique (APAAP) with three anticytokeratin monoclonal
      antibodies. Counting of mononuclear cells and CD34 progenitor cells was also
      performed. Circulating tumor cells were detected in 35% of the patients.
      Cytokeratin-positive cells were detected in 45% of the patients of the metastatic
      group compared with 20% of the non metastatic one. Aphereses contamination was
      not correlated with lymph node involvement. Numbers of mononuclear cells and CD34
      cells were not significantly different in positive and negative PBSCs
      collections. In our study, presence of tumor cells was associated with advanced
      clinical stage and could not be related to a higher CD34 cells mobilization by G
      CSF.

PMID- 8869046
TI  - [Prognostic value of CA 125 initial half-life measured during first-line
      chemotherapy in 62 patients with epithelial ovarian cancer stage III or IV].
AB  - The prognostic value of CA 125 initial half-life in serum (Tb) during the first
      cycles of first-line chemotherapy was studied in 62 patients with stage III or IV
      ovarian cancer. The half-life was strongly correlated; 1) with the rate of
      biological remission (P < 0.001). This one was respectively equal to 94.7% when
      Tb was lower than 20 days, 66.6% when Tb was between 20 and 40 days and 7.7% when
      Tb was higher than 40 days; 2) with the rate of histological remission (P <
      0.001) which was equal to 66.6% when Tb was lower than 13 days; 3) with the speed
      of recurrence growth measured by the doubling time (dT) of CA 125. The median of
      dT was equal to 182 days when Tb was lower than 13 days, 63 days when Tb was
      between 13 and 20 days (P < 0.02) and 38 days when Tb was higher than 20 days (P
      < 0.001); 4) with the duration of disease-free survival (DFS) (P < 0.001): the
      medians were equal to 23.9 months, 18.0 months, 12.0 months, and 5.5 months,
      respectively, when Tb was lower than 13 days, between 13 and 20 days; 20 and 40
      days, and higher than 40 days; and 5) with the duration of overall survival (OS).
      The probability of survival at five years was equal to 48% when Tb was lower than
      13 days. This probability falled to 13%, 12%, and 8%, when Tb was respectively
      between 13 and 20 days, 20 and 40 days and higher than 40 days. Multiple
      regression analysis showed that CA 125 half-life was the most important
      prognostic factor for DFS and OS. Analysis of correlation allowed to identify a
      relation between: 1) dT and Tb [dT = Tb/[-0.305 + (0.0388)(Tb)]; P < 10(-4)]; 2)
      the slope of CA 125 initial regression (P) and DFS [DFS = 201.9e (-16.64*P); P <
      10(-8)]; 3) P and OS [OS = 285.0e(-17.00*P); P < 10(-7)]. The initial CA 125 half
      life measured during the first cycles of first time chemotherapy seemed to be a
      critical predictor of response to therapy.

PMID- 8869047
TI  - [Validation of a new interactive software monitoring a controlled-flow infusion
      pump for cisplatin dosage regimen adjustment].
AB  - Adaptive dosing of cisplatin (CDDP) results in reduced haematological and renal
      toxicity but it has never been clearly shown that it affects the tumoral response
      rate. Before undertaking a clinical randomized study of CDDP monitoring versus
      standard dose, a comparative study was performed between a new software dedicated
      to the interactive adjustments--the AJI software--and the APIS software for
      clinical pharmacokinetics which incorporates a bayesian procedure and a
      population information computed according to a three compartment model. CDDP was
      administered by continuous infusion at variable rates with a controlled flow pump
      during four days in order to reach the target of 1.3 mg/L at the end of the first
      day, and to maintain this level during the whole treatment. This study was
      carried out on two groups of patients. Group 1 (12 patients; 27 courses) received
      CDDP with sequential flow rates in order to obtain a population information to be
      used with AJI. For patients in group 2 (14 patients; 26 courses), doses (flows)
      were adapted in a prospective study using the AJI software two to three times the
      first day, then daily. They could have been adapted (retrospective study) after
      platin pharmacokinetic parameters identification by APIS. The dosage
      recommendations proposed by APIS the first day, from 12 hours to 24 hours, to
      reach the target of 1.3 mg/L at 24 hours, and then daily up to D4 (AAPT at Di) to
      maintain this level were compared to those which were really administered during
      the interactive treatment (DA at Di). There were no statistically significant
      difference for D2, D4 and for the total dose (118.7 +/- 20.1 mg and 118.5 +/-
      45.1 mg). The difference was statistically significant for D1 and D3 (P < 0.05).
      The inter-individual variability was less important with AJI (CV = 16.9% for DA
      total) than with APIS (CV = 38.0% for ADAPT total). The platin pharmacokinetic
      parameters identified the first day by APIS were not statistically different from
      those identified from the whole treatment for clearance (5.92 and 5.63 l/d) and
      Vtotal 87.8 and 93.1 L); the difference was statistically significant for
      Vinitial (34.7 and 42.5 L; P < 0.05) and the terminal half-life (13.1 and 15.5
      days; P < 0.05).

PMID- 8869048
TI  - [Cardiopulmonary resuscitation in cancer patients: experience of an intensive
      care unit in a cancer center].
AB  - The goal of this study was to determine the effectiveness and potential
      indications of cardiopulmonary resuscitation (CPR) in medical cancer patients. A
      retrospective analysis of the records of patients admitted between November 1985
      and January 1992 in the medical ICU of a cancer hospital and having had cardiac
      arrest was performed. Cardiac arrest occurred in 49 cancer patients. CPR was
      successful in 19 (39%), but only 5 (10%) were discharged alive from the hospital.
      CPR was successful in all eight patients in which cardiac arrest was the
      consequence of an acute cardiovascular drug toxicity, even if cancer was
      metastatic and treatment intent not curative, while it was effective in only 25%
      of those in which cardiac arrest was an ultimate complication of various
      problems, like septic shock or respiratory failure complicating the neoplastic
      disease. In cancer as in other types of disease, CPR is mainly indicated when
      cardiac arrest is the consequence of and acute insult.

PMID- 8869049
TI  - Cost-effectiveness of carotid endarterectomy.
AB  - Carotid endarterectomy (CEA) reduces the risk of stroke in symptomatic patients
      with high-grade carotid stenosis. In this study, we evaluated the long-term,
      societal cost-benefit ratio of endarterectomy using a decision analysis model. We
      reviewed the results of 150 CEAs performed at an academic center and established
      a Markov model comparing cohorts of patients who experienced transient ischemic
      attacks and then underwent observation, aspirin therapy, or CEA. The cost
      effectiveness of CEA was estimated using perioperative complication rates from
      our review and from the North American Symptomatic Carotid Endarterectomy Trial.
      Stroke and mortality rates were estimated from the literature. Cost estimates
      were based on medicare reimbursement data. Among the 150 CEAs reviewed,
      complications included major stroke (0.67%), minor stroke (1.33%), myocardial
      infarction (1.33%), pulmonary edema (0.67%), and wound hematoma (3.33%). There
      were no deaths or intracerebral hemorrhages. Using complication rates from our
      review, CEA produced cost savings of $5730.62 over the cost of observation and
      $3264.66 over the cost of aspirin treatment. CEA extended the average quality
      adjusted life expectancy 15.8 months over that of observation and 13.2 months
      over that of aspirin. Substituting the North American Symptomatic Carotid
      Endarterectomy Trial results, CEA yielded savings of $2997.50 over the cost of
      observation and $531.54 over the cost of aspirin. Quality-adjusted life
      expectancy was extended 13.8 months compared with observation and 11.2 months
      compared with aspirin therapy. This analysis demonstrates that when performed
      with low perioperative morbidity and mortality rates, CEA is a highly cost
      effective therapy for symptomatic carotid stenosis and results in substantial
      societal cost and life savings.

PMID- 8869050
TI  - Clinicopathological heterogeneity in the classification of mild head injury.
AB  - Research examining the neurobehavioral outcome after mild head injury has yielded
      inconsistent and contradictory findings. Such findings have been attributed to a
      variety of methodological weaknesses, such as failure to consider the preinjury
      status of the patient, lack of control groups, and variability in outcome time
      points. However, few researchers have examined the adequacy of the current
      diagnostic criteria. A Glasgow Coma Scale (GCS) score of 13 to 15 is one of the
      primary criteria in the classification of mild head injury. We propose that the
      use of GCS Scores 13 to 15 permits excessive heterogeneity in injury severity and
      contributes to variability in neurobehavioral outcome. The purpose of this study
      is to examine the relationship of admission GCS scores to variables indicative of
      injury severity. The case records of 3370 patients consecutively admitted to a
      Level I trauma center with nonmissile head injuries, positive loss of
      consciousness, and admission GCS scores of 13 to 15 were reviewed. The frequency
      of positive computed tomographic scan findings and the need for neurosurgical
      intervention within the first 24 hours were recorded. A chi 2 analysis revealed
      statistically significant differences between the frequency of positive computed
      tomographic scans and the need for neurosurgical intervention in patients with
      GCS scores of 13 versus 14, 14 versus 15, and 13 versus 15. These results
      indicate significant differences in injury severity among patients with admission
      GCS scores of 13 to 15. The implicit assumption of clinicopathological
      homogeneity among patients with such scores is challenged by these data. This
      study demonstrates the need for more precise research diagnostic criteria in the
      study of neurobehavioral outcome after mild head injury. These findings also
      provide compelling evidence for the re-examination of the classification of mild
      head injury. Serious consideration must be given to the segregation of patients
      with GCS scores of 15 from those with scores of 14 and 13.

PMID- 8869051
TI  - Intramedullary subependymoma of the spinal cord.
AB  - A consecutive series of six patients underwent operative resection of
      intramedullary spinal cord subependymomas between January 1981 and August 1993.
      Three men and three women between the ages of 26 and 66 years experienced
      symptoms for a mean of 50 months preceding diagnosis. The locations of the tumors
      were predominantly cervical or cervicothoracic, except in one patient. At
      operation, a complete extirpation was achieved in each patient. No patient
      received further adjunct therapy. There has been no tumor recurrence in any
      patient after a mean follow-up period of 39 months. Most of the intramedullary
      spinal cord tumors are either ependymomas or astrocytomas. Clinical histories,
      physical examinations, and radiographic investigations are not conclusive for
      absolute diagnosis of subependymomas; however, intraoperative gross observations
      have shown these well-demarcated tumors to be located eccentrically within the
      spinal cord. Pathological examinations demonstrate tumors with sparse
      cellularity, clustering of cells, and dense fibrillary stroma. Proliferation
      studies with the mouse monoclonal antibody MIB-1 reconfirm the slow growth
      potential of these benign tumors.

PMID- 8869052
TI  - High-grade astrocytomas in children: radiologically complete resection is
      associated with an excellent long-term prognosis.
AB  - High-grade astrocytomas comprise approximately 10% of intracranial tumors in
      children. A better prognosis in children than in adults has been reported for
      patients with these neoplasms, although the reasons for this survival advantage
      are uncertain. To determine whether any consistent factors were associated with
      long-term survival, we reviewed the records of 31 children with high-grade non
      brain stem gliomas who were treated at our institution between 1975 and 1992.
      Histology was reviewed and classified according to the World Health Organization
      scheme, and neuroimaging studies were examined to determine the extent of
      resection, in both instances by individuals who were unaware of the patients'
      outcomes. The median overall survival for the 28 patients who survived the
      perioperative period was 18.5 months; 10 (36%) are currently alive, with a median
      follow-up of 70.5 months. The median progression-free survival (PFS) was 10.5
      months; eight patients (29%) remain progression-free with a median follow-up of
      78 months. The extent of resection at initial operation was associated most
      closely with PFS and overall survival as revealed by multivariate analysis. The
      14 patients who underwent subtotal (< 90%) resection and the 7 who underwent near
      total (90-99%) resection had median PFS of 5.5 and 11 months, respectively (P =
      0.38), and overall survival of 10.5 and 25 months, respectively (P = 0.02). None
      of the seven patients who underwent gross total removal of tumor as confirmed by
      postoperative imaging had disease progression, with a median follow-up of 84
      months (P < 0.0001). All of the tumors that underwent gross total resection were
      situated within the cerebral hemispheres; five of the seven patients had seizures
      as a presenting symptom. Both tumor location and seizures were significantly
      associated with outcome as determined by univariate analysis, but because of the
      overwhelming impact of resection extent on outcome, these factors were not
      independently associated with outcome as revealed by multivariate analysis.
      Histology was associated with outcome in the subgroup of patients with
      incompletely resected hemispheric tumors, in which children with anaplastic
      astrocytoma had a significantly better PFS than those with glioblastoma
      multiforme (P = 0.009). In summary, our results support the role of cytoreductive
      surgery in the treatment of cerebral hemispheric high-grade astrocytomas in
      children, which may encompass a biologically distinct group of tumors that, by
      virtue of their location and growth characteristics, are amenable to aggressive
      resection. The prognosis for children with deep-seated lesions and for those with
      subtotally resected hemispheric lesions is generally poor with conventional
      therapy.

PMID- 8869054
TI  - The effectiveness of papilledema as an indicator of raised intracranial pressure
      in children with craniosynostosis.
AB  - Craniosynostosis management partially depends on the detection and treatment of
      elevated intracranial pressure (ICP). Examination for papilledema is considered
      to be the most reliable screening method for identifying raised ICP, but its
      effectiveness has not been defined. One hundred and twenty-two children with
      craniosynostosis who underwent funduscopic examinations and then Camino ICP
      monitoring were studied. All eye examinations were performed by an
      ophthalmologist after pharmacological pupillary dilation. Fifteen patients (12%)
      had papilledema. Subsequent ICP monitoring showed that the median ICP was 12.7 mm
      Hg, with 41 patients (34%) having elevated ICPs (> 15 mm Hg). Those with
      papilledema had higher ICPs (17.5 +/- 3.2 versus 12.7 +/- 5.5 mm Hg), were older
      (5.9 +/- 4.7 versus 1.9 +/- 2.6 years), and were more likely to have craniofacial
      syndromes (73 versus 41%) than those without papilledema (P < 0.05). Patients
      with both elevated ICPs and papilledema were older (5.9 +/- 4.7 versus 1.6 +/-
      1.4 years) and more likely to have multiple-suture synostosis (92 versus 61%)
      than those with elevated ICPs and no papilledema (P < 0.05). The presence of
      papilledema was a specific (98%) indicator of raised ICP, but its sensitivity was
      age-dependent. It was 100% sensitive in children older than 8 years, but it
      indicated elevated ICP in only 22% of younger patients. These results suggest
      that ICP monitoring to document elevated ICP is unnecessary in children older
      than 8 years who have detailed ophthalmological examinations. In the younger
      child, the presence of papilledema reliably indicates elevated ICP but its
      absence does not rule out elevated ICP; formal ICP measurement has a greater role
      in detecting elevated ICP in these patients.

PMID- 8869053
TI  - Effects of medulloblastoma resections on outcome in children: a report from the
      Children's Cancer Group.
AB  - We reviewed the data of children with high-stage primitive neuroectodermal tumors
      (medulloblastomas) who were treated on Children's Cancer Group-921 protocol to
      evaluate the correlation between tumor resection and prognosis. Patients enrolled
      in the study had either tumors that were operatively categorized to be Chang
      tumor stage 3b or 4, postoperative residual tumors > 1.5 cm2, or evidence of
      tumor dissemination (Chang metastasis Stages [M Stages] 1-4) at diagnosis.
      Resections were analyzed in two ways, as follows: 1) by the extent of resection
      (percent of the tumor that was removed), as estimated by the treating
      neurosurgeon; and 2) by the extent of residual tumor (how much of the tumor was
      left), as estimated from postoperative scans. Two hundred and three children were
      enrolled in the study with institutional diagnoses of primitive neuroectodermal
      tumors-medulloblastomas; diagnoses were confirmed by central neuropathological
      review in 188 patients. Progression-free survival (PFS) at 5 years was 54%
      (standard error, 5%). As in previous Children's Cancer Group studies, age and M
      stage correlated with survival; PFS was significantly lower in children 1.5 to
      3.0 years old at diagnosis and in those with any evidence of tumor dissemination
      (M Stage 1-4). On univariate analysis, neither extent of resection nor extent of
      residual tumor correlated with PFS. However, adjusting for other factors, extent
      of residual tumor was important; PFS was 20% (standard error, 14%) better at 5
      years in children with no dissemination (M Stage 0) who had < 1.5 cm2 of residual
      tumor (P = 0.065) and was 24% (standard error, 14%) better at 5 years in children
      > 3 years old with no tumor dissemination (M Stage 0) and with < 1.5 cm2 residual
      tumor (P = 0.033). On the basis of our observations, we conclude that extent of
      tumor resection, as estimated by the neurosurgeon, does not correlate with
      outcome but that extent of residual tumor does correlate with prognosis in
      certain children (those who are > 3 years old, with no tumor dissemination). In
      contrast to age and M stage, the major factors associated with outcome, residual
      tumor is an important variable in outcome, one that neurosurgeons can control.

PMID- 8869055
TI  - Thoracic vertebrectomy and reconstruction using a microsurgical thoracoscopic
      approach.
AB  - A video-assisted thoracoscopic microsurgical approach was developed in the
      laboratory and subsequently used clinically to resect abnormalities of the
      thoracic vertebrae, to decompress the thoracic spinal cord, and to reconstruct
      the thoracic vertebral bodies. This report describes the development of the
      clinical operative techniques for microsurgical thoracoscopic vertebrectomy,
      neural decompression, and spinal reconstruction. This minimally incisional
      approach was clinically used in 17 patients to treat vertebral osteomyelitis,
      tumors, and compression fractures. Microsurgical thoracoscopic techniques were
      performed using several narrow, flexible, working portals placed in small
      incisions in the intercostal spaces. Access to the thoracic spine was achieved
      through the pleural cavity after temporary deflation of one lung using a double
      lumen endotracheal tube. The parietal pleura, segmental vessels, and rib heads
      were dissected off the surfaces of the involved vertebrae to expose the region of
      interest. Long narrow spine dissection tools were used to perform the spinal
      decommpression and reconstruction. This technique achieved the same amount of
      spinal dissection as that achieved with conventional open spinal procedures and
      used microsurgical visualization techniques. The small incisions with reduced
      soft tissue dissection may reduce postoperative pain, shorten the length of
      hospitalization, and have cosmetic and functional advantages. Thoracoscopic
      vertebrectomies and reconstruction of the spine were technically feasilble
      procedures that were performed with excellent clinical results. This minimally
      incisional technique provides a viable alternative to thoracotomy or to
      posterolateral approaches for thoracic vertebrectomy and vertebral body
      reconstruction.

PMID- 8869056
TI  - Surgical management of dumbbell tumors of the cervical spine.
AB  - Twelve patients with benign dumbbell tumors of the cervical spine were treated
      surgically between March 1991 and July 1994. Gross total resection was achieved
      in 11 patients, using a single-stage modified posterior midline exposure with
      laminectomy and complete unilateral facetectomy. This exposure provides
      contiguous intraspinal, foraminal, and extraforaminal access that extends up to 4
      cm from the lateral dural margin. The surgical considerations of these tumors,
      including the surgical technique, potential spinal instability, vertebral artery,
      and risk of nerve root injury, are presented.

PMID- 8869057
TI  - Stereotactic microsurgical craniotomy for the treatment of third ventricular
      colloid cysts.
AB  - The treatment of colloid cysts remains controversial. This article reports on 18
      patients with colloid cysts of the third ventricle who presented to the
      University of Michigan between January 1990 and June 1995. Two patients had
      conventional transcortical-transventricular approaches; the remaining 16 patients
      underwent a stereotactic modification of the transcortical approach, using a
      specially designed cylindrical retractor, for the resection of their colloid
      cysts. Minor morbidity and no mortality have been associated with this technique.
      There have been no instances of recurrence during the period of this report. The
      mean operative time for the two conventional craniotomies was 233 minutes,
      compared with 129 minutes for the stereotactic craniotomies. Our technique allows
      for a limited craniotomy and limited cortical disruption. It is not dependent on
      ventricular size. Localization of the colloid cyst is trivial because of modern
      stereotactic technology, and all standard microsurgical techniques can be used.
      The retractor is readily adaptable to any Leksell system. This technique shortens
      operative time, compared with conventional craniotomy, and allows for definitive
      treatment of the lesion.

PMID- 8869058
TI  - Enhanced optical imaging of human gliomas and tumor margins.
AB  - One of the potential variables affecting the overall survival and quality of life
      of patients with intracranial gliomas is the extent of tumor resection that
      results in the smallest volume of residual disease. A technique involving
      enhanced optical imaging of human gliomas has the potential to localize tumors,
      identify tumor remaining at the resection margins, and determine the grade of the
      tumor. In a preliminary study involving nine patients undergoing surgery for the
      removal of intrinsic brain tumors, enhanced optical imaging was performed using
      indocyanine green as an intravenous contrast-enhancement agent. Optical images
      were obtained before and after injection of the indocyanine green. The studies in
      the nine patients showed differences in the dynamic optical signals among normal
      brain, low-grade astrocytomas, and malignant astrocytomas. Optical imaging of the
      resection margins in malignant tumors showed differences between adjacent normal
      tissue and remaining tumor tissue. Enhanced optical imaging of human gliomas
      using a contrast-enhancing dye, indocyanine green, provides a potential means to
      differentiate between normal brain and tumor tissue at the cortical surface and
      the depths of the resection margins. Having the ability to obtain real-time
      information and feedback in the operating room may allow neurosurgeons to
      maximize the extent of tumor resection while sparing normal brain and increasing
      the diagnostic accuracy of intraoperative biopsies. Enhanced optical imaging
      potentially could facilitate the accuracy and safety of surgery when tumors are
      removed at sites even outside the central nervous system.

PMID- 8869059
TI  - Repeat stereotactic radiosurgery of arteriovenous malformations: factors
      associated with incomplete obliteration.
AB  - Second stereotactic radiosurgery procedures were required in 45 patients with
      arteriovenous malformations (AVMs) who initially had incomplete obliteration.
      Repeat radiosurgery was performed at a median of 39 months (range, 24-71 mo)
      after the first stage. The median AVM volume at the first procedure was 6.0 ml
      (range, 0.2-18.0 ml). Thirty-seven patients (82%) had AVMs of Spetzler-Martin
      Grades III through VI. A retrospective analysis revealed definite causes for
      incomplete obliteration after the first procedure in 33 patients (73%).
      Incomplete angiographic definition of the nidus was the most frequent factor
      (57%) associated with failed radiosurgery. Three patients (7%) had recanalization
      of the AVM nidus after prior embolization; four patients (9%) had incomplete
      nidus recognition, because AVM vessels were not visualized in the presence of a
      hematoma. "Radiobiological resistance" was another potential factor associated
      with failed radiosurgery in 17 patients (38%). Our current technique for volume
      determination and dose planning includes stereotactic magnetic resonance
      angiography, magnetic resonance imaging, and complete cerebral angiography
      (including superselective and external carotid artery injections, as indicated).
      Integrated multiplanar high-resolution imaging will likely increase the rate of
      AVM obliteration after stereotactic radiosurgery.

PMID- 8869060
TI  - Anosmia after anterior communicating artery aneurysm surgery: comparison between
      the anterior interhemispheric and basal interhemispheric approaches.
AB  - The olfactory function could be examined in 101 of 138 patients with anterior
      communicating artery aneurysms, whom we treated during a recent 6-year period.
      Among them, 49 patients underwent surgery by the anterior interhemispheric
      approach and 52 underwent surgery by the basal interhemispheric approach. Fifteen
      patients (31%) exhibited anosmia after surgery by the anterior interhemispheric
      approach, whereas only one patient (1.9%) exhibited anosmia after surgery by the
      basal interhemispheric approach. Unilateral dural incision and unilateral brain
      retraction without elevation of the frontal lobe from the frontal base are
      important, because frontal lobe depression and elevation during surgery may
      injure the olfactory nerve.

PMID- 8869061
TI  - Functional magnetic resonance imaging of regional brain activity in patients with
      intracerebral gliomas: findings and implications for clinical management.
AB  - Functional magnetic resonance imaging (fMRI) was performed in seven patients
      harboring intracerebral gliomas proven by histological analysis using a
      noninvasive blood oxygen level-dependent technique based on the documented
      discrepancy between regional increases in blood flow and oxygen use in response
      to regional brain activation. We combined fMRI with conventional magnetic
      resonance imaging (MRI) during motor or language task activation experiments to
      investigate the potential usefulness of mapping regional brain activity as part
      of treatment planning in patients with intracerebral gliomas, in whom
      preservation of areas of functioning brain tissue is critical. Statistical fMRI
      maps were generated and directly mapped onto conventional MRI scans obtained at
      the same session. Of the five patients cooperative enough to remain motionless
      for the study and perform the task, the location of activation in the primary
      sensorimotor cortex on the side of the tumor was clearly displaced compared with
      that in the normal contralateral hemisphere in four patients. Four of the five
      tumors in these patients showed fMRI activation within the periphery of (or
      immediately adjacent to) areas of presumed tumor based on spin-echo MRI. In some
      patients with neurological deficit, the extent of activation was reduced on the
      side of the tumor as compared with the normal hemisphere. The supplemental motor
      area and the ipsilateral primary motor cortex were also reproducibly activated
      during motor tasks. We conclude that blood oxygen level-dependent fMRI can
      localize areas of cortical function in patients undergoing treatment planning for
      gliomas so that therapy can be directed away from regions of residual function.
      Our preliminary data suggest that functioning cortex within or adjacent to tumor
      margins can be demonstrated, which may correspond to partial preservation of
      clinical function. Our preliminary data also suggest that there may be a
      quantifiable difference on fMRI between activation in tumor-bearing cortex and
      activation in corresponding normal cortex in the contralateral hemisphere. We
      postulate that the magnitude of this difference may relate to the severity of
      patient deficit.

PMID- 8869062
TI  - Endovascular treatment of experimental aneurysms with liquid polymers: the
      protective potential of stents.
AB  - Liquid polymers have previously been used to treat experimental and human
      aneurysms. However, the delivery of a liquid embolic material into the cerebral
      circulation involves a high risk of irreversible vessel occlusion and stroke. To
      evaluate methods for the safe and effective treatment of experimental aneurysms
      with liquid polymer injection, we tested four different techniques to deliver
      cellulose acetate polymer (CAP) or N-hexyl-cyanoacrylate into canine side-wall
      carotid artery aneurysms. The animals were observed for 1 to 10 weeks after
      treatment. Two aneurysms were treated without protection of the distal
      circulation, one with CAP and another with N-hexyl-cyanoacrylate. In four cases,
      an angioplasty balloon was inflated within the parent artery during endosaccular
      injection of CAP. In two of these cases, the balloon was placed adjacent to the
      aneurysm orifice, resulting in simultaneous occlusion of both the aneurysm and
      the parent artery, and in the other two cases, the balloon was positioned
      proximal to the aneurysm, resulting in temporary flow arrest. Three aneurysms
      were treated with either CAP or N-hexyl-cyanoacrylate after implantation of a
      balloon-expandable tantalum stent within the parent artery across the aneurysm
      orifice. Complete angiographic obliteration was achieved in all but one case. One
      aneurysm ruptured. Another partially occluded aneurysm reopened 10 weeks after
      treatment. In all cases treated without stents, distal migration of the polymer
      resulted in either stenosis or occlusion of the parent arteries. The combination
      of stent implantation and polymer injection resulted in permanent aneurysm
      occlusion without detectable polymer migration. An intravascular stent deployed
      within the parent artery across the aneurysm orifice acted as a safety net during
      endosaccular polymer injection by allowing blood to flow from the aneurysm cavity
      while preventing distal migration of liquid polymer.

PMID- 8869063
TI  - Cellular uptake and transport of methylprednisolone at the blood-brain barrier.
AB  - Methylprednisolone (MP) is one of the most widely used neuroprotective drugs in
      neurosurgery. Our knowledge of its pharmacokinetics in the brain and, in
      particular, whether it can penetrate the blood-brain barrier (BBB) and act in the
      brain parenchyma is still limited. In this study, we used a vascular brain
      perfusion technique in guinea pigs, combined with a capillary depletion method,
      to determine brain uptake and transport of MP at the BBB. 3H-Labeled MP was
      delivered to the brain by carotid arterial infusions lasting from 1 to 10
      minutes; the effects of plasma protein binding, different concentrations of MP,
      and the glucocorticoid receptor inhibitor, RU486, were examined. The existence of
      a transport system was inferred from the observation that the volume of
      distribution of MP in the brain after perfusion exceeded by 2.6 to 6.3 times the
      plasma volume of the cerebrovascular space marker, sucrose. The rates of
      undirectional [3H]MP blood-to-brain transport of 0.5 to 0.7 microliters per
      minute per gram indicated significant but slow transfer. MP available for BBB
      transport was not restricted to its free plasma fraction but, instead, included
      the albumin- and globulin-bound fractions. A portion of steroid remained
      concentrated (sequestered) by the capillary endothelium, and from there, the
      label was distributed into brain parenchyma. Both MP binding and transport at the
      BBB exhibited saturable kinetics. RU486 produced an inhibition of MP BBB
      transport and binding with an affinity that seemed to be 30 to 60% higher than
      that of the steroid itself. We concluded that MP first binds to the brain
      capillaries and then crosses the BBB at a low rate, most likely by using a
      saturable mechanism that may involve a cytoplasmic endothelial glucocorticoid
      receptor.

PMID- 8869064
TI  - Comparison of cerebral blood flow measured by laser-Doppler flowmetry and
      hydrogen clearance in cats after cerebral insult and hypervolemic hemodilution.
AB  - Laser-Doppler flowmetry provides a continuous measurement of blood flow without
      violating the natural state of circulation. The linearity of the laser-Doppler
      and hydrogen clearance methods of blood flow measurement were compared using a
      protocol that produced changes in cerebral blood flow that might be experienced
      in a neurosurgical setting. Cerebral blood flow was measured in both hemispheres
      of 12 adult cats during the snaring of one common carotid artery, the
      intracisternal injection of 5 mg of 5-hydroxytryptamine creatinine sulfate, and
      hypervolemic hemodilution, which produced a 25% reduction in blood hematocrit.
      The percentage of baseline laser-Doppler flowmetry and hydrogen clearance flows
      showed an acceptable degree of correlation (R2 = 0.762) over the range of
      cerebral blood flows measured. More rigorous analysis using Bland and Altman's
      difference against mean test showed that 10 minutes after hemodilution, the two
      methods displayed a level of variation outside the limits of agreement (-21.85 to
      22.03%). Laser-Doppler flowmetry provided a noninvasive and continuous measure of
      blood flow, increasing the ability to observe instantaneous changes in cerebral
      microcirculation. However, laser-Doppler flowmetry did not record absolute blood
      flow, was affected by cerebral tissue shrinkage, and did not accurately measure
      flow under conditions of changed blood hematocrit.

PMID- 8869065
TI  - Expression and alternative splicing of Pit-1 messenger ribonucleic acid in
      pituitary adenomas.
AB  - Twenty-eight human pituitary adenomas were analyzed for the expression of Pit-1
      messenger ribonucleic acid (mRNA) by using reverse transcriptase-polymerase chain
      reaction analysis of frozen-section mRNA. Pit-1 mRNA was detected in all
      functioning tumors and in 9 of 11 nonfunctioning tumors. Pit-1 beta, which is a
      more active isoform of transcriptional factor for growth hormone than Pit- alpha
      and which arises from an alternative splicing mechanism, was detected in 14 of 17
      functioning tumors and in 5 of 11 nonfunctioning tumors. The transcript that
      corresponds to Pit-1T, which increases thyroid-stimulating hormone beta promoter
      activity in rat thyrotropic tumor cells, was not found. There was no significant
      difference in the total Pit-1 (alpha+beta) mRNA expression level between
      functioning tumors and nonfunctioning tumors. Growth hormone-producing tumors and
      other pituitary adenomas also showed no significant difference in the Pit-1
      beta/Pit-1 alpha expression ratio. Our data suggest that the major role of Pit-1
      gene in pituitary adenoma might not be involved in the regulation of hormone
      production.

PMID- 8869066
TI  - Dopamine D1, dopamine D2, and prolactin receptor messenger ribonucleic acid
      expression by the polymerase chain reaction in human meningiomas.
AB  - Previous studies have suggested the presence of high-affinity dopamine D1
      receptors and prolactin receptors in human cerebral meningiomas. In this study,
      using the polymerase chain reaction, we report the presence of the messenger
      ribonucleic acid (mRNA) for the dopamine D1 and D2 receptors and the prolactin
      receptor in meningioma tissue specimens and cell cultures derived from meningioma
      tissue. Dopamine D1 receptor mRNA was present in a majority of female tissue
      specimens and in all male tissue specimens. D2 receptor mRNA was detected in all
      specimens examined. Prolactin receptor mRNA was present in a little more than
      half of the female and male meningioma tumor specimens. The polymerase chain
      reaction products were directly sequenced to confirm the identity of these
      receptors in meningiomas and cell cultures. Ligand binding studies confirmed the
      presence of the dopamine D1 receptor in meningioma tissue specimens. In contrast,
      receptor studies with the dopamine D2 ligand [125I]4-iodospiperone failed to
      detect D2 binding in meningioma membrane preparations. These results suggest the
      existence of active dopamine D1 receptors in cerebral meningiomas.

PMID- 8869067
TI  - Antisense oligonucleotides for central nervous system tumors.
AB  - The poor prognosis associated with malignant primary brain tumors has led
      investigators to seek and develop new, innovative treatment modalities. Current
      adjuvant therapies lack tumor specificity, which can lead to toxic central
      nervous system side effects. Advances in molecular biology now allow specific
      gene sequences to be inserted or targeted in the malignant cell genome. Antisense
      oligodeoxynucleotides represent complementary nucleic acid sequences that can
      recognize and bind to target genes, resulting in the arrest of deoxyribonucleic
      acid transcription or the translation of messenger ribonucleic acid. Although the
      use of antisense oligodeoxynucleotides is still in the experimental stages, these
      molecules enter cells in tissue culture by simple diffusion or active endocytosis
      and temporarily inhibit cell proliferation in a time- and dose-dependent fashion.
      The ability of antisense oligodeoxynucleotides to recognize specific gene
      sequences and to down-regulate gene expression make them ideal agents for use in
      targeting oncogenes, such as c-myb, that are expressed in central nervous system
      neoplasms.

PMID- 8869068
TI  - Treatment of chronic unstable angina pectoris: use of a totally implantable
      programmable device for continuous intrathecal infusion of opiates: case report.
AB  - We report the case of a 70-year-old man with a 17-year history of angina
      pectoris, who had previously suffered two documented myocardial infarctions and
      undergone multiple diagnostic cardiac catheterizations, two coronary artery
      bypass operations, and several percutaneous transluminal coronary angioplasty
      procedures. The patient had experienced unstable angina for the past 3 years
      refractory to maximal medical therapy and was unsuitable for further attempts at
      revascularization. After a successful trial of epidural infusion of morphine, a
      totally implantable programmable continuous-infusion device with an intrathecal
      catheter was implanted in the patient on August 18, 1993, resulting in maintained
      pain resolution. His gardening, carpentry, and other activities of daily living
      were limited only by shortness of breath. Six months later, the pump treatment
      did not mask the development of a myocardial infarction. To the best of our
      knowledge, this is the first report of the use of continuous intrathecal infusion
      of morphine or the use of a totally implantable programmable infusion device for
      angina pectoris. We propose that in carefully selected patients with chronic
      unstable angina, continuous intrathecal infusion of morphine may relieve effort
      induced pain without resulting in myocardial infarction.

PMID- 8869069
TI  - Acute subdural hematoma caused by a ruptured giant intracavernous aneurysm: case
      report.
AB  - A case of a giant intracavernous carotid artery aneurysm that presented as an
      acute subdural hematoma is reported. The patient was initially treated
      unsuccessfully with endovascular aneurysmal embolization and subsequently
      underwent attempted microsurgical clipping with preservation of the parent
      artery. At operation, an angiogram showed occlusion of the parent vessel, and the
      aneurysm was trapped by occlusion of the internal carotid artery. The patient did
      well for 2 days postoperatively but then developed contralateral progressive
      hemiplegia and aphasia. Emergent subsequent exploration and middle cerebral
      artery embolectomy were performed, and the hemiplegia and aphasia resolved
      rapidly. At 2-year follow-up, the patient continues to do well. To our knowledge,
      this is the first reported case of a patient who survived an acute subdural
      hematoma caused by an intracavernous carotid artery aneurysm.

PMID- 8869070
TI  - Familial colloid cyst of the third ventricle: case report and review of
      associated conditions.
AB  - The cases of a father and his son who were diagnosed with pathologically
      confirmed colloid cysts of the third ventricle are presented. The familial
      occurrence of this tumor is rare and suggests that genetic factors may play a
      role in its formation. Consistent with the concept that the cyst originates as a
      developmental abnormality, it is associated with a variety of congenital defects.
      The conditions that are associated with these tumors are discussed.

PMID- 8869071
TI  - Intrasellar paraganglioma: report of a case in a sibship of von Hippel-Lindau
      disease.
AB  - Although uncommon, paragangliomas are known to affect the central nervous system.
      Those that arise in the sellar region are particularly rare. We report the
      clinicopathological features of a paraganglioma occurring in the setting of von
      Hippel-Lindau disease, a disorder in which paragangliomas are known to occur. We
      also present a review of the literature.

PMID- 8869072
TI  - Intracranial epithelioid hemangioendothelioma: case report.
AB  - We report the case of a 27-year-old man who underwent surgical excision of an
      intracranial extra-axial right temporal lesion. A preoperative embolization with
      the use of a mixture of N-butyl-cyanoacrylate, ultrafluid-lipiodol, and
      micronized tungsten was necessary to devascularize the tumor. The histological
      diagnosis was epithelioid hemangioendothelioma. The patient was neurologically
      intact and tumor-free 18 months after surgery. To our knowledge, this is the
      fifth patient reported with intracranial epithelioid hemangioendothelioma and the
      first adult patient for whom complete data are available.

PMID- 8869073
TI  - Epithelioid hemangioendothelioma of the lumbar vertebral column: case report and
      review of literature.
AB  - Epithelioid hemangioendothelioma is a recently described, rare vasoformative
      vascular tumor of variable biological behavior. Its principal sites of occurrence
      are soft tissues, liver, lung, and bone. There have been no formal case reports
      of this tumor occurring in the vertebral column, and there are no reports in the
      literature of surgical treatment for vertebral epithelioid hemangioendothelioma.
      We present a case of primary vertebral epithelioid hemangioendothelioma occurring
      in the L2 vertebral body. Surgical treatment, pathological findings, imaging
      characteristics, and a review of the literature are presented.

PMID- 8869074
TI  - Spinal cord compression from metastatic Leydig's cell tumor of the testis: case
      report.
AB  - A case of spinal cord compression from metastatic Leydig's cell tumor of the
      testis is presented. This 67-year-old man exhibited paraparesis and neurogenic
      bladder dysfunction secondary to a spinal epidural mass at the T5 level as the
      initial manifestation of his cancer. Surgical resection was undertaken for tissue
      diagnosis and spinal cord decompression. The histopathological features of the
      epidural mass and the excised left testicle were identical, indicative of
      Leydig's cell carcinoma. The literature is reviewed for previous experience with
      this exceedingly rare tumor. Unlike most metastatic spinal malignancies,
      radiation therapy is an ineffectual treatment modality for this tumor. Surgical
      resection is the only therapeutic option available for amelioration of spinal
      cord compression.

PMID- 8869075
TI  - Use of the extreme lateral approach in the surgical treatment of an intradural
      ventral cervical spinal cord vascular malformation: technical case report.
AB  - Vascular malformations on the ventral aspect of the spinal cord are difficult to
      access surgically. Recently, selected lesions have been treated with endovascular
      embolization. However, embolization using currently approved agents may not be
      permanently effective, and recanalization rates range from 25 to 83% in the
      literature. Additionally, many of these lesions are not amenable to endovascular
      treatment because of the inadequate diameter, tortuosity, or lack of collateral
      flow of the anterior spinal artery from which the feeding arteries arise.
      Surgical approaches to these lesions have been posterolateral or anterior. The
      posterolateral approach requires division of the dentate ligaments and
      occasionally the adjacent nerve root and then rotation of the cord itself to
      allow visualization of the lesion. The anterior approach involves a multilevel
      corpectomy requiring subsequent bone grafting and stabilization. Certain lesions
      are not readily approachable by either method. We describe the use of the extreme
      lateral approach to successfully access and obliterate a Type IVa perimedullary
      fistula located adjacent to the midline ventrally at the C1-C2 level in a 72-year
      old woman who had suffered a subarachnoid hemorrhage. The extreme lateral
      approach was originally designed to access neoplasms located ventral to the cord
      and brain stem; as a result of the posterior displacement of the spinal cord by
      the neoplasm, intraoperative visualization is improved. No posterior displacement
      was present with this malformation. Even without such cord displacement, the
      extreme lateral approach allowed excellent visualization of and access to the
      arteriovenous fistula, preserved important anatomic structures, and required
      essentially no rotation or compression of the spinal cord to successfully
      obliterate the lesion.

PMID- 8869076
TI  - Library: historical perspective.

PMID- 8869077
TI  - Electrophrenic respiration after intercostal to phrenic nerve anastomosis on a
      patient with anterior spinal artery syndrome: technical case report.

PMID- 8869078
TI  - Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60
      patients.

PMID- 8869079
TI  - P2U-purinergic receptor activation mediates inhibition of cAMP accumulation in
      cultured renal mesangial cells.
AB  - Extracellular ATP has been reported to exert mitogenic and contractile effects on
      cultured renal mesangial cells (MCs). Since it is possible that these actions
      involve changes in the cAMP second messenger system, we examined the effect of
      extracellular nucleotides on the accumulation of cAMP in rat MCs. ATP, UTP and
      adenosine 5'-0-(3-thio)triphosphate (ATP gamma S) (100 microM) had no significant
      effects on baseline cAMP levels, but inhibited forskolin-stimulated accumulation
      of cAMP by 21-75% in the presence of the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX). Maximal inhibitory effects were observed at 100 microM of
      ATP gamma S with a threshold dose of 1 microM. ATP gamma S, ATP and UTP were the
      most potent inhibitors indicating stimulation of the P2u receptor. The P2x
      agonists adenosine 5'-(alpha, beta-methylene) triphosphate and adenosine 5'
      (beta, gamma-methylene) triphosphate, and the P2y agonist 2-methylthio-ATP did
      not affect cAMP accumulation. Treatment with the P2 receptor antagonist suramin
      (200 microM) reduced the inhibition by 58%. The inhibitory effects of the
      nucleotides were significantly attenuated by preincubation with pertussis toxin
      (10-100 ng/ml). Inhibition of phospholipase C and protein kinase C did not
      prevent the inhibitory effect of the nucleotides. Inhibitors of forskolin
      stimulated cAMP accumulation had different effects on DNA synthesis in cultured
      MCs as measured by 3H-thymidine uptake at 48 h: ATP, ATP gamma S and the
      inhibitor of adenylyl cyclase, SQ 22536, stimulated DNA synthesis in MCs, while
      UTP showed no significant mitogenic effect. Agents which increased baseline
      levels of intracellular cAMP (forskolin, IBMX, dibutyryl-cAMP) significantly
      diminished DNA synthesis in MCs. The results indicate that the P2u-purinergic
      receptor mediates inhibition of forskolin-induced cAMP accumulation which is
      likely due to inhibition of adenylyl cyclase. This effect appears to be partially
      mediated by PTX-sensitive G proteins. While the increase in cAMP accumulation is
      anti-mitogenic, inhibition of cAMP accumulation by P2u receptors is not
      correlated with MC growth control. Thus, additional mechanisms other than
      inhibition of cAMP accumulation by P2u receptors are likely to be involved in the
      mitogenesis of extracellular ATP.

PMID- 8869080
TI  - Interaction between adrenergic agonists and forskolin on adenylate cyclase
      activity in the rabbit proximal tubule.
AB  - Using a micro-radioimmunoassay, cAMP was measured in single, isolated S2 proximal
      straight tubules dissected from rabbit kidneys to investigate the effects of
      adrenergic agonists on adenylate cyclase activity. The baseline activity of
      adenylate cyclase was low and unaffected by either the alpha 2 agonist clonidine,
      the beta agonist isoprenaline (in the absence or presence of 1 microM forskolin)
      or 1 microM forskolin. Adenylate cyclase activity was markedly stimulated by 20
      microM forskolin, an effect which was inhibited by 1 microM clonidine. The
      inhibition by clonidine was not apparent in the presence of the alpha 2
      antagonist yohimbine. These results confirm the inability of isoprenaline to
      stimulate adenylate cyclase in the rabbit proximal tubule and demonstrate the
      coupling of alpha 2 receptors, in an inhibitory fashion, to adenylate cyclase.
      The inhibitory action of the alpha 2-receptor agonist was independent of other
      hormone activity in the renal proximal tubule.

PMID- 8869081
TI  - The angiotensin I-converting enzyme inhibitor, cilazapril inhibits the platelet
      derived growth factor B chain expression in glomeruli of spontaneously
      hypertensive rats.
AB  - To clarify whether in vivo expression of growth factors in the glomerulus is
      induced in a hypertensive animal model, we investigated the expression of
      platelet-derived growth factor (PDGF) B chain, transforming growth factor beta
      (TGF-beta), and angiotensin II (Ang II) type 1 receptors in glomeruli of
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. We also
      investigated the effects of treatment with cilazapril, and angiotensin I
      converting enzyme inhibitor, on this expression. First, the expression of PDGF B
      chain, TGF-beta, and Ang II receptors from the glomerulus were investigated using
      the reverse-transcriptase polymerase chain reaction in SHR and WKY rats. Although
      there was no significant difference in PDGF B chain, TGF-beta, and Ang II
      receptors from the glomerulus were investigated using the reverse-transcriptase
      polymerase chain reaction in SHR and WKY rats. Although there was no significant
      difference in PDGF B chain, TGF-beta or Ang II receptor expression between SHR
      and WKY rats at the age of 7 weeks, the PDGF B chain expression of 16-week-old
      SHR was significantly higher (4.4-fold) than that of age-matched WKY rats. Next,
      we administered oral cilazapril at a dose of 10 mg/kg to 13-week-old SHR daily
      for 3 weeks. The systolic blood pressure in SHR treated with cilazapril was
      significantly lower than that in control SHR. After administration of cilazapril
      for 3 weeks, we examined the in vivo expression of growth factors and Ang II
      receptors in the glomerulus. The PDGF B chain expression was suppressed by
      treatment with cilazapril (2.5-fold) as compared with nontreated SHR. No
      alteration in TGF-beta or Ang II receptor expression was detected. We did not
      find any histological changes in the kidneys of SHR, WKY rats or cilazapril
      treated SHR, and cilazapril treatment did not suppress the glomerular size. These
      findings indicate that the expression of PDGF B chain in the glomerulus preceded
      the appearance of histological changes in SHR and that the administration of
      cilazapril inhibited the expression of PDGF B chain without affecting the
      glomerular size. This suggests that angiotensin I-converting enzyme inhibitors
      directly suppress the Ang II-induced PDGF B chain promotion in the glomerulus of
      SHR at the established hypertensive stage.

PMID- 8869082
TI  - Pyrene fluorescence: a potential tool for estimation of short-range lateral
      mobility in membranes of living renal epithelial cells.
AB  - The excimer-to-monomer (E/M) fluorescence ration of pyrene (p) and its
      derivatives has been found to correlate with membrane fluidity. We explored the
      possible use of this method in living renal epithelial cells. In Modin-Darby
      canine kidney cells, successful fluorescent labeling was obtained with p
      cholesterol, p-trimethylammonium (TMA), p-sulfonamidethyl-TMA, p-butyrate, p
      propanoate or p-dodecanoate. Among them, the labeling with p-cholesterol was most
      stable. The whole cell cholesterol content did not significantly increase after
      loading p-cholesterol and the probe incorporated was not degraded. The E/M ratio
      changed reproducibly and significantly by temperature change, a standard method
      to alter membrane fluidity. Thus, the E/M ratio of p-cholesterol fluorescence is
      suggested to be a potential parameter of membrane fluidity in living renal
      epithelial cells and might be useful in investigating the relationship between
      the physical state of the membrane and epithelial function.

PMID- 8869083
TI  - Inhibition of cGMP-phosphodiesterase restores the glomerular effects of atrial
      natriuretic factor in low sodium diet rats.
AB  - It was shown that atrial natriuretic factor (ANF)-induced increase in glomerular
      filtration rate (GFR) is blunted in low sodium diet. We investigated whether
      saralasin, as an angiotensin II receptor antagonist, or verapamil, as a calcium
      entry blocker, or theophylline and zaprinast, as inhibitors of cGMP
      phosphodiesterase activity, could restore the effect of ANF on GFR increase in
      low sodium diet rats. ANF alone (5 micrograms/kg bolus then 0.5 micrograms/min/kg
      BW maintenance) increased diuresis and natriuresis to the same extend in low and
      normal sodium diet rats but had no GFR-increasing effect in low sodium diet rats.
      Infusion of ANF in the presence of verapamil, saralasin, theophylline or
      zaprinast induced a significant increase in GFR and filtration fraction (FF).
      Administration of verapamil or saralasin alone did not alter GFR and FF whereas
      theophylline or zaprinast alone resulted in moderate but significant increases in
      both parameters. The increase of nephrogenous cGMP excretion in response to ANF
      infusion in low sodium diet rats was markedly lower as compared to normal sodium
      diet rats (243.4 +/- 43.3 vs. 444.0 +/- 35.6 pmol/min, respectively, p < 0.01).
      Administration of a selective inhibitor of cGMP-phosphodiesterase activity
      (zaprinast) abolished the differences in ANF-stimulated nephrogenous cGMP
      excretion in low and normal sodium diet rats. Basal and peak ANF (0.5 microM)
      stimulated cGMP formation by isolated glomeruli was significantly lower in low
      than normal sodium diet rats (1.4 +/- 0.1 vs. 2.9 +/- 0.2 and 7.1 +/- 0.5 vs.
      12.5 +/- 1.1 pmol/mg protein, for basal and ANF-stimulated cGMP formation,
      respectively; both p < 0.05). Zaprinast both alone and in combination with ANF,
      potentiated cGMP formation by glomeruli isolated from both groups of rats. In the
      presence of zaprinast, there were no differences in both basal and peak ANF
      stimulated cGMP formation by glomeruli isolated from low and normal sodium diet
      rats. cGMP-phosphodiesterase activity was the same in the medulla of both groups
      of rats but markedly higher in the renal cortex of low sodium diet rats as
      compared to normal sodium diet rats (82.6 +/- 6.0 vs. 59.8 +/- 4.3, respectively;
      p < 0.05). These data suggest that the lack of GFR-increasing response to ANF in
      low sodium diet rats is primarily due to the increase of cGMP hydrolysis in
      glomeruli.

PMID- 8869084
TI  - Multifrequency impedance in the assessment of body water losses during dialysis.

PMID- 8869085
TI  - Multiple primary cancers in population-based cancer registries.

PMID- 8869086
TI  - Health-related quality of life, cancer and health care.

PMID- 8869087
TI  - Cancer: a challenge for control theory and computer modelling.

PMID- 8869088
TI  - Obesity, social class and Western diet: a link to breast cancer prognosis.

PMID- 8869089
TI  - Continuing medical education in oncology in Europe.
AB  - A European Conference on Continuing Medical Education (CME) in Oncology was
      designed and organised in Dublin (Ireland), on 12th and 13th October 1995 by the
      European School of Oncology in collaboration with University College Dublin and
      with the financial support of the European Commission (Europe Against Cancer
      Programme). Two experts were invited from each Member State and all attended the
      Conference with the sole exception of the representatives of Luxembourg, who did
      not attend due to unexpected important commitments. Observers were invited to
      contribute to the discussion as representatives of organisations that were
      involved either directly or indirectly in CME. The Conference took the format of
      a plenary session coupled with the identification of five discussion groups
      formed to debate key areas in CME at a European level in oncology (Table 1). As a
      result of these discussions and subsequent consultations, an agreement was
      reached on the following statements: (a) Continuing Medical Education (CME) is an
      ethical duty and an individual responsibility for each doctor. Although CME
      should remain voluntary at the present time, it is nevertheless a professional
      obligation since almost 50% of medical knowledge becomes obsolete after ten
      years. It should be organised with clear guidelines for medical personnel working
      in hospitals, in primary health care and in private practice. (b) The CME system
      within the European Union (EU) should remain self-directed without the necessity
      for interval examinations: it should be interdisciplinary and must be driven and
      controlled by the profession itself. (c) A common concept and system within a CME
      framework may have a considerable impact on EU integration. It should certainly
      be developed, maintained and monitored at national level but on the basis of a
      common European model to ensure scientific and cultural interchange among Member
      States. (d) It was agree that a credit system is needed to help doctors keep
      track of their CME activities: the system should be based on the accumulation of
      credit points (one credit equalling one hour of continuing medical education) and
      monitored at a national level. Credit transfer among Member States is vital to
      facilitate exchange between Member States. (e) Oncology provides a very useful
      model of CME within which guidelines can be proposed and tested. Harmonisation of
      CME systems among the different European cancer organisations and scientific
      societies within this model system may represent a useful basis that other
      specialities can follow.

PMID- 8869090
TI  - Sex as a prognostic factor in gastric cancer.
AB  - The aim of this study was to assess whether survival of gastric cancer patients
      differed between males and females. Although it is well known that the incidence
      of gastric cancer is higher for men than for women, the existence of a sex
      specific prognosis has seldom been addressed. Studies based on population
      registries have not assessed the role of stage and histology. Cases of
      histologically confirmed gastric carcinoma were obtained from three Spanish
      hospitals in Soria (n = 405), Barcelona (n = 249) and Mataro (n = 197).
      Differences in possible confounders were tested between men and women and
      survival analyses were performed separately by hospital. Cox's proportional
      hazards models were used to account for age, tumour stage, histology and tumour
      sub-location. Only in Mataro was a significant difference in the stage
      distribution observed between women and men, with a lower proportion of local
      stage tumours among women (P = 0.047). No statistically significant differences
      of histological type between men and women were observed in any of the centres.
      After adjusting for tumour stage and age, women were observed to have
      significantly better survival in Barcelona (female to male hazard ratio (HR) =
      0.578, P < 0.001); this effect was marginal in Soria (HR = 0.788, P = 0.092) and
      non-significant in Matar-o (HR = 0.895, P = 0.54). Age-adjusted hazard ratios
      were calculated within each tumour stage. For Barcelona, the effect of better
      prognosis among women was most marked at local stage (HR = 0.320, P = 0.013), and
      in Soria at the regional stage (HR = 0.426, P = 0.002). Although in Mataro all
      HRs were below unity, none were statistically significant. Little effect was
      observed at the disseminated stage. The other covariables exerted no influence.
      Women appear to have a better prognosis than men, and the difference could be
      tumour stage dependent. Confirmation of these findings would give a valuable
      insight into gastric cancer growth and ultimately be of use in planning
      treatment.

PMID- 8869091
TI  - Results of a phase II trial of epirubicin and cisplatin (EP) before and after
      irradiation and 5-fluorouracil in locally advanced pancreatic cancer: an EORTC
      GITCCG study.
AB  - The objective of the present study was to define the role of chemotherapy, in the
      form of the EP regimen, consisting of epirubicin (E) and cisplatin (P) in
      addition to irradiation in combination with 5-fluorouracil (5-FU) for treatment
      of pancreatic cancer. 53 eligible patients with histologically or cytologically
      proven locally advanced pancreatic cancer were treated with three cycles of E 60
      mg/m2 (if this dose was well tolerated then the dose of E was increased by 10
      mg/m2 in the next cycle; 80 mg/m2 was the maximum dose for the following cycles)
      and P 100 mg/m2 once every 3 weeks, followed after 4 weeks by a split course of
      irradiation of 40 Gy with 5-FU 500 mg/m2 on each of the first 3 days of each 20
      Gy treatment segment. This was followed by another three cycles of EP in patients
      who achieved stable disease (SD) or a better response after the first three
      cycles. The treatment given with standard anti-emetics was moderately tolerated.
      The chemotherapy related toxicity consisted mainly of myelosuppression and the
      chemoradiotherapy related toxicity of gastrointestinal side-effects. However, due
      to the long duration of treatment which made the whole treatment difficult to
      endure, only 18/53 (34%) actually completed the full treatment regimen. Responses
      were evaluated after the first three cycles and 4 weeks after the completion of
      the treatment by serial CT-scans using standard criteria. The results in 53
      evaluable patients after the first three cycles of EP were as follows: 1 patient
      achieved a clinical complete response (CR), 7 a partial response (PR) (CR + PR:
      15%; 95% confidence interval (CI): 11-33%), 36 patients (68%) had stable disease
      (SD) and 6 patients progressive disease (PD). There was 1 early PD, 1 toxic death
      and 1 patient could not be evaluated. The response at the end of the treatment
      was 3 CR, 11 PR (CR + PR: 14/53 (26%); 95% CI: 15-40%), 30 SD and 6 PD. The
      median time to progression was 8.9 months and the median duration of response
      13.1 months. The median survival of all treated patients was 10.8 months (range 7
      days to 41.5 months), of responders 15.1 months and, of the patients with SD 10.3
      months. These results are comparable to other combined modality regimens reported
      in the literature for locally advanced disease. The addition of the systemic
      treatment with E and P offers no additional advantage to combined modality
      treatment alone.

PMID- 8869092
TI  - Feasibility of escalating daily doses of cisplatin in combination with
      accelerated radiotherapy in non-small cell lung cancer.
AB  - The aim of this study was to determine whether it is feasible to reduce the
      overall treatment time from 7 to 4 weeks in patients with non-small cell lung
      cancer (NSCLC) receiving radiotherapy with cisplatin. This follows an EORTC phase
      III randomised trial (08844) in which cisplatin given before each radiation dose
      resulted in improved local control and survival, but which had a relatively long
      treatment period of 7 weeks [Schaake-Koning et al., N Engl J Med 1992, 326, 524
      530]. 38 patients with confirmed NSCLC (2 stage I, 1 stage II, 18 stage IIIA, 17
      stage IIIB) received a total tumour dose of 55 Gy/20 fractions/26 days, from
      January 1992 to March 1994. Daily fractions of 2 Gy (5 times/week) were given to
      the macroscopic tumour and the non-involved adjacent lymph node areas. During the
      same session, a dose of 0.75 Gy was given to the macroscopic tumour (simultaneous
      boost). Cisplatin 6 mg/m2 was administered 1-2 h before each fraction, in an
      escalating total dose, during week 1 in 3 patients, during weeks 1 and 2 in 6
      patients, during weeks 1, 2 and 3 in 5 patients and during the whole treatment in
      24 patients. 38 patients were evaluable for acute side-effects (WHO). Maximal
      therapy-related toxicity (WHO) was grade 3 (nausea/vomiting in 2 patients,
      oesophagitis in 3 patients, dyspnoea in 3 patients, cough in 1 patient). Late
      side-effects were evaluated in 34 patients. There was grade 2 oesophagitis in 2
      patients; grade 3 toxicity in 8 patients (tiredness in 3 patients, dyspnoea in 3
      patients, oesophagitis in 2 patients); grade 4 toxicity in 4 patients (dyspnoea
      in 3 patients, cough in 1 patient). Pulmonary fibrosis grade 3 occurred in 4 and
      grade 4 in 6 patients. One patient developed a severe (grade 3) radiation
      pneumonitis. The low incidence of acute and late side-effects with this
      treatment, combining daily administration of 6 mg cisplatin with radical
      radiotherapy using a simultaneous boost technique, indicates that escalation of
      the radiation dose seems feasible.

PMID- 8869093
TI  - Neoadjuvant chemotherapy (MVAC) in locally invasive bladder cancer.
AB  - In order to evaluate the efficacy of neoadjuvant chemotherapy in invasive
      urothelial carcinoma of the bladder a retrospective analysis was performed. 54
      patients without distant metastases (T2-T3b, N0-X, M0) received 3 cycles of
      neoadjuvant chemotherapy according to the MVAC protocol (methotrexate,
      vinblastine, doxorubicin and cisplatin) after transurethral resection (TUR)
      followed by cystectomy. 52 patients had previously undergone cystectomy
      immediately after TUR. Complete histopathological remission was observed in 9
      patients (17.3%) after TUR and in 17 patients (31.5%) after TUR+MVAC. Neoadjuvant
      MVAC resulted, therefore, in a 14% higher rate of complete remissions. The
      overall response to TUR was significantly improved by MVAC therapy. Downstaging
      by neoadjuvant chemotherapy was more readily achieved in initially low-stage
      tumours (T2: 44.4% and 30.8%, T3a: 47.1% and 19%, T3b: 5.3% and 5.5% in patients
      receiving TUR+MVAC and TUR alone, respectively). Overall survival did not differ
      significantly between both groups. Patients who were successfully downstaged to
      pT0 had a significantly better prognosis, and patients resistant to chemotherapy
      had the poorest prognosis, showing the shortest survival. In conclusion,
      histopathological response at cystectomy was improved by neoadjuvant MVAC
      chemotherapy after TUR and can be expected to be prognostically relevant in those
      patients who can be downstaged to T0, although overall survival failed to be
      significantly increased in this relatively small patient sample.

PMID- 8869094
TI  - Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with
      benign and malignant breast tumours.
AB  - To investigate the clinical significance of an immune response to the MUC-1
      encoded polymorphic epithelial mucin (PEM) breast cancer, circulating immune
      complexes containing PEM (PEM.CIC) were measured in sera from 96 healthy women,
      in pretreatment serum samples from 40 patients with benign breast tumours and
      from 140 patients with breast cancer and in serum samples from 61 breast cancer
      patients with recurrent or progressive disease. PEM.CIC were measured using a
      sandwich enzyme-linked immunoassay, and PEM serum levels were measured with CA
      15.3 IRMA (Centocor Inc., Malvern, Pennsylvania, U.S.A.). Cut-off levels used for
      PEM.CIC and CA 15.3 were 120 Optical Density Units (O.D.) x 10(3) and 30 U/ml,
      respectively. In benign tumours, positivity for PEM.CIC was 37.5% (15/40). 36 of
      the 140 patients (25.7%) in the breast cancer pretreatment group had elevated
      PEM.CIC values. In patients with advanced metastatic disease, positivity for
      PEM.CIC was 18% (11/61). PEM.CIC was elevated in 32% (24/74) of node-negative
      patients, but only in 20% (12/59) of node-positive patients and absolute values
      were higher in node-negative patients (Mann-Whitney U test, two-tailed P =
      0.0168). There was an inverse correlation between positivity for PEM.CIC and
      extent of disease: while 3 of the 6 patients with a carcinoma in situ were
      positive, only 1 of the 15 patients with more than five nodes involved had
      elevated levels of PEM.CIC. All 7 patients with distant metastases at first
      diagnosis were PEM.CIC negative. 28 out of 133 patients had a recurrence during
      the observation period (median 55 months, range 27-84 months). 23 of these 28
      patients (82%) were PEM.CIC negative at the moment of first diagnosis. None of
      the patients with pretreatment elevation of both PEM.CIC and CA 15.3 (n = 13)
      relapsed. Our preliminary clinical results suggest that a humoral immune response
      to PEM protects against disease progression, and further support the idea of
      using synthetic peptides or glycopeptides containing the immunogenic core of the
      mucin as cancer vaccines.

PMID- 8869096
TI  - Is there a role for melatonin in the treatment of neoplastic cachexia?
AB  - It is known that neoplastic cachexia shows metabolic characteristics different
      from other common causes of malnutrition, and that it is mainly due to an
      abnormal secretion of TNF, whose levels are often high in patients with advanced
      neoplasia. Previous clinical studies have suggested that the pineal hormone
      melatonin (MLT), which plays an essential role in the neuroendocrine regulation
      of biological systems, may improve the clinical status of advanced cancer
      patients and inhibit TNF secretion. To investigate the relationship between MLT,
      TNF and cancer-related weight loss, 100 untreatable metastatic solid tumour
      patients entered this study to receive either supportive care alone, or
      supportive care plus MLT (20 mg/day orally in the evening). Patients were
      observed for 3 months, and were considered evaluable when they were observed for
      at least 2 months. There were 86 evaluable patients, the other 14 patients having
      died from rapid progression of disease. The per cent of weight loss greater than
      10% was significantly higher in patients treated by supportive care alone than in
      those concomitantly treated by MLT, with no difference in food intake (P < 0.01).
      Mean serum levels of TNF progressively increased in the supportive care group,
      but to levels that were not significantly different from pretreatment values. In
      contrast, TNF mean concentrations significantly decreased (P < 0.05) in patients
      concomitantly treated by MLT. These results suggest that the pineal hormone MLT
      may be effective in the treatment of the neoplastic cachexia by decreasing TNF
      blood concentrations.

PMID- 8869095
TI  - Early identification of neutropenic patients at risk of grampositive bacteraemia
      and the impact of empirical administration of vancomycin.
AB  - The aim of this multicentre randomised trial was to determine whether it was
      possible to predict grampositive bacteraemia, and whether the empirical use of
      vancomycin would lead to reduced morbidity and mortality. 35 of 113 patients
      (31%; confidence interval, CI 8.5), who presented with a skin or soft tissue
      infection and had received empirical vancomycin in addition to either ceftazidime
      or piperacillin-tobramycin, had initial bacteraemia with a single gram-positive
      bacterium compared with 135 of the 784 (17%; CI 2.6), who presented with another
      infection and who had been given ceftazidime or piperacillin-tobramycin without
      vancomycin (P < 0.001). Empirical vancomycin resulted in a higher rate of
      eradication (P = 0.033, relative risk 1.2), but not a better clinical outcome and
      was associated with more toxicity (P = 0.042, relative risk 1.6). Irrespective of
      the initial treatment regimen, fever lasted an average of 8 days, the empirical
      regimen was modified in more than 50% of cases and mortality attributed to gram
      positive infection was less than 2%. Incorporating vancomycin in the initial
      empirical antibiotic regimen for febrile neutropenic patients does not appear
      necessary, even for skin and soft tissue infections associated with gram-positive
      bacteraemia.

PMID- 8869097
TI  - Attitudes toward informing the cancer patient--a survey of Norwegian physicians.
AB  - To examine Norwegian physicians' attitudes to informing patients of a diagnosis
      of cancer, a random sample of 1467 were surveyed. The respondents rated their
      level of agreement to 14 statements, and the responses were analysed by chi
      squared statistics. 990 physicians responded (67%). Only 30.5% of the responding
      physicians had treated more than 10 cancer patients the previous year, which
      included 7.8% who had treated more than 50. 40.4% had treated none. The great
      majority (81%) preferred full information of the diagnosis. Physicians with
      increasing age preferred relatives not being present and gave priority to factual
      information and informing patients with the same diagnosis identically. Hospital
      physicians (39.5%) more often preferred other health professionals being present
      than physicians in private practice (18%) (P < 0.001). Number of cancer patients
      treated was not associated with attitudes toward the disclosure of information.
      Norwegian physicians prefer revealing the cancer diagnosis to patients, but have
      divergent opinions about how to do so. Some of these indicate suboptimal
      information-giving.

PMID- 8869098
TI  - Human papilloma virus has no prognostic significance in cervical carcinoma.
AB  - The prognostic significance of the detection of HPV (human papilloma virus) DNA
      in cervical carcinoma was evaluated in 223 cases treated from January 1988 to
      November 1989. HPV DNA was detected by PCR (polymerase chain reaction) on fresh
      tumour specimens obtained before therapy was started. HPV DNA of any type was
      detected in 93.3% of all tumours, HPV16 was the predominant type and was detected
      in 69% of cases. HPV18 was more frequent in adeno- and adenosquamous carcinoma
      than in squamous cell carcinoma and occurred more often in poorly differentiated
      tumours than in more highly differentiated tumours. Patients with HPV negative
      tumours were on average older than patients with tumours containing HPV. Neither
      presence of HPV DNA nor HPV type had prognostic significance. In 63 women with
      early stage tumours submitted to surgery, no difference was found in the
      frequency of lymph node metastasis, vessel invasion or prognosis related to HPV
      type. We conclude that neither the presence nor the type of HPV DNA had any
      prognostic significance in cervical carcinoma.

PMID- 8869099
TI  - Health-related quality of life of adults surviving malignancies in childhood.
AB  - While sophisticated data on specific problems are available, very little is known
      about the overall quality of life of long-term survivors of malignancies in
      childhood. We used a previously validated 15-dimensional questionnaire to examine
      the perceived health-related quality of life of 168 survivors, currently aged 16
      35 years, who had been treated for a malignancy at a single institution between
      1961 and 1993. All had been off therapy for at least 1 year (median, 12 years).
      In statistical terms, the quality of life score of the survivors was
      significantly better than that of 129 normal controls [0.966 versus 0.941
      (theoretical maximum 1), respectively; P < 0.001]; however, a difference of this
      magnitude is most likely not clinically significant. There were no associations
      between original diagnosis and present quality of life, but the numbers in each
      diagnostic group were small. The survivors reported significantly better levels
      of vitality, distress, depression, discomfort, elimination and sleeping
      dimensions than the controls. Although we are presently not able to identify all
      the contributing factors, we speculate that the high perceived quality of life of
      long-term survivors of childhood malignancies is at least in part a consequence
      of denial mechanisms which compensate or even overcompensate the objectively
      measurable late effects of childhood cancer.

PMID- 8869100
TI  - A new germline TP53 gene mutation in a family with Li-Fraumeni syndrome.
AB  - This report describes an unusual clinical presentation of Li-Fraumeni syndrome.
      Family history revealed a mild aggregation of adult cancers in one generation,
      and an unusual clustering of brain tumours of early childhood in the following
      generation. In order to evaluate the genetic basis for cancer predisposition in
      this family, molecular genetic analysis for the occurrence of germline TP53
      tumour suppressor gene mutations was performed on 12 siblings of two generations.
      Indirect mutation analysis was performed by the single-strand conformation
      polymorphism (SSCP) technique. Alterations were characterised by automated direct
      fluorescence sequencing analysis. Tumour material was also examined for p53
      protein accumulation by immunohistochemistry. Initially, a TP53 gene germline
      missense mutation was detected in an 11-year-old kindred with acute myeloid
      leukaemia (AML) following intensive treatment of a brain tumour. In peripheral
      blood and bone marrow samples of this proband, a reduction to hemizygosity
      occurred. During AML treatment, detection of LOH of 17p was used as a marker for
      clonality and treatment control. The mutation was found to be inherited from the
      proband's mother, who was diagnosed with breast cancer at the age of 48 years.
      Further, three siblings were carriers, and two are apparently healthy at the age
      of 21 and 23 years. Knowledge of germline mutations may allow accurate DNA-based
      carrier diagnosis which is of important clinical significance for treatment
      strategy and control. Furthermore, the occurrence of unaffected carriers in this
      family raises questions about appropriate methods of cancer surveillance and
      counselling for these people.

PMID- 8869101
TI  - Problems related to the coding of multiple primary cancers.
AB  - There is growing interest in multiple primary cancers (MPs), but the lack of a
      universally agreed definition can both modify the results for one series and
      hamper comparisons among cancer registries. The aim of this study was to compare
      agreement on the coding of MPs between two cancer registries, the Danish Cancer
      Registry and the Tuscany Tumour Registry, that adhere to different rules for
      accepting MPs, and to study whether coding according to common international
      rules (IACR) would increase the comparability. Data on 200 patients recorded as
      having more than one cancer were extracted at random from the two registers. The
      agreement on MP status between coders, one from each registry, using local rules
      and definitions on MP, was good (kappa value, 0.70). Exclusion of 11 expected
      discordant cases increased the agreement (kappa = 0.86). The agreement reached
      with the use of the IACR rules was very high (kappa = 0.80). We conclude that
      registries should present data according to international rules, in particular
      for the study of MPs. Registries should at least clearly indicate deviations from
      the agreed international standards, in order to facilitate comparisons on
      incidences.

PMID- 8869102
TI  - Immunoassays (ELISA) of urokinase-type plasminogen activator (uPA): report of an
      EORTC/BIOMED-1 workshop.
AB  - The urokinase-type plasminogen activator (uPA) is considered to play a key role
      in the process of invasion and metastasis. In several independent studies, in a
      variety of cancer types (e.g. of the breast, colon, stomach, lung, ovary), high
      antigen levels of uPA in tumour extracts have been associated with rapid disease
      progression. In these studies, different sets of antibodies and standards (often
      as commercially available uPA ELISA kits) have been used. The standards provided
      with the different uPA ELISA kits are different from each other in both
      composition and source. In addition, the different uPA ELISA kits use antibodies
      which differ in specificity and affinity for the various forms of uPA including
      pro-uPA, HMW-uPA, LMW-uPA, the aminoterminal fragment (ATF) and complexes with
      inhibitors (PAI-1 and PAI-2) and the receptor (uPAR). Further, the composition of
      tumour tissue extraction buffers differ significantly among the published
      studies. Thus, it is not surprising that the ranges of cytosolic uPA levels
      reported differ considerably even when measured within the same tumour type.
      These discrepancies led the EORTC Receptor and Biomarker Study Group, in
      conjunction with the BIOMED-1 consortium on 'Clinical Relevance of Proteases in
      Tumour Invasion and Metastasis', to organise a workshop to study the
      characteristics associated with six different uPA immunoassays (ELISA) used in
      clinical studies reported in the literature. Although the absolute uPA antigen
      values measured with the respective uPA ELISA kits differed, high correlations
      were obtained for any two of the four uPA ELISA kits finally applied to sets of
      breast cancer cytosol preparations. The preparations used at present as standards
      in the various uPA ELISA kits are not representative of actual human breast
      cancer cytosols. Thus absolute standardisation is only possible by using a common
      reference sample (breast cancer cytosol) and similarly composed ELISA uPA kits.
      Then it will be possible to generate comparable data on clinical tissue as well
      as to check for batch-to-batch variations within particular ELISA kits.

PMID- 8869103
TI  - Relationship between the tumour tissue pharmacokinetics and the antiproliferative
      effects of anthracyclines and their metabolites.
AB  - The intrinsic activity of anthracyclines and their metabolites was measured in
      order to determine whether the tumour exposure to the compounds reflects the
      difference in their ability to inhibit tumour growth. (Dox), 4'-epidoxorubicin
      (Epi-Dox), daunorubicin (Dauno), N-1-leucyl-doxorubicin (Leu-Dox) and their
      metabolites were analysed for their antiproliferative effects in three human
      malignant cell lines: MCF7, RPMI 8226 and A2780. The antitumour efficacy of
      equitoxic, maximum tolerated doses of the present drugs was assessed in nude mice
      bearing subcutaneous (s.c.) well-established A2780 doses of the parent drugs was
      assessed in nude mice bearing subcutaneous (s.c.) well-established A2780 human
      ovarian cancer xenografts. The same doses were given to tumour-bearing mice to
      determine the distribution of the anthracyclines and their metabolites in A2780
      tumour tissue during the first 48 h after injection. In vitro antiproliferative
      effects of the anthracyclines and their metabolites revealed a comparable
      activity for the parent drugs and daunorubicinol, whereas the other metabolites
      were at least 10-fold less active. The growth inhibition obtained in A2780
      xenografts was 87% for Dox, 82% for Epi-Dox, 74% for Dauno and 97% for Leu-Dox.
      In vivo, the exposure of tumour tissue to the drug, calculated as the area under
      the concentration-time curve (AUC), was related to the extent of growth
      inhibition after correction of the AUC values for the intrinsic activity of the
      anthracycline. For each of the anthracyclines, the sum of the corrected AUC
      values (nmol/g/min) of the active compounds was calculated as 8812 for Dauno;
      9320 for Epi-Dox; 10 986 for Dox and 15 163 for Leu-Dox. The sequence of
      increasing AUC values corresponded with the sequence of increasing growth
      inhibition by the four anthracyclines observed in A2780 xenografts.

PMID- 8869104
TI  - p53 expression, DNA content and cell proliferation in primary and synchronous
      metastatic lesions from ovarian surface epithelial-stromal tumours.
AB  - The aim of this study was to investigate biological heterogeneity between primary
      and metastatic ovarian cancer lesions from individual patients as a means of
      elucidating steps in clinical progression. Cancer tissue from 61 untreated
      patients with ovarian surface epithelial-stromal tumours was examined. p53
      expression detected immunocytochemically by the PAb1801 antibody, DNA content
      evaluated by flow cytometry, and cell proliferation evaluated as the
      [3H]thymidine labelling index were investigated in primary tumours and
      corresponding synchronous metastases. The frequency of p53 positivity was similar
      in primary (62%) and metastatic (66%) sites, with an agreement between the two
      lesions from the same patient in 97% of the cases. Similarly, aneuploidy
      frequency (80%) and DNA indices were superimposable in primary and metastatic
      lesions from the same patient, with a 94% agreement. The frequency of aneuploidy
      was higher in p53-positive than in p53-negative lesions. An overall poor
      agreement (rs = 0.44) was observed for proliferative activity of primary and
      metastatic lesions, due to a heterogeneous profile in omental with respect to
      primary tumours, which was mainly evident in p53-positive cancers. Conversely,
      cell proliferation of peritoneal, abdominal and pelvic lesions was qualitatively
      similar to that of the primary tumour in 88% of patients.

PMID- 8869105
TI  - Expression of CD44 isoforms in human skin cancer.
AB  - In animal models, isoforms of CD44 (CD44v) containing sequences encoded by one or
      several of ten different exons (v1-v10) contribute to tumour metastasis. In
      certain human cancers, CD44v6 expression is associated with poor prognosis. This
      paper examines CD44v expression in skin carcinogenesis and skin cancer
      metastasis. CD44v expression was studied in basal cell carcinoma (BCC), squamous
      cell carcinoma (SCC), primary malignant melanoma (PMM), metastases of MM (MMM),
      benign melanocytic naevi (BMN) and normal skin (NS) by immunohistochemistry and
      reverse transcript polymerase chain reaction (RT-PCR). BCC, SCC and NS expressed
      several CD44v, including v6, albeit in different distributions and intensities.
      PMM, MMM and BMN expressed isoforms containing v7/8 and v10, but failed to
      express epitopes encoded by v5 or v6. Thus, different CD44 isoforms are found in
      human skin cancers and are modulated during carcinogenesis. However, we did not
      observe a correlation of CD44v6 expression with metastatic potential.

PMID- 8869106
TI  - Augmented expression of LCK message directed from the downstream promoter in
      human colorectal cancer specimens.
AB  - Lck protein is expressed in some colon carcinoma cell lines but its expression in
      colon cancer cells in vivo has not been clarified. LCK transcription is regulated
      from two distinct promoters and initiated exclusively from the downstream
      promoter in colon carcinoma cell lines in contrast to peripheral lymphocytes. We
      investigated the expression of the downstream promoter-initiated LCK transcript
      in 18 colorectal primary cancer and normal mucosae, and two hepatic metastases,
      using a RNase protection assay with the EcoRI-BglII fragment of human LCK cDNA,
      YT16. In normal tissues, only traces of the LCK transcript were detected. The
      expression of the LCK transcript was augmented in 3/18 cancer specimens. The
      relative level of the LCK transcript in the cancer tissue compared to the average
      value of normal adjacent tissue was 10-60 in 3 cases, and 3-10 in 7 cases. One
      hepatic metastasis expressed more LCK message than the primary lesion. Our
      results indicate that the LCK message is strongly expressed in some colorectal
      cancers.

PMID- 8869107
TI  - Tumour cell vaccines that secrete interleukin-2 (IL-2) and interferon gamma (IFN
      gamma) are recognised by T cells while resisting destruction by natural killer
      (NK) cells.
AB  - The inoculation into mice of genetically engineered tumour cells that secrete IL
      2 or IFN gamma results in rejection, while unmodified parental tumour cells grow
      progressively. In vivo studies demonstrated synergy between IL-2 and IFN gamma
      leading to the rejection of the transduced tumour cells. IL-2 is required for T
      cell proliferation and differentiation. IFN gamma induced the upregulation of MHC
      class I molecules that present peptides to CD8+ T cells. Furthermore, IFN gamma
      can correct defects in antigen processing. Thus, for T cells, IL-2/IFN gamma
      secreting double cytokine tumour cell vaccines might serve as class I+
      peptide/antigen presenting depots for developing effector cells. In contrast to T
      cells, NK cells exert spontaneous killing and kill class I+ targets less well
      than those that are class I-. For this reason, they may actually have a
      detrimental effect by destroying a class I+ tumour cell vaccine before adequate T
      cell stimulation occurs. Based upon this rationale, we tested the hypothesis that
      an unrecognised benefit of increased class I expression by tumour cells in
      response to IFN gamma secretion would be to enable cytokine-secreting vaccine
      cells to resist destruction by NK cells. Our results demonstrated that T cells
      recognised tumour cells secreting IFN gamma better than those secreting IL-2. NK
      cells, in contrast, were inhibited by tumour cells that secreted IFN gamma, but
      not by those that secreted IL-2. The findings suggest that, in addition to
      upregulating adhesion molecules, MHC molecules, and correcting defects in antigen
      presentation pathways, IFN gamma secretion may protect tumour cell vaccines from
      early NK-mediated destruction, keeping them available for T cell priming.

PMID- 8869108
TI  - Tumour growth and fetal uptake of amino acids in the pregnant rat.
AB  - The aim of the present investigation was to determine the effects of maternal
      tumour burden on fetal growth and to relate them to amino acid availability to
      the fetus. A fast-growing tumour, the Yoshida AH-130 ascites hepatoma, was
      inoculated into rats during pregnancy. Late pregnant rats bearing a rapidly
      growing tumour presented a normal conceptus mass while the tumour cell content
      was unaffected by gestation. In addition, no changes were found in fetal uptake
      of amino acids as measured by the fetal accumulation of [14C]aminoisobutyrate and
      [14C] cycloleucine. However, increased alanine and leucine concentrations in the
      fetal circulation of the tumour-bearing rats suggest an enhanced fetal amino acid
      availability which does not seem to be the result of changes in placental or
      fetal relative blood flow, as indicated by the tissue accumulation of [14C]DDT,
      which were actually lower in the tumour-bearing rats. It may be suggested that
      tumour burden induces changes in placental amino acid transport systems.

PMID- 8869109
TI  - In vitro induction of differentiation by ginsenoides in F9 teratocarcinoma cells.
AB  - The aim of this study was to determine the ability of the ginsenosides, extracts
      of Panax ginseng C.A. Meyer, to cause differentiation of F9 teratocarcinoma stem
      cells as a model system. F9 stem cells cultured in the presence of the
      ginsenosides together with dibutyryl cyclic AMP (dbcAMP) became parietal endoderm
      like cells. Moreover, the expression of differentiation marker genes, such as
      laminin B1 and type IV collagen, was increased after treatment with the
      ginsenosides. Among the various purified ginsenosides, Rh1 and Rh2 were the most
      effective at causing differentiation of F9 cells. Since ginsenosides and
      glucocorticoid hormone have similar chemical structures, we examined the
      possibility of the involvement of a glucocorticoid receptor (GR) in the
      differentiation process induced by the ginsenosides. According to Southwestern
      blot analysis, a 94 kDa protein regarded as a GR was detected in F9 cells
      cultured in the medium containing the ginsenosides Rh1 or Rh2. In addition, F9
      stem cells treated with the ginsenosides Rh1 or Rh2 and with RU486, a
      glucocorticoid antagonist with a high affinity for the GR, did not differentiate
      into endoderm cells morphologically, and the expression of laminin B1 gene was
      not induced in these cells. In a gel mobility shift assay, protein factors
      capable of binding to the glucocorticoid responsive element (GRE) specifically
      were detected in nuclear extracts of the ginsenoside-treated F9 cells. Moreover,
      overexpression of GR by cotransfection of GR expression vector and GRE-luciferase
      vector enhanced the transactivation activity of GRE promoter in the presence of
      ginsenosides Rh1 or Rh2 and was further augmented by dbcAMP. In addition,
      ginsenosides Rh1 and Rh2 bound to a GR assessed by whole-cell binding assay, even
      though the specific binding affinity was weaker compared to dexamethasone. Based
      on these data, we suggest that the ginsenosides Rh1 and Rh2 cause the
      differentiation of F9 cells and the effects of ginsenosides might be exerted via
      binding with a GR or its analogous nuclear receptor.

PMID- 8869110
TI  - Somatostatin receptor imaging in small cell lung cancer.
AB  - To determine its usefulness, we evaluated 111In-DTPA-Octreotide (octreotide
      scintigraphy) in the initial staging of 19 patients with histologically proven
      small cell lung cancer (SCLC) and compared the results to those of conventional
      imaging. Images performed during initial staging demonstrated 21 known pulmonary
      lesions and two known supraclavicular nodes. We detected a previously unknown
      mediastinal lesion. The number of metastases was underestimated, with no liver
      (5), brain (1) or skin metastases detected. Bone lesions were identified in 4 out
      of 5 patients. There were fewer lesions detected with octreotide scintigraphy
      than with bone scintigraphy (except for one case). We therefore conclude that
      octreotide scintigraphy is a highly effective method for detecting SCLC primary
      tumour and supraclavicular nodes; the procedure is of limited value for distant
      metastasis. Further studies are needed to establish its ability for detecting
      residual intrathoracic disease, and confirm the value of octreotide scintigraphy
      in differentiating residual disease from other benign lesions.

PMID- 8869111
TI  - Fotemustine in patients with advanced gastric cancer, a phase II trial from the
      EORTC-GITCCG (European Organization for Research and Treatment of Cancer,
      Gastrointestinal Tract Cancer Cooperative Group).
AB  - Fotemustine activity was evaluated in 26 patients, mostly pretreated, with
      advanced gastric cancer. Its main toxicity was haematological with grade 3-4
      neutropenia in 32% and grade 3-4 thrombocytopenia in 50% of the patients,
      complicated by 2 toxicity-related deaths due to haemorrhage. No complete or
      partial responses were observed in the 26 eligible patients and median survival
      was only 11 weeks. Fotemustine therefore has no activity in advanced gastric
      cancer.

PMID- 8869112
TI  - Prostate cancer. An insight into screening and local treatment.

PMID- 8869113
TI  - Male breast cancer: statistical and clinical data for the Maltese population.

PMID- 8869114
TI  - High-dose recombinant interleukin-2/verapamil combination in advanced cancer.

PMID- 8869115
TI  - Activity of gemcitabine in platinum-resistant ovarian germ cell cancer.

PMID- 8869116
TI  - Pharmacological agents for stress testing in the diagnosis of coronary artery
      disease.
AB  - Non-invasive diagnosis of coronary artery disease is based on the combined use of
      a technique capable of identifying accurately the presence of ischaemia and a
      stress capable of safely inducing myocardial ischaemia. In the last few years
      great progress has been made in this field thanks to the use (a) of cardiac
      imaging techniques that clearly depict the presence and extent of myocardial
      ischaemia and to (b) the introduction of stresses other than exercise. These
      stresses are mainly pharmacological and are particularly useful in patients
      unable to exercise or who cannot exercise to a level considered adequate for
      diagnostic purposes. These alternative stress procedures are particularly useful
      when dealing with echocardiography since exercise usually prevents the
      acquisition of images of sufficient quality to be considered diagnostic.

PMID- 8869117
TI  - Optimal pharmacological stress testing for the diagnosis of coronary artery
      disease: a probabilistic approach.
AB  - Previous reports have suggested that dobutamine stress echocardiography compares
      favourably with other stress agent-imaging modality combinations for the
      detection of coronary artery disease. However, in daily clinical practice the
      value of a test is defined on a probability basis. To study the relative
      diagnostic contribution of clinical and dobutamine stress test variables,
      Bayesian analysis was performed in 223 patients with suspected coronary artery
      disease, who underwent coronary angiography and a high-dose dobutamine stress
      test in conjunction with electrocardiography, echocardiography and Technetium-99m
      sestamibi SPECT myocardial perfusion scintigraphy. According to the pre-test
      (clinical) probabilities, patients were divided into low-, intermediate- and high
      risk groups; 155 patients were in the intermediate-risk group. After dobutamine
      stress echocardiography the number of patients in this intermediate-risk group
      was reduced to 102 (P < 0.0001). This reduction of patients in the intermediate
      risk group by echocardiography was better than perfusion scintigraphy (102 vs 126
      patients, P < 0.05) or classic markers of ischaemia such as angina and/or ST
      segment changes (102 vs 150, P < 0.0001). Moreover, there was a good correlation
      between the echocardiographic post-test probabilities and the true distribution
      of coronary artery disease.

PMID- 8869118
TI  - Functional evaluation of patients with coronary artery disease: selection of
      appropriate pharmacologic agents and imaging modalities.
AB  - Exercise myocardial perfusion imaging and exercise echocardiography have been
      applied widely for diagnosis and risk stratification of patients with known or
      suspected coronary artery disease. The accuracy of these evaluations depends upon
      the ability of the patient to achieve maximal exercise (> 85% of age-predicted
      maximal heart rate). In patients unable to exercise or with a limited capacity to
      exercise maximally, pharmacologic stress imaging is a safe and effective
      alternative to exercise stress imaging. Pharmacologic stress is also indicated in
      patients with resting or exercise-induced left bundle branch block. Vasodilator
      stress with dipyridamole or adenosine, as well as catecholamine stimulation with
      dobutamine or preliminarily with arbutamine, provides diagnostic and prognostic
      information that appears to be equivalent to that achieved with exercise imaging.
      In addition, low dose catecholamine infusion during echocardiography to assess
      inotropic reserve is valuable in identifying viable myocardium in patients with
      left ventricular dysfunction and appears to assess viability with an accuracy
      that approaches that of nuclear cardiology methods. Hence, pharmacologic stress
      imaging, like exercise stress imaging, has important implications regarding
      patient outcome, patient management, and selection of patients for interventional
      therapy.

PMID- 8869119
TI  - Dobutamine echocardiography for determining myocardial viability after
      reperfusion: experimental and clinical observations.
AB  - Dobutamine echocardiography is being used increasingly to assess the presence of
      viable myocardium after reperfusion therapy in patients with myocardial
      infarction. This review places emphasis on results of experimental and pertinent
      clinical studies in order to provide an understanding of the physiologic basis
      for using this modality for detecting viable myocardium. It is hoped that an
      understanding of these principles will allow a more meaningful interpretation of
      test results in different clinical situations.

PMID- 8869121
TI  - Pharmacological stress testing and imaging: concluding remarks.

PMID- 8869120
TI  - Clinical and diagnostic utility of arbutamine for cardiovascular stress testing
      during echocardiographic monitoring.
AB  - Arbutamine (Gensia, Inc., San Diego, CA) is a newly-developed sympathomimetic
      agent specifically designed for cardiovascular stress testing. It has been
      successfully used for the detection of coronary artery disease in conjunction
      with electrocardiography, echocardiographic and radionuclide techniques.
      Arbutamine increases heart rate and contractility, thus provoking ischaemia in a
      manner analogous to that of physical exercise. Ischaemia becomes manifest by
      reproduction of typical angina, diagnostic electrocardiographic changes, the
      development of a wall motion abnormality on two-dimensional echocardiography or
      of a perfusion defect on thallium scintigraphy. Thus far in clinical trials it
      has shown an acceptable side-effect profile and a level of diagnostic accuracy
      for the detection of patients with coronary disease equivalent to or exceeding
      that seen with physical exercise.

PMID- 8869122
TI  - Study on the isentropic equations of nucleotide sequences and their application.
AB  - The tetrahedral representation of DNA sequences and its applications have been
      studied by many authors. In this paper we study the isentropic equations of DNA
      sequences and their application. First, the DNA sequence entropy is introduced,
      and the entropy current and divergence are defined. Second, the isentropic
      equations are deduced and the isentropic curves on the three coordinate planes
      are respectively drawn by a computer. Third, an analysis is given on the entropy
      distribution on the coordinate planes. Finally, we make use of the results to
      discuss the relationship of the fastest increasing directions of the entropy for
      the cytochrome c genes of seven species.

PMID- 8869123
TI  - Spatial pattern formation during aggregation of the slime mould Dictyostelium
      discoideum.
AB  - Stream formation and spiral wave behaviour during the aggregation of
      Dictyostelium discoideum (Dd) are studied in a model based on the Martiel
      Goldbeter equations for cAMP relay, combined with chemotactic motion of Dd cells.
      The results show that stream formation occurs if the turnover rate of
      intracellular cAMP is increased. This increase in the turnover rate of cAMP[in]
      leads to a dependence of the speed of the cAMP wave on the cell density. We
      propose that this dependence of wave speed on cell density is the underlying
      mechanism for stream formation. Besides stream formation, increasing the turnover
      rate of cAMP[in] also results in a spiral wave period that decreases during
      aggregation, a phenomenon that is commonly observed in situ. Furthermore, the
      dependence of wave speed on cell density is measured empirically. The speed of
      the cAMP wave is found to decrease as the wave travels from high to low cell
      density. This indicates that in situ, wave speed does depend on cell density.

PMID- 8869124
TI  - Exploring the mechanisms of primary antibody responses to T cell-dependent
      antigens.
AB  - We have developed a model of the early events that occur during a primary
      antibody response to a T cell-dependent antigen. Within secondary lymphoid
      organs, B cell proliferation in response to antigen injection gives rise to two
      kinds of transient structures: foci that develop in the T cell area, and germinal
      centers, that develop in the secondary follicles of the B cell area. Foci give
      rise to plasma cells that are responsible for the majority of early circulating
      antibody, whereas germinal centers are sites of somatic mutation and memory cell
      formation. Here we model the cell-cell interactions and cell population kinetics
      involved in the generation of antibody-forming cell foci, and compare our model
      with experimental data. We focus on fundamental issues involving the control of B
      cell proliferation and differentiation, using simple kinetic models that depend
      on direct cell-cell interactions and on the action of cytokines. We show that
      with realistic parameter assumptions our model can account for both the rapid
      cellular expansion and the differentiation of B cells into antibody-secreting
      cells. By summing the expected antibody production of all the plasmablasts and
      plasma cells that are generated during the focus response we can account for much
      of the antibody observed in the serum of mice during a primary response. Lastly,
      we compare the predictions of our model for two different scenarios for the
      control of B cell proliferation. In one model, we assume that B cells, once
      activated, proliferate under the control of cytokines without direct interaction
      with activated T cells. In the other model, we assume that after dividing B cells
      return to rest and require a contact-dependent signal from an activated T cell to
      divide again. The first model gives rise to large foci and antibody levels
      similar to that observed in experiment, whereas the latter model gives rise to
      four-fold smaller foci and to circulating antibody levels that are one order of
      magnitude lower than typical experimental values. This result suggests that B
      cells may be able to divide without further contact with T cells once a cognate
      interaction has occurred.

PMID- 8869125
TI  - A possible role for plasmids in mediating the cell-cell proximity required for
      gene flux.
AB  - One of the major requirements for successful gene flux is a close proximity
      between participating organisms. In previous articles, we have proposed that
      plasmids act as powerful vehicles transporting genes collected by integration and
      transposition, mainly via the process of conjugation. However, in addition to
      conjugation, there are other processes, also mediated by plasmids, in which
      different cells come into very close contact with each other, such as symbiosis
      and the formation of multi-specific cellular communities. There is evidence that
      suggests that such intimate associations between cells may facilitate gene
      transfer events, even between distantly related organisms. Examples of symbiotic
      endosymbiotic, and parasitic associations provide evidence in support of the role
      of plasmids in bridging the genetic gap between species. In this purely
      theoretical article we attempt to conceptualize existing data on this subject,
      provide new insights and present testable predictions on how plasmids may
      facilitate gene flux by bringing cells together.

PMID- 8869126
TI  - Ion currents underlying sinoatrial node pacemaker activity: a new single cell
      mathematical model.
AB  - The ionic currents underlying autorhythmicity of the mammalian sinoatrial node
      and their wider contribution to each phase of the action potential have been
      investigated in this study using a new single cell mathematical model. The new
      model provides a review and update of existing formulations of sinoatrial node
      membrane currents, derived from a wide range of electrophysiological data
      available in the literature. Simulations of spontaneous activity suggest that the
      dominant mechanism underlying pacemaker depolarisation is the inward background
      Na+ current, ib,Na. In contrast to previous models, the decay of the delayed
      rectifying K+ current, iK, was insignificant during this phase. Despite the
      presence of a pseudo-outward background current throughout the pacemaker range of
      potentials (Na-K pump+leak currents), the hyperpolarisation-activated current
      i(f) was not essential to pacemaker activity. A closer inspection of the current
      voltage characteristics of the model revealed that the "instantaneous" time
      independent current was inward for holding potentials in the pacemaker range,
      which rapidly became outward within 2 ms due to the inactivation of the L-type
      Ca2+ current, iCa,L. This suggests that reports in the literature in which the
      net background current is outward throughout the pacemaker range of potentials
      may be exaggerated. The magnitudes of the action potential overshoot and the
      maximum diastolic potential were determined largely by the reversal potentials of
      iCa,L and iK respectively. The action potential was sustained by the incomplete
      deactivation of iCa,L and the Na-Ca exchanger, iNaCa. Despite the incorporation
      of "square-root" activation by [K]o of all K+ currents, the model was unable to
      correctly simulate the response to elevated [K]o.

PMID- 8869127
TI  - Rational design of receptor partial agonists and possible mechanisms of receptor
      partial activation: a theory.
AB  - Partial activation of membrane receptors using specific partial agonists may be
      particularly beneficial to the treatment of some chronic diseases like congestive
      heart failure, because receptor partial activation usually avoids overstimulation
      and also minimizes desensitization. At present, partial agonists are obtained
      almost exclusively by screening numerous newly-synthesized compounds, and little
      is known about the rational design of partial agonists with desired potencies and
      maximum activities. It is proposed in this study that a proper covalent
      attachment of a receptor full agonist to an antagonist (competitive or non
      competitive) of the same receptor type may form a hybrid compound with a reduced
      maximum activity. In theory, the potency (EC50 value) and the reduced maximum
      activity of such an agonist-antagonist hybrid are predictable, based on the
      receptor binding affinities of the incorporated agonist and antagonist. The
      agonist-noncompetitive antagonist hybrids produce bell-shaped concentration
      response curves, whereas the agonist-competitive antagonist hybrids produce
      concentration-response curves with reduced but plateaued maximum responses. The
      agonist-competitive antagonist hybrids can be very useful for therapeutic
      purposes because they enable us to stably activate a specific type of receptor at
      desired submaximal set-points. In this study, it is postulated that some partial
      agonists may also contain both agonistic and antagonistic moieties, analogous to
      the proposed hybrid compounds. This hypothesis is supported by data from modeling
      studies showing that several unique pharmacological characteristics of known
      partial agonists exactly match the projected features of the agonist-antagonist
      hybrid compounds. Modeling studies based on the hybrid compound model also
      explain why the reduced maximum response elicited by some partial agonists can be
      increased or even fully restored in the presence of spare receptors. As indicated
      by modeling studies, a reduced maximum activation of receptors may, at least in
      some cases, not result from a partial activation of each individual receptor
      being occupied by the partial agonist, but rather may be due to a reduced maximal
      receptor occupancy by the agonistic moiety in the co-presence of an antagonistic
      moiety. The agonist-antagonist hybrid proposed in this study not only enhances
      our understanding of the possible structural requirements and rational design of
      receptor partial agonists, but it also enhances our understanding of the possible
      molecular basis of receptor partial activation. This new model also provides an
      alternative mathematical framework for modeling partial agonist data.

PMID- 8869128
TI  - Centromeric locations in karyotypes: a rule derived from the theory of branched
      polymers.
AB  - It is believed that chromosomes occupy non-overlapping domains in the interphase
      nucleus, and that the nuclear volume can be divided into the interchromosomal
      space and the chromosome domains. Concentrations of various components (e.g.,
      small ions) are different in these compartments. Since nuclear volume is twice as
      large in G2 as in G1 phase, V2/V1 (the G2/G1 ratio of total chromosomal volumes)
      must be two in order to keep the interchromosomal concentrations unchanged. The
      aim of this study is to test the 'V2/V1 = 2' hypothesis. It has been shown that
      G1-chromosomes behave as real flexible polymers. If a G2-chromosome behaves as a
      four-arm star-type branched polymer, then, according to polymer theory, its
      chromosome volume should depend on its centromere position. We calculated V2/V1
      values for 40 karyotypes, from yeast to human, and 19 of them have V2/V1 = 2 +/-
      10%. There are two types of exceptions from the 'V2/V1 = 2' rule: karyotypes with
      a large number of telocentric chromosomes (V2/V1 > 2), and karyotypes with a
      large number of metacentric chromosomes (V2/V1 < 2). It has been observed in the
      literature that for all-telocentric karyotypes of mouse and Chinese muntjac,
      their chromosomes form branch-like structures by association of centromeres in
      clusters in G2 phase. When calculated for these temporary structures, V2/V1
      decreases to two if the number of associated chromosomes per cluster is greater
      than or equal to five. This corresponds to a number of centromere clusters per
      nucleus less than or equal to 8-9 for mouse and Chinese muntjac, which is
      consistent with observation. For rye, all-metacentric karyotype, the calculated
      V2/V1 value increases to nearly two if B-chromosomes are taken into account.

PMID- 8869129
TI  - The role of ACE inhibitors in preventing myocardial infarction: potential
      mechanisms and clinical implications.

PMID- 8869130
TI  - Maintenance of vascular integrity: role of nitric oxide and other bradykinin
      mediators.
AB  - In the blood-vessel wall, the endothelium plays a key functional role by
      generating several substances that modulate vascular smooth muscle tone, as well
      as growth, and platelet function. This review focuses on the role of the
      endothelial L-arginine/nitric oxide signal transduction pathway in the
      maintenance of vascular integrity. Functional alterations of this pathway may be
      important in cardiovascular disease, because depressed activity of this
      protective mechanism leads to impaired relaxation and is also associated with
      reduced antithrombotic properties of the endothelial layer. Many of the
      beneficial effects of ACE inhibitor therapy may be mediated through their ability
      to enhance the physiological roles of nitric oxide.

PMID- 8869131
TI  - Angiotensin I converting enzyme gene polymorphism and coronary heart disease.
AB  - Genetic variations in the renin-angiotensin and kallikrein-kinin systems could
      prove to be significant pathophysiological mechanisms affecting coronary heart
      disease (CHD), particularly given the powerful vasoactivity of products such as
      angiotensin II and bradykinin. Indeed, studies show that angiotensin converting
      enzyme (ACE) gene polymorphism is associated with an increased risk of myocardial
      infarction and death, even in otherwise low-risk subjects. Genetic differences do
      not appear to be a risk factor for atherosclerosis or hypertension, however.
      Because ACE polymorphism modulates local production of angiotensin II, a powerful
      coronary vasoconstrictor, it may influence left ventricular mass in general as
      well as in coexisting disease states such as hypertension and cardiomyopathy.
      However, further study is needed to clarify the implications of ACE polymorphism
      in patients with left ventricular hypertrophy. Interactions between ACE and
      angiotensin II type-1 receptors may have clinical implications for preventing and
      managing CHD. Screening for genetic risk, as evidenced by certain variants in
      receptor coding sequence, may prove worthwhile if detrimental effects can be
      countered by drugs such as ACE inhibitors and angiotensin II receptor blockers.
      Given the important roles of angiotensin II and bradykinin as modulators of
      cellular growth and of vasoactivity, deleterious and beneficial effect at
      different stages of the atherosclerotic process and during acute events leading
      to myocardial infarction or sudden death can be suspected.

PMID- 8869132
TI  - The role of genetic variants in angiotensin I converting enzyme, angiotensinogen
      and the angiotensin II type-1 receptor in the pathophysiology of heart muscle
      disease.
AB  - The cardiac vasculature and myocardium contain components of the renin
      angiotensin system (RAS), which may regulate local growth and cellular function.
      Alterations in the expression or action of these components, which include
      angiotensin converting enzyme (ACE), angiotensinogen, and angiotensin II type-1
      receptors, may contribute to the development of disease, such as hypertension,
      left ventricular hypertrophy, myocardial infarction, and end-stage heart failure.
      ACE is one RAS component found to have genetic variants associated with
      cardiovascular disease. Molecular variants in any of the RAS components may
      affect signalling pathways, possibly increasing the risk of heart failure. In
      addition, variants may exacerbate the deleterious effects of altered RAS
      expression on cardiac function. Genetic variation in RAS components may affect
      therapy with ACE inhibitors and receptor-blocking agents. Although at present
      there is no compelling reason to target molecular variations for treatment, a new
      era in selective pharmacological therapy for cardiovascular disease may be
      imminent.

PMID- 8869133
TI  - Role of the fibrinolytic system in preventing myocardial infarction.
AB  - Activation of the renin-angiotensin system (RAS) has been implicated in the
      pathogenesis of acute myocardial infarction (AMI). Similarly, reduced
      fibrinolytic activity has been associated with an increased risk of AMI. Evidence
      is now accumulating that the RAS plays an important role in the regulation of
      fibrinolysis and that pharmacological interruption of the RAS exerts a positive
      effect on endogenous fibrinolytic balance. This relationship appears to provide a
      partial explanation for the newly recognized effect of angiotensin converting
      enzyme inhibitors in preventing AMI.

PMID- 8869134
TI  - Anti-adrenergic effects of angiotensin converting enzyme inhibitors.
AB  - The renin-angiotensin and adrenergic nervous systems are cross-regulated
      compensatory mechanisms that are induced or activated in the failing heart. In
      ventricular myocardium, the activation of one of these systems leads to
      activation or induction of the other, resulting in co-amplification of cellular
      mechanisms that result in cardiac myocyte hypertrophy, hyperplasia of nonmyocytic
      tissue components, increased contractility and heart rate, and increased
      ventricular volume. Although these changes serve to stabilize stroke volume and
      cardiac output following an insult to the myocardium, the chronic and continual
      activation of these systems produces ventricular dilatation and deleterious
      remodelling at a chamber level and progressive myocyte dysfunction at a cellular
      level. Because these systems are cross-regulated, inhibition of one of them
      attenuates the activity of the other. This appears to be especially true in the
      failing heart, where angiotensin converting enzyme inhibitors can produce
      substantial anti-adrenergic effects in individuals with high levels of adrenergic
      activation. The anti-adrenergic properties of angiotensin converting enzyme
      inhibitors may be at least partially responsible for the salutary effects of
      these agents in the clinical setting of heart failure or ischaemic heart disease.

PMID- 8869135
TI  - Role of angiotensin converting enzyme inhibitors in preventing left ventricular
      remodelling following myocardial infarction.
AB  - Progressive changes typically occur in left ventricular (LV) architecture
      following moderate- to large-sized myocardial infarction (MI). These changes
      include early expansion and thinning of the infarct zone and subsequent increase
      in myocardial mass within the non-infarcted zone, with LV dilatation and loss of
      the normal elliptical configuration of the LV cavity. These changes are
      accompanied by impaired myocyte function and advancing clinical expression of
      heart failure. Numerous animal and human studies have documented inhibition of LV
      remodeling post-MI by angiotensin converting enzyme (ACE) inhibitors. Although
      the ideal timing for initiating treatment remains uncertain, evidence exists that
      benefit persists long after the time of initial injury. Mechanisms for the
      effects of ACE inhibitors on LV remodelling may be dependent on changes in
      myocardial load, may be load independent, or both. These effects are likely to be
      mediated by reductions in circulating and local tissue concentrations of
      angiotensin II and in bradykinin degradation. Regardless of the exact mechanism
      or mechanisms by which ACE inhibitors exert their favourable influence on LV
      remodelling, it is likely that this effect is a key mediator of the documented
      clinical benefits afforded by treatment with this class of agents.

PMID- 8869136
TI  - Potential role of angiotensin converting enzyme inhibitors in treatment of
      atherosclerosis.
AB  - Recent clinical data from the SOLVD (Studies on Left Ventricular Dysfunction) and
      SAVE (Survival and Ventricular Enlargement) studies have shown a significant
      reduction in ischaemic events with ACE inhibition. When the results of the two
      SOLVD and the SAVE trials were combined, the overall risk reduction in myocardial
      infarction with long-term ACE inhibitor treatment was 23% (P < 0.001) and the
      overall risk reduction for hospitalizations for unstable angina 15%. The time
      frame of the clinical effects suggests that ACE inhibitors may be working through
      an antiatherosclerotic mechanism, and genetic, epidemiological and mechanistic
      data suggest that the renin-angiotensin-aldosterone system may play a role in the
      atherosclerotic process. Genetic and epidemiological evidence has shown that an
      activated renin-angiotensin aldosterone system is associated with a higher
      incidence of myocardial infarction, and mechanistic studies have demonstrated
      that ACE inhibition can produce antiatherosclerotic effects in animal models. The
      antiatherosclerotic effects of ACE inhibitors may be mediated at one of several
      steps in the atherosclerotic pathway: blocking plaque formation, plaque rupture,
      or thrombus formation.

PMID- 8869137
TI  - Behavioural and arousal-related influences on breathing in humans.
AB  - This review has described the many behavioural and arousal-related influences on
      breathing and the extent of these influences in humans. The chief examples have
      included the effect on breathing of altered mental activity, wakefulness and
      sleep, and learned respiratory responses. Determining the precise neurological
      mechanisms underlying these effects represents a difficult challenge to
      respiratory physiologists who seek to understand the respiratory control system
      of awake behaving humans. Nevertheless, insight into the various forebrain and
      brainstem inputs to respiratory muscles has been gained by studies of breathing
      during particular behaviours (when either voluntary or reflex breathing
      predominates) or in particular neurological patients (in whom either voluntary or
      reflex breathing is defective). With developments in brain imaging techniques,
      such as functional magnetic resonance imaging, it may soon be possible to
      determine more precisely the various anatomical sources and timing of the motor
      commands to breathe during different behaviours, states of arousal and sleep.

PMID- 8869138
TI  - Electrophysiological and ultrastructural events evoked by methacholine and
      intracellular photolysis of caged compounds in cultured ovine trachea submucosal
      gland cells.
AB  - Cultured ovine trachea submucosal gland cells release lysozyme in response to
      extracellular application of secretagogues, including the muscarinic receptor
      agonist methacholine (20 microM). Investigation of the ultrastructure has shown
      that these cells contain electron-dense cored granules, which differ from the
      intact tissue, but appear to be released in response to the application of
      methacholine and can be arrested during exocytosis by the application of tannic
      acid. The release process appears to be linked to electrophysiological events
      activated by methacholine. Extracellular application of methacholine and
      intracellular photorelease of Ca2+ from DM-nitrophen evoked similar events
      suggesting that a rise in intracellular Ca2+ may occur following muscarinic
      receptor activation. Measurements of the reversal potential and the inhibitory
      action of the chloride channel blocker niflumic acid (10 microM) indicated that
      Ca(2+)-activated Cl- channel activity underlies these events. Some of the
      cultured submucosal gland cells also responded similarly to intracellular
      photorelease of inositol 1,4,5-trisphosphate, suggesting a possible link between
      muscarinic receptor occupation by agonist, release of calcium from stores, and
      activation of Ca(2+)-activated Cl- current. Secretion of lysozyme, methacholine
      activated currents and currents evoked by intracellular photorelease of Ca2+ were
      also attenuated by the potent bronchodilator Ro 31-6930 (1 microM). We conclude
      that Ca(2+)-activated Cl- conductances play an important role in secretory
      processes in cultured submucosal gland cells. This may have a bearing on both
      physiological control of secretory events and regulation of the nature of airway
      surface liquid. Ca(2+)-activated Cl- channels may offer a potential target site
      for novel therapeutic agents.

PMID- 8869139
TI  - The action of knee joint afferents and the concomitant influence of cutaneous
      (sural) afferents on the discharge of triceps surae gamma-motoneurones in the
      cat.
AB  - Electrical stimulation of group II joint afferents of the posterior articular
      nerve (PAN) to the knee evoked short-latency facilitation and/or inhibition of
      the background discharge of gastrocnemius-soleus (GS) gamma-motoneurones in
      decerebrated spinal cats. The latencies of these responses were consistent with
      mediation via segmental oligosynaptic spinal pathways. In addition, a longer
      latency facilitation was frequently observed. Mechanical non-noxious stimulation
      of the skin within the field of innervation of the sural nerve, on the lateral
      aspect of the heel, suppressed the short-latency facilitation, but not the
      inhibition or long-latency facilitation. Brief mechanical indentation of the
      posterior aspect of the knee joint capsule could elicit facilitation or
      inhibition of gamma-motoneurones. Facilitation, but not inhibition, was blocked
      by anaesthesia or section of the PAN. Both actions could be suppressed by
      mechanical stimulation of the heel. We conclude that GS gamma-motoneurones
      receive both facilitatory and inhibitory segmental inputs from group II articular
      afferents arising in the knee joint. Cutaneous afferents from the sural field
      exert a selective inhibitory influence over the facilitation of fusimotor
      discharge by articular afferents.

PMID- 8869140
TI  - The role of adenosine receptors in the rostral ventrolateral medulla in the
      cardiovascular response to defence area stimulation in the rat.
AB  - The effects of microinjections of adenosine and an adenosine receptor antagonist
      into the rostral ventrolateral medulla (RVLM) on the cardiovascular changes
      associated with the defence reaction were investigated in anaesthetized rats.
      Responses to electrical and chemical stimulation in RVLM were determined in alpha
      chloralose-anaesthetized, paralysed and artificially ventilated rats.
      Microinjections of adenosine (10 nM) and the adenosine receptor antagonist 8
      sulphophenyl-theophylline (8-SPT; 0.12 microM) were made into the RVLM and their
      effects on arterial pressure (ABP), heart rate (HR) and skeletal muscle blood
      flow determined. Microinjections of adenosine into the RVLM evoked either an
      increase or a decrease in ABP, with variable effects on HR. These actions of
      adenosine were blocked by prior injection of 8-SPT at the same site. Histological
      analysis showed that adenosine evoked an increase in arterial pressure when
      injected into rostral areas of the RVLM, and a depressor response when injected
      into caudal regions. Furthermore, microinjections of adenosine into the RVLM
      augmented the increase in ABP evoked by electrical stimulation of the
      hypothalamic defence area (HDA). Whilst microinjection of 8-SPT into RVLM had no
      effect on the baseline levels of the variables measured, it reduced the HDA
      evoked increase in ABP. From these results we propose that adenosine modulates
      the cardiovascular changes evoked upon stimulation of the HDA via an action on
      sympatho-excitatory neurones within the rostral ventrolateral medulla.

PMID- 8869141
TI  - Transport of sodium across the isolated bovine rumen epithelium: interaction with
      short-chain fatty acids, chloride and bicarbonate.
AB  - Unidirectional transport rates of sodium (22Na+) and chloride (36Cl-) across
      bovine rumen epithelium were measured in vitro by the Ussing chamber technique.
      The active and short-chain fatty acid (SCFA)-stimulated sodium transport was
      shown to fit Michaelis-Menten kinetics, and was rate limited mainly by one
      transport system, characterized by a Km of 43 mmol l-1 Na+ and a Jmax (maximal
      transport rate) of 6.2 mumol cm-2 h-1 Na+. It was confirmed that the basolateral
      Na+,K(+)-ATPase was essential for active sodium transport, and that an apical
      amiloride-sensitive sodium transport system (Na(+)-H+ exchange) was involved in a
      minimum of 60-70% of the active sodium transport in the presence of SCFAs
      (butyrate). The main part of both the mucosal-serosal (MS) and serosal-mucosal
      (SM) sodium flux was sensitive to an applied electrical potential difference
      (PD). It is noteworthy that an applied PD, equal to the in vivo PD (+30 mV, lumen
      as reference), abolished net transport of sodium. The stimulating effect of a
      mixture of acetate, propionate and butyrate on active sodium transport was
      confirmed, and it was further shown that the stimulating effect of each of the
      three SCFAs was nearly equal. Analogues of naturally occurring SCFAs (isobutyrate
      and 2-ethyl-butyrate) did not stimulate active sodium transport, but inhibited
      the stimulating effect of butyrate. The stimulating effect of butyrate was
      clearly concentration dependent and showed a maximum at approximately 20 mmol l-1
      butyrate. Above this limit active sodium transport was decreased with increasing
      butyrate concentration. This suggests that there was a limit to the amount of
      butyrate that could be handled by the epithelium. The active sodium transport was
      clearly correlated with the chloride concentration, and was significantly
      reduced, but not abolished, by replacement of chloride with gluconate. Active
      transport of chloride was stimulated by butyrate and reduced by the Na(+)-H+
      exchange inhibitor amiloride (3 mmol l-1). There was no effect of the Cl(-)-HCO3-
      exchange inhibitor DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid; 0.5
      mmol l-1) on sodium transport. HCO3- (13 mmol l-1) and CO2 (5%) themselves had
      only a small and non-significant stimulating effect on sodium fluxes, however, in
      the presence, but not the absence of HCO3- and CO2 in the experimental solutions
      acetazolamide (1 mmol l-1) significantly reduced active sodium transport. It is
      concluded that SCFAs could stimulate the active sodium and chloride transport as
      a result of their metabolism. The CO2 produced could stimulate apical Na(+)-H+
      and Cl(-)-HCO3- exchangers running in parallel via increased H+ and HCO3-
      gradients.

PMID- 8869142
TI  - The effect of intraluminal flow rate on glomerulotubular balance in the proximal
      tubule of the rat kidney.
AB  - To differentiate intraluminal from peritubular factors in mediating the
      glomerulotubular balance, single nephron filtration rate (SNGFR) and reabsorption
      were measured by total collection from the last proximal segment before, and
      during, externally applied mechanical compression of an early proximal
      convolution of ninety-three rat nephrons. SNGFR fell from 55.6 +/- 2.3 nl min-1
      during control conditions to 34.5 +/- 2.0 nl min-1 during compression (P <
      0.0001) in sixty tubules ('responders'). Absolute reabsorption fell from 41.8 +/-
      2.0 to 28.4 +/- 1.8 nl min-1 (P < 0.0001), while percentage reabsorption rose
      from 75 +/- 2 to 82 +/- 2% (P < 0.0001). These effects were reversible and
      independent of whether the compression was applied before or after the control
      collection. In thirty-three proximal tubules the compression procedure was not
      successful ('non-responders'), SNGFR remaining unchanged (36.1 +/- 2.9 vs. 36.9
      +/- 2.9 nl min-1, P > 0.3). Absolute and percentage reabsorptions rose slightly,
      albeit significantly, from 26.1 +/- 2.1 to 30.7 +/- 2.4 nl min-1 (P < 0.0001) and
      from 75 +/- 3 to 85 +/- 2% (P < 0.0001). Thus, the response of reabsorption to
      changes in intraluminal flow is composed of two different adaptive mechanisms.
      The slowing of flow is present in both sets of tubules and causes a slight
      increase in resorption; the change in filtration per se is present only in the
      first set of responders, and causes an SNGFR-dependent consensual change in
      resorption.

PMID- 8869143
TI  - The role of circulating catecholamines in the depletion of parotid acinar
      granules in conscious rats in the cold.
AB  - The possibility that circulating catecholamines might affect parotid gland
      function during feeding (over a period of 80 min) and cold stress (2-4 degree C)
      was investigated in rats that had been fasted for 30 h. In the first set of
      experiments, in which the glands had been sympathectomized by removing both
      superior cervical ganglia 10-12 days previously, there was a substantial
      reduction in the density of acinar secretory granules (42% compared with non-fed
      animals in the cold) and in the total glandular amylase activity (54%). However,
      similar, or even greater, losses were recorded in rats subjected to additional
      bilateral adrenal medullectomy and pretreatment with atropine and alpha- and beta
      adrenoceptor blockers. The losses were therefore attributed to activation of
      parasympathetic non-adrenergic, non-cholinergic mechanisms. In a second set of
      experiments, employing only morphometric assessment, the parasympathetic
      auriculotemporal nerve was cut on one side in addition to bilateral sympathectomy
      and, as a further precaution, the animal was atropinized. It was then found that
      there was a loss of 17% of granules in the parasympathectomized plus
      sympathectomized gland, but not the contralateral gland, of non-fed cold-exposed
      rats compared with non-fed animals kept at room temperature. When rats were fed
      as well as exposed to cold the number of granules in parasympathectomized plus
      sympathectomized glands fell by 46% compared with similar non-fed animals in the
      cold and by 55% compared with those at room temperature. After adrenal
      medullectomy, cold exposure alone had no effect on the granular density of
      parasympathectomized plus sympathectomized glands but, when combined with
      feeding, granular loss amounted to 30%. Pretreatment with a combination of alpha-
      and beta-adrenoceptor blocking agents abolished this effect. Thus circulating
      catecholamines liberated not only from the adrenal medulla but also from other
      sources (extraglandular adrenergic nerve terminals and extra-adrenal chromaffin
      tissue) are able to induce losses in the number of acinar granules in the
      parasympathectomized plus sympathectomized glands. However, a high degree of
      sensitization of the parotid acinar cells may be required to allow the response
      to become manifest.

PMID- 8869144
TI  - Hepatic branch vagotomy enhances feeding in response to centrally elicited
      glucose deprivation in rats.
AB  - Intracerebroventricular (I.C.V.) administration of 2-deoxy-D-glucose (2-DG)
      produces glucose deprivation-induced ('glucoprivic') feeding and sympathoadrenal
      activation. To find out whether peripheral mechanisms modulate centrally elicited
      glucoprivic feeding the effect of hepatic branch vagotomy (HBV) compared with
      sham vagotomy (SV) on the feeding response to I.C.V.-injected 2-DG (1.2 or 2.4 mg
      per rat) was tested in rats fed a fat-enriched diet (18% fat). 2-DG was injected
      into the lateral ventricle 1 h after after dark onset, at light onset or 6 h
      after light onset of the 12 h light-12 h dark cycle. Apart from one (1.2 mg 2-DG
      injected 1 h after dark onset) out of six experiments, HBV enhanced glucoprivic
      feeding. This finding is consistent with the assumption that centrally elicited
      glucoprivic feeding is antagonized by peripheral stimuli signalled to the brain
      through the hepatic vagus branch.

PMID- 8869145
TI  - Responses of glucose metabolism to insulin in perfused mammary tissue of
      lactating rats: influence of dietary history and recent insulin experience.
AB  - Mammary tissue of lactating rats has been perfused in situ to measure the effects
      of insulin and of previous dietary history on utilization of glucose and its
      incorporation into lipid. This experimental model allows the direct effects of
      insulin on mammary tissue to be characterized without influence from the
      secondary consequences of insulin administration that may accompany treatment of
      the intact animal with this hormone. In mammary tissue from rats starved for 24
      h, glucose utilization was stimulated by insulin treatment. The threshold for
      insulin response was between 0.01 and 0.02 mU ml-1, and no further stimulation
      took place between 0.02 and 0.04 mU ml-1 insulin. The maximum response was
      reached within 50 min of the onset of insulin challenge and remained at a plateau
      value regardless of whether insulin was continuously present or was withdrawn
      after 15 min. Incorporation of glucose into lipid contributed to this glucose
      uptake. When no insulin was present in the perfusate, the rate of this process
      was around 3-fold greater in perfused mammary tissue from fed lactating rats than
      from those starved for 24 h. Insulin accelerated lipogenesis from glucose
      approximately 3- and 2-fold, respectively, in these two experimental groups. As
      for glucose uptake, the role of insulin in the regulation of mammary lipogenesis
      appeared to be to 'prime' the tissue and commit it to a response that was
      subsequently insulin independent.

PMID- 8869146
TI  - Continuous versus single drainage of milk from the bovine mammary gland during a
      24 hour period.
AB  - Five primiparous and five multiparous cows were used to determine if mammary
      cisternal storage of milk during a 24 h period of milk accumulation limited milk
      secretion. In addition, we investigated if there is a parity effect for the
      capacity of the mammary cisternal compartment to hold a 24 h accumulation of milk
      secretion, and studied the movement of milk from the alveolar compartment into
      the cisternal compartment. All cows were fitted with catheters in all teats in
      order to collect cisternal and alveolar milk fractions separately. For a 24 h
      period of milk accumulation, the milk was drained once (after 24 h) from one side
      of the udder (OD), and continuously from the other side of the udder (CD). There
      was no significant parity effect for cisternal, alveolar and total milk volumes
      at 24 h. Therefore, data from primi- and multiparous cows were pooled for
      subsequent analyses. Cisternal milk volume from CD glands was higher than that
      from OD glands (P < 0.01), indicating that cisternal storage of milk in the
      mammary gland may be limiting to milk secretion during 24 h milking intervals.
      Alveolar volumes did not differ between OD and CD, but, as a result of the higher
      cisternal milk volume, total milk volume was highest in the CD glands (P = 0.05).
      Movement of milk from the alveolar into the cisternal compartment was
      intermittent. Moreover, analyses of the slopes of individual milk accumulation
      profiles of the first 6 h of accumulation revealed that the cisternal compartment
      starts filling immediately following milking, although the rate of filling is
      relatively low until 7-8 h postmilking.

PMID- 8869147
TI  - Physiological regulation of gaba uptake by rat pyloric antral mucosa.
AB  - Endocrine cells of the pyloric antral mucosa are known to take up gamma-amino-n
      butyric acid (GABA), but the functional significance of this is uncertain. We now
      report that specific uptake of [3H]GABA by rat antral, but not corpus, mucosa is
      enhanced after fasting for 48 h. Decreased extracellular GABA in fasted rats
      could account for known changes in antral endocrine cell function.

PMID- 8869148
TI  - Repeated exposure to cationic immunoliposomes activates effective gene transfer
      to human glioma cells.
AB  - The use of whole immunoglobulin G (IgG) and F(ab')2 of the G-22 monoclonal
      antibody associated with cationic liposomes (immunoliposomes) and the effect of
      repeated exposure were investigated for the transfection of the LacZ gene to
      various glioma cell lines. Immunoliposomes associated with either whole IgG or
      F(ab')2 monoclonal antibody caused an about 2-fold increase in beta-galactosidase
      activity compared with liposomes associated with no antibody in glioma cell lines
      expressing the CD44 antigen. beta-Galactosidase activity was further increased by
      about 2-fold by repeated exposure compared with single exposure. A glioma cell
      line not expressing the CD44 antigen showed no such increase in beta
      galactosidase activity. These results indicate that repeated exposure of cationic
      immunoliposomes achieves a higher transfection efficiency and is a potentially
      effective method of gene therapy for patients with malignant glioma.

PMID- 8869149
TI  - Modulation of transforming growth factor-beta secretion from malignant glioma
      cells by interleukin-1 beta.
AB  - Malignant glioma cells secrete transforming growth factor-beta (TGF-beta) which
      has potent immunosuppressive properties. We investigated the effect of
      interleukin-1 beta (IL-1 beta) on TGF-beta secretion from malignant glioma cells
      in vitro. T98G glioblastoma cells were treated with various doses of IL-1 beta
      and the TGF-beta activity in the supernatant was determined using a specific
      bioassay. Six other human malignant glioma cell lines were also treated with 1000
      U/ml of IL-1 beta, and the TGF-beta activity in the supernatants was determined.
      The effect of IL-1 beta on the growth of tumor cells was also assessed by a
      bioassay using crystal violet which reflects the actual cell number in the plate
      wells. IL-1 beta treatment resulted in inhibition of TGF-beta secretion in two
      malignant glioma cell lines. TGF-beta secretion from T98G cells was suppressed by
      IL-1 beta in a dose-related manner. However, IL-1 beta treatment resulted in an
      obvious increase (> 20%) of TGF-beta secretion in two tumor lines, and a slight
      increase (< 20%) in three tumor lines. IL-1 beta did not affect the growth of
      four malignant glioma cell lines, and only slightly affected the growth of the
      other three cell lines. IL-1 beta modulates TGF-beta secretion from malignant
      glioma cells, but not in a consistent way.

PMID- 8869150
TI  - Protective effect of nilvadipine on focal cerebral ischemia in spontaneously
      hypertensive rats.
AB  - The protective effect of nilvadipine, a Ca2+ antagonist, on cerebral ischemia was
      investigated in spontaneously hypertensive rats. The 12-week-old animals were
      treated for 7 days with either nilvadipine or vehicle using osmotic pumps
      implanted subcutaneously. Group 1 animals (n = 10) received the vehicle, and
      Group 2 (n = 10) and 3 animals (n = 10) received 1 and 3 mg/kg/day nilvadipine,
      respectively. The left middle cerebral artery was occluded under halothane
      anesthesia on the 6th day of treatment, and neuropathological outcomes were
      quantified 24 hours later. The systolic blood pressure measured before occlusion
      decreased to 137 +/- 9 mmHg (Group 2) and 130 +/- 9 mmHg (Group 3), compared to
      189 +/- 12 mmHg for Group 1 (p < 0.05). The percentage infarct volumes in Groups
      1-3 were 39 +/- 3%, 37 +/- 2%, and 34 +/- 3%, respectively (p < 0.05, Groups 1
      vs. 3). Therefore, nilvadipine decreased the infarct size dose-dependently.
      Nilvadipine has a protective effect against cerebral ischemia in rats with
      chronic hypertension. Neuropathological findings suggest that nilvadipine may act
      at the ischemic penumbra. Nilvadipine may have the additional benefit of reducing
      the consequences of a possible later stroke in patients with hypertension (one of
      the risk factors for stroke).

PMID- 8869151
TI  - Vascular response to hyperoxemia in rat brain surface microvessels.
AB  - The effects of hyperoxemia on pial vessel diameters were studied in rats using a
      cranial window technique. The brain surface was superfused with mock
      cerebrospinal fluid at 5 ml/hr, and the intracranial pressure was maintained at 5
      mmHg. Animals were artificially ventilated, and the arterial carbon dioxide
      tension was constantly controlled in each animal. Arterioles (14-90 microns
      diameter during air inhalation) constricted significantly according to the
      arterial oxygen tension (PaO2) increase: 94 +/- 7% (30% O2), 91 +/- 8% (60% O2),
      and 88 +/- 8% (100% O2). The percentage diameter change per mmHg PaO2 increase
      was 0.1% under normoxemia, but became less under hyperoxemia (0.025% and 0.01%
      per mmHg during 30%-to-60% and 60%-to-100% O2 inhalations, respectively). The
      diameter change between 60% and 100% O2 inhalations was not significant. There
      was no significant relationship between the vascular response and the control
      diameter. Some small arterioles (< or = 50 microns diameter) underwent marked
      constriction (-20% to -35%), but there were no large vessels (> 50 microns
      diameter) showed a constriction greater than -20%. Venules (17-114 microns
      diameter) did not have a significant response to hyperoxemia. The
      vasoconstriction of pial arterioles was proportional to arterial O2, but the
      relationship was not linear.

PMID- 8869152
TI  - Non-traumatic arteriovenous fistulas of the scalp treated by a combination of
      embolization and surgical removal.
AB  - Three patients with non-traumatic arteriovenous fistulas (AVFs) of the scalp were
      treated by embolization using acrylate glue through the transarterial route or by
      direct puncture of the lesions and then surgical resection. Complete cure was
      achieved in all three patients. Selective angiography is indispensable in the
      correct diagnosis of scalp AVFs. Embolization facilitates surgical removal when
      necessary, and this combination is the treatment of choice for scalp AVFs.

PMID- 8869153
TI  - Magnetic resonance imaging of brain death.
AB  - Fifteen patients with clinical diagnosis of brain death were examined by magnetic
      resonance (MR) imaging. Aortography with intraarterial digital subtraction
      angiography (IADSA) was also performed in nine patients. MR imaging indications
      of the flow void phenomenon were evaluated in the cavernous portion of internal
      carotid artery (ICA) and the middle or anterior cerebral artery, and compared
      with the IADSA findings. The relative intensities of gray and white matters were
      also measured. MR imaging showed that flow voids were absent in the ICA in all
      eight patients in whom non-filling was confirmed by IADSA. In one patient, IADSA
      demonstrated intracranial flow despite the diagnosis of brain death and the flow
      void pattern was normal. Serial MR imaging showed disappearance or abnormality of
      flow voids after brain death in six patients and absence before brain death in
      one. Spotty flow voids became visible in the unilateral ICA of one case after
      brain death. Partial residual flow voids may be caused by to-and-fro blood
      movement which was demonstrated by transcranial Doppler sonography. The normal
      flow void pattern was seen in none of these patients, therefore absence of flow
      voids indicates cessation of intracranial blood flow. Proton density and T2
      weighted MR images showed dissociated intensity changes between white and gray
      matters, which were thought to be characteristic of brain death. In conclusion,
      MR imaging can achieve non-invasive diagnosis of the non-filling phenomenon in
      patients with brain death.

PMID- 8869154
TI  - Solitary metastasis of lung cancer to the cerebellopontine angle--case report.
AB  - A 44-year-old male presented with a solitary cerebellopontine angle (CPA)
      metastasis from lung cancer. His initial symptoms were vertigo and hearing loss
      beginning 5 months after the diagnosis of the primary cancer. Two months later,
      right facial paresis developed. His neurological deterioration was rapid.
      Magnetic resonance (MR) imaging with enhancement disclosed the CPA tumor. The
      tumor was partially removed through the retroauricular retromastoid approach.
      Histological examination of the specimen revealed adenocarcinoma. The
      characteristic rapidly progressive symptoms and MR imaging with enhancement are
      the most sensitive and essential examinations for this lesion.

PMID- 8869155
TI  - Posterior fusion for odontoid fracture in an infant--case report.
AB  - A 2-year-3-month-old girl presented with a rare displaced odontoid fracture. She
      was managed nonoperatively by manipulation followed by 3-month extracorporeal
      fixation with a halo brace. However, lateral radiography revealed recurrent
      dislocation at the base of the odontoid process. Magnetic resonance imaging
      demonstrated a "synchondrotic slip." She therefore underwent posterior wiring
      with iliac bone grafting to prevent pseudoarthrosis. The odontoid process had
      fused to the axis at 4 months postoperatively. Surgical management should be
      considered as a treatment method for pediatric odontoid fracture because of the
      difficulties in maintaining long-term immobilization and confirming the union.

PMID- 8869156
TI  - Intraoperative radiation therapy and chemotherapy for huge choroid plexus
      carcinoma in an infant--case report.
AB  - A 2-month-old boy presented with a huge choroid plexus carcinoma in the left
      cerebral hemisphere. Almost total resection of the tumor was achieved, but a
      remnant abruptly enlarged 5 months later, requiring reoperation. After radical
      resection of the tumor, intraoperative radiation (10 Gy) was delivered.
      Postoperative chemotherapy was performed with methotrexate and vincristine,
      selected on the basis of in vitro chemosensitivity testing. No recurrence of the
      tumor was detected 18 months after the second operation. Radical surgery with
      these adjuvant therapies may be a good method to control this aggressive disease
      in infants.

PMID- 8869157
TI  - Low grade astrocytoma in the medial part of the frontal lobe manifesting as
      paroxysmal speech disturbance--case report.
AB  - A right-handed 48-year-old female had clustered groups of seizures characterized
      by speech disturbance (attacks of verbal repetition and speech arrest) over a
      period of 7 years. Later, speech arrest was accompanied by perioral focal
      seizures. Magnetic resonance imaging and surgery found a low grade astrocytoma,
      centered in the left supplementary motor area. Postoperatively, no seizures or
      speech disturbances occurred for 3 years. This case confirms the main function of
      the supplementary motor area of the dominant hemisphere is connected with the
      initiation of speech and the setting into motion of the mechanism of speech.

PMID- 8869158
TI  - Sensitivity of rat frontal cortical neurones to nicotine is increased by chronic
      administration of nicotine and by lesions of the nucleus basalis magnocellularis:
      comparison with numbers of [3H]nicotine binding sites.
AB  - The effects of chronic nicotine treatment and of unilateral AMPA lesion of the
      nucleus basalis magnocellularis (nbm) on the sensitivity of frontal cortical
      neurones to iontophoretically applied nicotine were studied. Chronic nicotine
      treatment increased the number of [3H]nicotine binding sites from 2.9 to 3.9 pmol
      g-1 wet weight, and increased the proportion of cortical neurones responding to
      nicotine from 32.3% to 60.0%. After unilateral nbm lesions, the densities of AChE
      positive fibers and [3H]nicotine binding sites were reduced by approximately 97%
      and 55%, respectively, and the proportion of neurones responding to nicotine
      increased from 32.3% to 53.8%. The two treatments, chronic nicotine
      administration and nbm lesion, also increased the size of individual neuronal
      responses, prolonged their duration, and shortened the response latency.
      Responses to glutamate were unaffected by either procedures. The results show
      that the increase in [3H]nicotine binding produced by chronic nicotine
      administration is associated with an increased response to iontophoretically
      applied nicotine, suggesting that the receptor upregulation induced by the
      chronic treatment were functional. Less easily explained is the association
      between increased sensitivity of frontal cortical neurons to nicotine after nbm
      lesion with a decreased receptor density. It is suggested that a substantial
      proportion of nicotinic receptors are located presynaptically, and that their
      loss after lesion concealed an upregulation at postsynaptic sites.

PMID- 8869159
TI  - Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine
      system.
AB  - In previous studies, we have demonstrated that chronic administration of morphine
      or cocaine produces some common biochemical adaptations in the ventral tegmental
      area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine
      system implicated in the reinforcing actions of these and other drugs of abuse.
      Since this neural pathway is also implicated in the reinforcing actions of
      ethanol, it was of interest to determine whether chronic ethanol exposure results
      in similar biochemical adaptations. Indeed, as seen for chronic morphine and
      cocaine treatments, we show here that chronic ethanol treatment increased levels
      of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and
      decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like
      morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein
      kinase activity in the NAc. These actions of ethanol required long-term exposure
      to the drug, and were in most cases not seen in the substantia nigra or
      caudateputamen, components of the nigrostriatal dopamine system studied for
      comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells
      frequently reflect altered states of activation of the cells. Moreover,
      increasing evidence indicates that ethanol produces many of its acute effects on
      the brain by regulating NMDA glutamate and GABAA receptors. We therefore examined
      the influence of chronic ethanol treatment on levels of expression of specific
      glutamate and GABA receptor subunits in the VTA. It was found that long-term, but
      not short-term, ethanol exposure increased levels of immunoreactivity of the
      NMDAR1 subunit, an obligatory component of NMDA glutamate receptors, and of the
      GluR1 subunit, a component of many AMPA glutamate receptors; but at the same
      time, long-term ethanol exposure decreased immunoreactivity levels of the alpha 1
      subunit of the GABAA receptor complex. These changes are consistent with an
      increased state of activation of VTA neurons inferred from the observed increase
      in tyrosine hydroxylase (TH) expression. These results demonstrate that chronic
      ethanol exposure results in several biochemical adaptations in the mesolimbic
      dopamine system, which may underlie prominent changes in the structural and
      functional properties of this neural pathway related to alcohol abuse and
      alcoholism.

PMID- 8869160
TI  - Interhemispheric modulation of dopamine receptor interactions in unilateral 6
      OHDA rodent model.
AB  - A critical assumption in the unilateral 6-hydroxydopamine (6-OHDA) model is that
      interactions between the intact and denervated hemispheres do not influence the
      response to insult. The present study examined this issue by assessing the
      effects of unilateral substantia nigra 6-OHDA lesions in rats that previously had
      received corpus callosum transections, a treatment designed to minimize
      interhemispheric influences. Quantitative autoradiography in the caudate-putamen
      ipsilateral to the lesion revealed that corpus callosum transection did not alter
      the increase in D2-like receptors ([125I]-epidepride-labeled sites) that is
      induced by unilateral 6-OHDA lesion. There were no effects of either 6-OHDA
      lesion or transection on D1 receptor density ([125I]-SCH23982 autoradiography).
      As a functional endpoint, dopamine-stimulated cAMP efflux was measured in
      superfused striatal slices. In this paradigm, the net effect of dopamine (DA)
      represents a combination of D1 receptor-mediated stimulation and D2 receptor
      mediated inhibition. 6-OHDA lesion increased cAMP efflux induced by exposure to
      100 microM DA alone; corpus callosum transection did not alter this effect. An
      interaction between 6-OHDA lesion and transection status was revealed, however,
      by comparison of results obtained with DA alone vs. DA plus the D2 antagonist
      sulpiride (to block the D2 inhibitory effects of 100 microM DA). This comparison
      revealed two important effects of 6-OHDA lesion in rats with an intact corpus
      callosum: 1) a moderate decrease in dopamine D1 receptor-mediated stimulation;
      and 2) a dramatic decrease in the ability of D2 receptors to inhibit this
      stimulation. Corpus callosum transection prevented these effects of 6-OHDA. These
      results provide a biochemical demonstration of D1:D2 receptor uncoupling in
      unilateral 6-OHDA lesioned rats, and suggest that interhemispheric influences
      (e.g., contralateral cortico-striatal glutamatergic projections) may contribute
      to lesion-induced alterations in D1:D2 receptor interactions.

PMID- 8869161
TI  - Biochemical adaptations in the mesolimbic dopamine system in response to heroin
      self-administration.
AB  - Previous studies have shown that chronic, forced exposure to opiates produces
      specific biochemical adaptations in the ventral tegmental area (VTA) and nucleus
      accumbens (NAc). The functional consequences of these adaptations have been
      hypothesized to contribute to certain motivational aspects of drug addiction. In
      this study, the possibility that similar adaptations could occur in response to
      intermittent heroin self-administration was tested by comparing homogenates of
      VTA and NAc from rats self-administering heroin, rats receiving yoked injections
      of heroin, and rats receiving yoked injections of saline (controls). Tyrosine
      hydroxylase (TH) immunoreactivity was increased (31-38%) in the VTA and decreased
      (11%) in the NAc of heroin-exposed rats relative to controls. Heroin exposure
      also increased cAMP-dependent protein kinase (PKA) activity in both particulate
      (19-27%) and soluble (17-20%) fractions of the NAc, and decreased (16-17%) the
      level of Gi alpha immunoreactivity in this brain region. In contrast, no
      significant biochemical changes were found in the substantia nigra or caudate
      putamen, indicating a selective effect on the mesolimbic dopamine system.
      Overall, adaptations in the VTA and NAc of heroin-exposed rats were similar to,
      but generally smaller in magnitude than, adaptations produced by chronic morphine
      administration. However, in contrast to morphine-treated animals, heroin-exposed
      animals failed to display overt signs of opiate physical dependence, suggesting
      that adaptations in motivational systems may occur more readily than adaptations
      in brain regions associated with physical dependence.

PMID- 8869162
TI  - Stimulation of cortical acetylcholine efflux by FG 7142 measured with repeated
      microdialysis sampling.
AB  - The effects of the benzodiazepine receptor partial inverse agonist beta-carboline
      FG 7142 on cortical ACh efflux were determined using in vivo microdialysis in
      freely-moving rats. Additionally, a within-subjects, repeated-dialysis
      experimental design (four microdialysis sessions; removable dialysis probe) was
      evaluated as a method for measuring changes in basal and FG 7142-stimulated ACh
      efflux in the frontoparietal cortex. FG 7142 (4.0, 8.0, and 16.0 mg/kg) produced
      a 150-470% increase in cortical ACh efflux, with a dose-dependent effect on the
      duration of the increase in efflux. Basal cortical ACh efflux was lower in
      session 4 than in session 1. However, the ability of FG 7142 to stimulate efflux
      was unchanged by repeated dialysis testing. The ability of tetrodotoxin (1.0
      microM) to suppress both basal and FG 7142-stimulated ACh efflux was also
      unaffected by repeated dialysis testing. These results demonstrate that
      systemically administered benzodiazepine receptor inverse agonists stimulate
      cortical ACh efflux, and that repeated-measures experimental designs can be valid
      for determining certain changes in cortical ACh efflux with in vivo
      microdialysis.

PMID- 8869163
TI  - Prenatal cocaine exposure adversely affects development of the primate cerebral
      cortex.
AB  - This study was conducted to determine whether prenatal exposure to cocaine
      interferes with the development of the primate cerebral cortex. For this purpose,
      pregnant rhesus monkeys received cocaine orally (20 mg/kg/day in fruit or candy
      treats), twice a day from the 40th-102nd days of pregnancy (E40-E102), which is a
      period of corticogenesis in this species. The control group of pregnant animals
      received fruit or candy treats only. On E64 and E65, all animals received
      intravenous injections of [3H]thymidine. Monkeys were allowed to deliver at term.
      The offspring were sacrificed at age 2 months, and their brains were processed
      for histology and autoradiography. The analysis of cresyl violet-stained sections
      showed that prenatal treatment with cocaine significantly altered lamination of
      the primate cerebral cortex, in some cases completely blending distinction
      between individual layers. In addition, autoradiographic analysis revealed that
      in the control animals, [3H]thymidine labeling concentrated in cortical layers V
      and/or IV depending on the cytoarchitectonic area observed. In contrast, drug
      treated animals displayed labeled cells in the white matter and cortical layer VI
      in addition to layers V and IV, suggesting inability of cortical cells to reach
      proper cortical layers. The number of labeled cells was also much lower in these
      animals. Finally, immunocytochemical studies with antisera directed toward glial
      fibrillary acidic protein showed that prenatal exposure to cocaine had dramatic
      effect on the glial fibers normally observed in the upper cortical layers. In
      many cortical regions of cocaine-treated animals, we observed practically no such
      fibers. This study demonstrates that cocaine administered during pregnancy can
      significantly affect the development of the primate cerebral cortex.

PMID- 8869164
TI  - N-methyl-D-aspartate acutely increases proenkephalin mRNA in the rat striatum.
AB  - Studies in which glutamate (GLU) neurotransmission has been reduced at striatal
      synapses have shown that GLU influences the biosynthesis of certain peptide
      cotransmitters by striatal neurons. The present experiment was designed to test
      the effects of direct activation of the NMDA or AMPA types of GLU receptor on the
      levels of two mRNAs that encode the peptide cotransmitters met5-enkephalin (ME)
      and substance P (SP). In situ hybridization histochemistry of forebrain tissue
      sections from rats 8 h after a single intracerebroventricular infusion of NMDA or
      AMPA revealed a significant and dose-dependent elevation (to a maximum of almost
      50%) of striatal ME mRNA when compared to vehicle-injected controls. SP mRNA was
      not significantly affected. NMDA was more effective than AMPA over the dose range
      used. Pretreatment with a potent and highly specific AMPA antagonist (NBQX)
      predictably blocked the AMPA-mediated elevation, and was only slightly effective
      against the NMDA-induced response. In striking contrast, pretreatment with a
      potent and highly selective NMDA antagonist (CGP37849) fully opposed both the
      NMDA- and the AMPA-mediated elevation of ME mRNA. These data further implicate
      the NMDA receptor in the regulation of peptide cotransmitter gene transcription.
      They suggest also that the AMPA receptor may play an indirect, synergistic role
      in the genetic responses of striatal neurons to GLU transmission.

PMID- 8869165
TI  - Effects of electrical stimulation of the central nucleus of the amygdala on the
      in vivo electrophysiological activity of rat nigral dopaminergic neurons.
AB  - The central nucleus of the amygdala (CeA) receives a dopaminergic (DA)
      innervation from the midbrain. Among its many efferent projections, the CeA
      innervates the substantia nigra. The possibility that the CeA influences the
      activity of nigral DA neurons was evaluated. The effects of electrical
      stimulation of the CeA on the firing rate and pattern of nigral DA neurons were
      investigated in anesthetized rats. Poststimulus time histograms revealed that
      nigral DA cells were either inhibited (N = 15), excited (N = 13), or unresponsive
      (N = 17) to CeA stimulation (250 stimuli at 0.5 Hz). The mean (+/- SEM) latency
      to inhibition (24 +/- 9 msec) was significantly shorter than that for excitation
      (65 +/- 10 msec); the duration of inhibition (200 +/- 29 msec) was also
      significantly greater than the duration of excitation (86 +/- 11 msec) (P < 0.01
      for both). DA cells that were excited had basal firing rates significantly lower
      than those of the inhibited or unresponsive cells (P < 0.05). Preliminary data
      suggest that DA cell burst-firing increases or decreases, respectively, in
      association with stimulation-evoked increases or decreases in firing rate. The
      relatively long latencies for stimulation-evoked responses suggest that CeA
      projection neurons indirectly affect nigral DA neurons via polysynaptic pathways.
      These results demonstrate that the CeA has the ability to influence the activity
      of nigral DA neurons, consistent with the putative role of the CeA as an
      interface between the limbic and extrapyramidal systems. Given the crucial role
      of the amygdala in anxiety states, these findings suggest that DA cell function
      may also be affected in such disorders.

PMID- 8869166
TI  - Participation of presynaptic noradrenergic fibers in the suppression of alpha 2
      adrenoceptor activity by substance P at the nucleus reticularis gigantocellularis
      of the rat.
AB  - We applied reverse microdialysis and high performance liquid chromatography
      (HPLC) analysis to evaluate the participation of presynaptic noradrenergic
      neurotransmission in the suppression by substance P (SP) of alpha 2-adrenoceptor
      activity at the nucleus reticularis gigantocellularis (NRGC) in Sprague-Dawley
      rats anesthetized with pentobarbital sodium. Microinfusion of SP (600 microM/min)
      into the NRGC through a stereotaxically positioned microdialysis probe attenuated
      the hypotensive and bradycardiac actions of the alpha 2-adrenoceptor agonist,
      guanabenz (100 micrograms/kg, i.v.). This inhibitory effect correlated positively
      with the time course of elevation in the estimated extracellular concentrations
      of SP and norepinephrine (NE) in the NRGC. Direct microinfusion of NE (50 nM/min)
      into the NRGC also lessened the cardiosuppressant effects of guanabenz. These
      circulatory and NE responses to SP were, however, significantly blunted in rats
      in which the noradrenergic innervation in the NRGC was depleted with N-(2
      chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) pretreatment.
      Microinfusion of NE into the NRGC of DSP4-pretreated animals restored the
      attenuation of guanabenz-induced cardiovascular suppression. These results
      suggest that SP may depress the activity of alpha 2-adrenoceptor at the NRGC that
      are involved in circulatory regulation by increasing the extracellular
      concentration of NE via a presynaptic modulation of noradrenergic
      neurotransmission.

PMID- 8869167
TI  - Mapping dopamine transporters in the human brain with novel selective cocaine
      analog [125I]RTI-121.
AB  - The novel cocaine analog RTI-121 [3 beta-(4-iodophenyl)tropane-2 beta-carboxylic
      acid isopropyl ester] was evaluated as a probe for the in vitro labeling and
      localization of the dopamine transporter in the human brain. Saturation binding
      experiments conducted in sucrose-phosphate buffer (10 mM sodium phosphate, pH
      7.4, 0.32 M sucrose) revealed high- and low-affinity binding components with
      affinity values (KD) of 0.25 +/- 0.04 and 4.9 +/- 1.6 nM (mean +/- SE) and
      densities (Bmax) of 56.8 +/- 13.8 and 147.7 +/- 23.4 pmol/g tissue, respectively.
      In contrast, when saturation binding experiments were performed in phosphate
      buffered saline (10 mM Na2HPO4, 1.8 mM KH2PO4, 136 mM NaCl, 2.8 mM KCl, 10 mM
      NaI, pH 7.4), a 9-fold decrease in the density of the low-affinity component was
      noted, suggesting that the low-affinity RTI-121 binding site is associated with
      the region of the transporter involved in the ionic dependence of substrate
      recognition and/or uptake. The rank order of potency for inhibition of [125I]RTI
      121 binding to human caudate membranes demonstrates that the radioligand
      selectively labels the dopamine transporter (GBR 12909 > RTI-121 > mazindol >
      nomifensine > (-) cocaine > desipramine > citalopram). Autoradiographic mapping
      of [125I]RTI-121 revealed very high densities of cocaine recognition sites over
      areas known to be rich in dopaminergic innervation, including the caudate,
      putamen, and nucleus accumbens. Moderate densities were also observed over the
      substantia nigra and the ventral tegmental area. Low-to-background labeling of
      [125]RTI-121 was seen throughout the cerebral cortex, amygdaloid nuclei, globus
      pallidus, and thalamus. In comparison with the autoradiographic distribution of
      the cocaine analogs [3H]WIN 35,428 (or CFT) and [125I]RTI-55 (or beta-CIT), the
      labeling pattern for [125I]RTI-121 was more restricted. These studies demonstrate
      that [125I]RTI-121 labels dopamine-rich brain regions with greater selectivity
      than other currently available cocaine analogs, which makes it a potentially
      superior imaging probe for mapping the dopamine transporter in the human brain.

PMID- 8869168
TI  - Multiple brain abscesses following esophageal dilation.

PMID- 8869169
TI  - Blink reflex in meningomyelocele, with special reference to its usefulness in the
      evaluation of brainstem dysfunction.
AB  - The electrically elicited blink reflex (BR) was studied in 30 patients with
      meningomyelocele (MMC), including 21 with Chiari type II malformation. The
      relationship between the BR and brainstem auditory evoked potentials (BAEPs) is
      discussed with regard to its usefulness in the evaluation of MMC's brainstem
      dysfunction. The following results were obtained: (1) The R2 component was
      abnormal in 90% of these patients. The BR disclosed subclinical lesions in the
      medulla oblongata which were not detected by BAEPs alone. (2) In all patients in
      whom the BAEPs suggested the presence of stretched cochlear nerves, the BR
      indicated the existence of some dysfunction of the medulla oblongata. (3) No
      close relationship was found between the dysfunction detected by the BR and the
      degree of hindbrain anomaly on the neuroimaging. (4) Combining results from
      assessment of the measurement of the BR and BAEPs permits evaluation of the
      function of the fifth, seventh, and eighth cranial nerves, as well as the
      brainstem including the medulla oblongata, which is more comprehensive than
      evaluation by neuroimaging alone.

PMID- 8869170
TI  - Somatosensory evoked potentials to median nerve stimulation in meningomyelocele:
      what is occurring in the hindbrain and its connections during growth?
AB  - Twenty patients with meningomyelocele (MMC) and shunted hydrocephalus, ranging in
      age from 3 to 23 years old, underwent serial recording of short-latency
      somatosensory evoked potentials (SEPs) to median nerve stimulation, on the basis
      of which to assess the evolution of dysfunction in the brainstem and its
      connections (cervical spinal cord, cervical nerve roots, lower cranial nerves).
      Eighteen patients had Chiari type II malformations, none of which was
      symptomatic. In all 20 patients, serial SEP recordings were obtained repeatedly
      after periods ranging from 2 to 7 years. The results were as follows: (1) the
      ratio of EP-N13 interpeak latencies (IPLs) to body height (BH) tended to lengthen
      gradually after starting in the normal range with growth. (2) In contrast, the
      ratio N13-N20 IPLs/BH decreased continuously to the normal range with growth,
      after initial prolongation. These findings and our earlier studies of brainstem
      auditory evoked potentials suggest that compression and traction result in
      strangulation of the cervical spinal cord and kinked medulla as well as
      stretching of the cervical nerve roots and lower cranial nerves. However, primary
      intrinsic functional disorders of the brainstem appeared to improve gradually
      during growth. The natural history of Chiari type II malformations involves these
      opposing dynamic phenomena in the hindbrain and its connections.

PMID- 8869171
TI  - Neurodevelopmental outcome of hydrocephalus following intra-/periventricular
      hemorrhage in preterm infants: short- and long-term results.
AB  - Over a 5-year period (1984-1988) intra- and periventricular hemorrhage (IVH/PVH)
      was observed in 299 preterm infants. Sixty-eight infants developed
      posthemorrhagic hydrocephalus (PH); of these, 23 infants died and 40 infants
      could be followed up for assessment of neurological development (5 patients were
      lost to follow-up). At 1 year of corrected age 15% (25% at 5 year follow-up) of
      the infants were determined to have developed normally, 35% (25% at 5-year follow
      up) showed mild neurological symptoms and/or slight developmental delay, 32.5%
      (28% at 5-year follow-up) had handicaps and/or moderate mental retardation, and
      17.5% (22% at 5-year follow-up) had severe handicaps and/or severe mental
      retardation. There was a significantly worse outcome in infants with grade 4
      IVH/PVH (P < 0.05) and a significantly worse outcome in the group requiring
      ventriculoperitoneal (VP) shunt (P < 0.05). The results at 1 year of corrected
      age proved to be a quite realistic predictor of neurological functioning at 5
      years of age (80% predicted correctly in the non-shunted-group--one patient lost
      to follow-up; 95% predicted correctly in the shunted group--four patients lost to
      follow-up). Cystic periventricular leukomalacia had been diagnosed in 7 (10%)
      patients and was associated with poor neurodevelopmental outcome. Gestational
      age, birth weight, time of shunt placement, and peripartum asphyxia had no
      significant influence on neurodevelopmental outcome. Infants with shunt
      infections and a high number of shunt revisions were found to have a
      significantly worse neurodevelopmental outcome (P < 0.01).

PMID- 8869172
TI  - Use of a ventriculosubgaleal shunt in the management of hydrocephalus in children
      with posterior fossa tumors.
AB  - We present our experience with the use of ventriculosubgaleal shunting (VSGS) for
      the management of hydrocephalus associated with posterior fossa tumors in a
      consecutive series of 63 children. In 42 children, a temporary VSGS was inserted.
      There were no complications associated with the procedure, and it gave a period
      of several days in which to improve the general condition of the child, and to
      perform the necessary imaging studies, without an encumbering external drainage
      device. In most cases the VSGS could be removed after the posterior fossa
      surgery, without new general anesthesia. Other advantages and drawbacks of this
      technique are discussed.

PMID- 8869173
TI  - Anterior fontanelle pressure monitoring for the evaluation of asymptomatic
      infants with increased head growth rate.
AB  - We studied non-invasive intracranial pressure monitoring in 20 asymptomatic
      infants with increased head growth rate. Both basal anterior fontanelle pressure
      (AFP) traces and occurrence of pressure waves were analysed and compared with
      normal range values previously established. Eight recordings were classified as
      pathological; cerebral imaging showed subdural collections or ventricular
      dilatation in all cases. Five out of these eight infants further developed
      neurological deficits and/or increase of the ventricular size, and required
      neurosurgical procedures. Twelve infants had normal AFP traces; six of these had
      normal cerebral imaging and six showed enlargement of subarachnoid spaces with
      normal ventricles. All of these 12 patients normalised their head growth rate and
      remained asymptomatic. This observation suggests that AFP monitoring may be
      helpful in asymptomatic infants with increased head growth rate to identify a
      progressive intracranial process and the potential need for a neurosurgical
      procedure.

PMID- 8869174
TI  - Glial heterotopias of the nose: a report of two cases.
AB  - Two neonates are presented who had glial heterotopias of the nose, one with and
      the other without intracranial connections. It is important to distinguish these
      malformations from nasofrontal encephaloceles in order to avoid inadvertent
      exposure of the brain during surgical removal of the mass lesions. The
      distinction between them may not be clear clinically because of their similar
      pathogenesis.

PMID- 8869175
TI  - Cervico-thoracic neurenteric cyst: clinicoradiological correlation with
      embryogenesis.
AB  - Two cases of cervico-dorsal neurenteric cysts are presented, one located dorsal
      and the other ventral to the spinal cord, with associated Klippel-Feil anomaly,
      meningocele, spinal dysraphism and possibly spinal cord malformation. One patient
      was operated on as a neonate for a cervico-thoracic meningocele and presented
      during adolescence with spastic quadriparesis. Imaging revealed spina bifida, a
      dorsally located neurenteric cyst and a tendency towards split cord malformation.
      The other child presented with cervico-thoracic kyphoscoliosis and paraparesis.
      Imaging demonstrated persistence of a cervico-thoracic remnant of the primitive
      neurenteric canal through the upper thoracic spine.

PMID- 8869176
TI  - Plasma cell granulomas of the brain: pediatric case presentation and review of
      the literature.
AB  - Plasma cell granulomas (inflammatory pseudotumors) are benign inflammatory masses
      that have been observed in virtually every organ system but are most often
      described in the lung. Rare cases have been reported in which the brain and
      spinal cord are affected. We present the case of a 5-year-old girl with
      personality and behavioral changes, discovered to be harboring an intracerebral
      plasma cell granuloma. The literature on plasma cell granuloma of the central
      nervous system is discussed with emphasis on the clinical, radiological, and
      pathological features of these lesions.

PMID- 8869177
TI  - The United Kingdom cystic fibrosis epidemiology study.

PMID- 8869178
TI  - Update on the United States epidemiology study.

PMID- 8869179
TI  - Fibrosing colonopathy in children with cystic fibrosis.

PMID- 8869180
TI  - Direct assessment of gastrointestinal inflammation and mucosal immunity in
      children with cystic fibrosis.
AB  - Fibrosing colonopathy is a recently described complication of cystic fibrosis, of
      unknown aetiology but possibly related to treatment with high-dose pancreatic
      enzyme supplements. We have used a whole gut perfusion technique to study
      subclinical gut inflammation in cystic fibrosis patients; concentrations of
      haemoglobin, IgG, albumin, alpha-1-antitrypsin, granulocyte elastase, IL1 beta,
      and IL8 were measured in whole gut lavage fluid: 23 tests were performed in 17
      children with cystic fibrosis (20 elective tests, three lavages to treat distal
      intestinal obstruction syndrome (DIOS)). None has had fibrosing or haemorrhagic
      colitis. There were 12 tests in control children with constipation or
      precolonoscopy. Moderately abnormal results were obtained for many of the
      parameters studied, in specimens from all the cystic fibrosis children; however
      there were no significant differences between tests on high-dose and low-dose
      enzyme supplements of the same brand in the five children who had duplicate tests
      performed electively. The lavage fluid specimens from two cystic fibrosis
      children were strikingly abnormal in all tests apart from haemoglobin and alpha-1
      antitrypsin. These were two of the three children with DIOS, and were also the
      only cases in the series taking Nutrizym 22. These data suggest that the majority
      of cystic fibrosis children, including those on high-dose enzyme supplements, do
      not have clinically significant colitis, but that there is subclinical mucosal
      inflammation in a minority (two of 17 in this series), for which DIOS and/or
      Nutrizym 22 treatment may be risk factors. Alternatively, inflammation and
      dysmotility in the proximal colon may be directly produced by a drug or other
      agent, producing a clinical syndrome indistinguishable from DIOS. Tests for
      indices of inflammation in gut lavage fluid offer a new approach to the detection
      and measurement of iatrogenic intestinal and colonic injury.

PMID- 8869181
TI  - Stable isotope studies of pancreatic enzyme release in vivo.

PMID- 8869182
TI  - Comparative and experimental pathology of fibrosing colonopathy.
AB  - Although the occurrence of fibrosing colonopathy is temporally associated with
      the introduction of high-strength pancreatic enzyme supplements, its pathogenesis
      remains uncertain. The UK case-control study showed fibrosing colonopathy to be
      associated with high doses of high-strength pancreatic enzyme supplements and
      with a group of brands which occupy only 30% of the market. Two alternative
      hypotheses were proposed to explain the aetiology of fibrosing colonopathy:
      exposure to high levels of enzymes or to as yet unidentified components of the
      formulation. Comparison of the anatomical pathology of fibrosing colonopathy with
      that of previously encountered forms of obstructive gastrointestinal pathology,
      such as stricturing lesions due to potassium chloride preparations and
      nonsteroidal anti-inflammatory drugs, confirmed it to be a previously
      unencountered, long-segment lesion of the colon. Thus the use of the descriptive
      term 'stricture' is a misnomer leading to much clinical confusion when discussing
      obstructive bowel pathology in cystic fibrosis patients. Gavage studies in the
      rat with one of the two monomers (ethyl acrylate) forming the methacrylic acid
      copolymer (Eudragit L30D55) used for the enteric coating of the high-strength
      pancreatic enzyme supplements, have shown pathology comparable to fibrosing
      colonopathy. These findings prompted a series of exploratory studies in
      adolescent pigs. After seven days caecal gavage of Eudragit L30D55 at doses of
      10, 50 or 500 mg/kg/day (comparable to human intake), extensive fibrosing
      colonopathy-like changes, inclusive of dense submucosal fibrosis, were noted at
      all dose levels in seven out of nine animals. Similar studies of the monomer
      components of the Eudragit L30D55 copolymer, at dose levels of 0.015 to 50
      mg/kg/day, representing possible residues in Eudragit L30D55, did not produce
      comparable changes. The conclusion is that, although the precise mechanisms have
      not been elucidated, the role of enteric coatings containing Eudragit L30D55 in
      the pathogenesis of fibrosing colonopathy requires urgent further study.

PMID- 8869183
TI  - The aetiology of fibrosing colonopathy.

PMID- 8869184
TI  - Management of malabsorption in cystic fibrosis: influence of recent developments
      on clinical practice.

PMID- 8869185
TI  - Pancreatic enzymes working party.

PMID- 8869186
TI  - Does it matter if atrial septal defects are not diagnosed in childhood?

PMID- 8869187
TI  - Cystic fibrosis in teenagers and young adults.

PMID- 8869188
TI  - Focal abnormalities detected by 18FDG PET in epileptic encephalopathies.
AB  - A prospective study of 32 children with epileptic encephalopathies 12 years or
      younger revealed a high incidence of focal cortical metabolic defects on 18
      fluorodeoxyglucose positron emission tomography (PET) not suspected from
      clinical, EEG, or magnetic resonance imaging findings. PET scans were normal in
      all five children with typical de novo Lennox-Gastaut syndrome but showed
      cortical metabolic abnormalities in three out of four with atypical de novo
      Lennox-Gastaut syndrome, five out of six with Lennox-Gastaut syndrome following
      infantile spasms, six out of eight with severe myoclonic epilepsy in infancy, one
      out of two with epilepsy with myoclonic-astatic seizures, and four out of six
      with an unclassified epileptic encephalopathy. This suggests that some children
      with epileptic encephalopathies previously thought to have primary generalised
      seizures or seizures due to multifocal pathology may have unifocal cortical
      origin for their seizures. Such an origin may be amenable to surgery.

PMID- 8869189
TI  - Growth and endocrine sequelae of craniopharyngioma.
AB  - The growth and endocrine sequelae of 75 children (33 girls and 42 boys) with
      craniopharyngioma, treated from 1973 to 1994, were studied by retrospective
      review and by follow up assessment in 66 survivors, with a mean time from initial
      surgery of 6.7 years (range 1.5 to 19.8 years). Although infrequently complained
      of, 71% of patients had symptoms to suggest an endocrinopathy at diagnosis. After
      surgery, multiple endocrinopathies were almost universal, such that 75% of
      children had panhypopituitarism at follow up. Hypoadrenal crises in association
      with intercurrent illness contributed significantly to morbidity and mortality,
      as did the metabolic consequences of concomitant antidiuretic hormone (ADH)
      insufficiency and absent thirst. Final height in 25 patients was significantly
      below genetic target height, particularly in the girls, with loss of height
      potential occurring during the pubertal years. The endocrine morbidity associated
      with craniopharyngioma and its treatment remains high but manageable with
      appropriate hormone replacement. However, the combination of ADH insufficiency
      and an impaired sense of thirst following aggressive surgery and severe
      hypothalamic injury remains one of the most complex management problems.

PMID- 8869190
TI  - Evaluation of fasts for investigating hypoglycaemia or suspected metabolic
      disease.
AB  - AIM: To assess the value and safety of fasts for investigating hypoglycaemia or
      suspected metabolic disease. STUDY DESIGN: Review of all diagnostic fasts
      performed over a 2.5 year period. SETTING: The neonatal intensive care unit and
      programmed investigation unit at a tertiary referral centre for endocrinology and
      metabolic disease. RESULTS: 138 diagnostic fasts were performed during the study
      period. Hypoglycaemia (< 2.6 mmol/l) occurred in 54 cases but in only four did
      the blood glucose concentration fall below 1.5 mmol/l. One patient became unwell
      as a result of a fast, but prompt treatment averted any sequelae. Specific
      endocrine or metabolic defects were identified in 30 cases, the most common being
      hyperinsulinism and beta-oxidation defects. CONCLUSIONS: Fasting is safe if
      conducted on an experienced unit with appropriate guidelines. It continues to
      provide useful information for diagnosis and management, particularly in cases of
      hyperinsulinism. Diagnoses should, however, be established by lower risk
      procedures whenever possible. Thus specimens for metabolic and endocrine studies
      should be obtained during the presenting episode and blood acylcarnitine species
      should be analysed prior to fasting.

PMID- 8869191
TI  - Nocturnal hypoglycaemia and sleep disturbances in young teenagers with insulin
      dependent diabetes mellitus.
AB  - OBJECTIVE: To determine the effect of nocturnal hypoglycaemia on sleep
      architecture in adolescents with insulin dependent diabetes mellitus (IDDM).
      DESIGN: 20 adolescents with IDDM (mean age 12.8 years, mean glycated haemoglobin
      (HbA1c) 8.9%) were studied on one night. Plasma glucose was measured every 30
      minutes and cortisol and growth hormone levels every 60 minutes. Sleep was
      recorded using standard polysomnographic montages, and sleep architecture was
      analysed for total sleep time, stages 1-4, rapid eye movement, fragmentation, and
      arousals. RESULTS: Six subjects (30%) became hypoglycaemic (five subjects < 2.5
      mmol/l), with one being symptomatic. There were no differences in age, HbA1c,
      duration of diabetes, or insulin regimen between hypoglycaemic and non
      hypoglycaemic subjects. Hypoglycaemia was not predicted by glucose measurements
      before bed. There was no detectable rise in plasma cortisol or growth hormone
      concentrations during hypoglycaemia. Sleep architecture was not disturbed by
      nocturnal hypoglycaemia with no differences found in sleep stages, fragmentation,
      or arousals. CONCLUSIONS: Nocturnal hypoglycaemia is a common and usually
      asymptomatic complication of treatment in adolescents with IDDM. Moderate
      hypoglycaemia has not been shown to affect sleep architecture adversely. These
      findings are consistent with, and may explain, the observation that severe
      hypoglycaemia, with consequent seizure activity, is more common at night than
      during the day. Counterregulatory hormone responses to nocturnal hypoglycaemia
      may be less marked than with similar degrees of diurnal hypoglycaemia.

PMID- 8869193
TI  - Prevalence, aetiology, and care of severe and profound hearing loss.
AB  - Severe and profound hearing loss (> 70 dB) were analysed in a retrospective study
      of 226 children, born between 1976 and 1985, and recruited from three French
      administrative departments. The prevalence was 0.54 per 1000 children under 9
      years old, with no decrease over the study period. A hereditary origin was
      identified in 20.8% of cases and an infectious origin in 11.5%. Perinatal risk
      factors were present in 11.5%, while the aetiology was undetermined in more than
      half the cases. In 85.8% of the children there was no other severe impairment.
      Marked learning difficulties were observed: 36% of the children were two years
      behind their age group and 28% were more than two years behind. The age of
      initial care decreased over the study period but is still too advanced.
      Systematic neonatal screening would enable earlier care, which should limit the
      social and educational impact of hearing loss.

PMID- 8869192
TI  - Consistency of microvascular and autonomic abnormalities in diabetes.
AB  - The progression of early measures of microvascular disease and autonomic
      neuropathy were studied in a group of 81 children with insulin dependent diabetes
      mellitus over a mean interval of 4.2 years. Repeated measurements were made of
      blood pressure, albumin excretion, joint mobility, and pupillary dilatation in
      darkness. Over the years between the first and the second study, systolic and
      diastolic blood pressure showed positive tracking correlations (r = 0.38 and r =
      0.32) with a small but significant deviation from normality; albumin/creatinine
      ratio was significantly increased (0.79 v 0.55); a greater number of children
      were identified in the second study as having limitation of mobility of the fifth
      metacarpophalangeal joint; and pupillary dilatation in darkness significantly
      decreased (61.5% v 62.9%); 62% of the children with one or more abnormal
      measurements in the first study were found to have measurements outside the
      normal ranges in the second study, indicating a consistency in observations over
      time. It remains to be seen with what accuracy these measurements predict adult
      onset clinical disease.

PMID- 8869195
TI  - Relationship between clinical severity of respiratory syncytial virus infection
      and subtype.
AB  - The relationship between clinical severity of respiratory syncytial virus (RSV)
      infection and distribution of subtype A or B was investigated. The data of 232
      children, who were admitted with RSV infection or diagnosed in the outpatient
      department of the Sophia Children's Hospital, Rotterdam between 1992 and 1995,
      were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence
      assay. Subtyping was performed by an indirect immunofluorescence assay using
      specific monoclonal antibodies. Gender, age at diagnosis, gestational age and
      birth weight, the presence of underlying diseases, feeding difficulties, the
      presence of wheezing and retractions, respiratory rate, temperature, clinical
      diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension
      (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical
      ventilation were observed. Analysis was performed on data from all patients
      diagnosed with RSV infection in the period between 1992 and 1995 spanning three
      RSV seasons, and separately on the RSV season 1993-4. The outcome of the three
      year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with
      the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and
      24 (39.3%) subtype B isolates. None of the variables observed in the season 1993
      4 differed significantly between RSV subtype A and B. Similar results were
      obtained from the analysis in the period 1992 until 1995, with the exception of
      PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more
      retractions were noted in patients with subtype A, p = 0.03). After correcting
      for possible confounders using regression analysis, these differences were not
      significant anymore. The data indicate that there is no relationship between
      clinical severity of RSV infection and subtype.

PMID- 8869194
TI  - Surfactant abnormalities in infants with severe viral bronchiolitis.
AB  - To determine whether abnormalities of pulmonary surfactant occur in infants with
      acute viral bronchiolitis, surfactant indices were measured in lung lavage fluid
      from 12 infants with severe bronchiolitis and eight infants without lung disease.
      Compared with controls, the bronchiolitis group showed deficiency of surfactant
      protein A (1.02 v 14.4 micrograms/ml) and disaturated phosphatidylcholine (35 v
      1060 micrograms/ml) which resolved as the disease improved. Surfactant functional
      activity was also impaired (minimum surface tension 22 v 17 mN/m). These findings
      indicate that surfactant abnormalities occur in bronchiolitis, and may represent
      one of the pathophysiological mechanisms causing airway obstruction.

PMID- 8869196
TI  - Food related, exercise induced anaphylaxis.
AB  - Four children under 12 years of age with food dependent, exercise induced
      anaphylaxis (EIAn) were investigated. These children and five controls performed
      exercise challenges when fasting and one hour after a meal without food suspected
      to predispose to the reaction. Patients then performed exercise tests after
      intake of each suspected food. Three out of 15 food-exercise combination
      challenges were positive, but no reactions were provoked after exercise without
      prior intake of suspected foods. Patients underwent skin prick tests to foods and
      serum total and specific IgE antibodies were measured. Skin prick test results
      were positive and RAST results were positive in two of three instances. In case
      3, food-exercise combination challenges did not provoke any clinical reaction.
      The diagnosis of food dependent EIAn should be considered in young children with
      EIAn of unknown origin.

PMID- 8869197
TI  - A community based study of failure to thrive in Israel.
AB  - OBJECTIVE: To examine the characteristics of infants suffering from failure to
      thrive in a community based cohort in Israel and to ascertain the effect of
      failure to thrive on their cognitive development. METHODS: By review of records
      maintained at maternal and child health clinics in Jerusalem and the two of Beit
      Shemesh, epidemiological data were obtained at age 15 months on a cohort of all
      babies born in 1991. For each case of failure to thrive, a matched control was
      selected from the same maternal and child health clinic. At age 20 months,
      cognitive development was measured, and at 25 months a home visit was carried out
      to assess maternal psychiatric status by questionnaire, and the HOME assessment
      was performed to assess the home environment. RESULTS: 3.9% of infants were found
      to have fallen below the third centile in weight for at least three months during
      the first year of life. Infants with failure to thrive did not differ from the
      general population in terms of obstetric or neonatal complications, birth order,
      or parents' ethnic origin, age, or years of education. The infants with failure
      to thrive did have lower birthweights and marginally smaller head circumferences
      at birth. Developmental assessment at 20 months of age showed a DQ of 99.7 v
      107.2 in the matched controls, with 11.5% having a DQ below 80, as opposed to
      only 4.6% of the controls. No differences were found in maternal psychiatric
      problems as measured by a self report questionnaire. There were, however,
      significant differences in subscales of the HOME scale. CONCLUSIONS: (1) Infants
      who suffered from failure to thrive had some physiological predispositions that
      put them at risk; (2) failure to thrive may be an early marker of families
      providing suboptimal developmental stimulation.

PMID- 8869198
TI  - Outcome of criminal investigation into allegations of sexual abuse.
AB  - The aim was to study the outcome of criminal investigation into allegations of
      sexual abuse made by 160 children assessed over a two year period in a specialist
      paediatric unit in the North of England. In all, 141 of the 160 children (88%)
      were female, and 99 (62%) were aged under 12 years. There were 145 males and nine
      females named by children in allegations of sexual abuse. Fathers formed the
      largest single group of alleged male perpetrators (56/176). None of the nine
      alleged female abusers was prosecuted. Of the 145 males, 57 reached trial; 49
      were convicted, an 86% conviction rate of those sent to trial and a rate of
      proven sexual offence (including cautions) of 44% (54/124) among men originally
      interviewed by the police. Twenty five per cent of children (17/68) who could
      have testified did so, most giving evidence against someone who was known to
      them. Pragmatic selection of cases for prosecution resulted in an outcome highly
      vindicating of the decision to prosecute. The possible effects of this process
      are discussed.

PMID- 8869199
TI  - Male pseudohermaphroditism secondary to panhypopituitarism.
AB  - An infant with a 46XY karyotype was born with ambiguous genitalia, including
      microphallus and perineal hypospadias. A female gender was assigned due to
      extreme failure of development of the external genitalia. Subsequent
      investigations demonstrated panhypopituitarism, and it is believed that severe
      gonadotrophin deficiency was responsible for the intersex state. This case
      illustrates the need to evaluate the hypothalamic-pituitary axis in selected
      cases of intersex, and also questions the prevailing assumption that testosterone
      secretion during embryogenesis is largely pituitary gonadotrophin independent,
      under the control of human chorionic gonadotrophin.

PMID- 8869200
TI  - Injuries and the risk of disability in teenagers and young adults.
AB  - OBJECTIVE: To examine the risk of disability from unintentional injury in
      teenagers and young adults. METHODS: Analyses of data from the National Child
      Development Study, a follow up study of 98% of all children born in England,
      Scotland, and Wales in one week in March, 1958. In 1981, 12,537 study
      participants, 76% of the original cohort, were asked about unintentional injuries
      since age 16 years requiring hospital treatment, and whether these injuries
      resulted in permanent disability. RESULTS: 62% of men and 26% of women reported
      at least one accident since age 16 resulting in injury that required hospital
      treatment. Of these accidents, 3.2% caused permanent disability. The risk of
      disability increased with accident frequency. Injuries requiring hospital
      admission carried the highest risk of disability (9.7%). However, 54% of
      permanent disability reported by men and 74% reported by women resulted from
      injuries treated as outpatients. Road traffic accidents caused 42% of admissions
      and 31% of disability. Fractures constituted 21% of all injuries but were
      responsible for 32% of permanent disabilities. Of the permanent disabilities
      resulting from work related accidents, 82% involved the hand. Of the permanent
      disabilities resulting from accidents in the home, 32% involved the hand.
      CONCLUSIONS: The targeting of prevention strategies towards the major causes of
      injury mortality may have a smaller impact on population levels of injury related
      disability. Non-life threatening injuries, in particular injuries to the hand and
      limb fractures, resulting from accidents in the workplace, the home, and during
      sports, make a significant contribution to the prevalence of permanent injury
      related disability in young adults.

PMID- 8869202
TI  - Serum insulin-like growth factor 1 in congenital heart disease.
AB  - Serum insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding
      protein-3 (IGFBP-3), and a range of growth and nutritional variables were
      investigated in 62 infants with congenital heart disease and healthy controls.
      Infants with congenital heart disease were small, underweight, and had a reduced
      energy intake. Serum IGF-1 and IGFBP-3 concentrations were significantly reduced.
      Decreased IGF-1 and IGFBP-3 levels are observed in nutritional deficiency;
      similar findings in congenital heart disease suggest that undernutrition
      contributes to the poor growth of these infants. Serial measurements of serum IGF
      1 and IGFBP-3 may be helpful in monitoring the effect of nutritional treatment in
      congenital heart disease.

PMID- 8869201
TI  - Antibody responses to Haemophilus influenzae type b conjugate vaccine in sickle
      cell disease.
AB  - OBJECTIVE: To investigate the immunogenicity of Haemophilus influenzae type b
      (Hib) conjugate vaccines in children with sickle cell disease. DESIGN: Open
      study. SETTING: Haemoglobinopathy clinic. SUBJECTS: Children with homozygous
      haemoglobin SS disease (HbSS), sickle haemoglobin C disease (HbSC), and sickle
      beta thalassaemia disease (HbS-beta Thal). INTERVENTIONS: Children over the age
      of 2 years received a single dose of Hib-tetanus toxoid conjugate vaccine (PRP
      T). MAIN OUTCOME MEASURES: Antibody response to Hib polysaccharide (PRP)
      approximately one month after vaccination. RESULTS: 77 children over the age of 2
      years were studied,, 55 with HbSS, 16 with HbSC, and six with HbS-beta Thal.
      Before vaccination, 44% had anti-PRP IgG titres less than the level associated
      with long term protection (1.0 microgram/ml). After a single dose of PRP-T all
      children mounted an antibody titre > 1 microgram/ml. Geometric mean anti-PRP IgG
      titre achieved postvaccination (45.2 micrograms/ml 95% confidence interval (CI)
      31.6 to 64.8) was comparable to that of a healthy population. Children with HbSC,
      however, had a significantly higher antibody titre postvaccination (91.1
      micrograms/ml; 95% CI 32.7 to 254.4) than the children with HbSS (36.7
      micrograms/ml; 95% CI 25.1 to 52.9). CONCLUSIONS: Children with a diagnosis of
      sickle cell disease who are over the age of 2 years make a vigorous antibody
      response to a single dose of PRP-T vaccine and hence we suggest unimmunised
      individuals in this group should receive a single dose of a Hib conjugate
      vaccine.

PMID- 8869203
TI  - Mobility status and bone density in cerebral palsy.
AB  - The spinal bone mineral density (SBMD) and calcaneal broadband ultrasound
      attenuation (BUA) was measured in 27 children with cerebral palsy. They were
      categorised into four mobility groups: mobile with an abnormal gait, mobile with
      assistance, non-mobile but weight bearing, non-mobile or weight bearing. Mean SD
      scores for BUA and SBMD differed among mobility groups (analysis of variance, p <
      0.001 and p = 0.078, respectively).

PMID- 8869204
TI  - Integrated care pathways.

PMID- 8869205
TI  - ECG and echocardiographic diagnosis of pulmonary thromboembolism associated with
      central venous lines.

PMID- 8869206
TI  - Persistent nocturnal cough in childhood: a population based study.

PMID- 8869207
TI  - Sodium/glucose cotransporter activity in cystic fibrosis.

PMID- 8869208
TI  - Haemoglobin values in venous and skin puncture blood.

PMID- 8869209
TI  - Challenges in the management of childhood brain tumour.

PMID- 8869210
TI  - Paediatricians' knowledge of cardiac arrest guidelines.

PMID- 8869211
TI  - Sleeping position and cot death.

PMID- 8869212
TI  - Uses and abuses of pulse oximetry.

PMID- 8869213
TI  - Calcium supplementation for the prevention and treatment of osteoporosis.

PMID- 8869214
TI  - HLA-DR genotyping, diagnosis and prognosis of inflammatory arthritis.

PMID- 8869215
TI  - Anti-vascular endothelial cell antibodies (AECA): comparison of two assay methods
      and clinical applications.
AB  - Vascular endothelial cells may be a target for autoantibodies (AECAs) against
      membrane antigens that are constitutively expressed, induced or bound to their
      surface. To test this hypothesis, we used an enzyme-linked immunosorbent assay
      (ELISA) with two types of human endothelial cells as the substrate, i.e., human
      umbilical cord vein endothelial cells (HUVECs) or the hybrid cell line EAhy-926
      obtained by fusion of HUVECs with the bronchial carcinoma cell line A549. A
      comparative functional study of these two cell types demonstrated that EAhy-926
      cells produced only small amounts of VIII von Willebrand factor and tissular
      factor, did not contain Weibel Palade bodies visible under the electron
      microscope, and expressed ICAM-1 and selectin E in levels of no more than 15% of
      those expressed by human umbilical cord vein endothelial cells both after
      stimulation by bacterial lipopolysaccharide and under basal conditions. However,
      the two assay methods yielded similar IgG AECA titers when used on sera from
      patients with rheumatoid vasculitis or antiphospholipid syndrome. These
      antibodies did not exhibit cytotoxicity for cord vein or EAhy-926 cells. They
      were not specific for endothelium, since their activity decreased by a mean of
      40% after incubation of sera with the epithelial cell line A549. A cross
      sectional study of 565 sera demonstrated that anti-vascular IgG and IgM AECAs
      reactive with EAhy-926 cells occurred mainly in patients with dermatomyositis
      (IgG, 58%; IgM, 22%), systemic scleroderma (IgG, 48%; IgM, 18%), primary
      Sjogren's syndrome (IgG, 44%; IgM, 12%) and secondary and primary systemic
      vasculitides (IgG, 38%; IgM, 18%) including Wegener's granulomatosis. A
      longitudinal study in patients with Wegener's granulomatosis showed that AECAS
      were predictive of disease activity.

PMID- 8869216
TI  - Adult Still's disease: part I. Manifestations and complications in sixty-five
      cases in France.
AB  - DESIGN: a retrospective multicenter study conducted in France identified 65 cases
      of adult Still's disease. Data were recorded on a standardized questionnaire
      validated by the Inflammatory Joint Disease and Immunorheumatology Committee of
      the Societe Francaise de Rhumatologie. OBJECTIVES: (1) To compare clinical and
      laboratory findings in our patients with those reported in earlier studies,
      particularly two large series from Canada and Japan, respectively; (2) to
      describe the systemic and visceral complications associated with adult Still's
      disease. RESULTS: as compared with the two above-mentioned series, our study
      group included more patients who had experienced onset of their disease after the
      age of 35 years and fewer patients with involvement of the liver, spleen, or
      lymph nodes. Rates of occurrence of arthritis, myalgia, sore throat, pleuritis,
      pericarditis, and abdominal pain were significantly higher in the Canadian series
      than in the other two series. Arthritis was absent in one fourth of our patients.
      Life-threatening complications included "Still's hepatopathy", disseminated
      intravascular coagulation (with hemophagocytosis in some cases), and "Still's
      myocarditis". CONCLUSION: differences in the expression of adult Still's disease
      were found between patients from Canada, France, and Japan. Adult Still's disease
      can be responsible for life-threatening complications.

PMID- 8869217
TI  - Adult Still's disease. Part II. Management, outcome, and prognostic factors.
AB  - DESIGN: a multicenter study conducted in France identified 65 cases of adult
      Still's disease. Follow-up exceeded one year in 52 cases. OBJECTIVES: were as
      follows: 1) to describe treatments used; 2) to analyze disease course patterns;
      3) to study joint alterations; 4) to determine whether any characteristics
      present within the first six months of onset were of prognostic significance.
      RESULTS: aspirin was ineffective. Indomethacin ensured satisfactory control in
      eight patients. Corticosteroid therapy was required in 88% of cases. Among
      patients followed up for more than one year, half developed radiologic joint
      alterations; 23% had monocyclic systemic disease, 38.5% had polycyclic systemic
      disease and 38.5% had chronic articular disease. More than half of the patients
      (58%) had more than one systemic flare. Polyarthritis at onset and involvement of
      the proximal limb joints were significantly predictive of chronic articular
      disease, whereas isolated arthralgia was predictive of monocyclic or polycyclic
      systemic disease. Oligoarthritis was not predictive of the outcome. CONCLUSION:
      the knowledge that polyarthritis or proximal limb joint involvement within six
      months of onset is predictive of chronic joint disease may have important
      therapeutic implications.

PMID- 8869218
TI  - Lactose intolerance and osteoporosis in men.
AB  - Three men with osteoporotic fractures were found to have lactase deficiency and
      low dietary calcium intakes, decreased urinary calcium, and moderately increased
      serum osteocalcin and parathyroid hormone levels. Histomorphometric studies
      demonstrated increases in osteoid parameters and resorption surfaces. The few
      studies of the links between osteoporosis and lactase deficiency have yielded
      discordant results. A low calcium intake due to aversion to dairy products caused
      by the lactase deficiency may promote the development of osteoporosis.

PMID- 8869219
TI  - Time course of radiologic lesions in spinal hyperostosis: an osteoradiometric
      study.
AB  - The purpose of this study was to evaluate changes over time in the flowing spinal
      ossification characteristic of spinal hyperostosis. Thirty-two patients were
      studied. A QR-ORM osteoradiometry apparatus was used to measure variations in the
      surface area of the ossification on radiographs obtained after three, ten, and 20
      years. The size of the ossification increased gradually in every case. Patients
      with a small ossification on the initial radiograph and younger patients were
      more likely to have larger ossification size increases over time; male gender and
      diabetes mellitus had a similar effect, although the differences were not
      significant, perhaps because of the small number of subjects. The magnitude of
      the ossification increase was not the same on the anteroposterior and lateral
      films at the various time points. The rate of ossification increase was slower in
      patients with long-standing disease or osteoporosis, although differences were
      not statistically significant. Over time, the density of the ossification
      increased, particularly near the vertebral bodies, perhaps as a result of
      transformation of fibrocartilage tissue into compact bone tissue.

PMID- 8869220
TI  - Rheumatism as perceived by some quotations: as seen by the patient and physician.
AB  - The word "rheumatism", introduced in ancient times, is still used directly or
      indirectly, in parallel with the terms of the modern nosography. The reasons for
      this persistence can be sought in the history of the concept, which can be
      approached via quotations from texts written either by authors who describe
      popular beliefs or their own sufferings; or by physicians known to have played a
      prominent role in the individualization of rheumatology. The word "rheumatism"
      was first used mainly to designate a painful fluxion of the tissues located
      between the skin and the internal organs. It gradually lost ground to more
      descriptive terms suggestive of joints. Thus, the concept of "rheumatism" still
      bears the hallmark of its "popular" roots and is on a level parallel to but
      distinct from that of modern nosography. Awareness of its origins may improve
      communication between physicians and patients and also raises questions about the
      foundations of the concept of "rheumatic disease".

PMID- 8869221
TI  - Methods for quantitative analysis of trabecular bone structure.
AB  - Bone mineral density accounts for 70% to 80% of the mechanical resistance of bone
      but is unrelated to bone tissue structure. The vertebral fracture risk increases
      with advancing age irrespective of whether or not bone mineral density decreases,
      suggesting that changes in bone microarchitecture contribute significantly to the
      development of osteoporosis. In contrast to bone mass, bone architecture is
      difficult to evaluate. Among the various methods developed to investigate bone
      structure, biomechanical studies are of limited value since they are done on
      cadaver bones. Measurement of microarchitectural parameters (e.g., mean
      trabecular thickness, density and separation) in bone specimens obtained by
      needle biopsy is the gold-standard technique. Parameters reflecting trabecular
      interconnections (e.g., total number of nodes and free ends) can also be measured
      on needle biopsy specimens. New techniques of as yet unproven validity include
      star volume and trabecular bone pattern factor measurement. Noninvasive
      techniques capable of supplying qualitative information about bone tissue are
      also under study. Ultrasonography can theoretically provide data on bone
      microarchitecture but has not yet been proven useful in clinical practice.
      Statistical, structural, or fractal analysis techniques can be used to evaluate
      bone texture on digitized roentgenograms, computed tomography sections, or
      magnetic resonance imaging displays; although this approach holds great promise,
      it is still under evaluation and has not yet been compared with histomorphometry.
      Lastly, the apparent relaxation time of bone marrow determined using magnetic
      resonance imaging may also provide information on bone structure.

PMID- 8869222
TI  - Recurrent psoriatic onychoperiostitis induced by hydroxychloroquine.
AB  - Synthetic antimalarial agents can cause exacerbation of latent or patent
      psoriatic skin lesions. A case of psoriatic onychoperiostitis precipitated by
      hydroxychloroquine therapy is reported. The patient had primary Sjogren's
      syndrome, raising questions about the incidence and causation of the ungual
      abnormalities associated with this condition.

PMID- 8869223
TI  - Vertebral osteomyelitis due to Capnocytophaga.
AB  - The first case of vertebral Capnocytophaga infection in an immunocompetent
      subject is reported. The patient was a 75-year-old woman with low back pain and a
      decline in general health. Plain roentgenograms disclosed erosions in the upper
      endplate of L4 and the lower endplate of L3 with no lesions of the intervening
      disk. Magnetic resonance imaging confirmed that the disk was normal. The organism
      was identified only by a repeat vertebral biopsy with bacteriologic cultures in a
      CO2-enriched atmosphere. The patient achieved a full recovery. Patients with
      suspected bone infections should be evaluated for portals of entry
      (Capnocytophaga is a normal inhabitant of the oral cavity) and should undergo
      multiple microbiological studies aimed at detecting a broad range of organisms.

PMID- 8869224
TI  - Adult-onset Klippel-Feil syndrome with inaugural neurologic symptoms: two case
      reports.
AB  - Two cases of adult-onset Klippel-Feil syndrome with inaugural neurologic
      manifestations are reported. Increased awareness of this infrequent syndrome
      would improve the early diagnosis of the potentially fatal or disabling
      congenital defects associated with Klippel-Feil syndrome.

PMID- 8869225
TI  - Psoas abscess complicating Crohn's disease.

PMID- 8869226
TI  - Cauda equina syndrome caused by osteosarcoma in a patient with Paget's disease of
      bone: value of modern imaging.

PMID- 8869227
TI  - Tiopronin-induced polymyositis.

PMID- 8869228
TI  - Joint sparing in a rheumatoid arthritis patient with an inherited peripheral
      neuropathy.

PMID- 8869229
TI  - Acquired protein S deficiency with primary antiphospholipid syndrome and
      recurrent thrombotic events: report of a case.

PMID- 8869230
TI  - Sensitivity to change of various techniques for measuring radiologic severity of
      hip osteoarthritis.

PMID- 8869231
TI  - [Regulation of cardiac calcium current by cGMP/NO route].
AB  - Early studies in whole heart indicated that cGMP antagonized the positive
      inotropic effects of catecholamines and cAMP. Since the L-type Ca2+ channel
      current (ICa) plays a predominant role in the initiation and development of
      cardiac electrical and contractile activities, regulation of ICa by cGMP pathways
      has received much attention over the last ten years. Patch-clamp measurements of
      ICa in isolated cardiac myocytes reveal at least three different cGMP effectors
      that may participate to different degrees in different animal species and cardiac
      tissues in the regulation of ICa by cGMP. In frog ventricular myocytes, cGMP
      inhibits ICa by stimulation of a cGMP-stimulated cAMP phosphodiesterase (PDE2),
      whereas in rat ventricular myocytes, cGMP predominantly inhibits ICa via a
      mechanism involving activation of a cGMP-dependent protein kinase (cGMP-PK). In
      guinea pig, frog and human cardiomyocytes, cGMP can also stimulate ICa via an
      inhibition of a cGMP-inhibited cAMP phosphodiesterase (PDE3). This effect is most
      predominant in human atrial myocytes and appears readily during an activation of
      the soluble guanylate cyclase activity by low concentrations of nitric oxide (NO)
      donors. Biochemical characterization of the endogenous phosphodiesterases and
      cGMP-PK in purified cardiac myocytes provide further evidence in support of these
      mechanisms of cGMP action on ICa. However, the regulation of cGMP levels by a
      variety of agents is not always consistent with their effects on contractility.
      In particular, the participation of cGMP and NO pathways in the regulation of
      cardiac ICa and contractility by acetylcholine is still questionable.

PMID- 8869232
TI  - [Beta adrenergic signal transduction and heart adenyl cyclase].
AB  - Transduction of the beta-adrenergic signal plays an important role in the
      regulation of cardiac contractility. It is mediated by three sarcolemmal
      proteins: the beta-adrenergic receptor, G proteins and adenylyl cyclase which is
      the catalytic unit of the system which generates cAMP, the second messenger of
      the system. Each protein comprises a number of isoforms which yields a wide range
      of potential regulations, many of which are not yet elucidated. Among the three
      proteins, the adenylyl cyclase is the one which has been less studied. However,
      the recent cloning of many of its isoforms allows now investigations of their
      expression in many tissues and cell types. We have shown in rats that among the
      five isoforms detected in the myocardium, type V and VI adenylyl cyclase mRNAs
      are the most abundant ones. Type V and VI adenylyl cyclase mRNA abundance is
      similar in late fetal hearts. Type V mRNA accumulates in the heart during
      postnatal development whereas type VI mRNA concentration remains unchanged.
      Consequently, type V mRNA becomes highly predominant compared to type VI mRNA in
      the adult rat ventricle (type V/type VI adenylyl cyclase mRNAs approximately 10).
      Whatever the developmental stage, cardiac adenylyl cyclase activity is inhibited
      by submicromolar calcium concentrations. In adult ventricles, adenylyl cyclase
      activity in the presence of 1 mM ATP is at least three times higher than that
      observed in fetal and new born rat hearts. Since this increase parallels the
      accumulation of type V adenylyl cyclase mRNA, one can hypothesize that the former
      is due to the latter. In contrast, our preliminary results seem to indicate that
      during heart failure in rats, decreased adenylyl cyclase activity is not
      associated with decreased cardiac concentrations of type V and VI adenylyl
      cyclase mRNAs. Isoform specific antibodies are now required to understand the
      reasons for such discrepancy.

PMID- 8869233
TI  - [Molecular aspects of the diversity of cardiovascular calcium channels].
AB  - Voltage-dependent calcium channels control various physiological functions such
      as the excitation-contraction coupling, the secretion of hormones or the release
      of neurotransmitters in the nervous system. Molecular genetics has allowed to
      provide a structural basis to the functional diversity of calcium channels and to
      initiate studies to understand the relations between the structure and the
      function of these excitable proteins. The aim of our research is to compare both
      the functional and structural properties of calcium channels from various
      tissues. The studies on dissociated or cultured cells allow to describe their
      properties, regulation, pharmacology and pathophysiology in native tissues.
      Structure-functions studies using reconstitution models such as Xenopus oocytes
      aim to understand the molecular basis underlying their diversity. Calcium
      channels are composed of several subunits (alpha 1, alpha 2-delta, beta, gamma).
      Six genes have been identified as coding for the pore subunit (alpha 1) which
      determines the general profile and in particular the pharmacology of a given
      calcium channel. However, the auxilliary subunits and mainly beta subunits for
      which 4 genes and several variants have been isolated, are able to modify the
      level of expression and the properties of a calcium current directed by an alpha
      1 subunit in a reconstitution model. The structure-function studies are now
      mainly designed to investigate the functional consequences of the interaction
      alpha 1-beta on the electrophysiological and pharmacological properties. These
      studies should lead to a better understanding of the molecular basis underlying
      the diversity between cardiac and vascular calcium channels and also of their
      respective implication in pathophysiology. The co-expression of several families
      of calcium channels in a single neuron do not allow properly to investigate the
      properties and the regulation (by phosphorylation or G proteins) of the neuronal
      calcium channels which are involved in neurosecretion. The use of reconstitution
      models will provide a better characterization of neuronal calcium channels and
      should help to the development of new drugs of therapeutical interest.

PMID- 8869234
TI  - [Regulation of muscarinic potassium channels].
AB  - Inwardly rectifying muscarinic potassium channels are directly activated by M2
      muscarinic receptors in heart via a Pertussis toxin-sensitive G-protein. An
      intracellular second messenger is not involved in their activation. These
      channels undergo rapid (in about 30 seconds) and short-term desensitization. This
      desensitization is reversible in about 5 minutes. The molecular events underlying
      muscarinic potassium channels desensitization are still under study and
      apparently involve a phosphorylation/dephosphorylation process of one the
      proteins, i.e. the receptor, the G-protein or the channel itself.

PMID- 8869235
TI  - [Calcium signal and contraction].
AB  - The calcium ion plays a unique role as a messenger and a cofactor in cardiac
      contraction. This role relies on the strict control by the cell of Ca
      homeostasis, the components of which are described in this review. During the few
      last years, tools for the measurement of free intracellular Ca in living cells
      have been developed which include: probes (aequorin, Fura 2, Indo 1, Fluo 3...),
      tools for the loading of the cells (microinjection and AM-probes) and systems to
      analyze the signal (photometers, microfluorimeters, confocal microscopy). Those
      tools allowed the analysis of calcium signal in cardiomyocytes. In the cardiac
      cell, activation of a Ca influx through L type Ca channels is usually considered
      as the pathway initializing Ca mobilization and leading to contraction. It has
      now been demonstrated that this pathway is activated by beta 1-adrenergic
      agonists via cyclic AMP. However, amplification of contraction may involve other
      targets. Thus, the positive inotropic effect of beta 2-adrenergic agonists is
      also associated with a rise in cytosolic Ca but is not linked to cyclic AMP
      increase. The alpha 1-adrenergic pathway involves a sensitization of myofilaments
      for Ca, and increases contraction without an increase in cytosolic Ca. Finally,
      the positive inotropic effect of glucagon combines the cyclic AMP pathway with a
      cyclic AMP independent pathway triggered by the metabolite mini-glucagon.

PMID- 8869236
TI  - [Microtubules: functional polymorphisms of tubulin and associated proteins
      (structural and motor MAP's)].
AB  - In neuronal cells, microtubules are built from a very large number of alpha- and
      beta-tubulin variants. This diversity is due to the expression of a multigene
      family and to a combination of several original posttranslational modifications.
      Similarly, structural and motor microtubule-associated proteins, which regulate
      the assembly of microtubules, the modeling of their network and the mediation of
      their functions, are also very heterogeneous. As a consequence, mixing of these
      two protein polymorphisms leads to the formation of functionally-distinct
      microtubules. We have shown that polyglutamylation, the major posttranslational
      modification of neuronal tubulin, was used as a progressive regulator in the
      binding of structural and motor microtubule-associated proteins, in modulating
      gradually the conformation of the tubulin carboxy-terminal domain, playing thus a
      crucial role in microtubule dynamics.

PMID- 8869237
TI  - [Neuronal intermediate filament proteins].
AB  - The characteristics of the seven intermediate filament proteins expressed during
      the development of neurons are reviewed. The most extensively studied have been
      neurofilament proteins (NFP) and peripherin. The relative plasticity of the
      peripherin network can account for its possible role during development when the
      axons of the neurons in which this protein is expressed have to find their
      targets crossing a non-neural environment probably in answer to signals from this
      environment and from their respective targets. Peripherin may assume a similar
      role when axons regenerate. NFP are considered as maintaining the axonal caliber,
      thus ensuring a normal axonal transport. Their network is highly disrupted in
      several diseases, particularly in motor neuron diseases. Mice transgenic for
      human NFP or in which mouse NFP are overexpressed have been obtained and are
      considered as animal models for these diseases.

PMID- 8869238
TI  - [Pharmacological modulation of alterations of endothelial cytoskeleton induced by
      hydrogen peroxyde and by TNF-alpha].
AB  - New selenium containing compounds which act as mimics of glutathione peroxidase
      (GPx) protect vascular endothelial cells (HUVEC) from the toxicity of 140 microM
      hydrogen peroxide. In the absence of GPx mimic, hydrogen peroxide destroys the
      tightness of the cellular monolayer and transforms the actin network into compact
      stress fibers. The pre-treatment of the cells by 4 microM of the lead-compound
      BXT-51072 for 1 hours inhibits the morphological modifications induced by
      hydrogen peroxide. This GPx mimic can also prevent the alterations of the
      endothelial cytoskeleton which are induced by Tumor Necrosis Factor-alpha (TNF
      alpha) and which consist in a reorganization of actin filaments with the
      formation of stress fibers. Fluorescent labeling of polymerized actin has been
      performed by means of phalloidine coupled with rhodamine. The protective effect
      of this antioxidant catalyst against the toxicity of hydrogen peroxide and TNF
      alpha includes the maintenance of a structural configuration of the cytoskeleton
      which is required for the function of endothelial barrier.

PMID- 8869239
TI  - [Activity of glyoxylate cycle during the culture of Rhodotorula gracilis in the
      presence of fatty acids and detergents].
AB  - In this work on Rhodotorula gracilis, we studied the level of the representative
      enzymes of foundamental metabolic ways (HK, PK, G6PDH and IDH) and those of ICL
      and MS key enzymes of glyoxylate cycle with different carbone sources. The
      glucose appears the best source of carbone for all the tested enzymes except ICL
      and MS which are practically absent in the cells developed with this carbone
      source. In presence of acetate and ethanol we have obtained the expression of the
      glyoxylate cycle enzymes (ICL and MS). Moreover we obtained the operativity of
      the glyoxylate cycle in the lipid-rich cells or cells developped on neutral
      detergents or anionics similar to the fatty acids.

PMID- 8869240
TI  - [Origin of the adenohypophysis and of the olfactory system in toads:
      demonstration by chimera method].
AB  - Localisation of the primordium of the olfactory system and its topographical
      relationships with the primordium of the hypothalamic-hypophyseal system were
      determined on the embryos of the toad Bufo japonicus by generating chimeric
      embryos. Different parts of the neural ridge and the neural plate were taken up
      from normal embryos and grafted on the same region of albino embryos of the same
      developmental stage. The melanin granules contained in the grafts permitted to
      trace the developmental fate. The anteriormost region of the neural ridge (ANR)
      was found to be the origin of all the parts of the adenohypophysis as well as
      some of the neurons in the preoptic region. The infundibulum differentiated from
      the central portion of the neural plate, just posterior to the adenohypophyseal
      primordium. The primordium of the olfactory system, including the olfactory sacs
      and the olfactory bulbs, was found to be situated on the neural ridge on both
      sides of the ANR. The present results showed that the central and peripheral
      parts of each of the two systems constitute a closely apposed cell population at
      the neurula stage. It seems that the periphero-central connection in these
      systems reflect a clonal origin of the presumptive cells. If the olfactory
      primordium was removed at the neurula stage, the olfactory sac regenerated from
      the adenohypophyseal primordium. In conclusion, these results demonstrate that
      the olfactory primordium is related not only topographically but also
      ontogenetically to the adenohypophyseal primordium.

PMID- 8869241
TI  - [Definitions and classification of cardiomyopathies].

PMID- 8869242
TI  - [Segmental rehabilitation in cardiac failure: short and long-term results].
AB  - Many patients with chronic cardiac failure may benefit from exercise
      rehabilitation. However, the usual protocols, which may lead to haemodynamic
      disturbances or induce arrhythmias, are rarely applicable in the most severe
      cases. Therefore, the authors developed a protocol of segmental rehabilitation
      where the same muscle groups as in global readaptation are involved, but
      successively and not simultaneously. This study included 25 patients in the NYHA
      class III. Many parameters were analysed before and after forty sessions.
      Although the resting isotopic ejection fraction (0.26 +/- 0.1 vs 0.27 +/- 0.11; p
      = NS), oxygen consumption at the ventilatory threshold (14.3 +/- 3.5 vs 18.3 +/-
      5.2 ml/kg/min; p = NS) or at peak effort (17.4 +/- 4.7 versus 18.3 +/- 5.2
      ml/kg/min, p = NS) were unchanged, three other parameters were significantly
      improved: the duration of exercise (9.2 +/- 2.4 vs 10.4 +/- 3.4 min; p < 0.02)
      maximum work load (3 046 +/- 1 510 vs 3 992 +/- 2 482; p < 0.01) and muscular
      force (151 +/- 35 versus 220 +/- 41 kg; p < 0.0001). In addition, after a follow
      up period of 43 +/- 18 months, a close inverse relationship was observed between
      the gains obtained in terms of duration of exercise and maximum work load and the
      number of hospital readmissions. Similarly, the 10 patients having undergone
      rehabilitation with this protocol had 11.7 times fewer hospital readmissions than
      the other 15. Segmental rehabilitation would therefore seem to be a safe
      technique for patients with severe cardiac for significantly increasing exercise
      capacity and lowering the number of readmissions to hospital.

PMID- 8869244
TI  - [Apparently idiopathic chronic pericardial effusion. Long-term outcome in 71
      cases].
AB  - Seventy one cases of apparently idiopathic chronic pericardial effusion were
      systematicaly followed up. There were 3 inclusion criteria: patients had to be
      symptomatic with radiological cardiomegaly without tamponade or an acute onset;
      the effusion had to be stable for more than 3 months despite medical therapy at
      the time of surgery; the parietal pericardium removed at surgery had to be of
      normal histopathological appearances. Cases with a discernable classical cause of
      pericardial effusion were excluded: previous mediastinal radiotherapy, connective
      tissue diseases, malignancies, chronic infection or a recent episode of acute
      pericarditis. There were 9 deaths during the first five postoperative years, one
      of which was related to the pericardial disease and surgery. By definition, no
      cause was found but in one third of cases a relationship between the pericarditis
      and other disease processes was possible. The management of these large
      pericardial effusions resistant to treatment without any apparent underlying
      pathology and in which echocardiography only shows a large effusion should be
      surgical with drainage of the pericardial cavity, allowing exclusion of
      aetiologies which are non-identifiable by other methods, with a negligeable
      operative risk even in elderly patients and good long-term clinical results. This
      recommendation is based on systematic follow-up of over 5 years in 57 of our 71
      cases; after drainage, only one of the nine deaths observed was related to the
      pericardial disease itself and 59, subjects (83%) had no further symptomatic
      pericardial disease.

PMID- 8869243
TI  - [Angioplasty of the proximal left anterior descending artery outside the acute
      phase of myocardial infarction. Apropos of a series of 100 consecutive patients].
AB  - The indications of percutaneous transluminal coronary angioplasty (PTCA) of the
      proximal left anterior descending artery (LAD 1) must take into consideration the
      importance of the threatened myocardial territory in case of complications and
      the supposedly increased risk of restenosis of this arterial segment. One hundred
      consecutive patients (average age 59.9 +/- 11.4 years with 77% of men) outside
      the acute phase of myocardial infarction were included in this retrospective open
      study from January 1st 1988 to March 1st 1992. There were 76 cases of single
      vessel. The average left ventricular ejection fraction was 64.8 +/- 12%. During
      the hospital period, there were no deaths. 1 myocardial infarction despite
      emergency coronary bypass surgery, and 2 programmed coronary bypass procedures.
      During follow-up, "clinical restenosis" as defined by the authors was observed in
      29.7% of cases; 1 patient died of cardiovascular causes, 18 had a repeat PTCA
      with a success rate of 100%. The clinical restenosis rate of repeat PTCA was 33%.
      One patient underwent a third PTCA with a successful outcome. Ten coronary bypass
      procedures were necessary. Restenosis was more common after PTCA of lesions
      situated on a bifurcation and when high inflation pressures had to be used.
      Restenosis was constant after repeat PTCA when the initial restenosis occurred
      before the 60th day.

PMID- 8869245
TI  - [Estimation of left ventricular volumes and ejection fraction with acoustic
      quantification in myocardial infarction. Comparison with echocardiographic,
      angiographic and scintigraphic data].
AB  - The object of this study was to assess the reliability of measurements of left
      ventricular volumes and ejection fraction by acoustic quantification by the
      method of summation of discs in acute myocardial infarction. Thirty-two patients
      with an average age of 55.9 +/- 12 years were studied prospectively on average 6
      +/- 2 days after the onset of myocardial infarction. Within 48 hours, the
      patients underwent TM echocardiography (Teichholz's method) two-dimensional
      echocardiography (Simpson's method on freeze frames and acoustic quantification)
      before left ventricular angiography and isotopic ventriculography, considered as
      the reference methods for comparing left ventricular volumes and ejection
      fractions. The data displayed in real time by acoustic quantification correlated
      well with the results of left ventricular angiography (r = 0.77; p = 0.0001) and
      moderately underestimated (+4.1 +/- 11.9%) the ejection fraction, but were
      relatively disappointing for estimating volumes. When compared with isotopic
      ejection fraction, the correlation coefficient was r = 0.71 (p = 0.0004) and the
      values were overestimated. In this study, acoustic quantification was the most
      reliable echocardiographic method of assessing the left ventricular ejection
      fraction with reference to contrast angiography (Teichholz: r = 0.56; p = 0.0014;
      Simpson: r = 0.76; p = 0.001). The authors conclude that assessing the left
      ventricular ejection fraction with acoustic quantification is reliable in acute
      myocardial infarction. However, the method is not very accurate in measuring end
      systolic and end diastolic volumes.

PMID- 8869246
TI  - [Treatment and prognosis of tachyarrhythmia after atrial surgical repair of
      transposition of great vessels].
AB  - The Mustard and Senning procedures may be complicated by atrial tachyarrhythmias.
      In order to determine their prognosis, the authors undertook a review of the 288
      patients operated and followed up in their department. Thirty-six (12.5%) had
      documented atrial tachycardias. In 13 cases, Holter monitoring showed bursts of
      atrial tachycardia. In the other 23 cases, the tachycardia was sustained and
      often caused severe symptoms (syncope). Reduction of the sustained forms was
      obtained by rapid atrial pacing, cardioversion or amiodarone therapy. After
      restoration of sinus rhythm, several therapeutic protocols were used, often in
      the same patient: abstention, leading to 5 recurrences in 6 cases; treatment with
      betablockers in 12 patients with well tolerated or exercise-induced atrial
      tachycardia with 11 successes; amiodarone, with 4 relapses out of 5 when the
      dosage was less than 200 mg/m2/day and 13 successes out of 18 when the dosage was
      200-250 mg/m2/day. During a follow-up of 1 to 19 years, 6 severe complications
      (neurological sequellae, cardiac failure), and 6 deaths, were observed. All these
      patients were poorly controlled and continued to be have tachyarrhythmias. The
      authors conclude that tachyarrhythmias are neither rare nor always symptomatic,
      so justifying their systematic investigation. They should be reduced by oral
      amiodarone or rapid atrial pacing depending on the clinical urgency, never by
      intravenous antiarrhythmics which can be dangerous. The poor prognosis associated
      with tachyarrhythmias makes their control essential either with betablockers or
      good doses of amiodarone, eventually covered by permanent cardiac pacing.

PMID- 8869247
TI  - [Techniques of correction of partial right abnormal pulmonary venous return
      associated with atrial septal defect].
AB  - Many techniques have been described for correcting partial right anomalous
      pulmonary venous drainage to avoid the possible complications of stenosis of the
      systemic or pulmonary venous return, residual shunt or arrhythmias. Between 1985
      and 1994, 33 patients aged 1 to 69 years underwent repair of this malformation.
      The anomalous drainage was situated at the cavo-atrial junction or above in 25
      cases and to the right atrium in 8 cases. Depending on the level of the drainage
      of the anomalous pulmonary veins, the size of the superior vena cava, the site of
      atrial septal defect and the age of the patient, 3 techniques were used: simple
      tunneling, tunneling with widening of the superior vena cava by a patch,
      tunneling with section of the superior vena cava and its transposition to the
      right atrium. There was no hospital mortality. Postoperative echocardiography
      showed a minimal residual shunt which regressed at the two months control
      examination. No cases of restriction of the systemic or pulmonary venous return
      were observed. Six patients developed arrhythmias during the hospital period. At
      the end of follow-up, all patients were asymptomatic without residual shunts or
      restriction of venous drainage. Persistent arrhythmias were observed in one case
      (3%). There were no differences in the results of the three techniques used. By
      using the most appropriate technique of repair for the anatomical form allows
      correction of this malformation with the minimal number of postoperative
      complications.

PMID- 8869248
TI  - [Risk of mortality after myocardial infarction: value of heart rate, its
      variability and left ventricular ejection fraction].
AB  - Heart rate variability is a useful parameter for risk stratification after
      myocardial infarction. However, the relationship between heart rate itself and
      its variability has not been adequately studied. The authors compared the average
      RR interval of 24 hours recorded by Holter monitoring with the variability of
      heart rate and of left ventricular ejection fraction to assess the risk of death
      after myocardial infarction. A total of 579 patients was followed up for 2 years
      after acute myocardial infarction. During this period, there were 54 deaths, 42
      of cardiac origin, 26 being classified as sudden death. The positive predictive
      value of left ventricular ejection fraction was lower than those of mean RR
      interval and the variability of heart rate for overall mortality, cardiac
      mortality and sudden death. The three indices were essentially equivalent for the
      prediction of non-sudden cardiac death. The positive predictive value of heart
      rate variability was better than the mean RR interval for sensitivities < 40%,
      for all cause mortality. However, for sensitivities > 40%, the two parameters
      were equivalent or slightly in favour of the mean heart rate over 24 hours. The
      authors conclude that the mean RR interval over 24 hours is an important
      prognostic index after myocardial infarction. This index is more powerful than
      left ventricular ejection fraction and comparable to heart rate variability.

PMID- 8869249
TI  - [Incidence of atrial arrhythmia in patients with long term dual-chamber
      pacemakers. Contribution of the Holter function of pacemakers].
AB  - The extension of the RAM memories in the latest generation of pacemakers has
      enabled development of Holter function allowing continuous surveillance of the
      cardiac rhythm. Between October 1991 and February 1995, 213 patients implanted
      with a Chorus 6234 or 7034 (Ela Medical) pacemaker, functioning in the DDD (R)
      mode, were followed up using the implanted continuous Holter function. Of the
      patients with no documented supraventricular arrhythmia (SVA) before implantation
      (n = 154), 67 (43.5%) developed SVA during an average period of one year. Male
      patients (p = 0.01; OR = 7.5 on multivariate analysis), high degrees of AVB (p =
      0.03) and the presence of isolated or bursts of atrial extrasystoles (p = 0.004)
      were independent risk factors for SVA. The average time to detection of SVA was
      207 days. In patients with documented SVA before implantation (n = 59), 22
      (37.3%) had no recurrence during follow-up; in the other 37 cases, the average
      period before recurrence was 127 days. Multivariate analysis did not reveal any
      independent risk factor for recurrence of the arrhythmias. On the other hand,
      persistent but delayed atrioventricular conduction (1 degree AVB, long H-V
      interval or bifascicular block), seemed to protect against SVA, independently of
      other variables and of antiarrhythmic therapy (p = 0.008). These results suggest
      a high prevalence of SVA in patients on long-term pacemaker therapy, most
      episodes being asymptomatic. The implanted Holter function would therefore seem
      to be an essential tool for investigating and following up the natural history of
      arrhythmias in these patients.

PMID- 8869250
TI  - [Symptomatic myocardial bridges. Apropos of 6 cases].
AB  - Myocardial bridge is often considered to be a simple anatomical variation often
      observed during coronary angiography. The responsibility of this condition for
      myocardial ischaemia is however uncommon and the physiopathological mechanisms
      are not well understood. The authors report 6 cases of myocardial bridge
      associated with myocardial infarction of unstable angina. The main features of
      this condition are discussed with respect to a review of the literature. Patients
      are usually young and male; the left anterior descending artery is the most
      commonly affected vessel: factors triggering ischaemia are discussed: coronary
      spasm, tachycardia and thrombosis at the site of the myocardial bridge. The
      diagnosis can only be made by coronary angiography showing reduction of the
      systolic diameter of the artery which may be accentuated by certain
      pharmacological tests such as injection of glyceryl trinitrate as used in the
      series.

PMID- 8869251
TI  - [Effects of an anti-c-myb antisense oligonucleotide on myo-intimal proliferation.
      Specificity of action and consequences on vasoreactivity].
AB  - Several reports have shown that an 18-mere antisense oligonucleotide directed
      against c-myb (AS 18) inhibits the proliferation of smooth muscle. The aims of
      this study were to confirm the specificity of a new anti-c-myb antisense and to
      evaluate changes in vasoreactivity following treatment with a c-myb antisense.
      Five groups of rats. All underwent desendothelialisation of the abdominal aorta.
      A solution containing pluronic gel, or one of the following oligonucleotides: AS
      18, 15 mere antisense directed against c-myb, an aleatory 4G sequence containing
      4 consecutive guanosines, a 15 mere antisense mismatch (n = 11), was applied
      around the aorta. After 21 days, the thickness and mean surface areas of the
      media and intima were calculated. Four groups of rats were constituted for the
      vasoreactivity study: control (A), desendothelialisation (B),
      desendothelialisation + application of AS 18 (C) and application of AS 18 alone
      (D). One ring per aorta was sampled at the 21st day and analysed in an organ
      chamber. The following results were obtained: the thickness and average surface
      areas of the intima were smaller (p < 0.05) in the 4G and AS 18-groups; in group
      B, none of the 8 segments responded to acetylcholine; in group C, 6 out of 8
      segments responded. The contraction study showed no differences between groups A
      and D or between groups B and C. The authors conclude that the mode of action of
      AS 18 antisense of c-myb is non-specific but due to the presence of 4 consecutive
      guanosines in the oligonucleotide. Oligonucleotide with this sequence inhibits
      myo-intimal hyperplasia and improves endothelium-dependent relaxation in this
      model without affecting the contraction.

PMID- 8869252
TI  - [Idiopathic monomorphic ventricular tachycardia].
AB  - Idiopathic monomorphic ventricular tachycardia (IVT) represents 10% of all cases
      of VT and is usually observed in young subjects. The origin of the VT may be
      right ventricular, especially in the infundibulum, giving rise to runs of VT with
      inter-critical ventricular extrasystoles of the same morphology, or to paroxysmal
      sustained exercise-induced VT; they usually show left bundle branch block with
      right axis deviation: the triggering mechanism is probably a parasystole
      incompletely protected from the sinus rhythm (for the runs of VT) whereas the
      mechanism of maintenance is probably that of triggered repetitive activity (for
      the runs and paroxysmal forms of VT). When the origin is in the left ventricle,
      the VT shows right bundle branch block and left axis deviation and is typically
      paroxysmal and sustained, triggered by coupled atrial stimulation and followed by
      a post-tachycardial syndrome; these forms are probably due to reentry into or
      near to the left posterior hemibranch. These forms of IVT are unique by: 1) their
      triggering by acceleration of the heart rate, especially during the day, on
      effort or during an emotion; 2) the usual absence of late ventricular potentials
      on surface recordings; 3) their capricious outcome, usually good with 92%
      survival at 10 years; 4) their response to drugs (verapamil, betablockers and/or
      adenosine) which are relatively ineffective against other forms of VT; 5) their
      tendency to recur often leading to radiofrequency ablation procedures (80%
      success rate). The exclusion of underlying inapparent cardiac disease (especially
      arrhythmogenic right ventricular dysplasia) is an essential part of diagnosis.

PMID- 8869253
TI  - [Penetrating atheromatous ulcer of the thoracic aorta. Apropos of a case].
AB  - The authors report a case of penetrating atheromatous ulceration of the
      descending thoracic aorta complicated by a haemothorax. Atheromatous ulceration
      of the aorta is usually observed in elderly hypertensives. It is caused by
      rupture of the internal elastic layer under an atheromatous plaque extending into
      the media and resulting in a parietal haematoma of the aorta. Clinically, the
      differential diagnosis is that of a dissection of the aorta or of fissuration of
      an atheromatous aneurysm. Nowadays, the investigations of choice are a chest CT
      scan with injection of contrast and MRI. Transoesophageal echocardiography
      excludes dissection of the aorta but may miss a direct image of penetrating ulcer
      when the latter is of small size. The treatment of choice is not established
      because the natural history of the condition is not well known. Penetrating ulcer
      would seem to progress slowly to development of an aortic aneurysm. Surgery is
      mainly reserved for forms complicated by painful recurrences or rupture and for
      cases involving the ascending aorta.

PMID- 8869255
TI  - [Endomyocardial fibrosis of the right heart in Behcet disease].
AB  - Cardiac involvement is rare in Behcet's disease. Endomyocardial fibrosis of the
      right heart is exceptionally rare and is associated with right ventricular
      thrombosis. The authors report the case of a 27 year old man who died of a
      massive pulmonary embolism and who suffered from right-sided endomyocardial
      fibrosis with intraventricular thrombi. The diagnosis was made at autopsy.
      Behcet's disease was diagnosed on the finding of bipolar aphthous ulcers and skin
      hypersensitivity. The authors support previous workers in stating that Behcet's
      disease should be considered as a possible cause of endomyocardial fibrosis of
      the right heart.

PMID- 8869254
TI  - [Pure epicarditis after surgical repair of atrial septal defect: a rare form of
      constrictive pericarditis. Apropos of a case].
AB  - The authors report a case of constrictive pericarditis occurring two years after
      surgical repair of an atrial septal defect in a 37 year-old-man. The diagnosis
      was made by right heart catheterisation and magnetic resonance imaging. The
      special feature of this clinical case was the exclusive localisation of the
      fibrosis on the visceral pericardium or epicarditis. The outcome was favourable
      after resection of the visceral pericardium respecting the parietal pericardium.
      Magnetic resonance imaging and right heart catheterisation performed 6 months
      after surgery were normal. Constrictive pericarditis is a classical complication
      of cardiac surgery but relatively rare after repair of an atrial septal defect.
      Isolated involvement of the visceral pericardium is rare and allows surgical
      correction by exclusive epicardectomy respecting the parietal pericardium.

PMID- 8869256
TI  - [Acute myocarditis caused by toxoplasmosis simulating infarction. Apropos of a
      case].
AB  - Acute myocarditis due to toxoplasmosis infection has been previously reported,
      usually in patients suffering from immuno-depression. Cardiac involvement by
      toxoplasmosis is rare in subjects with a normal immunological status. The authors
      report the case of a 16-year-old patient without immuno-depression with acute
      myocarditis caused by toxoplasmosis simulating myocardial infarction.

PMID- 8869257
TI  - [Duration of antivitamin K treatment in venous thromboembolic disease].

PMID- 8869258
TI  - [Louis Rozensztajn (1939-1995)].

PMID- 8869259
TI  - Na,K-adenosinetriphosphatase: the paradigm of a membrane transport protein.

PMID- 8869260
TI  - The homogeneous effect of calcium ionophore A23187 on potassium loss in human
      foetal red cell populations.
AB  - A "pulse like" increase of cytoplasmic calcium concentration, which is
      proportional to ionophore concentration, is induced in red cells by exposure to
      A23187. Different Ca2+ levels are attained depending on cellular calcium
      buffering power and/or primary active calcium transport activation. We examined
      the effect of A23187 concentration of potassium loss in neonatal (nRC) as well as
      in adult red cells (aRC). The increase in ionophore concentration produced an
      "all- or -none" recruitment in adult cells and a "gradual" one in neonatal red
      cells. The "gradual" response observed in nRC would suggest that the "all or
      none" character of the response is not present in red cells during the foetal
      stages of haematopoiesis.

PMID- 8869261
TI  - The use of poly R-478 as a marker to determine gastric emptying and intestinal
      propulsive motility in suckling rats.
AB  - During our studies on gastrointestinal motility in suckling rats using 51Cr or
      51Cr-EDTA as markers, we noticed that these markers--in contrast to studies in
      adult rats--"adhered" to the gastrointestinal wall of sucklings. We therefore
      decided to test the use of another non-absorbable marker Poly R-478 (an
      acetylated anthrapyridone chromophore linked to an polyamino-ethylene-sodium
      ethylene sulfonate copolymer backbone developed by the Dynapol Corporation (Palo
      Alto, CA). This new method has appeared to be useful.

PMID- 8869262
TI  - Dietary oyster mushroom (Pleurotus ostreatus) accelerates plasma cholesterol
      turnover in hypercholesterolaemic rat.
AB  - The effect of adding 5% powdered oyster mushroom (Pleurotus ostreatus) during 12
      weeks on kinetic parameters of cholesterol metabolism was studied in male rats
      (Wistar, initial body weight 85 g) fed a semisynthetic diet containing 0.3% of
      cholesterol. The plasma cholesterol decay curve (examined for the final 29 days
      of the experiment after a single dose of cholesterol-4-14C) was evaluated by
      mathematical analysis using a two-pool model of plasma cholesterol metabolism.
      The oyster mushroom in the diet reduced the half-times of both exponentials
      resulting in lower calculated values (by 28%) of total entry of cholesterol into
      the body cholesterol pool (absorption+endogenous synthesis) and lower sizes of
      both pools (with slower and faster cholesterol exchange). The rate of cholesterol
      exchange between the pools was enhanced and the rate of total clearance of
      cholesterol from the system (metabolic turnover rate of cholesterol i.e. the rate
      of degradation and excretion of cholesterol from the organism) was enhanced by
      50%. The oyster mushroom diet effectively prevented the progress of
      hypercholesterolaemia (decrease by 38%) and cholesterol accumulation in liver
      (decrease by 25%) that were induced by the cholesterol diet.

PMID- 8869263
TI  - The effects of selenium on the antioxidant defense system in the liver of rats
      exposed to cadmium.
AB  - Total superoxide dismutase (total SOD), copper zinc containing superoxide
      dismutase (CuZn SOD), and manganese superoxide dismutase (Mn SOD), catalase
      (CAT), glutathione peroxidase (GSH-Px), and glutathione-S-transferase (GST)
      activities as well as ascorbic acid (AsA), and vitamin E (vit E) concentrations
      were analysed in the liver of rats exposed to cadmium (15 mg Cd/day/kg), selenium
      (7 micrograms Se/day/kg), and to cadmium+selenium (15 mg Cd + 7 micrograms
      Se/day/kg), and in control animals. Cadmium caused a decrease of total SOD, Mn
      SOD, CAT and GSH-Px but an increase of GST activity in the liver of rats.
      Contrary to cadmium, selenium caused a significant increase of the activity of
      these enzymes except for GSH-Px. By concomitant exposure to both cadmium and
      selenium, the toxic effects of cadmium on the activity of mentioned enzymes we
      abolished. In all exposed groups, the activity of enzyme glutathione-S
      transferase was enhanced, indicating its increased role in prevention of lipid
      peroxidation. Cadmium decreased the concentration of AsA and increased the
      concentration of vitamin E in the liver, while selenium increased the
      concentration of both vitamins. However, by concomitant administration of cadmium
      and selenium, these changes were diminished and tended to reach control values.

PMID- 8869264
TI  - The influence of ascorbic acid on the hepatic cytochrome P-450, and glutathione
      in guinea-pigs exposed to 2,4-dichlorophenol.
AB  - Chlorophenols, mainly used as biocides, are compounds with a wide spectrum of
      toxic effects including teratogenic and carcinogenic actions. In this study, the
      effects of 2,4-dichlorophenol (2,4-DCP) on hepatic microsomal cytochrome P-450,
      NADPH-cytochrome c reductase activity, liver ascorbic acid (AA) and glutathione
      (GSH) content were studied in guinea-pigs with a low (2 mg/day/animal) or a high
      (50 mg/day/animal) ascorbic acid intake. The high AA intake significantly
      increased liver AA and GSH levels. There was a clear-cut correlation between
      liver AA and GSH levels. Administration of 2,4-DCP significantly decreased
      cytochrome P-450 and NADPH-cytochrome c reductase activity in hepatic microsomes
      isolated from guinea-pigs with the low AA intake. Such a reduction was not
      observed in intoxicated guinea-pigs with the high AA intake. The results suggest
      that AA can play a protective role in 2,4-DCP toxicity.

PMID- 8869265
TI  - Distribution of catalase, ribonuclease and superoxide dismutase modified by
      monomethoxy (polyethylene glycol) into rat central lymph and lymphatic nodes.
AB  - The plasma-lymphatic distribution of ribonuclease (RNase), superoxide dismutase
      (SODase), and catalase (CTase) modified by monomethoxy (polyethylene glycol)
      (mPEG) was studied in rats. The lymphatic bioavailability (FL) of individual
      enzymes administered intravenously was determined on the basis of plasmatic and
      lymphatic concentration curves. It was concluded that FL values depend on enzyme
      adduct molecular weight (m.w.). The highest FL value was found in mPEG-RNase (the
      lowest m.w.), medium value in mPEG-SODase (intermediate m.w.), and the lowest one
      in mPEG-CTase (the highest m.w.). The binding of these enzymes in the lymphatic
      tissue of iliac, intestinal, brachial and neck nodes was also proportional to
      their molecular weight. The lymphatic binding was dependent on the node
      localization, higher concentrations being found in the iliac and neck nodes in
      contrast to the other nodes (intestinal, brachial).

PMID- 8869266
TI  - The early response of pineal N-acetyltransferase activity, melatonin and
      catecholamine levels in rats irradiated with gamma rays.
AB  - Male Wistar rats adapted to an artificial light-dark regimen (12 h light: 12 h
      darkness) were whole-body irradiated with a dose of 14.35 Gy of gamma rays.
      Irradiation, sham-irradiation and decapitation 30, 60 and 120 min after the
      exposure were performed between 2000 h and 0100 h in the darkness. The serotonin
      N-acetyltransferase activity (NAT), the concentration of melatonin, dopamine,
      norepinephrine and epinephrine were measured in the pineal gland. The serum
      levels of melatonin and corticosterone were also determined. Ionizing radiation
      did not change the activity of the key enzyme of melatonin synthesis, NAT, but
      decreased the concentration of pineal melatonin. The concentration of pineal
      dopamine and norepinephrine decreased 30 and 120 min after exposure, while the
      concentration of epinephrine was elevated 30 min after irradiation, though later
      it was markedly decreased. The serum melatonin level was not changed, but an
      increase in corticosterone level was observed. In the early period after the
      exposure, a decrease in pineal melatonin occurred, accompanied by a decrease in
      pineal catecholamines. On the contrary, in the phase of developed radiation
      injury the signs of increased melatonin synthesis were observed on days 3 and 4
      after the exposure (Kassayova et al. 1993a). The underlying mechanisms require
      further research.

PMID- 8869267
TI  - The first derivation of the Frank Lead ECG at alterations of pulmonary
      ventilation in young healthy women.
AB  - The Frank orthogonal corrected ECG and its first derivation were recorded in 27
      healthy volunteers (women aged 19-22 years) during normal ventilation at rest
      (control group), after voluntary hyperventilation lasting 75 seconds, and during
      hypoxic-hypercapnic ventilation (through the enlarged dead space) lasting 5 min.
      The projections of the magnitude and direction of the positive and negative QRS
      derivation maxima into the horizontal, frontal, left sagittal planes and their
      spatial distribution were constructed. The magnitude of the positive and negative
      QRS derivation maxima was significantly decreased during hypoxic-hypercapnic
      ventilation. A significant alteration in the direction only arose at the positive
      maximum during hypoxic-hypercapnic ventilation in the frontal plane. The
      intrinsicoid deflection was not significantly altered. The normal values of the
      maxima of the first QRS derivation in young healthy women are given. It is
      supposed that the decrease in amplitude of the maxima of the first QRS derivation
      is caused by slowed propagation of the depolarization wave under hypoxic
      hypercapnic conditions and alteration of the direction of the positive maximum is
      caused by a greater participation of the right ventricle at the origin of the
      resulting QRS vector.

PMID- 8869268
TI  - Potential of 31P magnetic resonance spectroscopy in monitoring the viability of
      human renal grafts stored in Euro-Collins perfusion solution.
AB  - The relative concentrations of inorganic phosphate and phosphomonoesters (PME) of
      18 human cadaveric kidneys stored in Euro-Collins perfusion solution were
      measured by 31P MR spectroscopy. The signals of intracellular inorganic phosphate
      (Pii) and inorganic phosphate contained in the perfusion solution (Pie) were
      separated by the deconvolution technique. The ratio of the signal intensities of
      phosphomonoesters and intracellular inorganic phosphate (PME/Pii) was used as a
      marker of kidney viability and correlated with kidney function after
      transplantation. Separation of the Pii and Pie signals in the measured spectra
      was successful in 72% of kidneys. The results of MR analysis satisfactorily agree
      in 78% with the post-transplant function of kidneys.

PMID- 8869269
TI  - Adenohypophyseal ascorbic acid: influences of oestradiol and methylene blue.
AB  - The ascorbic acid (AA) concentration in anterior pituitary and blood plasma was
      measured by the Roe-Kuether method in control rats and rats treated with
      oestradiol benzoate alone, methylene blue alone and with both oestradiol and
      methylene blue. We have found that methylene blue alone caused a significant drop
      in hypophyseal both AA and plasma AA concentrations. Methylene blue treatment
      prevented the increase in plasma AA concentration in oestradiol benzoate-treated
      rats.

PMID- 8869270
TI  - Experimental models and behavioural tests used in the study of Parkinson's
      disease.
AB  - The present review brings the survey of the most frequently used behavioural
      tests in experimental models of Parkinson's disease (PD). Although there is no
      spontaneous occurrence of parkinsonism in animals, several experimental animal
      models of PD have been developed to achieve the same clinical features in
      animals. The techniques employing neurotoxins in lesioning the nigrostriatal
      dopaminergic (DA) system have a large selectivity and reproducibility. The most
      frequently used neurotoxins are 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine
      (MPTP) and 6-hydroxydopamine (6-OHDA). MPTP-lesioned monkeys mimic best the
      symptomatology of PD in human patients while rats appear to be refractory to
      MPTP. For that reason, 6-OHDA is used to damage the substantia nigra in a rodent
      model. Behavioural tests of animals with nigrostriatal lesion represent valuable
      non-invasive methods for assessing the influence of damaged DA system on
      locomotor activity. The most frequently used experimental model of PD is the drug
      evoked rotation in 6-OHDA unilaterally lesioned rats. This model produces well
      defined and stable behavioural deficits. The rotation test is a useful parameter
      for evaluating imbalances of dopamine in both striata of the hemi-parkinsonian
      rat model. T-maze, treadmill running test or sensorimotor tests are used to
      evaluate spontaneous locomotor activity of lesioned animals. Skilled motor tasks
      measure the influence of dopamine-depleting lesions on complex motor acts.
      Transplantation of DA tissue into the striatum offers a new approach to the
      treatment of PD. Experimental models and behavioural tests are used to evaluate
      the extent of graft-induced recovery of MPTP- or 6-OHDA-lesioned animals.
      Different results obtained after the use of different tests reflect the level of
      graft integration into the host circuitry.

PMID- 8869271
TI  - Potentiation of GABAA receptor in cultured mouse hippocampal cells by brain
      derived peptide mixture cerebrolysin.
AB  - Application of Cerebrolysin (0.1 microgram per 1 ml) by a fast microperfusion
      system induced an inward current of 0.2 to 1 nA in all neurones from newborn
      mouse hippocampi held at -30 mV membrane potential. Cerebrolysin-induced currents
      were reduced by the GABAA antagonist bicuculline (2 microM) by 65%, by the NMDA
      antagonist aminophosphovaleric acid (APV, 10 microM) by 27% and by the non-NMDA
      antagonist cyanonitriquinoxalinedione (CNQX, 10 microM) by 20%. Cerebrolysin
      dialyzed through a 3.6 kD gut did not induce any transmembrane current but
      potentiated the response induced by GABA (10 microM) to 135%. We conclude that,
      in addition to amino acids which activate GABAA, NMDA and non-NMDA receptors,
      Cerebrolysin also contains a peptide which potentiates the GABAA receptor
      response.

PMID- 8869272
TI  - Biochemical and morphological changes in isolated rabbit hearts after prolonged
      hypothermic ischaemia: comparison of two cardioplegic solutions.
AB  - This work evaluates the myocardial protective potential of potassium cardioplegia
      on ischaemically arrested and reperfused hearts by two cardioplegic solutions:
      the University of Wisconsin solution (UW) and the standard crystalloid solution
      of St. Thomas' Hospital (ST). Evaluation of myocardial preservation was based on
      creatine kinase and lactate releases and on high-energy phosphate preservation of
      isolated rabbit hearts after 4 hours' hypothermic ischaemia. A morphometric
      ultrastructural evaluation of mitochondria in cardiomyocytes was also performed.
      The hearts of 24 rabbits were normothermally perfused with oxygenated Krebs
      Henseleit solution for 30 min (Langendroff preparation), and the baseline
      contractile performance and biochemical parameters were evaluated. The hearts
      were then arrested and stored in the cardioplegic solutions (12 UW and 12 ST) at
      4 degrees C for 4 hours. The hearts were then rewarmed and reperfused with
      oxygenated Krebs-Henseleit solution for further 30 min. At the end of
      reperfusion, creatine phosphate and high energy phosphates were higher with UW (p
      < 0.05); creatine kinase release during reperfusion was significantly lower with
      UW both at 15 min (p < 0.01) and at 30 min (p < 0.05). Lactate release during the
      first 15 min of reperfusion was about doubled (p < 0.05) with respect to controls
      in both groups; at 30 min this increase had almost vanished (+8%) with UW but not
      with ST (+30%). Ultrastructural morphometry did not show any significant
      difference at the level of mitochondria between the two treatments. The results
      indicate, for UW, an improved myocardial preservation associated with relative
      retention of high-energy phosphates and higher recovery of mechanical function,
      accelerated metabolic recovery and reduced stress of cell membranes.

PMID- 8869273
TI  - Effects of dexamethasone on pancreatic growth and thyroliberin (TRH) content in
      neonatal rat pancreas.
AB  - Thyrotropin-releasing hormone (TRH) is also present in pancreatic B-cells and its
      role and regulation here remain unclear. The rat pancreas displays a peculiar
      ontogenetic pattern for TRH with a rapid increase after birth up to postnatal day
      3 when TRH peak is reached. In the present study, dexamethasone (DXM) treatment
      (1 microgram/100g BW/day) resulted in an increase of pancreatic weight and
      retardation of the peak of pancreatic TRH concentration by two days. The TRH
      degrading system (either in the 10,000 x g supernatant or in the pellet of
      pancreatic homogenate) was not stimulated by in vivo DXM treatment. In DXM
      treated rats, plasma TSH levels were significantly decreased after postnatal day
      1. Plasma glucose concentration was increased on day 1 (i.e. 24 h after the first
      DXM injection) and decreased to the control level on postnatal day 3. Pancreatic
      insulin levels were decreased on postnatal day 3 compared to the controls. These
      results indicate that DXM affects TRH in the neonatal rat pancreas; this effect
      is probably not mediated through modulation of TRH-degrading activity. The
      stimulation of pancreatic growth after DXM treatment might be related to the
      effect on the TRH system.

PMID- 8869274
TI  - Moderate alcohol consumption and vitamin C status in the guinea-pig and the rat.
AB  - The influence of regular moderate ethanol consumption on the status of vitamin C
      was followed in guinea-pigs and rats. In the guinea-pigs examined, 10-day
      consumption of ethanol (4.5 g per day and kg of body weight), administered in
      drinking water under a vitamin C-deficient diet, caused a greater decrease in the
      tissue concentrations and the body-pool of this vitamin than in the group without
      alcohol. In the rats, on the contrary, the daily consumption of ethanol (6% vol)
      during 10 months resulted in an increase in the body stores of vitamin C,
      especially in the liver, adrenals, kidneys, and lungs. Moreover, the biosynthesis
      of ascorbate from D-glucuronolactone in vitro was more intensive (by 30%) in the
      liver microsomes of alcoholized rats than in those of controls (without alcohol).
      These results indicate that the need of vitamin C during chronic consumption of
      moderate alcohol doses is enhanced. This is due to the participation of ascorbate
      in oxidoreducing processes connected with ethanol metabolism which leads to its
      irreversible destruction. In the rat, this loss is compensated by its enhanced
      biosynthesis, while in the guinea-pig it produces increased demands for its
      exogenous intake. If these are not satisfied, a partial vitamin C deficiency may
      occur, which potentiates the harmful effect of alcohol on the health status.

PMID- 8869275
TI  - Inhibitory effect of hydrocortisone on the blood flow and 45Ca and 3H-proline
      incorporation into bones of female rats.
AB  - We studied the effects of hydrocortisone as a possible regulatory factor of bone
      blood flow and metabolism. Local bone blood flow in the tibia, distal femur,
      lumbar vertebra and some soft tissues (using 85Sr-microspheres), as well as 45Ca
      and 3H-proline incorporation into the tibia, bone density and ash weight per ml
      of the tibia were measured in sham-operated and oophorectomized female rats in
      which the influence of hydrocortisone administration (0.004% diet for 5 weeks)
      was followed. Hydrocortisone markedly lowered 85Sr-microsphere uptake and blood
      flow through the bones of non-castrated female rats as well as elevated
      circulatory values in oophorectomized rats. The changes were nearly identical in
      the three bone samples measured; among the soft tissues only the kidneys showed a
      less pronounced decrease. Circulatory changes in the bones seem to be caused by
      local vascular reactions. Hydrocortisone also lowered the 24-hour incorporation
      of 45Ca and 3H-proline into the tibia of both non-castrated and oophorectomized
      females. In the tibia of oophorectomized rats, hydrocortisone normalized the
      decreased bone density and ash weight. The adrenocortical hormones are known to
      block eicosanoid synthesis by the inhibition of arachidonic acid production. It
      is possible, therefore, that local circulatory changes in the bones of rats,
      induced by hydrocortisone, are mediated by the changes in prostaglandin
      production.

PMID- 8869276
TI  - Role of calcium in luteinization stimulator-enhanced progesterone production of
      porcine granulosa cells.
AB  - Intrafollicular luteinization stimulator was shown to be secreted by granulosa
      cells in culture with stimulatory effects on differentiation of immature
      granulosa cells. The purpose of this study was to evaluate the role of calcium
      ions in luteinization stimulator-enhanced luteinization process of granulosa
      cells. We examined the direct effect of ionophore A23187, voltage-sensitive
      Ca(2+)-channel blockers verapamil, nimodipine, nifedipine, niludipine and
      calmodulin antagonist trifluoroperazine on progesterone and cGMP levels in 3-day
      culture of small granulosa cells. It was shown that the dihydropyridine derivates
      of calcium blocker drugs (nimodipine, nifedipine, niludipine) and calmodulin
      antagonist (trifluoroperazine) in the micromolar range, significantly suppressed
      FSH-induced progesterone synthesis and cGMP accumulation in granulosa cells. On
      the contrary, phenylalkylamine calcium blocker verapamil and calcium ionophore
      A23187 had different effects on both processes. Calcium ionophore A23187 markedly
      enhanced cGMP formation, but simultaneously inhibited the FSH-induced
      progesterone synthesis. Verapamil at lower concentrations (10 microM) stimulated
      and at higher concentrations (50 microM) inhibited the formation of cGMP. To
      evaluate the role of extra- and intracellular calcium in luteinization stimulator
      enhanced progesterone production by small granulosa cells, the effects of
      indicative agents on stimulatory activity of follicular fluid from large
      follicles, granulosa cells-conditioned media and granulosa cell extracts were
      tested. While verapamil is shown to be a less potent modulator, administration of
      other calcium antagonists as well as ionophore A23187 caused a significant
      decrease in stimulatory action of follicular fluid from large follicles,
      granulosa cells-conditioned media and extracts. These findings indicate that the
      stimulatory action of luteinization stimulator depends on the transport of
      calcium ions through voltage-sensitive calcium channels and is modulated by
      alteration of intracellular calcium levels.

PMID- 8869277
TI  - Nucleoli and argyrophil nucleolus organizer regions (AgNORs) of cells of the
      megakaryocytic line in the rat.
AB  - The main maturation stages of Norway rat megakaryocytic series, megakaryoblasts
      and mature megakaryocytes, stained by silver for demonstration of argyrophil
      nucleolus organizer regions (AgNORs) were investigated to provide basic
      information on the number of nucleoli and interphasic AgNORs in these cells. The
      results showed that megakaryoblasts as well as mature megakaryocytes possess
      numerous nucleoli; their number and also the number of AgNORs is significantly
      higher in less mature than in more mature cells. The number of AgNORs in
      megakaryocytes of the Norway rat and man are virtually the same, although the
      numbers of nucleolar organizers per haploid chromosome set differ markedly. This
      fact leads to the conclusion that the number of interphasic AgNORs depends on the
      function and metabolic state of the cell rather than on the number of nucleolar
      organizers.

PMID- 8869278
TI  - Comparison of different algorithms for evaluation of respiratory sinus arrhytmia:
      cross-correlation function histogram analysis and regression analysis.
AB  - Three algorithms for assessment of respiratory sinus arrhythmia (RSA) have been
      evaluated: cross-correlation function, histogram analysis and regression plot.
      The algorithms were tested experimentally in a group of 11 subjects. A cross
      correlation function with a high time resolution (1 ms) was used for
      investigation of the time lag between instantaneous heart rate and respiration
      (CTL). This time lag was not affected by the breathing rate in a range of 8 to 29
      breaths per minute. A mathematical model of CTL compared with experimental
      results indicates that respiratory sinus arrhythmia is probably modulated
      directly by the respiratory network in the brainstem rather than by a baroreflex
      in the range of breathing rate investigated. Histogram analysis reflects the
      impact of inspiration and expiration on respiratory sinus arrhythmia. For this
      purpose heart rate changes were separated into two distributions (inspiration
      expiration). The result value (U-VAL) of the Mann-Whitney U-test reflects the
      impact of respiration on heart rate variability. Regression analysis of heart
      rate versus respiration shows that the heart rate increase is more closely
      coupled to inspiration than the heart rate decrease to expiration. Both, CTL and
      U-VAL are thought to be useful parameters for clinical investigation of RSA.

PMID- 8869279
TI  - Muscle NMDA receptors regulate the resting membrane potential through NO
      synthase.
AB  - The early postdenervation depolarization of rat diaphragm muscle fibres (8-10 mV)
      is substantially smaller (3 mV) when muscle strips are bathed with 1 mM L
      glutamate (GLU) or N-methyl-D-aspartate (NMDA). The effects of GLU and NMDA are
      not seen in the presence of aminophosphonovaleric acid (APV), a blocker of NMDA
      subtype of glutamate receptors, 5 mM Mg2+ (which blocks NMDA-controlled ion
      channels) and L-nitroarginine methylester (NAME), an inhibitor of NO-synthase.
      This indicates that NMDA-subtype of GLU receptors might be involved in the
      regulation of the membrane potential in muscle fibres, most probably through the
      NO-synthase system.

PMID- 8869280
TI  - The eosinophil: new insights into its function in human health and disease.

PMID- 8869281
TI  - Cell surface carbohydrates as prognostic markers in human carcinomas.
AB  - Tumour development is usually associated with changes in cell surface
      carbohydrates. These are often divided into changes related to terminal
      carbohydrate structures, which include incomplete synthesis and modification of
      normally existing carbohydrates, and changes in the carbohydrate core structure.
      The latter includes chain elongation of both glycolipids and proteins, increased
      branching of carbohydrates in N-linked glycoproteins, and blocked synthesis of
      carbohydrates in O-linked mucin-like glycoproteins. In mature organisms,
      expression of distinct carbohydrates is restricted to specific cell types; within
      a given tissue, variation in expression may be related to cell maturation. Tumour
      associated carbohydrate structures often reflect a certain stage of cellular
      development; most of these moieties are structures normally found in other adult
      or embryonic tissues. There is no unique tumour carbohydrate structure, since
      certain structures which are tumour-related in one organ may be normal
      constituents of other tissues. Tumour-associated carbohydrate changes have been
      used in the diagnosis of human cancers. Recently, however, it has been
      demonstrated that the expression of some carbohydrate structures is associated
      with prognosis. Tn, sialyl-Tn, and T are cell membrane-bound mucin-like
      carbohydrate structures that may be expressed in tumours due to blocked synthesis
      of the core carbohydrate chain of mucin-like structures. Their expression is
      strongly associated with prognosis in certain tumours, but the biological
      relationship between their expression and tumour progression is at present
      unknown. The blood group-related carbohydrate structures Le(x), sialyl-Le(x),
      ABH, and Le(y) are examples of terminal carbohydrate structures which are related
      to tumour prognosis. These structures are of increasing interest since they may
      function as adhesion molecules; adhesion of tumour cells to endothelial cells of
      blood vessels may be mediated by an interaction between sialosyl-Le(x) and E
      selectin and studies indicate that Le(y) is related to cell motility. These
      findings are now the basis for tumour therapeutic experiments.

PMID- 8869282
TI  - Clinico-pathological features and p53 expression in left-sided sporadic
      colorectal cancers with and without microsatellite instability.
AB  - Defects in mismatch repair (MMR) can result in the development of a 'mutator
      phenotype', manifest as an increase in DNA replication errors (RERs). Patients
      with hereditary non-polyposis colorectal cancer (HNPCC) have germline mutations
      in MMR genes. These patients develop carcinomas of the colon and other specific
      sites at a significantly earlier age than patients with sporadic carcinomas. RERs
      are found in the cancers from patients with HNPCC and have been demonstrated in
      10-20 per cent of sporadic colorectal cancers (CRCs). Loss of MMR may simply
      accelerate tumour development, but it is also possible that these tumours follow
      a different carcinogenetic pathway from tumours with intact MMR. In particular,
      it has been suggested that p53 mutations occur less often in RER-positive (RER+)
      sporadic colorectal cancers. In this study, the clinico-pathological features and
      frequency of p53 overexpression in 17 left-sided RER+ CRCs were compared with 35
      left-sided RER- CRCs. No differences were found in the age and tumour stage at
      presentation, mucinous differentiation, or Jass prognostic grouping between these
      two types of CRC. Thirteen out of 17 (76 per cent) RER+ and 19/35 (54 per cent)
      RER- tumours showed overexpression of p53, a non-significant difference (chi 2
      test). Although some previous studies have suggested differences in the clinico
      pathological features and p53 expression of RER+ and RER- right-sided CRCs, our
      results show that these differences do not exist in left-sided cancers.

PMID- 8869283
TI  - Overexpression of the 67-kD laminin receptor correlates with tumour progression
      in human colorectal carcinoma.
AB  - The high affinity 67-kD laminin receptor (67LR) is a cell surface protein whose
      expression is increased in a number of human carcinoma models. To date, 67LR
      expression in colorectal carcinomas has been examined in a small number of cases.
      67LR expression has been immunohistochemically analysed in a large series of
      human colorectal neoplasms, using the MLuC5 monoclonal antibody. The study
      included 59 samples of non-neoplastic mucosa, 45 polyps (11 hyperplastic, 34
      adenomas), 196 carcinomas, and lymph node metastases of 87 carcinomas. Epithelial
      cells of normal mucosa and hyperplastic polyps were negative or showed weak
      positivity in the paranuclear and apical areas of the cytoplasm. In adenomas and
      carcinomas, the staining was stronger, with a membranous or cytoplasmic pattern.
      The expression of 67LR correlated significantly with the progression from normal
      mucosa (22 per cent) to adenoma (44 per cent), carcinoma (61 per cent), and lymph
      node metastasis (75 per cent) (P < 0.0001). Expression of the laminin receptor
      showed a tendency to be more frequently positive in advanced stage (III+IV; 67
      (III+IV; 67 per cent) when compared with early stage (I+II) carcinomas (54 per
      cent). The difference, however, was not statistically significant (P = 0.058). In
      addition, 14 out of 28 (50 per cent) primary carcinomas without 67LR expression
      became positive in lymph node metastases, while most (86 per cent) of the MLuC5
      positive primary carcinomas were also immunoreactive in metastases. In
      conclusion, these results indicate that 67LR is up-regulated in the progression
      of human colorectal carcinomas and may play a role in the local and metastatic
      progression of these tumours.

PMID- 8869284
TI  - Expression of the type 1 tyrosine kinase growth factor receptors EGF receptor, c
      erbB2 and c-erbB3 in bladder cancer.
AB  - Expression of the c-erbB3 protein was determined in transitional cell carcinoma
      of the bladder by immunohistochemistry. Strong membrane staining was observed in
      10 per cent of cases (7/70) and cytoplasmic and membrane overexpression in 20 per
      cent (14/70). Overexpression of the epidermal growth factor (EGF) receptor (36
      per cent, 25/70) and c-erbB2 proteins (9 per cent 6/70) was determined in the
      same series of cases. c-erbB3 overexpression was positively correlated with EGF
      receptor expression (P < 0.025) but appeared to be inversely associated with c
      erbB2 overexpression.

PMID- 8869285
TI  - Differentiation pathways in primary invasive breast carcinoma as suggested by
      intermediate filament and biopathological marker expression.
AB  - The expression of intermediate filament proteins (IFPs) in 65 primary breast
      carcinomas was analysed by a panel of specific antibodies. Results were
      integrated with the oestrogen and progesterone receptor (ER and PGR) status, Ki
      67 marking, and epidermal growth factor receptor (EGFr) expression. Invasive
      breast carcinomas could be divided into three main groups: group 1 revealed
      positivity only for 'simple epithelial' cytokeratins (CKs 7, 8, 18, and 19);
      group 2 also stained with the antibodies K8.12 and 34 beta E12; while group 3
      showed co-expression of CKs 14 and 17, vimentin, and alpha-smooth muscle actin.
      Group 3 consistently comprised tumours with the highest Ki-67 levels, EGFr
      positivity, and ER-PGR negative status. On the other hand, groups 1 and 2 usually
      exhibited a positive hormonal status, lower proliferative activity, and EGFr
      negativity. The results of this study indicate that the determination of IFPs can
      significantly contribute to the identification of groups of patients with
      different biopathological settings and possibly different clinical behaviour.

PMID- 8869286
TI  - C-erb B-2 staining in primary synovial chondromatosis: a comparison with other
      cartilaginous tumours.
AB  - In this study C-erb B-2 immunostaining has been used to highlight distinct
      differences between the cartilage found in primary synovial chondromatosis (n =
      20), normal articular cartilage (n = 10), benign enchondromas (n = 10), and
      chondrosarcomas (n = 10). There was no positive staining in either the normal
      cartilage or the chondromas, but 15 cases of synovial chondromatosis showed at
      least some staining, although in the majority of cases fewer than 50 per cent of
      cells stained positive. There was no correlation between cellularity/pleomorphism
      and the extent or intensity of staining. Five of the chondrosarcomas were
      positive, with more than 50 per cent of cells showing positive staining in three
      of these cases. All positive cases in this series showed a diffuse cytoplasmic
      staining pattern. Despite these results, there was no Ki-67 positive staining in
      synovial chondromatosis, which tends to suggest that the demonstrated expression
      of C-erb B-2 is not related to proliferative activity. The significance of this
      staining remains undetermined.

PMID- 8869287
TI  - Analysis of human articular chondrocyte CD44 isoform expression and function in
      health and disease.
AB  - Interactions between articular chondrocytes and components of the extracellular
      matrix are of potential importance in the normal function of cartilage and in the
      pathophysiology of arthritis. Little is known of the basis of these interactions,
      but cell adhesive molecules such as CD44 are likely to be involved.
      Immunohistology using six well-characterized anti-CD44 monoclonal antibodies
      demonstrated standard CD44 isoform (CD44H) expression by all chondrocytes in
      normal and osteoarthrotic (OA) cartilage but absence of the CD44E variant.
      Polymerase chain reaction (PCR) of reverse transcribed mRNA from monolayer
      cultures of normal and OA chondrocytes using primer sequences which span the
      region containing variably spliced exons produced a predominant band representing
      the standard form of CD44, which lacks the variable exons 6-15 (v1-v10). No
      product was seen at the expected size of the epithelial variant of CD44 (CD44v8
      10). Use of exon-specific primers, however, showed expression of variant exons
      resulting in multiple minor isoforms. Standard CD44 was also shown to be the
      predominantly expressed isoform identified by immunoprecipitation, but human
      articular chondrocytes did not adhere to hyaluronan in vitro. Chondrocyte CD44
      may function as an adhesion receptor for other matrix molecules such as
      fibronectin or collagen.

PMID- 8869288
TI  - High frequency of apoptosis in infantile capillary haemangioma.
AB  - Infantile capillary haemangioma (ICH) is a well-established clinicopathological
      entity which often regresses spontaneously. To elucidate the cause of spontaneous
      involution of ICH, the apoptotic and proliferative activities in seven cases of
      ICH were compared with those in five cases of lobular capillary haemangioma
      (LCH), using formalin-fixed paraffin-embedded tissue sections. The number of
      apoptotic cells detected by the modified in situ end-labelling method was
      significantly higher in ICH than in LCH, while the proliferative activities
      evaluated with mitosis and Ki-67 antigen expression did not differ significantly.
      Lewisy (Ley) antigen, an apoptosis-associated marker, was expressed in all cases
      of ICH but in none of LCH, while labelling for p53 protein and bcl-2 protein was
      almost completely negative in both tumours. These findings clearly demonstrate a
      much higher apoptotic activity in ICH than in LCH and suggest that apoptosis
      might be a cause of the spontaneous involution of ICH.

PMID- 8869289
TI  - Immunocytochemical expression of the 70 kD heat shock protein in ischaemic bowel
      disease.
AB  - Heat shock proteins (HSPs) are a family of polypeptides which are induced in
      response to diverse forms of cell injury including hyperthermia, anoxia, ethanol,
      heavy metals, and others, with a presumably protective function. Among several
      species of HSPs, the 70 kD protein (HSP70) is the most abundant and consistently
      induced in mammalian cells. Anti-HSP70 monoclonal antibody and a standard
      immunocytochemical method were used to study the expression of HSP70 in 28
      surgical specimens of small and large intestines from patients with ischaemic
      bowel disease. Strong immunoreactivity was observed in viable, regenerating cells
      of both the crypt and surface epithelium within or adjacent to the necrotic foci
      in 86 per cent of the ischaemic bowel specimens. Staining was mostly cytoplasmic,
      but focally both cytoplasmic and nuclear. Smooth muscle cells of the muscularis
      mucosae in the ischaemic areas of some cases also showed immunoreactivity. On the
      other hand, HSP70 was not expressed in control specimens of small and large
      intestine or in colonic specimens of Crohn's disease, ulcerative colitis, and
      adenocarcinoma. These findings suggest a possible role of HSP70 in intestinal
      epithelial and smooth muscle cell response to ischaemic injury, especially in the
      recovery phase.

PMID- 8869290
TI  - Adhesion molecules in human crescentic glomerulonephritis.
AB  - The expression of the intercellular adhesion molecule-1 (ICAM-1) and its ligand
      lymphocyte function associated antigen-1 (LFA-1 or alpha L), the vascular cell
      adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1),
      and the cellular receptors for extracellular matrix, alpha 1, alpha 2, alpha 3,
      alpha 5, alpha 6, alpha V, beta 1, and beta 3 integrin subunits, was studied in
      28 patients with crescentic glomerulonephritis (GN) related to several
      mechanisms: four patients with anti-glomerular basement membrane antibodies or
      anti-GBM disease; 16 with immune complex mediated GN; and eight with pauci-immune
      GN, associated with vasculitis in four cases. A three-step immunoperoxidase
      technique was used on sections obtained from frozen renal biopsies. At the
      initial stage of evolution of the lesions, all the cells of the crescents
      expressed the beta 1, beta 3, alpha 1, alpha 3, and alpha V subunits of
      integrins, ICAM-1, and VCAM-1, and some cells expressed the alpha 2, alpha 5,
      alpha 6, and alpha L subunits of integrins along the plasma membrane. At a later
      stage, when the crescents were fibrocellular, alpha 3 and alpha 1 subunit
      expression was polarized, localized mainly in front of the extracellular matrix.
      In fibrotic crescents, the alpha 2, alpha 5, alpha 6, and alpha L chains were no
      longer detected, and VCAM-1 and ICAM-1 expression was decreased. VCAM-1 and ELAM
      1 appeared on endothelial cells of peritubular capillaries in relation to the
      appearance of infiltrating inflammatory cells. The results of this study show
      that several adhesion molecules were expressed on cells forming crescents and
      were modified during crescent evolution; that these molecules were up-regulated
      on endothelial cells in relation to the severity of the inflammatory response;
      and that whatever the mechanism of the glomerulonephritis, adhesion molecule
      expression was identical. It can be postulated that adhesion molecules play a
      role in crescentic glomerulonephritis. Better knowledge of these molecules in
      human glomerulonephritis may open the way to a new therapeutic approach.

PMID- 8869291
TI  - Atubular glomeruli and glomerular cysts--a possible pathway for nephron loss in
      the human kidney?
AB  - Glomerular tufts were removed and scanning electron microscopy was used to study
      the interior of Bowman's capsule, in order to identify atubular glomeruli. Normal
      renal cortex was studied from six kidneys removed for tumour and six renal
      transplants removed for end-stage rejection. Atubular glomeruli occurred in
      normal renal cortex in less than 1 percent of glomeruli, but were more common in
      transplant nephropathy, representing up to 61 percent of glomeruli. Glomerular
      cysts were identified which also lacked a tubular connection. Both atubular
      glomeruli and glomerular cysts contained a contracted glomerular capillary tuft
      and in both, Bowman's capsule was lined mostly by parietal podocytes. It is
      suggested that atubular glomeruli may be precursors of the glomerular cysts. The
      glomerular tuft may produce filtrate which exits the glomerulus via the parietal
      podocytes on Bowman's capsule. In normal human kidney, the formation of atubular
      glomeruli by disconnection from the tubule may represent an alternative pathway
      for the gradual nephron loss that is associated with ageing. This process may be
      amplified in disease: disconnection from the tubule may be an important part of
      irreversible nephron damage in chronic allograft nephropathy.

PMID- 8869292
TI  - Three-dimensional distribution of basement membrane components in dystrophic
      recessive epidermolysis bullosa.
AB  - Absent or defective collagen VII at the dermo-epidermal junction is the hallmark
      of dystrophic recessive epidermolysis bullosa. Little is known of the alterations
      of other collagenous and non-collagenous components of the basement membrane; it
      is likely that their assembly may be disturbed by the lack of collagen VII
      molecules. The spatial relationship of collagen IV and laminin has been studied,
      both in bullous and in non-bullous areas. Skin biopsies from five patients
      affected by severe dystrophic recessive epidermolysis bullosa were rapidly frozen
      and freeze-dried. Collagen IV and laminin were labelled with specific monoclonal
      antibodies and FITC- or TRITC-conjugated secondary antibodies. Sections were
      observed with conventional light/fluorescence microscopy and with confocal laser
      scanning microscopy. Collagen IV and laminin were not co-localized: the former
      displayed a split image, being present at the floor and the roof of the blister,
      while the latter was confined to the roof. Confocal microscopy also allowed three
      dimensional (3D) reconstruction of the dermo-epidermal junction from a series of
      optical sections, with viewing of the reconstructed specimen from a sequence of
      angles. By this procedure, laminin exhibits an irregular, coarsely granular
      distribution, both in affected and in apparently non-affected areas, while
      collagen IV appears as a homogeneous sheet. These results show that freeze-drying
      is the technique of choice for high-resolution immunofluorescence of skin samples
      and suggest that in dystrophic recessive epidermolysis bullosa, a complex
      disruption of the extracellular matrix assembly exists even before blister
      formation, probably due to the lack of collagen VII.

PMID- 8869293
TI  - Role of macrophages in acetaminophen (paracetamol)-induced hepatotoxicity.
AB  - Research into the pathogenesis of acetaminophen (paracetamol)-induced
      hepatotoxicity has concentrated on the generation of toxic metabolites by the
      hepatocytes. It has, however, recently been shown that human macrophages cultured
      with acetaminophen secrete increased quantities of tumour necrosis factor (TNF).
      This study examines whether macrophages have a direct role in acetaminophen
      toxicity, using a mouse model in which it is possible to eliminate more that 99
      per cent of hepatic macrophages by previously injecting liposomes containing
      dichloromethylene disphosphonate (DMDP). Acetaminophen-induced liver damage was
      assessed biochemically and histologically. It was shown that the liver damage
      occurring 0.5, 1, and 2 h after an intraperitoneal injection of acetaminophen was
      significantly less in mice previously injected with liposomes containing DMDP
      than in previously untreated mice, or mice previously injected with empty
      liposomes. By 4 h there was no difference between the groups. We conclude that
      macrophages play an early and probably a direct role in mediating the liver
      damage due to acetaminophen. This is consistent with the role that macrophages
      have been shown to play in the pathogenesis of alcohol-induced liver damage.

PMID- 8869294
TI  - Aminopeptidase a is a constituent of activated pericytes in angiogenesis.
AB  - Monoclonal antibody (MAb) RC38 recognizes a human renal antigen of 160 kD
      recently identified as human aminopeptidase A (APA; EC 3.4.11.7). This ectoenzyme
      is able to hydrolyse selectively N-terminal glutamyl and aspartyl residues from
      oligopeptides. By enzyme histochemistry, APA activity has also been localized in
      the microvessels of all organs in animals and man. The purpose of this study was
      to investigate the distribution of human APA as recognized by MAb RC38 in the
      microvasculature of normal human tissues and pathological conditions associated
      with neovascularization. Unexpectedly, in normal tissues vascular staining with
      MAb RC38 was generally weak and often absent, while in tumours, granulation
      tissue, and chronic synovitis, marked microvascular staining was demonstrated. By
      immuno-electron microscopy, the antigen was found on the cell membrane of
      activated pericytes and their processes in the tumour vasculature. RC38
      expression could not be detected on cultured human endothelial cells or
      pericytes. These observations suggest that pericyte expression of a subtype of
      APA (as recognized by MAb RC38) is markedly enhanced in the vasculature of
      tumours and wound healing tissue as compared with normal resting tissues. This
      provides further evidence of the altered state of pericytes in these conditions.
      Pericyte APA may be involved in the metabolism of biologically active
      oligopeptides during neovascularization, supporting a regulatory role of
      pericytes in this process. In addition, MAb RC38 may be useful as a marker of
      pericyte activation in tissue sections.

PMID- 8869295
TI  - Apolipoprotein E is associated with islet amyloid and other amyloidoses:
      implications for Alzheimer's disease.
AB  - Apolipoprotein E (ApoE) has recently been proposed as an aetiological factor of
      Alzheimer's disease (AD): ApoE is co-localized to amyloid plaques and
      neurofibrillary tangles in the brain and binds to A beta-protein in vitro. An
      association of ApoE epsilon 4 allele with the development of AD has been
      reported. Islet amyloid is formed from islet amyloid polypeptide (IAPP) in
      pancreatic islets of 90 per cent of patients with non-insulin-dependent diabetes
      mellitus (NIDDM) which, like AD, is an age-dependent pathology. The relationship
      of ApoE to islet amyloid and other amyloidoses is largely unknown. In this study,
      ApoE was localized by immunocytochemistry on pancreatic specimens from non
      diabetic man, monkey, and mouse, and on amyloid-containing human tissues from
      pancreas, heart, brain, and intestine. All types of amyloid deposits,
      irrespective of the constituent peptide, site of deposition, or species, showed
      immunoreactivity for ApoE (ApoE-IR). Quantitative morphometry showed that similar
      proportions of islet amyloid were labelled for IAPP and ApoE in monkey islets.
      ApoE-IR was observed in pancreatic islet cells of non-diabetics. These results
      suggest that the association of ApoE with amyloid is non-specific for AD or to
      the component peptide of amyloid fibrils. If ApoE promotes amyloid formation, its
      synthesis in pancreatic islets could be important for the initiation or the
      development of pancreatic amyloid in NIDDM.

PMID- 8869296
TI  - The effect on chick osteoclasts of infection with paramyxoviruses.
AB  - The detection of virus in osteoclasts from Pagetic patients is now well known,
      but it has yet to be shown convincingly that the presence of virus in Pagetic
      osteoclasts influences their behaviour. In this study, osteoclasts from embryonic
      chick tibiae were infected with canine distemper virus or measles virus and
      compared with mock-infected controls. Infection was confirmed using virus
      specific fluorescent antibodies. It was found that virus infection did not alter
      osteoclast morphology or tartrate-resistant acid phosphatase (TRAP) activity.
      Both infected and mock-infected osteoclasts produced resorption pits on bovine
      bone slices; these could be divided into two distinct size classes with a
      computer-based measuring system. Virus infection significantly increased the
      proportion of the larger size class of resorption pit. These results suggest that
      virus infection can increase bone resorption by osteoclasts, lending further
      support to the hypothesis that viruses play a role in Paget's disease of bone.

PMID- 8869297
TI  - Saphenous vein stripping and quality of outcome.

PMID- 8869298
TI  - Conjoined twins.

PMID- 8869299
TI  - Peritoneal defences and peritoneum-associated lymphoid tissue.
AB  - The peritoneum is mainly protected by the innate immune system. This consists of
      mechanical clearance of the peritoneal cavity, activation of complement, and the
      actions of polymorphonuclear neutrophils and macrophages. The specific immune
      system, which is mediated by the activity of lymphocytes, provides a secondary
      amplification system that may be of great importance for patients with
      intraperitoneal sepsis. This review provides an overview of the relevant innate
      immune mechanisms and explores the possible role of peritoneum-associated
      lymphoid tissue.

PMID- 8869300
TI  - Endocrine and paracrine hormones in the promotion, progression and recurrence of
      breast cancer.
AB  - Both normal and neoplastic breast tissues are stimulated by endocrine and
      paracrine hormones. Epidemiological studies have demonstrated the significant
      role that hormones, growth factors and cytokines have in the promotion,
      progression and recurrence of breast cancer. Significant variations in the
      hormonal environment occur based on age, the cyclical changes occurring during
      the menstrual cycle and (mammographically determined) variations in breast
      composition. These variations have a significant influence on rates of local
      recurrence of breast cancer and survival. This review analyses data relevant to
      these issues and suggests means by which operative results may be improved.

PMID- 8869301
TI  - Anal transitional zone and columnar cuff in restorative proctocolectomy.
AB  - The popularity of double stapling the ileal pouch-anal anastomosis probably owes
      more to the technical ease it brings than to histological considerations or
      functional results. It is preservation of a 'columnar cuff' of mucosa, rather
      than the restricted site of the anal transitional zone, that should be the focus
      of research with respect to long-term risk of malignancy and inflammatory
      complications. If cancer is present in colon that has been removed for ulcerative
      colitis, there is a 25 per cent incidence of dysplasia in the columnar cuff in
      the short term. In other circumstances, those who are spared from carcinoma by
      colectomy are likely to have a similar risk of developing dysplastic change in
      the columnar cuff with longer follow-up. Double stapling the pouch-anal
      anastomosis and preserving the anal canal mucosa improves function, but long-term
      surveillance of the columnar cuff is then required, including biopsies.

PMID- 8869302
TI  - Pulmonary function after laparoscopic cholecystectomy in the elderly.
AB  - The results of laparoscopic cholecystectomy in a group of 52 patients older than
      69 years (group 1) were compared with the results of the same operation in a
      group of 338 younger patients (group 2). In group 1, 23 per cent of patients had
      acute cholecystitis and 13 per cent were operated on after an episode of acute
      pancreatitis. In group 2, 8 per cent of patients had acute cholecystitis and 4
      per cent were operated on after acute pancreatitis. Pulmonary function was
      assessed prospectively before operation, 24 h after surgery and on the seventh
      day after operation, in 20 patients in group 1 and 30 in group 2. In group 1
      there was one death (2 per cent); the morbidity rate was 14 per cent and
      conversion to laparotomy was required in 15 per cent. In group 2 there were no
      deaths, the morbidity rate was 11 per cent and the conversion rate 4 per cent. No
      significant differences were found between the two groups in mortality and
      morbidity rates. Preoperative values of forced vital capacity (FVC) and forced
      expiratory volume in 1 s (FEV1) were significantly lower in group 1 than in group
      2 (P < 0.05); the values of FVC, FEV1 and forced expiratory flow at 50 per cent
      24 h after surgery were less depressed in group 1 (P < 0.01) and also recovered
      more quickly in these patients 7 days after operation. Laparoscopic
      cholecystectomy gives excellent results in geriatric patients and can be
      recommended as the treatment of choice for symptomatic cholelithiasis in the
      elderly.

PMID- 8869303
TI  - Cholangiocarcinoma in patients with opisthorchiasis.
AB  - Cholangiocarcinoma is very common in areas endemic for the liver fluke
      Opisthorchis viverrini. Survival after surgical treatment of cholangiocarcinoma
      associated with opisthorchiasis was studied prospectively in 30 patients, all of
      whom resided in an endemic area. The median age was 52 (range 32-69) years and
      twenty-five patients were men. Seven patients had their tumours removed, four
      with concomitant liver resection. Twenty-two patients underwent palliative
      biliary bypass procedures to a segmental duct. Laparotomy with biopsy of
      metastatic lesions was undertaken in one patient with multiple lymph node
      metastases and peritoneal seedlings. No patient received postoperative
      chemotherapy or radiation treatment. Patients were followed for 2 years or until
      death. The 1-year survival rate after tumour resection was 86 per cent and the 2
      year survival rate 43 per cent. After palliative procedures the 1-year survival
      rate was 26 per cent; no patient reached 2 years and the median survival time was
      8 months. Survival after surgical treatment of cholangiocarcinoma in patients
      with opisthorchiasis is broadly similar to that reported for cholangiocarcinoma
      without liver fluke infestation.

PMID- 8869304
TI  - Surgery for left-sided pancreatic cancer.
AB  - A total of 590 exocrine pancreatic cancers of the body or tail of the pancreas,
      operated on between January 1982 and December 1988, were analysed. There were 128
      pancreatic resections (group 1), 164 palliative bypasses (group 2) and 293
      exploratory laparotomies which included 74 splanchnicectomies (group 3). The
      mortality rate was lower in group 1 (9 per cent) than in group 2 (19 per cent) (P
      = 0.012). The mortality rate exceeded 40 per cent in groups 1 and 2 for patients
      aged more than 70 years with pre-existing organ failure. The morbidity rate was
      32 per cent in group 1 and 29 per cent in group 2. Patients with metastases had a
      median survival of 3.4 months, whatever the operative treatment. In the presence
      of lymph node involvement there was no significant difference in survival between
      groups 1 and 2. Patients with no metastases and no lymph node involvement had 1-
      and 3-year survival rates of 38 and 12 per cent respectively after pancreatic
      resection. Only patients with a small tumour (< or = 4 cm), no lymph node
      involvement and no metastases achieved a significantly better survival after
      resection (P = 0.049). Curative resection should be reserved for a small tumour
      confined to the pancreas. Fewer than 10 per cent of patients will be suitable for
      surgery. For the other cases, resection must be considered as a palliative
      procedure without a significant improvement in survival. It seems justified to
      limit palliative surgery to candidates for digestive bypass and to use non
      surgical palliation for the remainder.

PMID- 8869305
TI  - Proinflammatory cytokine release by peripheral blood mononuclear cells from
      patients with acute pancreatitis.
AB  - Proinflammatory cytokine release was measured from peripheral blood mononuclear
      cells (PBMCs) isolated from six volunteers and, on admission, from 16 patients
      with acute pancreatitis. Tumour necrosis factor (TNF) release in patients did not
      differ significantly from that of volunteers, whereas both interleukin (IL) 6 and
      IL-8 release in patients was raised when compared with that in the volunteer
      group (mean(s.e.m.) IL-6 20.7(4.6) versus 9.3(1.7) ng/ml, P = 0.03; IL-8 283(40)
      versus 128(22) ng/ml, P = 0.04). When variation in white cell count was accounted
      for, IL-6 and IL-8 release but not that of TNF was significantly greater in
      patients with severe disease than in those with mild disease. These results point
      to a complex upregulation of proinflammatory cytokine release from PBMCs in
      patients with acute pancreatitis, components of which relate to the clinical
      progress of the disease.

PMID- 8869306
TI  - Complete resection of the caudate lobe of the liver: technique and results.
AB  - The caudate lobe of the liver is a frequent site of involvement by metastatic or
      primary liver tumours. This study describes the surgical anatomy and analyses the
      operative technique, results and postoperative morbidity of complete caudate
      lobectomy. The data represent a retrospective review of 21 consecutive complete
      caudate lobe resections performed over a 30-month period. The most common
      diagnosis was metastatic colorectal cancer (nine patients) and the most common
      procedure was extended left hepatic lobectomy with en bloc caudate lobectomy.
      Four patients underwent isolated complete caudate lobe resection. The median
      operating time was 5 h and the median blood loss was 1160 ml. The major
      complication rate was 38 per cent (nine major complications in eight patients)
      with 10 per cent mortality rate (two deaths). The median hospital stay was 11
      days. This series demonstrates the feasibility of routine complete caudate lobe
      resection for tumours with general principles of liver resection. Isolated
      caudate lobectomy can be performed safely and the addition of caudate lobectomy
      to major liver resection does not add significantly to the morbidity or mortality
      of the procedure.

PMID- 8869307
TI  - Early measurement of interstitial fibrosis predicts long-term renal function and
      graft survival in renal transplantation.
AB  - This study investigated the relationships between renal allograft interstitial
      fibrosis, renal function and graft survival. A total of 107 consecutive renal
      transplant recipients immunosuppressed with cyclosporin were studied. Needle core
      transplant biopsies were performed before operation and at 1, 6 and 12 months
      after transplantation. Allograft fibrosis was assessed by histomorphometric
      analysis of graft interstitial volume fraction. Renal function was measured by
      isotopic glomerular filtration rate (GFR) measurement at the same time points.
      Interstitial volume fraction was already high in preperfusion biopsies,
      significantly increased with time but stabilized at 6 months after
      transplantation. GFR correlated negatively with interstitial volume fraction at 6
      months (P = 0.05). Interstitial volume fraction at 1 month was not a useful
      predictor of subsequent graft survival but for allografts surviving to 6 months
      an interstitial volume fraction above 25 per cent predicted significantly poorer
      survival (P = 0.04). It provides an objective measure of chronic allograft damage
      and may prove to be a useful surrogate endpoint in the study of therapeutic
      intervention.

PMID- 8869308
TI  - Intra-abdominal Sengstaken-Blakemore tube placement for acute venous outflow
      obstruction in reduced-size liver transplantation.

PMID- 8869309
TI  - Wound metastases following laparoscopic and open surgery for abdominal cancer in
      a rat model.
AB  - The recent application of laparoscopic resection techniques to malignant disease
      has raised safety concerns due to metastasis to surgical access wounds. The
      significance and incidence of this problem are controversial. In the present
      study a rat model, in which an implanted tumour was lacerated, was used to
      investigate whether application of laparoscopic techniques for malignant
      abdominal disease leads to an increased risk of tumour dissemination and
      implantation within the peritoneal cavity, and abdominal wall wounds. Malignant
      cells were implanted into the abdominal wall of 42 rats, resulting 7 days later
      in the growth of a tumour measuring 20-25 mm in diameter. There were three
      control groups: no surgery (n = 6); blunt manipulation of the tumour
      laparoscopically (n = 6); and blunt manipulation of the tumour at laparotomy (n =
      6). Twenty-four rats underwent surgical laceration of the tumour capsule at
      either laparoscopy (n = 12) or laparotomy (n = 12). All rats were killed 1 week
      later, and examined for macroscopic evidence of tumour metastasis. The abdominal
      surgical wounds were excised for independent microscopic examination by a
      histopathologist. Growth of the primary tumour was greater in rats that had an
      operation than in unoperated controls, and was greater after laparotomy. However,
      wound metastases were five times more likely after laparoscopic tumour laceration
      than after the same procedure through an open incision (ten of 12 rats versus two
      of 12, P = 0.0033). Wound metastases following laparoscopic tumour manipulation
      are an important and real problem, with significant implications for the
      application of laparoscopic techniques to excise malignant disease in humans.

PMID- 8869310
TI  - Laparoscopic feeding jejunostomy.

PMID- 8869311
TI  - Prospective study of the aetiology of infusion phlebitis and line failure during
      peripheral parenteral nutrition.
AB  - Four techniques of administering peripheral parenteral nutrition (PPN) were
      examined prospectively to investigate the role of mechanical trauma in the
      development of infusion phlebitis. Patients in group 1 (n = 15) were fed via a
      standard 18-G Teflon cannula which was removed on completion of the infusion and
      was rotated to the contralateral arm every day. Group 2 patients (n = 15) had a
      similar catheter sited in each forearm simultaneously, with rotation of the side
      of infusion each day. Patients in group 3 (n = 17) had a 15-cm Silastic rubber
      catheter inserted into a forearm vein and a standard cannula sited in the
      contralateral forearm, with alternation of infusion each day. Those in group 4 (n
      = 13) had a fine-bore 23-G silicone catheter sited in one arm only. Patients in
      groups 1, 2 and 3 were fed over 12-h cycles and those in group 4 for a 24-h
      continuous cycle. A total of 408 patient-days of PPN were given. Mean duration of
      PPN in groups 1-4 was 7.5, 9, 5.5 and 5 days respectively. Infusion phlebitis was
      not recorded in patients who had a daily change of cannula (group 1), but
      occurred in four patients in group 2, eight in group 3 and eight in group 4.
      Phlebitis scores were 0, 9, 15 and 12 for groups 1-4 respectively. Severe
      phlebitis and line occlusion occurred more frequently in patients with a 15-cm
      catheter (group 3) and in those fed continuously over 24 h (group 4). These
      results suggest that mechanical trauma is an important factor in the aetiology of
      infusion phlebitis. This can be minimized by reducing the time for which the vein
      wall is exposed to nutrient infusion and by reducing the amount of prosthetic
      material within the vein.

PMID- 8869312
TI  - Glyceryl trinitrate prevents neutrophil activation but not thromboxane release
      following ischaemia-reperfusion injury.
AB  - The aim of this study was to determine whether glyceryl trinitrate (GTN) has a
      protective effect on neutrophil-mediated lung injury in a model of aortic
      occlusion (30 min) and reperfusion (120 min). Sprague-Dawley rats were randomized
      into control (n = 11), ischaemia-reperfusion (IR) (n = 12), and IR treated with
      GTN (2 micrograms kg-1 min-1) during reperfusion (n = 10). Myeloperoxidase (MPO)
      activity measured pulmonary neutrophil influx. Pulmonary endothelial permeability
      was measured by wet:dry weight ratio, bronchoalveolar lavage (BAL) protein and
      neutrophil counts. Neutrophil superoxide release was measured by flow cytometry
      in a further IR versus GTN experiment (n = 6 in each group). The significant
      increase in MPO activity produced by IR to a level of 7.99 units g-1 was
      prevented by GTN which reduced the level to 4.73 units g-1. The increase in
      pulmonary microvascular leakage after reperfusion was also prevented by GTN: BAL
      protein without GTN was 992 micrograms ml-1 and with GTN 579 micrograms ml-1; BAL
      neutrophil count without GTN was 3219 cells mm-3 and with GTN 820 cells mm-3; the
      wet:dry lung weight ratio without GTN was 3.8 and with GTN 3.3. Neutrophil
      superoxide release increased significantly after 40 min of reperfusion in the
      untreated IR group (P < 0.05). This increase was prevented in the GTN-treated
      group. GTN administration had no effect on plasma thromboxane production during
      revascularization. These data suggest that GTN administration during the
      reperfusion phase has the potential to decrease pulmonary microvascular injury.

PMID- 8869313
TI  - Preliminary experience with butyl-2-cyanoacrylate adhesive in tension-free
      inguinal hernia repair.

PMID- 8869314
TI  - Vitamin D3 exacerbates intimal hyperplasia in balloon-injured arteries.
AB  - Although a high dose of vitamin D3 is known to cause arterial calcification and
      degeneration, its effect on intimal hyperplasia has never been studied. The aim
      of this study was to examine the influence of a moderate supplement of vitamin D3
      on intimal hyperplasia in the balloon-injured rat carotid artery. Forty-four rats
      had balloon injury to the carotid artery; 22 were given oral vitamin D3
      supplementation (0.25 microgram kg-1 day-1). Animals were killed at 4 weeks and
      the carotid arteries were perfusion fixed and assessed morphometrically by means
      of computerized image analysis of transverse sections. Mean (s.e.m.) intimal area
      was significantly greater in the vitamin D3-treated animals than in controls:
      0.92(0.05) versus 0.71(0.07) mm2 (P = 0.02). The area of the media of both
      injured and uninjured arteries was not influenced by vitamin D3 administration. A
      small dose of vitamin D3 resulted in significant exacerbation of intimal
      hyperplasia in this rat carotid artery model and raises the question of the role
      of dietary vitamin D3 in restenosis following vascular intervention.

PMID- 8869315
TI  - Intraoperative pulse amplitude monitoring of distal perfusion after aortic cross
      clamping.

PMID- 8869316
TI  - Endoscopic subfascial division of incompetent perforating calf veins.

PMID- 8869317
TI  - Carotid endarterectomy without angiography.
AB  - Between 1 January 1990 and 1 September 1994 a total of 109 carotid
      endarterectomies were performed without preoperative angiography. Only two cases
      were considered by the surgeon to have a poor correlation between the duplex
      examination results and intraoperative findings; the outcome was good in both.
      The perioperative mortality rate was 1.8 per cent, one patient dying from sudden
      haematoma causing asphyxia and the other from unrelated causes following a
      myocardial revascularization procedure. Two non-disabling strokes also occurred.
      These results suggest that carotid endarterectomy based on carotid duplex
      scanning alone without preoperative angiography is safe in selected patients.

PMID- 8869318
TI  - Modified technique for double stapling of colorectal anastomosis following low
      anterior resection.

PMID- 8869319
TI  - Sengstaken tube for bleeding rectal angiodysplasia.

PMID- 8869320
TI  - Pathological evidence in support of total mesorectal excision in the management
      of rectal cancer.
AB  - Some 50 total mesorectal excision specimens were examined following rectal
      excision for cancer. Circumferential margin involvement was rare, but mesorectal
      tumour deposits were present in 17 of 44 patients with pT3 tumours, and 23 of 44
      had mesorectal nodal involvement. No patient with a pT2 tumour had mesorectal
      involvement. Failure to excise the mesorectum completely has the potential to
      leave gross or microscopic residual disease that may in theory predispose to
      local failure. Total mesorectal excision is necessary to avoid incomplete
      pathological evaluation of the mesorectum and understaging of rectal cancer.

PMID- 8869321
TI  - Prognosis after surgery in patients with incurable rectal cancer: a population
      based study.
AB  - In a defined population between 1973 and 1992 151 patients with irresectable
      metastatic or local rectal cancer were identified. Eighty-one patients underwent
      resection of the primary tumour (group 1) whereas the primary tumour was left in
      situ in 70 patients (group 2). During the same time period, 444 patients
      underwent curative resection. The median survival was 7.5 months in group 1, and
      3.5 and 1.9 months for surgically and non-surgically treated patients
      respectively in group 2. A colostomy for intestinal obstruction became necessary
      in 12 per cent of the patients with a retained primary tumour. Bilateral hepatic
      involvement, abnormal liver function test results, peritoneal growth or abdominal
      lymph node metastases correlated with a short survival (P < 0.01). These results
      support a selective approach to patients with incurable rectal cancer.

PMID- 8869322
TI  - Risk of extracolonic cancer in familial adenomatous polyposis.

PMID- 8869323
TI  - Prediction of the risk of death by APACHE II scoring in critically ill trauma
      patients without head injury.
AB  - The ability of the Acute Physiology And Chronic Health Evaluation (APACHE) II
      scoring system to predict outcome in 199 critically ill patients with trauma but
      without head injury was assessed prospectively over an 8-month period. Some 178
      patients (89.4 per cent) underwent operation and 50 (25.1 per cent) died, 44
      after operation and six without undergoing surgery. The mean(s.d.) APACHE II
      score was 8.0(5.2) for survivors and 14.5(5.5) for non-survivors (P < 0.001). In
      patients who underwent surgery the mean(s.d.) scores were 7.7(4.6) and 13.4(5.5)
      (P < 0.001) and for those managed without operation 11.1(7.2) and 14.7(6.3) (P =
      0.31) in survivors and non-survivors respectively. The predicted risk of death
      and observed mortality rate were 5.1 and 25.1 per cent respectively for the
      entire group, 5 and 25 per cent for patients undergoing surgery, and 7 and 29 per
      cent for those not operated on. Although the APACHE II system correctly
      identified all survivors (specificity 100 per cent), it failed to predict death
      in any patient (sensitivity 0 per cent). The results suggest that this objective
      prognostic scoring system is not applicable to the patient with trauma who does
      not have concurrent head injury.

PMID- 8869324
TI  - Anatomical basis of intra-arterial chemotherapy for patients with locally
      advanced breast cancer.
AB  - Twenty-eight patients with locally advanced breast cancer received four doses of
      regional chemotherapy via angiographically placed percutaneous catheters into the
      internal mammary artery (IMA) and lateral thoracic artery. Patent blue dye was
      injected to outline the relative contribution to perfusion of each of these
      vessels. The IMA was found to perfuse 67 (range 20-95) per cent of the breast and
      the lateral thoracic artery 15 (range 0-35) per cent. In 33 per cent of patients
      the lateral thoracic artery did not contribute to breast perfusion and a large
      area of the lateral aspect of the breast was perfused from a further branch of
      the subclavian or axillary artery. The blood supply to the breast is extremely
      variable and must be determined in each patient before delivering regional
      chemotherapy.

PMID- 8869325
TI  - Prevention of voice change in singers undergoing thyroidectomy by using a nerve
      stimulator to identify the external laryngeal nerve.

PMID- 8869326
TI  - Bilateral recurrent phaeochromocytoma associated with a growth hormone-secreting
      pituitary tumour.

PMID- 8869328
TI  - Effect of injection of triamcinolone on type 1 procollagen and fibronectin in
      scar tissue.

PMID- 8869327
TI  - Coagulation and fibrinolytic responses of human peritoneal fluid and plasma to
      bacterial peritonitis.
AB  - Significantly higher (P < 0.05) thrombin-antithrombin III complex levels were
      found in the abdominal exudate of patients with peritonitis (median 5500 ng/ml)
      than in that of controls (median 89 ng/ml). In patients, peritoneal fluid
      concentrations of tissue and urokinase-type plasminogen activator were increased
      by factors of 65 and 10 respectively (P < 0.05). The concentration of plasminogen
      activator inhibitor (PAI) 1 was increased by a factor of about 800 (median 395
      versus 0.5 ng/ml, P < 0.05). Despite markedly raised concentrations of PAI,
      peritoneal fluid displayed fibrinolytic activity as demonstrated by significantly
      increased (P < 0.05) concentrations of plasmin-alpha 2-antiplasmin complex
      (median 10,952 versus 57 ng/ml) and fibrin degradation products (median 40,360
      versus 126 ng/ml). There was no correlation between plasma and peritoneal fluid
      concentrations. Intraabdominal coagulation and fibrinolysis are stimulated in the
      abdominal cavity of patients with bacterial peritonitis.

PMID- 8869329
TI  - Food intake after gastrectomy for gastric carcinoma: the role of a gastric
      reservoir.
AB  - Patients with carcinoma of the stomach who underwent curative resection were
      randomized to total gastrectomy (n = 49), total gastrectomy and an S-shaped
      gastric substitute (n = 28) or subtotal gastrectomy (n = 12); all had a Roux-en-Y
      reconstruction. The gastric substitute and gastric remnant allowed a volume of
      400-500 ml to be installed without increments in basal pressures. The
      corresponding volume in the Roux limb was 100 ml. Energy intake was approximately
      120 kJ/kg preoperative weight per day 3 months after operation, and then remained
      constant. Patients who had subtotal gastrectomy ate less (91.7 kJ/kg preoperative
      weight) 3 months after operation, but thereafter increased their intake. Patients
      allocated to have a gastric pouch or subtotal gastrectomy complained more
      frequently of adverse postprandial symptoms (P < 0.03) as a major cause of
      reduced calorie intake. The construction of a gastric reservoir did not improve
      nutritional adaptation after surgery for gastric carcinoma.

PMID- 8869330
TI  - Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and
      pN1 lymph node metastases.
AB  - A retrospective immunohistological analysis of 100 patients with pT1-3 N0 and pT1
      3 N1 gastric adenocarcinoma demonstrated a high frequency of micro-involvement in
      the removed lymph nodes. The presence of three or more tumour cells in more than
      10 per cent of the lymph nodes was of significant prognostic value in the pN0
      cases. Multivariate analysis identified micro-involvement as an independent
      prognostic factor. The results explain why patients benefit from lymphadenectomy
      even if the removed lymph nodes are not involved by tumour (pN0) in routine
      histological examination. The frequent occurrence of micro-involvement is a
      strong argument favouring routine D2 lymph node dissection in gastric cancer
      surgery in patients with lymph node metastasis.

PMID- 8869331
TI  - Prognostic value of monolayer culture patterning in primary cell culture of
      oesophageal cancer.
AB  - The growth of primary cell cultures of oesophageal cancer was compared with the
      clinical outcome of patients from whom the cancers were taken. Ninety-three
      patients underwent curative resection, with no operative deaths, and were divided
      into three groups according to the monolayer culture pattern of the primary cell
      culture: culture from 43 patients (46 per cent) grew no malignant cells (group
      1), 21 (23 per cent) produced monolayer epithelial growth (group 2) and the rest
      (from 29 patients) established cell lines (group 3). The 5-year survival rate of
      patients in group 2 (29 per cent) and group 3 (23 per cent) was significantly
      lower (P < 0.005) than that of those in group 1 (51 per cent). Monolayer
      epithelial growth potential is a significant prognostic factor in patients with
      oesophageal cancer.

PMID- 8869332
TI  - Plasminogen activators in oesophageal carcinoma.
AB  - The expression of components of the plasminogen activator system was investigated
      in patients with oesophageal carcinoma. Tumour and normal mucosa were obtained
      from resected oesophageal carcinomas and antigens were measured by enzyme-linked
      immunosorbent assay. Median levels of urokinase plasminogen activator (uPA) and
      the uPA receptor were higher in carcinoma than in matched normal mucosa (squamous
      cell carcinoma: uPA 4.05 versus 0.66 ng antigen per mg protein, uPA receptor 1.95
      versus 0.50 ng/mg, n = 10, P < 0.05; adenocarcinoma: uPA 2.16 versus 0.61 ng/mg,
      uPA receptor 2.01 versus 0.49 ng/mg, n = 8, P < 0.05). Tissue plasminogen
      activator (tPA) level was lower than control values in squamous cell carcinoma
      but not in adenocarcinoma (1.97 versus 4.70 ng/mg, P < 0.05). There was no
      difference in plasminogen activator inhibitor (PAI) 1 level between carcinoma and
      normal mucosa. The PAI-2 level was lower than that in normals in adenocarcinoma
      only (6.0 versus 64.77 ng/mg, P < 0.05). These data support the hypothesis that
      membrane-bound uPA has a role in the breakdown of extracellular matrix in
      invasive oesophageal carcinoma.

PMID- 8869333
TI  - Randomized trial of blunt-tipped versus cutting needles to reduce glove puncture
      during mass closure of the abdomen.
AB  - Eighty-five consecutive patients were randomized to undergo mass closure of the
      abdomen with no. 1 polydioxanone mounted on either a blunt-tipped (n = 46) or
      cutting (n = 39) needle. Gloves were changed before closure and tested for
      perforation afterwards using standard air or water techniques. Fourteen pairs of
      gloves were punctured when using a cutting needle, and three pairs when a blunt
      tipped needle was used. The majority of punctures were to the non-dominant glove.
      The surgeon was aware of the puncture in eight of the 14 instances involving a
      sharp needle and in one of the three involving a blunt-tipped needle. Blunt
      tipped needles, while not eliminating the risk, significantly reduced the
      incidence of surgical glove puncture (P < 0.001, Fisher's exact test). The use of
      cutting needles for abdominal closure should be abandoned.

PMID- 8869334
TI  - Predeposit autologous blood transfusion in a tropical surgical practice.

PMID- 8869335
TI  - Intravenous cholangiography reduces the need for endoscopic retrograde
      cholangiopancreatography before laparoscopic cholecystectomy.

PMID- 8869336
TI  - Phlegmasia caerulea dolens and venous gangrene.

PMID- 8869337
TI  - A better bridge for loop stomas.

PMID- 8869338
TI  - A better bridge for loop stomas.

PMID- 8869339
TI  - Molecular genetic basis of colorectal cancer susceptibility.

PMID- 8869340
TI  - Local recurrence following total mesorectal excision for rectal cancer.

PMID- 8869341
TI  - Changes in HL-60 cell deformability during differentiation induced by DMSO.
AB  - We have investigated changes in cellular deformability during promyelocytic
      leukemic HL-60 cell maturation. HL-60 cells were induced to mature with 1.25%
      dimethyl sulfoxide. Cellular deformability was evaluated by single-cell
      micropipette aspiration at one day, four days and seven days after induction. HL
      60 cells were found to decrease in size and increase in deformability with
      maturation. When tested under the same aspiration pressures (0.5-1.3 kPa),
      cytoplasmic viscosity was found to vary from 210 to 85 Pa.s for cells prior to
      induction; it varied from 85 to 40 Pa.s for cells seven days after induction.
      Further, cytoplasmic viscosity exhibits power-law dependence on shear rate, mu =
      mu c (gamma m/gamma c)-b, where mu is cytoplasmic viscosity, gamma m is mean
      shear rate during cell entry, mu c is the characteristic viscosity at the
      characteristic shear rate, gamma c, and b is a material coefficient. Cells of all
      maturities showed similar dependence on shear rate (b approximately 0.5), but the
      characteristic viscosity decreased with maturation except for Day 1. When gamma c
      was set to 1 s-1, mu c = 236 +/- 5 Pa.s for cells prior to induction, mu c = 239
      +/- 7, 209 +/- 7 and 175 +/- 14 Pa.s for cells on Days 1, 4 and 7 of induction,
      respectively.

PMID- 8869342
TI  - The effect of aging and pressure on the specific hydraulic conductivity of the
      aortic wall.
AB  - We measured the specific hydraulic conductivity (K) of the human and bovine
      aortic wall, two tissues for which K has not been previously reported in the
      literature, and examined the effects of aging (human) and development (bovine) on
      K. As part of the study, we also examined the effects of mounting the tissue in a
      flat or cylindrical configuration and the effects of perfusion pressure. With
      aging, in the human, we found a modest increase of K with age in a flat geometry;
      this trend was not apparent in a limited number of measurements in a cylindrical
      geometry. No significant dependence of K on developmental stage was found in the
      bovine aortic wall perfused in either a flat or cylindrical geometry. Our results
      indicate that aging and developmental changes of the aortic extracellular matrix
      have minimal effects on its hydrodynamic transport properties as measured.
      Mounting geometry for the aorta has been a concern reported in the literature
      since Yamartino et al. (1974) reported that K in the rabbit was 10-fold lower
      when measured in a flat geometry than in a cylindrical geometry. We found
      mounting geometry to make only a small difference in the calf and the cow, (Kflat
      approximately 2/3 of Kcylindrical), and in the human, we found K to be somewhat
      higher in the flat geometry than in the cylindrical geometry. Higher perfusion
      pressures decreased K of bovine tissue in the flat geometry, but pressure was not
      found to have a significant effect on K in the cylindrical geometry. An
      analytical model demonstrated that the anisotropic nature of the aortic wall
      allows it to be compressible (water-expressing) and yet remain at nearly constant
      tissue volume as the aorta is pressurized in a cylindrical geometry.

PMID- 8869343
TI  - Neutrophil activation in smokers.
AB  - Smoking and elevated leukocyte counts are risk factors for cardiovascular
      disease. Experimental studies suggest that leukocyte activation may be a
      requirement for certain cardiovascular complications. Clinical studies have
      demonstrated activated leukocytes in the peripheral blood of stroke victims.
      Accordingly, neutrophil activation in unseparated whole blood of smokers as well
      as naive neutrophils of non-smokers exposed to plasma of smokers was
      investigated. Both spontaneous superoxide formation as determined by nitroblue
      tetrazolium reduction, as well as pseudopod formation, are significantly elevated
      in autologous neutrophils of smokers. The surface expression of CD18 and L
      selectin on autologous circulating neutrophils of smokers is not significantly
      different from non-smoker controls. In contrast, incubation of naive neutrophils
      with smoker plasma leads to significantly higher levels of superoxide formation,
      pseudopod formation, and L-selectin shedding, compared with non-smoker plasma,
      suggesting that the plasma of smokers contains a transferable factor which causes
      leukocyte activation. The results indicate that analysis of blood samples from
      large peripheral veins may not accurately reflect leukocyte activation in the
      circulation since activated leukocytes have a higher probability to be trapped in
      the microcirculation.

PMID- 8869344
TI  - Optimum kinetic energy dissipation in blood flow in glass capillaries by flow
      field determination: analysis of curvature effect by axial tomographic and image
      velocimetry techniques.
AB  - Based on the variation in the optical density due to erythrocyte concentration
      and movement, the axial tomographic and image velocimetry techniques are
      respectively applied to determine the flow field, i.e., the distribution of
      erythrocytes and axial and radial velocity components, in steady blood flow
      through a curved glass capillary with a diameter of 180 microns. The data at four
      positions (two straight and two curved segments of the capillary) are recorded by
      a video-microscopic system on a video cassette. The erythrocyte and velocity
      distribution profiles change from symmetric at the straight position to an
      asymmetric shape at the curved sections. These profiles become symmetric again at
      the straight section of the capillary. The increase in the radial velocity
      component at curved portions is attributed to the secondary flow. The tomograms
      obtained by concentration profiles show respective changes in the cellular
      population at various cross-sectional positions. The kinetic energy dissipation,
      as calculated based on a determination of the flow field, is the minimum for the
      observed profiles. Any deviation towards parabolic form leads to the dissipation
      of a higher amount of energy.

PMID- 8869345
TI  - Particulate air pollution.

PMID- 8869347
TI  - 18F-fluorodeoxyglucose PET scans in lung cancer.

PMID- 8869346
TI  - Asbestos exposure, asbestosis, and asbestos-attributable lung cancer.

PMID- 8869348
TI  - Video assisted thoracic surgery for spontaneous pneumothorax.

PMID- 8869349
TI  - Lung volume reduction surgery in chronic obstructive pulmonary disease.

PMID- 8869350
TI  - Non-invasive ventilation for exacerbations of respiratory failure in chronic
      obstructive pulmonary disease.

PMID- 8869351
TI  - Neurological complications of severe illness and prolonged mechanical
      ventilation.

PMID- 8869352
TI  - Antibiotic resistant Streptococcus pneumoniae.

PMID- 8869353
TI  - A mild variant of cystic fibrosis.

PMID- 8869354
TI  - Atopy, airway responsiveness, and genes.

PMID- 8869355
TI  - Bronchiolitis and asthma in infancy and early childhood.

PMID- 8869356
TI  - The epidemiology of sleep apnoea.

PMID- 8869357
TI  - [Selenium, glutathione peroxidase, peroxides and platelet functions].
AB  - In the last five years, there has been a renewal of interest in the protective
      role of selenium in vascular disorders, inspired by experimental evidence that
      this trace element could modulate leukotriene and prostaglandin synthesis in both
      endothelial cells and platelets. In people living in low-selenium areas, a
      relationship has been established between a decrease in plasma selenium and an
      increase in the risk of coronary disease, atherosclerosis, platelet
      hyperaggregability and synthesis of proaggregant and proinflammatory compounds
      like thromboxane A2 and leukotrienes. Selenium, as an essential part of
      glutathione peroxidase, takes part in the reduction of hydrogen peroxides and
      lipid peroxides. The concentration of these peroxides, in turn, regulates the
      activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing
      the production of eicosanoids and modulating the balance between a proaggregatory
      and antiaggregatory state. Recent evidence shows that selenium, via its action on
      glutathione peroxidase activity, may be primarily responsible for the regulation
      of the endogenous hydroperoxide level. In human platelets, the activity of
      glutathione peroxidase is particularly high and is very sensitive to the
      requirement of selenium. This sensitivity could explain why platelets of selenium
      deficient subjects show increased aggregation, thromboxane B2 production and
      synthesis of the lipoxygenase-derived compounds. In these deficient subjects,
      selenium administration increases platelet glutathione peroxidase activity and
      inhibits platelet hyperaggregation and leukotriene synthesis. These results
      support the hypothesis that selenium supplementation has a positive effect on
      platelet aggregation in selenium-deficient subjects. In France, more than 10% of
      the population is selenium-deficient and long-term supplementation with low doses
      of selenium could have a beneficial effect on the prevention of both thrombosis
      and coronary heart disease in these subjects.

PMID- 8869358
TI  - [Apoptosis and human viral infections].
AB  - Homeostasis of cell numbers in tissues is maintained by a critical balance
      between cell proliferation and programmed cell death or apoptosis. Many human
      viruses are able to develop suitable strategies for modifying apoptosis in virus
      infected cells and in virus-primed T cells. Apoptosis is characterized by the
      fragmentation of nuclear DNA into 180-200 bp apoptotic bodies and can be analysed
      microscopically or by flow cytometry using staining with various dyes. Moreover
      DNA cleavage can be identified by electrophoresis and by specific labeling using
      in situ nucleotidyltransferase assay (ISNT), terminal deoxynucleotidyltransferase
      mediated dUTP nick-end labeling technique (Tunel), or by Elisa. Adenovirus E1A
      induces expression of protooncogenes c-myc and c-fos which sensitize cells to
      apoptosis; EBV EBNA-5, and adenovirus E1A, HPV E7, and polyomavirus large T act
      in the same way by displacing pRB-bound E2F. EBV EBNA-5, HPV E6, Adenovirus E1B
      55 kDa inactivate the tumor suppressor protein p53 and engage the cells in the
      transformation process. EBV LMP-1, HHV6, and HTLV1 tax induce the antiapoptotic
      bcl-2 protein. EBV BHRF1 encodes proteins with homology to bcl-2 and Adenovirus
      E1B 19 kDa encodes proteins that have protective functions similar to bcl-2.
      Activated lymphocytes responding to viral infections express high levels of fas
      and are susceptible to apoptosis. TNF alpha can down- or up-regulate fas and down
      regulates TNF-R. Adenovirus E1B 19 kDa blocks the proapoptotic activity of TNF
      alpha. Inversly, Cytomegalovirus, hepatitis C virus and Myxoviruses up-regulate
      fas antigen prior to undergoing apoptosis. In HIV-infected patients, CD4+ T-cell
      apoptosis is mediated by the cytopathic effect of the virus and the cell surface
      expression of gp 120-env protein. Moreover, an accelerated T-cell apoptosis in
      HIV-infected individuals is characterized by (i) HIV gp120-CD4+ cross-linking and
      subsequent aberrant signaling of T-cells, (ii) involvement of TNF alpha-fas/Apo-1
      (TNF-R) binding, (iii) involvement of accessory cells as an apoptosis inducer and
      as a result of defective antigen presentation, (iv) possible superantigen
      activity induced by HIV products and cofactors. Many viruses also encode proteins
      with protease activity which could induce apoptosis. The induction of apoptosis
      may result in virus clearance, in contrast the inhibition of apoptosis may result
      in virus cell transformation and viral persistence. Indirectly, the apoptosis of
      infected cells may be induced by CTLs, NK cells and cytokines. In addition,
      apoptosis-mediated physiological depletion of T lymphocytes in the course of
      viral infection can silence the immune response and can induce immunodeficiency.

PMID- 8869359
TI  - [Adaptation of the measurement of plasma and erythrocyte glutathione peroxidase
      activity on Hitachi 911].
AB  - The aim was to automate the assay of plasma and erythrocyte glutathione
      peroxidase (GSH-Px) activity using the Hitachi 911 (Boehringer Mannheim). There
      is a need for a reliable and rapid technique for the determination of GSH-Px
      activity to evaluate 'the oxidative stress'. The technique used was that proposed
      by the Randox laboratories (Randox Laboratories Ltd, Ransel test, reference: RS
      505). The Hitachi 911 was programmed by adapting the manual Randox technique.
      Repeatability, reproducibility and linearity were satisfactory, and usual values
      for plasma and erythrocyte GSH-Px activity were determined. Automation of the
      Ransel test for determination of GSH-Px activity was very useful for serial
      assays. In addition, the technique is practical and has good interlaboratory
      reproducibility.

PMID- 8869360
TI  - [Determination of serum methadone with an immunologic kit and comparison with a
      liquid chromatography method].
AB  - Therapeutic monitoring of patients participating in methadone maintenance
      programmes requires the qualitative or quantitative determination of methadone in
      urine before and during treatment. Generally immunoassay techniques are used for
      this determination, but more and more often measurement of plasma or serum levels
      are required by the physician. The possibility of adapting a commercially
      available FPIA kit (TDX ABBOTT) for urinary assays to the serum determinations
      was investigated. The specific modifications of the method and the dilution
      conditions for high concentrations are described. Results were compared with
      those obtained by liquid chromatography.

PMID- 8869361
TI  - [Determination of Hb A1c in chronic renal failure. Contribution of new
      methodologies].
AB  - Carbamylated haemoglobin arises from the non-enzymatic modification of
      haemoglobin by cyanate derived from spontaneous dissociation of urea. We studied
      the in vitro and in vivo interference of carbamylated haemoglobin in the assay of
      HbA1c by CLHP (ion exchange), affinity chromatography (IMX, Abbott) and
      immunoturbidimetry (Tina-Quant, Boehringer). For patients with chronic renal
      failure on continuous ambulatory peritoneal dialysis, CLHP assay of HbA1c gave an
      error of about +0.35% per 10 mmol/L of urea serum concentration. The IMX and
      especially Tina-Quant assays for measuring HbA1c were not sensitive to cyanate
      interference and constitute interesting alternatives for monitoring glycaemic
      balance in patients with chronic renal failure.

PMID- 8869362
TI  - [Trichophyton soudanense contracted in non-African subjects: apropos of 4 cases
      in France].

PMID- 8869363
TI  - Renal excretion of end products of protein metabolism in urine of endurance
      trained subjects during restriction of muscular activity.
AB  - The objective of this investigation was to determine the rate of renal excretion
      of end products of protein metabolism in urine of 20 endurance trained male
      volunteers aged 23-26 years with an average maximum oxygen uptake of 66 ml.kg
      1.min-1 during 364 days of hypokinesia (decreased number of running steps/day).
      All volunteers were on an average of 10,000 running steps/day prior to their
      exposure to hypokinesia (HK). All volunteers were randomly assigned to one of the
      two groups. Ten volunteers were placed continuously under 13.9 km/day (10,000
      running steps/day) (control subjects) and ten volunteers were subjected
      continuously under 2.7 km/day (3,000 walking steps/day) (hypokinetic subjects).
      During the prehypokinetic period of 60 days and during the hypokinetic period of
      364 days urinary excretion of total nitrogen, urea and creatinine were
      determined. All hypokinetic volunteers displaced significant increases in renal
      excretion of total nitrogen, urea and creatinine as compared to the control group
      of volunteers. It is concluded that prolonged restriction of muscle activity
      induces significant increases in urinary excretion of end products of nitrogen
      metabolism in endurance trained volunteers.

PMID- 8869364
TI  - A new approach in the evaluation of gonadotropins for the diagnosis of polycystic
      ovary syndrome.
AB  - The new immunometric methods using monoclonal antibodies to detect gonadotropins
      revealed a reduction in the absolute values of these hormones, especially LH, due
      to a decrease in cross-reaction between gonadotropin subunits. Therefore,
      reference values of the LH/FSH ratio and their diagnostic significance in the
      polycystic ovary syndrome (PCOS) need to be defined again. We evaluated the LH/
      FSH ratio in basal conditions and after administration of GnRH (100 micrograms as
      i.v. bolus) in seventy patients with PCOS employing an immunoenzymatic method. In
      PCOS patients the LH/FSH ratio was greater than 1 in 70% when evaluated on a
      single sample and in 88% when evaluated on a pooled serum from four samples every
      30 minutes; in the control group the ratio was always lower than 1. The LH/-FSH
      ratio evaluated on the peak values in response to GnRH was greater than 2 in all
      patients and lower than 2 in the control group. Our results indicate that the
      LH/FSH ratio is still an important diagnostic tool in PCOS, especially when
      evaluated on the peak values in response to GnRH, even if its reference values
      are lower using these new monoclonal methods.

PMID- 8869365
TI  - Biliary lithiasis: retrospective analysis of a case series.
AB  - The paper analyses a series of biliary lithiasis cases encountered in 1983-92 in
      which cholelithiasis accounted for 79.3%, cholecystocholedochic calculosis for
      16.6%, chronic stenotic papillitis for 2.1%, residual/recurring calculosis of the
      main biliary way after cholecystectomy for 1.7% and intrahepatic calculosis for
      0.3%. Among the cases involving the main biliary way, the highest percentage
      (35/50 cases or 70%) of transduodenal papillosphincterostomies was performed in
      the first five years, while endoscopic papillosphincterotomy prevailed (28/42 or
      66.7%) in the second five years. The endoscopic technique was initially
      considered elective for residual/recurring biliary calculosis after
      cholecystectomy and for cholecystocholedochic calculosis in patients who were
      elderly and/or at risk. Thereafter its use was gradually extended as
      technological developments allowed its use as a complementary technique in cases
      of giant stones. The advent of minimally invasive surgery has given a further
      boost to the use of endoscopic clean-up procedures in cases of biliary calculosis
      prior to laparoscopic cholecystectomy. The laparoscopic treatment of gallstones
      is a more recent development.

PMID- 8869366
TI  - Ruptured aneurysms of the thoracoabdominal aorta: a case series.
AB  - Fifteen cases of ruptured thoracoabdominal aneurysm (-TAA) were encountered in
      1987-July 1994. These patients included 13 males (86.6%), 2 females (13.4%) with
      a mean age of 66.3 years (range 58-78). Surgery was performed on 13 patients of
      whom 6 (46.1%) died within 30 days. The two other patients had died of heart
      failure prior to surgery. In 8 of these patients (53.4%) the condition was not
      diagnosed until clear symptoms had appeared. The ruptured aneurysms were thoracic
      in 9 cases (60%), abdominal in 6 (40%). The maximum aneurysm diameter in the most
      frequently ruptured group was 6.1-8 cm (in 9 patients-60%)./ For 5 cases (33.4%)
      the maximum diameter of ruptured aneurysms included dorsolumbar pain. In one
      patient a concomitant aortobronchial fistula had produced rupture. Low blood
      pressure was found in 9 cases (60%). In 5 cases (38.4%) curative surgery was
      performed within 24 hours of the onset of symptoms. In this group, the mortality
      rate was 40% (2 patients). In the remaining 8 cases, on whom surgery could not be
      performed within 24 hours (range 25 hours-4 months) the mortality rate was 50% (4
      cases). All four cases of paraplegia (30.7%) were encountered among patients in
      the second group, 2 of whom died. Follow-up revealed a 5-year mortality rate of
      71.4%.

PMID- 8869367
TI  - Effects of ozonized autohaemotherapy on human hair cycle.
AB  - The present paper deals with the effects of ozonized autohaemotherapy on the
      human hair cycle in subjects suffering from androgenetic alopecia. The
      microscopic observation of hairs (trichogram) of 42 subjects (age range = 17-40
      years) was carried out before and after cycles of ozonized autohaemotherapy
      according to the European scientific protocol. The dosage of ozone was 2500-3000
      micrograms for each treatment, one cycle consisting of 16 treatments. Results
      showed a marked improvement of the hair cycle.

PMID- 8869368
TI  - Thrombotic markers during myocardial infarction.
AB  - The authors carried out a study on the behavior of some thrombotic molecular
      "markers" in a group of patients suffering from myocardial infarction, just after
      the first symptoms and after two weeks from the event. The series consists of 12
      subjects (6 males, 6 females, mean age 52 +/- 7), suffering from acute myocardial
      infarction; just after the first symptoms and instrumental signs (before the
      thrombolysis) and after two weeks a venous blood withdrawal was done; on the
      plasma of each sample the determination of fibrinogen (F) (coagulative method),
      tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), D
      dimer (D-D), fibrinopeptide A (FPA) and betathromboglobulin (BTG) (ELISA methods)
      was performed. The values of t-PA, FPA and BTG did not show remarkable
      variations; after two weeks from the myocardial infarction compared to the basal
      values a significant reduction of PAI-1 (4.6 +/- 0.28 UI/ml vs 5.4 +/- 0.33
      UI/ml, p < 0.01), D-D (215 +/- 10 ng/ml, vs 253 +/- 12 ng/ml, p < 0.05) and a
      significant increase of F (294 +/- 28, vs 218 +/- 16 mg%, p < 0.05) were
      observed. The authors suggest that a basal reduction of the fibrinolytic activity
      documented by the enhanced PAI-1, may play a major role, influencing
      pathogenetically the thrombotic event; the other markers seem to be of lower
      importance, being only secondarily altered in the first phase and gradually
      returning to a normal pattern after an adequate elapsed time; a preinfarctual
      hypofibrinolytic condition, probably enhanced by some triggering factor, actually
      appears the sole prothrombotic system to be counteracted with adequate diet and
      drug treatments.

PMID- 8869369
TI  - Food allergy and infantile autism.
AB  - The etiopathogenesis of infantile autism is still unknown. Recently some authors
      have suggested that food peptides might be able to determine toxic effects at the
      level of the central nervous system by interacting with neurotransmitters. In
      fact a worsening of neurological symptoms has been reported in autistic patients
      after the consumption of milk and wheat. The aim of the present study has been to
      verify the efficacy of a cow's milk free diet (or other foods which gave a
      positive result after a skin test) in 36 autistic patients. We also looked for
      immunological signs of food allergy in autistic patients on a free choice diet.
      We noticed a marked improvement in the behavioural symptoms of patients after a
      period of 8 weeks on an elimination diet and we found high levels of IgA antigen
      specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and
      IgM for casein. The levels of these antibodies were significantly higher than
      those of a control group which consisted of 20 healthy children. Our results lead
      us to hypothesise a relationship between food allergy and infantile autism as has
      already been suggested for other disturbances of the central nervous system.

PMID- 8869371
TI  - The diagnosis of so-called "constitutional" bone dysmorphias (embryonal
      osteochondropathies).
AB  - The authors review the diagnosis of so-called "consitutional" bone diseases. They
      criticise the international nomenclature and classification of the latter and
      propose a diagnostic classification for embryonal osteochondropathies, which is
      virtually independent of the structural and metabolic criteria, based on the
      criterion of site and the extent of pathological manifestations. They also
      examine the term "dysmorphia" given that it is the shape of the bone segment
      which first attracts attention and guides the clinical diagnosis of embryonal
      osteochrondropathies.

PMID- 8869370
TI  - Superoxide dismutase and other biochemical disorders in a family with Fanconi's
      anemia.
AB  - Activities of superoxide dismutase, glutathione reductase, pyruvate kinase and
      glucose-6-phosphate dehydrogenase and level of fetal hemoglobin were determined
      in a family with Fanconi's anemia. Superoxide dismutase activity was
      significantly decreased, but glutathione reductase, pyruvate kinase and glucose-6
      phosphate dehydrogenase activities were normal. The fetal hemoglobin levels
      observed were increased when compared with standard levels.

PMID- 8869372
TI  - Facial nerve paralysis following pediatric cardiac surgery.
AB  - A newborn female diagnosed with transposition of the great vessels with
      restrictive ventricular septal defect presented left facial peripheral nerve
      paralysis following anatomical surgery correction (arterial switch) by
      cardiopulmonary bypass. We have not found any causal factor either in the
      anesthesia or postoperative period. The electromyogram presented signs of
      peripheral nerve impairment, and the cerebral echography and electroencephalogram
      were normal. The facial nerve paralysis was almost recovered seven weeks after
      surgery. This is the first pediatric patient reported with peripheral facial
      nerve paralysis after cardiac surgery.

PMID- 8869373
TI  - Ruptured aneurysm of the internal iliac artery.
AB  - The aneurysms of the internal iliac artery are rare and very often asymptomatic.
      Because of the anatomic location of this artery, it can be difficult to diagnose
      this kind of aneurysm, when isolated. Frequently it is diagnosed in consequence
      of aneurysmatic complication, such as rupture and/or impending rupture. In this
      work we report our experience concerning 6 cases of ruptured aneurysm of the
      internal iliac artery, observed in 5 patients. In three of these cases the lesion
      was isolated. In two cases the patients had already been operated on for
      abdominal aortic aneurysm, 4 and 6 years before. All the five patients were
      operated on. In 5 cases we ligated the aneurysm, without using any vascular
      graft. In one case where the external iliac artery was involved, we used a
      vascular graft between the common iliac and common femoral artery, in order to
      repair the vascular axis. One case of mortality was observed and a rare
      complication occurred in one case. An 83-year-old man treated in emergency for
      ruptured aneurysm of the left internal iliac artery, with regular post-operative
      course, was hospitalized again 24 days later with sepsis and pain in the left
      lower abdomen. A CT scan and a following urography showed a urinary fistula
      probably due to an ischemic necrosis of a segment of the ureter. A percutaneous
      nephrostomy has been performed and the patient successfully discharged.

PMID- 8869374
TI  - Ruptured aneurysm of the superficial femoral artery.
AB  - OBJECTIVE: True isolated "arteriosclerotic" aneurysms of the superficial femoral
      artery are rare. One case of isolated superficial femoral artery aneurysm and
      review of literature is reported. DESIGN: Case report and review of the
      literature. SETTING: Hospitalized care. PATIENT: An 80-year old man presenting
      with rupture of superficial femoral artery aneurysm was observed and treated with
      graft interposition, which resulted in limb salvage. INTERVENTION: Removal of the
      aneurysm and replacing of the arterial aneurysmatic segment by interposition of a
      polytetrafluoroethylene prosthetic graft. MEASURES: Patency of the graft with no
      evidence of ischemic or embolic complication assessed with a follow-up period of
      6 months. RESULTS: From the review of the literature we collected 21 isolated
      true arteriosclerotic superficial femoral artery aneurysms in 17 patients. These
      aneurysms may be discovered after the onset of complications such as rupture
      (33%) or thrombosis and limb ischemia (19%). Other aneurysms are frequently
      concomitant (69%), mostly represented by abdominal aortic aneurysms (40%).
      CONCLUSIONS: Ruptured arteriosclerotic aneurysm of the superficial femoral artery
      is very uncommon and the treatment of choice is based on replacing of the
      aneurysmal segment with a prosthetic graft interposition or proximal and distal
      artery ligation and bypass. Early diagnosis and surgical reconstruction is
      recommended for patients with aneurysms of the superficial femoral artery that
      are 2.5 cm or greater in maximum diameter and for complicated aneurysms of any
      size.

PMID- 8869375
TI  - Giant left atrial myxoma: case report.
AB  - This report describes the case of a 40 year old woman with a giant left atrial
      myxoma. Only a thin path of 9 mm diameter allowed blood flow through the left
      atrial chamber to the left ventricle. Despite this obstruction, the patient
      developed only minimal symptoms. Echocardiography, especially transoesophageal
      mode is the diagnostic procedure of choice to detect these tumours. The giant
      mass was successfully removed and the patient is doing well two years after
      surgery.

PMID- 8869376
TI  - The use of the right atrial free wall for reconstruction of the outflow tract in
      a patient with Fallot's tetralogy: a case report.
AB  - We report the use of the lateral wall of the right atrium, as a free graft, for
      the reconstruction of the narrow outflow tract in a patient with Fallot's
      tetralogy. Pericardium was used for closure of the ventricular septal defect,
      widening of the narrow pulmonary trunk and reconstruction of the right atrium.
      Postoperative echocardiographic studies showed cyclic shortening of the
      transplanted atrial tissue, a 40% increase in right ventricular ejection fraction
      and preserved (e) and (a) waves denoting normal blood flow pattern across the
      tricuspid value. Electrophysiological study carried out 6 months postoperatively
      recorded ventricular potential at the site of patch. The application of this
      technique may be considered, ona limited series of patients, for possible
      amelioration of the postoperative right ventricular dysfunction, whenever
      widening of its infundibulum is indicated.

PMID- 8869377
TI  - Malignant melanoma of the vagina in pregnancy: description of a clinical case.
AB  - Vaginal melanoma in pregnancy is a rare but extremely malignant tumour for which
      the prognosis is worsened by the fact that pregnancy increases the secretion of
      Melanocyte-Stimulating Hormone (MSH). The clinical case is described of a
      malignant vaginal melanoma in a 27 year-old woman in her 38th week of gestation,
      who was referred for slight vaginal bleeding. Clinical examination revealed a 3
      cm pedunculate tumour on the anterior wall of the vagina. Vaginal cytology
      suggested a melanoma and instrumental examination failed to reveal any lymph node
      involvement. The vaginal tumour was removed during a caesarean section and
      subsequent histological examination identified it as a Breslow Stage II malignant
      melanoma. A 24-month follow-up showed the patient to have been completely cured.

PMID- 8869378
TI  - Usefulness of frequency analysis of cytotoxic T-lymphocytes precursors (CTL-p)
      for selection of HLA matched unrelated marrow donors.
AB  - A child with Sanfilippo syndrome and 5 potential unrelated marrow donors were
      typed serologically, tested in mixed lymphocyte reaction and typed by restriction
      fragment length polymorphism analysis in attempt to find a suitable donor. All
      donors were found to be identical with the recipient, however, these studies were
      not conclusive in identifying the best match donor. Therefore, recipient-donor
      pairs were examined by HLA-DR oligotyping. In addition we have studied the
      potential of cytotoxic T-lymphocytes precursors (CTL-p) analysis as a means of
      selection for matched unrelated donors. Low frequencies (1/10(5)) of
      pretransplant CTL-p correlated with oligotyping identity in all donor-recipient
      pairs evaluated. In one case oligotyping disclosed a previously unrecognized HLA
      DRB1 disparity. This resulted in high frequencies of CTL-p (1/35,000). Based on
      this experience we can argue that CTL-p analysis may be used as an additional
      tool for selection of compatible unrelated marrow donors.

PMID- 8869379
TI  - Diverse patterns of performance in copying and severity of unilateral spatial
      neglect.
AB  - We analysed the performances of 69 patients with left unilateral spatial neglect
      in copying a multi-object figure, as well as their performance of the line
      cancellation and line bisection tests. Three patterns of copying were mainly
      observed. The first pattern was almost satisfactory performance in copying the
      central figure with occasional omission of the elements located more laterally to
      the left. The second pattern was omission of the left half of the whole figure,
      which was the pattern expected of patients with typical left unilateral spatial
      neglect. The third pattern was left unilateral spatial neglect when copying the
      central figure, with favourable copying of left lateral objects; this may be
      regarded as "object-centered" neglect. Performance of the line cancellation test,
      which requires exploratory ability, was significantly better for the patients
      with the third pattern than for those with the second pattern. A significant
      difference was also observed between the two groups of patients in performance of
      the line bisection test, in which exploratory ability plays a more minor role. No
      significant difference was found in performance of the line cancellation and line
      bisection tests between the patients with the third and first patterns, in spite
      of remarkable differences in their copying performances. No distinctive
      characteristics were found for any group of patients as regards lesion, age,
      duration after onset, education, and WAIS scores. Therefore we concluded that in
      most of our patients with neglect, these diverse patterns of copying deficits
      resulted from different levels of neglect severity but not from different types
      of unilateral spatial neglect.

PMID- 8869380
TI  - Spinal arteriovenous malformations: clinical and neurophysiological findings.
AB  - Eighteen patients with dural arteriovenous fistulas or intradural arteriovenous
      malformations underwent clinical and neurophysiological examination. Bladder
      disturbances, pain, sensory abnormalities and involvement of both upper and lower
      motor neurons were commonly observed. Abnormal findings were obtained both in
      electromyography (11/18) and somatosensory evoked potentials (16/18). The motor
      evoked potentials were abnormal in all but one patient and showed a prolonged
      central (n = 14) or peripheral motor conduction time (n = 6). In three cases both
      values were prolonged. The results of nerve conduction studies in the patients
      with prolonged peripheral motor conduction times were normal. These
      neurophysiological findings may indicate root involvement in some patients,
      probably due to venous congestion and consequent hypoxia, as there were no signs
      of root compression on neuroradiological evaluation in any of these six patients.
      Motor evoked potentials may provide an additional clue to the diagnosis, although
      patients with spinal stenosis or motor neuron disease may present with similar
      findings.

PMID- 8869381
TI  - Low serum interleukin-10 levels in multiple sclerosis: further evidence for
      decreased systemic immunosuppression?
AB  - Serum interleukin 10 (IL10) levels were assessed in patients with multiple
      sclerosis who were either in a stable or active clinical condition. The levels
      were compared with values in healthy controls. Lower IL10 levels than in controls
      were seen in multiple sclerosis patients, regardless of clinical disease
      activity. Low IL10 levels were also seen in patients with systemic lupus
      erythematosus. No clear-cut relationships emerged between IL10 levels and those
      of tumour necrosis factor alpha and transforming growth factor beta, or between
      IL10 and lymphocyte subsets in peripheral blood.

PMID- 8869382
TI  - Postganglionic cholinergic dysautonomia with incomplete recovery: a clinical,
      neurophysiological and immunological case study.
AB  - A 26-year-old man presented with signs and symptoms of marked postganglionic
      cholinergic autonomic dysfunction manifested by non-reacting dilated pupils,
      paresis of accommodation, decreased salivation, dry skin, atony of the bladder,
      erectile impotence and complete gastrointestinal paresis. Standard
      neurophysiological tests for myelinated sensory and motor fibre function and
      quantitative methods to examine unmyelinated parasympathetic, sympathetic and
      afferent fibres were performed: parasympathetic function was measured by heart
      rate variation tests. Sympathetic cutaneous vasoconstrictor responses induced by
      deep inspiration were examined with laser Doppler flowmetry. Cutaneous
      nociceptive C-fibre function was assessed by measurement of axon reflex
      vasodilatation and flare size induced by histamine iontophoresis. The findings
      confirmed that the abnormalities were restricted exclusively to the cholinergic
      postganglionic autonomic systems. All other functions were completely preserved.
      Modern neurophysiological methods of testing sympathetic and afferent small fibre
      function might help in the diagnosis of cholinergic postganglionic dysautonomia
      in the early stages. The specificity of the dysfunction argues in favour of an
      immunological pathogenesis. However, antibody screening including acetylcholine
      receptor antibodies and voltage-gated calcium channel antibodies gave negative
      results. Whatever autoimmunological mechanism might be involved, the postulated
      antibodies act highly specifically on unknown structures of the cholinergic
      postganglionic autonomic neurons.

PMID- 8869383
TI  - Intravenous immunoglobulin treatment in the prevention of childbirth-associated
      acute exacerbations in multiple sclerosis: a pilot study.
AB  - Acute exacerbations frequently occur after childbirth in patients with relapsing
      remitting multiple sclerosis (MS). The present pilot study was initiated in an
      attempt to reduce the number of childbirth-associated acute exacerbations in the
      postpartum period. We treated nine MS patients with a history of 12 childbirth
      associated acute exacerbations that had occurred 2-9 weeks after previous
      deliveries. The patients were administered intravenous immunoglobulin (IVIg) at a
      dose of 0.4 g/kg per day for 5 consecutive days during the 1st week after
      childbirth and at 6 and 12 weeks thereafter. None of the treated patients
      relapsed during the 6-month period after delivery. However, three patients had a
      remote relapse, two at 8 months and one at 10 months after childbirth, but these
      probably represented the natural course of disease and were not associated with
      childbirth. We conclude that IVIg treatment may prevent acute childbirth
      associated exacerbations in relapsing-remitting MS patients.

PMID- 8869384
TI  - Impairment of visuospatial function in idiopathic spasmodic torticollis.
AB  - We studied visuospatial function in 15 patients with idiopathic spasmodic
      torticollis (ST) and 15 age- and sex-matched controls. All subjects underwent a
      battery of visuospatial tests, assessing different functional components of
      spatial ability. The performance of ST patients on tasks of spatial perception
      did not significantly differ from that of normal subjects, but patients performed
      significantly worse on spatial tasks requiring mental manipulation of personal
      space. This distinct pattern of visuospatial impairment may result from basal
      ganglia dysfunction.

PMID- 8869385
TI  - Neuropathy associated with "benign" anti-myelin-associated glycoprotein IgM
      gammopathy: clinical, immunological, neurophysiological pathological findings and
      response to treatment in 33 cases.
AB  - We studied 33 patients presenting with a peripheral neuropathy associated with
      non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy
      (MG) in an attempt to delineate their clinical, immunological,
      electrophysiological and pathological characteristics; we also reviewed our
      experience concerning long-term follow-up and therapy. Peripheral neuropathy
      associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex
      ratio 7.2), and mean age at onset was 67 years (range 46-81). A predominantly
      sensory pattern was noted in more than 80% of cases, although some patients were
      affected by a predominantly motor peripheral neuropathy. Although disease
      progression was slow in most cases, 45% of patients suffered severe disability,
      and in 2 cases, the patient's death appeared to stem directly from the
      neuropathy. The electrophysiological findings were indicative of a demyelinating
      process in 90% of cases, and electron microscopic examination of nerve biopsy
      specimens demonstrated widening of the myelin lamellae in more than 95% of cases.
      Most of our patients showed a disappointing response to steroids and chemotherapy
      or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a
      transient, mostly subjective effect in 35% and led to a clear-cut improvement in
      24% of cases. We did not observe any correlation between the severity of the
      clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in
      individual cases, clinical improvement occurred without lowering of IgM levels.
      Although the severity and the rate of progression may greatly vary from patient
      to patient, the combination of clinical, electrophysiological and pathological
      features delineates a characteristic pattern in peripheral neuropathy associated
      with non-malignant anti-MAG IgM MG.

PMID- 8869386
TI  - Large striatocapsular infarcts: clinical features and risk factors.
AB  - We defined large striatocapsular infarcts as subcortical softenings of more than
      20 mm in diameter involving the territories of the lateral and medial groups of
      lenticulostriate arteries. The aim of this study of 56 patients was to compare
      the clinical features and risk factors of these infarcts with those of cortical
      and lacunar infarcts. On the whole, our data suggest that both the clinical
      features and risk factors of large striatocapsular infarcts are similar to those
      of cortical infarcts, but significantly different from those of lacunar infarcts.
      The clinical manifestations of large striatocapsular infarcts with a maximum
      diameter of less than 50 mm may sometimes resemble those of lacunar infarcts
      because neuropsychological disorders are less frequent; however, our study
      indicates that, even in these cases, cardioembolic sources and artery-to-artery
      embolism are significantly more frequent in large striatocapsular than in lacunar
      infarcts, thus suggesting a different pathogenesis.

PMID- 8869387
TI  - Systemic and anti-neuronal auto-antibodies in patients with paraneoplastic
      neurological disease.
AB  - Sera from 23 patients with paraneoplastic disease of the central nervous system
      (PNS) were examined for the presence of anti-neuronal (anti-Hu, anti-Yo/PCA) and
      anti-Ri) and systemic auto-antibodies, including antibodies against DNA,
      centromeres, nRNP, Sm antigen, Scl-70, Ro(SS-A), La(SS-B), mitochondria, thyroid
      antigens, parietal calls, brush border antigen and rheumatoid factor. As
      controls, sera from 33 patients with small cell lung cancer, 33 with ovarian
      cancer and 7 with breast cancer and from 107 aged-matched healthy persons were
      used. Systemic auto-antibodies were found in 52% of patients with paraneoplastic
      neurological syndromes compared with only 16% (P = 0.001) in the control group
      with cancer only and 15% in the group of healthy controls. The relatively high
      percentage of systemic auto-antibodies in patients with PNS indicates that there
      is a genetic susceptibility to the development of auto-immune phenomena. This may
      provide an explanation for the relatively rare occurrence of PNS in patients with
      cancer.

PMID- 8869388
TI  - Synthesis of anti-acetylcholine receptor antibodies by CD5- B cells from
      peripheral blood of myasthenia gravis patients.
AB  - An increased frequency of CD5+ B cells (or, according to a new nomenclature, B1
      cells) has been detected in the peripheral blood of a proportion of patients with
      myasthenia gravis (MG), as in some other autoimmune diseases. To elucidate the
      pathogenic significance of this B-cell subset in myasthenia gravis, mononuclear
      cells from the peripheral blood of six MG patients were separated into T and B
      lymphocytes by a magnetic cell separation procedure employing superparamagnetic
      microbeads (MACS). Subsequently, the B-cell fraction was depleted of CD5+ B cells
      in a second separation. The resulting purified CD5- B-cell fraction was cultured
      alone or with the addition of autologous T cells. Anti-acetylcholine receptor
      (AChR) synthesis by CD5- B cells in cultures with T cells was significantly
      increased by pokeweed mitogen (176 +/- 130 fmol/ml per week/2 x 10(5) B cells)
      compared with unfractionated cells (75 +/- 101) or CD5- B cells alone (19 +/- 4).
      These results demonstrate that in MG anti-AChR are synthesized, at least in part,
      by CD5- B cells which are dependent on T cells. Although this does not exclude
      the existence of AChR-specific CD5+ B cells, it provides evidence against a
      pivotal role of this B-cell subset in anti-AChR synthesis.

PMID- 8869389
TI  - Ultrastructural immunolabelling of amyloid fibrils in acquired and hereditary
      amyloid neuropathies.
AB  - Both acquired and familial amyloid neuropathies carry a poor prognosis. In
      addition, amyloid is sometimes difficult to visualise in nerve biopsy specimens,
      and the pathogenesis of nerve lesions is still a matter of controversy. In order
      to learn more on the subject, we studied nerve specimens from seven patients with
      proven amyloid neuropathy by ultrastructural immunocytochemistry in order to
      better understand their pathogeny and to evaluate the reliability of the method
      for detection of amyloid antigens in the endoneurium. An indirect immunolabelling
      technique using protein A-gold complex (pA-g) was applied. Polyclonal antisera
      against human IgG, IgM, lambda and kappa light chains and prealbumin were
      assayed. Amyloid fibrils were labelled in six of seven cases: in four cases with
      anti-transthyretin (TTR) antibodies and in two with anti-lambda light chain
      antibodies. The type of immunolabelling correlated with the biochemical type of
      the amyloidosis as defined by TTR gene analysis and serum immunoelectrophoresis.
      The amyloid fibrils and gold labelling were always located in the endoneurial
      space. No intracellular deposit or labelling was found. The immunolabelling was
      highly specific, gold particles being detected only near to amyloid fibrils with
      no background gold labelling. Ultrastructural immunolabelling with pA-g could be
      used for detection of amyloid in progressive axonal neuropathy of unknown origin,
      with important therapeutic implications.

PMID- 8869390
TI  - Double-blind study of the activity and tolerability of cabergoline versus placebo
      in parkinsonians with motor fluctuations.
AB  - The use of a dopamine agonist with a long duration of action has theoretical
      advantages in attempting to reduce the motor fluctuations in Parkinson's disease.
      We report the results of a double-blind controlled study of adding cabergoline,
      an ergot derivative with potent long-lasting high affinity for the D2 receptor,
      to levodopa therapy in 37 patients with severe fluctuations in response to
      treatment. Increasing dosages of cabergoline (19 patients) or placebo (18
      patients) were added to each patient's stable levodopa regime. The two patient
      groups were similar at baseline in terms of age, disease duration, duration of
      levodopa treatment, and average hours "off" per day. Following incremental dose
      titration, patients in the cabergoline group had a significant reduction in hours
      "off" per day from 5.0 (SD 2.1) to 3.0 (SD 2.5), but there was no change in this
      measure in the placebo group [4.0 (2.2) and 3.3 (2.3) respectively]. This was not
      at the expense of a significant increase in dyskinesia. However, there was no
      difference between the groups when comparing their average Hoehn and Yahr stage
      of disease, and Schwab and England activities of daily living index.

PMID- 8869391
TI  - Serial changes in motor and somatosensory evoked potentials in putaminal
      haemorrhage.
AB  - Little is known about evoked potential changes in putaminal haemorrhage. In this
      study, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs)
      have been serially evaluated and their role in the prognosis of putaminal
      haemorrhage is now reported. Nineteen patients with CT- or MRI-proven putaminal
      haemorrhage were examined after a mean duration of 13 days (range 2-30); there
      were 4 females and 9 males, ranging in age between 25 and 70 years. The
      haematomas were of medium size in 13 and large or small in 3 patients each. The
      changes in the clinical picture and the SEPs and MEPs were evaluated on
      admission, and after 30 and 90 days. Central motor conduction time (CMCT) could
      not be recorded in 13, but was prolonged in 2 and normal in 4 patients. Median
      SEPs revealed the absence of near field potentials in 11 and prolongation of N9
      N20 conduction time in 1 patient. In the follow-up period MEP and SEP
      abnormalities only changed in 5 patients; MEPs changed in 4 and SEPs in 2. The
      period of normalisation of MEPs ranged between 1 and 6 months. CMCT correlated
      with motor and N9-N20 conduction time with sensory impairment. Eight patients had
      poor, 6 partial and 5 complete recovery. Power, sensation, CMCT, and size and
      location of haematoma made positive contributions to recovery.

PMID- 8869392
TI  - Automatic decomposition electromyography in idiopathic inflammatory myopathies.
AB  - Automatic decomposition electromyography (ADEMG) is a commercially available
      software package with installed reference values that enables the objective
      measurement of motor unit action potentials (MUAPs). To assess the diagnostic
      yield of this package in idiopathic inflammatory myopathies (IIM) we performed
      bicepts brachii ADEMG in 17 patients with polymyositis, dermatomyositis and
      inclusion body myositis. Results were compared with those in 12 controls, and
      with the results of conventional EMG of the biceps and other muscles. Decreased
      mean values for MUAP duration occurred significantly more frequently in IIM
      patients than in controls; other MUAP characteristics did not differ. In IIM
      patients, decreased mean amplitude and increased mean number of turns occurred
      significantly less frequently on ADEMG than did corresponding abnormalities on
      conventional biceps EMG. Decreased mean values for duration and amplitude, and
      increased mean values for number of turns were seen significantly less often on
      ADEMG than corresponding abnormalities on conventional EMG of four different,
      individually chosen muscles. Overall evaluation of ADEMG resulted in a diagnosis
      of "possible myopathy" in 1 and "probable myopathy" in 8 patients, whereas
      overall evaluation of conventional EMG led to a diagnosis "suggestive of IIM" in
      13 patients. We conclude that, although measurement of mean MUAP duration might
      be valuable in IIM diagnosis, our results do not favour the use of biceps brachii
      ADEMG and the installed reference values for the diagnosis of IIM. We suggest
      modifications to improve ADEMG's applicability.

PMID- 8869393
TI  - Squints and diplopia seen after brain damage.
AB  - The aim of this study was to investigate the incidence of squint after brain
      damage. We performed an observational study on 239 consecutive patients admitted
      to a specialist neurological rehabilitation unit: 129 with stroke, 84 with head
      injury and 26 with other conditions. Standard orthoptic measures, including
      visual acuity, cover test, eye movement recording and tests of binocular function
      were performed. Of all the patients, 89 (37%), were found to have squints, but
      only 32 of these (36%) experienced double vision. Brain stem lesions causing
      peripheral ocular motor impairment were found in a high proportion of patients
      after head injury (56%). Squints were found in 27 of 95 (28%) patients with
      cortical strokes, many with no other signs of brain stem involvement. Left was
      just as likely as right hemisphere damage to be associated with squint, but right
      sided lesions seemed to protect against diplopia. We conclude that squint is
      common after brain damage, even if the brain stem is not obviously affected, but
      only a minority of these patients with acquired squint suffer diplopia.

PMID- 8869394
TI  - Primary progressive multifocal leukoencephalopathy presenting as an
      extrapyramidal syndrome.
AB  - We report a 63-year-old woman with a progressive illness which began as a
      parkinsonian syndrome with bilateral rest tremor, limb rigidity and a gait
      disorder followed by cognitive decline, visuomotor apraxia and visual agnosia.
      She died 10 years after the onset of the illness and at autopsy the brain showed
      characteristic changes of progressive multifocal leukoencephalopathy (PML) with
      the presence of the JC virus confirmed by in situ hybridisation. Neuropathology
      also showed some unusual features in the form of atypical linear lesions at the
      cortico-white matter junction. Some of these lesions were active while others
      were inactive and similar to the rarely described "burnt out" lesions of PML. PML
      can in rare cases occur without an underlying immune disorder or malignancy
      (primary PML) and a parkinsonian syndrome can be produced by a predominantly
      white matter disorder.

PMID- 8869395
TI  - A study of prognostic predictors of supratentorial haematomas.
AB  - The prognosis of supratentorial haematomas is based on clinical signs and
      radiological features. The role of evoked potentials has not been evaluated
      systematically. In a prospective study of supratentorial haemorrhage a number of
      clinical (17), radiological (3) and evoked potential (2) parameters were
      evaluated employing univariate logistic regression analysis in 69 patients and
      multivariate logistic regression stepdown analysis in 51 patients. The outcome
      was graded on the basis of the Barthel index (BI) score at 3 months as good (BI >
      or = 12) or poor (death or BI < 12) recovery. Employing univariate analysis the
      significant prognostic variables were Glasgow Coma Scale, Canadian Neurological
      Scale, tendon reflex, associated medical complications, urinary incontinence,
      ventricular extension of the haematoma and motor evoked potentials. Using
      multivariate logistic regression analysis the best set of parameters in relation
      to outcome included Glasgow Coma Scale (P < 0.05), Canadian Neurological Scale (P
      < 0.05), tendon reflex (P < 0.1), ventricular extent (P < 0.01) and motor evoked
      potentials (P < 0.05). From this study it is concluded that, in addition to
      clinical and radiological parameters, motor evoked potentials also have an
      important role in predicting outcome.

PMID- 8869396
TI  - Cerebellar gait ataxia following neuroleptic malignant syndrome.

PMID- 8869397
TI  - Molecular basis of galactose-1-phosphate uridyltransferase deficiency involving
      skeletal muscle.

PMID- 8869398
TI  - An unusual sphenoid ridge tumor: cementifying fibroma.

PMID- 8869399
TI  - Stuttering, tic-like facial movements and behavioural disorders.

PMID- 8869400
TI  - Behaviour of human embryos in vitro in the first 14 days: blastocyst transfer and
      embryonic stem cell production.

PMID- 8869401
TI  - Human papillomavirus DNA testing in community screening for diseases of the
      cervix uteri.

PMID- 8869402
TI  - Chilli, capsaicin and the stomach.

PMID- 8869403
TI  - Treatment of male infertility with growth hormone.

PMID- 8869404
TI  - Human leucocyte antigens and nasopharyngeal carcinoma.

PMID- 8869405
TI  - Erythropoietin dysregulation in renal failure and research on IgA nephropathy.

PMID- 8869406
TI  - Cellular sodium pumps in hypokalaemic periodic muscle paralysis.

PMID- 8869407
TI  - Genetic basis of disease: studies of eicosanoids, and some complex disease
      traits.

PMID- 8869408
TI  - Endothelin peptides and receptors in human kidney.
AB  - 1. Animal kidneys are exquisitely sensitive to the vasoconstrictor and
      antinatriuretic effects of the endogenous vascular peptide endothelin. Animal
      studies have implicated endothelin in cyclosporin A and ischaemia-mediated renal
      damage. 2. In man, endothelin levels are raised in various disorders. Orally
      active endothelin antagonists are now being developed, but little was known of
      endothelin's role as a renal peptide in humans. These studies therefore aimed to
      characterize endothelin peptides and receptors ETA and ETB in human kidney, to
      direct potential therapeutic endeavours. 3. Ligand binding, immunocytochemical,
      radioimmunoassay and molecular biological studies were used to establish
      endothelin as a renal peptide in man. 4. The identification of species
      differences between man and rat directed further development of quantitative
      molecular biological methodology to permit analysis of endothelin receptors in
      human renal biopsies, and demonstrated perturbation of the system in the context
      of cyclosporin A therapy in renal transplantation.

PMID- 8869409
TI  - Supernormal left ventricular performance in young subjects with mild
      hypertension: an alerting response to the echocardiographic procedure?
AB  - 1. To assess the clinical significance of supernormal left ventricular systolic
      function in the initial phase of hypertension, 635 never-treated 18-45-year-old
      borderline to mild hypertensive subjects (477 males, 158 females) were studied.
      All subjects underwent echocardiography, 24 h ambulatory blood pressure
      monitoring and 24 h urine collection for catecholamine dosage. 2. Subjects whose
      left ventricular shortening-stress relationship was above the 95% confidence
      intervals of 50 normotensive subjects of similar age and sex distribution were
      defined as having supernormal function. 3. Age, duration of hypertension and left
      ventricular mass were similar in the hypertensive subjects with normal (85%) and
      supernormal (15%) ejective performance. Subjects with supernormal function showed
      higher office systolic blood pressure (P < 0001), office heart rate (P = 0.03)
      and cardiac index (P < 0001). Conversely, 24 h systolic blood pressure, 24 h
      heart rate and 24 h catecholamine output did not differ according to left
      ventricular function. 4. In conclusion, the greater white-coat effect and the
      normal baseline sympathetic tone exhibited by the patients with increased
      performance suggest that supernormal left ventricular pump function is only a
      marker of the alerting reaction elicited by the echocardiographic examination.

PMID- 8869410
TI  - Neutral endopeptidase inhibition: augmented atrial and brain natriuretic peptide,
      haemodynamic and natriuretic responses in ovine heart failure.
AB  - 1. Atrial and brain natriuretic peptide are both circulating hormones subject to
      degradation by neutral endopeptidase 24.11. Whereas endogenous levels of atrial
      natriuretic peptide are increased by neutral endopeptidase inhibition in most
      pathophysiological states, the effect on brain natriuretic peptide and the
      influence of cardiac status is less clear. To further evaluate the role of
      neutral endopeptidase 24.11, we directly compared the responses of atrial and
      brain natriuretic peptide, together with the effects on other vasoactive
      hormones, haemodynamics and renal indices, to a neutral endopeptidase inhibitor,
      SCH32615, and a vehicle control in eight conscious sheep before and during pacing
      induced heart failure. 2. In normal animals, SCH32615 significantly increased
      concentrations of plasma atrial natriuretic peptide (22 +/- 5 pmol/l compared
      with 14 +/- 2 pmol/l in control, 1.6-fold increase) and brain natriuretic peptide
      (6.5 +/- 1.2 pmol/l compared with 4.1 +/- 0.7 pmol/l in control, 1.6-fold
      increase), whereas in heart failure, plasma levels of atrial natriuretic peptide
      (306 +/- 38 pmol/l compared with 187 +/- 25 pmol/l in control, 1.6-fold increase)
      and brain natriuretic peptide (93 +/- 11 pmol/l compared with 55 +/- 9 pmol/l in
      control, 1.7-fold increase) were elevated to a significantly greater absolute,
      but proportionately similar, extent. In both normal and heart-failed animals,
      SCH32615 induced reductions in mean arterial pressure and left atrial pressure
      and increases in haematocrit, plasma cGMP and endogenous creatinine clearance.
      However, only in heart failure did neutral endopeptidase inhibition induce a
      significant and marked natriuresis (> 10-fold increase) and diuresis (4-fold
      increase), together with suppression of renin activity and haemodynamic effects
      including decreased peripheral resistance and raised cardiac output. 3. In
      conclusion, neutral endopeptidase inhibition increases plasma concentrations of
      atrial and brain natriuretic peptide to a proportionately similar extent in both
      normal and heart-failed sheep. The striking natriuresis and diuresis and
      additional haemodynamic effects demonstrated in sheep with heart failure, where
      natriuretic peptide levels are elevated compared with normal sheep, supports the
      concept that neutral endopeptidase inhibition augments endogenous atrial and
      brain natriuretic peptide.

PMID- 8869411
TI  - Behaviour of adrenomedullin during acute and chronic salt loading in normotensive
      and hypertensive subjects.
AB  - 1. Responses of adrenomedullin to acute and chronic salt loading were examined in
      normotensive and hypertensive subjects. 2. In the acute salt load study, isotonic
      saline (50 ml/kg for 1 h) was intravenously infused into nine normotensive
      subjects and 11 patients with essential hypertension. Plasma adrenomedullin was
      higher in hypertensive than in normotensive subjects but was unchanged by saline
      infusion in either the normotensive (before infusion, 2.4 +/- 0.2 fmol/ml; after
      infusion, 2.4 +/- 0.1 fmol/ml) or hypertensive (before infusion, 3.0 +/- 0.1
      fmol/ml; after infusion, 2.9 +/- 0.2 fmol/ml) group, while renin was suppressed
      and atrial natriuretic peptide was markedly increased. Plasma endothelin was not
      affected either. 3. In the chronic salt load study, seven normotensive subjects
      and 23 patients with essential hypertension underwent two 7-day periods of 30 and
      260 mmol/day sodium intake. Depending on the blood pressure change, 13
      hypertensive subjects were classified as salt-resistant and 10 as salt-sensitive.
      Salt-sensitive hypertensive subjects had suppressed plasma renin activity even
      during low salt intake. Plasma adrenomedullin or endothelin were not affected by
      the salt intake changes in any group; however, the high salt intake increased
      atrial natriuretic peptide in all groups. 4. These data indicate that the
      circulating level of adrenomedullin is not changed by either acute or chronic
      salt loading in normotensive subjects and patients with essential hypertension.

PMID- 8869412
TI  - Mechanism of the impaired natriuretic response to frusemide during sodium
      depletion: a micropuncture study in rats.
AB  - 1. The nephron sites involved in the blunted natriuretic response to frusemide
      during sodium depletion were investigated using micropuncture techniques in
      anaesthetized rats. 2. Glomerular filtration rate was lower, and fractional
      sodium reabsorption in the proximal convoluted tubule higher, in sodium-depleted
      than in sodium-replete rats. Consequently, sodium delivery to the loop of Henle
      was reduced (by approximately 35%) in the sodium-depleted animals. Intravenous
      frusemide (2.5 mg h-1 kg-1; urinary water and electrolyte losses replaced) had no
      effect on glomerular filtration rate or proximal tubular sodium reabsorption in
      either group. 3. The inhibitory effect of intravenous frusemide on fractional
      sodium reabsorption in the nephron segments constituting the loop of Henle
      (measured by free-flow micropuncture) was attenuated during sodium depletion.
      However, when loops of Henle were microperfused at identical rates with
      artificial late proximal tubular fluid, no difference in the responses of sodium
      depleted and sodium-replete rats to intraluminal frusemide (10(-5) mol/l) could
      be detected. 4. In sodium-replete animals, the increased load of sodium delivered
      from the loop of Henle during frusemide administration resulted in a lowering of
      fractional sodium reabsorption in the distal tubule. In contrast, in sodium
      depleted rats given frusemide, fractional distal sodium reabsorption tended to
      increase, so that values in the two groups of frusemide-treated animals were
      markedly different (0.30 +/- 0.04 versus 0.51 +/- 0.03). 5. It is concluded that
      the blunted natriuretic response to frusemide during sodium depletion results
      from at least three factors: a reduced sodium delivery to the loop of Henle; a
      reduced inhibitory effect of frusemide on fractional sodium reabsorption in the
      loop of Henle, which may be a consequence of the reduced sodium load; and
      enhanced fractional reabsorption of sodium in the distal tubule, which partially
      buffers the diuretic-induced increase in sodium delivery from the loop.

PMID- 8869413
TI  - Rates of bone loss in peri- and postmenopausal women: a 4 year, prospective,
      population-based study.
AB  - 1. Age-related bone loss is well established but reported rates of bone loss in
      the spine and femur vary widely. The aim of the present study was to investigate
      changes in bone mineral density in the lumbar spine and proximal femur in healthy
      postmenopausal women. 2. One hundred and thirty-eight population-based women,
      aged 45-65 years, recruited from general practice registers in 1990, were
      assessed at baseline; 108 returned for repeat assessment 4 years later, of whom
      31 had taken hormone replacement therapy for 12 months or more of the 4-year
      study period. Bone densitometry of the lumbar spine and proximal femur was
      performed by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D and
      oestradiol were measured by RIA and serum intact parathyroid hormone by radio
      immunometric assay. 3. The mean age at follow-up was 62 years (mean of 13.6 years
      after menopause). Lumbar spine bone mineral density was significantly higher in
      women who had received hormone replacement therapy for more than 12 months during
      the study period than in those who had not (P < 0.01). There was no difference
      between these two groups in the femoral neck or trochanteric bone mineral
      density. In the lumbar spine, the annual change in bone mass in untreated women
      was -0.39% (95% confidence intervals -0.60 to -0.09; P < 0.02) whereas there was
      a small gain in women receiving hormone replacement therapy [+0.36% (-0.12 to
      0.84; P not significant)]. The annual change in bone mass in the femoral neck and
      trochanter was -0.51 and -0.45 respectively in untreated women (P < 0.01 and P <
      0.02), and -0.16 and -0.15 in those receiving hormone replacement therapy (P not
      significant). 4. Our results demonstrate relatively low rates of bone loss in the
      spine and proximal femur in these healthy, population-based peri- and
      postmenopausal women. Hormone replacement therapy appeared to be associated with
      a significant protective effect on spinal, but not femoral, bone mineral density.

PMID- 8869414
TI  - Effects of mineral composition of drinking water on risk for stone formation and
      bone metabolism in idiopathic calcium nephrolithiasis.
AB  - 1. To assess whether the mineral content of drinking water influences both risk
      of stone formation and bone metabolism in idiopathic calcium nephrolithiasis, 21
      patients were switched from their usual home diets to a 10 mmol calcium, low
      oxalate, protein-controlled diet, supplemented with 21 of three different types
      of mineral water. Drinking water added 1, 6 and 20 mmol of calcium and 0.5, 10
      and 50 mmol of bicarbonate respectively to the controlled diet. 2. The three
      controlled study periods lasted 1 month each and were separated by a 20 day
      washout interval. Blood and urine chemistries, including intact parathyroid
      hormone, calcitriol and two markers of bone resorption, were performed at the end
      of each study period. The stone-forming risk was assessed by calculating urine
      saturation with calcium oxalate (beta CaOx), calcium phosphate (beta bsh) and
      uric acid (beta UA). 3. The addition of any mineral water produced the expected
      increase in urine output and was associated with similar decreases in beta CaOx
      and beta UA, whereas beta bsh varied marginally. These equal decreases in beta
      CaOx, however, resulted from peculiar changes in calcium, oxalate and citrate
      excretion during each study period. The increase in overall calcium intake due to
      different drinking water induced modest increases in calcium excretion, whereas
      oxalate excretion tended to decrease. The changes in oxalate excretion during any
      one study period compared with another were significantly related to those in
      calcium intake. Citrate excretion was significantly higher with the high-calcium,
      alkaline water. 4. Parathyroid hormone, calcitriol and markers of bone resorption
      increased when patients were changed from the high-calcium, alkaline to the low
      calcium drinking water. 5. We suggest that overall calcium intake may be tailored
      by supplying calcium in drinking water. Adverse effects on bone turnover with low
      calcium diets can be prevented by giving high-calcium, alkaline drinking water,
      and the stone-forming risk can be decreased as effectively as with low-calcium
      drinking water.

PMID- 8869415
TI  - Phenotypic and quantitative changes in mast cells after syngeneic unilateral lung
      transplantation in the rat.
AB  - 1. Lung transplantation causes a total interruption of the inneration and
      vascularization within the transplanted organ, followed by repair processes. This
      is frequently associated with bronchial hyper-responsiveness. A common feature of
      tissue repair is an increase in the number of mast cells. Three phenotypically
      distinct mast cell subsets, with respect to their protease content, have been
      identified in rat lung, and it is probable that mast cells of differing protease
      phenotype fulfil different functions. 2. We have compared the number, protease
      phenotype and distribution of mast cells in left lung from transplanted and
      control Lewis rats 1 month after syngeneic unilateral left lung transplantation,
      without interference of inflammation, graft rejection or of any treatment.
      Connective and mucosal-type mast cell phenotypes were characterized using
      antibodies directed against their specific rat mast cell proteases, RMCPI and
      RMCPII, respectively. 3. After transplantation, RMCPI and RMCPII tissue
      concentrations increased by 172% and 239%, respectively, compared with controls
      (13.1 +/- 1.2 and 5.6 +/- 1.0 micrograms/g). 4. Localization of mast cell
      phenotypes was studied by immunohistochemistry after double immunostaining. The
      number of mast cells increased after transplantation: the increase in the number
      of RMCPI-immunoreactive mast cells (RMCPI+) was significant around bronchioles
      and arterioles, around large vessels and in the pleura. The number of RMCPII+
      mast cells also significantly increased around bronchioles and arterioles, as
      well as in the smooth muscle layer of large airways. Some mast cells stained for
      the presence of both RMCPI and RMCPII, supporting the existence of co-expressing
      phenotype in rat lung. The number of mast cells of the RMCPI+/II+ phenotype
      significantly increased around bronchioles and arterioles and in the pleura.
      Moreover, the distribution of the mast cell phenotypes was modified in the
      different areas after transplantation. 5. This indicates a local
      differentiation/maturation of mast cells after transplantation.

PMID- 8869416
TI  - Relationship between granulocyte activation, pulmonary granulocyte kinetics and
      alveolar permeability in extrapulmonary inflammatory disease.
AB  - 1. The aim of the study was to examine the relationship between granulocyte
      activation, pulmonary intravascular granulocyte transit, pulmonary extravascular
      granulocyte migration and lung injury in patients with systemic conditions (bone
      marrow transplant recipients, inflammatory bowel disease and systemic vasculitis)
      in which abnormalities of pulmonary granulocyte traffic have previously been
      reported. 2. A double 111In-99mTc granulocyte labelling technique was used for
      quantification of granulocyte kinetics in 23 patients, of whom five were control
      patients. The pulmonary vascular granulocyte pool was measured from dynamic data
      centred on the 99mTc signal and expressed as a percentage of the total blood
      granulocyte pool. Granulocyte migration was quantified on 24 h images using the
      111In signal. Granulocyte activation was measured as the percentage of cells
      showing a change in shape. The clearance rate of an inhaled aerosol of 99mTc
      diethylenetriaminepenta-acetic acid (DTPA) was used as a marker of lung injury.
      3. Pulmonary granulocyte pool, migration, activation and aerosol clearance,
      although highly variable in the patient groups, were, in general, elevated
      compared with the controls. 4. Granulocyte activation correlated with pulmonary
      granulocyte pool (Rs = 0.72, n = 22, P < 0.01), while the t1/2 of DTPA clearance
      correlated with migration (Rs = -0.84, n = 17, P < 0.01). Fifteen patients had an
      expanded pulmonary granulocyte pool, of whom six with no evidence of migration,
      had a normal DTPA clearance, while nine, who had an abnormal migration signal,
      had an accelerated DTPA clearance. The pulmonary granulocyte pool in these nine
      was significantly higher than in the six without a migration signal. 5.
      Activation of granulocytes results in delayed transit through the lung
      vasculature. With increasing margination, granulocytes migrate into the lung
      interstitium and injure the lung. An increased intravascular pool does not by
      itself lead to lung injury.

PMID- 8869417
TI  - Effect of almitrine on ventilation and on diaphragm and geniohyoid muscle
      activity in the rat.
AB  - 1. Ventilation was measured during normoxia, hypoxia and hypercapnia before and
      after administration of almitrine in conscious, unrestrained, tracheostomized
      rats with the superior laryngeal nerves intact or cut. In superior laryngeal
      nerve-intact animals breathing air, almitrine increased minute ventilation due to
      an increase in respiratory frequency with no change in tidal volume. In superior
      laryngeal nerve-sectioned animals, the minute ventilatory response to almitrine
      was reduced due to a reduced tidal volume component of the response. Almitrine
      increased the ventilatory response to hypercapnia in superior laryngeal nerve
      intact but not in sectioned animals. 2. In anaesthetized, vagotomized rats
      breathing spontaneously through a low-cervical tracheostomy, diaphragm and
      geniohyoid electromyographic activities were recorded. Arterial blood pressure
      and rectal temperature were continuously monitored. A single dose of almitrine
      was administered intravenously. In all animals, the geniohyoid muscle had phasic
      inspiratory activity which slightly preceded diaphragm activity. Almitrine had no
      effect on respiratory frequency or inspiratory and expiratory duration but
      increased mean peak integrated diaphragm (+29.3 +/- 13.6%) and geniohyoid (+132.0
      +/- 21.3%) muscle activity. 3. These results show that almitrine exerts part of
      its ventilatory effects through superior laryngeal nerve afferents. Almitrine
      preferentially excites upper airway compared with diaphragm muscle activity,
      suggesting a potential role in the alleviation of obstructive apnoea.

PMID- 8869418
TI  - Plasma ionized magnesium during acute hyperventilation in humans.
AB  - 1. Respiratory alkalosis accompanies the clinical syndrome of tetany,
      precipitates cardiac arrhythmias and predisposes to coronary vasoconstriction.
      Magnesium plays a critical role in the maintenance of membrane function, and
      magnesium depletion is often associated with cardiac arrhythmias or
      vasoconstriction. 2. As technology for detecting circulating ionized magnesium
      (the most interesting form with respect to physiological and biological
      properties) is now available in the form of new magnesium-selective electrodes,
      the effect of respiratory alkalosis induced by voluntary overbreathing for 30 min
      on circulating ionized magnesium was studied in eight healthy subjects. 3. The
      total plasma magnesium concentration was not modified by hyperventilation. On the
      contrary, hyperventilation was associated with a significant reduction in the
      ionized magnesium concentration of 0.05 (0.02-0.15) mmol/l (median and range) and
      in the free magnesium fraction of 0.06 (0.01-0.19). During hyperventilation the
      relative intravascular magnesium mass, calculated from changes in total plasma
      magnesium concentration and haematocrit, decreased significantly. 4. It is
      concluded that acute overbreathing reduces the circulating ionized magnesium
      concentration and the intravascular magnesium mass. It is therefore conceivable
      that extracellular magnesium deficiency is at least a subsidiary cause of the
      syndrome of tetany and the cardiac complications that are precipitated by
      hyperventilation.

PMID- 8869419
TI  - Human erythrocyte choline uptake in uraemia: the role of intracellular substrate
      and an investigation into the effects of haemodialysis.
AB  - 1. Erythrocyte choline transport was studied in 10 haemodialysis patients
      immediately before and after a haemodialysis session and in 10 control subjects.
      Choline uptake was measured in erythrocytes from normal and uraemic patients
      after washing in vitro and subsequent incubation in autologous plasma. Amines
      present in uraemic plasma were examined for their effect on choline transport in
      normal erythrocytes. 2. NMR spectroscopy was used to measure choline,
      trimethylamine and dimethylamine in erythrocyte extracts from nine control
      subjects, 32 subjects with renal impairment and nine samples from haemodialysis
      patients. 3. The increased choline influx in uraemic erythrocytes is
      significantly decreased by prior haemodialysis (mean Vmax pre-dialysis 146 +/- 20
      mumol h-1 l-1, post-dialysis 113 +/- 13 mumol h-1 l-1 (P < 0.005). After in vitro
      washing there is a fall in Vmax, and no longer any significant difference between
      pre- and post-dialysis samples. There remains a significant difference in the
      erythrocyte choline Vmax between samples from patients with chronic renal failure
      and from normal subjects (P < 0.005). 4. Human plasma was found to contain
      factors capable of increasing choline uptake. Trimethylamine and dimethylamine
      were found to inhibit choline uptake. Trimethylamine and trimethylamine-N-oxide
      trans-stimulated choline efflux, but the major transport substrate present in
      erythrocyte extracts from all groups was choline, which was higher in those with
      renal impairment (71 +/- 10 mumol/l) than in haemodialysis patients (47 +/- 10
      mumol/l) and control subjects with normal renal function (40 +/- 9 mumol/l). 5.
      Our data suggest that erythrocyte choline transport is increased in uraemia as a
      consequence of increased transporter number or activity, rather than the presence
      of intracellular substrate.

PMID- 8869420
TI  - Stimulation of colonic mucin synthesis by corticosteroids and nicotine.
AB  - 1. We speculated that corticosteroids might cause beneficial stimulation of mucus
      synthesis, since this is a known action of carbenoxolone, itself a
      corticosteroid, and has also been proposed as a possible mechanism for the
      protective effect of smoking on ulcerative colitis. We have therefore compared
      the effects of corticosteroids including carbenoxolone, and nicotine on mucin
      synthesis, assessed by incorporation of N-[3H]acetylglucosamine into mucin by
      colonic epithelial biopsies in culture. 2. In histologically normal biopsies from
      the left colon, hydrocortisone and prednisolone caused a very marked
      concentration-dependent increase in mucin synthesis, with maximal effect (580 and
      300% of control values respectively) at 6 mumol/l [P < 0.001, n = 35 biopsies
      (seven patients)] and 1.5 mumol/l [P < 0.001, n = 35 (seven patients)]
      respectively. The maximal effect of hydrocortisone was significantly greater than
      that of prednisolone (P < 0.05). Carbenoxolone, 0.17 mmol/l, also increased mucin
      synthesis in the left colon by 242% [P < 0.05, n = 15 (three patients)]. In
      contrast, these corticosteroids caused only a small, non-significant increase in
      mucin synthesis in the histologically normal right colon; fludrocortisone, 2 and
      20 mumol/l, and aldosterone, 0.1-10 mumol/l, had no effect. Nicotine
      significantly increased mucin synthesis (180-220% of control values) between 62.5
      nmol/l and 6.25 mumol/l (P < 0.05 at all concentrations) in both the right and
      left colon. In biopsies from the relatively uninvolved right colon of patients
      with ulcerative colitis, corticosteroids and nicotine caused relatively smaller
      increases in mucin synthesis. 3. The marked stimulation of mucin synthesis by
      corticosteroids suggests that this may account, at least in part, for their
      therapeutic effect in ulcerative colitis.

PMID- 8869421
TI  - Impairment of intracellular calcium homoeostasis in the exocrine pancreas after
      caerulein-induced acute pancreatitis in the rat.
AB  - 1. We have measured intracellular calcium concentrations in basal conditions and
      in response to cholecystokinin-octapeptide and acetylcholine in pancreatic acini
      isolated from rats with caerulein-induced acute pancreatitis and compared them
      with those in control rats. 2. We also measured amylase secretion in basal
      conditions and in response to cholecystokinin-octapeptide in both groups. 3. In
      pancreatic acini from rats with pancreatitis the basal intracellular calcium
      concentration was significantly increased (134.9 +/- 7.1 nmol/l compared with
      71.8 +/- 2.9 nmol/l, P < 0.001). Moreover, the maximum values of intracellular
      calcium attained during the stimulation period were equivalent in acini from
      control and pancreatitic rats with no statistically significant differences. 4.
      In acini from control rats the differences between the resting levels of
      intracellular calcium and the maximum intracellular calcium values (delta[Ca2+]i)
      in response to several concentrations of cholecystokinin-octapeptide showed a
      clear dose-response relationship, with a half-maximal increase at 0.1 nmol/l and
      a maximal difference (delta[Ca2+]i = 259 +/- 50 nmol/l) at 1 nmol/l. In contrast,
      a right-shifted response, with a statistically significant smaller increase, was
      observed in acini from pancreatitic rats. 5. Basal amylase release was
      significantly higher in acini from rats with pancreatitis (11.7 +/- 1.0% of total
      compared with 5.9 +/- 1.1% of total, P < 0.001). In contrast, cholecystokinin
      octapeptide and acetyl-choline-evoked amylase secretion was reduced by more than
      85% in acini from pancreatitic rats. 6. In conclusion, calcium homoeostasis in
      pancreatic acinar cells from rats with caerulein-induced pancreatitis seems to be
      impaired. These results suggest excessive release of acinar free ionized calcium,
      or damage to the integrity of mechanisms that restore low resting levels of
      intracellular free ionized calcium, and the consequent calcium toxicity could be
      the key trigger in caerulein-induced acute pancreatitis.

PMID- 8869422
TI  - Neutrophil adhesion molecule expression and response to stimulation with
      bacterial wall products in humans is unaffected by parenteral nutrition.
AB  - 1. Total parenteral nutrition is associated with a high incidence of septic
      complications. This may be partly due to neutrophil dysfunction induced by the
      parenteral nutrition. 2. Neutrophil adhesion molecule expression and the
      expression of CD11b in response to stimulation with formylmethionyl-leucyl
      phenylalanine and lipopolysaccharide were determined before and after 24 h of
      lipid-containing parenteral nutrition. Eighteen adult patients referred for
      parenteral nutrition were studied. 3. There was no change in the expression of
      neutrophil L-selectin (CD62L), CD11a, CD11b, CD11c or CD15. Neutrophil response
      to stimulation with formylmethionyl-leucyl-phenylalanine and lipopolysaccharide
      as determined by CD11b expression was unaffected by parenteral nutrition. 4. This
      study has shown no evidence of parenteral nutrition-induced neutrophil
      dysfunction.

PMID- 8869423
TI  - Study of neurons and glial cells of basolateral amygdala in male and female rats
      neonatally treated with estrogen.
AB  - The influence of estrogen on the neurons and glial cells was examined in the
      phylogenetically younger, basolateral part of neonatal rat amygdala (nucleus
      basolateralis and nucleus lateralis posterior). Neonatal rats were treated with a
      single dose of 1 mg of estrogen on the postnatal day 3, and the [3H]--thymidine
      ([3H] TdR) incorporation was studied by means of autoradiography. On the
      postnatal day 10, in treated rats, the percentages of labeled neurons and glial
      cells significantly increased in nearly all of the nuclei investigated. The only
      exception was the unchanged percentage of labeled glial cells in the treated
      female rats (in both of investigated nuclei).

PMID- 8869424
TI  - The pineal gland, cataplexy, and multiple sclerosis.
AB  - Since the discovery of melatonin as the principal hormone of the pineal gland in
      1963, scientists have come to recognize that melatonin is a "master hormone"
      involved in the control of circadian rhythms and other biological functions.
      Although little is known about the influence of the pineal gland on motor
      control, important clues may be obtained by considering the pattern of melatonin
      secretion during the sleep cycles and particularly during rapid eye movement
      (REM) sleep when melatonin plasma levels are at their lowest. Since REM sleep is
      characterized by the occurrence of profound atonia which results in an almost
      complete paralysis of striated muscles, it is suggested that there might be a
      causal relationship between inhibition of melatonin secretion during REM sleep
      and the development of REM sleep atonia. This relationship is supported by the
      findings that melatonin regulates the activity of brainstem serotonin (5-HT)
      neurons which characteristically cease to fire during REM sleep and which
      faciliate the development of REM sleep atonia. Moreover, as the muscular atonia
      of REM sleep is physiologically and pharmacologically indistinguishable from
      cataplexy, it is possible that the pineal gland also influences to the
      development of cataplexy. Cataplexy is an ancillary symptom of narcolepsy and
      also occurs in multiple sclerosis (MS). In fact, it is believed that several of
      the neurological symptoms experienced by patients with MS such as weakness in the
      legs, feeling of collapsing knees, paroxysmal sudden falling, weakness in the
      neck, extreme fatigue, intermittent paresthesias, slurring of speech and
      intermittent blurring of vision, which often are exacerbated by stress and other
      emotional influences, may reflect the manifestations of cataplexy. Thus, several
      of the clinical features of MS may reflect a dissociated state of wakefulness and
      sleep and may improve by the administration of anticataplectic drugs.

PMID- 8869425
TI  - Cysteamine attenuates iminodipropionitrile (IDPN) induced dyskinesia in rats.
AB  - The present investigation was undertaken to study the effect of cysteamine on
      experimental dyskinesia in rats. The movement disorders were produced by
      intraperitoneal administration of iminodipropionitrile (IDPN) in the dose of 100
      mg/kg per day for 11 days. Cysteamine was administered (i.p.), daily 30 minutes
      before IDPN in the doses of 25 mg/kg, 50 mg/kg and 100 mg/kg bodyweight in three
      different groups of rats. Twenty four hours after the last dose of IDPN, animals
      were observed for neurobehavioural changes including vertical and horizontal head
      weaving, circling, backwalking, grip strength and righting reflex. Immediately
      after behavioural studies brain specimens were collected for analysis of vitamin
      E and total glutathione levels. The results of behavioural studies showed that co
      treatment with cysteamine protected rats against IDPN-induced dyskinesia. Our
      biochemical studies showed that IDPN produced a depletion of vitamin E in
      cerebrum, cerebellum and brain stem. Concomitant treatment with cysteamine in
      doses of 50 and 100 mg/kg attenuated IDPN-induced decrease in vitamin E in
      cerebrum and cerebellum. There was a significant decrease in cerebral glutathione
      in IDPN treated rats, which was attenuated by cysteamine. No significant change
      was observed in the glutathione levels in cerebellum and brain stem. Further
      studies are deemed necessary to elucidate the mode of action of cysteamine and to
      determine therapeutic and/or prophylactic value of this drug in the treatment of
      movement disorders.

PMID- 8869426
TI  - Defensive behavior induced by stimulation of the ventral striatum in the cat.
AB  - The behavioral responses induced by electrical stimulation of the ventral
      striatum were studied in 15 freely moving cats, chronically implanted with
      multiwire electrodes. Two types of defensive responses could be evoked from the
      ventral striatum, an arrest response and an escape or flight reaction.
      Stimulation of the dorsal striatum and the internal capsule induced contralateral
      head turning and movements of the face or limbs. The number of ventral striatal
      sites eliciting escape responses increased along the sessions, while their
      threshold decreased. Lesioning the ventral pallidal region with kainic acid
      increased significantly the threshold for defensive responses, whereas head
      turning responses showed no change. The results of this study indicate that the
      ventral striatum could be part of the neural substrate for defensive behavior,
      and that the ventral pallidal region plays a role in its mediation.

PMID- 8869427
TI  - Premenstrual exacerbation of symptoms in multiple sclerosis is attenuated by
      treatment with weak electromagnetic fields.
AB  - It has been suspected that hormonal factors contribute to the etiology and
      pathogenesis of multiple sclerosis (MS). A direct relationship between MS and
      endocrine functions is suggested by changes in disease activity during the phases
      of the menstrual cycle. A subset of women with MS experience premenstrual
      worsening of symptoms which improve dramatically with the onset of menstruation.
      The biological mechanisms underlying these changes in disease activity are
      unexplained but may be related to cyclical fluctuations in gonadal sex steroid
      hormones, abrupt changes in the activity of the endogenous opioid peptides and
      fluctuations in plasma melatonin levels which affect neuronal excitability and
      immune functions. Extracerebral application of weak electromagnetic fields (EMFs)
      in the picotesla range intensity has been reported efficacious in the treatment
      of MS with patients experiencing sustained improvement in motor, sensory,
      autonomic, affective and cognitive functions. The present report concerns two
      women with chronic progressive stage MS who experienced, coincident with
      increasing functional disability, regular worsening of their symptoms beginning
      about a week before menstruation and abating with the onset of menstruation.
      These symptoms resolved two months after the initiation of treatment with EMFs.
      The report supports the association between the endocrine system and MS and
      indicates that brief, extracranial applications of these magnetic fields modifies
      the activity of neuroendocrine systems which precipitate worsening of MS symptoms
      premenstrually.

PMID- 8869428
TI  - Ultradian rhythms in performance on tests of specialized cognitive function.
AB  - Performance on cognitive tasks cycled at ultradian frequencies for 24 males over
      a test period of eight hours. The verbal task of written word production cycled
      at 80 minutes; the spatial task of locating points in space cycled at 96 minutes.
      Multiple cycles were seen for a perceptual speed task that factor loads on both
      the verbal and spatial task. Replication of the results for the first 12 and
      second 12 subjects demonstrated their robustness. The verbal and spatial tasks
      were chosen to reflect specialized functions of the left and right cerebral
      hemispheres, respectively. Accordingly, the results are interpreted as evidence
      that specialized task performances are associated with independent neurochemical
      systems. In addition, blood samples were taken at task performance to assess
      cyclicity of hormone levels. Luteinizing hormone had a period of 120 minutes,
      testosterone and cortisol were inconsistent and none seemed to be related to the
      cognitive tasks. However when subjects were divided according to a winter or
      summer testing schedule, the spatial periodicity was absent for the summer group
      and the verbal periodicity was absent for the winter peak.

PMID- 8869429
TI  - Visual evoked potentials generator model derived from different spatial frequency
      stimuli of visual field regions and magnetic resonance imaging coordinates of V1,
      V2, V3 areas in man.
AB  - Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli were
      recorded from 24 scalp derivations (including zygomatic and inion) referenced to
      digitally linked earlobes in 50 controls. 1, 2 and 4 cpd patterns were presented
      as full field (FF) stimuli, on Upper Hemifields (UHF) and Lower Hemifields (LHF),
      upper and lower quadrants and with the occlusion of central and peripheral UHF
      and LHF. VEPs to octant stimuli were also recorded with 2 cpd patterns. N1, P1
      and N2 components were recorded from posterior and inion derivations with FF
      stimuli, from posterior derivations with LHF stimuli, only from inion leads with
      UHF stimuli, from derivations ipsilateral to stimuli with quadrants and octants,
      and consistently from midline derivations only with lower quadrants. Polarity
      inverted sequences (iN1-iP1-iN2) were recorded from the other scalp derivations,
      with similar latency and spatial frequency sensitivity as N1-P1-N2. Single
      Equivalent Dipole (ED) calculations were performed on N1 and P1 recorded in the
      different stimulus conditions. Our findings contradict previous hypotheses on VEP
      generators and contradict the predictions of VEPs polarity and distribution based
      on the "cruciform model" of VEPs generators. In order to explain the distribution
      of VEPs to upper and lower half fields and to quadrant and octants, we propose a
      model based on the position of the medial and occipito-polar surface of visual
      cortex in man.

PMID- 8869430
TI  - Visual deprivation at the critical period modulates photic evoked responses.
AB  - Average visual evoked responses (AVER) were recorded from the striate cortex of
      normal (control) and monocular visually deprived Long-Evans hooded rats. One
      month of monocular visual deprivation (MD) at the critical period of development
      resulted in marked reduction of all the three AVER components (i.e., components
      P2, N2 and P3) as compared to the control recording (P < 0.001). In control
      animals, the AVER amplitudes of the two hemispheres were identical, while in MD
      rats, the P2 and N2 components of the AVER obtained from the hemisphere
      ipsilateral to the MD eye were markedly smaller than those of the AVER obtained
      from the contralateral hemisphere (P < 0.001). The latencies of the late
      components (N2 and P3) obtained from the hemisphere ipsilateral to the MD eyes
      were significantly delayed as compared to those from the contralateral hemisphere
      (P < 0.05 for N2, P < 0.01 for P3). The AVER following paired photic stimuli with
      various time intervals between the stimuli were used to study the neuronal
      recovery function of control animals compared to MD animals. The AVER to the
      second stimulus obtained from the MD rats exhibited greater attenuation in their
      amplitude responses than the AVER obtained from the control group, i.e., slower
      neuronal recovery. The neurophysiological changes observed in this study may
      relate to the neurocytological alteration occurring in the striate cortex
      following monocular visual deprivation at the critical period. In conclusion,
      AVER recorded from monocular visually deprived rats during the critical period is
      a simple and reliable electrophysiological animal model to study neuroplasticity
      during postnatal development.

PMID- 8869431
TI  - Middle latency auditory evoked potentials in intensive care patients and normal
      controls.
AB  - Evoked potentials have been introduced into intensive care unit to objectively
      measure parameters of coma. In particular, auditory brainstem evoked potentials
      have been useful for localizing brainstem dysfunction in comatose patients. The
      middle latency auditory evoked potentials (MLAEPs) believed to be a response of
      subcortical auditory radiations and the primary auditory cortex. MLAEPs were
      measured in 40 adults (mean age 24.9 +/- 2.9 years; range: 19-34 years) with
      normal hearing and in 102 intensive care patients (mean age: 48.4 +/- 18.9 years;
      range: 14-86 years) under the influence of biological variables. Latencies
      (control group, mean +/- SD: V = 5.74 +/- .29 ms, N0 = 9.11 +/- 1.74 ms, P0 =
      12.94 +/- 1.87 ms, Na = 17.23 +/- 1.77 ms, and Pa = 29.22 +/- 3.43 ms),
      amplitudes (control group, mean +/- SE: N0-P0 = 2.00 +/- .34 microV, P0-Na = 3.88
      +/- .67 microV, Na-Pa = 2.83 +/- .29 microV) and the amplitude ratio (control
      group, mean +/- SE: P0-Na/Na-Pa = 1.53 +/- .39) were calculated. In the control
      group in both females and males, right-sided stimulation produced shorter average
      MLAEP latencies and higher amplitudes than left-sided stimulation (Pa-right 28.26
      +/- 3.53 ms; Pa-left 30.17 +/- 3.33 ms). MLAEPs showed significant differences
      according to sex but did not depend significantly on age. A temperature
      dependence was found for the latency of wave V (short latency AEP), which was
      prolonged at lower temperatures and for the amplitude Na-Pa, which was increased
      at decreased temperatures between 38.9 and 35.4 degrees C. There was a
      significant association between the amplitude Na-Pa and PO2 (P = .017).
      Alterations of PCO2 in the range of 26 to 54 mmHg did not influence the MLAEPs.
      Also, renal dysfunction or hepatic dysfunction and alterations of mean arterial
      pressure (range: 50-102 mmHg) did not affect MLAEP latencies and amplitudes
      significantly. Increases in latencies and decreases in amplitude were seen in
      sedated patients. These results in intensive care patients suggest that the
      combination of early AEP (acute phase) and MLAEP (post acute phase) may be useful
      to monitor comatose patients.

PMID- 8869432
TI  - Cognitive estimation in traumatic brain injury: relationships with measures of
      intelligence, memory, and affect.
AB  - Brain injury is associated with a reduced capcity to engage in effective
      cognitive estimation. The current study utilized two measures of this construct,
      the Cognitive Estimation Test (CET) and Luria Memory Test (Luria), to investigate
      the relationships between cognitive estimation and intelligence, memory, and
      affect in a sample of 30 traumatically brain-injured individuals. Results
      demonstrated significant correlations between cognitive estimation and tests of
      intelligence and memory. However, measures of depression and state anxiety were
      not meaningfully associated with cognitive estimation. The ability to recall
      stories accounted for the greatest portion of the variance for both the CET and
      Luria. Specifically, the 30-minute Logical Memory subtest from the Wechsler
      Memory Scale-Revised accounted for 38% of the variance in the CET, while the
      Logical Memory 30-minute savings score accounted for 47% of the variance in the
      Luria. Intellectual and affective variables explained only negligible amounts of
      variance on cognitive estimation tasks.

PMID- 8869433
TI  - Limb laterality and motor proficiency in children.
AB  - This investigation examined the premise derived from recent reports, that
      children who are consistent right-handers are better coordinated than their left-
      and mixed-sided (inconsistent) peers. The observation of limb laterality was
      extended to include footedness. Two samples of children (N = 273) (foot
      laterality/hand laterality), matched for age and sex, were assessed for motor
      proficiency and compared according to limb preference (right, mixed, left).
      Overall, results indicated no significant group differences (ps > .05) in
      composite scores (upper-limb, lower-limb, combination) and total performance,
      within foot and hand laterality. In view of recent studies (noting differences
      between laterality groups) and these nonsupportive results, it appears that
      additional inquiry is warranted before any consensus regarding the association
      between limb laterality and motor coordination can be established. Suggestions
      for further inquiry are presented.

PMID- 8869434
TI  - Effect of manipulating visual feedback parameters on eye and finger movements.
AB  - Thirteen healthy subjects were asked to maintain a constant index finger position
      in Experiment 1 or a constant eye position in Experiment 2 using visual feedback.
      The finger or eye position along with a stationary baseline target was displayed
      on an oscilloscope placed in front of the subject. Experiments 1 and 2 were
      carried out under sixteen combinations of delay and amplification of displacement
      on the screen (i.e., gain). In Experiment 1, increasing the gain in the visual
      feedback decreased the Root Mean Square (RMS) errors while increasing the delay
      increased these errors. An interaction between gains and delays was also observed
      in Experiment 1. In Experiment 2, the RMS errors were systematically higher than
      those recorded in Experiment 1 for the finger. No systematic pattern was
      recognized across all conditions of gains and delays for eye movements in
      Experiment 2. This study clearly illustrates differences in dynamics of motor
      control systems regulating eye and finger positions, respectively.

PMID- 8869435
TI  - Allergen avoidance measures. British Thoracic Society.

PMID- 8869436
TI  - Definitions of severity and outcome measures.
AB  - Outcome measurement is still a difficult area in general, and in asthma in
      particular, with further research needed. (Attributable) outcomes of health care
      are the only sort of outcome measure which are of direct use as a contracting
      tool. However, less well-researched and understood outcomes are useful as quality
      improvement tools, and within more open-ended discussions involving purchasers
      and providers. In terms of hospital care of acute asthma, there is no well
      defined outcome measure which reflects the quality of hospital care; re-admission
      rates show promise as an outcome measure which relate to the quality of discharge
      planning and merit further study. In terms of ambulatory care, there is an urgent
      need to develop and evaluate a symptom-based outcome measure which would be
      usable in routine practice and could be recommended for widespread use. As a
      physiological outcome measure, percentage of best function is one which corrects
      for the degree of irreversible air flow obstruction and is independent of
      treatment step. It is valuable for individual patients by providing a realistic
      gold standard and if best function is assessed in a standard manner, it also
      allows results of groups of patients to be compared in a meaningful manner.
      Severity scores, which might allow categorization of patients on the basis of
      characteristics other than current symptoms or therapy, are currently being
      evaluated.

PMID- 8869437
TI  - Psychosocial factors and asthma.

PMID- 8869438
TI  - Recommendations for peak flow monitoring in children. British Thoracic Society.

PMID- 8869439
TI  - The Hering-Breuer reflex in ventilated children.
AB  - The authors tested the hypothesis that, in the paediatric population, the Hering
      Breuer reflex would be provoked by the positive pressure inflation of mechanical
      ventilation (IPPV), and that the strength of the reflex would relate to the
      child's age and compliance of the respiratory system (CRS). During IPPV, changes
      in air flow, volume and airway pressure were recorded simultaneously. From the
      traces, expiratory times and CRS were calculated. The mean expiratory time (Te1)
      prior to each inflation and the mean expiratory time (Te2) immediately following
      an inflation were determined. The presence of the reflex was indicated by Te2
      being longer than Te1, and the strength of the reflex was calculated as the
      difference between Te2 and Te1 expressed as a percentage of Te1. Twenty children
      were studied who had a mean age of 0.7 years (range 0.1-9.8 years). The reflex
      was provoked in 19 of the 20 patients and was not seen in the oldest patient. The
      strength of the reflex varied from 22 to 144% and was inversely related to
      postnatal age significantly (r = -0.73) but not CRS or inflation volume. It is
      concluded that the Hering-Breuer reflex is provoked during IPPV in young
      children; whether, as in neonates, this influences the efficacy of ventilation
      deserves investigation.

PMID- 8869440
TI  - Inhaled nedocromil sodium in symptomatic young children born prematurely.
AB  - The efficacy of a non-steroidal anti-inflammatory agent (nedocromil sodium, NS)
      has been assessed in young children born prematurely who had recurrent
      respiratory symptoms at follow-up. In a randomized, double-blind cross-over
      trial, either two puffs of NS (2 mg puff-1) or placebo were administered three
      times a day via a spacer device and face mask. Fifteen children, median
      gestational age 27 weeks, birthweight 1100 g and postnatal age 12 months were
      studied. The symptom score was lower in the last 2 weeks of the active period
      (median score 26) compared to the run-in period (median score 55) and the last 2
      weeks of the placebo period (median score 50), P < 0.01. The maximum possible
      symptom score for a 2-week period was 210. Compared to the run-in period,
      children required fewer days of bronchodilator therapy in the last 2 weeks of the
      active treatment (P < 0.01), but not in the placebo period. Although results of
      functional residual capacity (FRC) measurements were available on only 13 of the
      15 children, these did demonstrate a significant change in FRC over the active,
      but not the placebo, period. These data suggest that NS is a useful prophylactic
      agent for children born prematurely and who are symptomatic at follow-up.

PMID- 8869441
TI  - Factors affecting oxygen saturation during methacholine challenge in a mixed
      population.
AB  - Bronchial challenge with methacholine or histamine is associated with a reduction
      in arterial oxygen tension, which can be appreciable. In this study, oxygen
      saturation was monitored during methacholine challenge in subjects with and
      without respiratory disease, over a wide age range, in order to identify factors
      predicting a large fall in saturation during the challenge. Two hundred and
      twenty subjects aged 24-86 years were included, comprising 15 healthy adult
      volunteers, and 205 adults from a random sample of the local adult population
      taking part in a survey of bronchial responsiveness. Subjects with ischaemic
      heart disease or baseline FEV1 < 60% predicted were excluded. Methacholine
      challenge was performed by the Newcastle Dosimeter technique; oxygen saturation
      (SaO2) was monitored using a pulse oximeter and finger probe. Of the 220
      subjects, 27% were current smokers and 39.5% were ex-smokers; 26% reported asthma
      or bronchitis. Mean baseline FEV1 was 100% predicted; mean baseline saturation
      was 97%. Mean fall in saturation was 3.2% (range 0-17.5%). Multiple regression
      analysis revealed that fall in saturation during methacholine challenge is
      related to baseline FEV1, baseline SaO2, log of total methacholine dose inhaled,
      and fall in FEV1 during challenge. Change in saturation was not related to
      subject age, smoking history, reported asthma or bronchitis, or the presence of
      respiratory symptoms. Methacholine challenge produces a significant fall in
      oxygen saturation, but this is not greater in subjects who are old or have low
      baseline saturation.

PMID- 8869442
TI  - Increased expression of membrane-associated phospholipase A2 in the lower
      respiratory tract of asymptomatic cigarette smokers.
AB  - Group II phospholipase A2 (membrane-associated phospholipase A2, M-PLA2)
      hydrolyses the 2-acyl position of a glycerophospholipid. The concentrations of M
      PLA2 in serum and bronchoalveolar lavage fluid (BALF) were measured in 13
      asymptomatic cigarette smokers without clinically detectable lung disease, and
      the results were compared with those in 13 healthy non-smokers, using a specific
      radioimmunoassay. In addition, Northern blot analysis of M-PLA2 mRNA was
      performed in preparations of total RNA extracted from the cell pellet of BALF
      from two smokers and two non-smokers. No significant difference was found in
      serum M-PLA2 levels between 13 smokers (mean +/- SD, 3.48 +/- 1.21 ng ml-1) and
      13 non-smokers (3.12 +/- 1.06 ng ml-1). The smokers' BALFs contained
      significantly greater levels of M-PLA2 compared with the non-smokers', whether
      expressed in terms of BALF volume (0.59 +/- 0.34 vs. 0.12 +/- 0.09 ng ml-1, P <
      0.001) or protein content (7.22 +/- 3.17 vs. 2.31 +/- 1.48 ng mg-1 protein, P <
      0.001). Northern analysis showed that the levels of M-PLA2 mRNA in two smokers
      were greater than those in two non-smokers. Thus, cigarette smoking was
      associated with increased levels of M-PLA2 in BALF. This enzyme may be involved
      in the pathogenesis of pulmonary disease associated with cigarette smoking.

PMID- 8869443
TI  - Comparison of males and females presenting with acute asthma to the emergency
      department.
AB  - OBJECTIVES: To determine the female:male ratio and compare the severity of asthma
      between female and male patients presenting with acute asthma to the authors'
      emergency department (ED). PATIENTS: Patients aged 15-50 years presenting with
      acute asthma. SETTING: Emergency department of a university-affiliated hospital.
      METHODS: Retrospective analysis of asthma surveillance data and medical records
      of all asthma-related visits to ED over 6 months (January 1992-June 1992).
      RESULTS: One hundred and thirty-seven patients aged 15-50 years made 196
      consecutive visits to the authors' ED over 6 months. The ratio of female:male
      patients was 1.9 and the ratio of the number of visits made by female vs. male
      patients was 2.6. Initial peak expiratory flow rate (PEFR) and forced expiratory
      volume in 1 s (FEV1) were recorded in 94% and 49% of the visits, respectively.
      There was no statistically significant difference between the male and female
      patients in heart rate, respiratory rate or percentage of patients admitted to
      hospital. The mean (SD) initial FEV1 as a percentage of predicted was
      significantly higher in females compared to males (49% +/- 20% vs. 33% +/- 15%; P
      < 0.001). CONCLUSION: In the authors' institution there is a high female:male
      ratio among patients presenting with acute asthma, and males tend to present
      later or with more severe disease. These findings need to be confirmed by a
      prospective study looking at all the factors that may contribute to asthma
      patients presenting to the ED.

PMID- 8869444
TI  - Pulmonary function of patients with spontaneous pneumothorax in relation to the
      extent of emphysema-like changes.
AB  - The aim of the present study was to analyse pulmonary function parameters of
      patients with spontaneous pneumothorax (SP) in relation to the extent of
      emphysema-like changes (ELCs). Pulmonary function tests were performed in 85
      patients with unilateral SP, 6 weeks after video-assisted thoracoscopy (VAT). In
      63 patients, thoracic computer tomography (CT) was obtained. An ELCs score, based
      on findings of CT and VAT, was used to quantify ELCs, ranging from 0 (expressing
      no ELCs) to 3 (expressing extensive ELCs). Emphysema-like changes were detected
      during VAT in 74% of patients, of which 70% were considered larger than 2 cm. An
      ELCs score > or = 2 was found in 27 patients. Clinical characteristics of the
      patients grouped according to thoracoscopical findings and ELCs score did not
      differ, except for age. Patients with large ELCs were significantly older than
      patients without ELCs or small ELCs (P = 0.0009). In patients with large ELCs and
      ELCs score > or = 2, increased mean percentages of predicted total lung capacity
      and decreased diffusing capacity (KCO) were found. None of the patients exhibited
      all pulmonary function criteria of emphysema, in contrast to 43% of the patients
      with an ELCs score > or = 2. KCO was the only pulmonary function parameter which
      was decreased in smokers, especially in patients with large ELCs or ELCs score >
      or = 2. Static lung compliance (Cstat) was the only pulmonary function parameter
      which was increased in patients with recurrent SP. The authors concluded that KCO
      is related to smoking behaviour and ELCs in patients with SP. Cstat is the only
      parameter which is increased in patients with recurrent SP. The discrepancy
      between pulmonary function and macroscopical parenchymal changes could be
      explained by the fact that not all patients with SP are old enough at
      presentation to show all signs of emphysema with pulmonary function testing. On
      the other hand, it might be possible that ELCs in SP cause different pulmonary
      function abnormalities than in centriacinar or panacinar emphysema.

PMID- 8869445
TI  - A combination with clinical recommended dosages of salmeterol and ipratropium is
      not more effective than salmeterol alone in patients with chronic obstructive
      pulmonary disease.

PMID- 8869446
TI  - Intrapleural corticosteroid injection therapy for post-traumatic eosinophilic
      pleural effusion.

PMID- 8869447
TI  - Evidence for marked eosinophil degranulation in a case of eosinophilic pneumonia.

PMID- 8869448
TI  - A recurrent case of spontaneous mediastinal emphysema.
AB  - The first case of spontaneous mediastinal emphysema was reported by Hamman et al.
      in 1939. It is a rare condition that primarily occurs in young adults. In many
      instances, spontaneous mediastinal emphysema is caused by yelling, shouting or
      active exercise, but the cause is often unknown. It is rare for cases of
      spontaneous mediastinal emphysema to recur. Recently, we experienced a recurrent
      case of spontaneous mediastinal emphysema in a patient with a duodenal ulcer.
      Vomiting appeared to be the cause of the recurrence in our patient. Of the 58
      patients with spontaneous mediastinal emphysema who have been reported in Japan
      so far, recurrences were documented only in our patient and two others.

PMID- 8869449
TI  - Effectiveness of bovine gallstone (Goou) and bear gall powder (Yutan) on chronic
      liver diseases: a preliminary report.
AB  - The author reports 23 cases of chronic liver disease which showed remarkable
      improvement with the administration of bovine gallstone (Goou) and bear gall
      powder (Yutan). The concomitant administration of both Goou at 200 mg/day and
      Yutan at 60 mg/day resulted in marked improvement of liver function as well as
      subjective complaints in all the patients within one month. The administration of
      Goou alone was also effective, but concomitant administration of Goou and Yutan
      tended to be more effective than administration of Goou alone in cases of liver
      cirrhosis. These results suggest that animal crude drugs (Goou and Yutan) are
      reliable medicines for intractable chronic liver diseases.

PMID- 8869451
TI  - Histochemical demonstration of acid phosphatase in a human retinal pigment
      epithelial cell line.
AB  - The retinal pigment epithelium (RPE) has numerous lysosomes and shows the highest
      acid phosphatase activity among eye tissues. In an established cell line of human
      RPE (K-1034), acid phosphatase activity, as a lysosome marker was investigated
      histochemically to evaluate the maintenance of original RPE characteristics. Even
      after 100 passages, RPE cells showed remarkable enzyme activity, and had numerous
      electron-dense bodies which were confirmed to be lysosomes. These results show
      that this cell line can maintain one of the vital functions of the RPE and
      provide useful experimental material for functional studies of the human RPE.

PMID- 8869450
TI  - Effectiveness of daily living abilities (DLA) as a tool for evaluating vocational
      competencies: study of non-disabled workers aged 45 and over.
AB  - A questionnaire survey was conducted on 28-55 items of daily living abilities
      (DLA) linked to 13 basic vocational competencies such as memory, learning,
      planning, judgement, muscular power and concentration covering a total of 505 non
      disabled blue collar male workers aged 45 and over. Results of the survey were as
      follows, (1) The 457 subjects were grouped into five groups ranging from normal
      to unsound groups according to the degree of DLA; (2) The reduction of DLA has
      directionality to two factors, memory and muscular power; (3) DLA provide clues
      for aging; (4) Among basic vocational competencies, muscular power showed the
      highest performance with a small standard deviation, while concentration scored
      low points with a large standard deviation (p < .05); (5) No age difference was
      found in planning ability, coordination, muscular power, physical tolerance,
      manual dexterity, and sense of equilibrium, while subjects aged 65 or over showed
      significantly low figures for learning ability, agility and concentration (p <
      .05); Since the findings showed various characteristics of vocational
      competencies and the aging process precisely in blue collar workers aged 45 and
      over, we assumed that the DLA survey is one of the alternatives for evaluating
      workers vocational competencies.

PMID- 8869452
TI  - Effect of the proteoglycan (PSK) on lymphocyte subsets in normal rats.
AB  - The effect of the proteoglycan biologic response modifier, PSK, on lymphocyte
      subsets was investigated in normal rats. Six-week-old male SPF Wistar-Imamichi
      rats were fed a diet containing 2% PSK. Peripheral blood lymphocytes (PBL),
      thoracic duct lymphocytes (TDL), and those existing in the thymus, spleen and
      Peyer's patches were collected for analysis of subsets of T cells, helper/inducer
      T (Th) cells, suppressor/cytotoxic T (Ts) cells and B cells compared with those
      of the control group. In the PBL, differential and absolute counts of T and Th
      cells were lower in the group fed PSK (the PSK group) than the control group.
      There was no difference in Ts cells between the groups, and the PSK group showed
      a higher B-cell differential count. In the case of TDL, the PSK group showed
      greater absolute counts of T and Th cells than the control group. In tissue
      lymphocytes, differential T and Th cell counts were significantly greater in the
      PSK group than the control group, as observed first in Peyer's patches and later
      in the spleen. No differences between the groups were observed in these counts in
      the thymus. Changes in body distribution of T and Th cells induced by PSK
      treatment first appeared in lymphocytes in Peyer's patches, followed by PBL and
      TDL, and those in the spleen. No such changes were observed in the thymic
      lymphocytes.

PMID- 8869453
TI  - Hepatic cytokeratin changes in obstructive jaundice: before and after biliary
      drainage.
AB  - We investigated the changes in hepatic cytokeratins in obstructive jaundice by
      immunohistochemistry. The results can be summarized as follows: 1) In accordance
      with the progression of the jaundice, the lobular and cellular distribution of
      cytokeratin reactivity in hepatocytes expanded. 2) Cytokeratin reactivity in
      obstructive jaundice was improved by removal of the bile duct obstruction
      (decompression), but this decompressive effect deteriorated in the case of
      prolonged jaundice. 3) It is suggested that the specific lobular and cellular
      distribution and/or the changes in cytokeratin aggregation might be of value in
      determining the stage and in predicting the prognosis of obstructive jaundice.

PMID- 8869454
TI  - Urinary concentrations of heavy metals in healthy Japanese under 20 years of age:
      a comparison between concentrations expressed in terms of creatinine and of
      selenium.
AB  - Voided urine samples from 575 young Japanese under 20 years of age (297 males and
      278 females including infants) and from 380 subjects (20-29 years old, 193 males
      and 187 females) were analyzed for levels of creatinine, selenium, zinc, cadmium
      and mercury. This investigation presents data regarding the normal urinary levels
      of these substances in age groups of 0-4, 5-9, 10-14, 15-19, and 20-29 years.
      Urinary levels of creatinine and cadmium showed remarkable increases with the age
      of the subjects, whereas that of selenium was constant at all ages under 20.
      Urinary concentrations of heavy metals were represented by creatinine and
      selenium ratios. Comparisons between these ratios revealed that selenium is an
      excellent index for representing the levels of the substances contained in a
      voided urine sample. Creatinine was not useful as an index for younger subjects,
      because the urinary concentration of this compound increased almost threefold as
      the subjects became older, up to 15 years of age.

PMID- 8869455
TI  - Intravenous administration of vancomycin is ineffective against bacteremia
      following tooth extraction.
AB  - The incidence of transient bacteremia after tooth extraction without
      antimicrobial prophylaxis has been reported was high as 69.2%; that with
      intravenous ampicillin as 4.2% (1, 2). Currently, we tested a regime of
      vancomycin that was recommended by the American Heart Association as prophylaxis
      for oral surgery patients who were allergic to penicillin and evaluated its
      effectiveness. Before the surgical procedures, we started an intravenous drip
      infusion of vancomycin. Ten of 26 patients became blood culture positive (38.5%).
      Seventeen strains of bacteria were isolated. The Minimum Inhibitory
      Concentrations (MICs) of vancomycin were lower than 3.13 micrograms/ml, with just
      one exception.

PMID- 8869456
TI  - Opioid therapy for chronic nonmalignant pain: a review of the critical issues.
AB  - The controversy surrounding the long-term use of opioid drugs in patients with
      nonmalignant pain has intensified in recent years. This debate is driven by a new
      willingness to consider the potential benefits of an approach that has been
      traditionally rejected as invariably ineffective and unsafe. The published
      literature continues to be very limited, but a growing clinical experience,
      combined with a critical reevaluation of issues related to efficacy, safety, and
      addiction or abuse, suggests that there is a subpopulation of patients with
      chronic pain that can achieve sustained partial analgesia from opioid therapy
      without the occurrence of intolerable side effects or the development of aberrant
      drug-related behaviors. Future research must confirm this impression through
      controlled clinical trials and clarify those factors that may predict therapeutic
      success or failure. For the present, the clinician who contemplates this approach
      must have a clear grasp of the relevant issues and an understanding of the
      guidelines for treatment and monitoring that have proved useful in practice.

PMID- 8869457
TI  - Clinicians' attitudes about prolonged use of opioids and the issue of patient
      heterogeneity.
AB  - Despite advances in medical knowledge, sophisticated imaging procedures, and
      treatment approaches, a significant number of chronic pain patients continue to
      suffer from unremitting pain. Recently, it has been suggested that opioid
      analgesics should be used more extensively with this population. This suggestion
      has resulted in considerable controversy. The preliminary research upon which
      opioid use for chronic pain patients is based is reviewed and demonstrated to be
      equivocal. The results of two recent surveys that have addressed physicians'
      attitudes and prescribing practices for chronic pain patients are discussed.
      Proposed guidelines for prescribing opioids for chronic pain patients are
      examined.

PMID- 8869458
TI  - Comprehensive pretreatment and outcome assessment for chronic opioid therapy in
      nonmalignant pain.
AB  - Guidelines currently exist on the use of opioid therapy for chronic nonmalignant
      pain. Unfortunately, no randomized, prospective, controlled studies have been
      conducted to verify these guidelines or determine the optimal inclusion or
      exclusion criteria for this treatment. The decision to administer opioid therapy
      is often based on treatment orientation and subjective clinical impressions. This
      article contains two sections relevant to assessment for chronic opioid therapy
      in nonmalignant pain. First, a brief review of the literature on opioid therapy
      is presented. Survey data on opioid use and follow-up helpfulness are also
      presented. Second, current guidelines for opioid therapy are discussed, and areas
      considered critical in assessing treatment efficacy are reviewed, including (1)
      pain intensity, (2) functional capacity, (3) personality and mood, (4) pain
      beliefs, (5) medication usage, (6) adverse effects, (7) health-care utilization,
      and (8) medical and psychosocial history. Finally, questions are posed for future
      investigations of the efficacy of opioid therapy in selected patients with
      chronic nonmalignant pain. This article identifies important areas to consider
      when initiating controlled trials designed to identify those patients most
      suitable for chronic use of opioids.

PMID- 8869459
TI  - Patient satisfaction and pain severity as outcomes in pain management: a
      longitudinal view of one setting's experience.
AB  - Longitudinal data from quality assurance studies of pain outcomes (pain severity
      and patient satisfaction) were critically examined to explore the reasons that
      patients are satisfied with their care even when they are in pain. Data were
      acquired from three sources: self-report surveys of patients during inpatient
      admission or ambulatory clinic visit (N = 306), telephone interviews of patients
      after discharge (N = 869), and chart reviews (N = 112). These data were compared
      to baseline data obtained 2 years ago, before the implementation of a number of
      programs designed to improve pain management. Findings reveal little change from
      baseline with respect to patient satisfaction with pain management--an
      overwhelming percentage are satisfied or highly satisfied. Similarly, there has
      been little change in pain intensity ratings--on average, patients' worst pain is
      approximately 7 on a 0-10 scale. In addition, almost all analgesic orders
      continue to be written for "as needed" administration. Based on these findings,
      we postulate that patients are satisfied even though they are in pain because
      they experience a commonly expected peak and trough pattern of pain relief, a
      pattern that occurs with "as needed" administration. That is, we conclude that
      pattern of pain relief, not pain severity, may be the critical determinant of
      satisfaction.

PMID- 8869460
TI  - Critical pathways: a road to institutionalizing pain management.
AB  - Effective strategies to increase the visibility of pain and the accountability of
      health-care professionals for the treatment of pain are needed to improve the
      quality of pain management. Critical pathways are tools used to plan and document
      care for patients within a system of case management. Case management models of
      care focus on decreased cost, better coordination of services, and improved
      patient outcomes. This article describes how critical pathways are being used in
      one setting within a system of case management to help increase awareness of pain
      as a problem and to institutionalize pain management. As institutions seek to
      implement outcome-based practice systems, many are turning to the critical
      pathway to influence practice patterns. Critical pathways provide the vehicle to
      articulate and implement a standard for quality pain management and a mechanism
      to analyze persistent failures in achieving desired outcomes of care. Using
      pathways to track and monitor care promises to uncover clinical barriers to pain
      management and provide an impetus to increase clinician accountability for pain
      relief.

PMID- 8869461
TI  - Epidemiology of inhibitors in haemophilia A.
AB  - One of the most serious complications of the treatment of haemophilia A is the
      development of inhibitors. Former studies mostly considered the prevalence of
      inhibitor development, thus underestimating its true risk. Prevalences ranged
      widely (7-18%) probably due to the populations studied and the study design.
      Recent prospective previously untreated patients (PUP) studies were more
      comparable because of similar study designs. Eight PUP studies regarding the
      incidence of factor VIII inhibitors were analyzed: The inhibitor incidences
      (Independent of severity of haemophilia) ranged from 18.4 to 28%. Evaluating only
      severe haemophiliacs (factor VIII < 2%) significantly higher incidences were
      found. After 9-36 exposure days (as medians inhibitor development occurred at 0.8
      3.3 years of age (as medians).

PMID- 8869462
TI  - Human anti-factor VIII antibodies: epitope localization and inhibitory function.
AB  - Recombinant polypeptides derived from coagulation factor VIII (fVIII) have been
      used to determine the epitopes and characteristics of human pathologic anti-fVIII
      antibodies. The results of immunoprecipitation assays indicate that 70% of
      patient plasmas contain antibodies to the A2 as well as the C2 domains of the
      fVIII protein. The same polypeptides were used for inhibitor neutralization
      assays to demonstrate that about 60% of plasmas contain 2 or 3 different
      antibodies which collectively make up the inhibitor titer. The results of
      neutralization assays indicate that there is a third important inhibitor epitope
      within the light chain outside C2. Anti-A2 antibodies prevent normal function of
      the factor Xase complex of the intrinsic pathway of blood coagulation. Anti-C2
      antibodies prevent the binding of fVIII to phospholipid and to von Willebrand
      factor, both of which are important for normal fVIII function.

PMID- 8869464
TI  - The treatment of factor VIII inhibitors--a general overview.
AB  - The management of patients with classic hemophilia who develop inhibitory
      antibodies against transfused factor VIII has been the frequent subject of
      international and national conferences. While treatment of such patients cannot
      be considered as standardized, several therapeutic approaches are currently
      available. These include the induction of immune tolerance, removal or
      eradication of inhibitory antibodies by immune adsorption and/or immune
      suppression, neutralization of the inhibitor by porcine factor VIII or high doses
      of human factor VIII, and bypassing of the inhibitor using recombinant factor
      VIIa or other bypassing agents. In addition to currently available therapeutic
      strategies, other approaches are under investigation, including the use of
      selected factor VIII peptides that block the inhibitor; the use of
      immunologically mute factor VIII products, for example a human-porcine factor
      VIII chimera not recognized by factor VIII inhibitors, and the use of anti
      idiotypic antibodies. The ability to recognize those patients destined to develop
      inhibitors is also under active investigation.

PMID- 8869465
TI  - Delineating physiological (natural) autoreactivity from pathological
      autoimmunity.

PMID- 8869463
TI  - Variations in antigenicity of factor VIII concentrates: preclinical evaluation.

PMID- 8869466
TI  - Immune tolerance for the treatment of factor VIII inhibitors--twenty years' 'bonn
      protocol'.

PMID- 8869467
TI  - Immune tolerance and the immune modulation protocol.

PMID- 8869468
TI  - The international registry of immune tolerance: 1994 update.

PMID- 8869469
TI  - Induction of immune tolerance, the future of the Registry.
AB  - Factor VIII (FVIII) inhibitors are IgG antibodies that neutralize the
      procoagulant activity of FVIII, rendering hemorrhages difficult to manage. There
      may exist a genetic predisposition with consequent imbalance of T and B cell
      function. Efforts at inhibitor eradication in the last 20 years have produced a
      multitude of immune tolerance induction (IIT) protocols with variable outcome.
      Data derived from the International Registry indicate that inhibitor titer at
      outset of IIT and dose of FVIII concentrate used are important predictors of
      success. Future Registry activities should identify optimally standardized IIT
      regimens designed on the basis of patient likelihood to achieve tolerance and
      should provide further understanding of T and B cell interaction in the treatment
      process.

PMID- 8869470
TI  - Immunological and laboratory aspects of immune tolerance.

PMID- 8869471
TI  - Protocols, dosages and clinical aspects of immune tolerance.

PMID- 8869472
TI  - Low-dose immune tolerance therapy: the van creveld model.

PMID- 8869473
TI  - Induction of tolerance using porcine factor VIII.

PMID- 8869474
TI  - Immune tolerance: a nursing perspective.

PMID- 8869475
TI  - Immune tolerance in two high responder, severe hemophilia A patients with
      inhibitors: the importance of high doses and the duration of the treatment.

PMID- 8869476
TI  - The economics of immune tolerance and treatment of hemophiliacs with inhibitors.

PMID- 8869477
TI  - Inhibitors to coagulation: can we afford immune tolerance induction regimens?

PMID- 8869478
TI  - Computerization of Fujimori's method of waveform recognition. A review and
      methodological considerations for its application to all-night sleep EEG.
AB  - This article critically reviews 8 computer implementations of Fujimori's method
      for EEG waveform recognition, with methodological considerations for the
      application of this method to the analysis of all-night sleep EEG. Fujimori's
      method has been considered one of the most appropriate waveform analyses for EEG.
      This kind of analysis is advantageous for measuring frequency and amplitude of
      each EEG wave separately. However, current implementations have drawbacks which
      must be resolved before they can be used on all-night sleep EEG. An optimal
      sampling rate should be determined which is appropriate to the purpose of
      analysis. Amplitude thresholds for wave recognition, which are now set
      arbitrarily, should also be improved. Measurement of waves in higher orders of
      superimposition is also necessary, although existing systems are limited to the
      second order. Additional algorithms, such as for the separate detection of sleep
      slow waves, may be useful. Further applications for Fujimori's method are
      suggested.

PMID- 8869479
TI  - Dispersion and culture of magnocellular neurons from the supraoptic nucleus of
      the adult rat.
AB  - A simple and efficient procedure for the dispersion and culture of magnocellular
      neurons of the adult rat hypothalamus was developed. The enzymatically and
      mechanically dispersed cells were highly viable and showed neurite outgrowth
      after 3 days of culture. The neurons could be maintained for more than 4 weeks
      without any sign of deterioration. Light-optic immunocytochemistry of the
      cultured cells revealed the presence of many oxytocin- and vasopressin
      immunoreactive neurons. The results indicate that the method may be suitable for
      many experimental purposes.

PMID- 8869480
TI  - Proximal branching patterns of middle cerebral artery (MCA) in rats and their
      influence on the infarct size produced by MCA occlusion.
AB  - The branching patterns of the proximal middle cerebral artery (MCA) and their
      influence on the infarct size following MCA occlusion in rats were studied. In
      the proximal part from the level of the olfactory tract, the MCA most often
      presented one surface branch extending anteriorly, with a variable number of
      surface branches extending posteriorly. We classified the branching patterns of
      the posteriorly extending surface branches as follows: Type 1 (57.5%), one
      prominent proximal surface branch; Type 2 (30.2%), no prominent branch but two or
      more small surface branches; and Type 3 (12.3%), no surface branches with a
      visible junction with the MCA but surface branches probably arising from the
      internal carotid artery at the origin of the MCA. When the proximal surface
      branches (especially that in Type 1) remained uncoagulated, the infarct size in
      both the cortex and striatum was significantly reduced compared with that when
      coagulation was proximal to the most proximal surface branch. The reduction of
      cortical and striatal infarct sizes was particularly prominent in the posterior
      portion. To increase the infarct size and reduce variability, it is suggested
      that the MCA trunk should be coagulated from the origin to the rhinal fissure
      including the surface branches.

PMID- 8869481
TI  - Distribution-free graphical and statistical analysis of serial dependence in
      neuronal spike trains.
AB  - Two-dimensional 'joint' interval distributions of sequential interspike (ISIs)
      are a commonly used tool in neuronal spike train analysis. We present and
      evaluate here a modification of the joint interval plot using ranked ISIs. This
      modification provides clearer graphical evaluation of serial dependence in ISI
      sequences, a distribution-free basis for isolating changes in serial dependence
      across experimental treatments from changes in ISI distributions, and a basis for
      unambiguous statistical tests of serial dependence and stationarity. To validate
      this method and illustrate the advantages of its use we have applied it to both
      single-neuron spike trains recorded from cultured mammalian spinal cord neurons
      and artificial spike trains generated by stochastic models with defined burst
      envelopes and serial dependencies.

PMID- 8869482
TI  - A radiotelemetric 2-channel unit for transmission of muscle potentials during
      free flight of the desert locust, Schistocerca gregaria.
AB  - A new radio-telemetric technique for neuroethological investigation of the
      natural behaviour of insects is presented. The 2-channel miniature transmitter
      device allows the transmission of electromyograms of 2 muscles during free flight
      of a locust. The mass of this transmitter and power supply is 0.55 g and can be
      carried by a mature female without marked impairment of the free-flight
      behaviour. The radiated power of the transmitter is approximately 20 nW and is
      sufficient to cover a range of more than 20 m. The carrier-frequency (145 MHz) of
      the system is frequency-modulated by the inputs of the 2 different channels.
      Channel separation is achieved by a multivibrator circuit. The chopping frequency
      (2 kHz) allows a convenient resolution of both signal channels. The design of the
      2-channel transmitter device is presented and tested. Its relevance for the
      studies of natural flight of locusts is given, however, other applications are
      also feasible.

PMID- 8869483
TI  - A reliable and sensitive method for fluorescent photoconversion.
AB  - The objective of this study was to develop a reliable and sensitive method of
      diaminobenzidine (DAB) photoconversion through systematic variation of the
      objectives and the method of DAB enhancement employed. Results showed that
      reliable photoconversion of DiI-labeled macaque monkey cortical cells and
      processes can be obtained consistently by using fresh filtered DAB solutions,
      clean slides, and a bright fluorescent light source. Using a 20x objective and
      enhancing the DAB reaction product with Giemsa stain provided the most
      sensitivity and best resolution in the photoconverted area. Objective size was
      found to correlate directly with sensitivity and indirectly with both the size of
      the area photoconverted and the time to complete photoconversion. Nitro blue
      tetrazolium (NBT) did not produce as much contrast in the photoconverted cells as
      Giemsa stain, but allowed for the best visualization of finer processes because
      it somewhat enlarged the fiber diameter. Nickel and cobalt used together, but not
      separately, were found to provide adequate enhancement. These results are likely
      to apply to photoconversion and enhancement of all fluorescent material, but may
      require slight modifications in protocol.

PMID- 8869484
TI  - Stimulus artifact removal in EMG from muscles adjacent to stimulated muscles.
AB  - When stimulating muscles, EMG signals recorded in neighboring muscles can be
      contaminated by stimulus artifacts, and artifact deletion is necessary. We have
      devised a digital technique for removing stimulus artifacts from rectified EMG
      recordings in muscles which lie close to a stimulated muscle. This artifact
      deletion method replaces the rectified EMG during the artifact interval with an
      estimate of the rectified EMG. Our research requires detection of very small
      changes in EMG levels. Therefore, the artifact deletion technique described in
      this paper was designed to leave less than 10 microV of artifact in the rectified
      EMG post-processing. This technique relies on being able to estimate the artifact
      duration. Since stimulated muscles have M-waves that can overlap with artifacts,
      our technique is only appropriate for removing artifacts in muscles which are not
      being stimulated. Unlike other artifact elimination techniques, our technique
      does not change the mean value of the rectified EMG, regardless of artifact
      width. In addition, it provides a more accurate estimate of the rectified EMG
      during the artifact interval as opposed to sample-and-hold techniques.

PMID- 8869485
TI  - A modified method of estimating phase resetting of rhythmical movement.
AB  - A computer-based method of estimating resetting index is presented which was
      successfully applied to a study of resetting of human voluntary rhythmical
      movement. Peaks were detected before and after the stimulus (magnetic cortical
      stimulation) from position records and the phase of stimulation and the phase
      change induced by the stimulus estimated. The phase change versus phase of
      stimulation relationship was rotated until the best linear fit was obtained: the
      gradient of this relationship is the resetting index. The calculation of
      resetting index was thus independent of the initial assignment of reference
      phase. A constant, the null phase, was derived from the best linear fit and
      indicates the phase to which the original waveform is being reset by the
      stimulus. Statistical tests of significance and linearity of the final
      relationship are also described.

PMID- 8869487
TI  - Marking microelectrode penetrations with fluorescent dyes.
AB  - Fluorescent dyes were used to mark and identify the tracks left by extracellular
      microelectrodes in neurophysiological experiments. Forty-two penetrations were
      made into the postcentral gyrus of 3 Macaque monkeys with electrodes coated with
      1 of 5 fluorescent dyes (DiI, DiO, DiI-C5, PyPO, and Fast Blue). The electrodes
      were driven at rates ranging from 10 to 1000 microns/min, to a depth of about
      4000 microns, where a small electrolytic lesion was made. Histological sections
      were viewed under fluorescent optics and the electrode tracks were reconstructed
      from the dye traces. Fluorescent traces (width 50-400 microns) were observed in
      41 of 42 penetrations with 24 traces extending to the lesion site. Of the
      electrodes driven in less than 3 h, those coated with DiI (8/8) and DiI-C5 (8/8)
      left a trace to the lesion site, while 57% (4/7) of the DiO, 40% (2/5) of the
      Fast Blue and only 11% (1/9) of the PyPO tracks were fully marked. This method of
      marking penetrations can be used with any extracellular recording configuration,
      does not require tissue sections to be processed or stained, does not require
      electrical lesions, and causes no detectable tissue damage. Because the dyes
      fluoresce at different wavelengths, closely spaced tracks can be uniquely
      identified.

PMID- 8869486
TI  - Postembedding immunocytochemistry of large sections of brain tissue: an improved
      flat-embedding technique.
AB  - A method for osmicating, dehydrating, and flat-embedding large slabs of brain
      tissue in epoxy resin is presented. This permits the production of semithin
      sections for postembedding immunocytochemistry that are far larger than can be
      obtained with other embedding approaches. Vibratomed slabs, 50-200 microns thick
      and as large as 6 x 8 mm are embedded in a 'soft' Araldite epoxy. The slabs are
      laminated onto the flat surface of a pre-cast epoxy slide. After polymerization,
      the tissue can be studied on the slide as a whole mount to view osmicated fiber
      tracts, or in experimental tract-tracing studies, to locate retrogradely labeled
      cells before semithin sections are cut. The rigidity of the epoxy slide ensures
      that the slabs remain flat and are easily removed and mounted for resectioning.
      Semithin sections are cut using 8 mm wide glass knives or a 6 mm wide diamond
      knife and are mounted singly or in serial pairs and immunostained using
      conventional etching and immunoperoxidase techniques. The relative softness of
      the epoxy permits dozens of semithin sections to be cut from large blocks without
      appreciably degrading a glass knife edge. After further polymerization the
      embedment is also compatible with electron microscopy.

PMID- 8869488
TI  - Anatomical and immunohistochemical identification of catecholaminergic neurones
      in brain slice preparations used in electrophysiology.
AB  - The physiological characteristics of central neural populations are being
      increasingly explored in slice preparations. A major challenge of this approach
      is to correlate the physiological properties of individual neurones or groups of
      neurones with their anatomical and chemical properties in order to gain key
      insights into their functional identities. The present study describes a method
      for determining the precise topographical position and the immunohistochemical
      characteristics of neurones in brain slice preparations that are used frequently
      in electrophysiological investigations. Thick horizontal slices of rat brainstem
      were re-cut using a method that provided thin sections that were always in the
      same plane as the parent slice and that were of suitable thickness for
      immunohistochemistry. Catecholaminergic neurones in these co-planar (horizontal)
      sections were stained using antisera to tyrosine hydroxylase, the rate-limiting
      enzyme for catecholamine synthesis. To identify individual catecholamine neurones
      in the co-planar sections, we constructed a reference atlas of the distribution
      of catecholamine neurones in the horizontal plane of the rat brain. The combined
      use of the horizontal atlas and of immunohistochemical techniques in co-planar
      sections of horizontal slices enables the determination of several key
      properties: (1) whether a neurone is TH-positive, (2) its precise topographical
      position and (3) its content of neuropeptides and other immunohistochemical
      markers. Thus our study offers a readily feasible method for correlative anatomy
      and immunohistochemistry of physiologically identified catecholaminergic neurones
      in brain slices.

PMID- 8869489
TI  - Cuff electrodes for chronic stimulation and recording of peripheral nerve
      activity.
AB  - A comparative study of 5 different designs of nerve cuff electrodes was
      undertaken to determine their relative merits for stimulating and recording whole
      nerve activity over extended periods of chronic implantation on large and small
      peripheral nerves in 8 cats. Four of the designs represent novel fabrication
      strategies, including 2 based on flexible, thin-film substrates and 2 based on
      dip-coating silicone elastomer on a cylindrical mandrel. Various advantages and
      shortcomings of these materials and designs are discussed in the context of the
      biophysical factors that influence these electrophysiological interfaces,
      particularly the problem of recording microvolt-level neurograms in the presence
      of millivolt-level electromyograms from adjacent muscles in freely behaving
      subjects. The most effective design was one in which a thin sheath of silicone
      rubber was wrapped around and intra-operatively sealed to a longitudinally slit,
      tripolar cuff made by dip-coating silicone over stranded stainless steel leads
      that were prepositioned on a mandrel using polyvinyl alcohol as a temporary
      adhesive. When properly installed, these electrodes had stable impedances,
      recruitment thresholds and relatively interference-free recording properties for
      the duration of this study (up to 9 weeks).

PMID- 8869490
TI  - A transparent model of the human scala tympani cavity.
AB  - A dimensionally accurate clear model of the human scala tympani has been produced
      to evaluate the insertion and position of clinically applied intracochlear
      electrodes for electrical stimulation. Replicates of the human scala tympani were
      made from low melting point metal alloy (LMA) and from polymethylmeth-acrylate
      (PMMA) resin. The LMA metal casts were embedded in blocks of epoxy and in clear
      silicone rubber. After removal of the metal alloy, a cavity was produced that
      accurately models the human scala tympani. Investment casting molds were made
      from the PMMA scala tympani casts to enable production of multiple LMA casts from
      which identical models were fabricated. Total dimensional distortion of the LMA
      casting process was less than 1% in length and 2% in diameter. The models have
      been successfully integrated into the design process for the iterative
      development of advanced intracochlear electrode arrays at UCSF. These fabrication
      techniques are applicable to a wide range of biomedical design problems that
      require modelling of visually obscured cavities.

PMID- 8869491
TI  - Morphometric dendritic field analysis of pyramidal neurons in the human
      prefrontal cortex: relation to section thickness.
AB  - The 3-dimensional (3D) basal dendritic branching patterns of the layers IIIc and
      V pyramidal neurons in the human prefrontal cortex were morphometrically analyzed
      using Golgi-Cox stained single sections without reconstruction. Since the
      dendritic field extends beyond the section, the section thickness affected its 3D
      measures, such as total dendritic length per neuron. An exploratory analysis to
      assess the cutting effect in relation to section thickness was performed by
      examine the graphic display of the following dendritic measures per section
      thickness class of 10 microns, within a total range of 101-210 microns: (1)
      percentage cut dendritic segments, (2) individual terminal segment length, (3)
      radial distance from the terminal tips, and (4) total dendritic length per
      neuron. Additionally, 1-way analysis of variance (ANOVA) was applied with section
      thickness as main factor. The graphic displays did not show a trend towards
      increasing dendritic lengths and distances with increasing section thickness. In
      general the ANOVA showed no statistically significant effect of section
      thickness, with the exception of one thickness class (layer IIIc: 151-160
      microns). This leads to the conclusion that the thickness range has to be larger
      to detect a cutting effect related to section thickness.

PMID- 8869492
TI  - In situ hybridization for vasopressin mRNA in the human supraoptic and
      paraventricular nucleus; quantitative aspects of formalin-fixed paraffin-embedded
      tissue sections as compared to cryostat sections.
AB  - In order to study the suitability of formalin-fixed paraffin-embedded brain
      tissue for vasopressin (AVP)-mRNA detection, we used symmetric halves of 5 human
      hypothalami. In every case, one half was formalin fixed for 10-35 days and
      paraffin embedded while the other half was frozen rapidly. Following in situ
      hybridization (ISH) histochemistry on systematically obtained sections of the
      supraoptic (SON) and paraventricular nucleus (PVN) of both halves, total amounts
      of AVP-mRNA in these nuclei were estimated using densitometry of film
      autoradiographs. Total amounts of radioactivity were found to vary considerably
      between patients and amounted to 1297 +/- 302 arbitrary units (AU) (PVN) (mean +/
      SEM) and 2539 +/- 346 (SON) for the cryostat sections and 868 +/- 94 (PVN) and
      1259 +/- 126 (SON) for the paraffin tissue. Variations introduced by the method
      itself yielded a coefficient of variation of only 0.19. Furthermore, a non
      significant negative trend with postmortem delay was found in cryostat tissue,
      but not in paraffin sections. No effect of fixation time was observed in the
      paraffin tissue. Both ways of tissue treatment have specific advantages and
      disadvantages that may be different for other probes or other brain areas. For
      ISH of a highly abundant mRNA like AVP in a very heterogeneous brain area such as
      the human hypothalamus, formalin-fixed paraffin-embedded tissue sections can be
      used for quantitative analysis of entire brain nuclei because of the small
      variation in this tissue, the remarkably good signal recovery (some 75% as
      compared to cryostat sections) and its practical advantages with regards to
      anatomical orientation, storage and sampling of the tissue.

PMID- 8869493
TI  - Development and application of a modified monoclonal hybridoma technique for
      isolating monoclonal antibodies to human brain regions.
AB  - We developed a modified monoclonal hybridoma technique that combines two
      conventional methods: a conventional immunosuppression method with
      cyclophosphamide treatment and an in vitro immunization method. This technique is
      advantageous over conventional methodologies because it requires a shorter period
      for immunization of mice and a smaller quantity of antigen, and gives rise to
      antibody-secreting hybridomas with higher efficiency. One monoclonal hybridoma
      line, designated as BG5, was established by this technique after activation of
      lymphocytes with muramyl dipeptide and with the immunogen obtained from human
      entorhinal cortex. Western blot analysis showed a relatively high expression of
      BG5 antigen in human entorhinal cortex. Our results suggest that this hybridoma
      technique may rapidly facilitate the acquisition of brain region-specific
      antibodies. We call this technique 'suppression immunization followed by in vitro
      stimulation procedure' (SOFISTIC).

PMID- 8869494
TI  - An investigation into the use of SDS-PAGE of cell surface extracts and
      proteolytic activity to differentiate Prevotella nigrescens and Prevotella
      intermedia.
AB  - By comparison of the cell surface proteins derived from the outer membrane and
      fibrils from 14 Prevotella intermedia and 19 Prevotella nigrescens strains using
      SDS and analysed by SDS-PAGE, it was possible to distinguish the two species. A
      polypeptide of approx. 21 kDa distinguished P. intermedia strains, whereas two
      polypeptides of approx. 18 and 22 kDa could be used to identify P. nigrescens
      strains. Four other human oral black pigmented bacterial species (Porphyromonas
      gingivalis, Prevotella denticola, Prevotella loescheii and Prevotella
      melaninogenica) did not have the 18-, 21- or 22-kDa polypeptides shown by P.
      intermedia or P. nigrescens. The cell-associated proteolytic activity of eight
      strains of P. intermedia, 14 strains of P. nigrescens and one strain of P.
      gingivalis (W50) was assessed using four chromogenic substrates. The hydrolysis
      of the substrate GPPNA (indicative of dipeptidyl peptidase IV-like activity) and
      SAAPPNA (elastase-like activity) by P. intermedia strains varied from 32 to 114
      units and 0.5 to 12.6 units of activity respectively, where one unit was defined
      as the amount of protease enzyme catalysing the formation of 1 nmol of p
      nitroaniline under experimental conditions. 37.5% (3 of 8) of P. intermedia
      strains hydrolysed SAAPPNA (chymotrypsin-like enzyme activity) with activities of
      between 7 and 12 units. The hydrolysis of GPPNA and SAAAPNA by P. nigrescens
      strains was 32-149 and 3-16 units, respectively. 57% (8 of 14) of P. nigrescens
      strains hydrolysed SAAPPPNA with activities ranging from 3 to 8 units. None of
      the P. intermedia or P. nigrescens strains examined were found to have trypsin
      like enzyme activity (BAPNA hydrolysis). The GPPNA and SAAAPNA hydrolytic
      activity associated with the proteases from Porphyromonas gingivalis W50 was at
      least twice that of P. intermedia and P. nigrescens strains. The similar
      peptidase activities of P. intermedia and P. nigrescens against chromogenic
      substrates cannot be used to differentiate the species, but SDS-PAGE of cell
      surface protein extracts allowed unambiguous speciation between P. intermedia and
      P. nigrescens. This simple technique of cell surface protein analysis can be
      performed in most laboratories and offers a convenient way by which to
      differentiate the two species.

PMID- 8869495
TI  - Characterization of iturin synthetase in the wild-type Bacillus subtilis strain
      producing iturin and in an iturin deficient mutant.
AB  - The multi-enzyme system responsible for the biosynthesis of iturin, an antifungal
      lipopeptide of Bacillus subtilis, was partially purified by chromatography on
      different affigels. In the wild-type strain, two subunits of the iturin
      synthetase (ITs and ITagp) were characterized: ITs activated only L-Ser, one of
      the iturin amino acid components, and ITagp activated L-Asn, D-Asn, L-Gln and L
      Pro, amino acids corresponding to a partial sequence of iturin. In an iturin
      deficient mutant, the activity of the ITagp subunit was modified.

PMID- 8869496
TI  - Suppression of the thermosensitive replication phenotype of the derivative
      plasmid of pI9789::Tn552 in Staphylococcus aureus may involve integration of the
      plasmid into the host chromosome.
AB  - Plasmid-chromosome co-integration was found to be the mechanism of choice to
      overcome thermosensitivity of replication of the plasmid pS1 in PS80d and RN4220
      strains of Staphylococcus aureus. The integration of the plasmid was sometimes
      accompanied by deletion of a specific section of the plasmid pS1 in PS80d. Growth
      of bacteriophage on strains containing the integrated plasmid and the subsequent
      use of the phage in transduction gave transductants containing plasmids that had
      regained their replication thermosensitivity. These plasmids had not acquired any
      detectable chromosomal DNA. The 16-kb EcoRI fragment of the PS80d chromosome that
      hybridizes to pS1 is the target for recombination in many cases, but apparently
      other sites are also used. This fragment contains sequence homologous to parts of
      the transposon Tn552 and it is probable that site-specific recombination is
      involved in the integration. The possible mechanisms for the integrations and the
      deletions are discussed.

PMID- 8869498
TI  - Use of arbitrarily primed polymerase chain reaction to differentiate Trichophyton
      dermatophytes.
AB  - Dermatophytes such as Trichophyton species are common human pathogens, the
      infection of which results in dermatophytosis (also known as ringworm). Several
      laboratory tests are used routinely for the diagnosis of dermatophytosis, but
      they are either slow or lacking specificity. Through examination of genomic DNA
      from Trichophyton dermatophytes and other fungi in arbitrarily primed PCR, it was
      shown that a random primer 5'-ACCCGACCTG-3' produced bands of 4.3 kb, 1.9 kb, 1.7
      kb and 0.7 kb in T. rubrum DNA, bands of 2.5 kb, 1.9 kb and 0.8 kb in T.
      mentagrophytes var. interdigitale and T. mentagrophytes var. mentagrophytes DNA,
      and bands of 2.5 kb, 1.9 kb, 1.5 kb and 0.9 kb in T. tonsurans DNA. This primer
      amplified bands of different sizes in other fungal DNA. Therefore, based on the
      distinct band patterns observed in arbitrarily primed PCR using this primer, T.
      rubrum, T. mentagrophytes and T. tonsurans dermatophytes could be rapidly
      differentiated.

PMID- 8869497
TI  - Isolation of nifH and part of nifD by modified capture polymerase chain reaction
      from a natural population of the marine cyanobacterium Trichodesmium sp.
AB  - A modified capture polymerase chain reaction (CPCR) technique was used to isolate
      the entire sequence of the nifH gene and its flanking regions from a natural
      population of Trichodesmium sp. A set of specific CPCR primers derived from a
      known 72-bp DNA segment of the nifH sequence permitted isolation of both the
      upstream and the downstream region of Trichodesmium sp. nifH. The 882-bp nifH
      gene presented here is the first full-length gene isolated from Trichodesmium sp.
      A sequence similar to a nif-like promoter was found in front of nifH. The nifH
      open reading frame of Trichodesmium sp. encoded 294 amino acids. Comparative
      analysis of the Trichodesmium sp. NifH sequence revealed strong similarity with
      23 known NifH proteins. Amino acids postulated to be involved in binding of the
      4Fe:4S cluster and those subjected to ADP-ribosylation were present. An open
      reading frame for the nifD gene was identified 189 bp downstream of nifH. A
      sequence similar to the consensus of the nif-like promoter was also found in
      front of nifD.

PMID- 8869499
TI  - Permeability of dormant spores of Bacillus subtilis to gramicidin S.
AB  - Gramicidin S, dissolved in ethanol, penetrated into the inside of the dormant
      spores of Bacillus subtilis, had a partial inhibitory effect on L-alanine
      initiated germination and completely inhibited their outgrowth and vegetative
      growth. The activity of particulate NADH oxidase of the antibiotic-treated
      dormant spores was also influenced significantly. Abnormal morphological changes
      were observed in germinated spores from gramicidin S-treated dormant spores. An
      immunoelectron microscopy method with colloidal gold-IgG complex showed that the
      penetration site of gramicidin S inside dormant spores was mainly the core
      region. These facts suggest that gramicidin S induces the damage of not only the
      outer membrane-spore coat complex but also the inner membrane surrounding the
      spore protoplast, and is able to penetrate into the core region of B. subtilis
      dormant spores.

PMID- 8869500
TI  - Divergicin 750, a novel bacteriocin produced by Carnobacterium divergens 750.
AB  - Divergicin 750, a bacteriocin produced by Carnobacterium divergens 750,
      preferentially inhibited the growth of strains of Carnobacterium and
      Enterococcus. Selected strains of Listeria monocytogenes and Clostridium
      perfringens were also inhibited. The bacteriocin was purified to homogeneity by
      ammonium sulfate precipitation and sequential S-Sepharose, hydrophobic
      interaction and reversed phase chromatography. The complete amino acid sequence
      was determined by Edman degradation. The peptide consisted of 34 amino acid
      residues. The calculated M(r) from the peptide sequence, 3447.7, agreed well with
      that obtained by mass spectrometry. Divergicin 750 did not show any sequence
      similarities to other known bacteriocins. The plasmid-located structural gene
      encoding divergicin 750 (dvn750) was cloned and sequenced. The gene encoded a
      primary translation product of 63 amino acids with a deduced M(r) = 6789.4 which
      is cleaved between amino acid residues 29 and 30 to yield the mature bacteriocin.

PMID- 8869501
TI  - Virulence-associated characteristics and phage lysogenicity of two
      morphologically distinct colonies of Vibrio cholerae O139 serogroup.
AB  - The presence of a temperate phage was demonstrated in a strain of Vibrio cholerae
      O139 isolated from a patient. Spontaneous variants with translucent colonies had
      lost this phage. The loss of the phage was associated with increased
      hydrophobicity, indicating the loss of the capsule. These clones were sensitive
      to serum bactericidal activity, showed decreased expression of such presumed
      virulence factors as proteases, motility and mannose-sensitive pili. Furthermore,
      excision of the phage made the strain dependent on purines for growth.

PMID- 8869502
TI  - Differentiation of intestinal spirochaetes by multilocus enzyme electrophoresis
      analysis and 16S rRNA sequence comparisons.
AB  - Multilocus enzyme electrophoresis (MEE) analysis and comparisons of nearly
      complete 16S rRNA gene sequences (1416 nucleotide positions) were used to
      evaluate phylogenetic relationships among Serpulina hyodysenteriae strain B78T,
      S. innocens strain B256T, Brachyspira aalborgi strain 513AT, and eight
      uncharacterised strains of swine, avian, and human intestinal spirochaetes. From
      MEE analysis, nine strains could be assigned to five groups containing other
      intestinal spirochaetes (genetic distances between groups = 0.6-0.9). Chicken
      spirochaete strain C1 and B. aalborgi 513AT represented unique electrophoretic
      types and formed their own MEE groups. Despite MEE differences, the 11 strains
      had highly similar (96.3-99.9%) 16S rRNA sequences. These findings point out
      limitations of both MEE analysis and 16S rRNA sequence comparisons when used as
      solitary techniques for classifying intestinal spirochaetes related to
      Brachyspira/Serpulina species.

PMID- 8869503
TI  - Resuscitation of Vibrio cholerae O1 strain TSI-4 from a viable but nonculturable
      state by heat shock.
AB  - Vibrio cholerae strain TSI-4 was incubated in an M9 salt solution at 15 degrees C
      for more than 100 days. The plate counts showed no viable cells on day 30, but a
      broth culture from that day showed the growth of bacteria. However, after 35 days
      the bacteria entered the nonculturable state, based on the assessment of both the
      plate counts and broth culture. A portion of the culture was heated at 45 degrees
      C for 1 min in a water bath and subsequently plated onto a nutrient agar plate.
      More than 1000 colonies were recovered after this heat-shock treatment. The
      recovered cells showed the same chromosomal DNA pattern in the restriction map
      and the same outer membrane protein pattern in SDS-PAGE. Recovery of viable cells
      by heat-shock was achieved in cultures grown on M9 salt but not from cultures
      grown in phosphate-buffered saline. This suggests that the presence of NH4Cl in
      the M9 salt solution may support the growth of the bacteria in a low nutrient
      medium, while also playing an important role in resuscitation.

PMID- 8869504
TI  - Production and characterisation of a monoclonal antibody to Serpulina
      hyodysenteriae.
AB  - A monoclonal antibody (mAb) directed against Serpulina hyodysenteriae, the
      causative agent of swine dysentery, was produced and characterised. The mAb
      (BJL/SH1) reacted in Western blots with a protein with a molecular mass of about
      30 kDa in outer membrane preparations from a range of S. hyodysenteriae isolates
      of different serotypes. It did not react with preparations made from a variety of
      non-S. hyodysenteriae intestinal spirochaetes. Immunogold labelling was used to
      confirm the location of the reactive epitope on the cell outer membrane. The mAb
      agglutinated and produced fluorescence only with strains of S. hyodysenteriae,
      and should prove to be a useful reagent for identification of S. hyodysenteriae.

PMID- 8869505
TI  - Immunochemical characterization of a haemagglutinating antigen of Arcobacter spp.
AB  - The Arcobacter haemagglutinin has been identified by Western immunoblot to be an
      immunogenic protein of about 20 kDa. The haemagglutinating activity is sensitive
      to proteolytic enzyme digestion and heat treatment of 80 degrees C and above. The
      Arcobacter haemagglutinin is possibly a lectin-like molecule binding to
      erythrocytes via a glycan receptor containing D-galactose as part of its
      structure.

PMID- 8869506
TI  - Identification of sodC encoding periplasmic [Cu,Zn]-superoxide dismutase in
      Salmonella.
AB  - sodC, encoding [Cu,Zn]-cofactored superoxide dismutase, once thought to be
      virtually confined to eukaryotes, has now been described in many Gram-negative
      pathogens that have their primary niche of colonization in the upper respiratory
      tract. Their role in host-parasite interactive biology is unknown. We here show
      that members of the major human and animal enteric pathogenic species Salmonella
      harbour a version of sodC most closely resembling that found in Brucella abortus.
      The enzyme it encodes is a novel candidate determinant of virulence in
      Salmonella, an intracellular pathogen potentially exposed to toxic oxygen free
      radicals within its intracellular niche.

PMID- 8869507
TI  - Post-traumatic apallic syndrome following head injury. Part 2: Treatment.
AB  - There is no doubt that vegetative patients need the appropriate medical and
      nursing procedures as well as family involvement, education and counselling.
      Additional structured stimulation programmes are used for the treatment of coma
      and vegetative state. The theoretical foundation is derived from animal studies.
      The relevance of the results for the rehabilitation of head-injured human
      patients remains questionable, because all animal studies involve the use of
      cerebral lesions different from those found in human head-injured patients. The
      studies of human sensory stimulation give more an orientation than a definitive
      statement. Very recently, hypotheses concerning sensory regulation have begun to
      be evaluated. Further investigations are required to provide a more definite
      conclusion.

PMID- 8869508
TI  - Assessment of the functional abilities of the upper limbs in patients with
      neuromuscular diseases.
AB  - This article presents a new test for evaluating the functional state of the upper
      limbs (UL) in patients with neuromuscular diseases (NMD). The test consists of 14
      items which in turn break down into 70 (14 x 5) separate objective assessments of
      each patient. The function of proximal muscle groups is determined by the first
      seven test items, and the function of distal muscle groups in the remaining seven
      items. The test was applied to 227 patients with NMD; it has proven valid,
      feasible, acceptable, sensitive and reliable.

PMID- 8869509
TI  - Hearing impairment, disability and handicap in elderly people living in
      residential care and in the community.
AB  - This study aimed to compare the prevalence of hearing impairment, disability and
      handicap in the elderly living in residential care with those living in the
      community, and to examine the relationship between impairment, disability and
      handicap in both groups. Fifty community-based and 129 residential subjects were
      assessed using pure-tone audiometry as a measure of impairment, and a self
      assessment questionnaire as a measure of disability and handicap. Community-based
      subjects were also assessed using a test of speech discrimination as an objective
      measure of disability. Results indicated 95% of residential subjects and 70% of
      community-based subjects were hearing-impaired, while 27% of residential subjects
      and 42% of community-based subjects demonstrated significant disability/handicap.
      Significant correlations were obtained between impairment, disability and
      handicap in both subject groups. The implications of the findings for the aural
      rehabilitation of the elderly are discussed.

PMID- 8869510
TI  - Electrical and mechanical output of the knee muscles during isometric and
      isokinetic activity in stroke and healthy adults.
AB  - Surface electromyography (EMG) and torque were measured from knee flexors and
      extensors in 12 control subjects (CS) aged 25-59 years (10 female) and
      bilaterally in 12 stroke subjects (SS) aged 27-75 years (four female) with
      hemiparesis and mild clinical spasticity. They performed isometric and isokinetic
      maximal voluntary contractions (MVC) and also isokinetic passive movements at
      angular velocities from 30 to 300 degrees/s. The time taken to walk 10 m was
      documented. Greater torque was recorded during passive extension in the paretic
      legs when compared with both non-paretic and control limbs (p < 0.01). No EMG
      activity was measured in any subject. Isometric MVC torque of both muscles in the
      paretic leg was less (p < 0.01) than both the non-paretic and control limbs. The
      SS generated relatively less torque bilaterally at the lower velocities than CS.
      Not all SS reached the higher velocities and none of the paretic limbs achieved
      300 degrees/s during flexion. Gait speed correlated with maximal paretic knee
      extension velocity (p < 0.001). The extent of co-contraction during MVCs was
      generally low or absent and similar in all three groups. These results suggest a
      mechanical rather than reflex cause for the restraint detected clinically. Low
      force generation by the paretic agonists appeared to be the major cause of
      reduced torque, rather than antagonist opposition.

PMID- 8869511
TI  - Activities of daily living studied longitudinally between 70 and 76 years of age.
AB  - Functional performance, i.e. personal and instrumental activities of daily living
      (P-ADL, I-ADL), was studied in a population of 70-year-old persons followed to
      the age of 76, and with an intervention period included between the ages of 70
      and 73. At age 70 (n = 617), 83% were independent, 13% were dependent in I-ADL
      and 4% dependent in I+P-ADL. Among the independent subjects, the 6-year outcome
      in mortality was 13%. Dependence at 70 predicted mortality as well as
      institutionalization, and the risk was higher for those dependent in P+I-ADL than
      for persons dependent in I-ADL only. Of participant survivors the incidence of
      disability was 30% (8% between 70 and 73, 26% between 73 and 76 years of age) and
      was dominated by dependence in I-ADLs. The intervention did not lead to less
      dependence in ADL at age 76. Gender differences were found at age 76 in cooking,
      bathing and dressing, males being more dependent in such activities. At 70, 73
      and 76 years of age, assistance given by relatives dominated.

PMID- 8869512
TI  - What happens to patients awaiting arthritis surgery?
AB  - The length of orthopaedic waiting lists attracts much interest, but the needs of
      patients awaiting surgery gain little attention. We studied 97 patients awaiting
      lower-limb surgery (49 osteoarthritis, 41 rheumatoid arthritis, seven other
      diagnoses). Ninety had pain; 44 significant night pain. Psychological and social
      problems were common (44 and 45 cases respectively). Only 11 were employed full
      time. Sixty-eight required help with daily activities, usually from relatives and
      neighbours. Forty-three patients walked less than 120 metres in 12 minutes. After
      review we recommended further aids in 32, medication changes in 27, and
      additional professional support in six cases. Clinical changes whilst on the
      waiting list caused alterations in the priority for surgery in 32 cases; the
      planned procedure was no longer appropriate in 12 of these. We suggest that
      patients awaiting surgery require clinical review to maintain quality of life;
      and that waiting lists require administrative review so that patients in need of
      surgery receive it as soon as possible.

PMID- 8869513
TI  - Outcomes-based research in neurorehabilitation: the need for multidisciplinary
      team involvement.
AB  - There is a need for the evaluation of neurorehabilitation to reflect the
      integrated multidisciplinary input which is fundamental to the intervention
      process. The importance of multidisciplinary involvement in achieving this is
      discussed with particular reference to multiple sclerosis, which exemplifies the
      many problems inherent in chronic neurological disease that must be addressed in
      the evaluation of the rehabilitation programme. Some of the current difficulties
      of research in this specialty are raised, and suggestions made for the future.

PMID- 8869514
TI  - A diagnostic molecular marker for zebra mussels (Dreissena polymorpha) and
      potentially co-occurring bivalves: mitochondrial COI.
AB  - We report diagnostic differences in the nucleotide sequences of a 710-bp fragment
      of the mitochondrial cytochrome c oxidase subunit I gene (COI) from the zebra
      mussel (Dreissena polymorpha) and potentially co-occurring bivalves: the quagga
      mussel (Dreissena bugensis); the Asiatic clam (Corbicula fluminea), the dark
      false mussel (Mytilopsis leucophaeata), and the wedge clam (Rangia cuneata). The
      COI sequence of the deep-water "profunda" phenotype of the quagga mussel was
      nearly identical to that of shallow-water quagga mussels. Restriction fragment
      length polymorphisms (RFLPs) in this portion of COI produced species-specific
      differences in fragment numbers and sizes that could be used as diagnostic
      markers to distinguish the free-living larvae produced by these bivalves.

PMID- 8869515
TI  - DNA sequence variation of mitochondrial large-subunit rRNA provides support for a
      two-subclass organization of the Anthozoa (Cnidaria).
AB  - We have sequenced a portion of the mitochondrial 16S rRNA gene from 29 species of
      Anthozoa, representing six orders of the subclasses Ceriantipatharia,
      Hexacorallia, and Octocorallia, with the focus on deep-seamount corals (> 500-m
      depth). We have detected significant length variation in the gene, with
      homologous gene fragments ranging from 545 bp in a shallow-water scleractinian
      coral to 911 bp in a deep-sea antipatharian black coral. The aligned sequences
      were divided into five regions: three high-identity sequence blocks (HSBs) and
      two highly variable blocks of insertions/deletions (INDELs). Most of the length
      variation among species occurred as varying numbers of nucleotides in the two
      INDELs. Little or no intraspecific sequence variation was detected over spatial
      scales of up to approximately 150 km. Interspecific sequence variation was lowest
      among the octocorals and greatest among the ceriantipatharians. Our data indicate
      that the orders Ceriantharia and Antipatharia are highly divergent, and a
      phylogenetic reconstruction provides support for the two-subclass system of the
      class Anthozoa (Hexacorallia and Octocorallia).

PMID- 8869516
TI  - Nucleotide sequence of the promoter region of Sparus aurata insulin-like growth
      factor I gene and expression of IGF-I in eggs and embryos.
AB  - A genomic fragment of 3.1 kb, containing the promoter region of Sparus aurata
      insulin-like growth factor I (IGF-I) gene has been cloned and sequenced. This
      fragment contains exon 1 and exon 2 of Sparus aurata IGF-I gene. These two exons
      are identical in organization to the reported chum salmon IGF-I gene. Exon 1
      contains 5' untranslated region and part of the signal peptide. Exon 2 codes for
      part of the signal peptide and part of the B domain. Nested polymerase chain
      reaction (PCR) revealed that a fragment was amplified from liver RNA when a
      common primer in the translated region and a primer located between 375 and 395
      nucleotides upstream of the first methionine were used. No such amplification was
      obtained when the primer was located between 414 and 434 nucleotides upstream of
      the first methionine, suggesting that the first exon in Sparus IGF-I gene starts
      400-410 nucleotides upstream of the first methionine. Expression of IGF-I mRNA
      was studied in Sparus aurata using reverse transcription (RT)-PCR. An amplified
      fragment was found in unfertilized eggs and in embryos 4, 8, and 12 hours after
      fertilization, when oligonucleotides specific for Sparus aurata IGF-I cDNA were
      used. A similar fragment was found when adult liver or one-day larval RNA were
      used. This fragment hybridized in a Southern blot to salmon IGF-I cDNA. These
      results demonstrate that the structure of IGF-I gene has been conserved in
      teleosts and IGF-I transcripts are present in fish during embryogenesis, probably
      of maternal origin.

PMID- 8869517
TI  - Do dinoflagellates contain a Cdc2-like protein kinase?
AB  - A protein present in extracts of the dinoflagellate Gonyaulax that was capable of
      binding an antibody directed against the conserved Cdc2 kinase epitope
      EGVPSTAIREISLLKE was characterized by Western blot analysis and DNA sequencing
      and shown not to encode a Cdc2 kinase. The amount, size, and isoelectric point of
      the immunoreactive species were invariant over a 24-hour period (encompassing S
      and M phases), and the DNA sequence of a cDNA isolated by immunologic screening
      showed that no conserved kinase regions were present in the deduced amino acid
      sequence. A method based on polymerase chain reaction (PCR), using primers
      designed from conserved regions in the Cdc2 kinases, was also unsuccessful in
      isolating a cdc2 gene homologue, although other kinases were identified.

PMID- 8869518
TI  - Growth enhancement in transgenic tilapia by ectopic expression of tilapia growth
      hormone.
AB  - The generation of transgenic fish with the transfer of growth hormone (GH) genes
      has opened new possibilities for the manipulation of growth in economically
      important fish species. The tilapia growth hormone (tiGH) cDNA was linked to the
      human cytomegalovirus (CMV) enhancer-promoter and used to generate transgenic
      tilapia by microinjection into one-cell embryos. Five transgenic tilapia were
      obtained from 40 injected embryos. A transgenic animal containing one copy of the
      transgene per cell was selected to establish a transgenic line. The transgene was
      stably transmitted to F1 and F2 generations in a Mendelian fashion. Ectopic, low
      level expression of tiGH was detected in gonad and muscle cells of F1 transgenic
      tilapia by immunohystochemical analysis of tissue sections. Nine-month-old
      transgenic F1 progeny were 82% larger than nontransgenic fish at p = .001. These
      results showed that low-level ectopic expression of tiGH resulted in a growth
      acceleration in transgenic tilapia. Tilapia GH gene transfer is an alternative
      for growth acceleration in tilapia.

PMID- 8869519
TI  - Molecular analysis of a RAPD marker (B20) reveals two microsatellites and
      differential mRNA expression in Penaeus vannamei.
AB  - We previously reported a population-specific DNA fragment (B20) in Penaeus
      vannamei shrimp, fragment found using the randomly amplified polymorphic DNA
      (RAPD) procedure, that was present in Population 2 but not in Populations 1 and
      4. The specific objectives of this study were to clone and sequence this genetic
      marker, determine if all or part of this cloned sequence could be found in any of
      the other populations in which this marker could not be amplified, and examine if
      this marker represents a functional gene by examining the steady-state levels of
      mRNA expression using Northern blot hybridization. Sequence information of the
      1259-bp B20 clone revealed two microsatellites and two candidate open reading
      frames. Although the entire B20 sequence could only be amplified in Population 2
      (from Ecuador), Population 3 (a hybrid of Populations 1 and 2), and a few
      individuals from wild Ecuadorian shrimp samples, portions of the B20 DNA could be
      amplified in individuals from Populations 1, 2, 3, candidate Population 4, and
      wild Ecuadorian samples. These microsatellites vary in size between populations
      and families. Northern blot hybridization analysis using radiolabeled B20 probe
      detected two mRNA transcripts of approximately 1.5 and 2.0 kb. Expression data
      throughout development indicated that these transcripts were present at low
      levels in nauplii from two of the three crosses examined using broodstocks of
      Population 1. Higher levels were observed in postlarvae (PL) 6, PL8, and PL10 in
      one of the three crosses. Individuals from all crosses showed higher levels of
      expression in the juvenile tail muscle. The mRNA transcript levels were
      undetected in zoea 3, PL2, and PL4 stages of development and broodstock tail
      muscle. The levels of expression of B20 mRNA transcripts varied significantly
      between Populations 1, 2, 3, 4, and wild Ecuadorian individuals as well as
      between families and within individuals representative of seven families from
      Population 1. In summary, the B20 clone revealed the presence of two
      microsatellites that vary in size between populations. These microsatellites will
      be useful for estimating genetic diversity within and between populations,
      identifying family-specific markers, and mapping loci responsible for
      economically important traits in penaeid shrimp. The mRNA levels detected by the
      B20 clone showed differential expression during development, and the pattern of
      expression was influenced by the genetic background of the parental crosses used.

PMID- 8869520
TI  - Macrosocial transition and health hazards.

PMID- 8869521
TI  - Social gradient of CVD risk in Germany before/after unification.
AB  - A social gradient of cardiovascular risk has been found in several European
      countries, including the former East and West Germany. Have any changes have
      occurred in Germany, particularly in the east, since the wall came down? We
      analyzed the results of three compatible, population-based, interview-and
      examination health surveys that were performed in both parts of Germany between
      1984 and 1992. Total years of education was the social indicator.
      Systolic/diastolic blood pressure, body mass index, prevalence of hypertension,
      obesity, and cigarette smoking showed a social gradient in favor of higher social
      class groups; the social gradient for total cholesterol and hyper-cholesterolemia
      in men was less clear. Despite a much higher risk-factor profile in the east,
      neither a difference between the social gradients of the former East and West
      Germany nor a clear trend after the wall came down were found. In both areas, the
      social gradient clearly increased only for women smokers. Overall, we found very
      little evidence to support the idea that the ferocity of socioeconomic changes in
      the east had already led to a higher gradient of cardiovascular risk in 1991/1992
      relative to that in the western part of the German population.

PMID- 8869522
TI  - Life expectancy in Germany: possible reasons for the increasing gap between East
      and West Germany.
AB  - The current life expectancy of East and West Germans is different. After the late
      1980s, life expectancy at birth in both regions, which was comparable in the
      early 1950s, became almost three years lower in East Germany. Life-table
      calculations of German birth cohorts since 1900 revealed that a difference
      between the groups in cardiovascular disease prevalence was associated with the
      difference in life expectancy. Whereas migration, environmental pollution, and
      health-care differences accounted for only a small part of the gap, evidence
      emerged that lifestyle and social patterns may have caused the less favourable
      trend in cardiovascular disease. The life-expectancy curve has flattened in East
      Germany while continuously increasing in West Germany. During the 1960s and
      1970s, such opposite trends were due to steeply increasing blood-pressure and
      cholesterol levels in East Germany and more favourable social development in West
      Germany--a better average social class (higher educational levels and a lower
      proportion of working-class individuals), a higher gross national product, and a
      higher proportion of GNP spent on health. Both the cardiovascular-risk-factor
      trends and the social gradient have contributed to the gap between the
      populations of East and West Germany in life expectancy.

PMID- 8869523
TI  - Dietary habits in Eastern Germany: changes after reunification and their relation
      to CHD risk profiles (DRECAN).
AB  - As part of the DREsden CArdiovascular risk and Nutrition study, 2038
      participants, selected from a cohort of 3076 workers in the Dresden area,
      underwent a detailed nutritional analysis of the periods before and after German
      reunification. Although protein, fat, carbohydrate, and total calorie intake did
      not change in Dresden after reunification, polyunsaturated fat replaced 17% of
      the saturated fatty acids, dairy product intake tripled, and fruit intake
      increased by 70%. Relative to a reference PROCAM 'western' cohort, the 90th
      percentile of triglycerides was higher in middle-aged men, and the levels of
      total cholesterol and HDLC were higher in all males. Serum LDLC levels in males
      and females were similar. Serum lipid concentrations and the prevalence of
      hyperlipidemia were similar to those of the PROCAM cohort, but smoking was less
      common. In young males and females, body mass index was higher; hypertension was
      more frequent. We assume that the differences in nutrition and risk profile
      before reunification were less substantial than commonly believed.

PMID- 8869524
TI  - Nutritional behaviour differences in Germany.
AB  - East- and west-German health inequalities that emerged in the 1960s and 1970s
      centered not only on cardiovascular mortality but also on lifestyle-dependent
      risk factors, thus a question that should be addressed is whether different
      dietary behaviours existed in the two sections of Germany. To answer this
      question, we examined two random-sample population surveys--MONICA in the east
      and VERA in the west--that were carried out during the late 1980s. In the eastern
      section of Germany, the consumption of milk, vegetable oil and fat, fresh
      vegetables and tropical fruits was much lower than that in the west, whereas the
      intake of sausages and butter was much higher. Consequently, the calorie intake
      in the east was higher for fat and lower for carbohydrates before reunification.
      Changes in dietary habits were anticipated in East Germany after reunification
      because of important changes in the food supply. Analysis of an east-German
      dietary survey that was carried out after the wall came down revealed that the
      improved food supply to the east, with more choices for planning a healthy diet,
      led to a favourable development in both macro- and micro-nutrient intake, more
      carbohydrates, vitamins, calcium, and potassium were consumed.

PMID- 8869525
TI  - Environmental health in the health-care professions: biological, physical,
      psychic, and social health hazards.

PMID- 8869526
TI  - Psychophysiological and epidemiological investigations on the dentist.
AB  - This paper selectively shows the results of a psychophysiological study in
      general dental work. The change in heart rate was a very meaningful indicator.
      The average stress during dental work can be classified from light to moderately
      severe. The form of the course of the 0.10 Hz frequency band, diverted from the
      spectral analysis of heart periods, was successfully used in dental work. The
      self-assessment scale of Nitsch was used to describe the strain experience.
      Analysis of the results revealed that dental work involves high psychic stress.
      Epidemiological values of occupational diseases completed the objective
      assessment of strain effects and consequences. Representative conclusions include
      (a) inclusion of dentists in occupational care; (b) ergonomic design of working
      areas and their use; and (c) coordinated advanced training in the field of dental
      work design.

PMID- 8869527
TI  - Pleural mesothelioma and household asbestos exposure.
AB  - This article discusses the development of asbestos-induced malignant
      mesotheliomas after non-occupational environmental exposure to asbestos through
      contact with occupationally exposed household members. In our policlinic, we have
      seen six fatal pleural mesothelioma cases (five wives and one son of asbestos
      industry workers) with no history of occupational asbestos exposure. In five
      women, a causal relation was established between the fatal disease and inhalation
      of asbestos fibers while cleaning the contaminated work-clothes and shoes of
      their husbands at home. The son had also been exposed to asbestos throughout his
      childhood during daily visits with his father at the workplace.

PMID- 8869528
TI  - Are biological antagonists an alternative to synthetic fungicides for preventing
      postharvest diseases of fruits and vegetables?
AB  - In recent years, both the public and health authorities have become increasingly
      concerned about the presence of pesticides in our food supply and the
      environment. As a direct result of this mounting concern, research efforts for
      the development of alternative methods for the control of postharvest diseases of
      fruits and vegetables have been intensified. Considerable attention has been
      placed on assessing the potential of the use of biological antagonists as a
      viable alternative to the use of synthetic fungicides. Naturally occurring
      microbial antagonists have been shown to control several rot pathogens on diverse
      commodities. Such antagonists have various modes of action: antibiosis or
      competition for nutrients and space or both, induction of resistance in the host
      tissue, and direct interaction with the pathogen. The commercialization of
      certain antagonists to control postharvest decay of fruits and vegetables appears
      to be feasible and may present an alternative to synthetic pesticides.

PMID- 8869529
TI  - The reticular zone of the rat adrenal gland 60 days after exposure to a chemical
      fertilizer.
AB  - The author examined the adrenal glands of rats that were kept in a workshop of an
      NPK fertilizer factory for 30 days and then for 60 days in the laboratory.
      Histochemical examination of the reticular zone revealed an increase in neutral
      lipids and triglycerides and a decrease in phospholipids. The nucleic acid
      content, predominantly RNA, was enhanced. Although the acid phosphatase activity
      was slightly lowered, both succinate dehydrogenase and monoamine oxidase
      activities were increased. The results indicate that exposure of rats to NPK
      fertilizer had a stimulating effect on the reticular zone of their adrenal
      glands.

PMID- 8869530
TI  - Environmental-health aspects of pulse-modulated microwaves.
AB  - Our theoretical model describes the potential influence of irradiation with pulse
      modulated microwaves on the conformational oscillations of enzymes in living
      organisms. Certain values of pulse-repetition time, determined by the period of
      conformational oscillations of the corresponding type of enzyme, can produce the
      effect at extremely low power levels. Synchronized oscillations in identical
      enzyme molecules produce in turn large-scale oscillations within living cells.
      Thus, short periods of exposure to pulse-modulated microwaves could be beneficial
      to cellular function, whereas maintaining the amplitude of such oscillations at a
      maximum for long periods may have a stressful effect on biochemical processes.
      The model discloses the possible environmental-health risks of long-term exposure
      in ambient fields that are created by radar, navigation, and communication
      systems.

PMID- 8869531
TI  - Why should there be a National Perinatal Association?

PMID- 8869532
TI  - An effective model for reorganization of perinatal services in a metropolitan
      area: a descriptive analysis and historical perspective.
AB  - The expansion and development of regionalized perinatal care has faltered during
      the past 10 years as clinical and financial polarization created by institutional
      and individual competition has supplanted original ethical and altruistic
      precepts. An integrated practice model is described for the reorganization of
      perinatal services on the basis of findings from nine community hospitals with
      level II nurseries developed and administered by a private practice group of
      neonatologists functioning in coordination with established university level III
      facilities and staff. Nine hospitals (seven private and two affiliated with a
      health maintenance organization) were located in urban and suburban communities
      in two counties within a 725-square-mile area encompassing a greater metropolitan
      area. Guidelines were created to define the level of care provided at each
      hospital. All neonates, including infants who had intended delivery at estimated
      gestational ages > or = 32 weeks, were at least initially provided care at their
      community hospital. Neonates who required assisted ventilation, surgical
      intervention, evaluation for suspected cardiac disease, or selective diagnostic
      procedures were transferred to one of the tertiary facilities. Gestational age
      and birth weight specific categories for the 36,014 neonates delivered in 1988 to
      1989 at the community practice hospitals are delineated for need of transport
      from level II to level III unit, deaths, and percent survival. Retrospective
      comparison of the community hospitals before and after establishment of the
      practice demonstrated a significant decrease in infants transported to a higher
      level of care and increase in neonates returned from level III to II units.
      Associated with improved capability of these level II nurseries was a reduction
      in mortality of neonates with diagnoses consistent with potential viability.
      Strict adherence to practice guidelines for maternal transfer resulted in
      significant reductions in delivery of low birth weight and very low birth weight
      neonates at level II community practice hospitals. The safety, efficacy, and
      potential cost effectiveness of this community hospital practice is discussed as
      a viable alternative model to the current widespread competitive disorganization
      that now characterizes regionalization of most metropolitan perinatal services.

PMID- 8869533
TI  - Exosurf versus Survanta surfactant preparations: proportional-hazards regression
      analysis of time to successful extubation and discontinuation of oxygen therapy.
AB  - Time to successful extubation (VENT-DC) and time to discontinuation of oxygen
      therapy (OX-DC) for infants treated with Exosurf and Survanta surfactant
      preparations were compared in an observational study. Proportional-hazards (Cox)
      regression was used to adjust for confounding by differences in baseline risk
      factors between treatment groups. The Exosurf/Survanta hazard ratios,
      representing the relative instantaneous probabilities of the next event (VENT-DC
      or OX-DC) occurring in the Exosurf versus Survanta groups, were close to the null
      value of 1.0 and were not statistically significant. For VENT-DC the ratio was
      1.08 (95% confidence interval 0.73 to 1.61, p = 0.60); for OX-DC the ratio was
      0.87 (0.58 to 1.30, p = 0.83). By contrast, the hazard ratios for female versus
      male sex and black versus white race, presented as internal reference values,
      were further from the null value and were statistically significant. Survival
      curves showing the estimated proportion of patients in whom VENT-DC or OX-DC was
      achieved over time were generated from the proportional hazards models. Our
      findings suggest that any difference between Exosurf and Survanta surfactant for
      VENT-DC or OX-DC is likely considerably smaller than the differences associated
      with gender or race. The rationales for (1) using proportional-hazards regression
      when duration of therapy is an outcome of interest and (2) generating internal
      reference risk ratios when multivariate analysis is used are discussed in
      relation to future studies of hyaline membrane disease or other problems of
      prematurity.

PMID- 8869534
TI  - Computer versus lecture: strategies for teaching fetal monitoring.
AB  - The purpose of this study was to determine how well novice nurses learned basic
      fetal monitoring concepts from a computer-assisted instructional program and a
      scripted lecture with equivalent content. A pretest-posttest experimental design
      was conducted. Forty-eight junior baccalaureate nursing students beginning their
      first maternity rotation were recruited for the study from a southwestern
      university. Thirty-nine students provided complete data sets. None had prior
      experience or education in fetal monitoring. Two strategies were used to teach
      basic fetal monitoring concepts: a scripted lecture with black-and-white
      transparencies and an equivalent computer-assisted instructional program.
      Statistical significance was set at p = 0.05. There were no significant
      differences between the computer and lecture groups' learning on the basis of
      age, education, or vision. There was a positive, nonsignificant gain in mean
      scores from the pretest to the posttest for both groups. The greatest difference
      was in the program completion time with the computer-assisted instruction group
      completing the program 43.6% faster than the lecture group.

PMID- 8869535
TI  - A semipermeable skin dressing for extremely low birth weight infants.
AB  - Skin breakdown and high fluid requirements are common problems in extremely low
      birth weight infants that may be reduced by application of a semipermeable skin
      dressing (SPD). An SPD was applied to 39 study infants who weighed < 1000 gm
      (control subjects, n = 37) to determine whether it would protect the skin and
      decrease fluid requirements. Randomization occurred before 12 hours of life and
      SPD was applied to the chest, abdomen, and back. Sixty-one infants survived the
      first 14 days. Skin remained nonerythematous, intact, and undamaged under the
      dressing, whereas uncovered skin sustained significant breakdown in both groups.
      No significant differences were found in fluid or electrolyte status. Although
      the SPD did not affect fluid requirements, the significant improvement in skin
      integrity under the SPD may justify its use in premature infants with delicate
      skin.

PMID- 8869536
TI  - The CLIPED procedure: an attempt to improve perinatal outcome in hopeless
      situations.
AB  - The purpose of this study was to prevent delivery in women who at < 23 weeks'
      gestation were in premature labor with excessive cervical dilation and membranes
      prolapsed into the vagina. Six patients were seen at gestational ages of 17 to
      22.5 weeks in premature labor with cervical dilatation of 2 to 8 cm and membranes
      prolapsed into the vagina. There were three singleton pregnancies, two sets of
      twins, and one set of triplets. Cerclage placement was successful in five of six
      patients and one patient had ruptured membranes at operation. One fetus died the
      day after successful cerclage. The average prolongation of gestation was 33 days
      in the remaining four patients. It is our opinion that the poor prognosis of a
      patient at < 23 weeks' gestation in premature labor with excessive cervical
      dilatation and membranes prolapsed into the vagina may be altered with cerclage
      placement. We suggest that patients at > or = 21 weeks' gestation with prolapsed
      membranes whose contractions have been stopped be considered for cerclage late in
      pregnancy with excessive dilation (CLIPED procedure). The average amount of time
      a gestation is prolonged may preclude the procedure before 21 weeks.

PMID- 8869537
TI  - Pulse oximetry in newborn infants with birth weights of 620 to 4285 grams
      receiving dopamine and dobutamine.
AB  - The reliability of pulse oximetry in neonates receiving inotropic drugs because
      of hypotension and microcirculatory perfusion failure has not been well
      documented. Signal loss of the pulse oximeter in adult patients receiving
      dopamine infusions has been reported. To evaluate the relationship between pulse
      oximeter oxygen saturation (SaO2) and co-oximeter directly measured oxygen
      saturation, we studied 30 infants in the first 4 days of life (birth weight 620
      to 4285 gm, gestational age 26 to 43 weeks) receiving dopamine (30 patients) and
      dobutamine (10 infants). Infants had normal blood pressures at the time of the
      study. To minimize motion artifact a Nellcor N-200 (Nellcor Incorporated,
      Hayward, Calif.) oximeter with electrocardiographic synchronization was used. We
      compared pulse oximeter values with simultaneous arterial samples analyzed for
      oxygen saturation with an IL 282 co-oximeter (Instrumentation Laboratory, Inc.,
      Lexington, Mass.). The values were corrected for spuriously elevated
      carboxyhemoglobin levels and fetal hemoglobin level was quantitatively measured.
      The partial pressure of oxygen at 90% hemoglobin saturation for each patient was
      calculated. The dosage of dopamine ranged from 4 to 28 micrograms/kg per minute
      and the dosage of dobutamine varied from 4 to 24 micrograms/kg per minute. Over a
      wide range of values for mean blood pressure (23 to 66 mm Hg), partial pressure
      of oxygen at 90% hemoglobin saturation (43.1 to 70.2 mm Hg), and oxygen
      saturation (SaO2 80% to 100%), linear regression analysis revealed a close
      correlation between pulse oximeter SaO2 and co-oximeter SaO2 values (r = 0.83,
      standard error of the estimate 2.2%, p < 0.0001). Our findings indicate that
      pulse oximetry can be used reliably for continuous oxygen monitoring in
      normotensive neonates with an SaO2 of 80% to 100% who are receiving dopamine and
      dobutamine.

PMID- 8869538
TI  - Maternal varicella history as a predictor of varicella immune status.
AB  - We sought to determine the sensitivity of maternal history as a predictor of
      varicella immune status during pregnancy. A total of 514 women were prospectively
      questioned about history of varicella infection at the time of their first
      prenatal visit. Eighty-one patients who gave either negative or uncertain
      histories of prior infection had blood drawn and analyzed for presence of
      varicella antibodies. Women with negative histories had a significantly lower
      rate of serologic varicella immunity than women with uncertain histories (46.9%
      vs 93.8%, p < 0.001); these women were also significantly younger than those with
      either uncertain or positive histories. Patient payer status and number of
      children were also analyzed; neither was significantly associated with varicella
      seropositivity. The certainty of a pregnant woman's varicella infection history
      was the strongest single predictor of her actual immune status. These results
      should be helpful both for patient counseling and for possible development of
      prenatal varicella screening protocols.

PMID- 8869539
TI  - Effect of transfusion and phlebotomy on serum ferritin levels in low birth weight
      infants.
AB  - The objective of this study was to determine the degree to which the balance of
      red blood cells between transfusions and phlebotomies affects iron stores,
      represented by serum ferritin levels, in low birth weight infants. A
      retrospective review was made of transfusions, phlebotomies, and ferritin level
      before initiation of oral iron administration in 29 low birth weight infants with
      a mean birth weight of 1001 +/- 304 gm (+/- 1 SD) and gestational age of 27.0 +/-
      1.8 weeks. Correlation was determined between ferritin level and net balance of
      red blood cells, maturity, or age. Serum ferritin levels correlated with
      estimated net red blood cells gained or lost (r = 0.87, p < 0.0001, 95%
      confidence intervals 0.74 to 0.94). Serum ferritin level can be a useful guide to
      estimating iron stores in low birth weight infants who have undergone transfusion
      and phlebotomy. How serum ferritin level could be used to guide initiation of
      oral iron supplementation needs further study.

PMID- 8869540
TI  - Perinatal mortality: the role of hospital of birth.
AB  - OBJECTIVE: Patterns of perinatal mortality in a state with no organized system or
      guidelines for regionalized perinatal health care were examined. STUDY DESIGN:
      Vital statistics on live births, fetal deaths, and neonatal deaths in Arkansas
      for 1985 through 1989 were analyzed by birth hospital level of obstetric care,
      birth weight, and county of residence. Birth weight-specific fetal and neonatal
      mortality rates (NNMR) were compared by level of obstetric care at the birth
      facility; multivariate logistic regression models estimated the odds of NNMR by
      level of obstetric hospital, adjusted for other risk factors. RESULTS: Infants of
      < 2000 gm birth weight tend to have lower NNMR when born at level III hospitals
      than when born at level II facilities. The proportion of very low birth weight (<
      1500 gm) and moderately low birth weight (1500 to 2499 gm) infants delivered at
      level III hospitals in Arkansas is lower than that in other states with formal
      systems of perinatal regionalization. CONCLUSIONS: Although Arkansas's NNMR
      compares favorably with the national average, further reductions would be likely
      were a formal system of perinatal regionalization implemented in this state.

PMID- 8869541
TI  - Silicone-rubber catheter fracture and embolization in a very low birth weight
      infant.
AB  - A 28-week preterm infant had a percutaneous silicone-rubber central venous
      catheter placed for parenteral nutritional support. The catheter was later found
      to have fractured, and a 5.5 cm piece of catheter was lodged in the patient's
      right atrium. It was retrieved percutaneously by fluoroscopically guided cardiac
      catheterization without complications. Fracture and embolization of a catheter is
      a rare but serious complication of central venous catheters, and we report our
      experience as the only known case of a silicone-rubber catheter fracture and
      embolization in a premature infant, in which the catheter fragment was retrieved
      via a percutaneous endovascular approach.

PMID- 8869542
TI  - Conceptualization, measurement, and use of gestational age. I. Clinical and
      public health practice.
AB  - Despite its importance for both clinical and public health practice and the
      considerable effort spent during the past three decades to develop alternative
      estimation methods, the measurement of gestational age on both the individual and
      population level continues to be problematic. The availability of alternative
      approaches for the estimation of gestational age has to some extent obscured the
      basic differences in the conceptualization of these measures and influenced our
      current state of thinking about gestational age. As the evidence grows that these
      alternative gestational age estimation measures do not precisely correspond with
      one another, controversies have arisen regarding which method is most accurate.
      In the search for a single gestational age "gold standard," the potentially
      valuable information that these alternative measures may provide when used in
      combination should not be overlooked.

PMID- 8869544
TI  - Compassionate care and comfort guidelines.

PMID- 8869543
TI  - Manslaughter or a legitimate parental decision? The messenger case.

PMID- 8869545
TI  - Perinatal testicular torsion and the hard testicle.
AB  - Perinatal testicular torsion in the neonate is uncommon. However, early diagnosis
      is important to enable timely surgical exploration. The presence of a hard testis
      should raise the suspicion of perinatal torsion. The cases of two infants with
      this disease process are presented. The rationale for scrotal exploration is
      discussed.

PMID- 8869546
TI  - Predictors of depression symptoms in pregnant adolescents.
AB  - The purpose of this study involving a cross-cultural group of single, pregnant
      adolescents was to examine the association of depression with self-esteem, social
      support, discomforts of pregnancy, and selected sociodemographic variables. The
      sample comprised 62 pregnant adolescents recruited from a residential maternity
      home. Subjects ranged in age from 14 to 20 years (mean 16.67 years) and were
      predominantly Hispanic and black. All subjects completed the Center for
      Epidemiological Studies Depression Scale, Coopersmith's Self-Esteem Inventory, a
      physical discomfort checklist, and a sociodemographic questionnaire. A high level
      of depression symptoms was reported by the majority of participants. Nearly two
      thirds of the young women reported adequate levels of emotional support; however,
      the remaining subjects claimed inadequate levels. Results of the multiple
      regression analyses revealed that, of the predictor variables investigated, only
      the total self-esteem score was statistically significant (p = 0.0001) and
      explained 32.6% of the variance. In further statistical analysis a multifactor
      analysis of variance found social support to be a significant variable
      influencing depression. On the basis of these results, several recommendations
      for assessment and intervention with similar groups of pregnant adolescents are
      suggested, including screening for depression symptoms and development of
      treatment programs for affected youth.

PMID- 8869547
TI  - Perinatal pathology casebook.
AB  - Citrullinemia, a rare inborn error of metabolism, is characterized by a
      deficiency of argininosuccinic acid synthetase that results in large increases in
      plasma ammonia, citrulline, and glutamine, with normal acid-base balance. The
      neurologic symptoms vary from poor feeding, vomiting, and irritability to
      hypotonia, apnea, and death. The most common pathologic findings at autopsy are
      cerebral edema and focal neuronal necrosis. We describe a case of fulminant
      citrullinemia in an infant in whom the major pathologic findings included diffuse
      cerebral edema and a lack of overt metabolic derangement characteristic of
      neonates with a urea cycle defect. Our case differs from the classic presentation
      of citrullinemia in that subarachnoid hemorrhage was identified early in the
      clinical course. We report the first observation of subarachnoid hemorrhage in an
      infant with a urea cycle defect.

PMID- 8869548
TI  - Fulminant neonatal citrullinemia complicated by subarachnoid hemorrhage.

PMID- 8869549
TI  - Congenital adrenal hyperplasia.

PMID- 8869550
TI  - Analgesic effects of the neurosteroid 3 alpha-androstanediol.
AB  - The efficacy of 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Androstanediol;
      3 alpha-Diol) and 4-pregnen-3,20-dione (progesterone; P) in promoting analgesia
      was investigated. Ovariectomized rats received daily injections of 3 alpha-Diol
      (0.6, 3.0, 6.0 and 7.5 mg/kg) or vehicle and twice daily injections of estradiol
      17 beta (E2: 1 microgram) for 2 days. Progesterone (0.5, 1.0, 2.0 and 4.0 mg/kg)
      or its vehicle was given on the third day and nociceptive testing using the
      radiant heat tailflick method was carried out 4 h later. In Expt. 1, P and 3
      alpha-Diol both produced analgesia and had biphasic dose-response effects when
      administered singly. 3 alpha-Diol (3.0 mg/kg) elevated tailflick latencies in E2
      primed animals above those following vehicle, 6.0 or 7.5 mg/kg 3 alpha-Diol; 6.0
      and 7.5 mg/kg produced elevations that were greater than vehicle but less than
      3.0 mg/kg. Progesterone (0.5 and 1.0 mg/kg) also elevated tailflick latencies
      above vehicle controls, while 2.0 and 4.0 mg/kg produced intermediate effects. In
      Expt. 2, 3 alpha-Diol (3 alpha-Diol:BSA) and P (P:BSA) conjugated to bovine serum
      albumin (BSA) were applied to the medial basal hypothalamus (MBH) and preoptic
      area (POA) to ascertain whether the steroids' analgesic actions were mediated by
      membrane actions in these sites. Free P and P:BSA both increased tailflick
      latencies when applied to the MBH, while 3 alpha-Diol and 3 alpha-Diol:BSA
      elevated latencies when applied to the POA, suggesting the steroids' effects
      occur in part at the neuronal membrane. In Expt. 3, free P or P:BSA applied to
      the MBH did not increase tailflick latencies if systemic P was given
      concurrently. Similarly, free 3 alpha-Diol and 3 alpha-Diol:BSA implants into the
      POA failed to increase tailflick latencies if s.c. 3 alpha-Diol was co
      administered. These data indicate that P and 3 alpha-Diol at moderate doses have
      analgesic effects in part via membrane actions within the MBH and POA,
      respectively.

PMID- 8869552
TI  - Differential expression of neurofilament protein in the visual system of the
      vervet monkey.
AB  - It has been previously reported that the monoclonal antibody SMI-32 reveals a
      characteristic pattern of immunostaining which may be used to delineate various
      cortical modules in the monkey visual system. We wished to examine staining
      patterns with this antibody at both the lateral geniculate nucleus (LGN) and
      cortical levels with regard to magno- and parvocellular processing schemes in the
      vervet monkey. Using standard immunohistochemical procedures, we have found that
      the M-layers of the LGN were intensely stained in comparison to P-layers and that
      there were regional variations in staining within the visual cortex that
      reflected this input. The transition between areas V1 and V2 was especially
      prominent due to differences in the laminar staining profiles. Another striking
      result was found within the superior temporal sulcus where heavy SMI-32
      immunostaining confined to the floor of the sulcus coincided with a similar zone
      of intense myelin staining. We have also found a number of other areas within the
      intraparietal and lateral sulci that show foci of heavy SMI-32 staining. As with
      Cat-301 immunostaining, the regional variabilities that are observed with SMI-32
      in the visual cortex reflect molecular distinctions that may provide further
      criteria for functional segmentation.

PMID- 8869551
TI  - ARPP-21: murine gene structure and promoter identification of a neuronal
      phosphoprotein enriched in the limbic striatum.
AB  - ARPP-21 (cAMP-regulated phosphoprotein, Mr = 21,000 on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis) is a phosphoprotein highly enriched in
      concentration in the neurons of the limbic striatum. It is likely a third
      messenger in the intracellular cascade of events following neuronal stimulation
      by first-messenger activators of the adenylate cyclase system, including dopamine
      via the D1 receptor. ARPP-21 expression is restricted to telencephalic post
      mitotic, post-migrational neurons, and its precise pattern of temporal and
      spatial expression makes it an attractive candidate for the study of
      transcriptional regulation of neuronal maturation. To define genomic regions
      likely to contain functional promoter elements, we isolated the murine ARPP-21
      gene. Primer extension and T2 RNase protection analyses identified multiple
      transcription start sites, but 1.3 kb of 5'-flanking DNA revealed few consensus
      transcription factor binding sequences. A series of transient transfection assays
      in clonal cell lines which do not express ARPP-21 identified a basal promoter
      active in both neuronal and non-neuronal lines. Expression in all lines was
      decreased by the inclusion of regions further upstream, and extinguished by the
      inclusion of the first intron. Further analyses are likely to reveal cell
      specific regulatory sequences.

PMID- 8869553
TI  - SC1: a marker for astrocytes in the adult rodent brain is upregulated during
      reactive astrocytosis.
AB  - Astrocytes are the most abundant cell type in the mammalian central nervous
      system (CNS), and are involved in many processes critical for normal CNS
      maintenance and function. We have used double-label immunocytochemistry and in
      situ analysis to show that the SPARC (secreted protein acidic and rich in
      cysteine)-related protein SC1, co-localizes with the astrocyte marker glial
      fibrillary acidic protein (GFAP) in the adult rodent brain. Thus, SC1 is an
      astrocyte marker that may be used to investigate astrocyte heterogeneity and
      analyze glial cell lineages during neural development. Consistent with the
      presence of SC1 and GFAP in astrocytes, both proteins were markedly upregulated
      following reactive astrocytosis induced by focal mechanical trauma. Therefore,
      SC1 may play an important role in reactive astrocytosis subsequent to a wide
      variety of neural trauma, including neurodegenerative diseases and acute neural
      damage.

PMID- 8869554
TI  - Up-regulation of functional voltage-dependent sodium channels by cyclic AMP
      dependent protein kinase in adrenal medulla.
AB  - Treatment of cultured bovine adrenal chromaffin cells with dbcAMP increased
      [3H]STX binding with an EC50 of 126 microM and a half-effective time of 12 h;
      dbcAMP (1 mM x 18 h) raised the Bmax approximately 1.5-fold without altering the
      Kd value. Forskolin (0.1 mM) or IBMX (0.3 mM) also increased [3H]STX binding,
      while dbcGMP had no effect. Effects of dbcAMP and forskolin were abolished by H
      89, an inhibitor of cAMP-dependent protein kinase. Cycloheximide (10
      microgram/ml) and actinomycin D (10 microgram/ml), inhibitors of protein
      synthesis, nullified the stimulatory effect of dbcAMP, whereas tunicamycin, an
      inhibitor of protein glycosylation, had no effect. Treatment with dbcAMP
      augmented veratridine-induced 22Na influx, 45Ca influx via voltage-dependent Ca
      channels and catecholamine secretion, while the same treatment did not alter 45Ca
      influx and catecholamine secretion caused by high K (a direct activation of
      voltage-dependent Ca channels) [25]. Na influx via single Na channel calculated
      from 22Na influx and [3H]STX binding was quantitatively similar between non
      treated and dbcAMP-treated cells. Brevetoxin allosterically enhanced veratridine
      induced 22Na influx approximately 3-fold in dbcAMP-treated cells as in non
      treated cells. These results suggest that cAMP-dependent protein kinase is
      involved in the modulation of Na channel expression in adrenal medulla.

PMID- 8869555
TI  - Effect of galanin and enterostatin on sympathetic nerve activity to interscapular
      brown adipose tissue.
AB  - The effects of galanin and enterostatin on sympathetic activity have been
      examined in rats using electrophysiological techniques. Galanin, in doses of 25
      300 pmol, and enterostatin, in doses of 0.5-10 nmol, were injected into the third
      ventricle of anesthetized male Sprague-Dawley rats in 1-microliter volumes.
      Galanin produced a dose-dependent suppression (ranging between 20 and 80%) of
      sympathetic firing rate of nerves innervating interscapular brown adipose tissue.
      In rats fed a chow diet, injection of enterostatin produced only a transient 10%
      rise in firing rate which returned to baseline within 10-15 min. In contrast,
      animals fed a high-fat diet showed a dose-dependent increase in firing rate
      lasting for 60 min. The results of this experiment are consistent with the
      hypothesis that food intake and sympathetic nervous system activity have a
      reciprocal relationship. The implications of this relationship are discussed.

PMID- 8869556
TI  - Purification and characterization of human endopeptidase 3.4.24.16. Comparison
      with the porcine counterpart indicates a unique cleavage site on neurotensin.
AB  - We have purified and characterized human brain endopeptidase 3.4.24.16. The
      enzyme behaved as a 72 kDa protein and belonged to the metalloprotease family.
      Human endopeptidase 3.4.24.16 cleaved neurotensin at a unique site at the Pro10
      Tyr11 bond, leading to the formation of neurotensin(1-10) and neurotensin(11-13).
      The kinetic parameters displayed by human endopeptidase 3.4.24.16 towards a
      series of natural neuropeptides indicated that bradykinin was the most
      efficiently proteolysed. Angiotensin I, dynorphins 1-8 and 1-9 and substance P
      also behaved as good substrates while neuromedin N, angiotensin II, leucine and
      methionine enkephalin and neurokinin A resisted degradation by human
      endopeptidase 3.4.24.16. We have purified the porcine counterpart of
      endopeptidase 3.4.24.16 and compared its ability to cleave neurotensin with that
      of the enzyme from human origin. It appeared that, besides a major production of
      neurotensin(1-10), an additional formation of neurotensin(1-8) was observed with
      the pig enzyme, suggesting a cleavage of neurotensin not only at the Pro10-Tyr11
      bond but also at the Arg8-Arg9 peptidyl bond. The latter cleavage appeared
      reminiscent of endopeptidase 3.4.24.15 since this peptidase was reported to
      cleave neurotensin at the Arg8-Arg9 bond. Our study indicated that neurotensin(1
      10) formation by porcine endopeptidase 3.4.24.16 could be potently blocked with
      the selective endopeptidase 3.4.24.16 dipeptide inhibitor Pro-Ile without
      interfering with neurotensin(1-8) formation. By contrast, the formation of the
      latter product was highly potentiated by dithiothreitol and inhibited by the
      endopeptidase 3.4.24.15 inhibitor Cpp-Ala-Ala-Tyr-pAB, two effects that were not
      observed for neurotensin(1-10) production. Altogether, our results indicate that
      porcine endopeptidase 3.4.24.16 cleaves neurotensin at a unique site, leading to
      the formation of neurotensin(1-10) and that the production of neurotensin(1-8) is
      due to contaminating endopeptidase 3.4.24.15.

PMID- 8869557
TI  - Kinetic analysis of glutamate transport by the miniswine choroid plexus in vitro.
AB  - Transport of glutamic acid by the choroid plexus, the blood-cerebrospinal fluid
      (CSF) barrier, was investigated by using the isolated choroid plexi from the
      fourth (FVCP) and lateral ventricles (LVCP) of the young adult miniswine in
      vitro. Glutamic acid uptake was very pronounced, with concentrations 7-fold
      (LVCP) and 2.4-fold (FVCP) higher in tissue than in medium after only 5 min of
      incubation with 1 microM glutamic acid. Tissue/medium ratios reached steady state
      by 15 min at 30-fold (LVCP) and 11-fold (FVCP). Uptake was energy-dependent and
      inhibited by ouabain and hypothermia. L-Aspartic acid was shown to be inhibitory
      in a concentration-dependent manner, suggesting that it shares a common transport
      system, whereas neither octanoic acid nor okadaic acid (transported by a separate
      fatty acid system) inhibited glutamic acid transport. At the same temperature,
      the labeled metabolite of glutamate (glutamine) in the tissue was 64.7%, 73.2%,
      and 72.5% of total radioactivity at 5, 30, and 60 min, respectively. The
      estimated Km values for glutamate uptake by the choroid plexus are 264 microM
      (FVCP) and 196 microM (LVCP); Vmax values are 87 (FVCP) and 147 (LVCP)
      nmol/g/min, respectively. These results indicate that, in addition to the
      metabolism of glutamate to glutamine, an active uptake mechanism is present in
      the choroid plexus of miniswine which may serve to regulate glutamic acid
      concentration in the CSF.

PMID- 8869558
TI  - Autoradiographic localization of dihydrotestosterone and testosterone
      concentrating neurons in the brain of the oyster toadfish.
AB  - Vertebrate species with male mating calls or songs tend to have sexually
      dimorphic sonic neurons that concentrate gonadal steroids. The distribution of
      [3H]dihydrotestosterone- and testosterone-concentrating neurons was examined in
      oyster toadfish (Opsanus tau), males of which produce a courtship boatwhistle
      call. Labeled cells in the forebrain were found in the posterior nucleus of the
      dorsal telencephalon (Dp), a pallial structure, the supracommissural nucleus of
      the ventral telencephalon (Vs), nucleus propticus parvocellularis anterior (PPa)
      and other preoptic nuclei, the ventral, dorsal and caudal hypothalamus. Positive
      brainstem areas included the optic tectum, torus semicircularis, nucleus
      lateralis valvula, a periventricular nucleus of the rostral medulla and the
      inferior reticular formation. Compared to estrogen, androgens labeled fewer sites
      in the forebrain and more in the brainstem. Two of the positive sites, Vs and
      PPa, have been implicated in boatwhistle production. Many sites that connect to
      these areas in teleosts likewise concentrate steroids. Unlike the situation in
      frogs, birds, and one other teleost, the toadfish sonic motor nucleus did not
      concentrate androgens. Androgen labeling in the posterior nucleus of the dorsal
      telencephalon represents the first autoradiographic demonstration of steroid
      concentration in the pallium of a teleost forebrain.

PMID- 8869559
TI  - Galanin microinjected into the medial septum inhibits scopolamine-induced
      acetylcholine overflow in the rat ventral hippocampus.
AB  - Galanin-like immunoreactive terminals hyperinnervate the basal forebrain
      cholinergic neurons in Alzheimer's disease. To investigate the hypothesis that
      galanin acts directly on basal forebrain cell bodies, in vivo microdialysis
      studies were conducted in awake rats which analyzed the actions of galanin on
      acetylcholine release. Microinjection of galanin into the cholinergic cell body
      region of the medial septum-diagonal band (MS-DBB) inhibited acetylcholine
      release in the ventral hippocampus. These results are consistent with an
      interpretation that galanin terminals synapsing on cholinergic cell bodies of the
      basal forebrain may serve to inhibit the release of acetylcholine in the terminal
      fields of the cholinergic neurons.

PMID- 8869560
TI  - Serotonergic antagonists impair arousal-induced phase shifts of the circadian
      system of the syrian hamster.
AB  - Single episodes of arousal of Syrian hamsters 2 h before projected activity onset
      (i.e., CT 10) phase-advanced their free-running circadian rhythm of wheel
      running. Serial arousal once every 23 h or once every 23.5 h for 7 days caused
      large composite phase-advances to the wheel-running rhythm, the latter period
      being more effective in supporting an interval of stable entrainment. Pre
      treatment of hamsters at CT 6 with the serotonergic antagonist ritanserin (1-5
      mg/kg, which acts at both 5-HT2 and the putative 5-HT7 receptor, impaired the
      phase-advancing response to arousal at CT 10 but the drug was without effect on
      phase advances induced by exposure to light. Pre-treatment with a second
      serotonergic antagonist, ketanserin (1-5 mg/kg), which is without effect at 5-HT7
      but has high affinity for 5-HT2 receptors, was also effective in attenuating the
      phase advancing effect of arousal at CT 10. However, neither agent was able to
      achieve complete blockade of the phase advances. These results are discussed in
      relation to in vitro and in vivo studies in the rat which have identified a role
      for 5-HT7 receptors in serotonin-mediated circadian entrainment.

PMID- 8869561
TI  - Intracerebroventricular injection of choline increases plasma oxytocin levels in
      conscious rats.
AB  - In the present study, we examined the effect of intracerebroventricularly
      (i.c.v.) injected choline on both basal and stimulated oxytocin release in
      conscious rats. I.c.v. injection of choline (50-150 micrograms) caused time- and
      dose-dependent increases in plasma oxytocin levels under normal conditions. The
      increase in plasma oxytocin levels in response to i.c.v. choline (150 micrograms)
      was greatly attenuated by the pretreatment of rats with atropine (10 micrograms;
      i.c.v.), muscarinic receptor antagonist. Mecamylamine (50 micrograms; i.c.v.), a
      nicotinic receptor antagonist, failed to suppress the effect of 150 micrograms
      choline on oxytocin levels. Pretreatment of rats with 20 micrograms of
      hemicholinium-3 (HC-3), a specific inhibitor of choline uptake into nerve
      terminals, greatly attenuated the increase in plasma oxytocin levels in response
      to i.c.v. choline injection. Osmotic stimuli induced by either oral
      administration of 1 ml hypertonic saline (3 M) following 24-h dehydration of rats
      (type 1) or an i.c.v. injection of hypertonic saline (1 M) (type 2) increased
      plasma oxytocin levels significantly, but hemorrhage did not alter basal oxytocin
      concentrations. The i.c.v. injection of choline (50, 150 micrograms) under these
      conditions caused an additional and significant increase in plasma oxytocin
      concentrations beyond that produced by choline in normal conditions. These data
      show that choline can increase plasma oxytocin concentrations through the
      stimulation of central cholinergic muscarinic receptors by presynaptic mechanisms
      and enhance the stimulated oxytocin release.

PMID- 8869562
TI  - Ca2+/calmodulin-dependent protein kinase II in postsynaptic densities after
      reversible cerebral ischemia in rats.
AB  - Compartmentalization of protein kinases and association of the enzyme with
      strategic cellular substrates may be important for regulating signal transduction
      in neurons. Cerebral ischemia produced by transient 20 min occlusion of common
      carotid and vertebral arteries in rats caused a dramatic (3-fold) increase in
      Ca2+/Calmodulin-dependent protein kinase II (CaM-KII) in the fraction enriched in
      postsynaptic density (PSDf), the compartment of the neuron that is involved in
      signal transduction. This change in compartmentalization was not reversible for
      up to 24 h after termination of the occlusion and was followed by reduction of
      CaM-KII to 50% of control content one week after the insult. The observed changes
      in CaM-KII content did not represent general protein redistribution in PSDf after
      ischemia since there were no parallel changes in PSDf actin concentration. The
      redistribution of CaM-KII coincided with gradual (up to 80%) reduction of its
      activity in PSDf as tested using specific peptide substrate and endogenous CaM
      KII substrates. This work provides evidence that ischemia disturbs CaM-KII
      distribution and activity in PSDf and this may lead to long lasting disruption of
      signal transduction at the synaptic level.

PMID- 8869563
TI  - Time-dependent fusimotor effects on the discharge of cat primary muscle spindle
      afferents induced by a long-lasting succinylcholine infusion.
AB  - The responses of 46 Ia afferents from the tibial anterior muscle of the cat to
      repetitive ramp-and-hold stretches were investigated under a succinylcholine
      (SCh) infusion of 120 micrograms.kg-1.min-1 lasting 15 to 25 min. It was possible
      to distinguish four consecutive phases of the effect of the SCh on the
      responsiveness of the Ia afferents. The first three of these four phases have
      already been described. We analysed in more detail the changes from Phase III to
      the end of Phase IV. Static fusimotor effects were dominant in the discharge
      patterns obtained during Phase III; dynamic fusimotor effects prevail at the end
      of Phase IV. Our observations were quantified by comparing the mean values of
      initial activity, final static value, dynamic response and slow receptor
      adaptation read from the discharge patterns obtained during Phase III with the
      mean values of the same parameters obtained from discharge patterns from the end
      of Phase IV: the two mean values were significantly different for each of the
      four measurements. This change from Phase III to the end of Phase IV is highly
      specific for each spindle. To demonstrate this spindle specificity, discharge
      patterns were selected from among those produced by each Ia afferent in Phase III
      and at the end of Phase IV. Each of these discharge patterns was assigned to one
      of six categories. Category I displays purely dynamic fusimotor effects and
      Category VI purely static fusimotor effects. Categories II, IV and V display
      combinations of static and dynamic fusimotor effects with an increasing admixture
      of static fusimotor effects. The spindle-specific change from Phase III to the
      end of Phase IV is defined in terms of the specific degree of change from a
      higher-number to a lower-number category in the case of each of the 46 Ia
      afferents. In the discussion a combination of activity by the two nuclear bag
      fibres of a spindle is deduced from the specific discharge pattern of each
      category. The conclusion from these considerations is that results obtained from
      the administration of SCh have to be interpreted with great caution in making any
      statement about the existence of a dynamic bag1 fibre in a spindle.

PMID- 8869564
TI  - Presence of brain-derived neurotrophic factor in brain and human and rat but not
      mouse serum detected by a sensitive and specific immunoassay.
AB  - Brain-derived neurotrophic factor (BDNF) is one of several endogenous proteins
      that play key roles in neuronal development and homeostasis. We describe here the
      characterization and use of a sensitive and specific enzyme-linked immunoassay
      (EIA) for BDNF protein. Recombinant BDNF was detected at concentrations as low as
      10 pg/ml, whereas the EIA did not detect NT-3, NT-4/5, or NGF at concentrations
      as high as 100 ng/ml. Because BDNF protein sequences are identical among humans,
      mice, and rats, we utilized the BDNF EIA to detect BDNF in the circulation or
      brain regions of these species. High concentrations of BDNF were detected in
      human and rat serum, and up to 50-fold lower BDNF levels were present in citrated
      human or rat plasma. The BDNF signal (66-141 pg/ml) in 20% human plasma was
      completely blocked by pre-exposure of plasma to a monoclonal antibody (Mab)
      specific for BDNF but not by exposure to 5-fold greater concentrations of an
      irrelevant Mab of the same isotype (IgG1). There was a significant and positive
      correlation (r = +0.86) between plasma levels of BDNF and serotonin, an
      indoleamine that is specifically released from activated platelets. These results
      are consistent with the view that the BDNF detected in human and rat plasma is
      derived from platelet degranulation, and that circulating levels of BDNF are
      negligible. In contrast to human or rat serum, mouse serum contained no
      detectable BDNF. However, BDNF protein was readily detectable at 108-256 ng/g of
      tissue in hippocampus, frontal cortex, and neostriatum of mice and rats. Thus,
      the failure to detect BDNF in murine serum was not due to an assay defect but
      highlights a significant species difference in the tissue-specific expression of
      BDNF that may be of biological importance. The presence of BDNF protein in blood
      and brain regions at quantities which greatly exceed those described for NGF
      confirm the abundant distribution of this broadly-acting neurotrophic factor.

PMID- 8869565
TI  - Effects of reversible inactivations of the medial septal area on reference and
      working memory versions of the Morris water maze.
AB  - Involvement of the medial septal area (MSA) in reference memory and working
      memory versions of the Morris water maze (MWM) task was investigated in rats with
      reversible inactivation of this area by drugs injected through a single cannula
      aimed at the MSA. In Experiment 1, rats were trained in a reference memory
      version of the MWM with two blocks of four trials per day for 3 consecutive days.
      Acquisition was impaired by pretrial MSA injection of 10 ng tetrodotoxin (TTX) in
      1 microliter saline but not of saline alone into MSA. In Experiment 2,
      intraseptal injection of TTX (10 ng, 1 microliter) immediately after two blocks
      of four trials had no effect on the consolidation of spatial reference memory. In
      Experiment 3, intraseptal injection of TTX (10 ng, 1 microliter) impaired
      retrieval of well established spatial reference memory in rats which had received
      8 trials per day for 3 consecutive days. In Experiments 4 and 5, rats were
      trained in a working memory version of MWM task to find a new target position in
      trial 1 and retrieval of this information was tested 75 min later in trial 2.
      Intraseptal injection of lidocaine (4%, 1 microliter) prior to training impaired
      working memory performance while immediately posttraining injection of lidocaine
      had no effect. It is concluded that normal activity of the MSA is necessary for
      the memory formation at the time of training but its involvement in posttraining
      consolidation is unlikely. The MSA function is required for retrieval of well
      established spatial reference memory.

PMID- 8869566
TI  - Thapsigargin enhances carotid body chemosensory discharge in response to hypoxia
      in zero [Ca2+]e: evidence for intracellular Ca2+ release.
AB  - To test the hypothesis that Ca2+ is released from intracellular store in the
      carotid body glomus cells during hypoxia, we stimultaneously measured
      chemosensory discharge and tissue PO2 of perfused-superfused cat carotid body
      before and during flow interruption in the presence and absence of extracellular
      [Ca2+] with and without thapsigargin (1-10 microM). Ca(2+)-free solution
      increased the latency of sensory response, and decreased the rate of rise and
      peak activity but thapsigargin significantly influenced these responses, without
      affecting oxygen consumption. Since thapsigargin depletes the intracellular Ca2+
      store, and since Ca2+ is needed for the sensory discharge, these results suggest
      that intracellular release and influx of Ca2+ occur during hypoxia.

PMID- 8869567
TI  - Calretinin is largely localized to a unique population of striatal interneurons
      in rats.
AB  - Previous studies have reported the presence of the calcium binding protein
      calretinin in neurons in the striatal part of the basal ganglia in rats and
      primates. In the present study, immunofluorescence double-labeling techniques and
      immunofluorescence combined with retrograde labeling were used in rats to
      determine whether calretinin is found in any of the known types of striatal
      neurons. The results showed that a small fraction of the calretinin-containing
      neurons (< 10%) contain parvalbumin, but none of the calretinin-containing
      striatal neurons contained markers for the other two major types of striatal
      interneurons (i.e., choline acetyltransferase-containing cholinergic neurons and
      somatostatin-containing neurons). Additionally, calretinin was not found in
      projection neurons, using either calbindin or DARPP32 as immunofluorescent
      markers of striatal projections neurons in general, or using retrograde labeling
      to specifically identify either striatonigral or striatopallidal neurons. Thus,
      calretinin appears to be largely found in a unique population of striatal
      interneurons in rats. This population appears to be about one third the abundance
      of any of the previously identified populations of striatal interneurons.

PMID- 8869568
TI  - Patterns of growth inhibitory factor (GIF) and glial fibrillary acidic protein
      relative level changes differ following left middle cerebral artery occlusion in
      rats.
AB  - Growth inhibitory factor (GIF) has been identified as a new metallothionein-like
      protein, the level of which is decreased in the Alzheimer's disease brain. GIF
      and glial fibrillary acidic protein (GFAP) have been reported to be expressed in
      reactive astrocytes in the rat brain following stab wounds. Moreover, strong
      expression of GIF mRNA in reactive astrocytes after ventricular injection of
      kainic acid has been demonstrated. To clarify the biological functions of GIF and
      GFAP in repair of the CNS, we examined changes in their relative levels to sham
      control using a Western blotting technique in the rat left hemisphere following
      occlusion of the left middle cerebral artery, for 28 days after surgery. The GIF
      relative level declined to 56% of the sham-operated control value on day 7.
      Thereafter the GIF relative level increased and returned to the normal relative
      level by days 21-28. The GFAP relative level increased from day 3 and reached a
      maximum of 120% of the sham-operated control value on days 14-21. While GIF and
      GFAP were both detected in reactive astrocytes, an increase in the GFAP relative
      level occurred prior to an increase in GIF relative level following the ischemia.
      The patterns of changes in relative expression levels of GIF and GFAP were quite
      similar to those in our previous studies on effects of cerebral stab wounds in
      rats, although the changes were more rapid in the previous studies. GIF and GFAP
      appear to play different roles in the repair of the CNS. The present results also
      indicated that GIF could play an important role in CNS repair after cerebral
      ischemia and provide new insights into the mechanism of gliosis investigated
      mainly from the viewpoint of GFAP.

PMID- 8869569
TI  - Seamlessness in personality and its derangements.
AB  - A significant but often overlooked aspect of the circumplex structure of the
      domain of interpersonal functioning is its systematically continuous ordering of
      the quality of the behavioral variations addressed. It is a domain, in other
      words, explicitly lacking in categorical boundaries wherein a given behavior can
      be sharply discriminated from others proximal to it within a shared circumplex
      space; any identified border is at best a "fuzzy" one characterized by blending
      and interpenetration. It is argued that this observation has extended
      generalizability in respect to the organization of personality, rendering moot
      and suspect taxonomic systems that postulate categorical entities. The Diagnostic
      and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric
      Association, 1994) used in the "diagnosis" of purported derangements of
      personality is one such system, one that would therefore be expected to yield
      certain predictable anomalies. These problems are illustrated with reference to
      the widespread occurrence of artifactual "comorbidities" among psychiatric
      diagnoses.

PMID- 8869570
TI  - A clinician-friendly version of the interpersonal circumplex: structural analysis
      of social behavior (SASB).
AB  - Like the original Interpersonal Circumplex (IPC), the Structural Analysis of
      Social Behavior (SASB) model was developed in the clinic. Different from and more
      complicated than the IPC, the SASB model nonetheless is parsimonious. It is
      consistent with Leary's (1957) original goal of bringing objectivity and clarity
      to the diagnostic process while acknowledging the complexity and variety of human
      nature. SASB applications extend from diagnosis into the domains of etiology and
      treatment. Specific advantages that accrue from the SASB model's more complex
      structure and assessment techniques include the ability to: (a) define both
      hostile and friendly differentiation, (b) specifically link social learning
      experiences with self-concept, (c) define several predictive principles on an a
      priori basis and confirm them in a variety of data sets, (d) assess personality
      at all 5 of Leary's levels, (e) define normality and pathology in qualitative
      rather than quantitative terms, (f) compare and contrast self-ratings with
      observer ratings using the same metric, (g) generate reasonable parallel models
      for affect and cognitive style that can help account for "comorbidity" between
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American
      Psychiatric Association, 1994) Axes I and II, (h) make contributions to
      understanding personality as a hypothetical construct (i.e., to make testable
      predictions about etiology and specific treatment interventions), (i) dissect
      complex communications into their underlying components, and (j) accurately
      characterize a given relationship through a relatively brief sample of behavior.

PMID- 8869571
TI  - From communications to interpersonal theory: a personal odyssey.
AB  - This contribution to the special issue reviews my theoretical and research
      journey into contemporary interpersonal theory and research. A seminal period
      involved conceptualization of a "communications" approach to psychotherapy and
      culminated in development of the Impact Message Inventory (IMI). Generation of
      the IMI necessitated immersion within the interpersonal circumplex measurement
      tradition and resulted in an "interpersonal communication" theory, combining
      concepts from both traditions, which appeared initially in the Handbook of
      Interpersonal Psychotherapy (Anchin & Kiesler, 1982). Subsequent research has
      concentrated on circumplex refinement of both the IMI and a second inventory, the
      Check List of Interpersonal Transactions, which was derived directly from the
      Interpersonal Circle. A continuing theme is the notion that precise and
      replicable tests of contemporary interpersonal theory, especially of
      interpersonal complementarity, require circle inventories that possess ideal
      psychometric and circumplex properties.

PMID- 8869572
TI  - The study of interpersonal problems: a Leary legacy.
AB  - The Inventory of Interpersonal Problems (IIP) is an instrument based on Leary's
      original theory that has been used to identify dysfunctional patterns in a
      person's interpersonal interactions. Interpersonal problems can be organized in 2
      dimensions, and the 2-dimensional space can be divided into 8 equal sectors
      (octants). Subscales of the IIP describe problems in each of these octants. The
      instrument has been used to identify interpersonal problems that are discussed
      most often in a brief dynamic psychotherapy and problems that are treated most
      easily. The results show that problems in the "exploitable" octant improve most
      frequently, whereas problems in the "dominating," "vindictive," and "cold"
      octants do not improve as readily. We have also examined people's attachment
      styles in adulthood (following a model proposed by Bowlby) and found that
      different attachment styles correspond to different types of interpersonal
      problems.

PMID- 8869573
TI  - Standardizing procedures for calculating rorschach interrater reliability:
      conceptual and empirical foundations.
AB  - Although the Rorschach test has demonstrated significant refinements in
      reliability, validity, and statistical power as a result of the procedural
      standardization and scoring innovations introduced by Exner's Comprehensive
      System, the issue of Rorschach interrater reliability remains unexplored. This
      article examines the psychometric foundations of Rorschach interrater reliability
      and applies notions from applied behavioral analysis to the treatment of
      Rorschach data. We empirically compare 3 methods of quantifying interrater
      agreement, their accuracy in estimating interrater agreement, and efficiency in
      reducing error in Rorschach research. Results indicate that the magnitude of
      differences between methods of quantifying interrater agreement and the
      associated reductions of error are significant. We propose a standard method for
      quantifying interrater agreement in Rorschach research.

PMID- 8869574
TI  - Using diagnostic efficiency statistics to evaluate the concurrent validity of the
      perceptual aberration scale.
AB  - We evaluated the diagnostic efficiency of the 35-item Perceptual Aberration Scale
      (PAS; Chapman, Chapman, & Raulin, 1978) in selecting schizotypal college students
      using the presence of a Minnesota Multiphasic Personality Inventory (MMPI;
      Hathaway & McKinley, 1940) code type associated with the schizophrenia spectrum
      as indicative of schizotypal status. The PAS was able to reliably rule out the
      presence of schizotypy among women and men producing very low (< or = 3) PAS
      scores. Among women, only extremely high PAS (> or = 28) reliably predicted
      schizotypal MMPI status. Among men, however, no PAS cutting score was reliably
      associated with the presence of a schizophrenia-related MMPI code type,
      suggesting that the PAS should not be used to define schizotypy among male
      college students. The PAS cutoff values that maximized accurate identification of
      women with schizotypal features and identification of women and men without
      schizotypal features are considerably more conservative than those that have been
      traditionally used in research using the PAS as a screening device. The data
      presented here suggest that using traditional PAS cutoffs (scores > or = 2 SD
      above the mean and < or = .5 SD below the mean) may result in unacceptably high
      diagnostic error.

PMID- 8869575
TI  - Projection on projective techniques = pathology: the problem that is not being
      addressed.
AB  - A replication of the "levels effect" and reported correlation of "projection" and
      "pathology" was undertaken using a selected set of Thematic Apperception Test
      (Murray, 1943) cards varied for ambiguity and scored for pathology and
      projection. The levels effect was not found for pathology in either a normal or
      psychiatric group, but was found for projection in the normal group. The
      correlation between projection and pathology was again clearly confirmed. It was
      concluded that failure to take into consideration the stimulus properties of the
      cards and the context in which the test was administered may lead to false
      attribution of pathology to normal test-takers.

PMID- 8869576
TI  - Teaching the Rorschach and learning psychodiagnostic testing: a commentary on
      Hilsenroth and Handler (1995).
AB  - A recent report by Hilsenroth and Handler (1995) surveyed graduate students'
      impressions of their predoctoral-level training on the Rorschach method. My
      commentary underscores two central points from their article: (a) the problem of
      program specialization in a crowded curriculum, and (b) students' indication of a
      need for more secure grounding in personality theory and clinical diagnosis. The
      focus of these remarks concerns current trends in clinical psychology education,
      their implications for training in psychological assessment, establishing a
      reasonable upper limit of solid competence for achieving a journeyman level of
      ability, and some considerations about a suitable role for continuing education
      workshops. A sharp distinction between filing in gaps in knowledge and
      compensating for fundamental deficiencies is emphasized in this context.

PMID- 8869577
TI  - Use of the MMPI-2 in the outpatient assessment of women with Anorexia Nervosa or
      Bulimia Nervosa.
AB  - Past research has shown that women with eating disorders commonly display
      clinical elevations on several scales of the Minnesota Multiphasic Personality
      Inventory (MMPI; Hathaway & McKinley, 1983), so the MMPI may be useful for the
      differentiation of women with Anorexia Nervosa from those with Bulimia Nervosa.
      In the study presented here, 116 women diagnosed with either Bulimia Nervosa or
      Anorexia Nervosa completed the Minnesota Multiphasic Personality Inventory-2
      (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Multivariate analyses
      failed to reveal any differences among the diagnostic subtypes. Consideration of
      profile code types was suggestive of possible group differences that mirror those
      discussed in previous literature on the personality features of women with eating
      disorders. Results are discussed with regard to past research and the clinical
      utility of the MMPI in the outpatient assessment of women with Anorexia Nervosa
      or Bulimia Nervosa.

PMID- 8869578
TI  - Construction of a personal development competitive attitude scale.
AB  - Theory development and research in the area of psychologically healthy
      competition has been impeded by the lack of a psychometrically sound instrument.
      Four studies were conducted as part of a research program designed to remedy this
      deficiency by constructing an individual difference measure of general personal
      development competitive attitude with satisfactory psychometric properties. In
      Studies 1 and 2, a 15-item scale was derived primarily through item-total
      correlational analysis; it demonstrated satisfactory internal and test-retest
      reliabilities. Studies 3 and 4 were concerned with establishing the construct
      validity of the scale. Both Studies 3 and 4 showed the scale's discriminant
      validity through its lack of association with hypercompetitiveness. In addition,
      its construct validity was seen in its negative association with neurosis and its
      positive links with personal and social self-esteem and optimal psychological
      health. Also, as expected, personal development competitiveness was positively
      correlated with needs for affiliation, whereas hypercompetitiveness was unrelated
      to affiliation needs. Although hypercompetitive individuals were more aggressive,
      dominant, and exhibitionistic, this was not the case for personal development
      competitors.

PMID- 8869579
TI  - Interpersonal Hostility Assessment Technique: description and validation against
      the criterion of coronary artery disease.
AB  - High levels of hostility are associated with adverse health outcomes. The
      Interpersonal Hostility Assessment Technique (IHAT; Barefoot, 1992) measures
      hostility from verbal behavior during a standardized interview. Four types of
      behaviors are scored as hostility: evading the question, irritation, and indirect
      and direct challenges to the interviewer. The sum of the frequencies of these
      acts is a Hostile Behavior Index (HBI), which is divided into two components:
      verbal, scored with speech content in mind, and paraverbal, based on vocal
      stylistics. This study examined characteristics of IHAT assessments in 129 male
      coronary patients. Satisfactory interrater reliabilities were obtained. The HBI
      correlated highly (.58) with coronary artery disease severity after controlling
      for traditional risk factors. This relation was not affected by question topic or
      by differential weighting of the four hostile behaviors. Both HBI components were
      significantly correlated with disease. Results are discussed in terms of their
      implications for hostility assessment.

PMID- 8869580
TI  - Test-taker and close-other selection of personality inventory feedback.
AB  - Results from previous studies suggest that normal persons self-enhance both when
      rating their own personality traits, and when evaluating personality inventory
      feedback. In this study, 64 male and female undergraduates attempted to
      distinguish their own California Psychological Inventory (Gough, 1975) profiles
      from those of two other individuals. Sixty-four close friends and relatives
      ("close others") of test-takers also attempted to identify test-taker profiles.
      It was found that a significant proportion of test-takers, and a near-significant
      proportion of close others, made accurate selections, Z = 3.76, p < .001 and Z =
      1.90, p = .06, respectively. It was also found that close others who selected
      incorrectly were significantly likely to flatter the test-taker by choosing the
      most favorable profile of the three, Z = 1.97, p < .05, whereas test-takers who
      selected incorrectly did not show a significant tendency to choose the most
      favorable profile.

PMID- 8869581
TI  - The Splitting Index: construction of a scale measuring the defense mechanism of
      splitting.
AB  - The Splitting Index (SI), a self-report scale based on the writings of Kernberg
      (e.g., 1976) on self and object representations and the defense mechanism of
      splitting, was constructed. After development over the course of 6 pilot studies,
      the SI was validated through 2 further studies. Factor analyses revealed a 24
      item scale with three 8-item subscales, measuring the splitting of self, family,
      and others' images. The SI and its subscales were demonstrated to be internally
      consistent and stable over a 4-week period. Convergent validity was supported by
      significant correlations with measures of borderline and narcissistic personality
      disorders, self-image stability, self-esteem, depression, and negative
      affectivity. Discriminant validity was demonstrated by near-zero correlations
      with two measures of cognitive complexity. Contrary to predictions, the SI was
      significantly correlated with the Dogmatism Scale (Rokeach, 1960), a third
      measure of cognitive complexity. Research and clinical applications of the SI are
      discussed.

PMID- 8869582
TI  - MCMI-III diagnostic validity: bad test or bad validity study.
AB  - Operating characteristics describe the validity of tests that attempt to
      dichotomously predict a diagnosis. These statistics are not fully published in
      the Millon Clinical Multiaxial Inventory-III Manual (MCMI-III manual; Millon,
      1994). When calculated from available statistics, the positive predictive powers
      of the MCMI-III scales are poor both in absolute terms and relative to the MCMI
      II (Millon, 1987). There were a number of problems, however, with the initial
      MCMI-III validity study both inherently and in execution. Although it is doubtful
      that the MCMI-III is weaker than the MCMI-II, a new validity study is needed.

PMID- 8869583
TI  - Effects of long-term food reduction on the hypothalamus-pituitary-thyroid axis in
      male and female rats.
AB  - The reduced thyroid activity during short-term starvation is associated with a
      lowered hypothalamic synthesis and secretion of TRH. However, little is known
      about the cause of the reduced thyroid function during prolonged malnutrition. We
      have therefore studied the effects of food reduction to one-third of normal
      (FR33) on the hypothalamus-pituitary-thyroid axis of male and female Wistar rats.
      After 3 weeks body weights of FR33 rats were almost 50% lower than those of
      controls. In both sexes, FR33 caused marked increases in serum corticosterone,
      and decreases in serum TSH, thyroxine (T4), free T4, tri-iodothyronine (T3) and
      free T3. While the free T3 fraction (FFT3) in serum decreased, the free T4
      fraction (FFT4) tended to increase. Electrophoretic analysis indicated that
      decreased FFT3 was correlated with an increased thyroxine-binding globulin, while
      the increase in FFT4 seemed due to a decreased thyroxine-binding prealbumin
      binding capacity. Total RNA and proTRH mRNA in the hypothalamus were not affected
      by FR33. Median eminence and posterior pituitary TRH content tended to increase
      in FR33 rats, suggesting that hypothalamic TRH release is reduced in FR33 rats.
      Anterior pituitary TSH content was decreased by FR33 in both sexes, but pituitary
      TSH beta mRNA and TRH receptor status were not affected except for increased
      pituitary TSH beta mRNA in female FR33 rats. Although FR33 had no effect on
      pituitary weight, pituitary RNA and membrane protein content in FR33 rats were 50
      70% lower than values in controls. In conclusion, prolonged food reduction
      suppresses the pituitary-thyroid axis in rats. In contrast to short-term food
      deprivation, the mechanism whereby serum TSH is suppressed does not appear to
      involve decreases in proTRH gene expression, but may include effects on pituitary
      mRNA translation. Our results further support the hypothesis that TSH release may
      be lowered by increased corticosterone secretion, although the mechanism of this
      effect may differ between acute starvation and prolonged food reduction.

PMID- 8869584
TI  - Fasting alters somatostatin binding to liver membranes of rainbow trout
      (Oncorhynchus mykiss).
AB  - Somatostatins are a diverse family of peptides that influence various aspects of
      animal growth, development, and metabolism. Recent work in our laboratory has
      shown that somatostatins stimulate hepatic lipolysis in rainbow trout. In this
      study we characterized somatostatin-binding sites in trout hepatic membrane
      preparations. We also examined changes in binding characteristics brought about
      by food deprivation. Binding of [Tyr11]-somatostatin-14 (SS-14) was saturable,
      reversible, and time- and temperature-dependent. Under optimal conditions,
      [Tyr11]-SS-14 specific binding averaged 5.7 +/- 0.3%. While SS-14 and SS-28 (an N
      terminally extended form of SS-14 and derived from the same gene as SS-14)
      displaced [Tyr11]-SS-14 specific binding (ED50 values of approximately 50 nM and
      100 nM respectively), salmon SS-25 (containing [Tyr7,Gly10]-SS-14 at its C
      terminus and presumably derived from a gene different from that giving rise to SS
      14/SS-28), except at pharmacological concentrations, did not. Significant
      specific binding was also detected in brain, esophagus, stomach, upper and lower
      intestine, pancreas, and adipose tissue. Scatchard analysis suggested the
      existence of two classes of hepatic somatostatin-binding sites: a high-affinity
      site with a Kd of 23 nM and Bmax of 1.4 pmol/mg protein and a low-affinity site
      with a Kd of 379 nM and Bmax of 4.9 pmol/mg protein. Fasting resulted in reduced
      growth and elevated plasma levels of SS-14 compared with fed animals. SS-14
      binding capacity of the high-affinity class in liver membranes isolated from
      fasted fish increased by 120% over that from fed counterparts. No difference in
      Kd for the high-affinity binding class or in either Kd or Bmax of the low
      affinity class was noted between fasted and fed animals. These data support the
      role of the liver as a target of somatostatin and suggest that fasting enhances
      hepatic sensitivity to SS-14 binding.

PMID- 8869585
TI  - Dopaminergic regulation of pituitary function in the late-gestation fetal sheep.
AB  - Development of the fetal ovine pituitary is essential for normal maturation and
      initiation of the parturition process, as well as for orchestrating endocrine
      responses to stress in utero. Increases in the biosynthesis of ACTH and prolactin
      (PRL) occur in the late-gestation fetal sheep pituitary. In the anterior lobe
      (AL) of the pituitary, pro-opiomelanocortin (POMC) biosynthesis and processing
      are primarily regulated by corticotrophin-releasing hormone and vasopressin.
      However, POMC in the intermediate lobe (IL) and PRL in the AL are known to be
      primarily regulated by dopamine, via the D2 receptor, in adult sheep. Because of
      the importance of ACTH and PRL during gestation we have investigated a potential
      role of dopamine in the control of both IL melanotrophs and AL lactotrophs and
      corticotrophs, in late gestation. Catheters were implanted into a maternal
      femoral artery and vein, fetal carotid artery and jugular vein as well as into
      the amniotic cavity. At day 130 of gestation, fetuses were infused intravenously
      with either the specific D2 receptor agonist bromocriptine (n = 5) or vehicle (n
      = 5), for 5 days. Blood samples were taken throughout the experiment and
      pituitaries were removed at the end of the treatment period. Bromocriptine caused
      a significant decrease (> 50%) in POMC mRNA levels in the IL. In contrast,
      bromocriptine had no significant effect on POMC mRNA levels or distribution in
      the AL. Fetal arterial ACTH and cortisol concentrations were unaffected by the
      bromocriptine infusion, compared with vehicle-infused controls. There was a
      dramatic decrease (> 80%) in plasma PRL concentrations, compared with the control
      fetuses. However, PRL mRNA levels in the AL were not significantly affected by
      bromocriptine. In conclusion, we have found that bromocriptine inhibits aspects
      of both melanotroph and lactotroph function in late-gestation fetal sheep. The
      data indicate that the fetal pituitary possesses functional D2 receptors in late
      gestation.

PMID- 8869586
TI  - Dihydropyridine-sensitive and -insensitive voltage-operated calcium channels
      participate in the control of glucose-induced insulin release from human
      pancreatic beta cells.
AB  - Calcium ion entry through voltage-operated calcium channels is a crucial step in
      the coupling of beta cell depolarization with insulin secretion. Various calcium
      channel subtypes have been shown to be coexpressed in single neurons and
      endocrine cells. Using the patch-clamp technique, we investigated the biophysical
      and pharmacological properties of calcium channels in freshly dispersed human
      pancreatic beta cells. Both low and high voltage activated currents were
      expressed, the two current types being easily distinguishable on the basis of
      biophysical criteria. The high voltage activated currents were not homogeneous:
      one component was affected by the dihydropyridine antagonist nitrendipine and the
      agonist Bay-K-8644; the other was insensitive to both dihydropyridines and omega
      conotoxin GVIA. In line with this pharmacology, nitrendipine reduced and Bay-K
      8644 increased glucose-induced insulin secretion from perifused human islets,
      whereas omega-conotoxin GVIA had no effect. However, about 20% of the glucose
      induced insulin release was found to be resistant to high nitrendipine
      concentrations. These data show that human pancreatic beta cells express
      heterogeneous voltage-operated calcium channels, only one of which is
      dihydropyridine-sensitive (L type). The L type channels are clearly involved in
      the control of insulin secretion, but our data suggest that dihydropyridine- and
      omega-conotoxin GVIA-insensitive channels may also play a role in the stimulus
      secretion coupling of human beta cells.

PMID- 8869587
TI  - Role of phosphoprotein phosphatases in the corpus luteum: I identification and
      characterisation of serine/threonine phosphoprotein phosphatases in isolated rat
      luteal cells.
AB  - Although the role of protein kinases and phosphorylation in steroidogenesis has
      received much attention, very little is known about the activities of
      phosphoprotein phosphatases (PP) and dephosphorylation in steroidogenic tissues.
      The aims of the present study were therefore to identify which of those
      serine/threonine PPs more commonly involved in intracellular signalling are
      expressed in rat luteal cells; to quantify, in vitro, the effects of inhibitors
      on PP activity extracted from purified rat luteal cells; and to measure the
      effects of PP inhibitors on the phosphorylation of endogenous luteal cell
      proteins. Polyclonal antibodies raised against the catalytic subunits of PP types
      1 and 2A, and a monoclonal antibody raised against the Ca(2+)-binding subunit of
      PP2B, were used to identify immunoreactive proteins that migrated on SDS-PAGE
      with approximate molecular masses of 37, 34 and 16 kDa, corresponding well with
      the reported molecular mass of PP1, PP2A and PP2B respectively. Five selective
      inhibitors of PP1/PP2A: okadaic acid, calyculin A, cantharidin, tautomycin and
      microcystin-RR, each caused a dose-dependent decrease in the activity of PPs in
      luteal cell homogenates, and also enhanced 32P incorporation into numerous luteal
      cell proteins; most notably, proteins with approximate molecular masses of 20 and
      22 kDa. The results of this study suggest that PPs may play an important role in
      the regulation of rat luteal cell functions.

PMID- 8869588
TI  - Role of phosphoprotein phosphatases in the corpus luteum: II control of
      progesterone secretion by isolated rat luteal cells.
AB  - The key role of protein kinases and protein phosphorylation in the regulation of
      luteal steroidogenesis is well documented. However the role of phosphoprotein
      phosphatases (PP) and dephosphorylation in the regulation of luteal cell
      progesterone secretion is as yet unknown. We have recently demonstrated the
      presence and activity of PP1 and PP2A in rat luteal cells and the present study
      was undertaken to determine the consequences of inhibiting PP activity in terms
      of progesterone secretion. Three structurally dissimilar inhibitors of PP1/2A,
      okadaic acid, calyculin A and cantharidin each caused a dose-dependent inhibition
      of LH-induced progesterone secretion without affecting cyclic AMP accumulation.
      The less potent derivative of okadaic acid, norokadaone, had no effect on either
      parameter, suggesting that the inhibitory actions on progesterone secretion are
      due to their specific actions on PP activity and that this inhibition occurs
      principally at a locus which is distal to the generation of cyclic AMP. In
      contrast to the inhibitory effects of PP1/2A inhibitors on progesterone
      biosynthesis, a PP2B inhibitor, cypermethrin, had no effect on LH-stimulated
      steroidogenesis. The three PP1/2A inhibitors also caused a concentration
      dependent inhibition of dibutyryl cyclic AMP-stimulated progesterone secretion.
      However, none of the inhibitors affected 22R-hydroxycholesterol-supported
      steroidogenesis, clearly demonstrating that the inhibitors did not interfere with
      the activity of steroidogenic enzymes. These results suggest that cycles of
      phosphorylation/dephosphorylation of specific proteins are required for the
      sustained production of progesterone. Whilst the precise location and function of
      putative PP substrates is uncertain, the present results indicate that they are
      involved in regulating the availability of free cholesterol to steroidogenic
      enzymes within mitochondria.

PMID- 8869589
TI  - Regulation of insulin-like growth factor-binding protein-4 protease activity by
      estrogen and parathyroid hormone in SaOS-2 cells: implications for the
      pathogenesis of postmenopausal osteoporosis.
AB  - The cellular mechanisms involved in the accelerated bone loss occurring in
      association with estrogen deprivation as seen following the menopause are not
      fully understood. Insulin-like growth factor-I (IGF-I) is the local regulator of
      osteoblasts and one of its binding proteins, insulin-like growth factor-binding
      protein-4 (IGFBP-4), binds to IGF-I and suppresses biological activity. Previous
      studies have shown that the binding activity of IGFBP-4 in the conditioned medium
      of parathyroid hormone (PTH)-treated SaOS-2 osteoblastic-like cells is enhanced
      twofold and that this PTH-enhanced IGFBP-4 binding activity is abolished by 17
      beta-estradiol. Levels of IGFBP-4 in the conditioned medium have been reported to
      be regulated not only at the level of production but also at the level of
      degradation which is catalyzed by a protease that specifically cleaves IGFBP-4.
      We have, therefore, studied the effects of 17 beta-estradiol and PTH on IGFBP-4
      protease activity using SaOS-2 cells. SaOS-2 cells produce a protease that
      specifically cleaves IGFBP-4 into two fragments of approximately 18 and 14
      kilodaltons. IGFBP-4 protease activity in the conditioned medium from PTH-treated
      cells was suppressed, while this PTH-induced suppression of protease activity was
      reversed by the addition of 17 beta-estradiol to the cultures. IGFBP-4
      proteolytic activity was stimulated by IGF-I or IGF-II added exogenously and was
      inhibited by EDTA or protease inhibitors. IGFBP-4 proteolyzed in the conditioned
      medium from cells treated with PTH and 17 beta-estradiol was less effective at
      inhibiting IGF-I-stimulated [3H]thymidine incorporation into DNA compared with
      that proteolyzed in the conditioned medium from PTH-treated cells. The simplest
      explanation is that 17 beta-estradiol suppressed the inhibitory effect of PTH on
      osteoblastic activity by inhibiting the PTH-induced suppression of IGFBP-4
      protease activity.

PMID- 8869590
TI  - A model of intrauterine growth retardation caused by chronic maternal
      undernutrition in the rat: effects on the somatotrophic axis and postnatal
      growth.
AB  - While it is well established that severe maternal undernutrition during pregnancy
      causes intrauterine growth retardation (IUGR), there has been relatively little
      study of the endocrine consequences and postnatal development of growth-retarded
      offspring. We have developed a model in the rat of IUGR by nutritional
      restriction of the mother throughout gestation and have examined the effects of
      fetal growth retardation on the endocrine and metabolic status during the
      perinatal period. Timed matings were performed in Wistar rats and dams were
      randomly assigned to one of two dietary treatment groups. Food was available ad
      libitum throughout pregnancy to a control group (at libitum group) and a
      restricted group was fed 30% of the ad libitum intake (restricted fed group).
      After birth, food was available ad libitum in both groups and litter size was
      adjusted to eight pups per litter. Dams lost a significant amount of body weight
      throughout gestation due to undernutrition but were able to catch up to the ad
      libitum group by day 10 postnatally. Litter size was not affected by maternal
      undernutrition. Maternal plasma IGF-I levels were significantly reduced in the
      restricted fed group throughout gestation (P < 0.001) but were not different
      postnatally. Maternal plasma IGF-binding proteins (IGFBPs)-1, -2 and -3 were
      significantly (P < 0.05) increased in the restricted fed dams. The mean body
      weights of fetuses in late gestation from the restricted fed dams were
      significantly lower (P < 0.001) in comparison with fetuses from control dams.
      Placental weights were also significantly (P < 0.01) reduced in the restricted
      fed compared with control dams. Body weights were significantly lower in the
      offspring of restricted fed dams than control dams from birth (P < 0.01) until 90
      days of age (P < 0.05). Nose-rump length was reduced in the fetuses of the
      restricted fed group at day 22 of gestation (P < 0.001) until weaning (P < 0.05).
      Plasma IGF-I levels were significantly reduced in the pups of restricted fed dams
      from day 22 of gestation (P < 0.01) until postnatal day 9 (P < 0.05) but were not
      significantly different at the later time-points. Plasma insulin levels were
      significantly reduced in the pups of restricted fed dams at birth (P < 0.05) but
      not at later time-points. Plasma IGFBP-1 and -2 levels were significantly
      increased in the offspring from restricted fed dams at day 22 of gestation, at
      birth and at day 9 postnatally (P < 0.05). 125I-Bovine GH specific binding to
      liver membranes was significantly lower (P < 0.05) in offspring from restricted
      fed dams at 21 days of age but not at 90 days of age. These data demonstrate that
      nutritional deprivation in the pregnant rat leads to IUGR and postnatal growth
      failure and to changes in allometric growth patterns and endocrine parameters of
      the somatotrophic axis postnatally.

PMID- 8869591
TI  - Attenuation of human chorionic gonadotropin release by nitric oxide in
      choriocarcinoma cell lines.
AB  - Nitric oxide (NO) is involved in the regulation of endocrine functions, but only
      a few studies have been reported about its role in placental hormone secretion.
      We investigated whether NO has any function in the release of human chorionic
      gonadotropin (hCG) in two different choriocarcinoma cell lines, JEG-3 and BeWo.
      First, nitric oxide synthase (NOS) was characterized in the choriocarcinoma
      cells. NOS activity was localized mainly in the particulate fraction and depended
      on calcium/calmodulin. Activity was inhibited by the presence of the L-arginine
      analog, NG-monomethyl-L-arginine (L-NMMA; 1 x 10(-4) M). Western blot analysis
      showed that the choriocarcinoma cells contained an endothelial isoform of NOS.
      The NO donor, sodium nitroprusside (SNP; 1 x 10(-5) and 1 x 10(-4) M),
      significantly inhibited hCG secretion in both choriocarcinoma cell lines. The
      suppression of hCG release by SNP (1 x 10(-5) M) was blocked by the addition of
      an NO scavenger, hemoglobin (1 x 10(-6) M). L-Arginine (1 x 10(-2) M), a NOS
      substrate, inhibited basal hCG secretion in JEG-3 cells. Incubation of the cells
      with L-NMMA (1 x 10(-4) and 1 x 10(-3) M) significantly increased hCG release.
      Exposure of both cell lines to increasing concentrations of a cyclic GMP analog
      (8-bromo-cyclic GMP; 1 x 10(-4) to 1 x 10(-2) M) caused a dose-dependent
      inhibition of hCG release. Cyclic GMP accumulation in response to SNP (1 x 10(-4)
      M), however, was not detected in either JEG-3 or BeWo cells. These data
      demonstrated that the endothelial isoform of NOS and a functional L-arginine-NO
      pathway are present in the choriocarcinoma cell lines. In addition, these
      findings support the hypothesis that NO produced in these cell lines is involved
      in the regulation of hCG secretion. We assume that although cyclic GMP is likely
      to play a role as a second messenger, a cyclic GMP-independent pathway cannot be
      excluded as a possible physiological mechanism in the attenuation of hCG release
      by NO.

PMID- 8869592
TI  - Long-term normalization of GLUT-4 protein content in skeletal muscle of diabetic
      rats following islet transplantation.
AB  - Skeletal muscle GLUT-4 content is decreased in streptozotocin (STZ)-diabetic
      rats. This decrease is associated with impairment in glucose transport across the
      plasma membrane. In this study we investigated whether islet transplantation
      might normalize GLUT-4 content. Transplantation of syngeneic islets restored long
      term near-normoglycemia in STZ-diabetic Lewis rats. Transplanted rats, followed
      up to 6 months, maintained slightly but significantly higher fasting and fed
      glucose levels when compared with age-matched normal controls. Although fasting
      insulin levels of transplanted rats were significantly higher than those of
      controls, insulin levels did not increase significantly with feeding. Plasma
      glucose levels following an oral glucose load (2 g/kg) were only slightly higher
      than in normal controls 2 months after transplantation, whereas after 6 months
      more severe glucose intolerance was detected. Transplanted rats completely lost
      the first-phase insulin release in response to i.v. glucose although they showed
      an increased second phase and preserved response to arginine. Six months after
      transplantation, endocrine beta cell mass of the grafts was similar to
      pretransplantation values. GLUT-4 protein content in skeletal muscle homogenates
      was reduced in untreated diabetic animals whereas it was completely restored by
      islet transplantation. In conclusion, achievement of long-term nearnormoglycemia
      after islet transplantation was associated with complete normalization of
      skeletal muscle GLUT-4 content in the diabetic animals, even in the presence of
      abnormal glucose tolerance and an altered pattern of insulin secretion.

PMID- 8869593
TI  - Pituitary and ovarian expression of the endogenous follicle-stimulating hormone
      (FSH) subunit genes and an FSH beta-subunit promoter-driven herpes simplex virus
      thymidine kinase gene in transgenic mice; specific partial ablation of FSH
      producing cells by antiherpes treatment.
AB  - The ovarian expression of the endogenous follicle-stimulating hormone beta
      subunit (FSH beta) and common alpha-subunit (C alpha) genes, and a herpes simplex
      virus thymidine kinase (tk) transgene, driven by a 2.3 kb bovine FSH beta
      promoter, was studied in normal and transgenic (tg) mice, tk functions not only
      as a neutral reporter that enables the study of the promoter function but also as
      an exogenously inducible toxigene. Reverse transcription-PCR followed by Southern
      blot hybridization with a nested probe was used to show the expression of the
      gene at the mRNA level. Common alpha-subunit mRNA was detected in the pituitary
      gland and ovaries of normal adult mice. We have previously detected endogenous
      FSH beta and tg tk mRNAs in the mouse pituitary, testis and ovary. In this study,
      the cellular localization of the corresponding proteins was visualized by
      immunocytochemistry. In normal mouse ovaries a positive reaction with FSH beta
      and C alpha antisera was seen in some of the corpora lutea and most prominently
      in the interstitial cells. A positive reaction with the tk antiserum was seen in
      the same cell types of tg mouse ovaries, but not in those of non-tg mice. Cell
      ablation-inducing treatment (gancyclovir, 20 mg/kg per day, for 14 days) of tg
      female mice reduced pituitary FSH concentrations by 52% (P < 0.05) but did not
      affect pituitary LH or plasma gonadotropins compared with non-tg females treated
      in the same way. A longer period of cell ablation induction (acyclovir 400 mg/kg
      per day, for 21 days) reduced not only pituitary but also plasma FSH
      concentrations (55 and 57% respectively; P < 0.05) without affecting LH. This
      treatment also reduced ovarian weight by 38% (P < 0.01). In conclusion, our
      results show first that the endogenous FSH beta and C alpha proteins are produced
      in the mouse ovary. Hence, endogenously synthesized FSH or its subunits may have
      a role in the paracrine regulation of ovarian function. Secondly, the FSH beta
      promoter directs the expression of tg tk in the pituitary gonadotrope cells, as
      shown by specific but partial ablation of FSH-producing cells after induction by
      gancyclovir and acyclovir. In the ovary, tk protein was localized to the same
      compartments as the endogenous gonadotropin subunit proteins. This further
      confirms our finding of ovarian expression of the FSH subunit genes.

PMID- 8869594
TI  - Stimulation of creatine kinase specific activity in human osteoblast and
      endometrial cells by estrogens and anti-estrogens and its modulation by
      calciotropic hormones.
AB  - We have previously demonstrated sex-specific stimulation of creatine kinase
      specific activity (CK) in bone cells both in vivo and in vitro, in primary
      culture cells derived from rat and human bone and in established human bone
      derived cell lines. We found that the female-derived cell line, SaOS-2, responded
      to 17 beta-estradiol (E2) by increased CK specific activity. The effects of E2 on
      the CK activity in SaOS-2 cells was inhibited by 100-fold excess of 4
      hydroxytamoxifen (Tam) as well as by the other antiestrogen, ICI 164,384. Tam by
      itself had some stimulatory effect whereas ICI 164,384 showed no estrogenic
      activity. We also demonstrated the estrogenic-like effect of another anti
      estrogen, raloxifene (Ral), which is agonist only in the SaOS-2 osteoblast-like
      cells but not in the human endometrial, Ishikawa cell line. Ishikawa cells
      respond to E2 and to Tam by increased CK activity. In both osteoblasts and
      endometrial cell lines, Ral and Tam were inhibitory in the presence of E2. The
      effects of E2 on SaOS-2 cells are at least partially mediated by the estrogen
      receptor (ER) at the level of transcription as demonstrated by transient
      transfection experiments using the human creatine kinase promoter chloramphenicol
      acetyltransferase in these cells. Pretreatment of SaOS-2 with calcitropic
      hormones, either 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) or human parathyroid
      hormone (1-34) (hPTH(1-34)) increased the stimulation of CK by E2 by 40-60%
      relative to E2 alone and significantly increased the sensitivity of the cells to
      E2 by lowering the effective hormonal dose needed for stimulation of CK by E2 by
      100-fold. This stimulatory effect of pretreatment of the cells with 1,25(OH)2D3
      was due to a 2.5-fold increase in the level of ER expression as measured directly
      by enzyme immunoassay in the SaOS-2/1 subline. The increase in the responsiveness
      to E2 by hPTH(1-34) was not due to an increase in ER level in the cells. We can
      conclude that in cell cultures as in vivo, Ral shows different effects depending
      on the cell type, namely estrogenic-like activity in skeletal cells but not in
      uterine cells. We can also conclude that as with rat-derived cells, in bone cells
      derived from human bone 1,25(OH)2D3 increased the sensitivity to E2 due to an
      increase in the number of ER in the cells, whereas PTH(1-34) augmented the
      response to E2 without increasing ER, by another, as yet unknown, mechanism.
      These studies suggest that the treatment of pathological bone disorders may be
      improved by combined hormone therapy.

PMID- 8869595
TI  - Mediation of the hormone- and serum-dependent regulation of thyroglobulin gene
      expression by thyroid-transcription factors in rat thyroid FRTL-5 cells.
AB  - The molecular mechanism for hormone- and serum-dependent regulation of
      thyroglobulin (TG) gene expression was studied. A construct of rat TG promoter (
      178 to -3) linked to a luciferase gene was transfected into TSH-, insulin- and
      serum-deprived FRTL-5 cells. Addition of TSH, insulin or serum augmented the
      luciferase activity. The endogenous TG mRNA level was also increased, indicating
      that the promoter used confers responsiveness of TG gene to these additives. The
      possible involvement of thyroid-transcription factors, TTF-1, TTF-2 and Pax-8, in
      the induction of TG gene transcription was studied using an electrophoretic
      mobility shift assay. Since the protein/DNA ratio in FRTL-5 cell extracts was
      significantly increased by these additives, binding activities of these factors
      per unit of DNA were examined. It was demonstrated that TSH, insulin or serum
      increased not only TTF-2 binding activity but also the binding activities of TTF
      1 and Pax-8. However, the magnitude of the increase in TTF-1 and Pax-8 mRNA
      levels per unit of DNA was less than that of the binding activity. Taken
      together, our results suggest that TSH, insulin and serum increase the binding
      activities of TTF-1 and Pax-8 to the TG promoter presumably through the
      posttranslational modification of the factors, thereby enhancing TG gene
      transcription.

PMID- 8869596
TI  - A type I collagen substrate increases PTH/PTHrP receptor mRNA expression and
      suppresses PTHrP mRNA expression in UMR106-06 osteoblast-like cells.
AB  - We have previously shown that the response of osteoblasts to parathyroid hormone
      (PTH) can be influenced at the receptor level by growth on the physiological
      substrate, type I collagen, or by treatment with retinoic acid. We have also
      shown differential expression of genes when cells of the osteoblast lineage are
      grown on type I collagen. The aim of this study was therefore to examine the
      effect of retinoic acid and growth on type I collagen on PTH/PTH-related protein
      (PTHrP) receptor mRNA expression in the osteosarcoma osteoblast-like cell line
      UMR 106-06. PTH/PTHrP receptor mRNA levels, as assessed by Northern blot, of
      cells grown on collagen were increased up to 2-fold compared with cells on
      plastic and in a concentration-dependent manner with respect to collagen. An
      increase was seen as early as 6 h and was maintained over a 24 h period. This was
      not due to increased mRNA stability. Retinoic acid decreased the level of
      receptor mRNA on both plastic and collagen at each time but did not alter mRNA
      stability. For all treatments PTH/PTHrP receptor mRNA abundance, relative to
      glyceraldehyde-3-phosphate dehydrogenase, increased steadily over 24 h after
      subculture of cells. In contrast, PTHrP mRNA levels were reduced in cells on
      collagen, compared with plastic. PTH-stimulated cAMP levels of cells grown on
      collagen were increased compared with plastic at 24 h, but not earlier.
      Consistent with the mRNA data, retinoic acid decreased the amplitude of cAMP
      responses in cells on plastic and collagen. There was no evidence for changes in
      adenylate cyclase per se, since forskolin-induced cAMP levels did not change with
      either treatment. This study shows that known modulators of osteoblast maturation
      also affect signal transduction in these cells by regulating gene expression of
      the PTH/PTHrP receptor as well as the PTHrP ligand.

PMID- 8869597
TI  - Thyroid hormone induces the synthesis of a putative protein in the rat granulosa
      cell which stimulates progesterone release.
AB  - 125I-3,5,3'-tri-iodothyronine (T3) binds specifically to a pure nuclear
      preparation from rat granulosa cells. A Scatchard analysis of T3 binding showed a
      Kd of 0.65 x 10(-9) mol/l and a Bmax of 1.57 pmol/mg DNA. The biological
      relevance of T3 binding to granulosa cells was evaluated by adding T3 (20
      ng/incubation) to granulosa cells (1 x 10(6) cells/incubation) which greatly
      stimulated progesterone release. T3-stimulated progesterone release was
      significantly inhibited by actinomycin-D (P < 0.01) and cycloheximide (P < 0.01).
      T3 caused about a twofold increase in granulosa cell protein synthesis as
      compared with the control which was inhibited by actinomycin-D and cycloheximide.
      The addition of T3 to granulosa cell incubations also resulted in a more than 2.5
      fold increase in mRNA. The results indicated that T3 stimulation of progesterone
      release is mediated via T3-induced protein(s) or TIP. TIP was located in the
      soluble supernatant fraction (100,000 g supernatant; 100 k sup) from T3-incubated
      cells but could not be detected in the 100 k sup from the control cells or LH
      incubated cells. TIP was purified based on its biological activity, i.e. its
      addition to granulosa cell incubations stimulated progesterone release into the
      medium. The 100 k sup from T3-incubated granulosa cells was subjected to Sephadex
      G-75 gel filtration, FPLC Mono Q and FPLC Superose 6 chromatography which
      resulted a 273-fold purification over the starting material and a clearly
      homogeneous protein was obtained. SDS-PAGE of purified TIP showed it to be a 53
      kDa monomer protein. Experiments conducted with radiolabelled TIP suggested
      internalization of TIP into the granulosa cell. The results therefore showed that
      T3 induces the synthesis of mRNA and proteins in rat granulosa cells and that one
      of the proteins is TIP which, in turn, stimulates progesterone release from the
      cell, suggesting thereby that this putative protein is a novel mediator of T3
      function in the granulosa cell.

PMID- 8869599
TI  - Evolution of growth hormone neurosecretory disturbance after cranial irradiation
      for childhood brain tumours: a prospective study.
AB  - To determine the aetiopathology of post-irradiation growth hormone (GH)
      deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH
      concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in
      35 prepubertal children, aged 1.5-11.8 years, with brain tumours in the posterior
      fossa (n = 25) or cerebral hemispheres (n = 10). Assessments were made before (n
      = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation
      (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first
      order derivatives (FOD) and mean concentrations were determined from the GH
      profiles taken after neurosurgery but before radiotherapy (n = 16) and in three
      treatment groups: Group 1: neurosurgery only without DXR (n = 9); Group 2: > or =
      30 Gy DXR only (n = 22); Group 3: > or = 30 Gy DXR with additional chemotherapy
      (n = 9). Results were compared with those from 26 short normally growing (SN)
      children. Compared with SN children, children with brain tumours had faster GH
      pulse periodicities (200 min vs 140 min) and attenuated peak GH responses to ITT
      (24.55 (19.50-30.20) vs 8.32 (4.57-15.14) mU/l) after neurosurgery, before
      radiotherapy. However, spontaneous GH peaks (19.05 (15.49-23.44) vs 14.13 (9.12
      21.38) mU/l), 24 h mean GH (5.01 (4.37-5.62) vs 3.98 (2.63-5.89) mU/l) and FODs
      (1.43 (1.17-1.69) vs 1.22 (0.88-1.56) mU/l per min) were similar. The
      abnormalities present before radiotherapy persisted in group 1 children at 1 year
      when 24 h mean GH (2.45 (1.17-5.01) mU/l) and FODs (0.73 (0.26-1.20) mU/l per
      min) were additionally suppressed, although partial recovery was evident by 2
      years. With time from radiotherapy, there was a progressive increase in GH pulse
      periodicity (Group 2: 200 min at 1 year, 240 min at > or = 2 years; Group 3: 140
      min at 1 year, 280 min at > or = 2 years) and a decrease in 24 h mean GH (Group 2
      vs Group 3 at > or = 2 years: 2.45 (1.70-3.47) vs 1.86 (1.32-2.69) mU/l) and FODs
      (Group 2 vs Group 3 at > or = 2 years; 0.56 (0.44-0.69) vs 0.44 (0.27-0.61) mU/l
      per min). Initial discrepancies between measures of spontaneous and stimulated
      (ITT) GH peaks were lost by 2 or more years (spontaneous vs ITT; Group 2: 7.76
      (5.89-9.77) vs 3.80 (0.91-15.84) mU/l; Group 3: 6.03 (4.27-8.32) vs 3.80 (0.31
      46.77) mU/l). After cranial irradiation, a number of changes evolved within the
      GH axis: faster GH pulse periodicities and discordance between physiological and
      pharmacological tests of GH secretion before irradiation gave way to a slow GH
      pulse periodicity, decreased GH pulse amplitude and rate of GH change (FOD) and,
      with time, eventual concordance between physiological and pharmacological
      measures. The evolution of these disturbances may well reflect differential
      pathology affecting hypothalamic GH-releasing hormone and somatostatin.

PMID- 8869598
TI  - 8-Bromo-cAMP inhibits glucose transport activity in mouse placental cells in
      culture.
AB  - Glucose plays an important role in fetal development and energy metabolism.
      Facilitative glucose transporter-1 (GLUT1) has been found in placenta. However,
      little is known about GLUT1 modulation in placental cells. To examine changes in
      mouse placental GLUT1 levels caused by 8-bromo-cAMP, we performed 2-deoxyglucose
      uptake experiments, Northern blot analysis and immunoblot analysis using a
      primary mouse placental cell culture. Immunohistochemical analysis showed that
      GLUT1 was localized to the ectoplacental cone and the labyrinth zone of mouse
      placentas on days 7 and 11 of pregnancy respectively. Treatment of mouse
      placental cells with 250 mumol/l 8-bromo-cAMP resulted in a significant (P <
      0.01) decrease in glucose uptake on days 2-5 of culture. The inhibitory effect of
      8-bromo-cAMP on glucose uptake was concentration-dependent. Glucose uptake was
      also inhibited by 100 micrograms/l cholera toxin and by 0.1 mmol/l forskolin.
      Northern blot and immunoblot analysis revealed that both GLUT1 mRNA and protein
      levels were also decreased by 8-bromo-cAMP. These findings suggest that 8-bromo
      cAMP inhibits glucose transport activity in mouse placental cells in culture.

PMID- 8869600
TI  - Inter-relationships between nonapeptide hormones and cyclic nucleotides within
      cultured porcine granulosa cells.
AB  - The reciprocal control of nonapeptide hormone (oxytocin, vasopressin) and cyclic
      nucleotide (cAMP, cGMP) release by porcine granulosa cells was studied. In
      particular, the influence of vasopressin and oxytocin treatment (10-10 000 ng/ml)
      on basal and LH-induced cAMP and cGMP output, as well as the effects of dibutyryl
      cAMP (dbcAMP; cAMP analogue) and forskolin (a stimulator of cAMP formation; 0.1
      1000 ng/ml) on vasopressin and oxytocin secretion by cultured porcine granulosa
      cells were examined. It was observed that the addition of arginine-8-vasopressin
      or oxytocin stimulated both cAMP and cGMP output from granulosa cells. Moreover,
      both vasopressin and oxytocin also increased LH-stimulated cAMP and cGMP release.
      On the other hand, both dbcAMP and forskolin decreased vasopressin secretion.
      Oxytocin release was stimulated under the influence of dbcAMP. The same
      stimulating effect occurred with forskolin given at a low dose (1 ng/ml), whilst
      higher doses of forskolin (10 or 1000 ng/ml) were inhibitory. The present
      observations demonstrate the reciprocal influence of nonapeptide hormones and
      cyclic nucleotides in porcine ovarian cells. Oxytocin and vasopressin, like LH,
      exert their action on the ovary via the activation of cAMP- and cGMP-dependent
      intracellular mechanisms. cAMP in turn inhibits vasopressin release through a
      negative feedback mechanism. On the other hand, a reciprocal stimulation of
      oxytocin and cAMP output in granulosa cells is suggested. Thus, cyclic
      nucleotides can be both regulators of nonapeptide hormone secretion and mediators
      of their action within porcine ovaries.

PMID- 8869601
TI  - The first Garnett Passe and Rodney Williams memorial lecture: has the specialty
      of ENT-head and neck surgery a future?

PMID- 8869602
TI  - The history of percutaneous tracheotomy.
AB  - Percutaneous tracheotomy is a surgical procedure for inserting a tracheal cannula
      into the tracheal lumen without a large incision, without extensive dissection of
      pretracheal tissue and without exposure of the trachea. Ciaglia's report on the
      procedure a decade ago led to this technique gaining popularity, although its
      origin is much older.

PMID- 8869603
TI  - Problems in assessing the audiogram in patients with severe hearing impairment.
AB  - Severe hearing impairment (SHI) is an impairment of hearing in which the air
      conduction mean over 0.5-4 kHz in the better hearing ear lies between 70 and 90
      dB. Masking of bone and air conduction thresholds is seldom possible with SHI,
      leading to difficulties in assessing the pure tone audiogram whenever there is a
      potential air bone gap in either ear. An audiological survey of 83 patients with
      severe hearing impairment was conducted. In 16 per cent of patients there was no
      possibility of a material air bone gap in either ear and no difficulty in
      interpreting the audiogram. In 23 (28 per cent), the audiogram was consistent
      with, but did not prove the presence of, an air bone gap in the poorer hearing
      ear. In 25 patients (30 per cent of 108) the better hearing ear could not be
      determined, and in 22 (27 per cent) a profound sensorineural impairment in the
      poorer hearing ear could not be excluded. The implications of this for the
      otologist are discussed.

PMID- 8869604
TI  - A comparison of partial inferior turbinectomy and cryosurgery for hypertrophic
      inferior turbinates.
AB  - A variety of surgical procedures are performed for treatment of hypertrophic
      inferior turbinates, but there is no completely effective therapy. We evaluated
      subjectively and objectively 52 patients who underwent one of two procedures:
      partial inferior turbinectomy (PIT) or cryosurgery of the inferior turbinates
      (CS). The results of PIT showed good functional results in 77 per cent of cases
      for long-term effectiveness. The results of CS showed that effectiveness was
      reduced from a 62 per cent success rate after one year to 35 per cent later, but
      CS was a simple procedure which was performed on an outpatient basis with no post
      operative morbidity.

PMID- 8869605
TI  - A survey to determine the extent of previous symptoms and surgery on patients
      presenting with nasal polyps.
AB  - The aim of our study was to investigate the prevalence of surgery on the nose
      prior to first time diagnosis of nasal polyps. We interviewed 60 patients who
      presented to the ENT Department at the Royal South Hants Hospital Southampton and
      were diagnosed as suffering from nasal polyps for the first time. Patients who
      suffered from cystic fibrosis or known primary ciliary dyskinesia were excluded.
      The average length of time of nasal blockage as the main symptom prior to the
      diagnosis of nasal polyps was less than two years. Out of the 60 patients six (10
      per cent) had had previous nasal surgery. Out of these six patients, only four
      patients had a previous procedure on the nose that could be considered to be
      related to the later diagnosis of nasal polyps. Only one patient had had
      radiological investigation of his sinuses in the past. We conclude that polypoid
      nasal disease is a de novo diagnosis with a relatively short history in the
      majority of patients and not preceded by a long history of ENT investigations nor
      surgery on the nose.

PMID- 8869606
TI  - Reconstruction with composite nasal septal cartilage and auricular cartilage in
      extended partial laryngectomy.
AB  - Several reconstruction techniques have been employed following partial
      laryngectomy in order to improve laryngeal function. We report 12 cases in which
      composite nasal septal cartilage and auricular cartilage were used. We
      decannulated the patients in an average of 19 days. Following the reconstruction
      we obtained a satisfactory phonatory function and swallowing. Six patients
      completed a follow-up period of three years without presenting any recurrences or
      mortality. Our experience with reconstruction using composite nasal septal and
      auricular cartilage following partial laryngectomy proved effective.

PMID- 8869607
TI  - Human papillomavirus and p53 oncoprotein in verrucous carcinoma of the larynx.
AB  - The incidence of p53 antigen and human papillomavirus (HPV) expression in
      archival formalin-fixed, paraffin-embedded tissue sections from verrucous
      carcinoma of the larynx was determined using immunohistochemistry. The p53
      oncoprotein was detected in four of 10 tissue samples (40 per cent). The same
      number of tumours had HPV antigen, and three cases had both p53 oncoprotein and
      HPV antigen. All positive cases were from heavy smokers and drinkers. After
      surgical treatment, no tumour recurrence was present in our series. Four patients
      developed a second head and neck neoplasm and death occurred in three. Three of
      the patients with second tumour had p53 positive immunoreactivity and two had p53
      and HPV expression. Verrucous carcinoma of the larynx presented with
      overexpression of p53 antigen in a similar percentage to other head and neck
      cancers. The p53 immunohistochemical determination is well correlated with HPV
      detection and could have prognostic value in these tumours, but no statistical
      evidence was present.

PMID- 8869608
TI  - Experimental study on neurorrhaphy of the recurrent laryngeal nerve in dogs.
AB  - The effectiveness of anastomosis of a divided recurrent laryngeal nerve was
      evaluated in six adult mongrel dogs. Videolaryngoscopy and evoked compound muscle
      action potentials in the intrinsic laryngeal muscles were performed at six months
      and the posterior cricoarytenoid muscles and recurrent laryngeal nerves were
      processed for histomorphometric studies. Recovery of compound muscle action
      potentials in all re-innervated muscles and histomorphometric findings confirmed
      a good grade of axonal regeneration. The most significant histomorphometric
      changes observed were: a reactive hypertrophy of type I fibres in the posterior
      cricoarytenoid muscles of the re-innervated side, and a high nerve fibre density
      in the distal stump to the anastomosis. However, incomplete recovery of motion
      and fasciculated movements of the re-innervated vocal folds were observed.
      Reduction of effective motor units in the re-innervated muscles might be a factor
      that cause incomplete restoration of vocal fold movements.

PMID- 8869609
TI  - CO2 laser palatoplasty: early results.
AB  - It is now widely accepted that snoring causes significant social dysfunction. In
      the absence of obstructive sleep apnoea syndrome, palatal surgery offers a very
      good chance of eliminating or reducing snoring. The traditional operation of
      uvulopalatopharyngoplasty remains the 'gold standard', but may be complicated by
      velopharyngeal incompetence, severe post-operative pain and even nasopharyngeal
      stenosis. A newer technique to reduce snoring caused by palatal flutter by using
      a neodymnium:yttrium aluminum garnet laser to stiffen the soft palate has been
      introduced recently by another unit. We show that this procedure can be carried
      out using a CO2 laser, and present the initial results of the first 29 patients
      operated on at The Royal National Throat, Nose and Ear Hospital.

PMID- 8869610
TI  - A clinicopathological and immunohistochemical study of the calcifying epithelial
      odontogenic tumour (Pindborg tumour) in Malaysians.
AB  - We reviewed the clinicopathological characteristics of 13 cases of calcifying
      epithelial odontogenic tumour (CEOT) (Pindborg tumour) diagnosed in the Division
      on Stomatology, Institute for Medical Research, Kuala Lumpur, over a 29-year
      period. There were eight female and five male patients. These consisted of eight
      (61.5 per cent) Malays, three (23.1 per cent) Chinese, one (7.7 per cent) Indian
      and one (7.7 per cent) Melanau. Their ages at presentation ranged from 19-61
      years (mean age, 31.8 years). There were 12 central and one peripheral CEOT. Of
      these, 76.9 per cent of cases were located in the maxilla, the remaining in the
      mandible. The commonest clinical diagnosis was a dentigerous cyst (66.7 per
      cent). Enucleation was the main mode of treatment. Histologically, sheets and
      strands of polyhedral epithelial cells containing eosinophilic, homogeneous
      globules with Liesegang rings were observed. One case also showed extensive
      calcification and clear cell differentiation. Immunohistochemistry revealed a
      variable keratin staining of the CEOT epithelium, confirming its heterogeneity.

PMID- 8869612
TI  - Electrodissection tracheotomy.
AB  - The acquired immune deficiency syndrome (AIDS) epidemic and other potentially
      fatal blood-borne infectious diseases have produced a heightened awareness for
      preventing accidental inoculation of surgeons and operating theatre staff. It is
      incumbent upon the head and neck surgeon to use safe and effective surgical
      technique in these patients to prevent such an event. We are seeing an increasing
      number of patients with AIDS and hepatitis undergoing tracheotomy. We present a
      sharps-free technique for tracheotomy which is safe for the hospital staff and
      the patient.

PMID- 8869611
TI  - Maxillary antral lavage using inferior meatal cannula anaesthesia.
AB  - Antral puncture and lavage through the inferior meatus is a minor but common
      otolaryngological procedure, usually performed under local anaesthesia. We
      describe a new method of introducing local anaesthetic into the inferior meatus,
      via the use of a soft intravenous cannula connected to a syringe containing 10
      per cent cocaine paste. We have called this new technique inferior meatal cannula
      anaesthesia (IMCA).

PMID- 8869613
TI  - Pseudocyst of the auricle: a new method of treatment.
AB  - Pseudocyst of the auricle is a condition where spontaneous serous fluid
      collection is seen on the lateral surface of the pinna. The aetiology of this
      condition is not known. Several methods of treatment have been advocated in the
      past. We report 10 cases of unilateral pseudocyst who were treated with
      aspiration and pressure dressing by a plaster of Paris cast over the pinna for
      two weeks.

PMID- 8869614
TI  - Malignant otitis externa in HIV and AIDS.
AB  - Malignant otitis externa is a necrotising infection of the external ear canal
      which may spread to include the mastoid and petrous parts of the temporal bone,
      leading to skull base osteomyelitis. It is almost exclusively caused by infection
      with Pseudomonas aeruginosa, and usually occurs in elderly non-insulin-dependent
      diabetic patients. However isolated cases have been reported in a small number of
      non-diabetic patients, particularly in children who are immunocompromised due to
      malignancy, malnutrition and severe anaemia. In 1984 a case of malignant otitis
      externa was reported in a child with an acquired immunodeficiency syndrome (AIDS)
      like illness, prior to identification of the human immunodeficiency virus (HIV).
      Since that time further sporadic cases of this invasive infection have been
      reported in HIV and AIDS. We present two further cases and also a review of the
      current literature.

PMID- 8869615
TI  - Bilingual hearing acquisition in Welsh and English following cochlear
      implantation.
AB  - A post lingually deafened adult equilingual in Welsh and English, receive
      rehabilitation in both languages following cochlear implantation. Hearing
      acquisition was very similar in both languages, indicating that there is no need
      to vary the electrode coding strategy for different languages of Indo-European
      origin. The situation may be difficult for tonal languages such as Chinese.

PMID- 8869616
TI  - Post-irradiation liposarcoma of the temporal bone.
AB  - The first reported case of liposarcoma of the temporal bone is presented. Its
      association with previous irradiation for benign parotid disease is discussed.

PMID- 8869617
TI  - Cowpox infection of the nose.
AB  - A case of cowpox infection presenting as a necrotising cellulitis of the nasal
      tip and vestibule is reported. Diagnosis was established by identification of the
      pox virus particles from tissue culture of the nasal biopsy using electronic
      microscopy and the characteristic lesions on chorio-allantoic membrane produced
      by the virus. Cowpox of the external nose and transmission of the infection from
      a dog have not to our knowledge been reported previously.

PMID- 8869618
TI  - Paraffinoma revisited: a post-operative condition following rhinoplasty nasal
      packing.
AB  - Paraffin impregnated tulle is frequently used as a post-operative dressing after
      surgical repair of wounds, on skin-donor sites and in packing of tissue cavities.
      Historically, paraffin has been injected into various sites of the body and
      paraffinoma is a well-described complication. Despite this, nasal packing with
      paraffin gauze is still common after rhinoplasty. We report a case of paraffinoma
      occurring after rhinoplasty and discuss the avoidance of this rare but serious
      complication and suggest silicon mesh as an alternative dressing.

PMID- 8869619
TI  - Mass in the post nasal space and acquired immune deficiency syndrome.
AB  - We report a case of previously undiagnosed acquired immunodeficiency syndrome
      (AIDS) who had a mass in the post-nasal space causing almost complete nasal
      obstruction. Histology showed both respiratory and squamous epithelium covering
      an active chronic inflammatory infiltrate. Lymphoma, Kaposi's sarcoma and
      infiltrative fungal sinusitis were excluded. There was no evidence of the common
      viruses associated with lesions in AIDS. Unlike adenoid hypertrophy, the lesion
      was an exuberant growth with an additional chronic inflammatory reaction due to
      ulceration of the surface epithelium.

PMID- 8869620
TI  - Invasive candidiasis of a late presentation laryngeal chondroradionecrosis.
AB  - Laryngeal chondroradionecrosis is an unusual condition which may present many
      years after the initial radiotherapy. We present a case of late onset
      chondroradionecrosis which was complicated by invasive candidiasis of the
      arytenoid cartilages which had themselves been extruded through the laryngeal
      mucosa.

PMID- 8869621
TI  - Foreign body in the throat migrating through the common carotid artery.
AB  - We present a 55-year-old lady who swallowed a 3 cm pointed metal foreign body
      whilst eating a sardine salad. The foreign body migrated from the hypopharynx
      through the parapharyngeal space and traversed the common carotid artery over a
      period of 12 days. The foreign body was removed by exploration of the neck.

PMID- 8869622
TI  - An unusual cause of facial pain.
AB  - A case of chronic facial pain and headache is presented. This was found to be due
      to two pieces of windscreen-glass lodged in the superior meatus of the patient's
      nose since a road-traffic-accident 14 years earlier. Despite being reported as
      normal, review of previous X-rays of her sinuses showed that the glass was
      visible. The importance of carefully assessing the intranasal area on sinus-views
      is illustrated.

PMID- 8869623
TI  - Facial paralysis caused by a lymphoepithelial cyst located in the parotid gland.
AB  - We report the case of an acute onset facial paralysis which was caused by a
      benign lymphoepithelial cyst found in the parotid, an association which is a
      rarity in the literature. The diagnosis and surgical management is discussed.
      This report emphasises the clinical principle that parotid masses causing an
      acute facial palsy are not necessarily malignant in nature. Intra-operative
      frozen section histology is helpful in saving the patient from unnecessarily
      radical surgery.

PMID- 8869624
TI  - Wegener's granulomatosis presenting as a temporal headache.
AB  - Formerly a fatal condition, Wegener's granulomatosis is now treated with good
      results. Clinical morbidity is often due to failure by clinicians to make the
      diagnosis. Many patients (including our cases reported here) present with
      atypical symptoms, and only a high index of suspicion will ensure early
      diagnosis. Classical chest and renal symptoms often indicate late stage disease.
      We present two cases that underline the limitations of current 'diagnostic'
      immunological tests whilst emphasising the importance of clinical features in
      diagnosis. Standard treatment with Cytotoxic agents and corticosteroids are
      effective but carry considerable morbidity. We have followed the current trend of
      incorporating a less toxic antibiotic agent in the management of this enigmatic
      condition.

PMID- 8869625
TI  - Intestinal-type sinonasal adenocarcinoma: a sporadic case.
AB  - A sporadic case of the intestinal-type sinonasal adenocarcinoma is described. The
      patient was a comparatively young 33-year-old woman employed as a senior
      biochemical scientific technologist for several years. The light microscopical
      pattern was that of a papillary-tubular adenocarcinoma with areas of more solid
      mucinous elements in the deeper parts of the neoplasm. The neoplasm had invaded
      the nasal septum and reached the left orbit invading the left ethmoidal sinus.
      The glands were lined by columnar cells with elongated spindle-shaped nuclei and
      the cells expressed cytokeratin, carcinoembryonic antigen (CEA), Chromogranin A,
      gastrin and serotonin but not neurone-specific enolase (NSE) nor synaptophysin.
      Neurosecretory granules were present. There was no history of wood dust
      inhalation and her exposure to chemicals is of some interest but had probably
      little or no role in the causation of this neoplasm.

PMID- 8869626
TI  - T-cell-rich histiocyte-rich B-cell lymphoma of parotid gland.
AB  - We describe a malignant lymphoma of the parotid gland arising in a patient with
      Sjogren's syndrome. Diagnosis was established on needle biopsy which showed a
      mixed population of lymphoid cells. Immunohistochemistry revealed B-lymphoid
      cells, T-lymphoid cells and histiocytes. Clonal immunoglobulin heavy chain gene
      rearrangement was demonstrated using the polymerase chain reaction. Within the
      confines of the small biopsy, the lesion qualifies for the designation T-cell
      rich histiocyte-rich B-cell lymphoma. The value of molecular techniques in the
      diagnosis of malignant lymphoma on limited tissue samples is highlighted by this
      case.

PMID- 8869627
TI  - Laser surgery in the UK-a consultant survey.

PMID- 8869628
TI  - Body experience differences of women with preterm labor.
AB  - PROBLEM: To determine whether body changes described and evaluated by women with
      preterm labor differed from those of women with normal pregnancies. METHODS:
      Experiences of weight, appetite, activity, and mood change experiences for four
      sequential time intervals of pregnancy from 41 women with preterm labor and 23
      women with normal pregnancies were analyzed using log-linear procedures.
      FINDINGS: The pregnancies of women with preterm labor were characterized by
      greater frequencies of worrisome body changes up until the 28th week. CONCLUSIONS
      & IMPLICATIONS FOR NURSING: Preterm labor was discussed as a problem of body
      image organization. Women with preterm labor have greater difficulty assimilating
      and accommodating to the body changes of pregnancy. A model of body change for
      preterm labor pregnancy was described. Study findings emphasized the importance
      of psychoemotional phenomena in preterm labor childbearing outcomes.

PMID- 8869629
TI  - Multidisciplinary research of multimodal stimulation of premature infants: an
      integrated review of the literature.
AB  - PURPOSE: To review and integrate current multidisciplinary research literature
      about multiple sensory stimulation of premature infants. SOURCES: Computer search
      using CINAHL, MEDLINE, PSYLIT, SOCIAL SCIENCE INDEX and the topics "premature,"
      "infant," "neonate," and "stimulation." Review of the results of the research and
      integration of findings for nursing. RESULTS: Overall, infants responded
      positively to the interventions reviewed, including immediate and long-term
      effects, some up to 2 years. IMPLICATIONS FOR NURSING PRACTICE: Nursing research
      of multiple sensory stimulation of premature infants can be improved by the use
      of (a) a theoretical base for research, (b) better descriptions of the infant
      samples and the environmental context of the research, and (c) individualization
      of infant stimulation to permit conservation of epigenetic integrity of the
      infant.

PMID- 8869630
TI  - Evaluation of an intergenerational program for pregnant and parenting
      adolescents.
AB  - PROBLEM: Poor life outcomes for teenage mothers SUBJECTS: Young mothers (N = 65)
      several years after the birth of their first child. Half had mothers (called
      grandmothers) who attended the Teenage Mothers-Grandmothers program. METHODS: A
      long-term evaluation study of the effects of the Teenage Mothers-Grandmothers
      Program on outcomes for the teens. Instruments used: demographic questionnaire,
      the Rosenberg Self-Esteem Scale, the Arizona Social Support Inventory Schedule,
      and an open-ended questionnaire. FINDINGS: Teens whose mothers participated in
      the program were significantly less likely to drop out of school and had
      significantly better self-esteem. CONCLUSIONS & IMPLICATIONS FOR NURSING:
      Including the mothers of pregnant and parenting adolescents in programs can be
      beneficial.

PMID- 8869631
TI  - The evolution of sugar isomerases.
AB  - L-Arabinose isomerase (EC 5.3.1.4) catalyzes the isomerization of L-arabinose to
      L-ribulose. Here we report on the purification, kinetic mechanism and chemical
      mechanism of L-arabinose isomerase from Escherichia coli. The enzyme catalyzes
      the isomerization of L-arabinose to L-ribulose by a proton transfer mechanism, in
      contrast to xylose isomerase which uses a hydride transfer mechanism to perform a
      similar isomerization. Arabinose isomerase activity is metal dependent, although
      the enzyme can catalyze the exchange of the proton attached to carbon 2 of
      arabinose with the solvent in the absence of metal ion. Manganese(II) is the only
      metal ion which renders the enzyme active for the isomerization reaction.
      Arabinose isomerase has high substrate specificity for L-arabinose. The
      difference in chemical mechanism between xylose isomerase and arabinose isomerase
      suggests that these enzymes are not related by convergent evolution. This work
      also suggests that unless convergent evolution has been demonstrated, the
      mechanism of one enzyme may not give any insight into the mechanism of a second
      enzyme catalyzing the same reaction.

PMID- 8869632
TI  - Protein fold recognition by threading: comparison of algorithms and analysis of
      results.
AB  - Optimal sequence threading can be used to recognize members of a library of
      protein folds which are closely related in 3-D structure to the native fold of an
      input test sequence, even when the test sequence is not significantly homologous
      to the sequence of any member of the fold library. The methods provide an
      alignment between the residues of the test sequence and the residue positions in
      a template fold. This alignment optimizes a score function, and the predicted
      fold is the highest scoring member of the library of folds. Most score functions
      contain a pairwise interaction energy term. This, coupled with the need to
      introduce gaps into the alignment, means that the optimization problem is NP
      hard. We report a comparison between two heuristic optimization algorithms used
      in the literature, double dynamic programming and an iterative algorithm based on
      the so-called frozen approximation. These are compared in terms of both the
      ranking of likely folds and the quality of the alignment produced.

PMID- 8869633
TI  - Designing amino acid sequences to fold with good hydrophobic cores.
AB  - We present two methods for designing amino acid sequences of proteins that will
      fold to have good hydrophobic cores. Given the coordinates of the desired target
      protein or polymer structure, the methods generate sequences of hydrophobic (H)
      and polar (P) monomers that are intended to fold to these structures. One method
      designs hydrophobic inside, polar outside; the other minimizes an energy function
      in a sequence evolution process. The sequences generated by these methods agree
      at the level of 60-80% of the sequence positions in 20 proteins in the Protein
      Data Bank. A major challenge in protein design is to create sequences that can
      fold uniquely, i.e. to a single conformation rather than to many. While an
      earlier lattice-based sequence evolution method was shown not to design unique
      folders, our method generates unique folders in lattice model tests. These
      methods may also be useful in designing other types of foldable polymer not based
      on amino acids.

PMID- 8869634
TI  - Use of a model to understand prolactin and growth hormone specificities.
AB  - A human prolactin (hPRL) model based on a 2.1 A resolution X-ray refinement of
      porcine growth hormone is reported. Only regions clearly defined in the growth
      hormone template (the four-helix bundle) or previously assumed to be involved in
      hPRL-receptor binding (the bundle and the binding site loop) are included. A
      description of the model construction is provided and the resulting hPRL
      structure is used to interpret mutation/activity data for the cross-reactivity of
      human growth hormone (hGH) with the lactogenic receptor and the binding of human
      and bovine prolactin to the lactogenic receptor. The recognition of hPRL by its
      receptor unexpectedly appears to resemble more closely the interaction of hGH
      with the somatogenic receptor than with the lactogenic receptor. Each hGH binds
      to two receptor molecules, and an essential second messenger mediated by correct
      formation of the receptor-receptor interface has been proposed. The absence of
      receptor cross-reactivity for hPRL is linked to key sequence changes in hPRL
      which could disrupt hPRL-somatogenic receptor binding at the second site. A
      number of previous experiments have relied on the assumption that bioactivity is
      mediated by homologous residues at topologically equivalent positions. According
      to the model, this does not appear to be strictly true at either binding site.
      Good correlation at equivalent positions may be restricted to residues that are
      important for maintaining binding site shape as well as providing complementary
      stabilizing interactions between the hormone and receptor. Experiments are
      proposed to test our hypotheses.

PMID- 8869635
TI  - Model complexes of tumor necrosis factor-alpha with receptors R1 and R2.
AB  - The biological activities of tumor necrosis factor-alpha (TNF-alpha) are mediated
      by two different receptors, TNFR1 and TNFR2. To analyze the receptor binding
      site(s) of TNF-alpha, molecular models have been built of the complexes of TNF
      alpha with the extracellular regions of receptors R1 and R2, based on the known
      crystal structures of TNF-alpha and lymphotoxin bound to R1. The model structure
      of R2 from residues 18-160 was built by analogy to the crystal structure of R1 in
      complex with lymphotoxin. The amino acid sequences of R1 and R2 show 27.5%
      identity over this region and were aligned with five insertions and three
      deletions. There are 18 conserved cysteines that form disulfides. R2 has lost one
      pair of cysteines compared with R1, but two new cysteines were modeled as forming
      a new disulfide bond. Both symmetric and asymmetric trimers of TNF-alpha were
      used to model the complexes with TNFR1 and R2. An analysis of differences in the
      model complexes showed good agreement with data on the differential binding of
      TNF mutants to its two receptors.

PMID- 8869636
TI  - A model for vicilin solubility at mild acidic pH, based on homology modelling and
      electrostatics calculations.
AB  - The crystallographic structures of jack bean canavalin and French bean phaseolin
      have been used to construct a homology model of the storage vicilin of cocoa.
      Reported molecular weights for cocoa storage protein subunits correlate with
      proteolysis at the site of a large hydrophilic insert in the mature protein.
      Burial of the hydrophobic amino acids on trimer formation is a strongly conserved
      feature in the vicilin family. Histidine residues also sit at the monomer-monomer
      interfaces of the trimer and are likely to contribute to the decreased solubility
      of cocoa vicilin at mild acidic pH, which is generally considered to be caused
      solely by aggregation near to the isoelectric point. Electrostatic calculations
      suggest that such an arrangement of histidine residues in the absence of specific
      counterion binding will not favour the particular geometry of trimer formation
      below neutral pH. Higher order aggregates that do not exclude histidine charge
      from the solvent may be favoured, aiding the precipitation of cocoa vicilin at
      mild acidic pH. This suggestion is considered for the vicilin family. The
      hypothesis could contribute to an understanding of the pH and ionic strength
      dependence of vicilin solubility in vitro, and possibly of the behaviour of
      vicilins in the seed storage environment.

PMID- 8869637
TI  - Comparative modeling of the three CP modules of the beta-chain of C4BP and
      evaluation of potential sites of interaction with protein S.
AB  - A computer model of the beta-chain of C4b-binding protein (C4BP) was constructed,
      using the backbone fold of the NMR structures of the sixteenth CP module of
      factor H (H16) and of a pair of modules consisting of the fifteenth and sixteenth
      CPs of factor H (H15-16). The characteristic hydrophobic core responsible for
      dictating the three-dimensional structure of the CP family is conserved in the
      amino acid sequence of C4BP beta 1, beta 2 and beta 3. The distribution of the
      electrostatic potential shows that the model is mainly covered by a negative
      contour. Interestingly, a positive area is observed in the C-terminal region of
      the first CP module, enclosing peptide 31-45, known to be a binding site for
      protein S. This observation suggests that electrostatic interactions can be of
      importance for the interaction of C4BP to protein S. A solvent-accessible
      hydrophobic patch, located nearby and involving the peptide 31-45, was also found
      in the model, further confirming that this area is involved in the interaction
      with protein S. The contribution of beta-chain residues 31-45 to the affinity for
      protein S was studied further by means of synthetic mutant peptides. The results
      suggest that both electrostatic and hydrophobic interactions are important for
      the binding to protein S.

PMID- 8869638
TI  - Residues important for the function of a multihelical DNA binding domain in the
      new transcription factor family of Cam and Tet repressors.
AB  - We report that some prokaryotic repressors including CamR and TetR belong to the
      same family. CamR and TetR bind to DNA using a multihelical DNA binding domain
      (DBD) at the N-termini of the proteins, while the C-termini are important for
      regulating the DNA binding in a manner dependent on their co-factors (camphor for
      CamR, tetracycline for TetR). In all, 11 important amino acid positions have been
      identified in the CamR DBD by the systematic substitution of residues by Ala. Of
      the 11 positions, 10 are either buried in the core, and thus important for
      creating the hydrophobic environment, or exposed on the surface, and thus
      important for binding to DNA. The eleventh residue, Gly, seems to be important
      for a loop structure. The DNA binding mode of this type of DBD and a general
      mechanism of regulating their DNA binding are discussed in reference to the
      crystal structure of TetR [Hinrichs et al., (1994) Science, 264, 418-420].

PMID- 8869639
TI  - Site-directed mutagenesis of Arg58 and Asp86 of elongation factor Tu from
      Escherichia coli: effects on the GTPase reaction and aminoacyl-tRNA binding.
AB  - Elongation factor Tu from Escherichia coli was mutated separately at positions
      Asp86 and Arg58, in order to shed light both on the GTPase mechanism of
      elongation factor Tu and on the binding of aminoacyl-tRNA. In addition, the
      binding of guanine nucleotides was investigated by determination of the
      dissociation and association rate constants. The results imply that Arg58 is
      unimportant for the intrinsic GTPase mechanism and the binding of guanine
      nucleotides, whereas it is strongly involved in the binding of aminoacyl-tRNA and
      of the ribosome. Asp86 appears to be essential for the regulation of guanine
      nucleotide affinities, and it may also play a role in the intrinsic GTPase
      mechanism.

PMID- 8869640
TI  - An engineered Staphylococcus aureus PC1 beta-lactamase that hydrolyses third
      generation cephalosporins.
AB  - The beta-lactamase from Staphylococcus aureus PC1 has been cloned into an
      Escherichia coli vector for site-directed mutagenesis and high-level protein
      expression. A mutant enzyme has been produced in which Ala238 is replaced by a
      serine, and Ile239 is deleted (A238S:I239del). The engineered enzyme hydrolyses
      third-generation cephalosporins substantially more rapidly than the parental
      enzyme does, while hydrolysis of benzylpenicillin is slower with the mutant than
      with the wild-type and native enzymes. The mutant beta-lactamase has been
      crystallized and the structure determined and refined at 2.8 A resolution. The
      disposition of the beta-strand which forms the side of the active site is altered
      in comparison with the native S. aureus beta-lactamase structure, widening the
      active site cleft and providing space to accommodate the bulky side-chains of the
      third-generation cephalosporins.

PMID- 8869641
TI  - Exchange of domains of glutamate dehydrogenase from the hyperthermophilic
      archaeon Pyrococcus furiosus and the mesophilic bacterium Clostridium difficile:
      effects on catalysis, thermoactivity and stability.
AB  - The glutamate dehydrogenase gene from the hyperthermophilic archaeon Pyrococcus
      furiosus has been functionally expressed in Escherichia coli under the control of
      the lambda PL promoter. The P. furiosus glutamate dehydrogenase amounted to 20%
      of the total E. coli cell protein, and the vast majority consisted of hexamers.
      Following activation by heat treatment, an enzyme could be purified from E. coli
      that was indistinguishable from the glutamate dehydrogenase purified from P.
      furiosus. Hybrid genes, that consisted of the coding regions for the homologous
      glutamate dehydrogenases from P. furiosus and the mesophilic bacterium
      Clostridium difficile, were constructed and successfully expressed in E. coli.
      One of the resulting hybrid proteins, containing the glutamate binding domain of
      the C. difficile enzyme and the cofactor binding domain of the P. furiosus
      enzyme, did not show a detectable activity. In contrast, the complementary hybrid
      containing the P. furiosus glutamate and the C. difficile cofactor binding domain
      was a catalytically active hexamer that showed a reduced substrate affinity but
      maintained efficient cofactor binding with the specificity found in the
      Clostridium symbiosum enzyme. Compared with the C. difficile glutamate
      dehydrogenase, the archaeal-bacterial hybrid is slightly more thermoactive, less
      thermostable but much more stable towards guanidinium chloride-induced
      inactivation and denaturation.

PMID- 8869642
TI  - Domain-domain interactions in hybrids of tissue-type plasminogen activator and
      urokinase-type plasminogen activator.
AB  - Fibrin-dependent plasminogen activation by tissue-type plasminogen activator (t
      PA) is in part associated with the presence of the kringle 2 domain in t-PA.
      Within this kringle 2 domain a lysyl-binding site has been described. The
      plasminogen to plasmin conversion by urokinase-type plasminogen activator (u-PA),
      in contrast to that of t-PA, is not enhanced in the presence of fibrin. Within
      the u-PA kringle domain no lysyl-binding site is found. To study whether
      introduction of a lysyl-binding site in the u-PA kringle domain will make u-PA a
      fibrin-dependent plasminogen activator, three stretches of amino acid residues of
      the u-PA kringle domain (A28-Q33, D55-N57 and G67-V72) were substituted by three
      stretches of amino acids from the corresponding positions of the kringle 2 domain
      of t-PA (M28-K33, D55-D57 and N67-W72). These changes resulted in the creation of
      the lysyl-binding site consensus of the kringle 2 domain (K33, D55, D57, W62 and
      W72) in the u-PA kringle. However, the resulting u-PA mutant did not interact
      with lysyl-Sepharose, nor did it display fibrin-enhanced plasminogen activation
      in the presence of soluble fibrin mimic. When the kringle domain of u-PA was
      replaced by the kringle 2 domain of t-PA, similar results were obtained. The
      hybrid protein hardly interacted with lysyl-Sepharose and the plasminogen
      activation was not enhanced in the presence of fibrin mimic. However, the N
      terminal fragment isolated from this hybrid molecule (consisting of growth factor
      domain and kringle 2 domain) did interact with lysyl-Sepharose, suggesting that
      in the hybrid molecule a functional lysyl-binding site is present but not
      operational. Indeed, lysine analogue (epsilon-amino-caproic acid) sensitive
      binding of isolated t-PA kringle 2 domain to u-PA could be observed. The modified
      u-PA kringle, the wild type u-PA kringle and the kringle 2 of the u-PA hybrid
      were also placed N-terminal of the protease domain of t-PA. As expected, the t-PA
      mutant consisting of the kringle 2 domain and the protease domain bound to lysyl
      Sepharose and showed fibrin-dependent plasminogen activation. Further, the hybrid
      molecule consisting of the u-PA kringle placed N-terminal of the t-PA protease
      domain did not display these features. Introduction of the modified u-PA kringle
      N-terminal of the t-PA protease domain resulted in a very weak interaction with
      lysyl-Sepharose. Despite the high overall similarity in primary structure of the
      modified u-PA kringle and t-PA kringle 2 (68%), no fibrin-dependent plasminogen
      activation of this hybrid molecule was observed. The above-mentioned results
      question the concept that the structural auto-nomous domains within hybrid
      plasminogen activators t-PA and u-PA function as autonomous domains and suggest
      that interactions between the kringle and the protease domain in hybrid molecules
      strongly influences their functional features.

PMID- 8869643
TI  - Involvement of the NH2-terminal region of oryzacystatin-I in cysteine proteinase
      inhibition.
AB  - Cystatins are small protein inhibitors of cysteine proteinases. The relative
      importance of the N-terminal region of cystatins, and of a conserved glycine
      within this region, remains unclear despite several studies. It was found that
      deletion of the N-terminal 21 amino acids abolishes the inhibitory capacity of
      oryzacystatin-I. The importance of a conserved glycine residue (Gly10) was also
      examined by replacing it with 11 other amino acids. Three further glycine
      residues (Gly5, -6 and -11) in this N-terminal region of oryzacystatin-I were
      similarly mutated. Only those variants in which Gly10 was substituted show any
      significant change in inhibitory capacity compared with wild-type oryzacystatin
      I. The inhibitory characteristics of hybrid cystatin molecules comprising regions
      of chicken egg white cystatin and oryzacystatin were also examined. It is
      suggested that in common with animal cystatins, the N-terminal region of the
      plant cystatin, oryzacystatin-I, and in particular the highly conserved Gly10
      residue are important for effective inhibition of papain.

PMID- 8869644
TI  - Regulation of protein tyrosine phosphatase 1C: opposing effects of the two src
      homology 2 domains.
AB  - The regulatory roles of the two src homology 2 (SH2) domains of protein tyrosine
      phosphatase 1C were investigated by comparing recombinant full-length PTP1C with
      mutants in which either the N-terminal SH2 (N-SH2) domain (PTP1C delta NSH2), the
      C-terminal SH2 (C-SH2) domain (PTP1C delta CSH2) or both SH2 domains were deleted
      (PTP1C delta NSH2 delta CSH2). This revealed that the SH2 domains have opposing
      and independent effects on activity: strong inhibition by N-SH2 (42-fold) and
      weak activation by C-SH2 (2.1-fold). C-SH2 caused activation across a wide pH
      range while N-SH2 inhibited most at neutral and high pH through a shift of the
      basic limb of the pH profile of kcat/Km, apparently via perturbation of an active
      site pKa value. A phosphotyrosyl peptide derived from the erythropoietin receptor
      caused an approximately 30-fold activation of PTP1C and PTP1C delta CSH2 but had
      no effect on PTP1C delta NSH2 or PTP1C delta NSH2 delta CSH2, indicating that
      binding of this peptide to N-SH2 abolished its inhibition. Since C-SH2 separates
      N-SH2 from the catalytic domain in full-length PTP1C and activation is observed
      for PTP1C delta CSH2, it appears that the inhibitory effect of N-SH2 is
      independent of the position in the sequence and that intermolecular interactions
      may also be possible.

PMID- 8869645
TI  - Genetic construction and characterization of the diphtheria toxin-related
      interleukin 15 fusion protein DAB389 sIL-15.
AB  - A gene fusion encoding DAB389 sIL-15 was constructed in which the catalytic and
      transmembrane domains of native diphtheria toxin (DAB389) are genetically linked
      to the N-terminus of simian interleukin 15 (sIL-15). It was demonstrated that the
      cytotoxic action of DAB389 sIL-15 is mediated through the IL-15 receptor. Since
      toxicity may be blocked with chloroquine, it was concluded that following binding
      to the IL-15 receptor, the fusion toxin is internalized by receptor-mediated
      endocytosis and must pass through an acidic compartment in order to facilitate
      the delivery of the catalytic domain to the cytosol of target cells. As a non
      toxic control, the ADP-ribosyltransferase defective mutant DA(E149S)B389 sIL-15
      was constructed. It was demonstrated that both sIL-15 and DA(E149S)B389 sIL-15
      stimulate protein and DNA synthesis in IL-15 receptor-positive CTLL-2 cells in
      vitro.

PMID- 8869646
TI  - Disulfide stabilization of antibody Fv: computer predictions and experimental
      evaluation.
AB  - Using molecular modeling technology we have recently identified positions in
      conserved framework regions of Fvs which can be used to stabilize antibody Fvs by
      an interchain disulfide bond engineered in between the structurally conserved
      framework positions of the variable domains of heavy (VH) and light (VL)
      immunoglobulin chains (disulfide-stabilized Fv; dsFv). The computer model
      indicated the existence of other potential sites in the framework regions that
      might be suitable for disulfide bond formation between VH and VL. The possibility
      of obtaining dsFvs using these positions is evaluated here experimentally by
      constructing dsFv immunotoxins in which the Fv moiety is fused to a truncated
      form of Pseudomonas exotoxin. We analyzed the extent of dsFv formation and the
      activity of the resulting dsFv immunotoxins, and compared various dsFv molecules
      with the scFv immunotoxin. Our results demonstrate that position H44-L105 is the
      only one which gives high production yields of active dsFv. All other positions
      gave either low yields and activity or completely failed to produce active dsFv.
      With one exception, the formation and activities of the dsFvs corresponded to the
      C alpha-C alpha distance between the VH and VL positions, with an optimal
      distance of 5.7 A producing the best dsFv. Distances of 6.0-6.9 A resulted in a
      low yield of protein that was still capable of binding antigen, whereas distances
      > 7.0 A resulted in molecules in which dsFv formation was not obtained.

PMID- 8869647
TI  - [Post-anesthesia recovery. How can it be evaluated?].

PMID- 8869648
TI  - [Comparison of 2 systems for continuous intraoperative monitoring of oxygen
      saturation in the jugular bulb].
AB  - OBJECTIVE: To compare accuracy, precision and stability of two jugular venous
      blood catheters for continuous monitoring of oxygen saturation during surgery, in
      a nonrandom, prospective sample. PATIENTS AND METHODS: We studied 47 patients
      requiring continuous monitoring of SjvO2 during a variety of neurosurgical
      procedures. Swan-Ganz pediatric 5.5F catheters (Opticath P575-EH) were used in 27
      patients; neonatal umbilical artery 4F catheters (Opticath U425C) were used in
      20. Both catheters were equipped with a fiberoptic system for continuous
      monitoring of hemoglobin oxygen saturation. After checking correct placement,
      readings transmitted were compared with co-oximetry readings for a sample taken
      from the distal end of the catheter. We also compared time spent placing the
      catheters and stability of SjvO2 reading during surgery. RESULTS: Insertion time
      (+/- SD) was 10.3 +/- 2.5 minutes for the 4F catheter and 15.9 +/- 5.5 minutes
      for the 5.5F model (p < 0.01). Although both systems tended to overestimate, the
      5.5F catheters were more accurate: the mean differences were -6.8% for the 4F
      catheter and -1.2% for the 5.5F. These results made it necessary to calibrate the
      4F catheters after placement and before use, a procedure not needed if the 5.5F
      catheters are used. Stability of SjvO2 readings during surgery was significantly
      greater (p < 0.01) for the 5.5F catheters, such that only 25.9% were considered
      clinically useful based on this parameter. However, 70% of the 5.5F catheters
      provided acceptable SjvO2 readings. Intracranial pressure during insertion and
      removal of the SjvO2 catheters was measured in only 5 patients; there were no
      changes greater than 1 mmHg. CONCLUSIONS: Although the 5.5F pediatric catheters
      take longer to put into position, their greater accuracy, precision and stability
      makes them preferable to the 4F catheters for continuous monitoring of SjvO2.
      Long-term vascular effects must be studied further.

PMID- 8869649
TI  - [Utilization of a post-anesthetic recovery index].
AB  - OBJECTIVES: 1. To introduce use of the postanesthesia recovery score (assessing
      consciousness, mobility, ventilation, hemodynamics and blood analysis) as a good
      method for evaluating and classifying recovery from anesthesia in the
      postoperative care unit. 2. To determine overall patient progress and assess the
      influence of various patient, anesthetic and surgical factors. PATIENTS AND
      METHODS: This was a multicenter study of 1,227 patients. We excluded all patients
      who were to be transferred to intensive care units after surgery. A score of 10
      or more, with no single item score equal to 0, was considered optimal for
      discharge from the postanesthesia care unit. RESULTS: The lowest score upon
      admission to the unit was among patients who had undergone high abdominal surgery
      (16.4%). Scores over 9 belonged to patients who had undergone lower abdominal and
      perineal surgery (87.5 and 95.3%, respectively). Scores were < or = 9 in patients
      who received inhaled anesthetics (42%). Intravenous anesthesia patients (84.4%)
      had scores over 9. The local-regional anesthetic procedures with the best scores
      were axilar blocks and local infiltrations. Patients staying longer in the
      recovery unit were those classified as ASA III, those whose procedures lasted
      longer than 120 minutes, those undergoing surgery on the upper abdomen or on
      extremities, those receiving isoflurane and pancuronium, and those suffering
      adverse events during and after the procedure. Factors influencing perioperative
      events were age, duration of procedure and history of intraoperative events.

PMID- 8869650
TI  - [In memoriam Fidel Pages Mirave (1886-1923) on the 75th anniversary of the
      publication of "Anesthesia metamerica"].
AB  - Fidel Pages was born in Huesca on the 26th of January 1886. He completed his
      secondary studies in the same city, later receiving his degree in medicine and
      surgery from University of Zaragoza (1908) with high honors. The same year he
      joined the army medical corp, to be sent to serve in Melilla in 1909 with a rank
      of second medical officer. After being promoted in 1911 to first medical officer,
      he served in Tarragona, Toledo, Madrid (where received his doctoral degree),
      Ciudad Real, and once again in Madrid. In 1913 Pages married and was destined to
      Mahon, only to return to work at the War Ministry in Madrid in 1915, after a
      brief sojourn in Alicante. The same year he placed first in competition for a
      staff position at Madrid's Hospital Provincial. In 1917, during World War I, he
      inspected POW camps in Austria and Hungary, while also serving in the military
      hospital in Vienna. In 1919 he became the founding editor of Revista Espanola de
      Cirugia, which published "Anestesia metamerica" in 1921, simultaneous to its
      publication in Revista de Sanidad Militar. In 1920 on he was assigned to Madrid's
      Hospital Militar de Urgencia, but was also briefly sent to Melilla in 1921 as a
      consequence of the military "Disaster at Annual". In 1922 he was promoted to the
      rank of Medical Commandant. On the 21st of September 1923, Pages died in a
      traffic accident while returning to Madrid from San Sebastian. His work was soon
      forgotten, as can be seen from the credit long given to the Italian surgeon
      Dogliotti for the discovery of epidural anesthesia. Only with passing time, and
      through the effort of Argentinian and Spanish physicians, has the world come to
      recognize Pages as the original author of this technique.

PMID- 8869651
TI  - [Anesthesia for thoracoscopy].
AB  - The thoracoscopy is used both for diagnosis and treatment of pleural and lung
      diseases. We describe our experience in managing anesthesia for such procedures,
      the number of which is increasing thanks to technical advances. We review 82
      thoracoscopic procedures, 48 of which were video assisted. Sixty-two were
      performed under balanced general anesthesia (GA) with isoflurane, fentanyl and
      atracurium. Local anesthesia (LA) with fractionated doses of propofol and
      fentanyl was used in 20 cases. The mean age of patients receiving LA (63 +/- 17
      years) was significantly greater (p < 0.05) than those receiving GA (49 +/- 13
      years). ASA IV patients were given LA and sedation. Selective bronchial
      intubation was performed in 46 cases. Complications during surgery were severe
      hypoxemia (SpO2 < 85%) requiring suspension of selective lung ventilation in 8
      cases, moderate hypoxemia (spO2 < 90% and > 85%) in 1 case, coughing in 3 cases
      and agitation in 1 case. Video-thoracoscopy is a safe technique that is less
      invasive than conventional thoracotomy. The number of applications is increasing,
      although its future place in thoracic surgery must still be determined.

PMID- 8869652
TI  - [Utilization of inhaled nitric oxide in a case of respiratory insufficiency
      following lung transplantation].
AB  - Pulmonary hypertension and transient graft dysfunction may complicate the
      immediate postoperative course of patients undergoing lung transplantation. We
      report the effect of inhaled nitric oxide (NO) in a patient with pulmonary edema
      and severe hypoxemia in the period following bilateral lung transplantation. NO
      was delivered through the inspiratory line and its mean concentration was
      monitored in the trachea. PaO2/FiO2 improved from 65 to 105 with an NO
      concentration of 1 ppm, but no further improvement was obtained by increasing the
      dose to 5 ppm. Pulmonary vascular resistance (PVR) decreased from a baseline
      value of 251 dynes-sec/cm5 to a low of 213 dynes-sec/cm5 with NO administration.
      A slight increase in PVR seems to have been the main factor limiting the
      therapeutic efficacy of inhaled NO in this case.

PMID- 8869653
TI  - [Effect of acute intestinal obstruction on infrared systems for measuring
      anesthetic gases].

PMID- 8869654
TI  - [Thirst is the most common minor complication in the immediate postoperative
      period].

PMID- 8869655
TI  - [Transient global amnesia during subarachnoid anesthesia].

PMID- 8869656
TI  - [Epidural anesthesia combined with general anesthesia in ischemic
      cardiomyopathy].

PMID- 8869657
TI  - [Pneumomediastinum and subcutaneous emphysema as a complication of laparoscopic
      hiatal hernia surgery].

PMID- 8869658
TI  - [Intravenous regional anesthesia using low doses of lidocaine for hand surgery].

PMID- 8869659
TI  - [Safety of sevoflurane in humans].

PMID- 8869660
TI  - Quantities and units for biological reference materials used with in vitro
      diagnostic measuring systems for antibodies.
AB  - The WHO International Reference Materials (IRM), whether International Biological
      Standards (IS) (formerly International Reference Preparations (IRP)) or
      International Biological Reference Reagents (IRR), have served a good purpose in
      standardizing bioprocedures by defining international units of bioactivity or
      potency where dimensions seem difficult to establish. Especially for in vitro
      diagnostic procedures, the trend is towards measuring biochemically informative
      molecular-based quantities (involving the unit mole) when some chemical entity of
      a component can be defined. The use of a standard, with a value assigned by any
      procedure, as a calibrant in other procedures does not assure traceability and
      valid diagnostic results if the component (analyte) is microheterogeneous to a
      varying degree or there are varying matrix effects. Only experiment can
      demonstrate commutability of the material.

PMID- 8869661
TI  - The acute effect of smoking on systemic haemodynamics, kidney and endothelial
      functions in insulin-dependent diabetic patients with microalbuminuria.
AB  - The acute effect of smoking upon arterial blood pressure, urinary albumin
      excretion rate, glomerular filtration rate and transcapillary escape rate of
      albumin were investigated in nine normotensive insulin-dependent diabetic
      patients with microalbuminuria, who had been smoking for 19 (range 4-30) years.
      In a prospective, open randomized cross-over design, patients were investigated
      with and without smoking three cigarettes per hour during a 5.5-h period. A rise
      in systolic blood pressure and heart rate (Takeda TM2420, median (range)) was
      observed during the smoking day (10(-11 to 14) mmHg and 8 (-1 to 19) beats min
      1), compared to the non-smoking day (1 mmHg (-7 to 13) (p = 0.05) and 0 beats min
      1 (-2 to 4) (p < 0.01)). Urinary albumin excretion rate (ELISA), glomerular
      filtration rate (plasma clearance of 51Cr-EDTA) and transcapillary escape rate of
      albumin (125I-albumin) remained the same with or without smoking. Our study
      suggests that heavy smoking induces an abrupt rise in systolic blood pressure and
      heart rate, while vascular leakage of albumin and glomerular filtration rate
      remain unaltered in normotensive insulin-dependent diabetic patients with
      microalbuminuria who had been smoking for several years.

PMID- 8869662
TI  - The effects of palmitate on human erythrocyte membrane potential and osmotic
      stability.
AB  - To evaluate the mechanism(s) of erythrocyte stabilization in hypotonic medium by
      free fatty acids, we have studied the effect of palmitic acid and its derivatives
      on human erythrocyte membrane electrochemical properties, osmotic stability and
      fluidity. Palmitic acid increased the membrane potential to the highest extent as
      compared with its derivatives. The membrane potential was equal to -11.0 +/- 1.7
      mV in the absence and -23.3 +/- 3.2 mV in the presence of 400 mumol 1(-1) of
      palmitic acid, -15.3 +/- 2.2 mV in the presence of 400 mumol 1(-1) of methyl
      ester of palmitic acid and -14.2 +/- 1.8 mV in the presence of 400 mumol 1(-1) of
      lauric aldehyde. We propose that free fatty acids, containing the charged
      carboxylic end group, in contrast to the corresponding esters or aldehydes, can
      act as ionophores. At the same time, the osmotic stabilization of erythrocytes by
      palmitic acid and its derivatives was higher in sodium-containing as compared
      with potassium-containing media and did not correlate with the effect of these
      compounds on the membrane potential. We suggest that protective potassium leakage
      does not play a main role in erythrocyte osmotic stabilization by free fatty
      acids. Possibly this stabilization is due to the structural rearrangement of the
      whole membrane.

PMID- 8869663
TI  - Renal handling of radiolabelled human cystatin C in the rat.
AB  - Serum cystatin C concentration correlates negatively with glomerular filtration
      rate as well as or better than that of serum creatinine, suggesting a constant
      formation, and elimination from extracellular fluid mainly by glomerular
      filtration. It is not known, however, how well the renal plasma clearance of this
      13-kDa basic polypeptide matches the glomerular filtration rate. This was
      investigated in rats during control conditions and after reduced renal perfusion
      pressure. 125I-cystatin C and an indicator for glomerular filtration (51Cr-EDTA
      or 131I-aprotinin) were injected intravenously. The renal accumulation and
      urinary excretion of the tracers were recorded in periods of 2.5 to 20.0 min. The
      renal plasma clearance of 125I-cystatin C (Ccy) based on the renal content of
      125I correlated well with the glomerular filtration rate (CCr-EDTA) in periods up
      to 6 min; i.e. Ccy = 0.94 x CCr-EDTA, r = 0.99. Less than 0.5% of the filtered
      amount appeared in the urine. During more prolonged periods, Ccy increasingly
      underestimated glomerular filtration rate, reaching about 0.4 x CCr-EDTA in a 20
      min period. Free 125I relative to total plasma 125I activity increased from about
      2% at 5 min to about 70% at 20 min. In nephrectomized rats, free 125I accumulated
      in plasma at a slower rate, accounting for about 15% of the total activity 20 min
      after injection of 125I-cystatin C. We conclude that cystatin C is (a) mainly
      removed from the extracellular fluid by the kidneys, (b) practically freely
      filtered in the glomeruli, and (c) completely absorbed and rapidly broken down by
      the proximal tubular cells.

PMID- 8869664
TI  - Measurement of joint aspirate dilution by a spectrophotometer capillary tube
      system.
AB  - The amount of synovial fluid in small joints which is available for analysis of
      endogenous compounds is usually very limited and saline washings are therefore
      commonly required. However, since the washing fluid is not fully recovered and,
      furthermore, dilutes the synovial fluid in the joint aspirate, the true synovial
      fluid concentration of a particular substance is unknown. In the present study we
      validate the use of vitamin B12 (hydroxocobalamin, 1 mg ml-1) as an internal
      standard to determine this dilution, since its strong red colour lends itself to
      spectroscopic measurement by a capillary tube system requiring only 3 microliter
      per sample. The absorbance of different dilutions of the stock solutions (25, 33
      and 50% vitamin B12 in saline) by saline, plasma and hyaluronan was measured in
      order to establish the optimal wavelength, the lower limit of detection and the
      interference by plasma or hyaluronan in the absorbance. Furthermore, the
      interaction of vitamin B12 in the analyses of interleukin-1 beta, serotonin and
      glucose was investigated. The optimal wavelength was found to be 350 nm and the
      limit of detection 0.5-0.9% dilution of the vitamin B12 solution. Hyaluronan or
      plasma did not influence the absorbance measurements and the minute interaction
      of vitamin B12 in the photometric measurements could be compensated for.

PMID- 8869665
TI  - Folate and homocysteine status and haemolysis in patients treated with
      sulphasalazine for arthritis.
AB  - In an attempt to estimate the frequency of folate deficiency and haemolysis in a
      group of 25 outpatients with arthritis treated with sulphasalazine (SASP),
      haematological measurements, including plasma total homocysteine (tHcy) which is
      a sensitive marker of folate deficiency, serum folate (S-folate), erythrocyte
      (RBC) folate, S-cobalamin and routine indices of haemolysis were performed. No
      patient had been taking folate-containing vitamins for at least 8 weeks prior to
      the study. Compared to a group of 72 healthy hospital staff, the median plasma
      tHcy was significantly higher in the patient group (8.8 mumol 1(-1) vs. 6.8 mumol
      1(-1); p = 0.003). Five patients (20%) had plasma tHcy levels that exceeded the
      upper normal limit of plasma tHcy (median+2 SD of the reference group). Median S
      folate was significantly lower in the patient group (6.0 nmol 1(-1) vs. 8.5 nmol
      1(-1); p < 0.001), and 11 (44%) patients had depressed S-folate. Only three (12%)
      patients had RBC folate values below the reference interval. There was no
      difference in the levels of RBC folate between the two groups. A comparison of S
      cobalamin levels in the two groups disclosed a significantly lower level in the
      patient group. However, no patient had cobalamin deficiency as assessed by S
      cobalamin and S-methylmalonate measurements. Thus, it is unlikely that any
      patient had increased plasma tHcy due to cobalamin deficiency. Of 24 patients
      having a HbA1c measurement performed, 12 (50%) had decreased levels indicating
      chronic haemolysis. Only seven (28%) patients had reticulocytosis. HbA1c was
      positively correlated to haptoglobin levels (r = 0.77; p < 0.001) and negatively
      correlated to the percentage of reticulocytes (r = -0.50; p = 0.02). The
      percentage of reticulocytes was negatively correlated to haptoglobin levels (r = 
      0.42; p = 0.04). The chronic haemolysis of the patients' blood due to SASP might
      explain the similar RBC folate values in the two groups because of a relatively
      higher folate content of young erythrocytes. In conclusion, our results support
      previous findings of folate deficiency and haemolysis occurring in a considerable
      fraction of patients receiving treatment with SASP. Measurements of plasma tHcy
      suggest that a substantial number of patients may have folate deficiency at the
      tissue level.

PMID- 8869666
TI  - Perfusing isolated rat hearts with hydrogen peroxide: an experimental model of
      cardiac dysfunction caused by reactive oxygen species.
AB  - A model of cardiac dysfunction induced by reactive oxygen species (ROS) was
      established by adding hydrogen peroxide (H2O2) to the perfusate of isolated,
      Langendorff-perfused rat hearts, and the mechanism of functional injury was
      investigated. The following groups were included: 1 (n = 7), control perfusion; 2
      (n = 11), perfusion with H2O2 (180 mumol 1(-1) for 10 min followed by recovery
      for 50 min; 3 (n = 4), control perfusion with N-acetylcysteine (NAC, 100 mumol 1(
      1); 4 (n = 7), perfusion with H2O2 and NAC; 5 (n = 4), control perfusion with
      thiourea (15 mmol 1(-1), 6 (n = 7), H2O2 and thiourea together; 7 (n = 4),
      control perfusion with catalase (150 U ml-1); 8 (n = 7), catalase and H2O2, 9 (n
      = 4), control perfusion with deferoxamine (5 mmol 1(-1); and 10 (n = 7),
      deferoxamine and H2O2. coronary flow (CF), left ventricular developed pressure
      (LVDP), left ventricular end-diastolic pressure (LVEDP), and heart rate (HR) were
      measured. All values are mean +/- SEM. When given alone, catalase, thiourea, NAC
      and deferoxamine did not influence left ventricular pressures, but NAC, catalase
      and thiourea increased CF. H2O2 increased CF (maximum 146 +/- 6% of baseline
      value after 5 min, p < 0.001 compared to group 1), decreased LVDP (minimum 14 +/-
      5% of baseline value after 10 min, p < 0.0004), and increased LVEDP (from 0 mmHg
      to a maximum of 54 +/- 7 mmHg after 5 min recovery, p < 0.0003). All these
      changes gradually reversed during recovery. Catalase and thiourea both inhibited
      the H2O2-induced effects, but catalase inhibition was more complete. Neither NAC
      nor deferoxamine had any effect on H2O2-induced cardiac dysfunction. In
      conclusion, H2O2 perfusion is a convenient and reversible model of ROS-induced
      functional injury to isolated rat hearts. H2O2, rather than the hydroxyl radical,
      seems to be the main injurious ROS in this model.

PMID- 8869667
TI  - Effect of alcohol abuse and glutathione administration on the circulating levels
      of glutathione and on antipyrine metabolism in patients with alcoholic liver
      cirrhosis.
AB  - Glutathione (GSH) is a principal cellular scavenger of free radicals. Chronic
      alcohol abuse, as well as liver disease, induces a decrease of hepatic GSH. We
      evaluated the effect of GSH administration (2.4 g day-1 in saline i.v. for 15
      days) on the concentration of GSH in plasma and erythrocytes and on liver
      function tests, including galactose and antipyrine tests. We studied 40 alcoholic
      cirrhotic patients: 22 treated with GSH (10 persistent alcohol abusers and 12
      weaning from alcohol during the study) and 18 treated with saline only (8
      persistent alcohol abusers and 10 abstainers). Treatment with GSH improved the
      concentration of GSH in plasma and erythrocytes only in abstainers from alcohol;
      it did not affect liver function tests or galactose clearance. Persistent alcohol
      consumption significantly prolonged antipyrine metabolism; GSH administration
      counteracted this effect.

PMID- 8869668
TI  - Effect of prednisolone on amino acid-induced changes in renal haemodynamics and
      tubular function.
AB  - The effect of oral prednisolone treatment on renal haemodynamics, tubular
      function and various hormones during amino acid infusion was studied in 14 normal
      men. A balanced amino acid solution was infused for 120 min, before and after 4
      days of prednisolone treatment (40 mg day-1). During amino acid infusion before
      prednisolone glomerular filtration rate, renal plasma flow, urinary sodium
      excretion, fractional excretion of sodium, lithium clearance, fractional
      excretion of lithium, serum insulin (s-insulin), plasma glucagon (p-glucagon) and
      s-growth hormone increased, whereas p-atrial natriuretic peptide, p-aldosterone,
      p-vasopressin and s-insulin-like growth factor 1 were unchanged, and potassium
      excretion and fractional excretion of potassium fell. After prednisolone
      treatment the most important differences during amino acid infusion were a
      significantly lower fractional excretion of sodium after 120 min (before
      prednisolone 26%; after prednisolone-7%; p < 0.05), a more pronounced increase in
      s-insulin after 120 min (before 118%; after 200%; p < 0.05) and a lower s
      potassium. In conclusion, amino acid infusion increased fractional sodium
      excretion in healthy men, and this increase was reduced by prednisolone due to
      increased reabsorption in the distal tubules. It is suggested that the more
      pronounced the increases in plasma insulin and the decrease in serum potassium
      are mediators of the increased distal tubular sodium reabsorption during amino
      acid infusion during prednisolone treatment.

PMID- 8869669
TI  - Release of cytokines and proteases from human peripheral blood mononuclear and
      polymorphonuclear cells following phagocytosis and LPS stimulation.
AB  - Release and cellular contents of pro- and anti-inflammatory cytokines,
      neutrophilic elastase and secretory leukocyte proteinase inhibitor (SLPI) were
      measured with enzyme-linked immunosorbent assay in peripheral blood mono- and
      polymorphonuclear cells stimulated with preopsonized yeast cells or
      lipopolysaccharide. Tumour necrosis factor alpha (TNF alpha) was also measured
      with a bioassay. TNF alpha production and soluble TNF alpha receptor I (sTNF RI)
      were demonstrated in the environment of both cell populations. The bioassay
      indicated levels of TNF alpha far below those detected by ELISA. The overall
      secretion of cytokines and their inhibitors was found to favour an anti
      inflammatory balance in the environment of the stimulated cells. The interleukin
      1 receptor antagonist (IL1-ra), compared with interleukin-1 beta (IL-1 beta),
      dominated the secretions from both cell types with a 100- to 1000-fold excess
      respectively. Most of the translated IL-1 beta was not secreted but found
      associated with the cellular compartments. In contrast to lipopolysaccharide
      (LPS) stimulation, preopsonized yeast cells stimulated a massive release of
      elastase from neutrophil cells.

PMID- 8869670
TI  - Ambulatory blood pressure reproducibility and application of the method in a
      healthy Finnish cohort.
AB  - The aim of the present study has been to study the reproducibility, validity and
      normal values of ambulatory blood pressure measurement in a healthy Finnish
      cohort. The reproducibility of ambulatory blood pressure monitoring was examined
      in healthy volunteers and normal values were determined in a Finnish cohort of
      males and women of different ages. In the reproducibility study the recording was
      repeated at 2-week intervals. In the validity study simultaneous measurements
      were done manually with a mercury sphygmomanometer and compared with the
      measurement by the ambulatory blood pressure recording unit, both connected with
      the cuff by a T-tube; this study included 100 consecutive measurements in a
      patient group. A relatively small cohort was taken from the normal value study
      group. In addition to ambulatory blood pressure their left ventricle mass was
      also determined by echocardiography. The correlation between manual blood
      pressure measurement and simultaneous measurement by the ambulatory blood
      pressure unit was 0.98. In the reproducibility study the correlations between the
      two 24-h measurements 2 weeks apart were also good. Depending on the parameter
      (daytime, nighttime or 24-h blood pressure mean, systolic or diastolic values)
      the correlation coefficient varied between 0.81 and 0.91. Thus both systolic and
      diastolic blood pressures, whether expressed as 24-h averages and daytime or
      nighttime averages, correlated well between these two recording sessions. The
      data obtained in the present Finnish cohort were well within the published
      reference value limits, showing only fairly modest age-dependence appearing at
      quite an old age. There was no significant correlation between the left ventricle
      mass and ambulatory blood pressure values in a population having normal blood
      pressure. The results suggest good intra-individual correlation and
      reproducibility in ambulatory blood pressure monitoring, suggesting this method
      to be useful in the monitoring of individual blood pressure levels. The validity
      of the method is good and the published reference values can be applied with
      reasonable reliability in different populations. In an adult population with
      normal blood pressure, no correlation between left ventricle mass and blood
      pressure values can be found, suggesting this correlation may first appear in
      cohorts including persons with elevated blood pressure values.

PMID- 8869671
TI  - Comparison of neuromuscular block of atracurium and rocuronium in adults.
AB  - We studied the time-course of action of atracurium 0.5 mg kg-1 and rocuronium 0.6
      mg kg-1 in 24 healthy adult patients. Anesthesia was induced with thiopentone and
      sufentanil, and maintained with 50% nitrous oxide and 1% enflurane in oxygen.
      Neuromuscular transmission was monitored by stimulating the ulnar nerve at the
      wrist and measuring the acceleration of the thumb using the TOF-Guard
      accelerograph monitor. Supramaximal stimuli of 0.2 ms duration were applied in a
      single twitch stimulation mode at 1 Hz frequency until completion of block, and
      in train-of four (TOF) sequence at 2 Hz every 15 sec thereafter. Onset time was
      longer with atracurium (mean +/- SD:90 +/- 18 sec) than with rocuronium (49 +/- 6
      sec). Clinical duration of action (Tl25) was longer with atracurium (52.3 +/- 7.2
      min) than with rocuronium (40.0 +/- 6.4 min). Recovery index (Tl25-Tl75) and time
      for TOF ratio to recover to 0.75 were 17.8 +/- 4.2 and 73.9 +/- 8.8 min with
      atracurium, and 13.8 +/- 4.1 and 70.4 +/- 14.1 min with rocuronium. The
      differences between both groups were statistically significant except the
      difference in the time for TOF to return to 0.75.

PMID- 8869672
TI  - Effects of pipecuronium and pancuronium on cerebrospinal fluid pressure in
      neurosurgical patients.
AB  - Arterial hypertension and/or tachycardia may alter intracranial pressure in
      neurosurgical patients. We compared the effects of pancuronium 0.1 mg/kg and
      pipecuronium 0.1 mg/kg given as i.v. bolus on cerebrospinal fluid (CSF) pressure
      in 2 groups of 10 patients each scheduled for intracranial surgery in the supine
      position. Before surgery, no patient presented clinical symptoms of elevated
      intracranial pressure (ICP). Anesthesia was induced and maintained with fentanyl
      and midazolam. Ventilation with 50% nitrous oxide in oxygen was adjusted to
      maintain arterial pCO2 at 30-35 mmHg. After induction of anesthesia, CSF pressure
      was registered via a lumbar subarachnoid catheter before and 3, 5, 10, and 30 min
      after pipecuronium or pancuronium administration. Hemodynamics were monitored
      using radial and pulmonary artery catheters. All variables underwent analyses of
      variance for repeated measures with p < 0.05 considered significant. Mean CSF
      pressure decreased insignificantly from 15 +/- 5 mmHg (before injection) to 14 +/
      4 mmHg in patients given pipecuronium and from 13 +/- 4 mmHg to 10 +/- 3 mmHg in
      the pancuronium group without significant differences between the study groups.
      Heart rate and arterial pressure increased significantly (p < 0.001) in patients
      given pancuronium but remained stable after pipecuronium. Onset and duration of
      neuromuscular blockade were comparable between groups. Based on our results,
      pipecuronium is a safe alternative to pancuronium during neurosurgical procedures
      in patients without abnormally high intracranial pressure.

PMID- 8869673
TI  - Carboxyhemoglobin concentrations during desflurane and isoflurane closed-circuit
      anesthesia.
AB  - Desflurane has been implicated in carbon monoxide (CO) intoxication during
      general anesthesia under certain circumstances. Carboxyhemoglobin (COHb)
      concentrations were determined in forty-one patients who were randomly allocated
      to receive closed-circuit anesthesia (CCA) with 1.3 MAC of desflurane (n = 21) or
      isoflurane (n = 20) in oxygen. Soda lime was used to bind the produced CO2 in
      previous anesthetic procedures with fresh gas flows of < 21/min. In the
      desflurane group, COHb concentrations (mean +/- SD) were 0.86 +/- 1.15% and 0.81
      +/- 1.11% before and after 1 h of anesthesia, respectively. In the isoflurane
      group, COHb concentrations were 1.15 +/- 1.47% and 1.19 +/- 1.39% before and
      after 1 h of anesthesia, respectively. COHb concentrations did not increase after
      2 h of CCA in seven patients. Our data suggest that closed-circuit anesthesia
      with desflurane or isoflurane does not produce clinically significant increases
      in COHb concentrations under conditions that allow the soda lime to remain
      sufficiently wet.

PMID- 8869674
TI  - Effects of three techniques of lung management on pulmonary function during
      cardiopulmonary bypass.
AB  - In this study, 30 patients undergoing elective myocardial revascularization were
      divided randomly in three groups (10 patients each) with different management of
      the lungs during CPB: Group 1, lungs deflated; Group 2, static inflation with
      PEEP = 5 cmH2O and FIO2 = 1.0; Group 3, static inflation with PEEP = 5 cmH2O and
      FIO2 = 0.21. Measurements (Qs/Qt, P(A-a)O2, PaO2, Cstat, Cdyn, PIP, AUTO-PEEP,
      Rrs,max, Rrs,min and DRrs) were performed after the induction of anesthesia (T0),
      20 minutes (T1) and 2 hours (T2) after the end of CPB. Respiratory mechanics data
      were obtained only at T0 and T2 because the sternal retraction. The Group 1
      presented a statistically significant increase in Qs/Qt, P(A-a)O2 and Peak
      Inspiratory Pressure (PIP); in this group we noticed also a decrease in PaO2
      values, static compliance (Cstat) and dynamic compliance (Cdyn) values comparing
      basal versus T1 and T2 values. The Group 2 showed a statistically significant
      increase in Qs/Qt and P(A-a)O2 values; also in this group we observed a
      statistically significant decrease in PaO2 and Cdyn values comparing basal versus
      T1 and T2 values. The Group 3 presented a statistically significant decrease in
      PaO2 values (basal versus T1 and T2); this group also presented an increase in
      Qs/Qt values, in the immediate postbypass period (T1), and P(A-a)O2 values
      significantly increase comparing basal versus T1 and T2 values. In all the three
      groups the respiratory system resistance and AUTO-PEEP values were unchanged
      after the end of CPB. The comparison between the groups showed a significant
      minor impairment of gas exchange (PaO2 and P(A-a)O2), Qs/Qt and Cstat in the
      third group of patients. These results show that lungs inflation with air during
      CPB, effectively preserve respiratory system mechanics: this might be due to a
      preservation of bronchial perfusion simply due to the mechanic expansion of the
      lung otherwise compromized when the lungs are completely collapsed. However it is
      necessary to emphasize that CPB has negative effects on gas-exchange whatever
      technique of lung management is used.

PMID- 8869675
TI  - A comparison of the laryngeal mask and tracheal tube for controlled ventilation.
AB  - The use of laryngeal mask airway (LMA), size 3 or 4, and endotracheal tube (ETT)
      8.0 mm was studied comparatively to determine the adequacy of respiratory
      function during positive pressure ventilation (PPV) by applying a series of given
      peak inspiratory pressures (PIPs) of 10.0, 12.5, 15.0, 17.5, 20.0 and 30.0 cm
      H2O. Eleven anesthetised patients underwent a double comparative trial. First
      they were ventilated via the LMA and afterwards via the ETT. Tidal volume (VT),
      dynamic compliance, end-tidal carbon dioxide and peripheral oxygen saturation
      were recorded in a supine position, before skin incision. Higher values of VT
      (1.7 mk.kg-1) were expired via the LMA compared with ETT when a given PIP of less
      than 20 cmH2O was applied. LMA as opposed to ETT secured normocapnia during PPV
      with low PIPs.

PMID- 8869676
TI  - Esmolol for hypotensive anesthesia in middle ear surgery.
AB  - This study was performed to investigate the efficacy of esmolol, an agent used in
      hypotensive anesthesia for middle ear surgery. We compared 20 ASA I-II patients
      to 20 controls in whom we administered routine anesthesia. All patients were
      premedicated with intramuscular 0.05 mg/kg atropine, 1 mg/kg pethidine and 25 mg
      promethazine. Anesthesia was induced with 0.004 mg/kg fentanyl and 5 mg/kg
      thiopental sodium. Succinylcholine 1.5 mg/kg was administered to facilitate
      intubation. Isoflurane, nitrous oxide, oxygen, 0.08 mg/kg vecuronium bromide and
      controlled ventilation were used for anesthetic maintenance. Before the
      controlled hypotensive period, nitrous oxide was discontinued and an esmolol
      infusion started. We registered hemodynamic values (via noninvasive and invasive
      radial artery cannulation), central venous pressure, electrocardiography, body
      temperature, end-tidal carbon dioxide levels, periferal oxygen saturation, and
      arterial blood gas analysis. Mean infusion rate of esmolol was 330 +/- 10
      micrograms/kg/min. We found significant decreases in systolic blood pressure
      (28.7%), mean blood pressure (26.5%) and diastolic blood pressure (33.4%). The
      operative field was virtually bloodless. Hemodynamic values recovered to normal
      or to within -12.45% of normal at the end of intravenous esmolol infusion. During
      the postoperative period, no side effects were observed. In conclusion, esmolol
      is an appropriate hypotensive agent for patients undergoing middle ear surgery
      under hypotensive anesthesia because it yields no side effects, it is easy to
      control administration and it provides the desired degree of hypotension without
      complications.

PMID- 8869678
TI  - Impaired expression of stem cell factor in dermatofibroma fibroblasts.
AB  - The number of mast cells is increased in dermatofibroma lesions and plays a role
      in the induction of fibrosis or its proliferation. We have investigated stem cell
      factor expression in solitary and multiple dermatofibromas by immunohistochemical
      straining. We also analyzed messenger RNA (mRNA) expression of stem cell factor
      in dermatofibroma tissues and cultured fibroblasts derived from dermatofibromas,
      using reverse transcriptase polymerase chain reaction. We found immunoreactive
      stem cell factor in keratinocytes, dermal fibroblasts, melanocytes and hair
      follicles. Unexpectedly, a reduced expression of immunoreactive stem cell factor
      in dermatofibroma fibroblasts was observed in solitary and multiple type.
      However, mRNA expression of stem cell factor was detected both in the
      dermatofibroma tissue and cultured dermatofibroma-derived fibroblasts. We
      speculate that the altered expression of stem cell factor of tumor cells in
      dermatofibroma lesions can be associated with the tumor cell proliferation and
      induction of dermatofibroma.

PMID- 8869679
TI  - Ethanol enhances the mitogen-driven lymphocyte proliferation in patients with
      psoriasis.
AB  - Ethanol has been reported to exacerbate psoriasis. Since immunological mechanisms
      are considered to be important for the pathogenesis of psoriasis, we compared the
      effects of ethanol on lymphocyte proliferation in 15 healthy control individuals
      and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin
      in (PHA)-induced uptake of 3H-TdR to measure lymphocyte proliferation. Ethanol
      was added to cultures at concentrations ranging from 0.5 to 0.0005% (vol./vol.).
      We found that both spontaneous and PHA-driven lymphocyte proliferations were
      significantly lower in patients with psoriasis (P < 0.002). Spontaneous
      blastogenesis in both controls and patients remained stable under ethanol. In
      controls, ethanol suppressed the PHA-driven lymphocyte proliferation in a dose
      dependent fashion. By contrast, in patients with psoriasis ethanol significantly
      increased lymphocyte proliferation by 2-3 times (p < 0.002). Our data indicate
      that in psoriasis the lower lymphocyte transformation is abnormally enhanced by
      minimal doses of ethanol.

PMID- 8869680
TI  - Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as
      topical photoprotectants.
AB  - Considerable interest has been recently generated concerning the use of natural
      compounds, anti-oxidants in particular, in photoprotection. Two of the best known
      anti-oxidants are vitamins C and E, both of which have been shown to be somewhat
      effective in different models of photodamage. Very little has been reported,
      however, on the effectiveness of a combination of the two (known to be
      biologically the more relevant situation); nor have there been detailed studies
      on the ability of these antioxidants to augment commercial sunscreen protection
      against UV damage. We report that (in swine skin) vitamin C is capable of
      additive protection against acute UVB damage (sunburn cell formation) when
      combined with a UVB sunscreen. A combination of both vitamins E and C provided
      very good protection from a UVB insult, the bulk of the protection attributable
      to vitamin E. However, vitamin C is significantly better than vitamin E at
      protecting against a UVA-mediated phototoxic insult in this animal model, while
      the combination is only slightly more effective than vitamin C alone. When
      vitamin C or a combination of vitamin C and E is formulated with a commercial UVA
      sunscreen (oxybenzone), an apparently greater than additive protection is noted
      against the phototoxic damage. These results confirm the utility of anti-oxidants
      as photoprotectants but suggest the importance of combining the compounds with
      known sunscreens to maximize photoprotection.

PMID- 8869681
TI  - The vitronectin receptor alpha-V beta-3, contrary to ICAM-1, is not modulated by
      interferon-gamma and tumour necrosis factor-alpha on melanoma cell lines.
AB  - A correlation was recently shown between expression of the vitronectin receptor
      (VnR) and the tumorigenic capacity of cultured human melanoma cell lines. On the
      other hand, modulation of VnR expression by interferon-gamma (IFN-gamma) and
      tumour necrosis factor-alpha (TNF-alpha) was observed on different non-melanoma
      cell lines. We tested IFN-gamma, TNF-alpha and interleukin-2 (IL-2), which are
      presumably released by infiltrating leukocytes in the melanoma lesional
      environment, on three melanoma cell lines. The VnR expression was assessed using
      FACS analysis and radioimmunolabelling. The VnR did not show any modulation after
      treatment with any of the cytokines tested. By contrast, the expression of the
      intercellular adhesion molecule-1 (ICAM-1), tested as control, on five melanoma
      cell lines, was greatly enhanced by IFN-gamma and TNF-alpha. Thus, some host
      cytokines may preferentially induce melanoma cells to express ICAM-1 (which can
      increase host cytotoxic response against melanoma), other than the VnR (which
      instead might contribute to melanoma metastasis).

PMID- 8869682
TI  - Temperature dependency of skin susceptibility to water and detergents.
AB  - Exposure to water and detergents is an important factor for development of
      irritant contact dermatitis. The aim of the present study was to investigate the
      effect of temperature on the damaging effects of water and detergents on the
      skin. Twenty healthy volunteers participated in the study. Ten participants had
      right and left forearms immersed into a detergent (soap) solution for 2 days
      twice daily for 10 min. Another 10 participants had both forearms immersed into
      sterile water. Right and left forearms were randomized to immersion into 20
      degrees C and 40 degrees C solutions, respectively. Reactions were evaluated
      clinically, and by measurement of transepidermal water loss, electrical
      capacitance and erythema. Immersions into 40 degrees C sodium lauryl sulphate
      solution caused significantly increased transepidermal water loss as compared to
      immersion into 20 degrees C sodium lauryl sulphate solution. Electrical
      capacitance and erythema were not significantly influenced by temperature.
      Immersion into water caused no significant changes in any observed parameter.
      Water temperature influences the irritant capacity of a detergent. Change of
      temperature may be a simple but important means for prevention of irritant
      contact dermatitis.

PMID- 8869683
TI  - Cyclophosphamide and interleukin-12 synergistically upregulate the acquisition of
      allergic contact dermatitis in the mouse.
AB  - Cyclophosphamide given before allergen and recombinant interleukin-12
      administered at the time of allergic sensitization substantially increase the
      acquisition of allergic contact dermatitis in the mouse. Since their
      immunoadjuvant mechanisms appeared different, it seemed probable that combining
      cyclophosphamide pretreatment with interleukin 12 administration would result in
      a more intense allergic contact dermatitis than when either agent was used alone.
      This was tested in different groups of mice sensitized to dinitrofluorobenzene or
      to oxazolone. Consistently, immunopotentiation of allergic contact dermatitis was
      significantly greater with the two immunoadjuvants than with either alone. This
      immunoadjuvant combination is likely to find use in immunization protocols
      designed to induce a Th-1 helper cell response.

PMID- 8869684
TI  - Effect of oral terbinafine treatment on cyclosporin pharmacokinetics in organ
      transplant recipients with dermatophyte nail infection.
AB  - Eleven patients with either kidney, heart or lung transplants, immunosuppressed
      with cyclosporin A, and with culture-proven dermatophyte toe nail infection, were
      given 250 mg terbinafine orally daily for 12 weeks. No changes in cyclosporin A
      dosage were made. A statistically significant decrease in mean specific
      cyclosporin A blood trough levels was found at 4, 8 and 12 weeks. No other
      statistically significant changes in the pharmacokinetic profile of cyclosporin A
      were seen. Terbinafine possibly induces a cyclosporin A metabolic degradation,
      which, however, is of little clinical significance. Terbinafine treatment is a
      safe therapeutical option in cyclosporin A-treated patients with dermatophyte
      nail infection. Cyclosporin A levels should be controlled during treatment.

PMID- 8869685
TI  - Expression of gastrin-releasing peptide receptor in human skin.
AB  - Bombesin-related peptides are expressed in the skin of batrachians and mammals.
      As gastrin-releasing peptide belongs to this family, we searched for the presence
      and distribution of gastrin-releasing peptide receptors (GRPr) in the skin of
      healthy human adults by immunohistochemistry, flow cytometry and electron
      microscopy. The results indicated that GRPr are expressed on nerves and vessels
      in the dermis, on eccrine sweat glands, sebaceous glands and erector pili muscle.
      Within epidermis, staining was localized only on basal and suprabasal layer
      cells, or in the whole epidermis, according to the samples studied.
      Interestingly, suprabasal epidermal dendritic cells occasionally showed a strong
      labelling. Some of these epidermal dendritic cells were identified as Langerhans'
      cells by immunoelectron microscopy studies. Flow cytometry analysis of crude
      epidermal cell suspensions resulted in the expression of GRPr on about 43% of the
      cells. Therefore, we investigated whether human GRPr could modulate Langerhans'
      cells antigen-presenting functions. For this purpose, we added increasing
      concentrations of GRP (10(-12) to 10(-5) M) to mixed epidermal cell lymphocyte
      reactions. Allogeneic T-cell proliferation was not significantly modified when
      added to GRP-pretreated epidermal cells. In conclusion, we demonstrated the
      presence of GRPr in human skin, suggesting that GRP may modulate epidermal cell
      functions but does not modify antigenic presentation.

PMID- 8869686
TI  - Regulation of collagen expression by interleukin-1 beta is dependent on donor
      age.
AB  - Cultured skin fibroblasts derived from old (> 60 years) donors differ in various
      morphological and functional aspects from cells obtained from young (< 20 years)
      donors. We were interested in whether fibroblasts obtained from old and young
      donors differ in their cellular response to interleukin-1 beta, a cytokine which
      has been shown to affect the synthesis of extracellular matrix proteins in human
      dermal fibroblasts. Therefore the expression of interstitial collagen (type I),
      minor collagen (type VI) and interstitial collagenase genes was investigated,
      using fibroblasts derived from either old or young donors. Fibroblasts were
      incubated in the absence or presence of interleukin-1 beta (5 units/ml, 50
      units/ml, 500 units/ml) for 48 h. Total RNA was isolated and mRNA levels were
      determined by Northern and dot blot analysis. Comparing the synthetic response of
      fibroblasts obtained from young and old donors, we observed a marked increase of
      the inhibition of type I and type VI collagen expression and the stimulation of
      interstitial collagenase in the aged fibroblasts. These results suggest that
      physiological ageing in human fibroblasts is associated with an altered
      responsiveness to interleukin-1 beta.

PMID- 8869687
TI  - Evaluation of port wine stains by laser Doppler perfusion imaging and reflectance
      photometry before and after pulsed dye laser treatment.
AB  - Treatment of choice for congenital capillary malformations of the port wine stain
      type is presently the pulsed dye laser. Although treatment results have usually
      been excellent or good, a few patients respond less well. Looking for a tool to
      predict and monitor the treatment we used laser Doppler perfusion imaging and
      reflectance photometry. Measurements with laser Doppler perfusion imaging were
      performed in 19 patients initially and after 1-3 treatments and with reflectance
      photometry initially and after 1-6 treatments. Before treatment, 15 of the
      patients had an increased bloodflow within the port wine stain in comparison with
      normal contralateral skin. After the laser treatments, 15 of 18 patients had
      decreased bloodflow within the lesion and all 18 had surrounding hyperemia.
      Reflectance photometry showed a successive increase in blanching and predicted
      within 6 weeks of the first treatment the eventual clinical result. The
      bloodflow, as measured with laser Doppler perfusion imaging, did not correlate
      well with the photometrically registered erythema. Reflectance photometry is a
      useful objective tool, which early in the treatment course indicates whether
      laser therapy will be successful. Laser Doppler perfusion imaging is less helpful
      in monitoring patients but may be of use in the study of port wine stain
      pathophysiology.

PMID- 8869688
TI  - Acute urticaria: clinical aspects and therapeutic responsiveness.
AB  - Although acute urticaria is common, its eliciting factors, clinical course and
      therapeutic responsiveness have not been intensively investigated. We have
      therefore prospectively studied all patients with acute urticaria attending the
      department of dermatology (n = 72) and a rural dermatology office (n = 37) during
      the course of 1 year. After a standardized history and physical examination,
      patients were randomized into treatment with either loratadine (10 mg/day for 3
      days) or prednisolene (50 mg/day for 3 days). All patients were followed up until
      complete remission. Most patients suffered from moderate (42%) to severe (40%)
      disease. Possible eliciting factors were identified in less than 50% of the
      cases. Associated upper respiratory tract infections were found most commonly
      (39.5%), followed by possibly eliciting drugs, mostly analgesics (9.2%) and
      suspected food intolerance (0.9%). The course of the disease was self-limited in
      all cases, the longest episode lasting for 3 weeks. Both treatment regimens were
      effective in controlling whealing, but in corticosteroid-treated patients,
      symptoms ceased earlier, with complete remission occurring within 3 days of
      treatment in 93.8%, compared to 65.9% of patients treated with loratadine (p <
      0.001). Acute urticaria is thus frequently idiopathic and only rarely associated
      with IgE-mediated events. It is, however, largely self-limited, with prompt
      response to symptomatic treatment.

PMID- 8869689
TI  - Autosomal recessive cutis laxa syndrome. A case report.
AB  - Congenital cutis laxa (CCL) is a rare, genetically heterogeneous connective
      tissue disorder, manifested by loose, hanging skin, giving the appearance of
      premature aging. We report a 6-year-old female child with autosomal recessive CCL
      type III, to assess possible correlations between clinical, ultrastructural,
      cellular and biochemical features. Morphological aberrations of the elastic and
      collagen tissue, increased collagen I mRNA expression associated with increased
      protein synthesis and increased collagenase gene expression of the cutis laxa
      fibroblasts could be established. Our results suggest that CCL is not only a
      disease of the elastic fibers of the connective tissue but also of the collagen
      fibers, with a central role of the fibroblast.

PMID- 8869690
TI  - Macular posterior pigmentary incontinence: its relation to macular amyloidosis
      and notalgia paresthetica.
AB  - Patients with clinical features of dorsal macular amyloidosis but without
      subepidermal amyloid deposits were followed for 2-11 years. The clinical
      appearance was fairly stable during this period of time, with little tendency of
      healing. Only 2 of the patients developed typical macular amyloidosis during the
      follow-up. It is concluded that a condition strongly resembling macular
      amyloidosis but without amyloid is an entity, and the designation "macular
      posterior pigmentary incontinence" is proposed. The relationship between macular
      posterior pigmentary incontinence and the two conditions macular amyloidosis and
      notalgia paresthetica is discussed.

PMID- 8869691
TI  - Increased collagen propeptides in the skin of a scleredema patient but no change
      in re-epithelialisation rate.
AB  - Scleredema is a rare disease, affecting the skin connective tissue with increased
      amounts of collagen and glycosaminoglycans. In the present study, the collagen
      synthesis and re-epithelialisation rate were measured from a 64-year-old male
      patient, who rapidly developed extensive tightening of the skin, without any
      underlying disease. The skin was thickened at several sites when measured with
      ultrasound, and the histology revealed accumulation of glycosaminoglycans and
      collagen bundles. The collagen synthesis rate was measured from suction blisters
      induced on two different sites of the skin before the treatment and three times
      later up to 6 months after the treatment with a systemic steroid was started. The
      aminoterminal propeptide of type I collagen (PINP) was increased manifold in the
      affected skin when compared with the controls, indicating active collagen
      deposition in vivo. Systemic steroid medication with high doses (over 20 mg/d)
      decreased both the type I and the type III collagen propeptide levels. The time
      schedule of the decreases in the propeptides in the thickened, affected skin and
      in the clinically normal-looking skin varied, and especially in the thickened
      skin in the abdomen the decrease in PINP was noted only after 3 months of
      prednisolone therapy. When the prednisolone dose was only 10 mg daily, the
      propeptides were again up-regulated, perhaps reflecting the natural course of the
      disease. The re-epithelialisation rates at two different sites of the patient
      were similar to those in the controls, suggesting that even massive fibrosis with
      active deposition of collagen does not alter the basal rate of re
      epithelialisation in the skin. In conclusion, collagen synthesis is markedly
      elevated in scleredema, leading to fibrosis of the skin. A recently developed
      method utilizing assays of collagen propeptides from suction blister fluid allows
      monitoring of the collagen synthesis and detection of changes in the collagen
      synthesis during the treatment of fibrotic disorders.

PMID- 8869692
TI  - Delayed-type hypersensitivity in palmoplantar pustulosis: effect of cyclosporin A
      treatment on skin testing with recall antigens.
AB  - Delayed-type hypersensitivity reactions to skin antigens are an indirect measure
      of cellular immune response. We studied in a double-blind manner whether
      clinically effective doses of cyclosporin A in palmoplantar pustulosis would
      diminish delayed-type hypersensitivity reactions in vivo. For testing delayed
      type hypersensitivity, we applied intradermally a standardized panel of seven
      recall antigens and a vehicle control in 30 patients with palmoplantar
      pustulosis, and 28 were tested both at baseline and after 4 weeks. For 4 weeks 14
      patients were treated with 2.5 mg/kg/day cyclosporin A and 14 patients with
      placebo. Cyclosporin A but not placebo caused a significant decrease in clinical
      disease parameters. In contrast, no significant differences in delayed-type
      hypersensitivity reactions between treatment groups were observed. The results do
      not support the view that the efficacy of low-dose cyclosporin A in
      dermatological disorders can be entirely explained by cyclosporin A's inhibitory
      actions on effector T-cells.

PMID- 8869693
TI  - Skin disease and age-related cataract.
AB  - Dermatological conditions and treatments were analysed in a study comparing
      cataract patients and stringently matched controls. One thousand patients were
      taken from the cataract waiting list of a specialist eye hospital. For each
      patient a matched control of the same gender, half-decade of age, and family
      doctor but without cataract was selected. Venepunctures and eye examinations were
      performed on both patients and controls; in addition, questionnaire information
      was obtained from each. Age-related cataract is significantly associated with
      dermatological abnormality and its treatment, the former association being more
      significant and more pronounced after 69 years of age. The association of
      hydrocortisone use after 69 years of age and cataract, however, remains
      significant even after adjustments for dermatological abnormality and steroid
      use, suggesting that even among steroid medications hydrocortisone is
      particularly strongly associated with cataract.

PMID- 8869694
TI  - Foil bath PUVA in the treatment of prurigo simplex subacuta.
AB  - Prurigo simplex subacuta is a chronic pruritic condition of unknown aetiology.
      The skin lesions respond to topical corticosteroids, UV-A and UV-B therapy only
      to a limited degree. Ten patients suffering from prurigo simplex subacuta were
      treated with foil bath PUVA at a concentration of 0.5 mg 8-methoxypsoralen/l.
      Using the foil bath method the volume of the psoralen/bath-water solution is
      restricted to 10 l with the aid of polyethylene foil. The group required a median
      of 13 (95% CI: 9-19) baths for clearance. The total UV-A dose for the whole group
      was 19 (95% CI:5-30) J/cm2. Bath PUVA is a safe and well-tolerated therapy in the
      treatment of prurigo simplex subacuta.

PMID- 8869695
TI  - Local expression of migration inhibitory factor and Th1 type cytokine mRNA in
      sporotrichosis lesions.

PMID- 8869696
TI  - Congenital ectopic nails of the fingers is associated with bone deformities.

PMID- 8869697
TI  - Climatotherapy at the Dead Sea stimulates vitamin D3 metabolism.

PMID- 8869698
TI  - Granuloma annulare: clinical and laboratory findings in a pediatric group of
      patients.

PMID- 8869699
TI  - Allopurinol therapy in post-kala-azar dermal leishmaniasis.

PMID- 8869700
TI  - Localised bullous pemphigoid following radiotherapy.

PMID- 8869701
TI  - Secondary erythermalgia in an HIV-infected patient. Is there a pathogenic
      relationship?

PMID- 8869702
TI  - Multiple facial cylindromas in twins.

PMID- 8869703
TI  - Tri-chloroacetic acid: a cause of vulvar vestibulitis.

PMID- 8869704
TI  - Conjugal chondrodermatitis nodularis helicis.

PMID- 8869705
TI  - European Association of Neurosurgical Societies. Seventeenth European Lecture.
      Taormina, Italy, February 24th, 1996.

PMID- 8869706
TI  - The surgical treatment of Chiari I malformation.
AB  - A retrospective study was undertaken on 133 patients with a Chiari I malformation
      treated within the last 16 years at the Departments of Neurosurgery at the
      Nordstadt Hospital Hannover, Germany, and the University of California, Los
      Angeles, U.S.A. Ninety-seven patients presented with symptoms related to
      accompanying syringomyelia and 4 with associated syringobulbia. They underwent
      149 surgical procedures and were followed for a mean of 39 +/- 52 months. A
      decompression at the foramen magnum was performed in 124 patients, while 22 of
      those with syringomyelia were treated by shunting (7 syringosubarachnoid shunts,
      15 syringoperitoneal or -pleural shunts), and 3 by ventriculoperitoneal shunts
      for hydrocephalus. Except for ventriculoperitoneal shunting, at least a short
      term decrease in size of an associated syrinx was observed for all procedures in
      the majority of cases. However, no long-term benefit was observed for syrinx
      shunting operations. The best clinical long-term results were obtained with
      decompression of the foramen magnum in patients with (86% free of a clinical
      recurrence) and without syringomyelia (77% free of a clinical recurrence). We
      advise against syrinx shunting, a large craniectomy, and obex plugging which are
      associated with higher recurrence rates. Instead, surgery should consist of a
      small craniectomy, opening of the dura, archnoid dissection to establish normal
      cerebrospinal fluid (CSF) outflow from the 4th ventricle, and a fascia lata dural
      graft.

PMID- 8869707
TI  - Choroid plexus papillomas: consideration of a surgical series of 33 cases.
AB  - With the aim of understanding better the behaviour of an uncommon lesion such as
      the choroid plexus papilloma, we have analysed a surgical series of 33 cases
      operated on at the Neurosurgical Department, University of Rome "La Sapienza",
      between 1955 and 1992 and have reviewed the relevant literature. Our results
      support the view that a radical resection of these lesions, which if removed
      entirely, carry a very good prognosis. The hydrocephalus should be treated only
      if persistent. Adjuvant treatment such as radiotherapy and chemotherapy should be
      reserved for specific cases.

PMID- 8869708
TI  - Cystic meningioma.
AB  - Meningiomas are usually solid tumours. Cystic changes in meningiomas are rare.
      These cysts may occur extratumoural, peritumoural or intratumoural. Diagnostic
      difficulties arise in cases of cystic meningiomas. Nine cases of cystic
      meningiomas were operated on in the past 6 years at the department of
      neurosurgery University of Alexandra. The mean age of patients was 46.2 years.
      Male to female ratio was 1/2. Less oedema was observed in extratumoural cysts,
      and more oedema in intratumoural cysts. The fluid contained was dark brown or
      dirty yellow in intratumoural cysts (type C), xanthochromic in peritumoural cysts
      surrounded by tumour tissue (Type B), or clear fluid in extratumoural cysts (Type
      A). Based on these two observations it is proposed that the cyst fluid and
      peritumoral oedema may represent variable degrees of degeneration or secretion by
      tumour cells. Pre-operatively diagnostic criteria are presented.

PMID- 8869709
TI  - Glial tumourettes (glial microtumours): their clinical and histopathological
      manifestations.
AB  - This study represents our experience with eight cases (males: 4; females: 4; 13
      47 years old, average age 28.5 years) of a "glial tumourette" (minute glioma),
      which measured less than 15 mm in diameter on an MRI. Four tumours were located
      in the frontal lobe, one in the rostrum of the corpus callosum, two in the
      midbrain, and one in the thalamus. The symptoms and signs lasted from two days to
      15 months prior to diagnosis, and they consisted of epileptic seizures in five
      patients and increased intracranial pressure due to hydrocephalus resulting from
      aqueductal stenosis in three. All patients had a CT scan and an MRI as a part of
      their initial neuroimaging evaluations. While the CT findings failed to show the
      lesion in four patients, MRI demonstrated it in all cases. Five tumours were
      either totally or subtotally removed while the remaining three were biopsied.
      Histological examinations revealed six tumours to be low-grade gliomas
      (fibrillary astrocytoma: 4; oligoastrocytoma: 2) and two to be high-grade gliomas
      (anaplastic astrocytoma: 1; anaplastic oligodendroglioma: 1). Regarding adjuvant
      therapy, three patients received radiation and/or chemotherapy. One of the
      patients with midbrain fibrillary astrocytoma died of the disease 38 months after
      the operation, however, no evidence of progression in the remaining seven has
      been observed in the follow-up period ranging from five to 65 months after the
      operation (average: 25.4 months). The histogenesis of benign and malignant
      gliomas and the importance of surgical exploration in the management of such
      patients with minute intracerebral tumours are also discussed.

PMID- 8869710
TI  - Is the outcome of traditional lumbar disc surgery related to the size of the
      exposure?
AB  - The purpose of this study was to evaluate whether wide surgical exposures result
      in poorer outcome of lumbar disc surgery compared to smaller traditional
      exposures. The aim was also to assess if a dural tear has any impact on the
      postoperative clinical outcome. One hundred and twenty-two patients (56 women and
      66 men, mean age 40.8 years) with herniated intervertebral lumbar disc and no
      previous back surgery, were included. Postoperatively they were grouped according
      to surgery as follows: surgery on one vs. two herniated discs (106 vs. 16
      patients), partial vs. full laminectomy (93 vs. 29 patients), and the occurrence
      or not of a dural rent (8 vs. 114 patients). The outcome of surgery was evaluated
      one years postoperatively mainly by a composite clinical overall score (COS) and
      by its separate elements, which were: pain intensity in the lower-back or leg
      (VAS), neurological and clinical examination, functional capacity (Oswestry), and
      the need for analgesics. The results of the statistical regression analyses did
      not reveal significant differences in the postoperative outcome scores in the
      various groups of patients. The groups were comparable; no significant
      differences were seen in the pre-operative clinical overall scores.

PMID- 8869711
TI  - Shunt malfunction in relation to shunt infection.
AB  - Ventriculo-peritoneal shunt malfunction may be caused by shunt infection which
      may not be clinically apparent as the cause of the malfunction by standard
      diagnostic criteria. This suggests that the real incidence of infected shunts
      might be higher than previously suspected. In order to study the relationship
      between infection and shunt malfunction, we followed a protocol over five years
      (54 V-P shunts) consisting of (1) removal of the malfunctioning shunt and
      replacement in the same surgical procedure with a new one or institution of an
      external ventricular drainage for 8 days (if there were clear signs of
      infection), (2) culturing of CSF and every part of the removed shunt, and (3)
      intravenous antibiotic treatment (Vancomycin 1g./12h + Ceftriaxone 1g./12h) for
      five days after the new V-P shunt had been inserted. In those cases in which an
      external ventricular drainage had been placed, its tip and a portion of the new V
      P shunt were also cultured. The results showed that although CSF cultures were
      negative in 49/54 cases (90.7%), cultures of the removed shunts were positive in
      32/54 (59.2%), most of them (21/32, 65.6%) for Staphylococcus coagulase negative
      organisms. The CSF samples obtained by puncturing the reservoir on admission to
      Hospital were positive only in 5 out of 54 cases (9.2%), only in those showing
      clinical features of infection. In the remaining cases, 27 out of 54 (50%) the
      CSF cultures were negative but the shunt cultures proved positive and required
      further treatment. For the newly inserted shunts (173) CSF was collected through
      the shunt during the surgical procedure, and a small piece of the extra-tube from
      the ventricular and from the peritoneal catheter were obtained and cultured. All
      the six shunts (6/173, 3.4%) that showed positive cultures after insertion had to
      be replaced within a period of three to four weeks due to malfunction (range 26
      +/- 7 days), indicating that the systematic culture of CSF and tubing helps to
      predict which shunts will soon need to be replaced due to infection. We conclude
      that CSF culture alone does not rule out infection in cases of shunt malfunction.
      The percutaneous CSF obtained from the shunt reservoir admission is particularly
      prone to show negative cultures even when the shunt is colonized by bacteria.

PMID- 8869712
TI  - Short course antimicrobial therapy in intracranial abscess.
AB  - In this study, the author attempts to question the necessity of prolonged
      antimicrobial treatment for intracranial abscess. The C reactive protein (CRP)
      was measured serially in 26 patients with intracranial abscess. All patients had
      undergone surgery and were treated with antimicrobial therapy. The CRP was
      elevated in 20 (77%) patients and its return to normal after treatment correlated
      with a good recovery. In 3 (12%) patients a persistently high CRP level
      postoperatively coincided with reformation of the abscess. A transient rise in
      the CRP value during decrease to normal was due to deep venous thrombosis in 2
      (8%) patients. The return of the CRP to normal in conjunction with improvement of
      the patient's clinical condition and evidence of resolution of the abscess on CT
      scan were used as a guideline to stop antibiotics early. The antimicrobial
      therapy of the patients in this series ranged from 11-30 (mean 20) days and the
      follow up from 6-36 (median 21) months; there have been no recurrences.

PMID- 8869714
TI  - Posterior communicating artery section during surgery for basilar tip aneurysm.
AB  - Although dividing the posterior communicating artery (PComA) during surgery has
      been criticized for increasing the risk of ischaemia, this procedure increase
      working space improving visibility and the ability to manipulate during treatment
      of basilar tip aneurysms via the pterional approach. We divided a hypoplastic
      PComA in 4 of our cases of basilar tip aneurysm. This was necessary because
      either (1) the length of the PComA and intracranial internal carotid artery (ICA)
      limited medial retraction of the ICA and access to the basilar bifurcation
      region, or (2) the PComA and its perforators ran just in front of the aneurysm,
      interfering with its exposure. We were able to clip the aneurysm neck in all four
      patients, three of whom had complications including temporary impairment of
      consciousness, ocular movement disorders and altered sensation in the
      extremities. Patients with complications showed transient hypersomnolence
      immediately after surgery; computed tomography showed small thalamic infarctions.
      However, in two of three patients the ischaemic events occurred contralateral to
      the side of PComA section. All patients regained consciousness within a week and
      were discharged with mild ocular movement palsies. In our cases except one with
      ischaemic complications, thalamic infarction probably resulted from thalamo
      perforating artery injury when the aneurysm neck was clipped, rather than
      tuberothalamic artery injury due to section of the PComA. Taking previous reports
      and our results into consideration, we believe that division of a hypoplastic
      PComA is a safe procedure in particular cases when the grade of subarachnoid
      haemorrhage is not poor and there are no cerebrovascular risk factors, although
      we realize it is desirable to preserve normal blood flow.

PMID- 8869713
TI  - Aneurysms of the posterior cerebral artery: do they present specific
      characteristics?
AB  - A series of 7 cases of PCA aneurysm treated between 1978 and 1992 were
      analytically reviewed together with 79 cases culled from the literature. In
      comparison to those localized elsewhere, PCA aneurysms are more frequently large,
      more frequently present with tumour-like symptoms and appear at an earlier age.
      Surgical outcome was evaluated in relation to clinical onset, site and size of
      the aneurysm, the surgical procedures adopted for excluding it and pre-operative
      clinical grading appeared to influence outcome. The fact that site, size and
      surgical technique do not significantly influence prognosis is probably due to
      the rich collateral flow present in the areas fed by the posterior cerebral
      artery. The authors conclude that, clinically speaking, PCA aneurysms should be
      considered as a separate group.

PMID- 8869715
TI  - Experimental hydrocephalus and hydromyelia: a new insight in mechanism of their
      development.
AB  - One group of cats had an acrylic screw implanted into the adqueduct of Sylvius,
      while the other group of animals received a solution of kaolin into the cisterna
      magna. Three weeks later the dye phenolsulphonphthalein was instilled into the
      lateral ventricle to ascertain communication between CSF compartments, and
      thereafter the brain was perfused with formalin. As shown by planimetry of brain
      ventricles both groups of experimental animals developed hydrocephalus, i.e.,
      coronal surface of brain ventricles was about 10 times larger in kaolin and about
      3 times in aqueductal screw experiments than in the controls, respectively. In
      aqueductal screw experiments communication of CSF between lateral ventricle and
      subarachnoid spaces was not blocked but only restricted, i.e., an aqueductal
      stenosis was produced. In kaolin experiments communication of CSF between lateral
      ventricles and spinal subarachnoid space was blocked by thick meningeal adhesions
      in the upper cervical region, while the central spinal canal was dilated
      (hydromyelia) with enhanced CSF communication between it and the lumbar
      subarachnoid space. We assume that during systolic expansion of brain the CSF is
      displaced from the cranial cavity toward the spinal subarachnoid space which
      accommodates an additional volume of CSF primarily due to compliance of the
      spinal dural sac, while during diastole CSF recoils in the opposite direction.
      Thus, in case of aqueductal stenosis the undisplaced volume of CSF from the
      ventricles can be accommodated due to diminution of cerebral blood volume and
      brain parenchyma so that hydrocephalus develops over time. Since the cervical
      subarachnoid space is blocked in kaolin experiments the systolic brain expansion
      forces CSF from basal cisterns via the fourth ventricle into the aqueduct and
      central canal with consequent development of hydrocephalus and hydromyelia.

PMID- 8869716
TI  - Nitric oxide synthase is expressed in experimental malignant glioma and
      influences tumour blood flow.
AB  - The distribution and function of nitric oxide synthase (NOS) was studied in the
      rodent C6 implantation glioma model. Using a histochemical stain for NADPH
      diaphorase, which colocalises with NOS, morphological studies revealed non
      homogenous staining of the constituent tumour cells and the neoplastic
      endothelium. Immunocytochemical staining for macrophages (ED1, ED2) showed dense
      positivity at the tumour brain interface with more patchy positivity within the
      tumour mass. This finding suggests that both macrophages, which are known to
      produce large amounts of NO, and the C6 cells contribute to the NADPH diaphorase
      positivity. Administration of the NOS inhibitor Ng-nitro-L-argine methyl ester (L
      NAME) significantly reduced both tumour (40%) and contralateral local cerebral
      blood flow (20%) compared to control animals. These findings demonstrate that (i)
      NOS is present in experimental malignant glioma; (ii) NO mediated mechanisms
      contribute to tumour blood vessel dilatation and blood flow regulation; and (iii)
      using this model there is a significant differential sensitivity of the tumour
      and brain parenchymal vascular beds to a NOS inhibitor. Further investigations
      are required to determine the potential therapeutic and biological relevance of
      these findings and the relative contributions of tumour cells, neoplastic
      endothelium and reactive macrophages to NO mechanism in gliomas.

PMID- 8869717
TI  - The role of angiogenic factor bFGF in the development of dural AVFs.
AB  - PURPOSE: Dural arteriovenous fistulas (dAVFs) are known to be acquired disorders.
      Angiogenic stimulants, such as basic fibroblast growth factor (bFGF), may be
      involved in the evolution of this disorder. We examined the appearance and
      localization of bFGF, in human dAVF sinuses, versus a control using
      immunohistochemical techniques, to evaluate these qualitative differences.
      PATIENTS AND METHODS: Four human dural sinuses from dAVF patients, and one
      control dural sinus were removed at surgery or autopsy and used for this study.
      Immunohistochemistry for bFGF was performed in all five specimens to identify its
      appearance and localization. Immunohistochemistry for alpha smooth muscle actin,
      factor VII related antigen, and macrophage (CD-68) were done in all tissues to
      identify the bFGF positive cell types. RESULTS: In the control dural sinus, there
      was negative staining by bFGF immunohistochemistry. However, in all four sinuses
      of the dAVF patients, smooth muscle cells, endothelial cells, and meningeal cells
      were stained positively in various degrees by bFGF immunohistochemistry.
      CONCLUSION: bFGF may be significant in the development of dAVFs, judging from its
      strong immunoreactivity in the sinuses of dAVF patients.

PMID- 8869718
TI  - A systemic "dumb-bell" haemangiopericytoma.
AB  - Systemic haemangiopericytoma is a rare soft tissue tumour originating from
      pericytes which are contractile pericapillary cells, and represents less than one
      percent of all vascular neoplasms. The most common site of involvement is the
      thigh followed by the retroperitoneum, while the paraspinal location is very
      rare. We report the first case of systemic "dumb-bell" haemangiopericytoma
      illustrated radiologically, which mimick, a dorsal "dumb-bell" neurinoma.

PMID- 8869719
TI  - Thoracic meningioma presenting subarachnoid haemorrhage.

PMID- 8869720
TI  - Syringomyelia with basilar impression in osteogenesis imperfecta.

PMID- 8869721
TI  - Exophytic cavernous malformation of the cervical spinal cord.

PMID- 8869722
TI  - Giant cell arteritis with subarachnoid haemorrhage due to the rupture of
      inflammatory aneurysm of the posterior inferior cerebellar artery.

PMID- 8869723
TI  - Hsp70 expression in human skeletal muscle after exercise.
AB  - Prolonged exercise of a sufficiently high intensity is thought to create
      physiological stress and to disturb cellular homeostasis, ultimately inducing
      cellular adaptations which enable the organism to better deal with any future
      exercise challenge. Heat shock proteins (hsp) are expressed when cells are
      exposed to different types of stress. In this study, we have investigated whether
      the expression of the heat inducible form of hsp70 is increased in human skeletal
      muscle cells after a single bout of exercise. Five untrained subjects performed
      an exercise bout at their individual anaerobic threshold for 30 min on a
      treadmill. Hsp70 mRNA concentration was significantly increased by a factor of
      four at 4 min post-exercise. Similarly high levels were also observed 30 min and
      3 h after the end of exercise. Hsp70 protein concentration, on the contrary, did
      not change within 3 h after cessation of exercise. Thus, a single exercise bout
      in humans is able to increase the steady state concentration of hsp70 mRNA, but
      is probably not sufficient to have an effect on the already high basal level of
      its protein. The analysis of hsp70 mRNA is potentially useful as a method to
      detect stress in tissues with a high basal level of heat shock proteins.

PMID- 8869724
TI  - Differentiated effects of vasodilators on myogenic reactivity during partial
      inhibition of myogenic tone in pressurized skeletal muscle small arteries of the
      rat.
AB  - Myogenic tone and reactivity were studied in isolated, cannulated and pressurized
      small branches of the femoral artery of the rat. Myogenic tone developed
      spontaneously under control conditions (1.5 mM Ca2+), reducing the diameter at 80
      mmHg to 64 +/- 6% of the 'max 80', i.e. the diameter in Ca2+ free solution, which
      was 221 +/- 23 microns (mean +/- SD, n = 18). The calcium channel blockers
      verapamil and diltiazem, dose-dependently, decreased this myogenic tone with
      pIC50 values of 6.9 +/- 0.2 (n = 7) and 6.6 +/- 0.1 (n = 6), respectively.
      Myogenic reactivity was demonstrated under control conditions as a sustained
      decrease in diameter, by 5 +/- 3% of max 80 (after an initial, transient
      distension), in response to a step increase in transmural pressure from 80 to 140
      mmHg. This response to the pressure increase was markedly inhibited when myogenic
      tone had been reduced by 50% with verapamil or diltiazem resulting, in fact, in
      an increased steady state diameter by 2 +/- 1 and 1 +/- 1% at 140 compared with
      80 mmHg. However, if myogenic tone was reduced to the same extent by low
      extracellular Ca2+ (approximately 0.3 mM) the vessels constricted by 6 +/- 1% in
      response to the pressure increase, an effect comparable to that in control Ca2+.
      Moreover, 50% reductions in myogenic tone by ACh (approximately 0.1 microM) or
      pinacidil (approximately 0.3 microM) were associated with significantly enhanced
      reactivity; steady state diameter decreased by as much as 11 +/- 4 and 15 +/- 5%
      of max 80. These results suggest that voltage dependent L-type Ca2+ channels are
      involved both in myogenic tone and in the myogenic response to a rise in vascular
      transmural pressure in skeletal muscle arteries. Partial inhibition of myogenic
      tone by other pharmacological routes do not necessarily interfere with myogenic
      reactivity since the response was, in fact, enhanced in the presence of ACh or
      pinacidil.

PMID- 8869725
TI  - Muscle glycogen repletion from endogenous carbon sources during recovery from
      high intensity exercise in the fasted rat.
AB  - During recovery from high intensity exercise, substantial and rapid muscle
      glycogen repletion from endogenous carbon sources is reported in a variety of
      vertebrate species, the rat being the only reported exception. The major aim of
      this study was to re-examine the process of glycogen repletion during recovery
      from high intensity exercise in the rat. In response to 3 min of vigorous
      swimming, muscle glycogen concentrations decrease markedly from initial levels of
      20.2 +/- 1.5 and 21.2 +/- 0.9 mumol g-1 to 6.4 +/- 1.1 and 7.9 +/- 1.4 mumol g-1
      in the tibialis anterior and plantaris muscles respectively. The equivalent of
      58% of the glycogen carbons mobilized during exercise by the plantaris and 73% of
      that mobilized by the tibialis anterior muscle is repleted within 1 h following
      exercise. Using the hepatectomized rat as experimental model, a secondary aim of
      the study was to evaluate whether the liver is essential for the repletion of
      muscle glycogen. Although the absence of significant differences in the magnitude
      of post-exercise muscle glycogen repletion between sham-operated and
      hepatectomized rats suggests that the resynthesis of muscle glycogen can take
      place in the absence of hepatic gluconeogenesis, the present study identifies
      several limitations in the use of acute hepatectomy. Overall, the present study
      indicates that, in contrast to published views, the rat resembles other
      vertebrates in that it can support extensive muscle glycogen repletion from
      endogenous carbon sources during the recovery phase following high intensity
      exercise.

PMID- 8869726
TI  - Anaerobic capacity and maximal oxygen uptake during arm stroke, leg kicking and
      whole body swimming.
AB  - In the present study, we determined both anaerobic capacity (the maximal
      accumulated oxygen deficit) and maximal oxygen uptake (VO2max) during arm stroke
      (A), leg kicking (K), and whole body swimming (S), and compared them. The
      subjects were six trained college swimmers (two male and four female), aged 20 +/
      1 years. To determine VO2max for A, K and S, VO2max was measured during a 6-min
      swim at constant water flow rates. VO2 was measured by the Douglas bag method.
      Anaerobic capacity was determined by accumulated oxygen deficit during exercise
      lasting 2-3 min according to the methods of Medbo et al. Mean values of VO2max
      during A, K and S were 2.53 +/- 0.37 L min-1, 2.93 +/- 0.37 L min-1, and 3.23 +/-
      0.43 L min-1, respectively. Those in A and K corresponded to 78.2% and 91.0% of
      that in S. Mean values of anaerobic capacity during A, K and S were 2.15 +/- 0.31
      L, 2.52 +/- 1.08 L and 2.99 +/- 0.52 L, respectively. Those in A and K
      corresponded to 73.3% and 81.7% of that in S. Both VO2max and anaerobic capacity
      in S were much lower than the sum of A and K, corresponding to only 59.3% and
      65.9%, respectively. These results suggest that the total energy production
      during S is lower than simply the sum of A and K because the potentials of both
      the anaerobic and aerobic energy releasing processes in the muscle groups
      involved in A and K cannot be fully reached during S.

PMID- 8869728
TI  - Endothelin-1 causes a prolonged protein kinase C activation and acts as a co
      mitogen in vascular smooth muscle cells.
AB  - Endothelin-1 (ET-1) is known to act via G-protein coupled receptors. It has
      therefore been suggested that any mitogenic activity it may possess, is due to
      activation of phospholipase C and protein kinase C (PKC). We have therefore
      examined both the ability of ET-1 to act as a mitogen and its ability to activate
      PKC. We found that ET-1 significantly increased thymidine incorporation and
      enhanced platelet-derived growth factor-induced DNA synthesis, as well as causing
      a prolonged translocation of PKC to the cell membrane. ET-1 significantly
      increased PKC dependent phosphorylation of two specific substrates. The
      phosphorylation of MBP4-14 (from myelin basic protein) was partially dependent on
      extracellular Ca2+, implicating activation of PKC-alpha, whereas phosphorylation
      of the so called epsilon-peptide was Ca(2+)-independent and prolonged. This could
      be due either to the delta or zeta isoform of PKC, known to be present in these
      cells. However, ET-1 induced little proliferation of PKC activity in a
      transformed smooth muscle cell line, DDT1 MF-2, which lacks expression of the PKC
      alpha isoform, but expresses the zeta-isoform. Thus, it would appear the ET-1
      induced mitogenicity in smooth muscle cells may be related to the sustained,
      Ca(2+)-independent activation of PKC-delta.

PMID- 8869727
TI  - Acute mental stress but not enforced muscle activity transiently increases
      natural cytotoxicity in spontaneously hypertensive rats.
AB  - The influence of acute mental stress and the effect of electrically induced
      skeletal muscle contractions on natural cytotoxicity in vivo was investigated in
      spontaneously hypertensive rats Natural cytotoxicity in vivo was measured as the
      clearance of injected 51Cr-labelled YAC-1 lymphoma cells from the lungs, which
      are specifically lysed by natural killer cells. The mental stress consisted of an
      air jet directed towards the animals in their cage for 25 min. During the mental
      stress there was a significant increase in natural cytotoxicity. Thus, retained
      radioactivity in the lungs was decreased to 74 +/- 6% of the control levels which
      was set to 100% (P < 0.01). This augmentation of YAC-1-cell clearance could be
      blocked with the beta-adrenergic receptor antagonist Timolol. Two hours after
      termination of the air stress, in vivo cytotoxicity had returned to control
      levels. In contrast, acute physical stress, consisting of electrically induced
      muscle contractions for 60 min, had no significant effects on in vivo
      cytotoxicity, either during the stimulation or 1, 2 or 24 h after the
      stimulation. Further, significantly increased plasma levels of adrenaline were
      seen after the air jet stress, but not after muscle stimulation. There were no
      significant changes in plasma noradrenaline levels either after air stress or
      muscle stimulation. These results indicate that changes in in vivo cytotoxicity
      after mild mental stress are dependent on increased plasma catecholamine levels
      while acute physical stress without changes in catecholamine levels, does not
      influence in vivo cytotoxicity.

PMID- 8869729
TI  - Progesterone, oestradiol and oxytocin and their in vitro effect on maintaining
      the number of gap junction plaques in human myometrium at term.
AB  - Previous studies by electron microscopy and laser confocal microscopy of
      immunohistochemically stained sections have shown that during pregnancy the
      extent of gap junction formation in human myometrium is low, but that an increase
      occurs in the active stages of labour despite a high concentration of
      progesterone in maternal blood. The present investigation focused on the effect
      of in vitro exposure of isolated myometrial tissue to progesterone, oestradiol
      and oxytocin, on the number of gap junction plaques in human myometrium at term.
      Myometrial biopsies were obtained at term from 13 pregnant women who had an
      elective caesarean section in the 37th or 40th week of pregnancy. The biopsies
      were immersed immediately in Hepes buffer and buffer containing 0.5, 5.0
      micrograms mL-1 of progesterone, and 0.1 micrograms mL-1 of oestradiol. The
      muscle biopsies were trimmed under a stereo microscope into strips along the
      bundles of smooth muscle cells and mounted in tissue baths, superfused with Hepes
      buffer supplemented with glucose (0.01 mM); subsequently the strips were exposed
      to buffer containing different concentrations of progesterone, oestradiol and
      oxytocin. Incubation of the muscle strips for 180 min resulted in a significant
      decrease of the number of gap junctions (P < 0.01). Neither oestradiol or
      oxytocin, alone or in combination, had a significant effect on the maintenance of
      the number of gap junctions. The progesterone concentration of 5.0 micrograms mL
      1, combined with oxytocin, and with or without oestradiol has a significantly
      positive effect on the number of gap junction plaques in strips of human
      myometrium at term (P < 0.05 vs. buffer alone). The high concentration of
      progesterone in the superfusion medium during in vitro experiments may be
      responsible for the maintenance of high numbers of gap junction complexes in term
      human myometrium. This finding is of interest in the light of findings of
      persisting high progesterone levels in maternal blood during labour.

PMID- 8869731
TI  - Atrial plasma ANP and NH2-terminal proANP during right atrial pressure increase
      in humans.
AB  - To compare plasma NT-proANP, a stable and biologically inactive N-terminal
      portion of ANP prohormone, with the known plasma ANP response to increased right
      atrial pressure a Swan-Ganz catheter was inserted into the right atrium of five
      normal healthy male volunteers. The elevation of right atrial pressure was
      produced by a head-down tilt after a hypertonic saline infusion. Blood samples
      were drawn from the lumen of the right atrium. After 5 min of starting the tilt
      the right atrial pressure had increased from 7.0 +/- 1.0 to 11.6 +/- 0.9 mmHg (P
      < 0.05) and then began to normalize in spite of the constant tile. Atrial plasma
      ANP increased in relation to the pressure increase and peaked at 15 min after the
      start of the tilt. The change was from 27.9 +/- 6.5 to 53.9 +/- 9.7 pmol L-1 (P <
      0.05). Atrial plasma NT-proANP increased significantly from 357 +/- 91.2 to 529.1
      +/- 116.0 pmol L-1 (P < 0.05) at 10 min and remained high throughout the
      experiment. The molar ratio of NT-proANP to ANP varied in atrial plasma from 9.5
      +/- 1.2 to 13.9 +/- 2.7 showing that the plasma clearance of ANP from plasma was
      much higher than that of NT-proANP.

PMID- 8869730
TI  - Endogenous nitric oxide as a physiological regulator of vascular tone in cat
      skeletal muscle during haemorrhage.
AB  - The problem whether endogenous nitric oxide (NO) may serve as a true
      physiological regulator of vascular tone in vivo was approached by testing its
      role during graded acute haemorrhage with the aid of the nitric oxide synthase
      (NOS) inhibitor L-NAME. The study was performed on the vascular bed of cat
      skeletal muscle with a technique permitting quantitative recordings of vascular
      resistance in the whole vascular bed (RT) and in its consecutive sections, the
      proximal arterial resistance ('feeder') vessels (> 25 microns; Ra,prox), the
      small arterioles (< 25 microns) and the veins. NO blockade by close-arterial L
      NAME infusion in the control situation increased RT from 16.3 to 33.0 PRU
      (+102%), because of a selective increase in Ra,prox by 16.7 PRU. A 35% blood loss
      per se raised RT from 13.6 to 21.7 PRU. Superimposed NO blockade in this state
      caused a much stronger vasoconstriction than in the control situation, increasing
      RT to 60.9 PRU (+181%) and Ra,prox by 40.5 PRU, which indicated an approximately
      2.4-fold increase (P < 0.001) in the NO dilator influence in the Ra,prox section
      above control. The effect was independent of autonomic nerves. The increased NO
      dilator influence during haemorrhage most likely was caused by an increased
      production of endothelium-derived nitric oxide (EDNO), The constrictor response
      to L-NAME was graded in relation to the blood loss (17.5 vs. 35%). The results
      indicate that EDNO functions as a physiological regulator of vascular tone in the
      arterial 'feeder' vessels during haemorrhage, serving to counterbalance to a
      significant extent the concomitant adrenergic constriction, and thereby
      preventing critical reduction of blood flow and untoward heterogeneous flow
      distribution within the tissue.

PMID- 8869732
TI  - The fade of gastrin-stimulated gastric acid secretion in the rat is due to
      depletion of releasable mucosal histamine.
AB  - The present study examines the applicability of the isolated, acid-secreting
      vascularly perfused rat stomach for long-term physiological and pharmacological
      studies. The model was used to study the fade of acid secretion during gastrin
      stimulation. The stomachs were stimulated by exogenous gastrin or histamine alone
      or in succession. Acid secretion and venous histamine concentrations were
      measured. Gastrin and histamine potently stimulated acid output, histamine
      stimulated acid secretion was sustained for 300 min while gastrin-stimulated
      secretion peaked at 120 min and declined towards basal output at 300 min.
      Stomachs rendered tachyphylactic to gastrin could be re-stimulated by exogenous
      histamine. Venous histamine output during gastrin stimulation decreased in
      parallel to acid secretion. This, the acid-secreting, isolated vascularly
      perfused rat stomach can be used for physiological and pharmacological studies
      with histamine as stimulant for at least 300 min. The present results strongly
      indicate that the effect of gastrin on acid secretion is mediated by histamine,
      and that fade of acid secretion during stimulation with gastrin is due to
      depletion of releasable mucosal histamine.

PMID- 8869733
TI  - Analysis of leak current properties in the lobster stretch receptor neurone.
AB  - Experiments were performed to characterize the so-called leak current of the
      slowly adapting stretch receptor neurone of the European lobster with respect to
      its ionic basis, its kinetics and its pharmacology. Estimates of the leak current
      were obtained by subtraction of a Na-K pump current and of an unspecific
      impalement current from a non-dynamic ('instantaneous') current, recorded in a
      voltage range from approximately -120 to approximately -30 mV, after blockage of
      spike-generating currents and a hyperpolarization-activated inwardly rectifying
      current (Q-current). The leak current, estimated in this way, was seen to reverse
      direction at the cell's K+ equilibrium voltage, thus indicating that it is
      carried by K+ passing through channels which, also, proved to be permeable to Rb+
      and NH4+, but not permeable to Na+ or Cl- to any significant extent. Kinetically,
      the leak current was found to be characterized by being enhanced by increases in
      extracellular K+ and by being subject to outward rectification, most distinctly
      at elevated extracellular [K+]. In quantitative terms, these kinetic properties
      could be accounted for by a mathematical model comprising (1) a one-site two
      barrier Eyring formulation describing ion permeation through membrane channels
      and (2) an ordinary dose-response relationship describing the channel-opening
      effect of K+ at an extracellular regulatory site. Pharmacologically, the leak
      current proved to be distinguished by being reversibly blockable, in a non
      voltage dependent manner, by CO2+ (Kd = 0.9 mM, Hill coefficient 1.1) and
      procaine, but not by Ba2+, Gd3+, bupivacaine (a local anesthetic), or other K+
      channel blockers such as TEA, 4-AP and Cs+. It is concluded that, in native
      unimpaled cells, the K+ carried leak current (1) is setting the resting voltage
      together with the (mainly) Na(+)-carried Q-current and the Na-K pump current, (2)
      is determining the cell's firing threshold, together with the spike generating
      currents, and (3) is also stabilizing the cell's membrane excitability in
      conditions of varying extracellular [K+], by virtue of its K+ sensitivity.

PMID- 8869734
TI  - Supplementation with ubiquinone-10 causes cellular damage during intense
      exercise.

PMID- 8869735
TI  - Thinning of the capillary endothelium with physical activity shortens the
      diffusion distance of the pulmonary air-blood barrier.

PMID- 8869736
TI  - NADPH diaphorase activity is asymmetrically distributed in the optic tectum
      during the period of eye migration in turbots.

PMID- 8869737
TI  - Differences in the properties of mammalian ribonucleotide reductase toward its
      substrates.
AB  - These studies, using three different reagents, show that the substrate properties
      of ribonucleotide reductase are specific but can be variable depending upon the
      nature of the interaction of the reagent with the holoenzyme or the individual
      subunit. Etheno-CDP, which acts as a competitive inhibitor with respect to CDP,
      interacts with the active site of the holoenzyme. This interaction was the result
      of rather tight structural requirements as epsilon-ADP did not result in a
      similar level of inhibition of either CDP or ADP reductase activities. The YL 1/2
      antibody which binds very tightly to the NHI subunit has a much greater effect on
      CDP reductase activity than ADP reductase activity. The nonapeptide that
      corresponds to the C-terminus amino acid sequence of the NHI subunit and which
      binds to the EB subunit and aborts the formation of the NHI-EB active complex has
      a greater effect on ADP reductase activity than on CDP reductase activity. The
      use of reagents such as these can be helpful in dissecting the subtle but
      important differences in the substrate properties of mammalian ribonucleotide
      reductase.

PMID- 8869738
TI  - The function of the multidrug resistance proteins (MRP and cMRP) in drug
      conjugate transport and hepatobiliary excretion.
AB  - The MRP gene encodes a 190-kDa integral membrane glycoprotein which functions as
      a primary-active ATP-dependent export pump for amphiphilic anions. The MRP gene
      encoded conjugate export pump and its canalicular isoform represent the transport
      activity which has been described earlier as multispecific organic anion
      transporter, non-bile acid organic anion transporter, glutathione S-conjugate
      export pump, or leukotriene export pump. Analyses of the substrate specificity of
      the human MRP pump were performed in plasma membrane vesicles from MRP
      overexpressing drug-selected cells (7) and cells transfected with an MRP
      expression vector (8). Substrates for MRP include thioether-linked conjugates of
      lipophilic compounds with glutathione, cysteinyl glycine, cysteine, and N-acetyl
      cysteine, but also glutathione disulfide, and glucuronate conjugates such as
      etoposide glucuronide. This broad-specificity ATP-dependent export pump is not
      only overexpressed in several multidrug resistant tumor cells and tissues, but is
      also present in most normal cells and tissues. The expression of cMRP and MRP in
      human liver and of cMrp and its homolog Mrp in rat liver was demonstrated by
      reverse transcription PCR, cDNA sequencing, and immunoblotting (13). The
      important function of the cMRP gene-encoded broad-specificity conjugate export
      pump in hepatobiliary excretion is illustrated by the selective absence of this
      canalicular isoform from the hepatocyte canalicular membrane in transport
      deficient mutant rats. This altered lack of cMrp is the basis for the hereditary
      detect of the hepatobiliary excretion of anionic conjugates in the mutant animals
      (13). The absence of this canalicular Mrp in the mutants is analogous to the
      defect in the human Dubin-Johnson syndrome which is characterized by an impaired
      excretion of conjugated anions across the canalicular membrane.

PMID- 8869739
TI  - Current issues in the regulation of signal transduction.
AB  - (1) In all examined rat and human tissues and cells, PIP kinase activity was rate
      limiting and PLC activity was present in great excess. (2) The steady-state
      activities of the signal transduction enzymes, PI kinase, PIP kinase and PLC, and
      the concentration of the end product, IP3, were determined in rat liver and
      hepatomas of different malignancies. The activities of all three enzymes were
      elevated in the hepatomas in a non-random fashion. A generalization emerged that
      the enzyme with the lowest activity in liver, PIP kinase, increased to the
      highest extent and the enzyme with the highest activity in liver, PLC, increased
      to the smallest extent in rapidly growing hepatomas. The IP3 concentration in the
      hepatomas was elevated in a progression-linked fashion. (3) The three signal
      transduction enzyme activities were elevated in human ovarian carcinoma samples
      and in human breast carcinoma cells. (4) When human breast carcinoma MDA-MB-435
      cells were allowed to go through lag, log and plateau phases, the IP3
      concentration reached a 20-fold peak at 12 hr after plating. The elevation in IP3
      concentration preceded the rise in PI and PIP kinase activities which increased
      11-fold in the log phase. The IP3 concentration and PI and PIP kinase activities
      returned to their baseline levels when the plateau phase was reached. The PLC
      activity did not change significantly during the whole period. (5) Administration
      of cycloheximide i.p. in rats revealed short half-lives in the bone marrow for
      the two kinases (8 min) and a long half-life for PLC (> 6 hr). In a group of 10
      enzymes, the half-lives of the kinases were the shortest. In cycloheximide
      injected rats, the bone marrow IP3 concentration was reduced to about 50% in 30
      min. The reduction of IP3 concentration is attributed to the decline to 15 and
      12%, respectively, in PI and PIP kinase activities since PLC activity did not
      change. (6) In 3-day starved rats, the bone marrow PI and PIP kinase were reduced
      to activities (13%) that were markedly lower than the decrease in the protein
      concentration (to 55%). By contrast, the PLC activity was preferentially
      maintained (to 78%) over the protein level. Under starvation, the IP3
      concentration decreased (to 24%), indicating that starvation can markedly disrupt
      IP3 homeostasis. Refeeding returned the enzymic activities and the IP3
      concentration to the normal level in bone marrow in 24 hr. (7) Comparison of the
      absolute activities of PI and PIP kinases and PLC showed that PLC is present in
      an excess; therefore, it does not appear to have a rate-limiting action in
      cycloheximide treated rats or in starvation. (8) Whereas PI and PIP kinases have
      short half-lives and apparently rapid synthetic rates, PLC has high activity, a
      long half-life and responds to starvation with only a small decrease. (9) The
      gain in function manifested in the over-expressed capacity for signal
      transduction confers growth advantages to cancer cells. These increased
      activities, particularly those of PI and PIP kinases, should be sensitive targets
      for chemotherapy.

PMID- 8869740
TI  - Mechanism and structure based inhibitors of phospholipase C enzymes.
AB  - PI-specific PLC enzymes are a key component of phosphatidylinositol-mediated
      signaling pathways since the hydrophobic product, diacylglycerol, activates
      protein kinase C and the water-soluble product, inositol trisphosphate, is
      involved in Ca2+ mobilization. Nonspecific, or PC-PLC, enzymes can generate
      diacylglycerol without Ca2+ mobilization. A series of inhibitors, both lipophilic
      and water-soluble, have been synthesized to target each of these two classes of
      PLC enzymes. Design of the inhibitors was based on proposed enzyme mechanisms and
      available crystal structures. The solution conformations of the lipophilic
      phospholipid analogs, (diheptanoylphosphatidyl(2-O-methyl)inositol for PI-PLC and
      a dihexanoyl-sn-(3-N-benzylaminoglycero)phosphoramidocholine for PC-PLC, have
      been determined using NMR methodology and the interaction of these compounds with
      bacterial enzymes has been examined. Water-soluble inhibitors include strained
      cyclic phosphonates for PI-PLC and vanadate for PC-PLC. An eventual goal of this
      work is to generate compounds that specifically target each type of intracellular
      PLC activity.

PMID- 8869741
TI  - Inosine monophosphate dehydrogenase expression: transcriptional regulation of the
      type I and type II genes.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is an essential rate-limiting
      enzyme in the de novo guanine nucleotide synthetic pathway that catalyzes the
      conversion of IMP to XMP. Enzyme activity is accounted for by the expression of
      two distinct but closely related genes termed IMPDH I and II. Increased IMPDH
      activity has been linked to both cellular proliferation and neoplastic
      transformation and generally ascribed to an increase in the expression of the
      type II gene. We have characterized the type I and type II genes and identified
      elements important in the transcriptional regulation of both genes. The type II
      IMPDH gene contains a 466 bp 5' flanking region spanning the translation start
      site that contains several transcription factor binding sites and mediates
      increased transcription of a CAT reporter gene in peripheral blood T lymphocytes
      when these cells are induced to proliferate. The single functional IMPDH type I
      gene contains exon-intron boundaries and exon structures that are nearly
      identical to those in the type II gene. In contrast to the type II gene, however,
      it contains two putative promoter sites, each with the potential for
      transcriptional regulation. We conclude that these two genes most probably arose
      from an early gene duplication event and that their highly conserved structures
      and differential regulation at the transcriptional level argue strongly for a
      significant role for each gene in cellular metabolism, growth, and
      differentiation.

PMID- 8869742
TI  - Regulation of the human bilirubin UDP-glucuronosyltransferase gene.
AB  - The human UGT1 gene is a single copy gene consisting of four common exons and
      more than 13 variable exons which span more than 200 kb of the human genome. A
      single variable exon is spliced to the four common exons to form the mRNA for
      synthesis of a single UDP-glucuronosyltransferase (UGT) isoenzyme. Treatment of
      humans or hepatoma cell lines with drugs such as phenobarbital causes the
      induction of hepatic bilirubin UGT by increased transcription from the UGT1 gene.
      The upstream region of UGT1*1 (bilirubin UGT) was sequenced and found to contain
      consensus sequences for several transcriptional regulatory elements including a
      'BARBIE box'. An unusual 'TATA' promoter sequence A(TA)6TAA was also observed.
      The 5' region flanking the UGT1*1 exon when cloned into reporter constructs and
      transfected into four cells lines was capable of promoting reporter gene
      expression, but not when transfected into monkey kidney cell fibroblasts (COS-7
      cells) indicating a cell specific expression. Sequential deletion of the 5'
      flanking region in the plasmid constructs did not cause any significant reduction
      in reporter expression. Treatment of cells transfected with these plasmid
      constructs with drugs did not cause a significant increase in reporter expression
      except with retinoic acid plus WY 14643. Introduction of an additional two base
      pairs (TA) into the 'TATA' box of the 5' gene sequence (as observed in Gilbert's
      patients) did not significantly change reporter expression levels. The regulation
      of the biliruibin UGT gene by drugs is not yet understood and it will be
      important to identify additional genetic elements possibly further than -2kb
      upstream of the UGT1*1 coding region, which regulate the expression of this gene.

PMID- 8869743
TI  - Inositol lipid cycle and autonomous nuclear signalling.
AB  - The involvement of phospholipids and in particular polyphosphoinositides in
      cellular signalling has been documented in detail in the last 20 years. In
      addition to the plasma membrane localization also the nucleus is shown to be a
      site for both synthesis and hydrolysis of the phosphorylated forms of
      phosphatidylinositol. Previous observation have established that the nucleus
      possesses a specific PLC for inositol lipids, i.e., the PLC beta 1 isoform, which
      undergoes rapid and transient activation after IGF-I stimulation of quiescent
      Swiss 3T3 cells and is down-regulated after treatment of Friend erythroleukemia
      cells with DMSO. Here we have reviewed: (i) the potential of nuclear PLC beta 1
      to be a target for anti-cancer drug, (ii) the capability of this PLC isoform,
      when activated by IGF-I, to be a key signalling molecule in the onset of DNA
      synthesis, via DAG generation and PKC alpha translocation to the nucleus, (iii)
      the chromosome mapping of PLC beta 1 gene. The differentiation program of Friend
      cells can be activated by other agents besides DMSO including tiazofurin, an anti
      tumor drug, also capable of affecting the nuclear inositol lipid cycle.
      Tiazofurin induces a lowering of the activity of PLC beta 1 due to down
      regulation of this isoform as revealed by both Western blotting and Northern
      blotting analyses. Using Swiss 3T3 cells stably transformed with an antisense PLC
      beta 1 construct, the knock-out of the PLC beta 1 gene induces both a loss of PLC
      beta 1 expression, as determined by Western blots, and a loss of the mitogenic
      responsiveness to IGF-I. These events show a direct relationship between nuclear
      PLC beta 1 evoked signals and IGF-I induced cell proliferation. Finally, the
      assignment of the PLC beta 1 gene to the band q35-36 of rat chromosome 3 paves
      the way for further genetic studies given the fact that the region where PLC beta
      1 gene maps is a hot spot for genetic alterations in a number of experimentally
      induced rat tumors. Taken as a whole, these results assign a key role to the
      regulation of nuclear PLC activity and expression both in growth-factor activated
      mitogenesis and in in vitro erythroid differentiation.

PMID- 8869744
TI  - The phosphatidylinositol 4-phosphate 5-kinase family.
AB  - The existence of a PIP5K family of enzymes has been suggested by Western blotting
      and purification of numerous PIP5Ks from various tissues and cell types. The
      erythrocyte has at least two PIP5Ks, named PIP5KI and PIP5KII, while the brain
      appears to have even more isoforms. The cloning of the first PIP5K, the PIP5KII
      alpha, is just the beginning of the molecular classification of this protein
      family. The PIP5KII alpha sequence has shown that these enzymes lack obvious
      homology to protein, sugar and other lipid kinases. The identification of two S.
      cerevisiae homologues, Mss4p and Fab1p, confirms that this family of kinases is
      widely distributed in eukaryotes. Not surprisingly, cloning experiments have
      identified additional isoforms. By cloning additional isoforms, insights into the
      structure and functions of this family of enzymes will be gained. One reason for
      a large family of PIP5Ks is that many forms of regulation and cellular functions
      have been ascribed to PIP5Ks, as summarized in Figure 10. Some of these
      functional links result from PtdIns[4,5]P2 being required for a given process,
      but the direct involvement of specific PIP5Ks is not well defined. Which PIP5K
      isoforms are regulated by a specific mechanism or are involved in a cellular
      process often is not clear. For example, which PIP5Ks produce PtdIns[4,5]P2 that
      is hydrolyzed by PLC or phosphorylated by the PI 3-kinase is not known. A few
      exceptions are PIP5KII not being able to phosphorylate PtdIns[4,5]P2 in native
      membranes, and PIP5KIs being stimulated by PtdA, required for secretion, and
      possibly regulated by G proteins of the Rho subfamily. The multiplicity of
      regulation and functions of each PIP5K isoform remains to be elucidated. Another
      factor governing the number of isoforms may be presence of multiple pools of
      polyphosphoinositides and the localizing of PIP5K function within cells. The
      polyphosphoinositides appear to be compartmentalized within cells and each pool
      appears to be sensitive to specific signals. These polyphosphoinositide pools may
      include those in the plasma membrane that are used by PLC, nuclear pools that
      appear to turn over separately from cytoplasmic pools and a small pool at sites
      of vesicle fusion with the plasma membrane. Each pool may be controlled by a
      specific PIP5K isoform. This would explain the diversity of PIP5K cellular roles.
      Another possibility is that the PIP5Ks are localized to certain areas of the cell
      by being part of a protein or proteolipid complex. Furthermore, the presence of
      PITP or PLC in the complex would potentially impart specificity and speed on the
      use of PtdIns[4]P and PtdIns[4,5]P2 because these lipids could be channeled
      quickly from one enzyme to the next. The concept of localized complexes
      containing particular PIP5K isoforms that control the composition of different
      polyphosphoinositide pools will likely be important as the family of PIP5K
      isoforms grows.

PMID- 8869745
TI  - The role of thymidylate synthase in cellular regulation.
AB  - Thymidylate synthase plays a central role in the biosynthesis of thymidylate, an
      essential precursor for DNA biosynthesis. In addition to its role in catalysis
      and cellular metabolism, studies from our laboratory have shown that thymidylate
      synthase functions as an RNA binding protein. Specifically, thymidylate synthase
      binds with high affinity to its own mRNA resulting in translational repression.
      An extensive series of experiments have now been performed to elucidate the
      molecular elements underlying the interaction between thymidylate synthase and
      its own mRNA. These studies have shed new light into the critical nucleotide
      sequences and/or secondary structure that are important for protein recognition.
      As well, studies to define the domains on the protein essential for RNA binding
      are currently underway. In addition to the characterization of the cis- and trans
      acting elements underlying the interaction between thymidylate synthase and its
      own mRNA, we have recently shown that thymidylate synthase has the capacity to
      specifically bind in vitro and in vivo to other cellular RNA species. In this
      regard, thymidylate synthase interacts with the mRNAs of the c-myc onocogene and
      the p53 tumor suppressor gene. These two genes have been shown to play critical
      roles in cell cycle control, DNA biosynthesis, and apoptosis. In vitro studies
      reveal that the interaction of TS with these cell-cycle related mRNAs results in
      their translational repression. While the biological significance of these
      cellular RNA/TS protein interactions remains to be defined, these studies suggest
      a potential role for TS as a mediator in the coordinate regulation of several
      critical aspects of cellular metabolism.

PMID- 8869746
TI  - rTS gene expression is associated with altered cell sensitivity to thymidylate
      synthase inhibitors.
AB  - rTS is a recently discovered gene, phylogenetically conserved and found to be
      expressed in a wide variety of cell lines. rTS has also been found to be
      overexpressed in two cell lines resistant to FU and to MTX. The MTX-resistant
      cell line was found to have a high degree of cross resistance to several TS
      inhibitors. An apparent paradox to this correlation of rTS overexpression and
      resistance to TS inhibitors is the observation that expression of transfected rTS
      alpha results in enhanced sensitivity of cells to the TS inhibitor prodrug TFT
      and a modest increase in resistance to FUdR. Since immunoprecipitation of TS
      leads to the co-immunoprecipitation of two proteins within the expected molecular
      weight range of the two rTS proteins, it may be that both proteins bind to TS in
      vivo and modify its activity. Preliminary data substantiate this conclusion. It
      is conceivable that the ratio of the two rTS proteins associated with TS in vivo
      may differentially alter TS activity depending upon their stoichiometry or
      possibly posttranslational modification. Thus it may be possible for rTS to
      confer greater sensitivity to one pyrimidine analog (e.g., TFT) which is a
      product analog but to increase resistance or have a minor effect on a substrate
      analog (e.g., FdUMP) by stabilizing different conformations of TS. The structure
      of the rTS proteins suggests they are expected to have catalytic activity which
      involves proton abstraction from an alpha-carbon of a carboxyl group. Whether
      this enzyme activity is functional and related to pyrimidine metabolism awaits
      further study.

PMID- 8869748
TI  - Regulation of lipogenic enzyme expression by glucose in liver and adipose tissue:
      a review of the potential cellular and molecular mechanisms.
AB  - Regulation of gene expression by nutrients is an important part of the mechanisms
      allowing mammals to adapt to their nutritional environment. This is especially
      true for enzymes involved in the storage of energy such as the lipogenic and
      glycolytic enzymes in the liver and adipose tissue. We review in the present
      paper the cellular and molecular mechanisms involved in the regulation of
      glycolytic and lipogenic enzyme gene expression by glucose. In vivo and in vitro
      experiments have demonstrated that FAS and ACC gene expression is upregulated by
      glucose in adipose tissue, FAS, ACC and L-PK expression in the liver and ACC and
      L-PK expression in a pancreatic beta-cell line. This regulation involves the
      stimulation of their transcription. In order for glucose to act as a gene
      inducer, it must be metabolized. In adipose tissue, insulin increases indirectly
      the expression of FAS and ACC by stimulating glucose metabolism through its well
      known effect on glucose transport. In the liver, the action of insulin is also
      indirect by allowing the expression of glucokinase and hence by increasing
      glucose metabolism. In the liver, fructose has a potentiating effect on the
      stimulation of gene expression by glucose through its stimulatory effect on
      glucokinase activity. Several evidences suggest that glucose-6-phosphate is the
      signal metabolite: (i) the effect of glucose is mimicked by 2-deoxyglucose (a
      glucose analogue whose metabolism stops after its phosphorylation by hexokinase)
      in adipose tissue and beta-cell line but not in the liver in which 2-deoxyglucose
      6-phosphate does not accumulate, (ii) intracellular glucose-6-phosphate
      concentration varies in parallel with ACC, FAS and L-PK mRNA concentrations in
      liver, adipose tissue and beta-cell line, (iii) in vivo, the kinetics of hexose
      phosphate fits with the time-related pattern of gene induction. Glucose response
      elements have been characterized on three genes, L-PK, S14 (a gene which codes
      for a protein of unknown function but which is directly related to lipogenesis)
      and FAS. These glucose response elements have all in common the presence of a
      sequence 5'-CACGTG-3' which binds a transcription factor of the basic domain,
      helix-loop-helix, leucine zipper family called USF/MLTF, although the
      organization of the overall glucose response element probably differs from one
      gene to another. The mechanisms linking glucose-6-phosphate to the glucose
      responsive transcription complex are presently largely unknown.

PMID- 8869747
TI  - The hormonal regulation of pyruvate dehydrogenase complex.
AB  - The pyruvate dehydrogenase complex has a central role in the regulation of
      mammalian metabolism as it represents the point-of-no-return in the utilization
      of carbohydrate. This article summarizes our studies into how signalling systems
      initiated by hormones binding to cell surface receptors can reach the pyruvate
      dehydrogenase system which is located within the inner mitochondrial membrane.
      One class of hormones which activate pyruvate dehydrogenase are those that
      increase cytoplasmic Ca2+. A wide range of studies on isolated enzymes, separated
      mitochondria and intact cell preparations have shown that the activation is due
      to the stimulation of pyruvate dehydrogenase phosphatase. Two other
      intramitochondrial dehydrogenases which regulate the citrate acid cycle are
      activated in parallel and this is an important means of balancing the supply of
      ATP to increasing cell demand. Insulin is also able to activate pyruvate
      dehydrogenase, but this is restricted to fat and other cells capable of
      lipogenesis. Insulin acts by stimulating pyruvate dehydrogenase phosphatase, but
      the activation does not involve alterations in Ca2+. The signalling pathway
      involved has not been established, but it appears to be quite distinct from those
      involved in many other actions of insulin.

PMID- 8869749
TI  - A novel action of lithium: stimulation of glutamate release and inositol 1,4,5
      trisphosphate accumulation via activation of the N-methyl D-aspartate receptor in
      monkey and mouse cerebral cortex slices.
AB  - Beginning at therapeutic concentrations (1-1.5mM), the anti-manic-depressive
      drug, lithium, stimulated the release of the major excitatory central
      neurotransmitter, glutamate, in monkey cerebral cortex slices in a time- and
      concentration-dependent manner, and this was associated with increased inositol
      1,4,5-trisphosphate [Ins(1,4,5)P3] accumulation. (+/-)-3-(2-Carboxypiperazin-4
      yl)-propyl-1-phosphoric acid (CPP), dizocilpine (MK-801), ketamine, and Mg(2+)
      antagonists to the N-methyl D-aspartate (NMDA) receptor/channel complex
      selectivity inhibited lithium-stimulated Ins(1,4,5)P3 accumulation. Antagonists
      to cholinergic-muscarinic, alpha 1-adrenergic, 5-HT2-serotoninergic and H1
      histaminergic receptors had no effect. Antagonists to non-NMDA glutamate
      receptors had no effect on lithium-stimulated Ins(1,4,5)P3 accumulation. Possible
      reasons for this are discussed. Similar results were obtained in mouse cerebral
      cortex slices. Carbetapentane, which inhibits glutamate release, inhibited
      lithium-induced Ins(1,4,5)P3 accumulation in this model. It is concluded that the
      primary effect of lithium in the cerebral cortex slice model is stimulation of
      glutamate release, which, via activation of the NMDA receptor, leads to Ca2+
      entry. Ca2+ entry, in turn, activates phospholipase C. These effects may have
      relevance to the therapeutic action of lithium in the treatment of manic
      depression, as well as its toxic effects, especially at lithium blood levels
      above 1.5mM. A general conclusion which can be drawn from these studies and
      earlier studies in our laboratory is that lithium potentiates the action of
      phospholipase C, whether this enzyme is activated by lithium-induced presynaptic
      release of neurotransmitter, such as glutamate, or by the addition of an
      exogenous neurotransmitter, such as acetylcholine. However, this does not appear
      to be due to a direct activation of phospholipase C.

PMID- 8869751
TI  - Inhibition of experimental metastasis by enzyme inhibitors from microorganisms
      and plants.
AB  - Various antibacterial compounds, antitumor compounds, enzyme inhibitors and
      recent signal transduction inhibitors have been discovered from microorganisms
      and plants. Therefore, it should be possible to find antimetastatic compounds
      from these sources, if a simple assay system is available. We isolated several
      enzyme inhibitors from nature to inhibit experimental metastasis. Leupeptin is an
      old protease inhibitor and inhibited blood-borne lung metastasis of hepatoma
      cells in rats. A leupeptin analogue inhibiting urokinase inhibited in vitro
      invasion of human fibrosarcoma cells. Alpha-glucosidase inhibitors such as epi
      CPL and baicalein inhibited in vitro invasion and in vivo metastasis of mouse
      melanoma cells. A mannosidase inhibitor, mannostatin A, also inhibited in vitro
      invasion of mouse melanoma cells. Oncogene function inhibitors induce normal
      phenotypes in the oncogene-expressing cells. As expected, they inhibited tumor
      cell invasion in vitro.

PMID- 8869750
TI  - Phosphoinositide signalling in human neuroblastoma cells: biphasic effect of Li+
      on the level of the inositolphosphate second messengers.
AB  - Lithium has a biphasic effect of the agonist-dependent accumulation of
      Ins(1,4,5)P3 in human neuroblastoma SH-SY5Y cells. These effects consist of a
      transient reduction, followed by a long-lasting increase in Ins(1,4,5)P3 as
      compared to controls. The Li+ effects are dose dependent, and were observed at
      concentrations used in the treatment of bipolar disorders, and thus may have
      therapeutic implications. The mechanism of the Li+ effect on Ins(1,4,5)P3
      accumulation requires further investigation. The transient reduction of
      Ins(1,4,5)P3 was observed under conditions where Li+ causes only a moderate
      increase in the inositol mono- and bi-phosphates. Supplementation with exogenous
      inositol had no effect on the level of Ins(1,4,5)P3, indicating that the
      mechanism of the Li(+)-dependent reduction of Ins(1,4,5)P3 is not due to inositol
      depletion. Li+ did not interfere with degradation of Ins(1,4,5)P3 after receptor
      blockage with atropine, suggesting that Li+ has no direct effect on the
      Ins(1,4,5)P3 metabolizing enzymes. A direct effect of Li+ on the phospholipase C
      is also unlikely. Entry of Ca2+ into the cells is an important factor, which
      affects agonist-stimulated accumulation of Ins(1,4,5)P3, as well as absolute
      values of Li(+)-dependent increase in Ins(1,4,5)P3; however, it is not essential
      for the manifestation of Li+ effects. Our results also show that manifestation of
      Li+ effects in human neuroblastoma cells requires the stimulation of muscarinic
      receptors and activation of PLCs, PKCs, and/or that other staurosporine/H-7/GF
      109203X-sensitive protein kinases are involved in the regulation of Ins(1,4,5)P3
      during the plateau phase of ACh-stimulation. We also suggest an important role
      for these enzymes in the Li(+)-dependent elevation of Ins(1,4,5)P3.

PMID- 8869752
TI  - The retinoblastoma gene product is a negative modulator of the apoptotic pathway.

PMID- 8869753
TI  - The role of proteolytic enzymes in the deposition of amyloid proteins.
AB  - Serum albumin from normal individuals and short-term hemodialysis patients was
      separated by isoelectric focusing into two bands with pIs of 4.7 (Alb-I) and 4.2
      (Alb-II). However, serum albumin from long-term hemodialysis patients with CTS
      migrated as a single band with a pI of 4.2 (Alb-II). The major constituent of the
      100,000 x g supernatant proteins from amyloid tissues that were collected from
      hemodialysis patients with CTS was Alb-II. Incubation of serum albumin by
      lysosomal enzymes in vitro caused the modification of Alb-I to Alb-II. The ratio
      of Alb-I/Alb-II was changed in vivo during the hemodialysis and in in-vitro
      experiments designed to circulate the sera. Lysosomal enzyme levels such as acid
      phosphatase, glucosidase, glucuronidase and dipeptidyl aminopeptidase in the
      serum of hemodialysis patients were higher than those of normal individuals.
      Plasma levels of acid phosphatase and cathepsin L were elevated during
      hemodialysis. These results suggest that the conformational change of serum
      albumin by proteolytic modification during hemodialysis may be involved in the
      hemodialysis-associated amyloidosis.

PMID- 8869754
TI  - Cellular proteases involved in the pathogenicity of enveloped animal viruses,
      human immunodeficiency virus, influenza virus A and Sendai virus.
AB  - In enveloped viruses, post-translational proteolytic activation is a critical
      step for the fusion activity and thus for the infectivity of the virus. In
      addition to the membrane receptors for the viruses, proteolytic activation is
      indispensable for effective virus spread in the infected host and it is a prime
      determinant for pathogenicity. Here we described the host cellular processing
      proteases, tryptase Clara and tryptase TL2, which proteolytically activate the
      infectivity of influenza A and Sendai viruses in the respiratory tract and HIV-1
      in human CD4+ T cells, respectively. A novel trypsin-like protease, designated
      tryptase Clara, was purified from rat lung. The enzyme is localized in Clara
      cells of the bronchial epithelium and is secreted into the airway lumen. The
      enzyme specifically recognizes the consensus cleavage motif Gln(Glu)-X-Arg of
      influenza A and Sendai viruses and proteolytically activates the envelope fusion
      glycoproteins of the progeny viruses extracellularly in the airway lumen. Human
      mucus protease inhibitor and pulmonary surfactant in airway fluid inhibited the
      proteolytic activation of these viruses and also suppressed multiple cycles of
      viral replication in vitro. These results suggest that an imbalance between the
      amount of tryptase Clara and that of endogenous inhibitors in airway fluid is a
      prime determinant for pneumopathogenicity of the viruses. Therefore supplementing
      an endogenous inhibitor at therapeutic doses may protect against virus infection.
      In HIV-1 infection, binding of the gp120 envelope glycoprotein to the CD4
      receptor is not sufficient in itself to allow virus entry, and an additional
      component(s) in the membrane is required for cell infection as a cofactor. We
      isolated a serine protease named tryptase TL2, in the membrane of CD4+
      lymphocytes, which specifically binds to the V3 loop of HIV-1 gp120 as a
      cofactor. After binding, tryptase TL2 proteolytically processed gp120 into two
      protein species of 70 and 50 kDa and the cleavage was suppressed by a
      neutralizing antibody against the V3 loop. The amino acids that constitute the
      cleavage sites in the V3 loop of almost all HIV isolates are variable, but they
      are restricted to those which are susceptible to chymotryptic and/or tryptic
      enzyme. The multi-substrate specificity of tryptase TL2, which has tryptic and
      chymotryptic specificities, may correspond tot he variability of the V3 loop. The
      selective cleavage of the V3 loop by tryptase TL2 may lead to a conformational
      change of gp120, resulting in the dissociation of gp120 from gp41, exposing the
      fusogenic domain of the transmembrane protein gp41 following virus-host cell
      fusion.

PMID- 8869755
TI  - Influence of bile salts on hepatic mdr2 P-glycoprotein expression.
AB  - Mdr2 P-glycoprotein is expressed in the canalicular membrane of the mouse
      hepatocyte and is responsible for phospholipid secretion into bile. It is our
      hypothesis that it functions as a flippase in the translocation of
      phosphatidylcholine from the inner leaflet to the outer leaflet of the
      canalicular membrane. We have investigated the influence of different types of
      bile salts on the expression levels of mdr2 Pgp. Feeding mice a cholate
      supplemented diet results in an increased mdr2 mRNA level, and this is
      accompanied by an increased biliary phospholipid secretion capacity. Cholate is a
      more hydrophobic bile salt than the main endogenous bile salt, muricholate. The
      induction of mdr2 gene expression and concomitant increase in phospholipid
      secretion are in line with the function of biliary phospholipids to inactivate
      the detergent action of hydrophobic bile salts.

PMID- 8869756
TI  - The role of dietary folate in modulation of folate receptor expression,
      folylpolyglutamate synthetase activity and the efficacy and toxicity of
      lometrexol.
AB  - We have studied the molecular effects of a LFD in a murine model in order to
      better define the biochemical changes associated with folate deficiency. In
      addition, we have demonstrated the effect of a LFD on the pharmacokinetic profile
      and therapeutic activity and toxicity of lometrexol. These studies showed
      increased density of FR in tumors implanted in LFD mice and a decrease in the
      affinity of these receptors for folic acid. The results suggest that tumors can
      compensate for low folate bioavailability by up-regulation of a second FR with
      slightly lower affinity for folic acid. The higher density of this FR would
      provide greater capacity for garnering serum folate. FPGS activity increased in
      several tumors and liver and kidney of LFD mice. The increase in this enzyme
      activity would result in enhanced polyglutamation of folates and classical
      antifolates and thus increased cellular retention. Consistent with these changes
      in liver FPGS, mice injected i.v. with a single dose of lometrexol accumulated
      significantly more drug in liver and tumors of LFD animals compared to SD mice.
      Also, higher liver concentrations of lometrexol persisted longer in LFD mice.
      Polyglutamate analysis showed that longer polyglutamate forms appeared earlier in
      liver of LFD mice. After 7 days, longer polyglutamyl forms were recovered from
      liver of LFD mice (octa- and hepta-glutamyl lometrexol) compared to those on SD.
      A comparison of the efficacy and toxicity of lometrexol in C3H mammary tumor
      bearing mice showed that in mice on LFD, lometrexol treatment produced a delayed
      toxicity with an LD50 of 0.1-0.3 mg/kg, a 3000-fold increase in lethality
      compared to SD mice. Supplementation of mice with folic acid restored anti-tumor
      activity and increased the therapeutic dose-range over which efficacy could be
      assessed. These studies support the use of folic acid supplementation for cancer
      patients treated with antifolate therapy in order to prevent the biochemical
      changes in FR and FPGS associated with folate deficiency, prevent delayed
      toxicity to GARFT inhibitors and enhance the therapeutic potential of this class
      of drugs.

PMID- 8869757
TI  - Cellular signalling as a target in cancer chemotherapy. Phospholipid analogues as
      inhibitors of mitogenic signal transduction.
AB  - Mitogenic signalling mechanisms emerged as novel targets for tumor chemotherapy.
      Current strategies for pharmacological interventions are briefly discussed.
      Phospholipid analogues are treated in greater detail. It is shown here that this
      new class of antitumor agents acts as inhibitors of mitogenic signal
      transduction. The common target of all phospholipid analogues studied so far is
      the phosphatidylinositol (PI)-specific phospholipase C (PLC). This results in an
      attenuated formation of inositol-1,4,5-trisphosphate (IP3) and diacylglycerol
      (DAG). The reduction in IP3-levels leads to a depressed release of Ca2+ from
      internal stores, and the reduced formation of DAG interferes with the growth
      factor-induced activation of protein-kinase C (PKC). In addition to the effect on
      PI-specific PLC, most phospholipid analogues inhibit PKC directly by interacting
      with the regulatory domain of the enzyme. This effect, however, is not observed
      with all phospholipid analogues. Some potent growth inhibitory representatives
      from this group like hexadecylphosphoserine or hexadecylphosphonoserine do not
      affect PKC in cell-free extracts. It is concluded, therefore, that the direct
      inhibition of PKC is not required for the growth-inhibitory activity of these
      agents. The ability of phospholipid analogues to interact with PKC was also not
      found to be correlated the occurrence of unwanted side effects. Phospholipid
      analogues have also been found to act as inhibitors of phospholipase D (PLD).
      However, in this case the correlation to the growth inhibitory potency of various
      phospholipid analogues was less clear, so that the contribution of the PLD
      inhibition to the growth inhibitory effect of these agents still remains to be
      established. The inhibition of the thrombin-induced rise in cytosolic free Ca2+
      by phospholipid analogues is reversible by washing the cells in phospholipid-free
      medium. These findings suggest that phospholipid analogues do not cause
      persistent membrane damage and may act as cytostatic rather than cytotoxic
      agents.

PMID- 8869758
TI  - CGRP: blood flow and more?

PMID- 8869759
TI  - Distribution of [3H]-sumatriptan binding sites in human brain.

PMID- 8869760
TI  - Are the International Headache Society criteria for headache useful?

PMID- 8869761
TI  - The International Headache Society classification and diagnostic criteria are
      valid and extremely useful.

PMID- 8869763
TI  - Differential sensitivity to morphine challenge in migraine sufferers and headache
      exempt subjects.
AB  - The effectiveness of a therapeutic dose of morphine in relieving migraine attacks
      was compared with placebo. Morphine was no more effective than placebo and
      provoked severe side effects. When low-dose morphine was administered to normal
      non-headache controls and migraineurs when headache-free, physical and
      psychologic reactions were induced only in migraineurs. On pupillometric study,
      only migraineurs had defective morphine-miosis. It is suggested that the observed
      clinical phenomena in response to morphine can be explained by differences in
      expression and sensitivity of some opioid receptor subtypes in migraine.

PMID- 8869764
TI  - Migraine without aura and migraine with aura are inherited disorders.
AB  - The familial occurrence and mode of inheritance were analysed in families with
      migraine without aura (MO) and migraine with aura (MA). The probands were found
      among 4000 persons from the general population. All persons with MA were included
      as probands, and an equivalent number of probands with MO was selected as a
      random sample among those with MO. Spouses and first-degree relatives were
      blindly interviewed. All interviews were performed by one neurological research
      fellow. The distinct familial patterns indicate that MO and MA have a different
      aetiology. Compared with the general population, the first-degree relatives of
      probands with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold
      increased risk of MO, indicating that both genetic and environmental factors are
      important in MO. The first-degree relatives of probands with MA had a four-fold
      increased risk of MA while spouses had no increased risk of MA, indicating that
      MA is determined largely by genetic factors. The complex segregation analysis
      indicated that both MO and MA have multifactorial inheritance without
      generational difference.

PMID- 8869765
TI  - Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres
      and induces vasodilatation of human cerebral arteries concomitant with activation
      of adenylyl cyclase.
AB  - The vasomotor effects of calcitonin gene-related peptide (CGRP) analogues have
      been studied in circular segments of fresh human cerebral arteries obtained at
      neurosurgical operations using a sensitive in vitro system. Human alpha-CGRP,
      human beta-CGRP, rat alpha-CGRP and rat beta-CGRP induced strong and potent
      relaxation of precontracted circular vessel segments. The Imax (maximum relaxant
      effect) to human calcitonin was low and the pD2 (concentration for half maximum
      effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human alpha
      CGRP8-37 blocked the response to human alpha-CGRP but not to human beta-CGRP,
      while the putative antagonist [Tyr]CGRP28-37 did not. Capsaicin (10(-15)-10(-8)M)
      caused relaxation of the cerebral arteries by 22% of precontraction. Pre
      treatment with 10(-6)M human alpha-CGRP8-37 inhibited this relaxation. Human
      alpha-CGRP increased the cyclic AMP content of human cerebral arteries in a
      concentration-dependent manner. This increase in adenylyl cyclase activity was
      blocked by human alpha-CGRP8-37. The results suggest that CGRP-1 receptors
      coupled to adenylyl cyclase are present in human cerebral arteries.

PMID- 8869766
TI  - Autoradiographic distribution of [3H]sumatriptan-binding sites in post-mortem
      human brain.
AB  - The anatomical distribution of [3H]sumatriptan-binding sites was analysed in
      brain tissue sections from 11 subjects. Relevant concentrations of
      [3H]sumatriptan-binding sites were seen in areas such as visual cortex > locus
      niger > globus pallidus > layers IV-V of the frontal cortex > subiculum >
      entorhinal cortex > nucleus tractus solitarius > nucleus trigeminalis caudalis.
      This distribution of [3H]sumatriptan-binding sites in the human brain shows some
      differences when compared with that of 5HT1D receptors, confirming that, besides
      5HT1D, sumatriptan also binds to 5HT1F receptor subtype. Some species differences
      are evident between the distribution of [3H]sumatriptan-binding sites in the
      human brain and that reported for guinea-pig and rat brains, emphasizing that
      caution is needed in extrapolating experimental data from animals to humans.
      Furthermore, these data help to explain some of the therapeutic actions of
      sumatriptan. The remarkable levels of binding found in areas as nucleus tractus
      solitarius and nucleus trigeminalis caudalis suggest that in migraine attacks
      sumatriptan could exert its specific anti-emetic effects and, partly at least,
      induce analgesia by directly acting over these brain nuclei.

PMID- 8869767
TI  - Serotonin syndrome complicating migraine pharmacotherapy.
AB  - Serotonin syndrome, a condition with numerous clinical neurological
      manifestations, is the result of central serotonergic hyperstimulation. Features
      of the syndrome include mental status and behavioral changes (agitation,
      excitement, hypomania, obtundation), motor system involvement (myoclonus,
      hemiballismus, tremor, hyperreflexia, motor weakness, dysarthria, ataxia) and
      autonomic symptoms (fever, chills, diarrhea). Serotonin syndrome has been
      reported exclusively in patients on medications for psychiatric illness and
      Parkinsonism, despite the fact that the putative action of many antimigraine
      agents also involves the serotonin system. We herein report six patients with
      migraine who developed symptoms suggestive of the serotonin syndrome. Five were
      taking one or more serotomimetic agents for migraine prophylaxis (sertraline,
      paroxetine, lithium, imipramine, amitriptyline). In each case the symptoms and
      signs developed in close temporal proximity with use of a migraine abortive agent
      known to interact with serotonin receptors. In three instances the agent was
      subcutaneous sumatriptan and, in three, intravenous dihydroergotamine. In each
      instance the symptoms were transient and there was full recovery. With the ever
      increasing use of migraine medications active at serotonin receptor sites, cases
      of serotonin syndrome will likely occur more frequently. It is important that
      physicians treating migraine are aware of the serotonin syndrome and are able to
      recognize its varying presentations.

PMID- 8869768
TI  - Post-marketing cohort study comparing the safety and efficacy of flunarizine and
      propranolol in the prophylaxis of migraine.
AB  - A comparative post-marketing surveillance study of the safety and efficacy of
      flunarizine and propranolol in the treatment of migraine was carried out. General
      practitioners in Belgium and the Netherlands each recruited patients for whom
      they would prescribe one of the study medications in the normal course of their
      treatment and recorded all medical events on follow-up forms for up to 8 months.
      A total of 1601 migraine patients were enrolled; 838 in the flunarizine cohort
      and 763 in the propranolol cohort. Propranolol was somewhat better than
      flunarizine in reducing the severity of migraine attacks, although this may have
      been due to a selection bias. Discontinuations of therapy due to events
      considered likely to be treatment-related were mostly due to the recognized side
      effects of the two drugs. As regards the occurrence of depressions, a total of 58
      patients had depressive events, 34 in the flunarizine cohort and 24 in the
      propranolol cohort. Whereas migraine itself appears to be associated with an
      increased risk of depression, the number of previous migraine treatments was
      shown to be an additional risk factor for the development of depression in
      patients receiving flunarizine as was a history of depression. Overall, there was
      no appreciable difference in the risk/benefit ratio between flunarizine and
      propranolol.

PMID- 8869769
TI  - Long-term follow-up after flunarizine or nimodipine discontinuation in migraine
      patients.
AB  - Various open and controlled studies have confirmed the antimigraine action of
      flunarizine, while the antimigraine properties of nimodipine are still open to
      controversy. Moreover, only a few studies include an additional follow-up after
      discontinuation of migraine prophylaxis with either drug. We carried out a single
      blind evaluation of the efficacy and tolerance of flunarizine (25 patients) in
      comparison with nimodipine (25 patients) and the long-term effect after
      discontinuation of a 6-month treatment. Both medications significantly reduced
      migraine frequently and severity. Flunarizine was more efficacious than
      nimodipine in reducing migraine frequency (p < 0.001), pain severity (p < 0.05),
      migraine index (p < 0.05) and corrected migraine index (p < 0.05). The positive
      effect lasted 8.4 +/- 4.0 months after discontinuation of flunarizine and 4.9 +/-
      3.5 months after nimodipine (p < 0.05). Our results suggest that flunarizine is
      more effective than nimodipine in the prophylactic treatment of migraine. The
      positive effect after drug discontinuation lasts longer with flunarizine,
      compared to nimodipine.

PMID- 8869770
TI  - Recurrent paroxysmal headache associated with facial ecchymosis.
AB  - The case of a 58-year-old man with chronic paroxysmal headache and facial
      ecchymosis is described. The headache was pulsating, of short duration, without
      nausea or vomiting, and occasionally associated with flashing lights. Ecchymoses
      were mainly located in the middle forehead region and their appearance was
      associated with a reduction in intensity of the headache. Blood coagulation tests
      were within normal limits, and a skin biopsy of the ecchymotic lesion ruled out
      an underlying vasculitis. These attacks were difficult to include in any
      particular type of headache, although some aspects were similar to migraine
      headache. The possible mechanism of hemorrhages is discussed.

PMID- 8869771
TI  - Message from the new president of the ISPN.

PMID- 8869772
TI  - Synostectomy versus complex cranioplasty for the treatment of sagittal
      synostosis.
AB  - Although pediatric neurosurgeons traditionally have been trained to perform a
      sagittal synostectomy for the treatment of sagittal synostosis, numerous articles
      advocating modifications of this procedure or more complex cranial vault
      reconstructions point our the inadequacies of strip craniectomy in providing
      optimal short- and long-term cosmesis. This review addresses the major arguments
      for and against performing complex cranioplasties for sagittal synostosis, as
      well as issues regarding timing of surgery, mortality and morbidity, increased
      need for blood transfusion, and increased expense. The authors support the
      contention that for the majority of infants with sagittal synostosis, complex
      calvarial vault reconstruction provides a better outcome with little increase in
      operative risk.

PMID- 8869773
TI  - Hemispherectomy for intractable seizures in children: a report of 58 cases.
AB  - Fifty-eight children who underwent anatomical, functional, or modified anatomical
      hemispherectomy for intractable seizures from 1986 to 1995 were evaluated for
      seizure control, motor function, and complications. Age at surgery ranged from
      0.3 to 17.3 years (median 2.8 years). Twenty-seven anatomical, 27 functional, and
      4 modified anatomical hemispherectomies were performed. Seizure control and motor
      function in the 50 patients with more than 1 year follow-up revealed a 90% or
      better reduction in seizure frequency in 44/50 (88%) overall: 19/22 (86%)
      anatomical, 23/26 (89%) functional, and 2/2 modified anatomical. Motor function
      of the preoperatively hemiparetic extremities was improved or unchanged
      postoperatively in 38/50 (76%) of the patients. Complications included one
      intraoperative death, one late death from shunt obstruction managed elsewhere,
      late postoperative seizure breakthrough requiring reoperation and further
      disconnection in 5/27 functional hemispherectomy patients, mild cerebrospinal
      fluid infections in 3/27 anatomical hemispherectomy patients, and hydrocephalus
      requiring shunting in 3/27 functional hemispherectomy patients. A review of the
      literature and comparison of techniques is presented.

PMID- 8869774
TI  - Complications in paediatric craniopharyngioma treatment.
AB  - Forty-eight consecutive children treated for craniopharyngioma at the Juan P.
      Garrahan National Paediatric Hospital (Buenos Aires, Argentina) from 1988 to 1994
      are described. Complications of patients undergoing total resection alone and
      those undergoing subtotal or partial resection plus radiotherapy were compared.
      Survival time and quality of life proved more satisfactory in the former group,
      as there were no recurrences. In contrast, among the latter patients, 53%
      suffered relapses. Endocrinological complications were similar in the two groups.
      Postsurgical subdural haematomas were quite frequent and eight patients required
      treatment for intracranial hypertension. Vascular complications, though less
      common, led to high morbidity and mortality. There was a considerable incidence
      of shunt malfunction (80%), arguing against placement of a preoperative shunt,
      which tended besides to foster postsurgical subdural haematomas.

PMID- 8869775
TI  - Use of transcranial real-time ultrasonography for programming a shunt valve
      system.
AB  - For patients who suffer from hydrocephalus that is difficult to treat because of
      impaired intracranial compliance, a programmable shunt system may be a helpful
      alternative. However, especially during the first weeks after implantation, many
      radiological follow-up studies are necessary to achieve the optimum pressure
      level. The authors present the case of a 7-year-old boy who suffered from
      posthemorrhagic hydrocephalus and did not respond to conventional shunt valve
      systems. After implantation of a programmable shunt system, achieving the optimum
      craniospinal fluid (CSF) pressure level was difficult because the symptoms of
      over- and under-drainage were similar. Using transcranial real-time
      ultrasonography for evaluation of the diameter of the intracranial CSF spaces, we
      were able to adjust the correct pressure level without long-term intracranial
      pressure monitoring or daily computed tomography, which otherwise would have been
      necessary because of the ambiguous symptomatology. Transcranial real-time
      ultrasonography (TCUS) displays an image of the intracranial parenchyma and CSF
      spaces through the intact temporal bone and is a valuable, serially applicable
      bedside monitoring technique for patients requiring close imaging follow-up.

PMID- 8869776
TI  - A method of enlarging the opening of the third ventricular floor for flexible
      endoscopic third ventriculostomy.
AB  - In the Pediatric Neurosurgical Service of the Veterans General Hospital, Taipei,
      flexible endoscopic III ventriculostomy has been applied in children with
      noncommunicating hydrocephalus and periaqueductal/pineal tumor. We modified the
      technique to allow enlargement of the opening of the III ventricular floor. The
      use of an Atlas Wire Stone Extractor for this purpose is described.

PMID- 8869777
TI  - Leptomeningeal cyst in newborns due to vacuum extraction: report of two cases.
AB  - Two new cases of leptomeningeal cysts subsequent to vacuum extraction are
      reported. Both children presented with a huge, nonpulsating, transilluminating
      subgaleal collection over the anterior fontanel that appeared soon after
      instrument delivery. Plain X-rays, computed tomography, and magnetic resonance
      imaging confirmed that the subgaleal collection was cerebrospinal fluid and
      showed the presence of a diastatic coronal suture in both cases. Treatment
      consisted of duraplasty with periosteal flaps and application of fibrin glue. In
      one case, an associated porencephalic cyst was treated with a cystoperitoneal
      shunt. Surgical treatment of leptomeningeal cyst due to vacuum extraction is
      simple and should not be postponed, despite the tendency for the extracranial
      cyst to regress, because of the potential risk of continuous growth of an
      underlying porencephalic cyst and risk of neurological damage.

PMID- 8869778
TI  - Arteriovenous malformation associated with moyamoya disease.
AB  - The first case of a child with an arteriovenous malformation (AVM) associated
      with moyamoya disease is reported. The patient presented ischemic symptoms and
      underwent indirect bypass surgery on both sides when she was 5 years old. Four
      years later she suffered from headache, and a small AVM of the left frontal lobe
      associated with the moyamoya vessels was detected. Single photon emission
      computed tomography (SPECT) was performed at age 11 and demonstrated low local
      cerebral blood flow (CBF) in the left frontal lobe and right temporal lobe,
      although the revascularization after the bypass surgery seemed to be effective,
      as judged on pancerebral angiography. We feel that brain ischemia due to the
      moyamoya disease may have played a causative role in the development of the AVM.

PMID- 8869779
TI  - Congenital desmoid tumor of the scalp: a histologically benign lesion with
      aggressive clinical behavior.
AB  - Desmoid tumors are uncommon benign neoplasms of fibroblastic origin, frequently
      presenting in the abdomen or abdominal wall of adults. This tumor is well known
      to general surgeons and pathologists, but it has rarely been reported in the
      neurosurgical literature. We describe a neonate who presented with a right
      temporal subscalp tumor at birth. In spite of initial apparent total removal, the
      tumor recurred twice. We discuss the diagnostic pitfalls encountered in assessing
      this tumor and the difficulties in distinguishing, in the excised specimens,
      between desmoid and reactive fibrosis. We suggest that desmoid tumor should be
      considered in the differential diagnosis of scalp and calvarial masses in
      children. Complete excision is required to prevent recurrences, and sometimes a
      multidisciplinary team is needed to secure margin-free resection.

PMID- 8869780
TI  - Different neurologic outcomes in two patients with neonatal hyperinsulinemic
      hypoglycemia.
AB  - The authors report the cases of two patients with neonatal onset of hypoketotic
      hypoglycemia with hyperinsulinism and a poor response to diazoxide. Pancreatic
      venous sampling showed a diffuse pancreatic hyperplasia in one patient and a
      focal lesion in the other. The second patient, diagnosed after a significant
      delay, suffered severe long-term neurological sequelae, despite having more
      limited hyperplasia; the brain MRI also showed severe pathological changes in
      cortex and white matter, predominantly in the parieto-occipital region. Early and
      accurate diagnosis is critical in these patients in whom hypoglycemia is
      compounded by a lack of the ketone bodies which represent a vital alternative
      source of energy for the central nervous system.

PMID- 8869781
TI  - 24-year preoperative evolution of a temporal astrocytoma.
AB  - We report the case of a patient suffering since 5 months of age from complex
      focal seizures that could not be controlled with medication and who developed
      severe psychomotor retardation. When she was 25 years old she was operated on for
      a left temporal lobe type II astrocytoma which had been detected but
      misinterpreted on CT scans performed at 12 and 18 years of age. After surgical
      and radiotherapy treatment the patient was seizure-free for 9 months, but then
      epilepsy reappeared and the patient died 19 months after surgery. Postsurgical
      malignant transformation is suspected but not histologically confirmed.

PMID- 8869783
TI  - An expanded view of SIADH, hyponatremia and hypouricemia.

PMID- 8869782
TI  - CT, MRI, and PET in a case of intractable epilepsy.
AB  - We report the case of a child with drug-refractory partial epilepsy in whom
      computed tomography showed no abnormality and magnetic resonance imaging showed a
      noninvasive cystic lesion in the left hippocampus. The finding in the positron
      emission tomography study with L-[methyl-11C]-methionine as a tracer suggested a
      tumor. This finding was confirmed histologically.

PMID- 8869784
TI  - Increased dermal expression of ICAM-1 and VCAM-1 after administration of OKT3 in
      man.
AB  - OKT3 induces a systemic release of cytokines and a profound peripheral
      lymphocytopenia. In vitro, tumor necrosis factor-alpha, interleukin-1, and
      interferon-gamma increase adhesion molecule expression on vascular endothelium.
      To investigate the effects of OKT3 induced cytokine release on endothelial- and
      lymphocyte adhesion molecule expression in vivo, we studied sequential skin
      biopsies of six renal allograft recipients treated for acute rejection with 5 mg
      OKT3. An additional group of six patients treated for acute rejection with 50 mg
      methylprednisolone served as a control group. Compared to pre-treatment biopsies,
      biopsies taken 4.5- and 24 hours after the first OKT3 dose showed a maximal
      increase in VCAM-1 and ICAM-1 expression, respectively. In parallel, an increased
      number of CD2+, CD11a+, and CD49d+ mononuclear cells in the skin was observed in
      all OKT3 treated patients. No changes were observed after methylprednisolone
      treatment. We conclude that the OKT3 induced cytokine release induces increased
      ICAM-1- and VCAM-1 expression on vascular endothelium, leading to increased
      influx of CD2+ lymphocytes which may contribute to the peripheral lymphocytopenia
      after OKT3.

PMID- 8869786
TI  - DMSA renal scans in adults with acute pyelonephritis.
AB  - The 99mTc-DMSA scan is accepted as the most sensitive imaging modality for
      detecting areas of renal parenchymal scarring. More recently the DMSA scan has
      also been shown to be of value in imaging areas of renal parenchymal involvement
      in both children and adults with acute pyelonephritis. We assessed the acute DMSA
      scan findings in a consecutive series of 81 patients hospitalized with acute
      pyelonephritis. Acute pyelonephritis was diagnosed if the patient had a fever of
      > 37.8 degrees C, loin pain or tenderness and infected urine (99% Escherichia
      coli). Patients had a blood culture taken (8 positive), as well as a
      hematological (leukocytosis 75%) and biochemical screen, C-reactive protein (CRP)
      (increased in 57 of 66 [86%]) and urinary tract ultrasonography. If the initial
      DMSA scan was abnormal it was repeated after three months and in some instances
      again at six months. If persisting defects were noted an intravenous urogram was
      then undertaken. Of the 81 patients, 37 (46%) had an abnormality on the DMSA
      scan. Nineteen had a single defect, 12 multifocal defects, five features
      suggestive of pre-existing renal parenchymal scarring (all later shown to have
      reflux nephropathy) and one a shrunken kidney. Those patients with an abnormal
      scan had a higher CRP concentration than those with a normal scan. Of the 31
      patients who had either a focal or multifocal defect on their initial DMSA scan
      there was adequate follow-up on 24 patients. In 18 of these the defects had
      resolved by six months (usually within three months), while of the remainder,
      three were shown to have reflux nephropathy, one had a large single renal cyst
      and another an area of parenchymal calcification. Fifty-three of 76 patients
      (70%) had normal ultrasonography. In adults with acute pyelonephritis, the DMSA
      scan may prove to be the most useful renal imaging procedure.

PMID- 8869785
TI  - Risk factors for nephropathy and cardiovascular disease in diabetic Northern
      Minnesota American Indians.
AB  - Although complications of diabetes are common among Southwest American Indians,
      little is known about diabetes and associated risk factors for nephropathy and
      cardiovascular disease in other genetically distinct tribes. We conducted a
      retrospective analysis of 665 diabetic patients at two Chippewa Indian
      reservations in northern Minnesota to evaluate the prevalence of risk factors for
      diabetic nephropathy and cardiovascular disease. In 79 patients, a more detailed
      study was carried out, including an assessment of renal function and urinary
      albumin excretion (UAE). The overall prevalences of proteinuria and hypertension
      were 47.9% and 62.6%, respectively. Proteinuria was observed more often in
      hypertensive than in non-hypertensive patients (55.2% vs 44.4%, p < 0.05), and in
      patients with diabetes for longer than 10 years (57% vs 40% for diabetes less
      than 10 years, p < 0.05). Although hypercholesterolemia (total cholesterol > or =
      200 mg/dl) was observed in 54% of patients, there was no relationship between
      hypercholesterolemia and proteinuria. In the 79 patients studied in more detail,
      UAE was greater in hypertensive patients compared to non-hypertensive patients
      (606 +/- 15600 mg/24h vs 101 +/- 157 mg/24 h, p < 0.05), and in patients with
      diabetes for 10 years or longer compared to patients in the first decade of
      disease (748 +/- 1732 mg/24 h vs 96 +/- 171 mg/24 h, p < 0.05).
      Hypercholesterolemia and elevated LDL-cholesterol (> 130 mg/dl) were observed in
      56% and 49% of patients, respectively, but were not associated with increased
      UAE. In contrast, hypertriglyceridemia (> 250 mg/dl) was associated with an
      elevated UAE (932 +/- 2150 mg/24 h vs 245 +/- 735 mg/24h, p < 0.05). Increased
      lipoprotein(a) was found in patients with overt albuminuria. In summary, the
      prevalence of risk factors for diabetic nephropathy and associated cardiovascular
      disease is high in Chippewa American Indians in northern Minnesota. Although
      detecting abnormal UAE may be useful in identifying high-risk patients who may
      benefit from early intervention, traditional risk factors such as
      hypercholesterolemia may not explain the risk associated with increased UAE.

PMID- 8869787
TI  - Pseudohypoaldosteronism with normal blood pressure.
AB  - In adults, persistent hyperkalemic distal renal tubular acidosis in the absence
      of impaired renal function is an unusual abnormality usually associated with the
      syndromes of aldosterone deficiency or resistance. Herein, we present an adult
      with a clinical picture consisting of a normal blood pressure of 125/80 mmHg,
      normal blood volume, and glomerular filtration rate, with hyperkalemic distal
      renal tubular acidosis. The patent could spontaneously lower her urine pH to less
      than 5.5. Plasma renin activity was normal. Serum aldosterone level was
      appropriately elevated for the level of serum potassium. Following alkalinization
      of the urine, she was able to generate a urinary to blood PCO2 gradient [U-B
      PCO2] of 55 mmHg, and had a ten fold increased potassium secretion. After salt
      restriction and furosemide administration, her potassium secretion rate increased
      only twofold despite correction of he acidosis. The acidosis, as well as the
      hyperkalemia, was completely corrected after 9-alpha-Fluorohydrocortisone
      administration. Hydrochlorothiazide corrected the acidosis and hyperkalemia.
      Collectively, this picture suggests an underlying chloride shunt as the possible
      pathophysiological mechanism. Our case in unique in that it is not associated
      with hypertension.

PMID- 8869788
TI  - Does the administration of carbicarb lead acutely to back-titration of non
      bicarbonate buffers?
AB  - OBJECTIVE: We have recently demonstrated in a model of acute metabolic acidosis
      in rats that the administration of NaHCO3 does not lead acutely to back-titration
      of non-bicarbonate buffers. Carbicarb is a new alkalinizing agent that has been
      proposed as a replacement for NaHCO3 in the treatment of metabolic acidosis.
      Hence, the purpose of this study was to examine the impact of carbicarb on back
      titration of non-bicarbonate buffers. METHODS: Rats were anaesthetized, intubated
      and ventilated to a PCO2 of approximately 30 mmHg. Acute metabolic acidosis was
      induced by the infusion over 1 hour of 3.5 mmol of hydrochloric acid. After a 20
      min equilibration period, 3 groups of rats (n = 7 in each group) were examined.
      Rats in groups I received 0.75 meq of Na from 1 M carbicarb solution as an
      intravenous bolus, rats in group II received equimolar NaCl, while rats in group
      III were used as time controls. Calculations were performed to quantitate the
      amount of HCO3- that was retained in the ECF volume and the amount that was
      titrated with H+ and excreted as "acid-base" CO2. "Acid-base" CO2 was considered
      as the amount of CO2 that was excreted in excess of what would be produced during
      metabolism. RESULTS: As compared to the NaCl and the time control groups, the
      administration of carbicarb led to significant alkalinization of the ECF, pH rose
      from 7.23 +/- 0.02 to 7.34 +/- 0.03. Of the 0.75 mmol of carbicarb that was
      administered, 0.61 +/- 0.05 mmol (70%) was retained in ECF. There was virtually
      no "acid-base" CO2 produced. CONCLUSIONS: The administration of carbicarb does
      not lead acutely to back-titration of non-bicarbonate buffers especially under
      conditions of fixed ventilation.

PMID- 8869789
TI  - Endotoxin-induced acute renal failure in the rat: effects of urodilatin and
      diltiazem on renal function.
AB  - Acute renal failure (ARF) due to endotoxins is a common problem in clinical
      medicine. Endotoxins are released from the outer membrane of the gram-negative
      bacterial envelope and are composed of lipopolysaccharides (LPS). Although
      systemic hypotension often is present, LPS-induced ARF is characterized by marked
      intrarenal vasoconstriction. Both calcium channel blockers and natriuretic
      peptides are able to antagonize vasoconstricting signals and have been reported
      to exert beneficial effects in toxic and ischemic ARF: We investigated the
      effects of diltiazem (Dil, 300 micrograms/kg) or urodilatin (Uro, 40
      micrograms/kg) or a combination of both (same doses) on renal function in early
      LPS-induced ARF: One hour after induction of ARF by i.v. injection of LPS
      glomerular filtration rate (GFR, clearance of fluorescence-marked inulin) was
      distinctly reduced to about 54% of basal values. In the following infusion period
      (60 min) a significant increase of GFR was observed with diltiazem (1.54 +/- 0.11
      ml/min), urodilatin (1.60 +/- 0.10 ml/min) and the combination of both drugs
      (1.66 +/- 0.04 ml/min) compared to controls (1.17 +/- 0.08 ml/min). Combined
      administration did not cause additive effects. Also 60 and 120 minutes after
      stopping of drug infusion elevated GFR could be maintained in all experimental
      groups. Due to their vasorelaxing activity both Uro and Dil induced a decrease of
      mean arterial blood pressure in comparison with controls and revealed remarkable
      diuretic and natriuretic activity. In conclusion our results underline that
      marked intrarenal vasoconstriction in LPS-induced ARF can be antagonized by the
      well known relaxing potency of Uro and Dil towards vascular smooth muscle and
      mesangial cells. Both Uro and Dil were capable of improving suppressed renal
      function in the early phase of LPS-induced ARF in the rat as long as severe
      systemic hypotension is absent.

PMID- 8869790
TI  - Children on continuous ambulatorial peritoneal dialysis: muscle and plasma
      proteins, amino acids and nutritional status.
AB  - The aim of the study was to investigate plasma and muscle amino acid (AA) levels
      in children on continuous ambulatory peritoneal dialysis (CAPD) and their
      relationship to various indices of nutritional status. Ten children with a mean
      age of 6.4 +/- 5.6 yrs were evaluated. Muscle biopsies and venous blood samples
      were taken after an overnight fast. Muscle samples were obtained from rectus
      abdominis. Data were compared with those of a control group of 22 children who
      were undergoing elective surgery. Informed consent was obtained from the parents.
      The plasma concentration of most of the essential AA (valine, leucine,
      isoleucine, lysine, methionine and tyrosine) were significantly reduced and the
      levels of some non essential AA (aspartic acid, glycine, citrulline, 1-3
      methihystidine, taurine + alanine) were significantly higher than in the
      controls. Muscle intracellular free essential AA concentrations, except the low
      levels of valine and leucine did not differ significantly from values in the
      controls. Among non essential AA, aspartic acid, glutamic acid and ornitine
      showed significantly increased intracellular concentrations. No significant
      correlations were found between plasma and muscle AA concentration and ASP
      (alkali-soluble protein)/DNA ratio, serum albumin, transferrin, bicarbonate
      levels and duration of CAPD. Instead, a significant correlation was noted between
      the muscle ASP/DNA ratio, an indicator of the amount of cell proteins per cell
      unit, and age (r = 0.714, p < 0.05). Muscle Branched chain AA levels were
      significantly correlated to body mass index (BMI) (r = 0.648, p < 0.05).

PMID- 8869791
TI  - Mechanisms and kinetics of the synthesis and release of platelet-activating
      factor (PAF) by polyacrylonitrile membranes.
AB  - Platelet-activating factor is a recognized mediator of anaphylaxis and
      bioincompatibility. Here, the mechanisms and the kinetics of the production of
      platelet-activating factor were studied in vivo during high-flux hemodialysis and
      in vitro in a recirculation model with polyacrylonitrile membranes, the AN-69 and
      the more recent SPAN, where the Na-metallilsulfonate group is partially
      substituted with the less polar methacrylate group. In in vivo studies, eleven
      patients were studied in cross over. Patients were randomly allocated to the AN
      69 (5 patients) and to the SPAN membrane (6 patients) for two weeks. Measurements
      were made in the second week of use. After completion of the second week, the
      patients were switched to the other membrane for a further two weeks. Samples for
      leukocyte and platelet counts, PAF in whole blood or bound to platelets, the C3a
      des Arg and the C5b-C9 membrane attack complex as well as samples for clearances
      of urea, creatinine and phosphates were taken at different time intervals during
      treatment. PAF was detected by biological assay after methanol extraction of
      whole blood or of platelet pellets obtained by sequential centrifugation. C3a des
      Arg and the C5b-C9 fraction were detected by commercially available immunoassays.
      Results were analyzed by Minitab statistical package. PAF was detectable only
      during treatment with AN-69 but not with SPAN 1 min after start of the
      extracorporeal circulation in both whole blood (4.5 +/- 2.7 ng/ml) and on
      platelet surface (4.1 +/- 1.2 ng/ml). No statistical significant differences were
      observed between AN-69 and SPAN with regard to leukocyte and platelet counts,
      plasma C3a des Arg and C5b-C9 levels. The structure modification did not alter
      functional performances as indicated by the lack of statistically significant
      differences in clearance values between the two membranes. In in vitro
      experiments performed with normal washed and whole blood recirculated in a closed
      circuit demonstrated the presence of a plasma-dependent, complement-independent
      mechanisms responsible for the triggering of PAF synthesis and release with AN-69
      but not SPAN membrane. PAF was extractable from the inner and outer side of both
      polyacrylonitrile membranes (AN-69: inner, 4.9 +/- 0.5 ng/ml; outer, 0.1 +/- 0.05
      ng/ml; SPAN: inner, 5.5 +/- 0.6 ng/ml, outer: 3.3 +/- 0.7 ng/ml, SPAN vs. p <
      0.001), suggesting that absorption may be relevant with both membranes.

PMID- 8869792
TI  - Late stenosis of an aortorenal bypass graft fashioned from pericardium.
AB  - Renal artery stenosis (RAS), especially secondary to fibromuscular dysplasia, is
      a curable cause of hypertension in children. Although aortorenal bypass was the
      preferred treatment for this disease twenty years ago, newer techniques are
      available. We report a 27-year-old patient who, at 7 years of age, had severe
      hypertension secondary to RAS in a solitary kidney. Aortorenal bypass with an
      autologous pericardial graft resulted in normal blood pressure for 20 years until
      the pericardial graft thrombosed. Normal blood pressure has again been achieved
      following resection of the stenotic renal artery with reanastomosis to the aorta.

PMID- 8869793
TI  - Delayed onset of diuresis in a patient with acute renal failure due to
      hemorrhagic fever with renal syndrome who also developed anterior
      hypopituitarism.
AB  - A 23-year-old man developed acute renal failure (ARF) due to hemorrhagic fever
      with renal syndrome (HFRS). The patient also developed anterior hypopituitarism
      as a complication of HFRS. The patient's oliguric phase was very much prolonged
      for over 10 days before the diuresis began. The urine output during the oliguric
      phase was near anuric (< 50 ml/day). Interestingly, the patient began to diurese
      just after the institution of glucocorticoid and thyroid hormone replacement
      therapy. The plasma atrial natriuretic polypeptide went up to a smaller peak
      (150.0 pg/ml) at the onset of diuresis compared with 15 other patients (292.4 +/-
      190.4 pg/ml) who did not develop anterior hypopituitarism. The delayed onset of
      diuresis and smaller increase of plasma ANP may have a causal relationship with
      the patient's hypopituitarism.

PMID- 8869794
TI  - Ciliated cells in peritoneal dialysis fluid.

PMID- 8869795
TI  - Polycystic disease associated with intracranial arteriovenous malformation:
      Another extrarenal manifestation?

PMID- 8869796
TI  - Irinotecan (CPT-11): pharmacology and clinical applications.

PMID- 8869797
TI  - The human fibrinolytic system.

PMID- 8869798
TI  - The clinical status of irinotecan (CPT-11), a novel water soluble camptothecin
      analogue: 1996.

PMID- 8869799
TI  - Clinical use of hematopoietic growth factors.
AB  - With the identification of recombinant production of the hematopoietic growth
      factors, these cytokines have been evaluated in the treatment of primary bone
      marrow failure states and after myelosuppressive chemo- or radiotherapy.
      Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating
      factor, and erythropoietin have been approved for clinical use, and others
      including c-mpl-ligand (also called megakaryocyte growth and development factor
      or thrombopoietin) are in phase I and II trials. Most studies have been done with
      granulocyte and granulocyte-macrophage colony-stimulating factors; their
      beneficial effects are proven regarding acceleration of granulocyte recovery
      after chemo- and radiotherapy. In the majority of trials, this acceleration
      results in a reduction of infectious risks, a shortening of drug- and radiation
      induced myelosuppression, and a higher chemotherapy dose intensity; however, an
      improved remission rate and improved long-term survival rates have not yet been
      definitively documented. Guidelines have been published to provide a rational
      basis for the use of these factors in clinical practice. It should be emphasized,
      however, that for many of the recommendations data from randomized clinical
      trials are lacking.

PMID- 8869800
TI  - Prevention of infection in neutropenic cancer patients.
AB  - The prophylactic or pre-emptive approach should help to restrict use of
      antibiotics and lead to better management of infection. It is clear that if
      effective pre-emptive therapy is available (be it as prophylaxis), the empiric
      additions of other agents should be taken into account and tailored accordingly.
      On the other hand, prophylaxis carries the risk of resistance emergence, and
      subsequent microbiological investigations and empiric therapy should be selected
      taking that risk into account. We definitely need more studies integrating both
      pre-emptive therapy (also called prophylaxis) and empiric therapy for febrile
      episodes. Both interventions are to be seen as a continuous action rather than as
      two consecutive steps in the approach of the neutropenic patient. Finally, all
      neutropenic patients are not identical, and thus, they do not require identical
      approaches. It might well be that prophylaxis is needed only in some subsets of
      the neutropenic population and not in others.

PMID- 8869801
TI  - The role of supportive care in quality of life.
AB  - Supportive care interventions are usually given with the intent of improving
      quality of life. Until recently, however, even studies of palliative
      interventions have infrequently incorporated some measure of overall benefit.
      This article reviews those recent supportive care studies that have attempted to
      measure either quality of life or some benefit other than improvement in a single
      symptom. Some palliative chemotherapy studies did indeed demonstrate measurable
      improvement in overall well-being, and some commonly cited supportive approaches
      were associated with a significant detriment in health-related quality of life.

PMID- 8869802
TI  - Cytogenetics and experimental models.
AB  - Cytogenetic analysis plays a direct, potentially decisive role in the examination
      of benign and malignant bond and soft tissue tumors. Translocations, or the
      exchange of chromosomal material between two or more nonhomologous chromosomes,
      are frequently encountered as tumor-specific anomalies in mesenchymal neoplasms.
      The consequences of many of these translocations has been the formation of
      chimeric proteins with features characteristic of altered transcription factors.
      Recent studies have revealed new tumor-specific translocations (eg, cemento
      ossifying fibroma and myxoid chondrosarcoma) and the association of established
      translocations, eg, t(11;22) and t(12;16), in rare histologic subtypes such as
      biphenotypic sarcomas with myogenic and with neural differentiation and round
      cell liposarcoma, respectively. In contrast to a single translocation, many
      mesenchymal neoplasms such as malignant fibrous histiocytoma and osteosarcoma are
      characterized by multiple, often complex, chromosomal abnormalities. Recent
      advances in molecular cytogenetics, eg, in situ hybridization and comparative
      genomic hybridization, have made the identification of many of these
      abnormalities possible and in some instances, have revealed chromosomal
      imbalances not detectable with traditional cytogenetic analysis.

PMID- 8869803
TI  - Diagnosis and treatment of soft tissue sarcomas in adults.
AB  - Soft tissue sarcomas account for approximately 1% of all malignancies. They
      constitute a wide range of different tumor types with very different clinical
      courses and treatment sensitivities. Our understanding of the molecular
      mechanisms of tumor growth in sarcomas is increasing rapidly. These new data will
      probably lead to drastic changes in our current classification systems, which are
      primarily based on routine microscopy. This might also bring about a more
      detailed and reliable prognostic evaluation in individual tumors. Hopefully, this
      knowledge will guide us towards a more rational and more successful development
      of new therapies. Current surgical approaches and treatment protocols are more or
      less well defined. Knowledge on when to use ionizing radiation for local control
      is reasonably clear. Major difficulties however remain for both these treatment
      modalities in cases of both truncal and retroperitoneal sarcomas. The lack of new
      very active chemotherapeutic agents against this group of diseases has remained
      unchanged in the past years, although both the taxanes and the topoisomerase I
      inhibitors show some activity.

PMID- 8869804
TI  - Osteosarcoma and other tumors of bone.
AB  - Steady progress in the delineation of prognostic factors and the identification
      of genetic alterations and of potential mechanisms of oncogenesis mark the
      contributions to the literature on osteosarcoma for the past year. A new cytokine
      and chemotherapy combination has shown promise, and additional work on
      chemotherapy regimens containing ifosfamide will undoubtedly stimulate interest
      in a new generation of randomized clinical trials that will be essential for
      further refinement of therapy for osteosarcoma.

PMID- 8869805
TI  - Ewing's sarcoma and extracranial primitive neuroectodermal tumors.
AB  - The Ewing's family of tumors is comprised of bone and soft tissue, small round
      blue cell neoplasms of neuroectodermal origin defined by the chromosomal
      aberration t(11;22)(q24;q12), and closely related variants. Molecular methods now
      exist to facilitate diagnosis and to defect minimal residual disease. Multiagent
      chemotherapeutic regimens in concert with adequate local control yield improved
      survival rates in patients with localized disease at diagnosis. Patients with
      metastatic disease still suffer poor survival rates; programs attempting to cure
      metastatic patients with intensive therapy as facilitated by peripheral stem cell
      and autologous marrow rescue have shown some promise. Intensive regimens with and
      without rescue are being explored for high-risk patients.

PMID- 8869806
TI  - Rhabdomyosarcoma and other soft tissue sarcomas in children.
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma in children and
      adolescents. During the 1960s, use of surgery and radiation therapy for local
      control led to survival in fewer than one third of children with this malignancy.
      Multimodal therapy (chemotherapy, radiation therapy, and surgery), refinements in
      tumor staging, and better supportive care have significantly improved outcome
      among children with rhabdomyosarcoma, with long-term survival rates approaching
      70%. In contrast, little is known about a heterogeneous group of pediatric soft
      tissue sarcomas collectively termed nonrhabdomyosarcoma sort tissue sarcomas
      (NRSTSs). Response of NRSTSs to chemotherapeutic agents has been disappointing,
      and long-term remissions following chemotherapy are rare. Because the value of
      adjuvant therapy remains unproven, surgery is the mainstay of therapy for these
      tumors. This article presents clinical and biological findings of the past year
      that have significantly contributed to our understanding of rhabdomyosarcoma and
      NRSTSs.

PMID- 8869807
TI  - New systemic drugs in the treatment of gastrointestinal cancer.
AB  - Paclitaxel has shown a significant activity on esophageal cancer in a phase II
      trial. Irinotecan has established the single-agent efficacy on both gastric and
      colorectal cancer. Docetaxel has attained a significant activity on advanced
      gastric cancer and a 29% response rate on pancreatic cancer in a phase II trial.
      Tomudex has shown comparable activity to leucovorin and 5-fluorouracil in
      colorectal cancer.

PMID- 8869808
TI  - Neoadjuvant therapy for upper gastrointestinal tract cancers.
AB  - Esophageal, gastric, and pancreatic cancers frequently present with extensive
      local regional disease, which can be difficult to resect or to definitively
      control with radiation therapy given as a single modality. In addition, these
      patients are at high risk for the development of distant metastasis. Neoadjuvant
      chemotherapy is a promising experimental approach for the use of combined
      modality treatments that involve a systemic component. The theoretical background
      for the use of chemotherapy followed by an operation or chemotherapy plus
      radiation in these tumors has been extensively described. For esophageal cancer,
      many phase II trials have demonstrated tolerance to systemic chemotherapy;
      chemotherapy plus radiation prior to operation has more toxicity. Definitive
      phase III studies testing the hypothesis that this approach is superior to
      operation alone have recently been performed in the United States and Europe.
      These data are currently being analyzed. For the use of combined modality therapy
      of chemoradiation, random assignment trials have demonstrated an improvement in
      cure rate for patients with squamous cell carcinomas of the esophagus.
      Preliminary data suggest a similar outcome for adenocarcinoma, but the number of
      patients who have been studied is smaller. Newer phase III studies involve the
      use of new systemic agents that have demonstrated activity in metastatic disease
      (such as paclitaxel) or the use of higher doses of radiation therapy. For gastric
      cancer, a substantial number of phase II trials have again demonstrated tolerance
      to preoperative chemotherapy with no increase in operative morbidity or
      mortality. Small-scale phase III trials have been performed that suggest an
      improvement in outcome. Definitive studies are in the planning stage. Finally,
      for pancreatic carcinoma, in which local control is an even more difficult issue,
      a major stumbling block remains the development of newer systemic therapies that
      have activity in this disease. The recent identification of gemcitabine as having
      modest activity as a single agent and its potential use with radiation therapy is
      being explored in the neoadjuvant setting.

PMID- 8869809
TI  - Organ preservation in anal and rectal cancers.
AB  - For the past 10 to 15 years, radiation therapy and chemotherapy have played an
      increasingly important role in the treatment of various gastrointestinal
      malignancies, most prominently in anal and rectal cancer. Critical issues in the
      care of patients with anal and rectal cancer include not only local control and
      survival but organ preservation as well. For patients with carcinoma of the anal
      canal, external-beam irradiation with 5-fluorouracil and chemotherapy with
      mitomycin C have replaced surgery as primary therapy. Current studies are
      optimizing this therapy. In contrast, the management of distal rectal cancer is
      in evolution. Although the abdominoperineal resection has been long regarded as
      the definitive treatment of distal rectal cancer, it is associated with
      substantial morbidity (loss of anorectal function with a permanent colostomy and
      a high incidence of sexual and genitourinary dysfunction). As an alternative,
      treatment programs utilizing sphincter-preserving procedures with radiation
      therapy and chemotherapy are under active investigation. In selected patients,
      these strategies appear promising, and there have been reports of satisfactory
      local control and survival, as well as preservation of sphincter integrity.

PMID- 8869811
TI  - Supportive care.

PMID- 8869810
TI  - Chronotherapy for gastrointestinal cancers.
AB  - Chronotherapy consists in the administration of medicines according to biological
      rhythms. Further insight into the mechanisms of the circadian system has led to
      adapting the delivery of cancer chemotherapy to rhythms in drug metabolism or
      cell proliferation. The pharmacology of anticancer agents has long been known to
      vary largely and predictably according to dosing time in mice or rats. Portable
      programmable multi-channel pumps allowed demonstration of the clinical relevance
      of the chronotherapy principle in a sufficiently large patient population. This
      demonstration was achieved using a 5-day infusion of 5-fluorouracil, leucovorin,
      and oxaliplatin in patients with colorectal cancer metastases. A further
      innovation was that oxaliplatin, a new drug whose activity in this disease was
      first shown using chronomodulated infusion, was incorporated early in this novel
      three-drug regimen, in view of the good tolerability of this administration
      schedule. The fully ambulatory nature of treatment courses was an additional
      constraint put on chronotherapy. More than 1000 patients with metastatic
      gastrointestinal malignancies have now received chronotherapy protocols in
      several countries from North America or Europe. Results have clearly indicated
      that this approach improved chemotherapy tolerance and allowed safe increases in
      drug doses. A clinical phase III trial compared a flat versus the chronomodulated
      three-drug regimen, and demonstrated large, simultaneous improvements in both
      tolerability and response rates in patients with metastatic colorectal cancer
      receiving chronotherapy. This approach may also be beneficial to patients with
      other gastrointestinal malignancies, and it was amenable to combination with
      surgery and radiotherapy. It also appeared suitable for devising potentially more
      active dose-intensive yet safe regimens. Incorporation of chronopharmacology into
      the development stages of new drugs may improve their safe use to the greatest
      benefit of both cancer patients and new drug development, as was done for
      oxaliplatin.

PMID- 8869812
TI  - Sarcomas.

PMID- 8869813
TI  - Gastrointestinal tract.

PMID- 8869814
TI  - Metabolism of racemic 3,4-methylenedioxyethylamphetamine in humans. Isolation,
      identification, quantification, and synthesis of urinary metabolites.
AB  - Studies on the isolation, identification, quantification, and synthesis of the
      urinary metabolites of racemic 3,4-methylenedioxyethylamphetamine (MDE) in humans
      are presented. After oral administration of 140 mg of racemic MDE to healthy
      volunteers, the following phase I metabolites could be isolated and identified by
      GC/MS: unchanged racemic MDE (I), racemic 3,4-dihydroxyethylamphetamine (II),
      racemic 4-hydroxy-3-methoxyethylamphetamine (IIIa), racemic 3,4
      methylenedioxyamphetamine (IV), racemic 3,4-dihydroxyamphetamine (V), racemic 4
      hydroxy-3-methoxyamphetamine (VIa), methylenedioxyphenylacetone (IXa), 3,4
      methylenedioxyhippuric acid (X), and hydroxymethoxyhippuric acid (XII). The
      probable intermediate metabolite 3,4-dihydroxyhippuric acid (XI) could not be
      detected. Therefore, two overlapping phase I metabolic pathways for racemic MDE
      in humans could be postulated. The first and predominant pathway leads, via ring
      degradation by O-dealkylation, to the corresponding 3,4-dihydroxy metabolites,
      which are subsequently methylated at the hydroxyl group at position 3 of the
      aromatic ring. The second pathway leads, via side chain degradation by N
      dealkylation, to the corresponding primary amines (IV, V, and VI). Oxidative N
      deamination forms the substituted phenylacetones, which are degraded to the
      corresponding benzoic acids. This is followed by conjugation with glycine to form
      substituted hippurates. The structures of all of these metabolites were confirmed
      by chemical syntheses, which are described in this paper. All of the metabolites
      containing hydroxy groups are partly excreted in a conjugated form, because the
      amounts of these metabolites were much higher in urine extracts after enzymatic
      cleavage of conjugates. Quantification of the urinary excretion by HPLC revealed
      that 19% of the MDE dose was eliminated as I, 31.6% as IIIa, and 2.8% as IV
      within 32 hr.

PMID- 8869815
TI  - Sequestered endoplasmic reticulum space for sequential metabolism of
      salicylamide. Coupling of hydroxylation and glucuronidation.
AB  - The metabolic disposition of simultaneously delivered [14C]salicylamide (SAM)
      (100 microM) and a tracer concentration of its hydroxylated metabolite
      [3H]gentisamide (GAM) was studied with single-pass followed by recirculating rat
      liver perfusion (10 ml/min). The use of dual radiolabeling of precursor-product
      pairs in single-pass and recirculating perfusions allowed for characterization of
      the differential metabolism of preformed [3H]GAM and formed [14C]GAM, which arose
      in situ in the liver with [14C]SAM single-pass perfusion, and the behavior of
      circulating [14C]GAM, which behaved as a preformed species in recirculation. In
      both modes of perfusion, [14C]SAM was mainly sequentially metabolized to [14C]GAM
      5-glucuronide, whereas [3H]GAM predominantly formed [3H]GAM-5-sulfate. The steady
      state and time-averaged clearances of SAM were identical and approached the value
      of flow, yielding a high hepatic extraction ratio (E = 0.98). The apparent
      extraction ratio of formed GAM [E(mi) = 0.96] was greater than that of the
      preformed species [E(pmi) approximately 0.7]. Because the coupling of (SAM)
      oxidation and (GAM) glucuronidation was a plausible explanation for the
      observation, a novel physiological pharmacokinetic model was developed to
      interpret the data. In this model, the liver was divided into three zonal units,
      within which acinar distribution of enzymatic activities was considered, namely
      periportal sulfation, evenly distributed glucuronidation, and perivenous
      hydroxylation. Each zonal region was subdivided into extracellular, cytosolic,
      and endoplasmic reticulum compartments, with cytosolic (sulfotransferases) and
      microsomal (cytochromes P-450 and UDP-glucuronosyltransferase) enzymes being
      segregated intracellularly into the cytosolic compartment and endoplasmic
      reticulum compartment, respectively. The simulations provided a good prediction
      of the present experimental data as well as previously obtained data with
      increasing SAM concentration and retrograde flow and supported the contention
      that SAM oxidation and GAM glucuronidation are coupled.

PMID- 8869816
TI  - Metabolism of aceclofenac in humans.
AB  - Metabolism of the new nonsteroidal antiinflammatory drug aceclofenac ([2-(2',6'
      dichlorophenylamino)phenyl]acetoxyacetic acid) was investigated both in the in
      vitro hepatic human models and in vivo. Aceclofenac is metabolized in human
      hepatocytes and human microsomes to form [2-(2',6'-dichloro-4'-hydroxy-
      phenylamino)phenyl]acetoxyacetic acid as the major metabolite, which is then
      further conjugated. Minor metabolites were [2-(2',6'-dichlorophenylamino)-5
      hydroxyphenyl]acetoxyacetic acid and [2-(2',6'-dichlorophenylamino)phenyl]acetic
      acid, as well as the hydroxylated derivatives [2-(2',6'-dichloro-4'-
      hydroxyphenylamino)phenyl]acetic acid and [2-(2',6'-dichlorophenylamino)- 5
      hydroxyphenyl]acetic acid. After oral administration to human volunteers (100 mg,
      single dose), aceclofenac reached a Cmax value of 7.6 +/- 1.3 micrograms/ml and a
      tmax of 2.6 +/- 1.8. The same metabolites as those detected in cell culture or
      microsome incubations were found in 12-hr urine after an oral administration of
      100 mg aceclofenac to human volunteers. Cytochrome 2C9 is the enzyme responsible
      for the hydroxylation at position 4'. This could be demonstrated by: 1) selective
      inhibition by sulfaphenazole; 2) correlation between the formation of the
      hydroxylated metabolite and tolbutamide hydroxylase activity; and 3) formation of
      this metabolite only when incubated with microsomes obtained from cells
      expressing human cytochrome 2C9. However, no conclusive information could be
      obtained concerning the cytochrome catalyzing the hydroxylation at position 5.
      The comparison between human microsomes and human hepatocytes metabolism on one
      hand, and human in vivo metabolism on the other, supports human hepatocytes in
      primary culture as the model that best anticipated the metabolism of the drug in
      vivo.

PMID- 8869817
TI  - Reactivity of mefenamic acid 1-o-acyl glucuronide with proteins in vitro and ex
      vivo.
AB  - Mefenamic acid is a nonsteroidal anti-inflammatory drug commonly used in
      analgesia. The use of this drug has been implicated in several cases of
      nephrotoxicity including acute renal failure and tubulointerstitial nephritis.
      One theory of drug-induced tubulointerstitial nephritis is that the drug or a
      derivative of the drug becomes irreversibly bound to certain sites in renal
      tissue and an immune response is directed against the hapten-host conjugate.
      Previous studies have shown that in humans the nonsteroidal anti-inflammatory
      drug mefenamic acid is metabolized by both phase I enzymes and the phase II
      enzyme family UDP-glucuronosyltransferase. Indeed, three glucuronides were
      identified and isolated from human urine by semipreparative HPLC after oral
      administration of mefenamic acid. This study focuses on mefenamic acid
      glucuronide and further characterizes this acyl glucuronide in terms of stability
      and its ability to bind irreversibly to proteins. Stability studies of mefenamic
      acid glucuronide in aqueous buffer highlighted the relative stability of this
      acyl glucuronide at physiological pH. The half-life at 37 degrees C, pH 7.4, was
      16.5 +/- 3.1 hr, which is considerably longer than those reported for many acyl
      glucuronides. The degradation of mefenamic acid glucuronide was accelerated under
      alkaline conditions, decreasing the half-life to 5 +/- 1.6 hr at pH 8.0.
      Mefenamic acid glucuronide, although extremely stable in buffer at physiological
      pH, was found to bind irreversibly to human serum albumin in vitro. Irreversible
      binding to cellular proteins in culture was also evident with the addition of
      mefenamic acid to the heterologous Chinese hamster lung fibroblast cell line V79
      expressing the human UDP-glucuronosyltransferase isoenzyme UGT1*02. This binding
      was directly related to glucuronide formation, because irreversible binding was
      not evident in the untransfected cell line V79.

PMID- 8869818
TI  - Effects of ethanol and cocaethylene on cocaine pharmacokinetics in conscious
      dogs.
AB  - Coingestion of cocaine and ethanol is common among cocaine users, and this
      combination is reported to enhance the euphoric effects of cocaine. The
      cardiovascular effects of cocaine are increased in the presence of ethanol,
      although the mechanism(s) involved in this interaction are poorly understood.
      Recent studies suggest the enhanced cardiac effects may be caused by ethanol
      mediated inhibition of cocaine metabolism leading to higher cocaine plasma
      concentrations. However, these studies were all performed in animals or humans
      that form cocaethylene when ethanol and cocaine are coadministered. Thus, it is
      also possible that cocaethylene could inhibit cocaine's metabolism. Preliminary
      studies in our laboratory indicate the dog does not form detectable quantities of
      cocaethylene after coadministration of cocaine and intravenous ethanol. Thus, the
      dog may be a useful model for isolating the individual contributions of ethanol
      and cocaethylene to this interaction. The purpose of the present study was to
      confirm this observation, and to determine the effects of ethanol and
      cocaethylene on cocaine pharmacokinetics in the conscious dog. Six dogs received
      cocaine (3 mg/kg i.v.) alone, ethanol (1 g/kg i.v.) followed by cocaine (3 mg/kg
      i.v.), and cocaine (3 mg/kg i.v.) + cocaethylene (3 mg/kg i.v.). Cocaethylene was
      not detected in any of the plasma samples from the six dogs after administration
      of cocaine and ethanol. Ethanol and cocaethylene reduced mean cocaine clearance
      by 47% and 26%, respectively. Inhibition of cocaine's metabolism by both ethanol
      and cocaethylene may play an important role in mediating the enhanced effects of
      cocaine in the presence of ethanol.

PMID- 8869819
TI  - Regulation of hepatic sulfotransferases by steroidal chemicals in rats.
AB  - Pregnenolone-16 alpha-carbonitrile (PCN) has previously been shown to increase
      sulfotransferase (ST) activity in rats. It was of interest to determine whether
      other steroids, such as dexamethasone (DEX), similarly affect ST activity, and
      whether they alter ST gene expression. The modulation of rat liver STs by the two
      steroidal compounds was examined at both the enzyme activity and mRNA levels. PCN
      (75 mg/kg daily for 4 days) increased liver phenol ST activity toward 1-naphthol
      and estrone, and hydroxysteroid ST activities toward dehydroepiandrosterone
      (DHEA) and bile acids; but, PCN had no effects on ST activities toward dopamine
      and N-hydroxy-2-acetylaminofluorene (N-OH-2AAF). DEX (50 mg/kg daily for 4 days)
      had similar effects on ST activities toward 1-naphthol, estrone, and DHEA, but
      DEX markedly increased ST activity toward dopamine and suppressed the N-OH-2AAF
      ST activity. Northern-blot analysis showed that PCN (75 mg/kg, single injection)
      had no effects on mRNA levels of phenol ST (ST1A1), N-OH-2AAF ST (ST1C1), and
      estrogen ST (ST1E2), but PCN significantly increased mRNA levels of
      hydroxysteroid ST (ST-20/21, ST-40/41, and ST-60). DEX (50 mg/kg, single
      injection), in contrast, increased the mRNA levels of ST1A1 and tended to
      suppress ST1C1, which corresponds to changes in encoded ST activity. Although DEX
      increased ST activity toward DHEA, as did PCN, DEX had less effect on
      hydroxysteroid ST mRNA levels. These results suggest that STs are regulated by
      steroids, but DEX and PCN regulate the STs differently. The change in ST enzyme
      activity seems to be partially caused by alteration in mRNA levels.

PMID- 8869820
TI  - In vitro metabolism of atrazine, terbuthylazine, ametryne, and terbutryne in
      rats, pigs, and humans.
AB  - The in vitro metabolism of four s-triazine herbicides (atrazine, terbuthylazine,
      ametryne, and terbutryne) was studied using liver microsomes from rats, pigs, and
      humans. New HPLC methods with UV detection were developed for the analyses of the
      incubations. Principal phase I reactions were N-monodealkylation, hydroxylation
      of the isopropyl or tert-butyl moiety, and sulfoxidation of the substrates in all
      species. Bidealkylation, 2-hydroxylation, or cleavage of the tert-butyl moiety
      could not be found in this system. The sulfoxidation of the 2-methylthio-s
      triazines exceeded catalysis of the other metabolic reactions by 3-4-fold in all
      species. In general, all species produced the same types of metabolites, but with
      species-specific differences in the ratios of the metabolites. Species-specific
      stereoselective formation of a new chiral isopropyl-hydroxylated metabolite from
      atrazine was investigated using chiral HPLC techniques. The stereoselective
      production of this metabolite was different in the different species, with S/R
      ratios of 76:24 in rats, 49:51 in pigs, and 28:72 in humans.

PMID- 8869821
TI  - Metabolism and toxicity of 4-hydroxyphenylacetone in rat liver slices: comparison
      with acetaminophen.
AB  - Acetaminophen is oxidized by cytochrome P450 to a reactive quinone imine, N
      acetyl-p-benzoquinone imine, which is thought to be responsible for its
      hepatotoxic effects. 4-Hydroxyphenylacetone (4-HPA) is a structural analog of
      acetaminophen in which the amine group is replaced by a methylene group.
      Following a similar metabolic pathway, 4-HPA would be oxidized to form a reactive
      quinone methide intermediate. We compared the metabolism and toxicity of 4-HPA
      and acetaminophen in liver microsomes and precision-cut liver slices from male
      Sprague-Dawley rats. Both 4-HPA and acetaminophen formed glutathione conjugates
      in microsomal incubations. 4-HPA formed diastereomeric glutathione conjugates,
      which is consistent with the formation of an intermediate quinone methide. The
      rate of conjugate formation with 4-HPA was 8.5-fold greater than that with
      acetaminophen. In rat liver slices a concentration of 5 mM 4-HPA killed
      approximately 50% of hepatocytes after 6 hr of incubation, whereas acetaminophen
      was not toxic at concentrations up to 50 mM. N-Acetylcysteine protected slices
      from 4-HPA-induced toxicity, whereas phenobarbital enhanced metabolism and
      toxicity. In summary, 4-HPA is more hepatotoxic than acetaminophen, and this may
      be the result of differences in the metabolic rate and/or the type of reactive
      intermediate formed.

PMID- 8869822
TI  - Cytochrome P4503A is the major source of N-vinylprotoporphyrin IX formation after
      administration of 3-[2-(2,4,6-trimethylphenyl)thioethyl]-4-methylsydnone to
      untreated and dexamethasone-pretreated rats.
AB  - The sydnone, 3-[2-(2,4,6-trimethylphenyl)thioethyl]-4-methylsydnone (TTMS), which
      has previously been shown to cause mechanism-based inactivation of rat hepatic
      cytochrome P450 (P450) 1A and 3A, was shown to cause in vitro mechanism-based
      inactivation of rat P450s 2B1, 2C6, and 2C11, but not of P4502A1/2.
      Administration of TTMS to rats is known to cause degradation of rat hepatic P450
      by heme N-alkylation yielding N-vinylprotoporphyrin IX (N-vinylPP). Pretreatment
      of rats with beta-naphthoflavone (beta NF) failed to increase hepatic N-vinylPP
      after TTMS administration. Because beta NF causes a marked increase in hepatic
      levels of P4501A, we conclude that P4501A of rat liver is not a quantitatively
      important source of N-vinylPP from TTMS. The increased formation of N-vinylPP in
      phenobarbital (PB)- and dexamethasone (DEX)-pretreated rats suggested that an
      inducible P450 isozyme (e.g. P4502B1/2, P4503A, or both) is/are an important
      contributor to N-vinylPP formation from TTMS. When troleandomycin (TAO) (a
      selective inhibitor of P4503A) was coadministered with TTMS, N-vinylPP formation
      was reduced to 25% of control in DEX-pretreated rats and to 34% of control in
      untreated (UT) rats, showing that P4503A was quantitatively the major source of N
      vinylPP formation in UT- and DEX-pretreated rats. No significant differences were
      found in the formation of the ring A-substituted (NA), ring B-substituted (NB),
      ring C-substituted (NC), and ring D-substituted (ND) regioisomers of N-vinylPP
      among UT, beta NF-, PB-, or DEX-pretreated rats. Regioisomer data, in addition to
      data obtained with TAO, indicate that a single inducible form of P450, namely
      P4503A, is responsible for the bulk of N-vinylPP formation in UT and DEX
      pretreated rat liver after TTMS administration.

PMID- 8869823
TI  - Purification and characterization of a medium chain acyl-coenzyme A synthetase.
AB  - Glycine conjugation is an important route of detoxification of many xenobiotic
      and endogenous carboxylic acids. A medium chain acyl-coenzyme A synthetase that
      catalyzes the first reaction of glycine conjugation was purified from bovine
      liver mitochondria by chromatographies on anion exchange, hydroxylapatite,
      affinity, and finally by gel filtration. The purified enzyme not only conjugates
      medium chain fatty acids, but also aromatic and arylacetic acids. The highest
      activity was shown with hexanoic acid. High activities were observed for benzoic
      acid derivatives with large alkyl and alkoxyl groups in the para- or meta
      positions of the benzene ring. Ortho-substituted derivatives exhibited no
      activity. The enzyme was inhibited by iodoacetamide and salicylic acid, and
      activated by albumin. Salicylic acid was a competitive inhibitor of the enzyme,
      with an apparent Ki value of 37 microM. Enzyme activity increased 74% when the pH
      was raised from 7 to 10. Molecular weight of the purified medium chain acyl
      coenzyme A synthetase was 65.5 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis.

PMID- 8869824
TI  - Expression of CYP2A genes in rodent and human nasal mucosa.
AB  - CYP2A10 and CYP2A11, which are abundant in olfactory microsomes from rabbits, are
      active in the metabolic activation of a number of nasal toxicants, such as
      hexamethylphosphoramide and N-nitrosodiethylamine. Previous immunohistochemical
      studies indicated that CYP2A-related cytochromes P450 may also be present in
      rodent and human olfactory tissue. In the present study, the expression of
      cytochromes P450 highly homologous to rabbit CYP2A10/11 in rat, mouse, and human
      nasal mucosa was studied. In Sprague-Dawley rats, CYP2A3 mRNA was detected in
      olfactory mucosa at levels much higher than those found in total RNA from lung.
      Similar observations were made for the level of microsomal CYP2A3 protein with
      the use of antibodies to rabbit CYP2A10/11. However, mRNAs for two other rat
      cytochrome P450 genes in the CYP2A subfamily, CYP2A1 and CYP2A2, were not
      detected in nasal tissue by RNA-polymerase chain reaction analysis. In C57BL/6
      mice, both CYP2A4 and CYP2A5 mRNAs were detected in the olfactory mucosa by RNA
      polymerase chain reaction, but the CYP2A5 transcript was present at a level much
      higher than that of CYP2A4. The expression of another mouse gene in CYP2A
      subfamily, CYP2A12, was not detected in nasal tissue. CYP2A5 protein was also
      detected in mouse olfactory microsomes at higher levels than in liver, lung, or
      kidney microsomes. However, no significant sex differences in the levels of
      CYP2A4/5 mRNA or microsomal coumarin 7-hydroxylase activity were found with the
      nasal tissue. In addition, consistent with previous immunohistochemical studies,
      the expression of CYP2A6 in human nasal mucosa was detected by RNA-polymerase
      chain reaction as well as RNA blot analysis. The identification of CYP2A6 in
      human nasal tissues may have important implications for risk assessment of
      potential nasal toxicants, and the abundant expression of the CYP2A genes in rat
      and mouse olfactory tissue suggests a molecular basis for the known tissue
      specific toxicity of numerous inhaled compounds in rodents.

PMID- 8869825
TI  - Identification of tissue-specific DNase I hypersensitive sites in the rabbit
      flavin-containing monooxygenase form 2 gene.
AB  - Previous studies demonstrated that the flavin-containing monooxygenases (FMO) are
      expressed in a tissue-specific manner. To begin an elucidation of mechanisms
      regulating this expression pattern, genomic clones for rabbit FMO2 were isolated
      and characterized. Two clones were isolated from a lambda EMBL3 genomic library
      and shown to span approximately 30 kilobase pairs but to contain only about 800
      base pairs of coding information. Primer extension analysis was used to map the
      transcription start site, extending the previously published cDNA sequence by 17
      base pairs. The FMO2 promoter does not utilize a classical TATA box, nor are HTF
      islands present (DNA domains rich in cleavable sites for 5-methyl
      cytidine/guanosine-sensitive restriction enzymes). Rather, homology with
      promoters controlled by initiator elements is observed. Previous studies
      demonstrated FMO2 expression in rabbit pulmonary Clara and type II cells [Overby,
      Nishio, Lawton, Plopper, and Philpot: Exp. Lung Res. 18, 131, (1992)]. In the
      present study, a highly enriched Clara/type II cell population was prepared, and
      the FMO2 gene was analyzed for DNase I-hypersensitive and methylated regions.
      These data were then contrasted with those obtained from a similar analysis of
      the nonexpressed, hepatocyte FMO2 gene. No difference in the methylation status
      was observed. However, Clara/type II cell-specific DNase I-hypersensitive sites
      are located within the promoter region of the FMO2 gene. Thus, tissue-specific
      transcription factors likely are more prominent than methylation in regulating
      FMO2 expression. Consistent with this observation, both polyomavirus enhancer
      activator 3 (E26 transformation specific) and thyroid transcription factor 1
      consensus sequences are present within the tissue-specific DNase I-hypersensitive
      domain.

PMID- 8869826
TI  - Expression of cytochromes P450 in human breast tissue and tumors.
AB  - In an effort to determine which members of the cytochrome P450 (CYP) superfamily
      are expressed in human breast tissue and tumors, RNA-polymerase chain reaction
      studies have been undertaken. Detection of expressed CYP mRNAs identifies those
      forms of the enzyme that are capable of expression in breast tissue, and provides
      insight into the potential for in situ xenobiotic and therapeutic drug
      metabolism. CYP1A1 mRNA was present in (5/11) breast tissues and (6/13) tumors.
      When normal and tumor tissues were from the same individuals, higher
      amplification occurred in normal tissues. CYP1B1 mRNA was present in all but one
      tissue, and CYP2C mRNA forms were present in all of the tissues. CYP3A4 mRNA was
      present in (8/11) normal breast tissues and (2/13) tumor tissues, and CYP3A5 mRNA
      was present in (9/11) normal tissues and (2/13) tumor tissues. The expression of
      the CYP3A mRNA forms was not coincident, suggesting differential regulation.
      CYP2D6 mRNA was present in (10/11) normal breast tissue and (10/13) tumors. Two
      splice variants of CYP2D6 mRNA were also detected; one with a 207 bp intron
      spliced in was detected in all of the normal tissue samples and (11/13) tumors,
      whereas another (which lacks a 3'-portion of exon 6) was detected in (9/11)
      normal breast tissues and (7/13) tumors. Thus, examples of each of the xenobiotic
      metabolizing CYP1, CYP2, and CYP3 subfamilies were detected in low levels in
      human normal breast tissue and tumors. The machinery for possible in situ
      bioactivation of xenobiotics and modification of therapeutic drugs is thus
      present in human breast tissue.

PMID- 8869827
TI  - Biotransformation of the aerosol propellant 1,1,1,2,3,3,3-heptafluoropropane (HFA
      227): lack of protein binding of the metabolite hexafluoroacetone.
AB  - The biotransformation of the aerosol propellant 1,1,1,2,3,3,3-heptafluoropropane
      (HFA-227) was investigated in rats in vivo and in rat and human liver microsomes.
      In the urine of rats exposed to 5000 ppm HFA-227 for 6 hr, very small amounts of
      hexafluoroacetone trihydrate were identified as an HFA-227 metabolite by 19F-NMR.
      Fluoride concentrations in the urine samples (0-48 hr after the end of the
      exposure) from exposed animals were not significantly different from those found
      in samples from nonexposed rats. In rat and human liver microsomes, fluoride and
      hexafluoroacetone trihydrate formation from HFA-227 was detected in very low
      levels only in liver microsomes from pyridine-treated rats and in two of eight
      human liver microsome samples, which exhibited the highest cytochrome P4502E1
      activities. Because some aldehydes may covalently bind to proteins and the
      formation of fluorinated protein adducts has been implicated in immune-mediated
      hepatitis induced by halothane, the binding of hexafluoroacetone trihydrate to
      proteins was also investigated. Hexafluoroacetone trihydrate also gave only a
      very small resonance in fluorine NMR experiments when binding to human serum
      albumin was studied in comparison with the acylating agent S
      ethyltrifluoroacetate. Moreover, no fluorine-containing products were formed by
      the reaction of hexafluoroacetone trihydrate with N alpha-acetyl-L-lysine, and
      hexafluoroacetone trihydrate was not metabolized to fluorine-containing
      metabolites or inorganic fluoride in rats. Comparative studies in human liver
      microsomes demonstrated that a halothane metabolite may covalently bind to
      proteins; in contrast, metabolism and covalent binding of HFA-227 could not be
      demonstrated. In summary, these data indicate that HFA-227 is biotransformed at
      very low rates to hexafluoroacetone trihydrate but irreversible binding of
      hexafluoroacetone trihydrate cannot be demonstrated, even with the application of
      very sensitive methods, and is considered unlikely, based on the combination of
      the results obtained.

PMID- 8869828
TI  - Pharmacokinetics of ethylene glycol. I. Plasma disposition after single
      intravenous, peroral, or percutaneous doses in female Sprague-Dawley rats and CD
      1 mice.
AB  - The pharmacokinetics of [1,2-14C]ethylene glycol (EG) were evaluated in female
      Sprague-Dawley rats and CD-1 mice to characterize the plasma disposition after
      intravenous (IV), peroral (PO), and percutaneous (PC) doses. Rats were given
      doses of 10 or 1000 mg/kg by each route, and additional PO doses of 400, 600, or
      800 mg/kg. Mice were also given IV and PO (bolus gavage) doses of 10 or 1000
      mg/kg, and additional PO doses of 100, 200, or 400 mg/kg. PC doses in mice were
      100 or 1000 mg/kg, and both species were given a 1000 mg/kg PC dose with a 50%
      (w/w) aqueous solution (2 ml/kg) to simulate antifreeze exposure. Results from
      this study have shown that orally-administered EG is very rapidly and almost
      completely absorbed in both rats and mice, with a bioavailable fraction of 92
      100% in rats and similar percentages at the higher doses in mice. In contrast,
      the absorption of cutaneously applied EG is comparatively slow in both species. A
      species difference in the overall absorption of PC doses was demonstrated, with
      higher recoveries of 14C observed after PC doses in mice than for rats and a
      greater penetration of 14C after applying a 50% aqueous PC dose in mice than in
      rats, as evidenced by quantifiable plasma 14C concentrations only in mice. The
      major metabolites in both rats and mice are CO2 and glycolate. Oxidative
      metabolic pathways are saturated at high PO doses in both species, resulting in a
      shift from exhaled CO2 as the major excretion route to urinary excretion. The
      capacity to metabolize more completely EG to CO2 at low doses seems to be greater
      in the mouse than in the rat, as evidenced by the absence of urinary oxalate from
      EG-dosed female mice, and saturation of metabolic pathways at a comparatively
      lower dose in mice than for rats. This evidence suggests that dose-dependent
      changes in EG excretion in female Sprague-Dawley rats and CD-1 mice probably
      resulted from capacity-limited effects on EG metabolic pathways for the
      production of CO2 and a compensatory urine clearance of glycolate. Results from
      the present study corroborate previous observations in rats for the lower doses,
      but demonstrate a substantial difference in single-dose pharmacokinetics for IV
      and PO 1000 mg/kg doses in mice vs. rats. In summary, these data indicate that
      mice show a nonlinear plasma disposition of total radioactivity (EG and its
      metabolites) as dose is increased, whereas in rats plasma kinetics were linear
      over the dose range evaluated, whereas excretion kinetic patterns were nonlinear
      in both species as dose is increased.

PMID- 8869829
TI  - Local perivascular administration of basic fibroblast growth factor: drug
      delivery and toxicological evaluation.

PMID- 8869830
TI  - Pathophysiology and treatment of hepatitis C.
AB  - Hepatitis C virus (HCV) infection is associated with a variable disease course
      and response to therapy. Some infected patients may develop little or no disease
      for 30 to 40 years, whereas others will develop cirrhosis within 5 to 10 years.
      Both host and viral factors influence the rate of disease progression. The
      management of patients is determined by the severity of their disease assessed by
      liver biopsy. Those with mild hepatitis without fibrosis do not require treatment
      but should undergo liver biopsy every 3 years. Patients with mild hepatitis with
      fibrosis, or with moderate or severe hepatitis with or without fibrosis, should
      be offered treatment. Interferon-alpha (IFN alpha) is currently the only licensed
      treatment for HCV infection. Although initial response rates to IFN alpha are
      high, over half the patients relapse and a sustained response is achieved in only
      10 to 35% of patients. Higher doses of IFN alpha and a longer treatment duration
      are associated with better response rates. Treatment options for those who fail
      to respond to IFN alpha include a second course of IFN alpha at a higher dose or
      IFN alpha in combination with ribavirin, phlebotomy or ursodeoxycholic acid. At
      present, however, there are insufficient data to routinely recommend any of these
      options.

PMID- 8869831
TI  - The inflammatory cytokines. New developments in the pathophysiology and treatment
      of septic shock.
AB  - Bacterial products [lipopolysaccharide (LPS) with Gram-negative bacteria and
      toxins, superantigens or cell wall fragments with Gram-positive bacteria] are the
      main activators of the septic shock cascade. These molecules interact with
      monocytes, macrophages and endothelial cells to produce inflammatory cytokines
      [tumour necrosis factor (TNF) and interleukins 1 and 6], and may activate other
      harmful pathways such as the coagulation system, complement cascade and lipid
      mediators. As a therapeutic strategy, antibodies directed against LPS have been
      well studied, although, on the whole, the clinical results have been
      disappointing. Other possible interventions that have not yet been tested
      clinically include natural intracellular antibacterial proteins (e.g. bacterial
      permeability-increasing protein) and high density lipoprotein (responsible for
      detoxifying LPS in the body). The stimulation pathway of responsive cells by
      bacterial products is also another possible target for intervention. Compounds
      under investigation include soluble CD14 and antibodies directed against CD14 or
      LPS binding protein. Antibodies directed against the cytokines are another
      option. Anti-TNF antibodies are currently being investigated, but conclusive
      evidence of their activity is still lacking. Soluble receptors (e.g. interleukin
      1 receptor antagonist, or soluble TNF receptor) are another possibility; one
      soluble TNF receptor is still undergoing clinical investigation.

PMID- 8869833
TI  - Fluoroquinolones in urinary tract infections. Proper and improper use.

PMID- 8869832
TI  - Interleukin-12: potential clinical applications in the treatment and prevention
      of infectious diseases.
AB  - Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity by
      facilitating type 1 helper T-lymphocyte responses, enhancing the lytic activity
      of natural killer cells, augmenting specific cytolytic T-lymphocyte responses,
      and inducing the secretion of interferon-gamma. It can also boost the production
      of some subclasses of IgG antibodies. IL-12 has demonstrated activity in several
      mouse models of infectious diseases caused by viruses, protozoans, fungi, and
      mycobacteria. It has the potential for use either as a single immunotherapeutic
      agent, in combination with chemotherapeutic agents, or as a vaccine adjuvant.
      Endogenous IL-12 appears to play an important role in the host defence against
      intracellular pathogens; poor IL-12 production observed in mononuclear cells from
      patients infected with the human immunodeficiency virus may be involved in the
      susceptibility of this patient group to opportunistic infections. Clinical trials
      are being initiated to evaluate the possible therapeutic uses of IL-12.

PMID- 8869834
TI  - The appropriate use of quinolones.

PMID- 8869835
TI  - Epidemiology, control and treatment of multiresistant pneumococci.

PMID- 8869837
TI  - Epidemiology, control and treatment of methicillin-resistant Staphylococcus
      aureus.

PMID- 8869836
TI  - Epidemiology and control of multiresistant enterococci.

PMID- 8869838
TI  - Chronic obstructive pulmonary disease. Mortality and mortality reduction.
AB  - Chronic obstructive pulmonary disease (COPD) affects an estimated 15 million
      Americans and is the fourth most common cause of death in the US. Despite an
      improved understanding of the disease, treatment has changed little over the past
      20 to 30 years and COPD remains a major health problem worldwide. Smoking is the
      major risk factor for COPD, accounting for some 90% of cases. Therefore, smoking
      cessation remains the most important intervention. Other available
      pharmacotherapeutic options include corticosteroids, bronchodilators, antibiotics
      for the treatment of acute exacerbations, mucokinetic agents, and oxygen for the
      advanced stages of the disease. Recent data investigating the use of dornase alfa
      (recombinant human deoxyribonuclease I) in patients with acute exacerbations of
      COPD were disappointing and failed to demonstrate a mortality benefit. While it
      is likely that ongoing research will optimise the use of older agents and
      identify new treatment options for patients with COPD, smoking cessation will
      probably remain the most important intervention and should be a key focus of
      future initiatives aimed at controlling this disease.

PMID- 8869840
TI  - The challenge of changing healthcare systems.
AB  - Healthcare systems are in flux throughout the world. Traditional structures and
      attitudes are changing. The balance of power between political bodies, payers,
      providers and patients is being destabilised. New approaches by governments and
      forward integration by drug companies and payers into care management are all
      major changes from the past. In the future, healthcare providers, particularly
      hospitals, will have to complement medical with business skills to survive in a
      more competitive environment. Experience shows that there is major potential for
      improvement in terms of radical rethinking of how care is provided (e.g. at least
      a 30% reduction in hospital days per insured life together with quality-of-care
      improvements). In particular, the economic value of changes in treatment (e.g.
      ambulatory surgery, switch to home therapy) should be understood and optimised.
      In a new world scenario, payers and providers will shape the healthcare
      environment by introducing novel approaches and integrating healthcare delivery.
      This process, coupled with the introduction of new approaches to competition and
      risk sharing by the government, could cause the emergency of high performance and
      more cost-effective healthcare systems.

PMID- 8869839
TI  - New concepts in the pathophysiology and management of middle ear disease in
      childhood.
AB  - Middle ear disease encompasses acute otitis media, recurrent otitis media, and
      otitis media with effusion. For many children, middle ear disease occurs early in
      life, is chronic and recurrent and can impair language development and/or school
      performance. Risk factors for recurrent otitis media include early disease onset,
      bottle feeding, daycare attendance, exposure to cigarette smoke and immunological
      defects or immaturity. Antimicrobial therapy in acute otitis media is associated
      with earlier resolution and a reduction in the frequency of persistent disease
      and suppurative complications. An antimicrobial agent should be selected
      according to its activity, tolerability and concentrations achieved in the middle
      ear. At present, amoxicillin remains the drug of choice for acute otitis media.
      Antimicrobial prophylaxis is also effective, but only for the duration of
      therapy. Future challenges for the management of middle ear disease include the
      treatment of penicillin-resistant Streptococcus pneumoniae, effective prevention
      of relapses, and the development of a vaccine for S. pneumoniae that has the
      appropriate serotypes and is immunogenic in young children.

PMID- 8869841
TI  - Antibiotic usage: policy, clinical and pharmacoeconomic outcomes.

PMID- 8869842
TI  - Antibiotic usage: pharmacoeconomic impact in a changing healthcare system.
AB  - There is limited experience in the healthcare field in terms of the evaluation of
      treatment costs. All too often, healthcare providers focus on the financial end
      points (such as drug acquisition costs) as opposed to clinical end-points. This
      approach fails to view products from a broader perspective and tends to ignore
      the impact of a drug in terms of better patient compliance, fewer office visits,
      reduced length of hospital stay, or avoidance of hospitalisation. This article
      will briefly discuss the techniques used in the US to improve the utilisation of
      antibiotics, and describe the move towards the use of outpatient (i.e. outpatient
      care attached to a hospital, or in an infusion or clinic setting) or home
      therapy.

PMID- 8869843
TI  - Antibiotic policies. Economics and effectiveness from a UK perspective.

PMID- 8869844
TI  - Use of antimicrobials in Swiss hospitals. Swiss Committee of Anti-Infective
      Agents.

PMID- 8869845
TI  - Epidemiology, control and treatment of multiresistant gram-negative rods.

PMID- 8869846
TI  - Epidemiology, control and treatment of multidrug-resistant tuberculosis.

PMID- 8869847
TI  - The calcium antagonist controversy; implications beyond drug prescription.

PMID- 8869848
TI  - Platelet activation and coronary interventions.

PMID- 8869849
TI  - Dual sensor pacing technology.

PMID- 8869850
TI  - Assessing coronary stenosis: by which method and for what purpose?

PMID- 8869851
TI  - The athlete's heart revisited.

PMID- 8869852
TI  - CABG v PTCA in multi-vessel disease: angiographic insights.

PMID- 8869853
TI  - The unnecessary controversy.

PMID- 8869854
TI  - Nifedipine in acute coronary syndromes: Furberg's refrain revisited.

PMID- 8869855
TI  - Critical appraisal of recent studies on nifedipine and other calcium channel
      blockers in coronary artery disease and hypertension.

PMID- 8869856
TI  - Phosphorus magnetic resonance spectroscopy of the human heart: current status and
      clinical implications.

PMID- 8869857
TI  - Assessing coronary stenosis. Quantitative coronary angiography versus visual
      estimation from cine-film or pharmacological stress perfusion images.
AB  - Visual judgment of stenosis severity from cine-film or single-photon emission
      computed tomographic dipyridamole perfusion images was compared to assessment of
      stenosis severity as measured with digital quantitative coronary angiography.
      Thirty patients with angiographically verified single-vessel disease underwent
      dipyridamole thallium stress testing within 90 days of angiography. RESULTS: A
      percent diameter stenosis of > or = 50%, a percent area stenosis of > or = 75%,
      and a stenotic flow reserve of < 3.75 measured by quantitative coronary
      angiography (CMS, version 1.1, Medis Inc.) corresponded to haemodynamically
      significant stenosis as evaluated by visual estimates from cine-film or perfusion
      images. Quantitative coronary angiography percent diameter stenosis (51.2% +/-
      12.6%) correlated closely (r = 0.74) but underestimated significantly visual
      assessment of stenosis severity from cine-film (69.3% +/- 21.2%; P = 0.0001).
      However, quantitative coronary angiography percent area stenosis (74.7% +/-
      11.7%) more closely reflected visual estimates from cine-film (P = 0.19).
      Quantitative coronary angiography stenotic flow reserve showed the highest
      positive and negative predictive value regarding visual estimates from cine-film
      (88%, 86%) or perfusion images (88%, 64%) followed by percent diameter stenosis
      (86%, 75% 86%, 56%) and percent area stenosis (87%, 80%, 87%, 60%), respectively.
      CONCLUSION: Evaluation of coronary lesions by quantitative coronary angiography
      corresponds closely with visual estimates from cine-film and haemodynamic
      significance as evaluated by dipyridamole perfusion images.

PMID- 8869858
TI  - Failure to demonstrate myocardial ischaemia in patients with angina and normal
      coronary arteries. Evaluation by continuous coronary sinus pH monitoring and
      lactate metabolism.
AB  - BACKGROUND: Whether myocardial ischaemia is the mechanism underlying chest pain
      in patients with angina and normal coronary arteriograms is controversial. We
      sought to detect the presence of transient myocardial ischaemia using continuous
      monitoring of coronary sinus blood pH during atrial pacing. METHODS AND RESULTS:
      We studied 14 patients (eight women, six men, mean age 51 +/- 3 years) with
      typical exertional angina and normal coronary arteriograms and nine patients with
      coronary artery disease (two men, seven women, mean age 61 +/- 7 years). Of the
      14 patients with normal coronary arteries, eight had a reduced coronary blood
      flow reserve (< 2.5-fold increase), 11 had an ischaemic-appearing response to
      exercise testing, six had reversible perfusion detects on exercise thallium scans
      and one had resting left bundle branch block. All patients underwent continuous
      pH monitoring of coronary sinus blood at rest and during incremental atrial
      pacing (up to 160 bpm). Coronary sinus oxygen saturation and myocardial lactate
      extraction ratio were also evaluated at rest and at peak pacing. Eleven patients
      with angina and normal coronary arteries and eight with coronary artery disease
      had angina during pacing. Both patients with angina and normal coronary arteries
      (n = 13) and patients with coronary artery disease (n = 9) showed a fall in
      coronary sinus pH (-0.02 +/- 0.02 vs -0.11 +/- 0.03 pH units, respectively, P <
      0.01). Coronary sinus oxygen saturation expressed as a percentage dropped by 19
      +/- 6% in patients with coronary artery disease and by 6 +/- 2% in patients with
      angina and normal coronary arteriograms (P < 0.05). Myocardial lactate extraction
      ratio decreased from 33 +/- 6% to -1.4 +/- 4% in patients with coronary artery
      disease and from 23 +/- 8% to 20 +/- 8% in those with angina and normal coronary
      arteriograms. Three patients with angina and normal coronary arteries had a drop
      in coronary sinus pH > 0.02 pH units (-0.043 +/- 0.006 pH units) and in coronary
      sinus oxygen saturation > 8% (16 +/- 3%) consistent with myocardial ischaemia.
      CONCLUSION: Despite severe chest pain and reduced coronary flow reserve after
      pacing, most patients with angina and normal coronary arteriograms do not show
      metabolic evidence of myocardial ischaemia.

PMID- 8869859
TI  - Early diagnosis of acute myocardial infarction using clinical and
      electrocardiographic data at presentation: derivation and evaluation of logistic
      regression models.
AB  - The aim of this study was to determine which, and how many, data items are
      required to construct a decision support algorithm for early diagnosis of acute
      myocardial infarction using clinical and electrocardiographic data available at
      presentation. Logistic regression models were derived using data items from 600
      consecutive patients at one centre (Edinburgh), then tested prospectively on 510
      cases from the same centre and 662 consecutive cases from another centre
      (Sheffield). Although performance of the models increased with progressive
      addition of data inputs when applied to training data, a simple six-factor model
      was the most effective on test data, yielding accuracies of 84.3 and 83.6% on the
      two test sets. A model constructed solely of electrocardiographic data performed
      nearly as well as those incorporating clinical data. Previously published
      logistic regression models did not perform so well as the models derived from
      data collected for this study.

PMID- 8869860
TI  - Angiographic follow-up results of a randomized study on angioplasty versus bypass
      surgery (GABI trial). GABI Study Group.
AB  - Although several randomized trials have been performed to compare the outcomes of
      percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass
      surgery (CABG) in patients with multivessel disease, there is little data
      available on angiographic follow-up results. The present substudy of the German
      angioplasty versus bypass surgery investigation (GABI Trial) compares the
      angiographic revascularization status in these two cases 6 months after
      treatment. Follow-up angiograms were available in 102 CABG patients and 117 PTCA
      patients. Although the protocol excluded patients with total occlusion, on follow
      up 6 months after treatment we found total occlusion of 94 native arteries
      (36.9%) in the CABG group and of six arteries (2.5%) in the PTCA group (P <
      0.001). The rate of occluded native vessels did not correlate significantly with
      the severity of the lesion before bypass surgery. In the CABG group 31 bypass
      grafts (12.2%) were found to be occluded at the 6 month follow-up examination
      (29/225 vein grafts [12.9%]; 2/30 mammary artery grafts [6.7%]). The main
      pathway, defined as the nutrient vessel (native vessel or bypass graft) providing
      the least resistance to blood flow, was narrowed by a lesion with a diameter
      stenosis of 70-100% for 36 target lesions (14.1%) in the CABG group and 39 target
      lesions (16.2%) in the PTCA group (P, ns). However, the prevalence of moderately
      severe lesions with a 50-69% diameter reduction of the main pathway was
      significantly greater in the PTCA group (44 lesions, 18.3%) than in the CABG
      group (19 lesions, 7.5%, P < 0.01). Thus, 6 months after randomized allocation to
      PTCA or CABG, we found comparable rates of high-grade lesions in the main
      pathways of both treatment groups. Whereas moderately severe lesions of the main
      pathway were predominantly seen in the PTCA group, there was marked disease
      progression to total occlusion in the native circulation after bypass grafting.

PMID- 8869861
TI  - Long-term survival after myocardial infarction: relationship with thrombolysis
      and discharge medication. Results of the Augsburg Myocardial Infarction Follow-up
      Study 1985 to 1993.
AB  - A large number of randomized clinical trials have shown that thrombolysis, long
      term treatment with beta-blockers, antiplatelet drugs, and angiotensin converting
      enzyme inhibitors improve survival after acute myocardial infarction (AMI).
      However, for calcium channel blockers (nifedipine, diltiazem, and verapamil)
      there was either no benefit, or positive effects have been reported in subgroups
      only. Recent studies have raised concern about the safety of this drug class,
      especially in patients with coronary heart disease. We studied the long-term
      survival, for a median follow-up time of 4.4 years, of 1197 non-diabetic patients
      in the population-based AMI registry in Augsburg, Germany, aged 25-74 years, who
      had survived a first Q wave acute myocardial infarction for at least 28 days. The
      impact of thrombolysis and prescribed medication at discharge (beta-blockers,
      antiplatelet drugs, and calcium channel blockers) on long-term survival was
      analysed using the Cox-Proportional-Hazard model, controlling for age, sex, and
      concomitant cardiac drug use. Thrombolysis (risk ratio, RR, 0.72; 95% confidence
      interval, CI, 0.48-1.08), long-term beta-blockade (RR 0.52; 95% CI 0.36-0.74) and
      antiplatelet drug use (RR 0.69; 95% CI 0.50-0.94) were associated with
      considerable reductions in total mortality. The use of calcium channel blockers
      was not associated with a reduction in total mortality (RR 1.23; 95% CI 0.89
      1.69). Separate analyses for nifedipine (RR 1.00; 95% CI 0.68-1.48), and
      diltiazem (RR 1.55; 95% CI 1.04-2.32) showed an increased risk of death
      associated with the latter. Using patients on beta-blockers only (RR 1.00) as a
      reference, the prescription of these calcium channel blockers was consistently
      associated with an increased total mortality (nifedipine, without beta-blockers
      RR 1.20; 95% CI 1.12-3.57, diltiazem, without beta-blockers RR 2.87; 95% CI 1.75
      4.70). These results from an observational study demonstrate a benefit of
      thrombolysis, beta-adrenergic blockade and antiplatelet drug use on long-term
      survival in acute myocardial infarction patients. Calcium channel blocker use
      appears to be associated with an increased risk of death. These data support the
      need for controlled trials to address this issue specifically.

PMID- 8869863
TI  - PTCA: periprocedural platelet activation. Part II of the Duesseldorf PTCA
      platelet study (DPPS)
AB  - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) with its
      various manipulations could create a dangerous, sudden haemostatic response. This
      study was performed to investigate PTCA-induced periprocedural changes in
      platelet activation and its consequences. METHODS: Twenty-five consecutive
      patients admitted for elective PTCA were preclassified as having or not having
      circulating activated platelets. Blood samples were taken for platelet activation
      marker analysis before, six times during and 2 h after PTCA. Intravascular
      platelet activation was analysed by flow cytometry to measure activation
      dependent surface markers thrombospondin, P-selectin (CD62) and lysosomal GP53
      (CD63). RESULTS: PTCA was associated with a significant reduction of peripheral
      platelet count. The initiation of the PTCA procedure led to a significant loss of
      more than 50% of the degranulated, activated platelets. After PTCA, the number of
      degranulated, activated platelets uniformly increased. CONCLUSIONS: We conclude
      that PTCA can induce consumption, particularly of preactivated platelets, and
      lead to sustained platelet activation after the procedure. This might explain why
      preactivated patients are at increased risk of suffering periprocedural ischaemic
      events and why increased thrombogenicity favours acute flow disruption and the
      progression of coronary stenosis at the lesion site.

PMID- 8869862
TI  - Recombinant hirudin as a periprocedural antithrombotic in coronary angioplasty
      for unstable angina pectoris.
AB  - Percutaneous transluminal coronary angioplasty is often complicated by thrombotic
      abrupt vessel closure in patients with unstable angina pectoris. The present
      multicentre trial was performed to determine the feasibility of two-dose regimens
      of recombinant hirudin (r-hirudin) compared to standard heparin in patients
      undergoing coronary angioplasty for unstable angina, and to investigate the
      effects of the different treatment regimen on markers of coagulation activation.
      At five participating centres, 61 patients were randomly enrolled in one of two
      sequential groups of r-hirudin (group 1: 0.3 mg.kg-1 i.v. bolus, 0.12 mg.kg-1.h-1
      i.v. infusion; 21 patients; group 2: 0.5 mg.kg-1 i.v. bolus, 0.24 mg.kg-1.h-1
      i.v. infusion; 19 patients) or in a heparin control group (150 IU.kg-1 i.v.
      bolus, 20 IU.kg-1.h-1 i.v. infusion; 21 patients). Antithrombotic therapy was
      started immediately before coronary angioplasty and continued for 24 h. This was
      followed by a low-dose anticoagulant infusion for another 24 h (r-hirudin: 0.04
      mg . kg-1 . h-1; heparin: 7 IU . kg-1 . h-1). Activated partial thromboplastin
      time, r-hirudin plasma concentrations by both immunological and functional assay,
      thrombin-hirudin complex, thrombin-antithrombin III complex, soluble fibrin, and
      prothrombin fragment 1 + 2 were closely monitored. The median partial
      thromboplastin time prolongations at 24 h vs baseline were found to be 1.9-fold
      and 2.3-fold in r-hirudin group 1 and dose group 2, respectively, and 3.0-fold in
      the heparin group. There was a dose-dependent correlation between partial
      thromboplastin time and the r-hirudin plasma levels (r = 0.61). In five of 21
      patients of dose group 1, three of 19 patients of dose group 2, and 10/21
      patients of the heparin group, partial thromboplastin time values exceeding the
      predefined target range prompted an interruption of the infusion. One major
      bleeding complication occurred in dose group 2. The functional assay for the
      estimation of r-hirudin plasma concentrations showed excellent correlations to
      the immunological technique (r = 0.99). Differences between the thrombin-hirudin
      complex levels could not be observed. Increased concentrations of thrombin
      antithrombin III complex, soluble fibrin, and prothrombin fragment 1 + 2 were
      seen 4-8 h after coronary angioplasty and after reduction of the high-dose
      therapy in dose group 1 when compared with dose group 2 and the heparin group,
      respectively. Based on coagulation tests the present study showed the feasibility
      of a periprocedural antithrombotic regimen with r-hirudin for patients undergoing
      coronary angioplasty for unstable angina. In addition to the partial
      thromboplastin time the determination of r-hirudin plasma levels by a chromogenic
      substrate assay considerably improves the monitoring of therapy. The lower dose r
      hirudin regimen seems to be suboptimal as periprocedural anticoagulation in
      coronary angioplasty patients as indicated by markers of thrombin generation and
      thrombin activity.

PMID- 8869864
TI  - Effects of two different enalapril dosages on clinical, haemodynamic and
      neurohumoral response of patients with severe congestive heart failure.
AB  - Angiotensin converting enzyme inhibitors improve symptoms and prolong life in
      congestive heart failure, but the dose in the individual patient is uncertain. A
      randomized, 48-week, double-blind study was performed to investigate the safety
      and efficacy of 'high' in comparison to continued 'low' angiotensin converting
      enzyme inhibitor therapy in severe heart failure. Eighty-three patients (56 +/-
      1.1 years; 69 men, 14 women) in New York Heart Association functional class
      III/IV on digoxin, furosemide and 'low' angiotensin converting enzyme inhibitors
      (captopril < or = 50 mg.day-1 or enalapril < or = 10 mg.day-1) were included.
      After a > or = 14 day run-in on 10 mg.day-1 enalapril, digitalis and furosemide,
      right heart catheterization at rest and exercise was performed. All patients
      presented with atrial pressure > 10 mmHg and/or pulmonary artery pressure > 35
      mmHg, and/or cardiac index < 2.5 l.min-1.m-2 at rest. Patients then received
      enalapril 5 mg twice daily (n = 42), or 20 mg twice daily (n = 41) in random
      order. Thus, patients randomized to low doses of enalapril actually had no change
      in therapy from baseline to 48 weeks. Forty-three patients (52%) completed the
      study, 19 patients on the low dose and 24 patients on the high dose. Both dosages
      equally influenced survival with 15 (18%) deaths, eight on low dose and seven on
      high dose. After 48 weeks, functional capacity by New York Heart Association
      class improved more on the high dose than on the low dose (P = 0.04). In
      contrast, alterations in invasive haemodynamic variables at rest and exercise as
      well as maximal exercise capacity were comparable in both groups. Diastolic blood
      pressure decreased and the change between both groups was statistically
      significant (P = 0.01). Changes in plasma creatinine levels did not differ
      between high and low dose treatment and no patients had to be withdrawn because
      of deterioration in kidney function. With regard to neurohumoral activity, a
      tendency to a discrepant response to both treatments was observed with a blunted
      increase in noradrenaline on high versus low enalapril dose. Thus, high-dose
      enalapril treatment proved superior to low dose as regards symptomatology in
      severe heart failure after long-term treatment, despite similar effects on
      haemodynamics and on maximal exercise capacity.

PMID- 8869865
TI  - Prognostic value of posterior wall thickness in childhood dilated cardiomyopathy
      and myocarditis.
AB  - M-mode indices of left ventricular dimension and posterior wall thickness were
      derived from echocardiograms of children presenting with dilated
      cardiomyopathy/myocarditis and were related to outcome. Echocardiograms from 16
      of 18 children were manually digitized to obtain changes of left ventricular
      dimension and posterior wall thickness throughout the cardiac cycle. Indices of
      ventricular function and the ratio of end-diastolic posterior wall thickness to
      cavity dimensions were obtained. Patients were divided into group I (alive, n =
      7), and group II (died, n = 6 or heart transplantation, n = 3) at median follow
      up of 25 months. No significant difference was seen for the shortening fraction,
      the percentage of posterior wall thickening or the normalized peak rate of left
      ventricular filling. The normalized peak rate of posterior wall thinning was
      greater in group II. The posterior wall thickness to cavity dimension ratio was
      higher in group I (median = 0.19) than group II (median = 0.13) (P < 0.005). Five
      of six survivors, whose ventricular function improved, had ratios > 0.17. All but
      one with a ratio < or = 0.16 remained with a dilated heart, died or required
      transplantation (P = < 0.01). A relatively thicker posterior wall (ratio > 0.17)
      was associated with better prognosis and recovery. This index should be taken
      into account in decision-making regarding timing for cardiac transplantation.

PMID- 8869866
TI  - Histological abnormalities of muscle from limb, thorax and diaphragm in chronic
      heart failure.
AB  - The aim of the study was to compare histological findings in limb and respiratory
      muscles from control subjects and patients with heart failure of two different
      aetiologies. Biopsies of the quadriceps femoris, strap, diaphragm and pectoralis
      major muscles were taken from each group. The control subjects all had normal
      left ventricular function, and comprised seven undergoing surgical ablation of
      electrical pathways and 10 undergoing coronary artery surgery. The heart failure
      group had severely impaired left ventricular function, and were undergoing
      cardiac transplantation in all except one case. Ten patients with idiopathic
      dilated cardiomyopathy and seven with heart failure of ischaemic origin were
      studied. Conventional histochemical techniques and specific anti-myosin
      immunofluorescent stains were used. There were no consistent differences in fibre
      type prevalence or diameter between the groups. There were no important
      histological abnormalities in the two control groups. There were minor/major
      changes in four of seven patients with ischaemic heart failure but no major
      abnormality, whilst in the dilated cardiomyopathy group there were five of 10
      patients with minor/major changes and three of 10 with major abnormalities (P <
      0.001 vs controls). A variety of changes were seen in both groups of heart
      failure subjects. These were more marked in the dilated cardiomyopathy than
      ischaemic group, and suggest the presence of fibre type regeneration and/or
      transformation. Amongst the findings were tubular aggregates, internalization of
      nuclei, bizzare staining of myosin and staining of neonatal myosin (seven of 14)
      and the presence of cores (five of 14). Such changes were more prominent in the
      diaphragm than in the other muscles. In conclusion, histological abnormalities
      are present in the limb and respiratory muscles from subjects with heart failure.
      The changes are most marked in subjects with idiopathic dilated cardiomyopathy,
      suggesting that there may be a generalized cardiac and skeletal myopathy in these
      subjects. The presence of histological abnormalities in the respiratory muscles
      may contribute to the pathogenesis of dyspnoea in heart failure.

PMID- 8869867
TI  - Initial experience with dual-sensor rate-responsive pacemakers in children.
AB  - The efficacy of a new single-chamber, rate-responsive pacemaker that utilizes
      information from two sensors, activity and stimulus to T wave, was evaluated in
      15 children during a mean follow-up period of 10.3 +/- 3.3 months (range 5-16
      months). There were 10 males and five females, with a mean age of 5.9 +/- 3.8
      years (range 9 months-16 years). The indication for pacing was high grade
      atrioventricular block in 10 (eight postoperative, two congenital), and sinus
      node dysfunction in five patients. In endocardial implants the mean T wave
      amplitude was 2.48 +/- 0.7 mV, and mean T wave sensing 91 +/- 6.3%, whereas in
      epicardial implants T wave amplitude and sensing were inadequate. Each patient
      underwent 24-h Holter monitoring and 10 performed a graded treadmill test in
      three sensor-blending modes (Stimulus-T = Activity, Stimulus-T > Activity,
      Stimulus-T < Activity), using the chronotropic assessment exercise protocol.
      Sensor cross-checking was analysed by continuous tapping over the pacemaker.
      Holter monitoring demonstrated that pacing rate variations were closely related
      to daily activity. At the initial phases of exercise testing, the mean percentage
      of increase in pacing rate was significantly lower in Stimulus-T > Activity mode,
      when compared to Stimulus-T = Activity (P < 0.01); however, the initial disparity
      among the three modes disappeared halfway through the exercise and similar heart
      rate changes were observed thereafter. Continuous tapping over the pacemaker in
      Stimulus-T = Activity mode caused an initial increase in pacing rate, and
      inappropriate responses were quickly corrected by sensor cross-checking. Rate
      modulation with a single-chamber, dual-sensor pacemaker is adequate and safe in
      children, and may offer significant advantages over single-sensor devices in
      endocardial implants.

PMID- 8869868
TI  - Influence of the mechanism of regurgitation on the quantification of mitral
      regurgitation by the proximal flow convergence method and the jet area method.
AB  - In 84 patients mitral regurgitation was quantified by angiography. The mechanism
      of regurgitation was determined by echocardiography (organic, n = 54, functional,
      n = 30). The radii of the proximal isovelocity surface areas in the flow
      convergence region for 28 and 41 cm.s-1 blood flow velocity and the area and
      length of the regurgitant jet were measured using colour flow Doppler imaging.
      The radii of the proximal isovelocity surface areas correlated more closely with
      the angiographic grade than the jet parameters irrespective of the mechanism of
      regurgitation. In more than 90% of the patients, grades I-II mitral regurgitation
      were correctly differentiated from grades III-IV by means of the radii of the
      proximal isovelocity surface areas. Using the jet parameters, the differentiation
      was correct in 50-90% of the patients depending on the mechanism of
      regurgitation. The jet area method particularly failed to identify grades III-IV
      organic mitral regurgitation due to a high prevalence of eccentric jets in these
      patients. It is concluded that the proximal flow convergence method was suitable
      for the quantification of mitral regurgitation irrespective of the mechanism of
      mitral regurgitation. On the other hand, the value of the jet area method
      depended largely on the regurgitation mechanism.

PMID- 8869869
TI  - Fifteen year surveillance of echinococcal heart disease from a referral hospital
      in Greece.
AB  - Ten cases of hydatid heart disease were treated over a 15-year period (1980
      1995). Cysts were located in the left ventricular wall (four patients), right
      ventricular wall (one patient), interventricular septum (one patient),
      interatrial septum (one patient), right atrium (one patient), pericardial cavity
      (one patient) and in multiple loci (one patient). Apart from two asymptomatic
      cases, clinical manifestations included chest pain (four patients), anaphylactic
      shock (one patient), constrictive pericarditis (one patient), congestive heart
      failure (one patient) and arterial embolism (one patient). Computed tomography
      was found useful in the detection of hydatid cysts and also in the determination
      of their morphology. Magnetic resonance was performed in three patients, with
      satisfactory imaging. Three out of the 10 patients died: rupture of pulmonary
      echinococcal cyst (one patient), massive pulmonary hydatid embolism (one patient)
      and rupture of an undiagnosed hydatid cyst of the right atrium during cannulation
      for cardiopulmonary bypass (one patient). One other patient experienced recurrent
      systemic embolism and became hemiplegic. Six patients were successfully treated.
      In five patients, the cysts were excised by open heart surgery, while in one by
      pericardiectomy. In addition, antiparasitic drugs were successfully used in two
      patients with long-term satisfactory results. In conclusion, cardiac
      echinococcosis is associated with an increased risk of potentially lethal
      complications. Newer techniques of cardiac imaging have helped locate the cysts
      while surgical removal may offer cure. Some patients responded to specific long
      term drug treatment.

PMID- 8869870
TI  - Cardiac anatomy, function and metabolism in elite cyclists assessed by magnetic
      resonance imaging and spectroscopy.
AB  - We investigated whether left ventricular hypertrophy in elite cyclists is
      associated with functional changes or abnormal energy metabolism. Left
      ventricular hypertrophy is a powerful risk factor for sudden cardiac death with
      different prognostic significance among the various geometric forms. Cyclists may
      have a combination of mixed eccentric and concentric hypertrophy. Magnetic
      resonance imaging was used to define left ventricular mass, geometry and
      function. Thirteen highly trained male cyclists and 12 healthy controls were
      investigated. Proton-decoupled phosphorus-31 cardiac spectroscopy was performed
      to assess parameters of myocardial high-energy phosphate metabolism. Left
      ventricular mass and end-diastolic volumes normalized for body surface area were
      significantly higher in cyclists (124.1 +/- 9.4 g.m-2 and 106.2 +/- 11.4 ml.m-2,
      respectively) than in controls (85.9 +/- 9.3 g.m-2 and 79.1 +/- 11.6 ml.m-2,
      respectively), (both P < 0.0001). The left ventricular mass to end-diastolic
      volume ratio, as a parameter of left ventricular geometry, was not significantly
      increased in cyclists compared to controls. Resting left ventricular ejection
      fraction, cardiac index, and systolic wall stress in cyclists did not differ
      significantly from those of controls. The phosphocreatine to adenosine
      triphosphate ratio was not significantly different between cyclists and controls
      (2.2 +/- 0.34 vs 2.2 +/- 0.17, ns). Cyclists show prominent left ventricular
      hypertrophy with normal geometry. The finding that the hypertrophic hearts of the
      cyclists had normal left ventricular function and a normal phosphocreatine to
      adenosine triphosphate ratio suggests that sport-induced left ventricular
      hypertrophy is a physiological adaptation rather than a pathophysiological
      response.

PMID- 8869871
TI  - Left ventricular volume calculations using a multiplanar transoesophageal
      echoprobe; in vitro validation and comparison with biplane angiography.
AB  - BACKGROUND: Biplane angiographic and transthoracic echocardiographic volume
      calculations have shown to be sufficiently reliable in symmetric hearts; however,
      they are unreliable in the presence of aneurysmatic distortions. Multiplane
      transoesophageal echocardiography offers unobstructed cross-sectional views of
      the heart from one stable transducer position with the potential of imaging
      irregular cavity forms more accurately. It was the purpose of this in vitro study
      to compare the precision of multiplanar transoesophageal echocardiography to that
      of biplane angiography in determining left ventricular volumes, especially in
      aneurysmatic models. METHODS: Seven silicon rubber models of the left ventricle
      from post-mortem specimens (four with aneurysms) were filled with 30 different
      volumes (range 153-256 ml, 197 +/- 30 ml). Echocardiographic cross-sections (20
      degree rotational steps) were obtained from different transducer positions,
      utilizing a multiplanar probe with a central rotational axis. Volumes were
      calculated using the disc-summation method. For comparison the same volumes were
      determined by standard biplane angiography. The minimum number of echo cross
      section necessary to optimize precision was analysed by calculating volumes for
      each increasing equidistant rotational step. RESULTS: Linear correlation between
      measured volume using a multiplanar transoesophageal echoprobe and true volume
      was high (r = 0.97) and significantly better than for biplane angiography (r =
      0.88; P < 0.001). Measurement bias and imprecision were also significantly lower
      with multiplanar echocardiography than with biplane angiography (3.9 +/- 7.1% vs
      11.1 +/- 15.4%, and 2.0 +/- 3.7% vs 5.9 +/- 8.3%; P < 0.001). Precision of
      biplane angiographic volume measurements was significantly influenced by the
      presence of aneurysmatic distortions. Multiplanar echo volumes, however, were not
      influenced by left ventricular geometry and transducer positions. Nine echo cross
      sections provided optimal precision. CONCLUSIONS: Three-dimensional
      echocardiographic volume calculations using a multiplanar transoesophageal
      echoprobe and the disc-summation method provide precise measurements unaffected
      by left ventricular geometry and transducer position in an in vitro setting.
      Standard biplane angiography is significantly less precise.

PMID- 8869872
TI  - Chagas' disease may also be encountered in Europe.

PMID- 8869873
TI  - Large left atrial thrombus mimicking atrial myxoma: successful treatment with
      anticoagulant therapy.

PMID- 8869874
TI  - Lipomatous hypertrophy of the atrial septum: complementary diagnosis by
      transoesophageal echocardiography and nuclear magnetic resonance imaging.

PMID- 8869875
TI  - Risk factors for cardiovascular disease in women: assessment and management.
AB  - Coronary heart disease (CHD) is the most important cause of death and disability
      among older women. A 50-year-old woman has a 46% risk of having CHD and a 31%
      risk of dying from it. Female CHD patients have a distinct clinical presentation,
      which includes more severe thromboembolic disease without coronary
      arteriosclerosis. Syndrome X also appears to be more prevalent in women.
      Oestrogen deficiency may be a trigger for this syndrome. The magnitude of the
      effect of various risk factors may also differ between women and men. In
      addition, there are risk factors unique to women. Lipid profiles differ between
      men and women. After menopause, the lipid profile changes unfavourably, with
      increasing levels of LDL cholesterol and decreasing levels of HDL cholesterol.
      Cigarette smoking, hypertension, diabetes mellitus, and obesity are all
      recognised risk factors for CHD in women. It is important to recognise that risk
      factors for CHD differ between men and women. Advising women to quit cigarette
      smoking, avoid obesity, increase physical activity, and prevent and treat
      hypertension and hyperlipidaemia will result in a reduction in CHD risk.
      Additional studies are needed to further contribute to our understanding of the
      complex risk factors underlying the development of CHD in women.

PMID- 8869876
TI  - Evidence for primary and secondary prevention of coronary artery disease in women
      taking oestrogen replacement therapy.
AB  - The increasing use of oestrogen replacement therapy in women has focussed
      attention on the cardioprotective properties it has demonstrated. Historically,
      it has been shown that women enjoy a certain protection from heart disease, a
      phenomenon, however, which has not been studied extensively. Women at every age
      have less coronary artery disease (CAD) than men, even when various risk factors
      are accounted for, although the presence of diabetes carries equal mortality for
      both sexes. However, women who do develop CAD have a greater risk of mortality
      than men with CAD. Other gender differences include a later age of onset of CAD
      for women, and a difference in the type of atherosclerotic lesions developed.
      Most striking is the fact that, in women, high-density lipoprotein (HDL) seems to
      be a more potent predictor of major cardiovascular events than low-density
      lipoprotein (LDL), or total cholesterol. The Postmenopausal Oestrogen and
      Progesterone Interventions (PEPI) Trial looked at changes in HDL, fibrinogen,
      blood pressure and serum insulin resulting from oestrogen use. Four regimens were
      compared against placebo in 875 women. The results showed that HDL was increased
      significantly, LDL decreased significantly, fibrinogen levels decreased
      significantly, and blood pressure and serum insulin levels were essentially
      unaffected by oestrogen and oestrogen/progestin interactions. The Heart and
      Oestrogen/Progestin Replacement (HERS) Study, currently underway, is a secondary
      prevention trial testing the protective effect of hormone therapy in women with
      documented CAD. This trial may definitively answer the question of whether
      hormones protect against CAD. After HERS, it may be unethical to continue
      conducting placebo-controlled trials in a therapy that has such documented
      cardioprotective benefit.

PMID- 8869877
TI  - Cardioprotective effects of ovarian hormones.
AB  - This paper reviews the evidence regarding the cardioprotective effects of
      oestrogen replacement therapy in postmenopausal women. Oestrogens have been shown
      to improve serum lipid profiles, carbohydrate metabolism, and insulin
      sensitivity; prevent the formation and development of atherosclerotic plaque;
      reduce blood pressure and plasma fibrinogen levels; and favourably affect overall
      cardiac function. Thus, oestrogen replacement therapy may prevent or inhibit the
      progression of existing coronary disease, and may also have a protective effect
      against acute cardiovascular and cerebrovascular ischaemic events.

PMID- 8869878
TI  - Physiological effects of ovarian hormones: clinical aspects and compliance.
AB  - Menopause is marked by the permanent cessation of menstrual bleeding. Deprivation
      of ovarian hormones due to decreasing ovarian activity causes widespread
      physiological effects. Disturbances in menstrual pattern and hot flashes are
      major reasons for hormone replacement therapy (HRT), but prevention of
      osteoporosis and cardiovascular disease are other considerations. Despite the
      large number of different hormone treatment regimens available, such problems as
      continued bleeding and concern about side effects engenders low compliance. To
      enhance compliance, it is important to ensure that post-menopausal women and
      their physicians are aware of the probable risks and benefits of hormone therapy
      before deciding whether or not to use preventive HRT.

PMID- 8869879
TI  - Oestrogen as a calcium channel blocker.
AB  - This paper reviews the evidence for calcium-antagonist properties of oestrogen
      which may offer long-term protective effects on the cardiovascular system in
      postmenopausal women. Oestrogen has already been shown to have a beneficial
      effect on cholesterol metabolism and deposition, thereby inhibiting the formation
      of atherosclerotic plaque and coronary atheroma. Calcium antagonism, resulting in
      both acute and chronic modulation of coronary and peripheral vasomotion, is
      another mechanism by which oestrogens may provide cardiovascular benefits to
      women, including those with existing cardiovascular disease.

PMID- 8869880
TI  - Practical aspects of preventing and managing athersclerotic disease in post
      menopausal women.
AB  - Factors that exacerbate the risk of atherosclerotic plaque formation include
      cigarette smoking, hypertension, hypercholesterolaemia, sedentary lifestyle, and
      oestrogen deficiency. The potentially important role of oestrogen deficiency in
      this process is evidenced by the significant increase in cardiovascular risk
      observed in women after menopause, and in the marked reduction in cardiovascular
      events observed in women who take hormone replacement therapy. Oestrogen
      replacement therapy, through an effect on the blood vessel wall and on serum
      lipids, also appears to stabilize existing atherosclerotic plaques. The
      combination of oestrogen and progesterone reduces risk of endometrial cancer
      while possibly delivering the same benefits as oestrogen alone. Other measures,
      such as antithrombotic therapy, exercise, and smoking cessation, also contribute
      to reduced risk of cardiovascular disease in older women.

PMID- 8869882
TI  - Specificity of two lipoxygenases from rice: unusual regiospecificity of a
      lipoxygenase isoenzyme.
AB  - The regio- and stereospecificity of two lipoxygenases from rice were investigated
      using arachidonic acid as the substrate. Rice seed lipoxygenase-2 (RSL-2)
      catalyzed oxygenation of arachidonic acid into a mixture of 5(S)-hydroperoxy
      6,8,11,14-eicosatetraenoic acid [5(S)-HPETE] and 15(S)-hydroperoxy-5,8,11,13
      eicosatetraenoic acid [15(S)-HPETE]. In addition, two double dioxygenase
      products, 5(S), 15(S)-dihydroperoxy-6,8,11,13 -eicosatetraenoic acid and
      8(S),15(S)-dihydroperoxy-5,9,11,13 -eicosatetraenoic acid, were obtained in a
      lower yield. The regiospecificity of the RSL-2-catalyzed oxygenation was pH
      dependent. Thus, incubation at pH 6.7 led to the formation of 5(S)-HPETE and
      15(S)-HPETE in a ratio of 52:48, and incubation at pH 9.8 strongly suppressed
      production of 5(S)-HPETE and led to formation of 5(S)-HPETE and 15(S)-HPETE in a
      ratio of 3:97. A pH-dependent orientation of arachidonic acid at the active site
      is proposed to explain these findings. Rice leaf pathogen-inducible lipoxygenase
      [Peng, Y.-L., Shirano, Y., Ohta, H., Hibino, T., Tanaka, K., and Shibata, D.
      (1994) J. Biol. Chem. 269, 3755-3761] catalyzed oxygenation of arachidonic acid
      into a single hydroperoxide isomer of high optical purity, i.e., 15(S)-HPETE
      (99.5% S).

PMID- 8869881
TI  - Phosphatidate phosphatases of mammals, yeast, and higher plants.
AB  - Phosphatidate phosphatase (EC 3.1.3.4) catalyzes the hydrolysis of phosphatidate
      to yield sn-1,2-diacylglycerol and inorganic phosphate. In mammalian systems,
      forms of phosphatidate phosphatase involved in glycerolipid synthesis and signal
      transduction have been identified. Forms of the enzyme involved in signal
      transduction have been purified and partially characterized. In yeast,
      phosphatidate phosphatases associated with the endoplasmic reticulum and
      mitochondria have also been purified and partially characterized. Information on
      phosphatidate phosphatases from mammals and yeast is useful in characterizing the
      enzyme from plant systems. This review examines progress on the characterization
      of phosphatidate phosphatases from mammals, yeast, and higher plants. The
      purification and characterization of the phosphatidate phosphatase involved in
      glycerolipid synthesis in developing oilseeds may lead to the identification of
      the encoding gene. Increasing our understanding of the enzymes of lipid synthesis
      in developing seeds will aid in the development of biotechnological strategies
      for seed oil modification.

PMID- 8869883
TI  - cis/trans isomerization of unsaturated fatty acids as possible control mechanism
      of membrane fluidity in Pseudomonas putida P8.
AB  - Exponentially growing cells of Pseudomonas putida had an increased ratio of
      saturated to unsaturated fatty acids in response to increased growth
      temperatures. Resting cells in which fatty acid biosynthesis was stopped reacted
      to a thermal increase by converting cis-monounsaturated fatty acids to trans
      isomers. cis/trans Isomerization of up to 60% of the unsaturated fatty acids was
      also activated by alcohols of different chain length. Their effective
      concentrations apparently depended on the lipophilic character of the alcohols.
      Also, a salt shock caused by the addition of NaCl resulted in the production of
      trans fatty acids. However, cells that were adapted to growth media of high
      osmolarity synthesized cyclopropane fatty acids instead of trans fatty acids.
      Activity of cis/trans-isomerase was dependent on the growth phase and was
      significantly higher during logarithmic growth than during the stationary phase.
      The results of this study agree with the hypothesis that the isomerization of cis
      into trans unsaturated fatty acids is an emergency action of cells of P. putida
      to adapt membrane fluidity to drastic changes of environmental conditions.

PMID- 8869884
TI  - Alterations in cell cholesterol content modulate Ca(2+)-induced tight junction
      assembly by MDCK cells.
AB  - Transepithelial electrical resistance (TER), a measure of tight junction (TJ)
      barrier function, develops more rapidly and reaches higher values after
      preincubation of MDCK cells for 24 h with 2 microM Lovastatin (lova), an
      inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase. While this effect was
      attributed to a 30% fall in cholesterol (CH), possible effects of lova on the
      supply of prenyl group precursors could not be excluded. In the current study,
      strategies were devised to examine effects on TER of agents that simultaneously
      lower CH and increase the flux of intermediates through the CH biosynthetic
      pathway. Zaragozic acid, 20 microM, an inhibitor of squalene synthase known to
      increase the synthesis of isoprenoids and levels of prenylated proteins, lowered
      cell CH by 30% after 24 h, while accelerating development of TER in the same
      manner as lova. TER was also enhanced, despite a 23% increase in the rate of
      [3H]acetate incorporation into CH, when total CH was reduced by 45% during a 2-h
      incubation with 2 mM methyl beta-cyclodextrin (MBCD), an agent that stimulates CH
      efflux from cells. The fact that the rate of TER development was diminished when
      cell CH content was elevated by incubation with a complex of CH and MBCD is
      further evidence that this sterol modulates development of the epithelial
      barrier. Cell associated CH derived from the complex was similar to endogenous CH
      with respect to its accessibility to cholesterol oxidase. Lova's effect on TER
      was diminished when 5 micrograms/mL of CH was added to the medium during the last
      11 h of incubation with lova.

PMID- 8869885
TI  - Effect of dietary n-9 eicosatrienoic acid on the fatty acid composition of plasma
      lipid fractions and tissue phospholipids.
AB  - n-9 Eicosatrienoic acid (ETrA), also known as Mead acid, is a minor fatty acid in
      essential fatty acid (EFA)-sufficient healthy subjects but is found at increased
      levels in EFA deficiency. This study examined the influence of dietary ETrA from
      a biological source on plasma and tissue ETrA. A synthetic fat-free diet was
      prepared to which was added Mut 48 oil which contains 19% ETrA (wt%) as well as
      other n-9 fatty acids. Blends of vegetable oils were used to achieve overall
      diets with 5% fat (wt%) and varying amounts of ETrA at two different dietary
      levels of linoleic acid (LA), approximately 4.4 and 19% of total fatty acids.
      These diets were fed to 5-week-old Dark Agouti rats for four weeks. Plasma lipid
      fractions and liver, spleen, and peritoneal exudate (PE) cells were analyzed for
      fatty acid composition. ETrA was present at up to 20% total fatty acids in plasma
      triglyceride, cholesterol ester, and phospholipid fractions. ETrA also
      accumulated to substantial levels in phospholipids of liver and spleen (up to 15%
      of total fatty acids) and PE cells (up to 11%). ETrA was found in plasma and
      tissue phospholipids in proportion to the amount of ETrA present in the diet. The
      incorporation was reduced in diets with higher LA content compared to diets
      containing similar amounts of ETrA but lower LA. All rats remained apparently
      healthy, and histological survey of major organs revealed no abnormality. While
      the long-term implications for health of ingestion of diets rich in ETrA remain
      to be established, rats appear to tolerate high levels of dietary ETrA without
      adverse effects. Dietary enrichment with ETrA warrants further investigation for
      possible beneficial effects in models of inflammation and autoimmunity, as well
      as in other conditions in which mediators derived from n-6 fatty acids can affect
      homeostasis adversely.

PMID- 8869886
TI  - Vitamin E inhibits fish oil-induced hyperlipidemia and tissue lipid peroxidation
      in hamsters.
AB  - Previous research has linked hyperlipidemia with increased serum concentrations
      of lipid peroxidation products; however, a specific association between diet
      induced oxidative stress and hyperlipidemia has not been studied. In the present
      study, the relationship between tissue lipid peroxidation and hyperlipidemia
      induced by ingestion of fish oil was examined. In Experiment 1, male Golden
      Syrian hamsters were fed semipurified diets composed of 1.6 wt% safflower oil
      plus 15.0 wt% of either butterfat (BF), safflower oil (SAFF), or high-cholesterol
      menhaden oil [MHO(H-CHOL)] semipurified diets for 27 d. The cholesterol contents
      of the diets were adjusted to 0.088%. The MHO(H-CHOL)-fed hamsters exhibited
      higher serum concentrations of total cholesterol, triglycerides, apolipoprotein
      B, and lipid peroxides when compared to the BF and SAFF diet groups. In a further
      study (Experiment 2), hamsters were fed for 27 d three dietary treatments: (i)
      MHO(H-CHOL) with no vitamin E content; (ii) a low-cholesterol menhaden oil
      containing high concentrations of vitamin E (2.5 mg tocopherol/g oil or dietary
      concentrations of 375 mg/kg) [MHO(L-CHOL) + E]; and (iii) the MHO(L-CHOL + E)
      with added cholesterol (595 mg/kg) [MHO(L-CHOL) + CHOL + E] to match the
      cholesterol content of the MHO(H-CHOL). The MHO(L-CHOL) + E and MHO(L-CHOL) +
      CHOL + E diet groups showed lower concentrations of serum cholesterol,
      triglycerides, and hepatic lipid peroxides than the MHO(H-CHOL)-treated group.
      Moreover, in contrast to the hypercholesterolemia caused by the MHO(H-CHOL)
      feeding, the MHO(L-CHOL)+ E and MHO(L-CHOL) + CHOL + E diets did not show a serum
      cholesterol-elevating action. This study supports the hypothesis that oxidative
      stress in the Syrian hamster could play a causal role in dietary-induced
      hyperlipidemia which can be inhibited by high vitamin E intake.

PMID- 8869887
TI  - A diet containing myristoleic plus palmitoleic acids elevates plasma cholesterol
      in young growing swine.
AB  - The objective of this study was to test the effect of a novel fatty acid mixture,
      enriched with myristoleic and palmitoleic acids, on plasma lipoprotein
      cholesterol concentrations. Weanling pigs were assigned to one of six groups and
      each group received a diet differing in fatty acid composition. Diets were fed
      for 35 days and contained 10 g added cornstarch/100 g (to provide baseline data)
      or 10 g added fatty acids/100 g. For those diets containing added fatty acids,
      extracted lipids contained 36% myristoleic plus palmitoleic acid combined
      (14:1/16:1 diet), 52% palmitic acid (16:0 diet), 51% stearic acid (18:0 diet),
      47% oleic acid (18:1 diet), or 38% linoleic acid (18:2 diet). With the exception
      of the cornstarch diet, all diets contained approximately 30% myristic acid.
      There were no significant differences in weight gain across treatment groups (P =
      0.22). All diets caused a significant increase in triglycerides and in total, low
      density lipoprotein, high density lipoprotein, and very low density lipoprotein
      cholesterol. The increase in total plasma cholesterol from pretreatment values
      was greatest in pigs fed the 14:1/16:1 and 18:1 diets. However, the increase in
      low density lipoprotein cholesterol from the pretreatment concentration was
      greatest in the 14:1/16:1-fed pigs. Increases in very low density lipoprotein
      cholesterol above pretreatment concentrations were lowest in 16:0-fed pigs and
      greatest in 18:1-fed pigs. Dietary fatty acids elicited changes in plasma fatty
      acids which generally were reflective of the diets, although the 18:0 diet did
      not alter plasma fatty acid concentrations and the 16:0 diet increased plasma
      16:0 only at the end of the study. These results demonstrated that the
      combination of myristoleic plus palmitoleic acids increased plasma cholesterol in
      young pigs, suggesting that fatty acid chain length, rather than degree of
      unsaturation, is primarily responsible for the effects of fatty acids on
      circulating lipoprotein cholesterol concentrations.

PMID- 8869888
TI  - Fatty acid composition of late embryonic and early postnatal rat brain.
AB  - The fatty acid (FA) composition and distribution in a variety of phospholipids
      (PL) and neutral lipids (NL) at two discrete stages during the embryonic rat
      brain development were investigated. Over 96% of the FA were acylated into fetal
      brain PL at embryonic day 17 after the peak of neuronal proliferation and at
      embryonic day 20, one day prior to delivery. Phosphatidylcholine constituted
      approximately 60% of the total PL pool, phosphatidylethanolamine (PE) 30%,
      phosphatidylserine (PS) 6%, and phosphatidylinositol (PI) 4%. The diacylglycerols
      and triacylglycerols constituted 1-2% of the fetal brain lipids. alpha-Linolenic
      acid (18:3n-3) and linoleic acid (18:2n-6) were found in very low amounts in all
      fetal brain PL and NL. The percentage of the n-6 polyunsaturated FA, consisting
      of arachidonic acid (AA), 22:4n-6 and 22:5n-6, remained unchanged in all the
      fractions, except in PI, in which the proportion of AA increased. The
      concentration of docosahexaenoic acid (DHA) increased with age in all the
      fractions, with the bulk of accumulation accounted for by its increase in PE and,
      to a lesser extent, in PS. This finding suggests a "DHA accretion spurt" during
      the last three days of pregnancy.

PMID- 8869889
TI  - The effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition on tissue
      levels of carnitine and carnitine acyltransferase activity in the rabbit.
AB  - Recently, a new class of lipid lowering agents [3-hydroxy-3-methylglutaryl (HMG)
      CoA reductase inhibitors] was introduced into clinical practice. The use of these
      agents could lead to a secondary deficiency in carnitine, which may manifest
      clinically as a myalgia/myositis-a side effect that is occasionally seen with
      this class of drugs. In the present study, we examined the effect of an HMG-CoA
      reductase inhibitor (lovastatin) on serum and tissue levels of carnitine and
      carnitine acyltransferase activities in the rabbit. Rabbits (n = 6) were fed chow
      containing lovastatin (30 mg/d) for 16 wk. Blood was collected and tissues
      (liver, heart, and skeletal muscle) harvested at sacrifice. Free and total
      carnitine were measured in serum and tissues by a radioenzymatic method.
      Carnitine acetyltransferase and carnitine palmitoyltransferase (CPT) activities
      were determined and expressed relative to DNA. Serum free (24.0 +/- 2.6 vs. 29.4
      +/- 3.1 microM) and total (35.1 +/- 4.7 vs. 52.8 +/- 8.8 microM) carnitine levels
      increased significantly with 16 wk of treatment. This increase in total carnitine
      was mainly due to an increase in the levels of serum acylcarnitine (12.7 +/- 3.1
      vs 26.5 +/- 5.7 microM). Tissue levels of total carnitine were significantly
      decreased by the treatment. Carnitine acetyltransferase was unaffected by the
      treatment, whereas there was a significant increase in the activity of CPT in the
      liver and heart.

PMID- 8869890
TI  - Dietary sunflower oil reduces plasma and liver triacylglycerols in fasting rats
      and is associated with decreased liver microsomal phosphatidate phosphohydrolase
      activity.
AB  - Plasma and liver lipids were studied in male weanling rats fed diets containing
      moderate levels of fat (6% by weight) as sunflower oil (SF diet, rich in linoleic
      acid), salmon oil (SM diet, rich in long-chain n-3 fatty acids), or a blend of
      peanut and rapeseed oil (PR diet, rich in oleic acid). After nine weeks of
      feeding, the fasting plasma cholesterol concentrations were 49 and 24% lower in
      groups SM and SF, respectively, as compared to group PR. Both dietary salmon oil
      and sunflower oil lowered the triacylglycerol concentration of plasma and liver
      but, unexpectedly, the response was higher with sunflower oil. Indeed, in group
      SM the values were 15 and 30% lower in plasma and liver, whereas in group SF,
      they were 24 and 53% lower, respectively. As compared to group PR, liver
      triacylglycerols and microsomes contained 2.5- and 2.3-fold less oleic acid,
      respectively, in group SF, and they were 9.2- and 3.2-fold enriched in n-3 fatty
      acids, respectively, in group SM. The liver triacylglycerol concentrations were
      correlated with changes in the microsomal Mg(2+)-dependent phosphatidate
      phosphohydrolase activity (r = 0.47, P < 0.01). As oleic acid, unlike long-chain
      n-3 fatty acids, is considered to promote the triacylglycerol synthesis and
      secretion, our findings suggest that changes in the membrane fatty acid
      composition could affect the triacylglycerol content of liver and plasma.
      Moreover, the availability within the liver, of oleic acid, predominantly
      incorporated into triacylglycerols, might limit the triacylglycerol production in
      SF-fed rats.

PMID- 8869891
TI  - Effect of a synthetic androgen on biliary lipid secretion in the female hamster.
AB  - This study was designed to elucidate the effect of the synthetic androgen,
      methyltestosterone, on bile flow and biliary lipid secretion in female hamsters.
      Animals were divided into four groups and fed the following diets: group 1,
      lithogenic diet for three weeks; group 2, lithogenic diet + 0.05%
      methyltestosterone for three weeks; group 3, lithogenic diet for six weeks; group
      4, lithogenic diet + 0.05% methyltestosterone for six weeks. At the end of each
      experimental period, the hamsters were operated on to establish external biliary
      fistulas. During the depletion of the endogenous bile acid pool (for two hours),
      the basal bile flow of group 4 was significantly smaller than that of group 3.
      Basal bile acid output was significantly lower in the methyltestosterone-fed
      groups 2 and 4 than in control groups 1 and 3. In contrast, groups 2 and 4
      secreted more cholesterol than groups 1 and 3. Group 4 had a higher ratio of
      cholesterol output to phospholipid output than group 3. Increasing doses of
      taurocholate were infused after the bile acid depletion period, and it was found
      that methyltestosterone did not change the bile acid independent bile flow. The
      increments in cholesterol or phospholipid output induced per increment of bile
      acid output (linkage coefficients) were analyzed by linear regression. The
      methyltestosterone-fed groups (groups 2 and 4) had a higher linkage coefficient
      of cholesterol output to bile acid output than the control groups (groups 1 and
      3). The linkage coefficients of phospholipid output to bile acid output of groups
      2 and 4 were also higher compared to groups 1 and 3. The linkage coefficient of
      cholesterol output to phospholipid output of group 2 was higher than that of
      group 1. These results suggest that methyltestosterone stimulated the cosecretion
      mechanism of cholesterol and phospholipid in bile associated with an increasing
      ratio of cholesterol to phospholipid. In conclusion, the synthetic androgen,
      methyltestosterone, caused a decrease in basal bile flow and bile acid secretion,
      and an increase in basal cholesterol secretion and the biliary cholesterol-to
      phospholipid ratio. These findings explain, in part, how methyltestosterone
      intensifies the formation of cholesterol gallstones in female hamsters.

PMID- 8869892
TI  - Salivary lipid profiles of the leech (Hirudo medicinalis).
AB  - Saliva was collected from sixteen leeches (Hirudo medicinalis). The saliva was
      analyzed for its total lipid content (3.26 +/- 0.31 mg of total lipids per 100 mL
      saliva). The lipids were separated into polar and nonpolar by chromatographic
      techniques. The neutral fraction was approximately 2/3 of the total, and the
      polar fraction was approximately 1/3 of the total lipids. Thin-layer
      chromatography was used to obtain the individual profiles of the polar and
      nonpolar lipids. Of the identified lipids, phosphatidic acids and free fatty
      acids represented the largest percentage. These results suggest that the leech
      contains a unique lipid distribution, and that some of these components may be
      potent phospholipases and lipases that probably are present in its saliva for the
      purpose of preventing plugging or healing of the wound in the attacked organism.

PMID- 8869893
TI  - Postchemotherapy connective tissue diseases--more than just rheumatism?

PMID- 8869894
TI  - The place of thalidomide in the treatment of inflammatory disease.

PMID- 8869895
TI  - Histocompatibility genes in antiphospholipid antibody syndrome.
AB  - The class II and especially the DQB1 locus of MHC genes, as well as C4 deficiency
      alleles appear to be associated with genetic risk for developing aPL. The
      extensive linkage disequilibrium among some of these risk factors makes it
      difficult to assign a causal role for any of these alleles by means of previous
      population studies of patients with APS; studies a patients with primary APS, in
      particular, have involved relatively few patients. Although there appear to be
      some overall similarities between the known MHC associations of primary APS and
      those of secondary APS, only a modest relative risk of APS is associated with MHC
      alleles, as discussed above, and other unknown risk factors must also be
      important. Whether these unknown risk factors for primary APS are different from
      those in secondary APS is an area for further investigation. In addition, new
      genes continue to be identified in the MHC class II and III regions that appear
      to have important roles in antigen processing and recognition. Interethnic
      studies of these and other alleles in large cohorts would be informative since
      ethnic groups of African, Japanese or Caucasian backgrounds often exhibit
      differing allelic linkage disequilibria within the MHC. Studies of linkage
      relationships in various MHC haplotypes have, for example, helped to clarify the
      role of MHC class II oligo alleles in rheumatoid arthritis. Further clarification
      of the roles of these MHC alleles will also depend on functional studies in
      experimental models and in vitro, to assess the roles of these risk factors in
      aPL production. The roles of non-MHC risk factors and of environmental agents
      that are operative within families also warrant further studies.

PMID- 8869896
TI  - Photosensitivity in systemic lupus erythematosus: laboratory testing of ARA/ACR
      definition.
AB  - OBJECTIVE: The aim of our study was to evaluate the prevalence of
      photosensitivity in SLE as defined by either clinical or laboratory assessment,
      the concordance of findings obtained by two methods, and the relationship between
      photosensitivity and clinical and immunological parameters. METHODS: Forty-four
      SLE patients and 31 healthy subjects were included. Patients and controls
      underwent a standard questionnaire testing and the minimal erythemal dose (MED)
      measurement performed by Dermalight-Blue Point. The standard questionnaire was
      designed in order to meet, as near as possible, the definition of
      photosensitivity included in the ARA/ACR criteria for classification of SLE.
      RESULTS: The prevalence of photosensitivity was (patients vs controls): 57% vs
      45% according to questionnaire; 79.5% vs 51.6% (P = 0.02) according to MED. The
      agreement between questionnaire and phototest was absent in SLE (kappa 0.01) and
      poor in controls (kappa 0.36). Discoid rash was significantly associated with
      questionnaire positive (P = 0.01) and renal involvement with questionnaire
      negative results (P = 0.02), serositis with MED abnormality (P = 0.03), malar
      rash and anti-Sm antibody with MED normal values (P = 0.03 and P = 0.01),
      respectively). Moreover, by multivariate analysis, malar rash and anti-Sm
      antibody significantly predicted MED-defined photosensitivity, with probability
      ranging from 42% (presence of both) to 92% (lack of both). CONCLUSIONS:
      Photosensitivity is frequently observed in SLE patients as well as in healthy
      subjects. Its prevalence is significantly higher in SLE than in controls only
      when it is detected using the laboratory method. However, due to the difficulty
      in objectively defining such manifestation, the disagreement between
      questionnaire and MED results was high and its clinical meaning appears
      ambiguous. Thus, the use of photosensitivity as a classification criterion for
      SLE remains questionable, at least when it is assessed according to the ARA/ACR
      definition.

PMID- 8869897
TI  - Ultraviolet-A1 (340-400 nm) irradiation therapy in systemic lupus erythematosus.
AB  - Ultraviolet-A1 (UV-A1) wavelengths have been found effective in mitigating signs
      and symptoms of disease activity in systemic lupus erythematosus (SLE) but
      studies have been uncontrolled. To rigorously assess the effectiveness and safety
      of daily low-dose UV-A1 irradiation as a therapeutic agent in this disorder we
      enrolled 26 women with SLE in an 18-week two-phase study. During the initial six
      week prospective, double-blind, placebo-controlled phase, the patients were
      divided into two groups; Group A was exposed to 60kJ/m2 of UV-A1 (340-400 nm)
      irradiation within a sunbed five days a week for three weeks and Group B was
      exposed for an equal amount of time to visible light of greater than > 430 nm
      (placebo). Each group was then crossed over for exposure to the other source for
      three weeks. During the second phase-2 weeks-patients and physicians were
      unblinded and patients were irradiated with progressively decreasing levels of UV
      A1 only. Twenty-five patients completed the six-week placebo-controlled phase of
      the study and eighteen patients participated for the entire 18 weeks. In Group A
      the systemic lupus activity measure (SLAM) score improved significantly after
      three weeks of five-day-a-week UV-A1 irradiation (P < 0.05), regressing to
      baseline during the three weeks of placebo irradiation. Improvement recurred and
      progressed with six weeks of three-day-a-week UV-A1 irradiation (P < 0.05). Group
      B patients responded negligibly to the three weeks of visible light, more sharply
      to UV-A1, and as with Group A, maximally to the six weeks of three-day-a-week UV
      A1 (P < 0.01). With twice- and then once-weekly UV-A1 irradiation the SLAM scores
      worsened slightly. All patients decreased their drug use. Anti-double-stranded
      DNA antibodies (anti-dsDNA) decreased significantly (P < 0.05) and anti-nuclear
      antibodies non-significantly. Side effects were negligible. Visible light had no
      significant effect. In conclusion, low-dose UV-A1 irradiation effectively,
      comfortably, and without apparent toxicity diminished signs and symptoms of
      disease activity in SLE.

PMID- 8869898
TI  - Antibodies to fibrin-bound tissue-type plasminogen activator in systemic lupus
      erythematosus are associated with Raynaud's phenomenon and thrombosis.
AB  - Fibrinolysis triggered by t-PA bound to fibrin is one of the main antithrombotic
      mechanisms. Defects in the fibrinolytic system-decreased tissue-type plasminogen
      activator (t-PA) activity and elevated levels of plasminogen activator inhibitor
      (PAI-1), in patients with SLE have been associated with an increased tendency to
      thrombosis. In the present study, 43 patients with SLE fulfilling the ACR
      criteria for the disease, were studied for the presence of autoantibodies to
      fibrin-bound t-PA, i.e. the physiological active form of this plasminogen
      activator. A solution of 200 IU/ml of t-PA was incubated with solid-phase fibrin
      prepared as previously described (Anal Biochem 1986; 153; 201-210). Sera diluted
      1:50 were incubated with fibrin-bound t-PA, the plates were then washed, and
      bound immunoglobulins were detected using a polyvalent peroxidase-labeled goat
      anti-human Ig. Plates coated with fibrin alone were used as controls. Sera were
      considered positive when A490/630 obtained with normal human sera in two
      independent test was greater than the mean plus 2 SD. Eleven of 43 (26%) SLE sera
      demonstrated antibody reactivity against fibrin-bound t-PA. Within the anti-t-PA
      positive group there was a higher proportion of SLE patients with severe
      Raynaud's phenomenon and thrombotic events when compared to the anti-t-PA
      negative group: 36% vs 6% and 18% vs 6% respectively. These results suggest that
      autoantibodies to fibrin-bound t-PA could play a role in the pathogenesis of
      vascular disease in some SLE patients.

PMID- 8869899
TI  - Variable regions of two murine antibodies that bind the SLE associated 16/6
      idiotype.
AB  - Experimental systemic lupus erythematosus can be induced in naive mice of
      different strains using a human monoclonal antibody bearing the 16/6 idiotype and
      a murine anti-16/6 Id monoclonal antibody designated 1A3-2. Herein we report the
      isolation of a second anti-16/6 Id antibody, 3F7-8, from BALB/c mice afflicted
      with experimental SLE. In contrast to the previously reported (1A3-2) anti-16/6
      Id monoclonal antibody, mAb 3F7-8 does not induce experimental SLE upon
      immunization. The variable heavy and light chains of both antibodies were cloned
      and their sequences were determined. The VH of mAb 1A3-2 was found to express a
      germ line gene from the Q52 family, with a high homology to an anti-lysozyme
      antibody. The VH of monoclonal antibody 3F7-8 was found to express a 7183 germ
      line gene, showing over 95% homology with the VH of 12 anti-Sm antibodies
      isolated from MRL-lpr mice. Based on sequence homology to other known antibodies,
      we further demonstrated that monoclonal antibodies 1A3-2 and 3F7-8 bind lysozyme
      and the Sm ribonucleoproteins, respectively, in addition to their binding to the
      16/6 Id.

PMID- 8869900
TI  - A clinical and serological comparison of familial and non-familial systemic lupus
      erythematosus in Ireland.
AB  - Seventeen families, in which the diagnosis of SLE could be verified in two
      relatives, were included in the study. The diagnosis was made according to the
      revised 1982 ARA criteria. We compared the 34 cases of familial SLE in these 17
      families with 34 non-familial SLE controls matched for age, sex, ethnicity and
      duration of disease. Comparisons were made for the presence of 26 clinical and 11
      serological features. The frequency of clinical features was similar between the
      groups. The frequency of anti-Ro antibody was higher in the non-familial group
      (15 out of 34 compared to 6 out of 34, P = 0.036, McNemar's test), although this
      was not significant after application of Bonferoni's correction for the number of
      comparisons. No cases of familial IgA or familial complement deficiency were
      identified. It was noted that 10 of the 34 non-familial patients and only one of
      the familial patients had the combination of anti-Ro antibody and
      photosensitivity. The findings of this study support the hypothesis that familial
      SLE and non-familial SLE are the same clinical entity, although there are
      differences in the subtypes of disease.

PMID- 8869901
TI  - Transverse myelopathy in SLE: clinical features and functional outcomes.
AB  - The objective of the study was to examine the clinical features of lupus patients
      who present with transverse myelopathy (TM) and ascertain functional outcomes
      when treated early with high dose corticosteroids and/or cyclophosphamide. Case
      records of nine patients who developed a total of 14 episodes of TM were
      retrospectively studied. All the patients were female and their ages ranged from
      21 to 59 years. Nine episodes of paraparesis, three of tetraparesis, one of
      numbness and one of neurogenic bladder were reported early in the diagnosis of
      SLE (median of two years). Neurogenic bowel and bladder and presence of ANA and
      ds-DNA were invariable. Urodynamics assessment in six patients showed abnormal
      detrusor behavior in all. CT scans and myelograms were uninformative and CSF
      studies were normal. ESR and complement levels were insensitive as markers of
      disease activity. The treatment regimens included pulses of methylprednisolone
      and/or cyclophosphamide followed by prednisolone and high dose prednisolone from
      onset. The functional outcomes were uniformly good-with independent ambulation in
      all except three (who needed assistive devices) and improvement of motor scores.
      Acute hospital stays were short (range of three to 45 days) whilst only two were
      referred for inpatient rehabilitation. Bladder abnormalities persisted despite
      motor recovery and would require long-term review.

PMID- 8869902
TI  - Restriction fragment length polymorphisms of constant region genes of
      immunoglobulin lambda chains in Venezuelan patients with systemic lupus
      erythematosus.
AB  - Previous studies suggest a potential association between human immunoglobulin
      (Ig) genes and susceptibility to systemic lupus erythematosus (SLE). Ig allotypic
      determinants seem to confer an increased risk for the disease in various ethnic
      patient populations. In this study we have examined the pattern of restriction
      fragment length polymorphisms (RFLP) of constant region lambda (C lambda) light
      chain genes in a group of 78 Venezuelan patients with SLE and 70 healthy
      controls. The frequency of the 8-kb allele and the 8/8 genotype was significantly
      lower in normal Venezuelan controls as compared to healthy British Caucasians (P
      = 0.0002 and 0.0007 respectively). In turn, Venezuelan controls showed a higher
      frequency of the 18-kb allele and the 18/18 genotype (P = 0.0002 and 0.0052
      respectively). However, there were no statistically significant differences in
      either parameter between Venezuelan SLE patients and healthy controls. Our study
      argues against a role for lambda light chain constant region genes in
      predisposition to SLE.

PMID- 8869903
TI  - Factor V Arg506-->Gln mutation in patients with antiphospholipid antibodies.
AB  - Antiphospholipid antibodies (APA) have thought to be implicated in the
      pathogenesis of both arterial and venous thrombosis. Because of heterogeneity of
      APA, direct evidence of their involvement in a thrombotic event is not yet
      available. Development of thrombosis in the antiphospholipid antibody syndrome
      (APS) may occur because of the presence of additional risk factors. Here we have
      analysed 60 patients with APA for the presence of the Arg506-->Gln mutation in
      factor V. Among them 26 suffered from deep venous thrombosis, 13 from arterial
      thrombosis and 21 had no history of arterial or venous thrombosis. In the first
      group four patients were found to be heterozygous and one homozygous for the
      factor V Arg506-->Gln mutation. None of the patients with the factor V mutation
      was found in the second and third group. The incidence of factor V mutation was
      significantly elevated in the group of patients with venous thrombosis. These
      data suggest that in patients with antiphospholipid antibodies the factor V
      Arg506-->Gln mutation may play a major role in the occurrence of venous
      thrombosis.

PMID- 8869904
TI  - Elevated levels of anticardiolipin antibodies and epilepsy in lupus patients.
AB  - To examine the association between anticardiolipin (aCL) antibodies and epilepsy,
      we investigated the serum titers of aCL antibodies in a total 252 systemic lupus
      erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases
      with epilepsy which were not attributable to any causes other than SLE were
      identified after being followed-up for five years. The clinical manifestations
      were recorded and blood samples were tested for the presence of aCL antibodies
      (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2
      (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM
      and IgA aCL antibodies. There was a dose-response relationship between risk of
      seizure and the baseline serum level of aCL antibodies (P < 0.01). The odds ratio
      of developing seizure were 3.7 for those who had a high level of aCL antibodies
      compared with those without a detectable level of aCL antibodies as the referent.
      Our results indicate that epilepsy as a primary neuropsychiatric event among
      lupus patients is associated with a high titer of aCL antibodies.

PMID- 8869905
TI  - Antiphospholipid antibodies and retinal vascular disease.
AB  - BACKGROUND: Antiphospholipid antibody retinopathy is a rare and poorly defined
      clinical entity in which the proper diagnosis has important ocular and systemic
      implications. The clinical course of five patients with antiphospholipid antibody
      retinopathy is described and the role of such antibodies in idiopathic retinal
      venous occlusive disease is investigated. METHODS: Five case reports are
      presented highlighting the presentation, course, therapy, associations and
      outcomes of patients with antiphospholipid antibody retinopathy. In addition,
      twenty additional patients presenting with idiopathic retinal venous occlusive
      disease were tested for the presence of antiphospholipid antibodies. RESULTS: All
      five patients with antiphospholipid antibody retinopathy had diffuse retinal
      vascular occlusion. All five patients presented with associated rheumatologic
      disease, including three with lupus or lupus-like disease. Antibodies to
      antiphospholipid were not detected in any of the twenty patients with idiopathic
      retinal venous occlusive disease. Prompt panretinal photocoagulation together
      with varying regimens of corticosteroids, immunosuppressives, or warfarin was
      partially successful in stabilizing the ocular and systemic disease. CONCLUSION:
      The diagnosis of antiphospholipid antibody retinopathy should be suspected in
      patients with diffuse retinal vaso-occlusion, particularly when characterized by
      involvement of both arteries and veins, neovascularization at presentation, and
      symptoms of symptoms of systemic rheumatologic disease. Antiphospholipid
      antibodies do not appear to play an important role in idiopathic retinal vein
      occlusions.

PMID- 8869906
TI  - Osteonecrosis in systemic lupus erythematosus, steroid-induced or a lupus
      dependent manifestation?
AB  - Osteonecrosis (ON) is a well-known complication in patients with systemic lupus
      erythematosus (SLE) often associated with steroid therapy. In a cohort of 280 SLE
      patients followed over the last 10 years, seven patients developed symptomatic
      ON, one of them after septic arthritis of the hip. Two other patients developed
      ON several years after discontinuing steroids. One patient developed ON of both
      humeral and femoral heads within a few months after the diagnosis of SLE. When we
      compared the cumulative steroid doses taken by our patients with those described
      in other reports (43,700 mg and 45,300 mg, respectively), our patients received
      less steroids (38,834 mg). We found no increased frequency of Raynaud's
      phenomenon, leukopenia, anti-phospholipid antibodies, or a flare of SLE activity
      in our patients with ON, factors which have been reported to be associated with
      ON. Various pathogenic mechanisms, which could lead to ON in SLE patients are
      discussed.

PMID- 8869907
TI  - Modulation of experimental systemic lupus erythematosus with linomide.
AB  - OBJECTIVE: The objective of this study was to assess the beneficial effects of an
      early administration of low dose linomide, a new immunomodulator, in an animal
      model of experimental systemic lupus erythematosus (SLE). METHODS: Experimental
      SLE was induced in naive BALB/c mice, by immunization with anti-DNA mAb (MIV-7).
      Control Mice immunized with irrelevant human IgM served as controls. The
      immunized mice were treated with linomide (0.1 mg/ml in the drinking water), four
      weeks prior to the first immunization, at an early stage of the disease induction
      (one month after boost injection), or at a later stage (3 months following boost
      immunization). The treatment duration was 3 months in all schedules. The follow
      up studies continued for 8 weeks after discontinuation of the treatment. The
      presence in the serum of autoantibodies against ssDNA, dsDNA histones,
      phospholipids and an irrelevant autoantigen-pyruvate dehydrogenase, was
      determined by enzyme-linked immunosorbent assay (ELISA). The clinical parameters
      assessed included erythrocyte sedimentation rate, peripheral blood cell counts
      and proteinuria. RESULTS: There was a 50-64% decrease in autoantibody levels in
      the sera of mice immunized with anti-DNA (MIV-7) mAb at the early stage of
      experimental SLE in mice which received linomide for a period of 3 months. No
      effect of linomide was noted in mice which received the drug during the later
      stages of experimental SLE when the disease was fully developed. Linomide had a
      preventive effect on the induction of experimental SLE in naive mice, when the
      treatment was initiated before the induction of the disease. This effect was
      abolished following cessation of the treatment. CONCLUSIONS: Linomide proved to
      be effective at the early stages of induction of the experimental SLE. However,
      the autoantibody levels rose following discontinuation of the therapy.

PMID- 8869908
TI  - Superior sagittal sinus thrombosis in a patient with systemic lupus
      erythematosus.
AB  - Cerebral venous thrombosis is a rare cause of focal neurological damage in
      patients with SLE. We describe a patient with SLE who presented with a focal
      neurological deficit and subsequently developed increased intracranial pressure.
      A superior sagittal sinus thrombosis was diagnosed by MRI. The association
      between SLE and superior sagittal sinus thrombosis is discussed. Early diagnosis
      is essential because treatment leads to a positive clinical outcome.

PMID- 8869909
TI  - Late development of anti-La/SS-B antibodies in a patient with Sjogren's syndrome
      and high titer anti-Ro/SS-A antibodies.
AB  - The frequent coexistence of anti-Ro and anti-La autoantibodies is well described,
      however, there is little evidence of sequential development of these two
      autoantibodies. We report a case of typical Sjogren's syndrome with high titer
      anti-Ro antibodies, who subsequently developed anti-La antibodies later in the
      course. This case suggests that the anti-La antibodies may actually follow the
      anti-Ro antibodies in some cases as hypothesized in the concept of linked set of
      autoantibodies, analogous to development of anti-Sm in certain anti-nRNP antibody
      positive SLE patients and animal models.

PMID- 8869910
TI  - Humoral response in spontaneous and experimental autoimmunity to the ribosomal P
      proteins.

PMID- 8869911
TI  - Age-related responses of right ventricle in swim-trained rats: changes in lactate
      and pyruvate contents and lactate dehydrogenase activity.
AB  - Age related changes in carbohydrate substrates such as, glucose, glycogen,
      pyruvic acid and lactic acid and the activity of lactate dehydrogenase (LDH) and
      LDH isoenzyme profile were evaluated in the right ventricle (RV) of swim-trained
      rats of 6- (adult), 12- (middle-aged) and 18- (old) months-of-age. Moderate
      hypertrophy was seen in the heart and RV in response to training in all age
      groups with the 12 months exhibiting a significant increase. While resting levels
      of pyruvate and glucose in the RV showed small elevations in adult and middle
      aged rats, lactic acid showed reductions in all ages. Glycogen supercompensation
      was seen in the RV of trained animals. These age-related alterations in RV were
      associated with decreases in blood lactic acid and glucose in the trained rats
      belonging to all ages. Total protein of the RV decreased with age and exercise
      increased the content. Total LDH and M4-LDH activities decreased with age.
      However, training increased their activities in all ages. These changes in the RV
      suggests that swimming activity produces adaptations (e.g. increased LDH and M4)
      in all age groups. Considering the degree of adaptations, it can be suggested
      that adult and middle-aged are suitable for initiating swim-training programs,
      but not in old age.

PMID- 8869912
TI  - Age- and training-related events in active T subpopulation. Changes in
      polyphosphoinositide metabolism during mitogenic stimulation.
AB  - To examine the effects of age and training on the active T subpopulation we
      considered elderly amateur cyclists over 65 in comparison with young amateur
      cyclists and young and aged sedentary healthy controls. Significant differences
      were observed between trained and sedentary elderly subjects consisting of an
      increase in the percentage of active E rosettes after 4 and 24 h of in vitro PHA
      stimulation, and of a decrease in the in vitro phosphorylation of
      phosphatydylinositol 4,5-bisphosphate (PtdInsP2) and a corresponding increase in
      phosphatydylinositol 4-phosphate (PtdInsP) in the early steps of the mitotic
      response. Our findings support the hypothesis of the involvement of inositol
      lipids in controlling the expression of lymphocyte surface receptors.

PMID- 8869913
TI  - Changes in NADPH-diaphorase neurons of the rat laterodorsal and pedunculopontine
      tegmental nuclei in aging.
AB  - The aim of the present study was to compare the morphological pattern and the
      quantitative parameters of nitric oxide (NO)-containing neurons in the
      laterodorsal (LTD) and pedunculopontine (PPN) tegmental nuclei of 3-, 12- and 26
      month-old rats. NADPH-diaphorase (NADPH-d) histochemical reaction, as a marker of
      the cholinergic neurons in the two mesopontine nuclei, and computer-assisted
      image analysis were used. The relationships between the neurons stained for NADPH
      d and choline acetyltransferase (ChAT) were examined using a double-labelling
      procedure. The results demonstrated only occasional ChAT positive somata that did
      not exhibit NADPH-d staining. The volume of the LTD and PPN and the number of
      NADPH-d neurons remained unaltered with advancing age. However, ANOVA
      demonstrated a significant effect of age and level on the cross-sectional areas,
      maximum diameters and staining intensity of NADPH-d somata in the LTD and PPN.
      The three parameters were reduced in 26-month-old rats compared to 3-month-old
      rats. The changes in the morphological appearance of NADPH-d somata and processes
      as well as the quantitative analysis pointed to age-related neuronal atrophy. It
      was accompanied by hypertrophy of some neighbouring neurons, suggesting a
      compensatory mechanism which would counteract the degenerative changes. The age
      dependent alterations in the LTD and PPN were rather similar.

PMID- 8869914
TI  - Age- and strain-related changes in tissue transglutaminase activity in murine
      macrophages: the effects of inflammation and induction by retinol.
AB  - We describe differences in the activity of tissue transglutaminase (TGase)
      between resident and inflammatory mouse peritoneal macrophages as a function of
      age. Our results established the following observations: (a) resident macrophages
      from senescent mice expressed higher basal TGase activity than those from young
      mice; (b) Maximal TGase activity on day 3 of thioglycollate injection was lower
      by 24% in inflammatory macrophages from senescent as compared to young animals;
      (c) in contrast, as the inflammatory response abated (days 4-6), the incremental
      decrease in TGase activity in old was lower than in young animals; (d) in vitro
      activation of resident macrophages by retinol and mouse serum was more effective
      in inducing TGase activity from outbred CD-1 young mice than from inbred C57BL/6J
      young mice (age differences were also more prominent in the CD-1 mouse strain);
      and (e) Retinol and mouse serum effectively inhibited the production of
      superoxide in young mice, thereby demonstrating an inverse correlation between
      TGase activity and superoxide production. In old animals, however, the production
      of superoxide was not decreased, nor was TGase increased. Although,
      paradoxically, resident macrophages from senescent mice were a priori more
      activated than those from young ones, it is concluded that macrophages from young
      mice respond better than those from old ones to stimuli they encounter, either
      during inflammation or under physiological stimulation.

PMID- 8869915
TI  - Age-related aneuploidy analysis of human blood cells in vivo by fluorescence in
      situ hybridization (FISH).
AB  - All prior studies on human age-related chromosomal analysis were done using only
      metaphase figures derived from lymphocyte cultures in vitro. However, we believe
      that this procedure may provide only partial information, since the chromosomal
      abnormalities probably hidden in non-dividing and/or terminally differentiated
      leukocytes will not be detected by this method. We, therefore, have attempted to
      analyze the nature and extent of chromosome-specific aneuploidy at interphase by
      fluorescence in situ hybridization (FISH) in differentiated myeloid cells in vivo
      derived from various age-group people. Our data from an analysis of 30,032 cells
      derived from 12 healthy donors indicate that there is an increase in the mean
      percentages of myeloid cells with chromosome-specific aneuploidy in the older
      groups as opposed to that of the younger groups. This increase is applicable to
      all the three cell types examined (promyelocytes, metamyelocytes and polymorphs).
      In both the younger and older females, the relatively higher mean frequencies of
      cells with aneuploidy were noted for chromosome nos. 4, 6 and the X, whereas the
      lowest mean frequencies of cells with aneuploidy were consistently observed for
      chromosome no. 3. In the younger and older male donors, similar to the female
      donors except the X chromosome the higher percentages of aneuploid cells were
      observed for chromosome nos. 4 and 6 whereas the lowest mean frequencies of
      aneuploid cells were noted for chromosome no. 3. Among the five autosomes
      studied, chromosome no. 3 consistently yielded the lowest frequency of aneuploidy
      in all the three cell types derived from both the younger and older groups of
      males and females. This could presumably mean that the maintenance of a very high
      frequency of cells with disomy for chromosome no. 3 might be more beneficial for
      the process of survival and/or differentiation of myeloid cells as compared to
      that of other autosomes such as chromosome nos. 4 and 6. Among the five autosomes
      studied, chromosome no. I exhibited the highest rate of increment in the
      aneuploidy values of both males and females with advancing age.

PMID- 8869916
TI  - Human chorionic gonadotropin hormone is antiviral.
AB  - Although it is well known that human chorionic gonadotropin maintains the corpus
      luteum's ability to secrete estrogen and progesterone, I believe that it serves
      yet another important function. Early evidence suggests that human chorionic
      gonadotropin is a broad-spectrum antiviral/immune potentiator.

PMID- 8869917
TI  - Alzheimer's disease, Kuf's disease, tellurium and selenium.
AB  - The possible role of the abnormal trace element tellurium in the pathogenesis of
      Alzheimer's disease is examined. Tellurium has been reported to produce cognitive
      impairment and cerebral lipofuscinosis in rats-changes akin to those seen in
      Kuf's disease, a condition which shares certain clinical and neuropathological
      features with Alzheimer's disease. Tellurium can damage mitochondria; defects in
      mitochondrial energy metabolism may be relevant to the pathogenesis of
      neurodegenerative disease. The deficiency of selenium, which may act
      physiologically as an antagonist of tellurium, in the Alzheimer's disease brain
      would also be in keeping with the hypothesis of tellurium toxicity as a factor in
      the pathogenesis of Alzheimer's disease.

PMID- 8869918
TI  - What good is it to get old?
AB  - The physiologic basis for aging is still incompletely understood, and most
      investigators have looked at aging as a process of decay without any clear
      adaptive advantage to the species. It is proposed that aging has potential
      evolutionary advantages, and that the aging process may have been the subject of
      positive selection.

PMID- 8869919
TI  - The third heart sound is the result of a shock wave caused by the ventricular
      inflow velocity exceeding the wave velocity.
AB  - The genesis of the third heart sound (S3) has been debated for over a century. An
      hypothesis is presented which proposes that S3 is the result of a shock wave
      which is generated when the ventricular inflow velocity exceeds the local wave
      velocity. Echocardiographic data that support the hypothesis are presented from
      patients with and without an S3.

PMID- 8869920
TI  - Herpetic viruses and spontaneous recovery in melanoma.
AB  - The malignant melanoma may display extremely variable forms of development, from
      clinical forms with a lethal course to the unforeseeable situations of
      spontaneous cures. The basic immunotherapeutic procedures, as well as hypotheses
      regarding the mechanisms involved in courses towards spontaneous regressions, are
      presented. Since viruses of the herpes genus are involved in the mechanisms
      assumed to be at the basis of spontaneous regressions, it is suggested that these
      viruses (selected strains) be used in the clinic, in order to check the advanced
      hypothesis, an opportunity which could permit to study also the very probable
      therapeutic alternative offered by this virus, namely the association of the well
      known immunotherapeutic methods.

PMID- 8869921
TI  - The possible role of prolactin in the immunopathogenesis of multiple sclerosis.
AB  - Multiple sclerosis is a disease of the central nervous system characterized by
      multiple areas of inflammation and demyelination in the white matter of brain and
      spinal cord. A complex mechanism of the immunopathogenesis of the disease
      involves mononuclear cells infiltrating multiple sclerosis plaques, as well
      numerous cell products, such as interleukins, interferons, certain growth
      factors, etc. Some recent studies have emphasized the immunoregulatory role of
      certain neuroendocrine peptides, including prolactin. Prolactin, a hypophyseal
      hormone which is also produced by activated immunocytes, has been considered in
      this work as a co-factor participating in the immunopathogenic mechanism of
      multiple sclerosis.

PMID- 8869922
TI  - Electrostatic attraction: the driving force for the presynaptic vesicle-cell
      membrane fusion.
AB  - In this theoretical conception, it is suggested that the driving force for
      presynaptic vesicle-cell membrane fusion during action potential that results
      with the neurotransmitter release is the electrostatic attraction of the
      differently charged outer lipid layer of the presynaptic vesicle membrane and the
      inner lipid layer of the cell membrane. All other previously described processes
      that take place during presynaptic vesicle-cell membrane fusion could serve to
      modulate the basic electrostatic process presented here.

PMID- 8869923
TI  - Malaria and macrophage function in Africans: a possible link with autoimmune
      disease?
AB  - Systemic lupus erythematosus and sarcoidosis, both diseases in which immune
      responses are aberrant, are not found in Africans in West Africa, but their
      prevalence in people of West African descent in the USA and UK is higher than
      that for white people. It is argued here that malaria both prevents these
      diseases in West Africa by its effects on macrophage function, and has also
      selected for a predisposition to them.

PMID- 8869924
TI  - Is spin lattice relaxation time independent of species?
AB  - It has been suggested that the spin lattice relaxation time is independent of
      species. It was further stated that, from a nuclear magnetic resonance
      standpoint, the human muscle is similar to rat muscle and to pig muscle, etc.
      However, it is observed that, in normal liver and kidney of human, rat, dog,
      rabbit and hamster, spin lattice relaxation time varies in different species as a
      function of percentage of body-weight of the organ. The result shows that spin
      lattice relaxation time is different in different species because of the organ
      weight which in turn dictates the metabolism in an individual species.

PMID- 8869926
TI  - A new cancer hypothesis.
AB  - Despite intensive efforts to cure breast cancer, treatment generally fails, as
      evidenced by the age-adjusted mortality rate for breast cancer. For 60 years,
      breast cancer mortality remained virtually constant. As treatment failed to
      improve the life prospect of the average patient, it is based on false premises,
      e.g. Halsted's hypothesis, according to which the tumor is the only threat to the
      patient. Yet there is more to cancer than just the tumor. Two hallmarks of
      cancer, cachexia, and paraneoplasia, are usually ignored, since it is assumed
      that they are caused by the tumor. But what if it is the other way round, and
      cancer is first of all a cachexia accompanied by a tumor? At least this could
      explain why, in most cancers, treatment fails. Cancer is a chronic systemic
      disease with local manifestations like arteriosclerosis, which is also systemic
      and manifested solely by its local manifestations, e.g. stroke and myocardial
      infarction. In the same way as treatment of an ailing heart does not cure the
      underlying arteriosclerosis, tumor removal does not cure cancer, as it is
      'metabolically' systemic. It is proposed here that carcinogens deplete a vital
      substance and induce a metabolic deficiency that ends in cachexia. In order to
      survive, the organism grows a protective organ-the tumor-that replenishes the
      missing substance. During the preclinical phase of cancer, deficiency is slight
      and compensated only by a minute tumor. With time, it gets worse and the tumor
      has to grow more and more in order to make up for the loss, causing pain and
      secondary damage to vital functions. The patient seeks help and the disease
      starts its clinical course. When deficiency worsens, the patient becomes
      cachectic and dies. Such a metabolic relationship exists in pernicious anemia,
      which illustrates how a tumor might be protective. Cancer is viewed here as
      pernicious cachexia induced by the loss of a vital metabolite and compensated by
      the tumor. Until the discovery of the missing substance, treatment ought to
      preserve the tumor and alleviate its secondary manifestations.

PMID- 8869925
TI  - Exploitation of hypoxia for radiation therapy: a lesson from phenothiazines.
AB  - In experimental radiation therapy of tumours, phenothiazines are known to
      sensitize hypoxic cancer cells while offering protection to the normal
      surrounding tissue. It is hypothesized that the differential radiosensitization
      of tumour cells and radioprotection of normal cells by phenothiazines is related
      to the presence of Fe2+ and Fe3+ ion concentration respectively. As a result of
      changed biochemical environment such as pH, hypoxia and accumulation of ferritin,
      the Fe2+ ion concentration in tumours, especially in the hypoxic cells, is
      expected to be higher (and to be further enhanced by irradiation) than in the
      well-oxygenated normal cells. In normal cells, iron would predominantly be in the
      Fe3+ form, which might increase the protective effect of phenothiazines. A many
      fold increase in radiation effect has been shown by us in vivo as well as in
      vitro systems in the combined presence of phenothiazines and Fe2+ ions. Our
      findings suggest that the hypoxic condition can be exploited for radiation
      therapy by employing suitable metal-based chemomodulation.

PMID- 8869927
TI  - Dental and research transmission of acquired immune deficiency syndrome? Or, is
      there any evidence that human immunodeficiency virus is sufficient to cause
      acquired immune deficiency syndrome?
AB  - An unpublished report of three laboratory workers exposed to concentrated human
      immunodeficiency virus cultures and one anomalous case of putative dental
      transmission to six patients represent the only evidence of acquired immune
      deficiency syndrome developing in the absence of immunologic cofactors such as
      exposure to sexually transmitted diseases, drugs, malnutrition, and alloantigens.
      A review of the Centers for Disease Control (USA) files shows that all six dental
      patients had identified risks for human immunodeficiency virus infection other
      than dental treatment, and evidence of cofactor exposures. Several demonstrated
      immunologic abnormalities prior to dental treatment. These data were ignored by
      the Centers for Disease Control. Furthermore, known rates of human
      immunodeficiency virus transmission by blood clotting factor use (1 infection per
      20 exposures) and percutaneous exposure (1 per 250) make the number of patients
      the dentist would have had to expose to get six infections unrealistic (circa 120
      1500). Thus, no clear-cut evidence exists for human immunodeficiency virus
      infection in the absence of predisposing immunologic cofactors.

PMID- 8869928
TI  - Further observations on the etiology of pre-eclampsia: mobilization of toxic
      cadmium-metallothionein into the serum during pregnancy.
AB  - Cadmium-metallothionein, mobilized from the liver, might be the toxic serum
      factor associated with pre-eclampsia. We base this on four documented concepts.
      First, during pregnancy, maternal physiology adjusts to assure the fetus of the
      proper amounts of nutrients necessary for growth. Our focus is on zinc and
      progesterone. Second, because zinc and cadmium are similar, they compete for
      binding sites. Our focus is on the storage protein metallothionein. Third, the
      manifestations of cadmium toxicity closely mimic the manifestations of toxemia
      (i.e. hypertension, proteinuria, edema). Our focus is on cadmium-induced
      endovasculitis. Fourth is the concept that metallothionein-bound cadmium can be
      mobilized from the liver into the serum during pregnancy as it follows the
      mobilization of metallothionein-bound zinc. Our focus is on the extreme toxicity
      of extracellular cadmium-metallothionein. We correlate these four concepts into a
      rational theory on the etiology of toxemia, and we suggest a method of proof.

PMID- 8869929
TI  - Differentiation arrest by autologously replicating DNA loops formed along
      differentiation pathway: an hypothesis of carcinogenesis.
AB  - The current hypothesis attempts to explain tumor development from the perspective
      of deoxyribonucleic acid structural changes rather than mutational alterations of
      single or multiple genes. The hypothesis postulates that stable deoxyribonucleic
      acid loops capable of autologous replication, translation and expression cause
      cell-differentiation arrest and contribute to the carcinogenesis and various
      abnormal biological behaviors of tumor. The formation of deoxyribonucleic acid
      loops at particular steps along the differentiation pathway determines tumor
      phenotype, grade and behavior. The outcome of deoxyribonucleic acid loop
      formation in a cell is highly affected by the differentiation signals imposed by
      the cell's differentiation microenvironment which is considered as a very
      important regulatory factor during tumor development in this hypothesis. The
      incompatibility of adhesion molecules between tumor cells and surrounding normal
      cells is proposed in this hypothesis as a major reason for separation of tumor
      cells from primary lesions and thus metastasis. This hypothesis also postulates
      that tumor invasion is caused by the expression of proteins related to the
      transient invasive phenotype of normal cells in physiologic process that is
      controlled by the genes within autologous deoxyribonucleic acid loops.

PMID- 8869930
TI  - Cardiomyopathies and oxidative stress.
AB  - Cardiomyopathies are the group of diseases affecting the cardiac muscle. Although
      they have never been related to oxidative stress diseases, an analysis of the
      causes of these pathologies reveals the presence of a pro-oxidative agent or that
      the intracardiocytic balance between oxidation and antioxidation has been broken.
      In support of this hypothesis, we analyse the pro-oxidative factors which co
      operate with other factors or by themselves to promote the development of this
      group of pathologies. We show also data demonstrating that the tissue and
      cellular damages are characteristic of an oxidative stress situation. Finally, we
      present evidence that in some cases of particular cardiomyopathies, the use of
      antioxidative strategies greatly improves the health of the patients. Therefore,
      we suggest that the use of antioxidants can be an alternative or complementary
      therapy in this group of diseases.

PMID- 8869931
TI  - Artificial liver support: the pipe dream of today should be the reality of the
      near future.
AB  - The title of this article is taken from an interesting Letter to the Editor
      entitled 'Artificial liver support-Pipe dream or reality' by Cattral and Levy of
      the Toronto Hospital, Canada, published in the New England Journal of Medicine
      1994, in which the authors persuasively propose possibilities of artificial liver
      support and suggest its advantages. We find that their suggestions agree with the
      core of our thoughts on this subject. The present article deals with the concept
      of implanting livers taken from humans, primates or non-primates (e.g. hog) into
      patients in parallel with their own metabolically fatigued or cirrhotic livers,
      with minimal surgical manipulation, as a prelude to total artificial liver
      support via a liver dialysis device. While the possibility exists that the host
      liver may recover function, a donor liver, whether implanted into the patient's
      abdomen or connected in vitro to the patient's circulatory system
      extracorporeally, may provide the host liver respite and a period for recovery
      and proliferation, if possible. Once recovery is under way, the donor liver may
      be removed and the patient will not experience the usual risks of rejection and
      the necessary side-effects of immunosuppression associated with conventional full
      hepatectomy and donor transplantation. The viability of a liver implantation
      model in rats is correlated in this article with hepatic acute phase response.

PMID- 8869932
TI  - Biogenesis of hepatic acute-phase response to trauma.
AB  - The bioorganic pathway(s) of hepatic acute-phase response in rat to single and
      compounded traumata triggered either by chemical or physical injury has been re
      evaluated for the purpose of advancing a better understanding of mechanisms of
      hepatic regeneration. These insights would be useful in cases of liver cirrhosis
      and end-stage liver diseases and may allow avenues of surgical management other
      than liver transplantation. Mechanisms of acute-phase response in rat to a single
      inflammatory stimulus, e.g. intoxication with phalloidin, alpha-amanitin,
      subcutaneous administration of carageenan, subcutaneous implantation of Yoshida
      sarcoma or i.p. administration of Zajdela ascites are discussed and compared with
      (a) acute-phase response to intoxication by various factors leading to the
      development of liver cirrhosis, and (b) acute-phase response of nascent
      hepatocytes where hepatic regenerative activities were induced by chemical
      intoxication or surgical partial hepatectomy. Interestingly, hepatic acute-phase
      response was not limited only to these injuries outlined above but also to
      psychological conditions.

PMID- 8869934
TI  - Acute leukaemia following renal transplantation.
AB  - Four renal transplant patients on immunosuppressive therapy who presented with
      acute myeloid leukaemia are described. In two cases, azathioprine may have played
      an important role as a cofactor in leukaemogenesis. In a third case, the
      alkylating agent cyclophosphamide may have contributed. All patients were treated
      for leukaemia with full doses of cytotoxic chemotherapy and, in each case, a
      functioning renal allograft was preserved throughout the treatment despite
      attenuation of immunosuppressive therapy. Three patients achieved complete
      remission. Of the three, one is surviving at 2 years and two expired during the
      pancytopenic phase of their treatment with no active leukaemia present, and with
      intact renal function. As increasing expertise in the field of organ
      transplantation allows patients to survive longer, such patients' exposure to
      immunosuppressive and potentially leukaemogenic drugs is prolonged. The risk of
      secondary neoplasia has been previously documented in this population. Two of the
      four cases reported here suffered from polycystic kidney disease as their
      underlying condition. While this report suggests that the leukaemias are related
      to renal transplantation, we cannot rule out an association with the underlying
      disease which led to the transplant. This report further suggests that the
      leukaemia that develops in such patients may respond to standard therapy, and
      that such treatment does not compromise the transplanted kidney.

PMID- 8869933
TI  - Idiotype-specific T cells in multiple myeloma: targets for an immunotherapeutic
      intervention?
AB  - In this paper, the results of some recent studies on idiotype-specific T cells in
      human multiple myeloma (MM) and monoclonal gammopathy of undetermined
      significance (MGUS) are discussed. By using different in vitro measurements such
      as 3H-thymidine incorporation and ELI-SPOT assay, idiotype-specific T cells have
      been demonstrated in most of MM and MGUS patients. Based on the cytokine
      secretion profiles, idiotype-specific T cells were found to comprise both Th1 and
      Th2 cells. A Th1 type immunity was found preferentially in indolent disease and a
      Th2-like response predominated in advanced MM, suggesting a specific T-cell
      regulation of the tumor B-cell clone. The mode of T-cell recognition of id
      determinants on M-components has been studied. We found that idiotype-specific T
      cells recognized processed id determinants presented by MHC class II (HLA-DR)
      molecules on APC. B cells were much more efficient APC than monocytes. With the
      aim to induce or to amplify an idiotype-specific T-cell response, we have
      immunized MM patients with the autologous M-component precipitated in aluminum.
      Three out of the five patients showed an induction of specific cellular and
      humoral immunity. Nevertheless, the role for such immunity in controlling the
      tumor clone remains to be established.

PMID- 8869935
TI  - Curable and non-curable malignancies: lessons from paediatric cancer.
AB  - The tremendous progress achieved in understanding the molecular basis of cancer,
      was unfortunately not followed by a mutual improvement in the morbidity and
      mortality of adult cancer. In contrast, the success rate achieved in paediatric
      oncology has increased significantly during the past 30 years, and more than two
      thirds of the children with cancer can now be cured. p53 has been shown to have a
      central role on apoptosis in various cells. As apoptosis is a final common
      pathway for much of our anti cancer therapy, resistance to apoptosis due to a
      normal activity of p53 is an important mechanism of tumor resistance and
      treatment failure. Contrary to the findings in most adult tumors, where about 50%
      of the tumors lack p53 activity, the rate of p53 mutations in childhood cancer is
      surprisingly low. This may be the key to the much better prognosis of children
      with cancer. In most adult tumors, multiple genetic events, between five and
      seven, are usually involved. The oncogenes involved in such tumors usually
      represent those located upstream of the nuclear transcription factors. In most
      paediatric tumors, in contrast, the initiating event is the activation of nuclear
      transcription factors secondary to chromosomal translocations. It can be
      speculated that multiple events activating various components of the signal
      transduction machinery are needed for tumorigenesis, and hence the evolution and
      progression of such tumors is slow. Moreover, if the malignant cell has to
      accumulate multiple mutations, the chances of crippling the apoptotic mechanism
      are higher. Genomic instability evidenced by microsatellite variation has been
      found in colon, pancreas, breast, liver and ovarian adult tumors, and not in
      paediatric tumors. As multiple somatic mutations are needed for the initiation
      and progression of the common adult malignancies, inherent genomic instability
      can dispose to accumulation of multiple mutations. All these molecular
      interactions are discussed with relevance to the difference between non-curable,
      mostly adult tumors, and curable, mostly paediatric tumors.

PMID- 8869936
TI  - Multiple myeloma, high-dose treatment and autologous stem cell transplantation-
      current status.
AB  - High-dose chemo-radiotherapy with autologous stem cell transplantation (ASCT) has
      introduced the concept of complete remission for multiple myeloma, and can
      improve survival and life quality for selected groups of myeloma patients. A
      number of prognostic factors have been identified, where ASCT in early disease,
      i.e. as part of front-line treatment, seems to be of particular importance for a
      favourable outcome. Even so, most myeloma patients will not be cured by high-dose
      therapy, but new strategies such as repeated autografting and post-graft alpha
      interferon maintenance treatment seem to add additional advantages with respect
      to survival and freedom of disease progression. The technical development has
      enabled efficient in vitro myeloma cell depletion of the autograft as well as
      highly sensitive detection of minimal residual disease after treatment, but the
      clinical significance of these issues remains to be determined, and this question
      is addressed in ongoing gene marking studies. The application of novel
      therapeutic principles, e.g. gene therapy and immunotherapy, might further
      ameliorate the outcome for patients with multiple myeloma.

PMID- 8869937
TI  - Stem cell factor (SCF) synergizes with megakaryocyte colony stimulating activity
      in post-irradiated aplastic plasma in stimulating human megakaryocytopoiesis.
AB  - Plasma obtained from lethally irradiated animals contains a megakaryocyte (MK)
      growth factor which has recently been identified as the ligand for the c-mpl
      receptor and has been named thrombopoietin (TPO). We demonstrate that post
      irradiation aplastic canine plasma (PICS-J) and plasma from a human subject (ML)
      who was accidentally exposed to lethal irradiation, contain high levels of this
      activity, which support both MK proliferation and maturation in a dose-dependent
      manner. These plasma were far more active in stimulating human MK colony
      formation than other types of thrombocytopenic plasma or a number of exogenously
      added human recombinant cytokines and their combinations. The addition of stem
      cell factor (SCF), which alone has a minimal stimulatory affect, to post lethal
      irradiation plasma provided a synergistic stimulation of megakaryocytopoiesis
      both in colony assays and liquid cultures. In colony assays, the combination of
      SCF with PICS-J or ML almost doubled the number of burst forming units (BFU-MK)
      and provided a 1.5-fold increase in colony forming units (CFU-MK). A 1.6-fold
      increase in the number of CD34+ BM cell-derived MK colonies was also elicited. In
      liquid cultures, the presence of both SCF and PICS-J or ML induced the appearance
      of a high proportion of CD34+ (6.56% vs 0.6% control) and CD41+ (3.5% vs 1.2%
      control) cells after 3 days in culture. By day 10, 66.8 x 10(4) CD41+ cells and
      29.8 x 10(4) CD34+ cells were derived from 2 x 10(6) BMMC originally seeded. We
      propose that these unique plasma, which do not contain elevated level of IL-6, IL
      3, GM-CSF, IL-1 beta, erythropoietin or SCF, probably contain high levels of TPO.
      The addition of SCF to the post-irradiation plasma provides a synergistic
      stimulation of megakaryocytopoiesis which may become relevant for future clinical
      application.

PMID- 8869939
TI  - Infections in neutropenic patients. II: Management.
AB  - Improvement in supportive care including the introduction of new antibiotics,
      antiviral and antifungal agents and haematopoietic growth factors have all
      contributed to a decreased chemotherapy-related mortality and morbidity in cancer
      patients. However, infection during neutropenia is still a major complication and
      a great concern for the clinician responsible for the patient. Management of
      infectious complications in the neutropenic patient is reviewed.

PMID- 8869940
TI  - Volume regulation in brain cells: cellular and molecular mechanisms.

PMID- 8869941
TI  - Effects of hyperammonemia on brain protein kinase C substrates.

PMID- 8869938
TI  - Efficacy and toxicity of radiation in preparative regimens for pediatric stem
      cell transplantation. II: Deleterious consequences.
AB  - There has been a dramatic improvement in the treatment of both allogeneic and
      autologous stem cell transplants, especially in children and young adults.
      However, attempts to apply more intensive conditioning treatments to the more
      refractory pediatric malignancies have also increased the risks of deleterious
      consequences. This review examines the risks, and reports important variations in
      the toxic effects of using different conditioning techniques.

PMID- 8869942
TI  - Chronic alcoholism in the absence of Wernicke-Korsakoff syndrome and cirrhosis
      does not result in the loss of serotonergic neurons from the median raphe
      nucleus.
AB  - Previous studies have identified alcohol, thiamine deficiency and liver disease
      as contributing to the neuropathology of alcohol-related brain damage. In order
      to examine the effects of alcohol toxicity and thiamine deficiency on
      serotonergic neurons in the median raphe nucleus (MnR), alcoholic and previously
      published Wernicke-Korsakoff syndrome (WKS) cases without liver disease, were
      compared with age-matched non-alcoholic controls. While there was no difference
      between the estimated number of serotonergic neurons in either controls or
      alcoholics without WKS (means of 63,010 +/- 8,900 and 59,560 +/- 8,010
      respectively), a substantial loss of serotonergic neurons was previously found in
      WKS cases (mean of 19,050 +/- 13,140). Further analysis revealed a significant
      difference in the maximum daily alcohol consumption between these groups.
      However, analysis of covariance showed that the number or serotonergic neurons in
      the MnR did not correlate with the amount of alcohol consumed. Therefore, our
      results suggest that cell loss in the MnR can be attributed to thiamine
      deficiency rather than alcohol per se.

PMID- 8869943
TI  - Contrasting effects of thioacetamide-induced liver damage on the brain uptake
      indices of ornithine, arginine and lysine: modulation by treatment with ornithine
      aspartate.
AB  - The dibasic amino acids arginine (ARG), ornithine (ORN) and lysine (LYS) are
      transported by a common saturable transporter (system gamma +) at the blood-brain
      barrier (BBB). In the present study we compared the brain uptake index (BUI) for
      radiolabelled ORN, ARG and LYS in control rats and in rats treated with
      thioacetamide (TAA) to induce hepatic encephalopathy (HE). Some animals received
      i.v. ornithine aspartate (OA), a drug structurally related to the gamma +
      substrates that ameliorates neurological symptoms following liver damage by
      improving detoxification of ammonia in peripheral tissues: the compound was
      administered either by continuous infusion for 6h at a concentration of 2 g/kg
      (final blood concentration ranging from 0.19-0.5 mM), or as a 15 sec. bolus
      together with the radiolabelled amino acids, at a concentration of 0.35 mM. TAA
      treatment resulted in a delayed and progressive increase of BUI for ORN, to 186%
      of control at 7d post-treatment and to 345% of control at 21d post-treatment,
      when despite sustained liver damage, HE symptoms were already absent. In
      contrast, the BUI for ARG decreased to 30% of control at 7d post-treatment and
      remained low (42% of control) at 21d post-treatment. A 6h infusion of OA to
      untreated rats resulted in a reduction of the BUI for ARG and ORN to 51% and 62%
      of the control levels, respectively. Reductions of a similar magnitude were noted
      with both amino acids following the 15 sec OA bolus, indicating direct
      interaction of OA with the transport site in both cases. OA administered by
      either route abolished the enhancement of BUI for ORN, but did not further
      inhibit the BUI for ARG in the TAA-treated animals. The results indicate that
      some as yet unspecified factors released from damaged liver either modify the
      structure or conformation of the gamma + transporter at the BBB from the normally
      ARG-preferring to the ORN-preferring state, or activate (induce) a different
      transporter specific for ORN which is normally latent.

PMID- 8869944
TI  - Methylmalonic and malonic aciduria in a dog with progressive encephalomyelopathy.
AB  - A 12 week old female Labrador retriever dog with signs of progressive diffuse
      degeneration of the brain and spinal cord was found to have methylmalonic and
      malonic aciduria. Over a 5 month period, the dog developed neurologic signs
      compatible with disease of the central nervous system with predominant diffuse
      cerebral and right lateralizing brainstem deficits. Gross pathological
      examination of the brain showed that the lateral, third, and fourth ventricles of
      the brain were markedly enlarged and associated with white and grey matter
      atrophy. Syringomyelia and hydromyelia of the central canal into the dorsal
      funiculus of the spinal cord beginning at the level of the cervical intumescence
      and extending to the lumbar intumescence was also present. Significant
      biochemical abnormalities include methylmalonic and malonic aciduria, mild lactic
      and pyruvic aciduria. There was also accumulation of citric acid cycle
      intermediates including succinic, aconitic, and fumaric acids. Disordered fatty
      acid oxidation was suggested by increased excretion of adipic, ethylmalonic,
      suberic and sebacic acids. Neither ketoacidosis nor hyperammonemia were present,
      and serum cobalamin levels were normal. Overall, this dog demonstrates an inborn
      error of metabolism resulting in abnormal organic acid accumulation associated
      with a neurodegenerative disease.

PMID- 8869946
TI  - Acute effects of L-tryptophan on brain extracellular 5-HT and 5-HIAA levels in
      chronic experimental portal-systemic encephalopathy.
AB  - Portal-systemic encephalopathy (PSE) is associated with increased brain turnover
      of serotonin (5-hydroxytryptamine; 5-HT). Despite this metabolic increase,
      neuronal release of 5-HT is unaltered in neocortex of portacaval shunted (PCS)
      rats. In the present study, frontal neocortical extracellular 5-HT and 5
      hydroxyindole-3-acetic acid (5-HIAA) levels were determined in PCS rats and sham
      operated controls prior to, as well as, after acute challenge with L-tryptophan
      (L-TRP; a bolus dose of 280 mg/kg i.p. followed by 5 consecutive hourly doses of
      50 mg/kg). Neither basal 5-HT nor 5-HIAA extracellular levels were significantly
      altered in PCS rats compared to controls. L-TRP administration resulted in
      unaltered extracellular 5-HT but elevated 5-HIAA levels in PCS and sham rats.
      These findings do not suggest that changes in brain neuronal 5-HT release play
      any major functional role in the pathogenesis of chronic PSE. The present data
      also emphasize the importance of distinguishing between brain 5-HT metabolism and
      brain 5-HT release.

PMID- 8869945
TI  - MR imaging and spectroscopy of the basal ganglia in chronic liver disease:
      correlation of T1-weighted contrast measurements with abnormalities in proton and
      phosphorus-31 MR spectra.
AB  - The purpose of this study was to correlate the hyperintensity in the globus
      pallidus seen on T1-weighted magnetic resonance imaging (MRI) of the brain in
      chronic liver disease with changes in metabolite ratios measured from both proton
      and phosphorus-31 magnetic resonance spectroscopy (MRS) localised to the basal
      ganglia. T1-weighted spin echo (T1WSE) images were obtained in 21 patients with
      biopsy-proven cirrhosis (nine Child's grade A, eight Child's grade B and four
      Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment
      on clinical, psychometric and electrophysiological testing, four showed evidence
      of subclinical hepatic encephalopathy and 13 had overt hepatic encephalopathy.
      Signal intensities of the globus pallidus and adjacent brain parenchyma were
      measured and contrast calculated, which correlated with the severity of the
      underlying liver disease, when graded according to the Pugh's score (p < 0.05).
      Proton MRS of the basal ganglia was performed in 12 patients and 14 healthy
      volunteers. Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and
      N-acetylaspartate relative to creatine (Cr) were measured. Significant reductions
      in mean Cho/Cr and elevations in mean Glx/Cr ratios were observed in the patient
      population. Phosphorus-31 MRS of the basal ganglia was performed in the remaining
      nine patients and in 15 healthy volunteers. Peak area ratios of phosphomonoesters
      (PME), inorganic phosphate, phosphodiesters (PDE) and phosphocreatine relative to
      beta ATP (ATP) were then measured. Mean values of PME/ATP and PDE/ATP were
      significantly lower in the patient population. No correlation was found between
      the T1WSE MRI contrast measurements of the globus pallidus and the abnormalities
      in the metabolite ratios measured from either proton or phosphorus-31 MR spectra.
      Our results suggest that pallidal hyperintensity seen on T1WSE MR imaging of
      patients with chronic liver disease is not related to the functional
      abnormalities of the brain observed in hepatic encephalopathy.

PMID- 8869947
TI  - The role of human papillomavirus in anogenital cancer.
AB  - More than 30 types of HPV infect the anogenital skin and mucosa, causing
      condylomas and intraepithelial neoplasia of different severity. On a worldwide
      basis, HPV 16, 18, and 45 are distinguished by a strong association with high
      grade intraepithelial neoplasia and the greatest prevalence in anogenital
      malignancy. Genetic experiments have assigned oncogenic activity to the viral
      genes E6, E7, and E5. The encoded proteins interact with and disturb the
      physiologic functions of cellular proteins that are involved in cell cycle
      control. The proteins of HPV 16, 18 or related types are most efficient in this
      regard. Some of these activities lead to genetic instability of the persistently
      infected human cell. This enhances the probability of mutations in cellular proto
      oncogenes and tumor suppressor genes and thus contributes to tumor progression.
      Mutations in cellular genes devoted to the intracellular surveillance of HPV
      infections, integration of viral DNA, and deletions or mutations of viral
      transcription control sequences lead to a significantly increased expression of
      the E6/E7 genes, which is a consistent characteristic of high-grade
      intraepithelial neoplasia and cancers. The genetic instability caused by viral
      oncoproteins and the autocatalytic increase in oncoprotein expression caused by
      mutations in the viral and cellular genome identify the virus as a major driving
      force of progression.

PMID- 8869948
TI  - Epidemiology of anogenital warts and cancer.
AB  - The epithelial lining of the anogenital tract is the target for infection by a
      group of mucosotropic viruses, the HPVs. Clinical or subclinical, transient or
      persistent, HPV infections are among the most common sexually transmitted
      diseases. The prevalence of genital HPV infection among sexually-active
      asymptomatic women is 20% to 40%, using amplified or non-amplified DNA
      hybridization methods to detect the virus. There are more than 70 HPV types
      defined on the basis of DNA homology, of which nearly 30 infect the anogenital
      tract. HPV infection is the direct cause of anogenital warts and a precursor
      event in the genesis of cervical cancer and other anogenital malignant tumors.
      Other HPV types commonly associated with anogenital warts are, for the most part,
      of low oncogenic risk.

PMID- 8869949
TI  - Immunologic responses to human papillomavirus infection.
AB  - The immune mechanisms following papillomavirus infections are barely
      characterized. However, the association of serum antibodies to HPV proteins with
      HPV-related diseases is now well-established. Antibodies to some early viral
      proteins but also to virus capsids (as measured by using VLPs) are found in a
      significant proportion of patients with benign and malignant HPV-related
      diseases. A small number of patients, however, are devoid of detectable
      antibodies. It is not clear whether the missing immune response is of any
      biologic significance for the patient or merely reflects differences in antigen
      presentation during the course of infection. Clearly, the relatively low
      sensitivity of serologic assays renders them unsuitable for diagnostic purposes.
      However, certain combinations of assays may reach a higher predictive value, and
      hence a particular disease may be diagnosed by a pattern of positive (and
      negative?) reactions. The humoral immune response in patients with subclinical
      infections is less well characterized, but such studies are currently being
      performed in different laboratories.

PMID- 8869950
TI  - The role of exfoliative cytology and histopathology in screening and triage.
AB  - The role of cytology in cervical cancer screening is rapidly evolving. Widespread
      implementation of The Bethesda System with its accompanying atlas has provided
      uniform terminology and criteria for reporting cervical pathology. The
      development of new methods for preparing cytologic specimens as well as many
      other screening techniques suggests that current practices may be modified in the
      near future. The implementation of these new approaches may permit more
      conservative management of women with self-limited lesions related to HPV
      exposure, improve detection of serious cancer precursors, and provide more cost
      effective cervical cancer screening.

PMID- 8869951
TI  - New adjunctive methods for cervical cancer screening.
AB  - The sensitivity of cytology for detection of cervical intraepithelial neoplasia
      (CIN) is effectively augmented by cervicography with the disadvantage of lower
      specificity. However, the combination of cytology and cervicography can decrease
      the number of recalls, biopsies, and unnecessary treatments, which reduces cost.
      Down-staging of invasive cancer by visual inspection seems a cost-effective
      alternative to the introduction of cytology in countries with limited health
      facilities. Other methods such as speculoscopy, polarprobe, laser-induced
      fluorescence, computerized digital imaging colposcopy, or computer imaging have a
      potential to be used for future screening or triaging; however, so far,
      insufficient data are available to evaluate the validity of these techniques.

PMID- 8869953
TI  - Recurrent respiratory papillomatosis.
AB  - Recurrent respiratory papillomatosis is an uncommon clinical disorder of the
      respiratory epithelium caused by HPV. It shares an identical viral etiology with
      genital condyloma and, in all likelihood, is transmitted at the time of birth
      (juvenile onset RRP) or through intimate sexual contact (adult onset RRP).
      Despite the precision of the surgical laser under magnification of the operating
      microscope, a substantial proportion of patients with RRP, adults as well as
      pediatric, require repeated operations at frequent intervals because of severe
      hoarseness and upper airway obstruction. For the management of at least a subset
      of patients, the efficacy of adjuvant agents (interferon is a leading choice)
      should be investigated in a multi-institutional clinical trial. For the potential
      prophylactic benefit, cesarean sections in selected high-risk expectant mothers
      should be considered.

PMID- 8869952
TI  - Genital HPV infections in children and adolescents.
AB  - Major differences in estrogen and progesterone levels and in vaginal/cervical
      cell types exist among children, adolescents, and adults, which may help explain
      the observed differences in the prevalence of HPV among these groups. Although
      sexual transmission occurs in both children and adolescents, the persistence of
      genital HPV in the neonate from maternal transmission is highly questionable. The
      discordances in HPV types between neonatal transmission studies and the studies
      in older children have yet to be explained. Neonatal infections seem to be
      predominantly types 16 and 18 and persist for short periods in the genital area.
      The majority of condylomatous lesions in children are HPV types 6 and 11.
      Acquisition of HPV during childhood and adolescence is not an immediate cause of
      severe morbidity. However, significant evidence suggests that early exposure not
      only hastens the development of anogenital cancers but may also increase the
      actual risk of cancer. Future studies should include large-scale longitudinal
      designs to test and follow neonates with careful attention to sexual abuse issues
      during the prospective period so that we may confidently diagnose and
      appropriately treat children with HPV infections. The role of age and immunity
      remains confusing, supporting the need for studies to examine cervical immunity
      more closely.

PMID- 8869954
TI  - Molecular methods for the detection of human papillomavirus infection.
AB  - HPVs are small DNA tumor viruses with an icosahedral virion structure. All
      members of the genus cause diverse benign lesions, and some members promote the
      development of carcinoma. The viruses do not replicate in culture without
      extraordinary measures, and virtually all studies to date have used molecular
      methods to elucidate their biology and natural history. Tests of choice for
      detecting HPV from clinical specimens are based on nucleic acid probe technology.
      Until recently, most epidemiologic and molecular studies employed Southern blot
      (SB), dot blot (DB), and in situ hybridization (ISH). With the exception of ISH,
      which continues to have many uses and a strong following in the pathology
      community, SB and DB have been essentially replaced by polymerase chain reaction
      (PCR) and the Hybrid Capture System (HCS). These newer in vitro probe tests have
      proven to be accurate and robust workhorses for epidemiologic and clinical use.
      Automation promises to revolutionize HPV testing in the near future and will
      allow cost-effective mass screening worldwide.

PMID- 8869955
TI  - Deadly human parasite discovered.

PMID- 8869956
TI  - Leukemia Society of America testifies on FDA reform.

PMID- 8869957
TI  - The role of PSA in the radiotherapy of prostate cancer.
AB  - Pretreatment prostate-specific antigen (PSA) level is the single most important
      prognostic factor for patients undergoing radiotherapy for clinically localized
      prostate cancer. When combined with Gleason score and T-stage, pretreatment PSA
      enhances our ability to accurately predict pathologic stage. Patients with
      pretreatment PSA levels > 10 ng/mL are at high risk for biochemical failure when
      treated with conventional radiation alone. A PSA nadir of > 1 ng/mL and a post
      treatment PSA > 1.5 ng/mL are associated with a high risk of biochemical failure.
      Postoperative radiotherapy delivered while the tumor burden is low (eg, PSA < 1
      ng/mL) predicts a favorable outcome. Many of these conclusions about the
      usefulness of pretreatment PSA are based on the assumption that PSA can be used
      as a surrogate end point for disease-free and overall survival from prostate
      cancer. However, this assumption still remains to be validated by phase III
      trials.

PMID- 8869958
TI  - Average charges for a radical prostatectomy and a transurethral resection of the
      prostate (TURP): geographic variations, 1994.

PMID- 8869959
TI  - Clinical trials referral resource. Clinical trials in the CNS Consortia.

PMID- 8869960
TI  - Combinations of hormones and local therapies in locally advanced prostate
      carcinoma.
AB  - Locally advanced adenocarcinoma of the prostate (American Urological Association
      stages B2, C; American Joint Committee on Cancer stages T2c, T3) has been
      difficult to control by either external-beam irradiation or radical
      prostatectomy. The combination of local therapies with hormonal manipulation is
      an innovative strategy to combat this entity. Hormonal regimens have evolved to
      include total androgen suppression, or maximal androgen blockade. In phase III
      trials, it appears that the combination of irradiation and hormones is superior
      to the use of radiotherapy alone. Results of phase III trials comparing surgery
      to combinations of surgery and hormones have been less encouraging. To date, no
      prospective randomized trial comparing the combination of hormones plus surgery
      to hormones plus irradiation has been completed.

PMID- 8869961
TI  - Detection of nodal micrometastases in head and neck cancer by serial sectioning
      and immunostaining.
AB  - We investigated the incidence of micrometastases from squamous cell carcinomas of
      the head and neck in neck dissection specimens originally staged as pNO. A total
      of 76 dissection specimens from 60 patients were evaluated using serial
      microscopic sectioning in 10-microns intervals, H & E staining, and
      immunostaining with an antibody to pan-cytokeratin. Examination of 1,020 lymph
      nodes from 76 neck dissection specimens revealed 8 micrometastases (7.9%) in 6
      specimens from 6 patients with oral and pharyngeal primaries, resulting in
      upstaging. Six micrometastases were located in lymph nodes 3 to 6 mm in diameter.
      The surgeon should be aware of the relatively high incidence of micrometastases
      from oral and pharyngeal carcinomas, which are undetectable preoperatively or by
      routine histopathologic examination. Primary tumor site (oral cavity and pharynx)
      and certain features of the primary can delineate a group of patients with a
      higher risk of harboring occult metastases who may benefit from elective
      treatment of the neck.

PMID- 8869962
TI  - Role of sentinel node biopsy in the management of malignant melanoma.
AB  - The use of elective lymph node dissection for intermediate-thickness melanoma has
      remained controversial. The technique of sentinel node biopsy (intraoperative
      lymphatic mapping and selective lymphadenectomy) has been developed in an attempt
      to identify patients who may benefit from an elective node dissection while
      sparing patients without occult metastases the morbidity of an elective
      lymphadenectomy. Current methods of performing a sentinel node biopsy include
      both a dye and radiolabeled technique. Although the accuracy of sentinel node
      biopsy for identifying nodes at risk for occult metastases has been demonstrated,
      a survival benefit from dissection of nodal basins that contain occult metastases
      remains to be determined. This article reviews the basis for, technical
      considerations of, and surgical results with selective lymphadenectomy in an
      attempt to clarify the role of this modality in the management of patients with
      cutaneous melanoma.

PMID- 8869963
TI  - Gut reaction: new locale for antibody activity.

PMID- 8869964
TI  - Study advocates breast ultrasound screening as an adjunct to mammography.

PMID- 8869965
TI  - Antitumor activities of combined treatment with a novel immunomodulator,
      (2S,3S,4R)-1-O-(alpha-D-Galactopyranosyl)-2-(N-Hexacosanoylamino)-1,3,4 -
      octadecanetriol (KRN7000), and radiotherapy in tumor-bearing mice.
AB  - The novel immunomodulator (2S,3S,4R)-I-O-(alpha-D-galactopyranosyl)-2- (N
      hexacosanoylamino)-1,3,4-octadecanetriol (KRN7000) in combination with high-dose
      (20 and 30 Gy) local x-ray irradiation or low-dose (3 Gy) fractionated whole-body
      irradiation showed significantly stronger antitumor activities against Meth A-and
      Colon26-bearing mice than treatments by radiation or KRN7000 alone, and 60% of
      mice in combination treatment groups were cured. Furthermore, the results of
      tests rechallenging the cured mice with Meth A and Colon26 cells strongly
      suggested that tumor-specific immunity was induced by the combination treatment.
      The suggestion was supported by the result that the systemic administration of
      KRN7000 could produce large amounts of interleukin-2 and interferon-gamma, which
      contribute to induction of tumor-specific cytotoxic lymphocytes not only in
      normal mice but also in whole-body irradiated mice. Furthermore, it was also
      suggested that KRN7000 contributes to protecting antitumor effector cells, such
      as natural killer cells, from impairments caused by radiation. Taking together
      the results and the knowledge that tumor-specific cytotoxic lymphocytes play a
      critical role in prevention of tumor recurrence and distant metastasis, it is
      strongly suggested that combined therapy with KRN7000 and radiation could be
      quite useful for cancer treatment.

PMID- 8869967
TI  - The antiproliferative effect of trans-retinoic acid is associated with selective
      induction of interleukin-1 beta, a cytokine that directly inhibits growth of lung
      cancer cells.
AB  - Retinoids show promise for prevention and treatment of cancers. In most cases,
      the mechanisms of their anticancer effects are poorly defined, but interactions
      with cytokine genes have been postulated in several systems. The effects of trans
      retinoic acid (RA) on proliferation and cytokine gene expression in the human
      lung carcinoma Lu-CSF-1 are reported. RA exhibited cell-cycle independent
      inhibition of Lu-CSF-1 growth while stimulating endogenous interleukin-1 beta and
      suppressing granulocyte-macrophage colony-stimulating factor and IL-6 mRNAs.
      Reduction in granulocyte-macrophage colony-stimulating factor and IL-6 message
      was associated with reduced RNA stability and was translated into reduced protein
      levels. IL-1 beta mRNA stability was not decreased, and elevation in IL-1 beta
      protein levels was of a comparable magnitude to the increased amounts of its RNA.
      Growth inhibition similar to that following RA treatment could be reproduced by
      exposing cells to exogeneous IL-1 beta alone. These data suggest that changes in
      autologous cytokine gene expression might contribute to growth inhibition of lung
      cancer cells by RA.

PMID- 8869966
TI  - Progressive upregulation of metastasis-related genes in human colon cancer cells
      implanted into the cecum of nude mice.
AB  - We determined whether the upregulation of several metastasis-related genes in
      human colon carcinoma (HCC) cells implanted into the cecal wall of nude mice
      precedes HCC invasion of the muscle layer and subserosa and, ultimately, distant
      metastasis. HCC KM12SM cells were implanted into the subcutis (ectopic) or cecal
      wall (orthotopic). At weekly intervals for up to 6 weeks, cecectomy and resection
      of SC tumors were performed on different groups of mice. Survival and metastasis
      were assessed at 13 weeks. During the first 2 weeks after orthotopic
      implantation, the HCC cells grew progressively in the mucosa and submucosal
      layers of the cecum. By the third week, the cells invaded the muscularis propria
      and then the serosa. All mice undergoing cecectomy at weeks 1 and 2 were cured,
      whereas those undergoing cecectomy at later weeks were not. In situ hybridization
      analysis for expression of several metastasis-related genes-epidermal growth
      factor receptor (EGF-R), basic fibroblast growth factor (bFGF), collagenase type
      IV, and E-cadherin-revealed that the expression level of EGF-R, bFGF, and
      collagenase type IV in the early cecal tumors was low but increased just before
      invasion of the muscularis propria. At all times, the level of gene expression in
      the cecal tumors was higher than in the SC tumors. In contrast, the expression
      level of E-cadherin remained constant and did not differ between tumors in
      ectopic or orthotopic organs. The data suggest that the upregulation of some
      metastasis-related genes precedes tumor cell invasion and production of
      metastasis.

PMID- 8869968
TI  - Reference listings in cancer research.

PMID- 8869969
TI  - Differential expression of immunoreactive HLA-DR and ICAM-1 in human cultured
      orbital fibroblasts and orbital tissue.
AB  - Intercellular adhesion molecule-1 (ICAM-1) and class II major histocompatibility
      complex antigens (MHC II, HLA-DR), are two cell-surface ligands known to be
      critical to the initiation and propagation of immune-mediated inflammation. Their
      expression in tissue is induced by proinflammatory mediators, principally
      interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. We
      examined human orbital fibroblasts and intact human orbital tissue exposed to
      these mediators for the presence of immunoreactive ICAM-1 and HLA-DR antigen.
      These ligands were detectable on stimulated fibroblasts and on fibroblasts and
      vascular endothelium in samples of orbital fat and muscle. ICAM-1 reactivity was
      diffuse and occurred in response to all three proinflammatory mediators. In
      contrast, HLA-DR reactivity was intense but limited to fewer numbers of cells.
      Our results, demonstrating the differential expression of these two ligands, may
      help further to elucidate the underlying pathogenetic mechanisms involved in the
      initiation and perpetuation of immune-mediated orbital inflammatory diseases.

PMID- 8869970
TI  - Extracranial optic canal decompression: indications and technique.
AB  - Optic canal decompression may be beneficial in cases of indirect optic nerve
      trauma, with or without canal fracture. Although no definitive data exist to
      clarify its role, several clinical series have reported on optic canal
      decompression for the treatment of intracanalicular optic nerve trauma, providing
      only limited information of the details of the procedure. We describe extradural
      optic canal decompression using a transethmoidal/transorbital approach. Removal
      of > 180 degrees of the bony canal is possible with this method. The technique
      can be accomplished by orbital surgeons familiar with orbital apical anatomy and
      orbital microsurgery. Experience with cadaver dissection of the orbital apex and
      cadaver surgery may be useful in that it provides confidence for the surgeon
      operating in this critical region. Careful exposure, microscopic visualization,
      delicate technique, and thorough anatomic knowledge minimize the risk of
      complications such as carotid artery penetration or dural laceration.

PMID- 8869971
TI  - Anterior clinoid mucocele masquerading as retrobulbar neuritis.
AB  - Mucoceles arising from the anterior clinoid is rare. Although intrinsically
      benign, mucoceles in the sphenoid sinus (anterior clinoid variant) can lead to
      complications due to their proximity to other structures. We present a case of a
      young man whose visual complaints were typical for retrobulbar optic neuritis.
      Results of radiologic tests for diagnosis led us to the early detection of a
      surgically treatable condition, a sphenoid sinus mucocele (anterior clinoid
      variant). Early surgery was helpful in ameliorating the symptoms, leading to full
      recovery of visual function. The clinician should be aware of this rare entity
      with its presentation in a wide variety of signs and symptoms.

PMID- 8869972
TI  - Juvenile ossifying fibroma of the orbit.
AB  - Juvenile ossifying fibroma is an osseous tumor encased in a sclerotic shell. We
      report findings of juvenile ossifying fibroma in the orbit of a six-year-old boy.
      The bony aspects of this tumor may be suspected on physical examination. Magnetic
      resonance imaging was not helpful in the diagnosis of this fibroma. In fact, the
      technology was misleading because it did not define clearly the bony aspects of
      the tumor. In this case, the less costly computerized tomography revealed the
      bony encasement of the tumor and best defined the borders. With the trend in
      health care of cost containment, it may be that computerized tomography is the
      appropriate primary imaging study for some suspected orbital tumors based on
      thorough clinical examination.

PMID- 8869973
TI  - Laser Doppler perfusion imaging of eyelid skin.
AB  - We report an initial laser Doppler perfusion study of the eyelids and compare the
      results with those of other cutaneous regions. Eleven healthy subjects with no
      prior medical or surgical history, or eyelid malposition underwent laser Doppler
      perfusion scanning of six skin locations: right forearm, right middle fingertip,
      right upper eyelid, right lower eyelid, left upper eyelid, and left lower eyelid.
      Cutaneous perfusion in the four eyelid locations and right middle fingertip were
      statistically similar to each other but significantly higher than that in the
      right forearm (p = 0.002). Also, mean perfusion in pretarsal skin was > 50% than
      that in preseptal skin (p = 0.002). In addition, in an eyelid with
      histopathologically documented basal cell carcinoma, cutaneous perfusion was
      significantly higher than the mean of the normal eyelids (p = 0.002). Eyelids are
      perfused at the same high rate as are other regions of the head, and
      significantly higher than low flow regions, such as the extremities. Future
      application of this laser Doppler perfusion scanning include assessing burn
      depth, postoperative monitoring of periorbital tissue transfer, distinguishing
      benign and malignant adnexal skin lesions, and establishing the pathologic
      margins of lid tumors.

PMID- 8869974
TI  - Divided nevus of the eyelid: a case report.
AB  - Divided nevus of the eyelid as a rare pathologic entity and develops during fetal
      growth, when the two eyelids are still fused together. Its surgical treatment is
      mostly based on full thickness skin grafts. We report a case of a 22-year-old
      woman with a congenital divided nevus affecting the left upper and lower eyelid.
      The patient was treated in our Department because of the onset of a purple red
      nodule in the lower part of the nevus. We examined the case from embryological,
      histopathological, clinical, and diagnostic standpoints, and discuss surgical
      options in order to reach an optimal functional and aestetic result.

PMID- 8869975
TI  - The role of cytology in the diagnosis of periocular basal cell carcinomas.
AB  - The accurate diagnosis of eyelid tumors such as basal cell carcinoma (BCC)
      requires histological confirmation, usually obtained by biopsy. Cytology provides
      a rapid alternative that can yield a diagnosis during the initial outpatient
      appointment. The accuracy of this technique has been reported to be very good but
      its sensitivity in the diagnosis of periocular lesions is unknown. In order to
      assess the accuracy of cytology in eyelid lesions suspected clinically to be
      BCCs, the cytological and histopathological diagnoses were compared
      retrospectively in 20 lesions from 17 consecutive patients who underwent cytology
      followed by excision biopsy. The sensitivity of cytology for the diagnosis of BCC
      was 92% compared with 88% for the diagnosis of malignant tumor. The predictive
      accuracy was 75% for either diagnosis. This was compared with a second group of
      26 clinical BCCs from 22 consecutive patients who had incisional biopsy and
      histological examination followed by excision with histological confirmation, in
      which case the sensitivity was 100% and accuracy 96%. It was concluded that
      cytology was sufficiently accurate to plan excision and reconstructive surgery,
      when a confirmatory tissue diagnosis can be made, but not sufficiently sensitive
      for conservative regimens such as radiotherapy because of the small risk of false
      negative diagnoses.

PMID- 8869976
TI  - Bilateral tumor-like invasive xanthelasma palapebrarum in the superior palpebra.
AB  - We describe a very rare case of bilateral xanthelasma. Pathologically, xanthoma
      cells invaded the dermis, subcutaneous tissues, orbicularis muscle, orbital
      septum, orbital fat, and palpebral levator. Clinically, diplopia was present.
      Although considerable improvement was noted in appearance after surgical removal
      of as much of the tumors as possible, an increase in and a recurrence of the
      remaining tumors were observed at a later date following the operation.

PMID- 8869977
TI  - Cystic lesions of the extraocular muscles.
AB  - Cystic lesions of the extraocular muscles (EOMs) are uncommon. Six patients with
      a cystic lesion in an extraocular muscle, as observed by computerized tomography
      (CT) scanning, were retrospectively identified from the practice of one of the
      authors (G.C.S.), and their clinical course was reviewed. All the patients were
      treated initially with oral corticosteroids. Those who did not respond to this
      therapy underwent surgical exploration. Four patients demonstrated complete
      resolution of clinical signs and symptoms with oral steroid therapy.
      Posttreatment CT scans performed in two of these patients showed resolution of
      the cystic lesion with residual muscle thickening in one. The two patients not
      responding to steroids underwent surgical excision and histopathology confirmed
      the diagnosis of cysticercosis. Cysticercosis is a previously reported cause of a
      cystic lesion in an EOM. To the best of our knowledge, cystic lesions of the EOMs
      resolving with steroids have not been previously reported. Response to oral
      steroids in four of our patients is suggestive of myositis with a cystic change
      in the muscle. We recommend a trial of oral steroid therapy in patients with a
      cystic EOM lesion before surgical exploration is performed.

PMID- 8869978
TI  - Combined paresis and restriction of the extraocular muscles after orbital
      fracture: a study of 16 patients.
AB  - Sixteen patients with combined paresis and restriction of extraocular muscle(s)
      orbital fracture repair were studied before and after in order to determine the
      clinical features and management of such patients. All 16 patients showed limited
      ductions of the involved eye in the field of action of the entrapped, paretic
      muscle and of the antagonist muscle after orbital fracture. Single extraocular
      muscles (13 patients) and two extraocular muscles (three patients) were
      demonstrated adjacent to the fracture site on orbital computed tomography (CT).
      In three patients prior to orbital surgery, a deviation in primary position was
      present. After fracture repair with release of the entrapped muscle in all
      patients, evidence of paresis of the muscle was demonstrated by underaction in
      its field of action and overaction in the field of its antagonist. There was a
      resultant manifest tropia or phoria in the primary position. In seven patients,
      the paresis gradually improved with no tropia and little diplopia in the
      functional fields of gaze. Three patients had minimal deviations and required no
      further treatment. Six patients with significant deviations required prisms
      (three patients) or strabismus surgery (three patients). The latter three
      patients had two muscles involved. Results of this study demonstrate that the
      ophthalmologist must appropriately diagnose patients with paresis and restriction
      of an extraocular muscle and counsel them that "new" diplopia may occur after
      orbital fracture repair and that this diplopia may require additional therapy.

PMID- 8869979
TI  - Holmium laser canaliculoplasty.
AB  - Thirty canaliculi of 18 patients with complete or nearly complete canalicular
      obstruction were subjected to laser canaliculoplasty as a substitute for the
      standard Jones-type bypass conduct. Etiologies for the obstruction included
      congenital lacrimal system atresia, eyelid trauma, scarring following previous
      lacrimal surgery, and chronic inflammatory fibrosis. The procedure utilized a
      holmium laser delivered via a 1,000 mu optical fiber to cut a 1-mm channel from
      the punctum into the lacrimal sac. In nine eyes, this procedure was combined with
      a surgical dacryocystorhinostomy (DCR) for concurrent lower nasolacrimal duct
      obstruction. Silicone stents were left in place for 6 months postoperatively.
      Follow-up data were available for 28 canaliculi of 17 patients. Moderate or
      better improvement in symptomatic epiphora and evidence of canalicular patency to
      drainage was seen in 16 of 28 (57%) treated canaliculi, and significant
      improvement was recorded in 12 of 28 (43%). Although these figures are lower than
      those obtainable after repair of small areas of focal canalicular stenosis or
      obstruction, the procedure is superior to any previous attempts at reconstruction
      of extensive obstructions, short of placement of a Jones tube. When successful,
      this procedure offers re-establishment of a near normal physiologic system, and
      avoids the complications of and patient dissatisfaction associated with a Jones
      tube.

PMID- 8869980
TI  - Dog bite-induced canalicular lacerations: a review of 17 cases.
AB  - Canalicular lacerations are frequently found in conjunction with other facial
      lacerations occurring in dog bite injuries. A review of the treatment of 17 dog
      bite-induced canalicular lacerations is presented. Certain pathogens commonly
      found in the canine oral flora may cause severe secondary infections, which may
      result in sepsis and even death. These pathogens are reviewed along with a
      description of appropriate plans for antimicrobial prophylaxis. A surgical
      approach to such injuries is described.

PMID- 8869981
TI  - Acute, unilateral, temporary blepharoptosis: a diagnostic quandry.

PMID- 8869982
TI  - Effect of VDUs on the eyes: report of a 6-year epidemiological study.
AB  - One thousand, three hundred and sixteen office workers [692 visual display unit
      (VDU) users, 624 controls in the first year] were examined once each year over a
      6-year period to establish whether or not VDU work was a factor in the occurrence
      of visual symptoms, ocular abnormalities, or ocular disease. Statistical analysis
      showed that although there were differences between VDU users and nonusers in the
      amount of myopia, the prevalence of some symptoms, and the prevalence of signs of
      fundal or vitreal disease, the differences were small and there were no clear
      trends or patterns to lend convincing support to the hypothesis that VDU work may
      be a risk factor. There were no significant differences in the prevalence and
      incidence of cataract.

PMID- 8869983
TI  - Bacterial contamination of hydrophilic contact lens solutions marketed in spain.
AB  - Bacterial contamination of hydrophilic contact lens solutions may play an
      important role in contact lens-associated ocular infections. This study
      investigated bacterial contamination in 52 different hydrophilic contact lens
      solutions marketed in Spain by 12 different companies. We filtered the entire
      contents of 5 new, factory-sealed bottles from each of the 52 brands and cultured
      the fitter on a neutralizing broth plate. Bacteria were cultured, isolated, and
      identified from 29 of the 260 bottles tested (11.15%). Eight of the 52 brands had
      at least 1 of the 5 bottles contaminated (15.38%). Contaminated solutions
      originated from four different companies. One manufacturer contributed most of
      the positive cases due, presumably, to an industrial contamination by Pseudomonas
      fluorescens. The rest of the culture-positive bottles were contaminated by
      Bacillus spp. and Oerskovia spp.

PMID- 8869984
TI  - The role of context in reading with central field loss.
AB  - It has been suggested that readers with central field loss (CFL) may not be able
      to use context to facilitate reading in the same way that normally sighted
      readers do because their processing capacity is fully utilized decoding the
      degraded visual stimulus. If true, this could account for their slow reading,
      even when text is appropriately magnified. Readers with CFL and normally sighted,
      age-matched controls read sentences and lists of random words from two dynamic
      text displays. We used sentence-gain (the ratio of reading rates for sentences to
      random words) to assess the use of context. Sentence-gain was equivalent across
      groups. Therefore, reduced reliance on context cannot explain the slower reading
      rates of people with CFL.

PMID- 8869985
TI  - Convergence demands by spectacle magnifiers.
AB  - A general equation, c delta = k1b + k2sF, for finding the binocular convergence
      demands by spectacle magnifiers to view images at any distance is presented.
      Factor k1 in the equation yields the accommodative demand to view the image;
      factor k2 determines the actual reduction in convergence demand provided by the
      vendors' incorporation of base-in prism. When magnifiers from virtual images at
      finite distances, such as at the least distance of distinct vision or 25 cm, the
      interpupiliary distance (b), the separation between the lenses and the eyes (d),
      and the distance between the optical centers of the lenses (s) are basic
      quantities, according to this equation. The fundamental datum that the vendors
      should specify is the distance (s) between the optical centers of the lenses,
      rather than base-in prism. The specification of base-in prism is unrellable when
      images are formed at finite distances and the frame PD is not equal to the
      distance IPD. When the image is formed at infinity, that is when the angular
      magnification M = F/4, the convergence demand by spectacle magnifiers only
      depends on the separation between the optical centers of the lenses and the lens
      power, that is, c delta = sF. It is independent of the interpupillary distance
      (b) and the separation between the lenses and the eyes (d). We also present an
      equation, to find the disparity of the accommodative/convergence relation caused
      by spectacle magnifiers. Knowing the demands on convergence and accommodation,
      the practitioner can probably evaluate the potential for successful adaptation to
      spectacle magnifiers from routine measurements of positive and negative relative
      convergence and accommodation.

PMID- 8869986
TI  - Monocular contrast sensitivity in 3- to 36-month-old human infants.
AB  - A recently developed psychophysical "card" technique was used to evaluate
      monocular contrast sensitivity in ninety 3-, 6-, 12-, 24-, and 36-month-old human
      infants. Results showed that for 3-, 6-, 24-, and 36-month-olds, monocular
      contrast sensitivity functions were very similar to binocular contrast
      sensitivity functions estimated in a previous experiment. However, at 12-months,
      monocular contrast sensitivity functions were significantly lower (about 1
      octave) than binocular contrast sensitivity functions, a trend also observed in
      developmental studies of visual acuity. This asymmetry suggests that the neural
      substrate underlying the development of monocular and binocular spatial vision
      undergoes different rates of development, at least during the months surrounding
      the end of the first postnatal year.

PMID- 8869987
TI  - Corneal changes in schoolchildren.
AB  - Videokeratography (TMS-1) data from the right eyes of 788 children between the
      ages of 6 and 14 years, examined in 1994 as part of the Orinda Longitudinal Study
      of Myopia, were analyzed using the Fast Fourier Transform (FFT) to quantify
      corneal power, toricity, and toricity axis. Cross-sectional analysis showed no
      statistically significant age trend for these parameters. Conversely,
      longitudinal analysis of data for 387 of these children, first measured in 1991,
      showed a statistically significant decrease in corneal power. Corneal toricity
      did not change significantly over this 3-year period, although there was a minute
      but statistically significant clockwise axis shift. From this we conclude that in
      the elementary and junior high school years-during which period axial length is
      known to increase-corneal flattening continues, but corneal toricity is stable.

PMID- 8869988
TI  - Low vision and surfing.
AB  - Low vision rehabilitation often concentrates on vocational and living skills
      training. Nonetheless, the motivation for improving reading or travel skills may
      be to pursue some enjoyable recreational activity. A case report of a telescopic
      aid for surfing is presented, emphasizing the importance of recreation in low
      vision rehabilitation.

PMID- 8869989
TI  - Idiopathic peripheral vitreous membranes.
AB  - An unusual case of bilateral prepapillary glial sheets and peripheral vitreal
      membranes is described. Such membranes are seldom reported in the literature. A
      retinal specialist concurred that the avascular membranes, present in the
      inferior retinae of both eyes, were congenital because the membranes were
      bilateral and symmetrical and because the patient had no other sign of retinal or
      systemic conditions associated with membrane formation. There were fenestrations
      in the membranes, which gave the initial impression of retinal tears and
      associated detachment However, there were no retinal breaks beneath the membranes
      nor was there any evidence of retinitis, myopia, or any other mechanism which
      could be considered causative for a vitreal membrane. Diseases associated with
      membrane formation and the confusion of the membranes with retinal detachment are
      discussed.

PMID- 8869990
TI  - Immunoexpression of the alpha subunit of a guanine nucleotide-binding protein
      (Go) in pulmonary neuroendocrine cells and neoplasms.
AB  - The alpha subunit of a GTP-binding protein, Go, was investigated in pulmonary
      neuroendocrine neoplasms and fetal tissues of the lung by an immunohistochemical
      method. Positive immunostaining for the alpha subunit of Go (Go alpha) was found
      predominantly on the cell membrane and found occasionally in the cytoplasm.
      Typical carcinoids were all positively stained (9/9), and small cell carcinoma
      showed weaker and less frequent staining (5 positive cases in 10). Atypical
      carcinoids were variously stained (3/4). The tendency for obvious neuroendocrine
      differentiation to be immunohistochemically determined in typical carcinoids and
      not in small cell carcinoma is also true of staining for neuron specific enolase
      (NSE), chromogranin A (CG-A) and synaptophysin. In the lung, Go alpha
      immunostaining was positive not only in nerve tissues but also in the airway
      epithelium. In the fetal lung, serial sections immunostained for NSE, CG-A and Go
      alpha confirmed that Go alpha-immunoreactive cells belong to the neuroendocrine
      cell population. The biological significance of Go alpha is unclear in normal and
      neoplastic lung tissues, but Go alpha is a useful marker of neuroendocrine cells
      and neoplasma of the lung.

PMID- 8869991
TI  - Kinetics of monocytoid B lymphocytes in localized inflammatory lesions induced by
      lipopolysaccharide in mice.
AB  - Immunohistochemistry was used to study the kinetics of B lymphocytes (B-lys) in
      the early stages of the localized inflammatory response induced in SMA mice by
      the subcutaneous injection of lipopolysaccharide (LPS). At the injection sites,
      medium-sized B-lys formed early inflammatory lesions with neutrophils and
      activated macrophages on days 1 and 2. The B-lys were morphologically similar to
      monocytes, but were not stained with Mac1 antibody. Remarkably the B-lys showed
      the phenotypes of B220+, IgM+, IgD (slight to negative), Ly-1- and CD23- by
      double immunohistochemical staining. The B-lys were also positive for alkaline
      phosphatase. Consequently the B-lys could be identified as monocytoid B-lys or
      marginal zone B-lys. Plasmacytic B-lys and plasma cells were first observed on
      days 3 and 4, but no lymphoid follicles were found at the injection sites. In the
      inguinal lymph nodes, the same B-lys responses were mainly induced in the
      paracortical lesions (T cell areas) preceding the formation of activated germinal
      centers (GC). These findings suggested that the B-lys, induced by injections of
      LPS, matured into plasma cells in the localized inflammatory lesions independent
      of GC, and that they were different from follicular B-lys.

PMID- 8869992
TI  - Neovascularization of the corpus luteum of rats during the estrus cycle.
AB  - In order to elucidate the chronological morphological changes of the corpus
      luteum (CL) of rats, as a physiological angiogenesis model, the CL of rat ovaries
      was studied light microscopically using periodic acid methenamine silver staining
      (PAM) and immunostaining for type IV collagen, laminin, thrombomodulin (TM),
      factor VIII related antigen (factor VIII) and alpha-smooth muscle actin (alpha
      SMA). The CL was also studied electron microscopically. Female Wistar-Imamichi
      rats were used, which have a regular 4-day estrous cycle. The histological
      changes of the CL were observed in 6-hour intervals from 4 h before the ovulation
      to 28 h post-ovulation during the estrous cycle. Once the basement membrane (BM)
      of the follicle disintegrated following ovulation, developing capillaries entered
      into the CL and formed a vascular lumen with a surrounding BM, which showed
      positive for PAM staining, type IV collagen and laminin. The developing
      capillaries in the CL showed a weakly positive reaction for TM and factor VIII,
      but were negative for alpha-SMA. However, the appearance of immature pericytes
      around the well-developed capillary was obvious with electron microscopy. The
      study reported here provides detailed descriptions of angiogenesis during
      luteinization. It is concluded that the angiogenesis of the CL begins at the time
      of destruction of the BM of the ovarian follicle, and that the capillary BM
      appears when the capillary forms its lumen. Moreover, it was demonstrated that
      the capillary does not develop into an arteriole during luteinization.

PMID- 8869993
TI  - Histological grade in invasive ductal carcinoma of breast correlates with the
      proliferative activity evaluated by BrdU: an immunohistochemical study including
      correlations with p53, c-erbB-2 and estrogen receptor status.
AB  - Thirty cases of invasive ductal carcinoma of the breast were classified to
      histological subtype according to the General Rules for Clinical and Pathological
      Recording of Breast Cancer of the Japanese Breast Cancer Society and
      histologically graded using the Nottingham method and the correlation of
      histology with proliferative activity was investigated using bromodeoxyuridine
      (BrdU). In addition, the overexpression of p53 protein, c-erbB-2 oncoprotein and
      estrogen receptor (ER) were immunohistochemically examined in order to discuss
      the relationship with histological subtype and histological grade. Histological
      grade correlated positively to the BrdU labeling index (LI) and overexpression of
      p53. High grade carcinoma demonstrated c-erbB-2 more frequently and exhibited a
      low incidence of ER. However, no significant relationship was found between BrdU
      LI, overexpression of p53 and c-erbB-2 and histological subtype. These results
      suggest that the histological grade does represent the proliferative activity of
      tumor cells and that adding the histological grade to the pathological diagnosis
      in invasive ductal breast carcinoma may be useful from the clinicopathological
      aspect concerning tumor behavior.

PMID- 8869994
TI  - p53 and Ki-67 immunoreactivity and nuclear morphometry of 'carcinoma-in-adenoma'
      and adenoma of the gall-bladder.
AB  - Twenty intramucosal tumors of 'carcinoma-in-adenoma' and 43 adenomas (39 pyloric
      gland type, 4 intestinal type) of the gall-bladder were studied to establish more
      precise histological criteria of carcinoma or adenoma in cases of 'carcinoma in
      pyloric gland type adenoma', to compare carcinoma in adenoma with pure, that is,
      without adenomatous components, carcinoma, and to confirm the benign nature of
      spindle cell foci in the adenomas. Ki-67 and p53 immunostaining and nuclear
      morphometry were used. Eight pure intramucosal cancers were used as controls. The
      formalin-fixed, paraffin-embedded sections were stained with p53 and Ki-67
      antibodies. Spindle cell foci were observed only in the adenoma area of the
      pyloric gland type, with a frequency of 23% in 39 adenomas, and of 45% in 20
      tumors of carcinoma-in-adenoma. Ki-67 staining was negative in 129 of 130 spindle
      cell foci examined, regardless of their size, and positive in only one focus (550
      microns in size, Ki-67 index 0.2%). All of the spindle cell foci were negative
      for p53 stain. The Ki-67 positive index was 36.6 +/- 5.6% in the 8 pure
      carcinomas, and 12.5 +/- 1.9% in the carcinoma area of 16 tumors with carcinoma
      in-adenoma, while it was 7.9 +/- 1.7% and in the adenoma areas of 16 tumors with
      carcinoma-in-adenoma and 4.9 +/- 0.5% in the 32 pure pyloric gland adenomas. The
      p53-protein overexpression was found in seven of eight pure intramucosal cancers,
      and in one of 16 cancer components of carcinoma-in-adenoma. However, it was not
      found in any of 16 adenoma components of carcinoma-in-adenoma, and 35 adenomas.
      Cells of the cancer tissue of carcinoma-in-adenoma showed a significantly larger
      nuclear area and a larger nuclear minor axis than those of the pyloric gland type
      adenomas, as well as other architectural and cytologic abnormalities differing
      from the features of adenomas. These results suggest that clustered spindle cells
      do not indicate a malignant transformation of adenoma cells and that carcinomas
      in carcinoma-in-adenoma are different from pyloric gland type adenomas in terms
      of morphology and proliferative activity. Moreover, the results of the present
      study indicate that carcinomas. In carcinoma-in-adenoma are lower in malignancy
      than pure carcinomas, and that their genetic abnormality may differ from that of
      pure carcinomas.

PMID- 8869995
TI  - Frozen-section services by telepathology: experience of 100 cases in the San-in
      District, Japan.
AB  - The early experience is reported here of the use of intra-operative frozen
      section service by telepathology using the integrated Service Digital Network
      (ISDN), a commercially available system that is being connected between the
      Department of Pathology of Tottori University and Matsue City Hospital, a
      distance of 30 km. The transfer rate is currently 64 kbit/s. The frozen-section
      service was conducted for a total of 117 tissue specimens (organs) from 100
      patients between August 1993 and May 1995. The average time taken for examination
      of each specimen of frozen section was 13 min, ranging between 2 and 42 min. The
      average number of transmitted images was 6.2. Six cases necessitated more than 11
      transmitted images to make a diagnosis, while 13 cases could be diagnosed from
      two images only. Correct and permissible diagnoses were obtained in 109 (93.2%)
      out of 117 specimens when comparing the telepathology diagnosis with that of
      direct microscopy. Improper or misdiagnosis was made for eight cases (specimens),
      which were misinterpreted as papillary carcinoma in Basedow's disease, adenoma
      and hyperplasia in two pheochromocytomas, solid-tubular carcinoma in phyllodes
      tumor, mastopathy in invasive carcinoma, metastatic carcinoma in astrocytoma,
      follicular lymphoma in reactive hyperplasia, and lymphadenitis in follicular
      lymphoma. In retrospect, diagnosis of these cases should have been deferred. From
      the results, it was concluded that the intraoperative frozen-section service by
      telepathology may be a worthwhile substitute for hospitals with limited
      accessibility to local pathology service, in spite of pitfalls in some cases.
      Well prepared, high-quality frozen section, sufficient verbal communication with
      surgeons, and a rather conservative attitude on the part of a well-trained
      pathologist seem to be the essential ingredients for reaching an accurate
      decision when using telepathology.

PMID- 8869996
TI  - Histopathological study of stromal smooth muscle cells in fibroadenoma of the
      breast.
AB  - Smooth muscle cells are extremely rare stromal components of fibroadenoma. Eighty
      five cases of fibroadenoma were reviewed in order to investigate the frequency of
      smooth muscle cells and to discuss its origin. Of the 85 cases, four (4.7%) cases
      showed smooth muscle cells in the stroma. Distribution in terms of age and tumor
      size did not show any difference from other cases. Three cases were classified as
      an intracanalicular subtype, and one was a mastopathic subtype. The cells
      possessed most of the ultrastructural characteristics of smooth muscle cells, but
      poor indentation of nuclear contours suggested the last remnant of fibroblasts.
      It was therefore easy to recognize the cells derived from fibroblasts. In two of
      four cases, smooth muscle cells were observed in the stroma, which had marked
      hyalinization and calcification. Therefore, it was supposed that smooth muscle
      cells could appear in the stroma of long-standing tumors.

PMID- 8869997
TI  - Thymic carcinoma of the thyroid.
AB  - A highly malignant case of intrathyroidal thymic carcinoma showing morphological
      and biochemical evidence identical with mediastinal thymoma is presented. A 32
      year-old female, who had previously undergone total colectomy with ileo
      proctostomy due to familial adenomatous polypnosis, was operated on for a tumor
      (3.4 x 4.5 cm) originating from the left thyroid lobe. A minute focus (diam. 0.8
      cm) of papillary adenocarcinoma also existed in the upper pole of the right lobe.
      The main tumor was morphologically an epithelial thymoma with scanty lymphocyte
      intermixing and showed medullary differentiation with apparent Hassall's
      corpuscles. Mitosis was frequent and numerous tumor thrombi were in the
      subcapsular veins. Five months after the total thyroidectomy and lymph node
      dissection, a subcutaneous recurrence of the tumour (diam. 2.3 cm) appeared in
      the anterior cervical region. The cystic contents of the recurrent tumor revealed
      a high titer of thymosin alpha 1-Other organs, including thymus, lungs, and
      adrenals, had all been free of neoplastic changes clinically and radiologically
      for 5 months after her first admission until the local tumor recurrence.

PMID- 8869998
TI  - Late bone metastasis from an encapsulated follicular carcinoma of the thyroid
      without capsular and vascular invasion.
AB  - A unique case of encapsulated follicular carcinoma of the thyroid, which lacked
      histologic evidence of capsular and vascular invasion but developed a late bone
      metastasis, is described. The thyroid tumor was found in a 42-year-old man. It
      was relatively small (2.5 cm) and totally encapsulated. Histologically, the
      thyroid tumor showed a microfollicular growth pattern of follicular cells and
      revealed no histologic evidence of nuclear atypia, mitotic figures or capsular
      and vascular invasion. The diagnosis of microfollicular adenoma was made and
      partial thyroidectomy was performed. Bone (rlb) metastasis of the thyroid tumor
      developed 22 years after the thyroidectomy. The present case suggested that
      capsular and/or vascular invasion is not always sufficient for the diagnosis of
      encapsulated follicular carcinoma of the thyroid.

PMID- 8869999
TI  - Malignant fibrous histiocytoma of the esophagus.
AB  - A 78-year-old man presented with an esophageal polyp that was confirmed by
      immunohistochemistry and electron microscopy to be malignant fibrous
      histiocytoma. The tumor was comprised of a proliferation of spindle-shaped cells
      admixed with bizarre giant cells. These tumor cells were immunoreactive for
      smooth muscle actin, vimentin, alpha-1-anti-chymotrypsin and CD68. Electron
      microscopic examination revealed the myofibroblastic and histiocytic features of
      the tumor cells. No elements of epithelial or myogenic differentiation were found
      in the tumor. Malignant fibrous histiocytoma of the esophagus is extremely rare,
      with 10 cases being documented so far in the literature. The differential
      diagnosis of pleomorphic tumors of the esophagus is discussed.

PMID- 8870000
TI  - Stromal melanocytosis of an adenoid cystic carcinoma arising from the palatal
      minor salivary gland.
AB  - An unusual case of adenoid cystic carcinoma arising from the palatal minor
      salivary gland in a 63-year-old Japanese female is reported. In addition to the
      characteristic histopathologic features of adenoid cystic carcinoma, spindle- and
      dendritic-shaped cells containing excessive amounts of melanin pigment were
      densely and widely distributed in the stroma resulting in a blue nevus-like
      appearance. Neither melanocytes nor melanin pigments were seen within the
      parenchyma. The possible histogenesis of melanocytes in the stroma of the
      salivary gland carcinoma is discussed, although no firm conclusion could be
      drawn.

PMID- 8870001
TI  - Mycoplasma infection found in a human mesothelial cell line T-85.

PMID- 8870002
TI  - Development and heterogeneity of macrophages and their related cells through
      their differentiation pathways.
AB  - Macrophages are a heterogeneous population differing in their site of location,
      morphology and function. They develop from hematopoietic stem cells originating
      in both fetal and bone marrow hematopoiesis. In yolk sac and early hepatic
      hematopoiesis, primitive/fetal macrophages develop from hematopoietic stem cells,
      bypassing the stage of monocytic cells (monoblasts, promonocytes and monocytes),
      possess proliferative capacity and differentiate into resident macrophages in
      tissues in late ontogeny. Monocytic cells develop in hepatic hematopoiesis after
      the development of primitive/fetal macrophages, then move into the bone marrow in
      late ontogeny, forming a monocyte-derived macrophage population in tissues. Like
      monocytes, the monocyte-derived macrophages have no proliferative potential and
      are short-lived, whereas the resident macrophages are long-lived in tissue,
      possess proliferative capacity and can be sustained by self-renewal. In adult
      life, the bone marrow releases macrophage precursors (immature myeloid cells) and
      monocytes into peripheral blood, but normally not monoblasts or promonocyts. The
      myeloid precursor cells migrate into tissues and differentiate into resident
      macrophages or related cells in situ due to macrophage differentiation or growth
      factors, such as M-CSF and GM-CSF, produced in situ and/or supplied humorally.
      Monocytes, however, migrate into tissues in response to inflammatory stimuli and
      differentiate into exudate macrophages. The distinct differentiation pathways of
      monocyte/macrophages, resident macrophages, other macrophage subpopulations, and
      macrophage-related cells are reviewed together with the heterogeneity of
      macrophage precursor cells.

PMID- 8870003
TI  - Nuclear p53 accumulation by small-sized adenocarcinomas of the lung.
AB  - In order to evaluate the alterations of nuclear p53 accumulation in early stage
      adenocarcinomas of the lung, nuclear p53 accumulation by small-sized peripheral
      adenocarcinomas of the lung was examined immunohistochemically. Peripheral
      adenocarcinomas of the lung, 2 cm or less in diameter, have been classified into
      two groups; one showing replacing growth of the pulmonary alveolar structure and
      the other showing non-replacing growth. The former group has been subdivided into
      three microscopic subtypes: type A, localized bronchioloalveolar carcinoma
      (LBAC); B, LBAC with foci of pulmonary alveolar structural collapse; and C, LBAC
      with foci of active fibroblastic proliferation. Type C is thought to be advanced
      carcinoma, which develops progressively from types A and B. Two of 32 (6%) types
      A and B carcinomas, 37 of 133 (28%) type C carcinomas and 14 of 35 (40%) non
      replacement-type adenocarcinomas showed positive nuclear staining for p53. The
      positive staining frequency was significantly higher for type C than for types A
      and B (P < 0.05). These results suggest that nuclear p53 accumulation occurs in
      the transition from the early to advanced stages of replacement-type
      adenocarcinoma development and it may be a clinically useful indicator of the
      degree of tumor malignancy.

PMID- 8870004
TI  - Localized amyloidosis of the seminal vesicle: identification of lactoferrin
      immunoreactivity in the amyloid material.
AB  - Three specimens of localized amyloidosis of the seminal vesicle surgically
      removed for prostatic cancer were immunohistochemically analyzed to clarify the
      nature of the permanganate-sensitive congophilic subepithelial deposition. A
      variety of known amyloidogenic substances and secretory products in the seminal
      fluid were screened using the indirect immunoperoxidase method. In addition to
      reactivities with antibodies to amyloid P component and human seminal plasma, the
      amyloid material was immunoreactive for lactoferrin using a rabbit antiserum and
      two of three mouse monoclonal antibodies. All the antibodies labeled some of the
      normal seminal vesicle epithelial cells for this ironbinding, bacteriostatic
      glycoprotein. In the prostate without accompanying amyloid deposition, a
      considerable proportion of the glandular epithelium and secretory material were
      positive for lactoferrin. Pre-embedding immunoelectron microscopy showed
      lactoferrin immunoreactivity on the amyloid fibrils. Focal staining of the
      amyloid for gross cystic disease fluid protein-15 was also observed in two
      lesions. These findings strongly suggest that lactoferrin is the major
      constituent in localized senile amyloidosis of the seminal vesicle.

PMID- 8870005
TI  - Lipoleiomyomatous tumors of the uterus: a heterogeneous group? Histopathological
      study of five cases.
AB  - Five surgical cases of lipoleiomyomatous tumor of the uterus were studied
      histopathologically. All the patients were postmenopausal. Three tumors had
      arisen in the corpus, and the remaining two in the cervix. In four of five cases,
      tumors consisted of smooth muscle tissue admixed with varying amounts of mature
      adipose tissue, which did not show cytological atypism. In the remaining single
      case, the tumor contained, in addition to smooth muscle tissue and fibroadipose
      tissue, many anomalous arterial blood vessels, which showed an irregular,
      tortuous appearance resembling that found in renal angiomyolipoma. From the
      histopathological findings and a review of the relevant literature, it was
      considered that lipoleiomyomatous tumor of the uterus is not a single
      histopathological entity but is composed of two distinct neoplasms with different
      histogenesis; that is, 'lipoleiomyoma' and 'anglolipoleiomyoma'. While the latter
      tumor is most likely of a choristomatous nature, the former probably arises from
      'lipomatous' metaplasia of a pre-existing leiomyoma.

PMID- 8870006
TI  - Clinicopathologic study on clear cell hepatocellular carcinoma.
AB  - In order to study the clinicopathologic characteristics of the clear cell variant
      of hepatocellular carcinoma (HCC), 215 consecutive cases measuring less than 5 cm
      in diameter were reviewed. The cases were divided into clear cell HCC (20 cases);
      focal clear cell HCC (77 cases); and non-clear cell HCC (118 cases). Clinical and
      pathological findings were compared among these groups. Clear cell HCC was
      moderately differentiated in 80% of cases and the incidence was not related to
      tumor size. The male to female ratio was 2.3:1, lower than the 6.9:1 of non-clear
      cell HCC. The association rate with liver cirrhosis was 90%, higher than the
      59.3% of non-clear cell HCC. Three- and five-year survival rates, and no
      recurrence time were 54.5%, 33.3%, and 564 days, respectively, lower than the
      findings of 74.3%, 46.1%, and 770 days for non-clear cell HCC. But there is no
      significant difference in prognosis between both groups. Ultrastructurally, clear
      cells showed abundant glycogen storage and a variable degree of fat vacuoles,
      with a marked reduction of the number and size of organelles in the 8 cases
      examined. Non-clear cells of focal clear cell and non-clear cell HCC showed a
      moderate degree of glycogen storage in 85.7% and 28.6% of the seven cases
      examined from each group, with significant difference. It was concluded that
      clear cell HCC occurs mostly in the moderately differentiated form and is
      characterized by high female prevalence, high rate of association with liver
      cirrhosis, and has no significant difference in prognosis compared with non-clear
      cell HCC.

PMID- 8870007
TI  - Sclerosing peritonitis associated with luteinized thecoma of the ovary.
AB  - A unique case of bilateral luteinized thecomas of the ovary associated with
      sclerosing peritonitis is reported and the clinical and pathological features of
      this and previously reported cases are reviewed. The patient, 52 years of age,
      presented with abdominal distension and diarrhea. Pelvic imaging studies revealed
      bilateral ovarian tumors with ascites. Total abdominal hysterectomy and bilateral
      salpingo-oophorectomy with adhesiotomy of the small bowel were performed.
      Histologically, the ovarian tumor was composed of closely packed spindle to round
      shaped cells, and within the spindle cell population, lutein-like cells were
      scattered singly or in clusters. Mitotic counts of spindle cells revealed 12
      mitotic figures (MF) per 10 high-power fields (HPF) in one part of the left
      ovarian tumor, but other areas of the tumor showed less than 3 MF/10 HPF on
      average. The lesion from the resected small bowel showed prominent fibrosis,
      confined to the serosa with no evidence of metastasis from the ovarian tumor. The
      patient has undergone adhesiotomy with partial resection of the small bowel seven
      times since the first laparotomy because of the recurrent small bowel
      obstruction. The patient has survived with complications due to short bowel
      syndrome for 7 years after the initial surgery and so far no recurrence or
      metastasis of the ovarian tumor has been identified. The case reported here also
      supports the idea that luteinized thecoma of the ovary associated with sclerosing
      peritonitis may be a distinct clinicopathologic entity, in terms of the unique
      association and of the unique features of thecoma; that is, bilateral, hormonally
      inactive and apparently benign in spite of its highly mitotic activity.
      Additional attention should be paid to the patient's quality of life, which is
      often degraded by peritoneal fibrosis and small bowel obstruction.

PMID- 8870008
TI  - Malignant fibrous histiocytoma of the pancreas.
AB  - An extremely rare case of malignant fibrous histiocytoma in the pancreas is
      reported. A 70-year-old man complained of upper abdominal discomfort. A tumor in
      the head of the pancreas was demonstrated by ultrasonography and computed
      tomography. The surgical specimen revealed a relatively well demarcated tumor, 9
      x 7 x 6.5 cm in size. Microscopically, fibroblastic, histiocytic, and
      multinucleated giant tumor cells were observed in the myxoid area, but some tumor
      cells had proliferated in a storiform-pleomorphic pattern. Immunohistochemically,
      some tumor cells were positive for lysozyme, alpha-1-antitrypsin, alpha-1
      antichymotrypsin, and vimentin. Electron microscopically, tumor cells showed a
      combination of fibroblastic and histiocytic features. The patient is currently
      well with no evidence of recurrence or metastasis 22 months after operation.

PMID- 8870009
TI  - Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro
      invasive squamous cell carcinoma and adenocarcinoma in situ.
AB  - A case of small-cell neuroendocrine carcinoma of the uterine cervix associated
      with squamous cell carcinoma and adenocarcinoma in situ is reported. The tumor
      consisted mainly of uniform small cells with a population of intermediate cells
      that resembled carcinoid tumor cells. Foci of micro-invasive squamous cell
      carcinoma and adenocarcinoma in situ were recognized separately, adjacent to the
      main tumor. Both Grimelius stain and immunostaining of serotonin were positive
      for small-cell and intermediate-cell carcinoma. Neurosecretory granules were
      demonstrated by electron microscopy. Microacini with positive mucin staining and
      microvilli-like structures suggested glandular or exocrine differentiation of the
      tumor. Three distinctive types of differentiation, neuroendocrine, exocrine and
      squamous characteristics, were expressed in the tumor.

PMID- 8870010
TI  - Rheumatoid arthritis complicated by pachy- and leptomeningeal rheumatoid nodule
      like granulomas and systemic vasculitis.
AB  - Rheumatoid nodule is a frequent and characteristic extra-articular manifestation
      of rheumatoid arthritis (RA). Its involvement of central nervous system is a rare
      occurrence with only a few reported cases. A 78-year-old man with severe
      arthritis showing the formation of rheumatoid nodule-like granulomas in the dura
      and subarachnoid space along with the spleen is presented. The characteristic
      morphological finding of the granulomas was the presence of neutrophils and the
      absence of definite fibrinoid necrosis, which differed from the typical features
      of rheumatoid nodules previously described. The diagnosis should be based on the
      exclusion of diseases that may cause similar granulomatous reactions including
      infectious diseases. Additionally, there was systemic necrotizing vasculitis in
      the dura and multiple cerebral infarcts, although the association between
      vasculitis and cerebral infarcts was not clear.

PMID- 8870011
TI  - Reticulohistiocytoma involving the skin, subcutaneous tissue and a regional lymph
      node.
AB  - A 30-year-old female complained of a surface-eroded solitary nodule on the right
      thigh. Histologically, the dermal lesion consisted of uniform-sized polygonal
      cells with eosinophilic, 'ground glass' cytoplasm. Mitoses were infrequent. Under
      the histopathologic diagnosis of amelanotic melanoma, wide resection of the skin
      and dissection of the inguinal lymph nodes were performed. The subcutaneous
      tissue and a lymph node showed nodular proliferation of histiocytoid cells, in
      association with hemosiderin-laden multinucleated giant cells. The mononuclear
      cells were immunoreactive for factor XIIIa, while the multinucleated cells were
      positive for CD68, lysozyme and HLA-DR. In the lymph node tissue, a considerable
      number of mononuclear cells positive for CD68 were noted. CD34, alpha-smooth
      muscle actin, desmin and HMB45 were negative. Ultrastructurally, the mononuclear
      cells were rich in 100 nm vesicles and 180-350 nm lysosome-like granules.
      Interdigitation of the plasma membranes was seen in the multinucleated cells. The
      patient did not complain of joint symptoms, and has been disease-free for 5
      years. The histologic and immunohistochemical features are consistent with so
      called 'reticulohistiocytoma', though the site of histiocytic growth was unusual.

PMID- 8870012
TI  - Adenocarcinoma arising within a colonic diverticulum.
AB  - A case of cancer arising in a diverticulum of the ascending colon in a 67-year
      old male is reported. The 1.5 x 1.0 cm well-differentiated adenocarcinoma
      protruded from the base of the inverted mucosa of the diverticulum. The
      surrounding flat colonic mucosa was not involved by the cancerous process. Focal
      stromal invasion was seen in the subserosal tissue, without association of lymph
      nodal involvement. This is the third reported case of adenocarcinoma arising in
      the colonic diverticulum.

PMID- 8870013
TI  - Midline developmental abnormalities of the posterior fossa: correlation of
      classification with outcome.
AB  - Fifty children with developmental retrocerebellar cysts of the posterior fossa,
      treated over an 11-year period, were assessed. The cysts were classified
      according to a morphological classification based on axial computerized
      tomography scans in order to assess the usefulness of this classification with
      regard to treatment and outcome. There were 35 patients with the Dandy-Walker
      complex and 15 patients with posterior fossa cysts. All surgically treated
      patients had cerebrospinal fluid shunting as the only form of treatment.
      Cystoperitoneal shunts were the treatment of choice. Although the morphological
      classification has relevance with regard to the embryological development of the
      cyst, it does not influence the selection of treatment nor the surgical outcome
      following shunt insertion.

PMID- 8870014
TI  - Intracranial ependymomas: analysis of prognostic factors in a population-based
      series.
AB  - A retrospective study of 31 children presenting in the period 1976-1993 with
      intracranial ependymomas in the south-west region of the UK was performed. The
      diagnosis was confirmed by histological review and several histological variables
      recorded, including pleomorphism, cellularity, numbers of mitotic figures and
      extent of necrosis. Histological features, presentation and treatment were
      correlated with outcome. Eleven patients had supratentorial primaries and 20
      infratentorial primaries. Seven patients had macroscopically complete resections
      of which 5 had supratentorial primaries. Eight patients had no other therapy
      apart from surgery. Six patients received craniospinal irradiation, 11 had
      involved-field irradiation and 14 did not have radical radiotherapy. Twelve
      patients received chemotherapy. Eleven patients are relapse-free at a median of
      43 months. Of the 20 relapses, 19 were local and only 1 metastatic. The grade of
      the tumor assigned at presentation had no correlation with outcome. On
      histological review, the only feature that had a significant correlation (p =
      0.05) with survival was tumor cellularity. There was a survival advantage for a
      supratentorial primary site (p = 0.04). The event-free survival was significantly
      longer for patients diagnosed after 1986 than before (p = 0.006). Survival was
      not significantly affected by radiotherapy or chemotherapy. Children who had had
      a macroscopically complete excision of the tumor had a 5-year survival of 69% as
      opposed to 47% for those who had incomplete surgery, but this difference is not
      significant (p = 0.13). The data suggest that: (1) the event-free survival rate
      has improved significantly with time; (2) there is little correlation between a
      variety of pathological features and outcome, and (3) failure at the primary site
      is the major obstacle to improved cure rates. The role of complete resection,
      including second-look surgery, needs further evaluation.

PMID- 8870015
TI  - The role of somatosensory evoked potentials in the evaluation of spinal cord
      retethering.
AB  - Early detection of clinically significant spinal cord retethering is of paramount
      importance for the preservation of neurologic function in patients with repaired
      spinal dysraphic lesions. We retrospectively analyzed 90 children who were
      followed with serial peroneal somatosensory evoked potentials (SEPs) after a
      repair of their spinal dysraphic lesions with the objective of evaluating whether
      SEPs were a useful way of monitoring these children to facilitate early detection
      of clinically significant retethering. Three hundred and nine studies were
      performed on these children yielding a mean of 3.4 studies per patient. The
      median time between SEP studies was 13 months. A clinical examination was
      performed at the time each SEP was done. Sixty-one patients (68%) had a
      myelomeningocele; 25 (28%) had a lipomyelomeningocele while other types of
      dysraphic lesions were found in the remaining 4%. Nineteen patients (21%) had no
      change in serial SEPs; 7 of these 19 (37%) had a deterioration in clinical status
      while the SEPs were stable. Twenty-six patients (29%) showed improvement in
      serial SEPs, however, 3 of the 26 had clinical worsening at the time SEPs
      improved. SEPs deteriorated in 45 patients (50%); 13 of the 45 had an associated
      clinical deterioration, and the remaining 32 were stable clinically. Twenty-three
      patients (26%) had a clinical deterioration; of these only 13 had a corresponding
      deterioration in SEPs, 7 patients had stable SEPs while 3 had improvement in SEPs
      at the time of clinical deterioration. This results in a false-positive rate of
      71% and a false-negative rate of 43%. We conclude that serial SEPs do not
      correlate well with clinical status and are not a useful modality for monitoring
      patients at risk for retethering.

PMID- 8870016
TI  - Prenatal diagnosis and pediatric neurosurgery.
AB  - Advances in realtime ultrasound imaging and a greater availability of high
      quality ultrasound equipment have resulted in an increased number of congenital
      abnormalities being diagnosed prenatally in the last 10-15 years. In addition,
      testing for maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin,
      and serum unconjugated estriol has allowed for more sensitive screening for
      congenital abnormalities. In response to this, in 1989 the Prenatal Diagnosis and
      Treatment Center was established at our institution to coordinate the care of
      fetuses and newborns with congenital malformations and to provide alternatives
      for the parents should the fetus not be carried to term. From January 1990
      through June 1993, our group diagnosed 50 singleton pregnancies with various
      types of central nervous system disorders by the methods outlined above. Thirty
      seven fetuses were diagnosed with neural tube defects. Of these, 5 were
      anencephalic and 1 had an encephalocele. The remaining 31 fetuses had
      meningomyeloceles with associated hydrocephalus. Of these 31, 18 fetuses were
      terminated prior to the age of viability as a result of our counseling and 13
      fetuses were brought to term. Of the remaining 13 fetuses, 8 had hydrocephalus
      and 5 had various other diagnoses. Three of the eight hydrocephalic fetuses were
      either terminated, stillborn, or died following birth. Of the other 5 fetuses
      with hydrocephalus, 3 had shunts placed, 1 was followed with normal head growth,
      and 1 had normal ventricular size at birth. Using the methods available, the
      accuracy of diagnosis is very high, with only 1 fetus in this series being
      incorrectly diagnosed. Additionally the advantages of being able to counsel the
      parents regarding their unborn child allows them to make informed decisions.
      Accurate prenatal diagnosis plays a major role in the care of the fetus and in
      counseling parents prenatally for pediatric neurosurgical problems.

PMID- 8870017
TI  - Seizure outcome in children treated for arteriovenous malformations using gamma
      knife radiosurgery.
AB  - Seizures are the second most common presenting symptom of arteriovenous
      malformations (AVMs) in children. Although radiosurgery has been found to be a
      safe and effective alternative treatment, the outcome of seizure control in
      children after radiosurgery for AVMs is unknown. Between 1987 and 1994, 72
      children under the age of 18 years were treated with gamma knife radiosurgery for
      AVMs at our institution. Fifteen patients (21%) had seizures as part of their
      clinical course. There were 11 boys and 4 girls with ages varying from 2 to 17
      years (median 16 years). Seizures included: generalized tonic-clonic (n = 8);
      focal motor or sensory (n = 4); partial complex (n = 2), and a combination of
      generalized and partial complex (n = 1). Nine lesions were in cortical locations;
      six were subcortical. Spetzler-Martin grades included: II (n = 7); III (n = 4);
      IV (n = 2), and VI (n = 2). During follow-up after radiosurgical treatment, 11 of
      13 patients (85%) were seizure free and off anticonvulsant therapy (mean follow
      up 47 months). Two patients had a significant improvement in their seizures but
      continue on medication. Two of the 72 patients (3%) developed seizures after
      treatment and remain on medication. Seizure outcome was not associated with the
      location or complete obliteration of the lesion. We conclude that stereotactic
      radiosurgery, as a non-invasive alternative, is associated with a good outcome
      for the AVM as well as AVM-related seizures in children.

PMID- 8870018
TI  - Rapid and near-complete resolution of moyamoya vessels in a patient with moyamoya
      disease treated with superficial temporal artery-middle cerebral artery bypass.
AB  - Several groups have reported partial resolution of moyamoya vessels following
      surgical revascularization in pediatric patients, but angiographic documentation
      of near-complete resolution has been poor. We report here a case of a 5-year-old
      boy who underwent bilateral superficial temporal artery-middle cerebral artery
      bypass combined with unilateral encephaloduroarteriosynangiosis who demonstrated
      near-complete resolution of moyamoya vessels and a dramatic improvement in
      cerebral perfusion as measured by xenon-enhanced CT. The resolution of moyamoya
      networks may serve as an indicator of successful surgical revascularization.

PMID- 8870019
TI  - Focal dermal hypoplasia (Goltz syndrome) with vertebral solid aneurysmal bone
      cyst variant. A case report.
AB  - Focal dermal hypoplasia or Goltz syndrome is a rare clinical entity, usually
      presenting in early childhood as a mix of ectodermal and mesodermal anomalies.
      Previously reported cases have included skeletal lesions of the long bones,
      metacarpals, metatarsals and pelvis. We present a case with a vertebral lesion
      causing neurologic deficit. A discussion of the history of the syndrome is
      included as well as detailed histologic description.

PMID- 8870020
TI  - Split cord malformations: report of three unusual cases.
AB  - The unified theory, proposed by Pang et al., explains the embryogenetic
      mechanisms of all variants of split cord malformations (SCMs). All SCMs originate
      from one basic error occurring around the time when the primitive neurenteric
      canal closes. The basic error is the formation of an accessory neurenteric canal
      between the yolk sac and amnion which is subsequently invested with mesenchyme to
      form an endomesenchymal tract that splits the notochord and neural plate. Three
      cases of SCMs which support this unified theory are presented. A 3-month-old girl
      had a combination of both types of SCMs at the level of T11. The 2nd case, a 2
      week-old girl, had type-II SCM associated with a thickened filum terminale,
      lipomyelomeningocele and ectopic renal tissue within lipoma. A lipomatous tract
      extending from a subcutaneous lipoma to the intradural fibrous septum contained
      lymphoid tissues and tubular epithelia in a 3-month-old boy with a type-II SCM.
      These 3 cases support the unified theory.

PMID- 8870021
TI  - Malignant fibrous histiocytoma in a 9-year-old girl.
AB  - A case of malignant fibrous histiocytoma in the left temporoparietal region of a
      9-year-old girl is reported. The tumor was cystic with a mural nodule.
      Microscopically, the tumor focally infiltrated the leptomeninges sparing the dura
      mater, and was composed of glial fibrillary acidic protein-negative cells
      suspended in a rich meshwork of reticulin fibers. Electron microscopy showed the
      presence of extensive thin processes on the cell's surface and lysosomal-like
      inclusions in the cytoplasm. No basal lamina was present around the cells. The
      clinical and pathologic features of this case were compared with those of
      previous cases described in the world literature.

PMID- 8870022
TI  - A review of phosphatidylserine pharmacological and clinical effects. Is
      phosphatidylserine a drug for the ageing brain?

PMID- 8870023
TI  - Acetylcholine release at motor endplates and autonomic neuroeffector junctions: a
      comparison.
AB  - Acetylcholine released at motor endplates and at autonomic neuroeffector
      junctions binds to nicotinic and muscarinic receptors to affect the activity of
      the corresponding target cells. Additionally, nicotonic and muscarinic receptors
      modulate various intracellular regulatory pathways (second messengers, gene
      expression) and mediate trophic effects. To maintain homeostasis of the
      individual cell and of the whole organism the release of acetylcholine has to be
      strictly controlled within both nervous systems. The basic events of synthesis,
      storage, and release are comparable at motoneurones and autonomic neurones, but
      mechanisms regulating transmitter release appear to differ. The motor endplate
      can be regarded as a highly specialized synapse ensuring a focal innervation of
      skeletal muscle fibres. P-type calcium channels are critically involved in
      mediating exocytotic transmitter release. Facilitatory presynaptic receptors
      (nicotinic, muscarinic, alpha 1- and beta 1-adrenoceptors, calcitonin-gene
      related peptide receptors, adenosine A2a receptors) mediate an increase in evoked
      acetylcholine release to allow rapid and maximal activation of skeletal muscles.
      In contrast, neuroeffector junctions innervate the effector cells in a rather
      scattered manner. N-type calcium channels are critically involved in exocytotic
      transmitter release. Inhibitory neuronal receptors (muscarinic, alpha 2- and beta
      adrenoceptors, prostanoid (airways), receptors for NO, P1-purinoceptors) limit
      evoked acetylcholine release to prevent overstimulation of the effector cells.
      These inhibitory mechanisms may also be useful in view of the 100-fold higher
      affinity of acetylcholine at muscarinic receptors than at nicotinic receptors
      (muscular type), a property which may facilitate overstimulation.

PMID- 8870024
TI  - Hypertensive diabetic rats in pharmacological studies.
AB  - Since hypertensive disease and diabetes frequently occur simultaneously there
      exists a requirement for animal models where both pathological entities are
      combined. The streptozotocin (STZ)-spontaneously hypertensive rat (STZ-SHR) and
      the obese Zucker rat are examples of animal models where hypertension and
      diabetes occur simultaneously. STZ-SHRs develop a hyperglycaemic syndrome,
      associated with other biochemical and morphological changes that to some extent
      approach insulin-dependent diabetes mellitus (type 1 diabetes) combined with
      hypertension. The obese (Fa/?) Zucker rat is characterized by the simultaneous
      occurrence of obesity, hyperglycaemia, hyperinsulinaemia, hyperlipidaemia and
      moderate hypertension. As such it approaches the patient with non-insulin
      dependent diabetes mellitus (type 2 diabetes) who is simultaneously hypertensive.
      Lean (fa/fa) Zucker rats are suitable controls with respect to the obese animals.
      Both animal models (STZ-SHRs and obese Zucker rats) were characterized with
      respect to their biochemical, morphometric and haemodynamic properties. Both
      models were examined in particular with respect to the pharmacological
      characteristics of their cardiovascular system, as discussed in the present
      survey.

PMID- 8870025
TI  - The clinical relevance of chronopharmacology in therapeutics.
AB  - Circadian rhythms in the functions of the body are well established, e.g. in
      cardiovascular (blood pressure, heart rate, blood flow, etc.), pulmonary, hepatic
      and renal functions. Also the symptoms and the onset of diseases are not randomly
      distributed within 24 hours of a day (e.g. coronary infarction, angina pectoris
      attacks, silent ischaemia, asthmatic attacks). Accordingly, the effects and/or
      pharmacokinetics of drugs can display significant daily variations. Recent data
      on the chronopharmacodynamics and chronopharmacokinetics of H2-blockers,
      antiasthmatics (theophylline, beta-agonists, glucocorticoids), cardiovascular
      active drugs (beta-blockers, organic nitrates, calcium channel blockers, ACE
      inhibitors) are described as representative examples. The data demonstrate that
      biological rhythms can have an impact on drug therapy.

PMID- 8870026
TI  - Effects of calcium antagonist diltiazem on leukocyte elastase and on reactive
      oxygen species production in human neutrophils.
AB  - During inflammatory disorders, some proteases and very reactive oxygen
      metabolites are produced by activated phagocytic cells. These proteases and
      oxidants are involved in many diseases like tissue injury or atherosclerosis. It
      was shown in vitro that diltiazem, a calcium channel blocker, had antielastase
      and antioxidant properties. This drug inhibited the release of elastase by
      neutrophils in a dose dependent manner when these cells were stimulated by
      phorbol-myristate-acetate (PMA) or by formyl-methionyl-leucylphenylalanine (fMLP)
      with an IC50 of 144.5 microM, and 132.8 microM, respectively. Towards the
      oxidants, the 50% inhibitory concentrations (IC50) of diltiazem are 422 microM,
      138 microM and 165 microM for superoxide anion, hypochlorous acid and hydroxyl
      radical production by PMA stimulated human neutrophils, respectively. In the case
      of fMLP stimulated human neutrophils, the IC50 for superoxide anion is 78 microM.
      When human neutrophils were stimulated by dioctanoylglycerol (DiC8) or by calcium
      ionophore (Ca.I), the IC50 for superoxide anion were 175.5 microM and 186 microM,
      respectively. When human neutrophils were stimulated by opsonized zymosan (OZ),
      diltiazem did not show an inhibition of superoxide production in a dose dependent
      manner. This drug did not act by scavenging elastase or oxidants as demonstrated
      by cell free models. A mechanism of elastase and oxygen metabolites inhibition by
      diltiazem has been considered specially toward the mobilization of cytosolic
      calcium and an inhibition of protein kinase C cannot be excluded. The results
      suggest that diltiazem might contribute to attenuate the development and the
      progression of atheroma where oxidants and elastase have been implicated.

PMID- 8870027
TI  - Intracellular and extracellular Ca2+ regulate histamine-induced release of nitric
      oxide in vascular endothelial cells as shown with sensitive and selective nitric
      oxide electrodes.
AB  - The effects of various agents that alter the intracellular Ca2+ concentration and
      the extracellular Ca2+ concentration on histamine-induced release of nitric
      oxides (NO) from porcine aortic endothelial cells were studied using NO
      electrodes. The NO release induced by application of histamine (200 microM) in
      Ca(2+)-free solution was similar to that in solution with a normal Ca2+
      concentration on its first application, but reduced on its second application. NO
      release was also suppressed by 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'
      tetraacetic acid (BAPTA), which lowers the intracellular Ca2+ concentration, and
      was completely inhibited by Co2+, but it was not affected by verapamil, a voltage
      dependent Ca2+ channel blocker. These results suggest that Ca2+ release from
      intracellular stores might play an important role in NO production, that influx
      of extracellular Ca2+ is required to refill the stores, and that this Ca2+ influx
      is not through voltage-dependent Ca2+ channels.

PMID- 8870028
TI  - Pharmacological activities of Chelidonium majus L. (Papaveraceae).
AB  - Chelidonium majus L. (Papaveraceae) has a long history as being useful for the
      treatment of many diseases in European countries. This plant is of great interest
      for its use also in Chinese herbal medicine. The plant contains, as major
      secondary metabolites, isoquinoline alkaloids, such as sanguinarine, chelidonine,
      chelerythrine, berberine and coptisine. Other compounds structurally unrelated to
      the alkaloids have been isolated from the aerial parts: several flavonoids and
      phenolic acids. C. majus extracts and its purified compounds exhibit interesting
      antiviral, antitumour and antimicrobial properties both in vitro and in vivo.

PMID- 8870029
TI  - Vestibular compensation in aged rats with unilateral labyrinthectomy treated with
      dopaminergic drugs.
AB  - Drugs acting as agonists (SKF38393 and quinpirol) or antagonists (SCH23390 and
      sulpiride) on dopamine receptors were administered at various doses (1, 2 or 4 mg
      kg-1 day-1) to aged male rats of the Sprague-Dawley strain subjected to labyrinth
      unilateral lesion. The time course of vestibular compensation was evaluated by
      recording spontaneous eye nystagmus and by scoring ambulation and rearing with
      the open field test and motor ability and coordination with the rotorod test.
      Treatment started 3 days prior to surgery and continued until day 7 after
      surgery. The vestibular compensation of untreated young male rats was also
      studied with the same methods. The decline of spontaneous nystagmus in aged
      animals was slower than that of young rats and was facilitated by the large doses
      of quinpirol (D2 receptor agonist) and inhibited by sulpiride (D2 receptor
      antagonist) 4 mg kg-1 day-1, while the other drugs did not affect this parameter.
      After operation, ambulation and rearing of aged rats increased more slowly as
      compared to that of young animals. Moreover, motor performance and coordination
      in aged rats improved less rapidly than those of young controls. Dopamine
      receptor agonists increased ambulation and improved motor performance and
      coordination in aged rats, while dopamine receptor antagonists exerted opposite
      effects. Rearing was not affected by any kind of drug treatment. These results
      suggest that dopamine neurotransmission plays a role in vestibular compensation
      process following unilateral labyrinthectomy in aged animals, and this may have
      clinical relevance in vestibular pathologies of peripheral origin that are
      associated to brain ageing.

PMID- 8870030
TI  - Effects of nifedipine and Bay K 8644 on the R-PIA and caffeine-induced changes in
      the locomotor activity of rats.
AB  - Possible interaction between adenosine and L type Ca2+ channel in the locomotor
      activity of rats was investigated. R-PIA (0.05 mg kg-1), an adenosine analogue,
      and caffeine (20 mg kg-1), an adenosine receptor antagonist, significantly
      decreased and increased locomotor activity, respectively. Ca2+ channel blocker
      nifedipine (5 mg kg-1) and the channel activator Bay K 8644 (0.5 mg kg-1) did not
      alter the locomotor activity. However, both drugs significantly potentiated the
      inhibitory effect of R-PIA on the locomotor activity. Additionally, caffeine
      induced increase in the locomotor activity was significantly blocked by
      nifedipine and Bay K 8644. This interaction might be due to the inhibitory
      effects of nifedipine and Bay K 8644 on the uptake of adenosine by rat brain.

PMID- 8870031
TI  - The mechanism by which the selective 5-HT1A receptor antagonist S-(-) UH 301
      produces head-twitches in mice.
AB  - Electrophysiological studies indicate that certain 5-HT1A receptor antagonists
      increase the basal firing rate of some but not all raphe neurons by antagonizing
      the inhibitory endogenous serotonin tone operating on the somatodendritic pulse
      modulating presynaptic 5-HT1A autoreceptors. This effect should enhance the
      synaptic concentration of 5-HT (5-hydroxytryptamine) in serotonergic terminal
      fields, which may then activate postsynaptic 5-HT receptors. However, in vivo
      microdialysis studies show that generally such 5-HT1A antagonists by themselves
      do not increase the basal 5-HT release but potentiate the ability of serotonin
      reuptake blockers to increase the neuronal serotonin terminal output in the rat
      brain via the above mechanism. The purpose of the present study was to determine
      whether antagonism of the proposed endogenous serotonin tone on the 5-HT1A
      autoreceptors can potentiate the activity of other postsynaptic serotonin
      receptors. To this end, we utilized the head-twitch response (HTR) in mice as an
      in vivo model of postsynaptic 5-HT2A receptor function. The selective and silent
      5-HT1A receptor antagonist, S-(-)UH 301, by itself, in a dose-dependent manner,
      produced the HTR in normal but not in reserpinized animals. The 5-HT2A
      antagonist, SR 46349B, completely prevented S-(-)UH 301-induced HTR. Pretreatment
      with S-(-)UH 301 also potentiated 5-hydroxytryptophan (5-HTP)-induced HTR both in
      normal and in the reserpinized mice. At low doses (0.06-0.25 mg/kg), the 5-HT2A
      selective agonist, 8-OH DPAT, significantly but partially inhibited 5-HTP-induced
      HTR. However, further attenuation was not observed following the administration
      of larger doses of 8-OH DPAT. Depending upon the dose used, S-(-)UH 301
      pretreatment not only antagonized but also broke through the inhibitory effect of
      8-OH DPAT on 5-HTP-induced HTR. The selective (sertraline) and nonselective
      (cocaine) serotonin reuptake blockers potentiated the ability of 5-HTP to induce
      the head-twitch behavior in mice. Pretreatment with S-(-)UH 301 enhanced the
      potentiating effect of serotonin reuptake blockers on the 5-HTP induced HTR.
      These results suggest that an endogenous 5-HT tone via the discussed mechanism
      controls the terminal field synapticactivity of serotonergic neurons in mice. In
      addition, disinhibition of pulse-modulating 5-HT1A autoreceptors by S-(-)UH 301
      can potentiate the synaptic effects of serotonin reuptake blockers as well as the
      serotonin precursor 5-HTP. However, a more firm general conclusion regarding
      antagonism of presynaptic 5-HT1A receptors leading to indirect functional
      enhancement of other postsynaptic serotonergic receptors can only be made when
      the above hypothesis is further tested with other selective 5-HT1A receptor
      antagonists (such as WAY 100 635), which we were unable to obtain. The present
      study is the first report to show that a selective 5-HT1A antagonist by itself
      can produce a serotonin-mediated function via indirect stimulation of another
      serotonin receptor subtype in mice.

PMID- 8870032
TI  - Inhibition by MK-801 of morphine-induced conditioned place preference and
      postsynaptic dopamine receptor supersensitivity in mice.
AB  - Intraperitoncel injection of morphine (5 mg/kg) in mice every other day for 8
      days produced conditioned place preference (CPP). CPP effects were evaluated by
      assessing the difference in time spent in the drug-paired compartment and the
      saline-paired compartment of the place conditioning apparatus. The injection of a
      noncompetitive NMDA antagonist, MK-801 (0.05 and 0.1 mg/kg. IP), prior to and
      during morphine treatment in mice inhibited morphine-induced CPP. The development
      of postsynaptic dopamine (DA) receptor supersensitivity in mice displaying a
      morphine-induced CPP was evidenced by the enhanced response in ambulatory
      activity to the DA agonist, apomorphine (2 mg/kg). MK-801 inhibited that
      development of postsynaptic DA receptor supersensitivity. MK-801 also inhibited
      apomorphine-induced climbing behavior, suggesting that MK-801 inhibits
      dopaminergic activation mediated via the NMDA receptor. These results suggest
      that the development of morphine-induced CPP may be associated with the
      development of postsynaptic DA receptor supersensitivity. The development of
      morphine-induced CPP and DA receptor supersensitivity may be closely related to
      NMDA receptor-mediated dopaminergic activity, because morphine-induced changes in
      sensitivity to apomorphine, as well as apomorphine-induced climbing behavior in
      morphine treated mice, were both blocked by MK-801.

PMID- 8870033
TI  - Stimulatory vs. inhibitory effects of acute stress on plasma LH: differential
      effects of pretreatment with dexamethasone or the steroid receptor antagonist, RU
      486.
AB  - Acute stress elicits variable patterns of pituitary LH release in intact rats.
      While the pituitary-adrenal axis is capable of discrimination between stressors
      of graded intensity, the effects of variable glucocorticoid output on the
      direction and magnitude of LH release during stress remain unclear. The present
      studies compared the effects of a psychological stress and two different physical
      stressors on peripheral corticosterone (CORT) and LH concentrations. Plasma CORT
      levels were elevated during each stress, but this increase in hormone release was
      significantly greater in response to physical stress. This differential CORT
      sensitivity to psychological vs. physical stress was correlated with divergent
      patterns of pituitary LH release; novel environment (NE) stress resulted in a
      transient increase in plasma LH, whereas both physical stressors ultimately
      caused a reduction in circulating hormone levels. Pretreatment with the
      glucocorticoid receptor (GR) antagonist, RU 486, reversed physical stress-induced
      decreases in LH release, but did not further facilitate circulating LH during NE
      stress. Other studies showed that stimulation of GRs prior to stress with the
      potent ligand, dexamethasone (DEX), blunted the stimulatory effects of NE stress
      on circulating LH. Additional experiments investigated whether prolonged exposure
      to elevated glucocorticoid levels elicits adaptive responses from the
      hypothalamic-pituitary LH axis to acute stress. Chronic DEX administration
      resulted in a significant attenuation of the inhibitory LH response to acute
      immobilization, but had no impact upon the facilatory effects of NE stress on LH
      release. The current studies confirm previous reports of variation in the
      magnitude of CORT secretion elicited by stressors of different intensity, and
      provide new evidence that inhibitory patterns of pituitary LH release may be
      correlated with a high degree of activation of the pituitary-adrenal axis.
      Attenuation of the facilatory effects of novel environment stress on LH release
      by pretreatment with the GR agonist, DEX, suggests that GR-induced inhibition of
      LH requires occupation of GRs beyond that which occurs during this mild stressor.
      The present findings that stress-induced decreases in plasma LH are blunted by
      chronic glucocorticoid exposure support a role for glucocorticoid-dependent
      mechanisms in adaptation of GR-mediated inhibitory responses to stress.

PMID- 8870034
TI  - Conditioned increase in peripheral blood mononuclear cell (PBMC) number and
      corticosterone secretion in the rat.
AB  - Femoral artery catheters were surgically implanted into male Lewis/N rats to
      allow blood sampling and drug infusion in the freely moving animal. After
      recovery, conditioned animals received four pairings of a peppermint odor, the
      conditioned stimulus (CS), and an infusion of 0.1 mg/kg nicotine bitartrate, an
      unconditioned stimulus (US) for an increase in the number of peripheral blood
      mononuclear cells (PBMC) and an increase in corticosterone concentration. When
      reexposed to the peppermint odor, conditioned animals showed a significant
      increase in PBMC number and corticosterone secretion when compared to saline and
      unpaired control groups and previously conditioned animals that were not
      reexposed to the CS. Increased PBMCs were found on the fifth unreinforced CS
      trial. Conditioned CORT responses were lost after the initial test trial. The
      data indicate that the distribution of immune cells can be influenced by learning
      processes and support the role of learning in the regulation of corticosterone
      secretion.

PMID- 8870035
TI  - 5-HT3 receptor antagonists do not modify cocaine place conditioning or the rise
      in extracellular dopamine in the nucleus accumbens of rats.
AB  - Three 5-HT3 receptor antagonists, MDL 72222, tropisetron, and ondansetron were
      studied for their ability to modify the conditioned place preference (CPP)
      induced by 10 mg/kg IP cocaine in rats. MDL 72222 (0.03-3 mg/kg SC) and
      tropisetron (0.01-0.1 mg/kg SC) administered, respectively, 30 min and 1 h before
      each conditioning session, did not affect the acquisition of cocaine CPP.
      Ondansetron (0.01-0.1 mg/kg SC) administered 30 min before each conditioning
      session or just before testing likewise had no effect. At 0.1 mg/kg SC
      ondansetron did not modify the increase of extracellular dopamine caused by 10
      mg/kg cocaine in the nucleus accumbens. The results suggest that 5-HT3 receptor
      antagonists have no effect on the rewarding properties of cocaine or on the
      behaviour elicited by the stimuli previously associated with the drug's action.

PMID- 8870036
TI  - Tolerance to anticonvulsant effects of some benzodiazepines in genetically
      epilepsy prone rats.
AB  - The development of tolerance to the anticonvulsant effects of clonazepam,
      clobazam, and diazepam were studied in genetically epilepsy-prone rats following
      intraperitoneal (IP) or oral administration. The anticonvulsant effects were
      evaluated on seizures evoked by means of auditory stimulation (109 dB, 12-16
      kHz). All compounds showed 60 min after IP injection antiseizure activity with
      ED50 against clonus of 0.24 mumol kg-1 for clonazepam, 0.72 mumol kg-1 for
      diazepam, and 3.9 mumol kg-1 for clobazam. After 120 min of oral administration
      the ED50 against clonus of 2.37 mumol kg-1 for clonazepam, 15.8 mumol kg-1 for
      diazepam, and 30 mumol kg-1 for clobazam. The dose chosen for the chronic
      treatment were 2.5 mumol kg-1 for clonazepam, 15 mumol kg-1 for diazepam, and 30
      mumol kg-1 for clobazam. The animals were treated three times daily for 4 or 6
      weeks. Auditory stimulation was administered 60 min after drug IP injection on
      various days. During treatment, tolerance was observed as a loss of drug
      anticonvulsant effects. No changes of occurrence of audiogenic seizures was
      observed in rats treated with vehicle. Tolerance to the anticonvulsant activity
      developed most rapidly during clobazam treatment, less rapidly following diazepam
      treatment, and most slowly during clonazepam treatment. Sixty minutes after IP
      injection on various days of chronic treatment the motor impairment induced by
      these benzodiazepines was also studied by means of a rotarod apparatus. The
      tolerance to the motor impairment developed more rapidly than the anticonvulsant
      effects. The response to auditory stimulation to benzodiazepines was stopped 24
      and 48 h after chronic treatment with these compounds, showing no residual drug
      effects and that rats were still tolerant. The genetically epilepsy-prone rats is
      a reliable and sensitive model for studying long-term effects of anticonvulsant
      drugs.

PMID- 8870037
TI  - The role of histaminergic-noradrenergic axis in naloxone-induced withdrawal
      symptoms in mice.
AB  - The effects of histamine antagonists on naloxone-precipitated withdrawal symptoms
      were studied in morphine-dependent mice. Chlorpheniramine (0.5-10 mg/kg), a H1
      blocker, given 1P 30 min before naloxone challenge produced a dose-dependent
      potentiation of withdrawal body weight loss, burrowing, and hypothermia, but did
      not influence either jumping or wet-dog shakes. On the other hand, cimetidine (10
      100 mg/kg), a H2-blocker, produced dose-dependent potentiation of withdrawal
      hypothermia and jumping. Cimetidine was without effect on wet-dog shakes,
      burrowing, and body weight loss. The effect of chlorpheniramine was investigated
      in mice injected with 6-hydroxydopamine (6-OHDA) intracerebrally to examine
      whether histamine-mediated effects are some-how linked to noradrenergic pathways.
      Intracerebral injection of 6-OHDA in 5-day-old mice pups resulted in
      hyperlocomotion by the end of 30 days before initiation of morphine dependence.
      Mice pretreated with 6-OHDA developed a higher degree of naloxone-induced
      withdrawal jumping than nontreated mice. 6-OHDA (50 micrograms) lesions
      completely blocked the potentiating effect of chlorpheniramine on burrowing,
      hypothermia, and even reversed the effect on body weight loss. These findings
      suggest that both histamine H1- and H2-receptors may be involved in the
      expression of precipitated withdrawal in morphine-dependent mice and histamine
      receptors function as modulators of noradrenergic neurotransmission.

PMID- 8870038
TI  - The new muscarinic M1-receptor agonist YM796 evokes yawning and increases
      oxytocin secretion from the posterior pituitary gland in rats.
AB  - The present experiments were performed to examine the effects of a new muscarinic
      M1-receptor agonist, (-)-YM796 ((-)-S-2,8-dimethyl-3-methylene-1-oxa-8
      azaspiro[4.5]decane L-tartrate monohydrate), on yawning and oxytocin secretion
      from the posterior pituitary gland in rats YM796, at doses of 2.5-50 mg/kg (SC),
      elicited yawning. The yawning response was markedly increased by pretreatment
      with a beta-adrenoceptor antagonist, pindolol (20 mg/kg, IP), which per se did
      not elicit yawning. The yawning induced by YM796 (10 mg/kg, SC) in combination
      with pindolol (20 mg/kg, IP) was inhibited by scopolamine (0.5 mg/kg, SC), a
      muscarinic receptor antagonist, and pirenzcpine (300 micrograms/ rat, ICV) and
      EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) (5 mg/kg, IP), muscarinic
      M1-receptor antagonists, but not by spiperone (0.5 mg/kg, SC), a dopamine D2
      receptor antagonist, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide)
      (100 micrograms/rat, ICV), a muscarinic M3-receptor antagonist, and [d(CH2)5,
      Tyr(Mc)2, Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist.
      YM796 at 2.5-50 mg/kg (SC) did not exert an action on prolactin levels but
      increased oxytocin secretion from the posterior pituitary gland in rats. This
      augmentation of oxytocin secretion by YM796 was inhibited by scopolamine (0.5
      mg/kg, SC) and pirenzepine (3 mg/kg, SC), but not by mecamylamine (1 mg/kg, IP),
      a nicotinic receptor antagonist. The present findings obtained with YM796 suggest
      that the muscarinic M2-receptor stimulation participates in causing yawning
      behavior and oxytocin secretion in rats.

PMID- 8870039
TI  - Combined pCPA and muscarinic antagonist treatment produces a deficit in rat water
      maze acquisition.
AB  - A 3-day treatment with p-chlorophenylalanine (pCPA, 100 mg/kg/day) produced a
      significant decrease (63-89%) in 5-HT levels in both the hippocampus and the
      cortex of rats, while noradrenaline, adrenaline, and dopamine levels were
      unaffected. Treatment with pCPA alone did not affect the acquisition of a spatial
      learning task in the water maze. Treatment with low doses of either scopolamine
      (0.25 mg/kg) or atropine (10 mg/kg) was also insufficient to cause a significant
      impairment of water maze acquisition. However, a combined treatment of a 3-day
      pCPA regimen with the low dose of atropine or scopolamine produced a significant
      deficit in the acquisition of a water maze task.

PMID- 8870040
TI  - Comparison of the behavioural effects of infusion of carbachol and
      acetylcholinesterase into the rat substantia nigra.
AB  - It has been postulated for many years that acetylcholinesterase (AChE) may play a
      nonclassical role in the substantia nigra, unrelated to its ability to hydrolyse
      acetylcholine. In this study the behavioural effects of unilateral infusion of
      AChE and a cholinergic agonist, carbachol, were compared. Carbachol induced
      ipsiversive circling over a very short time scale (minutes), whereas AChE induced
      contraversive circling, but over a longer time course-10 days. Both agents showed
      selectivity of response within the substantia nigra: acetylcholinesterase was
      only effective when infused into the most rostral region of the substantia nigra
      and its effects were limited to the pars compacta. In contrast, carbachol had
      effects in both the pars compacta and reticulata, with a graded sensitivity to
      carbachol in the rostral/caudal plane; infusions into rostral regions induced
      high rates of circling compared to more caudal areas, suggesting that the
      cholinergic input to the substantia nigra is not homogenous, but greater in
      rostral regions. This disparity between the effects of carbachol and AChE would,
      therefore, suggest that AChE is not exerting its long-term behavioural actions
      via a cholinergic mechanism, both in terms of time course of the response and the
      areas within the substantia nigra sensitive to these agents.

PMID- 8870041
TI  - Increased food intake following injection of the benzodiazepine receptor agonist
      midazolam into the IVth ventricle.
AB  - Despite a prolonged period of research with benzodiazepines, the central site(s)
      of action for the hyperphagic effects of these compounds remains to be
      determined. The aim of the present studies was to examine the effect of direct
      administration of the benzodiazepine receptor agonist midazolam into the IVth
      ventricle on ingestive behavior in nondeprived rats. In Experiment 1,
      microinjection of midazolam (3 and 30 micrograms/microliter) into the IVth
      ventricle was sufficient to increase consumption of a palatable mash. In
      Experiment 2, the hyperphagic effect was blocked by systemic administration of
      the selective benzodiazepine receptor antagonist flumazenil (20 mg/kg). The
      results indicate that a brainstem site of action may be important for the effects
      of benzodiazepine receptor agonists on ingestive behavior.

PMID- 8870042
TI  - Low-dose apomorphine attenuates morphine-induced enhancement of brain stimulation
      reward.
AB  - Thresholds for brain stimulation reward (BSR) delivered to the medial forebrain
      bundle-lateral hypothalamus were determined by means of a rate free
      psychophysical method. Lower doses of apomorphine (0.5 to 0.2 mg/kg) produced
      modest elevations in BSR thresholds. A 0.4 mg/kg dose of apomorphine resulted in
      emergence of stereotypic behaviors and the loss of stimulus control. Morphine's
      BSR threshold lowering effects were significantly blocked by the concurrent
      administration of a 0.1 mg/kg dose of apomorphine. These results support the
      hypothesis that presynaptic dopamine neurons are involved in the mediation of
      morphine's reinforcing effects and that dopamine autoreceptor agonists may be of
      some use in the pharmacotherapy of opiate abuse.

PMID- 8870043
TI  - Behavioral and analgesic effects induced by administration of nifedipine and
      nimodipine.
AB  - Evidence exists that calcium antagonists can have effects on neural function. The
      aim of this work is to analyze the effect of two dihydropyridines, nifedipine and
      nimodipine, administered for 11 days on the behavior and pain sensitivity of
      rats. Nociception was tested using the tail electric stimulation test, and
      behavior parameters using a holeboard. Our results show that chronic
      administration of nifedipine or nimodipine induces analgesia that can be
      evaluated by tail withdrawal. However, neither the vocalization nor the
      vocalization after discharge were modified, so the analgesia may be mediated by
      spinal mechanisms. Rats treated with nifedipine or nimodipine exhibited a dose
      dependent tendency to avoid the center of the field without modification of other
      parameters, suggesting an increased emotivity in the rats. This conclusion is
      supported by the fact that anxiogenic or anxiolytic drugs modify the pattern of
      locomotion without significant changes in other parameters related with the
      motility. The results from this study suggest the view of a complex mechanism of
      action underlying nifedipine- and nimodipine-mediated behavioral effects.

PMID- 8870044
TI  - Side effects of physostigmine as a pretreatment in guinea pigs.
AB  - To prevent incapacitation following nerve agent intoxications, it is proposed to
      replace pyridostigmine by the centrally active carbamate physostigmine (PHY).
      Behavioral and neurophysiological effects of PHY were determined and whether
      these effects would be counteracted by scopolamine. In addition, we compared them
      with the effects of another reversible cholinesterase (ChE) inhibitor ethyl-p
      nitrophenylphosphoramidate (PNF) At similar levels of blood AChE inhibition, PHY
      caused a larger shuttlebox performance decrement than PNF, which was antagonized
      by scopolamine (0.1 mg/kg). SCO enhanced the PHY-induced increase of the auditory
      startle response, whereas PNF, with or without scopolamine, had no effect. In the
      EEG, PHY led to a power increase at the theta 2-alpha 1 band, also found after
      PNF, and at the theta 1 band. SCO antagonized all EEG effects, but not the
      effects of PHY on visual evoked responses, in contrast to those of PNF. Based on
      the different effects of both inhibitors, it is suggested that at relevant doses
      several PHY-induced phenomena occur that are unrelated to AChE inhibition.

PMID- 8870045
TI  - Effects of St-587 and prazosin on water maze and passive avoidance performance of
      scopolamine-treated rats.
AB  - The present experiments were designed to investigate whether the alpha-1
      adrenergic and muscarinic cholinergic systems interact in the regulation of
      spatial navigation behavior in the Morris water maze test and passive avoidance
      performance. Pretraining administration of scopolamine, a muscarinic antagonist,
      markedly impaired the acquisition of water maze task (a hidden platform version)
      as well as retention of this task. The drug also impaired slightly navigation to
      a visible platform. Pretraining subcutaneous administration of St-587 (alpha-1
      agonist) at 2000 micrograms/kg slightly improved the water maze navigation to a
      hidden platform in control rats, but its effect was not augmented in scopolamine
      treated rats. Pretraining administration of prazosin (alpha-1 antagonist) 1000
      micrograms/kg or 2000 micrograms/kg did not significantly potentiate the
      scopolamine (muscarinic cholinergic antagonist)-induced (doses 200 micrograms/kg
      and 100 micrograms/kg, pretraining intraperitoneal injection) deficit in water
      maze navigation. Pretraining administration of prazosin at doses 1000
      micrograms/kg and 2000 micrograms/kg or St-587 at doses 1000 micrograms/kg and
      2000 micrograms/kg did not have any significant influence on scopolamine-induced
      (200 micrograms/kg or 400 micrograms/kg) disruption in passive avoidance
      performance. These findings suggest that alpha-1 adrenergic mechanisms do not
      participate or are not the most important component of the noradrenergic system
      in the interaction between noradrenaline and muscarinic receptors in the
      modulation of learning and memory. The analysis of results indicates that
      activation of alpha-1 adrenoceptors might facilitate the acquisition of water
      maze task in its initial phase, for instance, switching from wall hugging
      strategy to an active exploration strategy. Furthermore, the present data suggest
      that muscarinic cholinergic blockade may affect both mnemonic and nonmnemonic
      processes in rats.

PMID- 8870047
TI  - Disruption of tolerance to the ataxic effect of ethanol by an extraneous
      stimulus.
AB  - According to a conditioning analysis, pharmacological conditional responses (CRs)
      contribute to tolerance. We previously reported that, as expected on the basis of
      this model, tolerance to the hypothermic effect of ethanol is attenuated by
      "external inhibition," for instance, by presentation of a novel stimulus (a
      strobe). However, results of more recent research indicate that novel stimuli
      augment the hypothermic effect of ethanol in rats receiving the drug for the
      first time. It is possible, therefore, that a novel stimulus apparently
      attenuates ethanol tolerance because it augments ethanol-hypothermia, rather than
      because it functions as an external inhibitor. Two experiments were designed to
      evaluate external inhibition of tolerance to another effect of ethanol-ataxia.
      Although the initial ataxic effect of the drug (unlike the hypothermic effect) is
      not enhanced by a novel stimulus, the stimulus reinstated ethanol-induced ataxia
      in tolerant rats. The results demonstrate external inhibition of ethanol
      tolerance in a preparation not confounded by the effects of the novel stimulus on
      initial responding to ethanol.

PMID- 8870046
TI  - Dose- and conditioning trial-dependent ethanol-induced conditioned place
      preference in Swiss-Webster mice.
AB  - The motivational effects of ethanol were examined in Swiss-Webster mice using an
      unbiased place conditioning, design. Adult male Swiss-Webster mice received six 5
      min pairings of a tactile stimulus with different doses of ethanol (1, 2, 3, or 4
      g/kg. IP). A different tactile stimulus was paired with saline injections. A 60
      min preference test was given after the first four conditioning trials and an
      additional 30-min preference test after the sixth conditioning trial. During
      conditioning, ethanol initially produced locomotor stimulation at the 2 g/kg dose
      and locomotor depression at the 4 g/kg dose. However, after repeated ethanol
      exposure, all doses produced overall increases in activity relative to saline,
      suggesting sensitization to ethanol's stimulant effect. After four conditioning
      trials ethanol-induced conditioned place preference was noted in mice receiving 3
      and 4 g/kg ethanol. After two additional conditioning trials all ethanol doses
      produced conditioned place preference. These results indicate that ethanol has
      dose-dependent rewarding effects measured in an unbiased place-conditioning
      paradigm using a standard outbred mouse strain. Further, additional place
      conditioning trials enhance the development of preference at lower (1 or 2 g/kg)
      ethanol doses.

PMID- 8870048
TI  - Delayed arousal from anesthesia: a further similarity between stress and beta-1
      adrenoceptor blockade.
AB  - The present studies investigated the role of beta adrenergic receptors in
      mediating arousal from anesthesia and the effects of stress on this process. In
      support of previous findings by others, it was found that blockade of beta-1 and
      beta-2 receptors by propranolol delayed arousal from halothane anesthesia and
      that this effect was attributable to blockade of beta-1 receptors because it was
      duplicated by betaxolol but not by ICI 118,551. Restraint stress also produced a
      delay in arousal from both halothane and hexobarbital anesthesia. This effect,
      which was observed at 0.5 but not 24 h after the stress, could not be explained
      by a stress-induced alteration in the metabolism of the anesthetic, as no
      difference in brain concentration of hexobarbital was found between stressed and
      control mice. The parallel effects of beta-1 blockade and stress further supports
      the hypothesis that stress produces an impairment in function at either the beta
      1 receptor or some process coupled to this receptor.

PMID- 8870049
TI  - Pharmacological characterization of the enhancement of apomorphine-induced
      gnawing in mice by cocaine.
AB  - The present study was designed to provide additional information on the
      behavioral and pharmacological mechanisms associated with the augmentation of
      apomorphine-induced gnawing in C57BL/6J mice. (-)-Cocaine enhanced apomorphine
      induced gnawing at doses devoid of effects on gnawing when given alone. The
      effect was stereoselective, with (+)-cocaine devoid of activity in this test.
      Peripheral synapses may also not be critical to the cocaine enhancement, as
      cocaine methiodide, a charged species, was also without effect. The local
      anesthetic actions of cocaine were evaluated with lidocaine, a local anesthetic
      without prominent dopaminergic actions. Like (-)-cocaine, lidocaine augmented the
      gnawing response to apomorphine without increasing climbing or gnawing when given
      alone. (+)-Amphetamine enhanced apomorphine-induced gnawing but only at a high
      dose that increased gnawing by itself. The selective dopamine uptake blocker. GBR
      12909, augmented apomorphine-induced gnawing without increasing gnawing when
      given alone; however, unlike cocaine or lidocaine, GBR 12909 increased climbing
      at doses that augmented the gnawing response. These data indicate that the
      cocaine-augmented gnawing response to apomorphine does not appear to be the
      result of psychomotor stimulation per se. Rather, this effect may be due to
      blockade of dopamine uptake and/or the local anesthetic actions of cocaine.

PMID- 8870050
TI  - Changes in behavior and monoamine levels in microdialysate from dorsal striatum
      after 6-OHDA infusions into ventral striatum.
AB  - Long-Evans rats received bilateral 6-hydroxydopamine infusions into the nucleus
      accumbens and were tested immediately (1 and 2 days) or after a recovery period
      (14 and 15 days) for changes in extracellular levels of dorsal striatal
      monoamines using in vivo microdialysis. Compared to controls, the monoamine
      metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5
      hydroxyindoleacetic acid were generally enhanced when tested immediately after 6
      hydroxydopamine treatment, including spontaneous levels and those following
      depolarizing infusions of potassium (60 mM, 20 min) through the microdialysis
      probes. Following 2 weeks recovery, dopamine metabolite levels were depressed and
      the serotonin metabolite levels remained enhanced. D-Amphetamine sulfate (1.5
      mg/kg, SC) stimulated dopamine overflow was enhanced 2 days after 6
      hydroxydopamine administration, but not after 2 weeks recovery. In contrast,
      potassium increased dopamine overflow to the same extent as control animals
      regardless of recovery period following 6-hydroxydopamine. The immediate changes
      in striatal monoamine activity were accompanied by a potentiation of amphetamine
      induced stereotyped behaviors. We suggest that transient presynaptic changes
      within the dorsal striatum following disruption of the ventral striatum may
      mediate some general aspects of loss and recovery of behavior related to the time
      course of 6-hydroxydopamine neurotoxicity.

PMID- 8870051
TI  - Antinociceptive effects of repeated systemic injections of calcitonin in formalin
      induced hyperalgesic rats.
AB  - Calcitonin (CT) produces long-lasting analgesia in patients suffering from
      painful diseases following repeated systemic injections, but there have been only
      a few contradictory reports on the antinociceptive action of systemic injections
      of CTs in animal experiments. This study was conducted to elucidate an
      antinociceptive action of systemic CT in rats. An injection of dilute formalin
      induced hyperalgesia for about 2 h. Single topical injections of 0.12 and 1.2 U,
      but not 0.012 U, of [Asu1.7] eel CT (eCT) into the same site of formalin
      injection inhibited the hyperalgesia. Repeated systemic injections of eCT (4 and
      40, but not 0.4, U kg-1 day-1) for 7 days inhibited the hyperalgesia, while the
      single injection was without effects at doses tested. Although the highest dose
      of eCT (40 U kg-1 day-1) inhibited an increase in body weight following repeated
      injections, lower doses (0.4 and 4 U kg-1 day-1) were without effects. The
      suppression of hyperalgesia following repeated systemic injections of eCT (4 U kg
      1 day-1) lasted for at least 24 h, and subsided by 3 days following the last eCT
      injection. These results indicate that the repeated systemic injections of eCT
      produce a long-lasting inhibition of formalin-induced hyperalgesia in rats. This
      inhibitory effect is similar to CT analgesia in human subjects in terms of a
      necessity for repeated administration, effective dose and long-lasting effects.

PMID- 8870052
TI  - Effects of neonatally administered iprindole on adult behaviors of rats.
AB  - In past studies, administration of the antidepressant drugs clorimipramine,
      zimeldine, or desipramine to neonatal rats produced abnormalities in adult rats
      that modeled some behavioral and/or REM sleep features of human endogenous
      depression. Although these three drugs affected different neurotransmitter
      systems, all caused REM sleep deprivation (RSD). This suggested the hypothesis
      that RSD of neonatal rats caused their adult depression. One prediction of this
      hypothesis is that neonatally administered iprindole, an antidepressant drug that
      does not produce RSD, will not produce adult rats that model depression. The
      present study tested this hypothesis. Iprindole was administered to neonatal
      experimental rats and saline was administered to neonatal control rats. When the
      rats matured, compared with control rats, experimental rats were not
      significantly different in aggressive behavior (shock induced fighting), sexual
      behaviors, open field locomotion, and REM sleep. In our previous studies on rats,
      all these adult behaviors were affected in a depressive-like way by neonatally
      administered clorimipramine. Because iprindole does not decrease REM sleep, the
      present results support the hypothesis that in rats neonatal RSD causes adult
      depression.

PMID- 8870053
TI  - Discriminative stimulus effects of the NMDA receptor antagonists MK-801 and CGP
      37849 in rats.
AB  - Rats were trained to discriminate MK-801 (0.05 mg/kg, IP), an uncompetitive, or
      CGP 37849 (3 mg/kg, IP), a competitive NMDA receptor antagonist from saline,
      using a two-lever, operant drug discrimination paradigm. In generalization tests
      the role of dopaminergic and serotonergic systems in the discriminative stimulus
      effects produced by both NMDA receptor antagonists was studied with amphetamine
      (0.5 mg/kg), cocaine (5.0 and 7.5 mg/kg), and fenfluramine (2.5 and 5.0 mg/kg).
      Additionally, memantine (5.0, 7.5 and 10.0 mg/kg), an uncompetitive NMDA receptor
      antagonist, was tested. The discriminative stimuli produced by MK-801 and CGP
      37849 were not generalized to each other. Among the tested drugs only memantine
      generalized to the MK-801 discriminative stimulus. None of the tested drugs
      showed CGP 37849-like discriminative stimulus properties. The different
      mechanisms underlying NMDA antagonism by MK-801 and GP 37849 might explain the
      observed lack of cross-generalization. The results suggest that dopaminergic and
      serotonergic systems are not of major importance in the discriminative stimulus
      effects produced by both MK-801 and CGP 37849.

PMID- 8870054
TI  - Differential sexual activity of isolated and group-housed male mice: lack of
      substantial influence of acute or chronic naloxone administration.
AB  - Influences of naloxone upon male sexual behavior were examined using two
      different baseline activity levels: individually and group-housed mice. In
      Experiment 1, single injections of 0,12.5, or 50 micrograms per animal were
      administered before testing. Isolated mice showed more sexual activity than did
      grouped mice; naloxone failed to alter those differences. In Experiment 2, a
      similar result was obtained despite administration of 50 or 150 micrograms per
      animal of naloxone. In Experiment 3,0 or 50 micrograms of naloxone was
      administered to isolated or grouped males daily on the 5 days before testing.
      Isolated mice showed performance superior to that of grouped mice, but there was
      no effect of the drug. In Experiment 4, doses of 0. 12.5, or 50 micrograms of
      naloxone were given to isolated or grouped males twice daily for 7 days prior to
      testing, producing little effect. These results suggest that the influences of
      prior social condition on male sexual activity are robust in the face of naloxone
      administration.

PMID- 8870055
TI  - X-ray microtomography of bones and teeth.
AB  - X-ray microtomography is a miniaturized version of computerized axial tomography
      with a resolution of the order of micrometres. In the biomedical field it is
      particularly useful in the study of hard tissue because of its ability to
      accurately measure the linear attenuation coefficient. From this, the mineral
      concentration can be computed, which is one measure of bone quality. Using
      microtomography it is also possible to form three-dimensional images of bone from
      which structural parameters can be derived which could not be measured using
      conventional histomorphometry. Various types of microtomography scanner have been
      used, including simple translate-rotate systems which are capable of measuring x
      ray attenuation at multiple energies simultaneously, and "cone-beam' systems
      which can acquire the necessary data for three-dimensional reconstructions in a
      relatively short time. Both laboratory x-ray sources and synchrotrons have been
      used in the study of hard tissue using microtomography. Most studies of bone have
      been concerned primarily with either the mineral concentration in cortical bone
      or the structure in cancellous bone. The mineral concentration in teeth has also
      been studied, in particular the loss of mineral in enamel during in vitro
      demineralization and the gain during subsequent remineralization. Although there
      are currently relatively few centres carrying out this work, interest in the
      technique is rapidly growing and it is likely to find a useful place both in
      research and ultimately in clinical practice.

PMID- 8870057
TI  - The intra- and interobserver variability of impedance cardiography in patients at
      rest and during exercise.
AB  - We studied the intra- and interobserver variability in the calculation of stroke
      volume by the impedance technique, using the recently proposed refinements in the
      electrode configuration and signal processing. Three groups of patients were
      included in this study: ten stable cardiac patients who underwent a diagnostic
      heart catheterization, ten patients 24-26 h after coronary artery bypass surgery
      and ten patients with severe chronic obstructive pulmonary disease (COPD). The
      first two groups were studied at rest and the COPD group during submaximal
      exercise. The intra-observer variability was 4.2%, 3.9-4.0% and 6.0-6.9% for the
      catheterized, surgical and COPD groups, respectively. The interobserver
      variability was 4.3%, 2.6% and 2.4%, respectively. It is concluded that highly
      reproducible data can be obtained with the newly proposed impedance technique in
      patients at rest and exercise which may be comparable or superior to other
      techniques used in clinical settings.

PMID- 8870056
TI  - Estimation of arterial blood pressure variability by spectral analysis:
      comparison between Finapres and invasive measurements.
AB  - In order to assess the accuracy of spectral analysis of beat-by-beat arterial
      blood pressure fluctuations recorded by the finger technique we analysed
      simultaneous ipsilateral resting sequences (180 s) of systolic blood pressure
      (SP) and diastolic blood pressure (DP) obtained by brachial artery cannulation
      and by the Finapres device in 26 post-myocardial infarction (post-MI) and 24
      chronic heart failure (CHF) patients. We estimated: (i) the total variability and
      the power in the bands 0.01-0.04 Hz (band 1), 0.04-0.07 Hz (band I), 0.07-0.15 Hz
      (band III) and 0.15-0.45 Hz (band IV); and (ii) the group-average transfer
      function between the invasive and non-invasive channel. The total variability of
      intra-arterial SP was greatly enhanced by the Finapres device in both populations
      (p < 0.01) mainly due to the increase of power in bands I and II (mean percentage
      errors 157 and 111% in post-MI and 368 and 245% in CHF patients respectively).
      The power in band IV was significantly reduced in post-MI (p < 0.001) but not in
      CHF patients. The total DP variability increased in post-MI patients (p < 0.001)
      due to the increase in bands I and II (mean percentage errors 62 and 43%
      respectively). No significant difference was found in bands III and IV of the
      same group and in the overall variability of CHF. Linear system analysis showed
      that intra-arterial SP oscillations in both groups are amplified by the Finapres
      device in bands I and II, with a higher gain in CHF patients, whereas they are
      attenuated in band IV. Band III acts as a transition band. DP oscillations
      recorded non-invasively are slightly amplified in bands I and II of post-MI
      patients only and are attenuated in band IV of both groups. A substantial
      fraction (approximately 30%) of the non-invasive SP variability in band I cannot
      be explained as a pure linear transformation (amplification) of the invasive
      signal. A phase delay in the range 7 degrees-10 degrees relates the non-invasive
      signal to the invasive one in the region 0.025-0.17 Hz and approaches zero
      elsewhere. Several mechanisms were examined as potential causes of the invasive
      non-invasive differences. We argue that these differences are mainly due to the
      complex rhythmic behaviour of peripheral resistance vessels.

PMID- 8870058
TI  - Improvement of cardiac imaging in electrical impedance tomography by means of a
      new electrode configuration.
AB  - Until now, electrical impedance tomography (EIT) has been used for cardiac
      imaging with the electrodes attached transversally at the level of the fourth
      intercostal space at the anterior side. However, the results obtained with this
      electrode configuration have been disappointing. The aim of the present study was
      to improve the measurement design of EIT for cardiac imaging. Therefore, magnetic
      resonance imaging (MRI) scans were analysed in two healthy subjects to determine
      the optimum anatomical plane in which atria and ventricles are clearly visually
      separated. From these findings, we proposed a new oblique plane at the level of
      the ictus cordis anteriorly and 10 cm higher posteriorly. EIT pictures obtained
      in the oblique plane revealed a better visual separation between the ventricles
      and atria than with the electrodes attached in the transverse plane. Comparison
      between volume changes measured by means of MRI and impedance changes in
      different regions of interest measured with EIT were performed with the
      electrodes in the proposed oblique plane. Ventricular and atrial volume changes
      measured by MRI show the same pattern as do impedance changes measured by EIT.
      Furthermore, we assessed the reproducibility and validity of the oblique
      electrode configuration in ten healthy mate volunteers during rest and during
      exercise compared with the currently used transverse electrode configuration. The
      reproducibility coefficient assessed from repeated measurements with the
      electrodes attached in the oblique plane was 0.98 at rest and 0.85 during
      exercise. For the transverse plane the reproducibility coefficient was 0.96 at
      rest and 0.66 during exercise. The well-known increase in stroke volume during
      exercise is 40% in healthy subjects. The increase in impedance change during
      exercise compared with rest was 34 +/- 13% (20-59%) for the oblique plane and 68
      +/- 57% (13-140%) for the transverse plane. From these results we infer that the
      stroke volume is assessed more accurately by using the oblique plane. From these
      findings, we conclude that the oblique plane improved the cardiac measurements,
      because (i) a better spatial separation of the heart compartments is obtained,
      (ii) the results are more reliable and (iii) measurements during exercise are
      more accurate with the electrodes attached in an oblique plane.

PMID- 8870059
TI  - 3D object localization using EIT measurements at two levels.
AB  - Electrical impedance tomography (EIT) is designed essentially for two-dimensional
      imaging, but current flow in the third dimension causes images to be formed for
      objects in 3D. The present work has shown that the image of an object is shifted
      in position towards the centre almost linearly with the 3D distance from the
      electrode plane and that the slope of this linear variation depends on the radial
      distance of the object. An empirical curve has been fitted to this dependence,
      based on which a method has been developed to locate 3D point objects from EIT
      measurements in only two planes. This will be useful in clinical and other
      applications in which 3D objects are few and widely separated. This new
      methodology may be the basis for 3D imaging in the future.

PMID- 8870060
TI  - The effect of fracture and fracture fixation on ultrasonic velocity and
      attenuation.
AB  - Measurement of the velocity of propagation and attenuation of ultrasound (200
      kHz) is believed to be a useful non-invasive technique for assessing the
      mechanical properties of bone. A new method for the determination of ultrasound
      velocity and attenuation of longitudinal waves in cortical bone was used in vivo
      and in situ on intact and fractured human tibiae. The measured ultrasound
      attenuation and velocity were found to be unaffected by the soft tissue between
      transducers and bone. The ultrasound velocity in vivo on control tibiae was 3614
      +/- 32 m s-1 and the attenuation was 5.52 +/- 0.43 dB MHz-1 cm-1. The ultrasound
      velocity in fractured tibiae was considerably lower 1 week after fracture (2375
      +/- 82 m s-1), but had significantly increased after 3 weeks (to 2882 +/- 90 m s
      1). A higher attenuation was measured 1 week after fracture (17.81 +/- 3.91 dB
      MHz-1 cm-1), but it had decreased again 3 weeks after fracture (10.42 +/- 3.56 dB
      MHz-1 cm-1). In situ studies under well-defined conditions confirmed the in vivo
      results. The effects of internal plate fixation and gradually cutting through the
      cortex on the ultrasound velocity and attenuation were studied in situ. These
      results demonstrate the clinical potential of this technique for the non-invasive
      assessment of bone fracture healing.

PMID- 8870061
TI  - Analysis of the dynamics of renal vascular resistance and urine flow rate in the
      cat following electrical stimulation of the renal nerves.
AB  - In ten sino aortic denervated, vagotomized and aneasthetized cats, renal efferent
      nerves were stimulated for 30 s with trains of constant current pulses at
      frequencies in the range 5-30 Hz. The arterial pressure, heart rate, urine flow
      rate (electronic drop counter) and renal blood flow (electromagnetic technique)
      were recorded. Subsequent computer processing gave the true means of renal artery
      pressure (MRAP) and renal blood flow (MRBF) and hence the renal vascular
      resistance (MRVR), over each cardiac cycle. Recovery of MRVR after the end of
      stimulation exhibited two distinct time constants. The fast component had a time
      constant of 2.03 +/- 0.26 s and represented 60.2 +/- 1.71% of the recovery. The
      time constant of the slower component was 14.1 +/- 1.9 s and represented 36.0 +/-
      1.6% of the recovery. The relationship between MRVR and stimulus frequency was
      sigmoidal with maximum sensitivity at stimulus frequencies of 12.6 +/- 0.76 Hz.
      Changes in urine flow rate, in contrast, followed a hyperbolic function with
      maximum response sensitivity occurring at very low stimulus frequencies. Changes
      in urine flow rate were 50% complete at stimulus frequencies of 5 Hz.
      Identification of two distinct components in the relaxation phase of renal
      vascular resistance leads to a reasonable hypothesis that 60% of total renal
      vascular resistance may lie proximal to the glomerulus, whereas 36% may be
      accounted for by the efferent arterioles.

PMID- 8870062
TI  - Neurobiology of chronic fatigue syndrome.
AB  - 1. Chronic fatigue syndrome (CFS) is characterized by a new onset of significant
      fatigue for a period of six months or longer usually following an infection,
      injury or period of high stress. 2. The exact etiology of CFS is not known and a
      diagnostic test is not available. Hence, the diagnosis is made by exclusion of
      other explanations for the patient's symptoms and by meeting the CDC research
      case definitions. Early studies supported an infectious or immune dysregulation
      hypothesis for the pathophysiology of CFS. 3. Subsequent studies documented that
      neurological, affective and cognitive symptoms also occur at high rates in CFS
      patients. Neuropsychological, neuroendocrine studies and brain imaging have now
      confirmed the occurrence of neurobiological abnormalities in most patients with
      CFS. 4. In this article, the authors review these findings in relation to the
      clinical neurobiology of CFS and their potential relevance to biological
      psychiatry.

PMID- 8870063
TI  - Comparing the role of metabotropic glutamate receptors in long-term potentiation
      and in learning and memory.
AB  - 1. Neuronal plasticity has been suggested to be the physical substrate for
      changes underlying the expression of memory. One model which has attracted wide
      attention as a possible candidate of such neuronal plasticity is long-term
      potentiation (LTP), mainly investigated in the hippocampus of rodents. Moreover,
      various processes with different time constants may underlie LTP, and these
      phases show striking correspondence to different phases of memory. 2.
      Pharmacological evidence strongly implicates that the neurotransmitter glutamate
      plays a major role in LTP. Although the involvement of ionotropic glutamate
      receptors has been proven, the role of the newly discovered metabotropic
      glutamate receptors is still uncertain. 3. Metabotropic glutamate receptors
      (mGluRs) comprise a whole family with currently eight members grouped into three
      classes according to their amino acid sequence identity and pharmacological
      profile. They are G-protein coupled, either positively linked to phospholipase C
      (class I) or negatively linked to adenylate cyclase (class II and III), and among
      other effects are known to induce phosphorylation of ionotropic glutamate
      receptors as well as modulate the excitability of neurons. Finally, they are
      heterogeneously distributed throughout the brain. 4. In hippocampal slice
      preparations, mGluRs have been shown to be involved in the induction of LTP in
      CA1 and dentate gyrus by some investigators, but others have failed to reproduce
      such experiments, leaving the question: what are the appropriate conditions for
      mGluR-mediated LTP? 5. In vivo, metabotropic receptor antagonists have been shown
      to block, and agonists to facilitate, induction and maintenance of LTP, mainly at
      perforant path/dentate granule cell synapses. As demonstrated in behavioral
      investigations, mGluRs apparently play an important part in hippocampus-dependent
      learning paradigms. As in LTP, antagonists block memory formation; in contrast to
      LTP, agonists also prevent memory formation. In memory recall metabotropic
      receptors seem to play no role. 6. Based on current information the authors
      develop models for a role of mGluRs in both LTP and memory formation. Activation
      of metabotropic receptors plays a particular modulatory role when high frequency
      stimulation is weak. Strong tetanization may bypass mGluRs by stimulating other
      systems leading to, at least phenomenologically, similar LTP, Behaviorally,
      mGluRs possibly set the signal to noise ratio of the hippocampal circuit.

PMID- 8870064
TI  - Risperidone antagonism of self-mutilation in a Lesch-Nyhan patient.
AB  - 1. The case is described of a 28-year old male with a diagnosis of Lesch-Nyhan
      syndrome. 2. Chronic treatment with the atypical neuroleptic risperidone at 4 mg
      daily has maintained a significant reduction in occurrence of self-mutilation.

PMID- 8870066
TI  - Acute stimulant response prediction of chronic trazodone effects.
AB  - 1. Depressed patients who acutely improve after taking a stimulant drug have a
      better eventual response to chronic antidepressant treatment than do stimulant
      non-responders. Unlike the stimulants and most antidepressants, trazodone (TRZ)
      is not a potent monoamine reuptake inhibitor. 2. The authors tested the
      hypothesis that acute methylphenidate (MPH) and d-amphetamine (d-AMP) response
      would not correlate with eventual trazodone response because its site of action
      was different from other antidepressants. 3. It was found that acute MPH-induced
      improvement correlated with eventual TRZ-induced improvement to a limited degree.
      4. This correlation might reflect serotonin reuptake inhibition by trazodone and
      suggests that this effect is therapeutically relevant.

PMID- 8870065
TI  - Obsessive compulsive disorder and depression--first results of a prospective
      study on 74 patients.
AB  - 1. Seventy-four patients who met DSM-III-R criteria for Obsessive Compulsive
      Disorder received a serotonin reuptake inhibitor and cognitive behavior therapy
      for 6 months (baseline to follow-up I). 2. In order to maximize therapeutic
      effects, different kinds of treatment were applied between follow-up I and follow
      up II (12 months). 3. Patients were followed-up twice with respect to long-term
      outcome of obsessive compulsive disorder and depression. Forty % of the sample
      showed marked improvement at follow-up. No specific variant of treatment could be
      identified to be significantly more effective. 4. Cross-sectional investigations
      showed significant correlations between extent of depressive and obsessive
      compulsive symptomatology (admission, follow-up I and II).

PMID- 8870067
TI  - Effect of isolation on morphine-induced running and changes in body temperature.
AB  - 1. The influence of isolation of three durations 8, 15 and 30 days has been
      examined in mice on the effects of morphine on rectal temperature and on
      locomotor activity. Isolated mice were compared to non isolated mice with the
      same age. 2. Morphine (20 mg/kg ip) induced in mice an early hypothermia followed
      by a late hyperthermia. The hypothermic effect was significantly reduced
      following isolation, but the duration of isolation (8, 15, 30 days) had no
      influence. Isolation did not modify the hyperthermic effect of morphine. 3.
      Morphine (40 mg/kg ip) induced in mice an increase in locomotor activity called
      "running". The running activity was significantly increased following isolation.
      The duration of isolation (8, 15, 30 days) did not seem to influence this effect.
      4. These results show that isolation does not modify in the same way every
      effects of morphine, they suggest that isolation alters the mechanism involved in
      the running activity and in the hypothermic effect. The nature of these
      mechanisms is discussed.

PMID- 8870068
TI  - The effects of cocaine and nandrolone co-administration on aggression in male
      rats.
AB  - 1. Cocaine and anabolic-androgenic steroids are among the more commonly abused
      substances in selected populations. These agents, when used alone or in
      combination, have been reported to cause aggressive tendencies in both laboratory
      based animal models and in human clinical situations. This project, using a
      resident-intruder paradigm, examined the effects of co-administration of cocaine
      and a typical anabolic-androgenic steroid, nandrolone decanoate, on the
      development of aggression in male Sprague-Dawley rats. 2. Dose response studies
      demonstrated that low dose cocaine (1 mg/kg) produced more aggression in a
      greater percentage of animals than for either the controls or groups receiving
      higher doses (up to 20 mg/kg). Initially, high intermittent doses of nandrolone
      (20 mg twice weekly) produced more aggression; however, low daily doses of
      nandrolone (2 mg) produced greater levels of aggression following 4 weeks of
      treatment. 3. Optimal doses of cocaine and nandrolone, when administered
      together, resulted in aggression scores that were not significantly different
      from controls or either drug singly. However, a greater percentage of animals
      receiving both drugs exhibited aggression than did rats receiving either drug
      alone. 4. These results support the interpretation that the drugs interact to
      produce unique effects in the development of aggression. However, the complexity
      and extent of the interactions is great and remains to be fully elucidated.

PMID- 8870069
TI  - Ibogaine fails to interrupt the expression of a previously established one-trial
      morphine place preference.
AB  - 1. Ibogaine, a proposed anti-addictive agent, has been found to interfere with
      the acquisition of a weak morphine-induced place preference. The present series
      of experiments determined if ibogaine would interfere with the expression of a
      previously established morphine (5 mg/kg) place preference. 2. A single injection
      of 40 mg/kg of ibogaine 24 h, 12 h or 4 h prior to the preference test
      (Experiment 1) or 80 mg/kg of ibogaine 24 hr prior to the preference test
      (Experiment 3) did not interfere with the expression of a morphine conditioned
      place preference. 3. Furthermore, two injections of 40 mg/kg of ibogaine 48 h and
      24 h or 24 h and 4 h prior to testing (Experiment 2) did not interfere with the
      expression of a morphine place preference. 4. Ibogaine appears to be incapable of
      attenuating the expression of a previously established one-trial morphine place
      preference.

PMID- 8870070
TI  - Effect of aging on the spatial learning deficit produced by diazepam in rats.
AB  - 1. After pretraining in an undrugged state, young (6 months) and aged (18-24
      months) rats were trained on a spatial learning-set task after receiving one of
      four doses of diazepam (1, 2, 3 or 5 mg/kg) or the drug vehicle. The effects of 5
      mg/kg of diazepam were also assessed on the spatial learning-set task one full
      hour after injection (delay condition) as well as on the visible platform task.
      2. During pretraining (undrugged), aged rats demonstrated a transient impairment
      on the visible platform task but subsequently did not differ significantly from
      young rats on the submerged platform task. On the spatial learning-set task, aged
      rats performed as well as young rats under control conditions and diazepam
      produced a comparable dose-dependent impairment of spatial learning. However,
      when the 1 hr delay was interposed between diazepam administration and maze
      testing, only aged rats exhibited a spatial learning impairment. Diazepam did not
      impair performance on the visible platform task in either young or aged rats. 3.
      These results indicate that although the amnesic effect of diazepam is not
      initially greater in aged rats, it persists for longer periods.

PMID- 8870071
TI  - Effects of convulsant and anticonvulsant agents on memory in squirrel monkeys.
AB  - 1. It has been reported that subconvulsive doses of convulsant agents such as
      strychnine and pentylenetetrazole can enhance memory in rodents studied under
      various behavioral procedures. The present study was designed to determine if
      similar results might be obtained in squirrel monkeys. 2. Responding by squirrel
      monkeys was maintained by food presentation under a repeated acquisition of
      behavioral chains procedure. Each subject acquired a different three-response
      chain each session. 3. Sequence completions were reinforced under a fixed-ratio 5
      schedule (FR 5) and errors produced a brief timeout. After the subject reached a
      predetermined acquisition criterion, the session was stopped and a 24 hr delay
      was interposed. Following the delay, the subject was retested on the same
      discrimination and retention was quantified as percent savings. 4. When
      administered immediately after the subject reached the acquisition criterion,
      strychnine (0.0056 -0.18 mg/kg) and pentylenetetrazole (0.32-42 mg/kg) neither
      enhanced nor disrupted percent savings under the 24 hour delay. Similarly, the
      delta opioid agonist, BW373U86 (0.0056-3.2 mg/kg) [(+/-)-4 -((alpha-R*)-alpha
      ((2S*,5R*)-4-allyl-2,5-dimethyl -1-piperazinyl)-3-hydroxybenzyl)-N,N
      diethylbenzamide dihydrochloride], had little or no effect on percent savings
      following a 24 hr delay. This was true even at doses of BW373U86 which produced
      convulsions. In contrast, triazolam (1-1.8 mg/kg) decreased percent savings
      following the 24 hr delay at doses which had little or no effect on response
      rate. 5. These results suggest that at subconvulsive doses, convulsant agents
      have little or no effect on memory storage, while at higher doses agents such as
      triazolam can disrupt memory processes in squirrel monkeys.

PMID- 8870072
TI  - Structure and distribution of modules in extracellular proteins.

PMID- 8870073
TI  - Role of uncoupled and non-coupled oxidations in maintenance of safely low levels
      of oxygen and its one-electron reductants.

PMID- 8870074
TI  - Coordination of nuclear and cytoplasmic oocyte maturation in eutherian mammals.
AB  - As oocytes near the end of their growth phase, they become competent to undergo
      two aspects of maturation, cytoplasmic and nuclear. Both are essential for the
      formation of an egg having the capacity for fertilization and development to live
      offspring. Nuclear maturation encompasses the processes reversing meiotic arrest
      at prophase I and driving the progression of meiosis to metaphase II. Cytoplasmic
      maturation refers to the processes that prepare the egg for activation and
      preimplantation development. This review focuses on the developmental programmes
      whereby oocytes at the germinal vesicle (GV) stage acquire competence to undergo
      nuclear and cytoplasmic maturation, the coordination of programmes regulating the
      acquisition of these competencies in GV-stage oocytes, and the coordination of
      the maturational processes themselves. Although the developmental programme of
      the GV-stage oocyte for acquiring competence to complete preimplantation
      development does not appear to be tightly linked to the acquisition of competence
      to complete nuclear maturation, GV breakdown (GVB) is probably essential for
      activating some critical aspects of cytoplasmic maturation, particularly those
      related to fertilization and activation. Nuclear and cytoplasmic maturation are
      normally coordinated by this mechanism requiring the mixing of the GV contents
      with the cytoplasm at the time of GVB, but some processes of cytoplasmic
      maturation related to successful preimplantation development probably still occur
      without coordination with nuclear maturation. Thus, continued differentiation of
      GV-stage oocytes is necessary after the acquisition of competence to undergo
      nuclear maturation, to allow for the deposition of the maternal factors required
      for the development of preimplantation embryos beyond the 2-cell stage.

PMID- 8870075
TI  - Mammalian oocyte organelles with special reference to pleomorphic mitochondria
      and vacuole formation in marsupials.
AB  - Marsupial oocytes are larger and have a thinner zona than eutherian oocytes; and
      the ooplasm becomes almost completely filled with empty-looking vacuoles the
      contents of which have, so far, defied histochemical analysis. In the opossum,
      Monodelphis domestica, apart from orthodox mitochondria, a 'hooded' form is found
      occasionally in young primary oocytes, and a novel 'spiked' form-which is very
      elongate and has longitudinally-running filaments attached to the outer membrane-
      is found in mature oocytes. On the genesis of the ooplasmic vacuoles in mammals,
      information is available only for two marsupials. In Monodelphis, the vacuoles
      originate from endoplasmic, endocytotic and Golgi vesicles which generate
      multivesicular bodies; these give rise to the vacuoles. For the bandicoot,
      Isoodon macrourus, evidence is presented for the formation of the vacuoles from
      enlarged, transformed mitochondria which undergo a complex evolution during
      development. Primordial oocytes of Isoodon contain three ooplasmic localizations-
      a paranuclear complex, a vesicle microtubule complex and an aggregate of tubular
      cistenae-which have not been described for other mammalian oocytes. The origin,
      fate and function of these organelle localizations is unknown. In this paper,
      problems with respect to the definition of 'yolk' are described and the extent of
      our ignorance concerning oocyte organelles is discussed.

PMID- 8870076
TI  - Cytoplasmic maturation of the marsupial oocyte during the periovulatory period.
AB  - During the period immediately before ovulation, the oocytes of most eutherian and
      marsupial mammals complete the first meiotic maturation division and extrude the
      first polar body. In marsupials, this phase of nuclear maturation is accompanied
      by an increase in size of the egg and maturation of cytoplasmic components.
      Oocytes from at least four marsupial species, Trichosurus vulpecula, Macropus
      eugenii, Bettongia penicillata and Monodelphis domestica, continue to grow after
      formation of the follicular antrum and, although the rate of growth slows in
      larger follicles, it continues into the period immediately before ovulation. The
      basis of this growth is unknown but may include accumulation of fluid and/or yolk
      like material. Maturational changes within the cytoplasm of the oocyte also occur
      during the periovulatory period, including the accumulation of cortical granules.
      Differences in the structure of the zona pellucida are also evident between
      follicular and ovulated eggs; these differences are suggestive of compression of
      the zona pellucida, but may involve the addition of extra material. These
      findings suggest that the marsupial oocyte may not achieve complete cytoplasmic
      maturity until after ovulation; however, their relevance to fertilization and
      embryonic development require further investigation. Like those of eutherian
      mammals, marsupial oocytes undergo spontaneous nuclear maturation once removed
      from the follicular environment, suggesting a basically similar control system.
      It is not known whether the preovulatory cytoplasmic changes seen in marsupial
      oocytes matured in vivo also occur during maturation in vitro.

PMID- 8870077
TI  - A comparison of oocyte organelles in Monodelphis domestica with those of other
      marsupials and eutherians.
AB  - This paper reviews the current knowledge of oocyte cytology in marsupials,
      particularly Monodelphis domestica, and eutherian mammals. Some of the
      conspicuous features will be described and their function discussed. Despite many
      fundamental similarities between the oocytes of eutherian mammals and marsupials,
      some aspects are different (e.g. growth pattern, final size, timetable of
      cytoplasmic maturation and utilization of storage material during early cleavage
      stages), when most of the vesicles are extruded into the perivitelline space in
      marsupials.

PMID- 8870078
TI  - Culture of preantral ovarian follicles in the grey, short-tailed opossum,
      Monodelphis domestica.
AB  - A culture system designed to support the development of individual preantral
      mouse ovarian follicles has been employed to study follicle growth in the New
      World marsupial species Monodelphis domestica. Preantral follicles were isolated
      mechanically and cultured individually in microdrops under oil. Preliminary
      results indicate that follicle growth was positively correlated to the
      concentration of follicle-stimulating hormone (FSH) provided, with 1.0-1.5 IU FSH
      mL-1 producing the best results. Incubation at the body temperature of M.
      domestica (33 degrees C) was found to be preferable to that at 37 degrees C. The
      culture system was able to support follicle growth; however, despite follicles
      exceeding the size when antrum formation occurs in vivo, they remained preantral.

PMID- 8870079
TI  - A light microscopic study of oogenesis in the brushtail possum Trichosurus
      vulpecula.
AB  - Ovaries from young of the brushtail possum, Trichosurus vulpecula, were examined
      histologically and histochemically to determine stages of oogenesis. Groups of
      dividing oogonia were first present in a 13-day-old pouch young, with extensive
      oogonial proliferation after about 23 days of age. Meiosis was initiated in some
      oogonia by 48 days of age, and by 88 days numerous early primordial follicles
      were present. The first primary follicles had formed by 103 days of age. In
      oocytes of quiescent primordial follicles, dark granular material, which stained
      positively for protein, mainly occupied the perinuclear cytoplasm. Associated
      with the transition to primary follicles and continuing throughout oocyte growth
      was the production within the central cytoplasm of large clear vesicles and, to a
      lesser extent, lipid-like yolk bodies. The former were analogous to similar
      vesicles found in other species of marsupial, and have a putative role in
      development of the blastocyst. By contrast, yolk-like bodies are not found in all
      marsupial oocytes and their importance in development is unknown.

PMID- 8870080
TI  - Regulation of the motility and metabolism of spermatozoa for storage in the
      epididymis of eutherian and marsupial mammals.
AB  - The present review examines the mechanisms involved in sperm storage in the
      epididymis of therian mammals in terms of the supply of energy substrate and the
      regulation of motility and metabolism. Lipids, glucose, lactate and glycerol are
      possible metabolic substrates for sperm in the epididymis, but the role of these
      is uncertain and it may differ between marsupials and eutherians. Sperm are
      normally immotile in the epididymis, but ram and rabbit sperm may have an
      uncoordinated motility. Sperm metabolism is suppressed but is probably not
      strongly coupled to motility. Work on diluted sperm indicates that cyclic
      adenosine monophosphate, Ca2+, and pH play roles as intracellular messengers
      controlling the motility and metabolism of sperm, but no first messenger has been
      identified. A number of mechanisms of suppressing sperm motility and metabolism
      in the epididymis are considered, including a collective autoregulation, oxygen
      tension, osmotic pressure, viscosity and the extracellular concentration of H+,
      Ca2+, Na+, HCO3- and carnitine. However, there is no conclusive evidence for any
      of the mechanisms and there is clearly some variation between species in the
      mechanism of suppressing sperm activity. Sperm activation stimulates motility and
      a 4-5-fold increase in respiration rate that has not been reversed without
      compromising viability. Following activation, respiration supported by endogenous
      and/or exogenous substrates is much higher in marsupial than eutherian sperm, and
      marsupial sperm do not show a large stimulation of respiration on the addition of
      exogenous substrate, as is characteristic of most eutherian sperm.

PMID- 8870081
TI  - What marsupial gametes disclose about gamete function in eutherian mammals.
AB  - The gametes of eutherian mammals present some fundamental enigmas in regard to
      their structure and behaviour that have not been solved by a focus on the
      Eutheria alone. Although the evidence is limited still, some clues are suggested
      in comparison with representative American and Australian marsupials, whose
      gametes have undergone parallel, although sometimes quite different, evolutionary
      changes to those of eutherian mammals. The contrasts between them illuminate
      basic questions about the functions of the epididymis and sperm capacitation,
      about sperm numbers and sperm production, about the function of the cumulus
      oophorus and the configuration of the Fallopian tube and, not least, about gamete
      design and its bearing on the mechanisms by which spermatozoa penetrate the egg
      coat.

PMID- 8870082
TI  - Capacitation mechanisms, and the role of capacitation as seen in eutherian
      mammals.
AB  - Capacitation, the process whereby spermatozoa are rendered capable of interacting
      with and fertilizing the egg, was discovered more than 40 years ago. However, our
      understanding of it is still far from satisfactory. Several factors conspire to
      obfuscate studies of capacitation mechanisms: the inherent functional
      heterogeneity of sperm populations, the range of functions used as parameters of
      capacitation (whence the endpoint of the process has become conceptually
      uncertain), and the several profound differences between model in vitro
      fertilization (IVF) systems and the situation in vivo in the female reproductive
      tract. Recent investigations in the author's laboratory have shown that
      bicarbonate/CO2, an essential component for successful IVF, causes rapid changes
      in lipid architecture of the sperm plasma membrane and slower changes in surface
      coating. These changes are accompanied by membrane destabilization and cell
      death. Evidence suggests that bicarbonate's actions are mediated through cyclic
      nucleotide signalling. Of particular note is the heterogeneity in rate of
      response to bicarbonate shown by individual cells in the sperm populations. Taken
      together with other observations, the findings suggest that capacitation is a
      series of positive destabilizing events that eventually lead to cell death. The
      'capacitated' state would then be a window of destabilization within which
      spermatozoa can undergo a zona-induced acrosome reaction and display
      hyperactivated motility. Further along the destabilization pathway, spontaneous
      acrosome reactions would occur before total membrane degeneration. In vivo,
      capacitation would be a conflict between destabilization and sperm survival.
      Concentrations of bicarbonate are maintained low in the cauda epididymidis, where
      sperm survive for long periods, and one may speculate that hormonal control of
      local bicarbonate/CO2 in oviducal 'storage' sites in the female tract could allow
      'safe' sequestering of live spermatozoa until around the time of ovulation; the
      environment may then change to produce a 'capacitating' effect, whence, due to
      the inherent functional heterogeneity of the sequestered population, small
      numbers of capacitated spermatozoa are released sequentially. In this way, a
      succession of spermatozoa in the correct physiological state may be provided for
      the freshly ovulated egg.

PMID- 8870083
TI  - Capacitation and the acrosome reaction in marsupial spermatozoa.
AB  - Although yet to be established definitively, it appears that marsupial
      spermatozoa require a process of capacitation and that the mechanisms involved
      may be quite different between the Australian and American species. For
      Australian species, failure to induce this functional event in culture has meant
      that in vitro fertilization (IVF) is yet to be achieved. However, in the American
      species with paired spermatozoa, IVF and subsequent embryo development have been
      obtained under quite simple culture conditions. Our understanding of the
      interactions of marsupial spermatozoa with the female tract, and in particular
      the oviduct, the most likely site of capacitation, is discussed. Although the
      acrosome reaction (AR) is an equally critical event in marsupial fertilization it
      appears to be regulated quite differently. The uniquely stable character of the
      marsupial acrosome is examined as well as our current understanding of the
      regulation of the marsupial sperm AR in vivo and in vitro.

PMID- 8870084
TI  - Gamete biology of the new world marsupial, the grey short-tailed opossum,
      Monodelphis domestica.
AB  - Mammalian gametes undergo a series of functional and developmental changes that
      culminate in fertilization. In order to appreciate the necessity for such complex
      processes as sperm maturation, capacitation and the intimate sperm-egg
      interactions leading to gamete fusion, it is important to understand how gametes
      may have evolved. In this respect, marsupials are particularly relevant since
      they exhibit features reminiscent of both non-mammalian vertebrates and eutherian
      mammals. The grey short-tailed opossum, Monodelphis domestica, is a New World
      marsupial from Brazil. It breeds well under laboratory conditions and is an
      excellent animal model to investigate marsupial gamete biology. As in other
      American marsupials, the spermatozoa of the opossum form pairs in the epididymis.
      Here, a number of studies carried out in this laboratory, related to sperm
      maturation, capacitation and fertilization in M. domestica, are reviewed and the
      gamete biology in this species is compared with what is known in other marsupials
      and eutherian mammals.

PMID- 8870086
TI  - Variation in ultrastructure of mucoid coat and shell membrane secretion of a
      dasyurid marsupial.
AB  - In the dasyurid marsupial Sminthopsis crassicaudata, the shell membrane of
      cleaving embryos has a compact granular structure but becomes fibrous around
      blastocysts. Polyclonal antibodies were raised against the extracellular coats,
      mucoid and shell membrane, of oocytes and early embryos. Immunogold cytochemistry
      resulted in labelling of secretory granules in the epithelia of both the ampulla
      and isthmus of the oviduct, although the secretory granules of these two regions
      differed in their ultrastructural appearance. Those in the ampulla were
      heterogeneous with areas of varying electron density, whereas those in the
      isthmus were electron dense and homogeneous. Shell membrane precursors were found
      in secretory granules in the epithelia of the uterotubal junction and endometrial
      glands and were electron lucent.

PMID- 8870085
TI  - Egg maturation and fertilization in marsupials.
AB  - This brief review summarizes our knowledge of the morphological events that are
      associated with oocyte maturation and fertilization in marsupials in which it has
      been suggested that there are marked differences from eutherians in both the
      developmental timetable of oocyte maturation and in some of the processes
      associated with sperm-egg interaction. Most of the data have been obtained from
      studies on four species: Monodelphis domestica, Sminthopsis crassicaudata,
      Sminthopsis macroura, and Trichosurus vulpecula. Differences between the species
      have been described for: (1) the arrangement of 'yolk' in the oocyte cytoplasm;
      (2) the time of formation of cortical granules: (3) the mode of sperm penetration
      through the zone pellucida: (4) the sperm membrane involved in sperm-egg fusion:
      (5) the fate of inner acrosomal and sperm plasma membranes: and (6) the rapidity
      of sperm chromatin decondensation in the ooplasm. Such differences suggest
      considerable variation in these processes between different marsupial species
      although some of the variation described may be due to technical differences in
      the obtaining of the data. Thus, whether there are fundamental differences
      between the two major extant infraclasses of mammals, marsupials and eutherians,
      in some of the processes associated with fertilization is conjectural at the
      present time. The interspecific variation in the results obtained cautions one in
      extrapolating from observations on one or two 'model' species to the infraclass
      as a whole: a conclusion that might not, on reflection, be too surprising bearing
      in mind the long and separate evolutionary history of the major extant marsupial
      lineages.

PMID- 8870087
TI  - Possum biocontrol: prospects for fertility regulation.
AB  - Research has begun recently into biocontrol of brushtail possums as the only long
      term, cost-effective solution to the possum problem in New Zealand, where possums
      cause significant damage to native forests, threaten populations of native plants
      and animals, and infect cattle and deer with bovine tuberculosis. Fertility
      regulation as a means of biocontrol has the support of major animal welfare and
      conservation groups in New Zealand. Systems are being investigated, mostly in
      reproduction and development, with the ultimate aim of developing immunologically
      based fertility regulation (immunocontraception), but much basic information
      essential to such an approach for possums is lacking. The key components for the
      success of this approach--suitable vectors expressing possum-specific
      reproductive antigens sufficiently to block reproduction--are reviewed. The
      social and political issues of local, national and international risk and
      acceptability arising from such an approach are also discussed.

PMID- 8870088
TI  - Hormones of oestrus and ovulation and their manipulation in marsupials.
AB  - Oestrus and ovulation occur spontaneously in the majority of marsupials, with
      behavioural oestrus usually occurring 1-2 days before ovulation. The hormone
      changes that occur at this time have been described in the most detail for the
      monovular tammar wallaby Macropus eugenii. The respective roles of the Graafian
      follicle, corpus luteum and the pituitary in the events leading up to oestrus and
      ovulation in this species are also reviewed. Recently, various protocols have
      been developed for superovulation of marsupials, including Australian species,
      such as the brush-tailed possum, fat-tailed dunnart, brush-tailed bettong and
      tammar wallaby, and the American laboratory opossum, Monodelphis domestica. These
      protocols provide an opportunity for studying the regulation of ovarian activity
      and for the collection of larger quantities of material for the study of gamete
      maturation, in vitro fertilization and embryonic development.

PMID- 8870089
TI  - Effect of cooling and cryopreservation on sperm motility and morphology of
      several species of marsupial.
AB  - The effects of long-term cooling and freezing on sperm motility are described for
      six marsupial species: the fat-tailed dunnart, koala, brushtail possum, long
      footed potoroo, northern brown bandicoot and ring-tailed possum. The effects of
      up to eight days of cooling at 4 degrees C on the motility of dunnart spermatozoa
      and the effect of cryopreservation on spermatozoa of the other species were
      determined. The cryoprotectant used was a Tris-citrate-fructose-egg yolk-glycerol
      diluent. The percentage and rating of sperm motility, and sperm structure, as
      determined by light microscopy, were investigated. Sperm motility in the fat
      tailed dunnart was retained for up to six days when cooled to 4 degrees C,
      suggesting that sperm from this species have some degree of tolerance to cold
      shock. After this time, however, the percentage of motile spermatozoa and their
      motility rating declined. In all species except the fat-tailed dunnart,
      reinitiation of motility following cryopreservation occurred across a range of
      glycerol concentrations (4-17%). Cryoprotectant containing 6% and/or 8% glycerol
      resulted in little change of motility rating or of the percentage of live sperm
      after thawing, although there was some decline in the percentage of motile sperm.
      The unusual structural and motility characteristics of dunnart spermatozoa may
      account for the lack of success of sperm cryopreservation in this species.

PMID- 8870090
TI  - Pellet-freezing spermatozoa of two marsupials: the tammar wallaby, Macropus
      eugenii, and the brushtail possum, Trichosurus vulpecula.
AB  - A protocol was developed for pellet-freezing spermatozoa of the tammar wallaby
      and the brushtail possum. Seren was collected by electro-ejaculation and wallaby
      spermatozoa were washed by 'swim-up' into phosphate-buffered saline (PBS),
      whereas possum spermatozoa were not washed. Wallaby spermatozoa were screened for
      toxicity in diluents containing a range of cryoprotectants (0-10%): dimethyl
      sulfoxide (DMSO), ethylene glycol and propanediol. Possum spermatozoa were
      tolerant of diluents containing 17.5% glycerol. Wallaby and possum spermatozoa
      were diluted 1:1 with the most promising cryoprotective diluents (final
      concentrations in PBS: possum, 17.5% glycerol; wallaby, 7.5% glycerol + 10% DMSO)
      and, after 5 min equilibration at room temperature, were pellet-frozen. Pellets
      were thawed (35 degrees C) and wallaby spermatozoa were washed by centrifugation
      (200 g for 5 min) and resuspended in PBS to minimize cryoprotectant toxicity. A
      high proportion of possum spermatozoa was recovered after freezing (67.5%),
      having good progressive motility (3.6 on a 0-5 scale). The progressive motility
      of frozen-thawed wallaby spermatozoa was also high (3.0), but only 10% of motile
      spermatozoa were recovered. The pellet-freezing method in conjunction with the
      post-thaw washing procedure (wallaby) may produce a viable population of
      cryopreserved marsupial spermatozoa suitable for use in assisted-breeding
      techniques such as in vitro fertilization and artificial insemination.

PMID- 8870091
TI  - Nutrient uptake and culture of Sminthopsis macroura (stripe-faced dunnart)
      embryos.
AB  - Glucose and pyruvate uptake by individual embryos were measured in a marsupial
      species (stripe-faced dunnart) and a eutherian species (mouse). At each stage of
      development, nutrient uptake by the dunnart embryo was around an order of
      magnitude greater than that of the mouse embryo. The pattern of glucose uptake by
      the dunnart embryo was not like that for any eutherian embryo, all of which have
      a low glucose uptake before the blastocyst stage. Rather, in the dunnart embryo
      there was a significant increase in glucose uptake after the third cleavage
      division, increasing from 13.6 pmol embryo h-1 at the 4-cell stage to 34.9 pmol
      embryo h-1 by the 8-cell stage. This increase in glucose uptake before blastocyst
      formation may be attributed to an increased energy demand associated with the
      movement of cells within the dunnart embryo. Using a new culture system, it was
      possible to culture 66% of dunnart embryos at the 2-4-cell stage and 80% of those
      at the 8-16-cell stage to the unilaminar blastocyst stage. Embryos cultured from
      the 2-cell to the 4-cell stage were retarded by around 12 h when they reached the
      blastocyst stage. Developmental retardation was also reflected in the pattern of
      nutrient uptake, which lagged behind that of embryos developed in vivo. The
      present study has shown that it is possible to culture the early marsupial embryo
      to the blastocyst stage in a serum-free culture system, while concomitantly
      quantifying embryonic nutrient requirements. Such an approach is essential for
      species where there is a paucity of material for study.

PMID- 8870092
TI  - Origins of pluriblast and trophoblast in the eutherian conceptus.

PMID- 8870093
TI  - The blastocyst epithelium is not a protoderm in dasyurid marsupials: a review of
      the evidence.
AB  - Evidence from studies of cleavage and blastocysts in dasyurids in reviewed to
      show that the unilaminar blastocyst is not a protoderm but consists of two cell
      types. Cleavage and blastocyst formation in marsupials has been most
      comprehensively studied in dasyurids, in which the secondary oocyte and zygote
      are polarized with respect to the position of the nucleus, cytoskeletal elements
      and cytoplasmic vesicles. Polarity is reinforced by fertilization. Early cleavage
      divisions are associated with the polarized elimination of a yolk mass and many
      vesicular structures into the perivitelline space. Because secretion of the
      vesicular structures, of which several types are found, facilitate blastomere
      zona then blastomere-blastomere associations during cleavage, a unilaminar
      blastocyst forms without an intervening morula stage. Polarization of the
      cleavage cavity is related to the appearance of two cell lineages, pluriblast and
      trophoblast, at the 16-cell stage. In species in which the yolk mass persists,
      the tier of eight cells lying nearest the yolk mass forms the pluriblast (future
      embryonic and extra-embryonic lineages), and the other tier forms the trophoblast
      (future extra-embryonic ectoderm of the yolk sac). Thus, the unilaminar
      blastocyst epithelium is not a protoderm. Blastocyst expansion is associated with
      increased cell numbers mainly in the trophoblast. Pluriblast cells begin to
      increase just before the appearance of the hypoblast. The two cell populations
      can be distinguished by ultrastructural and histological features at the end of
      cleavage. During blastocyst expansion they differ in appearance and behaviour in
      vitro and in cell-doubling time. Two populations of cells have also been found in
      cleavage and unilaminar blastocyst stages in other marsupials, such as opossums,
      brushtail possums and bandicoots.

PMID- 8870094
TI  - Cleavage in vivo and in vitro in the Marsupial Macropus eugenii.
AB  - In the tammar wallaby, transport down the oviduct takes less than 24 h after
      fertilization and a mucoid coat is deposited within a few hours of fertilization,
      with excess spermatozoa trapped in the mucoid layer. The mucin coat thickens as
      the zygote passes down the oviduct. A proteinaceous shell is laid down outside
      the mucin coat in the utero-tubal region of the tract. The fertilized zygote
      enters the uterus in the pronuclear stage with cleavage proceeding in the uterus.
      In vivo, the first cleavage takes place two days post coitum (p.c.)
      (approximately 24 h after ovulation) but the next three cleavage stages may be
      completed within 24 h (between 48 h and 72 h p.c.). Thus, cell-doubling time
      appears to be around 8 h for 2-8-cell stages. Cleavage in vitro can occur with,
      or without, the shell membrane. Cleavage in early embryos of the tammar in vitro
      is slower than that occurring in vivo, and in vitro there may be a '4-cell block'
      in early development, as in dasyurids. The pattern of cleavage differs markedly
      from that of dasyurid marsupials in that there is no extrusion of yolk material
      from the cells and no separation of the blastomeres during the first cleavage
      stages to the 8-cell stage. The blastomeres are characterized by numerous
      vesicular structures and lipid droplets, but no yolk bodies. Polarity is not
      marked in early cleavage, but by the 8-cell stage polarity has developed with
      surface microvilli and numerous granular vesicles and mitochondria in the
      cortical regions at one pole of the cells, but sparse microvilli on the inner
      surfaces and at the other pole. There are complex intervillous interdigitations
      of microvilli between cells. However, clear identification of cells as pluriblast
      or trophoblast cells is not possible up to the 8-cell stage examined. These
      results demonstrate that this macropodid marsupial has a distinctive pattern of
      early development which differs from that of Didelphis and of the dasyurid
      marsupials so far described.

PMID- 8870095
TI  - The type and differentiation of cells in vitro from unilaminar and bilaminar
      blastocysts of two marsupials, Antechinus stuartii and Sminthopsis macroura.
AB  - The type and ability to differentiate in vitro of cells found in blastocysts of
      two marsupials were examined. Thirteen unilaminar blastocysts on Day 7 to Day 12
      of gestation and 24 bilaminar blastocysts on Day 16 and Day 18 of gestation were
      collected from 11 brown antechinus, Antechinus stuartii. A total of of 77
      unilaminar blastocysts on Day 5 and Day 6 of gestation and a total of 61
      bilaminar blastocysts on Day 6 and Day 7 of gestation were collected from 40
      stripe-faced dunnarts, Sminthopsis macroura. Pluriblast and trophoblast cells,
      confined to separate hemispheres, were found in unilaminar and bilaminar
      blastocysts, establishing that the blastocyst epithelium was not a protoderm.
      Hypoblast cells were found only in bilaminar blastocysts. Pluriblast and
      hypoblast cells did not differentiate or proliferate in up to eight weeks in
      culture. A small number of trophoblast cells transformed to a multinucleate state
      but the remainder did not proliferate or differentiate further. The presence of
      murine leukaemia inhibitory factor or medium conditioned by exposure to marsupial
      fibroblast feeder layer was not required for the maintenance of an
      undifferentiated state. Differentiation, proliferation and attachment of cells
      were not influenced by the presence of the yolk mass or the egg coats in culture.
      The time taken for attachment of dissociated cells varied significantly between
      cultures with no substrate and with collagen, fibronectin or laminin (P = 0.001,
      ANOVA) but did not vary significantly between substrates. The substrates did not
      influence the state of differentiation of the cells.

PMID- 8870096
TI  - Nomenclature of early development in mammals.

PMID- 8870097
TI  - Induction and differentiation of extra-embryonic mesoderm in the mouse.
AB  - Extra-embryonic mesoderm, derived at the time of gastrulation from the primitive
      streak, gives rise to several tissues that function to provide the embryo with
      nutrients, a means of waste disposal, and mechanical protection. Little is known
      about the differentiation of this tissue and about the growth and transcription
      factors involved. The present review focussed on growth and transcription factors
      that may be involved in differentiation of extra-embryonic mesoderm, and results
      from fate-mapping and transplantation studies. Methods in vitro available for
      assaying the effects of growth and transcription factors on development of extra
      embryonic development are also discussed.

PMID- 8870098
TI  - Fate-map analysis of the epiblast of the dasyurid marsupial Sminthopsis macroura
      (Gould).
AB  - Allocation of cells in the marsupial epiblast to embryonic and extra-embryonic
      domains has to date been studied only histologically. An unresolved issue in
      marsupial embryology has been the existence of a medullary plate. We re-examined
      the hypotheses that the medullary plate, or neurectoderm, arises before notochord
      formation and that the integumentary ectoderm is segregated from the ectoderm
      after the formation of the medullary plate. By marking epiblast cells in 65 Day-8
      embryos of the dasyurid marsupial Sminthopsis macroura, with the lipophilic cell
      surface marker, DiI, we demonstrated that the so-called medullary plate contains
      progenitors of the integumentary ectoderm of the neck, chest, limbs and flank of
      the embryo. Thus, cell-allocation processes in the epiblast must have segregated
      the entire complement of embryonic ectoderm in one event, not separate events. It
      is concluded that the embryonic structure called 'medullary plate' in marsupial
      embryos is misnamed since, in fact, it consists of both integumentary ectoderm
      and neurectoderm.

PMID- 8870099
TI  - Cloning, sequencing and expression of stem cell factor (c-kit ligand) cDNA of
      brushtail possum (Trichosurus vulpecula).
AB  - By means of reverse transcription polymerase chain reaction (RT-PCR), three stem
      cell factor (SCF) cDNAs (822-738 bp in size) were amplified from brushtail possum
      ovarian poly (A)+ RNA. The largest and smallest of these cDNAs were cloned and
      sequenced. Characterization of these cDNAs has revealed that possum SCF has
      approximately 75% and 66% homology to SCF of eutherian mammals at the nucleotide
      level and the predicted amino acid level respectively. Nucleotide sequencing
      shows that the 738-bp cDNA represents an mRNA splice variant, equivalent to that
      found in eutherian mammals, in which an exon (84 bp) encoding a potential
      proteolytic cleavage site is removed. Comparison of the predicted possum SCF
      amino acid sequence with the predicted SCF amino acid sequences from eutherian
      mammals reveals conservation of all cysteine residues and 3 of 4 potential N
      linked glycosylation sites. In addition, the hydropathicity profile of the possum
      SCF protein is similar to that of eutherian SCF suggesting that protein
      conformation is conserved. Northern analysis was used to characterize possum SCF
      gene expression in adult ovary and testis. A major transcript of 9 kb was
      observed in both ovarian and testicular tissue. The conservation of the SCF gene
      and its predicted protein, suggests that SCF in the possum has similar biological
      activities to SCF in eutherian mammals.

PMID- 8870100
TI  - Changes in structure of the trophectoderm of a marsupial in Mid-pregnancy up to
      the time of implantation.
AB  - Pre- and peri-implantation embryos of the dasyurid marsupial Sminthopsis
      crassicaudata were examined for morphological differentiation of the
      trophectoderm. The cells of unilaminar blastocysts were all squamous and stained
      intensely with toluidine blue. In bilaminar blastocysts and embryos at the early
      embryonic-disc stage, the trophectoderm was similar in appearance to, but stained
      more lightly than, the underlying endoderm. Trophoblast differentiation did not
      appear to occur until the mesoderm had begun to migrate between the trophoblast
      and endoderm beyond the embryonic disc. At this stage, trophoblasts had three
      distinct morphologies: (1) vacuolated, tall and columnar cells in the trilaminar
      region; (2) large cuboidal cells in the adjacent bilaminar region; and (3)
      squamous cells in the abembryonic pole of the bilaminar region. These variations
      in cell structure correlate with differences in subsequent functional activity in
      these three regions of the yolk sac placenta.

PMID- 8870101
TI  - Duration of embryonic diapause in the brush-tailed bettong, Bettongia penicillata
      (Potoroidae): effect of age of quiescent corpus luteum.
AB  - It has been shown that changes to the frequency of sucking by the pouch young do
      not affect the time of reactivation of the quiescent corpus luteum and diapause
      embryo in Bettongia penicillata; these observations led to the suggestion that
      the corpus luteum may have an inherent maximum duration of quiescence. The aim of
      the present study was to investigate the effect of the age of the corpus luteum
      on the timing of its reactivation. Ovulation fails to occur post partum in female
      B. penicillata isolated from males, and the introduction of a male B. penicillata
      induces oestrus in females suckling a young in the pouch. Oestrus was induced
      from Day 23 of lactation to Day 76, in different females, and the corpus luteum
      became quiescent. All parturitions occurred between Day 95 and Day 103 of
      lactation (average, Day 98.8), at the time expected if the corpus luteum had been
      formed post partum. Duration of quiescence of the corpus luteum ranged from 60
      days to 10 days, compared with 83.9 +/- 0.43 days in females that mated post
      partum. The results show that the age of the corpus luteum does not affect the
      timing of its redevelopment and release of the embryo from diapause near the end
      of the period of the young being suckled within the pouch.

PMID- 8870102
TI  - The uterine environment in early pregnancy in the tammar wallaby.
AB  - In tammar wallabies, Macropus eugenii, the uterine environment plays a key role
      in regulating development, because during the first two-thirds of gestation an
      acellular mucoid coat and shell prevent direct cell-cell contact between the
      endometrium and embryonic cells. This control is seen very clearly in the
      facultative lactational diapause of tammars. Removal of the suckled pouch young
      during the breeding season terminates diapause, leading to a distinct increase in
      metabolic activity of the embryo. By Day 4, oxidative metabolism of glucose has
      substantially increased, providing a four-fold increase in ATP production. By Day
      5, RNA synthesis has increased. These changes are dependent on progesterone
      induced changes in uterine secretions. By Day 3, there is greater progesterone
      secretion by the corpus luteum and, by Day 4, uterine protein synthesis has
      increased. The nature of the uterine regulatory factor is still not known. There
      are changes in some uterine proteins, but no detectable change in ionic
      components of the uterine fluid. Only one defined potential regulator, platelet
      activating factor, has been identified, the concentration of which increased
      during reactivation. The influence of the steroid hormones progesterone and
      oestradiol on the uterus and diapausing embryo, and other changes that occur
      later in development, are also discussed in the present review.

PMID- 8870103
TI  - Glycosaminoglycans of the uterine and vaginal cul-de-sac tissue in the brushtail
      possum (Trichosurus vulpecula).
AB  - Live-captured feral brushtail possums (Trichosurus vulpecula) received slow
      release progestagen implants for 16 days after removal of pouch young. At the
      time of implant removal one group was injected intramuscularly with pregnant mare
      serum gonadotrophin (PMSG, 2 I.U. kg-1 in 0.2 mL saline) and another group
      received an equivalent volume of sterile saline. Animals from each group were
      killed on Days 0, 3, 4, 5 or 6 after implant removal (PMSG, n = 4 per day; saline
      controls, n = 3 per day). The uterus and vaginal cul-de-sac were excised and
      tissue was analysed for glycosaminoglycans (GAGs) and keratan sulfate content.
      GAG concentration increased progressively over the six-day period following
      implant removal. Mean uterine GAG concentrations were significantly higher than
      those in vaginal cul-de-sac from Day 3 to Day 6 in PMSG-treated and saline
      treated animals following progestagen implant removal (P < 0.05). Keratan sulfate
      concentrations showed a similar response--concentrations were higher in uterine
      tissue than in vaginal cul-de-sac tissue and PMSG-treated animals showed a
      greater response than did saline controls in the uterine tissue, but the same
      response in cul-de-sac tissue (P < 0.05 for all groups). The progressive increase
      in GAG concentrations of reproductive tract tissue following removal of the
      progesterone implant is indicative of hormonal stimulation and suggests that GAGs
      may have a supportive role in gamete and embryo nutrition and growth in the
      brushtail possum.

PMID- 8870104
TI  - Human red cells from prenatal stages of hemopoiesis. Lithium flux components.
AB  - Red cells from umbilical cord with increased lithium content were submitted to
      different experimental conditions in order to study lithium flux components.
      There appeared three components: First, an ouabain-sensitive component, related
      to Na+ replacement with Li+ in the primary active Na+/K+ transport system. The
      magnitude of this fraction is greater than in adults' red cells. Second, an
      outside sodium-dependent Li+ efflux fraction, corresponding to the Li+/Na+
      countertransport system with Vmax and K(m) values of 0.1 (mmol/l cells.h) and
      2.58 (mmol/l), respectively. The Na+o-affinity for lithium efflux in this system
      is greater in neonatal than in adults' red cells. Third, a leak fraction with an
      equal value to that reported in adults' red cells. Furthermore, the possible non
      existence of a bumetanide-sensitive lithium flux fraction was shown in neonatal
      red cells.

PMID- 8870105
TI  - Genetic determination of coat color affects testicular steroidogenesis in the
      Mustela vison.
AB  - Coat color genes in mammals are known to be developmental genes with wide
      pleiotropic effects. The present study was undertaken to study testicular
      steroidogenesis in American Mink (Mustela vison) of various coat color
      phenotypes. No differences in testicular steroid levels were observed between
      fertile and infertile mink with the standard phenotype and genotype (BB jj MM
      PP). Mink with the opaline phenotype and genotype (bb mm pp), were found to have
      in their testes, 20-40% higher levels of progesterone, five times higher levels
      of 17-hydroxyprogesterone, and eight times higher levels of testosterone, than
      the corresponding values in other mink. No other differences were observed among
      the different types of mink. Since the genotype of the opaline mink differs from
      the other mink studied, only in their combination at the pastel (b) and moyle (m)
      loci, their bb mm genotype could be assumed to be responsible for the increase in
      testicular steroids.

PMID- 8870106
TI  - Metabolic effects of the combination of furosemide and captopril in rat.
AB  - Diuretics typically provoke increased serum lipid levels and may provoke
      increased serum uric acid levels and/or glucose intolerance. Furosemide is widely
      used as an antihypertensive, but in patients for whom furosemide treatment alone
      proves insufficient to reduce hypertension, a common procedure is to co
      administer the angiotensin-converting-enzyme (ACE) inhibitor captopril. The
      metabolic effects in rats of joint administration of furosemide (15 mg/kg/day)
      and captopril (2 mg/kg/day) are evaluated over a two-week period. At the end of
      this period, the serum levels of lipids, uric acid, bilirubin, proteins and
      various enzymes were determined as well as the effect of the treatment on
      intestinal absorption of glucose and calcium. Furosemide/captopril led to an
      increase in serum albumin and alkaline phosphatase levels, and a decrease in
      triglyceride levels. The results of this work support the view that this drug
      combination is suitable for hypertension treatment.

PMID- 8870107
TI  - Development of a simple, rapid sandwich enzyme immunoassay for the measurement of
      serum rat LH.
AB  - The present study describes the development and validation of a rapid, sensitive,
      specific and precise enzyme immunoassay (EIA) sandwich suitable for measuring
      luteinizing hormone (LH) in rat serum. Ninety-six well polystyrene microtiter
      plates were coated with 100 microliters (250 ng/ml) of a well-characterized
      monoclonal antibody (518B7, Roser, UC Davis) generated against bovine LH. A
      polyclonal antiserum raised in rabbits against ovine FSH (G4-215B, Papkoff) was
      conjugated to sodium periodate-activated horseradish peroxidase (HRP), and used
      as the second antibody of the sandwich assay. This anti-ovine FSH antiserum cross
      reacted more than 200% with rat LH. Standards (r-LH-RP-3, NIADDK, range 0 pg/well
      to 2.5 ng/well or 100 microliters) diluted in a 3(N-Morpholino) propane sulfonic
      acid (MOPS) buffer, or serum, were incubated with the solid phase antibody for 2
      hours. Plates were washed and the anti-oFSH:HRP (100 microliters) in MOPS buffer
      was added and incubated a further 2 hours before a second wash and the addition
      of the substrate (TMB, 3,3',5,5'-tetramethylbenzidine dihydrochloride and H2O2).
      The least detectable concentration of LH was 16.1 +/- 1.42 pg/ml. The recovery of
      known concentrations of LH added to several samples was 93.5 +/- 1.70%. Mean
      intra-assay and inter-assay coefficients of variation (%) were less than 10% (n =
      20). The anti-FSH:HRP showed less than 8.0% cross reactivity with rFSH in this LH
      EIA system. The correlation coefficient (r) of samples analyzed by EIA in
      parallel with RIA was r = 0.90 (p < 0.001, n = 26). Results showed levels between
      105.21 and 633.87 pg/ml. This new LH EIA sandwich offers a stable, rapid, and
      improved EIA system for the measurement of serum LH concentrations of this
      species over previously reported methods.

PMID- 8870108
TI  - Effect of osmolarity on the epithelial paracellular permeability in rat jejunum.
AB  - Studies in vivo have shown an important increase in the substrate passive
      permeability across small intestine when Na(+)-cotransported substrates, like
      galactose, are present at the luminal side. The influence of the solution
      osmolarity on the passive absorption of mannitol or 2-deoxy-D-glucose across rat
      jejunum and on the galactose-increasing effect is now studied both in vivo and in
      vitro. In vivo, luminal perfusion with 400 or 500 mosm/L solutions does not
      affect passive absorption of 10 mmol/L 2-deoxy-D-glucose, although a net fluid
      secretion towards lumen is observed. Luminal hyperosmolarity, however, prevents
      the stimulatory action of 25 mmol/L galactose on the passive absorption, a
      stimulation that is well manifested in the same intestinal segment when the
      perfusion is made with isoosmotic solutions. However, in vitro results with
      everted intestinal sacs or with preparations of intestinal wall in Ussing
      chambers, indicate that hyperosmolarity (500 mosm/L) of the solutions clearly
      increases net passive mucosal to serosal flux of D-mannitol or 2-deoxyglucose.
      With low osmolarity solutions (180 or 160 mosm/L by diminution of NaCl) the in
      vivo passive mannitol absorption is not affected and the stimulatory action of 25
      mmol/L galactose is not observed, although net water absorption is enhanced.
      Moreover, the passive absorption stimulation by the galactose cotransport in
      isoosmotic solutions is dependent on Na+ levels requiring at least 80 mmol/L.
      Results suggest that passive paracellular absorption across the small intestine
      may be modified by changes in the luminal content composition.

PMID- 8870109
TI  - A potential experimental model for the study of osteopenia in CCl4 liver
      cirrhotic rats.
AB  - In order to search for an experimental model to further investigate the
      osteopenia associated to liver cirrhosis (LC), this study has been focused on
      investigating the occurrence of bone disorders in male rats to which LC
      histologically confirmed was induced through the validated procedure of CCl4
      inhalation. Length, anteroposterior and lateromedial diameters, densitometry,
      mechanical stress resistance, hydroxyproline (OHprol) and calcium and phosphate
      contents were measured in femurs from control (n = 10) and liver cirrhosis rats
      (n = 10). It has been found that femurs from liver cirrhosis rats showed a
      significant reduction (p < 0.01) in bone weight (0.254 +/- 0.003 vs 0.230 +/-
      0.004 g/100 g b.w.), anteroposterior (4.08 +/- 0.06 vs 3.69 +/- 0.05 mm) and
      lateromedial (5.33 +/- 0.05 vs 5.08 +/- 0.04 mm, p < 0.05) diameters, resistance
      to mechanical stress (405.8 +/- 9.5 vs 332.5 +/- 9.1 N) and total densitometry
      (0.416 +/- 0.005 vs 0.381 +/- 0.004 g/cm2). However, no significant differences
      were observed in bone length, calcium, OHprol and phosphate (all expressed as
      mg/100 mg fresh bone tissue) contents. Therefore, the proteins matrix to mineral
      contents ratio was not altered. These results indicate that in this model of
      experimental liver cirrhosis there is osteopenia characterized by bone frailty
      and reduced thickness, and it could offer an experimental model to study bone
      changes associated to liver cirrhosis.

PMID- 8870110
TI  - Role of fragment peptides from ob protein on body weight and thermogenesis
      control: a screening.

PMID- 8870111
TI  - Cyclooxygenase 1 and 2 in rheumatic disease: implications for nonsteroidal anti
      inflammatory drug therapy.
AB  - OBJECTIVES: Prostaglandin synthase (cyclooxygenase) is now known to exist in two
      separate isoforms, termed prostaglandin synthase 1 and 2 (or COX1 and COX2). This
      has prompted a dramatic increase in research regarding the contribution of these
      isoforms to inflammatory disease and their relationship to the efficacy and
      safety of nonsteroidal anti-inflammatory drugs (NSAIDs). The emerging picture is
      that COX1 is responsible for maintaining prostaglandin synthesis in the gastric
      mucosa, platelets, and kidney, whereas COX2 is responsible for prostaglandin
      production in inflamed tissues, including rheumatoid arthritis (RA) synovium.
      This review examines the validity of the hypothesis that NSAIDs exhibiting
      selectivity for COX2 demonstrate an improved safety and efficacy profile when
      compared with NSAIDs exhibiting selectivity for COX1. METHODS: Literature on the
      efficacy and safety (gastric, renal, and hemostatic) of various NSAIDs are
      compared with published data on their relative COX1 and COX2 in vitro
      specificity. RESULTS: No differences in clinical efficacy are evident between
      NSAIDs exhibiting preferential activity for either COX1 or COX2. NSAIDs
      representing the extremes in terms of selectivity for COX1 or COX2 do exhibit
      some differences with respect to gastric, renal, and hemostatic safety; those
      exhibiting a preferential action on COX2 are generally less toxic than those
      exhibiting a preferential activity on COX1. Exceptions do exist. CONCLUSIONS:
      There is some support for the hypothesis that NSAIDs exhibiting a preferential
      action on COX2 are safer than those exhibiting a preferential activity on COX1,
      but there exists no support for improved efficacy. A strict correlation does not
      exist between the COX1 and COX2 specificity and the gastric, renal, and
      hemostatic toxicity of NSAIDs. This lack of correlation is believed to stem from
      the fact that both the safety and efficacy of NSAIDs may result from mechanisms
      distinct from prostaglandin inhibition. Preferential COX2 activity can reduce the
      level of toxicity for a given NSAID but may not be sufficient to overcome
      toxicities resulting from other mechanisms.

PMID- 8870112
TI  - Distinctive features of idiopathic inflammatory myopathies in French Canadians.
AB  - This is the first report on idiopathic inflammatory myopathies (IIM) in French
      Canadians. We reviewed retrospectively 30 French Canadian adults (20 women and 10
      men) with IIM seen consecutively over 12 years. The median age at diagnosis was
      45 years. The IIM were 8 (27%) primary polymyositis (PM), 9 (30%) primary
      dermatomyositis (DM), 5 (17%) IIM with neoplasia (lymphoma, breast, esophageal,
      colonic, and skin cancer) and 8 (27%) IIM with a connective tissue disease (4
      with systemic sclerosis, 2 with mixed connective tissue disease, and 2 with
      rheumatoid arthritis). The most common presenting symptom was proximal muscle
      weakness (n = 10,33%). Of the remaining 20 patients, 6 (20%) had the onset of
      their weakness within 1 month of the presenting symptom. Only 3 (10%) patients
      did not have proximal muscle weakness. Twenty-six (87%) patients had weakness in
      the pelvic girdle, 25 (83%) in the shoulder girdle, and 7 (23%) in the neck
      muscles. Other common symptoms included dyspnea on exertion and dysphagia, each
      present in 13 (43%) patients. Gottron's papules and the heliotrope rash were the
      most common skin lesions documented in 11 (37%) and 10 (33%) patients,
      respectively. The serum creatine kinase (CK) level was between 171 and 1,000 U/L
      in 13 (43%) patients and between 1,001 and 6,000 U/L in 13 (43%) patients.
      Antinuclear antibodies (ANA) on HEp-2 cells were positive in 16 (53%) patients,
      of which 2 (13%) expressed autoantibodies to nuclear pore complexes. Autoantibody
      specificities were anti-La (n = 4, 13%), anti-U1RNP (n = 3, 10%), and anti-Ro (n
      = 2, 7%). None of the patients expressed anti-Jo-1, anti-topoisomerase I, or
      anticentromere antibodies. Twenty-eight (93%) patients received corticosteroid
      therapy, and 8 (27%) patients responded to prednisone alone. Thirteen (43%)
      patients were treated with methotrexate, and 9 (69%) responded. The mean follow
      up was 62 months: 23 (77%) had their disease controlled, 3 (10%) patients were
      lost to follow-up, and 4 (13%) died (no death occurred because of IIM or its
      treatment). Therapy was discontinued because of remission in 5 (17%) patients.
      Cumulative survival rates at 2, 5, and 10 years were 89%, 89%, and 85%,
      respectively. The presence of autoantibodies to nuclear pore complexes and anti
      La autoantibodies, the rare occurrence of anti-Jo-1 autoantibodies, the response
      to conventional therapies, and a high survival rate may distinguish IIM in French
      Canadians from that of other reported series.

PMID- 8870113
TI  - Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases
      in the absence of clinically apparent myositis.
AB  - Autoantibodies against aminoacyl-tRNA synthetases (antisynthetases) have been
      found to be highly specific for polymyositis and dermatomyositis and to correlate
      strongly with complicating interstitial lung disease (ILD). We describe the
      clinical presentations and course of 10 patients with ILD and anti-synthetase
      antibodies in whom underlying myositis was not clinically evident. Anti-PL-12
      antibodies (antialanyl-tRNA synthetase) were most common (60%), followed by anti
      Jo-1 (antihistidyl-tRNA synthetase) and anti-OJ (anti-isoleucyl-tRNA synthetase)
      (20% each). All 10 patients had anticytoplasmic antibodies by indirect
      immunofluorescence on HEp-2 cells. Five of 10 presented with features of
      connective tissue disease, whereas two presented with acute respiratory failure,
      two with insidious onset of diminished exercise tolerance, and one with
      persistent cough. All but one patient received corticosteroids, four were given
      oral cyclophosphamide, and two azathioprine. ILD resolved or stabilized in five
      patients (50%), and progressed in four (40%). The "antisynthetase syndrome" may
      occur in the absence of clinical myositis, and the ILD in these patients is
      usually responsive to therapy. Antisynthetase testing should be considered in
      patients with ILD who have a cytoplasmic pattern by antinuclear antibody (ANA)
      testing on HEp-2 cells, because early recognition and treatment of such patients
      affects their clinical course.

PMID- 8870114
TI  - Outcome of silent lupus nephritis.
AB  - To analyze the long-term outcome in patients with silent lupus nephritis, we
      retrospectively studied 20 patients with systemic lupus erythematosus without
      clinical renal involvement who had renal biopsies in our unit between 1978 and
      1986 and reviewed 193 cases reported between 1957 and 1995. Two patients of the
      current series were lost to follow-up. Mean follow-up in the other 18 was 13 +/-
      3 years (range, 2 to 17). On kidney biopsy, nine had class I, six class II, one
      class IV, and two class V disease (WHO classification). Three patients with prior
      normal renal function died of nonrenal causes. During the study, the remaining 15
      patients had normal renal function and urinalysis. Most patients from the
      literature had "mild" histologic lesions, but 30 had diffuse proliferative
      glomerulonephritis. Over an average of 46 months of follow-up from biopsy, renal
      survival rate and patient survival rate were 98% and 91%, respectively. Three
      patients died of end-stage renal failure. In conclusion, end-stage renal failure
      in patients with silent lupus nephritis is rare regardless of the
      histopathological renal lesions. Patients survival depends on nonrenal causes.

PMID- 8870115
TI  - Necrotizing lymphadenitis associated with systemic lupus erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) may have protean manifestations,
      including necrotizing lymphadenitis. After describing an illustrative case, we
      discuss the incidence, clinical features, and pathologic findings of SLE
      associated necrotizing lymphadenitis. METHODS: A case of SLE associated with
      necrotizing lymphadenitis is reported. The patient's clinical presentation,
      course, and response to therapy is detailed. The literature on lupus
      lymphadenitis is reviewed. RESULTS: A young man who presented with a febrile
      illness characterized by multifocal necrotizing lymphadenitis is described.
      Glomerulonephritis, meningo-encephalitis, pericarditis, and hemolytic anemia
      evolved. The diagnosis of SLE was based on the clinical features, positive
      antinuclear antibody (ANA), and characteristic renal biopsy. High dose
      corticosteroids and cyclophosphamide induced a complete remission. In recent
      series from the literature the prevalence of lymphadenopathy was 12% to 59% of
      patients with SLE. The most common nodal groups involved were cervical (43%),
      mesenteric (21%), axillary (18%), and inguinal (17%). Lymph node pathology was
      characterized by paracortical foci of necrosis and infiltration by histiocytes,
      lymphocytes, plasma cells, and immunoblasts. The hematoxylin body, an amorphic
      aggregate of basophilic material, was pathognomonic of lupus lymphadenitis. The
      necrotizing lymphadenitis of SLE is pathologically similar to Kikuchi-Fujumoto
      disease (KFD), a distinctive, self-limited form of necrotizing lymphadenitis. The
      pathologic and clinical literature support a close link between SLE and KFD.
      CONCLUSIONS: SLE can be complicated by necrotizing lymphadenitis, with
      distinctive pathologic features. Lupus lymphadenitis and KFD share some common
      clinical and pathologic features, supporting a relationship between the
      disorders.

PMID- 8870116
TI  - Health-related quality of life after total hip replacement.
AB  - Total hip replacement (THR) is a commonly performed orthopedic procedure with an
      increasing rate of utilization. It is performed to relieve symptoms of pain and
      help restore the loss of function that follows advanced hip diseases, including
      osteoarthritis, rheumatoid arthritis, and avascular necrosis. Although there are
      numerous studies evaluating patient outcomes after THR with respect to physical
      functioning and pain relief, relatively few studies have specifically evaluated
      changes in health-related quality of life (QOL). We reviewed a total of 20
      studies that evaluated changes in QOL after THR. Results of all studies were
      consistent in showing beneficial and often dramatic improvements in QOL after
      elective THR. These improvements were most likely to occur within the first 3 to
      6 months after THR. Future research should assess the impact of both patient
      level predictors and the role of various surgical approaches in contributing to
      successful outcomes after THR.

PMID- 8870117
TI  - Antioxidant effects of hyaluronan and its alpha-methyl-prednisolone derivative in
      chondrocyte and cartilage cultures.
AB  - OBJECTIVE: To compare hyaluronan and its alpha-methyl prednisolone derivative
      (HYC-141) with respect to their potential to directly cause tissue damage and to
      protect tissues from attack by reactive oxygen species. METHODS: Cartilage
      samples and chondrocytes were isolated from 15-day chick embryos and were exposed
      to enzyme-based and activated inflammatory cell-free radical generating systems
      in the presence of varying concentrations of alpha-methyl prednisolone,
      hyaluronan, and HYC-141. Tissue and cell vitality was measured by determining the
      incorporation of radioactive sulphate into newly synthesized glycosaminoglycans.
      RESULTS: Only alpha-methyl prednisolone caused a significant decrease in
      biosynthetic activity. All the tested substances were capable, to some extent, of
      protecting tissues and cells from damage by reactive oxygen species; HYC-141
      demonstrated the greatest protective effect. CONCLUSION: These data suggest that
      HYC-141 may possess certain advantages over the individual component molecules in
      the local treatment of arthropathies.

PMID- 8870118
TI  - Adrenal insufficiency in the antiphospholipid-antibody syndrome.

PMID- 8870119
TI  - Regulation of cerebrovascular prostaglandin E2 (PGE2) and PGF2 alpha receptors
      and their functions during development.
AB  - The density of PGF2 alpha (FP) and PGE2 (EP) receptors on the cerebral
      microvasculature of the newborn is less than on that of the adult animal. High
      levels of prostaglandins in the newborn brain could be responsible for down
      regulation of FP and EP receptors and their functions in the cerebral
      microvasculature. Cerebrovascular FP and EP receptor density, receptor-coupled
      second messenger production and cerebral vasoconstrictor responses to PGF2 alpha
      and PGE2 were studied in newborn pigs (1 to 2 days old) treated intravenously
      with ibuprofen (40 mg/kg every 6 hours for 48 hours) or saline, and compared with
      adults. Ibuprofen treatment in the newborn increased brain microvascular FP and
      EP receptor densities to levels found in that of adult pigs. Likewise brain
      microvessel inositol 1,4,5-triphosphate production in response to PGF2 alpha,
      fenprostalene (PGF2 alpha analog), PGE2, 17-phenyl trinor PGE2 (EP1 receptor
      subtype agonist) and M&B 28,767 (EP3 agonist) was greater in ibuprofen-treated
      newborn pigs; the latter was associated with increased vasoconstriction to these
      agents to levels comparable with those of adults. Steady-state levels of FP
      receptor mRNA in cerebral microvas-culature did not differ between saline-treated
      newborn, and ibuprofen-treated newborn and adult pigs. It is concluded that the
      low FP and EP receptor densities and receptor-coupled functions on newborn brain
      microvessels seem to be secondary to high levels of brain prostaglandins; the
      changes in receptor levels do not seem to be related to steady-state levels of
      receptor mRNA in brain microvessels.

PMID- 8870120
TI  - Nitric oxide and lung surfactant.
AB  - Inhalation of nitric oxide (NO) is an experimental treatment for severe pulmonary
      hypertension. Being rapidly metabolized by hemoglobin, inhaled NO causes
      selective vasodilation in the pulmonary vascular bed. In addition to the vascular
      smooth muscle, other pulmonary structures are exposed to inhaled NO, resulting in
      suppression of NO synthesis in a variety of pulmonary cells and in potential
      toxicity. NO is a free radical that interacts with a number of proteins,
      particularly metalloproteins. Together with superoxide radical, it rapidly forms
      highly toxic peroxynitrite. Peroxynitrite is involved in the killing of microbes
      by activated phagocytosing macrophages. In severe inflammation, peroxynitrite may
      be responsible for damaging proteins, lipids, and DNA. Peroxynitrite added to
      surfactant in vitro is capable of decreasing the surface activity, inducing lipid
      peroxidation, decreasing the function of surfactant proteins, SP-A and SP-B, and
      inducing protein-associated nitro-tyrosine. Exposure of animals for prolonged
      periods (48 to 72 hours) to inhaled NO (80 to 120 ppm) has been associated with a
      decrease in surface activity. This is caused by binding of surfactant to iron
      proteins that are modified by NO (particularly methemoglobin), or by
      peroxynitrite induced damage of surfactant. In contrast, exposure of isolated
      surfactant complex to NO during surface cycling strikingly decreases the
      inactivation of surfactant, preventing the conversion of surfactant to small
      vesicles that are no longer surface-active, and preventing lipid peroxidation.
      This finding is consistent with the function of NO as a lipid-soluble chain
      braking antioxidant. It is possible that this lipophilic gas has as yet undefined
      roles in regulation of surfactant metabolism and maintenance of surface activity.
      Deficiency in pulmonary NO may be present during the early neonatal period in
      respiratory distress syndrome and in persistent fetal circulation. The premature
      lung is likely to be sensitive to NO toxicity that may include lung damage,
      abnormal alveolarization, and mutagenicity. Defining of the indications, the
      dosage, and the toxicity of inhaled NO therapy remains the challenge for
      experimental and clinical research.

PMID- 8870121
TI  - Effect of modulators of hypoxic pulmonary vasoconstriction on the response to
      inhaled nitric oxide in a neonatal model of severe pulmonary atelectasis.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is an intrinsic mechanism that
      facilitates ventilation to perfusion matching and preservation of oxygenation. We
      investigated the neonatal HPV response from extensive atelectasis and tested the
      hypothesis that (I) the resulting hypoxemia is corrected by inhaled nitric oxide
      (NO); (2) the "pulmonary steal" of blood away from hypoxic area is further
      improved by modulators of the HPV. Intratracheal injection of steel beads in 32
      piglets (7 to 20 days) resulted in atelectasis of 50% to 75% of the lungs. The
      piglets were then randomized to receive saline (control), indomethacin (IND) 2
      mg/kg, doxapram (DOX) 0.5 mg/kg/h or almitrine (ALM) 4 micrograms/kg/min. After
      30 minutes, all animals were subjected to NO at 40 ppm. Atelectasis resulted in
      severe impairment in oxygenation (PaO2 - 105 +/- 6 mm Hg, AaDO2 = 536 +/- 9 mm
      Hg; shunt fraction = 31% +/- 2%) and moderate pulmonary hypertension. Mean
      pulmonary artery pressure (PAP) increased to 35 +/- 0.8 mm Hg. NO reduced
      pulmonary vascular resistance (PVR) from 128 +/- 14 mm Hg/kg/mL/min to 74 +/- 9
      mm Hg/kg/mL/min and improved gas exchange (PaO2 = 180 +/- 50 and AaDO2 = 438 +/-
      50 mm Hg). Following the development of atelectasis, the peripheral chemoreceptor
      agonists (ALM and DOX) did not modify gas exchange and had no significant
      cardiovascular effect. ALM and DOX failed to enhance the response to NO. IND did
      not alter HPV, but prevented the improvement in gas exchange associated with NO
      induced pulmonary vasodilation.

PMID- 8870122
TI  - Cytokines and production of surfactant components.
AB  - The production of pulmonary surfactant, a complex of lipids and proteins that
      reduces surface tension at the alveolar air-liquid interface, is developmentally
      regulated. Several hormones, most notably glucocorticoids, are known to
      accelerate maturation of the surfactant system. Cytokines are polypeptides that
      act mostly in a paracrine fashion and possess a wide spectrum of activities on
      multiple types of cells. Many cytokines are produced by different lung cells a
      various stages of fetal development or under pathological conditions affecting
      the fetus. In addition, cytokines present in amniotic fluid or in the blood
      stream may reach the fetal lungs. Some cytokines, including epidermal growth
      factor, transforming growth factor-alpha, and interferon-gamma have been shown to
      stimulate the production of surfactant components. On the other hand, tumor
      necrosis factor and transforming growth factor-beta downregulate the production
      of surfactant lipids and proteins. We have recently shown that the
      proinflammatory cytokine interleukin-1 (IL-I) enhances the expression of
      surfactant protein A (SP-A) in fetal rabbit lung explants. In addition, injection
      of IL-I into the amniotic fluid of fetal rabbits enhances the expression of
      surfactant proteins and improves the lung compliance of preterm animals. Preterm
      delivery is often associated with subclinical intraamniotic infection. In these
      cases, amniotic fluid concentrations of IL-I are often elevated. We propose that
      this cytokine accelerates maturation of the surfactant system in fetal lungs and
      thus prepares the fetus for extrauterine life.

PMID- 8870123
TI  - Evidence from twin study implies possible genetic susceptibility to
      bronchopulmonary dysplasia.
AB  - To investigate the possibility that susceptibility to bronchopulmonary dysplasia
      (BPD) is affected by genetic factors, we analyzed risk factors for BPD in 108
      twin pairs of infants having birth weight < or = 1,500 g. When BPD occurred in a
      first born twin (n = 23), it also occurred in 65% (n = 15) of the second born
      twins, and when BPD did not occur in the first twin (n = 85), it only occurred in
      8% (n = 7) of the second twins (crude odds ratio = 20.9). After adjusting for
      potentially significant risk factors including birth weight, gestational age,
      gender, diagnosis of hyaline membrane disease, pneumothorax, symptomatic patent
      ductus arteriosus, and year of admission, using multiple logistic regression on
      the entire database (1,872 admissions < or = 1,500 g), BPD status of a first twin
      remained a highly significant predictor of BPD in the second twin (adjusted odds
      ratio = 12.3, P < .001). Other factors including birth order of twins, twin
      gestation, inborn/outborn status, cesarean section delivery, 1- and 5-minute
      Apgar scores, maternal race, maternal diabetes, and antepartum corticosteroid
      treatment were not significant predictors of BPD. These results are consistent
      with genetic factors affecting the susceptibility of very low birth weight
      premature infants to BPD, but we cannot exclude the possibility that factors not
      included in our analysis are also involved.

PMID- 8870124
TI  - Beyond the orthodox: heresy in medicine and the social sciences from a cross
      cultural perspective.
AB  - An analysis of the concepts of orthodoxy and heresy with due consideration to the
      social context (historical, religious, cross-cultural dimensions), within which
      the terms are discussed, leads us to look historically at its European
      significance embodied in the witch-craze of the 15th-17th centuries. One way to
      conceptualize heresy is to analyze it in the context of the relationship of the
      scientists and scientific theories vis-a-vis societal establishment (ie. power
      bases such as governments, finance bases, public consensus). Today, unorthodoxy
      lies in attempts to accomplish interdisciplinary work, or in proposing
      alternative explanatory strategies (as in alternative medicine). A shift in
      scientific paradigms seems to characterize the revolutionary changes of our era.
      The foremost challenge in the construction of new paradigms seems to be the
      ability to effectively integrate the components of emotion or feelings taking
      into account both those of the researcher as well as those who are being
      investigated. This will involve a new conceptualization of objectivity. In an era
      which is distinguished by globalization, such a task necessitates a new level of
      understanding that integrates gender related analysis as well as the implications
      of the recognition of cross-cultural interaction and cultural diversity.

PMID- 8870125
TI  - Medical heresy--the view of a heretic.
AB  - The failures of Modernity and qualities of its heresy have opened space for
      heresy in medicine. One form of medical heresy is alternative medicine. The basic
      features of alternative medicine cannot fit into Cartesian norms of orthodox
      medicine. They can be explained by the principles of a holographic paradigm.
      Alternative medical narrative, like general heresy, offers hope in a world where
      hope is withering away.

PMID- 8870126
TI  - Causes of change in the health of populations: a biopsychosocial viewpoint.
AB  - In the current review, a biopsychosocial perspective is applied to current
      changes in the health of populations. It is proposed that the psychosocial
      environments either promote health or precipitate disease. Changes in the types
      of stress that people experience as well as its prevalence over time are
      discussed. In addition, possible biological mechanisms linking the psychosocial
      environments to health are presented. "Food for thought" is the possible
      interaction between the physical/chemical and the psychosocial environments and
      changes in health of individuals. Clearly, our traditional view of disease
      mechanisms is not sufficient to understand recent phenomena, such as
      environmental illness and chronic fatigue syndrome. Issues worthy of further
      discussions are the role of the "just-in-time" society, where individuals
      increasingly have to change jobs, cope with reorganizations and increased
      production pressure, and its impact on health and well-being. Further, in what
      way can we develop better models to truly assess the impact of an increasingly
      complex interaction between individual and environmental factors on health? A
      major obstacle to enhancing our understanding of causes of change in the health
      of populations is the use of inappropriate or outdated statistical analytical
      models. Finally, it is suggested that prospectively controlled studies of the
      impact on health of changes in the health and welfare systems are carried out.
      This would further add to our understanding of factors contributing to changes in
      the health of population.

PMID- 8870127
TI  - Child survival: physical vulnerability and resilience in adversity in the
      European past and the contemporary Third World.
AB  - Infant and child physical vulnerability is demonstrated by the extremely high
      mortality levels in these age groups in the pre-modern West and parts of the
      contemporary Third World. Some children, such as females or later additions to
      the family, are subject to disproportionately high mortality risk. In spite of
      the age-old vulnerability of young children, disproportionate gains have been
      made in reducing their mortality in modern times. This has been a product of
      social and individual change, government intervention and biomedical research.
      These advances exhibit during crises greater resilience to reversal than might be
      anticipated. Rarely do infant and child mortality levels return more than a
      fraction of the way to the original levels. The explanation is irreversible
      changes to individuals and society and the persistence of health knowledge even
      when health facilities are paralysed.

PMID- 8870128
TI  - Child development: vulnerability and resilience.
AB  - Many of the challenges facing children now are a function of changing times,
      including increase in urbanization, political violence, changing family forms,
      and in some areas decreased supplies of adequate food. This review focuses
      particularly on those changes in which children are the victims and which induce
      new threats for them, rather than on problems such as child disability or mental
      illness. The outcome variables of interest in this paper are dimensions of
      children's psychosocial development, including cognitive development,
      psychological adjustment and aggression, whereas the companion paper in this
      issue (Caldwell P., Child survival: vulnerability and resilience in adversity in
      the European past and the contemporary Third World, Soc. Sci. Med.) [1] focuses
      on physical aspects of children's development. The risks that are hurdles in the
      process of development of a young child begin from conception and carry on into
      later life. To address them all would be impossible; thus, in order to do justice
      to the issues at hand, we have chosen those risks that, in our view, are
      important in a child's psychosocial development in developing countries. This
      paper will thus provide a discussion of the concepts of risk and resilience, then
      apply these concepts to the analysis of three examples of risk faced by children
      today: nutritional threats (e.g. malnutrition due to decline in breastfeeding);
      family dynamics and types of family forms (e.g. child fostering and non
      traditional families); and experiences of violence (domestic or political). In
      each case, the same four questions will be addressed: what are the consequences
      of the risk factor for children, what are the etiologies and conditions of risk,
      are there any children who seem to cope with the risk factor successfully and
      what are some of the protective factors, and what interventions or programs would
      help support these children?

PMID- 8870129
TI  - Health system reforms--toward a framework for international comparisons.
AB  - Health care reform efforts internationally are focused more on efficiency than on
      effectiveness or equity. We lack a coherent theoretical framework for
      understanding those reforms or for engaging in comparative research. This paper
      presents some theoretical ideas that could contribute to such a framework. A
      model constructed from expert opinion suggests that hegemonic systems, national
      systems and medical care systems all contribute, with specific elements
      identified in each. Three sociological ideas are suggested: a model of trends
      leading to a fiscal crisis and a crisis of alienation; communities, professions
      and markets as ideal typical organizational alternatives; global post-Fordist and
      world systems theories; and hegemonic projects. Together these could explain the
      timing, speed and direction of health care reform efforts throughout the world.

PMID- 8870130
TI  - Market-oriented health care reforms: trends and future options.
AB  - In many (predominantly) publicly financed health care systems market-oriented
      health care reforms are being implemented or have been proposed. The purpose of
      these reforms is to make resource allocation in health care more efficient, more
      innovative and more responsive to consumers preferences while maintaining equity.
      At the same time, the advances in technology result in a divergence of consumers'
      preferences with respect to health care and urge society to (re)think about the
      meaning of the solidarity principle in health care. In this paper we indicate
      some international trends in health care reforms and explore some potential
      future options. From an international perspective we can observe a trend towards
      universal mandatory health insurance, contracts between third-party purchasers
      and the providers of care, competition among providers of care and a
      strengthening of primary care. These trends can be expected to continue. A more
      controversial issue is whether there should also be competition among the third
      party purchasers and whether in the long run there will occur a convergence
      towards some "ideal" model. Although regulated competition in health care can be
      expected to yield more value for money, it might yield both more efficiency and
      higher total costs. It has been argued that equity can be maintained in a
      competitive health care system if we interpret equity as "equal access to cost
      effective care within a reasonable period of time". Because the effectiveness of
      care has to be considered in relation to the medical indication and the condition
      of the patient, the responsibility for cost-effective care rests primarily with
      the providers of care. Guidelines and protocols should be developed by the
      profession and sustained by financial incentives embedded in contracts. It has
      been argued that the third-party purchasers could start to concentrate on the
      contracts with the primary care physicians. Contracts with other providers could
      then be a natural complement to these contracts. Coordinated-care contracts
      between the third-party purchasers and the consumer of care could provide the
      consumer with monetary incentives to go to efficient providers. A consumer choice
      of insurance contract could give the consumer an opportunity to make important
      choices in health care. However, each society has to make its own choices about
      what care should be available to everybody independent of an individual's
      purchasing power.

PMID- 8870131
TI  - Cultural problems of ageing especially regarding gender and intergenerational
      equity.
AB  - The absence of old age as a specific social group in some cultures raises the
      question of ageing as a cultural construction. In this paper we will consider
      only problems of cultural ageing in industrial Western society and especially in
      some OECD countries. There, demographic changes have been characterised by ageing
      of populations, visible since the fifties, by feminization of later life and
      modifications of social network. Ageing of population including the oldest
      generations have made definitions of later life more politicized and have gone
      together with new attitudes towards ageing and elderly people giving rise to
      different patterns of ageism. Examination of incomes, health status, social
      support of the elderly shows that until today there have been persistent
      inequalities related to age, gender and social class in terms of resources,
      access to informal and formal care and value accorded to later life. These
      inequalities are due to differences in status and resources of elderly and
      trajectories of ageing, always conditioned by social locations: position in
      labour market and in domestic division of labour with resulting social relations.
      The differences vary also between countries according to their welfare regime and
      their social policy. In the future, the proportion of those over 65 of age and
      among them of those ever 80 will be greater raises the questions of health status
      of the oldest generations, income distribution among generations and genders, of
      access to informal and formal care and adequacy of the later for the frail
      elderly. To cope with those issues ageing and later life should be considered in
      a life-span perspective. Better sharing of jobs and of economic wealth,
      development of meaningful activities other than work may be solutions to answer
      to the questions addressed by an ageing population and the problems of later
      life.

PMID- 8870132
TI  - Cultural aspects of ageing: gender and inter-generational issues.
AB  - A broad review is made of the economic, social and political developments that
      accompanied the 20th century demographic transition in the developed
      industrialized societies of Europe and North America and their implications for
      older people, emphasizing changes in work patterns, the position of women, family
      and household structures. The denigration of older people is not new, but there
      is greater consciousness of the disadvantaging aspects of ageist expressions. The
      different stages of economic development and family systems and norms in
      developing societies now undergoing the demographic transition in Asia and
      elsewhere are likely to make the lives of older people there very different from
      those experienced during the transition period in Europe.

PMID- 8870133
TI  - Obstacles to community health promotion.
AB  - The health transition ushered into the world in this century calls for a
      reorientation of traditional health services to manage the new causes of
      morbidity and mortality, renewing interest in disease prevention and health
      promotion. Community-based health promotion emphasizes prevention and community
      participation with people's empowerment to overturn current inequities and
      increase control over their health. Encouraged worldwide by the World Health
      Organization for the last two decades, some community health promotion programs
      have been implemented and lessons learned. However, the shift in focus required
      means nothing less than a paradigm change demanding not only a reorientation of
      professional training, but also a reorganization of social structures in
      communities. This article discusses nine of the interrelated obstacles that must
      be overcome to further develop community health promotion.

PMID- 8870134
TI  - Empowering patients: issues and strategies.
AB  - Over the past few decades perspectives derived from critical social theory and
      other critical perspectives have infused the discourse on health, illness and
      healing, and have heightened awareness of the ways in which social and economic
      inequities experienced by particular groups determine their health. The influence
      of these paradigms in the health sciences occurs, simultaneously, with other
      movements in health care services and delivery. There has been major overhauling
      of health care delivery systems in many western nations with concomitant call for
      greater public participation and individual responsibility for health and health
      care (self-care). As these movements have gained momentum, ideas that suggest how
      people will be enabled both to attain greater social equality and to take
      increased responsibility for their health have flourished, and patient/consumer
      empowerment has become a central concept in the discourse on health. Drawing on
      research data from multiple sources I begin to interrogate what the notion of
      empowerment might mean for patients living with a chronic illness, particularly
      women who have immigrated to Canada; I examine the multiple layers of contexts
      that organize their experiences of illness. Building on earlier research that
      explicated the unstated ideologies that underpin the self-care movement. I extend
      this analysis to examine the conceptual underpinnings of "empowerment". While not
      dismissing the idea of "consumer empowerment" I question whether unreflexive use
      of this notion within the "health care industry" might deflect our attention from
      the structures that perpetuate social inequities. I conclude by arguing for a
      perspective that will allow us to address issues pertaining to the notion of
      empowerment in the lives of patients, generally, as well as those who are
      marginalized and disadvantaged.

PMID- 8870135
TI  - Gender perspectives and quality of care: towards appropriate and adequate health
      care for women.
AB  - Gender inequalities in health are a consequence of the basic inequality between
      men and women in many societies. Despite the importance of socio-economic
      factors, women's health is also greatly affected by the extent and quality of
      health services available to them. Both non-governmental women's organizations
      and feminist health researchers have in recent years identified major gender
      inequalities in access to services and in the way men and women are treated by
      the health care system. Firstly, although women are major health care users as
      well as providers, they are under-represented in decision-making in health care.
      Secondly, no justice is done in general to existing differences in position and
      needs of women and men in defining quality of health care, i.e. gender aspects.
      Among women's organizations, there is general agreement that "gender sensitive
      health care should be available, accessible, affordable, appropriate and
      acceptable". In addition, health care for women should be adequate and not depart
      from a male model of health and illness. In this paper, we pay attention to
      inappropriate health care for women on the one hand, as illustrated by the
      increasing medicalization of women's reproductive life [menstruation, menopause,
      pregnancy and childbirth and (in)fertility]. On the other hand, we discuss gender
      bias in the management of serious, life-threatening diseases such as
      cardiovascular disease, lung cancer, and kidney failure, as a form of inadequate
      care. These examples are followed by a global vision on quality of care from a
      gender perspective, as formulated by the women's health care movement in the
      Netherlands and at the Fourth International Conference on Women in Beijing. If
      anything, the recommendations agreed upon in Beijing will have to ensure the
      consolidation and enhancement of good quality health care for women around the
      world. The final discussion, attempts to give some general recommendations for
      achieving more adequate (gender sensitive) and appropriate (non-medicalizing)
      health care for women. These recommendations pertain to health and health care
      research, policy, education, and organization from a women's perspective.

PMID- 8870136
TI  - Gender perspectives and quality of care in underdeveloped countries: disease,
      gender and contextuality.
AB  - There is indisputable evidence that health indices for women are far worse than
      those for men, yet women have limited access to health resources. Numerous
      reasons have been cited for the poor health of women, and include legal
      constraints to owning property, the lack of participation in the planning
      process, preferential treatment for boys, and social values, norms and customs.
      Most of the research on women while adequately documenting these facts, fails to
      contextualize them in a social, economic and political setting which is often
      responsible for the problems in the first place. This serious shortcoming negates
      the efficacy of the well-intentioned and well-meaning solutions in redressing the
      gender balance. Unless one examines the structural factors which actually cause
      disease, both in men and women in underdeveloped countries, solutions will be
      ineffective. The paper also highlights the important fact that there are many
      more similarities between men and women of the same social class than is
      appreciated, similarities which are possibly greater than those between the same
      gender across different social classes.

PMID- 8870137
TI  - Policy issues in the private health sector: examples from long-term care in the
      U.K.
AB  - The international trend towards private markets in health care can be illustrated
      very clearly by developments over the last decade in the U.K., where the balance
      of health care provision has shifted from a predominantly free, public and
      comprehensive system to more of a mixed economy model. The shift can be
      attributed to a variety of factors, and not government policy alone. The
      relationship between the private and NHS sectors of health care is not a simple
      one and there are both positive and negative implications of the public-private
      mix. The growth of private hospitals and acute beds has dominated debates about
      private health care, but further policy issues have emerged in relation to the
      significant growth in private residential and nursing home care. This paper
      briefly reviews developments in private health care and then explores the key
      policy issues associated with this development. Secondly, an analysis of
      developments in the private residential care sector is undertaken highlighting
      the relationship between the public and private sectors of care provision. Policy
      issues pertaining to the long-term care sector of private health care are raised,
      including the regulation of residential care, regulatory models, enforcement and
      quality, and standards of care. Lessons for the regulation of private health care
      generally are considered and the implications for the private sector of a growing
      trend towards market deregulation are explored. Future models of long-term care
      are discussed and the likely balance between the public and private sectors
      explored.

PMID- 8870138
TI  - Pooling public and private funds in the patient's interest: the case for long
      term care insurance.
AB  - Although the extent of medical care in France may be thought adequate, the same
      does not apply to the social medicine sector. The Assurance-maladie paid 87.7% of
      hospital health expenditure in 1994, whereas direct funding of home assistance
      amounted to only 9%. In contrast, a recent Legos study (Bungener M. et al. Le
      bilan economique et financier du secteur medico social, Universite de Paris IX,
      Legos, Janvier 1994) [1] estimated that home assistance costs represent 41-50% of
      medical-social expenditure. When people are unable to manage because of the high
      costs of their invalidity, the social security system comes to their assistance,
      although only under Draconian conditions involving compulsory "family support
      commitments" and the state's claim on the inheritance of the beneficiary (total
      costs for hospital admission and boarding and the dual limits of 1000F
      liabilities and 250,000F net assets for home assistance). The elderly well
      appreciate the severity of this problem and are deeply distressed by the thought
      of dependency. Many, however, live under the illusion that the social security
      system or, to a lesser extent, the mutual funds will come to their assistance,
      although the problems involved lie partly outside their remits. We therefore need
      to design new systems to allow the elderly to finance their costs should they
      become dependant.

PMID- 8870139
TI  - Disease ecology at a crossroads: man-made environments, human rights and
      perpetual development utopias.
AB  - There is a growing body of critical literature on health, development and
      environmental sustainability in a world of finite resources and overburdened
      ecosystems. The ethics of progress and perpetual development in pursuit of
      unlimited economic growth and ever-expanding markets are no longer viable, given
      the constraints imposed on the life-support systems of the biosphere and a finite
      resource base, which poses the most serious threat to life on Earth. Despite
      increasing evidence of the linkages between economic growth and environmental
      deterioration and a rhetoric expressed in a growing body of laws, regulations,
      accords and global "agendas" at the national and international level, there are
      all too few success stories in reversing or even slowing down the current trends
      of ecosystem degradation and decreasing cultural and biological diversity. On the
      contrary, there is evidence that environmental stress and deterioration are
      increasing, and the impact on the mental, physical and social health and well
      being of populations is more significant now than in any previous time in
      history. The fragmentation of countries, the rise of nationalism and ethnic
      conflict, the decimation of indigenous nations and human rights abuses are often
      closely interrelated with environmental degradation and development initiatives.
      This paper reviews some of the concepts and underlying values of the main
      "models" developed by health and social scientists for interpreting this reality,
      with the aim of stimulating debate that could lead to the adoption of a larger
      and more comprehensive framework for analysing the interactions between human
      health, development and environmental change.

PMID- 8870140
TI  - Public health care provisions: access and equity.
AB  - Within the current exercise of reforming the health care system, underlying all
      issues, is the reassessment of the role of government. It is a government's
      responsibility and concern that the health sector be accessible and equitable to
      the population, and more important that the health sector be more efficient and
      affordable. Many governments in the world attempt to provide universal health
      care services to their population through public health care provisions. This
      paper reviews and analyses the experience of the Malaysian health system,
      focusing on the performance of the system in relation to access and equity. The
      performance of the Malaysian health system has been impressive. At minimum cost
      it has achieved virtually accessible and equitable health care to the entire
      population. This is evident by analysing almost all the commonly used indicators.
      These clearly show that when matched to comparable countries, health outcome is
      even better than predicted value.

PMID- 8870141
TI  - Responses of mental health professionals to man-made trauma: the Israeli
      experience.
AB  - The reactions and responses of mental health professionals in the area of armed
      conflict is the focus of this paper. It examines the way the therapeutic
      community has dealt with the survivors of two catastrophes-the Holocaust and
      warfare. A parallel process of a gradual change of attitudes towards the
      survivors was observed: emotional detachment, lack of recognition in the early
      stages and, eventually, social acceptance and empathy. The origins of these
      attitudes will be discussed, and three explanations will be offered. Israel is a
      small, stress-ridden country that has known seven full-scale wars and countless
      hostilities during its 47 years of existence. Our national history over 2000
      years has been beset with persecution, programs and deportations, culminating in
      the Nazi Holocaust. The establishment of the State of Israel brought with it the
      hope of a secure existence. Unfortunately, this has not been achieved, and Israel
      is a natural laboratory of war stress. The reactions and responses of mental
      health professionals in areas of armed conflict is the focus of this paper.
      Presented here will be this author's analysis of the way the Israeli society and
      the helping professions in Israel have dealt with two kinds of man-made
      catastrophic events: the Nazi Holocaust and seven Arab-Israeli wars. In these
      different events of human violence, a parallel process of a gradual change of
      attitude towards the survivors was observed. This remarkable parallel presents
      emotional detachment, lack of recognition and at times blaming the victims in the
      early stages and, eventually, social acceptance and empathy. The process of
      social change becomes complex when the agents of change are themselves members of
      the social entity undergoing the change. This paper shall demonstrate that
      therapists and mental health planners had considerable difficulties in
      transcending public attitudes toward survivors of the Holocaust and psychiatric
      casualties of the Israeli-Arab conflict. As a result, they were unable to treat
      properly those injured by trauma until certain social changes took place. This
      paper submits that the Israeli experience is not isolated and limited to our part
      of the globe. It represents a general, universal process, from which parallel
      processes in other countries and in other man-made trauma can be drawn.

PMID- 8870142
TI  - Responsibilities and rights in the promotion of health: differing positions of
      the individual and the state.
AB  - Medicine is the practice of humanitarianism. Its purpose should be to help others
      with benevolence and love. One must not think of one's own interest but should
      save and help the people who were created by Heaven and Earth (Veatch R. M. A.
      Theory of Medical Ethics, New York: Basic Books, 1981) [1].

PMID- 8870143
TI  - Health care: a social contract in transition.
AB  - Health care reform around the world is born in considerable measure of the need
      to reconcile our growing capacity to provide effective health care with
      diminishing economic means to sustain this capacity indefinitely. It is precisely
      under these circumstances that the conflict between individual rights to health
      care and the state's responsibilities to provide it becomes unavoidable. Although
      it cannot be eliminated, the conflict can be managed. But the task requires us to
      go beyond formulating economic policies or designing new structural systems for
      delivering health care. It requires an understanding of the purpose of health
      care for individuals and society. It includes stipulating limitations for
      individual rights and state responsibilities. Because of these limitations, the
      task must be guided by the requirements of justice. Health care as both a private
      and common good is at the center of a distributive struggle. At one level the
      focus of this struggle is economic and political. At another level it is moral
      and revolves around the concept of health itself, considered in its biological,
      psychological and social dimensions. Here the issue becomes health as a right,
      together with the implications such a right has for our efforts to balance the
      freedom of individual health-related behavior with the interests of the public's
      health. What, in that balance, are the rights of the individual and the
      responsibilities of the state? Can the individual citizen hold the state
      accountable for securing the conditions necessary for health? Can the state hold
      its citizens accountable for irresponsible health-related behavior? A discussion
      of providing liver transplantation sheds considerable light on these questions,
      while suggesting a paradigm for use with general health care services. Central to
      this paradigm is the welfare concept of right, balanced by the understanding that
      a citizen's claim on health care services is limited. In the final analysis,
      justice in health care will be achieved through a division of labor, at the
      center of which there is a set of reasonable and binding expectations shared
      reciprocally between the individual and the state.

PMID- 8870144
TI  - Health care reform and the labor market.
AB  - Reform is probably the most frequently used term when discussing health care
      systems. The literature is broad and general, with topics ranging from reasons
      for carrying out reform, through discussion and the meaning of the reform, to
      discussions of methods for reform in developing countries. Interest has been
      centered more on the definition of content and less on the processes of
      implementation. Implications in terms of changes in the requirements of health
      facilities and human resources have been only superficially addressed. This paper
      presents a conceptual framework to discuss the main issues involved in reform of
      the health care systems and the shifts in needs of human resources. Assessment of
      the ways in which reform affects the medical labor market require the application
      of a conceptual framework that enables us to focus more on process than content.
      In the organizational change literature, both in theory and practice, human
      resources have been found critical for the institutionalization of organizational
      change. They are also critical for assessing health care reform.

PMID- 8870145
TI  - The changing roles of health care personnel in health and health care management.
AB  - Health care reform has become a global phenomenon. Countries are experiencing
      similar problems with their health care systems and are reaching for similar
      solutions. Management is seen as crucial in many countries as the principal means
      of securing supply-side reforms. Many of these centre on establishing a new
      relationship between professionals, notably the medical profession, and the
      state. The aim has been to exercise greater influence over how professionals
      practice and use resources. The application of new public management principles
      based on industrial sector practices and concepts of management has created
      tensions within professional groups who feel themselves, and their craft, to be
      under attack. But the new managerialism has to be seen within a context of rapid
      social and economic change. It is not possible to predict what the impact of such
      change is likely to be on health services in the future or on those who provide
      them. The paper offers an overview of health care reforms and assesses how it is
      shaping, or re-shaping, the roles and tasks of health care personnel. One
      conclusion is the mismatch between the management style favoured by policy-makers
      and reformers and the necessary flexibility required in skill mix and
      organization of work. High-trust relations lie at the heart of professional forms
      of organisation whereas the new managerialism appears to be based on the
      expectation of low-trust relations. The paper concludes with a brief look at the
      implications of all these developments for training and education and finds that
      there is still a long way to go before there is any real prospect of providing
      and equipping health care personnel with the requisite skills to enable them to
      meet the complex challenges that are a common characteristic of health care
      systems.

PMID- 8870146
TI  - The impact of globalization on the determination and management of ethical
      choices in the health arena.
AB  - In this paper, the meaning and significance of ethical choices in the arena of
      health under conditions of globalization are explored. The paper first discusses
      globalization, its theorized sources and consequences, exposing connections
      between globalization and local developments in diverse milieux. It is pointed
      out that the ways in which global and local developments interact are related to
      specific socio-historical and cultural configurations of every locality.
      Paradoxes which attend the conceptualization of ethical choices under these
      conditions are highlighted. Finally, conclusions are drawn about how multimethod
      research, including research designed to elicit emic theory, can contribute to an
      understanding of what is implied by the management of ethical choices, and of how
      ethical problems in the health arena can be approached.

PMID- 8870147
TI  - Economic reform and health sector policy: lessons from structural adjustment
      programs.
AB  - From a purely economic perspective, structural adjustment programs (SAPs) and
      economic reform policies are viewed as short-term austerities that lead to long
      term growth and development. These intertemporal trade-offs, however, are not
      always acceptable in health. Unique biologic events such as intrauterine
      development and neural development cannot be postponed even for a short period.
      Health policymakers need to understand the expected and unexpected impacts of
      economic reform on health outcomes in individuals and on the population. The
      interactions are complex, involve multiple sectors, and can be better understood
      by looking at the experience of developing countries over almost fifteen years of
      SAP experience. Health care budgets may be vulnerable to reduced government
      spending, quality of care deteriorates, nutrition will suffer more likely in
      urban areas, and cost-effective preventive programs may stop if labor and capital
      are not properly matched. Health outcomes overall do not appear to suffer but a
      more detailed look, with better data, shows that the incidence of preventable
      diseases rises and irreversible deterioration in health status does occur within
      countries. To prevent this from happening in the future, health policymakers need
      to take a multidisciplinary focus to first understand the effects of economic
      reform and then to plan a coordinated response. Better data, alternative
      financing, and strong political leadership are also important lessons.

PMID- 8870148
TI  - Dava, Daktar, and Dua: anthropology of practiced medicine in India.
AB  - The paper explicates "practiced medicine" as an operative cross-cultural analytic
      concept by locating it within previous major developments and directions of study
      within anthropological studies of medicine in India, and medical anthropology
      more generally. Practiced medicine in India, for example, allows us to see better
      how India manages not only multiple traditional and modern medical approaches,
      languages, therapeutic regimens, and materia medica, but it also leads us to a
      sustained moral, social and material criticism from within. The study of such
      diversity leads to a loosely shared, and ethnographically attestable, cultural
      reasoning, practice and practical ethos across the traditional and modern medical
      worlds. Also appearing before us are the usually hidden cultural assumptions,
      negotiations and compromises of diverse Indian medical practitioners, and the
      strengths and weaknesses of modern medicine under "normal" and "disastrous"
      situations in contemporary India. As India today grapples with issues of
      availability, affordability, equity, and distributive justice in medical care,
      its practiced medicine raises issues of "critical consciousness" for modern (and
      traditional), state supported medicine.

PMID- 8870149
TI  - How religion influences morbidity and health: reflections on natural history,
      salutogenesis and host resistance.
AB  - This paper surveys the field that has come to be known as the epidemiology of
      religion. Epidemiologic study of the impact of religious involvement, broadly
      defined, has become increasingly popular in recent years, although the existence,
      meaning and implications of an apparently salutary religious effect on health
      have not yet been interpreted in an epidemiologic context. This paper attempts to
      remedy this situation by putting the "epidemiology" into the epidemiology of
      religion through discussion of existing empirical findings in terms of several
      substantive epidemiologic concepts. After first providing an overview of key
      research findings and prior reviews of this field, the summary finding of a
      protective religious effect on morbidity is examined in terms of three important
      epidemiologic concepts: the natural history of disease, salutogenesis and host
      resistance. In addition to describing a theoretical basis for interpreting a
      religion-health association, this paper provides an enumeration of common
      misinterpretations of epidemiologic findings for religious involvement, as well
      as an outline of hypothesized pathways, mediating factors, and salutogenic
      mechanisms for respective religious dimensions. It is hoped that these
      reflections will serve both to elevate the status of religion as a construct
      worthy of social-epidemiologic research and to reinvigorate the field of social
      epidemiology.

PMID- 8870150
TI  - Translating research findings into health policy.
AB  - Evidence of the influence of research on health policy is paradoxical. While
      there is scant evidence that research has had any impact on the direction or
      implementation of widespread health reforms, research on evidence-based medicine
      has dramatically increased, despite limited evidence that it has affected
      clinical practice. These developments have occurred in the context of a general
      decline in state intervention and provision and a post-modern questioning of
      researchers' authority. Models of the relationship between research and policy
      range from one where empirical research rationally informs decision-making,
      through research incrementally affecting policy, to an "enlightenment" or
      "infiltration" model, which may operate on a conceptual level. Health research
      that contributes to large-scale socio-political change may require more
      methodological pluralism and greater focus on key institutional structures. Case
      studies reviewed suggest that dissemination is enhanced if researchers involve
      managers and policy-makers in the development of the framework for and focus of
      research and if investigators assume a responsibility for seeing their research
      translated into policy. Public health research is more influential if topical,
      timely, well-funded and carried out by a collaborative team that includes
      academics. Evaluations are more influential if, in addition, they are
      commissioned by health authorities but based on local collection of data, and
      instruments and incentives to implement policy are available. In some areas, such
      as the recent policy focus on careers in the community, researchers were largely
      responsible for raising this policy issue, whereas in other areas, such as the
      relationship between unemployment and health, researchers are just one of the
      groups of experts making competing claims about causality. In conclusion, clear
      research findings are not always a passport to policy, but researchers can
      reframe the way health policy issues are seen, and collaboration with policy
      makers initially can enhance implementation later.

PMID- 8870151
TI  - Urban violence and health--South Africa 1995.
AB  - Many cities all over the world are the loci of various forms of violence.
      Violence is a complex phenomenon, its causes are multidimensional and its
      consequences have ramifications far beyond the immediate perpetrators and
      victims. The aim of this paper is to review various forms of urban violence and
      their health consequences, locating them in the wider South African context.
      Owing to the lack of centralised data, the information presented in this paper is
      based on the best available data derived from numerous sources. Using the socio
      environmental model of health and disease as a framework, violence and its impact
      on health is discussed. The brief review of political violence, violent crimes,
      violence against women and domestic violence in South Africa, highlights the fact
      that SA is a particularly violent society. The data presented suggest a link
      between the social context of violence and its health consequences, dealing with
      the impact of urban violence in the form of physical trauma as well as emotional
      trauma associated with it. Consequently, adopting a comprehensive approach, that
      violence needs to be understood in the wider societal context and has to be dealt
      with in the broadest terms possible, as advocated by the "New Public Health"
      approach, a way forward to reduce levels of violence and cope with its health
      consequences is suggested. An emphasis is placed on the three levels of
      prevention and the vital collaboration between the judicial system, police, the
      health sector as well as the community.

PMID- 8870152
TI  - Urban violence: health consequences and costs.

PMID- 8870153
TI  - Small wars and invisible genocides.

PMID- 8870154
TI  - The population risk as an explanatory variable in research synthesis of clinical
      trials.
AB  - The population risk, for example the control group mortality rate, is an
      aggregate measurement of many important attributes of a clinical trial, such as
      the general health of the patients treated and the experience of the staff
      performing the trial. Plotting measurements of the population risk against the
      treatment effect estimates for a group of clinical trials may reveal an apparent
      association, suggesting that differences in the population risk might explain
      heterogeneity in the results of clinical trials. In this paper we consider using
      estimates of population risk to explain treatment effect heterogeneity, and show
      that using these estimates as fixed covariates will result in bias. This bias
      depends on the treatment effect and population risk definitions chosen, and the
      magnitude of measurement errors. To account for the effect of measurement error,
      we represent clinical trials in a bivariate two-level hierarchical model, and
      show how to estimate the parameters of the model by both maximum likelihood and
      Bayes procedures. We use two examples to demonstrate the method.

PMID- 8870155
TI  - An alternative to the use of two-sided tests in clinical trials.
AB  - There is a controversy in the literature concerning the use of one- and two-sided
      tests in clinical trials. Some contend that, when the research question relates
      to improved efficacy or safety, that is, the expected change is in one direction
      only, the hypothesis test should reflect this by being one-sided. Others insist
      on the use of a two-sided test in case a treatment difference in the opposite
      direction to that expected might turn up. We propose an alternative procedure to
      the two-sided test which also provides protection against overlooking a negative
      effect. The proposed procedure tests simultaneously for a positive difference and
      for equivalence. We illustrate the procedure by applying it to the results of a
      recent clinical trial.

PMID- 8870156
TI  - Some optimal and non-optimal two-stage designs using an alpha-spending function.
AB  - While designing a group sequential clinical trial in the pharmaceutical industry
      setting, we often face a problem of determining the time for an interim analysis.
      For a two-stage trial we compute the sample sizes n and N per treatment group for
      the interim and final analyses, respectively, that minimize the average trial
      size for a specified overall power. We consider this optimization when we monitor
      the trial using a Lan-DeMets alpha-spending function. Two additional problems
      considered in this context are (i) finding the sample sizes that maximize the
      overall power for a specified average trial size, and (ii) finding the sample
      sizes that achieve specified powers at the interim and final analyses.

PMID- 8870157
TI  - Statistical analysis of possible bias of clinical judgements due to observing an
      on-therapy marker variable.
AB  - In certain double-blind clinical trials there is the possibility that certain
      'marker variables' observable during the trial may in part unblind the trial,
      even at a subliminal level. At issue is whether or not this potential unblinding
      biases the investigators' clinical efficacy assessments. This issue arose after
      the completion of three clinical trials that compared tretinoin emollient cream
      (TEC) 0.05 per cent to its vehicle in patients with photodamaged skin. The
      question raised was whether or not possible 'subliminal unblinding' of the
      investigators and patients, due to the cutaneous irritation associated with
      topical tretinoin, might have caused a treatment bias in the study. To address
      this issue, we undertook a reanalysis of these three clinical trials. In doing
      so, we develop in this paper a statistical modelling approach to address issues
      of possible bias introduced by the ability to observe such marker variables. The
      approach utilizes a linear discriminant analysis to introduce an auxiliary
      categorical variable for the efficacy analysis. A suitable categorical data model
      permits the estimation of relevant bias effects. We illustrate this approach with
      data from the three TEC 0.05 per cent trials.

PMID- 8870158
TI  - Non-parametric Bayesian approach to hazard regression: a case study with a large
      number of missing covariate values.
AB  - A 'packaged' non-parametric multiplicative hazard regression model is proposed,
      and applied to a study of the effects of some genetic and viral factors in the
      development of spontaneous leukaemia in mice. Hierarchical modelling and data
      augmentation are used to deal with the large number of missing covariate values.
      A Bayesian procedure is adopted, and the Metropolis-Hastings algorithm is used in
      the numerical computation of the posterior distribution.

PMID- 8870159
TI  - The semi-proportional hazards model revisited: practical reparametrizations.
AB  - Reformulations of the semi-proportional hazards model are outlined making
      estimation and testing of stratum-covariate interaction effects easily accessible
      within the framework of the stratified Cox proportional hazards model. The method
      is illustrated by a practical analysis of variables influencing bronchial
      responsiveness with data from the Hordaland study of obstructive lung disease.

PMID- 8870160
TI  - Comparison of trends in HIV infection for two risk categories.
AB  - Sensible plans for health-care needs and determination of priorities for
      expenditure require regular assessment of trends in HIV incidences. In
      particular, trends in the relative HIV incidences of different risk categories
      are useful when assessing whether current control strategies are working equally
      well for all risk categories. Here five tests for such trends are proposed for
      the analysis of AIDS incidence data and their performances are compared by a
      simulation study, assuming a log-linear trend in the HIV incidences for two risk
      categories. A convenient test based on a log-linear model for AIDS incidences is
      found both effective and robust to the nature of the underlying trend. The
      maximum likelihood estimate of the trend parameter is found stable even though
      estimates of other HIV incidence parameters are unstable. Smoothing of estimates
      of the other HIV incidence parameters is recommended because this dramatically
      reduces the rate of convergence of the iterative methods used to obtain the
      estimates.

PMID- 8870161
TI  - A comparison of statistical methods for clustered data analysis with Gaussian
      error.
AB  - We investigate by simulation the properties of four different estimation
      procedures under a linear model for correlated data with Gaussian error: maximum
      likelihood based on the normal mixed linear model; generalized estimating
      equations; a four-stage method, and a bootstrap method that resamples clusters
      rather than individuals. We pay special attention to the group randomized trials
      where the number of independent clusters is small, cluster sizes are big, and the
      correlation within the cluster is weak. We show that for balanced and near
      balanced data when the number of independent clusters is small (< or = 10), the
      bootstrap is superior if analysts do not want to impose strong distribution and
      covariance structure assumptions. Otherwise, ML and four-stage methods are
      slightly better. All four methods perform well when the number of independent
      clusters reaches 50.

PMID- 8870162
TI  - Ordinal regression methodology for ROC curves derived from correlated data.
AB  - We present an approach for the analysis of correlated ROC data, using ordinal
      regression models in conjunction with generalized estimating equations. The
      approach applies to the analysis of degree-of-suspicion data derived from
      multiple interpretations of the same diagnostic study and from the examination of
      the same patients with multiple diagnostic modalities. The regression models make
      it possible to incorporate patient and reader characteristics into the analysis,
      without having to resort to stratification. We illustrate the potential of the
      approach with analysis of data from two studies in diagnostic oncology.

PMID- 8870163
TI  - Differential effect of adrenocorticosteroids on 11 beta-hydroxysteroid
      dehydrogenase bioactivity at the anterior pituitary and hypothalamus in rats.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) is a microsomal enzyme that
      catalyzes the dehydrogenation of cortisol (F) to cortisone (E) in man and
      corticosterone (B) to 11-dehydrocorticosterone (A) in rats. 11 beta-OHSD has been
      identified in a wide variety of tissues. The differential distribution of 11 beta
      OHSD suggests that this enzyme has locally defined functions that vary from
      region to region. The aim of this study was to investigate the effects of the
      glucocorticoids B and dexamethasone (DM), the mineralocorticoid
      deoxycorticosterone (DOC), and the inhibitors of 11 beta-OHSD glycyrrhizic acid
      (Gl) and glycyrrhetinic acid (GE) on 11 beta-OHSD bioactivity at the hypothalamus
      (HT) and anterior pituitary (AP). Male Wistar rats were treated with GI or were
      adrenalectomized (ADX) and treated with either B, DM, or DOC for 7 days. All
      treatments were in vivo except GE, which was used in vitro. At the end of
      treatment, homogenates of HT and AP were assayed for 11 beta-OHSD bioactivity,
      expressed as the percentage conversion of B to A in the presence of NADP, 11 beta
      OHSD bioactivity is significantly higher (P < 0.0001) in the AP compared with the
      HT. Adrenalectomy significantly increased the enzyme activity in the AP (P <
      0.05), an effect reversed by B or DM. ADX rats treated with DOC showed decreased
      enzyme activity in the AP (P < 0.001) but increased the activity in the HT (P <
      0.0001). Gl increased activity in both HT and AP, whereas GE decreased activity
      significantly. We conclude that the modulation of 11 beta-OHSD is both steroid
      specific and tissue specific.

PMID- 8870164
TI  - Steroidal allylic fluorination using diethylaminosulfur trifluoride: a convenient
      method for the synthesis of 3 beta-acetoxy-7 alpha- and 7 beta-fluoroandrost-5-en
      17-one.
AB  - This paper discusses our findings regarding fluorination of the diastereomeric 3
      beta-acetoxy-7-hydroxyandrost-5-en-17-ones (3 and 4) at the allylic 7-hydroxyl
      group using diethylaminosulfur trifluoride under various experimental conditions.
      The reaction led to the formation of allylic 7 alpha- and 7 beta-fluoro
      derivatives, 6 and 7, contaminated with small amounts of 3 beta-acetoxy-5 alpha
      fluoroandrost-6-en-17-one (8), the rearrangement product, and 3 beta
      acetoxyandrosta-4,6-dien-17-one (9), the elimination product. However, synthesis
      of 3 beta-acetoxy-7 alpha-fluoroandrost-5-en-17-one (6) and 3 beta-acetoxy-7 beta
      fluoroandrost-5-en-17-one (7) has been achieved in high isomeric purity by
      careful manipulation of the experimental conditions. Also included herein is a
      convenient chemical synthesis of pure 3 beta-acetoxy-7 alpha-hydroxyandrost-5-en
      17-one (4) and 3 beta-acetoxy-7 beta-hydroxyandrost-5-en-17-one (3), the starting
      materials for the present fluorination reaction. The structure of a degradation
      product, 3 beta-acetoxy-5 alpha-hydroxyandrost-6-en-17-one (5), has been
      established by X-ray diffraction analysis to ascertain unambiguously its absolute
      configuration.

PMID- 8870165
TI  - Urinary markers of estrogen metabolism 2- and 16 alpha-hydroxylation in
      premenopausal women.
AB  - There is considerable scientific interest in whether measurement of the major
      estrogen metabolites 2- and 16 alpha-hydroxyestrone will shed light on the role
      of estrogen in the risk of breast cancer. These have been difficult to measure in
      large numbers because of the need for radiolabeled tracers, but a new assay is
      able to utilize spot urine samples. The main objective of this study was to
      assess the reliability of a newly developed enzyme immunoassay (EIA) for the
      measurement of 2- and 16 alpha-hydroxyestrone in urine samples collected from a
      large group of healthy premenopausal women enrolled in a clinical trial A
      secondary objective was to assess the impact of several factors such as body
      weight on the urinary estrogen metabolite ratios. The study cohort included 174
      women aged 44-50, who were enrolled in the Cardiovascular Risk Factors and
      Menopause Trial, also referred to as the Women's Healthy Lifestyle Project
      (WHLP), an ongoing 5-year clinical trial of 535 premenopausal women randomized
      either to an intensive dietary life-style intervention group or to an assessment
      only control group. Measurements of 2- and 16 alpha-hydroxyestrone showed a high
      intraclass correlation for blind duplicate urine samples (R = 0.94 and R = 0.80),
      cross-sectionally and over time (R = 0.79 and R = 0.62), in this population of
      healthy premenopausal women. The intervention diet (of 25% of total calories from
      fat) did not appear to influence the estrogen metabolite ratio. This new estrogen
      metabolite EIA demonstrates good reliability and thus may be appropriate for use
      in large epidemiologic studies of estrogen-related diseases. There was no
      relation between dietary fat reduction, weight loss, and increased exercise and
      change in the ratio among premenopausal women in this study.

PMID- 8870166
TI  - Effect of estrogen on the expression of galanin mRNA in pituitary tumor-sensitive
      and tumor-resistant rat strains.
AB  - The hypothesis that estrogen-induced pituitary tumors are mediated by the
      neuropeptide galanin was tested using tumor-resistant (Sprague-Dawley; SD) and
      tumor-sensitive (Fischer 344; F344) rat strains. Diethylstilbestrol (DES)
      increased expression of galamin mRNA in both strains after 1, 2, and 4 weeks of
      treatment and doubled pituitary weights in F344 rats while pituitary weights in
      SD rats were unchanged by DES treatment. In F344 rats, both the expression of
      galanin mRNA and pituitary weights increased linearly with the length of DES
      treatment. In SD rats however, despite increasing levels of galanin mRNA,
      pituitary weights did not increase. These data indicate that galanin gene
      expression, by itself, is not sufficient to account for increased pituitary
      growth. However, our data do not rule out the possibility that galanin has an
      indirect role in promoting pituitary growth.

PMID- 8870167
TI  - A history of steroid chemistry: some contributions from European industry.

PMID- 8870168
TI  - The rise and fall of the British Drug Houses, Ltd.
AB  - Steroid research at BDH began in earnest in 1946-1948, when Hartley and Petrow
      joined the company. With the need to find new progestational agents to replace
      ethisterone and progesterone, the company began work. They were the first to
      discover the vital importance of 6-methylation in enhancing the hormonal effects
      of steroid hormones. Their progestational studies led them to work on
      antifertility agents and the development of ovulation inhibitors, the mini-pill,
      and preliminary studies on the postcoital pill. Their search for new steroids
      additionally resulted in synthesis for biological evaluation of new corticoids,
      anabolic agents, estrogens, and mineralocorticoids. In 1968 the company, then
      known as The BDH Group Ltd., was incorporated into the Glaxo Group and company
      research terminated.

PMID- 8870169
TI  - Steroid research at Organon in the golden 1950s and the following years.

PMID- 8870170
TI  - Between basic and applied research: Ciba's involvement in steroids in the 1950s
      and 1960s.
AB  - Through its collaboration with the ETH in Zurich (Ruzicka's group) and later on
      with the University of Basel (Reichstein's group). Ciba became involved very
      early in steroid chemistry. The main task of the chemists consisted at that time
      of the synthesis of natural hormones and their derivatives. Cholesterol served
      for several years as the preferred starting material, and efficient procedures
      were developed for its degradation to suitable intermediates. Total syntheses of
      estrogenic substances were pursued independently. Up to the mid-1950s the search
      for alternative starting materials, like hecogenin were intensively investigated.
      In a later period, collaboration with various companies in the United States and
      in Europe stimulated Ciba's involvement in the corticoids, especially the
      dermatocorticoids (Locorten, Sicorten, Miracortene/Ultravate). In line with
      Ciba's traditionally strong engagement in process development, during the period
      described in this report a major effort, was directed towards the isolation and
      synthesis of aldosterone, the most active natural mineralocorticoid. In
      connection with its partial synthesis, new intramolecular radical reactions
      (e.g., the lead(IV) acetate and the hypoiodite reaction) were discovered and
      studied. Although, from the commercial point of view, aldosterone did not meet
      our expectations, the application of these new reactions to the synthesis of 19
      norsteroids opened for Ciba the road to progestins and related compounds.

PMID- 8870171
TI  - Effect of suramin on the biological activity of the two isoforms of the rat 5
      alpha-reductase.

PMID- 8870172
TI  - Measurement of anti-factor IX IgG subclasses in haemophilia B patients who
      developed inhibitors with episodes of allergic reactions to factor IX
      concentrates.
AB  - We have established a simple enzyme-linked immunosorbent assay (ELISA) for the
      detection of anti-factor IX IgG subclasses in haemophilia B patients with
      inhibitors. The assay was performed using immobilized purified factor IX.
      Specific IgG subclasses were detected by peroxidase-conjugated anti-human
      IgG1,2,3 and 4. Ten plasma samples from 6 haemophilia B patients with inhibitors
      ranging from 1.0 to 253 Bethesda Units/ml were analyzed. All samples were
      positive for IgG4. Six out of 10 samples were positive only for IgG4. Three
      samples were positive for IgG2. Five of the 6 patients had previously had
      allergic reactions to factor IX concentrates. Three patients had allergic
      episodes within the past month. Three samples from these latter patients taken on
      the day when the allergy had occurred showed positive also for IgG1. In later
      samples, however, taken at 4 days and 4 weeks respectively from two of these same
      patients. IgG1 was not detected. In two of the five patients in whom allergic
      reactions had occurred more than one month previously IgG1 was not detected. The
      results suggested that allergic reactions in patients with haemophilia B treated
      with factor IX concentrates were associated with the development of the specific
      IgG1 subclass of antibody to factor IX.

PMID- 8870173
TI  - Interest of a simple and fast method for platelet von Willebrand factor
      characterization.
AB  - Quantitative or qualitative assay of platelet von Willebrand factor (vWF) is
      required for the classification of patients suffering from von Willebrand disease
      (vWD). The major interest of this classification is the administration of
      specific and appropriate treatment to each category of vWD patients. However,
      because platelet lysate is prepared from washed platelets, the analysis of
      platelet vWF is not performed in routine. To overcome this problem, platelet
      lysates were prepared either with a new method which does not require washing
      procedure or with the established protocol, then respective platelet vWF
      characteristics were compared. Our data show that the two methods provide
      comparable information required for the characterization of types 1 and 2 vWD
      patients. With this new procedure, complete phenotypic data including the
      characteristics of platelet vWF can be obtained from most of the vWD patients.

PMID- 8870174
TI  - Platelet and blood clotting activation in patients with mitral valve prolapse.
AB  - In patients with mitral valve prolapse (MVP) a high incidence of valvular
      abnormalities with a history of previous cerebrovascular disease has been
      reported and an embolic mechanism has been proposed. Aim of this study is the
      study of platelet and coagulation activation in patients with MVP. Fifty-four
      patients affected by MVP (mean age 46 +/- 15 yrs, 22 males, 32 females) and 50
      control subjects, age- and sex-matched, were tested for platelet activation [P
      selectin and GpIIb-IIIa platelet surface expression at rest and after stimuli by
      flow cytometric analysis, Beta-Thromboglobulin (TG) and Platelet Factor 4 (PF4)
      plasma levels by ELISA, platelet-rich-plasma (PRP) and whole blood spontaneous
      platelet aggregation (SPA)] and for activation of blood coagulation (Prothrombin
      activation fragment F1+2 plasma levels by ELISA). P-selectin, GpIIb-IIIa
      expression, Beta-TG, PF4 and SPA were found similar in MVP patients and in
      controls. However, in patients with severe mitral regurgitation (MR) the
      percentage of activated platelets which express P-selectin after stimuli was
      slightly but significantly (p < 0.05) lower in comparison to MVP patients without
      or with mild to moderate MR and to controls. Moreover, in patients with severe MR
      F1+2 levels (median 1.6 nmol/L, range 0.6-2.6 nmol/L) were significantly higher
      (p < 0.001) than both in controls (median 0.95 nmol/L, range 0.2-1.4 nmol/L) and
      in patients without or with mild to moderate MR (median 1.0 nmol/L, range 0.4-2.3
      nmol/L). Our findings suggest that MVP is not responsible per se for blood
      clotting activation, but in patients with severe mitral insufficiency an increase
      in thrombin generation can occur. These alterations in hemostatic system may
      represent a mechanism by which MR increases the risk of thromboembolic events in
      patients with MVP.

PMID- 8870175
TI  - Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human
      peripheral blood monocytes to express tissue factor.
AB  - Monocytes induced to express tissue factor (TF), the initiator of the clotting
      cascade, might play an important role in the pathogenesis of atherosclerosis. We
      have investigated the TF-inducing capacity of two factors thought to be involved
      in atherogenesis, i.e. the platelet derived growth factor-BB (PDGF-BB) and
      monocyte chemotactic protein-1 (MCP-1), a member of the chemokine superfamily.
      PDGF-BB and MCP-1 are potent chemotactic and activating factors for human blood
      monocytes. alpha-thrombin which is known to induce TF in endothelial cells and
      that recently has been shown to induce secretion of MCP-1 from endothelial cells
      and monocytes was also studied. PDGF-BB induced a dose-dependent expression of TF
      antigen in monocytes with maximal response at 20-50 ng/mL. At higher
      concentrations the expression was reduced. No synergistic effect between PDGF-BB
      and LPS was seen. MCP-1 also induced a dose-dependent TF-expression with maximal
      response at 50 ng/mL. In contrast to these results thrombin did not. MCP-1 had a
      slight, but not significant, priming effect on LPS-induced TF expression. These
      data show that PDGF-BB and MCP-1 are potent inducers of TF in human peripheral
      blood monocytes. We suggest that this TF-induction might be an important link
      between hemostasis and inflammation.

PMID- 8870176
TI  - Systemic release of thrombomodulin, but not from the cardioplegic, reperfused
      heart during open heart surgery.
AB  - Thrombomodulin is a potential marker of endothelial injury. Plasma thrombomodulin
      was measured in concomitant arterial and coronary sinus samples in 9 patients
      undergoing elective coronary artery bypass surgery with cardiopulmonary bypass
      (CPB, 88 +/- 14 min) (mean +/- SD) and cold, crystalloid, antegrade cardioplegia
      (44 +/- 14 min). Arterial thrombomodulin was 17 +/- 6 ng/ml before surgery, and
      decreased to 10 +/- 5 ng/ml after heparinization (p < 0.008 compared to initial
      value). During CPB thrombomodulin increased, with a maximal level of 23 +/- 7
      ng/ml (p < 0.008 vs initial value) 40 min after aortic declamping. No difference
      between arterial and coronary sinus concentrations was detected during
      reperfusion of the heart. In conclusion, plasma thrombomodulin is decreased by
      heparin, and increased during CPB. Consequently, thrombomodulin may be used to
      evaluate endothelial injury during CPB. However, as there is no specific
      intracoronary release of thrombomodulin during reperfusion, thrombomodulin is not
      a suitable marker of coronary endothelial injury after cardioplegia.

PMID- 8870177
TI  - Is platelet phospholipid-dependent thrombin generation altered by acute
      myocardial infarction or aspirin?
AB  - The ability of unactivated and calcium ionophore activated platelets to support
      thrombin generation in defibrinated plasma was measured by a chromogenic
      substrate assay in the absence of clot formation. Platelet phospholipid-dependent
      thrombin generation (Platelet-TG) could be measured using platelets isolated from
      blood collected into either sodium citrate or EDTA as anticoagulant. Measurements
      were stable in samples kept at room temperature for 24 hours after venesection.
      There was no significant difference in either the unactivated or activated
      platelet-TG with platelets collected into either anticoagulant (mean difference
      10.12 nmol/min unactivated and 10.60 nmol/min activated). There was no
      correlation between unactivated and activated platelet-TG and patient age.
      Platelet-TG was 179 (153-237) nmol/min (median and inter quartile range) for
      unactivated and 489 (462-508) nmol/min for activated platelets from healthy
      volunteer subjects (median age 31, range 20-40 years). Platelet-TG was the same
      in subjects from a population-based cohort study (median age 58, range 45-70
      years [162 (142-193) nmol/min and 527 (490-551) nmol/min, unactivated and
      activated platelets respectively] as compared to patients admitted with acute
      myocardial infarction (median age 68, range 36-85 years [179 (146-200) nmol/min
      and 473 (440-517) nmol/min unactivated and activated platelets respectively] (p =
      0.497 for comparison between unactivated platelet-TGs and p = 0.487 for
      comparison between activated platelet-TGs in the two groups). Aspirin inhibited
      platelet aggregation but did not affect platelet-TG using either unactivated or
      activated platelets exposed to aspirin in vitro; or in vivo, using platelets
      obtained from individuals after ingestion of aspirin. In conclusion these results
      show that for measurement of platelet-TG, blood samples can be anticoagulated
      with EDTA as well as sodium citrate for up to 24 hours after venesection and that
      this measurement is not affected by subject age, aspirin treatment or the acute
      stage of myocardial infarction.

PMID- 8870178
TI  - Lupus anticoagulant and a functional assay for tissue factor pathway inhibitor.

PMID- 8870179
TI  - MR of the brain in children.
AB  - MR imaging has firmly established its place as the cornerstone of pediatric
      neuroimaging. Recent advances in MR imaging have led to decreased imaging time,
      high resolution studies, and new methods for obtaining tissue contrast. Magnetic
      resonance angiography (MRA) now obviates the need for angiography in some
      children, although its extended role is still to be defined. Normal and abnormal
      development and myelination patterns have been further defined with MR imaging.
      The patterns of brain injury resulting from hypoxia and ischemia vary with the
      degree of the insult as well as the gestational age of the child. These patterns
      of hypoxic-ischemic encephalopathy can be analyzed to determine when the insult
      occurred. Neuronal migration disorders and phakomatoses can be diagnosed with
      confidence at an early age, thus facilitating genetic counseling. MR imaging can
      detect the most common lesions associated with childhood epilepsy, such as
      hippocampal sclerosis, focal cortical dysplasias, and low-grade tumors. Other
      areas, including pediatric AIDS, toxicity-related injury, metabolic/mitochondrial
      conditions, and disorders associated with iatrogenic injury, can be diagnosed
      with MR. Spectroscopy provides information that should prove useful in evaluating
      and monitoring neuronal and other brain tissue disorders in children.

PMID- 8870180
TI  - Magnetization transfer magnetic resonance imaging: a clinical review.
AB  - Magnetic resonance imaging has traditionally used the T1 and T2 relaxation times
      and proton density (PD) of tissue water (hydrogen protons) to manipulate
      contrast. Magnetization transfer (MT) is a new form of tissue contrast based on
      the physical concept that tissues contain two or more separate populations of
      hydrogen protons: a highly mobile (free) hydrogen (water) pool, Hr, and an
      immobile (restricted) hydrogen pool, Hr, the latter being those protons bound to
      large macromolecular proteins and lipids, such as those found in such cellular
      membranes as myelin. Direct observation of the Hr magnetization pool is normally
      not possible because of its extremely short T2 time (< 200 microseconds). But
      saturation of the restricted pool will have a detectable effect on the mobile
      (free) proton pool. Saturation of the restricted pool decreases the signal of the
      free pool by transferring the restricted pool's saturation. Exchange of
      magnetization between the free and restricted hydrogen protons is a substantial
      mechanism for spin-lattice (T1) relaxation in tissues and the physical basis of
      MT. Through an appropriately designed pulse sequence, magnetization transfer
      contrast (MTC) can be produced. MT contrast is different from T1, T2, and PD, and
      it likely reflects the structural integrity of the tissue being imaged. A variety
      of clinically important uses of MT have emerged. In this clinical review of the
      neuroradiological applications of MT, we briefly review the physics of MT, the
      appearance of normal brain with MT, and the use of MT as a method of contrast
      enhancement/background suppression and in tissue characterization, such as
      evaluation of multiple sclerosis and other white-matter lesions and tumors. The
      role of MT in small-vessel visualization on three-dimensional time-of-flight
      magnetic resonance angiography and in head and neck disease and newer
      applications of MT are also elaborated.

PMID- 8870181
TI  - MRI of avascular necrosis of bone.
AB  - Avascular necrosis (AVN) is characterized by death of both trabecular bone as
      well as bone marrow elements. Weight-bearing bone becomes mechanically weakened
      and may eventually collapse, secondarily leading to osteoarthritis and
      debilitating pain. Early diagnosis and treatment of this entity are crucial
      because it affects relatively young individuals, and treatment options for
      advanced disease are limited. Magnetic resonance imaging (MRI) has emerged as the
      modality of choice for the evaluation of avascular necrosis of bone. We will
      discuss applications of MRI for early diagnosis, for monitoring therapy, and for
      its potential role in assessing individuals at risk of AVN. Although bone
      scintigraphy using single photon emission computed tomography (CT) may be nearly
      as accurate as MRI, MRI offers a more specific diagnosis in the patient who
      presents with hip pain of uncertain etiology. In addition, lesion size and
      location can be more easily assessed on magnetic resonance images, and this has
      been shown to relate to prognosis and need for treatment. We will review the
      pathophysiologic mechanisms of AVN and the current use of MRI in the diagnosis of
      this condition.

PMID- 8870182
TI  - Fifty years of blood transfusion.

PMID- 8870183
TI  - Feline calicivirus strain differentiation using monoclonal antibody analysis in
      an enzyme-linked immuno-flow-assay.
AB  - Six monoclonal antibodies raised against feline calicivirus (FCV) strain F9 were
      used in an enzyme-linked immuno-flow-assay (ELIFA) to analyse 55 isolates of FCV.
      Forty seven field isolates were obtained from cats with acute oral/respiratory
      disease, chronic oral lesions, and from cats showing vaccine reactions, i.e.
      clinical signs of FCV infection shortly after vaccination. Eight reference
      strains including F9 and three vaccine strains based on F9 were also examined.
      All of the strains of F9, derived from various sources, reacted with all six of
      the monoclonal antibodies, whereas some of the field isolates did not react with
      any. In general, the field isolates showed a spectrum of reactivities and
      selected isolates could be distinguished. However, there were no clear cut
      differences between the clinical groups. Overall, the oral/respiratory group
      showed less reactivity with the monoclonals, suggesting they were less related to
      F9. Although the other groups appeared to be more closely related to F9, none of
      the isolates tested reacted with all six monoclonal antibodies.

PMID- 8870185
TI  - Vaginal and rectal infection of cats with feline immunodeficiency virus.
AB  - The objective of this study was to examine the potential of vaginal and rectal
      mucosal routes for feline immunodeficiency virus (FIV) uptake and infection, as a
      model of mucosal HIV infection, and to determine the fate of virus at these
      mucosal sites following transmission of infection. SPF cats were exposed to FIV
      isolates (PET, GL-8, T637), administered as either cell-associated or cell-free
      inocula, via the rectum or vagina. Establishment of infection was confirmed by
      isolation of infectious FIV from peripheral blood mononuclear cells (PBMC), and
      by presence of FIV proviral DNA in PBMC using a nested polymerase chain reaction.
      Fate of virus in tissue taken at necropsy from cats infected for 6-48 weeks was
      assessed by localizing FIV core and envelope proteins, p24 and gp41, using a
      biotin-streptavidin linked immunoperoxidase (IP) technique. Cells susceptible to
      infection were identified by an in situ hybridization technique for FIV viral DNA
      and RNA. Cell-free, as well as cell-associated, virus was infectious across
      intact vaginal and rectal mucosal surfaces. Transmission was most successful
      using cell-associated inocula, and via the rectal route. Cells infected with FIV
      were detected by IP staining in the colon of 6/9 rectally challenged cats and 1/5
      vaginally challenged cats. Virus was predominantly localized within the
      epithelium at the base of the colonic crypts associated with lymphoid aggregates
      (follicle associated epithelium; FAE), and within the lymphoid follicle itself.
      Occasional infected cells were also noted within the lamina propria. The
      distribution of FIV DNA positive cells in the colon was similar to that for FIV
      antigen whilst FIV RNA positive cells were found more extensively, including
      within the lamina propria and lymphoid follicle. FIV infected cells were not
      detected within the vagina, or colonic and ileac lymph nodes. Similar patterns of
      infected cells were seen in all of the positive cats, indicating that colonic
      tissues remain persistently actively infected with FIV. We conclude that the
      FIV/cat model of rectal and vaginal mucosal infection should prove useful for
      characterizing the mechanism by which HIV infects mucosal surfaces and as a
      challenge system for the design of vaccines effective at preventing HIV infection
      via rectal and vaginal routes.

PMID- 8870184
TI  - The isolation of peste des petits ruminants virus from northern India.
AB  - The aetiological agent responsible for an epizootic of a rinderpest-like disease
      afflicting sheep and goats in three states of northern India was confirmed as
      peste des petits ruminants virus. To differentiate the virus from rinderpest a
      number of diagnostic tests were used, including immunocapture ELISA, specific
      oligonucleotide primers in a reverse transcriptase polymerase chain reaction,
      immunofluorescence with virus specific monoclonal antibodies and virus isolation.
      The virulence profile of one isolate in cattle sheep and goats was established.
      Infected animals developed specific antibody responses and excreted specific
      antigen in their lachrymal secretions.

PMID- 8870186
TI  - Protection of pigs by vaccination of pregnant sows against eastern equine
      encephalomyelitis virus.
AB  - Serum-virus neutralizing antibodies were detected in serum and colostrum of sows
      vaccinated during pregnancy with commercially available vaccines against eastern
      equine encephalomyelitis virus (EEEV), and antibodies were detected in serum from
      nearly all pigs from vaccinated sows following colostrum uptake. Serum-virus
      neutralizing antibody (SVN) test titers were measured in colostrum and pigs at
      the next farrowing, and additional vaccination of sows prior to the third
      farrowing led to elevated SVN titers in serum, colostrum and all pigs. Six pigs
      from vaccinated sows challenged at 8 to 9 days of age with 1 x 10(6) TCID50 EEEV
      did not develop the high temperatures or signs of central nervous system disease
      that 6 pigs from non-vaccinated sows developed. Virus was isolate from blood and
      oropharyngeal swabs from all pigs from non-vaccinated sows with blood virus
      titers as high as 9.3 x 10(4) TCID50, while only low levels of virus were
      detected in blood and oropharyngeal swabs from pigs from vaccinated sows. Virus
      was also isolated from tonsils collected at necropsy from 3 pigs from non
      vaccinated and 1 pig from vaccinated sows. Vaccination of pregnant sows leads to
      development of maternal antibodies that are transmitted via colostrum to pigs and
      are protective against clinical EEEV related disease after experimental challenge
      with EEEV. In addition, vaccination prevents amplification of virus in infected
      pigs and could result in protection of animals and farm labor in the environment
      of infected pigs.

PMID- 8870187
TI  - The VP4 and VP7 of bovine rotavirus VMRI are antigenically and genetically
      closely related to P-type 5, G-type 6 strains.
AB  - We have previously reported the isolation of a bovine rotavirus, designated VMRI,
      with a super-short electropherotype. We have characterized this strain further as
      it has shown antigenic differences with the prototype G6 strain NCDV-Lincoln. In
      this communication, we report the antigenic and molecular characterization and
      the nucleotide sequence of the VP4 and VP7 genes of this strain. Virus
      neutralization tests indicated 2- to 13-fold differences in the titers between
      NCDV-Lincoln, B641 and VMRI strains. Northern blot hybridization results
      indicated a degree of heterogeneity in the VP4 gene of these strains which can be
      detected under conditions of high stringency. The VP4 and VP7 genes of the VMRI
      strain were cloned and sequenced and compared with the published sequences of
      other bovine rotavirus strains. The VP4 gene of VMRI had a high degree of
      homology with that of UK and B641 strains but differed significantly from that of
      both NCDV-Lincoln and B223 strains. Sequence analysis of the VP7 gene of VMRI and
      other strains indicated a high degree of conservation and the amino acid identity
      between the different strains was 96%. Sequence information regarding these
      strains and field isolates will assist in the generation of effective vaccination
      strategies for control of neonatal calf diarrhea.

PMID- 8870188
TI  - Porcine reproductive and respiratory syndrome virus (PRRSV): monoclonal
      antibodies detect common epitopes on two viral proteins of European and U.S.
      isolates.
AB  - Sixteen hybridoma cell lines secreting monoclonal antibodies (mAbs) directed
      against two dutch isolates of the causative virus of Porcine Reproductive and
      Respiratory Syndrome (PRRSV) were produced. The hybridoma cells resulted from
      fusions of SP2/0 myeloma cells with splenocytes of STU mice immunized with
      purified PRRSV after induction of immunotolerance against host cell constituents.
      Screening of supernatant fluids was performed by an indirect immunofluorescence
      assay on PRRSV-infected porcine alveolar macrophages. Immunoblotting studies
      revealed that the mAbs had different protein specificities. One mAb reacted with
      a viral 15 kD protein, eleven were directed against a 40-50 kD protein, and four
      against a 30-40 kD protein. The mAb against the 15 kD putative nucleocapsid
      protein as well as five mAbs against the 40-50 kD protein recognized epitopes on
      these proteins which are conserved in various European and U.S. isolates of
      PRRSV.

PMID- 8870189
TI  - Canine parvovirus binds to multiple cellular membrane proteins from both
      permissive and nonpermissive cell lines.
AB  - For identification of canine parvovirus (CPV) binding protein, the SDS
      solubilized cell membrane fraction from a permissive cell line. CRPK, was
      subjected to the virus overlay protein blot assay (VOPBA). Competitive inhibition
      experiments showed the presence of multiple CPV-binding proteins with molecular
      masses of 36, 35, 33, 31, 29, 27, 25, and 23 kDa. CPV-binding proteins of same
      molecular masses were also detected in membrane fractions from nonpermissive, as
      well as other permissive, cell lines. We confirm that the mechanism of
      nonpermissiveness to CPV is not operative at the cellular attachment level.

PMID- 8870190
TI  - Diversity among abortion strains of Chlamydia psittaci demonstrated by inclusion
      morphology, polypeptide profiles and monoclonal antibodies.
AB  - Twenty eight C. psittaci abortion strains had been previously classified in to 4
      immunologically distinct groups on the basis of cross-protection experiments in a
      mouse model. To identify the molecular basis of their immunological divergence 4
      representative strains were investigated by cellular, molecular and immunological
      techniques. An identical pattern was obtained by Alul digestion of the amplified
      major outer membrane protein gene (MOMP) by the polymerase chain reaction (PCR)
      of the 4 strains. However, inclusion morphology and polypeptide profiles clearly
      distinguished one strain, named LLG, and its homologous strain POS from the other
      prototypes by the presence of a unique protein at 26.5 kDa and the absence of a
      polypeptide at 23 kDa. Six out of 10 monoclonal antibodies (mAbs) raised against
      abortion strains failed to react with inclusions of the 2 strains. All 6 mAbs
      reacted with the chlamydial outer membrane complex (COMC). Two of these mAbs, one
      against the MOMP and one against an antigen at 90 kDa, did not react with
      immunoblots of LLG and POS. The data provide direct demonstration of the
      existence of strain variation in the field and classify strains LLG and POS as a
      distinct C. psittaci serotype 1-subtype. The antigenic diversity among abortion
      strains should be taken into consideration when designing a subunit vaccine.

PMID- 8870191
TI  - Diversity of energy-yielding substrates and metabolism in avian mycoplasmas.
AB  - The metabolism of organic substrates and production of H2O2, a potential
      pathogenicity factor, were studied in the type strains of fourteen avian
      Mycoplasma species, and in low-passage isolates of M. gallinarum, M.
      gallisepticum, M. iners and M. pullorum. Substrates were added to cell
      suspensions in Ringer or saline solution and oxygen uptake and/or change in pH
      monitored. The fermentative species could be sub-divided according to whether O2
      uptake did (M. anatis, M. columborale, M. gallisepticum, M. imitans and M. iowae)
      or did not (M. gallinaceum, M. gallopavonis and M. pullorum) accompany glucose
      metabolism and the five non-fermentative, arginine-hydrolysing strains according
      to whether organic acids (lactate, 2-oxobutyrate, pyruvate) were (M.
      columbinasale, M. columbinum and M. gallinarum) or were not (M. iners and M.
      meleagridis) oxidized, Lysed cells of strains which consumed O2 during glucose or
      organic acid metabolism had relatively high NADH oxidase activity (170-950 nmol
      min-1 mg cell protein-1) and produced 0.02-0.36 mol H2O2 per mol O2 consumed
      during NADH oxidation. In contrast, strains which did not oxidize organic acids
      or consume O2 during glucose or organic acid metabolism possessed low NADH
      oxidase activity (< or = 20 nmol min-1 mg cell protein-1). All arginine
      hydrolysing species showed a high affinity (Km value 1-3 microM) towards
      arginine. The fermentative species similarly showed a high affinity (Km value 2-5
      microM) towards glucose, but used only a small number of additional sugars at
      detectable rates. All M. pullorum strains metabolized sucrose (Km < or = 3
      microM). The type-strains of M. gallisepticum and M. imitans were biochemically
      similar and had high affinities for fructose and mannose. A number of low-passage
      avain isolates, but none of the type strains, metabolized glycerol and, in lysed
      cells, oxidized L-alpha-glycerophosphate (GP) with the production of 1 mol H2O2
      per mol GP.

PMID- 8870192
TI  - Assessment of gelatin gel and elastase tests for detection of protease activity
      of Dichelobacter nodosus isolates from ovine footrot.
AB  - Protease tests (the gelatin gel protease thermostability test, the elastase test
      or both) were performed on 4296 isolates of Dichelobacter nodosus derived from
      452 outbreaks of ovine footrot occurring in New South Wales. Both tests showed a
      high level of repeatability. In the gelatin gel test, culture broths were heated
      for 16 min at 66.8 degrees C. Heated broths containing thermostable protease
      digested gelatin (positive gelatin gel test) while those broths containing
      thermolabile protease failed to digest gelatin (negative gelatin gel test).
      Gelatin gel positive isolates were unable to be graded into subcategories on the
      basis of the percentage stability of their protease. In the elastase test, the
      ability of isolates to digest (positive elastase test) or not digest elastin
      particles (negative test) was measured up to 28 days incubation. Individual
      elastase positive isolates yielded a graded result based on the number of days to
      reach a positive result. There was a very high level of agreement between the
      gelatin gel and the elastase tests consistent with their separating isolates into
      two groups based on protease activity (either gelatin gel positive and elastase
      positive or gelatin gel negative and elastase negative). Either test is suitable
      for use in footrol control and eradication schemes. The gelatin gel test provides
      clearcut separation of isolates into positive and negative categories and has the
      major advantage of yielding a more rapid result than the elastase test. The
      elastase test should be utilised where a graded assessment of protease activity
      is desired.

PMID- 8870193
TI  - Major outer membrane proteins of Pasteurella haemolytica serovars 1-15:
      comparison of separation techniques and surface-exposed proteins on selected
      serovars.
AB  - The Sarkosyl method of obtaining outer membrane proteins (OMPs) from Pasteurella
      haemolytica A1 was more efficient and less laborious than separating membranes by
      sucrose gradient centrifugation. More OMPs were recovered and major OMPs were
      present in greater concentrations in the Sarkosyl-derived preparations.
      Therefore, OMPs of P. haemolytica serovars 1-15 (serovars 3, 4, 10, and 15 being
      T biotypes and the remainder being A biotypes) were prepared by the Sarkosyl
      method and compared by SDS-PAGE. Serovars 1, 2, 5, 6, 7, 8, 11, and 12 which are
      A biovars had similar OMP profiles characterized by major OMPs of 30.5 and 43
      kDa. Biovar T strains were characterized by doublet protein bands in the 26-28
      kDa region and a major OMP in the 38-40 kDa range. Serovars 9, 13, and 14, which
      are also A biovars, had profiles similar, although not identical, to the T
      biovars. A 43 kDa protein was present in all serovars although concentration was
      greater in the A biovars. Surface-exposed proteins of P. haemolytica A1
      determined by 125I-labeling of whole cells were 94, 84, 53.5, 49, 43, 41, 29.5,
      and 16 kDa. Iodine-labeling of serovars A2 and A6 which have similar OMP profiles
      by SDS-PAGE resulted in autoradiographs indistinguishable from A1. These studies
      expand our knowledge of P. haemolytica OMPs especially showing the utility of the
      Sarkosyl extraction procedure, variations in OMP profiles among some A biovar
      strains, and the similarities of OMP profiles and surface-labeled proteins among
      three of the most important serovars (1, 2, and 6).

PMID- 8870194
TI  - Genetic and immunological analyses of a 38 kDa surface-exposed lipoprotein of
      Pasteurella haemolytica A1.
AB  - Pasteurella haemolytica serotype A1 is the bacterial pathogen most frequently
      isolated from the lungs of cattle with bovine respiratory disease. As part of a
      study to characterize P. haemolytica antigens which are important in eliciting
      resistance to pneumonic pasteurellosis, we have cloned and sequenced the gene
      encoding a 38 kDa lipoprotein, Lpp38. The deduced amino acid sequence of Lpp38 is
      similar to those of the Escherichia coli polyamine transport proteins PotD (70%)
      and PotF (33%). P. haemolytica Lpp38 is present in both inner membrane and outer
      membrane fractions of the cell envelope. Susceptibility of Lpp38 to cleavage by
      extracellular proteases indicates that portions of the protein are surface
      exposed. A protein of similar molecular mass in P. haemolytica strains from all
      12 serotypes of biotype A and in an untypeable strain was detected by an anti
      Lpp38 monoclonal antibody. Lpp38 is recognized by sera from calves resistant to
      infection after natural exposure to P. haemolytica and by sera from calves
      protected against infection by vaccination with P. haemolytica A1 outer membranes
      or with live bacteria. These data suggest a role for this protein in the
      development of immunity to P. haemolytica infection.

PMID- 8870195
TI  - Rapid identification of Escherichia coli O157:H7 in bovine feces using the
      antibody-direct epifluorescent filter technique (Ab-DEFT).
AB  - The antibody-direct epifluorescent filter technique (Ab-DEFT) was adapted for
      direct detection of Escherichia coli O157:H7 in bovine feces. The method involved
      suspension of bovine feces in buffer, centrifugation for 30 s, treatment of the
      supernatant with trypsin and Triton X-100 at 50 degrees C for 10 min, pre
      filtration through 5 and 1.2 microns pore filters, and filtration through a 0.4
      micron pore filter. The final filter was stained with fluorescein-labeled
      polyclonal antibody specific for the O157 antigen and examined by epifluorescence
      microscopy. The Ab-DEFT was correlated with viable plate counts for enumeration
      of the pathogen in artificially inoculated bovine feces (r = 0.96). The limit of
      detection was approximately 10(4)-10(5) CFU/g feces. The procedure provided a
      clean background for microscopic visualization of cells; however, cell loss and
      inaccurate quantitation sometimes resulted. E. coli O157:H7 was detected in feces
      of an inoculated calf for more than 3 weeks post-inoculation. The Ab-DEFT may be
      useful for rapid screening of cattle for the presence of the E. coli O157:H7 and
      as an analytical method in ecological studies of the pathogen.

PMID- 8870196
TI  - The development of a ligase mediated PCR with potential for the differentiation
      of serovars within Leptospira interrogans.
AB  - A ligase mediated polymerase chain reaction (LMPCR) was developed to amplify
      between the repetitive element, IS1533, of Leptospira and adjacent chromosomally
      located Bg/II restriction endonuclease enzyme sites. To do this, complimentary
      oligonucleotide linkers designed to anneal together with an overhanging Bg/II end
      were ligated to Bg/II digested DNA from 35 leptospiral reference strains and
      field isolates. This ligated DNA was used as template for PCR with
      oligonucleotide primers specific for the linker and for the repetitive element
      IS1533. The resultant amplicon profile hybridised a 102 bp region derived from
      the terminus of IS1533 thus confirming that amplicons generated by LMPCR
      contained part of IS1533. The number of fragments generated containing IS1533 was
      significantly fewer than that generated by RFLP but the LMPCR method has the
      potential to use far less template DNA and be quicker than standard RFLP. Obvious
      and reproducible interserovar differences were demonstrated by LMPCR whereas for
      20 of 21 L. hardjo-bovis isolates tested no intraserovar differences were
      observed. Of those serovars known to possess IS1533 homologues and tested here by
      LMPCR, each produced a unique amplicon profile which hybridised the IS1533
      terminus probe. The limited heterogeneity amongst hardjo-bovis isolates is
      discussed as is the potential contribution of this method to diagnosis,
      differentiation and the phylogenetics of the Leptospires.

PMID- 8870197
TI  - Vaccination of the badger (Meles meles) against Mycobacterium bovis.
AB  - This review summarizes current knowledge relating to the potential development of
      a vaccine against Mycobacterium bovis (M. bovis) for use in badgers. The serious
      economic loss incurred from bovine tuberculosis in Ireland is highlighted. The
      problems presented to national bovine tuberculosis eradication programmes by
      wildlife reservoirs of M bovis, in particular the badger and the brushtail
      possum, are outlined. Badger and possum ecology and the epidemiology of M. bovis
      infection in these species are compared in relation to control strategies.
      Current information regarding the immune responses of badgers and possums to M.
      bovis infection is presented. Vaccine types, carrier and adjuvant systems,
      available vaccines for human and animal tuberculosis and delivery to wildlife
      species are described. The feasibility of vaccinating badgers against M. bovis
      infection and the possible options for a vaccination strategy are discussed.

PMID- 8870198
TI  - The isolation of recombinant plasmids expressing secreted antigens of Pasteurella
      haemolytica A1 and the characterization of an immunogenic 60 kDa antigen.
AB  - A collection of recombinant plasmids had been isolated which express secreted
      antigens of Pasteurella haemolytica A1 likely to be important in protection. The
      recombinant Escherichia coli clones were found to express the P. haemolytica A1
      antigens by Western immunoblot analysis, using sera from calves which had been
      vaccinated with Presponse and were subsequently resistant to experimental
      challenge with P. haemolytica A1. Detailed analysis of three of the recombinant
      plasmids (pGS1-17, pGS3-19 and pSA1-50) showed that they all carry the same 4.2
      kbp insert DNA. E. coli clones which carry the recombinant plasmids all express a
      strongly antigenic protein of approximately 60 kDa. Nucleotide sequence analysis
      of the cloned DNA showed that it codes for a polypeptide with an estimated M.W.
      of 60.8 kDa. A partial clone of this gene has been reported previously and an
      antibody response to the antigen was shown to be significantly correlated to
      resistance to disease. This gene was found to be present in only the A biotypes
      of P. haemolytica and not in the T biotypes, which have been reclassified
      Pasteurella trehalosi. This demonstrates that this recombinant plasmid collection
      codes for antigens of P. haemolytica A1 important to protection and warrants
      further characterization to identify additional recombinant antigens.

PMID- 8870199
TI  - Biochemical and antigenic relationships between porcine and equine isolates of
      Actinobacillus suis.
AB  - A total of 50 Actinobacillus suis isolates were studied for their biochemical and
      antigenic characteristics. Of them, 40 isolates originated from different tissues
      of diseased pigs, and the other ten isolates were from horses with respiratory
      problems. There was no major biochemical difference among equine and porcine A.
      suis isolates. Results of tube agglutination tests showed that porcines isolates
      were antigenically homogeneous while equine isolates were heterogeneous.

PMID- 8870200
TI  - Causes of mortality and morbidity in exhibition budgerigars in the United
      Kingdom.
AB  - In a survey of the causes of mortality and morbidity in exhibition budgerigars
      from 1984 to 1995, 1525 birds were examined post mortem. Megabacteriosis was the
      most common disease and trichomoniasis, enteritis, pneumonia, hepatitis and a
      degenerative disease of the gizzard lining were also common. A wide variety of
      less common diseases was also found.

PMID- 8870201
TI  - Effect of forage supplements on the incidence of bloat in dairy cows grazing high
      clover pastures.
AB  - The effect of offering forage supplements of different compositions was examined
      in two experiments with cows grazing high clover swards. In the first experiment
      strawmix supplements of high or low energy content (11 and 9 MJ metabolisable
      energy/kg dry matter [DM]) and high or low crude protein content (17 and 4 g/kg
      DM) were offered for periods of three weeks. The energy and protein contents were
      varied by the content of molasses and soyabean meal, respectively. The high
      energy, high protein supplement increased the incidence of bloat, and the low
      energy, high protein supplement reduced it, compared with grazing alone. Bloat
      was most evident in the first two weeks of each feeding period, suggesting that
      the cows partially adapted to the diets within three weeks. In the second
      experiment silage supplements reduced the incidence of bloat among cows grazing
      both tall and short swards. The most suitable forages to feed when there is a
      risk of bloat are those that are slowly fermented in the rumen but are eaten in
      sufficient quantity to reduce periods of rapid herbage intake.

PMID- 8870202
TI  - Osteochondrosis as a cause of lameness in purebred Suffolk lambs.

PMID- 8870203
TI  - Babesia shortti infection in a saker falcon (Falco cherrug).

PMID- 8870204
TI  - Isolation of Yersinia ruckeri from an otter and salmonid fish from adjacent
      freshwater catchments.

PMID- 8870205
TI  - Risk of maternal transmission of BSE.

PMID- 8870206
TI  - Risk of maternal transmission of BSE.

PMID- 8870207
TI  - Risk of maternal transmission of BSE.

PMID- 8870208
TI  - Genetic screening of dogs.

PMID- 8870209
TI  - Foot-and-mouth disease outbreak.

PMID- 8870210
TI  - Helicobacter pylori and stomach ulcers.

PMID- 8870211
TI  - Urethral obstruction in a cat.

PMID- 8870212
TI  - Risk factors for youth victimization: beyond a lifestyles/routine activities
      theory approach.
AB  - Past efforts to understand the risks for youth victimization have primarily
      utilized concepts from lifestyle or routine activity theory, such as the
      increased exposure and reduced guardianship that are entailed when youth engage
      in risky or delinquent behavior. In this article, we argue that other personal
      characteristics put youth at risk, not through any lifestyle or routine activity
      mechanism, but by making certain youth more "congruent" with the needs, motives,
      or reactivities of potential offenders. Three specific types of such
      characteristics are those that increase the potential victim's target
      vulnerability (e.g., physical weakness or psychological distress), target
      gratifiability (e.g., female gender for the crime of sexual assault), or target
      antagonism (e.g., behaviors or ethnic or group identities that may spark
      hostility or resentment). Using data from a national youth survey, we test
      variables measuring such aspects of target congruence and show that they make a
      significant contribution over and above lifestyle variables alone in predicting
      nonfamily, sexual, and parental assault.

PMID- 8870213
TI  - Adjusting to criminal victimization: the correlates of postcrime distress.
AB  - This article explores the correlates of immediate and short-term psychological
      distress among victims of burglary, robbery, and nonsexual assault. A panel
      design was employed. Crime victims were interviewed within 1 month following the
      incident and again 3 months later. Four sets of predictors were examined:
      demographics, previctimization adjustment and stress, features of the crime
      incident, and victims' perceptions. Measures of distress included a range of
      standard indices of adjustment and symptomatology. Demographic characteristics
      and victim perceptions accounted for the greatest proportions of variance in the
      outcome measures at Time 1 and Time 2. The strongest predictors of psychological
      adjustment at the end of 3 months included adjustment after 1 month, education,
      victim injury, victims' beliefs that their lives had been endangered during the
      crime episode, and victims' appraisals of the world as meaningful. Implications
      for treatment and directions for future studies are discussed.

PMID- 8870214
TI  - Self-reported sexual interest in children: sex differences and psychosocial
      correlates in a university sample.
AB  - A sample of 180 female and 99 male university students were surveyed regarding
      their sexual interest in children. Males reported sexual attraction to at least
      one child more often than did females (n = 22 [22.2%] and n = 5 [2.8%],
      respectively). Both males and females reported very low rates of sexual fantasies
      about children, masturbation to such fantasies, or potential likelihood of sexual
      contact with a child. Males' sexual attraction to children was associated with
      lower self-esteem, greater sexual conflicts, more sexual impulsivity, lower
      scores on the Socialization scale of the California Psychological Inventory,
      greater use of pornography depicting consenting adult sex, and more self-reported
      difficulty attracting age-appropriate sexual partners. Childhood victimization
      history and attitudes supporting sexual aggression did not discriminate self
      reported sexual attraction to children.

PMID- 8870215
TI  - Attrition from a male batterer treatment program: client-treatment congruence and
      lifestyle instability.
AB  - Although patient compliance is a problem for almost all forms of therapy,
      treatment programs for male batterers face special concerns. Male batterers are
      often perceived as coming to therapy only because of the external pressures of
      courts or intimate partners. In the present study, we examined the rates at which
      male batterers failed to attend treatment following an initial assessment
      interview. Of the 526 men recommended for treatment, only 218 (41%) attended a
      single treatment session, and only 132 (25%) completed the brief (10-week)
      treatment program. The variables associated with attrition fell into two general
      categories: (a) those associated with lifestyle instability (e.g., moves,
      unemployment, youthfulness), and (b) those variables indicating a congruence
      between the clients' self-identified problems and the targets of treatment (e.g.,
      self-admitted problems with spousal assault). Suggestions are provided as to how
      programs could reduce their attrition rates by attending to the issues of client
      treatment congruence and lifestyle instability.

PMID- 8870216
TI  - Conducting research on child maltreatment: effects on researchers.
AB  - This report discusses the potential negative psychological consequences of
      conducting child maltreatment research on the researchers themselves.
      Illustrations of these effects are drawn from the experiences of a study of child
      maltreatment. Common themes of anger, sadness, frustration, and powerlessness
      emerged as reactions to reviewing case records of child maltreatment. Just as
      study protocols must include procedures for protecting the subjects of research,
      so they should include methods for helping the researchers cope with emotional
      distress brought about by their work. Several strategies are suggested for
      ensuring that research staff receive sufficient support to minimize the negative
      effects of conducting research on sensitive topics.

PMID- 8870217
TI  - Protecting child witnesses: judicial efforts to minimize trauma and reduce
      evidentiary barriers.
AB  - Growing attention has been given to the need to protect child witnesses from the
      potential trauma associated with providing testimony in the courtroom, as well as
      to the importance of maximizing the validity and reliability of that testimony.
      At the same time, these efforts may conflict with the right of an accused to
      confront his or her accuser or various evidentiary rights of the accused.
      Numerous educational programs have been conducted to assist judges and lawyers to
      better respond to these issues. A nation-wide survey of judges was conducted to
      determine the relative use of various means to minimize trauma or reduce
      evidentiary barriers in child sexual abuse cases, how judges evaluate these
      means, and the impact of educational programs in this area. The survey indicated
      that although judges use a broad range of approaches to minimize this trauma or
      reduce evidentiary barriers, they are particularly likely to use simpler
      techniques that are relatively easy to implement and which they consider both
      effective and fair to the parties appearing before the court. Attending
      educational programs appears to influence the use of these approaches. Survey
      results also indicated the best methods for disseminating relevant information on
      child sexual abuse to judges.

PMID- 8870218
TI  - Response properties of long-range axon-bearing amacrine cells in the dark-adapted
      rabbit retina.
AB  - Axon-bearing amacrine cells in mammalian retinae are encountered relatively
      infrequently during electrophysiological investigations, and thus very little is
      known about their physiological properties. Patch-clamp electrodes were used to
      record light responses from two axon-bearing amacrine cells in flat-mounted, dark
      adapted rabbit retina. The recorded cells were stained, and the morphology
      visualized. Both cells were capable of generating action potentials. In one case,
      a linear relationship between mean depolarization and action-potential frequency
      was demonstrated. The cells had a proximal dendritic arbor and a morphologically
      distinct, much larger axon terminal system. The receptive field of the center
      response was coextensive with the dendritic arbor, and thus also much smaller
      than the axon terminal system. The center response was suppressed by activation
      of an inhibitory surround. Both cells responded to center illumination with an
      inward current which became more transient as the size of the illuminating spot
      was increased. It is suggested that axon-bearing amacrine cells receive input
      over a receptive field defined by the dendritic arbor, and distribute their
      output over a much more extensive axon terminal system, most probably via action
      potentials.

PMID- 8870219
TI  - Adaptation of visually evoked responses of relay cells in the dorsal lateral
      geniculate nucleus of the cat following prolonged exposure to drifting gratings.
AB  - Adaptation of visual cortical cells' responses is observed following repeated
      presentation of grating stimuli. Grating adaptation is believed to exist only at
      the cortical level. The purpose of this study was to see if grating adaptation
      also occurs in the lateral geniculate nucleus. We studied the responses of 164
      relay cells in layer A and A1 of the dorsal lateral geniculate nucleus (LGNd) to
      grating stimuli. Normal cats, as well as cats in which visual cortex was ablated,
      were studied. Adaptation was investigated using repeated presentation of gratings
      of different contrasts and orientations. The results showed the following: (1)
      Grating adaptation reduced the responses of 46% of the LGNd cells recorded. The
      responses normally decreased within 30 s and then stabilized. However, there was
      heterogeneity in the effects observed. About 38% of the cells studied were not
      affected by the adapting gratings. Some cells (16%) showed facilitation rather
      than habituation of their responses to test stimuli. (2) There was no significant
      difference between X and Y cells in their susceptibility to adaptation. This
      suggests that grating adaptation is a general property, independent of cell type.
      (3) The contrast-response curves of 57% of the LGNd cells studied shifted down
      after exposure to high-contrast adapting gratings. (4) Adapting gratings of the
      cells' preferred orientation decreased the orientation sensitivity of 56% of the
      orientation-sensitive cells. Adapting gratings at the nonpreferred orientation
      did not affect orientation sensitivity. (5) Prolonged grating adaptation also
      reduced the responses of 49% of the LGNd cells after inactivation of cortical
      inputs to the LGNd.

PMID- 8870220
TI  - Monocular mechanisms determine plaid motion coherence.
AB  - Although the neural location of the plaid motion coherence process is not
      precisely known, the middle temporal (MT) cortical area has been proposed as a
      likely candidate. This claim rests largely on the neurophysiological findings
      showing that in response to plaid stimuli, a subgroup of cells in area MT
      responds to the pattern direction, whereas cells in area V1 respond only to the
      directions of the component gratings. In Experiment 1, we report that the
      coherent motion of a plaid pattern can be completely abolished following
      adaptation to a grating which moves in the plaid direction and has the same
      spatial period as the plaid features (the so-called "blobs"). Interestingly, we
      find this phenomenon is monocular: monocular adaptation destroys plaid coherence
      in the exposed eye but leaves it unaffected in the other eye. Experiment 2
      demonstrates that adaptation to a purely binocular (dichoptic) grating does not
      affect perceived plaid coherence. These data suggest several conclusions: (1)
      that the mechanism determining plaid coherence responds to the motion of plaid
      features, (2) that the coherence mechanism is monocular, and thus (3), that it is
      probably located at a relatively low level in the visual system and peripherally
      to the binocular mechanisms commonly presumed to underlie two-dimensional (2-D)
      motion perception. Experiment 3 examines the spatial tuning of the monocular
      coherence mechanism and our results suggest it is broadly tuned with a preference
      for lower spatial frequencies. In Experiment 4, we examine whether perceived
      plaid direction is determined by the motion of the grating components or the
      features. Our data strongly support a feature-based model.

PMID- 8870221
TI  - Overrepresentation of the central visual field in the superior colliculus of the
      pigmented and albino ferret.
AB  - We have examined the retinotopy in the superior colliculus of pigmented and
      albino ferrets using both anatomical and electrophysiological methods. While the
      distribution of contralaterally projecting retinotectal ganglion cells is
      characterized by the presence of an area centralis superimposed on a visual
      streak in both strains, the ipsilateral projection from temporal hemiretina is
      strongly reduced in albinos. In spite of the significantly altered retinotectal
      projection pattern, the collicular visual field map in the albino ferret reveals
      the same characteristics as in the pigmented animal with a strongly enlarged
      representation of the center of visual space. An areal comparison between
      retinotectal ganglion cell distribution and collicular areal magnification shows
      that the increase in areal magnification factor between the periphery and the
      representation of the central visual hemifield exceeds the corresponding increase
      in retinal ganglion cell density between peripheral retina and area centralis by
      a factor of three in pigmented and a factor of four in albino ferrets. The areal
      magnification factor of the representation of the retinal visual streak does not
      exceed the increase in retinotectal ganglion cell density. Thus, our results
      suggest that the representation of visual space in the superior colliculus of
      albino and pigmented ferrets does not simply follow the retinotectal ganglion
      cell density, but that there is an enhanced representation of the frontal central
      visual field. The possibility is discussed that the collicular visual field map
      may be determined either by both retinotectal and corticotectal projections or by
      the colliculus' intrinsic structure.

PMID- 8870222
TI  - Amplitude and phase variations of harmonic components in human achromatic and
      chromatic visual evoked potentials.
AB  - Occipital visual evoked potentials (VEPs) were recorded in response to low
      contrast, low spatial-frequency chromatic, and achromatic gratings. Fast Fourier
      Transform (FFT) and time-domain analysis were used to reveal differences in
      harmonic content and amplitude of chromatic and achromatic response components
      over a wide range of temporal frequencies. The chromatic ON/OFF VEP is dominated
      by the fundamental component indicating that onset and offset responses are
      different. This type of response is typical of neurons with sustained type
      response characteristics. Conversely, the achromatic onset VEP contains a
      predominant second harmonic component in addition to the fundamental. This
      similarity between onset and offset responses suggests that transient mechanisms
      are responsible for the generation of achromatic components. Frequency analysis
      of VEPs elicited by phase-reversing stimuli reveals that all of the response
      energy is concentrated at the second harmonic of the stimulating frequency. The
      magnitude of the second harmonic component is maximal for achromatic stimuli and
      undergoes a distinct minimum for isoluminant, chromatic stimuli. This behavior
      indicates that under the stimulus conditions used, magnocellular neurons with
      transient characteristics dominate the reversal VEP.

PMID- 8870223
TI  - Central neural circuits for the light-mediated reflexive control of choroidal
      blood flow in the pigeon eye: a laser Doppler study.
AB  - Electrical stimulation in pigeons of the input from the medial subdivision of the
      nucleus of Edinger-Westphal (EWM) to the choroidal neurons of the ipsilateral
      ciliary ganglion, which themselves have input to the choroidal blood vessels of
      the ipsilateral eye, increases choroidal blood flow (ChBF). Since the EWM
      receives input from the contralateral suprachiasmatic nucleus (SCN), which in
      turn receives contralateral retinal input, the present study sought to determine
      if activation of the SCN by microstimulation or by retinal illumination of the
      contralateral eye would also yield increases in ChBF in that same eye. Using
      laser Doppler flowmetry (LDF) to measure ChBF, we found that electrical
      activation of the contralateral SCN by 100-Hz anodal pulse trains yielded
      increases in ChBF that were stimulus related and proportional to the stimulating
      current. These increases in ChBF elicited by the SCN stimulation were accompanied
      by increases in choroidal volume (vasodilation), but not by increases in systemic
      blood pressure. Furthermore, the increases could be blocked reversibly by
      lidocaine injection into the EWM. These results suggest that the increases in
      ChBF in the eye contralateral to the SCN stimulation were specifically mediated
      by the SCN-EWM pathway. Retinal illumination with a fiber optic light source was
      also found to increase ChBF in the illuminated eye, and these effects too could
      be blocked reversibly with lidocaine injection into the EWM or permanently by the
      EWM lesion. Control studies confirmed that the light-elicited increases were
      mediated by increases in choroidal volume (i.e. vasodilation), were not
      accompanied by systemic blood pressure increases, and were not artifactually
      generated by transocular illumination of the LDF probe. Thus, the SCN-EWM circuit
      may be involved in regulating ChBF in response to the level of retinal
      illumination and/or the visual patterns falling on the retina.

PMID- 8870224
TI  - Microglia in the nerve fiber layer of the cat retina: detection of postnatal
      changes by a new monoclonal antibody.
AB  - This paper describes changes in the appearance and distribution of microglia in
      postnatal cat retina as demonstrated by a new antibody, H386F. This fractionated
      IgM antibody was created via an intrasplenic immunization of a single BALB/C
      mouse with about 2-3 x 10(5) large, whole cells isolated from 46 minced cat
      retinae. To confirm that the labeled cells are microglia, the staining properties
      of H386F were compared with those of four commercially available antibodies, OX
      33, OX-41, OX-42, and ED-1, that have been used by others to distinguish between
      microglia and other cells in rat brain. These experiments show that H386F is the
      only antibody of the five to label only microglia in both the cat retina and
      hippocampus.

PMID- 8870225
TI  - Corticofugal influences on visual responses in cat superior colliculus: the role
      of NMDA receptors.
AB  - The role of N-methyl-D-aspartate (NMDA) receptors in the mediation of cortical
      inputs to visual neurones in the superficial layers of the superior colliculus
      (SSC) has been investigated. Extracellular recording with iontophoresis in the
      SSC of cortically intact cats has demonstrated that visual responses of most
      neurones were reduced by iontophoretic application of the NMDA receptor
      antagonist D-2-amino-5-phosphonopentanoate (AP5). Following inactivation of areas
      17 and 18 of the visual cortex with topical lignocaine, the visual responses of
      11, previously AP5-sensitive, neurones were no longer reduced by AP5 ejection.
      The cortical input is generally assumed to influence the directional responses of
      visual neurones in SSC. However, detailed study of the directional bias showed
      that the degree of directional tuning in SSC neurones was similar to that of
      retinal ganglion cells, as previously described by others. Moreover, inactivation
      of the visual cortex with topical lignocaine did not alter the directional bias
      of SSC neurones. Likewise, the directional bias of SSC neurones was not reduced
      by iontophoretic ejection of AP5 in the SSC. These data imply that NMDA receptors
      have an important role in mediating the cortical input to the SSC. However,
      cortical input does not appear to be responsible for conferring directional bias
      upon SSC neurones' visual responsiveness.

PMID- 8870226
TI  - Ontogeny of preproenkephalin mRNA expression in the rat retina.
AB  - Endogenous opioid systems (i.e. opioid peptides and opioid receptors) modulate
      developmental events in the neonatal mammalian retina. In the present study, the
      mRNA encoding preproenkephalin A (PPE), the prohormone for the opioid growth
      factor (OGF), [Met5]-enkephalin, was studied in the developing and the adult
      retinas of rats. Northern analysis indicated the presence of a 1.4-kb message in
      the developing and adult retinas corresponding to rat PPE mRNA. Quantitation
      showed that PPE message was present on postnatal day 1 at 5% of the adult level,
      and increased during development until the adult quantity was reached by
      postnatal day 27. In situ hybridization experiments first detected the presence
      of PPE mRNA in retinal tissues during late gestation. In late prenatal and
      neonatal retinas, PPE message was associated with areas of the developing retina
      containing proliferating neuroblasts and postmitotic cells. Later in development,
      message appeared to be located primarily within the inner retina, with abundant
      PPE mRNA associated with putative horizontal cells of the inner nuclear layer
      (INL). The adult retina showed a similar pattern of PPE gene expression in the
      cells of the INL. These findings document that the gene expression in the retina
      for PPE begins in the fetus, continues during retinal development, and coincides
      with the presence of a PPE mRNA derivative ([Met5]-enkephalin) that regulates DNA
      synthesis during retinal ontogeny. Our results are also the first to show the
      presence of PPE message in the adult mammalian retina, suggesting transcription
      of an opioid gene in the mature visual system.

PMID- 8870227
TI  - Potassium-evoked directionally selective responses from rabbit retinal ganglion
      cells.
AB  - Previous studies have shown that directionally selective (DS) retinal ganglion
      cells cannot only discriminate the direction of a moving object but they can also
      discriminate the sequence of two flashes of light at neighboring locations in the
      visual field: that is, the cells elicit a DS response to both real and apparent
      motion. This study examines whether a DS response can be elicited in DS ganglion
      cells by simply stimulating two neighboring areas of the retina with high
      external K+. Extracellular recordings were made from ON-OFF DS ganglion cells in
      superfused rabbit retinas, and the responses of these cells to focal applications
      of 100 mM KCl to the vitreal surface of the retina were measured. All cells
      produced a burst of spikes (typically lasting 50-200 ms) when a short pulse (10
      50 ms duration) of KCl was ejected from the tip of a micropipette that was placed
      within the cell's receptive field. When KCl was ejected successively from the
      tips of two micropipettes that were aligned along the preferred-null axis of a
      cell, sequence-dependent responses were observed. The response to the second
      micropipette was suppressed when mimicking motion in the cell's null direction,
      whereas an enhancement during apparent motion in the opposite direction
      frequently occurred. Sequence discrimination in these cells was eliminated by the
      GABA antagonist picrotoxin and by the Ca(2+)-channel blocker omega-conotoxin
      MVIIC, two drugs that are known to abolish directional selectivity in these
      ganglion cells. The spatiotemporal properties of the K(+)-evoked sequence
      dependent responses are described and compared with previous findings on apparent
      motion responses of ON-OFF DS ganglion cells.

PMID- 8870228
TI  - Factors controlling the dendritic arborization of retinal ganglion cells.
AB  - The effects of changing retinal ganglion cell (RGC) density and availability of
      presynaptic sites on the development of RGC dendritic arbor in the developing
      chick retina were contrasted. Visual form deprivation was used to induce ocular
      enlargement and expanded retinal area resulting in a 20-30% decrease in RGC
      density. In these retinas, RGC dendritic arbors increased in a compensatory
      manner to maintain the inner nuclear layer to RGC convergence ratio in a way that
      is consistent with simple stretching; RGC dendritic arbors become larger with
      increased branch lengths, but without change in the total number of branches. In
      the second manipulation, partial optic nerve section was used to produce areas of
      RGC depletion of approximately 60% in the central retina. This reduction in
      density is comparable to the density of locations in the normal peripheral
      retina. In RGC depleted retinas, dendritic arbor areas of RGCs in the central
      retina grow to match the size of normal peripheral arbors. In contrast to the
      expanded case, two measures of intrinsic arbor structure are changed in RGC
      depleted retinas; the branch density of RGC dendrites is greater, and the
      relative areas of the two arbors of bistratified cells are altered. We discuss
      the potential roles of retinal growth, local RGC density, and availability of
      presynaptic terminals in the developmental control of RGC dendritic arbor.

PMID- 8870229
TI  - The horizontal cells of artiodactyl retinae: a comparison with Cajal's
      descriptions.
AB  - The morphology of horizontal cells in ox, sheep, and pig retinae as observed
      after Lucifer Yellow injections are described and compared with the descriptions
      of Golgi-stained cells by Ramon y Cajal (1893). Horizontal cells in the retinae
      of less domesticated species, wild pig, fallow and sika deer, mouflon, and
      aurochs were also examined. All these retinae have two types of horizontal cell;
      their morphologies are in common, although with some familial differences. Their
      basic appearance is as Cajal described; except in one important respect, a single
      axon-like process could not be identified on the external horizontal cells. It is
      concluded that external horizontal cells of artiodactyls correspond to the
      axonless (A-type) cells of other mammals. Cajal's internal horizontal cells have
      a single axon which contacts rods. This type corresponds to the B-type cells of
      other mammalian retinae. Artiodactyl A- and B-type horizontal cells differ from
      those of many other mammals in that the B-type dendritic tree is robust and the A
      type dendritic tree is delicate. Historically, this morphological difference
      between orders of mammals has led to some confusion. The comparisons presented
      here suggest that the morphological types of primate horizontal cells can be
      integrated into a general mammalian classification.

PMID- 8870230
TI  - An in vitro study of retinotectal transmission in the chick: role of glutamate
      and GABA in evoked field potentials.
AB  - We have developed two brain slice preparations for studying tectofugal visual
      pathways in the chick: conventional, 400-microns slices ("thin slices"), and
      "thick slices" which encompass the rostral pole of the optic tectum and the
      contralateral optic nerve. Stimulation was delivered with a bipolar electrode
      positioned in stratum opticum in thin slices and in the contralateral optic nerve
      in thick slices. While the latter preparation provided a means of exclusively and
      unambiguously activating retinal afferents, several lines of evidence also
      indicated that the evoked field potentials in thin slices were chiefly consequent
      to retinal afferent excitation: (1) the similarity of evoked field potentials in
      thin slices to those in thick slice preparations; (2) their precise localization
      in retinorecipient layers as shown by prelabeling from retina with FITC-coupled
      cholera toxin; (3) transmission delays appropriate for retinal afferents as
      established with the thick slice preparation; (4) patterns of labeled afferents
      resulting from applications of Dil crystals to slices fixed after recording; and
      (5) the similarity in transmitter pharmacology between thin and thick slice
      preparations. Pharmacological manipulations carried out with bath-applied
      antagonists indicated that glutamate is the principal retinotectal transmitter.
      The broadly active glutamate receptor blocker, kynurenic acid, reversibly
      eliminated the postsynaptic component of the field potential as confirmed with 0
      Ca2+ saline. A complete block was also effected by the non-NMDA antagonists CNQX
      and DNQX. The specific NMDA antagonist, AP5, caused a smaller and variable
      reduction in response amplitude. The GABA antagonist, bicuculline, caused a
      prolongation of the monosynaptic field epsp in retinorecipient layers and an
      enhancement of the long-latency, negative wave in cellular layers below,
      supporting a late, excitation-limiting role for this inhibitory transmitter.

PMID- 8870231
TI  - Synaptic organization of an organotypic slice culture of the mammalian retina.
AB  - Vertical slices of postnatal day 6 (P6) rat retina were cut and cultured using
      the roller-tube technique. The organotypic differentiation during a culture
      period of up to 30 days has been described in a previous study (Feigenspan et
      al., 1993a). Here we concentrated on the synaptic organization in the retinal
      slice culture. Electron microscopy revealed the presence of ribbon synapses in
      the outer plexiform layer and conventional and ribbon synapses in the inner
      plexiform layer. Immunofluorescence with antibodies that recognize specific
      subunits of GABAA or glycine receptors revealed a punctate distribution of the
      receptors. They were aggregated in "hot spots" that correspond to a concentration
      of receptors at postsynaptic sites. Different isoforms of GABAA and glycine
      receptors occurred in the slice cultures. The experiments show that there is a
      differentiation of synapses and a diversity of transmitter receptors in the slice
      cultures that is comparable to the in vivo retina.

PMID- 8870232
TI  - Soma and axon diameter distributions and central projections of ferret retinal
      ganglion cells.
AB  - Using a combination of retrograde horseradish peroxidase (HRP) labelling, silver
      staining, and electron microscopy, we have assessed the relationship between
      retinal ganglion cell soma size and axon diameter in the adult ferret (Mustela
      putorius furo). Retinal ganglion cells were labelled following injections of HRP
      into the lateral geniculate nucleus (LGN), superior colliculus (SC), or LGN+SC.
      The soma size distributions following LGN, SC, or LGN+SC injections were all
      unimodal showing considerable overlap between different cell classes. This was
      confirmed for alpha cells identified on the basis of dendritic filling or from
      neurofibrillar-stained retinae. Analysis of the soma size and axon diameters of a
      population of heavily labelled retinal ganglion cells showed a significant
      correlation between the two. However, the overall distribution of intraretinal
      axon diameter was bimodal with an extended tail. Analysis of the ganglion cell
      distributions in the adult ferret indicates that beta cells comprise about 50.5
      55%, gamma 42.5-47%, and alpha 2.5% of the ganglion cell population. This implies
      that the proportion of gamma, beta, alpha cells in both cat and ferret retina is
      highly conserved despite differences in visual specialization in the two species.

PMID- 8870233
TI  - Pattern of ocular dominance columns in human striate cortex in strabismic
      amblyopia.
AB  - Previous experiments in animals have shown that early unilateral eyelid suture, a
      model of amblyopia induced by cataract, causes shrinkage of ocular dominance
      columns serving the deprived eye in the striate cortex. It is unknown whether the
      ocular dominance columns are affected in amblyopia produced by strabismus. We
      examined specimens of striate cortex obtained postmortem from a 79-year-old woman
      with a history of amblyopia in her left eye (20/800) since age 2 from
      accommodative esotropia. Four years prior to her death, she suffered an ischemic
      infarct of the left optic disc. This injury to the left optic disc made it
      possible to label the ocular dominance columns using cytochrome oxidase
      histochemistry. The pattern of ocular dominance columns was reconstructed
      throughout most of the right striate cortex. No shrinkage of columns was found.
      In the left cortex only half the column mosaic was labelled, because the patient
      had some residual vision in the temporal retina of her left eye. The columns
      within the labelled portion of the overall mosaic appeared normal. These findings
      indicate that shrinkage of ocular dominance columns does not occur in humans with
      amblyopia caused by accommodative esotropia. The ocular dominance columns are
      probably no longer susceptible to shrinkage at the age when most children with
      this condition begin to develop amblyopia.

PMID- 8870234
TI  - Neural responses to velocity gradients in macaque cortical area MT.
AB  - Visual motion, i.e. the pattern of changes on the retinae caused by the motion of
      objects or the observer through the environment, contains important cues for the
      accurate perception of the three-dimensional layout of the visual scene. In this
      study, we investigate if neurons in the visual system, specifically in area MT of
      the macaque monkey, are able to differentiate between various velocity gradients.
      Our stimuli were random dot patterns designed to eliminate stimulus variables
      other than the orientation of a velocity gradient. We develop a stimulus space
      ("deformation space") that allows us to easily parameterize our stimuli. We
      demonstrate that a substantial proportion of MT cells show tuned responses to our
      various velocity gradients, often exceeding the response evoked by an optimized
      flat velocity profile. This suggests that MT cells are able to represent complex
      aspects of the visual environment and that their properties make them well suited
      as building blocks for the complex receptive field properties encountered in
      higher areas, such as area MST to which many cells in area MT project.

PMID- 8870235
TI  - The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion
      exchange chromatography.
AB  - The introduction of high pH anion-exchange chromatography (HPAEC) has represented
      a major development in the qualitative analysis of glycoprotein derived
      oligosaccharides. When coupled with pulsed amperometric detection, the technique
      permits the detection of picomole quantities of heterogeneous mixtures of
      oligosaccharide without the need for derivatisation. The applications of HPAEC
      have generally been limited to the analysis of sialylated oligosaccharides,
      however, it is now possible to analyse heterogenous mixtures of neutral
      oligosaccharides with the latest systems. We have used such a system to separate
      completely a panel of seven commercially available neutral N-linked
      oligosaccharides and found the influence of monosaccharide substitution on
      elution position to be identical to that for sialylated structures. A standard
      monosialylated N-linked oligosaccharide was modified by sequential digestion with
      specific exoglycosidases to produce a monogalactosylated, diantennary
      oligosaccharide which is commercially unavailable. This standard's elution
      position was confirmed by HPAEC. The technique was applied to the identification
      of neutral N-linked oligosaccharides released from human immunoglobulin G using
      the enzyme peptide-N-glycosidase F.

PMID- 8870236
TI  - Synthesis of glycolipids containing disaccharides and two longer alkyl chains and
      their applications as enzyme modifiers.
AB  - The aminolysis between p-(aminomethyl)benzoic acid and lactobiono-1,5-lactone was
      carried out in Me2SO in quantitative yield. The amide formed thus was used
      directly for the final reaction without isolation of the intermediate from the
      reaction mixture. This simple one-pot procedure finished a convenient and useful
      synthesis of the target N-[p-(dialkyl-L-glutamatecarbonyl)
      benzyl]lactobionamides. The phase-transition temperature of glycolipids was shown
      to greatly depend on the structure between the hydrophilic moiety and the
      hydrophobic segment of the glycolipids. The yield of proteins of lipases coated
      with the glycolipids containing disaccharides remarkably increased with alkyl
      chain length, which was higher than that with glycolipids containing
      monosaccharides. The yields were also closely correlated to the origin of the
      lipases. The enzymatic reactivity of lipid-coated lipase PS was seldom affected
      by the hydrophobic segment of lipids, but its enantioselectivity was mainly
      affected by the hydrophilic moiety of lipids.

PMID- 8870237
TI  - Transglycosylation of intact sialo complex-type oligosaccharides to the N
      acetylglucosamine moieties of glycopeptides by Mucor hiemalis endo-beta-N
      acetylglucosaminidase.
AB  - The endo-beta-N-acetylglucosaminidase (endo-beta-GlcNAc-ase) of Mucor hiemalis,
      endo-M, was found to transfer the sialo complex-type oligosaccharides from
      transferrin glycopeptide to the N-acetylglucosamine (GlcNAc) moieties of peptidyl
      GlcNAc. Disialo complex-type oligosaccharide of transferrin glycopeptide was
      transferred to 9-fluorenylmethyloxycarbonyl (Fmoc)-asparaginyl-N
      acetylglucosaminide (Fmoc-Asn-GlcNAc) by endo-M in a high yield. The structure of
      the reaction product was confirmed to be Fmoc-Asn-(GlcNAc)2-Man-(Man-GlcNac-Gal
      NeuAc)2 by mass spectrometry. Endo-M also transferred disialo complex-type
      oligosaccharide to the GlcNAc residue of chemically synthesized H-Ile-Asn(GlcNAc)
      Ala-Thr-Leu-OH. Asn-linked asialo complex-type oligosaccharide and Asn-linked
      high-mannose type oligosaccharide were also effective as oligosaccharide donors.
      Transfer of disialo complex-type oligosaccharide to the GlcNAc-peptide was the
      most effective among the three types of oligosaccharides, although the disialo
      complex-type oligosaccharide attached to the peptide was the poorest substrate
      for the hydrolytic activity of endo-M.

PMID- 8870238
TI  - Solid-phase synthesis of an O-linked glycopeptide based on a benzyl-protected
      glycan approach.
AB  - The solid-phase synthesis of asialo-[Ala18]-B-chain (2) of human alpha 2HS
      glycoprotein is described. Disaccharide-linked serine unit 12, carrying a benzyl
      protecting group, was synthesized via stereoselective glycosylation of 8 with 6.
      Peptide synthesis was carried out by the Fmoc method utilizing an automated
      peptide synthesizer. A modified procedure using a mechanical shaker at the
      coupling step with 12 made easy the recovery of unreacted 12. The benzylated
      glycopeptide thus synthesized was cleaved from the resin and hydrogenated to give
      2.

PMID- 8870239
TI  - Synthesis of inositol 2-phosphate-quercetin conjugates.
AB  - The antiproliferative flavonoid, quercetin, is limited in its pharmacological
      utility by its low water solubility. In this paper, we describe the synthesis of
      two quercetin analogues prepared by linking the hydroxyl group at the 3- or 5
      position of the flavonoid to the 1-hydroxyl group of myo-inositol-2-phosphate via
      a succinate diester linkage. The resulting conjugates were found to have
      dramatically enhanced water solubility relative to quercetin; the 5-linked
      quercetin analogue 2 had a water solubility of > 300 mg/mL at 20 degrees C.
      Comparison of the in vitro cytotoxicity and antiproliferative activity of
      conjugate 2 with those of quercetin toward cultured human colon adenocarcinoma
      (SW480) and human glioblastoma (U87MG) cells indicated that this modification of
      quercetin does not significantly diminish its activity in these assays.

PMID- 8870240
TI  - N1-alkyl-D-gluconamidines: are they 'perfect' mimics of the first transition
      state of glucosidase action?
AB  - The inhibition of four beta-glucosidases of plant, fungal, and mammalian origin
      by N1-butyl- and N1-dodecyl-D-gluconamidine was determined. Comparison with the
      inhibition by the corresponding N-alkyl-D-glucosylamines revealed that the
      strongly basic amidines (pKa 10.8) were at the most 10-times more inhibitory than
      the weakly basic glucosylamines (pKa 6.5). The small enhancement of inhibitory
      potency, resulting from transforming the tetrahedral C-1 geometry of the
      glucosylamines to the planar sp2-geometry of the amidines, was ascribed to the
      inability of the fully protonated amidines to function as hydrogen bond acceptors
      with the catalytic acid of the enzyme. Additional evidence for the importance of
      a hydrogen bond for strong inhibition came from the comparison of K1-values of
      the weakly basic 5-amino-5-deoxyhexopyranoses and 1,5-iminohexitols with those of
      the corresponding glyconamidrazones (pKa 8.4), which also have a planar C-1
      geometry but are largely protonated under the assay conditions and which had
      similar or up to 10(4)-times larger K1-values than the former. Transition state
      resemblance was judged from the ratio KS(alkyl beta-glucoside)/K1(alkyl
      gluconamidine) relative to the rate acceleration factor kcat/kuncat (Wolfenden,
      Acc, Chem. Res., 5 (1972) 10-16). Compared to ratios of kcat/kuncat from > or =
      10(11) to > or = 10(13), the ratios for KS/K1 were only from 10(3) to 2 x 10(4)
      except for beta-glucosidase A3 from Asp. wentii which had KS/K1 2.8 x 10(6). This
      enzyme differs from the others by being strongly inhibited by cationic glycon and
      substrate analogues rather than by basic ones. The pH-dependence of 1/K1 and the
      'slow' approach to the inhibition is discussed with respect to transition state
      resemblance.

PMID- 8870241
TI  - Structural studies of the O-specific chain of Hafnia alvei strain 32
      lipopolysaccharide.
AB  - The structure of the O-specific side chain of the Hafnia alvei strain 32
      lipopolysaccharide has been investigated. Methylation analysis, partial acid
      hydrolysis, Smith degradations, NMR spectroscopy, MALDI-TOF and FAB mass
      spectrometry in combination with collision-induced decomposition MS/MS were the
      principal methods used. It is concluded that the polysaccharide is composed of
      pentasaccharide repeating units having the following structure which is partially
      O-acetylated in the 2- (20%) and 3- (50%) position of the-->4)-alpha-D-GalpA-(1-
      >residue. [sequence :see text] A MALDI-TOF mass spectrum of the O-specific chains
      indicated that they consisted of up to 16 repeating units.

PMID- 8870243
TI  - The synthesis of galactopyranosyl derivatives with beta-galactosidases of
      different origins.
AB  - beta-Galactosidases from four different sources were used to catalyze the
      transfer of beta-D-galactopyranosyl from 4-nitrophenyl-beta-D-galactopyranoside
      to a hydroxyl group of 2-acetamido-2-deoxy-galactopyranose in the synthesis of
      Gal beta (1-3)GalNAc (1), Gal beta (1-4)GalNAc (2) and Gal beta (1-6)GalNAc (3),
      in triethyl phosphate buffered solutions (20-60%). When beta-galactosidases from
      Penicillium multicolor and Aspergillus oryzae were used as the catalysts, the
      beta (1-6)-linked disaccharide was produced as the major product. However, with
      beta-galactosidase from Bifidobacterium bifidum, the major products were the beta
      (1-4) and beta (1-6)-linked disaccharides. On the other hand, with beta
      galactosidase from Streptococcus 6646K, beta (1-3)-linked disaccharide was
      predominant together with beta (1-4)-linked isomer. Gal beta (1-3)GlcNAc (4), Gal
      beta (1-4)GlcNAc (5) and Gal beta (1-6)GlcNAc (6) were also synthesized with beta
      galactosidase from S. 6646K and B. bifidum with 2-acetamido-2-deoxy-glucopyranose
      as the acceptor and PNPGal as the donor. In both cases, the beta (1-4)-linked
      disaccharide was predominantly produced. In addition, a comparative study was
      carried out to determine the regioselectivity of the transglycosylation reaction
      as well as the hydrolytic specificity toward the same linked disaccharides.

PMID- 8870244
TI  - NMR characterization of a 4-O-methyl-beta-D-glucuronic acid-containing
      rhamnogalacturonan from yellow mustard (Sinapis alba L.) mucilage.

PMID- 8870245
TI  - Bartonella bacilliformis: dangerous pathogen slowly emerging from deep
      background.
AB  - Bartonella bacilliformis was perhaps the most lethal bacterial human pathogen in
      the pre-antibiotic era, but infections were and are limited to a specific
      geographical area, largely in Peru, corresponding to the range of its sand fly
      vector. B. bacilliformis targets both red cells and endothelial cells. Recent
      phylogenetic realignments have revealed a close genetic relationship to other
      bacteria which cause human diseases, including bacterial angiomatosis, to the
      former Grahamella species which infect red cells in other mammals, and to plant
      pathogens and symbionts including Agrobacterium tumefaciens and Rhizobium
      meliloti. Features of B. bacilliformis that contribute to its pathogenesis are
      slowly coming into view, and are here reviewed.

PMID- 8870246
TI  - Evolutionary perspective on a composite Shigella flexneri 2a virulence plasmid
      borne locus comprising three distinct genetic elements.
AB  - Nucleotide sequence analysis of a Shigella flexneri 2a virulence plasmid-borne
      locus revealed that it comprised three distinct genetic elements: a stretch of
      colicin 1a/1b-linked sequence, a truncated IS911 element, and a third element
      containing two ORFs that shared a high level of similarity to a Salmonella
      specific chromosomal sequence. Examination of other known IS911-like sequences
      showed that these sequences also were frequently associated with other accessory
      elements and appeared to be prone to partial deletion events. Analysis of the
      data led to a model of the evolution of this unusual composite locus.

PMID- 8870247
TI  - Drastically decreased transcription from CII-activated promoters is responsible
      for impaired lysogenization of the Escherichia coli rpoA341 mutant by
      bacteriophage lambda.
AB  - It was demonstrated previously that a mutation, rpoA341, in the gene encoding the
      alpha subunit of Escherichia coli RNA polymerase prevents lysogenization by
      bacteriophage lambda. The rpoA341 allele is known to be responsible for impaired
      transcription of some positively regulated E. coli chromosomal operons. Here we
      demonstrate that the inhibition of lysogenization of the rpoA341 mutant is a
      result of drastically decreased transcription from positively regulated phage
      promoters. We were unable to detect any transcripts originating from the CII
      activated pE, pI and paQ promoters (important for lysogenic development) in the
      phage-infected rpoA341 mutant, in contrast to an otherwise isogenic rpoA+ strain.
      The results are discussed in the light of other reports showing that activation
      of the pE promoter by CII protein in vitro is decreased only about fivefold when
      the native alpha subunit is replaced by truncated alpha polypeptides.

PMID- 8870248
TI  - Human serum antibody response against iron-repressible outer membrane proteins of
      Helicobacter pylori.
AB  - In Helicobacter pylori, in vitro iron limitation induces the expression of
      several iron repressible outer membrane proteins (IROMPs), which are not
      expressed under normal growth conditions. To substantiate their proposed role in
      virulence of H. pylori, we determined whether these IROMPs are also expressed in
      vivo. Therefore, we tested whether sera of patients with H. pylori infection
      contained antibodies against IROMPs. All sera from 20 H. pylori positive patients
      showed a clear immune response against a 77 kDa heme-binding IROMP in an
      immunoblot assay. Antibody responses against the other IROMPs were also found,
      but with lower frequencies. Serum samples from 18 patients negative for H. pylori
      infection did not show any immunoreactivity with IROMPs. These results indicate
      that the IROMPs of H. pylori are immunogenic and are expressed in vivo.

PMID- 8870249
TI  - A collagen binding protein from Lactobacillus reuteri is part of an ABC
      transporter system?
AB  - The gene coding for a collagen binding protein from Lactobacillus reuteri NCIB
      11951 was cloned and sequenced. A genomic lambda library was constructed and
      recombinant plaques were screened using antisera raised against purified collagen
      binding proteins from the same L. reuteri strain. The positive plaques were
      subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      Western blot analysis, which revealed the expression of a 29 kDa protein, which
      reacted with the antisera and bound 125I-labelled type I collagen. The sequence
      of the corresponding gene, cnb showed that the collagen binding protein has
      sequence similarities to the solute binding component of bacterial ABC
      transporters.

PMID- 8870250
TI  - Borrelia burgdorferi possesses a collagenolytic activity.
AB  - Lyme disease is a multisystemic disorder caused by Borrelia burgdorferi, an
      invasive spirochete. B. burgdorferi has a predilection for collagenous tissue and
      one major clinical manifestation of the disease is arthritis. We have identified
      a collagenolytic activity in B. burgdorferi detergent lysates using iodinated
      gelatin as well as iodinated pepsinized human collagen types II and IV as protein
      substrates. In addition, we describe several proteolytic activities in B.
      burgdorferi with molecular masses greater than 200 kDa on sodium dodecyl sulfate
      polyacrylamide gels containing copolymerized gelatin. We propose that the
      collagenolytic activity of B. burgdorferi has a role in invasion, in the
      pathogenesis of Lyme arthritis, and perhaps also in other manifestations of Lyme
      borreliosis.

PMID- 8870251
TI  - Analysis of isoniazid-resistant transposon mutants of Mycobacterium smegmatis.
AB  - The emergence of multidrug-resistant tuberculosis has renewed interest in the
      study of drug resistance in mycobacteria with the objective of improved
      chemotherapy. The genetic basis of isoniazid resistance in a model mycobacterium
      was studied. Eleven isoniazid-resistant mutants of Mycobacterium smegmatis were
      created using transposon mutagenesis. Genetic and enzymatic characterisation of
      the mutants showed that katG, encoding T-catalase, was inactivated. The
      nucleotide sequence of M. smegmatis katG was determined and the mutation sites
      mapped demonstrating that both the amino and carboxyl halves of T-catalase are
      important for enzymatic activity.

PMID- 8870252
TI  - Cloning, sequencing and complementation analysis of the recA gene from Prevotella
      ruminicola.
AB  - Degenerate PCR primers based on conserved RecA protein regions were used to
      amplify a portion of recA [corrected] from Prevotella ruminicola strain 23, which
      was used as a probe to isolate the full-length recA gene from the P. ruminicola
      genomic library. The P. ruminicola recA gene encoded a protein of 340 amino acids
      with a molecular mass of 36.81 kDa, P. ruminicola RecA was highly similar to
      other RecA proteins and most closely resembled that of Bacteroides fragilis (75%
      identity). It alleviated the methyl methanesulfonate and mitomycin C
      sensitivities of Escherichia coli recA mutants, but did not restore the
      resistance to UV-light irradiation. Mitomycin C treatment of otherwise isogenic
      E. coli strains showed a higher level of prophage induction in a recA harboring
      lysogen.

PMID- 8870253
TI  - Regulation of the iron uptake genes in Pseudomonas fluorescens M114 by
      pseudobactin M114: the pbrA sigma factor gene does not mediate the siderophore
      regulatory response.
AB  - The iron-regulated PbrA sigma factor dictates the production of the siderophore,
      pseudobactin M114, and its cognate outer membrane receptor, PbuA, in Pseudomonas
      fluorescens M114. However, the siderophore molecule also has a role in regulating
      the expression of the siderophore biosynthetic and siderophore receptor genes in
      P. fluorescens M114. This is based on the fact that beta-galactosidase levels
      from lacZ fusions of M114 siderophore promoters (biosynthetic and receptor) were
      reduced in M114 siderophore biosynthetic mutants compared to wild-type M114.
      Expression of both promoters was increased by the addition of pseudobactin M114
      to the growth medium. This effect was widespread and applicable to all but one of
      the siderophore negative strains of M114 tested. Furthermore, it was demonstrated
      that transcription of the pbr A sigma factor gene was not reduced in the
      siderophore biosynthetic mutants. This excludes the possibility that reduced
      expression of the siderophore biosynthetic and receptor promoters in the
      siderophore biosynthetic mutants is mediated at the level of expression of the
      pbr A gene itself. In addition, it was noted that the siderophore regulated
      response was applicable to promoters with and without the DNA sequence motif,
      (G/C)CTAAATCCC, which is required for iron-regulated expression of some
      pseudomonad promoters.

PMID- 8870254
TI  - Utilization of acetonitrile and other aliphatic nitriles by a Candida famata
      strain.
AB  - A variant of a yeast strain identified as Candida famata isolated from gold mine
      effluent was able to grow on acetonitrile, acrylonitrile, butyronitrile,
      isobutyronitrile, methacrylnitrile, propionitrile, succinonitrile, valeronitrile,
      acetamide, isobutyamide, and succinamide as sole nitrogen source, after
      acclimatization. The yeast grew on acetonitrile and acetamide at concentrations
      up to 4%. The utilisation of acetonitrile and acetamide by the C. famata strain
      probably involves hydrolysis in a two-step reaction mediated by both inducible
      and intracellular nitrile hydratase and amidase.

PMID- 8870255
TI  - Molecular and genetic analysis of multiple changes in the levels of production of
      virulence factors in a subcultured variant of Streptococcus mutans.
AB  - We previously isolated a variant strain, Xc100L, which shows decreased production
      of a surface protein antigen with a molecular mass of 190 kDa (PAc), after
      repeated subculturing of Streptococcus mutans strain Xc [Koga, T. et al. (1989)
      J.Gen. Microbiol. 135, 3199-3202]. In the present study, the levels of expression
      of the gtfB, gtfC, gtfD and ftf genes coding for polysaccharide-synthesizing
      enzymes in strain Xc100L were compared with those in strain Xc. Western blot
      analysis revealed multiple differences in the levels of production of these
      enzymes between these two strains. The amounts of the gtfB and gtfC gene products
      responsible for water-insoluble glucan synthesis in strain Xc100L were lower than
      those in strain Xc, whereas the amounts of the gtfD and ftf gene products
      responsible for water soluble glucan synthesis and fructan synthesis,
      respectively, in strain Xc100L were higher than those in strain Xc. Northern blot
      analysis revealed that the amounts of the four enzymes and PAc produced by strain
      Xc100L reflected the relative amounts of mRNAs from the genes. The
      chloramphenicol acetyltransferase gene was fused with each of these five genes,
      and the transcriptional activity of each gene in strain Xc100L was quantitatively
      compared with that in strain Xc. The chloramphenicol acetyltransferase assay also
      indicated that the phenotypic differences between strain Xc and strain Xc100L
      were due to differences in the transcriptional activities of the virulence genes.
      No differences in the nucleotide sequences of the promoter regions of the gtfB,
      gtfC, gtfD, ftf and pac genes were found between strain Xc and strain Xc100L. It
      is possible that a factor(s) affecting the levels of transcription of the
      multiple virulence genes exists in S. mutans.

PMID- 8870256
TI  - Evidence for a role of NisT in transport of the lantibiotic nisin produced by
      Lactococcus lactis N8.
AB  - The biosynthesis, immunity and regulation of nisin, a lanthionine-containing
      antimicrobial peptide produced by Lactococcus lactis, is encoded by two gene
      clusters, nisA/ZBTCIPRK and nisFEG. The mutant strain LAC46 with a deletion in
      the translocator gene nisT could not secrete nisin but nisin activity was
      detected from cell lysates. The nisT mutation was complemented by a NisT
      expression plasmid resulting in restored capacity to secrete nisin. These results
      demonstrate that NisT is the transport protein dedicated to translocate nisin and
      that dehydration and lanthionine formation in nisin maturation can occur
      independently of transport.

PMID- 8870257
TI  - Phylogenetic analysis of tnpR genes in mercury resistant soil bacteria: the
      relationship between DNA sequencing and RFLP typing approaches.
AB  - The diversity of resolvase (tnpR) genes carried by a number of mercury resistant
      soil bacteria has been investigated by DNA sequencing. The resulting DNA sequence
      information was compared to previously published tnpR DNA sequences and to
      previously published restriction fragment length polymorphism (RFLP) data,
      permitting the relationships between DNA sequencing and RFLP approaches to be
      studied by the use of phylogenetic trees. DNA maximum likelihood and DNA
      parsimony were used to construct a variety of phylogenetic trees. DNA sequencing
      confirmed the validity of RFLP analysis and highlighted the importance of
      restriction endonuclease choice upon the resulting RFLP patterns and dendrogram
      topology. The tnpR genes of two previously uncharacterised mercury resistant
      bacteria, T2-7 and T2-12 were also studied. DNA sequence data placed T2-7 in a
      previously described gene class, tnpR-D and T2-12 in a new gene class, tnpR-F.
      The significance of this data with respect to the recombination and evolution
      events occurring within bacterial populations are discussed.

PMID- 8870258
TI  - Rifampicin resistance and mutation of the rpoB gene in Mycobacterium
      tuberculosis.
AB  - Using 39 clinical isolates of Mycobacterium strains with a broad range of
      susceptibility to rifampicin, we examined the relationship between the degree of
      resistance to rifampicin and mutational sites of the rpoB gene. All rifampicin
      resistant strains had missense mutations. Twenty strains (95%) had a mutation in
      the cluster I region, which has also been reported in Escherichia coli [Jin and
      Gross (1988) J. Mol. Biol. 202, 45-58], and the remaining one strain had a
      mutation at codon 381 [Ala-->Val] in the N-terminal region, which has not been
      reported in E. coli. Among 18 rifampicin-susceptible strains, two had a mutation
      in the cluster I region and the other three strains had a mutation in the cluster
      III region. The mutations at codons 513 (5%), 526 (33%) or 531 (43%) in the
      cluster I region led to high level resistance to rifampicin (50 micrograms ml-1 <
      or = MIC). The mutations at the other sites, in the cluster III region (codons
      679 or 687) and even in the cluster I region (codon 514, 521, or 533), showed low
      level (MIC = 12.5 micrograms ml-1) or no (MIC < 0.39 microgram ml-1) resistance
      to rifampicin. These results suggest that mutations in the rpoB gene are, mostly,
      but not necessarily, associated with rifampicin resistance of M. tuberculosis,
      and the sites of mutations on the rpoB gene will affect the level of resistance
      to rifampicin.

PMID- 8870259
TI  - Enhancement of frame-shift mutation by the overproduction of msDNA in Escherichia
      coli.
AB  - A minor population of wild Escherichia coli strains contain retroelements called
      retrons, which produce a peculiar satellite DNA, multicopy single-stranded DNA
      (msDNA). It has been reported that mismatched base pairs in the secondary
      structure formed in msDNA are mutagenic in E. coli[Maas et al.(1994)
      Mol.Microbiol. 14,437-441; Maas et al. (1996) Mol. Microbiol, 19, 505-509]. We
      reexamined this proposal by converting mismatched base pairs to matched base
      pairs using a single msDNA species, msDNA-Ec86, or by deleting mismatched regions
      using msDNA-Ec73. We also examined the effect of reverse transcriptases (RT)
      without msDNA production on mutagenesis. All the constructs are under the lpp/lac
      promoter-operator control so that their mutagenic effects can be tested in the
      absence and the presence of a lac inducer. It was found that when the production
      of msDNA-Ec86 or Ec73 was induced, reversion frequencies from Lac- to Lac+
      significantly increased in the case of a Lac- mutation caused by a frame-shift
      mutation, but much less by a substitution mutation. The removal of mismatched
      base pairs eliminated the high mutation frequencies, and the inducible expression
      of RT alone was not mutagenic. These results are consistent with the hypothesis
      of Maas and his associates that mismatched base pairs in msDNA sequester a
      cellular mismatch repair system, resulting in the increase of frame-shift
      mutations.

PMID- 8870260
TI  - Energetics of lactation in harp seals (Phoca groenlandica) from the Gulf of St.
      Lawrence, Canada.
AB  - This study reports the findings of an integrated, comprehensive analysis of
      lactation energetics in harp seals conducted using longitudinal measurements of
      mass, body composition and milk composition from mother-pup pairs in conjunction
      with water flux measurements in pups. The nursing period of harp seals is a
      short, intense and relatively efficient period of energy transfer from mothers to
      pups. The average daily milk intake for pups was 3.65 +/- 0.24 kg which is
      equivalent to 79.5 MJ of energy. Eighty-one per cent of the energy received in
      the milk was metabolisable and 66% of the energy was stored by the pups as body
      tissue. The field metabolic rate of pups was 3.9 +/- 0.4 time basal metabolic
      rate. The pups were growing at a rate of 2.2 kg per day during the nursing
      period. The distribution of this mass gain varied in terms of tissue composition,
      depending on the age of the pups, but over the whole nursing period approximately
      half of the tissue was stored as fat. Harp seal mothers lost an average of 3.1 kg
      per day during lactation which was composed of 37% water, 50% fat, 11% protein
      and 2% ash. Mothers spent half of their time during the lactation period actively
      diving and only one-third of their time on the surface of the ice. Milk
      compositional changes followed the normal phocid pattern with increasing fat
      content and decreasing water content as lactation progressed. The mean mass
      transfer efficiency was 73%. However, this value cannot be used without
      qualification because female harp seals in this study fed to varying degrees,
      consuming an estimated 0-4.8 kg of fish per day. Feeding does not appear to be
      required in order to achieve the energy requirements for lactation, given the
      energy stores possessed by females, and some females do fast through the entire
      period so feeding may be considered opportunistic in nature.

PMID- 8870261
TI  - Effects of saturated fatty acids on amylase release from exocrine pancreatic
      segments of sheep, rats, hamsters, field voles and mice.
AB  - Stimulatory effects of saturated fatty acids consisting of 4 (butyrate), 8
      (octanoate), 12 (laurate) and 16 (palmitate) carbon atoms, as well as
      acetylcholine on pancreatic amylase release were assessed in tissue segments
      isolated from sheep, rats, hamsters, field voles and mice. The amount of amylase
      release induced by the fatty acids (1 mumol.l-1 to 10 mml.l-1) and by
      acetylcholine (10 nmol.l-1 to 100 mumol.l-1) increased in a concentration
      dependent manner, and the maximum response in response to the fatty acids was
      obtained at the maximal dose used. The maximum increase in amylase release in
      response to butyrate or octanoate was highly and significantly (r = 0.974, P <
      0.001) dependent on the log value of the mean body mass in the following order:
      sheep > rats > hamsters > field voles > mice. On the other hand, the response to
      laurate and palmitate was variable among animal species. Addition of atropine
      (1.4 mumol.l-1) to the medium did not reduce the responses to octanoate
      stimulation, but significantly reduced acetylcholine-induced responses, implying
      that the effects of the fatty acids were not mediated through activation of
      muscarinic acetylcholine receptors. Reduction of calcium ion concentration in the
      medium significantly inhibited the responses induced by the fatty acids and
      acetylcholine, suggesting that amylase release depends on extracellular calcium
      ions.

PMID- 8870262
TI  - Cloning and expression of cathepsin L-like proteinases in the hepatopancreas of
      the shrimp Penaeus vannamei during the intermolt cycle.
AB  - Cysteine protease activities have been characterized with benzyloxycarbonyl
      lysine p-nitrophenyl ester as a synthetic substrate and E64 as a specific
      inhibitor in the hepatopancreas of the shrimp Penaeus vannamei. An optimum pH of
      5.1 has been measured. To characterize these cysteine proteases, a hepatopancreas
      cDNA library was screened by hybridization to a Norway lobster cysteine protease
      cDNA fragment. Two cDNAs encoding P. vannamei cysteine protease precursors have
      been cloned and sequenced. The encoded polypeptides have 326 and 322 amino acid
      residues, respectively, each consisting of partial signal sequences (15 and 10
      residues), a pro-region (93 and 94 residues), and a mature enzyme polypeptide
      (218 residues). Cys25, His159 and Asn175 form the catalytic triad in the putative
      active site of the mature enzymes. Compared with invertebrate cysteine proteases
      (Homarus and Fasciola), each of the two shrimp enzymes shows 70 and 52% amino
      acid sequence identity, respectively; 63% identity is shown with rat cathepsin L.
      Northern hybridization analysis showed the same size for the different cysteine
      protease transcripts in hepatopancreas tissue (approximately 1.1 kb). During
      intermolt cycles, variations in cysteine protease activity were correlated with
      the variations in the levels of specific mRNA.

PMID- 8870263
TI  - Summer torpor in African woodland dormice Graphiurus murinus
      (Myoxidae:Graphiurinae).
AB  - We determined the effect of food availability (presence/absence) and ambient
      temperature (25/10 degrees C) on daily energy expenditure and the use of activity
      and torpor in summer-acclimated captive Graphiurus murinus. Daily energy
      expenditure declined logarithmically with duration of food deprivation at a mean
      rate of 11 and 31% per day at 25 and 10 degrees C, respectively. The incidence of
      torpor in the presence of food at 25 degrees C was low (one in seven individuals)
      and increased on a single day's exposure to 10 degrees C and with duration of
      food deprivation. Use of torpor was highest during the day, varied between
      individuals, and torpor bouts of greater than 24 h duration were not noted. With
      food deprivation, individuals at 25 degrees C initially responded by reducing
      activity but remained euthermic while the same individuals at 10 degrees C
      responded by increasing their use of torpor during the light period: this
      difference in response probably reflects a difference in the relative energetic
      benefits of torpor at different temperatures.

PMID- 8870264
TI  - Oxygen consumption by ammocoetes of the lamprey Geotria australis in air.
AB  - When covered by moistened lint-free gauze, the larvae (ammocoetes) of the lamprey
      Geotria australis survived, without apparent discomfort, for 4 days in water
      saturated air at 10, 15 and 20 degrees C. In air, the mean standard rates of O2
      consumption of medium to large ammocoetes of G. australis (mean = 0.52 g) at 10,
      15 and 20 degrees C were 14.5, 35.7 and 52.1 microliters.g-1.h-1, respectively.
      At 15 degrees C, the slope of the relationship between log O2 consumption
      (microliter O2.h-1) and log body weight for ammocoetes over a wide range in body
      weight was 0.987. The Q10s for rate of O2 consumption between 10 and 15 degrees
      C, 15 and 20 degrees C and 10 and 20 degrees C were 4.9, 2.9 and 3.6,
      respectively. Our results and observations of the ammocoetes suggest that, when
      out of water, larval G. australis derives most of its O2 requirements from
      cutaneous respiration, particularly at lower temperatures. This would be
      facilitated by the small size and elongate shape (and thus a relatively high
      surface-to-volume ratio), low metabolic rate, thin dermis, extensive subdermal
      capillary network and high haemoglobin concentration of larval G. australis.

PMID- 8870265
TI  - Osmotic stress effects on the freezing tolerance of the antarctic nematode
      Panagrolaimus davidi.
AB  - The freezing and freezing survival of the Antarctic nematode Panagrolaimus davidi
      after exposure to solutions of different osmotic concentrations has been examined
      using a thermoelectric cooling stage and multi-specimen cooling block to see if
      there is any evidence that freeze-induced desiccation prevents inoculative
      freezing. The nematodes froze in all the test solutions used (up to 1138 mosmol.l
      1) and at all cooling rates and nucleation temperatures tested. Freezing survival
      was at its maximum in 0.1 mol.l-1 NaCl in artificial tap water after 1 h exposure
      to the test solution and in artificial tap water after 24 h exposure.
      Hyperosmotic and hyposmotic stress adversely affected the nematodes' ability to
      survive freezing. In nonfrozen controls survival declined with increasing
      osmolality of the test solution. Measurements of the osmolality of water
      extracted from a variety of moss samples indicate that the nematodes are exposed
      to an osmotic concentration of about 9 mosmol.l-1 in their natural habitat. This
      is close to that of artificial tap water. Our experiments, and measurements of
      freeze concentration effects in the literature, indicate that freeze-induced
      desiccation is unlikely to prevent inoculative freezing and the survival of
      nematodes over the winter.

PMID- 8870266
TI  - Analysis of the C-terminal secretion signal of the Rhizobium leguminosarum
      nodulation protein NodO; a potential system for the secretion of heterologous
      proteins during nodule invasion.
AB  - We used deletions to analyze the domains required for secretion of the Rhizobium
      leguminosarum bv. viciae nodulation protein, NodO, by the sec-independent
      pathway. Deletion of the C-terminal 24 amino-acids (residues 261 to 284) reduced
      secretion by at least 95%. A monoclonal antibody that recognizes the C-terminal
      domain of NodO was used to identify four nested deletions that retained the C
      terminal 24 residues of NodO but had lost up to 133 residues (amino acids 128 to
      259); all four proteins were secreted into the growth medium with an efficiency
      between 50 and 90% of normal. A deleted derivative of NodO that retained residues
      1 to 21 and 167 to 284 (and therefore lacked most of the N-terminal Ca(2+)
      binding domain) was secreted at around 80% of normal efficiency. Taken together,
      these observations indicate that the C-terminal 24 amino acids are sufficient for
      NodO secretion although the region adjacent to this domain appears to affect
      secretion efficiency. A derivative of the Escherichia coli alkaline phosphatase
      (phoA) gene was cloned into two derivatives of nodO such that PhoA (lacking the N
      terminal transit peptide) was in-frame at both ends, with the C terminus fused to
      either the last 24 or 50 amino acids of NodO. These fusion proteins were secreted
      at 40 and 80% of the wild-type level, respectively, and the larger of the two
      retained alkaline phosphatase activity. A hybrid protein, containing E. coli beta
      glucuronidase (GUS) fused to the N terminus of NodO, was not secreted, and it
      reduced the levels of wild-type NodO secreted by R. leguminosarum bv. viciae. The
      nature of the NodO C-terminal secretion signal is discussed with regard to its
      use as a delivery system for heterologous proteins useful for investigating the
      Rhizobium-legume interaction.

PMID- 8870267
TI  - Expression of class I O-methyltransferase in healthy and TMV-infected tobacco.
AB  - Tobacco possesses two distinct classes of O-methyltransferases (OMTs; S-adenosyl
      L-methionine:o-diphenol O-methyltransferases; EC 2.1.1.6). Here we report on the
      cloning and the expression pattern of the class I OMT that is specifically
      involved in lignin biosynthesis. Near-full-length cDNAs have been isolated from
      tobacco libraries constructed from leaf and stem poly(A)+ RNA. Sequence analysis
      demonstrated that the OMT I clones derived from two different mRNA species. The
      two types of OMT I mRNA were reverse transcribed from total RNA and the cDNAs
      were amplified by polymerase chain reaction and characterized by restriction
      analysis. The same proportion of the two transcripts was measured in stem tissue
      of healthy plants and in leaves reacting hypersensitively to tobacco mosaic
      virus, indicating a coordinate expression of the two OMT I genes. Consistently,
      genomic hybridization indicated the presence of two OMT I genes in the
      amphidiploid genome of tobacco. The pattern of expression of OMT I genes was
      studied by in situ mRNA hybridization. In stem, petiole, and root tissues, OMT I
      genes were found to be specifically expressed in vascular cells and epidermis. In
      healthy leaves OMT I mRNA was only detected in vascular strands, whereas, in
      leaves bearing tobacco mosaic virus-induced necrotic lesions, a particularly
      strong accumulation of the labeling was also localized in the upper and lower
      epidermis.

PMID- 8870268
TI  - Expression of cysteine protease genes in pea nodule development and senescence.
AB  - Coding sequences for two cysteine proteases were amplified from cDNA derived from
      pea nodule mRNA using primers based on conserved regions of plant cysteine
      proteases. One of the amplified cDNA sequences corresponded to a previously
      described cysteine protease gene, Cyp15a, expressed in pea shoots in response to
      dehydration (J.T. Jones and J.E. Mullet, Plant Mol. Biol. 28:1055-1065, 1995).
      Inside the pea root nodule, in situ hybridization revealed that this gene is
      expressed strongly in the apical region and more weakly in the uninfected cortex
      and in the central infected tissue where nitrogen fixation takes place. The
      complete sequence of the cDNA corresponding to the other gene, PsCyp1, was
      obtained. Expression of this gene, which was studied both on RNA blots and in
      situ, showed good correlation with the onset of nodule senescence. In situ
      hybridization studies revealed that PsCyp1 was expressed in senescent infected
      tissue at the base of the nodule. This signal was just detectable in normal
      symbiotically wild-type nodules but was much stronger in the early senescing
      nodules formed by a symbiotically defective mutant of Rhizobium leguminosarum.

PMID- 8870269
TI  - HrpG, a key hrp regulatory protein of Xanthomonas campestris pv. vesicatoria is
      homologous to two-component response regulators.
AB  - Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot
      disease of pepper and tomato plants. Expression of its basic pathogenicity genes,
      the hrp genes, is induced in planta and in XVM2 medium and is dependent on the
      hrp regulatory gene hrpXv for five out of six loci in the 23-kb hrp cluster. Here
      we describe the isolation of a novel hrp gene, hrpG, that was identified after
      chemical mutagenesis and that is located next to the hrpXv gene. In a hrpG mutant
      induction of expression of the seven loci hrpA to hrpF, and hrpXv is abolished,
      suggesting that hrpG functions at the top of the hrp gene regulatory cascade.
      hrpG is the only gene in the locus and encodes a putative protein of 263 amino
      acids with a molecular mass of 28.9 kDa. The HrpG amino acid sequence shows
      similarity to response regulator proteins of the OmpR subclass of two-component
      systems, being mostly related to the ChvI proteins of Agrobacterium tumefaciens
      and Rhizobium spp., and TctD of Salmonella typhimurium. Expression of hrpG is low
      in complex medium, is increased in XVM2 by a factor of four, and is independent
      of other hrp loci. A model on hrp gene regulation in Xanthomonas campestris pv.
      vesicatoria is discussed.

PMID- 8870270
TI  - Defense reaction in Medicago sativa: a gene encoding a class 10 PR protein is
      expressed in vascular bundles.
AB  - Infiltration of Medicago sativa leaves with a suspension of Pseudomonas syringae
      pv. pisi elicits the accumulation of several mRNA classes. A clone, designated as
      MsPR10-1, encoding a polypeptide exhibiting strong similarity to the class 10 PR
      protein was isolated and characterized from a cDNA library prepared from leaf
      mRNA. The corresponding gene was shown to be developmentally regulated: Except in
      roots, its expression was not detectable in other analyzed organs of healthy
      plants (hypocotyls, cotyledons, stems, leaves, and flower buds). MsPR10-1
      transcript accumulation was especially high in leaf blades during an incompatible
      interaction: It was already detectable 3 h after infection, reached its maximum
      level 24 h postinfection, and remained at a high level over a period of at least
      72 h. In addition, the expression of this gene was induced by salicylic acid
      treatment of the leaves. Southern hybridizations showed that this gene belongs to
      a multigene family. Using a 5' extension technique for cDNA, we demonstrated that
      during the incompatible interaction with P. syringae pv. pisi several genes or
      allelic variants of this class were expressed. Measurements of transcript
      accumulation in both the infiltrated and noninfiltrated zones by Northern and in
      situ hybridization allowed to demonstrate the "systemic" expression pattern of
      the MsPR10-1. In situ hybridizations indicated that MsPR10-1 was expressed in the
      vascular bundles adjacent to and distant from the infection site.

PMID- 8870271
TI  - Characterization and mutational analysis of nodHPQ genes of Rhizobium sp. strain
      N33.
AB  - We have shown, by sequencing the nodulation gene region of Rhizobium sp. strain
      N33 previously isolated from the Canadian high arctic, that the nodHPQ genes are
      located in a 4.8-kb region downstream of nodBCIJ. The open reading frames of
      nodHPQ are 747, 906, and 1941 nucleotides long, respectively. The strain N33
      genome contains one copy of nodH and two copies of nodPQ that are homologous to
      those genes in Rhizobium meliloti. Tn5 insertions in the nodHPQ genes of strain
      N33 did not affect the formation of nodules on the two homologous hosts,
      Astragalus cicer and Onobrychis viciifolia. Since strain N33 contains the
      nodBCIJHPQ genes and the recently sequenced nodAFEG genes, we looked for similar
      host range with R. meliloti. Strain N33 and R. meliloti strains A2 and RCR2011
      were shown to induce the formation of root nodules on plants of O. viciifolia.
      However, strain N33, compared with R. meliloti strains, was able to elicit a few,
      white, empty, root nodules on Medicago sativa. R. meliloti strains, compared with
      strain N33, were shown to induce only few nodules containing bacteria on A.
      cicer. Induction of nod genes transcription in strain N33 was shown to be induced
      by a variety of flavonoid compounds that are different from those inducing nod
      genes from R. meliloti.

PMID- 8870272
TI  - Identification and map location of TTR1, a single locus in Arabidopsis thaliana
      that confers tolerance to tobacco ringspot nepovirus.
AB  - The interaction between Arabidopsis and the nepovirus tobacco ringspot virus
      (TRSV) was characterized. Of 97 Arabidopsis lines tested, all were susceptible
      when inoculated with TRSV grape strain. Even though there was systemic spread of
      the virs, there was a large degree of variation in symptoms as the most sensitive
      lines died 10 days after inoculation, while the most tolerant lines either were
      symptomless or developed only mild symptoms. Four lines were selected for further
      study based on their differential reactions to TRSV. Infected plants of line Col
      0 and Col-0 gl1 flowered and produced seeds like noninfected plants, while those
      of lines Estland and H55 died before producing seeds. Symptoms appeared on
      sensitive plants approximately 5 to 6 days after inoculation. Serological studies
      indicated that in mechanically inoculated seedlings, the virus, as measured by
      coat protein accumulation, developed at essentially the same rates and to the
      same levels in each of the four lines, demonstrating that differences in symptom
      development were not due to a suppression of virus accumulation. Two additional
      TRSV strains gave similar results when inoculated on the four lines. Genetic
      studies with these four Arabidopsis lines revealed segregation of a single
      incompletely dominant locus controlling tolerance to TRSV grape strain. We have
      designated this locus TTR1. By using SSLP and CAPS markers, TTR1 was mapped to
      chromosome V near the nga129 marker. Seed transmission frequency of TRSV for Col
      0 and Col-0 gl1 was over 95% and their progeny from crosses all had seed
      transmission frequencies of over 83%, which made it possible to evaluate the
      segregation of TTR1 in F2 progeny from infected F1 plants without inoculating F2
      plants. Seed transmission of TRSV will be further exploited to streamline
      selection of individuals for fine mapping the TTR1 gene. The identification of
      tolerant and sensitive interactions between TRSV and A. thaliana lines provides a
      model system for genetic and molecular analysis of plant tolerance to virus
      infection.

PMID- 8870273
TI  - Mode of action of the Arabidopsis thaliana phytoalexin camalexin and its role in
      Arabidopsis-pathogen interactions.
AB  - The virulent Arabidopsis thaliana pathogen Pseudomonas syringae pv. maculicola
      strain ES4326 (Psm ES4326) and other gram-negative bacteria are sensitive to
      camalexin (3-thiazol-2'-yl-indole), the Arabidopsis phytoalexin. Furthermore, Psm
      ES4326 is unable to degrade camalexin or to become tolerant to it. Apparently,
      Psm ES4326 is a successful pathogen even though it elicits synthesis of a host
      phytoalexin to which it is sensitive. Assays of membrane integrity revealed that,
      like other phytoalexins, camalexin disrupts bacterial membranes, suggesting that
      camalexin toxicity is a consequence of membrane disruption. A screen for
      camalexin-resistant mutants of Psm ES4326 yielded only partially resistant
      mutants, which displayed partial resistance in both killing and membrane
      integrity assays. These mutants were also resistant to low concentrations of
      tetracycline and nalidixic acid, suggesting that they were affected in components
      of the outer membrane. The mutants were not distinguishable from Psm ES4326 in
      virulence assays. Camalexin was toxic to Arabidopsis cells growing in tissue
      culture. However, comparison of the extent of cell death associated with disease
      symptoms in infected leaves of wild-type Arabidopsis and a camalexin-deficient
      mutant suggested that camalexin does not contribute significantly to cell death
      in infected tissue.

PMID- 8870274
TI  - The nucleotide sequence of the coat protein gene and 3' untranslated region of
      azuki bean mosaic potyvirus, a member of the bean common mosaic virus subgroup.
AB  - The relationship of azuki bean mosaic potyvirus (AzMV) to members of the bean
      common mosaic virus (BCMV) subgroup has been unclear. Degenerate oligonucleotide
      primers and the polymerase chain reaction were used to amplify and clone the coat
      protein (CP) gene and 3' untranslated region (UTR) of AzMV. The deduced amino
      acid sequence of the CP is 94% identical to that of dendrobium mosaic virus,
      establishing the two as strains of the same virus. While the CP amino acid
      identities between AzMV and potyviruses of the BCMV species are at or below 90%,
      the 91 to 94% identity between their UTRs suggests that AzMV could be considered
      a strain of BCMV. Interestingly, the grouping of potyviruses within the greater
      BCMV subgroup on a coat protein amino acid tree correlates with a grouping based
      on the response elicited on bean containing the I gene for resistance to BCMV.

PMID- 8870276
TI  - Gingival enlargement as a diagnostic indicator in leukaemia. Case report.
AB  - The acute leukaemias are a group of neoplastic diseases that are characterized by
      proliferation of immature white cells in the bone marrow and/or blood and are
      often associated with severe leukopenia, anaemia and thrombocytopenia. Oral
      manifestations are more common in patients with acute leukaemia. Oral bleeding,
      gingival enlargement, ulceration and infection in patients with leukaemia have
      been described. Leukaemic infiltrates in the gingivae are commonly seen in acute
      monocytic leukaemia. A case of acute monocytic leukaemia in a 34-year-old female
      who reported with gingival enlargement is presented here. The role of oral
      lesions as a diagnostic indicator is discussed.

PMID- 8870275
TI  - The use of a simple functional appliance as an adjunct to fixed appliance
      orthodontic treatment. Case reports.
AB  - Three clinical case studies are presented to demonstrate the use of a simple
      functional appliance in orthodontic situations not covered by traditionally
      accepted dental and skeletal indications. In each case, the appliance was used to
      reduce the severity of the malocclusion, before a routine fixed-appliance
      detailing phase.

PMID- 8870277
TI  - Anatomical considerations in the diagnosis and management of acute maxillofacial
      bacterial infections.
AB  - General dentists are frequently called upon to manage maxillofacial infections.
      Such infections are usually well localized in their initial stages but can spread
      to become severe and potentially life-threatening. This paper discusses the
      anatomical basis of the spread of these infections and techniques relevant to the
      rational management of these serious conditions.

PMID- 8870278
TI  - Pseudo root resorption. Case report.

PMID- 8870279
TI  - Dentistry's role in obstructive sleep apnoea. Review and case report.
AB  - Obstructive sleep apnoea (OSA) has been associated with many life-threatening
      conditions but has only recently appeared in the dental literature. Dental
      appliances and orthognathic surgery are two strategies which are currently used
      in the treatment of sleep apnoea. This article provides a background on OSA and
      these treatment approaches, and discusses the potential risks and benefits of
      each. A case is reported to illustrate the use of a dental appliance in the
      treatment of OSA.

PMID- 8870280
TI  - Prevalence of orofacial injuries and use of mouthguards in high school Rugby
      Union.
AB  - In Australia there is a tradition of early involvement of children in contact
      sports. Mouthguards are known to reduce the risk of dental and associated
      injuries--however, Australian studies of the use of mouthguards in contact sports
      and the prevalence of dental and associated injuries have only focused on adult
      participants. Previous studies of high school Rugby Union players in New Zealand
      have shown that between 13 and 15 per cent had previously sustained dental injury
      while between 30 and 37 per cent wore mouthguards regularly. One hundred and
      thirty Rugby Union football players attending a large high school in Brisbane
      participated in this survey. All believed in the safety value of mouthguards in
      football. All of the players in the four open teams and the majority of players
      in the four under-age teams wore mouthguards, and the incidence of dental injury
      was very low, approximately 4 per cent. These and other results will be presented
      and compared with previous similar studies.

PMID- 8870281
TI  - Factors affecting the amount of long-term restorative dental treatment provided
      to 100 patients by 20 dentists in 3 Adelaide private practices.
AB  - Apart from the effects of the frequency of patient attendance for dental
      examination, and of a change of dentist, little is known of those factors which
      may influence the amount of treatment provided in dental practice. The present
      study investigated during 1992 the effects of seven factors on the amount of
      treatment provided for 100 adult patients treated by 20 male dentists over many
      years in three selected Adelaide private practices. The amounts of particular
      types of restorative treatments provided were significantly related to patient
      age, gender and frequency of attendance, and to practice location, change of
      dentist and number of changes of dentist, and to the experience or time since
      graduation of the dentist. These factors were of special significance for the
      number of crowns provided, most of which were placed in older patients by more
      experienced dentists. But, there was no evidence of increased numbers of direct
      placement restorations being received by patients who attended more frequently or
      who changed their dentists.

PMID- 8870282
TI  - The life of Henry Jeanneret (1802-1886). Pioneer Australian dentist. With an
      account of his colonial service and scientific contributions in Australia.
AB  - Henry Jeanneret was a pioneer Australian dentist, perhaps the first in this
      country to promote the discipline of dentistry as distinct from medicine and
      general surgery. This profile describes his early life and training, his
      emigration to Australia, his clinical practice in Sydney and in Van Diemen's
      Land, and his contributions to natural history, particularly in the field of
      botany.

PMID- 8870283
TI  - Complaints--why do they happen?

PMID- 8870284
TI  - Oral health and personnel needs in the Pacific.

PMID- 8870285
TI  - The stability of facial osteotomies.

PMID- 8870286
TI  - Anxiety sensitivity, suffocation fear, trait anxiety, and breath-holding duration
      as predictors of response to carbon dioxide challenge.
AB  - We investigated predictors of response to carbon dioxide challenge (i.e.
      breathing deeply and rapidly into a paper bag for 5 min) in college students.
      Zero-order correlations indicated that scores on both the Anxiety Sensitivity
      Index (ASI: Reiss, Peterson, Gursky & McNally, 1986) and the Suffocation Fear
      Scale (SFS: Rachman & Taylor, 1994), predicted anxious response to challenge,
      whereas a behavioral measure of carbon dioxide sensitivity (i.e. maximum breath
      holding duration) and scores on the State-Trait Anxiety Inventory--Trait form
      (STAI-T: Spielberger, Gorsuch, Lushene, Vagg & Jacobs, 1983) did not. Multiple
      regression revealed that all four variables remained in the model, entering in
      the following order: ASI, breath-holding duration, SFS, and STAI-T. These data
      suggest that psychological variables reflecting fears of bodily sensations are
      better predictors of response to challenge than either behavioral sensitivity to
      carbon dioxide or general trait anxiety.

PMID- 8870287
TI  - Fearful responding to repeated CO2 inhalation: a preliminary investigation.
AB  - In an effort to explore factors which maintain fear of physical sensations,
      repeated administration of 35% CO2 was used with college students scoring high
      and low on the Anxiety Sensitivity Index. Half of each group was administered 12
      CO2 trials, while the other half received 9 CO2 trials, followed by a
      dishabituation trial (Trial 10) and 2 more CO2 administrations (Trials 11 and
      12). Measures included subjective anxiety, heart rate, skin conductance, and
      number of panic symptoms reported. Results indicated a nonsignificant trend for
      the High ASI group to show increased pre-inhalation anxiety across trials, while
      the Low ASI group showed a rapid reduction in pre-inhalation anxiety. Post
      inhalation skin conductance mirrored this pattern, although rapid reduction in
      post-inhalation heart rate was observed. Overall, the High ASI participants
      showed a notable lack of fear reduction across trials. Results are discussed in
      light of sensitization as a factor contributing to anticipatory anxiety, with
      implications for understanding the etiology and maintenance of Panic Disorder.

PMID- 8870288
TI  - The sensitivity theory of motivation: implications for psychopathology.
AB  - Sensitivity theory holds that people differ in both the types of reinforcement
      they desire and in the amounts of reinforcement they need to satiate. People who
      crave too much love, too much attention, too much acceptance, too much
      companionship, or too much of some other fundamental reinforcer are at risk for
      aberrant behavior because normative behavior does not produce the desired amounts
      of reinforcement. People who are intolerant of even everyday amounts of anxiety
      or frustration also are at risk for aberrant behavior. Individual differences in
      desired amounts of particular reinforcers may predict person-environment
      interactions, risk factors for psychopathology, and the occurrence of generalized
      and durable therapy effects versus the occurrence of relapses. Parallel
      predictions are made for individual differences in tolerance of aversive stimuli.
      Implications are discussed for applied behavior analysis, the development of
      psychopathology, and treatment strategies.

PMID- 8870289
TI  - Directed forgetting in obsessive-compulsive disorder.
AB  - We tested whether patients with obsessive-compulsive disorder (OCD) are
      characterized by dysfunction in the ability to forget disturbing material.
      Employing a directed forgetting procedure, we presented OCD patients and healthy
      control subjects with a series of negative, positive, and neutral words, and
      instructed them either to remember or to forget each item after it was presented.
      Subjects received free recall and recognition tests for all words, regardless of
      instructions. Orthogonal planned contrasts indicated that OCD patients exhibited
      deficits in the ability to forget negative material relative to positive and
      neutral material, whereas control subjects did not. Additional analyses suggested
      that OCD patients elaboratively encoded negative words, regardless of
      instructions, thereby enhancing their memorability.

PMID- 8870290
TI  - Early avoidance of traumatic stimuli predicts chronicity of intrusive thoughts
      following burn injury.
AB  - The role of avoidance behavior in perpetuating the experience of intrusive
      thoughts among burn survivors was investigated. The Impact of Events Scale (IES),
      which has subscales that measure the frequency of intrusive thoughts and
      avoidance behavior, was administered to burn survivors (n = 23) upon discharge
      and four months later. Both avoidance behavior and intrusive thoughts at
      discharge were significantly related to experiencing intrusive thoughts at four
      months (r = 0.59, P < 0.003, r = 0.45, P < 0.03, respectively). In a hierarchical
      regression analysis controlling for intrusive thoughts at discharge, avoidance
      behavior continued to significantly predict intrusive thoughts at four months [B
      = 0.43, t(20) = 2.9, P < 0.009]. Limitations of the study and implications for
      treatment are discussed.

PMID- 8870291
TI  - The use of pharmacologic pain sensitization in the treatment of repetitive hair
      pulling.
AB  - A significant problem for many individuals who engage in repetitive hair-pulling
      is the fact that they experience no discomfort associated with their behavior,
      and can thus carry on with hair-pulling outside of conscious awareness. The
      present case study was an attempt to address this problem through the use of a
      commercially available topical cream which enhances pain sensitivity. A 38-yr-old
      female applied the cream daily to two affected areas on her scalp. The increased
      pain sensitization, in conjunction with the habit reversal technique, resulted in
      markedly decreased hair-pulling.

PMID- 8870292
TI  - Investigation into the relationship between personality traits and OCD: a
      replication employing a clinical population.
AB  - The relationship between obsessional personality traits and Obsessive Compulsive
      Disorder (OCD) has long been the subject of debate. Although clinicians have
      asserted for nearly a hundred years that such a relationship exists, empirical
      investigations have failed to provide consistent support; however, none of these
      empirical investigations have undertaken analyses that control for the effect of
      mood variables. Employing a non-clinical sample, Rosen and Tallis (1995)
      [Behaviour, Research and Therapy, 4, 445-450] found that when mood variables are
      taken into account, a unique relationship between obsessional traits and
      obsessional symptoms emerges. A replication was undertaken on a large group of
      individuals with OCD. After the effects of depression and anxiety were removed
      from a correlational analysis, obsessional symptoms were found to be
      significantly associated with obsessional and passive aggressive traits.
      Obsessive Compulsive Disorder was not associated with any other grouping of
      traits as specified in the DSM-III-R (Axis II) classification system.

PMID- 8870293
TI  - The assessment of personality disorders: implications for cognitive and behavior
      therapy.
AB  - This article reviews the comorbidity of personality disorders (PDs) and Axis I
      disorders and discusses implications for assessment and treatment. Pros and cons
      of various assessment methods are discussed. The co-occurrence of PDs with Axis I
      disorders is considerable; roughly half of patients with anxiety disorders,
      depressive disorders or eating disorders received a PD diagnosis. Comorbidity
      models are discussed and implications for assessment and treatment are provided.
      Regarding the impact of PDs on cognitive-behavioral treatment outcome for Axis I
      disorders, conflicting results are found due to differences in assessment
      methods, treatment strategies, and patient samples. It is argued that additional
      Axis I pathology should be taken into account when studying the impact of PDs on
      treatment outcome for the target Axis I disorders. Finally, it is argued that the
      interpersonal behavior of the PD patient and the therapeutic relationship deserve
      more attention in the assessment and treatment of patients with PDs.

PMID- 8870294
TI  - Psychometric properties of the PTSD Checklist (PCL).
AB  - The psychometric properties of the PTSD Checklist (PCL), a new, brief, self
      report instrument, were determined on a population of 40 motor vehicle accident
      victims and sexual assault victims using diagnoses and scores from the CAPS
      (Clinician Administered PTSD Scale) as the criteria. For the PCL as a whole, the
      correlation with the CAPS was 0.929 and diagnostic efficiency was 0.900 versus
      CAPS. Examination of the individual items showed wide ranging values of
      individual item correlations ranging from 0.386 to 0.788, and with diagnostic
      efficiencies of 0.700 or better for symptoms. We support the value of the PCL as
      a brief screening instrument for PTSD.

PMID- 8870295
TI  - The Yale-Brown Obsessive Compulsive Scale: interview versus self-report.
AB  - Several studies have demonstrated the reliability and validity of the Yale-Brown
      Obsessive Compulsive Scale (YBOCS) conducted by trained interviewers. The present
      study examined several aspects of a self-report YBOCS version relative to the
      usual interview format in two non-clinical samples (ns = 46 and 70) and in a
      clinical OCD sample (n = 36) and a clinical non-OCD group (n = 10). The self
      rated instrument showed excellent internal consistency and test-retest
      reliability, performing somewhat better than the interview. There was good
      agreement between symptom checklist categories across the two versions, though
      clinical subjects reported more symptoms on the self-report form than on the
      interview. Some order effects were evident for non-clinical subjects only: those
      who received the self-report first scored lower on both self-report and interview
      than those who received the interview first. No order effects were observed in
      the clinical sample. The self-report version showed strong convergent validity
      with the interview, and discriminated well between OCD and non-OCD patients.
      Although more study is needed, particularly on clinical samples, these findings
      suggest that the self-report YBOCS may be a time-saving and less costly
      substitute for the interview format in assessing OCD symptoms.

PMID- 8870296
TI  - Action Statement for Health Promotion in Canada.

PMID- 8870297
TI  - Surveillance support for population health decision making.

PMID- 8870298
TI  - The mercury emergency and Hamilton school children: a follow-up analysis.
AB  - In September 1993, children broke into a laboratory in an abandoned scrap metal
      recycling plant in Hamilton and removed mercury and other materials from the
      site. They began distribution of the mercury to their peers but this activity was
      halted once an emergency response was established. This paper focuses on the
      identification and assessment of children exposed to mercury and the use of Epi
      Info 6 in the analysis. Approximately 6,000 children were screened and 269
      children identified as being exposed or at risk of exposure. We found that
      distribution of mercury within the school system was swift. Children exhibited a
      number of risky behaviours with mercury. There were no significant gender
      differences in these behaviours. The majority of children involved were 10 to 13
      years of age. No child exhibited health effects from exposure.

PMID- 8870299
TI  - Persistence of Vitamin D-deficiency rickets in Toronto in the 1990s.
AB  - To assess the current picture of vitamin D deficiency, we reviewed all 17 cases
      of vitamin D-deficiency rikets seen in the referral clinic of a children's
      hospital in Toronto between 1988 and 1993. The diagnosis was made at 7 to 33
      months of age. All the children were symptomatic all had biochemical and
      radiographic abnormalities, two suffered hypocalcemic seizures, and all had
      bowing of the extremities. Twelve of the children were born to parents who were
      recent immigrants to Canada. All were of Asian or African origin with dark skin.
      All the children had been exclusively breastfed with no vitamin D
      supplementation, and had had little or no sunlight exposure. All the patients
      responded to vitamin D therapy. We conclude that vitamin D-deficiency rickets
      remains an environmental/nutritional deficiency disease in this city and that
      efforts at prevention should target children with pigmented skin from families
      who are recent immigrants.

PMID- 8870300
TI  - Breastfeeding and weaning practices in Vancouver.
AB  - This study describes infant feeding practices in Vancouver during the first nine
      months after birth, as compared with the Canadian Pediatric Society (CPS)
      guidelines and results of studies from other parts of Canada. Information on
      feeding practices and family background was obtained from parents of 434 nine
      month-old infants by questionnaire and diet history. The overall rate of
      breastfeeding initiation was 82.9%, but this differed significantly between
      Caucasian (91.6%) and non-Caucasian (56.8%) mothers. Introduction of solid foods
      occurred at ages consistent with CPS recommendations, but only 18.2% of mothers
      still breastfed at nine months' postpartum. Breastfeeding practices were
      significantly associated with the mothers' marital status, education and family
      income. Women who were single, had no post-secondary education, or had a family
      income of less than $30,000 were least likely to breastfeed, or to do so for
      longer durations. The development of educational and support systems to encourage
      longer breastfeeding among different ethnic and socioeconomic groups should be a
      priority for infant nutrition initiatives.

PMID- 8870301
TI  - Playground equipment hazards and associated injuries in Kingston and area.

PMID- 8870302
TI  - A simplified guide to practising community-based/community development
      initiatives.
AB  - The Simplified Guide to Practising Community-Based/Community Development
      Initiatives is tool for professionals who are beginning to embrace the principles
      of community development and empowerment into their philosophy of practice. The
      tool can be used to prepare for the initiative, to assist with the process, or
      afterwards to evaluate and formulate recommendations. The role of the
      professional is highlighted. One retrospective descriptive case analysis is
      presented to demonstrate the tool as an evaluation technique and to demonstrate
      the role of the practitioner in community development.

PMID- 8870303
TI  - Access to and use of physician resources by the rural and urban populations in
      Manitoba.
AB  - This paper examines access to and use of the physician resources for ambulatory
      care by residents of Winnipeg and rural areas in Manitoba. Analyses were
      conducted on physician claims submitted to Manitoba Health in the fiscal years
      1986-87 and 1991-92. The percentage of people who made contact with physicians,
      the number of visits per 100 residents, and the number of visits per user were
      used to asses changes between 1986 and 1991. There were important variations
      between residents of Winnipeg and the rural regions in access to and use of
      physicians' services across the years, and by physician specially. These
      variations accompanied a decrease in physician supply in the province.

PMID- 8870304
TI  - Hospital utilization in Ontario and the United States: the impact of
      socioeconomic status and health status.
AB  - We compared hospital use in Ontario and the United States for persons with
      different socioeconomic and health status. METHODS: Cross-sectional study using
      the 1990 Ontario Health Survey and the 1990 National Health Interview Survey.
      RESULTS: Admission rates averaged 31% higher in Ontario than in the United
      States, but international differences varied markedly across income and health
      status. At each level of health status, poor Canadians received one quarter to
      one third more admissions than their counterparts in the United States. However,
      higher income Canadians reporting excellent to good health had 50% more
      admissions than Americans, whereas those reporting fair or poor health had 10%
      fewer admissions. CONCLUSIONS: The observation that higher income sick persons
      receive less hospital care in Ontario than in the U.S. provides support at the
      population level for what has been observed for specific technologies. This
      represents, in part, a redistribution of inpatient care to those most vulnerable
      to illness, such as the poor, who receive substantially more hospital care in
      Ontario.

PMID- 8870305
TI  - Disadvantaged women and smoking.
AB  - High rates of smoking are found among disadvantaged women, and there is a demand
      for cessation interventions specifically targeted to meet their needs. This
      project used a number of information sources to examine the factors associated
      with these women's smoking behaviours and the potential barriers and supports to
      cessation. Few of the women-centred cessation programs whose representatives were
      contacted were appropriate for, or available to, disadvantaged women in Canada.
      Interviews with 386 disadvantaged women revealed that their smoking was
      intimately linked with their life situation of poverty, isolation and caregiving;
      smoking was a mechanism for coping with the stress of their lives. Agencies
      outside traditional tobacco control organizations, such as women's centres, were
      well positioned to initiate or expand services that support smoking cessation for
      these women and were trusted by the women who used their services. The findings
      have implications for programs, research and policy.

PMID- 8870306
TI  - The oral health of disadvantaged adolescents in North York, Ontario.
AB  - Disadvantaged youth such as the homeless, the unemployed or recent immigrants are
      thought to be at high risk for dental problems, but data to support this
      hypothesis are rare. Using interviews and clinical examinations, this study
      measured the oral health status and treatment needs of a convenience sample of
      478 disadvantaged adolescents aged 14 and older in North York, Ontario. Although
      the results cannot be generalized to the overall population, the data suggested
      that disadvantaged youth have high rates of oral disease. The adolescents
      reported a variety of symptoms, including oral pain and low rates of dental
      visiting. Clinically, high rates of periodontal disease, dental decay and urgent
      treatment needs were detected. If public health resources are to be directed to
      those most in need, efforts should be made to identify high-risk groups that may
      be overlooked in general surveys. Prevention, detection and treatment programs
      should be considered for high-risk adolescents.

PMID- 8870307
TI  - The Feather of Hope Aboriginal AIDS Prevention Society: a community approach to
      HIV/AIDS prevention.
AB  - Infection with the human immunodeficiency virus (HIV) is a complex and
      challenging issue for Aboriginal people in Canada. There is a need for HIV/AIDS
      prevention programs that address the specific needs of Canadian Aboriginal
      communities in a culturally accepted manner. The Feather of Hope Aboriginal AIDS
      Prevention Society provides culturally sensitive HIV prevention programs to
      Aboriginal communities in Alberta. The community development approach used by the
      Society emphasizes empowerment at the individual and group level. This approach
      is congruent with the shift to self-determination by Aboriginal people throughout
      Canada.

PMID- 8870308
TI  - The visiting lectureship on aboriginal health: an educational initiative at the
      University of Toronto.
AB  - Many recent reports on Aboriginal issues have identified three major deficits in
      Canadian universities: a lack of Aboriginal curriculum content, a lack of faculty
      role models, and low student enrollment. Many health professional schools have
      responded by recruiting more Aboriginal students and by introducing Native
      content into their curricula. This paper describes the six-year experience of the
      annual program of the Visiting Lectureship on Native Health at the University of
      Toronto as one of the ways to increase the Aboriginal curricular content. The
      three-week program covers the selected Aboriginal health issue by sequentially
      exploring its historical background, the extent of the current problem and its
      future solutions. Over six years, 37 Native speakers delivered 83 lectures, 19
      public fora and 98 seminars and workshops to 3 universities and 12 professional
      and community agencies. Over 7,900 individuals have participated in the program
      and the response has been very positive.

PMID- 8870309
TI  - Active living: just a passing fad?
AB  - The shift from a prescriptive exercise model to Canada's Active Living has
      created considerable tension in the public health and fitness fields. This study
      examined areas of consensus and debate about Active Living. Semistructured
      interviews of 42 stakeholders were conducted to capture competing perspectives.
      Several assumptions concerning the meaning of Active Living were challenged, such
      as Active Living being an inclusive and holistic concept. Limitations associated
      with the breadth of Active Living were noted (e.g., operationalization and
      measurement). Finally, areas of tension were identified: government turf battles,
      top-down pressure, fear of replacement/role-loss, perceived lack of expertise,
      and discomfort associated with the perception of Active Living as a political
      construct. If Active Living is to be more than just a passing fad, then several
      challenges must be addressed: 1) clarification and communication of Active
      Living, 2) establishment of a research base, and 3) enhanced government and
      organizational support.

PMID- 8870310
TI  - Odontogenic tumours: analysis of 148 cases in Zimbabwe.
AB  - OBJECTIVE: To review the histopathological and clinical data on odontogenic
      tumours. DESIGN: A retrospective study of 148 odontogenic tumours seen over a 10
      year period. SETTING: Department of Oral and Maxillofacial Surgery at Harare
      Central Hospital, Harare, Zimbabwe. SUBJECTS: Histopathologic records of patients
      with odontogenic tumour. MAIN OUTCOME MEASURES: Age and sex distribution of the
      various tumours. Frequency distribution of tumours. RESULTS: From a total of 1723
      biopsies over a 10 year period, 8.6pc were tumours of odontogenic origin.
      Ameloblastoma comprised 79.1pc of the odontogenic tumours. CONCLUSION:
      Odontogenic tumours are uncommon lesions,8,6pc. Ameloblastoma is the commonest
      odontogenic tumour, 79.1pc. The only malignant odontogenic tumour noted was
      ameloblastic fibro-sarcoma, 0.7pc.

PMID- 8870311
TI  - Knowledge on collection and analysis of health information of state certified
      nurses from rural health centres, Masvingo Province.
AB  - OBJECTIVE: To assess the knowledge on collection and analysis of health
      information of State Certified Nurses (SCNs) from Rural Health Centres (RHCs),
      Masvingo Province. DESIGN: Three methods were employed during the assessment: a
      questionnaire, observation, and practical exercises (calculations). SETTINGS: 19
      RHCs in Chiredzi and Bikita Districts, Masvingo Province. SUBJECTS: 19 SCNs in
      charge of Rural Health Centres. MAIN OUTCOME MEASURES: Ability to analyze and
      utilize health information, availability of graphs, master cards summaries
      (health diaries) and minutes. Presence or absence of catchment maps, charts on
      population breakdown and immunization coverage charts. Ability to calculate some
      rates and percentages. RESULTS: Of 19 SCNs in charge who said they do school
      health programmes, only six had any evidence that they do so; of nine SCNs in
      charge who reported that they have graphs on weekly reported diseases, only four
      had graphs displayed. Of 18 SCNs in charge who said they had immunization
      coverage targets only 11 had charts displayed; of 18 SCNs in charge who reported
      that they discuss health problems in their areas, only one had minutes
      documenting the discussion. Only six of 19 SCNs at rural centres could calculate
      coverage rates and only one of 19 SCNs at health centres could calculate dropout
      rates. CONCLUSION: Comparing the questionnaire responses with the findings from
      observations, it can be seen that more is reported than is actually done. From
      the practical exercises it was evident that the ability to do basic calculations
      was often lacking.

PMID- 8870312
TI  - Hypoxaemia and bronchopneumonia in infants less than six months of age.
AB  - OBJECTIVE: To determine the association of both oxygen saturation (SaO2) in high
      levels of inspired oxygen (FiO2) and the rate of desaturation in air among
      survivors and non survivors (death within 7 days of admission) in infants with
      bronchopneumonia. DESIGN: Hospital based prognostic study. SETTING: Tertiary
      level Paediatric ward, Harare Hospital. SUBJECTS: Total of 40 infants aged less
      than six months with pneumonia were studied. INTERVENTIONS: Oxygen saturation was
      measured with a pulse oximeter and F1O2 with an analyser. F1O2 was increased
      until the SaO2 reached maximal values, SaO2 was recorded for five minutes: three
      in O2 (oxygen) and two in air and the rate of desaturation calculated. MAIN
      OUTCOME MEASURES: Mortality within seven days of admission. RESULTS: Eleven died
      within seven days of admission. Mortality was not associated with age, weight for
      age, severity of pneumonia, or SaO2 in high oxygen (99pc versus 95pc). It was
      related to the rate of oxygen desaturation in air; 8pc/minute versus 24pc/minute
      in survivors and non survivors, respectively (p < 0.001). CONCLUSION: This study
      suggests that current nursing procedures and feeding practices may need to be
      modified in these very ill infants.

PMID- 8870313
TI  - Undifferentiated systemic connective tissue disease-"overlap' in Zimbabwe.
AB  - OBJECTIVE: To define the clinical characteristics of the overlapping,
      undifferentiated systemic connective tissue disease in one of the tropical
      African countries. DESIGN: A descriptive retrospective study of records of
      patients registered on a special rheumatology clinic between 1989 and 1994.
      SETTING: Harare Central Hospital Rheumatology Clinic, Zimbabwe. SUBJECTS: All
      registered patients with systemic connective tissue diseases. MAIN OUTCOME
      MEASURES: Numbers of patients, laboratory and clinical features of
      undifferentiated overlapping connective tissue disease. RESULTS: The distribution
      for those who satisfied internationally accepted criteria for
      classification/diagnosis were: 48(52.8pc) rheumatoid arthritis (RA), 17(18.7pc)
      systemic lupus erythematosus (SLE), 10(11pc) juvenile chronic arthritis (JCA),
      four (4.4pc) polymyositis/dermatomyositis (PMD) and 11 (12.1pc) overlapping
      connective tissue disease (overlap) and one unclassified disease. No pure
      progressive systemic (PSS) was registered. Among the overlap patients, five had
      SLE-RA, three SLE-PSS and one each for SLE-RA-PSS, RA-PSS and SLE-PDM overlapping
      clinical features respectively. In two patients with SLE-PSS, the criteria of
      each of the individual connective tissue disease were satisfied. Similarly, in
      one patient with SLE-RA and another with RA-PSS features, the criteria of
      individual disease were also satisfied. CONCLUSION: In undifferentiated
      overlapping connective tissue diseases-overlaps occur in tropical Africa, the SLE
      RA overlapping features predominate and are moderately severe diseases.

PMID- 8870314
TI  - Ethnic differences of renin-sodium profile and renal prostaglandins in the
      pathogenesis of systemic arterial hypertension.
AB  - OBJECTIVE: To compare renin-sodium profile and renal prostaglandins (PGs) of
      Black normotensive and hypertensive patients, with the same parameters of
      Caucasian normotensives and hypertensives, e.g. to reveal some of the ethnic
      differences in the pathogenesis of systemic (essential) hypertension. SUBJECTS:
      27 Black Zimbabwean normotensive and 27 hypertensive patients were matched by
      age, sex and number to Caucasian normotensives and hypertensives (systolic blood
      pressure > 160 mm Hg or diastolic blood pressure > 95 mm Hg, or both). All were
      examined during two protocols producing sodium depletion (less than 40 mmol
      sodium diet/day) for five days, followed by sodium loading (300 mmol sodium
      diet/day) for another five days. Changes in plasma renin activity (PRA), urinary
      aldosterone (Aldo), prostaglandin E2(PGE2) and prostaglandin F2 alpha (PGF2
      alpha) excretions were simultaneously assessed by radioimmunoassay. RESULTS:
      Compared to caucasians the Blacks showed similar basal aldosterone and Na+
      excretion but significant Na+ retention (30pc) during Na+ loading. Their basal
      PRA was lower (32pc) and poorly responding to sodium depletion/loading. They had
      suppressed PG synthesis, the PGE2/PGF2 ratio being significantly decreased 11pc.
      Renin profiles, obtained by plotting PRA against urinary Na+ excretion showed
      prevalence of low renin hypertension (62pc) in Black patients. All Caucasian
      patients had normal renin hypertension. At basal level the Black hypertensives
      had suppressed synthesis of vasodilator PGF2/PGF2 alpha ratio by 32pc. This
      finding was in accordance with their low renin hypertension. During sodium
      depletion the PGs excretion was increased in both hypertensive groups. The
      opposite effect was found during sodium loading. CONCLUSION: This study shows
      ethnic differences in renin-sodium profile and renal PG synthesis, during changes
      in dietary sodium. It addresses an old medical controversy about the usefulness
      of renin profiling in identifying hypertensive patients who are at increased risk
      for heart attack (Whites with normal/high renin hypertension) or increased risk
      of stroke (Blacks with low renin, sodium mediated hypertension).

PMID- 8870315
TI  - Perinatal mortality in an institution where nurse aides conduct deliveries, Nkayi
      District, Zimbabwe.
AB  - OBJECTIVE: To evaluate the perinatal mortality and describe the effects of nurse
      aide conducted deliveries on it at Mbuma hospital, Nkayi District, an institution
      where nurse aides conduct deliveries. DESIGN: Retrospective descriptive study
      based on review of maternal records from January 1992 to December 1994. SETTING:
      Mission hospital situated in a rural area. MAIN OUTCOME MEASURES: The training
      which the health worker who conducted the delivery had and the pregnancy
      outcomes. RESULTS: 1459 deliveries were conducted and of these 824 (57pc) were
      conducted by nurse aides. The perinatal mortality of the nurse aide conducted
      deliveries was five per 1000 births and that of the trained staff was 57 per 1000
      births. CONCLUSIONS: Nurse aides conducted more than half the total deliveries at
      the hospital. The hospital referral system, where normal deliveries are conducted
      by nurse aides while primigravidas and complicated cases are conducted by trained
      staff is working well as supported by the low perinatal mortality of the nurse
      aide conducted deliveries.

PMID- 8870316
TI  - Hospitalized dysentery cases during an outbreak of Shigella dysenteriae type I:
      Ndanga District Hospital, Zimbabwe.
AB  - OBJECTIVE: To describe the characteristics of patients admitted with bloody
      diarrhoea; to assess clinical management; and to identify organisms isolated in
      laboratories and their antimicrobial susceptibility pattern. DESIGN: This was a
      retrospective study which used data from case files of patients admitted for
      dysentery at Ndanga District Hospital. The three admission registers from the
      hospitals male, female and paediatric wards were examined for patients with
      dysentery as their admitting diagnosis from December 1993 to February 1994. Using
      case file numbers from the admission registers, we retrieved case files from the
      records office. SETTING: Ndanga District Hospital in Zaka, Masvingo Province,
      Zimbabwe. SUBJECTS: All patients admitted for dysentery at Ndanga District
      Hospital. MAIN OUTCOME MEASURES: Patients sex, age, clinical presentation,
      complications, drugs given, culture results, and antimicrobial susceptibility,
      duration of stay and outcome. RESULTS: The peak admission period was the last
      week of January, during which 17 patients were admitted with bloody diarrhoea.
      The age distribution of cases was bimodal, children less than five and those 15
      to 29 being most likely to be hospitalized; 52pc of the patients were females.
      Signs and symptoms recorded were bloody diarrhoea 100pc, abdominal pain 45pc,
      dehydration 38pc, fever 34pc, vomiting 26pc, loss of appetite 20pc, weight loss
      17pc and anaemia 5pc. Shigella dysenteriae type 1 (SD1) was isolated in 80pc of
      the 58 stools examined. Most cases were treated with kanamycin
      (67pc),nitrofurantion (61pc), and metronidazole (43pc). The average number of
      antibiotics given per patient was 2.3. Seventeen cases developed complications
      and four patients died, one each with renal failure, haemolytic uraemic syndrome,
      and severe anaemia. The other patient who died had developed rectal prolapse.
      CONCLUSIONS: 80pc of the patients in the study received multiple antibiotics. The
      most frequently used drugs were kanamycin and nitrofurantion, yet neither of
      these drugs has been shown to be effective in treating dysentery. While the
      organisms were largely sensitive to nalidixic acid, little of that was
      prescribed, almost certainly because it was not available until late in the study
      period. There is need for adherence to the Ministry's recommended dysentery
      treatment guideline: prompt treatment with an effective antimicrobial to which
      the organism has been recently shown to be sensitive, and supportive care and
      prompt referral if complications arise.

PMID- 8870317
TI  - Serum interleukin-1 and granulocyte-macrophage colony-stimulating factor levels
      in protein malnourished patients during acute infection.
AB  - OBJECTIVE: To investigate the response of serum interleukin-1 (IL-1) and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) to infection of
      malnourished patients. DESIGN: Prospective observational study. SETTING:
      Paediatric clinics of Karadeniz Technical University, Faculty of Medicine,
      Trabzon, Turkey. SUBJECTS: 13 protein-depleted (kwashiorkor marasmic
      kwashiorkor), 15 marasmic nutritionally repleted kwashiorkor (NRK), and 12 well
      nourished control subjects. INTERVENTIONS: Clinical and laboratory data, and
      serum IL-1 and GM-CSF levels during acute infections were examined. MAIN OUTCOME
      MEASURES: White blood cell count, pc of circulating neutrophils (%PNL), serum
      total protein, albumin (ALB), IL-1 and GM-CSF levels. RESULTS: Fever, pcPNL,
      serum IL-1 and GM-CSF levels of kwashiorkor patients were lower than those of
      marasmic and control patients (p < 0.005). Fever, neutrophil pc(PNLpc), serum IL
      1 and GM-CSF levels of NRK patients during further acute infection were not
      significantly different from those of marasmic and control patients, but higher
      than those of the kwashiorkor patients. Although there were positive correlations
      between serum IL-1 and ALB levels (r = 0.922, p < 0.001), and between serum GM
      CSF and ALB levels (r0.730, p = 0.005) in the kwashiorkor group, there were not
      significant correlations between the same parameters in the other groups (r <
      0.5, p > 0.05). And also, although there was not significant correlations between
      PNL% and IL-1 levels in the kwashiorkor group (r0.312, p = 0.299), there were
      significant positive correlations between the same parameters in the other groups
      (r < 0.5, p > 0.05). However, significant positive correlations were found
      between fever and IL-1 levels, and between IL-1 and GM-CSF levels in all groups
      (r > 0.5, p < 0.05). CONCLUSION: The responses of serum IL-1 and GM-CSF to acute
      infection of kwashiorkor patients are defective, and nutritional-repletion
      therapies restore the production of these cytokines.

PMID- 8870318
TI  - Sero-epidemiology and perception of human brucellosis in Calabar, Nigeria.

PMID- 8870319
TI  - Detection of IgM antibody to Japanese encephalitis virus infection by enzyme
      linked immunosorbent assay (ELISA).
AB  - BACKGROUND: Japanese encephalitis (JE) is an important infectious disease in
      Taiwan, with reported cases observed all the year around. Laboratory tests for JE
      consist mainly of hemagglutination inhibition (HI) test and neutralization test
      (NT). Commercialized enzyme-linked immunosorbent assay (ELISA) kits for detection
      of JE-IgM are still not available. Therefore an attempt has been made to develop
      a sensitive and rapid ELISA for detection of the IgM antibody to JE to serve as
      an indication of recent Japanese encephalitis virus infection. METHODS: Both
      positive and negative JE serum specimens, confirmed by HI test, were checked for
      IgM antibody to JE by ELISA. The optimum concentration of biotin-IgG and avidin
      horse-radish peroxidase conjugate used in MAC-ELISA were 1/2000 and 1/ 15000,
      respectively. RESULTS: From 1987 to 1989, 118 paired serum specimens of HI
      confirmed JE patients were tested for JE-IgM by ELISA. The positive rate of JE
      IgM was 65.7% (25/38), 73.9% (17/23), 93.5% (29/31) and 88.8% (8/9) for the
      consecutive first to fourth weeks after onset of the disease. The JE-IgM antibody
      of 17 serum specimens collected from the 5th to the 10th week after onset of the
      disease were 100% detected. In addition, among the 13 HI-confirmed JE cases
      occurring in 1994, 84.6% of the acute phase serum specimens demonstrated the JE
      IgM antibody. CONCLUSIONS: About 65.7% of the JE-IgM of the acute serum specimens
      collected within one week after onset of the disease were detected. The JE-IgM
      positive rate elevated as the days from disease onset increased. Therefore the
      appearance of JE-IgM could be used as an indication of recent JEV infection to
      serve as a rapid laboratory diagnostic tool.

PMID- 8870320
TI  - Clinical response of tuberculous pericarditis to medical treatment: a
      retrospective survey.
AB  - BACKGROUND: The prevalence of tuberculosis has declined with advanced
      antituberculous chemotherapy. However, the occurrence of subsequent constrictive
      pericarditis in tuberculosis has not reduced. Clinical progress of tuberculous
      pericarditis was investigated in patients receiving antituberculous chemotherapy.
      METHODS: Thirteen patients with tuberculous pericarditis (11 men and 2 women aged
      14 to 86 years [mean 60.0 +/- 17.0]), treated initially with antituberculous
      medications were analyzed. All patients underwent pericardiocentesis on admission
      following echocardiography. RESULTS: Dyspnea was the most common clinical
      pictures. Bloody effusion fluids were noted in 10 patients. Moreover, the
      lymphocytic fluids were present in 78% of all patients. The neutrophilic fluids
      tended to have a bloody color, and there was progress to constrictive
      pericarditis even for those on anti-tuberculous chemotherapy. Five patients with
      subsequent constrictive pericarditis received pericardiectomy within 3.5 months
      of admission. Three of them received pericardiectomy later, despite pericardial
      window procedure. CONCLUSIONS: Follow-up by echocardiogram is necessary within
      three months after commencing medical treatment because of the high incidence of
      progression constrictive pericarditis despite aggressive medical treatment.
      Pericardiectomy seems to be the only solution to the catastrophic outcome of
      constrictive pericarditis.

PMID- 8870321
TI  - Adenomyomatosis of the gallbladder.
AB  - BACKGROUND: Adenomyomatosis of the gallbladder in Chinese patients has rarely
      been analyzed. METHODS: The clinical, radiological and pathological features of
      18 patients with histologically-proven adenomyomatosis, collected during a 5-year
      period, were retrospectively analyzed. RESULTS: According to the extent and site
      of involvement, adenomyomatosis of the gallbladder was conventionally classified
      into three types: localized, generalized and segmental. In our series, the
      disease was localized in 17 patients (15 in the fundus and 2 in the neck),
      generalized in one patient and segmental in none. Only 5 patients showed
      sonographic features correlative to pathologic findings, and 2 of them were
      correctly diagnosed before operation. Only mild nonspecific abnormalities of
      liver function test or urine analysis were noted in some patients with
      gallbladder adenomyomatosis. The clinical manifestations were not related to
      coincidental diseases in 11 patients. All these 11 patients, with gallstone in 9
      and without in 2, complained of epigastralgia, right upper quadrant abdominal
      pain or dyspepsia, which relieved all after cholecystectomy. CONCLUSIONS: Some
      patients with adenomyomatosis may be symptomatic and relieved by cholecystectomy.
      In patients with adenomyomatosis of the gallbladder and right upper quadrant pain
      of abdomen without other explanation, cholecystectomy may be considered.
      Infrequent accurate diagnosis in Chinese patients calls for a high suspicion of
      the disease entity in clinical practice.

PMID- 8870322
TI  - Analysis of 109 cases of infective endocarditis in a tertiary care hospital.
AB  - BACKGROUND: Early diagnosis and treatment can benefit the outcome of patients
      with infective endocarditis. The older diagnostic criteria (von Reyn criteria)
      relied upon tissue pathology and blood culture results, but the sensitivity was
      low. A newly proposed criteria, Duke criteria which apply echocardiographic
      findings as a major factor in diagnosis, have shown a better sensitivity in the
      diagnosis of infective endocarditis. METHODS: From 1984 to 1994, 120 episodes of
      endocarditis in 119 patients were reviewed retrospectively. One hundred and nine
      episodes fulfilling the Duke criteria were enrolled. The demographic data,
      antecedent disease, predisposing factors for infective endocarditis including
      systemic disease, prosthetic valve, intravenous drug abuse, dental or surgical
      manipulation, culture results, echocardiographic findings, complications and
      outcome were recorded and analyzed. RESULTS: Sixty-six percent (72/109) was
      definite endocarditis, and 34% (37/109) was possible endocarditis, as categorized
      by Duke criteria. Eleven percent (12/109) of the patients were rejected by von
      Reyn criteria. The common possible predisposing factors were rheumatic heart
      disease, congenital heart disease, mitral valve prolapse, dental manipulation and
      intravenous drug abuse. Both patients with positive blood culture and negative
      blood culture results had one-fourth mortality rate. A notably higher mortality
      rate was found in patients with S. aureus endocarditis as compared with those of
      endocarditis caused by viridans streptococci(44% vs. 8%, p < 0.05). Patients with
      echocardiographic vegetations had a higher mortality rate (32% vs. 11%, p < 0.05)
      and more peripheral or organ embolic events (26% vs. 6%, p < 0.05) than those
      without vegetation. CONCLUSIONS: The Duke criteria are more sensitive than the
      von Reyn criteria for diagnosis of infective endocarditis. S. aureus endocarditis
      carried a higher mortality rate than viridans streptococci endocarditis. The
      present study also indicated that patients with discernible valvular vegetation
      on echocardiogram had a high mortality rate and occurrence of peripheral or organ
      embolic events. However, there was no statistical significance in the development
      of congestive heart failure and CNS complications between the patients with and
      without vegetation.

PMID- 8870323
TI  - Complications in surgical treatment of undisplaced femoral neck fracture.
AB  - BACKGROUND: Percutaneous Knowles' pinning is a well accepted treatment of
      undisplaced femoral neck fracture, but there are some complications that have
      seldom been discussed. METHODS: One hundred and eighty two patients with
      undisplaced femoral neck fractures, at a mean age of 67 years, were treated by
      percutaneous Knowles' pinning between 1983 to 1989, and followed for an average
      of 102 months. The clinical results and complications were evaluated. The data
      were collected on the basis of age and bone density. Student's t-test was used to
      evaluate the significance of the results. RESULTS: The mean union time was 20
      weeks. In all the patients, 85.8% had good results, 3.8% patients had acceptable
      results and 10.4% patients had poor results. Old age (> or = 65 years) and
      osteoporosis (Singh index < or = 3) were two factors of the poor result. Thirty
      two cases (17.6%) developed complications. The incidence of nonunion or implant
      problems was apparently higher in the older or osteoporosis group, but avascular
      necrosis of femoral head correlated little with old age or osteoporosis.
      CONCLUSIONS: Although percutaneous Knowles' pinning is simple, safe, economic and
      reasonably effective for the treatment of undisplaced femoral neck fractures, we
      should pay more attention to the uncooperative, old, and osteoporotic patients.

PMID- 8870324
TI  - Whole body radiation exposure with gamma unit radiosurgery.
AB  - BACKGROUND: Stereotactic radiosurgery is the use of external radiation in
      association with a stereotactic device to precisely locate and destroy
      inaccessible deep-seated lesions within the brain in a single treatment session.
      Very little attention has been paid to the extracranial sites of radiation
      exposure measurements. This study evaluates the extracranial absorbed dose due to
      leakage and scattered radiation of the Gamma Unit used in radiosurgery. METHODS:
      The absorbed doses were measured with thermoluminescent dosimetry (TLDs). Single
      and multiple Gamma Unit treatment with the 18mm collimator helmet was given and a
      Rando tissue equivalent phantom was in place to simulate a patient treatment.
      TLDs were placed on the phantom to measure the absorbed doses by the organs at
      risk. Two TLD chips were placed at each of the following organs: eye, thyroid,
      sternum and gonads. The irradiated TLDs were read with a Vinten TLD system 654D.
      The TLD factor was determined by irradiating TLDs with a cobalt-60 teletherapy
      unit of a known dose of radiation. RESULTS: The average maximum target absorbed
      dose was 30 Gy. The measured absorbed dose in selected organs from Gamma Unit
      radiosurgery with one or more isocenters was 21-53 cGy for the eye, 4-8 cGy for
      the thyroid, 3-4 cGy for the sternum and 2-3 cGy for the gonads. The dose to
      extracranial sites increased with the number of isocenters. The radiation dose to
      extracranial sites became much more substantial when multiple isocenters were
      used. CONCLUSIONS: The potential risk of radiation exposure is radiation induced
      tumors. No cases have been reported in patients treated with Gamma Unit
      radiosurgery. Given the benefit of Gamma Unit treatment, the clinical
      significance of these doses is minimal.

PMID- 8870325
TI  - Psychotic symptoms in psychiatric inpatients with dementia of the Alzheimer and
      vascular types.
AB  - BACKGROUND: Demented patients often manifest psychotic symptoms including
      delusion, hallucination and misidentification. This report attempts to describe
      the frequencies and characteristics of such symptoms in psychiatric inpatients
      with dementia, and to identify the characteristics of dementia with and without
      psychotic symptoms. METHODS: The study included 78 demented patients who were
      consecutively admitted to the psychiatric ward. Their psychotic symptoms were
      obtained from semistructured interview and the assessment using BEHAVE AD.
      Delusion and hallucination were rated as "present" if the descriptions were
      consistent with the definition of Diagnostic and Statistical Manual of Mental
      Disorders (DSM-III-R). Misidentification was defined individually. RESULTS: There
      were 54 patients with DAT and 24 patients with VD. The frequency of psychotic
      symptoms in DAT and VD was 71.8%. The frequency of delusion in DAT and VD was
      59.0%, misidentification, 33.3% and hallucination, 25.6%. Demented patients with
      psychotic symptoms were older (p = 0.037) than those without psychotic symptoms.
      CONCLUSIONS: Psychotic symptoms are common in psychiatric inpatients with DAT and
      VD, the most common being delusional. Delusion of theft is the most common one.
      Demented patients with psychotic symptoms were older than those without.

PMID- 8870326
TI  - Premedication with diclofenac and prednisolone to prevent postoperative pain and
      swelling after third molar removal.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and steroid are able to
      effectively reduce the postoperative sequelae after impacted third molar removal.
      However, few studies have evaluated the activity of the combined effects of these
      two drugs. The purpose of this study was to evaluate whether a single dose of
      prednisolone, taken orally before operation, would increase the effects of
      diclofenac in preventing pain and swelling after surgical removal of impacted
      third molars. METHODS: Thirty healthy patients requiring surgical removal of four
      third molars were randomly assigned to two groups. In group A, patients were
      preoperatively given 50 mg of either diclofenac or placebo when impacted teeth
      were removed on each side. In group B, in addition to 50 mg of diclofenac, 10 mg
      of prednisolone or placebo was administered. Postoperative pain, swelling and
      range of mouth opening were recorded. RESULTS: Preoperative administration of 50
      mg of diclofenac could relieve pain and swelling more than the placebo.
      Additional 10 mg of prednisolone could further reduce swelling. CONCLUSIONS: The
      combination of diclofenac and prednisolone has a better analgesic and anti
      inflammatory effect.

PMID- 8870327
TI  - Poorly differentiated "insular" carcinoma of the thyroid: a case report.
AB  - Poorly differentiated "insular" carcinoma of the thyroid is a rare type of
      thyroid malignancy, situated morphologically and biologically in an intermediate
      position between well-differentiated (papillary and follicular) and
      undifferentiated (anaplastic) carcinoma. Here we report a case of a 56-year-old
      woman who developed a mass over the left thyroid gland in 1988, and received a
      thyroid operation in 1990 which was reported as benign lesion. Three years later,
      a mass recurred over the right lobe of the thyroid, and another thyroid operation
      was performed. The pathological report was medullary carcinoma. Four months
      later, recurrent mass over the right thyroid bed developed. Fine-needle
      aspiration biopsy of the mass showed moderately high cellularity with moderate
      pleomorphism, and multinucleated giant cells. Distinct cytoplasmic blue granules
      were also found in Liu's stain. She received total thyroidectomy and right neck
      radical dissection. Pathology examination showed well-defined nests of tumor
      cells ('insulae'), and immunohistochemical study showed positive stain for
      calcitonin. Pathologic diagnosis was poorly differentiated "insular" carcinoma of
      the thyroid. Four months after operation, recurrent neck mass over the
      suprasternal notch developed. Computerized tomography of neck and chest showed
      tumor mass over left thyroid bed with extension to anterior mediastinum. Whole
      body 131I scan showed mediastinum involvement and multiple bony metastases.
      Ablative 131I treatments (150 mCi and 200 mCi) were given twice, but in vain. The
      patient died 14 months after her last operation.

PMID- 8870328
TI  - Obstructive jaundice caused by calcified portal venous thrombosis: a case report.
AB  - One case of bile duct obstruction because of calcified thrombosis of the portal
      vein is described. The patient had received splenectomy 20 years previously. He
      was admitted for fever, right upper abdominal pain and jaundice. The initial
      sonography and computed tomography showed dilatation of bilateral intrahepatic
      ducts and common bile duct with adjacent calcified portal vein mimicking common
      bile duct stones. Endoscopic retrograde cholangio-pancreatography showed external
      compression of the common bile duct by the calcified portal vein. Because of the
      patient's poor liver condition, biliary endoprosthesis was performed to relieve
      obstruction. This was an indication that the possibility of portal venous
      thrombosis should be included in the differential diagnosis of patients with
      obstructive jaundice who had previously received splenectomy.

PMID- 8870329
TI  - Non-small cell lung cancer with testicular metastasis: a case report.
AB  - A 51-year-old man was diagnosed to have non-small cell lung cancer, right middle
      lobe, with multiple bony metastasis. Systemic chemotherapy with the regimens of
      cisplatin plus etoposide was administered. A 2 x 2.5 cm firm nodule in the right
      testis was incidentally found two weeks after the first course of chemotherapy.
      Transinguinal right radical orchiectomy was performed. Pathologic examination
      revealed a picture similar to his lung cancer. Secondary carcinoma of the testis
      is extremely rare. The relevant literature about its incidence, clinical
      manifestations, sources of primary tumor and routes of metastasis are reviewed.

PMID- 8870330
TI  - Systemic lupus erythematosus with intussusception: a case report.
AB  - A 19-year-old male with systemic lupus erythematosus, had initially presented
      three years previous by malar rash and nephritis. In the past 2 weeks, he
      experienced bloody diarrhea and lower abdominal pain. Intussusceptions of the
      distal to the terminal ileum, terminal ileum to cecum and cecum to ascending
      colon were proved via exploratory laparotomy. Mesenteric lymphadenopathy was
      thought to be the leading cause. This is the second case of systemic lupus
      erythematosus with intussusception described in the literature.

PMID- 8870331
TI  - Myasthenia gravis complicated with hyperthyroidism, thymoma and serological
      evidence of systemic lupus erythematosus: a case report.
AB  - A 55-year-old woman with a several-decade history of thyroid goiter is presented
      here as a case of myasthenia gravis complicated with hyperthyroidism and thymoma
      with serological evidence of systemic lupus erythematous (SLE). She had had right
      eyelid ptosis since July 1992, with a positive tensilon test. The acetylcholine
      receptor antibody titer was 4.01 nmol/L. A thyroid function test revealed T3: 162
      ngidl, T4: 14.98 micrograms/dl, TSH:0.09 microIU/ml and positive anti-microsomal
      antibody (1:400). An MRI of the chest showed a thymoma in the left thymus. Other
      autoantibody screenings include ANA (1:320, speckled pattern) and anti-ds DNA (+)
      suggesting a serological association with SLE. After three courses of
      plasmapheresis, she received an extended maximal thymomectomy and a subtotal
      thyroidectomy. She was then treated with prednisolone, Mestinon, Eltroxin and
      discharged without complications. The coexistence of myasthenia gravis,
      hyperthyroidism, thymoma and a serological evidence of SLE have not previously
      been documented in the literature.

PMID- 8870332
TI  - Urinary bladder endometriosis: a report of two cases.
AB  - Endometriosis of the urinary tract is uncommon, and the most common site of
      involvement is urinary bladder. Two cases of endometriosis of urinary bladder are
      presented. The first patient, a 39-year-old woman, complained of dysuria during
      menstruation and the other 37-year-old woman suffered from intermittent gross
      hematuria. Pre-operative examinations included ultrasonography, computed
      tomography and cystoscopic biopsy. Case 1 was in premenopausal status, but the
      serum estrogen level of case 2 was in postmenopausal status because she was given
      no exogenous estrogen after previous bilateral salpingo-oophorectomy.
      Endometriosis of urinary bladder rarely occurs in postmenopausal woman without
      exogenous estrogen replacement. Case 1 received danazole treatment after
      transurethral resection of bladder tumor and case 2 received partial cystectomy
      after transurethral resection of bladder tumor. The patients were followed 36 and
      4 months, respectively, and the symptoms kept improving during this period.

PMID- 8870333
TI  - Can medicine serve both humanity and the bottom line?

PMID- 8870334
TI  - The different faces of thyrotoxicosis.

PMID- 8870335
TI  - Contemporary issues in cost-effective drug therapy.

PMID- 8870336
TI  - Interpreting serologic tests for hepatitis C virus infection: balancing cost and
      clarity.
AB  - Although progress has been made toward developing a cheap and accurate method to
      diagnose hepatitis C virus (HCV) infection, current screening tests have an
      unacceptably high false-positive rate. Newer tests are more accurate, but also
      more costly. This paper outlines an approach for interpreting and using these
      different tests. The second-generation enzyme-linked immunosorbent assay (ELISA)
      for HCV antibodies, the current screening test for HCV infection, has a
      sensitivity of approximately 90% but a low specificity. Persons with risk factors
      for HCV infection, elevated aminotransferase levels, and a positive ELISA result
      most likely have HCV infection. Confirmatory testing with a recombinant
      immunoblot assay adds considerably to the cost of diagnosis and should only be
      used to confirm HCV infection in ELISA-positive patients at low risk or with
      conditions such as hyperglobulinemia that promote false-positive reactivity.
      Polymerase chain reaction (PCR) testing is the most sensitive and accurate method
      of diagnosing HCV infection, but its cost limits its use. PCR testing should be
      reserved for cases of diagnostic uncertainty, evaluation of possible acute
      hepatitis C, patients with normal serum aminotransferase levels and anti-HCV
      antibodies, and patients about to undergo interferon therapy.

PMID- 8870337
TI  - Prevention of insulin-dependent diabetes mellitus: an overview of three trials.
AB  - Genetic, immune, and metabolic testing can reveal a person's risk of developing
      insulin-dependent diabetes mellitus (IDDM), and three large clinical trials are
      planned or underway to see if interventions can prevent IDDM in persons at risk.
      Researchers in diabetes prevention trials are screening first- and second-degree
      relatives of probands with IDDM for islet-cell antibodies. In the Cow's Milk
      Avoidance Trial, infant siblings of probands with IDDM will be randomized to
      receive either a baby formula containing a non-antigenic protein hydrolyzate or a
      standard cow's milk-based formula. The Diabetes Prevention Trial-Type I is
      randomly assigning subjects at high risk (more than a 50% probability of
      developing IDDM) to either receive insulin injections or undergo observation
      alone; subjects at intermediate risk (25% to 50%) will receive either oral
      insulin or placebo. In the European Nicotinamide Diabetes Intervention Trial,
      subjects receive either nicotinamide or placebo. If any of these trials show that
      IDDM can be prevented, then large-scale screening of children for IDDM risk
      factors may prove beneficial.

PMID- 8870338
TI  - Preventive cardiology: whose job is it? Who will pay for it? What is the best
      strategy?

PMID- 8870339
TI  - Strategies for managing atrial fibrillation.
AB  - The limitations of current therapies for atrial fibrillation are forcing a
      rethinking of how they should be used. Questions are being raised about the use
      of antiarrhythmic drugs, and new nonpharmacologic procedures are promising
      alternatives. Most patients with atrial fibrillation still require warfarin
      therapy, but some low-risk patients can forego it. Sinus rhythm spontaneously
      returns within the first 24 hours in almost half of cases of new atrial
      fibrillation. Patients with hemodynamic instability due to new-onset atrial
      fibrillation should proceed directly to electrical cardioversion. Warfarin
      therapy to maintain an International Normalized Ratio (INR) of 2.0 to 3.0 is
      currently recommended for all patients with atrial fibrillation with no
      contraindications to it, except for patients younger than 60 years with lone
      atrial fibrillation, in whom the risk of stroke is low. Certain antiarrhythmic
      drugs should be avoided in patients with congestive heart failure, in whom the
      risks may exceed the benefits. The maze procedure is emerging as an option to
      restore and maintain sinus rhythm. Radiofrequency atrioventricular node ablation
      and modification hold promise as options to control the ventricular rate without
      drugs.

PMID- 8870340
TI  - Preoperative autologous blood donation: clinical, economic, and ethical issues.
AB  - Many patients are donating their own blood before surgery to avoid blood-borne
      infections, often on the advice of their physicians. But autologous blood
      transfusion, while safer than allogeneic transfusion, is not completely risk
      free. It is also expensive, its benefits are difficult to assess, and its
      increasing popularity raises many difficult ethical issues, such as whether the
      benefit of allogeneic transfusion supports its additional expense. Record
      keeping, collection, and transfusion errors are occasional risks of autologous
      transfusions. In addition, risks associated with blood donation, from mild
      dizziness to precipitation of angina, should be considered when high-risk
      patients are referred for autologous collection. Only approximately half of
      autologous units collected are actually used, and the cost per quality-adjusted
      year of life saved may be as high as $1 million, depending on the type of
      surgical procedure. Although recombinant human erythropoietin can stimulate red
      blood cell production before autologous donation and decrease the need for
      transfusion, it is not clear whether this strategy, which can cost thousands of
      dollars per patient, will be cost-effective. Perioperative hemodilution may
      become an important component in efforts to reduce patient exposure to allogeneic
      blood, but its use remains controversial.

PMID- 8870341
TI  - What does tumor shrinkage mean to the patient receiving chemotherapy?

PMID- 8870342
TI  - Health quality data.

PMID- 8870343
TI  - Surveillance of Creutzfeldt-Jakob disease.

PMID- 8870344
TI  - Distance education in nursing. Adapting courses for distance education.

PMID- 8870345
TI  - Computer-assisted management of primary open-angle glaucoma. Knowledge
      acquisition and prototype testing.
AB  - Primary open-angle glaucoma is a common disease afflicting 1% to 2% of people
      older than 50 years of age. The care of patients with glaucoma is a subject of
      debate because the disease is incompletely understood. The diagnosis relies on a
      number of examinations, many of them performed by ophthalmic nurses, and the care
      of patients with glaucoma has become one of the main tasks for ophthalmic nurses
      in Sweden. This study describes a knowledge-based system for decision support in
      glaucoma management, which uses seven data elements about the patient to arrive
      at one of 25 different recommendations for appropriate action. In 267 patient
      visits to five different eye clinics, the program recommendations were compared
      with the actual decisions made by the responsible physician. The concordance was
      92% to 100% when policy differences among the clinics were taken into account.
      The program appears to provide substantial decision support in the management of
      primary open-angle glaucoma. The program's ability to support the ophthalmic
      nurses in the care of patients with open-angle glaucoma is being evaluated.

PMID- 8870346
TI  - Computerized NCLEX-RN preparation programs. A comparative review.
AB  - Nursing faculty and students, as well as schools of nursing, are concerned about
      maintaining or improving pass rates on the National Council Licensure Examination
      for Registered Nurses (NCLEX-RN). This article offers a comparative review of
      eight computerized NCLEX-RN preparation programs: Compass RN; Health Education
      Systems, Inc. (HESI) Assess Test; NLN-CAT-RN Pharmacology Test; Meds,
      incorporated Comprehensive Q & A; Mosby's NCLEX Review; Medi-Sim Computer
      Assisted Preparation for NCLEX-RN; Preparing for NCLEX-RN CAT; and NLN-CAT
      Practice RN. Criteria for evaluating these programs include program design
      features, types of questions and feedback, performance reports, screen design,
      ease of use, technical support and documentation, warranty and upgrade policy,
      and price. Issues associated with using NCLEX-RN preparation programs also are
      discussed.

PMID- 8870347
TI  - Multimedia courseware. Transforming the classroom.
AB  - This article describes a project that integrates faculty-developed computer
      courseware into a baccalaureate curriculum. The courseware was implemented as a
      teaching-learning strategy to enhance mastery of content and assist in
      development of decision-making skills. Curriculum, course, and unit objectives
      served as the foundation for the computer courseware lessons. The courseware is
      produced by a design team of six faculty. Computer lessons are interactive and
      actively involve students in the learning process. Students in six of eight
      clinical nursing courses are using faculty-developed courseware.

PMID- 8870348
TI  - Thermal application reduces the duration of stage transition in dysphagia after
      stroke.
AB  - The present study had two purposes. The first was to provide variability data on
      objectively measured durational parameters of swallowing as accomplished by
      dysphagic patients secondary to stroke. The second was to examine the short-term
      effects of thermal application on these same durational measures. The study
      employed a cross-over design with each dysphagic stroke subject swallowing 10
      times in both untreated and treated conditions. Two findings emerged: (1)
      swallowing durations in the 22 dysphagic stroke subjects were highly variable
      within and across subjects and have distributions that were nonnormal with
      nonhomogeneous variances; (2) thermal application reduced duration of stage
      transition (DST) and total swallow duration (TSD). Implications of these findings
      are discussed.

PMID- 8870349
TI  - The innervation of the human upper esophageal sphincter.
AB  - The neuroanatomy and physiology of the human upper esophageal sphincter (UES) has
      long been controversial. As a result, there has been little progress in
      diagnosing and treating dysphagias involving this area. In this study, three
      specimens of the UES obtained from human autopsies were examined by Sihler's
      stain. This stain clears soft tissue while counterstaining the nerves, thereby
      allowing nerve supply to each muscle of the UES to be demonstrated. It was found
      that the nerve supply to each component of the UES is substantially different.
      The inferior pharyngeal constrictor (IPC) is supplied by a dense linear plexus
      which is about 1.0-1.5 cm wide and 10 cm long and located about 1.5 cm lateral to
      the attachment of the IPC on the thyroid lamina. The cricopharyngeal (CP) muscle
      receives its innervation from below via the recurrent laryngeal nerve (RLN) and
      from above via the pharyngeal plexus. Neural connections between the RLN and the
      pharyngeal plexus were observed. Finally, the upper esophagus (UE) is innervated
      by the RLN. The innervation pattern of each component of the UES suggests
      functional differences between these muscles. These observations help clarify the
      innervation of the UES. Accurate knowledge of the neuroanatomy of the UES is
      necessary for advances in diagnosis and treatment of pharyngeal dysphagia.

PMID- 8870350
TI  - A new application for electropalatography: swallowing.
AB  - Electropalatography (EPG) has been applied to linguistic research and speech
      pathology. This study evaluated whether EPG could provide useful information on
      swallow-related tongue action. Specifically, the investigation focused on the
      quantification of tongue-palate contact patterns for swallowing and on the
      effects of bolus volume and consistency. Five normal subjects were tested during
      swallows of 5 and 30 ml of water, 5 and 30 ml of gelatin, and saliva. By
      segmenting the EPG time-motion sequences into four stages (prepropulsion,
      propulsion, full contact, withdrawal) and compartmentalizing the palate into six
      bins (front, central, back, lateral, medial, midline), temporal and spatial
      characteristics of deglutitive tongue-palate contact were revealed. Significant
      differences (p < 0.01) were found in contact timing across bolus sizes and
      consistencies for the propulsion and full contact stages. Water was propelled
      faster than gelatin. and 30-ml gelatin faster than 5-ml gelatin. Dry swallows had
      a longer full contact stage than water. Contact patterns, though not
      statistically analyzed at this time, appeared to vary little as a function of
      bolus properties. Our findings suggest potential value in using EPG to
      investigate the timing and patterning of abnormal tongue movements associated
      with disordered swallowing.

PMID- 8870352
TI  - Ambulatory esophageal pH monitoring in patients with motility disorders.

PMID- 8870351
TI  - Reproducibility of ambulatory esophageal pH monitoring in the aperistaltic
      esophagus.
AB  - The reproducibility of ambulatory 24-h esophageal pH monitoring was evaluated in
      16 consecutive patients by comparing the difference in two consecutive 24-h
      periods. The study group included 8 patients with scleroderma esophagus and 8
      treated achalasia patients. The amount of reflux was expressed as the percentage
      of time the pH was < 4.0. Both groups demonstrated excellent intrapatient
      reproducibility overall: 96% in scleroderma patients and 95% in those patients
      with achalasia. The least concordance was found in the lengths of the longest
      reflux events-70% when supine in scleroderma patients and 59% when upright in
      patients with achalasia. There was no significant difference (p > 0.05) between
      day 1 and day 2 for either group of patients for any of the elements studied.
      These results indicate that intrapatient variability of gastroesophageal reflux
      in patients with scleroderma esophagus and treated patients with achalasia is
      very low and following therapeutic intervention, a high level of confidence can
      be placed in subsequent pH monitoring as an indicator of treatment effect.

PMID- 8870353
TI  - Effect of occlusion of a tracheotomy tube on aspiration.
AB  - The purpose of the present study was to investigate the effect of occlusion of a
      tracheotomy tube on aspiration utilizing fluoroscopy. Twenty consecutive
      tracheotomized patients referred for a modified barium swallow were included.
      Selection criteria were ability to tolerate tracheotomy tube occlusion during the
      modified barium swallow procedure, no surgery of the upper aerodigestive tract
      except tracheotomy, and no history of oropharyngeal cancer or stroke. There was
      100% agreement among 3 independent reviewers on ratings of the presence or
      absence of aspiration. It was found that the occlusion status of the tracheotomy
      tube did not influence the prevalence of aspiration. Nine of 10 (90%) subjects
      who exhibited aspiration were over 65 years of age (mean = 72 years 2 months). No
      trends were observed for bolus consistency, type of tracheotomy tube, or
      presence/absence of a nasogastric tube and ratings of aspiration.

PMID- 8870354
TI  - An electronic device measuring the frequency of spontaneous swallowing: digital
      phagometer.
AB  - A new and portable electronic device called the "Digital Phagometer" is described
      for the time based counting of spontaneous swallowing. This device is composed of
      a piezoelectric sensor and a digital event counter/ recorder which can be
      downloaded to any IBM-compatible PC. The sensor of Digital Phagometer is placed
      and fixed on the coniotomy region between the cricoid and thyroid cartilage. In
      this way, it is capable of sensing each upward and downward movement of the
      larynx produced by spontaneous movement as a function of time. Spontaneous
      swallowing was measured 1-4 h after lunch in 21 normal subjects and 21 patients
      with Parkinson's disease (PD). The mean frequency of spontaneous swallowing was
      0.8 counts/min in PD patients and 1.18 counts/ min in normal subjects (p < 0.05).
      During the intake of 200 ml water, the mean frequency of voluntary swallowing did
      not differ significantly between the two groups (24.6 counts/min in normals vs.
      22.3 counts/min in PD patients), but the time necessary to swallow the same
      volume of water was longer in the PD group.

PMID- 8870355
TI  - Deglutition after supracricoid laryngectomy: compensatory mechanisms and
      sequelae.
AB  - This study is based on the videofluorographic exploration of deglutition in 14
      patients who were treated by supracricoid laryngectomy. The choice of this
      population rests on two criteria: a 1-year postoperative delay, and absence of
      residual deglutition disorders elicited by patient history. Asymptomatic
      aspiration was seen in 6 cases. In the cricohyoidoepiglottopexies (CHEP),
      aspiration occurred uniquely in patients who did not recuperate satisfactorily
      from epiglottic dynamics. The deglutition sequelae are less invalidating relative
      to the cricohyoidopexies (CHP), with a possible recuperation of the dynamic
      sequence of the pharyngeal swallow. On the other hand, in the CHP, a complete
      reorganization of the stepwise sequence of the different neuromuscular events is
      necessary.

PMID- 8870356
TI  - The clinical measurement of swallowing in health and in neurogenic dysphagia.

PMID- 8870357
TI  - The lack of progression of neurologic deficit in survivors of paralytic polio.

PMID- 8870358
TI  - A comment on quantitative assessment of oral and pharyngeal function in
      Parkinson's disease.

PMID- 8870359
TI  - Cerumen and coning candle chicanery.

PMID- 8870360
TI  - Classification of chronic suppurative otitis media: type III.

PMID- 8870361
TI  - Endoscopic view of the suprabullar and retrobullar recesses (sinus lateralis).

PMID- 8870362
TI  - Acute vocal fold hemorrhage with minimal dysphonia.

PMID- 8870363
TI  - Coning candles--an alert for otolaryngologists?

PMID- 8870364
TI  - Continuous quality improvement in otolaryngology.

PMID- 8870365
TI  - Retrolabyrinthine selective posterior root section of the trigeminal nerve for
      the treatment of trigeminal neuralgia.
AB  - Patients frequently consult otolaryngologists for the treatment of trigeminal
      neuralgia. Retrolabyrinthine selective posterior root section of the fifth
      cranial nerve effectively and permanently eliminates pain from areas supplied by
      this nerve without the production of annoying anesthesia dolorosa. The procedure
      is performed by the neurotologist and causes minimum morbidity. The results of
      this surgery in 106 patients are reviewed and demonstrate that the procedure
      provides lasting relief from intractable pain from a variety of conditions whose
      innervation is the Vth cranial nerve as well as trigeminal neuralgia. The
      surgical technique and long-term results are described.

PMID- 8870366
TI  - Powered nasal polypectomy in the office setting.
AB  - The use of powered instrumentation has revolutionized the practice of functional
      endoscopic sinus surgery. We have expanded the role of the instrument to the
      treatment of polypoid disease of the nose within the office setting. We have
      found the technique to be both safe and effective, and to allow thorough
      exenteration of nasal polyps with minimal bleeding and discomfort. We recommend
      the use of the powered device as the primary tool in the surgical treatment of
      nasal polyps in the office.

PMID- 8870367
TI  - The management of post-thyroidectomy hypocalcemia.
AB  - Postoperative hypocalcemia was studied in 40 patients undergoing total
      thyroidectomy for a malignancy or massive goiter. Parameters evaluated included
      serum calcium, phosphate and magnesium levels. All patients exhibited a
      postoperative decline in serum calcium, however, the lowest serum calcium level
      was not seen until 48 hours after surgery. Serum calcium levels returned to
      normal in five to six days after surgery in 37 patients. Five patients required
      calcium supplementation for either symptomatic hypocalcemia or serum calcium
      levels lower than 7.0 mg/dl. Only three of these five patients were discharged
      home on oral calcium supplements. In this series, we discovered that the critical
      period for monitoring of serum calcium was 24 to 96 hours after surgery. If serum
      calcium replacement was not needed in the first 72 hours after surgery, it would
      not be needed during the remainder of the patient's hospital course. In addition,
      we found that serum magnesium levels should also be monitored in the
      postoperative period and corrected if low.

PMID- 8870368
TI  - Cyclic alternating pattern sequences in non-apneic snorers with and without nasal
      dilation.
AB  - A study was conducted to polysomnographically evaluate the effects of external
      nasal dilation on sleep quality in mild snorers by examining the amount of sleep
      fragmentation and cyclic alternating pattern sequences (CAPS) rates. A two-night,
      open-label, one-way crossover polysomnographic evaluation, with and without use
      of an external nasal dilator, was done at the Tri-State Sleep Disorders Center in
      Cincinnati, Ohio. Nine snorers, polysomnographically determined to be free of
      clinically significant levels of obstructive sleep apnea, were studied. CAPS
      rates with nasal dilation were 28.4% as compared to 37.9% without nasal dilation
      (p < 0.05). We conclude that external nasal dilation reduces arousal instability
      in snorers without obstructive sleep apnea.

PMID- 8870369
TI  - Renal clear cell carcinoma appearing as a left neck mass.
AB  - Malignant clear cell tumors of the head and neck are uncommon. Primary tumors may
      arise from the salivary glands, thyroid gland, or parathyroid glands, while
      metastatic tumors most commonly arise from the lungs, kidneys, and female genital
      tract. Renal cell carcinoma is the third most common metastatic tumor to the bone
      and soft tissues of the head and neck. Despite this, there have been few reported
      cases of renal clear cell carcinoma metastases to the neck. Here we report a
      unique case of an otherwise asymptomatic young woman with a left neck mass as the
      first clinical sign of advanced renal clear cell carcinoma.

PMID- 8870370
TI  - Nasal septal necrosis mimicking Wegener's granulomatosis in a cocaine abuser.

PMID- 8870371
TI  - Current therapeutic options for multiple myeloma.

PMID- 8870372
TI  - Overcoming PGP-related multidrug resistance. The cyclosporine derivative SDZ PSC
      833 can abolish the resistance to methoxy-morpholynil-doxorubicin.
AB  - BACKGROUND: The results obtained so far in studies designed to neutralize P
      glycoprotein (PGP)-related multidrug resistance (MDR) by using MDR reversal
      agents, have not yet fulfilled the promise of the experiments which were
      performed in vitro. In order to improve PGP-related MDR neutralization, we tested
      in vitro the activity of the cyclosporine derivative SDZ PSC 833 (PSC) together
      with doxorubicin (DOX) and with two new DOX derivatives named 4' iodo 4' deoxy
      doxorubicin (IODODOX) and methoxy-morpholynil-doxorubicin (MMDOX, FCE 23762)
      using four different human cell lines and their multi-drug resistant variants.
      METHODS: Anthracycline toxicity was evaluated by using the MTT method after a 7
      day culture with continuous exposure to the antitumor drugs with or without the
      addition of PSC. RESULTS: PSC significantly downmodulated the toxicity of all
      three anthracyclines in all the four cell systems. However, despite the great
      increase caused by PSC in the toxicity of DOX and a more modest effect on the
      toxicity of the two DOX derivatives, this MDR reversal agent could only
      completely block the PGP mediated MMDOX resistance whereas DOX refractoriness was
      only decreased. CONCLUSIONS: The combination of MMDOX or IODODOX with PSC 1.6
      microM is more efficient than the combination of DOX plus PSC for the full
      reversion of PGP-mediated drug resistance. Careful clinical studies are required
      to evaluate if these associations can also effectively and safely neutralize MDR
      in vivo.

PMID- 8870373
TI  - Differential expression of BCL-2 oncoprotein and Fas antigen on normal peripheral
      blood and leukemic bone marrow cells. A flow cytometric analysis.
AB  - BACKGROUND: Fas antigen (Ag) has recently been identified as the putative surface
      molecule capable of transducing apoptotic signals into cells. Alterations in the
      expression of proto-oncogene bcl-2 have been implicated in the regulation of
      apoptosis. MATERIALS AND METHODS: By employing a monoclonal antibody to bcl-2
      protein (124 clone) and to Fas Ag (UB2 clone) the expression of these molecules
      was analyzed at flow cytometry on bone marrow (BM) and peripheral blood (PB)
      samples from patients suffering from different lymphoid and myeloid leukemic
      diseases (27 acute non-lymphocytic leukemia [ANLL]; 14 acute lymphocytic leukemia
      [ALL]; 19 B-cell chronic lymphocytic leukemia [CLL]; 2 Ph1+ chronic myeloid
      leukemia [CML]; one CD8+ T-cell chronic lymphoproliferative disorders). Results
      were compared with those observed on normal PB leukocytes and BM B-cell
      precursors from patients with non-neoplastic hematological disorders. RESULTS:
      Fas Ag was constitutively expressed by both monocytes and neutrophils, while
      lymphocytes expressed bcl-2 with no difference between B and T cell subsets.
      Interestingly, bcl-2 expression was always absent on neutrophils. When dealing
      with ANLL patients, a relatively low bcl-2 and high Fas Ag phenotype
      characterized subtypes with granulocytic (M2) or promyelocytic (M3)
      differentiation. This observation was confirmed in a small number of patients for
      whom bcl-2 levels were quantified as antibody binding capacity (ABC) in
      molecules/cell. Leukemic cells from patients with ALL constitutively expressed
      bcl-2, the pattern of this expression being quantitatively lower than that of
      immature B-cell precursors. Finally, high bcl-2 and low Fas Ag expression
      represented a crucial part of the B-cell CLL immunophenotype. CONCLUSIONS:
      Although based on a small number of patient and control samples, our results
      suggest that bcl-2 and Fas Ag are coordinately expressed on normal PB leukocytes.
      Fas Ag is expressed at low levels on B-CLL cells, generally considered long
      surviving cells. The relatively lower bcl-2-expression detected in both M2 and M3
      subtypes may explain, at least in part, the higher remission rates obtained in
      these forms of ANLL than in other less differentiated morphological variants.

PMID- 8870374
TI  - Clinical significance of sIL2R, sCD23, sICAM-1, IL6 and sCD 14 serum levels in B
      cell chronic lymphocytic leukemia.
AB  - BACKGROUND: The aim of the study was to establish the role exerted by some
      soluble factors in B-CLL disease mechanisms. MATERIALS AND METHODS: Serum levels
      of sIL2R, sCD23, sICAM-1, IL6 and sCD14 were detected in 47 B-CLL patients.
      Thirty-seven out of the 47 cases were in advanced/progressive stage, while the
      remaining 10 patients were defined as smouldering B-CLL. Twenty normal controls
      provided the reference values. Serum samples of 24 out 37 advanced/progressive
      cases were measured before and six months after the start of chemotherapy.
      RESULTS: The advanced/progressive patients showed significantly higher levels of
      sIL2R, sICAM-1 and sCD23 as compared to normal subjects. Furthermore, sIL2R,
      sICAM-1 and IL6 values were significantly higher in advanced/progressive B-CLL
      than in smouldering B-CLL patients. A statistically significant difference was
      found between smouldering B-CLL and controls for sCD14 only. sIL2R and sICAM-1
      levels directly correlated with total tumor mass (TTM) score, sCD23 with both TTM
      score and lymphocytosis, and sCD14 with IgG serum values. sIL2R and sCD23 levels
      lowered significantly after chemotherapy, but only sCD23 and TTM variations after
      chemotherapy were closely correlated. CONCLUSIONS: sCD23 may be considered the
      only indicator of tumor mass, while the other soluble factors can be released
      through different mechanisms. In particular, sICAM-1 seems to correlate with the
      ability of the tumor to spread, while the sCD14 increase could indicate a role
      for this soluble factor in preventing infections in B-CLL patients.

PMID- 8870375
TI  - Empirically derived classification of coagulation disorders in 224 patients.
AB  - BACKGROUND: It is not known whether the current molecular classification of blood
      coagulation disorders into severe (0-1%), moderate (1-5%) and mild (5-40% factor
      activity remaining) corresponds to the actual clinical situation or is in the
      patients best interest. METHODS: A questionnaire-based study of 244 patients.
      Principal factor analysis was used to create a set of variables for
      classification, which was performed using K-means algorithm. The main variables
      were use of prophylactic treatment during the last five years and during the last
      12 months, home treatment, bleeding, surgery, antibody inhibitors, use of cold
      medication, pain, use of analgesics, functional disability and physical activity
      level. RESULTS: The first five variables of the main outcome measures loaded to a
      factor reflecting bleeding (bleeding factor) and the last four to a pain factor;
      both factors produced a 3-cluster solution with severe, moderate and mild
      bleeding or pain. Overlap between the molecular, bleeding and pain
      classifications was not extensive. Only 16% of 81 patients with severe
      coagulation factor deficiency had severe musculoskeletal pain and disability.
      Furthermore, only 28.6% of the patients with severe von Willebrand's disease
      actually had a severe bleeding disorder. CONCLUSIONS: Molecular classification
      does not correlate very well with the severity of disease as reflected in
      bleeding and pain. This is due to better prognosis for patients on modern medical
      management. Appropriate patient classification is a basis for defining and
      managing patients' clinical problems.

PMID- 8870376
TI  - Prognosis of chronic myelomonocytic leukemia.
AB  - BACKGROUND: Cytopenia caused by ineffective hematopoiesis and monocyte
      overproduction coexist in CMML, providing grounds for discussion to supporters of
      a dysplastic versus a proliferative identity for CMML. Follow-up information from
      a large series of patients may contribute to clarifying the position of this
      infrequent disease. METHODS: We analyzed data from 77 patients followed in five
      institutions. Thirty-two variables were studied for their influence on survival
      and on progression to acute leukemia by univariate and multivariate analysis. For
      some parameters, we performed a quartile analysis to reveal a possible non
      monotonic influence on survival. RESULTS: Median survival was 17 months.
      Evolution to acute leukemia (ANLL) occurred in 11 patients (14%) within a median
      time of 8 months. Multivariate analysis assigned a poorer prognosis to patients
      presenting with thrombocytopenia, anemia and leukocytosis. Thrombocytopenia and
      the presence of circulating blasts were risk factors for transformation to ANLL,
      while raised serum aspartate transaminase at diagnosis seemed to be associated
      with a lower probability of blastic evolution. The Bournemouth score for CMML
      proved to be a valid tool for predicting survival but not acute transformation.
      CONCLUSIONS: CMML is a severe disease. The prognostic independence of cytopenia
      (anemia, thrombocytopenia) and leukocytosis underlines the coexistence of aspects
      typical of myelodysplastic and myeloproliferative syndromes.

PMID- 8870377
TI  - Allogeneic stem cell transplantation for advanced low-grade lymphoproliferative
      disorders: report of six cases.
AB  - BACKGROUND: Allogeneic stem cell transplantation is being increasingly used to
      treat young patients with poor-prognosis low-grade lymphoproliferative disorders.
      We report our single-center experience. PATIENTS AND METHODS: Six adults (four
      with advanced chronic lymphocytic leukemia, one follicular center cell lymphoma
      and one mantle cell lymphoma) underwent allogeneic stem cell transplantation
      (SCT). Five received bone marrow while one received peripheral blood stem cells.
      Donors were HLA-identical siblings in five cases and an HLA-haploidentical
      sibling in one. The conditioning regimen included in five cases cyclophosphamide,
      TB1 and high-dose chlorambucil, without the latter in the patient with follicular
      lymphoma. RESULTS: Five patients successfully engrafted, while the patient who
      received the haploidentical marrow suffered primary graft failure. There were two
      cases of grade 2 acute GVHD and one limited chronic GVHD. Four patients are alive
      in complete remission (CR) with a follow-up of 17+ to 118+ months. Additionally,
      there is no evidence of residual disease by immunologic and molecular techniques
      in three cases, while one patient has residual disease assessed by molecular
      methods. CONCLUSIONS: These results suggest that allogeneic SCT can achieve
      prolonged remissions in advanced chronic lymphoproliferative disorders.

PMID- 8870378
TI  - Rapid liver failure related to chronic C hepatitis in an HIV seropositive
      hemophilic patient with severe immunodepression.
AB  - We report the case of a young HIV seropositive patient with severe hemophilia A
      who presented rapid liver failure related to his chronic C hepatitis. The patient
      had been receiving factor VIII:C clotting factor concentrates (mean 60,000
      U/year) since 1975. In 1984 alanine aminotransferase presented abnormal levels.
      The CD4 lymphocyte count in 1991 was normal and ultrasonographic scan showed
      normal liver morphology. In 1991 the patient were found to be seropositive for
      HCV antibodies as detected by the ELISA method and confirmed by the RIBA method.
      One year later, a progressive increase in policlonal gamma-globulin and a
      decrease in the CD4+ lymphocyte count to below 500/muL were detected in
      concomitance with ultrasonographic evidence of a progressive increase in the
      longitudinal diameters of the liver and spleen and signs of liver inhomogeneity.
      A significant inverse correlation was observed between the increase in the
      longitudinal diameter of the liver and the decline in albumin levels, and between
      the increase in the longitudinal diameter of the liver and the drop in platelet
      count. Elevated levels of ammonemia, gamma-glutamyl transpeptidase, alkaline
      phosphatase and IgA were detected. Moreover, decreased levels of the C4 and C3
      complement fractions were documented. At this time (1994), esophagogram and
      esophagogastroscopy evidenced varicosities in the lower esophageal section (stage
      F1). The patient died in 1995 March at the age of 29 years of sudden septic shock
      related to Pseudomonas aeruginosa infection.

PMID- 8870379
TI  - Testicular relapse of AML during chronic graft-versus-host disease induced by
      donor leukocyte infusion.
AB  - Treatment options for acute leukemia relapsing after allogeneic BMT include
      conventional chemotherapy or a second transplant; however, results are rather
      discouraging, the first option being associated with poor survival and the second
      with a high mortality rate. More recently, donor leukocyte infusion (DLI) from
      the original donor has been used for relapsed patients in an attempt to induce a
      graft-versus-leukemia (GVL) effect. This procedure is partially devoid of the
      toxicity inherent to a second BMT. At our Institution, a 36-year-old patient with
      biphenotypic AML in second complete remission after relapse following allogeneic
      BMT was treated with peripheral blood stem cell (PBSC)-enriched donor leukocytes,
      obtained after in vivo priming with rhG-CSF. The patient experienced extensive
      cGVHD but developed a testicular relapse while in full hematologic remission.
      After irradiation of the sanctuary site he remains free of disease, still with
      chronic GVHD, 21 months after bone marrow relapse. This case suggests that
      immunologically privileged sites are inaccessible to GVHD/GVL effect. This should
      be considered when planning salvage transplants procedures in patients at risk
      for extramedullary involvement.

PMID- 8870380
TI  - Return to normal values of lipid pattern after effective chemotherapy in acute
      lymphoblastic leukemia.
AB  - In the present work we investigated HDL-C and its subfractions HDL2 and HDL3 as
      well as total cholesterol (TC), triglycerides (TG), LDL-C, VLDL-C,
      apolipoproteins A1 (ApoA1) and B (ApoB) and lipoprotein (a) (Lp(a) in 25 patients
      with newly diagnosed acute lymphocytic leukemia (ALL) before and after induction
      treatment. The mean basal plasma levels of TC, HDL-C and its subfractions, LDL-C,
      and ApoA1 were significantly lower than the mean values observed in normal
      subjects, whereas TG and VLDL-C were significantly higher. The patients (n = 22)
      who achieved complete remission after chemotherapy showed a significant increase
      of TC, HDL-C, HDL2, HDL3, ApoA1 and a significant decrease of TG and VLDL-C.
      These data suggest that ALL patients are characterized by a lipid metabolic
      derangement mainly of HDL and TG-rich lipoproteins, that is reversed by effective
      treatment of disease.

PMID- 8870381
TI  - Achievement and maintenance of complete remission in a patient with acute
      myelogenous leukemia after weekly administration of interleukin-2.
AB  - Several groups have used high doses of interleukin-2 (IL-2), achieving a
      significant rate of responses in patients with acute myelogenous leukemia (AML).
      These results have mainly been observed in AML patients with limited disease
      (bone marrow blasts < 25%), but this therapy is associated with significant
      toxicity which is dose-related. In this report we describe a patient with AML in
      whom conventional chemotherapy had achieved partial remission. This patient
      received subcutaneously intermediate doses of IL-2 (12 x 10(6)/m2/week) and
      achieved complete remission which was maintained for eleven months. The side
      effects of IL-2 were mild. The results of this report document the antileukemic
      effect of IL-2 in AML with limited disease as well as the efficacy of
      subcutaneous maintenance treatment for prolonged periods.

PMID- 8870382
TI  - Lack of efficacy of a double autograft program to prolong survival of chronic
      myelogenous leukemia patients in blastic transformation.
AB  - The prognosis of patients in blast crisis of chronic myelogenous leukemia treated
      with conventional polychemotherapy is extremely poor. Autologous blood stem cell
      transplantation has been proposed by several authors, and the possibility of
      achieving a second chronic phase (CP), albeit very short lived, has been
      reported. In our study, we evaluated the feasibility and efficacy of a double
      sequential autograft program utilizing two different conditioning regimens. Nine
      patients underwent the first autograft, but only three were eligible for the
      second because of one early death, four relapses and one patient who underwent
      mismatched alloBMT. Of the three patients receiving the second graft, we observed
      2 toxic deaths and one relapse six months after transplantation. We conclude that
      our experience with double autograft in this phase of the disease is very
      disappointing. since it was associated with prohibitive toxicity in the absence
      of any advantages in terms of survival for these patients.

PMID- 8870383
TI  - Disseminated Geotrichum capitatum infection with predominant liver involvement in
      a patient with non Hodgkin's lymphoma.
AB  - Geotrichum capitatum is an emerging opportunistic pathogen which causes invasive
      disease in immunocompromized patients. We describe a patient with non Hodgkin's
      lymphoma and disseminated infection by G. capitatum with predominant liver
      involvement, which was proven by repeated positive blood cultures and a liver
      biopsy. Staining liver biopsy demonstrated the presence of hyphal elements
      consistent with G. capitatum. Combined antimycotic treatment with amphotericin B
      and 5-flucytosine did not eradicate the mycotic infection as shown by the
      persistence of liver lesions.

PMID- 8870384
TI  - Peripheral blood stem cell transplantation for the treatment of multiple myeloma:
      biological and clinical implications.

PMID- 8870385
TI  - Circulating ringed sideroblasts in the course of the initial erythremic phase of
      erythroleukemia.

PMID- 8870386
TI  - Erythroid blast crisis of chronic myeloid leukemia.

PMID- 8870387
TI  - Occurrence of cerebellar thrombohemorrhage during all-trans retinoic acid (ATRA)
      therapy in a case of acute promyelocytic leukemia.

PMID- 8870388
TI  - Erythropoietin in myelodysplastic syndromes: durable response in a young patient.

PMID- 8870389
TI  - Viral diseases of livestock in Zambia.
AB  - This review is to provide information on viral diseases of livestock in Zambia.
      The distribution of the diseases as well as the control measures and limited
      research that has been done, are described. Foot and mouth disease (FMD) causes
      serious economic losses in the cattle industry. So far five serotypes (SAT1,
      SAT2, SAT3, O and At of FMD virus have been isolated in Zambia. Other notifiable
      viral diseases are rabies, Rift Valley fever, Lumpy skin disease, African horse
      sickness, bluetongue, African swine fever, Newcastle disease, Marek's disease,
      fowlpox and infectious bursal disease. Based on the reports of clinical and/or
      serological diagnoses, these are widespread in the country, although their
      precise incidence rates are not known. With the establishment of a veterinary
      school equipped with modern diagnostic facilities and the increasing number of
      qualified veterinary personnel, this review would stimulate surveillance study on
      the viral diseases for the ultimate goal of achieving effective disease control
      measures.

PMID- 8870390
TI  - Changes of serum cytokine activities and other parameters in dogs with
      experimentally induced endotoxic shock.
AB  - To study the relationship of changes of cytokines in endotoxic shock, serum tumor
      necrosis factor (TNF), interleukin (IL)-1 and IL-6 like activities, together with
      physiologic and hemodynamic responses, were examined in dogs before and after
      intravenous administration of lipopolysaccharide (LPS) purified from Escherichia
      coli in a dose of 500 micrograms/kg of body weight. The blood endotoxin
      concentration increased significantly at 30 min after LPS administration, and
      maintained high levels for 24 hr. Red blood cell counts; hemoglobin concentration
      and hematocrit values increased at 30 min, and these high values persisted for 24
      hr. The platelet count decreased significantly at 30 min, then showed a tendency
      to recover, but decreased again at 24 hr. Cardiac output, cardiac index and mean
      arterial pressure showed transient, significant decreases at 15 min, and then
      returned to the baseline levels by 24 hr. TNF-like activities increased at 30
      min, while IL-1-like activities did so between 30 and 60 min. The former reached
      the maximal levels at 2 hr and the latter at 1.5 hr. Both activities were then
      hardly detectable from 6 to 24 hr. IL-6-like activities elevated at 1 hr with the
      peak at 1.5 hr, and remained high until 24 hr.

PMID- 8870391
TI  - African swine fever in Zambia: potential financial and production consequences
      for the commercial sector.
AB  - The first officially recorded outbreak of African swine fever (ASF) in Zambia was
      in Eastern province in 1965. The disease now covers almost the whole province and
      is endemic in the indigenous breeds. In 1989, an outbreak of ASF occurred on a
      commercial property in central Zambia for the first time and was eradicated by
      depopulation. In order to examine the justification of the drastic control
      measures and the continued ban on the export of pigs and their products, the
      impact of the outbreak on the affected property as well as the potential
      consequences on the commercial pig sector in the district was assessed in the
      present study. The affected property lost 421,238 Zambian Kwacha (ZK)
      (USf439,965) as a result of the outbreak and control measures. However, the cost
      to the district could have been at least ZK14,917,500 (US$1,415,323) if the
      measures had not been effected. Furthermore, not taking such measures would have
      increased the risk to the entire commercial pig sector along the line of rail in
      urban centers.

PMID- 8870392
TI  - Studies on coproantigen detection for diagnosis of Echinococcus infection in
      definitive hosts.

PMID- 8870393
TI  - The effects of noxious mechanical stimulation on heart rate, mean arterial blood
      pressure and cytotoxic activity of splenic natural killer cells in anesthetized
      rats.

PMID- 8870394
TI  - Extrathymic generation and antigen recognition of IL3-induced CD4-CD8 alpha beta
      T cells.

PMID- 8870395
TI  - Experimental pathological studies on mechanism of abortion caused by equine
      arteritis virus.

PMID- 8870396
TI  - Enhancement of gene expression by Marek's disease virus homologue of the herpes
      simplex virus-1 ICP4.

PMID- 8870397
TI  - Outbreak of severe gastroenteritis in adults and children associated with type G2
      rotavirus. Study Group on Diarrhea of the Instituto Adolfo Lutz.
AB  - An outbreak of severe gastroenteritis affecting 132 adults and children occurred
      in the small city of Mirassol, Sao Paulo, Brazil, in 1992. The outbreak of
      diarrhoeal disease had an abrupt onset and afflicted all age segments of the
      population. Group A rotavirus was the only pathogen associated with the epidemic.
      It was detected in 12 of the 27 (44%) stool specimens analyzed and was identified
      as serotype G2 rotavirus. Severe dehydration was common among adults and older
      children, and 35% of all the notified cases were hospitalized for parenteral
      rehydration. Contamination of the main water supply was the most likely source.

PMID- 8870398
TI  - Understanding of hygiene behaviour and diarrhoea in two villages in Botswana.
AB  - This paper describes a study which took place in two villages in north-east
      district of Botswana from July 1990 through July 1991. Qualitative data
      collection methods were used including: observations, key-informant interviews,
      focus groups, and in-depth interviews. The data were used for understanding and
      interpreting the cultural belief systems regarding specific hygiene behaviours
      and diarrhoea, with emphasis on hand washing. Hand washing was said to occur for
      three main reasons: to remove contamination, for social reasons, and for comfort
      reasons. Sources of dirt on the hands included human blood and faeces. Many
      perceived causes of diarrhoea were identified, including pogwana (dehydration
      associated with sunken anterior fontanelle). Traditional concepts regarding the
      treatment and prevention of diarrhoea were also identified. It is suggested that
      beliefs surrounding hygiene behaviour and diarrhoea should be incorporated into
      health education programmes.

PMID- 8870399
TI  - Prevalence of Cryptosporidium infection and diarrhoea in Nepal.
AB  - Three hundred and fifty-four soft, loose or watery stool specimens from patients
      with acute diarrhoea were screened for the presence of Cryptosporidium oocysts. A
      modified Ziehl Neelsen with DMSO staining method was used for detecting
      Cryptosporidium oocysts in the stool samples. The oocysts were identified in 24
      (6.8%) of the samples, while 46 samples (13%) showed mixed infections. Children
      aged between 2 and 10 years were mostly infected by this parasite, while
      infection was more prevalent in females than in males for all the age groups.
      These findings suggest that Cryptosporidium is one of the important aetiologic
      agents of diarrhoea in this population and should be looked for during laboratory
      investigation of diarrhoeal stool samples.

PMID- 8870400
TI  - Hand washing with soap reduces diarrhoea and spread of bacterial pathogens in a
      Bangladesh village.
AB  - Hand washing with soap and water can prevent the spread of diarrhoeal diseases in
      areas where comparatively costly interventions, such as supply of safe water and
      improved sanitation, are not possible. In this study, the practice of hand
      washing with soap and water was instituted in a periurban slum of Dhaka city, and
      the surveillance for diarrhoea sustained for a one-year period. Rates of primary
      and secondary attacks were compared to those of a non-intervention area similar
      in age structure, economic status, education, and other relevant variables.
      Rectal swabs of cases and contacts established aetiologies. There was a large
      (2.6 fold) reduction in diarrhoeal episodes in the intervention area during the
      observation period. Rates of bacterial pathogens were also lower in the
      intervention area. Significant reduction in diarrhoeal incidences was observed in
      all age groups for all pathogens except for rotavirus. These observations if
      implemented as health policy could reduce the spread of diarrhoeal diseases at
      low cost in high risk areas.

PMID- 8870401
TI  - Effect of microwave radiation, pasteurization and lyophilization on the ability
      of human milk to inhibit Escherichia coli adherence to HEp-2 cells.
AB  - The effect of different physical treatments on the ability of colostrum and human
      milk to inhibit the adherence of enteropathogenic Escherichia coli (EPEC) to
      human epithelial cells was studied. Pools of colostrum and milk were submitted to
      microwave radiation, pasteurization or lyophilization, and then tested for the
      ability to inhibit the adherence of EPEC O111:H- to HEp-2 cells. The inhibitory
      effect of untreated colostrum and human milk on localized adherence was not
      significantly modified after exposure to any treatment. The total protein values
      of colostrum and milk were maintained, but IgA concentration and colostral anti
      EPEC IgA were reduced after pasteurization. Nevertheless, the remaining IgA was
      sufficient to be effective in adhesion inhibition assay. Western blotting assays
      carried out with EPEC antigens showed that the treated and untreated pools
      recognize a 94-kDa outer-membrane protein which molecular weight is compatible
      with intimin, an EPEC adhesin related to bacterial attachment to epithelial
      cells. These results suggest that the protection of colostrum and milk to
      infantile diarrhoea due to EPEC remains unalterable after the physical treatments
      studied.

PMID- 8870402
TI  - Production, characterization and immunodiagnostic application of a monoclonal
      antibody to Shiga toxin.
AB  - A mouse monoclonal antibody (MAb ICT7) that is specific for Shiga toxin was
      produced. The MAb neutralises the cytotoxic effects of both purified Shiga toxin
      and culture extracts of Shigella dysenteriae type 1 in HeLa cells. Using MAb ICT7
      and polyclonal rabbit antiserum, a sandwich ELISA was developed. This test
      detects Shiga toxin in both S. dysenteriae type 1 bacterial extracts and in
      stools of patients with S. dysenteriae type 1 infection. The ELISA also detects
      toxin in enterohaemorrhagic Escherichia coli (EHEC) strains positive for Shiga
      like toxin I. The test could detect a minimum of 100 pg of purified Shiga toxin.
      Furthermore, the ELISA did not detect toxin in non-S. dysenteriae type 1 Shigella
      species or Shiga-like toxin II produced by EHEC strains.

PMID- 8870403
TI  - Assay of neutralizing antibodies to animal rotavirus strains and human rotavirus
      serotype G8 by a modified method in the residents of Pune, India.
AB  - In the western literature, four G serotypes (G1-G4) of human rotaviruses have
      been found to be of a major epidemiological importance. During the analysis of
      rotavirus serotypes from faecal samples in Pune, over 50% of specimens could not
      be serotyped with the available monoclonal antibodies against G1-G4 serotypes.
      The results prompted to look for the prevalence of neutralizing antibodies
      against serotypes other than the major human serotypes (G1-G4) in adults.
      Neutralizing antibodies against animal rotavirus serotype, viz. G3, G6 and G10,
      and human rotavirus serotype G8 were determined in adult sera, by a modified
      technique, which is ELISA-based and mechanized. The results showed that, of the
      68 sera tested at 1:100 dilution, 65 (95.58%) were reactive for G3 (SA-11), 52
      (76.47%) for G6 (Bovine Lincoln), 6 (8.82%) for G10 (B223), and 40 (58.82%) for
      G8 (M69) serotypes. It appears that the prevalence of rotaviruses in India may be
      quite different from that in the developed countries.

PMID- 8870404
TI  - Unusual occurrence of cholera in Delhi during January 1994: epidemiological
      investigations.
AB  - Hundreds of laboratory-confirmed cholera cases occur every year in Delhi. However
      from 1965 through 1993, no cases of cholera nor carriers of Vibrio cholerae have
      been detected in the months January and February of all these years.
      Nevertheless, two cases occurred in January 1994. Both were children who acquired
      their infection locally. Six hundred fifty-eight rectal swabs collected from
      possible contacts were negative for V. cholerae. The next isolations could be
      made only in April, which is the usual beginning of the cholera season. The study
      suggests that cholera transmission can occur during the winter months in Delhi,
      but that it is not sustained.

PMID- 8870406
TI  - Factors affecting production of haemolysin by strains of Vibrio fluvialis.
AB  - The in vitro production of haemolysin by Vibrio fluvialis was studied using sheep
      erythrocyte. The effect of the composition of various media and different
      concentrations of sodium chloride on the production of haemolysin and heat
      stability was investigated. Comparatively higher titre of haemolysin production
      was noted in brain heart infusion (BHI) broth. Adding 0.5% NaCl to BHI broth
      reduced the production of haemolysin; adding 5.0% NaCl to the medium totally
      inhibited it. The highest titre of haemolysin was produced at 30 degrees C and 37
      degrees C, whereas no haemolysin was produced at 50 degrees C. Haemolytic
      activity was totally destroyed when heated at 56 degrees C for 30 minutes.
      Haemolysin could be assayed easily following this method.

PMID- 8870405
TI  - Diarrhoea associated with Candida spp.: incidence and seasonal variation.
AB  - To study the incidence and seasonal variation of diarrhoea associated with
      Candida, 978 diarrhoeal stool specimens from patients of all age groups were
      examined by microscopy and culture. Candida spp. was the sole pathogen
      (unassociated with other diarrhoeagenic bacteria, protozoa, or helminths) in
      15.3% of the total cases. Candida albicans (94.9%) was the predominant species
      isolated. The incidence was highest among the infants aged 0-12 months (37.1%),
      followed by a decline in the rest of the children aged less than 5 years with a
      second peak in the people aged over 5 years, including adults. The paediatric age
      group had a significantly higher incidence in the summer season compared to the
      rainy (p < 0.05) or winter (p < 0.01) months. Thus, there was a definite age and
      seasonal variation in the incidence of diarrhoea caused by the overgrowth of
      Candida in the Varanasi region of the Indian subcontinent.

PMID- 8870407
TI  - The use of calcium oxide in controlling house flies in Yangon, Myanmar.

PMID- 8870408
TI  - Fifth annual scientific conference (ASCON V) annual lecture. Health and
      development: lessons from the grassroots.

PMID- 8870409
TI  - How are the social sciences helping empower the poor to promote their own health
      and development?

PMID- 8870410
TI  - Postnatal and postpartal morphology of the mammary gland in nude mice.
AB  - The object of this work was to compare the postnatal and postpartal morphology of
      the mammary gland of nu/nu with that of nu/(+)-mice. All studies were carried out
      on groups of female (athymic) nude mice with NMRI genetic background, their
      nu/(+)-siblings and dams. The various age groups (3, 21, 40, 55, 70 and 120 days)
      each consisted of 6 nu/nu- and 6 heterozygous nu/(+)-mice respectively. The
      morphological examination of the mammary gland tissue were made on histological
      sections and whole mounts. Body weights, total areas of the mammary glands and
      the number of the terminal end buds were compared. The mammary gland of the
      athymic nude mouse exhibited no essential morphological differences from the
      normal developing mammary gland of the hairy euthymic nu/(+)-animal. The area of
      the mammary gland increased with increasing body weight. Both collectives of mice
      differed only in their rate of mammary gland development. As a result, the
      terminal end buds appeared numerously as growth points of mammary gland in nu/(+)
      animals as early as the 21st day of life. The athymic nude mice showed a maximum
      only on the 40th day of life and a lower degree of density and differentiation of
      specific mammary gland structures (lateral buds, lobulo-alveolar glandular
      endings) until the 70th day of life. The mammary gland of 120-day-old animals and
      dams of both animal groups reached the same state of maturity. Thus it is not the
      rate of development of the dam, but other, yet unidentified factors, which
      determine, if successful breeding of nude mice with homozygous parents is
      possible.

PMID- 8870411
TI  - Measurement of salivary cortisol in guinea pigs.
AB  - For collection of saliva, cotton buds (Q-tips) were inserted into the guinea
      pig's cheek pouch, parallel with the cheek teeth. Within 5 minutes, sufficient
      fluid was collected for salivary cortisol measurements. Salivary cortisol was
      about 7 ng/ml after intramuscular (i.m.) injection of 0.2 ml saline. Compared
      with saline treatment, it was drastically increased after i.m. injection of ACTH
      or cortisol. Taking into account the close relationship between the amounts of
      cortisol in saliva and plasma in cortisol- or ACTH-treated animals, we conclude
      that measuring saliva cortisol offers promise as a noninvasive method to monitor
      the changes of adrenocortical function in guinea pigs.

PMID- 8870412
TI  - Cardiopulmonary effects of lying position in anesthetized and mechanically
      ventilated dogs.
AB  - Cardiopulmonary effects of right-lateral and supine (on back) lying position were
      investigated in 8 anesthetized and mechanically ventilated dogs. Complete
      hemodynamic and respiratory monitoring were obtained. Heart rate was
      significantly higher, blood pressure, systemic vascular resistance and left and
      right ventricular stroke work were significantly lower in supine in comparison to
      right-lateral position. Arterial and mixed-venous oxygen tensions and mixed
      venous oxygen saturation were significantly higher in right-lateral position.
      Compliance was significantly higher and peak ventilation pressure significantly
      lower in supine position. Arterio-to-mixed-venous-oxygen content difference,
      oxygen consumption and utilization were significantly higher and respiratory
      quotient was significantly lower in supine position in comparison to right
      lateral position. All other obtained parameters were not be influenced by
      posture.

PMID- 8870413
TI  - Different effect of inhaled nitric oxide on yucatan micropig with and without
      congenital ventricular septal defect.
AB  - A strain of Yucatan micropigs is known to have heritable ventricular septal
      defects (VSDs) and thus may develop overflow pulmonary hypertension. Since
      inhaled nitric oxide (NO) selectively dilates pulmonary vessels, we determined
      its hemodynamic and co-agulatory effects in this new animal model. Eight Yucatan
      micropigs were anesthetized with midazolam, piritramide (a synthetic opioid) and
      vecuronium bromide. The presence and the size of the VSD were determined by using
      transesophageal color flow Doppler echocardiography. Four animals showed VSDs of
      1-2 mm size. Inhaled NO was then administered with increasing inspired
      concentrations of 0, 5, 10, 20, 40, 80 and again 0 ppm NO for 10-min periods. NO
      inhalation did not affect heart rate, right cardiac output, mean arterial
      pressure, pulmonary arterial wedge pressure, or central venous pressure. Inhaled
      NO in animals with proven VSDs decreased pulmonary artery pressure (PAP) in a
      dose dependent manner; 5 ppm NO reduced mean PAP from 25 +/- 2.3 mm Hg to 18 +/-
      0.8 mm Hg (p < 0.05), while pulmonary vascular resistance (PVR) decreased from
      954 +/- 143 dyn.cm. s-5 to 661 +/- 88 dyn.cm.s-5 (p < 0.01) at the same dose. The
      maximum reduction in mean PAP and PVR occurred when 80 ppm NO was inhaled.
      Yucatan micropigs without VSDs did not respond hemodynamically to NO inhalation.
      Methemoglobin levels remained unchanged during the entire study. Platelet
      function was assessed according to the method of BREDDIN and BORN (BORN 1962).
      Initial aggregation and slope were affected when NO inhalation commenced. Yucatan
      micropigs with VSDs may represent a suitable model for further research of the in
      vivo effects of inhaled NO.

PMID- 8870414
TI  - Current status of assisted reproductive technology in Asia and Oceania.
AB  - OBJECTIVE: To summarize the procedures and outcomes of assisted reproductive
      technology (ART) initiated in Asia-Oceanic region in 1992 and 1993. DESIGN: Data
      were collected on an annual summary form and submitted to the Reproductive
      Biology Committee of AOFOG. PARTICIPANTS: Twelve member countries of AOFOG
      submitted data on ART procedures performed in 1992 and 1993-Australia, Egypt,
      Hong Kong, India, Indonesia, Japan, Korea, New Zealand, Pakistan, Singapore,
      Taiwan, and Thailand. Data were collected in 1995 so that the outcomes of all
      pregnancies established would be known. MAIN OUTCOME MEASURES: Clinical
      characteristics of patients, causes of infertility, protocols and outcomes of
      controlled ovarian hyperstimulation (COH), and outcomes of clinical pregnancy
      including abortion, ectopic pregnancy, multiple pregnancy, and congenital
      malformation were measured in each ART procedure. RESULTS: In 1992, 23,872 cycles
      of IVF-ET were performed with 21.8% clinical pregnancy rate (PR) per ET, 4,840
      cycles of GIFT with 29.5% PR per transfer, 1,136 cycles of simultaneous IVF-ET
      and GIFT with 29.9% PR, and 1,563 cycles of ZIFT with 23.1% PR. Total 575
      clinical pregnancies were achieved in cryopreserved ET program, 96 pregnancies in
      oocyte donation program, and 87 pregnancies in microassisted fertilization (MAF)
      program. In 1993, 24,571 cycles of IVF-ET were performed with 21.6% clinical PR
      per ET, 5,240 cycles of GIFT with 28.2% PR per transfer, 1,063 cycles of
      simultaneous IVF-ET and GIFT with 32.0% PR, 1,005 cycles of ZIFT with 21.6% PR,
      5,562 cycles of cryopreserved ET program with 12.8% PR, and 2,198 cycles of MAF
      program with 11.6% PR. Total 117 clinical pregnancies were achieved in oocyte
      donation program. CONCLUSIONS: Although the concepts as well as the status and
      results of ART are continuously changing, this report may be helpful in planning
      the future of ART in Asia-Oceania by analyzing the past history.

PMID- 8870415
TI  - The association of Chlamydia trachomatis/gonococcal infection and tubal factor
      infertility.
AB  - OBJECTIVE: To determine the association of past Chlamydia trachomatis and past
      Neisseria gonorrhoeae infection with tubal factor infertility. METHODS: A cross
      sectional study was conducted. Cases consisted of 55 primary infertile women with
      laparoscopy confirmed tubal damage (group A) and their husbands, consecutively
      attending the Infertility Unit at Maharaj Nakorn Chiang Mai Hospital between 1990
      and 1992; and 58 primary infertile women with laparoscopy confirmed normal tubes
      (group B) and their husbands, consecutively attending the same hospital over the
      same period. Controls consisted of 59 postpartum women (group C) and their
      husbands omitted to the same hospital over the same period as cases. Past
      chlamydial and gonococcal infections were assessed by measuring serum IgG
      antibodies by enzyme immunoassay (EIA). The EIA antigens consisted of purified
      elementary bodies of C. trachomatis serovar L1, or purified alpha pili of N.
      gonorrhoeae strain P9. RESULTS: The prevalence of positive IgG antibody to
      gonococcal pili in sera from group A was 29.1%, significantly higher than the
      prevalence of 5.2% in group B or 3.4% in group C (p = 0.000). The husbands of
      women in group A had a significantly higher prevalence of IgG antibody to
      gonococcal pili (36.4%) than the husbands of women in group B (8.6%) or group C
      (18.6%) (p = 0.002). There was no significant difference in positive IgA antibody
      between case and control groups. After controlling for age, group A showed
      significantly higher prevalences of past gonorrhea (OR = 32.4, 95% CI 4.3, 242.2)
      and past chlamydial infection (OR = 3.2, 95% CI 1.2, 8.5) than group C. The
      husbands of women in group A also had higher prevalences of both types of
      infection than the husbands of women in group C; the odds ratios for past
      gonorrhea or chlamydial infections were 2.8 (95% CI 1.1, 6.9) and 2.9 (95% CI
      1.2, 7.1), respectively. Neither infertile women with normal tubes (group B) nor
      their husbands showed any difference when compared with controls. CONCLUSION:
      These results suggest that in this region of northern Thailand there is an
      association between past gonorrhea and past chlamydial infection and tubal factor
      infertility.

PMID- 8870416
TI  - Serum levels of squamous cell carcinoma antigen and carcinoembryonic antigen as
      tumor markers of vulvar cancer.
AB  - OBJECTIVE: To assess whether squamous cell carcinoma (SCC) antigen and
      carcinoembryonic antigen (CEA) are useful as tumor markers of vulvar cancer.
      METHODS: The serum levels of SCC antigen and CEA were determined for 30 patients
      with invasive vulvar carcinoma. RESULTS: There was a significant difference not
      only between tumor sizes of 2 cm or larger and those of less than 2 cm (p <
      0.001), but also between patients with lymph node metastasis and patients free
      from it (p < 0.001). Tumor marker levels well reflected the response to
      neoadjuvant chemotherapy. The sensitivity to recurrence was 63%, and the
      specificity was 94%. In 2 of 8 recurrent cases, it was only the re-increase in
      tumor markers that indicated the recurrence. CONCLUSION: The measurement of serum
      levels of SCC antigen and CEA is useful not only for preoperative evaluation of
      the risk of lymph node metastasis, but also for the detection of recurrence.

PMID- 8870417
TI  - Immunohistochemical study of c-erb B-2 expression in malignant mixed mullerian
      tumors of the female genital tract.
AB  - OBJECTIVE: To study the expression of c-erb B-2 in gynecologic malignancies,
      especially in malignant mixed mullerian tumors (MMTs). METHODS: Using
      immunohistochemical techniques, we examined 6 cases of primary MMT, 6 cases of
      leiomyosarcoma (LMS), 7 cases of endometrial adenocarcinomas, and 10 cases of
      normal endometria. RESULTS: The expression of c-erb B-2 was observed in the
      carcinomatous area of all 6 cases of MMT (100%), the sarcomatous area of 5 of 6
      cases of MMT (83.3%), in 1 of the 6 cases of LMS (16.7%), in all 7 cases of
      adenocarcinoma (100%), and in all cases of normal epithelial cells (100%), but
      was not observed in any of the cases of normal stromal cells (0%). CONCLUSION:
      The results suggest that the carcinomatous and sarcomatous elements of MMT are
      similar in their expression of c-erb B-2. MMT differed immunohistochemically from
      pure sarcoma cells and normal stromal cells, but resembled pure carcinoma cells
      and normal epithelial cells of the female genital tract.

PMID- 8870418
TI  - The relation between body-fat distribution and lipid metabolism in postmenopausal
      women.
AB  - OBJECTIVE: To evaluate the relationship between body-fat distribution and lipid
      metabolism in postmenopausal women. METHODS: Fifty-four women (mean: 61.8 +/- 7.8
      years old) showing hyperlipidemia and 63 controls were enrolled in this study.
      Their baseline characteristics and body-fat indices, as measured by DEXA, were
      compared. The correlations between the serum-lipid levels and the variables were
      evaluated. RESULTS: The amount of upper-half-body fat and the body-fat ratio were
      significantly higher in the hyperlipidemia group. In single-regression analysis,
      there were low levels of correlation between the serum TC levels and the amount
      of upper-half-body fat and the upper-body fat ratio. There was a low level of
      correlation between the serum TG level and the amount of upper-half-body fat, the
      upper-lower-half-body-fat ratios, and the upper-half-body-fat ratio. After
      adjusting for variables, the serum TC and TG levels best correlated with the
      amount of upper-half-body-fat (r = 0.458, r = 457, respectively). CONCLUSION: In
      postmenopausal women, lipid metabolism is reflected in the amount of upper-half
      body fat, irrespective of age and the body-mass index (BMI).

PMID- 8870419
TI  - Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in women with or without
      gynecologic cancer.
AB  - OBJECTIVE: To detect the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) which is
      an oxygen-radical-forming agent, in the urine of patients with (n = 18) or
      without (n = 10) carcinoma of the female genitalia. None of the patients had been
      receiving any treatment before their urinary 8-OHdG levels were measured.
      METHODS: Urinary 8-OHdG was extracted by a solid-phase technique, and its level
      was determined by high-performance liquid chromatography (HPLC) with an electric
      chemical detector (ECD). RESULTS: We determined that the urinary 8-OHdG level
      decreased with as the age of the patient increased, and was extremely high in
      advanced cancer and recurrent cancer in a considerable number of patients. The
      urinary 8-OHdG level (1,827 +/- 1,500 pmol/kg/day, mean +/- SEM) in 18 patients
      with carcinoma was significantly higher (p < or = 0.05) than that (747 +/- 425
      pmol/kg/day) in 10 patients without carcinoma. CONCLUSION: These results suggest
      that it might be possible to determine the spread of cancer to some extent by
      determining a patient's urinary 8-OHdG level.

PMID- 8870420
TI  - Early asymmetric IUGR and aneuploidy.
AB  - OBJECTIVE: To determine the incidence of chromosomal abnormalities in fetuses
      with asymmetric growth retardation in the second and early third trimesters of
      pregnancy. METHODS: From November 1989 to December 1993, 71 singleton pregnancies
      with asymmetrical growth retardation diagnosed at 15 to 35 weeks gestation had
      detailed ultrasonographic examination for structural malformations and fetal
      karyotyping done. RESULTS: The fetal karyotype was abnormal in 7 (9.9%) of the
      cases. There were 19 growth retarded fetuses with concomitant structural defects.
      The incidence of chromosomal abnormalities in asymmetrical growth retarded
      fetuses with structural defects was 21% (4/19). The incidence of fetal aneuploidy
      in structurally normal fetuses with asymmetrical growth retardation detected
      before 23 weeks gestation was 20% (3/15); while for those presenting between 23
      29 weeks gestation, no abnormal karyotypes were found. CONCLUSION: Although more
      prospective data is needed, our data seems to suggest that fetal karyotyping may
      be unnecessary in structurally normal fetuses with early onset intrauterine
      growth retardation occurring between 23-29 weeks of gestation.

PMID- 8870421
TI  - Plasma exchange in a patient with postpartum HELLP syndrome.
AB  - The case of a patient with HELLP syndrome, who was unresponsive to supportive
      management but successfully treated with plasma exchange, is presented. The
      significance of plasma exchange in the treatment of HELLP syndrome is discussed.

PMID- 8870422
TI  - Prenatal diagnosis of an extensive haemangioma of the fetal leg: a case report.
AB  - Extensive haemangioma with platelet consumption (Kasabach-Merritt syndrome) is
      rare. The lesion is usually a single cutaneous cavernous haemangioma similar to
      that found in our patient. Multiple superficial strawberry naevi were also seen
      all over the rest of the body. This condition was diagnosed antenatally in this
      patient with the use of colour Doppler. There is one recent report where the
      thrombocytopaenia was diagnosed by cordocentesis. Unfortunately the baby
      developed heart failure with intractable coagulopathy and died 2 days later.

PMID- 8870423
TI  - Case report: an exaggerated placental site with a cervical pregnancy.
AB  - An exaggerated placental site (EXPS) is an exuberant nonneoplastic proliferation
      of the intermediate trophoblast at the implantation site. We had a case of an
      EXPS with a cervical pregnancy. We report on this case, including the patient's
      clinical course and immunohistological findings.

PMID- 8870424
TI  - Laparoscopic assisted vecchietti procedure for the creation of a neovagina.
AB  - A case report of a 21-year-old patient with Mayer-von Rokitansky-Kuster-Hauser
      syndrome is presented. A neovagina was created by drawing an olive into the
      vaginal grove and applying continuous tension via sutures passed at laparoscopy
      to a tensioning device on the anterior abdominal wall.

PMID- 8870425
TI  - Outcome of external cephalic version: our experience.
AB  - The aim is to assess the outcome of external cephalic version (ECV) for term
      breech in our clinical setting and the factors involved. Patients with no
      contraindications and who consented to ECV were recruited into this prospective
      study. Terbutalin infusion was used. There were 42 ECV attempts of which 21 (50%)
      were successful. Seventeen of the patients with successful ECV delivered
      vaginally and 4 had cesarean section for various indications. Only 5 of the 21
      unsuccessful ECV delivered vaginally. Thirteen had elective cesarean section and
      2 had emergency cesarean during trial of breech. One patient from the
      unsuccessful ECV group was lost to follow-up. There were 31 (74%) primipara. The
      birth weight of the babies was not a significant factor in the outcome of ECV.
      The type of breech and parity did influence the success rate. External cephalic
      version should be included in the routine management of our breech presentation.

PMID- 8870426
TI  - Choriocarcinoma complicated by splenic rupture: an unusual presentation.
AB  - A patient with choriocarcinoma presenting with acute abdominal pain due to
      splenic rupture from secondary deposits is reported. This rare case exhibited
      several other unusual features including coexisting bilateral ovarian teratomas
      and the absence of any evidence of a primary lesion. Several hemangiomata in the
      liver initially confused the clinic picture.

PMID- 8870427
TI  - A multicentre study to investigate the prevalence of abnormal carbohydrate
      metabolism in Chinese pregnant women.
AB  - OBJECTIVES: To determine the prevalence of abnormal carbohydrate metabolism in
      Chinese pregnant women. To study the inter-relationship between maternal body
      habitus, maternal serum glucose and birth weight of the baby. METHODS:
      Multicentre observational study involving 713 pregnant Chinese women, attending
      antenatal clinics in Beijing, Shanghai, Guangzhou and Hong Kong. RESULTS AND
      CONCLUSION: The overall prevalence of abnormal glucose tolerance was 6.9%. The
      prevalence was 6.8%, 5.5%, 7.2% and 8.1% in Beijing, Shanghai, Guangzhou and Hong
      Kong, respectively. The differences among the centres did not reach statistical
      significance (p = 0.9). The mean ponderal index of women with abnormal glucose
      tolerance was significantly higher than that of women with normal glucose
      tolerance (15.2 vs 14.3, p < 0.01). The birth weight ratio of the babies was
      positively correlated with the maternal height (correlation coefficient 0.23, 95%
      C.I. 0.15-0.30), weight (0.32, 95% C.I. 0.25-0.39) and to a lesser extent, the
      fasting level of serum glucose (0.10, 95% C.I. 0.02-0.28) but not with the 2 hour
      level of serum glucose.

PMID- 8870428
TI  - Hepatitis B virus infection in children: epidemiology, natural course and
      prevention in Taiwan.
AB  - Although most hepatitis B virus (HBV) related chronic liver diseases manifest
      themselves in adulthood, HBV infection usually begins in infancy or early
      childhood in hyperendemic areas. The following factors affect the natural course
      of HBV: 1) host factors: a) initial age of infection: the younger the patient at
      infection, the more chance the disease will run a chronic course. Immune
      tolerance to hepatitis B e antigen (HBeAg) and core antigen persists for a period
      of time in young children. b) the immune status of the host: the usage and
      tapering of immunosuppressants may induce a severe course with a fatal outcome;
      2) maternal carrier status: children of HBeAg seropositive mothers are more
      immune tolerant to HBV, and thus have lower rates of HBeAg and hepatitis B
      surface antigen (HBsAg) seroconversion; and 3) viral factors: mutations of the
      HBV precore, core or core promoter genes are related to fulminant hepatitis B or
      severe chronic hepatitis B. However, this is a matter of contention. Since July
      1984, a nationwide HBV vaccination program has been successfully conducted in
      Taiwan. In 1994, the HBsAg carrier rate in Taipei city was reduced to < 1% in
      children younger than 10 years of age. Continuous efforts in immunoprophylaxis
      will hopefully further reduce the incidence of hepatitis and hepatocellular
      carcinoma in the next generation.

PMID- 8870429
TI  - Invasive Haemophilus influenzae diseases and purulent meningitis in Taiwan.
AB  - We conducted a 3-year Taiwan-wide hospital-based survey of invasive Haemophilus
      influenzae infections in children less than 15 years of age. From January 1992 to
      December 1994, 105 cases (57 boys, 48 girls) were reported. Seventy-three
      patients (69.5%) had meningitis and 32 patients had other diseases (12 pneumonia,
      10 sepsis, 7 cellulitis, 3 arthritis). Fourteen patients (13%) died, all of whom
      had meningitis or sepsis. Among the 63 patients who survived meningitis, 17 (27%)
      had neurologic sequelae and eight (47%) had hearing impairment. The number of
      cases of H. influenzae meningitis (30%) and other H. influenzae diseases (29%)
      peaked in children between 6 and 12 months of age. Patients with invasive
      infections (82%) and meningitis (73%) were younger than 24 months of age. Only 12
      patients (11%) were older than 5 years of age and four had underlying diseases.
      The annual incidence of invasive H. influenzae infections in children less than 5
      years old was 1.9 per 100,000 per year. During the same period a survey of
      purulent meningitis in children younger than 15 years of age was also conducted
      in 20 hospitals. A total of 198 patients, in whom the causative organisms were
      identified, were included; 94 patients were 2 months of age or under and the most
      frequent pathogen was group B streptococci (35 cases, 37%). Among the 104
      patients who were older than 2 months of age, H. influenzae was the leading cause
      (38 cases, 37%). In conclusion, invasive H. influenzae type b (Hib) diseases
      exist in Taiwan but have an incidence lower than in Western countries. Hib
      meningitis is still the most common cause of purulent meningitis in children in
      Taiwan and is an important cause of mortality and morbidity. Continuous active
      surveillance of invasive H. influenzae infections is suggested to determine the
      best time to introduce an Hib conjugate vaccine in Taiwan.

PMID- 8870430
TI  - Cancer patients' knowledge of their diagnoses.
AB  - The most frequently discussed ethical issue on the subject of cancer is whether
      patients should be told their diagnosis. Cancer patients' knowledge of their
      diagnosis and the relationship between patient characteristics and that knowledge
      were evaluated in a cross-sectional study. From July 1992 to December 1993 at Tri
      Service General Hospital, Taipei, a total of 964 patients with cytologically- or
      pathologically-proven cancer were studied. Of those studied, 359 patients (37.2%)
      knew their diagnosis. The proportion of patients who believed that they had a
      benign tumor was 25.1%; 12.6% believed they had nonneoplastic disease
      (inflammation or other chronic disease); 7.5% believed they had precancerous
      changes; and 17.6% knew nothing about their diagnosis. Multivariate analyses
      showed that patients with the following characteristics were inclined to know
      their diagnosis: younger age (20-59 yr), higher levels of education (> 9 yr) with
      relatives of a high socioeconomic status, cancer of a genital organ, cancer
      requiring disfiguring treatment (osteosarcoma, leukemia), cancer in obvious sites
      (head and neck), cancer of more than one type (multiple primary lesions), cancer
      of good prognosis (excluding lung, liver, gall bladder or pancreatic cancers),
      aggressive anticancer treatment and longer duration of pathologic proof (> 14 d).
      The results showed that concealing the diagnosis from cancer patients is still
      very common in Taiwan. Patient's sociodemographic background and disease-related
      factors were the most important patient characteristics related to their
      knowledge of the diagnosis.

PMID- 8870431
TI  - Coamplification of the ZFX and ZFY genes for sex identification in
      preimplantation embryos.
AB  - Knowledge of the sex of an embryo may be particularly useful for couples who have
      a high risk of producing offspring with inherited genetic disorders. We present a
      rapid and reliable nested polymerase chain reaction strategy to simultaneously
      amplify the ZFX and ZFY genes at the single cell level. Forty single blastomeres
      isolated from six triploid preembryos were subjected to coamplification of ZFX
      and ZFY genes. The results obtained from the preembryo were consistent with the
      assigned genotype. The amplification rate was 80% for ZFX and 84% for ZFY. Our
      strategy can be applied to preimplantation diagnosis of single gene disorders,
      and is especially useful for preimplantation diagnosis and prevention of X-linked
      diseases in in vitro fertilization programs.

PMID- 8870432
TI  - How many embryos should be transferred in in vitro fertilization and tubal embryo
      transfer?
AB  - In order to achieve higher pregnancy rates, more than one embryo is usually
      transferred in in vitro fertilization (IVF) programs. Tubal embryo transfer (TET)
      produces an even higher pregnancy rate. However, the number of embryos that
      should be transferred in TET programs remains to be clarified. We studied a
      series of 241 consecutive TET cycles and analyzed their clinical characteristics,
      embryo numbers, cumulative embryo score (CES), and pregnancy outcomes. The
      results demonstrated that 1) four embryos was an adequate number to obtain a
      satisfactory pregnancy rate and fewer multiple pregnancies, 2) older patients and
      cases with male factor had less chance of pregnancy and more than four embryos
      could be transferred, and 3) CES values > 40 were preferred, but for young
      patients with unusually high anxiety about multiple pregnancies, a CES of 21 to
      40 was optimal. A policy of transfer that limits transfer to a maximum of two,
      three or four embryos is not suitable in all cases and other factors (eg,
      repeated IVF failure or older age) should be individually considered. Therefore,
      two equations utilizing CES, age and failure of previous TET as the factors were
      developed to help practitioners to evaluate how many embryos should be
      transferred on an individual basis.

PMID- 8870433
TI  - Galvanotropic and galvanotaxic responses of corneal endothelial cells.
AB  - The effects of weak electric fields (E-fields) on cultured rabbit corneal
      endothelial cells were studied. The cells responded to steady E-fields (2-6 V/cm)
      by elongating their somata 90 degrees to the field (galvanotropism) and by
      migrating (galvanotaxis) towards the anode. During these directional movements,
      pseudopodia and ruffled membranes formed preferentially on the anodal side of the
      cells, while they retracted on the cathodal side. Fluorescent labelling for actin
      showed many stress fibers aligned parallel to the long axes of the elongated
      cells and few aligned toward the anodal direction. Fluorescent labelling for
      vinculin showed the abundance of cell-to-substratum adhesion foci at the termini
      of the stress fibers. Galvanotropic and galvanotaxic cellular movements were
      inhibited by cytochalasin D (0.1-0.5 microgram/mL) and the calmodulin antagonist,
      W-7 (80 mumol/L). These results suggest that E-field induced directional
      movements of corneal endothelial cells constitute a calmodulin-dependent, active
      (not passive) process.

PMID- 8870434
TI  - Outbreak of contact dermatitis related to Acticide EP paste in a paint
      manufacturing factory.
AB  - An outbreak of severe itching, erythematous and edematous dermatitis over the
      extremities and upper back developed in 8 of 17 workers in the raw-materials
      department of a paint manufacturing factory. The outbreak occurred during a 2
      month period when Acticide EP paste (Thor Chemical, Cheshire, UK) was used in
      place of Metatin as a microbiocide (Acima Chemical, Buchs, Switzerland). To
      evaluate the frequency and the etiologic agent of this outbreak, a plant walk
      through, examination and review of photographs of skin lesions followed by
      statistical analysis for association between the development of dermatitis and
      exposure to Acticide paste were performed. Three guinea pigs were subjected to
      patch tests comparing the dermatotoxicity of Acticide EP and Metatin. The results
      showed that 8 out of 17 workers (47%) suffered from contact dermatitis during the
      2-month period. Stratification by occupational exposure further confirmed the
      association between the development of dermatitis and exposure to the Acticide
      paste. The dermatotoxicity test on guinea pigs revealed the marked corrosive
      effect of the paste and the absence of dermatotoxicity of Metatin. After the
      removal of the paste from the raw material, there were no new cases of contact
      dermatitis at the 6 month follow-up. We conclude that Acticide EP paste was the
      responsible offending agent. Because isothiazolinone derivatives are well-known
      antigens and 2-n-octyl-4-isothiazolin-3-one is the active ingredient in Acticide
      EP paste, 2-n-octyl-4-isothiazolin-3-one is the likely cause of the dermatitis.

PMID- 8870435
TI  - Isoniazid-induced fever.
AB  - A rare case of isoniazid (INH)-induced fever is described. A 27-year-old woman
      diagnosed with miliary tuberculosis (TB) began to receive combined anti-TB
      treatment including INH, ethambutol, rifampicin and pyrazinamide on the second
      day of hospitalization. A spiked fever developed in the afternoon of the seventh
      hospital day. There was no evidence of a hypersensitivity reaction. All
      examinations including liver function tests, routine biochemistry tests, serum
      titer of antinuclear antibody and rheumatoid factor were within normal limits.
      The blood leukocyte count was also within normal range and no evidence of
      infection at other sites was found. Following the discontinuance of anti-TB
      agents, the patient's body temperature gradually returned to normal. When the
      patient was rechallenged with INH, the high fever recurred. The fever subsided
      again after the discontinuance of INH, and her recovery followed a smooth course
      thereafter, on combination therapy with rifampicin, ethambutol and pyrazinamide.
      This experience demonstrates the potential of INH to cause an isolated fever
      without other manifestations, which may be misdiagnosed as an infectious process.
      Though it is very rare, INH-induced fever must be considered when fever develops
      during anti-TB treatment.

PMID- 8870436
TI  - Laparoscopic splenectomy: preliminary experience.
AB  - The role of conventional open splenectomy in the treatment of idiopathic
      thrombocytopenic purpura (ITP) is well known. As improvement in laparoscopic
      instruments and techniques have been made, laparoscopic surgery has been
      significantly extended to include more general surgical procedures. From July
      1993 to March 1995, five patients with refractory ITP were treated by
      laparoscopic splenectomy at National Taiwan University Hospital. The entire
      procedure was completed under laparoscopic guidance in which four ports were used
      in four of the five cases. The operative time for these four patients ranged from
      180 to 330 minutes with an average time of 225 minutes. The estimated blood loss
      ranged from 100 to 400 mL with an average of 175 mL. No intraoperative blood
      transfusions were required. A Penrose drain was in place for 2 to 3 days. All of
      the patients were able to tolerate a regular diet within 1 postoperative day. The
      average postoperative hospital stay was 5.25 days. No complications occurred. The
      remaining laparoscopic surgery was unsuccessful, requiring conversion due to
      severe bleeding. In conclusion, laparoscopic splenectomy is a feasible and safe
      procedure for patients with ITP. It may be an alternative choice for a variety of
      hematologic and pathologic conditions involving the spleen.

PMID- 8870437
TI  - Reproducibility of the first-phase insulin release in the intravenous glucose
      tolerance test.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a slowly progressive autoimmune
      disease. In the prediabetic phase of IDDM, the intravenous glucose tolerance test
      (IVGTT) demonstrates a progressive decline in the first-phase insulin response.
      The first-phase insulin response to intravenous glucose may enable individuals at
      risk of IDDM to be identified and preventive therapy to be instituted. However,
      the reproducibility of the first-phase insulin response is controversial. The aim
      of this study was to determine the variability of the first-phase insulin
      response to intravenous glucose. Ten healthy normal volunteers underwent two
      IVGTT within a 1 week interval, using the Islet Cell Antibody Register User's
      Study (ICARUS)-recommended standard protocol. The first-phase insulin response to
      intravenous glucose was expressed as the sum of the 1- and 3-minute insulin
      concentrations (muU/mL) and the total 0 to 10 minute insulin area under the curve
      (muU.min.mL-1). Variability was represented by the coefficient of variation (CV).
      The within-subject median CV was 21.2% for the sum of the 1- and 3-minute insulin
      concentrations and 23.9% for the total 0 to 10 minute insulin area under the
      curve. In conclusion, the reproducibility of the first-phase insulin response to
      intravenous glucose is poor. Hence, caution should be exercised when the IVGTT is
      applied to prediabetic IDDM patients for longitudinal study.

PMID- 8870438
TI  - Infantile hypertrophic pyloric stenosis after surgery for esophageal atresia with
      tracheoesophageal fistula.
AB  - Infants with esophageal atresia and tracheoesophageal fistula may have other
      associated anomalies. The development of infantile hypertrophic pyloric stenosis
      in the postoperative course of esophageal atresia with tracheoesophageal fistula
      is rarely reported. Because its symptoms may mimick postoperative complications
      such as gastroesophageal reflux or anastomotic stricture, the diagnosis may be
      delayed. We report an infant who had surgery for esophageal atresia with
      tracheoesophageal fistula at birth. The infant presented with nonbilious
      projectile vomiting at 4 weeks of age. Plain abdominal x-ray, barium upper
      gastrointestinal series and abdominal ultrasonography all supported the diagnosis
      of hypertrophic pyloric stenosis. The diagnosis was confirmed during surgery.
      After pyloromyotomy, the patient's condition improved.

PMID- 8870439
TI  - Perforated Meckel's diverticulum in a neonate.
AB  - A case of Meckel's diverticulum is reported in an eight-day-old male baby, the
      youngest patient to have had this condition at National Taiwan University
      Hospital. The baby had been affected by bilious vomiting of 3 days' duration and
      abdominal distension before being brought to the hospital. A perforated Meckel's
      diverticulum was found during emergency laparotomy. The resected Meckel's
      diverticulum did not contain ectopic tissue. The narrow lumen and narrow base of
      the diverticulum was thought to be the cause of poor self-emptying and subsequent
      acute inflammation and perforation.

PMID- 8870440
TI  - Successful multidisciplinary treatment of an endodermal sinus tumor of the pineal
      region.
AB  - The case presented is a 17-year-old male patient with a pineal region endodermal
      sinus tumor manifested by obstructive hydrocephalus and upward gaze limitation.
      The highly aggressive nature of this rare malignancy was evidenced by spontaneous
      tumor bleeding. The patient was treated with a cerebrospinal fluid (CSF) shunt
      and microsurgical tumor excision followed by irradiation and combination
      chemotherapy consisting of cisplatin, vincristine, methotrexate and bleomycin.
      The response to therapy was monitored by serial measurements of serum and CSF
      alpha-fetoprotein level. The patient remains free of any clinical or radiographic
      evidence of tumor recurrence 38 months after the initial diagnosis. This
      experience supports the rationale for an aggressive multidisciplinary approach
      toward this rare and highly malignant neoplasm.

PMID- 8870441
TI  - Treating benign prostatic hyperplasia with finasteride in Chinese men: one-year
      experience.
AB  - To evaluate the long-term efficacy and safety of finasteride in the treatment of
      symptomatic benign prostatic hyperplasia (BPH), 50 patients with symptomatic BPH
      were initially evaluated in a double blind, placebo-controlled study for 6
      months. The patients were then treated with finasteride in an open extension
      study in which all received the same dose of finasteride (5 mg/day) for another 6
      months. Among the patients (n = 23) who completed the extension study, prostate
      volume was significantly reduced from baseline by 15%, maximum urine flow rate
      improved by 1.9 mL/second, symptom scores improved by 37% and serum prostatic
      specific antigen (PSA) level decreased by 1.34 ng/mL. Other than serum PSA level,
      these data differed insignificantly from data at the end of the first 6 months.
      The adverse events observed at the end of the first 6 months (two patients with
      decreased sexual libido and two with impotency) persisted throughout the study
      extension period. At the end of the 12 months study, one more patient reported
      decreased libido. The sustained clinical efficacy and low incidence of side
      effects of daily treatment with finasteride 5 mg for 1 year indicate that
      finasteride is safe and effective for managing symptomatic BPH in Chinese men.

PMID- 8870442
TI  - Teenage pregnancy: a dead-end trap.

PMID- 8870443
TI  - Children's plight in Georgia: dark.

PMID- 8870444
TI  - Can doctors help keep kids in school?

PMID- 8870445
TI  - MAG and the Alliance: helping children make healthy choices.

PMID- 8870446
TI  - Strategies to reduce low birthweight babies in Georgia.
AB  - Despite traditional interventions to control for potential socioeconomic and
      behavioral mediators, the relationship between black race and ethnicity and LBW
      persists. Some researchers have questioned whether the criterion for LBW should
      be different for blacks and whites.

PMID- 8870447
TI  - Child abuse: past, present, future.

PMID- 8870448
TI  - The partnership between behavioral and preventive medicine.
AB  - We must look at the "big picture" when encouraging positive change in people's
      lives. Simplistic fads and magical techniques rarely promote lasting change. A
      more holistic approach that incorporates the psychologic and behavioral
      components is much more powerful. We need to adopt a model of change that
      promotes an overall positive lifestyle and an idea of wellness that is not
      focused on absence of disease. Physicians should stress that psychosocial aspects
      be considered, discussed, and addressed to enhance true positive lifestyle
      changes that focus on personal responsibility as the most effective locus of
      control. Positive cultural and family beliefs, religious and social norms, self
      care and self responsibility are the fundamental building blocks in our later
      efforts to promote health education and healthy lifestyles. To be most cost
      effective, these efforts need to be incorporated into the curricula of young
      children.

PMID- 8870449
TI  - A sign of hope: promising solutions in response to youth violence.

PMID- 8870450
TI  - An analysis of knowledge of sexually transmitted disease among Georgia high
      school seniors.

PMID- 8870451
TI  - Malignant hyperthermia in a 3-month-old infant: a case report.
AB  - First described in 1960, malignant hyperthermia (MH) is a relatively rare
      disorder of muscle metabolism triggered by specific anesthetic agents and
      presenting as a rapidly evolving intraoperative crisis. The syndrome is more
      prevalent among children (1/15,000 exposures to anesthesia) than adults (1/50,000
      exposures), but has not been thought to occur in children younger than 1 year of
      age. This is a case report of a 3-month-old, 4.85 kg white male infant who
      developed MH while undergoing repair of a right inguinal hernia. The case is
      unique not only with respect to the age of the patient but also with the
      extremely elevated creatine phosphokinase (CPK) 13 hours postoperatively.

PMID- 8870452
TI  - Our past is their future: the making and selling of "MD Health Plan".

PMID- 8870453
TI  - Changes in Medicaid.

PMID- 8870454
TI  - Managed health care ideology--capitalism or communism?

PMID- 8870455
TI  - Sam--an effortless mentor.

PMID- 8870456
TI  - Understanding and complying with the Georgia Health Records Act.
AB  - Most physicians are generally aware of the fact that, in some cases, under some
      circumstances, physicians are required to provide some patients with copies of
      some medical records. Surprisingly, however, most physicians are not aware of the
      fact that, since 1984, Georgia has had a statute on the books which imposes some
      fairly specific requirements on physicians and other healthcare providers, in
      terms of providing copies of medical records to patients. In this month's Legal
      Section, we take a closer look at the Georgia Health Records Act; we also
      describe the results of the first appellate-level case interpreting the
      provisions of that Act, recently decided by the Georgia Court of Appeals.

PMID- 8870457
TI  - JCAHO/Orion.

PMID- 8870458
TI  - Patient satisfaction is the real bottom line.

PMID- 8870459
TI  - Ode to the mosquito.

PMID- 8870460
TI  - The mark of a scientist.

PMID- 8870461
TI  - The Brown University School of Medicine Class of 1996.

PMID- 8870462
TI  - MD2000: a competency-based curriculum for the Brown University School of
      Medicine.

PMID- 8870463
TI  - The people's health competency collegium.

PMID- 8870464
TI  - The scientific basis of medicine.

PMID- 8870465
TI  - A panoply of patient encounters: the close encounter collegium.

PMID- 8870466
TI  - Doctor-patient relationships: know thy patient, know thyself.

PMID- 8870467
TI  - Lyme disease in Rhode Island: three years of surveillance.

PMID- 8870468
TI  - Vitamin D3- induced histological changes in the corpuscles of stannius of a
      freshwater catfish, Heteropneustes fossilis kept either in artificial freshwater,
      calcium-rich freshwater or calcium-deficient freshwater.
AB  - Vitamin D3 (50 I.U./100 g body wt) was injected daily intraperitoneally to the
      fish H. fossilis maintained in artificial freshwater, calcium-rich freshwater and
      calcium deficient freshwater. The animals were killed on day 1, 3, 5, and 10. The
      serum calcium levels were estimated and CS were fixed for histological studies.
      Administration of vitamin D3 induced hypercalcemia in the fish kept in all the
      three different media. The AF-positive cells of CS of vitamin D3 treated
      specimens kept in artificial freshwater, calcium-rich freshwater and calcium
      deficient freshwater depict hyperactivity which is expressed by their
      degranulation and increased nuclear volume. The AF-negative cells of CS of
      vitamin D3-treated fish kept in artificial freshwater have not shown any change,
      however, the AF-negative cells of the fish treated with vitamin D3 and maintained
      in calcium-rich freshwater and calcium-deficient freshwater exhibit a decrease in
      their nuclear volume.

PMID- 8870469
TI  - Basal Fos immunoreactivity in myenteric neurons of guinea pig.
AB  - The enteric nervous system (ENS) is capable of mediating intestinal reflexes in
      the absence of connections to the CNS. Nuclear immunoreactivity for Fos, a
      protein encoded by the c-fos proto-oncogene, has previously been used to
      visualize activated cells. We have attempted to use a commercial antibody to Fos
      to investigate the proportion of activated neurons in the myenteric ganglia of
      guinea pigs. Neuronal nuclei which demonstrated Fos Immunoreactivity (F-IR) were
      counted in preparations fixed immediately after removal from the animals.
      Demonstration of all myenteric neurons in adjacent segments by staining with
      cuprolinic blue revealed that neurons with F-IR comprised a subset (65-75%) of
      all neurons. These results have led us to conclude that ENS has a basal activity
      for intestinal functions and this could be demonstrated easily by Fos
      immunoreactivity.

PMID- 8870470
TI  - Structural characteristics of the superior venae cavae wall at the
      intrapericardium segment in adults and aging individuals.
AB  - The authors admit that the conjunctive-muscular constitution of the walls of the
      superior venae cavae throughout the length of the intrapericardium segment and
      the debouchement in the right atrium, associated with the presence of a
      myocardium sheath can be made up of a functional device of sphincter form able to
      act on the control of the blood flow to the interior of the arterial chamber as
      well as stopping blood flow during the arterial systole. The fixation of the
      venous wall to the deep chamber of the serous pericardium, contributes to growth
      in resistance during the elevation of venous pressure, making possible the
      preservation of integrity of the superior venae cavae. The expansion of fasciculi
      of nodal fibers in the right wall of the superior venae cavae permits that the
      unlocked impulse in the S-A node also reaches the vascular wall contributing to
      the shortening and diminuation in caliber of the vein.

PMID- 8870471
TI  - The uncinate bulla.
AB  - In this study a total of 175 coronal CT scans of the nasal cavity and paranasal
      sinuses have been investigated. The uncinate bulla was detected in 21 (11 male
      and 10 female) cases of 175 patients. Out of 21, 17 were bilateral while 4 were
      unilateral. The incidence of the uncinate bulla was found as 12%.

PMID- 8870472
TI  - The anatomy of lamina pretrachealis fasciae cervicalis.
AB  - The definitions concerning the fascia pretrachealis is either contradictory or
      insufficient in anatomy textbooks. The fascia pretracheatis is clinically
      important in the procedure of tracheostomy, mediastinascopy and also in tracheal
      and bronchial trauma. The anatomy of the fascia pretrachealis (extension,
      relation and the attachments) was reexamined using cadaveric preparations and the
      clinical value of the fascia is reinforced. The fascia pretrachealis is attached
      to the upper brim and to the oblique line of the thyroid cartilage and continued
      its course on the anterior surface of the trachea and fused with the advantitia
      of arch of the aorta, posterior aspect of pulmonary artery and the pericardium.
      Laterally it is attached to the cartilagenous part of the trachea. Also
      contraversial literature concerning description of the fascia pretrachealis has
      been evaluated.

PMID- 8870473
TI  - Intermediate cells detected in electron microscopic observation of the rat spiral
      ganglion.
AB  - Morphological features of the rat spiral ganglion cells were investigated in
      serial sections by electron microscopy. Materials were obtained from healthy rat
      temporal bones after perfusion with glutaraldehyde. Cochleas were removed and
      prepared by routine electron microscopic methods. EDTA was used for
      decalcification. When semithin sections were studied two distinct types of the
      neurons were observed, the large and the small cell bodies, which were mostly
      myelinated. The differences between the organelles of these two cell type were
      analyzed under electron microscope. The large cell bodies were rich in
      cytoplasmic organelles and intracytoplasmic microfilaments were sparse. The small
      neurons contained fewer cytoplasmic organelles and were rich in microfilaments.
      In addition to the known types of neurons, higher magnifications indicated 1-2%
      of all these cells were intermediate cells. The morphological structure was
      basically the same as that of the large neurons but they were rich in cytoplasmic
      organelles including the microfilaments.

PMID- 8870474
TI  - ATP induces large channel endocytosis with concomitant increase in cell density.
AB  - Large channel endocytosis is considered to be the characteristic of specialized
      endocytic cells like macrophages and phagocytes while small pit endocytosis
      involving clathrin protein coatings are the membrane recycling macromolecular
      pathways for most eukaryotic cells. We show here that extracellular ATP induced
      cells to internalize their plasma membrane by large channel endocytosis. In the
      process of plasma membrane internalization, flat protracted cells round up and
      become easily detachable from the substrate. Scanning transmission ion microscopy
      (STIM) revealed an increase in cell density as the ATP treated cells assumed a
      rounded morphology. The increase in cell density could be attributed to endocytic
      internalization of cell membrane and debris.

PMID- 8870475
TI  - Stereological study of the sexual dimorphism in mouse submandibular glands.
AB  - The sexual dimorphism of the mouse submandibular glands was studied by
      stereological methods. Albino mice of both sexes aged 140 days were used. Their
      average weight was 34.7 g por males and 26.0 g for females. The following
      morphometric dimensions were evaluated for the acini, intercalated ducts,
      convoluted granular tubules, striated ducts, excretory ducts and stroma: volume
      density, total volume, surface density, total external surface, surface-to-volume
      ratio, nuclear and cellular volume, and absolute number of cells. We also
      determined the mean diameters and estimated the total length of striated ducts
      and granular tubules in the gland. Analysis of the results showed that sexual
      dimorphism is present in all the morphological compartments of the mouse
      submandibular glands.

PMID- 8870476
TI  - A study of the nutrient foramina in the shaft of the fibula.
AB  - In this study a total of 305 adult fibulae were examined to determine the number
      and location of the nutrient foramina in the shafts of bones. Of 305 fibulae, 281
      had one foramen, 12 had two and the remaining 12 had no foramen. The foramina
      were seen primarily on the posterior surface (48.36%) and in the middle third
      (98.00%) of the bone. The mean foraminal index of the fibula was found to be
      48.14 +/- 0.46.

PMID- 8870477
TI  - Effect of zinc on the epithelial lining of mice epididymis--a light microscopic
      study.
AB  - Intraperitoneal zinc chloride was administered at 7.5 micrograms/g body weight
      and 15 micrograms/g body weight to 10-12 weeks old Swiss albino mice for 5
      consecutive days. Control animals were given normal saline. The testis and
      epididymis were dissected and examined under the light microscope. Micrographs of
      the testes appeared normal in both treated and nontreated animals. However the
      group of animals treated with the higher dosage of zinc chloride showed evidence
      of rupture and collapse of the epididymal epithelial lining. The testes were not
      affected probably because of (a) known higher testicular concentration of
      metallothioneins which can bind the zinc and consequently detoxify the metal and
      (b) "stratified" epithelium comprising of spermatogenic and Sertoli cells.

PMID- 8870478
TI  - A morphological study on the V2 segment of the vertebral artery.
AB  - Morphometric investigations on the V2 segment of the vertebral artery, showed
      that, it did not have a constant calibre during its course within the foramina
      transversaria. The vertebral artery, entering the foramina transversaria reduced
      its calibre and further continued to reduce until C3 level, above C3 it began to
      reincrease its calibre and at C1 level reached its largest calibre. Measurements
      on the muscular thickness, showed an increase as ascending through the foramina
      transversaria. The widening and narrowing of the vertebral artery within the
      foramina transversaria was attributed as tortious artery or congenital anomaly.
      This study showed that it was the normal anatomy of the artery within the
      foramina transversaria.

PMID- 8870479
TI  - The accessory tendon of the extensor indicis muscle.
AB  - The extensor indicis and the extensor pollicis longus muscles differentiates from
      the extensor digitorum profundus muscle. The extensor indicis muscle is an
      unstable muscle concerning its variations. Kosugi (1989) found the frequency of
      variations of this muscle to be 20% and described 18 different types of
      variations of this muscle. This study describes a rare case of the extensor
      indicis muscle. The extensor indicis muscle develops an accessory tendon in
      between the extensor indicis and extensor pollicis longus muscle. It passes under
      the extensor retinaculum. At the level of 2nd metacarpal bone, the accessory
      extensor indicis tendon is connected to the tendon of the extensor pollicis
      longus muscle by a intertendinous connection.

PMID- 8870480
TI  - A new method of artificial bone modeling for medical education.
AB  - We have developed an artificial bone modeling method by using negative cast
      technique. As we decided to use this material in medical student training, we
      insisted on producing a long-standing and not expensive material therefore we
      chose a polyester resin.

PMID- 8870481
TI  - A case report; trilobular spleen?
AB  - During dissection course a spleen with a pyramidal extremity was noted.
      Literature reviewed and this rare case has been presented.

PMID- 8870482
TI  - The measurements of some anthropometric landmarks of the mandible; a preliminary
      anatomical study.
AB  - In this study, the morphometric measurements were done on human cadaver mandibles
      including ramus height and width, angle between ramus and corpus, the relation
      between foramen mentale and teeth. The aim of this study was to establish some
      standards with the achieved results in order to expand these studies in some
      reconstructive surgical areas. As a result, the standard measurements were
      established under the heads of short and long ramus, acute and obtuse angle
      mandibles.

PMID- 8870483
TI  - The importance of the angulation and termination of external jugular vein in
      central venous catheterization in newborn.
AB  - The purpose of this study is to evaluate the termination and angulation of the
      EJV (External jugular vein) and the number and the position of its valves so as
      to improve our understanding of the anatomy of the EJV and to make the
      manuplation easier in central venous catheterization in newborn. The present
      study was carried out on 50 newborn cadavers (31 male, 19 female). 100
      Dissections were bilaterally made. The angle of the termination of the EJV was
      measured. Its termination angle was also radiologically measured. Its termination
      was classified into three types: In 72 cases (72%), EJV flowed into the jugulo
      subclavian venous confluence; in 26 cases (26%), into the SCV (Subclavian vein)
      at a distance (1cm) from its junction with the IJV (Internal jugular vein); in 2
      cases (%2) into the trunk of the IJV. Its termination types were asymmetrical in
      12 cadavers (24%) and symmetrical in 38 (76%). Its termination angle was found
      both anatomically or radiologically to be within 25 degrees-60 degrees. The
      valves of the EJV were examined in 10 newborn cadavers. They were most often bi
      valvular, in paraostial position and were of a membranous character. It is
      important to remind the physician about the surprises related to its terminations
      and angulations during the central venous catheterization.

PMID- 8870484
TI  - Med school revisited: 1941 to '44-and so on to 1996 and beyond.

PMID- 8870485
TI  - Students: fulfilling the dream.

PMID- 8870487
TI  - Patient information on the internet.

PMID- 8870486
TI  - Postoperative delay.

PMID- 8870488
TI  - Nutritional status and mortality in respiratory failure caused by tuberculosis.
AB  - A retrospective analysis of the records of all patients admitted to the intensive
      care unit with respiratory failure and nonmiliary tuberculosis was conducted to
      determine variables that might be predictive of survival. Nutritional status, as
      reflected by the patient's serum albumin and hemoglobin, were the best predictors
      of survival and were more helpful than the widely accepted APACHE II scoring
      system. This observation suggests that early and aggressive attention to
      improving the patient's nutritional status may be as important as effective
      antitubercular therapy and mechanical ventilation in salvaging these individuals.

PMID- 8870489
TI  - Traumatic pseudocyst of the spleen.

PMID- 8870490
TI  - Medical revolution: the prevention and treatment of stroke, 1996. Part 1. Stroke
      prevention and carotid endarterectomy.

PMID- 8870491
TI  - Shortness of breath and chest pain in a patient with scleroderma.

PMID- 8870492
TI  - Preventing traumatic brain injury.

PMID- 8870493
TI  - Loss prevention.

PMID- 8870494
TI  - RNA polymerase II transcription control.

PMID- 8870495
TI  - The role of general initiation factors in transcription by RNA polymerase II.
AB  - Transcription initiation on protein-encoding genes represents a major control
      point for gene expression in eukaryotes, and is mediated by RNA polymerase II and
      a surprisingly complex array of general initiation factors (TFIIA, -B, -D, -E, -F
      and -H) that are highly conserved from yeast to man. Elucidation of structural
      and functional features of these factors on model promoters has revealed insights
      into biochemical mechanisms and provides a basis for understanding their
      regulation on diverse promoters by gene- and cell-specific activators.

PMID- 8870496
TI  - Mediator of transcriptional regulation.
AB  - A multi-protein complex, termed mediator, has been isolated from yeast, based on
      its requirement for transcriptional activation in a system reconstituted from
      pure RNA polymerase II and general transcription factors. Mediator polypeptides
      include the products of many genes previously recovered from screens for
      mutations affecting transcription. This connection between biochemical and
      genetic studies reveals that mediator is important for both activation and
      repression of transcription, and that mediator plays a role in transcriptional
      regulation in vivo as well as in vitro. Mediator binds the carboxy-terminal
      domain of RNA polymerase II, forming a polymerase holoenzyme, whose possible
      association with additional proteins is a subject of some controversy.

PMID- 8870497
TI  - TAFs mediate transcriptional activation and promoter selectivity.
AB  - The TATA-binding protein (TBP)-associated factors (TAFs) of TFIID play a central
      role in RNA polymerase II transcriptional regulation. Some TAFs can function as
      co-activators that mediate the activation signal from enhancer-bound regulators.
      In addition, interactions between selected TAFs and core elements direct promoter
      selectivity by RNA polymerase II.

PMID- 8870498
TI  - The human general co-factors.
AB  - The human general co-factors were discovered during biochemical fractionation of
      mammalian nuclear extracts in functional in vitro assays. They appear to act in
      concert with other co-activators that bind tightly to the TATA-binding protein
      and RNA polymerase II. Several co-factors have been shown to interact with
      general transcription factors, leading either to activation or repression of
      transcription. At least one subgroup of co-factors that enhance the effects of
      activators on transcription are DNA-binding proteins located in the chromatin. In
      fact, one co-factor, the repressor NC2, is structurally related to histones. The
      understanding of the molecular interplay of such components of the initiation
      complex in the chromatin-including general co-factors, other co-factors, general
      factors and activators-will be a major challenge in the future.

PMID- 8870499
TI  - The multiple roles of transcription/repair factor TFIIH.
AB  - TFIIH is by far the most complex of the basal RNA polymerase II transcription
      factors. It is a protein kinase, a bi-directional DNA helicase and is essential
      for both transcription and nucleotide excision repair (NER). Furthermore, the
      factor can activate cyclin-dependent kinases and so might play a role in cell
      cycle regulation. The recent elucidation of the subunit composition of TFIIH has
      shown an extraordinary conservation of its structure from yeast to human.

PMID- 8870501
TI  - Tuberculosis. The WHO/IUATLD Global Project on Antituberculosis Drug-Resistance
      Surveillance.

PMID- 8870500
TI  - The RNA polymerase II general elongation factors.
AB  - Synthesis of eukaryotic messenger RNA by RNA polymerase II is governed by the
      concerted action of a set of general transcription factors that control the
      activity of polymerase during both the initiation and elongation stages of
      transcription. To date, five general elongation factors [P-TEFb, SII, TFIIF,
      Elongin (SIII) and ELL] have been defined biochemically. Here, we discuss these
      transcription factors and their roles in controlling the activity of the RNA
      polymerase II elongation complex.

PMID- 8870502
TI  - Compliance with mammography screening guidelines: 1995 Mammography Attitudes and
      Usage Study Report.

PMID- 8870503
TI  - Impact of National Cancer Institute revised mammography screening guidelines on
      women 40-49.

PMID- 8870504
TI  - Women's health centers and managed care.

PMID- 8870505
TI  - Births to unmarried mothers: trends and obstetric outcomes.

PMID- 8870506
TI  - Identification and treatment of exercise resistance: a syndrome associated with
      eating disorders.

PMID- 8870507
TI  - Preventive health practices and perceived health status among women over 50.

PMID- 8870508
TI  - End-of-life decision making: understanding the goals of care. ACOG Committee on
      Ethics.

PMID- 8870510
TI  - Understanding the goals of care in end-of-life decision making: a committee
      opinion at the bedside.

PMID- 8870509
TI  - Women's health and end-of-life decision making.

PMID- 8870511
TI  - Preventive ethics and end-of-life decisions.

PMID- 8870512
TI  - Cooperation yields best results for improved reproductive health care.

PMID- 8870513
TI  - Mental models and temporal reasoning.
AB  - We report five experiments investigating reasoning based on temporal relations,
      such as: "John takes a shower before he drinks coffee". How individuals make
      temporal inferences has not been studied hitherto, but we conjectured that they
      construct mental models of events, and we developed a computer program that
      reasons in this way. As the program shows, a problem of the form: a before b b
      before c d while b e while c What is the relation between d and e? where a, b, c,
      etc. refer to everyday events, calls for just one model, whereas a problem in
      which the second premise is modified to c before b calls for multiple models
      because a may occur before c, after c, or at the same time as c. Experiments 1-3
      showed that problems requiring one mental model elicited more correct responses
      than problems requiring multiple models, which in turn elicited more correct
      answers than multiple model problems with no valid answers. Experiment 4
      contrasted the predictions of the model theory with those based on formal rules
      of inference; its results corroborated the model theory. Experiment 5 confirmed
      that a premise leading to multiple models took longer to read than the
      corresponding premise in one-model problems, and that latency to respond
      correctly was greater for multiple-model problems than for one-model problems. We
      conclude that the experiments corroborate the mental model theory.

PMID- 8870514
TI  - What do children know about the universal quantifiers all and each?
AB  - Children's comprehension of the universal quantifiers all and each was explored
      in a series of experiments using a picture selection task. The first experiment
      examined children's ability to restrict a quantifier to the noun phrase it
      modifies. The second and third experiments examined children's ability to
      associate collective, distributive, and exhaustive representations with sentences
      containing universal quantifiers. The collective representation corresponds to
      the "group" meaning (for All the flowers are in a vase all of the flowers are in
      the same vase). The distributive representation implies a pairing (e.g., each
      flower paired with a vase for Each flower is in a vase). The exhaustive
      representation exhausts both sets (e.g., for The flowers are in the vases all the
      flowers are in vases and all the vases have flowers in them). Four- to 10-year
      olds children had little difficulty restricting the quantifier all to the noun it
      modified in a task which required them to attend to the group feature of all. In
      contrast, only 9- and 10-year-olds were able to solve the task when the
      quantifier was each and the pictures showed entities in partial one-to-one
      correspondence. Children showed a preference for associating collective pictures
      with sentences containing all and distributive pictures with sentences containing
      each. The results suggest that between the ages of 5 and 10 years, children's
      semantic representations undergo less radical changes than others have proposed.
      Instead, developmental change may occur gradually as children acquire linguistic
      cues which map onto existing semantic representations.

PMID- 8870515
TI  - On the equivalence of superordinate concepts.
AB  - Psychological studies of superordinates have generally treated them as
      equivalent. However, many languages distinguish mass superordinates (e.g.,
      clothing) from count superordinates (e.g., vehicle). In the present paper,
      experimental evidence is presented which suggests that the two types of
      superordinates are conceptually distinct as well. One study showed that the
      members of mass superordinates more often co-occur. A second study showed that
      people more often interact with the members of mass superordinates in temporal
      proximity whereas people primarily interact with single members of count
      superordinates on a specific occasion. Also, properties that characterize an
      individual are a more salient aspect of count superordinates. These findings
      imply that mass superordinates refer to unindividuated groups of objects, united
      by spatial and functional contiguity. Two other studies supported this hypothesis
      by showing that the class inclusion relation between a single object and a
      category is stronger for count superordinates. Taken together, the findings
      suggest that mass superordinates are not true taxonomic categories. We relate the
      findings to previous views of superordinates and to the count/mass distinction in
      general.

PMID- 8870516
TI  - Authenticity in learning: multimedia design projects in the social studies for
      students with disabilities.
AB  - Proponents of educational reform highlight the importance of creating
      instructional environments that encourage students' active involvement in the
      learning process. To be so involved, students with and without disabilities must
      construct knowledge, evaluate the products of their work, and engage in the
      design of solutions to authentic problems. We believe that these goals are
      especially important for students with disabilities, many of whom are passive
      learners who experience difficulty with the flexible use of knowledge and skills.
      Our analysis of the research evidence leads us to conclude that students'
      thinking skills and attitudes are enhanced when they collaborate in the solution
      of authentic problems. We view the social skills curriculum as a rich source of
      authentic problems that affords opportunities to promote thinking by enabling
      argument about controversial issues. Further, we contend that educational
      multimedia are potentially powerful tools for constructing knowledge, especially
      when used in collaborative project-based instructional environments, or
      multimedia design projects. We review evidence about the efficacy of multimedia
      design projects in promoting students' construction of knowledge, thinking, and
      problem solving, and discuss some potential challenges to the efficacy of this
      approach.

PMID- 8870517
TI  - Computer-based study strategies for students with learning disabilities:
      individual differences associated with adoption level.
AB  - This article reports results from a study of the use of technology to support
      students with learning disabilities in the use of effective study strategies.
      Thirty secondary students were given laptop computers and taught a variety of
      computer-based study strategies designed to facilitate information recording,
      organization, and manipulation. Results suggest that students adopted this
      innovation at three levels: (a) Power Users (skilled, independent users,
      integrating the computer into their schoolwork); (b) Prompted Users (skilled
      computer users, but requiring prompting); and (c) Reluctant Users (having limited
      knowledge and working only under supervision). Intelligence and reading test
      scores were associated with adoption levels in a statistically significant way.

PMID- 8870518
TI  - Assistive technology for postsecondary students with learning disabilities.
AB  - An increasing number of students with learning disabilities are attending
      postsecondary institutions. To meet the educational demands of these students,
      support service providers will likely rely on assistive technology. This article
      lists types of assistive technology appropriate for use with persons with
      learning disabilities at the postsecondary level and discusses ways in which
      assistive technology enhances learning. Additionally, an overview of legislation
      that has had an impact on assistive technology at the postsecondary level is
      presented. Issues involving assistive technology programs at the postsecondary
      level are discussed. Postsecondary assistive technology program components,
      device selection, and training guidelines also are outlined.

PMID- 8870519
TI  - Multimedia: enhancing instruction for students with learning disabilities.
AB  - This article includes an introduction to the terminology and different types of
      formats of current multimedia technologies. Integration opportunities and
      challenges for using multimedia for students with learning disabilities are
      discussed in the framework of learning environments. Multimedia used as a
      demonstration station, learning research station, and creation station offers
      teachers and students possibilities for enhancing the teaching-learning
      environment.

PMID- 8870520
TI  - A federal perspective on special education technology.
AB  - This article examines more than a decade of changes in special education research
      and in the use of technology. It discusses evolving research and projects funded
      by the Office of Special Education Programs (OSEP) and raises questions about the
      use of specific methodologies and about whether children with disabilities are
      being prepared for the world in which they will live. And, finally, it describes
      OSEP's Technology, Educational Media, and Materials strategic program agenda that
      will drive future planning and priorities.

PMID- 8870521
TI  - Traumatic brain injury: 1990s update--introduction to the special series.

PMID- 8870522
TI  - Brain imaging and behavioral outcome in traumatic brain injury.
AB  - Brain imaging studies have become an essential diagnostic assessment procedure in
      evaluating the effects of traumatic brain injury (TBI). Such imaging studies
      provide a wealth of information about structural and functional deficits
      following TBI. But how pathologic changes identified by brain imaging methods
      relate to neurobehavioral outcome is not as well known. Thus, the focus of this
      article is on brain imaging findings and outcome following TBI. The article
      starts with an overview of current research dealing with the cellular pathology
      associated with TBI. Understanding the cellular elements of pathology permits
      extrapolation to what is observed with brain imaging. Next, this article reviews
      the relationship of brain imaging findings to underlying pathology and how that
      pathology relates to neurobehavioral outcome. The brain imaging techniques of
      magnetic resonance imaging, computerized tomography, and single photon emission
      computed tomography are reviewed. Various image analysis procedures, and how such
      findings relate to neuropsychological testing, are discussed. The importance of
      brain imaging in evaluating neurobehavioral deficits following brain injury is
      stressed.

PMID- 8870523
TI  - Assessing children with traumatic brain injury during rehabilitation: promoting
      school and community reentry.
AB  - Children with traumatic brain injuries (TBI) require a comprehensive,
      multidisciplinary evaluation during rehabilitation to promote recovery and to
      facilitate a smooth transition to home and school. This article summarizes the
      common consequences of TBI and reviews a process-oriented approach to assessing
      children with moderate to severe TBI during rehabilitation. An emphasis is placed
      on early and regular communication among rehabilitation specialists, family
      members, and educators. Such collaboration permits clear identification of
      functional abilities and increases the child's potential for a positive long-term
      outcome.

PMID- 8870524
TI  - Children and adolescents with traumatic brain injury: reintegration challenges in
      educational settings.
AB  - Changes in federal law have paved the way for students with traumatic brain
      injury (TBI) to receive special educational services. Although not all students
      with TBI need special education, many will need careful planning for
      reintegration into the classroom. The present article presents information about
      the range of services that need to be considered for these students and the
      problems that can affect students' academic and social functioning.
      Characteristics that distinguish this group of students from peers with special
      learning needs are highlighted and specific suggestions are made to help
      educators work more effectively with these students when they return to school. A
      case study is used to highlight the issues discussed.

PMID- 8870525
TI  - Validity of the Auditory Continuous Performance Test in differentiating central
      processing auditory disorders with and without ADHD.
AB  - The use of continuous performance tasks has been examined as a potential measure
      for clinical/laboratory identification of Attention-deficit/hyperactivity
      disorder. The present study compared the performance of 30 children, 26 boys and
      4 girls ranging in age from 9-0 to 12-11, with central auditory processing
      disorders (CAPD) who did not meet criteria for coexisting ADHD with the
      performance of children with CAPD coexisting with ADHD (CAPD/ADHD) on the
      Auditory Continuous Performance Test (ACPT). In interpreting the results, the
      variability as well as the actual counts for correct responses and total errors
      were considered. Results indicated limited potential for the use of the ACPT in
      the differential diagnosis of ADHD. Implications of the results as well as
      considerations for future research are discussed.

PMID- 8870526
TI  - Form-specific visual priming for new associations in the right cerebral
      hemisphere.
AB  - In three experiments, we examined the internal processing mechanisms of
      relatively independent visual-form subsystems. Participants first viewed
      centrally presented word pairs and then completed word stems presented beneath
      context words in the left or right visual field. Letter-case-specific priming in
      stem completion was found only when the context word was the same word that had
      previously appeared above the primed completion word and the items were presented
      directly to the right cerebral hemisphere. This pattern of results was not found
      when participants deliberately recollected previously presented words when
      completing the stems. Results suggest that holistic processing, not parts-based
      processing as assumed in many contemporary theories of visual-form recognition,
      is performed in a subsystem that distinguishes specific instances in the same
      abstract category of form and that operates more effectively in the right
      hemisphere than in the left hemisphere.

PMID- 8870527
TI  - The perception of number from the separability of the stimulus: the Stroop effect
      revisited.
AB  - The literature on numerical perception is reviewed from the standpoint of
      research on selective attention, and predictions are made concerning the
      dimensional interaction between physical and numerical size of numerals. We
      manipulated stimulus differences to make the classification of numerical value
      slightly better (Experiment 1), substantially better (Experiment 2), or worse
      (Experiments 3-4) than classification of physical size. Garner, Stroop, and
      redundancy effects were used to gauge the degree of interactive processing. For
      nearly matched discriminability, both number and size appeared separable when the
      dimensions were varied orthogonally, but showed Stroop interference and
      redundancy gain when the dimensions were varied in a correlative fashion. When
      mismatched, asymmetric Garner and Stroop effects emerged in orthogonal contexts
      along with Stroop and redundancy gains in correlative contexts. These findings
      define a unique relation: Numerical value and physical size were optionally
      separable dimensions. We conclude that a magnitude representation is not
      mandatory for the perception of numerals. Our conclusions offer a new perspective
      for understanding both numerical perception and the Stroop phenomenon itself.

PMID- 8870528
TI  - Vowel mutability and lexical selection in English: evidence from a word
      reconstruction task.
AB  - This study introduces a new paradigm for investigating lexical processing. First,
      an analysis of data from a series of word-spotting experiments is presented
      suggesting that listeners treat vowels as more mutable than consonants in
      auditory word recognition in English. In order to assess this hypothesis, a word
      reconstruction task was devised in which listeners were required to turn word
      like nonwords into words by adapting the identity of either one vowel or one
      consonant. Listeners modified vowel identity more readily than consonant
      identity. Furthermore, incorrect responses more often involved a vowel change
      than a consonant change. These findings are compatible with the proposal that
      English listeners are equipped to deal with vowel variability by assuming that
      vowel identity is comparatively underdefined. The results are discussed in the
      light of theoretical accounts of speech processing.

PMID- 8870529
TI  - Picture-word differences in a sentence verification task.
AB  - Effects of picture-word format were investigated with four problem-solving items.
      In Experiment 1, picture-word input was presented for 8 sec followed by a test
      sentence that included verbatim and inference statements. Subjects made a
      true/false reaction time to the test sentence. In Experiment 2, the input
      remained on the screen while the test sentence was presented with varied stimulus
      onset asynchronies from 0 to 1,000 msec. Results showed that responses to
      pictures were faster than responses to words, and the format effect was larger
      with inference than with verbatim sentences. The picture advantage seemed to be
      due to the nature of the input and how information is extracted from it. The
      findings are discussed within the context of text-processing theories (Glenberg &
      Langston, 1992; Larkin & Simon, 1987).

PMID- 8870530
TI  - Category typicality effects in episodic memory: testing models of
      distinctiveness.
AB  - Category typicality effects were investigated within the context of three models
      of distinctiveness: a univariate model, a fixed-multifeature model, and a
      weighted-multifeature model. High-typical, medium-typical, and atypical targets
      were embedded in lists containing a background set of medium- to high-typicality
      items. Atypical items were more poorly recalled than were medium- and high
      typical items independently of list structure. In recognition, subjects who
      studied high-typical items had difficulty discriminating between high-typical
      items that were and were not presented as part of the list. However, item
      typicality had little effect on the recognition performance of subjects who did
      not study high-typical items. These findings were consistent with the weighted
      multifeature model of distinctiveness.

PMID- 8870531
TI  - Isolated and interrelated concepts.
AB  - A continuum between purely isolated and purely interrelated concepts is
      described. Along this continuum, a concept is interrelated to the extent that it
      is influenced by other concepts. Methods for manipulating and identifying a
      concept's degree of interrelatedness are introduced. Relatively isolated concepts
      can be empirically identified by a relatively large use of nondiagnostic
      features, and by better categorization performance for a concept's prototype than
      for a caricature of the concept. Relatively interrelated concepts can be
      identified by minimal use of nondiagnostic features, and by better categorization
      performance for a caricature than for a prototype. A concept is likely to be
      relatively isolated when subjects are instructed to create images for their
      concepts rather than find discriminating features, when concepts are given
      unrelated labels, and when the categories that are displayed alternate rarely
      between trials. The entire set of manipulations and measurements supports a
      graded distinction between isolated and interrelated concepts. The distinction is
      applied to current models of category learning, and a connectionist framework for
      interpreting the empirical results is presented.

PMID- 8870532
TI  - Remote analogical reminding.
AB  - Remote analogical reminding is hypothesized to occur when one episode is cued by
      another sharing similar themes but not similar object, character, or event
      descriptions. We report three experiments exploring this view. Subjects'
      remindings in Experiment 1 showed sensitivity to remote analogical similarity
      even though targets were encoded only briefly in an incidental learning paradigm.
      Experiment 2 subjects showed reliable remindings of remote analogs with study
      test delays of up to 1 week. Experiment 3 demonstrated that remote analogical
      reminding effects are not an artifact of subjects' editing nonanalogical
      remindings. All experiments supported the hypothesis that human memory is
      sensitive to remote analogical similarity. We discuss the implications of these
      findings for memory models. Future progress requires the development of formal
      models that quantify factors relevant to reminding performance, such as reminding
      interference, transfer-appropriate processing, and domain expertise.

PMID- 8870533
TI  - On people's understanding of the diagnostic implications of probabilistic data.
AB  - Two lines of prior research into the conditions under which people seek
      information are examined in light of two statistical definitions of
      diagnosticity. Five experiments are reported. In two, subjects selected
      information in order to test a hypothesis. In the remaining three, they selected
      information in order to convince someone else of the truth of a known hypothesis.
      A total of 567 university students served as subjects. The two primary
      conclusions were as follows: (1) When the task is highly structured by the
      environment, subjects select information diagnostically, and (2) when the task is
      less structured, so that subjects must seek relevant information not manifest,
      they select information pseudodiagnostically. Possible relations to other
      laboratory inference tasks and to clinical judgment are discussed.

PMID- 8870534
TI  - When to trust the data: further investigations of system error in a scientific
      reasoning task.
AB  - When evaluating experimental evidence, how do people deal with the possibility
      that some of the feedback is erroneous? The potential for error means that
      evidence evaluation must include decisions about when to "trust the data." In
      this paper we present two studies that focus on subjects' responses to erroneous
      feedback in a hypothesis testing situation-a variant of Wason's (1960) 2-4-6 rule
      discovery task in which some feedback was subject to system error: "hits" were
      reported as "misses" and vice versa. Our results show that, in contrast to
      previous research, people are equally adept at identifying false negatives and
      false positives; further, successful subjects were less likely to use a positive
      test strategy (Klayman & Ha, 1987) than were unsuccessful subjects. Finally,
      although others have found that generating possible hypotheses prior to
      experimentation increases success and task efficiency, such a manipulation did
      little to mitigate the effects of system error.

PMID- 8870535
TI  - How examples may (and may not) constrain creativity.
AB  - Three experiments were performed to test Smith, Ward, and Schumacher's (1993)
      conformity hypothesis-that people's ideas will conform to examples they are shown
      in a creative generation task. Conformity was observed in all three experiments;
      participants tended to incorporate critical features of experimenter-provided
      examples. However, examination of total output, elaborateness of design, and the
      noncritical features did not confirm that the conformity effect constrained
      creative output in any of the three experiments. Increasing the number of
      examples increased the conformity effect (Experiment 1). Examples that covaried
      features that are naturally uncorrelated in the real world led to a greater
      subjective rating of creativity (Experiment 2). A delay between presentation and
      test increased conformity (Experiment 3), just as models of inadvertent
      plagiarism would predict. The explanatory power of theoretical accounts such as
      activation, retrieval blocking, structured imagination, and category abstraction
      are evaluated.

PMID- 8870536
TI  - Outcome assessment of psychotherapy.

PMID- 8870537
TI  - Psychotherapy practice and research. Repairing a strained alliance.
AB  - Although the gap between psychotherapy practice and research has been present for
      some time, recent pressures for accountability from outside the system-managed
      health care and biological psychiatry-necessitate that we take steps to close
      this gap. One such step has been for psychotherapy researchers to specify a list
      of empirically validated therapies. However, as researchers who also have a
      strong allegiance to clinical practice, we are concerned that the conceptual and
      methodological constraints associated with outcome research may become clinical
      constraints for the practicing therapist. We firmly believe that, more than ever
      before, the time is ripe for us to develop a new outcome research paradigm that
      involves an active collaboration between researcher and practicing clinician.

PMID- 8870538
TI  - The tripartite model and the Consumer Reports study.
AB  - This article relates the Consumer Reports (1995) study to the framework of the
      tripartite model of mental health and therapeutic outcomes (H. H. Strupp & S. W.
      Hadley, 1977) and calls attention to major unsolved problems in the assessment of
      therapeutic change. The model envisions three perspectives for evaluating
      outcomes: adaptive behavior (society), sense of well-being, and personality
      structure. The self-report perspective is viewed as having its own validity;
      however, it needs to be complemented by the other two perspectives of the model.
      Integration of the three perspectives has remained a somewhat elusive goal.

PMID- 8870539
TI  - The efficacy and effectiveness of psychotherapy relative to medications.
AB  - A recent survey by Consumer Reports (1994) found that people who received
      psychotherapy were generally pleased with their experience and that their
      satisfaction was unrelated to the type of treatment or the addition of
      medications. M.E.P. Seligman (1995) argued that these findings demonstrate the
      value of psychotherapy and suggested that such survey methodologies may be
      superior to randomized clinical trials in this regard because they study what
      occurs in actual clinical practice. Although such approaches provide important
      information, they are no substitute for controlled clinical trials when it comes
      to drawing causal inferences. However, the study does highlight the importance of
      defining outcome in the broadest possible fashion and of addressing the external
      validity of the findings obtained. Attention to such considerations has
      implications for the relative value of drugs and psychotherapy.

PMID- 8870540
TI  - Studying the effectiveness of psychotherapy. How well can clinical trials do the
      job?
AB  - Although there has been much discussion of the recent Consumer Reports (CR) study
      (1995) on the effectiveness of psychotherapy, there is little new information
      reported either in the CR article or in M. E. P. Seligman's (1995) discussion of
      the findings. The findings that are new are hard to interpret because of serious
      methodological problems. In fact, the CR study is similar in many ways to H. J.
      Eysenck's (1952) controversial report on the effectiveness of psychotherapy, a
      study that has been rejected by the field despite the fact that it avoided some
      of the methodological shortcomings of the CR study. It would be a mistake to put
      forth a design rejected in the 1950s as an exemplar of good effectiveness
      research, especially when better alternatives exist. Clinical trials, despite
      many limitations, can answer all of the questions regarding the effectiveness of
      psychotherapy posed by M. E. P. Seligman, without the interpretive ambiguities
      and other methodological problems inherent in surveys such as the one published
      in CR.

PMID- 8870541
TI  - Health care policy, psychotherapy research, and the future of psychotherapy.
AB  - In a quest for accountability in the delivery of health services, health care
      policymakers in both government and private sectors are creating clinical
      practice guidelines, many of which heavily emphasize medical and pharmacological
      approaches. Yet, there are now sufficient data to support the efficacy of
      psychotherapeutic procedures for a wide variety of specific disorders, and it
      seems now is the appropriate time to communicate these findings to health care
      policymakers and the public at large. At the same time, data must be developed on
      the delivery of these interventions by frontline clinicians in the settings where
      they practice. The emergence of practice research networks may accomplish this
      latter goal.

PMID- 8870542
TI  - Evaluation of psychotherapy. Efficacy, effectiveness, and patient progress.
AB  - Treatment-focused research is concerned with the establishment of the comparative
      efficacy and effectiveness of clinical interventions, aggregated over groups of
      patients. The authors introduce and illustrate a new paradigm-patient-focused
      research-that is concerned with the monitoring of an individual's progress over
      the course of treatment and the feedback of this information to the practitioner,
      supervisor, or case manager.

PMID- 8870543
TI  - Calibration of measures for psychotherapy outcome studies.
AB  - Many findings in psychology, including those in psychotherapy, lack
      interpretability because measures are not in any meaningful metric. Measures need
      to be calibrated so as to endow them with inherent meaning. In particular, it is
      important to calibrate measures against behaviors and real events in people's
      lives. Approaches to calibrating measures include calibration against direct
      personal experience, against cross-experiential equivalents, and against cross
      modal equivalents, to reflect empirically established behavioral implications as
      well as just noticeable differences in behavior or between people. Psychological
      measures may never be as closely calibrated as those for physical properties, but
      wider reporting of unstandardized regression equations would be of great help.
      Psychological measures also need to be calibrated against each other so as to
      permit easy transformations of values or substitutions of measures. Finally,
      greater standardization of measures is recommended so as to produce better bases
      for calibration.

PMID- 8870544
TI  - Science as an ally of practice.
AB  - Well-founded criticisms of the Consumer Reports (CR; 1995) study of psychotherapy
      include possible bias of the CR sample; limitations of self-report; and the
      limitations of cross-sectional, retrospective data. Poorly founded criticisms
      concern "consumer satisfaction" and the claim that the remarkably good effects of
      long-term therapy resulted from spontaneous remission, that psychotherapy effects
      were small, and that nondoctoral providers did as well as doctoral-level
      providers. Both the experimental method (efficacy) and the observational method
      with causal modeling (effectiveness) answer complementary questions, and they
      both do so by eliminating alternative possible causes. Efficacy studies, however,
      cannot test long-term psychotherapy because long-term manuals cannot be written
      and patients cannot be randomized into two-year-long placebo controls, so the
      "empirical validation" of long-term therapy will likely come from effectiveness
      studies. Such studies of long-term therapy, of qualifications of providers, and
      of clinical judgment versus case management are urgently needed as practice
      confronts managed care.

PMID- 8870545
TI  - Finance ... the nation's 100 leading integrated delivery systems reported
      combined gross revenues of $82 billion for the last fiscal year.

PMID- 8870546
TI  - Policy ... hey, big spender.

PMID- 8870547
TI  - Physicians ... more U.S. doctors are moving into medical groups.

PMID- 8870548
TI  - Consumers ... the public's not in the know.

PMID- 8870549
TI  - Speed demon. Does the Pacificare/FHP merger signal a new race for market
      dominance?

PMID- 8870550
TI  - Balancing acts: emergency departments' search for a safety net.
AB  - Crushing chest pain that won't go away? Go to the emergency department. Need a
      pregnancy test? Go to the emergency department. Anything in between? Don't worry
      the emergency department will take care of it. As one patient puts it, "If you're
      willing to wait, they're willing to see you." Well, no more. Budgets are being
      slashed, and there are fewer doctors and nurses to help. What to do? Try "triage
      out," the latest trend to whisk patients through the emergency department doors.

PMID- 8870551
TI  - Chronic care. A cure for emergencies that aren't.

PMID- 8870552
TI  - Community health. A link in the food chain.

PMID- 8870553
TI  - Integrated systems. Not ready for prime time.

PMID- 8870554
TI  - Academic medicine. Med school on the make.

PMID- 8870556
TI  - Hepatitis B and admission to medical school.

PMID- 8870555
TI  - Prescribing antidepressants in general practice.

PMID- 8870557
TI  - Chronic fatigue syndrome.

PMID- 8870558
TI  - Quality of care through the patient's eyes.

PMID- 8870559
TI  - Diagnosing Creutzfeldt-Jakob disease.

PMID- 8870561
TI  - Tobacco firms face no-win, no-fee action.

PMID- 8870560
TI  - Doctor aids first legal euthanasia act.

PMID- 8870563
TI  - Whose sperm is it anyway?

PMID- 8870565
TI  - End to insurers using genetic data urged.

PMID- 8870566
TI  - Myths dispelled about chronic fatigue syndrome.

PMID- 8870567
TI  - South African health reform on the rails.

PMID- 8870568
TI  - Can different patient satisfaction survey methods yield consistent results?
      Comparison of three surveys.
AB  - OBJECTIVE: To examine the consistency of survey estimates of patient satisfaction
      with interpersonal aspects of hospital experience. DESIGN: Interview and postal
      surveys, evidence from three independent population surveys being compared.
      SETTING: Scotland and Lothian. SUBJECTS: Randomly selected members of the general
      adult population who had received hospital care in the past 12 months. MAIN
      OUTCOME MEASURES: Percentages of respondents dissatisfied with aspects of patient
      care. RESULTS: For items covering respect for privacy, treatment with dignity,
      sensitivity to feelings, treatment as an individual, and clear explanation of
      care there was good agreement among the surveys despite differences in wording.
      But for items to do with being encouraged and given time to ask questions and
      being listened to by doctors there was substantial disagreement. CONCLUSIONS:
      Evidence regarding levels of patient dissatisfaction from national or local
      surveys should be calibrated against evidence from other surveys to improve
      reliability. Some important aspects of patient satisfaction seem to have been
      reliably estimated by surveys of all Scottish NHS users commissioned by the
      management executive, but certain questions may have underestimated the extent of
      dissatisfaction, possibly as a result of choice of wording.

PMID- 8870569
TI  - Value of thallium-201 imaging in detecting adverse cardiac events after
      myocardial infarction and thrombolysis: a follow up of 100 consecutive patients.
AB  - OBJECTIVE: To determine the prognostic role of thallium-201 imaging compared with
      that of exercise electrocardiography in patients with acute myocardial infarction
      treated by thrombolysis. DESIGN: Patients who remained free of adverse cardiac
      events six weeks after myocardial infarction had stress and rest 201TI imaging
      and exercise electrocardiography and were followed up for 8-32 months. Adverse
      cardiac events (death, reinfarction, unstable angina, and congestive heart
      failure) were documented. SETTING: Large district general hospital, Middlesex.
      SUBJECTS: 100 consecutive male and female patients who were stable six weeks
      after thrombolysis for myocardial infarction. MAIN OUTCOME MEASURES: Prediction
      of occurrence of adverse cardiac events after myocardial infarction by exercise
      cardiography and 201TI myocardial perfusion imaging. RESULTS: Reversible
      ischaemia on 201TI imaging predicted adverse cardiac events in 33 out of 37
      patients with such events during follow up (hazard ratio 8.1 (95% confidence
      interval 2.7 to 23.8), P < 0.001). Exercise electrocardiography showed reversible
      ischaemia in 33 patients, of whom 13 had subsequent events, and failed to predict
      events in 24 patients (hazard ratio 1.1 (0.56 to 2.2), P = 0.8). CONCLUSION:
      201TI imaging is a sensitive predictor of subsequent adverse cardiac events in
      patients who have received thrombolysis after acute myocardial infarction,
      whereas exercise electrocardiography fails to predict outcome.

PMID- 8870571
TI  - Sex differences in case fatality before and after admission to hospital after
      acute cardiac events: analysis of community based coronary heart disease
      register.
AB  - OBJECTIVE: To determine whether the reported higher case fatality in hospital
      after an acute cardiac event in women can be explained by sex differences in
      mortality before admission and in baseline risk factors. DESIGN: Analyses of data
      from a community based coronary heart disease register. SETTING: Auckland region,
      New Zealand. SUBJECTS: 5106 patients aged 25-64 years with an acute cardiac event
      leading to coronary death or definite myocardial infarction within 28 days of
      onset, occurring between 1986 and 1992. MAIN OUTCOME MEASURES: Case fatality
      before admission, 28 day case fatality for patients in hospital, and total case
      fatality after an acute cardiac event. RESULTS: Despite a more unfavourable risk
      profile women tended to have lower case fatality before admission than men (crude
      odds ratio 0.88; 95% confidence interval 0.77 to 1.02). Adjustment for age,
      living arrangements, smoking, medical history, and treatment increased the effect
      of sex (0.72; 0.60 to 0.86). After admission to hospital, women had a higher case
      fatality than men (1.76; 1.43 to 2.17), but after adjustment for confounders this
      was reduced to 1.18 (0.89 to 1.58). Total case fatality 28 days after an acute
      cardiac event showed no significant difference between men and women (0.85; 0.70
      to 1.02) CONCLUSIONS: The higher case fatality after an acute cardiac event in
      women admitted to hospital is largely explained by differences in living status,
      history, and medical treatment and is balanced by a lower case fatality before
      admission.

PMID- 8870572
TI  - What information is available on request from drug advertisers in India?

PMID- 8870570
TI  - Differences in mortality and morbidity in African Caribbean and European people
      with non-insulin dependent diabetes mellitus: results of 20 year follow up of a
      London cohort of a multinational study.
AB  - OBJECTIVE: To examine differences in morbidity and mortality due to non-insulin
      dependent diabetes in African Caribbeans and Europeans. DESIGN: Cohort study of
      patients with non-insulin dependent diabetes drawn from diabetes clinics in
      London. Baseline investigations were performed in 1975-7; follow up continued
      until 1995. PATIENTS: 150 Europeans and 77 African Caribbeans with non-insulin
      dependent diabetes. MAIN OUTCOME MEASURES: All cause and cardiovascular
      mortality; prevalence of microvascular and macrovascular complications. RESULTS:
      Duration of diabetes was shorter in African Caribbeans, particularly women.
      African Caribbeans were more likely than the Europeans to have been given a
      diagnosis after the onset of symptoms and less likely to be taking insulin. Mean
      cholesterol concentration was lower in African Caribbeans, but blood pressure and
      body mass index were not different in the two ethnic groups. Prevalence of
      microvascular and macrovascular complications was insignificantly lower in
      African Caribbens than in Europeans. 59 Europeans and 16 African Caribbeans had
      died by the end of follow up. The risk ratio for all cause mortality was 0.41
      (95% confidence interval 0.23 to 0.73) (P = 0.002) for African Caribbeans v
      Europeans. This was attenuated to 0.59 (0.32 to 1.10) (P = 0.1) after adjustment
      for sex, smoking, proteinuria, and body mass index. Further adjustment for
      systolic blood pressure, cholesterol concentration, age, duration of diabetes,
      and treatment made little difference to the risk ratio. Unadjusted risk ratio for
      cardiovascular and ischaemic heart disease were 0.33 (0.15 to 0.70) (P = 0.004)
      and 0.37 (0.16 to 0.85) (P = 0.02) respectively. CONCLUSIONS: African Caribbeans
      with non-insulin dependent diabetes maintain a low risk of heart disease.
      Management priorities for diabetes developed in one ethnic group may not
      necessarily be applicable to other groups.

PMID- 8870573
TI  - Hepatitis B and admission to medical school: an audit of British medical school
      policy.

PMID- 8870574
TI  - Lay people's attitudes to treatment of depression: results of opinion poll for
      Defeat Depression Campaign just before its launch.
AB  - OBJECTIVE: To investigate the attitudes of the general public towards depression
      before the Defeat Depression Campaign of the Royal Colleges of Psychiatrists and
      General Practitioners; these results form the baseline to assess the change in
      attitudes brought about by the campaign. DESIGN: Group discussions generated data
      for initial qualitative research. The quantitative survey comprised a doorstep
      survey of 2003 people in 143 places around the United Kingdom. RESULTS: The lay
      public in general seemed to be sympathetic to those with depression but reluctant
      to consult. Most (1704 (85%)) believed counselling to be effective but were
      against antidepressants. Many subjects (1563 (78%)) regarded antidepressants as
      addictive. CONCLUSIONS: Although people are sympathetic towards those with
      depression, they may project their prejudices about depression on to the medical
      profession. Doctors have an important role in educating the public about
      depression and the rationale for antidepressant treatment. In particular,
      patients should know that dependence is not a problem with antidepressants.

PMID- 8870575
TI  - Antidepressant drug use in primary care: a record linkage study in Tayside,
      Scotland.

PMID- 8870576
TI  - Cross sectional database analysis of antidepressant prescribing in general
      practice in the United Kingdom, 1993-5.

PMID- 8870577
TI  - Interaction 3: How to examine heterogeneity.

PMID- 8870578
TI  - Cluster analysis and disease mapping--why, when, and how? A step by step guide.
AB  - Growing public awareness of environmental hazards has led to an increased demand
      for public health authorities to investigate geographical clustering of diseases.
      Although such cluster analysis is nearly always ineffective in identifying causes
      of disease, it often has to be used to address public concern about environmental
      hazards. Interpreting the resulting data is not straightforward, however, and
      this paper presents a guide for the non-specialist. The pitfalls include the fact
      that cluster analyses are usually done post hoc, and not as a result of a prior
      hypothesis. This is particularly true for investigations prompted by reported
      clusters, which have the inherent danger of overestimating the disease rate
      through "boundary shrinkage" of the population from which the cases are assumed
      to have arisen. In disease surveillance the problem of making multiple
      comparisons can be overcome by testing for clustering and autocorrelation. When
      rates of disease are illustrated in disease maps undue focus on areas where
      random fluctuation is greatest can be minimised by smoothing techniques. Despite
      the fact that cluster analyses rarely prove fruitful in identifying causation,
      they may-like single case reports-have the potential to generate new knowledge.

PMID- 8870579
TI  - Doctor in the lab: what is it like for a doctor to work with scientists?
AB  - As clinical academic medical departments strive to improve the quality of their
      research, clinicians and scientists are forced into closer liaison. In many
      cases, clinical departments now have research laboratories directed by "basic
      scientists" but often staffed, in part at least, by doctors. To someone who has
      not worked in one, these laboratories may seem uncompromising and forbidding work
      environments. This article presents a "case report" written from the viewpoints
      of the doctor, the scientist, and the professor.

PMID- 8870580
TI  - Community care and social services.
AB  - The aim of community care is to enable people with various types of disability to
      live in their own homes, rather than in institutions. This involves the provision
      of support and services at home by various agencies. After a critical report in
      1986 identified problems with coordination and flexibility of community care
      services, the white paper Caring for People (1989) stated the government's aim to
      provide a "needs led," responsive range of services, promoting maximum
      independence of those wishing to live at home rather than enter institutional
      care. New arrangements were introduced in 1993, involving a formal assessment
      procedure and the production of a personalized care plan for each individual,
      incorporating services provided by private and voluntary agencies as well as by
      social services departments. This article describes the components of community
      care services supplied by local social services authorities, including housing
      adaptations, equipment, telephones and alarms, home care, meals, and respite
      care.

PMID- 8870581
TI  - Adrenal mass with virilisation: importance of endocrine investigation.

PMID- 8870582
TI  - ABC of work related disorders. Absence from work.

PMID- 8870583
TI  - Certification of cause of death in patients dying soon after proximal femoral
      fracture. All such deaths must be reported to the coroner.

PMID- 8870584
TI  - Certification of cause of death in patients dying soon after proximal femoral
      fracture. Mortality inferred from death certificates reflects coroners' practice,
      not the true mortality.

PMID- 8870585
TI  - Certification of cause of death in patients dying soon after proximal femoral
      fracture. Postmortem examination should always be carried out for deaths due to
      trauma.

PMID- 8870586
TI  - ABC series may be anachronistic in era of evidence based medicine.

PMID- 8870587
TI  - Contraceptive implants. High resolution ultrasonography facilitates removal.

PMID- 8870588
TI  - Contraceptive implants. Complete, understandable information is essential.

PMID- 8870589
TI  - Contraceptive implants. Use is declining and may peak again around 1999.

PMID- 8870590
TI  - Pharmaceutical representatives. Guidelines exist on making effective use of time
      spent with representatives.

PMID- 8870592
TI  - Regulating complementary medicine. Researchers into complementary therapy do not
      have to "sacrifice their therapeutic integrity".

PMID- 8870593
TI  - Regulating complementary medicine. Statutory regulation is essential.

PMID- 8870594
TI  - Regulating complementary medicine. Only 0.08% of funding for research in NHS goes
      to complementary medicine.

PMID- 8870596
TI  - Fundholding practice's draft policy on ethical use of resources. Policy is
      inconsistent.

PMID- 8870597
TI  - Fundholding practice's draft policy on ethical use of resources. Policy is
      mechanism by which decisions might be reached.

PMID- 8870598
TI  - Advertisements in the BMJ. Advertisements for drugs used in disorders with a
      negative image never feature men.

PMID- 8870599
TI  - Advertisements in the BMJ. BMJ should not carry advertisements for cars.

PMID- 8870600
TI  - Blood lead concentrations in United Kingdom have fallen substantially since 1984.

PMID- 8870601
TI  - Predicting which psychiatric patients are at risk of suicide. More information
      needs to be taken into account.

PMID- 8870602
TI  - Predicting which psychiatric patients are at risk of suicide. Care programme
      approach does not focus on need for services.

PMID- 8870603
TI  - Mental health teams should concentrate on psychiatric patients with greatest
      needs.

PMID- 8870604
TI  - Presentations of pituitary insufficiency and Addison's disease in insulin
      dependent diabetes may be similar.

PMID- 8870605
TI  - Government's expert group has reached consensus on prognosis of chronic fatigue
      syndrome.

PMID- 8870606
TI  - Magnetic resonance imaging is uncomfortable for patients.

PMID- 8870607
TI  - Annual meeting of the American Society of Anesthesiologists. New Orleans,
      Louisiana, October 19-23, 1996. Abstracts.

PMID- 8870608
TI  - A diagnosis/a natural history.

PMID- 8870609
TI  - Dyskinetic cerebral palsy: a clinical and genetic study.
AB  - The clinical features and family histories of 20 adults with dyskinetic cerebral
      palsy from 20 families were studied. The majority of the patients showed
      progressive neurological deterioration in adult life. In only three did the
      condition stabilise by 10 years of age and in seven there was deterioration after
      the age of 30. Two patients developed a secondary cervical spondylotic
      myelopathy. Four patients had affected relatives and there were similar
      proportions of affected parents and siblings. The family data suggest genetic
      heterogeneity with autosomal recessive and dominant variants. The existence of an
      X-linked form cannot be excluded, and the demonstration of an increased paternal
      age effect among single cases suggests that some of these may arise because of
      fresh dominant genetic mutation.

PMID- 8870610
TI  - IQ and its predictors in childhood hemiplegia.
AB  - In a population-based sample of 149 children with hemiplegia, IQ was highly
      correlated with a simple-to-calculate index of neurological severity. Performance
      IQ was an average of 13 points lower then verbal IQ-a difference that seemed to
      reflect specific visuospatial difficulties rather than an effect of the motor
      disability itself. Side of lesion was not significantly related to either IQ or
      verbal-performance discrepancy. Neurological factors and social class had
      additive effects on IQ, suggesting that neurological damage neither amplified nor
      obliterated the impact of ordinary psychosocial and genetic factors on IQ.

PMID- 8870611
TI  - ADHD, DAMP and other neurodevelopmental/psychiatric disorders in 6-year-old
      children: epidemiology and co-morbidity.
AB  - A total population of 589 6-year-old children were screened for
      neurodevelopmental/neuropsychiatric disorders by questionnaires to parents and
      preschool teachers, and by examination of motor abilities at the Child Health
      Center. Fifty screen-positive and fifty screen-negative children were assigned
      for complete neuropsychiatric assessment comprising a detailed history,
      psychiatric and neurodevelopmental assessment, neuropsychological examination and
      speech/language evaluation. Comprehensive diagnoses were made on the basis of all
      the available information. In the total population, 63 children (10.7%) with
      disorders were identified, 10 of whom had a diagnosis established before the
      study. The prevalence rates for deficits in attention, motor control and
      perception (DAMP) were 5.3 to 6.9%, for attention deficit hyperactivity disorder
      (ADHD) they were 2.4 to 4.0% and for mental retardation, 2.5%. Co-morbidity was
      established for ADHD on the one hand and DAMP, mental retardation and Tourette
      syndrome on the other. The findings suggest the need for a school entrant
      screening examination for the types of problems examined in this study.

PMID- 8870612
TI  - The stability and equivalence reliability of the functional independence measure
      for children (WeeFIM).
AB  - The reliability of the Functional Independence Measure for Children (WeeFIM) was
      examined in 37 non-disabled children and 30 children with disabilities, from 12
      to 76 months of age. The WeeFIM is derived from the Functional Independence
      Measure (FIM) and includes 18 items involving six functional subscales. Stability
      was assessed by administering the WeeFIM instrument to each child's caregiver on
      two occasions separated by 7 to 14 days. Intraclass correlation co-efficients
      (ICCs) for individual items ranged from 0.90 to 0.99. The ICC for the six WeeFIM
      subscales ranged from 0.94 for social cognition to 0.99 for transfers and
      locomotion. The ICC value for total WeeFIM test-retest reliability was 0.98 for
      children with disabilities and 0.99 for children without disabilities.
      Equivalence reliability was examined by comparing ratings obtained when using
      personal assessment with ratings collected during a telephone interview. No
      statistically significant differences were found for individual items, subscale
      scores or total WeeFIM values.

PMID- 8870613
TI  - School performance of ELBW children: a controlled study.
AB  - This paper examines the prevalence of learning difficulty in reading, spelling,
      mathematics and writing and the prevalence of attention deficit disorder (ADD) in
      extremely low-birthweight (ELBW) children at school compared to their peers.
      Parents of 87 eligible ELBW children completed an educational questionnaire and
      questionnaire for ADD. Teachers of the ELBW children completed a detailed
      educational and ADD questionnaire for the study child and two control children in
      the same class, matched for age and nearest in birth date to the study child.
      Parents reported that 4% of the ELBW children born between 1977 and 1986 were in
      a special education unit, 46% received remedial help and 21% repeated a grade.
      Teacher assessment of six aspects of reading and spelling and five aspects of
      mathematics and writing skills indicated that the ELBW children experienced
      marked problems in all areas compared to control children and were approximately
      3 times more likely to be delayed by more than a year in all areas. Prevalence of
      ADD was not increased in the ELBW children compared to the control group, though
      males in both groups had a higher prevalence of symptoms. Early intervention and
      special education resources must be available for ELBW children attending school.

PMID- 8870614
TI  - Behavioral problems in low-birthweight preschoolers.
AB  - Preschool behavior of a population-based sample of 144 5-year-old children with
      birthweights less than 2000g (LBW) was compared with a random sample of 163
      normal-birthweight term controls. The Personality Inventory for Children and the
      Yale Children's Inventory were completed by the mothers, and child behavior
      during psychometric testing was assessed. Nineteen per cent of the LBW children
      compared to 4% of controls had behavioral problems as defined by abnormal scores
      on more than three behavioral measures. The LBW children were more often socially
      insecure, anxious and difficult to manage, but inattention and hyperactivity were
      not prominent. The LBW children were not more sensitive to the negative impact of
      parental risk factors than normal-birthweight children.

PMID- 8870615
TI  - The neuropsychological profile of cri du chat syndrome without significant
      learning disability.
AB  - The clinical picture typically associated with cri du chat syndrome is one of
      profound intellectual impairment, severe motor delay and increased morbidity. In
      contrast to this picture, the present case report describes the cognitive and
      behavioural profile of a young female with cri du chat syndrome who displays no
      evidence of severe learning disability. Cognitive performance indicated good
      verbal skills with specific strengths on those tasks that require the ability to
      store and retrieve verbal information in comparison to poor non-verbal, spatial
      skills and weaknesses on those tasks that require multi-step manipulation of
      spatial stimuli and the ability to form whole percepts from fragmentary parts.
      The finding underlies the importance of assessing the wide range of cognitive
      potential of individuals with cri du chat syndrome.

PMID- 8870616
TI  - Magneto-encephalographical analysis of focal cortical heterotopia.
AB  - Focal cortical heterotopia is often associated with intractable seizures. Recent
      papers have reported that magnetic resonance imaging (MRI) demonstrates cortical
      heterotopia well compared with other imaging modalities, e.g. computed tomography
      scan. The authors analyzed the localization of epileptic spike foci of focal
      cortical heterotopia by 37 channel magnetoencephalography (MEG), and superimposed
      these dipoles on MRI. The estimated dipoles were observed to be located in a
      limited area, which corresponded to a focal cortical heterotopia on MRI. The
      present paper demonstrates that the combination of MEG and MRI is very
      advantageous for determination of the three dimensional localization of epileptic
      foci in patients with focal cortical heterotopia.

PMID- 8870617
TI  - Cerebellar hypoplasia in a patient with velo-cardio-facial syndrome.
AB  - Cerebellar malformations feature a large number of syndromes of unknown etiology.
      A child with hypoplasia of the vermis and left cerebellar hemisphere, severe
      mental retardation and facial dysmorphism was initially diagnosed as suffering
      from 3C (Ritscher-Schinzel) syndrome. A deletion in chromosome 22q11 was
      subsequently demonstrated, establishing the diagnosis of velo-cardio-facial
      (Shprintzen) syndrome. This observation confirms the previous finding of
      cerebellar anomalies in Shprintzen syndrome, and suggests an overlap between the
      VCFS and 3C syndrome. Other signs of VCFS should be looked for in children with
      cerebellar malformation.

PMID- 8870618
TI  - The orthopaedic history of spinal dysraphism. II. The modern surgical treatment.

PMID- 8870619
TI  - A novel relationship between O-antigen variation, matrix formation, and
      invasiveness of Salmonella enteritidis.
AB  - Salmonella enterica Enteritidis in chickens serves as a reservoir for
      salmonellosis in humans and the structure of its lipopolysaccharide (LPS) has
      been used to assess invasiveness. Culture from chick spleens generated colonies
      with an unusual wrinkled morphology, and it is designated the lacy phenotype. The
      characterize the nature of the morphological change, three isogenic variants were
      compared. Only the lacy phenotype produced a temperature-dependent cell surface
      matrix composed of several proteins in association with LPS high molecular weight
      O-antigen. Flagellin and a 35 kDa protein were identified as specific
      proteinaceous components of matrix. Both proteins cross-reacted with a monoclonal
      antibody previously determined to specifically detect the g-epitope of the
      Enteritidis monophasic flagella (H-antigen). These results suggest that O-antigen
      in association with protein contributes to cross-reactivity between molecules.
      The lacy phenotype was more organ invasive in 5-day-old chicks than isogenic
      variants producing low molecular weight O-antigen. However, it was no more
      efficient at contaminating eggs after oral inoculation of hens than a variant
      that completely lacked O-antigen, thus the lacy phenotype is classified as an
      intermediately invasive organism. The distinctive colonial phenotype of SE6
      E21lacy was used to investigate environmental factors that decreased O/C ratios
      and contributed to attenuation. In so doing, it was found that growth in
      complement at 46 degrees C caused matrix producing cells to hyperflagellate and
      migrate across agar surfaces. These results suggest that the structure of O
      antigen might influence the secretion and/or the function of Enteritidis cell
      surface proteins. The data also reveal a greater heterogeneity than has been
      assumed in the phenotype, and possibly the infectious behaviour, of Enteritidis.

PMID- 8870620
TI  - The application of genotyping techniques to the epidemiological analysis of
      Campylobacter jejuni.
AB  - Campylobacter jejuni serogroup reference strains and collections of sporadic and
      outbreak-associated isolates were examined for restriction fragment length
      polymorphisms (RFLPs), using C. jejuni random chromosomal and 16S rRNA gene
      probes. A collection of 48 Penner (HS) and 14 Lior (HL) serogroup reference
      strains, plus 10 clinical isolates, generated 35 RFLP and 26 ribotype patterns.
      In combination the two loci generated 48 distinct genotypes. Both probes were
      able to differentiate between certain random isolates of the same HS/HL
      serogroups but greater discrimination was obtained with RFLP than with
      ribotyping. Genotyping distinguished accurately between related and unrelated
      strains when applied to several outbreaks. Genotypic analysis of C. jejuni by
      restriction fragment length polymorphisms is a valuable technique for
      epidemiological typing. Chromosomal variation detected by the two unlinked probe
      loci provides some information about the genetic relationship between isolates.

PMID- 8870621
TI  - Epidemiological study on risk factors and risk reducing measures for
      campylobacter infections in Dutch broiler flocks.
AB  - From September 1991 until August 1993 an epidemiological study involving 20 Dutch
      broiler farms was conducted to identify risk factors and risk reducing measures
      for campylobacter infections in broiler flocks. Campylobacter spp. were detected
      in 64 (57%) of the 112 broiler flocks and in 25 (63%) of the 40 broiler cycles
      examined. Univariate analysis of farm management data was performed followed by
      logistic regression analysis of selected risk and risk reducing factors. The
      presence of other farm animals, including pigs, cattle, sheep and fowl, other
      than broilers, was found to be independently associated with an increased risk of
      campylobacter infections in broiler flocks (odds ratio (OR) = 11.81; P = 0.041).
      Further, the results indicate that application of specific hygiene measures
      during the rearing period, such as washing hands before tending the broiler
      flocks, the use of separate boots for each broiler house and the use of footbath
      disinfection when entering a broiler house, may significantly reduce the risk of
      campylobacter infections in broiler flocks.

PMID- 8870622
TI  - Prevalence and characteristics of Escherichia coli serotype O157:H7 and other
      verotoxin-producing E. coli in healthy cattle.
AB  - From February to July of 1994, 328 faecal samples from 32 herds were collected
      and verotoxin-producing Escherichia coli (VTEC) found on 84% of the farms. The
      proportion of animals infected varied from 0-63%. VTEC were recovered from 52
      (20%) of 257 cows and from 16 (23%) of 71 calves. Although the VTEC belonged to
      25 different serogroups, 7 (O8, O20, O22, O77, O113, O126 and O162) accounted for
      46% of strains. Nearly 45% of the strains. Nearly 45% of the 83 bovine VTEC
      strains belonged to serogroups associated with haemorrhagic colitis and
      haemolytic uraemic syndrome in humans. However, only 2 (2%) of 83 VTEC strains
      isolated from cattle belonged to enterohaemorrhagic E. coli (EHEC) serotypes
      (O26:H11 and O157:H7), and only 8 (10%) were positive for the attaching and
      effacing E. coli (eae) gene sequence. Polymerase chain reaction (PCR) showed that
      17 (20%) of VTEC strains carried VT1 genes, 43 (52%) possessed VT2 genes, and 23
      (28%) carried both VT1 and VT2 genes. Characterization of VTEC isolates revelated
      a heterogeneous population in terms of serogroup and toxin type in the positive
      herds. This study confirms that healthy cattle are a reservoir of VTEC, but, the
      absence of eae genes in most bovine VTEC strains suggests that they may be less
      virulent for humans than eae-positive EHEC.

PMID- 8870623
TI  - Risk factors for Neisseria meningitidis carriage in a school during a community
      outbreak of meningococcal infection.
AB  - As part of the management of an outbreak of meningococcal infection, 119 school
      contacts of an index case were swabbed for nasopharyngeal carriage. In a cohort
      study, risk factors for Neisseria meningitidis carriage were ascertained by means
      of a questionnaire, completed by 114 (96%) of those swabbed. Twenty five (21%)
      cultures were identified as "neisseria positive'; of which there were 18 (15%)
      Neisseria meningitidis isolates, 2 (2%) Neisseria lactamica isolates and 5 (4%)
      showed contaminants only. Two (2%) carriers were identified as harbouring the
      implicated outbreak strain. Single variable analysis identified six statistically
      significant risk factors for meningococcal carriage; increasing age, female sex,
      manual social class, personal smoking, regular attendance at a discotheque and
      rhinorrhoea. Multivariate analysis, using logistic regression modelling, found
      that of these six variables only age, sex and social class remained statistically
      significant when the other factors were controlled for. Nevertheless the role of
      smoking, social events and respiratory/viral infections in nasopharyngeal
      carriage, and other plausible mechanisms whereby age, sex and social class might
      exert their effect, could usefully be investigated further.

PMID- 8870624
TI  - Virulence of Staphylococcus epidermidis in a mouse model: significance of
      extracellular slime.
AB  - The ability to produce large quantities of biofilm on solid surfaces in vitro is
      believed to distinguish potentially pathogenic strains of Staphylococcus
      epidermidis from commensals. Biofilm consists of staphylococcal cells encased in
      a matrix of extracellular polysaccharide (also referred to as slime), firmly
      adherent to each other and to the underlying surface structure. The association
      of slime with colonization of catheter surfaces in vivo has been examined
      extensively. Less attention has been paid to the contribution of slime to
      infections that occur in the absence of an inserted device. In a mouse model of
      subcutaneous infection without an implanted device 10 S. epidermidis strains (5
      slime-positive, 5 slime-negative) produced abscesses; thus a foreign body is not
      essential for the expression of virulence by S. epidermidis. Biofilm-positive
      strains produced significantly more abscesses, that persisted longer than biofilm
      negative strains. In these chronic infections, large numbers of staphylococci
      were associated with macrophages and viable staphylococci were cultured from
      specimens of pus collected at autopsy. Thus slime or components of slime appear
      to delay the clearance of S. epidermidis from host tissues, possibly by
      interfering with intracellular killing mechanisms. However, differences in the
      capacity to produce abscesses, within both the slime-positive and slime-negative
      groups, indicate that other factors also contribute to the virulence of S.
      epidermidis.

PMID- 8870625
TI  - Seroprevalence of brucella antibodies among persons in high-risk occupation in
      Lebanon.
AB  - Prevalence of brucella-specific antibodies was measured in 597 persons in high
      risk occupations living in 10 regions of Lebanon using the standard agglutination
      test (SAT), anti-human globulin (Coombs') test (AHGT) and enzyme-linked
      immunosorbent assay (ELISA) for measuring immunoglobulin G (IgG), IgM and IgA.
      The study population consisted of butchers (54%), farmers (35%), laboratory
      technicians (8%), abbatoir workers (2%) and veterinarians (1%), with 82% males
      and 18% females. The overall seroprevalence based on SAT and AHGT titres of > or
      = 80 was 1.7% and 15%, respectively, but seroprevalence varied by region from 0
      5% in SAT and from 3.4-34% for AHGT. The overall seroprevalence based on ELISA
      IgG (OD > or = 0.6), IgM (OD > or = 0.6) and IgA (OD > or = 0.3) was 57, 61 and
      26%, respectively. The highest seroprevalence was noted in Biqaa (34%), Kisrwan
      (24%), Shouf (21%), Sidon (16%) and Aley (12%) regions. Nineteen percent of those
      surveyed reported symptoms that could be associated with brucellosis. We conclude
      that exposure to brucellosis is high among persons in high-risk occupations from
      all surveyed regions in Lebanon. Such findings should be used to design control
      measures especially now that the 17 years of civil strife is over.

PMID- 8870626
TI  - Genomic diversity of mec regulator genes in methicillin-resistant Staphylococcus
      aureus and Staphylococcus epidermidis.
AB  - Low-affinity penicillin-binding protein PBP-2a encoded by mecA is closely related
      to methicillin resistance in staphylococci, and expression of PBP-2a is
      controlled by regulator elements encoded by mecR1 and mecI which are located
      adjacent to mecA on the chromosome. Deletion or mutation which occurred in mec
      regulator gene is considered to be associated with constitutive production of PBP
      2a. The distribution of the mec regulator genes in 176 strains of Staphylococcus
      aureus and 33 strains of S. epidermidis isolated from a single hospital was
      studied by polymerase chain reaction amplification. Most clinical isolates of
      methicillin-resistant S. aureus (MRSA) (94.3%) and S. epidermidis (MRSE) (83.9%)
      possessed both mecI and mecR1 genes (type I), whereas no mec regulator genes were
      detected in mecA-negative isolates. In contrast, 7 MRSA and 5 MRSE isolates were
      found to have incomplete regulator genes, and they were classified into three
      groups; strains which lacked only mecI gene (type II), strains which lacked mecI
      and 3'-end of mecR1 gene (type III), and strains which lacked both regulator
      genes (type IV). Analysis of mecI gene from all the strains having mecI by
      restriction fragment length polymorphism after Mse I digestion indicated that
      three MRSA strains possessed one of the known point mutations identified
      previously. These findings indicated the predominance of a single type of MRSA
      possessing both mecI and mecR1 in the study period and also suggested a high
      genomic diversity in mec regulator region of staphylococci.

PMID- 8870627
TI  - Cryptosporidiosis in Wisconsin: a case-control study of post-outbreak
      transmission.
AB  - During March-April 1993, an estimated 403000 residents of the 5-county greater
      Milwaukee, Wisconsin area developed cryptosporidiosis after drinking contaminated
      municipal water. Although the number of cases dropped precipitously after the
      implicated water plant closed on 9 April, cases continued to occur. To
      investigate risk factors for post-outbreak cryptosporidiosis, 33 Milwaukee-area
      residents who had laboratory-confirmed Cryptosporidium infection with onset of
      diarrhoea between 1 May and 27 June 1993 were interviewed by telephone. Of these,
      28 (85%) had onset of diarrhoea during May, 12 (36%) had watery diarrhoea during
      the outbreak, and 5(15%) were HIV-infected. In a neighbourhood-matched case
      control study, immunosuppression (matched odds ratio (MOR) not calculable, 95%
      confidence interval (CI) 3.0, infinity) and having a child less than 5 years old
      in the household (MOR = 17.0, CI 2.0, 395.0) were independently associated with
      infection. When persons who had diarrhoea during the outbreak were excluded,
      immunosuppression remained significantly associated with illness (MOR not
      calculable, CI 1.6, infinity). Cryptosporidium transmission continued after this
      massive waterborne outbreak but decreased rapidly within 2 months.

PMID- 8870628
TI  - The UK register of HIV seroconverters: methods and analytical issues. UK register
      of HIV seroconverters (UKRHS) Steering Committee.
AB  - A Register of HIV-infected persons who have had a negative antibody test within 3
      years of their first antibody positive test (seroconverters) is being set up in
      the UK to monitor the distribution of times from HIV seroconversion to AIDS (the
      incubation period) and to death. It will also provide a national resource for use
      by those designing studies in this group of individuals. Clinicians caring for
      HIV-positive persons in Genito-Urinary Medicine, Infectious Disease and other
      departments throughout the UK were asked to participate by providing information
      on eligible subjects. Most laboratories undertaking HIV antibody testing were
      also contacted and asked to provide the name of the attending clinician for all
      seroconverters identified through the HIV laboratory reporting systems of the
      PHLS Communicable Disease Surveillance Centre (CDSC) and the Scottish Centre for
      Infection and Environmental Health (SCIEH) and for any other seroconverters known
      to them but not identified by CDSC or SCIEH. Data items sought for the Register
      include: sex, ethnic group, probable route of HIV transmission, annual CD4
      counts, details of therapy and prophylaxis prescribed, AIDS-defining events and
      vital status. Follow up information is collected annually. Wherever possible, all
      seroconverters known to a clinic have been identified, whether currently alive or
      dead, either from clinic records or laboratory reporting or both. The objective
      is to establish and update a complete register of seroconverters on a long-term
      to basis to provide reliable estimates of the incubation period on which future
      projections of AIDS cases in the UK can be made.

PMID- 8870630
TI  - The occurrence of hepatitis B and C viruses in Pakistani patients with chronic
      liver disease and hepatocellular carcinoma.
AB  - To study the occurrence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in
      patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in
      Pakistan, blood samples from 105 sequential patients with biopsy-proven CLD (n =
      82) and HCC (n = 23) were tested for HBV and HCV markers. Of the 105, 87 (83%)
      had evidence of hepatitis B exposure, 58 (55%) were positive for hepatitis B
      surface antigen (HBsAg), 23 (22%) had hepatitis C antibodies and 25 (24%) had
      detectable HCV RNA. Significantly more patients with HCC had evidence of HBV
      exposure in the absence of HCV markers (49/82 vs. 20/23, odds ratio 4.49, 95% CI
      1.17-25.16). The proportion of patients positive for HBsAg with no HCV markers
      was also significantly higher in the HCC group (34/82 vs. 18/23, odds ratio 5.08,
      95% CI 1.59-18.96). There were more patients with only HCV markers in the CLD
      group than the HCC group but the difference was not statistically significant
      (19/82 vs. 1/23, odds ratio 6.63, 95% CI 0.93-288.01). A modified non-isotopic
      restriction fragment length polymorphism study on PCR products was used to
      investigate the epidemiology of HCV genotypes in Pakistan. Due to depletion of
      the initial samples, a second series of specimens collected one year afterwards
      was used. Fifteen out of 40 samples had amplifiable product and all were
      identified as type 3. A commercial serological typing method on the same samples
      also confirmed that type 3 was the predominant HCV genotype in Pakistan.

PMID- 8870629
TI  - Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.
AB  - This paper uses meta-analysis of published data and a deterministic mathematical
      model of hepatitis B virus (HBV) transmission to describe the patterns of HBV
      infection in high endemicity areas. We describe the association between the
      prevalence of carriers and a simple measure of the rate of infection, the age at
      which half the population have been infected (A50), and assess the contribution
      of horizontal and perinatal transmission to this association. We found that the
      two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar
      prevalences of carriers and values of A50, and that there is a negative nonlinear
      relationship between A50 and the prevalence of carriers in high endemicity areas
      (Spearman's Rank, P = 0.0086). We quantified the risk of perinatal transmission
      and the age-dependent of infection to allow a comparison between the main hyper
      endemic areas. East Asia was found to have higher prevalences of HBeAg positive
      mothers and a greater risk of perinatal transmission from HBeAg positive mothers
      than sub-Saharan Africa, though the differences were not statistically
      significant. However, the two areas have similar magnitudes and age-dependent
      rates of horizontal transmission. Results of a simple compartmental model suggest
      that similar rates of horizontal transmission are sufficient to generate the
      similar patterns between A50 and the prevalences of carriers. Interrupting
      horizontal transmission by mass immunization is expected to have a significant,
      nonlinear impact on the rate of acquisition of new carriers.

PMID- 8870631
TI  - An outbreak of hepatitis A associated with a bakery, New York, 1994: the 1968
      "West Branch, Michigan' outbreak repeated.
AB  - In a community hepatitis A outbreak in the Rochester, New York area, 64 of 79
      (81%) people with anti-hepatitis A IgM-antibodies and onset of symptoms from 9
      April-31 May 1994, recalled eating food obtained from a retail buyer's club.
      Eleven (65%) of 17 households with cases contained club members compared with 7
      (21%) of 34 neighbourhood-matched control-households (matched odds ratio 8.5; 95%
      CI 1.7-41.6). Club employees who ate sugar-glazed baked goods were at fourfold
      increased risk for hepatitis. The source of infection was an IgM-positive baker
      who contaminated baked goods while applying sugar glaze. Computer-generated
      purchase lists implicated 11-12 March and 21-24 March as the most likely dates
      when contamination occurred. This investigation demonstrates the importance of
      food workers adhering to established hygiene practices. Computer-generated
      commercial datasets can be useful in epidemiologic investigations.

PMID- 8870632
TI  - Seroepidemiology of HTLV-I in relation to that of HIV-1 in the Gauteng region,
      South Africa, using dried blood spots on filter papers.
AB  - The seroprevalence of human T-lymphotropic virus type I (HTLV-I), in relation to
      that of human immunodeficiency virus type I (HIV-1), was determined in a
      comparative unlinked anonymous antenatal and neonatal (for indirect measurement
      of maternal antibodies) serosurvey in the Gauteng region of South Africa, using
      dried blood spots (DBS) and modified particle agglutination assays. Samples were
      confirmed to be antibody positive by western blot. A total of 2582 DBS collected
      during 1993 and 1994 from subjects of African, European and coloured origin were
      tested. Ten were confirmed as positive for HTLV-I and 128 for HIV-1. No
      antibodies to HTLV-I or HIV-1 were demonstrated in the 221 women of European and
      coloured origin who were screened. The HTLV-I seroprevalence rate in subjects of
      African origin appeared to increase from 0% in 1993 to 0.49% in 1994, while HIV-1
      seroprevalence rates of 5.2% and 5.4% were recorded for 1993 and 1994
      respectively. No significant differences in HTLV-I and HIV-1 seroprevalence rates
      were noted for the two areas investigated. These results indicate that HTLV-I
      should be included in infection control programs, and provide baseline data for
      monitoring the possible spread of HTLV-I in the heterosexual population in this
      region.

PMID- 8870634
TI  - Evidence of hantavirus in wild rodents in Northern Ireland.
AB  - A survey of evidence of rodent hantavirus infection in County Down, Northern
      Ireland was carried out by using immunofluorescence to detect virus antigen and
      antibody. Antibodies to hantavirus (R22 strain of Seoul virus and Hantaan 76-118)
      were found in 11/51 (21.6%) brown rats (Rattus norvegicus), 1/31 (3.2%) field
      mice (Apodemus sylvaticus) and 17/59 (28.8%) house mice (Mus domesticus). Seven
      rodents had evidence of hantavirus antigen in lung tissues. Antibody positive
      animals were significantly more likely to be adults than juveniles (P = 0.04) but
      and there was no sex difference between antibody positive and negative animals.
      House mice were more likely to be antibody positive if captured inside farm
      outbuildings (P = 0.08). Attempts to culture virus from the rodent material were
      unsuccessful. This work demonstrates a substantial rodent reservoir for
      hantavirus in Northern Ireland.

PMID- 8870633
TI  - Isotype-specific antibody responses to foot-and-mouth disease virus in sera and
      secretions of "carrier' and "non-carrier' cattle.
AB  - Isotype-specific antibody responses to foot-and-mouth disease virus (FMDV) were
      measured in the sera and upper respiratory tract secretions of vaccinated and
      susceptible cattle challenged with FMDV by direct contact or by intranasal
      inoculation. A comparison was made between cattle that eliminated FMDV and those
      that developed and maintained a persistent infection. Serological and mucosal
      antibody responses were detected in all animals after challenge. IgA and IgM were
      detected before the development of IgG1 and IgG2 responses. IgM was not detected
      in vaccinated cattle. Challenge with FMDV elicited a prolonged biphasic secretory
      antibody response in FMDV "carrier' animals only. The response was detected as
      FMDV-specific IgA in both mucosal secretions and serum samples, which gained
      statistical significance (P < 0.05) by 5 weeks after challenge. This observation
      could represent the basis of a test to differentiate vaccinated and/or recovered
      convalescent cattle from FMDV "carriers'.

PMID- 8870635
TI  - Antigenic and genetic analysis of equine influenza viruses from tropical Africa
      in 1991.
AB  - A detailed analysis of equine (H3N8) influenza viruses isolated in Nigeria during
      early 1991 has been undertaken. Antigenic analysis and the complete nucleotide
      sequence of the HA gene of three Nigerian equine influenza viruses
      A/eq/Ibadan/4/91, A/eq/Ibadan/6/91 and A/eq/Ibadan/9/91 are presented and limited
      sequence analysis of each of the genes encoding the internal polypeptides of the
      virus has been carried out. These results establish that, despite the
      geographical location from which these viruses were isolated, two were similar to
      the viruses which were concurrently causing disease in Europe in 1989 and 1991
      and were related to viruses that have been predominating in horses since 1985.
      The third was more closely related to viruses isolated from 1991 onward in Europe
      but also in other parts of the globe. A comparison of the nucleotide sequence of
      two of the viruses isolated in Nigeria (A/eq/Ibadan/4/91 and A/eq/Ibadan/6/91)
      with a European strain (A/eq/Suffolk/89) showed limited variation in the
      haemagglutinin gene which caused amino acid substitutions in one of the antigenic
      sites: this mutation resulted in the potential production of a new glycosylation
      site in antigenic site A. The other Nigerian virus (A/eq/Ibadan/9/91) showed only
      a single one amino acid change from another European strain
      (A/eq/Arundel/12369/91). The two distinct Nigerian viruses had several amino acid
      substitutions in the antigenic sites of the haemagglutinin glycoprotein.

PMID- 8870636
TI  - Foal diarrhoea between 1991 and 1994 in the United Kingdom associated with
      Clostridium perfringens, rotavirus, Strongyloides westeri and Cryptosporidium
      spp.
AB  - A case control study of foal diarrhoea in the United Kingdom was carried out over
      a 3-year period. Clostridium perfringens was significantly associated with foal
      diarrhoea (Odds Ratio (OR) = 3.0), being isolated from 57% of 421 animals with
      diarrhoea but from only 27% of 223 healthy foals. Also, C. perfringens was
      significantly associated with fatal diarrhoea (OR = 4.5). About half of diarrhoea
      with a fatal outcome was attributable to this organism. The other pathogens
      significantly associated with diarrhoea were rotavirus (OR = 5.6),
      Cryptosporidium spp. (OR = 3.2) and the nematode Strongyloides westeri, which was
      significant only when present in large numbers (> 2000 eggs/g of faeces: OR =
      6.1). Salmonella spp. (OR = 14.2) and Cryptosporidium spp. (OR = 3.0) were the
      only other pathogens associated with fatal illness. Overall, C. perfringens,
      rotavirus, and large numbers of Cryptosporidium spp. or S. westeri were isolated
      from 80% of foals with diarrhoea. Thermophilic Campylobacter spp., Yersinia
      enterocolitica, Escherichia coli and other parasites were not associated with
      diarrhoea. Carriage of C. perfringens, rotavirus and Cryptosporidium spp. was
      significantly greater in healthy foals in contact with cases of diarrhoea than in
      foals that were not in contact with diarrhoea (P < 0.05). There were no
      statistical interactions between any of the pathogens associated with diarrhoea
      although separate cases from one location often involved more than one pathogen.

PMID- 8870638
TI  - Genetic analysis of Clavibacter toxicus, the agent of annual ryegrass toxicity.
AB  - Multilocus enzyme electrophoresis was used to examine the relatedness of 52
      isolates of Clavibacter toxicus, the agent of annual ryegrass toxicity. These
      included 37 Western Australian (WA) field isolates sampled in 3 distinct
      locations over a 2-year period, and 15 isolates sampled from 6 different host
      plant species in 3 states in Australia over approximately 8 years. Seventeen
      reference strains for the related genera Curtobacterium, Rhodococcus and
      Arthrobacter were examined for comparison. The 69 isolates were divided into 29
      electrophoretic types (ETs), separated by genetic distances of 0.06 to 0.81. The
      C. toxicus isolates fell into 12 ETs, 11 of which formed a tightly clustered
      group separated by a genetic distance of 0.23 or less. Thirty-one of the WA field
      isolates of C. toxicus fell into a single ET, and four into another ET.
      Clavibacter toxicus therefore formed a closely related group which was
      genetically distinct from the other plant pathogenic species, and a dominant
      widely disseminated strain of the species was identified in WA.

PMID- 8870637
TI  - Restriction fragment length polymorphism of the pMJ101-like plasmid and
      ribotyping in the fish pathogen Vibrio ordalii.
AB  - A total of 32 Vibrio ordalii strains were studied for their plasmid content and
      shown to carry a plasmid of approximately 32 kb. This plasmid was subsequently
      subjected to restriction fragment length polymorphism (RFLP) studies. Using Hind
      III, three different restriction patterns were identified while BamH I cleaved
      the plasmid into a single linear fragment. The results suggest that the 32 kb
      plasmid is highly conserved but that some variation in restriction pattern
      occurs. The same set of strains was subjected to ribotyping. Using Mlu I, six
      different restriction patterns were demonstrated. Strains from the USA and Canada
      shared profiles with strains from Australia and Japan. Strains from Australia
      generated a single pattern whereas strains from North America were subdivided
      into three patterns, and the Japanese strains fell into five patterns. The
      results suggest that ribotyping in combination with RFLP studies of the pMJ101
      like plasmid may be useful in epidemiological studies of V. ordalii.

PMID- 8870639
TI  - Human parvovirus B19 infection within a family and risk for pregnant women.
AB  - During an outbreak of parvovirus B19 infection among four related families at
      least 70% of the household contacts, including a woman at the 33rd week of
      pregnancy, became infected. Twins were born at the 39th week of pregnancy, both
      with B19 infection. B19 DNA was detected in their sera by a nested PCR, anti-B19
      IgM was detectable only by an immunofluorescence assay, and low levels of
      maternal anti-B19 IgG were demonstrable by an immunoenzymatic test in the serum
      of both children. All the haematological parameters were normal at birth and 6
      months later, when B19 DNA and anti-B19 antibody were no longer detectable in
      serum samples. This observation emphasizes the high risk of B19 infection among
      household contacts and the possibility of a favourable outcome of the foetal
      infection, possibly related to infection late in the pregnancy.

PMID- 8870640
TI  - Cation-pi bonding and amino-aromatic interactions in the biomolecular recognition
      of substituted ammonium ligands.
AB  - Cation-pi bonds and amino-aromatic interactions are known to be important
      contributors to protein architecture and stability, and their role in ligand
      protein interactions has also been reported. Many biologically active amines
      contain substituted ammonium moieties, and cation-pi bonding and amino-aromatic
      interactions often enable these molecules to associate with proteins. The role of
      organic cation-pi bonding and amino-aromatic interactions in the recognition of
      small-molecule amines and peptides by proteins is an important topic for those
      involved in structure-based drug design, and although the number of structures
      determined for proteins displaying these interactions is small, general features
      are beginning to emerge. This review explores the role of cation-pi bonding and
      amino-aromatic interactions in the biological molecular recognition of amine
      ligands. Perspectives on the design of ammonium-ligand-binding sites are also
      discussed.

PMID- 8870641
TI  - Fibroblast growth factor-1 stimulation of quiescent NIH 3T3 cells increases G/T
      mismatch-binding protein expression.
AB  - Polypeptide growth factors promote cell-cycle progression in part by the
      transcriptional activation of a diverse group of specific genes. We have used an
      mRNA differential-display approach to identify several fibroblast growth factor
      (FGF)-1 (acidic FGF)-inducible genes in NIH 3T3 cells. Here we report that one of
      these genes, called FGF-regulated (FR)-3, is predicted to encode G/T mismatch
      binding protein (GTBP), a component of the mammalian DNA mismatch correction
      system. The murine GTBP gene is transiently expressed after FGF-1 or calf serum
      treatment, with maximal mRNA levels detected at 12 and 18 h post-stimulation. FGF
      1-stimulated NIH 3T3 cells also express an increased amount of GTBP as determined
      by immunoblot analysis. These results indicate that elevated levels of GTBP may
      be required during the DNA synthesis phase of the cell cycle for efficient G/T
      mismatch recognition and repair.

PMID- 8870642
TI  - Attenuation of oxidation and nitration reactions of peroxynitrite by
      selenomethionine, selenocystine and ebselen.
AB  - The effect of the selenium-containing compounds selenomethionine, selenocystine
      and ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] on the oxidation of
      dihydrorhodamine 123 caused by peroxynitrite and on the nitration of 4
      hydroxyphenylacetate by peroxynitrite was studied in comparison with their
      sulphur analogues methionine, cystine and ebsulfur [2-phenyl-1,2-benzisothiazol
      3(2H)-one]. The selenocompounds protected dihydrorhodamine 123 from oxidation and
      4-hydroxyphenylacetate from nitration more effectively than their sulphur
      analogues. Sodium selenite exhibited no effect. These observations are
      corollaries to the recent finding [Roussyn, Briviba, Masumoto and Sies (1996)
      Arch. Biochem. Biophys. 330, 216-218] that selenium-containing compounds are
      efficient in protecting against peroxynitrite-induced DNA single-strand breaks.

PMID- 8870643
TI  - Tumour necrosis factor-alpha-induced phosphorylation and activation of cytosolic
      phospholipase A2 are abrogated by an inhibitor of the p38 mitogen-activated
      protein kinase cascade in human neutrophils.
AB  - The role of the newly identified p38 mitogen-activated protein kinase (MAP
      kinase) in terminally differentiated cells, such as human neutrophils, is totally
      unknown. In order to examine the possible role of this MAP kinase in the
      phosphorylation and activation of cytoplasmic phospholipase A2 (cPLA2), we tested
      the effect of the recently synthesized inhibitor of p38 MAP kinase, SB 203580, on
      the phosphorylation and activation of both p38 MAP kinase and cPLA2. We found
      that while tumour necrosis factor-alpha (TNF-alpha)-stimulated tyrosine
      phosphorylation of p38 MAP kinase is affected only slightly by SB 203580, its
      stimulated kinase activity is greatly reduced in human neutrophils in suspension
      treated with this inhibitor. Furthermore, the TNF-alpha-stimulated
      phosphorylation and activation of cPLA2 are completely abolished in cells treated
      with SB 203580. Based on these data, it is reasonable to conclude that an SB
      203580-sensitive kinase, or kinases and/or phosphatases, are involved in the
      phosphorylation and activation of cPLA2 in intact human neutrophils in suspension
      stimulated by TNF-alpha. The possible role of the p38 MAP kinase cascade in the
      phosphorylation and activation of cPLA2 is discussed.

PMID- 8870644
TI  - Substrate protection against inactivation of the mammalian polyamine-transport
      system by 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide.
AB  - Mammalian polyamine transporters have not thus far been biochemically
      characterized. Since essential carboxy groups in the polyamine carrier might
      participate in the transport process, the ability of two different carbodi-imides
      to affect [3H]spermidine uptake was assessed in Chinese hamster ovary cells. Both
      the hydrophobic 1,3-dicyclohexylcarbodi-imide (DCC) and the more polar 1-ethyl-3
      (3-dimethylaminopropyl)carbodi-imide (EDC) irreversibly inhibited spermidine
      transport with EC50 values of 11 +/- 4 and 96 +/- 16 microM after 30 min at 22
      degrees C respectively. Prior treatment with EDC in the absence of substrate
      decreased both the Vmax and K(m) for spermidine uptake in a time- and
      concentration-dependent manner. Spermidine-transport inactivation by EDC (1 mM)
      was temperature-dependent, with 60 and 90% inhibition observed after 10 min at 22
      and 37 degrees C respectively. Spermine (10 microM) almost fully protected
      against spermidine-transport inactivation by EDC at 22 degrees C, and decreased
      the rate of inactivation at 37 degrees C by about 80%. Putrescine, spermidine and
      spermine were all effective in protecting against EDC-mediated inactivation of
      [3H]spermidine and [3H]putrescine uptake at 22 degrees C with EC50 values
      estimated at 10, 1 and less than 1 microM respectively. The nucleophile glycine
      ethyl ester (up to 50 mM) prevented the inhibition brought about by 1 mM EDC.
      Inhibition by 1 mM EDC was greater at pH 7.2 than at pH 5.8 (89 +/- 3 compared
      with 44 +/- 5%), whereas the converse was true for 100 microM DCC (81 +/- 3
      compared with 92 +/- 5%). On the other hand, spermine did not protect against
      inactivation of spermidine uptake by DCC. Moreover, DCC, but not EDC, inhibited
      Na(+)-dependent amino acid uptake. The present data indicate that (i) EDC and DCC
      inhibit polyamine transport through distinct mechanisms, (ii) substrate binding
      occludes one or several carboxy groups lying in a polar environment of the
      carrier and (iii) these carboxyl residues might be activated by EDC to crosslink
      a neighbouring nucleophile side group, resulting in a conformation of the
      polyamine carrier which is inactive for transport.

PMID- 8870645
TI  - Molecular cloning of a cDNA coding for GTP cyclohydrolase I from Dictyostelium
      discoideum.
AB  - The GTP cyclohydrolase I (GTP-CH) gene of the cellular slime mould Dictyostelium
      discoideum has been cloned and sequenced. The 855 bp cDNA of this gene contains
      the open reading frame (ORF) encoding 232 amino acids with a predicted molecular
      mass of approx. 26 kDa. Southern blot analysis indicated the presence of a single
      gene for GTP-CH in Dictyostelium. PCR amplification of the ORF from chromosomal
      DNA and sequencing showed the existence of a 101 bp intron in the GTP-CH gene of
      Dictyostelium discoideum. The amino acid sequence has 47% and 49% positional
      identity to those of the human and yeast enzymes respectively. Most of the
      sequence variation between species is located in the N-terminal part of the
      protein. The overall identity with the E. coli protein is markedly lower. The
      enzyme was expressed in E. coli and purified as a 68 kDa fusion protein with the
      maltose-binding protein of E. coli. GTP-CH of Dictyostelium is heat-stable and
      showed maximal activity at 60 degrees C. The Km value for GTP is 50 microM.

PMID- 8870646
TI  - Post-translational processing of the phosphatidylserine decarboxylase gene
      product in Chinese hamster ovary cells.
AB  - We have isolated a full-length cDNA clone of the Chinese hamster ovary (CHO) pssC
      gene, which encodes mitochondrial phosphatidylserine decarboxylase. The cDNA
      clone is capable of increasing phosphatidylserine decarboxylase activity to 11
      fold in CHO-K1 cells. The pssC gene product predicted from the cDNA sequence is
      composed of 409 amino acid residues. In an in vitro translation system coupled
      with in vitro transcription, the cDNA clone directs the formation of a protein
      with an apparent molecular mass of 46 kDa. In CHO-K1 cells, the cDNA clone leads
      to the production of two major peptides with apparent molecular masses of 38 and
      34 kDa, as determined by Western blotting with an antibody raised against a
      recombinant pssC protein. When CHO-K1 cells transfected with the cDNA clone are
      labelled with [35S]methionine for a short period, proteins immunoprecipitated
      with the antibody lack radioactive 38 and 34 kDa peptides, but contain two
      radioactive peptides with apparent molecular masses of 46 and 42 kDa instead. The
      pssC gene product predicted from the cDNA sequence has, near its C-terminus, a
      unique Leu-Gly-Ser-Thr sequence which is known as a processing site for
      Escherichia coli phosphatidylserine decarboxylase. A mutant pssC cDNA clone, in
      which Ser378 in the conserved sequence is replaced by Ala, leads to
      overproduction of 46, 42 and 38 kDa peptides, but not a 34 kDa peptide. This
      mutant clone is incapable of increasing phosphatidylserine decarboxylase
      activity, in contrast to the wild-type clone. These results indicate that the
      processing at the Leu-Gly-Ser-Thr sequence is essential for formation of the
      active enzyme. Thus, the pssC gene product is converted into mature
      phosphatidylserine decarboxylase through multiple steps of post-translational
      processing.

PMID- 8870647
TI  - Pervanadate activation of intracellular kinases leads to tyrosine phosphorylation
      and shedding of syndecan-1.
AB  - Syndecan-1 is a transmembrane haparan sulphate proteoglycan that binds
      extracellular matrices and growth factors, making it a candidate to act between
      these regulatory molecules and intracellular signalling pathways. It has a highly
      conserved transmembrane/cytoplasmic domain that contains four conserved
      tyrosines. One of these is in a consensus sequence for tyrosine kinase
      phosphorylation. As an initial step to investigating whether or not
      phosphorylation of these tyrosines is part of a signal-transduction pathway, we
      have monitored the tyrosine phosphorylation of syndecan-1 by cytoplasmic tyrosine
      kinases in intact cells. Tyrosine phosphorylation of syndecan-1 is observed when
      NMuMG cells are treated with sodium orthovanadate or pervanadate, which have been
      shown to activate intracellular tyrosine kinases. Initial studies with sodium
      orthovanadate demonstrate a slow accumulation of phosphotyrosine on syndecan-1
      over the course of several hours. Pervanadate, a more effective inhibitor of
      phosphatases, allows detection of phosphotyrosine on syndecan-1 within 5 min,
      with peak phosphorylation seen by 15 min. Concurrently, in a second process
      activated by pervanadate, syndecan-1 ectodomain is cleaved and released into the
      culture medium. Two phosphorylated fragments of syndecan-1 of apparent sizes 6
      and 8 kDa remain with the cell after shedding of the ectodomain. The 8 kDa size
      class appears to be a highly phosphorylated form of the 6 kDa product, as it
      disappears if samples are dephosphorylated. These fragments contain the C
      terminus of syndecan-1 and also retain at least a portion of the transmembrane
      domain, suggesting that they are produced by a cell surface cleavage event. Thus
      pervanadate treatment of cells results in two effects of syndecan-1: (i)
      phosphorylation of one or more of its tyrosines via the action of a cytoplasmic
      kinase(s) and (ii) cleavage and release of the ectodomain into the medium,
      producing a C-terminal fragment containing the transmembrane/cytoplasmic domain.

PMID- 8870649
TI  - Early response gene signalling in bryostatin-stimulated primary B chronic
      lymphocytic leukaemia cells in vitro.
AB  - The protein kinase C activator bryostatin induces differentiation and antagonizes
      the effects of tumour-promoting phorbol esters in a number of different cell
      types. We show here that bryostatin preferentially inhibits phorbol 12-myristate
      13-acetate (PMA)-induced proliferation compared with differentiation in a number
      of different B chronic lymphocytic leukaemia (BCLL) cell populations examined. By
      using a panel of 11 early-response gene probes in Northern hybridization
      analysis, we found that the profile of genes induced in response to bryostatin
      and PMA was qualitatively similar and displayed comparable sensitivities to
      inhibition with the serine-threonine kinase inhibitor 1-(5
      isoquinolinylsulphonyl)-2-methylpiperazine hydrochloride (H7), consistent with
      common signalling through protein kinase C. However, the nuclear oncogene. c-myc,
      which was induced strongly in response to PMA treatment, was only marginally up
      regulated by bryostatin. In addition, bryostatin selectively inhibited the
      magnitude of PMA-responsive induction of c-myc, to a degree commensurate with its
      antagonistic effects seen at the biological level. Finally, an anti-sense
      oligonucleotide blockade of c-myc inhibited PMA-induced proliferation but not the
      differentiation of BCLL cells, implicating this nuclear oncogene as an important
      determinant distinguishing PMA from bryostatin-coupled biological responses and
      also as a candidate third-messenger effector target for the anti-tumour effects
      of bryostatin.

PMID- 8870648
TI  - Purification and biochemical characterization of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid/kainate-sensitive L-glutamate receptors of pig brain.
AB  - Two preparations of glutamate receptors were purified from the synaptic junctions
      of pig brain by a combination of detergent solubilization, anion-exchange
      chromatography, wheat-germ agglutinin affinity chromatography and sedimentation
      through sucrose gradients. These preparations were enriched in specific L
      [3H]glutamate binding activity (> 5000 pmol of glutamate binding sites/mg of
      protein), and the rank order of ligand affinity for binding to these preparations
      was: quisqualate > 6-cyano-7- nitroquinoxaline-2,3-dione > alpha-amino-3-hydroxy
      5-methyl-4- isoxazolepropionic acid (AMPA) > L-glutamate > kainate > > N-methyl-D
      aspartate approximately L-2-amino-4-phosphonobutyrate. SDS/PAGE analysis revealed
      that more than 80% of the protein in either of these preparations appeared as a
      single protein band of 106 kDa. Two-dimensional gel electrophoresis further
      revealed that these 106 kDa proteins consisted of a series of acidic proteins
      which were recognized by antibodies against rat AMPA receptor subunits. These 106
      kDa proteins were also recognized by wheatgerm agglutinin and concanavalin A; in
      addition, peptide N-glycosidase F treatment of these preparations decreased their
      size to 99 kDa. Our results suggest that the putative glutamate receptors
      isolated here are likely to belong to the AMPA subtype of glutamate receptors in
      pig brain. Using the purification procedure reported here, 5 micrograms of AMPA
      receptor proteins can be isolated from 250 g of pig brain tissue.

PMID- 8870650
TI  - Biochemical isolation of a membrane microdomain from resting platelets highly
      enriched in the plasma membrane glycoprotein CD36.
AB  - Here we describe the isolation and characterization of a Triton X-100-insoluble
      fraction isolated from lysates of platelets by flotation in sucrose gradients.
      Transmission electron microscopy of the insoluble material revealed a
      heterogeneous population of vesicles ranging in size from 20 to 1000 nm, and
      Western blot analyses of platelet lysates for the caveolae structural coat
      protein, caveolin/VIP21, were negative. Biochemical characterization of the
      Triton X-100-insoluble fraction showed it to be cholesterol-rich, greatly and
      specifically enriched in the plasma membrane glycoprotein CD36, and also to
      contain Src and the Src-related kinase, Lyn. CD36 within this fraction is shown
      to be palmitoylated, but the fraction itself is not generally enriched in
      palmitoylated platelet proteins. These results suggest that this fraction
      represents caveolin-negative, CD36-rich microdomains in the resting platelet
      membrane. CD36 can form associations with certain Src-related kinases and can
      signal to activate platelets. These results suggest the possibility that such
      microdomains are implicated in platelet activation.

PMID- 8870651
TI  - Transformation of Rat-1 fibroblasts with the v-src oncogene induces inositol
      1,4,5-trisphosphate 3-kinase expression.
AB  - Transformation of Rat-1 fibroblasts with the v-src oncogene leads to a 6- to 8
      fold enhancement of the activity of the Ins(1,4,5)P3 3-kinase in cytosolic
      extracts [Johnson, Wasilenko, Mattingly, Weber and Garrison (1989) Science 246,
      121-124]. This study confirms these results using another v-src-transformed Rat-1
      cell line (B31 cells) and investigates the molecular mechanism by which pp60v-src
      activates Ins(1,4,5)P3 3-kinase. The mRNA and protein levels for two rat isoforms
      of Ins(1,4,5)P3 3-kinase were determined in the v-src-transformed cell line. Both
      the mRNA and protein levels for isoform A were elevated in v-src-transformed Rat
      1 cells while those for isoform B were not significantly affected. Moreover,
      stable expression of either form of Ins(1,4,5)P3 3-kinase in the B31 v-src
      transformed Rat-1 cell line did not result in tyrosine phosphorylation of
      Ins(1,4,5)P3 3-kinase A or B. These results suggest that at least one mechanism
      by which the v-src oncogene increases the activity of the Ins(1,4,5)P3 3-kinase
      in the Rat-1 transformed fibroblast is by increasing the level of expression of
      Ins(1,4,5)P3 3-kinase A.

PMID- 8870652
TI  - The gene G13 in the class III region of the human MHC encodes a potential DNA
      binding protein.
AB  - G13 is a single-copy gene lying approx. 75 kb centromeric of the complement gene
      cluster in the class III region of the human MHC. The gene spans approx. 17 kb of
      DNA and has been shown to encode mRNA of approx. 2.7 kb that is present in cell
      lines representing lymphoid and non-lymphoid tissues, indicating that it is
      ubiquitously expressed. The complete nucleotide sequence of the 2.7 kb mRNA has
      been derived from cDNA and genomic clones. The longest open reading frame
      obtained for G13 codes for a 703 amino acid protein of approx. 77 kDa in
      molecular mass. Comparison of the putative G13 amino acid sequence with the
      protein databases revealed significant similarities with DNA-binding proteins of
      the leucine zipper class, including a human cAMP response element binding
      protein. G13 contains a bZIP motif, a region rich in basic amino acids adjacent
      to a coiled-coil leucine zipper domain, common to this class of proteins that is
      known to be involved in dimerization and DNA binding. Antibodies raised against a
      fragment encoding the C-terminal half of the putative G13 protein recognized a
      major polypeptide of approx. 86 kDa and a minor polypeptide of approx. 78 kDa on
      immunoblotting of U937 cell extracts; this has been confirmed by
      immunoprecipitation experiments. Even though it contained at least one potential
      bipartite nuclear localization signal, the G13 protein was present both in the
      cytoplasm and the nucleus of the fibroblast cells. Thus G13 might be a novel DNA
      binding protein that is perhaps translocated to the nucleus in a regulated
      manner.

PMID- 8870653
TI  - Cloning and expression of a new HOXC6 transcript encoding a repressing protein.
AB  - Homeodomain-containing proteins are transcription factors that regulate the co
      ordinated expression of multiple genes involved in development, differentiation
      and malignant transformation. In an attempt to characterize expressed homeobox
      (HOX) genes in breast cancer cells, we cloned two distinct HOXC6 transcripts from
      an MCF7 cDNA library, Interestingly, one of them represents a new HOXC6 mRNA
      encoding a homeodomain-containing protein harbouring a unique N-terminal
      sequence. Moreover we demonstrate that this HOXC6 transcript is less abundant in
      human breast cancer cells than in non-tumorigenic cell lines, is detected in
      breast carcinomas and adjacent tissues and is expressed in a variety of human
      tumours. In addition, transient co-transfection experiments illustrated that both
      HOXC6 transcripts encode gene products that repress transcription from a HOX
      binding sequence in MDA-MB231 cells and co-operate with other HOX gene products
      such as HOXB7 on their target genes. Taken together, our results suggest that
      HOXC6 proteins might contribute to the breast cell phenotype through co-operative
      interactions with other HOX-derived proteins and repression of their target
      genes.

PMID- 8870654
TI  - Isolation and characterization of the gene encoding an aminopeptidase involved in
      the selective toxicity of ascamycin toward Xanthomonas campestris pv. citri.
AB  - An aminopeptidase gene named XAP has been isolated from Xanthomonas campestris
      pv. citri, a plant pathogenic bacterium. The bacterium is one of the rare micro
      organisms susceptible to ascamycin, an aminoacyl nucleoside antibiotic that
      inhibits protein synthesis. Sequence analysis reveals that the gene encodes a 311
      amino acid protein with a calculated molecular mass of 35134 Da and approx. 50%
      identity for amino acids to the proline iminopeptidase from Neisseria
      gonorrhoeae. The XAP gene product, Xap, expressed in Escherichia coli has proline
      iminopeptidase activity as well as ascamycin dealanylating activity in vitro.

PMID- 8870655
TI  - Inhibition of hsc70-catalysed clathrin uncoating by HSJ1 proteins.
AB  - The uncoating of clathrin-coated vesicles can be mediated in vitro by the
      'uncoating ATPase' that has been identified as the constitutive 70 kDa heat shock
      protein (hsp70), hsc70. It is now established that the activity of hsp70 proteins
      can be regulated by another family of molecular chaperones, the DnaJ family. In
      this study, we have investigated the effects of DnaJ-like proteins (the human
      neuron-specific proteins HSJ1a and HSJ1b) on clathrin uncoating. In order to
      measure the kinetics of clathrin release from coated vesicles, we have developed
      a quantitative, two-site ELISA for clathrin triskelions and demonstrated that
      stoichiometric amounts of HSJ1 proteins inhibit the initial burst of hsc70
      mediated clathrin uncoating by over 40%. This inhibition is not a consequence of
      ADP binding by hsc70 or the aggregation of hsc70, but correlates with an increase
      in the hsc70 associated with the coated vesicle fraction, suggesting that the
      inhibition is a consequence of a non-productive stabilization of hsc70 with a
      component of the coated vesicle fraction. These results strongly suggest that
      HSJ1 proteins interfere with an endogenous DnaJ-like protein that is involved in
      uncoating. Recent evidence suggests that the brain-specific vesicle-associated
      protein auxilin could play such a role. Although we find no evidence for auxilin
      in our coated vesicle preparation, our results predict that an auxilin-like
      protein will be a general factor in clathrin uncoating.

PMID- 8870656
TI  - Reconstitution of mammalian pyruvate dehydrogenase and 2-oxoglutarate
      dehydrogenase complexes: analysis of protein X involvement and interaction of
      homologous and heterologous dihydrolipoamide dehydrogenases.
AB  - Optimal conditions for rapid and efficient reconstitution of pyruvate
      dehydrogenase complex (PDC) activity are demonstrated by using an improved method
      for the dissociation of the multienzyme complex into its constituent E1
      (substrate-specific 2-oxoacid decarboxylase) and E3 (dihydrolipoamide
      dehydrogenase) components and isolated E2/X (where E2 is dihydrolipoamide
      acyltransferase) core assembly. Selective cleavage of the protein X component of
      the purified E2/X core with the proteinase arg C decreases the activity of the
      reconstituted complex to residual levels (i.e. 8-12%); however, significant
      recovery of reconstitution is achieved on addition of a large excess (i.e. 50
      fold) of parent E3. N-terminal sequence analysis of the truncated 35,000-M(r)
      protein X fragment locates the site of cleavage by arg C at the extreme N
      terminal boundary of a putative E3-binding domain and corresponds to the release
      of a 15,000-M(r) N-terminal fragment comprising both the lipoyl and linker
      sequences. In native PDC this region of protein X is shown to be partly protected
      from proteolytic attack by the presence of E3. Recovery of complex activity in
      the presence of excess E3 after arg C treatment is thought to result from low
      affinity interactions with the partly disrupted subunit-binding domain on X
      and/or the intact analogous subunit binding domain on E2. Contrasting recoveries
      for arg C-modified E2/X/E1 core, and untreated E2/E1 core of the 2-oxoglutarate
      dehydrogenase complex, reconstituted with excess bovine heart E3, pig heart E3 or
      yeast E3 point to subtle differences in subunit interactions with heterologous
      E3s and offer an explanation for the inability of previous investigators to
      achieve restoration of PDC function after selective proteolysis of the protein X
      component.

PMID- 8870657
TI  - Heterogeneity in utilization of N-glycosylation sites Asn624 and Asn138 in human
      lactoferrin: a study with glycosylation-site mutants.
AB  - Human lactoferrin (hLF) is a glycoprotein involved in the host defence against
      infection and excessive inflammation. Our objective was to determine to what
      extent each of the three sequons for N-linked glycosylation in hLF is actually
      used. Human kidney-derived 293(S) cell lines expressing recombinant hLF (rhLF) or
      glycosylation-site mutants were produced. The mutations involved replacement of
      asparagine residues with glutamine at one or more sequons for N-glycosylation
      (Asn138, Asn479 and Asn624). Comparative SDS/PAGE analyses of rhLF, mutated rhLF
      and human-milk-derived (natural) hLF led us to propose that glycosylation of hLF
      occurs at two sites (at Asn138 and Asn479) in approx. 85% of all hLF molecules.
      Glycosylation at a single site (Asn479) or at all three sites occurs in approx,
      5% and 9% of hLF respectively. The extent of glycosylation at Asn624 was
      increased to approx. 29% and 40% of Asn479 and Asn138/479 mutant molecules
      respectively, which indicates that glycosylation at Asn624 in natural hLF might
      be limited by glycosylation at Asn479. The presence in supernatant of
      unglycosylated hLF (approx. 60% of the total) after mutations of Asn138 and
      Asn479 suggests that glycosylation of hLF is not an absolute requirement for its
      secretion. The pronounced degradation of unglycosylated hLF in supernatant after
      mutation at all three glycosylation sites (Asn138/479/624 mutant) but not after
      mutation at both Asn138 and Asn479 suggests that an altered conformation rather
      than the lack of glycosylation has rendered the Asn138/479/624 mutant susceptible
      to intra- and/or extra-cellular degradation.

PMID- 8870658
TI  - Structural requirements for annexin I-S100C complex-formation.
AB  - S100C is a member of the S100 family of EF-hand-type Ca(2+)-binding proteins
      which are thought to bind to and thereby regulate the activity of cellular target
      proteins in a Ca(2+)-dependent manner. An intracellular ligand for S100C is the
      Ca2+/phospholipid-binding protein annexin I and we show here that complex
      formation is mediated through unique domains within S100C and annexin I. Using a
      proteolytically truncated annexin I derivative as well as a number of N-terminal
      annexin I peptides in liposome co-pelleting and ligand-blotting assays we map the
      S100C-binding site to the N-terminal 13 residues of annexin I. Similar analyses
      employing recombinantly expressed S100C mutants reveal that residues D91 to 194
      in the unique C-terminal extension of this S100 protein are indispensable for
      annexin I binding. Interaction between S100C and an N-terminal annexin I peptide
      containing a tryptoplan at position 11 can also be monitored by fluorescence
      emission spectroscopy after tryptophan excitation. This analysis indicates that
      the local environment of the tryptophan in annexin I becomes less aqueous on
      S100C binding, suggesting a hydrophobic nature of the protein-protein
      interaction. Thus the structural basis of the annexin 1-S100C complex-formation
      probably resembles to a large extent that of the well-characterized annexin II
      p11 interaction.

PMID- 8870659
TI  - The catalytic activity of the endoplasmic reticulum-resident protein microsomal
      epoxide hydrolase towards carcinogens is retained on inversion of its membrane
      topology.
AB  - Diol epoxides formed by the sequential action of cytochrome P-450 and the
      microsomal epoxide hydrolase (mEH) in the endoplasmic reticulum (ER) represent an
      important class of ultimate carcinogenic metabolites of polycyclic aromatic
      hydrocarbons. The role of the membrane orientation of cytochrome P-450 and mEH
      relative to each other in this catalytic cascade is not known. Cytochrome P-450
      is known to have a type I topology. According to the algorithm of Hartman,
      Rapoport and Lodish [(1989) Proc. Natl. Acad. Sci. U.S.A. 86, 5786-5790], which
      allows the prediction of the membrane topology of proteins, mEH should adopt a
      type II membrane topology. Experimentally, mEH membrane topology has been
      disputed. Here we demonstrate that, in contrast with the theoretical prediction,
      the rat mEH has exclusively a type I membrane topology. Moreover we show that
      this topology can be inverted without affecting the catalytic activity of mEH.
      Our conclusions are supported by the observation that two mEH constructs (mEHg1
      and mEHg2), containing engineered potential glycosylation sites at two separate
      locations after the C-terminal site of the membrane anchor, were not glycosylated
      in fibroblasts. However, changing the net charge at the N-terminus of these
      engineered mEH proteins by +3 resulted in proteins (++mEHg1 and ++mEHg2) that
      became glycosylated and consequently had a type II topology. The sensitivity of
      these glycosylated proteins to endoglycosidase H indicated that, like the native
      mEH, they are still retained in the ER. The engineered mEH proteins were
      integrated into membranes as they were resistant to alkaline extraction.
      Interestingly, an insect mEH with a charge distribution in its N-terminus similar
      to ++mEHg1 has recently been isolated. This enzyme might well display a type II
      topology instead of the type I topology of the rat mEH. Importantly, mEHg1,
      having the natural cytosolic orientation, as well as ++mEHg1, having an
      artificial huminal orientation, displayed rather similar substrate turnovers for
      the mutagenic metabolite benzo[a]pyrene 4,5-oxide. To our knowledge this is the
      first report demonstrating that topological inversion of a protein within the
      membrane of the ER has only a moderate effect on its enzymic activity, despite
      differences in folding pathways and redox environments on each side of the
      membrane. This observation represents an important step in the evaluation of the
      influence of mEH membrane orientation in the cascade of events leading to the
      formation of ultimate carcinogenic metabolites, and for studying the general
      importance of metabolic channelling on the surface of membranes.

PMID- 8870660
TI  - Characterization of a non-reducing terminal fragment from bovine articular
      cartilage keratan sulphates containing alpha(2-3)-linked sialic acid and alpha(1
      3)-linked fucose. A sulphated variant of the VIM-2 epitope.
AB  - Alkaline-borohydride-reduced keratan sulphate chains were isolated from bovine
      articular cartilage (6-8-year-old animals) and digested with keratanase II, an
      endo- beta-N-acetylglucosaminidase. The resulting oligosaccharides were
      borohydride-reduced and fractionated on a strong anion-exchange column. 1H-NMR
      spectroscopic analysis of the products revealed one containing both alpha(2-3)
      linked sialic acid and alpha(1-3)-linked fucose which was shown to have the
      structure (I) shown. This structure is a sulphated variant of the VIM-2 epitope
      (CD65), a putative ligand of E-selectin. No oligosaccharide containing the sialyl
      Le(+) structure [NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-] was
      identified in this study. [equation: see text]

PMID- 8870661
TI  - Theoretical studies on the control of oxidative phosphorylation in muscle
      mitochondria: application to mitochondrial deficiencies.
AB  - 1. The dynamic model of oxidative phosphorylation developed previously for rat
      liver mitochondria incubated with succinate was adapted for muscle mitochondria
      respiring on pyruvate. We introduced the following changes considering: (1) a
      higher external ATP/ADP ratio and an ATP/ADP carrier less displaced from
      equilibrium; (2) a substrate dehydrogenation more sensitive to the NADH/NAD+
      ratio; and (3) the respiratory chain, ATP synthase and phosphate carrier being
      more displaced from equilibrium. The experimental flux control coefficients
      already determined in state 3 for respiratory rate and ATP synthesis were used to
      adjust some parameters. This new oxidative phosphorylation model enabled us to
      simulate the whole titration curves obtained experimentally in state 3. These
      curves, which mimic the effect of mitochondrial complex deficiencies on oxidative
      phosphorylation, show a threshold effect, which is reproduced by the model. 2.
      the model was also used to simulate other physiological conditions such as (i)
      state 3.5, conditions in-between state 4 and state 3; and (ii) hypoxic
      conditions. In both cases a profound change in the pattern of the control
      coefficients was shown. 3. This model was thus found useful in investigating a
      variety of new conditions, the most interesting of which can then be
      experimentally studied.

PMID- 8870662
TI  - Association of insulin-degrading enzyme with a 70 kDa cytosolic protein in
      hepatoma cells.
AB  - We have investigated the biosynthesis, subcellular location and expression of
      insulin-degrading enzyme (IDE). a type-I peroxisomal protease, in semi
      permeabilized hepatoma cells using pulse-chase experiments, non-denaturing
      immunoprecipitation protocols and Northern-blot analyses. In HcpG2 cell lysates
      prepared from cells radiolabelled with Tran[35S]-label, immunoprecipitated IDE
      was observed immediately after a 5 min pulse and subsequently declined during
      chase with t1/2 of approx. 33 h. In addition to the 110 kDa IDE protein, a
      protein of 70 kDa (p70) was identified in radiolabelled immunoprecipitates when
      using a monoclonal anti-IDE antibody 9B12 under non-denaturing conditions. This
      same antibody did not recognize p70 on Western blots of whole-cell lysates nor in
      sequential immunoprecipitates of immunocomplex-bead eluates from anti-IDE
      immunoprecipitations. Likewise, cross-linking studies performed on intact HepG2
      and H35 hepatoma cells in vivo revealed the existence of a hetero-oligomeric
      complex of 180 kDa in which IDE and p70 were physically associated. Digitonin
      permeabilization studies in normal and 35S-labelled HepG2 cells have defined a
      predominant association of IDE and its associated protein p70 with cytosol
      (supernatant); only a minor amount of the protein IDE was detected in peroxisomes
      (cellular pellet). Immunoprecipitation of IDE from 35S-labelled cell lysates of
      normal and stably transfected Chinese hamster ovary cells overexpressing IDE
      failed to detect p70. Treatment of HepG2 cells with clofibrate, a peroxisome
      proliferator, resulted in a dose-dependent increase of the two human IDE
      transcripts of 3.6 and 3.2 kb. This effect was not accompanied by a similar
      change at the protein level, nor by a change in the subcellular location of the
      proteins IDE and p70. Based on these findings we propose that in hepatoma cells:
      (1) IDE mainly exists in a stable cytoplasmic pool that is unchanged in cells
      undergoing peroxisomal proliferation; and (2) p70 binding to IDE may serve to
      maintain the dual cytosolic and peroxisomal pools of IDE in a stable equilibrium.

PMID- 8870663
TI  - Role of lysine, tryptophan and calcium in the beta-elimination activity of a low
      molecular-mass pectate lyase from Fusarium moniliformae.
AB  - An extracellular pectate lyase from Fusarium moniliformae was purified to
      homogeneity by affinity chromatography followed by gel filtration, with a yield
      of 76.5%. Laser desorption MS of the enzyme gave a molecular mass of 12,133.5 +/-
      2.5 Da. The pectate lyase was a glycoprotein with a 5% carbohydrate content and
      had a pl value of 9.1. Atomic-emission spectrometry showed that Ca2+ was a part
      of the holoenzyme held by carboxy groups of the protein. These results support
      the hypothesis of a putative Ca2+ site suggested by Yodder, Keen and Jurnak
      [(1993) Science 260, 1503-1507] in the crystal structure of pectate lyase C of
      Erwinia chrysanthemi. Loss of Ca2+ was observed by treatment with EGTA or carboxy
      modifying Woodward's reagent K, with subsequent loss of enzyme activity.
      Tryptophan fluorescence quenching showed that Ca2+ does not affect binding of
      substrate to enzyme. Chemical-modification and substrate-protection studies
      showed the presence of lysine and tryptophan at or near the active site of the
      pectate lyase. Chemically modified enzyme showed no major structural changes as
      determined by CD. Amino acid analyses of native, trinitrobenzenesulphonate (TBNS)
      treated and substrate-protected TNBS-treated enzyme showed that a single
      essential residue of lysine is present at or near the active-site. Substrate
      affinity studies showed that tryptophan could be essential for substrate binding,
      whereas lysine could be involved in the catalysis. Fluorescence quenching further
      confirmed the involvement of tryptophan in substrate binding. The reaction
      mechanism involving beta-elimination by this enzyme is discussed.

PMID- 8870664
TI  - Distinct biochemical properties of the native members of the G12 G-protein
      subfamily. Characterization of G alpha 12 purified from rat brain.
AB  - G12 and G13 are insufficiently characterized pertussis toxin-insensitive G
      proteins. Here, we describe the isolation of G alpha 12 from rat brain membranes.
      G alpha 12 was purified to apparent homogeneity by three steps of conventional
      chromatography, followed by two cycles of subunit-exchange chromatography on
      immobilized G subunits. Purified G alpha 12 bound guanosine 5'-[gamma
      thio]triphosphate slowly and substoichiometrically. For isolation of functionally
      active G alpha 12, it was mandatory to use sucrose monolaurate as a detergent.
      Comparative studies of both rat-brain-derived members of the G12 subfamily
      revealed differences in the affinity of G alpha 12 and G alpha 13 for G beta
      gamma. G alpha 12 required a higher Mg2+ concentration for AlF4- -induced
      dissociation from immobilized G beta gamma than did G alpha 13. In addition, the
      G12 subfamily members differed in their sedimentation velocities, as determined
      by sucrose-density-gradient centrifugation. Analysis of sedimentation
      coefficients revealed a higher tendency of G12 to form supramolecular structures
      in comparison to G13 and other G-proteins. These G13 structures were stabilized
      by sucrose monolaurate, which in turn may explain the necessity for this
      detergent for purification of functionally active G alpha 12. Despite these
      distinct biochemical characteristics of G12 and G13, both purified G-proteins
      coupled to a recombinant thromboxane A2 (TXA2) receptor reconstituted into
      phospholipid vesicles. These data indicate, (1) significant differences in the
      biochemical properties of native members of the G12 subfamily, and (2) their
      specific coupling to TXA2 receptors.

PMID- 8870665
TI  - G-protein inhibition of phospholipase C-beta 1 in membranes: role of G-protein
      beta gamma subunits.
AB  - Rat liver plasma membranes reconstituted with bovine brain phospholipase C beta 1
      (PLC- beta 1) exhibit a dual regulation of PLC- beta 1 activity by G-proteins.
      Guanosine 5'-[gamma-thio]triphosphate (GTP[S]; 0.1 nM) produced a 20-25%
      inhibition of PLC- beta 1 activity within 7 min of incubation. The addition of
      vasopressin resulted in near-basal levels of activity in the presence of 0.1 nM
      GTP[S]. Clonidine had little effect on the net inhibition due to GTP[S]. A
      similar antagonism between carbachol and GTP[S] occurred in cerebral cortical
      membranes containing endogenous PLC- beta 1 activity. alpha 0/i-GDP (a mixture of
      GDP-liganded G0 alpha and Gi alpha) attenuated the GTP[S]-dependent inhibition of
      PLC- beta 1 whereas alpha 0/i-GTP[S] had no effect, suggesting an involvement of
      G-protein beta gamma subunits in the inhibition of PLC- beta 1. Low
      concentrations of beta gamma subunits inhibited PLC- beta 1 activity. Inhibition
      was followed by reversal to basal activity and onset of stimulation as the beta
      gamma concentration was increased. Inhibition by beta gamma was dependent on the
      presence of membranes. These results indicate that G-protein beta gamma subunits
      constitute a mechanism by which G-protein mediate a rapid and transient
      inhibition of PLC- beta 1.

PMID- 8870666
TI  - Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4
      gene transcription in 3T3-L1 adipocytes.
AB  - We have previously demonstrated that chronic exposure of 3T3-L1 adipocytes to
      tumour necrosis factor-alpha (TNF) resulted in a marked decrease (approximately
      90%) in cellular GLUT4 (insulin-responsive glucose transporter) mRNA content as a
      result of a decreased transcription rate of the GLUT4 gene (approximately 75%)
      and a reduced half-life of its mRNA (9 to 4.5 h). Investigation of the signalling
      mechanism responsible for this regulation demonstrated that in the 3T3-L1
      adipocytes, sphingomyelin levels decreased to 50% of control levels within 40 min
      of exposure to TNF, consistent with activation of a sphingomyelinase. In the same
      manner as with TNF, treatment of the adipocytes with 1-3 microM C6-ceramide, a
      membrane-permeable analogue of ceramide, decreased GLUT4 mRNA content by
      approximately 60%. Subsequent investigations revealed that transcription of the
      GLUT4 gene was reduced by approximately 65% in response to C6-ceramide,
      demonstrating that the decrease in mRNA content is mediated by a reduction in the
      transcription of the genc. No effect on GLUT4 mRNA stability was observed after
      exposure of the adipocytes to C6-ceramide. These observations are interesting in
      light of our previous data demonstrating that TNF affects both GLUT4
      transcription and mRNA stability in the 3T3-L1 adipocytes. In conclusion, the
      effect of ceramide on GLUT4 gene expression is at the level of transcription,
      suggesting that another pathway controls mRNA stability. These data establish
      that ceramide-initiated signal transduction pathways exist within the adipocyte,
      and provide a potential mechanism for control of GLUT4 gene expression.

PMID- 8870667
TI  - Post-transcriptional regulation of H-ferritin gene expression in human monocytic
      THP-1 cells by protein kinase C.
AB  - The mRNA coding for H-ferritin was highly induced in human monocytic THP-1 cells
      following treatment with phorbol 12-myristate 13-acetate (PMA). The induction was
      detected at 3 h, reached maximal levels at 12 h, and was sustained for up to 48 h
      subsequent to PMA exposure. PMA-induced up-regulation of H-ferritin gene
      expression was also observed in other leukaemic cell lines, HL60 and U937, but
      not in non-leukaemic cell types, including human fibroblasts, endothelial cells
      and smooth muscle cells. The effect of PMA could be completely blocked by the
      protein kinase C inhibitor, H-7. Furthermore, treatment of THP-1 cells with
      bacterial phospholipase C also produced a marked increase in expression of H
      ferritin mRNA, suggesting the activation of protein kinase C was responsible for
      the accumulation of mRNA. Nuclear run-off experiments demonstrated that PMA did
      not increase the transcriptional rate of the H-ferritin gene. In contrast, the
      half-life of the H-ferritin mRNA measured in the presence of actinomycin D was
      greatly prolonged in PMA-treated cells. The induction of H-ferritin mRNA by PMA
      required no protein synthesis. Conversely, treatment of THP-J cells with protein
      synthesis inhibitor, cycloheximide, resulted in a 4-5-fold increase in H-ferritin
      mRNA. The increase in the stability of the H-ferritin mRNA was also observed in
      cells treated with cycloheximide. Taken together, these results suggest that the
      stability of H-ferritin mRNA in THP-1 is subjected to regulation via a protein
      kinase C-mediated phosphorylation on existing putative protein factor(s).

PMID- 8870668
TI  - High-yield production of functionally active human serum transferrin using a
      baculovirus expression system, and its structural characterization.
AB  - Recently, there has been much interest in expressing recombinant human serum
      transferrin (HST) and mutants thereof for structural and functional studies. We
      have developed a baculovirus expression system for the rapid and efficient
      production of large quantities of HST (> 20 mg/l). Like native HST, the
      recombinant protein can bind two ferric ions in the presence of bicarbonate, and
      is actively taken up by receptor-mediated endocytosis. Secondary structure
      calculations from CD measurements indicate a content of 42% alpha-helix and 28%
      beta-sheet. This is the first reported use of a non-mammalian expression system
      to produce functional HST, and will provide a practical tool to allow expression
      of a wide range of HST variants for mutagenesis studies.

PMID- 8870669
TI  - Molecular cloning and expression in COS-1 cells of pig kidney aminopeptidase P.
AB  - Aminopeptidase P (AP-P; X-Pro aminopeptidase; EC 3.4.11.9), a key enzyme in the
      metabolism of the vasodilator bradykinin, has been cloned from a pig kidney
      cortex cDNA library following the use of the PCR to identify sub-libraries
      enriched in AP-P clones. The complete primary sequence of the enzyme has been
      deduced from a full-length cDNA clone. This predicts a protein of 673 amino acids
      with a cleavable N-terminal signal sequence and six potential N-linked
      glycosylation sites. A stretch of mainly hydrophobic amino acids at the C
      terminus is predicted to co-ordinate the attachment of a glycosyl
      phosphatidylinositol (GPI) membrane anchor. Although AP-P is a zinc
      metallopeptidase, the predicted primary sequence does not contain any
      recognizable zinc-binding motif. Transient expression of AP-P cDNA in COS-1 cells
      resulted in enzymic activity characteristic of AP-P, namely apstatin- and EDTA
      sensitive hydrolysis of bradykinin and Gly-Pro-Hyp. The expressed protein was
      recognized as a polypeptide of M(r)91,000 under reducing conditions, following
      immunoblotting of COS-1 membranes with a polyclonal antibody raised against
      purified pig kidney AP-P. The presence of a GPI anchor on expressed AP-P was
      established by demonstrating release of the enzyme from a membrane fraction
      following treatment with bacterial phosphatidylinositol-specific phospholipase C
      and its corresponding conversion from an amphipathic to a hydrophilic form, as
      assessed by phase separation in Triton X-114. Sequence comparisons confirm that
      AP-P is a member of the proline peptidase family of hydrolytic enzymes and is
      unrelated in sequence to other brush-border membrane peptidases.

PMID- 8870670
TI  - Y-box proteins interact with the S1 nuclease-sensitive site in the chicken alpha
      2(I) collagen gene promoter.
AB  - The sequence of the chicken alpha 2(I) collagen promoter from -712 to -85,
      relative to exon 1, has been shown to be important for transcriptional activity.
      Within this region a pyrimidine/purine asymmetrical element at -200 bp forms an
      in vitro S1 nuclease-sensitive site. The pyrimidine-rich strand of this element
      interacts specifically with single-stranded DNA-binding proteins present in
      fibroblast nuclear extracts [Bayarsaihan and Lukens (1996) Biochem. J. 314, 293
      296]. To identify these proteins we performed expression screening of a chick
      embryo fibroblast cDNA library using a single-stranded polypyrimidine sequence
      derived from this element. One of the isolated clones was found to encode a
      member of the cold-shock gene family, either chicken YB-1 or a highly homologous
      protein. This protein and a known chicken Y-box protein were both found to bind
      sequence-specifically to the pyrimidine-rich strand of the pyrimidine/purine
      asymmetrical element in the chicken alpha 2(I) collagen promoter. The binding
      mechanism of these proteins could be based on the formation of a non-canonical
      triplex DNA structure (H-DNA). Although members of this widespread and conserved
      protein family have been reported to modulate the expression of a number of
      genes, the findings reported here provide the first evidence for a possible role
      of cold-shock proteins in the regulation of type I collagen genes.

PMID- 8870671
TI  - Characterization of a rat liver Golgi sulphotransferase responsible for the 6-O
      sulphation of N-acetylglucosamine residues in beta-linkage to mannose: role in
      assembly of sialyl-galactosyl-N-acetylglucosamine 6-sulphate sequence of N-linked
      oligosaccharides.
AB  - Rat liver Golgi membranes were found to contain an enzyme that can transfer
      sulphate from 3'-phosphoadenosine 5'-phosphosulphate (PAPS) to C-6 of the
      terminal GlcNAc in beta-linkage to mannose and has properties indicating that it
      is involved in the synthesis of the NeuAc alpha 2-3(6)Gal beta 1-4GlcNAc(6-SO4)
      sequences observed in the N-linked carbohydrate units of various glycoproteins.
      Assays performed with [35S]PAPS (Km 0.67 microM) and GlcNAc beta 1-6Man alpha 1-O
      Me (GnMaMe) acceptor (Km 0.71 mM) indicated that the sulphotransferase had a pH
      optimum of approx. 7.0 and is markedly stimulated by Mn2+ ions (maximum approx.
      15 mM) and Triton X-100 (0.05-0.1%). Hydrazine/nitrous acid/NaBH4 treatment of
      the 35S-labelled product yielded radiolabelled 2,5-anhydromannitol(6-SO4). The
      sulphated GnMaMc product of the GlcNAc-6-O-sulphotransferase could be
      galactosylated by a rat liver Golgi enzyme that was shown to have the same
      properties as the UDP-Gal:GlcNAc beta-1,4-galactosyltransferase from bovine milk.
      Competition studies performed with GlcNAc and GlcNAc-6-SO4 furthermore indicated
      that the same liver enzyme acted on both acceptors to produce Gal beta 1-4GlcNAc
      and Gal beta 1-4GlcNAc(6-SO4) with Km values of 1.04 and 1.68 mM respectively.
      Because the sulphated N-acetyl-lactosaminc could in turn serve as an acceptor for
      rat liver sialyltransferase, it seems that this enzyme, together with the Golgi
      galactosyltransferase and the GlcNAc-6-O-sulphotransferase, could act in concert
      in assembling the NeuAc alpha 2-3(6)Gal beta 1-4GlcNAc(6-SO4) branches of complex
      N-linked oligosaccharides.

PMID- 8870672
TI  - Time-course studies by synchrotron X-ray solution scattering of the structure of
      human low-density lipoprotein during Cu(2+)-induced oxidation in relation to
      changes in lipid composition.
AB  - Low-density lipoproteins (LDLs) in plasma are constructed from a single molecule
      of apolipoprotein B-100 (apoB) (M(r) 512,000) in association with lipid
      [approximate M(r) (2-3) x 10(6)]. LDL oxidation is an important process in the
      development of atherosclerosis, and can be imitated by the addition of Cu2+ ions.
      Synchrotron X-ray scattering of LDL yields curves without radiation damage
      effects at concentrations close to physiological. The radius of gyration RG for
      preparations of LDL from different donors ranged between 12.1 and 16.0 nm, with a
      mean of 13.9 nm. At 4 degrees C, the distance distribution curve P(r) indicated a
      maximum dimension of 25-27 nm for LDL, a peak at 19.5 nm which corresponds to a
      surface shell of protein and phospholipid head groups in LDL, and submaxima
      between 1.7 and 13.5 nm, which correspond to an ordered lipid core in LDL. LDL
      from different donors exhibited distinct P(r) curves. For oxidation studies of
      LDL by X-rays, data are best obtained at 4 degrees C at a concentration of > or =
      2 mg of LDL protein/ml together with controls based on non-oxidized LDL. LDL
      oxidation (2 mg of apoB/ml) was studied at 37 degrees C in the presence of 6.4,
      25.6 and 51.2 mu of Cu2+/g of apoB. Large changes in P(r) were reproducibly
      observed in the inter-particle distance range between 13 and 16 nm shortly after
      initiation of oxidation. This corresponds to the phospholipid hydrocarbon in LDL,
      which has either increased in electron density during oxidation or become
      increasingly disordered. After 25 h, the structural changes subsequently spread
      to regions of the P(r) curves assigned to surface apoB and the central core of
      cholesteryl esters and triacyl-glycerols. Lipid analyses were carried out under
      the same solution conditions. The alpha-tocopherol and beta-carotene antioxidant
      contents of LDL were consumed within 1-2 h. Analyses of the formation of
      thiobarbituric acid-reactive substances and lipid hydroperoxides indicated that
      arachidonic acid was preferentially oxidized before the maximal formation of
      lipid hydroperoxides at 8-12 h after initiation of oxidation. High-performance
      TLC showed that phosphatidylcholine was continuously converted into
      lysophosphatidylcholine during oxidation, which is consistent with the early
      changes in the X-ray P(r) curves. The neutral core lipids became modified only
      after 12-15 h of oxidation. The combination of X-ray scattering structural
      analyses with biochemical analyses shows that the oxidation of LDL first affects
      the outer shell of surface phospholipid, then it spreads towards damage of apoB
      and the internal neutral lipid core of LDL.

PMID- 8870673
TI  - Predicted alpha-helix/beta-sheet secondary structures for the zinc-binding motifs
      of human papillomavirus E7 and E6 proteins by consensus prediction averaging and
      spectroscopic studies of E7.
AB  - The E7 and E6 proteins are the main oncoproteins of human papillomavirus types 16
      and 18 (HPV-16 and HPV-18), and possess unknown protein structures. E7 interacts
      with the cellular tumour-suppressor protein pRB and contains a zinc-binding site
      with two Cys-Xaa2-Cys motifs spaced 29 or 30 residues apart. E6 interacts with
      another cellular tumour-suppressor protein p53 and contains two zinc-binding
      sites, each with two Cys-Xaa2-Cys motifs at a similar spacing of 29 or 30
      residues. By using the GOR I/III, Chou-Fasman, SAPIENS and PHD methods, the
      effectiveness of consensus secondary structure predictions on zinc-finger
      proteins was first tested with sequences for 160 transcription factors and 72
      nuclear hormone receptors. These contain Cys2His2 and Cys2Cys2 zinc-binding
      regions respectively, and possess known atomic structures. Despite the zinc- and
      DNA-binding properties of these protein folds, the major alpha-helix structures
      in both zinc-binding regions were correctly identified. Thus validated, the use
      of these prediction methods with 47 E7 sequences indicated four well-defined
      alpha-helix (alpha) and beta-sheet (beta) secondary structure elements in the
      order beta beta alpha beta in the zinc-binding region of E7 at its C-terminus.
      The prediction was tested by Fourier transform infrared spectroscopy of
      recombinant HPV-16 E7 in H2O and 2H2O buffers. Quantitative integration showed
      that E7 contained similar amounts of alpha-helix and beta-sheet structures, in
      good agreement with the averaged prediction of alpha-helix and beta-sheet
      structures in E7 and also with previous circular dichroism studies. Protein fold
      recognition analyses predicted that the structure of the zinc-binding region in
      E7 was similar to a beta beta alpha beta motif found in the structure of Protein
      G. This is consistent with the E7 structure predictions, despite the low sequence
      similarities with E7. This predicted motif is able to position four Cys residues
      in proximity to a zinc atom. A model for the zinc-binding motif of E7 was
      constructed by combining the Protein G coordinates with those for the zinc
      binding site in transcription factor TFIIS. Similar analyses for the two zinc
      binding motifs in E6 showed that they have different alpha/beta secondary
      structures from that in E7. When compared with 12 other zinc-binding proteins,
      these results show that E7 and E6 are predicted to possess novel types of zinc
      binding structure.

PMID- 8870674
TI  - Thyromimetic mode of action of peroxisome proliferators: activation of 'malic'
      enzyme gene transcription.
AB  - Peroxisome proliferators induce thyroid-hormone-dependent liver activities, e.g.
      'malic' enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, glucose-6
      phosphate dehydrogenase, S14[Hertz, Aurbach, Hashimoto and Bar-Tana (1991)
      Biochem. J. 274, 745-751]. Here we report that the thyromimetic effect of
      peroxisome proliferators with respect to 'malic' enzyme result from
      transcriptional activation of the 'malic' enzyme gene, mediated by binding of the
      peroxisome proliferator activated receptor (PPAR alpha)/retinoid X receptor (RXR
      alpha) heterodimer to a 5'-flanking enhancer of the 'malic' enzyme promoter. The
      enhancer involved is distinct from the thyroid hormone response element of the
      'malic' enzyme promoter and is partly homologous with that which mediates
      transcriptional activation of peroxisomal acyl-CoA oxidase by peroxisome
      proliferators. Hence transcriptional activation of thyroid-hormone-dependent
      liver genes by xenobiotic or endogenous amphipathic carboxylates collectively
      defined as peroxisome proliferators is mediated by a transduction pathway similar
      to that involved in transcriptional activation of peroxisomal beta-oxidative
      genes and distinct from that which mediates thyroid hormone action.

PMID- 8870675
TI  - Molecular cloning and characterization of PTP pi, a novel receptor-like protein
      tyrosine phosphatase.
AB  - Novel cDNAs encoding a receptor-like protein-tyrosine phosphatase (rPTP) have
      been isolated from human breast tumour cells and foetal brain. The predicted
      protein of approximately 160 kDa, called PTP pi, comprises an extracellular
      portion with a MAM (meprin-A5 antigen-PTP mu) domain, an IgG-like domain and four
      fibronectin III-like repeats, a hydrophobic transmembrane domain and an
      intracellular portion consisting of two PTP catalytic units. The predicted amino
      acid sequence shows high identity with those of the two homophilic binding rPTPs,
      PTP mu and PTP kappa. A variant of PTP pi potentially encoding a protein lacking
      three amino acids within the N-terminal tyrosine phosphatase domain has been
      identified. Reverse transcription-PCR has been used to confirm the expression of
      the variant in human foetal brain tissue. Expression analysis has shown that PTP
      pi is expressed in a variety of tissue types. Both forms of the N-terminal
      catalytic domain, the C-terminal catalytic domain and both catalytic domains in
      tandem were expressed in bacteria as fusion proteins. Intrinsic phosphatase
      activity was detected for all protein products with an artificial substrate. The
      fusion protein comprising both domains in tandem was also shown to
      dephosphorylate purified autophosphorylated epidermal growth factor receptor in
      vitro.

PMID- 8870676
TI  - Localization and targeting of isocitrate lyases in Saccharomyces cerevisiae.
AB  - Native isocitrate lyase from castor bean and a C-terminally truncated variant
      were expressed in Saccharomyces cerevisiae under the control of a galactose
      inducible promoter. Both forms of isocitrate lyase were targeted to the yeast
      peroxisomes. They co-fractionated with catalase on sucrose-density-gradient
      centrifugation of a post-nuclear supernatant prepared from cells grown on oleic
      acid plus galactose, but were found in the cytosolic fractions when the cells
      were grown under conditions that repress peroxisome formation. The endogenous S.
      cerevisiae isocitrate lyase was found solely in the cytoplasmic fractions, even
      under growth conditions that induce peroxisome proliferation. This result shows
      that the presence of isocitrate lyase in peroxisomes is not essential for a
      functional glyoxylate cycle. Although the heterologous enzyme was transported to
      peroxisomes it was not enzymically active. Immunocytochemical studies provide
      independent evidence that the plant enzyme is imported into the matrix of yeast
      peroxisomes.

PMID- 8870677
TI  - Alterations in nutritional status regulate acetyl-CoA carboxylase expression in
      avian liver by a transcriptional mechanism.
AB  - Feeding previously starved chicks with a high-carbohydrate, low-fat diet
      stimulates a 9-fold increase in both the rate of synthesis of acetyl-CoA
      carboxylase (ACC) and the abundance of its mRNA in liver. To define the steps
      involved in mediating diet-induced changes in the abundance of ACC mRNA,
      transcriptional activity was measured with the nuclear run-on assay and multiple
      DNA probes specific to the ACC gene. ACC transcription was low in livers of
      starved chicks; feeding them with a high-carbohydrate, low-fat diet induced ACC
      transcription, increasing it 11-fold. An increase in transcription was detectable
      at 1 h, was maximal at 5 h and remained high for 26 h. Feeding previously starved
      chicks with a low-carbohydrate, high-fat diet stimulated a smaller increase (4
      fold) in the abundance of ACC mRNA and the transcription of ACC than feeding with
      a high-carbohydrate, low-fat diet. The half-life of ACC mRNA in liver, as
      estimated from the kinetics of accumulation and decay of ACC mRNA during high
      carbohydrate feeding and starvation, was not changed significantly by dietary
      manipulation. ACC mRNA was expressed at low levels in heart, pectoral muscle,
      kidney and brain. The abundance of ACC mRNA in these tissues was not affected by
      nutritional manipulation. These results demonstrate that nutritional control of
      the abundance of ACC mRNA in the chicken is liver-specific and is mediated
      primarily by changes in the rate of transcription of the ACC gene.

PMID- 8870678
TI  - Conformational changes and the role of metals in the mechanism of type II
      dehydroquinase from Aspergillus nidulans.
AB  - We have investigated the involvement of metal ions and conformational changes in
      the elimination reaction catalysed by type II dehydroquinase from Aspergillus
      nidulans. Mechanistic comparisons between dehydroquinases and aldolases raised
      the possibility that, by analogy with type II aldolases, type II dehydroquinases
      may require bivalent metal ions for activity. This hypothesis was tested by a
      combination of metal analysis, effects of metal chelators and
      denaturation/renaturation experiments, all of which failed to show any evidence
      that type II dehydroquinases are metal-dependent dehydratases. Analysis of native
      and refolded enzyme by electron microscopy showed that the dodecameric type II
      enzyme from A. nidulans adopts a ring-like structure similar to that of glutamine
      synthase, suggesting an arrangement of two hexameric rings stacked on top of one
      another. Evidence for a ligand-induced conformational change came from both
      chemical modification and proteolysis experiments. Inactivation data with the
      arginine-specific reagent phenylglyoxal indicated that, at pH 7.5, two arginine
      residues are modified: one modification displays affinity-labelling kinetics and
      has a 1:1 stoichiometry, while the other displays simple bimolecular kinetics and
      a stoichiometry of 2:1. The labelling at the affinity site is markedly enhanced
      by the addition of ligand, implying that this active-site residue is further
      exposed to modification by phenylglyoxal as a result of a ligand-induced
      conformational change. A combination of proteolysis and electrospray MS
      experiments identified the site of affinity labelling as Arg-19. The highly
      conserved N-terminal region encompassing Arg-19 of type II dehydroquinase was
      found to be particularly susceptible to proteolytic cleavage Limited digestion
      with proteinase K inactivates the enzyme, although the type II oligomeric
      structure is retained, and ligand binding partially protects against this
      inactivation.

PMID- 8870679
TI  - Distinct inhibitory ATP-regulated modulatory domain (ARMi) in membrane guanylate
      cyclases.
AB  - Depending upon the cofactors Mg2+ or Mn2+, ATP stimulates or inhibits the signal
      transduction activities of the natriuretic factor receptor guanylate cyclases,
      ANF-RGC and CNP-RGC: there is stimulation in the presence of Mg2+ and inhibition
      in the presence of Mn2+. A defined core ATP-regulated modulatory (ARM) sequence
      motif within the intracellular 'kinase-like' domain of the cyclases is critical
      for stimulation, but the mechanism of the inhibitory transduction process is not
      known. In addition, ATP inhibits the basal cyclase activity of a rod outer
      segment membrane guanylate cyclase (ROS-GC). The mechanism of this inhibitory
      transduction process is also not known. These issues have been addressed in the
      present investigation through a program of deletion mutagenesis/expression
      studies of the cyclases. The study shows that the ATP-mediated inhibitory
      transduction processes of the natriuretic factor receptor cyclases and of ROS-GC
      are identical. The ATP-regulated inhibitory domain of all these cyclases resides
      within the C-terminal segment of the cyclase. This domain is in a different
      location from the one representing the ATP-stimulatory ARM. The identification of
      the inhibitory domain in the C-terminal segment of the cyclase indicates that
      this segment is composed of two separate domains: one representing a catalytic
      cyclase domain and the other an ATP-regulated inhibitory (ARMi) domain. These
      findings establish a novel ATP-mediated inhibitory transduction mechanism of the
      membrane guanylate cyclases which is distinct from that of its counterpart, the
      stimulatory ATP-mediated hormonal signal transduction mechanism. Thus, they
      define a new paradigm of guanylate cyclase-linked signal transduction pathways.

PMID- 8870680
TI  - Tissue-specific distribution and subcellular distribution of phospholipase D in
      rat: evidence for distinct RhoA- and ADP-ribosylation factor (ARF)-regulated
      isoenzymes.
AB  - Phospholipase D (PLD) is regulated by many factors including the small G
      proteins, RhoA and ADP-ribosylation factor (ARF). The present study examined the
      distribution of RhoA- and ARF-responsive PLD in membranes, microsomes and cytosol
      of rat tissues and in rat liver subcellular fractions. PLD was present in all
      tissue fractions examined and was stimulated by guanosine 5'-[gamma
      thio]triphosphate (GTP[S]), with the highes: specific activities being in lung,
      kidney and spleen. When myristoylated recombinant ARF (mARF) was added with
      GTP[S], the PLD activity was stimulated further, but the addition of RhoA was
      without effect. However, in extracts from crude membranes both mARF and RhoA
      enhanced the stimulation by GTP[S], with high specific activities of PLD being
      observed in all tissues except muscle. The response to mARF was usually greater
      than to RhoA, and the responses were additive, except for liver, which showed
      synergism. When the PLD activity of subcellular fractions of liver was examined,
      GTP[S] caused increases in all fractions except microsomes and mitochondria,
      which exhibited low activity. All fractions except mitochondria showed responses
      to RhoA and mARF, with the response to RhoA being greater in plasma membranes and
      that to mARF being greater in Golgi and nuclei. Western blotting showed that RhoA
      was located mainly in the cytosol and plasma membranes, whereas ARF was
      principally in the cytosol. These findings demonstrate the widespread occurrence
      of significant activity of both Rho- and ARF-responsive forms of PLD in membranes
      from all tissues except muscle, and the presence of both forms in liver
      subcellular fractions except mitochondria. The large variations in the relative
      responses of PLD to Rho and ARF observed in different tissues and fractions
      support the existence of different isoforms of the enzyme.

PMID- 8870681
TI  - The CDC2-related kinase PITALRE is the catalytic subunit of active multimeric
      protein complexes.
AB  - PITALRE is a human protein kinase identified by means of its partial sequence
      identity to the cell division cycle regulatory kinase CDC2. Immunopurified
      PITALRE protein complexes exhibit an in vitro kinase activity that phosphorylates
      the retinoblastoma protein, suggesting that PITALRE catalyses this
      phosphorylation reaction. However, the presence of other kinases in the
      immunopurified complex could not be ruled out. In the present work, an inactive
      mutant of the PITALRE kinase has been used to demonstrate that PITALRE is the
      catalytic subunit responsible for the PITALRE-complex-associated kinase activity,
      Ectopic overexpression of PITALRE did not increase the total PITALRE kinase
      activity in the cell, suggesting that PITALRE is regulated by limiting cellular
      factor(s). Characterization of the PITALRE-containing protein complexes indicated
      that most of the cellular PITALRE protein exists as a subunit in at least two
      different active multimeric complexes. Although monomeric PITALRE is also active
      in vitro, PITALRE present in multimeric complexes exhibits several-fold higher
      activity than monomeric PITALRE. In addition, overexpression of PITALRE
      demonstrated the existence of two new associated proteins of approx. 48 and 98
      kDa. Altogether these results suggest that, in contrast to the situation with
      cyclin-dependent kinases, monomeric PITALRE is active, and that association with
      other proteins modulates its activity and/or its ability to recognize substrates
      in vivo.

PMID- 8870682
TI  - Nitric oxide-induced apoptosis: p53-dependent and p53-independent signalling
      pathways.
AB  - Nitric oxide (NO) generation initiates apoptotic cell death in different
      experimental systems. In RAW 264.7 macrophages the appearance of typical
      apoptotic markers is linked to inducible NO synthase induction. Mechanistically,
      accumulation of tumour suppressor p53 precedes apoptotic DNA fragmentation. With
      the use of S-nitroglutathione (GSNO) we correlated a dose-dependent p53 up
      regulation to DNA fragmentation measured after 4 h and 8 h, respectively. Our
      studies revealed a linear correlation between the potency of five different NO
      donors with respect to apoptosis induction and p53 accumulation. Furthermore, we
      probed for NO-induced apoptosis after stable transfection of RAW 264.7
      macrophages with plasmids encoding p53 antisense RNA. Clones with down-regulated
      p53 levels in response to GSNO exhibited a marked reduction in DNA fragmentation.
      Expression of the inducible NO synthase in response to lipopolysaccharide and
      interferon-gamma caused apoptosis in RAW 264.7 macrophages and neomycin-vector
      controls within 24 h. In contrast, p53 antisense RNA-expressing clones appeared
      highly resistant towards endogenous NO, although inducible NO synthase induction
      with concomitant nitrite production remained unchanged. For RAW 264.7 macrophages
      our results established a functional role of the tumour suppressor p53 during NO
      induced apoptotic cell death. However, p53 antisense experiments and the use of
      the p53-negative cell line U937 substantiated p53-independent signalling pathways
      operative during NO-mediated apoptosis.

PMID- 8870683
TI  - Transfection of human topoisomerase II alpha into etoposide-resistant cells:
      transient increase in sensitivity followed by down-regulation of the endogenous
      gene.
AB  - We have investigated the possibility of overcoming the resistance of human brain
      tumour cells (HBT20) to etoposide by transferring the normal human topoisomerase
      II alpha (H-topo II) gene into these cells. H-topo II in a mammalian expression
      vector containing a glucocorticoid-inducible mouse mammary tumour virus (MMTV)
      promoter was transfected into etoposide-resistant HBT20 cells (HBT20-hTOP2MAM).
      HBT20 cells transfected with pMAMneo vector alone served as control cells (HBT20
      MAM). These were stable transfections. Following a 2 h dexamethasone treatment, H
      topo II mRNA expression, protein production, etoposide-induced DNA-protein
      complex formation and sensitivity to etoposide were increased in HBT20-hTOP2MAM
      cells compared with control HBT20-MAM cells and with HBT20-hTOP2MAM cells not
      treated with dexamethasone. However, mRNA and protein levels and cell sensitivity
      returned to baseline when incubation with dexamethasone was continued for 24 h.
      This decrease from the 2 h values could not be explained by a loss of the MMTV
      promoter response to dexamethasone. (H-topo II alpha promoter)-(chloramphenicol
      acetyltransferase) constructs containing regions -559-0 and -2400-0 were
      significantly down-regulated in HBT20-hTOP2MAM cells treated for 24 h with
      dexamethasone compared with dexamethasone-treated control cells. H-topo II mRNA
      stability after 24 h of dexamethasone treatment was not altered compared with
      that in control cells. Our data indicate that the exogenously produced H-topo II
      may have a negative-feedback effect on the endogenous topoisomerase II promoter,
      causing down-regulation of the endogenous gene.

PMID- 8870684
TI  - Mutagenesis of the active site of the human Theta-class glutathione transferase
      GSTT2-2: catalysis with different substrates involves different residues.
AB  - The role of serine-11 in the catalytic mechanism of recombinant human GSTT2-2 was
      examined by site-directed mutagenesis. Amino acid sequence comparison of the
      Theta-class isoenzymes has identified a conserved serine residue in the N
      terminal domain [Wilce, Board, Feil and Parker (1995) EMBO J. 14, 2133-2143].
      This conserved serine has been implicated in the activation of the enzyme-bound
      glutathione [Board, Coggan and Parker (1995) Biochem. J. 311, 247-250]. Mutating
      the equivalent serine (residue 11) of GSTT2-2 to Ala, Thr or Tyr abolished the
      catalytic properties of GSTT2-2 with cumene hydroperoxide and ethacrynic acid as
      second substrate. However, with l-menaphthyl sulphate (MSu) as the second
      substrate, the specific activity of the S11A mutant was doubled, while the S11T
      mutant retained half the wild-type activity and the S11Y mutant was inactive. The
      role of Ser-11 in catalysis seems to vary with different second substrates. In
      the substitution reaction with MSu, GSTT2-2 activity appears to depend on the
      size of the Ser-11 replacement rather than the presence of a side-chain hydroxy
      group. In addition, the reaction rate appears to be a function of pH, and there
      is no non-enzymic reaction even at high pH. We demonstrated that a reaction
      between MSu and an alternative thiol such as L-cysteine or 2-mercaptoethanol can
      take place in the presence of S-methylglutathione and GSTT2-2. We propose that
      the catalytic activity of GSTT2-2 with MSu is preceded by a conformational or
      charge modification to the enzyme upon the binding of glutathione or S
      methylglutathione. This is followed by the binding of MSu and the subsequent
      removal of the sulphate group, giving rise to the carbonium ion of l
      methylnaphthelene as the electrophile that reacts with the nucleophilic species.
      The reaction mechanism of GSTT2-2 with MSu may represent a novel function of
      GSTT2-2 as a glutathione-dependent sulphatase.

PMID- 8870685
TI  - An increase in cytosolic Ca2+ delays cAMP oscillations in Dictyostelium cells.
AB  - We have shown that calmidazolium (R24571) causes a transient increase in the
      cytosolic free Ca2+ concentration ([Ca2+]i) in Dictyostelium discoideum
      [Schlatterer and Schaloske (1996) Biochem. J. 313, 661-667]. Here we have used
      R24571 to artifically increase [Ca2+]i during light-scattering oscillations and
      have found that, depending on the time of addition during the oscillatory cycle,
      R24571 suppressed cAMP synthesis and delayed the next spike for several minutes.
      Addition of Ca2+ to the medium, which also elevates [Ca2+]i, induced phase delays
      and resulted in a similar phase response curve as R24571. The magnitude of the
      phase delay was correlated with the point during the oscillatory cycle at which
      Ca2+ was added, indicating that an artificial increase in [Ca2+]i also resets the
      phase of the intrinsic oscillator.

PMID- 8870686
TI  - Modulation of human neutrophil chemotaxis by the endothelin-B receptor agonist
      sarafotoxin S6c.
AB  - At low concentrations (4 x 10(-9) M) sarafotoxin S6c, a selective agonist of the
      ETB receptor, caused a slight but significant chemotactic enhancement of
      neutrophil migration. In contrast with stimulation by endothelins, stimulation of
      migration by sarafotoxin was only mediated by the ETB receptor because BQ123, a
      selective antagonist of the ETA receptor, had no effect on the enhancement. At
      higher concentrations (10(-8) M and higher) sarafotoxin inhibited neutrophil
      migration stimulated by chemotactic activators. It thus appears that the ETB
      receptor mediates the inhibition of migration by high concentrations of
      sarafotoxin. The degree of inhibition by sarafotoxin was dependent on the type of
      activator; especially IL-8 activated migration was strongly inhibited.
      Extracellular calcium had little effect on stimulation or inhibition by
      sarafotoxin, in contrast with endothelins. In a very small concentration range (4
      x 10(-8) M) sarafotoxin caused an increase of cytoplasmic free calcium; higher
      concentrations of sarafotoxin had no effect on cytoplasmic calcium, nor did they
      affect calcium changes caused by fMet-Leu-Phe (fMLP). IRL1038, a selective
      antagonist of the ETB receptor, equally gave a small potentiation at low
      concentrations, and inhibited agonist-activated chemotaxis at higher
      concentrations, suggesting that occupation of the ETB receptor by either agonist
      or antagonist results in a modulation of migration.

PMID- 8870687
TI  - Inter-individual variability in the oxidation of 1,2-dibromoethane: use of
      heterologously expressed human cytochrome P450 and human liver microsomes.
AB  - 1,2-Dibromoethane (1,2-DBE) is mainly used as an additive in leaded gasoline and
      as a soil fumigant and it is a suspected carcinogen in humans. In this study, the
      oxidative bioactivation of 1,2-DBE to 2-bromoacetaldehyde (2-BA) was studied
      using heterologously expressed human cytochrome P450 (P450) isoenzymes and human
      liver microsomes. Out of ten heterologously expressed human P450 isoenzymes
      (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1, CYP2C8, CYP2C9, CYP2C18, CYP3A4 and
      CYP3A5), only human CYP2A6, CYP2B6 and CYP2E1 metabolized 1,2-DBE, albeit with
      strongly differing catalytic efficiencies. The apparent Km and Vmax values were
      3.3 mM and 0.17 pmol/min per pmol P450 for CYP2A6, 9.7 mM and 3.18 pmol/min per
      pmol P450 for CYP2B6 and 42 microM and 1.3 pmol/min per pmol P450 for CYP2E1,
      respectively. In all of 21 human liver samples studied, 1,2-DBE was oxidized with
      activities ranging from 22.2 to 1027.6 pmol/min per mg protein, thus showing a 46
      fold inter-individual variability. The kinetics of the oxidative metabolism of
      1,2-DBE to 2-BA in human liver microsomes were linear, indicating the involvement
      of primarily one single P450 isoenzyme. There was a tendency towards a positive
      correlation between the oxidative metabolism of 1,2-DBE in the human liver
      microsomes and the 6-hydroxylation of chlorzoxazone, a selective substrate for
      CYP2E1. Furthermore, the oxidative metabolism of 1,2-DBE was inhibited by the
      specific CYP2E1 inhibitors disulfiram (DS) and diethyldithiocarbamate (DDC). In
      contrast, a poor correlation was found between the immunochemically quantified
      amount of CYP2E1 and the microsomal chlorzoxazone 6-hydroxylation or the 1,2-DBE
      oxidation. The results indicate that CYP2E1 is probably the major P450 isoenzyme
      involved in the oxidative hepatic metabolism of 1,2-DBE in humans. The inter
      individual variability in the oxidative bioactivation of 1,2-DBE in humans,
      largely due to inter-individual variability in the catalytic activity of hepatic
      CYP2E1, may have important consequences for the risk assessment for human
      exposure to 1,2-DBE.

PMID- 8870688
TI  - Adducts to N-terminal valines in hemoglobin from butadiene metabolites.
AB  - In order to identify a hemoglobin adduct useful for monitoring of doses of
      butadiene metabolites, particularly the strongly genotoxic, bifunctional
      diepoxybutane (DEB), the reaction of DEB with valinamide, a relevant model of
      globin N-termini, was studied. A preliminary kinetic analysis showed that the
      primary reaction product of DEB with valine-N gives, as was expected, rise to a
      ring-closed pyrrolidine-structured compound, N,N-(2,3-dihydroxybuta-1,4
      diyl)valine (PYRV), in a reaction which is fast when compared to hydrolysis of
      the second oxirane ring with formation of N-(2,3,4-trihydroxybutyl)valine (THBV).
      The ring closure is also fast when compared to the rate of formation of a cross
      linked divaline product. PYRV can therefore be used as a specific marker of in
      vivo doses of DEB whereas THBV may be applied for the dosimetry of the metabolite
      (1,2-dihydroxyethyl)oxirane. The latter is formed by half-hydrolysis of DEB or
      oxygenation of 1,2-dihydroxy-3-butene. The N-alkyl Edman method, used for
      specific cleavage and gas chromatographic/mass spectrometric (GC/MS)
      determination of adducts to N-terminal valine in hemoglobin, could be used for
      measurement of THBV, as shown in alkylation experiments with blood. However, the
      adduct specific for DEB, PYRV, requires-due to its tertiary amine structure-other
      techniques. The reaction products were identified by GC/MS, PYRV by 13C and 1H
      NMR, and THBV because of its formation by reduction of the Schiff bases of
      threose and erythrose with hemoglobin.

PMID- 8870689
TI  - Cytochrome P450 enzymes involved in the enhancement of propranolol N
      desisopropylation after repeated administration of propranolol in rats.
AB  - Repeated oral administration of propranolol (PL, 100 mg/kg daily, for 5, 10 and
      15 days) to male Wistar rats increased PL N-desisopropylase and decreased PL 4-,5
      and 7-hydroxylase activities in liver microsomes. The increase was highest at
      the 10 day time point whereas the decrease was relatively constant over the 15
      day treatment period. There were no significant changes in the total content of
      cytochromes P450 (P450) or cytochrome b5 or in NADPH-cytochrome c reductase
      activity during the PI, treatment. The enhanced N-desisopropylase activities were
      markedly inhibited by alpha-naphthoflavone (a P450-1A1/2 inhibitor), and
      moderately by triacetyloleandomycin (a P450-3A1/2 inhibitor) and
      diethyldithiocarbamate (a P450-2E1 inhibitor). Phenacetin O-deethylase activity,
      an index of P450-1A2, was significantly increased on day 5, 10 and 15 of the
      treatment, whereas p-nitrophenol hydroxylase activity was elevated on day 10
      only. The PL N-desisopropylation showed a strong and significant correlation with
      phenacetin O-deethylation, and a weaker but significant correlation with p
      nitrophenol hydroxylation. Immunoblot analysis revealed that a protein band
      corresponding to P450-1A2 was increased by PL pretreatment, and protein band
      corresponding to P450-3A tended to be increased slightly, but other protein band
      corresponding to the subfamily of P450-2B, -2C, or -2E was not changed.
      Pretreatment of rats with P450 inducers (beta-naphthoflavone, phenobarbital,
      acetone and dexamethasone) increased PL N-dealkylase activity in liver
      microsomes. Furthermore, antibodies raised against P450-1A and -3A enzymes
      suppressed PL N-desisopropylation in a concentration-dependent manner, but P450
      2E antibody did not. Reconstitution studies showed that P450-1A1, -1A2, -2E1 and 
      3A2 exhibited catalytic activities for PL N-dealkylation. These results suggest
      that P450-1A2 is a major PL N-desisopropylase in the PL-treated rats, and P450-3A
      related enzyme(s) and P450-2E1 as a moderate or minor enzyme are also involved in
      PL N-dealkylation in native and PL-treated rats.

PMID- 8870690
TI  - Intrastructural help in diversification of humoral autoimmune responses.

PMID- 8870691
TI  - Evidence for a selected humoral immune response encoded by VH4 family genes in
      the synovial membrane of a patient with rheumatoid arthritis (RA).
AB  - The analysis of rearranged antibody-encoding genes from B cell foci in rheumatoid
      synovial tissue has characterized these cells as highly mutated memory B cells
      with a high proportion of members of the VH4 family. In order to characterize
      further the VH4 response in one patient, B cell-rich areas from different
      sections of synovial membrane (SM) were identified by CD20 staining, isolated by
      microdissection and pooled, in order to analyse highly enriched B cells without
      selection by in vitro culture procedures. From DNA of about 5 x 10(3) B cells
      rearranged VH genes were amplified by polymerase chain reaction (PCR) and cloned.
      Sequencing of 11 clones containing rearranged VH4 gene products revealed that
      seven were potentially functional, and all were mutated with 84-96% homology to
      known germ-line (gl) genes and VH4 gl genes amplified from the patient's genomic
      DNA. Analysis of the complementarity determining region (CDR) 3 revealed that two
      products represented members of one B cell clone which differed by five
      nucleotide changes. Three of the five mutations encoded amino acid replacements
      in CDRs indicating antigen-driven expansion of one specific clone. Additional
      analyses of 25 members of three B cell clones from isolated aggregates showing
      intraclonal diversity in one of three clones provided further evidence that
      antigen selection takes place in the SM. Overall, the pattern of mutations and
      the replacement to silent (R:S) ratios were diverse, with six products indicating
      antigen selection by their high R:S ratios in CDRs. Although DNA analysis does
      not allow a characterization of antibody specificities, we can conclude from our
      analysis does not allow a characterization of antibody specificities, we can
      conclude from our analysis of antibody-encoding genes that selection by antigen
      and expansion of specific clones occur in the SM against the background of
      polyclonal activation.

PMID- 8870692
TI  - Blood monocyte activation in rheumatoid arthritis: increased monocyte
      adhesiveness, integrin expression, and cytokine release.
AB  - Infiltration of the synovium by mononuclear cells, namely lymphocytes and
      monocytes, is one of the main features of rheumatoid arthritis (RA) and is
      considered to be responsible for the development of the disease. In this study in
      31 consecutive patients with RA, we investigated whether peripheral blood
      monocytes exhibited markers of cellular activation related to cell migration.
      Using flow cytometry with the respective specific antibodies, we studied the
      expression of integrins CD11a, CD11b, CD11c, CD49d (VLA-4), and CD49e (VLA-5) on
      monocytes from patients with RA and from normal (N) subjects. IL-1 beta, IL-6,
      and tumour necrosis factor-alpha (TNF-alpha) production by cultured monocytes was
      measured by immunoassay. Adhesiveness of monocytes was studied on various
      surfaces (plastic, human fibronectin, gelatin-coated plasma, subendothelial
      matrix) and on cultured endothelial cells under basal conditions or after
      stimulation by IL-1 beta. An increased number of CD14+ monocytes (Mo) from RA
      patients expressed the CD11b molecule (RA Mo = 90.3%, N Mo = 83.4%, P < 0.005).
      The expression of CD11b on CD14+ monocytes was significantly increased in RA
      patients (median fluorescence intensity (FI): RA Mo = 145 (range 80-466) units;
      normal Mo = 95 (range 24-164) units; P < 0.003). Production of extracellular IL-1
      beta and IL-6 by RA monocytes was significantly enhanced compared with monocytes
      from normal subjects (IL-1 beta: RA = 2.65 +/- 0.91 ng/ml versus N = 1.35 +/-
      0.85 pg/ml, P < 0.05; IL-6: RA = 4.83 +/- 0.90 ng/ml versus N = 2.40 +/- 0.95
      ng/ml, P < 0.05). Compared with normal monocytes, RA monocytes exhibited
      increased adhesion to the various surfaces studied (plastic, P < 0.01;
      fibronectin, P < 0.01; and gelatin-coated normal or RA plasma, P < 0.01) as well
      as to unstimulated (P < 0.01) and IL-1 beta-stimulated endothelial cells (IL-1
      beta for 4 h, P < 0.05; IL-1 beta for 24h, P < 0.05). In our study, blood
      monocytes from RA patients exhibited features of activation related to cell
      adhesion.

PMID- 8870693
TI  - Mononuclear cell retention in rheumatoid synovial tissue engrafted in severe
      combined immunodeficient (SCID) mice is up-regulated by tumour necrosis factor
      alpha (TNF-alpha) and mediated through intercellular adhesion molecule-1 (ICAM
      1).
AB  - The aim of this study was to assess regulation of mononuclear cell (MNC) traffic
      to human synovial tissue by TNF-alpha and IL-1 and the involvement of ICAM-1 in
      MNC retention in rheumatoid synovial tissue. Human rheumatoid arthritis synovium
      was engrafted subcutaneously in 6-8 week-old SCID/CB17 mice. Three weeks later,
      we injected 20 x 10(6) human peripheral blood mononuclear cells (PBMC) previously
      labelled with 111indium intraperitoneally into mice containing control or
      cytokine-injected grafts. Total body scintigraphy was performed 72 h
      postinjection. The graft was removed and immunochemical analysis carried out to
      assess ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin
      expression. In some experiments, mice were treated intravenously with 500
      micrograms MoAb anti-ICAM-1 (BIRR-1) or an isotype-matched control MoAb before
      introduction of MNC. TNF-alpha, but not IL-1 alpha, enhanced MNC retention in the
      rheumatoid synovial graft 72 h post-injection (graft activity 989 +/- 1227 ct/min
      per 200 pixels or 3.36 +/- 4.16% of initial injected activity versus 411 +/- 157
      ct/min per 200 pixels or 1.13 +/- 0.45% in controls; P < 0.03). TNF-alpha
      enhanced ICAM-1 expression by synovial cells and endothelial cells, whereas VCAM
      1 or E-selectin expression was not enhanced on either cell type. After MoAb
      treatment of ICAM-1, synovial lymphocyte recruitment of TNF-alpha-treated mice
      decreased significantly to levels below that of control mice (160 +/- 97 ct/min
      per 200 pixels, 0.54 +/- 0.33%; P < 0.01). Mononuclear cell retention in
      rheumatoid synovial tissue engrafted into SCID mice was up-regulated by TNF-alpha
      and blocked by MoAb to ICAM-1. These results suggest that ICAM-1 is involved in
      mononuclear cell retention in rheumatoid synovium.

PMID- 8870694
TI  - Role of macrophages in the development of arteritis in MRL strains of mice with a
      deficit in Fas-mediated apoptosis.
AB  - The lpr and gld genes have been shown to encode the Fas antigen deletion mutant
      and the Fas ligand (FasL) mutant, respectively. An MRL strain of mice bearing the
      gld gene was observed to spontaneously develop granulomatous arteritis, similar
      to that in mice bearing the lpr gene, indicating that arteritis in this strain is
      due to an inefficient Fas-FasL interaction resulting in an incapacity for Fas
      mediated apoptosis. The arterial lesions in both strains were characterized by a
      remarkable perivascular accumulation of activated macrophages bearing Mac-2
      antigen, following the infiltration of CD4+ cells, and this resulted in the
      destruction of the arterial wall. Almost all of these infiltrating cells were Fas
      positive, as determined in MRL/gld mice. Macrophage colony-stimulating factor (M
      CSF), which is present at increased levels in MRL/lpr mice, but not in MRL/Mp-
      +/+ (MRL/+) mice, induced the expression of Mac-2 antigen and Fas antigen on
      spleen adherent cells of MRL/+ mice. Moreover, continuous infusion of M-CSF into
      the peritoneal cavity of subcutis of MRL/+ mice induced the release of oxygen
      radicals of peritoneal macrophages or granuloma formation associated with the
      massive accumulation of Mac-2+ cells, respectively. These findings suggest that
      macrophages in these mice, which may be activated by M-CSF and may avoid Fas
      mediated apoptosis, play a critical role as effector cells in the destruction of
      arterial wall.

PMID- 8870695
TI  - Site-directed serology of HIV-1 subtype B infection: relation between virus
      specific antibody levels and disease progression.
AB  - Activated T helper (Th) cell-dependent (TD) antibody responses were determined
      over an 8-10 year period in 28 patients infected with HIV-1 subtype B. Twelve
      patients remain asymptomatic with normal CD4+ cell counts for 101-114 months.
      These individuals were defined as long-term asymptomatic (LTA). Sixteen patients
      progressed to severe immunodeficiency within 58-120 months. In samples derived
      close to the diagnosis of HIV-1, CD4+ cell counts were higher among the LTAs (P <
      0.01). Antibody production driven by activated Th cells was determined using
      peptides corresponding to HIV-1 V3US/Eur, gp41, and the hepatitis C virus (HCV)
      core proteins. The less Th cell-dependent B cell antibody response was
      represented by measles virus immunity. Close to HIV-1 diagnosis, variable third
      (V3), gp41, HCV core, and measles antibody titres were at similar levels among
      the LTAs and the progressors. With time the LTAs displayed unchanged levels of V3
      and gp41 antibodies, and slightly decreasing levels of HCV core antibodies (P <
      0.05). In contrast, the progressors showed a decrease in all these antibody
      responses (P < 0.05, for all). In both groups, the levels of measles antibody
      remained stable. Our data show that no significant change of the antibody
      responses of LTAs is seen, even after 101-114 months of known HIV-1 infection.
      Furthermore, the marked decrease of TD antibody production in the progressors
      suggests that activated Th cells may be excellent targets for HIV-1 infection.

PMID- 8870696
TI  - Inhibition of natural killer (NK) cell activity against varicella-zoster virus
      (VZV)-infected fibroblasts and lymphocyte activation in response to VZV antigen
      by nitric oxide-releasing agents.
AB  - The addition of nitric oxide (NO)-releasing agents, S-nitroso-N-acetyl-DL
      penicillamine (SNAP), 1-hydroxy-2-oxo-2,3-bis(2-aminoethyl)-1-triazene (NOC18),
      30{(+/-)-(E)-ethyl-2'-[(E)-hydroxyimino]-5-nitro-3-hexenecarbam oyl} -pyridine
      (NOR4) significantly inhibited NK cell activity against VZV-infected cells, while
      antibody-dependent cell-mediated cytotoxicity (ADCC) against VZV-infected cells
      was unaffected. Interferon-alpha (IFN-alpha) production by non-adherent
      peripheral blood mononuclear cells (NPBMC) cultured with VZV-infected cells was
      decreased by the addition of NO-releasing agents. Lymphocyte proliferation and
      the expression IL-2 receptor (CD25) in response to VZV antigen were also
      inhibited by the addition of NO-releasing agents. These results suggest that the
      production of NO by an inflammatory process may lead to inhibition of NK cell-
      and T cell-mediated immunity to VZV infection.

PMID- 8870697
TI  - Specific immunoglobulin measurements related to exposure and resistance to
      Schistosoma mansoni infection in Sudanese canal cleaners.
AB  - The present work comprises a longitudinal study of Schistosoma mansoni infection
      in occupationally hyper-exposed canal cleaners in the Sudan and the influence of
      chemotherapy on humoral immune parameters. The study groups included chronically
      infected canal cleaners (n = 19), newly recruited canal cleaners (n = 17),
      normally exposed adults (n = 31), school children (n = 46) and Sudanese negative
      controls (n = 48). Previous studies of the same canal cleaners have demonstrated
      that chronically infected canal cleaners were more resistant to reinfection than
      newly recruited canal cleaners. ELISA was used to detect specific IgE and IgG
      subclasses in response to whole worm antigen (WWH) and soluble egg antigen (SEA)
      before and 3 months after praziquantel treatment in the groups of canal cleaners
      and before and 1 year after treatment in normally exposed adults. When intensity
      of infection was correlated with IgE antibody response, the resistant group of
      canal cleaners (those who stopped passing ova after treatment) showed a
      significant positive correlation between intensity of infection and specific IgE
      to WWH (Spearman's correlation coefficient = 0.49, P < 0.05) compared with a
      highly significant negative correlation in the susceptible group (acquired new
      infection after treatment, Spearman's correlation coefficient = -0.94, P < 0.01).
      Normally exposed adults and school children had significantly less specific IgE
      to WWH than canal cleaners, while chronically infected canal cleaners had
      significantly higher levels of specific IgG1 to WWH than newly recruited canal
      cleaners and school children, and significantly higher levels of specific IgG4 to
      WWH than school children. There was a significant increase in specific IgG1 and
      IgG4 to WWH, 3 months after treatment, in newly recruited canal cleaners and a
      significant decrease, 1 year after treatment, in normally exposed adults. None of
      the groups studied after treatment showed a significant change in their specific
      IgE to WWH. Normally exposed adults had significantly lower levels of specific
      IgE to SEA than newly recruited canal cleaners, and significantly lower levels of
      specific IgG1 to SEA than other infected groups. Both newly recruited canal
      cleaners and school children had significantly higher levels of specific IgG2 to
      SEA than persons in other groups. Only small differences between groups were
      observed with regard to specific IgG3 and IgM to SEA. Specific IgG4 to WWH and
      SEA showed different patterns after treatment between the resistant and
      susceptible groups of canal cleaners. The resistant group maintained the same
      level of IgG4 to WWH after treatment compared with a significant increase in the
      susceptible group. On the other hand, levels of specific IgG4 to SEA showed a
      highly significant decrease after treatment in the resistant group. In contrast,
      the same antibody subclass increased after treatment in the susceptible group.
      Generally, results show an association between IgE and IgG1 responses to WWH and
      resistance to reinfection. In contrast, an association was observed between IgG2
      and IgM responses to SEA and susceptibility to reinfection.

PMID- 8870698
TI  - Lung granulomatous response induced by infection with the intestinal nematode
      Nippostrongylus brasiliensis is suppressed in mast cell-deficient Ws/Ws rats.
AB  - Certain nematode infections induce eosinophil infiltration and granulomatous
      responses in the lungs. To examine the role of mast cells in the development of
      lung lesions, normal +/+ and genetically mast cell-deficient Ws/Ws rats were
      infected with the nematode Nippostrongylus brasiliensis. In +/+ rats, numbers of
      eosinophils in bronchoalveolar lavage fluid (BALF) increased significantly 3-7
      days after infection, and granulomatous responses composed of histiocytes/
      macrophages and multinucleate giant cells were triggered in the lungs 3-14 days
      after infection. Challenge infection, which was carried out on day 28 after
      primary infection, induced much higher levels of granulomatous response than
      after primary infection, suggesting that the response is mediated at least in
      part by an immunological mechanism. In Ws/Ws rats, both the eosinophil percentage
      in BALF and the size of the granulomas in the lungs were significantly smaller
      than in +/+ rats after primary as well as after challenge infection. The amount
      of rat mast cell protease (RMCP) II in +/+ rat BALF was increased 1 day after
      primary infection and more significantly after challenge infection, suggesting
      that lung mucosal mast cells were activated more markedly after the challenge
      infection. In Ws/Ws rats, RMCP II was undetectable throughout the observation
      period. The time course of nematode migration in the lungs did not differ in +/+
      and Ws/Ws rats. These results suggest that mast cell activation might be relevant
      to eosinophil infiltration and granulomatous response in the lungs, although the
      responses do not affect lung migration of the nematode.

PMID- 8870699
TI  - Diminished interferon-gamma (IFN-gamma) production by bacterial antigen-specific
      T cells in atopic patients.
AB  - In this study, we established and studied cytokine production of T cell lines
      (TCL) specific to either a purified protein derivative of Mycobacterium
      tuberculosis (PPD) or Dermatophagoides farinae (Df) from atopic patients and non
      atopic healthy subjects. IFN-gamma was detected in the culture supernatants of
      all of 36 PPD-specific TCL established from healthy controls, whereas only 24 of
      38 PPD-specific TCL from patients produced IFN-gamma. Furthermore, the amounts of
      IFN-gamma produced by PPD-specific TCL from patients were significantly lower
      than those from healthy controls. No IL-4 was detected in any PPD-specific TCL
      from either healthy controls or atopic patients. The amounts of IL-4 production
      from Df-specific TCL from atopic patients were much higher than from healthy
      controls, while few TCL produced IFN-gamma. These results suggest that the
      skewing to the Th2-type T cell response in atopic patients is a response not only
      to allergens, but also to bacterial antigens, compared with non-atopic subjects.
      Activation of PPD-specific TCL from patients with calcium ionophore A23187 plus
      phorbol myristate acetate resulted in much higher IFN-gamma production than in
      TCL established from healthy controls, indicating that the low production of IFN
      gamma by PPD-specific T cells from atopic patients is not due to an intrinsic T
      cell defect but to some regulatory mechanisms.

PMID- 8870700
TI  - Spontaneous CD30 mRNA expression in peripheral blood mononuclear cells from
      atopic patients with high IgE serum levels.
AB  - CD30 is a surface molecule which can be expressed by normal B and T lymphocytes.
      Our study focused on the CD30 expression and release compared with IL-4
      expression as well as CD23-alpha/beta in peripheral blood mononuclear cells
      (PBMC) from atopic subjects and controls. Data showed a lack of CD30 mRNA
      expression in the PBMC of control subjects, while it was significantly expressed
      in those of 6/11 atopic patients. No substantial amounts of spontaneous soluble
      CD30 (sCD30) could be detected by ELISA in both atopic and control groups.
      Interestingly, CD30 mRNA expression in PBMC of allergic patients was positively
      correlated with IgE serum levels (r = 0.79, P = 0.003). Studies on purified B
      cells showed that CD30 was expressed mainly in CD19+B cells of allergic patients.
      These data suggest highly a potential functional significance of the CD30
      molecule in IgE response during allergic diseases.

PMID- 8870701
TI  - Elevation of serum soluble tumour necrosis factor (TNF) receptor and IL-1
      receptor antagonist levels in bronchial asthma.
AB  - The specific inhibitor for TNF-alpha activity, soluble form of the 55-kD TNF
      receptor (sTNF-RI) and soluble form of the 75-kD receptor (sTNF-RII), and the
      specific inhibitor for IL-1 activity, IL-1 receptor antagonist (IL-1Ra), have
      been identified. It has been shown that the levels of these inhibitors are
      elevated in plasma/serum and biological fluids in several diseases, and the
      protective and inhibitory effect of these inhibitors exist in several
      inflammatory diseases. In the present study, we measured serum levels of sTNF-RI,
      STNF-RII and IL-1Ra by ELISA in 36 patients with bronchial asthma (16 atopic and
      20 non-atopic) during asthma attacks and in stable conditions in order to assess
      the state of these inhibitors in allergic inflammation. The levels of sTNF-RI,
      sTNF-RII and IL-1Ra in sera obtained during bronchial asthma attacks were higher
      than those in sera obtained in stable conditions. These findings were obtained
      regardless of atopic status. These results suggest that higher levels of serum
      sTNF-RI, sTNF-RII and IL-1Ra may reflect up-regulation of TNF-R expression and IL
      1Ra production in allergic inflammation, and sTNF-RI, sTNF-RII and IL-1Ra may
      contribute to regulating TNF-alpha- and IL-1-mediated production and development
      of allergic inflammation.

PMID- 8870702
TI  - Epitope analysis of the Goodpasture antigen using a resonant mirror biosensor.
AB  - We have used a new technique for studying molecular interactions-a resonant
      mirror biosensor-to identify B cell epitopes within the Goodpasture antigen,
      which has recently been identified as the non-collagenous domain of the alpha 3
      chain of type IV collagen (alpha 3(IV)NC1). Recombinant antigen (r-alpha 3) was
      immobilized onto the sensing surface of a sample cuvette, and the binding of
      patients' autoantibodies or a MoAb to the Goodpasture antigen was followed in
      real time. All patients' sera bound r-alpha 3 in this system, while control sera
      did not bind. A MoAb inhibited the binding of all patients' autoantibodies to r
      alpha 3, from 27% to 90% (mean inhibition 60%), and patients' sera cross
      inhibited the binding of each other to the antigen. Binding was inhibited by pre
      incubation of autoantibody with both native sheep alpha 3(IV)NC1 and purified
      human alpha 3(IV)NC1 monomers. Inhibition experiments using soluble overlapping
      peptides from human alpha 3(IV)NC1 identified putative B cell epitopes. These
      results suggest that there is a major immunodominant epitope on the Goodpasture
      antigen, and that there is very limited heterogeneity in the autoantibody
      response in Goodpasture's disease. The resonant mirror biosensor can be
      successfully used to monitor antibody-antigen binding using polyclonal sera, and
      to map epitopes on autoantigens.

PMID- 8870703
TI  - Thy-1 molecule associates with protein tyrosine kinase(s) in rat mesangial cells.
AB  - Glycophosphatidylinositol (GPI)-linked Thy-1 molecules, well known cell surface
      markers of murine T cells, are present on the glomerular mesangial cells of the
      rat kidney. The administration of anti-Thy-1.1 MoAbs 1-22-3 and OX-7 to rats
      induces severe and mild complement-dependent mesangial proliferative
      glomerulonephritis, respectively. In order to determine whether protein-tyrosine
      kinase (PTK) activity is associated with Thy-1 molecules on rat mesangial cell
      surface, we performed an immune complex kinase assay, using anti-Thy-1 MoAbs 1-22
      3 and OX-7, followed by reimmunoprecipitation with anti-phosphotyrosine, anti
      fyn, anti-lck and anti-lyn antibodies. Physical association of PTK, p59fyn and
      p56/53lyn with Thy-1 molecules was demonstrated in cultured rat mesangial cells.
      The activities of these kinases detected in MoAb 1-22-3 precipitates were higher
      than those in MoAb OX-7 precipitates. These results suggest that Thy-1 molecule
      transduces some signals also in rat mesangial cells.

PMID- 8870704
TI  - Methylprednisolone differentially regulates IL-10 and tumour necrosis factor
      (TNF) production during murine endotoxaemia.
AB  - IL-10 is an endogenous antiinflammatory cytokine that inhibits TNF biosynthesis
      and protects mice from lipopolysaccharide (LPS)-induced lethality. As synthetic
      glucocorticoids are widely used as antiinflammatory agents, we analysed the
      effects of methylprednisolone administration on IL-10 biosynthesis during murine
      endotoxaemia. We found that low doses of methylprednisolone (2-10 mg/kg) markedly
      inhibited TNF production but did not affect serum levels of IL-10, while a high
      methylprednisolone dose (50 mg/kg) increased LPS-induced IL-10 levels. In
      parallel, we observed that LPS-induced IL-10 production is TNF-independent in
      this experimental setting. Experiments conducted in vitro indicated that
      methylprednisolone (from 0.01 to 100 micrograms/ml) also increased the
      biosynthesis of IL-10 by LPS-activated mouse peritoneal macrophages. We conclude
      that methylprednisolone differentially regulates IL-10 and TNF production induced
      by LPS both in vivo and in vitro at the macrophage level.

PMID- 8870705
TI  - Inhibitory effect of salmeterol on the respiratory burst of adherent human
      neutrophils.
AB  - Human neutrophils, plated in fibronectin-coated wells and stimulated with N
      formyl-methionylleucyl-phenylalanine (fMLP), were found to undergo a massive and
      prolonged respiratory burst, as measured by monitoring superoxide production. The
      beta 2-agonist salmeterol inhibited the respiratory burst in a dose-dependent
      manner. In contrast, salbutamol was ineffective. Moreover, the neutrophil
      respiratory burst was partially suppressed by prostaglandin E2 (PGE2) and the
      phosphodiesterase type IV (PDE-IV) inhibitor RO 20-1724. When salmeterol was used
      in combination with PGE2 or RO 20-1724, additive inhibitory effects were
      observed. The inhibitory activity of salmeterol was not reversed in the presence
      of the beta-blocker propranolol, and did not correlate with its ability of
      increasing cyclic AMP (cAMP) levels. Finally, the compounds used did not affect
      neutrophil adherence to fibronectin-coated wells. The results suggest that
      salmeterol is capable of down-regulating the neutrophil oxidative response to
      fMLP, also of co-operating with PGE2 and PDE-IV inhibitor RO 20-1724 in a manner
      not related to its beta 2-receptor binding activity. In other words, salmeterol
      displays neutrophil-directed effects, susceptible to be amplified by natural
      mediators such as PGE2 or PDE-IV inhibitors, consistent with possible anti
      inflammatory properties of the drug.

PMID- 8870706
TI  - The mode of action of treatment by IgG of haemolytic anaemia induced by an anti
      erythrocyte monoclonal antibody.
AB  - In order to gain insight into the mechanisms by which the infusion of IgG can
      improve some autoimmune diseases, we induced haemolytic anaemia in mice by the
      injection of anti-erythrocyte MoAbs derived from NZB mice by S. Izui (Geneva).
      The IgG1 antibody 31-9D induces anaemia by erythrocyte sequestration in the
      spleen and liver, whereas the IgG2a antibody 34-3C triggers erythrophagocytosis
      (Shibata et al., Int Immunol 1990. 2:1133). Treatment of mice with pools of
      either human or mouse IgG clearly attenuated the anaemia induced by 34-3C, but
      not by 31-9D. Similar protection was obtained with human monoclonal IgGs from
      myeloma patients. Prior absorption by mouse erythrocytes did not affect the
      efficacy of the injected IgG. Treatment with Fc fragments also reduced the
      anaemia. In vitro experiments confirmed that 34-3C, but not 31-9D, triggered
      erythrocyte phagocytosis by murine macrophages. This process was completely
      inhibited by addition of polyclonal or myeloma IgG or of human Fc fragments.
      These results indicate that, in this model of autoimmune pathology, the
      protective effect of IgG is mediated by its interaction with the macrophage Fc
      receptors.

PMID- 8870707
TI  - Chronic smoke exposure alters the phenotype pattern and the metabolic response in
      human alveolar macrophages.
AB  - Smoking induces a chronic inflammatory process in the lower respiratory tract,
      where the alveolar macrophages (AM) are the main phagocytes. In the present
      study, the expressions of different membrane glycoproteins (CD11abc, CD71, CD54,
      CD14 and CD16) were determined by flow cytometry in AM from smokers and non
      smokers after quenching of the intracellular autofluorescence. The metabolic
      activity of the AM was quantified as a functional test. The expressions of CD11a,
      CD54 and CD71 were higher in non-smokers' AM than in smokers'. The expressions of
      CD11b and CD16 were similar between the groups, while the CD11c was higher in
      smokers' AM compared with non-smokers'. The expression of CD14 was weak in both
      groups, therefore there was no clear-cut difference between the background and
      positively labelled cell populations. The metabolic response after in vitro
      stimulation with the phorbol ester phorbol myristate acetate (PMA) was higher in
      non-smokers' than in smokers' AM. Our results indicate that chronic exposure to
      tobacco smoke influences both the expression of AM membrane antigens and the
      metabolic activity. AM from non-smokers express a phenotype more related to cell
      proliferation and an accessory function. In contrast, receptors reflecting
      adhesion and phagocytosis were unaltered or even increased in smokers' AM. The
      findings suggest a functional change in the AM population after chronic smoke
      exposure.

PMID- 8870708
TI  - Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar
      macrophages in airway diseases.
AB  - Asthma and chronic bronchitis are associated with airway remodelling, and airway
      macrophages are present in bronchial inflammation. TGF-beta and fibronectin
      released by alveolar macrophages possess a fibrogenic potency. The potential role
      of alveolar macrophages in airway remodelling was studied in asthma and chronic
      bronchitis by the release of TGF-beta and fibronectin. Alveolar macrophages were
      isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14
      chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or
      concanavalin A (Con A)-induced release of TGF-beta and fibronectin was measured
      by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release
      greater amounts of TGF-beta and fibronectin than those from asthmatic and control
      subjects. Alveolar macrophages from asthmatics release greater amounts of TGF
      beta and fibronectin than those from control subjects. The spontaneous release of
      TGF-beta is significantly correlated with that of fibronectin. Fibronectin
      release was significantly reduced after LPS stimulation, and TGF-beta release was
      significantly increased after LPS stimulation, except in chronic bronchitis
      patients. Con A increased the release of TGF-beta in cells from normal subjects.
      This study suggests that activated macrophages play a role in airway remodelling
      in chronic bronchitis and to a lesser extent in asthma.

PMID- 8870709
TI  - Lower serum concentrations of cytokines in elderly patients with pneumonia and
      the impaired production of cytokines by peripheral blood monocytes in the
      elderly.
AB  - It has been well documented that the immune function declines with age; however,
      little is known about the monocyte/macrophage function of age. In the present
      study, we measured the concentrations of granulocyte colony-stimulating factor (G
      CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 beta,
      tumour necrosis factor-alpha (TNF-alpha), IL-8 and monocyte inflammatory protein
      1 alpha (MIP-1 alpha) in sera from 15 elderly patients and 22 young patients with
      pneumonia, in the acute phase and after recovery, by ELISA. In addition, we
      measured the concentrations of these cytokines in culture supernatants from
      lipopolysaccharide (LPS)-stimulated peripheral blood monocytes from normal
      healthy elderly subjects and young subjects in order to clarify the ability of
      the elderly to produce these cytokines. The concentrations of these cytokines in
      sera from old patients and in those from young patients obtained in the acute
      phase were higher than those in sera obtained after recovery phase. However, the
      concentrations of these cytokines in the acute phase were lower in elderly
      patients compared with those in young patients. Serum concentrations of cytokines
      did not appear to be associated with clinical outcome. In the production of these
      cytokines by monocytes, LPS-stimulated monocytes from healthy normal elderly
      subjects produced smaller amounts of G-CSF, GM-CSF, IL-1 beta, TNF-alpha, IL-8
      and MIP-1 alpha than those from healthy normal young subjects. These results with
      the impaired production of these cytokines in the elderly may prove, at least in
      part, the characteristic features of host defence mechanisms of the elderly.

PMID- 8870710
TI  - Characterization of type 1 and type 2 cytokine production profile in physiologic
      and pathologic human pregnancy.
AB  - Antigen- and mitogen-stimulated cytokine production by peripheral blood
      mononuclear cells (PBMC) of 50 pregnant women and 31 age- and sex-matched non
      pregnant controls were analysed to determine whether changes in cytokine
      production occur during normal and pathologic human gestation. The pregnant
      women, consecutively enrolled during a 3-month period, were undergoing a normal,
      non-pathologic pregnancy at the time of entry into the study, and underwent
      ultrasound examination to ascertain the exact week of pregnancy and the vitality
      of the fetus. Forty of the 50 pregnancies (80%) terminated physiologically with
      the birth of normal babies. Spontaneous abortions were observed in 5/50 (10%)
      women, and five women gave birth to newborns small for gestational age (SGA). A
      decrease in the production of IL-2 and interferon-gamma (IFN-gamma) accompanied
      by an increase in production of IL-4 and IL-10, was observed in normal pregnancy,
      with the lowest quantities of IL-2 and IFN-gamma and the highest quantities of IL
      4 and IL-10 present in the third trimester of pregnancy. Statistically
      significant increased production of both IL-2 and IFN-gamma and reduced
      production of IL-10 characterized pathologic pregnancies and distinguished them
      from normal pregnancies. These preliminary data suggest that a type 2 cytokine
      profile may be associated with normal human pregnancy, whereas the lack of a
      dominant type 2 cytokine profile may be indicative of a pathologic pregnancy.

PMID- 8870711
TI  - In vivo effects of cytokines on psoriatic skin grafted on nude mice: involvement
      of the tumour necrosis factor (TNF) receptor.
AB  - Following engraftment of human involved psoriatic skin to nude mice there is a
      partial normalization of pathology associated with a loss of inflammatory
      leucocytes. However, the epidermis remains hyperproliferative, which may reflect
      a primary defect. The roles of TNF-alpha, IL-1 and IL-6 in epidermal
      hyperproliferation of grafted psoriatic lesions were investigated. Before and
      after treatment, grafts were analysed to determine epidermal thickness and
      labelling index (LI). HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and TNF
      receptor (TNF-R; p75 and p55) expression were determined by immunoperoxidase
      staining. Psoriatic epidermis was found consistently to be negative for p55 TNF-R
      and p75 TNF-R before grafting. Following engraftment, TNF-R-positive cells (i.e.
      p55 by keratinocytes; p75 by epidermal dendritic cells) were identified
      throughout the epidermis. Higher numbers of p75 TNF-R epidermal dendritic cells
      were found in grafts following a course of TNF-alpha, IL-6 or IL-1 treatment. The
      p55 form of the TNF-R expressed by keratinocytes was significantly elevated after
      treatment with TNF-alpha or IL-6. HLA-DR and ICAM-1 were also expressed in these
      grafts. TNF-alpha, anti-IL-1, and anti-IL-6 treatment induced a marked decrease
      in the epidermal thickness and LI of psoriatic graft tissue, correcting the
      hyperproliferation associated with psoriatic epidermis. Supraphysiological levels
      of TNF-alpha may saturate and consequently down-regulate their own receptors,
      leading to a paradoxical inhibitory effect.

PMID- 8870713
TI  - IL-3 derived from CD4+ T cells is essential for the in vitro expansion of mast
      cells from the normal adult mouse spleen.
AB  - A null cell line (SCM1) was established by a culture of spleen cells (SC) from
      normal adult C57B1/6 mice with complete medium alone for 10 days and followed by
      weekly cultures with a 25% WEHI-3 cell culture supernatant. Phenotype analysis
      showed that the SCM1 cells were negative for CD3, Thy1.2, B220, Mac-1, Gr-1,
      NK1.1 and MHC class II, but were positive for MHC class I, Fc gamma RII/ III, Fc
      epsilon RI, c-kit and the receptor against wheat germ agglutinin. These findings
      suggested that the SCM1 cells were mast cells. In an in vitro proliferation
      assay. SCM1 cells proliferated in the presence of either IL-3 or stem cell factor
      (SCF), but not in the presence of IL-4, whereas IL-4 showed an augmenting effect
      on their proliferation in the presence of either IL-3 or SCF. In analysing the
      mechanism by which such mast cells could be expanded from normal adult mouse SC,
      the addition of anti-IL-3 MoAb, but not anti-SCF MoAb, into the initial culture
      inhibited the subsequent expansion of either IL-3-or SCF-responding cells. The
      prior depletion of CD4+ T cells abrogated the capacity of the SC to enhance the
      expansion of SCF-responding cells, and this inability was restored by the
      addition of IL-3. Moreover, the culture supernatant of normal adult SC alone
      contained considerable levels of IL-3. Taken together, our findings suggest that,
      in an in vitro culture, CD4+ T cell-derived IL-3 therefore enhances the expansion
      of mast cells from the normal adult mouse spleen.

PMID- 8870712
TI  - Induction of IL-4 by platelet-activating factor.
AB  - Platelet-activating factor (PAF) is a phospholipid inflammatory mediator which is
      synthesized by a variety of cells, including monocytes, endothelial cells, mast
      cells and neutrophils. PAF acts via a recently cloned PAF receptor, present on
      monocytes and endothelial cells, but not on non-activated lymphocytes. IL-4 is
      mainly produced by T lymphocytes, and belongs to the Th2 subset of T helper
      cells. IL-6 is mainly a monocyte/macrophage-derived cytokine with multiple
      proinflammatory effects. We here report that PAF induces IL-4 production, as
      determined by ELISPOT. Antibodies to MHC class II inhibited the IL-4 stimulatory
      effects of PAF. PAF also had the capacity to induce IgA production, as determined
      by ELISPOT, and IL-6 production in peripheral blood mononuclear cells (PBMC) as
      determined by ELISA. These PAF-mediated effects were completely inhibited by a
      specific PAF-receptor antagonist, WEB 2170. Taken together, our data indicate
      that PAF activates T lymphocytes to IL-4 production by an indirect, monocyte
      dependent mechanism dependent on MHC class II. PAF also enhances antibody
      formation and IL-6 production from PBMC. These findings indicate that PAF
      activates immune-competent cells, which may be of importance in inflammatory
      diseases such as asthma, vasculitis and atherosclerosis.

PMID- 8870714
TI  - Complement plays an essential role in shock following intestinal ischaemia in
      rats.
AB  - Intestinal ischaemia lasting more than 30 min in rats causes fatal systemic
      shock. Systemic shock was suppressed by preadministration of cobra venom factor
      (CVF), which reduced the serum complement to less than 5% of the normal level,
      indicating that complement is involved in the syndrome. After complement
      activation, anaphylatoxins such as C3a and C5a are generated, and their activity
      is restricted by carboxypeptidases which remove C-terminal arginine from such
      bioactive peptides. As expected, preadministration of a carboxypeptidase
      inhibitor enhanced the systemic shock induced by the intestinal ischaemia.
      However, when the complement level was suppressed by CVF treatment, no fatal
      systemic shock was induced by the intestinal ischaemia even with
      preadministration of the carboxypeptidase inhibitor. These results indicate that
      complement plays a crucial role in systemic shock induced by intestinal
      ischaemia, and that anaphylatoxins generated by the complement activation should
      be involved in induction of the shock syndrome.

PMID- 8870715
TI  - Beta 2-integrin/intercellular adhesion molecule (ICAM) expression in the normal
      human intestine.
AB  - The beta 2-integrin family of adhesion molecules and their ligands, the ICAM
      molecules, probably have an important role to play in the intestinal immune
      response. To date, any data published regarding the intestinal expression of beta
      2-integrins and ICAMs have mostly described only mucosal expression. The presence
      in the intestine of alpha d, a newly described beta 2-integrin molecule, has not
      yet been determined. To understand further the expression of these molecules in
      all layers of the intestine, a comprehensive study was undertaken in both normal
      colon and normal small intestine specimens from 15 patients (colon n = 15, and
      ileum n = 6) who underwent surgical resections. Immunohistochemistry was
      performed for CD18, CD11a, CD11b, CD11c, alpha d, ICAM-1, ICAM-2, and ICAM-3. The
      colon and small intestine cases were grouped separately and each of the mucosal,
      submucosal, muscle and adventitial layers were scored for expression. The beta 2
      integrin molecules were expressed by mononuclear cells in all layers of the
      bowel, predominantly in the mucosa and adventitia. CD11a showed the greatest
      mucosal expression and CD11b showed the greatest adventitial expression. alpha d
      exhibited expression in all bowel layers, as well, with most intense expression
      in the mucosa and adventitia. CD11c exhibited the least expression of all alpha
      subunit molecules. The expression of these alpha-chains at times appeared to be
      greater than that seen for CD18 (beta 2), raising the possibility of non-beta 2
      containing complexes (i.e. alpha-chains associating with an alternate beta
      chain). ICAM-1 was expressed on endothelium, particularly in the mucosa and
      rarely on mucosal mononuclear cells. ICAM-2 was predominantly on submucosal
      endothelium and rarely expressed in colon mucosa and never expressed in ileal
      mucosa. ICAM-3 was expressed by mononuclear cells throughout the bowel wall, but
      also on adventitial endothelium in selected cases. In summary, we are reporting a
      comprehensive immunohistochemical study of the differential expression of beta 2
      integrins, including the newly described alpha d molecule, and the ICAM molecules
      in all layers of normal human colon and ileum. We raise the possibility that a
      second beta 2-integrin beta subunit may exist, and we report that ICAM-3 is
      expressed on endothelium, particularly in the adventitial layer.

PMID- 8870716
TI  - Expression of functionally active alpha 4 beta 1 integrin by thymic epithelial
      cells.
AB  - We have investigated the expression and function of the VLA-4 heterodimer alpha 4
      beta 1, a member of the beta 1 integrin subfamily, on human thymic epithelial
      cells (TEC) derived from cortical epithelium. The expression of the alpha 4
      integrin chain was studied in four different cloned TEC lines derived from either
      fetal or post-natal human thymus by both flow cytometry and immunoprecipitation
      techniques with anti-alpha 4 MoAbs. All different cell lines assayed expressed
      significant levels of alpha 4, as revealed by their reactivity with MoAbs
      specific for distinct alpha 4 epitopes. The alpha 4 subunit expressed by TEC was
      associated to beta 1 but not to beta 1 chain, and displayed the characteristic
      80/ 70 kD pattern of proteolytic cleavage. The VLA-4 integrin in these cells was
      constitutively active in terms of adhesiveness to both fibronectin and vascular
      cell adhesion molecule-1 (VCAM-1). In addition, this heterodimer localized to
      punctate regions of the cell in the area of contact with the substratum, named
      point contacts assessed by staining with the anti-beta 1 activation epitope 15/7
      MoAb. According to the cortical origin of the TEC lines expressing VLA-4, human
      thymus sections stained with different anti-alpha 4 antibodies revealed the
      presence of cortical, and in smaller numbers medullary epithelial cells bearing
      alpha 4 integrin. The expression of alpha 4 in the thymus was also found in both
      adult and fetal rats, in which epithelial cells were also specifically stained.
      Altogether, our data show that VLA-4 is an additional component of the integrin
      repertoire of TEC, and suggest that it could have an important role in thymus
      epithelial cell-thymocyte interactions.

PMID- 8870718
TI  - Congress passes Animal Drug Availability Act.

PMID- 8870717
TI  - IL-2 signalling in T and natural killer (NK) cells associated with their class I
      non-restricted killing activity.
AB  - The signal transduction of IL-2 in NK cells and T cells was compared. On 5 min
      incubation of these cells with IL-2, we observed tyrosine phosphorylation of 105
      kD and 110-kD proteins in NK cells and of 95-kD and 110-kD proteins in T cells.
      The phosphorylation reached maximal levels in 15 min in both NK and T cells, but
      the levels were higher in NK cells, which showed superior killing against Daudi
      cells. With this phosphorylation, p52rhc was also tyrosine-phosphorylated and
      p21ras was activated by the short term (10 min) treatment of NK and T cells with
      IL-2. These signals were completely suppressed by anti-IL-2R beta MoAb, but only
      slightly suppressed by anti-IL-2R alpha MoAb, correlated with the suppression of
      the class-I-non-restricted cytotoxic activity of NK and T cells by these MoAbs.
      When tyrosine phosphorylation was inhibited by herbimycin A and genistein, the
      cytotoxic activities of NK and T cells were nearly completely suppressed. In
      addition, the tyrosine phosphorylation of JAK3 by IL-2 was more prominent in NK
      cells than in T cells, but JAK1, JAK2, STAT1 alpha, STAT2 and STAT3 were not
      phosphorylated. These results indicate that the IL-2 signal flows downstream via
      both ras-dependent and ras-independent pathways and that the superior killing
      activity of NK cells depends on their high susceptibility to protein tyrosine
      phosphorylation by IL-2.

PMID- 8870719
TI  - FeLV, FIV testing recommendations issued.

PMID- 8870720
TI  - Survey explores technician issues.

PMID- 8870724
TI  - Evaluating treatment for visceral leishmaniosis.

PMID- 8870725
TI  - Why not irradiate?

PMID- 8870726
TI  - Concerns about glass foreign body reactions.

PMID- 8870727
TI  - Concerns about possible drug interactions.

PMID- 8870728
TI  - Interpreting published results of extra-label drug use with special reference to
      reports of drugs used to correct problem behavior in animals.

PMID- 8870729
TI  - Marketing strategies to enhance the value of food animal veterinarians.

PMID- 8870730
TI  - The human side of veterinary medicine. Excellence.

PMID- 8870731
TI  - What is your diagnosis? Physeal fractures of the caput, greater trochanter and
      distal portion of the femur in a dog.

PMID- 8870732
TI  - What is your diagnosis? Bilateral fragmentation of the fourth maxillary premolar
      teeth attributable to impaction by adjacent teeth.

PMID- 8870733
TI  - Theriogenology question of the month. Transrectal palpation used to diagnose
      uterine torsion in a horse.

PMID- 8870734
TI  - Veterinarians, disabled clients, and assistance dogs.

PMID- 8870735
TI  - Changes in the number and geographic distribution of US veterinarians employed by
      public or corporate organizations, 1980-1990 and 1990-1995.

PMID- 8870736
TI  - Financial assessment of results of intervention to correct a housing-system
      problem on a dairy farm.
AB  - OBJECTIVE: To monitor effects that improvements in housing facilities would have
      on herd performance. Financial measures were calculated to estimate whether
      improvements resulted in an improved financial status for the farm. DESIGN:
      Prospective, observational study. ANIMALS: 160-cow dairy herd. PROCEDURE: Farm
      visits were conducted from 1990 to 1994. Areas for improvement were identified,
      and changes were recommended. Herd production and farm financial records were
      analyzed before, during, and after adoption of recommended changes. RESULTS:
      After improving facilities, somatic cell count was somewhat constant, but tended
      to decrease during the last 16 months of the study. During the last 8 months of
      the study, incidence for clinical cases of mastitis decreased to 3.3% per month.
      Reproductive variables improved dramatically after implementing use of a bull for
      breeding. Subjective evaluation of cow comfort and lameness indicated apparent
      improvements in each area. However, milk production remained fairly constant from
      January 1991 through December 1994. Review of the arm's financial status revealed
      that costs of production increased from 1990 through 1993, but decreased in 1994.
      Slow financial response to improvements were attributed to a large decrease in
      milk price in 1991 and a poor crop harvest in 1993. Thus, although progress was
      made toward financial stability, approximately 55% of the farm's assets
      (determined on a market-basis value) were represented by debt. CLINICAL
      IMPLICATIONS: It is important to monitor financial status when managing complex
      health problems that involve several aspects of a farm's operation.

PMID- 8870737
TI  - Frequency of argyrophilic nucleolar organizer regions in fine-needle aspirates
      and biopsy specimens from mast cell tumors in dogs.
AB  - OBJECTIVE: To determine for mast cell tumors in dogs whether frequency of
      argyrophilic nucleolar organizer regions (AgNOR) determined by examining fine
      needle aspirates (FNA) correlated with frequencies determined by examining biopsy
      specimens or with histologic grade. DESIGN: Case series. ANIMALS: 25 dogs with 32
      histologically confirmed tumors. PROCEDURE: Biopsy specimens and FNA were
      collected from each tumor. Histologic grade and AgNOR frequency were determined.
      RESULTS: Frequency of AgNOR in FNA was significantly correlated with frequency in
      biopsy specimens and was significantly associated with histologic grade of the
      tumor. CLINICAL IMPLICATIONS: Determining AgNOR frequency in FNA of mast cell
      tumors in dogs is a rapid, minimally invasive means of obtaining information that
      potentially could be used to help predict biological behavior of the tumor and to
      guide clinicians and owners in making decisions about further diagnostic tests
      and treatment.

PMID- 8870738
TI  - Streptococcal toxic shock syndrome in dogs.
AB  - OBJECTIVE: To determine the clinical, pathologic, and bacteriologic findings in
      dogs that developed severe invasive infections with group G streptococci (GGS)
      over a 6-month period in southern Ontario. DESIGN: Prospective case series.
      ANIMALS: 7 dogs n southern Ontario with severe streptococcal infection during a 6
      month period. PROCEDURE: Using pulsed-field gel electrophoresis, molecular typing
      of streptococcal isolates was performed. Isolates were examined for the M protein
      gene emm1.0, pyrogenic exotoxin genes speA, speB, speF, hyaluronic acid synthase
      genes hasA, hasB, and for C5a peptidase gene scpA by use of DNA probes or
      polymerase chain reaction. RESULTS: 3 dogs with streptococcal shock without
      necrotizing fasciitis died or were euthanatized within 48 hours of admission,
      whereas 4 dogs with streptococcal shock and necrotizing fasciitis survived
      following surgical debridement, supportive medical treatment, and treatment with
      antibiotics. Of the 6 Lancefield group G streptococcal isolates available for
      characterization, 5 were Streptococcus canis and 1 had characteristics of group G
      streptococcal strains of human origin. Results of molecular typing indicated that
      isolates were unrelated to each other. Examination of the canine isolates for
      putative virulence genes found in human group A streptococci resulted in
      identification of the emm1.0 gene only in 1 of the isolates. The canine isolates
      otherwise lacked virulence genes associated with human group A streptococcal
      toxic shock infections. CLINICAL-IMPLICATIONS: The development of severe invasive
      infection in dogs resulting from GGS indicates that a virulent form of GGS has
      developed in southern Ontario.

PMID- 8870739
TI  - Relationship between physical signs of elbow dysplasia and radiographic score in
      growing Rottweilers.
AB  - OBJECTIVE: To examine the relationship between physical signs of elbow dysplasia
      and radiographic appearance of the elbow joints in growing dogs. DESIGN:
      Prospective study. ANIMALS: 55 Rottweiler pups. PROCEDURE: Owners of clinically
      normal Rottweiler pups were contacted through breed clubs in 3 Australian states
      and asked to participate in the study. All those offering to participate were
      included. PROCEDURE: The first physical examination was performed when pups were
      3 months old and included a lameness evaluation and palpation of the elbow
      joints. Physical examinations were repeated when pups were 5, 6, 9, and 12 months
      old. Radiographs of the elbows were obtained at 6 and 12 months. Relationships
      among lameness, decreased range of movement, signs of pain, and radiographic data
      related to elbow dysplasia were examined. RESULTS: Elbow dysplasia caused
      clinical lameness in only 3 dogs but 57% of dogs developed radiographic signs of
      elbow dysplasia by 12 months of age. A grade-2 radiographic score at 12 months of
      age was significantly associated with clinical elbow dysplasia. CLINICAL
      IMPLICATIONS: Elbow dysplasia has a prevalence of > 50% in certain breed
      populations. This study supports radiographic screening at 12 months of age,
      accompanied by physical examination to detect clinical elbow dysplasia.

PMID- 8870740
TI  - Intradermal reactivity to various insect and arachnid allergens among dogs from
      the southeastern United States.
AB  - OBJECTIVE: To compare cutaneous reactivity to insect and arachnid allergens in
      clinically normal (control) and allergic dogs in the southeastern United States.
      DESIGN: Prospective, controlled study. ANIMALS: 26 clinically normal dogs and 82
      allergic dogs from the southeastern United States. PROCEDURE: Intradermal skin
      testing with various dilutions of 13 insect and arachnid allergens was performed
      on control dogs to establish skin threshold concentrations (ie, concentrations to
      which < 25% of the dogs had positive reactions). These established threshold
      concentrations were then used to test allergic dogs for reactivity. Prevalence of
      single and multiple insect and arachnid reactions were determined. RESULTS: Flea
      allergen was the only allergen that caused a significantly higher prevalence of
      positive reactions in allergic dogs than in control dogs. CLINICAL IMPLICATIONS:
      Flea hypersensitivity is the most important arthropod hypersensitivity in dogs.
      The importance of reactivity to insect and arachnid allergens other than flea
      allergen can be determined only when prevalence of positive reactivity has been
      determined in an appropriate regional control group of dogs.

PMID- 8870741
TI  - Heart failure in a macaw with atherosclerosis of the aorta and brachiocephalic
      arteries.
AB  - A female severe macaw (Ara severa) that was at least 11 years old was evaluated
      for sudden onset of exercise intolerance and dyspnea. Radiography revealed a
      large heart silhouette, an increase in prominence of the brachiocephalic
      arteries, and a diffuse increase in opacity of the lungs. Lateral nonselective
      angiography revealed dilatation of both chambers of the right side of the heart
      and incomplete emptying of the right atrium. Alterations in the shape and
      position of the left-side heart chambers and reduction in blood flow through the
      brachiocephalic arteries and aorta were identified. Despite treatment, the bird
      died suddenly 2.5 months after the first episode of dyspnea. At necropsy, severe
      atherosclerosis of the aorta and brachiocephalic arteries, dilatation of all
      heart chambers, pulmonary edema, and severe hepatic centrolobular atrophy and
      fibrosis were identified. Correlation between the angiography and necropsy
      findings suggested that angiography could be an important diagnostic tool for the
      detection of cardiovascular disease in birds.

PMID- 8870742
TI  - Cutaneous epitheliotropic lymphoma in a ferret.
AB  - An 8-year-old spayed female ferret was examined for diffuse generalized alopecia,
      erythema, erosions, crusts, and ulcerated plaques that were nonresponsive to long
      term administration of corticosteroids. Cutaneous epitheliotropic lymphoma was
      diagnosed on the basis of histologic examination of skin biopsy specimens.
      Neoplastic cells were determined to be of T-lymphocytic origin by results of
      immunohistochemical staining with a rabbit anti-CD3 monoclonal antibody.
      Additional laboratory abnormalities detected included anemia, azotemia,
      isosthenuria, pyuria, and bacteriuria. Treatment included isotretinoin and
      amoxicillin trihydrate plus clavulanate potassium administered orally, and
      oatmeal-based shampoos. Isotretinoin was tolerated well and cutaneous lesions
      resolved after 60 days of treatment, but pretreatment azotemia worsened and the
      ferret was euthanatized. Necropsy revealed cutaneous epitheliotropic lymphoma,
      pyelonephritis, and interstitial nephritis. Renal disease most likely was caused
      by immunosuppression secondary to chronic treatment with corticosteroids and
      aging. Isotretinoin, although not curative, may be useful for the palliative
      treatment of cutaneous epitheliotropic lymphoma in ferrets.

PMID- 8870743
TI  - Closed reduction and type-II external fixation of comminuted fractures of the
      radius and tibia in dogs: 23 cases (1990-1994).
AB  - OBJECTIVE: To describe a technique for closed reduction of and application of a
      type-II external fixator to comminuted fractures of the radius and tibia in dogs
      and to evaluate outcome of the technique in a series of client-owned dogs.
      DESIGN: Retrospective case series. ANIMALS: 23 dogs that underwent closed
      reduction of severely comminuted (> or = 5 fragments); mid-diaphyseal radial (n =
      9); and tibial (n = 14) fractures and stabilization with a type-II external
      fixator. PROCEDURE: Radiographs were made postoperatively and every 4 to 6 weeks
      until the fixator was removed. The effect of type of fracture (open vs closed),
      type of pins (threaded vs smooth), and number of fixation pins on surgery time,
      time between surgery and development of bridging callus, and time between surgery
      and removal of the fixator was evaluated using one-sided Student's t-tests.
      RESULTS: 21 fractures healed after a single surgery. Two dogs with radial
      fractures required a second procedure because of complications. All fractures
      healed with the original fixation device in place. Mean time between surgery and
      the development of bridging callus was 11.4 weeks (range, 4 to 22 weeks), and
      mean time between surgery and fixator removal was 14.7 weeks (range, 4 to 27
      weeks). Type of fracture, type of pins, and number of fixation pins did not have
      a significant effect on surgery time, time to development of bridging callus, or
      time to fixator removal. CLINICAL IMPLICATIONS: Closed reduction and application
      of a type-II external fixator was an effective method of treating severely
      comminuted radial and tibial fractures.

PMID- 8870744
TI  - Survival analysis approach to risk factors associated with hyperlipemia in
      donkeys.
AB  - OBJECTIVE: To investigate the effect of gender, body condition, and age as risk
      factors for the development of hyperlipemia in a population of donkeys. DESIGN:
      Retrospective survival analysis. ANIMALS: 130 donkeys with hyperlipemia from a
      source population of 4,126 donkeys. PROCEDURE: A Kaplan-Meier product limit
      survival method was used to evaluate the effect of gender and body condition on
      the probability of diagnosis of clinical hyperlipemia. Cox's proportional hazard
      model was used to evaluate the risk of being diagnosed with hyperlipemia
      controlling for gender, body condition, and age at entry into the population.
      RESULTS: Female donkeys and donkeys of obese body condition were more at risk for
      developing hyperlipemia than males or those of moderate or poor body condition,
      respectively. None of the females in the study was pregnant. Donkeys were more
      likely to become hyperlipemic soon after entering the source population.
      Investigation of the effect of age at entry into the population indicated that
      older animals were at higher risk than younger animals and, controlling for age,
      the hazard ratios associated with being female and being overweight were 2 and
      1.5, respectively. CLINICAL IMPLICATIONS: Although pregnancy and lactation are
      widely acknowledged as risk factors for hyperlipemia, in this population, females
      and obese donkeys were at highest risk, regardless of pregnancy status. Risk was
      greatest around the time donkeys first entered the source population. Control of
      body condition, reduction of stress, and close monitoring of high-risk donkeys
      might reduce incidences of, or allow more timely intervention for, this
      potentially fatal condition.

PMID- 8870745
TI  - Acute small intestinal injury associated with hematomas in the mesentery of four
      horses.
AB  - Four horses were evaluated for clinical signs consistent with small intestinal
      disease. During exploratory surgery, primary hematomas in the mesentery were
      found in 2 horses. The third horse developed a hematoma secondary to a mesenteric
      rent, whereas in the fourth horse, a hematoma developed secondary to
      strangulation of the bowel by a mesenteric lipoma. Two horses were euthanatized
      at surgery, because the extensive nature of the hematoma precluded ligation and
      there was substantial risk of continued hemorrhage postoperatively. The remaining
      horses recovered from surgery but developed complications. One horse developed
      functional ileus and required a second surgery to decompress the bowel, whereas
      the second horse eventually was euthanatized for severe, recurrent signs of
      colic. Clinical signs and management of small intestinal lesions related to
      volvulus, epiploic entrapment, intramural hematoma, mesenteric rent, and
      intussuception have been described. To our knowledge, reports of small intestinal
      infarctions secondary to hematomas in the mesentery have not been published.
      Primary hematomas in the mesentery should be included in the differential
      diagnoses for horses examined for signs of depression, anorexia, and progressive
      signs of colic.

PMID- 8870747
TI  - Papillomatous digital dermatitis in 458 dairies.
AB  - OBJECTIVE: To estimate prevalence of papillomatous digital dermatitis (PDD) in
      California dairies during 1993, to describe temporal and spatial patterns of PDD
      and response of cows to treatment, and to evaluate herd-related risk factors for
      PDD. DESIGN: Epidemiologic survey. SAMPLE POPULATION: All southern California
      dairies and a 50% random sample of the rest of California dairies. PROCEDURE: A
      questionnaire was mailed to managers of 1,429 selected dairies. RESULTS:
      Prevalence of PDD during 1993 was significantly higher for dairies in the south
      (75.3%) and central (68.8%) regions, compared with north coast (33.3%) and north
      (23.1%) regions of the state. Herd mean and median proportions of affected cows
      in PDD-affected herds were 11.6 (SEM = 0.9) and 5%, respectively. Most (74%)
      dairy managers surveyed observed PDD for the first time during 1992 or 1993.
      Highest PDD activity was reported as taking place in summer in the south and in
      fall and winter in the north coast and north regions; an obvious pattern was not
      determined for the central region. CLINICAL IMPLICATIONS: PDD was widespread in
      California dairies during 1993 and affected a high proportion of cows, especially
      in the south and central regions of the state.

PMID- 8870746
TI  - Evaluation of udder health and mastitis in llamas.
AB  - OBJECTIVE: To investigate intramammary infections in llamas, identify the
      pathogens responsible, and determine whether effects of intramammary infection
      could be detected by use of mastitis indicator tests commonly used for cows.
      DESIGN: Observational study. ANIMALS: 100 llamas on 10 farms. PROCEDURE: Milk
      samples were evaluated by bacterial culturing and by determination of somatic
      cell count (SCC), using direct microscopic and automated counting methods,
      California Mastitis Test score, pH, and N-acetyl-beta-d-glucosaminidase activity.
      Correlation coefficients were determined among the various mastitis indicator
      tests, and test results were determined for milk from infected and uninfected
      glands. RESULTS: Evidence of intramammary infection was evident in 76 of 369
      (21%) milk samples, with 54 of 94 (57%) llamas having at least 1 infected gland.
      Staphylococcus sp other than Staphylococcus aureus were the predominant
      pathogens. None of the llamas had clinical signs of mastitis, and significant
      differences were not detected in SCC, California Mastitis Test score, pH, or N
      acetyl-beta-d-glucosaminidase activity between infected and uninfected samples.
      California Mastitis Test scores were negative or trace for 307 of 313 (98%)
      samples, and SCC were low. In contrast, pH and N-acetyl-beta-d-glucosaminidase
      activity of milk from uninfected glands were higher than values reported for milk
      from uninfected cows, and neither variable was significantly correlated with the
      number of somatic cells in samples of llama milk. CLINICAL IMPLICATIONS: Although
      intramammary infections develop in llamas, inflammation (mastitis) appears to be
      rare. Values for mastitis indicator tests used for cows cannot be directly
      extrapolated to llamas. Subclinical mastitis is apparently not an important
      problem in llamas in the United States.

PMID- 8870748
TI  - Abomasal bloat associated with Sarcina-like bacteria in goat kids.
AB  - An epizootic of abdominal tympany in goat kids as a result of abomasal bloat
      associated with a short duration of clinical signs was fatal in over 200 kids.
      Histologic examination of sections of abomasum revealed high numbers of bacteria
      that were morphologically identical to Sarcina sp. Sarcina sp are anaerobic, gas
      producing organisms that could cause abomasal bloat. Other reports have proposed
      that abomasal bloat is caused by abnormal abomasal flora; we propose that in the
      goat kids reported here, Sarcina sp may represent the abnormal flora.

PMID- 8870749
TI  - Use of fluoxetine for the treatment of stereotypical pacing behavior in a captive
      polar bear.
AB  - Stereotypical behaviors are common in captive animals, particularly captive polar
      bears. Effects of oral administration of fluoxetine on chronic stereotypical and
      typical behaviors in a captive polar bear were monitored. Fluoxetine treatment
      terminated stereotypic pacing behavior, facial tic, and huffing/coughing
      activity. The expression of typical polar bear behaviors was not affected by
      fluoxetine treatment, although the proportion of time spent engaged in typical
      behaviors changed during the course of the observation period. Response of the
      bear to fluoxetine treatment indicated that pharmacologic manipulation of the
      serotonergic system can safely eliminate stereotypical behaviors in captive polar
      bears.

PMID- 8870750
TI  - A tap in time?

PMID- 8870751
TI  - Statistical methodology and effective emergency medicine: what is the connection?

PMID- 8870752
TI  - Thrombolysis for acute cerebral infarction: its time has come.

PMID- 8870754
TI  - Delayed diagnosis of thoracolumbar fractures in multiple-trauma patients.
AB  - OBJECTIVES: To determine the frequency of delayed diagnosis of major
      thoracolumbar vertebral fractures (T-L Fxs) in ED multiple-trauma patients, and
      to determine the differences between cases of delayed and nondelayed diagnoses of
      T-L Fx. METHODS: A retrospective chart review was conducted of 181 trauma
      patients with 310 major T-L Fxs (compression, burst, or chance Fxs or
      dislocations). Data collected included the time of the diagnosis of T-L Fx, the
      patient's clinical presentation in the ED, the mechanism of injury, and the
      outcome. RESULTS: Of the 181 patients with major T-L Fxs, 138 were diagnosed in
      the ED (nondelayed group), and 43 were diagnosed after the patient left the ED
      (delayed group). Of these, 33 cases occurred in unstable patients requiring
      emergent medical imaging and/or operation, 7 occurred when emergency physicians
      failed to detect subtle compression Fxs on ED radiographs, and 3 occurred in
      stable patients who were not radiographed in the ED. The delayed group were more
      often critical, and hypotensive, and had lower Glasgow Coma Scale (GCS) scores
      than did the nondelayed group. The delayed group patients also had more cervical
      spine injuries, multiple noncontiguous spinal Fxs, high-energy mechanisms of
      injury, and direct blunt assaults to the back than did the nondelayed group
      patients. There were 13 patients with T-L Fxs, GCS scores = 15, and normal back
      examinations. There were 43 patients who had neurologic deficits associated with
      their injuries; 11 patients with incomplete cord lesions progressed, including 3
      in the delayed group. CONCLUSIONS: A delay in the diagnosis of T-L Fx in
      hospitalized trauma patients is frequently associated with an unstable patient
      condition that necessitates higher-priority procedures than ED T-L spine
      radiographs. Such patients should receive spinal precautions until more complete
      evaluation can be performed. The decision to selectively radiograph T-L spines in
      multiple-trauma patients should consider the mechanism of injury, the presence of
      possible confounders to physical examination, and clinical signs and symptoms of
      back injury.

PMID- 8870753
TI  - Subarachnoid hemorrhage diagnosis: lumbar puncture is still needed when the
      computed tomography scan is normal.
AB  - OBJECTIVES: To determine the sensitivity of third-generation CT scanners for
      diagnosed nontraumatic subarachnoid hemorrhage (SAH) and to assess the impact of
      symptom duration on sensitivity. METHODS: A retrospective chart review was
      performed in a university-affiliated tertiary care hospital with an annual ED
      volume of > 100,000 patients. The target population was all patients who
      presented to the ED from January 1991 to September 1994 with symptoms suggestive
      of SAH and who had a final diagnosis of nontraumatic SAH based on either a
      positive CT scan or positive spinal fluid analysis. Patients referred from
      outside facilities were included if they had a CT done at the study site. All CT
      scans were done using third-generation scanners. Official CT scan reports were
      used to categorize scans as positive or negative. RESULTS: There were 140
      patients identified with SAH, with a mean age of 56 years (range 10-88). The
      sensitivity of CT in the diagnosis of nontraumatic SAH when performed at or
      before 12 hours of symptom duration was 100% (80/80), and 81.7% (49/60) after 12
      hours of symptom duration (95% CI 95-100% and 69.5-90.4%, respectively; p <
      0.0001). Eleven of the 140 patients had a negative CT and positive spinal fluid
      analysis, yielding an overall sensitivity of 92.1% (129/140). CONCLUSION: The
      sensitivity of third-generation CT scans for SAH decreases with time from the
      onset of symptoms. In this sample population, CT was able to detect all patients
      scanned < or = 12 hours after symptom onset. Although the study demonstrated good
      sensitivity of CT scan reports for SAH when the scan was performed after < or =
      12 hours of symptom onset, additional real-time experience is needed to better
      define the potential risk of a missed SAH should this population not receive the
      customary lumbar puncture examination in the setting of a negative CT scan.

PMID- 8870755
TI  - Out-of-hospital administration of mannitol to head-injured patients does not
      change systolic blood pressure.
AB  - OBJECTIVE: To determine the effect of out-of-hospital mannitol administration on
      systolic blood pressure (BP) in the head-injured multiple-trauma patient.
      METHODS: This was a prospective, randomized, double-blind, placebo-controlled
      clinical trial involving a university-based helicopter air medical service and
      level-1 trauma center hospital. Endotracheally intubated head-trauma victims with
      Glasgow Coma Scale (GCS) scores < 12 were enrolled from November 22, 1991, to
      November 20, 1992, if evaluated by the participating aeromedical transport team
      within 6 hours of injury. Patients were excluded if they were < 18 years old, had
      already received mannitol or another diuretic, were potentially pregnant, or were
      receiving CPR. All patients were intubated prior to study drug (mannitol [1 g/kg]
      or normal saline) use. Pulse and BP were measured every 15 minutes for 2 hours
      following study drug administration. RESULTS: A total of 44 patients were
      enrolled. After exclusion of 3 patients who did not meet all inclusion criteria,
      there were 20 patients in the mannitol group and 21 patients in the placebo
      group. The groups were similar at baseline in age, pulse, systolic BP (baseline
      mannitol: 124 +/- 47 mm Hg; placebo: 128 +/- 32 mm Hg), GCS score, and Injury
      Severity Scale score. Systolic BP did not change significantly throughout the
      observation period in either group. This study had 83% power to detect a mean
      systolic BP drop to < 90 mm Hg. CONCLUSION: Out-of-hospital administration of
      mannitol did not significantly change systolic BP in this group of head-injured
      multiple-trauma patients.

PMID- 8870757
TI  - The frequency of unsuspected minor illness or injury in intoxicated patients.
AB  - OBJECTIVE: To determine the frequency of unsuspected minor illness or injury in a
      group of patients frequently seen in the ED for acute intoxication. METHODS: The
      medical records of the 20 patients seen most frequently in the ED for acute
      intoxication in 1993 were reviewed for the number of ED visits for intoxication,
      the number of associated documented episodes of minor trauma or illness, the
      extent of ED workup of discovered illness or injury, and patient disposition from
      the ED. RESULTS: The 20 study patients were evaluated in the ED 1,858 times in
      1993 for acute intoxication, a mean of 92.5 visits/patient (+/- 26.6). The most
      frequent injury was minor trauma above the neck, occurring a mean of 9 times (+/-
      3.6) in each of the study patients during 1993. Evaluation included repeated
      neurologic examinations and frequent radiography of the cervical spine (n = 80),
      skull (n = 5), facial bones (n = 6), and mandible (n = 5). A limited number of
      head CT scans also were done (n = 8). The most frequent minor illnesses were
      gastritis (n = 7), managed with hydration, and mild hypothermia (n = 6), managed
      with passive rewarming. CONCLUSIONS: The incidence of unsuspected minor illness
      or injury in this patient group was substantial. While most unsuspected medical
      problems had little clinical significance, some were potentially dangerous, and
      some necessitated hospitalization (e.g., hypothermia, hematemesis, and
      respiratory depression).

PMID- 8870756
TI  - Intrasound vibration testing in acute ankle injuries.
AB  - OBJECTIVES: To determine the accuracy of intrasound vibration testing (IVT) in
      comparison with plain radiography in the diagnosis of acute ankle fractures.
      METHODS: A group-sequential, nonrandomized, double-blind, observational study
      design was used. A convenience sample of patients were studied, aged > or = 10
      years, with acute ankle injuries, undergoing ankle radiography, evaluated at a
      community teaching hospital ED. Excluded were cases involving injuries of > 24
      hours' duration, inadequate documentation, protocol violation, or positive IVT on
      the uninjured ankle. IVT was performed with the intrasound apparatus placed on
      the anterior and posterior aspects of the medial and lateral malleoli of the
      uninjured and injured ankles; positive IVT was defined as patient withdrawal
      secondary to pain. RESULTS: Of 105 patients enrolled, 8 were excluded; 1 for
      inadequate documentation, 5 for protocol violation, and 2 for positive IVT of the
      uninjured ankle. Of the 97 patients analyzed, 13 had fractures identified by
      radiography, including 9 lateral malleolar, 1 medial malleolar, 1 bimalleolar,
      and 2 talar fractures. Only 5 of the 13 fractures were detected with IVT
      (sensitivity = 39%; 95% CI: 14-68%). Seventy of 84 nonfractured ankles had
      negative IVT (specificity = 83%; 95% CI: 74-91%). Of the 19 with positive IVT, 5
      had fractures (positive predictive value of 26%; 95% CI: 9-51%). Of the 78 with
      negative IVT, 70 had no fracture (negative predictive value of 90%; 95% CI: 81
      96%). Overall, 75 of 97 IVTs were correct (77%), most of which were among
      patients without fractures.

PMID- 8870758
TI  - Management of nontraumatic subarachnoid hemorrhage in a patient with sickle-cell
      disease: a case report.
AB  - Subarachnoid hemorrhage (SAH) due to sickle-cell anemia is rare, but potentially
      devastating. However, with early recognition of SAH, aggressive support with
      exchange transfusion, cerebral angiography, and neurosurgical intervention, a
      positive outcome may be achieved. A case report of SAH managed in this fashion is
      reported. Based on similar cases in the literature, a suggested treatment
      protocol is provided for the management of nontraumatic SAH in sickle-cell
      patients presenting to the ED.

PMID- 8870759
TI  - Raeder's paratrigeminal syndrome: a case report.
AB  - Raeder's paratrigeminal syndrome is an uncommon neurologic disorder characterized
      by oculosympathetic paralysis, including ptosis and miosis. In the ED, this
      syndrome can be easily confused with Horner's syndrome, although with Raeder's
      syndrome trigeninal nerve irritation and preservation of facial sweating are
      noted. This report reviews a case of a 62-year-old man who presented to the ED
      with signs and symptoms consistent with Raeder's syndrome. MRI with angiography
      revealed a carotid artery dissection, and the patient was admitted and
      anticoagulated. The syndrome has been associated with head trauma, hypertension,
      vasculitis, migraine headaches, parasellar mass lesions, and internal carotid
      artery dissections. Hence, treatment of the patient who has Raeder's syndrome is
      dependent on the specific underlying lesion.

PMID- 8870760
TI  - Systemic toxicity from ocular homatropine.
AB  - Toxidromes are well known to emergency physicians. An unclear or incomplete
      history and subtle findings on physical examination make the diagnosis of
      poisonings challenging. This article reports a patient who had an acute onset of
      visual hallucinations, pressured speech, and mania. Although she denied taking
      any medications, she was ultimately diagnosed as having anticholinergic toxicity.
      On further questioning of family members, it was discovered that she was being
      treated for anterior uveitis with 5% homatropine. This case illustrates the
      potential role of ocular medications in systemic toxicity. Patients often do not
      consider eyedrops to be medications, and their use may be overlooked in the
      medical history. It also is important to educate patients and medical staff in
      methods to minimize systemic toxicity when using ocular medication.

PMID- 8870761
TI  - Emergency medicine journal clubs.
AB  - OBJECTIVE: To ascertain the status of journal club within emergency medicine (EM)
      residency programs and to describe 3 currently used formats. METHODS: The
      directors of U.S. Residency Review Committee for Emergency Medicine (RRC-EM)
      approved residency programs were surveyed to determine the features of their
      programs' journal clubs. Responses to 3 questions assessing the degree of
      satisfaction (5-item scales from very good to very poor) with the "current
      format," "resident participation," and "faculty participation" from the survey
      were grouped according to the program director's impressions of resident and
      faculty "enjoyment" (2 3-item scales) and whether the journal club is a "success"
      (3-item scale) to develop an overall satisfaction index. Three journal club
      formats currently in use at EM residencies are described in detail. RESULTS: Of
      the 101 directors surveyed, 91 (90%) responded. The respondents' overall
      satisfaction index was highest when the journal club was held in the evening (p <
      0.008) or at a faculty member's home (p < 0.0004). The format of the journal club
      (e.g., by topic, with a statistical focus, with a research design, focus, or as a
      clinical practice update) was not associated with the overall satisfaction index.
      CONCLUSION: Journal clubs associated with EM residencies vary in format and
      perceived success. The 3 representative journal clubs illustrate different format
      options.

PMID- 8870762
TI  - Clinical pearls. Headache and eye pain.

PMID- 8870763
TI  - Thrombolytic therapy for cerebral infarction.
AB  - Until recently, no clinically effective therapy for acute ischemic stroke has
      been available. Recent advances in the use of thrombolytic therapy for ischemic
      stroke appear promising in clinical care. As the use of thrombolytic therapy in
      acute stroke progress, emergency physicians (EPs) will become increasingly
      involved in its implementation. The EP must be cognizant of both prior and
      ongoing investigations in acute ischemic stroke therapy. To that end, this
      article reviews research in the field of thrombolytic therapy for acute ischemic
      stroke.

PMID- 8870764
TI  - Statistical methodology: I. Incorporating the prevalence of disease into the
      sample size calculation for sensitivity and specificity.
AB  - Careful consideration of statistical issues related to the choice of a sample
      size is critical for achieving meaningful results in research studies designed to
      evaluate diagnostic tests. When assessing the ability of a diagnostic test to
      screen for disease, the parameters sensitivity, specificity, and predictive
      values are of interest. Study sample size requirements can be calculated based on
      a clinically acceptable degree of precision, the hypothesized values of
      sensitivity and specificity, and the estimated prevalence of disease in the
      target population. The simple methods and tables in this paper guide the
      researcher when deciding how many subjects to sample in a study designed to
      estimate both the sensitivity and the specificity of a diagnostic test, given a
      specified precision and estimated disease prevalence.

PMID- 8870765
TI  - Getting the round tube in the round hole in the field.

PMID- 8870766
TI  - Feasibility of routine screening of patients for alcohol abuse.

PMID- 8870767
TI  - Complete heart block or not.

PMID- 8870768
TI  - Scaling of relative velocity between vehicles.
AB  - Data are presented on the ability of drivers to perceive and scale the relative
      velocity between their own and a lead vehicle. Experiments were carried out on
      four groups of subjects using Ekman's ratio-rating method. Only when the
      subtended angular velocity of the lead vehicle exceeded about 0.003 rad/s were
      the subjects able to scale the relative velocity. The threshold subtended angular
      velocity obtained in the experiments was very much affected by the ability of
      subjects to use the concept of a ratio-engineering students found this a simpler
      task than did subjects from the general population. The result of this was that
      the values used by engineering students were closer to the real values. The
      relative velocity was perceived non-linearly, with a Stevens' power law exponent
      of about 0.8. It was found that linear models gave as good a fit to the data. The
      implications of the results of the experiments are (i) traffic flow models that
      include human visual characteristics must consider the "dead zones" in response
      produced by thresholds of subtended angle change subtended angular velocity; (ii)
      it may be necessary to consider the non-linear relationship between perceived
      relative velocity and actual relative velocity; (iii) in overtaking, the driver
      will not be able to scale the speed of the oncoming vehicle as the subtended
      angular velocity will be below the threshold value at the time of making the
      decision to overtake.

PMID- 8870769
TI  - Safety-belt effectiveness: the influence of crash severity and selective
      recruitment.
AB  - While theoretical considerations show that the effectiveness of occupant
      protection devices declines from 100% at very low crash severity to 0% at high
      severity, empirical details have been lacking. When overall in-use effectiveness
      is estimated by applying traditional methods to data sets that lack a measure of
      severity, large biases are introduced because non-wearing drivers are riskier
      drivers, an effect that has been called selective recruitment. These effects are
      investigated empirically using National Accident Sampling System (NASS) data in
      which crash severity is measured by delta-v, the estimated change in the speed of
      the car as a result of the crash. Supplemental results are obtained using
      published police-reported data containing a more easily obtained but less
      objective severity measure. Both data sets provide information on driver
      fatalities and injuries, thus allowing four comparisons of effectiveness
      estimates based only on total casualties with ones taking into account the
      different severities of crashes by belted and unbelted drivers. The data show
      consistently that the probability that a driver is belted declines as crash
      severity increases. Belt effectiveness estimates ignoring this effect are biased
      upwards by large amounts (for example, 60% compared to 40% for injuries using
      NASS data). Belts appear more effective at preventing fatalities than at
      preventing injuries. The results are consistent with a prior estimate, derived
      using a method unaffected by the biases discussed here, which found that,
      averaged over all crashes, safety belts reduce driver fatality risk by (42 +/-
      4).

PMID- 8870770
TI  - The validity of police assessment of driver intoxication in motor vehicle crashes
      leading to hospitalization.
AB  - We evaluated the accuracy of the field sobriety assessment of police officers
      following a motor vehicle crash. Using linked data from a statewide traffic crash
      database and the trauma center registry, the results of a field sobriety
      evaluation for each driver were compared with a blood alcohol concentration (BAC)
      drawn in the emergency department. BAC values served as the "gold standard" in
      which drivers with values over 0.1 mg/dl were classified as intoxicated. The
      subjects were drivers over age 15 years who were admitted or died at Level I
      trauma center as a results of motor vehicle crash injuries during 1986-1993. A
      total of 1336 subjects had both a recorded BAC and a police sobriety assessment.
      Seventy percent of subjects were male and 79% under the age of 35 years. Overall,
      40% of all subjects were judged by police to have been impaired, based on the
      scene sobriety assessment. Among all drivers, the field assessment had a
      sensitivity of 91%, a specificity of 90% and a predictive value positive of 85%.
      After excluding the 419 drivers which had breath testing as part of their
      assessment, the field assessment had a sensitivity of 74% and a specificity of
      97%. The sensitivity of the field assessment did not vary appreciably by gender
      but was lower among older drivers, and higher among severely injured drivers and
      those involved in weekend and nighttime crashes. Police officers in this sample
      appear to recognize drunk driving with a high degree of accuracy when
      investigating crashes in which the driver is transported to a trauma center.

PMID- 8870771
TI  - The public health impact of minor injury.
AB  - The mortality and hospital morbidity data usually used to quantify the burden of
      injury are generally considered to represent only the tip of the iceberg. This
      article documents the population-based morbidity arising from non-hospitalised
      injuries and demonstrates the public health importance of this group of injuries.
      A prospective cohort study was conducted in an Australian population using a
      sample of injured adults to identify the health outcomes arising from the range
      of injuries. The total health loss caused by injury experienced by these subjects
      over the period of injury recovery was calculated and then weighted to provide
      population estimates. This study has shown that minor injuries are responsible
      for the greater part of the injury-related health burden in the adult community.
      Injuries that can be coded as 1 on the Abbreviated Injury Scale account for 80%
      of the morbidity arising over the first six months after injury and about 75% of
      the estimated lifetime morbidity. The lifetime estimates of morbidity resulting
      from injuries not considered serious enough to admit to hospital were of an order
      of magnitude higher than those that resulted in either death or hospitalisation.
      Sprains contributed as much to the total morbidity as all other injuries types
      combined and limb injuries contributed more to the total morbidity than injuries
      to the more central structures. The results of this study provide a strong
      argument for the recognition of the public health importance of minor injury.
      Strategies for the prevention and management of minor injury must be included in
      national programmes for injury control.

PMID- 8870772
TI  - Medications as risk factors for farm injury.
AB  - A case-control study was used to determine whether cases of farm injury were more
      likely than controls to have been regularly exposed to certain types of
      medication including those that cause side effects which may predispose to
      injury. Persons reporting an injury (n = 176) were identified in a population
      based mail survey of people on 1364 Ontario farms, and compared to people without
      injuries using a 4:1 control: case ratio. Bivariate, stratified, and
      multivariable analyses were used to quantify the strength of associations between
      exposures to certain medications and the occurrence of farm injury. Those who
      regularly used certain types of medication were separated into two groups: people
      who used the medications in isolation, and those who used the medications in
      combination with other medications. Response to the survey was 77.3% among cases
      and 82.6% among controls. Strong and statistically significant increases in risk
      for injury were observed in association with the regular use of stomach remedies
      or laxatives by males (OR 2.8; 95% CI: 1.0,7.7), and regular use of heart of
      circulatory medications by men over the age of 45 (OR 4.2; 95% CI: 1.2,14.7). The
      identified associations remained after adjustment for age, co-morbidity, tillable
      farm acreage, education, income, alcohol consumption and tobacco use. Several
      possible explanations for the occurrence of the identified associations, other
      than the etiological hypothesis originally advanced, are discussed.

PMID- 8870773
TI  - Head injuries and bicycle helmet laws.
AB  - The first year of the mandatory bicycle helmet laws in Australia saw increased
      helmet wearing from 31% to 75% of cyclists in Victoria and from 31% of children
      and 26% of adults in New South Wales (NSW) to 76% and 85%. However, the two major
      surveys using matched before and after samples in Melbourne (Finch et al. 1993;
      Report No. 45, Monash Univ. Accident Research Centre) and throughout NSW (Smith
      and Milthorpe 1993; Roads and Traffic Authority) observed reductions in numbers
      of child cyclists 15 and 2.2 times greater than the increase in numbers of
      children wearing helmets. This suggests the greatest effect of the helmet law was
      not to encourage cyclists to wear helmets, but to discourage cycling. In
      contrast, despite increases to at least 75% helmet wearing, the proportion of
      head injuries in cyclists admitted or treated at hospital declined by an average
      of only 13%. The percentage of cyclists with head injuries after collisions with
      motor vehicles in Victoria declined by more, but the proportion of head injured
      pedestrians also declined; the two followed a very similar trend. These trends
      may have been caused by major road safety initiatives introduced at the same time
      as the helmet law and directed at both speeding and drink-driving. The
      initiatives seem to have been remarkably effective in reducing road trauma for
      all road users, perhaps affecting the proportions of victims suffering head
      injuries as well as total injuries. The benefits of cycling, even without a
      helmet, have been estimated to outweigh the hazards by a factor of 20 to 1
      (Hillman 1993. Cycle helmets-the case for and against. Policy Studies Institute,
      London). Consequently, a helmet law, whose most notable effect was to reduce
      cycling, may have generated a net loss of health benefits to the nation. Despite
      the risk of dying from head injury per hour being similar for unhelmeted cyclists
      and motor vehicle occupants, cyclists alone have been required to wear head
      protection. Helmets for motor vehicle occupants are now being marketed and a
      mandatory helmet law for these road users has the potential to save 17 times as
      many people from death by head injury as a helmet law for cyclists without the
      adverse effects of discouraging a healthy and pollution free mode of transport.

PMID- 8870774
TI  - Behavioural feedback to risk variation ensues from unsatisfied appetency.
AB  - For a long time, but particularly since the last two decades, the phenomenon of
      behavioural feedback to risk variation, especially to highway safety measures,
      has been the subject of numerous papers and debates. It has been advanced that
      human behaviour ensues from the interaction between two motivational systems: (1)
      appetency, governed by a homeostasic mechanism, wherein the individual seeks to
      satisfy needs, and (2) aversion, guided by the principle of zero aversion,
      whereby the individual seeks to avoid aversive stimuli. When an individual
      considers the possibility of undertaking an action, he weighs the advantages
      (appetency) and the disavantages (aversion). If the appetency proves to be
      stronger than the aversion, the action is completed and ipso facto, the
      individual accepts the risk associated with it. In this article, it is suggested
      that the behavioural feedback following a variation in the risk (aversion) ensues
      from unsatisfied appetency. If the unsatisfied appetency is nil (the individual
      is already satisfied), a drop in the aversive constraint (e.g. lowered risk of an
      accident) will not cause any behavioural feedback. On the other hand, if there is
      an unsatisfied appetency (the individual is not fully satisfied), a drop in the
      aversive constraint will bring about behavioural feedback in proportion to the
      level of unsatisfied appetency. Cases in which behavioural feedback is likely to
      arise and the implications for public policy-making are briefly discussed.

PMID- 8870775
TI  - Impact of the Illinois child passenger protection act: a retrospective look.
AB  - This paper considers the Illinois child restraint use law which took effect in
      July 1983. This law requires parents to use safety seats for children under age
      4, and seat belts or safety seats for those aged 4 or 5. ARIMA time series models
      and a monthly data set of fatalities and injuries from 1980 through 1986 were
      utilized. The law reduced the total number of children under 5 killed or injured
      in traffic crashes by 10% along with a 17% decline in the number of child
      injuries per crash. No spillover effect was found for older children.

PMID- 8870776
TI  - Influences of the physical parameters on the risk to neck injuries in low impact
      speed rear-end collisions.
AB  - The current state of neck injuries sustained in car-to-car rear-end collisions
      were investigated according to recent automobile accident statistical data in
      Japan. To clarify the neck injury mechanisms for low impact speed car collisions,
      the newly developed impact sled experiment which simulates actual car impact
      acceleration was performed using human subjects. In order to measure and analyze
      the physical parameters such as human head rotational acceleration, neck bending
      moment, shearing and axial forces, the component measurement method with six
      degrees of freedom was applied and demonstrated. Furthermore, relationships among
      the physical parameters, impact speeds, sitting positions, headrest heights and
      neck muscle tones applied on the subject's head and neck system were analyzed.
      These analyses would enable us to comprehend the conditions of the neck muscle
      tone and the effects of the sitting postures including headrest height, factors
      which are of vital importance to the understanding of neck injury mechanisms.

PMID- 8870777
TI  - A multiple discriminant analysis of vessel accidents.
AB  - A large sample of 936 vessel accident cases occurring between 1979 and 1987 on
      the lower Mississippi River were cluster analyzed to generate four groups
      relatively unique in their respective attribute values. The attributes used to
      cluster the accidents included participation in the U.S. Coast Guard's New
      Orleans Vessel Traffic Service (NOLA-VTS), type of accident, river stage traffic
      level, system utilization, accident location, weather conditions, and time of
      accident. The four-group cluster solution resulted in logical groupings, given
      the realities of navigating the lower Mississippi River. The four groups
      resulting from the cluster analysis were characterized as Group 1: Danger Zone
      (224 cases), 100% NOLA-VTS participants whose accidents occurred primarily on the
      most dangerous part of the river; Group 2: Bad Conditions for Good Navigators
      (230 cases), characterized by a high rate of participation and unserious
      accidents occurring in treacherous navigating conditions; Group 3: Probably
      Preventable (134 cases), characterized by a low participation rates and serious
      accidents occurring in not the worst navigating conditions; and Group 4:
      Accidents That Should Not Have Happened (345 cases), characterized by zero
      participation and serious accidents occurring in reasonable navigating
      conditions. Significant marginal participation rates for the marine tracking
      technology across the four accident clusters (100% for Group 1, 67% for Group 2,
      37% for Group 3, and 0% for Group 4) effectively distinguishes between casualty
      groups. In the subsequent discriminant analysis, three discriminant functions
      correctly classified 96% of the total accidents, including 100% of Group 1 and
      Group 4, 90% of Group 2, and 88% of Group 3. The variables contributing most to
      overall group differentiation were participation in the system, overall system
      utilization, river stage, traffic level, time and location of accidents. The
      three discriminant functions were statistically significant, with each individual
      function accounting for a large relative percentage of the variance between the
      groups. In order of decreasing discriminating power, the functions could be
      characterized as (1) System Participation and Utilization, (2) Navigating
      Conditions, and (3) Time and Place.

PMID- 8870778
TI  - The scope and nature of the drowsy driving problem in New York State.
AB  - A telephone survey was conducted of a random sample of New York State licensed
      drivers to determine the prevalence and circumstances of drowsy driving. Based on
      the survey responses, 54.6% of the drivers had driven while drowsy within the
      past year; 22.6% had ever fallen asleep at the wheel without having a crash, 2.8%
      had ever crashed when they fell asleep, and 1.9% had crashed when driving while
      drowsy. Of the reported crashes due to driving while drowsy or falling asleep at
      the wheel, 82.5% involved the driver alone in the vehicle, 60.0% occurred between
      11:00 p.m. and 7:00 a.m. 47.5% were drive-off-road crashes, and 40.0% occurred on
      a highway or expressway. Multiple regression analysis suggested that the
      following driver variables are predictive of an increased frequency of driving
      drowsy: demographic characteristics (younger drivers, more education, and men);
      sleep patterns (fewer hours of sleep at night and greater frequency of trouble
      staying awake during the day); work patterns (greater frequency of driving for
      job and working rotating shifts); and driving patterns (greater number of miles
      driven annually and fewer number of hours a person can drive before becoming
      drowsy).

PMID- 8870779
TI  - Does license disqualification reduce reoffence rates?
AB  - A review was conducted of the subsequent driving records of over 25,000
      Queensland drivers cited for a drink driving offence in 1988 who received at
      least one subsequent license restriction. The interval of follow-up was at least
      3 years, average 3.9 years. Periods of driving disqualification were identified
      and, for each driver, the total amount of time during restricted and unrestricted
      driving was computed; the numbers of events, i.e. crashes and traffic offences,
      recorded during these periods were counted. Rates under disqualification and
      during legal driving, expressed per thousand person-years were derived by
      dividing total numbers of events by total time during which they could occur.
      Three categories of traffic violation were considered: drink driving offences;
      traffic offences unassociated with drink driving, and any offence involving
      driving. Since only 12% of the offenders and 9% of the reoffenders were female,
      detailed analyses are presented for men only; results for women were little
      different. Statistical inference assumed a Poisson model for crashes and a
      negative binomial model for offences, and analyses were performed after
      stratification by number of drink driving offences. Calculated rates during
      periods of disqualification were about one third of the rates during legal
      driving for crashes and all three categories of traffic offence, ranging from 25%
      in the case of unassociated offences to 35% for any driving offence. There were
      differences, some statistically significant, by age and between metropolitan,
      provincial city and rural regions of the State, but most were relatively minor.
      Drivers were apprehended more frequently earlier in the disqualification period
      than later. It is impossible from these data to distinguish between reduced
      driving levels and more cautious traffic behaviour during periods of license
      restriction. It is nonetheless clear that while such penalties are in operation,
      they substantially reduce the negative impact of convicted drink-drivers on the
      road. Unfortunately the data do not permit one to say whether or for how long the
      effect persists.

PMID- 8870780
TI  - Protection of the side of the head.
AB  - The side of the head is a frequent impact site for pedal cyclists, motorcyclists,
      and industrial workers. It is vulnerable to impact, yet many helmet standards do
      not have impact tests at the side of the helmet. Laboratory impact tests should
      reproduce the phenomena in real impacts, but usually they do not allow the
      headform to rotate, or ignore the effect of the neck on the motion of the head.
      The authors designed a linkage, simulating the flexibility of the neck, for use
      with anthropomorphic dummies in helmet testing. Impacts at the side of the
      helmet, normal to the helmet surface, were made with flat and hemispherical
      strikers. Head rotation during impacts caused the impact site to move, in some
      cases to below the level protected by the helmet. The peak angular head
      acceleration correlated with the peak linear accelerations. Neck flexibility
      means that helmets can protect the head from higher kinetic energy impacts than
      those specified in standards using immovable headforms or impact anvils. The load
      spreading efficiency of polypropylene foam, used in soft shell bicycle helmets,
      is better than that of polystyrene foam. The authors conclude that the side of
      the head can be protected by a suitable helmet design.

PMID- 8870781
TI  - Exploring the male-female discrepancy in death rates from bicycling injury: the
      decomposition method.
AB  - The population-based death rate as an important indicator of health status has
      been widely used in injury research. Generally, the death rate from injury for
      males is about three times that for females. The importance of the various
      factors that contribute to this male-female discrepancy, however, has not been
      well understood. Using the innovative Decomposition Method, data from the
      Nationwide Personal Transportation Survey, the National Electronic Injury
      Surveillance System, and the National Center for Health Statistics were analyzed
      to explore the determinants of the male-female difference in death rates from
      bicycling injury. The results revealed that males have higher death rate from
      bicycling injury than females because they have a greater exposure rate and case
      fatality rate. When exposure measured by number of bicycle trips is taken into
      account, males are at slightly lower risk of injury than females. The relative
      contribution of case fatality, exposure, and risk to the 6.4-fold difference in
      death rates from bicycling injury between men and women is 53%, 51%, and -4%,
      respectively.

PMID- 8870782
TI  - Comment on Theeuwes and Riemersma's revisit of daytime running lights.

PMID- 8870783
TI  - Preference of invasive cytotrophoblast for maternal vessels in early implantation
      in the macaque.
AB  - The interaction of cytotrophoblast with maternal endometrium, especially
      endometrial blood vessels, was examined in macaque gestational stages between 2
      and 8 days after the onset of implantation. Serial sectioning of these early
      implantation sites allowed immunostaining of consecutive sections with a number
      of different antibodies, facilitating cell identification. In the earliest
      implantation site, immunostaining showed that antibody to cytokeratin stained
      cytotrophoblast, syncytial trophoblast, epithelial plaque and endometrial gland
      cells. However, only those cytotrophoblast cells near the maternal-fetal border
      and within vessels showed surface staining for neural cell adhesion molecules and
      only syncytial trophoblast showed SP1 reactivity. Even at this early stage
      cytotrophoblast filled the lumen of superficial arterioles, whereas dilated
      venules contained only a few cytotrophoblast cells. In later stages endovascular
      cytotrophoblast not only plugged many spiral arterioles but also migrated into
      the walls of these arterioles, and progressed into deeper coils. Displacement of
      endothelial cells and disruption of vessel walls were illustrated with antibody
      to factor VIII, TGF alpha, and desmin. Clusters of cytotrophoblast cells at the
      fetal-maternal interface tended to bypass clusters of epithelial plaque cells and
      larger clusters of maternal fibroblasts, but readily entered all vascular spaces.
      Consequently the vascular system constituted a major pathway of invasion,
      although the arterioles were the only component substantially invaded beyond the
      trophoblastic-shell/endometrial border.

PMID- 8870784
TI  - Ontogeny of the rat bladder: smooth muscle and epithelial differentiation.
AB  - The sequential expression of smooth muscle and epithelial markers in the rat
      bladder has been defined. Smooth muscle differentiation, based on cell morphology
      and immunohistochemical localization of smooth muscle alpha-actin, myosin,
      vinculin, desmin, vimentin and laminin, begins at 16 days of gestation (birth =
      22 days) in the rat bladder. Smooth muscle cell differentiation begins in the
      periphery of the bladder mesenchyme immediately subadjacent to the serosa and
      continues toward the urothelium. The cytokeratins 5, 7, 8, 14, 18, and 19 are
      expressed in the bladder epithelium as a function of developmental age with
      cytokeratin 7, 8, 18, and 19 being coexpressed at 15 days' gestation followed by
      cytokeratin 5 at 17 days' gestation and cytokeratin 14 in the newborn bladder. An
      understanding of the ontogeny of both smooth muscle and epithelial
      differentiation markers in the normal bladder will allow us to study events that
      occur in the diseased bladder.

PMID- 8870786
TI  - Axotomy induces retraction of the dendritic arbor of adult rat rubrospinal
      neurons.
AB  - The effect of distal axonal injury on the soma-dendritic morphology of intrinsic
      central neurons was examined using adult rat lumbar spinal cord-projecting
      rubrospinal neurons as a model. The soma-dendritic morphology was revealed using
      an improved Golgi-aldehyde method. Impregnated neurons were reconstructed in the
      two-dimensional plane for analysis. Four weeks after axotomy, neurons had reduced
      soma sizes and remained multipolar in shape. Some dendrites were found to end not
      far from their cell bodies. In addition, no long dendrite was identified
      following axotomy. Sholl's analysis [The Organization of the Cerebral Cortex.
      London, Methuen, [1956] revealed that axotomized neurons had fewer dendritic
      branches than control neurons. Total dendritic length was also reduced.
      Subsequent analyses showed that the average number of dendritic trunks was not
      altered however the mean number of terminal branches per dendritic trunk was
      reduced. The dendritic membrane of the normal neurons was usually smooth with
      occasional short protuberances on the proximal dendrites and spines on the distal
      dendrites, which did not change after axotomy. In control neurons, we identified
      an elaborate type of dendritic structure named dendritic appendage aggregates.
      These aggregates were located preferentially on terminal dendrites and were
      classified into three categories according to their complexity. The incidence of
      occurrence for these aggregates decreased following distal axotomy. These
      phenomena indicate that rat lumbar spinal cord-projecting rubrospinal neurons
      retract their distal dendrites in response to distal axotomy. The observed
      anatomic restructuring following axonal injury is likely to be accompanied by an
      alteration of afferents which normally synapse on distal dendrites.

PMID- 8870785
TI  - Effects of orchiectomy on the rat parotid gland--an ultrastructural and
      stereological study.
AB  - The relation of the tests/testosterone with the structure and function of the
      mammalian parotid gland has so far been poorly investigated. The present study
      deals with the morphology of the rat parotid gland and its changes after
      orchiectomy and testosterone substitution. The glands of control and experimental
      animals (orchiectomized and orchiectomized with testosterone substitution) were
      analyzed by electron microscopy and stereology. In orchiectomized animals 30-60
      days after castration, a significant reduction of the volume of the acini and the
      duct system as well as a significant increase of the connective tissue volume per
      cubic millimeter of the gland were noted. The volume and length of the
      intercalated and the striated ducts per cubic millimeter of parotid tissue are
      significantly reduced 45-60 days after orchiectomy. Excretory ducts seem to be
      unaffected by orchiectomy. The structure of the rat parotid acini is also changed
      by castration, indicating a reduction of acinar-cell activity. In controls, the
      volume of acinar cells with wide cisternae of rough endoplasmic reticulum is 3
      times larger than the volume of acinar cells with regular and narrow cisternae of
      rough endoplasmic reticulum. After orchiectomy, the volume of acinar cells with
      wide cisternae of rough endoplasmic reticulum is significantly decreased, while
      the volume of acinar cells with regular and narrow cisternae of rough endoplasmic
      reticulum is significantly increased. Exogenously given testosterone can prevent
      or alleviate the mentioned effects of orchiectomy on the gland. It is concluded
      that orchiectomy affects the rat parotid gland, demonstrating the existence of an
      interaction between the testis and the mammalian parotid gland.

PMID- 8870787
TI  - Populations of myelinated nerve fibers in the C8 and L4 ventral and dorsal roots
      in the opossum, Monodelphis domestica.
AB  - A quantitative light-microscopic analysis of the ventral and dorsal roots at the
      C8 and L4 segments of the spinal cord was made in the opossum, Monodelphis
      domestica, to evaluate the number of myelinated fibers and their class
      distribution, and will serve as a baseline to a study of myelinogenesis in that
      species. In male opossums, the C8 ventral root comprises an average of 595
      myelinated fibers (70.3% alpha: 29.7% gamma) and the dorsal root 1,124 fibers
      (29.4% type I: 41.2% type II: 29.4% type III). The L4 ventral root has an average
      of 831 fibers (57.9% alpha: 42.1% gamma), and the dorsal root 2,079 fibers (17.4%
      type I:44.7 type II: 37.9% type III). The females have less fibers but their size
      and class proportions are comparable to those of the males. These data are
      discussed in relation to peripheral innervation and are compared to those
      reported for the rat and the cat.

PMID- 8870788
TI  - Effects of masticatory muscle function on bone mass in the mandible of the
      growing rat.
AB  - The effect of altered masticatory muscle function on bone mass at different sites
      in the rat mandible was studied using aluminium as a reference substance in
      computer-assisted image analysis. Forty-two growing male rats were divided into
      three groups, of which one group was killed at the beginning of the experiment to
      provide baseline values. Of the remaining two, one received a hard diet (control
      group) and the other a soft diet. After 28 days the rats were killed and the
      mandibles were excised. Lateral radiographs were taken of the mandible halves
      together with an aluminium stepwedge and then analysed by an image analysis
      system. Radiographic bone mass was measured in the transverse plane as "aluminium
      equivalent thickness' in millimetres. Standardized areas were chosen to
      investigate regions with different functional demands. Significant differences
      were found between the groups in the alveolar bone of the molars and the incisor,
      as well as in the condylar costa and the condylar process. Significant
      differences were also found in some areas related to muscle insertion, such as
      the anterior lower border of the ramus, whereas no statistically significant
      differences could be found in others, such as the posterior lower border of the
      angular process. In conclusion, altered masticatory function influences the
      amount of bone mass in certain parts of mandible, where changes in applied
      bending forces have possibly altered the bone strain.

PMID- 8870789
TI  - Skeletal maturation of wrist and hand ossification centers in normal Spanish boys
      and girls: a study using the Greulich-Pyle method.
AB  - The skeletal maturation of the upper limb distal segment was studied in 239
      Spanish boys and girls between birth and 14 years of age. The atlas of Greulich
      and Pyle, offering standards of skeletal development of white North American
      children, was used as reference. The results obtained show firstly that in
      absolute terms, the ossification process is earlier in girls than in boys. This
      difference is maximum between 5 and 11 years of age. The boys show a delay of
      around 3 months with respect to their North American opposites. The girls, in
      contrast, show a better fit to the corresponding (female) standard of the atlas.
      In general, the highest agreement between bone age and chronologic age is for the
      ossification centers of the distal epiphysis of the ulna and radius and for those
      of the metacarpal bones. At the level of the carpus, individual analysis of the
      ossification centers shows that the capitate and hamate bones in the girls evolve
      most in accord with chronologic age. At the other extreme, and in both sexes, the
      ossification centers of the trapezium and trapezoid bones are statistically
      furthest from chronologic age.

PMID- 8870790
TI  - Variations of the pubic vascular anastomoses in black South Africans.
AB  - Variations of the arterial and venous pubic anastomoses (APA, VPA) were studied.
      Forty-four percent of the APA were replaced by an obturator artery arising from
      the inferior epigastric and 25% by an obturator artery arising from the external
      iliac. Seven percent of the VPA were replaced by a single obturator vein, 37% by
      the superior companion of a double obturator vein, and 2% by a double obturator
      vein. Black South African subjects exhibit a higher incidence of variations of
      the pubic anastomoses than North American, European and Japanese populations.

PMID- 8870791
TI  - Musculus sartorius bicaudatus.
AB  - While dissecting 88 lower limbs, a distal division of the sartorius muscle was
      detected in one of the specimens. The larger posteromedial portion was found to
      take a normal course to the so-called superficial pes anserinus. The thinner
      anterolateral portion attached to the medial meniscus anteromedially. The smaller
      anterolateral part approached the medial meniscus anteromedially, pushing the
      synovial membrane into the joint. Its meniscal attachment ensures that the medial
      meniscus is stabilized in its primary position during bending and external
      rotation in the knee joint, thus preventing its herniation or injury during
      sudden extension. The accessory part of the sartorius muscle thus acts as a
      protector of the medial meniscus.

PMID- 8870792
TI  - Possible glial contribution of rat hippocampus lactate as assessed with
      microdialysis and stress.
AB  - Microdialysis for the continuous monitoring of lactate ("lactography") was
      applied in rat brain hippocampus in an attempt to establish whether lactate is of
      neuronal or glial origin. Lactate was analyzed with an electrochemical assay
      after enzymatic oxidation in dialysates derived from a short-term (1 or 2 days
      after implantation of the probe) and a long-term (14 or 15 days) preparation. In
      the short-term experiment the lactate levels in the dialysate were higher without
      glucose in the perfusate, whereas in the long-term experiment a several fold
      increase in lactate was observed in the presence of 5 mM glucose. During stress,
      increases in lactate were virtually similar both in the acute (with or without
      glucose in the perfusate) and in the chronic preparation (response in the
      presence of glucose only). In the long-term preparation presence of reactive
      astroglia cells was visualized immunohistochemically with antibodies against
      glial fibrillary acidic protein. Damage of the hippocampus and the corpus
      callosum was seen in the chronic preparation with silver impregnation staining.
      These results emphasize the importance of the presence of glucose in the
      perfusate and they are consistent with the idea that glial cells contribute to
      extracellular lactate in the rat hippocampus in vivo and that stress activates
      the astroglial glycogen pool.

PMID- 8870793
TI  - Application of glutamate in the cortex of rats: a microdialysis study.
AB  - Glutamate, a major neurotransmitter in the brain, is also involved in
      pathophysiological processes resulting in secondary lesions following ischaemia
      or trauma. In the present study we investigated the relationship between
      glutamate excitotoxicity free radical induction (indicated by ascorbic acid
      level) and glucose-lactate metabolism. Monosodium glutamate was applied through
      microdialysis probes (500 mM in perfusate) into the cortex of rats for 30 minutes
      and ascorbic acid (ASC), glucose (GLUC) and lactate (LAC) were measured in
      dialysates. Glutamate produced a cortical lesion with an average volume of 12.7
      +/- 1.4 mm3. Analysis of dialysates revealed a significant increase of ASC (325
      +/- 52% of baseline) and LAC (677 +/- 86%) in the core lesion. In the lesion
      periphery a non-significant and short-lasting elevation was measured for both
      parameters with a second microdialysis probe (about 1.3 mm frontally to the first
      probe). A concomitant decrease of GLUC was found in both probes, reaching 29 +/-
      8% and 60 +/- 7% of basal levels in the core and periphery of the lesion,
      respectively. In addition, we studied the delivery characteristics of several
      glutamate concentrations (10, 100 or 1000 mM in perfusate) during a 90-minute
      application into the cortex. The delivery of glutamate from the perfusate to the
      brain was about 33-38% in the first 30 min and afterwards 11 25% of the total in
      the perfusate. The results show that cortical application of glutamate changes
      the composition of the extracellular fluid, which could contribute to the
      development of the lesion.

PMID- 8870794
TI  - Clinical microdialysis: the role of on-line measurement and quantitative
      microdialysis.
AB  - The use of microdialysis in the clinic is examined in the light of lessons learnt
      from microdialysis in freely moving rats. Changes in concentrations of
      metabolites are an important index of the state of health of tissues. For
      effective therapeutic intervention rapid assays are essential Enzyme-based on
      line assays for glucose and lactate are described. By combining two of these
      assays simultaneous measurements of glucose and lactate, sampled at 2 min
      intervals can be obtained. The relation between dialysate concentrations and the
      true extracellular concentration of an analyte is dependent on conditions in the
      tissue sampled and cannot be calculated from in vitro probe recoveries.
      Furthermore, with acute implantation of the probe and possibly rapidly changing
      tissue conditions, there will be changes in probe recovery in vivo. Quantitative
      microdialysis allows the measurement of the true extracellular concentration and
      the probe recovery in vivo. The clinical applicability of a number of
      quantitative microdialysis methods is discussed, and three approaches
      highlighted. By increasing membrane length and reducing flow rate recovery in
      vivo can be increased to 100%. In this case dialysate concentrations equal
      extracellular ones. By perfusing an inert exogenous compound an index of changes
      to extracellular volume and hence tissue oedema can be obtained. In the zero net
      flux method the infusion of a few concentrations of the analyte under study
      allows the direct determination of both the ECF concentration and the in vivo
      recovery. The latter can provide valuable information about changes in the
      physical as well as chemical state of the tissue. This can guide rapid effective
      therapeutic intervention.

PMID- 8870795
TI  - Intracerebral microdialysis markedly inhibits the propagation of cortical
      spreading depression.
AB  - It is accepted that the ionic composition of the medium perfused through a
      microdialysis probe should match that of the extracellular fluid (ECF) under
      physiological conditions. In contrast, the possibility that control artificial
      cerebrospinal fluid may influence the experimental or pathological conditions
      under study, by buffering changes in the ECF composition, has been neglected.
      Spreading depression (SD) is a propagating transient suppression of electrical
      activity due to cellular depolarization which may contribute to neuronal damage
      in focal ischaemia, and underlie the migraine aura Here we report that
      microdialysis markedly inhibits SD propagation, by buffering the sudden increase
      in extracellular K+ associated with this event. This effect is independent of the
      microdialysis flow rate and does not result from tissue injury following probe
      implantation. This finding clearly illustrates that microdialysis can influence
      the pathological conditions under investigation.

PMID- 8870796
TI  - Delayed neuronal damage following focal ischemic injury in stroke-prone
      spontaneously hypertensive rats.
AB  - We detected the delayed accumulation of 45Ca in the lateral part of the striatum
      3 days after distal middle cerebral artery (MCA) occlusion in stroke-prone
      spontaneously hypertensive rats (SHRSP). However, the mechanism of delayed
      neuronal damage in the striatum, which is not supplied by the occluded MCA,
      remains unknown. The aim of this study was to evaluate whether the delayed damage
      involves alterations in the extracellular release of neurotransmitter monoamines
      and amino acids. Chronological changes in the distribution of neuronal damage
      were determined by 45Ca autoradiography. The microdialysis probes were inserted
      into either the medial or lateral part of the striatum. The dialysate content of
      monoamines, their metabolites and amino acids was determined by analytical
      techniques. 45Ca accumulation was detected only in the cortex and corpus callosum
      by 24 hours postischemia and extended to the pyramidal tract, thalamus and
      lateral portion of the striatum by 3 days. A 3-fold increase in glutamate
      content, and a 2-fold increase in dopamine content were observed only in the
      lateral part of the striatum following ischemia. The results suggest that
      excessive release of glutamate and dopamine is related to delayed neuronal damage
      that occurs in the lateral part of the striatum in this ischemic model.

PMID- 8870797
TI  - The measurement of extracellular inorganic phosphate gives a more reliable
      indication for severe impairment of cerebral cell function and cell death than
      the measurement of extracellular lactate.
AB  - The measurement of cerebral extracellular lactate levels has been suggested to be
      used to monitor cerebral function in intensive care However, although an increase
      of extracellular lactate levels is a sensitive parameter for increased cellular
      activity in general, it will be shown that its prognostic value is limited in
      regard to the severity of the impairment of cellular function. As an alternative
      the measurement of the extracellular levels of inorganic phosphate (IP) or
      adenosine is proposed here: Whereas extracellular lactate levels increased
      rapidly to about the same extents during ischemia (IS) and spreading depression
      (SD), IP rose during IS only. Adenosine, on the other hand, increased during both
      events to a different degree. If, therefore, lactate was the only parameter to be
      monitored after a cerebral insult, the results would not allow to discriminate
      between a transient, spontaneously recovering event as a SD and a long lasting or
      an irreversible loss of cell function as in persisting ischemia/hypoxia. The
      measurement of IP, therefore, seems to be more suitable than that of lactate or
      adenosine since IP will appear within the extracellular space only after a
      sustained failure of membrane function. Thus, the measurement of IP changes
      turned out to be the more useful parameter for intensive care supervision.

PMID- 8870798
TI  - A concept for the introduction of cerebral microdialysis in neurointensive care.
AB  - Before microdialysis (MD) can be introduced into the clinic as an improved method
      of cerebral monitoring, certain ethical, methodological and clinical factors must
      be considered. Access to the brain for probe insertion is offered by craniotomy
      or by routine intracranial pressure (ICP) monitoring and the additional lesion is
      minimal. Care must be taken that the two devices do not interfere with each
      other. In contrast to ICP monitoring, MD provides information about multiple
      aspects of brain metabolism. We can monitor either still intact tissue to prevent
      additional damage, or injured brain to decide on and control therapies. The
      parameters used must reflect pathological changes an early stage, and the
      analysis should be available on-line or immediately after sample collection. The
      effects off factors such as tube length and flow rate on the behaviour of the
      chosen parameters (in our case on-line pH, radical scavengers and uric acid) in
      the MD set-up must be investigated in vitro and in animal models before use in
      the clinic. The range of non-pathological values of parameters of interest in
      human brain should be known For this purpose we took measurements during an
      extracranial-intracranial bypass operation, and were able to compare values with
      those in a severely damaged brain. The mutual chronology of parameter changes and
      clinical events must be clear. Future aspects include the use of low-flow methods
      offering nearly 100% recovery, improved analytical methods, and combination of MD
      with other monitoring methods to obtain more exact information.

PMID- 8870799
TI  - Lactic acid and amino acid fluctuations measured using microdialysis reflect
      physiological derangements in head injury.
AB  - We examined the extracellular neurochemical milieu in 34 head injured patients
      using microdialysis while simultaneously monitoring intracranial pressure,
      cerebral perfusion pressure, and jugular venous oxygen saturation. Derangements
      of anaerobic metabolism reflected by increased lactate and lactate/pyruvate
      ratios, and release of amino acids were seen at the same time as physiological
      deterioration in the majority of instances. Clinical microdialysis may provide
      insights into the neurochemistry of head injury, and such information may lead to
      new methods of monitoring and treating head injured patients.

PMID- 8870800
TI  - Glutamate release and cerebral blood flow after severe human head injury.
AB  - Elevations of extracellular glutamate have been found in patients with prolonged
      brain ischemia and focal cerebral contusions, following severe head injury. About
      30% of severely head injured patients develop cerebral ischemia, defined as CBF <
      18 ml/100g/min. Patients with both global and regional cerebral ischemia have the
      worst outcome. However, the relationship between CBF and EAA release is not well
      understood in head injured humans, and may differ from the findings in normal
      animals. To study the relationship between EAA release and CBF after severe head
      injury, we performed cerebral blood flow measurements using stable xenon enhanced
      computed tomography and correlated these with glutamate release in the
      extracellular fluid, measured by continuous microdialysis, in 25 severely head
      injured patients. Sustained cerebral blood flow reductions below the threshold
      for ischemic neuronal damage was closely related to massive excitatory amino acid
      release, as in previous animal studies. In patients without secondary ischemia,
      or focal contusions, delayed post-traumatic glutamate release appeared to be only
      transient or did not occur at all.

PMID- 8870801
TI  - Increased levels of glutamate in patients with subarachnoid haemorrhage as
      measured by intracerebral microdialysis.
AB  - Cerebral ischemia associated with subarachnoid haemorrhage (SAH) may have severe
      consequences for neuronal function leading to reversible or permanent
      neurological deficits. The excitatory amino acid neurotransmitters, such as
      glutamate, have been shown to be of particular importance for ischemic neuronal
      damage. In seven patients who underwent early surgery for a ruptured intracranial
      aneurysm, microdialysis of glutamate was performed in order to monitor local
      metabolic changes in the medial temporal tall patients) and subfrontal cortex
      (four patients). The preliminary results indicate that: (i) extracellular
      glutamate concentrations may rise to very high levels after SAH and aneurysm
      surgery, (ii) the increased levels of excitatory amino acids correlate with the
      clinical course, and (iii) a rise in extracellular glutamate in one region is not
      necessarily paralleled with a rise in the other, as seen by the simultaneous
      sampling from two different vascular territories.

PMID- 8870802
TI  - Microdialytic monitoring of the cortex during neurovascular surgery.
AB  - Using microdialysis combined with suitable analytical methods, levels of
      metabolites in the extracellular fluid of the cerebral cortex were monitored
      during neurovascular surgery (9 aneurysm and 5 bypass operations). Our aim was to
      use microdialysis to detect any local ischaemia which could be caused by brain
      retraction, temporary clipping and dissecting manoevres. For this purpose,
      parameters were quantified whose levels in the dialysate are known to be
      influenced by ischaemia (on-line pH, ascorbic acid, uric acid, glutathione,
      cysteine, glucose, lactate). In the aneurysm series, the on-line pH fell after
      introduction of the retractor, and rose after removal: also, in many cases,
      levels of ascorbic acid, glutathione and lactate increased and glucose decreased.
      These changes are all in accordance with ischaemic conditions in the region of
      the probe; they disappeared at the end of retraction, or sometimes even before.
      During the bypass operations, there were no marked changes in on-line pH or in
      any of the measured parameters. However, in 2 of these patients ascorbic acid,
      uric acid and glucose levels were very high during the whole measurement,
      indicating possible changes in metabolism caused by inadequate perfusion (carotid
      artery stenosis). We conclude that microdialysis is a sensitive method of
      detecting intraoperative changes in cerebral metabolism.

PMID- 8870803
TI  - In-vivo microdialysis study of extracellular glutamate response to temperature
      variance in subarachnoid hemorrhage.
AB  - Neurochemical changes may precede the development of clinical signs in
      neurological disease. Early identification of such changes may offer an
      opportunity to avoid or treat complications. Under experimental conditions,
      extracellular levels of glutamate and other amino acids can be monitored by in
      vivo microdialysis in cerebral ischemia, head trauma and epilepsy. Data on the
      release of glutamate under ischemic conditions in humans are limited. There is no
      published data on the effects of temperature variation or other manipulations on
      the extracellular glutamate levels in humans. We report for the first time, the
      effects of changes in temperature on the extracellular cerebral glutamate levels
      as measured by in-vivo microdialysis, the dialysate being collected before,
      during and after cooling in four patients with subarachnoid hemorrhage. Three of
      the patients had in-vivo microdialysis carried out postoperatively. One patient
      underwent microdialysis three days prior to the surgical clipping of the
      aneurysm. In all patients, mild head cooling resulted in a significant decrease
      in extracellular glutamate levels. The effect of cooling was most apparent when
      the extracellular glutamate concentrations were high. In two patients, the
      extracellular glutamate levels increased sharply with fever but returned to
      normal once the temperature normalized. In vivo microdialysis can be used to
      measure extracellular glutamate and other neurotransmitters with minimal
      discomfort in awake humans. This technique offers a unique opportunity to monitor
      the neurochemistry in critically ill patients and it may aid in developing
      therapeutic intervention strategies to minimize undesired chemical responses.

PMID- 8870804
TI  - Antiepileptic drug pharmacokinetics in patients with epilepsy using a new
      microdialysis probe: preliminary observations.
AB  - Using a newly developed microdialysis probe which allows continuous monitoring of
      drugs in blood, we have studied the pharmacokinetics of various antiepileptic
      drugs (carbamazepine, and its primary metabolite carbamazepine-epoxide, phenytoin
      primidone and phenobarbitone) in 5 patients (2 male, 3 female, aged 40-50 years)
      with intractable epilepsy. It was observed that microdialysate pharmacokinetic
      profiles were comparable to those obtained by direct blood sampling. Furthermore,
      patients found the microdialysis probe highly acceptable and desirable and indeed
      preferable to that of blood sampling.

PMID- 8870805
TI  - A new screwing device for fixing a microdialysis probe in critical care patients.
AB  - We describe a new, easy method which extends the use of clinical microdialysis to
      neurotrauma patients who primarily do not need a decompressing surgical
      intervention. In all head trauma patients in whom a Camino ICP-monitor is
      indicated a second hole (2 mm in diameter) is made, and the MD probe is fixed
      using the new screwing device. Before clinical use the system was tested during
      postmortem, confirming correct cortical placement of the probe in almost all
      cases. Two case reports are presented including their metabolic values. An
      extension to patients with non-traumatic brain disorders might be a future
      aspect.

PMID- 8870806
TI  - A novel microdialysis probe designed for clinical use: potential analytical and
      therapeutic applications.
AB  - Significant obstacles to the use of microdialysis in the clinic for diagnostic or
      therapeutic purposes include the production of dedicated entry port through the
      skull and the formation of a tract by the insertion of a probe into the
      parenchyma. We have developed a microdialysis probe that is minimally invasive
      and can be combined with an intracranial pressure probe, recording electrode, or
      other intracranial probe, that is minimally invasive. Yet the surface area of
      this probe is very high, permitting high recovery efficiencies even at relatively
      high flow rates. This probe design makes possible minimally invasive measurement
      of the peroxidation product, uric acid, and excitatory amino acids, two analytes
      that increase in experimental traumatic brain injury in animals. Moreover, its
      large surface area makes therapeutic applications of microdialysis probes in the
      brain potentially feasible. A pilot evaluation of the ability of microdialysis to
      have therapeutic benefit in limiting experimental excitotoxin lesions induced in
      rat striatum by N-methyl-D-aspartate (NMDA) is reported.

PMID- 8870807
TI  - Microdialytic monitoring during a cardiovascular operation.
AB  - In an aorta-coronary bypass operation, the heart is excluded from the circulation
      for many minutes, leading to ischemia. During this time the heart is cooled in
      order to mitigate damage. Microdialysis has been shown to be very suitable for
      detecting ischaemic changes e.g. in brain. We therefore used this method to study
      the time courses of several neurochemical parameters which have been shown to
      indicate ischaemia in animal models (ascorbic acid, glutathione, cysteine, uric
      acid, glucose, lactate and pH), during such a bypass operation. Three patients
      were investigated, the microdialysis probe being inserted into the
      interventricular septum of the heart. Our results show that microdialysis is
      technically feasible in the human heart in a clinical setting, although the
      operation becomes more demanding for the surgeon. All the above-mentioned
      parameters could be detected in the heart muscle. Some of them showed changes
      characteristic of ischaemia, and the effects of cooling on the metabolism could
      also be noted. Long term measurements are planned to enable delayed damage to be
      disclosed.

PMID- 8870809
TI  - Effects of fructose ingestion on sorbitol and fructose 3-phosphate contents of
      erythrocytes from healthy men.
AB  - To investigate the effect of fructose ingestion on sorbitol and fructose 3
      phosphate (F3P) in erythrocytes, we administered 50 g fructose with and without
      treatment with an aldose reductase inhibitor, epalrestat, to seven healthy,
      normal-glucose-tolerant, male volunteers aged 20-43 years. The same subjects were
      given 50 g glucose on another day. The sorbitol and F3P contents in their
      erythrocytes increased significantly, reaching peak levels at 60 min and 180 min,
      respectively, following fructose in gestion. On the other hand, glucose ingestion
      did not cause any statistically significant change in sorbitol content in their
      erythrocytes, although it significantly elevated their F3P content. Treatment
      with epalrestat had no significant effect on incremental changes in erythrocyte
      sorbitol and F3P content following fructose ingestion. This suggests that oral
      fructose may be converted directly to sorbitol and F3P in erythrocytes instead of
      being converted via glucose. Thus, the dietary intake of fructose may affect the
      concentrations of sorbitol and F3P in erythrocytes in normal men.

PMID- 8870810
TI  - Detection of anti-myeloperoxidase antibodies in the serum of patients with type 1
      diabetes mellitus.
AB  - Anti-myeloperoxidase (anti-MPO) antibodies were detected in 34 of 88 (38%)
      patients with type 1 diabetes mellitus but in only 3 of 55 (5.7%) healthy
      subjects and in 4 of 20 patients with autoimmune disease. Specificity of anti-MPO
      antibodies was assessed by MPO inhibition studies. No relationship was found
      between the occurrence of anti-MPO and anti-thyroperoxidase antibodies. Levels of
      soluble intercellular adhesion molecule 1 (ICAM-1) were found to be higher in
      anti-MPO antibody-positive (n = 28, 508 +/- 126 ng/ml) than in anti-MPO antibody
      negative (n = 58, 438 +/- 140 ng/ml: P < 0.05) patients. A state of chronic
      neutrophil activation has been described in diabetes mellitus. As anti-MPO
      antibodies can stimulate neutrophils to damage endothelial cells in systemic
      vasculitis, this suggests that a similar mechanism may be operative in the
      development of diabetic angiopathy.

PMID- 8870812
TI  - Diabetes-induced changes in the contractility of the aorta and pA2 of nifedipine
      in the rat.
AB  - Diabetes-induced changes in the calcium influx and contractile responses of
      aortic rings to various drugs were investigated in streptozotocin-treated rats.
      Diabetes is associated with calcium influx into the aortic rings (1.5-and 2.5
      fold, respectively, after either KCl or noradrenaline stimulation compared with
      normal). The maximum KCl-induced contraction of the arorta in diabetic rats was
      reduced by 38%, but the EC50 of KCl remained unchanged. The pA2 of nifedipine for
      inhibiting the contractile response of aorta to KCl decreased one order of
      magnitude in the diabetic rats (8.26 vs 9.03 for non-diabetic rats). It is
      concluded that diabetes reduces the sensitivity of aortic tissue to nifedipine
      and may affect the stimulation-contraction coupling of vascular smooth muscle in
      such a way that a higher influx of calcium results after stimulation and that
      this may be responsible for diabetes-induced vascular complications.

PMID- 8870808
TI  - Insulin resistance in non-insulin-dependent diabetes mellitus. A review.

PMID- 8870811
TI  - HLA class II is associated with the frequency of glutamic acid decarboxylase M(r)
      65,000 autoantibodies in Japanese patients with insulin-dependent diabetes
      mellitus.
AB  - Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both
      caucasian and Japanese patients with insulin-dependent diabetes mellitus (type
      1), while the type 1-associated HLA haplotypes differ. In the present study, we
      analyzed GAD65Ab in relation to HLA-DQ and -DR alleles in Japanese type 1
      patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1,
      23% long-duration type 1, 56% slowly progressive type 1, 3% type 2 patients, and
      1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency
      was higher in short-duration patients with DRB1*08 allele (100%, Pc < 0.05).
      GAD65Ab frequencies in DQB1*0302, DQB1*0303, and DRB1*09-positive, long-duration
      type 1 patients were lower than those in short-duration type 1 patients (14%,
      19%, and 20%, Pc < 0.02 compared with short-duration type 1, 90%, 75%, and 71%,
      respectively), while the frequency varied less in DQB1*04 individuals (44% and
      30% in short- and long-duration type 1 patients, respectively). These findings
      were also observed among patients with DRB1*04, i.e., the haplotype DRB1*0405
      DQB1*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short-
      and long-duration type 1 patients, respectively), while DRB1*04xx-DQB1*0302
      showed lower frequency in long-duration type 1 than short-duration (13% and 100%,
      respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this
      association might be affected by disease duration in Japanese type 1 patients.

PMID- 8870813
TI  - Increased prothrombin fragment 1 + 2 and D-dimer in first-degree relatives of
      type 2 diabetic patients. Prethrombotic state in relatives of type 2 diabetic
      patients.
AB  - To evaluate whether or not activated coagulation is present in the preclinical
      phases of type 2 diabetes mellitus, we studied 46 non-diabetic first-degree
      relatives of type 2 diabetic patients and 21 matched controls with no family
      history of diabetes. We determined the plasma levels of prothrombin fragment 1 +
      2, D-dimer, fibrinogen, plasminogen activator inhibitor type 1, tissue
      plasminogen activator, von Willebrand factor and coagulation factors VII and
      VIII. Glucose tolerance, beta-cell function and insulin sensitivity were assessed
      in all subjects by a continuous glucose infusion of 5 mg.kg ideal body weight
      1.min-1 for 60 min with model assessment of glucose, insulin and C-peptide
      values. Plasma levels of prothrombin fragment 1 + 2 (median 1.24 vs 0.68 nmol.l
      1; P = 0.0001) and D-dimer (331 vs 254 micrograms.l-1 UEF; P = 0.018) were higher
      in relatives, without significant differences in the other haemostatic variables.
      Relatives showed higher fasting (5.5 vs 4.9 mmol.l-1, P = 0.004) and post
      infusion (9.3 vs 8.3 mmol.l-1, P = 0.02) serum glucose, no differences in insulin
      or C-peptide levels, lower beta-cell function (122% vs 147%; P = 0.02) and no
      significant differences in insulin sensitivity. Fifteen relatives were glucose
      intolerant and had lower beta-cell function and insulin sensitivity than glucose
      tolerant relatives. Both subsets of relatives exhibited higher levels of
      prothrombin fragment 1 + 2 and D-dimer than control subjects. Thus, first-degree
      relatives of type 2 diabetic patients present an activated coagulation, even in
      the absence of minor degrees of glucose intolerance. These abnormalities can play
      a role in the pathogenesis of cardiovascular diseases frequently seen at
      diagnosis of type 2 diabetes.

PMID- 8870814
TI  - Lymphokine release during co-culture of human lympho-mononuclear cells and fresh
      or cultured human, porcine and bovine pancreatic islets.
AB  - In this study we evaluated whether isolated human (HI), porcine (PI) and bovine
      (BI) islets, either fresh (Fr) or cultured for 4 weeks (4 w) affect cytokine
      release from human lymphomononuclear cells (LMC) differently. We prepared LMC
      from peripheral blood by density gradient purification and co-cultured 1 x 10(6)
      LMC for 24 h with 100 hand-picked islets, either within 48 h of isolation or
      after culture for 4 weeks. Soluble interleukin-2 receptor (IL-2R), interferon
      gamma (IFN), interleukin-4 (IL-4) and interleukin-10 (IL-10) were measured by
      sandwich enzyme-linked immunoadsorbent assay. Compared with controls (Ctrl, LMC
      without islets), Fr-HI, Fr-PI and Fr-BI caused a similar increase of IL-2R and
      IFN release, whereas 4 w-HI and 4 w-BI did not lead to any significant production
      of these two cytokines. IL-10 concentrations increased with Fr-PI and Fr-BI, but
      not with Fr-HI, and no major effect of the 4-week culture was seen. IL-4 levels
      were below the detection limit of the method used in these experiments. Thus,
      fresh allo- and xeno-islets caused a similar increase of the release of cytokines
      known to be markers of Th1 activation, whereas the release of IL-10, a marker of
      Th2 activation, increased with xeno-, but not with allo-islets; culturing the
      islets for 4 weeks decreased Th1, but not Th2 activation.

PMID- 8870815
TI  - Biosynthesis of the endogenous cyclic adenosine monophosphate (AMP) antagonist,
      prostaglandylinositol cyclic phosphate (cyclic PIP), from prostaglandin E and
      activated inositol polyphosphate in rat liver plasma membranes.
AB  - The endogenous cyclic adenosine monophosphate (AMP) antagonist, cyclic PIP, has
      been identified as a prostaglandylinositol cyclic phosphate. It inhibits protein
      kinase A 100% and activates protein serine phosphatase about sevenfold. It is
      biosynthesized by an enzyme of the plasma membrane when the assay mixture
      contains adenosine triphosphate (ATP), Mg2+, prostaglandin E and a novel inositol
      polyphosphate, which cannot be substituted by commercially available inositol
      phosphates. This novel inositol polyphosphate is a very labile compound. On anion
      exchange chromatography it elutes in the range of ATP, which may indicate the
      presence of three phosphate groups. It adsorbs on charcoal, which suggests the
      presence of a hydrophobic component, possibly a guanosine. Pyrophosphates
      obtained from inositol 1,4- and inositol 2,4-bisphosphate are accepted by cyclic
      PIP synthetase for the synthesis of cyclic PIP. The biosynthesis is characterized
      by enzyme kinetic parameters like dependence on time, enzyme and substrate
      concentration. The pH optimum of the enzyme is in the range 7.5-8. The enzyme
      functions optimally with prostaglandin E and poorly with prostaglandin A as the
      substrate. The presence of fluoride in the assay causes a three- to fourfold
      increase in cyclic PIP synthesis, which may be correlated with activation via G
      proteins. These data support previous reports on the chemical structure and
      action of cyclic PIP. With respect to the possible isomers of cyclic PIP, these
      indicate that it is most likely the C4-hydroxyl group of the inositol which binds
      the C15-hydroxyl group of prostaglandin E. A model of hormone-stimulated
      synthesis of cyclic PIP is proposed: phospholipase A2 and phospholipase C,
      activated by G proteins upon alpha-adrenergic stimulation, liberate either
      unsaturated fatty acids or inositol phosphates, which are transformed to
      prostaglandins and to novel inositol polyphosphate with an energy-rich bond. The
      cyclic PIP synthetase combines these two substrates to cyclic PIP.

PMID- 8870817
TI  - Known type 2 diabetes mellitus among the Kuwaiti population. A prevalence study.
AB  - The reported prevalence of type 2 diabetes among the Kuwaiti population varied
      from one source to another. This study was undertaken to define the magnitude of
      the problem and to suggest plans for future diabetic care. All type 2 Kuwaiti
      diabetic subjects registered and continuing to attend regularly in two health
      areas Mubarak Health Area (MHA) and Farwania Health Area (FHA)] were selected for
      the study. There were 3222 in MHA and 5114 in FHA among the Kuwaiti population
      aged 20 years and above, accounting for a total crude prevalence of 7.6% in both
      health areas and for a prevalence rate of 5.6% in MHA and 10.0% in FHA. The age
      specific prevalence of type 2 diabetes in both areas combined rose from 2.639 per
      100 population in the age group 20-39 years to 15.350% and 26.252% in the age
      groups 40-59 and 60 and above, respectively. The female to male ratio was 1.7,
      1.6, 1.1, respectively, in MHA and 1.7, 2.0, 0.9 in FHA for the age groups 20-39,
      40-59, and 60 and above. This study shows that type 2 diabetes is a major public
      health problem in Kuwait, with a female preponderance. Obesity is a
      characteristic feature of the population studied, with a mean body mass index of
      31.8 +/- 6.3 and 28.5 +/- 5.1 in women and men, respectively. A positive family
      history of diabetes mellitus was reported in 63% of the diabetic subjects. There
      is a need to standardize methods of reporting and to plan a national screening
      survey.

PMID- 8870816
TI  - An immunological and genetic study of patients with gestational diabetes
      mellitus.
AB  - The aim of the study was to evaluate the frequency of islet cell (ICA) and
      insulin (IAA) antibodies and of HLA antigen typing in a group of subjects
      diagnosed with gestational diabetes mellitus (GDM) in a screening-diagnostic
      program during pregnancy. ICA, complement-fixing (CF) ICA and other
      autoantibodies, absolute number and percentage of lymphocyte subpopulations, and
      HLA antigens were evaluated in 68 women with GDM and compared with those of
      matched controls. ICA were found in 2 (2.9%) and IAA in 1 (1.5%). Both ICA
      positive women had CF-ICA; one of them was receiving insulin therapy. while the
      other was on a special diet. No correlations were found between ICA and IAA, nor
      between IAA and insulin treatment. As far as lymphocyte subsets were concerned,
      we found a significant increase in the absolute number of total and activated
      (CD3+HLA-DR+) T lymphocytes and a significant increase in the absolute number and
      percentage of suppressor/cytotoxic T lymphocytes (CD8) and NK lymphocytes (CD57)
      in GDM patients compared with normal pregnant controls. Concerning frequency for
      HLA A, B, C, DR antigens in the GDM population, only Cw7 was found to be
      significantly increased and A10 significantly decreased in comparison with
      controls. Our study suggests that GDM is a heterogeneous disorder in which few
      patients present with the immunologic and genetic markers of type 1 diabetes.

PMID- 8870818
TI  - A rapid qualitative method to assess in vitro immunobarrier competence of
      pancreatic islets containing alginate/polyaminoacidic microcapsules.
AB  - A quick method for the qualitative evaluation of immunoisolatory properties
      associated with islet-containing alginate/poly-L-ornithine (AG/PLO) microcapsules
      is described. In particular, we examined a new AG/PLO coherent microcapsule (CM)
      prototype that was recently developed in our laboratory, although the procedure
      could be applicable to other capsule types as well. We observed no binding of
      immunoglobulins (Ig) contained in islet cell antibody (ICA)-positive human sera
      (> 60 Juvenile Diabetes Foundation units, JDT U) to pig islets, enveloped within
      AG/PLO CM, under indirect immunofluorescence examination. Also, CM were shown to
      inhibit human lymphocyte proliferative capacity fully, as assessed by the 3H
      thymidine incorporation rate, in in vitro mixed xenogeneic pig islet/human
      lymphocyte co-cultures. These results provided us with a preliminary method to
      attempt standardization of basic physical/chemical properties which should be
      associated with an immunoisolatory membrane for islet allo/xenograft
      immunoprotection.

PMID- 8870819
TI  - Effect of biotin on glucokinase activity, mRNA expression and insulin release in
      cultured beta-cells.
AB  - Biotin is known to influence hepatic glucokinase (GK) expression both at a
      transcriptional and at a translational level. The aim of the present paper was to
      investigate the effect of biotin on pancreatic GK. For this purpose, RIN1046-38
      cells were cultured in the presence of different biotin concentrations for
      different times; there-after, GK mRNA expression, GK activity and insulin release
      were studied. Results demonstrated that biotin has a biphasic effect on GK mRNA
      expression, being stimulatory after short-term treatment and inhibitory after
      longterm treatment. GK activity was increased after long-term treatment. Insulin
      release was not affected by biotin treatment. These data suggest that biotin may
      influence glucose metabolism also by acting directly at the level of beta-cells.

PMID- 8870820
TI  - Different binding and degradation of proinsulin, insulin and insulin-like growth
      factor-1 (IGF-1) in cultured renal proximal tubular cells. Implications for the
      prolonged serum half-life of proinsulin.
AB  - Recent studies have reported that elevated proinsulin levels are indicative of an
      increased cardiovascular risk. Renal proximal tubular cells represent a major
      site for the metabolism of insulin-like hormones after glomerular filtration into
      the tubular lumen. To determine the binding and degradation of proinsulin in
      comparison with insulin and insulin-like growth factor-1 (IGF-1), we have used a
      rabbit proximal tubular cell line (PT-1). As confirmed by electron microscopy. PT
      1 cells exhibit bipolar differentiation, demonstrating apical microvilli and
      invaginations of the basolateral membrane. To allow selective incubation of both
      compartments, cells were grown on filter membranes. Performing equilibrium
      binding assays with 125I-labelled hormones, severalfold higher binding was found
      at the apical than at the basolateral cell membrane, with the capacity range IGF
      1 > insulin > proinsulin. Half-maximal displacement of 125I-labelled insulin and
      IGF-1 was observed at 0.6 and 2 nM, respectively, while crossover binding to the
      alternate receptor occurred with a 10- to 100-fold lower affinity. Half-maximal
      displacement of 125I-proinsulin binding was obtained at approx. 8 nM proinsulin
      and insulin, whereas IGF-1 was 10-fold less potent. The relative degradation of
      specifically bound tracer was lowest for proinsulin (apical 10%, basolateral:
      13%). IGF-1 was degraded by 20% at the apical cell membrane, and up to 78% at the
      basolateral membrane. In contrast, almost the total amount of insulin bound was
      degraded at both membrane sites (apical 99%, basolateral: 83%). These results
      suggest separate insulin and IGF-1 receptors while proinsulin binds with high
      affinity to a third insulin-like receptor on the apical membrane of PT-1 cells.

PMID- 8870821
TI  - Long-term survival and function of isolated bovine pancreatic islets maintained
      in different culture media.
AB  - Bovine islets are being evaluated for their potential in transplantation studies.
      We studied the recovery, morphology, and function of purified bovine islets
      cultured up to 4 weeks under varying conditions. Approximately 60% of the initial
      islet mass could be recovered after 4 weeks at 37 degrees C in CMRL 1066 or M 199
      culture medium, and the cultured islets were well preserved histologically and
      viable both in vitro and in vivo. On the other hand, culture with RPMI 1640
      caused disaggregation of the islets within a few days, with altered in vitro
      viability. Thus, culturing purified bovine islets with appropriate media is a
      suitable procedure to maintain islet mass, morphology, and function in the long
      term.

PMID- 8870822
TI  - Prevalence of diabetes in elderly patients requiring permanent cardiac pacemaker
      insertion.
AB  - Diabetes mellitus increases the rate of atrioventricular block after a myocardial
      infarction; right bundle branch block is more common than expected in the
      diabetic outpatient population. We decided to assess whether diabetic subjects
      were more likely to need permanent cardiac pacemaker insertion. Data from
      patients in Leicestershire who had undergone permanent cardiac pacemaker
      insertion during a 4-year period were analysed. The capture recapture technique
      was used: Hospital Activity Analysis data as capture, ward admission book and
      case note confirmation as recapture. Diabetes coding accuracy was confirmed from
      the central register and from an analysis of 100 sets of case notes. The number
      of these patients with diabetes was then recorded. Data for the reference
      population was obtained using a survey of a market town in Leicestershire. There
      were 688 patients, most (79%) aged over 65 years. Our analysis was performed on
      this group. Of this age group undergoing pacemaker insertion. 11.1% was diabetic.
      In the same age group, 8.3% of the controls were diabetic: a relative risk of
      1.34 (P < 0.01, 95% confidence interval 1.25-1.44). This relative risk is likely
      to be an underestimate. The aetiology of this excess risk is uncertain: it is
      most likely due to ischaemic heart disease, but microangiopathy or increased
      cholinergic sensitivity may play a role.

PMID- 8870823
TI  - Recent advances in defining the neuropathology of schizophrenia.
AB  - The search for the defining neuropathology of schizophrenia continues to be one
      of the highest priority areas of research into this severely debilitating and
      common neuropsychiatric disorder. While lesions that are diagnostic of the
      disorder have not yet been identified, recent efforts employing molecule-specific
      probes and quantitative methods of analysis have enumerated many potentially
      important findings in the brains of patients with schizophrenia that warrant
      confirmation and elucidation. In this review, the major findings of six broad
      areas of neuropathological investigation are summarized and discussed. While
      substantial controversy exists in all areas, in sum: (1) diagnostic
      neuropathological investigations find only assorted and nonspecific abnormalities
      in the brains of schizophrenics that are likely to be representative of lesions
      found in age-compatible control groups; (2) morphometric studies of gross
      structures generally confirm the clinical in vivo neuroimaging findings of
      enlarged ventricles, decreased size of ventromedial temporal lobe structures, and
      decreased parahippocampal cortical thickness; (3) morphometric microscopy studies
      find frequent alterations in neuron density and decreased neuron size in limbic,
      temporal, and frontal regions; (4) investigations of connectivity are at an early
      stage but describe abnormal dendritic spine densities in the cortex, various
      changes in synaptic vesicle protein expression in limbic, temporal, and frontal
      cortices, and alterations in glutamatergic, catecholaminergic, and intrinsic
      innervation in anterior cingulate cortex- together, these findings suggest a
      "miswiring" in the schizophrenic brain; (5) investigations of aberrant
      neurodevelopment in schizophrenia describe abnormalities in cortical
      cytoarchitecture and several developmentally regulated proteins in the
      hippocampal region suggesting abnormal neuronal migration, differentiation,
      and/or cell pruning; and (6) studies of neurodegeneration and neural injury find
      a general lack of neurodegenerative disease lesions or ongoing astrocytosis that
      would indicate post-maturational neural injury.

PMID- 8870824
TI  - Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau
      protein kinase (TPK) I/glycogen synthase kinase-3 beta and cyclin-dependent
      kinase 5, a component of TPK II.
AB  - Using immunohistochemistry, we examined the localization of four types of proline
      directed kinases in the brains of control rats and in the brains of non-demented
      aged human subjects, subjects with Alzheimer's disease and those with Down's
      syndrome. The four kinases were: cyclin-dependent kinase (cdk) 5, a component of
      tau protein kinase (TPK) II; TPK I/glycogen synthase kinase (GSK)-3 beta; GSK-3
      alpha; and mitogen-activated protein kinase (MAPK/ERK2). Each of these kinases
      has been reported to promote the hyperphosphorylation of tau protein in vitro.
      The kinases were located essentially in neurons, although the intensity and
      distribution of labeling varied. Antiserum for cdk5 showed the most preferential
      and consistent labeling of intraneuronal neurofibrillary tangles (NFT). Antiserum
      for TPK I/GSK-3 beta also labeled intraneuronal NFT. Double immunolabeling for
      TPK I/GSK-3 beta and tau 1 showed that TPK I/GSK-3 beta was closely associated
      with NFT. Antiserum for GSK-3 alpha labeled neurons weakly, and the intensity of
      labeling did not differ between neurons with and without NFT. Antiserum for MAPK
      labeled neurons in superficial cortical layers, but NFT appeared in both
      superficial and deep cortical layers. These findings suggest that cdk5 and TPK
      I/GSK-3 beta are the critically important kinases for the generation in vivo of
      hyperphosphorylated tau, the main component of the paired helical filaments in
      NFT.

PMID- 8870825
TI  - Apoptosis in the aged dog brain.
AB  - Apoptosis similar to that seen in Alzheimer's disease patients was found in the
      brain of aged dogs by the TUNEL method of detecting in situ DNA fragmentation.
      Apoptosis was observed in both neurons and glial cells, and was morphologically
      characterized by round and swollen cytoplasm and aggregated nuclear chromatin,
      although these changes were slight. Neurons and astrocytes in the gray matter and
      oligodendrocytes in the white matter were affected. The number of ApopTag
      positive brain cells increased slightly with age, but was not correlated to the
      number of senile plaques. A good correlation between the number of ApopTag
      positive cells and the dementia index was clearly found. The present study
      indicates that brain cell apoptosis could account for dementia in aged dogs and
      suggested that aged dogs may be useful as a simplified animal model for
      Alzheimer's disease in man.

PMID- 8870826
TI  - Pathological study of Japanese quail embryo with acid alpha-glucosidase
      deficiency during early development.
AB  - A pathological study was performed on the tissues of 11 Japanese quail embryos
      with type II glycogen storage disease (GSD II) between incubation day (ID) 3 and
      ID 15. Accumulation of glycogen in vacuoles derived from lysosomes was first seen
      in cardiac muscle at ID 3, in liver at ID 5, in wing muscle at ID 7, and in
      pectoral muscle at ID 10. The number and size of the glycogen vacuoles gradually
      increased during development, especially in cardiac muscle. Cytoplasmic glycogen
      particles, showing the same density as membrane-enclosed glycogen particles, were
      first seen as masses in cardiac muscle at ID 3, in liver at ID 5, in pectoral
      muscle at ID 10, and in wing muscle at ID 15. The area of cytoplasm occupied by
      the glycogen particles increased during development. Myofibrillar degeneration
      was not seen, although myofibrils appeared in disarray in the early stages, as in
      normal embryos. This is the first study of the development of embryonic tissues
      of Japanese quails with GSD II. GSD II in the Japanese quail appears to be
      clinically analogous to the human late (juvenile)-onset disease, although the
      disorder starts at very early stages in quail embryos. Therefore, Japanese quails
      with GSD II can provide a model for elucidating the pathogenetic process of human
      GSD II.

PMID- 8870827
TI  - Spatiotemporal relationship of apoptotic cell death to lymphomonocytic
      infiltration in photochemically induced focal ischemia of the rat cerebral
      cortex.
AB  - In this study we examined the time course of apoptotic cell death after
      photochemically induced focal ischemia of the rat cerebral cortex. For
      unequivocal differentiation between apoptosis and necrosis two criteria of
      programmed cell death were used: terminal deoxyribonucleotidyl transferase
      mediated dUTP-digoxigenin nick end labeling (TUNEL) and morphological evidence of
      fragmentation and marginalization of nuclei. After photothrombosis, many TUNEL
      positive cells were found within the infarct region from 12 h to 3 days. By day 6
      they were preferentially located in the boundary zone of the infarct, and by day
      14 they had disappeared. A high proportion of TUNEL-positive cells displayed
      fragmentation or marginalization of their nuclei, indicating apoptosis. Neurons,
      but not T cells and macrophages, were apoptotic. Inflammatory infiltrates were in
      close contact to apoptotic neurons throughout the infarct areas at day 1 and in
      the boundary zone between days 2 and 6 after photothrombosis. In summary, our
      study shows that neuronal apoptosis after cerebral ischemia is a prolonged
      process to which leukocyte-derived cytokines may contribute. In contrast to
      autoimmune diseases of the nervous system, termination of the local inflammatory
      response after cerebral ischemia does not involve apoptosis.

PMID- 8870828
TI  - Serum prevents glutamate-induced mitochondrial calcium accumulation in primary
      neuronal cultures.
AB  - The effect of serum proteins on glutamate-induced mitochondrial calcium
      accumulation was studied in primary cortical and hippocampal cultures using
      oxalate-pyroantimonate staining with electron microscopy. Cultures were prepared
      from rat embryos on gestational day 17-19 and cultivated for 8 days in minimal
      essential medium (MEM) containing 5% native horse serum. At this time cultures
      were exposed for 5 min to 100 micro M or 1.0 mM glutamate, followed by recovery
      in either serum-free or serum-containing culture medium. Mitochondrial calcium
      accumulation was assessed before glutamate treatment, at the end of glutamate
      exposure, and after 5 min, 30 min, 6 h and 24 h of recovery. Under control
      conditions and at the end of glutamate exposure, mitochondria contained only a
      few calcium deposits. If cultures were placed in serum-free medium after
      glutamate treatment, mitochondria were progressively loaded with calcium. At 5
      min after glutamate exposure mitochondrial calcium deposits were prominent in
      both cortical and hippocampal cultures, followed by a further steady increase and
      neuronal death within 24 h. When cultures were allowed to recover after glutamate
      treatment in serum-containing MEM, calcium sequestration and ultrastructural
      changes of mitochondria were essentially absent, and neurons survived. No
      differences between cortical and hippocampal cultures were observed. The data
      demonstrate that prevention of glutamate neurotoxicity by serum proteins is
      associated with prevention of post-glutamate mitochondrial calcium accumulation.

PMID- 8870829
TI  - Up-regulation of major histocompatibility complex class II antigen expression in
      the central nervous system of dogs with spontaneous canine distemper virus
      encephalitis.
AB  - Major histocompatibility complex class II (MHC II) and canine distemper virus
      (CDV) antigen expression were compared by immunohistochemistry in the cerebellar
      white matter of ten dogs with naturally occurring canine distemper encephalitis.
      In addition, infiltrating mononuclear cells were characterized by employing poly-
      and monoclonal antibodies directed against human CD3, canine MHC II, CD5, B cell
      antigen and CDV-specific nucleoprotein. Positive antigen-antibody reaction was
      visualized by the avidin-biotin-peroxidase complex method on frozen sections.
      Histologically, neuropathological changes were categorized into acute, subacute,
      and chronic. In control brains, MHC II expression was weak and predominantly
      detected on resident microglia of the white matter and on endothelial,
      perivascular and intravascular cells. In CDV antigen-positive brains, MHC II was
      mainly found on microglia and to a lesser extent on endothelial, meningeal,
      choroid plexus epithelial, ependymal and intravascular cells. In addition,
      virtually all of the perivascular cells expressed MHC II antigen. CDV antigen was
      demonstrated most frequently in astrocytes. Of the perivascular lymphocytes, the
      majority were CD3-positive cells, followed by B cells. Only a small proportion of
      perivascular cells expressed the CD5 antigen. In addition, B cells and CD3 and
      CD5 antigen-positive cells were found occasionally in subacute and frequently in
      chronic demyelinating plaques. In acute encephalitis, CDV antigen exhibited a
      multifocal or diffuse distribution, and MHC II was moderately up-regulated
      throughout the white matter and accentuated in CDV antigen-positive plaques. In
      subacute encephalitis, moderate multifocal CDV antigen and moderate to strong
      diffuse MHC II-specific staining, especially prominent in CDV antigen-positive
      lesions, were observed. In chronic encephalitis, CDV antigen expression was
      restricted to single astrocytes at the edge of the lesions or was absent, while
      MHC II expression, especially prominent on microglia, was strongly up-regulated
      throughout the white matter, most pronounced in demyelinated plaques. In summary,
      in acute and subacute lesions without perivascular cuffs, MHC II expression
      correlated with the presence of CDV antigen. In contrast, in chronic lesions, MHC
      II expression on microglial cells was the most prominent despite a few CDV
      antigen-positive astrocytes, indicating that nonviral antigens may play an
      important role as triggering molecules for the process of demyelination.

PMID- 8870830
TI  - Glial expression of cytokines in the brains of cerebrovascular disease patients.
AB  - We examined the immunohistochemical localization of the proinflammatory cytokines
      tumor necrosis factor-alpha, lymphotoxin and interferon-gamma in 22 autopsy
      brains of patients with either cerebrovascular disease (CVD) or other
      neurological diseases as well as 2 non-neurological control brains. These
      cytokines were coexpressed mostly in the microglia/macrophages and in a few
      astroglia in the brains with acute cerebral infarction and cerebral hemorrhage.
      In cases with cerebral infarction, they were observed as early as 33 h after the
      onset of the illness and persisted for up to 40 days after the onset. In one
      patient with cerebral hemorrhage who survived for 4 h, the cytokine
      immunoreactive glial cells were confined to the margins of the hematoma. In
      contrast, the cytokine-immunoreactive glia were distributed diffusely in one
      patient with cerebral hemorrhage who died 12 days after the onset of the illness.
      Labeling for these cytokines was weak in the glial cells of control brains and
      those with neurodegenerative diseases, including Alzheimer's disease, Parkinson's
      disease and multiple system atrophy, in so far as there were no concomitant acute
      CVD foci. The present results indicate that proinflammatory cytokines are up
      regulated in the brains of patients with acute stroke, and suggest an early
      inflammatory response in human CVD.

PMID- 8870831
TI  - Distribution and characterization of microglia/macrophages in human brain tumors.
AB  - The role of inflammatory reactions in brain tumors is still unclear. In
      particular, there is little information about the participation of the
      microglia/macrophage cell system. We therefore investigated 72 surgical biopsy
      samples of brain tumors (astrocytoma, glioblastoma, oligodendroglioma,
      ependymoma, medulloblastoma, cerebral lymphoma, gangliocytoma, neurocytoma and
      germinoma) and the brains of eight cases with malignant gliomas that came to
      autopsy, using immunohistochemical markers for the monocyte/macrophage lineage
      (Ki-M1P, HLA-DR, KP1, My4, My7, Ki-M1, Ki-M6, EBM 11). These markers allowed us
      to characterize four subtypes of the microglia/macrophage cell system: ramified
      microglia, ameboid microglia, perivascular microglia and brain macrophages. Among
      the different tumors, glioblastomas and anaplastic gliomas showed the largest
      number of mixed cell populations, which consisted of macro-phages and ramified
      and ameboid microglia. In glial tumors of low malignancy fewer, predominantly
      ameboid, microglia were found. Neuronal tumors showed only a mild increase of
      microglia. Cerebral lymphomas contained macrophages diffusely distributed within
      the tumor center, while activated microglia were prominent at the border zone and
      in the adjacent brain tissue. The autopsy cases were used to study the
      morphometric distribution of microglia/macrophages. There was a significant
      increase of microglia/macrophages within the tumor, but no differences were seen
      between central and peripheral tumor areas. The non-neoplastic gray and white
      matter contained more microglial cells than controls. We conclude that the
      distribution pattern of ameboid and ramified microglial cells and macrophages is
      distinct in most of the investigated tumor types, underlining the complex
      immunological function of the microglia/macrophage cell system.

PMID- 8870832
TI  - Large, virus-like sinuous tubules in the endoplasmic reticulum of human neurons:
      report from a case of encephalopathy and brief critical review.
AB  - We report a case of a rapidly progressive, fatal non-inflammatory demyelinating
      disease, distinct from multiple sclerosis and lysosomal disorders, in a patient
      with progressive dementia. Electron microscopy of stereotactic brain biopsy
      samples revealed the presence in neurons of sinuous, double-walled cylindrical
      membranous structures within the cisterns of the endoplasmic reticulum. These
      structures were 75-80 nm in overall diameter, up to 1.5 mm long and had a 40- to
      45-nm diameter core. The possibility that they might be viruses of the
      Filoviridae or Paramyxoviridae families was considered, but the inclusions
      differed in key morphological aspects from members of both virus families and
      there were no supporting clinical or pathological data. Neither was it possible
      to assign the structures to any other known virus family on the basis of their
      morphology. Such inclusions have been the subject of only three published reports
      over the past 20 years. Evidence suggests that they may be confined to human
      central nervous system neurons, but occur in unrelated disorders (Alzheimer's
      disease, amyotrophic lateral sclerosis, meningoencephalitis, low-pressure
      hydrocephalus, demyelination). The possibility that they are formed in certain
      neurons by an abnormal internal budding process, as a response to a variety of
      pathological insults, is considered most likely, although an infectious origin
      (such as an unrecognised virus with variable clinical effect) cannot be ruled
      out.

PMID- 8870833
TI  - Chronic parasite infection in mice induces brain granulomas and differentially
      alters brain nerve growth factor levels and thermal responses in paws.
AB  - Schistosoma mansoni infection, both in humans and in animal models, is known to
      induce granulomas in the liver and intestine. It has also been reported that in
      humans the eggs of this parasite can reach the brain, causing psychiatric and
      neuropathological disorders. Whether this also occurs in rodents is unknown. To
      answer this question, mice were infected with this parasite and the central
      nervous system (CNS) examined at various time intervals. The results show that
      schistosomiasis induced granulomas in several regions of the CNS and increased
      nerve growth factor (NGF) levels in the cortex, hypothalamus and brain stem, but
      not in the hippocampus. The infection also caused paw hyperalgesia, as determined
      by the hot-plate test, and a local increase in NGF, but not in substance P. These
      findings indicate that the murine model of infection can be used for studying
      mechanisms leading to human neuroschistosomiasis and suggest that the
      neuropathological disorders and the sensory deficits observed in human
      schistosomiasis are associated with impaired levels of NGF in the peripheral and
      central nervous system.

PMID- 8870834
TI  - Immunohistochemistry of a cytoplasmic dynein (MAP 1C)-like molecule in rodent and
      human brain tissue: an example of molecular mimicry between cytoplasmic dynein
      and influenza A virus.
AB  - Immunohistochemistry with an antibody to influenza A/Aichi/2/68 (H3N2) virus was
      performed using normal mouse, rat and human brain tissues. Dot-like or
      filamentous structures in the neuronal cytoplasm were clearly stained. Axons were
      also stained, but weakly. Lewy bodies in Parkinson's disease substantia nigra
      were also positive. Immunoscreening of the antibody using mouse brain cDNA
      revealed that this antibody recognized the heavy chain of cytoplasmic dynein.
      Immunoblot analysis also showed that the reactive molecule was the same size as
      cytoplasmic dynein (microtubule-associated protein 1 C). This is an example of
      molecular mimicry between cytoplasmic dynein and influenza A virus, and the
      antibody appears to be useful for the localization on cytoplasmic dynein in the
      central nervous system.

PMID- 8870835
TI  - Alzheimer-type pathology in a patient with mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes (MELAS).
AB  - A 53-year-old Japanese woman with a point mutation in mitochondrial DNA
      (tRNALeu(UUR), nt3243) consistent with mitochondrial myopathy, encephalopathy,
      lactic acidosis and stroke-like episodes (MELAS) and Alzheimer-type brain
      pathology is reported. This woman had suffered myopathy and psychosis without any
      clinical evidence of, stroke-like episodes during the last 10 years of her life,
      and had died after an accident. At autopsy 30 h post mortem, a part of the brain
      was snap frozen for biochemical and histochemical studies, and the remaining part
      was processed for a routine examination and electron microscopy. In the brain
      there were no ischemic lesions. Instead, primitive/diffuse senile plaques were
      found throughout the brain, predominantly in the frontal and temporal lobes,
      while Alzheimer neurofibrillary tangles were found only in the parahippocampal
      gyrus. These plaques were positive for beta-protein and mostly negative for tau
      protein, ubiquitin, neurofilaments, alpha-choline acetyltransferase, and
      acetylcholinesterase. Mutations in codon 331 of the ND2 gene as well as codons
      693, 713 and 717 of the beta-amyloid precursor protein gene, known to be
      responsible for some cases of familial Alzheimer disease, were not found.
      Furthermore, coincidental Down syndrome was ruled out by chromosome analysis. The
      results suggest a possible correlation between this mitochondrial DNA abnormality
      and Alzheimer-type pathology.

PMID- 8870836
TI  - "Neuritic conglomerates" in the cerebral cortex of a patient with Creutzfeld
      Jakob disease.
AB  - In the cerebral cortex of a patient with Creutzfeld-Jakob disease (CJD), we found
      peculiar glomeruloid or skein-like structures which have not previously been
      described. The patient was a 67-year-old man, whose clinical features and
      neuropathological findings were consistent with CJD. The glomeruloid or skein
      like structures were distributed in the deep layers of the cortex and consisted
      of intricately entangled masses of thick argyrophilic fibers. These structures
      were immunostained with anti-neurofilament antibodies and were considered to have
      originated from neuronal cytoplasmic processes, most likely axons. The
      pathogenesis and pathological significance of these structures, which were
      tentatively termed "neuritic conglomerates," remains unclear. However they
      probably represent an overgrowth of the distal portion of axons and indicate the
      plasticity of the injured neurons.

PMID- 8870837
TI  - Suprachiasmatic nuclei lesions eliminate the group circadian rhythm of systolic
      arterial pressure but not of heart rate in rats.
AB  - The aim of this study was to evaluate the participation of the suprachiasmatic
      nuclei (SCN) in the generation and synchronization of cardiovascular rhythms.
      Seven sham-operated and 11 SCN-lesioned animals maintained under 12/12 hr
      light/dark cycle were used. Systolic arterial pressure (SAP) and heart rate (HR)
      were measured indirectly during 24-hour periods at 3-4 hour intervals. The data
      were analyzed using individual and group cosinor rhythmometry and Fourier
      analysis. A circadian rhythm of water intake was not detected in animals with
      successful SCN lesions. A reduction of the double amplitude/MESOR ratio for the
      24-hour component of drinking rhythm in the SCN-lesioned rats was observed. After
      SCN lesions the group 24-hour rhythm of SAP was eliminated while a significant
      group circadian rhythm for HR was detected. The individual amplitude/MESOR ratios
      for the 24-, 12-, 8- and 6-hour periodic components of SAP and HR in the lesioned
      rats showed no marked differences as compared with controls. The generation and
      entrainment of circadian variations in HR is probably not dependent on the
      integrity of SCN in rats. The SCN may participate in the entrainment of the
      circadian rhythm of SAP. The combination of completely abolished (water intake)
      and persisting (heart rate) rhythms further supports that the circadian
      regulatory system consists of a network of multiple oscillators.

PMID- 8870838
TI  - Vasopressin- and oxytocin-immunoreactive nerve cells in the aging rat
      hypothalamus.
AB  - Immunohistochemistry and morphometry were used to study the age-related changes
      in the vasopressin (AVP) and oxytocin (OXT) nerve cells in the paraventricular
      (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei of 3-, 11- and 28-month
      old rats. The results showed a statistically significant reduction in the mean
      number of AVP cells in the PVN, SON and SCN, and of OXT cells in the PVN with
      advancing age. Different age-related changes in the mean size of the
      immunoreactive cells were found in the three nuclei: a significant and transitory
      increase in the AVP and OXT cell sizes in the PVN, a tendency towards increasing
      the AVP and OXT cell sizes in the SON, and a significant and gradual decrease in
      the AVP cell size in the SCN. The combination of the morphometric data and
      staining patterns of the AVP and OXT perikarya and fibers in the PVN and SON
      pointed to an increased transport of AVP and OXT in 11-month-old rats as well as
      to a decreased production of these peptides in the PVN of 28-month-old rats.
      Taken together the staining pattern and the morphometric results showed a
      progressive loss of AVP cells in the SCN in aging.

PMID- 8870839
TI  - Morphological evidence for effects of the aging on the serotoninergic neurons in
      the rat brainstem nuclei.
AB  - The effects of age on the 5-hydroxytryptamine-immunoreactive (5-HT-IR) neurons in
      raphe and extrarapheal nuclei of rats were examined using morphometry.
      Quantitative parameters of the neuronal density and cross-sectional areas of the
      cell bodies as well as of the length and numbers of the processes of the 5-HT-IR
      neurons were analyzed in 3-, 12- and 26-month-old-rats. The results showed that
      aging affected the 5-HT-IR neurons in the rat brainstem nuclei. The age-related
      changes in the immunostaining pattern and quantitative parameters were more or
      less pronounced and earlier or later developed depending on the nucleus studied.
      It is most probably connected with specific functions and projections of each
      raphe nucleus.

PMID- 8870840
TI  - Effects of angiotensin II on brain monoamine oxidase activity in non-hypoxic and
      hypoxic mice.
AB  - The effects of angiotensin II (ATII) administered intracerebroventricularly
      (i.c.v.) at a dose of 0.5 microgram per mouse on the activity of monoamine
      oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in the forebrain of normoxic
      and hypoxic mice were studied. The influence of hypoxia (asphyctic and haemic) on
      MAO-A and MAO-B activity was also investigated. MAO-A activity was increased in
      haemic hypoxia; MAO-B activity increased in both asphyctic and haemic hypoxia.
      ATII increased MAO-A activity without affecting MAO-B activity under normoxic
      conditions. ATII increased MAO-A activity but decreased MAO-B in hypoxic
      (asphyctic) mice as compared to normoxic controls. The results suggest the role
      of MAO-A and MAO-B in the ATII-induced increase of susceptibility to acute
      hypoxia.

PMID- 8870841
TI  - The beta-chemokines, HIV type 1 second receptors, and exposed uninfected persons.

PMID- 8870842
TI  - HIV type 1 glycoprotein 120 amplifies tumor necrosis factor-induced NF-kappa B
      activation in Jurkat cells.
AB  - This article demonstrates that human immunodeficiency virus type 1 (HIV-1) gp120
      amplifies the activity of tumor necrosis factor alpha (TNF-alpha), a cytokine
      that stimulates HIV-1 replication through activation of NF-kappa B. In CD4
      positive Jurkat cells, gp120 potentiates TNF-induced NF-kappa B activation. TNF
      mediated activation of NF-kappa B is known to involve the intracellular formation
      of reactive oxygen intermediates (ROIs). Accordingly, we examined the influence
      of gp120 on the cellular redox state. We found that gp 120-modulated TNF-induced
      NK-kappa B activation was inhibited by the antioxidant butylated hydroxyanisole,
      indicating the involvement of redox-dependent mechanisms. In addition, we showed
      that gp120 induces intracellular formation of hydrogen peroxide, which is
      accompanied by a decrease in the ratio of glutathione to glutathione disulfide.
      In contrast, in the p56lck-deficient J.CaM1.6 T cell line, a derivative of the
      Jurkat cell line, gp120 was unable to stimulate hydrogen peroxide, to decrease
      the ratio of GSH to GSSG, and has no effect on TNF-induced NF-kappa B activation.
      This demonstrated that p56lck protein tyrosine kinase plays an active role in
      transmitting a signal that increases the oxidative state of the cell and as a
      consequence amplifies TNF-mediated NF-kappa B DNA binding. We have demonstrated
      that Tat protein decreased both the Mn-dependent superoxide dismutase (MnSOD) and
      the cellular glutathione content (GSH). Here we show that, in contrast to Tat,
      gp120 is unable to inhibit activity and expression of MnSOD and to decrease GSH
      content. Taken together, our data suggest that gp120 potentiates TNF-induced NF
      kappa B activation by stimulating a signal pathway that involves p56lck and the
      increased formation of reactive oxygen intermediates such as H2O2. These findings
      may be relevant for the regulation of HIV-1 replication in T cells.

PMID- 8870843
TI  - HTLV type IIIB infection of human thymic epithelial cells: viral expression
      correlates with the induction of NF-kappa B-binding activity in cells activated
      by cell adhesion.
AB  - Productive infection by the LAV strain has been demonstrated in T cell precursors
      at different stages of intrathymic development, while viral replication in thymic
      epithelial cells is still controversial. In this article we show that epithelial
      cell cultures derived from the medullary component of normal thymus are
      infectable by HTLV-IIIB virus through cell-free and lymphoid-mediated
      transmission. Free virus inoculum results in the integration of proviral copies
      undergoing poor replication, whereas lymphoid-mediated transmission leads to
      substantial viral expression and the production of viral progeny able to
      secondary infect lymphoid cells. Interleukin 6 production and phenotype changes
      (increased expression of MHC class I and ICAM-1) were induced in TE cells by
      contact with free virus or by adhesion to infected lymphoid cells. By contrast,
      NF-kappa B-binding activity on the HIV-1 LTR kappa B enhancer element was
      upregulated only by contact with infected lymphoid cells, but not with virus. The
      viral replication observed in TE cells after lymphoid-mediated transmission
      correlates with the upregulation of NF-kappa B-binding activity. Interleukin 6
      increased production and phenotype changes and increased NF-kappa B-binding
      activity were also induced by adhesion to uninfected lymphoid cells,
      demonstrating that lymphoepithelial cell contacts can activate TE cells. These
      results demonstrate that thymic epithelial cells are permissive to HIV infection
      and that viral replication in this cell lineage can be modulated by intracellular
      signals delivered by adhesive contacts.

PMID- 8870844
TI  - The inhibition of HIV replication in monocytes by interleukin 10 is linked to
      inhibition of cell differentiation.
AB  - The effect of exogenous recombinant interleukin 10 on the replication of low
      passage HIV-1 strains in blood-derived monocytes and monocyte-derived-macrophages
      (MDMs) was examined at various stages of cell maturation after adherence to the
      plastic substrate. Interleukin 10 inhibited extracellular production of HIV-1 to
      a greater degree in monocytes infected within 24 hr of adherence than those
      infected at 5-7 days. Inhibition of viral production as extracellular p24 antigen
      was most marked when interleukin 10 was preincubated with monocytes for 24-96 hr
      (optimum, 48 hr), and increased between 2 and 100 ng/ml. Neutralizing antibody to
      IL-10 reversed the inhibition. Inhibition of HIV production from monocytes and
      macrophages was maximal at 1 week after a single addition of cytokine, but then
      HIV production rose to control levels. Interleukin 10 was also found to inhibit
      reversibly the normal increase in size and maturation of both uninfected and HIV
      infected monocytes during 10-15 days of adherence. In addition, cytoplasmic and
      membrane expression of CD26, a marker of macrophage maturation, was markedly
      inhibited but the proportion of detaching, apoptotic, or necrotic cells was also
      not increased. Hence, interleukin 10 reversibly inhibits both monocyte maturation
      and HIV production from infected monocytes with similar kinetics, suggesting that
      inhibition of monocyte maturation by IL-10 may have a marked effect of HIV
      production by these cells.

PMID- 8870845
TI  - Inhibition of human immunodeficiency virus replication in differentiating
      monocytes by interleukin 10 occurs in parallel with inhibition of cellular RNA
      expression.
AB  - The mechanism of inhibition of HIVBa-L replication by interleukin 10 (IL-10) in
      primary monocytes and macrophages at various stages of maturation was
      investigated using semiquantitative PCR for reverse-transcribed HIV DNA, and
      Northern hybridization for HIV mRNA expression in comparison with extracellular
      p24 antigen. Pretreatment of monocytes with IL-10 markedly inhibited expression
      of both unspliced and spliced HIV RNA, reaching a nadir at 7 days and recovering
      to normal levels by 10 days after a single application. The optimum inhibitory
      concentration was 25 ng/ml. Less inhibition of HIV RNA expression was observed
      when IL-10 was added after HIV infection of monocytes and the inhibitory effect
      progressively declined to negligible levels as monocytes matured into macrophages
      over 10 days. IL-10 also downregulated the expression of cellular genes,
      including the transferrin receptor, 28S rRNA, and GAPDH. The kinetics of the
      inhibition of cellular mRNAs correlated with the inhibition of HIV RNA and also
      declined as monocytes matured into macrophages. In contrast, IL-10 did not
      inhibit cellular mRNA expression in the macrophage cell line THP-1. Neutralizing
      polyclonal antibody to IL-10 reversed all its inhibitory effects. Interaction of
      IL-10 and TNF-alpha in combination were generally antagonistic in their effects
      on HIV transcription. IL-10 prevented stimulation of HIV RNA expression by TNF
      alpha after preincubation with monocytes for 48 hr. IL-10 had no effect on the
      levels of HIV cDNA or the process of initiation and completion of reverse
      transcription. The inhibitory effect of IL-10 on HIV replication in maturing
      monocytes was probably mediated mainly by inhibition of cellular gene expression
      and inhibition of maturation of monocytes into macrophages and their activation,
      with consequent downregulation of HIV mRNA.

PMID- 8870846
TI  - HIV type 1 phenotype correlates with the stage of infection in vertically
      infected children.
AB  - A cohort of 39 vertically infected children (class N, A, B, and C of the CDC HIV
      classification for pediatric infection) was studied by virus isolation and non
      syncytium inducing (NSI)/syncytium inducing (SI) HIV-1 phenotype evaluation. The
      HIV-1 isolates were recovered from PBMCs and the MT-2 cell line was used to
      perform the syncytium assay. HIV-1 could be isolated in 34 of 39 (87%) infected
      children, regardless of the clinical and immunological stage of the disease.
      Class N and A subjects harbored exclusively NSI strains, whereas the SI phenotype
      was detected in two of eight class B and five of nine class C patients. All of
      the SI variants were observed in severely CD4-depleted children (class 3
      patients). The capability of pediatric HIV-1 isolates to induce a cytopathic
      effect is associated with the clinical status and the degree of CD4 depletion.
      These data suggest that the biological properties of HIV-1 isolates in children
      do not differ from those observed in adults, and that viral phenotype strictly
      correlates with disease progression in vertically infected children.

PMID- 8870847
TI  - Virologic and immunologic markers of disease progression in pediatric HIV
      infection.
AB  - Correlates of progression of human immunodeficiency virus (HIV) infection to AIDS
      include the reduction in CD4+ T cells and the emergence of syncytium-inducing
      (SI) HIV variants. It has been suggested that progressive defects in interleukin
      2 (IL-2), IL-12, and IFN- gamma production (type 1 cytokines), and increased
      production of IL-4 (and of IL-4-driven hyper-IgE), IL-6, and IL-10 (type 2
      cytokines), could provide another correlate of disease progression. To determine
      the possible association among these markers, viral phenotype, cytokine
      production, IgE serum concentration, and rate of CD4 depletion were analyzed in a
      cohort of vertically HIV-infected children. We report that significantly higher
      production of type 2 cytokines and augmented IgE concentration are observed in
      children in whom HIV SI is isolated. In addition, we observed that the isolation
      of HIV SI and the production of high quantities of type 2 cytokines are
      correlated with increased loss of CD4 T cells in the 12 months preceding the
      determinations. These data suggest that the virologic and immunologic parameters
      characteristic of advanced HIV infection may be associated in pediatric HIV
      infection, and indicate a virologic-immunologic pathogenesis leading to the
      appearance of AIDS.

PMID- 8870848
TI  - Cytokine mRNA expression in mononuclear cells from different tissues during acute
      SIVmac251 infection of macaques.
AB  - We used semiquantitative RT-PCR to monitor the expression of mRNA encoding
      cytokines (IL-1 beta, IL-6, TNF-alpha, and IL-10) and IFN-gamma in fresh isolated
      peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs),
      and mononuclear cells obtained after bronchoalveolar lavages (BALMCs), of four
      cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian
      immunodeficiency virus (SIVmac251). To investigate the effects of the viral load
      on the expression of the cytokines, two monkeys received 30 mg kg-1 day-1 of
      didanosine (ddI). The two nontreated monkeys became infected and seroconverted,
      whereas the ddI-treated monkeys were completely protected as demonstrated by all
      criteria of diagnosis of SIV infection. Concomitant with the peak of viral
      replication (2 weeks after the experimental inoculation), high levels of IL-6
      mRNA were produced in PBMCs, LNMCs, and BALMCs of the two placebotreated infected
      monkeys. Overexpression of TNF-alpha and IL-10 mRNAs was sometimes observed in
      LNMCs and BALMCs. A progressive overexpression of IFN-gamma mRNA, starting 2
      weeks after experimental inoculation, was observed in BALMCs from infected
      animals. Concurrently, a marked increase in the CD8+ lymphocyte percentage in the
      BAL fluids was detected by FACS analysis. Thus, our results emphasize the
      importance of a comparative study of the expression of cytokines in different
      tissues. They suggest the interactions of monocyte/macrophage monokine production
      with viral replication, as well as the role of IFN-gamma in the development of
      lung cellular immunity to SIV infection.

PMID- 8870849
TI  - The relationship between the interferon alpha response and viral burden in
      primary SIV infection.
AB  - The interferon alpha (IFN-alpha) response of rhesus macaques was investigated
      during primary infection with pathogenic and attenuated simian immunodeficiency
      virus (SIV). IFN-alpha was detected in the serum of animals as early as day 4
      after inoculation of SIVmac251, but remained barely detected in animals infected
      with the attenuated virus SIVmac251 delta nef. The peak of IFN-alpha secretion
      preceded that of antigenemia in animals infected with pathogenic virus,
      indicating that the IFN-alpha response did not prevent viral spread. In addition,
      elevated levels of IFN-alpha in the serum after the acute stage of infection was
      associated with persisting antigenemia. The analysis of lymph nodes (LNs) by in
      situ hybridization showed that, similar to the results obtained with peripheral
      blood, the induction of IFN-alpha in lymphoid organs was rapidly detected in
      animals infected with the pathogenic virus, but remained very limited in animals
      infected with the attenuated virus. Quantitation of the hybridization signal
      indicated that IFN-alpha-producing cells were numerous in the LNs of animals that
      had a high viral burden. Taken together, these findings indicate that the IFN
      alpha response is unable to contain the initial burst of SIV replication.

PMID- 8870850
TI  - Diversity of antibody binding to V3 peptides representing consensus sequences of
      HIV type 1 genotypes A to E: an approach for HIV type 1 serological subtyping.
AB  - We investigated whether V3-binding assays might be useful to analyze human
      immunodeficiency virus type 1 (HIV-1) variants in different geographic regions.
      We showed that strong cross-reactivity between subtype-specific V3 peptides is
      almost inevitable in standard indirect enzyme-linked immunosorbent assays (EIA),
      impairing precise serological subtyping. We therefore developed a subtype
      specific EIA (HIV-1 SSEIA) that uses the principle of blocking by an excess of
      peptide in the liquid phase. Using 231 serum samples collected from HIV-1
      infected individuals in 10 different geographical areas from 4 continents, we
      showed that this approach detected the dominant subtype reactivity in more than
      97% of the cases. Internal controls (0 and 100% blocking) were used for every
      sample such that comparative analysis was possible, independent of both the
      individual humoral response and the time of collection during the course of
      infection. This was validated by the excellent concordance of the serological
      profiles of couples and the temporal stability of the serological profile in
      individuals. The geographical distribution of the various subtypes in the SSEIA
      was in agreement with the present knowledge of the distribution of the various
      genotypes. Although the goal of this study was not an extensive
      seroepidemiological survey, our results showed that the various profiles in most
      of the regions were relatively homogeneous, but in central Africa there was a
      large diversity of serological profiles. Cluster analysis identified a limited
      number of V3 serogroups of serotypes within the HIV-1 group M. Five serogroups,
      some of them divided into subgroups, were identified and characterized by a mean
      serological profile. Our data confirmed that subtypes A and C, although being
      dissimilar genetic subtypes, present conserved antigenic properties in the V3
      region, and that the D subtype is probably the most divergent within the group M
      (B Korber et al., J Virol 1994;68:6730). Cluster analysis showed a clear
      correlation between position within the dendrogram and geographical origin of the
      samples. This is further support for the reliability and thereof the usefulness
      of the SSEIA. This simple methodology may help facilitate the analysis of the
      distribution of various HIV-1 subtypes circulating in different populations and
      regions.

PMID- 8870851
TI  - Lack of dual HIV infection in a transfusion recipient exposed to two seropositive
      blood components.

PMID- 8870852
TI  - Fluctuating diversity in the HTLV-IIIB virus stock: implications for
      neutralization and challenge experiments.

PMID- 8870853
TI  - Doing more with less.

PMID- 8870854
TI  - How to withdraw mechanical ventilation: more studies are needed.

PMID- 8870855
TI  - Allocation of scarce resources: ethical challenges, clinical realities.

PMID- 8870856
TI  - Procedures used in withdrawal of mechanical ventilation.
AB  - OBJECTIVE: The purpose of this study was to describe ways in which withdrawal of
      mechanical ventilation is carried out in one institution, patient responses to
      the various methods of withdrawal, and nurses' perceptions of the methods and
      morality of ventilator withdrawal. METHOD: A retrospective descriptive study was
      used with a convenience sample of adult patients who underwent terminal weaning
      at University Hospitals of Cleveland. Demographic and clinical data, and
      descriptions of the exact method of ventilator withdrawal were collected from the
      medical records of these patients. The nurse caring for the patient was
      interviewed about his or her perceptions, within 7 days of the withdrawal.
      RESULTS: Data were obtained on 42 subjects. There were no differences in mental
      status, ventilatory status, age, or duration of survival between the patients who
      had support removed gradually and those from whom it was abruptly removed.
      Morphine was administered to 88% of the sample during withdrawal. Survival
      duration was unrelated to morphine dosage, but did correlate with ventilatory
      status at the time of withdrawal. Every nurse interviewed reported that he or she
      believed the act of withdrawal for that patient was morally correct, although
      only 85% were completely comfortable with carrying out the procedure.
      CONCLUSIONS: These results provide a foundation for preliminary recommendations
      about the most humane form of ventilator withdrawal and the appropriate use of
      narcotics and sedatives during withdrawal.

PMID- 8870857
TI  - Impact of patient consciousness on the intensity of the do-not-resuscitate
      therapeutic plan.
AB  - BACKGROUND: The nature and intensity of a do-not-resuscitate therapeutic plan
      varies by patient. Some do-not-resuscitate therapeutic plans may include
      interventions directed at the withdrawal of life-sustaining therapy. OBJECTIVE:
      The purpose of this study was to examine the impact of patient consciousness on
      the nature and intensity of the do-not-resuscitate plan, and on the decision to
      withdraw life-sustaining therapy. METHODS: This study represents a secondary
      analysis of data obtained in a previous study to evaluate patient care
      requirements under varying intensities of do-not-resuscitate plans. Data were
      collected retrospectively through record review. Patients were grouped as
      follows, according to the intensity of the do-not-resuscitate plan: (1) all but
      cardiopulmonary resuscitation, (2) conservative care without cardiopulmonary
      resuscitation, (3) comfort only, and (4) withdrawal of life-sustaining therapy.
      In addition to demographic data, consciousness and illness severity were
      measured. Data were analyzed using descriptive statistics. RESULTS: There was a
      significant decrease in consciousness from admission in all groups except
      conservative care. The withdrawal group had the lowest average Glasgow Coma Scale
      scores at the time of the do-not-resuscitate designation. Multiple regression
      analysis was used to demonstrate a significant impact of consciousness on type of
      do-not-resuscitate decision, but no significant impact from age or illness
      severity. CONCLUSIONS: These results support previous observations that decisions
      to withdraw life-sustaining therapy are prompted by diminished consciousness.
      These results may stimulate caregivers to offer withdrawal of life-sustaining
      therapy as an option in patients with severely decreased consciousness and a poor
      prognosis for functional recovery.

PMID- 8870858
TI  - Facilitating the recovery of open heart surgery patients through quality
      improvement efforts and CareMAP implementation.
AB  - OBJECTIVE: To illustrate, using a literature review and CareMAPs, how care
      coordination and implementation of standard protocols can impact clinical
      outcomes for open heart surgery patients. METHODS: A CareMAP for open heart
      surgery patients was developed by a multidisciplinary team. To evaluate the
      effectiveness of CareMAP implementation and specific quality improvement efforts,
      a pilot study was done that focused on increasing activity levels, decreasing
      ventilator time, and decreasing the frequency of arterial blood gas sampling for
      a sample of 55 open heart surgery patients. A rapid recovery program was
      developed based on the results of this pilot study. A multidisciplinary
      continuous quality improvement team was developed to focus on three primary
      areas: ventilator weaning time, activity regimens, and early transfer to the open
      heart surgery step-down unit. Forty-nine open heart surgery patients were
      included in the initial program evaluation. RESULTS: The frequency of arterial
      blood gas sampling decreased from an average of 5.8 per patient to an average of
      3.9 per patient. Postoperative length of stay also decreased by 1.3 days for
      diagnosis related group 106 patients, and 3.7 days for diagnosis related group
      107 patients. Results of the pilot study demonstrated additional opportunities
      for improving the care of open heart surgery patients. Using the rapid recovery
      program, the average ventilator time decreased by 4.4 hours per patient. The
      average postoperative length of stay decreased to 4.7 days. CONCLUSIONS: Through
      the quality improvement process and through the use of CareMAPs and specific
      protocols, the recovery of open heart surgery patients was facilitated.

PMID- 8870859
TI  - Critical care outcomes: linking structures, processes, and organizational and
      clinical outcomes.
AB  - BACKGROUND: Organizational structure and process are thought to affect patient
      care outcomes beyond the effects of expert clinical care. OBJECTIVES: To test the
      hypothesis that a discretionary pattern of organizational structure and process
      factors is predictive of critical care unit performance, ie, desirable patient
      and organizational outcomes. METHODS: Quality-of-care patient and organizational
      outcomes were evaluated in 25 critical care units. A single value representing
      each critical care unit's euclidian distance from a theoretically ideal pattern
      of discretionary function was determined and correlated with unit-level measures
      of outcomes (standardized mortality ratio, severity-adjusted length of stay,
      patient satisfaction, quality of nursing care, and nursing retention). RESULTS:
      Distance from the ideal-type discretionary pattern predicted organizational but
      not clinical outcomes. Units closer to the ideal-type pattern had higher RN
      retention, and were viewed as better places to work, with higher-quality care by
      both nurses and physicians. Objectively measured quality of care, patient
      satisfaction, severity-adjusted mortality, and length of stay were not
      consistently related to better-structured units. CONCLUSIONS: With experienced
      critical care practitioners, unit-level structure and process factors were better
      predictors of organizational outcomes than of clinical outcomes.

PMID- 8870861
TI  - Clinical presentation of cardiac herniation without lung resection: a surgical
      emergency.

PMID- 8870860
TI  - Lung transplant rejection: obliterative bronchiolitis.
AB  - BACKGROUND: More centers are performing lung transplants for a variety of
      pulmonary conditions. Chronic rejection, manifested as obliterative
      bronchiolitis, is the most common cause of late death (greater than 6 months
      after transplant) in this population. OBJECTIVES: To review published literature
      on obliterative bronchiolitis to determine the current terminology and
      definition, pathophysiology, incidence, diagnosis, treatment, and outcome of this
      condition. DATA SELECTION: A MEDLINE search was done using the medical subject
      headings of bronchiolitis obliterans and lung transplantation. Studies were
      selected based on sample size and reporting of obliterative bronchiolitis
      statistics. Sources that were not data-based discussions also were selected if
      they were comprehensive reviews or provided insight into relevant issues.
      SUMMARY: Obliterative bronchiolitis terminology is not used consistently in the
      literature. It is an obstructive defect that affects the airways, causing
      progressive occlusion. Diagnosis is based on clinical findings or on histological
      analysis; early markers are sought, to aid in diagnosis. Incidence of
      obliterative bronchiolitis varies from 7% to 54%, with a mortality rate of 30% to
      40%. Currently, enhanced immunosuppression is the treatment of choice, although
      research is being carried out to evaluate methods of inhibiting growth factor
      activity for use in future treatment strategies. CONCLUSIONS: Obliterative
      bronchiolitis is a common complication in lung transplant recipients, and future
      research will focus on treatment and early diagnosis. Efforts are under way to
      standardize nomenclature and reporting of incidence and mortality rates.

PMID- 8870862
TI  - Emergent intubation of the difficult pediatric airway using the laryngeal mask
      airway.

PMID- 8870864
TI  - Nurses and euthanasia: a tale of two studies.

PMID- 8870863
TI  - Atrial fibrillation: an increasingly common and provocative arrhythmia.

PMID- 8870865
TI  - The life and work of Erik M. P. Widmark.
AB  - Erik M. P. Widmark (1889-1945) was among the first researchers to study in a
      systematic way the absorption, distribution, and elimination of ethanol in the
      body; in addition, he formulated his results in mathematical terms. Widmark's
      research during the first decades of this century paved the way for innovative
      traffic safety legislation that stipulated punishable limits of alcohol in the
      blood of a person driving a car. The 50th anniversary of Widmark's death was
      commemorated in 1995. His contributions have gained enormous respect and are
      still widely cited in forensic science, especially in connection with the crime
      of driving under the influence of alcohol. The Widmark equations and the factors
      beta and r are now part of the vocabulary of all those trained in forensic
      alcohol analysis and toxicology.

PMID- 8870866
TI  - Frequency of throat-skeleton fractures in hanging.
AB  - A total of 109 cases of suicidal or accidental hanging were evaluated and the
      number of hyoid bone or thyroid cartilage fractures or both was investigated in
      relation to the highest point of the ligature mark. In 73 cases (67%), at least a
      single fracture of the throat skeleton was detectable, and the youngest
      individual with positive findings was aged 14 years. In 28 of the 73 positive
      cases (38%), a single fracture was found, whereas 27 individuals (37%) showed a
      twofold injury. Three fractures of the throat skeleton were observed in 11 cases
      (15%), and in seven individuals (10%), all the horns of the hyoid and thyroid
      cartilage were broken. The youngest individual with four fractures was 28 years
      old (elastic non-ossified throat skeleton). Even though a higher incidence of
      positive results and in particular of multiple fractures could be established in
      cases with a highest point of the ligature mark at or behind the ears, no clear
      correlation between frequency and number of throat-skeleton fractures was
      detectable in our series.

PMID- 8870867
TI  - Left ventricular aneurysm caused by blunt chest trauma.
AB  - A case of unexpected death associated with an aneurysm of the left ventricle
      caused by nonpenetrating chest trauma is described. A review of the more recent
      literature on the incidence, pathological course, and prognosis of the
      posttraumatic ventricular aneurysm pointed out the necessity of suspecting
      cardiac damage in cases of blunt chest trauma especially when major injuries may
      obscure heart involvement.

PMID- 8870868
TI  - Injury of the tunica media in fatal rupture of the vertebral artery.
AB  - The histologic findings in seven cases of traumatic basal subarachnoid hemorrhage
      from rupture of a vertebral artery are reported. In all cases, blows to the head
      or neck resulted in minor injury to the cranial or cervical soft tissues but the
      ipsilateral intracranial segment of the vertebral artery was the site of a
      longitudinal transmural tear. In addition to rupture, the arterial wall proximal
      and distal to the site of rupture showed evidence of distortional injury of the
      tunica media. These traumatic lesions appeared as patchy anuclear regions of the
      media with distinctive pallor of smooth muscle staining. We propose that the
      forces which cause vertebral artery rupture stretch the artery along its long
      axis, thereby distorting the artery leading to this characteristic histologic
      change.

PMID- 8870869
TI  - Deaths of infants on polystyrene-filled beanbags.
AB  - We have reviewed 35 deaths of infants who were found face down on polystyrene
      filled beanbags or their equivalents. Most of the deaths were recorded as sudden
      infant death syndrome. One-half of the children died before the age of 2 months.
      It is suggested that the bags played a major factor in the babies' deaths and are
      dangerous for young children. Mechanisms involved in the deaths of infants on
      beanbags may also be applicable to deaths of infants on other types of bedding.

PMID- 8870870
TI  - Nineteenth-century Massachusetts coroner inquests.
AB  - Coroner is an ancient office, dating back centuries in England; originally
      financial officers, coroners over time become medicolegal investigators. Coroners
      in early Massachusetts functioned under English common law and, later, under
      statute. However, studies of early coroners and inquests are not common, and many
      details of how coroners actually functioned are unknown. A previously unpublished
      set of 19th-century Massachusetts inquest records discloses details of coroner
      function, including administrative and financial details, social conditions
      surrounding inquests, and increasing use of medical and toxicologic testimony.

PMID- 8870871
TI  - Ambulatory monitoring devices and the forensic autopsy.
AB  - Ambulatory monitoring devices (AMDs) such as Holter (ECG) and apnea (respiratory)
      monitors with built-in date- and time-correlated memories are occasionally
      encountered in the forensic autopsy. Diagnostic data are usually readily obtained
      by returning the device to the hospital department or rental company. This data
      can be easily correlated with autopsy findings to arrive at surprisingly precise
      conclusions in some cases. We present two illustrative cases: an elderly man
      wearing a Holter monitor who shot himself in the mouth with a shotgun, and a 15
      month-old oxygen-dependent prematurely born boy with bronchopulmonary dysplasia
      whose apnea monitor had been turned off 5 days before he died of
      bronchopneumonia. We discuss other kinds of AMDs that may be encountered in the
      forensic autopsy and suggest that information from these monitors perhaps should
      become part of the forensic autopsy report.

PMID- 8870872
TI  - Postmortem cranial MRI and autopsy correlation in suspected child abuse.
AB  - We investigated the correlation between postmortem magnetic resonance imaging
      (MRI) of the head and autopsy findings in suspected child abuse. Postmortem MRI
      was performed within 24 h of death and before autopsy in 11 children 2 years old
      or younger whose deaths were unexplained or suspected to be due to child abuse.
      MRI findings were available to the pathologist at the time of autopsy. In eight
      cases of death from non-accidental trauma, cerebral edema, contusion, shearing
      injury, ischemia, and infarction were well demonstrated on MRI. In the three
      deaths determined not to be due to trauma, there were no false-positive MRI
      findings. Autopsy was superior in detection of subarachnoid hemorrhage, suture
      separation, extracranial injuries, and very small subdural hematomas. MRI
      findings were useful in directing the autopsy and brain-cutting to focal areas of
      abnormality. Postmortem MRI and autopsy are complementary, and each may disclose
      abnormalities missed by the other. In half of the eight cases of child abuse
      examined, the combination of MRI and autopsy added valuable information compared
      with the results of autopsy alone. Postmortem MRI can be a valuable addition to
      autopsy findings in the investigation of fatalities potentially due to child
      abuse.

PMID- 8870873
TI  - Postmortem coronary subtraction angiography.
AB  - Thorough examination of the coronary arteries is essential when performing
      medicolegal autopsies. In some cases, evaluation is optimized by using postmortem
      angiography before dissection. Unfortunately, most techniques are far too time
      consuming to be readily employed by forensic pathologists. We describe a simple
      technique of "subtraction angiography" that provides valuable information in a
      timely manner in cases that can benefit from postmortem angiographic analyses. We
      find the technique particularly helpful in cases that have had invasive coronary
      artery procedures contemporaneous with death.

PMID- 8870874
TI  - A case of lethal intoxication after ingestion of toquilone compositum.
AB  - A case of acute intoxication of both methaqualone and diphenhydramine is
      reported. The analysis of these compounds was performed by liquid-liquid
      extraction (Toxi-Lab DPC procedure) followed by gas chromatography/mass
      spectrometry determination; both substances are contained in the pharmaceutical
      formulation called Toquilone Compositum (Medichemie, Switzerland).

PMID- 8870875
TI  - The Abbreviated Injury Scale. A valuable tool for forensic documentation of
      trauma.
AB  - Anatomic trauma scoring systems are fundamental to trauma research. The
      Abbreviated Injury Scale (AIS) and its derivative, the Injury Severity Score
      (ISS), are the most frequently used scales. We assessed the applicability of the
      AIS and the ISS systems for postmortem forensic documentation of trauma. In a
      prospective study, all trauma autopsies performed between January 1 and June 30,
      1993, were coded according to the AIS and ISS method. All cases were reviewed by
      a consultant in forensic medicine and a traumatologist. Cases were grouped in
      three categories according to ISS values: 0-14, 16-66, and 75. These categories
      represent minor, major, and incompatible-with-life injuries, respectively. All
      autopsy findings in which ISS was < or = 14 were peer-reviewed to establish
      mechanism and cause of death. In the 6-month period, 279 trauma-related autopsies
      were studied. Age at death averaged 37.1 +/- 18.7 (mean +/- SD). Eighty-six
      percent of the victims were male. Penetrating trauma was the mechanism of injury
      in 67%. ISS was 0-14 in 19 cases, 16-66 in 150 cases, and 75 in 110 cases. In
      conclusion, AIS and ISS scoring systems are applicable to trauma forensic
      documentation. Using these methods for coding postmortem findings may help in
      establishing a database for trauma research, and this information could
      constitute a major part of continuous quality improvement of trauma management.
      Low ISS values may serve as a warning, sometimes indicating preventable death.

PMID- 8870876
TI  - Factors affecting the rate and pattern of the first costal cartilage
      ossification.
AB  - In the present study, the extent of costochondral ossification of the first rib
      was determined from 78 chest roentgenograms of 13 healthy male soldiers subjected
      to a periodic follow-up. Roentgenography was performed at a mean interval of 2.9
      years over a 15-year period. Mean subject age was 24 years at the commencement of
      the study and 37 years at its termination. Our results show that ossification of
      the first costal cartilage may start early in adult life and progress at
      individual rates. The ossification process proceeded from the costal toward the
      sternal end of the cartilage in an anteromedial direction. The morphological age
      related changes ranged from the formation of small osseous islands in the
      cartilage to a complete ossification between the first rib and the sternum. The
      main conclusion of the study is that the degree of ossification of the first
      costal cartilage as an indicator of age does not provide the precision necessary
      for anthropological or forensic studies.

PMID- 8870877
TI  - Cerebral amyloid angiopathy. A review.
AB  - Cerebral amyloid angiopathy (CAA) is a condition characterized by amyloid
      deposition in cerebral blood vessels. It occurs most frequently in association
      with clinical Alzheimer's disease but also occurs in some nondemented elderly
      people. CAA is a cause of spontaneous cerebral hemorrhage and may therefore
      present as a sudden unexpected death in an elderly person. The amyloid is
      deposited in cortical blood vessels, and on hematoxylin-eosin sections takes the
      form of pink hyaline thickening of arteries and arterioles, often with narrowing
      of the lumina. For diagnosis apple-green birefringence after Congo red staining
      is the most widely practiced and reliable tool. CAA-related hemorrhage may also
      occur in any lobe of the cerebrum close to the external surface and may occur at
      multiple sites and at the same or different times. CAA-related hemorrhage may
      occur in the setting of trauma necessitating distinction between the two and
      raising the question of whether it precipitated trauma or vice versa. Usually CAA
      related hemorrhage is infrequent in sites where traumatic hemorrhages occur, and
      traumatic hemorrhages are often associated with other hemorrhages in sites
      typical for trauma. Five cases demonstrating many of the clinical and
      pathological features of CAA-related hemorrhage are presented. In two of the five
      cases, the hemorrhage followed trauma, suggesting that trauma as a precipitating
      factor for CAA-related hemorrhage may be more common than is generally
      recognized. CAA-associated hemorrhage should be considered in the differential
      diagnosis of cerebral hemorrhage in the elderly whether or not dementia is
      present.

PMID- 8870878
TI  - Diagnostic difficulties in cases of sudden death in infants with mandibular
      hypoplasia.
AB  - Infants with mandibular hypoplasia are at risk of sudden death from
      cardiorespiratory arrest secondary to upper airway obstruction. To evaluate
      diagnostic difficulties that may occur at autopsy in such infants, the autopsy
      files at the Adelaide Children's Hospital (ACH) for 36 years, 1959 to 1994, were
      reviewed. Eight cases were identified (age range, 2 days to 10 months; mean age,
      2.2 months; male/female ratio, 5:3). In all cases, death was considered most
      likely due to airway obstruction related to mandibular hypoplasia or its
      treatment. Although death occurred in the hospital in five cases, one infant
      suddenly collapsed at home while feeding and died, and two infants were
      unexpectedly found dead in their cribs at home. Three infants had defined genetic
      syndromes. Although all the infants had histories of antemortem airway
      obstruction, one infant had normal oxygen saturation studies before hospital
      discharge, and one infant had a tracheostomy. Acute bronchopneumonia was an
      exacerbating factor in one case. Assessment of mandibular size is important in
      any infant who dies unexpectedly; and if hypoplasia is found, careful review of
      the clinical details for evidence of airway obstruction is necessary to help
      distinguish these cases from sudden infant death syndrome (SIDS). Sudden death
      may, however, occur in infants with mandibular hypoplasia in spite of apparent
      clinical stability before death with no significant recent episodes of oxygen
      desaturation.

PMID- 8870879
TI  - Mechanisms of sudden death and autopsy findings in patients with Arnold-Chiari
      malformation and ventriculoatrial catheters.
AB  - Neurological and vascular complications of Arnold-Chiari malformation treated
      with ventriculoatrial shunting may result in sudden or unexpected death. Two
      patients with Arnold-Chiari malformation and ventriculoatrial shunting had
      variable clinical manifestations and diagnostic difficulties. A 3-year-old girl
      with a 1-day history of right-sided heart failure died unexpectedly soon after
      cardiac catheterization. At autopsy examination an adherent thrombus around the
      ventriculoatrial catheter tip, pulmonary infarction, and embolic pulmonary
      arterial hypertensive changes were found. In the second case, a 21-year-old man
      died suddenly after a brief episode of dyspnea. He had a 1-year history of
      "asthma" before death. Autopsy examination confirmed pulmonary infarction and
      embolic pulmonary arterial hypertensive changes. There was no histological
      evidence of asthma. Deaths in both cases were due to pulmonary infarction
      stemming from thromboemboli derived from ventriculoatrial catheterization. Both
      patients had evidence of long-standing clinically unsuspected vascular disease,
      which may have contributed to death. Cardiac catheterization may also have
      precipitated death in the first patient. Other possible problems leading or
      contributing to sudden death in such patients include pulmonary hypertension with
      chronic cor pulmonale, airway obstruction from recurrent laryngeal nerve
      paralysis, and shunt blockage with acute hydrocephalus. Lethal brainstem
      compression may also accompany relatively minor trauma associated with chronic
      cerebellar tonsillar herniation in these patients.

PMID- 8870880
TI  - Fatal fat embolism in acute hepatic necrosis with associated fatty liver.
AB  - We report two cases of generalized nonviolent hepatogenic fat embolism. A 63-year
      old woman was sent to the hospital with suspected mushroom poisoning. Shock
      symptoms occurred quickly and could not be treated effectively; the patient died
      24 h after admission. Postmortem examination showed acute yellow dystrophy of the
      liver with a severe preexisting fatty liver. Any intoxication including Amanita
      phalloides could be excluded. In all probability, a fulminant viral hepatitis
      caused liver dystrophy, and the decay of the fatty liver cells led to generalized
      fat embolism as the cause of death. The second patient, a 46-year-old man, was
      reported to have suffered from an acute illness while in prison and died after
      having been transferred to the local hospital. Histological examinations showed
      an acute liver dystrophy probably caused by fulminant viral hepatitis with fatty
      degeneration. In this case, the cause of death was also found to be generalized
      fat embolism.

PMID- 8870881
TI  - The definition of "sudden" in SIDS.

PMID- 8870882
TI  - Study addresses question of preferred initial therapy for depression.

PMID- 8870883
TI  - Cancer risk with calcium-channel-blocker use examined.

PMID- 8870884
TI  - Monitoring but no drug-regimen changes advised for hemophilia patients taking
      protease inhibitors.

PMID- 8870885
TI  - New York State physicians look unfavorably on expanded role for community
      pharmacists.

PMID- 8870886
TI  - ASHP's new National Clinical Skills Competition for students.

PMID- 8870887
TI  - Adverse drug reaction monitoring in the HMO setting.

PMID- 8870888
TI  - Evaluating baseline prescribing practices.

PMID- 8870889
TI  - Keeping patient information confidential.

PMID- 8870890
TI  - Customer-service call centers.

PMID- 8870892
TI  - Benchmark analysis of strategies hospitals use to control antimicrobial
      expenditures.
AB  - Hospital expenditures on antimicrobial drugs, antimicrobial management practices,
      and the effects of these practices were studied. A survey on institutional
      budget, size, and staffing; intensive care unit drug costs and use evaluations;
      and pharmacy expenditures, including antimicrobial costs, for 1993 and 1994 was
      sent to 122 hospitals. The written survey was followed by telephoned questions
      regarding each institution's antimicrobial management and expenditures, and any
      perceived link between the two. Hospitals were grouped by size and type, data
      were normalized to costs per occupied bed and costs per occupied bed per case mix
      index, and averages for each size category were calculated for general
      institutional information and expenses per antimicrobial. Eighty-eight
      institutions (72%) responded. Although 61% to 74% of the respondents used an
      antimicrobial formulary to restrict drug choices and control costs, average total
      antimicrobial expenses increased by more than $300 per occupied bed between 1993
      and 1994. Only 7% of the institutions saw decreased costs of $500 or more per
      occupied bed. The most common reasons for these decreases were restructuring of
      pricing contracts and implementation of educational programs. The replacement of
      one formulary alternative with another led to increases in the use of
      antimicrobials other than the replacement drug and often did not produce savings.
      The replacement of one formulary antimicrobial with another led more to
      costshifting than to overall savings.

PMID- 8870891
TI  - Quinupristin-dalfopristin (RP 59500): an injectable streptogramin combination.
AB  - The pharmacology, pharmacokinetics, activity, and potential clinical role of
      quinupristin-dalfopristin (RP 59500) are described. Quinupristin-dalfopristin is
      the first injectable formulation of the streptogramin antibiotics. Streptogramin
      drug products are each composed of two chemically distinct compounds, which when
      administered together act synergistically by inhibiting bacterial protein
      synthesis. Quinupristin-dalfopristin has shown activity in vitro against many
      strains of streptococci and staphylococci, including methicillin- and
      erythromycin-resistant strains of staphylococci. The combination is more active
      against Enterococcus faecium than Enterococcus faecalis. It has also shown
      activity in vitro against certain gram-negative organisms and anaerobes. The mean
      maximum blood concentration at the end of a one-hour infusion ranged from 0.95
      mg/L for a 1.4-mg/kg dose to 24.2 mg/L for a 29.4-mg/kg dose; there was a linear
      correlation between dose and mean area under the concentration-time curve. Mean
      half-life ranged from 1.27 to 1.53 hours. The drug is under investigation in the
      United States in Phase III trials. Of 60 evaluable patients with documented
      bacteremia involving E. faecium resistant to vancomycin, 40 (67%) had a favorable
      clinical response. Of 11 patients with bacteremia caused by methicillin-resistant
      Staphylococcus aureus, 78% had a favorable response. The efficacy of quinupristin
      dalfopristin in treating resistant infections has also been suggested by smaller
      studies and case reports. The drug may be useful in the prophylaxis of
      endocarditis. Adverse reactions are generally mild and transient. Quinupristin
      dalfopristin may be useful in treating serious gram-positive infections, but more
      clinical study is needed.

PMID- 8870893
TI  - Pharmacy-based skin-testing program in a community hospital.
AB  - The establishment of a pharmacy-based skin-testing program at a community
      hospital is described. Problems with existing skin testing were brought to the
      attention of the pharmacy and therapeutics committee, which decided that one
      group of caregivers within the hospital should be chosen and trained to perform
      skin testing. A problem-solving team identified specific problems and developed
      solutions. The top four causes of the skin-testing problems were failure to
      follow procedure, inaccurate reading of tests, failure to report positive
      results, and failure to document results. Groups within the hospital who might
      perform skin testing were assessed according to several criteria; the pharmacy
      staff was selected because of ease of notification, availability, and ability to
      conduct follow-through (reading, documenting, and reporting results). Other
      improvements were step-by-step instructions for all phases of skin testing, a
      portable skin-test supply kit, and a skin-test record form to be placed in the
      physician progress notes. Pharmacists were trained by the employee health nurse.
      Pharmacist skin testing began in March 1995. Pharmacists administered tests to 93
      inpatients and about 250 employees during the first 13 months of the program, and
      no problems were reported. Establishment of a pharmacy-based skin-testing program
      improved the quality of inpatient skin testing and enabled pharmacists to
      increase their role in patient care.

PMID- 8870894
TI  - Anabolic steroid use among adolescents in Nebraska schools.
AB  - The extent of anabolic steroid use among adolescent sports participants and
      nonparticipants in Nebraska schools was studied. The Nebraska Secondary School
      Survey administered in 1991 contained 19 new items designed to determine rates of
      use of anabolic steroids and to measure participation in school sports. Schools
      participating in the survey are part of the Toward a Drug Free Nebraska training
      project; when the 1991 survey was conducted, training did not address ergogenic
      drug use. The survey was administered on a voluntary and confidential basis to
      Nebraska students in grades 7 through 12. A total of 4722 students in 62
      secondary schools were surveyed; 3183 (67.4%) identified themselves as
      participants in school-sponsored sports. Of all the respondents, 117 (2.5%)
      reported having used anabolic steroids in the preceding 30 days. Some 4.5% of all
      the male respondents were steroid users, versus 0.8% of all the females. Of the
      students who reported using anabolic steroids, 72.6% were sports participants.
      Steroid users, whether they participated in sports or not, were more likely to
      use alcohol, tobacco, and other drugs than were nonusers of steroids. Among
      sports participants and nonparticipants, anabolic steroid users were more likely
      than nonusers to report acting violently. Nebraska students (grades 7 through 12)
      who participated in school-sponsored sports were more likely than non
      participants to use anabolic steroids. Steroid-using athletes were more likely to
      use alcohol, tobacco, and other drugs than athletes who did not use steroids.

PMID- 8870895
TI  - Stability of ketoconazole, metolazone, metronidazole, procainamide hydrochloride,
      and spironolactone in extemporaneously compounded oral liquids.
AB  - The stability of drugs commonly prescribed for use in oral liquid dosage forms
      but not commercially available as such was studied. Ketoconazole 20 mg/mL,
      metolazone 1 mg/mL, metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL,
      and spironolactone 25 mg/mL were prepared in a 1:1 mixture of Ora-Sweet and Ora
      Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock
      Laboratories), and cherry syrup and placed in 120-mL polyethylene terephthalate
      bottles. The sources of the drugs were powder, capsules, and tablets. Six bottles
      were prepared per liquid; three were stored at 5 degrees C and three at 25
      degrees C, all in the dark. A sample was removed from each bottle immediately
      after preparation and at intervals up to 60 days and analyzed for drug
      concentration by stability-indicating high-performance liquid chromatography. At
      least 93% of the initial drug concentration was retained in all the oral liquids
      for up to 60 days. There were no substantial changes in the appearance or odor of
      the liquids, or in the pH. Ketoconazole 20 mg/mL, metolazone 1 mg/mL,
      metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL, and spironolactone
      25 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three
      extemporaneously compounded oral liquids. INDEX TERMS: Anti-infective agents;
      Antifungals; Capsules; Cardiac drugs; Cherry syrup; Compounding; Containers;
      Diuretics; Incompatibilities; Ketoconazole; Liquids; Metolazone; Metronidazole;
      Polyethylene terephthalate; Powders; Procainamide hydrochloride; Spironolactone;
      Stability; Storage; Suspending agents; Tablets; Temperature; Vehicles.

PMID- 8870896
TI  - Serum triglyceride levels in patients treated with clozapine.

PMID- 8870898
TI  - Internal reform at the FDA.

PMID- 8870897
TI  - Legislative reform proposals.

PMID- 8870899
TI  - ASHP response to FDA reform.

PMID- 8870900
TI  - Antimicrobial formulary control: is the glass half empty or half full?

PMID- 8870901
TI  - Barriers to disease management.

PMID- 8870902
TI  - Impact of dosage-monitoring system on frequency of seizures associated with
      imipenem-cilastatin.

PMID- 8870903
TI  - Minimizing the occurrence of red-man syndrome.

PMID- 8870904
TI  - Accuracy of filled elastomeric infusion device after long-term storage.

PMID- 8870905
TI  - Tuberculosis: old nemesis, new problems.

PMID- 8870906
TI  - Status of tuberculosis infection control programs at United States hospitals,
      1989 to 1992. APIC. Association for Professionals in Infection Control and
      Epidemiology.
AB  - BACKGROUND: Recent nosocomial outbreaks have raised concern about the risk of
      Mycobacterium tuberculosis transmission in United States hospitals. METHODS: To
      determine current tuberculosis (TB) infection control practices, we surveyed a
      sample of approximately 3000 acute care facilities about the number of patients
      with drug-susceptible or multidrug-resistant TB (MDR-TB), health care worker
      (HCW) tuberculin skin test (TST) results, and compliance with the 1990 Centers
      for Disease Control and Prevention (CDC) TB guidelines. Analyses were restricted
      to one response per hospital. RESULTS: Personnel at 1494 (49.8%) hospitals
      returned a completed survey. Respondent hospitals had a mean of 881 HCWs (range 8
      to 10,000) and 196 (range 6 to 2450) beds; 62% percent were community nonteaching
      hospitals. Of respondent hospitals providing data for 1989 through 1992, the
      proportion that cared for patients with TB or MDR-TB increased from 46.4% to
      56.6% and 0.8% to 4.5%, respectively. The pooled mean HCW TST positivity rate at
      hire rose from 0.95% to 1.14%, and the pooled mean HCW TST conversion rate
      increased from 0.40% to 0.51%. In 1992, when we compared hospitals with zero, one
      to five, or six or greater patients with TB, the risk of a positive HCW TST
      result at hire or at routine testing significantly increased with increasing
      number of patients with TB. From 1989 through 1992, the number of hospitals
      reporting the use of surgical masks for HCW respiratory protection decreased from
      96.8% to 66.8%. In 1992, 66% of the hospitals reported compliance with four or
      more of the AFB isolation room criteria specified in the 1990 CDC TB guidelines.
      CONCLUSIONS: Contrary to prior surveys, this study shows that many U.S. community
      hospitals admit patients with TB less frequently than do teaching hospitals, and
      infrequently admit patients with MDR-TB. Because the risk of HCW TST conversion
      varies with hospital characteristics, these data show the importance of
      performing a risk assessment, as recommended in the CDC TB guidelines, for each
      ward and hospital so that TB control measures can be individualized.

PMID- 8870907
TI  - A survey of tuberculosis control programs in seventeen Minnesota hospitals:
      implications for policy development.
AB  - BACKGROUND: Generation of proposed policies directed at interrupting the
      transmission of Mycobacterium tuberculosis resulted in a need for data
      establishing health care worker (HCW) tuberculosis (TB) transmission risk and
      control programs that were in place before 1992. METHODS: A voluntary sample of
      18 Minnesota health care facilities was surveyed retrospectively for the years
      1989 to 1991. The survey was designed to establish the frequency of positive
      tuberculin skin test (TST) results, the rate of positive results during routine
      screening, the incidence of positive TST results identified through exposure
      follow-up, the type of respiratory protection (mask) used, and ventilation
      patterns of TB isolation rooms. The TST testing program, including name of
      product used, method of application, and reading/documentation behaviors, was
      requested. RESULTS: Data were analyzed from 17 hospitals (one long-term facility
      was deleted). Three hospitals screened all HCWs annually; the remaining hospitals
      screened HCWs at varying intervals. Forty-eight positive TST results were
      identified in routine screening. The rate per 10,000 HCWs screened was 5.8 in
      1989; 15.9 in 1990; and 14.8 in 1991. An upward trend was noted in positive TST
      results only in metropolitan teaching/public hospitals. Intercomparisons of TST
      screening data demonstrated that employees located in Greater Minnesota were more
      likely to have positive TST results than employees at facilities in the
      metropolitan area. Hospitals in Greater Minnesota were more likely than
      metropolitan area hospitals to use tuberculin skin test material. HCWs screened
      with tuberculin purified protein derivative were more likely to have positive
      test results than HCWs screened with tuberculin purified protein derivative.
      Unisolated patients with communicable TB accounted for 445 patient days of
      probable risk of exposure for HCWs, without demonstration of a trend by calendar
      year. There were a total of 33 exposure events. Ten of 1031 HCWs screened after
      an exposure event were declared to be TST positive, for an overall conversion
      rate of 9.7 per 1000 employees screened. All hospitals used surgical masks for
      respiratory protection. Seventy-six percent of the hospitals had isolation rooms
      with negative ventilation; 12% reported isolation rooms with neutral pressure.
      CONCLUSION: The practice in Minnesota hospitals surveyed was reasonably
      consistent with the critical elements defined in the 1990 CDC guidelines for an
      effective TB control program. The rate of positive TST results was low, with
      programs in place before 1992. Unified TST programs permitting evaluation of
      programs are endorsed. Respiratory protection should be protective, not
      excessive. Engineering controls of isolation rooms should be ensured. Policy
      development should be driven by the prevalence and incidence of disease in the
      HCW's place of employment.

PMID- 8870908
TI  - Tuberculosis in physicians: compliance with surveillance and treatment.
AB  - BACKGROUND: Physicians have historically shown poor compliance with tuberculosis
      (TB) skin testing and treatment after infection. Studies showed that nearly one
      half of physicians had positive skin test results, but one half to two thirds of
      physicians with negative tuberculin skin test results did not undergo annual skin
      testing despite significant exposure to patients with TB. Compliance with
      chemoprophylaxis after skin test conversion was worse; only 8% to 10% of
      physicians with a positive tuberculin skin test result received antituberculous
      therapy. The Centers for Disease Control and Prevention published guidelines on
      prevention of tuberculosis transmission recommending that all health care workers
      (including physicians) comply with regular skin testing and get appropriate
      follow-up care. The Occupational Safety and Health Administration has adopted the
      guidelines as part of its strategy to prevent occupationally acquired TB. OSHA's
      requirement provided the opportunity to study the effect on physicians of
      hospital-wide attempts to apply those guidelines. No previous study has looked at
      the differences in compliance between physicians in training, full-time staff
      physicians, and part-time staff (associate physicians). Understanding these
      differences will enable the hospital's administration to target efforts to
      improve compliance with TB surveillance and medical therapy after skin test
      conversion. METHODS: Two hundred eighty-four physicians (189 staff physicians, 65
      resident physicians, and 30 associate physicians) responded to a questionnaire
      that asked about demographic and professional characteristics, current status of
      tuberculin skin test results, and follow-up of physicians with positive skin test
      results. RESULTS: We found that 71% of resident and full-time physicians were
      current in their tuberculin skin test status, whereas 66% of associate physicians
      were up to date. Thirteen percent of the resident and full-time physicians had
      positive TB skin test results, compared with 20% of associate physicians. Female
      physicians had a lower prevalence of positive skin test results than did male
      physicians. The departments of pathology, surgery, and pediatrics had the highest
      prevalence of positive test results, followed by radiology, emergency medicine,
      and obstetrics and gynecology. Family practice and internal medicine were among
      the departments with the lowest prevalence of positive skin test results.
      Physicians obtained their skin tests from multiple sources and had their test
      results interpreted in multiple facilities; hence, the test procedure was not
      uniform. Compliance with disease prophylaxis was 55% among the resident
      physicians with positive Mantoux test results, 44% among the full-time staff
      physicians, and only 17% among the associate physicians. More than half of the
      physicians with positive Mantoux test results remained untreated. CONCLUSION:
      Physicians have unique issues in complying with TB surveillance that need to be
      specifically addressed by hospitals in light of guidelines enforceable by the
      Occupational Safety and Health Administration. Resident physicians were the most
      compliant with TB surveillance and treatment after infection. Staff and associate
      staff physicians had poor compliance with treatment. Although this study shows
      some improvement when compared with prior studies on physician compliance,
      hospital follow-up and enforcement may be necessary to bring about significant
      behavioral change among physicians.

PMID- 8870909
TI  - Challenges associated with assessment of risk for tuberculosis in a dental school
      setting.
AB  - BACKGROUND: Reported risk among health care workers, related to tuberculosis
      exposure, motivated us to accurately assess this occupational risk at our College
      of Dentistry. METHODS: Our sample population included all dental students
      entering their junior (third) year (beginning of maximum patient exposure).
      Screening for tuberculosis infection, with the standardized Mantoux test
      (purified protein derivative [PPD]), was conducted by the authors; several
      variables, previously associated with inaccurate test results in the literature,
      were controlled for during the study. RESULTS: Among the study population of 158
      students, the PPD conversion rate, as determined by one-step testing, after one
      academic year was 10.6%. To further investigate factors (other than possible
      workplace exposure) contributing to PPD conversion in the study population, the
      authors also examined PPD results from previous employee and student screenings
      and conducted a retrospective chart review of selected patients registered at the
      college for the same period. CONCLUSIONS: We found that being born outside of the
      United States and having previously received bacille Calmette-Guerin vaccine are
      associated with positive PPD test results. In addition, PPD conversion among the
      study group may not be associated with occupational exposure at the College but,
      in fact, may be related to other factors, including community- and hospital-based
      clinical exposure. Finally, we recommend further research that examines the
      possible systemic effects of periodic testing with PPD on test subjects.

PMID- 8870910
TI  - Guideline for prevention of intravascular device-related infections. Part I.
      Intravascular device-related infections: an overview. The Hospital Infection
      Control Practices Advisory Committee.

PMID- 8870911
TI  - Guideline for prevention of intravascular device-related infections. Part II.
      Recommendations for the prevention of nosocomial intravascular device-related
      infections. Hospital Infection Control Practices Advisory Committee.

PMID- 8870912
TI  - Pulmonary tuberculosis in a homeless person.
AB  - Tuberculosis disproportionately affects certain segments of society, such as the
      homeless, and can cause extremely serious disease among persons with severely
      impaired cellular immunity, especially those with HIV infection. Inhalation of
      droplet nuclei, which are the airborne residual of droplets expelled from an
      infected host, is the primary means of transmission. Factors associated with
      transmission in shelters for the homeless include crowding, inadequate
      ventilation, and poor compliance with drug therapy. One of the greatest
      challenges to treatment of this infection among the homeless is the provision of
      adequate follow-up of patients who have begun therapy. Many individuals do not
      complete their treatment regimen. This creates an environment in which the
      transmission of tuberculosis, including multi-drug-resistant strains, can occur.
      Prevention strategies should focus on rapid identification and treatment of
      persons with active disease and latent tuberculosis infections. Ventilation with
      good exchange of fresh air or the addition of air cleaning devices may aid in
      reducing risks of transmission of disease.

PMID- 8870913
TI  - Self-paced learning stations for tuberculosis respirator training: report of a
      pilot program.
AB  - BACKGROUND: In response to the Centers for Disease Control and Prevention's
      recently issued "Guidelines for Preventing the Transmission of Mycobacterium
      Tuberculosis in Health-Care Facilities, 1994," during May 1994 we implemented and
      evaluated a pilot tuberculosis respirator training program that used four self
      directed learning stations, through which participants proceeded at their own
      pace. Employee tuberculin skin testing was included in the training program.
      METHODS: The time required to train each employee was recorded. At the completion
      of the training program, all participants were asked to assess their ability to
      attain the learning objectives and whether they believed the program format was
      an effective and efficient use of their time. Two weeks later, a convenience
      sample of 100 employees completed an 11-question test designed to measure
      knowledge retention. RESULTS: One hundred seventy-six employees completed
      training during the pilot period. The average time necessary to train each
      employee was 19.5 minutes. Overall 97.1% of participants stated that they were
      able to fully meet the course objectives. Test scores among the convenience
      sample averaged 88% 2 weeks after training. CONCLUSIONS: The use of self-paced
      stations for tuberculosis respirator training and employee tuberculosis skin test
      screening was both effective and time-efficient for employees. We have expanded
      this program to include all of our approximately 500 employees who may be exposed
      to tuberculosis.

PMID- 8870914
TI  - Advantages and limitations of automatic flexible endoscope reprocessors.
AB  - The advantages and limitations of automatic flexible endoscope reprocessors
      (AFERs) are presented. These medical devices can increase patient safety and
      minimize personnel exposure to the liquid chemical germicide and its vapors. Some
      models feature a printer to document important reprocessing parameters, an in
      line tap water filtration system to reduce the likelihood of endoscope (and
      patient) contamination, and a heater to satisfy the elevated temperature
      requirements of some liquid chemical germicide labels. Although they offer
      significant advantages compared with manual reprocessing, AFERs have their
      limitations. Current models do not automate every endoscope reprocessing step and
      are not typically designed to reprocess every endoscope channel. Some AFER models
      may have to be periodically decontaminated to ensure that their internal
      components do not support microbial colonization. Moreover, their cost per cycle
      can be considerably more than manual reprocessing without necessarily reducing
      overall reprocessing time. Its limitations notwithstanding, an AFER is likely to
      be an asset in a busy endoscopy center. In addition to comparing automated and
      manual reprocessing, this article addresses important reprocessing issues and
      purchasing concerns.

PMID- 8870915
TI  - A review of the plasma sterilization systems.

PMID- 8870916
TI  - APIC guideline for selection and use of disinfectants. 1994, 1995, and 1996 APIC
      Guidelines Committee. Association for Professionals in Infection Control and
      Epidemiology, Inc.

PMID- 8870917
TI  - Biochemical and molecular analysis in a patient with the severe form of Hunter
      syndrome after bone marrow transplantation.
AB  - Hunter syndrome (mucopolysaccharidosis type II, or MPS II) results from a
      deficiency of iduronate-2-sulfatase (IDS) activity due to a primary genetic
      defect in the X-chromosomal iduronate-2-sulfatase gene. We have studied a 10-year
      old male, diagnosed with Hunter syndrome at age 2 years, who underwent bone
      marrow transplantation (BMT) at age 5 years. To evaluate the metabolic effect of
      BMT, biochemical and enzymatic studies were performed. Urinary glycosaminoglycans
      (GAGs) were quantitated, and iduronate-2-sulfatase activity was measured in
      serum, leukocytes, and liver homogenates. Decreased urinary glycosaminoglycan
      excretion and increased iduronate-2-sulfatase activity in serum and leukocytes
      were observed. Furthermore, molecular analysis was performed using reverse
      transcriptional polymerase chain reaction (RT-PCR) sequencing and restriction
      enzyme assay. The patient was found to have a novel nonsense mutation, L279X (TTA
      to TGA) in exon 6 of the IDS gene, inherited from his mother. A comparison of the
      DNA contents of cultured skin fibroblasts prior to BMT with leukocyte DNA after
      BMT showed coexisting host mutant and donor normal alleles in post-BMT leukocyte
      DNA. We postulate that the L279X mutation is a severe disease-causing mutation
      for Hunter syndrome.

PMID- 8870918
TI  - Variants of chromosome 9 with additional euchromatic bands: two case reports.
AB  - This paper documents a prenatal case of maternally inherited subtle duplication
      of chromosome 9 bands q21.1 to q21.2 and a second case with two G-bands within
      the 9qh region. Cytogenetic studies of these cases included G-banding, C-banding,
      fluorescent in situ hybridization (FISH) using chromosome 9 specific library
      probe, and the classical satellite probe. In both patients, the additional bands
      were G-bands and C-band negative. By FISH studies they were negative for the
      satellite heterochromatin probe and positive for the chromosome 9 painting probe.
      Therefore, the extra bands were presumably euchromatin and part of chromosome 9.
      The chromosome 9 variants and their possible mechanisms of origin are discussed.

PMID- 8870919
TI  - Toward quality assurance for metaphase FISH: a multi-center experience.
AB  - Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of
      clinical cytogenetics, no organization sponsors multi-center determinations of
      the efficacy of probes. We report on 23 laboratories that volunteered to provide
      slides and to use a probe for SNRPN and a control locus. Experiences with FISH
      for these laboratories during 1994 ranged from 0 to 645 utilizations (median =
      84) involving blood, amniotic fluid and bone marrow. In an initial study of
      hybridization efficiency, the median percentage of metaphases from normal
      individuals showing two SNRPN and 2 control signals for slides prepared at each
      site was 97.0 (range = 74-100); for slides prepared by a central laboratory, it
      was 97.8 (range = 81.6-100). In a subsequent blind study, each laboratory
      attempted to score 5 metaphases from each of 23 specimens [8 with del(15) (q11.2-
      >q12) and 15 with normal 15 chromosomes]. Of 529 challenges, the correct SNRPN
      pattern was found in 5 of 5 metaphases in 457 (86%) and in 4 of 5 in 33 (6%).
      Ambiguous, incomplete or no results were reported for 32 (6%) challenges. Seven
      (1%) diagnostic errors were made including 6 false positives and 1 false
      negative: 1 laboratory made 3 errors, 1 made 2, and 2 made 1 each. Most errors
      and inconsistencies seemed due to inexperience with FISH. The working time to
      process and analyze slides singly averaged 49.5 minutes; slides processed in
      batches of 4 and analyzed singly required 36.9 minutes. We conclude that
      proficiency testing for FISH using an extensive array of challenges is possible
      and that multiple centers can collaborate to test probes and to evaluate costs.

PMID- 8870920
TI  - Juvenile rheumatoid arthritis in velo-cardio-facial syndrome: coincidence or
      unusual complication?
AB  - We report on two patients with velo-cardio-facial syndrome (VCFS) and juvenile
      rheumatoid arthritis (JRA). The first, a 9-year-old girl, presented with
      microcephaly, characteristic face, congenital heart disease, and velopharyngeal
      insufficiency. Fluorescence in situ hybridization (FISH) study showed deletion of
      D22S75 (N25), confirming the diagnosis of VCFS. At age 7, she developed joint
      pain, and polyarticular JRA was diagnosed. Awareness of this case led to the
      subsequent diagnosis of VCFS (also confirmed by FISH) in another, unrelated 12
      year-old girl with characteristic face, hypernasal speech, and obesity. JRA was
      first diagnosed in this case at age 5 years, and she subsequently developed
      severe polyarticular disease. Neither patient had clinical or laboratory evidence
      of immunodeficiency. This observation represents the first report of the
      association of JRA with VCFS and raises the question of whether this is a
      coincidental association or a rare complication of this condition.

PMID- 8870921
TI  - Proximal trisomy 1q in a girl with developmental delay and minor anomalies.
AB  - We report on a girl with developmental delay, macrocephaly, facial asymmetry,
      small downturned palpebral fissures, high and narrow palate, micrognathia, short
      neck, a heart defect, and unilateral renal agenesis. Cytogenetic analysis showed
      a proximal tandem duplication of the long arm of chromosome one (1q12-->q21.3).
      This abnormality was suggested by G- and C-banding but it was specifically
      characterized by fluorescent in situ hybridization (FISH). Clinical findings in
      our patient are compared with those of the literature in an attempt to delineate
      the phenotype in patients with proximal 1q duplication.

PMID- 8870922
TI  - A new observation of two cases of acrofacial dysostosis type Genee-Wiedemann in a
      family--remarks on the mode of inheritance: report on two sibs.
AB  - We report on a Yugoslavian sibpair with postaxial acrofacial dysostosis type
      Genee-Wiedemann with some novel signs which broaden the spectrum of this
      syndrome. The manifestations of the present cases are compared with those of the
      previously described patients. Life expectancy, change of symptoms over time, and
      the mode of inheritance are discussed.

PMID- 8870923
TI  - Phenotypic variability in monozygotic twins with neurofibromatosis 2.
AB  - Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome
      22q12 cause a clinically variable autosomal dominant syndrome characterized by
      bilateral vestibular schwannomas (VSs), other nervous system tumors, and early
      onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with
      NF2, all with bilateral VSs, to separate genetic from nongenetic causes of
      clinical variability. The evaluation included gadolinium-enhanced high-resolution
      magnetic resonance imaging of the head and spine, neuro-ophthalmic examination
      with slit lamp, physical examination, and zygosity testing with microsatellite
      markers. Each MZ pair was concordant for general phenotypic subtype (mild or
      severe) and often for the affected organ systems. However, the MZ pairs were
      discordant for some features of disease presentation or progression. For example,
      all three pairs were discordant for presence or type of associated cranial
      tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at
      least partly due to stochastic processes, such as the loss of the second NF2
      allele or alleles of other genes.

PMID- 8870924
TI  - Variant of Coffin-Siris syndrome or previously undescribed syndrome?
AB  - We describe a 23-year-old woman with growth and mental retardation, hypoplasia of
      the nails and distal phalanges, particularly of the fifth fingers and toes,
      hirsutism, and a "coarse" face with large mouth and large tongue, and bushy
      eyebrows. Follow-up from birth to adulthood showed that developmental delay and
      hypoplasia of nails and distal phalanges are permanent signs. Sparse scalp hair,
      hypotonia, and feeding difficulties were present in early infancy. Later, growth
      retardation, hirsutism, and a "coarse" face with midface hypoplasia, broad nose,
      and large mouth became more impressive. Differential diagnosis includes a number
      of conditions, particularly Coffin-Siris syndrome, which is the most likely but
      not completely convincing diagnosis. Therefore, this woman might represent a
      variant of Coffin-Siris syndrome or a new entity.

PMID- 8870925
TI  - Isochromosome Xq in Klinefelter syndrome: report of 7 new cases.
AB  - In this collaborative study we report on 2 prenatally and 5 postnatally diagnosed
      cases with a 47,X,i(Xq),Y chromosomal constitution. Excepting tall stature, the 5
      adult patients showed all typical manifestations of Klinefelter syndrome. Taken
      together with previously reported cases, these data suggest that Klinefelter
      syndrome with isochromosome Xq has a favorable prognosis with normal mental
      development, and with normal-to-short stature. The prevalence of this Klinefelter
      variant is calculated to be between 0.3-0.9% in males with X chromosome
      polysomies.

PMID- 8870926
TI  - Mental retardation in a boy with an interstitial deletion at Xp22.3 involving
      STS, KAL1, and OA1: implication for the MRX locus.
AB  - Although genotype-phenotype correlations in male patients with various types of
      nullisomy for Xp22.3 have assigned a locus for X-linked mental retardation (MRX)
      to an approximately 3-Mb region between DXS31 and STS, the precise location has
      not been determined. In this paper, we describe a 14 7/12 year old Japanese boy
      with mental retardation and an interstitial deletion at Xp22.3 involving STS,
      KAL1, and OA1, and compare the deletion map with that of previously reported
      three familial male patients with low-normal intelligence and a similar
      interstitial deletion at Xp22.3. The results suggest that the MRX gene is further
      localized to the roughly 1.5-Mb region between DXS1060 and DXS1139.

PMID- 8870927
TI  - Lymphoproliferative disorders in Sotos syndrome: observation of two cases.
AB  - Sotos syndrome is included among the overgrowth disorders, most of which have an
      increased risk of neoplasms. Sotos syndrome does not appear to be related to a
      specific tumor type, but rather to the development of solid tumors of ectodermal
      or mesodermal origin in general. We report on two Sotos syndrome patients who
      developed a non-Hodgkin lymphoma and an acute lymphoblastic leukaemia,
      respectively. Our experience suggests that there may exist a high frequency of
      lymphoproliferative disorders in Sotos syndrome, and points out the importance of
      a long-term follow-up of Sotos syndrome patients, to detect a possible neoplastic
      evolution.

PMID- 8870928
TI  - Friedreich ataxia in Acadian families from eastern Canada: clinical diversity
      with conserved haplotypes.
AB  - The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodegenerative
      disease, remains elusive. The current candidate region of about 150 kb lies
      between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1.
      Linkage homogeneity between classical FRDA and a milder, slowly progressive
      Acadian variant (FRDA-Acad) has been demonstrated. An extended D9S15-D9S5
      haplotype (C6) predominates in FRDA-Acad chromosomes from Louisiana. We studied
      10 Acadian families from New Brunswick, Canada. In eight families, affected
      individuals conformed to the clinical description of FRDA-Acad; in one, 2 sibs
      presented with spastic ataxia (SPA-Acad). In the last family, 2 sibs had FRDA
      Acad, and one had SPA-Acad. We found that SPA-Acad is linked to the FRDA gene
      region. The C6 haplotype and a second major haplotype (B7) were identified. The
      same ataxia-linked haplotypes segregated with both FRDA-Acad and SPA-Acad in two
      unrelated families. The parental origins of these haplotypes were different. Our
      observation of different phenotypes associated with the same combination of
      haplotypes may point to the influence of the parent of origin on gene expression,
      indicate the effect of modifier genes, or reflect the presence of different
      mutations on the same haplotypes. Our findings underline the need to investigate
      families with autosomal-recessive ataxias for linkage to the FRDA region, despite
      lack of key diagnostic manifestations such as cardiomyopathy or absent deep
      tendon reflexes.

PMID- 8870929
TI  - Olfactory loss in Usher syndrome: another sensory deficit?

PMID- 8870930
TI  - Velo-facio-skeletal syndrome versus Aarskog syndrome.

PMID- 8870931
TI  - Web-neck anomaly and its association with congenital heart disease.

PMID- 8870932
TI  - Deep neck infections.

PMID- 8870933
TI  - Papillary carcinoma associated with black thyroid gland.

PMID- 8870934
TI  - Exostoses of the external auditory canal in Oregon surfers.
AB  - PURPOSE: The objectives of this study were to determine the cold water exposure
      necessary to produce exostoses of the external auditory canal in individuals who
      predominantly surf along the Oregon and/or the northern California coastline and
      to ascertain from surfers' otologic histories symptoms attributable to exostoses.
      MATERIALS AND METHODS: Free ear examinations were provided at two surf shops in
      northern Oregon. The ear canals were examined with an otoscope, and each surfer
      was given a summary score indicating the percentage of both canals that was
      obstructed by exostoses. Surfers were then categorized according to the number of
      years surfing and the number of sessions surfing per year. RESULTS: Twenty-one
      surfers met our criteria for analysis. The degree of ear canal obstruction
      significantly increased with increasing number of years surfing (P < .001) and
      with increasing number of sessions surfing per year (P < .01). The median summary
      scores were 7.5, 63.0, and 93.0 for individuals who respectively surfed between 1
      and 5 years, between 6 and 15 years, and greater than 15 years. The median
      summary scores were 10.0 for individuals who surfed 50 sessions or less per year
      versus 87.5 for individuals who surfed greater than 50 sessions per year. Most
      surfers with exostoses had minimal complaints. Only one patient had a history of
      surgical treatment. CONCLUSION: Individuals who surf 5 years or less are unlikely
      to develop exostoses unless they are surfing greater than 50 sessions per year.
      Exostoses are typically a benign malady that do not require surgical therapy.

PMID- 8870935
TI  - Mortality and morbidity with intraoperative radiotherapy for head and neck
      cancer.
AB  - OBJECTIVE: To critically evaluate the morbidity and mortality associated with
      intraoperative radiation therapy (IORT). IORT allows the delivery of large single
      doses of radiation to a visible tumor bed with exclusion (or shielding) of
      critical normal structures from the treatment field. Morbidity and mortality
      associated with IORT has been directly studied in abdominal malignancies, but
      only briefly mentioned in the head and neck literature. PATIENTS AND METHODS: At
      the Arthur G. James Cancer Hospital, The Ohio State University Medical Center, 53
      patients with advanced head and neck cancer were treated with surgical resection
      and IORT. Twenty of these patients had intraoperative high-dose-rate (HDR)
      brachytherapy, whereas the remaining 33 received intraoperative electron beam
      therapy. All patients received 7.5 to 20 Gy of radiation. Those treated were
      reviewed evaluating perioperative mortality, major and minor complications, and
      length of hospital stay. All patients have been followed at least 3 months
      postoperatively. RESULTS: There were no perioperative deaths. Additionally, there
      was no increase in the number of complications or length of hospital stay
      associated with the use of IORT. The mean length of hospital stay was 13.0 days.
      The major complication rate was 16.8%. Of the major complications, 9% were
      medical and not related to the surgical site. The minor complication rate was 8%.
      CONCLUSION: As we strive to increase control of advanced head and neck cancer,
      IORT may play an exciting role for intensifying the therapy. At this institution,
      IORT did not add to the mortality or morbidity of an aggressive multimodality
      treatment schema.

PMID- 8870936
TI  - Outgrowing schwannomas arising from tympanic segments of the facial nerve.
AB  - PURPOSE: Although there have been numerous reports of clinical cases of facial
      nerve schwannoma, histopathologic studies of its early stages of development are
      rare. The purpose of this study was to describe the incidence, origin, and
      pathology of small, asymptomatic schwannomas of the facial nerve. MATERIALS AND
      METHODS: Fifteen hundred twenty-six ears from the human temporal bone collection
      of the Otitis Media Research Center Otopathology Laboratory at the University of
      Minnesota were studied under light microscopy. RESULTS: Twelve bones with
      morphologic indications of type A Antoni tissue that mimics facial schwannoma in
      the tympanic cavity were selected. The 12 ears were from nine individuals with
      asymptomatic histories. The twelve schwannomas developed from perineurium at
      dehiscences in the facial canal near the oval window, forming defects in the
      epineurium by growth of Schwann cells downward and outward toward the stapes. No
      obvious compressions or lesions within fibers in the facial nerve were observed.
      CONCLUSION: Because these tumors grow slowly without hearing loss or facial nerve
      symptoms, they may be mistaken for granulation tissue during surgery for chronic
      otitis media.

PMID- 8870937
TI  - Supraglottic laryngectomy with postoperative radiation versus primary radiation
      in the management of supraglottic laryngeal cancer.
AB  - PURPOSE: The purpose of this review was to study the results of horizontal
      partial laryngectomy (HPL) for supraglottic laryngeal cancer (stages N0 and N+)
      and the effects and morbidity of postoperative radiation therapy (RT), especially
      after bilateral neck dissection, as opposed to primary RT. PATIENTS AND METHODS:
      Of a total of 89 patients, 26 were treated by HPL, 44 by primary RT, and 19 by
      total laryngectomy (TL). Of the HPL patients, 19 of 26 had neck dissection, 10
      were bilateral. Twelve of the patients received postoperative RT, and 10 of 12
      procedures were combined with neck dissection. RESULTS: When comparing the
      results of HPL and primary RT, the locoregional control was equivalent for the N0
      patients, but HPL showed better results in locoregional control for the N+
      patients (P < .0024). Postoperative RT with or without bilateral neck dissection
      did not show an increase in postoperative morbidity. CONCLUSION: Therefore, our
      data suggest that there should be no hesitation in giving postoperative RT where
      indicated, after performing HPL plus unilateral or bilateral neck dissection.
      Patients that are stage N0 should receive primary RT.

PMID- 8870938
TI  - Ophthalmic complications of endoscopic ethmoid surgery and their management.
AB  - PURPOSE: The proximity of the paranasal sinuses to the orbit puts the anterior
      visual pathways at risk during sinus surgery. Although the ophthalmic
      complications of sinus surgery are well known to the otolaryngologist, they are
      rarely encountered in clinical practice. Several recommendations will help the
      surgeon performing intranasal sinus surgery. MATERIALS AND METHODS: To study the
      incidence of orbital complications of intranasal ethmoid surgery, a retrospective
      review of 372 cases, most of them bilateral, was performed. RESULTS: Our series
      of 372 patients who underwent endoscopic sinus surgery showed five orbital
      complications. CONCLUSION: several recommendations may help the surgeon to avoid
      any ophthalmic complication. When orbital wall dehiscence is suspected, either by
      CT scan or at surgery, especially in a previously operated case, extreme care
      should be taken not to penetrate the periorbita. If orbital fat protrudes into
      the operative field, it should not be pulled or twisted in an attempt to remove
      it. The surgeon should seek the cooperation of the anesthesiologist working the
      case. A knowledge of the variable anatomy is essential to avoid iatrogenic
      injury. The surgeon should be aware of the different complications for early
      recognition and management.

PMID- 8870939
TI  - A case of primary laryngeal T-cell lymphoma in a patient with acquired
      immunodeficiency syndrome.

PMID- 8870940
TI  - Transitional features of benign and malignant oncocytic tumors: report of two
      cases.

PMID- 8870941
TI  - Craniofacial resection for vascular leiomyoma of the nasal cavity.

PMID- 8870942
TI  - Laryngopyocele: an atypical case.

PMID- 8870943
TI  - Wegener's granulomatosis of the skull base.

PMID- 8870944
TI  - Squamous cell carcinoma in a thyroglossal duct cyst (TGDC): clinical
      presentation, diagnosis, and management.
AB  - Squamous cell carcinoma arising in a TGDC is a rare event, and a high index of
      suspicion is therefore needed for reaching a correct preoperative diagnosis to
      plan adequate therapy. The work-up should include fine needle aspiration cytology
      and high-resolution CT scan. The recommended therapy is adequate wide resection
      with frozen section control of the surgical margins. For localized lesions within
      the TGDC (diagnosed as an incidental histological finding), the Sistrunk
      operation is adequate. If, however, the tumor invades surrounding structures,
      wider resections (which may include strap muscles, thyroid, larynx, or base of
      tongue) are recommended. Neck dissection is reserved for cases with nodal
      metastasis. There is no role for prophylactic neck dissections except perhaps for
      the paratracheal nodes. Postoperative radiation therapy is recommended for larger
      lesions, positive surgical margins, or extensive nodal disease. Strict follow-up
      is recommended for prolonged periods of time, because local recurrences are
      common and could occur many years after the initial treatment.

PMID- 8870945
TI  - Genetic studies in Medzev, an isolate in south-eastern Slovakia. 1. History,
      demography, marriage patterns.
AB  - In Medzev, a village located in South-Eastern Slovakia, the secular variation of
      two indices of genetic isolation has been studied. It could be seen that this
      village was highly isolated till the beginning of the 20th century. Both indices
      show a tendency to increase in the first five decades of this century. For the
      entire period from 1766-1950 the coefficient of inbreeding estimated by the
      method of isonymy was found to be F = 0.0074 with different ratios of random (Fr)
      and non-random (Fn) components in particular periods. The coefficient of
      inbreeding estimated from the ecclesiastical dispensations for marriages comes to
      F = 0.0019. The genetic significance of the changes in the population structure
      of this village will be analyzed in further studies.

PMID- 8870946
TI  - Northrhine Westphalian data on the locus F13B.
AB  - A population study was carried out on 301 ethnic Germans from Dusseldorf
      (Northrhine Westphalia) using the short tandem repeat (STR) system HumF13B
      (Coagulation Factor XIIIB). Five different alleles were detected. No deviations
      from the Hardy-Weinberg equilibrium could be observed. In spite of the
      successfulness of the system only a few population data exist. A pooled sample
      from Northrhine Westphalia has to be used as preliminary database for forensic
      and anthropological purposes.

PMID- 8870947
TI  - A seven year anthropobiological survey on the distribution of abnormal
      hemoglobins in Cameroon.
AB  - Within the frame of an anthropobiological survey on some populations of Cameroon
      (1985-1991), Hb beta data were collected from numerous ethnic groups including
      Bakaka, Bamileke, Daba, Fali, Guiziga, Kanuri, Mada, Mafa, Mundang, Uldeme,
      Podokwo, Tali, Tupuri, Fulbe, Mandara, Ewondo and Bassa. Hb beta *S allele
      frequencies ranged from 0.008 +/- 0.003 (among Fali) to 0.152 +/- 0.020 (among
      Mandara) and 0.152 +/- 0.044 (among Podokwo), whereas Hb beta *S was found to be
      absent among Tupuri. Hb beta *C was observed among Bamileke (0.001 +/- 0.001),
      Fali (0.003 +/- 0.002), Fulbe (0.002 +/- 0.002), Mafa (0.005 +/- 0.005), Mundang
      (0.005 +/- 0.005), Tupuri (0.010 +/- 0.007) and Podokwo (0.015 +/- 0.015). The
      possible reasons for these variations in allele frequencies are discussed.

PMID- 8870948
TI  - Variation in palmar interdigital ridge-counts among the 20 Dhangar castes of
      Maharashtra, India.
AB  - Bilateral palmar prints of 2927 males of 20 endogamous Dhangar castes of
      Maharashtra, India, were studied for the distributions of a-b, b-c and c-d
      interdigital ridge-counts. The ridge-counts have been utilized for examining the
      inter-population affinities among the Dhangar castes. The distribution of a-b
      ridge-counts is symmetrical and normal in Dhangar castes. The distributions of b
      c and c-d ridge-counts on both palms also show (nearly) normal distribution, but
      with a tendency of negative skewness and platykurtosis in c-d ridge-count.
      Equality of means and standard deviations depict significant heterogeneity. The
      decreasing order of magnitude of means of interdigital ridge-counts is a-b > c-d
      > b-c among all the Dhangar castes. Intercaste comparisons reveal a great deal of
      variations in all ridge-counts. The pattern of relationship between the Dhangar
      castes based on the three ridge-counts is in agreement with the expected patterns
      of affinities based on the known ethno-historical evidence. The significant
      finding of the study is that the palmar interdigital ridge-counts follow normal
      distribution and that they are useful in studying inter-population affinities.

PMID- 8870949
TI  - Nutritional status as indicator for reproductive success in !Kung San and Kavango
      females from Namibia.
AB  - The interaction between nutritional status, estimated by using Body mass index,
      and fertility outcome was tested in two female samples from Northern Namibia. It
      turned out, that !Kung San undernourished females had significantly more total
      and surviving offspring than well-nourished and overweight females of these
      population. In contrast within the Kavango group well-nourished females had the
      highest reproductive success. These group specific differences can be interpreted
      as special reproductive strategies to maximize the reproductive success under
      different ecological conditions.

PMID- 8870950
TI  - Mensurational blood has increased HbF.

PMID- 8870951
TI  - Hemoglobin and DNA adduct formation in Fischer-344 rats exposed to 2,4- and 2,6
      toluene diamine.
AB  - Using gas chromatography/mass spectrometry for detection of hemoglobin adducts,
      and 32P-postlabelling for DNA adducts, we examined macromolecular binding in
      Fischer-344 rats administered 2,4-or 2,6-toluene diamine (TDA). The dose-response
      and correlative relationship between the two macromolecules were investigated
      over a range of doses (0-250 mg/kg). The time course of adduct formation and
      removal was also examined. Both TDA isomers induced formation of hemoglobin
      adducts, but only the 2,4-isomer induced DNA binding. Maximum hemoglobin and DNA
      adduct levels were detected 24 h following administration. Both hemoglobin and
      DNA binding increased in a dose-dependent manner. Hemoglobin adduct clearance
      demonstrated a nonlinear decay, with adduct loss occurring faster than normal
      erythrocyte clearance. The effects of metabolic inhibitors on adduct formation
      were examined using piperonyl butoxide and pentachlorophenol to inhibit p450
      isozymes and sulfotransferase, respectively. Microsomal enzymatic activation was
      critical to hemoglobin adduct formation with inhibition by piperonyl butoxide
      reducing adduct yields by over 90%. Sulfation did not appear to play a
      significant role in TDA-induced hemoglobin adduct formation.

PMID- 8870952
TI  - Drug metabolizing enzyme activities in porcine urinary bladder epithelial cell
      cultures (PUBEC).
AB  - Drug metabolizing enzyme activities have been determined in cultured porcine
      urinary bladder epithelial cells (PUBEC) in order to evaluate this system as an
      in vitro model for studies of urinary bladder carcinogens. Activities of several
      phase I and II enzymes were measured in cells cultured for various periods and
      compared with the activities determined in freshly isolated PUBEC. Prostaglandin
      H synthase mediated production of prostaglandin E2 was found both in freshly
      isolated and in cultured PUBEC, whereas cytochrome P450 1A1-associated EROD
      activity was only detectable in freshly isolated bladder cells. The latter
      activity was not inducible by benz(a)anthracene or 3-methylcholanthrene in PUBEC
      cultures. N-acetyltransferase (NAT) activity measured with p-aminobenzoic acid, a
      diagnostic substrate for human NAT-1, was stable and even higher during the
      culture period compared to freshly isolated cells. In contrast, isoniazid (a
      substrate for NAT-2) was not acetylated either in fresh or cultured PUBEC.
      Glutathione S-transferases activity determined with 1-chloro-2,4-dinitrobenzene
      decreased gradually to 50% after 1 week and to 20% after 4 weeks in culture
      compared to fresh cells. A similar decline was also observed for UDP
      glucuronyltransferase activities measured with 1-naphthol. In accordance with the
      reported lack of sulfotransferases in pigs, no sulfation of 1-naphthol or 2
      naphthylamine was detected in PUBEC. Our results show that cultured porcine
      urinary bladder epithelial cells maintain several enzyme activities required for
      the biotransformation of xenobiotics. In future investigations on the mechanism
      of action of bladder carcinogens PUBEC cultures may thus provide a useful in
      vitro model for this target tissue.

PMID- 8870953
TI  - Bone marrow and renal injury associated with haloalkene cysteine conjugates in
      calves.
AB  - Almost 40 years ago, it was reported that cattle-feed which had been extracted
      with hot trichloroethylene and then fed to calves produced renal injury and a
      fatal aplastic anaemia. The toxic factor was subsequently identified as S-(1,2
      dichlorovinyl)-L-cysteine (DCVC). These original findings have been confirmed, a
      single intravenous dose of DCVC at 4 mg/kg, or 0.4 mg/kg intravenously per day
      administered for 10 days to calves produced aplastic anaemia, and renal injury
      after a single dose of 4 mg/kg. The toxicity to calves of a number of other
      haloalkene cysteine conjugates has been examined to ascertain whether, like DCVC,
      they produce bone marrow and renal injury. Intravenous administration of the N
      acetyl cysteine conjugate of DCVC produced renal but not bone marrow injury at a
      molar equivalent dose to DCVC, indicating that the calf can deacetylate the
      mercapturic acid and further that sufficient chemical had reached the kidney to
      be a substrate for the enzyme cysteine conjugate beta-lyase. However, intravenous
      administration of the alpha-methyl analogue of DCVC, which cannot undergo
      metabolism via the enzyme cysteine conjugate beta-lyase, was without toxicity at
      doses about five-fold higher than DCVC. These latter findings provide strong
      evidence that metabolism of DCVC via the enzyme beta-lyase is necessary for bone
      marrow and renal injury to occur. The cysteine conjugates of perchloroethylene
      and hexachloro-1,3-butadiene(HCBD) when given intravenously to calves at molar
      equivalent doses to DCVC, or above, did not produce either bone marrow or renal
      injury. In contrast, intravenous administration of the cysteine conjugate of
      tetrafluoroethylene (TFEC) produced severe renal tubular injury in calves without
      affecting the bone marrow. In vitro studies with these haloalkene cysteine
      conjugates showed, like DCVC, that they were good substrates for calf renal
      cysteine conjugate beta-lyase and toxic to renal cells as judged by their ability
      to reduce organic anion and cation transport by slices of calf renal cortex and
      inhibit the renal enzyme glutathione reductase. Calves were also dosed either
      orally or intravenously with HCBD to assess its toxicity. HCBD at higher molar
      equivalent doses than DCVC produced mid-zonal necrosis in the liver, renal
      tubular necrosis but no bone marrow injury in calves. The key findings emerging
      from these studies are (1) that none of the other cysteine conjugates, at molar
      equivalent doses to DCVC and above, produce bone marrow injury in calves, (2)
      TFEC produced only renal injury, suggesting that sufficient of the other
      conjugates had not reached the kidney for metabolism by beta-lyase to produce
      cytotoxicity and (3) that HCBD itself is more toxic than its cysteine or
      mercapturic acid conjugate, suggesting that pharmaco-kinetics and disposition are
      important factors in determining the toxicity of these conjugates to calves.
      Further studies are needed to understand the basis for the selective toxicity of
      DCVC to the bone marrow of calves.

PMID- 8870954
TI  - Role of glutathione modulation in acrylonitrile-induced gastric DNA damage in
      rats.
AB  - Acrylonitrile (VCN) or its reactive metabolites irreversibly interact with
      gastric DNA in vivo and cause DNA damage. The effect of glutathione (GSH)
      modulation on VCN-induced genotoxicity and unscheduled DNA repair synthesis
      (UDRS) in DNA of gastric mucosal tissues was investigated. VCN-induced UDRS was
      determined: in control rats, rats with depleted gastric GSH contents, and rats
      treated with sulfhydryl compounds. A single oral dose (23 mg/kg) of VCN induced a
      time- and dose-dependent increase in gastric UDRS and decrease in GSH levels.
      While maximal UDRS in gastric mucosa was observed 2 h following oral
      administration of 23 mg/kg VCN, maximal GSH depletion (50% of control) was
      detected 4 h following treatment. Increasing the VCN dose to 46 mg/kg caused a
      further decrease in gastric GSH level (27% of control), while UDRS was elevated.
      Inhibition of VCN oxidation by treatment of the animals with the cytochrome P450
      inhibitor, SKF 525-A, prior to VCN administration caused 65% reduction in VCN
      induced UDRS. Treatment of rats with the GSH depletor diethylmaleate (DEM) prior
      to VCN administration caused 167% increase in UDRS in gastric mucosal tissues.
      Treatment of the animals with the sulfhydryl compounds, cysteine and
      penicillamine, prior to VCN administration protected against VCN-induced UDRS.
      The results demonstrated an inverse and highly significant correlation between
      gastric GSH levels and VCN-induced UDRS (r = -0.873, P < 0.0001). In conclusion,
      our study indicates that VCN bioactivation and the homeostasis of gastric GSH may
      play a major, role in the initial processes underlying VCN-induced gastric
      carcinogenesis.

PMID- 8870955
TI  - Effects of glutathione and pH on the oxidation of biomarkers of cellular
      oxidative stress.
AB  - Cellular oxidative stress is associated with such pathological conditions as
      arteriosclerosis, inflammatory diseases and cancer. The oxidation of the
      biomarkers. 2',7'-dichlorofluorescin (DCFH), 2-deoxyribose, and lipid
      peroxidation are often used to assess the status of oxidative stress in cells and
      tissues. Since high levels of reduced glutathione (GSH) and acidic conditions
      have been associated with diminished chemical lethality, we evaluated the
      influence of these parameters on the cellular response to oxidative stress. We
      used a cultured hepatocyte line (ch/ch cells) that is susceptible to oxidative
      toxicity. A hydroxyl radical-generating system consisting of H2O2, ascorbate and
      iron produced a pH-dependent lethality, with complete cell killing at pH 7.4 and
      none at pH 6.8. Lethality correlated with the depletion of intracellular GSH, and
      with an increase in DNA fragmentation. The influence of GSH and pH was assessed
      for DCFH and 2-deoxyribose oxidation, and for lipid peroxidation. The oxidation
      of DCFH and 2-deoxyribose was inhibited by GSH, with about 4-fold greater
      inhibition efficacy at pH 6.8 than at pH 7.4 [IC50 values (microM GSH) for pH 6.8
      and 7.4, respectively: DCFH = 7 and 30; 2-deoxyribose = 125 and 490]. GSH did not
      affect lipid peroxidation at either pH, even at a high intracellular
      concentration of 10 mM. We conclude: 1) GSH is not inhibiting DCFH and 2
      deoxyribose oxidation by simply quenching reactive oxygen (hydroxyl radical or
      perferryl oxygen), since GSH did not inhibit lipid peroxidation: 2) the
      protonated form GSH is more likely to be the inhibitory species rather than GS-,
      since even in the simple cell-free systems lower pH inhibited biomarker
      oxidation; and; 3) hydroxyl radical may not be the primary intracellular oxidant
      of DCFH, since intracellular GSH concentrations are typically 10- to 100-fold
      higher than the IC50 values for GSH inhibiting reactive oxygen-mediated DCFH
      oxidation.

PMID- 8870956
TI  - Urinary excretion of N-acetyl-S-allyl-L-cysteine upon garlic consumption by human
      volunteers.
AB  - N-Acetyl-S-allyl-L-cysteine (allylmercapturic acid, ALMA) was previously detected
      in urine from humans consuming garlic. Exposure of rats to allyl halides is also
      known to lead to excretion of ALMA in urine. ALMA is a potential biomarker for
      exposure assessment of workers exposed to allyl halides. It is not known whether
      garlic consumption can lead to urinary concentrations of ALMA which may interfere
      with biological monitoring of exposure to allyl halides by determination of
      urinary ALMA. Therefore, this study was undertaken to determine the cumulative
      excretion and the excretion kinetics of ALMA in urine of humans consuming garlic.
      Six human volunteers were given orally two garlic tablets, each containing 100 mg
      garlic extract (each representing 300 mg fresh garlic). Three of the volunteers
      consumed additional garlic after the garlic tablet intake. Urine samples were
      collected up to 24 h after the intake of the garlic tablets. ALMA was identified
      in the urine using gas chromatography-mass spectrometry (GC-MS) and determined
      quantitatively with a limit of detection of 0.10 microgram/ml with gas
      chromatography with sulphur selective detection. The total amount of ALMA found
      in urine of volunteers who consumed two garlic tablets was 0.43 +/- 0.14 mg (n =
      3). In the urine of the three volunteers who consumed not only two garlic tablets
      but also additional fresh garlic, a significantly higher amount of ALMA was
      excreted in the urine, 1.4 +/- 0.2 mg (n = 3). The elimination half-life of ALMA,
      estimated from urinary excretion rate versus time curves, was 6.0 +/- 1.3 h (n =
      5). One volunteer, who ate additional garlic, showed an irregular elimination
      profile and was excluded from this estimation. The highest urinary concentration
      of ALMA found in this study was 2.2 micrograms/ml. In a preliminary biological
      monitoring study of exposure in workers with potential exposure to allyl chloride
      (AC) up to the occupational exposure limit of 1 ppm (8-h TWA), we recently found
      urinary ALMA concentrations up to 4 micrograms/ml. Based on the results presented
      here, we conclude that garlic consumption is a potential confounder when
      monitoring human exposure to allylhalides and other chemicals leading to ALMA
      excretion when ALMA is used as a biomarker of exposure.

PMID- 8870957
TI  - Inhibitory effect of atractylon on tert-butyl hydroperoxide induced DNA damage
      and hepatic toxicity in rat hepatocytes.
AB  - Atractylon, a main sesquiterpenic constituent of Atractylodes rhizomes, was
      studied for the mechanism of its inhibitory effects on the tert-butyl
      hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in primary
      culture of rat hepatocytes. In the preliminary study, atractylon showed an
      effective antioxidant property tested by its capacity for quenching 1,1-diphenyl
      2-picrylhydrazyl radical (DPPH). Further investigations showed that atractylon at
      the concentrations of 0.01, 0.1 and 1.0 mg/ml decreased the formation of
      malondialdehyde (MDA), leakage of lactate dehydrogenase (LDH) and alanine
      aminotransferase (ALT) and repair synthesis of DNA induced by 30-min treatment of
      t-BHP (1.5 mM) in primary cultured rat hepatocytes. Addition of atractylon also
      attenuated the genotoxicity of t-BHP evaluated by unscheduled DNA synthesis. The
      sum of the results suggested that the protective effect of atractylon against
      oxidative stress induced by t-BHP is via its ability to quench free radicals.

PMID- 8870958
TI  - Lack of cardiotoxicity of a new antineoplastic agent, a synthetic derivative of
      indenoisochinoline: comparison with daunorubicin in rabbits.
AB  - The effect of repeated i.v. administration (once weekly, 12 administrations) of a
      new antineoplastic agent, Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5, 11-dioxo
      5,6-dihydro-11 H-indeno [1,2-c]-isochinoline hydrochloride, 10 mg/kg) and
      daunorubicin (3 mg/kg) were investigated in rabbits in vivo. The criterion of
      occurrence of cardiotoxicity was compared with a control group of animals.
      Noninvasive polygraphic records were used to evaluate the function of the heart.
      The morphological changes of the heart were evaluated after the death of animals.
      There were no significant changes found in the ratio of the pre-ejection
      period/left ventricular ejection time (PEP: LVET ratio) after administration of
      Oracin (values between 0.3080 and 0.3310) or in the control group (values between
      0.3425 and 0.3885). The administration of daunorubicin induced a significant,
      progressive increase in the PEP: LVET ratio (0.3775-0.9473), which was
      significantly different both from the Oracin-treated and the control group of
      animals. Histological examination of the hearts from the control group revealed
      normal structure of the myocardium including minute changes (dispersed
      cardiomyocytes with intensively eosinophilic cytoplasm, and several single cells
      with degenerated myofibrils) similar to the normal changes in muscle tissue. A
      very similar scenario was found in the Oracin group with the exception of one
      case where a slightly higher number of degenerated and necrotic cells was
      occurring. Administration of daunorubicin resulted in severe dispersed damage of
      the myocardium (myocytolysis with subsequent interstitial fibrosis), the changes
      being markedly different from those of the Oracin treatment and the control
      group. On the basis of our results it is possible to conclude that the
      administration of Oracin (10 mg/kg i.v.) did not induce signs of cardiotoxicity
      in rabbits in vivo.

PMID- 8870959
TI  - Modulation of serotonin-induced currents by metals in mouse neuroblastoma cells.
AB  - The effects of several metals on the serotonin receptor-channel complex were
      studied using mouse neuroblastoma N1E-115 cells which are known to be endowed
      with the 5-HT3 subclass of the receptor. The whole-cell patch clamp technique was
      used to record currents induced by serotonin at a concentration of 3 microM which
      was equivalent to the apparent dissociation constant. Methylmercury and mercuric
      chloride suppressed serotonin-induced currents irreversibly, with a 50%
      suppression being observed at concentrations of 3 microM and 2 microM,
      respectively. Lead and zinc suppressed the current with IC50S of 80 microM and 50
      microM, respectively, and the effects of both metals were reversible after
      washing with metal-free solution. Lanthanum also suppressed the current with an
      IC50 of 10 microM, and the effect was partially reversible. Cadmium and cobalt
      augmented serotonin-induced currents slightly but consistently at a concentration
      of 100 microM, and the effect was reversible. Aluminum at 100 microM, had no
      effect on serotonin-induced currents. It was concluded that the 5-HT3 receptor is
      endowed with a unique property with respect to the actions of metals which is not
      shared by some other ligand-gated and voltage-gated ion channels.

PMID- 8870960
TI  - Host resistance to rat cytomegalovirus (RCMV) and immune function in adult PVG
      rats fed herring from the contaminated Baltic Sea.
AB  - The immunotoxic potential of many classes of environmental contaminants has been
      well established in laboratory studies, with much attention being focussed on
      aryl hydrocarbon (Ah)-receptor binding polychlorinated biphenyl (PCB),
      polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF)
      congeners. In a semi-field study, we previously showed that harbour seals (Phoca
      vitulina) fed herring from the contaminated Baltic Sea had lower natural killer
      cell activity, T-lymphocyte functionality and delayed-type hypersensitivity
      responses than seals fed herring from the relatively uncontaminated Atlantic
      Ocean. While ethical and practical constraints preclude in-depth studies in
      seals, specific reagents and a wider array of immune function tests allow such
      studies in laboratory rats. We therefore carried out a feeding study in rats
      aimed at extending our observations of contaminant-induced immunosuppression in
      harbour seals. The same two herring batches used in the seal study were freeze
      dried, supplemented and fed to female adult PVG rats for a period of 4 1/2
      months. Daily contaminant intakes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      toxic equivalents (TEQ) were estimated to be 0.3 ng/kg body weight and 1.6 ng/kg
      in the Atlantic and Baltic groups, respectively. At the end of the feeding
      experiment, no contaminant-related changes in spleen CD4+/CD8+ cellularity,
      natural killer cell activity, or mitogen-induced proliferative responses of
      thymus or spleen cells could be detected. However, total thymocyte numbers and
      thymus CD4+/CD8+ ratios were reduced in the Baltic group. A novel model was
      established to assess the specific T-cell response to rat cytomegalovirus (RCMV).
      When applied to the feeding study, no differences between the Atlantic and Baltic
      groups in the RCMV-induced proliferative T-lymphocyte responses could be
      detected, but virus titres in salivary glands of infected rats of the Baltic Sea
      group were higher. These elevated RCMV titres and changes in thymus cellularity
      suggest that the dietary exposure to low levels of contaminants may have been
      immunotoxic at a level which our immune function test could not otherwise detect.
      While the herring diet per se appeared to have an effect on several immune
      function parameters, lower plasma thyroid hormone levels in the Baltic Sea group
      of rats confirmed that exposure to the environmental mixture of contaminants led
      to adverse PHAH-related health effects.

PMID- 8870961
TI  - Cyclophosphamide-induced apoptosis induces phocomelia in the mouse.
AB  - Phocomelia (absence of upper fore and/or hind limbs) was induced in mouse fetuses
      using cyclophosphamide. On day 11 of gestation, pregnant mice were injected
      intraperitoneally with 10 ml/kg of saline containing cyclophosphamide (CP) at a
      dosage of 20 mg/kg body weight. On day 18, the fetuses were removed by Caesarean
      section from dams given CP on day 11 and were examined for external anomalies. Of
      22 fetuses from CP-treated dams, 13 were dead or absorbed, but the surviving 9
      fetuses were found to have phocomelia with various other external anomalies. In
      order to examine the direct cytotoxic effect of CP on fetal limb buds, fetuses
      were removed at 8, 16, 24, and 48 h after CP administration on day 11, revealing
      the presence of frequent pyknotic nuclei and apoptotic bodies in hematoxylin and
      eosin (H & E) preparations. Cell-nuclei and apoptotic bodies were frequently
      observed by nick end-labeling in limb buds. Transmission electron microscopy
      demonstrated the typical changes of apoptosis. DNA extracted from the fetal limb
      buds submitted to CP was analysed by agarose gel electrophoresis, showing the
      ladder pattern characteristic of internucleosomal cleavage. These findings
      suggest that cyclophosphamide causes apoptosis in mouse fetal limb buds and that
      this process induces the external anomalies of phocomelia.

PMID- 8870962
TI  - Toxicity of fungicides containing ethylene-bis-dithiocarbamate in serumless
      dissociated mesencephalic-striatal primary coculture.
AB  - Agricultural exposure to the organomanganese fungicide MANEB (manganese-ethylene
      bis-dithiocarbamate) may induce an extrapyramidal syndrome resembling
      parkinsonism. To evaluate the relative role of manganese (Mn) and ethylene-bis
      dithiocarbamate (EBDTC) in the hazard of organomanganese fungicides, we studied
      the effects of MANCOZEB (Mn-Zinc-EBDTC) and ZINEB (Zinc-EBDTC) on serumless
      dissociated mesencephalic-striatal primary coculture. High affinity 3H-dopamine
      (DA) and 14C GABA uptakes as well as immunocytochemical staining of tyrosine
      hydroxylase (TH)-containing cells were used as specific functional markers of DA
      and GABA neuron viability. Both MANCOZEB and ZINEB, at 10 and 50 microM
      concentrations, dose dependently reduced DA and GABA viability parameters. These
      data suggest that EBDTC rather than Mn may be primarily responsible for the
      cytotoxicity of organomanganese fungicides on neuronal systems relevant to the
      pathophysiology of parkinsonism.

PMID- 8870963
TI  - Machine learning techniques in early screening for gastric and oesophageal
      cancer.
AB  - A database on 2692 dyspeptic patients over the age of 40 was established,
      consisting of 73 epidemiological and clinical variables. A tree-based machine
      learning algorithm (PREDICTOR) was applied to this database, in order to attempt
      to find rules which would classify patients into 2 groups, i.e., those suffering
      from gastric or oesophageal cancer, and the remainder. The results were
      encouraging. The cross-validated classification performance figure showed that by
      classifying 61.3% of the patients as high risk, a sensitivity of 94.9% and a
      specificity of 39.8% could be achieved. It is planned to construct an expert
      system based on the rules produced by the machine learning algorithm, in order to
      provide preliminary screening for cancer in dyspeptic patients.

PMID- 8870964
TI  - The interpretation of time-varying data with DIAMON-1.
AB  - Applying the methods of Artificial Intelligence to clinical monitoring requires
      some kind of signal-to-symbol conversion as a prior step. Subsequent processing
      of the derived symbolic information must also be sensitive to history and
      development, as the failure to address temporal relationships between findings
      invariably leads to inferior results. DIAMON-1, a framework for the design of
      diagnostic monitors, provides two methods for the interpretation of time-varying
      data: one for the detection of trends based on classes of courses, and one for
      the tracking of disease histories modelled through deterministic automata. Both
      methods make use of fuzzy set theory taking account of the elasticity of medical
      categories and allowing discrete disease models to mirror the patient's
      continuous progression through the stages of illness.

PMID- 8870965
TI  - Retrieval of clinical science information using an interactive activation and
      competition network.
AB  - A method for storing and retrieving tabulated clinical science information is
      described. This method uses the interactive activation and competition network
      and belongs to the realm of parallel distributed processing. The advantages of
      this method are that information is readily retrievable by name and by any
      content, and that the best matched information is automatically returned when
      partially incorrect cues are given. Furthermore, it allows a variable degree of
      association among different units of information. The basic principles of this
      method are illustrated through a simple example from clinical bacteriology. In
      addition an application of this method to the retrieval of information in
      cardiology is presented.

PMID- 8870966
TI  - Fuzzy gating and the problem of screening.
AB  - The problem of population screening is very important for medical statistics. It
      allows one to analyze the expression of certain parameters in the population of
      healthy persons, in order to compare it to the expression of these parameters in
      the persons with a specific disease. If a parameter is expressed differently in
      ill and healthy persons, then this parameter may serve as a pointer to the
      disease, especially in its earlier stages. While the analysis of given parameters
      in people with the established diagnosis does not represent many difficulties,
      the analysis of the general population is not easily carried out. The problem is
      that the general population contains both ill and healthy people. The population
      of healthy people is said to be 'contaminated' by the noise-subpopulation of ill
      people. The resulting statistical parameters are, therefore, biased and in order
      to find their correct values one needs to cancel out the input of the noise. In
      this paper we propose a new method to cancel out the noise, based on the theory
      of fuzzy sets. We assume that an auxiliary parameter is measured simultaneously
      and it is used to separate the subpopulations. If two subpopulations (the data
      and the noise) form clearly distinguished clusters in respect to this auxiliary
      parameter, one creates a gate and throws out the events outside the gate assuming
      that they are noise. However, when the clusters overlap, this procedure is no
      longer useful, and it is this particular situation for which we have developed
      fuzzy gating. In addition to the fact that the gate is fuzzified, a specifically
      designed algorithm is applied to compute the probability density functions for
      both subpopulations. Our algorithm gives a very high precision and is very robust
      as to the level of noise and the type of distributions.

PMID- 8870967
TI  - Sleep classification in infants by decision tree-based neural networks.
AB  - This paper presents an AI-based approach to automatic sleep stage scoring. The
      system TBNN (Tree-Based Neural Network) uses a decision-tree generator to provide
      knowledge that defines the architecture of a backpropagation neural network,
      including feature selection and initialisation of the weights. The case study
      reports a successful application to the data from polygraphic all-night sleep of
      8 babies aged 6 months. The teaching input was provided by a medical expert in
      accordance with the rules of Guilleminault and Souquet. The performance of TBNN
      is compared with 5 other methods and the results are discussed.

PMID- 8870968
TI  - Application of the fuzzy ARTMAP neural network model to medical pattern
      classification tasks.
AB  - This paper presents research into the application of the fuzzy ARTMAP neural
      network model to medical pattern classification tasks. A number of domains, both
      diagnostic and prognostic, are considered. Each such domain highlights a
      particularly useful aspect of the model. The first coronary care patient
      prognosis, demonstrates the ARTMAP voting strategy involving 'pooled' decision
      making using a number of networks, each of which has learned a slightly different
      mapping of input features to pattern classes. The second domain, breast cancer
      diagnosis, demonstrates the model's symbolic rule extraction capabilities which
      support the validation and explanation of a network's predictions. The final
      domain, diagnosis of acute myocardial infarction, demonstrates a novel category
      pruning technique allowing the performance of a trained network to be altered so
      as to favour predictions of one class over another (e.g. trading sensitivity for
      specificity or vice versa). It also introduces a 'cascaded' variant of the voting
      strategy intended to allow identification of a subset of cases which the network
      has a very high certainty of classifying correctly.

PMID- 8870969
TI  - Genomic organization of the mouse beta 1 gene: conservation of the beta 1D but
      not of the beta 1B and beta 1C integrin splice variants.
AB  - We have determined the genomic organization of the 3'-region of the murine beta 1
      gene and cloned the murine beta 1D integrin splice variant. Overlapping genomic
      clones encompassing the region of the beta 1D-specific exons were isolated from a
      phage lambda FIXII library, mapped and partially sequenced. All of the exon
      intron junctions identified in the murine beta 1 gene fit with the consensus
      splice donor and acceptor sequences and occur at the same positions as in their
      human counterparts. cDNA clones for the beta 1D integrin were isolated from a
      murine skeletal muscle library. The human and murine beta 1D sequences are
      conserved at the nucleotide (93%) and amino acid (100%) level, suggesting an
      important role of this muscle-specific variant throughout mammalian phylogenesis.
      In contrast, murine sequences for beta 1B are very different from human beta 1B
      at both the nucleotide as well as amino acid level. Moreover, no specific
      polyadenylation signal for the beta 1B variant could be identified in genomic
      clones, suggesting that this variant is not present in the mouse. Finally, we
      were not able to identify a murine beta 1C splice variant by sequencing analysis,
      Southern hybridization techniques or polymerase chain reaction of mRNA from
      platelets. These findings indicate that the beta 1B and beta 1C variants emerged
      relatively late in the phylogenesis of the beta 1 integrin family.

PMID- 8870970
TI  - Cadherin-mediated adhesion is required for normal growth regulation of human
      gingival epithelial cells.
AB  - The cadherins are a family of cell membrane proteins that mediate calcium
      dependent cell-cell adhesion. E-cadherin is required for the formation,
      differentiation, polarization and stratification of epithelia; P-cadherin is also
      expressed on many epithelia. We report here the first study of cadherin
      expression in immortalized human gingival epithelial cells (IHGK) and examine the
      role of cadherins in growth regulation of these cells. We found that the IHGK
      cells are similar to normal gingival epithelial cells in their cadherin
      expression and density-dependent inhibition of growth. The IHGK cells proliferate
      more rapidly at low calcium concentration (0.15 mM) than at physiological
      concentrations of calcium (1.8 mM) and magnesium (0.65 mM; Ca/Mg medium)
      suggesting that calcium is required for density-dependent regulation of
      proliferation. To evaluate the possibility that cadherin function is required for
      contact inhibition in these cells, we grew them in Ca/Mg medium in the presence
      of adhesion-blocking anti-cadherin monoclonal antibodies. At anti-E-cadherin
      concentrations sufficient to disrupt cell-cell adhesion, the proliferation of the
      IHGK cells was similar to that observed in medium containing 0.2 mM EDTA. Anti-P
      cadherin had a much weaker effect on cell proliferation than anti-E-cadherin, and
      cells grown in medium containing both antibodies grew at intermediate rates. The
      increased proliferation of the IHGK cells in either low calcium medium or Ca/Mg
      medium containing adhesion-blocking anti-cadherin antibodies suggests that
      cadherin-mediated adhesion is required for density-dependent regulation of growth
      of these cells.

PMID- 8870971
TI  - Serine 752 in the cytoplasmic domain of the beta 3 integrin subunit is not
      required for alpha v beta 3 postreceptor signaling events.
AB  - A naturally occurring point mutation (Ser752Pro substitution) in the beta subunit
      cytoplasmic domain of the platelet fibrinogen receptor GPIIb-IIIa (integrin alpha
      IIb beta 3), causing Glanzmann's thrombasthenia, has been shown to abrogate
      bidirectional transmembrane signaling of GPIIb-IIIa when expressed in
      heterologous cells (Chen YP, 1994, Blood 84, 1857-1865). As the vitronectin
      receptor alpha v beta 3 constitutively mediates cell attachment to RGD containing
      extracellular matrix proteins, the purpose of this study was to explore the
      regulatory role of Ser752 in alpha v beta 3 vitronectin receptor function, by
      cotransfecting recombinant human alpha v cDNA together with human beta 3 mutant
      cDNA into Chinese hamster ovary (CHO) cells. CHO cells expressing wild type human
      alpha v beta 3 acquired the ability to attach and spread on fibrinogen and von
      Willebrand factor, in contrast to non transfected CHO cells that only bound to
      vitronectin and fibronectin. Overexpression of a truncated recombinant beta 3
      subunit (beta 3 delta 744) generated alpha v (hamster) beta 3 (human) chimers
      that mediated attachment but lost the ability to promote cell spreading on
      vitronectin, von Willebrand factor and fibrinogen, and to concentrate in focal
      contact sites, demonstrating a negative effect of beta 3 delta 744 on alpha v
      beta 3 dependent postreceptor occupancy events. Transfection of beta 3Ser752Pro
      reproduced the same negative effect as beta 3 delta 744, whereas beta 3Ser752Ala
      restored normal receptor function by allowing pronounced attachment and spreading
      on fibrinogen and von Willebrand factor. Our results provide evidence that (1)
      the C-terminal cytoplasmic domain of beta 3 (amino acids 744-762) is essential
      for alpha v beta 3 integrin postreceptor occupancy events; (2) within this
      domain, the Ser752Pro mutation affects alpha v beta 3 postreceptor occupancy
      events by preventing cell spreading and focal contact localization; (3) the
      defective receptor function of the vitronectin receptor alpha v beta 3 is due to
      the presence of Pro752, rather than the absence of Ser752, as a Ser to Ala
      substitution at position 752 restores normal beta 3 integrin cell spreading and
      adhesive plaque formation.

PMID- 8870972
TI  - Reduction of tumorigenicity by alpha 3 integrin in a rhabdomyosarcoma cell line.
AB  - The expression levels of integrin adhesion receptors have often been correlated
      with neoplastic transformation and invasiveness. To investigate more definitively
      the role of the integrin VLA-3 (alpha 3 beta 1) in tumor cell behavior, we
      transfected alpha 3 subunit cDNA into human rhabdomyosarcoma (RD) cells.
      Transfectants expressing high levels of alpha 3 beta 1 on their cell surface
      displayed an altered morphology and decreased anchorage-dependent growth in
      vitro. Cells expressing alpha 3 also displayed marked reduction in anchorage
      independent growth in soft agar and in their ability to form tumors when injected
      subcutaneously into athymic nude mice. Thus, VLA-3 can repress the transformed
      phenotype of rhabdomyosarcoma tumor cells. Similar changes in morphology and
      growth characteristics were observed in cells expressing a chimeric molecule X3C4
      in which the alpha 3 cytoplasmic domain had been exchanged with that of the alpha
      4 integrin subunit. Therefore, alpha 3 inhibitory effects in RD cells appear not
      to require specific signalling through the alpha 3 cytoplasmic domain.

PMID- 8870973
TI  - Tight junction dynamics in the frog urinary bladder.
AB  - In a previous study in frog skin (Castro et al., J. Memb. Biol. 134:15-29, 1993),
      it was shown that TJs experimentally disrupted by a selective deposition of BaSO4
      could be resealed upon addition of Ca2+ to the apical solution; in the absence of
      apical Ca2+, the normal Ca2+ activity of the Na2SO4-Ringer's bathing the
      basolateral side was not able to induce TJ resealing. We now show that apical
      Ca2+ also activates the TJ sealing mechanism in frog urinary bladders. Three
      known procedures were utilized to increase TJ permeability, all in the absence of
      apical Ca2+: (i) exposure to high positive transepithelial clamping potentials;
      (ii) exposure of the apical surface to hypertonic solutions; and (iii) selective
      deposition of BaSO4 in the TJs. The resealing of the TJs was promoted by raising
      the concentration of Ca2+ in the apical solution. This effect of Ca2+ is not
      impaired by the presence of Ca2+ channel blockers (nifedipine, verapamil, Mn2+ or
      Cd2+) in the apical solution, indicating that junction resealing does not depend
      on Ca2+ entering the cells through the apical membrane. TJ resealing that occurs
      in response to raised apical Ca2+ most likely results from a direct effect of
      Ca2+, entering the disrupted TJs from the apical solution and reaching the zonula
      adhaerens Ca2+ receptors (E-cadherins). Protein kinase C (PKC) must play a
      significant role in the control of TJ assembly in this tight epithelia since the
      PKC inhibitor (H7) and the activator (diC8) markedly affect TJ recovery after
      disruption by apical hypertonicity. H7 treated tissues show marked recuperation
      of conductance even in the absence of apical Ca2+. In contrast, diC8 prevents
      tissue recuperation which normally occurs after addition of Ca2+ to the apical
      solution.

PMID- 8870974
TI  - Periinfarct depolarizations.
AB  - In the surroundings of focal ischemic lesions, repetitive spreading depression
      (SD)-like depolarizations occur. These depolarizations are triggered by the
      anoxic release of potassium and excitatory amino acids from the infarct core, and
      they are propagated over the whole hemisphere at a speed of approximately 3
      mm/min. The associated fluid shifts can be detected by diffusion-weighted
      magnetic resonance imaging (MRI) and correlate with an aggravation of the
      metabolic disturbance. In the peripheral, normally perfused brain regions of the
      infarcted hemisphere, the metabolic workload of SD is coupled to a parallel
      increase of blood flow, ensuring undisturbed oxygen supply. In the periinfarct
      penumbra, in contrast, the reduced hemodynamic capacity of the collateral system
      prevents adequate oxygenation and results in episodes of tissue hypoxia.
      Periinfarct SDs induce expression of immediate early genes in all brain regions
      except the ischemic core, i.e, in the penumbra and the surrounding normal brain
      tissue. In the penumbra, the hypoxic episodes evoked by SDs produce an additional
      stress response that is reflected by the expression of stress proteins and the
      suppression of global protein synthesis. In the most severely ischemic parts of
      the penumbra, periinfarct depolarizations may turn into terminal depolarization,
      resulting in a stepwise expansion of the infarct core. Postischemic application
      of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists
      suppresses periinfarct depolarizations, reverses the penumbral suppression of
      protein synthesis, and reduces infarct size. These observations demonstrate that
      periinfarct depolarizations aggravate focal ischemic injury and suggest that
      therapeutic suppression of these depolarizations minimizes infarct size.

PMID- 8870975
TI  - Perfluorochemical oxygen carriers: potential uses in neurosciences.
AB  - In this article we review recent developments in the field of "first-" and
      "second-generation" perfluorochemical (PFC) oxygen carriers. Particular emphasis
      is placed on the latest research and its implications regarding the clinical and
      experimental neurosciences. These compounds are ideally suited to the
      transportation of O2 within the vascular system. Two properties that facilitate
      their use in this respect are their very high solubility coefficients for O2 and
      CO2 and their biological inertness. Unfortunately, their widespread use has been
      limited by logistical difficulties associated particularly with their molecular
      behavior in vivo. However, advances in PFC technology have led to renewed
      interest. A potential role for second-generation PFCs in cerebral protection is
      exciting. Other possible significant applications are slowly becoming established
      in clinical practice. Currently under investigation are potential uses in the
      management of severe head injuries, radiotherapy or chemotherapy of malignant
      brain tumors, protection against air embolism, preservation of organs for
      transplantation, and as a tool in microsurgery of the retina or other parts of
      the CNS. Diagnostic neuroimaging applications could include the employment of
      PFCs as adjuncts in ultrasound, Doppler, computed tomography (CT), and magnetic
      resonance (MR) to achieve enhanced imaging and precise staging of inflammatory,
      neoplastic, and vascular disease processes. Research applications could include
      their use in magnetic resonance imaging and spectroscopy in assessing cerebral
      blood flow, local oxygen tension, and brain metabolism, in molecule-specific
      imaging, and as physiological markers of O2, ions, and pH.

PMID- 8870976
TI  - Cortical thermal clearance as a predictor of imminent neurological deterioration.
AB  - Cerebral blood flow (CBF) is vital for the perfusion of brain tissue. It is
      frequently deranged in acute neurosurgical disorders, particularly subarachnoid
      haemorrhage and head injury. Despite its importance, in clinical practice the
      routine measurement of CBF is uncommon, as changes in CBF can occur abruptly.
      However, a method of CBF monitoring may be potentially useful, particularly if
      warning could be obtained of impending ischaemia before neurological
      deterioration. Measurement of tissue thermal clearance has been used as an
      estimate of local tissue blood flow since 1933. Its history is full of
      controversy, mostly centred around quantification. The ability of perfused
      tissues to clear heat is, as a first approximation, the sum of two components: a
      fixed component related to the constituents of the tissue, primarily the water
      content, and a variable convective component, related to the local blood flow.
      The mathematical relationship between flow and the observed increment in thermal
      clearance is still debatable. Here, the history of thermal clearance is reviewed,
      and the results of our work with a relatively simple device are described. It
      consisted of an implantable probe, designed to measure the thermal clearance of
      the cortical surface in arbitrary clearance units (CU), ranging from 27 CU
      (cadaveric) to 69 CU (well perfused brain). Pre- and postoperative studies showed
      that the system was capable of following changes in blood flow rapidly. The
      cortical thermal clearance (CTC) was monitored postoperatively in 24 patients
      after aneurysm surgery. Most remained clinically stable and had thermal
      clearances over 50 CU. In others, however, it was seen that a low-or falling
      thermal clearance was associated with development of a neurological deficit.
      Analysis using receiver operating characteristics curves established that the
      method had a sensitivity of 0.86 and a specificity of 0.82 in the detection of a
      contralateral ischaemic motor deficit. No patient in whom the CTC remained above
      50 CU ever developed a new neurological deficit, whereas all patients with a CTC
      below 35 did. The evidence-historical, mathematical, practical, and theoretical
      that CTC is closely related to local blood flow is discussed. Changes in thermal
      clearance have been observed prior to the development of ischaemic neurological
      deterioration. Detection of imminent ischaemia may become increasingly important
      as means of improving cortical blood flow become more widely available. Whether
      such early detection- and subsequent treatment-of ischaemia will result in better
      patient outcome remains to be established. I believe it will.

PMID- 8870977
TI  - Influence of tertiary structure on nucleophilic substitution reactions of
      proteins.

PMID- 8870978
TI  - The involvement of cytochrome P450 peroxidase in the metabolic bioactivation of
      cumene hydroperoxide by isolated rat hepatocytes.
AB  - Organic hydroperoxides are believed to be primarily detoxified in cells by the
      GSH peroxidase/GSSG reductase system and activated to cytotoxic radical species
      by non-heme iron. However, organic hydroperoxides seem to be bioactivated by
      cytochrome P450 (P450) in isolated hepatocytes as various P450 (particularly P450
      2E1) inhibitors inhibited cumene hydroperoxide (CumOOH) metabolism and attenuated
      subsequent cytotoxic effects including antimycin A-resistant respiration, lipid
      peroxidation, iron mobilization, ATP depletion, and cell membrane disruption.
      CumOOH metabolism was also faster in P450 1A-induced hepatocytes and was
      inhibited by the P450 1A inhibitor alpha-naphthoflavone. The ferric chelator
      deferoxamine also prevented cytotoxicity even after CumOOH had been metabolized
      but had no effect on CumOOH metabolism. This emphasizes the toxicological
      significance of the iron released following hydroperoxide metabolic activation by
      cytochrome P450. The radical trap, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl
      (TEMPO), had no effect on CumOOH metabolism but prevented CumOOH-induced
      antimycin A-resistant respiration, lipid peroxidation, iron mobilization, and
      loss of membrane integrity. These results suggest that CumOOH is metabolically
      activated by some P450 enzymes (e.g., P450 2E1) in hepatocytes to form reactive
      radical metabolites or oxidants that cause lipid peroxidation and cytotoxicity.

PMID- 8870979
TI  - Inhibition of N-nitrosodimethylamine demethylase in rat and human liver
      microsomes by isothiocyanates and their glutathione, L-cysteine, and N-acetyl-L
      cysteine conjugates.
AB  - Natural and synthetic isothiocyanates and their conjugates were examined for
      their inhibitory effects toward rat and human liver microsomal N
      dimethylnitrosoamine demethylase (NDMAd) activity using a radiometric NDMAd
      assay. Substrate concentrations of 30 and 60 microM were used to probe the
      activity of cytochrome P4502E1 isozyme through the alpha-hydroxylation of NDMA.
      It was found that alkyl isothiocyanates such as sulforaphane and allyl
      isothiocyanate displayed very weak inhibition, whereas the arylalkyl
      isothiocyanates such as benzyl and phenethyl isothiocyanate showed significant
      inhibition toward rat liver NDMAd activity with IC50 values of 9.0 and 8.3
      microM, respectively. More interestingly, glutathione conjugates of benzyl,
      phenethyl, and 6-phenylhexyl isothiocyanates all inhibited NDMAd at the
      comparable concentrations. In the phenethyl isothiocyanate conjugates series,
      there exist marked differences in their inhibitory activity; i.e., its conjugates
      with L-cysteine (IC50 = 4.3 microM) and with glutathione (IC50 = 4.0 microM) are
      more potent than its conjugate of N-acetylcysteine (IC50 = 24.0 microM). The same
      trend was also observed for the human liver microsomal NDMAd activity. The half
      lives of these conjugates were determined in the presence of other free thiols
      from L-cysteine or glutathione using an HPLC system. It was shown that
      isothiocyanates are released from their conjugates and react with the free thiols
      present in the solution. The longer half-life of N-acetylcysteine conjugate of
      phenethyl isothiocyanate as compared to the other conjugates is consistent with
      its lower inhibitory activity. The inhibition of NDMAd, and therefore cytochrome
      P4502E1, by isothiocyanate conjugates is most likely due to the action of the
      free isothiocyanates released from the conjugates. Since cytochrome P4502E1 and
      other isozymes play important roles in the activation of the tobacco-specific
      nitrosoamines, these results provide a basis for investigating the potential of
      isothiocyanate conjugates as chemopreventive agents.

PMID- 8870980
TI  - The design of agents to control DNA methylation adducts. Enhanced major groove
      methylation of DNA by an N-methyl-N-nitrosourea functionalized phenyl neutral red
      intercalator.
AB  - An N-methyl-N-nitrosourea (MNU) moiety [CH3N(N=O)C(=O)NH-] linked to the C4'
      position of the 5-substituted phenyl ring of phenyl neutral red (PNR), 2-methyl-3
      amino-5-[p-[[2-[(N-nitroso-N-methylcarbamoyl)amino]ethy l] carbamoyl]phenyl]-7
      (dimethylamino)phenazenium chloride (MNU-PNR), has been synthesized as an
      approach to design a molecule that will deliver alkylating agents with some
      preference to guanine (Gua) in the major groove of DNA. The PNR nucleus was
      chosen because previous studies suggested the following: (1) PNR binds with a
      slight preference for G/C rich sequences; and (2) PNR intercalates into DNA from
      the major groove with the 5-phenyl ring pointing out into the major groove
      (Muller, W., Bunemann, H., and Dattagupta, N. (1975) Eur. J. Biochem. 54, 279
      291). It is demonstrated that MNU-PNR yields 2.6 and 6.0 times more N7
      methylguanine (7-MeGua) than MNU at low salt (10 mM Tris buffer) and high salt
      (10 mM Tris buffer + 200 mM NaCl), respectively. It is also shown that the ratio
      of 7-MeGua (a major groove adduct) to N3-methyladenine (a minor groove adduct) is
      approximately 5 times higher for MNU-PNR than for MNU. The yield of the 7-MeGua
      adduct is decreased by the coaddition of a nonmethylating analogue of MNU-PNR or
      NaCl, but increased in the presence of the minor groove intercalator, ethidium
      bromide. Using a 32P-end-labeled restriction fragment, the enhanced methylation
      by MNU-PNR at 7-Gua is confirmed, and it is demonstrated that the sequence
      dependent formation of 7-MeGua from MNU-PNR is the same as that seen with MNU.
      UV, circular dichrosism, and viscosity studies are consistent with MNU-PNR
      binding to DNA via an intercalation-based process.

PMID- 8870981
TI  - Pyridyloxobutylation of guanine residues by 4-[(acetoxymethyl)nitrosamino]-1-(3
      pyridyl)-1-butanone generates substrates of O6-alkylguanine-DNA alkyltransferase.
AB  - Pyridyloxobutylation of DNA yields adducts that react with O6-alkylguanine-DNA
      alkyl-transferase (AGT) to prevent the repair of O6-methylguanine (O6-mG). The
      chemical characterization of pyridyloxobutyl adducts has been confounded by their
      instability under DNA hydrolysis conditions. They decompose to 4-hydroxy-1-(3
      pyridyl)-1-butanone (HPB) during the chemical or enzymatic hydrolysis of DNA. The
      goal of these studies was to determine which bases are pyridyloxobutylated to
      form AGT-reactive adducts. The model pyridyloxobutylating agent, 4
      [(acetoxymethyl)nitrosamino]-1-(3-pyridyl)-1-butanone (NNKOAc), was reacted with
      either poly(dAdT) or poly(dGdC) to generate DNA substrates for reaction with AGT.
      Only the pyridyloxobutylated poly(dGdC) was able to prevent the ability of
      partially purified rat liver AGT to repair O6-mG. These results paralleled those
      obtained for the corresponding methylated substrates. These studies are
      consistent with the pyridyloxobutylation of GC base pairs and not AT base pairs
      in the DNA to generate a substrate for AGT. In order to distinguish between the
      formation of reactive adducts at C residues versus G residues, two oligomers were
      designed that were complementary to one another. One oligomer contained A, T, and
      G residues, whereas its complement contained T, A, and C residues. Only the dG
      containing oligomer reacted with NNKOAc to generate an AGT-reactive adduct, again
      paralleling the results obtained for a methylating agent. These results
      demonstrate that pyridyloxobutylation of only guanine residues produces adducts
      that react with AGT. These AGT-reactive guanine adducts are relatively stable
      within DNA, with a half-life of 1-2 weeks at 37 degrees C. They represent up to
      70% of the total HPB-releasing adducts in the NNKOAc-treated DNA. We postulate
      that a potential AGT-reactive adduct is an O6-(pyridyloxobutyl)guanine adduct.

PMID- 8870982
TI  - Radical-initiated lipid peroxidation in low density lipoproteins: insights
      obtained from kinetic modeling.
AB  - We present kinetic models of various complexity for radical-initiated lipid
      peroxidation in low density lipoproteins (LDL). The models, comprised of
      simultaneous differential equations programmed in Mathematica, were used to
      evaluate the concentration profiles of the reactants of interest. Single-phase
      reaction schemes describing lipid peroxidation and antioxidation according to the
      "conventional" and tocopherol-mediated peroxidation (TMP) model were simulated
      for conditions of low and high radical fluxes produced by thermolabile azo
      initiators. The results show that the particular dependencies of the rates of
      lipid peroxidation (Rp) on the rates of initiation (Ri) for the two reaction
      schemes were accurately predicted by the simulations. Both models qualitatively
      predicted inhibition of lipid peroxidation in the presence of alpha-tocopherol
      (alpha-TOH) under high radical flux conditions, suggesting that both can describe
      inhibited lipid peroxidation in solution under these conditions. TMP, but not the
      conventional model, could also predict the experimentally observed complex
      behavior of LDL lipid peroxidation induced with different concentrations of azo
      initiators. Specifically, TMP faithfully reproduced the observed kinetic chain
      length of lipid peroxidation of > > 1 at low and < < 1 at high concentration of
      the initiator (i.e., 0.2 and 10 mM, respectively for LDL at 1 mumol apoB-100/L)
      during the alpha-TOH-containing period of oxidation. It also demonstrated the
      experimentally observed nondependence of RpTMP on Ri. Kinetic analysis of radical
      generation and initiation of lipid peroxidation in an extended, two-compartment
      model of TMP showed that phase separation of bimolecular reactions in a
      suspension of LDL particles can lead to a approximately 400-fold increase in the
      rate of lipid hydroperoxide formation. The experimentally observed co-antioxidant
      action of water-soluble ascorbate and lipid-soluble ubiquinol-10 were verified
      using this model. A simple biophysical model constituting the reactions of TMP
      and incorporating the compartmental nature of an LDL suspension is proposed.
      Together, the results demonstrate that TMP is the only model that fits the
      experimental data describing the early stages of LDL lipid peroxidation under
      various oxidizing conditions. The implications of our findings are discussed in
      relation to atherogenesis and a recently proposed alternative model of LDL lipid
      peroxidation (Abuja and Esterbauer (1995) Chem. Res. Toxicol. 8, 753).

PMID- 8870984
TI  - Substituted 2-hydroxy-1,2-dihydropyrrol-3-ones: fluorescent markers pertaining to
      oxidative stress and aging.
AB  - Previous observations that the aging process correlates with occurrence of
      certain fluorescent biological pigments have led to numerous efforts in
      elucidating the chemical nature of the fluorophores generated through reactions
      of primary amines and various products of lipid peroxidation. In this study,
      model reactions of saturated aldehydes with aliphatic amines in the presence of
      peroxides were found to generate structurally unusual fluorescent compounds.
      Substitution of a lysine-containing peptide for simpler amines has also yielded
      similar fluorescence. The spectral excitation and emission maxima (around 360 and
      430 nm, respectively) of these fluorophores match those widely reported in
      peroxidized biological objects. The fluorescent compounds in our model studies
      have been chromatographically isolated and their structures determined through
      mass spectrometry, NMR spectrometry, and Fourier-transform infrared spectroscopy.
      The spectrometric data indicate the fluorescent products to be alkylated 2
      hydroxy-1,2-dihydropyrrol-3-ones, obtained by the action of 1,2,4-triketone
      intermediates upon the primary amines. Independent syntheses of several 1,2,4
      triketones were carried out. One such triketone reacted with hexylamine to form a
      fluorescent compound spectroscopically identical to the fluorescent reaction
      product of hexanal, hydrogen peroxide, and hexylamine.

PMID- 8870983
TI  - Meso-2,3-dimercaptosuccinic acid mono-N-alkylamides: syntheses and biological
      activity as novel in vivo cadmium mobilizing agents.
AB  - Three meso-2,3-dimercaptosuccinic acid mono-N-alkylamides (meso-RNHCOCH(SH)CH(SH)
      COOH, where R = CHMe2, Mi-PDMA; CH2CHMe2, Mi-BDMA; and CH2CH2CHMe2, Mi-ADMA),
      were prepared via a synthetic route using the sulfhydryl-protected anhydride. 2,2
      Dimethyl-1,3-dithiolane-4,5-cis-dicarboxylic acid anhydride was opened up with 1
      mol of corresponding amine to give the SH-protected monoamide. Subsequent
      deblocking of the vicinal dithiol functionality was accomplished by conversion of
      the dithiolane into the mercury complex followed by reaction with H2S to give the
      target molecule. The potential utility of these compounds in chronic cadmium
      intoxication was examined by evaluation of their cadmium mobilizing efficacy in
      vivo in cadmium-loaded female albino rats using sodium N-benzyl-D-glucamine-N
      carbodithioate (BGDTC) as the standard drug. Compared to BGDTC, the new compounds
      were, except at the highest dosage studied, equally or more effective in
      decreasing retention of hepatic cadmium, while mostly less effective in
      decreasing renal cadmium. The greatest reductions were obtained with Mi-BDMS at 4
      x 1.5 mmol/kg, where liver and kidney cadmium levels were reduced to 12% and 59%
      of control levels, while at the same dosage BGDTC induced a reduction to 50% and
      13% of control levels. The order of the efficacy of the monoamides as hepatic
      cadmium mobilizing agents was found to be Mi-PDMA > Mi-BDMA > Mi-ADMA. However,
      the isopropyl analog, though very effective at reducing hepatic cadmium at a low
      dosage, was found to be more toxic than the isobutyl and isoamyl monoamides.
      While the new compounds were shown to be effective cadmium mobilizing agents, the
      specific compounds examined did not possess optimized structures in terms of the
      balance between effectiveness and toxicity.

PMID- 8870985
TI  - Intrachromosomal probes for mutagenesis by alkylated DNA bases replicated in
      mammalian cells: a comparison of the mutagenicities of O4-methylthymine and O6
      methylguanine in cells with different DNA repair backgrounds.
AB  - A shuttle vector was constructed in which a single O4-methylthymine (O4MeThy) or
      O6-methylguanine (O6MeGua) was positioned within a unique NheI restriction site.
      These lesions are among the many produced when alkylating agents interact with
      DNA and are the two most widely believed to account for the mutagenicity that
      follows the alkylation event. The shuttle vectors were transfected in parallel
      into Chinese hamster ovary cells that were either proficient (mex+) or deficient
      (mex-) in an endogenous alkyltransferase protein. The vectors integrated into the
      genome of the host, and the lesions were replicated along with the host
      chromosome. A portion of the integrated vector encompassing the originally
      adducted site was subsequently amplified by the polymerase chain reaction from
      the host genome to mediate analysis of mutation frequency and type. O4MeThy
      induced a high mutation frequency in both mex- and mex+ cells (28-50% in mex- and
      22-42% in mex+). O6MeGua induced a significant but lower level of mutagenesis in
      the repair-deficient (mex-) cells (7-8.5%) and was not detectably mutagenic in
      mex+ cells. Mutations induced by the methylated thymine in both cell types were T
      ->C transitions; the guanine adduct in mex- cells induced G-->A transitions.
      These results indicate that the O4MeThy lesion is more highly mutagenic than
      O6MeGua in the same genetic background, and that the former adduct, unlike the
      latter, does not appear to be repaired to a significant extent by the
      alkyltransferase or any other mammalian repair enzyme.

PMID- 8870986
TI  - Kinetics of S-nitrosation of thiols in nitric oxide solutions.
AB  - The S-nitroso adducts of nitric oxide (NO) may serve as carriers of NO and play a
      role in cell signaling and/or cytotoxicity. A quantitative understanding of the
      kinetics of S-nitrosothiol formation in solutions containing NO and O2 is
      important for understanding these roles of S-nitroso compounds in vivo. Rates of
      S-nitrosation in aqueous solutions were investigated for three thiols:
      glutathione, N-acetylcysteine, and N-acetylpenicillamine. Nitrous anhydride
      (N2O3), an intermediate in the formation of nitrite from NO and O2, is the most
      likely NO donor for N-nitrosation of amines as well as for S-nitrosation of
      thiols, at physiological pH. This motivated the use of a competitive kinetics
      approach, in which the rates of thiol nitrosation were compared with that of a
      secondary amine, morpholine. The kinetic studies were carried out with known
      amounts of NO and O2 in solutions containing one thiol (400 microM) and
      morpholine (200-5700 microM) in 0.01 M phosphate buffer at pH 7.4 and 23 degrees
      C. It was found that disulfide formation, transnitrosation reactions, and
      decomposition of the S-nitrosothiols was expressed as k7[N2O3][RSH], where RSH
      represents the thiol. The rate constant for S-nitrosation relative to that for
      N2O3 hydrolysis (k4) was found to be k7/k4 = (4.15 +/- 0.28) x 10(4), (2.11 +/-
      0.11) x 10(4), and (0.48 +/- 0.04) x 10(4) M-1 for glutathione, N-acetylcysteine,
      and N-acetylpenicillamine, respectively. The overall (observed) rates of
      nitrosothiol formation reflect the fact that [N2O3] varies [NO]2[O2] and that
      [N2O3] also depends on [RSH] and the concentration of phosphate. Using a detailed
      kinetic model to account for these effects, the present results could be
      reconciled with apparently dissimilar findings reported previously by others.

PMID- 8870987
TI  - 1,2,5,6-Diepoxyhexane and 1,2,7,8-diepoxyoctane cross-link duplex DNA at 5'-GNC
      sequences.
AB  - The carcinogenicity of epoxide compounds has been attributed to covalent binding
      to DNA. Whereas monoepoxides form only monoadducts, diepoxides can form both
      monoadducts and interstrand cross-links. The latter are believed to be the more
      significant cytotoxic lesions as diepoxides are frequently more carcinogenic and
      mutagenic than their monoepoxide analogues. We therefore examined the relative
      DNA interstrand cross-linking capabilities of several diepoxides with respect to
      chain length, molecular flexibility, reported carcinogenic potential, and DNA
      sequences targeted. Using denaturing polyacrylamide gel electrophoresis, we found
      that 1,2,5,6-diepoxyhexane and 1,2,7,8-diepoxyoctane share the 5'-GNC target
      sequence previously found for 1,2,3,4-diepoxybutane [Millard, J.T., and White,
      M.M. (1993) Biochemistry 32, 2120-2124] and that the efficiency of cross-linking
      this sequence may reflect carcinogenicity, 1,2,5,6-Diepoxycyclooctane, the
      biologically inactive rigid analogue of 1,2,5,6-diepoxyhexane, was found to be a
      poor cross-linker of all DNA sequences examined. Moreover, increasing the
      diepoxyalkane chain length did not result in enhanced cross-linking ability.

PMID- 8870988
TI  - Products of aniline and triglycerides in oil samples associated with the toxic
      oil syndrome.
AB  - The toxic oil syndrome (TOS) was a devastating disease that occurred in Spain in
      1981. The disease was associated with the consumption of aniline-denatured and
      refined rapeseed oil that had been illegally sold as olive oil. Many aniline
      derived oil components have been identified in the oils; however, no etiological
      agent has ever been identified for this disease. We have continued the study of
      the TOS problem by applying new technology in the form of liquid chromatography
      interfaced via atmospheric pressure ionization with tandem mass spectrometry.
      Using liquid chromatography tandem mass spectrometry, we studied diluted TOS
      associated oils by direct analysis without prior sample treatment. Using this
      technology, we found new classes of compounds that are associated with disease
      related oils. The compounds that have been identified are esters and ester amides
      of 3-(N-phenylamino)-1,2-propanediol and are products of aniline and
      triglycerides. Because of the varied fatty acid (oleic acid, etc.) content of the
      oils, many variations of the above compounds are possible. We now report the
      identities of more than 20 compounds not previously identified. These compounds
      are strongly associated with oils that caused the toxic oil syndrome. We believe
      these compounds should be considered for future animal studies.

PMID- 8870990
TI  - Synthesis and monoamine oxidase B catalyzed oxidation of C-4 heteroaromatic
      substituted 1,2,3,6-tetrahydropyridine derivatives.
AB  - The monoamine oxidase B (MAO-B) catalyzed oxidation of amines has been proposed
      to proceed via a polar pathway, an initial single-electron transfer pathway and
      an initial hydrogen atom transfer pathway. Results from previous studies on
      selected N-cyclopropyl-4-substituted-1,2,3,6-tetrahydropyridine derivatives have
      led us to consider a mechanism for these cyclic tertiary allylamines which may
      not necessarily involve the aminyl radical cation as required by an initial
      single-electron transfer step. The studies summarized in this paper were
      undertaken to explore further the structural features that determine the MAO-B
      substrate and/or inactivator properties of various 1,4-disubstituted
      tetrahydropyridine derivatives. We report here the results of our studies on the
      synthesis and MAO-B catalyzed oxidation of 1-methyl- and 1-cyclopropyl-1,2,3,6
      tetrahydropyridine derivatives bearing a variety of heteroaromatic groups at C-4.
      All of the N-cyclopropyltetrahydropyridine analogs were time and concentration
      dependent inhibitors of MAO-B while all of the N-methyltetrahydropyridine analogs
      and the N-cyclopropyl-4-(1-methyl-2-pyrryl)tetrahydropyridine analog were
      substrates. The substrate properties (Kcat/KM) covered a range of 6 to 1800 min-1
      mM-1 while the range for the inactivator properties for which Kinact/KI values
      could be obtained was 0.1-1.0 min-1 mM-1. The partition ratios for the N
      cyclopropyl analogs varied from 4 to 17 except for the 4-(1-methyl-2-pyrryl)
      analog, which had a partition ratio of 400. These results are discussed in terms
      of the putative allylic radical intermediate and in the context of the hydrogen
      atom transfer and single-electron transfer based mechanisms.

PMID- 8870989
TI  - In vitro studies on the metabolic activation of the furanopyridine L-754,394, a
      highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4.
AB  - L-754,394, a furanopyridine derivative, is an experimental anti-HIV agent which
      has been shown to be an unusually potent and selective inhibitor of cytochrome
      P450 3A enzymes in a number of mammalian species. In the present studies, L
      754,394 was demonstrated to undergo NADPH-dependent metabolic activation in
      hepatic microsomal preparations from rats, dogs, rhesus monkeys, and humans to
      electrophilic intermediates which became bound covalently to cellular proteins.
      The extent of binding was species-dependent, the highest levels being observed
      with liver microsomes from rhesus monkeys. Inclusion in incubation media of the
      nucleophilic trapping agents glutathione, cysteine, or methoxyamine led to a
      modest (15-25%) decrease in the covalent binding, while trichloropropylene oxide,
      an inhibitor of epoxide hydrolase, had no effect. When L-754,394 was incubated
      with monkey liver microsomes, the corresponding dihydrofurandiol was identified
      as a metabolite by liquid chromatography-tandem mass spectrometry. In contrast,
      when incubations were carried out in the presence of methoxyamine, the O
      methyloxime derivative of the ring-opened dihydrodiol tautomer was formed, while
      inclusion of glutathione or N-acetylcysteine led to the formation of S-linked
      conjugates of a putative furan epoxide. Collectively, these results are taken to
      indicate that L-754,394 undergoes cytochrome P450-dependent oxidation of the
      fused furan ring system, leading to the formation of chemically-reactive
      intermediates. One or more of these electrophilic species may be responsible for
      the autocatalytic destruction of cytochrome P450 enzymes which accompanies L
      754,394 metabolism in vitro and in vivo.

PMID- 8870991
TI  - Inhibitory and noninhibitory monoclonal antibodies to human cytochrome P450 2E1.
AB  - A panel of 17 hybridomas producing (MAbs) against human cytochrome P450 2E1
      (h2E1) was generated by immunizing mice with baculovirus-expressed h2E1. All 17
      hybridoma clones gave positive ELISA or immunoblots with either baculovirus-or
      vaccinia virus-expressed h2E1. Two of the latter were further developed due to
      their desirable characteristics. MAb 1-73-18 was found to be a powerful inhibitor
      of P450 h2E1; however, it did not yield a positive immunoblot. MAb 2-106-12 was
      found to be noninhibitory but formed a strong positive immunoblot with P450 h2E1.
      These MAbs to h2E1 were highly specific and did not recognize six other human
      P450s as tested with ELISA or immunoblot analyses. The MAbs to baculovirus
      expressed h2E1 also reacted with h2E1 expressed from a vaccinia virus vector
      system as well as with microsomal fractions of human and acetone-treated rat
      liver. MAb 1-73-18 inhibited h2E1 enzyme activity catalyzing the metabolism of
      phenanthrene by 85%, p-nitroanisole by 90%, 4-methylanisole by 60-80%, toluene by
      90%, and chlorzoxazone by 90%. The inhibitory MAb 1-73-18 is uniquely useful for
      determining the contribution of h2E1 to the metabolism of h2E1 substrates in
      human liver containing multiple P450s. The quantitatively determined contribution
      of h2E1 to the metabolism of the above substrates ranged from 25% to 75%. Thus,
      h2E1 was responsible for the following percentages of the total metabolism in
      human liver: p-nitroanisole (35%), phenanthrene (23%), methylanisole to cresol
      (25%), methylanisole to methoxybenzyl alcohol (12%), toluene (40%), and
      chlorzoxazone (72%). The MAb 2-106-12 forming a strong immunoblot is useful for
      determining the amount of h2E1 protein in a tissue. Thus the utility of the
      inhibitory and immunoblot positive MAbs is complementary and can determine both
      the contribution of h2E1 to the metabolism of specific substrates and the amount
      of h2E1 protein in human tissue. The analyses of metabolism with the inhibitory
      MAb 1-73-18 can be generalized and applicable to all h2E1 substrates.

PMID- 8870992
TI  - d-Amphetamine interaction with glutathione in freshly isolated rat hepatocytes.
AB  - Hepatocellular damage has been reported as a consequence of amphetamine intake
      for which little is known about the respective biological mechanisms involved. To
      give a better insight of cellular d-amphetamine effects, the present study was
      performed to evaluate d-amphetamine effects on glutathione homeostasis, in vitro,
      using freshly isolated rat hepatocytes. Cell viability and lipid peroxidation
      were also evaluated. Incubation of freshly isolated rat hepatocytes with d
      amphetamine (0.08, 0.20, 0.40, and 2.00 mM) induced a concentration dependent
      glutathione depletion which was observed at all times (1, 2, and 3 h of
      incubation). After 3 h of incubation, cellular GSH decreased to 85%, 78%, 71% and
      47% of control levels for the referred concentrations, respectively. At the third
      hour of incubation, GSSG levels were only slightly increased for the three higher
      concentrations of d-amphetamine. The mass spectral study of the methanolic
      supernatants obtained from hepatocytes incubated with all d-amphetamine
      concentrations revealed the presence of the p-hydroxyamphetamine glutathione
      adduct (glutathion-S-yl)-p-hydroxyamphetamine. Pretreatment of hepatocytes with
      the P450 inhibitors metyrapone (1 mM) and iprindole (10 microM) significantly
      prevented the glutathione depletion induced by d-amphetamine. This inhibition was
      more effective for iprindole than for metyrapone. Incubation of isolated
      hepatocytes with p-hydroxyamphetamine (0.10 mM) for 3 h did not result in any
      modification of cell viability or GSH or GSSG levels. Also, in the mass spectrum
      study performed on these samples, the characteristic adduct obtained for d
      amphetamine incubations was not detected. The above data suggest that the
      observed glutathione depletion induced by d-amphetamine is at least in part due
      to the conversion of d-amphetamine into (glutathion-S-yl)-p-hydroxyamphetamine
      and that P450 2D seems to have an important role in this metabolism. In spite of
      the results obtained, showing glutathione homeostasis alterations, incubation of
      freshly isolated rat hepatocytes with d-amphetamine did not result in any
      modification of cell viability or lipid redox status.

PMID- 8870993
TI  - Production of a high-affinity monoclonal antibody specific for 7
      (benzo[alpha]pyren-6-yl) guanine and its application in a competitive enzyme
      linked immunosorbent assay.
AB  - Molecular dosimetry of depurinating DNA adducts of benzo[alpha]pyrene (BP) is a
      promising new approach to measurement of cancer risk associated with exposure to
      polycyclic aromatic hydrocarbons (PAH). Depurinating adducts of BP are
      spontaneously released from DNA and can be detected in urine. As a first step
      toward developing a monoclonal antibody (MAb)-based molecular dosimetry for
      depurinating DNA adducts of BP, a MAb (MAb CB53) has been produced with high
      specific affinity for 7-(benzo[alpha]pyren-6-yl)guanine (BP-6-N7Gua), a major
      depurinating adduct of BP. Production of this MAb was dependent on the successful
      synthesis of an effective immunogen consisting of the hydrophobic BP-6-N7Gua
      coupled to carrier protein via a rigid spacer arm. A competitive enzyme-linked
      immunosorbent assay (ELISA) for BP-6-N7Gua has been developed with MAb CB53 and
      has been applied to evaluation of MAb binding and to quantitation of BP-6-N7Gua
      in a biological sample. The MAb binds with high affinity to BP-6-N7Gua (Ka = 1.4
      x 10(8) M-1) and to BP-6-N7Ade (Ka = 0.7 x 10(8) M-1), another major depurinating
      DNA adduct of BP, but discriminates well between BP and BP-6-N7Gua. BP-6-N7Gua
      produces 50% inhibition at 750 fmol in the competitive ELISA, whereas BP produces
      50% inhibition at 960 000 fmol. Binding affinities to selected PAH, BP-DNA
      adducts, and BP metabolites indicate significant contributions of the hydrophobic
      region C-3, C-4, and C-5 of BP and the polar oxygen of guanine to MAb/adduct
      binding. In a preliminary test of the utility of the competitive ELISA for
      quantitation of BP-6-N7Gua in urine samples, the assay (sensitivity: 200 fmol per
      well) produced an accurate determination of the adduct added to normal human
      urine.

PMID- 8870994
TI  - Cross-linking of human placenta pi class glutathione S-transferase dimer by
      chlorambucil.
AB  - Interaction of chlorambucil and the glutathione-depleted human placenta pi class
      glutathione S-transferase (pi GST) results in the formation of a complex between
      the drug and the protein at physiological pH. This complex is not formed in the
      presence of glutathione or S-hexylglutathione. Molecular mass measurement of the
      reaction product using matrix-assisted laser desorption mass spectrometry
      indicates that one molecule of chlorambucil cross-links two subunits of the
      homodimeric protein. A combination of enzymic proteolysis, high performance
      liquid chromatography, and mass spectrometry reveals that chlorambucil alkylation
      occurs at cysteine 47 of one subunit and cysteine 101 of the second subunit. This
      result supports the idea that conformational changes occur in glutathione
      depleted pi GST, which allow the bifunctional tether of chlorambucil to cross
      link the two subunits of the protein.

PMID- 8870995
TI  - 32-P-HPLC analysis of DNA adducts formed in vitro and in vivo by 2-amino-1-methyl
      6-phenylimidazo[4,5-b]pyridine and 2-amino-3,4,8-trimethyl-3H-imidazo[4,5
      f]quinoxaline, utilizing an improved adduct enrichment procedure.
AB  - DNA adducts of 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino
      3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-diMeIQx), synthesized in vitro
      with calf thymus DNA and formed in vivo in the male Wistar rat, were enriched
      from digested DNA by butanol extraction before 32P-postlabeling. The recovery
      after butanol enrichment was 79% and 32% for in vitro modified PhIP- and 4,8
      diMeIQx-DNA adducts, respectively. Crude postlabeling mixtures were
      chromatographically separated by high-performance liquid chromatography with on
      line 32P-detection (32P-HPLC). The major PhIP- and 4,8-diMeIQx-DNA adducts formed
      in vitro cochromatographed with the respective pdGp-C8 adduct standard. 32P-HPLC
      was also used to separate hydrolysates of in vitro formed PhIP-DNA and 4,8
      diMeIQx-DNA that had been 32P-postlabeled under ATP-deficient conditions. The
      adduct recovery of the ATP-deficient method relative to the improved butanol
      enrichment procedure was 29% and 59% for total PhIP-DNA and 4,8-diMeIQx-DNA
      adducts, respectively. Simplified DNA adduct patterns were obtained when the
      postlabeling mixtures were incubated with nuclease P1, suggesting incomplete DNA
      hydrolysis. After nuclease P1 treatment, the major DNA adducts of PhIP and 4,8
      diMeIQx formed in vitro cochromatographed with the respective pdG-C8 adduct
      standard. In vivo PhIP formed what appeared to be multiple DNA adducts; however,
      after nuclease P1 treatment the PhIP-associated peaks were concentrated into a
      single peak cochromatographing with pdG-C8-PhIP, 4,8-diMeIQx formed multiple DNA
      adducts in vivo. Nuclease P1 treatment resulted in two 4,8-diMeIQx related peaks,
      one cochromatographing with pdG-C8-4,8-diMeIQx. The second peak remains
      unidentified. The improved workup procedures in combination with the high
      resolution and reproducibility of the 32P-HPLC system should be useful for
      characterization of PhIP- and 4,8-diMeIQx-DNA adducts in DNA modified by complex
      mixtures.

PMID- 8870996
TI  - Peripheral blood stem cell transplantation in common solid tumours: passing phase
      or new era?

PMID- 8870997
TI  - Randomized clinical trials are the best form of medical audit.

PMID- 8870998
TI  - The CD34 antigen: potential clinical advantages of CD34 selection.
AB  - The availability of monoclonal antibodies directed towards the haemopoietic cell
      surface antigen CD34 has facilitated accurate measurement, by flow cytometry, of
      CD34 positive cell frequencies in bone marrow and peripheral blood. In addition,
      a range of CD34 selection techniques, to purify peripheral blood progenitor cells
      or bone marrow prior to transplantation, have been developed. CD34 positive stem
      and progenitor cells may be selected with final purities in excess of 90%. Such
      pure populations of CD34 positive stem cells may be useful in several clinical
      areas, including tumour cell purging and T-cell depletion, and as a basis for
      gene therapy and stem cell expansion.

PMID- 8870999
TI  - Prophylactic mastectomy for genetic predisposition to breast cancer: the
      proband's story.
AB  - The identification of the BRCA1 gene may prove a mixed blessing in the short
      term. First, the demand for testing might outstrip available resources, the
      ethics of testing are complex and the advice to give someone who tests positive
      is as yet unclear. Furthermore, the psychological dynamics within such families
      have not yet been considered seriously. As these families might be widespread,
      there will inevitably be problems involving clinical genetic centres in different
      parts of the country, or for that matter, in different areas of the world. In
      this paper we provide a case report, which might be considered an adumbration of
      things to come. The proband in this story (a co-author) was known to have
      inherited a genetic predisposition to cancer. This was because her identical twin
      had already developed the disease and she came from a kindred with a very high
      probability for carrying a dominant breast cancer gene in the germ line. We
      describe the personal reactions of an individual woman faced with these difficult
      decisions, the impact on her family and the impact on the clinical genetic
      services in different parts of the country. Our experience could help to provide
      a template for the development of regional services once genetic testing for
      predisposition to breast cancer becomes widely available.

PMID- 8871000
TI  - Factors affecting acute skin toxicity in patients having breast irradiation after
      conservative surgery: a prospective study of treatment practice at the Royal
      Marsden Hospital.
AB  - The results are presented of a prospective study of acute skin toxicity in 197
      patients with early stage breast cancer, who were treated by conservative surgery
      and postoperative radiotherapy. We have examined the factors determining the
      severity of the acute skin reaction with particular reference to the degree of
      dry or moist desquamation at the completion of treatment. One hundred and ten
      patients had treatment with radiotherapy alone. The remaining 87 received
      synchronous chemotherapy with breast irradiation, using either the 3M or the 2M
      regimen, consisting of mitoxantrone and methotrexate, with (3M) or without
      Mitomycin-C (2M). Patients were analysed according to both the severity and the
      site of the skin reaction, age, dose, dose variation across the central outline,
      treatment technique, beam energy, field separation and breast size. A univariate
      analysis of these results, which has been presented as an odds ratio of the
      likelihood of developing a moderate or severe reaction in comparison with those
      scored as mild, has shown that several factors are associated with an increase in
      the acute skin reaction. These include the use of the semi-supine technique (odds
      ratio (OR) = 7.3 (95% CI 3.7-14.6)), beam energy (60Co: 6-10 MV photons OR = 5.9
      (95% CI 2.6-13.4)), field separation (> or = 20 cm: < 20 cm OR = 4.1 (95% CI 2.2
      7.8)), dose variation across the central outline (> or = 10%: < 10% OR = 9.7 (95%
      CI 2.6-36.4)), inclusion of the axilla (OR = 4.6 (95% CI 2.4-8.9)), and bust size
      (bra cup size C and D: A and B OR = 4.6 (95% CI 2.7-11.9)). Using multivariate
      logistic regression, the technique of radiation delivery and bust size were shown
      to be independently significant variables affecting acute skin reaction. In view
      of the high correlation between variables (e.g. radiotherapy technique and beam
      energy) it is still not possible to specify with definite certainty which is the
      primary variable causing the skin reaction. However 20/57 (35%) of patients
      treated by the semisupine technique sustained a severe skin reaction, with > 10%
      dry or moist desquamation in the treatment field. This compares with only 6/140
      (4%) patients treated by the supine method. A possible mechanism by which
      treatment using the semisupine technique may enhance acute toxicity is discussed.
      We conclude that there are both treatment and patient related factors that will
      increase the acute skin reaction after breast irradiation.

PMID- 8871001
TI  - An acute toxicity study on the effects of synchronous chemotherapy and
      radiotherapy in early stage breast cancer after conservative surgery.
AB  - One hundred and ninety-seven patients with early stage breast cancer, who were
      treated initially with conservative surgery, were evaluated prospectively for
      acute toxicity after completing post-operative irradiation. Eighty-seven of these
      patients had synchronous chemotherapy with the 3M regimen (mitoxantrone,
      methotrexate and Mitomycin-C) during radiotherapy. The results indicate that
      patients receiving chemotherapy and radiotherapy (CRT) showed no significant
      difference in acute skin toxicity (AST) when compared with those treated with
      radiotherapy alone (RTO), with an odds ratio (OR = 0.6) and 95% confidence
      intervals (0.3-1.1) of developing either a moderate or severe, compared with a
      mild, skin reaction. Even after controlling for other confounding factors, such
      as treatment technique and beam energy, patients treated with the supine
      technique using 6-10 MV photons still displayed no significant difference in AST,
      with 12/74 (16%) patients in the CRT group and 14/66 (21%) in the RTO group
      developing a moderate or severe skin reaction (OR = 0.7 (95% CI 0.3-1.7)). Four
      of the 87 patients treated with CRT developed symptomatic acute radiation
      pneumonitis, three of whom were found to have > 3 cm of lung length on their
      simulator or check films. The volume of lung included within the treatment field
      was found to be statistically significant (P = 0.005) in predicting the onset of
      radiation pneumonitis in the CRT group. None of these patients has suffered any
      symptomatic late lung toxicity. We conclude that synchronous chemotherapy and
      radiotherapy, when using the 3M regimen, is feasible for patients having adjuvant
      treatment for early stage breast carcinoma and there is no significant increase
      in AST. However, it is associated with an increase in acute radiation pneumonitis
      when a significant volume of lung is included within the radiation treatment
      field.

PMID- 8871002
TI  - Long-term survival and symptom palliation in small primary bronchial carcinomas
      following treatment with intraluminal radiotherapy alone.
AB  - Between April 1988 and December 1992, 37 patients with small, previously
      unirradiated, primary non-small cell carcinomas of the bronchus causing symptoms
      due to endobronchial disease were treated at the Christie Hospital, Manchester,
      with a single fraction of high dose rate intraluminal radiotherapy (ILT) using
      the microSelectron-HDR machine. Small primary (SP) lesions were defined as being
      less than 2 cm in diameter in a direction perpendicular to the central axis of
      the iridium-192 treatment source. Fifteen patients (41%) were treated to a dose
      of 15 Gy and 22 patients (59%) to 20 Gy at a distance of 1 cm from the central
      axis of the source. At 6 weeks following ILT, improvement in symptoms was seen in
      the following percentages of patients: haemoptysis 96%, pulmonary collapse 69%,
      cough 55% and dyspnoea 52%. The magnitude of improvement in these symptoms was
      largely maintained in patients surviving to 4 months and then 12 months post-ILT.
      Median actuarial survival was 709 days, 2-year survival 49.4% and 5-year survival
      14.1%. Overall, there was no significant difference in survival after treatment
      with 20 Gy compared with 15 Gy at 1 cm. At the close of study, there were four
      patients still alive without disease recurrence with survivals of 38, 48, 49 and
      63 months. All had had biopsy-proven squamous cell carcinomas and all had been
      treated with 20 Gy at 1 cm. Five patients died from massive haemoptysis as a
      terminal event at 4, 9, 9, 10 and 11 months post-ILT, well below the median
      survival for this group of patients. Again, all had been treated with 20 Gy as
      opposed to 15 Gy at 1 cm. Over the same time period, 287 patients with non-small
      cell carcinomas of more than 2 cm in diameter (large primary lesions, LP), were
      treated with a single fraction of ILT only, as their initial treatment. A
      consistently greater percentage of patients with SP lesions showed an improvement
      in the symptoms of haemoptysis and pulmonary collapse when compared with patients
      with LP lesions. Patients with LP lesions demonstrated a decreased actuarial
      survival when compared with SP lesions, with median survival being 156 days, 2
      year survival 3.1% and no survivors beyond 39 months. This study demonstrates
      that, in patients with small endobronchial carcinomas a single fraction of ILT
      can give efficient palliation of symptoms and lead to long term disease-free
      survival, but that a dose of 20 Gy may be at the limit of bronchial radiation
      tolerance for a single dose technique employing a high dose rate source.

PMID- 8871003
TI  - Successful thrombolysis of SVC thrombosis associated with Hickman lines and
      continuous infusion chemotherapy.
AB  - In a pilot study of continuous infusion 5-fluorouracil and intermittent bolus
      doxorubicin and cyclophosphamide in women with breast cancer, four of 24 patients
      developed symptomatic superior vena cava or innominate vein thrombosis associated
      with the Hickman line, despite prophylactic treatment with very low dose warfarin
      (1-3 mg/day). In all four patients, local thrombolysis with streptokinase was
      successful and chemotherapy was continued through the Hickman line under
      anticoagulant cover, maintaining an international normalized ratio of 2.0-3.0. No
      patient developed recurrent thrombosis. Prophylactic anticoagulation should be
      considered in patients receiving continuous infusion chemotherapy through Hickman
      lines, as they are at risk of proximal vein thrombosis. A randomized study is
      needed to address the question of the optimum anticoagulant regimen to prevent
      such thromboses.

PMID- 8871004
TI  - Artificial radiation menopause: where are the ovaries?
AB  - For ovarian ablation using radiotherapy, the pelvis is irradiated using generous
      fields sizes, as the position of the ovaries is uncertain. To assess the
      variation in ovarian position, we reviewed 81 sequential CT examinations of the
      pelvis performed in women under the age of 50 years. Women with pelvic malignancy
      or previous pelvic surgery were excluded from the analysis, leaving 30 eligible
      women. One or both ovaries could be clearly identified in 23 of these patients;
      in 19 (83%), the ovaries were located within the upper two-thirds of a ring
      defined by the sacroiliac joints, the bony side wall of the pelvis and the
      symphysis pubis. The ovaries were located outside this ring in four (17%) women.
      Ovarian position did not appear to be influenced by parity, uterine orientation,
      the degree of bladder filling or faecal loading within the rectum. The treatment
      volume for artificial radiation menopause has been variably defined; the upper
      part of the pelvis may not be included. The results from this retrospective study
      suggest that the treatment volume should extend from the inferior border of the
      fifth lumbar vertebra down to a level traversing the middle of the femoral heads
      and 1 cm lateral to the pelvic side walls.

PMID- 8871005
TI  - Irradiation of the scrotum: what some men need MOST: the Manual Orchid Shielding
      Technique.
AB  - Although the need for radiotherapy to the scrotum is now unusual, shielding for
      the contralateral testis is used to maintain fertility and to preserve the
      endocrine function of the testis. We report a simple radiotherapy technique to
      achieve this by manually removing the contralateral testis proximally from the
      scrotum, to the level of the inguinal ring, where it is held by the patient
      during radiotherapy. A lead shield placed over the hand, testis and penis reduces
      the dose to the testis to an acceptable < 1.5% of the tumour dose. This can be
      confirmed by thermoluminescent dosimetry.

PMID- 8871006
TI  - Malignant hypercalcaemia in pregnancy and antenatal administration of intravenous
      pamidronate.
AB  - A patient is reported who was found to have metastatic breast cancer in
      pregnancy. Intravenous pamidronate was given with beneficial effect in the third
      trimester. There were no serious adverse effects on the foetus.

PMID- 8871007
TI  - Gestational choriocarcinoma metastatic to the brain treated successfully by
      stereotactic radiosurgery and chemotherapy.
AB  - Metastatic gestational choriocarcinoma not uncommonly affects the central nervous
      system. If possible, the initial management of these metastases is surgical
      excision prior to chemotherapy, since these lesions are haemorrhagic. We report a
      patient with choriocarcinoma metastatic to the brain in whom surgery was
      potentially hazardous. Treatment was successfully given with stereotactic
      radiosurgery followed by chemotherapy.

PMID- 8871008
TI  - Medullary carcinoma of the thyroid misdiagnosed as differentiated thyroid
      carcinoma.
AB  - Four patients are presented, who were initially diagnosed and treated for
      differentiated thyroid carcinoma, but subsequently discovered to have medullary
      carcinoma. We suggest that tumour histopathology needs to be carefully reviewed
      in all cases of thyroid cancer, especially those having atypical clinical or
      pathological features. This should be completed prior to further therapeutic
      intervention, such as the administration of ablative radioactive iodine.

PMID- 8871009
TI  - Informed consent in oncology.

PMID- 8871010
TI  - Informed consent in oncology: do we need it?

PMID- 8871011
TI  - Differences in telangiectasia incidence between centres are not readily
      predicted.

PMID- 8871012
TI  - Number of mutans streptococci or lactobacilli in a total dental plaque sample
      does not explain the variation in caries better than the numbers in stimulated
      whole saliva.
AB  - For practical reasons the numbers of mutans streptococci (MS) and lactobacilli
      (LB) in plaque are commonly estimated from saliva samples. The saliva counts are
      considered to be a reasonable indicator of the entire dentition's total microbial
      load. However, the value of salivary counts for explaining and predicting caries
      have been found to be low. There was therefore reason to compare the
      relationships between caries on the one hand and, on the other, the number of MS
      or LB in plaque and in saliva, respectively, in order to assess their relative
      merits for explaining the variation in caries, both in a total material and in
      subgroups with less favourable oral hygiene. Sixty children aged 14-15 years
      participated in the study. Caries and plaque were registered and the number of MS
      and LB was estimated in total plaque and in stimulated saliva samples. The
      results showed that the number of MS or LB in plaque did not explain the
      variation in caries to a greater degree than did the salivary counts. For both
      bacteria the explanatory values increased, as expected, in subgroups with less
      favourable oral hygiene, but not even at this higher level of explanation was
      there any difference between plaque and saliva. The LB count was a stronger
      explanatory variable than the MS count. It was concluded that the number of MS
      and LB, estimated in total plaque as well as in saliva samples, is not a useful
      tool in prediction.

PMID- 8871013
TI  - Salivary mutans streptococci and dental caries patterns in pre-school children.
AB  - Recent studies have suggested that the identification of caries as discrete
      patterns may be valuable in describing and predicting caries experience on an
      individual basis. The purpose of this study was to assess the association between
      levels of salivary mutans streptococci and the prevalence, incidence and
      distribution of caries patterns in the primary dentition. A cohort of pre-school
      children (n = 146, mean age 3.8 yr) were examined for dental caries and sampled
      for salivary mutans streptococci (SMS) at baseline and once annually for 2 yr.
      Children's tooth surfaces were categorized into four patterns: pit/fissure,
      maxillary anterior, posterior proximal, and buccal/lingual smooth surface.
      Salivary mutans streptococci were enumerated using a tongue blade technique, and
      were categorized as low (0 CFU), moderate (1-50 CFU) and high (> 50 CFU). At year
      2, children with high baseline SMS had the 1) highest prevalence of caries (87%)
      and the highest dmfs (9.15); 2) highest prevalence of each pattern, and 3)
      greatest number of patterns. Among children with the pit/fissure pattern, those
      with high baseline SMS had the greatest pit/fissure dmfs after 2 yr. Results show
      that baseline SMS levels were associated with both cross-sectional and
      longitudinal caries experience, numbers of caries patterns, and the prevalence
      and severity of those patterns.

PMID- 8871014
TI  - Dental caries in relation to diet, saliva and cariogenic microorganisms in
      Tanzanians of selected age groups.
AB  - The relationship between diet and dental caries in a Tanzanian population was
      studied. Mutans streptococci, lactobacilli, yeasts, salivary flow rate as well as
      buffer effect were also analyzed. A random sample of 12-, 35-44- and 65- to 74-
      year olds was drawn from Msongola (rural) and Ukombozi (urban), Dar-es-Salaam.
      The mean of two 24-h recalls was used for the assessment of food intake. The
      percentage of those with at least one carious tooth ranged from 30% in the 12
      year-olds to 80% in the oldest age group. The mean number of decayed teeth (DT)
      increased significantly with age (P = 0.000) but was not significantly associated
      with the area of residence. DT increased significantly (P = 0.048) with the
      number of snacks per day and was also associated with dietary sucrose (P =
      0.025), total carbohydrates (P = 0.002) and fiber (P = 0.002). Among salivary
      variables lactobacilli (P = 0.000) correlated positively with DT. Our study did
      not reveal any strong association between total energy intake and dental caries
      in rural or urban populations in Tanzania but snacking and sucrose intake were
      significantly associated with caries, in particular in the urban area.

PMID- 8871015
TI  - A two-centre study to determine dentists' agreement with current guidelines on
      the frequency of bitewing radiography.
AB  - The main aim of this study was to compare the intervals between initial and
      recall bitewing radiography recommended by general dental practitioners (GDPs)
      with those advocated in published guidelines. A questionnaire containing eight
      clinical scenarios was distributed to GDPs in two areas of England, Birmingham
      (fluoridated) and Manchester (non-fluoridated). The response rate was 70.8%.
      There was considerable agreement (> 66.0%) with recommended guidelines for all
      low caries risk scenarios, but in three out of the four high caries risk
      scenarios a minority of dentists were in agreement (< 49.5%). In high caries risk
      scenarios there was a tendency to over prescription with adult patients and under
      prescription for patients in the mixed dentition. For all low risk scenarios
      except the youngest patient, there was a significantly greater agreement with the
      guidelines amongst Birmingham dentists, with the Manchester group having a
      greater tendency to over-prescription. This difference may be related to the
      effects of fluoridation of the water supply in the Birmingham area. There was
      generally greater agreement with the guidelines amongst younger dentists, with
      their older colleagues tending to under-prescription. The results suggest that
      greater emphasis on selection criteria in continuing education of dentists is
      required.

PMID- 8871016
TI  - Accuracy of dental hygienists in diagnosing dental decay.
AB  - During recent decades, the duties and care rendered by Swedish dental hygienists
      have continuously expanded, and since 1991 they are licensed to practice dental
      hygiene independently. The aim of the present study was to investigate the
      accuracy of dental hygienists in examining and recording dental caries in
      comparison with dentists performing identical examinations. The study included
      two parts: A) Registration of carious lesions from radiographs of 100 extracted
      teeth, where the correct diagnosis could be verified, and B) clinical examination
      and registration of carious lesions in 213 patients. No statistically significant
      differences could be found between the dental hygienists' and their control
      dentists' accuracy to diagnose and record dental decay, with the exception of the
      number of initial lesions (white spot lesions) registered clinically, where the
      dental hygienists recorded more buccal and lingual lesions. Irrespective of the
      group of examiners (dental hygienists or dentists), however, the inter-examiner
      variation was wide. The variation decreased with the size of the lesion and
      increased with the age of the patient. This study suggests that no patient with a
      restorative treatment need would have been neglected if the dental hygienists had
      performed the examination, and, possibly, a more accurate non-restorative
      treatment need would have been addressed.

PMID- 8871017
TI  - Dental health of aboriginal pre-school children in Brisbane, Australia.
AB  - This investigation studied the dental health status of a group of 184 Australian
      Aboriginal children with a mean age of 4.4 +/- 0.8 years, who were attending pre
      schools in metropolitan Brisbane, a non-fluoridated state capital city. The DDE
      (Developmental Defects of Enamel) Index was used to chart enamel hypoplasia and
      enamel opacities. WHO criteria was used to diagnose dental caries. The results
      showed that 98% of children had at least one tooth showing developmental enamel
      defects. Each child had a mean of 3.8 +/- 1.7 teeth affected by enamel hypoplasia
      and another 1.1 +/- 0.8 teeth affected by enamel opacity. Seventy-eight percent
      of the children had dental caries. The mean number of decayed, missing, filled
      teeth (dmft) per child was 3.8 +/- 3.7. The decayed component constituted 3.5
      (95%) of the mean dmft, indicating a high unmet restorative need in this group.
      The mean dmfs (decayed, missing, filled, surfaces) was 5.9 +/- 7.3. Maxillary
      anterior labial decay of at least one tooth affected 43 (23%) of the children. In
      this sub-group, the dmft and dmfs was 9.1 +/- 2.8 and 15.4 +/- 7.7 respectively.
      Oral debris was found in 98% of the children. It is hypothesized that the high
      levels of underlying developmental enamel defects, compounded by low fluoride
      exposure, poor oral hygiene and a diet high in refined sugars pose an important
      caries risk factor in this group of children.

PMID- 8871018
TI  - Equality in satisfaction, perceived need, and utilization of dental care in a 50
      year old Swedish population.
AB  - Satisfaction with dental care, perceived need for dental care, and dental care
      utilization were analyzed as to equality in geographical, socio-economic, and
      gender distributions. The study base was a cross-sectional mail questionnaire
      sent in 1992 to all 50-year old persons (totally 8890) in Orebro and Ostergotland
      counties in Sweden. Measures of the variables were all based on self-assessments.
      The response rate was 71.3%. The results showed no large inequalities as to
      satisfaction, except the aspect travel time for rural residents. They also had
      higher perceived need for dental care. For utilization of dental care, workers
      were relatively fewer among "high" consumers. Controlling for socio-economic
      group, there were twice as many men than women among "low" consumers. In
      conclusion, there was relative equality in the dental care delivery in this 50
      year old Swedish population, with some remaining social differences, primarily
      socio-economically contingent.

PMID- 8871019
TI  - Patterns of and reasons for tooth extractions in general dental practice in
      Ontario, Canada.
AB  - While substantial proportions of the population of Ontario, Canada continue to
      have teeth extracted, little is known about the reasons for this loss. In this
      survey of Ontario general dental practitioners, 128 dentists provided information
      on 6143 patients they saw during a reference week. Approximately one-in-seven of
      these patients had or were going to have one or more extractions as part of their
      current course of treatment. The mean number of extractions for patients having
      at least one tooth taken out was 2.3 (SD = 2.5). Emergency patients were more
      likely than regular patients to have at least one extraction but, on average, had
      fewer teeth taken out. Orthodontic considerations were the main reason for tooth
      loss in childhood, caries continued to be an important cause of tooth loss at all
      ages and periodontal disease accounted for more teeth lost after 40 years of age
      than caries. This study differs from almost all others in finding that, overall,
      more permanent teeth were extracted because of periodontal disease than because
      of caries. The former accounted for 35.9% of teeth lost and the latter for 28.9%.
      While this may be due to methodological differences between this and other
      studies, it is consistent with epidemiological data on periodontal disease in the
      Ontario population and data showing that Ontarians receive little in the way of
      periodontal care.

PMID- 8871020
TI  - Demand for and utilization of dental services among Hong Kong employees with and
      without dental benefit coverage.
AB  - The objectives of the present study were to investigate the effects of employer
      provided dental benefits on the pattern of demand for and utilization of dental
      services among Hong Kong employees and to analyse whether employees' awareness
      about an existing dental benefit programme influenced their dental service demand
      and utilization. Staff from 11 selected companies with and without dental
      benefits responded to questionnaires concerning their personal factors, demand
      for dental services, and utilization of dental services and about their awareness
      of their dental benefit coverage. Overall response rate was 67%. The socio
      demographic characteristics of those respondents who were covered and those who
      were not were similar. Forty per cent of the covered respondents were not aware
      of their dental benefit coverage, so analysis was performed with three groups of
      respondents, covered and aware, covered and unaware, and uncovered. A larger
      proportion of employees in the "aware" group had visited a dentist in the
      previous 12 months and had visited a dentist for asymptomatic reasons. The
      "aware" group reported more "low expenditure" items and less "high expenditure"
      items. Those who were aware of their dental benefit coverage irrespective of the
      type of scheme reported a significantly higher demand than those who were not
      aware of their coverage. Demand and utilization of the covered, but unaware,
      group was more similar to the uncovered group than to the "aware" group. Coverage
      per se had no apparent effect on the demand for dental services. Further studies
      will be necessary to establish that higher dental care demand and utilization
      induced by third party schemes also leads to improved oral health.

PMID- 8871021
TI  - 15-year evaluation of Class II amalgam restorations.
AB  - In a clinical trial, 1544 Class II amalgam restorations were inserted. In this
      study 1213 restorations were evaluated after 15 years and the reasons for
      replacement were registered. Attention was also paid to patient drop-out and
      patients' variables such as gender, filling degree, type of tooth (premolar vs
      molar), type of restoration (MO or DO vs MOD), jaw (upper vs lower) and the
      patients' operator. Furthermore, replacement rates of three alloys applied in
      comparable circumstances (n = 394) are reported. Of the restorations, 214 (17.6%)
      were replaced during the trial period. Factors influencing the replacement rates
      are gender, type of restoration and operator. Factors such as type of tooth and
      type of alloy seemed to have no influence on the replacement rates in this study.

PMID- 8871022
TI  - Analysis of adolescents' beliefs about the outcome of using dental floss and
      drinking non-sugared mineral water.
AB  - Using an expectancy value approach, personal and normative beliefs about the
      outcome of using dental floss and drinking non-sugared mineral water were studied
      in a sample of 970 15-year-old adolescents in the county of Hordaland in Norway.
      The data stem from a survey performed in October 1992. A detailed analysis of
      these beliefs provides information about which of them should be targeted in a
      persuasive communication directed at changing behavior. The adolescents evaluated
      six outcomes of each behavior in terms of how much they wanted or feared them,
      and rated the probability of each outcomes happening. The adolescents also rated
      the probability that four significant referents would approve the performance of
      each behavior and how much they valued the approval of each referent. Subjects
      with relatively strong and relatively weak intentions to use dental floss and to
      drink non-sugared mineral water (intenders and non-intenders) were compared with
      respect to their scores on each measure. A one-way analysis of variance showed
      consistent differences between intenders and non-intenders. Intenders were more
      likely to believe that the specified behaviors would result in positive outcomes
      and they evaluated these outcomes as more desirable than non-intenders. Intenders
      believed their referens, in particular dentists and parents, to be more concerned
      about whether or not to perform the specified behaviors than non-intenders. The
      most promising candidates for persuasive communication among behavioral beliefs
      with respect to the specified behaviors appeared to be reduced tooth decay and
      several non, health beliefs in terms of immediate social and sensory concerns.

PMID- 8871023
TI  - Dental malocclusion in native children of British Columbia, Canada.
AB  - Since 1972, the Medical Services Branch (MSB), Pacific Region of Health Canada,
      has conducted quadrennial surveys of the dental health status of Native children
      in British Columbia (B.C.), Canada. This paper will analyze the findings related
      to dental malocclusion. Data from the most recent survey in 1988 are compared to
      data from 1980, and also to similar data from the most recent B.C. Children's
      Dental Health Survey. Prevalences of abnormal and severe malocclusion are also
      compared to the original 1972 data. Methods used in the surveys were detailed in
      a previous paper (I). Significant decreases in the percentage of children with
      drifting due to premature space loss (P < 0.05), as well as a slight decrease in
      the percentage of children with crowding were observed. A trend towards an
      increase in Class II molar relationship was demonstrated, but was not consistent
      for all age groups. In contrast, there was a slight, but consistent, trend
      towards a decrease in the percentage of children with an anterior openbite.
      Comparisons between the age groups demonstrated an increased prevalence of
      abnormal molar relationship, drifting due to space loss, crowding, crossbite, and
      overjet greater than 4 mm in children older than 7 years. Native children had a
      significantly greater prevalence of Class III molar relationship, crossbite,
      crowding, negative overjet, and anterior openbite than other schoolchildren in
      B.C. (P < 0.05). However, percentage of Native children with a severe
      malocclusion decreased significantly from 1972 to 1988 for 7, 9, and 11 year old
      children (P < 0.05), but for 13 and 15-yr-olds. Improvement has occurred over
      time in some aspects of dental malocclusion in these Native Canadian children,
      but malocclusion continues to be a frequent problem, especially amongst
      adolescents.

PMID- 8871024
TI  - Variability in recording and grading the need for orthodontic treatment using the
      handicapping malocclusion assessment record, occlusal index and dental aesthetic
      index.
AB  - This investigation evaluates three malocclusion treatment need indices, the
      Handicapping Malocclusion Assessment Record (HMAR), the Occlusal Index (OI) and
      the Dental Aesthetic Index (DAI), for reliability and inter-index correlation.
      Pretreatment study models of 30 cases (mean age 12.9 years, SD 1.2) were assessed
      using each index. All the indices demonstrated a high level of reliability and
      non could be selected over the other with regards intra-examiner differences. The
      DAI, however, was more time-saving (2.68 mins, SD 0.41) and simple to use. The
      highest correlation was between HMAR and OI (r = 0.87, P < 0.001) which is a
      reflection of the similarity in their design. This study also discusses the
      limitations of the three indices.

PMID- 8871025
TI  - Caries experience and fluorosis prevalence in Chilean children from different
      socio-economic status.
AB  - Caries experience and enamel fluorosis prevalence in 8-year-old children
      belonging to different socio-economic classes were determined in two Chilean twin
      cities that are served by optimally fluoridated community water from the same
      waterworks facility. Low socio-economic status (LSES) children had a higher mean
      dmft and DMFT indices (P < 0.001) than high socioeconomic status (HSES) children.
      Prevalence of enamel fluorosis in the permanent teeth of LSES children was 0.79,
      significantly higher (chi 2 = 9.0; P < 0.003) than the value 0.59 found in HSES
      children. The proportion of Dean's scores 2, 3, 4 and 5 in first molars,
      mandibular and maxillary incisors in LSES children was higher than in HSES
      children (P < 0.001). Differences in prevalence and severity of enamel fluorosis
      between both groups are tentatively attributed to a different pattern of tap
      water and tea consumption at pre-school ages. Suggestions are advanced to
      minimize the undesirable prevalence and severity of enamel fluorosis.

PMID- 8871026
TI  - Impact on English dentists of the threat of HIV infection.

PMID- 8871027
TI  - The effect of fluoridation on populations in New Zealand.

PMID- 8871028
TI  - Is dental health education effective? A systematic review of current evidence.
AB  - In order that health service resources are allocated in the way which most
      benefits the population, systematic review of the available evidence regarding
      the effectiveness of programmes and interventions are required. This study
      examined papers relating to dental health education interventions, which were
      published between 1982 and 1994 (n = 143). Each was scored by two independent
      researchers according to twenty predetermined validity criteria. For each paper
      which achieved a validity score of more than 12 (n = 37), data concerning the
      objectives of the intervention, the types and numbers of participants, and the
      outcomes, were extracted from the article. Where sufficient data were provided in
      a paper which met more than 15 of the validity criteria quantitative meta
      analysis was carried out i.e. the results of the studies were pooled in order to
      calculate an overall intervention effect with confidence intervals. This
      combination of qualitative and quantitative review techniques showed that dental
      health interventions have: a small positive, but temporary effect on plaque
      accumulation (reduction in plaque index = 0.37 95% CI -0.29-0.59); no discernible
      effect on caries increment and a consistent positive effect on knowledge levels.
      The results of this analysis suggest that further efforts to synthesise current
      information about dental health education, in a systematic way, are required,
      along with maintenance of rigorous scientific standards in evaluation research.

PMID- 8871029
TI  - Structural comparison of a translated dental attitude questionnaire: a factor
      analytic study.
AB  - In 1984 the Dental Attitude Questionnaire (DAQ), an instrument for assessing
      various aspects of a person's attitude toward oral health care, was presented by
      STOCKWELL & BANTING. The DAQ consists of six content scales, Cynicism, Health
      Concern, Motivation, Oral Function, Social Aesthetic and Susceptibility, and two
      validity scales, Halo and Infrequency. A Dutch translation was presented in 1986
      by HOOGSTRATEN & BROERS. In order to replicate the factor analysis on the
      original DAQ as reported by STOCKWELL & BANTING, the present study was
      undertaken. The results show a change in factor structure from a three factor
      solution to a two factor solution. A confirmatory factor analysis shows that the
      original three factor structure of the DAQ is not present in the data collected
      with the translated version. To account for this change, some possible reasons
      are discussed.

PMID- 8871030
TI  - Patients' expectations of an ideal dentist and their views concerning the dentist
      they visited: do the views conform to the expectations and what determines how
      well they conform?
AB  - A convenience sample of patients (n = 271) from community health centres and
      private clinics in different parts of Finland were recruited for this study
      through their dental clinic. Equal numbers of regular and irregular clients were
      invited to participate. Before the treatment procedure, each patient filled out a
      questionnaire with forty Likertian statements dealing with their expectations of
      an ideal dentist, and nine about their own background, i.e., age, sex, regularity
      of dental visits. basic and professional education, and occupation. After the
      treatment subjects described their treating dentists' behaviour using similar
      statements. In the analyses two approaches were applied. First, factor analyses
      with orthogonal varimax rotation were conducted with the data about the ideal and
      actual dentist. For the ideal dentist, five factors were extracted: 1) mutual
      communication, 2) fair support, 3) personal appearance, 4) preferred type of
      practice, and 5) blaming; and for the actual dentist 5 factors were extracted: 1)
      mutual communication, 2) pain control, 3) fair support, 4) personal appearance,
      and 5) preferred type of practice. The factor structures were found to be similar
      when they were compared with transformation analysis. This justified the second
      analysis where the differences between the ideal and the actual factor scores
      were compared. The expectations of the patients were met on all the other dentist
      characteristics except mutual communication and fair support. There were not many
      differences between subgroups of patients. In further studies, other background
      variables, such as previous experiences of the patients, should be considered in
      order to obtain a more complete explanation of the variation in satisfaction.
      More attention should be paid to the communication skills of the dentists.

PMID- 8871031
TI  - Ideal role behaviours as seen by dentists and patients themselves and by their
      role partners: do they differ?
AB  - The aim of this study was to determine whether patients and dentists differ in
      their ideal role expectations concerning each others behaviour. This was done by
      further analysing a set of data containing responses to 124 five-class Likertian
      statements about ideal role expectations and questions about the background of
      the respondents with regard to different aspects of the dentist-patient
      relationship. The study groups consisted of a representative sample of lay people
      and all dentists in the Finnish Provinces Kuopio and North Karelia. To extract
      areas of ideal role expectations for both dentists and patients, orthogonal
      factor analyses were applied to the data. To evaluate the dissimilarity of the
      structure of the factor analyses, rotated factor matrices were used to conduct
      transformation analysis. Similarities between the ideal role expectations of
      dentists and patients were studied. When studied with transformation analysis,
      the ideal role expectations of dentists and patients were found to differ for
      both the ideal patient and the ideal dentist. However, dentists and patients
      shared expectations concerning one characteristic of the ideal dentist i.e. the
      importance of mutual communication, which was also considered the most important
      characteristic of the ideal dentist. For the characteristics of the ideal
      patient, the two groups shared the same expectations concerning the manageability
      of the patient. Previous research has compared dentist and patient expectations
      based only on single statements. No reports based on factor analysed data have
      been published, but transformation analysis was found to provide a useful tool
      for statistical evaluation of the dissimilarity of the factor structures.

PMID- 8871032
TI  - Subsidized dental care improves caries status in male industrial workers.
AB  - The association between an employer-provided dental benefit scheme and dental
      status was studied in male industrial workers in southern Finland in 1994. A
      total of 325 workers (age 38-65 yrs) with access to subsidized dental care and
      174 controls completed a multiple-choice questionnaire followed by clinical
      examinations. One or more carious teeth was registered in 19% of the subsidized
      group and 50% of the controls (P < 0.001). For subjects with retained roots the
      proportions were 2% and 15%, respectively (P < 0.001). Among those with caries
      the mean number of carious teeth was 2.1 (SD 2.0) in the subsidized group, and
      3.2 (SD 3.8) in the control group (P < 0.05). The groups did not differ
      significantly in numbers of teeth or filled teeth. The probability of having one
      or more carious teeth was negatively associated with access to subsidized dental
      care, with a recall or check-up as the reason for the last dental visit, and with
      having had the last dental visit within the past two years. The results showed
      that the dental benefit scheme resulted in less untreated caries.

PMID- 8871033
TI  - Oral health and family characteristics of children attending private or public
      dental clinics.
AB  - The City of North York Public Health Department (NYPHD) operates a school-based
      dental programme that provides preventive and treatment services to children
      according to evidence-based practice guidelines. This programme and private
      dental practices (PDP) represent the only sources of dental care for children in
      North York. The purpose of our study was to compare the oral health and family
      characteristics of clients from the NYPHD and PDP using a dental examination and
      a parent interview. Results showed that NYPHD and PDP clients had similar levels
      of fluorosis, calculus, and periodontal health, but NYPHD clients had experienced
      greater levels of decay. Clients of the NYPHD and PDP also had significantly
      different family characteristics, many of which were significantly associated
      with the presence of one or more decayed primary or permanent teeth. Multivariate
      logistic regression identified mother's immigration history, past caries
      experience, and parents' rationale for scheduling their child's dental
      appointments as the principle risk makers for dental decay. When compared with
      PDP clients, the NYPHD serves higher-needs children who otherwise might not
      receive care.

PMID- 8871034
TI  - Physical and mental health related to dental amalgam fillings in Swedish twins.
AB  - In the past years increasing attention has been paid to possible adverse health
      effects of mercury exposure from dental amalgam fillings. To evaluate possible
      health effects from amalgam fillings, dental status registered by specially
      trained nurses was obtained from 587 subjects included in the ongoing Swedish
      Adoption/Twin Study of Aging (SATSA). Data on physical and mental health were
      collected and memory function tested. Mean age was 66 years (SD 9, range 46-89).
      In the entire material, 25% of the individuals had no own teeth and in the group
      with own teeth the median number of teeth surfaces filled with dental amalgam was
      15 (range 0-65). Analyses of associations between number of surfaces filled with
      dental amalgam and a number of scales estimating somatic and mental health and
      memory functions were performed both for the entire group and for individuals
      having at least 12 teeth. Regardless of the sample, no negative effects on
      physical or mental health were found from amount of dental amalgam, even after
      controlling for age, gender, education and number of remaining teeth. When using
      a co-twin control design with twin pairs discordant for amalgam exposure, no
      negative health effects associated with dental amalgam were detected. This study
      does not indicate any negative effects from dental amalgam on physical or mental
      health or memory functions in the general population over 50 years of age.

PMID- 8871035
TI  - Dutch dentists' conceptions of dental silver amalgam.
AB  - A sample of 468 dentists completed a questionnaire on their conceptions of
      amalgam. A minority (1-3%) reported that amalgam often causes toxic, galvanic
      and/or allergic side-effects. A considerably larger number (10-30%) stated that
      such side-effects 'sometimes' occur, while less respondents (6-11%) said they did
      not know. 60-80% said that such side-effects do not exist, or rarely. If a
      patient requested the removal of amalgam, one-third of dentists would do so often
      for cosmetic or toxic reasons, but only one-fifth in the case of a proven
      allergy. A very substantial percentage would not remove amalgam except for
      cosmetic reason. Substantial minorities thought that amalgam should not be used
      for pregnant women or children, or admitted that they did not know. The use of
      amalgam was rejected by 5%, while 9% could not decide whether they were for or
      against its use. Multivariate analysis reveals the existence of two dimensions in
      the data. The first dimension, referred to as "acceptance-of-amalgam", makes it
      possible to distinguish a subsample (about 9%) consisting of "rejectors-of
      amalgam". On the second dimension, referred to as "conviction", a subsample
      (almost 20%) of "doubters" can be discerned, alongside "convinced adversaries"
      (about 4%) and "convinced advocates" (some 25%). The majority of the respondents
      are thought to be more or less in favour of the use of amalgam.

PMID- 8871036
TI  - Factors influencing the frequency of bitewing radiography in general dental
      practice.
AB  - The aim of this study was to determine the influence of a range of patient and
      dentist factors on the prescription of bitewing radiography. A postal
      questionnaire of general dental practitioners working in the Birmingham and
      Manchester areas of England was used. Dentists were requested to score the
      influence of 15 factors upon their decision whether or not to take bitewing
      radiographs. Some of these factors were chosen to represent accepted "high caries
      risk" factors, some "low risk" factors, while others were chosen as they should
      be irrelevant to prescription of bitewing radiographs. There was a questionnaire
      response of 70.8%. Dentists recognized accepted high caries risk factors as being
      an indicator for bitewing radiography but the influence of low caries risk
      factors was less clear. Only "good oral hygiene" and the presence of "few
      restorations" were perceived as relevant to bitewing prescription, while fissure
      sealants were seen as an influence in favour of radiography by almost one third
      of dentists. Dentists tended to be influenced in their radiographic practice by
      the opinions of patients and fears of medico-legal consequences. Pregnancy was
      seen as contra-indicatory for bitewings by almost all dentists. These results
      suggest that greater emphasis should be placed upon radiographic selection
      criteria in dental education.

PMID- 8871037
TI  - Evaluation of preventive treatment by risk of caries among 13-year-olds.
AB  - Implementation of caries preventive treatment in relation to the risk of caries
      was studied among 13-year-olds (n = 132) in two groups treated in the same public
      dental clinics in Helsinki: caries patients (n = 100) had the greatest numbers of
      decayed teeth (DT+dt), 5.5 on average, whereas cavity-free patients (n = 32) had
      intact teeth. Data taken from patients' personal oral health records served for
      evaluation of individual need for caries prevention, risk of caries, and
      preventive treatment given to each patient. Patients with any caries lesions or
      erupting teeth or poor oral hygiene were considered to be at risk of caries and
      in need of preventive treatment. The more caries lesions a patient had, the more
      prevention was expected to have been given. Preventive treatment of caries was
      weakly or only moderately in accordance with patients' individual needs and risk
      of developing caries, although patients with more caries lesions tended to have
      been given more preventive treatment than did those with none or only a few
      lesions. The majority of preventive measures given were applications of fluoride
      varnish, whereas motivation of and instruction in oral health care habits
      remained weak. However, patients whom their dentists had judged to be at high
      risk of caries received more intensified preventive treatment than did other
      caries patients. As a conclusion, intensification of caries prevention among high
      risk patients is still needed. Dentists should always consider each patient's
      risk of developing caries to improve quality of preventive treatment.

PMID- 8871038
TI  - Dental caries in Danish children and adolescents 1988-94.
AB  - The present study is based on data reported from the Danish Municipal Oral Health
      Service for children and adolescents to the National Board of Health from 1988 to
      1994. Only data from municipalities with public clinics for children and
      adolescents and only age-groups for which reporting was compulsory are included.
      When each cohort was followed during the years 1988 to 1994, it was shown that
      caries increment had only decreased slightly in both the deciduous dentition
      (from 3 to 6 yr) and in the permanent dentition (from 7 to 15 yr) during the
      beginning of the period and was now almost identical from one cohort to the next.
      The distribution of individuals in four selected age-groups according to defs and
      DMFS has become constant during the late 1980s and the early 1990s. It is
      concluded that the constant decrease in dental caries in Danish children and
      adolescents observed during the 1970s and early 1980s has now come to a halt.

PMID- 8871039
TI  - Case-control study of non-carious cervical lesions.
AB  - An exploratory case-control study of non-carious cervical lesions was undertaken
      to examine the effects of a variety of risk factors. Candidate exposure variables
      were related to erosion, abrasion, and tooth flexure, the three principal
      putative causal mechanisms for cervical lesions. Because previous studies have
      tended to focus on specific causal mechanisms, evidence for a multifactorial
      etiology is inconclusive. Data describing exposure factors were obtained through
      clinical examination, dietary and behavioral questionnaires, and analysis of
      study casts from 264 subjects (137 cases, 127 control). Salivary data were also
      obtained for a subset of these subjects. Patient and tooth-level logistic
      regression models were constructed for the full subject group, and the subset
      with salivary data. For the two patient-level models, only exposures related to
      brushing entered. For tooth-level models, multiple exposures representing all
      three causal mechanisms were included in both models. The results suggest that
      non-carious cervical lesions do have a multifactorial etiology, and that multiple
      causal mechanisms may operate in the initiation and progression of individual
      lesions.

PMID- 8871040
TI  - Fear of injections and report of negative dentist behavior among Caucasian
      American and Taiwanese adults from dental school clinics.
AB  - Fear of injections and reports of negative dentist behavior and associations with
      dental anxiety and avoidance of treatment were explored among 951 adults from
      dental school clinics in Iowa City, Iowa and Taipei, Taiwan. Use and fear of
      anesthetic injections and negative dentist behavior were assessed by written
      questionnaire to test associations with demographics, overall dental anxiety
      (Dental Anxiety Scale or "DAS") and utilization behaviors. Frequency and logistic
      regression analyses showed that use of dental anesthetics for routine treatment
      was much greater overall among caucasian Americans than Taiwanese, as was fear of
      injections. Taiwanese and Americans with high dental anxiety (DAS 12) had similar
      high fear of injections, but inspite of similar fears about dental drilling, high
      anxiety Taiwanese reported using much less local anesthesia for routine
      treatments than did high anxiety Americans. Report of condescending remarks to
      patients ("put downs") by dentists was mainly an American phenomenon associated
      with high dental anxiety. Avoidance of appointment making was high for persons
      afraid of injections and for Americans reporting negative dentist behavior.
      Avoidance was highest in subjects with high dental anxiety. That predominant
      characteristics or etiologies of dental anxiety can differ by cultural
      differences in dental health care systems, dentist beliefs and/or expectations of
      patients within those systems was discussed in relation to the literature.

PMID- 8871041
TI  - Oral soft tissue lesions in a black pre-school South African population.

PMID- 8871042
TI  - Caries experience in a selected patient population in Mexico City.

PMID- 8871043
TI  - Tooth loss and coronal caries of elderly residents in Singapore.

PMID- 8871044
TI  - Immunoregulation of asthma. II. Introduction.

PMID- 8871045
TI  - Modulation of the human IgE response.
AB  - Studies on the immunological basis of allergic diseases have indicated that
      enhanced production of the cytokines interleukin (IL)-4 and IL-13 and the reduced
      production of interferon-gamma (IFN-gamma) by allergen-specific T-cells
      contribute to enhanced immunoglobulin E (IgE) synthesis and the development of
      allergic disease in certain individuals. Therefore, inhibition of IL-4 and IL-13
      synthesis or blocking of activities of these cytokines would be one approach to
      inhibiting IgE production. In the present communication, novel approaches toward
      this goal are discussed. It is shown that an IL-4 mutant protein, in which the
      tyrosine residue at position 124 is replaced by aspartic acid (IL-4,Y124D), binds
      with high affinity to the IL-4 receptor, without receptor activation. IL-4,Y124D
      acts as a potent antagonist both of IL-4 and IL-13 activity in vitro, and
      inhibits immunoglobulin G4 (IgG4) and IgE production induced by these cytokines.
      These data are compatible with the notion that the IL-4 and IL-13 receptors are
      complex receptors, which share a common component, which is required for signal
      transduction. In addition, it has been demonstrated that allergen-specific T
      cells, belonging to the T-helper 2 (Th2) subset can be rendered anergic after
      incubation with allergen-derived peptides representing minimal T-cell activation
      inducing epitopes. These anergic Th2 cells failed to produce IL-4 and IL-13, and
      failed to proliferate after activation with allergen and antigen-presenting cells
      (APC). The anergized T cells also failed to give B-cells help in IgE synthesis,
      although they expressed normal levels of the CD40 ligand (CD40L). Exogenous IL-4
      and IL-13 failed to restore IgE synthesis, indicating that in addition to CD40L
      other co-stimulatory signals are required for productive T-cell/B-cell
      interactions, resulting in IgE synthesis. IgE production was restored by
      exogenous IL-2, demonstrating that IL-2 reverses the nonresponsive state and
      helper function of these nonresponsive T-cells. It is tempting to speculate that
      induction of T-cell nonresponsiveness by allergen-derived peptides may represent
      the underlying mechanisms for successful immunotherapy in allergenic patients.

PMID- 8871046
TI  - Pairs of surface molecules involved in human IgE regulation: CD23-CD21 and CD40
      CD40L.
AB  - At least two cell-derived signals have been shown to be necessary for the
      induction of immunoglobulin isotype switching in B-cells. The first signal is
      given by either of the soluble lymphokines, interleukin (IL)-4 or IL-13, which
      induce germline epsilon transcript expression, but this alone is insufficient to
      trigger secretion of immunoglobulin E (IgE). The second signal is provided by a
      physical interaction between B-cells and activated T-cells, basophils and mast
      cells, and it has been shown that the CD40/CD40 ligand (CD40L) pairing is crucial
      for mediating IgE synthesis. In hyper-immunoglobulin M1 (HIGM1) syndrome, which
      is characterized by greatly decreased levels of immunoglobulin G, A and E (IgG,
      IgA and IgE), there are mutations in the CD40L resulting in a completely non
      functional extracellular domain. The CD40L is, therefore, playing a central role
      in immunoglobulin isotype switching. Amongst the numerous pairs of surface
      adhesion molecules, the CD23-CD21 pair seems to play a key role in the generation
      of IgE. The CD23 molecule is positively and negatively regulated by factors which
      increase or decrease IgE production, respectively. Antibodies to CD23 have been
      shown to inhibit IL-4-induced human IgE production in vitro and to inhibit
      antigen-specific IgE responses in a rat model, in an isotype selective manner.
      CD23 interacts with CD21 on B-cells, preferentially driving IgE production. CD23
      recognizes two main epitopes on the CD21 molecule. One region consists of short
      consensus repeat (SCR) sequences 1-2 and the other of SCR 5-8. In the latter
      region, Asn 370 and 295 are critical in the interaction with the lectin CD23.
      Therefore, a restricted number of cytokines and surface molecules seems to
      selectively regulate human immunoglobulin E synthesis.

PMID- 8871047
TI  - Role of IL-4 in persistent IgE formation.
AB  - Antigen-specific immunoglobulin E (IgE) responses against T-cell-dependent
      antigens, like allergens, can only be generated by cognate interaction between B
      cells and T-helper (Th2) cells. This interaction is a prerequisite, donating the
      two signals that are essential for IgE production: CD40 ligation with its ligand
      gp39 and exposure to interleukin (IL)-4. Cytokine-mediated immunotherapy geared
      at intervention in allergic diseases, therefore aims at inhibiting the production
      or action of IL-4. In our view, based on two findings, this approach is
      simplistic. The first is that anti-IL-4 based approach (by complex formation
      between IL-4 and soluble IL-4 receptors or serum binding proteins) may actually
      increase the persistence of IL-4 and its effects instead of inhibiting them.
      Secondly, we have good evidence in mouse model systems that a period of exposure
      to IL-4 will result in an increased population of gamma 1,epsilon-double positive
      B-cells allowing an increased serum IgE level to persist for extensive periods of
      time. These B-cells turn out to be partially independent of IL-4 for their IgE
      formation. Moreover, these B-cells are partially independent of a cognate
      interaction with T-cells for their subsequent IgE synthesis. Therefore, we
      hypothesize that an approach geared solely at inhibiting IL-4 is not sufficient
      for decreasing persistent IgE levels in allergic patients.

PMID- 8871048
TI  - T-cell/eosinophil interactions in the induction of asthma.
AB  - There now exists considerable support for the hypothesis that asthma represents a
      specialized form of cell-mediated immunity, in which cytokines and possibly other
      mediators secreted by activated T-lymphocytes bring about the specific
      accumulation and activation of eosinophils in the bronchial mucosa. This
      observation has very important implications for future asthma therapy, since it
      suggests that drugs other than glucocorticoids which inhibit T-lymphocyte
      function may be of therapeutic benefit, as has recently been shown in the case of
      cyclosporin A. Further documentation of the cytokines involved in asthma of
      varying clinical associations might allow a pathophysiological classification of
      the disease.

PMID- 8871049
TI  - Antigen processing: approaches for dissecting subcellular mechanisms that form
      the basis for T-cell responses modulating allergic reactions.
AB  - Antigen processing determines the production of peptides from antigens, including
      allergens, and their binding to class II major histocompatibility complex (MHC
      II) molecules, which stimulate T-cell responses. Our studies have addressed the
      cell biology and biochemistry of the MHC-II antigen processing pathway using
      subcellular fractionation of macrophages on Percoll density gradients, coupled
      with other techniques. We have isolated a high density, late endocytic antigen
      processing compartment, with lysosomal properties, that contains a high level of
      MHC-II molecules, as assessed by several techniques. Moreover, the direct
      formation of peptide MHC-II complexes was demonstrated within this compartment,
      using a T hybridoma assay for peptide MHC-II complexes present in subcellular
      fractions of macrophages previously exposed to the model antigen, hen's egg-white
      lysozyme. These observations support an important role for this compartment in
      the class II major histocompatibility complex antigen processing pathway.

PMID- 8871050
TI  - Immunoregulation of the allergic reaction in the respiratory tract.
AB  - The nature of host responsiveness to inhaled antigens is now believed to be a
      direct reflection of the type of T-cell which dominates specific immunological
      "memory"; a predominantly Th2-like response potentially leading to allergic
      reactivity, versus apparent "unresponsiveness" if the memory pool is dominated by
      Th1 cells. The animal model literature suggests that potentially life-long
      dominance of immune responses to individual allergens is established at or around
      the time of first exposure, and involves an antigen-driven T-cell selection
      process. In humans, this process is likely to occur for most inhalant allergens,
      during early childhood. The outcome of these initial responses can be influenced
      by a variety of factors, including the nature and competence of the antigen
      presenting cells involved, the functional maturity of the CD4+ T-cell population
      at the time of exposure, and the presence of inflammatory or infectious stimuli
      at the level of the airway mucosa, which can effect the cellular and/or cytokine
      milieu within local draining lymph nodes. Recent studies from the animal models
      additionally indicate that the cytokine products from allergen-responsive major
      histocompatibility (MHC) class I restricted CD8+ T-cells, and also from allergen
      responsive T-cell receptor 1 (TcR1) (gamma/delta) T-cells, play an important role
      in shaping emerging CD4 T-cell responses, via the creation of an interferon-gamma
      (IFN-gamma)-rich milieu which selects against Th2 cells. The key finding from
      these studies is that these regulatory mechanism(s) function optimally in the
      relatively early stages of immune responses, and are considerably less effective
      in deviating established (memory) responses. It is argued below that the
      potential exists for exploitation of this information for the development of
      novel immunoprophylactic strategies to prevent primary allergic sensitization in
      humans at a stage when allergen-specific immune responses are theoretically most
      susceptible to regulation i.e. during early childhood.

PMID- 8871051
TI  - Modulation of T-cell cytokine secretion by accessory cell-derived products.
AB  - Several major pathological characteristics of atopic disease are causally related
      to CD4+ allergen-specific type 2 T-helper (Th2) cells with an aberrant cytokine
      secretion profile, comprising high levels of interleukin (IL)-4 and IL-5 and low
      levels of interferon (IFN)-gamma. Although the cytokine secretion patterns of
      CD4+ T-cells may be stable, they can be modulated by physiological factors which
      may be expected to be present during activation of these T-cells. In this review,
      we will focus on two secretion products of professional antigen presenting cells
      (APCs) and accessory cells with opposite modulatory effects on T-cell cytokine
      profiles, i.e. prostaglandin E2 (PGE2) and IL-12. PGE2 favours Th2-like cytokine
      secretion profiles by inhibiting the production of the Th1-associated cytokines,
      IL-2 and IFN-gamma, and in the presence of sufficient levels of IL-2,
      upregulating the production of the Th2-associated cytokines, IL-4 and IL-5, IL
      12, on the other hand, induces and enhances IFN-gamma secretion in activated CD4+
      T-cells, thereby promoting the generation of Th1 cells. PGE2 and IL-12 act via
      independent mechanisms and, therefore, do not mutually interfere with their
      modulatory effects. These data suggest that the relative contribution of PGE2 and
      IL-12 to the levels of secreted Th1- and Th2-associated cytokines are determined
      by their concentration ratio during T-cell activation.

PMID- 8871052
TI  - Cytokine production by T-cell clones from bronchoalveolar lavage fluid of
      patients with asthma and healthy subjects.
AB  - Cytokines produced by T-lymphocytes play an important regulatory role in
      inflammation in the airways of asthmatic patients. Our aim was to analyse the
      cytokine production by T-cell clones from bronchoalveolar lavage fluid (BAL) of
      patients with allergic asthma and the cytokine production of clones from the
      patients' peripheral blood (PB), as well as from BAL and blood from healthy
      controls. In 75 randomly selected CD4+ T-cell clones, we assessed the production
      of interleukin (IL)-2, IL-4 and interferon-gamma (IFN-gamma). After stimulation
      with anti-CD3, the clones from the asthmatic patients' BAL (A-BAL) produced
      significantly more IL-4 and IFN-gamma (median 0.32 and 4.17 ng.mL-1,
      respectively) than clones from A-PB (0.11 and 1.12 ng.mL-1, respectively). No
      evidence was found for a dominance of a type 1 or type 2 T-helper cell (Th1- or
      Th2)-cytokine profile in any of the groups. In three out of nine clones tested,
      the stimulation with anti-CD2/CD28/phorbol myristate acetate (PMA) induced a
      shift of the IFN-gamma/IL-4 ratio towards a Th2-type cytokine profile. Our
      results suggest that the clones from the asthmatic patients' bronchoalveolar
      lavage were derived from a more differentiated T-cell population. In several
      clones, the cytokine profile was still modulated by the stimulus applied.
      Similarly, local conditions in the airways may be involved in directing the
      cytokine production of T-cells.

PMID- 8871053
TI  - The role of alpha 4 integrins in lung pathophysiology.
AB  - The alpha 4 integrins are heterodimeric leucocyte cell surface molecules central
      to their cell and matrix adhesive interactions. The integrin alpha 4 beta 1
      interacts with the immunoglobulin superfamily member vascular cell adhesion
      molecule-1 (VCAM-1), and with an alternatively spliced form of fibronectin. The
      integrin alpha 4 beta 7 binds not only VCAM-1 and fibronectin, but also the
      mucosal addressin cell adhesion molecule (MAdCAM). Certain monoclonal antibodies
      (MoAbs) to the alpha 4 chain of alpha 4 beta 1 and alpha 4 beta 7 can block their
      in vitro adhesive function. In vivo studies with these MoAbs in lung antigen
      challenge models in several species demonstrate that alpha 4 integrins play a key
      role in eosinophil and T-cell recruitment, in the late phase response, and in
      airways hyperresponsiveness. In particular, MoAb HP1/2 is efficacious in a sheep
      model of allergic airways challenge, whether given intravenously or as aerosol.
      To evaluate the mechanism of action of this MoAb, Fab fragments were generated
      and shown to be equipotent in vitro and as efficacious in vivo as the intact
      immunoglobulin G (IgG). These data demonstrate that the in vivo efficacy of
      monoclonal antibody HP1/2 is not due to indirect effects, such as antigen cross
      linking, but rather to blockade of alpha 4 integrin adhesive function. Humanized
      monoclonal antibody or other alpha 4 integrin antagonists may provide novel
      therapeutics for asthma.

PMID- 8871055
TI  - IgE receptor (Fc epsilon RI) and signal transduction.
AB  - This review suggests a model in which both beta- and gamma-chains synergize in
      the initiation of Fc epsilon RI signal transduction function. Receptor
      aggregation by antigens induces activation of lyn, which is already bound to the
      Fc epsilon RI beta-chain under resting conditions. Whilst activated, lyn would
      phosphorylate the tyrosine residues in the Fc epsilon RI gamma-chain. This
      phosphorylation would be responsible for the recruitment of syk (probably via its
      SH2 domains) as well as other signalling molecules. Syk kinase would then be
      activated by the engagement of its SH2 domains and/or its phosphorylation. Syk
      could then interact with and activate (through phosphorylation) downstream
      effector molecules.

PMID- 8871054
TI  - Role of the eosinophil in allergic reactions.
AB  - The eosinophil may have several functions in health and in the pathogenesis of
      allergic and other diseases. Some roles of the eosinophil are based on the acute,
      effector responses of this cell, its capacity to generate biologically active
      lipid mediators and release its granule contents, including its distinctive
      cationic proteins. Whilst the effector responses of eosinophils are important for
      their contribution to the acute pathogenesis of allergic diseases, a fuller
      understanding of the eosinophil requires evaluation of the role this cell may
      play at tissue sites, especially submucosal sites, where the cell is normally
      localized in the absence of disease. Moreover, for the long-lived, tissue
      resident eosinophil, definition of the interactions that occur between the
      eosinophil and other immune cells is germane to understanding the functions of
      eosinophils both in acute and chronic diseases. Many allergic diseases are
      characterized by heightened accumulation of eosinophils and are chronic ongoing
      diseases.

PMID- 8871056
TI  - Eosinophil priming by cytokines: from cellular signal to in vivo modulation.
AB  - Eosinophils play an important role in the effector phase of allergic
      inflammation. This review will focus on the conversion of the unprimed eosinophil
      phenotype in the peripheral blood of normal individuals to the primed phenotype
      found in the peripheral blood and tissues of allergic patients, a phenomenon
      called priming. Recent data on the signals initiated after cytokine receptor
      activation on eosinophils will be reviewed.

PMID- 8871057
TI  - The role of basophils in allergic disease.
AB  - During allergic disease, leucocytes infiltrate the affected tissues and release
      their mediators and cytokines. In this way, the local inflammatory process is
      induced and maintained. Basophilic granulocytes have been demonstrated in lung
      and sputum of allergic asthmatics, in nasal mucosa and secretion of allergic
      rhinitis patients, and in skin lesions of atopic dermatitis patients. The number
      of basophils correlates with the severity of the disease. Analysis of mediator
      profiles and cellular contents of lavages of nose, skin and lung during allergic
      late-phase reactions (LPR) have demonstrated histamine, but not tryptase or
      prostaglandin D2. The histamine-containing cells have been characterized as
      basophilic granulocytes. This indicates that infiltrating basophils but not mast
      cells are activated and release their inflammatory contents in the LPR. We are
      interested in the cellular mechanisms that determine the degranulation of
      basophils during LPR. Basophil activators, such as allergens and activated
      complement, are not present at these sites. However, cytokines that prime
      basophils but do not induce degranulation, such as interleukin-5 (IL-5) and
      granulocyte/macrophage colony-stimulating factor (GM-CSF), have been detected at
      sites of LPR. We have now observed that after emptying intracellular Ca2+ stores
      by means of the Ca2+ adenosine triphosphatase (ATPase) inhibitor, thapsigargin,
      basophils become extremely sensitive to stimuli that do not affect the Ca2+
      stores themselves but that induce degranulation, such as the phorbolester,
      phorbol myristate acetate (PMA). The most interesting finding was that although
      both thapsigargin and IL-3, IL-5 or GM-CSF do not induce basophil degranulation
      by themselves, a 2 min preincubation of basophils with thapsigargin followed by
      addition of one of these cytokines resulted in extensive histamine release: IL-3
      induced 71 +/- 7% histamine release (conc1/2max 6 pM), IL-5 induced 43 +/- 8%
      histamine release (conc1/2max 41 pM) and GM-CSF induced 57 +/- 10% histamine
      release (conc1/2max 140 pM). Interestingly, the effect of thapsigargin could be
      mimicked by platelet-activating factor (PAF) (range 10(-9) to 10(-6) M), although
      to a lesser extent. Our results indicate that basophil degranulation in tissues
      during late-phase reactions might be caused by a combination of mediators or
      cytokines depleting Ca2+ stores, as platelet-activating factor or thapsigargin
      do, concurrent with activation by interleukin-3, interleukin-5 or
      granulocyte/macrophage colony-stimulating factor. The response of the basophils
      towards these cytokines might also be influenced by cell adhesion events, such as
      binding of basophils via integrins. This is the subject of further study.

PMID- 8871058
TI  - Characteristics of airway eosinophils.
AB  - Eosinophils are important participants and contributors to allergic inflammation
      in asthma. The mechanisms by which eosinophils migrate to the airway and are
      activated are not clear. Moreover, there is evidence that eosinophils from the
      airway are functionally distinct from those cells in circulation. In initial
      studies, we have found distinct differences in function, cell surface markers,
      calcium metabolism in response to activation, and survival in eosinophils from
      the airway. In an attempt to ascertain what factors regulate these phenotypic
      changes, we have evaluated the effect of cytokines and adhesion on eosinophil
      function.

PMID- 8871059
TI  - Mechanisms regulating eosinophil extravasation in asthma.
AB  - Infiltration of eosinophils into tissue allergic inflammation is mediated by a
      combination of processes. Eosinophil L-selection and very late activation antigen
      (VLA-4) can selectively regulate eosinophil adhesion to the endothelium.
      Activating cytokines, such as interleukin (IL)-5, regulated upon activation in
      normal T-cells (RANTES) and monocyte chemotactic peptide (MCP)-3 specifically act
      on eosinophils. Moreover, eosinophils from allergic individuals can be primed for
      increased adhesion and movement by chemokines released at sites of allergic
      inflammation. Together, these processes induce a specific infiltration of
      eosinophils.

PMID- 8871060
TI  - The effect of salmeterol and nimesulide on chemotaxis and synthesis of PAF and
      LTC4 by human eosinophils.
AB  - Salmeterol is a long-acting beta 2-adrenoceptor agonist, with several antiasthma
      properties. Nimesulide is a nonsteroidal anti-inflammatory drug, supposed to act
      by inhibition of phosphodiesterase type IV. This might indicate that the effects
      of both drugs are mediated by an increase in cyclic adenosine monophosphate
      (cAMP). For salmeterol, it has been shown that it inhibits the influx of
      eosinophils into the lungs of guinea-pigs after platelet-activating factor (PAF)
      challenge, suggesting an effect of cAMP on eosinophil migration. For neutrophils,
      it has been shown that PAF synthesis is inhibited by cAMP. In the present study,
      we have, therefore, measured the effect of salmeterol and nimesulide on two
      important human eosinophil functions: chemotaxis; and synthesis of PAF and
      leukotriene C4 (LTC4). Both drugs were found to be inhibitors of the chemotactic
      responses of human eosinophils. However, at comparable concentrations, only
      nimesulide was able to inhibit the synthesis of PAF and LTC4 in activated
      eosinophils. These results indicate that although the effects of both drugs are
      thought to be mediated by an increase in cyclic adenosine monophosphate, they
      have differential effects on eosinophil chemotaxis and synthesis of lipid
      mediators.

PMID- 8871061
TI  - Molecular mechanisms of steroid action: a novel type of cross-talk between
      glucocorticoids and NF-kappa B transcription factors.
AB  - Despite the widespread use of glucocorticoids in the treatment of diseases
      characterized by inflammation, the molecular mechanism(s) by which these hormones
      exert this beneficial effect in patients with asthma remains to be elucidated.
      Therefore, we have studied the transcriptional regulation of intercellular
      adhesion molecule-1 (ICAM-1) as adhesion molecules are likely to play a causal
      role in inflammation in promoting cell-cell and cell-matrix interactions. We
      observed that in a monocytic (U937) and a bronchial epithelial (H292) cell-line
      dexamethasone strongly suppressed basal and induced ICAM-1 expression. Subsequent
      analysis of the human ICAM-1 promoter has revealed that both 12-O
      tetradecanoylphorbol 13-acetate (TPA) and tumour necrosis factor-alpha (TNF
      alpha) upregulate ICAM-1 expression through the presence of a nuclear factor (NF
      kappa B) target sequence (TGGAAATTCC). No glucocorticoid recognition sequences
      are present in this promoter region and dexamethasone is still able to repress
      transcription when the multimerized NF-kappa B sequence is transactivated by TNF
      alpha upon transfection in 293 cells. We propose that direct interaction between
      the glucocorticoid receptor and nuclear factor-kappa B factors is at least a
      partial explanation for the effects of this hormone in inflammatory diseases.

PMID- 8871062
TI  - Immunomodulation as asthma therapy: where do we stand?
AB  - There is increasing evidence that chronic inflammation in asthma is mediated via
      a network of cytokines emanating from inflammatory and structural cells in the
      airways. The prominent eosinophilic inflammation that characterizes asthma
      appears to be orchestrated by cytokines derived from type 2 T-helper (Th2)-like
      lymphocytes, suggesting that immunosuppressants might be beneficial in the
      control of asthma. Indeed, one of the critical modes of action of glucocorticoids
      in controlling asthma may be the suppression of Th2-lymphocyte-derived cytokines,
      such as interleukin-5 (IL-5). Cyclosporin-A may have a similar immunomodulatory
      role, but its potential beneficial effects are outweighed by its toxicity, at
      least when given parenterally. Future immunomodulators need to be more selective,
      either by means of delivery (inhalation, liposomes) or by a more specific effect
      on Th2, as opposed to Th1, lymphocytes or their products. Such approaches may
      include new immunomodulators, such as mycophenolate mofetil, specific cytokine
      inhibitors (such as interleukin-5 antibodies), endogenous suppressors of Th2
      cells (interferon-gamma or interleukin-12), or type 4 phosphodiesterase
      inhibitors.

PMID- 8871063
TI  - Experimental induction of epithelial-mesenchymal interconversions.
AB  - Under some in vitro conditions, such as exposure to collagen, growth factors and
      related molecules, and agents affecting DNA methylation, a cell phenotype shift
      can be observed from an epithelial to a mesenchymal state of differentiation. The
      reverse process, a mesenchymal-to-epithelial conversion can likewise be obtained
      by certain experimental manipulations. In some instances the change is fully
      reversible by removing the inducer substances, but in others the conversion
      appears to be stable and irreversible. Only a partial modulation of the cell
      phenotype is often seen, but sometimes a complete switch to a new phenotype
      occurs, and morphological, biochemical and functional characteristics of the
      parent cells can be abrogated. In some in vivo models development of sarcomatous
      tumours can be seen in animals transplanted with several types of carcinoma, and
      it is possible that in some of these experiments an epithelial-to-mesenchymal
      conversion has occurred too. In normal embryonic development as well as in
      pathological lesions including tissue repair, tumour invasion, and some malignant
      biphasic tumours, changes similar to the ones observed in experimental epithelial
      mesenchymal interconversion seem to take place. Therefore, it is conceivable that
      experimentally-induced phenotype conversions reflect an inherent potential of
      cells, and that under some experimental circumstances normally silent genetic
      programs for epithelial or mesenchymal differentiation are activated, thus
      recapitulating a phenomenon that occurs in physiopathological circumstances in
      vivo.

PMID- 8871064
TI  - Ameloblastoma in a female Wistar rat.
AB  - A spontaneous ameloblastoma of the right mandible is described in a 120-week-old
      female Wistar rat (strain Chbb: THOM). The tumour had a locally aggressive growth
      pattern and was histologically characterized by sheets and islands of odontogenic
      epithelium bounded by a palisaded layer of ameloblast-like cells. Because of
      multifocal keratinizing squamous metaplasia of the stellate reticulum tissue, the
      tumour was classified as an acanthomatous ameloblastoma. Cyst formation, areas of
      stromal hyalinization and enamel matrix-like inclusions were further
      characteristics of the neoplasm. The epithelial elements stained strongly
      positive for broad spectrum cytokeratins.

PMID- 8871065
TI  - Confirmation that magnesium lithospermate B has a hydroxyl radical-scavenging
      action.
AB  - Male LWH: Wistar rats were given creatinine (Cr) intraperitoneally at a dose of
      1.00 g/kg body weight, and the urine was collected for 3 h after administration.
      Magnesium lithospermate B, a compound newly isolated from Salviae Miltiorrhizae
      Radix, was administered intraperitoneally 30 min before and 30 min after Cr
      administration. The excretion of urinary creatol and methylguanidine induced by
      Cr decreased in a dose-dependent manner. Since we have already shown that the
      main contributor to the Cr-->creatol oxidation step is the hydroxyl radical,
      magnesium lithospermate B may act as a radical scavenger.

PMID- 8871066
TI  - Effects of acetaminophen on the ultrastructure of isolated rat hepatocytes.
AB  - The effects of acetaminophen (AA) on the ultrastructure of isolated hepatocytes
      (IHC) of rat following incubation of IHC suspensions with AA were examined by
      electron microscopy. The effect of N-acetyl-p-benzoquinone imine (NAPQI), a
      putative toxic metabolite of AA, were also observed. IHC were prepared from
      livers obtained from phenobarbital-treated rats by collagenase perfusion method.
      With 5 and 20 mM AA, surface blebs mainly containing smooth endoplasmic reticulum
      (ER) occurred in IHC. Dilatation of Golgi apparatus, partial degranulation of
      rough ER and enlargement of mitochondria were also observed. The altered
      mitochondria showed a low electron-dense matrix with loss of mitochondrial
      granules. With 500 microM NAPQI, surface blebs containing various organelles
      occurred in IHC. Disorderly distributions of cytoplasmic organelles, mild
      dilatation of rough and smooth ER and cytoplasmic myeloid bodies were observed.
      The characteristic myeloid bodies were seemingly derived from degranulated rough
      ER.

PMID- 8871067
TI  - Increased sensitivity to bilateral nephrectomy in rat caused by endotoxemia.
AB  - In this study the possibility that the kidneys play a role in the removal of
      endotoxin from the blood was examined. This was carried out by an IP injection of
      endotoxin (at a dosage of 1 mg/100 gr) to rats that had undergone bilateral
      nephrectomy, and examining the times of death following various treatments.
      Furthermore, the rats underwent treatment for endotoxin tolerance or received
      treatment with the antioxidants superoxide dismutase (SOD) and natural
      antioxidant (NAO) or were injected with an inhibitor of the enzyme NOS (NGmethyl
      l-arginine 1-NMA). The endotoxin concentration in the plasma was also measured.
      The results of this study indicate the rats were more sensitive to bilateral
      nephrectomy in the presence of endotoxin. This increased sensitivity in the
      binephrectomized rat decreases following treatment inducing tolerance to
      endotoxin, or following treatment with an antioxidant or with the inhibitor of
      NOS. A possible explanation for the increased sensitivity following endotoxin
      injection is that it apparently results from an increased concentration of
      endotoxin in the blood due to the impossibility of removing the endotoxin via the
      kidneys. Therefore, endotoxin tolerance or abolishing the potential injuries that
      may be caused by endotoxin negate the sensitivity in the binephrectomized rats
      injected with endotoxin.

PMID- 8871068
TI  - Effects of ethylene glycol on the ultrastructure of hepatocytes.
AB  - The ultrastructure of rat hepatocytes after acute experimental ethylene glycol
      poisoning was examined. On the 1st, 5th and 14th days after poisoning the
      material from the centrolobular zone (zone III) was collected. Proliferation and
      enlargement of SER at the early period of poisoning and evidence of mitochondrial
      damage both at the early and late time after ethylene glycol intoxication were
      found. In the liver extensive capillary deposits surrounded by membranes were
      seen, filled with flocculent material of middle electron density. The results
      show destruction of the cytoplasmic organelles, especially mitochondria, on the
      1st and 5th days after ethylene glycol intoxication, and symptoms of damage
      removing together with regeneration on the 15th day of the experiment.

PMID- 8871070
TI  - Effect of quinolinic acid administration on rat liver: ultrastructural
      investigation.
AB  - Quinolinic acid was administered intraperitoneally in a dose of 30 or 60 mmol,
      once every 24 h for 8 days. Its result in the dose of 30 mmol was the
      proliferation of smooth elements of the endoplasmic reticulum. The use of
      quinolinic acid in a dose of 60 mmol was characterized by the presence of more
      profound damage of organelles, among them the distinct decrease of the rough
      elements of the endoplasmic reticulum and polyribosomal structures was seen, and
      moreover, wide areas devoid of organelles were observed.

PMID- 8871069
TI  - Abnormal dendritic maturation of neurons under the influence of a Tilorone
      analogue (R 10.874).
AB  - Tilorone analogue (R 10.874) has a close affinity to the lysosomal compartment of
      cells and forms a non degradable carbohydrate-lipid-drug complex accumulated
      within digesting organelles. Resembling biochemical and structural changes are
      seen in hereditary mucopolysaccharidoses accompanied with abnormal
      dendritogenesis. On the other hand, developmental toxicity (TERRY et al. 1992),
      antiproliferative effects (ALGARRA et al. 1993) and interactions with DNA (GELLER
      et al. 1985) are generated by tilorone. Therefore it should be interesting to
      know whether the amphiphilic cationic compound is able to produce an abnormal
      dendritogenesis as in storage diseases or an impaired arborisation of dendrites
      and what could be the reason for the misdevelopment. We demonstrate that there
      was a fetal retardation in the development of dendritic network, even under
      influence of low dosis of the analogue R 10.874. The dendritic dismaturation was
      concomitant with an increased amount of fatty acids and a slightly disarranged
      metabolic pathway of gangliosides. The dendritic arborisation closed the gap of
      retarded development between intrauterine treated and untreated rats after 7 days
      of postnatal drug elimination. We suppose that a fetotoxic effect and not the
      lysosomopathy is responsible for the reduced dendritic network.

PMID- 8871071
TI  - Sephadex induced granulomatous reaction in rats.
AB  - Granuloma formation in the rat lung after single or repeated i.v. injections,
      intratracheal instillation and intradermal implantation of Sephadex beads was
      studied over a time period from 3 h to 3 mo. Macrophages were identified with the
      mAB ED1, vascular smooth muscle cells with an mAB against alpha SMC-actin,
      endothelial cells with a polyclonal AB against factor VIII and cyclic activity
      with an mAB against PCNA. The morphology and the time course of the development
      of the granulomas is identical in the different experimental conditions. The
      macrophages form the bulk of the cellular infiltrates, giant cells appear after
      24 h. Cyclic activity is early and marked in the interstitially located
      macrophages, it is delayed and slight around the beads, suggesting a biphasic
      pattern. The macrophage reaction is markedly enhanced after a second i.v.
      injection, indicating the development of a hypersensitivity state. Numerous
      eosinophils are located in the interstitium, but only few are in direct contact
      with the beads. Their number doesn't increase after a second i.v. injection.
      Intradermal implantations show only macrophages and lymphocytes. A special
      feature is the disappearance of the arterial wall around the beads resulting in
      extrusion without haemorrhages or thromboses.

PMID- 8871072
TI  - Reduction of risk following endotoxin injection in unilaterally nephrectomized
      rats.
AB  - In this study the consequences of unilateral nephrectomy on the survival rate of
      rats were examined under severe pathological conditions including injection of a
      lethal dose of endotoxin (exogenic LPS), cecal puncture (endogenic LPS),
      injection of LPS concomitantly with renal ischemia as well as a simultaneous
      injection of LPS and glycerol to the leg muscle in order to induce acute renal
      failure. Sham operated rats did not exhibit higher survival rates than the
      nephrectomized rats. In most cases there was even a decrease in the percent age
      rate of deaths in the nephrectomized rats. Improvement in the resistance of the
      nephrectomized rats to pathophysiological stress occurred when stress was induced
      immediately following nephrectomy as well as when stress was induced 30 days
      following nephrectomy. No significant differences were found in blood pressure,
      heart rate, hematocrit, rate of respiration and body temperature in the
      nephrectomized rats as compared to rats that did not undergo nephrectomy. A
      possible explanation for our results is that the solitary kidney excretes more
      LPS into the urine.

PMID- 8871073
TI  - Angiogenic activity in normal and dysfunctional uterine bleeding human
      endometrium; as measured by the chick chorioallantoic membrane assay.
AB  - The modified chick chorioallantoic membrane assay was used to measure the
      angiogenic activity of whole human endometrium, endometrial gland and endometrial
      stromal cell preparations. Specimens were studied from normal subjects and from
      those suffering from dysfunctional uterine bleeding. This was done in order to
      investigate possible sites of angiogenic factor synthesis in endometrium.
      Significant angiogenic activity was demonstrated in all three sites and was
      present in all phases of the cycle except for the late secretory phase specimens.
      In the late secretory phase, compared to the controls, there was no significant
      angiogenic activity in the whole endometrial, endometrial gland nor endometrial
      stromal cell preparations. There were no differences in angiogenic activities
      between the various phases studied apart from a significant decrease in
      angiogenic activity for the endometrial gland cell preparations between the
      midsecretory phase and the late secretory phase. This study suggests than human
      endometrium produces local angiogenic factors throughout the menstrual cycle and
      that these factors may decrease towards the end of the cycle. It has been
      suggested that dysfunctional uterine bleeding may be due to disturbances in local
      angiogenic factors produced in the endometrium. This study found no significant
      differences in angiogenic activities between normal endometrium and dysfunctional
      endometrium. This suggests that dysfunctional uterine bleeding may not be due to
      disturbances in local angiogenic factors.

PMID- 8871074
TI  - Modulation of cellular immunity by a lesion of the lateral hypothalamic area
      (LHA) in rats.
AB  - The subject of our investigation was the effect of bilateral damage to the
      lateral hypothalamic area (LHA) on the cellular immune response (CIR), assessed
      by measuring the diameter of skin infiltration (DSI) 24 and 48 h after
      intradermal administration of tuberculin in adult male Wistar rats, previously
      immunized with BCG vaccine. It has been shown that: 1) in the hypothalamo
      lesioned rats (HLR) DSI measured 24 and 48 h after tuberculinization did not
      differ, 2) in the sham-operated rats (SOR) DSI measured 48 h after tuberculin
      injection was significantly higher (p < 0.02) than that found 24 h after the
      antigen administration, 3) the damage-induced loss of body weight and the 24-48 h
      difference in DSI in the responders of the HLR group correlated negatively with
      each other (r = -0.806, p < 0.05). These results indicate that damage to the LHA
      enhances the rate of formation, but not the maximal size, of the tuberculin
      induced skin infiltration. Thus, the LHA seems to be involved in the
      regulation/modulation of processes engaged in the expression of tuberculin
      reaction.

PMID- 8871075
TI  - In vitro lead cation-hyaluronic acid interaction.
AB  - It is the purpose of this investigation to study the in vitro spontaneous
      interaction lead-hyaluronic acid using the equilibrium dialysis technique. The
      following working conditions were used: membrane retention capacity starting from
      12000 D; solvent was an aqueous buffer solution (pH 7.4); relation of internal
      external volume of 0.5 : 25 mL: dialysis time 24 hours; lead concentration in
      dialyzing solution 4 micrograms/mL (always outside the bag); temperature 4
      degrees C; concentrations of hyaluronic acid 0.3, 1.2, 2.1 and 3.0 mg/mL;
      concentration of plasma proteins 1.5 mg/mL; lead was determined in the internal
      solution of the bag, and was measured quantitatively by atomic absorption
      spectrometry. Testing separately hyaluronic acid and plasma proteins both types
      of marcromolecules turned out to bind lead. As the concentration of hyaluronic
      acid increases, the amount of lead retained increases as well, although this
      relation is only approximately linear. At the normal concentrations of plasma
      proteins and hyaluronic acid in synovial fluid, the proteins solution bound more
      lead than hyaluronic acid solution 16.2 +/- 2.1 and 5.7 +/- 0.4 micrograms/mL
      respectively (P < 0.0001). What these data show ist that both, hyaluronic acid
      and proteins are involved in the in vitro lead retention. The effect of both
      ligands must be synergistic, because when the two molecules are present, a higher
      amount of lead is retained compared to the amount bound separately, suggesting
      that lead can replace calcium by complexation with mucopolysaccharides; this
      explains the lead accumulation in synovial fluid since this fluid is rich in
      hyaluronic acid and proteins.

PMID- 8871076
TI  - Impairment of vitamin A uptake by rat hepatocytes and fat storing cells
      determined by Monensin--morphological observations.
AB  - The action of the Na+/H+ antiport monensin on vitamin A uptake by rat liver has
      been studied in vivo. The quickfading autofluorescence of vitamin A has been used
      for the determination of vitamin A uptake by the liver. Pretreatment of rats
      intraperitoneally with monensin decreases the uptake of vitamin A by hepatocytes
      and its transfer for storage to fat storing cells. Pretreatment of rats
      intraperitoneally with vitamin A for a short time, then with monensin, shows that
      the hepatocytes no longer transfer vitamin A to fat storing cells for storage.
      These results might indicate that monensin impairs the uptake of vitamin A by the
      hepatocytes and might also impair the transport of vitamin A from parenchymal to
      perisinusoidal cells.

PMID- 8871077
TI  - Urinary metabolite profile of PAH as a potential mirror of the genetic
      disposition for cancer.
AB  - Polycyclic aromatic compounds such as polycyclic aromatic hydrocarbons or
      aromatic amines presently are considerably underestimated with regard to the
      formation of environmentally caused cancer diseases. The individual urinary
      metabolite profile raising from the PAH inhaled is invariant. This holds for tar
      pitch aerosol exposed Wistar rats as well as for PAH-exposed workers. Significant
      individual differences of the urinary metabolite profile can be observed in
      different individuals. The differences reflect the different individual enzyme
      equipment. There is an individual correlation between the PAH-masses inhaled and
      the masses of their metabolites excreted in the urine; e.g. the excretion of
      phenanthrene varies from 5% to 20% for different coke workers. The PAH metabolite
      profile analysis appears to be a suitable tool to estimate the individual
      cancer.risk at PAH-exposed working places since the PAH-induced malign
      transformation is caused by specific PAH metabolites.

PMID- 8871078
TI  - Metabolism of polycyclic aromatic hydrocarbons in fetal human, rat and hamster
      epithelial lung cells.

PMID- 8871079
TI  - Concluding remarks: the view of occupational medicine.

PMID- 8871080
TI  - Establishment of in vitro systems from the respiratory tract of different species
      for the investigation of PAH metabolism.

PMID- 8871081
TI  - Risk estimation in coke-oven workers by determining some biomarkers of carcinogen
      exposure.

PMID- 8871082
TI  - Formation of O6-ethylguanine in spermatogonial DNA of adult Syrian golden hamster
      by intraperitoneal injection of diethylnitrosamine.
AB  - 17-Week-old Syrian golden hamsters received a single intraperitoneal injection of
      diethylnitrosamine (DEN) at a dose of 100 mg/kg body weight. The DNA alkylation
      product O6-ethylguanine was formed in the spermatogonia. The data demonstrate
      that DEN can pass the blood-testis barrier and be metabolized in the
      spermatogonia to yield an alkylating derivative or that externally activated
      metabolites themselves can pass the barrier.

PMID- 8871083
TI  - Early ultrastructural lesions of diphenylamine-induced renal papillary necrosis
      in Syrian hamsters.
AB  - The ultrastructural lesions of diphenylamine-induced renal papillary necrosis in
      Syrian hamsters were characterized by transmission electron microscopy. Twenty
      four male Syrian hamsters were orally administered 600 mg diphenylamine/kg body
      weight as a single dose. At 30 minutes and at 1, 2, 4, 8, 16 and 24 hours after
      administration of diphenylamine, three hamsters were anesthetized with
      pentobarbital, perfused via the left ventricle with half-strength KARNOVSKY's
      fixative, and the renal papilla and outer medulla collected. Three hamsters
      administered 0.5 ml peanut oil/kg body weight (vehicle controls) were
      anesthetized at 24 hours, perfused, and the renal papilla and outer medulla
      collected. Initial ultrastructural lesions were observed in the endothelial cells
      of the ascending vasa recta in the proximal portion of the renal papilla at 1
      hour after diphenylamine administration. The endothelial cell basal plasma
      membrane was elevated from the basal lamina, forming large subendothelial
      vacuoles. Alterations in inner medullary interstitial cells, endothelial cells of
      the descending vasa recta, and the epithelial cells of the thin limbs of Henle
      and the medullary collecting tubules were observed subsequent to the lesion in
      the ascending vasa recta. It was concluded that the endothelial cell of the
      ascending vasa recta is the target cell in diphenylamine-induced renal papillary
      necrosis in Syrian hamsters.

PMID- 8871084
TI  - Ultrastructural changes in 9-day old mouse embryos following maternal tobacco
      smoke inhalation.
AB  - Mice were exposed to tobacco smoke inhalation for three ten-minute episodes on
      days 6, 7 and 8 of pregnancy. The effects of a higher tar cigarette (tar 12.9 mg,
      nicotine 1.19 mg, carbon monoxide 9.01 mg/cigarette) and a modified brand (4.8,
      0.54 and 4.03 mg/cigarette respectively) were compared. Specific cells of the
      embryos were examined by scanning and transmission electron microscopy on day 9,
      20 hours after the last smoking episode. Cells of the neural plate, surface
      ectoderm, pericardium and heart all showed marked surface changes with the higher
      tar cigarettes which suggested depressed metabolic activity. The changes were
      sometimes less marked with lower tar cigarettes but not in all cell types.
      Transmission electron microscopy of the neural tube also showed that significant
      changes were associated with the higher tar cigarettes, particularly of the
      mitochondria which became elongate and the cristae more common and less distinct.
      These findings suggest that maternal smoking may cause anoxia in the embryo, and
      that the cellular changes this produces persist even 20 hours after smoking has
      ceased. However, cell counts of sections of the closed neural tube showed no
      change in the total cell number or number of dead cells or alteration in the
      mitotic index with either type of cigarette. Cigarette modification does reduce
      to some extent the detrimental effects of maternal smoking observed in the
      embryo, but it is by no means all-embracing.

PMID- 8871085
TI  - Cardiac ultrastructural effects of the platelet-activating factor and its
      antagonist BN 52021.
AB  - Platelet-activating factor-induced ultrastructural changes of myocardium were
      examined in isolated perfused guinea pig heart. The platelet-activating factor
      (10(-9)-10(7) M) caused the following electron microscopic changes: a) dilated
      capillaries filled with platelets and aggregated platelets. The endothelial cells
      adjoining the platelets remained uninjured but pericapillary oedema was observed.
      b) in the myocardium intracellular oedema, myofibrillar alterations, decrease of
      matrix density and rupture of crest in mitochondria can be seen. c) Ca2+ deposits
      in the cytoplasm increased and appeared in mitochondria, too. d) the
      intramitochondrially localised cytochromoxydase and succinic dehydrogenase
      activities were decreased. e) using lanthanum tracer permeability alterations
      were observed. Pretreatment with BN 52021 (10(6) M) completely prevented the
      morphological effects of the platelet-activating factor. From these results we
      conclude that the platelet-activating factor-induced vascular and ischemic like
      cellular damage appear to play an important role in the pathophysiology of
      myocardial ischemia.

PMID- 8871086
TI  - Unilateral renal ischemia reperfusion in the rat: effect of blood volume trapped
      in the kidney, sucrose infusion, and antioxidant treatments.
AB  - This study was carried out in order to examine whether the severity of acute
      renal failure observed during the four hours following a 45 min period of
      unilateral occlusion of the renal pedicle could be reduced by various treatments.
      These include intrarenal flush with saline immediately before the occlusion, by
      sucrose infusion immediately before reperfusion, or by injection of NAO (natural
      antioxidant) and vitamin E before the occlusion. After renal pedicle occlusion,
      creatinine levels increased to 165% of their pre-ischemic values. Urine flow,
      GFR, renal cortex blood flow and NADH decreased by 99%, 99%, 50% and 36%,
      respectively. A decrease in the Na and K reabsorption (15% and 32%, respectively)
      was also observed. Partial protection of renal function against ischemic damage
      was observed when kidney tissue remained blood-free, by exposing it to saline
      throughout the period of ischemia. Significant protection was observed after
      treatment with sucrose, vitamin E and NAO. This study demonstrates that it is
      possible to attenuate the injury to the ischemic kidney by inducing ischemia in a
      bloodless kidney, by inducing diuresis in the first phase of reperfusion, or by
      antioxidant treatment, such as vitamin E or NAO.

PMID- 8871087
TI  - The effect of quinolinic acid administered during pregnancy on the nigro-striatal
      complex of rat's offspring: ultrastructural investigation.
AB  - The nigro-striatal complex of rat's offspring was ultrastructurally examined
      after quinolinic acid administration to mothers during the gestation period, in
      order to mimick the congenital metabolic disturbances, resulting from an excess
      of quinolinic acid within foetal tissues. Hence, quinolinic acid was administered
      to mothers intraperitoneally in a dose of 60 mmol, once daily, throughout the
      entire gestation period. Brain specimens were taken on day 5 after birth, from
      experimental and control animals. Within the nigro-striatal complex there can be
      distinguished the more characteristic neuronal cell body alterations, and the
      more toxic effect as the edema signs and the retardment of the neuronal cell body
      maturity. In the substantia nigra, both swollen and dark-degenerated neuronal
      cell bodies have been identified, while in the striatum the latter forms
      predominated. The maturation of neuronal cell bodies was retarded, mainly within
      the striatum.

PMID- 8871088
TI  - Histopathology of subacute renal lesions in mice induced by streptozotocin.
AB  - Streptozotocin (SZ) was inoculated intraperitoneally to male and female mice of
      ICR and BALB/c strains in a different way of administration (A: single injection
      and B consecutive 5 days-injection) and subacute renal changes were examined
      light and electron microscopically 8 weeks after SZ-administration. The following
      changes were detected: (1) reduction in the rate of male-type Bowman's capsules
      in male mice, (2) karyocytomegaly of proximal tubular epithelial cells, and (3)
      dilation of distal tubules Tubular changes were detected with high incidence in A
      (males and females) and B groups (males) of ICR strain.

PMID- 8871089
TI  - Histopathological sequence of hepatic and renal lesions in rats after cessation
      of the repeated administration of CCl4.
AB  - The histopathological sequence of hepatorenal lesions in rats after cessation of
      the repeated administration of CCl4 (0.5 ml/kg, p.o., twice a week for 12 weeks)
      was examined. In the liver, cirrhotic lesions reduced rapidly after cessation of
      the CCl4-administration and collagen bundles surrounding the pseudolobules almost
      disappeared 12 weeks later. In contrast, in the kidney, vacuolation of epithelial
      cells in the proximal tubules disappeared rapidly but glomerular lesions
      progressed even after cessation of the CCl4-administration, and marked
      glomerulosclerosis developed 12 weeks later. Electron microscopically, marked
      expansion of the mesangial region due to increases of mesangial cells and matrix
      material, irregular thickening of the capillary basement membrane with mesangial
      interposition, and various degenerative changes in podocytes including deposition
      of small-sized droplets were observed.

PMID- 8871090
TI  - Histological and subcellular distribution of 65 and 70 kD heat shock proteins in
      experimental nephrotoxic injury.
AB  - The cellular distribution of 65 and 70 kD heat shock proteins (HSPs) was studied
      in the normal rat kidney and after acute tubular necrosis (ATN) induced by
      inorganic mercury (HgCl2). In the normal kidney the 65 kD HSP was found in the
      cytoplasm of podocytes and proximal convoluted tubules, whereas the 70 kD HSP was
      located in nuclei and cytoplasm of podocytes, cortical convoluted, and collecting
      tubules. The distribution of both HSPs along ATN changed as a function of time.
      In the early phase, before evidence of histological damage, both HSPs were found
      in the pielocaly ceal epithelium and medullary collecting tubules. During the
      necrotic phase, HSPs coexisted with sites of severe damage (i.e. cortical
      tubules). With immunoelectron microscopy damaged cells showed an abundance of 65
      kD HSP-I in mitochondria, as well as in chromatin and nucleoli, while 70 kD HSP-I
      was overexpressed in the cytoplasm, mito chondria, lysosomes, cytoskeleton,
      chromatin, and nucleoli, and coincided with urinary excretion of HSPs. In the
      postregenerative phase, the distribution of HSPs was similar to that found in the
      normal kidney. HSPs of 65 and 70 kD were encountered constitutionally and their
      immunolabeling is correlated with the magnitude of cell injury.

PMID- 8871091
TI  - Effects of fructose-induced hypertriglyceridemia on hepatorenal toxicity of
      acetaminophen in rats.
AB  - The mode of hepatorenal toxicity of acetaminophen (AAP) was compared between
      fructose-induced hyper-triglyceridemic and normal rats. The hypertriglyceridemic
      and normal rats received a single dose of AAP (0, 750 and 900 mg/kg ip) at week 5
      of fructose-treatment. At 24 hrs after AAP-dosing, they were sacrificed and
      examined blood biochemically and histopathologically. Hepatotoxicity as indicated
      by an increase in plasma ALT and AST activities and centrilobular necrosis of
      hepatocytes was more severe in the normal rats than in the hypertriglyceridemic
      ones. In contrast, nephrotoxicity as indicated by an increase in plasma urea
      nitrogen content and necrosis of epithelial cells in the proximal straight
      tubules was more severe in the hypertriglyceridemic rats than in normal ones.
      Thus, in the fructose-induced hypertriglyceridemic rats, as compared with normal
      ones, hepatotoxicity of AAP became apparently less severe, whereas nephrotoxicity
      of AAP became significantly more severe.

PMID- 8871092
TI  - Selective phototoxic destruction of quinacrine-loaded Merkel cells is neither
      selective nor complete.
AB  - Experiments were performed on slowly adapting type I mechanoreceptors in an
      isolated rat skin-nerve preparation (SA I receptors) and in an isolated rat sinus
      hair preparation (St I receptors). Merkel cells were stained in vitro with the
      fluorescent dye quinacrine and irradiated with ultraviolet (UV) light (2 mW for
      up to 1 h) while recording receptor responses to standard mechanical stimuli
      every 30 s. In addition, thresholds for electrically evoked action potentials
      were tested by applying electrical stimuli to the skin through the same stylus
      used for mechanical stimulation. UV irradiation resulted in abrupt failure to
      respond to mechanical stimuli in 73% of the SA I receptors examined (n = 37)
      within less than 1 h. This confirms previous reports of phototoxic destruction of
      Merkel cells. However, several minutes after the receptors failed to respond to
      mechanical stimulation, thresholds for electrical stimuli applied to the
      receptive field increased sharply. About 40% of the St I receptors (n = 13)
      irradiated with UV light following quinacrine staining stopped responding to
      bending of the hair within 1 h. In contrast, none of the seven St II receptors
      treated in the same way showed significant changes in the responses. Electron
      microscopic examination of sinus hairs after quinacrine staining alone showed
      slight changes in the appearance of Merkel cells, and in particular enlargement
      of the perinuclear space. These changes did not affect receptor responses.
      Electron microscopic studies of sinus hairs with receptors that had maintained
      normal responses to mechanical stimuli after quinacrine staining and 1 h of UV
      irradiation revealed that a substantial number of Merkel cells still had a normal
      ultrastructure while adjacent nerve terminals were severely swollen and partially
      compressing the Merkel cells. No changes were observed in lanceolate nerve
      terminals forming the morphological substrate of St II receptors. These results
      demonstrate that sensitivity to phototoxic destruction following quinacrine
      staining varies greatly among Merkel cells, with some maintaining normal function
      and ultrastructural appearance even after 1 h of UV irradiation. On the other
      hand there is clear evidence that the phototoxic damage affects the nerve
      terminals as well. Such experiments can therefore not provide conclusive proof
      about the role of Merkel cells in these mechanoreceptors.

PMID- 8871093
TI  - Increased oxidative metabolism in middle suprasylvian cortex following removal of
      areas 17 and 18 from newborn cats.
AB  - We measured changes in metabolic activity in middle suprasylvian (MS) cortex of
      cats subjected to early or late removal of areas 17 and 18 to localize shifts in
      activity possibly indicative of regions within MS cortex that may receive
      expanded inputs and be involved in the sparing of some visual behaviors following
      early primary visual cortex damage. Cytochrome oxidase (CO) activity was measured
      in MS cortex of mature, intact cats and of others with areas 17 and 18 removed in
      adulthood (P180), or on postnatal day 28 (P28) or postnatal day 1 (P1). Not less
      than 9 months after the ablation, brain sections were prepared and reacted for
      the presence of CO. The density of CO reactivity in each of the six cortical
      layers in MS cortex was measured and standardized against densities from ventral
      periaqueductal gray or hypothalamus on the same section. Following lesions on P1,
      significant increases in CO activity occurred in deep layer III and in layer IV
      of the medial bank of the MS sulcus, including all of area PMLS and the posterior
      portion of AMLS. In contrast, there were no significant differences in the level
      of CO activity among P28, P180, or intact cats for any of the cortical layers,
      and all had lower levels than the P1 cats. This metabolic change provides an
      anatomical marker for localizing adjustments in MS cortex and can be linked to
      amplified projections into MS cortex from the thalamus (LPm and A and C laminae
      of the dorsal lateral geniculate nucleus) and ventral posterior suprasylvian
      cortex following P1 ablations. Furthermore, this neurochemical analysis
      implicates a distinct region of MS cortex as the cortical locus of some spared
      visual functions following early primary visual cortex damage.

PMID- 8871094
TI  - The development of excitatory transmitter amino acid-containing neurons in the
      rat visual cortex. A light and electron microscopic immunocytochemical study.
AB  - The excitatory amino acids L-glutamate and L-aspartate are believed to be
      utilized as neurotransmitters by the pyramidal neurons in the mammalian cerebral
      cortex. These cells can be recognized early in development, while glutamate might
      play an important part in the maturation and plasticity of the cortex. Here, we
      used light and electron microscopic immunocytochemistry to study the time of
      appearance and maturation of glutamate and aspartate in neurons of the rat visual
      cortex. Glutamate- and aspartate-immunoreactive cells were first detected in deep
      cortical layers at postnatal day 3. During the next 3 weeks, labelled neurons
      were observed progressively in more superficial layers, but did not demonstrate
      their adult pattern of distribution until postnatal week 4. Electron microscopic
      analysis showed that glutamate- and aspartate-labelled neurons gradually develop
      their cytological and synaptic features during the first 4 postnatal weeks, with
      this process of differentiation originating in the deep cortical layers and
      progressively extending to the superficial layers. These findings suggest that
      cortical pyramidal neurons begin to express detectable levels of transmitter
      glutamate and/or aspartate after they have completed their migration. Their
      neurochemical differentiation follows an "inside-out" pattern similar to the
      pattern described for the genesis and morphological differentiation of this
      population of cortical neurons.

PMID- 8871095
TI  - Blockade of dopamine storage, but not of dopamine synthesis, prevents activation
      of a tolbutamide-sensitive K+ channel in the guinea-pig substantia nigra.
AB  - The substantia nigra has one of the highest levels of ATP-sensitive K+ channel in
      the brain. Since this channel is controlled by cell metabolism, the aim of this
      study was to see how closely it is associated with nigral dopamine systems, which
      are decreased in Parkinson's disease. In a sub-population of neurons within the
      rostral substantia nigra pars compacta of the guinea-pig, a brief period of
      hypoxia resulted in a tolbutamide (100-500 microM) sensitive hyperpolarisation
      [input resistance (IR) decrease from 144.88 +/- 14.04 M omega pre-hypoxia to
      105.91 +/- 13.25 M omega during hypoxia]. Maximal blockade of this decrease was
      seen in presence of 500 microns tolbutamide [IR decrease only from 161.35 +/-
      32.82 M omega to 155.02 +/- 34.29 M omega]. Reserpine (which depletes dopamine
      stores) but not alpha-methyl-para-tyrosine (which decreases de novo synthesis of
      dopamine) caused a marked attenuation of this hyperpolarisation [IR decrease only
      from 163.32 +/- 44.42 M omega pre-hypoxia to 154.42 +/- 50.97 M omega during
      hypoxia]. This observation suggests that blockade of dopamine storage, but not of
      de novo synthesis, leads to a loss of responsiveness of certain mid-brain neurons
      to hypoxia, rendering them potentially more susceptible to subsequent
      degeneration. The possible link between nigral dopamine systems and ATP-sensitive
      K+ channels is discussed.

PMID- 8871096
TI  - A light- and electron-microscopic study of GluR4-positive cells in cerebral
      cortex, subcortical white matter and corpus callosum of neonatal, immature and
      adult rats.
AB  - The distribution of the [3H]alpha-amino-3-hydroxy-5-methylisoxzalepropionic acid
      (AMPA) receptor subunit GluR4 was studied in frontal, parietal and temporal
      cerebral cortex, subcortical white matter and corpus callosum of neonatal,
      immature and mature rats. In 1- to 2-day-old rats, a few oligodendrocyte
      progenitors and amoeboid microglia in the supraventricular part of the corpus
      callosum were immunolabelled for GluR4. At 7 to 10 days, the number of amoeboid
      microglia and oligodendrocyte progenitors in white matter increased; many neurons
      in cortex, including pyramidal neurons, were also moderately labelled for GluR4.
      The pattern of GluR4 immunostaining in 14-day-old rats was different from that in
      7- to 10-day-old rats, but similar to the adult, in that there was no
      immunoreactivity in microglia and oligodendrocyte progenitors in subcortical
      white matter. A proportion of non-pyramidal neurons in cortex were moderately
      labelled, while some pyramidal neurons were lightly labelled. A population of
      small glial cells with features of oligodendrocyte progenitors were densely
      labelled in cortex.

PMID- 8871097
TI  - Neural connectivity only accounts for a small part of neural correlation in
      auditory cortex.
AB  - In order to allow the relation of functional connectivity patterns (inferred from
      cross-correlograms) to structural connectivity (the anatomical substrate), we
      analyzed cross-correlogram peaks for spontaneous and stimulated activity in the
      auditory cortex. It was assumed that the broad correlograms, usually encountered,
      represent neural connectivity as well as secondary effects such as intrinsic
      firing patterns, global synchrony related to the ongoing electroencephalographic
      activity, and stimulus-related effects. Data were collected from 604 neuron pairs
      recorded under spontaneous conditions in primary auditory cortex of seven
      juvenile (30-70 days) and nine adult cats. Three hundred and six pairs (51%) had
      a peak cross-correlation coefficient significantly different from zero. For 113
      neuron pairs out of this subgroup, correlations were calculated also for spike
      trains recorded during click stimulation. After a combined burst-correction and
      deconvolution procedure was carried out, the correlation peak strengths were not
      significantly changed for spontaneous activity, but peak width was narrower for
      single-electrode pairs than for dual-electrode pairs, suggesting a better
      synchronization for neighboring neurons. Under click stimulation conditions,
      overall peak synchronization strength was independent of interelectrode distance,
      whereas, after correction for secondary and stimulus effects, peak
      synchronization was significantly lower for dual-electrode pairs. However, the
      primary peak width for single-electrode pairs under stimulus conditions was no
      longer different from that of dual-electrode pairs. This implies that both under
      spontaneous and stimulus conditions secondary effects largely obscure any
      underlying correlation produced by anatomical connectivity. The secondary effects
      may be the result of intrinsic as well as network properties in auditory cortex
      and may functionally be more important than the weak primary effects resulting
      from anatomical connections. Cross-interval analysis suggests that the
      correlations in auditory cortex are dynamic and may show random switching between
      states of stronger and weaker synchronization.

PMID- 8871098
TI  - Effect of neck posture on patterns of activation of feline neck muscles during
      horizontal rotation.
AB  - The electromyographic (EMG) patterns of neck muscles were recorded during whole
      body horizontal rotation in head-free, alert cats and head-restrained,
      decerebrate cats. In some trials the cervical column of the animal was oriented
      vertically, whereas in others it was oriented more horizontally. In alert cats
      making head movements that compensated for the motion of the platform, neck
      muscles with modulated patterns of activity could be divided into a subset whose
      individual EMG patterns changed significantly when the neck posture was altered
      (including longissimus capitis, obliquus capitis superior and scalenus anterior)
      and a subset whose individual EMG patterns were invariant regardless of neck
      posture (including obliquus capitis inferior, levator scapulae and complexus). In
      head-restrained, decerebrate cats, electromyograms from all implanted muscles
      were modulated similarly in phase with the platform position. Changing the
      orientation of the neck had little effect upon these EMG patterns evoked by the
      horizontal vestibulocollic reflex. One decerebrate cat with strong extensor tone
      was tested further under head-free conditions. There was very little compensatory
      head movement, but individual neck muscles displayed patterns of activity that
      were more similar to those observed in alert, head-free animals.

PMID- 8871099
TI  - Accumulation of long-lasting inactivation in rat brain K(+)-channels.
AB  - We studied the phenomenon of cumulative inactivation in the voltage-dependent K+
      channels of the Shaker-related subfamily Kv1 cloned from rat brain and expressed
      in Xenopus oocytes. In Kv1.4, repetitive stimulations at intervals shorter than
      20 s produce cumulative inactivation even for brief stimuli that elicit K+
      currents which do not show any significant decline during the depolarising pulse.
      These effects are absent or greatly reduced in the clones Kv1.1, Kv1.3, Kv1.5 and
      Kv1.6, and in the deletion mutant Kv1.4-delta-110, characterised by lack of
      "fast" (N-type) inactivation. We find that the inactivation caused by a single
      pulse increases after the pulse while the channels deactivate, and subsides with
      two time constants, indicating the existence of (at least) two inactivated
      states: IS, with a slow recovery kinetics and IF, with faster kinetics. In the
      simplest kinetic scheme accounting for our observations, IF is coupled
      sequentially to the open state O, while IS can be reached at a fast rate both
      from IF and from a pre-open, activated state, A, that is in fast equilibrium with
      O. The accumulation of long-lasting inactivation during the repolarisation is
      favoured by the prolongation of the lifetime of activated states due to the
      presence of IF. This explains the smaller accumulation effect observed in
      channels lacking fast inactivation. The physiological implications of these
      findings suggest how different channels of the Kv1 subfamily can affect
      differently the firing behaviour of neurones.

PMID- 8871100
TI  - Firing properties of preposito-collicular neurones related to horizontal eye
      movements in the alert cat.
AB  - The projection from the nucleus prepositus hypoglossi (PH) to the superior
      colliculus (SC) has been proposed to provide a feedback control of collicular
      saccadic activities. The present study aimed to identify the functional
      properties of PH neurones projecting to the SC relative to eye movement
      parameters. Preposito-collicular neurones were identified in alert cats by
      antidromic invasion and collision tests following electrical stimulations of the
      contralateral SC. Their discharges were then correlated with the horizontal
      component of eye movements. Particular attention was given to the timing of
      discharges relative to saccade onsets. Most preposito-collicular neurones (12/14)
      displayed transient activities associated to eye velocity, and onsets preceded
      the saccade onset by 9.4-19.9 ms. The mean eye velocity sensitivity of these
      "early" preposito-collicular neurones (1.46 +/- 0.53 spikes/s per degree per
      second) was quite similar to that calculated from a sample of putative
      motoneurones or interneurones that have been recorded within abducens nucleus and
      quantified in the same conditions. The remaining two preposito-collicular
      neurones exhibited transient activity related to saccades, but this followed the
      transient putative motoneuronal discharge. These "delayed" neurones also had
      lower eye velocity sensitivities (0.38 sp/s per degree per second and 0.58 sp/s
      per degree per second, respectively) compared with early neurones. Both classes
      of preposito-collicular neurones also displayed a subsequent tonic activity
      correlated with the eye position. Taken together, these results demonstrate that
      preposito-collicular neurones code both eye position and eye velocity just like
      ocular motoneurones, but in a predictive manner. The anticipatory discharge of
      early neurones makes them likely candidates for the control of peak activities of
      saccade-related collicular neurones, particularly in the caudal colliculus.
      Delayed preposito-collicular neurones may also participate in the control of
      collicular activities, but probably in more rostral SC, where peak activities
      occur later during eye movements together with smaller motor error coding.

PMID- 8871101
TI  - Bicuculline-induced circling from the rat superior colliculus is blocked by GABA
      microinjection into the deep cerebellar nuclei.
AB  - In a recent electrophysiological experiment, we showed the deep cerebellar nuclei
      to be a major source of excitatory input to the superior colliculus. Furthermore,
      target neurons in the colliculus were found, in every case, to receive convergent
      tonic inhibitory input from the substantia nigra pars reticulata. In the present
      study, we investigated these effects in the awake rat. We asked whether circling
      behaviour, induced by unilateral injection of a GABA antagonist into the lateral
      colliculus, could be suppressed by concurrent cerebellar inactivation. Rats were
      chronically implanted with bilateral guide cannulae located above the superior
      colliculus and deep cerebellar nuclei. Bicuculline methiodide (25 pmol) was
      microinjected unilaterally into intermediate layers of the colliculus at
      increasing depths until an optimal contralateral circling response was elicited.
      This behaviour was taken as the "baseline response" and was the first of three
      treatments. The second was an identical manipulation of the colliculus with a
      concurrent 200-nl microinjection of 1 M GABA into the contralateral deep
      cerebellar nuclei. The third was a repeat of BIC alone into the colliculus or, if
      rotation had been suppressed by more than 50% on test 2, the treatment was
      collicular BIC plus deep cerebellar saline. This latter treatment was used as a
      control for possible non-pharmacological injection effects. The effect of
      cerebellar GABA at 26 sites (17 within cerebellar nuclei and 9 outside) on BIC
      induced rotation at 15 collicular sites was studied in ten animals. Only GABA
      injections at sites that fell within the cerebellar nuclei significantly reduced
      turning (P < 0.0001). A full behavioural analysis showed that this was a specific
      suppression of turning, not the result of general motor impairment. These results
      provide clear behavioral evidence that opposing, convergent influences from the
      basal ganglia and cerebellum interact in the lateral superior colliculus to
      control head and body movements. They furthermore suggest that the tonic deep
      cerebellar excitation of the superior colliculus could be the driving force in
      the expression of rotation induced by manipulations of the basal ganglia.

PMID- 8871102
TI  - Response properties of relay cells in the A-laminae of the cat's dorsal lateral
      geniculate nucleus after saccades.
AB  - Responses of relay cells in the A-laminae of the dorsal lateral geniculate
      nucleus (LGNd) during spontaneous saccades and saccade-like visual stimulation
      were extracellularly recorded in awake cats. Ninety-six out of 137 cells recorded
      (42 X and 54 Y cells) were responsive during spontaneous saccadic eye movements.
      All Y cells and 67% of the X cells responded with burst activity, i.e. with
      either one or two activity peaks during and after saccades. Thirty-three percent
      of the X cells were inhibited during saccades. Excitatory peaks occurred at mean
      latencies of 33 ms and 31 ms for X and Y cells, respectively. Comparable burst
      responses were obtained when retinal image shifts similar to those during
      saccades were induced by external saccade-like stimulus movements. However, the
      latencies of excitatory peak activity were significantly longer to external
      stimuli than to the onsets of saccades. This indicates the existence of an eye
      movement-related input which activates LGNd relay cells in addition to the visual
      input. We propose that the pretectogeniculate projection may contribute to the
      responses of LGNd relay cells following saccadic eye movements via a
      disinhibitory input and that this input could be involved in intra- and
      postsaccadic modulations of the transfer of visual signals to visual cortex.

PMID- 8871103
TI  - Auditory evoked fields to illusory sound source movements.
AB  - Auditory motion can be simulated by presenting binaural sounds with time-varying
      interaural intensity differences. We studied the human cortical response to both
      the direction and the rate of illusory motion by recording the auditory evoked
      magnetic fields with a 122-channel whole-head neuromagnetometer. The illusion of
      motion from left to right, right to left, and towards and away from the subject
      was produced by varying a 6-dB intensity difference between the two ears in the
      middle of a 600-ms tone. Both the onset and the intensity transition within the
      stimulus elicited clear responses in auditory cortices of both hemispheres, with
      the strongest responses occurring about 100 ms after the stimulus and transition
      onsets. The transition responses were significantly earlier and larger for fast
      than slow shifts and larger in the hemisphere contralateral to the increase in
      stimulus intensity for azimuthal shifts. Transition response amplitude varied
      with the direction of the simulated motion, suggesting that these responses are
      mediated by directionally selective cells in auditory cortex.

PMID- 8871104
TI  - Inter- and intra-limb coordination in arm tremor.
AB  - Inter- and intra-limb coordination in arm tremor was examined in adult subjects
      under vision and no vision conditions using accelerometery techniques. The
      accelerometer data were analyzed using standard time and frequency domain
      analyses and the regularity of the acceleration time series was determined using
      an approximate entropy (Ap En) measure. The data analysis was structured to
      examine the hypothesis that there is a functional compensatory relation between
      the motion (tremor) of the limb segments in the arm coordination postural
      pointing task. The results showed that the level of acceleration increased in a
      proximal to distal direction within a single arm and was symmetrical across
      homologous arm segments. The frequency analysis showed the established power
      spectral profiles for each limb segment in postural tremor tasks, but the finger
      motion included (beyond the normal 8-12 Hz and 20 Hz tremor) a third slower peak
      at around 2-3 Hz, due possibly to the reactive forces of the other arm links.
      There was no effect of vision on the level or frequency patterns of accleration
      in the limb segments. The coordination analysis showed that there was no linkage
      between the arms in either the time or frequency domain in the execution of this
      postural task. This result would tend to suggest that the neuronal commands
      underlying normal tremor are not derived from a common central oscillator within
      the central nervous system but are organized in a parallel fashion. The strength
      of the coupling of intra-limb coordination varied according to the particular
      adjacent limb links. There were significant correlations in the time domain and
      coherence in the frequency domain in the acceleration signals between upper arm
      and forearm, and between hand and finger. The phase lag of the arm units within
      each of these respective segment pairs was close to in phase or 0 deg.
      Significant coherence in the frequency domain was also evident between upper arm
      and hand motion, with the phase lag between these segments being close to 180 deg
      out of phase. The Ap En analysis of the acceleration signals revealed that there
      was more regularity to the upper arm and hand accelerometer signals than the
      forearm and finger signals. The findings show that the intra-limb coordination of
      the arm links in a two-limb postural pointing task is effected by a compensatory
      synergy organized about the action of the wrist and shoulder joints. This
      compensatory synergy reduces the coordination of the 4 within-limb degrees of
      freedom (arm links) to, in effect, a single degree of freedom arm control task
      that is not coupled in organization to the motion of the other limb or the torso.
      It is proposed that this coordination solution reduces the degrees of freedom
      independently regulated for realization of the task goal but preserves
      independent body segment control in critical degrees of freedom for potential
      adaptation to postural perturbations.

PMID- 8871105
TI  - Interaction of linear and angular vestibulo-ocular reflexes of human subjects in
      response to transient motion.
AB  - The possibility of synergistic interaction between the canal and otolith
      components of the horizontal vestibulo-ocular reflex (VOR) was evaluated in human
      subjects by subtracting the response to pure angular rotation (AVOR) from the
      response to combined angular and translational motion (ALVOR) and comparing this
      difference with the VOR to isolated linear motion (LVOR). Assessments were made
      with target fixation at 60 cm and in darkness. Linear stimuli were acceleration
      steps attaining 0.25 g in less than 80 ms. To elicit responses to combined
      translational and angular head movements, the subjects were seated on a Barany
      chair with the head displaced forwards 40 cm from the axis of rotation. The chair
      was accelerated at approximately 300 deg/s2 to 127 deg/s peak angular velocity,
      the tangential acceleration of the head being comparable with that of isolated
      translation. Estimates of the contribution of smooth pursuit to responses in the
      light were made from comparisons of isolated pursuit of similar target
      trajectories. In the dark the slow phase eye movements evoked by combined canal
      otolith stimuli were higher in magnitude by approximately a third than the sum of
      those produced by translation and rotation alone. In the light, the relative
      target displacement during isolated linear motion was similar to the difference
      in relative target displacements during eccentric and centred rotation. However,
      the gain of the translational component of compensatory eye movement during
      combined translational and angular motion was approximately unity, in contrast to
      the gain of the response to isolated linear motion, which was approximately a
      half. Pursuit performance was always poorer than target following during self
      motion. The LVOR responses in the light were greater than the sum of the LVOR
      responses in the dark with pursuit eye movements. We conclude that, in response
      to transient motion, there is a synergistic enhancement of the translational VOR
      with concurrent canal stimulation and that the enhancement of the LVOR in the
      light is not due solely to pursuit.

PMID- 8871106
TI  - Shift in saccadic direction induced in humans by proprioceptive manipulation: a
      comparison between memory-guided and visually guided saccades.
AB  - It is nowadays generally recognized that saccades to remembered targets are
      planned in a craniotopic frame of reference by combining retinal input with eye
      position signal. The origin of the eye position signal is still a matter of
      controversy, however. Does it arise from an efferent copy or is it supplied by
      the sensory receptors with which the extraocular muscles are endowed? When
      applied to skeletal muscles, vibration elicits spindle responses simulating a
      stretching of the vibrated muscle. When vibration is applied to the inferior
      rectus muscle (IR), it induces the illusion that a stationary fixating point is
      moving upward. Here we attempted to change the initial eye position signal
      supplied to the oculomotor system before a memory- or visuo-guided saccade to a
      10 degrees left target by applying mechanical vibration to the IR muscle. We
      wanted to determine whether modifying extraocular proprioceptive cues during the
      programming phase of a saccade might affect the latter's trajectory. In the
      memory-guided condition, it was observed that the saccades ended lower down when
      vibration was applied than in the control condition. Conversely, the visuo-guided
      saccades were not affected by the vibration. The above results mean first that
      extraocular proprioceptive cues are used as an initial eye position signal when a
      memory guided saccade has to be planned. Secondly, they suggest that extraocular
      proprioception may not be used to produce a visuo-guided saccade, or that this
      type of saccade is computed solely on the basis of retinal cues.

PMID- 8871107
TI  - A motor signal and "visual" size perception.
AB  - Recent models of the visual system in primates suggest that the mechanisms
      underlying visual perception and visuomotor control are implemented in separate
      functional streams in the cerebral cortex. However, a little-studied perceptual
      illusion demonstrates that a motor-related signal representing arm position can
      contribute to the visual perception of size. The illusion consists of an illusory
      size change in an afterimage of the hand when the hand is moved towards or away
      from the subject. The motor signal necessary for the illusion could be specified
      by feedforward and/or feedback sources (i.e. efference copy and/or
      proprioception/kinesthesis). We investigated the nature of this signal by
      measuring the illusion's magnitude when subjects moved their own arm (active
      condition, feedforward and feedback information available), and when arm movement
      was under the control of the experimenter (passive condition, feedback
      information available). Active and passive movements produced equivalent illusory
      size changes in the afterimages. However, the illusion was not obtained when an
      after-image of subject's hand was obtained prior to movement of the other hand
      from a very similar location in space. This evidence shows that
      proprioceptive/kinesthetic feedback was sufficient to drive the illusion and
      suggests that a specific three-dimensional registration of proprioceptive input
      and the initial afterimage is necessary for the illusion to occur.

PMID- 8871108
TI  - Effects of voluntary movements on early auditory brain responses.
AB  - It has not been clear whether or not early information processing in the human
      auditory cortex is altered by voluntary movements. We report a movement-related,
      complex event-related potential consisting of relatively long-lasting amplitude
      and phase perturbations induced in an ongoing auditory steady-state response
      (SSR) by brief self-paced finger movements. Our results suggest that processing
      in the auditory cortex during the first 50-100 ms after stimulus delivery is
      affected before, during, and after voluntary movements, beginning with a 1- to 2
      ms delay in the SSR wave form starting 1-2 s before the movement.

PMID- 8871109
TI  - Lipopolysaccharide induces apoptotic cell death of B memory cells and regulates B
      cell memory in antigen-nonspecific manner.
AB  - Lipopolysaccharide (LPS) was administered into sheep red blood cells (SRBC)
      primed mice, and the effect of LPS on SRBC-specific memory cells was
      investigated. Spleen cells from SRBC-primed mice which were injected with LPS
      exhibited much lower in vitro secondary plaque-forming cells (PFC) responses to
      SRBC than those from untreated SRBC-primed mice. The in vitro anti-SRBC response
      of the spleen cells to LPS was also reduced. The combination experiments of B
      cells and T cells from SRBC-primed mice which were injected with or without LPS
      demonstrated that the reduction of immune responses to SRBC after administration
      of LPS was caused by the defect of SRBC-specific B memory cells, but not T memory
      cells. B cell type rosette-forming cells (RFC) for SRBC markedly decreased after
      injection of LPS, while PFC as antibody-forming cells did not increase
      subsequently. Therefore, the reduction of RFC was not due to their
      differentiation into PFC. The lymphoid follicles in the spleens from mice
      injected with LPS were stained positively by in situ nick end labeling specific
      for fragmented DNA. A large percentage of Ig+ spleen cells from SRBC-primed mice
      which were injected with LPS was also stained positively. The injection of
      glucocorticoids into SRBC-primed mice induced similar reduction of B memory
      cells. It was suggested that LPS might induce apoptosis of B memory cells and
      regulate B cell memory in antigen-nonspecific manner.

PMID- 8871110
TI  - Lysophospholipase L2 of Vibrio cholerae O1 affects cholera toxin production.
AB  - The implication in cholera toxin (CT) production of the newly identified gene,
      lypA, that encodes the lysophospholipase L2 of Vibrio cholerae, was investigated.
      Introduction of lypA into the V. cholerae O1 mutant (NF404), which has a Tn5
      insertion in lypA and has lost CT as well as haemolysin production, restored the
      lysophospholipase activity and CT production but not the haemolytic activity.
      Inactivation of the lypA gene of the wild-type strain by chromosomal integration
      of a plasmid containing a portion of the lypA gene decreased the
      lysophospholipase L2 activity and the production of CT but not the haemolytic
      activity. Furthermore, constructed mutants of E1 Tor-biotype and Classical
      biotype strains which have a defective lypA failed to produce CT and exhibited
      decreased enterotoxicity in the ligated rabbit ileal loop test. These results
      suggest that lypA is possibly required for the expression of CT and may play a
      role in pathogenicity of V. cholerae.

PMID- 8871111
TI  - Repetitive and arbitrary primer DNA sequences in PCR-mediated fingerprinting of
      outbreak and sporadic isolates of Campylobacter jejuni.
AB  - PCR-mediated fingerprinting with combined repetitive and arbitrary DNA primers
      (ERIC-2 and 1026) was used to type Campylobacter jejuni from a milk-associated
      outbreak, and from sporadic cases of the same and allied HS serotypes. The 14
      outbreak strains had identical or similar DNA band profiles whereas the 25
      strains from sporadic infections were more heterogeneous with 18 different DNA
      profiles. Although PCR-based DNA fingerprints lacked serotype specificity, the
      method was fast, simple to perform and reproducible, provided defined technical
      protocols were adhered to precisely. Profiles were highly discriminatory but did
      not consistently match types based on other molecular methods. We conclude that
      AP-PCR has demonstrable potential for initial rapid investigation of outbreaks,
      and when used in conjunction with PFGE analysis of DNA restriction profiles,
      provides a high resolution strategy for accurately defining subtypes of C.
      jejuni.

PMID- 8871112
TI  - Identification and plasmid profiles of Lactobacillus species from the vagina of
      100 healthy women.
AB  - It was hypothesized that Lactobacillus acidophilus might not be the dominant
      aerobic or microaerophilic Lactobacillus species in the human vagina, and that
      the dominant isolates are likely to express a variety of properties associated
      with colonization. To examine the question, vaginal swabs were collected from 100
      healthy premenopausal women and cultured to detect the dominant aerobic or
      microaerophilic isolates of Lactobacillus. Only eight species were detected, with
      Lactobacillus jensenii being the dominant colonizers in the highest number (35)
      of women. Twelve different plasmid profiles were found amongst the isolates, but
      there was no association between plasmids and vaginal colonization or hydrogen
      peroxide production. Of the strains tested, few were resistant to the spermicidal
      agent nonoxynol-9. The data identify species within which strains may possess
      properties associated with maintenance of a healthy vaginal ecology.

PMID- 8871113
TI  - Macrophage release of tumor necrosis factor-alpha by Mycobacterium avium
      antigens.
AB  - Mycobacterium avium complex (MAC) infection is the most common disseminated
      opportunistic infection encountered in patients with AIDS. We have studied the
      ability of specific Mycobacterium avium (MA) antigen to stimulate human monocyte
      derived macrophages (MDM) to produce tumor necrosis factor-alpha (TNF-alpha). MDM
      stimulated with MA sonicate, MA 68 kDa and MA 48-52 kDa antigens were found to
      produce TNF-alpha in a dose-dependent manner. Reverse transcriptase-polymerase
      chain reaction analysis of mRNA extracts from antigen-stimulated MDM indicated
      that TNF-alpha mRNA expression was of brief duration and the time point of peak
      TNF-alpha mRNA levels was found to be antigen-specific. A significant difference
      in TNF-alpha production in response to MA 48-52 kDa antigen and M. bovis 65 kDa
      antigen was observed between MDM from normal and HIV positive individuals.

PMID- 8871114
TI  - Serum antibodies to commensal oral and gut bacteria vary with age.
AB  - This study examined the relationship between serum antibody levels to selected
      bacteria from the commensal oral and gut flora with increased age in a healthy
      adult population. A total of 116 healthy subjects were studied consisting of the
      following age groups: 20-39 years (group A), 40-59 years (group B), 60-79 years
      (group C) and 80+ years (group D). Only significantly lower mean IgM antibody
      levels to Streptococcus mutans strain Guy's serotype c were observed in older age
      groups (P < 0.001). With Actinomyces viscosus NCTC 10951 significantly reduced
      IgM levels (P < 0.02) and significantly elevated IgA levels were observed with
      increased age (P < 0.05). IgA and IgG antibodies to Escherichia coli NCTC 10418
      were increased significantly in the older age groups (P < 0.001), whilst a trend
      toward lower levels of IgM antibodies was recorded with age. No changes in IgA
      antibodies to Streptococcus faecalis NCTC 775 were observed but the lowest level
      of IgM antibodies were detected in the oldest age group (P < 0.05). Mean specific
      activity was decreased with age with IgM antibodies to the oral bacteria and
      increased with age with IgG and IgA antibodies to E. coli. Overall, our results
      suggest a general reduction in serum IgM antibody responses. This impairment in
      the circulatory IgM immune response may contribute to the increased occurrence of
      infections in the elderly.

PMID- 8871115
TI  - Biological characterization of Campylobacter fetus lipopolysaccharides.
AB  - Lipopolysaccharides (LPS) of three strains of Campylobacter fetus (subspp. fetus
      and venerealis, and serotypes A and B), a bacterium of veterinary importance but
      also a cause of various infections in humans, were assessed for their ability to
      induce mitogenicity, gelation of Limulus amebocyte lysate, lethal toxicity in
      mice, and pyrogenicity in rabbits. All C. fetus LPS exhibited activities lower
      than those of Salmonella typhimurium LPS. LPS of C. fetus subsp. fetus serotype A
      had the lowest activity in all assays. Since the majority of C. fetus subsp.
      fetus isolates from humans are serotype A, the lower biological activities of
      this LPS may aid the pathogenesis of such strains. The lower activities of C.
      fetus LPS compared with those of S. typhimurium LPS may reflect the presence of
      longer fatty acid chains in the lipid A of C. fetus LPS, whereas interstrain
      differences in C. fetus LPS bioactivities may be related to some property
      influenced by composition of the saccharide moiety.

PMID- 8871116
TI  - Porphyromonas gingivalis surface components induce interleukin-1 release and
      tyrosine phosphorylation in macrophages.
AB  - The aim of the present study was to characterize the responses of macrophages to
      surface antigens of Porphyromonas gingivalis. Native fimbriae, full-length
      recombinant fimbrillin, and a lectin-like 12-kDa antigen all stimulated BALB/c
      peritoneal macrophages to secrete interleukin (IL)-1 beta. The antigens induced
      similar patterns of tyrosine phosphorylation; proteins in approximately 35-46 kDa
      range of undetermined identities were phosphorylated in the macrophages. The
      abilities of the surface antigens to induce IL-1 beta were markedly attenuated by
      tyrosine kinase inhibitors. This inhibition correlated with inhibition of the
      induced phosphorylation of specific macrophage proteins at tyrosine. The data
      suggest that tyrosine kinase(s) plays an important role in the regulatory
      intracellular signaling mechanisms by which P. gingivalis surface antigens can
      mediate certain responses in macrophages.

PMID- 8871117
TI  - Probenecid, sulfinpyrazone and pyrazinamide do not inhibit urinary excretion of
      the beta 2-adrenoceptor agonist clenbuterol in cattle.
AB  - The objective of this study was to develop an analytical approach to determine
      whether the illegal application of clenbuterol in cattle as an anabolic agent can
      be concealed by co-treatment with substances that affect urinary excretion.
      Female veal calves were dosed orally with 0.8 microgram clenbuterol per kg of
      body weight twice daily for 28 days, as licensed for the therapeutic use which is
      registered in most European countries. On the eighth day of clenbuterol treatment
      each calf was additionally dosed orally either with probenecid, sulfinpyrazone or
      pyrazinamide at three different doses that were increased in weekly intervals.
      During the treatment blood and urine samples were obtained and analysed for
      clenbuterol by enzyme immunoassay and by high performance liquid chromatography/
      enzyme immunoassay to determine whether these drugs or their metabolites
      interfered with the immunological detection of clenbuterol. Clenbuterol could be
      in plasma (approximately 200 pg ml-1) and urine (1-40 ng ml-1) 5 h after the
      initial intake and throughout the whole treatment. None of the drugs reduced
      urinary excretion of clenbuterol to concentrations below the limit of detection.
      There was no prevention of clenbuterol detection in urine samples from calves
      that were co-treated with the drugs tested in this study. Our results demonstrate
      the uselessness of applying these drugs in order to conceal the illegal use of
      clenbuterol in meat production.

PMID- 8871118
TI  - Control and intake of pesticide residues during 1981-1993 in Finland.
AB  - The use of pesticides has been monitored on the basis of sales statistics since
      1953 in Finland and the information has been used for targeting the official food
      control to products where pesticides are mostly used. Food consumption and the
      earlier control results were also taken into account. The intake of pesticides
      has been estimated based on the control analysis and statistical food consumption
      data, where also the ratio of imports was taken into account. The samples were
      taken by food control authorities and analysed separately. In spite of slight
      bias owing to sampling for control purposes, the results are representative of
      the products consumed. The intake estimation method has been classified in the
      group Estimated Daily Intake (EDI). The intakes of a total of the 53 most
      commonly found pesticides were estimated. The intakes of the evaluated pesticides
      were below 2% of ADIs. The average daily intake was 75 micrograms per person in
      1992 mainly from imported products, only 24% initiating from domestic products.
      The intake of pesticides from domestic vegetables, fruits and berries has been
      evaluated three times during 1977-1993. The daily intake of pesticide residues
      from these products has decreased from 16.9 micrograms to 3.7 micrograms. The
      intensive food control has decreased offences against the regulations. The method
      used seems to be suitable for the longterm monitoring. The average intake of
      pesticides is at a low level compared with the Acceptable Daily Intakes, thus
      further estimations by more defined methods are not necessarily needed. The
      advantage of the method adopted is that residue data can also be used to make
      more accurate Measured Daily Intake estimates for risk groups such as children
      and vegetarians.

PMID- 8871119
TI  - Screening method for the gas chromatographic/mass spectrometric determination of
      microgram/litre levels of bromate in bottled water.
AB  - Bromate can be formed as a by-product of ozone treatment that is sometimes used
      for the disinfection of municipal water supplies and bottled waters. The US
      Environmental Protection Agency has proposed a maximum contaminant level (MCL) of
      10 micrograms/l for bromate in public drinking water. Should the proposed MCL for
      bromate become final, it may then be considered for adoption as a bottled water
      quality standard by the US Food and Drug Administration. This paper reports the
      development of a gas chromatographic/ mass spectrometric (GC/MS) method for the
      determination of parts-per-billion (microgram/l) levels of bromate (BrO3-) in
      bottled water. The GC/MS method was validated by using distilled and deionized
      Milli-Q water; detection limits, quantitation limits, and recoveries were
      determined and identities were confirmed by MS on the basis of analyses of test
      portions fortified with BrO3- at 0.8, 3.8, 7.7, 15, and 46 micrograms/l. The
      method also was evaluated on the basis of recoveries determined for two
      commercial brands of bottled water fortified with BrO3- at 3.8 and 7.7
      micrograms/l and two commercial brands fortified at 0.8, 3.8, and 7.7
      micrograms/l. For the Milli-Q water, recoveries ranged from 100 to 121%; for the
      fortified commercial products, recoveries ranged from 87 to 115%. The limits of
      detection and quantitation were determined to be 0.4 and 0.7 microgram/l,
      respectively. Several commercial brands of bottled water were analysed, and BrO3-
      was found in these products at levels ranging from none to 38 micrograms/l.

PMID- 8871120
TI  - Measurement of bromate in bottled water by high-performance liquid chromatography
      with post-column flow reactor detection.
AB  - The objective of this work was to develop a reliable, rugged high-performance
      liquid chromatographic (HPLC) method for determination of trace levels of bromate
      (< 10 micrograms/l) in bottled water. HPLC separation was achieved by ion
      interaction chromatography using a C-18 reversed-phase column and a mobile phase
      consisting of methanol/water (20:80, v/v) with tetrabutylammonium acetate as the
      ion interaction reagent. A post-column reaction based on oxidation of o
      dianisidine in acidic solution to a product detected at 500 nm provided selective
      measurement of the oxidants. The limit of detection and the limit of quantitation
      were 1 and 3 micrograms/l, respectively. Iodate, chlorite, and nitrite were
      chromatographically separated from bromate and measured by monitoring the post
      column reaction. Chloride and chlorate at levels that might be found in bottled
      water did not interfere with the determination of bromate. Bromate was detected
      in bottled waters at concentrations up to 40 micrograms/l.

PMID- 8871121
TI  - Benzo(a)pyrene in Brazilian vegetable oils.
AB  - Samples of vegetable oils on the Brazilian market including rape seed, corn,
      soybean, sunflower, rice, palm and garlic were analysed for benzo(a)pyrene
      (B(a)P). The analytical method involved liquid-liquid extraction, clean-up on
      silica gel column and determination by high performance liquid chromatography
      using fluorescence detection. The limit of detection was 0.5 microgram/kg.
      Benzo(a)pyrene was detected in almost all samples, at levels up to 58.9
      micrograms/kg. The mean levels of B(a)P in rice, sunflower, soybean, corn and
      palm oils were 1.8, 0.2, 2.2, 10.8 and 2.1 micrograms/kg respectively. No B(a)P
      was detected in garlic and rape seed oils. The data indicate that the levels of
      B(a)P found in Brazilian corn oils are relatively higher than those published in
      the literature for European corn oils.

PMID- 8871122
TI  - Contents of lead and cadmium in selected fish species consumed in Finland in 1993
      1994.
AB  - The lead and cadmium contents of the main fish species consumed in Finland were
      determined by ETAAS after wet digestion with HNO3. Analytical quality was
      controlled with blanks, reference materials and blind replicates. Mean and median
      lead contents of domestic fish species were < LOD (1 microgram/kg)-9.4
      micrograms/kg and < LOD-4.7 micrograms/kg. The lead contents of imported fish and
      imported canned or salted fish ranged from < LOD to 8, and 4 to 177
      micrograms/kg. Mean and median cadmium contents of domestic fish species were <
      LOD (0.4 microgram/kg)-5.8 micrograms/kg and < LOD-4.4 micrograms/kg Fresh
      imported fish contained < LOD-11 micrograms Cd per kg and canned or salted fish 9
      42 micrograms Cd per kg. Higher fish consumption would not increase lead or
      cadmium intake significantly in Finland. At present fish contributes about 4% of
      the average lead intake and 3% of cadmium intake.

PMID- 8871123
TI  - Ochratoxin A in table wine and grape-juice: occurrence and risk assessment.
AB  - The concentrations of ochratoxin A (OA) and C (ethyl ester of OA, OC) have been
      measured in table wine from the Swiss retail market. The overall median
      concentrations of OA in white, rose and red table wine were (number of samples;
      range) < 3 pg/ml (24; < 3-178 pg/ml), 19 pg/ml (15; < 3-123 pg/ml) and 13 pg/ml
      (79; < 3-388 pg/ml)), respectively. For dessert wines (Malaga, Marsala) a median
      of 337 pg/ml (5; 44-451 pg/ml) resulted. Concentrations of OC were about 10% of
      those of OA. OA has been detected in red grape-juices for the first time with
      median concentrations amounting to 235 pg/ml (8; < 3-311 pg/ml). White grape
      juices (3) as well as other fruit juices (2 apple, 6 orange, 2 others) did not
      contain OA (< 5 pg/ml). The analytical method used was not appropriate for
      grapefruit-juices because of an interfering substance. The results indicate that
      OA is formed prior to the alcoholic fermentation. It also appears that the more
      southerly in Europe is the origin of the samples the higher is the frequency of
      occurrence and the concentration of OA in red wines and red grape-juices.
      Although the estimated mean daily OA intake of 0-7 ng/kg body mass (men) can
      easily be more than doubled by moderate wine consumption, an additional health
      risk by OA is not to be expected. On the other hand the consumption of red grape
      juices among infants and children may result in intakes high enough to justify a
      reduction of the OA concentrations in these juices to less than 100 pg/ml.

PMID- 8871124
TI  - Determination of ochratoxin A in regional samples of cow's milk from Germany.
AB  - Samples (121) of cow's milk from a northern region of Germany were analysed for
      the occurrence of ochratoxin A by means of a sensitive high-performance liquid
      chromatographic (HPLC) method. The samples were extracted with a mixture of
      chloroform and methanol at pH < 2. The extracts were cleaned up by solid-phase
      extraction on silica gel cartridges. The detection limit was 0.01 ng/ml, the
      quantitation limit was estimated at 0.03 ng/ml. The mean recovery from spiked
      samples was 84 +/- 7% in the concentration range of 0.03-0.5 ng/ml. An enzyme
      linked immunosorbent-assay (ELISA) was shown to be suitable for the confirmation
      of ochratoxin A levels down to the detection limit of the HPLC method. No
      ochratoxin A was detected in the samples analysed, either by HPLC or by ELISA.

PMID- 8871125
TI  - Co-production of aflatoxins and cyclopiazonic acid in isolates of Aspergillus
      flavus.
AB  - The distribution of total aflatoxin (AFT) and cyclopiazonic acid (CPA) between
      conidia and mycelial matrix was studied in five isolates of Aspergillus flavus
      Link cultured on maize grain for 20 days at 30 degrees C. Total aflatoxin and CPA
      production differed between the isolates with Aspergillus flavus F2R4FP 1-5
      producing the most AFT (conidia-0.245 microgram/g; mycelial matrix-83
      micrograms/g) and CPA (conidia-0.091 microgram/g; mycelial matrix-37
      micrograms/g). The production of AFT and CPA by this isolate was compared in
      liquid (malt-extract-yeast-extract-glucose) and solid substrates (yeast extract
      sucrose agar and maize) at 30 degrees C. The ratio of AFT:CPA in maize decreased
      from 16.6:1 to 1.6:1 between 7 and 21 days' incubation. In liquid culture and
      yeast extract sucrose agar, the ratios were reversed and ranged from 1:3 to 1:9
      and 1:22 to 1:28, respectively, the greatest difference in both media occurring
      after 15 days.

PMID- 8871126
TI  - Determination of methamidophos residues in food remnants.
AB  - Over the past 7 years, acute food poisoning arising from the consumption of
      methamidophos-tainted vegetables has occurred sporadically in Hong Kong. To
      enable prompt remedial and regulatory actions to be taken, a simple and rapid gas
      chromatographic method was developed to determine methamidophos residues in food
      remnants. Samples were homogenized and extracted with acetone. Acetone in the
      resultant extract was removed by rotary evaporation, leaving behind an aqueous
      solution. After washing with petroleum ether and addition of sodium sulphate, the
      aqueous solution was re-extracted with chloroform. The chloroform extract was
      concentrated to dryness and the residue was reconstituted in absolute ethanol for
      determination by gas chromatography with flame photometric detection. The method
      was found to be applicable also to the determination of acephate, dimethoate,
      omethoate and trichlorfon. Mean recoveries of the five organo-phosphorus
      pesticides at two fortification levels, viz. 1 mg/kg and 10 mg/kg, ranged from 74
      to 113%. Relative standard deviations lay between 1.3 and 6.1%. Method detection
      limits ranged from 0.02 to 0.04 mg/kg. In 1994, 75 food poisoning cases in Hong
      Kong were suspected to be related to the consumption of methamidophos-tainted
      vegetables; 13 food remnants were received for analysis, four of them were found
      to contain high concentrations of methamidophos.

PMID- 8871127
TI  - Cyclamate consumption in Catalonia, Spain (1992): relationship with the body mass
      index.
AB  - The dietary intake of cyclamate was evaluated in the north-east of Spain in 1992.
      In a random sample of the Catalan population consisting of 2450 people aged 6-75
      years, two 24-h recalls at different seasons were collected; the amount and type
      of all foods, drinks and drugs consumed were obtained and the total daily intake
      of cyclamate was expressed in mg/kg body weight (bw), as the average of both 24-h
      recalls. Eighteen percent of the population consumed cyclamate, and the highest
      percentage was in men aged 35-44 years (33%). Average daily intake of cyclamate
      was 0.44 mg/kg bw in the whole population and 2.44 mg/kg bw among consumers.
      Subjects following a diet reported highest intakes, especially diabetics, and
      only 0.16% of the sample studied had levels above the Acceptable Daily Intake
      (ADI). Among consumers, the intake of cyclamate was negatively correlated with
      Body Mass Index (BMI). The results show the pattern of cyclamate intake in the
      Spanish population.

PMID- 8871128
TI  - Determination of low nanogram/millilitre levels of volatile organic compounds in
      on-purpose and by-product hydrochloric acids.
AB  - Hydrochloric acid (HCl) is used in the food industry as a processing aid in the
      manufacture of certain foods. HCl is manufactured, either directly from inorganic
      sources, i.e. "on-purpose' or indirectly as a by-product from the production of
      organic compounds generally intended for non-food applications. By-product HCl
      potentially may contain traces of the manufactured product, its precursors, and
      other reaction by-products. Many of the potential contaminants are volatile
      organic compounds (VOCs) such as vinyl chloride and benzene. A study was
      conducted to determine whether there were differences between the levels of VOCs
      found in HCl samples collected from two on-purpose HCl manufacturers and two by
      product HCl manufacturers. Process water used to manufacture the HCl also was
      analysed. Twenty-nine VOCs were determined by purge- and-trap concentration and
      capillary gas chromatography/mass spectrometry. Of these, nine were found in the
      process water and in both the by-product and on-purpose HCl samples at total VOC
      levels of less than 116 ng/ml. The levels of total VOCs identified in the two on
      purpose HCl samples were 58 and 80 ng/ml; the levels of total VOCs identified in
      the two by-product samples were 41 and 115 ng/ml. The process water appeared to
      be the source of most of the contaminants. These results show that the levels of
      VOCs found in the two types of acid are comparable.

PMID- 8871129
TI  - Migration from plasticized poly(vinyl chloride) into fatty media: importance of
      simulant selectivity for the choice of volatile fatty simulants.
AB  - An investigation was carried out to determine whether isooctane and ethanol
      behave like sunflower oil as fatty simulants for overall and for specific
      migration from PVC containing aromatic plasticizers (bis-2-ethylhexyl phthalate
      and tris-2-ethylhexyl trimellitate). In these films, the partition coefficients
      of migrants between simulant and polymer play a major role. The affinities of
      isooctane and of sunflower oil to all migrants were similar and isooctane can be
      considered as an alternative fatty simulant for plastized PVC. In contrast
      ethanol displays a different selectivity, and is not an adequate fatty simulant.
      Guidelines for the selection of solvents to be used as fatty simulants for
      migration testing are discussed. The scope of spectroscopic methods (FTIR and 1H
      NMR) to monitor migration of aromatic plasticizers is presented.

PMID- 8871130
TI  - Electrophysiology of ion channels of the heart.
AB  - The contribution of Na+, Ca2+, and various K+ currents to the shape of the
      cardiac action potential is outlined based on the relation between
      electrophysiological properties and structure of channel molecules. These
      currents have also been found in human ventricular myocytes, where the most
      prominent K+ current is a transient outward current that is not influenced by
      methylsulfonanilide antiarrhythmic drugs. Combined knowledge of
      electrophysiological and molecular properties of ion channels is likely to form
      the basis for rational design of future drugs.

PMID- 8871131
TI  - Pharmacodynamic behaviour of isolated resistance vessels obtained from
      hypertensive-diabetic rats.
AB  - The influence of various vasodilator and constrictor drugs was studied in
      isolated mesenteric arteries obtained from obese and lean Zucker rats. The obese
      Zucker rats were moderately hypertensive and their isolated small arteries were
      not hypertrophied. All vasoconstrictor agents studied (noradrenaline,
      methoxamine, serotonin, calcium chloride, potassium chloride) caused the same
      effects in isolated arteries taken from obese and lean (control) Zucker rats;
      respectively. In vessels from obese Zucker rats, the vasodilator responses to
      sodium nitroprusside, methacholine, the K(+)-channel opener cromakalim and
      nifedipine were the same as in control preparations. In conclusion, isolated
      mesenteric arteries from obese Zucker rats do not show relevant structural
      changes, and the pharmacodynamic behaviour of such vessels appears to be the same
      as that of control preparations. Neither the diabetic hyperinsulinaemic state not
      the hyperlipoproteinaemia in the obese Zucker rats appear to cause serious
      vascular damage.

PMID- 8871132
TI  - Pharmacological evidence that NK-2 tachykinin receptors mediate hypotension in
      the guinea pig but not in the rat.
AB  - Vascular NK-1 and NK-2 tachykinin receptors in the rat and the guinea pig were
      characterized pharmacologically by using available agonists and antagonists
      exhibiting varying degrees of selectivity for these receptors. Because the
      anesthetized guinea pig has unusually low blood pressure, these animals were
      pithed and vagotomized and infused, throughout the experimental procedure, with
      norepinephrine (6 micrograms/kg/min). This treatment raised their blood pressure
      to a level appropriate for the determination of dose-hypotensive response curves.
      The NK-1 receptor agonists substance P (SP) and septide (0.004 to 1 microgram/kg
      iv) decreased carotid artery blood pressure in a dose-dependent manner in both
      species, but they were more potent (13- and 33-fold, respectively) in guinea pigs
      than in rats. The NK-2 receptor agonist [beta Ala8]-NKA(4-10) (0.06 to 1
      microgram/kg) also dose-dependently lowered blood pressure in the pithed guinea
      pig with noradrenaline-supported blood pressure, although it failed to do so in
      the same rat preparation. RP 67580, a selective NK-1 antagonist, antagonized the
      SP- or septide-induced hypotensive response in rats, but not in guinea pigs.
      Conversely, RPR 100893, a novel NK-1 receptor antagonist chemically related to RP
      67580, dose-dependently inhibited hypotension induced by SP, and even more, that
      induced by septide only in guinea pigs. In the latter species, neither RP 67580
      nor RPR 100893 affected decreases in blood pressure induced by [beta Ala8]-NKA(4
      10). These decreases were, however, inhibited by the NK-2 receptor antagonist SR
      48968. The selectivity of this compound for the latter receptor was confirmed by
      its failure to affect SP- or septide-induced hypotension in either guinea pigs or
      rats. These results confirm that the hypotensive responses to SP and septide are
      mediated by NK-1 receptors in the two species studied. However, functional NK-2
      receptors appear to be present in the vascular bed of the guinea pig but not that
      of the rat, since in the former species the hypotensive responses induced [beta
      Ala8]-NKA(4-10) were inhibited by SR 48968 but not by the NK-1 receptor
      antagonists studied. This conclusion is, to our knowledge, drawn here for the
      first time from clear-cut pharmacological results.

PMID- 8871133
TI  - NMDA antagonist blockade of AT8 tau immunoreactive changes in neuronal cultures.
AB  - Antagonists at four distinct regulatory sites on the N-methyl-D-aspartate (NMDA)
      receptor were tested for their ability to attenuate NMDA-mediated chronic
      excitotoxicity and the consequences on AT8 tau immunoreactivity in neuronal
      cultures. Excitotoxicity was monitored in cultures by diacetate fluorescein
      staining. Immunoreactivity of tau phosphorylated at serine 202 was quantified by
      laser confocal microscopy. The NMDA-receptor antagonists MK801, AP7 and 7
      chlorokynurenate significantly blocked NMDA-induced cell death and significantly
      reduced AT8 tau immunoreactivity. NMDA antagonism by the polyamine site
      antagonist, ifenprodil, did not completely reverse the increase in AT8 tau
      immunolabeling induced by NMDA and did not completely protect NMDA-sensitive
      neurons, suggesting an heterogeneity in the NMDA receptor population.

PMID- 8871134
TI  - Circadian phase dependent pharmacokinetics of L-dopa, its main metabolites (3
      OMD, HVA, DOPAC) and carbidopa in rats.
AB  - This study aims to evaluate whether or not the kinetics of L-dopa, its main
      metabolites (3-O-methyldopa, 3-OMD, homovanilic acid, HVA and 3,4
      dihydroxyphenylacetic acid, DOPAC) and carbidopa, vary according to the 24-hour
      scale in rats. Four groups of seven adult male Wistar AF EOPS rats were used for
      these experiments; each group received L-dopa (200 mg.kg-1 ip) and carbidopa (20
      mg.kg-1 ip) at 1000, 1600, 2200 or 0400 hours. L-dopa, 3-OMD, DOPAC, HVA and
      carbidopa were simultaneously determined by specific ion-pair reversed-phase high
      performance liquid chromatography with electrochemical detection. A temporal
      variation of the kinetics of both L-dopa and carbidopa was demonstrated with
      higher plasma clearance and lower area under concentration curve after the
      administration at 2200 hours. Moreover, a temporal variation of the metabolism of
      L-dopa was indirectly documented by temporal variation in kinetics of 3-OMD,
      DOPAC and HVA.

PMID- 8871135
TI  - Salbutamol potentiates the relaxant effects of selective phosphodiesterase
      inhibitors on guinea pig isolated trachea.
AB  - The ability of low concentrations of salbutamol to potentiate the relaxant
      effects of the phosphodiesterase (PDE) inhibitors, rolipram, Ro 20-1724 (PDE type
      IV inhibitor), siguazodan and milrinone (PDE type III inhibitor) was studied on
      guinea pig isolated trachea. These PDE inhibitors were strong relaxants of guinea
      pig trachealis under basal tone, but had only a weak activity on tissues
      precontracted with histamine (10(-5) M). In both cases, PDE type IV inhibitors
      showed a relaxant effect composed of two phases. The first phase represented 20
      and 40% and the second, 90 and 140%, respectively, of relaxation of basal tone
      and histamine-induced tone. A second characteristic of PDE type IV inhibitors was
      the very fast and partially reversible relaxation observed at concentrations
      greater than 3 x 10(-8) M (for histamine-induced tone) at the first addition of
      inhibitor, followed by a residual relaxant activity. The latter relaxant effect
      was stable at concentrations of 3 x 10(-8)-10(-5) M and was equivalent to a 20%
      relaxation (for histamine-induced tone). In the presence of low concentrations
      (10(-9) and 10(-8) M) of salbutamol, there was a significant concentration
      dependent potentiation of the effects of PDE inhibitors on trachea precontracted
      with histamine. Salbutamol, at a concentration of 10(-9) M, potentiated the
      effects of PDE inhibitors between 1.4- and 3.6-fold. In the presence of
      salbutamol 10(-8) M, the potentiation was more marked for siguazodan (37.9-fold),
      milrinone (11.0-fold) and Ro 20-1724 (14.5-fold) than for rolipram (4.3-fold).
      These results suggest that low concentrations of salbutamol can potentiate the
      relaxant effects of both PDE type III and PDE type IV inhibitors. Thus, PDE type
      IV inhibitors, which have antiinflammatory properties, could also provide
      adequate bronchodilation when used in combination with lower than usual doses of
      beta 2-agonists.

PMID- 8871136
TI  - Effects of SCA40 on human bronchi and on guinea pig main bronchi in vitro.
      Comparison with cromakalim.
AB  - The aim of this study was to examine the activity of SCA40, a novel charybdotoxin
      sensitive potassium channel opener, against a variety of spasmogens or against
      electrical field stimulation in guinea pig isolated main bronchi and in human
      isolated bronchi; the effects of SCA40 were compared with those of cromakalim.
      Like cromakalim, SCA40 reduced the contractility of guinea pig and human isolated
      bronchi precontracted with acetylcholine 10(-6) M or neurokinin A 10(-6) M, SCA40
      being more efficient and more potent than cromakalim. Moreover, on guinea pig
      isolated main bronchi, SCA40 can exert a preventive effect on contractions
      induced by acetylcholine, neurokinin A or capsaicin, that is, it shifts to the
      right the concentration-effect curves of these substances, whereas cromakalim has
      no such effect. The effects of cromakalim were antagonized by glibenclamide 10(
      5) M, whereas the effects of SCA40 were inhibited by tetraethylammonium (TEA 10(
      2) M) and charybdotoxin (3 x 10(-8) M), but this inhibitory effect of TEA was
      reversed by nifedipine (10(-6) M). Electrical field stimulation of guinea pig
      isolated main bronchi induced two successive contractile responses. Both
      contractions were significantly reduced by SCA40 (10(-6) and 10(-5) M) and
      cromakalim (10(-5) M). Since cromakalim was unable to inhibit the effects of
      acetylcholine or neurokinin A, it might be suggested that for this latter
      compound the inhibition seems to take place prejunctionally and to affect the
      release of neuromediators produced by electrical field stimulation. In contrast,
      in the case of SCA40, a postjunctional effect seems to be likely, owing to its
      preventive effects, although a prejunctional effect cannot be excluded. Finally,
      on guinea pig isolated main bronchi, SCA40 (10(-8)-10(-6) M) did not potentiate
      the relaxant effect of isoprenaline or sodium nitroprusside, suggesting a lack of
      functional manifestation of inhibition of phosphodiesterase for these
      concentrations. In conclusion, these results demonstrate that SCA40 is a potent
      and efficient relaxant of guinea pig and human airway smooth muscle, and is able
      to inhibit, in the guinea pig isolated main bronchi, the contractions induced by
      electrical field stimulation. It has an effect on TEA-sensitive K+ channels, but
      this effect is probably not involved in its relaxant effect which does not also
      rest on an inhibitory effect of phosphodiesterase.

PMID- 8871137
TI  - Rilmenidine activates postjunctional alpha 1- and alpha 2-adrenoceptors in the
      canine saphenous vein.
AB  - Experiments were performed to determine the subtypes of alpha-adrenoceptors
      involved in the contraction induced by rilmenidine in isolated canine cutaneous
      veins. Rings of saphenous vein (without endothelium) were suspended for the
      recording of isometric force in physiological salt solution. All experiments were
      performed in the presence of propranolol (to antagonize beta-adrenoceptors),
      cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal
      uptake). In the presence of rauwolscine (an alpha 2-adrenergic blocker),
      rilmenidine caused concentration-dependent contractions which were inhibited by
      prazosin (nonselective alpha 1-antagonist) and by (+)niguldipine (selective alpha
      1A-adrenergic antagonist), but not by (-)niguldipine. After treatment with
      phenoxybenzamine (to alkylate alpha 1-adrenoceptors), rilmenidine evoked
      contractions of the canine saphenous vein which were antagonized competitively by
      rauwolscine. The combination of rauwolscine and prazosin did not abolish
      contractions evoked by the highest concentrations of rilmenidine. Although
      binding experiments using 3H-idazoxan suggested the existence of a nonadrenergic
      binding site (around 20% of the total binding), contractile studies failed to
      demonstrate their involvement in the increases in tension evoked by rilmenidine.
      These experiments suggest that the contractions evoked by rilmenidine in isolated
      canine veins are mediated by both alpha 1A- and alpha 2-adrenoceptors.

PMID- 8871138
TI  - A randomized, double-blind, multicentre controlled trial of ibuprofen versus
      acetaminophen and placebo for symptoms of acute otitis media in children.
AB  - Two hundred and nineteen children (boys: 56%, girls: 44%) were included in a
      randomized, double-blind, multicentre (4 centres) controlled trial designed to
      assess the efficacy and safety of ibuprofen (IBU) in the treatment of 1 to 6 year
      old children with otoscopically proven acute otitis media (AOM), either
      unilateral or bilateral. They randomly received 10 mg/kg IBU (n = 71), or
      acetaminophen (PARA) (n = 73) or placebo (PLA) (n = 75), orally, tid, for 48
      hours. All received oral cefaclor (Alfatil, Lilly, France) for seven days. They
      were evaluated before (D0) and at the end of treatment (D2). The main criterion
      of response was the aspect (landmarks and color) of the tympanic membrane
      assessed on a semi-quantitative scale from 0 to 6. Other criteria, assessed on
      semi-quantitative scales, included relief of pain (0 or 1), rectal temperature (0
      to 2), and overall evaluation by parents of the improvement of quality of life on
      three items: appetite (0 to 2), sleep (0 to 2), and playing activity (0 to 2).
      The results at D2 were as follows: there was no significant difference between
      treatment groups as to the main criterion, but only a trend for IBU and PARA to
      do better than PLA but not for IBU to do better than PARA. From these data there
      is no argument to emphasize the utility of non-steroidal anti-inflammatory drugs
      (NSAIDs) in treating the inflammatory signs of the tympanic membrane in otitis.
      There was a statistically significant difference between treatment groups at D2
      for pain, IBU being superior to PLA (P < 0.01): 7%, 10% and 25% of the children
      were still suffering at D2 in the IBU, PARA and PLA treatment groups,
      respectively. The difference between PARA and PLA for pain was not statistically
      significant. There was no significant difference between treatment groups for the
      other criteria. All treatments were well and equally tolerated. Although no
      significant difference was found between the treatment groups on the aspect of
      the tympanic membrane, the efficacy of IBU was evidenced on the relief of pain,
      the symptom that most disturbs the child.

PMID- 8871139
TI  - Blood flow acceleration in the carotid and brachial arteries of healthy
      volunteers: respective contributions of cardiac performance and local resistance.
AB  - The influence of local resistance and cardiac performance on peripheral blood
      acceleration was investigated in 14 healthy male volunteers. Steady and pulsatile
      flow was studied in the brachial and in the common carotid arteries, ie, two
      territories that exhibit marked differences in resistive characteristics.
      Instantaneous blood velocity (V), mean blood velocity (Vm) and artery diameter
      (D) were evaluated at rest by an ultrasonic range-gated pulsed Doppler flowmeter
      using a double transducer probe, thus allowing the calculation of mean blood flow
      (Q). Mean local resistance (R) was obtained by dividing the mean arterial
      pressure by Q. The peak value of the local acceleration of the blood was obtained
      by computer-assisted calculation of the first derivative of instantaneous blood
      velocity (Gmax = +dV/dtmax). Peak aortic blood acceleration (GAo) was
      simultaneously measured from the suprasternal notch using a pulsed Doppler
      velocity meter. In the branchial and the common carotid arteries, Gmax was of a
      similar magnitude (551 +/- 30 and 555 +/- 44 cm/s2, respectively) despite major
      differences in the respective D, Vm, Q and R values. In neither artery was there
      a relationship between Gmax and either resting Q or R. At the brachial artery
      level, Gmax was positively related to GAo (r = 0.79, P = 0.0008). At the common
      carotid artery level, there was a weak, although non significant relationship
      between Gmax and GAo (P = 0.08). Our results indicate that the local acceleration
      of peripheral blood flow in the brachial artery is related rather to upstream
      central impulse than to downstream hemodynamics, and suggest some regional
      differences in the hemodynamic determinants of the local acceleration of
      peripheral blood flow.

PMID- 8871140
TI  - Effect of angiotensin converting enzyme inhibitors on quality of life in
      hypertensive patients. Pharmacodynamic basis.
AB  - The aim of this review is to comment the results described in the literature
      concerning the possible pharmacodynamic mechanisms involved in the improvement of
      quality of life of angiotensin converting enzyme inhibitors that is just a
      working hypothesis. These drugs, widely used in the treatment of hypertension,
      prevent the formation of angiotensin II and the generation of free radicals, as
      well as the hydrolysis of bradykinin, enkephalins and endorphins. Different
      mechanisms have been implicated on quality of life: 1) increase of bradykinin
      levels in the central nervous system that would trigger the release of nitric
      oxide (NO), noradrenaline, acetylcholine, excitatory amino acids and vasopressin
      which are involved in memory and cognition; 2) increase of brain blood supply by
      enhanced NO synthesis; 3) interference with cholinergic mechanisms in the central
      nervous system by angiotensin II inhibition of acetylcholine release; 4) decrease
      of endorphin metabolism; and 5) interaction with hypothalamic-pituitary-adrenal
      axis that releases ACTH and vasopressin.

PMID- 8871141
TI  - Tropisetron inhibits the antinociceptive effect of intrathecally administered
      paracetamol and serotonin.

PMID- 8871142
TI  - Diagnostic vitrectomy and chronic uveitis.
AB  - BACKGROUND: From the introduction of vitrectomy, infectious endophthalmitis was
      one of the indications for this surgical technique. Vitrectomy was later found to
      be a valuable method in both diagnostic and therapeutic evaluation of chronic
      uveitis. METHODS: Twenty-eight eyes of 25 patients were operated on with purely
      diagnostic intent. These were patients not responding, or no longer responding,
      to their cortisone treatment and for whom no etiology had been found previously.
      RESULTS: Vitrectomy itself yielded the diagnosis in nine eyes of eight patients.
      Three had unexpected infectious pathology (one bacterial, one mycotic, one
      viral), while five had tumoral pathology four with non-Hodgkin lymphoma and one
      with a metastasis of a malignant melanoma of the skin. In four other patients,
      typical fundus lesions were seen during the surgery, providing a clue to the
      etiology: three cases of retinal necrosis and one case of a pseudotumoral mass
      suggestive of Toxocara canis. Serologic tests confirmed three cases of herpes
      simplex infection and one of Toxocara canis. Apart from the fact that a diagnosis
      could be made in half of the patients, the diagnostic vitrectomy also had a
      favorable effect upon vision in half the cases. CONCLUSION: In cases of chronic
      uveitis where no etiology has been found, vitrectomy is able to provide a
      diagnosis in about one-third of eyes directly. During surgery a typical
      appearance of the fundus may reveal a supplementary diagnosis, resulting in an
      overall diagnosis in about half of the cases. Moreover, half of the patients will
      have improved vision after surgery.

PMID- 8871143
TI  - Haemorheology in patients with branch retinal vein occlusion with and without
      risk factors.
AB  - PURPOSE: The study was carried out to ascertain the role of blood viscosity in
      patients with branch retinal vein occlusion (BRVO) with and without risk factors.
      METHODS: In 292 patients with acute BRVO (mean age 65 +/- 10 years) and 292
      controls matched for gender, age, and cardiovascular risk factors, haematocrit,
      plasma viscosity, erythrocyte aggregation and erythrocyte rigidity were measured.
      A subgroup analysis in patients with and without risk factors was performed.
      RESULTS: Haematocrit and plasma viscosity values were significantly higher in
      BRVO patients than in controls, but erythrocyte rigidity and erythrocyte
      aggregation did not differ. Subgroup analysis revealed no differences in
      haematocrit and plasma viscosity values between patients with and those without
      cardiovascular risk factors. CONCLUSIONS: This study shows increased plasma
      viscosity and haematocrit values in patients with BRVO which are not associated
      with the presence of other cardiovascular risk factors. Thus, changes in blood
      fluidity appear to be important factors in the pathogenesis of BRVO.

PMID- 8871144
TI  - Identification of individual microaneurysms: a comparison between fluorescein
      angiograms and red-free and colour photographs.
AB  - PURPOSE: To evaluate how often a microaneurysm (MA) seen in a fluorescein
      angiogram (FAG) is visualized in colour or red-free photographs, and conversely
      how often a red dot seen in a colour photograph or a red-free photograph is found
      in an FAG as an MA. METHOD: Sixty-degree FAGs, colour photographs and red free
      fundus photographs of 24 patients with mild background retinopathy were analysed
      using a computer-assisted fundus lesion localization system. Only lesions
      identified similarly in two separate sessions were processed further. The
      presence of lesions identified by their position was compared in FAGs and colour
      and red-free photographs. RESULTS: In the whole material 394 MAs were detected in
      FAGs, 95 in red-free and 62 in colour photographs. Of the MAs in FAGs 26 (6.6%)
      were seen as a red dot in a colour photograph and 52 (13%) were found in red-free
      photographs. Of the 95 MAs found in red-free images 52 (55%) were detected in
      FAGs. Of the 62 MAs in colour photographs, 26 (42%) were seen as a MA in a FAG. A
      significant correlation existed between MA counts in FAGs and red dot counts in
      colour or red-free photographs of individual patients. CONCLUSIONS: Although MAs
      in FAG and red spots in colour or red-free photographs all reflect the degree of
      retinopathy, about half of the red dots in photographs do not represent open MAs
      in FAGs.

PMID- 8871145
TI  - Serum retinoids in retinitis pigmentosa patients treated with vitamin A.
AB  - BACKGROUND: Patients with retinitis pigmentosa have been suggested to benefit
      from treatment with moderate doses of retinyl palmitate. Retinyl palmitate is not
      an active retinoid in itself but is metabolised to active components in the body.
      To find out which metabolites of retinyl palmitate were formed and at which
      concentrations, we measured the concentrations of retinol, retinyl palmitate,
      retinoic acids and tocopherol in serum of patients treated with oral retinyl
      palmitate for retinitis pigmentosa. METHODS: Nine male patients and one female
      diagnosed as having retinitis pigmentosa after a complete ophthalmological
      examination including a full-field electroretinogram were given vitamin A at
      their own request as one daily morning dose of 16600 IU vitamin A. Blood samples
      were obtained before and after > 2 weeks of treatment. The concentrations of
      retinoids and tocopherol were measured with established methods. RESULTS: The
      patients were not deficient in vitamin A or vitamin E as judged from the serum
      vitamin concentrations. Treatment with retinyl palmitate significantly increased
      the serum concentration of retinyl palmitate and of 13-cis-retinoic acid but not
      of retinol, tocopherol or all-trans-retinoic acid. CONCLUSIONS: Neither retinyl
      palmitate nor 13-cis-retinoic acid, are known to be biologically active. However,
      13-cis-retinoic acid can isomerise to the active vitamin A derivative, all-trans
      retinoic acid. It is suggested that patients may be treated with a small dose of
      13-cis-retinoic acid instead, to avoid the relatively long metabolic detour from
      retinyl palmitate.

PMID- 8871147
TI  - Retinal damage and laser-induced breakdown produced by ultrashort-pulse lasers.
AB  - BACKGROUND: In vivo retinal injury studies using ultra-short-pulse lasers at
      visible wavelengths for both rabbit and primate eyes have shown that the degree
      of injury to the retina is not proportional to the pulse energy, especially at
      suprathreshold levels. In this paper we present results of calculations and
      measurements for laser-induced breakdown (LIB), bubble generation, and self
      focusing within the eye. METHODS: We recorded on video and measured the first in
      vivo LIB and bubble generation thresholds within the vitreous in rabbit and
      primate eyes, using external optics and femtosecond pulses. These thresholds were
      then compared with calculations from our LIB model, and calculations were made
      for self-focusing effects within the vitreous for the high peak power pulses.
      RESULTS: Results of our nonlinear modeling and calculations for self-focusing and
      LIB within the eye were compared with experimental results. The LIB ED50 bubble
      threshold for the monkey eye was measured and found to be 0.56 microJ at 120 fs,
      compared with the minimum visible lesion (MVL) threshold of 0.43 microJ at 90 fs.
      Self-focusing effects were found to be possible for pulsewidths below 1 ps and
      are probably a contributing factor in femtosecond-pulse LIB in the eye.
      CONCLUSIONS: Based on our measurements for the MVL thresholds and LIB bubble
      generation thresholds in the monkey eye, we conclude that in the femtosecond
      pulsewidth regime for visible laser pulses, LIB and self-focusing are
      contributing factors in the lesion thresholds measured. Our results may also
      explain why it is so difficult to produce hemorrhagic lesions in either the
      rabbit or primate eye with visible 100-fs laser pulses even at 100 microJ of
      energy.

PMID- 8871146
TI  - Adenocarcinoma of the retinal pigment epithelium: a diagnostic and therapeutic
      challenge.
AB  - BACKGROUND: Adenocarcinoma of the retinal pigment epithelium (RPE) is an uncommon
      intraocular tumor which has been rarely if ever diagnosed prior to enucleation.
      Our review of the literature suggests that when a melanotic and tuberous-shaped
      tumor presents in a woman with signs of uveitis one should consider the diagnosis
      of adenocarcinoma of the RPE. METHODS: We report a case in which a 4.9-mm-tall,
      mushroom-shaped, moderately reflective melanotic tumor found to be present in a
      50-year-old woman. Other findings included a 12 x 10-mm dense transillumination
      shadow and 270 deg of posterior iris synechiae. With a presumptive diagnosis of
      uveal melanoma the patient was treated with palladium-103 plaque radiotherapy.
      Within 6 months she underwent enucleation due to uncontrollable ocular pain and
      progressive tumor growth. Histopathologic evaluation revealed an adenocarcinoma
      of the (RPE). RESULTS: Two months after radiotherapy the eye developed acute
      angle-closure glaucoma, secondary retinal detachment, and a painful scleritis (a
      result similar to that of Greer, who treated an intraocular adenoma with
      radiation). Our diagnosis of adenocarcinoma of the RPE was made after
      enucleation. CONCLUSION: Adenocarcinomas of the RPE are rarely if ever diagnosed
      on clinical evaluation, should be suspected in women with a melanotic intraocular
      tumor and uveitis, and may respond poorly to ophthalmic plaque radiotherapy. All
      reported cases presenting without extrascleral extension have not metastasized.

PMID- 8871148
TI  - Scleral buckling surgery in stage 4 retinopathy of prematurity.
AB  - BACKGROUND: Technical advances in neonatal intensive care have significantly
      increased the number of very low birth-weight babies that survive the perinatal
      period. Some of these infants develop severe retinopathy of prematurity that may
      lead to retinal detachment. METHODS: Between November 1988 and January 1994, 28
      eyes from 15 preterm babies underwent scleral buckling for stage 4 retinopathy of
      prematurity at a mean age of 4.2 months. Cryotherapy was performed preoperatively
      on 12 eyes and intraoperatively in the remaining 16 eyes. The mean follow-up
      period was 35 months. RESULTS: Scleral buckling produced retinal reattachment in
      13 eyes (46.4%). Severe myopia (-5 D to -15 D) was found in all 13 of these eyes,
      12 also presented convergent strabismus. Mean visual acuity, measured in 6 eyes
      from children over the age of 3 years was 20/40. In 7/28 eyes of the younger
      children of this group we found a fix and follow the light capability. No light
      perception was detected in 11/28 eyes; in the remaining 4/28 eyes there was only
      light perception. Scleral buckling failed to prevent the progression to stage 5
      in 15 eyes (53.6%). Additional surgery was excluded for 9 of these eyes based on
      ultrasonography findings; the other 6 eyes underwent vitrectomy, which led to
      macular reattachment in 4 cases. CONCLUSIONS: Clinical experience shows that
      scleral buckling is not always capable of preventing progression of the disease
      to stage 5. Furthermore, even when the anatomic results of this procedure are
      good, the functional outcome is often complicated by severe visual impairment.

PMID- 8871149
TI  - Surgical removal of idiopathic, myopic and age-related subfoveal
      neovascularization.
AB  - BACKGROUND: We investigated the functional outcomes of macular surgery for
      idiopathic, myopic and age-related subfoveal neovascular membranes and looked for
      preoperative features associated with better final visual acuity (VA). METHODS:
      We retrospectively studied 61 patients who had undergone macular surgery in our
      department between October 1992 and September 1994. Follow-up ranged from 5 to 27
      months. Of 61 eyes with subfoveal neovascularizations, 6 were idiopathic, 21 had
      high myopia (-13 D median) and 34 displayed age-related macular degeneration
      (AMD). Median preoperative VA was 5/200 in AMD, 20/300 in myopia and 20/200 in
      idiopathic cases. RESULTS: Four of the six eyes with idiopathic subfoveal
      neovascularization had VA 20/60 or better after a median follow-up of 18 months.
      Of the 21 eyes with high myopia, 10 (48%) improved and 13 (62%) were 20/200 or
      greater after a median follow-up of 12 months. Among the 34 eyes with AMD, VA
      improved in 7 (21%), but only 6 (18%) were 20/200 or better after a median follow
      up of 7 months. Overall, complications included five retinal detachments, ten
      cataracts and an increase in size of the retinal pigment epithelium defect over
      the neovascular membrane of 2.3 +/- 0.8 times (mean +/- SD) in idiopathic eyes.
      5.9 +/- 3.6 times in myopia and 19.5 +/- 12.2 times in AMD. Recurrence rates for
      idiopathic, myopic and age-related neovascular membranes were 33%, 19% and 18%
      respectively. Etiology (P = 0.035), initial VA in myopic eyes (P = 0.026) and
      initial size of the neovascular membranes in AMD (P = 0.025) were preoperative
      factors with a significant effect on final visual outcome. CONCLUSIONS: Surgical
      excision of subfoveal neovascular membranes yields different functional results
      depending on the underlying disease. Severe alteration of the retinal pigment
      epithelium-Bruch's membrane complex may be responsible for the poor visual
      outcomes in AMD.

PMID- 8871150
TI  - Prognostic factors associated with the visual outcome after vitrectomy for
      endophthalmitis.
AB  - BACKGROUND: Functional results following vitrectomy with intraocular and systemic
      antibiotic treatment for endophthalmitis are influenced by numerous factors.
      METHODS: A retrospective study of 65 cases of endophthalmitis treated between
      October 1988 and May 1994 at the Department of Ophthalmology, University of
      Cologne, Germany was conducted. All eyes underwent pars plana vitrectomy and
      intraocular and systemic antibiotic treatment. RESULTS: Vision of 20/400 or
      better could be obtained in 66% of eyes following extracapsular cataract
      extraction and intraocular lens implantation (ECCE + IOL), in 62% after severe
      eye injury, in 36% of eyes after intraocular surgery for other reasons than
      cataract extraction with lens implantation and in 33% of patients with endogenous
      endophthalmitis. Vision of 20/50 or better could be achieved in 41% of eyes
      following ECCE + IOL and additional systemic steroid treatment. In 22% of cases
      primary silicone endotamponade was performed; 57% of these eyes obtained visual
      acuity of 20/400 or better. Fifteen patients (23%) suffered diabetes mellitus;
      20/400 vision or better could be achieved in 73% of these eyes. Visual acuity of
      hand movements or better before vitrectomy was associated with 20/400 vision or
      better in 69% of cases, whereas ambulatory vision could be attained in only 33%
      of patients with visual acuity of worse than hand movements at the initial
      presentation. Visual acuity of less than 20/400 was found in all eyes with
      haemolytic streptococcal infections. CONCLUSION: Prompt treatment of
      endophthalmitis is crucial. Additional treatment using systemic steroids and, if
      necessary, silicone oil can improve the functional outcome in some cases.

PMID- 8871151
TI  - Penetration of gentamicin and ofloxacin in human vitreous after systemic
      administration.
AB  - BACKGROUND: Data on the penetration of antibiotics into the aqueous humor in man
      and animals, as well as on the intravitreal penetration in animals, are numerous.
      Data on their intravitreal penetration in humans, however, are sparce. The
      intravitreal penetration of gentamicin was studied in different ocular
      pathologies to see whether these alter the vitreal pharmacodynamics. The
      intravitreal penetration of ofloxacin, a fluoroquinolone, was determined to see
      whether levels sufficient to treat infectious endophthalmitis could be reached.
      METHODS: The intravitreal penetration of gentamicin and ofloxacin was studied in
      patients undergoing pars plana vitrectomy for various ocular pathologies. Those
      with recent hemorrhages and those already receiving general antibiotic treatment
      were excluded. RESULTS: Gentamicin was found to penetrate the vitreous very
      poorly. No difference could be found between the various pathologies: trauma,
      diabetes, proliferative vitreoretinopathy, longstanding vitreous hemorrhage and
      macular pucker gave the same poor penetration. The ofloxacin levels were higher
      but did not reach the MIC90 levels of most organisms involved in bacterial
      endophthalmitis. CONCLUSION: The hemato-ocular barrier is more difficult to cross
      than originally thought. Different ocular pathologies do not alter the ocular
      barrier substantially. Ofloxacin alone does not seem to be sufficient for the
      treatment of established bacterial endophthalmitis.

PMID- 8871152
TI  - Intraocular oxygen tension in eyes with proliferative diabetic retinopathy with
      and without vitreous.
AB  - BACKGROUND: Intraocular oxygen tension was measured in the eyes of patients with
      proliferative diabetic retinopathy with or without vitreous in order to determine
      local differences in tissue oxygenation in the vitreous cavity before and after
      vitrectomy. METHODS: We measured oxygen tension, using polarographic oxygen
      electrodes, at various intraocular locations in 30 eyes of 29 patients with
      diabetic traction retinal detachment who were candidates for vitrectomy (pre
      vitrectomy group) and 13 eyes of 13 diabetic patients who had previously
      undergone vitrectomy (post-vitrectomy group). RESULTS: In the pre-vitrectomy
      group, oxygen tensions proximal to the neovascularization of the disc and the
      neovascularization elsewhere were significantly higher than the values obtained
      at other locations in the vitreous cavity. In the post-vitrectomy group, however,
      the oxygen tensions at those locations were significantly lower than those in the
      pre-vitrectomy group. There were no significant differences between the values
      obtained at any of the measurement locations in the post-vitrectomy eyes.
      CONCLUSION: Neovascular tissues in the eyes of diabetic patients demonstrated
      higher oxygen tensions than non-neovascular tissues. This finding suggests that
      neovascular issue may compensate for intraocular hypoxia by releasing oxygen from
      the front. Successful diabetic vitrectomy reduces the activity of the neovascular
      tissue and equalizes levels of oxygenation in the tissue of the vitreous cavity.

PMID- 8871153
TI  - Malignant tumor of the retinal pigment epithelium with extraocular extension in a
      phthisical eye.
AB  - BACKGROUND: Malignant tumors of the retinal pigment epithelium (RPE) are
      exceedingly rare. We describe the histopathologic and immunohistochemical
      features of a RPE neoplasm that was found accidentally in a blind and painful
      phthisical eye. METHODS: The enucleated eye was investigated by light microscopy,
      and tumor tissue was also studied by electron microscopy. Immunohistochemistry
      was performed using antibodies against HMB-45, S-100 protein, NSE, cytokeratins,
      vimentin, desmin, GFAP, the HNK-1 carbohydrate epitope and alpha-smooth muscle
      actin. RESULTS: The tumor was located mainly in the vitreous cavity with
      practically complete destruction of the retina, but foci of choroidal
      infiltration and extraocular extension along vascular channels were identified.
      The mitotic rate was high, and large areas of necrosis were present. No features
      of differentiation were seen, apart from occasional desmosome-like junctions and
      deposition of basal lamina at the ultrastructural level. Adjacent to the tumor,
      reactive hyperplasia and metaplasia of RPE cells was prominent. By
      immunohistochemistry, tumor cells revealed intense immunoreactivity with anti
      vimentin and weak staining with anti-S-100 protein. The hyperplastic RPE cells
      also reacted for cytokeratins 8, 18 and 19 and for alpha-smooth muscle actin. At
      more than 1 year post enucleation the patient is well and shows no signs of
      recurrence or metastatic disease. CONCLUSION: We present the features of a
      malignant tumor of the RPE with unequivocal extraocular extension. These findings
      raise the possibility that RPE hyperplasia may transform into a malignant tumor.

PMID- 8871154
TI  - Retinal pigment epithelial cell proliferation: potentiation by monocytes and
      serum.
AB  - BACKGROUND: The development of proliferative vitreoretinopathy (PVR) results
      often from a breakdown of the blood-retina barrier and the intraocular
      accumulation of serum proteins and leukocytes, particularly monocytes, that then
      come into contact with retinal pigment epithelial (RPE) cells. To examine the
      effect of these two factors on RPE proliferation, which is characteristic of PVR,
      we used a coculture system of blood monocytes and human RPE cells. METHODS: RPE
      cells were incubated with a variable number of monocytes at different serum
      concentrations and assayed for proliferation by [3H]-thymidine incorporation and
      cell counting. To assess cell-cell communication. RPE cells were labeled with 2',
      7' -bis(carboxyethyl)-5(and 6) carboxyfluorescein acetoxy-methyl ester, and the
      dye transfer to monocytes was analyzed using an UV microscope. RESULTS: Monocytes
      (P < 0.0004) and serum (P < 0.0001), each on its own, significantly stimulated
      RPE cell growth, and these two variables were interrelated (P < 0.0001), showing
      a potentiating synergism. In serum-free medium, monocytes increased proliferation
      to just above control levels, whereas the same number of monocytes in 5% serum
      increased the [3H]-thymidine incorporation 3.8 times. This effect was greatly
      reduced by prevention of direct cell contact by means of placement of a well
      insert, which also lessened the monocyte-induced proliferation in both serum-free
      and serum-containing medium. Furthermore, the transfer of the intracellular dye
      from RPE cells to cocultured monocytes indicates that RPE cells transferred parts
      of their cytoplasm to monocytes. CONCLUSION: These observations underline the
      importance of protein leakage through a damaged blood-ocular barrier and of
      direct contact of monocytes/macrophages with RPE cells, as well as their
      reciprocal potentiating effect on RPE cell proliferation. Thus, early
      stabilization of the blood-ocular barrier, which would preclude or reduce protein
      leakage and invasion of inflammatory cells into the eye, could be a target for
      pharmacologic prevention of PVR.

PMID- 8871155
TI  - T-cell subsets and T-cell receptor V beta utilization by Igh-1-congenic mice in
      herpetic retinal necrosis.
AB  - BACKGROUND: After unilateral anterior chamber (AC) inoculation with herpes
      simplex virus type 1 (HSV-1), C.B-17 and BALB/c congenic mice, which differ only
      in a limited region around the lgh-1 locus on chromosome 12, show a striking
      difference in susceptibility to development of encephalitis and contralateral
      necrotizing chorioretinitis. METHODS: After AC inoculation with HSV-1 (KOS), C.B
      17 and BALB/c mice were followed up for the clinical signs of encephalitis and
      chorioretinitis. At different time points following inoculation, lymphocytes
      isolated from the spleen were triple-stained with antibodies directed against CD4
      or CD8, IL-2R, and various V beta T-cell receptor (TCR) subsets, and were
      analyzed by flow cytometry. RESULTS: These lgh-1-disparate congenic mice showed
      differences in the time course of splenic V beta T-cell receptor (TCR) usage in
      both CD4+, IL-2R+ and CD8+, IL-2R+ T cells. By day 1 post infection (p.i.), C.B
      17 mice showed an increase of V beta 8 and V beta 9 TCR by both CD4+, IL-2R+ and
      CD8+, IL-2R+ splenic T cells. Susceptible BALB/c mice delayed the increase of
      splenic V beta 8 and V beta 9 TCR by CD4+, IL-2R+ T cells, which was noted by day
      4 p.i. Furthermore, in BALB/c mice the usage of V beta 9 by CD8+ cells was
      increased by day 6 p.i. CONCLUSIONS: Our findings indicate that early
      preferential splenic usage of a restricted repertoire of TCR occurs after ocular
      inoculation with HSV-1 in resistant C.B-17 mice. Such preferential TCR usage by
      activated T cells may prevent viral replication in the brain and contralateral
      eye and may be linked to protection from development of encephalitis and
      destructive herpesmediated ocular inflammation.

PMID- 8871156
TI  - Density-dependent growth regulation of pig retinal pigment epithelial cells in
      vitro.
AB  - BACKGROUND: Transplantation of the retinal pigment epithelium (RPE) involves
      delivering donor RPE onto a bare area of host Bruch's membrane that is surrounded
      by a confluent monolayer of RPE. We investigated the effects of different plating
      densities and the presence of an adjacent confluent monolayer on the growth
      characteristics and final morphology of pig RPE in vitro. METHODS: In single-well
      experiments, porcine RPE were plated in 24-well plates at densities varying from
      1 to 75 cells/mm2. Triplicate plates were counted on the 3rd and 10th days after
      plating and at confluence. A multiwell chamber was built to allow cells plated at
      different densities to be bathed with conditioned media from adjoining wells.
      RESULTS: In single-well experiments, plating at low densities increased the time
      to reach confluence and resulted in fewer, larger and more fusiform RPE at
      confluence. In multiwell experiments, the growth rate of cells plated at low
      density decreased as the amount of high-density medium increased in communicating
      wells and led to smaller, rounder cells at confluence. The presence of low
      density RPE in adjoining wells increased the growth rate of RPE plated at high
      density and produced fewer, larger and more fusiform cells at confluence. Newly
      plated RPE grew more slowly when confluent monolayers of RPE were present in
      adjoining wells. CONCLUSIONS: Plating density is a critical factor in determining
      the growth rate and the final morphology of RPE in tissue culture. The presence
      of a neighboring confluent monolayer of RPE inhibits the growth rate of newly
      plated RPE in vitro.

PMID- 8871157
TI  - Nerve growth factor delays retinal degeneration in C3H mice.
AB  - BACKGROUND: The aim of the present study was to investigate the biological role
      of nerve growth factor (NGF) on retinal degeneration in the C3H mouse strain.
      This strain is characterized by a single gene mutation (rd) which leads to
      photoreceptor degeneration resembling human retinitis pigmentosa. METHODS: Neural
      retinas from 1- to 25 day-old C3H mice were dissected from outer ocular tissues,
      dissociated in cell suspension, stained with a vital dye and counted in a
      hemocytometer. For in vivo study, NGF was injected into the intraocular or retro
      ocular area, and at the end of the treatment the mice were killed. The eyes were
      enucleated, fixed and cut by cryostat into 14-microns serial sections. The serial
      sections were stained with hematoxylin-eosin and the outer nuclear layer (ONL)
      was measured using a computerized image analysis system. RESULTS: An intraocular
      injection of NGF, or repeated retro-ocular injections, induced a significant
      increase in ONL thickness compared to controls. CONCLUSION: Our data show that
      NGF inhibits retinal degeneration in C3H mice. The mechanism(s) underlying the
      protective action of NGF against retinal cell death remains to be established.

PMID- 8871158
TI  - Electron microscopic study of retinas of macular mice.
AB  - BACKGROUND: Menkes' disease may be due to a lack or deficiency of copper in
      various organs. The macular mouse is known as a model for Menkes' disease. We
      examined melanin granules in the retinal pigment epithelium and the activity of
      cytochrome oxidase, a copper-containing enzyme, in the retinas of macular mice by
      electron microscopy. METHODS: In the retinas of hemizygote macular mice we
      demonstrated cytochemically (oxidative polymerization of diaminobenzidine to an
      osmophilic reaction product) the activity of cytochrome oxidase. The distribution
      of melanin granules in the retinal pigment epithelium related to the activity of
      another copper-containing enzyme, tyrosinase was also studied. Stereological
      methods were applied to obtain quantitative data. RESULTS: In the retinal
      photoreceptor inner segments of the macular mouse, the mitochondria were more
      numerous than in normal litermates and they appeared swollen. There were fewer
      melanin granules in the retinal pigment epithelium of macular mice than in that
      of normal littermates. The cytochrome oxidase activity was significantly lower in
      the macular mice than in the controls. CONCLUSION: Macular mice have lower
      activity of cytochrome oxidase and fewer melanin granules than do normal mice.
      Both changes may be related to copper deficiency. These results correspond to the
      retinal changes seen in patients with Menkes' disease.

PMID- 8871159
TI  - Does the human cornea contain silicon?
AB  - BACKGROUND: Our study investigated the presence, type and quantity of silicon in
      the human cornea. We report the results of silicon measurements in the corneas of
      silicotic individuals, bricklayers and apparently normal human individuals and
      offer a hypothesis for the mechanism of silicon deposition in the human cornea.
      METHODS: We examined corneas from 13 decreased subjects who suffered from
      silicosis, 2 bricklayers and 6 apparently healthy subjects. Cornea samples were
      examined by energy-dispersive x-ray analysis (EDXA) under calibrated conditions
      in a scanning electron microscope (SEM). The EDXA detector was a silicon-free
      germanium crystal. Five distinct layers (epithelium, Bowman's membrane, central
      stroma. Descemet's membrane and endothelium) were analyzed in each cornea. The
      method allows simultaneous semiquantitative analysis of, among other elements,
      silicon, calcium and oxygen. We measured amorphous silicon and visible particles
      of silicon. RESULTS: We found amorphous silicon in low concentrations in 38% of
      the silicotic corneas and in very low concentrations in 29% of the healthy
      corneas. Bricklayers showed high concentrations of amorphous silicon. These
      accumulations of silicon were predominantly located in Descemet's membrane.
      Silicotic corneas showed significantly more silicon-containing particles than
      corneas of healthy controls (chi 2-test, P < 0.01). CONCLUSION: Normal corneas
      contain very low amounts of silicon. Longterm exposure to inhalative silicon
      dusts results in only very slightly increased levels of amorphous silicon in the
      cornea. However, silicon-containing particles accumulate in the cornea of
      silicotic individuals. Bricklayers incorporate more amorphous silicon into the
      cornea.

PMID- 8871160
TI  - Vimentin and cytokeratin pattern in granular corneal dystrophy.
AB  - BACKGROUND: Corneal granular dystrophy is usually classified as a hereditary
      stromal disease of the cornea. Some investigations, however, have indicated an
      epithelial rather than a stromal origin of the granular deposits. In early stages
      and in recurrences of granular dystrophy after keratoplasty, the deposits are
      most often found in the upper microlayers of the cornea and even
      intraepithelially. METHODS: In this study we tried to identify
      immunohistochemical epithelial markers in the corneal granular deposits. RESULTS:
      A positive reaction with anti-cytokeratin 18 and polyclonal anti-vimentin were
      found both in the corneal epithelium and in the granular deposits. CONCLUSION:
      The immunohistochemical findings support the hypothesis of an epithelial origin
      of the corneal deposits in granular dystrophy.

PMID- 8871161
TI  - Systemic ciclosporin A in high-risk keratoplasties.
AB  - BACKGROUND: It was the purpose of this study to compile the results of all high
      risk keratoplasties (kp) performed in our hospital under systemic ciclosporin A
      (Ci A) cover from 1987 through 1994. METHODS: One hundred and thirty-one
      keratoplasties were performed. Ci A was administered for an average period of 9.4
      months. We aimed at trough levels of 100-150 ng/ml (monoclonal RIA/TDx). The 29
      kp in group A were second or third repeat kp and/or the recipient cornea had
      severe deep vascularization in all quadrants and/or a transplant position at the
      limbus was inevitable (expected risk: only immune reactions). The 40 kp in group
      B were threatened by severe ocular surface disorders (without severe limbal stem
      cell insufficiency) and by immune reactions (atopic keratopathy, keratoconus with
      severe endogenous eczema or chronic blepharokeratoconjunctivitis). In the 45 kp
      of group C resurfacing problems from severe limbal stem cell insufficiency and
      immune reactions were anticipated (severe burns, pseudopemphigoid or Lyell
      syndrome). Group D comprised 17 kp with various diagnoses (e.g. kp in newborns,
      rheumatic and Acanthamoeba keratitis). RESULTS: In group A 91% of the grafts were
      clear 2 years postoperatively, in group B 76%, in group C 38% and in group D 18%.
      In 32 of 41 failed grafts (78%), resurfacing problems were the only reason for or
      participated in final graft failure. Immune reactions and other causes of graft
      failure were of minor importance. CONCLUSIONS: (1) Systemic Ci A cover can
      efficiently suppress immune reactions. (2) With the suppression of immune
      reactions, resurfacing disorders become the most important single cause for
      functional graft failure. (3) For eyes with a considerable loss of limbal stem
      cells, limbal stem cell transplantation should be combined with systemic Ci A
      cover in order to improve the long-term prognosis for penetrating keratoplasty.

PMID- 8871162
TI  - Central corneolimbal transplantation under systemic ciclosporin A cover for
      severe limbal stem cell insufficiency.
AB  - BACKGROUND: Severe stem cell deficiencies uniformly lead to superficial
      conjunctivalization of corneal grafts with subsequent functional failure. We
      sought better long-term results by transplanting central corneolimbal grafts and
      simultaneously protecting the graft and its stem cells from immunological
      destruction by means of systemic administration of ciclosporin A. PATIENTS AND
      METHODS: In an ongoing pilot study, up to April 1995 20 eyes with stem cell
      dysfunctions of various etiology (e.g. chemical burn, ocular pseudopemphigoid,
      congenital aniridia) received eccentrically trephined fresh corneal grafts of 7.7
      10.0 mm diameter. About one third of the circumference of the grafts contained
      limbal area. The mean age of the patients was 46.2 years (range 9-84 years). All
      patients received systemic ciclosporin A for at least 12 months. At present, the
      mean follow-up period is 9.6 months (mean 1-20.6 months). RESULTS: Fourteen of 20
      grafts (70%) have remained clear so far. Reasons for six graft failures were
      surface disorders in four eyes, immune reactions in one eye and surface disorders
      in combination with immune reactions in another eye. Ten of 20 grafts (50%)
      experienced severe surface disorders. In six eyes surface disorders were
      coincident with endothelial immune reactions, in four eyes they were not. In four
      of 20 grafts (20%) conjunctivalization was observed in front of the transplanted
      limbal area; in seven of 20 grafts (35%) conjunctivalization occurred only
      distant from the transplanted limbal stem cells. CONCLUSIONS: Our method of
      central corneolimbal transplantation with simultaneous protection of the
      transplanted stem cell population from immunological destruction by means of
      systemic ciclosporin A has been successful for 14 eyes with severe stem cell
      deficiencies up to 20.6 months postoperatively. This new treatment principle
      promises - for the first time - long-term rehabilitation for a majority of eyes
      with severe limbal stem cell deficiencies.

PMID- 8871163
TI  - Clinical characteristics of acyclovir-resistant herpetic keratitis and
      experimental studies of isolates.
AB  - BACKGROUND: We treated two patients with dendritic keratitis that did not respond
      to acyclovir (ACV) ointment therapy. Their systemic immune status was normal:
      however, one patient had a long history of atopic disease and the other had
      previously undergone topical corticosteroid treatment. HSV-1 was isolated from
      the patients and inoculated into animals to investigate its viral pathogenicity
      and latent infection. METHODS: HSV-1 isolates from the patients were tested for
      drug sensitivity to acyclovir, ganciclovir, idoxuridine, trifluridine, foscarnet
      and interferon-beta in vitro. In in vivo studies, bilateral corneas of two New
      Zealand white rabbits and 10 BALB/c mice in each of four groups were infected by
      the respective viral isolates. The extent of corneal epithelial and/or stromal
      lesions produced by the viruses was evaluated. The trigeminal ganglial tissues of
      the mice were examined for viral latent infection by co-culture with Vero cells.
      RESULTS: Herpetic keratitis in both patients was characterized by prolonged
      clinical course, succeeded by various types of corneal lesions and ocular
      complications. In in vitro studies, the two HSV-1 isolates demonstrated cross
      resistance to ACV, ganciclovir and/or idoxuridine. Both strains demonstrated
      weakly virulent corneal epithelial and/or stromal lesions in rabbits and mice.
      One isolate displayed delayed advent but prolonged course of epithelial lesions
      in rabbits. The latent infection incidences of the isolates in mice trigeminal
      ganglia were 6.25% (1/16) and 0% (0/18) respectively. CONCLUSION: Topical immune
      depression may induce ACV-resistant HSV-1 infection in the cornea, with a
      prolonged course in association with ocular complications. The prolonged
      infectious course of the viral isolates in the animal study partially supported
      the clinical demonstrations in the patient. The existence of latent infection by
      one ACV-resistant HSV-1 in its animals may indicate the possibility of its
      recurrence. Trifluridine may be an alternative choice for treating corneal
      epithelial lesions caused by ACV-resistant HSV-1.

PMID- 8871165
TI  - Dapiprazole for patients with night haloes after excimer keratectomy.
AB  - BACKGROUND: Haloes causing difficulties during the night driving are one of the
      common complications of photorefractive keratectomy (PRK). The presumed reason
      for this phenomenon is the different refraction of light through the treated and
      untreated areas of the cornea. Its magnitude is proportional to the ratio between
      the treated area and pupil size. At nighttime, when the pupil dilates, rays from
      treated and untreated areas of the cornea reach the retina at different foci and
      produce haloes. We investigated whether dapiprazole, a miotic alpha-blocker drug,
      would be helpful in reducing night haloes in patients after PRK. METHODS: Twenty
      four patients who complained of night haloes after PRK participated in our study.
      All were given dapiprazole 0.5% before night driving. Change in pupil size was
      recorded, and all patients completed a questionnaire on changes in the severity
      of haloes after instillation of dapiprazole. RESULTS: Improvement was described
      as very significant in five patients, moderate in ten and slight in seven. There
      was no improvement in two patients. The only side effect was slight irritation,
      which resolved within 1 h. CONCLUSION: Our results demonstrate that dapiprazole
      improves the subjective discomfort caused by night haloes in post-PRK patients.

PMID- 8871166
TI  - Thermal effects in excimer laser trephination of the cornea.
AB  - BACKGROUND: Excimer laser trephination, as an alternative to mechanical
      trephination of the cornea in penetrating keratoplasty, is expected to reduce
      long-term postkeratoplasty astigmatism. Trephination with high energy densities
      may induce thermal epithelial alterations when metal aperture masks are used.
      METHODS: Ninety porcine eyes fixed in an artificial anterior chamber (20 mmHg)
      were trephined with a 193-nm excimer laser in order to study the effect of the
      temperature on the cornea and the aperture mask during and after termination of
      the laser exposure. Energy levels tested were in the range used in patients. A
      pyroelectric infrared sensor connected to a PC via an analog-digital converter
      was used. With a high-speed sampling routine written in C+2 it was possible to
      monitor on line the temperature in a focus 0.8 mm in diameter. RESULTS: In donor
      trephination the maximum temperature increase of the metal mask was 11 K (donor
      tissue 6.1 K, repetition rate 30/s). During recipient trephination the maximum
      temperature increase of the mask was 9.4 K (7.5 K on the cornea). An increase in
      the repetition rate and a decrease in the rotation speed resulted in greater
      temperature increase of the exposed cornea or metal mask. CONCLUSIONS: Online
      monitoring of cornea and mask surface temperatures during excimer laser
      trephination is possible using high-speed sampling equipment. Appropriate
      adjustment of repetition rate and rotation speed may reduce thermal effects,
      especially in donor trephination.

PMID- 8871164
TI  - Slow viral replication of HSV-1 is responsible for early recurrence of herpetic
      keratitis after corneal grafting.
AB  - BACKGROUND: The presence of herpetic DNA has been shown in diseased and healthy
      corneal tissue. A clinical correlation with the activity of the disease has not
      yet been demonstrated. This study was done to evaluate the use of DNA
      amplification for HSV-1 from different sites for the clinical prognosis after
      corneal grafting. PATIENTS AND METHODS: Eighteen patients with herpetic
      keratitis, 8 patients with other forms of keratitis, and 15 patients with corneal
      disease unrelated to herpes undergoing penetrating keratoplasty were
      investigated. From these, aqueous humor was obtained at the time of surgery. The
      excised cornea was divided into three parts for paraffin embedding, 24 h tissue
      culture and preparation of minced tissue. All samples were processed for HSV-1
      glycoprotein D PCR followed by Southern blot and DNA hybridization. RESULTS: In
      the herpes group, target DNA was detected in 4/18 aqueous humor samples, 7/16
      minced tissue preparations, 6/18 explant culture fluid samples and 4/15 paraffin
      sections. In the control groups of other keratitis and non-herpetic eye disease,
      respectively, target DNA was found in 0/5 and 2/12 aqueous humor samples, 1/6 and
      0/12 minced tissue preparations, 0/8 and 0/15 explant culture fluid samples and
      in 1/6 and 1/14 paraffin sections. Five of six patients in whom herpes DNA was
      detected in the short-term tissue culture experienced an episode of herpes
      reactivation, within 4 months after transplantation, whereas only one of the
      remaining patients in all three groups did so (p = 0.0005). CONCLUSION: A slow
      viral replication may be responsible for early recurrence of herpetic keratitis
      after corneal grafting. Detection of herpetic DNA in short-term tissue cultures
      from explant tissues may help to define the patients at risk.

PMID- 8871167
TI  - The behaviour of ED1- and ED2-positive cells in the rat iris and choroid
      following penetrating keratoplasty and cyclosporin A therapy.
AB  - BACKGROUND: The presence, morphology and distribution of ED1 and ED2+ cells have
      been recently reported in detail in the uveal tissues of the rat. These cells,
      particularly those of dendritic morphology, are possibly capable of antigen
      presentation and, therefore, may play an important role in immune processes of
      uveal and other ocular tissues. Using the whole-mount technique, the distribution
      of ED1+ and ED2- cells in the rat iris and choroid was investigated following
      penetrating keratoplasty (PKP) and following treatment with cyclosporin A (CsA).
      METHODS: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN)
      donors and were randomly assigned to one of two groups: (I) operated, untreated
      (n = 24); (II) operated, CsA treated (10 mg/kg i.m.: n = 22). Four groups served
      as controls: normal LW rats (n = 13); (IV) unoperated, CsA treated (16 days'
      treatment; n = 8); (V) eight corneal sutures only, representing a simulated or
      "sham" operation (n = 4); (VI) syngeneic operated (LW to LW: n = 4). Animals of
      groups I and II were killed on the 5th, 9th and 13th postoperative days and on
      appearance of the corneal rejection (group I, day 13; Group II, day 16). Both
      eyes were enucleated, immediately fixed, and iris-choroid flat mounts were
      examined for ED1+ and ED2+ cells using APAAP immunohistochemistry. RESULTS: In
      the normal LW rat iris, ED1+ and ED2+ cells of both non-dendritic and dendritic
      morphology were observed. The placement of sutures in the cornea and PKP with or
      without treatment resulted in a reasonably regular response in both the iris and
      the choroid in the operated and partner eye. These included: (a) an increase in
      round iridal ED1+ and ED2+ cells in the operated eye and in round ED1+ cells in
      the partner eye; (b) a decrease in dendritiform ED2+ cells in the iris of the
      operated eyes as well as in the partner eye; and (c) a decrease in the
      dendritiform ED2+ cells in the choroid of the operated and partner eye. CsA
      treatment alone in unoperated animals resulted in significant decreases in the
      number of dendritiform ED1+ cells in the iris and in the dendritiform ED2+ cells
      in the choroid. CONCLUSION: Corneal transplantation in the Lewis rat results in
      responses in ED1+ and ED2+ cells in uveal tissues in both the operated eye as
      well as in the partner eye. The differences in cell behaviour supports the idea
      that distinct immune-competent cell populations are present within uveal tissues
      and that they may have differing roles in the pathological eye.

PMID- 8871168
TI  - Adhesion molecule expression in bullous keratopathy.
AB  - BACKGROUND: Adhesion molecules may play an important role in the pathogenesis of
      bullous keratopathy. METHODS: The expression of the integrin VLA-beta 1, alpha
      subunits of the beta 2-integrins LFA-1, Mac-1, and p150,95, the members of the
      immunoglobulin family ICAM-1 and VCAM-1, and the selectin ELAM-1 on corneas with
      bullous keratopathy (BK) secondary to intraocular surgery was studied
      immunohistochemically using an APAAP method. RESULTS: In the corneas with BK (in
      contrast to normal corneas), a downregulation of VLA-beta 1 was observed
      throughout the corneal tissues, particularly on the epithelial layer where bullae
      occurred; ICAM-1 was induced on epithelial membranes in both BK and inflamed
      corneas; and the expression of beta 2-integrins, VCAM-1 and ELAM-1 was
      upregulated in some specimens with remaining endothelial cells. CONCLUSION: The
      results show that the investigated adhesion molecules may participate in the
      pathogenesis of BK. The decrease in VLA-beta 1 in patients with BK may be an
      important factor in the occurrence and development of recurrent bullae; the
      induced ICAM-1 may recruit beta 2-integrin-positive leukocytes into the
      epithelial layer, thus aggravating epithelial damage; and beta 2-integrins and
      VCAM-1 may play a role in endothelial injury and decompensation.

PMID- 8871169
TI  - Optic disc shape in glaucoma.
AB  - BACKGROUND: This study was performed to evaluate the shape of the optic disc in
      glaucoma. METHODS: We examined morphometrically color stereo optic disc
      photographs of patients with primary open-angle glaucoma (n = 804), secondary
      open-angle glaucoma (n = 130), normal-pressure glaucoma (n = 75), and high myopia
      combined with open-angle glaucoma (n = 33), visually normal subjects (n = 421),
      and nonglaucomatous subjects with high myopia (n = 36). The optic disc form was
      determined by the ratio of the minimal to the maximal disc diameter, the ratio of
      the horizontal to the vertical disc diameter, the angle between the maximal disc
      diameter and the horizontal, and a calculated form factor. RESULTS: In the normal
      eyes, the ratios and the form factor varied interindividually by less than 1:2.
      For a myopic refractive error of less than -8 D, the normal eyes and the glaucoma
      eyes did not differ significantly (P > 0.20) in their slightly vertically oval
      optic disc shape. Within the primary open-angle glaucoma group, the optic disc
      shape was not correlated with the neuroretinal rim area and the mean perimetric
      defect, either interindividually or in an intraindividual bilateral comparison.
      In the highly myopic group, the optic disc was significantly more ovally
      configurated, more obliquely orientated, and larger than in any other group.
      CONCLUSIONS: In contrast to the size of the optic nerve head, the shape of the
      optic disc does not show pronounced interindividual variability in eyes with a
      myopic refractive error of less than -8 D. With highly myopic eyes excluded, the
      optic disc shape as single variable is not markedly important for pathogenesis,
      early diagnosis and differential diagnosis of the glaucomas.

PMID- 8871170
TI  - Quadrant pattern ERG with SLO stimulation in normals and glaucoma patients.
AB  - BACKGROUND: The pattern ERG (PERG) is one of the promising methods for
      investigation of glaucoma and may detect it at an early stage. The purpose of
      this study was to test the usefulness of the scanning laser ophthalmoscope (SLO)
      as a stimulator for evoking quadrant PERGs under visual control in normal and
      glaucoma eyes. METHODS: The helium-neon laser of a Rodenstock SLO was used for
      quadrant stimulation (18 degrees x 29 degrees pattern size), while an infrared
      laser visualized the eye's fundus. Steady-state pattern-reversal ERGs were
      recorded in response to stripe patterns (8.33 Hz, 0.5 cycles/deg) in four retinal
      quadrants. Corresponding visual field defects were determined with the Octopus
      perimeter (G1, peridata). The subjects were 28 controls and 34 glaucoma patients
      with visual field losses and papillometric defects. RESULTS: Amplitudes of nasal
      retinal areas (which include the blind spot) are smaller than those of temporal
      ones, and temporal lower responses are the largest. PERG amplitudes of all
      quadrants are significantly reduced in glaucoma (sensitivity 82%, specificity
      80%). The differences between upper and lower quadrant PERGs are correlated with
      the differences between localized visual field defects of the same areas, (r =
      0.46, P = 0.02). CONCLUSIONS: The study demonstrates the feasibility of the SLO
      system for evoking localized PERG in normals and patients and shows the reduction
      of quadrant ERG amplitudes in glaucoma using the laser system.

PMID- 8871171
TI  - Color axis evaluation of the Farnsworth Munsell 100-hue test in primary open
      angle glaucoma and normal-pressure glaucoma.
AB  - BACKGROUND: It was the aim of the present study to analyze a separate color-axis
      evaluation of the Farnsworth Munsell 100-hue test (FM 100) in primary open-angle
      glaucoma (POAG) and normal pressure glaucoma (NPG). PATIENTS AND METHODS: One eye
      of each of 112 individuals (age 35-65 years, visual acuity > 20/28, myopia < -7.5
      D) was included. The groups consisted of 62 normal subjects and 50 glaucoma
      patients (33 POAG and 17 NPG). We evaluated the FM 100 overall error score and
      the error scores of the protan, deutan and tritan axes. The results were compared
      with perimetric (Octopus G1 mean defect) and morphometric data of the optic disc.
      RESULTS: All error scores were significantly higher in the glaucoma group than in
      the normal group. In an age-related evaluation, differences were significant in
      age groups above 45 years. No significant differences were found between the POAG
      and NPG groups. The sensitivity of the overall score to identify glaucoma was 62%
      (specificity 80%). In the glaucoma group the overall score and the protan score
      increased significantly with the mean defect (r > 0.3, P < 0.01). Several scores
      increased slightly with decreasing neuroretinal rim area, but not on a
      significant level. Separate color-axis evaluations did not show any stronger
      correlations and did not reveal any differences between POAG eyes and NPG eyes.
      This was true even for the tritan axis error. CONCLUSIONS: Although FM 100 error
      scores are higher in glaucoma eyes and increase with glaucomatous damage, they do
      not separate well. In the sample of this study, separate color-axis evaluation
      did not improve the diagnostic value. With the FM100 a different pattern of color
      vision defects in POAG and NPG eyes could not be detected.

PMID- 8871172
TI  - Spherophakia, nanophthalmia, hypoplastic ciliary body and glaucoma in
      brachydactyly-associated syndromes.
AB  - Three juvenile patients showing a systemic disorder associated with small
      stature, brachydactyly and glaucoma were discovered to have spherophakia and a
      nanophthalmic axial length of the eye between 20.29 and 21.26 mm. According to
      clinical and radiological criteria only one patient was classified as having
      Marchesani syndrome; one patient suffered from an acrofacial disorder, and the
      third displayed typical ocular signs of Rieger syndrome. Pupillary block
      mechanism had led to glaucoma in all three patients. Despite iridectomy and
      trabeculotomy, two of them had unregulated intraocular pressure (IOP) and showed
      partial angleblock by progressive anterior synechiae after surgery.
      Ultrasonographic biomicroscopy revealed in all cases considerable hypoplasia of
      the ciliary body. We conclude that the clinical combination of spherophakia and
      brachydactyly is not necessarily limited to Marchesani syndrome. In the wide
      range of brachydactyly-associated syndromes an ophthalmic examination should
      always be performed in order to rule out ocular complications such as
      spherophakia and secondary glaucoma. We could not confirm Marchesani's hypothesis
      of a hyperplastic ciliary body in the spherophakia-brachydactyly syndrome,
      considering our nanophthalmic eyes. Pressure-reducing surgery in eyes with
      spherophakia and nanophthalmia seems to run a high risk of inducing an extensive
      formation of anterior synechiae.

PMID- 8871173
TI  - Acetazolamide affects performance on the Nagel II anomaloscope.
AB  - BACKGROUND: Recent reports have indicated that acetazolamide alters human
      electroretinograms. We wished to determine the effects of administering
      acetazolamide on performance on the Nagel II anomaloscope. METHODS: We tested 15
      subjects matches of blue-green light to a mixture of blue and green lights
      (luminance match) on a Nagel type II anomaloscope 2.5 h after ingesting 500 mg of
      acetazolamide or a placebo. RESULTS: The mean of the luminance settings for the
      subjects was 54.4 for the placebo condition and 58.5 for the acetazolamide
      condition. The mean difference of 4.1 was statistically significant, indicating
      that following ingestion of acetazolamide subjects were less sensitive to a blue
      green light. In two supplementary experiments we tested (1) a second group of
      four normal subjects using the Nagel type II anomaloscope and (2) the previously
      untreated eyes of four patients with primary open-angle glaucoma before and after
      placing them on acetazolamide therapy. In both groups, more blue-green light was
      needed to make the match after ingestion of acetazolamide. CONCLUSIONS:
      Acetazolamide alters the sensitivity of one or more cone populations, probably
      the carbonic anhydrase-containing cones. The sensitivity loss is reversible and
      does not appear to be clinically significant. However, the results suggest that
      patients administered acetazolamide should be excluded from studies which compare
      the color vision of glaucomatous patients to that of normals.

PMID- 8871174
TI  - Aqueous humor dynamics in rats.
AB  - BACKGROUND: In order to determine normal outflow facility and aqueous humor
      production values in Lewis rats, we established methods of measuring aqueous
      humor dynamics in this animal. METHODS: Outflow facility was determined using
      anterior chamber infusion with constant pressure. Aqueous humor production was
      determined by a technique of dilution with FITC-albumin. RESULTS: The mean
      outflow facility was 0.044 +/- 0.01 microliter/min/mmHg. Rats weighing less than
      300 g had lower values than did rats weighing more than 300 g (0.034 +/- 0.006
      microliter/min/mmHg vs 0.050 +/- 0.015 microliter/min/mmHg, P = 0.009). The mean
      aqueous humor production was 0.350 +/- 0.110 microliter/min. The turnover rate of
      aqueous humor production per minute was 2.23%. CONCLUSIONS: Anterior chamber
      infusion with constant pressure and the FITC-albumin method allow measurement of
      the outflow facility and aqueous humor production in Lewis rats. These methods
      may be useful in assessing aqueous humor dynamics when rats are used as a
      glaucoma model.

PMID- 8871175
TI  - Effects of Er:YAG laser trabecular ablation on outflow facility in cadaver
      porcine eyes.
AB  - BACKGROUND: Mid-infrared laser technology opens new perspectives in experimental
      glaucoma surgery. The aim of this study was to establish the effectiveness of
      Er:YAG laser photoablation of the trabecular meshwork in increasing outflow
      facility in cadaver porcine eyes. METHODS: Eye cups of 20 freshly enucleated
      cadaver porcine eyes were fixed in an anterior segment perfusion system,
      measuring outflow facility under constant pressure conditions (7-13 mmHg) over a
      period of 45 min. Trabecular ablation was performed using a pulsed Er:YAG (2.94
      microns) laser. Radiation was delivered in a single 4-mJ pulse of 200
      microseconds duration by means of an articulated zirconium fluoride optical fibre
      and a 320-microns quartz-fibre tip. RESULTS: Er:YAG laser treatment yielded
      reproducible ablation areas confined to the trabecular meshwork, with a diameter
      corresponding to that of the fibre tip. Collateral thermal damage extended up to
      a depth of 30 microns. Outflow facility measurements revealed an increase (mean
      +/- SD) from 0.128 +/- 0.041 microliter min-1 mmHg-1 in control eyes (n = 11) to
      0.308 +/- 0.093 microliter min-1 mmHg-1 in treated ones (n = 9). CONCLUSION:
      Application of the photoablative Er:YAG laser technique in non-fistulating
      trabecular surgery produces patent trabecular perforation with minimal collateral
      tissue damage and effects a significant reduction (79%) in outflow resistance.

PMID- 8871176
TI  - Histopathological evaluation of retinal damage during intraocular hypertension in
      rabbit: involvement of ganglion cells and nerve fiber layer.
AB  - BACKGROUND: Current clinical tests do not detect glaucomatous signs until the
      onset of substantial retinal damage. Therefore animal models are required to
      investigate the very early histopathological alterations in glaucoma disease. We
      used an experimental model of intraocular hypertension to compare early changes
      in retinal ganglion cell (RGC) density with the thickness of the nerve fiber
      layer (NFL). METHODS: Methylcellulose 2% was injected into the anterior chamber
      of 18 eyes of 18 New Zealand albino rabbits. Intraocular pressure was measured 6
      h after the injection and thenceforth once a day using a Shiotz tonometer.
      Histopathological analysis was performed on days 4, 10, and 15 following the
      induction of hypertension (six eyes for each group). Sections from the upper
      temporal retina were stained with hematoxylin-eosin and immunohistochemically
      using a polyclonal antibody PGP 9.5 to identify RGC. An image analysis system was
      used to evaluate the RGC and the thickness of the NFL. RESULTS: We observed a
      significant increase in intraocular pressure until the end of the experiment.
      Histological analysis showed, after 10 days of ocular hypertension, a significant
      decrease in RGC density (P < 0.05) and a significant increase (P < 0.05) in glial
      cell density. We found a significant correlation between RGC loss and cell area
      at 4 days (P < 0.01; Cc = 0.86) and at 10 days (P < 0.002; Cc = 0.91) of
      intraocular hypertension. We did not observe a significant decrease in the NFL
      thickness until 10 days of intraocular hypertension. CONCLUSIONS: Our study
      confirms the size-dependent RGC loss during intraocular hypertension and shows no
      early decrease in NFL thickness.

PMID- 8871177
TI  - Effect of fibrostatin C, an inhibitor of prolyl 4-hydroxylase, on collagen
      secretion by human Tenon's capsule fibroblasts in vitro.
AB  - PURPOSE: To investigate the effect of fibrostatin C, a prolyl 4-hydroxylase (PH)
      inhibitor produced by Streptomyces catenulae subsp. griseospora, on type I
      collagen secretion by human Tenon's capsule fibroblasts (TCFs) in vitro, as an
      indication of the potential therapeutic efficacy of this compound in antifibrotic
      therapy after glaucoma filtering surgery. METHODS: The concentrations of type II
      procollagen COOH-terminal peptide (PIP) in culture medium or cell lysate were
      determined by immunoassays. For comparison with its effect on PIP secretion, we
      determined the effects of the agent on the secretion of other peptides, including
      laminin, vitronectin receptor, and a metalloproteinase inhibitor. The expression
      of collagens I and III, fibronectin, and PH by TCFs was examined by
      immunohistochemistry, and cellular ultrastructure was evaluated by transmission
      electron microscopy. RESULTS: Fibrostatin C (50 microM) significantly reduced the
      concentration of PIP in culture medium and increased its concentration in the
      cell lysate in a dose-dependent manner, but it had no effect on the secretion of
      other peptides. Cell viability and proliferation were not affected by fibrostatin
      C. Fibrostatin C also increased the number of cytoplasmic granules immunoreactive
      with antibodies to collagen I or III, but had no effect on fibronectin or PH
      immunoreactivity. Ultrastructurally, cisternae of the endoplasmic reticulum were
      dilated in fibrostatin C-treated TCFs, consistent with the retention of
      underhydroxylated collagen precursors in this organelle. CONCLUSIONS: Fibrostatin
      C inhibits the secretion of type I collagen by cultured TCFs. This agent may thus
      prove therapeutically beneficial for inhibiting the excess fibrosis in the wound
      of filtering surgery.

PMID- 8871178
TI  - Evaluation of a new E-optotype chart for measuring contrast sensitivity.
AB  - BACKGROUND: Clinical examinations of the contrast sensitivity (CS) are currently
      made by one-trial measurements of a restricted number of spatial frequencies
      around the peak of the CS function (CSF). These methods do not allow calculation
      of the confidence intervals of the single measurements, thus preventing examiners
      from evaluating the reliability of their data. We elaborated a new method of CS
      measurement at the peak of the CSF, aiming at economical clinical applicability
      together with enhanced reliability. Moreover, we tried to establish lower limits
      of normal CS that would allow classification of low test results as pathological.
      METHODS: A chart containing six columns of E optotypes of constant size and
      decreasing contrast (from about 16% to 0.5%) was used to perform six-fold
      contrast threshold determination (method of descending limits, forced choice).
      Optotype dimensions are intended to measure the CS at spatial frequencies
      corresponding to 3 and 6 cycles per degree (c/deg). The reference values were
      defined by testing 61 normal subjects: 31 "young" (16-35 years) and 30 "old" (56
      81 years). RESULTS: The mean logCS found in the young group was 2.07 +/- 0.086 SD
      for 3 c/deg and 1.94 +/- 0.154 SD for 6 c/deg, while in the old group the mean
      logCS was 1.88 +/- 0.095 SD and 1.74 +/- 0.118 SD respectively. CONCLUSION: This
      simple method of measuring CS can provide a single CS value together with a
      confidence interval for the individual patient, thus allowing evaluation of
      measurement reliability.

PMID- 8871179
TI  - Recurrent intrascleral cyst after strabismus surgery.
AB  - BACKGROUND: Intrascleral epithelial inclusion cysts have been described after
      ocular trauma, scleral buckling and strabismus surgery. They are usually small,
      asymptomatic and located anteriorly. CASE REPORT: The clinical history of a 9
      year-old girl who developed a huge epi- and retrobulbar intrascleral cyst in both
      the upper and the lower nasal quadrants after multiple strabismus operations is
      described. RESULTS: Surgical resection of the cyst wall was twice unsuccessful.
      Drainage of the cyst, followed by the injection of tetracycline (30 mg/ml) in the
      cyst site, led to complete recovery. CONCLUSION: Recurrent posteriorly located
      intrascleral cyst can occur after strabismus surgery. Therapy consisting of
      drainage combined with intrascleral administration of tetracycline solution (30
      mg/ml) to induce sclerodesis appeared to be effective during a 2-year follow-up
      period.

PMID- 8871180
TI  - Crystallin composition of human cataractous lens may be modulated by protein
      glycation.
AB  - BACKGROUND: This study was designed to establish whether increased glycation of
      human crystallins could be related to an increased susceptibility to aggregation
      and insolubilization. The study was focused particularly on the glycation levels
      and composition of low-molecular-weight (LMW) peptides present in human
      cataractous lenses. METHODS: Lens crystallins from the water-soluble fraction
      were separated on a preparative scale by gel filtration. Each crystallin was
      purified and its glycation level evaluated as furosine content. The peptides were
      further purified by reverse-phase chromatography. The amino acid composition of
      each of these peptides was also determined by RP-HPLC using PITC pre-column
      derivatization. RESULTS: The high-molecular-weight (HMW), alpha L-crystallin and
      LMW crystallins from diabetic patients present high furosine content. LMW
      peptides were shown to constitute a heterogeneous population of three major
      peptides with a lysine content similar to that observed for native crystallins.
      These peptides were shown to present glycation levels ten times higher than those
      observed for the crystallins. Glycated proteins from insoluble fraction were
      found to be mostly urea soluble and were present at higher concentration in
      diabetic cataracts. CONCLUSIONS: LMW peptides are suggested to play a major role
      in protein aggregation and insolubilization, probably via a mechanism involving
      protein glycation. This process seems to be particularly relevant to diabetic
      cataract development.

PMID- 8871181
TI  - Inward and outward permeability of the blood-retinal barrier in experimental
      myopia.
AB  - BACKGROUND: To investigate the pathophysiology of the retina in myopia, vitreous
      fluorophotometry was used to evaluate the permeability of the blood-retinal
      barrier (BRB) in experimentally induced myopia in cynomolgus monkeys. METHODS:
      Five animals underwent unilateral eyelid suturing. The suture was removed
      temporarily at 3, 10, 16, 28 and 36 months, and the dioptric power and axial
      length were measured in both eyes. Vitreous fluorophotometry was performed before
      and 60 min after intravenous injection of fluorescein-Na. BRB inward permeability
      (P(in)) was determined by a computer simulation method. At 36 months, fluorescein
      Na was injected into the vitreous cavity, and the intraocular fluorescence was
      measured. BRB outward permeability (P(out)) was determined by the computer
      simulation method. RESULTS: Significant myopia developed by 10 months after
      suturing and progressed thereafter. Starting at 10 months, the P(in) of sutured
      eyes increased significantly compared with control fellow eyes, and the increase
      continued throughout the observation period. At 36 months, the BRB P(out) was
      significantly lower (P < 0.05) in the myopic than in the emmetropic fellow eyes,
      suggesting decreased active transport mechanisms at the BRB in myopia.
      CONCLUSION: Our study demonstrated, for the first time, abnormal permeability of
      the BRB in myopic monkey eyes. Such abnormal permeability may play an important
      role in the development in human myopes of retinal and vitreous changes such as
      retinal detachment. Thus, simply correcting refractive errors surgically may not
      represent a cure for myopia. Patients who have had refractive surgery to correct
      myopia should also be closely followed up by vitreo-retinal specialists to manage
      vitreo-retinal disorders in originally myopic eyes.

PMID- 8871182
TI  - Neuropeptide Y, the hypothalamus and the regulation of energy homeostasis.
AB  - Neuropeptide Y (NPY) neurones in the arcuate nucleus of the rodent hypothalamus
      may play a key role in responding to reductions in body energy stores with
      appropriate changes in energy homeostasis, namely an increase in food-seeking
      behaviour and hyperphagia, together with a reduction in heat production by brown
      adipose tissue. These adaptive responses are mimicked by the injection of NPY
      into the main sites of projection of the NPY neurones, and animals that are
      threatened by energy deficits (e.g. through starvation or insulin-deficient
      diabetes) show increased activity of these neurones. Genetically obese rodents
      also show hyperactivity of the NPY neurones, which is inappropriate to their
      energy needs and may contribute to their hyperphagia, reduced energy expenditure
      and excessive weight gain. The NPY neurones may be inhibited by insulin and
      leptin, which may both serve as signals of peripheral fat mass. Ultimately,
      characterization of the specific "feeding' receptors which mediate NPY's central
      effects on energy homeostasis may provide opportunities for designing drugs to
      manipulate and appetite and energy balance in man, notably obesity and the
      cachexia commonly associated with malignancy and chronic infection.

PMID- 8871183
TI  - Responses of somatostatin, beta-endorphin and dynorphin A to a glucose load in
      two groups of women with polycystic ovarian syndrome.
AB  - To investigate the relationship between elevated LH, hyperinsulinemia and
      neuropeptides in polycystic ovarian syndrome (PCOS), we measured the endogenous
      levels of insulin, somatostatin (SS), beta-endorphin (beta-EP) and dynorphin A
      (Dyn A) before and after a glucose load in three groups: group 1 (LH/ FSH > or =
      3, n = 30); group 2 (LH/FSH < 3, n = 25), and controls (n = 15). In the basal
      state, significantly negative correlations were found between LH and SS (r = 
      0.51, p < 0.05) in group 1 and between LH and beta-EP (r = -0.49, p < 0.05) in
      group 2. After a glucose load, PCOS women had greater beta-EP and Dyn A responses
      in group 1 and impaired SS response in group 2 as compared with the control. The
      data suggest endogenously lower SS, higher beta-EP and Dyn A may contribute to
      the elevation of LH and insulin secretions in PCOS.

PMID- 8871184
TI  - An investigation into the lability of the bioactivity of human growth hormone
      using the ESTA bioassay.
AB  - We compared the bioactivity attributable to human growth hormone (hGH) in serum
      samples, determined at the time of their collection, with that after storage for
      2-18 months at -20 degrees C. The samples were obtained from volunteers and
      patients who underwent provocative tests of hGH secretion, and the bioactivity
      was determined in the ESTA bioassay, which is based upon the use of Nb2 cells. We
      report that, in some subjects, the bioactivity of samples collected at the
      response peaks deteriorated on storage for as little as 2 months. The decrease in
      hGH bioactivity was systematic in that it consistently declined so as to approach
      the values initially determined by an immunoassay (Hybritech IRMA). This
      differential lability was a characteristic of the peak samples, and was not
      observed for either samples collected before and after the peaks of hGH secretion
      or for purified preparations of hGH which were subjected to a range of
      freeze/thaw and storage regimens. We suggest that this unusual lability is
      indicative of transient shifts in the spectrum of the variants of hGH which are
      present in the circulation following stimulation by provocative agents. This
      study emphasises the need to minimise the risk of introducing storage artefacts
      in investigations into the responses of hGH to provocation.

PMID- 8871186
TI  - Differentiation of normal male prepuberty and hypogonadotrophic hypogonadism
      using an ultrasensitive luteinizing hormone assay.
AB  - BACKGROUND AND OBJECTIVE: To assess how the Delfia time-resolved
      immunofluorometric assay can most conveniently and economically be used to
      differentiate normal prepuberty from complete idiopathic hypogonadotrophic
      hypogonadism (IHH, Kallmann's syndrome). SUBJECTS: 42 prepubertal boys aged 8.06
      14.1 years and 11 adult male patients with IHH. DESIGN AND MEASUREMENTS: Blood
      samples were withdrawn at 20-min intervals for 8 h from 23.00 to 07.00. Samples
      from the 6 h commencing 1 h after sleep onset were analysed for LH by Delfia.
      RESULTS: Mean LH over this 6-hour period discriminated between IHH and normal
      prepuberty after the age of 12.5 years (no IHH subject > 0.31 U/l, no prepubertal
      subject < 0.33 U/l). The maximum hourly mean LH value for each subject gave a
      greater degree of mutual exclusivity (no IHH subject > 0.45 U/l, no prepubertal
      subject < 0.50 U/l). CONCLUSION: Kallmann's syndrome patients can be
      distinguished from prepubertal boys aged 12.5 years or over by blood sampling
      every 20 min for 6 h, commencing 1 h after sleep onset. The pooling of these
      samples into six 1-hour samples and subsequent Delfia assay will yield six 1-hour
      mean LH concentrations for each subject. The highest of these six concentrations
      will give a value with mutual exclusivity between the two groups.

PMID- 8871185
TI  - Atrial natriuretic peptide in renal transplantation.
AB  - Factors related to atrial natriuretic peptide (alpha-ANP) regulation and its
      potential impact on excretory transplant function were examined in a prospective
      cohort study of 20 patients with end-stage renal disease over 21 days after
      allogenic kidney transplantation. Depending on posttransplant graft function,
      patients were separated into those with primary renal function (PF group, n = 10)
      and posttransplant acute renal failure (ARF group, n = 10). ANP concentrations
      were markedly elevated in both PF and ARF immediately after renal
      transplantation, even when compared with the pretransplant dialysis phase (PF
      group: 939 +/- 467 pg/ml; ARF group: 648 +/- 306 pg/ml, on 3rd postoperative day;
      "normals': 72 +/- 35 pg/ml). Whilst ANP levels were persistently elevated in
      patients with acute renal failure, there was a steady decrease in plasma
      concentrations in patients with primary renal function (PF: 270 +/- 122 pg/ml on
      21st day). ANP concentration correlated with endogenous creatinine clearance (rz
      = 0.56, p < 0.01, PF group). Moreover, there was a greater correlation between
      ANP levels and postoperative hydration status, measured as central venous
      pressure or the difference from predialysis dry weight (rz = 0.79 and rz = 0.74,
      p < 0.01, PF group). Systolic blood pressure was also positively correlated with
      ANP concentrations. Together, these factors accounted for a total correlation
      coefficient of r = 0.87 (p < 0.001) in multiple regression analysis. No
      significant relation was found between plasma ANP levels and total or fractional
      sodium excretion or free water clearance. With the restoration of renal function
      most vasoactive hormones (renin-aldosterone system, catecholamines, vasopressin)
      decreased towards normal values, whilst ANP plasma concentrations remained
      elevated.

PMID- 8871187
TI  - Self-concept before and after two years of growth hormone treatment in
      intrauterine growth-retarded children.
AB  - The objective of this study was to assess self-concept in children with short
      stature after intrauterine growth retardation (IUGR), before and after 2 years of
      growth hormone (hGH) treatment. We assessed 25 children before treatment, and 40
      children after a 2-year treatment period. Seventeen of the 25 children of whom we
      had pretreatment data, were reassessed after 2 years of hGH treatment. All
      children had a birth length below the 3rd percentile, and did not show catch-up
      growth (current height < P3). We compared the self-concept measures (Self
      Perception Profile for Children; SPPC) of the IUGR group with similar measures of
      a Dutch school sample. Four of the six SPPC mean scale scores of the IUGR group
      prior to treatment were significantly lower than mean scores of the school
      sample. Mean-scale scores of the group children, assessed after 2 years of hGH
      treatment, did not differ significantly from those of the school sample. In the
      group of 17 children who were assessed before as well as after 2 years of
      treatment, the mean scale scores of 'social acceptance' and 'general self-worth'
      were significantly higher at the second assessment (t = -5.93, p < 0.001 and t = 
      4.36, p < 0.001, respectively). From the present study we can hypothesize that
      short stature after IUGR and a low self-concept are related.

PMID- 8871188
TI  - Androgens and their role in skeletal homeostasis.
AB  - Androgens are needed during the entire lifespan of the male skeleton -at least in
      the rat. Indeed, in aged nongrowing male rats, androgens are necessary for the
      maintenance of skeletal integrity. In these animals, androgen deficiency results
      in a menopause-like acceleration of bone turnover and bone loss which are
      presented by androgen replacement. In the growing skeleton, androgens probably
      have a twofold effect. Not only neonatal androgens but also pubertal androgen
      secretions are needed for normal skeletal growth and modeling in order to reach
      full size (cortical) bone mass. Moreover, androgens are not only necessary for
      the (cortical) bone mass but also for the maintenance of cancellous bone
      compartment during growth, at least in androgen-deficient rats. However, both
      animal experiments and recent human data suggest that at least part of the
      complex skeletal effects of androgens may depend on the aromatization of
      androgens into estrogens.

PMID- 8871189
TI  - Layer I neurons of rat neocortex. I. Action potential and repetitive firing
      properties.
AB  - 1. Whole cell patch-clamp techniques, combined with direct visualization of
      neurons, were used to study action potential (AP) and repetitive firing
      properties of layer I neurons in slices of rat neocortex. 2. Layer I neurons had
      resting membrane potentials (RMP) of -59.8 +/- 4.7 mV (mean +/- SD) and input
      resistances (RN) of 592 +/- 284 M Omega. Layer II/III pyramidal neurons had RMPs
      and RNs of -61.5 +/- 5.6 mV and 320 +/- 113 M omega, respectively. A double
      exponential function was needed to describe the charging curves of both neuron
      types. In layer I neurons, tau(0) was 45 +/- 22 ms and tau(1) was 5 +/- 3.3 ms
      whereas in layer II/III pyramidal neurons, tau(0) was 41 +/- 11 ms and tau(1) was
      3 +/- 2.6 ms. Estimates of specific membrane resistance (Rm) for layer I and
      layer II/III cells were 45 +/- 22 and 41 +/- 11 k omega cm2, respectively (Cm was
      assumed to be 1 microF/cm2). 3. AP threshold was -41 +/- 2 mV in layer I neurons.
      Spike amplitudes, measured from threshold to peak, were 90.6 +/- 7.7 mV. AP
      durations, measured both at the base and half maximal amplitude, were 2.5 +/- 0.4
      and 1.1 +/- 0.2 ms, respectively. AP 10-90% rise and repolarization times were
      0.6 +/- 0.1 and 1.1 +/- 0.2 ms, respectively. In layer II/III pyramidal neurons,
      AP threshold was -41 +/- 2.5 mV and spike amplitude was 97 +/- 9.7 mV. AP
      duration at base and half maximal amplitude was 5.4 +/- 1.1 ms and 1.8 +/- 0.2
      ms, respectively. AP 10-90% rise and decay times were 0.6 +/- 0.1 ms and 2.8 +/-
      0.6 ms, respectively. 4. Layer I neurons were fast spiking cells that showed
      little frequency adaptation, a large fast afterhyperpolarization (fAHP), and no
      slow afterhyperpolarization (sAHP). Some cells had a medium
      afterhyperpolarization (mAHP) and a slow afterdepolarization (sADP). All
      pyramidal cells in layer II/III and "atypical" pyramidal neurons in upper layer
      II showed regular spiking behavior, prominent frequency adaptation, and marked
      sAHPs. 5. In both layer I neurons and layer II/III pyramidal neurons, changes in
      membrane potential did not greatly alter AP properties. The duration of APs
      evoked from -50 to -60 mV was only slightly longer, from -80 to -90 mV. The
      latency to first spike also was not solely dependent on membrane potential. 6.
      During repetitive firing, APs broadened in both layer I neurons and layer II/III
      pyramidal neurons. This was most prominent in pyramidal cells. Broadening was
      dependent on spike frequency and appeared to result from partial inactivation of
      both outward potassium and inward sodium currents. 7. In layer I neurons,
      removing Ca2+ from the bathing solution slightly prolonged spike duration and
      modestly increased AP firing frequency. These results indicate minimal
      involvement of Ca2+-dependent K+ currents in AP repolarization. fAHPs were
      reduced whereas sADPs were abolished. In layer II/III pyramidal neurons, removing
      Ca2+ reduced or blocked mAHPs and sAHPs and decreased or abolished frequency
      adaptation. 8. Low concentrations (50 microM) of 4-aminopyridine (4-AP) prolonged
      APs and induced burst-like firing in layer I neurons. In the presence of 4-AP,
      the spiking behavior of layer I neurons resembled that of regular spiking layer
      II/III pyramidal cells. At high concentrations (4 mM), 4-AP could induce a
      delayed depolarization (DD) after each spike in layer I neurons and in a minority
      of pyramidal neurons. 9. All layer I neurons had a prominent fAHP that was absent
      or very small in layer II/III pyramidal neurons. fAHP amplitude was inversely
      related to AP duration. The reduction of fAHPs by 4-AP or during repetitive
      firing was accompanied by AP prolongation, suggesting that the current underlying
      fAHP played an essential role in AP repolarization. The fAHP of layer I neurons
      could be effectively blocked by 4-AP but only slightly reduced by removing Ca2+
      from bathing solution, indicating that the fAHP was mediated primarily by a
      voltage-dependent transient outward current.(ABSTRACT TRUNCATED)

PMID- 8871190
TI  - Layer I neurons of the rat neocortex. II. Voltage-dependent outward currents.
AB  - 1. Whole cell patch-clamp techniques, combined with direct visualization of
      neurons, were used to study voltage-dependent potassium currents in layer 1
      neurons and layer II/III pyramidal cells. 2. In the presence of tetrodotoxin,
      step depolarizations evoked an outward current. This current had a complex
      waveform and appeared to be a composite of early and late components. The early
      peak of the composite K+ outward current was larger in layer I neurons. 3. In
      both layer I and pyramidal cells, the composite outward K+ current could be
      separated into two components based on kinetic and pharmacological properties.
      The early component was termed I(A) because it was a transient outward current
      activating rapidly and then decaying. I(A) was more sensitive to blocking by 4
      aminopyridine (4-AP) than tetraethylammonium (TEA). The second component, termed
      the delayed rectifier or I(DR), activated relatively slowly and did not decay
      significantly during a 200-ms test pulse. I(DR) was insensitive to blocking by 4
      AP at concentrations up to 4 mM and blocked by > 60% by 40-60 mM TEA. 4. I(A)
      kinetics were examined in the presence of 40-60 mM TEA. Under these conditions,
      I(A) began to activate between -40 and -30 mV. Half-maximal activation occurred
      around 0 mV. In both layer I and pyramidal cells, the half-inactivation potential
      (Vh-inact) was around or more positive than -50 mV. At -60 mV, > 70% of I(A)
      conductance was available. I(A) decayed along a single exponential time course
      with a time constant of approximately 15 ms. This decay showed little voltage
      dependence. 5. In both layer I and pyramidal cells, I(DR) was studied in the
      presence of 4 mM 4-AP to block I(A) and in saline containing 0.2 mM Ca2+ and 3.6
      mM Mg2+ to reduce contributions from Ca2+-dependent K+ currents. Under these
      conditions, I(DR) began to activate at -35 to -25 mV with Vh-act of 3.6 +/- 4.5
      mV (mean +/- SD). The 10-90% rise time of I(DR) was 15 ms at 30 mV. At 2.2 ms
      after the onset of the command potential to +30 mV, I(DR) could reach a
      significant amplitude (approximately 1.5 nA in layer I neurons and 2.2 nA in
      pyramidal cells depending on the cell size). When long test pulses (> or = 1,000
      ms) were used, a decay time constant approximately 800 ms at +40 mV was observed.
      In both layer I and pyramidal cells, steady state inactivation of I(DR) was
      minimal. 6. These results indicate that I(A) and I(DR) are the two major
      hyperpolarizing currents in layer I and pyramidal cells. The kinetics and
      pharmacological properties of I(A) and I(DR) were not significantly different in
      fast-spiking layer I neurons and regular-spiking layer II/III pyramidal cells.
      The relatively positive activation threshold (more than or equal to -40 mV) of
      both I(A) and I(DR) suggest that they do not play a role in neuronal behavior
      below action potential (AP) threshold and that their properties are more suitable
      to repolarize AP. The greater density of I(A) in layer I neurons appears
      responsible for fast spike generation.

PMID- 8871191
TI  - Subthreshold membrane resonance in neocortical neurons.
AB  - 1. Using whole cell recording techniques, we studied subthreshold and
      suprathreshold voltage responses to oscillatory current inputs in neurons from
      the sensorimotor cortex of juvenile rats. 2. Based on firing patterns, neurons
      were classified as regular spiking (RS), intrinsic bursting (IB), and fast
      spiking (FS). The subthreshold voltage-current relationships of RS and IB neurons
      were rectifying whereas FS neurons were almost ohmic near rest. 3. Frequency
      response curves (FRCs) for neurons were determined by analyzing the frequency
      content of inputs and outputs. The FRCs of most neurons were voltage dependent at
      frequencies below, but not above, 20 Hz. Approximately 60% of RS and IB neurons
      had a membrane resonance at their resting potential. Resonant frequencies were
      between 0.7 and 2.5 Hz (24-26 degrees C) near -70 mV and usually increased with
      hyperpolarization and decreased with depolarization. The remaining RS and IB
      neurons and all FS neurons were nonresonant. 4. Resonant neurons near rest had a
      selective coupling between oscillatory inputs and firing. These neurons
      selectively fired action potentials when the frequency of the swept-sine-wave
      (ZAP) current input was near the resonant frequency. However, when these neurons
      were depolarized to -60 mV, spike firing was associated with many input
      frequencies rather than selectively near the resonant frequency. 5. We examined
      three subthreshold currents that could cause low-frequency resonance: IH, a slow,
      hyperpolarization-activated cation current that was blocked by external Cs+ but
      not Ba2+; IIR, an instantaneously activating, inwardly rectifying K+ current that
      was blocked by both Cs+ and Ba2+; and INaP, an quickly activating, inwardly
      rectifying persistent Na+ current that was blocked by tetrodotoxin (TTX). Voltage
      clamp experiments defined the relative steady state activation ranges of these
      currents. IIR (activates below -80 mV) and INaP (activates above -65 mV) are
      unlikely to interact with each other because their activation ranges never
      overlap. However, both currents may interact with IH, which activated variably at
      potentials between -50 and -90 mV in different neurons. 6. We found that IH
      produces subthreshold response. Consistent with this, subthreshold resonance was
      blocked by external Cs+ but not Ba2+ or TTX. Application of Ba2+ enlarged FRCs
      and resonance at potentials below -80 mV, indicating that IK,ir normally
      attenuates resonance. Application of TTX greatly diminished resonance at
      potentials more depolarized than -65 mV, indicating that INaP normally amplifies
      resonance at these potentials. 7. The ZAP current input may be viewed as a model
      of oscillatory currents that arise in neocortical neurons during synchronized
      activity in the brain. We propose that the frequency selectivity endowed on
      neurons by IH may contribute to their participation in synchronized firing. The
      voltage dependence of the frequency-selective coupling between oscillatory inputs
      and spikes may indicate a novel mechanism for controlling the extent of low
      frequency synchronized activity in the neocortex.

PMID- 8871192
TI  - Models of subthreshold membrane resonance in neocortical neurons.
AB  - 1. We obtained whole cell data from sensorimotor cortical neurons of in vitro
      slices (juvenile rats) and observed a low-frequency resonance (1-2 Hz) in their
      voltage responses. We constructed models of subthreshold membrane currents to
      determine whether a hyperpolarization-activated cation current (IH) is sufficient
      to account for this resonance. 2. Parameter values for a basic IH (BH) model were
      estimated from voltage-clamp experiments at room temperature. The BH model formed
      a component of a reduced membrane (RM) model. On numerical integration, the RM
      model exhibited voltage sags and rebounds to injected current pulses; maximal
      voltage responses to injected oscillatory currents occurred near 2 Hz. 3. We
      compared the experimentally measured frequency-response curves (FRCs) at room
      temperature with the theoretical FRCs derived from the RM model. The theoretical
      FRCs exhibited resonant humps with peaks between 1 and 2 Hz. At 36 degrees C, the
      theoretical FRCs peaked near 10 Hz. The characteristics of theoretical and
      observed FRCs were in close agreement, demonstrating that IH is sufficient to
      cause resonance. Thus we classified IH as a resonator current. 4. We developed a
      technique, the reactive current clamp (RCC), to inject a computer-calculated
      current corresponding to a membrane ionic current in response to the membrane
      potential of the neuron. This enabled us to study the interaction of an
      artificial ionic current with living neurons (electronic pharmacology or EP
      method). Using the RCC, a simplified version of the BH model was used to cancel
      an endogenous IH (electronic antagonism) and to introduce an artificial IH
      (electronic expression) when an endogenous IH was absent. Antagonism of IH
      eliminated sags and rebounds, whereas expression of IH endowed neurons with
      resonance and the frequency-selective firing that accompanies resonance in
      neurons with an endogenous IH. Previous investigations have relied on the
      specificity of pharmacological agents to block ionic channels, e.g., Cs+ to block
      IH. However, Cs+ additionally affects other currents. This represents the first
      time an in vitro modeling technique (RCC) has been used to antagonize a specific
      endogenous current, IH. 5. A simplified RM model yielded values of the resonant
      frequency and Q (an index of the sharpness of resonance), which rose almost
      linearly between -55 and -80 mV. Resonant frequencies could be much higher than
      fH = (2 pi tau H) - 1 where tau H is the activation time constant for IH. 6. In
      the FRCs, resonance appeared as a hump at intermediate frequencies because of low
      and high-frequency attenuations due to IH and membrane capacitance,
      respectively. Changing the parameters of IH altered the low-frequency attenuation
      and, hence, the resonance. Changes in the leak conductance affected both the low-
      and high-frequency attenuations. 7. We modeled an inwardly rectifying K+ current
      (IIR) and a persistent Na+ current (INaP) to study their effects on resonance.
      Neither current produced resonance in the absence of IH. We found that IIR
      attenuated, whereas INaP amplified resonance. Thus IIR and INaP are classified as
      attenuator and amplifier currents, respectively. 8. Resonators and attenuators
      differ in that they have longer and shorter time constants, respectively,
      compared with the membrane time constant. Therefore, an increase in the leak
      conductance decreases the membrane time constant, which can transform an
      attenuator into a resonator, altering the frequency response. This suggests a
      novel mechanism for modulating the frequency responses of neurons to inputs. 9.
      These investigations have provided a theoretical framework for detailed
      understanding of mechanisms that produce resonance in cortical neurons. Resonance
      is one aspect of the intrinsic rhythmicity of neurons. The rhythmicity due to IH
      resonance is latent until it is revealed by oscillatory inputs. (ABSTRACT
      TRUNCATED)

PMID- 8871194
TI  - Motor unit recruitment in a distributed model of extraocular muscle.
AB  - 1. Eye position commands frequently are treated as a lumped, single-valued
      variable that is related linearly to eye position. As a step toward investigating
      how system-level linearity might be achieved despite nonlinear components, a
      distributed model of motor units in the abducens nucleus and lateral rectus
      muscle was constructed. 2. Parameters in the model were estimated using data from
      three main sources: measurement of length-tension curves for eye muscle in
      people, electrophysiological recording of ocular motoneuron properties in
      monkeys, and investigations of oculomotor unit properties in cat. Units (n = 100)
      in the distributed model were assigned equal strengths and for a given fixation
      command, the force developed by each unit was calculated, and the sum of unit
      forces compared with the active force in the entire muscle as measured
      experimentally. 3. The properties of the active units then were adjusted to
      reduce the size of any resultant error in a manner related to gradient descent
      methods for neural-net training. Distributed models were "trained" in this
      fashion for a series of eye positions drawn at random from the oculomotor range
      until performance stabilized. The goal of the training procedure was to obtain a
      good match between the output of the model and the experimental data on muscle
      force as a function of eye position. 4. Plots of trained motor-unit strength
      against ocular motoneuron threshold revealed a U-shaped pattern with the
      strongest units being recruited at both extremes of the oculomotor range and the
      weakest units recruited in the middle. The pattern remained unaltered
      qualitatively over a range of assumptions about the distribution of ocular
      motoneuron parameters and the relation between motoneuron firing rate and unit
      force. 5. The right-hand limb of the U-shaped pattern is similar to that observed
      in spinal motoneurons, where stronger units tend to have higher recruitment
      thresholds. The left-hand limb may reflect the two specializations of eye muscle:
      the functional need for very precise control of eye position in the middle of the
      oculomotor range and the use of multiply innervated muscle fibers to provide
      ripple-free control of eye position at low firing frequencies.

PMID- 8871193
TI  - Representation of passive hindlimb postures in cat spinocerebellar activity.
AB  - 1. We report here about the modulation of dorsal spinocerebellar tract (DSCT)
      activity by limb posture. In principle, DSCT activity could represent limb
      position in one of several ways. According to a classical notion of DSCT
      function, DSCT activity might be expected to correlate with changes in individual
      joint angles. However, given the evidence for extensive polysynaptic convergence
      onto DSCT units, it is reasonable to propose that DSCT activity represents more
      global variables such as the orientation of limb segments or the length and
      orientation of the whole limb. 2. In six anesthetized cats we recorded the
      activity of 96 antidromically identified DSCT neurons while a robot arm passively
      positioned the left hindfoot in 20 positions distributed in the sagittal plane,
      holding each position for 8 s. For each position we measured the joint angles,
      limb segment angles, and the length and orientation of the limb axis (defined as
      the line connecting the hip joint to the hindpaw). We used regression statistics
      to quantify 1) possible relationships among geometric variables of the hindlimb
      and 2) relationships between DSCT firing rate and limb variables. 3. First, we
      found a statistically significant relationship among the joint angles that could
      be described by a covariance plane accounting for approximately 70 percent of the
      total variance. Thus the 3 degrees of freedom represented by the joint angles in
      the sagittal plane are effectively reduced to only 2 by the coupling between
      joints. This finding resembles that described for the behaving cat during stance.
      However, the correlation between the hip and ankle angles in the passively
      displaced hindlimb was just the opposite of that observed during active stance.
      Moreover, we observed that the length and the orientation of the limb axis is
      determined simply by a linear combination of the three joint angles. 4. Most of
      the DSCT neurons (82 of 96) were significantly modulated by changes in foot
      position (1-way analysis of variance, P < 0.001). For those cells, we explored
      systematically how their activity was related to limb geometric variables. We
      found mostly linear relationships between individual joint or limb segments
      angles and DSCT firing rates. However, although these relationships were
      statistically significant, the random variance was often quite high. Moreover,
      approximately 70% of the cells were modulated by more than one joint or limb
      segment angle, suggesting that a model incorporating global geometric variables
      might explain a larger fraction of the variance in the neural data. 5.
      Consequently we tested how well DSCT activity was modulated by the length and the
      orientation of the limb axis with the use of a linear regression model with
      length and orientation (or the equivalent linear combination of joint angles) as
      predictors. We found that this model explained a larger fraction of the
      variability in the firing pattern of nearly every modulated cell than did any of
      the single joint models tested. 6. We also attempted to account for the effect of
      the mechanical joint covariance on this result by accounting for correlated
      independent variables in the analysis. We used a regression model incorporating
      all three joint or limb segment angles and performed a backward elimination of
      insignificant or redundant variables. The result was that 67% of the neurons were
      independently modulated by at least two joint angles, indicating that the
      modulation did not necessarily reflect the biomechanical constraint of joint
      angle covariation, but rather a central convergence of sensory information from
      more than a single joint. 7. From these results we conclude that the firing rates
      of a majority of DSCT neurons encode the position of the hindfoot relative to the
      hip joint.(ABSTRACT TRUNCATED)

PMID- 8871195
TI  - Thermosensitivity of acutely axotomized sensory nerve fibers.
AB  - 1. Thermosensitivity of axotomized myelinated and unmyelinated fibers in the
      sural nerve was examined in anesthetized rats within 24 h after nerve ligation
      and transection. Activity in single fibers was recorded extracellularly from
      small filaments dissected from the nerve approximately 20-30 mm proximal to the
      lesioned site. Cold and warm stimuli were applied to the ligated and cut nerve
      end or 5-10 mm further proximal. 2. Among 871 unmyelinated fibers tested, 40 were
      excited by cooling of the cut and ligated nerve end (8-15 degrees C), 44 were
      excited by warming (35-65 degrees C), and 16 were both cold and warm sensitive.
      None of the 438 myelinated fibers investigated were activated by either cold or
      warm stimuli. 3. Cold- and warm-sensitive fibers responded in a graded fashion to
      thermal stimuli of variable temperatures. Between 11 and 30 degrees C, the
      responses of cold-sensitive fibers increased when the temperature was reduced.
      Responses of warm-sensitive fibers increased between 40 and 65 degrees C, when
      the temperature was increased. 4. Thermosensitive fibers displayed characteristic
      response profiles. Responses to cold stimuli were maximal at the beginning and
      decreased continuously to lower discharge frequencies as the stimuli were
      maintained. The stimulus-response curves to warm stimuli were bell-shaped and
      discharge frequencies were maximal after 5-15 s. 5. In some cold-sensitive fibers
      a spatial gradient of excitability emerged after axotomy. Maximal responses to
      isothermal stimuli were observed at the transection site, whereas the
      excitability declined when the thermal stimuli were applied 5 and 10 mm further
      proximal. 6. After axotomy, 190 unmyelinated fibers were exposed to cold and warm
      stimuli at two sites 5 and 10 mm proximal of the nerve stump, and 172 intact C
      fibers were stimulated at anatomically comparable sites along the nerve. No
      statistically significant difference was found between the prevalences of
      thermosensitivity of C fibers along their axons in these two groups (7 of 172 vs.
      11 of 190). 7. In conclusion, some unmyelinated fibers can be ectopically excited
      by thermal stimuli within 24 h after nerve cut and ligation. This ectopically
      evoked activity may contribute to the generation of paresthesias, painful
      sensations, and associated changes following peripheral nerve lesion.

PMID- 8871196
TI  - Sympathetic modulation of activity in rat dorsal root ganglion neurons changes
      over time following peripheral nerve injury.
AB  - 1. We recorded from centrally connected axons isolated from the proximal stump of
      the sciatic nerve in intact rats and in rats whose nerves had been transected 4
      days-6 mo previously. Afferent axons selected for study had spontaneous impulse
      activity that originated ectopically in dorsal root ganglia (DRGs) L4 and L5. The
      sympathetic supply of these DRGs was excited by repetitive electrical stimulation
      of ventral roots T13 and L1. We examined quantitatively changes in afferent
      ongoing firing evoked by sympathetic stimulation. Results are based on
      observations from 161 neurons in rats with sciatic nerve injury and from 58
      neurons in control rats with intact sciatic nerves. Of these 219 neurons, 204 had
      myelinated fibers (A neurons) and 15 had unmyelinated fibers (C neurons), on the
      basis of measurements of conduction velocity. 2. In rats with nerve injury the
      majority of the spontaneously active neurons tested (95 of 161) responded to
      sympathetic stimulation with a change in ongoing firing frequency: 41 neurons
      exhibited a significant increase in discharge frequency that was often followed
      by suppression (28 of 41), and 54 neurons responded with a decrease in ongoing
      activity (simple suppression). In control rats, in contrast, only 1 of the 58
      spontaneously active sensory neurons tested responded to sympathetic stimulation.
      3. In A neurons, the response pattern changed systematically with time after
      sciatic nerve injury. At 4-22 days after nerve lesion, excitation was much more
      common than suppression. At 60-93 days, excitation and suppression occurred about
      equally. At 110-171 days, suppression was by far the more common response. 4. Of
      the 14 C neurons, 2 were excited by sympathetic stimulation (at 4-22 days
      postoperative) and 10 were suppressed (2 at 4-22 days, 8 at > 60 days). The only
      spontaneously active C neuron found in control rats was not affected by
      sympathetic stimulation. 5. The magnitude of responses in the three postoperative
      intervals investigated was similar. This was so for both the excitatory and the
      simple suppressive responses. The average latency between onset of stimulation
      and excitatory responses in afferent A fibers (approximately 10 s) was
      significantly less than the latency to simple suppressive responses
      (approximately 20 s). 6. The mean spontaneous firing rate of A neurons decreased
      with time after nerve lesion. No change was observed in C neuron activity. The
      mean firing rate of A neurons was significantly higher than that of C neurons 4
      93 days after nerve lesion, but not later. In all three postoperative periods
      investigated, the mean rate of spontaneous activity was the same in A neurons
      that responded to sympathetic stimulation and A neurons that did not. 7. The
      results show that nerve injury triggers sympathetic-sensory coupling within rat
      DRGs. Excitatory coupling is preferentially present in the period shortly after
      nerve injury, and is subsequently replaced by suppressive coupling. This suggests
      that there is a gradual change in the underlying coupling mechanism.

PMID- 8871197
TI  - Swelling-activated amino acid efflux in the human neuroblastoma cell line CHP
      100.
AB  - 1. The effects of hypoosmotic stress on cell volume and amino acid efflux were
      evaluated in the human neuroblastoma cell line CHP-100 with the Coulter Counter
      Multisizer and radiolabeled amino acid efflux, respectively. 2. CHP-100 cells
      swelled by approximately 35 +/- 5% (means +/- SE) when the osmolarity of the
      solution was decreased from 290 to 190 mOsm/kg H2O. The rapid swelling was
      followed by a biphasic regulatory volume decrease (RVD). 3. In cells loaded with
      14C-taurine, hypoosmotic stress induced a 300 +/- 22% (n = 23, P < 0.05) increase
      in taurine efflux compared with controls. This efflux was inhibited by the
      chloride channel blockers 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB),
      4,4'-diisothio-cyanostilbene-2,2'-disulfonic acid (DIDS), niflumic acid and by
      the volume-activated anion channel blocker tamoxifen. In addition, the swelling
      activated taurine efflux was dependent upon extracellular calcium. 4. Similarly,
      in cells loaded with 14C-glycine, hypoosmotic stress significantly increased
      glycine efflux, which was also sensitive to NPPB. In contrast, efflux of 3H
      glutamate was not significantly altered after hypoosmotic stress. 5. With the use
      of patch clamp recording techniques, Cl- channels were activated in cell attached
      patches after exposure to hypoosmotic solutions. 6. In nystatin perforated
      patches, permeability of the hypoosmotically activated anion channel was observed
      to be SCN- > I- > Br- > Cl- >> Glutamate. 7. It is concluded that in CHP-100
      cells, anion channels are activated during hypoosmotic stress and these channels
      represent a pathway for efflux of amino acids.

PMID- 8871198
TI  - Cochlear nerve activity after intense sound exposure in neonatal chicks.
AB  - 1. Single-neuron behavior in the cochlear nerve of neonatal (3-day-old) chicks
      was examined after exposure to a 120-dB SPL pure tone (0.9 kHz) for 48 h. Exposed
      animals were tested after 0 days or 12 days of recovery. Nonexposed chicks, age
      matched to the exposed animals, formed two control groups. 2. Spectral response
      plots were obtained from each cell. These plots described the neuron discharge
      rates in response to 1,767 tone burst stimuli, each with a unique frequency
      intensity combination. The tone bursts were presented at frequencies between 0.1
      and 4.5 kHz and for intensities between 0 and 100 dB SPL. From these plots the
      characteristic frequency (CF), CF threshold, and sharpness of tuning (Q10 dB)
      were derived for each cell. Frequency response-area functions at selected
      stimulus levels and rate-intensity functions at the CF were also constructed from
      the spectral response plots. In addition, spontaneous activity was determined.
      Data were obtained from 903 cells. 3. Neuron activity in the control cells
      revealed no differences between CF thresholds, Q10 dB, or spontaneous activity in
      the two age groups. However, age differences at all frequencies were noted in the
      rate-intensity functions. 4. A frequency-dependent loss in CF threshold was
      observed in the 0-day recovered cells. The threshold shift (relative to age
      matched control cells) was 55-65 dB between 0.8 and 1.5 kHz, but only 10-15 dB
      between 0.1-0.4 kHz and 2.5-3.5 kHz. The exposed cells showed no loss in
      frequency selectivity (Q10 dB) at < 0.5 kHz, whereas above this frequency an
      increasing deterioration in tuning was noted. Spontaneous activity in the 0-day
      cells was suppressed across the entire range of CFs. The rate-intensity function
      of exposed cells had a steeper growth rate than that of control cells. 5. At 12
      days of recovery, CF threshold, Q10 dB, and spontaneous activity all recovered to
      the levels exhibited by age-matched control cells. However, the rate-intensity
      function for cells with CFs between 0.8 and 1.0 kHz showed abnormal growth and
      higher discharge rates at saturation than the control cells. Outside of this
      frequency range the rate-intensity functions of control and exposed cells were
      similar to each other. 6. Recovery of function in the sound-damaged chick ear is
      accompanied by almost complete repair of the basilar papilla. The tectorial
      membrane, however, retains a major defect and only the lower layer of this
      membrane regenerates. An important observation in this presentation was the
      abnormal rate-intensity functions (in the 12-day recovered cells) reported for
      frequencies served by that region of the sensory epithelium where the tectorial
      membrane defect was found. This observation may be related to sustained
      structural damage to the short hair cell region of the papilla and/or alterations
      in the efferent control of papilla function mediated by the short hair cells.

PMID- 8871199
TI  - Sensory feedback and central afferent interaction in the muscle receptor organ of
      the crab, Carcinus maenas.
AB  - 1. An interaction exists between two proprioceptive afferent neurons innervating
      the thoracic-coxal muscle receptor organ (TCMRO) of the crab, Carcinus maenas.
      Intracellular recordings were made from the extraganglionic regions of the
      afferents in order to characterize this interaction and its effects on sensory
      feedback. 2. A current-induced depolarization of the nonspiking T fiber of the
      TCMRO results in a depolarization of the P fiber, a small-diameter (7 microns)
      neuron innervating the same receptor. This interaction is graded in amplitude,
      and may result in a single action potential being superimposed on the graded
      response of the P fiber. A hyperpolarization of the T fiber has a smaller effect
      on the P fiber than a depolarization of similar amplitude. The interaction is
      rectified in a T- to P-fiber direction, and has a minimum central delay of
      approximately 3.6 ms. 3. The site of the interaction between the afferents is
      situated centrally, within the thoracic ganglion. Action potentials evoked in the
      P fiber by a T-fiber depolarization propagate actively and antidromically to the
      periphery. 4. Central modulation of the interaction occurs, because the amplitude
      of a T-fiber-induced depolarization is reduced in the P fiber during centrally
      generated spontaneous bursts of activity in the motoneurons of basal leg muscles.
      5. Because of the interaction between T and P fibers, action potentials recorded
      from the peripheral portion of the P fiber during receptor stretch may be either
      orthodromic, resulting directly from the effects of the stretch on the sensory
      endings of the P fiber, or antidromic, resulting from the central input from the
      T fiber. 6. The T- to P-fiber interaction may serve to extend the dynamic
      sensitivity range of the P fiber, in particular by amplifying its sensory
      response at short receptor lengths and low velocities of stretch.

PMID- 8871200
TI  - Presynaptic inhibition of glutamatergic synaptic transmission to rat motoneurons
      by serotonin.
AB  - 1. In a brain stem slice preparation, we recorded glutamatergic excitatory
      postsynaptic currents (EPSCs) in hypoglossal motoneurons (HMs) evoked by
      extracellular stimulation in the reticular formation just ipsilateral to the
      hypoglossal motor nucleus (n. XII). Serotonin (5-HT) inhibited glutamatergic
      synaptic transmission in a dose-dependent fashion as indicated by a reduction in
      the evoked EPSC (eEPSC) peak amplitude to 46 +/- 2% (mean +/- SE, n = 26) of
      control (5-HT 10 microM). This effect was not voltage dependent, as the eEPSC
      reversal potential was not altered (n = 5). Additionally, 5-HT decreased the rate
      of rise of the eEPSC to 41 +/- 2% of control (n = 14). Blockade of N-methyl-D
      aspartate-receptor-channels by D(-)-2-amino-5-phosphonopentanoic acid (50 microM)
      or of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor
      channels by 6,7-dinitro-quinoxaline (20 microM) did not alter the relative
      reduction of the eEPSC amplitude by 5-HT (n = 7 and 3, respectively). 2. In the
      presence of tetrodotoxin (1 microM), bath application of 5-HT did not reduce
      postsynaptic glutamate currents elicited by pressure ejection of L-glutamate (1
      mM) onto HMs (n = 5), and it increased the median interevent interval of
      spontaneous miniature EPSCs (mEPSCs) to 178 +/- 12% of control (n = 4),
      suggesting that 5-HT acts presynaptically to reduce the probability of vesicle
      release. mEPSC amplitude was decreased slightly in three of four cells (median
      amplitude = 92 +/- 3% of control). 3. The specific 5-HT1B receptor agonist [3
      (1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one] (1 microM) mimicked 5-HT
      in its effect on eEPSCs (eEPSC amplitude reduced to 31 +/- 5% of control; rate of
      rise reduced to 40 +/- 4% of control, n = 10 and 5, respectively) and mEPSCs
      (median interevent interval increased to 231 +/- 36% of control; median mEPSC
      amplitude = 102 +/- 3% of control, n = 5). Additionally, 5-HT-mediated inhibition
      was not blocked by coapplication of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)
      butyl] piperazine hydrobromide (1 microM), a 5-HT1A antagonist, and 3-[2-[4-(4
      flurobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)-quin azolinedione tartrate (1
      microM), a 5-HT2A/2C antagonist (n = 4). These data indicate that the 5-HT effect
      is primarily 5-HT1B receptor mediated. 4. We conclude that 5-HT, acting through
      presynaptic 5-HT1B receptors, inhibits glutamatergic synaptic transmission by
      reducing the probability of vesicle release.

PMID- 8871201
TI  - Metabotropic glutamate receptors potentiate responses to NMDA and AMPA from layer
      V cells in rat visual cortex.
AB  - 1. With the use of whole cell recordings of layer V cells from slices of rat
      visual cortex, we demonstrate a potentiation of the response to N-methyl-D
      aspartate (NMDA) by the metabotropic glutamate agonist (1S,3R)-1-Amino-1,3
      cyclopentanedicarboxylic acid. This potentiation occurs within a few seconds and
      lasts a few minutes. 2. The potentiation is seen with tetrodotoxin in the
      perfusion solution, but is abolished by guanosine 5'-O-(2-thiodiphosphate) in the
      pipette solution, showing that it is a postsynaptic phenomenon. The potentiation
      is also abolished by alpha-methyl-4-carboxyphenylglycine in the bath solution,
      confirming that it is due to metabotropic glutamate receptors. 3. In 29 of 31
      cases tested, the response to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid was also potentiated, and the potentiation remained in the presence of the
      NMDA antagonist D-2-amino-5-phosphonovalerate.

PMID- 8871202
TI  - Inhibition of transient potassium current in cultured and acutely dissociated
      mouse hippocampal neurons by GABAA receptor activation.
AB  - 1. The regulation of A-current, one of several transient voltage-gated potassium
      currents, was studied using whole cell gigaohm seal voltage-clamp techniques on
      hippocampal pyramidal neurons that were either acutely dissociated from postnatal
      mouse brain or isolated from embryonic mouse brain and grown in dissociated
      culture. These neurons also express gamma-aminobutyric acid-A (GABAA) receptors,
      the activation of which can, under some circumstances, depolarize immature
      neurons and the dendrites of more mature neurons. 2. Application of GABA (50
      microM) reduced the amplitude of A-current when potassium current amplitude was
      measured during a period of slow and incomplete desensitization of IGABA. A
      current was reduced to 67 +/- 9% of control (mean +/- SD, n - 14) in acutely
      dissociated neurons, and to 64 +/- 11% of control (n = 15) in cultured neurons.
      Similar A-current reductions were seen in large outside-out membrane patches
      pulled from somata of cultured neurons, an observation suggesting that imperfect
      control of membrane voltage was not responsible for A-current inhibition. 3. A
      current inhibition exhibited the sensitivity expected of a GABAA-sensitive
      process. It was mimicked by muscimol and blocked by bicuculline, picrotoxin, and
      reduction of [Cl-] in the external solution. Baclophen and phaclophen, effective
      as agonist and antagonist on GABAB receptors, did not affect A-currents or their
      inhibition. Reduction in extracellular osmolarity (to increase cell swelling as
      might occur with Cl- entry), or removal of external HCO3- (which might flow
      inward through GABAA channels and cause local external acidification), did not
      affect A-current or its inhibition. The mechanisms of inhibition is not clear at
      present. 4. We suggest that reduced A-current may favor GABA-induced
      depolarization and consequent activation of voltage-gated calcium channels.

PMID- 8871203
TI  - Neurons in the supplementary eye field of rhesus monkeys code visual targets and
      saccadic eye movements in an oculocentric coordinate system.
AB  - 1. We investigated whether neurons in the supplementary eye field (SEF) of
      macaque monkeys code saccadic eye movements in oculocentric coordinates (relative
      to the current direction of fixation) or in craniocentric coordinates (relative
      to the head). Craniocentric coding in SEF had been previously suggested by the
      convergent appearance of electrically elicited saccades originating at different
      orbital positions. 2. We primarily studied SEF neurons that started responding
      before the beginning of saccades because such presaccadic activity is likely
      related to saccade generation and metrics. Using a memory-saccade task, we
      classified the presaccadic activity of each neuron as either purely visual
      related, purely movement related, or both visual and movement related. 3. We then
      mapped the response fields (receptive fields and movement fields) of SEF neurons
      from different orbital positions. When mapped relative to a central fixation
      point, the strongest responses for a given SEF neuron invariably occurred for a
      particular polar direction with fairly symmetrical declines for departures from
      that direction. When tested using other fixation point locations, their strongest
      responses almost always continued to occur for stimuli having the same polar
      direction relative to each fixation point tested, and thus they appeared to code
      both stimulus direction and saccade direction in an oculocentric coordinate
      system. 4. The effect of eye position on SEF presaccadic activity was quantified
      in two ways by computing, for each neuron, 1) an "intersection distance," the
      eccentricity of the point where extensions of the neuron's optimal polar
      directions measured at two eccentric orbital positions converged, and 2) an
      "orbital perturbation index" such that an index of 0 corresponded to no change in
      the neuron's optimal polar direction across different orbital positions (i.e.,
      perfectly oculocentric response fields) and an index of 1 corresponded to optimal
      polar directions that converged to the same craniocentric goal regardless of
      initial eye position (i.e., perfectly craniocentric response fields). For neurons
      with both visual and movement responses, these measures were calculated
      separately for each type of activity using tasks that temporally separated the
      visual cue presentation and the saccade to it. 5. Almost all of the intersection
      distances were well beyond the oculomotor range (+/- 50 degrees) of the monkey
      (38/39 for movement activity and 62/66 for visual activity). The median
      intersection distance for visual activity was very large (274 degrees), and the
      median for movement activity was slightly divergent (beyond infinity). Thus SEF
      neurons rarely showed a conspicuous convergence of response field direction. 6.
      Likewise, the mean orbital perturbation indexes were very small (-0.04 +/- 0.21,
      mean +/- SD, for movement activity and 0.09 +/- 0.15 for visual activity), also
      indicating that SEF neurons code stimuli and saccades in an oculocentric manner.
      7. For neurons with both visual and movement activities, the orbital perturbation
      indexes of the two activities were not significantly correlated (r = 0.16), even
      though their characteristic directions (optimal polar direction estimated from
      the center of the screen) were almost the same (circular correlation, r+ = 0.97).
      The lack of a significant correlation between the visual and movement activity
      orbital perturbation indexes is consistent with the hypothesis that most of the
      variation in this index represents statistically independent errors of
      measurement. Conversely, the strong covariation of visual and movement activity
      characteristic directions indicates that directional preference is a fundamental
      functional property of SEF presaccadic activity.(ABSTRACT TRUNCATED)

PMID- 8871204
TI  - Effects of bilateral lesions of the dorsolateral funiculi and dorsal columns at
      the level of the low thoracic spinal cord on the control of locomotion in the
      adult cat. I. Treadmill walking.
AB  - 1. A quantitative and longitudinal analysis of locomotion was made after
      bilateral lesions of the dorsolateral funiculi (DLF) and/or the dorsal columns
      (DC) in the lower thoracic cord (T12 or T13) in five adult cats. All cats were
      chronically implanted several weeks before the spinal cord lesion to permit the
      recording of electromyographic (EMG) activity from selected flexor and extensor
      muscles of the fore- and hindlimbs of each side. This allowed each cat to act as
      its own control when comparing the pattern and amplitude of EMG activity before
      and after the lesion. All experiments were also videotaped to allow an analysis
      of the kinematic changes before and after the lesions. Kinematic data were only
      analyzed for the side of the cat facing the camera; for all cats this was the
      left side. 2. After recovery periods of 2-5 mo, wheat-germ-agglutinated
      horseradish peroxidase (WGA-HRP) was injected caudal to the lesion site (normally
      at L2). The extent of the lesion was verified both histologically and by
      evaluating the number of HRP-labeled neurons in different supraspinal structures.
      These analyses showed that the cortico- and rubrospinal tracts (CST and RST,
      respectively) were completely interrupted, bilaterally, in two of five of the
      cats; in one of these cats the DCs were also interrupted. In the other three cats
      there was more variable damage, and the CST and RST were only completely
      interrupted on the right side of one of these animals. The DCs were completely
      sectioned in two of these cats. 3. During the 1st wk subsequent to the lesion,
      most cats had difficulty in supporting their weight and in walking. However,
      within 10 days all were able to walk, unaided, for extended periods on the
      treadmill at speeds of at least 0.35 m/s. In the two cats with the complete,
      bilateral DLF lesions, the animals dragged both their left and right hindpaws
      along the treadmill belt during the swing phase of the step cycle (paw drag)
      throughout the testing period of 3-5 mo. In the other three cats, paw drag in
      either hindlimb was only seen in the 1st 2-3 wk after the lesions, with the
      exception of the cat with the complete lesion of the DLF on the right side, which
      showed sustained paw drag in the right hindlimb throughout the testing period. 4.
      Significant increases in step cycle and swing duration following the lesion were
      observed only in the two cats with the largest lesions. In all five cats,
      statistical comparisons of the slopes from a linear regression analysis showed
      that the relationship between swing and step cycle duration was unchanged by the
      lesions. 5. Joint angles in the left hindlimb of the two cats with the largest
      lesions were generally smaller (more flexed) than in the prelesion controls. This
      was particularly true for the knee and ankle joints. The other three cats showed
      changed joint angle values for the hip, knee, and ankle only in the 1st 2-3 wk
      after the lesions. All of the cats, except the one with the least damage to the
      left DLF, exhibited increased joint excursions at the metatarsophalangeal (MTP)
      joint of the left limb throughout the recovery period. 6. There were sustained
      changes in the coupling between the hip and the knee of the left limb, together
      with smaller changes in the coupling of the knee and ankle in the two cats with
      the complete lesions of the DLF. In contrast to the prelesion controls, flexion
      at the ankle occurred before swing onset in these same two cats. The changes in
      the coordination between the hip and the knee were associated with changes in the
      temporal coupling between the hip flexor, sartorius (Srt), and the knee flexor,
      semitendinosus (St). Despite some improvement, the coupling between these two
      muscles never fully recovered to the prelesion values. Similar, but smaller,
      changes in the delay between Srt and St were also seen in two of the other three
      cats. (ABSTRACT TRUNCATED)

PMID- 8871205
TI  - Mechanisms of oscillation in dynamic clamp constructed two-cell half-center
      circuits.
AB  - 1. The dynamic clamp was used to create reciprocally inhibitory two-cell circuits
      from pairs of pharmacologically isolated gastric mill neurons of the
      stomatogastric ganglion of the crab, Cancer borealis. 2. We used this system to
      study how systematic alterations in intrinsic and synaptic parameters affected
      the network behavior. This has previously only been possible in purely
      computational systems. 3. In the absence of additional hyperpolarization
      activated inward current (IH), stable half-center oscillatory behavior was not
      observed. In the presence of additional IH, a variety of circuit dynamics,
      including stable half-center oscillatory activity, was produced. 4. Stable half
      center behavior requires that the synaptic threshold lie within the voltage
      envelope of the slow wave oscillation. 5. Changes in the synaptic threshold
      produce dramatic changes in half-center period. As predicted by previous
      theoretical work, when the synaptic threshold is depolarized, the period first
      increases and then decreases in a characteristic inverted U-shaped relationship.
      Analysis of the currents responsible for the transition between the active and
      inhibited neurons shows that the mechanism of oscillation changes as the synaptic
      threshold is varied. 6. Increasing the time constant and the conductance of the
      inhibitory synaptic current increased the period of the half-center oscillator.
      7. Increasing the conductance of IH or changing the voltage dependence of IH can
      either increase or decrease network period, depending on the initial mode of
      network oscillation. A depolarization of the activation curve causes the network
      to respond in a similar fashion as increasing the conductance of IH. 8. Many
      neuromodulatory substances are known to alter synaptic strength and the
      conductance and voltage dependence of IH, parameters we studied with the dynamic
      clamp. To understand the response of the network to modulation of a single
      parameter, it is necessary to understand the nature of the altered conductance
      and how it interacts with the other conductances in the system.

PMID- 8871206
TI  - Variability and interhemispheric asymmetry of single-whisker functional
      representations in rat barrel cortex.
AB  - 1. The rat whisker-to-barrel system was used to investigate the variability and
      interhemispheric asymmetry in the functional organization of primary
      somatosensory cortex as assessed with intrinsic signal optical imaging. The areal
      extent of whisker D1 functional representation was determined for both the left
      and right barrel cortex of each of 10 adult male rats. The average size of
      whisker D1 functional representation and the amount of variability away from this
      average across animals were determined. In addition, interhemispheric asymmetry
      was addressed at both the population level and the individual level. The degree
      of side preference for thigmotactic scanning (typical whisker-related rodent
      behavior) was determined for each rat in an attempt to find a behavioral
      correlate for the degree of interhemispheric asymmetry in the size of whisker D1
      functional representation. 2. The average areal extent of whisker D1 functional
      representation (defined as area at half-height) was large (1.95 +/- 0.14 mm2,
      mean +/- SE, N = 10 rats), suggesting that stimulation of a single whisker evokes
      activity over a large cortical area that includes other whisker representations.
      3. The average size of whisker D1 functional representation was not significantly
      different between the left (1.86 +/- 0.21 mm2) and right (2.04 +/- 0.15 mm2)
      hemispheric side, suggesting that interhemispheric functional asymmetry of barrel
      cortex is not systematic toward a specific hemispheric side at the population
      level. 4. The degree of variability in the size of whisker D1 functional
      representation from the left hemisphere ranged between 54.6% smaller than to
      50.6% larger than the left average areal extent. A large degree of variability
      was also observed for the right D1 representation, 37.6% smaller than to 34.9%
      larger than the right average areal extent. Thus it appears that a large
      variability in the size of unmanipulated single-whisker functional
      representations exists across animals from the same species and is not exclusive
      to a particular hemispheric side. 5. In 5 of 10 rats, the size of whisker D1
      functional representation between the two hemispheres differed by > or = 25%
      within an individual animal. Of these five rats, four had a larger representation
      in their right hemisphere. The degree and direction of behavioral asymmetry was
      not linearly correlated with the interhemispheric asymmetry in the size of D1
      functional representation (r = 0.494). 6. The large size of a single-whisker
      functional representation as defined with intrinsic signal optical imaging is
      discussed with respect to previous anatomic and 2-deoxyglucose autoradiography
      studies, whereas the large variability in this size across animals is discussed
      with respect to the individuality of each animal. In addition, the results of the
      present study have implications for projects that plan to investigate relative
      changes in the size of single-whisker functional representations.

PMID- 8871207
TI  - Visual motion processing in the anterior ectosylvian sulcus of the cat.
AB  - 1. Neurons that are selectively sensitive to the direction of motion of elongated
      contours have been found in several cortical areas in many species. However, in
      the striate cortex of the cat and monkey, and the extrastriate posteromedial
      lateral suprasylvian visual area of the cat, such cells are generally component
      motion selective, signaling only the direction of movement orthogonal to the
      preferred orientation; a direction that is not necessarily the same as the motion
      of the entire pattern or texture of which the cell's preferred contour is part.
      The primate extrastriate middle temporal area is the only cortical region
      currently known to contain a substantial population of pattern-motion-selective
      cells that respond to the shared vector of motion of mixtures of contours. 2.
      From analyzing published data on the connectivity of the cat's cortex, we
      predicted that the anterior ectosylvian visual area (AEV), situated within the
      anterior ectosylvian sulcus, might be a higher-order motion processing area and
      thus likely to contain pattern-motion-selective neurons. This paper presents the
      results of a study on neuronal responses in AEV. 3. Ninety percent of AEV cells
      that responded strongly to drifting grating and/or plaid stimuli were
      directionally selective (directionality index > 0.5). For this group, the mean
      directionality index was 0.75. Moreover, 55% of these cells were unequivocally
      classified as pattern motion selective and only one neuron was classified as
      definitely component motion selective. Thus high-level pattern motion coding
      occurs in the cat extrastriate cortex and is not limited to the primate middle
      temporal area. 4. AEV contains a heterogeneous population of directionally
      selective cells. There was no clear relation between the degree of directional
      selectivity for plaids or gratings and the degree of selectivity for pattern
      motion or component motion. Nevertheless, 28% of the highly responsive cells were
      both more strongly modulated by plaids than gratings and more pattern motion
      selective than component motion selective. Such cells could correspond to a
      population of "selection units" signaling the salience of local motion
      information. 5. AEV lacks global retinotopic order but the preferred direction of
      motion of neurons (rather than axis of motion, as in the middle temporal area and
      the posteromedial lateral suprasylvian visual area) is mapped systematically
      across the cortex. Our data are compatible with AEV being a nonretinotopic,
      feature-mapped area in which cells representing similar parts of "motion space"
      are brought together on the cortical sheet.

PMID- 8871208
TI  - Activity of visuomotor burst neurons in the superior colliculus accompanying
      express saccades.
AB  - 1. We recorded visuomotor burst neurons in the deeper layers of the superior
      colliculus while two monkeys (Macaca fascicularis) made short-latency saccades
      known as express saccades to visual targets in order to determine whether the
      visual discharge normally seen for these cells served as the premotor burst
      during express saccades. We then compared saccade-related activity during express
      saccades with that recorded during regular latency saccades and delayed saccades.
      2. Saccade latency histograms for two monkeys during trials with a temporal gap
      between fixation-point offset and target onset showed a distinct peak of saccades
      around 70-80 ms. One monkey also showed an additional peak around 125 ms. 3.
      Express saccades were found on the average to have the same relationship of
      saccade peak velocity to saccade amplitude as regular latency saccades and
      delayed saccades. Express saccades tended to be somewhat more hypometric than the
      other classes of saccades. However, express saccades were clearly visually guided
      and not anticipatory responses. 4. For most cells studied (33/40), express
      saccades were accompanied by a single, uninterrupted burst of activity beginning
      40-50 ms after target onset and continuing until sometime around the end of the
      saccade. For a smaller group of cells (7/40), two peaks of burst activity were
      seen, although the second peak was smaller and tended to occur late, after
      saccade onset. Across all cells, the peak of visuomotor cell activity during
      express saccades correlated just as well with target onset as it did with saccade
      onset. 5. When considered as discharge temporally aligned to the onset of the
      saccade, bursts accompanying express saccades tended to begin at approximately
      the same time as that for regular and delayed saccades. However, this discharge
      generally peaked earlier for express than for regular and delayed saccades. Also,
      the magnitude of discharge for express saccades was higher than that for delayed
      saccades throughout the burst. 6. When considered as discharge temporally aligned
      to the appearance of the target, bursts began earlier for express and regular
      saccade trials than for delayed saccade trials. Peak discharge tended to be
      greater for express saccades than for the other classes of saccades. 7. The
      results of this investigation are consistent with the suggestion that the visual
      burst of visuomotor neurons in the deeper layers of the superior colliculus plays
      a role in the initiation of express saccades similar to that played by the
      premotor burst for saccades of longer latency. The elevated discharge for express
      saccades supports the idea that the superior colliculus plays a more critical
      role in express saccade generation than in the generation of longer-latency
      saccades. The elevated discharge also suggests that visuomotor bursters do not
      code one-to-one for saccade velocity nor for saccade dynamic motor error.

PMID- 8871209
TI  - Combined eye-head gaze shifts produced by electrical stimulation of the superior
      colliculus in rhesus monkeys.
AB  - 1. We electrically stimulated the intermediate and deep layers of the superior
      colliculus (SC) in two rhesus macaques free to move their heads both vertically
      and horizontally (head unrestrained). Stimulation of the primate SC can elicit
      high-velocity, combined, eye-head gaze shifts that are similar to visually guided
      gaze shifts of comparable amplitude and direction. The amplitude of gaze shifts
      produced by collicular stimulation depends on the site of stimulation and on the
      parameters of stimulation (frequency, current, and duration of the stimulation
      train). 2. The maximal amplitude gaze shifts, produced by electrical stimulation
      at 56 sites in the SC of two rhesus monkeys, ranged in amplitude from
      approximately 7 to approximately 80 deg. Because the head was unrestrained,
      stimulation-induced gaze shifts often included movements of the head. Head
      movements produced at the 56 stimulation sites ranged in amplitude from 0 to
      approximately 70 deg. 3. The relationships between peak velocity and amplitude
      and between duration and amplitude of stimulation-induced head movements and gaze
      shifts were comparable with the relationships observed during visually guided
      gaze shifts. The relative contributions of the eyes and head to visually guided
      and stimulation-induced gaze shifts were also similar. 4. As was true for
      visually guided gaze shifts, the head contribution to stimulation-induced gaze
      shifts depended on the position of the eyes relative to the head at the onset of
      stimulation. When the eyes were deviated in the direction of the ensuing gaze
      shift, the head contribution increased and the latency to head movement onset was
      decreased. 5. We systematically altered the duration of stimulation trains (10
      400 ms) while stimulation frequency and current remained constant. Increases in
      stimulation duration systematically increased the amplitude of the evoked gaze
      shift until a site specific maximal amplitude was reached. Further increases in
      stimulation duration did not increase gaze amplitude. There was a high
      correlation between the end of the stimulation train and the end of the evoked
      gaze shift for movements smaller than the site-specific maximal amplitude. 6.
      Unlike the effects of stimulation duration on gaze amplitude, the amplitude and
      duration of evoked head movements did not saturate for the range of durations
      tested (10-400 ms), but continued to increase linearly with increases in
      stimulation duration. 7. The frequency of stimulation was systematically varied
      (range: 63-1,000 Hz) while other stimulation parameters remained constant. The
      velocity of evoked gaze shifts was related to the frequency of stimulation;
      higher stimulation frequencies resulted in higher peak velocities. The maximal,
      site-specific amplitude was independent of stimulation frequency. 8. When
      stimulating a single collicular site using identical stimulation parameters, the
      amplitude and direction of stimulation-induced gaze shifts, initiated from
      different initial positions, were relatively constant. In contrast, the amplitude
      and direction of the eye component of these fixed vector gaze shifts depended
      upon the initial position of the eyes in the orbits; the endpoints of the eye
      movements converged on an orbital region, or "goal," that depended on the site of
      collicular stimulation. 9. When identical stimulation parameters were used and
      when the eyes were centered initially in the orbits, the gaze shifts produced by
      caudal collicular stimulation when the head was restrained were typically smaller
      than those evoked from the same site when the head was unrestrained. This
      attenuation occurred because stimulation drove the eyes to approximately the same
      orbital position when the head was restrained or unrestrained. Thus movements
      produced when the head was restrained were reduced in amplitude by approximately
      the amount that the head would have contributed if free to move. 10. When the
      head was restrained, only the eye component of the intended gaze shift

PMID- 8871210
TI  - Facilitation of long-term potentiation by prior activation of metabotropic
      glutamate receptors.
AB  - 1. The influence of prior metabotropic glutamate receptor (mGluR) activation on
      subsequent long-term potentiation (LTP) induction was investigated with the use
      of the mGluR agonist 1-amino-cyclopentane-1S,3R-dicarboxylic acid (ACPD, 20
      microM). Field potential recordings were made in the stratum radiatum of CA1
      slices taken from young adult male rats and from which CA3 was routinely
      dissected. Theta burst stimulation (TBS) just above threshold was used to induce
      LTP. 2. A 10-min bath application of ACPD begun 30 min before the TBS facilitated
      the induction of LTP in a dose-dependent manner and resulted in an enhanced
      magnitude and stability of LTP. 3. ACPD did not enhance the degree of LTP induced
      by strong TBS, suggesting that it acts to lower the threshold for LTP induction
      but does not raise the ceiling on the amount of inducible LTP. 4. This priming
      effect by ACPD was stereo specific and lasted between 1 and 3 h. Synaptic
      stimulation during the ACPD application was not necessary for the enhancement of
      LTP. Blockade of N-methyl-D-aspartate receptors (NMDARs) during ACPD application
      also failed to affect the enhancement of LTP. 5. ACPD-induced priming of LTP was
      antagonized by L-2-amino-3-phosphonopropionic acid, suggesting an involvement of
      group I mGluRs. 6. ACPD-induced enhancement of LTP was not secondary to long
      lasting changes in NMDAR activation or GABAAergic inhibition, because it was
      unaffected by the addition of picrotoxin, a gamma-aminobutyric acid-A (GABAA)
      receptor antagonist, and isolated NMDAR-mediated responses did not show a long
      lasting enhancement in response to ACPD application. 7. These data demonstrate
      that activation of mGluRs can initiate persistent yet covert changes in synaptic
      function that facilitate the stable induction of LTP.

PMID- 8871211
TI  - Two distinct low-voltage-activated Ca2+ currents contribute to the pacemaker
      mechanism in cockroach dorsal unpaired median neurons.
AB  - 1. The contribution of Ca2+ currents to the endogenous firing properties of
      cockroach isolated adult dorsal unpaired median neurons was investigated using
      whole cell patch-clamp technique with 5 mM Ca2+ as the charge carrier. At least
      three types of Ca2+ currents, a high-voltage-activated Ca2+ current and two low
      voltage-activated (LVA) Ca2+ currents, have been found in these neurons. This
      study focused on the LVA Ca2+ currents, which are suitable candidates in the
      generation of the slow predepolarization because of their low threshold of
      activation. 2. The global LVA Ca2+ current could be dissociated by means of
      nickel sensitivity, deactivation time constant and voltage dependence of time to
      peak, tail current amplitude and inactivation, as transient and maintained LVA
      Ca2+ currents. 3. The transient LVA Ca2+ current, sensitive to 100 microM Ni2+,
      was isolated by using a subtraction procedure. It was activated at -70 mV and
      half-inactivated at -59.5 mV. The inactivation was purely voltage dependent.
      Current-clamp experiments performed with 150 microM Ni2+ indicated that this
      current was involved in the initial part of the predepolarization. 4. The
      maintained LVA Ca2+ current, resistant to 100 microM Ni2+, was activated in a
      range of potential 10 mV more positive than the transient LVA Ca2+ current, and
      its voltage dependence of inactivation displayed a U-shaped-curve. 5. Replacing
      Ca2+ with Ba2+ in equimolar amount or low internal Ca2+ concentration [5 mM bis
      (o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) in the pipette] induced a
      monotonic voltage dependence of inactivation and increased the rate of relaxation
      of this current. These effects were mimicked by high internal Ca2+ concentration
      [0.1 mM Ca2+ and no ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid in the pipette]. This demonstrated an unusual Ca2+-sensitive
      inactivation process that varied over a narrow range of Ca2+ concentrations. 6.
      Current-clamp experiments performed under 150 microM Ni2+, with 15 mM external
      Ca2+ concentration (which potentiated the maintained LVA current within 30 s of
      superfusion) or with 5 mM BAPTA in the pipette demonstrated the participation of
      this current in the last two-thirds of the slow predepolarizing phase. 7. Our
      findings demonstrated, for the first time in neurosecretory cells, the
      coexistence of two distinct LVA Ca2+ currents, which have specialized function in
      the generation of the pacemaker activity.

PMID- 8871212
TI  - Pharmacological dissection of high-voltage-activated Ca2+ current types in
      acutely dissociated rat supraoptic magnocellular neurons.
AB  - 1. We used pharmacological blockers and whole cell voltage-clamp recordings from
      acutely dissociated magnocellular neurons from the rat supraoptic nucleus to test
      for the presence of L-, N-, P-, Q-, and R-type calcium currents. 2. We found
      clear evidence for L-type (dihydropyridine sensitive), N-type (blocked by omega
      conotoxin (GVIA), and P-type (blocked by omega-agatoxin IVA) currents. Nifedipine
      blocked 28 +/- 2% (mean +/- SE) of the current, omega-conotoxin GVIA blocked 26
      +/- 4%, and omega-agatoxin IVA (25-30 nM) blocked 17 +/- 4%. In addition, omega
      conotoxin MVIIC blocked about half (54 +/- 2%) of the current remaining after L-,
      N-, and P-type currents were blocked, suggesting the presence of Q-type currents.
      3. About 20% of the whole cell current was unblocked by the combination of all
      four blockers, suggesting the presence of a fifth current type. This residual
      current inactivated slowly at -10 mV.

PMID- 8871213
TI  - Calcium-induced long-term depression in the visual cortex of the rat in vitro.
AB  - 1. In many brain areas, including neocortex and hippocampus, excitatory synapses
      can undergo both long-term potentiation (LTP) and long-term depression (LTD). It
      is established that a change in the postsynaptic calcium concentration ([Ca2+]i)
      is critical for the induction of both LTP and LTD. Protocols that induce these
      long-term synaptic modifications typically involve afferent stimulation. But, in
      hippocampus, LTP can also be induced by a transient increase of the extracellular
      calcium concentration ([Ca2+]o). The purpose of the present study was to
      determine whether raising [Ca2+]o also induces long-term modifications of
      excitatory synaptic transmission in the neocortex. 2. Intracellular recordings
      were obtained from regular spiking cells in layers II-III of slices of the rat
      visual cortex. Test stimuli were evoked with stimulation electrodes located in
      the white matter (w.m.) below the recorded cell and intracortically (i.c.)
      adjacent to the cell. Both the depolarizing slope and the amplitude of excitatory
      postsynaptic potentials (EPSPs) were measured. For exposure to elevated [Ca2+]o,
      the normal medium ([Ca2+]o = 2 mM) was exchanged for a period of 10 min against a
      medium containing 4 mM [Ca2+]o. 3. Elevated [Ca2+]o leads, after return to normal
      medium, to a long-lasting decrease of intracellularly recorded synaptic responses
      to both w.m. and i.c. stimulation even if activation of these two pathways is
      discontinued or N-methyl-D-aspartate (NMDA) receptors are blocked during elevated
      [Ca2+]o. This decrease is due to reduced efficacy of excitatory transmission
      because it is observed in the presence of the gamma-aminobutyric acid-A (GABAA)
      receptor antagonist, bicuculline. 4. Induction of LTD by raising [Ca2+]o is
      voltage dependent. First, elevated [Ca2+]o elicits LTD only in cells whose
      resting membrane potential (Vmr) is less polarized than -79 mV (and more
      polarized than -70 mV, which is the Vmr of the least polarized cell). Second,
      hyperpolarizing cells whose Vmr is in this susceptible range by 20 mV below Vmr
      during exposure to high [Ca2+]o prevents Ca2+-induced LTD. Third, when elevated
      [Ca2+]o is associated with postsynaptic depolarizing pulses, LTD is readily
      induced in cells whose Vmr is more polarized than -79 mV. This voltage dependence
      implies that the depression is induced by a postsynaptic process and hence that
      it occurs at synapses formed by excitatory terminals on the recorded neuron. 5.
      Assuming that a transient elevation of [Ca2+]o leads to an increase of [Ca2+]i,
      the results of this study suggest that a transient increase of [Ca2+]i is
      sufficient to elicit LTD. This may provide a mechanism for the induction of
      heterosynaptic LTD, a depression that occurs in afferents that are silent while
      the postsynaptic neuron is activated by other inputs.

PMID- 8871214
TI  - A delayed rectifier conductance in type I hair cells of the mouse utricle.
AB  - 1. Membrane currents of hair cells in acutely excised or cultured mouse utricles
      were recorded with the whole cell voltage-clamp method at temperatures between 23
      and 36 degrees C. 2. Type I and II hair cells both had delayed rectifier
      conductances that activated positive to -55 mV. 3. Type I, but not type II, hair
      cells had an additional delayed rectifier conductance (gK,L) with an activation
      range that was unusually negative and variable. At 23-25 degrees C, V(1/2) values
      ranged from -88 to -62 mV in 57 cells. 4. gK,L was very large. At 23-25 degrees
      C, the average maximum chord conductance was 75 +/- 65 nS (mean +/- SD, n = 57;
      measured at -54 mV), or approximately 21 nS/pF of cell capacitance. 5. gK,L was
      highly selective for K+ over Na+ (permeability ratio PNa+/PK+:0.006), but unlike
      other delayed rectifiers, gK,L was significantly permeable to Cs+
      (PCs+/PK+:0.31). gK,L was independent of extracellular Ca2+. 6. At -64 mV, Ba2+
      and 4-aminopyridine blocked gK,L with apparent dissociation constants of 2.0 mM
      and 43 microM, respectively. Extracellular Cs+ (5 mM) blocked gK,L by 50% at -124
      mV. Apamin (100 nM) and dendrotoxin (10 nM) has no effect. 7. The kinetic data of
      gK,L are consistent with a sequential gating model with at least two closed
      states and one open state. The slow activation kinetics (principal time constants
      at 23-25 degrees C:600-200 ms) had a thermal Q10 of 2.1. Inactivation (Q10:2.7)
      was partial at all temperatures. Deactivation followed a double-exponential time
      course and had a Q10 of 2.0. 8. At 23-25 degrees C, gK,L was appreciably
      activated at the mean resting potential of type I hair cells (-77 +/- 3.1 mV, n =
      62), so that input conductances were often more than an order of magnitude larger
      than those of type II cells. If these conditions hold in vivo, type I cells would
      produce unusually small receptor potentials. Warming the cells to 36 degrees C
      produced parallel shifts in gK,L's activation range (0.8 +/- 0.3 mV/degrees C, n
      = 8), and in the resting potential (0.6 +/- 0.3 mV/degrees C, n = 4). Thus the
      high input conductances were not an artifact of unphysiological temperatures but
      remained high near body temperature. It remains possible that in vivo gK,L's
      activation range is less negative and input conductances are lower; the large
      variance in the voltage range of activation suggests that it may be subject to
      modulation.

PMID- 8871215
TI  - Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is
      reduced during central sensitization.
AB  - 1. In our previous work, we demonstrated that the glycinergic and GABAergic
      mechanisms that help mediate the descending inhibition from the periaqueductal
      gray exert a tonic modulation of nociceptive inputs through spinal glycine and
      gamma-aminobutyric acid (GABA) receptors. This study was designed to examine
      further possible changes in the inhibition of the activity of spinothalamic tract
      (STT) neurons mediated by spinal glycine and GABA receptors when STT cells are
      sensitized by intradermal injection of capsaicin, and to investigate the role of
      the protein kinase C (PKC) system in the functional modulation of these
      receptors. 2. Although the responses of STT cells to cutaneous mechanical stimuli
      were sensitized by intradermal injection of capsaicin, the inhibition of the
      responses of all STT cells tested to noxious cutaneous stimuli produced by
      iontophoretic release of glycine and GABA was significantly attenuated. The
      inhibition elicited by iontophoretic application of a GABAA agonist, muscimol,
      was reduced in some of the cells tested. 3. When the spinal cord dorsal horn was
      pretreated with a selective PKC inhibitor, 2,6-diamino-N-([1-oxotridecyl-2
      piperidinyl]- methyl)hexanamide, by microdialysis, sensitization of STT cells by
      capsaicin injection and the accompanying attenuation of glycine- and GABA-induced
      inhibition were prevented. 4. Sensitization of STT cells to cutaneous mechanical
      stimuli was also induced by administration of the PKC activator, 12-O
      tetradecanoylphorbol-13-acetate, into the spinal dorsal horn. The inhibition
      produced by iontophoretic release of glycine, GABA, and muscimol was found to be
      reduced in most cells examined when this phorbol ester was used. An inactive
      phorbol ester, 4 alpha-phorbol 12,13-didecanoate, did not produce significant
      effects on cellular activity. 5. These results suggest that there is an
      activation of PKC in the spinal cord when STT neurons are sensitized after
      intradermal injection of capsaicin or administration of phorbol ester. This
      sensitization is likely to be involved in the development of allodynia and
      secondary hyperalgesia not only by enhancing the responses of excitatory amino
      acid receptors but also by desensitizing glycine and GABA receptors.

PMID- 8871216
TI  - Local mechanisms of phase-dependent postsynaptic modifications of NMDA-induced
      oscillations in the abducens motoneurons: a simulation study.
AB  - 1. In vivo experiments have shown that extracellular microelectrophoretic
      application of N-methyl-D-aspartate (NMDA) induced oscillatory plateau potentials
      with bursts of action potentials in rat abducens motoneurons. The period of these
      slow NMDA oscillations could be altered by single trigeminal non-NMDA excitatory
      input delivered at low frequency during the NMDA oscillations. 2. A resetting of
      the oscillations was observed depending on the phase of slow oscillatory cycle
      during which the trigeminal excitation occurred. 3. We investigated local
      mechanisms responsible for the phase-dependent modifications of NMDA
      oscillations, including contributions of voltage and concentration transients, in
      the mathematical model of the isopotential membrane compartment equipped with
      voltage-gated Na+, K+, and Ca2+ channels, with Ca2+-dependent K+ channels, and
      with ligand-gated NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptor channels. The faithful model was constructed with the use of
      models described earlier, which were modified by increasing time constants of
      kinetic variables of all voltage-gated conductances and by including coupled
      dynamics of voltages and ion concentrations. The changes in ion concentrations
      were produced near the membrane by transmembrane currents and removal mechanisms
      (pumps, diffusion). 4. This work focuses on local arrangement of voltage- and
      ligand-gated conductances and on local ion concentration changes in two separate
      pools: the postsynaptic pool of AMPA receptors and the extrasynaptic pool. In
      terms of the electrotonic and diffusional length constants, these pools were
      electrotonically close but diffusionally remote. 5. It was found that the effect
      of resetting can be produced by a local interaction between plateau and spike
      generating conductances and glutamate receptors. 6. In vivo phase-dependent
      interactions between NMDA oscillations and AMPA synaptic input were reproduced by
      the local model only when changes in intracellular sodium and extracellular
      potassium concentrations were taken into account and the mechanisms of ion
      removal from postsynaptic pools had slower kinetics than the fast pump system
      operating in the extracellular pool. 7. Postsynaptic changes in ion
      concentrations of Na+ and K+ in intra- and extracellular layers near the membrane
      shift of Nernst equilibrium potentials for these ions depending on the phase of
      activation of synaptic input. Thus Na+ and k+ components of all transmembrane
      currents involved in the pattern generation are differently affected by synaptic
      action during the oscillations. We conclude that slow postsynaptic changes in ion
      concentrations near the membrane play a key role in the resetting of the NMDA
      oscillations.

PMID- 8871217
TI  - Local effects of glycinergic inhibition in the spinal cord motor systems for
      swimming in amphibian embryos.
AB  - 1. We have studied the effects of locally applying the glycinergic antagonist
      strychnine to rhythmically active spinal neurons in amphibian embryos during
      fictive swimming. Intracellular recordings were made from motoneurons and
      premotor interneurons in Xenopus laevis, a well-studied model system, and from
      motoneurons in three other species (Rana temporaria, Bufo bufo, and Triturus
      vulgaris). Overall, these embryos cover a range of swimming patterns from the
      short-cycle-period, brief-motor-root bursts of Xenopus, to the long-cycle-period,
      long-motor-root bursts of Rana, which are more typical of adult patterns. 2.
      Local strychnine application had no significant effect on the gross pattern of
      swimming; episode duration and the burst duration in rostral ventral roots away
      from the application site were unaltered, and left-right alternation was
      preserved. We have therefore been able to examine the effects of inhibition on
      individual neurons, uninfluenced by overall changes in the operation of the
      swimming neural circuitry. 3. In all cases strychnine blocked midcycle inhibition
      and significantly increased the peak on-cycle depolarization during swimming. In
      Rana, Bufo, and Triturus motoneurons, and in Xenopus interneurons, strychnine
      significantly increased the reliability of firing during swimming. In Xenopus
      motoneurons, where spiking was 100% reliable anyway, the timing of the spikes was
      advanced relative to rostral ventral root activity. These results do not provide
      support for postinhibitory rebound as a factor in the spike-generating process
      during swimming. In addition to midcycle inhibition, Xenopus motoneurons can also
      show a smaller, additional on-cycle inhibition that is blocked by strychnine. 4.
      In both Rana and Bufo the duration of caudal ventral root bursts close to the
      site of drug application was increased by strychnine, showing that the increased
      motoneuron reliability not only leads to more intense, but also more extensive,
      ventral root activity. 5. At the level of single neurons, glycinergic inhibition
      effectively reduces on-cycle excitation and in turn controls the reliability,
      extent, and precise timing of motoneuron firing. These changes may be the
      individual components underlying broader effects of inhibition described
      previously, such as locomotor frequency control. They also show how any
      modulation of inhibition in localized regions of the spinal cord could produce
      localized control of neuronal firing properties.

PMID- 8871218
TI  - Spontaneous release of GABA activates GABAB receptors and controls network
      activity in the neonatal rat hippocampus.
AB  - 1. We investigated the effects of the selective gamma-aminobutyric acid-B (GABAB)
      receptor antagonist, P-3 aminopropyl-P-diethoxymethyl phosphoric acid (CGP
      35348), on spontaneous and evoked postsynaptic potentials (PSPs) and currents
      (PSCs) in CA3 pyramidal cells and interneurons of hippocampal slices obtained
      between postnatal day 3 and 7 with the use of intracellular and whole cell
      recording techniques. The intracellular pipette solution contained either 2 M
      CsCl or 50 mM 2(triethylamino)-N-(2,6-dimethylphenyl) acetamine (QX314) dissolved
      in 2 M KMeSO4. Cesium and QX314 block postsynaptic responses mediated by GABAB
      receptors. 2. Under control conditions, bath application of CGP 35348 (0.5-1 mM)
      progressively increased the duration of spontaneous and evoked polysynaptic giant
      GABAergic PSPs leading to the appearance of ictal-like discharges. The effects of
      CGP 35348 were dose dependent and voltage independent. 3. In CA3 pyramidal
      neurons, CGP 35348 (0.5 mM) had no effect on monosynaptic GABAergic inhibitory
      PSPs (IPSPs) that were isolated in the presence of ionotropic glutamate receptor
      antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)2
      amino-5-phosphovaleric acid (D-APV, 50 microM). Similarly, CGP 35348 (0.5 mM) had
      no effect on monosynaptic glutamatergic excitatory PSPs (EPSPs) that were
      isolated in the presence of bicuculline (10 microM) and high divalent cation
      artificial cerebrospinal fluid (ACSF; 6 mM Mg2+/4 mM Ca2+). 4. In CA3 pyramidal
      neurons exposed to CNQX (20 microM) and D-APV (50 microM), application of the
      potassium channel blocker 4-aminopyridine (4-AP, 50 microM) generated synchronous
      giant GABAergic PSPS that were blocked in the presence of high divalent cation
      ACSF (6 mM Mg2+/4 mM Ca2+) or bicuculline (10 microM). The duration of these
      synchronous GABAergic PSPs was prolonged in the presence of CGP 35348 (0.5 mM)
      but did not lead to the appearance of ictal-like discharges. 5. In the presence
      of bicuculline, interictal giant glutamatergic potentials were observed in
      simultaneously recorded CA3 pyramidal cells and interneurons. CGP 35348 (0.5 mM)
      progressively increased the duration of these bicuculline-induced glutamatergic
      bursts leading to the simultaneous appearance of ictal discharges in both
      pyramidal cells and interneurons. 6. These results suggest that in the neonatal
      CA3 hippocampal region, when synchronous giant polysynaptic GABAergic PSPs are
      present (i.e., under basal, control conditions), spontaneously released GABA
      reaches a critical level and activates GABAB receptors on both pyramidal cells
      and interneurons thus regulating the level of glutamatergic and GABAergic
      activity in the CA3 neuronal network.

PMID- 8871219
TI  - Presynaptic inhibition of exteroceptive afferents by proprioceptive afferents in
      the terminal abdominal ganglion of the crayfish.
AB  - 1. Exteroceptive hairs that are sensitive to water displacement and touch are
      distributed over the surface of the tailfan of crayfish. We show that the sensory
      neurons innervating these hairs receive a primary afferent depolarization (PAD)
      from sensory neurons innervating a proprioceptor that monitors movements of the
      endopodite and protopodite of the tailfan. This PAD occurs only during high
      velocity movements of the exopodite, which are similar to those that occur during
      swimming. The effects that the proprioceptor mediate are widespread, so that
      afferents in four sensory nerve roots of the terminal abdominal ganglion,
      innervating hairs on the protopodite, exopodite, endopodite, and telson, receive
      a PAD. The PAD is unlikely to be mediated through monosynaptic pathways because
      there is no anatomic overlap between the central projections of chordotonal
      afferents and many of the exteroceptive afferents. The depolarization is
      associated with a conductance increase and can be increased by the injection of
      hyperpolarizing current or reversed (approximately 10 mV above resting potential)
      by injection of depolarizing current. The properties of the presynaptic input
      are, therefore, consistent with being mediated through chemical synapses. This is
      supported by the observation in the electron microscope that the exteroceptive
      afferents receive chemical input synapses. The depolarization is mimicked by
      gamma-aminobutyric acid and reduced by bath application of picrotoxin or
      bicuculline, suggesting that it is a depolarizing inhibitory postsynaptic
      potential. The PAD reduces the amplitude of exteroceptive afferent spikes, an
      action that is thus likely to reduce transmitter release and the efficacy of
      synaptic transmission.

PMID- 8871220
TI  - Role of GABA in shaping frequency tuning and creating FM sweep selectivity in the
      inferior colliculus.
AB  - 1. We examined the role of gamma-aminobutyric acid (GABA)-mediated inhibition in
      shaping excitatory tuning curves and creating selectivity for frequency-modulated
      (FM) sweeps in 29 neurons in the central nucleus of the inferior colliculus (ICC)
      of the pallid bat, with the use of single-unit recording coupled with the
      iontophoretic application of bicuculline methiodide (BIC), an antagonist of GABAA
      receptors. 2. BIC increased response magnitude 2 to 6 times over pretreatment
      levels in > 80% of neurons tested, and converted > 50% of nonmonotonic intensity
      rate functions to monotonic or plateaued functions, demonstrating that GABAergic
      input normally limited response magnitude and inhibited responses at higher
      intensities. BIC typically had little effect on response thresholds, except in
      more specialized neurons that normally responded poorly to tones. In these cases,
      BIC disinhibited the neurons' responses to tones and lowered excitatory
      thresholds as much as 25 dB. 3. We examined the effects of BIC application on
      both excitatory and inhibitory tuning curves (measured with simultaneous 2-tone
      inhibition) to determine whether inhibitory curves were GABA mediated and whether
      removal of this inhibition was accompanied by an expansion of the excitatory
      curve. BIC had variable effects on the width of excitatory curves. In most cases,
      excitatory curves were at least slightly broadened, and expanded into regions
      previously occupied by inhibitory curves. In most cases, excitatory curves were
      at least slightly broadened, and expanded into regions previously occupied by
      inhibitory curves. However, in a few cases, inhibitory curves could be eliminated
      without an expansion of the excitatory curve. The greatest effect was seen in
      neurons with closed excitatory tuning curves; blocking GABAergic input caused the
      curves to open, allowing the neurons to respond at higher intensities. 4.
      Approximately 50% of the neurons in the ICC tuned to the spectrum of the bat's
      downward FM sweeping biosonar pulse respond preferentially to downward FM sweeps
      and not to upward sweeps, tones, or noise. In all neurons tested, BIC at least
      partially destroyed selectivity for sweep direction. This destruction could
      occur, however, without a loss of response exclusivity; in some cases, the
      neurons still did not respond to tones or noise. These results suggest that
      response selectivity for a species-specific signal is created by GABAergic input
      to ICC neurons. These results are used to suggest a mechanism that creates
      selectivity for FM sweep direction.

PMID- 8871221
TI  - Developmental changes in membrane properties and postsynaptic currents of granule
      cells in rat dentate gyrus.
AB  - 1. Whole cell patch-clamp recordings were used to study dentate gyrus granule
      cells in hippocampal slices from juvenile rats (postnatal days 8-32). Membrane
      properties were measured with the use of current-clamp recordings and were
      correlated with the morphology of a subgroup of neurons filled with biocytin. The
      components of the postsynaptic currents (PSCs) induced by medial perforant path
      stimulation were characterized with the use of specific receptor antagonists in
      voltage-clamp recordings. 2. Granule cells located in the middle third of the
      superior blade of stratum granulosum from the rostral third of hippocampus were
      divided into three groups according to their input resistance (IR). Neurons with
      low IR (206 +/- 182 M omega, mean +/- SD) had hyperpolarized resting membrane
      potentials (-82 +/- 7 mV) and high-amplitude action potentials (108 +/- 23 mV).
      Neurons were high IR (1,259 +/- 204 M omega) had more depolarized resting
      membrane potentials (-54 +/- 6 mV) and lower-amplitude action potentials (71 +/-
      10 mV). Neurons with intermediate IR (619 +/- 166 M omega) also had intermediate
      resting membrane potentials (-63 +/- 7 mV) and action potential amplitudes (86 +/
      14 mV). Low-IR neurons became increasingly prevalent with advancing postnatal
      age, but neurons from each group could be found throughout the entire period
      under study. 3. Morphological studies of low-IR neurons revealed an extensive
      dendritic arborization that traversed the entire molecular layer and was
      characteristic of mature granule cells. High-IR cells had smaller somata and
      short, simple dendritic arborization that incompletely penetrated the molecular
      layer and were classified as immature. Intermediate-IR cells had morphological
      features of intermediate maturity. 4. The initial phase of the PSC evoked at -80
      mV was a fast inward current that was comparable with respect to latency to peak,
      latency to onset, and 10-90% rise time in neurons of all maturities held at -80
      mV. This current was 6-cyano-7-nitroquinoxaline-2,3-dione sensitive. 5. The decay
      phases of PSCs at -80 mV varied with neuronal maturity. Mature neurons had
      monoexponential decays (tau = 8.9 +/- 3.6). Intermediate and immature neurons had
      prominent later inward currents that resulted in slower decays. In the case of
      the immature neurons, the inward current during the decay phase could be
      separated from the initial fast inward peak. The later inward currents in
      intermediate and immature neurons were bicuculline sensitive. 6. With the use of
      uniform ionic conditions of the extracellular and patch solutions, current
      voltage relations and reversal potentials for pharmacologically isolated alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate
      (NMDA), and gamma-aminobutyric acid-A (GABAA) currents were comparable across all
      cell maturities. Calculated ratios for peak GABAA/NMDA/AMPA currents decreased
      significantly with maturation as follows: 9.4 +/- 2.9/1.4 +/- 0.5/1.0 for
      immature cells, 7.2 +/- 2.5/1.5 +/- 0.7O/1.0 for intermediate cells, and 2.0 +/-
      1.2/0.9 +/- 0.4/1.0 for mature cells. 7. GABA current was mediated both by
      polysynaptic activation of interneurons and by direct activation of interneurons
      with monosynaptic input onto granule cells. The proportional contributions of
      mono- and polysynaptic GABA to total GABA were comparable across all cell
      maturities; latency to peak GABA current decreased with increasing cell maturity
      for both mono- and polysynaptic components. 8. We conclude that PSCs evoked in
      granule cells by medial perforant path activation in neurons of all maturities
      consist of both glutamatergic and GABAergic components. PSCS are dominated by
      GABAergic neurotransmission in immature granule cells, and the contribution of
      glutamatergic neurotransmission increases with neuronal maturation. The greater
      ratio of peak GABAA to glutamate currents and the longer time interval between
      their respective peaks combine to produce a distinctive PSC shape

PMID- 8871222
TI  - A comparison of spontaneous EPSCs in layer II and layer IV-V neurons of the rat
      entorhinal cortex in vitro.
AB  - 1. We have compared the characteristics of spontaneous excitatory postsynaptic
      currents (sEPSCs) in neurons of layer IV-V and layer II of the rat entorhinal
      cortex (EC) using whole cell voltage-clamp recordings in a slice preparation. 2.
      The frequency of sEPSCs was similar in the two layers, but the events in layer IV
      V had a larger mean amplitude, faster rise time, and were faster to decay. The
      difference in amplitude could be attributed to the presence of a population of
      larger events in the layer IV-V neurons that were not present in layer II. 3.
      Electrotonic length was greater in layer II neurons, suggesting that the
      difference in kinetics of the sEPSCs may be explained partly by electrotonic
      attenuation. 4. The frequency of sEPSCs in both layers was reduced by
      tetrodotoxin (TTX) to a similar extent (15-20%). However, the amplitude
      distribution was unchanged in layer II, whereas in layer IV-V TTX abolished most
      of the larger amplitude sEPSCs. 5. 6-cyano-7-nitroquinoxaline-2,3-dione or 6
      nitro-7-sulphamoylbenzo (f)-quinoxaline-2,3-dione, abolished most of the sEPSCs
      in neurons of both layers. However, even at negative holding potentials, a
      population of slower time-course sEPSCs remained in the presence of these
      antagonists. 6. The slow sEPSCs were more frequent in layer IV-V but had similar
      characteristics in both layers, being increased in amplitude at more positive
      holding potentials or in Mg2+-free medium, and blocked by 2-amino-5
      phosphonovalerate (AP5). 7. AP5 alone (i.e., without addition of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid antagonists) reduced the peak
      amplitude and decay phase of sEPSCs in layer IV-V neurons but appeared to have
      little effect on amplitude and only a weak effect on decay phase in layer II. 8.
      Thus both layer IV-V and layer II neurons of the EC suffer continuous spontaneous
      excitation. However, layer IV-V neurons exhibit larger amplitude sEPSCs, probably
      mediated by release of multiple quanta of neurotransmitter. In addition, although
      both types of neurons display spontaneous excitation mediated by N-methyl-D
      aspartate receptors, this component appears more pronounced in the deeper layers.

PMID- 8871223
TI  - NMDA-receptor-mediated synaptic currents in guinea pig laterodorsal tegmental
      neurons in vitro.
AB  - 1. Whole cell voltage-clamp techniques were used to record glutamate-receptor
      mediated synaptic currents from neurons of the laterodorsal tegmental nucleus
      (LDT). The principal cells of the LDT contain acetylcholine and nitric oxide
      synthase, and are believed to be involved in the control of sleep-waking behavior
      via widespread projections to the thalamus and brain stem. LDT cells were
      recorded from slices of mature guinea pig brain stem with patch pipette solutions
      containing cesium as the primary cation. 2. Application of N-methyl-D-aspartate
      (NMDA) elicited currents that were strongly voltage dependent with a mean
      reversal potential of +16.3 mV. Peak currents occurred near -15 mV, and a region
      of negative slope conductance was seen at more negative potentials. Application
      of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid evoked currents that
      exhibited a nearly linear current-voltage relation with a mean reversal potential
      of -3.4 mV. 3. Electrical stimulation of local afferents elicited dual-component
      excitatory postsynaptic currents (EPSCs) with decays that were well fitted by the
      sum of two exponentials. Mean decay time constants at -60 mV were 8.77 ms for the
      faster component and 129.4 ms for the slower component. The faster component
      displayed a linear current-voltage relation and was blocked by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) or 6,7-dinitroquinoxaline-2,3-dione, indicating
      that it was mediated by non-NMDA receptors, whereas the slower component
      displayed a voltage dependence similar to that for NMDA-evoked currents and was
      blocked by 2-amino-5-phosphonopentanoic acid (AP-5), indicating its mediation by
      NMDA receptors. 4. The fractional contribution of NMDA receptors to the EPSC was
      estimated from double-exponential curve fits to the decay phases. With this
      method, NMDA receptors were estimated on average to carry 10.1% of the total peak
      EPSC at -60 mV. Blockade of the non-NMDA-receptor-mediated component with CNQX
      revealed a residual EPSC whose amplitude was 14.4% of the control value, whereas
      AP-5 alone reduced the control EPSC peak by 16.1%, both values were comparable
      with those obtained from curve fit estimates. 5. Previous work has shown that the
      presence of 4-aminopyridine-sensitive, A-like transient current in LDT cells is
      correlated with the cholinergic phenotype. The majority of cells in this study
      exhibited A-like transient currents that were blocked by 4-amino-pyridine,
      suggesting that the majority of the data were obtained from the cholinergic and
      NOS-containing neurons of the LDT nucleus. 6. These experiments demonstrate the
      synaptic activation of functional NMDA and non-NMDA receptors in LDT neurons, and
      indicate that NMDA receptors contribute to fast excitatory transmission in these
      cells. The results suggest that afferents releasing excitatory amino acids may
      play an important role in controlling the state-dependent activity of LDT
      neurons.

PMID- 8871224
TI  - Soleus stretch reflex modulation during gait in humans.
AB  - 1. The modulation of the short-latency stretch reflex during walking at different
      walking speeds was investigated and compared with the stretch reflex during
      standing in healthy human subjects. 2. Ankle joint stretches were applied by a
      system able to rotate the human ankle joint during treadmill walking in any phase
      of the step cycle. The system consisted of a mechanical joint attached to the
      subject's ankle joint and connected to a motor placed beside the treadmill by
      means of bowden wires. The weight of the total system attached to the leg of the
      subject was 900 g. 3. The short-latency soleus stretch reflex was modulated
      during a step. In the stance phase, the amplitude equaled that found during
      standing at matched soleus background electromyogram (EMG). In the transition
      from stance to swing, the amplitude was 0 in all subjects. In late swing, the
      stretch reflex amplitude increased to 45 +/- 27% (mean +/- SD) of the maximal
      amplitude in the stance phase (stretch amplitude 8 degrees, stretch velocity 250
      degrees/s). 4. The onset (42 +/- 3.2 ms) and peak latencies (59 +/- 2.5 ms) of
      the stretch reflex did not depend on the phase in the step cycle at which the
      reflex was elicited. 5. When the ankle joint is rotated, a change in torque can
      be measured. The torque measured over the first 35 ms after stretch onset
      (nonreflex torque) was at a maximum during late stance, when the leg supported a
      large part of the body's weight, and at a minimum during the swing phase. At heel
      contact the nonreflex torque was 50% of its maximal value. 6. During the stance
      phase the maximal EMG stretch reflex had a phase lead of approximately 120 ms
      with respect to the maximal background EMG and a phase lead of approximately 250
      ms with respect to the maximal nonreflex torque. 7. The constant latency of the
      stretch reflex during a step implied that the ankle extensor muscle spindles are
      always taut during walking. 8. The relatively high amplitude of the stretch
      reflex in late swing and at heel contact made it likely that the stretch reflex
      contributed to the activation of the ankle extensor muscles in early stance
      phase.

PMID- 8871225
TI  - Potassium currents and membrane excitability of neurons in the rat's dorsal
      nucleus of the lateral lemniscus.
AB  - 1. The contribution of voltage-activated outward potassium currents to membrane
      excitability of neurons in the rat's dorsal nucleus of the lateral lemniscus
      (DNLL) was studied in a brain slice preparation using whole cell patch-clamp and
      intracellular recordings. Voltage-clamp methods and pharmacological manipulations
      were used to examine the currents regulating membrane dynamics in DNLL. 2. A
      delayed sustained outward current was evoked by applying depolarizing voltage
      steps across the cell membrane from a holding potential of -50 mV. An additional
      transient outward current was evoked when the depolarizing steps were preceded by
      a hyperpolarizing prepulse of -110 or -120 mV. 3. The transient outward current
      peaked within 6.8 ms of the onset of a depolarizing pulse. It decayed with a time
      constant of 12.3 ms for a 60-mV depolarizing voltage shift. Half-inactivation of
      this current occurred at -81.3 mV. The time constant for removal of the
      inactivation was 17.4 ms. The transient current had a high sensitivity to 4
      aminopyridine (4-AP). 4. The sustained current was activated more slowly and was
      more sensitive to tetraethylammonium (TEA) than the transient current. The
      sustained current had both Ca2+-dependent and Ca2+-independent components. The
      Ca2+-dependent portion emerged at potentials of about -35 mV and was activated
      fully at +10 mV. The Ca2+-independent component was activated at potentials more
      positive than -40 mV and increased in magnitude with further depolarization.
      Inactivation of the Ca2+-independent component was voltage dependent. Also, TEA
      suppressed the Ca2+-independent compound. 5. The transient current in DNLL
      neurons closely resembled the A current (IA) described for hippocampal and other
      neurons in both kinetics and pharmacology. The Ca2+-independent component of the
      sustained current resembled the K current (IK) described for other neurons in
      both its properties of activation and inactivation and its pharmacology. 6. The
      outward current of some DNLL neurons was found to contain a dendrotoxin-sensitive
      component. This component reached its peak at 6.8 ms and had voltage-sensitive
      time constants of decay of 25.5 and 8.5 ms with voltage steps of 40 and 60 mV,
      respectively. 7. Application of 4-AP and TEA markedly prolonged the spike width,
      abolished the fast component of the after hyperpolarization and depolarized the
      cell membrane. Also, the number of action potentials produced by positive current
      injection increased under the influence of 4-AP and TEA. Membrane excitability
      and spike repolarization were dependent on both 4-AP-sensitive transient and TEA
      sensitive sustained currents. 8. Neurons in DNLL typically exhibit a steady
      discharge of action potentials in response to sustained membrane depolarization.
      The rate and temporal pattern of production of action potentials in these cells
      are determined by the combination of transient and sustained potassium channels.

PMID- 8871226
TI  - Self-moved target eye tracking in control and deafferented subjects: roles of arm
      motor command and proprioception in arm-eye coordination.
AB  - 1. When a visual target is moved by the subject's hand (self-moved target
      tracking), smooth pursuit (SP) characteristics differ from eye-alone tracking: SP
      latency is shorter and maximal eye velocity is higher in self-moved target
      tracking than in eye-alone tracking. The aim of this study was to determine which
      signals (motor command and/or proprioception) generated during arm motion are
      responsible for the decreased time interval between arm and eye motion onsets in
      self-moved target tracking. 2. Six control subjects tracked a visual target whose
      motion was generated by active or passive movements of the observer's arm in
      order to determine the role played by arm proprioception in the arm-eye
      coordination. In a second experiment, the participation of two subjects suffering
      complete loss of proprioception allowed us to assess the contribution of arm
      motor command signals. 3. In control subjects, passive movement of the arm led to
      eye latencies significantly longer (130 ms) than when the arm was actively self
      moved (-5 ms:negative values meaning that the eyes actually started to move
      before the target) but slightly shorter than in eye-alone tracking (150 ms).
      These observations indicate that active movement of the arm is necessary to
      trigger short-latency SP of self-moved targets. 4. Despite the lack of
      proprioceptive information about arm motion, the two deafferented subjects
      produced early SP (-8 ms on average) when they actively moved their arms. In this
      respect they did not differ from control subjects. Active control of the arm is
      thus sufficient to trigger short-latency SP. However, in contrast with control
      subjects, in deafferented subjects SP gain declined with increasing target motion
      frequency more rapidly in self-moved target tracking than in eye-alone tracking.
      5. The deafferented subjects also tracked a self-moved target while the
      relationship between arm and target motions was altered either by introducing a
      delay between arm motion and target motion or by reversing target motion relative
      to arm motion. As with control subjects, delayed target motion did not affect SP
      latency. Furthermore, the deafferented subjects adapted to the reversed arm
      target relationship faster than control subjects. 6. The results suggest that arm
      motor command is necessary for the eye-to-arm motion onset synchronization,
      because eye tracking of the passively moved arm was performed by control subjects
      with a latency comparable with that of eye-alone tracking of an external target.
      On the other hand, as evidenced by the data from the deafferented subjects,
      afferent information does not appear to be necessary for reducing the time
      between arm motion and SP onsets. However, afferent information appears to
      contribute to the parametric adjustment between arm motor command and visual
      information about arm motion.

PMID- 8871227
TI  - Discrimination of simulated texture patterns on the human hand.
AB  - 1. Textures formed by periodic dot arrays are defined by the dot density,
      spacing, and angular orientation with respect to the direction of motion. In this
      report we evaluate the effects of the dot density (intensive cues) and
      arrangement (spatial cues) on the ability of human subjects to discriminate
      texture patterns scanned across an OPTACON tactile stimulator that selective
      stimulates rapidly adapting cutaneous mechanoreceptors. We compared dot arrays
      arranged on the index finger in specific patterns (horizontal, vertical, diamond,
      up diagonal, or down diagonal orientation) and spaced 4.8, 7.2, or 9.6 mm apart
      (high, medium, and low density) with the use of a two-alternative forced-choice
      protocol. 2. Textures are well discriminated when their elements are tightly
      spaced along one axis and widely spaced on all other axes. Humans distinguish
      textures that differ only in orientation with mean accuracy of 75% at low density
      and 65% at medium density, but discriminate high-density textures poorly (mean
      accuracy = 48%). Accuracy is related to the angular disparity between patterns,
      and to similarity of spacing and orientation along major and minor axes of the
      arrays. Vertical and horizontal patterns are more accurately distinguished than
      the oblique ones, and diamond arrays are the least well discriminated. Diagonal
      and diamond textures are often confounded, and the up and down diagonal patterns
      are confused with each other particularly as the texture density rises. The
      preference for the vertical and horizontal patterns may relate to an interaction
      between the orientation axis of the texture and its direction of motion across
      the skin. 3. Intensive cues provided by the total number of applied stimuli
      supplement the spatial cues inherent to the pattern orientation, because textures
      that differ in both spacing and orientation are discriminated better than those
      that differ only in orientation or spacing. Mean accuracy ranges from 96% for
      comparisons of high- and low-density textures, which differ in the total number
      of dots by a factor of 2, to 80% when medium-density patterns are compared with
      high- or low-density textures. 4. Textures that differ in density but not in
      orientation are less well discriminated than those of different orientation. For
      example, 82% of patterns that differ in both density and orientation are
      distinguished correctly in pairings of low- and medium-density textures, whereas
      those that differ only in density are discriminated correctly on 45% of trials.
      Subjects seem to use spatial rather than intensive cues when discriminating
      patterns of similar density, suggesting that the similarity of form (the spatial
      arrangement of the closely spaced dots) is more readily apparent than small
      differences in spacing along the axis of motion. 5. Subjects are most most
      successful in differentiating texture patterns when they are able to mentally
      picture the orientation and spacing of the pattern. We found a strong correlation
      between the subjects' ability to discriminate textures of a given spacing and
      their ability to identify the specific texture by matching it to the appropriate
      visual representation. Subjects are able to identify correctly all five
      orientations at low and medium densities, with mean accuracy of 76%, but
      recognize only the vertical arrays when high-density patterns are presented. The
      ability to image the textures is noteworthy, because subjects received no
      feedback about performance. 6. Spatial imaging of textures appears limited by the
      diameter of cutaneous receptive fields on the hand. We propose that the
      structural axis of a regular texture array results from perceptual linkage of
      adjacent elements along one principal axis by continuous bands of neural activity
      when their spacing is smaller than the receptive field diameter.(ABSTRACT
      TRUNCATED)

PMID- 8871228
TI  - GABAB receptors presynaptically modulate excitatory synaptic transmission in the
      rat supraoptic nucleus in vitro.
AB  - 1. The effect of gamma-aminobutyric acid-B (GABAB)-receptor activation on
      excitatory synaptic transmission in the rat supraoptic nucleus (SON) was examined
      using the nystatin perforated-patch whole cell recording technique in coronal
      hypothalamic slices. 2. Stimulation of the hypothalamic region dorso-medial to
      the SON elicited glutamate and GABAA-receptor-mediated synaptic responses in
      electrophysiologically identified magnocellular neurosecretory cells. 3. Bath
      application of the GABAB-receptor agonist, +/- -baclofen reversibly reduced
      pharmacologically isolated, glutamate-mediated excitatory postsynaptic currents
      (EPSCs) in a concentration-dependent manner. At the concentrations used, baclofen
      altered neither the postsynaptic conductances of these cells nor their response
      to bath applied alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA).
      4. The baclofen-induced synaptic depression was accompanied by an increase in
      paired pulse facilitation (PPF). This increase in PPF, as well as the synaptic
      depression, was blocked by the GABAB-receptor antagonists CGP36742 and saclofen.
      5. In addition to blocking the actions of baclofen in this nucleus, CGP36742
      caused an increase in the evoked EPSC amplitude without altering postsynaptic
      cell conductances or responses induced by bath-applied AMPA. Contrary to the
      action of CGP36742, saclofen caused a baclofen-like depression of the evoked
      EPSC, suggesting that it may act as a partial GABAB receptor agonist. 6. These
      results indicate that the activation of presynaptic GABAB receptors reduces fast
      excitatory synaptic transmission in the SON. They further suggest that
      presynaptic GABAB receptors may be tonically activated in vitro. Thus GABAB
      receptors may influence the level of activity and excitation of SON neurons and
      hence modulate the secretion of the regulatory neuropeptides vasopressin and
      oxytocin.

PMID- 8871229
TI  - Isolation and characterization of a persistent potassium current in neostriatal
      neurons.
AB  - 1. Depolarization-activated, calcium-independent potassium (K+) currents were
      studied with the use of whole cell voltage-clamp recording from neostriatal
      neurons acutely isolated from adult (> or = 4 wk old) rats. The whole cell K+
      current was composed of transient and persistent components. The aims of the
      experiments were to isolate the persistent component and then to characterize its
      voltage dependence and kinetics. 2. Application of 10 mM 4-aminopyridine (4-AP)
      completely blocked the transient currents while reducing the persistent current
      by approximately 40% [50% inhibitory concentration (IC50), of blockable current =
      125 microM]. The persistent K+ current also was reduced by tetraethylammonium
      (TEA). Two components to the TEA block were present, having IC50s of 125 microM
      (23% of the blockable current) and 5.9 mM (77% of the blockable current).
      Collectively, these results suggested that the persistent components of the total
      K+ current was pharmacologically heterogeneous. The properties of the 4-AP
      resistant, persistent K+ current (IKrp) were subsequently studied. 3. The
      kinetics of activation and deactivation of IKrp were voltage dependent.
      Examination of the entire activation/deactivation time constant profile showed
      that it was bell shaped, with time constants being moderately rapid (tau
      approximately 50 ms) at membrane potentials corresponding to the resting
      potential of neostriatal cells (approximately -80 mV), becoming considerably
      longer (tau approximately 100 ms) at potentials near the cells' spike thresholds
      (approximately -45 mV), and decreasing to a minimum (tau approximately 5 ms) at
      potentials associated with the peak of the cells' action potentials
      (approximately +20 mV). The inactivation kinetics of IKrp also were voltage
      dependent. The time constants of inactivation varied between 1 and 8 s at
      potentials between -10 and +35 mV. 4. Unlike persistent K+ currents in many other
      cell types, IKrp activated at relatively hyperpolarized membrane potentials
      (approximately -70 mV). The Boltzmann function describing activation had a half
      activation voltage of -13 mV and a slope factor of 12 mV. In addition, the
      Boltzmann function describing the voltage dependence of inactivation of IKrp had
      a relatively depolarized half-inactivation voltage of -55 and a large slope
      factor of 19 mV, indicating that this current was available over a broad range of
      membrane potentials (between -100 and -10 mV). 5. Neostriatal neurons recorded in
      vivo exhibit subthreshold shifts in membrane potential of variable duration (tens
      of ms to s) from a hyperpolarized resting state to a depolarized state that is
      limited in amplitude just below spike threshold. The voltage dependence of
      activation and inactivation of IKrp indicates that it will be available on
      depolarization from the hyperpolarized state. However, the slow activation rate
      of this current suggests that it will contribute little either to limiting the
      amplitude of the initial depolarization associated with entry into the
      depolarized state or to depolarizing episodes of short duration (e.g., < 50 ms).
      However, IKrp should limit the amplitude of membrane depolarizations associated
      with prolonged excursions into the depolarized state.

PMID- 8871230
TI  - Inward currents underlying action potentials in rat adrenal chromaffin cells.
AB  - 1. Current- and voltage-clamp studies were conducted on isolated rat adrenal
      chromaffin cells to identify the voltage-dependent ion channels mediating inward
      currents. 2. Mean resting membrane potential of the isolated cells was -62 +/- 3
      (SE) mV. Evoked action potentials were both Na+ and Ca2+ based, and whole cell
      voltage-clamp studies in normal saline revealed an inward-rectifier-type current.
      3. Na+ channels were studied in isolation and showed a half-inactivation of -60
      +/- 2 mV with a slope factor of -6 mV and a half-activation of -26.8 +/- 2 mV
      with a slope factor of 6.5 +/- 0.7 mV. 4. Isolated Ca2+ currents, elicited in 10
      mM external Ca2+, revealed a T-type current in a subset of cells. Ca2+ currents
      were sensitive to both N- and L-type channel antagonists, and blockade of the
      current by the L-type channel antagonist nimodipine and the N-type channel
      antagonist omega-conotoxin GVIA revealed a third Ca2+-current component that was
      unaffected by the P-type channel antagonist omega-agatoxin IVA. 5. Ca2+ currents
      were facilitated 5-20% by a depolarizing prepulse, and facilitation was
      completely blocked by nimodipine. The effects of the dihydropyridine L-type
      channel agonist, (+)202-791 and depolarizing prepulses on the currents were
      additive. 6. The results of this study show that the properties of voltage
      dependent ion channels in rat chromaffin cells differ from those reported in
      their counterparts in bovine chromaffin cells. Na+ channels differ in activation
      and inactivation properties and Ca2+ channels differ in activation, sensitivity
      to antagonists, and the magnitude of voltage-dependent facilitation.

PMID- 8871231
TI  - Is the regulation of the center of mass maintained during leg movement under
      microgravity conditions?
AB  - 1. Investigations on stance regulation have already suggested that the body's
      center of mass is the variable controlled by the CNS to maintain equilibrium. The
      aim of this study was to determine how the center of mass of the body is
      regulated when leg movements are made under different gravitoinertial force
      conditions. 2. Kinematic and electromyographic (EMG) recordings were made during
      both straight-and-level flight (earth-normal gravity condition, nG) and periods
      of weightlessness in parabolic flight (microgravity condition, microG). The
      standing subjects were restrained to the floor (kept from floating away in
      microG) and were instructed to raise one leg laterally to an angle of 45 degrees
      as fast as possible. 3. Two modes of center of mass (CM) control were identified
      during leg movement in nG: a "shift mode" and a "stabilization mode." The shift
      mode served to transfer the CM toward the supporting side before the leg raising,
      and it preceded the phase of single limb support. The stabilization mode took
      place after the CM shift was completed and was aimed at stabilizing the CM during
      raising of the leg. In this phase, the movement of the raising leg is
      counterbalanced by a lateral inclination of the trunk in the opposite direction.
      As a consequence, CM position did not change with respect to the position reached
      before the leg raising, and its projection on the ground remained within the
      support area delineated by the stance foot. 4. Under microG, the CM position did
      not change before the leg raising. Moreover, gastrocnemius medialis activity
      observed in the moving leg under nG, preceding the initiation of the body weight
      transfer toward the supporting leg, was greatly reduced. While the leg is
      raising, the simultaneous and opposite lateral trunk movement was still present
      in microG. 5. Results suggest that the body weight transfer corresponding to the
      shift mode, might depend on the gravity constraints, whereas the stabilization
      mode, which remains unchanged in microG, might be a motor stereotype that does
      not depend on the gravity conditions.

PMID- 8871232
TI  - Central modulation of stretch receptor neurons during fictive locomotion in
      lamprey.
AB  - 1. In lamprey, stretch receptor neurons (SRNs), also referred to as edge cells,
      are located along the lateral margin of the spinal cord. They sense the lateral
      movements occurring in each swim cycle during locomotion. The isolated lamprey
      spinal cord in vitro was used to investigate the activity of SRNs during fictive
      locomotion induced by bath-applied N-methyl-D-aspartate (NMDA). Intracellular
      recordings with potassium acetate filled electrodes showed that 63% of SRNs had a
      clear locomotor-related modulation of their membrane potential. 2. Of the
      modulated SRNs, two-thirds had periods of alternating excitation and inhibition
      occurring during the ipsilateral and the contralateral ventral root bursts,
      respectively. The phasic hyperpolarization could be reversed into a depolarizing
      phase after the injection of chloride ions into the cells; this revealed a
      chloride-dependent synaptic drive. The remaining modulated SRNs were inhibited
      phasically during ipsilateral motor activity. 3. Experiments with barriers
      partitioning the recording chamber with the spinal cord into three pools, allowed
      an inactivation of the locomotor networks within one pool by washing out NMDA
      from the pool in which the SRN was recorded. This resulted in a marked reduction,
      but not an abolishment, of the amplitude of the membrane potential oscillations.
      Both the excitatory and the inhibitory phases were reduced, resulting from
      removal of input from inhibitory and excitatory interneurons projecting from the
      adjacent pools. If the glycine receptor antagonist strychnine (1 microM) was
      applied in one pool, the phasic hyperpolarizing phase disappeared without
      affecting the excitatory phase. 4. Bath application of the gamma-aminobutyric
      acid (GABA)A receptor antagonist, bicuculline (50-100 microM) blocked the
      spontaneous large unitary inhibitory postsynaptic potentials, which occurred
      without a clear phasic pattern. Bicuculline had no significant effect on the peak
      to peak amplitude of the locomotor-related membrane potential oscillations. The
      inhibition in SRNs therefore has a dual origin: glycinergic interneurons provide
      phasic inhibition, while the GABA system can exert a tonic inhibition via GABAA
      receptors. 5. These data show that, in addition to the stretch-evoked excitation,
      which SRNs receive during each locomotor cycle, most of them also receive
      excitation from the central pattern generator network during the ipsilateral
      contraction, which may ensure a maintained high level of sensitivity to stretch
      during the shortening phase of the locomotor cycle. This arrangement is analogous
      to the efferent control of muscle spindles exerted by gamma-motoneurons in
      mammals, which as a rule are coactivated with alpha-motoneurons to the same
      muscle (alpha-gamma linkage).

PMID- 8871234
TI  - Representation and integration of multiple sensory inputs in primate superior
      colliculus.
AB  - 1. The properties of visual-, auditory-, and somatosensory-responsive neurons, as
      well as of neurons responsive to multiple sensory cues (i.e., multisensory), were
      examined in the superior colliculus of the rhesus monkey. Although superficial
      layer neurons responded exclusively to visual stimuli and visual inputs
      predominated in deeper layers, there was also a rich nonvisual and multisensory
      representation in the superior colliculus. More than a quarter (27.8%) of the
      deep layer population responded to stimuli from more than a single sensory
      modality. In contrast, 37% responded only to visual cues, 17.6% to auditory cues,
      and 17.6% to somatosensory cues. Unimodal- and multisensory-responsive neurons
      were clustered by modality. Each of these modalities was represented in map-like
      fashion, and the different representations were in alignment with one another. 2.
      Most deep layer visually responsive neurons were binocular and exhibited poor
      selectivity for such stimulus characteristics as orientation, velocity, and
      direction of movement. Similarly, most auditory-responsive neurons had
      contralateral receptive fields and were binaural, but had little frequency
      selectivity and preferred complex, broad-band sounds. Somatosensory-responsive
      neurons were overwhelmingly contralateral, high velocity, and rapidly adapting.
      Only rarely did somatosensory-responsive neurons require distortion of
      subcutaneous tissue for activation. 3. The spatial congruence among the different
      receptive fields of multisensory neurons was a critical feature underlying their
      ability to synthesize cross-modal information. 4. Combinations of stimuli could
      have very different consequences in the same neuron, depending on their temporal
      and spatial relationships. Generally, multisensory interactions were evident when
      pairs of stimuli were separated from one another by < 500 ms, and the products of
      these interactions far exceeded the sum of their unimodal components. Whether the
      combination of stimuli produced response enhancement, response depression, or no
      interaction depended on the location of the stimuli relative to one another and
      to their respective receptive fields. Maximal response enhancements were observed
      when stimuli originated from similar locations in space (as when derived from the
      same event) because they fell within the excitatory receptive fields of the same
      multisensory neurons. If, however, the stimuli were spatially disparate such that
      one fell beyond the excitatory borders of its receptive field, either no
      interaction was produced or this stimulus depressed the effectiveness of the
      other. Furthermore, maximal response interactions were seen with the pairing of
      weakly effective unimodal stimuli. As the individual unimodal stimuli became
      increasingly effective, the levels of response enhancement to stimulus
      combinations declined, a principle referred to as inverse effectiveness. Many of
      the integrative principles seen here in the primate superior colliculus are
      strikingly similar to those observed in the cat. These observations indicate that
      a set of common principles of multisensory integration is adaptable in widely
      divergent species living in very different ecological situations. 5.
      Surprisingly, a few multisensory neurons had individual receptive fields that
      were not in register with one another. This has not been noted in multisensory
      neurons of other species, and these "anomalous" receptive fields could present a
      daunting problem: stimuli originating from the same general location in space
      cannot simultaneously fall within their respective receptive fields, a stimulus
      pairing that may result in response depression. Conversely, stimuli that
      originate from separate events and disparate locations (and fall within their
      receptive fields) may result in response enhancement. However, the spatial
      principle of multisensory integration did not apply in these cases. (ABSTRACT
      TRUNCATED)

PMID- 8871233
TI  - Regenerated dorsal root fibers form functional synapses in embryonic spinal cord
      transplants.
AB  - 1. The aim of the present study was to determine whether synapses formed by
      dorsal root afferents that regenerate into intraspinal transplants of fetal
      spinal cord are functional. Severed L4 or L5 dorsal root stumps were placed at
      the bottom of dorsal quadrant cavities made in the lumbar spinal cords of adult
      rats and juxtaposed to embryonic day 14 spinal cord transplants. 2. In animals
      examined 5-10 weeks later, we recorded extracellularly in transplants from 43
      units that fired in response to electrical stimulation of the implanted dorsal
      root. Latency fluctuations of extracellular firing that increase with stimulus
      and failure to follow high-frequency and posttetanic potentiation of
      extracellular firing stimulation suggest that synapses with conventional
      properties are formed between regenerating afferents and transplant neurons.
      Limited intracellular recordings confirmed the existence of excitatory
      postsynaptic potentials in transplant neurons after dorsal root stimulation. 3.
      In 16 units, extracellular firing occurred in response to single shock
      stimulation. The remainder of the units required two or more dorsal root shocks
      to evoke firing; some of these connections also may be monosynaptic. 4. Under the
      assumption that single shock firing was most likely the result of monosynaptic
      connections between transplant neurons and regenerated dorsal root fibers, we
      estimated the conduction velocities of regenerated fibers. These estimates
      suggest that fibers with conduction velocities in the C, A delta, and A
      alpha/beta ranges regenerate into transplants of embryonic spinal cord. 5. The
      results demonstrate that regenerated dorsal root axons establish functional
      synaptic connections with transplant neurons. The implications for using fetal
      transplants to help rebuild spinal reflex circuits after spinal cord injury are
      considered.

PMID- 8871235
TI  - Characterization of a radula opener neuromuscular system in Aplysia.
AB  - 1. Several lines of evidence suggest that the I7-I10 muscle group contributes to
      the radula opening phase of behavior in Aplysia; 1) extracellular stimulation of
      these muscles in reduced preparations causes the halves of the radula to
      separate, 2) synaptic activity can be recorded from muscles I7-I10 in intact
      animals when the radula is opening, and 3) motor neurons innervating I7-I10 are
      activated out of phase with retractor/closer motor neurons during cycles of
      buccal activity driven by the cerebral-to-buccal interneuron 2 (CBI-2). 2. All of
      the opener muscles are innervated by the B48 neurons, a bilaterally symmetrical
      pair of cholinergic motor neurons. B48 neurons produce excitatory junction
      potentials (EJPs) in opener muscle fibers that summate to produce muscle
      contractions. Contraction size is determined by the size of depolarization in
      muscle fibers and/or by action potentials that are triggered by summation of B48
      evoked EJPs. 3. In addition to input from B48 neurons, opener muscles also
      receive excitatory input from the cholinergic multiaction neurons B4/B5. EJPs
      evoked by stimulation of neurons B4/B5 are 1/10 the size of B48-evoked EJPs.
      Consequently, changes in muscle tension produced by B4/B5 activity are relatively
      small. In contrast to B48 neurons, neurons B4/B5 are likely to be active during
      the closing/retraction phase of behavior. During cycles of buccal activity driven
      by neuron CBI-2, neurons B4/B5 fire in phase with closer/retractor motor neurons.
      Thus opener muscles may develop a modest amount of tension during the
      closing/retraction phase of behavior as a result of synaptic input from neurons
      B4/B5. 4. Opener muscles may also develop tension during closing/retraction
      simply by virtue of the fact that they have been stretched. When isolated opener
      muscles are lengthened, depolarizations are recorded from individual muscle
      fibers, and muscle tension increases. With sufficient changes in fiber length,
      action potentials are elicited. These action potentials produce twitchlike muscle
      contractions that become rhythmic with maintained stretch. Stretch-activated
      depolarizations are generally first apparent when muscle length is increased by 1
      mm. Length changes of 4-5 mm are generally necessary to elicit twitchlike muscle
      contractions. Changes of 1-2 mm in muscle length are observed when the opener
      muscle's antagonist, the accessory radula closer, is activated in reduced
      preparations. 5. Stretch may also modulate B48-induced contractions of the opener
      muscles. When muscle length is increased, B48-elicited contractions of the I7
      muscle are larger. These increases in contraction amplitude are accompanied by
      decreases in contraction latency. 6. We conclude that muscles I7-I10 contract
      vigorously in response to strong excitatory input from neuron B48 and contribute
      to radula opening. Stretch may potentiate this activity. Thus, if radula closer
      muscles contract vigorously and pull on the opener muscles, the opener muscles
      will respond by contracting more vigorously themselves. This may be a mechanism
      for maintaining amplitude relationships between antagonistic muscles.
      Additionally, it is likely that the opener muscles will develop at least a modest
      amount of tension during closure/retraction of the radula. Part of this
      activation may derive from the weak excitatory input that the muscles receive
      from neurons B4/B5. Another part may derive from the stretch. One function of
      this co-contraction may be to act as a brake on closure, bringing this phase of
      feeding behavior to a smooth halt.

PMID- 8871236
TI  - Profound disturbances of pre- and postsynaptic GABAB-receptor-mediated processes
      in region CA1 in a chronic model of temporal lobe epilepsy.
AB  - 1. This report examines alterations in presynaptic and postsynaptic processes
      mediated by gamma-aminobutyric acid-B (GABAB) receptors within hippocampal region
      CA1 in a model of chronic temporal lobe epilepsy (TLE). Intracellular recordings
      were obtained in pyramidal cells from combined hippocampal/parahippocampal
      control slices and slices obtained > or = 1 mo after a period of self-sustaining
      limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation.
      2. Monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked by
      placement of the stimulating electrode in stratum pyramidale within 500 microns
      of the recording electrode in the presence of the ionotropic glutamate receptor
      antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and D(-)-2-amino-5
      phosphonovaleric acid. Control IPSPs exhibited early (GABAA-receptor-mediated)
      and late (GABAB-receptor-mediated) components. In contrast, post-SSLSE IPSPs
      displayed only a GABAA-receptor-mediated IPSP. Post-SSLSE IPSPs were completely
      eliminated by antagonists of the GABAA receptor (bicuculline methiodide and
      picrotoxin). In control tissue, GABAB receptor antagonists P-(3-aminopropyl)-P
      diethoxymethyl-phosphinic acid (CGP 55845A), 3-N[1-(S)-(3,4-dichlorophenyl)
      ethyl]amino-2-(S)- hydroxypropyl-P-benzyl-phosphinic acid (CGP 35348), and 2
      hydroxysaclofen eliminated the late component of the biphasic IPSP but had no
      discernible effect on IPSPs evoked in post-SSLSE CA1 pyramidal cells. 3. A paired
      pulse paradigm was employed to investigate the integrity of presynaptic GABAB
      receptor-mediated inhibition of GABA release. To isolate pure GABAA-receptor
      mediated responses, and thus facilitate comparison with post-SSLSE tissue,
      control neurons were penetrated with intracellular electrodes containing
      Cs2SO4/lidocaine, N-ethyl bromide (QX-314), and IPSPs were evoked employing the
      monosynaptic IPSP protocol. In controls, paired pulses [interpulse intervals
      (IPIs) of 70-1,500 ms] resulted in a diminution of the second early, GABAA
      receptor-mediated chloride IPSP (IPSPA) relative to the first; maximum paired
      pulse depression (PPD) occurred at an IPI of 100 ms. GABAB receptor antagonists
      reduced PPD without affecting the amplitude of IPSPAs; the GABAB receptor agonist
      baclofen reduced the amplitude of both the first and second IPSPA and largely
      alleviated PPD. In contrast, no PPD was evident at any IPI in post-SSLSE neurons.
      Neither antagonists nor agonists of GABAB-receptor-mediated processes had an
      effect on either the degree of PPD or the amplitude of IPSPs. 4. To better
      approximate the pattern of CA1 pyramidal cell activation occurring during
      epileptiform activity. IPSPAs were evoked by trains of stimuli. In controls, mean
      monosynaptic IPSPA amplitude decreased by approximately 60% during a 3-Hz, 5-s
      train, with more than half the decline coming between the first and second IPSPs.
      In post-SSLSE, no significant IPSPA depression resulted from delivery of stimulus
      trains. Baclofen reduced the amplitude of control IPSPAs evoked during stimulus
      trains; both agonist and antagonists significantly lessened the degree of IPSP
      depression. These same agents altered neither IPSP amplitude nor the degree of
      use-dependent IPSP depression produced in post-SSLSE tissue during stimulus
      trains. 5. We conclude that a dysfunction of both presynaptic and postsynaptic
      GABAB-receptor-mediated processes occurs in hippocampal area CA1 in the post
      SSLSE model of TLE. GABAB receptor agonists and antagonists had no effect on post
      SSLSE CA1 pyramidal cell synaptic responses, whereas antagonists of the GABAA
      receptor completely eliminated IPSPs. Repetitive activation produced no use
      dependent synaptic depression. The implications of these findings for the
      epileptogenic potential of post-SSLSE CA1 and the "dormant basket cell"
      hypothesis are discussed.

PMID- 8871237
TI  - Basolateral amiloride-sensitive Na+ transport pathway in rat tongue epithelium.
AB  - 1. Experiments were conducted to test for the presence of basolateral Na+
      channels in the rat lingual epithelium. Researchers have proposed a model in
      which some lingual taste cells have Na+ channels in the basolateral membrane.
      That model is designed to account for the portion of the neural taste response
      and the portion of the transepithelial short-circuit current (Isc) in vitro that
      are insensitive to mucosal amiloride; some Na+ would diffuse across the tight
      junction into the cell via this lateral pathway, and would be transported out of
      the cell by Na+ pumps in the basal membrane. The model could also account for the
      differential effect of mucosal amiloride on Na+ salts of various anions, in which
      the neural taste responses to Na+ salts with anions larger than Cl- are more
      sensitive to mucosal amiloride than is the taste response to NaCl. 2. Voltage
      clamp data were obtained from an in vitro preparation of the anterior-dorsal rat
      tongue epithelium in which the connective tissue was removed by enzyme digestion.
      Isc in a modified Ussing chamber was reduced by amiloride in the submucosal
      solution. 3. The pattern of sensitivity to submucosal amiloride differed in
      several respects from the pattern for mucosal amiloride. The inhibition constant
      (Ki) was 52 microM amiloride concentration, higher than for the apical amiloride
      sensitive Na+ channel. The selectivity for Na+ over K+ was much less than for the
      response to mucosal amiloride; with 0.5 M NaCl or KCl on the mucosal side, the
      ratio of inhibition for the NaCl response to inhibition for the KCl response
      varied between 1 and 3. 4. As the concentration of NaCl in the mucosal solution
      was varied, submucosal amiloride caused little inhibition of Isc for mucosal NaCl
      below isosmotic concentration, with the percent inhibition increasing as mucosal
      salt concentration increased. With 0.5 M sodium gluconate in the mucosal
      solution, there was very little inhibition due to submucosal amiloride. 5. The
      results support the presence of amiloride-sensitive Na+ channels in the
      basolateral membranes of the dorsal tongue epithelium in rat, and are consistent
      with the proposed model in which these channels are present in taste cells.

PMID- 8871238
TI  - Nature and precision of temporal coding in visual cortex: a metric-space
      analysis.
AB  - 1. We recorded single-unit and multi-unit activity in response to transient
      presentation of texture and grating patterns at 25 sites within the parafoveal
      representation of V1, V2, and V3 of two awake monkeys trained to perform a
      fixation task. In grating experiments, stimuli varied in orientation, spatial
      frequency, or both. In texture experiments, stimuli varied in contrast, check
      size, texture type, or pairs of these attributes. 2. To examine the nature and
      precision of temporal coding, we compared individual responses elicited by each
      set of stimuli in terms of two families of metrics. One family of metrics,
      D(spike), was sensitive to the absolute spike time (following stimulus onset).
      The second family of metrics, D(interval), was sensitive to the pattern of
      interspike intervals. In each family, the metrics depend on a parameter q, which
      expresses the precision of temporal coding. For q = 0, both metrics collapse into
      the "spike count" metric D(Count), which is sensitive to the number of impulses
      but insensitive to their position in time. 3. Each of these metrics, with values
      of q ranging from 0 to 512/s, was used to calculate the distance between all
      pairs of spike trains within each dataset. The extent of stimulus-specific
      clustering manifest in these pairwise distances was quantified by an information
      measure. Chance clustering was estimated by applying the same procedure to
      synthetic data sets in which responses were assigned randomly to the input
      stimuli. 4. Of the 352 data sets, 170 showed evidence of tuning via the spike
      count (q = 0) metric, 294 showed evidence of tuning via the spike time metric,
      272 showed evidence of tuning via the spike interval metric to the stimulus
      attribute (contrast, check size, orientation, spatial frequency, or texture type)
      under study. Across the entire dataset, the information not attributable to
      chance clustering averaged 0.042 bits for the spike count metric, 0.171 bits for
      the optimal spike time metric, and 0.107 bits for the optimal spike interval
      metric. 5. The reciprocal of the optimal cost q serves as a measure of the
      temporal precision of temporal coding. In V1 and V2, with both metrics, temporal
      precision was highest for contrast (ca. 10-30 ms) and lowest for texture type
      (ca. 100 ms). This systematic dependence of q on stimulus attribute provides a
      possible mechanism for the simultaneous representation of multiple stimulus
      attributes in one spike train. 6. Our findings are inconsistent with Poisson
      models of spike trains. Synthetic data sets in which firing rate was governed by
      a time-dependent Poisson process matched to the observed poststimulus time
      histogram (PSTH) overestimated clustering induced by D(count) and, for low values
      of q, D(spike)[q] and D(intervals)[q]. Synthetic data sets constructed from a
      modified Poisson process, which preserved not only the PSTH but also spike count
      statistics accounted for the clustering induced by D(count) but underestimated
      the clustering induced by D(spike)[q] and D(interval)[q].

PMID- 8871239
TI  - Central and reflex neuronal responses elicited by odor in a terrestrial mollusk.
AB  - 1. We studied the responses to odor of a central olfactory processing organ and
      subsequent central outputs in the terrestrial mollusk Limax maximus. We used
      extracellular recording techniques and optical recording from preparations
      stained with a voltage-sensitive dye to characterize network responses in the
      central organ and whole nerve recording to characterize central odor-elicited
      outputs. 2. The central olfactory organ, the procerebral (PC) lobe, is a highly
      interconnected network of local olfactory interneurons that receives input from
      primary olfactory receptors. In the absence of odor the PC network is known to
      exhibit periodic waves of excitation and inhibition at a frequency of
      approximately 0.7 Hz. Here we study how different odor inputs affect the
      intrinsic oscillatory dynamics. 3. Odor stimulation causes the propagation of
      electrical activity along the lobe to transiently switch from the state with
      propagating waves, with typical phase shifts of one half cycle along the lobe, to
      a state with few or no phase differences along the lobe. The collapse of the
      phase gradient typically occurs without spatially localized changes in the
      amplitude of the oscillation, at least on the scale of our optical resolution,
      approximately 0.1 times the length of the lobe. In some trials, however, we
      resolved spatial nonuniformities in the magnitude of excitation across the lobe.
      4. The collapse of the phase gradient along the lobe in response to odor
      stimulation is robust on a trial-by-trial basis. Further, the change in phase
      gradient can occur with little or no change in the frequency of oscillation, as
      occasionally observed in response to weak odor stimulation. 5. Typically odor
      stimulation causes changes in the frequency of the oscillation. Two odors, one
      attractive (potato) and one repellent (amyl acetate), produced different patterns
      of change; potato induced a transient increase in frequency, whereas amyl acetate
      produced an initial decrease in frequency followed by a transient increase in
      frequency. We do not yet know whether these frequency change patterns are unique
      to these specific odors or to their behavioral meaning. 6. Previous work
      demonstrated direct connections from the PC lobe to the buccal and pedal ganglia,
      centers controlling feeding and locomotion, respectively. To establish a
      correlation between odor-induced changes in the PC lobe and activation of such
      centers and subsequently effector organs, we recorded from selected central
      connectives and peripheral nerve roots. The dependence of odor-elicited activity
      recorded in connectives and nerve roots on PC integrity was assessed by
      measurements of odor-elicited activity before and after PC ablation. 7. Odor
      stimulation caused activation of multiple units in the cerebrobuccal connective.
      One output of the buccal ganglion, the salivary nerve, also showed odor-elicited
      activation of an identified unit, the slow burster. The necessity of the PC lobe
      for activation of the slow burster was established by measurements of odor
      elicited activity before and after PC ablation. 8. Odor stimulation also caused
      activation of multiple units in the buccal mass retractor nerve. Activation of a
      fraction of these units (3 of 10) was dependent on an intact PC lobe, like the
      slow burster neuron in the salivary nerve. 9. Our results clearly show how
      stimuli may lead to changes in the spatial-temporal pattern of activity in a
      central circuit without changing the overall average level of activity in that
      circuit.

PMID- 8871240
TI  - Temporal resolution in olfaction II: time course of recovery from adaptation in
      lobster chemoreceptor cells.
AB  - 1. Adaptation and disadaptation rates determine the temporal response properties
      of sensory receptor cells. In chemoreception, temporal filter properties of
      receptor cells are poorly understood. We studied the time course of disadaptation
      in lobster antennular chemoreceptor cells by using in situ high-resolution
      stimulus measurement and extracellularly recorded spike responses. Fifteen
      receptor cells were each tested with two series (one at 10 microM, one at 100
      microM) of three odor (hydroxyproline) pulses: a 200-ms test pulse, a 5-s
      adapting pulse, and a 200-ms probe pulse after time intervals ranging from 1 to
      60 s. After complete adaptation by the adapting pulse, individual cells recovered
      at different rates. After 1 s, a third of the cells responded with a mean
      response of 3 spikes/cell, representing approximately 20% recovery. All cells
      fully recovered between 10 and 30 s. Mean full recovery was within 25 s, with a
      time constant of 14 s, independent of stimulus concentration.

PMID- 8871241
TI  - Multiple mechanisms for peripheral activation of the peptide-containing radula
      mechanoafferent neurons B21 and B22 of Aplysia.
AB  - 1. Recently a cluster of sensory neurons (peptidergic radula mechanoafferents)
      has been identified in the buccal ganglion of Aplysia that is likely to play an
      important role in influencing the activity of feeding motor programs. All of the
      neurons of this cluster, which includes the identified cells B21 and B22, send
      axons via the radula nerve to a layer of tissue that lies under the chitinous
      radula (the subradula tissue). 2. We show that the subradula tissue has
      contractile properties. In the absence of the CNS, contractions of the subradula
      tissue are elicited if the subradula tissue is stretched. Alternatively,
      contractions are elicited when extracellular suction electrodes are used to
      stimulate buccal nerve 3 or the radula nerve. 3. Previous studies have shown that
      neurons of the B21/B22 cluster respond to peripherally applied mechanical
      stimuli. We show that these neurons are also activated when the subradula tissue
      contracts. Axon spikes (A spikes) can be intracellularly recorded from radula
      mechanoafferent neurons when contractions of the subradula tissue are elicited
      either by stretch or by extracellular stimulation of buccal nerve 3. 4.
      Mechanical stimuli that are subthreshold when applied alone elicit A spikes if
      they are applied while the subradula tissue is contracting. We postulate that
      this type of interaction may play an important role in gating sensory input to
      the feeding central pattern generator.

PMID- 8871242
TI  - Neuronal activity in posterior parietal area 7a during the delay periods of a
      spatial memory task.
AB  - 1. Neuronal activity was recorded from area 7a of monkeys performing a delayed
      match-to-sample task requiring release of a behavioral key when a visual stimulus
      appeared at a remembered spatial location. 2. Activity in the delay periods was
      significantly elevated in 28% of 405 neurons studied and could be classified as
      either sustained or anticipatory in nature. 3. Sustained activity was
      characterized by maintained or slowly decreasing discharge rates that were
      typically greater when the preceding stimulus was at a location that evoked a
      strong response. Sustained activity was terminated when a subsequent stimulus
      appeared at another location. 4. Anticipatory activity was characterized by
      accelerating discharge rates that were ordinarily greater after a stimulus at a
      location that evoked a weak response. Anticipatory activity was often associated
      with facilitated responses to the next stimulus. 5. These data demonstrate that a
      population of neurons in area 7a is active during the delay periods of a spatial
      memory task that does not require a behavioral response directed toward the
      location of the stimulus. This activity could represent a short-term memory trace
      for the spatial location of the preceding stimulus.

PMID- 8871243
TI  - Latency: another potential code for feature binding in striate cortex.
AB  - 1. We recorded the responses of 37 striate cortical complex cells in fixating
      monkeys while presenting a set of oriented stimuli that varied in contrast. 2.
      The two response parameters of strength and latency can be interpreted as a code:
      the strength defines the stimulus form (here the orientation), and the latency is
      more a function of the stimulus contrast. 3. Synchronization based on latency
      could make a strong contribution to the process of organizing the neural
      responses to different objects, i.e., binding.

PMID- 8871244
TI  - Anticipatory saccades in sequential procedural learning in monkeys.
AB  - 1. In a preceding paper we examined the short-term and long-term processes of
      learning of sequential procedures in monkeys. We now report that the pattern of
      eye movements changed along with the long-term learning. 2. The monkey's task was
      to press five consecutive pairs of target buttons (indicated by illumination) in
      the correct order for every pair, which the monkey had to find by trial and error
      (2 x 5 task). The whole sequence was called the "hyperset"; each pair was called
      the "set." 3. Initially, the saccade toward the correct target occurred after
      illumination of the targets (visually guided saccade). After sufficient learning,
      the saccade tended to occur before the target illumination (anticipatory
      saccade). This was true only for the hyperset that had been learned. 4. The
      likelihood of anticipatory saccade increased gradually over 20-30 days of
      practice of the particular hyperset. The time course was similar to how the hand
      learned (button press latency). 5. The monkeys were required to use the same hand
      for each hyperset throughout learning, except when we asked them to use the
      opposite hand. The nearly perfect performance due to the extensive practice was
      then deteriorated by the use of the opposite hand. We found, in addition, that
      anticipatory saccades became much less frequent. This finding suggests that
      critical for the skilled performance was the combination of the eyes and the side
      of the hand that was used for the practice of a given sequence.

PMID- 8871245
TI  - Intestinal endotoxins as co-factors of liver injury in obstructive jaundice.
AB  - The concept of endotoxin-mediated rather than direct liver injury in biliary
      obstruction was investigated using the experimental rat model of bile duct
      ligation (BDL) and small bowel bacterial overgrowth (SBBO). Small identical doses
      of intravenous endotoxin (bacterial LPS) caused a significantly more severe liver
      injury in rats with BDL, compared with sham-operated rats, suggesting the
      possible contribution of LPS in this type of liver damage. BDL was then combined
      with surgically created jejunal self-filling blind loops, which resulted in SBBO.
      Plasma LPS level increased significantly, and once again a more severe liver
      injury, determined by liver histology and serum gamma-glutamyl transpeptidase
      levels, was observed compared with the control group of rats with BDL+self
      emptying blind loops. The data presented suggest that small amounts of exogenous
      LPS and/or the ordinarily innocous amounts of LPS constantly absorbed from the
      intestinal tract may be critical in the hepatic damage caused by obstruction of
      the biliary tract.

PMID- 8871246
TI  - Laparoscopic versus open cholecystectomy: a prospective matched-cohort study.
AB  - To compare the results of laparoscopic cholecystectomy (LC) and open
      cholecystectomy (OC) for symptomatic cholelithiasis in elective surgery we
      performed a prospective matched-cohort study. Hundred consecutive patients who
      underwent LC in the period Sept. 1990-June 1992, and 100 patients who were age
      and sex matched and underwent an elective OC in the foregoing two years (1989
      1990) were studied. The median operation time for LC (75, 40-180 min) was
      significantly longer than for OC (55, 20-155 min; p <0.001). Postoperative
      hospitalization was significantly shorter after LC (3, 1-16 days), compared with
      OC (7, 4-22 days; p <0.001). Conversion of LC to OC occurred in 12 (12%) patients
      initially scheduled to undergo LC. Complications occurred in 5 patients (5%)
      after LC and in 5 patients (5%) after OC. The calculated expenses (operation and
      postoperative hospitalization, 3rd class) were approximately fl. 3740,- for LC
      (excl. investments for pieces of apparatus) and fl. 6725,- for OC. This study
      demonstrates that LC can be performed safely with the number of complications
      comparable to those for OC. Bile duct injury is a serious potential threat. The
      main advantages of LC are the minimal trauma, with more rapid recovery. Insurers
      seem to benefit from reduced postoperative disability and earlier discharge.

PMID- 8871247
TI  - Glucagonoma associated with calculous pancreatitis.
AB  - A Patient with a glucagonoma associated with calculous pancreatitis is reported.
      The authors know of only one other such patient. Because the calculous
      pancreatitis developed both upstream and downstream from the tumor, it cannot be
      attributed to obstruction of the pancreatic duct by the tumor. Continued critical
      appraisal is needed to determine whether the association of the glucagonoma and
      pancreatitis is etiologically related or merely coincidental.

PMID- 8871248
TI  - Hepatobiliary cystadenomas and cystadenocarcinoma. Report of five cases.
AB  - Clinicopathologic correlation of five cases of cystadenomas of the liver are
      reported. All patients were female and radical surgical procedure, total excision
      or resection was performed four times, and partial excision once. In all patients
      the postoperative course was uneventful and they are all alive and well. Examined
      by conventional histological and special immuno-histochemical stains the tumors
      fulfilled diagnostic criteria for these rare cystic growths. The cyst wall was
      composed of three, histologically distinct layers. From the viewpoint of
      histogenesis and differential diagnosis immunohistochemical properties were
      analysed. CEA and EMA were demonstrated in epithelial cells and Vimentin in
      stromal cells.

PMID- 8871249
TI  - The potential role of intraoperative ultrasonography in the surgical treatment of
      hilar cholangiocarcinoma.
AB  - The role of intraoperative ultrasonography (IOU) in the surgical treatment of
      hilar cholangiocarcinoma was explored in twenty-two patients, 17 males and 5
      females. The mean age was 55 years (range 36-78 years). Preoperative imaging
      studies included abdominal ultra-sonography and/or CT scan, and visceral
      angiography. Operations performed were segment III bypass in 18 patients, local
      resection of tumour in 2 and resection of tumour en bloc with left hepatectomy in
      2. Interpretation of IOU in terms of vascular involvement by the tumour (as
      compared to angiography or operative findings) was correct in 21 patients; no
      vascular invasion in 20 and portal vein invasion in the remainder. One false
      negative result occurred in a patient whose IOU failed to show right hepatic
      artery encasement by the tumour. When compared to postoperative cholangiography
      or surgical specimen, IOU correctly demonstrated location and extent of the
      tumours in all but one patient who had incomplete tumour resection. IOU was also
      helpful in locating segment III duct for biliary bypass. The mean time used for
      IOU was 15.1 min (range 10-20 min.), and there was no procedure-related
      complication. When supplemented with operative exploration, IOU seems to be very
      useful in the assessment of the resectability of hilar cholangiocarcinoma.

PMID- 8871250
TI  - Surgicel reinforced resection lines in left-sided hepatectomy with linear
      stapling device. An experimental study on pigs.
AB  - Fourteen pigs underwent left-sided hepatectomy. The resection was performed with
      a linear stapling device and the pigs were randomised to either Surgicel
      reinforced resection lines or not. The median time required for resection was 25
      min (range 17-30) in the Surgicel reinforced group compared to 30 min (range 21
      41) in the stapled group. This difference was, however, not statistically
      significant (p = 0.053). The postoperative haemoglobin value was lower in the
      stapled group compared to the Surgicel reinforced group 69 g/l (range 42-85)
      versus 82 g/l (range 78-90) (p = 0.018). The estimated blood losses by weighing
      the compresses were 287 ml (range 166-379) for the stapled group and 204 ml
      (range 152-264) for the Surgicel reinforced group (p = 0.053). The median number
      of additional haemostatic sutures in the Surgicel reinforced group was 7 (range 3
      11) and in the stapled group 10 (range 5-15) (p = 0.038). The haemoglobin value
      was similar in the two groups 1 week postoperatively; 100 g/l (range 87-104) and
      102 g/l (range 95-114), p = 0.27, in the stapled group and the Surgicel
      reinforced group, respectively. In the stapled group reinforced with the Surgicel
      there was one postoperative death. In the solely stapled group there was no
      postoperative death (p = 0.5). Four out of six pigs in the Surgicel group had
      massive adhesions to the resection lines. One of these six pigs was sacrificed
      postoperatively as it was ill and had small bowel obstruction secondary to
      Surgicel induced adhesions. On the other hand, no adhesions were seen in the
      solely stapled pigs (p = 0.09). At this point, we can not recommend the use of
      Surgicel to reinforce resection lines at stapled liver resection in the clinical
      situation, because of the high frequency of adhesions this material creates.

PMID- 8871251
TI  - Primary extrahepatic bile duct carcinoids.
AB  - Biliary tact carcinoids are extremely rare: only ten cases have been reported up
      to now. The Authors describe a successfully treated carcinoid tumour of the
      proximal bile duct and review the literature about these rare malignancies.
      Despite extensive preoperative work-up, including ultrasound, CT scan and ERCP, a
      definite diagnosis is hardly possible prior to histologic examination of the
      operative or necropsy specimen. Due to the slow-growing nature and the non
      aggressive behaviour of these malignancies, surgical resection followed by
      biliodigestive anastomosis should be the treatment of choice.

PMID- 8871252
TI  - Duodenum-preserving resection of the head of the pancreas: the significance as a
      diagnostic therapy of the lesion in the pancreatic head.
AB  - A 75-year-old man who was diagnosed as having mucin-producing pancreatic cystic
      lesion of the main pancreatic duct by duodenoscopic examination was reported.
      Because of the low malignant potential of such lesions, duodenum-preserving
      resection of the head of the pancreas was performed, and the intra-operative
      histological examination showed no malignancy of the resected pancreatic head and
      no other surgical procedures, such as lymph-adenectomy nor pancreato-duodenectomy
      were necessary. The significance of this case report lies in that a less invasive
      operation should be selected at first to diagnose whether the lesion is malignant
      or not, and also that the selected operation itself must be sufficient to resect
      an adequate part of the pancreatic tissue involving the cystic lesion, if not
      malignant. Here, we report the process to select the procedure and the surgical
      technique.

PMID- 8871253
TI  - Liver transplantation: does prolonged storage promote non-anastomatic biliary
      strictures [correction of structures] ?

PMID- 8871254
TI  - Resection margins for colorectal metastases to the liver: do they make a
      difference?

PMID- 8871255
TI  - Hepatic cryotherapy for cancer: a review and critique.

PMID- 8871256
TI  - [Perineal injuries in complicated pelvic trauma].
AB  - Severe comminuted pelvic ring fractures are often associated by genitourinary and
      rectal injuries. Because of severe retroperitoneal bleeding, shock management has
      to be initiated before further diagnosis of the perineal lesions. If normotonic
      conditions cannot be achieved by volume replacement, a pelvic clamp is indicated
      providing immediate reduction of the posterior pelvic ring. A subsequent
      emergency laparotomy has to be considered if stable circulatory conditions cannot
      be achieved by these emergency procedures. After the initial management of the
      hypovolemic shock further examination of the rectum by endoscopy and
      endosonography is performed. Urethral lesions have to be excluded by ultrasound
      of the bladder, retrograde urethrography and intravenous urography. Urethral and
      bladder injuries can be initially treated by suprapubic fistula, whereas rectal
      and pararectal wounds have to be managed by immediate debridement, jet-lavage and
      wound drainage. Rectal wall and sphincter lacerations are initially restored by
      suture because delayed reconstructions have poor results. A deviation colostomy
      is mandatory in cases of colonic and rectal injuries about the internal
      sphincter.

PMID- 8871257
TI  - [Ano-genital injuries in female victims of sexual assault].
AB  - Sexual assault continues to represent the most rapidly growing violent crime in
      the USA. Statistics prove a persistent rise in rape incidence with poor
      conviction rates. This knowledge, along with the vast multitude of emotional
      sequilae of rape and self-perceived inferior legal status of the involved females
      results in a high percentage of unreported cases. This presented paper reports of
      ano-genital trauma in case of sexual assault. Under 2970 victims of sexual
      assault, examined and treated between 1967-1985 in the Department of Gynecology
      and Obstetrics Charlottenburg (Free University of Berlin), a percentage of almost
      40% was represented by children in the age of 0-14. Therefore, only 1696 patients
      with complete gynecological examination with correct case history examination for
      injuries and traces of sperm, infections could be presented. The total rate of
      injuries was: Perineum 8.4%, vulva 5.4%, vagina 1.8%, pelvis/thighs 14.2%. The
      highest risk to be injured in case of sexual assault had the age group of victims
      over 55 years (nearly 50%). The lowest rate of injury has been encountered in the
      age groups 0-5 years, 6-10 years, 26-35 years: Under 10%. A solitary anal-injury
      has not been found. Specific training in emergent and chronic care for the
      victims, both physical and mental, in conjunction with preventive measures to
      genital infections and pregnancy, are necessary when the gynecologist is
      involved.

PMID- 8871258
TI  - [Etiology, pathogenesis and classification of anal fissure].
AB  - Anal fissure is one of the most common causes of anal pain but its etiology and
      pathophysiology remain obscure. Many theories have been advanced to explain the
      origin of anal fissures but trauma of faecal mass and hypertonicity of the
      internal sphincter seem to be the most important factors. The initial lesion in
      anal fissure is a tear in the anoderm mostly in its posterior midline caused by
      overstretching of the anal canal. Secondary fissures may occur on a commonly
      lateral position as a result of inflammatory bowel disease, previous anal
      surgery, venereal, dermatologic, infectious or neoplastic disease. As the fissure
      becomes deeper and more chronic the sclerotic fibres of the internal anal
      sphincter are seen as well as a sentinel pile and a hypertrophied anal papilla.
      The disease enters in a vicious circle of anal pain, constipation, faecal trauma
      and sphincter spasm.

PMID- 8871259
TI  - [Anal fissure: conservative treatment].
AB  - Anal fissure is a common and painful disorder. Conservative treatment must be
      reserved for acute forms. Hygiene rules, stool softeners and topical local
      anaesthetic agents are the mainstays of treatment. Healing often takes long time.
      Recurrences can be prevented with chronical prescription of stool softeners.
      Surgical treatment is indicated for chronic fissures, acute fissures refractory
      to 2 monthes conservative treatment and persistent painful forms.

PMID- 8871260
TI  - [The surgical treatment of anal fissure].
AB  - 60 patients with relapsing acute or chronic anal fissure underwent lateral
      internal sphincterotomy between July 1987 and July 1994. 53 of them have been
      followed up. The results of this treatment are excellent and are in accordance to
      those of other series. This technique is proposed as a method of choice in the
      treatment of anal fissure.

PMID- 8871261
TI  - [Surgical therapy of anal fissure].
AB  - Lateral internal sphincterotomy has shown to be a very efficient method to treat
      acute and especially chronic anal fissure. The question remains, whether it is
      possible to optimate the short and long term outcome by individualizing the
      extent of sphincterotomy. This can be done by calculating the length of the anal
      canal and the area under the curve on a preoperative manometric pressure profile.
      We present the short and long term results over 3 years in a consecutive series
      of 30 anal fissures. All patients remained symptomfree and had full anal
      sphincter competence.

PMID- 8871262
TI  - Cellular activation products in osteoarthritis synovial fluid.
AB  - In order to address the issue of the role of mast cells (MC) and nitric oxide
      (NO) in rheumatic synovial-fluid diseases, synovial fluid (SF) collected from the
      knee of patients with osteoarthritis (OA), articular chondrocalcinosis (ACC) or
      rheumatoid arthritis (RA) was examined for the levels of mast cells (MC),
      histamine, tryptase, phospholipase A2 and nitrite. MC counts were found to be
      elevated in the SF of OA patients as compared with RA patients. Histamine content
      in SF parallelled the number of MC. Tryptase levels were elevated in OA in
      comparison to RA and ACC, but the difference was not statistically significant.
      Identical PLA2 levels were recorded among the 3 groups. Nitrite concentrations
      were also higher in SF from OA patients as compared to RA patients. These results
      suggest that mast cells (MC), in association with various inflammatory cells, may
      contribute to inflammation and cartilage breakdown in osteoarthritis (OA).

PMID- 8871263
TI  - Changes of some immune functions after percutaneous transluminal coronary
      angioplasty (PTCA).
AB  - This study aimed to evaluate some aspects of the immune response in 10
      cardiopathic patients during the execution of percutaneous transluminal coronary
      angioplasty (PTCA) by obtaining blood samples from coronary sinus. In particular
      we considered some PMN functions as well as lysosomal release and oxidative
      metabolism evaluated as chemiluminescence and superoxide anion (O2) production.
      We also studied serum levels of complement C3 and C4, lymphocyte populations
      (CD3, CD4, CD8, CD19, CD16) and plasmatic determinations of interleukin 2 (IL2).
      After PTCA, we found a decrease of total count of blood lymphocytes, whereas the
      number of neutrophils remained unchanged. The decrease involved to a similar
      extent the lymphocyte subsets CD3, CD4 and CD8, whereas CD19 and CD16 were
      unchanged. The plasmatic levels of IL2 did not show any significant modification.
      Concerning PMN, their chemiluminescence was significantly increased after PTCA as
      compared to basal values: this response was promptly detectable in isolated PMN,
      both without and with stimulation with fMLP. Similarly superoxide anion
      production, both spontaneous and stimulated, was increased in PMN suspensions
      after PTCA, even if this increase did not reach statistical significance. As
      regards circulating levels of lysosomal enzymes, we found a significant increase
      of plasmatic levels of elastase, whereas the serum determinations of lysozyme and
      betaglucuronidase did not change. Concerning the complement system, we found a
      significant decrease of complement fractions C3 and C4. In conclusion, our
      results showed certain changes in some humoral and cellular systems; in
      particular the neutrophil activation through the release of proteolytic enzymes
      and the generation of oxygen radicals could increase the damage to vessel walls
      and activate other systems having a negative effect in the ischaemia-associated
      consequences.

PMID- 8871264
TI  - Tolerability of mofebutazone in asthmatic patients.
AB  - Twenty-seven human volunteer asthmatic patients were each given one tablet of
      mofebutazone (300 mg) twice daily for 15 days. Pulmonary ventilatory function
      test (forced expiratory volume test) as well as bronchoalveolar lavage (BAL) were
      performed one day before initiation of treatment and one day after completion of
      the course; in the BAL, prostaglandin E2 (PGE2), prostaglandin F2alpha
      (PGF2alpha) and leukotrienes (LTs) were also estimated. It was found that there
      was no increase in the incidence or severity of the asthmatic attacks during the
      course of mofebutazone treatment. The drug tended to improve the tested pulmonary
      ventilatory functions or at least to leave them unchanged. All the mofebutazone
      treated individuals showed a dramatic reduction in the concentrations of PGE2,
      PGF2alpha and LTs in their BAL, but there was no consistent correlation between
      the extent of reduction and the degree of benefit or worsening sustained by any
      individual patient. It is evident from the present study that mofebutazone has
      shown good tolerability which was associated with an improvement in the pulmonary
      ventilatory functions, a fact that would seem to advocate the use of this non
      steroidal antiinflammatory drug (NSAID) in asthmatic patients whenever a need for
      such therapy becomes necessary.

PMID- 8871265
TI  - Effect of bezafibrate on HDL with APO A-I and APO A-II and on HDL with APO A-I
      without APO A-II in hyperlipidaemic patients.
AB  - On the basis of apoprotein composition, high-density lipoprotein (HDL) particles
      may be subdivided into two main subpopulations defined by the presence in the
      lipoprotein molecule of apo A-I (Lp A-I) and of both apo A-I and apo A-II (Lp A
      I:A-II). The effect of slow-release bezafibrate 400 mg a day on Lp A-I and Lp A
      I: A-II was evaluated in 34 hyperlipidaemic patients (19 with
      hypercholesterolaemia and 15 with hypertriglyceridaemia). Seventeen patients on
      low-fat low-cholesterol diet only were taken as the reference group. In the
      reference group, no change in HDL-C, apo A-I, apo A-II, Lp A-I and Lp A-I:A-II
      occurred during the 3 months of observation. In patients on bezafibrate, HDL-C,
      apo A-I and apo A-II significantly increased. Lp A-I:A-II increased by 33% in
      hypercholesterolaemic and by 29% in hypertriglyceridaemic patients. Lp A-I
      decreased by 15% in hypercholesterolaemic patients and did not change
      significantly in hypertriglyceridaemic patients. This differential effect of
      bezafibrate on apo-A-defined HDL subpopulations in hypertriglyceridaemia and in
      hypercholesterolaemia is in accord with previous studies on the effect of the
      drug on HDL subfractions defined by their density.

PMID- 8871266
TI  - A two-year study on the efficacy and tolerability of policosanol in patients with
      type II hyperlipoproteinaemia.
AB  - This is a report of the results of a two years' randomized, double-blind placebo
      controlled study of the efficacy, safety, and tolerability of policosanol
      administered at 5 mg twice-a-day in the treatment of type II
      hyperlipoproteinaemia. The study included 69 patients from both sexes, in whom
      total cholesterol and low-density-lipoprotein cholesterol (LDL-C) were not
      controlled sufficiently by diet. The treatment effect on total cholesterol and
      LDL-C was maintained during the 2-year follow up. Thus, percent reductions 24
      months after therapy were 25% (LDL-C) and 18% (cholesterol). All comparisons with
      placebo were significant. Similarly, ratios of LDL-C to HDL-C and cholesterol to
      HDL-C were significantly reduced and such decreases were maintained during the
      study. Policosanol raised significantly the values of high-density lipoprotein
      cholesterol (HDL-C) during the study and maximal increases were reached 12 months
      after therapy (+21%). From this time the increases mildly declined to +14% and
      +11.2% respectively at 18 and 24 months after therapy. No significant changes in
      triglycerides were observed as compared with baseline or placebo. No patient
      withdrew from the study because of adverse effects. No drug-related clinical or
      biochemical adverse side-effects were observed. Any adverse experiences reported
      were mild and transient; moreover, no significant differences were obtained when
      compared with those reported by the placebo group. The results indicate that
      policosanol administered for two years to patients with type II
      hypercholesterolaemia shows a maintained efficacy as well as very good safety and
      tolerability.

PMID- 8871267
TI  - [Ophthalmology for the practitioner and modern ocular surgery].

PMID- 8871268
TI  - [Classification and differential diagnosis of uveitis].

PMID- 8871269
TI  - [Ocular lesions due to diabetes].

PMID- 8871270
TI  - [Neuro-ophthalmological complications of Horton's disease].

PMID- 8871271
TI  - [Current cataract surgery].

PMID- 8871272
TI  - [Retinal venous occlusion].

PMID- 8871273
TI  - [Refractive surgery: techniques and application at the Corneal and Refractive
      Surgical Center Jules Gonin in Lausanne].

PMID- 8871274
TI  - [Principal vitreo-retinal disorders treated with vitrectomy].

PMID- 8871275
TI  - [Glaucoma and risk factors. Comparative study of cardiovascular risk factors in
      primary open-angle glaucoma, normal-pressure glaucoma and simple ocular
      hypertension].
AB  - This study compares the cardiovascular disease and risks factors, as well as
      ophthalmic findings of 20 primary open angle glaucoma, 23 low tension glaucoma
      and 11 ocular hypertensive patients. The low tension glaucoma group presents a
      high incidence of cardiovascular disease and risk factors, while the primary open
      angle glaucoma and the ocular hypertensive patients, present respectively, an
      average and low incidence of cardiovascular disease and risk factors.

PMID- 8871276
TI  - [The eye and AIDS: ophthalmological consultation for AIDS screening, 1-year
      retrospective study].

PMID- 8871277
TI  - [Proximal femoral fractures: fixation and nailing. Role of an implant fixed with
      a femoral head screw and nailing of the femoral diaphysis in per- and
      subtrochanteric fractures--results in a consecutive series of 28 Gamma long
      nails].

PMID- 8871278
TI  - [Controversy].

PMID- 8871279
TI  - [Working through the Nazi past by the German psychoanalytic community. Attempt at
      an assessment from close distance].
AB  - Taking both a personal and a general perspective, the author sketches the socio
      historical circumstances leading to the destruction of psychoanalysis in Germany
      between 1933 and 1945. In so doing he looks at the attitudes and responses
      evinced by those "Aryan" analysts who believed it to be possible to "rescue"
      psychoanalysis from Hitler's grasp without forfeiting any of its central
      convictions. Then Wangh takes Alexander and Margarete Mitscherlich's pioneering
      work. The Inability to Mourn as a starting-point for a reconstruction of the
      revolt staged in the late seventies and early eighties by the younger generation
      against their analytic parents and their continuing silence about the past--a
      revolt that took place not least in the pages of this journal. Central to his
      remarks is a concern with the working-out of persistent feelings of shame and
      guilt and success (or failure) in the attempt to overcome and/or integrate them.
      Finally the author advances a suggestion as to how the emotional--and verbal-
      barriers between the descendants of the victims and those of the perpetrators
      could be removed.

PMID- 8871280
TI  - [Sigmund Freud and Hans Bluher in up to now unpublished letters].
AB  - In the years 1912 and 1913 there occured an epistolary encounter between the
      founder-father of psychoanalysis and the young Hans Bluher who had been active in
      the Wandervogel movement, a German youth movement with strong traditionalist and
      nationalist leanings. Their correspondence centered around the evaluation of male
      homosexuality, a point on which Freud and Bluher were not in entire agreement. In
      his introduction Neubauer outlines the intellectual nub of this debate and
      sketches Bluher's later career and his gradual transformation into a
      biologistically motivated anti-Semite completely and utterly disowned by Freud.

PMID- 8871281
TI  - Analysis of cellular proteins in achondroplasia by two-dimensional
      electrophoresis.
AB  - An abnormal protein pattern was found in cultured fibroblasts from three of seven
      patients with achondroplasia. All three patients showed two abnormal protein
      spots which were not detected in any of the normal and pathological cell strains
      examined in this study. Clinical manifestations of these three cases were
      compared with those of other cases, but no differences were identified between
      them from the data available at present. The significance of these protein spots
      were discussed.

PMID- 8871282
TI  - The ultrastructural study on epithelium of gallbladder with gallstones.
AB  - To investigate the fine structures of epithelium, 30 patients bearing gallstones
      were subjects for this study: ten for gallbladders with cholesterol stones, 10
      for pigment stones and 10 for the control. The electron microscopic examination
      of these specimens revealed that all the epithelial cells from three gallbladder
      models had similar ultrastructural features. The most striking feature was the
      presence of numerous mucous droplets in the apical portion of the all epithelial
      cells. Another prominent finding was multivesicular bodies predominantly in
      gallbladders with pigment stone. Golgi apparatus, rough endoplasmic reticulum and
      mitochondria were apparent and well-developed. Crescent and semi-circular
      structures were found exclusively in gallbladders with cholesterol gallstones.
      According to the well-developed Golgi apparatus, rough endoplasmic reticulum and
      abundant mucous droplets, these epithelial cells are presumably mucus secretory
      cells. The gallbladder epithelium may play an important role in regulating the
      stone formation.

PMID- 8871283
TI  - Evaluation of alveolar integrity in patients with non-insulin dependent diabetes
      mellitus using Tc-99m DTPA and HMPAO radioaerosol inhalation lung scintigraphies.
AB  - The alveolar integrity (AI) in 17 patients of non-insulin dependent diabetes
      mellitus (NIDDM) who had normal findings in the chest x-ray and pulmonary
      function test was measured by Tc-99m DTPA and HMPAO radioaerosol inhalation lung
      scintigraphies (DTPA and HMPAO). The degree of AI damage in NIDDM was presented
      as the slopes (%/min) of the time-activity curves from the dynamic of both lung
      imagings using DTPA and HMPAO. The AI of NIDDM patients was compared with the AI
      of 23 normal controls. The results show that (1) the slopes of DTPA were larger
      than those of HMPAO in any portion of either of the lungs for both of the study
      groups, and that (2) the slopes of DTPA and HMPAO were larger in NIDDM than those
      in normal controls over any portion of the lungs. The results suggest that (1) at
      least two different clearance mechanisms for aerosol particles in the lungs are
      at work; and (2) the AI damage in NIDDM developed in both the hydrophilic and
      lipophilic parts of the alveoli. In conclusion, the AI damage which appeared as
      larger slopes of DTPA/HMPAO in our study may be early findings of lung
      complications in NIDDM patients, which are different from the traditional studies
      such as chest x-ray or pulmonary function test.

PMID- 8871284
TI  - The effect of "chi-han (hot nature)" Chinese herbs on the secretion of IL-1 beta
      and TNF-alpha by mononuclear cells.
AB  - The effect of "chi-han (hot nature)" Chinese herbs on the secretion of the
      cytokines IL-1 beta and TNF-alpha was investigated by studying the in vitro
      effect of the "hot nature" Chinese herbs Radix aconiti, Evodia rutaecarpa,
      Zingiberis rhizoma, and Cortex cinnamomi. An ethanolic extract of each of these
      Chinese medicinal herbs was added to human peripheral mononuclear cell culture
      medium and allowed to react for various specified lengths of time. The culture
      medium supernatants were collected and tested for their cytokine levels at
      specified time intervals. We found different reaction patterns of cytokine
      secretion among these "hot nature" Chinese herbs. Radix aconiti extract showed an
      augmentative effect on the secretion of cytokines IL-1 beta and TNF-alpha with
      20% to 50% concentrations of the pure herbal extract, especially when the
      reaction time was 18 or 24 hours. Evodia rutaecarpa extract showed a biphasic
      effect on the secretion of IL-1 beta and TNF-alpha when the reaction time was 18
      or 24 hours. The secretion of cytokines was stimulated by low concentrations of
      the herbal extract, but inhibited by higher concentrations of the extract.
      Zingiberis rhizoma extract also showed a biphasic effect on the secretion of
      cytokine IL-1 beta when the reaction time was 18 or 24 hours. As for Cortex
      cinnamomi extract, no significant augmentative effect on cytokine secretion was
      found in our study. In consideration of the pyrogenic property of cytokines, it
      would appear that "hot nature" Chinese herbs can be further divided into
      different subgroups with minute differences based on their different effects on
      cytokine secretion.

PMID- 8871285
TI  - The effect of ultrasonic scaling therapy in periodontitis III. A longitudinal
      study over three years.
AB  - The purpose of the present study was to examine and evaluate the effect of
      clinical trials of non-surgical periodontal therapy (NSPT) by ultrasonic scaling
      alone for three years. A total of 51 individuals (27 males; 24 females) ranging
      in age from 21 to 61 years with moderately to extremely advanced periodontitis
      were studied following baseline assessments which included gingival index, plaque
      index, probing pocket depths, and probing attachment levels (PALs). The patients
      were subjected to NSPT by using supra- and subgingival scaling with ultrasonic
      instrumentation alone. The results showed that this therapy resulted in a
      pronounced and significant reduction (p < 0.001) of gingival inflammation and
      dental plaque formation for the 3 years of study. In addition, a significant
      reduction of probing depth as well as an obvious gain of PALs were found greater
      in sites with initial depth of 4-6 mm and 7 mm or more (p < 0.001) than those in
      sites with initial probings of 1-3 mm (p > 0.05) at each survey time point.

PMID- 8871286
TI  - Zigzag V-Y advancement flap for medial canthal defect after tumor excision.
AB  - A zigzag V-Y advancement flap based on the angular artery is used to repair the
      medial canthal defect after tumor excision. Only the middle-third subcutaneous
      attachments to the flap are left intact, which contain the vascular pedicle. The
      advancing zigzag edges of the flap can be naturally inserted around both limbs of
      the medial canthus, and this disperses the tendency to linear contracture and
      "trap-door" scarring. The described technique is an excellent choice for medial
      canthal defect, providing a well-contoured and aesthetically pleasing
      reconstruction.

PMID- 8871287
TI  - Mechanical property analysis of small bone fixators.
AB  - The purpose of this study is to establish a database and to compare mechanical
      properties between various types of small bone fixators. Hollow maple dowels are
      uniformly produced to simulate small bones in this study. Furthermore, transverse
      osteotomy, transverse osteotomy with 2 mm gap, and 45 degrees oblique osteotomies
      are created to simulate stable, unstable, and spiral fractures. Each fracture
      pattern is then approximated with four types of fixators: (1) Aesculap mini
      external fixator, (2) mini A-O plate and screw, (3) cross pin, and (4) self
      assembled mini external fixator. Finally, tension, torsion, and bending tests are
      performed with INSTRON. In three different fracture patterns, dorsal plating has
      the strongest tensile rigidity and lateral bending rigidity. In stable and
      unstable fractures, Aesculap mini external fixator has the strongest torsional
      rigidity. However, mini A-O plate has the strongest torsional rigidity in 45
      degrees oblique fractures. In stable fractures, dorsal plating, lateral plating,
      and mini external fixator all have good anterior bending rigidity without
      significant differences. Nevertheless, only lateral plating and mini external
      fixator show good anterior bending rigidity in unstable and 45 degrees oblique
      fractures. Except in torsional rigidity, Aesculap mini external fixator is not
      significantly stiffer than the self-assembled external fixator. As expected,
      cross pin is the weakest fixator. Differences in mechanical stiffiness between
      the four types of small bone fixators are provided in this study. Additionally,
      one should also consider the indication when choosing a proper fixator.
      Complication rate can then be lowered to achieve successful surgery in treating
      small bone fractures.

PMID- 8871289
TI  - [Paranasal sinuses, middle ear, and allergy].

PMID- 8871288
TI  - Caregiving experiences of family caregivers of elderly persons with dementia in
      northern Taiwan.
AB  - This is part of the follow-up to of a large epidemiological study on the
      prevalence of dementia. Twenty-nine caregivers of demented elderly persons
      identified from previous study were further studied in the second phase in order
      to understand the caregiving experiences. In home, one-time, face-to-face
      interviews were used to collect data. Qualitative data derived from open-ended
      questions were transcribed verbatim and the content analyzed by the researchers
      for major themes. Difficult tasks most frequently reported by caregivers were
      difficulties in helping with activities of daily living, managing incontinence,
      and handling patient's health problems. Patient's memory and behavioral problems
      most frequently causing difficulties in care were suspicion/accusation,
      forgetfulness, and wandering. Strategies which were most often used by caregivers
      to handle specific difficult tasks were environmental management and doing/fixing
      for the elderly subject; to handle patient's memory/behavioral problems were
      convincing them and going along with them. In overall caregiving strategies, care
      arrangement was most often used by caregivers. The findings of this study can
      sensitize the health providers to a wide variety of difficulties and problems
      caregivers of patients with dementia encounter. Health providers might be also
      more aware of the different strategies caregivers use in handling these
      difficulties and problems. Efforts can be put into helping families use more
      effective strategies when handling the behavioral problems and caregiving
      difficulties.

PMID- 8871290
TI  - [A cross-sectional study of factors associated with production of Japanese cedar
      pollen specific IgE antibody and total IgE antibody, and symptoms of Japanese
      cedar pollinosis in primary school children].
AB  - Frequency of and factors associated with sensitization by Japanese cedar pollen
      (JCP) and Japanese cedar pollinosis (JCPS) were analyzed by a cross-sectional
      method. Four hundred and five primary school children in a rural town were
      examined by a questionnaire filled out by their parents and a serum test in May,
      1994. Children with positive JCP specific IgE antibody (CAP-RAST score > = 1)
      comprised 39%, and those with a score of 2 or more, 35%. Prevalence of JCPS
      defined as positive IgE antibody and "definite symptoms" (any nasal and/or
      conjunctival symptom continuing for three weeks or more in March and/or April)
      was 8%, and that of JCPS defined as positive IgE antibody and "definite or
      possible symptoms" (no condition for duration) was 22%. Children with a high
      total IgE antibody level (> = 250 U/ml) comprised 26%. The JCP specific IgE
      antibody level revealed a strong positive correlation with the total IgE antibody
      level. Past and family history of allergic disease in general was associated with
      a total IgE antibody level stronger than the JCP specific IgE antibody level, and
      the history was also associated with allergic-like symptoms except for JCPS
      stronger than the symptoms of JCPS. Passive smoking by family and use of kerosene
      stove were negatively associated with the highest level of JCP specific IgE
      antibody and was not associated with other levels. One explanation may be that
      allergic disposition influences smoking habits, but the unique condition of nasal
      mucosa for allergic reaction should be considered.

PMID- 8871291
TI  - [Clinical significant correlation between to the onset of bronchial asthma in
      children and family history of allergic diseases. Part 2. The onset of allergic
      diseases of their parents and bronchial asthma in children].
AB  - Eighty asthmatic and 53 non-asthmatic children were evaluated in order to find
      out the relationship between the onset of bronchial asthma and allergic rhinitis
      of parents. The results are as it follows. Total serum IgE levels relate to
      current symptoms but not to the onset of parents' allergic diseases. Child-onset
      allergic diseases have more asthmatic children than adult-onset ones. Child has
      more asthma when either father or mother has asthma than allergic rhinitis. Child
      onset asthma of parents has higher incidence of asthma in children than child
      onset allergic rhinitis, adult-onset asthma and allergic rhinitis. We concluded
      that information on the onset of parents' allergic diseases could help us to
      predict bronchial asthma in their children, and both environmental and
      psychological factors is aggravating asthmatic attacks in children.

PMID- 8871292
TI  - [Bronchodilating effect of inhalation of aerosolized aminophylline in asthmatic
      patients].
AB  - Inhalation of aerosolized aminophylline solution (Neophylline) was examined for
      it's bronchodilating effect. Tests were done on the patient with bronchial asthma
      aged from 8 to 16 years of age which were divided into two groups, i.e., 21
      wheezy patients, 8 non-wheezy patients and on another 14 under normal controls.
      1.2 ml. of neophylline (30 mgs. of aminophylline) was inhaled to each patient by
      the micronebulizer for 6 minutes. VC, FEV1, PFR, V50 and V25 were measured by a
      Flow-volume recorder OST 7OD just before and after inhalation. The results showed
      that the bronchodilating effect of inhaled neophylline was detected in the wheezy
      patients group but not in the non-wheezy patients group nor in the control group.
      Furthermore, the duration of the bronchodilating effect was examined on another
      19 wheezy patients by a peak flow meter. The effect appeared to be sustained for
      4 hours after inhalation. Inhalation of serosolized neophylline is considered to
      be useful because of the fact that the bronchodilation can be obtained without an
      elevation of serum concentration of theophylline.

PMID- 8871293
TI  - [Clinical study of bronchial asthma in adult, intractable asthmatics after
      introduction of guideline therapy].
AB  - Introduction of Guideline for asthma treatment proposed by the committee of
      Japanese allergology have a tremendous impact on patients with bronchial asthma.
      Intractable asthmatics who have had to take some oral steroid to overcome disease
      severity, may have also some merit by this treatment, so that some of them might
      be no longer considered as intractable asthmatics. To clarify this, multicenter
      study was conducted. In this study, a case who have had more than 5 mg of
      prednisolone and/or 800 mu g of beclomethasone dipropionate throughout the year,
      was diagnosed as intractable asthmatics. In 845 case, 14.7%, 123 cases were
      diagnosed as intractable. These cases were significantly to be non-atopic and
      adult onset. Also, they have a significant tendency to be deteriorated by
      infection and careless drug administrations. Using the multiquantification method
      to examine the most powerful factor on intractable asthmatics, type of asthmatics
      was the most important and the past history of severe attack was the second. When
      intractable asthmatics diagnosed mainly by their BDP usage (BDP-intractable) were
      compared with intractable diagnosed by oral PSL (PSL-intractables), BDP
      intractables were significantly atopic compared to PSL-intractables.

PMID- 8871295
TI  - [A study of clinical significance of leukocyte migration inhibition test in drug
      induced hypersensitivity pneumonitis].
AB  - In 71 patients suspected of drug-induced pneumonitis, the identification of the
      allergenic drugs were studied by leukocyte migration inhibition test (LMIT). The
      LMIT was positive in 61 cases (85.9%). Leukocyte migration activating factor
      (LMAF) was detected in 22 cases (30.9%), and leukocyte migration inhibitory
      factor (LMIF) in 39 cases (54.9%), which was found significantly higher than LMAF
      (p < 0.05). There was no considerable difference in the LMIT-positive rate
      between interstial and eosinophilic pneumonia. The LMIT-positive drugs were
      detected in 66 of all 180 suspected drugs, in which 33 drugs (50%) were
      antibacterial agents and 11 were Kampo prescriptions. beta-Lactam antibiotics
      accounted for about half the number (16 drugs) in antibacterial agents. LMAF was
      detected more frequently in beta-lactam antibiotics-induced pneumonitis, which
      LMIF was detected more often in Kampo prescriptions-induced pneumonitis (p <
      0.005). Furthermore, the latent period from drug initial to the onset of
      pneumonitis were about 10 days in beta-lactam antibiotics-induced pneumonitis and
      a few months in Kampo prescriptions-induced pneumonitis (p < 0.001). Our findings
      indicate that LMIT is valuable to identify the allergenic drugs in drug-induced
      hypersensitivity pneumonitis and that delayed-type hypersensitivity (DTH), with
      which LMIF is related closely, plays a major role in the pathogenesis of this
      lung lesion. Furthermore, the pathogenic mechanism of beta-lactam antibiotics
      induced pneumonitis may be different from that of Kampo prescriptions-induced
      pneumonitis.

PMID- 8871294
TI  - [A comparative study of MAST and CAP RAST with 90 patients with bronchial
      asthma].
AB  - We measured serum IgE antibodies by the MAST and the CAP RAST in 90 patients
      refered to our asthma clinic and compared their results. Furthermore the patients
      with CAP positive/MAST negative were investigated by bronchial provocation test
      with allergen, skin test and CAP RAST inhibition test. Significant correlations
      were obtained between the results of the MAST and those of the CAP RAST for house
      dust 2 (r = 0.617), for Dermatophagoides farinae (r = 0.776) and for Japanese
      cedar (r = 0.609), but not for all 3 mold allergens. CAP positive/MAST negative
      results were found in 1.4-27.8% and MAST positive/CAP negative results were found
      in 0-2.7%. The presences of specific IgE antibodies were confirmed by a positive
      bronchial provocation test with allergen, skin test and CAP RAST inhibition test
      in CAP positive/MAST negative results. Those results indicate that the CAP RAST
      is more sensitive than the MAST.

PMID- 8871297
TI  - [A case of postinfectious chronic cough improved with bakumondo-to not with
      antihistamine and dextromethorphan hydrobromide].

PMID- 8871296
TI  - [The involvement of protein kinase C isozymes in activation of phospholipase D
      and secretion of serotonin in rat basophilic leukemia cells].
AB  - Western blot analysis shows the presence of protein kinase C (PKC) alpha, beta1,
      beta2, delta, epsilon, zeta isozymes in rat basophilic leukemia (RBL-2H3) cells.
      Antigen stimulation caused preferential translocation of protein kinase C (PKC)
      delta and epsilon to membranes. On the other hand, when the cells were stimulated
      by phorbol 12-myristate 13-acetate (PMA) or ionophore (A23187), PKCalpha and beta
      were predominantly translocated. Phospholipase D (PLD) was activated by three
      stimulants in order: A23187 > PMA >> antigen. Therefore, PKCalpha and beta seem
      to be involved in the activation of PLD in RBL cells. The translocation of all
      PKC isozymes in A23187 stimulation was weak. Therefore, PLD activation in A23187
      stimulation may require some other factors than PKC which are associated with the
      increase of Ca2+ in the cells. The cells stimulated by antigen secreted serotonin
      to the same level as the cells stimulated by A23187. In both stimulation,
      PKCalpha and epsilon were translocated to almost similar level, suggesting that
      PKCalpha and epsilon are involved in the secretion. All PKC isozymes except zeta
      were markedly translocated in PMA stimulation, but secretion did not occur. These
      results indicate that translocation of PKC alpha and beta may be associated with
      PLD activation and also that both translocation of PKCalpha and epsilon and
      intracellular calcium increase are required for serotonin secretion in RBL cells.

PMID- 8871298
TI  - [Cardiogenic shock].

PMID- 8871299
TI  - [Definition and diagnostic criteria of cardiogenic shock].

PMID- 8871300
TI  - [Etiology and physiopathology of cardiogenic shock--mechanism of circulatory
      regulation and disturbance of the function].

PMID- 8871301
TI  - [Humoral and metabolic changes in cardiogenic shock].

PMID- 8871302
TI  - [Reality of emergency treatment of cardiogenic shock].

PMID- 8871303
TI  - [Clinical symptoms of cardiogenic shock and important points in evaluating the
      severity].

PMID- 8871304
TI  - [Evaluation of the severity of cardiogenic shock by monitoring of their
      hemodynamics].

PMID- 8871305
TI  - [Important points in clinical tests for evaluating the severity of patients with
      cardiogenic shock].

PMID- 8871306
TI  - [Important points in diagnostic imaging for evaluation of patients with
      cardiogenic shock].

PMID- 8871307
TI  - [Prognostic evaluation of cardiogenic shock by the severity].

PMID- 8871308
TI  - [Emergency treatment of cardiogenic shock].

PMID- 8871309
TI  - [Therapy of cardiogenic shock due to myocardial infarction].

PMID- 8871310
TI  - [Therapy of cardiogenic shock due to arrhythmia].

PMID- 8871311
TI  - [Acute-phase therapy of cardiogenic shock and severe myocarditis using
      percutaneous cardiopulmonary support].

PMID- 8871312
TI  - [Cardiogenic shock due to cardiac tamponade].

PMID- 8871313
TI  - [Therapeutic countermeasures for cardiogenic shock in the aged].

PMID- 8871314
TI  - [Clinical application and management of assisted circulation in the treatment of
      cardiogenic shock].

PMID- 8871315
TI  - [Countermeasures for patients with cardiogenic shock (discussion)].

PMID- 8871316
TI  - [Case of renovascular hypertension with pheochromocytoma].

PMID- 8871317
TI  - [Case of tuberculous meningitis with hydrocephalus and hypothermia].

PMID- 8871318
TI  - [Father-son cases of arrythmogenic right ventricular dysplasia treated
      successfully by radiofrequency catheter ablation].

PMID- 8871319
TI  - [Case of thrombotic-occlusive type dissecting aneurysm appeared during the course
      of thoracic aortic aneurysm].

PMID- 8871320
TI  - [Hemodialysis case of kidney failure due to ruptured renal angiomyolipoma
      associated with tuberous sclerosis].

PMID- 8871321
TI  - [Recent topics on inflammatory myositis].

PMID- 8871322
TI  - [AIDS and tuberculosis].

PMID- 8871323
TI  - Genetic testing data.

PMID- 8871324
TI  - Chronic fatigue illness and Operation Desert Storm.

PMID- 8871325
TI  - Incidence and treatment of heat stroke.

PMID- 8871326
TI  - Environmental illness and multiple chemical sensitivity.

PMID- 8871327
TI  - What should the recommendations be concerning treatment and job placement for a
      nursing home employee diagnosed as having influenza?

PMID- 8871328
TI  - Postural stability assessment in sewer workers.
AB  - In this study, postural stability was measured with a microcomputer-based force
      platform as an indirect assessment of central nervous system effect in 28 sewer
      workers (age range 23.4 to 64.5 years, standard deviation of 8.7 years). All
      workers performed four 30-second postural sway tests. The organic-solvent
      exposure was measured by a photo-ionization detector. The photo-ionization
      detector was calibrated to measure volatile organic solvents in total benzene
      equivalence, and concentrations were measured in various parts of the plant. The
      mean exposure was .32 parts per million (ppm) benzene equivalent (range of .02 to
      .95 ppm, standard deviation .19 ppm). Based on a covariate adjusted linear
      multiple-regression model, a statistically significant (p < .05) positive
      correlation was demonstrated between postural sway and organic-solvent exposure.
      These workers also had increased postural sway compared with a nonexposed
      population. The statistically significant correlation between postural sway
      determinations and organic-solvent exposure was surprising given the very low
      exposures measured. It is possible that the organic-solvent exposure might not be
      the causative agent, but rather that the solvents themselves correlate with some
      other causative exposure, ie, total volatile organics as implicated in the cause
      of sick-building syndrome.

PMID- 8871329
TI  - Exposure in a household using gasoline-contaminated water.
AB  - Contamination of drinking water with petroleum products is an increasingly common
      problem. Physicians are often asked to advise patients about such exposures. This
      study assessed household exposure from gasoline-contaminated drinking water in a
      New England household. A sampling strategy was designed to estimate inhalation
      and ingestion exposure to benzene and three other aromatic hydrocarbons typically
      found in gasoline-contaminated water. The estimated inhaled doses of all agents
      were similar to the estimated ingested dose. Over half the inhaled dose of all
      four agents was associated with shower activities as was over half the estimated
      total dose by all routes of exposure. Under these conditions, discontinuing
      ingestion of water contaminated with these agents may decrease the dose of
      benzene by less than one third, whereas discontinuing both ingestion and
      showering may decrease the dose of benzene by over three quarters. This limited
      study suggests that routes of exposure other than ingestion are important and
      should receive attention in the regulatory and risk-assessment process.

PMID- 8871330
TI  - Balancing cost and precision in exposure assessment studies.
AB  - Because of the cost involved both for personnel and laboratory analyses, it is
      incumbent that industrial hygiene (IH) sampling plans be both precise and cost
      effective. The purpose of this paper is to describe a method of balancing two
      opposing objectives, increasing precision and decreasing the cost by manipulating
      the number and nature of IH sample collections. Data from a pilot study were used
      to obtain an optimum sampling scheme for exposure assessment. The design that
      obtains the highest precision while controlling costs serves as the model of
      choice. An approach is illustrated with data from an ongoing study examining
      health effects of workers exposed to solvents. It is shown that there is a large
      variation in precision for identical IH measurements, depending on the efficiency
      of the sampling schedule.

PMID- 8871331
TI  - Differentiation of the ILO boundary chest roentgenograph (0/1 to 1/0) in
      asbestosis by high-resolution computed tomography scan, alveolitis, and
      respiratory impairment.
AB  - High-resolution computed tomography (HRCT) scans have been advocated as providing
      greater sensitivity in detecting parenchymal opacities in asbestos-exposed
      individuals, especially in the presence of pleural fibrosis, and having excellent
      inter- and intraobserver reader interpretation. We compared the 1980
      International Labor Organization (ILO) International Classification of the
      Radiographs of the Pneumoconioses for asbestosis with the high-resolution CT scan
      using a grid scoring system to better differentiate normal versus abnormal in the
      ILO boundary 0/1 to 1/0 chest roentgenograph. We studied 37 asbestos-exposed
      individuals using the ILO classification, HRCT grid scores, respiratory symptom
      questionnaires, pulmonary function tests, and bronchoalveolar lavage. We used
      Pearson correlation coefficients to evaluate the linear relationship between
      outcome variables and each roentgenographic method. The normal HRCT scan proved
      to be an excellent predictor of "normality," with pulmonary function values close
      to 100% for forced vital capacity (FVC), forced expiratory volume in 1 second
      (FEV1), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLCO)
      and no increase in BAL inflammatory cells. Concordant HRCT/ILO abnormalities were
      associated with reduced FEV1/FVC ratio, reduced diffusing capacity, and
      alveolitis consistent with a definition of asbestosis. In our study, the ILO
      classification and HRCT grid scores were both excellent modalities for the
      assessment of asbestosis and its association with impaired physiology and
      alveolitis, with their combined use providing statistical associations with
      alveolitis and reduced diffusing capacity.

PMID- 8871332
TI  - Techno-stress: a prospective psychophysiological study of the impact of a
      controlled stress-reduction program in advanced telecommunication systems design
      work.
AB  - There is a void of studies concerning occupational health aspects from working
      with the most advanced forms of information technologies techniques such as are
      found in some of the world-renowned telecommunication systems development
      laboratories. However, many of these techniques will later be applied in the
      regular office environment. We wanted to identify some of the major stressors
      perceived by advanced telecommunication systems design employees and develop a
      valid and reliable instrument by which to monitor such stressors. We were also
      interested in assessing the impact of a controlled prospective stress-reduction
      program on perceived mental stress and specific psychophysiological parameters. A
      total of 116 employees were recruited. Sixty-one were offered to participate in
      one of three stress-reduction training programs (intervention group). The
      additional 50 functioned as a reference group. After a detailed baseline
      assessment, including a comprehensive questionnaire and psychophysiological
      measurements, new assessments were made at the end of the formal training program
      (+ 3 months) and after an additional 5-month period. Results reveal a significant
      improvement in the intervention group with regard to circulating levels of the
      stress-sensitive hormone prolactin as well as an attenuation in mental strain.
      Cardiovascular risk indicators were also improved. Circulating thrombocytes
      decreased in the intervention group. Type of stress-reduction programs chosen and
      intensity of participation did not significantly impact results. Coping style was
      not affected and no beneficial effects were observed with regard to the
      psychological characteristics of the work, eg intellectual discretion and control
      over work processes. The survey instrument is now being used in the continuous
      improvement of work processes and strategic leadership of occupational health
      issues. The results suggest that prior psychophysiological stress research, based
      on low- and medium-skill, rather repetitive kinds of jobs, may not be completely
      applicable to that of skilled professionals. The results indicate that cutting
      edge telecommunication systems design employees suffer from significant amounts
      of mental strain. In addition, there are limited but measurable benefits from a
      stress-reduction program. More attention should be directed as to how to design
      healthy and productive work environments in workplaces using advanced information
      technologies.

PMID- 8871333
TI  - Increased variability in bronchial responsiveness in aluminum potroom workers
      with work-related asthma-like symptoms.
AB  - In a longitudinal study, we studied the variability in bronchial responsiveness
      (BR) to methacholine in aluminum potroom workers suffering from work-related
      asthma-like symptoms (WASTH) and in symptom-free workers. In the index group, 26
      men suffering from WASTH were selected from a cross-sectional survey. The
      reference group comprised 45 symptom-free men recruited from the enrollment of
      new employees. Bronchial responsiveness was expressed as the dose-response slope
      (DRS) of the line through origin and the last data point. The standard deviation
      of the log-transformed DRS was positively associated with symptom score (P =
      .012) and the mean BR (P < .001). Our results indicate that the severity of
      respiratory symptoms in aluminum potroom workers with WASTH reflects the
      variability in BR.

PMID- 8871334
TI  - Machinery-related occupational fatalities in the United States, 1980 to 1989.
AB  - The National Traumatic Occupational Fatalities surveillance system identified
      machinery-related incidents as the second leading cause of traumatic occupational
      fatalities in the United States between 1980 and 1989. These incidents resulted
      in 8,505 civilian worker deaths and an average annual fatality rate of .80 per
      100,000 workers. Workers aged 65 years and older had 5.8 times the fatality rate
      of workers aged 16 to 64 years (4.06 vs. 70). The highest industry-specific rate
      was noted in agriculture, forestry, and fishing (7.47). Tractors and other
      agricultural machinery were associated with nearly 9 of every 10 fatal machinery
      related incidents involving workers aged 65 or older. Although numerous studies
      of agricultural machinery-related fatalities are found in the literature,
      detailed analyses of machinery-related fatalities in the construction industry as
      well as analyses of work situations and risk factors associated with fatal
      injuries are needed.

PMID- 8871335
TI  - Causation, impairment, disability: an analysis of coal workers' pneumoconiosis
      evaluations.
AB  - The relation of exposure, impairment, and awarded disability in coal dust disease
      cases is often unclear. Surveillance data from large mining populations has
      demonstrated a decline in pulmonary function associated with coal dust exposure,
      even in miners with normal roentgenographs, though the frequency with which this
      results in impairment is not well defined. This study examines a more specific
      group, 374 disability claimants, for whom evaluation data is less extensive. In
      this group, several pulmonary function variables declined in association with
      years mining, even after controlling for roentgenograph status and smoking. This
      was particularly seen among underground miners, although the declines were small
      and of marginal statistical significance. Awards were evaluated for 203 resolved
      cases. Among 59 with completely normal roentgenographs and pulmonary function
      tests (PFTs), 38 (64%) received some disability award. These findings support
      development of a more rational impairment/disability system for those with
      potential coal dust disease.

PMID- 8871336
TI  - ACOEM reproductive hazard management guidelines. American College of Occupational
      and Environmental Medicine.

PMID- 8871337
TI  - Hypnotherapy treatment for dysphagia.
AB  - A case history is reported to illustrate the successful use of hypnotherapy in
      the treatment of dysphagia. A 60-year-old cancer patient was aided in swallowing
      and preparation for dilatation of esophageal strictures. The use of more than one
      therapist is discussed as an effective strategy in treatment.

PMID- 8871338
TI  - Self-hypnotic relaxation during interventional radiological procedures: effects
      on pain perception and intravenous drug use.
AB  - The authors evaluated whether self-hypnotic relaxation can reduce the need for
      intravenous conscious sedation during interventional radiological procedures.
      Sixteen patients were randomized to a test group, and 14 patients were randomized
      to a control group. All had patient-controlled analgesia. Test patients
      additionally had self-hypnotic relaxation and underwent a Hypnotic Induction
      Profile test. Compared to controls, test patients used less drugs (0.28 vs. 2.01
      drug units; p < .01) and reported less pain (median pain rating 2 vs. 5 on a 0-10
      scale; p < .01). Significantly more control patients exhibited oxygen
      desaturation and/or needed interruptions of their procedures for hemodynamic
      instability. Benefit did not correlate with hypnotizability. Self-hypnotic
      relaxation can reduce drug use and improve procedural safety.

PMID- 8871339
TI  - Action and desire in posthypnotic responding.
AB  - The authors examined the impact of suggestion focus and test type on the
      posthypnotic responding of high hypnotizable participants. The posthypnotic
      suggestion focused on either behavior (action) or experience (desire);
      posthypnotic responding was indexed in a formal test, an embedded test, and an
      informal test. In Experiment 1, the posthypnotic suggestion involved a motor act.
      Participants given the action suggestion were more likely to respond completely
      on the formal test than participants given the desire suggestion. Also,
      responding declined across the three tests; suggestion focus influenced
      responding on the informal but not the embedded test. In Experiment 2, the
      posthypnotic suggestion involved a verbal act. In contrast to Experiment 1,
      participants given the action or desire suggestion responded similarly on the
      formal test. As in Experiment 1, responding declined across the three tests;
      however, suggestion focus did not influence responding on the embedded or the
      informal tests. The findings highlight the meaningful effects of changes in what
      the hypnotist says, what participants are asked to do, and how their responses
      are assessed.

PMID- 8871340
TI  - Danish norms for the Harvard group scale of hypnotic susceptibility, form A.
AB  - Norms for a Danish adaptation of the Harvard Group Scale of Hypnotic
      Susceptibility, Form A (HGSHS:A) are presented. Four samples tested from 1988 to
      1991 (n = 166, n = 54, n = 95, and n = 61) were pooled, resulting in an aggregate
      sample of 376 participants. The normative data were generally congruent with
      earlier normative studies with regard to score distribution, item difficulty
      levels, and reliability. Studies using the Danish adaptation of the HGSHS:A as a
      screening instrument have shown the predictive value of the instrument in a
      Danish context. Data for a comparable American sample of volunteers (n = 170)
      tested by the same hypnotist were included in the analysis. A comparison revealed
      a marked difference for the posthypnotic suggestion item, hinting that cultural
      differences between the Danish and American samples with regard to expectancies
      and attitudes toward hypnosis may play a role. Further studies comparing
      attitudes toward hypnosis across different cultural contexts are needed to
      clarify this issue.

PMID- 8871341
TI  - Comprehension of reversible sentences in "agrammatism": a meta-analysis.
AB  - The functional source(s) of agrammatic aphasic patients' difficulty comprehending
      semantically reversible active and passive sentences was investigated in a meta
      analysis of published sentence/picture matching data from patients with
      agrammatic production. The analysis revealed approximately equal distributions of
      three distinct patterns of performance on active and passive voice sentences
      relative to what would be expected by chance: both structures comprehended better
      than chance; both structures comprehended no better than chance; active voice
      sentences comprehended better than chance, while passive voice sentences were
      comprehended at levels no better than (or worse than) chance. These results are
      in conflict with explanations of aphasic sentence comprehension failure in which
      a single pattern of relative performance on active and passive voice structures
      is asserted to be characteristic of the comprehension of all agrammatic speakers.
      They also highlight the difficulty of identifying any single causal factor to
      account for sentence comprehension failure in patients with "agrammatic" sentence
      production. Results are interpreted with regard to the role of data from aphasic
      patients in the testing of hypotheses about the organization of normal language
      processes.

PMID- 8871342
TI  - Interaction with autonomy: multiple output models and the inadequacy of the Great
      Divide.
AB  - There are currently a number of psycholinguistic models in which processing at a
      particular level of representation is characterized by the generation of multiple
      outputs, with resolution--but not generation--involving the use of information
      from higher levels of processing. Surprisingly, models with this architecture
      have been characterized as autonomous within the domain of word recognition but
      as interactive within the domain of sentence processing. We suggest that the
      apparent confusion is not, as might be assumed, due to fundamental differences
      between lexical and syntactic processing. Rather, we believe that the labels in
      each domain were chosen in order to obtain maximal contrast between a new model
      and the model or models that were currently dominating the field. The
      contradiction serves to highlight the inadequacy of a simple autonomy/interaction
      dichotomy for characterizing the architectures of current processing models.

PMID- 8871343
TI  - Similar, and similar concepts.
AB  - This paper analyzes English symmetrical predicates such as collide and match. Its
      point of departure is an analysis of the concept 'similar' from Tversky (1977)
      that appears to show that similarity is psychologically asymmetrical. One basis
      for this claim from Tversky is that the sentences North Korea is similar to Red
      China and Red China is similar to North Korea are assessed as differing in
      meaning by experimental subjects; this seems to imply that the symmetrical
      entailment (R x, y <--> R y, x) fails for this concept. Five experiments are
      presented that show: (1) the apparent asymmetry of similar is reproduced for 20
      predicates that are intuitively thought to be symmetrical, including equal and
      identical; (2) unique linguistic-interpretative properties hold for these
      symmetrical words, such as reciprocal interpretation when they appear
      intransitively, for example, North Korea and Red China are similar; (3) the
      asymmetrical interpretation of subject-complement constructions containing the
      symmetrical words is a consequence of general linguistic-interpretive principles.
      On the basis of the experimental findings, we offer an analysis of symmetrical
      predication. One major claim of the analysis is that symmetry is a property of
      lexical items and has no special syntax, that is, that John meets is semantically
      but not syntactically anomalous. A second claim is that the structural
      positioning of noun phrases in sentences containing symmetricals--rather than
      inherent semantic properties of the noun phrases themselves--sets their status as
      Figure and Ground (as described by Talmy, 1985) or Variant and Referent (as
      described by Tversky, 1977) in the comparison, even if the nouns are nonsense
      items. Finally, the behavior of symmetrical predicates is shown to vary as a
      function of their differing lexical class assignments and collateral semantic
      designations, such as activity versus state. Most generally, it is claimed that a
      deeper understanding of symmetrical terms comes from analyzing the semantics of
      syntactic structures in which they appear.

PMID- 8871344
TI  - TCR usage in human and experimental demyelinating disease.

PMID- 8871345
TI  - Recent advances in the pathogenesis of reactive arthritis.

PMID- 8871346
TI  - Broken dogma: penetration of autoantibodies into living cells.

PMID- 8871348
TI  - Bypassing the antigen to control rheumatoid arthritis.

PMID- 8871347
TI  - Genetic diversity of HLA-A2: evolutionary and functional significance.

PMID- 8871349
TI  - Immune regulation: a critical link between NK cells and CTLs.

PMID- 8871350
TI  - The structure and ligand interactions of CD2: implications for T-cell function.

PMID- 8871352
TI  - Engineered APCs for tumor immunotherapy.

PMID- 8871351
TI  - PI 3-kinase: a pivotal pathway in T-cell activation?

PMID- 8871353
TI  - The role of RGD in CD23-mediated cell adhesion.

PMID- 8871354
TI  - Chemokine receptors and chemokine-inducing molecules of lymphotropic
      herpesviruses.

PMID- 8871355
TI  - The kappa:lambda ratio of immature B cells.

PMID- 8871356
TI  - Effects of hypnosis on the immune response: B-cells, T-cells, helper and
      suppressor cells.
AB  - This study tested the effects of hypnosis on the immune response. High and low
      hypnotizable Ss were exposed to hypnosis, relaxation or control conditions. Blood
      samples obtained before treatment and twice thereafter were subjected to flow
      cytometry analysis. Significant alteration of the immune response as measured by
      B-cells and helper T-cells was shown only for highly hypnotizable Ss exposed to
      hypnosis.

PMID- 8871357
TI  - Subjective assessment of allergy relief following group hypnosis and self
      hypnosis: a preliminary study.
AB  - Self-hypnosis was taught to 34 self-identified allergy patients who attended two
      training classes. They practiced on their own and were questioned two months
      later. Seventy-six percent of the subjects reported they felt an improvement in
      their symptoms; 86% of those who were medicated decreased their medicines.
      Practice was clearly related to reported improvement. "Feeling hypnotized" was
      not related to improvement.

PMID- 8871358
TI  - Decoding mystifying signals: translating symbolic communications of elusive ego
      states.
AB  - Traditionally, Ego-state Therapy has been conducted with parts of the personality
      that have been activated hypnotically and that present themselves for verbal
      interaction. This paper presents two cases in which ego states communicate
      through symbolic and sensory signals at significant points in therapy.
      Recognition of the meaning and usefulness of these phenomena allows otherwise
      enigmatic material to provide crucial information about the patient's deepest
      struggles. Failure to identify this material can often precipitate therapeutic
      stalemates when the patient's most creative expressions go unnoticed. Effective
      utilization of these states can often bring about dramatic resolution of inner
      conflict and achieve symptom relief.

PMID- 8871359
TI  - Dissociative and hypnotic experiences in eating disorder patients: an exploratory
      study.
AB  - Hypnotizability, subjective experiences during hypnotizability assessment, and
      dissociation were studied in 53 eating disorder patients in order to explore the
      relationship between these phenomena. Dissociation was measured with a newly
      developed self-reporting Dissociation-Questionnaire (DIS-Q), level of
      hypnotizability was assessed with the Stanford Hypnotic Clinical Scale (SHCS),
      subjective experiences during hypnosis with the Dutch Phenomenology of
      Consciousness Inventory (DPCI), and the Dutch Resistance to Hypnosis Scale
      (DRHS). Compared with normals, eating disorder patients scored significantly
      higher on the DIS-Q and SHCS. Compared with restricting anorexics, anorexics of
      the mixed type as well as bulimics report higher scores on both the DIS-Q and
      SHCS, but a significant difference was found only for the DIS-Q subscale loss of
      control. Although positive correlations between the DIS-Q and SHCS were found,
      the magnitude of the correlations shows that both instruments probably are
      measuring different constructs. Some implications of these findings are
      discussed.

PMID- 8871360
TI  - Our bodies, our selves: treating the somatic expressions of trauma with ego-state
      therapy.
AB  - Trauma activates primitive defenses which often involve somatic processes. In
      this paper, the author explores the use of somatic approaches to ego-state
      therapy, developed by John and Helen Watkins (1979), which has been shown in the
      literature to be an effective method of treating the internal fragmentation and
      dissociated response patterns related to early childhood trauma. Through the use
      of hypnotic techniques such as the somatic bridge, ideosensory signalling, and
      sensory awareness training, ego-state therapy can be directed to those parts of
      the self which are more connected to somatic expressions of traumatic
      experiences. Several clinical case examples are presented to illustrate the
      potential of this approach in the treatment of trauma. Specific benefits for
      patients who complain of psychosomatic symptoms are discussed, as well as for
      those with compromised body image and perception, and its usefulness as a
      hypnoanalytic tool for uncovering memories that may be more somatically based.

PMID- 8871361
TI  - The eye-roll sign and the PAS dissociation scale.
AB  - In the past decade we have seen many new articles devoted to the study of
      dissociation and its implications in health and illness. The area of dissociative
      disorders received special attention with many authors pointing out the
      probability that dissociative disorders may, in fact, be much more pervasive than
      used to be thought. The need for a reliable measurement of dissociation has
      become more acute. This paper reports the results of a study comparing the
      Perceptual Alteration Scale (PAS), a behavioral scale measuring dissociation
      capacity, with Spiegel's Eye-Roll Sign (ERS) a postulated biological marker for
      the capacity to dissociate. 107 subjects' PAS scales and eye-roll sign
      measurements were analyzed. The results showed a mean PAS score of 155, and a
      mean eye-roll of 3.7. The Pearson Correlation Coefficients were computed for the
      eye-roll scores vs. the PAS scores, and showed a correlation of 0.55, with a
      significance of p < 0.0001. These results indicate a high positive correlation
      between the eye-roll sign and the PAS, spanning through the entire dissociative
      continuum. Further studies are needed to correlate the eye-roll sign with the
      Dissociative Experiences Scale (DES), and other measurements of dissociation.

PMID- 8871362
TI  - Manual-based treatments: the clinical application of research findings.
AB  - In addition to their now required use in controlled outcome studies, treatment
      manuals offer important advantages for clinical practice. Manual-based treatments
      are often empirically-validated, more focused, and more disseminable. They are
      useful in the training and supervision of therapists. Criticisms of manual-based
      treatments center on five main themes: they are conceptually at odds with
      fundamental principles of cognitive-behavioral therapy; they preclude idiographic
      case formulation; they undermine therapists' clinical artistry; they apply
      primarily to research samples which differ from the patients practitioners treat;
      and they promote particular 'schools' of psychological therapy. This paper
      emphasizes the inherent limitations of idiographic case formulation. It is argued
      that treatment manuals are consistent with an actuarial approach to assessment
      and therapy, which, on average, is superior to individual clinical judgment.
      Available data suggest that standardized treatment is no less effective than
      individualized therapy. Manual-based treatment demands therapist skill in its
      implementation. In suitably chosen therapists these skills are more a function of
      training than amount of clinical experience. Treatment manuals are likely to
      encourage a pragmatic approach to therapy and should not discourage clinical
      innovations.

PMID- 8871364
TI  - Factorial dimensions and correlates of blood, injury, injection and related
      medical fears: cross validation of the medical fear survey.
AB  - The Medical Fear Survey (MFS) and its companion scale, the Medical Avoidance
      Survey (MAS) were factor analyzed and the factor analysis was cross validated in
      sample of 934 participants. Seven reliable factors were derived from the MFS
      which cover the domain of blood, injury, and injection fears and phobias. These
      factors were entered into a discriminate analysis to predict blood injury-related
      fainting. The single factor, "fear of injections and blood draws" accounted for
      the majority of the MFS prediction of fainting, correctly classifying 72% of the
      fainters and 47% of non-fainters. The factors were examined in composite and
      individually in relation to gender and fainting. Overall, females and fainters
      scored significantly higher on the MFS although there was some variability.
      Implications for assessment and conceptualization of blood, injury, injection
      fears and phobias are discussed.

PMID- 8871363
TI  - The effects of video feedback on the self-evaluation of performance in socially
      anxious subjects.
AB  - Previous research has demonstrated that socially anxious subjects appraise their
      own social performance as worse than it is seen by independent observers, but are
      able to appraise the performance of others accurately. Three studies are reported
      in which socially anxious subjects evaluated their own social performance after
      viewing it via video. In each study, ratings made following video were closer to
      those made by independent observers than were ratings made without the benefit of
      video. In addition, this effect was similar in both socially anxious and
      nonanxious people. A model is proposed in which self evaluation of one's social
      performance is based on a mental representation of one's external appearance
      which receives input from long term memory, internal cues, and external cues.

PMID- 8871365
TI  - Is there a specific relationship between asthma and panic disorder?
AB  - The objective of the present study was three-fold: (1) to assess the prevalence
      of PD in asthmatic patients in comparison with non-asthmatic patients; (2) to
      investigate possible differences in pulmonary function and anxiety symptomatology
      between asthmatic patients with PD and those without; and (3) to evaluate
      possible differences in symptom perception during histamine-induced
      bronchoconstriction between asthmatic patients with PD versus asthmatic controls
      without PD matched for age, sex and bronchial responsiveness to histamine (PC20).
      The study was performed on 123 consecutive patients referred to the lung function
      laboratory of a university hospital for a histamine challenge test. Firstly,
      baseline measures for FEV1, anxiety (ADIS-R, ACQ, BSQ, and STAI) and depression
      (SDS) were collected. Subsequently, before and during induced bronchoconstriction
      FEV1, perceived breathlessness (Borg scale), subjective anxiety (SUDS), and
      somatic panic symptoms (PAQ) were assessed. The prevalence of PD in asthmatic
      patients, although higher than in the general population, was very similar to the
      rate observed in non-asthmatic patients. Baseline level of FEV1 and bronchial
      responsiveness to histamine (PC20) were also not significantly different between
      asthmatic patients with and without PD. Moreover, in comparison with matched
      controls, PD cases reported significantly higher levels of perceived
      breathlessness during induced bronchoconstriction, although their mean fall in
      FEV1 was very comparable. It is concluded that the higher prevalence of PD in
      asthma is non-specific and probably due to selection bias.

PMID- 8871366
TI  - A cognitive-behavioral model of compulsive hoarding.
AB  - Compulsive hoarding is a little studied phenomenon within the research
      literature. The information available on compulsive hoarding is diverse and not
      well integrated. In the present article we propose a tentative cognitive
      behavioral model of compulsive hoarding. The purpose of such a model is to
      provide a framework for the development and testing of hypotheses about
      compulsive hoarding. In this model hoarding is conceptualized as a multifaceted
      problem stemming from: (1) information processing deficits; (2) problems in
      forming emotional attachments; (3) behavioral avoidance; and (4) erroneous
      beliefs about the nature of possessions. Specific hypotheses about each of these
      are discussed.

PMID- 8871367
TI  - Cognitive therapy for punishment paranoia: a single case experiment.
AB  - There is growing agreement that at least certain kinds of delusions defend
      against negative self-evaluation, and in consequence that cognitive therapy for
      delusions needs to address issues of self-evaluation more explicitly. However, in
      practice it can be difficult to enable clients to see the connection between
      delusions and self-esteem. The present single-case study exemplifies the
      conceptual and practical application of cognitive therapy for individuals who are
      both paranoid and have strong negative self-evaluative beliefs. A multiple
      baseline approach is used, whereby one man's negative self-evaluative belief and
      two paranoid delusions are challenged sequentially. Conviction in two of the
      three beliefs changes at the point of intervention; conviction in the third
      changes prior to intervention. We discuss the details of the case, as well as the
      wider implications for cognitive approaches to delusions.

PMID- 8871368
TI  - Chronic emotional processing in survivors of the Herald of Free Enterprise
      disaster: the relationship of intrusion and avoidance at 3 years to distress at 5
      years.
AB  - Thirty-seven survivors completed the Impact of Event Scale (IES), a measure of
      intrusive and avoidant activity, at around 3 yr following the Herald of Free
      Enterprise disaster. The aim of the present study was to examine the relationship
      between scores on the IES to scores on the Beck Depression Inventory (BDI) and
      the Spielberger State Anxiety Inventory (STAI-Y1) at around 5 yr subsequent to
      the event. Higher scores on the IES were able to predict higher scores on the BDI
      and the STAI-Y1 over and above scores on the 28-item General Health Questionnaire
      (GHQ-28) which was also administered at around 3 yr on from the event.
      Implications for cognitive-behaviour therapy are discussed.

PMID- 8871369
TI  - Compulsive washing in the absence of phobic and illness anxiety.
AB  - A new typology of washing compulsions has been proposed: those that arise from a
      sense of dirtiness, those that arise from a sense of mental pollution, and
      finally, those that arise from a fear of illness. A case series is reported
      suggesting that a further class of washing behaviour can be described
      attributable to the personality trait of perfectionism.

PMID- 8871370
TI  - The nature and assessment of catastrophic thoughts in panic disorder.
AB  - This essay describes the current status of our conceptualization and assessment
      of catastrophic thoughts in panic disorder, an area that is more heterogeneous
      than may first appear. It is suggested that a heuristic approach would involve
      assessing both 'state' catastrophic cognitions (automatic thoughts) and the
      underlying 'trait' cognitive factors (beliefs). The cognitive symptoms listed in
      the DSM-IV and the self-report Anxiety Sensitivity Index serve as useful
      preliminary measures for assessing these respective domains. The trait cognitive
      domain is seen as multidimensional and congruence is required with internal or
      external stimuli in producing state catastrophic thoughts and accompanying panic
      attacks. Pressing challenges and controversies in this field are also highlighted
      and strategies for potentially resolving these issues are offered. Accordingly,
      several directions for future investigation are presented throughout the paper.
      Examples of innovative assessment techniques are briefly described.

PMID- 8871371
TI  - The inventory of dyadic heterosexual preferences: development and psychometric
      evaluation.
AB  - This article describes the development and evaluation of an instrument that
      measures preferences for specific sexual behaviors of heterosexual men and women
      in a dyadic context. In Study 1, 74 statements of preference were reduced to 46
      on the basis of reliability and range of responses. Factor analysis revealed that
      27 of the 46 items loaded on 6 factors: Erotophilia, Use of Contraception,
      Conventionality, Use of Erotica, Use of Drugs/Alcohol, and Romanticism. In Study
      2, factor analysis of fresh data from a second sample cross-validated these
      results. To establish construct validity of the revised 27-item Inventory of
      Dyadic Heterosexual Preferences (IDHP), relationships between each of its 6
      scales and 6 criterion measures were examined. These analyses suggested that the
      last scale is more accurately characterized by the term Romantic Foreplay. We
      conclude that the IDHP measures 6 distinct domains of sexual preference with a
      brief, psychometrically sound instrument. Potential applications of the IDHP,
      suggestions for future research, and strengths and limitations of the current
      investigation are discussed.

PMID- 8871372
TI  - Viewing time as a measure of sexual interest among child molesters and normal
      heterosexual men.
AB  - Although phallometric assessment is the best scientific method for measuring male
      sexual interest, it is intrusive and highly technical. We examined viewing time
      as an unobtrusive and technically simple measure of sexual preference and
      compared the discrimination obtained by viewing time measures with that obtained
      by phallometric measures. Slides of nude males and females of various ages were
      shown to child molesters and normal men while their viewing times were recorded.
      Subjects then rated the sexual attractiveness of the stimulus persons.
      Phallometric assessments using the same stimulus categories were also given to
      some of the Ss. Deviance scores calculated from the viewing time data
      significantly discriminated between the child molesters and the normals, although
      the discrimination achieved was less than that obtained using phallometric
      measures. Sexual attractiveness ratings did not differentiate the two groups.
      Among the normal men, viewing time and sexual attractiveness ratings were highly
      correlated; but the correlation was much lower for child molesters. Viewing time
      shows considerable promise as an unobtrusive measure of male sexual interest.

PMID- 8871373
TI  - Commentary on "Evaluation of canines for accelerant detection at fire scenes" (J
      Forensic Sci 1994 Nov; 39(60):1528-1536)--sensitivity vs. specificity.

PMID- 8871374
TI  - Commentary on Leong GB and Silva JA. A psychiatric-legal analysis of psychotic
      criminal defendants charged with murder (J Forensic Sci 1995;40(3):4045-448)

PMID- 8871375
TI  - A Bayesian approach to adult human age estimation from dental observations by
      Johanson's age changes.
AB  - Much of the data which appears in the forensic and archaeological literature is
      ordinal or categorical. This is particularly true of the age related indicators
      presented by Gustafson in his method of human adult age estimation using the
      structural changes in human teeth. This technique is still being modified and
      elaborated. However, the statistical methods of regression analysis employed by
      Gustafson and others are not particularly appropriate to this type of data, but
      are still employed because alternatives have not yet been explored. This paper
      presents a novel approach based upon the application of Bayes' theorem to ordinal
      and categorical data, which overcomes many of the problems associated with
      regression analysis.

PMID- 8871376
TI  - A survey of gunshot residue analysis methods.
AB  - A survey was sent to 80 forensic laboratories in 44 States and two Canadian
      Provinces concerning methodology in analyzing gunshot residue (GSR) and
      interpreting the results. Of the 80 surveys, 50 (63%) were returned completed.
      Questions included standard procedures, collection methods, thresholding problems
      and specificity of data. These results are compared to a previous survey reported
      in 1990. Implications for the interpretation and future study of these methods
      are discussed.

PMID- 8871377
TI  - Postgraduate forensic science education in Turkey.
AB  - Legal medicine in Turkey, has an educational background that goes back to 1839
      and the first autopsy in modern terms was performed in 1841. In the early days,
      it was common practice for those involved in this work to extend their
      investigative knowledge into areas not directly concerned with medical matters.
      However forensic medical investigations cannot be entrusted in the hands of
      single investigators, but should rather be dealt with by cooperative groups of
      experts nowadays. This need was the major force for the establishment of the
      Institute of Legal Medicine and Forensic Sciences by a special article of the law
      (section 2547) as a training and research center in 1982. The Institute being the
      first and only institution giving master's and doctorate degrees in Forensic
      Sciences, has 3 major departments: 1) Medical Sciences Department, 2) Basic
      Sciences Department and 3) Social Sciences Department. Graduates of various
      fields ranging from medical doctors specialized in any field, biologists,
      chemists to lawyers, district attorneys, psychologists and other related fields
      are composing the multidisciplinary structure of the institute. The main research
      fields of the Institute are: population genetics, paternity investigation, child
      abuse, and identification of human remains.

PMID- 8871378
TI  - Poppy seeds: differences in morphine and codeine content and variation in inter-
      and intra-individual excretion.
AB  - Poppy seeds from seven different origins (Dutch, Australian, Hungarian, Spanish,
      Czech, and two Turkish) were analyzed for the amount of opiates present. Four
      grams of each kind of seeds, equivalent to the amount of seeds on two bagels,
      were ingested by volunteers. One volunteer also ingested four times the same
      amount of poppy seeds from the same origin (Spanish). During 24 hours urine
      samples were obtained and screened for the presence of morphine and codeine using
      the FPIA technique (cut-off = 200 ng/mL) and a GC/MS confirmation with a limit of
      detection (LOD) of 25 ng/mL for codeine and morphine. Poppy seeds from different
      origins contain a wide variation of morphine (2-251 micro g/g) and codeine (0.4
      57.1 micro g/g) content. No other opiate could be detected. After ingestion a
      large interindividual variation of excretion of opiates exists. The testing
      results from the same kind of seeds ingested four times with a one week interval
      by the same volunteer also show a poor reproduceability. Several kinds of poppy
      seeds can give positive testing results (Australian, Hungarian, Spanish and one
      kind of Turkish seeds). Within 24 hours all testing results became negative.

PMID- 8871379
TI  - High-performance liquid chromatographic analysis with fluorescence detection of
      ethyl centralite and 2,4- dinitrotoluene in gunshot residues after derivatization
      with 9-fluorenylmethylchloroformate.
AB  - A reversed-phase high-performance liquid chromatographic method using 9
      fluorenylmethylchloroformate (FMOC) as fluorogenic labeling reagent for the
      detection of ethyl centralite (EC) and 2,4-dinitrotoluene (2,4-DNT) in gunshot
      residues is reported. Residues were sampled with cotton wool swabs which were
      then extracted and the extracts cleaned by TLC. The sample spots on the TLC plate
      were scraped off and extracted to recover the analytes. The extract corresponding
      to EC was hydrolyzed while 2,4-DNT was reduced. The hydrolysis and reduction
      products (N-ethylaniline and 2,4-diaminotoluene, respectively) were derivatized
      with FMOC in alkaline buffer solution at 52 degrees C for 20 min. The derivatives
      were analyzed by a reversed-phase HPLC with fluorescence detection. The detection
      limits for EC and 2,4-DNT were 200 pg and 1 ng per standard sample, respectively.
      Three out of eleven kinds of gunpowders analyzed were found to contain EC, while
      another three were found to contain 2,4-DNT. According to the results of
      gunpowder analysis, two different kinds of ammunition, which were presumed to
      contain EC in one and 2,4-DNT in the other, were chosen for test firings. Ethyl
      centralite was detected in cotton swabs sampled from spent cartridge cases of
      both of these two kinds of ammunition, but 2,4-DNT was not detected in any of
      these spent cases. Nine out of twelve samples swabbed from shooting hands at
      various times after firing two rounds of either kind of ammunition were found to
      contain EC, while none of these swabs were found to contain 2,4-DNT. The
      quantities of EC recovered from these hand swabs were shown to be in the range of
      0.6 to 4.0 ng.

PMID- 8871381
TI  - Long-term validation study of bitewing dental radiographs for forensic
      identification.
AB  - The validity of dental bitewing radiographs for forensic identification, with
      time lapses between the antemortem and postmortem film of up to 30 years, was
      tested. The ability to match radiographs from the same subject was expressed
      using sensitivity and specificity statistics. Although the overall accuracy of
      the observers was extremely high, it was obvious that radiographs from the same
      individual, when separated by time intervals greater that 20 years, had
      significantly reduced accuracy.

PMID- 8871380
TI  - Postmortem distribution and redistribution of morphine in man.
AB  - This study evaluated both site dependent differences and time dependent changes
      in postmortem morphine concentrations in man. In 32 deaths involving morphine,
      left ventricular blood, femoral blood, and cisternal cerebrospinal fluid, were
      collected as soon after death as possible (T1), and collected again together with
      iliac blood at the time of autopsy (T2). Samples were analyzed for morphine by
      radioimmunoassay. No evidence was found for changes in morphine concentration
      with respect to time at either central or peripheral sites, or in the
      cerebrospinal fluid. Ventricular blood morphine concentrations were however
      consistently higher than those in the peripheral compartment, represented by
      either femoral or iliac blood. This was particularly true when the ventricular
      morphine concentration exceeded 0.300 mg/L. At peripheral sites, femoral and
      iliac blood morphine concentrations were well correlated with each other, making
      either an appropriate site for collection of peripheral blood for toxicological
      testing.

PMID- 8871382
TI  - Co-morbidity of alcoholism and the paraphilias.
AB  - Alcoholism has been related to a wide variety of crimes. Various authors have
      studied the prevalence of alcoholism in relationship to incest, rape and
      pedophilia. This study evaluates the co-morbidity of alcoholism and the specific
      paraphilias including sexual sadism, fetishism, incest, pedophilia, exhibitionism
      and transvestism. Rapists were included although by definition it is not strictly
      a paraphilic disorder. Seven hundred and twenty eight paraphilic individuals were
      evaluated. More than 50% of sexual sadists were alcoholics. Alcoholism in
      association with sexual sadists was statistically significant as compared to
      transvestites, rapists, pedophiles, and incest offenders. Transvestism had the
      lowest relative rate of alcoholism. The authors discuss these findings and the
      role alcoholism plays in causing violent sexual behavior in individuals with
      paraphilias.

PMID- 8871383
TI  - Medically serious suicide attempts in a jail with a suicide-prevention program.
AB  - A suicide prevention program was implemented at the Galveston County Jail in
      1986, reducing the number of suicides to only one from that time until the
      present. In the ten years prior to the implementation of the program, there had
      been seven suicides. Nevertheless, there have been a number of cases of medically
      serious suicide attempts that have occurred since implementation of the program.
      Thirteen cases of suicide attempts severe enough to warrant transfer to an
      emergency room for medical attention were identified through jail incident
      reports as occurring between 1989, when improvements were made in record-keeping
      at the jail, and July of 1994, when this study was initiated. Hospital records,
      jail medical records, jail administrative records and, in some cases, competency
      evaluations were obtained for each case. The cases were examined regarding
      demographic data, psychiatric history, circumstances surrounding the act, and
      results of psychiatric evaluation performed after the act. The findings were then
      compared to studies of suicides and near-suicides in the literature. Examination
      of these cases has provided information that should render the suicide prevention
      program even more effective as well as provide useful information to other jails
      interested in implementing or improving a suicide-prevention program.

PMID- 8871384
TI  - Deaths due to foreign body aspiration in children: the continuing hazard of toy
      balloons.
AB  - Asphyxia due to aspiration of a foreign body is a common cause of accidental
      death in children. Foreign body aspiration is the most likely cause of accidental
      fatalities in children under 1-year-of-age. Children may die due to airway
      obstruction by food objects such as hot dogs, nuts, candies, grapes, seeds, and
      egg shells. Non-food objects such as balloons, coins, pop tops of beverage cans,
      pills, safety pins, ball bearings, marbles, and baby powder also may be fatally
      aspirated. To better understand and help prevent this well recognized health risk
      to children, we reviewed 10 years of cases at the Cook County Medical Examiner's
      Office in which deaths in children 14-years-of-age and younger were due to
      aspiration of foreign objects. The most common item that caused fatal aspiration
      in our series was a toy balloon.

PMID- 8871385
TI  - Fatal light aircraft accidents in Ontario: a five year study.
AB  - Fatal civil aviation crashes in Ontario from 1985 to 1989 were studied. Data
      regarding accident circumstances, injury patterns and medical factors (disease,
      alcohol/drugs) which could have contributed to accident causation was obtained
      from a review of the files of the Chief Coroner for Ontario in Toronto and the
      aviation occurrence reports of the Transportation Safety Board of Canada. Forty
      seven crashes involving mainly general aviation type aircraft but also 2
      gyroplanes, 2 ultralights and a glider were reviewed. About half occurred during
      the cruise phase of the flight. Seventy (40 pilots; 30 passengers) of the 98
      occupants died. The bodies of 68 victims were recovered; 63 were dead at the
      scene and 5 survived up to ten hours after impact. Multiple trauma killed about
      half of all the victims (n = 34); 29% (n = 20) drowned; 16% (n = 11) and 3% (n =
      2) died of head/neck injuries and coronary disease respectively. Neck trauma was
      observed mostly in pilots and was the most frequent major blunt trauma injury in
      drowning victims. Passengers sustained relatively more craniofacial fractures and
      abdominal/retroperitoneal trauma. Pilot error was the most frequent cause of
      crashes (55%; 26/47 impacts) followed by mechanical failure (15%; 7/47) and
      adverse weather/environmental conditions (11%; 5/47). Coronary artery disease
      incapacitated two pilots (4% of crashes) and ethanol intoxication was implicated
      in two other accidents. Other drugs did not appear to be a definite factor in
      accident causation.

PMID- 8871386
TI  - ABO genotyping following a single PCR amplification.
AB  - Using primers designed by Lee and Chang, 200 base-pair (bp) fragment of ABO locus
      was amplified by PCR, which spans the site of the single nucleotide deletion
      associated with O allele. O allele could be identified by Kpn I digestion of the
      PCR product as reported. A and B alleles were also distinguishable by Mae II
      digestion of the product. Thus restriction digestion by Kpn I and Mae II could
      genotype ABO blood group following the single amplification. The nucleotide
      substitution in the 200-bp product between A and B alleles was also found in O
      allele, resulting in 2 different suballeles OA and OG. The single-strand
      conformational polymorphism of the PCR product was also investigated for ABO
      genotyping following the single amplification.

PMID- 8871387
TI  - ABO genotyping of suspects from sperm DNA isolated from postcoital samples in sex
      crimes.
AB  - In sexual assaults against women, one key to identifying the suspect is ABO
      phenotyping or the typing of other polymorphic markers of the seminal fluid in
      the victim's vagina. However, ABO phenotyping is frequently unsuccessful, since
      mixtures of fluids cannot be separated to be subjected to conventional methods
      for the detection of antibody or antigen material. We therefore studied ABO blood
      group genotyping of sperm DNA isolated from contaminating vaginal fluid by the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. Seminal samples of genotypes OO, AO, BO and AB were experimentally mixed
      with vaginal fluid (OO, AO, BO and AB), and were successfully separated and
      genotyped by this method. In practice, we also separated and genotyped the
      seminal DNA of suspects from contaminated postcoital vaginal fluid obtained in 4
      sexual assaults. These forensic samples were easily separated and completely
      genotyped. This reliable ABO genotyping method by PCR-RFLP, using separated sperm
      DNA, should be of value in forensic identification in sexual assaults.

PMID- 8871388
TI  - Gender determination of forensic samples using PCR amplification of ZFX/ZFY gene
      sequences.
AB  - Determining the gender of an evidentiary sample can be an important part of
      casework analyses. Gender information, particularly when combined with
      mitochondrial DNA analysis, can serve to distinguish biological evidence from two
      people who share the same DNA type(s) but differ by sex. When typing sexual
      assault evidence, gender information can serve as confirmation that the "sperm
      fraction" extracted from swabs and stains actually contains male DNA and also as
      an indicator of the amount of male DNA present in the non-sperm fraction. The PCR
      based assay described here relies on amplification of a small, polymorphic region
      of a homologous zinc finger protein locus present on the X and Y chromosomes. The
      gender of the sample donor is determined from the PCR product either by Haelll
      restriction enzyme digestion followed by gel electrophoresis or by hybridization
      to immobilized sequence specific oligonucleotide probes (reverse dot blot). When
      using the reverse dot blot approach, amplification and typing of the gender PCR
      product can be coupled to amplification and typing of the AmpliType HLA DQalpha
      and PM markers. Sensitivity and mixture studies were performed in addition to the
      analysis of casework bloodstains and sexual assault kit samples. Additional
      studies using this gender determination assay are described in the accompanying
      paper.

PMID- 8871389
TI  - Sex determination of dried blood stains using the polymerase chain reaction (PCR)
      with homologous X-Y primers of the zinc finger protein gene.
AB  - The ability to "sex" unknown dried bloodstains is frequently of evidentiary value
      in forensic casework. Chelex-extracted DNA from 115 specimens (105 dried blood
      standards and 10 casework samples) was amplified for specific ZFX and ZFY regions
      of the X and Y chromosomes and subsequent restriction enzyme digestion. The
      polymerase chain reaction (PCR) yielded a 209 base pair (bp) product containing a
      polymorphic position with a Y chromosome portion including an additional Hae III
      restriction site while the X chromosome portion contains only one. The digested
      PCR product was separated by polyacrylamide gel electrophoresis (PAGE) and
      detected by silver staining. Female samples exhibit bands of 172 bp and 37 bp
      only while male samples (XY) exhibit 2 additional bands appearing as an 88/84 bp
      doublet. Initially the 105 known bloodstains were typed according to the
      procedure discussed here and correct gender determination was achieved for all
      samples therefore establishing the reliability of this method. The 10 casework
      samples yielded the expected results as well. This assay demonstrates potential
      in both presumptive and confirmatory capacities.

PMID- 8871390
TI  - Population data on the loci LDLR, GYPA, HBGG, D7S8, and GC in three southwest
      European populations.
AB  - Three Southwest European populations: Galicia (NW Spain), a mixed Spanish
      population from the rest of Spain (outside Galicia), and a population sample from
      the Coimbra area (Centre of Portugal) have been studied for the Low Density
      Lipoprotein Receptor (LDLR), Glycophorin A (GYPA), Hemoglobin G Gammaglobin
      (HBGG), D7S8 and Group Specific Component (GC). The allele and genotype
      frequencies found have been compared with other previously published data. All
      loci meet Hardy-Weinberg expectations in the three sampled populations. There was
      no evidence of association in any of the three population samples, between the
      five loci studied. No significant differences were found with Caucasian
      populations, nevertheless, significant differences were observed between our
      three population studies and the US SW Hispanic and African populations. The
      AmpliType PM DNA test greatly facilitates DNA testing in forensic laboratories,
      providing quick results and a good discrimination power from a single test.

PMID- 8871391
TI  - Identification of a killer by a definitive sneaker pattern and his beating
      instruments by their distinctive patterns.
AB  - A 39-year-old male service station attendant was found murdered on the floor of a
      gasoline service area by a passing motorist who had stopped for gas. The victim
      had been brutally beaten all over his entire body. After carefully examining the
      body and scene and taking selective photographs, special procedures were
      implemented in an attempt to preserve and transport the body without disturbing
      any items of evidence. In addition, specific evidentiary items were noted and
      collected for processing. The victim was meticulously examined externally at
      autopsy using a special protocol to locate clues that might assist in identifying
      a suspect or instrument of injury or death. Patterned impressions and subsequent
      DNA analysis proved successful in identifying the perpetrator of the crime and
      the instruments used in inflicting the beating. It is the purpose of this paper
      to show how a meticulous examination of the body for the presence of patterned
      injuries and critical studies of these patterns and impressions led to the
      identification of a killer and the instruments he used in a brutal beating.

PMID- 8871392
TI  - "Hyperacute" subdural hematoma: CT mimic of recurrent episodes of bleeding in the
      setting of child abuse.
AB  - Mixed density extraaxial hematomae on computed tomography (CT) scanning generally
      represent recurrent episodes of bleeding (chronic subdural hematoma with
      rebleeding). Hyperacute hemorrhages in which the patient is actively bleeding or
      has a coagulopathy have also been described as mixed density. We report a case of
      child abuse in a fourteen month old child who presented with a CT scan showing a
      mixed density subdural hematoma which was originally interpreted as recurrent
      episodes of hemorrhage, but who had evidence of only acute, active bleeding at
      surgery and by histologic examination. There is a proportionally high incidence
      of subdural hematoma in cases of child abuse, due in part to the increased
      susceptibility of the immature brain to trauma. Because the mechanism of injury
      is different for hemorrhage due to hyperacute subdural hematoma (SDH) and that of
      acute bleeding within a chronic SDH, the distinction between these entities has
      potentially important legal implications in cases of suspected child abuse. This
      potential pitfall in interpretation of the CT scan has not to our knowledge been
      reported in the forensic literature.

PMID- 8871393
TI  - Not under the hammer: a revolver suicide.
AB  - A man died from a self-inflicted gunshot wound to the head. The only inconsistent
      finding at the scene was that the single fired cartridge casing in the latched
      revolver cylinder was not under the hammer. This inconsistency is explained by
      the discovery that the revolver cylinder can be hand-indexed in reverse. The
      revelation that the casing does not have to be under the hammer may be a novel
      concept to many investigators.

PMID- 8871394
TI  - Fentanyl patches left on dead bodies -- potential source of drug for abusers.
AB  - We report a fatal case of fentanyl poisoning in which the decedent apparently
      obtained the drug from a used transdermal patch removed from a deceased nursing
      home patient. Fentanyl drug patches, even those previously used, contain a
      potentially lethal amount of this potent narcotic analgesic and provide a source
      of fentanyl for drug abusers. This case demonstrates the importance of proper
      disposal of these drug patches and the need for strict policies and guidelines in
      patient care settings regarding their disposal. Since fentanyl derivatives may
      not be detected on routine toxicologic analysis, specific assays should be
      utilized for the detection of fentanyl in cases of suspected drug overdose.

PMID- 8871395
TI  - Case report: distribution of methamphetamine in a massive fatal ingestion.
AB  - A subject who apparently swallowed a baggie containing "crank" (methamphetamine)
      while being arrested, was admitted to hospital and then experienced a massive
      overdose of the drug. The subject went through a seizure with associated fixed
      dilated pupils, and a depressed pulse and blood pressure. His cardiac and
      respiratory problems could not be stabilized, and he died. Methamphetamine levels
      in central and peripheral blood, liver, bile, vitreous, gastric and urine were
      determined. Blood levels of greater than 60 mg/L, were found together with even
      higher levels in the bile, urine and gastric. These levels are discussed in terms
      of other fatal, non-fatal and recreational methamphetamine use.

PMID- 8871396
TI  - The WW module competes with the SH3 domain?

PMID- 8871397
TI  - Extraribosomal functions of ribosomal proteins.
AB  - The discovery of DNA-binding motifs in ribosomal proteins has led to the
      conjecture that the transition of the ribosome from an RNA to an RNP machine
      occurred by adding pre-existing proteins. Supportive, but circumstantial,
      evidence for the hypothesis is adduced from the finding that many ribosomal
      proteins have a second function apart from the particle. These extraribosomal
      functions are enumerated.

PMID- 8871398
TI  - The origin of the eukaryotic cell.
AB  - Molecular sequence data are beginning to provide important insights into the
      evolutionary origin of eukaryotic cells. Global phylogenies of numerous protein
      sequences indicate that the eukaryotic cell nucleus is a chimera, which has
      received major contributions from both a Gram-negative eubacterium and an
      archaebacterium. Recent studies also indicate that the formation of the nuclear
      envelope and the endoplasmic reticulum was accompanied by duplication of genes
      for the molecular chaperone proteins (e.g. hsp70, hsp90), which facilitate
      protein transport across membranes. Based on these observations, it is suggested
      that the ancestral eukaryotic cell arose by a unique endosymbiotic event
      involving engulfment of an eocyte archaebacterium by a Gram-negative eubacterial
      host.

PMID- 8871399
TI  - Type VI membrane proteins?

PMID- 8871400
TI  - The UBA domain: a sequence motif present in multiple enzyme classes of the
      ubiquitination pathway.

PMID- 8871401
TI  - Iron-sulfur clusters as biosensors of oxidants and iron.
AB  - Iron-sulfur clusters are prosthetic groups commonly found in proteins that
      participate in oxidation-reduction reactions and catalysis. Here, we focus on two
      proteins that contain iron-sulfur clusters, the fumarate nitrate reduction (FNR)
      protein of Escherichia coli and mammalian iron-responsive-element-binding protein
      1 (IRP1), both of which function as direct sensors of oxygen and iron levels.
      Assembly and disassembly of iron-sulfur clusters is the key to sensing in these
      proteins and we speculate that iron-sulfur clusters might be found in other
      regulatory proteins that sense levels of iron and/or oxygen.

PMID- 8871402
TI  - Rho family GTPases: the cytoskeleton and beyond.
AB  - Until recently, members of the Rho family of GTPases were considered primarily to
      be regulators of the distinct structures making up the actin cytoskeleton.
      Several Rho GTPases have now also been shown to play an important role in cell
      transformation. In addition, Cdc42, Rac and Rho activate transcription, providing
      a possible mechanism for their role in growth control.

PMID- 8871403
TI  - p70 S6 kinase: an enigma with variations.
AB  - The S6 ribosomal protein is phosphorylated by p70 S6 kinase (p70S6k). Although
      the cellular role of S6 phosphorylation is still not fully clear, studies on
      p70S6k and its activation have revealed the existence of a novel signalling
      pathway, clues to the mechanism of action of certain immunosuppressants and
      insights into the control of gene expression at the levels of transcription and
      translation.

PMID- 8871405
TI  - DbBrowser: integrated access to databases worldwide.

PMID- 8871406
TI  - Methods and reagents. Eliminating banding artifacts from SDS-PAGE.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methds-reagnts, available on the
      Internet. This month's column discusses how to avoid some artifacts when running
      SDS-polyacrylamide gels, and some other tips for reducing the cost of lab
      supplies are given as well. For details on how to partake in the newsgroup, see
      the accompanying box.

PMID- 8871404
TI  - Structural and mechanistic relationships between nucleic acid polymerases.
AB  - A superfamily of nucleic acid polymerases that includes the pol I and pol alpha
      classes of DNA-directed DNA polymerases, mitochondrial and phage DNA-directed RNA
      polymerases, and most RNA-directed polymerases may be defined on the basis of the
      occurrence of conserved sequence motifs and tertiary structure similarities
      between HIV-1 reverse transcriptase, DNA polymerase I and T7 RNA polymerase.
      Although sequence or structural similarities do not yet justify inclusion of the
      multi-subunit DNA-directed RNA polymerases in this superfamily, mechanistic
      similarities suggest a deep relationship between these and the simpler T7-like
      RNA polymerases.

PMID- 8871407
TI  - Introduction to the special section on attachment and psychopathology: 2.
      Overview of the field of attachment.
AB  - J. Bowlby (1969) proposed that the child's insistence on maintainance of
      proximity to protective (parental) figures was attributable to the activities of
      an attachment behavioral system which regulates primate safety and survival. M.
      D. S. Ainsworth, M. C. Blehar, E. Waters, and S. Wall's (1978) Strange Situation
      procedure later delineated 3 categories of 1-year-old response to brief
      laboratory separations from the parent (secure, avoidant, and resistant), each
      found systematically related to parent-infant interaction, and predictive of
      favorable versus unfavorable sequelae in middle childhood. Recently, a fourth,
      disorganized-disoriented infant Strange Situation category has been identified,
      and infant attachment has been found to predict child narratives. Additionally,
      an Adult Attachment Interview (AAI) and corresponding system of discourse
      analysis has been devised that assesses variations in the ability to maintain
      coherent, collaborative discourse while discussing early relationships and their
      influences. Among parents, differences in patterning of AAI response predict
      corresponding forms of infant Strange Situation behavior, both concurrently and
      before the birth of the first child. Parents who are coherent-collaborative in
      discussing even highly unfavorable histories have infants who are secure. A
      strong majority of clinically distressed individuals are insecure with respect to
      attachment, and special vulnerabilities are appearing in disorganized-disoriented
      children. Relations to behavior genetics, family interaction patterns,
      psychophysiology, and treatment outcome studies are emerging or are anticipated.

PMID- 8871408
TI  - Adolescent attachment and psychopathology.
AB  - The relationships among attachment classification, psychopathology, and
      personality traits were examined in a group of 60 psychiatrically hospitalized
      adolescents. The concordance of attachment classification was examined in 27
      adolescent-mother pairs. Both adolescent and maternal attachment status were
      overwhelmingly insecure and were highly concordant. Adolescents showing a
      dismissing attachment organization were more likely to have a conduct or
      substance abuse disorder, narcissistic or antisocial personality disorder, and
      self-reported narcissistic, antisocial, and paranoid personality traits.
      Adolescents showing a preoccupied attachment organization were more likely to
      have an affective disorder, obsessive-compulsive, histrionic, borderline or
      schizotypal personality disorder, and self-reported avoidant, anxious, and
      dysthymic personality traits. The results support a model of development of
      psychopathology based partially on relational experiences with parents.

PMID- 8871409
TI  - Attachment theory as a framework for understanding sequelae of severe adolescent
      psychopathology: an 11-year follow-up study.
AB  - This study examined long-term sequelae of severe adolescent psychopathology from
      the perspective of adult attachment theory. The study compared 66 upper-middle
      class adolescents who were psychiatrically hospitalized at age 14 for problems
      other than thought or organic disorders, to 76 sociodemographically similar high
      school students. When reinterviewed at age 25, virtually all of the previously
      hospitalized adolescents displayed insecure attachment organizations, in contrast
      to a more typical mixture of security and insecurity in the former high school
      sample. Lack of resolution of previous trauma with attachment figures accounted
      for much of this insecurity. Insecurity in adult attachment organization at age
      25 was also linked to self-reported criminal behavior and use of hard drugs in
      young adulthood. These findings are discussed as reflecting a substantial and
      enduring connection between attachment organization and severe adolescent
      psychopathology and a possible role of attachment organization in mediating some
      of the long-term sequelae of such psychopathology.

PMID- 8871410
TI  - Attachment organization and history of suicidal behavior in clinical adolescents.
AB  - One hundred thirty-three adolescents in psychiatric treatment participated in a
      case-comparison study investigating the association of attachment patterns with a
      history of suicidal behaviors. The comparison group comprised 64 adolescents who
      had never experienced suicidal ideation or behaviors; the case group included 69
      adolescents with histories of suicidal behavior (n = 53) and severe suicidal
      ideation (n =16). Attachment patterns were assessed using the Adult Attachment
      Interview. In accordance with definitions provided in the scoring system, 86% of
      case and 78% of comparison adolescents in psychiatric treatment had experienced
      attachment-related trauma. Lapses in the monitoring of reasoning or discourse
      occurred during the attempted discussion of these events in 73% of adolescents in
      the case group but in only 44% of adolescents in the clinical comparison group (p
      = .002), suggesting that cognitive disorganization may be an important variable
      mediating between traumatic experience and suicidal behavior. Female adolescents
      and older adolescents were significantly more likely than other adolescents to be
      in the case group. Preoccupied attachment, in interaction with unresolved
      disorganized attachment, was associated with the case group, whereas dismissing
      attachment was associated with the comparison group.

PMID- 8871411
TI  - Adult attachment classification and self-reported psychiatric symptomatology as
      assessed by the Minnesota Multiphasic Personality Inventory--2.
AB  - This study examined differences in self-reported psychiatric symptomatology on
      the Minnesota Multiphasic Personality Inventory-2 according to adult attachment
      status on the Adult Attachment Interview in first-time mothers from a high-risk
      poverty sample. Participants reported fairly high levels of symptomatology
      regardless of attachment status. The dismissing adult attachment group reported
      comparatively little psychiatric distress, emphasized independence, and scored
      the lowest on self-reported anxiety. The preoccupied group was highest on a range
      of indices of psychiatric symptoms indicative of self-perceived distress and
      relationship problems. The autonomous group's scores ranged between the scores of
      the other 2 groups on most scales. These different symptom patterns are
      consistent with adult attachment status as an index of self-representation and as
      a set of strategies for processing emotions and thoughts related to distress and
      to attachment relationships.

PMID- 8871412
TI  - Attachment processes in eating disorder and depression.
AB  - This study examines the relationship between attachment strategies and symptom
      reporting among college women. Sixty-one college women were selected who reported
      high or low levels of depressive and eating disorder symptoms. The Adult
      Attachment Interview (AAI) was administered, and interview transcripts were rated
      with the Attachment Interview Q-Sort. The results indicated that women with
      hyperactivating AAI strategies were prone to reporting elevated levels of
      depressive symptoms, whereas women with deactivating strategies were prone to
      reporting elevated levels of eating-disorder symptoms, when depression was
      statistically controlled. These findings support the hypothesis that secondary or
      defensive attachment strategies predispose individuals toward different forms of
      symptom expression.

PMID- 8871413
TI  - Epilogue: bridging the gap between research on attachment and psychopathology.
AB  - Clinicians and researchers are beginning to acknowledge the importance of
      integrating a developmental perspective into the understanding of clinical
      disorders. The application of findings from basic attachment research to this
      understanding of psychopathology is a prototype for interdisciplinary research.
      However, major gaps continue to exist between basic research on attachment
      processes and clinical issues of assessment, classification, and treatment of
      mental disorders from infancy through adolescence. This epilogue highlights the
      importance of more integrative research. As a reflection of growth in this
      direction, National Institute of Mental Health funding patterns are reviewed, and
      promising areas for future research are suggested. The field is well positioned
      for conceptual advancement if more integrative approaches are used.

PMID- 8871414
TI  - A component analysis of cognitive-behavioral treatment for depression.
AB  - The purpose of this study was to provide an experimental test of the theory of
      change put forth by A. T. Beck, A. J. Rush, B. F. Shaw, and G. Emery (1979) to
      explain the efficacy of cognitive-behavioral therapy (CT) for depression. The
      comparison involved randomly assigning 150 outpatients with major depression to a
      treatment focused exclusively on the behavioral activation (BA) component of CT,
      a treatment that included both BA and the teaching of skills to modify automatic
      thoughts (AT), but excluding the components of CT focused on core schema, or the
      full CT treatment. Four experienced cognitive therapists conducted all
      treatments. Despite excellent adherence to treatment protocols by the therapists,
      a clear bias favoring CT, and the competent performance of CT, there was no
      evidence that the complete treatment produced better outcomes, at either the
      termination of acute treatment or the 6-month follow-up, than either component
      treatment. Furthermore, both BA and AT treatments were just as effective as CT at
      altering negative thinking as well as dysfunctional attributional styles.
      Finally, attributional style was highly predictive of both short- and long-term
      outcomes in the BA condition, but not in the CT condition.

PMID- 8871415
TI  - Race and sex differences in the prediction of drug use.
AB  - Efforts to prevent adolescent substance abuse often direct prevention efforts at
      known correlates of substance use. The applicability to minority populations of
      risk factors uncovered for the general population has been questioned, and the
      development of different programs targeting the risk factors most salient for
      different groups has been recommended. Such differentiated programming requires a
      more precise understanding of ethnic differences in the predictors of substance
      use than is now available. This article assesses these differences using data
      from 981 Black and White male and female adolescents and latent variable
      structural equations techniques. No group differences were observed in the
      prediction of past year variety of drug use for 9 of the 12 risk factors
      examined. The predictive validity was higher for Whites than for Blacks for 3
      risk factors. The prediction of frequency of use was weaker for Black women than
      for other groups. The low predictive validity observed for Black women is most
      likely due to the extremely low level of use among this group. The study
      concludes that the measures of risk factors predict substance use for all groups
      examined but that extremely rare behaviors are not well predicted.

PMID- 8871416
TI  - Behavior therapy and the transdermal nicotine patch: effects on cessation
      outcome, affect, and coping.
AB  - The process and outcome of a smoking cessation program using behavior therapy
      alone (BT) or behavior therapy plus the nicotine patch (BTP) was studied in 64
      participants. Participants quit smoking on a target date after a period of ad
      libitum smoking, cognitive-behavior therapy preparing them for cessation, and
      behavioral rehearsal for high-risk situations, including stress management, and
      coping with negative affect. Abstinence was significantly higher for the BTP
      group versus the BT group from the end of behavioral treatment (79% vs. 63%)
      through the 3-month follow-up (p < .01), with the effects weakening at the 6- (p
      = .06) and 12-month marks (p = 38% vs. 22%). More general distress was observed
      among BT versus BTP participants (i.e., increased withdrawal, tension, fatigue,
      and coping frequency with decreased coping effort; coping-to-urge ratio). The
      coping behavior of the BTP group may have been more effective than that of the BT
      group, as indicated by their significantly higher level of self-efficacy.

PMID- 8871417
TI  - Marital conflict and endocrine function: are men really more physiologically
      affected than women?
AB  - This study assessed marital conflict behavior and endocrine function in 90
      newlywed couples. Blood samples acquired hourly from 8:00 a.m. through 10:00 p.m.
      were combined to provide composite daytime values for 3 stress hormones --
      epinephrine (EPI), norepinephrine (NEPI), and cortisol -- and 3 related hormones
      (ACTH, growth hormone, and prolactin). These pooled data provided a window on
      endocrine function in couples for whom the day included a conflict. For wives,
      higher probabilities of husband's withdrawal in response to wife's negative
      behavior were associated with higher NEPI and cortisol levels. In addition,
      higher frequencies of positive behaviors were associated with lower EPI and
      higher prolactin levels among wives. Husbands' endocrine data were not associated
      with behavioral data. These findings are discussed in the context of gender
      models of marital conflict.

PMID- 8871418
TI  - Family treatment of childhood anxiety: a controlled trial.
AB  - A family-based treatment for childhood anxiety was evaluated. Children (n = 79)
      aged 7 to 14 who fulfilled diagnostic criteria for separation anxiety,
      overanxious disorder, or social phobia were randomly allocated to 3 treatment
      conditions: cognitive-behavioral therapy (CBT), CBT plus family management (CBT +
      FAM), and waiting list. The effectiveness of the interventions was evaluated at
      posttreatment and at 6 and 12 months follow-up. The results indicated that across
      treatment conditions, 69.8% of the children no longer fulfilled diagnostic
      criteria for an anxiety disorder, compared with 26% of the waiting-list children.
      At the 12-month follow-up, 70.3% of the children in the CBT group and 95.6% of
      the children in the CBT + FAM group did not meet criteria. Comparisons of
      children receiving CBT with those receiving CBT + FAM on self-report measures and
      clinician ratings indicated added benefits from CBT + FAM treatment. Age and
      gender interacted with treatment condition, with younger children and female
      participants responding better to the CBT + FAM condition.

PMID- 8871419
TI  - On criterion weighting in the DSM-IV.
AB  - Differential weighting of illness signs and symptoms has surfaced recurrently in
      psychiatric nosology. Six alternately weighted algorithms for diagnosing alcohol
      dependence in accordance with the Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994), based on
      statistical, unit, rational and random criterion weighting systems, were used to
      predict an array of concurrent validators and 6-month drinking outcomes in a
      regional clinical sample of 365 participants. Comparable predictive efficiency
      across all algorithms, including the randomly weighted versus statistical best
      fit model, was observed. Further analyses and geometric modeling suggested that
      this was due to the extremely high internal consistency of the DSM-IV criteria.
      An alternative strategy that favors factorially complex, less homogeneous
      criteria was used to develop an experimental DSM-IV algorithm from an array of 39
      candidate criteria. This algorithm had extremely low internal consistency, high
      difficulty, and complex factor loadings. Differential weighting of its criteria
      produced a good range of efficiencies, predictive power for rational models
      exceeding the random weight model, and a best-fit algorithm with substantial
      surplus predictive power. These results illustrate an emerging conflict in
      nosology between 2 opposing trends: a press for the promulgation of criterion
      arrays with high internal consistency and a clear desire to assign some criteria
      extra weight for prognosis or decision making. Both cannot be had in the same
      algorithm. An alternative approach emphasizing diagnostic criteria with complex
      structures can satisfy the multiple demands of brevity, validity, and weighting
      performance.

PMID- 8871420
TI  - Disruptive behavior disorder and intergenerational attachment patterns: a
      comparison of clinic-referred and normally functioning preschoolers and their
      mothers.
AB  - This study examined linkages between child disruptive behavior disorder (DBD),
      quality of mother-child interactions, and mothers' recollections of and attitudes
      toward their own parents. Twenty-five preschool boys referred to a psychiatric
      clinic were matched with normally functioning boys. Mothers and sons were
      videotaped during a separation-reunion sequence, the Adult Attachment Interview
      was administered to mothers, and mothers completed questionnaires assessing
      family environment. Mothers of boys with DBD described relationships with their
      own parents less coherently than comparison mothers did, indicating less secure
      representations of attachment. Maternal and child attachment classifications were
      concordant. Log-linear analyses suggested that the influence of maternal
      representation of attachment on disruptive behavior problems was secondary to the
      quality of mother-child interaction.

PMID- 8871421
TI  - First lapses to smoking: within-subjects analysis of real-time reports.
AB  - Studies of smoking relapse and temptation episodes have relied on retrospective
      recall and confounded between- and within-subject variability. Real-time data on
      temptations and lapses to smoke were gathered using palm-top computers. We made
      within-subject comparisons of the initial lapse, a temptation episode, and base
      rate data obtained through randomly scheduled assessments. Negative affect
      discriminated all three situations, with lapses worse than temptations, and
      temptations worse than random situations. Participants attributed lapses to
      negative mood and smoking cues, whereas temptations were more often attributed to
      behavioral transitions. Participants were 12 times more likely to report coping
      in temptations than in lapses. However, only cognitive (vs. behavioral) coping
      strategies were effective. Lapses (vs. the other situations) were more likely to
      occur when smoking was permitted, when cigarettes were easily available, and in
      the presence of other smokers. The results have clinical implications, and the
      computerized monitoring methods may be applicable to an array of clinical
      research problems.

PMID- 8871422
TI  - Health status and satisfaction with health care: results from the medical
      outcomes study.
AB  - Relations between self-assessed health status and satisfaction with health care
      were examined using 2 waves of data obtained from participants in the Medical
      Outcomes Study. Using a multisample covariance modeling framework, separate
      models were examined for patients with significant symptoms of depression (n =
      417) and patients with chronic physical health conditions (n = 535). The pattern
      of findings was essentially identical for both patient subgroups. General
      satisfaction with care was cross-sectionally associated with mental -- but not
      physical -- health status. In addition, significant cross-lagged effects were
      found linking baseline satisfaction with care to subsequent mental health and
      baseline mental health to subsequent satisfaction with care. By contrast, no
      cross-lagged directional effects linking satisfaction with care and physical
      health status were identified. Finally, no evidence was found that satisfaction
      with specific aspects of health care contributed independently to either mental
      or physical health.

PMID- 8871423
TI  - The New Hampshire study of supported employment for people with severe mental
      illness.
AB  - This study compared supported employment services in 2 contrasting programs: (a)
      Group Skills Training, a professional rehabilitation agency outside of the mental
      health center that provided pre-employment skills training and support in
      obtaining and maintaining jobs, or (b) the Individual Placement and Support (IPS)
      model, which integrated clinical and vocational services within the mental health
      center. People with severe mental disorders who expressed interest in competitive
      employment (N = 143) were randomly assigned to 1 of these 2 programs. Results
      showed that clients in the IPS program were more likely to be competitively
      employed throughout most of the 18-month follow-up. Among those who obtained
      jobs, there were few group differences, although workers in the IPS program did
      work more total hours and earn more total wages during the 18-month follow-up.
      There were no group differences on nonvocational outcomes.

PMID- 8871424
TI  - Weight cycling, psychological health, and binge eating in obese women.
AB  - This study examined the relationship between weight cycling and psychological
      health in 120 obese women. Weight cycling was defined in 2 ways by retrospective
      self-report: total lifetime weight loss and total number of weight cycles > or =
      20 lbs (> or = 9.07 kg). Psychological self-report measures assessed psychiatric
      symptoms, eating behavior, mood, stress, and perceptions of physical health. Of
      the 52 associations between weight cycling and psychological parameters, 8 were
      significant, with the most consistent association being between weight cycling
      and binge eating. Binge eating was also strongly associated with psychological
      distress, as found in previous studies. After adjusting for binge eating,
      however, weight cycling was independently related to only one of the
      psychological measures: perceived physical health.

PMID- 8871425
TI  - Effects of stress inoculation training on athletes' postsurgical pain and
      rehabilitation after orthopedic injury.
AB  - The efficacy of a cognitive-behavioral intervention (stress inoculation training;
      SIT) for postsurgical anxiety, pain, and physical rehabilitation in injured
      athletes was tested. Sixty male athletes who underwent arthroscopic surgery for
      miniscus injury in 1 knee were randomly assigned to either treatment (SIT and
      physical therapy) or control (physical therapy only) conditions. Results showed
      that participants in the treatment group demonstrated significantly less
      postsurgical pain and anxiety during the rehabilitation process, compared with
      controls. Additionally, treated participants required fewer days to return to
      criterion physical functioning, compared with nontreated participants.

PMID- 8871427
TI  - Behavioral components of marital satisfaction: an individualized assessment
      approach.
AB  - This study examined the extent to which spousal behaviors, obtained through a
      daily checklist of marital activities individualized along an importance
      dimension, related to global and daily marital satisfaction. Eighty-two marital
      couples completed daily checklists of spousal behaviors for 7 days using either
      an individualized or a standardized assessment method. The results demonstrated
      that the individualized measures of daily behavioral events were significantly
      related to global and daily measures of marital satisfaction and discriminated
      distressed from nondistressed spouses. Although the individualized method did not
      correlate with marital satisfaction to a significantly greater degree than the
      standardized method, the individualized assessment approach provides a valid,
      viable, and cost-effective alternative for assessing daily spousal events that
      relate to marital satisfaction.

PMID- 8871426
TI  - Dynamic change in psychotherapy: mastery of interpersonal conflicts.
AB  - This study investigated the relationship between the mastery of maladaptive
      interpersonal patterns (assessed from narratives told during psychotherapy) and
      outcome of psychotherapy. Transcripts from the psychodynamic psychotherapy of 41
      patients were scored using a content analysis mastery scale. Changes in mastery
      level over the course of therapy were significantly related to changes in
      observer and therapist ratings. In addition, the patients' own judgments of
      changes in their symptoms and main problems paralleled changes in the mastery of
      interpersonal conflicts found in their narratives. These results are consistent
      with the proposition that symptoms abate with the mastery of core interpersonal
      conflicts.

PMID- 8871429
TI  - Practice-based research--the time has come!

PMID- 8871428
TI  - Cascading toward divorce: the roles of marital and child factors.
AB  - This longitudinal study examined the role of marital and child factors in
      predicting divorce potential and actual divorce occurrence. Participants included
      140 young adolescents (73 girls, 67 boys; mean age = 13 years 2 months) and their
      parents. Child-related (number of children in the family, the presence of a male
      child in the family, and the adolescent's level of anxiety-withdrawal and conduct
      disorder problems) and intramarital (marital satisfaction and, for some analyses,
      divorce potential) factors served as predictors. For both wife and husband data,
      lower levels of marital satisfaction predicted higher current levels of divorce
      potential, and, in turn, divorce potential predicted greater likelihood for
      divorce up to 7 years later. No child-related variables predicted divorce
      potential or divorce occurrence.

PMID- 8871430
TI  - Telephone follow-up after discharge from the hospital: does it make a difference?
AB  - Two systems of telephone follow-up of discharged patients were compared in this 3
      month study. All medical and surgical patients on five nursing units of one acute
      care institution were included, yielding a sample of over 1,400 patients. One
      group of patients was called 2 to 3 days after discharge; another group received
      a brochure describing a nurse-run telephone service they could call. A third
      group of patients received no intervention. More than 90% of patients who were
      called had questions about self-care and recovery at home. Only nine patients
      initiated calls to the nurse telephone service. The three groups did not differ
      in patient satisfaction with health education or readmission rates within 30 days
      of discharge. This study suggests that patients have continued health education
      needs after discharge but are unlikely to actively seek needed information from a
      hospital-based telephone service.

PMID- 8871431
TI  - Relationships among illness uncertainty, stress, coping, and emotional well-being
      at entry into a clinical drug trial.
AB  - The purpose of this cross-sectional study was to examine the relationships among
      illness uncertainty, stress, coping, and emotional well-being at the time of
      entry into a clinical drug trial. Hopefulness and mood state were included as
      indicators of emotional well-being. The sample included 59 clients who
      participated in a 2-year trial using methotrexate for progressive multiple
      sclerosis. Results indicated that ambulation status, education, perceived stress,
      and illness uncertainty were the best correlates of emotional well-being. The
      results suggest that clients entering a drug trial with high levels of illness
      uncertainty and stress are likely to experience mood disturbances and feel less
      hopeful about treatment effectiveness. This information may be used as a
      foundation for developing nursing interventions designed to foster emotional well
      being at the time of entry into drug trials.

PMID- 8871432
TI  - Social support and physical health in the rural elderly.
AB  - The purpose of this study was to describe the social support networks, level of
      social support, and perceived physical health of older rural adults. Eighty-two
      randomly selected subjects over 65 years of age participated. Data were collected
      using the Personal Resource Questionnaire (PRQ85) and a single-item measure to
      assess health. Findings suggest that older rural adults have few people in their
      social support networks, decreased levels of support, and poor health. Because
      social support has a positive influence on health, nurses need to find ways to
      increase the level of support in the rural aged.

PMID- 8871433
TI  - Positioning intervention to minimize fatigue in breastfeeding women.
AB  - Nursing interventions to enhance breastfeeding affect the health of mothers and
      babies. Fatigue may interfere with breastfeeding, so interventions minimizing
      fatigue are important. This repeated measures study of 20 postpartum women
      investigated the relative efficacy of one intervention, promoting use of the side
      lying position. Using the Modified Fatigue Symptoms Checklist, fatigue was
      measured after breastfeeding in two positions. In mothers who had vaginal
      deliveries (n = 14), significantly less fatigue was reported following nursing in
      the side-lying versus the sitting position. Instruction regarding restfulness of
      the side-lying position should be considered as part of routine postpartum or
      home health nursing care.

PMID- 8871434
TI  - Inpatient self-management of bipolar disorder.
AB  - As part of a grounded theory study of the self-management informational needs and
      activities of inpatients with bipolar disorder, an analysis was conducted to
      describe how hospitalized people with bipolar disorder manage their illness.
      Thirty-three people participated in semistructured, audiorecorded interviews that
      included questions about their self-management. Findings related to three areas:
      (a) factors that affect self-management, (b) patient-initiated self-management
      interventions, and (c) information believed by the participants to be important
      for other people with the disorder. Advances in the understanding of the self
      management of people with bipolar disorder are pivotal to the development of
      strategies that may reduce, and perhaps one day prevent, relapse.

PMID- 8871435
TI  - Predictive validity of the Braden Scale and nurse perception in identifying
      pressure ulcer risk.
AB  - Before the implementation of the Braden Scale, an institutional study was
      conducted to determine the cut-off point at which patients would be at risk for
      developing a pressure ulcer. Nurses' perception of patient risk for pressure
      ulcer development also was compared with the Braden Scale. One hundred and three
      subjects hospitalized for a minimum of 7 days and randomly selected from routine
      hospital admissions were rated with the Braden Scale, and skin assessments were
      made three times per week for up to 2 weeks starting 24 to 48 hours after
      admission. In addition, bedside nurses were asked to use clinical judgment to
      identify subjects at risk for pressure ulcer development. Twenty-nine subjects
      developed pressure ulcers. Nurse's judgements of pressure ulcer risk were not
      significant in predicting pressure ulcer positive or negative status. Results of
      the t test demonstrated the Braden Scale score is the most highly significant
      finding (p = .0038) to predict pressure ulcer positive and pressure ulcer
      negative groups. For this study, the Braden Scale cut-off point was set at 17
      with a sensitivity of .59 and a specificity of .59. Clinical implementation of
      the Braden Scale must be combined with frequent and thorough skin assessment
      practices because some patients will develop pressure ulcers even though the tool
      does not predict the patients to be at risk.

PMID- 8871436
TI  - Adjustment of women with systemic lupus erythematosus.

PMID- 8871437
TI  - The values history as a nursing intervention to encourage use of advance
      directives among older adults.

PMID- 8871438
TI  - Poster etiquette.

PMID- 8871439
TI  - Environment and health 1, overview and main European issues.
AB  - The environment can have an important influence on health. The European
      Environment Agency (EEA) and the WHO European Centre for Environment and Health
      (ECEH) developed this publication as a joint effort to draw attention to some
      environmental issues that have a significant impact on the health of the people
      of Europe. It represents the logical complement and continuation of their
      cooperative work. Pooling the immense amounts of data that they have gathered,
      EEA and ECEH have distilled the resulting knowledge into a brief discussion of
      the contribution of environmental factors to the main causes of death in Europe,
      and an examination of three particularly significant issues. These issues meet
      important criteria. Each is a widespread problem that causes significant damage
      to the health of many people throughout Europe, and all are amenable to
      coordinated action that would result in both improved environmental quality and
      health benefits within a short time. Delaying this action would increase the
      damage and make these problems harder to solve in the future. This book not only
      identifies these issues -- air pollution with suspended particles, the
      microbiological contamination of drinking-water and road traffic accidents -- and
      sketches the harm that they do, but lists goals and strategies for action now.
      This book offers useful reading for everyone interested in a healthy environment,
      health protection and sustainable development. It offers practical suggestions
      for action to make Europe a safer and healthier place to live, for today's
      Europeans and tomorrow's.

PMID- 8871440
TI  - Review article: the medical management of Crohn's disease.
AB  - The choice of medical therapies for Crohn's disease continues to grow. Although
      our understanding of the mechanisms of the disease is incomplete, increasing
      knowledge of the pathogenesis of inflammation in general and Crohn's disease in
      particular allows targeting of therapies at various points in the
      immunoinflammatory cascade. In addition, the division of Crohn's disease into
      subtypes by location, aggressiveness, and the presence or absence of perianal and
      fistulizing disease allows the tailoring of medical therapy to the individual
      patient. For those patients with moderate to severe symptoms or frequent flares
      of disease activity, and those who have required surgical resection, maintenance
      therapy can substantially reduce the rate of recurrence. Despite these advances,
      available medical therapies for Crohn's disease remain imperfect, as evidenced by
      their sometimes substantial toxicities and the continued frequent need for
      surgery.

PMID- 8871441
TI  - Review article: drug-induced pancreatitis.
AB  - Drugs are a relatively uncommon cause of pancreatitis in adult patients, but
      should be considered when other reasonable causes of pancreatitis are not
      present. A wide variety of drugs have been reported to cause pancreatitis. Drug
      induced pancreatitis is almost always acute and may be mild to fatal in severity.
      Definite proof that a drug causes pancreatitis requires that pancreatitis
      develops during treatment with the drug, that other likely causes of pancreatitis
      are not present, that pancreatitis resolves upon discontinuing the drug, and that
      pancreatitis usually recurs upon readministration of the drug. For ethical
      reasons, rechallenge with the suspect drug can be done only if the drug is
      necessary to treat a serious condition; thus this highly convincing piece of
      evidence relating the drug to pancreatitis may not be available. Information
      about drug-related pancreatitis is often not readily available, particularly for
      newer drugs. Clinicians should consider obtaining information directly from
      regulatory agencies and manufacturers as well as the literature.

PMID- 8871442
TI  - Review article: refractory distal colitis -- explanations and options.
AB  - Distal colitis refractory to standard therapy is a complex and challenging
      problem. Physiological differences between the right and left colon may be
      exploited for maximum therapeutic benefit. Over-reliance on oral therapy should
      be seen as one of the reasons for treatment failure and delivery systems should
      target therapy to the distribution of the disease in doses proven to be
      therapeutically beneficial. The clinician should also be cognizant of potential
      adverse effects of standard therapies, particularly colitis due to mesalazine,
      which may mimic worsening disease. Numerous endogenous and exogenous factors that
      may exacerbate the underlying inflammatory bowel disease are discussed. This
      review explores the potential mechanisms why distal colitis may be refractory to
      therapy and addresses newer therapies that, while still in the investigatory
      stages, offer hope for a widening armamentarium of therapeutic modalities.

PMID- 8871443
TI  - Conference report: duodenal ulcer trials reported at the European Helicobacter
      pylori Study Group, Edinburgh 1995.
AB  - The abstracts from the 8th International Workshop on Gastro-duodenal Pathology
      and Helicobacter pylori held in Edinburgh, 7-9 July 1995, are published in Gut
      1995; 37 (Suppl. 7). I was privileged to act as reporter to the Plenary Workshop
      on Duodenal Ulcer Trials chaired by Prof. Seppala. Prof. Roy Pounder and I felt
      that in such a fast moving field as Helicobacter pylori there would be some merit
      in briefly reviewing the eight excellent papers presented at the Workshop. The
      main reason for this being that six of the presentations were well conducted
      randomized prospective clinical trials of H. pylori eradication therapy and the
      other two had important clinical messages.

PMID- 8871444
TI  - Clinical economics review: gastroenterology.
AB  - In the prevailing climate of cost containment, doctors are increasingly expected
      to consider the economic consequences of treatment choices. Clinical (or medical)
      economics attempts to apply economic principles to the description and analysis
      of the costs of medical interventions, so as to identify how best to spend scarce
      health care resources. Such economic evaluations may assess the overall financial
      burden of a disease to society as a whole (macro-economics), or attempt to
      compare alternative treatment strategies for a specific clinical situation (micro
      economics). In addition to expenditure on drugs and investigations (direct
      medical costs), economic studies may consider a variety of other costs. These
      include direct costs borne by patients (e.g. prescription charges, travel, food),
      indirect costs to society owing to lost productivity (resulting from morbidity or
      premature mortality) and even intangible costs which assign a monetary value to
      outcomes of disease such as pain, distress and anxiety. Four main types of
      economic analysis are in current use. Cost-minimization analysis attempts to
      identify the least expensive option in situations where there are a range of
      equally effective treatments for a given clinical condition, whereas cost
      effectiveness analysis allows management strategies differing both in cost and
      efficacy to be compared. The cost-effectiveness of health care programmes
      targeting different disease states may also be compared using cost-utility
      analysis, in which health benefits are translated into a common utility-based
      unit of outcome, such as the Quality Adjusted Life Year (QALY). Cost-benefit
      analysis attempts to quantify health outcomes in monetary terms, so that the net
      result provides an assessment of value-for-money of health interventions.
      Gastrointestinal disorders are amongst the commonest of complaints, and
      considerable health care resources are consumed in treatment. Issues of cost
      effectiveness are likely to assume increasing importance in gastroenterology
      because of the ever expanding range of drug choice, the increasing number of high
      cost treatments and the development of new therapeutic interventions.

PMID- 8871445
TI  - A prospective study of the effectiveness of low dose omeprazole as initial
      therapy in Zollinger-Ellison syndrome.
AB  - BACKGROUND: The proton pump inhibitors (omeprazole and lansoprazole) are the
      drugs of choice for the medical management of gastric acid hypersecretion in
      Zollinger-Ellison syndrome (ZES). These drugs are safe for long-term therapy but
      are acid-labile and high doses are expensive. The recommended starting dose of
      omeprazole is 60 mg/day. However, it has been shown in recent studies that the
      maintenance dose of omeprazole could be safely reduced to 20 mg once or twice a
      day in more than two-thirds of patients with ZES. The purpose of this study is to
      determine if an initial starting dose of omeprazole 20 mg/day is safe and
      effective in patients with ZES. METHODS: Forty-nine consecutive patients with ZES
      being treated with ranitidine for at least 2 weeks were admitted to the NIH.
      Omeprazole 20 mg was started on day 1 of the admission and ranitidine
      discontinued 4 h after the first dose. Gastric acid output was measured for 1 h
      prior to the next omeprazole dose on day 2, then on day 3 if the value was > 10
      mmol/h on the previous day. If acid-peptic symptoms developed or the gastric acid
      output remained > 10 mmol/h on day 3, the patient was considered to have failed
      omeprazole 20 mg/day initial therapy and the dose titrated daily to achieve
      adequate control of acid-peptic symptoms and gastric secretion. RESULTS: In 33 of
      the 49 patients (68%) omeprazole 20 mg/day was successful as initial therapy.
      Sixteen patients (32%) failed this initial omeprazole dose (eight patients owing
      to persistent peptic symptoms and eight patients owing to inadequate acid
      control). The final daily omeprazole dose required in these patients was 40 mg in
      eight patients (16%), 60 mg in one patient (2%) and 80 mg in seven patients
      (14%). Basal acid output (BAO) was the only clinical or laboratory feature that
      was significantly different between the two groups in which low dose initial
      omeprazole therapy was or was not successful; all patients with basal acid output
      < 20 mmol/h had a successful outcome. CONCLUSIONS: Because of the need to rapidly
      control gastric acid hypersecretion owing to the high risk of complications from
      peptic ulcer disease, patients with ZES should continue to be started on
      omeprazole 60 mg/day and the dose adjusted by acute titration methods as is
      currently recommended. After a maintenance dose is established, attempts should
      be undertaken to reduce the dose to 20 mg/ day once or twice a day. Only the
      minority of patients with ZES in whom basal acid output is known to be < 20
      mmol/h (20% of patients) should be started on a low initial omeprazole dose.

PMID- 8871446
TI  - Ropivacaine gel in active distal ulcerative colitis and proctitis -- a
      pharmacokinetic and exploratory clinical study.
AB  - BACKGROUND: Local anaesthetics have anti-inflammatory effects as indicated by
      preclinical and explorative clinical data. OBJECTIVE: To investigate the
      pharmacokinetics, tolerability and clinical efficacy of the new local anaesthetic
      ropivacaine in active distal ulcerative colitis. METHODS: Twelve patients were
      openly given 200 mg ropivacaine gel rectally twice daily for 2 weeks in this open
      study. RESULTS: Mean peak total plasma concentrations, Cmax, were 1.37, 1.26,
      1.03 and 0.99 mg/L on treatment days 1, 3, 7 and 14. The mean unbound plasma
      concentrations at Cmax were 0.071, 0.058, 0.050 and 0.045 mg/L. The decrease in
      Cmax (P < 0.01) as well as in the area under the plasma concentration-time curve,
      AUC (P < 0.01), may be due to a decreased absorption but an increased metabolism
      cannot be excluded. The median time of Cmax was around 2 h and the mean terminal
      half-life was around 2.7 h. Mucosal inflammation assessed endoscopically at the
      most severely affected site decreased after 2 weeks of treatment (P < 0.01;
      blinded) and there was also a trend towards histological improvement (P = 0.06).
      Clinical symptoms, including total number of stools, blood in stools and
      diarrhoea increased (P < 0.05) during the study. The treatment was, in general,
      well tolerated with few gastrointestinal complaints and there were no unequivocal
      signs of systemic effects. CONCLUSIONS: Ropivacaine given rectally as a gel, 200
      mg twice daily does not accumulate over a 2-week treatment period and carries a
      low risk for systemic adverse effects. The results suggest a therapeutic efficacy
      in active distal ulcerative colitis.

PMID- 8871447
TI  - A survey of dyspepsia in Great Britain.
AB  - OBJECTIVES: To determine the prevalence of dyspepsia in the adult population of
      Great Britain and to describe the clinical features, treatment, effect of
      dyspepsia on daily lives and perceptions of peptic ulcer disease. DESIGN: Cross
      sectional survey of the adult population using structured questionnaires.
      SETTING: Subjects interviewed at more than 150 sampling points in England,
      Scotland and Wales in November 1994. SUBJECTS: A representative sample of the
      adult population comprising 2112 subjects, aged 16 years or more. MAIN OUTCOME
      MEASURES: The prevalence of dyspepsia in the adult population and the frequency
      of various characteristics in dyspeptic subjects. RESULTS: The prevalence of
      dyspepsia was 40%. Upper abdominal pain and heartburn were the most frequently
      reported symptoms. Solitary symptoms were uncommon and there was frequent overlap
      between 'ulcer-like' and 'reflux-like' dyspepsia. Forty-six per cent of dyspeptic
      subjects reported moderate or severe symptoms. More than half of symptomatic
      subjects took medication and 22% had visited their GP during the previous year.
      Overall, 2% of the survey sample had been absent from work due to dyspepsia.
      Awareness of the factors precipitating or aggravating peptic ulcer disease was
      poor, particularly in relation to anti-inflammatory drugs. CONCLUSIONS: The
      present study emphasizes the magnitude of the problem of dyspepsia in the adult
      population of Great Britain. The survey also shows that the public in general,
      and patients in particular, require more information if they are to avoid factors
      known to damage the upper alimentary tract.

PMID- 8871448
TI  - Symptomatology, quality of life and economic features of irritable bowel syndrome
      -the effect of hypnotherapy.
AB  - AIMS: The purposes of this study were to quantify the effects of severe irritable
      bowel syndrome on quality of life and economic functioning, and to assess the
      impact of hypnotherapy on these features. METHODS: A validated quality of life
      questionnaire including questions on symptoms, employment and health seeking
      behaviour was administered to 25 patients treated with hypnotherapy (aged 25-55
      years; four male) and to 25 control irritable bowel syndrome patients of
      comparable severity (aged 21-58 years; two male). Visual analogue scales were
      used and scores derived to assess the patients' symptoms and satisfaction with
      each aspect of life. RESULTS: Patients treated with hypnotherapy reported less
      severe abdominal pain (P < 0.0001), bloating (P < 0.02), bowel habit (P <
      0.0001), nausea (P < 0.05), flatulence (P < 0.05), urinary symptoms (P < 0.01),
      lethargy (P < 0.01), backache (P = 0.05) and dyspareunia (P = 0.05) compared with
      control patients. Quality of life, such as psychic well being (P < 0.0001), mood
      (P < 0.001), locus of control (P < 0.05), physical well being (P < 0.001) and
      work attitude (P < 0.001) were also favourably influenced by hypnotherapy. For
      those patients in employment, more of the controls were likely to take time off
      work (79% vs. 32%; p = 0.02) and visit their general practitioner ( 58% vs. 21%;
      P = 0.056) than those treated with hypnotherapy. Three of four hypnotherapy
      patients out of work prior to treatment resumed employment compared with none of
      the six in the control group. CONCLUSION: This study has shown that in addition
      to relieving the symptoms of irritable bowel syndrome, hypnotherapy profoundly
      improves the patients' quality of life and reduces absenteeism from work. It
      therefore appears that, despite being relatively expensive to provide, it could
      well be a good long-term investment.

PMID- 8871449
TI  - Prevention of water immersion stress-induced gastric lesions through the
      enhancement of nitric oxide synthase activity in rats.
AB  - BACKGROUND: Gastric mucosal microcirculation is an important factor in the
      protection of gastric mucosa, and nitric oxide (NO) plays a crucial role in the
      regulation of regional blood flow. This study was designed to evaluate the effect
      of cetraxate, an anti-ulcer drug, on water immersion stress-induced gastric
      lesions in relation to the changes in NO synthase activity. METHODS: Gastric
      lesions were induced in rats by water immersion stress. The effects of cetraxate
      on NO synthase activity with or without stress was determined enzymatically.
      Changes in gastric mucosal prostaglandin (PG) contents with or without stress
      were also determined using high-performance liquid chromatography. Gastric
      mucosal blood flow was measured by hydrogen gas clearance technique. RESULTS:
      Water immersion stress-induced gastric lesions. Cetraxate significantly mitigated
      the lesions but N(G)-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO
      synthase, exacerbated the lesions. The favourable effect of cetraxate was
      remarkably diminished by administration of L-NMMA. NO synthase activity decreased
      significantly by 6 h after stress. Cetraxate treatment increased NO synthase
      activity throughout the experiment in rats with or without stress treatment.
      Water immersion stress decreased all PGs detected, i.e. 6-keto-PGF1alpha,
      PGF2alpha, PGE2 and PGD2. Cetraxate prevented stress-induced decreases in PG
      contents. L-NMMA showed no significant effect on PG contents. Cetraxate increased
      gastric mucosal blood flow significantly and L-NMMA cancelled out cetraxate
      induced increase in blood flow. CONCLUSIONS: The pharmacological efficacy of anti
      ulcer drugs such as cetraxate might be attributable to the enhancement of NO
      synthase activity resulting in an increase in gastric mucosal blood flow.

PMID- 8871450
TI  - The effect of omeprazole on gastric juice viscosity, pH and bacterial counts.
AB  - BACKGROUND: In vitro studies have shown that pH is an important determinant of
      mucus structure and function, but the relationship in vivo is unclear. Omeprazole
      increases intragastric pH and also allows bacterial overgrowth. In this study we
      have assessed the effect of omeprazole on gastric juice viscosity and examined
      the influence of pH and bacterial overgrowth on the resulting change. METHODS:
      Gastric juice specific viscosity, pH and total bacterial counts were measured in
      nine healthy male volunteers before and after omeprazole 20 mg twice daily for 1
      week. The effect of incubation at pH 2 and 7 was also determined. Viscosity
      changes were compared with changes in pH and bacterial counts. RESULTS: Mean
      viscosity fell (P < 0.05) following treatment, though there was a wide range in
      viscosity both before and after treatment. The decrease was reproduced by
      incubation of pre-treatment juice at pH 7 but not pH 2. The fall in viscosity was
      correlated (P < 0.05) with change pH. CONCLUSION: Omeprazole decreases gastric
      juice, and hence gastric mucus, viscosity by increasing intragastric pH. This
      could be important if it allows improved penetration of antimicrobials to
      Helicobacter pylori within the mucus layer.

PMID- 8871451
TI  - The effects of omeprazole and famotidine on mucin and PGE2 release in the rat
      stomach.
AB  - BACKGROUND: Gastric antisecretory agents may inhibit the synthesis or secretion
      of gastric mucin during acid suppression, which would interfere with mucosal
      protection and limit the efficacy of the agents. METHODS: Rats were dosed with
      famotidine, omeprazole, or buffer control for 4 weeks. Mucin synthesis, mucin
      histochemistry, mucin carbohydrate composition and prostaglandin E2 (PGE2)
      release were measured during and after drug treatment. RESULTS: PGE2 release was
      maximally inhibited after 2 weeks of omeprazole or 4 weeks of famotidine. Total
      glycoprotein synthesis was inhibited at all times by omeprazole, but only after
      the cessation of dosing with famotidine. Sulphated glycoprotein synthesis was
      inhibited by both drugs at 2 weeks. PGE2 release and sulphated glycoprotein
      synthesis were restored to control values or more by the 5th day after the end of
      dosing, at which time total glycoprotein synthesis was significantly suppressed
      in both groups. Histologically, a reduction of PAS-positive surface mucus was
      observed after 2 weeks of dosing in both groups. Both famotidine and omeprazole
      reduced the sialic acid content during and after treatment. CONCLUSIONS: These
      results suggest that long-term anti-secretory therapy also affects the production
      of factors involved in primary gastric mucosal defence, which should be
      considered in the assessment of response to treatment in clinical trials.

PMID- 8871452
TI  - Metronidazole, ranitidine and clarithromycin combination for treatment of
      Helicobacter pylori infection (modified Bazzoli's triple therapy).
AB  - BACKGROUND: Multi-drug regimens are generally required to reliably cure
      Helicobacter pylori infection. Metronidazole, clarithromycin and omeprazole has
      proven to be an effective combination therapy with a cure rate of 90% or greater.
      METHODS: We evaluated a 14-day combination regimen for H.pylori infection
      consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and
      ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was
      continued for an additional 4 weeks. H. pylori status was determined by rapid
      urease testing, histopathology using the Genta stain, and by culture at entry and
      4 weeks after completing antimicrobial therapy. RESULTS: Twenty-seven patients
      with documented peptic ulcer disease and H. pylori infection were treated. Five
      had previously failed macrolide-based antimicrobial therapy; none had received
      metronidazole. All ulcers were healed at week 6 except one patient taking
      naproxen; his H. pylori infection was cured. Overall, H. pylori infection was
      cured in 78% (95% CI = 58-91%). In patients with clarithromycin-sensitive
      isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66-97%); only one of four
      patients (25%) with clarithromycin-resistant isolates was cured. In contrast,
      four of five patients with metronidazole-resistant isolates were cured (80%). In
      patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18
      (89%, 95% C.I. = 65-99%). Mild side effects were reported by 27%, including
      diarrhoea and altered taste. Compliance averaged 98%. CONCLUSION: These results
      suggest that the combination of metronidazole, ranitidine and clarithromycin
      results in high cure rates in patients with clarithromycin-sensitive isolates.
      Omeprazole may not be required for Bazzoli's triple therapy; and large
      multicentre comparative trials are indicated.

PMID- 8871453
TI  - Sepsis, septicaemia, sepsis syndrome, and septic shock: the correct definition
      and use.

PMID- 8871454
TI  - Impaired glucose tolerance and unidentified diabetes.
AB  - The epidemiology of impaired glucose tolerance and undiagnosed non-insulin
      dependent diabetes mellitus is reviewed and the implications for screening
      strategies discussed.

PMID- 8871455
TI  - Cerebral venous thrombosis.
AB  - Cerebral venous thrombosis is a treatable and under-recognised cause of a benign
      intracranial hypertension syndrome, and may also cause focal signs, seizures, and
      depression of consciousness.

PMID- 8871456
TI  - A reader's guide to the evaluation of screening studies.
AB  - In this article we will review how a reader should evaluate a screening study. A
      clinical problem involving screening mammography is presented. We then outline
      criteria to determine whether screening is appropriate for a given condition. A
      search for relevant articles is described followed by an outline of the steps
      used to appraise a screening study critically. An applicable study is examined in
      detail for such things as the quality of randomisation and outcomes measured. The
      results of this study are then applied to a patient considered for screening.

PMID- 8871459
TI  - Four years of problem-based learning: a student's perspective.
AB  - After four years as a student in a medical school using problem-based learning I
      still find it an excellent way to learn. Group work has developed my personal
      skills and abilities. Learning how to obtain knowledge on my own has given me
      independence and confidence. Motivation to study has been encouraged by early
      clinical experience. Training in critical thinking has been further enhanced by
      in-depth studies. Medical education at the University of Linkoping has developed
      over the years and a contributing factor has been students' involvement in
      designing the medical training. There are benefits and disadvantages with problem
      based learning, but on the whole it is an enjoyable and fruitful experience.

PMID- 8871457
TI  - Counselling for an HIV test.
AB  - Doctors may feel uncomfortable with the prospect of discussing a human
      immunodeficiency virus (HIV) antibody test with their patient. This is in part
      because they do not enquire about high risk activity as part of a medical
      history. With increasing medical and public awareness of both the clinical
      manifestations and social implications of HIV infection, it is important that all
      doctors receive guidance on how to deal with these issues. Counselling is not the
      usual term used to describe obtaining informed consent. In the general medical
      setting, tests for hepatitis B and syphilis are routinely carried out without
      specific consent even though results of these tests may have profound effects on
      both the patient and their sexual partners. However society and ethical
      considerations have made HIV testing different. HIV testing will inevitably
      become more widespread, and thus become a more routine part of patient
      investigation and management.

PMID- 8871458
TI  - Guidelines for the management of thrombophilia. Department of Haematology, The
      Royal London Hospital, Whitechapel, London, UK.
AB  - Although there are numerous risk factors for venous thromboembolic disease, the
      term 'thrombophilia' refers only to those familial or acquired disorders of the
      haemostatic system that result in an increased risk of thrombosis. The inherited
      thrombophilias include antithrombin III deficiency, resistance to activated
      protein C (factor V Leiden), protein C and protein S deficiencies as well as some
      rare forms of dysfibrinogenaemia. It is possible that other inherited conditions
      might also predispose to thrombosis. In contrast, when using the above
      definition, the antiphospholipid syndrome is the only genuine acquired
      thrombophilic state. Patients who have thromboembolic disease at a young age with
      no provoking event or who have a positive family history or whose thrombosis
      involves an unusual site should be investigated for thrombophilia. The management
      of a patient identified as having a laboratory abnormality associated with
      thrombophilia will depend on a variety of factors such as the patient's
      individual and family thrombotic history, the site of the thrombosis and the
      presence of other prothrombotic risk factors. The use of prophylactic
      anticoagulation during pregnancy and the puerperium requires particularly careful
      consideration in thrombophilic women. As more becomes known about the
      thrombophilias it will become possible to formulate more exact guidelines as to
      the management of these conditions.

PMID- 8871460
TI  - Coronary flow reserve and oesophageal dysfunction in syndrome X.
AB  - The relative prevalence of abnormalities of coronary flow reserve and oesophageal
      function was ascertained in 32 syndrome X patients with typical angina chest
      pain, a positive exercise test, and normal coronary arteries. Coronary flow
      reserve in response to a hyperaemic dose of papaverine was measured using an
      intracoronary Doppler catheter positioned in the left anterior descending
      coronary artery. An abnormal coronary flow reserve was defined as being < 3.0.
      Patients were investigated for oesophageal dysfunction by manometry and 24-hour
      pH monitoring. Thirteen patients had an impaired coronary flow reserve (group 1)
      and 19 patients had a normal flow reserve (group 2). Eight of the 13 group 1
      patients (62%) and 13 of the 19 group 2 patients (68%, p = NS) had evidence of
      oesophageal dysfunction on either manometry or pH studies. Therefore, a total of
      26 (81%) syndrome X patients had either an abnormality of coronary flow reserve
      or oesophageal dysfunction suggesting that chest pain in these patients may be
      due to myocardial ischaemia or oesophageal dysfunction, thus confirming the
      heterogeneous nature of this syndrome. The prevalence of oesophageal
      abnormalities was independent of any abnormalities of coronary flow reserve.

PMID- 8871461
TI  - Local anaesthesia for major general surgical procedures. A review of 116 cases
      over 12 years.
AB  - Between 1980 and 1992, 116 patients had either a simple mastectomy (32) or intra
      abdominal procedures (84) under local anaesthesia (0.5-1% lignocaine with 1:200
      000 adrenaline). A wide variety of general surgical procedures were feasible
      using only supplementary intravenous sedation (54%). Complications were uncommon
      and related to surgical procedure (three incorrect diagnoses, three procedures
      impossible) rather than the anaesthetic technique. There were no anaesthetic
      toxicity or postoperative problems. Local anaesthesia is extremely safe and
      facilitates larger surgical procedures than is generally appreciated.

PMID- 8871462
TI  - The risk of severe salicylate poisoning following the ingestion of topical
      medicaments or aspirin.
AB  - Apart from isolated reports of severe salicylate poisoning after ingesting an
      unusually large amount of a medicinal oil, there are no published data on the
      threat arising from attempted suicide with topical medicaments containing methyl
      salicylate or wintergreen oil compared with aspirin tablets. In this
      retrospective study, the admission plasma salicylate concentrations and clinical
      presentations were compared in 80 subjects who had taken aspirin tablets (n = 42)
      or topical medicaments (n = 38). The proportions of subjects being symptomatic
      were similar in the two groups. Although the admission plasma salicylate
      concentrations were generally higher in subjects who had ingested aspirin
      tablets, the two highest readings (4.3 and 3.5 mmol/1) belonged to two of the
      subjects who had taken topical medicaments. Because of its liquid, concentrated
      form and lipid solubility, methyl salicylate poses the threat of severe, rapid
      onset salicylate poisoning. The toxic potential of topical medicaments containing
      methyl salicylate or wintergreen oil should be fully appreciated by both
      physicians and the general public.

PMID- 8871463
TI  - Bleeding in a patient taking Lorenzo's oil: evidence for a vascular defect.
AB  - We describe a man with adrenoleukodystrophy receiving Lorenzo's oil (glycerol
      trioleate and glycerol trierucate) who developed purpura, petechiae, and
      bleeding. Bleeding time was markedly increased (>20 min), although he had only
      borderline thrombocytopenia (120 x 10(9)/1) and conventional platelet aggregation
      studies were normal (except for a borderline response to low concentration
      collagen), as were results using a new technique employing immobilised von
      Willebrand factor. Together these results suggest that bleeding in this man
      resulted from a defect in vascular wall function or in the interaction of
      platelets with the endothelium.

PMID- 8871464
TI  - Pancreaticopleural fistula: a rare complication of chronic pancreatitis.
AB  - Pancreaticopleural fistula is an uncommon sequelae of pancreatitis. The condition
      is often elusive, as respiratory rather than abdominal symptoms usually
      predominate and the fistula can be difficult to demonstrate radiologically.
      Confirmation is by demonstrating a high amylase content in the pleural aspirate
      relative to the serum. About half the fistulae will close with conservative
      treatment but persistent or recurrent effusions, often associated with stenosis
      or disruption of the main pancreatic duct, are an indication for surgery. The
      long-term outcome is good in 80-95% of cases. We report five patients with
      pleural effusion of pancreatic origin due to pancreaticopleural fistula.

PMID- 8871465
TI  - Pneumonitis complicating selective intra-arterial chemotherapy for locally
      advanced breast carcinoma.
AB  - We describe a case of pneumonitis in a patient receiving selective intra-arterial
      chemotherapy for locally advanced breast cancer.

PMID- 8871467
TI  - Concealed post-infarction left ventricular rupture--a diagnostic dilemma.
AB  - We describe a patient with post-infarction left ventricular rupture exhibiting
      several atypical features. A successful outcome was achieved after serendipitous
      surgery.

PMID- 8871466
TI  - Cerebral vasculitis following allopurinol treatment.
AB  - A 45-year-old man developed cerebral vasculitis associated with a systemic
      hypersensitivity response shortly after commencing treatment with allopurinol.
      The illness settled on withdrawal of the drug and no other cause was found.

PMID- 8871468
TI  - Abdominal pain in a young girl.
AB  - A 14-year-old girl was admitted to our hospital with peri-umbilical pain
      associated with obstipation and vomiting. Plain erect X-rays of the abdomen
      revealed multiple air fluid levels. A supine X-ray is shown in this figure.

PMID- 8871469
TI  - Cardioversion of atrial fibrillation.

PMID- 8871470
TI  - Use of face masks during a plague epidemic.

PMID- 8871471
TI  - Finasteride-related cutaneous vaculitis.

PMID- 8871472
TI  - A microscale model of bacterial swimming, chemotaxis and substrate transport.
AB  - In this paper, we introduce a mathematical and computational model at the
      microscale level of bacterial motility and chemotaxis coupled with the advection
      and diffusion of a biologically reacting substrate. The hydrodynamic interaction
      of a small bacterial population is explicitly modelled through the use of
      discrete representations of individual microbes. We use the immersed boundary
      method to couple microbial motion and the advection-diffusion of substrate with
      the full incompressible Navier-Stokes equations. Simulations using a preliminary
      two-dimensional model are presented, demonstrating the mutual dependence through
      the fluid media of several swimming bacteria. A run and tumble mechanism is
      introduced for simulating the chemotaxis of swimming bacteria.

PMID- 8871473
TI  - Desensitization and neurohumor modulation: a model of drug dependence II.
AB  - A theoretical model of drug tolerance and dependence is presented, based on the
      assumption that, besides their own function, some neurohumors may also modulate
      the output of other neurohumors. If the receptors of both neurohumors are rapidly
      desensitized and resensitized by their natural ligands, but slowly by drugs,
      prolonged exposure to drugs will necessarily lead to drug tolerance and
      dependence. This model proposes a function for co-transmitters and, applied to
      opioid and catecholamine neurohumors and drugs, it explains the presence of
      enkephalin in sympathetic neurons, the release of catecholamine neurohumors by
      opiates, the fact that signs of opiate abstinence are largely autonomic symptoms,
      the attenuation of the opiate abstinence syndrome by alpha2 agonists and its
      exacerbation by alpha2 antagonists, the analgesic action of excitement, and the
      increased toxicity of morphine in animals treated with 6-hydroxydopamine. The
      model also suggests possible interpretations for the late effects of large opiate
      doses, hyperalgesia caused by very small opiate doses, certain symptoms of
      autism, and sudden infant death syndrome.

PMID- 8871474
TI  - Neural network prediction of the HIV-1 protease cleavage sites.
AB  - A back propagation neural network method has been developed to study the pattern
      of polypeptides that can be cleaved by the HIV-1 protease. This method can
      incorporate many characteristics of the peptides, such as hydrophobicity, beta
      sheet and alpha-helix propensities. Mutations can also be applied to probe the
      most important factors that influence the cleavage.

PMID- 8871475
TI  - A molecular model of braid-like DNA structure.
AB  - The three-dimensional molecular models of DNA triple helices and triple-stranded
      brain-like structure were built up by molecular architecture, and their
      structural features and energy decomposition were examined. The results showed:
      (i) The base triplet is the element forming braid-like and triple helix DNA; (ii)
      Under specified conditions, DNA could form the triplet-stranded braid-like
      structure; (iii) DNA stability of the braid-like structure is less than that of
      the triple helix structure.

PMID- 8871476
TI  - A patient who keeps giving expensive gifts.

PMID- 8871477
TI  - Football injuries: tackling the damage.

PMID- 8871478
TI  - Intervention in coronary artery disease.

PMID- 8871479
TI  - How to handle the new-look MCQ.

PMID- 8871480
TI  - Diabetes in the young.

PMID- 8871481
TI  - Managing stridor in children.

PMID- 8871482
TI  - 'My child won't sleep'.

PMID- 8871483
TI  - Rationale for the use of vitamin D3 analogues in psoriasis.

PMID- 8871484
TI  - Pharmacology, pharmacokinetics and metabolism.

PMID- 8871485
TI  - Efficacy of calcipotriol in psoriasis.

PMID- 8871487
TI  - Calcipotriol in other dermatological disorders.

PMID- 8871486
TI  - Safety and tolerability of calcipotriol in psoriasis.

PMID- 8871488
TI  - Too few "bad doctors" in Delaware?

PMID- 8871489
TI  - Case report: plasma cell granuloma of the lung.

PMID- 8871490
TI  - A medical ethics report.

PMID- 8871491
TI  - Glimpses of 20th century medicine and a preview of the 21st century.

PMID- 8871492
TI  - Medicare HMOs: part of the solution or part of the problem in the struggle for
      cost containment?
AB  - The correct answer for salvage of the Medicare program while maintaining
      acceptable medical care is clearly not available today. Managed care programs for
      seniors have been an option in the last decade and plans are expanding rapidly
      into previously untapped areas. Some programs can indeed provide a multiplicity
      of services and thereby truly integrate and improve existing care plans. Others
      have less clear cut advantages. For any senior contemplating the options
      available for medical care under Medicare, HMOs and Medigap type instruments, the
      most salient advice is "buyer beware." A complete understanding of the options
      gained and lost by changing medical insurance coverage is essential.

PMID- 8871493
TI  - Primary care in the emergency room.

PMID- 8871494
TI  - Bacterial infections and deep implants.

PMID- 8871495
TI  - Low back pain.

PMID- 8871497
TI  - Allergy testing.

PMID- 8871496
TI  - Joint ventures.

PMID- 8871498
TI  - The rights of every man and woman in the United States.

PMID- 8871499
TI  - Interview with George R. Laufenberg. Interview by Bill Berlin.

PMID- 8871500
TI  - Financing care for the uninsured: the dilemma vexes New Jersey hospitals and
      payers.
AB  - New Jersey's diverse constituencies and special interest groups don't usually
      agree on a public policy issue. However, almost everyone in the public policy
      arena agrees that hospitals should treat people who show up in emergency
      departments with problems requiring medical attention. For over a decade, Garden
      State policymakers, payers, and providers have faced the dilemma of excess demand
      on hospitals that treat the uninsured. This demand has risen due to increasing
      health care costs, development of costly technology, state deregulation of
      hospital payments, and employers' reluctance to insure workers and their families
      coupled with a mobile workforce holding part-time and seasonal jobs. The fiscal
      solvency of inner-city hospitals is threatened yet the problem continues to elude
      resolution.

PMID- 8871501
TI  - Model of comprehensive diagnosis and care for breast cancer patients.

PMID- 8871502
TI  - Metastases from metastatis: a careful examination.

PMID- 8871503
TI  - Drug testing of student athletes: a policy concern.

PMID- 8871504
TI  - The emotional impact of MS diagnosis.

PMID- 8871505
TI  - New Jersey health care enters the electronic age.
AB  - A Trenton internist confers with a Newark neurologist without picking up the
      telephone. An emergency room physician learns that an unconscious accident victim
      has diabetes and heart problems. A local doctor administers antibiotics in a
      school, hours after a case of meningitis is diagnosed. A legislator knows a new
      law governing health care standards is working weeks after it was enacted.

PMID- 8871506
TI  - Prostate cancer: essays on decision making.

PMID- 8871507
TI  - The future of a state medical journal.

PMID- 8871508
TI  - Radiation oncology at the centennial.
AB  - 1995 marks the centennial year of the discovery of x-rays. The medical profession
      advanced rapidly following Roentgen's discovery of the x-ray. Every aspect of
      medicine came to rely on radiology in some way. The x-ray not only revolutionized
      diagnostic medicine, it transformed therapeutic medicine as well. Only months
      after its discovery, the x-ray was being used with therapeutic intent, thus began
      radiation therapy. We can examine the development of radiation oncology in
      several periods.

PMID- 8871509
TI  - Medical information on the Internet.
AB  - Connecting to the Internet allows health care professionals to access medical
      information at computer sites worldwide, to search databases, communicate with
      peers, obtain continuing education, retrieve images and software, obtain drug
      information and access statistical data. Users can access sites with "virtual
      patients," search library catalogs, locate jobs and post resumes, and explore
      conference sites and topics. Rural health care professionals can have access to
      medical information equivalent to their urban peers. Information is usually
      available over the Internet much more rapidly than through traditional print
      methods.

PMID- 8871510
TI  - Should drugs be decriminalized?

PMID- 8871511
TI  - J. Marion Sims and Nathan Bozeman: the fight for priority in the surgical repair
      of vesico-vaginal fistula.

PMID- 8871512
TI  - H. pylori eradication therapy.

PMID- 8871513
TI  - Doctor, why won't the pain go away?

PMID- 8871515
TI  - If you're dead, press 9.

PMID- 8871514
TI  - Spoil your patients--they love it.

PMID- 8871516
TI  - A new Federation.

PMID- 8871517
TI  - Iowa physicians, PAs see evolving relationship.
AB  - No matter what side of the professional fence you're on, it's obvious that
      physicians' relationships with allied health practitioners are changing. This
      article examines the general condition of the physician/PA relationship in Iowa.

PMID- 8871518
TI  - Who shoulders the risk? Liability and allied health providers.

PMID- 8871519
TI  - Changing trends in varicose vein treatment.

PMID- 8871520
TI  - Continuing education through the world wide web.

PMID- 8871521
TI  - Different rifampicin inactivation mechanisms in Nocardia and related taxa.
AB  - Mycolic acid-containing bacteria inactivate rifampicin in a variety of ways such
      as glucosylation, ribosylation, phosphorylation and decolorization. These
      inactivations were found to be a species-specific phenomena in Nocardia and
      related taxa. Gordona, Tsukamurella and fast-growing Mycobacterium modified
      rifampicin by ribosylation of the 23-OH group of the antibiotic. Such
      ribosylation was not observed in Rhodococcus and Corynebacterium, but
      phosphorylation of the 21-OH group of rifampicin was observed in one strain of
      Rhodococcus. Nocardia modified the antibiotic by glucosylation (23-OH group) and
      phosphorylation, but ribosylation was not observed.

PMID- 8871522
TI  - Simple method for detection of Clostridium botulinum type A to F neurotoxin genes
      by ploymerase chain reaction.
AB  - A polymerase chain reaction (PCR)-based method was established to detect each
      type of neurotoxin genes of Clostridium botulinum types A to F by employing the
      oligonucleotide primer sets corresponding to special regions of the light chains
      of the neurotoxins. In this procedure, the PCR products were easily confirmed by
      restriction enzyme digestion profiles, and as little as 2.5 pg of template DNAs
      from toxigenic strains could be detected. The specific PCR products were obtained
      from toxigenic C. botulinum types A to F, a type E toxin-producing C. butyricum
      strain, and a type F toxin-producing C. baratii strain, but no PCR product was
      detected in nontoxigenic strains of C. botulinum and other clostridial species.
      The neurotoxin genes were also detected in food products of a seasoned dry salmon
      and a fermented fish (Izushi) which had caused type E outbreaks of botulism.
      Therefore, it is concluded that this PCR-based detection method can be used for
      the rapid diagnosis of botulism.

PMID- 8871523
TI  - Borrelia burgdorferi sensu lato in an endemic environment: wild sika deer (Cervus
      nippon yesoensis) with infected ticks and antibodies.
AB  - Ticks and blood samples were collected from wild sika deer (Cervus nippon
      yesoensis) during a hunting season (August to October) of 1991 at a selected
      location in Hokkaido, Japan. Ixodes persulcatus (adult and nymph) and I. ovatus
      (adult) were the common ticks on sika deer. Spirochetes were detected in the
      midgut of the ticks by the indirect peroxidase-conjugated antibody staining
      method and by dark-field microscopy after cultivation. By the reactive pattern of
      monoclonal antibodies, isolates were considered to belong to Borrelia garinii or
      B. japonica. In an antibody test, the percentage of seropositive deer was 69.0%.
      Most of the adult sika deer were positive for antibodies to the spirochetes.
      There are significant age-dependency in antibody level and seropositive rate. The
      surveillance of deer should be valuable in monitoring the transmission risk of B.
      burgdorferi sensu lato in nature.

PMID- 8871524
TI  - Polymerase chain reaction for the detection of Chlamydia psittaci in the feces of
      budgerigars.
AB  - The polymerase chain reaction (PCR) targeting the ompA gene of Chlamydia psittaci
      was evaluated for its ability to detect chlamydiae in fecal specimens of
      budgerigars as compared with isolation procedures using cell culture and
      embryonated egg inoculations. Several procedures for PCR template DNA preparation
      were compared so as to determine their detection levels for chlamydiae propagated
      in cell culture in the presence of fecal materials. Tween-20 and proteinase K
      treatments followed by centrifugation of the template DNA were found to be an
      appropriate procedure for DNA preparation for primary PCR. Subsequent nested PCR
      was shown to detect 4.8 IFU/ml or 84 particles/ml of chlamydiae. Chlamydiae in 50
      fecal specimens from apparently healthy budgerigars were examined by nested PCR
      and several other methods. Nested PCR detected chlamydiae at a higher rate
      (12/50, 24%) than the isolation procedure in embryonated eggs (6/50, 12%).
      Primary PCR combined with the isolation procedure in cell culture gave a
      detection rate (5/50, 10%) similar to that of isolation from embryonated eggs.
      Detection rates by primary PCR (1/50, 2%) and in cell culture (0%) were inferior
      to the other procedures.

PMID- 8871525
TI  - A new primer pair for detection of Chlamydia pneumoniae by polymerase chain
      reaction.
AB  - In order to improve the detection and identification of Chlamydia pneumoniae, new
      primers for polymerase chain reaction (PCR) were designed based on the DNA base
      sequence within the 53-kDa protein gene, which is specific for C. pneumoniae. The
      primers permitted the identification of 24 C. pneumoniae strains collected from
      different geographical locations, but no reaction was observed with C.
      trachomatis, C. psittaci nor C. pecorum. The primers were unable to amplify the
      DNA of bacteria commonly related to respiratory tract infections. The positive
      amplification was achieved with only 9 EBs/assay. Therefore, the new primers seem
      to be useful in the diagnosis of C. pneumoniae infections.

PMID- 8871526
TI  - Crystallization of synthetic Escherichia coli-type lipid A.
AB  - Synthetic Escherichia coli-type lipid A formed hexagonal plate crystals when it
      was precipitated by the addition of 2 volumes of 95% ethanol containing 375 mM
      MgCl2 and incubated in 70% ethanol containing 250 mM MgCl2 at 4 C for 10 days.
      Analyses of crystals by electron diffraction and synchrotron X-ray diffraction
      showed that crystals consist of hexagonal lattices with the lattice constant (a
      side of the lozenge as a unit cell on the basal plane) of 4.62 angstrom and the
      longitudinal axis (perpendicular to the basal plane) of 49.3 +/- 1.3 angstrom.
      Results suggest that the previous finding that various kinds of R-form
      lipopolysaccharides crystallized but free lipid A isolated by acid hydrolysis
      from Re lipopolysaccharide did not crystallize under the same experimental
      conditions (Kato et al, J. Bacteriol., 172:1516-1528, 1990) is due to structural
      changes of lipid A occurring during the procedure of isolation of free lipid A.

PMID- 8871527
TI  - Enhanced engraftment of HTLV-I-infected human T cells in severe combined
      immunodeficiency mice by anti-asialo GM-1 antibody treatment.
AB  - The effects of anti-asialo GM-1 antibody (AAGM) treatment on the engraftment of
      human T-cell leukemia virus type I (HTLV-I)-infected human T cells in severe
      combined immunodeficiency (SCID) mice were studied. The frequency of tumor
      formation in an HTLV-I-transformed human T-cell line, MT-2 cells, at the site of
      inoculation was significantly higher in AAGM-treated than untreated mice
      (P<0.05): 16/18 (89%) and 16/26 (62%), respectively. The promotive effect of AAGM
      treatment on tumor development was marked in the early stage (less than 3 weeks),
      suggesting that the immediate reaction of natural killers to the inoculated cells
      may be important for the prevention of tumor development. The surface phenotypes
      and clonality of the tumor cells were the same as the MT-2 cells inoculated.
      Inoculation of peripheral blood mononuclear cells (PBMC) from one of the 4 adult
      T-cell leukemia/lymphoma (ATL) patients resulted in the development of tumors in
      AAGM-treated SCID mice. However, the surface phenotypes of the cells from these
      tumors were a mixture of B cells and T cells, suggesting that these tumors
      consisted of Epstein-Barr virus-transformed B cells and HTLV-I-transformed T
      cells. In addition, HTLV-I was detected by polymerase chain reaction in various
      organs of the mice inoculated with PBMC from the ATL patient and the asymptomatic
      carrier examined. These results suggest that elimination of natural killer
      function by AAGM treatment is important, although such treatment is not always
      necessary for the engraftment of HTLV-I-infected cells in SCID mice.

PMID- 8871528
TI  - Activation of unusual Mac-1+CD4-CD8- T cells bearing (alpha)(beta) antigen
      receptor in murine lungs during infection with Mycobacterium bovis BCG:
      regulation by interferon-gamma.
AB  - We have recently (Kawakami et al, Immunol. Lett. 1995;46: 143) demonstrated that
      unusual Mac-1+CD4-CD8- T cells bearing (alpha)(beta) antigen receptor (Mac-1+
      (alpha)(beta) T cells) reside in a considerable proportion in murine lungs. The
      present study was performed to examine the dynamics of accumulation of these
      cells in the lungs following intravenous administration of Mycobacterium bovis
      BCG (BCG). Mac-1+ (alpha)(beta) T cells accumulated rapidly 24 hr after
      infection, followed by a gradual increase over the observation period of 15 days.
      Furthermore, the expression of Ia, ICAM-1 and FcgammaR II/III on their surface
      intensified dramatically after BCG infection. The kinetics of enhancement of Ia
      expression was slower than that of ICAM-1, with the maximum level attained in one
      day in the latter molecule but in two weeks in the former. Neutralization of
      endogenous IFN-gamma by specific mAb completely blocked the augmented expression
      of Ia on Mac-1+ (alpha)(beta) T cells after BCG infection, but did not have any
      significant effect on that of ICAM-1. In contrast, in vivo administration of IFN
      gamma enhanced the expression of ICAM-1 as well as that of Ia. Our results
      indicate that accumulation of Mac-1+ (alpha)(beta) T cells within the lung is
      associated with a differential change in the expression of surface antigens, and
      suggest that these cells may play a role in the host defense against
      mycobacterial infection.

PMID- 8871529
TI  - Tumor-specific transplantation resistance in mice after treatment of initial
      tumors with Streptococcus thermophilus.
AB  - Antitumor activity observed by treatment with Streptococcus thermophilus was
      further investigated. The mice cured from fibrosarcoma by treatment with heat
      killed preparation of S. thermophilus, when challenged with fibrosarcoma failed
      to take up the tumor. However, these cured mice when challenged with sarcoma-180
      or Ehrlich ascites carcinoma, did not show significant changes in tumor take
      and/or survival compared to their respective controls. Similarly, mice cured from
      sarcoma-180 were challenged with fibrosarcoma, sarcoma-180 or Ehrlich ascites
      carcinoma. Though there was no change in the mean survival time (MST) of the
      dying mice regarding sarcoma-180 or Ehrlich ascites carcinoma, there was 50 and
      30% increase in the number of mice that showed total regression respectively over
      controls. However, there was no difference in the growth rate of fibrosarcoma.
      Similar observations were made with mice cured from Ehrlich ascites carcinoma,
      challenged with these tumors. These findings thus suggest that the antitumor
      response was tumor-specific and that tumor-associated antigens may have a role in
      imparting this specificity. Bacterial treatment non-specifically augmented this
      primary response.

PMID- 8871530
TI  - The thermostable direct hemolysin gene (tdh) of Vibrio hollisae is dissimilar in
      prevalence to and phylogenetically distant from the tdh genes of other vibrios:
      implications in the horizontal transfer of the tdh gene.
AB  - Vibrio hollisae strains isolated recently from patients in various locations were
      examined for the presence of the thermostable direct hemolysin gene (tdh) using
      nucleic acid hybridization and polymerase chain reaction assays. The results were
      consistent with the previous finding that all strains of V. hollisae carry the
      tdh gene. In contrast, the tdh gene has been detected in a minority of strains
      for other Vibrio species (V. parahaemolyticus, V. cholerae non-O1, and V.
      mimicus). Detailed phylogenetic analysis showed that the tdh genes of the non-V.
      hollisae species were very closely related to each other and that the tdh gene of
      V. hollisae was distantly related to the tdh genes of the non-V. hollisae
      species. These results and the proposed insertion sequence-mediated tdh transfer
      mechanism suggest that the tdh gene may have been maintained stably in V.
      hollisae and that the tdh genes of the non-V. hollisae species may have been
      involved in recent horizontal transfer.

PMID- 8871531
TI  - Reservoir competence of the vole, Clethrionomys rufocanus bedfordiae, for
      Borrelia garinii or Borrelia afzelii.
AB  - In autumn of 1994 and spring of 1995, we examined Borrelia infection among
      Microtinae voles, Clethrionomys rufocanus bedfordiae, in Hokkaido, Japan. In BSK
      culturing of the earlobe tissues of 45 C. rufocanus bedfordiae captured, twelve
      rodents were positive for Borrelia. Eight isolates were used for the polymerase
      chain reaction (PCR) and the restriction fragment length polymorphism (RFLP)
      analysis. According to the results, these isolates were classified into B.
      garinii or B. afzelii. It is considered that a common vole, C. rufocanus
      bedfordiae, plays a significant role in the transmission and maintenance of B.
      garinii and B. afzelii, similar to the role of Apodemus speciosus mice.

PMID- 8871532
TI  - Characterization by Western blotting of mouse intestinal glycoproteins bound by
      Escherichia coli heat-labile enterotoxin type I.
AB  - Escherichia coli heat-labile enterotoxin type I (LT-I)-binding galactoproteins,
      which were not recognized by cholera toxin, were detected in intestinal
      epithelial cells of BALB/c mouse by Western blotting. Inhibitory studies using
      lectins and modifications of sugar chain suggest that LT-I recognizes certain
      mucin-type sugar chains containing the terminal Galbeta1-3GalNAc sugar sequence
      in the galactoproteins. The terminal sugar sequence is identical to that of GM1
      ganglioside, the well-documented functional receptor for LT-I.

PMID- 8871533
TI  - Analysis of of the epitopes recognized by mouse monoclonal antibodies directed to
      Yersinia enterocolitica heat-shock protein 60.
AB  - To determine amino acid sequences of the epitopes recognized by monoclonal
      antibodies (mAbs) 3C8 and 5C3 directed against Yersinia enterocolitica heat-shock
      protein (HSP60), a dot blot analysis was performed using synthesized peptides of
      Y. enterocolitica HSP60 such as peptides p316-342, p327-359, p340-366, p316-326,
      p316-321, p319-323, and p321-326 which represent positions of amino acids in Y.
      enterocolitica HSP60. The dot blot analysis revealed that 5C3 mAb reacted with
      p316-342, p316-326 and p321-326, and 3C8 mAb p316-342 and p316-326. These results
      indicate that the epitopes recognized by the mAbs were associated with eleven
      amino acids, Asp Leu Gly Gln Ala Lys Arg Val Val Ile Asn, of p316-326. The
      sequence homology between p316-326 of Y. enterocolitica HSP60 and the rest of the
      HSP60 family suggests that the five amino acids of Lys, Arg, Val, Ile and Asn,
      which are highly conserved in the HSP60 family, might be related with the epitope
      recognized by 3C8. In contrast, it was also demonstrated that three amino acids
      of Leu, Gly and Val, which are not well conserved in the HSP60 family, might be
      related to the epitope recognized by 5C3.

PMID- 8871534
TI  - Different sensitivity to streptolysin-O of cells in macrophage lineage.
AB  - We have surveyed the sensitivity of cells in macrophage lineage to Streptolysin-O
      (SLO). SLO had cytotoxic activity on immature myeloid cell lines such as M1 and
      WEHI-3BD+. SLO was toxic to the cells after a 2-hr incubation. However, mature
      macrophage cell lines such as A640-BB-2, J774, and P388D1 were not sensitive to
      the same dose of SLO. After M1 cells were treated with leukemia inhibitory factor
      (LIF), a differentiation-inducer to macrophage, these cells became insensitive to
      SLO in one day. This cytotoxic action of SLO was inhibited by pretreatment with
      anti-Streptolysin-O antibody or cholesterol. These results indicate that SLO has
      different effects on macrophage lineage.

PMID- 8871535
TI  - Proliferation and teratogenicity of Aino virus in chick embryos.
AB  - Aino virus (AIV; JaNAr 28 strain) 10(3) TCID50/0.2 ml was inoculated in the yolk
      sac of 8-day-old chick embryos. Recovery and titration of the virus from various
      organs including the central nervous system (CNS) and skeletal muscle were
      performed at 2, 4, 7, 10 and 13 days after inoculation (PI). AIV was
      systematically disseminated and proliferated even 2 days PI. The titers of the
      recovered virus from the CNS and from skeletal muscle was the highest at 4 days
      PI and declined with time, whereas hydranencephaly, arthrogryposis and cerebellar
      hypoplasia developed at 7 days PI and gradually progressed until 13 days PI.

PMID- 8871536
TI  - Glioma invasion in vitro: regulation by matrix metalloprotease-2 and protein
      kinase C.
AB  - A hallmark of invasive tumors is their ability to effect degradation of the
      surrounding extracellular matrix (ECM) by the local production of proteolytic
      enzymes, such as the matrix metalloproteases (MMPs). In this paper, we
      demonstrate that the invasion of human gliomas is mediated by a 72 kDa MMP,
      referred to as MMP-2, and provide further evidence that the activity of MMP-2 is
      regulated by protein kinase C (PKC). The invasiveness of five human glioma cell
      lines (A172, U87, U118, U251, U563) was assessed in an in vitro invasion assay
      and was found to correlate with the level of MMP-2 activity (r2 = 0.95); in
      contrast, the activity of this 72 kDa metalloprotease was barely detectable in
      non-invasive control glial cells (non-transformed human astrocytes and
      oligodendrocytes). Treatment with 1,10-phenanthroline, a metalloprotease
      inhibitor, or with a synthetic dipeptide, containing a blocking sequence (ala
      phe) specific for MMPs, resulted in a > 90% reduction in glioma invasion.
      Furthermore, this MMP-2 activity could be inhibited by the treatment of tumor
      cells with calphostin C, a specific inhibitor of PKC. Glioma cell lines treated
      with calphostin C demonstrated a dose-dependent decrease (IC50 = 30 nM) in tumor
      invasiveness with a concomitant reduction in the activity of the MMP-2.
      Conversely, treatment of non-invasive control astrocytes with a PKC activator
      (phorbol ester) led to a corresponding increase in their invasiveness and
      metalloprotease activity. These findings support the postulate that MMP-2
      activity constitutes an important effector of human glioma invasion and that the
      regulation of this proteolytic activity can be modulated by PKC.

PMID- 8871537
TI  - CD44 exon 6 expression as a possible early prognostic factor in primary node
      negative breast carcinoma.
AB  - Breast cancer is the most common female malignancy affecting approximately one
      woman in eight. Many attempts have been made to define markers which may have
      potential clinical applications in diagnosis as well as therapy. New isoforms of
      CD44 with alternative spliced exons have recently been described. We studied the
      expression of CD44 exon 6 using a semi-quantitative RT-PCR reaction on a panel of
      25 normal breast specimens, 10 mammary fibroadenomas, eight cystic samples and 52
      primary breast tumors. Significant correlation was found between CD44 exon 6
      expression and the overall survival of the N-M-population, P = 0.032, (logrank
      test by Mantel's method). The same result was also observed for the disease-free
      survival, P = 0.000002 (logrank test by Mantel's method). CD44 exon 6 expression,
      as detected by our RT-PCR-based method, might be a useful prognostic indicator of
      metastasis in breast cancer. However, these preliminary results need to be
      confirmed by later retrospective and prospective studies on a larger number of
      patients.

PMID- 8871538
TI  - Quantitative and qualitative differences in growth, invasion and lung
      colonization of an anaplastic and a papillary human thyroid cancer cell line in
      vitro and in vivo.
AB  - Invasion and metastasis remain major reasons for failure of anti-cancer therapy.
      Cell lines derived from human carcinomas are frequently used to investigate the
      molecular mechanisms that underlie invasion and metastasis. Unfortunately many of
      these cell lines do not retain the malignant characteristics of their parental
      tumors. We therefore conducted a series of experiments in vivo and in vitro to
      identify which aspects of malignancy of a papillary (NPA'87) and an anaplastic
      (DR090-1) thyroid carcinoma were consistent with the pathology of the parental
      tumor types. We evaluated tumor growth, invasion and metastasis of DRO90-1 and
      NPA'87 in vivo following inoculation of the tumor cells under the dermis, under
      the renal capsule and into the lateral tail vein of nude mice. This evaluation in
      vivo showed that the anaplastic carcinoma had a faster growth rate compared with
      the papillary carcinoma. Furthermore, the papillary carcinoma cells could destroy
      and infiltrate surrounding tissue but were not capable of extravasation and
      colonization of lung tissue. The anaplastic cells formed lung nodules following
      injection into the tail vein of nude mice. This lung colonizing capability of
      DRO90-1 correlated with their capacity to secrete an active 62 kDa gelatinase and
      to migrate through reconstituted basement membrane in vitro.

PMID- 8871539
TI  - A rapid and sensitive fluorometric screening assay using YO-PRO-1 to quantify
      tumour cell invasion through Matrigel.
AB  - A new quantitative assay for the study of tumour cell invasion in vitro is
      described. Employing the novel fluorescent dye YO-PRO-1, cells that penetrate
      Matrigel-coated transwells are counted on the basis of dye-bound cellular nucleic
      acid content. Following transmigration, the cells in the lower compartments are
      lysed by freezing in water. After a brief incubation with YO-PRO-1, nucleic acid
      or DNA content is measured as fluorescence intensity in 96-well microplates and
      quantitated by a cell- or DNA-calibration curve. Using standard curves, a linear
      relationship between fluorescence intensity and cell number was found in the
      range tested (from 100 to 80 000 cells). The mean relative intra- and inter-assay
      variability of the cell quantitation in this range was 3.5 and 4.2%,
      respectively. When applied to Matrigel invasion studies, as few as 400 cells
      could be counted. The quantitation could be performed within 3 h. HCT 116, MDA MB
      231 and HT 29 cells were investigated as examples of tumour cells with different
      invasive abilities in the 48-h Matrigel invasion assay. Using YO-PRO-1, 6.5 +/-
      0.6% invasive HCT 116 cells and 52.6 +/- 4.5% MDA MB 231 cells (percentage of the
      inoculated cell population) were measured. HT 29 cells were practically non
      invasive. These results were confirmed by visual scoring of DAPI-stained nuclei.
      In conclusion, the main advantages of the assay are its sensitive, reproducible
      and rapid quantitation of tumour cell invasion in vitro and the applicability to
      extended sample numbers by measuring in 96-well microplates.

PMID- 8871540
TI  - Histopathologic analysis of bone marrow and bone metastasis in murine
      neuroblastoma.
AB  - To elucidate the development of bone metastasis in human neuroblastoma, bone
      marrow and bone metastases were analysed histologically in a hematogeneous
      metastasis model of murine neuroblastoma. The bone marrow metastasis occurred
      initially in the bone marrow sinusoid where tumor cells adhered and extravasated
      to bone marrow parenchyma, resulting in the formation of nodular lesions in the
      medullary cavity. The nodular lesions eventually progressed to diffuse lesions
      segmentally occupying the medullary cavity. During the establishment of the
      diffuse lesions, tumor cells invaded cancellous bone and/or bone cortex,
      resulting in bone metastasis. Such nodular or diffuse bone marrow metastatic
      lesions occurred sporadically in a variety of bones. To improve the results of
      treatment for neuroblastoma, the characteristics of the bone marrow and the bone
      metastases demonstrated in this study should be considered in the diagnosis and
      treatment of this disease.

PMID- 8871541
TI  - An in vitro invasion model for human renal cell carcinoma cell lines mimicking
      their metastatic abilities.
AB  - We developed a modified in vitro invasion assay system using monolayers of
      vascular endothelial cells. A type I collagen gel was formed in plastic dishes,
      and overlaid with type IV collagen. Calf pulmonary arterial endothelial (CPAE)
      cells were seeded onto these plates, and incubated until they reached confluence.
      Five human renal cell carcinoma cell lines with various metastatic potentials in
      vivo were then seeded on the monolayer CPAE cells, and their colony formation and
      invasion activities were examined for 9 days. At day 4, the highly metastatic
      cell lines increased the number of colony foci on monolayer CPAE cells several
      fold higher than their poorly metastatic counterpart. The horizontal spreading
      patterns were also different between poorly and highly metastatic cell lines. On
      day 9, the number of carcinoma foci that penetrated the monolayer of CPAE cells
      and type IV collagen sheets into type I collagen gels in highly metastatic cell
      lines greatly increased as compared with that of poorly metastatic cell lines.
      Our in vitro invasion assay using monolayer CPAE cells would be useful to
      evaluate protease activities and colony formation during invasion.

PMID- 8871542
TI  - SP1-binding elements, within the common metaxin-thrombospondin 3 intergenic
      region, participate in the regulation of the metaxin gene.
AB  - Metaxin (Mtx) is an essential nuclear gene which is expressed ubiquitously in
      mice and encodes a mitochondrial protein. The gene is located upstream and is
      transcribed divergently from the thrombospondin 3 (Thbs3) gene; 1352 nucleotides
      separate the putative translation start sites. Although the Mtx and Thbs3 genes
      share a common intergenic region, transient transfection experiments in rat
      chondro-sarcoma cells and in NIH-3T3 fibroblasts demonstrated that the elements
      required for expression of the Mtx gene are situated within a short proximal
      promoter and have no major effect on the transcription of Thbs3. The metaxin -
      377 bp promoter contains four clustered GC boxes between nucleotides --146 and -
      58 and an inverted GT box between nucleotides --152 and --161, but does not
      contain TATA or CCAAT boxes. Like many genes regulated by a TATA-less promoter,
      the transcription start site of metaxin is heterogeneous. The major start site is
      only 13 bp upstream from the putative translation start site. Electrophoretic
      mobility shift, competition and supershift assays showed that the ubiquitous
      transcription factor, Sp1, and, to a lesser extent, the Sp1-related protein, Sp3,
      bind to four of these Sp1-binding motifs. Co-transfection of metaxin promoter
      luciferase constructs and an Sp1 expression vector into Schneider Drosophila
      cells, which do not synthesize Sp1, demonstrated that the metaxin gene is
      activated by Sp1. Deletion of the four upstream Sp1-binding elements, on the
      other hand, demonstrated that these motifs are superfluous in context of the
      larger Mtx promoter. Thus, despite the potential for common regulatory
      mechanisms, the available evidence indicates that the Mtx minimal promoter does
      not significantly affect Thbs3 gene expression.

PMID- 8871543
TI  - The central pseudoknot in 16S ribosomal RNA is needed for ribosome stability but
      is not essential for 30S initiation complex formation.
AB  - To examine the function of the central pseudoknot in 16S rRNA, we have studied
      Escherichia coli 30S subunits with the A18 mutation in this structure element.
      Previously, this mutation, which changes the central base pair of helix 2, C18-
      G917, to an A18xG917 mismatch, was shown to inhibit translation in vivo and a
      defect in initiation was suggested. Here, we find that the mutant 30S particles
      are impaired in forming 70S tight couples and predominantly accumulate as free
      30S subunits. Formation of a 30S initiation complex, as measured by toeprinting,
      was almost as efficient for mutant 30S subunits, derived from the tight couple
      fraction, as for the wild-type control. However, the A18 mutation has a profound
      effect on the overall stability of the subunit. The mutant ribosomes were
      inactivated by affinity chromatography and high salt treatment, due to easy loss
      of ribosomal proteins. Accordingly, the particles could be reactivated by partial
      in vitro reconstitution with 30S ribosomal proteins. Mutant 30S subunits from the
      free subunit fraction were already inactive upon isolation, but could also be
      reactivated by reconstitution. Apparently, the inactivity in initiation of these
      mutant 30S subunits is, at least in part, also due to the lack of essential
      ribosomal proteins. We conclude that disruption of helix 2 of the central
      pseudoknot by itself does not affect the formation of a 30S initiation complex.
      We suggest that the in vivo translational defect of the mutant ribosomes is
      caused by their inability to form 70S initiation complexes.

PMID- 8871544
TI  - The amino-terminal domain of the transcription termination factor TTF-I causes
      protein oligomerization and inhibition of DNA binding.
AB  - The transcription termination factor TTF-I binds specifically to an 18 bp DNA
      element in the murine ribosomal gene spacer and mediates termination of RNA
      polymerase I transcription. In this study, we have compared DNA binding and
      termination activity of recombinant full-length TTF-I (TTF-Ip130) with two
      deletion mutants lacking 184 and 322 N-terminal amino acids, respectively. All
      three proteins exhibit similar termination activity, but the DNA binding of TTF
      Ip130 is at least one order of magnitude lower than that of the deletion mutants,
      indicating that the N-terminus represses the interaction of TTF-I with DNA. The
      inhibitory effect of the N-terminus can be transferred to a heterologous DNA
      binding domain and is separable from other activities of TTF-I. We show by
      several methods that TTF-Ip130, the N-terminal domain alone, and fusions of the N
      terminus with the DNA binding domain of Oct2.2 form stable oligomers in solution.
      Thus, in contrast to previous studies suggesting that activation of TTF-I occurs
      through proteolysis, we demonstrate that full-length TTF-I mediates termination
      of rDNA transcription in vivo and in vitro and that the oligomerization state of
      TTF-I may influence its DNA binding activity.

PMID- 8871545
TI  - Functional analysis of the DNA-stimulated ATPase domain of yeast SWI2/SNF2.
AB  - The yeast SWI2/SNF2 polypeptide is a subunit of the SWI/SNF protein complex that
      is required for many transcriptional activators to function in a chromatin
      context. SWI2 is believed to be the founding member of a new subfamily of DNA
      stimulated ATPases/DNA helicases that includes proteins that function in DNA
      repair (RAD5, RAD16, ERCC6), recombination (RAD54), transcription (MOT1, ISWI,
      brm, BRG1, hBRM) and cell cycle control (STH1). We have created a set of 16
      mutations within the SWI2 ATPase domain and have analyzed the functional
      consequences of these mutations in vivo. We have identified residues within each
      of the seven ATPase motifs that are required for SWI2 function. We have also
      identified crucial residues that are interspersed between the known ATPase
      motifs. In contrast, we identify other highly conserved residues that appear to
      be dispensable for SWI2 function. We also find that single amino acid changes in
      ATPase motifs IV and VI lead to a dominant negative phenotype. None of the 12
      SWI2 mutations that disrupt SWI2 activity in vivo alter the assembly of the
      SWI/SNF complex. These studies provide an invaluable framework for biochemical
      analysis of the SWI2 ATPase and for functional analysis of other SWI2 family
      members.

PMID- 8871546
TI  - Hydration of the RNA duplex r(CGCAAAUUUGCG)2 determined by NMR.
AB  - The so-called spine of hydration in the minor groove of AnTn tracts in DNA is
      thought to stabilise the structure, and kinetically bound water detected in the
      minor groove of such DNA species by NMR has been attributed to a narrow minor
      groove [Liepinsh, E., Leupin, W. and Otting, G. (1994) Nucleic Acids Res. 22,
      2249-2254]. We report here an NMR study of hydration of an RNA dodecamer which
      has a wide, shallow minor groove. Complete assignments of exchangeable protons,
      and a large number of non-exchangeable protons in r(CGCAAAUUUGCG)2 have been
      obtained. In addition, ribose C2'-OH resonances have been detected, which are
      probably involved in hydrogen bonds. Hydration at different sites in the
      dodecamer has been measured using ROESY and NOESY experiments at 11.75 and 14.1
      T. Base protons in both the major and minor grooves are in contact with water,
      with effective correlation times for the interaction of approximately 0.5 ns,
      indicating weak hydration, in contrast to the hydration of adenine C2H in the
      homologous DNA sequence. NOEs to H1' in the minor groove are consistent with
      hydration water present that is not observed in the analogous DNA sequence.
      Hydration kinetics in nucleic acids may be determined by chemical factors such as
      hydrogen-bonding more than by simple conformational factors such as groove width.

PMID- 8871547
TI  - An antibiotic-binding motif of an RNA fragment derived from the A-site-related
      region of Escherichia coli 16S rRNA.
AB  - A small RNA derived from the decoding region of Escherichia coli 16S rRNA can
      bind to antibiotics of aminoglycosides (neomycin and paromomycin) that act on the
      small ribosomal subunit [Purohit,P. and Stern,S. (1994) Nature, 370, 659-662]. In
      the present study, the P-site subdomain was removed from this decoding region RNA
      to construct a 27mer RNA (designated as ASR-27), which includes the A-site
      related region (positions 1402-1412 and 1488-1497) of 16S rRNA. Footprint
      experiments with dimethyl sulfate as a chemical probe indicated that the ASR-27
      RNA can interact with the neomycin family in the same manner as the decoding
      region RNA. A mutagenesis analysis of the ASR-27 RNA revealed that paromomycin
      binding of ASR-27 involves the C1407.G1494 and C1409-G1491 base pairs, and the
      internal loop comprising A1408 and the nucleotides in positions 1492-1493,
      located between the two C.G base pairs. In addition, a G or U in position 1495,
      and base pairing between positions 1405 and 1496 are also involved. These
      structural features were found in a viral RNA element, the Rev-binding site of
      human immunodeficiency virus type-1, which may explain why neomycin can bind to
      this viral RNA.

PMID- 8871548
TI  - A polyoma-based episomal vector efficiently expresses exogenous genes in mouse
      embryonic stem cells.
AB  - We describe the ability of novel episomally maintained vectors to efficiently
      promote gene expression in embryonic stem (ES) cells as well as in established
      mouse cell lines. Extrachromosomal maintenance of our vectors is based on the
      presence of polyoma virus DNA sequences, including the origin of replication
      harboring a mutant enhancer (PyF101), and a modified version of the polyoma early
      region (LT20) encoding the large T antigen only. Reporter gene expression from
      such extrachromosomally replicating vectors was approximately 10-fold higher than
      expression from replication-incompetent control plasmids. After transfection of
      different ES cell lines, the polyoma virus-derived plasmid variant pMGD20neo (7.2
      kb) was maintained episomally in 16% of the G418-resistant clones. No chromosomal
      integration of pMGD20neo vector DNA was detected in ES cells that contained
      episomal vector DNA even after long term passage. The vector's replication
      ability was not altered after insertion of up to 10 kb hprt gene fragments.
      Besides undifferentiated ES cells, the polyoma-based vectors were also maintained
      extrachromosomally in differentiating ES cells and embryoid bodies as well as in
      established mouse cell lines.

PMID- 8871549
TI  - Zn2+-sensing by the cyanobacterial metallothionein repressor SmtB: different
      motifs mediate metal-induced protein-DNA dissociation.
AB  - SmtB is a member of a family of repressors which dissociate from DNA in the
      presence of metals; Zn2+ being the most potent inducer of metallothionein gene
      (smtA) transcription in vivo. In Synechococcus PCC 7942 cells devoid of
      chromosomal smtB, four plasmid-encoded mutants of SmtB (C61S, T11S/C14S, C121S
      and H105R/H106R) repressed lacZ expression driven by the smtA operator-promoter.
      Gel retardation assays with extracts from the complemented cells detected
      multiple SmtB-dependent complexes similar to those obtained with extracts from
      wild-type cells or with recombinant-SmtB. Elevated [Zn2+] alleviated repression
      in vivo by all of the mutants except H105R/H106R. These His residues (one or
      both) are therefore essential for Zn2+-sensing while, contrary to expectations,
      Cys residues are not. Hence different motifs facilitate metal-induced DNA
      dissociation by SmtB and ArsR (the related oxyanion-sensing repressor),
      presumably generating variety in the spectra of metals sensed. Nucleotides and
      amino acids involved in DNA-SmtB interaction have been further defined/inferred
      and we also confirm that additional unknown factors form specific associations
      with the smt operator-promoter in elevated [Zn2+].

PMID- 8871551
TI  - Single-well genotyping of diallelic sequence variations by a two-color ELISA
      based oligonucleotide ligation assay.
AB  - Single nucleotide substitutions and unique insertions/deletions are the most
      common form of DNA sequence variation and disease-causing mutation in the human
      genome. Because of the biological and medical importance of these variations, a
      wide array of methods have been developed for their typing. We have applied an
      approach that combines the amplification of polymorphic regions by the polymerase
      chain reaction (PCR) with a system for typing diallelic variants using an
      oligonucleotide ligation assay (OLA). In this report, we describe a significant
      advance in this technology that permits the typing of two alleles in a single
      microtiter well. By marking each of the allele-specific primers with a unique
      hapten, i.e. digoxigenin and fluorescein, each OLA reaction can be detected by
      using hapten specific antibodies that are labeled with different enzyme
      reporters, alkaline phosphatase or horseradish peroxidase. This system permits
      the detection of the two alleles using a high throughput format that leads to the
      production of two different colors. We demonstrate the specificity, sensitivity
      and ease of data interpretation with this system. Furthermore, we show that
      multiplex PCR/OLA not only increases the throughput of DNA typing but also
      increases its accuracy in typing diallelic sequence variations using an approach
      that can be broadly applied for human genome analysis (in evaluating
      genotype/phenotype links), in typing infectious agents and in forensic analysis.

PMID- 8871550
TI  - Conserved thermochemistry of guanosine nucleophile binding for structurally
      distinct group I ribozymes.
AB  - We report thermodynamic values for binding of the guanosine nucleophile to the
      ribozyme derived from the Anabaena group I intron, and find that they are similar
      to those measured previously for the structurally distinct Tetrahymena ribozyme.
      The free energy of binding guanosine 5'-monophosphate (pG) at 30 degrees C is
      similar for the two ribozymes. The delta(H)degrees' and delta(S)degrees' for pG
      binding to the Anabaena ribozyme--RNA substrate complex (E x S) are 3.4 +/- 4
      kcal/mol and 27 +/- 10 e.u., respectively. The negligible enthalpic contribution
      and positive entropy change were found previously for the Tetrahymena ribozyme,
      and are considered remarkable for a hydrogen-bonding interaction between a
      nucleotide and a nucleic acid. These thermodynamic values may reflect
      conformational changes or water release upon pG binding that are comparable for
      the two ribozymes. In addition, the apparent chemical steps of the two ribozyme
      reactions share similar activation energies and a positive deltaS++. It now
      appears that such thermochemical values for guanosine binding and activation may
      be intrinsic properties of the group I intron catalytic center.

PMID- 8871552
TI  - A small circular TAR RNA decoy specifically inhibits Tat-activated HIV-1
      transcription.
AB  - Linear TAR RNA has previously been used as a decoy to inhibit HIV-1 transcription
      in vitro and HIV-1 replication in vivo. A 48 nucleotide circular RNA containing
      the stem, bulge and loop of the HIV-1 TAR element was synthesized using the self
      splicing activity of a group I permuted intron-exon and was tested for its
      ability to function as a TAR decoy in vitro. This small circular TAR molecule was
      exceptionally stable in HeLa nuclear extracts, whereas a similar linear TAR
      molecule was rapidly degraded. The TAR circle bound specifically to Tfr38, a
      peptide containing the TAR-binding region of Tat. The ability of Tat to trans
      activate transcription from the HIV-1 promoter in vitro was efficiently inhibited
      by circular TAR RNA but not by TAR circles that contained either bulge or loop
      mutations. TAR circles did not inhibit transactivation exclusively by binding to
      Tat since this inhibition was not reversed by adding excess Tat to the
      transcription reaction. Together, these data suggest that TAR circles act as
      decoys that inhibit transactivation by binding to Tat and at least one cellular
      factor. These data also demonstrate the utility of small circular RNA molecules
      as tools for biochemical studies.

PMID- 8871553
TI  - p72: a human nuclear DEAD box protein highly related to p68.
AB  - P72, a novel human member of the DEAD box family of putative RNA-dependent
      ATPases and ATP-dependent RNA helicases was isolated from a HeLa cDNA library.
      The predicted amino acid sequence of p72 is highly homologous to that of the
      prototypic DEAD box protein p68. In addition to the conserved core domains
      characteristic of DEAD box proteins, p72 contains several N-terminal RGG RNA
      binding domains and a serine/glycine rich C-terminus likely involved in mediating
      protein-protein interactions. A p72-specific probe detects two mRNAs of
      approximately 5300 and 9300 bases which, although ubiquitously expressed, show
      variability in their expression levels in different tissues. Purified recombinant
      p72 exhibits ATPase activity in the presence of a range of RNA moieties.
      Immunocytochemical studies of p68 and p72 show that these proteins localise to
      similar locations in the nucleus of HeLa cells, suggesting their involvement in a
      nuclear process.

PMID- 8871554
TI  - A convenient approach to the synthesis of trinucleotide phosphoramidites-
      synthons for the generation of oligonucleotide/peptide libraries.
AB  - Trinucleotide phosphoramidites that correspond to the codons of all 20 amino
      acids were synthesized in high yield in 5g scale. Precursors of those amidites-
      trinucleotide phosphotriesters--have been prepared using the phosphotriester
      approach without protection of the 3'-hydroxyl function. The structures of
      trinucleotide phosphotriesters and intermediates were confirmed by 1H- and 31P
      NMR spectra, mass-spectra and by analysis of SPDE-hydrolysates of deprotected
      preparations. Purity of the target products has been confirmed by test reactions.
      The synthons have been used for automated synthesis of oligonucleotides and
      corresponding libraries by a phosphite-triester approach. A 54mer, containing 12
      randomized internal bases, and a 72mer with 24 internal randomized bases have
      been synthesized.

PMID- 8871555
TI  - Identification of new RNA modifying enzymes by iterative genome search using
      known modifying enzymes as probes.
AB  - The complete nucleotide sequences of the Haemophilus influenzae and Mycoplasma
      genitalium genomes and the partially sequenced Escherichia coli chromosome were
      analyzed to identify open reading frames (ORFs) likely to encode RNA modifying
      enzymes. The protein sequences of known RNA modifying enzymes from three families
      -m5U methyltransferases, psi synthases and 2'-O methyltransferases--were used as
      probes to search sequence databases for homologs. ORFs identified as homologous
      to the initial probes were retrieved and used as new probes against the databases
      in an iterative manner until no more homologous ORFs could be identified. Using
      this approach, we have identified two new m5U methyltransferases, seven new psi
      synthases and four new 2'-O methyltransferases in E. coli. Many of the ORFs found
      in E.coli have direct genetic counterparts (orthologs) in one or both of
      H.influenzae and M.genitalium. Since there is a near-complete knowledge of RNA
      modifications in E.coli, functional activities of the proteins encoded by the
      identified ORFs were proposed based on the level of conservation of the ORFs and
      the modified nucleotides.

PMID- 8871556
TI  - Characterization of the DNA polymerase requirement of human base excision repair.
AB  - Base excision repair is one of the major mechanisms by which cells correct
      damaged DNA. We have developed an in vitro assay for base excision repair which
      is dependent on a uracil-containing DNA template. In this report, we demonstrate
      the fractionation of a human cell extract into two required components. One
      fraction was extensively purified and by several criteria shown to be identical
      to DNA polymerase beta (Polbeta). Purified, recombinant Polbeta efficiently
      substituted for this fraction. Escherichia coli PolI, mammalian Poldelta and to a
      lesser extent Polalpha and epsilon also functioned in this assay. We provide
      evidence that multiple polymerases function in base excision repair in human cell
      extracts. A neutralizing antibody to Polbeta, which inhibited repair synthesis
      catalyzed by pure Polbeta by approximately 90%, only suppressed repair in crude
      extracts by a maximum of approximately 70%. An inhibitor of Polbeta, ddCTP,
      decreased base excision repair in crude extracts by approximately 50%, whereas
      the Polalpha/delta/epsilon inhibitor, aphidicolin, reduced the reaction by
      approximately 20%. A combination of these chemical inhibitors almost completely
      abolished repair synthesis. These data suggest that Polbeta is the major base
      excision repair polymerase in human cells, but that other polymerases also
      contribute to a significant extent.

PMID- 8871558
TI  - Use of tagged random hexamer amplification (TRHA) to clone and sequence minute
      quantities of DNA--application to a 180 kb plasmid isolated from Sphingomonas
      F199.
AB  - We have developed a novel method to clone and sequence minute quantities of DNA.
      The method was applied to sequence a 180 kb plasmid pNL1. The first step was the
      production of a size distributed population of DNA molecules that were derived
      from the 180 kb plasmid pNL1. The first step was accomplished by a random
      synthesis reaction using Klenow fragment and random hexamers tagged with a T7
      primer at the primer 5'-end (T7-dN6, 5'-GTAATACGACTCACTATAGGGCNNNNNN-3'. In the
      second step, Klenow-synthesized molecules were amplified by PCR using T7 primer
      (5'-GTAATACGACTCACTATAGGGC-3'). With a hundred nanograms starting plasmid DNA
      from pNL1, we were able to generate Klenow-synthesized molecules with sizes
      ranging from 28 bp to >23 kb which were detectable on an agarose gel. The Klenow
      synthesized molecules were then used as templates for standard PCR with T7
      primer. PCR products of sizes ranging from 0.3 to 1.3 kb were obtained for
      cloning and sequencing. From the same Klenow-synthesized molecules, we were also
      able to generate PCR products with sizes up to 23 kb by long range PCR. A total
      232.5 kb sequences were obtained from 593 plasmid clones and over twenty putative
      genes were identified. Sequences from these 593 clones were assembled into 62
      contigs and 99 individual sequence fragments with a total unique sequence of 86.3
      kb.

PMID- 8871557
TI  - Viral transactivators E1A and VP16 interact with a large complex that is
      associated with CTD kinase activity and contains CDK8.
AB  - Previously, we showed that the viral transactivator proteins E1A and VP16
      specifically interact with a cellular CTD kinase activity in vitro. We now report
      that E1A and VP16 complexes contain human CDK8, a newly identified member of the
      cyclin-dependent kinase family that has been shown to be a component of the RNA
      polymerase II (RNAP II) holoenzyme complex. The presence of CDK8 in the E1A- and
      VP16-containing complexes is specific for a functional activation domain of these
      viral transactivators, strongly suggesting that this association is relevant for
      the transactivation function of E1A and VP16. We show that CDK8 is associated
      with CTD kinase activity and that CDK8 co-fractionates with E1A- and VP16
      associated CTD kinase activity over several chromatography columns. Therefore,
      CDK8 is likely responsible for the E1A- and VP16-associated CTD kinase activity.
      Gel filtration chromatography indicates that the E1A- and VP16-associated CTD
      kinase activity has a molecular size of approximately 1.5 MDa and contains cyclin
      C and the human homolog of SRB7 in addition to CDK8. This implies that E1A and
      VP16 associate with the RNAP II holoenyzme. We also looked at the transcriptional
      activity of CDK8 and found that CDK8 can function as a transcriptional activator
      when fused to the DNA binding domain of GAL4. Surprisingly, the ability of GAL4
      CDK8 to activate transcription in this assay was not dependent on the kinase
      activity of CDK8, since a kinase-deficient mutant of CDK8 stimulated
      transcription nearly as well as wild-type GAL4-CDK8. This suggests that CDK8 may
      play a role in transcription that is distinct from its ability to function as a
      CTD kinase.

PMID- 8871559
TI  - FLP-mediated recombination of FRT sites in the maize genome.
AB  - Molecular evidence is provided for genomic recombinations in maize cells induced
      by the yeast FLP/FRT site-specific recombination system. The FLP protein
      recombined FRT sites previously integrated into the maize genome leading to
      excision of a selectable marker, the neo gene. NPTII activity was not observed
      after the successful recombination process; instead, the gusA gene was activated
      by the removal of the blocking DNA fragment. Genomic sequencing in the region of
      the FRT site (following the recombination reaction) indicated that a precise
      rearrangement of genomic DNA sequences had taken place. The functional FLP gene
      could be either expressed transiently or after stable integration into the maize
      genome. The efficiency of genomic recombinations was high enough that a selection
      for recombination products, or for FLP expression, was not required. The results
      presented here establish the FLP/FRT site-specific recombination system as an
      important tool for controlled modifications of maize genomic DNA.

PMID- 8871560
TI  - Purification and biochemical analyses of a monomeric form of Tn5 transposase.
AB  - The binding of transposase (Tnp) to the specific Tn5 end sequences is the first
      dedicated reaction during transposition. In this study, comparative DNA-binding
      analyses were performed using purified full-length Tnp and a C-terminal deletion
      variant (delta369) that lacks the putative dimerization domain. The shape of the
      binding curve of full-length Tnp is sigmoidal in contrast to the hyperbolic
      shaped binding curve of delta369. This observation is consistent with previous
      observations as well as a rate of binding study presented here, which suggest
      that the full-length Tnp-end interaction, unlike that of the truncated protein,
      is a complex time-dependent reaction possibly involving a subunit exchange.
      Circular permutation assay results indicate that both proteins are capable of
      distorting the Tn5end sequences upon binding. Molecular weight determinations
      based on the migratory patterns of complexed DNA in polyacrylamide gels has shown
      that delta369 specifically binds the Tn5 end sequences as a monomer while full
      length Tnp in complex represents a heterodimer.

PMID- 8871562
TI  - Immobilized metal affinity chromatography of DNA.
AB  - Many of the most widely employed operations in molecular biology hinge upon the
      use of single-stranded DNA as a probe or template. Here we report a
      straightforward method by which to produce long single-stranded DNA molecules
      using the polymerase chain reaction (PCR) in combination with immobilized metal
      affinity chromatography (IMAC). We demonstrate that a tag consisting of six
      successive 6-histaminylpurine (H) residues (H6-tag) endows a DNA strand with
      selective retentivity onto a Ni2+-NTA-agarose chromatography matrix. The H6
      tagged strand can then be eluted from the resin using 200 mM imidazole.
      Quantitative phosphorimaging analysis revealed that the PCR/IMAC procedure
      typically yields unmodified strands comprising >90% of the unbound DNA and H6
      tagged strands comprising >95% of the bound fractions. DNA strands generated in
      this manner are shown to be excellent substrates for template-directed
      polymerization. The chemistry reported herein should facilitate a wide variety of
      operations in molecular biology, including automated DNA sequencing,
      hybridization screening of DNA libraries, assembly of gene cassettes, run-off
      transcription, site-directed mutagenesis and footprinting of protein-DNA
      complexes by template-directed interference footprinting.

PMID- 8871561
TI  - 3' Processing and termination of mouse histone transcripts synthesized in vitro
      by RNA polymerase II.
AB  - The highly expressed mouse histone H2a-614 gene is located 800 nt 5' of the
      histone H3-614 gene. There is a 140 nt sequence located 500 nt from the end of
      the H2-614 mRNA which has been defined as a transcription termination site for
      RNA polymerase II. We established an in vitro transcription system in which both
      3' end processing and transcription termination occur. A template containing the
      adenovirus major late promoter, a portion of the histone H2a-614 coding region,
      its 3' processing signal, followed by the transcription termination site was
      transcribed in a nuclear extract prepared from mouse myeloma cells. Some of the
      transcripts synthesized in the extract were cleaved at the histone processing
      site in a reaction which was dependent both on the hairpin binding factor and the
      U7 snRNP. The efficiency of histone 3' end formation was similar both on
      synthetic transcripts and transcripts synthesized by RNA polymerase II. Defined
      transcripts, which were not processed and which mapped to the transcription
      termination site, were released from the template, suggesting that they were
      formed by transcription termination. Termination in vitro was dependent on a
      functional histone processing signal.

PMID- 8871563
TI  - Solid support synthesis of all-Rp-oligo(ribonucleoside phosphorothioate)s.
AB  - The first method for solid support synthesis of all-Rp-oligo(ribonucleoside
      phosphorothioate)s is presented as well as attempts to increase the
      stereoselectivity of the key step in this approach. The synthetic strategy
      consists of (i) a solid support synthesis procedure, using 5'-O-(4
      methoxytriphenylmethyl)-2'-O-tert-butyldimethylsilyl-ri bon ucleoside 3'-H-
      phosphonates, that due to stereoselectivity in the condensation step, gives
      oligomers with mostly Sp-H-phosphonate diesters (72-89% under standard
      conditions), (ii) stereospecific sulfurization with S8 in pyridine to produce
      oligo(ribonucleoside phosphorothioate)s enriched with internucleosidic linkages
      of Rp configuration, (iii) treatment of the deprotected oligonucleotides with the
      enzyme Nuclease P1 from Penicillium citrinum, that specifically catalyses
      cleavage of Sp-phosphorothioate diester linkages, which leaves a mixture of
      oligomers having all internucleosidic linkages as Rp-phosphorothioates, and
      finally (iv) isolation and HPLC purification of the full length all-Rp oligomer.
      Mixed sequences containing the four common nucleosidic residues up to the chain
      length of a heptamer were synthesized. Change of N-4-protection on the cytidine
      building block from propionyl to N-methylpyrrolidin-2-ylidene gave a slightly
      improved diastereoselectivity in H-phosphonate diester formation. Increased
      selectivity up to 99+% was obtained with the guanosine building block when the
      amount of pyridine in the coupling step was reduced.

PMID- 8871564
TI  - The mouse poly(C)-binding protein exists in multiple isoforms and interacts with
      several RNA-binding proteins.
AB  - The murine poly(C)-binding protein (mCBP) was previously shown to belong to the
      group of K-homology (KH) proteins by virtue of its homology to hnRNP-K. We have
      isolated cDNA-splice variants of mCBP which differ by two variable regions of 93
      bp and/or 39 +/- 3 bp respectively. Both variable regions are located between the
      second and third KH-domain of mCBP. The characterization of a partial genomic
      clone enabled us to propose a model for the generation of the second variable
      region by the use of a putative alternative splice signal. The mCBP mRNA is
      expressed ubiquitously and the protein is found predominantly in the nucleus with
      the exception of the nucleoli. We have identified five proteins which interact
      with mCBP in the yeast two hybrid system: mouse y-box protein 1 (msy-1), y-box
      binding protein, hnRNP-L, filamin and splicing factor 9G8. The interaction
      between mCBP and splicing factor 9G8 was confirmed in vivo. These results suggest
      a function of mCBP in RNA metabolism.

PMID- 8871565
TI  - Structure, tissue distribution and genomic organization of the murine RRM-type
      RNA binding proteins TIA-1 and TIAR.
AB  - TIA-1 and TIAR are RNA binding proteins of the RNA recognition motif
      (RRM)/ribonucleoprotein (RNP) family that have been implicated as effectors of
      apoptotic cell death. We report the structures of murine TIA-1 and TIAR (mTIA-1
      and mTIAR) deduced from cDNA cloning, the mRNA and protein tissue distribution of
      mTIA-1 and mTIAR, and the exon-intron structures of the mTIA-1 and mTIAR genes.
      Both mTIA-1 and mTIAR are comprised of three approximately 100 amino acid N
      terminal RRM domains and a approximately 90 amino acid C-terminal auxiliary
      domain. This subfamily of RRM proteins is evolutionarily well conserved; mTIA-1
      and mTIAR are 80% similar to each other, and 96 and 99% similar to hTIA-1 and
      hTIAR, respectively. The overall exon-intron structures of the mTIA-1 and mTIAR
      genes are also similar to each other, as well as to the human TIA-1 gene
      structure. While Northern blot analysis reveals that mTIA-1 and mTIAR mRNAs have
      a broad tissue distribution, mTIA-1 and mTIAR proteins are predominantly
      expressed in brain, testis and spleen. At least two isoforms of both mTIA-1 and
      mTIAR are generated by alternative splicing. Murine TIA-1 isoforms including or
      lacking the exon 5 encoded sequences are expressed at a ratio of approximately
      1:1, whereas mTIAR isoforms including or lacking the 5'-end of exon 3 sequences
      are expressed in a approximately 1:6 ratio. Molecular characterization of murine
      TIA-1 and TIAR RNA binding proteins provides the basis for a genetic analysis of
      the functional roles of these proteins during mammalian development.

PMID- 8871567
TI  - Cloning and characterization of the genomic DNA of the human MSSP genes.
AB  - MSSP proteins have been identified by their binding to an upstream element of c
      myc. Independently, two different approaches yielded two cDNA clones highly
      homologous to the MSSP cDNAs, suggesting an involvement of MSSP in the regulation
      of the cell cycle (scr2) and in the repression of HIV-1 and ILR2 alpha-promoter
      transcription (human YC1). Screening human genomic libraries, we have isolated
      clones belonging to two different gene loci. Whereas the human MSSP gene 1 turned
      out to be intronless, the organization of the coding sequence within gene 2 is
      more complex. It spans more than 60 kb and contains 16 exons (including two
      alternative first exons), ranging from 48 to 287 bp, respectively. The intron
      sizes vary from 0.1 to more than 13 kb. Gene 1 has been completely sequenced. A
      deletion series of its upstream region was conjugated to the luciferase gene, but
      the transfection of the constructs did not display any promoter activity.
      Moreover, compared with gene 2 and the cDNA sequences known so far, about 20
      point mutations as well as flanking direct repeats have been detected in the MSSP
      gene 1, showing that it possesses all the characteristics of processed
      retropseudogenes. Sequence analysis of a 1.7 kb fragment of the 5' flanking
      region of the MSSP gene 2 revealed that the promoter of gene 2 lacks consensus
      sequences for TATA and CCAAT boxes, is GC-rich, and contains numerous potential
      transcription factor binding elements including an Sp1 binding site. DNase I
      footprinting experiments showed that the putative Sp1 site was bound by proteins.
      The results of primer extension and S1 mapping analyses suggested the
      transcription of the gene starts at multiple positions upstream from the
      initiator methionine codon. Luciferase assays employing progressive deletions of
      the 1.7 kb promoter region allowed us to define the minimal promoter region of
      428 bp (-488/+) and revealed a complex pattern of the transcriptional regulation
      the human MSSP gene 2. Furthermore, it can be concluded that the MSSP gene 2
      encodes both MSSP-1 and MSSP-2, and moreover scr2 and human YC1.

PMID- 8871566
TI  - Searching databases of conserved sequence regions by aligning protein multiple
      alignments.
AB  - A general searching method for comparing multiple sequence alignments was
      developed to detect sequence relationships between conserved protein regions.
      Multiple alignments are treated as sequences of amino acid distributions and
      aligned by comparing pairs of such distributions. Four different comparison
      measures were tested and the Pearson correlation coefficient chosen. The method
      is sensitive, detecting weak sequence relationships between protein families.
      Relationships are detected beyond the range of conventional sequence database
      searches, illustrating the potential usefulness of the method. The previously
      undetected relation between flavoprotein subunits of two oxidoreductase families
      points to the potential active site in one of the families. The similarity
      between the bacterial RecA, DnaA and Rad51 protein families reveals a region in
      DnaA and Rad51 proteins likely to bind and unstack single-stranded DNA. Helix-
      turn--helix DNA binding domains from diverse proteins are readily detected and
      shown to be similar to each other. Glycosylasparaginase and gamma
      glutamyltransferase enzymes are found to be similar in their proteolytic cleavage
      sites. The method has been fully implemented on the World Wide Web at URL:
      http://blocks.fhcrc.org/blocks-bin/LAMAvsearch.

PMID- 8871568
TI  - A new approach to overcome potassium-mediated inhibition of triplex formation.
AB  - G,A-containing purine oligonucleotides of various lengths form extremely stable
      and specific triplexes with the purine-pyrimidine stretch of the vpx gene
      [Svinarchuk,F., Monnot,M., Merle,A., Malvy,C. and Fermandjian,S. (1995) Nucleic
      Acids Res., 22, 3742--3747]. The potential application of triple-helix-forming
      oligonucleotides (TFO) in gene-targeted therapy has prompted us to study triplex
      formation mimicking potassium concentrations and temperatures in cells. Triplex
      formation was tested by dimethyl sulphate (DMS) footprinting, gel-retardation, UV
      melting studies and electron microscopy. In the presence of 10 mM MgCl2, KCl
      concentrations up to 150 mM significantly lowered both efficiency (triplex :
      initial duplex) and rate constants of triplex formation. The KCl effect was more
      pronounced for 11mer and 20mer TFOs than for 14mer TFO. Since the dissociation
      half-life for the 11mer TFO decreases from 420 min in the absence of monovalent
      cations to 40 min in the presence of 150 mM KCI, we suggest that the negative
      effect could be explained by a decrease in triplex stability. In contrast, for
      the 20mer TFO no dissociation of the triplex was observed during 24 h of
      incubation either in the absence of monovalent cations or in the presence of 150
      mM KCl. We suppose that in the case of the 20mer TFO the negative effect of KCI
      on triplex formation is probably due to the self-association of the
      oligonucleotide in competitive structures such as parallel duplexes and/or
      tetraplexes. This negative effect may be overcome by the prior formation of a
      short duplex either on the 3'- or 5'-end of the 20mer TFO. We refer to these
      partial duplexes as 'zipper' TFOs. It was demonstrated that a 'zipper' TFO can
      form a triplex over the full length of the target, thus unzipping the short
      complementary strand. The minimal single-stranded part of the 'zipper'
      oligonucleotide which is sufficient to initiate triplex formation can be as short
      as three nucleotides at the 3'-end and six nucleotides at the 5'-end. We suggest
      that this type of structure may prove useful for in vivo applications.

PMID- 8871569
TI  - Characterization of peptide-oligonucleotide heteroconjugates by mass
      spectrometry.
AB  - Two peptide-oligothymidylic acids, prepared by joining an 11 residue synthetic
      peptide containing one internal carboxyl group (Asp side chain) to amino-linker
      5'pdT6 and amino-linker-5'pdT10 oligonucleotides, were analyzed by matrix
      assisted laser desorption/ionization (MALDI) on a linear time-of-flight mass
      spectrometer and by electrospray ionization (ESI) on a triple-quadrupole system.
      These synthetic compounds model peptide-nucleic acid heteroconjugates encountered
      in antisense research and in studies that use photochemical crosslinking to
      investigate molecular aspects of protein-nucleic acid interactions. MALDI and ESI
      sensitivities for the two hybrid compounds were found to be similar respectively
      to their sensitivities for the pure oligonucleotide parts. In general, MALDI
      proved to be less affected by sample impurities and more sensitive than ESI,
      while ESI on the quadrupole produced greater mass accuracy and resolution than
      MALDI on the time-of-flight instrument. A hybrid's behavior in a MALDI-matrix or
      an ESI-spray-solvent was found to be governed mainly by the oligonucleotide. A
      single positive ESI tandem mass spectrum of the peptide-dT6 accounted for the
      heteroconjugate's entire primary structure including the point of the
      oligonucleotide's covalent attachment to the peptide.

PMID- 8871570
TI  - Gene transfer mediated by alpha2-macroglobulin.
AB  - alpha2-Macroglobulin covalently linked to poly(L)-lysine can be used as a vehicle
      for receptor-mediated gene transfer. This modified alpha2-macroglobulin maintains
      its ability to bind to the alpha2-macroglobulin receptor, and was shown to
      introduce a luciferase reporter gene plasmid into HepG2 human hepatoma cells in
      vitro. The alpha2-macroglobulin receptor is a very large and multifunctional cell
      surface receptor, whose rapid and efficient internalization rate makes it
      attractive for gene therapy, e.g. for hepatic gene targeting via injection into
      the portal vein.

PMID- 8871571
TI  - Temporal control of the Cre recombinase in transgenic mice by a tetracycline
      responsive promoter.
AB  - Gene-targeted mice derived from embryonic stem cells are a useful tool to study
      gene function during development. However, if the mutation is embryonic lethal
      and the gene is deleted from the onset of development, later functions in adult
      animals cannot be studied. Recently, the bacterial Cre-loxP site-specific
      recombination system has successfully been used in transgenic animals to produce
      tissue-specific and temporal deletions [Gu et al. (1993) Cell, 73, 1155"""""" Gu
      et al. (1994) Science, 265,103--106; Kuhn et al. (1995) Science, 269, 1427-1429].
      We have evaluated the tetracycline responsive binary system [Gossen and Bujard
      (1992) Proc. Natl. Acad. Sci. USA, 89, 5547-5551] for its ability to transiently
      express the Cre recombinase in transgenic mice. In this system, a transactivator
      fusion protein composed of the tetracycline repressor (tetR) and the acidic
      domain of the herpes simplex viral protein 16 (VP16) can regulate the expression
      of the Cre gene from a promoter containing tet-operator (tetO) sequences. In the
      absence of tetracycline, the Cre gene is expressed and will induce site-specific
      recombination between two loxP sites. In the presence of tetracycline, the Cre
      gene will not be expressed and recombination will not occur.

PMID- 8871572
TI  - Immunogenetics and heterogeneity in multiple sclerosis.

PMID- 8871573
TI  - Immunosuppressants, immunophilins, and the nervous system.

PMID- 8871574
TI  - Diagnostic guidelines in central nervous system Whipple's disease.
AB  - Many cases of central nervous system (CNS) Whipple's disease are not diagnosed
      until postmortem. Few reviews of CNS Whipple's disease have delineated the
      frequencies of abnormalities on neurological examination, cerebrospinal fluid
      studies, neuroimaging, and intestinal biopsy studies. Guidelines for diagnosis
      and treatment have not been proposed. In this review we present 3 new cases of
      CNS Whipple's disease and summarize the literature to determine the frequencies
      of neurological signs and abnormalities on diagnostic testing. We propose
      guidelines for diagnostic screening, selection for biopsy, and treatment. Review
      of the 84 cases of CNS Whipple's disease (81 in the literature, 3 new) revealed
      that 80% of the patients had systemic signs. Cognitive changes were frequent
      (71%), and 47% with cognitive changes also had psychiatric signs.
      Oculomasticatory myorhythmia and oculo-facial-skeletal myorhythmia, pathognomic
      for CNS Whipple's disease, were present in 20% of patients, and were always
      accompanied by a supranuclear vertical gaze palsy. Tissue biopsy was a sensitive
      technique; 89% of those who had biopsies had positive biopsy results. Diagnosis
      and treatment of definite CNS Whipple's disease should be based on the presence
      of pathognomic signs (oculomasticatory myorhythmia or oculo-facial-skeletal
      myorhythmia) or positive biopsy or polymerase chain reaction results. Possible
      CNS Whipple's disease should be diagnosed in the setting of unexplained systemic
      symptoms and neurological signs (supranuclear vertical gaze palsy, rhythmic
      myoclonus, dementia with psychiatric symptoms, or hypothalamic manifestations).
      Those with possible CNS Whipple's disease should undergo small-bowel biopsy.

PMID- 8871575
TI  - Western versus Asian types of multiple sclerosis: immunogenetically and
      clinically distinct disorders.
AB  - The polymorphism of HLA-DRB1, -DRB3, and -DRB5 genes as well as magnetic
      resonance images of the brain and spinal cord were studied in 57 Japanese
      patients with multiple sclerosis (MS). Twenty-three patients clinically displayed
      selective involvement of the optic nerve and spinal cord and were classified as
      having Asian-type MS. The other 34 patients had disseminated central nervous
      system involvement and were classified as having Western-type MS. Patients with
      Asian-type MS had fewer brain lesions shown by magnetic resonance imaging, but
      more gadolinium-enhanced spinal cord lesions than did patients with Western-type
      MS (47% vs 17%). Furthermore, the DR2-associated DRB1*1501 allele and DRB5*0101
      allele were associated with Western-type MS (41.2%), but not with either Asian
      type MS (0%) or healthy control subjects (14.2%). Heterogeneity in the
      immunogenetic background and in the magnetic resonance imaging features between
      the two subtypes of MS thus suggests the presence of two etiologically distinct
      diseases in Asians.

PMID- 8871576
TI  - Immunosuppression-induced leukoencephalopathy from tacrolimus (FK506)
AB  - Tacrolimus (FK506) has recently been approved for immunosuppression in organ
      transplantation, although its use is accompanied by a wide spectrum of neurotoxic
      side effects. We describe the clinical, radiological, and pathological features
      of 3 cases of tacrolimus-related leukoencephalopathy. The syndrome of
      immunosuppression-related leukoencephalopathy is proposed as an uncommon
      neurological syndrome occurring in patients with organ transplants involving
      demyelination, in particular in the parieto-occipital region and centrum
      semiovale. Although the syndrome is not associated with a particular (absolute)
      serum level of tacrolimus, it resolves spontaneously upon decreasing the dose.
      The tacrolimus-related syndrome has a similar radiographic and pathologic
      appearance as the analogous syndrome that occurs in patients taking cyclosporine.

PMID- 8871577
TI  - Inclusion body myositis: clinical and pathological boundaries.
AB  - Inclusion body myositis, polymyositis, and dermatomyositis are three distinct
      categories of inflammatory myopathy. Some authorities commented on the selective
      early weakness of the volar forearm muscles, quadriceps, and ankle dorsiflexors
      in inclusion body myositis. The most important feature distinguishing inclusion
      body myositis from the other two inflammatory myopathies is the lack of
      responsiveness to immunosuppressive treatment. Although most patients with
      inclusion body myositis have characteristic muscle biopsy findings, some cannot
      be distinguished histologically early from polymyositis. Predicting
      responsiveness to immunosuppressive medications, independent of muscle histology,
      would be valuable to clinicians. We retrospectively reviewed the pattern of
      weakness and other clinical features of 46 patients newly diagnosed with either
      inclusion body myositis, polymyositis, or dermatomyositis. Asymmetrical muscle
      weakness with prominent wrist flexor, finger flexor, and knee extensor
      involvement was specific for inclusion body myositis and unresponsive
      polymyositis. Male sex, lower creatine kinase levels, slower rate of progression,
      and peripheral neuropathy were also more common in inclusion body myositis and
      unresponsive polymyositis than in responsive polymyositis and dermatomyositis
      patients. Repeat muscle biopsy in 2 patients in the unresponsive polymyositis
      group demonstrated histological features of inclusion body myositis. We suspect
      that patients with clinical features of inclusion body myositis but lacking
      histological confirmation may nonetheless have inclusion body myositis. Our study
      supports the recently proposed criteria for definite and possible inclusion body
      myositis.

PMID- 8871578
TI  - Complement activation in the central nervous system following blood-brain barrier
      damage in man.
AB  - The central nervous system (CNS) is virtually isolated from circulating
      immunological factors such as complement (C), an important mediator of humoral
      immunity and inflammation. In circulation, C is constantly inhibited to prevent
      attack on host cells. Since a host of diseases produce an abnormal blood
      brain/cerebrospinal fluid (blood-brain/CSF) permeability allowing C protein
      extravasation, we investigated if C activation occurs in CSF in vitro and in CNS
      in vivo during subarachnoid hemorrhage (SAH) or brain infarction. After SAH (n =
      15), the terminal complement complex (TCC) concentration on days 0 to 2 was
      higher in the CSF, 210 +/- 61 ng/ml, than in the plasma, 63 +/- 17 ng/ml, but
      null in the CSF of controls (n = 8) or patients with an ischemic stroke (n = 7).
      TCC was eliminated from the CSF after SAH (24 +/- 10 ng/ml on days 7 to 10).
      Incubation of normal human CSF with serum in vitro also activated the terminal C
      pathway. In 10 fatal ischemic brain infarctions, immunohistochemical techniques
      demonstrated neuronal fragment-associated deposition of C9 accompanied by
      neutrophil infiltration. We conclude that the C system becomes activated
      intrathecally in SAH and focally in the brain parenchyma in ischemic stroke. By
      promoting chemotaxis and vascular perturbation, C activation may instigate
      nonimmune inflammation and aggravate CNS damage in diseases associated with
      plasma extravasation.

PMID- 8871579
TI  - Trifunctional enzyme deficiency: adult presentation of a usually fatal beta
      oxidation defect.
AB  - Disorders of mitochondrial fatty acid oxidation are a common cause of exercise
      induced rhabdomyolysis and myoglobinuria. We report three adult patients from a
      family with symptoms of recurrent exercise-induced rhabdomyolysis. This
      presentation closely resembles adult-type carnitine palmitoyltransferase II
      deficiency except that these patients had an associated peripheral neuropathy.
      Investigation of fatty acid oxidation in the patients revealed a deficiency of
      the mitochondrial trifunctional enzyme of beta-oxidation, a newly described fatty
      acid oxidation disorder with multiorgan involvement and a usually fatal outcome
      in early childhood. Our cases therefore represent a new phenotype of the disease,
      which is characterized by recurrent rhabdomyolysis and peripheral neuropathy, but
      without involvement of other organs, and which is associated with prolonged
      survival beyond the fourth decade. A low-fat/high-carbohydrate diet proved
      beneficial in one of the patients, drastically reducing the frequency of
      rhabdomyolytic episodes. Our findings suggest that mitochondrial trifunctional
      enzyme deficiency should be considered in patients with recurrent episodes of
      myoglobinuria and peripheral neuropathy presenting in later life.

PMID- 8871580
TI  - Sequence variants in human neurofilament proteins: absence of linkage to familial
      amyotrophic lateral sclerosis.
AB  - Neurofilaments, assembled from NF-L (68 kd), NF-M (95 kd), and NF-H (115 kd), are
      the most abundant structural components in large myelinated axons, particularly
      those of motor neurons. Aberrant neurofilament accumulation in cell bodies and
      axons of motor neurons is a prominent pathological feature of several motor
      neuron diseases, including sporadic and familial amyotrophic lateral sclerosis
      (ALS). Transgenic methods have proved in mice that mutation in or increased
      expression of neurofilament subunits can be primary causes of motor neuron
      disease that mimics the neurofilamentous pathology often reported in human
      disease. To examine whether mutation in neurofilament subunits causes or
      predisposes to ALS, we used single-strand conformation polymorphism coupled with
      DNA sequencing to search for mutations in the entirety of the human NF-L, NF-M,
      and NF-H genes from 100 familial ALS patients known not to carry mutations in
      superoxide dismutase 1 (SOD1), as well as from 75 sporadic ALS patients. Six
      polypeptide sequence variants were identified in rod and tail domains of NF-L, NF
      M, or NF-H. However, all were found at comparable frequency in DNAs from normal
      individuals and no variant cosegregated with familial disease. Two deletions
      found previously in NF-H genes of sporadic ALS patients were not seen in this
      group of familial or sporadic ALS patients.

PMID- 8871581
TI  - HIV-1 DNA in brains in AIDS and pre-AIDS: correlation with the stage of disease.
AB  - Seventeen asymptomatic individuals positive for human immunodeficiency virus type
      1 (HIV-1) and 16 patients with acquired immunodeficiency syndrome (AIDS), all
      with polymerase chain reaction evidence of HIV-1 DNA, were selected for
      quantitative analysis to correlate the levels of HIV-1 DNA in brain tissue with
      the stage of infection. The AIDS patients either were clinically asymptomatic or
      presented various abnormalities. Neuropathological lesions were assessed by
      morphological and immunohistochemical methods. To determine the level of HIV-1
      DNA, semiquantitative nested polymerase chain reaction was applied using a
      digoxigenin-labeled primer and chemiluminescence. Serial dilutions of standard
      HIV DNA were run in parallel with brain DNA samples. Among the 16 AIDS brains
      studied, 9 showed changes characteristic of HIV encephalitis/leukoencephalopathy
      while 1 showed focal pontine leukoencephalopathy and 6 showed no obvious
      neuropathological lesions. Abnormalities in pre-AIDS individuals included
      meningitis, microgliosis, and astrogliosis. Copy numbers of HIV-1 DNA in the
      brains of AIDS patients were higher than those in asymptomatic individuals
      (median, 135 vs 45 copies/150,000 cells). However, there was some degree of
      overlapping between the two groups, with some AIDS patients showing low figures
      while 3 asymptomatic individuals had high copy numbers. This suggests that the
      use of HIV-1 DNA load in the central nervous system as an indicator of
      progression of the disease should be restricted to large series and not single
      patients.

PMID- 8871582
TI  - Interferon beta induces interleukin-10 expression: relevance to multiple
      sclerosis.
AB  - Interferon-beta decreases the relapse rate, relapse severity, progression of
      neurological disability, and development of new brain lesions observed with brain
      magnetic resonance imaging in relapsing-remitting multiple sclerosis patients.
      The mechanism of action of this effect is presently unknown. This study was based
      on the hypothesis that immunoregulatory effects of interferon-beta may underlie
      its demonstrated clinical efficacy. The objective of the study was to determine
      the effect of interferon-beta-1a on the expression of interleukin-10, a cytokine
      that strongly inhibits cell-mediated immune responses. Interferon-beta-1a induced
      accumulation of interleukin-10 messenger RNA and protein secretion by cultured
      peripheral blood mononuclear cells. The observed in vitro effects were similar
      for healthy control subjects and multiple sclerosis patients. Intramuscular
      injections of interferon-beta-1a increased serum levels of interleukin-10 at 12
      and 24 hours following the injection. Greater increases were induced with 12 x
      10(6)-IU than 6 x 10(6)-IU injections. The effect of interferon-beta-1a was
      relatively specific for interleukin-10, as treatment with interferon-beta-1a did
      not result in accumulation of transforming growth factor-beta messenger RNA.
      Upregulation of interleukin-10 represents a possible mechanism of action of
      interferon-beta's therapeutic effect in relapsing-remitting multiple sclerosis,
      and has implications for therapy of other autoimmune diseases.

PMID- 8871583
TI  - Speech-induced changes in corticospinal excitability.
AB  - The aim of the experiments was to investigate the effects of speech on the
      excitability of corticospinal pathways to human hand muscles. Single transcranial
      magnetic stimuli were given randomly over the hand area of either the left or
      right motor cortex of 10 right-handed and 3 left-handed normal volunteers.
      Electromyographic responses were recorded in the relaxed first dorsal
      interosseous muscle while the subjects (a) read aloud a piece of text, (b) read
      silently, (c) spoke spontaneously, or (d) made sounds without speaking. The only
      consistent effect across subjects occurred during task a, which significantly
      increased the size of responses evoked in the dominant hand of all subjects, but
      had either no effect (8 subjects) or a smaller effect in the nondominant hand.
      Tasks b and d had no reliable effect, whereas task c tended to increase response
      size in both hands. Control measurements suggest that the effects in task a were
      caused by changes in cortical rather than spinal excitability. This is the first
      demonstration of lateralized speech effects on the excitability of cortical arm
      areas. The results provide a useful adjunct to other tests of cerebral dominance,
      using only single- rather than repetitive-pulse cortical stimulation.

PMID- 8871584
TI  - Acute motor axonal neuropathy: an antibody-mediated attack on axolemma.
AB  - The acute motor axonal neuropathy (AMAN) form of the Guillain-Barre syndrome is a
      paralytic disorder of abrupt onset characterized pathologically by motor nerve
      fiber degeneration of variable severity and by sparing of sensory fibers. There
      is little demyelination or lymphocytic inflammation. Most cases have antecedent
      infection with Campylobacter jejuni and many have antibodies directed toward GM1
      ganglioside-like epitopes, but the mechanism of nerve-fiber injury has not been
      defined. In 7 fatal cases of AMAN, immunocytochemistry demonstrated the presence
      of IgG and the complement activation product C3d bound to the axolemma of motor
      fibers. The most frequently involved site was the nodal axolemma, but in more
      severe cases IgG and C3d were found within the periaxonal space of the myelinated
      internodes, bound to the outer surface of the motor axon. These results suggest
      that AMAN is a novel disorder caused by an antibody- and complement-mediated
      attack on the axolemma of motor fibers.

PMID- 8871585
TI  - Acute myopathy of intensive care: clinical, electromyographic, and pathological
      aspects.
AB  - An acute myopathy of intensive care occurs in critically ill patients treated
      with intravenous corticosteroids and neuromuscular junction-blocking agents. The
      full clinicopathological spectrum is uncertain. We evaluated the clinical,
      electrodiagnostic, and histopathological features of 14 patients who developed
      acute myopathy of intensive care after organ transplantation or during treatment
      of severe pulmonary disorders and sepsis. Patients received high-dose intravenous
      corticosteroids, usually in conjunction with relatively low to moderate doses of
      neuromuscular junction-blocking agents. After discontinuation of the latter
      drugs, most had diffuse, flaccid weakness with failure to wean from mechanical
      ventilation. Electrodiagnostic findings were consistent with a necrotizing
      myopathy. Muscle histopathology revealed myopathy with loss of thick filaments in
      79%, mild myopathic changes in 14%, and atrophy of type 1 and type 2 fibers in
      7%. Loss of thick filaments was identified in muscle biopsy specimens obtained 30
      +/- 11 days (mean +/- standard deviation) after intravenous corticosteroid
      treatment but not in those obtained earlier (12 +/- 2 days). Critically ill
      patients, including those receiving organ transplants, may develop acute myopathy
      of intensive care after exposure to intravenous corticosteroids and neuromuscular
      junction-blocking agents, although the exposure to the latter drugs may be
      minimal. Selective loss of thick filaments is common in acute myopathy of
      intensive care, especially if the muscle biopsy specimen is obtained 2 weeks or
      more after intravenous corticosteroid exposure.

PMID- 8871586
TI  - Exercise fuel mobilization in mitochondrial myopathy: a metabolic dilemma.
AB  - In mitochondrial myopathy, severely impaired muscle oxidative capacity poses a
      dilemma for metabolic regulation in exercise. We inquired whether fuel
      mobilization during exercise in mitochondrial myopathy is adjusted to the reduced
      capacity to oxidize substrate, or if fuel is mobilized in excess of oxidative
      capacity. Hormonal and metabolic responses to 20 minutes of cycle exercise were
      studied in 4 patients with mitochondrial myopathy working at near maximal effort
      and in 4 healthy matched controls. On 2 separate days, controls were studied at
      the same absolute (A) workload (9 +/- 3 W) and the same relative (R) workload (77
      +/- 9 W) as performed by the patients. During exercise, average glucose
      production was higher in patients (28 +/- 5 micromol min(-1) kg(-1)) than in
      controls at both workloads (A, 12 +/- 1; R, 18 +/- 2 micromol min(-1) kg(-1)).
      Exercise-induced increases in plasma glucose, growth hormone, epinephrine,
      norepinephrine, corticotropin, and lactate, and decreases in plasma insulin and
      pH were also larger in patients compared with findings in controls at both
      workloads. In conclusion, mitochondrial myopathies are associated with excessive
      neuroendocrine responses and mobilization of glucose during exercise. These
      responses augment ATP synthesis but result in progressive accumulation of
      nonoxidized substrates. Apparently, substrate mobilization and neuroendocrine
      responses in exercise are linked to oxidative demand rather than to oxidative
      capacity in working muscle.

PMID- 8871587
TI  - Origin and functional consequences of the complex I defect in Parkinson's
      disease.
AB  - The mitochondrial electron transport enzyme NADH:ubiquinone oxidoreductase
      (complex I), which is encoded by both mitochondrial DNA and nuclear DNA, is
      defective in multiple tissues in persons with Parkinson's disease (PD). The
      origin of this lesion and its role in the neurodegeneration of PD are unknown. To
      address these questions, we created an in vitro system in which the potential
      contributions of environmental toxins, complex I nuclear DNA mutations, and
      mitochondrial DNA mutations could be systematically analyzed. A clonal line of
      human neuroblastoma cells containing no mitochondrial DNA was repopulated with
      mitochondria derived from the platelets of PD or control subjects. After 5 to 6
      weeks in culture, these cytoplasmic hybrid (cybrid) cell lines were assayed for
      electron transport chain activities, production of reactive oxygen species, and
      sensitivity to induction of apoptotic cell death by 1-methyl-4-phenyl pyridinium
      (MPP+). In PD cybrids we found a stable 20% decrement in complex I activity,
      increased oxygen radical production, and increased susceptibility to 1-methyl-4
      phenyl pyridinium-induced programmed cell death. The complex I defect in PD
      appears to be genetic, arising from mitochondrial DNA, and may play an important
      role in the neurodegeneration of PD by fostering reactive oxygen species
      production and conferring increased neuronal susceptibility to mitochondrial
      toxins.

PMID- 8871588
TI  - Clinically distinct codon 69 mutations in major myelin protein zero in
      demyelinating neuropathies.
AB  - Mutations in the major peripheral myelin protein zero (P0) gene on chromosome
      1q21-q23 have been found with the hereditary demyelinating polyneuropathy Charcot
      Marie-Tooth type 1B. Here, we describe 2 patients with distinct neurological
      characteristics, carrying different substitutions at the same codon--Arg69His and
      Arg69Cys. The patients were heterozygous for the mutation, which in both appeared
      to be de novo. Histological examination of sural nerve biopsy specimens revealed
      defective myelin as well as marked differences, confirming the importance of P0
      in the compaction of myelin.

PMID- 8871589
TI  - Cognitive and brain magnetic resonance imaging findings in adrenomyeloneuropathy.
AB  - Neuropsychological functioning and brain magnetic resonance imaging (MRI) were
      evaluated in 84 men with adrenomyeloneuropathy (AMN). MRI was normal in 61%, the
      "pure AMN" group, while 39%, the "cerebral AMN" group, showed brain white matter
      abnormalities. Except for mild deficits in psychomotor speed and visual memory,
      neuropsychological function was normal in pure AMN. Most patients with cerebral
      AMN had normal IQ and language but evidenced impaired psychomotor speed, spatial
      cognition, memory, and executive functions. Patients with MRI evidence of very
      severe cerebral disease had global and language impairment as well, and deficits
      in all patients were highly correlated with degree of brain MRI involvement.

PMID- 8871590
TI  - Apolipoprotein E and alpha1-antichymotrypsin polymorphism in Alzheimer's disease.
AB  - A recent observation has shown that a common polymorphism in the alpha1
      antichymotrypsin (ACT) gene modifies the apolipoprotein E (ApoE) epsilon4
      associated Alzheimer's disease (AD) risk identifying the combination of the
      ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker
      for AD. We analyzed the segregation of the ApoE and ACT polymorphism in sporadic
      and familial AD patients. In none of the sporadic AD patients did we find the
      combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes. The frequency of
      ApoE epsilon4/epsilon4 homozygosity in the AD sample resulted highest for the
      ACT/ TT genotype (17.6%). Our data fail to confirm any additional association
      with AD beyond the ApoE epsilon4 allele with any ACT genotype, suggesting that
      ACT does not represent an additional risk factor for AD.

PMID- 8871591
TI  - Exclusion of the DYT1 locus in familial torticollis.
AB  - Clinical-genetic studies of idiopathic torsion dystonia (ITD) indicate that the
      DYT1 gene on chromosome 9q34 is responsible for most childhood limb-onset
      disease. The genetic basis of adult-onset ITD is less well studied. In most
      multiplex adult-onset ITD families, dystonia is limited to the cervical, cranial,
      or brachial muscles; in a few rare families, dystonia also involves the legs and
      trunk. Previous linkage studies have excluded the DYT1 locus in these atypical
      families. We studied two large non-Jewish families with adult-onset ITD limited
      to the cervical and brachial muscles and excluded the DYT1-containing region.
      This study further restricts the role of DYT1 to childhood limb-onset ITD and
      suggests that other genes are responsible for focal adult-onset ITD.

PMID- 8871592
TI  - Episodic ataxia and myokymia syndrome: a new mutation of potassium channel gene
      Kv1.1.
AB  - Episodic ataxia and myokymia syndrome is an autosomal dominant disorder
      characterized by persistent myokymia and attacks of unsteadiness, slurred speech,
      and tremulousness. This disease has been associated with point mutations in the
      potassium channel gene Kv1.1 (KCNA1), located at chromosome 12p13. Here, we
      describe a novel mutation within this gene in a newly diagnosed family.

PMID- 8871593
TI  - Clinical correlates of apolipoprotein E in Alzheimer's disease.

PMID- 8871594
TI  - CNS distribution of free-radical inactivating enzymes in amyotrophic lateral
      sclerosis.

PMID- 8871595
TI  - Role of natural killer cells in the generation of influenza virus-specific
      cytotoxic T cells.
AB  - Recently we reported that natural killer (NK) cells are critical accessory cells
      required for the differentiation of alloantigen-stimulated CD8+ T cells into
      effector cytotoxic T lymphocytes (CTL) in vitro. In this study we provide
      evidence that NK cells are also required for the generation of influenza virus
      specific CTL. Depletion of NK cells from responder human peripheral blood
      mononuclear cells or mouse splenocytes abolished the induction of influenza A
      virus-specific CTL under culture conditions. Treatment of C57BL/6 mice with the
      NK cell-depleting NK1.1 monoclonal antibody (mAb) before primary or secondary
      immunization with influenza A virus abrogated the capacity of CTL precursors to
      differentiate into influenza virus-specific CTL effectors in vivo. These results
      extend our previous findings and demonstrate that NK cells critically influence
      the induction of antigen-specific CTL, both in vitro and in vivo.

PMID- 8871596
TI  - MHC class II-mediated T cell response to DNA.
AB  - Anti-DNA antibodies are elevated in several autoimmune diseases, including
      systemic lupus erythematosus. Yet, DNA was not shown to be presented by molecules
      of the major histocompatibility complex (MHC), nor was it reported to
      specifically stimulate T cells in vivo, although these steps are essential for
      antibody production. We now demonstrate DNA-specific T cell activation, which
      involves presentation of DNA by MHC class II molecules. T cells, isolated from
      lymph nodes of mice immunized with a murine monoclonal anti-anti-DNA antibody,
      proliferated in response to DNA. Moreover, presentation of DNA by murine antigen
      presenting cells could be inhibited with an isotype-specific anti-Ia antibody,
      and with peptides restricted by the same H-2 haplotype, suggesting that it is MHC
      class II-mediated. These results indicate that DNA can play a direct role in the
      regulation of T cells and in autoimmune processes.

PMID- 8871597
TI  - Interaction between the extracellular domain of CD7 and concanavalin A: a clue to
      the identity of the ligand for CD7.

PMID- 8871598
TI  - Immunosuppression by YAC-1 lymphoma: role of shed gangliosides.
AB  - Shedding of gangliosides from tumor cells may regulate immune responses in
      cancer. A major mechanism of T-cell immunosuppression by gangliosides in vitro
      entails blocking of the interaction of interleukin-2 (IL-2) with its receptor;
      however, its involvement in immune suppression by gangliosides shed by tumor
      cells is not known. A model system was developed for assessing inhibition of IL-2
      stimulated T-cell proliferation by components shed from murine YAC-1 lymphoma.
      Gangliosides shed by YAC-1 into the culture medium were present mainly in
      micellar form. YAC-1 supernatant suppressed both DNA synthesis and cellular
      growth in HT-2, while DNA synthesis in lymphokine-independent cell lines was
      unaffected. The immunosuppressive activity of YAC-1 supernatant was evident early
      in the IL-2 signaling pathway, and it had no permanent effect on proliferative
      capacity of the cells. Inhibition of DNA synthesis was reversed by high levels of
      IL-2, and YAC-1 supernatants blocked binding of [125I]IL-2 to high-affinity IL-2
      receptors. Taken together, these data suggest that one mechanism by which
      ganglioside micelles shed from YAC-1 exert their immunosuppressive effects on T
      cells involves blocking the IL-2/IL-2 receptor system.

PMID- 8871599
TI  - Natural killer cell recognition of "self" and "non-self" triggering antigens on
      normal lymphoblasts.
AB  - NK cell specificity for normal lymphoblasts was tested in mice by direct
      cytotoxicity and competitive inhibition assays. IL-2-activated NK cells lysed Hh
      1 incompatible but not Hh-1 compatible or Hh-1[null] allogeneic and semisyngeneic
      lymphoblasts. NK cells also lysed some syngeneic blasts. NK alloreactivity was
      inhibited by unlabeled targets which shared at least one Hh-1 determinant with
      the labeled target. NK self-reactivity was inhibited by syngeneic cells as well
      as by some allogeneic cells. Class I molecule-deficient beta2m-/- blasts
      universally inhibited NK lysis of all normal blasts. Cold targets appeared to
      specifically inhibit NK lysis by competing for recognition by NK activatory
      receptors rather than by competing for NK lysis by sharing with hot targets the
      absence of MHC class I inhibitory molecules recognized by NK cell Ly49 molecules.
      Backcross analysis revealed that a single non-MHC-linked gene locus regulates the
      accessibility of some normal lymphoblast target antigens to recognition by
      triggering receptors on self-reactive BALB/c NK cells. The results suggest that
      target lymphoblast class I molecules may differentially control the accessibility
      of universally expressed polymorphic NK triggering antigens to positive
      recognition by distinct sets of alloreactive and self-reactive NK cells.

PMID- 8871600
TI  - Extrathymic development of self-reactive gamma(delta) T cells in athymic BALB/c
      nu/nu mice.
AB  - In the present report, we demonstrated that extrathymic gamma(delta) T cells
      proliferated in the mixed culture of lymph node cells of BALB/c nu/nu mice and
      irradiated syngeneic spleen cells (syngeneic MLR). Reverse transcription
      polymerase chain reaction (RT-PCR) analyses revealed that V(delta)5 and V(delta)6
      were dominantly expressed by the gamma(delta) T cells from the syngeneic MLR.
      Furthermore, the syngeneic MLR may expand V(delta)5+ T cells with BALB invariant
      delta (BID) sequence which is specifically detected in BALB background mice
      because V(delta)5 RT-PCR products from syngeneic MLR were digested with an AluI
      restriction enzyme which cut the D(delta)2-J(delta)1 junction of the BID sequence
      but not those of most non-BID V(delta)5 sequences. Interestingly, anti
      mycobacterial and mammalian heat shock protein (Hsp) 60 mAb ML30 suppressed the
      generation of V(delta)5 with an AluI site in syngeneic MLR. These results suggest
      that extrathymically derived V(delta)5+ and V(delta)6+ gamma(delta) T cells
      recognize BALB/c self antigens and that the Hsp60 or an Hsp60-related molecule
      may be involved in the anti-self response of V(delta)5+ BID+ gamma(delta) T
      cells.

PMID- 8871601
TI  - The effect of a selective estrogen receptor modulator on the progression of
      spontaneous autoimmune disease in MRL lpr/lpr mice.
AB  - The MRL lpr/lpr mouse strain is an animal model for the autoimmune disorder
      systemic lupus erythematosus (SLE). Pathologic changes in the mice include a
      severe proliferative glomerulonephritis, lymph node and spleen enlargement,
      increase in autoantibody titers, and shortened life spans. In the present
      investigation, female MRL lpr/lpr mice have been dosed po daily for 7 months with
      the selective estrogen receptor modulator (SERM) LY139478 (4 mg/kg) or 17alpha
      ethinylestradiol (EE2, 1 mg/kg) and compared to vehicle control animals. The
      LY139478 group had an increase in survival (73% survival at 7 months, P = 0.02)
      but the EE2-treated animals did not (53% survival at 7 months, P = 0.4) when
      compared to the control group (32% survival at 7 months). Although there were no
      reductions in autoantibody levels as determined by anti-DNA antibody ELISA,
      histological analysis of kidney tissue indicated that both LY139478 and EE2
      mitigated the progression of glomerular nephritis which was evident in the
      controls. In contrast, there were no significant differences in lymph node size
      although the LY139478 and EE2 groups retained a well-defined sinusoidal region.
      Finally, flow cytometric analysis documented that thymuses from animals treated
      for 7 months with LY139478 but not with EE2 contained predominantly CD4+/CD+ T
      cells consistent with a normal thymic phenotype observed in non-MRL lpr/lpr mouse
      strains. These studies demonstrate that SERMs may be potentially useful for the
      treatment of autoimmune disorders.

PMID- 8871602
TI  - Reversal of age-related deficient influenza virus-specific CTL responses and IFN
      gamma production by monophosphoryl lipid A.
AB  - Old and young Balb/c mice, 24--26 and 2--4 months old, respectively, were
      infected with a 0.1 LD50 of influenza A/Taiwan/1/86 (A/H1N1) virus by small
      particle aerosol. Lung virus titers were determined 4, 6, 8, 12, and 17 days
      later. Old mice had significantly higher virus titers than young mice (P < 0.05
      0.0001) and shed virus up to Day 17, while young mice were free of virus by Day
      12. Splenic MHC class I CD8+ CTL activity (P < 0.08--0.001) and IFN-gamma
      production (0.1-0.008) measured on Days 8, 12, and 17 were significantly lower
      among old mice than among young mice. Coadministration of liposomal influenza
      vaccine with monophosphoryl lipid A (MPL) resulted in enhanced CD8+ CTL response
      and IFN-gamma production among old mice (35 and 12,000 times, respectively).
      These results demonstrate that MPL stimulates CTL and Th1 cytokines (IFN-gamma)
      in aged mice and may serve to reverse age-related CD8+ CTL deficiency and reduce
      severe influenza disease in elderly human populations.

PMID- 8871603
TI  - Anergy induction in human CD4+ T-cell clones by stimulation with soluble peptides
      does not require cell proliferation and is accompanied by elevated IL4
      production.
AB  - The stimulation of activated T cells with soluble peptides or peptide-pulsed T
      APC in the absence of professional APC can anergize peptide-specific T cells.
      Here, we studied human T cell clones (TCCs) that either proliferate (T-responder)
      or do not proliferate (T-nonresponder) to activated T cells as antigen-presenting
      cells (APC) and investigated the efficacy of anergy induction in these two types
      of TCCs. The TCCs were specific to the p30 peptide from tetanus toxoid and
      secreted either a Th0- or a Th1-like cytokine pattern. To induce anergy, the TCCs
      were first stimulated by addition of the peptides directly to the cell cultures
      without additional APC (T-APC). Anergy was detected by restimulating these TCCs
      on professional B-APC. The proliferation, production of cytokines (IL2, IFN
      gamma, IL4, IL5, IL10), and the cytotoxicity were measured after the first and
      second stimulation and compared with nonanergized control cells. Priming of TCCs
      by T-APC (anergy induction) resulted in an elevated production of IL4. This
      cytokine shift was also seen in the T-nonresponder TCC despite no induced
      proliferation. Th1-like TCCs retained their cytotoxicity after anergy induction.
      In contrast to cells first activated by B-APC, the restimulation of TCCs primed
      by T-APC lead to a drastic reduction of proliferation and cytokine production for
      both T-responder and T-nonresponder TCCs. The functional down-regulation of TCCs
      mediated by soluble peptides could be overcome by addition of IL2, but not by IL1
      or IL4. We concluded that the induction of T-cell anergy does not require cell
      proliferation.

PMID- 8871604
TI  - The mechanism of interleukin 4-induced down-regulation of CD38 on human B cells.
AB  - Exposure of Farage, a human B-cell line, to interleukin 4 (IL4) reduced the
      amount of CD38 antigen on the surface of the cells and in cell lysates. No
      evidence was obtained for accelerated breakdown, shedding, or internalization of
      CD38 molecules following IL4 treatment, nor the accumulation of CD38 molecules in
      the cell interior. The inhibition of protein synthesis with cycloheximide (CXM)
      diminished the down-regulation of CD38 induced by IL4. CXM decreased the
      expression of CD38 in Farage cells with arrested mitosis, and IL4 failed to
      further reduce CD38 expression. Staurosporine, an inhibitor of serine/threonine
      protein kinases, and H7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine), a
      preferential inhibitor of protein kinase C (PKC), abrogated the effect of IL4 on
      CD38, while inhibitors of other serine protein kinases W7 (N-(aminohexyl)-5
      chloro-1-naphthalenesulfoamide) and H8 (N-(2-[methylamino]ethyl)-5
      isoquinolinesulfonamide) failed to interfere with the effect of IL4. Phorbol 12
      myristate 13-acetate (PMA), an activator of PKC, resembled IL4 in decreasing the
      expression of CD38, and either staurosporine or H7 abolished this effect.
      Genistein, an inhibitor of tyrosine kinases, increased the expression of CD38,
      but failed to abrogate the inhibitory effect of IL4 on CD38. It is concluded that
      serine/threonine protein kinases mediated the IL4-induced down-regulation of the
      expression of CD38 molecules in B cells.

PMID- 8871605
TI  - Characterization of in vivo primary and secondary CD8+ T cell responses induced
      by recombinant influenza and vaccinia viruses.
AB  - We characterized the in vivo primary and secondary murine CD8+ T cell responses
      induced by immunization with influenza and vaccinia viruses, which were
      engineered to express the same H-2K(k)- and H-2K(d)-restricted epitopes. Our
      results show that the induction and magnitude of the primary CD8+ T cell response
      closely depends on the viral dose used for immunization, while it is not affected
      by the route of immunization. The induction of secondary CD8+ T cell responses
      appears to be highly restricted, as suggested by the lack of in vivo expansion of
      antigen-specific CD8+ T cells after repeated immunization with the same virus. In
      contrast, a 20- to 30-fold increase in the frequency of antigen-specific CD8+ T
      cells could be induced after combined immunization with recombinant influenza and
      vaccinia viruses. These findings may provide the basis for the development of new
      prophylactic and therapeutic strategies to prevent or control intracellular
      infections and certain malignancies.

PMID- 8871606
TI  - Rapid modulation of T lymphocyte surface antigens induced by Fas (CD95, APO-1)
      ligation.
AB  - Crosslinking the Fas (CD95, APO-1) antigen by mAb or Fas-ligand (Fas-L)
      expressing cells triggers apoptosis. We have investigated the early consequences
      of Fas signaling on the expression of various cell surface antigens on T
      lymphocytes. Incubation of Fas-sensitive Jurkat (JM) cells with agonistic anti
      Fas mAb induced rapid (within 4 hr) downmodulation of L-selectin (CD62L) and CD7
      but not of CD3 or CD71. No modulation was observed on Fas-expressing but Fas
      resistant JM variant 432.1. On PHA-activated, Fas-sensitive T cell blasts, anti
      Fas mAb rapidly triggered downmodulation of a variety of antigens, including CD2,
      CD4, CD8, CD7, CD44, LFA1alpha, LFA1beta, and CD62L, but not CD3, CD25, or CD26.
      Most of these antigens were not downmodulated by either CD3 crosslinking (except
      CD3) or PMA treatment (except CD3, CD4, and CD62L). Comparable patterns of
      biphasic CD44, LFA1alpha, and LFA1beta expression were observed on CD4+ and CD8+
      T cell blasts in response to Fas crosslinking. In these instances, downregulation
      occurred preferentially on cells undergoing rapid shrinkage. These results
      indicate that rapid downregulation of selected surface antigens is an early
      response of both normal and transformed T cells to Fas crosslinking.

PMID- 8871607
TI  - Interleukin-3 increases the incidence of 5-azacytidine-induced thymic lymphomas
      in pBOR-Il-3 mice.
AB  - Interleukin-3 (Il-3) is a glycoprotein produced by a CD4+CD8- subpopulation of T
      lymphocytes. Il-3 has been associated with the proliferation of bone marrow stem
      cells and their differentiation to granulocytes, macrophages, basophil/mast
      cells, megakaryocytes, erythroid cells, and neutrophils. The pBOR-Il-3 transgenic
      mice were developed by pronuclear microinjection to study how chemical insults
      modulate transcription of the Il-3 gene driven by a long-terminal repeat (LTR) of
      an endogenous retrovirus and to determine the biological consequences of
      interleukin-3 expression. We injected 5-azacytidine, a demethylating agent, to
      increase the LTR-driven expression of Il-3. Upon 5-azacytidine treatment, both
      the pBOR-Il-3 and the FVB/N nontransgenic controls developed thymic lymphomas.
      The pBOR-Il-3 mice developed thymic lymphomas at a higher frequency than the
      FVB/N mice. The thymic lymphoma cells were of a T-cell origin, as determined by T
      cell receptor gene rearrangement analysis, and, in most cases, were of monoclonal
      origin. According to flow cytometric analysis of CD3, CD4, and CD8 cell surface
      markers, the thymic lymphoma cells did not lose their ability to differentiate,
      but the differentiation process was aberrant. Flow cytometric analyses also
      revealed that in pBOR-Il-3 mice the thymic lymphomas are mostly of a CD8+CD4-
      origin, whereas in the FVB/N group, the predominant type of thymic lymphoma is of
      a CD4+CD8- origin.

PMID- 8871608
TI  - The suppression of T cell function and NF(kappa)B expression by serine protease
      inhibitors is blocked by N-acetylcysteine.
AB  - Direct evidence that N-acetylcysteine (NAC) enhances the immune response of
      peripheral blood T cells at the level of NF(kappa)B is presented. In addition,
      NAC blocks the suppression of T cell mitogenesis and cytokine production by
      protease inhibitors such as N-tosylphenylalanine chloromethyl ketone (TPCK). The
      proliferative responses of purified CD4+ or CD8+ T cells are suppressed more
      strongly by TPCK when anti-CD28 rather than the phorbol ester PMA is used as the
      mitogenic coactivator. Cytokine (IL-2, IL-6, INF-gamma) production is inhibited
      95-100% by concentrations of TPCK that totally suppress the mitogenesis of CD4+
      or CD8+ cells. Using electrophoretic mobility shift assays, we find that TPCK
      virtually abolishes (to less than 1%) the levels of NF(kappa)B (but not Oct-1)
      found in nuclear and whole cell extracts of activated T cells. Strikingly, the
      immunosuppressive effects of TPCK are blocked when T cells are pretreated for 15
      min with 5 mM NAC. NAC not only blocks the effect of TPCK but enhances
      mitogenesis and cytokine production (>2.5-fold in some cases) upon activation of
      unsuppressed T cells. Our data support the notion that NF(kappa)B and I(kappa)B
      proteases play obligate roles in T cell activation and mitogenesis, roles that
      are enhanced significantly by NAC.

PMID- 8871609
TI  - Coexpression of GD3 ganglioside with CD45RO in resting and activated human T
      lymphocytes.
AB  - The ganglioside GD3 is preferentially expressed on the surface of malignant T
      cell lymphoblasts and on resting T cells which express the memory cell phenotype,
      CD45RA-CD29+. However, GD3 expression in activated T cells and its potential
      function in proliferating normal and malignant T cells are unclear. Utilizing
      three-color immunostaining and flow cytometry, we examined changes in the
      expression of GD3 in conjunction with the RA and RO isoforms of CD45 during in
      vitro T cell activation. GD3 was equally expressed in resting CD4 and CD8 cells
      and was specifically found in the CD45RO+RA population. Activation of T cells
      with PHA resulted in an increased percentage of GD3+ cells. This increase was
      evident by the first day and was observed in the CD45RO (naive cell) population;
      by 2 days, GD3 was expressed heterogeneously in a large population of CD45RO+RA+
      cells. Further activation of T cells with PHA or anti-CD3 monoclonal antibody
      (OKT3) resulted in a further increase in GD3-expressing cells, and the increase
      in GD3 density correlated with increased CD45RO and loss of CD45RA. In contrast,
      increases in GD3 and interleukin-2 receptor (CD25) expression in response to PHA
      or OKT3 occurred independently, indicating that the GD3/ CD45RO coexpression
      observed was not a general consequence of cell activation. The results provide
      evidence for specific comodulation of GD3 and CD45RO during T cell mitogenesis,
      and thus suggest that these molecules may colocalize on the T cell surface.

PMID- 8871610
TI  - Up-regulation of Bcl-xL expression protects CD40-activated human B cells from Fas
      mediated apoptosis.
AB  - CD40--CD40L interactions between resting B cells and activated T cells are
      essential for germinal center formation. It has been shown that CD40L can induce
      both Fas expression and susceptibility to Fas-mediated killing in B cells, while
      anti-Ig can partially rescue B cells from Fas-mediated killing. However, the
      intracellular mechanism for this phenomenon is not known. We examined the
      expression of Fas and bcl-2 family gene products, such as Bcl-2, Bcl-x, Bax, and
      Mcl-1, in human tonsillar B cells. The activation of naive B cells by CD40L
      induced transient expression of Bcl-xL. As the Bcl-xL level decreased in CD40
      activated B cells, the cells became susceptible to apoptosis by anti-Fas
      antibodies. Though anti-Ig did not change the Fas expression, it protected CD40
      activated B cells from Fas-mediated killing by up-regulating Bcl-xL expression.
      The addition of anti-Ig did not significantly change Bcl-2, Bax, and Mcl-1 levels
      compared to those of B cells activated by CD40L alone.

PMID- 8871611
TI  - Level of myelopoiesis in the bone marrow is influenced by intestinal flora.
AB  - Mice were orally given kanamycin (50 mg/day/ mouse) for 1 or 2 weeks. Almost all
      bacteria in the intestine were eliminated within a week. In parallel with this
      elimination, the level of granulocytes in the bone marrow decreased from 41 to
      31%. Since the total number of bone marrow cells decreased as well (up to one
      third), the decrease in the level of granulocyte generation in the bone marrow
      was substantial. Kanamycin is not absorbed from the intestine into the body;
      namely, it does not have a direct effect on the bone marrow. It is speculated
      that the interaction of granulocytes or epithelial cells with intestinal bacteria
      accelerates the production of free radicals and superoxids, some cytokines, or
      unknown factors and that such substances then stimulate the generation of
      granulocytes in the bone marrow. The present results suggest that intestinal
      flora and other resident bacteria are important for maintaining the level of
      myelopoiesis in the bone marrow.

PMID- 8871612
TI  - The proteolytic environment involved in MHC class II-restricted antigen
      presentation can be modulated by the p41 form of invariant chain.
AB  - During biosynthesis, MHC class II associates with invariant chain which exists in
      two forms, p31 and p41. Both forms of invariant chain prevent peptide binding to
      class II, facilitate transport, and enhance class II localization to Ag
      processing compartments. In spite of these shared functions, presentation of some
      Ags can be selectively enhanced by expression of p41. Here we show that p41 can
      function as a protease inhibitor: 1) the functional and biochemical consequences
      of p41 expression can be mimicked by inhibiting cysteine proteases in vivo; 2)
      the amount of intracellular active cysteine proteases is dramatically decreased
      in p41-positive cells; and 3) a polypeptide corresponding to the p41-unique
      region is a potent inhibitor of cathepsin L in vitro. These data suggest that p41
      can enhance Ag presentation by reducing the proteolytic activity of the Ag
      processing compartment, thus protecting a subset of antigenic epitopes from
      excessive degradation.

PMID- 8871613
TI  - Mucosal IFN-gamma gene transfer inhibits pulmonary allergic responses in mice.
AB  - Th2 cytokines are associated with the airway inflammation and hyperreactivity in
      allergic asthma and are potential targets for developing novel therapies. The
      efficacy of a mucosal cytokine-gene transfer approach was examined in a mouse
      model for allergic asthma. We showed first that mucosal IFN-gamma gene transfer
      results in a significant expression of IFN-gamma in the pulmonary epithelium.
      Significantly, this approach inhibits both Ag- and Th2-cell-induced pulmonary
      eosinophilia and airway hyperreactivity. These findings suggest that mucosal IFN
      gamma gene transfer is effective in modulating pulmonary allergic responses and
      provides a basis for developing a novel therapeutic approach.

PMID- 8871614
TI  - Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice.
AB  - IL-13 shares many biologic responses with IL-4. In contrast to well-characterized
      IL-4 signaling pathways, which utilize STAT6 and 4PS/IRS2, IL-13 signaling
      pathways are poorly understood. Recent studies performed with STAT6-deficient
      mice have demonstrated that STAT6 plays an essential role in IL-4 signaling. In
      this study, the functions of peritoneal macrophages of STAT6-deficient mice in
      response to IL-13 were analyzed. In STAT6-deficient mice, neither morphologic
      changes nor augmentation of MHC class II expression in response to IL-13 was
      observed. In addition, IL-13 did not decrease the nitric oxide production by
      activated macrophages. Taken together, these results suggest that the macrophage
      functions in response to IL-13 were impaired in STAT6-deficient mice, indicating
      that IL-13 and IL-4 share the signaling pathway via STAT6.

PMID- 8871615
TI  - IFN-gamma plays a critical down-regulatory role in the induction and effector
      phase of myelin oligodendrocyte glycoprotein-induced autoimmune
      encephalomyelitis.
AB  - 129/Sv mice are resistant to induction of experimental autoimmune
      encephalomyelitis (EAE) induced with myelin oligodendrocyte glycoprotein peptide
      (MOG35-55). Mice of this strain lacking the gene coding for the ligand-binding
      chain of the IFN-gamma receptor develop EAE with high morbidity and mortality.
      Spleen cells from sensitized IFN-gammaR-/- mice proliferated extensively when
      stimulated with MOG peptide in culture and produced high levels of IFN-gamma and
      TNF but no detectable IL-4. Transfer of spleen cells from sensitized IFN-gammaR-/
      mice produced EAE in both IFN-gammaR+/+ and IFN-gammaR-/- recipients. Disease
      was severe in IFN-gammaR-/- recipients and mortality high (77%). Surviving mice
      remained moribund until termination of the experiments. IFN-gammaR+/+ recipients
      developed disease of equal severity, but with no mortality, and recovered
      significantly. These results indicate that IFN-gamma is not essential for the
      generation or function of anti-MOG35-55 effector cells but does play an important
      role in down-regulating EAE at both the effector and induction phase of disease.

PMID- 8871616
TI  - CD30 expression on human CD8+ T cells isolated from peripheral blood lymphocytes
      of normal donors.
AB  - By direct or indirect immunofluorescence using FITC as a fluorochrome, 0 to 2% of
      the T cells isolated from peripheral blood of normal healthy individuals was
      found to be CD30+. Using indirect immunofluorescence and phycoerythrin-labeled
      Ab, higher percentages of CD30+ T cells (3-31%) were repeatedly found in the
      peripheral blood of normal healthy donors. The majority (85-90%) of CD30+ T cells
      obtained from PBLs of normal healthy donors were found in the CD8+ cell
      population. Following FACS sorting of the T cell populations into CD30+ and CD30-
      subpopulations, approximately 85 to 90% CD30+ T cells were CD8+, whereas the CD30
      T cells were CD4+. Upon activation, the sorted CD30+ T cells produced both IFN
      gamma and IL-4. In contrast to previous reports, these results demonstrate that
      CD30+CD8+ T cells are present in significant numbers in the PBLs of normal
      healthy individuals.

PMID- 8871617
TI  - IL-12-induced activation of NK and T cells occurs in the absence of immediate
      early activation gene expression.
AB  - The responses of lymphocytes to IL-2 and IL-12, involving proliferation,
      differentiation, and cytokine production, are only partially overlapping, and may
      depend on induced differential expression of specific sets of genes. Using
      reverse-transcription PCR differential display, we isolated an mRNA species
      expressed in IL-2- but not IL-12-stimulated NK cells. This was identified as the
      mRNA encoding the transcription factor egr-1, which is expressed with fast
      kinetics in T and NK cells upon IL-2, but not IL-12, stimulation. Analysis of the
      accumulation of mRNA-encoding members of the AP-1 transcription factor family
      demonstrated that c-fos and junB are also expressed upon stimulation of NK and T
      cells with IL-2, but not IL-12, whereas expression of c-jun and junD is not
      modified by either cytokine. Accordingly, increased AP-1 DNA-binding activity and
      AP-1-dependent transcriptional activity were detected exclusively in IL-2
      stimulated cells. Analysis of the expression of genes reported to regulate
      cytokine-induced proliferation demonstrated that both IL-2 and IL-12 induce c-myc
      mRNA accumulation in NK and T cells, whereas only IL-2 induces bcl-2 expression.
      Our data provide the first demonstration that IL-12-mediated activation of T and
      NK cells does not involve expression of members of the immediate-early activation
      genes family (egr-1, c-fos, and junB), AP-1 transcriptional activity, or bcl-2
      expression. This indicates that functional differences observed in IL-2- and IL
      12-stimulated cells may depend, at least in part, on differential gene
      regulation.

PMID- 8871618
TI  - Flanking residues alter antigenicity and immunogenicity of multi-unit CTL
      epitopes.
AB  - CD8+ CTL responses constitute a critical component for vaccines developed to
      eliminate intracellular pathogens. One approach to achieve broad CTL diversity is
      based on genetically linking immunogenic peptides from multiple proteins to form
      poly-epitope Ags. To address the influence of flanking residues on class I Ag
      presentation, H-2d-restricted HIV-1 and mouse hepatitis virus CTL epitopes were
      linked via various spacer residues. The resulting 20 to 31 amino acid peptides
      were expressed using recombinant vaccinia viruses to monitor both CTL recognition
      and induction. Our data indicate that recognition is profoundly influenced by the
      nature of intervening residues forming carboxyl-terminal flanks for one and amino
      terminal flanks for the other epitope. Flanking amino acids with aromatic
      (tyrosine), basic (lysine), and small aliphatic side chains (alanine) supported
      efficient CTL recognition of both epitopes. By contrast, acidic and helix
      breaking residues (glycine, proline) specifically inhibited recognition of the
      adjacent amino-terminal epitope. Flanking residues inhibitory for recognition
      were also detrimental for CTL induction, suggesting similar processing mechanisms
      in vitro and in vivo. The ratios of peptide-specific CTL precursors primed by the
      tandem epitopes varied up to 50-fold depending on molecular context. These data
      demonstrate a substantial role of carboxyl-flanking residues in governing the
      efficiency of class I Ag presentation both in vitro and in vivo. The dramatic
      influence of flanking residues on the hierarchy of CTL responses indicates that
      CTL induction by poly-epitope Ags can be optimized by strategically linking
      epitopes via selection of appropriate spacer residues.

PMID- 8871619
TI  - Infusion of anti-B7.1 (CD80) and anti-B7.2 (CD86) monoclonal antibodies inhibits
      murine graft-versus-host disease lethality in part via direct effects on CD4+ and
      CD8+ T cells.
AB  - Efficient T cell proliferation requires costimulation via CD28/B7 or other
      pathways. Graft-vs-host disease (GVHD) is caused by activated donor T cells. We
      have found that the infusion of anti-B7.1 (CD80) + anti-B7.2 (CD86) mAb is
      effective in eliminating GVHD lethality induced by either CD8+ or CD4+ T cells.
      Donor CD4+ and CD8+ T cell expansion was inhibited by almost 100-fold as measured
      by enumerating thoracic duct lymphocytes (TDL) obtained early post-transplant.
      TDL retained anti-host responsiveness indicating that not all T cells were
      anergic. Although anti-CD80 or anti-CD86 mAb individually were ineffective in
      preventing CD8+ T cell GVHD lethality, each mAb was partially effective in CD4+ T
      cell-mediated GVHD. Because CD80 expression was found to be up-regulated on donor
      CD4+ TDL post-transplant, the GVHD capacity of donor CD4+ T cells deficient in
      CD80 was tested and found to be reduced similarly to that seen with anti-CD80
      mAb. These studies demonstrate that anti-CD80 + anti-CD86 mAb infusion is
      effective in preventing GVHD lethality by inhibiting donor CD4+ or CD8+ T cell
      expansion and provide the first evidence that CD80 expression on donor T cells is
      critical for optimal GVHD lethality.

PMID- 8871620
TI  - Soluble protein but not peptide administration diverts the immune response of a
      clonal CD4+ T cell population to the T helper 2 cell pathway.
AB  - BALB/c mice immunized with protein Ags such as OVA in adjuvant mount a Th1-type
      response. Inhibition of Th1 and development of Th2 cells can be induced by
      pretreating BALB/c mice with soluble OVA before priming. To investigate some
      aspects of this immune deviation in vivo, naive TCR transgenic T cells specific
      for the chicken OVA peptide 323-339 presented by I-A(d) molecules were adoptively
      transferred into normal BALB/c mice. The frequency and fate of the transferred T
      cells can be followed with an anti-clonotypic Ab. In response to priming with OVA
      in CFA, the transferred transgenic T cells expand and differentiate into Th1
      cells producing IL-2 and IFN-gamma. If recipient mice are injected with soluble
      OVA before priming, the frequency of transgenic T cells is not affected, but
      their expansion in response to Ag priming is inhibited. Yet, the fewer transgenic
      T cells recovered are not anergic, they proliferate as control cells when
      restimulated in vitro by plate-bound anticlonotypic Ab or by Ag. Analysis of Th
      phenotype indicates that pretreatment with soluble OVA has suppressed Th1 cell
      differentiation in favor of the generation of Th2 cells producing IL-4 and IL-5.
      Pretreatment with soluble peptide 323-339 also inhibits Th1 cell development, but
      fails to induce Th2 cell differentiation. Thus, pretreatment with soluble protein
      Ag or with synthetic peptide inhibits Th1 cell development, but only protein, not
      peptide, administration can deviate the in vivo response of a clonal T cell
      population from the Th1 to the Th2 pathway.

PMID- 8871621
TI  - Subcellular localization of CD80 receptors is dependent on an intact cytoplasmic
      tail and is required for CD28-dependent T cell costimulation.
AB  - CD28 provides a major costimulatory signal to T cells when it is cross-linked
      with mAb, immobilized recombinant ligand (CD80Ig or CD86Ig), or ligand-bearing
      cells but not when it is bound by specific Fab fragments or monomeric ligand. We
      wanted to determine how monomeric CD80 could cross-link CD28 since CD80 is
      expressed as a monomer on the surface of APC. We found that CD80 may interact
      with the actin-based cytoskeleton. To test whether the interaction of CD80 with
      the cytochalasin B-sensitive cytoskeleton was necessary for T cell costimulation
      through CD28, we constructed a tailless form of CD80 and generated stable
      transfectants of Chinese hamster ovary epithelial cells and Reh B cells
      expressing either the tailless or wild-type CD80 molecules. Unlike control cells
      expressing wild-type CD80, the tailless CD80 transfectants expressing equivalent
      levels of surface CD80 were not able to provide a costimulatory signal for anti
      CD3-induced T cell proliferation, up-regulation of CD25 (IL-2Ralpha) expression,
      or the induction of IL-2 secretion. Thus, the cytoplasmic tail of CD80 apparently
      is required to signal T cells. Confocal microscopic studies revealed that wild
      type CD80 and tailless CD80 have different patterns of subcellular distribution
      in both epithelial and lymphoid cells. Furthermore, T cell contact induces more
      patching and capping of CD80 in wild-type CD80-expressing cells than in tailless
      CD80-expressing cells. This suggests that the cytoplasmic region of CD80
      functions to localize CD80 in complexes required for effective T cell
      costimulation.

PMID- 8871622
TI  - Naive and effector CD4 T cells differ in their requirements for T cell receptor
      versus costimulatory signals.
AB  - We used naive CD4 cells and in vitro-derived Th1 and Th2 effectors from TCR
      transgenic mice to investigate the requirements of these subsets for TCR
      signaling and interactions with accessory molecules. Peptide Ag and immobilized
      anti-CD3 were used to provide different TCR signals. Anti-CD28 Ab or a panel of
      class II+ fibroblasts, expressing no accessory molecules or expressing
      intracellular adhesion molecule-1, B7-1, or both molecules, were used as APC or
      accessory cells (AC). An efficient naive T cell response required a strong TCR
      signal (high dose anti-CD3 or peptide) and high levels of multiple synergizing
      costimulatory signals, while effector cells responded efficiently to anti-CD3
      alone. Addition of AC only slightly augmented the effector response. Effectors
      responded to lower doses of peptide than naive cells. However, when peptide
      pulsed APC were used to stimulate effectors, requirements varied with the
      cytokine measured. The production of IL-4 did not require accessory molecules on
      APC. IL-2 production required interacting APC to express accessory molecules, but
      was little augmented by AC not presenting Ag, suggesting a requirement for
      noncostimulatory interactions. Proliferation of effectors closely paralleled IL-2
      production. Production of IFN-gamma was intermediate in dependence on accessory
      molecules, and production of IL-5 was nearly as dependent as IL-2. These results
      establish major differences between the induction of naive and effector responses
      and document differential requirements for the induction of distinct cytokines,
      indicating that different cytokines may be produced depending on the context of
      effector restimulation.

PMID- 8871623
TI  - Induction of activator protein (AP)-1 and nuclear factor-kappaB by CD28
      stimulation involves both phosphatidylinositol 3-kinase and acidic
      sphingomyelinase signals.
AB  - A major obstacle in understanding the signaling events that follow CD28 receptor
      ligation arises from the fact that CD28 acts as a costimulus to TCR engagement,
      making it difficult to assess the relative contribution of CD28 signals as
      distinct from those of the TCR. To overcome this problem, we have exploited the
      observation that activated human T cell blasts can be stimulated via the CD28
      surface molecule in the absence of antigenic challenge; thus, we have been able
      to observe the response of normal T cells to CD28 activation in isolation. Using
      this system, we observed that CD28 stimulation by B7-transfected CHO cells
      induced a proliferative response in T cells that was not accompanied by
      measurable IL-2 production. However, subsequent analysis of transcription factor
      generation revealed that B7 stimulation induced both activator protein-1 (AP-1)
      and nuclear factor-kappaB (NF-kappaB) complexes, but not NF-AT. In contrast,
      engagement of the TCR by class II MHC/superantigen, either with or without CD28
      ligation, resulted in the induction of NF-AT, AP-1, and NF-kappaB as well as IL-2
      production. Using selective inhibitors, we investigated the signaling pathways
      involved in the CD28-mediated induction of AP-1 and NF-kappaB. This revealed that
      NF-kappaB generation was sensitive to chloroquine, an inhibitor of acidic
      sphingomyelinase, but not to the phosphatidylinositol 3-kinase inhibitor,
      wortmannin. In contrast, AP-1 generation was inhibited by wortmannin and was also
      variably sensitive to chloroquine. These data suggest that in activated normal T
      cells, CD28-derived signals can stimulate proliferation at least in part via NF
      kappaB and AP-1 generation, and that this response uses both acidic
      sphingomyelinase and phosphatidylinositol 3-kinase-linked pathways.

PMID- 8871624
TI  - Enterotoxin septic shock protection and deficient T helper 2 cytokine production
      in growth hormone transgenic mice.
AB  - Neuroendocrine hormones have long been thought to play a role in lymphoid
      development and function. In particular, growth hormone has been shown to mediate
      thymic development as well as to promote T cell engraftment in severe combined
      immunodeficiency mice. Murine T helper cells are classified into two subsets
      based on their cytokine production pattern. Here, we report that transgenic mice
      for bovine growth hormone show significant alterations in T cell function and
      decreased capability for cytokine production, an effect that is more acute in T
      helper cells as measured by their inability to produce IL-4 upon in vivo
      injection with Staphylococcus aureus enterotoxin B. Furthermore, upon
      immunization with conventional Ags, growth hormone transgenic mice produce an
      altered Ig isotype pattern characterized by a response shift from IgG1 in
      nontransgenic mice to IgG2 in transgenic mice. The impaired T cell responses
      correlated with survival from septic shock mediated by bacterial enterotoxins. We
      conclude that growth hormone may have the potential of regulating immune
      responses in pathologic processes associated with hyperactivation of T cells or
      with massive cytokine production.

PMID- 8871625
TI  - Molecular analysis of the cytoplasmic domain of CD4: overlapping but
      noncompetitive requirement for lck association and down-regulation by Nef.
AB  - Expression of the HIV Nef protein results in the down-regulation of cell surface
      expression of CD4, with a di-leucine motif in the cytoplasmic domain of CD4 being
      required for this effect. However, our results indicate that this motif is not
      sufficient to confer sensitivity to down-regulation by Nef. Using site-directed
      mutagenesis and a transient expression system, we demonstrate that an alpha
      helical stretch of amino acids of the cytoplasmic tail of CD4 is also required
      for the down-regulation of CD4 induced by Nef. Some CD4 mutations allowed the
      discrimination between PMA- and Nef-induced down-regulation, suggesting the
      existence of multiple pathways. In addition, our results demonstrate that this
      motif is involved in the association of CD4 with the tyrosine kinase p56lck, thus
      defining a multifunctional domain of CD4. Although there is overlap between the
      sequence requirement for lck association and susceptibility to Nef, we fail to
      detect any preferential decrease in lck association with CD4 when Nef is
      expressed during acute HIV infection. Altogether, these results demonstrate that
      there is an overlapping, but noncompetitive, sequence requirement in the
      cytoplasmic domain of CD4 for lck association and down-regulation by Nef.

PMID- 8871626
TI  - Ultraviolet B radiation sensitizes a murine epidermal dendritic cell line (XS52)
      to undergo apoptosis upon antigen presentation to T cells.
AB  - Ultraviolet B irradiation of skin leads to immunologic tolerance, rather than
      immunity against newly introduced Ag, by altering the function of Langerhans
      cells, skin-specific members of the dendritic cell (DC) family. Using the murine
      epidermal-derived DC line, XS52, which retains important features of resident
      Langerhans cells, we have tested the hypothesis that UV radiation delivers a
      signal leading to apoptosis. XS52 cells, when exposed to modest fluences (25-100
      J/m2) of radiation, underwent apoptosis during a subsequent 6-h incubation with
      LPS or upon 6-h coculture with the keyhole limpet hemocyanin-specific Th1 clone
      HDK-1 in the presence of Ag. Specifically, XS52 cells treated in this way
      exhibited diminished cell viability, DNA laddering, and condensed staining of
      DNA. By contrast, none of these changes was induced by radiation alone, LPS
      alone, or coculture with T cells and Ag. Likewise, neither UV radiation plus T
      cells nor radiation plus Ag were sufficient to induce apoptosis, indicating that
      both T cells and Ag are required to induce apoptosis in the UV-sensitized cells.
      XS52 cells remained fully susceptible to T cell-mediated apoptosis even 16 h
      after irradiation, indicating the persistence of the sensitized state. These
      observations establish a model in which UV radiation induces a first event in
      which DC become sensitive to a second, apoptotic signal that is delivered by Ag
      specific interaction with T cells or by LPS. We suggest that DC undergoing
      apoptosis deliver unusual activation signals to T cells during Ag presentation,
      signals that lead to cellular unresponsiveness rather than to effective immunity.

PMID- 8871627
TI  - Isolation from human placenta of the IgG transporter, FcRn, and localization to
      the syncytiotrophoblast: implications for maternal-fetal antibody transport.
AB  - The IgG transporter responsible for ferrying maternal IgG across the human
      placenta to fetal circulation has not been identified, although the human
      homologue of the neonatal rat Fc receptor (FcRn), a heterodimer with pH-dependent
      IgG affinity, structurally similar to MHC Class I molecules, was recently
      proposed as a candidate. Affirming this hypothesis, we describe herein the
      specific copurification from human placenta of 46- and 14-kDa proteins by IgG
      affinity at acid pH. The larger protein, characterized by its amino acid sequence
      and by immunoblot, is the alpha-chain of human FcRn (hFcRn). The smaller is beta2
      microglobulin. Their coisolation by ligand affinity suggests that they comprise
      the hFcRn heterodimer. Placenta sections stained immunohistochemically with anti
      hFcRn alpha-chain peptide Abs show extensive expression of hFcRn in the
      syncytiotrophoblast and traces in the endothelium and other unidentified cells of
      the villus stroma. We find alpha-chain mRNA by Northern analysis in human
      placenta and in human trophoblast-like cell lines (JEG-3, ED27) but not in a
      human myelocytic cell line (HL60). We suggest that the placental hFcRn
      heterodimer may transport IgG to the fetus by a mechanism in which maternal IgG
      is pinocytosed nonspecifically and then carried to fetal tissues by a pH gradient
      from acidic endosomes to the pH-neutral basolateral surface of the
      syncytiotrophoblast. Furthermore, the known characteristics of FcRn suggest a
      wider function, that it is the receptor postulated by Brambell in the 1960s to
      regulate tissue and serum IgG concentrations by controlling IgG transport and
      catabolism.

PMID- 8871628
TI  - IL-10 inhibits lipopolysaccharide-induced murine B cell proliferation and cross
      linking of surface antigen receptors or ligation of CD40 restores the response.
AB  - The effects of IL-10 on murine B cell proliferation in vitro were investigated.
      IL-10 inhibited LPS-induced B cell proliferation with an EC50 of approximately
      500 pg/ml. IL-10-mediated inhibitory activity was not overtly associated with
      cytotoxicity or induction of apoptosis. The presence or the absence of T cells
      and mononuclear phagocytes did not affect the inhibitory activity of IL-10 on LPS
      induced proliferation. LPS-stimulated, IL-10-exposed B cells progressed from G0
      or from M to G1A of the cell cycle, but were inhibited from entry into subsequent
      phases. IL-10 had no discernible effect on B cell proliferation elicited with
      goat anti-mouse IgM plus IL-4. Moreover, cross-linking, but not mere ligation, of
      surface Ag receptors restored LPS-induced B cell proliferation in the presence of
      IL-10. The proliferative response to ligation of CD40 with anti-CD40 Abs was also
      not inhibited by IL-10, and as observed with goat anti-mouse IgM, the presence of
      such Abs in IL-10-containing B cell cultures allowed for the proliferative
      response to LPS. A variety of other Abs reactive with murine B cell surface
      markers were ineffective at modulating the response to IL-10. IL-1, IL-2, IL-4,
      IL-5, IL-6, IFN-gamma, and TGF-beta were also ineffective in this regard. These
      observations suggest that IL-10 has a role in the suppression of inappropriate B
      cell proliferation, i.e., proliferation by B cells that have not effectively
      interacted with relevant Ag or CD40 ligand.

PMID- 8871629
TI  - Defective B cell development in Snell dwarf (dw/dw) mice can be corrected by
      thyroxine treatment.
AB  - Snell dwarf (dw/dw) mice are deficient in anterior pituitary hormones due to a
      mutation in the gene encoding the Pit-1 transcription factor. Bone marrow B cell
      development is also suppressed in the mice, providing circumstantial evidence
      that one or more anterior pituitary-derived products, or factors induced by them,
      are required for normal B lymphopoiesis. However, concluding that this is the
      case is dependent on showing that hormonal treatment of dwarf mice reverses their
      B cell defects. dw/dw mice were treated with growth hormone (GH), insulin-like
      growth factor-I (IGF-I), or thyroxine in an attempt to restore bone marrow B
      lymphopoiesis. GH and IGF-I increased the number of B lineage cells in the bone
      marrow and spleen but did not restore the frequency of bone marrow pre-B cells to
      normal. However, bone marrow cellularity in thyroxine-treated dw/dw mice was
      comparable to that in control animals, and both the frequency and absolute number
      of B lineage cells had increased to normal or even above normal. Taken together,
      these data indicate that endocrine factors, especially those regulated by the
      hypothalamic-pituitary-thyroid axis, are potent B lymphopoietic factors.

PMID- 8871630
TI  - Cell surface ADP-ribosyltransferase regulates lymphocyte function-associated
      molecule-1 (LFA-1) function in T cells.
AB  - Post-translational modifications are important in regulating the functions of
      signal proteins. This is well established for intracellular proteins, but little
      is known in the case of extracellular domains of cell surface molecules. We
      recently described a cell surface protein, mono-ADP-ribosyltransferase (ADPRT),
      on cytotoxic T cells and showed that it mediates attachment of ADP-ribose to cell
      surface proteins. Concomitantly, cytolytic activity and cell proliferation are
      inhibited. Here we report that one of the principal proteins modified by this
      enzyme is lymphocyte function-associated molecule-1 (LFA-1). While both chains
      are ADP-ribosylated on the extracellular domain of the molecule, persistence of
      the modification differs between the chains. Label is released from the beta
      chain by 1 h, yet remains for at least 6 h on the alpha-chain. Loss of label is
      suppressed by phosphodiesterase inhibitors such as ADP-ribose and p
      nitrophenylthymidine 5'-monophosphate, pointing to the involvement of this class
      of enzyme. Modification of LFA-1 requires expression of the cell surface ADPRT
      and causes the loss of epitopes recognized by alpha- and beta-chain-specific Abs.
      Concomitantly, the generation of inositol phosphates induced by Ab cross-linking
      of LFA-1 is significantly inhibited. Consistent with this effect, anti-LFA-1
      induced homotypic cell adhesion is also inhibited. These effects are not seen in
      cells from which the ADPRT was removed by phospholipase C. Moreover, cells
      lacking the cell surface ADPRT are not inhibited by NAD in the cell adhesion
      assay, but gain this property upon transfection with the ADPRT gene. It is
      concluded that the cell surface protein mono-ADPRT regulates LFA-1 functions.

PMID- 8871631
TI  - Peptide sequence requirements for the recognition of HLA-B*2705 by specific
      natural killer cells.
AB  - NK clones that were inhibited by target cell expression of HLA-B*2705 displayed
      peptide-specific recognition of HLA-B*2705. To evaluate the specificity of this
      recognition, synthetic versions of 14 endogenous ligands of HLA-B*2705 were
      tested for their ability to provide protection from NK-mediated lysis by binding
      to surface HLA-B*2705 molecules on RMA-S cells deficient in the transporter for
      Ag presentation. Several unrelated peptides inhibited lysis by the same NK
      clones. Despite similar capacities to stabilize HLA-B*2705 molecules on RMA-S
      cells, the 14 peptides differed widely in their abilities to provide protection.
      Single amino acid substitutions in both a protective and a nonprotective peptide
      revealed the importance of residues 7 and 8 in the peptide for recognition by NK
      clones, thus localizing the peptide influence to a polymorphic region of the
      alpha-helix of HLA class I molecules known to control discrimination among
      allelic variants of HLA-B and HLA-C by NK cells.

PMID- 8871632
TI  - The xid mutation diminishes memory B cell generation but does not affect somatic
      hypermutation and selection.
AB  - In this study, we examine the relationship between primary and secondary T cell
      dependent immune responses using the response of xid mice to the hapten (4
      hydroxy-3-nitrophenyl)acetyl (NP) as an experimental model. The reduced serologic
      primary immune response of xid mice was demonstrated to be caused by a
      substantially decreased Ab-forming cell (AFC) generation. Furthermore, the
      germinal center reaction in the primary xid immune response was diminished and
      the frequency of NP-specific memory B cells prior to secondary immunization was
      reduced 10-fold. Despite the poor primary response of xid mice, secondary
      exposure to Ag generated a response that was qualitatively and quantitatively
      equal to that of wt mice. The number of IgG1 AFCs in spleen and bone marrow
      increased equally in both groups, as did the proportion of AFCs secreting high
      affinity Ab in both locations. The extent and distribution of somatic mutations
      in the V(H) genes of xid secondary response B cells was also found to be normal,
      indicating that the xid gene product is not critical for the processes that
      result in affinity maturation. Thus, although xid mice generate memory B cells of
      normal phenotype but at a substantially lower frequency, this does not limit the
      magnitude of the secondary response. Therefore, our results imply that the
      reduced memory B cell frequency in xid mice is still above some threshold value
      necessary for a normal secondary immune response.

PMID- 8871633
TI  - p126 (CDw101), a costimulatory molecule preferentially expressed on mucosal T
      lymphocytes.
AB  - Intestinal mucosal lymphocytes are defined by their anatomic location within the
      epithelium (intraepithelial lymphocytes), the interstitium between the epithelial
      basement membrane and the underlying muscularis mucosa (lamina propria
      lymphocytes), or in organized lymphoid tissues (Peyer's patches). Although
      intestinal intraepithelial lymphocytes have a distinct localization, their
      function has not been determined. To define cell surface proteins that are
      involved in intestinal intraepithelial lymphocyte localization or function,
      cultured human mucosal lymphocytes were used as immunogens to develop mAbs that
      react predominantly with this cell population in an immunohistochemical screening
      assay. Three mAbs were selected that subsequently were found by biochemical
      analysis to identify a 200-kDa homodimeric polypeptide on 88 to 98% of CD3+
      mucosal lymphocytes but only 18 +/- 13% of PBLs. Expression on granulocytes and
      monocytes was also observed. This polypeptide has been termed p126 based on its
      SDS-PAGE-determined M(r) under reducing conditions. Cleveland digest maps
      demonstrated similarity between the p126 and CDw101 polypeptides. Determined
      amino acid sequence analysis of the purified p126 polypeptide revealed that it is
      the protein product of the recently identified V7 gene, which has structural
      similarities to members of the Ig gene superfamily. Two of the anti-p126 mAbs
      were costimulatory with suboptimal concentrations of anti-CD3 mAb inducing
      proliferation of cultured intestinal intraepithelial lymphocytes. Thus, we
      conclude that p126 is CDw101 encoded by a gene that predicts a seven-Ig domain
      chain-like structure. It has restricted expression predominantly on mucosal T
      lymphocytes and appears to have a costimulatory function of special relevance for
      CD28- T cells and for mucosal lymphocytes.

PMID- 8871634
TI  - Herpes simplex virus blocks intracellular transport of HLA-G in placentally
      derived human cells.
AB  - Spontaneous fetal loss is associated with herpes simplex virus (HSV) infection as
      deduced from epidemiologic data. To date, the underlying mechanisms remain to be
      elucidated, but an immune component is suspected. HLA-G is a class I MHC molecule
      selectively expressed on extravillous cytotrophoblast; this cell type does not
      express conventional HLA-A or -B, whereas expression of novel HLA-C-like products
      has been reported. While its function remains unclear, a role for HLA-G in
      silencing NK cells that would otherwise attack cells devoid of classical class I
      molecules has been invoked. We here show that expression of HLA class I molecules
      is abrogated in HSV-infected choriocarcinoma cells, a phenomenon mediated by the
      virally encoded inhibitor of the transporter associated with Ag presentation,
      ICP47. These observations may provide a link between HSV infection and
      spontaneous fetal loss.

PMID- 8871635
TI  - Differential activation of the ERK, JNK, and p38 mitogen-activated protein
      kinases by CD40 and the B cell antigen receptor.
AB  - B cell antigen receptor (BCR)-induced apoptosis in the WEHI-231 B lymphoma cell
      line can be prevented by engaging CD40. We have used this cell line to
      investigate the role of mitogen-activated protein (MAP) kinases in integrating
      BCR and CD40 signaling. Each of the three types of MAP kinases, the extracellular
      signal-regulated kinases (ERKs), the c-Jun N-terminal kinases (JNKs), and p38,
      phosphorylates a distinct set of transcription factors. Thus, activating
      different combinations of MAP kinases could lead to distinct biological
      responses. We found that BCR engagement in WEHI-231 cells caused a 15- to 20-fold
      activation of ERK2 and a 2- to 3-fold stimulation of ERK1. CD40 did not activate
      either of these kinases, nor did it affect BCR-induced ERK activation. In
      contrast, CD40 engagement caused a 50- to 70-fold increase in JNK activity. BCR
      cross-linking caused a modest (4- to 8-fold) increase in JNK activity by itself
      and also potentiated CD40-induced JNK activation. Finally, CD40 caused strong
      activation of the p38 kinase as well as MAPKAP kinase-2, a downstream target of
      p38. BCR engagement caused only weak activation of the p38 pathway. In summary,
      the BCR strongly activates ERK2 and weakly activates ERK1, JNK, and p38, while
      CD40 markedly stimulates the JNK and p38 kinases. Thus, activation of only ERK2
      correlates with apoptosis in WEHI-231 cells, whereas full activation of all three
      MAP kinase pathways correlates with cell survival. The role of MAP kinases in
      regulating these responses remains to be tested.

PMID- 8871636
TI  - Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock
      cognate protein-like molecule and CD3+, CD4-, CD8-, TCR-alpha beta- killer T
      cells.
AB  - We previously reported that the 70-kDa heat shock cognate protein-like molecule
      (hsc70) is expressed on the cell surface along with the neoplastic transformation
      of rat fibroblast and that this molecule is recognized by CD3+, CD4-, CD8-, NKR
      P1-, and TCR-alphabeta- T (DNT) killer cells in an MHC class I-unrestricted
      fashion. We investigated the mechanism of interaction between hsc70 and DNT
      cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on
      the cell surface in almost the same density when the cells were growing in a
      conventional 5% FCS (5% W31) as when the cell growth was inhibited in the
      cultivation with 1% FCS (1% W31). However, DNT cells lysed only 5% W31, but not
      1% W31. Since these observations suggest that certain peptide Ags of the fast
      growing W31 cells may play a role in the interaction between hsc70 and DNT cells,
      we pulsed 1% W31 cells with trifluoroacetic acid (TFA)-extracted fast growing W31
      tumor Ags of less than 3000 Da in molecular size. We also pulsed 1% W31 with TFA
      extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data
      indicated that DNT cells were clearly cytotoxic to 1% W31 pulsed only with TFA
      extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this
      cytotoxicity. In addition, pronase K treatment of Ags clearly inhibited the
      cytotoxicity by DNT cells. Taken together, these data suggest that the complex of
      peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT
      cells.

PMID- 8871637
TI  - Changes in the cytoplasmic structure of CTLs during target cell recognition and
      killing.
AB  - CTL play a critical role in immune defense by recognizing and killing virally
      infected or tumor cells. In this report, the structure of cytoplasm within living
      CTL was monitored during CTL killing of target cells. Living CTL were
      simultaneously loaded with fluorescent 70,000- and 10,000-kDa dextran particles.
      The relative distribution of the large and small dextrans within CTL revealed
      subcellular heterogeneities in the submicroscopic structure of cytoplasm.
      Localized alterations in cytoplasmic structure correlated with specific events
      during CTL killing. Recognition of target cells was accompanied by a transient
      increase in large dextran accessibility over a broad front near the interface
      between CTL and target cells. This region narrowed to a smaller area from which
      pseudopodia were extended toward the target. During extension, there was a large
      difference between regions of high dextran accessibility within the pseudopod and
      more structured cytoplasm within the cell body. Areas undergoing structural
      changes showed localized foci of high dextran accessibility. During retraction,
      cytoplasmic structure became gradually more uniform throughout the protrusion and
      cell body. These observations revealed subcellular regions undergoing major
      changes during early stages of the killing response, and addressed the role of
      cytoplasmic solation in controlling CTL morphology. They support mechanisms of
      pseudopod extension driven by hydrostatic pressure and demonstrate a precise
      regulation of cortical structure to control the direction of pseudopod extension.

PMID- 8871638
TI  - Follicular dendritic cell-derived antigen and accessory activity in initiation of
      memory IgG responses in vitro.
AB  - Follicular dendritic cells (FDC) release Ag in developing germinal centers in the
      form of immune complex-coated bodies (iccosomes). Iccosomes are endocytosed by B
      cells, and the B cells process and present the FDC-derived Ag to T cells. By 3
      days after Ag challenge, Ab-forming cells producing IgG specific for the
      iccosomal Ag emerge from the developing germinal centers and home to the bone
      marrow, where most Ab in a secondary response are produced. In addition to
      providing Ag, FDC exhibit potent accessory activities that promote B cell
      proliferation. These observations prompted the hypothesis that both FDC-derived
      Ag and FDC-derived Ag-independent secondary signal(s) are essential for optimal
      secondary Ab responses. To test this hypothesis, methods were developed to
      separate Ag-bearing iccosomes from intact FDC, and we then examined the ability
      of isolated iccosomes to elicit secondary Ab responses in vitro in the presence
      and absence of intact FDC. In the absence of FDC, iccosomes bearing the
      appropriate Ag elicited only minimal levels of specific IgG. Proliferation
      studies revealed that iccosomes lacked the FDC accessory activity necessary to
      augment B cell proliferation. When a source of FDC lacking the relevant Ag but
      exhibiting accessory activity was added to the iccosomal/Ag/lymphocyte mixture,
      dramatic increases in IgG specific for the iccosomal Ag were obtained (increases
      were from low ng/ml to microg/ml levels of specific IgG). The results suggest the
      concept that Ag on FDC or on iccosomes signals B cells through B cell Ag
      receptor, the iccosome provides these B cells with Ag necessary to process and
      elicit T cell help, and a secondary signal(s) necessary to optimize the memory
      response is delivered to B cells by FDC in an Ag-nonspecific fashion.

PMID- 8871639
TI  - Defect of thymocyte emigration in a T cell deficiency strain (CTS) of the mouse.
AB  - As bone marrow progenitors migrate to the thymus, differentiate into
      immunologically competent T cells, then leave the thymus and home to the
      peripheral lymphoid organs, each migration or homing is an essentially critical
      process for T cell differentiation. Homing of thymocytes into peripheral lymphoid
      organs has been extensively analyzed. On the contrary, little is known about the
      mechanism whereby mature thymocytes emigrate from the thymus to peripheral
      lymphoid organs. In this work, we show that the mutant T cell deficiency strain
      (CTS) of mouse, previously described as a peripheral T cell deficiency strain,
      has a novel defect of mature thymocyte emigration process. Flow-cytometric
      analysis demonstrated a marked decrease in T lymphocytes in peripheral lymphoid
      organs and an accumulation of mature thymocytes in the thymus. Histologic study
      revealed the high concentration of thymocytes within the giant perivascular space
      at thymic corticomedullary junction. These accumulating cells closely resemble
      normal peripheral T lymphocytes in terms of cell surface phenotype and
      responsiveness to mitogens or allogeneic cells. They were found to express the
      Mel-14 Ag, the homing receptor to lymph nodes, and had a high capability of
      homing to peripheral lymphoid organs when explanted thymocytes were injected i.v.
      The intrathymic labeling methods detected hardly any emigrating CTS thymocytes
      from the thymus. These results indicate that emigration defect lies in the thymus
      of CTS mice, and suggest that this mutation is due to abnormal releasing
      mechanisms occurring between the thymus and the bloodstream. Complete delineation
      of the precise mechanisms of this defect, however, requires further studies.

PMID- 8871640
TI  - Induction of apoptosis by anti-CD3 epsilon F(ab')2 in antigen receptor transgenic
      murine T cells activated by specific peptide.
AB  - Peripheral T cell tolerance can be achieved through deletion of mature CD4+ cells
      activated by high dose Ag. We tested whether apoptosis of peripheral CD4+ cells
      could be induced by a stimulatory dose of Ag plus a soluble ligand to the
      nonpolymorphic epsilon-chain of the TCR-associated CD3 complex. CD4+ T cells from
      the DO10 mouse express a transgenic TCR-alphabeta specific for OVA peptide 323
      339 presented by I-A(d). OVA alone induced clonal activation and expansion of
      peripheral CD4+/TCR transgene+ cells. Simultaneous exposure to specific Ag plus
      soluble anti-CD3 Fos, a nonmitogenic anti-CD3epsilon genetically engineered
      F(ab')2-like Ab, blocked expansion and induced death of CD4+/TCR transgene+
      cells, but not CD4+/TCR transgene- T cells. In contrast, a mitogenic anti
      CD3epsilon Ab induced polyclonal activation and nonselective T cell death.
      Sequential stimulation by Ag followed by anti-CD3 Fos also induced death of TCR
      transgene+ cells, whereas stimulation by anti-CD3 Fos followed by Ag did not
      affect cell viability or function. Anti-CD3 Fos-induced death was associated with
      DNA fragmentation characteristic of apoptosis, was facilitated by IL-2, and was
      initiated by stimulation during the S-G2 phases of the cell cycle. Anti-CD3 Fos
      could induce deletion of Ag-activated T cells by apoptosis in vivo. Thus, a
      soluble, non-Fc-binding anti-CD3 Ab can induce programmed cell death of Ag
      activated peripheral CD4+ T cells by CD3epsilon cross-linking during S or G2.
      Peripheral T cell deletion by activation-driven apoptosis is under cell cycle
      control and can be exploited to achieve selective immunosuppression by
      nonmitogenic anti-CD3epsilon Abs.

PMID- 8871641
TI  - Analysis of a hot spot for DNA insertion suggests a mechanism for Ig switch
      recombination.
AB  - We recently reported that transfected DNA inserts into the VDJ-Cmu intron much
      more frequently than into average DNA, and that insertion within this intron
      occurs preferentially into the switch region. To gain information about the
      mechanisms involved in DNA insertion, we sequenced the 5' and 3' junctions of
      typical transformants. Although the junction sequences did not indicate a
      preferred insertion motif within the switch region, our results suggest that
      joining of the transfected and chromosomal DNAs is facilitated by short regions
      of identity. Our analysis of the insertions into the non-switch part of the
      intron suggests that breakage of the chromosomal DNA occurs preferentially at
      sites that are flanked by short complementary sequences. This correlation
      suggests that the self-complementary DNA might form short stem-loops, which, in
      turn, are prone to enzymatic cleavage and thus facilitate the insertion of
      transfected DNA. A model is proposed in which this effect can account for both
      the higher than average frequency of insertion into the VDJ-Cmu intron and the
      preference for the switch region within this intron. An extension of this model
      is proposed to explain why the repetitive switch regions are the preferred
      breakage/rejoining sites for isotype switch rearrangements.

PMID- 8871642
TI  - Kinetics of generation and persistence on membrane class II molecules of a viral
      peptide expressed on foreign and self proteins.
AB  - We had previously shown that a genetically engineered Ig expressing an
      immunodominant CD4+ T epitope corresponding to the 110-120 amino acids of
      influenza virus hemagglutinin (HA), activated T cells more efficiently than the
      synthetic peptide. Taking advantage of a T cell hybridoma specific for HA 110-120
      and transfected with a reporter gene under the IL-2 promoter, we studied the
      kinetics of generation and persistence on surface MHC-II of the HA 110-120
      peptide derived from various carriers. Our results show that the generation rate
      of immunogenic MHC II-peptide complex is dependent on the nature of the carrier.
      Abs specific for HA 110-120 peptide or for other epitopes on HA affect through
      various mechanisms the presentation of HA 110-120 peptide to T cells. The
      persistence of immunogenic MHC II-peptide complex on the surface of APC is not
      dependent on the nature of the carrier and correlates with the half-life of class
      II molecules, suggesting an irreversible binding of peptides to MHC-II molecules
      in 2PK3 murine B lymphoma cells.

PMID- 8871643
TI  - Residues critical for H-L disulfide bond formation in human IgA1 and IgA2.
AB  - There are two subclasses of human IgA, IgA1 and IgA2. IgA2 exists as two known
      allotypes, IgA2 m(1) and IgA2 m(2) with a recently reported novel IgA2 (IgA2(n))
      possibly representing a third allotype. The variants of human IgA differ in their
      H and L chain disulfide-bonding pattern; in IgA1, IgA2(n), and IgA2 m(2), a
      disulfide bond connects a cysteine residue in CH1 of the H chain with the L
      chains while human IgA2 m(1) has been reported to lack a covalent bond between
      the H and L chains. Here we have used site-directed mutagenesis to demonstrate
      that Cys133 is essential for the formation of the H-L disulfide bond in IgA1.
      However, IgA2 m(2) and the IgA2(n) but not IgA2 m(1) form an H-L disulfide in the
      absence of Cys133. IgA2 m(1) differs from IgA2 m(2) and the IgA2(n) at two
      positions in CH1; IgA2 m(1) has Pro212 and Pro221 whereas IgA2 m(2) and the
      IgA2(n) have Ser212 and Arg221. Our studies demonstrate that it is the presence
      of Pro221 in IgA2 m(1) that interferes with the H-L disulfide in the absence of
      Cys133. Contrary to what has been previously reported, protein purified from
      culture supernatants of IgA2 m(1) show some HL, H2L2, and H4L4J, suggesting that
      IgA2 m(1) can exist either as a form lacking H-L disulfide bonds or as a form
      with H-L disulfides.

PMID- 8871644
TI  - Multiple types of chimeric germ-line Ig heavy chain transcripts in human B cells:
      evidence for trans-splicing of human Ig RNA.
AB  - Germ-line transcripts from Ig heavy chain loci precede the occurrence of isotype
      switching and are thought to play an important though still controversial role in
      Ig class switching. In this study, we employed a reverse transcriptase-PCR
      approach to detect human chimeric Ig germ-line mRNA transcripts. Multiple types
      of chimeric Ig germ-line transcripts (Imu-Cepsilon, Iepsilon-Cmu, Imu-Cgamma4,
      Igamma-Cmu, Igamma-Cepsilon, Iepsilon-Cgamma, and Igamma4-Calpha1 transcripts)
      were readily detected in human B cells stimulated with IL-4 alone. Sequence
      analysis revealed that all of these chimeric Ig germ-line transcripts represented
      the I exons from one Ig locus spliced to the CH exons from another locus by using
      consensus sequences for splicing donor and acceptor sites, indicating that they
      were generated through splicing machinery. In the case of stimulation of human
      resting B cells with IL-4 alone, the chimeric Ig germ-line transcripts are likely
      derived from a trans-splicing mechanism, as the extensive searching did not find
      evidence that Ig class-switch recombination had occurred, which alternatively
      could give rise to chimeric Ig mRNA by mechanisms other than trans-splicing.
      Similarly, an EBV-transformed gamma2 rearranged B cell line, GM1500, which
      produces IgG2 and contains both gamma2 productive and epsilon germ-line
      transcripts, also expressed chimeric germ-line RNA (Iepsilon-Cgamma2) and epsilon
      productive transcripts (VDJ-Cepsilon). This line had no further sequential
      Sgamma2-Sepsilon rearrangements, providing evidence that the productive VDJ
      Cepsilon mRNA was derived from a transcriptionally active unrearranged epsilon
      gene locus by trans-splicing. Taken together, these results provide possible
      evidence that trans-splicing of germ-line Ig RNA transcripts occurs in human B
      cells.

PMID- 8871645
TI  - Molecular interactions between transfected human TCR, immunodominant myelin basic
      protein peptide 152-165, and HLA-DR13.
AB  - Chimeric TCR transfectants expressing human extracellular sequences and murine
      intracellular/transmembrane sequences were generated to analyze the trimolecular
      interaction between myelin basic protein (MBP) autoantigen, HLA, and a TCR
      isolated from a patient with multiple sclerosis. Chimeric transfectants responded
      to TCR activation by CD3- and TCRBV22S1-specific mAbs and by superantigen.
      Additionally, chimeric transfectants responded to autoantigen-specific activation
      with MBP 152-165 when presented by DR(alpha,beta1*1301) independent of the CD4
      adhesion molecule. Transfectants did not respond to Ag presented by other HLA-DR
      molecules, including the closely related DR(alpha,beta1*1302). In peptide-binding
      studies with a panel of serial alanine-substituted MBP peptides, HLA contact
      residues necessary for anchoring MBP 152-165 to DR(alpha,beta1*1301) were also
      defined: 154 (F), 159 (R), and 162 (R). The chimeric TCR transfectant's
      differential response to a similar panel of MBP analogues defined residues that
      interact with the TCR: 153 (I), 155 (K), 156 (L), 160 (D), and 161 (S). Analysis
      of molecular interactions, such as those described in this work, may be central
      to developing new strategies for suppressing Ag-specific responses in human
      autoimmune disease.

PMID- 8871646
TI  - Postinduction transcriptional repression of E-selectin and vascular cell adhesion
      molecule-1.
AB  - TNF-alpha induction of the E-selectin and vascular cell adhesion molecule-1 (VCAM
      1) genes leads to transient accumulation of high levels of mRNA in endothelial
      cells. The increase in these mRNAs after induction is due to an increase in the
      rate of gene transcription, which is maintained for several hours in the
      continuous presence of cytokine. Cytokine-induced transcriptional activation of
      these genes requires the transcription factor, nuclear factor-kappaB. Following
      removal of TNF-alpha, there is rapid postinduction transcriptional repression
      common to both of these genes. The repression is protein synthesis dependent and
      correlates with protein synthesis-dependent loss of both the p50 and p65 subunits
      of nuclear factor-kappaB from the nucleus. IkappaBalpha is capable of
      specifically displacing endothelial-derived heterodimeric p50/p65 from the E
      selectin and VCAM-1 kappaB elements, while having no effect on binding of p50
      homodimer. In the presence of agents that block proteasomal degradation of
      IkappaBalpha, endogenous IkappaBalpha can be visualized in the nucleus of both
      resting and TNF-alpha-activated endothelial cells. Endogenous IkappaBalpha is
      readily detected in the nucleus of HeLa cells, and its nuclear localization is
      increased following removal of TNF-alpha. Repression of E-selectin and VCAM-1
      transcription following cytokine removal requires the loss of nuclear p50 and
      p65, and involves IkappaBalpha. This postinduction transcription repression
      mechanism may be one component of a program that prevents inappropriate and
      prolonged expression of adhesion molecules.

PMID- 8871647
TI  - Specificity and degeneracy in peptide binding to HLA-B7-like class I molecules.
AB  - The HLA-B7-like binding supertype includes several different HLA-B molecules.
      Herein, the primary and secondary anchor specificities of the five most common
      HLA-B7-like molecules (B*0702, B*3501, B51, B*5301, and B*5401) were defined by
      the use of molecular binding assays, analogue peptides, and large sets of
      peptides corresponding to naturally occurring sequences. All five B7-like
      molecules analyzed preferentially bound 9-mers, with a stringent requirement for
      proline in position 2, while a variety of hydrophobic or aromatic residues were
      well tolerated at the C-terminal anchor position. Although most peptides bound in
      an allele-specific fashion, approximately 20% of the binders identified were
      degenerate and bound at least three of the five B7-like molecules analyzed with
      affinities of 500 nM or less. It was also noted that, in general, peptides that
      bind with high affinity to any given one B7-like molecule were also most
      frequently capable of degenerate binding. Prominent roles for secondary anchors
      in positions 1 and 3 were observed for most B7-like molecules, and secondary
      anchor motifs were utilized to derive an HLA-B7-like supermotif. The validity of
      this B7-like supermotif was tested by a blind prediction set. Finally, the B7
      like supermotif was utilized to derive a general strategy for rationally
      engineering peptide analogues of naturally occurring sequences with greatly
      increased binding affinity and degeneracy. Such engineered supermotif binding
      peptides may be of significant utility in the development of peptide-based
      vaccines against chronic viral diseases and cancer.

PMID- 8871648
TI  - HMG box-activating factors 1 and 2, two HMG box transcription factors that bind
      the human Ig heavy chain enhancer.
AB  - We present the isolation of two cDNAs that encode distinct, yet related, proteins
      that bind the HE2 region of the human Ig heavy chain (IgH) enhancer. Designated
      HMG box-activating factors (HAF) 1 and 2, the two proteins are new members of the
      HMG box family of DNA binding proteins. Both are potent transcription activators
      when expressed 1) as GAL4 fusions targeted to promoters containing GAL4
      operators, or 2) as intact proteins targeted to minimal promoters containing
      binding sites derived from the IgH enhancer. HAF-1 and HAF-2 mRNAs are apparently
      expressed in both B cells and non-B cells. However, activity generated by the
      isolated HE2 region in B cells is dependent on both an intact HAF-1/HAF-2 binding
      site and at least one additional site that has been reported previously to bind a
      B cell-restricted protein. Our results suggest a collaborative role for either or
      both HAF-1 and HAF-2 in establishing the B cell activity of the human IgH
      enhancer.

PMID- 8871649
TI  - A critical role of Sp1- and Ets-related transcription factors in maintaining CTL
      specific expression of the mouse perforin gene.
AB  - This study was designed to determine the potential cis-elements involved in
      transcriptional regulation of the mouse perforin gene. DNase I hypersensitive
      site (DHS) mapping revealed that the perforin locus contained six DHS within 7.0
      kb of the 5' upstream sequence (-7.0 kb) and two DHS in intron 2. The six 5'
      upstream and one intronic DHS were detected in only perforin-expressing
      lymphocytes. Chloramphenicol acetyltransferase (CAT) activities directed by 5'
      upstream promoter were detected preferentially in perforin-expressing cell lines.
      A construct termed PFP5a containing -795 bp exhibited the highest CAT activity,
      and PFP9a20 containing only -73 bp also produced significantly high CAT activity
      in CTLL-R8 cells. The proximal region in PFP9a20 contained two potential Sp1
      binding sites (GC box and GT box) and one Ets binding site (EBS). Electrophoretic
      mobility shift assay showed that each of the cis-elements bound specific protein
      factors. When single-point mutation was introduced to each GC box, EBS, and GT
      box in PFP9a20, at least 3-fold less CAT activity was observed in CTLL-R8 cells.
      To confirm the importance of the three cis-acting elements in the perforin gene
      expression, point mutation was introduced again to each proximal GC box, EBS, and
      GT box of PFP5a. The point mutations resulted in a 2.5- to 3-fold reduction of
      CAT activity. The results suggest that a combination of the three proximal cis
      acting elements may constitute a minimal region responsible for CTL-specific
      expression of perforin.

PMID- 8871650
TI  - Control of endogenous mouse mammary tumor virus superantigen expression in SJL
      lymphomas by a promoter within the env region.
AB  - SJL mouse lymphomas (reticulum cell sarcomas, or RCSs) of germinal center B cell
      origin express an endogenous mouse mammary tumor virus (mtv-29) superantigen
      (vSAg) that stimulates Vbeta16+ T cells to produce cytokines essential for RCS
      growth. Normal or LPS-activated SJL/J B cells contain two to three larger mRNAs
      for mouse mammary tumor virus-long terminal repeat (LTR) but not the 1.8-kb mRNA,
      which is prominent in RCS cells and encodes the vSAg-29. mRNAs from RCS and
      normal lymphoid cells were characterized by Northern hybridization using DNA
      probes from various regions of mtv-29, as well as by reverse transcription PCR,
      RNase protection, and primer extension. The larger mtv-29 transcripts, coding for
      envelope protein, are initiated in the 5' LTR, as expected. Surprisingly, the 1.8
      kb mRNA, encoding the open reading frame of the LTR, is initiated in the middle
      of the env region and spliced in the 3' env. This is the first report of an mtv
      vSAg transcript that is not controlled by promoter(s) located in the 5' LTR. The
      env initiation site appears identical to that of the mouse mammary tumor virus
      env transcriptional activator-directed PMA-induced defective LTR transcript in
      the C57BL6 T cell lymphoma, EL-4. The stimulus independence, B lymphoma
      specificity, and absence of deletions within either the 5' or 3' LTR regions of
      mtv-29 in RCS distinguish the situation in RCS cells from that in EL-4. These
      findings suggest that the novel mtv-29-vSAg transcript reflects an RCS-cell
      specific regulation of transcription.

PMID- 8871651
TI  - Control of parasitemia and survival during Trypanosoma brucei brucei infection is
      related to strain-dependent ability to produce IL-4.
AB  - We studied non-MHC gene-dependent expression of a number of cytokines in relation
      to host defense and survival during Trypanosoma brucei brucei (Tbb) infection in
      mice. In particular, the role of IL-4 was explored with use of genomically IL-4
      disrupted mice and in vivo Ab blocking. Splenocytes from MHC-identical B10.Q
      (relatively resistant) mice showed day 5 postinfection higher numbers of IL-4
      mRNA expressing cells than C3H.Q (highly susceptible). A trypanosome-derived
      lymphocyte triggering factor, which is released by Tbb to polyclonally activate
      CD8+ T cells, stimulated naive splenocytes in vitro to a higher IL-4 response in
      B10.Q than in C3H.Q mice. The C3H.Q mice developed an extremely high parasitemia,
      showed a low Ab response against the variant surface glycoprotein (VSG), and had
      a mean survival time of 42 days. Conversely, B10.Q mice had lower parasitemia,
      mounted higher anti-VSG response, and had a mean survival time of 56 days.
      Deletion of the IL-4 gene had no influence on the infection in C3H.Q mice, while
      in B10.Q mice the deletion was associated with lower anti-VSG Ab levels and
      higher parasitemia. Paradoxically, B10.Q mice with disrupted IL-4 gene survived
      longer than the wild type. Anti-IL-4 Ab-blocking experiments in vivo displayed an
      enhanced parasitemia and prolonged survival in infected B10.Q mice. We conclude
      that 1) a non-MHC gene-related and CD8+-dependent ability to produce IL-4 partly
      determines the susceptibility to Tbb infection; and 2) IL-4, although involved in
      controlling the levels of parasitemia by its effects on immunoglobulin synthesis,
      also can have toxic effects on the animals.

PMID- 8871652
TI  - Key epitopes on the ESAT-6 antigen recognized in mice during the recall of
      protective immunity to Mycobacterium tuberculosis.
AB  - The recall of long-lived immunity in a mouse model of tuberculosis (TB) is
      defined as an accelerated accumulation of reactive T cells in the target organs.
      We have recently identified Ag 85B and a 6-kilodalton early secretory antigenic
      target, designated ESAT-6, as key antigenic targets recognized by these cells. In
      the present study, preferential recognition of the ESAT-6 Ag during the recall of
      immunity was found to be shared by five of six genetically different strains of
      mice. Overlapping peptides spanning the sequence of ESAT-6 were used to map two T
      cell epitopes on this molecule. One epitope recognized in the context of H-2b,d
      was located in the N-terminal part of the molecule, whereas an epitope recognized
      in the context of H-2a,k covered amino acids 51 to 60. Shorter versions of the N
      terminal epitope allowed the precise definition of a 13-amino acid core sequence
      recognized in the context of H-2b. The peptide covering the N-terminal epitope
      was immunogenic, and a T cell response with the same fine specificity as that
      induced during TB infection was generated by immunization with the peptide in
      IFA. In the C57BL/6j strain, this single epitope was recognized by an exceedingly
      high frequency of splenic T cells (approximately 1:1000), representing 25 to 35%
      of the total culture filtrate-reactive T cells recruited to the site of infection
      during the first phase of the recall response. These findings emphasize the
      relevance of this Ag in the immune response to TB and suggest that immunologic
      recognition in the first phase of infection is a highly restricted event
      dominated by a limited number of T cell clones.

PMID- 8871653
TI  - Detection of Borrelia burgdorferi-specific CD8+ cytotoxic T cells in patients
      with Lyme arthritis.
AB  - T cells are believed to play an important role in the pathogenesis of Lyme
      arthritis (LA), an inflammatory joint disease caused by the spirochete Borrelia
      burgdorferi (Bb). The presence or absence of certain Bb-specific CD4+ T helper
      cells has been associated with prognosis. Since recent observations suggested the
      activation of CD8+ T cells during infection with Bb, we searched for CD8+
      cytotoxic T lymphocytes in patients with LA. CD8+ T cell lines were generated
      from peripheral blood and synovial fluid of five patients with LA. In addition,
      CD8+ T cells were expanded by Ag-specific stimulation in bulk cultures. A
      cytotoxicity assay was established using target cells infected with recombinant
      vaccinia viruses expressing the borrelial proteins outer surface protein (Osp) A,
      OspB, or flagellin. We found Bb-specific CTL lines derived from the peripheral
      blood of three patients with LA with specificity for flagellin, OspA, and OspB.
      All Bb-specific CTL lines were CD3+, CD8+, and TCRalphabeta, and cytotoxic
      activity was HLA class I restricted. Moreover, CD8+ T cells expanded by Ag
      specific stimulation in vitro demonstrated Bb-specific and HLA class I-restricted
      lysis toward individual borrelial proteins. Interestingly, Bb-specific lytic
      activity was only detected in patient samples obtained after the disappearance of
      arthritis. We report the detection of Bb-specific cytotoxic CD8+ T cells in
      patients with LA. The induction of specific CD8+ T cells may play an important
      role in disease control and may have important bearings for the development of
      effective vaccines against Lyme borreliosis.

PMID- 8871654
TI  - Persistent cytokine expression in trigeminal ganglion latently infected with
      herpes simplex virus type 1.
AB  - Following ocular infection, herpes simplex virus type 1 (HSV-1) establishes
      latency in trigeminal ganglion (TG) neurons. Using reverse transcription-PCR,
      cytokine gene expression was analyzed in the TGs of mice infected with HSV-1. IL
      2, TNF-alpha, IFN-gamma, IL-10, and RANTES mRNAs were readily detected in TGs
      taken from mice 7 days postinoculation (PI). Likewise, IL-2, IL-6, IL-10, and IFN
      gamma protein were detected by ELISA of TG homogenates. Between 5 and 45 days PI,
      IL-10, IFN-gamma, TNF-alpha, and RANTES mRNAs were detected in nearly 100% of
      latently infected TGs (latent infection was confirmed by reverse transcription
      PCR detection of HSV-1 latency-associated transcripts). T cell-associated
      cytokine and chemokine mRNAs (IL-2, IL-10, IFN-gamma, and RANTES) were still
      detected in the majority of latently infected TG samples taken between 60 and 135
      days PI. In contrast, these cytokine mRNA species were rarely detected in
      uninfected TGs. Measurement of serum Abs to HSV-1 at different times revealed
      that anti-HSV-1 Ab concentrations approached a plateau in mice by 30 days PI but
      remained at high levels 67 and 125 days PI. Although there was molecular evidence
      of an ongoing immune response to HSV-1 in latently infected TG, histologic
      analysis indicated that very few mononuclear cells remained in the ganglion 60
      days PI. Collectively, the results suggest that residual lymphocytes encounter
      viral Ag during HSV-1 latency with sufficient frequency to remain activated. The
      paradox of a persistent immune response against a latent infection is discussed.

PMID- 8871655
TI  - DNA vaccination primes MHC class I-restricted, simian virus 40 large tumor
      antigen-specific CTL in H-2d mice that reject syngeneic tumors.
AB  - We investigated the stimulation of a MHC class I-restricted response of CTL to
      the SV40 large tumor Ag (T-Ag) by different vaccination strategies in H-2d and H
      2b mice. Immunization with plasmid DNA or exogenous T-Ag, or infection with SV40,
      primed CTL to T-Ag in H-2b mice; these three different types of Ag delivery
      primed T-Ag-specific CTL populations with similar epitope/restriction
      specificities. In H-2d mice, i.m. immunization with plasmid DNA, but neither
      immunization with exogenous protein Ag nor SV40 infection, primed CTL to T-Ag. T
      Ag-specific H-2d CTL were primed by DNA-based immunization in vivo, expressed the
      CD4-CD8+ phenotype, and were L(d)-restricted. In H-2d (DBA/2) mice, T-Ag-specific
      immune responses primed by plasmid DNA injection, but not those primed by
      exogenous T-Ag or SV40 infection, mediated CD8+ CTL-dependent rejection of T-Ag
      expressing P815/T tumor grafts. The data indicate that immunization by plasmid
      DNA injection is an efficient strategy to induce class I-restricted CTL responses
      against oncogene-encoded Ags of low immunogenicity that mediate tumor rejection.

PMID- 8871656
TI  - Natural resistance to intracellular infections: Nramp1 encodes a membrane
      phosphoglycoprotein absent in macrophages from susceptible (Nramp1 D169) mouse
      strains.
AB  - The mouse Nramp1 gene (Bcg/Ity/Lsh) controls innate defense to infection with
      intracellular parasites such as Mycobacterium, Salmonella, and Leishmania.
      Sequence analysis of Nramp1 predicts a hydrophobic, membrane-associated protein
      expressed exclusively in monocyte/macrophage lineages. A single G169D
      substitution within the fourth predicted transmembrane domain of Nramp1 is
      associated with susceptibility to infection (Bcg) in inbred mouse strains. To
      initiate the biochemical characterization of the Nramp1 protein and to analyze
      the molecular basis of susceptibility associated with the Nramp1(D169) allele,
      oligopeptides derived from Nramp1 and two fusion proteins containing the first 54
      and the last 35 residues of Nramp1 were used to raise specific anti-Nramp1
      antisera. In addition, a c-Myc epitope (EQKLISEEDL) was introduced in-frame at
      the C terminus of Nramp1 to follow its expression in a yeast heterologous system.
      Western analysis of crude membrane fractions from yeast demonstrated that Nramp1
      is indeed an integral membrane protein (resistant to urea extraction). In
      resident Bcg(r) (129sv, Nramp1(G169)) macrophages, one of the anti-Nramp1
      antisera identified by immunoprecipitation a protein of 90,000 to 100,000
      apparent m.w. that was absent in macrophages from knockout mice bearing a null
      mutation at Nramp1. The Nramp1 protein could be metabolically labeled with
      orthophosphate and was sensitive to glycosylase treatment, verifying that Nramp1
      is an integral membrane phosphoglycoprotein. Parallel analysis of macrophage
      extracts from Bcg(s) mouse strains (C57BL6/J and BALB/c, Nramp1(D169)) failed to
      detect mature Nrampl protein in these cells, suggesting that the G169D mutation
      at Nramp1 prevents proper maturation or membrane integration of the protein,
      resulting in its rapid degradation.

PMID- 8871657
TI  - Expression of type II nitric oxide synthase in primary human astrocytes and
      microglia: role of IL-1beta and IL-1 receptor antagonist.
AB  - In this work, we studied the expression of type II nitric oxide synthase (NOS) in
      primary cultures of human astrocytes and microglia. Cytokine-activated human
      fetal astrocytes expressed a 4.5-kb type II NOS mRNA that was first evident at 8
      h, steadily increased through 48 h, and persisted through 72 h. The inducing
      signals for astrocyte NOS II mRNA expression were in the order IL-1beta + IFN
      gamma > IL-1beta + TNF-alpha > IL-1beta. SDS-PAGE analysis of cytokine-stimulated
      astrocyte cultures revealed an approximately 130-kDa single NOS II band that was
      expressed strongly at 48 and 72 h (72 h > 48 h). Specific NOS II immunoreactivity
      was detected in cytokine-treated astrocytes, both in the cytosol and in a
      discrete paranuclear region, which corresponded to Golgi-like membranes on
      immunoelectron microscopy. In human microglia, cytokines and LPS failed to induce
      NOS II expression, while the same stimuli readily induced TNF-alpha expression.
      In cytokine-treated human astrocytes, neither NOS II mRNA/protein expression nor
      nitrite production was inhibited by TGF-beta, IL-4, or IL-10. In contrast, IL-1
      receptor antagonist exerted near complete inhibition of NOS II mRNA and nitrite
      induction. Monocyte chemoattractant peptide-1 mRNA was induced in TGF-beta
      treated astrocytes, demonstrating the presence of receptors for TGF-beta in
      astrocytes. These results confirm that in humans, cytokines stimulate astrocytes,
      but not microglia, to express NOS II belonging to the high output nitric oxide
      system similar to that found in rodent macrophages. They also show that the
      regulation of type II NOS expression in human glia differs significantly from
      that in rodent glia. A crucial role for the IL-1 pathway in the regulation of
      human astrocyte NOS II is shown, suggesting a potential role for IL-1 as a
      regulator of astrocyte activation in vivo.

PMID- 8871658
TI  - Induction of nitric oxide synthase in mouse dendritic cells by IFN-gamma,
      endotoxin, and interaction with allogeneic T cells: nitric oxide production is
      associated with dendritic cell apoptosis.
AB  - Nitric oxide (NO) is an important effector molecule that is involved in immune
      regulation and host defense. In this study, highly purified NLDC 145+ (DEC-205+)
      MHC class II(bright) B7-2+ dendritic cells (DC) propagated from normal mouse bone
      marrow in response to granulocyte-macrophage CSF + IL-4 were induced to produce
      NO by IFN-gamma and LPS. NO production was inhibited by the nitric oxide synthase
      (NOS) inhibitor N(G)-monomethyl-L-arginine (NMMA). Nitrite also accumulated in
      mixed leukocyte culture supernatants as the result of coculture of DC with
      purified naive allogeneic T cells. Furthermore, NO production was induced by CD40
      ligation. Suboptimal T cell proliferation observed at high relative
      concentrations of DC correlated with increased NO production and was mitigated by
      NMMA. Induction of mRNA for an inducible NOS (iNOS) in DC was confirmed by
      Northern blotting, whereas intracellular iNOS was visualized by two-color flow
      cytometry and by both immunofluorescent and immunogold labeling in a
      subpopulation of IFN-gamma + LPS-stimulated cells. Both endogenous NO production
      and exposure of unstimulated DC to the NO donor S-nitroso-N-acetyl-penicillamine
      (SNAP) resulted in DC apoptosis. Thus, although DC function initially as the most
      potent APCs for T cell activation, DC induced to synthesize NOS by IFN-gamma may
      inhibit (allogeneic) T cell proliferation: NO may suppress lymphocyte
      proliferation and also induce apoptosis of the most potent source of
      alloantigenic stimulation.

PMID- 8871659
TI  - Transcriptional up-regulation of intracellular adhesion molecule-1 in human
      endothelial cells by the antioxidant pyrrolidine dithiocarbamate involves the
      activation of activating protein-1.
AB  - The redox status of the cell plays an essential role in regulating signal
      transduction, transcription factor activity, and expression of cell surface
      molecules. In this study, we show that pyrrolidine dithiocarbamate (PDTC), a
      potent antioxidant agent, upregulated the cell surface expression of
      intercellular adhesion molecule-1 (ICAM-1) in human endothelial cells (EC).
      Further analysis of PDTC-mediated ICAM-1 up-regulation revealed that PDTC
      increased ICAM-1 mRNA levels and augmented its gene promoter activity.
      Transfection experiments in EC with reporter constructs harboring nested deletion
      fragments of the ICAM-1 promoter indicated the presence of a functional PDTC
      responsive region located between positions -136 to -353 of the promoter. Gel
      retardation assays together with supershift analysis revealed that PDTC induced
      the binding of c-fos and c-jun to a consensus activating protein-1 (AP-1) binding
      site located at position -284. PDTC alone or in combination with TNF-alpha
      enhanced AP-1-dependent transactivation in HUVEC, as determined by DNA binding
      assays. The functional implication of AP-1 in the transcription of the ICAM-1
      gene was further demonstrated by cotransfection experiments in which a c-jun
      expression vector induced the promoter activity of the PDTC-responsive element of
      the ICAM-1 promoter. Taken together, these results indicate that the antioxidant
      PDTC induces transcriptional activation of ICAM-1 and that this induction is
      mediated at least in part by the transcription factor AP-1. This mechanism might
      be operative in pathologic conditions in which a redox imbalance plays a key
      role, such as ischemia/reperfusion injury or arteriosclerosis.

PMID- 8871660
TI  - Synthesis of the CC-chemokines MIP-1alpha, MIP-1beta, and RANTES is associated
      with a type 1 immune response.
AB  - Lymphocytes regulate the immune response by secreting cytokines that control the
      activity and function of effector cells. Chemokine subsets are ideal candidates
      for recruitment of specific effector cells to inflammatory sites or to other
      lesions because of their selective chemoattractant activities. Given the Th1-Th2
      model of immune regulation and the particular role of leukocyte recruitment for
      the outcome of the response, we analyzed whether a subset of human chemokines is
      associated with a specific type of immune response. Therefore, we have analyzed
      the human T cell response to Ags prepared from Yersinia enterocolitica and
      Ascaris suum with respect to cytokine mRNA-synthesis and secretion. For the Gram
      negative bacterium Y. enterocolitica, induction of a type 1 response is indicated
      by IL-2 and IFN-gamma production, and for the nematode A. suum, a type 2 response
      is based on IL-4 and IL-5 production. Interestingly, expression of three CC
      chemokines (i.e., MIP-1alpha, MIP-1beta, and RANTES) correlated with the type 1
      response induced by Y. enterocolitica Ag. Chemokine secretion is not restricted
      to T lymphocytes; therefore, synthesis of MIP-1alpha, MIP-1beta, and RANTES was
      also characterized in human T cell clones that display a cytokine pattern
      indicative of the Th2, Th0, or Th1 phenotype. Again CC-chemokine secretion
      correlated with the Th1-like phenotype. In six analyzed IL-2- and IFN-gamma-
      secreting Th1 clones and in two Th0 clones, MIP-1alpha, MIP-1beta, and RANTES
      were detected, while none or only minimal secretion of these CC-chemokines was
      observed in three IL-4- and IL-5-producing Th2 cell clones.

PMID- 8871661
TI  - Regulation of polymorphonuclear leukocyte cytokine receptor expression: the role
      of altered oxygen tensions and matrix proteins.
AB  - We investigated the effects of hypoxemia +/- reoxygenation (H/R) on matrix
      protein regulation of polymorphonuclear leukocyte (PMN) IL-1beta types I and II,
      TNF-alpha (p60, p80), and IL-8R expression compared with normoxic controls. H/R
      reduction IL-1beta type I, TNF-alpha (p80), and IL-8R expression compared with
      hypoxic levels. Neither fibronectin nor laminin effected cytokine receptor
      expression during normoxia, but both fibronectin and laminin significantly
      reduced IL-1beta type I, TNF-alpha (p80), and IL-8R expression during hypoxia.
      Following H/R, both fibronectin and laminin significantly reduced IL-1beta type
      I, TNF-alpha (p80), and IL-8R expression during hypoxia. Following H/R, both
      fibronectin and laminin significantly increased TNF-alpha (p60, p80) and IL-8R
      expression. Cross-linking of adherent PMN very late antigen (VLA)-5 and VLA-6
      receptors resulted in a progressive increase in TNF-alpha (p60, p80) and IL-8R
      expression during hypoxia; cross-linking of adherent PMN VLA-5 and and VLA-6
      receptors resulted in a progressive increase in TNF-alpha (p60, p80) and IL-8
      receptors following H/R. Cross-linkage of IL-1betaR type I, TNF-alphaR (p80), and
      IL-8R during hypoxia and H/R resulted in increased and subsequently decreased O2-
      production and degranulation. Inhibition of reduced nicotinamide adenine
      dinucleotide phosphate oxidase activation with diphenyleneiodonium following
      hypoxia but before reoxygenation prevented the decreases in IL-1beta types I and
      II, TNF-alpha (p80), and IL-8R expression that was seen following H/R alone.
      These results demonstrate that, during hypoxia and H/R, integrin signaling via
      alpha5beta1, and alpha6beta1 increases and subsequently decreases the expression
      of PMN cytokine receptors.

PMID- 8871663
TI  - Recombinant human IL-11 attenuates the inflammatory response through down
      regulation of proinflammatory cytokine release and nitric oxide production.
AB  - To elucidate the molecular mechanisms regulating the anti-inflammatory activities
      of recombinant human (rh)IL-11, the ability of rhIL-11 to reduce serum levels of
      inflammatory mediators such as TNF-alpha, IL-1beta, IL-12, and IFN-gamma in LPS
      treated mice and to down-regulate macrophage function in culture was
      investigated. In a mouse model of endotoxemia, pretreatment with rhIL-11 blocked
      LPS-induced elevation of TNF-alpha, IL-1beta, and IFN-gamma serum levels, but had
      no effect on IL-12 p40, IL-6, or IL-10 serum levels. The effects of rhIL-11 on
      the production of inflammatory mediators in vivo may occur in part through direct
      interactions with macrophages. rhIL-11 pretreatment of thioglycollate-elicited
      peritoneal macrophages resulted in greater than 60% inhibition of LPS-induced
      production of TNF-alpha, IL-1beta, IL-12 p40, and nitric oxide. The activity of
      rhIL-11 was not mediated through induction of IL-10, IL-6, or TGF-beta1. These
      results indicate that the ability of rhIL-11 to modulate the inflammatory
      response is not dependent on known anti-inflammatory cytokines and substantiate a
      role for this cytokine in the attenuation of inflammatory conditions.

PMID- 8871662
TI  - CD63 associates with tyrosine kinase activity and CD11/CD18, and transmits an
      activation signal in neutrophils.
AB  - As a member of the tetraspan family, it has been hypothesized that CD63 may be
      associated with signal transduction; however, its role in leukocyte function is
      unknown. To examine the potential ability of CD63 to activate neutrophils, the
      effects of five CD63 mAbs, AHN-16, -16.1, -16.2, -16.3, and -16.5, were examined
      for their ability to alter neutrophil adhesion to HUVEC monolayers. These CD63
      Abs increased neutrophil adhesion to resting and TNF-stimulated HUVEC monolayers.
      This increase in neutrophil adhesion caused by CD63 Abs was blocked by a CD18 Ab
      and was associated with up-regulation of CD11/CD18 and down-regulation of CD62L
      on the neutrophil surface. CD11/CD18 was also found to be associated with CD63.
      This increase in neutrophil adhesion required physiologic extracellular calcium
      concentrations at or near the time of CD63 Ab binding. The incubation of CD63 Abs
      with cells in the absence of calcium for 10 min before repletion of calcium
      resulted in no increase in neutrophil adhesion. Protein kinase activity was
      detected in neutrophils associated with CD63. Most of the protein kinase activity
      associated with these Ags was tyrosine kinase activity, with a lesser amount of
      threonine and serine kinase activities. Src family kinases Lyn and Hck accounted
      for much of the associated tyrosine kinase activity. The data suggest that CD63
      Ab binding to the neutrophil surface triggers a transient activation signal that
      requires extracellular calcium and regulates the adhesive activity of CD11/CD18.
      Associated protein kinase activity may play a role in signal transduction by CD63
      to regulate other cell functions.

PMID- 8871664
TI  - Reverse signaling via CD30 ligand.
AB  - CD30 ligand (CD30L), a member of the TNF family, is a type II membrane protein
      with a C-terminal extracellular domain that is homologous with the extracellular
      domains of other TNF family members. Also, like most TNF family members, the N
      terminal cytoplasmic domain of CD30L is conserved across species, but not between
      family members, suggesting a possible biological function. Motivated by this
      observation, we investigated the potential for CD30L, when activated by cross
      linking, to directly transduce a signal to the ligand-bearing cell. Cross-linking
      of CD30L by a mAb or by CD30-Fc fusion protein induced the production of IL-8 by
      freshly isolated neutrophils. Further, both cross-linking mechanisms produced a
      rapid oxidative burst. Indirect effects through CD30 were ruled out, since CD30L,
      but not CD30, is expressed on neutrophils. Expression of CD30L can be induced in
      peripheral blood T cells by cross-linking the CD3 component of the TCR.
      Peripheral blood T cells exposed to suboptimal concentrations of anti-CD3
      increased metabolic activity, proliferated, and produced IL-6 in response to
      cross-linking of CD30L. These results indicate that cross-linked CD30L can
      transduce a signal to the ligand-bearing cell. This "reverse signaling" via CD30L
      taken together with previously published data concerning other ligands in the TNF
      family strongly suggest that, as a rule, TNF family members and their cognate
      receptors signal bidirectionally, blurring the distinction between ligand and
      receptor.

PMID- 8871665
TI  - IgE autoantibodies directed against the major bullous pemphigoid antigen in
      patients with a severe form of pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease
      characterized in part by circulating and tissue-bound IgG autoantibodies directed
      against the basement membrane zone. In addition, most of the patients with BP
      have increased serum IgE levels which seem to be correlated with the disease
      activity, whereas the presence of circulating anti-basement membrane zone IgE Abs
      has been reported in some patients. To elucidate whether IgE-dependent mechanisms
      play a role in the physiopathology of BP, we looked for the presence of IgE Abs
      specifically directed against the major BP Ag (BPAg1) in sera of BP patients at
      the onset and after remission of the disease. A radioimmunoassay and a 55-kDa
      recombinant protein (rBP55) obtained from a cDNA sequence, encoding the C
      terminal region of the BPAg1 and containing the BPAg1 immunodominant epitopes,
      were used. Anti-rBP55 IgE Abs were found in 12 of the 19 sera tested. When the
      patients were divided into two groups according to the disease severity, anti
      rBP55 IgE Abs were found only in patients with a severe form of the disease.
      Cytophilic IgE was detected on approximately 20% of peripheral blood eosinophils
      purified from BP patients. Immunohistochemistry studies suggested that some of
      the IgE-bearing cells in the lesional skin of BP patients are eosinophils.
      Immunostaining experiments revealed the existence of FcepsilonRI on both
      peripheral blood and tissue eosinophils. Taken together, these results suggest
      that IgE-dependent mechanisms could participate in the constitution of the
      lesions in BP.

PMID- 8871666
TI  - Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in
      combination with other C6 and C7 deficiencies.
AB  - Combined subtotal deficiency of C6 and C7, in which both proteins are expressed
      at very low levels, has been observed in homozygous form in two families. A
      defect at the 5' splice donor site of intron 15 of the C6 gene explains the low
      molecular weight of the C6 protein and is probably responsible for its low
      expressed concentration. The C7 defect is more enigmatic: the protein is of
      normal molecular weight, low circulating concentration, and altered isoelectric
      point. An Arg > Ser codon substitution in exon 11 is the only molecular
      alteration within the mature C7 protein. These defects are associated with a
      characteristic set of polymorphic DNA markers in the C6/C7 region, forming a
      distinct haplotype. The haplotype has been found in combination with a number of
      other haplotypes containing defective genes that lead either to C6 or C7
      deficiency, but with different consequences. Where it is combined with a C6
      deficient gene, the serum C7 levels can be surprisingly high, possibly because
      there is no C6 generating C56 to consume the C7. In contrast, where the C7 genes
      are both defective (but still partially functional), there may be a profound
      deficit of circulating C7 because there is ample C6 to produce C56 and consume
      the already small amount of C7. Each molecular defect has also been found in
      isolation and has the expected effect.

PMID- 8871667
TI  - Env-specific CTL predominate in cats protected from feline immunodeficiency virus
      infection by vaccination.
AB  - Animal models of HIV-1 have a key role to play in elucidation of the cellular
      mechanisms responsible for protective immunity. Vaccination of domestic cats with
      whole inactivated feline immunodeficiency virus (FIV) elicits virus-neutralizing
      Abs and virus-specific CTL in the peripheral blood and lymphoid organs and
      affords protection from homologous virus challenge. In the present study we
      confirm the induction of virus-specific CTL following immunization with whole
      inactivated FIV vaccine and demonstrate that cats are protected for up to 1 yr
      following vaccination. Long term protection in vaccinated cats correlates with
      both higher levels of FIV Env-specific CTL in the peripheral blood following
      vaccination and the presence of FIV Env-specific memory CD8+ CTL in the lymph
      nodes, which persist for up to 1 yr following challenge in the absence of
      detectable virus. The CTL responses observed in vaccinated protected cats differ
      qualitatively from those in FIV-infected cats. The latter cats either do not
      generate a memory CTL response or exhibit a Gag-specific memory CTL response.
      These results show that the protective immunity observed in whole inactivated
      virus-vaccinated cats is associated with the induction of high levels of Env
      specific CTL activity.

PMID- 8871668
TI  - Molecular characterization of properdin deficiency type III: dysfunction produced
      by a single point mutation in exon 9 of the structural gene causing a tyrosine to
      aspartic acid interchange.
AB  - Inherited properdin deficiency is an X-linked recessive disorder clinically
      manifested by susceptibility to meningococcal disease. Deficiency of properdin is
      characterized by complete absence (type I), very low level presence (type II), or
      the presence of a dysfunctional properdin protein in serum as found in one Dutch
      family (type III). To better understand the dysfunctional protein on the
      molecular level, samples from three members of the Dutch family were analyzed by
      direct genomic sequencing. The sequence of the complete gene, including 10 exons
      and 9 introns, covering about 6500 bases was determined. The dysfunctional
      properdin was found to be caused by a single T to G mutation in exon 9, which
      gives rise to a substitution of a tyrosine by an aspartic acid residue at
      position 387. This change to a hydrophilic amino acid affects the function of the
      properdin molecule, although the oligomerization of dysfunctional properdin
      molecules was similar to that of normal properdin. In binding studies with C3b
      and properdin in serum, no properdin deposition was detected with the type III
      deficient serum. Inhibition studies with different decapeptides revealed distinct
      inhibitory sequences, and indicated also that the part of properdin containing
      the type III mutation was not directly involved in the binding to C3b. The
      mutation most likely causes conformational changes that make the properdin
      molecule dysfunctional by affecting its binding to C3b.

PMID- 8871669
TI  - Regulation of surface and soluble TNF receptor expression on human monocytes and
      synovial fluid macrophages by IL-4 and IL-10.
AB  - By regulating monocyte and macrophage production of IL-1, its receptor, and its
      receptor antagonist, IL-4 and IL-10 may exert significant anti-inflammatory
      activity. We determined whether a similar multicomponent process controlling TNF
      activity was regulated by IL-4 and IL-10 in nonadherent monocytes and synovial
      fluid macrophages. Previous studies differed in their conclusions. For both the
      p75 and p55 TNF receptors, mRNA levels, surface receptor expression, and soluble
      receptor levels were measured for blood monocytes incubated in vitro for 17, 40,
      or 64 h with IL-4 or IL-10. The predominant TNF receptor on monocytes, the p75
      receptor, was down-regulated by IL-4 at the mRNA level. In turn, both surface and
      soluble receptor levels on LPS-stimulated cells were reduced and the inhibitory
      effects were maintained for at least 64 h. In contrast, IL-10 increased surface
      and soluble p75 TNF receptor levels on monocytes for approximately 40 h, which
      reflected an increase in receptor mRNA. These studies suggest that IL-4 and IL-10
      do not directly regulate the cleavage of TNF receptors from monocytes and
      macrophages. Addition of an Ab to IL-10 suggested that the stimulatory effects of
      LPS on p75 TNF receptor expression were due, at least in part, to LPS stimulation
      of IL-10 production and that IL-4 acted, in part, by decreasing IL-10 production.
      IL-4 was down-regulatory and IL-10 stimulatory for TNF receptor expression by
      synovial fluid macrophages. By increasing surface receptor levels, IL-10 enhanced
      the activities of TNF on monocytes for IL-1beta production. By increasing soluble
      TNF receptor levels, IL-10 may limit only temporarily the activity of other TNF
      responsive cells. This study questions the benefit of IL-10 to resolving TNF
      associated inflammation.

PMID- 8871670
TI  - IL-15 stimulates the expansion of AIDS virus-specific CTL.
AB  - It has been assumed that the maturation of pre-CTL to virus-specific effector CTL
      is dependent upon IL-2-mediated T cell triggering through the IL-2R. In view of
      its similarity to IL-2 in its effects on immune cells, we sought to determine
      whether IL-15 can induce the expansion of AIDS virus-specific pre-CTL to mature
      CTL. PBL of SIV(mac)-infected rhesus monkeys or HIV-1-infected humans have
      previously been shown to expand to effector CTL when cultivated with a predicted
      CTL epitope peptide and rIL-2. We now demonstrate that rIL-15 facilitates this
      expansion of effector CTL. In fact, rIL-15-driven expansion of virus-specific CTL
      occurs in the presence of IL-2-neutralizing or anti-IL-2R Abs, indicating that
      this cellular maturation can occur in an IL-2-independent fashion. These studies
      suggest a mechanism by which CTL may be capable of expanding in vivo in the
      absence of IL-2 and functional CD4+ T lymphocytes.

PMID- 8871671
TI  - RIP-beta 2-microglobulin transgene expression restores insulitis, but not
      diabetes, in beta 2-microglobulin null nonobese diabetic mice.
AB  - Beta2m-deficient nonobese diabetic (NODbeta2mnull) do not develop insulitis or
      diabetes. Expression of a beta2m transgene controlled by the rat insulin promoter
      (RIP-beta2m) in NODbeta2mnull mice resulted in reconstitution of IFN-gamma
      inducible cell surface MHC class I protein on pancreatic beta-cells. These mice
      developed insulitis, but did not develop diabetes. Transfer of T cells from
      diabetic NOD mice to NODbeta2mnull recipients resulted in insulitis, which took
      several months to progress to diabetes. In contrast, transgenic RIP
      beta2m/NODbeta2mnull mice with islet MHC class I reconstitution developed
      diabetes rapidly after transfer of diabetic NOD spleen cells. Administration of
      cyclophosphamide, which accelerates diabetes in NOD mice, resulted in 43% of
      RIPbeta2m/NODbeta2mnull mice becoming diabetic compared with 75% of wild-type
      mice and 0% of NODbeta2mnull mice. Acceleration of diabetes by cyclophosphamide
      was prevented by anti-CD8 mAb treatment. FACS analysis of peripheral blood and
      lymphoid organs from transgene-bearing animals did not show an increase in the
      number of CD8+ T cells compared with that in NODbeta2mnull mice. In summary, beta
      cell expression of beta2m in NODbeta2mnull mice resulted in a return of
      insulitis, but not spontaneous diabetes. These studies demonstrate that beta2m
      and cell surface MHC class I expression on beta-cells are essential for the
      initiation of diabetes in the NOD mouse and further confirm that efficient
      progression to diabetes requires both CD4+ and CD8+ T cells.

PMID- 8871672
TI  - The immune response to 52-kDa Ro and 60-kDa Ro is linked in experimental
      autoimmunity.
AB  - Clustering of autoantibody specificities is a consistent finding in patients with
      systemic autoimmune diseases. Patients with Sjogren's syndrome frequently have
      autoantibodies to La, 60-kDa Ro(SS-A) protein (Ro60), and 52-kDa Ro(SS-A) protein
      (Ro52). In the case of anti-Ro60 and anti-La, there is evidence that these
      specificities occur together because of the physical association of the Ro60 and
      La proteins that form a ribonucleoprotein particle (RNP). Thus, the autoantibody
      response may spread from a single epitope to involve new epitopes located within
      other components of the RNP. The physical association of Ro52 with the Ro/La RNP
      has remained controversial, implying that Abs to Ro52 are not a consequence of
      intermolecular spreading and may be triggered independently of the anti-Ro60
      response. To examine this relationship of the immune response to Ro52 and Ro60,
      mice were immunized with recombinant Ro52, Ro60, or La, and examined for
      autoantibody production. Immunization with Ro52 resulted in rapid, high titer Ab
      production to Ro52, followed 7 to 14 days later by lower titer autoantibody
      production to Ro60. Immunization with Ro60 led to anti-Ro60, which was also
      followed 7 to 14 days later by a lower titer anti-Ro52 response. Cross-reactivity
      of affinity-purified Abs from immune mouse sera was not observed. These
      observations suggest that the autoimmune responses to Ro60 and Ro52 are linked
      intrinsically, despite previous evidence suggesting they are not associated in
      vivo. The mechanism of linkage remains unclear, but the data are most consistent
      with some physical association of Ro52 and Ro60 allowing autoimmunization,
      presumably as a result of normal cell turnover or specific injury in vivo.

PMID- 8871673
TI  - Ex vivo treatment of antigen-presenting cells with CTLA4Ig and encephalitogenic
      peptide prevents experimental autoimmune encephalomyelitis in the Lewis rat.
AB  - We used a novel approach to study the role of CD28-B7 T cell costimulatory
      blockade in experimental autoimmune encephalomyelitis (EAE) in the Lewis rat
      model. APCs were incubated in vitro with CTLA4Ig and the encephalitogenic peptide
      p71-90 of myelin basic protein. Systemic injection of APCs treated ex vivo with
      p71-90 and CTLA4Ig before immunization protected animals from clinical EAE.
      Systemic injection of APCs treated with CTLA4Ig alone, CTLA4Ig and control
      peptide, peptide alone, or peptide and control Ig was not protective. Injection
      of APCs treated ex vivo with CTLA4Ig and p71-90 on the day of immunization was
      also protective, but delaying the injection till day 7 after immunization
      impaired the protective effect. Immunohistologically, protected animals had
      decreased inflammatory responses, with inhibition of Th1 and sparing of Th2
      cytokines in the brain. Preincubation of APCs with p71-90 and a mutant form of
      CTLA4Ig that binds only B7-1 also protected animals from developing EAE. These
      results suggest that ex vivo blockade of CD28-B7-1 leads to the generation of
      regulatory cells, presumably Th2, which inhibit the generation or priming of
      encephalitogenic T cells and suppress the autoimmune response to the specific Ag
      in vivo. These observations have therapeutic implications for autoimmune diseases
      and transplantation.

PMID- 8871674
TI  - A CD4-CDR3 peptide analog inhibits both primary and secondary autoreactive CD4+ T
      cell responses in experimental allergic encephalomyelitis.
AB  - A structure-based design approach was used to develop a cyclized peptide analog
      of the murine CD4-CDR3-like region as a potential inhibitor of autoimmune CD4+ T
      cells responsible for the pathogenesis of experimental allergic encephalomyelitis
      (EAE). Our results indicate that this peptide, referred to as rD-mPGPtide, is
      able to significantly inhibit the clinical and pathologic symptoms of EAE in the
      SJL mouse model when administered on day 12 of induction. The optimum effective
      dosage range for the peptide, injected i.v., was between 0.125 and 0.5 mg and
      dosages of as high as 5 mg had no observable toxic effects. Treated mice had
      normal levels of lymphocytes less than 2 wk later and exhibited normal in vitro
      primary responses to alloantigen and secondary responses to keyhole limpet
      hemocyanin Ag. The specificity of the rD-mPGPtide treatment for autoreactive T
      cells was demonstrated by inhibiting proteolipid protein (p139-151)-induced EAE
      and finding that the lymph node T cells from these mice had suppressed responses
      to this Ag, but normal responses to alloantigen or other nominal Ag. Importantly,
      rD-mPGPtide was found to be effective on secondary T cell responses in an EAE
      rechallenge situation and was able to establish conditions for long-term
      resistance to further Ag exposure. Analysis of the cytokine profile of responding
      T cells during late effector stages of disease revealed that the levels of IFN
      gamma and IL-4 are significantly reduced in rD-mPGPtide-treated mice. These
      results strongly suggest that the administration of a CD4-CDR3 peptide analog is
      an effective therapeutic approach for the inhibition of the CD4+ T cell-mediated
      autoimmune response in EAE.

PMID- 8871675
TI  - High density insulin receptor-positive T lymphocytes from nonobese diabetic mice
      transfer insulitis and diabetes.
AB  - In the nonobese diabetic mouse, insulin-dependent diabetes is an autoimmune
      disease characterized by T cell-mediated invasion and destruction of pancreatic
      islet beta cells. The importance of insulin receptor (IR) expression in the
      pathogenesis of diabetes was examined, since it has been shown that the IR is a
      chemotactic receptor capable of directing cell movement in response to insulin.
      Using polyclonal antisera to the IR, phenotypic analysis of purified splenic T
      cells from diabetic mice showed that about 15% of T cells expressed high density
      IR (IRhigh). In addition, IRhigh T cells were already a dominant phenotype in the
      insulitis of young prediabetic mice. To determine the ability of IRhigh T cells
      to transfer diabetes, cells were sorted by flow cytometry before adoptive
      transfer into young (6- to 8-wk-old) nondiabetic irradiated nonobese mice.
      Transfer of as few as 3 x 10(6) purified IRhigh T cells alone resulted in rapid
      onset of insulitis and diabetes, and IRhigh-depleted T cells were essentially
      unable to passage either insulitis or diabetes. The adoptive transfer of disease
      was not due to the transfer of activated cells, since removal of IL-2R+ or
      transferrin R+ cells did not alter diabetes transfer. Therefore, IRhigh T cells
      are aggressively diabetogenic, suggesting that increased IR expression may
      provide a mechanism for delivering potentially autoreactive T cells to the islet,
      regardless of their activation state.

PMID- 8871676
TI  - Nonrheumatoid IgM in human hepatitis C virus-associated type II cryoglobulinemia
      recognize mimotopes of the CD4-like LAG-3 protein.
AB  - Type II mixed cryoglobulinemia (CryoII) is an autoimmune disorder frequently
      associated to human hepatitis C virus (HCV) infection and characterized by the
      presence of cold-insoluble immunocomplexes containing IgM with rheumatoid
      activity. To identify disease-related epitopes, we screened a phage-displayed
      random peptide library using purified IgM from patients with HCV-associated
      CryoII(CryoII/HCV). A dominant population of phage isolates bearing the HPLAP
      pentapeptide consensus motif was identified and shown to be recognized by a
      nonrheumatoid IgM species strongly associated to CryoII/HCV. The phage-borne
      mimotopes (phagotopes) displayed a strong homology with an exposed extra-loop
      region of human lymphocyte activation 3 gene (LAG-3) product. Consistently,
      rabbit sera raised against a synthetic LAG-3 peptide efficiently recognized the
      selected phagotopes. Furthermore, one such phagotope was revealed to be a good
      immunogenic mimic of LAG-3 when injected into rabbits. IgM purified from
      CryoII/HCV patients' sera specifically reacted with the LAG-3 peptide in ELISA,
      and this binding was inhibited by the selected phagotopes. These results provide
      experimental support for a general strategy to identify novel autoantigens.

PMID- 8871677
TI  - Induction of tolerance in murine autoimmune diabetes by transient blockade of
      leukocyte function-associated antigen-1/intercellular adhesion molecule-1
      pathway.
AB  - The present study demonstrated that a short-term administration of mAbs against
      leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion
      molecule-1 (ICAM-1) at critical periods resulted in complete protection of
      autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were
      administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was
      observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s)
      was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective
      suppressor activity was not enough to prevent diabetes because co-transfer of
      splenocytes from female NOD mice, which had received these mAbs at 2 wk of age,
      resulted in only a short delay of the diabetic onset caused by adoptive transfer
      of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to
      young NOD mice could not also abrogate the spontaneous diabetes and insulitis.
      Furthermore, cyclophosphamide treatment could not abrogate the protection. When
      splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of
      the recipient mice developed significant insulitis and subsequent overt diabetes,
      suggesting the absence or the inactivation of diabetogenic effector T cells.
      However, splenic T cells from the insulitis-free NOD mice that had received the
      mAb treatment preserved proliferative responses to both islet cells and 65-kDa
      glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique
      peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1
      pathway in an early age of NOD mice.

PMID- 8871678
TI  - Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a
      cluster of lysine residues that are critical for phospholipid binding and anti
      cardiolipin antibody activity.
AB  - beta2-Glycoprotein I (beta2GPI) is a phospholipid-binding serum protein with
      anticoagulant properties. It plays a vital role in the binding of anti
      cardiolipin Abs purified from patients with autoimmune disease when assayed in a
      cardiolipin (CL) ELISA. Based on a three-dimensional model of beta2GPI,
      electrostatic calculations, and earlier peptide studies, a highly positively
      charged amino acid sequence, Lys282-Asn-Lys-Glu-Lys-Lys287, located in the fifth
      domain of beta2GPI, has been predicted to be the phospholipid binding site. We
      tested this hypothesis by site-directed mutagenesis of residues in the predicted
      phospholipid binding site and by assessing the mutants for phospholipid binding
      and anti-beta2GPI activity. A single amino acid change from Lys286 to Glu
      significantly decreased the binding of beta2GPI to CL. Double and triple mutants
      2k (from Lys286, 287 to Glu286, 287), 2ka (from Lys284, 287 to Glu284, 287), and
      3k (from Lys284, 286, 287 to Glu284, 286, 287) possessed no binding of Ab to
      beta2GPI in a CL ELISA, as well as no inhibitory activity on the binding of
      iodinated native beta2GPI to CL. These results indicate that the residues Lys284,
      Lys286, and Lys287 in the fifth domain of beta2GPI are critical for its binding
      to anionic phospholipids and its subsequent capture for binding of anti-beta2GPI
      Abs.

PMID- 8871679
TI  - Expression of acetylcholine receptor genes in human thymic epithelial cells:
      implications for myasthenia gravis.
AB  - The intrathymic presence of the muscle acetylcholine receptor (AChR) is
      controversial, and the nature of the cell(s) expressing it is unclear. We thus
      analyzed the molecular expression of muscle AChR in human thymi. mRNA studies
      indicated that the two isoforms (P3A+ and P3A-) of the alpha-subunit were present
      in thymic extracts and in cultured thymic epithelial cells (TEC), while
      expression in thymocytes was low and not consistently detectable. The amount of
      mRNA coding for the alpha-subunit, evaluated by means of quantitative PCR, was
      about 20 times less in TEC than in muscle, and was similar in TEC from normal
      subjects and from patients with myasthenia gravis (MG). The beta- and epsilon
      subunits present in adult AChR were also expressed in TEC (but not in
      thymocytes), while the embryonic subunit (gamma) was absent. In TEC cultures, the
      AChR alpha- and epsilon-subunit mRNA levels were down-regulated by forskolin, as
      also observed in the TE671 rhabdomyosarcoma cell line, suggesting similar
      regulation of AChR subunits in thymus and muscle. Protein expression was
      evidenced on TEC (but not on thymocytes), by Western blotting as well as by
      immunofluorescence, thus demonstrating AChR expression on human thymic epithelial
      cells. There was no difference in the expression of AChR between TEC from MG
      patients and controls, meaning that the expression of AChR subunits alone is not
      sufficient to explain the onset of MG.

PMID- 8871680
TI  - Water-borne pollutants.

PMID- 8871681
TI  - Weighing contaminant risks and nutrient benefits of country food in Nunavik.
AB  - In view of the levels of human exposure to priority contaminants assessed in
      previous surveys in Nunavik, a series of risk reduction scenarios were produced
      to modelize the effects of different potential health advisories on limiting
      exposure of women of reproductive age to these contaminants, as well as on
      maximizing nutritional benefits derived from the consumption of country food.
      This paper presents part of the results, in particular as regards effects of
      reducing PCB intake by 46%, 65% and 86%.

PMID- 8871683
TI  - Cardiovascular disease and environmental pollutants: the Arctic aspect.
AB  - Environmental pollution in the Arctic is due to long range transport from lower
      latitudes or to local industrial activities. Since the latter are not different
      from point source exposure in the rest of the world the paper focuses on the
      former aspect which is the main type of environmental pollution in the western
      Arctic. The environmental pollutants of major significance are heavy metals
      (mercury, cadmium, lead) and persistent organic pollutants (PCB's, pesticides)
      and the main exposure is through the traditional diet of sea mammals (mercury,
      cadmium, persistent organic pollutants) and through smoking (cadmium). There is
      rather strong evidence that lead is a (weak) risk factor for high blood pressure
      even at low levels of exposure. Apart from lead there is little evidence that the
      above mentioned pollutants are significantly related to cardiovascular diseases.
      Since the pollutants, however, are found in the traditional diet together with n
      3 polyunsaturated fatty acids, monounsaturated fatty acids, and selenium which
      are believed to promote cardiovascular health there is an indirect link between
      the pollutants and cardiovascular disease. This becomes relevant when dietary
      guidelines are developed for arctic populations. Epidemiological evidence from
      Greenland relevant for this discussion is presented, i.e. i) findings from a
      countrywide interview survey on dietary habits which show that sea mammals are
      widely consumed and appreciated for health and other reasons and that there is
      virtually no fear of pollution, and ii) mortality results which do not support
      the hypothesis that the low rate of ischemic heart disease in Inuit is due to
      their traditional diet.

PMID- 8871682
TI  - The Inuit diet. Fatty acids and antioxidants, their role in ischemic heart
      disease, and exposure to organochlorines and heavy metals. An international
      study.
AB  - Traditional food is culturally, economically and nutritionally important for the
      Greenlandic Inuit people. In the 1970s the preventive effect of marine fat on
      cardiovascular disease, thrombosis and atherosclerosis was described. The low
      incidence of ischemic heart disease among Greenlanders has been related to the
      high intake of marine food. Since 1990 routine autopsies have taken place in two
      towns in Greenland, Nuuk and Ilulissat. The autopsies represent 26% of the total
      number of deaths in these two towns. Samples have been collected from 104
      autopsies. International cooperative studies have analysed specimens in relation
      to ischemic heart disease as a benefit related to diet, as well as the level of
      heavy metals and organochlorine in organs as a risk related to diet. High amounts
      of mono-unsaturated and Omega-3 poly-unsaturated fatty acid were found in adipose
      tissue. Liver analyses of selenium have confirmed the expected high intake among
      Greenlanders. Reduced atherosclerotic lesions were found in the coronary
      arteries. Blood pressure levels calculated from renovascholopathia of
      hypertension indicate prevailing levels similar to those in industrialized
      countries. Some factors in Greenland may be protecting the coronary arteries,
      thereby of setting the expected effect of hypertension. The level of methyl
      mercury in organs is generally high. PCB concentrations found in organs of
      Greenlanders are higher than among other populations. Health and risk effects of
      the traditional foods need further investigation.

PMID- 8871684
TI  - Radioecology and and the health of the indigenous inhabitants in Chukotka.

PMID- 8871685
TI  - Fertility and environmental pollutants with reference to male fecundity.

PMID- 8871687
TI  - Meetings and the irresponsible use of time.

PMID- 8871686
TI  - Preliminary report of trace elements in mothers and newborns living in the Kola
      Peninsula and Arkhangelsk region of Russia compared to Norwegian populations.
AB  - Recently, considerable attention has been allotted to the possible health effects
      of the industrial pollution in the regions adjoining the Norwegian-Russian
      border. As a measure of general health, the status of trace elements and some
      clinical-chemical parameters in serum and blood that reflect general health was
      assessed for 50 consecutive obstetric patients presenting at delivery departments
      of local hospitals in the Kola Peninsula, Arkhangelsk and selected centres in
      Norway. A written questionnaire and consent form were completed by each
      participant. Specimens of maternal and cord blood were collected. Corresponding
      samples were analyzed for copper, zinc, selenium, iron and ferritin. We found a
      lower birth weight in the Russian centres. The measurement of trace elements
      showed a higher iron status for the Russian females and relatively low serum zinc
      levels were observed in both the Russian and the Norwegian communities. It may be
      concluded that with the exception of zinc, the mineral status in the Norwegian
      and Russian arctic centres considered appears to be satisfactory.

PMID- 8871688
TI  - A call to authenticity--Part 2.

PMID- 8871689
TI  - Nursing and the "politics of meaning".

PMID- 8871690
TI  - Yale and Edinburgh universities' nursing education pioneers.

PMID- 8871691
TI  - Are the humanities still relevant in nursing today?

PMID- 8871692
TI  - Boyer's multidimensional nature of scholarship: a new framework for schools of
      nursing.
AB  - This article compares Boyer's concept of four dimensions of scholarship with
      nursing's traditional definition of scholarship. A case is made that Boyer's
      concept is congruent with nursing's present and future direction of scholarship.
      An example is given of how one school of nursing has used Boyer's concept as a
      framework to develop policies and practices to promote and reward the scholarship
      of discovery, integration, application, and teaching.

PMID- 8871693
TI  - Nurse faculty job satisfaction: a national survey.
AB  - Faculty dissatisfaction and fewer qualified recruits choosing a career in
      academia threaten the integrity of the higher education system. Retention of
      highly qualified nurse faculty affects the reputation of the school of nursing,
      the faculty commitment to the organization, and the learning environment for
      students. Through use of a system's framework derived from Neuman and Kast and
      Rosenzweig, the purpose of this survey was to ascertain the relationship between
      job satisfaction among nurse faculty and selected demographic variables,
      organizational characteristics, and role orientation. Approximately 80 per cent
      of the schools of nursing in the target population of universities offering a
      doctorate in nursing participated in the study. The overall subject response rate
      was 60 per cent. Instruments used for data collection included three researcher
      developed tools and two standardized instruments to measure job satisfaction (the
      Job Descriptive Index and the Job in General Scale). Significant correlations (P
      < .05) emerged between each of the demographic variables and at least one of the
      criterion measures of job satisfaction. In addition to descriptive statistics and
      correlation analysis, a stepwise linear regression-correlation analysis showed
      that salary, degree level of nursing students taught, and length of annual
      contract were significant indicators of nurse faculty job satisfaction.

PMID- 8871694
TI  - Education for entry into practice: an ethical perspective.
AB  - Educational preparation for entry into nursing practice is an issue that has been
      the subject of intense debate among nursing educators and leaders, but it has yet
      to be resolved. This issue is surrounded by practice, licensure, and education
      dilemmas that are examined from an ethical perspective. The ethical principles of
      justice, fidelity, and utility are informed by an ethic of care and are used to
      analyze the implications of this issue and its associated dilemmas for the
      nursing student and graduate, the client and society, and the profession. Moral
      questions are raised that must be answered by nursing educators because the
      status quo in nursing practice, licensure, and education is morally unacceptable.

PMID- 8871695
TI  - Developing an ethical basis for student-teacher interaction.
AB  - This article first reviews the literature on the development of ethical content
      within nursing curricula and its impact on nursing education. This is followed by
      a discussion of faculty responsibility for the preparation of ethically competent
      graduates. Faculty behaviors that appear to be related to ethically sound
      education practices are discussed along with examples of positive and negative
      behaviors. The article concludes with five principles to use in developing an
      ethical basis for student-teacher relationships. These principles include mutual
      respect, open communication, demonstration of linkages between ethical principles
      and behavior, facilitating students' understanding of their behaviors, and
      recognition of legitimate individual differences in ethical positions.

PMID- 8871696
TI  - Doctoral education in community health nursing: a national survey.
AB  - The purpose of this study was to identify content areas specific to community
      health nursing in doctoral programs throughout the United States. The research
      foci related to community health nursing were compared with previously identified
      research priorities in the field. Surveys were sent to 52 doctoral program
      directors; 23 questionnaires were completed. Telephone interviews were conducted
      with 16 program directors to clarify responses. Newer programs tended to be more
      generally focussed and without doctoral specialty courses of any kind. The four
      programs that identified community health nursing as a specialty within their
      curriculum were some of the oldest and largest programs in the country.

PMID- 8871697
TI  - An evolutionary concept analysis of mentoring in nursing.
AB  - Despite widespread evidence of the concept of mentoring in nursing, it has been
      largely undefined, borrowed from other disciplines, viewed as static, and/or
      confused with related terms. Building on the work of Yoder and using a literature
      based method developed by Rodgers, an evolutionary concept analysis is presented
      to provide an understanding of the meaning of mentoring in nursing, its current
      status, and the conceptual clarity necessary for additional systematic and
      rigorous inquiry. A random sample of 82 research abstracts and journal articles,
      representing 26 per cent of the total population of literature, was used to
      extract six essential attributes of the concept: a teaching-learning process, a
      reciprocal role, a career development relationship, a knowledge or competence
      differential between participants, a duration of several years, and a resonating
      phenomenon. These attributes form the theoretical definition of mentoring in
      nursing. Antecedents, consequences, related concepts, and empirical referents are
      presented. A model case, encompassing all of the critical attributes, depicts the
      Investigators' mentoring experience. Major changes in mentoring are viewed within
      the context of nursing as a learned profession, a legitimate academic enterprise,
      and a clinical science. Implications for further development are posed to further
      mentoring as a process for the socialization of nurse scholars and scientists and
      the proliferation of a body of professional knowledge.

PMID- 8871698
TI  - Clinical inference by nursing students and experienced nurses concerning harmful
      outcomes occurring after medication errors: a comparative study.
AB  - Clinical inference is part of the clinical decision-making process and precedes
      judgment and action. It is an integrated response to patient cues and other
      evidence and a necessary skill for all nurses. The purpose of this study was to
      compare undergraduate and graduate nursing students' use of clinical inference in
      rating harmful outcomes for patients occurring after medication errors. The
      Medication Error Outcome Scale, a simulation methodology using medication error
      vignettes, was used to compare undergraduate and graduate students' use of
      clinical inference. Kruskal-Wallis analysis of variance showed that there was a
      statistically significant difference (P = .04) among freshman, junior, senior,
      baccalaureate, and Master's students' use of clinical inference in regard to
      perceived harm occurring after a medication errors. Post hoc Mann-Whitney U tests
      indicated that senior and baccalaureate students' use of clinical inference
      differed significantly (P = .005). This study suggests that clinical experience
      shapes clinical inference.

PMID- 8871699
TI  - Licensure of international students. American Association of Colleges of Nursing.

PMID- 8871700
TI  - Low-cost high-resolution fast spin-echo MR of acoustic schwannoma: an alternative
      to enhanced conventional spin-echo MR?
AB  - PURPOSE: To determine whether unenhanced high-resolution T2-weighted fast spin
      echo MR imaging provides an acceptable and less expensive alternative to contrast
      enhanced conventional T1-weighted spin-echo MR techniques in the diagnosis of
      acoustic schwannoma. METHODS: We reviewed in a blinded fashion the records of 25
      patients with pathologically documented acoustic schwannoma and of 25 control
      subjects, all of whom had undergone both enhanced conventional spin-echo MR
      imaging and unenhanced fast spin-echo MR imaging of the cerebellopontine
      angle/internal auditory canal region. The patients were imaged with the use of a
      quadrature head receiver coil for the conventional spin-echo sequences and dual 3
      inch phased-array receiver coils for the fast spin-echo sequences. RESULTS: The
      size of the acoustic schwannomas ranged from 2 to 40 mm in maximum dimension. The
      mean maximum diameter was 12 mm, and 12 neoplasms were less than 10 mm in
      diameter. Acoustic schwannoma was correctly diagnosed on 98% of the fast spin
      echo images and on 100% of the enhanced conventional spin-echo images.
      Statistical analysis of the data using the kappa coefficient demonstrated
      agreement beyond chance between these two imaging techniques for the diagnosis of
      acoustic schwannoma. CONCLUSIONS: There is no statistically significant
      difference in the sensitivity and specificity of unenhanced high-resolution fast
      spin-echo imaging and enhance T1-weighted conventional spin-echo imaging in the
      detection of acoustic schwannoma. We believe that the unenhanced high-resolution
      fast spin-echo technique provides a cost-effective method for the diagnosis of
      acoustic schwannoma.

PMID- 8871701
TI  - T2-weighted MR characteristics of internal auditory canal masses.
AB  - PURPOSE: To determine whether masses of the internal auditory canal are
      hypointense relative to cerebrospinal fluid, and therefore visible, on fast spin
      echo T2-weighted MR images. METHODS: Forty-six patients had 50 masses of the
      internal auditory canal, identified initially on contrast-enhanced MR images,
      that were evaluated retrospectively for signal intensity of the mass with respect
      to cerebrospinal fluid and for visibility of the neural elements within the
      internal auditory canal on T2-weighted images. RESULTS: Forty-seven of 50 masses
      were clearly identified on T2-weighted images. Three small abnormalities (2 to 4
      mm) were not seen with confidence on T2-weighted images. However, on close
      inspection of these three masses, the small abnormality on contrast-enhanced MR
      images corresponded to a hypointense focus on T2-weighted images. All 50 masses
      were hypointense relative to cerebrospinal fluid on T2-weighted images.
      CONCLUSION: All masses of the internal auditory canal in this study were
      hypointense relative to cerebrospinal fluid on T-2 weighted images, and were
      therefore visible.

PMID- 8871702
TI  - Detection of acoustic schwannoma: use of constructive interference in the steady
      state three-dimensional MR.
AB  - PURPOSE: To compare constructive interference in the steady state (CISS) three
      dimensional Fourier transform (3DFT) MR imaging with contrast-enhanced T1
      weighted spin-echo MR imaging for accuracy in detecting acoustic schwannoma.
      METHODS: One hundred twenty-five consecutive patients with possible acoustic
      schwannoma were examined. The accuracy of CISS-3DFT MR imaging in detecting
      abnormalities of the cerebellopontine angle, the internal auditory canal, and the
      inner ear was compared with T1-weighted contrast-enhanced spin-echo MR imaging by
      independent assessment of both image sets by two observers. RESULTS: The
      postcontrast T1-weighted MR images revealed 18 cases of unilateral disease of the
      cerebellopontine angle and/or the internal auditory canal and no case of an
      abnormal bilateral cerebellopontine angle and/or internal auditory canal. Twelve
      cases were pathologically proved acoustic schwannomas. One meningioma of the
      cerebellopontine angle and one metastatic ependymoma to the cerebellopontine
      angle and the internal auditory canal was encountered. The four remaining cases
      had a provisional diagnosis of acoustic schwannoma and were scheduled for follow
      up imaging and clinical review. Analysis of whether contrast material would have
      been administered to the appropriate patients (ie, those with disease of the
      cerebellopontine angle and/or internal auditory canal) according to CISS MR
      imaging findings revealed a sensitivity of 100% and a specificity of 98% for
      observer 1 and a sensitivity of 94% and a specificity of 94% for observer 2.
      CONCLUSION: CISS-3DFT MR imaging, in this patient population, provided high
      sensitivity and specificity in detecting lesions of the cerebellopontine angle
      and internal auditory canal; however, further experience is required before a
      definitive statement regarding the suitability of this technique as a screening
      procedure can be made. When contrast material cannot be administered, CISS MR
      imaging may be considered an adequate examination for the evaluation of possible
      acoustic schwannoma.

PMID- 8871703
TI  - Cost-effective screening for acoustic neuroma with unenhanced MR: a clinician's
      perspective.

PMID- 8871704
TI  - Intensity of MR contrast enhancement does not correspond to clinical and
      electroneurographic findings in acute inflammatory facial nerve palsy.
AB  - PURPOSE: To determine the value of MR contrast enhancement in predicting the
      course of acute inflammatory facial nerve palsy and in selecting patients for
      surgical decompression. METHODS: Six patients with an acute inflammatory
      incomplete or complete peripheral facial nerve palsy (five idiopathic and one
      herpetic in origin) had repeated MR imaging studies with and without contrast
      enhancement, electroneurography, and clinical examinations to establish a
      connection between the intensity of contrast enhancement on MR images, the
      clinical condition, and the electrophysiological data. The examinations were
      performed every second day starting on the first day of admission until clinical
      recovery was proved by clinical deblockage (spontaneous clinical improvement).
      The last examination was performed 3 months after the onset of the facial nerve
      palsy. RESULTS: An abnormal, very intense contrast enhancement of the facial
      nerve was always present in the distal intrameatal and proximal tympanic segments
      and in the geniculate ganglion. The labyrinthine segment exhibited a mild to
      moderate enhancement, and the distal tympanic and mastoid segments showed a
      moderate to intense enhancement. The intensity of contrast enhancement did not
      correspond to the severity, duration, or course of the facial nerve palsy, and
      the electroneurographic data had no predictive value in indicating the severity
      of the inflammatory process. Three months after clinical recovery, a persistent
      and more or less unchanged or even slightly more intense contrast enhancement was
      observed. CONCLUSION: The long-lasting intense contrast enhancement seen in the
      facial nerve segments of patients who have acute peripheral inflammatory facial
      nerve palsy is explained by a two-phase breakdown of the blood-nerve barrier.

PMID- 8871705
TI  - Anatomic Moment. Hearing, I: The cochlea.

PMID- 8871706
TI  - Traumatic luxation of the stapes evidenced by high-resolution CT.
AB  - We encountered a case of acquired perilymphatic fistula in which the origin of
      the disease, namely, the stapes begin medially displaced into the vestibule, was
      shown by thin-section CT. Accordingly, we recommend that every patient with
      suspected perilymphatic fistula of traumatic origin undergo high-resolution CT of
      the petrous bone.

PMID- 8871707
TI  - Clinical assessment of MR of the brain in nonsurgical inpatients.
AB  - PURPOSE: To evaluate the effect of MR imaging of the brain on four domains of
      patient care: diagnosis, diagnostic workup, therapy, and prognosis. METHODS: Pre-
      and post-MR written questionnaires and oral interviews were administered to the
      referring clinicians of 103 medical and neurologic inpatients at a tertiary care
      institution. Additional information was obtained from radiologic reports and
      records. RESULTS: The study population had a diverse array of signs and symptoms
      and of presumptive clinical diagnoses, reflecting the breadth of disease seen at
      our institution. The vast majority of physicians (89%) reported that MR imaging
      added significant diagnostic information, playing an important role in guiding
      diagnostic workup (24%), planning treatment (34%), and estimating prognosis
      (47%). MR imaging was significantly more likely to decrease than to increase
      confidence in the presumptive clinical diagnosis. Thus, MR imaging may be most
      useful in the setting of diagnostic uncertainty. CONCLUSION: Our results show
      that MR imaging of the brain has important effects on each of the four domains of
      care for medical inpatients.

PMID- 8871708
TI  - Assessing the usefulness of diagnostic tests.

PMID- 8871710
TI  - Brain imaging in stroke.

PMID- 8871709
TI  - Utility of repeat brain imaging in stroke.
AB  - PURPOSE: To determine the utility of repeat brain imaging in patients with
      stroke. METHODS: We reviewed the medical records of 98 consecutive patients in
      whom stroke was diagnosed between January 1 and December 31, 1991. We noted the
      number of brain scans performed, the indications cited, and whether repeat
      imaging changed the therapeutic decisions or final diagnosis. RESULTS: Ninety
      eight patients underwent 221 procedures, with 123 repeat imaging studies (98 CT
      scans and 25 MR images). Sixteen patients had only one scan; 51 had two, and 31
      had three or more. Indications for repeat imaging were explicitly documented in
      62 (50%) of 123 repeated scans and inferred in another 41 (33%). In 20 (16%), no
      definite indication could be determined. Indications included lack of acute
      abnormal imaging findings on the initial scan (n = 48, 39%); compliance with
      stroke research protocol (n = 11, 9%). In none of the 82 patients did the
      repeated scan change the diagnosis; therapy was changed in only two (2%) of 82
      patients (aspirin was discontinued). CONCLUSIONS: Repeat imaging in patients
      rarely results in changes in the initial diagnosis or the therapeutic plan;
      indications for repeat imaging are frequently not clearly stated; in certain
      groups of patients with stroke, repeat imaging may not be useful.

PMID- 8871711
TI  - Duplex and color Doppler flow sonography of occlusion and near occlusion of the
      carotid artery.
AB  - PURPOSE: To determine whether color Doppler flow imaging with the use of slow
      flow sensitivity improves sensitivity and specificity in the differentiation of
      occlusion and near occlusion of the internal carotid artery. METHODS: Color
      Doppler and duplex sonography were performed in symptomatic patients who had
      angiographically confirmed occlusion and/or near occlusion of the internal
      carotid artery. The study consisted of two phases: in the first, we assessed the
      usefulness of color Doppler flow imaging by retrospectively reviewing the records
      of 35 patients with 36 angiographically confirmed occlusions or near occlusions
      of the internal carotid artery who were examined with color Doppler flow imaging
      at our institution during a period of 4 years; in the second phase, we
      incorporated color Doppler sonography into the routine scanning protocols of 39
      patients with 41 occluded or nearly occluded internal carotid arteries seen over
      a period of 2 1/2 years. RESULTS: Overall, color Doppler imaging correctly showed
      all 34 of the near occlusions (sensitivity, 100%) and 36 of the 43 occlusions
      (specificity, 84%). Seven patients with angiographically confirmed occlusion had
      sonographic findings that suggested near occlusion. In the first phase, eight
      near occlusions were misinterpreted as occlusions with conventional duplex
      sonography, but were correctly shown with color Doppler flow imaging. In the
      second phase, sensitivity increased from 50% to 100% (18 or 18) because of better
      detection of the nearly occluded lumen. This was at the expense of a decrease in
      specificity (from 100% to 78%). owing to identification of apparent flow in the
      internal carotid artery on color Doppler flow images in five of 23 occlusions.
      CONCLUSION: Because of its ability to depict slow flow, color Doppler imaging
      with slow-flow sensitivity is superior to conventional duplex sonography for the
      noninvasive discrimination of occlusion from near occlusion of the internal
      carotid artery.

PMID- 8871712
TI  - Assessment of brain changes with registered MR before and after bone marrow
      transplantation for chronic myeloid leukemia.
AB  - PURPOSE: To determine the frequency and nature of changes to the brain resulting
      from chemotherapy, radiation therapy, and bone marrow transplantation for chronic
      myeloid leukemia and to compare the sensitivity of conventional and registered MR
      scans for detecting these changes. METHODS: In 15 patients, conventional T1
      weighted, T2-weighted, and fluid-attenuated inversion recovery MR sequences, as
      well as T1-weighted radio frequency spoiled 3-D volume MR scans were performed
      before, 4 to 6 days after, and up to 339 days after transplantation (13
      allografts, two autografts). A subvoxel registration program was used to match
      the volume images precisely so that small changes could be detected after
      subtraction of scans. Five healthy adult control subjects were also studied on
      two occasions 1 month apart. RESULTS: Studies performed 4 to 339 days after
      transplantation showed ventricular enlargement and cortical atrophy in all 13
      patients who had allografts. The changes were evident at 4 to 6 days after
      transplantation and became more obvious during later follow-up examinations.
      Similar changes were seen in one patient with an autograft but no significant
      change was seen in the other patient with an autograft or in the five control
      subjects. Accurately registered volume scans were more sensitive than
      unregistered conventional scans in detecting early (9/10 versus 0/10),
      intermediate (12/13 versus 3/12), and late (10/10 versus 4/9) ventricular
      enlargement on follow-up examinations. The same applied to cortical atrophy (9/10
      versus 0/10, 12/13 versus 0/12, and 10/10 versus 0/9). CONCLUSION: The specific
      cause and clinical significance of these changes are uncertain. Subvoxel
      registration of serial MR images may reveal changes that are poorly seen or not
      apparent on conventional scans.

PMID- 8871713
TI  - Premature aging in persons with Down syndrome: MR findings.
AB  - PURPOSE: To determine whether persons with Down syndrome have features of
      premature aging on routine MR imaging sequences. METHODS: Sixty MR studies (in 30
      persons with Down syndrome and 30 age- and sex-matched control subjects) were
      reviewed retrospectively by two blinded examiners. Sagittal T1-weighted and axial
      T2-weighted spin-echo images were evaluated for the presence and severity of
      three markers of brain aging: atrophy, white matter lesions, and T2 hypointensity
      of the basal ganglia, referenced to the examiner's internal standard of normal
      for that age and sex. RESULTS: Persons with Down syndrome had higher prevalence
      and severity of the three markers studied than the control subjects. Atrophy and
      white matter lesions increased in prevalence with age; abnormal T2 hypointensity
      of the basal ganglia was more equally distributed with age. CONCLUSION: Persons
      with Down syndrome have features of premature aging detectable at routine MR
      imaging.

PMID- 8871714
TI  - Reversible leukoencephalopathy associated with graft-versus-host disease: MR
      findings.
AB  - Ten weeks after undergoing bone marrow transplantation for metastatic lymphoma of
      the parotid gland, a 9-year-old girl became disoriented and had tremor and
      myoclonus in the context of graft-versus-host disease (GVHD). MR images showed
      abnormal signal primarily within the brain stem and deep white matter, which
      resolved almost completely after treatment. The findings are consistent with
      brain involvement by GVHD.

PMID- 8871715
TI  - Reduced caliber of the internal carotid artery: a normal finding with ipsilateral
      absence or hypoplasia of the A1 segment.
AB  - PURPOSE: To determine whether a relationship exists between normal variations in
      anatomy of the circle of Willis and the size of the internal carotid arteries
      (ICA). METHODS: MR angiograms and axial MR images of the brains of 104 patients
      were reviewed. Included were 10 patients with unilateral absence of the A1
      segment of the anterior cerebral artery, 10 with hypoplasia of one A1 segment, 28
      with asymmetric A1 segments, nine with isolated unilateral fetal origin of the
      posterior cerebral artery, and 47 with balanced circulation. RESULTS: The mean
      ICA diameter measurement for the total population was 4.62 +/- 0.68 mm. In
      patients with absent A1, the mean ipsilateral and contralateral ICA diameters
      were 3.63 +/- 0.41 mm and 5.25 +/- 0.52 mm, respectively. The mean percentages of
      the difference between the diameters of the right and left ICA (31% in the group
      with absent A1 and 21% in the group with hypoplastic A1) varied significantly
      from the differences in the ICA diameters among the rest of the population. The
      diameter differences produced by other common variations (unilateral small A1
      segment or fetal origin of the posterior cerebral artery) did not differ
      significantly from those of the 47 patients with balanced intracranial
      circulation. CONCLUSIONS: There is an association of unilaterally absent or
      hypoplastic A1 segments of the anterior cerebral artery with ipsilateral decrease
      in ICA caliber, and this can be seen on MR angiograms.

PMID- 8871716
TI  - MR of the cerebral operculum: abnormal opercular formation in infants and
      children.
AB  - PURPOSE: To evaluate abnormalities of the cerebral operculum in infants and
      children and to propose the embryogenic basis of abnormal opercular formation as
      determined from MR imaging findings. METHODS: Eighty-six infants and children who
      had abnormally wide interopercular distances and/or distorted opercular
      topography seen on MR images were studied retrospectively. Clinically, patients
      presented with tonal abnormalities, macrocephaly, microcephaly, seizures,
      developmental delay, cerebral palsy, or facial dysmorphism. The abnormal opercula
      were compared with developing opercula at different stages of gestation. RESULTS:
      Among the 86 infants and children, two categories of opercular abnormalities were
      identified: an underdeveloped operculum (n = 64) and a malformed operculum (n =
      22). The malformed operculum was further classified into three subtypes:
      nonformation of the operculum with lissencephaly (n = 1, 1%), abnormal opercular
      formation with pachygyria (n = 11, 13%), and nonformation or abnormal formation
      of the operculum without pachygyria or lissencephaly (n = 10, 12%). Two subtypes
      of the underdeveloped operculum were identified: an open operculum without a
      normal insula (n = 6, 7%) and an open operculum with a normal insula (n = 58,
      67%). The five subtypes of abnormal opercular configuration showed a range of
      maturity that was comparable to the developing operculum at different ages.
      CONCLUSION: Opercular anomalies appear to follow sequentially predetermined
      normal steps in development. Arrest in opercular development or malformation may
      occur after an initial insult. MR imaging is the method of choice by which to
      identify these abnormalities.

PMID- 8871717
TI  - Congenital arhinia.
AB  - In a case of congenital absence of the nose, spiral axial CT showed a tiny
      piriform anterior aperture on the right that ended blindly. Three-dimensional
      reformation of CT data showed an atretic bony plate, blind-ending right nostril,
      absent nasal bones, and inferior continuation of the metopic suture. Noncontrast
      MR findings in the brain were normal.

PMID- 8871718
TI  - Subcortical heterotopia: a distinct clinicoradiologic entity.
AB  - PURPOSE: To investigate the clinical syndrome and associated brain anomalies in a
      group of patients with subcortical heterotopia. METHODS: The seizure history,
      developmental history, family history, electroencephalographic results, imaging
      studies, and pathologic results (where available) of 13 patients with subcortical
      heterotopia were reviewed retrospectively. The patients ranged in age from 1
      month to 39 years (mean, 11 years; median, 3 years) at the time of the most
      recent update of their records. RESULTS: Fifteen hemispheres were involved in 13
      patients. The cerebral cortex overlying the heterotopia was thin with shallow
      sulci and the affected part of the hemisphere was small as compared with the
      contralateral hemisphere. The corpus callosum was hypogenetic or agenetic in nine
      patients and the basal nuclei were dysplastic or hypoplastic in 11 patients. Most
      patients were developmentally delayed as children, had mild hemiplegia or
      hemihypesthesia contralateral to the affected hemisphere(s), and had partial
      epilepsy, most commonly evidenced by partial motor seizures in the body half
      contralateral to the malformation. Age at seizure onset varied from infancy to
      the second decade. Electroencephalographic results showed slow wave background
      with spike and spike wave complexes in the affected hemisphere. CONCLUSION:
      Subcortical heterotopia seems to have characteristic clinical,
      electrophysiological, and imaging manifestations. These results suggest that
      affected patients may be conveniently grouped together to study treatment
      outcomes.

PMID- 8871719
TI  - Repermeation of partially embolized cerebral arteriovenous malformations: a
      clinical, radiologic, and histologic study.
AB  - PURPOSE: To describe the pattern and time course of embolization-related tissue
      lesions and repermeation of the intranidal cast after endovascular embolization
      of cerebral arteriovenous malformations (AVMs) with N-butyl cyanoacrylate (NBCA).
      METHODS: We retrospectively reviewed the records of 26 patients who were treated
      by endovascular embolization with NBCA and subsequent surgical extirpation to
      look for embolization-related tissue lesions and repermeation of the cast. A
      residual flow through the malformation was identified on preoperative angiograms
      in every case. RESULTS: Pattern and time course of embolization-related tissue
      lesions were typical. Until 3 months after embolization, repermeation of
      embolized structures did not occur. In contrast, repermeation was found in every
      patient who had surgery later than 3 months after the first embolization (n = 13;
      50%). In these cases, histologic examination of the resected nidus disclosed
      capillary structures inside the lumen of embolized vessels. Capillaries were
      traced immunohistochemically with antibodies against membrane-bound factor VIII.
      No parameter other than the interval between the first embolization and surgery
      was found to relate to the repermeation of the cast. CONCLUSION: Intranidal
      recapillarization can occur later than 3 months after the first embolization with
      NBCA if total and solid casting of the nidus was not accomplished.

PMID- 8871720
TI  - Intraaneurysmal flow: evaluation with Doppler guidewires.
AB  - Flow dynamics in cerebral aneurysms were studied with the use of Doppler
      guidewires in two patients. In both cases it was possible to reach the aneurysmal
      sac and to assess intraaneurysmal flow. Torquability and flexibility of the new
      Doppler guidewires permitted continuous assessment of flow velocity and flow
      pattern at the dome as well as in the neck area. Flow velocities were higher at
      the neck than within the aneurysmal sac (88 cm/s > 28 cm/s). Because of the
      limited area of interrogation (sample volume, 5 mm) it was not possible to
      investigate the complete intraaneurysmal space.

PMID- 8871721
TI  - Endovascular therapeutic approach to peripheral aneurysms of the superior
      cerebellar artery.
AB  - Peripheral aneurysms of the superior cerebellar artery may be difficult to treat
      surgically owing to their inaccessibility and to the frequent inability to
      preserve the involved parent artery. In fact, for most cases, surgical treatment
      consists of proximal parent artery occlusion and/or trapping with surgical clips.
      An equivalent endovascular therapeutic approach to these lesions may be an
      attractive alternative method of management. We describe two cases of peripheral
      superior cerebellar artery aneurysms that were treated successfully with
      endovascular embolization.

PMID- 8871722
TI  - Clinical use of mechanical detachable coils for dural arteriovenous fistula.
AB  - Seven dural arteriovenous fistulas were successfully embolized with mechanical
      detachable coils. Two lesions were located in the transverse-sigmoid sinus, four
      in the cavernous sinus, and one in the marginal sinus. All lesions were
      completely occluded on postembolization angiography. No recurrent symptoms
      appeared during a mean follow-up period of 11 months. Owing to the length and
      retrievability of the mechanical detachable coils, embolization was quicker and
      safer, and coils were packed more densely, than is possible with conventional
      coils. Coil migration was avoided because coils of the appropriate size were
      chosen before they were placed.

PMID- 8871723
TI  - MR characteristics of primary extramedullary plasmacytoma in the head and neck.
AB  - PURPOSE: To define MR characteristics of primary extramedullary plasmacytoma in
      the head and neck using a variety of plain and contrast-enhanced MR protocols.
      METHODS: Six patients with primary extramedullary plasmacytoma in the head and
      neck were examined clinically and with MR imaging at 1.5 T. The morphologic
      appearance and signal intensities of the lesions were analyzed and the results of
      the imaging findings were compared with histopathologic findings. RESULTS:
      Qualitative analysis showed that five lesions were oval and sharply demarcated
      without signs of infiltration; the other lesion filled the parapharyngeal space
      bilaterally. On t2-weighted sequences, the lesions had moderate signal intensity.
      On plain T1-weighted sequences, the tumors were isointense or slightly
      hyperintense with respect to surrounding muscles; after administration of
      contrast medium, four lesions notable enhancement, with distinct central
      inhomogeneity. CONCLUSION: Although morphologic features or evidence of contrast
      enhancement do not assure certain diagnosis of extramedullary plasmacytoma, these
      MR imaging characteristics should prompt the radiologist to include this rare
      lesion in the differential diagnosis.

PMID- 8871724
TI  - CT in adult supraglottitis.
AB  - We describe the CT appearance of supraglottitis and its complications in three
      adults. The most common CT findings were thickening of the epiglottis,
      aryepiglottic folds, false and true vocal cords, obliteration of the
      preepiglottic fa, thickening of the platysma muscle, and reticulation of the
      subcutaneous fat. Multiple loculated fluid-density collections consistent with
      abscesses were seen in one patient. Although the diagnosis of supraglottitis is
      generally made on the basis of the patient's history and by direct endoscopy, CT
      may be used to confirm the diagnosis when an adequate laryngoscopic examination
      cannot be performed. CT is also useful in evaluating the complications of this
      disorder.

PMID- 8871725
TI  - Percutaneous CT-guided aspiration of deep neck abscesses.
AB  - Four patients with deep neck or retropharyngeal abscesses underwent CT-guided
      aspiration and drainage from either of two percutaneous approaches. Percutaneous
      drainage contributed to prompt and/or dramatic clinical responses in all four
      patients by effecting decompression of the abscess cavities and by improving the
      ability to assess infectious organisms. There were no complications in this small
      group. Precutaneous drainage obviated more traditional invasive surgery.

PMID- 8871726
TI  - Intracranial hemangiopericytomas: MR and CT features.
AB  - PURPOSE: To describe the MR and CT imaging features of hemangiopericytoma and to
      identify the characteristics that might distinguish them from meningioma.
      METHODS: We retrospectively reviewed the CT and MR findings in 34 pathologically
      proved cases of hemangiopericytoma. We evaluated the size, shape, and location of
      the tumor; the presence of hydrocephalus, edema, and mass effect; the type of
      dural attachment (broad-based or narrow-based) and bone changes (erosion,
      hyperostosis); and the tumor's density, signal, and contrast-enhancement
      characteristics. RESULTS: Thirty of 34 tumors were 4 cm or more in greatest
      dimension, 32 were lobular, and only seven were in the posterior fossa.
      Hydrocephalus was present in 18, edema in 30, and mass effect in 33. Twenty-three
      had broad-based dural attachment and 11 had narrow-based attachment. All 26
      unenhanced CT scans showed hyperdense tumors; 19 were heterogeneous and seven
      homogeneous. All 27 contrast-enhanced CT scans showed enhancement; 17 were
      heterogeneous and 10 homogeneous. Bone erosion was present in 17 of 29
      hemangiopericytomas imaged with CT. None had hyperostosis or tumor
      calcifications. On T1-weighted MR images, 13 of 17 tumors were isointense with
      cortical gray matter; on T2-weighted image, 10 of 17 were isointense. All 14
      tumors imaged with contrast enhanced T1-weighted MR imaging showed enhancement,
      and 13 of these were heterogeneous; eight of the 14 had a "dural tail" sign.
      CONCLUSION: Intracranial hemangiopericytomas are multilobulated, extraaxial
      tumors, sometimes associated with narrow-based dural attachment and bone erosion.
      Unlike with meningiomas, hyperostosis and intratumoral calcification are not
      present.

PMID- 8871727
TI  - Spinal subdural enhancement after suboccipital craniectomy.
AB  - PURPOSE: To characterize transient intraspinal subdural enhancement (potentially
      mimicking the subarachnoid spread of tumor) seen on MR images in some children
      after suboccipital craniectomy for posterior fossa tumor resection. METHODS:
      Radiologic and medical records of 10 consecutive children who had MR imaging for
      spinal staging after resection of posterior fossa tumor during a 9-month period
      were reviewed retrospectively. In addition, one case with similar findings of
      intraspinal enhancement on spinal staging MR images obtained at another
      institution was included in the review. RESULTS: Intraspinal enhancement thought
      to be subdural was seen in four of 10 patients undergoing spinal staging MR
      imaging 6 to 12 days after surgery. In these four patients, MR studies 50 to 18
      days later, without intervening treatment, showed resolution of the abnormal
      enhancement. A fifth patient (from another institution) with similar intraspinal
      enhancement underwent CT myelography 4 days later, which showed no subarachnoid
      lesions. No metastases have developed in any of these five patients during the
      2.5- to 3.5-year follow-up period. conclusions: From analysis of the MR
      appearance and on the basis of prior myelographic experience, we suggest an
      extraarachnoid, probably subdural, location of this enhancement. Awareness of
      this phenomenon will reduce the rate of false-positive diagnoses of metastatic
      disease. Preoperative spinal staging should be considered for patients undergoing
      suboccipital craniectomy.

PMID- 8871728
TI  - MR signal intensity of the optic radiation.
AB  - PURPOSE: To determine whether a hyperintense layer adjacent to the lateral
      ventricle on T2-weighted MR images represents the optic radiation. METHODS: We
      reviewed 11 brain specimens from patients with nonneurologic diseases and MR
      images from 43 healthy volunteers. The MR images in a patient with cerebral
      infarction involving the lateral geniculate body were also reviewed to evaluate
      wallerian degeneration of the optic radiation. RESULTS: The external sagittal
      stratum, composed of the optic radiation, showed a pale layer in specimens
      stained by Bodian's method. On high-power microscopic views of the specimens, the
      axons of the external sagittal stratum were large and separated by wide
      translucent spaces. In the volunteers, the external sagittal stratum appeared
      hyperintense on T2-weighted MR images and hypointense on T1-weighted images. The
      MR images in a patient with cerebral infarction showed hyperintensity within the
      layer corresponding to the external sagittal stratum. CONCLUSIONS: The
      hyperintense layer on T2-weighted images represents the external sagittal
      stratum, or optic radiation. The signal intensity of the external sagittal
      stratum reflects histologic characteristics of low axonal density.

PMID- 8871729
TI  - Hypervascular tumor of the buccal space in an adult as a late recurrence of
      juvenile angiofibroma.
AB  - We describe an adult patient with recurrent juvenile angiofibroma, which
      presented as a rapidly enlarging, hypervascular mass in the anterior part of the
      cheek. The case is unusual because of the extreme delay (greater than 30 years)
      and the anatomic location of the recurrence.

PMID- 8871730
TI  - Ki- 1-positive anaplastic large cell lymphoma of the masticator space with
      intracranial extension.
AB  - Ki- 1-positive anaplastic large cell lymphoma (ki- 1 ALCL) is a recently
      recognized form of non-Hodgkin lymphoma occurring predominantly in the skin
      and/or peripheral lymph nodes. We report the clinical, pathologic, and
      radiographic findings of a case of Ki- 1 ALCL arising within the masticator space
      and extending intracranially into the epidural space.

PMID- 8871731
TI  - The role of imaging in the diagnosis of giant cell tumor of the skull base.
AB  - An expansile temporal bone lesion above the temporomandibular joint (TMJ) in a 55
      year-old woman was initially diagnosed as pigmented villonodular tenosynovitis.
      Preoperative embolization of the tumor had resulted in excessive tumoral
      hemorrhagic pigment. The surgical and CT findings suggested that the TMJ was not
      involved, and a final diagnosis of giant cell tumor was made.

PMID- 8871732
TI  - Choroid plexitis caused by cytomegalovirus in a patient with AIDS.

PMID- 8871733
TI  - Annotated bibliography.

PMID- 8871734
TI  - Cytokines and allergic rhinitis.
AB  - Cytokines that are important in the pathophysiology of allergic diseases are
      summarized in Table II. The role of certain of these cytokines, especially IL-4
      as well as IL-1, IL-2, IL-6, GM-CSF, and TNF-alpha have been documented in nasal
      biopsies and/or nasal secretions of patients with allergic rhinitis. The
      improvement of symptoms of allergen rhinitis induced by corticosteroid therapy or
      immunotherapy were associated with differences in cytokine expression, whereas,
      steroids decreased IL-4 expression and immunotherapy increased expression of IL-2
      and IFN-gamma. These data indicate that these proven therapies most probably are
      mediated by different mechanisms with different cytokine expression.

PMID- 8871735
TI  - Nasal physiology: neurochemical receptors, nasal cycle, and ciliary action.
AB  - The complex interaction of neurotransmitters, vascular supply, and mucociliary
      function constitute one of the main defense mechanisms of the respiratory tract,
      modulating airflow and response to noxious assault. One of the main controls of
      airflow relies upon the modulation of vasodilation and vasoconstriction via the
      autonomic control of a sinusoid system. In addition to noradrenaline and
      acetylcholine, an ever-increasing number of neurotransmitters are involved,
      including neuropeptide Y, vasoactive intestinal peptide, peptide histidine
      leucine, substance P, and calcitonin gene-related peptide. The existence of a
      reciprocating cycle of congestion and decongestion has been recognized for over a
      century, although its exact function is unknown. Recent studies using acoustic
      rhinometry have demonstrated that the cycle is present in some form in the
      majority of adults, in children as young as 3 years, and that it persists after
      cessation of nasal airflow. It may, however, be overridden or modulated by many
      environmental and pathological situations. By contrast, the defense function of
      mucociliary clearance is well-established, and while also subject to
      environmental influences, relies upon an innate and cyclical pattern of mucus
      flow from within the sinuses and nasal cavity into the oropharynx. The content of
      the mucus is fundamental to its protective function and the control of
      mucociliary clearance intimately related to autonomic activity.

PMID- 8871736
TI  - Learning impairment and allergic rhinitis.
AB  - Allergic rhinitis is underestimated as a cause of suffering and diminished
      quality of life in children and adolescents. If nasal symptoms such as itching,
      sneezing, rhinorrhea, and congestion are not well controlled during the day, they
      may contribute to learning problems during school hours. If these symptoms are
      not well controlled during the night, they may contribute to nocturnal sleep
      loss, secondary daytime fatigue and learning impairment. Even uncomplicated
      seasonal allergic rhinitis may be associated with reduced ability to learn, and
      the likelihood of learning problems may increase in severe perennial rhinitis or
      in rhinitis associated with complications such as sinusitis or eustachian tube
      dysfunction and conductive hearing loss. Also, many of the medications used to
      treat allergic rhinitis may cause central nervous system adverse effects and
      contribute to learning impairment. For some medications, such as inhaled
      glucocorticoids and decongestants, the potential effect on central nervous system
      function and learning has not been tested. For others such as H1-receptor
      antagonists (antihistamines), well-designed, prospective studies have been
      performed. The newer relatively nonsedating medications such as terfenadine,
      astemizole, loratadine, cetirizine, and fexofenadine have less potential to
      impair central nervous system function and learning than their predecessors.

PMID- 8871738
TI  - Asthma and rhinitis in wooding workers.
AB  - We present some cases of rhinitis and asthma in wooding workers exposed to hard
      or soft woods. The specific provocation test confirmed the diagnosis of rhinitis
      in three patients and of asthma in four. Rhinitis was caused by oak, beech, and
      pine, while asthma was caused by obeche, chestnut, acacia, and iroko.
      Occupational exposure to the specific wood, before onset of symptoms (symptom
      latency) was shorter for patients with asthma. All seven patients with
      respiratory symptoms were nonsmokers; three were atopics and four, all with
      asthma, had nonspecific bronchial hyperreactivity. Twenty-four hours after the
      test, PD20FEV1 had decreased in two cases with rhinitis and two with asthma,
      although the data did not reach statistical significance (Wilcoxon matched-pairs
      test: NS). After the SBPT, blood eosinophils increased in two cases with rhinitis
      and three with asthma, and the data were at the limit of statistical significance
      (P = 0.046). The study confirms that not only hard essences, but also soft woods
      can cause respiratory symptoms, although the pathogenetic mechanisms are still
      unclear. A specific provocation test is still the best and sometimes only means
      of diagnosing wood asthma; standardized protocols with repeated measurements of
      nonspecific airway responsiveness and of eosinophils in the blood may be helpful
      for a better understanding of the pathogenetic mechanism and predisposing
      factors.

PMID- 8871737
TI  - Serum ECP levels in asthmatic patients: comparison with other follow-up
      parameters.
AB  - In recent years, eosinophil cationic protein (ECP) has been considered as a
      useful eosinophilic activation marker in asthmatic patients. In this study, serum
      ECP levels in different stages of bronchial asthma were evaluated. We studied 123
      patients suffering from asthma, which was classified as mild (n = 49), moderate
      (n = 49), severe asthma (n = 25), and also 31 healthy controls. Serum ECP levels
      were 13.22 +/- 1.11 ng/mL (mean +/- s.e.m.) in controls, and 30.15 +/- 2.38 ng/mL
      in asthmatic patients. By subgroups, ECP levels were 24.23 +/- 3.37 ng/mL, 31.69
      +/- 4.21 ng/mL and 37.61 +/- 4.52 ng/mL, in mild, moderate and severe asthmatic
      patients, respectively, being the differences among the three groups
      statistically significant (P < 0.01-P < 0.001). Peripheral blood eosinophil
      numbers were 157 +/- 20 eos/mm3 in controls, and 334 +/- 35 eos/mm3, 510 +/- 87
      eos/mm3, and 658 +/- 72 eos/mm3, in mild, moderate, and severe asthmatic
      patients, respectively, with significant differences among all groups (P < 0.05-P
      < 0.001). The serum ECP levels as well as the eosinophil numbers were higher in
      symptomatic patients than in the asymptomatic ones (P < 0.01). Moderate negative
      correlations, although highly significant (P < or = 0.001), were found between
      serum ECP levels and forced vital capacity (FVC) (rs = -0.27), FEV1, MEF25-75 (rs
      = -031), and MEF50 (rs = -0.32). There was also a good positive correlation
      between ECP levels and peripheral blood eosinophil numbers (rs = 0.67, P <
      0.001).

PMID- 8871739
TI  - Severe reactions to cow's milk in very young infants at risk of atopy.
AB  - Cow's milk (CM) allergy (CMA) is a disease of infancy, usually appearing in the
      first months of life. Symptoms triggered by CM at first introduction are not
      completely defined. The aim of this study was to investigate the prevalence of
      severe reaction to CM and clinical manifestation triggered by CM administration
      in the first few months of life. Particularly sensitizing appears to be the
      exposure to CM formulas in the neonatal nursery. The little doses of allergens
      are more sensitizing than larger ones. These data provide clear evidence of the
      immunological effects of oral antigen administration during the neonatal period.
      Babies at risk of atopy should receive in their first days colostrum and/or
      formulas appropriate for atopy prevention. In this prospective study, we
      evaluated 27 babies in order to ascertain the prevalence of CM-induced severe
      reactions.

PMID- 8871741
TI  - Anaphylaxis to the ingestion and inhalation of Tenebrio molitor (mealworm) and
      Zophobas morio (superworm).
AB  - It has been well documented, worldwide, that inhalation and/or contact with
      airborne particulate insect products has resulted in sensitivity to insect
      proteins and is manifested by such common entities as dermatitis, conjunctivitis,
      rhinitis, and asthma. However, the deliberate ingestion of a variety of insects
      (undertaken to prove their edibility and nutrient value) resulted in subsequent
      sensitization of some individuals. Such an outcome has not previously been
      reported in the literature. The objective was to document the anaphylactic
      reaction to the purposeful ingestion of mealworm in an individual known to be
      sensitized to the inhalation of beetle larvae. We used the occasion of the
      Centennial Celebration of The New York Entomological Society to expose members
      and guests of the Society to the ingestion of various insects. The subjects of
      the study consisted of: 1) Three members were adversely affected; 2) One
      individual with Baker's asthma; and 3) A number of controls with no known
      hypersensitivity to insect products. The investigation was undertaken by food
      challenges, inhalation challenges, skin testing to the individual insect
      allergens, a) Tenebrio molitor (TM), b) Zophobas morio (ZM), c) Blattella
      germanica (BG), skin testing to common indoors and outdoor allergens, and direct
      bind ELISA and ELISA inhibition. One individual manifesting hypersensitivity both
      by ingestion and inhalation to mealworm was identified. This sensitivity was
      documented clinically as well as by objective testing.

PMID- 8871740
TI  - Purified natural rubber latex antigens show variable reactivity with IgE in the
      sera of latex allergic patients.
AB  - Immediate-hypersensitivity reactions related to latex products have increased
      rapidly in recent years. However, a reliable diagnosis is hampered by lack of
      purified and well characterized latex allergens. We have purified allergens in
      natural rubber latex (NRL) after SDS-PAGE by electroelution, and tested specific
      IgE-binding activities of these isolated allergens by ELISA. Ten sera from spina
      bifida patients and 5 sera from health care workers with latex allergy were
      evaluated for specific IgE antibody in the sera using ELISA. Five normal controls
      with no evidence of latex allergy were also studied. None of the isolated
      allergens reacted with normal control sera used. Among the latex allergic
      patients' sera studied, 11, 9, 9, 2, and 6 sera reacted with 27, 23, 21, 17, and
      10 kDa isolated allergens, respectively. Each latex allergic serum reacted with
      at least one of the purified allergens, indicating a diversity in response to
      latex. The isolated and purified latex allergens may, however, be useful to
      identify latex allergy in patients.

PMID- 8871742
TI  - John Paul Jones (1747-1792), American Naval Officer.

PMID- 8871743
TI  - William IV (1765-1837), King of Great Britain, Ireland and Hanover.

PMID- 8871744
TI  - Ludwig van Beethoven (1770-1827), German composer.

PMID- 8871745
TI  - The effect of managed care on orthopedic education.

PMID- 8871746
TI  - Femoral nerve palsy after arthroscopic surgery with an infusion pump irrigation
      system.

PMID- 8871747
TI  - Ganglion of the anterior cruciate ligament presented as a knee mass.

PMID- 8871748
TI  - Biologic markers of arthritis.

PMID- 8871749
TI  - Extraction of femoral nails. Can we build a better mousetrap?

PMID- 8871750
TI  - Proximal interphalangeal joint injuries of the hand. Part II: Treatment and
      complications.
AB  - This is the second of a two-part series reviewing injuries to the proximal
      interphalangeal (PIP) joint of the hand. In part one, we reviewed the normal
      anatomy, classification, diagnosis, and pathoanatomy of the various injuries. In
      this article, we focus on the treatment options and complications associated with
      each of the injury types. Aggressive, early range of motion in a supervised
      therapy program is emphasized as the mainstay of treatment.

PMID- 8871751
TI  - Baseline hemoglobin as a predictor of risk of transfusion and response to Epoetin
      alfa in orthopedic surgery patients.
AB  - A multicenter, double-blind, placebo-controlled, parallel-group study was
      undertaken to determine whether Epoetin alfa can reduce perioperative transfusion
      requirements. Twenty-six medical centers enrolled 316 patients who were scheduled
      for major orthopedic surgery and were expected to require > or = 2 units of
      blood. Patients were stratified according to baseline hemoglobin levels and
      randomly assigned to receive either Epoetin alfa (300 IU/kg or 100 IU/kg) or
      placebo for 15 consecutive days starting 10 days prior to, on the day of, and for
      4 days after surgery. Epoetin alfa (300 IU/kg) resulted in significantly less
      exposure to allogeneic blood transfusion compared with placebo (16%) versus 45%)
      in patients whose baseline hemoglobin level was > 10 to < or = 13 g/dL (P =
      0.024). Mean number of units transfused per patient was also lower among those
      treated with Epoetin alfa (overall, P = 0.027). Epoetin alfa was safe and well
      tolerated in this population.

PMID- 8871752
TI  - A safety and efficacy comparison study of two dosing regimens of epoetin alfa in
      patients undergoing major orthopedic surgery.
AB  - Previous studies have demonstrated the efficacy of perioperative Epoetin alfa in
      decreasing allogeneic transfusion exposure in patients undergoing orthopedic
      surgery. A randomized, multicenter trial was conducted comparing the safety and
      efficacy of a weekly Epoetin alfa dosing regimen in patients with hemoglobin
      levels > or = 10 to < or = 13 g/dL scheduled to undergo major elective orthopedic
      arthroplasty, with a daily regimen previously shown to be effective. patients on
      the weekly regimen showed a greater baseline-to-presurgery hemoglobin increase
      versus the daily regimen group (1.44 +/- 1.029 g/dL versus 0.73 +/- 0.867 g/dL).
      Moreover, the weekly 600 IU/kg regimen was similar to the daily 300 IU/kg regimen
      with respect to safety and the avoidance of allogeneic transfusion. These data
      showed the weekly Epoetin alfa regimen to be at least as efficacious as the daily
      regimen and more convenient.

PMID- 8871753
TI  - Biomechanics of rigid tibial nail insertion sites.
AB  - The use of a very proximal insertion site for rigid intramedullary nailing was
      evaluated in a biomechanical study. The purpose of this study was to compare the
      bursting strains generated in a proximal tibia fracture fragment during rigid
      nailing, using the recommended insertion sites versus a more proximal site just
      anterior to the tibial plateau in the midline. Proximal one-third tibia fractures
      were created in 12 pairs of fresh cadaver specimens. Strain gauges were applied
      to the medial and lateral cortices of the proximal fragments. Lottes nails,
      Grosse-Kempf nails, and unreamed Russell-Taylor nails were inserted in four
      successive pairs of specimens. In each pair, one side used the recommended
      starting point, and the other side used the proximal insertion site. The strain
      was recorded at successive 2- to 4-cm depth intervals during nail insertion. In
      the Lottes group, much larger bursting strains were generated in the lateral
      cortex when using a distal starting point (P < 0.05). In the unreamed Russell
      Taylor group, the anteromedial surface strains were significantly increased using
      a distal starting point (P < 0.05). The Grosse-Kempf group showed no significant
      difference in strains associated with any insertion point during tibial
      intramedullary nailing.

PMID- 8871754
TI  - Heterotopic ossification following total knee arthroplasty requiring surgical
      excision.
AB  - We present a case of progressive heterotopic ossification (HO) after cementless
      total knee arthroplasty causing painful stiffness that was treated with surgical
      excision. The patient had few risk factors associated with HO, including minimal
      anterior notching and dissection of the distal femoral cortex. The patient did
      undergo manipulation; however, this occurred after the diagnosis of HO was made.
      This report documents a rare case of HO following total knee arthroplasty that
      required surgical excision.

PMID- 8871755
TI  - Pectoralis tendon avulsion in the skeletally immature.
AB  - Pectoralis tendon avulsion is a rare injury typically occurring in skeletally
      mature men. The diagnosis can be difficult to make and is often delayed. We
      report a case of a complete bony avulsion of the pectoralis tendon at the site of
      its humeral insertion in a skeletally immature male. The palpable and
      radiographic evidence of ossification at the injury site made the diagnosis in
      this adolescent case uniquely obvious.

PMID- 8871756
TI  - Diagnosis and treatment of posterior sternoclavicular joint dislocations in
      children.
AB  - Posterior dislocation of the sternoclavicular joint is uncommon in children,
      difficult to diagnose, and may be confused with a physical injury of the medial
      clavicle. We reviewed our experience with posterior dislocations of the medial
      clavicle over a 10-year period, and found 5 children who had sustained this
      injury. The computed tomography (CT) scan was found to be the best diagnostic
      procedure to assess the integrity of the sternoclavicular joint. The cause of the
      dislocation was most commonly lateral compression of the shoulders sustained
      during contact sports, particularly football and hockey. Reduction was usually
      obtained by retraction of the shoulders; for persistent dislocations, a towel
      clip was used to lift the medial end of the clavicle into its reduced position
      with the patient under general anesthesia. Reduction was maintained with a figure
      of-eight bandage. Any child presenting with pain and swelling in the region of
      the sternoclavicular joint and no evidence of obvious fracture of the clavicle
      should have the possibility of dislocation of the sternoclavicular joint
      investigated with a CT scan.

PMID- 8871757
TI  - The effect of soluble complement receptor 1 (sCR1) and human thyroid antibodies
      on the course of experimental autoimmune thyroiditis in rats.
AB  - Experimental autoimmune thyroiditis (EAT), induced by immunisation of rats with
      thyroid extract and complete Freund's adjuvant, has been used as a model to study
      the effects of complement inhibition mediated by soluble complement receptor 1
      (sCR1) administration during the initial phase of the disease. There was no
      effect of sCR1 on the severity of thyroiditis at day 28 after immunisation or on
      the levels of thyroid antibodies, whether sCR1 was given during the first or
      second week after immunisation. Human IgG containing high levels of thyroid
      peroxidase antibodies given to rats at the time of immunisation caused
      significant worsening of thyroiditis severity (P < 0.01 compared to animals
      receiving normal IgG) but sCR1 again had no effect in this variant of the EAT
      model. The results indicate that complement does not play a major role in the
      initial phase of tissue injury in EAT and complement inhibition does not impair
      the generation of an autoimmune response against the thyroid, although it remains
      possible that complement activation is important during the chronic phase of
      disease maintenance in human autoimmune thyroid disease.

PMID- 8871758
TI  - The role of alpha 4 integrin and intercellular adhesion molecule-1 (ICAM-1) in
      murine experimental autoimmune thyroiditis.
AB  - Mouse-thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg
      induce a lymphocytic form of experimental autoimmune thyroiditis (EAT) whereas
      activation of the same cell population with MTg in the presence of anti
      interleukin 2 receptor antibody (M7/20) induces a granulomatous form of EAT. The
      thyroid infiltrate in both lymphocytic and granulomatous EAT includes both CD4+
      and CD8+ T cells and CD4+ T cells are the primary effector cells for both forms
      of EAT. This investigation was undertaken to begin to define the roles of alpha 4
      integrin, and intercellular adhesion molecule-1 (ICAM-1) in the migration of CD4+
      and CD8+ T cells to the thyroid in EAT. The studies presented here demonstrate
      the expression of alpha 4 integrin and ICAM-1 on CD4+ and CD8+ T cells
      infiltrating the thyroid and the expression of vascular cell adhesion molecule
      (VCAM) and ICAM-1 on thyroid cells of mice with EAT. The effects of anti-alpha 4
      and anti-ICAM mAb administration on EAT severity in recipient mice was also
      determined. Anti-alpha 4 administration reduced or abolished lymphocyte
      infiltration in the thyroid resulting in reduced severity of both lymphocytic and
      granulomatous EAT. In contrast, anti-ICAM mAb had little effect on EAT severity.
      These results suggest that these two adhesion molecules exhibit differential
      functional roles in the modulation of EAT disease severity and that alpha 4-VCAM
      interactions may be of particular importance in trafficking of effector cells to
      the thyroid.

PMID- 8871759
TI  - Peripheral blood in Sjogren's syndrome does not contain increased levels of T
      lymphocytes reactive with the recombinant Ro/SS-A 52 kD and La/SS-B 48 kD
      autoantigens.
AB  - Patients with Sjogren's syndrome (SS) frequently have anti-Ro/SS-A and anti-La/SS
      B autoantibodies. The aim of this study was to investigate if these patients have
      peripheral blood lymphocytes (PBL) secreting IFN-gamma after short-term
      cultivation in the presence of Ro/SS-A and La/SS-B antigens. The frequency of PBL
      secreting IFN-gamma was examined in 12 SS patients and 11 healthy controls. The
      enzyme-linked immunospot (ELISPOT) assay was performed after 48 hours cultivation
      of PBL in the presence of recombinant Ro 52 kD protein or recombinant La 48 kD
      protein. The number of unstimulated IFN-gamma secreting cells in the SS patient
      group was not significantly different from that of the control group. Moreover,
      no increase in the number of IFN-gamma secreting cells after Ro/SS-A and La/SS-B
      stimulation was detected in the two groups. Thus, T cells reactive with the
      recombinant Ro 52 kD and La 48 kD proteins do not occur with any increased
      frequency in peripheral blood of SS patients.

PMID- 8871760
TI  - The pathogenicity of spontaneously-occurring thyroglobulin-reactive T lymphocytes
      from BB/WOR rats.
AB  - Autoantigen-reactive T lymphocytes have been implicated in the pathogenesis organ
      specific autoimmune disease. Thyroglobulin (Tg) is one of the primary
      autoantigens associated with autoimmune lymphocytic thyroiditis (LT). These
      experiments investigated the pathogenicity of a lymphocyte line derived from
      spontaneously-occurring Tg-reactive T lymphocytes isolated from unprimed NB line
      BB/Wor rats which have nearly a 100% incidence of spontaneous LT. Adoptive
      transfer of LT was accomplished by injecting 1.0 x 10(5) Tg-reactive lymphocytes
      into the tail vein of MHC compatible, non LT-prone BB line BB/Wor rats. All of
      the Tg-reactive cell line recipients (5/5) developed LT compared to only 20%
      (1/5) of the control rats given a parallel tetanus toxoid-reactive T cell line (p
      < 0.05, Fisher's exact test). Furthermore, despite the presence of LT, only one
      Tg-reactive cell line recipient developed insulitis. When Tg-reactive lymphocytes
      were incubated with an MHC compatible Wistar rat thyrocyte line at increasing
      effector: target ratios, the T cell line lysed thyrocytes in a dose-response
      fashion (r = 0.99, p < 0.05, linear regression), but did not lyse smooth muscle
      cell targets. FACS analysis established that this cell line is CD8 predominant.
      This is the first study to demonstrate that spontaneously-occurring Tg-reactive T
      lymphocytes from a nonimmunized animal model for LT are pathogenic. Further
      investigations into the repertoire of Tg-reactive lymphocytes in BB/Wor rats
      should provide insight into the pathogenesis of autoimmune thyroid disease and
      provide a basis for targeted immunotherapy.

PMID- 8871761
TI  - Do plasma anti phospholipid antibodies in patients with autoimmune haemolytic
      anaemia correlate with reduced levels of erythrocyte complement receptor 1?
AB  - Anti phospholipid antibody (APA), of both IgG and IgM class, was assayed in
      plasma obtained from patients with autoimmune haemolytic anaemia (AHA) and active
      haemolysis. Although plasma APA was elevated in some AHA patients, when compared
      to a normal control population, there was no apparent correlation with levels of
      erythrocyte complement receptor 1 (RBC-membrane CR1) in this patient group.
      However, there appeared to be a correlation between RBC-membrane CR1 and plasma
      IgG APA in a subset of the AHA patients with low RBC-membrane CR1. The potential
      significance of this observation was complicated by the majority of these
      patients having a plasma APA within the normal range. These results suggest that
      the reported inverse correlation between APA and RBC-membrane CR1 may not be
      definitive.

PMID- 8871762
TI  - Manipulation of the Th1/Th2 cell balance: an approach to treat human autoimmune
      diseases?
AB  - Differentiated T cells produce a restricted set of lymphokines, allowing their
      subdivision into two major subsets: Th1 and Th2 cells. This has lead to a new
      paradigm for immunoregulation based on the Th1/Th2 dichotomy. A strict
      compartmentalization of T cells into Th1 and Th2 is clearly an
      oversimplification: regulatory and effector mechanisms in the immune system
      encompass much more than Th1 and Th2 cells. This oversimplification is
      nevertheless useful to carry out experiments designed to test the paradigm. Based
      on results obtained in different experimental models of autoimmune diseases, the
      subdivision of T cells into Th1 and Th2 subsets has been extended to suggest that
      Th1 cells contribute to the pathogenesis of several organ-specific autoimmune
      diseases, whereas Th2 cells may inhibit disease development. Although more slowly
      and maybe less clearly, a similar dichotomy is starting to emerge in human
      autoimmune diseases. It will soon be possible to formally test immunointervention
      based on Th1/Th2 cell manipulation in clinical situations: the tools and a
      conceptual frame are already available. In this review we will examine two key
      factors affecting the Th1/Th2 balance: antigen and the role of cytokines
      influencing the development of Th1 and Th2 cells. The rational manipulation of
      these two variables may ultimately lead to an effective control of Th1 and Th2
      cells potentially able to alter the natural course of human autoimmune diseases.

PMID- 8871763
TI  - Thymus atrophy and changes in thymocyte subpopulations of BN rats with mercury
      induced renal autoimmune disease.
AB  - Administration of low doses of mercury induces autoantibodies to laminin and
      autoimmune glomerulonephropathy in BN, MAXX and DZB rats as well as in (BN x
      LEW)F1 hybrids. LEW strain rats are resistant to these immunotoxic effects.
      Susceptible rats also show lymphoid hyperplasia in spleen and lymph nodes and
      severe thymic atrophy. It is still uncertain whether these mercury-induced
      changes have any role in the induction of autoimmune responses to laminin. In the
      present study, we have examined the effects of mercury on the thymus of
      susceptible and resistant rats. Histological analysis of thymuses from BN rats
      revealed extensive disorganization within 15 days following mercury treatment,
      with loss of demarcation between cortex and medulla. Numbers of thymus cells were
      significantly decreased in both BN and (BN x LEW)F1 hybrid rats injected with
      HgCl2. There was no apparent increase in apoptotic cells in the thymus of these
      animals. By flow cytometry we detected a relative and absolute loss of double
      positive CD4+ CD8+ thymocytes in BN (but not in LEW rats) within 15 days of
      mercury treatment. There was a corresponding increase in the relative proportion
      of single-positive (CD4+ or CD8+) and double-negative CD4- CD8- thymocytes in
      mercury-treated BN rats. Absolute increases in the number of CD4+ single-positive
      thymocytes were also observed. In contrast, mercury-treated LEW rats had no
      changes in thymus architecture or significant decreases in cell numbers. Since
      the thymus is important in both position and negative selection of developing
      thymocytes, immunotoxic effects of mercury on its structure and thymocyte
      subpopulations may have multiple consequences. Alternatively, we suggest the
      hypothesis that autoimmunity (and in particular autoantibodies to laminin) may be
      responsible for the changes observed in the thymus.

PMID- 8871764
TI  - Immunocytochemical localisation of tumor necrosis factor alpha in thyroid tissues
      from patients with neoplastic or autoimmune thyroid disorders.
AB  - It is disputed to what extent tumor necrosis factor-alpha is present in the
      thyroid follicular epithelial cells and/or in the interstitial cells in different
      disorders of the thyroid gland. We describe the immunohistochemical detection of
      tumor necrosis factor-alpha using formaldehyde fixed and paraffin embedded tissue
      and a polyclonal anti-serum with high tumor necrosis factor-alpha neutralising
      activity. We examined the distribution of tumor necrosis factor-alpha in
      interstitial cells and follicular epithelial cells in thyroid carcinomas,
      adenomas, non-toxic multinodular goiters and autoimmune thyroid diseases. Tumor
      necrosis factor-alpha was demonstrated in thyroid follicular epithelial cells,
      most frequently in non-toxic multinodular goiters (six of seven patients) and
      less frequently in adenomas (three of nine patients), papillary carcinomas (two
      of five patients), follicular carcinomas (one of five patients), Hashimoto's
      disease (one of six patients) and Grave's disease (one of seven patients). Tumor
      necrosis factor-alpha producing interstitial cells were found in two thirds of
      patients with all six thyroid diseases.

PMID- 8871765
TI  - Both TH1 and TH2 cytokine mRNAs are expressed in the NOD mouse pancreas in vivo.
AB  - In NOD mice, autoimmune recognition and destruction of pancreatic islet beta
      cells appear to be independently regulated: all mice develop cellular
      infiltration of the islets (insulitis), but not all develop diabetes. The
      destructive potential of the insulitis lesion may depend on the balance between
      the two CD4+ T-cell subsets. TH1 and TH2, that mediate cellular-cytotoxic and
      humoral responses, respectively. With a semi-quantitative reverse transcriptase
      PCR assay, we examined whether the disease process was reflected in the profiles
      of TH1 (IL-2, IFN-gamma and IL-12) and TH2 (IL-4, IL-6 and IL-10) cytokine mRNAs
      expressed in pancreata of NOD mice. Pancreata rather than isolated islets were
      examined to minimize manipulation ex vivo to preserve the expression of cytokine
      transcripts in vivo. At age 6 weeks, when 70% of mice had insulitis, all cytokine
      transcripts were detected in most pancreata, and their expression levels
      corresponded to the degree of insulitis. Similarly, during induction of diabetes
      with cyclophosphamide all transcripts were detected and levels corresponded with
      the degree of insulitis. In one-year-old mice without diabetes, all transcripts
      were detected but levels did not correspond to the degree of insulitis. Thus, in
      pancreata of NOD mice with different degrees of insulitis, we were unable to
      demonstrate, at the RNA level, polarisation of cytokine expression into either a
      TH1 or TH2 profile. This finding does not, however, exclude expression of
      distinct cytokine transcripts by immuno-inflammatory cells within the islet
      lesion, which might be revealed by in situ hybridization.

PMID- 8871766
TI  - Three allelic forms of the human endogenous retrovirus, ERV3, and their
      frequencies in multiple sclerosis patients and healthy individuals.
AB  - A possible association between the endogenous retrovirus, ERV3, and multiple
      sclerosis (MS) was examined. Samples of DNA from 74 MS patients and 159 healthy
      blood donors were subjected to enzymatic amplification followed by single strand
      conformational analysis to detect polymorphisms in the long terminal repeats of
      ERV3. Using this approach we detected six single base pair variations and a drop
      out of a nucleotide. The linkage pattern of these base pair variations enabled us
      to define three allelic forms of ERV3. Polymorphisms exclusively present in the
      group of patients were not found and the distribution of the three allelic forms
      did not differ significantly between the group of controls and the MS group.
      Neither was there a significant difference in the distribution of the three
      alleles between MS patients with the progressive form and patients with
      relapsing/remitting MS. Our results are not in support of an association between
      ERV3 and MS.

PMID- 8871767
TI  - Identification of a novel subset of T lymphocytes in patients with Balkanic
      nephropathy.
AB  - Balkanic Nephropathy (BN) is characterized by: an incidence limited to a
      geographic area: a familial character and a slow progressive evoluation towards
      chronic renal failure associated with the symmetrical reduction of the kidney
      size. The etiology of BN is unknown. The aim of our study was to find out the
      immune alterations in BN pathology. In the BN patients we identified a novel
      subset of the CD3+ CD16+ and CD56+ T cells expressing the phenotypic
      characteristics of both T lymphocytes and NK cells. The analysis of various
      subpopulations of lymphocytes, however, showed no quantitative differences in
      comparison with healthy subjects and healthy subjects from the endemic area.

PMID- 8871768
TI  - Oligoclonality of CD8+ T cells in multiple sclerosis.
AB  - We have shown earlier that CD8+ T cell oligoclonality occurs frequently in normal
      individuals and general exhibits a very diverse repertoire. In order to
      investigate the role of CD8+ T cells in MS, we analysed CD8 oligoclonality in 125
      patients with MS in varying stages of disease. A multiplex PCR assay for CDR3
      length variation was employed to detect oligoclonality in 25 TCRBV
      segments/families. CD8 clonal dominance was found to be frequent in MS.
      Comparison of the CD8 T cell repertoire in MS with that in normal controls
      revealed an increased frequency of oligoclonality involving the TCRBV9, -18 and 
      23 families. Sequence analysis of the TCRs from these clonally dominant CD8+
      cells revealed a high degree of diversity overall. However, we observed one
      instance of identical TCRBV18 sequences in CD8 cells from two unrelated MS
      patients. In addition, several TCRs with motifs homologous to those found in MS
      brain and MBP specific T cell clones in EAE and MS were also detected. Future
      characterization of the function and specificity of these clonally expanded
      populations may provide insight into the nature of immune dysregulation in this
      autoimmune disorder.

PMID- 8871769
TI  - Chronic lithium does not alter human myo-inositol or phosphomonoester
      concentrations as measured by 1H and 31P MRS.
AB  - Lithium may act by decreasing intracellular concentrations of myo-inositol. The
      present study measured the effects of chronic lithium on myo-inositol
      concentrations in volunteers. Eleven subjects received either lithium (n = 7) or
      placebo (n = 4) for 7 days in a double-blind study. Myo-inositol concentrations
      at baseline and day 8 were measured in vivo using 1H magnetic resonance
      spectroscopy (MRS). The results showed that lithium did not alter brain myo
      inositol concentrations compared to placebo. In 5 other subjects we used 1H MRS
      and 31P MRS to measure changes in both myo-inositol and phosphomonoester
      concentrations. This second study showed that lithium did not alter myo-inositol
      or phosphomonoester concentrations. Thus, the present studies do not support the
      hypothesis that lithium significantly affects the brain concentrations of myo
      inositol or phosphomonoesters; however, it is possible these findings represent
      an inability to detect the changes in myo-inositol and phosphomonoester
      concentrations that may have occurred following lithium administration.

PMID- 8871770
TI  - Lack of effect of laboratory-provoked anxiety on plasma homovanillic acid
      concentration in normal subjects.
AB  - The present study was undertaken to investigate if acute anxiety can affect
      plasma concentrations of homovanillic acid (pHVA). Since elevated pHVA levels
      have been associated with severity of schizophrenic symptoms, the results of this
      study will help determine if the pHVA elevations are directly related to
      psychosis or if anxiety is also a contributory factor. Anxiety was provoked in 10
      young normal subjects by a combined paradigm of mental arithmetic task and threat
      of electrical shock. A significant increase in self-ratings of anxiety, blood
      pressure, and plasma levels of norepinephrine, 3-methoxy-4
      hydroxyphenylethyleneglycol and growth hormone indicated that the paradigm used
      was effective in provoking anxiety; however, anxiety did not affect pHVA
      concentrations. The results may support the notion that increased pHVA levels in
      severely ill schizophrenic patients are related to the schizophrenic
      pathophysiology rather than to anxiety.

PMID- 8871771
TI  - Acute and long-term effectiveness of clozapine in treatment-resistant psychotic
      depression.
AB  - The treatment of refractory major depression, including the psychotic subtype, is
      a therapeutic challenge. Three cases of resistant psychotic depression were
      treated with clozapine monotherapy, an atypical antipsychotic drug effective in
      treatment-resistant schizophrenia and mania. Both psychotic and mood symptoms
      responded well to clozapine monotherapy, although response was delayed in one
      case. Tardive dyskinesia improved markedly, and tardive dystonia improved
      moderately in one patient. No patient relapsed during a follow-up period of 4-6
      years of clozapine treatment. Clozapine was well-tolerated with few side effects.
      These observations suggest controlled trials of clozapine in the treatment of
      psychotic depression that fails to respond to electroconvulsive therapy or
      typical neuroleptics plus tricyclic antidepressants are indicated. The same is
      true for the use of clozapine in maintenance treatment for psychotic depression
      in those cases in which typical neuroleptic drugs are required, in order to
      reduce the risk of tardive dyskinesia and dystonia.

PMID- 8871772
TI  - Circadian rest-activity rhythm disturbances in Alzheimer's disease.
AB  - Previous studies showed circadian rhythm disturbances in patients with
      Alzheimer's disease. Rest-activity rhythm disturbances manifest themselves
      through a fragmentation of the rhythm, a weak coupling with Zeitgebers, and high
      levels of activity during the night. The aim of the present study was to
      investigate which factors contribute to the presence of these disturbances.
      Therefore, several rest-activity rhythm, constitutional, and environmental
      variables were assessed in a heterogeneous group of 34 patients with Alzheimer's
      disease, including presenile and senile patients living at home or in a nursing
      home, as well as in 11 healthy controls. Circadian rest-activity rhythm
      disturbances were most prominent in institutionalized patients. Regression
      analyses showed the involvement of the following variables. First stability of
      the rest-activity rhythm is associated with high levels of daytime activity and
      high levels of environmental light resulting from seasonal effects as well as
      from indoor illumination. Presenile onset contributed to instability of the
      rhythm. Second, fragmentation of periods of activity and rest is associated with
      low levels of daytime activity, and is most prominent in moderately severe
      dementia. Third, night-time activity level is higher during the times of the year
      when the days are getting shorter and lower when the days are growing longer.
      These findings indicate that rest-activity rhythm disturbances may improve by
      increasing environmental light and daytime activity, an assumption for which
      empirical evidence has recently been published.

PMID- 8871773
TI  - Platelet serotonergic markers and Tridimensional Personality Questionnaire
      measures in a clinical sample.
AB  - A group of patients with major depressive disorder, with and without comorbid
      obsessive-compulsive disorder, completed the Tridimensional Personality
      Questionnaire (TPQ). Harm Avoidance scores were found to be high compared to
      published age-matched norms and to display a significant positive correlation
      with Hamilton Depression Rating Scale scores. Platelet 125I-lysergic acid
      diethylamide (125I-LSD) and 3H-paroxetine binding Bmax values were measured to
      test Cloninger's hypothesis that Harm Avoidance scores would correlate
      significantly with measures of serotonergic function. A significant inverse
      correlation was found between Harm Avoidance scores and 125I-LSD Bmax values.
      Correlations between 3H-paroxetine Bmax values and TPQ scale scores were not
      significant. These results suggest an alternative view of the literature relating
      platelet 5-hydroxytryptamine-2a receptors and mood disorders in that the
      temperament dimension, Harm Avoidance, may explain prior inconsistencies
      involving links with depression and suicidality.

PMID- 8871774
TI  - Comparative evaluation of two self-report Mania Rating Scales.
AB  - Two brief patient-rated scales, the Internal State Scale (ISS) and the Self
      Report Manic Inventory (SRMI), have been shown to reliably diagnose mania. In the
      current study we further evaluated the utility of these scales relative to each
      other and to the observer-rated Young Mania Rating Scale (YMRS), for quantifying
      the severity of manic/hypomanic symptoms cross-sectionally and over time, in 20
      patients with rapid-cycling bipolar disorder. The self-report scales correlated
      well with each other and with the YMRS, but each covered a somewhat different
      domain of the manic syndrome. The SRMI and the ISS were more sensitive than the
      YMRS to the mood fluctuations in the euthymic to hypomanic range observed in our
      subjects. Used in tandem, the two self-report scales may find application in
      clinical research with outpatients with bipolar disorder, and as an adjunct to
      clinical monitoring in this patient population.

PMID- 8871775
TI  - Effect of acute ethanol on auditory and visual event-related potentials: a review
      and reinterpretation.

PMID- 8871776
TI  - Organic psychosis linked to chronic tonsillitis and subsequent encephalitis: a
      probable autoimmune process.

PMID- 8871777
TI  - Backward masking in schizophrenia: relationship to medication status,
      neuropsychological functioning, and dopamine metabolism.

PMID- 8871778
TI  - Magnetoencephalographic evidence of abnormal early auditory memory function in
      schizophrenia.

PMID- 8871779
TI  - Cholesterol lowering and cerebrospinal fluid neurotransmitters: increased levels
      of the anxiogenic cholecystokinin-tetrapeptide during simvastatin administration
      to healthy male volunteers.

PMID- 8871780
TI  - Excess tyrosine hydroxylase restriction fragment length polymorphism homozygosity
      in unipolar but not bipolar patients: a preliminary report.

PMID- 8871781
TI  - Tricyclic-induced musical hallucinations.

PMID- 8871782
TI  - Is post-lumbar-puncture headache influenced by the menstrual cycle?

PMID- 8871783
TI  - A review of brain aromatase cytochrome P450.
AB  - Aromatase cytochrome P45 (P450AROM) enzyme activity catalyzes the conversion of
      androgens to estrogens in specific brains areas. During central nervous system
      development local estrogen formation influences the sexual differentiation of
      neural structures (i.e., by increasing neurite growth and establishing neural
      circuitry) and modulates neuroendocrine/reproductive functions and sexual
      behavior. More than 20 years ago, in 1970, Naftolin et al. provided preliminary
      direct evidence for the aromatization of androgens by central neuroendocrine
      tissues. This work created the foundation for the brain aromatase hypothesis. A
      review of past and recent data reveals the importance of brain aromatase in the
      development and function of the central nervous system. This review re-examines
      the aromatase hypothesis in light of recent data and a theoretical proposal is
      presented in reference to the aromatase mechanism. The metabolic pathway of
      androgen metabolism by the aromatase cytochrome P450 pathway, cell type,
      distribution, developmental profile, and regulation of brain aromatase is also
      presented. The complex nature of brain aromatase is exemplified by recent
      molecular biology studies examining the expression of aromatase cytochrome P450
      during prenatal/postnatal development. Data derived from these studies provide
      insight into the regulation of the brain aromatase cytochrome P450 gene and
      suggest an additional level of control for the expression of brain aromatase.
      These findings present evidence for the utilization of alternative promoter(s) in
      man and rodents in driving aromatase gene expression in brain. It is clear that
      molecular mechanism(s) account for the diverse expression of aromatase in
      different neural tissue sites and during various physiological states or
      developmental periods. Therefore, further study is necessary in order to
      understand the significance of the regulation of local estrogen biosynthesis by
      the aromatase cytochrome P450 gene during prenatal and postnatal development due
      to the dramatic impact these estrogen molecules have on neural development and
      their influence on reproductive function and behavior.

PMID- 8871784
TI  - Neuropeptides-immunoreactivity and their mRNA expression in kindling: functional
      implications for limbic epileptogenesis.
AB  - Recent studies have demonstrated that neuropeptide expression in forebrain
      neurons is responsive to changes in physiological activity. This is particularly
      true in the hippocampus where the expression of various neuropeptides has been
      reported to change in distinct neuronal populations in response to seizure
      activity. The aim of this work is to review and integrated the information on the
      pathological changes and functional modifications in neuropeptide systems of the
      hippocampal formation in kindling and other models of limbic epilepsy. This will
      be done by presenting a study in which we investigated the changes in the
      expression of somatostatin, neuropeptide Y (NPY), neurokinin B (NKB) and
      cholecystokinin-octapeptide (CCK) in the rat hippocampal principal neurons during
      and after kindling of the hippocampus using immunocytochemistry and in situ
      hybridization analysis of mRNA. NPY-IR was transiently expressed in the granule
      cells/mossy fibres after the preconvulsive stage 2 and 2 days but not 1 week
      after three consecutive tonic-clonic seizures (stage 5). A more pronounced
      increase was observed in NKB-IR lasting 1 week after kindling acquisition. Only
      the NKB mRNA expression was enhanced in granule cells at these intervals. At
      stages 2 and 5, somatostatin- and NPY-IR and their mRNA levels were markedly
      increased in interneurons in the deep hilus and in the polymorphic cell layer and
      their presumed projections to the outer molecular layer of the dentate gyrus. NKB
      and CCK-IR and their mRNAs were highly expressed in basket cells at both stages
      of kindling. Their IR was increased in the inner molecular layer of the dentate
      gyrus in the ventral hippocampus. Peptide-containing neurons in the hilus
      appeared well preserved in spite of a reduction of Nissl stained cells by 24 % in
      the stimulated and contralateral hippocampus at stage 5. In the hippocampus
      proper, somatostatin and NPY-IR were enhanced in the stratum lacunosum molecular
      while CCK-IR fibres and its mRNA were particularly expressed in the pyramidal
      cell layer. The number of Somatostatin-, NKB- and CCK-IR cells was increased in
      the subiculum. The intensity of these changes was similar 2 days after stages 2
      or 5 of kindling. Less pronounced effects were observed 1 week after kindling
      completion. These results, in the frame of the literature data, suggest that
      lasting functional changes occur in distinct neuropeptide-containing neurons
      during limbic epileptogenesis. This may have profound effects on synaptic
      transmission and contribute to modulate hippocampal excitability.

PMID- 8871785
TI  - An alternative to the LTP orthodoxy: a plasticity-pathology continuum model.
AB  - Long-term potentiation (LTP) is probably the most widely studied form of synaptic
      plasticity in the mammalian central nervous system. In the early descriptions,
      the term referred to a sustained increase in synaptic response following a brief
      high-frequency electrical tetanus. Apparently unique properties of the phenomenon
      triggered considerable excitement in the field: for many, LTP offered the promise
      of a potential substrate for learning and/or memory. In the more than 20 years
      since LTP was first discovered, investigators motivated by this promise have
      described a vast array of molecules and processes that may be involved in LTP
      induction and maintenance. And yet, the mechanisms by which LTP occurs have not
      been resolved. Instead, the compiled results have uncovered layer upon layer of
      intricacy, including multiple LTP forms and multiple molecular cascades involved
      in LTP expression. The generally stated thesis that LTP equates to learning
      and/or memory at a synaptic level has not faced a serious challenge despite the
      fact that workers in the field have not provided an unambiguous correlation of
      LTP with either. A number of investigators have now shifted their attention to a
      newer form of synaptic modification, long-term depression (LTP). Whatever studies
      of LTD reveal, it is clear that the fundamental questions about LTP remain
      unanswered: what is it really and what, if anything, is it used for? In this
      review, we summarize the data concerning putative LTP mechanisms and the evidence
      for LTP's role in learning and memory. We show that extant models are not
      sufficient to account for the various forms of LTP and that the experimental
      evidence does not justify the view that LTP equates to learning and memory.
      Instead, we suggest that LTP can be related to other forms of synaptic
      modification, e.g., LTD and kindling, in a neuroplasticity/pathology continuum of
      events. In particular, we suggest that neurotransmitter receptor regulation may
      be a key element leading to synaptic modification: in the adult nervous system,
      homeostatic receptor regulation normally compensates for alterations in synaptic
      input, while in the developing nervous system a form of 'homeodynamic' receptor
      regulation prevails. Our model proposes that homeodynamic receptor regulation
      leading to an LTP-like effect triggers, or acts in concert with, synaptogenesis
      to allow young neurons to modify response characteristics in response to altered
      input. In contrast, some forms of LTP in adult neurons may represent a 'failed'
      form of receptor regulation whose final outcome is neural death. The model
      suggests a series of experimentally verifiable hypotheses.

PMID- 8871786
TI  - China: the epidemiology of mental illness.

PMID- 8871787
TI  - Scientific status of recovered memories.

PMID- 8871788
TI  - Genomics: the next psychiatric revolution?

PMID- 8871789
TI  - The mental health residential care study: classification of facilities and
      description of residents.
AB  - BACKGROUND: The NHS is no longer a virtual monopoly provider of mental health
      residential care. This makes it difficult to assess the volume, range and
      adequacy of local provision. METHOD: Local data collectors used standard
      instruments to collect detailed information about 368 facilities (with 1951
      residents) providing mental health residential care in eight districts. Because
      local definitions were inconsistent, facilities were reclassified on the basis of
      facility size and extent of day and night cover. The eight categories of
      accommodation are compared on levels of staffing, staff qualifications and the
      characteristics of their residents. RESULTS: There was a nearly threefold
      variation between districts in the total number of residential places available
      per unit of population, and even greater variation in the number of places with
      24-hour waking cover. Most residents have long-term, severe mental illness and
      severe impairment. Long-stay wards accommodate people who pose greater risk of
      violence than do the two types of non-hospital facility with 24-hour waking cover
      (P < 0.001). The former also employ a much greater proportion of staff with
      formal care qualifications and, in particular, nursing qualifications than the
      latter (49% v. 15%, P < 0.001). CONCLUSIONS: It is suggested that one consequence
      of the diversification in provision of mental health residential accommodation
      has been a relative reduction in the proportion of provision available to the
      most severely disabled. This might apply particularly to those who pose a risk of
      acting violently.

PMID- 8871790
TI  - The neural correlates of inner speech and auditory verbal imagery in
      schizophrenia: relationship to auditory verbal hallucinations.
AB  - BACKGROUND: Auditory verbal hallucinations are thought to arise from the
      disordered monitoring of inner speech (thinking in words). We tested the
      hypothesis that a predisposition to verbal auditory hallucinations would be
      associated with an abnormal pattern of brain activation during tasks which
      involved the generation and monitoring of inner speech. METHOD: The neural
      correlates of tasks which engaged inner speech and auditory verbal imagery were
      examined using positron emission tomography in (a) schizophrenic patients with a
      strong predisposition to auditory verbal hallucinations (hallucinators), (b)
      schizophrenic patients with no history of hallucinations (nonhallucinators), and
      (c) normal controls. RESULTS: There were few between-group differences in
      activation during the inner speech task. However, when imagining sentences spoken
      in another person's voice, which entails the monitoring of inner speech,
      hallucinators showed reduced activation in the left middle temporal gyrus and the
      rostral supplementary motor area, regions which were strongly activated by both
      normal subjects and nonhallucinators (P < 0.001). Conversely, when
      nonhallucinators imagined speech, they differed from both hallucinators and
      controls in showing reduced activation in the right parietal operculum.
      CONCLUSIONS: A predisposition to verbal hallucinations in schizophrenia is
      associated with a failure to activate areas implicated in the normal monitoring
      of inner speech, whereas the absence of a history of hallucinations may be linked
      to reduced activation in an area concerned with verbal prosody.

PMID- 8871791
TI  - Life events and primary affective disorders. A one year prospective study.
AB  - BACKGROUND: Unipolar and bipolar patients with a chronic illness pattern were
      investigated to determine whether they experienced a higher number of life events
      prior to the onset of recurrent affective episodes. METHOD: The study
      participants consisted of 27 recovered bipolar patients, 24 recovered unipolar
      patients and 26 healthy control subjects. Life events and psychiatric status were
      assessed by bimonthly interviews over the period of one year using the Inventory
      for Recent Life Events and the Research Diagnostic Criteria. RESULTS: In both
      unipolar and bipolar patients, analyses revealed no significant differences in
      the number of life events experienced, irrespective of whether the patients had
      presented with a depressive episode of at least minor intensity during the study
      (all P > 0.1). Specifically, an increase in marital problems was observed in
      bipolar patients prior to the onset of recurrent hypomanic and manic episodes (P
      = 0.06). CONCLUSION: The causal association between life events and the onset of
      depression, shown to be relevant in non-chronically depressed subjects, does not
      apply in chronic affective disorders. In addition, our results suggest that
      marital events have an impact on the onset of recurrent hypomanic and manic
      episodes.

PMID- 8871792
TI  - The bereavement response: a cluster analysis.
AB  - BACKGROUND: Literature and clinical experience suggest that some people
      experience atypical, complicated or pathological bereavement reactions in
      response to a major loss. METHOD: Three groups of community-based bereaved
      subjects--spouses (n = 44), adult children (n = 40), and parents (n = 36)--were
      followed up four times in the 13 months after a loss. A 17-item scale of core
      bereavement times was developed and used to investigate the intensity of the
      bereavement response over time. RESULTS: Cluster analysis revealed a pattern of
      bereavement-related symptoms approximating a syndrome of chronic grief in 11
      (9.2%) of the 120 subjects. None of the respondents displayed a pattern
      consistent with delayed or absent grief. CONCLUSIONS: In a non-clinical community
      sample of bereaved people, delayed or absent grief is infrequently seen, unlike
      chronic grief, which is demonstrated in a minority.

PMID- 8871793
TI  - The entry of mentally disordered people to the criminal justice system.
AB  - BACKGROUND: The police are the gatekeepers to the criminal justice system (CJS).
      It is agreed that where possible mentally ill people should be diverted to
      psychiatric care. The purpose of this investigation was to determine what factors
      were associated with the entry of obviously mentally ill people into the CJS.
      METHOD: The population of all detainees arrested in seven London police stations
      was observed to determine the presence of obvious mental illness. All detainees
      regarded as ill or known to have significant psychiatric histories were followed
      through the CJS to court disposal. Defendants diagnosed as psychotic by court
      liaison psychiatrists were identified and the circumstances of their arrest and
      detention examined. RESULTS: Of all police detainees observed, 1.4% were found to
      be acutely ill. Diversion of obviously ill detainees was common practice. The
      factor most strongly associated with entry to the CJS was the presence of
      violence at time of arrest. Other factors were the persistence of (petty)
      offending and the operation of court warrants issued as a result of the person's
      failure to appear at court when required to do so. CONCLUSIONS: Both police and
      courts are well aware of the inappropriateness of custody for acutely ill people
      and efforts are made to divert such people out of the CJS. Persistent petty
      offenders are often being recycled from the street to police station to court and
      back to the street without the benefit of care. A dedicated facility is
      recommended in central London to meet this need.

PMID- 8871794
TI  - Individual behavioural-cognitive therapy v. marital therapy for depression in
      maritally distressed couples.
AB  - BACKGROUND: Depressed patients are often characterised by marital distress, but
      few studies investigate the effects of marital therapy on depressed mood and
      relationship dysfunction. METHOD: Twenty-seven depressed patients experiencing
      marital distress were randomly assigned to either individual behavioural
      cognitive therapy or marital therapy. The individual treatment condition focused
      on depressed mood, behavioural activity and dysfunctional cognitions, whereas in
      the marital condition the partner was involved in the treatment and the focus was
      on the communication process in the marital relationship. MANOVAs revealed that
      treatment led to statistically significant improvements in depressed mood,
      behavioural activity and dysfunctional cognitions, an increase in relationship
      satisfaction and improvement of communication in patients and spouses. A
      significant interaction effect was found, showing that marital therapy had more
      impact on relationship variables than the individual treatment. CONCLUSION: Both
      individual cognitive-behaviour therapy and marital therapy lead to less
      depressive complaints, and both treatment conditions have a positive effect on
      the relationship, although the effect on the relationship is significantly
      stronger in couples who were tested by marital therapy compared with patients who
      were treated individually.

PMID- 8871795
TI  - A controlled trial of cognitive-behavioural treatment of hypochondriasis.
AB  - BACKGROUND: Hypochondriasis is a distressing disorder for which there is no
      adequate established treatment. This study evaluates the effect of cognitive
      behavioural treatment of hypochondriasis, compared with a waiting list control.
      METHOD: Thirty-two patients were randomly assigned to either cognitive
      behavioural therapy or a no treatment waiting list control. Cognitive-behavioural
      treatment consisted of 16 individual treatment sessions over a four-month period.
      The waiting list control lasted for four months and was followed by 16 sessions
      of cognitive-behavioural treatment. Assessments were made before allocation and
      after treatment or waiting list control. Patients who had cognitive-behavioural
      treatment were reassessed three months after completion of treatment. RESULTS:
      Paired comparisons on post-treatment/wait scores indicated that the cognitive
      behavioural group showed significantly greater improvements than the waiting list
      on all but one patient rating, all therapist ratings and all assessor ratings.
      After three months the benefits of therapy were maintained. CONCLUSIONS:
      Cognitive-behavioural treatment is an effective therapy for hypochondriasis.
      Implications of the study are discussed.

PMID- 8871796
TI  - Body dysmorphic disorder. A survey of fifty cases.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) consists of a preoccupation with an
      'imagined' defect in appearance which causes significant distress or impairment
      in functioning. There has been little previous research into BDD. This study
      replicates a survey from the USA in a UK population and evaluates specific
      measures of BDD. METHOD: Cross-sectional interview survey of 50 patients who
      satisfied DSM-IV criteria for BDD as their primary disorder. RESULTS: The average
      age at onset was late adolescence and a large proportion of patients were either
      single or divorced. Three-quarters of the sample were female. There was a high
      degree of comorbidity with the most common additional Axis l diagnosis being
      either a mood disorder (26%), social phobia (16%) or obsessive-compulsive
      disorder (6%). Twenty-four per cent had made a suicide attempt in the past.
      Personality disorders were present in 72% of patients, the most common being
      paranoid, avoidant and obsessive-compulsive. CONCLUSIONS: BDD patients had a high
      associated comorbidity and previous suicide attempts. BDD is a chronic
      handicapping disorder and patients are not being adequately identified or treated
      by health professionals.

PMID- 8871797
TI  - Deliberate self-poisoning and self-injury in children and adolescents under 16
      years of age in Oxford, 1976-1993.
AB  - BACKGROUND: Deliberate self-harm (DSH) is common in adolescents in the United
      Kingdom and suicide has greatly increased in frequency in older male adolescents.
      There is, however, very little information about DSH in older children and young
      adolescents. METHOD: Analysis of data collected by the Oxford Monitoring System
      for Attempted Suicide between 1976 and 1993 for all cases of DSH in under 16-year
      olds referred to the general hospital in Oxford. RESULTS: Seven hundred and fifty
      five individuals were involved in 854 episodes of DSH. There were very few cases
      under 12 years of age but after that the behaviour increased greatly in frequency
      with each year of age, especially in girls. Eighty-five per cent were girls, the
      sex ratio being 5.7 girls to each boy. Most cases involved self-poisoning. During
      the final six years of the study period paracetamol was involved in 54.7% of
      overdoses, compared with 19.5% in 1976-1981. A minority of individuals had had
      previous psychiatric treatment. The most frequent problems were relationship
      difficulties with parents, followed by difficulties with friends, school and
      social isolation. Among those who reported previous episodes of DSH, in the
      majority of cases these had not come to medical attention. Repetition of self
      harm occurred in 9.4% of cases within a year of an episode and 19.3% during the
      overall study period. There was some indication that repetition was most common
      in youngsters discharged from the Accident and Emergency Department without a
      psychiatric assessment. CONCLUSIONS: DSH in under 16-year-olds is not uncommon
      and there is evidence that it occurs far more frequently in the community than is
      reflected in general hospital figures. The problem of paracetamol self-poisoning
      in this age group needs to be addressed. A psychiatric assessment should be
      performed in all cases coming to the general hospital.

PMID- 8871798
TI  - Symptoms of the schizophrenic negative syndrome.
AB  - BACKGROUND: The aim was an investigation of the symptom composition of the
      negative syndrome of schizophrenia. METHOD: A hundred schizophrenic patients were
      assessed with various rating scales for positive and negative symptoms and
      typological criteria. A subgroup with a negative syndrome was defined, and a
      discriminant analysis performed using symptoms from the Scale for the Assessment
      of Negative Symptoms (SANS) as discriminant variables. RESULTS: The discriminant
      function classified 92% of patients correctly. All but four SANS symptoms
      (inappropriate affect, both attentional items and blocking) were significantly
      correlated with the discriminant function. CONCLUSIONS: With the exception of
      some items, the SANS seems to capture adequately the negative syndrome of
      schizophrenia.

PMID- 8871799
TI  - Age at onset in schizophrenia and risk of illness in relatives. Results from the
      Roscommon Family Study.
AB  - BACKGROUND: For many common medical and neuropsychiatric disorders, early age at
      onset reflects high familial liability to illness. However, for schizophrenia,
      most studies do not find such a relationship. METHOD: Using Cox proportional
      hazard modes, we investigate this question in the epidemiologically-based
      Roscommon family study. RESULTS: No relationship was found between age at onset
      in schizophrenic probands and the hazard rate for schizophrenia in their
      relatives. Similar results were obtained when the definition of illness was
      expanded to include schizoaffective disorder and other non-affective psychoses.
      CONCLUSIONS: For schizophrenia, a 'common-sense' model for age of onset (i.e.
      those with highest familial liability to illness succumb first while those with
      lower liability survive longer before falling ill) does not seem to apply. Our
      results are more consistent with a model in which variation in age at onset of
      schizophrenia is due to random developmental effects or to environmental
      experiences unique to the individual.

PMID- 8871800
TI  - Prevalence and cluster typology of maladaptive behaviors in a geographically
      defined population of adults with learning disabilities.
AB  - BACKGROUND: Maladaptive behaviours are frequently present in individuals with
      learning disabilities; however, their prevalence varies between studies and the
      aetiology, classification and most appropriate management of such behaviors
      remain unclear. The aims of the study were twofold: firstly to determine the
      prevalence of maladaptive behaviours, and secondly to develop a classification
      typology. METHOD: A population of 2202 adults with learning disabilities was
      surveyed to determine the prevalence of maladaptive behaviours. These were
      subjected on the basis of 13 behavioural characteristics to cluster analysis. The
      clusters were further examined in respect of secondary variables. RESULTS: Over
      60% of individuals demonstrated the presence of at least one maladaptive
      behaviour and in 40% this problem was of either severe degree or frequent
      occurrence. Men were more likely to demonstrate physical aggression, property
      destruction, tantrums and verbal abuse than women. Although some severe
      maladaptive behaviours diminished with age, many persisted through all age
      groups. Six behavioural clusters were devised which demonstrated face validity
      and which differed in respect of demographic and developmental variables, and the
      prevalence of maladaptive habits and autistic symptoms. CONCLUSIONS: These
      findings demonstrate a high prevalence of maladaptive behaviours and
      'objectionable habits' among people with learning disabilities. A classification
      of behavioural symptoms may be possible on the basis of symptom clusters.

PMID- 8871801
TI  - Cumulative incidence and prevalence of childhood autism in children in Japan.
AB  - BACKGROUND: An epidemiological survey of childhood autism as defined in ICD-10
      Research Criteria was conducted in the northern part of Yokohama, Japan. METHOD:
      The routine health checkup for 18-month-old children served as the initial mass
      screening, and all facilities which provide child care services function to
      detect all cases with childhood autism and refer them to the Yokohama
      Rehabilitation Centre. RESULTS: Cumulative incidence of childhood autism up to 5
      years of age among the birth cohort of 1988, and prevalence on 1 January 1994,
      among residents born in 1988 were estimated RESULTS: Cumulative incidence and
      prevalence were 16.2 per 10,000 and 21.1 per 10,000, respectively. Children with
      high-functioning autism who had IQs of 70 and over constituted approximately half
      of all the children with childhood autism. CONCLUSION. It was confirmed through
      better detection of high-functioning cases that childhood autism in Japan is more
      common than formerly estimated.

PMID- 8871802
TI  - Physical and psychiatric comorbidity in general practice.
AB  - BACKGROUND: The aim of this study was to determine the association between
      physical and psychiatric morbidity among general practice patients and to explore
      the influence of possible intervening variables. METHOD: Physical and psychiatric
      morbidity in 1620 consecutive patients attending their general practitioner (GP)
      was assessed using a two-stage design. Ninety-four per cent of the patients (n =
      1523) were successfully screened using the General Health Questionnaire (GHQ-12);
      428 of the 602 patients (71%) eligible for the second stage were interviewed
      using the Composite International Diagnostic Instrument adapted for use in
      primary health care (CIDI-PHC), the Brief Disability Questionnaire (BDQ) and the
      Groningen Social Disability Schedule (GSDS) to assess psychiatric, physical and
      social status. Assessments of physical and psychiatric morbidity were also
      obtained from the patients' GPs. RESULTS: There was a significant association
      between physical and psychiatric morbidity, although patients with four symptoms
      or less of physical illness were no more likely to be psychiatric cases than
      those with none. The association was accounted for by patients at the severe end
      of the physical continuum with five or more medically explained somatic symptoms:
      these were twice as likely to be psychiatric cases as those with no such
      symptoms. Female gender, social disability and physical disability were all
      significantly more likely to be associated with psychiatric disorder, whether
      measured by GP or research interview; and these relationships remained after the
      data were corrected for age differences. CONCLUSIONS: Patients in general
      practice with moderate to severe physical morbidity are at increased risk of
      developing psychiatric illness, and when medical illness is present, psychiatric
      symptoms are more severe. As physical and psychiatric comorbidity is relatively
      common in general practice, the specific needs of these patients should receive
      greater attention.

PMID- 8871803
TI  - A genetic linkage study of the D2 dopamine receptor locus in heavy drinking and
      alcoholism.
AB  - BACKGROUND: Reports of an association between restriction fragment length
      polymorphisms (RFLPs) at the dopamine D2 receptor (DRD2) locus and alcoholism
      have suggested involvement of that locus in the aetiology of alcoholism. METHOD:
      Sib pair linkage analyses were conducted in families multiply affected by
      alcoholism, using both the Taql 'A' RFLP and a microsatellite repeat polymorphism
      at the DRD2 locus. RESULTS: The 'Identical By Descent' analysis provided
      significant evidence of an effect of the DRD2 locus on the liability to develop
      heavy drinking (P < 0.0016) and Research Diagnostic Criteria alcoholism (P <
      0.0003) in the first sample of families studied. However, this result was
      explicable by the segregation of alleles in a single large sibship, and it was
      not replicated in a second sample of families. CONCLUSIONS: The results do not
      support linkage between the DRD2 locus and alcoholism in most of the families
      studied. It remains possible that this locus influences the predisposition to
      alcoholism in some families.

PMID- 8871804
TI  - 'Audible thoughts' and 'speech defect'.

PMID- 8871805
TI  - 'Audible thoughts' and 'speech defect'.

PMID- 8871806
TI  - 'Audible thoughts' and 'speech defect'.

PMID- 8871807
TI  - Tricyclics and SSRIs.

PMID- 8871808
TI  - Lithium and weight gain.

PMID- 8871809
TI  - Influenza and schizophrenia.

PMID- 8871810
TI  - No evidence for association between CNTF null mutant allele and schizophrenia.

PMID- 8871811
TI  - Should the administration of ECT during clozapine therapy be contraindicated?

PMID- 8871812
TI  - In memoriam of Daniel Mazia (1913-1996).

PMID- 8871813
TI  - Functional significance of the outer dense fibers of mammalian sperm examined by
      computer simulations with the geometric clutch model.
AB  - The flagella of mammalian sperm possess certain structural characteristics that
      distinguish them from simple flagella. Most notable of these features are the
      sheath (surrounding the axoneme), the outer dense fibers of ODFs (that are
      attached to the outer doublets), and the connecting piece (which anchors the ODFs
      at the base of the flagellum). In this study, the significance of these
      specialized axonemal elements is explored. Their impact on microtubule sliding
      and force production within the axoneme is specifically analyzed. A working
      hypothesis is developed based on the premise that forces produced by interdoublet
      sliding are transferred to the ODFs. In this way, the torque required to bend the
      flagellum is developed between the ODFs, which are anchored in the connecting
      piece. This working hypothesis was incorporated into the pre-existing "geometric
      clutch" model that earlier simulated only cilia and simple flagella. The
      characteristic length and stiffness of bovine sperm flagella were specified as
      modelling parameters. Additionally, the inter-ODF spacing of bull sperm was
      incorporated to calculate doublet sliding and bending torque. The resultant
      computer-simulated pattern of flagellar beating possesses many of the attributes
      of the beat of a live bull sperm flagellum. Notably, this life-like simulation
      can be produced using parameters for the central axonemal "motor" that are
      comparable to those effective in modelling a simple flagellum. In the proposed
      scheme, the accessory structures of the mammalian sperm axoneme provide increased
      stiffness while at the same time providing a means to proportionately raise the
      bending torque to overcome that additional flexural rigidity. This capacity is
      due to the inter-ODF distances being larger than the corresponding interdoublet
      spacings. If force is transmitted to the flagellar base by way of the ODFs, then
      the larger effective diameter generates both a greater bending torque and
      increased interdoublet sliding. This has the interesting effect of consolidating
      the energy from more dynein cross-bridges into the production of a single bend.
      Consequently. greater bending torque development is permitted than would be
      possible in a simple flagellum. In This way, the same 9 + 2 organization of a
      simple flagellum can power a much larger (and stiffer) version than would
      otherwise be possible.

PMID- 8871814
TI  - Ca(2+)-induced tension development in the stalks of glycerinated Vorticella
      convallaria.
AB  - We have developed a method of measuring the isometric tension in glycerinated
      stalks of Vorticella convallaria. Using this method, we measured tension vs. pCa
      relations in glycerinated V. convallaria stalks. The maximum isometric tension
      was 4 x 10(-8) N on average. The Hill's parameter, n, which is the number of
      calcium ions bound simultaneously and cooperatively to a contractile element (a
      force generating element), is approximately 3.2 when the Ca2+ concentration is
      increased and 2.5 when it is decreased. In order to estimate the efficiency of
      the energy conversion of Ca2+ binding to mechanical work, we measured the Ca(2+)
      induced Carnot cycle in the Vorticella stalk. The energy efficiency was
      tentatively estimated to be about 7%. With this method, we have also succeeded in
      measuring the isometric tension of isolated spasmoneme, the rubber-like
      contractile fibrous organelle in the stalk. The maximum tension of spasmoneme was
      approximately one tenth that of the glycerinated stalk. We speculate that the
      isolated spasmoneme was only partially functional due to damage sustained when it
      was pulled out of the stalk.

PMID- 8871816
TI  - Human foetal lung (IMR-90) cells: myofibroblasts with smooth muscle-like
      contractile properties.
AB  - Single cells displaying many characteristics in common with smooth muscle are now
      being identified in many organs. Although their origin remains elusive, they are
      nonetheless known to play a major role in fibroproliferative diseases and stromal
      reactions by virtue of their contractile properties. We have investigated the
      contractile properties and expression of smooth muscle-associated proteins in
      such a cell line derived from human foetal lung (IMR-90). For almost two decades,
      these cells have served as model fibroblasts in a wide variety of studies. And
      yet, IMR-90 cells manifest many features characteristic of differentiated smooth
      muscle cells: they exhibit the same elongated, slender form and the strikingly
      regular, longitudinal alignment of their actin-attachment sites, which are
      indispensable for coordinated contraction. Moreover, these adhaerens junctions
      also contain metavinculin, the smooth muscle analogue of vinculin, the stable
      expression of which has not previously been demonstrated in cultured cells. Since
      sm 22, as well as the smooth muscle-associated alpha-actin isoform and calponin
      are also expressed, IMR-90 cells must now be classified as myofibroblasts. When
      cultivated on a rubbery silicon surface, IMR-90 cells respond to stimulation with
      a rate of contraction which is considerably faster than that exhibited by
      fibroblasts derived from other established lines. Taken together, the regular
      longitudinal orientation of the adhaerens junctions, the stable expression of
      metavinculin, and the rapid speed of shortening in IMR-90 cells suggest, by
      implication, that the periodicity of actin attachment sites is a fundamental
      determinant of contractile efficiency in smooth muscle cells; this spacing may be
      mediated by metavinculin.

PMID- 8871815
TI  - Novel form of actin-based motility transports bacteria on the surfaces of
      infected cells.
AB  - Enteropathogenic Escherichia coli (EPEC) attach to cells (attachment) lining the
      intestine and induce a decrease in the number of the cells' microvilli
      (effacement). This attachment and effacement is followed by diarrhea, which may
      be explained, at least in part, to the loss of microvilli and the decreased
      ability of the infected cells to absorb fluids. EPEC also attach to the surfaces
      of a number of cultured cells including CaCo-2, LLC-PK, and PtK2 cells. The
      extracellular, attached EPEC induce filaments of actin to form in the cytoplasm
      just underneath the EPEC surface attachment sites. Beneath some of the attached
      EPEC, the actin filaments become organized into membrane encased columns that
      extend up to 6 micrometers above the cell surface creating "pedestals" on which
      the EPEC rest. The raised pedestals can be readily observed in stereo pairs taken
      using the Intermediate Voltage Electron Microscope. The concentration of non
      muscle isoforms of myosin II and tropomyosin near the base of the pedestals
      suggests a similarity of these structures to brush border microvilli. Video
      microscopy indicates that these EPEC pedestals can bend and undulate, alternately
      growing longer and shorter while remaining tethered in place on the cell surface.
      Some of the attached EPEC also translocate along the cell surface, reaching
      speeds up to 0.07 micrometers/sec. Both types of movement are inhibited by
      cytochalasin D, indicating that actin polymerization in the pedestals is required
      for the motility of EPEC on the host cell surface. In this respect, EPEC motility
      on host cells resembles the intracellular motility of Listeria, but there are
      differences in the actin filament bundles induced by the two different bacteria.
      The most obvious one is the interposition of the cell membrane between EPEC and
      the actin filaments in the pedestal in contrast to the close apposition of actin
      filaments to Listeria. The intensity of fluorescence of rhodamine phalloidin is
      nearly uniform along most of the length of the pedestals indicating a constant
      number of actin filaments, whereas the fluorescence intensity decreases along the
      length of Listeria tails reflecting the disassembly that occurs all along the
      tails. Epec's movements may be a hybrid of Listeria filopodia and Aplysia
      inductopodia movements. This paper is the first report of a microbe attached to
      the extracellular surface of an infected cell propelled by an intracellular actin
      polymerization-dependent mechanism.

PMID- 8871817
TI  - Comparison of the intracellular distribution of cytoplasmic dynein and kinesin in
      cultured cells: motor protein location does not reliably predict function.
AB  - While immunolocalization methods have been used as a reasonable means to judge
      where a given molecule may be active in the cellular milieu, the correlation
      between distribution and function for proteins involved in intracellular
      transport may not be clear cut. To address the question of specificity and
      reproducibility of immunolocalization of microtubule-based motor proteins, we
      have co-localized cytoplasmic dynein and kinesin by immunofluorescence microscopy
      using two specific antibodies for each motor molecule. The results indicate that
      cytoplasmic dynein and kinesin appear to co-localize on a small subset of
      vesicles, but largely reside or accumulate on morphologically distinct
      organelles. In addition, anti-kinesin antibodies differing in their epitope
      specificity label different cellular compartments. To address the question of
      whether the distribution of motor molecules is representative of organelles that
      are undergoing active transport, we have altered the activity of vesicle
      trafficking pathways in fibroblasts using several different methods, including
      cytoplasmic acidification and disruption of cellular compartments with brefeldin
      A, nocodazole and okadaic acid. Analysis of the distribution of cytoplasmic
      dynein and kinesin under these conditions indicates that immunolocalization data
      alone are not reliable indicators of sites of likely function for these
      microtubule-based motors.

PMID- 8871818
TI  - Site-directed mutagenesis enabled preparation of a functional fluorescent analog
      of profilin: biochemical characterization and localization in living cells.
AB  - The preparation of fluorescent profilin analogs for binding and spectroscopic
      studies, in vitro and in vivo, has been hampered by the poor chemical reactivity
      of this protein in its native form. We have addressed this problem by labeling a
      mutant, chemically reactive form of profilin. Site-directed mutagenesis was first
      used to replace a serine residue in a non-essential domain with a reactive
      cysteine residue. The mutant protein was expressed in Escherichia coli and
      reacted with tetramethylrhodamine iodoacetamide. In vitro assays indicated that
      the fluorescent profilin maintained its ability to bind actin, polyproline, and
      PIP2, to inhibit actin polymerization, and to stimulate actin nucleotide
      exchange. Fluorescence spectroscopy showed that neither the excitation nor the
      emission of the analog was sensitive to the interaction with actin or
      polyproline. However, binding of PIP2 caused a 75% quenching of the fluorescent
      signal, suggesting a dramatic change in the immediate environment of the probe.
      When the fluorescent profilin was microinjected into living NRK cells, it became
      localized at cell-cell junctions and discrete sites near the anterior end, where
      it colocalized with aggregates of unpolymerized actin. Different engineered forms
      of profilin with fluorophores located at defined sites should greatly facilitate
      the study of its interactions with various ligands and cellular structures.

PMID- 8871819
TI  - Mechanisms blocking microtubule minus end assembly: evidence for a tubulin dimer
      binding protein.
AB  - We have characterized an activity in sea urchin eggs which prevents microtubule
      assembly at minus ends. Using Chlamydomonas axoneme fragments to nucleate the
      assembly of plus and minus end microtubules, we find robust assembly at
      microtubule plus ends with negligible assembly at minus ends. The minus end
      assembly inhibitor does not co-pellet with microtubules when assembly is
      stimulated with DMSO while the resulting pellet of tubulin and microtubule
      associated proteins readily assembles from both plus and minus ends of axoneme
      fragments. Addition of increasing concentrations of porcine bran tubulin to the
      tubulin and MAP-depleted fraction eventually saturates the minus end inhibitory
      activity. Compared to purified tubulin, cytosolic fractions both increase the
      minus end critical concentration approximately 3 fold and decrease the plus end
      critical concentration. The inhibitory activity is removed by heating, trypsin,
      or by co-immunoprecipitation with tubulin. We hypothesize that a tubulin dimer
      binding protein is responsible for preventing assembly onto minus ends in our in
      vitro assays and speculate that this protein functions in vivo to prevent
      spontaneous nucleation, thus limiting assembly to nucleation sites.

PMID- 8871820
TI  - Identification and quantitation of human chromosomes by primed in situ synthesis.

PMID- 8871821
TI  - Cytogenetic and molecular analysis of the satellite DNA of the genus Ctenomys
      (Rodentia Octodontidae) from Uruguay.
AB  - The genus of subterranean rodents Ctenomys presents the widest range of
      variability in diploid number among mammals (from 2n = 10 to 2n = 70). In
      Uruguay, this variability is observed in karyotypes with 2n = 44, 50 or 58 and
      two geographically isolated populations with 70 chromosomes but different
      karyotypic structure. The last three populations were analyzed in the present
      study. They present a satellite DNA, which was isolated from genomic DNA after
      AluI digestion. In situ hybridization showed that this satellite DNA is located
      in the centromeric region of a few chromosomes, coincident with Hoechst 33258
      staining and C-banding patterns. A similar satellite DNA was detected in
      Argentinian species of this genus. We established that, in spite of differences
      in number of positive heterochromatic blocks per karyotype, the C value is the
      same in the three populations studied. The nature and possible evolutionary path
      of this repeated DNA is discussed.

PMID- 8871822
TI  - Evidence for a sequence-directed conformation periodicity in the genomic highly
      repetitive DNA detectable with single-strand-specific chemical probe potassium
      permanganate.
AB  - A single-strand-specific chemical probe, potassium permanganate (KMnO4), was used
      to study the sequence-dependent conformation periodicity of tandem multicopy
      repetitive DNA sequences HRS60 and GRS (Nicotiana Species) at the level of single
      base pair and dinucleotide step. Local DNA structures, sensitive to KMnO4,
      revealed periodicity of 182 +/- 2 bp, equal to the length of repeat units.
      Permanganate-sensitive local structures were mapped to both DNA strands of
      genomic HRS60 sequences and were found to be linked to d(A)n tracts. These
      adenine tracts are located in the proximity of the intrinsically curved domains.
      Distamycin A increased reactivity of the DNA but decreased the specificity of DNA
      cleavage. Similar conformation periodicity has been detected also in the 'canrep'
      family of repeats (Brassica species). All studied repetitive sequences are
      predominantly located in the constitutive heterochromatin. We discuss the role of
      conformation periodicities in relation to a structural code for nucleosome
      phasing at tandem arrays of DNA repeats.

PMID- 8871823
TI  - Meiotic behavior of the X1X2Y1Y2 quadrivalent of the primate Alouatta caraya.
AB  - A multiple sex chromosome system was found in three unrelated individuals of the
      primate Alouatta caraya. This mechanism is originated by a translocation between
      the Y chromosome and one of the autosomes (A7). Mitotic karyotypes show two
      small, acrocentric chromosomes (AY and YA), which are the translocation products.
      In metaphase I of male meiosis, there is a very long chain quadrivalent in which
      the order of the element is: X-YA-A7-AY. Segregation in the quadrivalent is
      alternate and gives balanced products. Synaptonemal complex karyotypes at
      pachytene show the structure of the quadrivalent made by the four axes. There is
      a slight difference in the relative length of AY and YA and the kinetochore of A7
      aligns with that of AY. The synaptic pattern and changes in the quadrivalent
      during pachytene are described. Thin sections of the quadrivalent body show that
      the chromatin packing in the sex chromosome region is different from that of the
      autosomal region. This X1X2Y1Y2/X1X1XX2 sex chromosome system may be extended
      among other members of the genus Alouatta.

PMID- 8871824
TI  - The Ty1-copia group retrotransposons of Allium cepa are distributed throughout
      the chromosomes but are enriched in the terminal heterochromatin.
AB  - The genomic organization and diversity of the Ty1-copia group retrotransposons
      has been investigated in a monocotyledonous plant, Allium cepa. We used the
      polymerase chain reaction (PCR) to generate sequences corresponding to a
      conserved domain of the reverse transcriptase gene of Ty1-copia retrotransposons
      in this plant. Sequence analysis of 27 of these PCR products shows that they are
      a highly heterogeneous population, a feature which is common in plants but not in
      yeast and Drosophila. Slot-blot analysis shows there are 100,000-200,000 copies
      of Ty1-copia group retrotransposons within the A. cepa genome (2C = 31.7 pg),
      indicating that they are a significant component of the genome of this plant. In
      situ hybridization to metaphase chromosomes reveals that Ty1-copia
      retrotransposons are distributed throughout the euchromatin of all chromosomes of
      A. cepa but are enriched in the terminal heterochromatic regions, which contain
      tandem arrays of satellite sequences. This is the first clear evidence for the
      presence of Ty1-copia retrotransposons in the terminal heterochromatin of plants
      and contrasts with the distribution of these elements in other plant species.

PMID- 8871825
TI  - Genomic instability in MycER-activated Rat1A-MycER cells.
AB  - The deregulated expression of c-Myc protein is associated with the non-random
      locus-specific amplification of the dihydrofolate reductase (DHFR) gene. This
      study was performed to determine whether additional chromosomal aberrations occur
      when c-Myc protein levels are up-regulated for prolonged periods. To this end, we
      have used Rat1A-MycER cells, which allow the experimental regulation of Myc
      protein levels. We examined the genomic stability of Rat1A-MycER cells cultivated
      in either the absence or the presence of estrogen, which reportedly activates the
      chimeric MycER protein in these cells. Following prolonged periods of MycER
      activation, Rat1A-Mycer cells exhibited irreversible chromosomal aberrations. The
      aberrations included numerical changes, chromosome breakage, the formation of
      circular chromosomal structures, chromosome fusions, and extrachromosomal
      elements.

PMID- 8871826
TI  - Autosomal location of a new subtype of 1.688 satellite DNA of Drosophila
      melanogaster.
AB  - During the screening of a Drosophila melanogaster YAC library with DNA from the
      minichromosome Dp(1;f)1187 we isolated a clone, yw20D5, which contains a new
      subtype of 1.688 satellite DNA. Although the sequences of several monomers
      subcloned from the YAC show a considerable variation in length, the derived
      consensus sequence is 356-bp long. This new subtype and the one constituted by
      the 353-bp repeats are both located on the left arm heterochromatin of chromosome
      3, arranged in separate arrays. Despite their autosomal location, phylogenetic
      relationships among 1.688 satellite sequences suggest that they may have
      originated from the 359-bp repeats of the X chromosome heterochromatin. We have
      used the new 356-bp repeats to investigate whether sequences related to the 1.688
      satellite are dispersed along the euchromatic arms of the autosomes in a similar
      way to that in which they are found along the X chromosome euchromatin.

PMID- 8871827
TI  - Redistribution of ribosomal DNA after blocking of transcription induced by
      actinomycin D.
AB  - We report on the effect of different doses and times of incubation of the
      cytostatic drug actinomycin D (AMD) on nucleolar morphology, rRNA gene
      transcription and rDNA gene localization using in situ hybridization and the
      immunocytochemical detection of the human upstream binding factor (UBF) at the
      electron microscopic level in HeLa cells. Low doses of AMD (0.001 micrograms/ml,
      30 min) selectively block rRNA gene transcription but alter neither nucleolar
      morphology nor the localization of rDNA with respect to the nucleolar components.
      Treatment with high doses of AMD (0.05 micrograms/ml, 1 h) resulted in a
      retraction of the rDNA out of the nucleolus in addition to the well-known
      blocking of rDNA transcription, total nuclear transcription and nucleolar
      segregation. Under these conditions accumulations of rDNA were found in patches
      of chromatin at the nucleolar periphery. We conclude that the blocking of rRNA
      gene transcription and the changes in nucleolar morphology, both induced by AMD
      at different doses, are independent phenomena.

PMID- 8871828
TI  - Chromosomal localization of a highly repeated EcoRI DNA fragment in Megoura
      viciae (Homoptera, Aphididae) by nick translation and fluorescence in situ
      hybridization.
AB  - To investigate the genome of the aphid Megoura viciae at molecular level, we have
      studied total DNA by agarose gel electrophoresis after cleavage with different
      restriction endonucleases. EcoRI digestion produced a highly repeated DNA
      fragment, about 600 pb long. The contribution of this EcoRI element to the total
      genome of M. viciae was estimated at about 6% by means of densitometric scanning
      of agarose gel photographs. The chromosomal localization of this fragment,
      investigated by fluorescent in situ hybridization (FISH), constantly showed one
      large and two narrower fluorescent bands located on the X chromosome, all
      corresponding to C-positive heterochromatic areas. These results are in full
      accordance with the data obtained by in situ nick translation experiments carried
      out after EcoRI digestion, and clearly demonstrate that a substantial amount of
      M. viciae heterochromatin consists of EcoRI fragments which are mainly located on
      the X chromosome. Using the EcoRI restriction fragment as a molecular probe may
      be a practical tool for the investigation of taxonomic and evolutionary
      relationships in this group of insects.

PMID- 8871829
TI  - Rapid isolation of recombinant lambda phage DNA for use in fluorescence in situ
      hybridization.

PMID- 8871830
TI  - A cytogenetic analysis of rye introgression into a Portuguese bread wheat
      cultivar Barbela.

PMID- 8871831
TI  - Direct chromosome mapping of plant genes by in situ polymerase chain reaction (in
      situ PCR).

PMID- 8871832
TI  - The case-control study and its potential biases.

PMID- 8871833
TI  - Superantigens and experimental SLE induced by idiotypic dysregulation.
AB  - OBJECTIVE: The effects of the superantigens (SAgs) Staphylococcal Enterotoxin B
      (SEB), Toxic Shock Syndrome Toxin-1 (TSST-1) and Mycoplasma Arthritidis Mitogen
      (MAM) were examined on the induction and on the course of experimental SLE-like
      disease. METHODS: Immunization of BALB/c mice with human anti-DNA mAb (MIV-7)
      carrying the pathogenic idiotype 16/6 emulsified in complete Freund's adjuvant
      (CFA), followed by a boost of MIV-7/PBS 3 weeks later, generated an experimental
      SLE via an idiotypic dysregulation. RESULTS: After immunization with MIV-7/SAg,
      replacing the MIV-7 boost by SAg, and then injecting SAg 7 weeks after the
      regular induction of the SLE-like disease, the mice failed to produce anti-hIgM
      and dsDNA Ab up to 6 months after the induction. The mice immunized with MIV
      7/CFA and boosted with the SAg had high titers of anti-hIgM but no detectable
      anti-dsDNA Ab. In both experimental groups low titers of anti-CL Abs developed in
      25/40 (62%) and 30/38 (79%) of the mice respectively, including the control mice
      immunized with non-pathogenic human IgM/SAg or PBS/SAg. The mice immunized
      according to the "classical" protocol showed increased titers of anti-dsDNA Ab
      (22%) and anti-CL Ab (28%) during 10 weeks of observation. In contrast SEB, TSST
      1 and MAM induced a 29%, 1% and 17% reduction in the anti-DNA titers and a 32%,
      15% and 12% reduction in the anti-CL titers, respectively. CONCLUSIONS: These
      data suggest that the SAg tested here cannot replace the effect of CFA in the
      induction of the primary humoral response. The SAgs TSST-1, SEB and MAM did not
      induce the SLE-like disease following idiotypic modulation. Moreover, they may
      have had a suppressive effect on the idiotypic network in our model. The
      appearance of anti-CL Abs in almost all the experimental groups including the
      naive mice supports the possibility that microbial SAgs can induce the production
      of autoantibodies by different mechanisms. The SAgs TSST-1, SEB and MAM reduced
      autoantibody production in the serologically established idiotypic-induced
      experimental SLE-like murine model. This beneficial effect may indicate new
      directions for research on the management of SLE.

PMID- 8871834
TI  - Interferon alpha-2 (IFN alpha 2) increases lacrimal and salivary function in
      Sjogren's syndrome patients. Preliminary results of an open pilot trial versus OH
      chloroquine.
AB  - OBJECTIVE: The effect of recombinant interferon alpha-2 (IFN alpha 2) therapy in
      Sjogren's syndrome (SS) was studied. METHODS: An open study was performed in
      which 20 SS patients were given IFN alpha 2 3.10(6) MU/3 times/week or OH
      chloroquine (OH-C) 6 mg/kg/daily, for a mean period of 11 months. RESULTS: Gland
      assessment showed that lacrimal and salivary function improved by 67% and 61%
      versus 15% and 18% respectively (p < 0.01) in the patients treated with IFN alpha
      2 compared to those treated with OH-C. Immunological parameters did not change
      over time in either group. In 3 patients a decrease in the tissue score was
      observed in the IFN alpha 2 group, while no changes were seen in the control
      group. Tolerability was acceptable. CONCLUSION: This study shows that IFN can
      improve tear function and dry mouth in SS, without causing significant side
      effects.

PMID- 8871835
TI  - Cardiac manifestations in dermato-polymyositis.
AB  - OBJECTIVE: To describe the functional and anatomic heart abnormalities of
      patients with dermato-polymyositis. METHODS: Thirty-two consecutive patients with
      dermato-polymyositis (DM/PM) were studied. Patient assessments included a
      questionnaire for cardiac symptoms, physical examination, muscular enzymes,
      standard electrocardiogram (EKG), chest radiographs, spirometry, Holter
      monitoring and color Doppler flow (CDF) studies. Features evaluated with CDF
      included left ventricular diastolic dysfunction (LVDD), hyperdynamic heart,
      mitral valve prolapse, and endomyocardial fibrosis. RESULTS: Twenty-five patients
      (78%) were female. The mean age was 43 years and the mean disease duration 6
      years. Twenty-six (81%) patients had dermatomyositis. Only 2 (6%) had cardiac
      symptoms. Spirometry was performed in 20 patients, Holter monitoring in 23 and
      CDF in 26 patients. Electrical disturbances detected by either EKG or Holter were
      present in more than half of the patients studied. LVDD was identified in 11
      patients (42%) and hyperdynamic heart in 4 (15%). None of the 26 patients studied
      by CDF had mitral valve prolapse. No significant differences in the frequency of
      cardiac abnormalities, including LVDD, were observed in relation to the diagnosis
      of DM or PM, the presence of Raynaud's phenomenon or calcinosis, or the disease
      activity status at the moment of the study. CONCLUSIONS: Subclinical heart
      abnormalities are frequent in patients with DM/PM. LVDD appears to be common. Our
      findings suggest that cardial assessment of patients should be performed in order
      to detect abnormalities requiring specific therapy.

PMID- 8871836
TI  - Low serum hyaluronan in psoriatic arthritis patients in comparison to rheumatoid
      arthritis patients.
AB  - OBJECTIVE: Serum hyaluronan (HA) was determined in 37 patients suffering from
      psoriatic arthritis (PSA), 39 patients with rheumatoid arthritis (RA), 31 with
      osteoarthritic joint disease (OA) and 26 healthy controls (C) in order to examine
      earlier reports that HA levels are increased in the serum of RA and to assess
      whether this finding is also relevant for PSA, another inflammatory joint
      disease, since HA in serum is considered a sign of inflammation in general.
      METHOD: HA in the serum samples was measured with an enzyme linked microplate
      assay. RESULTS: Sera from PSA, RA and OA patients showed a significantly higher
      HA concentration than those of healthy controls (56.0 +/- 16.0 micrograms/l). The
      serum HA concentration in PSA patients amounted to 107.8 +/- 57.2 micrograms/l,
      which was not significantly different from OA patients (104.9 +/- 16
      micrograms/l). A significant difference, however, could be observed between the
      HA concentrations of the PSA subgroups: the mean HA level of patients suffering
      from symmetrical polyarthritis was 134 +/- 79.6 micrograms/l, which turned out to
      be significantly higher than in patients suffering from symmetrical
      oligoarthritis (89.9 +/- 42.8 micrograms/l; P < 0.04), but was insignificantly
      increased in comparison to patients with ankylosing spondylitis as the
      predominant feature (109 +/- 27.8 micrograms/l; P = 0.49). The mean HA
      concentration for RA sera was 197.1 +/- 122.9 micrograms/l, which was
      statistically significantly increased compared to PSA (P < 0.001) and OA (P <
      0.001) sera. The sera of seropositive RA patients showed significantly higher HA
      levels than PSA patients with symmetrical polyarthritis (P < 0.04). CONCLUSION:
      The data obtained support recent studies which have shown HA levels to be higher
      in RA patients than in OA patients. Seronegative and seropositive RA patients
      showed the same HA concentrations, while patients suffering from "seronegative"
      PSA were found to have lower HA concentrations. Therefore, HA serum levels may
      reflect cartilage degradation in general or the degree of articular inflammatory
      processes, indicating different pathogenetic pathways.

PMID- 8871837
TI  - The releasability of lysosomal enzymes from neutrophil leukocytes in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To study the enzyme content and the "releasability" of lysosomal
      enzymes (lysozyme and beta-glucuronidase) in neutrophils purified from peripheral
      blood of patients with rheumatoid arthritis (RA) or normal subjects. METHODS:
      Neutrophils were obtained from 13 patients (10 women and 3 men) with rheumatoid
      arthritis and from 11 healthy subjects (8 women and 3 men). We measured: (1)
      lysosomal enzyme (lysozyme and beta-glucuronidase) content; (2) spontaneous
      enzyme release; (3) lysosomal enzyme release after cell challenge with different
      segretagogues (FMLP, C5a, aggregated IgG, zymosan and Ca2+ ionophore A23187).
      RESULTS: The lysosomal enzyme content was not statistically different in control
      subjects and in patients with RA (7.4 +/- 1.9 vs 6.3 +/- 0.8 micrograms/10(6)
      neutrophils for lysozyme; 102.9 +/- 16.4 vs 78.9 +/- 11.2 micrograms/10(6)
      neutrophils for beta-glucuronidase in control and RA subjects, respectively, p =
      NS). Unstimulated release of lysozyme was significantly lower in RA patients (3.8
      +/- 1.1%) when compared to control subjects (9.5 +/- 2.1%) (p < 0.05). In
      contrast, spontaneous release of beta-glucuronidase did not differ in the two
      groups (5.5 +/- 0.9% and 3.8 +/- 1.1% in control and RA subjects, respectively).
      Enzyme release induced by FMLP (3 x 10(-9)-3 x 10(-7) M), C5a (10(-8)-10(-7) M),
      aggregated IgG (0.1-0.6 mg/ml), or Ca2+ ionophore A23187 (0.1-1 microgram/ml) did
      not differ statistically in the two groups of subjects. Neutrophil stimulation by
      serum-treated zymosan, at the concentration of 0.3 mg/ml, induced a release of
      lysozyme that was significantly higher in patients with RA when compared to
      control subjects (p < 0.05), whereas zymosan-activated beta-glucuronidase
      secretion was similar in the two donor populations. CONCLUSIONS: This study
      suggests that the contribution of leukocytes to the inflammatory processes
      typical of RA does not depend on an altered "releasability" of preformed
      mediators from peripheral blood neutrophils.

PMID- 8871838
TI  - In vitro effects of methotrexate on polyamine levels in lymphocytes from
      rheumatoid arthritis patients.
AB  - OBJECTIVE: Several studies have documented increased levels of polyamines in
      rheumatoid arthritis (RA). We have suggested that one of the mechanisms of action
      of methotrexate (MTX) involves the inhibition of polyamine synthesis in
      lymphocytes. In this study, we sought to establish the inhibitory effect of MTX
      on polyamine synthesis and its specificity. METHODS: Polyamine levels were
      determined in stimulated RA lymphocytes incubated in vitro with MTX and compared
      to levels in lymphocytes incubated with hydrocortisone, D-penicillamine, or
      medium alone. Lymphocyte polyamine levels were correlated with IgM-rheumatoid
      factor (RF) synthesis. RESULTS: Incubation with MTX resulted in concentration
      dependent decreased intracellular levels of spermidine and spermine, while
      putrescine levels were not affected. Addition of folinic acid or S-adenosyl
      methionine (SAM) prevented this MTX-induced inhibition. Incubation with D
      penicillamine or hydrocortisone had no significant effect on polyamine levels.
      There was a positive correlation between intracellular polyamine levels and the
      inhibition of IgM-RF synthesis by MTX. CONCLUSION: These data suggest that MTX
      inhibits the synthesis of spermidine and spermine in stimulated RA lymphocytes
      through inhibition of the SAM-dependent pathway. This inhibition may be related
      to the immune-modulating properties of MTX.

PMID- 8871839
TI  - Association of methotrexate and corticosteroids in the treatment of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether the association of methotrexate (MTX) and
      corticosteroids introduced concomitantly is more effective than MTX alone in
      patients with rheumatoid arthritis (RA). METHODS: Twenty-eight RA patients (group
      1) were treated with MTX (mean dose: 10 +/- 1.4 mg/week) and corticosteroids
      (mean dose: 14.9 +/- 5.6 mg/day, range: 5-25) introduced concomitantly, and were
      compared to 251 RA patients (group 2) treated with MTX alone (mean dose: 9.8 +/
      1.5 mg/week). Variations in the clinical (number of swollen and painful joints,
      morning stiffness, Ritchie's articular index), biological (ESR, CRP), and
      radiological parameters were studied. Remission was defined according to Pinals'
      criteria. At baseline, there were no significant differences between the two
      groups, except for a greater number of swollen and painful joints in group 1 (p =
      0.03 and p = 0.01, respectively). The total MTX dose and the duration of
      treatment (26 +/- 21.8 months in group 1 versus 33.5 +/- 27.2) months in group 2)
      did not differ between the two groups. RESULTS: We noted a more marked reduction
      in the number of swollen and the number of painful joints in group 1 (p = 0.03).
      No differences were noted for the other clinical and biological parameters. The
      proportion of patients fulfilling Pinals' remission criteria was higher in group
      1 (25% versus 10.1% in group 2, p = 0.04). The steroid dosage could be
      significantly reduced in group 1 (-3.4 +/- 6.1 mg/day, p = 0.05) and
      corticosteroids were stopped in 11 patients. The frequency and type of side
      effects, as well as the frequency and reasons leading to MTX withdrawal, did not
      significantly differ between the two groups. CONCLUSION: The association of MTX
      and corticosteroids seems to bring about a greater improvement in the different
      clinical activity parameters of RA than MTX alone, without any significant
      increase in the frequency of side effects. These results need to be confirmed in
      larger scale prospective studies.

PMID- 8871840
TI  - Increased prevalence of joint manifestations in patients with recurrent aphthous
      stomatitis (RAS)
AB  - OBJECTIVE: To characterize the systemic manifestations and joint disease in
      patents with recurrent aphthous stomatitis (RAS). METHODS: The presence and
      features of extra-oral manifestations were determined by a rheumatologist, who
      examined and interviewed 64 patients, referred during 1993 to the oral medicine
      clinic for treatment of RAS. Controls were 65 medical staff members of a military
      clinic associated with the hospital. RESULTS: Based on the rheumatologist's
      findings and published criteria, the patients were diagnosed as suffering from
      RAS alone (24 patients), Reiter's syndrome (8), Behcet disease (8), familial
      Mediterranean fever (1), or RAS with undiagnosable extra oral manifestations
      (23). Thirteen patients in the last group had joint disease (p < 0.01 compared to
      the controls), characterized by recurrent mono- or oligoarthritis/arthralgia of
      short duration, affecting mostly the large joints. Conjunctivitis, pustular rash,
      lower back pain and urethritis/cervicitis were also common in RAS patients, but
      only the latter was significantly more frequent in RAS patients than in controls
      (p < 0.02). CONCLUSION: These findings suggest that patients with RAS have an
      increased frequency of a palindromic type joint disease.

PMID- 8871841
TI  - Interleukin-6 and soluble interleukin-2-receptor in psoriatic arthritis:
      correlations with clinical and laboratory parameters.
AB  - OBJECTIVE: In this study we evaluated the relationships of IL-6 and sIL-2R levels
      with the main clinical and laboratory parameters in PsA patients with peripheral
      polyarthritis. METHODS: Serum levels of IL-6 and sIL-2R were measured by an
      enzyme immunoassay kit in patients with peripheral (< 4 joints) PsA (n = 47),
      with RA (n = 41), or with psoriasis (N = 15) and in healthy volunteers (n = 15)
      RESULTS: The patients with PsA had higher serum levels of IL-6 and sIL-2R than
      healthy volunteers and psoriatic patients, while they showed lower levels of IL-6
      and sIL-2R than RA patients. We found abnormal values for IL-6 and sIL-2R in
      63.8% and 57.4% of PsA patients, respectively. IL-6 levels correlated with the
      number of painful and swollen joints, RAI, physician's assessment, CRP and ESR,
      while sIL-2R levels correlated only with the number of swollen joints, the
      physician's assessment and ESR. IL-6 and sIL-2R correlated with each other.
      CONCLUSION: Our study shows that IL-6 and sIL-2R may play a role in the
      pathogenetic mechanism of psoriatic arthritis.

PMID- 8871842
TI  - Reflex sympathetic dystrophy syndrome following acute gouty arthritis.
AB  - The unusual case of reflex sympathetic dystrophy syndrome caused by an acute
      attack of gout is reported. The syndrome, involving the left ankle and hindfoot,
      developed twelve days after a classical gouty attack involving the first
      metatarso-phalangeal joint of the same foot. Diagnosis was based on X-ray and
      scintigraphic and MRI changes A prompt clinical remission was achieved with a
      short course of i.v. clodronate.

PMID- 8871844
TI  - The cross-reactivity of autoantibodies in connective tissue diseases.
AB  - This paper analyses various factors involved in the determination of the cross
      reactivity of autoantibodies in connective tissue diseases. We report the results
      of various studies of antigens and antibodies relating to this topic, and
      consider the possible role of cross-reactivity in the pathogenesis of some of the
      clinical manifestations of systemic autoimmune diseases.

PMID- 8871843
TI  - Acute estrogen administration can reverse cold-induced coronary Raynaud's
      phenomenon in systemic sclerosis.
AB  - A 52-year-old postmenopausal woman with long-standing progressive systemic
      sclerosis and Raynaud's phenomenon was examined by dipyridamole-thallium-201
      myocardial imaging and cold pressor thallium-201 myocardial scintigraphy. The
      dipyridamole test revealed normal myocardial perfusion, while the cold pressor
      test showed reversible ischemia to the anteroapical myocardial wall, indicating
      coronary Raynaud's phenomenon. Acute intravenous administration of conjugated
      estrogens led to normalization of the cold-induced thallium-201 defect. This is
      the first reported case of the beneficial effect of estrogens in coronary
      Raynaud's phenomenon.

PMID- 8871845
TI  - Vitamin E, thiobarbituric acid reactive substance concentrations and superoxide
      dismutase activity in the blood of children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To study the role of active oxygen species in tissue injury in
      rheumatoid arthritis. METHODS: We examined the levels of thiobarbituric acid
      reactive substances (TBARS) and antioxidants of the first line antioxidative
      defence of the organism, i.e. vitamin E (VE) and superoxide dismutase (SOD) in
      the blood of 74 young patients with juvenile rheumatoid arthritis (JRA) and in
      138 healthy children, all aged 3-15. RESULTS: A statistically significant
      increase of TBARS was found in the blood plasma of the children with JRA compared
      with the control group. In the whole group of patients and in the patients over 6
      years of age, the VE concentration was in the red blood cells (RBC) was
      significantly lower in children who had suffered from JRA for more than one year
      and in those with the systemic form of the disease. The type of treatment also
      affected the values for the plasma VE and SOD in the RBC. CONCLUSION: Our results
      seem to confirm the supposition of increased oxidative stress in children with
      JRA and low antioxidant levels in terms of SOD activity and vitamin E
      concentrations.

PMID- 8871846
TI  - Incidence of chronic juvenile rheumatic diseases in Finland during 1980-1990.
AB  - OBJECTIVE: To study trends in the incidence of juvenile rheumatoid arthritis
      (JRA) and to obtain information on the incidence of other juvenile rheumatic
      diseases in Finland. METHODS: The present study covered those subjects entitled
      under the nationwide sickness insurance scheme to receive specially reimbursed
      medication for juvenile rheumatic diseases in 5/21 central hospital districts in
      Finland (population base about 270,000 children < 16 years of age) in 1980, 1985
      and 1990. RESULTS: A total of 114 incident cases (34 boys, 80 girls) satisfied
      the criteria for JRA during the three study years: 1980, 1985 and 1990. Seven of
      the patients had systemic-onset disease. The incidence of JRA remained similar
      (14/100,000 in the population < 16 years of age). The female: male ratio was 2.4:
      1. Only one case of juvenile spondyloarthropathy was found. Seven patients had
      juvenile systemic lupus erythematosus and four had juvenile dermato/polymyositis.
      The corresponding annual incidence rates were 0.1, 0.9 and 0.5/100,000,
      respectively, in this population. CONCLUSION: The present study provides
      population-based figures on the occurrence of various chronic arthritic syndromes
      in childhood using a unified data base. The incidence of JRA remained quite
      similar for the three study years. The incidence figures for systemic rheumatic
      and connective tissue diseases were slightly higher than those reported in
      previous studies.

PMID- 8871847
TI  - An unusual chronic monooarticular synovitis of the right distal radioulnar joint.

PMID- 8871848
TI  - Morphea and rheumatoid arthritis.

PMID- 8871849
TI  - Steroid induced avascular necrosis of the patella in an ulcerative colitis
      patient.

PMID- 8871850
TI  - Juvenile rheumatoid arthritis, Crohn's disease and Turner's syndrome: a novel
      association.

PMID- 8871851
TI  - Atypical methotrexate dermatitis in a patient with rheumatoid arthritis.

PMID- 8871852
TI  - New nomogram for lamellar keratoplasty for hyperopia.

PMID- 8871853
TI  - Refractive aniseikonia: a source of binocular vision stress and asthenopia.

PMID- 8871854
TI  - Excimer laser system failure.

PMID- 8871855
TI  - Vision-threatening stromal folds after myopic keratomileusis.

PMID- 8871856
TI  - FDA writes warning letter to users of homemade and illegally imported lasers.

PMID- 8871857
TI  - Regulatory considerations regarding the use of the excimer laser for LASIK.

PMID- 8871858
TI  - Laser in situ keratomileusis to correct myopia of -6.00 to -29.00 diopters.
AB  - BACKGROUND: Photorefractive keratectomy can cause corneal scarring and visual
      loss in highly myopic eyes. We evaluated laser in situ keratomileusis (LASIK)
      because it has the theoretical advantage of preserving both the corneal
      epithelium and Bowman's layer. METHODS: In a prospective study, LASIK was
      performed in 62 myopic eyes (42 patients) using the Automatic Corneal Shaper
      (Chiron Vision) and the Keracor 116 excimer laser (Chiron Technolas). We measured
      refraction and visual acuity, and evaluated corneal topography (TMS 1) and
      corneal clarity after 4 to 8 weeks and 4 to 6 months. RESULTS: Four- to 6-month
      follow up was completed in 51 eyes. The mean preoperative spherical equivalent
      refraction was -14.80 diopters (D) (range, -6.00 to -29.00 D). Postoperatively,
      the mean deviation from the target refraction was -1.70 D (range, -9.00 to +2.50
      D) at 4 to 8 weeks and -1.90 D (range, -9.50 to +2.25 D) at 4 to 6 months. At 4
      to 6 months, 19 eyes (37%) were within +/- 0.50 D of the target refraction, 24
      (47%) within +/- 1.00 D, 33 (65%) within +/- 2.00 D, and 40 (78%) within +/- 3.00
      D. From 4 to 8 weeks to 4 to 6 months, the mean regression of myopia was -0.20 D
      (0.50 D or less in 24 eyes [47%], 1.00 D or less in 32 [63%], and 2.00 D or less
      in 42 [82%]). In six eyes (12%), the stromal interface was not visible, in 38
      (74%) it was barely visible, and in seven (14%) it was clearly visible. Corneal
      topography revealed only small variations in clear-zone size and dioptric value,
      demonstrating a very stable correction 4 to 6 months postoperatively.
      CONCLUSIONS: LASIK may be a safe and effective procedure to correct high myopia.
      Further research is required to develop satisfactory microkeratome technology,
      effective laser algorithms, and to determine long-term stability of refraction.

PMID- 8871859
TI  - Comparison of intersecting trapezoidal keratotomy and arcuate transverse
      keratotomy in the correction of high astigmatism.
AB  - BACKGROUND: High astigmatism can be corrected using trapezoidal or arcuate
      transverse keratotomies. Videokeratography enables qualitative evaluation of the
      corneal topography. METHODS: Fifty-five eyes of 41 patients presenting with high
      astigmatism after penetrating keratoplasty or naturally occurring astigmatism
      (mean, 6.29 diopters [D]; range, 3.00 to 16.00 D) underwent correction using
      either intersecting trapezoidal or arcuate transverse keratotomies. Corneal
      topographic maps were analyzed and classified into keratographic patterns. Mean
      follow up was 3 years (range, 1 to 6 years). RESULTS: The mean net decrease in
      refractive astigmatism was 3.60 D (52.7% reduction). The flattening/steepening
      ratio was on average higher for intersecting trapezoidal keratotomy (7.26 for
      astigmatism after penetrating keratoplasty and 8.31 for naturally occurring
      astigmatism) than for arcuate transverse keratotomy (.98 in astigmatism after
      penetrating keratoplasty and 1.76 in naturally occurring astigmatism).
      Accordingly, intersecting trapezoidal keratotomy tended to produce a hyperopic
      shift in the spherical equivalent refraction (mean hyperopic shift, 2.65 and .56
      D, respectively). The mean vector-corrected change of refractive astigmatism
      after intersecting trapezoidal keratotomy was 88.8% in naturally occurring (n =
      21 eyes) and 70.3% in penetrating keratoplasty astigmatism (n = 13). Arcuate
      transverse incisions corrected on average 79.9% of naturally occurring (n = 13)
      and 60.8% of penetrating keratoplasty astigmatism (n = 8). Videokeratography
      showed the asymmetric bowtie pattern as the most frequent pattern for both
      procedures. Intersecting trapezoidal keratotomy was characterized by relatively
      higher incidences of polygonal and irregular patterns. Arcuate transverse
      incisions caused less wound healing defects and glare than intersecting
      trapezoidal keratotomy. CONCLUSIONS: Both intersecting trapezoidal keratotomy and
      arcuate transverse incisions effectively reduced high naturally occurring
      astigmatism and astigmatism after penetrating keratoplasty. However, greater
      corneal surface irregularity and more complications were seen following
      intersecting trapezoidal keratotomy. Trapezoidal keratotomy should not be used
      unless a large decrease of myopia is needed, and then a nonintersecting technique
      is preferable.

PMID- 8871860
TI  - Measurement of irregular astigmatism using semimeridian data from
      videokeratographs.
AB  - BACKGROUND: Irregular astigmatism is one of the most troublesome side effects of
      corneal surgery. We attempted to quantify irregular astigmatism in a simple way,
      using semimeridian data from videokeratographs of corneas with different amounts
      of irregular astigmatism. METHODS: We studied the corneal topography of 30 normal
      corneas to be used as controls, 30 corneas from patients after radial keratotomy,
      30 corneas from patients after nonfreeze myopic keratomileusis, and 30 corneas
      with clinically apparent keratoconus. We developed two diagnostic formulas, a
      refractive power symmetry index and an angle symmetry index, using the absolute
      scale, color-coded map, and semimeridian data from the EyeSys Corneal Analysis
      System, and used them to compare the four groups of corneas. RESULTS: In the
      corneas with irregular astigmatism, values for the refractive power symmetry
      index and angle symmetry index were significantly higher than in the normal
      corneas. The refractive power symmetry index confidence interval set at 95% was
      0.58 diopters (D) (range 0.00 D to 0.58 D) in the control group. Using these
      limits, most values in the radial keratotomy, keratomileusis, and keratoconus
      groups were abnormal. Spectacle-corrected visual acuity correlated negatively
      with the refractive power symmetry index (rs = -0.58, p < .001). The refractive
      power symmetry index sensitivity and specificity were respectively 97% and 66%.
      Spectacle-corrected visual acuity did not correlate with the angle symmetry
      index. CONCLUSIONS: Semimeridian data from videokeratographs can be used to
      quantify irregular astigmatism.

PMID- 8871861
TI  - Failure of mechanical epithelial removal to reverse persistent hyperopia after
      photorefractive keratectomy.
AB  - BACKGROUND: Residual hyperopic overcorrection after photorefractive keratectomy
      (PRK) using early algorithms is a rare but serious complication. Anecdotal
      evidence suggests that epithelial removal can stimulate epithelial hyperplasia,
      thereby reducing overcorrection. The aim of this study was to determine if
      epithelial removal effectively reduced hyperopia after PRK for myopia and,
      concurrently, to correlate the healing response with the refractive outcome.
      METHODS: Enrolled were seven eyes of seven patients (mean age, 44 +/- 13 years)
      who had undergone PRK with a mean manifest refractive error of +2.21 +/- 0.74
      diopters (D). All had undergone PRK an average of 24 +/- 9 months previously.
      Epithelial removal was performed over the excimer-treated zone with a surgical
      blade. Subjective refraction, epithelial thickness, corneal topography, and
      subepithelial haze were measured up to 1 year postoperatively. RESULTS: Reduction
      in hyperopia between the baseline and 1-year visit was not statistically
      significant (mean difference, 0.55 D reduction; p = .102). That epithelial
      removal did not stimulate a wound-healing response is further supported by the
      absence of change in epithelial thickness over the first month and the small
      amounts of subepithelial haze. Central corneal power was reduced by a mean of
      0.64 D after 1 month (p < .05). CONCLUSIONS: Epithelial removal alone did not
      reduce the hyperopic overcorrection present after PRK, nor did it stimulate
      epithelial hyperplasia in the majority of these eyes. However, a trend toward
      improvement was noted with time was noted.

PMID- 8871862
TI  - Ultrastructure of picosecond laser intrastromal photodisruption.
AB  - PURPOSE: To investigate the ultrastructure of the corneal stroma after picosecond
      intrastromal photodisruption with a neodymium-doped yttrium-lithium-fluoride
      (Nd:YLF) laser. METHODS: We performed picosecond intrastromal photodisruption on
      six human eye-bank eyes using a lamellar technique. Thirty picosecond pulses at
      1000 Hz and 20 to 25 mJ per pulse were placed in an expanding spiral pattern, the
      pulses separated by 15 microns. Three layers were placed in the anterior stroma,
      separated from each other by 15 microns. In addition, intrastromal radial and
      arcuate incisions were generated in two living rabbit eyes in a plane
      perpendicular to the corneal surface. After the procedure, the corneas were
      processed for scanning and transmission electron microscopy. RESULTS: Scanning
      electron microscopy of the eye-bank eyes demonstrated multiple, coalescing
      intrastromal cavities forming a layer oriented parallel to the corneal surface.
      These cavities had smooth inner walls. Transmission electron microscopy
      demonstrated tissue loss surrounding some cavities, with the terminated ends of
      collagen fibrils clearly evident. Other cavities were formed by separation of
      lamellae, with little evidence of tissue loss. A pseudomembrane was present along
      the margin of some cavities. Although there was occasional underlying tissue
      disruption along the border of a cavity, there was no evidence of thermal damage
      or tissue necrosis. The perpendicular photodisruptions demonstrated intrastromal
      cleavage of corneal collagen similar to diamond-knife incisions, with the
      exception of intact overlying Bowman's and epithelial layers. CONCLUSION:
      Intrastromal photodisruption with a Nd:YLF picosecond laser induced no thermal
      necrosis or coagulative change in the region of tissue interaction. Lamellar
      intrastromal photodisruption demonstrated both tissue loss and lamellar
      separation when performed with the current treatment parameters, possibly
      limiting ablation efficiency and predictability.

PMID- 8871863
TI  - Hexagonal keratotomy--should we still be trying?
AB  - BACKGROUND: I present my limited but positive experience with hexagonal
      keratotomy for hyperopia. METHODS: Eighteen consecutive eyes of 12 patients
      underwent hexagonal keratotomy during 1993. In addition to the primary
      procedures, 14 enhancements were required in seven eyes for both astigmatism and
      undercorrection. Surgical planning was based on refractive data only. All
      surgeries were performed by one surgeon using the open hexagonal keratotomy
      pattern. RESULTS: The patients' average age was 56 years (range, 38 to 67 years).
      Fourteen eyes were corrected for emmetropia. They had an average preoperative
      refraction of +2.22 +/- 0.64 diopters (D) and an average postoperative refraction
      of +0.11 +/- 0.49 D. Four eyes were corrected for near vision (-2.00 D). They had
      an average preoperative refraction of -0.53 +/- 0.83 D, and postoperatively their
      average refraction was -1.78 +/- 0.50 D. All four could read J1 without
      correction postoperatively. No eye lost more than one line of spectacle-corrected
      visual acuity; none had a major sight-threatening complication. CONCLUSIONS:
      Hexagonal keratotomy can correct 3.50 D or less of hyperopia. Conservative
      surgery with one major reoperation procedure is suggested. Because of the highly
      variable results noted in the literature and several reports of significant
      complications, I no longer perform or recommend hexagonal keratotomy.

PMID- 8871864
TI  - Histologic changes and wound healing response following 10-pulse noncontact
      holmium:YAG laser thermal keratoplasty.
AB  - BACKGROUND: Noncontact holmium:YAG laser thermal keratoplasty (Ho:YAG LTK) is a
      promising new technology for correction of hyperopia and astigmatism. We studied
      the acute histologic changes and wound healing response following Ho:YAG LTK
      performed with treatment parameters encompassing those used in clinical studies.
      METHODS: We performed 10-pulse noncontact Ho:YAG LTK on three human corneas 1 day
      before their removal at penetrating keratoplasty and on six New Zealand white
      rabbit corneas followed for up to 3 months. Tissues were studied with light and
      transmission electron microscopy and immunohistochemistry. RESULTS: The amount of
      acute tissue injury increased according to the pulse radiant energy. In human
      corneas, changes in the irradiated zones included epithelial cell injury and
      death, loss of fine filamentous structure in Bowman's layer, disruption of
      stromal lamellae, and keratocyte injury and death. In the rabbit corneas, similar
      acute changes were noted. By 3 weeks, epithelial hyperplasia and stromal
      contraction were present. Wound healing in the rabbits included repair of the
      epithelial attachment complex, keratocyte activation, synthesis of type I
      collagen, partial restoration of stromal keratan sulfate and type VI collagen,
      and retrocorneal membrane formation. CONCLUSIONS: Noncontact Ho:YAG LTK produces
      acute epithelial and stromal tissue changes and in rabbit corneas stimulates a
      brisk wound healing response.

PMID- 8871865
TI  - Rationale for abandoning the circumferential wedge resection procedure for high
      myopia.

PMID- 8871866
TI  - Evolving coverage in reporting refractive surgery in the popular press.

PMID- 8871867
TI  - Bacterial keratitis after photorefractive keratectomy.
AB  - Two patients who had excimer laser photorefractive keratectomy (PRK) for myopia
      developed bacterial keratitis, one from Staphylococcus epidermidis and the other
      with a negative culture. Both were treated with topical antimicrobial agents. One
      eye recovered an uncorrected visual acuity of 20/20. The other was left with a
      moderate subepithelial scar and an uncorrected visual acuity of 20/150.

PMID- 8871868
TI  - Slipped flap, irregular astigmatism, and undercorrection after automated lamellar
      keratoplasty.

PMID- 8871869
TI  - Hepatitis B virus transcriptional activators: mechanisms and possible role in
      oncogenesis.
AB  - The hepatitis B virus (HBV) genome encodes a 154 amino acid protein termed X
      (HBx, hepatitis B x protein), which is a promiscuous transcriptional activator of
      polymerase II and III promoters. HBx upregulates a wide range of cellular and
      viral genes and is thought to facilitate viral pregenome and mRNA transcription;
      however, its precise role in the viral replication cycle remains to be
      elucidated. The functional mechanisms of HBx appear very complex. It was shown to
      activate transcription factors AP-1 and NF-kappa B vis cytoplasmic pathways
      including ras-MAP kinase. In contrast, nuclear HBx is thought to activate the
      transcriptional machinery directly. A second transcriptional activator protein
      (Mst, middle s transactivator) is encoded by 3'-truncated preS2/S sequences of
      integrated HBV DNA, but not by the intact viral gene. HBx and Mst may contribute
      to the pathogenicity of chronic hepatitis B and are suggested to promote
      hepatocyte transformation via upregulation of cellular proto-oncogenes. Further,
      HBx may enhance HBV related carcinogenesis by inactivation of the tumour
      suppressor gene product p53.

PMID- 8871870
TI  - Long-term interferon-alpha treatment of children with chronic hepatitis delta: a
      multicentre study.
AB  - We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children
      with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26
      paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly
      for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance
      and tolerability were acceptable. At the end of therapy a complete biochemical
      response [normalization of alanine aminotransferase (ALT)] occurred in 12
      children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in
      10 cases (five in MTG and five in LTG). Two patients from the LTG had normal
      liver function tests during 12 months of follow-up. Six of the eight hepatitis B
      e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus
      (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later
      in two children. HDV RNA, present in 10/10 cases of MTG before treatment,
      persisted after 12 months IFN therapy in 3/10. One year after stopping therapy,
      8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta
      antigen (HDVAg) from the liver. No significant improvements in liver histology
      were seen in both groups. Our experience suggests that IFN-alpha treatment in
      children with chronic type D hepatitis has a transient effect, and long-term
      treatment does not appear to induce a greater therapeutic benefit in terms of
      biochemical and virological response.

PMID- 8871871
TI  - The use of deferoxamine infusions to enhance the response rate to interferon
      alpha treatment of chronic viral hepatitis B.
AB  - An individual's iron status may affect the response rate achieved with the use of
      interferon (IFN) as therapy for chronic viral hepatitis. A total of 27 patients
      with chronic hepatitis B viral infection, who had elevated serum ferritin levels,
      were randomized to receive either IFN 5 MU, three times weekly by subcutaneous
      injection alone (n = 14) or in combination with cycles of deferoxamine at a dose
      od 80 mg kg-1 per cycle (n = 13) administered over 3 consecutive days, to reduce
      their iron and maintain a serum ferritin level less than 250 ng ml-1. All
      deferoxamine-treated patients were on a low iron-containing diet. An IFN response
      was defined as a normalization of the serum alanine aminotransferase (ALT) level
      and seroconversion from hepatitis B e antigen (HBeAg) positivity to hepatitis B e
      antibody (HBeAb) positivity. The deferoxamine-treated group experienced a
      reduction in their serum ferritin level to 226 +/- 73 ng ml-1 as a result of the
      deferoxamine treatment. Six of the 13 (46%) deferoxamine-treated patients and two
      of the 14 (14%) control patients normalized their ALT levels. Seven of the 13
      (54%) deferoxamine but only 14% of the IFN-treated group seroconverted to HBeAb
      positivity. A greater rate of histological improvement and loss of hepatitis B
      virus (HBV) DNA was seen in the deferoxamine-treated group. Two of the
      deferoxamine-treated patients were treated only once, two were treated twice,
      seven were treated three times and two were treated four times to achieve a
      ferritin level below 250 ng ml-1. Based on these data, we conclude that
      deferoxamine infusion enhances the rate of response to IFN in subjects with
      chronic hepatitis B. The precise mechanism of this phenomenon is not clear.

PMID- 8871872
TI  - Relationship between the serum alanine aminotransferase level at the end of
      interferon treatment and histologic changes in wild-type and precore mutant
      hepatitis B virus infections.
AB  - Unravelling the role of interferon (IFN) in the treatment of chronic hepatitis B
      compliance by many factors. Several mutant forms of hepatitis B virus (HBV) have
      recently been discovered; the most common of these is the precore mutant,
      characterized by hepatitis B e antigen (HBeAg) negativity and hepatitis B e
      antibody (HBeAb) positivity in an individual with an active HBV infection. The
      aim of this study was to compare the response rate to IFN therapy in patients
      with wild-type HBV infection and in individuals infected with the precore mutant.
      A second aim was to evaluate the role of an increased serum ferritin in terms of
      the IFN response rate in these two different types of HBV infection. IFN therapy
      was administered at a dose of 5 MU subcutaneously three times weekly for 6 months
      to 41 individuals with a chronic wild-type hepatitis B infection and 16
      individuals with a precore mutant chronic HBV infection. An IFN response was
      defined as normalization of the serum alanine aminotransferase (ALT) level and an
      HBeAb to HBeAb seroconversion (in wild-type hepatitis infection), and a
      normalization of the serum ALT in individuals infected with a precore mutant
      infection. At entry, the two groups were matched for age, gender, serum ALT,
      serum iron, total iron binding capacity (TIBC), serum ferritin and liver
      histology. Forty-six per cent of the subjects with wild-type disease responded to
      IFN therapy. By contrast, only four of the 16 cases (25%) of the precore mutant
      cases responded (p < 0.05). Ferritin levels correlated well with the type of IFN
      response; as the serum ferritin level increased, the response rate to IFN
      declined. Hapatic infection caused by a precore HBV mutant is more resistant to
      IFN therapy than wild-type infection. The serum ferritin level appears to
      influence the type of IFN response achieved. Individuals with a serum ferritin
      level greater than 300 ng ml-1 failed to respond to IFN in 93% of the cases
      studied.

PMID- 8871874
TI  - The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on
      hepatitis B vaccination in haemodialysis patients.
AB  - Haemodialysis patients often fail to respond to hepatitis B vaccination. In this
      pilot study, 15 patients previously non-responsive to at least three 40
      micrograms doses of hepatitis B vaccine were given 0.5, 5 or 10 micrograms kg-1
      granulocyte-macrophage colony-stimulating factor (GM-CSF) subcutaneously 24 h
      prior to booster vaccination with a hepatitis B vaccine. Seven of the 15 patients
      developed antibody to hepatitis B surface antigen (HBsAb) (35-7240 IU L-1) upon
      initial vaccination with GM-CSF and two of four individuals responded with low
      HBsAb titres of 15 and 60 IU L-1 when revaccinated with hepatitis B surface
      antigen (HBsAg) and twice the dose of GM-CSF. The application of GM-CSF was
      associated with adverse effects that were, in general, mild to moderate in
      severity and appeared to be dose dependent. Two patients, both receiving 10
      micrograms kg-1 GM-CSF discontinued the study because of severe hypotension.

PMID- 8871873
TI  - Hepatitis C virus infection in patients with clinically diagnosed alcoholic liver
      diseases.
AB  - To determine the incidence of hepatitis C virus (HCV) infection in patients with
      alcoholic liver disease (ALD), serum samples from 252 patients with ALD were
      tested for anti-HCV and HCV RNA. Serial sera of these patients were collected and
      stored under optimal conditions to allow exact quantification of HCV RNA. Fifteen
      patients who visited our hospital during the same period of time with chronic HCV
      infections served as controls. In those with ALD, anti-HCV and HCV RNA were
      positive in 55.5% and 41.2%, respectively. Patients with histologically diagnosed
      chronic hepatitis and hepatocellular carcinoma had much higher prevalence rates
      of HCV RNA (84% and 100%, respectively) compared to those with fatty liver
      (4.3%), hepatic fibrosis (10.1%) and alcoholic hepatitis (22.2%) (P < 0.01).
      Although no difference in serum HCV RNA levels was observed between the patients
      with both ALD and chronic HCV infection and those with chronic HCV infection
      alone, HCV RNA levels significantly (10-fold) dropped after abstinence in nearly
      half of the patients (P < 0.01). These data indicate that HCV infection in
      patients with ALD promotes progression of liver disease, and abstinence from
      alcohol is associated with a reduction in serum HCV RNA levels.

PMID- 8871875
TI  - Rare pre-core stop-codon mutant nt. 1897 predominates over wide-spread mutant nt.
      1896 in an unusual course of chronic hepatitis B.
AB  - We present a patient with an unusual course of hepatitis B e antigen (HBeAg)
      negative chronic hepatitis B who had repeated reactivations of his disease
      progressing to cirrhosis with terminal liver failure. Each flare up presented
      like an acute hepatitis with very high titres of hepatitis B virus (HBV) and high
      inflammatory activity followed by rapid clearance of viraemia. The pre-core
      genome of HBV isolated from sera during 5 years of follow up was analysed. Direct
      sequencing of polymerase chain reaction (PCR) products derived from consecutive
      sera showed a rare pre-core stop-codon mutation at nucleotide (nt.) 1897 G --> A
      with an accompanying mutation nt. 1857 C --> T as well as a stop-codon mutation
      nt. 1896 G --> A. By cloning and sequencing of PCR products the mutant strain
      with mutation nt. 1897 was shown to predominate over viral strains with a
      mutation nt. 1896 during the course of disease, although the stop-codon mutation
      nt. 1896 in general is observed more frequently. Both mutations allow viral
      replication by stabilizing the encapsidation signal 'epsilon'. This allowed HBV
      replication at a very high level as observed during flare ups. The absence of
      HBeAg may be responsible for the massive cytotoxic T-cell response towards
      hepatocytes which might explain the rapid progression to liver cirrhosis although
      no, or very little, HBV replication was observed for long periods. However, there
      is no clear explanation as to why the nt. 1897 mutant strain overwhelmed the
      other virus strains.

PMID- 8871876
TI  - Replication of hepatitis delta virus.
AB  - Hepatitis delta virus (HDV) is a unique viroid-like human pathogen that is always
      associated with hepatitis B infection. Replication of HDV involves the
      transcription of genomic RNA, probably by the host RNA polymerase II, by a
      rolling circle mechanism followed by self-cleavage and self-ligation. Editing of
      antigenomic RNA, possibly involving the enzyme adenosine deaminase, generates two
      functionally distinct forms of delta antigen. The molecular basis for HDV
      pathogenicity remains uncertain.

PMID- 8871877
TI  - Stimulation of human lymphocyte proliferation and CD40 antigen expression by
      phosphorothioate oligonucleotides complementary to hepatitis B virus genome.
AB  - We have studied the proliferation and CD40 antigen expression of lymphocytes, and
      the cytotoxicity to monocytes, of antisense phosphorothioate
      oligodeoxynucleotides complementary to the SP II promoter of HBV mRNA (sequence
      I) and the X gene (sequence II) in patients with chronic hepatitis B. The oligo
      sequence I stimulated proliferation of both T and, to a lesser extent, B cells.
      The percentage of cells expressing CD40 in T and B cell co-cultures increased
      from 4.2% to 13.8% after oligo stimulation in patients, while it increased form
      4.7% to 48.6% in healthy controls. The sense sequence (sequence III) of the X
      gene also enhanced the expression of CD40 antigen in patients with hepatitis B.
      The proportion of CD40 cells (26%) in a resting B-cell preparation from hepatitis
      B patients decreased to zero after a 5-day culture with sequence I, but IgG
      levels in the culture supernatant increased. The cytotoxic properties of
      monocytes were not influenced by the oligos. These findings indicate that
      antisense oligos against hepatitis B virus (HBV) have mitogenic effects on the
      proliferation of human lymphocytes in a non-specific manner and may activate T
      cells to express CD40 antigen.

PMID- 8871878
TI  - Whole genome analysis of hepatitis B virus from four cases of fulminant
      hepatitis: genetic variability and its potential role in disease pathogenicity.
AB  - The precore stop-codon variant of hepatitis B virus (HBV) has been associated
      with fulminant hepatitis but is also found in patients with persistent infection
      and chronic hepatitis. We have examined the possibility that the severe outcome
      of infection in patients with fulminant disease may be a result of additional
      genomic variation. We sequenced the entire HBV genome from three patients of
      Greek and one patient of Chinese origin with fulminant hepatitis, and from two
      patients with hepatitis B e antigen (HBeAg) positive chronic infection from the
      same regions, using direct sequencing of amplified viral DNA. Three of the
      fulminant cases were infected with the precore stop-codon variant HBeAg negative)
      and the fourth with the wild-type (HBeAg) positive virus. We compared sequences
      from our four fulminant isolates, and an additional fulminant isolate reported by
      others, with HBeAg positive carriers from the same regions and 12 published HBV
      genomes. There was a higher number of nucleotide and amino-acid substitutions
      throughout the HBV genome in the precore variant fulminant sequences than in the
      wild type. A cluster of mutations previously identified in the X region (126-132)
      in sequences reported in Japanese patients and encompassing the Enhancer II-Core
      Promoter region (1751-1768), were not found in our patients. We conclude that
      although there are no changes common to all sequences of HBV isolates from
      fulminant cases, some of these changes are in recognized cis-acting regulatory
      elements, whilst others are in the immediate vicinity of such elements. The
      effect of these mutations on viral genome transcription must now be determined.

PMID- 8871879
TI  - Lack of association between type of hepatitis C virus, serum load and severity of
      liver disease.
AB  - Chronic infection with the hepatitis C virus (HCV) may lead to a variety of
      hepatic lesions from benign inflammation to liver cancer, but the relationships
      between infection and development of liver disease are poorly understood. To
      assess whether virus type and load are of pathogenetic importance, 197 Italian
      carriers with various hepatic lesions were investigated consecutively. Of these,
      187 (95%) patients had serum HCV RNA, by reverse transcription-polymerase chain
      reaction (RT-PCR) with a median level of 1003 x 10(3) genomic equivalents ml-1
      according to the branched-DNA assay (b-DNA). One hundred and seven patients (54%)
      had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed
      serotypes and 42 (21%) had no specified serotype. One hundred and thirty four
      patients were also tested for genotype. The genotype distribution was as follows:
      17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had
      genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4
      and 1 (1%) had mixed genotype 1a + 3a. No virus type was associated with any
      particular histological diagnosis and all were equally distributed between
      progressive and non-progressive liver disease groups. Serum HCV-RNA levels were
      similar in the liver diseased groups. By analogy to hepatitis B, there was no
      direct correlation between type and level of viraemia and the severity of the
      underlying liver damage.

PMID- 8871880
TI  - Combination low-dose lymphoblastoid interferon and thymosin alpha 1 therapy in
      the treatment of chronic hepatitis B.
AB  - This open label study was initiated to assess the safety and efficacy of
      lymphoblastoid interferon-alpha (IFN-alpha) and thymosin alpha 1 (T alpha 1) in
      the treatment of 11 patients with chronic hepatitis B, who had failed to respond
      to standard IFN-alpha 2b therapy, and in four interferon naive patients. These
      fifteen hepatitis B surface antigen (HBsAg) positive and serum hepatitis B virus
      (HBV) DNA positive patients were given T alpha 1 (1 mg) subcutaneously (s.c.) on
      4 consecutive days. Low-dose lymphoblastoid IFN-alpha (3 MU) was administered
      intramuscularly (i.m.) on the fourth day. Beginning with the second and for the
      subsequent 25 weeks, patients self-administered T alpha 1 twice weekly in the
      morning followed, 12 h later, by 3 million units (MU) lymphoblastoid IFN-alpha.
      Patients were followed-up for 12 months. Nine (60%) of the 15 patients, including
      six (55%) of the 11 patients previously treated with IFN-alpha 2b, responded by
      losing serum HBV DNA and normalizing alanine aminotransferase (ALT) values. Six
      of the nine responders seroconverted to HBsAg negativity. Significant
      improvements in the Knodell histological activity index were observed in the
      responders and no significant adverse effects were observed. Combination low-dose
      lymphoblastoid IFN-alpha and T alpha 1 treatment may provide a safe and
      potentially effective therapeutic approach in chronic hepatitis B. These results
      require confirmation in future randomized controlled studies.

PMID- 8871881
TI  - Hepatitis E virus infection in north-east Italy: serological study in the open
      population and groups at risk.
AB  - Developed western countries are considered to be relatively free from endemic
      foci of hepatitis E virus (HEV) infections. The aim of this study was to assess
      the seroepidemiology of HEV in north-east Italy. Of the 2361 individuals studied
      1889 were representative of the general population and 472 were from groups at
      high risk for viral infections: 279 drug users and 193 patients on chronic
      haemodialysis. All sera were tested for hepatitis C virus antibody (HCVAb), human
      immunodeficiency virus antibody (HIVAb) and for hepatitis B virus (HBV) serology.
      Two solid-phase enzyme-linked immunosorbent assays (ELISA) were used to study the
      seroepidemiology of HEV IgG, the first (using recombinant antigens) for
      confirmation of initially reactive samples. The prevalence of circulating
      hepatitis E virus antibody (HEVAb) was 2.6% in the open population, 5.4% among
      drug users and 9.3% among patients on chronic haemodialysis. In the open
      population a positive relationship between age and prevalence of HEVAb was
      observed. A relationship between presence of HEVAb and serological evidence of
      previous HBV or HCV infections was also observed in this study. It was concluded
      that HEV infections are present in north-east Italy and are more frequent among
      subjects at risk for blood-borne viral infections. The positive correlation,
      observed in the open population, between age and prevalence of HEVAb suggests the
      presence of a cohort effect.

PMID- 8871882
TI  - Hepatitis E virus infection in patients from Saudi Arabia with sickle cell
      anaemia and beta-thalassemia major: possible transmission by blood transfusion.
AB  - The seroprevalence of antibodies against hepatitis E virus (HEV) and hepatitis C
      virus (HCV) was investigated in Saudi children with sickle cell anaemia (SCA) (50
      patients: 28 boys, 22 girls; age range 2-14 years) and beta-thalassemia major (28
      patients: 12 boys, 16 girls; age range 2-12 years). The SCA patients were from
      the Gizan area (South) while the thalassemics were from the Riyadh area (Central
      province). The prevalence of hepatitis E virus antibody (HEVAb) in patients with
      SCA (18.0%) and in those with beta-thalassemia major (10.7%) was higher than in
      the control groups (5.5% and 2.8%) but this did not reach the level of
      statistical significance. In contrast to the situation with HEV, hepatitis C
      virus antibody (HCVAb) positivity was significantly higher in patients with SCA
      (16.0%) and in thalassemics (57.1%) than in the respective control groups.
      Although the difference in HEV seropositivity between beta-thalassemia major, SCA
      patients and their respective controls is not statistically significant, the
      possibility of blood-borne HEV in the Saudi population cannot be excluded.
      Further investigations using HEV-specific polymerase chain reaction techniques
      are required to confirm whether transmission of HEV through blood preparations or
      transfusion is possible.

PMID- 8871883
TI  - Stability of hepatitis C virus RNA in serum from samples collected in a closed
      tube system for serum separation and transport, as measured by a quantitative
      competitive PCR assay.
AB  - Recovery of hepatitis C virus (HCV) RNA, after variable time intervals from
      collection, was assessed using a closed-tube system for collection, separation
      and transport (SST tubes). Blood from four hepatitis C-infected patients was
      collected in 12 SST tubes and centrifuged within 1 to 3 h of collection. Tubes
      were then left 0, 8, 12, 24, 48 and 72 h at room temperature and at 4 degrees C
      before removing serum. Hepatitis C virus RNA levels were measured by quantitative
      polymerase chain reaction (PCR) using the AMPLICOR HVC MONITOR assay. Hepatitis C
      virus RNA levels in these samples were stable for at least three days at both
      temperatures. Polymerase chain reaction signals never decreased by more than 0.5
      log. The reproducibility of the assays showed that the quantitative PCR method
      can be used with the storage conditions tested here. Our data suggests that
      processing blood in SST tubes may be very useful in following hepatitis C virus
      RNA titres in infected patients, especially those receiving treatment.

PMID- 8871884
TI  - A double blind, placebo-controlled study to assess the effect of famciclovir on
      virus replication in patients with chronic hepatitis B virus infection.
AB  - This is the first double-blind controlled study of famciclovir, an oral antiviral
      agent, as potential therapy for chronic hepatitis B virus (HBV) carries. A fall
      of more than 90% in HBV DNA levels was noted in six of 11 evaluable patients
      treated with a 10 day course of oral famciclovir. Further studies with more
      prolonged therapy are ongoing.

PMID- 8871885
TI  - G proteins, hypertension, and coronary heart disease--novel findings and
      hypotheses.

PMID- 8871886
TI  - Arginine vasopressin and oxytocin increase intracellular calcium and cAMP in
      human glomerular epithelial cells in culture.
AB  - The signal transduction linkages of arginine vasopressin (AVP) and oxytocin
      receptors were investigated in human glomerular epithelial cells (GEC) in
      culture. AVP (ED50, 10(-7) mol/l) and oxytocin (ED50, 3 x 10(-8) mol/l) induced a
      rapid, transient and dose-dependent increase in [Ca2+]i as detected by fura-2
      microfluorimetry. The baseline of [Ca2+]i in human GEC was 109 +/- 2.8 nmol/l (n
      = 60). The V1a receptor antagonist [d(CH2)5(1), Tyr(Me)2, Arg8]-vasopressin
      inhibited the AVP-(IC50, 5 x 10(-9) mol/l) and oxytocin-induced (IC50, 3 x 10(-8)
      mol/l) increase in [Ca2+]i in a dose-dependent manner. Both, AVP and oxytocin
      caused accumulation of cAMP. The AVP-stimulated cAMP increase was blocked by
      pretreatment of human GEC with the V1a receptor antagonist (10(-7) mol/l),
      whereas the oxytocin-induced cAMP accumulation remained uninfluenced. In
      conclusion the present results indicate that: (1) V1a receptor activation, AVP
      and oxytocin induce a transient elevation in [Ca2+]i in human GEC; (2) AVP and
      oxytocin cause cAMP accumulation; (3) the AVP-induced cAMP accumulation is
      inhibited by a V1a receptor antagonist, whereas (4) the oxytocin response showed
      no effect. In addition, a different receptor might be possible, at least in
      oxytocin-induced-cAMP accumulation.

PMID- 8871887
TI  - Regulation of rat proximal tubule Na/H exchange by protein kinase C.
AB  - The effect of protein kinase C (PKC) activation on fluid and bicarbonate
      transport in renal tubules has been discussed controversially. Stimulation and
      inhibition have been shown to depend on factors such as experimental model and
      exposure time to the mediator of enzyme activation. We studied the role of PKC
      activation by phorbol-12-myristate-13-acetate (PMA) and by 1,2-dioctanoyl
      glycerol (DOG) in proximal bicarbonate reabsorption (JHCO3-) by 'in vivo'
      stationary microperfusion and ion-exchange resin microelectrode determination of
      luminal pH. Both PMA (10(-8) mol/l) and DOG (10(-3) mol/l) added to lumen or to
      peritubular capillaries reduced the net JHCO3- significantly. When added to
      lumen, the inhibition was 44 and 32%, respectively. This reduction did not
      involve changes in lumen stationary pH, but was mediated by a marked increase in
      the halftime of luminal bicarbonate disappearance; from 4.22 +/- 0.23 to 6.27 +/-
      0.51 s with PMA and from 3.90 +/- 0.25 to 6.33 +/- 0.48 s with DOG. This effect
      was intensified by 10(-6) mol/l okadaic acid, a phosphatase inhibitor (inhibition
      of JHCO3- increased to 61%), and reduced by 30% by 10(-6) mol/l H7, an inhibitor
      of PKC. H89, a protein kinase A inhibitor, did not affect the inhibitory action
      of PMA. Our data suggest that PKC activation reduces the rate of H ion secretion
      (bicarbonate reabsorption) in convoluted segments of rat renal proximal tubules
      and that phosphorylation of the Na+/H+ exchanger by this kinase is the cause of
      the reduction in net secretion of H ions.

PMID- 8871888
TI  - Monitoring of extracellular and total body water during haemodialysis using
      multifrequency bio-electrical impedance analysis.
AB  - Multifrequency bio-electrical impedance analysis (MFBIA) was evaluated as a
      technique for monitoring changes in extracellular and total body water (ECW and
      TBW, respectively) of 15 subjects during dialysis. Dilution analysis, using
      deuterium oxide and sodium bromide, was also performed on each subject before
      dialysis so that prediction equations for ECW and TBW based on the MFBIA measures
      could be developed. These prediction equations were then used to estimate water
      compartment volume changes during dialysis and compared with volumetric measures
      of the dialysate removed. The results show that MFBIA does not accurately measure
      ECW and TBW changes during dialysis. The MFBIA measures tend to overestimate the
      changes and are not sufficiently precise to be clinically useful.

PMID- 8871889
TI  - S-adenosylhomocysteine-hydrolase from bovine kidney: enzymatic and binding
      properties.
AB  - In the present study S-adenosylhomocysteine (SAH) hydrolase from the bovine
      kidney has been purified to apparent homogeneity by standard chromatographic
      procedures. The purified enzyme was free from adenosine deaminase activity and
      showed a one-banded pattern in SDS-PAGE with a monomer molecular mass of 47,500.
      The molecular mass of the native enzyme estimated by gel filtration was about
      190,000. The pI was 5.5. For hydrolysis of SAH we found a Km of 5.0 +/- 1.2
      microM and a V of 0.25 mumol/min/mg. In the direction of synthesis the Km for
      adenosine was 5.6 microM and V 0.53 mumol/min/mg. The enzyme activity was
      inhibited in the presence of adenosine with a Ki = 3 microM. In a second set of
      experiments we determined the binding characteristics of [3H]-adenosine to
      purified enzyme. The enzyme bound [3H]-adenosine with three apparent affinities:
      Kd1 = 6.8 +/- 0.7 nM and Bmax1 = 0.24 +/- 0.04 nmol/mg protein; Kd2 = 387 +/- 41
      nM and Bmax2 = 1.4 nmol/mg protein, and Kd3 = 7.05 +/- 0.9 microM and Bmax3 = 9
      nmol/mg protein. Binding of 25 nM [3H]-adenosine obeyed a monophasic reaction
      with a k+1 value of 0.025 min/nM. Dissociation of [3H]-adenosine-SAH hydrolase
      complex was markedly temperature dependent. After a 240-min incubation at 0
      degrees C only 5-10% and at 20 degrees C 75% were displaceable. A fraction of 25%
      bound [3H]-adenosine was not displaceable by unlabeled adenosine. Our data show
      that the renal SAH hydrolase exhibits similar enzyme kinetics as the well
      characterized SAH hydrolase from liver. The amount of SAH hydrolase present in
      renal tissues (1.4 nmol/g wet weight) could account almost entirely for the
      binding of renal tissue adenosine. Finally, we report for the first time a high
      affinity binding site of SAH hydrolase for adenosine, which remains unexplained
      at present.

PMID- 8871890
TI  - The adrenal glands as suppliers of plasma L-Dopa and sources of urinary dopamine.
AB  - Dopamine (DA) is a natriuretic hormone synthesized in the kidneys by conversion
      of filtered 3,4-dihydroxyphenylalanine (L-Dopa), and is activated during
      hypervolaemia and increased dietary sodium intake. The natriuretic activity of
      endogenous DA is controversial, however, and the regulation of renal DA synthesis
      has yet to be explained. It has been suggest that the adrenals may be major
      suppliers of plasma L-Dopa on the basis of their catecholamine biosynthesis. A
      study was conducted in rats to elucidate the role of the adrenal glands as
      dynamic suppliers of L-Dopa to plasma, and thereby as sources of urinary DA.
      Adrenal venous and systemic arterial plasma concentrations and urinary excretion
      of L-Dopa, DA and sodium were measured before and during acute isotonic volume
      expansion (VE; 5% of body weight). One group of animals were acutely
      adrenalectomized (ADX group) to elucidate the ultimate importance of the adrenals
      in VE-induced renal sodium and DA excretion. In intact animals, the L-Dopa
      concentration was 62% higher in adrenal venous than in systemic arterial plasma
      under control conditions, and 42% higher during VE. The adrenaline concentration
      was 65 times higher in adrenal venous than in systemic arterial plasma before VE
      and 56 times higher during VE. The L-Dopa concentration in systemic arterial
      plasma and the urinary L-Dopa excretion were similar in intact and ADX animals.
      In intact animals, renal sodium and DA excretion during VE increased more than 13
      fold and by 42%, respectively. The corresponding values in ADX animals did not
      differ from those in the intact animals (more than 14-fold and 36%,
      respectively). It is concluded that the adrenal glands are only minor suppliers
      of plasma L-Dopa and minor sources of urinary DA. The regulation of plasma L-Dopa
      remains to be explained.

PMID- 8871891
TI  - Reversal of the antinatriuretic effect of prostaglandin E2 by verapamil in the
      rat.
AB  - Previous studies have demonstrated that prostaglandin E2 (PGE2) infusion
      increases intrarenal angiotensin-II (ANG-II) formation and decreases sodium
      excretion in the rat. PGE2 infusion may have direct tubular effects or indirect
      effects through increased intrarenal ANG-II. In the present study, the calcium
      channel blocker verapamil was used to determine whether it would reverse the PGE2
      induced decrease in sodium excretion. To minimize any systemic and hemodynamic
      influences, verapamil and PGE2 were infused directly into the renal interstitium
      via a chronically implanted matrix. Fractional sodium excretion (FENa),
      glomerular filtration rate (GFR), mean arterial pressure (MAP), and plasma renin
      activity (PRA) were measured before and during renal interstitial infusion of
      PGE2 (10(-5) M) and/or verapamil (10(-3) M) in rats pretreated with indomethacin.
      The renal interstitial infusion of PGE2 alone significantly decreased FENa (delta
      1.0 +/- 0.2%), whereas the addition of verapamil reversed the effect of PGE2 and
      significantly increased FENa (delta 2.6 +/- 0.3%, n = 9). The renal interstitial
      infusion of verapamil alone markedly increased FENa (delta 1.7 +/- 0.3%, n = 7),
      and this natriuresis was accompanied by a significant decrease in PRA (delta-0.6
      +/- 0.1 ng/ml/h, p < 0.05). The addition of PGE2 to the interstitial infusion did
      not further affect FENa or PRA. There was a significant difference between the
      effect of interstitial PGE2 infusion and interstitial PGE2 infusion and
      interstitial verapamil infusion on PRa (delta 1.9 +/- 0.8 vs. delta -0.6 +/- 0.1
      ng/ml/h, p < 0.05). GFR and MAP remained unchanged in response to the renal
      interstitial infusion of PGE2 and/or verapamil. In conclusion, verapamil reversed
      the PGE2-induced antinatriuresis in the rat.

PMID- 8871892
TI  - The glomerular filtration rate during pregnancy: saline infusion enhances the
      glomerular filtration rate in the pregnant rat.
AB  - The glomerular filtration rate (GFR) of pregnant rats is generally believed to
      exceed non-pregnant values. This notion is primarily based upon standard insulin
      clearances. However, the insulin clearance requires continuous infusion of
      insulin usually dissolved in saline. Since saline infusion per se in pregnancy
      may influence the GFR, in the present study the effect of saline infusion upon
      the GFR in pregnant as compared with cyclic rats was investigated using various
      methods. The standard insulin clearance was compared using the standard 51Cr-EDTA
      method which does not require saline infusion. Clearance of insulin dissolved in
      glucose (5% in distilled water) instead of saline was also tested, while the 51Cr
      EDTA method was employed using additional fluid infusion with either saline or 5%
      glucose in distilled water in an identical manner as compared with the insulin
      method. The GFR was also studied in conscious rats using 51Cr-EDTA clearance with
      and without fluid infusion. The distribution volume of 51Cr-EDTA was measured in
      nephrectomized rats (pregnant and cyclic) with and without saline or glucose
      infusions. The results show a significant increase of the GFR in pregnant rats as
      compared with cyclic rats only when saline was infused during the measurement;
      thus, GFR measurements without fluid infusion or replacement of saline by glucose
      during the measurements did not show a significant increase of GFR in pregnant
      rats. The volume of distribution per gram body weight of 51Cr-EDTA after saline
      infusion, but not after glucose infusion, was significantly increased as compared
      with the values obtained without additional infusion. It is concluded that the
      increase of the GFR seen in pregnant rats when either the 51Cr-EDTA method or the
      insulin method is accompanied by saline loading is rather due to infusion of
      saline in the pregnant animal and not a result of the pregnant condition per se.

PMID- 8871893
TI  - Renal phospholipid metabolism in streptozotocin-induced diabetic rats.
AB  - The effect of acute and chronic streptozotocin-induced diabetes on phospholipid
      metabolism in papillary, medullary and cortical slices was studied. No changes
      were observed in either the phospholipid content or composition in the papilla,
      medulla and cortex from acute and chronic diabetic rats. With reference to (U
      14C)glycerol incorporation in the papilla from chronic diabetic rats, it
      increased in PtdCho, PtdIns and PtdEtn. In the medulla, the incorporation to
      PtdCho decreased in the acute diabetic state, while in the chronic diabetic state
      the incorporation to PtdCho and PtdIns decreased. No changes were observed in
      cortical phospholipids from diabetic rats. As regards 23P-sodium orthophosphate
      incorporation to phospholipids, while it increased in PtdCho, PtdIns and PtdEtn
      in the papilla from acute and chronic diabetic rats, in the medulla from both
      groups, the incorporation in PtdCho and PtdIns decreased, and in the cortex from
      acute diabetic rats it decreased only in PtdIns. Even though no changes were
      detected in phospholipid composition, alterations in phospholipid metabolism were
      induced by experimental diabetes.

PMID- 8871894
TI  - The symbolic atlas of the brain: handling non-visual information associated with
      neuroanatomy.
AB  - The Symbolic Atlas of the brain is a novel software tool which enables the user
      to store and access non-visual information associated with the brain anatomy. The
      atlas is potentially capable of storing any information about neuroanatomical
      objects. The user can construct a number of atlases, each containing a different
      kind of information related to functionality, pathology, symptoms and other
      facts. The Prolog database that underpins the storage of knowledge frames
      provides scope for nearly unconstrained usage and manipulation of the stored
      data, including reasoning with and about data and complex querying. The access to
      the stored information is provided in an intuitive way, through a simple 'click'
      on an anatomical structure either in a two- or three-dimensional atlas, or on an
      outline of a structure superimposed on a real image slice. A pilot educational
      and clinical use of the atlas indicates its great potential, especially in the
      are of education.

PMID- 8871895
TI  - Decision support for insulin regime prescription based on a neural-network
      approach.
AB  - Insulin regime prescription is performed by medical personnel based on a number
      of patient related factors such as age, activity, type of current medication,
      desirable control, whether the patient belongs to a special category, for example
      whether he has fever or has undergone surgery, etc. No general rules apply so
      that each expert adopts his/her own rules for insulin regime specification based
      on his/her experience, intuition and expertise. This is why there is very little
      in medical literature concerning this issue. This paper describes a system
      supporting the decision making of medical personnel with respect to the
      specification of insulin regimes, based on a neural network methodology. In
      particular, an adaptive version of the backpropagation algorithm is used for the
      system training. This algorithm dramatically reduces training time and guarantees
      the monotonically decreasing nature of the error function. The training set
      consisted of one hundred and eight training vectors. The system offers support
      with respect to diabetes management by insulin regime prescription. The choice of
      the factors participating in the decision making of the system described in this
      paper, is based on an extensive interviewing of a number of diabetologists in
      leading diabetological centres in Greece.

PMID- 8871896
TI  - A microcomputer teaching and decision-support system for emergency medicine: use
      of hypermedia and artificial intelligence in combination.
AB  - Hospital emergency units are submitted to a continuous intensive and polyvalent
      practice of medicine. In addition to the few experienced physicians, the medical
      staff is often made up of young and unskilled students and residents. The ability
      to reach at any time a wide and flexible knowledge is of the utmost importance to
      improve the quality of care given to patients and to perfect bedside teaching.
      The purpose of this work was to present a computerized system, a kind of shell,
      using, in combination, artificial intelligence and hypertext/hypermedia tools. A
      modular architecture is presented integrating two entities: an illustrated
      encyclopedic hypertext network and several expert modules based on production
      rules concerning well-limited fields of medicine (basic clinical problem-solving,
      metabolic and acid-base disorders). An interface using the World Wide Web (WWW)
      will soon be proposed.

PMID- 8871897
TI  - Using CommonKADS to create a conceptual model of a guideline system for breast
      cancer prognosis.
AB  - One of the major aspects in breast cancer research is the identification of
      prognostic factors accurate enough to define different therapeutic decisions;
      each prognostic factor on its own is insufficient for the prediction of the
      biological behaviour of the tumour, but a combination of these parameters is
      necessary. The work described here focuses on the definition of a conceptual
      knowledge model of the prognosis of breast cancer. Our approach to the
      conceptualization of the problem follows the CommonKADS (Knowledge Acquisition
      and Design Structuring) Library for Expertise Modelling. The aim of this work is
      to provide a first conceptualization of breast cancer prognosis while evaluating
      the efficacy of the CommonKADS methodology in facing the problem.

PMID- 8871898
TI  - Theoretical considerations on medical concept representation.
AB  - Concepts are seen as building elements of more compositional information objects
      in medicine. Consequently, representation of medical concepts plays a critical
      role in any information system. The authors present some of the key problems
      which need solution, such as definition of medical domain, analysis of internal
      structure, different subsets of medical concepts, and the problem of the
      'elementary' concepts. As a result of these considerations we can conclude that
      the domain of medical concepts can hardly be delimited and consists of different
      subsets. These subsets need different representation methods according to their
      different nature. Some of these subsets have a hierarchic structure. In those one
      can find sometimes multiple hierarchies. We suggest avoiding multiple hierarchies
      in concept systems by the introduction of new dimensions.

PMID- 8871899
TI  - Health and welfare data on optical memory cards in Isehara city.
AB  - An off-line network system of health and welfare for elderly people using optical
      memory cards has been established in Isehara city (Japan) since 1991. 2775
      citizens have the cards and 24 offices have the terminals. It covers almost one
      third of people aged over 65 in Isehara city and almost all of the offices
      concerned with their health and welfare. About a half of holders use optical
      memory cards every time they visit these offices. The optical memory card holds
      data including basic data for health and welfare, health check data over 5 years,
      medical images with scripts and history of welfare services. All the data are
      used for medical care, health consultation and management of health and welfare
      services. A card can hold health and welfare data for a lifetime, and it is easy
      to expand the system. It has been a good experience for us, because the optical
      memory card system needs co-operation among citizens, medical association and
      local government, and the experience will help us to expand the system in the
      future.

PMID- 8871900
TI  - Role of pulse wave velocity for assessing autonomic nervous system activities in
      reference to heart rate variability.
AB  - Pulse wave velocity (PWV) is related to arterial wall elasticity, which in part
      is regulated by sympathetic nervous system activity. The present study
      investigated the potential for the simultaneous use of PWV and heart rate
      variability using noninvasive recordings in order to provide a quantitative
      evaluation of the sympathovagal interaction modulating cardiovascular functions.
      We obtained 10 indices from the PWV and heart rate (HR) time series of 92 healthy
      subjects (control group) and compared the results with those of 135 patients with
      diabetes mellitus or vertigo. Five indices were obtained from a PWV series, that
      is, the mean, the coefficient of variation (CV) during supine rest, those
      immediately after standing up unaided, and the change of the mean PWVs before and
      after standing. The rest of the indices were also obtained from the instantaneous
      HR series. Statistical analyses revealed significant differences in the change of
      the mean PWVs after standing, the mean and CV of resting HR, the mean and CV of
      standing HR, and the change of mean HRs in patients with diabetic neuropathy as
      compared with healthy subjects (p < 0.01). The change of the mean PWV immediately
      after standing allows for the assessment of peripheral vascular sympathetic
      functions, provided one uses HR variability indices simultaneously.

PMID- 8871901
TI  - Risk factors predicting exertional heat illness in male Marine Corps recruits.
AB  - A matched population-based case-control study was conducted on exertional heat
      illness (EHI) in male Marine Corps recruits in basic training at Parris Island,
      SC. Physical fitness and anthropometric measurements were obtained for 391 of 528
      cases of EHI identified in this population during 1988-1992, and 1467 of 1725
      controls matched to cases by initial training platoon. The risk for developing
      EHI increased with increase in body mass index (BMI = weight.height-2) as
      measured on arrival and with increase in time to complete a 1.5-mile run
      conducted during the first week. Recruits at highest risk for developing
      exertional heat illness had a BMI of 22 or more kg.m-2 and a 1.5-mile run-time
      for 12 of more minutes. These recruits had an eightfold higher risk for
      developing exertional heat illness during basic training when compared with those
      with BMI less than 22 kg.m-2 and 1.5-mile run-time under 10 min (P < 10(-6). Only
      one-fifth (18%) of male recruits met these criteria for high risk, but they
      accounted for nearly half (47%) of the exertional heat illness cases occurring
      during the 12-wk basic training course.

PMID- 8871902
TI  - Lower limb morphology and risk of overuse injury among male infantry trainees.
AB  - The effect of anatomic variation on the risk of overuse injuries has not been
      adequately evaluated. To determine the association of several common anatomic
      characteristics (genu varum, genu valgum, genu recurvatum, and lower limb length
      differences) with risk of overuse injury, we made prospective morphologic
      measurements of young men prior to beginning 12 week of Army infantry training.
      The training included frequent running, marching, calisthenics, and other
      vigorous activities. Lower extremity anatomic landmarks were high-lighted, and
      front- and side-view photographic slides were taken of the 294 study volunteers.
      The slides were compute digitized, and the following measures calculated: pelvic
      width to knee width ratio (to assess genu valgum/varum), quadriceps angle (Q
      angle), knee angle at full extension, and lower limb length differences. The
      cumulative incidence of lower limb overuse injury was 30%. Relative risk of (RR)
      of overuse injury was significantly higher among participants with the most
      valgus knees (RR = 1.9). Those with Q-angle of more than 15 degrees had
      significantly increased risk specifically for stress fractures (RR = 5.4).
      Anatomic characteristics were associated with several other types of injuries,
      including pain and nonacute muscle strain due to overuse. This pilot study
      provides evidence that some lower limb morphologic characteristics may place
      individuals at increased risk of overuse injuries.

PMID- 8871903
TI  - Changes in indicators of inflammation after eccentric exercise of the elbow
      flexors.
AB  - This study examined muscle swelling and changes in inflammatory markers in the
      blood following eccentric exercise-induced muscle damage. Subjects (N = 14) who
      had not been involved in a resistance training program performed 24 maximal
      eccentric actions of the elbow flexors. Muscle swelling was assessed by measures
      of the upper arm circumference (CIR), ultrasonography (USG), and magnetic
      resonance imaging (MRI). Plasma concentrations of interleukin-1 alpha,
      interleukin-1 beta, interleukin-2, interleukin-6, tumor necrosis factor-alpha,
      and plasma levels of C-reactive protein, cortisol, and zinc were analyzed.
      Established indicators of muscle damage (maximal isometric force, range of
      motion, muscle soreness, and plasma creatine kinase, aspartate aminotransferase,
      and lactate dehydrogenase activities) were also measured. All measures, including
      CIR and USG, except for MRI, were assessed immediately before and after and for 5
      d post-exercise. MRI was taken at pre- and 1, 3, 6, 10, 23, 31, and 58 d post
      exercise. All muscle damage indicators changed significantly after exercise. A
      large increase in CIR (> 20 mm) was found 4-5 d after exercise, and this
      coincided with USG, showing an increase in muscle thickness. The echointensity of
      USG increased with the enlargement of the elbow flexors. MRI displayed
      enlargement of the biceps brachii and brachialis cross-sectional area that
      started at 1 d, and lasted until 23 d, post-exercise. The most profound increase
      in the enlargement and signal intensity of the MRI was found 3 or 6 d after
      exercise. However, none of the plasma levels of inflammatory makers showed
      significant muscle swelling, which is indicative of muscle edema, but the
      inflammatory responses after exercise appear to be different from those
      accompanying infection or tissue injury.

PMID- 8871904
TI  - Lipoprotein(a) in endurance athletes, power athletes, and sedentary controls.
AB  - Elevated concentrations of lipoprotein(a) [Lp(a)] have been shown to be an
      independent risk factor for atherosclerotic disease. Physical activity and
      physical fitness have been shown to improve lipoprotein metabolism and reduce the
      risk of coronary artery disease. Studies on the influence of physical activity
      and physical fitness on Lp(a) levels including a large number of endurance as
      well as power athletes have not been performed before. Therefore, we determined
      parameters of physical fitness (maximal oxygen consumption), physical activity,
      and lipoproteins in 105 endurance athletes, 57 power athletes, and 87 sedentary
      young men. As expected, we found that endurance athletes with a good physical
      fitness had significantly higher concentrations of high-density lipoprotein
      cholesterol than power athletes and sedentary controls. Regarding mean Lp(a)
      levels (rocket immunoelectrophoresis), however, there were no significant
      differences between endurance athletes, power athletes, and sedentary controls.
      Even when including only those with Lp(a) values > 10 mg.dl-1, no differences
      were observed between the groups. These findings indicate that intensive training
      over years and good aerobic fitness improve the ratio of low-density lipoprotein
      to high-density lipoprotein cholesterol but have no or only minor effects on
      Lp(a) concentrations.

PMID- 8871905
TI  - Body mass index and daily physical activity in anorexia nervosa.
AB  - The level of daily physical activity in 11 non-hospitalized women with anorexia
      (age: 21-48 yr, body mass index (BMI): 12.5-18.3 kg.m-2), compared with 13 normal
      weight women (age: 20-35 yr, BMI 19.2-26.7 kg.m-2), was studied in relation to
      BMI. Daily physical activity over a 7-d period was determined from movement
      registration and by combining measurements of average daily metabolic rate
      (measured in a respiration chamber). Group averages of daily physical activity
      were similar for subjects with anorexia and control subjects. However, women with
      anorexia had either a low or a high level of daily physical activity, whereas
      most control subjects had a moderate level of daily physical activity. In the
      women with anorexia, daily physical activity was significantly related to BMI (r
      = 0.84). Subjects with a BMI > or = kg.m-2 were equally or more active compared
      with control subjects, while subjects with a BMI < 17 kg.m-2 were equally or less
      active compared with control subjects. The increased physical activity at BMI >
      or = 17 kg.m-2 is considered to be facilitated by an improving physical capacity
      combined with the advantages of a low body mass during weight-bearing activities.
      At lower BMI, undereating and declining physical capacity may have caused the
      observed decrease in daily physical activity.

PMID- 8871906
TI  - Physiological adaptations and countermeasures associated with long-duration
      spaceflights.
AB  - Since 1961, there have been more than 165 flights involving several hundred
      individuals who have remained in a space environment from 15 min to more than a
      year. In addition, plans exist for humans to explore, colonize, and remain in
      microgravity for 1000 d or more. This symposium will address the current state of
      knowledge in select aspects associated with the cardiovascular, fluid and
      electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The
      authors will focus on responses, mechanisms, and the appropriate countermeasures
      to minimize or prevent the physiological and biochemical consequences of a
      microgravity environment. Since exercise is frequently cited as a generic
      countermeasure, this topic will be covered in greater detail. Models for
      simulated microgravity conditions will be discussed in subsequent manuscripts, as
      will future directions for ground-based research.

PMID- 8871907
TI  - Cardiovascular adaptation to spaceflight.
AB  - This article reviews recent flight and ground-based studies of cardiovascular
      adaptation to spaceflight. Prominent features of microgravity exposure include
      loss of gravitational pressures, relatively low venous pressures, headward fluid
      shifts, plasma volume loss, and postflight orthostatic intolerance and reduced
      exercise capacity. Many of these short-term responses to microgravity extend
      themselves during long-duration microgravity exposure and may be explained by
      altered pressures (blood and tissue) and fluid balance in local tissues nourished
      by the cardiovascular system. In this regard, it is particularly noteworthy that
      tissues of the lower body (e.g., foot) are well adapted to local hypertension on
      Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to
      increase in local blood pressure. For these and other reasons, countermeasures
      for long-duration flight should include reestablishment of higher, Earth-like
      blood pressures in the lower body.

PMID- 8871908
TI  - Effect of spaceflight on the functional, biochemical, and metabolic properties of
      skeletal muscle.
AB  - This paper summarizes the effects of spaceflight on the functional,
      morphological, and biochemical properties of human and rodent skeletal muscle.
      The findings suggest that following as little as 5-6 in space there are deficits
      in both human and rodent motor capacity, strength, and endurance properties of
      skeletal muscle. The reduced strength is associated, in part, with a reduction in
      muscle mass as reflected in smaller cross-sectional areas of both fast- and slow
      twitch fibers. Available evidence in animal models suggests that slow-twitch
      fibers are more sensitive to the atrophying process. Accompanying the atrophy is
      a transformation of slow to fast protein phenotype involving myosin heavy chain
      and sarcoplasmic reticulum protein isoforms. These transformations appear to be
      regulated, in part, by pretranslational processes. Data on the oxidative capacity
      of rodent skeletal muscle suggest a bias toward preferential utilization of
      carbohydrate as the primary substrate. These collective findings suggest that
      skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity
      for the normal expression of protein mass and slow phenotype. Future studies need
      to focus on elucidating the mechanisms associated with the atrophy response, as
      well as identifying suitable exercise and other countermeasures capable of
      preserving the structural and functional integrity of skeletal muscle.

PMID- 8871909
TI  - Neuroendocrine and immune system responses with spaceflights.
AB  - Despite the fact that the first human was in space during 1961 and individuals
      have existed in a microgravity environment for more than a year, there are
      limited spaceflight data available on the responses of the neuroendocrine and
      immune systems. Because of mutual interactions between these respective
      integrative systems, it is inappropriate to assume that the responses of one have
      no impact on functions of the other. Blood and plasma volume consistently
      decrease with spaceflight; hence, blood endocrine and immune constituents will be
      modified by both gravitational and measurement influences. The majority of the in
      flight data relates to endocrine responses that influence fluids and electrolytes
      during the first month in space. Adrenocorticotropin (ACTH), aldosterone, and
      anti-diuretic hormone (ADH) appear to be elevated with little change in the
      atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased
      ADH variability with elevations in angiotensin and cortisol. Although post-flight
      results are influenced by reentry and recovery events, ACTH and ADH appear to be
      consistently elevated with variable results being reported for the other
      hormones. Limited in-flight data on insulin and growth hormone levels suggest
      they are not elevated to counteract the loss in muscle mass. Post-flight results
      from short- and long-term flights indicate that thyroxine and insulin are
      increased while growth hormone exhibits minimal change. In-flight parathyroid
      hormone (PTH) levels are variable for several weeks after which they remain
      elevated. Post-flight PTH was increased on missions that lasted either 7 or 237
      d, whereas calcitonin concentrations were increased after 1 wk but decreased
      after longer flights. Leukocytes are elevated in flights of various durations
      because of an increase in neutrophils. The majority of post-flights data
      indicates immunoglobulin concentrations are not significantly changed from pre
      flight measurements. However, the numbers of T-lymphocytes and natural killer
      cells are decreased with post-flight conditions. Of the lymphokines, interleukin
      2 production, lymphocyte responsiveness, and the activity of natural killer cells
      are consistently reduced post-flight. Limited head-down tilt (HDT) data suggest
      it is an effective simulation model for microgravity investigations.
      Neuroendocrine and pharmacological countermeasures are virtually nonexistent and
      should become high priority items for future research. Although exercise has the
      potential to be an effective countermeasure for various neuroendocrine-immune
      responses in microgravity, this concept must be tested before flights to Mars are
      scheduled.

PMID- 8871910
TI  - Exercise as a countermeasure for physiological adaptation to prolonged
      spaceflight.
AB  - Exercise represents the primary countermeasure used during spaceflight to
      maintain or restore maximal aerobic capacity (VO2max), musculoskeletal structure,
      and orthostatic function. However, no single exercise or combination of
      prescriptions has proven entirely effective in restoring cardiovascular and
      musculoskeletal functions to preflight levels following prolonged spaceflight. As
      human spaceflight exposures increase in duration, assessment and development of
      various effective exercise-based protective procedures become paramount. This
      must involve improvement in specific countermeasure prescription as well as
      development of additional approaches that will allow space travelers greater
      flexibility and medical safety during long flights. Effective exercise
      prescription will be based on identification of basic physiological stimuli that
      maintain normal function in terrestrial gravity and understanding of how specific
      combinations of exercise characteristics e.g., duration, frequency, intensity,
      mode) can mimic these stimuli and affect the overall process of adaptation to
      microgravity. This can be accomplished only with greater emphasis of research on
      ground-based experiments. Future attention must be directed to improving exercise
      compliance while minimizing both crew time and the impact of the exercise on life
      support resources.

PMID- 8871911
TI  - Adaptation of the hypothalamopituitary adrenal axis to chronic exercise stress in
      humans.
AB  - Repeated acute or chronic exposure to a particular stress results in adaptation
      whereby the hypothalamopituitary adrenal (HPS) axis becomes less responsive to
      subsequent or continued exposure to that particular stress. To investigate the
      adaptive changes that occur in the HPA axis in response to chronic stress in
      humans, we studied the effect of chronic exercise stress on basal activity of the
      HPA axis in six highly trained male ultramarathon athletes and six healthy male
      controls matched for body mass index. After 3-5 of abstention from intense
      physical activity, the subjects were admitted to a metabolic study ward at 1600
      h. Peripheral blood was sampled initially at 0300 h, at 20-min intervals from
      0400 to 0900 h, hourly from 0900 to 1200 h, and then every 2 h from 1200 to 1600
      h. A 24-h urine collection was completed during the admission. Peripheral blood
      adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. Plasma and
      urinary cortisol were measured by enzyme-linked immunoassay. Plasma and injury
      cortisol were measured by enzyme-linked immunosorbent assay (ELISA). Plasma ACTH
      and cortisol levels showed the expected diurnal change in athletes and control
      subjects (P = 0.00001). However, the early morning ACTH and cortisol surge
      occurred earlier in the athletes than in the controls (P = 0.026). Plasma ACTH
      levels were significantly higher in the athletes than in the control subjects (P
      = 0.0026). There was, however, no significant overall difference in plasma
      cortisol levels between the athletes and the control subjects, and urinary
      excretion of free cortisol was similar in the two groups. These data show that
      intense physical training leads to adaptive changes in basal HPA function,
      including a phase shift and increased pituitary in basal HPA function, including
      a phase shift and increased pituitary ACTH secretion, but also blunting of the
      adrenal cortisol response.

PMID- 8871912
TI  - Repeatability and relative validity of two physical activity questionnaires in
      elderly women.
AB  - In a population of 33 women aged 51-71 yr, two physical activity questionnaires
      (a modified Baecke questionnaire and the pre-EPIC questionnaire) were tested for
      repeatability (5 and 11 months). For assessment of relative validity, the
      questionnaires were compared with a physical activity diary (12 d) as the main
      reference method, a single 24-h Caltrac accelerometer score, and energy intake
      estimated from a 24-h dietary recall repeated 12 times. Repeatability of the
      questionnaires at 5 months was 0.82 (Baecke) and 0.42 (pre-EPIC), at 11 months
      0.73 and 0.60, respectively. Correlation with the activity diary was 0.51 for the
      Baecke and 0.64 for the pre-EPIC questionnaire. Correlation with the Caltrac was
      0.22 for both questionnaires, and with energy intake -0.21 and 0.43,
      respectively. Factor analysis suggested that the questionnaires and the diary
      measured a common aspect of activity, which could be interpreted as "reported
      normal physical activity." Women who reported sweating or breathlessness during
      the past week scored significantly higher only on the Baecke questionnaire. It
      was concluded that the two questionnaires seemed to be able to rank older women
      according to physical activity in epidemiological studies.

PMID- 8871913
TI  - Validity of selected physical activity questions in white Seventh-day Adventists
      and non-Adventists.
AB  - The validity and reliability of selected physical activity questions were
      assessed in both Seventh-day Adventist (N = 131) and non-Adventist (N = 101)
      study groups. Vigorous activity questions similar to those used by others and new
      questions that measured moderate and light activities were included. Validation
      was external, comparing questionnaire data with treadmill exercise time, resting
      heart rate, and body mass index (kg.m-2), and internal, comparing data with other
      similar questions. Both Adventist and non-Adventist males showed significant age
      adjusted correlations between treadmill time and a "Run-Walk-Jog Index" (R =
      0.28, R = 0.48, respectively). These correlations increased substantially when
      restricting analysis to exercise speeds exceeding 3 mph (R = 0.39, R = 0.71,
      respectively). Frequency of sweating and a vigorous physical activity index also
      correlated significantly with treadmill time in males. Correlations were
      generally weaker in females. Moderate- and light-intensity questions were not
      correlated with physical fitness. Internal correlations R = 0.50-0.78) between
      the above three vigorous activity questions were significant in all groups, and
      correlations (R = 0.14-0.60) for light and moderate activity questions were also
      documented. Test-retest reliability coefficients were high for vigorous activity
      questions (R = 0.48-0.85) and for one set of moderate activity questions (R =
      0.43-0.75). No important differences in validity and reliability were found
      between Adventist and non-Adventists, but the validity of vigorous activity
      measures was generally weaker in females.

PMID- 8871914
TI  - Whole-body hyperhydration in endurance-trained males determined using
      radionuclide dilution.
AB  - Despite evidence of hypervolemia following endurance training, there is little
      information regarding corresponding extravascular fluid volumes. Quantification
      of such volumes relies upon radionuclide dilution methods, previously hampered by
      the loss of plasma albumin. It was our purpose to measure human body-fluid
      distribution in eight endurance-trained males, using a simultaneous radionuclide
      dilution technique, incorporating radioiodinated serum fibronogen (RISF). Fluid
      distribution was measured on three occasions, using 2 microCi of RISF, 8 microCi
      of 51 Cr-labeled erythrocytes, and 20 microCi of Na82Br and 450 microCi of 3H2O;
      to measure PV, erythrocyte (RCV), extracellular (ECFV), and total-body water
      (TBW) volumes, respectively. Respective volume means, standard deviations, and
      coefficients of variation were: 46.6 (+/- 4.9; 8.44%), 33.3 (+/- 2.9; 3.89%),
      258.1 (+/- 12.1; 4.93%), and 654.2 (+/- 13.4; 3.24%) ml.kg-1. The incorporation
      of RISF provided a reliable modification to previous methods, and revealed a body
      fluid expansion in endurance-trained males. It was concluded that such subjects
      were hyperhydrated, possessing proportionately expanded fluid volumes throughout
      both intravascular and extravascular spaces. This was attributed to training
      history and accompanying reductions in adiposity.

PMID- 8871915
TI  - The heart of the senior oarsman: an echocardiographic evaluation.
AB  - We evaluated left ventricular mass and function in 15 oarsmen aged 78 (65-82) yr
      (median and range) and in 15 sedentary males aged 72 (65-81) yr by 2-D and M-mode
      echocardiography and cycle ergometry. The weekly time spent exercising among the
      oarsmen was 6 (2-18) h and two of the oarsmen were former national and
      international champions. The two groups of subjects had similar weight, height,
      and resting blood pressure. The oarsmen reached a maximal work rate of 142 (117
      174) vs 113 (75-150) W for the sedentary group (P < 0.01). The internal diameters
      of the left ventricle were not significantly different, but the septum and
      posterior wall thicknesses were larger in the oarsmen (11 (8-20) vs 9 (7-11) mm,
      and 9 (8-13) vs 8 (7-19) mm, respectively, P < 0.023). Thus, the left ventricular
      mass index of the oarsmen was 19% larger (127 (101-284) vs 103 (74-134) g.m-2, P
      < 0.01). Also, the systolic function appeared to be superior in the oarsmen as
      the fractional shortening was 0.45 (0.28-0.55) vs 0.36 (0.18-0.49) in the
      controls (P < 0.05). In conclusion, we found that long-term rowing in the senior
      oarsman is associated with enlarged myocardial wall thickness, a normal systolic
      function, and a high work capacity.

PMID- 8871916
TI  - Gender effect on the relationship of time limit at 100% VO2max with other
      bioenergetic characteristics.
AB  - The aim of this study was to investigate the influence of gender on the possible
      contribution of tlim at Va max (minimal speed that elicits VO2max) in performance
      speeds. The male and female elite middle-distance runners had similar performance
      (IAAF scores). Fourteen female and fifteen male (25.2 +/- 3.6 and 25.1 +/- 4.2 yr
      old; VO2max = 63.2 +/- 4.2 and 77.7 +/- 6.4 ml.kg-1 min-1; Va max = 17.3 +/- 0.7
      and 20.8 +/- 1.1 km.h-1, respectively) performed three exercise tests on a
      treadmill (3 degrees slope) within a 2-wk period: an incremental test to
      determine VO2max, Va max and the velocity at the onset of blood lactate
      accumulation (VOBLA); an exhaustive constant velocity test to determine tlim at
      Va max; and an exhaustive constant velocity test at 110% Va max to determine the
      accumulated oxygen deficit (AOD). There were no effects of gender, i.e., no
      significant differences were observed between female and male for tlim at Va max
      (421 +/- 129 vs 367 +/- 118 s respectively; P = 0.24), VOBLA as % Va max (88.4 +/
      2.7 vs 90.4 3% of Va max; P = 0.07), AOD (40.1 +/- 14.9 vs 48.9 +/- 21.3
      ml.O2.kg-1; P = 0.22), running economy at the same absolute speed, i.e., 14 km.h
      1 (53.4 +/- 2.6 vs 52.7 +/- 4.1 ml.O2.min-1.kg-1; P = 0.64) nor for gross oxygen
      cost of running (CR) at the same relative velocity (75% Va max) (0.214 +/- 0.001
      vs 0.214 +/- 0.002 ml.O2.kg-1.m-1; P = 0.94). However, an effect of gender was
      found on the relationship between the bioenergetic parameters and performance.
      For male, v1500 was predicted by Va max, VOBLA, tlim at 110% of Va max, and CR
      (R2 = 0.96). For female, no bioenergetic parameters were strongly correlated with
      v1500 m. The inverse relationship found between Va max and tlim at Va max in
      previous literature was confirmed by the 29 runners in this study and for the
      subset of male only.

PMID- 8871917
TI  - Influence of water run training on the maintenance of aerobic performance.
AB  - The purpose of this study was to examine the effect of a 6-wk deep water running
      program on the maintenance of cardiorespiratory performance (VO2max, ventilatory
      threshold, running economy); metabolic measurements of blood glucose, blood
      lactate, and plasma norepinephrine; and body composition. Sixteen trained male
      runners (VO2max = 58.6 +/- 3.6 ml.kg-1.min-1) were assigned to one of two groups
      matched by VO2max, treadmill run (R) or water run (WR). Subjects participated in
      their respective training programs, which consisted of workouts of a) 30 min at
      90-100% VO2max and b) 60 min at 70-75% VO2max alternated daily for 5 d.wk-1.
      Following 6 wk of workouts, no significant intra- or intergroup differences were
      observed for treadmill VO2max for R (pre = 58.4 +/- 2.3, post = 60.1 +/- 3.6
      ml.kg-1.min) and WR (pre = 58.7 +/- 4.7, post = 59.6 +/- 5.4 ml.kg-1.min-1).
      Similarly, ventilatory threshold was unaltered in R (pre = 47.5 +/- 1.8, post =
      48.2 +/- 3.3 ml.kg-1.min-1) and WR (pre = 46.5 +/- 6.4, post = 47.4 +/- 6.7 ml.kg
      1.min-1), nor were there any changes in running economy in R (pre = 48.4 +/- 2.3,
      post = 48.9 +/- 2.0 ml.kg-1.min-1 at 255 m.min-1) and WR (pre = 51.8 +/- 2.0,
      post = 48.9 +/- 2.2 ml.kg-1.min-1 at 255 m.min-1). No significant differences
      were observed within or between groups for maximal blood glucose, blood lactate,
      and plasma norepinephrine concentration as well as for body composition indices.
      It was concluded that deep water running may serve as an effective training
      alternative to landbased running for the maintenance of aerobic performance for
      up to 6 wk in trained endurance athletes.

PMID- 8871918
TI  - Reported alcohol use and behavior in long-distance runners.
AB  - Because alcohol may impair sports performance, we hypothesized there would be
      less drinking in serious recreational runners. We used mailed questionnaires to
      examine drinking patterns (2-wk quantity/frequency), scores on modified versions
      of the Michigan Alcoholism Screening Test (brief MAST [BMAST], short MAST
      [SMAST]), and parental history of problem drinking in 397 men and 144 women
      runners participating in a 20-mile race, compared with a nonexercising control
      population of 138 men and 119 women. A subset of 188 pairs (104 men, 84 women)
      were matched for gender, age, educational level, and marital status. We used chi
      square analysis, paired t-test, and ANOVA. Male gender, running, and a family
      history for problem drinking predicted increased total alcohol consumption. We
      found that male runners (vs male controls) drank more 14.2 +/- 19.6 vs 5.4 +/-
      7.6 drinks.wk-2, P = 0.004) and felt guilty about their drinking (26.6% vs 13.8%,
      P < 0.01). Men and women runners reported more occasions of drinking than matched
      controls (2.8 +/- 2.7 vs 2.0 +/- 2.3.wk-2, P = 0.004). Runners with scores on the
      BMAST (> or = 6) or SMAST (> or = 3) suggestive of a history of problem drinking
      drank less than controls with a similar score. Contrary to our hypothesis,
      running is associated with increased alcohol consumption, except in those who
      report a history of problem alcohol behavior.

PMID- 8871919
TI  - Accuracy of five electronic pedometers for measuring distance walked.
AB  - This is a three-part study that examined the accuracy of five brands of
      electronic pedometers (Freestyle Pacer, Eddie Bauer, L.L. Bean, Yamax, and
      Accusplit) under a variety of different conditions. In Part I, 20 subjects walked
      a 4.88-km sidewalk course while wearing two devices of the same brand (on the
      left and right side of the body) for each of five different trials. There were
      significant differences among pedometers (P < 0.05), with the Yamax, Pacer, and
      Accusplit approximating the actual distance more closely than the other models.
      The Yamax pedometers showed close agreement, but the left and right Pacer
      pedometers differed significantly (P = 0.0003) and the Accusplit displayed a
      similar trend (P = 0.0657). In Part II, the effects of walking surface on
      pedometer accuracy were examined. Ten of the original subjects completed an
      additional five trials around a 400-m rubberized outdoor track. The devices
      showed similar values for sidewalk and track surfaces. In Part III, the effects
      of walking speed on pedometer accuracy were examined. Ten different subjects
      walked on a treadmill at various speeds (54, 67, 80, 94, and 107 m.min-1).
      Pedometers that displayed both distance and number of steps were examined. The
      Yamax was more accurate than the Pacer and Eddie Bauer at slow-to-moderate speeds
      (P < 0.05), though no significant differences were seen at the fastest speed.
      While there are variations among brands in terms of accuracy, electronic
      pedometers may prove useful in recording walking activities in free-living
      populations.

PMID- 8871920
TI  - Histologic findings in postcryosurgical prostatic biopsies.
AB  - The increasing use of cryosurgical ablation of the prostate for prostatic
      carcinoma necessitates that surgical pathologists be aware of the cryosurgically
      induced histologic changes in the prostate. Twenty-one patients at our
      institution underwent prostatic cryosurgery, and 17 subsequently had follow-up
      biopsies. The Gleason combined scores ascribed to the original tumors were 4 (two
      patients), 5 (six patients), 6 (seven patients), 7 (one patient), and 8 (one
      patient). Histologic examination revealed residual carcinoma (four patients, with
      Gleason combined scores of 4, 5, 6, and 8), necrosis (all 17 patients),
      hyalinization (nine patients), fibrosis (nine patients), granulomatous
      inflammation (three patients), foci of calcification (eight patients), squamous
      metaplasia (four patients), transitional metaplasia (two patients), hemosiderin
      deposition (six patients), edema (two patients), bacterial colonization (one
      patient), and hemorrhage (one patient). The grade of residual carcinoma in all
      four patients was identical with the grade assigned before the cryosurgical
      ablation. The stroma surrounding the residual tumor did not display any
      postcryosurgical histologic changes, and we postulate that these areas were not
      adequately frozen. In conclusion, prostatic cryotherapy induces a variety of
      histologic changes in normal and diseased tissue.

PMID- 8871921
TI  - Neutrophil-rich Ki-1-positive anaplastic large cell lymphoma presenting as a
      testicular mass.
AB  - Ki-1-positive large cell lymphoma is an uncommon subtype of lymphoma that may
      involve lymph nodes as well as a variety of extranodal locations. To the best of
      our knowledge, the occurrence of such a tumor in the testis has not been
      previously documented. We report a case of Ki-1-positive large cell anaplastic
      lymphoma presenting as a testicular mass in a 56-year old Saudi.
      Immunohistochemical staining revealed positive staining for Ki-1 and UCHL-1,
      which indicated a T-cell phenotype. This was further confirmed by polymerase
      chain reaction analysis, which demonstrated a monoclonal cell population with
      rearrangement of gamma T-cell receptor. Another interesting morphologic feature
      was the presence of large numbers of neutrophils throughout the tumor. Similar
      neutrophil-rich lymphomas have been described recently as a special subtype of Ki
      1-positive anaplastic large cell lymphoma.

PMID- 8871922
TI  - Occult micropapillary carcinoma associated with benign follicular thyroid disease
      and unrelated thyroid neoplasms.
AB  - Surgically resected thyroids from 425 patients with thyroid disease other than
      carcinoma of follicular cell derivation were thoroughly examined for occult
      micropapillary carcinoma (MPC). There were 317 cases of nodular hyperplasia, 36
      of thyroiditis, 44 follicular adenomas, and 28 others. Glands were sectioned at 2
      to 3-mm intervals and fixed in formalin. Every section was examined
      histologically. There were 71 cases (16.7%) of MPC containing 118 tumors. Among
      343 women, 51 (14.9%) had MPC; among 82 men, 20 (24.4%) had MPC. The average age
      of all of the patients was 46.9 years and of those with MPC, 50.5 years. The
      occurrence of MPC peaked between 40 and 70 years and declined in older patients.
      MPC was found in 8.9% of patients who underwent lobectomies, 10.8% who had
      hemithyroidectomies, and 24.1% of those who had total thyroidectomies. Logistic
      regression analysis revealed significant associations between the presence of MPC
      and the patient sex, age, and extent of surgery; in contrast, there was no
      association between the occurrence of MPC and the underlying thyroid disease.
      These data indicate that MPC is present in up to 24.1% of thyroids removed for
      unrelated thyroid disease. The predominance of this lesion in men is in striking
      contrast to the occurrence of clinically significant thyroid cancer. This
      suggests that the initiation of carcinogenesis is not sexually dimorphic, whereas
      promoters of tumor growth are. A rational management of this common disease
      awaits the results of careful controlled trials.

PMID- 8871923
TI  - Epithelioid hemangioma of small tubular bones: a report of three cases, two of
      them associated with pregnancy.
AB  - We report three cases of epithelioid hemangioma of small tubular bones in women
      aged 20, 24, and 50 years. In two patients, the tumor appeared during or shortly
      after pregnancy. We studied clinical data, radiographs, and hematoxylin- and
      eosin-stained slides, and we performed immunohistochemical and flow cytometric
      DNA analysis. The tumor was in distal phalanges of the fingers in two patients
      and in metatarsal bone in one. Cortical bone destruction with infiltration of the
      surrounding soft tissue was seen in all of the patients. Light microscopic
      examination showed characteristic morphology, highlighted by epithelioid
      endothelial cells with different degrees of vasoformativity.
      Immunohistochemically, the epithelioid cells showed strong positive reaction for
      Factor VIII in all three patients, for CD31 in two, and for CD34 in one. Ulex
      europaeus antigen and keratins were negative. Laminin and collagen IV delineated
      innumerable predominantly abortive vascular structures, which were encircled by
      cells that presumably were pericytic and that were positive for smooth muscle
      actin. A relatively high degree of immunostaining for proliferating cell nuclear
      antigen and Ki67 contrasted with the low mitotic rate and low percentage of cells
      in S phase. Progesterone and estrogen receptors were negative. Epithelioid
      hemangiomas of small tubular bones are rare lesions that are characterized by
      early bone destruction and infiltration of soft tissues. Their association with
      pregnancy may be fortuitous; if any gestation-related proliferative stimulation
      exists, it does not seem to be mediated through steroid receptors.

PMID- 8871924
TI  - The case for parallel classification of biliary tract and pancreatic neoplasms.
AB  - Most primary epithelial neoplasms found in the intrahepatic and extrahepatic
      biliary tracts and the pancreas have similar histologic appearances. The degree
      of similarity of tumor types is greater than is commonly appreciated and extends
      to rare neoplasms. It has been suggested that parallel classifications could be
      used for tumors arising in these sites. However, significant differences in terms
      used to denote histologically identical neoplasms are found in the current World
      Health Organization (WHO) classification of biliary tract tumors and the new WHO
      classification of exocrine pancreatic neoplasms. Mutations of oncogenes and
      abnormalities of tumor suppressor genes found in ductal adenocarcinomas from the
      two sites are also similar, although they have somewhat different frequencies.
      These histologic and molecular similarities provide strong support for the use of
      parallel descriptive diagnostic terminology for neoplasms arising in the pancreas
      and the biliary tract. The revised WHO classification of exocrine pancreatic
      neoplasms accommodates most types of biliary tract neoplasms and provides a new
      basis for standardization of nomenclature.

PMID- 8871925
TI  - Detection of von Hippel-Lindau disease gene mutations in paraffin-embedded
      sporadic renal cell carcinoma specimens.
AB  - The von Hippel-Lindau (VHL) disease gene on chromosome 3p25.5 has been cloned and
      shown to be mutated in the germline DNA of patients with VHL disease. In
      addition, approximately 60% of sporadic renal cell carcinomas (RCCs) have been
      shown to have a VHL gene mutation in fresh frozen tumor tissue and tumor-derived
      cell lines. The objective of this study was to test whether VHL gene mutations
      could be detected in archival sporadic RCC cases. We studied three sporadic RCCs,
      two oncocytomas, and the corresponding adjacent normal renal parenchyma by
      polymerase chain reaction and single-strand conformation polymorphism analysis
      using paraffin-embedded, formalin-fixed material. Tumor and normal tissue were
      microdissected from eosin-stained 5-microns-thick histologic sections. Mutations
      in exon 2 of the VHL gene were detected in all three of the sporadic RCCs but
      were not observed in the matched normal renal tissues or in the two oncocytomas
      tested. The mutations were identical to those detected in tumor cell lines from
      the same patients. This report represents the first detection of VHL gene
      mutations in sporadic RCCs in archival, paraffin-embedded tissue. A high
      percentage of sporadic RCCs show VHL gene mutations in fresh frozen tissue but
      the availability of frozen material is limited, so the evaluation of archival
      tumors for similar mutations should prove useful in future RCC studies.
      Furthermore, the results suggest that the genetic events leading to the
      development of clinically benign renal oncocytoma may differ from those leading
      to malignant RCC.

PMID- 8871926
TI  - Spiraled collagen in the major blood vessels.
AB  - Vascular spiraled collagen (SC) was investigated by electron microscopic and
      immunohistochemical means in anatomically corresponding pairs of the major
      arteries and veins under normal or morbid condition in 45 autopsies. The
      frequency and extent of SC were marked in the veins, compared with the arteries.
      SC was particularly noted in the left anterior descending coronary artery beneath
      a myocardial bridge, which had been free from atherosclerosis, in contrast to
      those sites in the nonbridged vessel, which is always involved by
      atherosclerosis. SC was similarly conspicuous in the normal great saphenous vein,
      when compared with the phlebosclerotic vessel. The diameters of SC increased with
      the age of the patient. Immunohistochemical examination of matrix
      metalloproteinases (MMP-1, -2, and -3) revealed significant expression of MMP-1
      in smooth muscle cells (SMCs) of vascular wall in which SCs was abundant, whereas
      tissue inhibitor of MMP-1 was absent in SMCs regardless of the presence of SC.
      Together with the frequent spatial association of SC with degraded elastic fibers
      and contractile-type SMCs, the present results indicate that whereas normal
      collagen fibrils are unilaterally degraded at extracellular spaces by
      interstitial enzymes and are possibly followed by their assembly to form SC, SMCs
      remain stationary in cell activities during aging. We conclude that SC is formed
      preferentially in the normal blood vessels through a physiologic degradation of
      normal collagen fibrils.

PMID- 8871927
TI  - A nonradioactive method for rapid and sensitive detection of polymerase chain
      reaction products by use of bromo-deoxyuridine.
AB  - A highly sensitive and nonradioactive method that allows for rapid detection of
      polymerase chain reaction (PCR) products, without the need for hybridization with
      oligonucleotide probes, is described. In this method, a 410-bp sequence of the
      human respiratory syncytial virus nucleocapsid cDNA was amplified by PCR in the
      presence of bromo-deoxyuridine-triphosphate, an analog of deoxythymidine
      triphosphate. After agarose gel electrophoresis and Southern blotting, the PCR
      product was directly identified by immunoenzyme-chemiluminescent reaction after
      binding with an antibromodeoxyuridine antibody. The results show that
      substitution of bromo-deoxyuridine-triphosphate for deoxythymidine-triphosphate
      does not affect the efficiency of PCR, and as low as one copy-equivalent of the
      target DNA sequence could be detected within 2 hours, whereas it required 1 to 5
      days to reach comparable sensitivity level after hybridization with a 32P-labeled
      oligonucleotide probe and autoradiography. Compared with the use of digoxygenin
      11-deoxyuridine-triphosphate, the sensitivity of detection was 100-fold higher
      with the use of Bromo-deoxyuridine-triphosphate. When applied to the diagnosis by
      use of reverse transcription-PCR of respiratory syncytial virus infections in
      nasopharyngeal washes from children with symptoms of acute upper respiratory
      tract infection, the current method detected respiratory syncytial virus genome
      in 29 of 100 specimens, and there was a complete concordance with the results of
      hybridization of reverse transcription-PCR products by use of a radiolabeled
      oligonucleotide probe. Thus, in addition to its rapidity of detection and high
      sensitivity, this method provides safety of use and can be readily applied to the
      clinical diagnosis of viral respiratory tract infections.

PMID- 8871928
TI  - Expression of the CD44 cell adhesion molecule in urinary bladder transitional
      cell carcinoma.
AB  - CD44 cell adhesion molecule (PgP-1, ECM III, Hermes antigen) is a polymorphic
      integral membrane glycoprotein associated with cell matrix adhesion, lymphocyte
      activation, recirculation, and homing. CD44 expression has been reported in in
      malignant lymphoma and in a variety of epithelial human cancers but has not been
      studied as a prognostic marker in urinary bladder transitional cell carcinoma.
      CD44s (standard 85- to 95-kDa macromolecule) expression was measured by
      qualitative and image analysis-quantitated immunohistochemical techniques using
      the A3D8 monoclonal antibody. CD44v6 (a splice variant exon of CD44s) expression
      was measured by qualitative immunohistochemical techniques using the 2F10
      monoclonal antibody. The results of CD44s and CD44v6 expression were compared
      with tumor grade, pathologic stage, and DNA content analysis on Feulgen-stained
      tissue sections in 44 cases of urinary bladder transitional cell carcinoma. The
      mean percentage-positive area of staining intensity for CD44s expression in Grade
      1 tumors was 61%, compared with 30% for the Grade 3 tumors (P < 0.001). Non
      invasive tumors featured a 59%-positive area of staining intensity, compared with
      the 30% staining percentage for the deeply invasive tumors (P < 0.001). There was
      significant correlation of aneuploid DNA content with loss of CD44s staining (P <
      0.05). The staining results for CD44v6 paralleled those for the CD44s, with a
      significant loss of staining in high-grade and high-stage aggressive tumors in
      comparison with the low-grade nonaggressive tumors (P < 0.01). In urinary bladder
      transitional cell carcinoma, CD44s and CD44v6 expression parallels that for other
      cell adhesion molecules, such as E-cadherin, that feature a significant
      progressive loss of immunoreactivity in association with tumor dedifferentiation,
      advancing pathologic stage, and abnormal DNA content.

PMID- 8871929
TI  - Calcofluor white stain for the detection of Pneumocystis carinii in
      transbronchial lung biopsy specimens: a study of 68 cases.
AB  - Calcofluor white (CFW), a chemofluorescent agent, has proven effective in the
      recognition of Pneumocystis carinii cysts in respiratory fluids and secretions.
      However, its usefulness in the recognition of P. carinii cysts in tissue
      preparations has not been established. We studied 68 formalin-fixed, paraffin
      embedded, transbronchial tissue biopsy specimens from individuals seropositive
      for the human immunodeficiency virus and stained them with the CFW stain and the
      conventional Gomori methenamine silver (GMS) stain to determine the concordance
      rate of the two stains. CFW-positive specimens showed light peripheral staining
      and a unique double parenthesis-like structure near the center of the cysts.
      Thirty-six (52.9%) of the 68 specimens were CFW and GMS positive, whereas 27
      (39.7%) of the specimens were negative by both techniques, yielding a concordance
      rate of 92.6%. Five (7.4%) of the 68 specimens showed disparate results, and, of
      these, four (5.9%) were CFW positive and GMS negative, whereas one (1.5%) was CFW
      negative and GMS positive. We conclude that the CFW stain is suitable and useful
      for the demonstration of P. carinii cysts in tissue preparations.

PMID- 8871930
TI  - Recommendations for reporting resected neoplasms of the kidney. Association of
      Directors of Anatomic and Surgical Pathology.

PMID- 8871931
TI  - Correspondence re: Moran C, Rosado-De-Christenson M, Suster S: thymolipoma:
      clinicopathologic review of 33 cases. Mod Pathol 8:741, 1995.

PMID- 8871932
TI  - Correspondence re: Brandwein M, Nuovo G, Ramer M, Orlowski W, Miller L: Epstein
      Barr virus reactivation in hairy leukoplakia. Mod Pathol 9:298, 1996.

PMID- 8871933
TI  - Correspondence re: Nucci MR, Genest DR, Tate JE, Sparks CK, Crum CP:
      pseudobowenoid vulvar change: untreated condyloma acuminatum. Mod Pathol 9:375,
      1996.

PMID- 8871934
TI  - Correspondence re: Nucci MR, Genest DR, Tate JE, Sparks CK, Crum CP:
      pseudobowenoid vulvar change: untreated condyloma acuminatum. Mod Pathol 9:375,
      1996.

PMID- 8871935
TI  - Correspondence re: Henson DE: is the meaning of science changing in the practice
      of medicine? Mod Pathol 9:353, 1996.

PMID- 8871936
TI  - Nicotinic receptors in the brain. Molecular biology, function, and therapeutics.
AB  - Although the psychological and physiological effects of nicotine have long
      suggested that nicotine exerts specific actions in the brain, the identification
      of neuronal nicotinic receptors (nAChRs) only began in the past few years with
      the development of molecular genetics. It is now clear that neuronal nAChRs form
      a family of highly heterogenous receptor subtypes, as evidenced by the number of
      genes encoding nAChR subunits, the diversity of immunopurified receptor proteins,
      and the multiple functional types of ligand-gated ion channels. Neuronal nAChRs
      have discrete localizations within the brain, and are involved in modulating
      neuronal firing and transmitter release. Cumulative evidence from animal and
      human studies indicates that nicotinic systems play a major role in higher
      cognitive functions and dysfunctions. In particular, the loss of cortical nAChRs
      is a neuro-chemical hallmark of Alzheimer (AD) and Parkinson (PD) diseases. In
      addition, nicotine improves memory and attention in Ad and PD. Our recent studies
      using electrophysiological biochemical and behavioral approaches suggest that the
      prefrontal cortex is a major target site for the cognitive actions of nicotine.

PMID- 8871937
TI  - Species differences in the generation of reactive oxygen species by microglia.
AB  - Although a variety of potential sources for reactive oxygen species (ROS) exist
      in the CNS, brain macrophages, i.e., the microglia, generate large quantities of
      these reactive species, particularly in response to injury or inflammatory
      signals. In order to understand how microglia contribute to changes in oxidative
      status of the CNS and how this might related to disease states, such as Alzheimer
      disease (AD), we have examined the regulation of superoxide anion and nitric
      oxide production from rodent and human microglia. Our results indicate that
      microglia from all species we have studied release superoxide anion, but produce
      significantly different amounts in response to the same activating agents.
      Species differences are also found in the ability to generate nitric oxide (NO).
      In particular, mouse microglia generate large quantities of NO when stimulated,
      but human and hamster microglia do not produce measurable amounts under the same
      stimulation conditions. These species differences are important to consider when
      modeling human disease processes from rodent studies.

PMID- 8871938
TI  - The heat shock/oxidative stress connection. Relevance to Alzheimer disease.
AB  - Involvement of free-radical oxidations in the aging process has been a topic of
      interest since Harman's original contribution. Because of the close association
      between aging and Alzheimer disease (AD) and the qualitative similarity in the
      neuropathology of both conditions, it has been proposed by many investigators
      that oxidative stress may be important in Ad. If such modality of injury was
      indeed involved, one should expect to find markers of oxidation and heat shock
      (since free radicals are key mediators of heat-shock induction) in brains of
      patients with AD. In fact, several studies documented abnormal expression of
      antioxidant enzymes and heat-shock proteins (HSP) along with other markers of
      oxidation in AD brains. We showed that abnormally expressed antioxidant enzymes
      are topographically associated with senile plaques and neurofibrillary tangles,
      and that the activity of these enzymes is (contrary to what one would expect)
      markedly reduced. These findings have recently been confirmed by other
      investigators. Despite a large amount of evidence that suggests an association
      between oxidative stress and the pathogenesis of AD, it is not yet known whether
      oxidative stress is a cause or consequence of the disorder. Future research
      efforts regarding the oxidative stress hypothesis of AD should include attempts
      at generating AD pathology by oxidative means in laboratory animals, determining
      the role and integrity of the heat-shock response in AD, as well as that of
      various antioxidant systems, growth factors, and hormones with antioxidant and
      neuroprotective properties.

PMID- 8871939
TI  - Oxidative stress and age-related neuronal deficits.
AB  - Research from our laboratory has indicated that the loss of sensitivity that
      occurs in several receptor systems as a function of age may be an index of an
      increasing inability to respond to oxidative stress (OS). This loss occurs
      partially as a result of altered signal transduction (ST). Assessments have
      involved determining the nature of age-related reductions in oxotremorine
      enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal
      slices. Using this model, we have found that 1. Reductions can be restored with
      in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha
      phenylnitrone (PBN); 2. Decrements in DA release induced by NO or H2O2 from
      striatal slices from both young and old animals could be restored with alpha
      tocopherol or PBN; 3. ST decrements, such as those seen in aging, could be
      induced with radiation exposure; and 4. Pre-incubation of the striatal slices
      with cholesterol decreased subsequent deleterious effects of NO or OH. on DA
      release. Thus, cholesterol, which increases in neuronal membranes as a function
      of age, may function as a potent antioxidant and protectant against neuronal
      damage. These results suggest that therapeutic efforts to restore cognitive
      deficits in aging and age-related disease might begin with antioxidant reversal
      of ST decrements.

PMID- 8871940
TI  - Oxidative posttranslational modifications in Alzheimer disease. A possible
      pathogenic role in the formation of senile plaques and neurofibrillary tangles.
AB  - The distinctive pathological lesions of Alzheimer disease (AD), senile plaques,
      and neurofibrillary tangles comprise aggregates of insoluble fibrillar protein.
      We and other investigators recently demonstrated that several mechanisms related
      to oxidative stress and free-radical reactions could play a crucial role in the
      pathogenesis of AD and, specifically, in the formation of senile plaques and
      neurofibrillary tangles (NFT).

PMID- 8871941
TI  - Radical changes in beta-amyloid form and function.
AB  - A growing body of evidence supports the nucleation hypothesis of fibrillar
      amyloid formation. In this article, it is hypothesized that the fibrils formed
      with human A beta, rodent A beta, and a mixture of the two peptides may form
      nearly identical physical structures with clearly different biological
      activities. Data is reported supporting the concept that a specific "strain" of
      nucleation seed could impart a new structure on a growing amyloid fibril, thereby
      changing its biological activity. The data that the biological activities of
      specific prion strains have a basis in strain-specific structure have been
      supported experimentally.

PMID- 8871942
TI  - AMPA-selective glutamate receptor subtype immunoreactivity in the hippocampal
      dentate gyrus of patients with Alzheimer disease. Evidence for hippocampal
      plasticity.
AB  - Immunocytochemical techniques were employed in order to examine the distribution
      and relative intensity of immunolabeling of the alpha-amino-3-hydroxy-5-methyl-4
      isoaxolepropionate (AMPA) receptor subunits GluR1 and GluR2/3 within the
      hippocampal formation of patients with Alzheimer disease (AD). Within sectors of
      the hippocampus that are particularly vulnerable to AD pathology (i.e., CA1,
      subiculum), we observed a variable loss of GluR1 and GluR2/3 immunolabeling
      correlating with the extent of cell loss and neurofibrillary pathology. In
      contrast, in less vulnerable sectors of the hippocampus (i.e., CA2/3, dentate
      gyrus), the intensity of immunolabeling was markedly increased in AD cases,
      particularly in the molecular and polymorphic layers of the dentate gyrus.
      Importantly, these latter regions correspond to termination zones of
      glutamatergic perforant pathway axons and mossy fiber collaterals, respectively.
      The increase in immunolabeling within these projection fields is hypothesized to
      occur in response to the deafferentation of selected glutamatergic pathways, and
      suggests a critical role for AMPA receptor subunits in hippocampal plasticity.

PMID- 8871943
TI  - Hippocampal damage and cytoskeletal disruption resulting from impaired energy
      metabolism. Implications for Alzheimer disease.
AB  - To determine if impaired energy metabolism might contribute to some aspects of
      Alzheimer disease (AD), including the vulnerability of the CA1 region of the
      hippocampal formation and the altered cytoskeleton evident in neurofibrillary
      tangles, we examined the effects of metabolic poisons on neuronal damage and
      cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection
      of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death,
      particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but
      sparing of axonal gamma. MK-801 (a noncompetitive NMDA receptor antagonist) did
      not atentuate the lesions produced by intrahippocampal injection of malonate. MK
      801, however, was effective against intrastriatal malonate. Acute systemic 3-NP
      resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the
      hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but
      sparing of gamma. The neuronal loss in CA1 was delayed as compared to striatum.
      Chronic intraventricular infusion of 3-NP produced a different pattern of
      neuronal damage. Loss of gamma-1 immuno-reactivity was observed in CA3 and CA1 s.
      orients, whereas MAP2 immunostaining was preserved. These results demonstrate
      that chronic and acute administration of metabolic inhibitors produce distinct
      patterns of neuronal damage and cytoskeletal disruption. The results further
      suggest a differential involvement of the NMDA receptor in malonate-induced
      neuronal damage in striatum as compared to the hippocampus. The pattern of
      neuronal damage and cytoskeletal disruption observed following acute metabolic
      impairment resembled some aspects of neurofibrillary pathology in AD, but did not
      result in gamma hyperphosphorylation.

PMID- 8871944
TI  - Immunogenetic studies in autism and related disorders.
AB  - The major histocompatibility complex comprises a number of genes that control the
      function and regulation of the immune system. One of these genes, the C4B gene,
      encodes a product that is involved in eliminating pathogens such as viruses and
      bacteria from the body. We previously reported that a deficient form of the C4B
      gene, termed the C4B null allele (no C4B protein produced) had an increased
      frequently in autism. In this study we attempted to confirm the increased
      incidence of the C4B null allele in autism and investigated the presence of a C4B
      null allele in two other childhood disorders, attention-deficit hyperactivity
      disorder and dyslexia (reading disability). In addition, we explored the
      relationship of autism to the DR beta 1 gene, a gene located close to the C4B in
      autism. We confirmed the finding of an increased frequency of the C4B null allele
      in autism and found that the related disorders also had an increased frequency of
      this null allele. In addition, two alleles of the DR beta 1 gene also had
      significantly increased representation in the autistic subjects.

PMID- 8871945
TI  - Inflammation and Alzheimer disease.
AB  - Inflammatory mechanisms are active in patients with Alzheimer disease. Serum
      elevations of acute phase proteins such as alpha 1-antichymotrypsin, along with
      deposition of inflammatory cytokines in the brain, suggest a "cerebral acute
      phase response" contributing to amyloid deposition and tissue destruction.
      Activated microglia possessing HLA-DR surface markers accumulate around amyloid
      plaques. The complement cascade leads to generation of the membrane attack
      complex, which may directly damage neuronal membranes. This growing body of
      evidence suggests that empirical trials of anti-inflammatory drugs are now
      appropriate to test the hypothesis that suppression of these mechanisms will slow
      the rate of progression of Alzheimer disease. Several drugs useful in the
      treatment of rheumatic diseases are candidates for study in Alzheimer disease,
      including glucocorticoids, antimalarial drugs, and colchicine. Pilot studies of
      the synthetic glucocorticoid prednisone indicate that treatment with a moderate
      dose is well tolerated in patients with Alzheimer disease, and suppresses serum
      levels of acute phase proteins. Based on this experience, a multicenter parallel
      design placebo-controlled trial has been initiated with Alzheimer's Disease
      Cooperative Study to determine whether treatment with prednisone can slow the
      rate of progression of Alzheimer disease.

PMID- 8871946
TI  - Microglial cerebrospinal fluid antibodies. Significance for Alzheimer disease.
AB  - Hallmark lesions of Alzheimer disease (AD) are filled with reactive
      immunocompetent microglia, suggesting that immunological aderrations may
      participate in the pathophysiology of this disorder. If immune-mediated processes
      are closely linked to neuronal breakdown, it would be or importance to have a
      reliable means to detect these processes. Cerebrospinal fluid (CSF) antibodies
      are discussed as such potential sources. The seredipitous use of the developing
      rat central nervous system (CNS) unexpectedly demonstrated that some AD CSF
      recognize amoeboid microglial cells. Similarly, AD CSF specifically stains
      activated microglia and neural macrophages in experimentally induced lesions. A
      cell-culture technique is described that allows rapid screening of CSF
      antibodies. Examination of CSF from a diversified dementia population revealed
      that AD CSF, in contrast to other dementia CSF, displayed remarkable selectivity
      toward microglial cells. Cortical biopsies from patients suspected to have AD
      were incubated with the patient's own CSF and that of confirmed AD patients. Both
      CSF samples recognized microglial cells in the cortical biopsy. AD CSF microglial
      antibodies appear to be significant in view of the increasing association between
      microglia and neuro degenerative processes in AD. These findings add further
      support to the concept that inflammation and similar immune mechanisms may
      contribute to to AD pathogenesis.

PMID- 8871947
TI  - Biochemical and cognitive studies of apolipoprotein-E-deficient mice.
AB  - Apolipoprotein-E-deficient mice provide a useful model system for studying the
      role of apolipoprotein E (apoE) in brain function. In the present study, we
      characterized the cholinergic function of these mice and the extent of
      phosphorylation of their cytoskeletal protein tau. Morris water maze tasks
      revealed deficits in working memory that were accompanied by a specific decrease
      in hippocampal and cortical choline acetyltransferase activities. Immunoblot
      experiments utilizing native and dephosphorylated tau and antibodies directed
      against specific phosphorylated and unphosphorylated tau epitopes revealed that
      tau of the apoE-deficient mice is hyperphosphorylated. These results show that
      apoE-deficient mice have cognitive cholinergic and cytoskeletal derangements and
      point out the importance of this model for studying the role of apoE in neuronal
      function.

PMID- 8871948
TI  - Immune-activation model in Alzheimer disease.
AB  - About 10 years ago, we implicated immune factors in the pathophysiology of
      Alzheimer disease (AD), the hypothesis being that AD may be an immunologically
      derived systemic disease, but clinical effects confined primarily to the brain.
      We originally hypothesized that an immune basis of the disease may involve faulty
      immune regulation and autoimmunity. As described here, the activation of
      immunoregulatory T-lymphocytes with CD8 phenotype may be important in the
      immunopathogenesis of the disease.

PMID- 8871949
TI  - Level of mental impairment in the Jamaican elderly and the issues of screening
      levels, caregiving, support systems, carepersons, and female burden.
AB  - Jamaica, although a developing country, has an aging population and is facing the
      many issues confronting aging. A community-based study using the Folstein
      minimental screening tool identified 2.3% of the over-60 population as severely
      impaired and 11.8% as questionable. The family was identified as the main source
      of support, and female relatives the main carepersons. Mentally impaired persons
      were less likely than physically impaired persons not to have a support system or
      careperson needed.

PMID- 8871950
TI  - Alzheimer disease. Outreach to the African American community.
AB  - In an attempt to determine the risks for and kinds of dementia most prevalent
      among the African American population, the Alzheimer's Disease Research Center at
      the University of Pittsburgh developed a community satellite program specifically
      targeting the African American and historically medically underserved communities
      in Allegheny County, PA. The primary mission of the Alzheimer Outreach Center
      (AOC) was to increase the awareness of Ad among the targeted population. The
      number on nonwhite patients participating in the studies at ADRC increased from 2
      to 16% in the first year of the program. In May 195, the AOC became a permanent
      ADRC program.

PMID- 8871951
TI  - Possible regulation of high-affinity glutamate uptake in synaptosomes of normal
      and epileptic mice.
AB  - Glutamate (Glu) uptake is the primary mechanism for its removal from the synapse.
      In genetic audiogenic seizures (AGS), Glu uptake is elevated prior to the
      appearance of seizures. Increased Glu uptake is also observed in synaptosomes
      from normal mice preincubated with lithium or nitroarginine, an NO synthase
      inhibitor. Pertussis and cholera toxins cause a marked reduction in Glu uptake.
      In contrast, neither lithium nor nitroarginine affected Glu uptake by
      synaptosomes from genetic epileptic mice. Arachidonic acid inhibits Glu uptake,
      whereas synaptosomes from epileptic mouse brain appear to be more sensitive to
      arachidonic acid as indicated by a shift of the inhibition curve to the left.
      These observations are indicative of the possible regulation of Glu uptake by
      second messengers and its alteration in genetic epilepsy.

PMID- 8871952
TI  - Neurotropic viruses and Alzheimer disease. Interaction of herpes simplex type 1
      virus and apolipoprotein E in the etiology of the disease.
AB  - Infectious agents have been proposed as possible etiological factors in sporadic
      cases of Alzheimer disease (AD), herpes simplex type 1 virus (HSV1) being a
      likely candidate. We have detected laten HSV1 in brain from AD patients and from
      aged normal individuals, using polymerase chain reaction (PCR), in the regions
      most affected in the disease. In contrast, we have not detected another
      neurotropic herpes virus, varicella zoster (VZV), in any brains. We have
      postulated that HSV1 reactivates periodically, and that a host or viral
      characteristic determines the degree of damage caused by the resulting acute
      infection-with much greater damage in the case of AD patients. We have therefore
      examined a host factor-the apolipoprotein E (apoE) genotype, since the E4 allele
      is a known risk factor in the disease. We have found that the risk of developing
      AD is much greater in those who are HSV1-positive in brain and who possess an
      apoE4 allele than for those with only one of these factors.

PMID- 8871953
TI  - Mechanisms of neuronal cell death. An overview.
AB  - Neuronal cell death is both a vital component of the embryo-genesis of the
      nervous system and forms the basis of all neurodegenerative diseases. This
      overview explores the fundamental mechanisms underlying neuronal cell death at a
      cellular and molecular level. The significance of the mode of neuronal death is
      compared with respect to physiological (developmental) and pathological neuronal
      loss.

PMID- 8871954
TI  - Neurodegeneration in Alzheimer disease. Is apoptosis involved?
AB  - Alzheimer disease (AD), the most common dementia of the elderly, results from a
      significant loss of neuronal cells in brain regions important in memory and
      cognition. Several lines of evidence suggest that the A beta peptide is directly
      responsible for some of this neuronal cell death. We review recent evidence from
      in vitro toxicity and immunohistochemical studies that suggest some of the cell
      loss in AD is the result of apoptosis.

PMID- 8871955
TI  - Apoptosis-mediated neurotoxicity induced by beta-amyloid and PrP fragments.
AB  - The neurotoxic activity of beta-amyloid (beta A) and prion protein (PrP)
      fragments contributed to the hypothesis concerning a causal role of amyloid
      deposits in Alzheimer disease (AD) and in prion-related encephalopathies. In this
      study, we investigated some aspects of the molecular mechanisms associated with
      neurotoxic activity of synthetic peptides homologous to beta A (beta 25-35) or
      PrP (PrP106-126) fragments. Chronic (5-7 d) exposure to both peptides induced
      neuronal death by apoptosis, as suggested by biochemical and morphological
      analysis. The apoptotic mechanism was confirmed by ultrastructural examination.
      The intracellular cascade of events activated by peptides was investigated by
      Northern blot and PCR analysis of expression of early genes (c-fos, c-jun, c-myc)
      and other proteins (p53, SGP-2 bcl-2, HSP70, Ich-1) potentially involved in
      apoptosis. With the exception of bcl-2 mRNA decrease and a slight increase of SGP
      2 in PrP106-126-treated cells, no consistent alterations of these mRNA
      expressions were found in neuronal cells exposed to beta 25-35 or PrP106-126.
      Furthermore, we synthesized amidated homologs of both peptides with low
      amyloidogenic activity to test directly the relationship between amyloid fibrils
      and cell death. The neurotoxicity exhibited by PrP106-126-NH2 was similar to that
      observed with original peptide, whereas the amidation of beta 25-35 partially
      reduced the neurotoxicity of this peptide.

PMID- 8871956
TI  - Effects of chronic infusion of nerve growth factor (NGF) in AF64A-lesioned rats.
AB  - We report here the behavioral and biochemical recovery induced by the nerve
      growth factor (NGF) administration in AF64A-treated rats. Retention in the
      passive avoidance test was affected by lesion but it was significantly improved
      after the NGF treatment. Similar results were observed in the performance during
      the Morris water maze (MWM) task. Remarkable losses in the ChAT activity were
      detected in some brain regions from lesioned rats. The NGF-induced alleviation of
      choline acetyltransferase (ChAT) activity losses and cognitive functions suggest
      a trophic and protective action on the remaining cholinergic neurons after the
      lesion. Thus NGF therapy could be considered as a possibility mainly in the early
      course of Alzheimer disease.

PMID- 8871957
TI  - Effects of chronic infusion of nerve growth factor (NGF) in rats with nucleus
      basalis magnocellularis lesion.
AB  - We attempted to evaluate the effects of bilateral injection of ibotenic acid (IA)
      into the nucleus basalis magnocellularis (nbm) of rats as well as the potential
      recovery mediated by the infusion of nerve growth factor (NGF). The lesion caused
      an impairment of learning and memory processes. Also, a severe depletion of
      choline acetyl transferase activity was detected in cortical areas. After the NGF
      administration, a significant reversion of these functional changes was observed.
      Thus, IA-lesioned rats might serve as a model for the evaluation of neurotrophic
      factors actions on basal forebrain damaged neurons.

PMID- 8871958
TI  - Modulation of glial cell signaling by adenosine and pharmacological
      reinforcement. A neuroprotective strategy?
AB  - In view of the increasing evidence that a pathological glial activation plays a
      significant role in the development of neurodegenerative diseases, we
      investigated the underlying molecular signaling as a possible target for the
      pharmacological therapy. Here, we are particularly focusing on the endogenous
      modulation of the CA2+ and cyclic nucleotide-dependent signaling by the
      nucleoside adenosine and its reinforcement by the xanthine derivative
      propentofylline (PPF). As an experimental model, we used cultured rat microglial
      cells and astrocytes that are immature, show a high proliferation rate, and
      resemble in several aspects pathologically activated glial cells. A prolonged
      increase of the cellular cAMP level favored the differentiation of cultured
      astrocytes and associated properties required for the physiological nerve cell
      function. On the other hand a strengthening of the cyclic nucleotide-dependent
      signaling inhibited potentially neurotoxic properties of cultured microglial
      cells. Similar effects were obtained by treatment with propentofylline, which
      mimicked modulatory adenosine effects and increased the intracellular level of
      cAMP and cGMP. Such a pharmacological glial cell conditioning, obtained by
      modifying the strength and the timing of these second messengers, may provide a
      therapy of neurodegenerative diseases in which a pathological activation of
      microglial cells and astrocytes is discussed to playa pathogenic role.

PMID- 8871959
TI  - Ischemic neuronal damage. How does mild hypothermia modulate it?
AB  - The significance of mild hypothermia as a therapeutic measure for ischemic brain
      damage is presented on the basis of different experimental results. An
      extracellular glutamate surge, a sustained activation of N-methyl-D-aspartate
      (NMDA) receptors, and an enhancement of DNA binding activity to transcription
      factor AP-1, all being key items directly linked to excitotoxic neuronal damage,
      are deeply affected by slightly lowering temperature (mild hypothermia [MH]). The
      cellular mechanism of MH seems rather nonspecific but tends to collectively
      involve these key items rendering neurons resistant to ischemic damage. Clinical
      application of MH should be a great challenge to relieve deadly effects on
      central neurons.

PMID- 8871960
TI  - Chemoattraction of sensory neuron growth cones by diffusible concentration
      gradients of acetylcholine.
AB  - Axon guidance cues are critical for the development and repair of both the
      central and peripheral nervous systems. These cues serve to help select the
      pathways taken by axon growth cones, by attracting or repulsing them. During
      development and following injury to the adult peripheral nervous system, neurons
      must extend processes, often over long distances, through a variety of cellular
      environments composed of innervated and uninnervated cells, to find, recognize,
      and synapse on their appropriate targets. The responsibility for recognizing and
      responding to the extensive number of cues that are encountered as axons elongate
      falls on the growth cones at the tip of the elongating axons. Cajal (1928)
      proposed that denervated target cells release diffusible factors that assist in
      orienting the direction of out-growth of peripheral axons. However, it is only
      relatively recently that experiments to identify the molecules responsible for
      serving this function, and the molecular mechanisms by which they function, have
      begun to bear fruit. Gradients of both substrate-bound and diffusible factors
      have now been shown to play critical roles in directing axon outgrowth. The
      present experiments were aimed at determining whether the neurotransmitter
      acetylcholine (ACh) can act as a chemoattractant for adult sensory neuron growth
      cones.

PMID- 8871961
TI  - Laminins in the adult and aged brain.
AB  - Only recently have we become aware of the diversity of laminins in adult brain.
      In vascular basement membranes, the expression of at least five laminin chains
      has been demonstrated, suggesting the presence of several laminin variants.
      Recent ultrastructural evidence for heterogeneity of laminin expression in
      vascular basement membranes is an exciting finding, and points to structural and
      functional diversity of the basement membranes around cerebral blood vessels.
      Neuronal laminin-like immunoreactivity in the adult brain is a consistent
      observation, but does not fit well in the current understanding of the physiology
      and biochemistry of the heterotrimeric laminins. Nevertheless, the unique
      localization of putative neuronal laminins warrants their further
      characterization. The structure and function of laminins produced by reactive
      astrocytes in the lesioned adult brain and that seen in the brains of Alzheimer
      disease (AD) patients are not yet resolved. The possibility that these laminins
      play an important role in the CNS response to injury and pathophysiology of AD is
      expected to be a fruitful investigation. The next decade should see very
      significant advances in the characterization of brain laminins and, hopefully, in
      the elucidation of functional correlates to the structural diversity of laminins
      in brain.

PMID- 8871962
TI  - Neurotrophin receptors and selective loss of cholinergic neurons in Alzheimer
      disease.
AB  - The most consistent neuropathological finding in Alzheimer disease (AD) is the
      loss of cholinergic neurons of the nucleus basalis of Meynert (NbM). Using
      immunohistochemistry, we have previously shown that cholinergic neurons located
      in the ventral striatum were affected, whereas those of the caudate nucleus,
      putamen, and mesencephalon were spared. Since cholinergic neurons that degenerate
      in AD are sensitive to NGF and those that are spared are not, it has been
      hypothesized that the loss of neurotrophins receptors may play a role in the
      death of cholinergic neurons in AD. Using immunohistochemistry, we have detected
      the presence of TrkA on most cholinergic neurons from the NbM, on some from those
      of the striatum, but not on those of the mesencephalon in the human brain. In AD
      patients, the number of neurons that expressed TrkA was markedly decreased in the
      NbM very likely as a consequence of cholinergic neuronal loss. In the striatum,
      despite the loss of high-affinity NGF binding previously reported, no loss of
      TrkA was observed. Taken together, these results suggest a decreased expression
      of NGF receptors on the striatal cholinergic neurons in AD. This loss may
      contribute, when it reaches a crucial threshold, to the death of cholinergic
      neurons occurring in AD.

PMID- 8871963
TI  - NGF in experimental models of Parkinson disease.
AB  - We have now applied the enzyme immunoassay using anti-NGF monoclonal antibody
      (MAb) 27/21 and a blocking test validating the specificity of the
      immunoreactivity for NGF in serum samples to examine NGF levels in normal rat
      sera, hemiparkinsonian rat sera, normal monkey sera, and MPTP-treated monkey
      sera. The levels of NGF in treated animals showed reductions when compared with
      serum from normal animals. The NGF level alterations observed in lesioned animals
      and in human parkinsonian patients evidence a relationship between this
      neurotrophic factor and the neurodegenerative changes observed in Parkinson
      disease (PD).

PMID- 8871964
TI  - Neural networks in the study of the brain.
AB  - Neural networks are models of the brain and have been used within Artificial
      Intelligence to provide alternative explanations to the symbolic explanations of
      cognition in which one assumes that an intelligent system has certain explicit
      representation of some aspect of the world and uses these in intelligent
      behavior. Obviously, if neural networks are indeed good models of the brain, and
      give a satisfactory account of cognition, then they could be a valuable tool to
      neuroscientists. This article gives a brief overview of the various neural
      network models, and critically reviews their status as models of the brain and of
      cognition.

PMID- 8871965
TI  - Retroviruses and schizophrenia in Jamaica.
AB  - Reports of an 18-fold higher incidence of schizophrenia among second-generation
      Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon
      called "an epidemic of schizophrenia," with the inference that a novel virus,
      likely to be perinatally transmitted, was a possible etiological agent. This
      intriguing observation led us to explore a possible link with human T-cell
      lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in
      the Caribbean Island, is perinatally transmitted, known to be neuropathogenic,
      and the cause of a chronic myelopathy (tropical spastic paraparesis/HTLV-I
      associated myelopathy. We therefore examined inpatients as the Bellevue Mental
      Hospital, Kingston, Jamaica and did standard serological tests for retroviruses
      HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and
      DSM III-R criteria for schizophrenia. Our results produced important negative
      data, since the seropositivity rates for HTLV-I, the most likely pathogen, were
      no greater than the seropositivity range for HTLV-I carriers in this island
      population, indicating the HTLV-1 and the other retroviruses tested do not play a
      primary etiological role in Jamaican schizophrenics.

PMID- 8871966
TI  - How do neurons degenerate in transmissible spongiform encephalopathies?
AB  - Neuroaxonal dystrophy is a feature of neuronal degeneration encountered in all
      subacute spongiform virus encephalopathies including scrapie and Creutzfeldt
      Jakob disease (CJD). By immunohistochemical techniques, the accumulation of 200
      kDa neurofilament protein was demonstrated in affected neurites in human CJD.
      These neurites exhibited the ultrastructural features of dystrophic neurites
      encountered in other neurodegenerative disorders, particularly Alzheimer's
      disease. These findings support the hypothesis that impairment of slow axoplasmic
      transport is a common pathogenetic mechanism for CJD and many other
      neurodegenerative conditions.

PMID- 8871967
TI  - Laboratory of Caribbean Brain Research Organization in the decade of the brain
      midpoint. Results in reaching behavior--interferences of subcortical motor
      centers, neurotransmitter blocking and brain function modeling.
AB  - CARIBRO was founded in response to the United Nations declaration that the 1990s
      be designated the Decade of the Brain. The Program of Action is: 1. Annual
      meetings; 2. Training courses of the Caribbean School of Neurosciences; 3.
      Network scientific programs; 4. Fellowship programs; and 5. Dissemination of
      information on neuroscience. In the same program, a CARIBRO Laboratory was
      created in one of the Medical Faculties of Havana with the aim to teach students
      from the Caribbean in neuroscience research. As part of this program, we have
      been working in lateralized motor functions. Preliminary results in rats show
      that reaching acquisition allows classification of the animals as right-handed
      (40%), left-handed (40%), and ambidextrous (20%). Electrolytic lesion of caudate
      nucleus or amygdala impairs lateralized response. Contralateral lesions increase
      reaching attempts. Ipsilateral lesions to the preferred forepaw do not affect the
      reaction. The results remain the same 10, 20, and 90 d after the interference.
      Pharmacological experiments showed that trihexiphenidil (0.1 mg/kg i.p.) induced
      handedness reversion in 50% if the animals, whereas haloperidol (1 mg/kg i.p.)
      produced immobility, tremor, and autonomic symptoms. This effect remained the
      same in young as well as in old animals. We are also working on mathematical
      modelation. In this sense, preliminary reports about a model for synaptic
      modification in the framework of the Fukushima hypothesis is discussed.

PMID- 8871968
TI  - Psychopathology of white mentally ill immigrants to Jamaica.
AB  - OBJECT: To test the hypothesis that white immigrants to a predominantly black
      country have a different pattern of psychopathology from the native population.
      METHOD: The psychopathology (DSM III-R) of white immigrants to Jamaica seen in
      the author's private practice between 1979 and 1990 was compared with the
      psychopathology of a control sample of native Jamaicans matched with the
      immigrant sample for age, sex, and social class. RESULTS: There was no
      statistical difference in the major diagnoses mood disorder (35%), anxiety states
      (27%), and schizophrenia (20%) between the immigrant and control groups. White
      immigrants to this black country did not develop schizophrenia at higher rates
      than the native born. White mentally ill immigrants to Jamaica move into social
      class positions at a significantly higher level (p < 0.005) than those of their
      parents with whom they grew up in their home country. This was significantly
      different (p < 0.005) from their Jamaican controls. Two case studies are
      presented to illustrate these findings. CONCLUSIONS: The political/economic
      situation which exists in black postcolonial countries like Jamaica provides a
      protective social environment for white immigrants, which buffers them from the
      etiological conditions that engender schizophrenia in immigrants to other
      countries with predominantly white populations.

PMID- 8871969
TI  - Monoclonal antibody affinities of structurally related modified nucleosides.
AB  - A scale of relative affinities of a series of 2'-deoxycytidine and cytidine (CD)
      derivatives was established based on the data of cross-reactivities of these
      compounds as well as the displacements obtained from a competitive ELISA. No
      correlation could be established between the nucleosides modifying structures and
      the affinities. This can be explained by the possibilities of the modifying
      structures of intra- and intermolecular nonimmunospecific interactions owing to
      their degree of functionalization.

PMID- 8871970
TI  - Neuroimmunological findings in Guillain Barre syndrome, multiple sclerosis, and
      idiopathic polyneuropathies.
AB  - It is essential to know how the immune system acts in different neurological
      diseases, some of which are not very well known or are unknown. IgG and albumin
      were simultaneously quantified in serum and cerebrospinal fluid (CSF) of 47
      patients with Guillain Barre Syndrome (GSB), 5 patients with multiple sclerosis
      (MS), and 14 patients with idiopathic polyneuropathies (IP). IgG local synthesis
      was observed in all patients, except in patients with IP. These patients showed a
      decrease in cerebrospinal fluid (CSF) flow.

PMID- 8871971
TI  - Novel mitochondrial proteins and decreased intrinsic activity of cytochrome-c
      oxidase. Characteristics of swayback disease in sheep.
AB  - Swayback disease (SD), a fatal neurological disorder affecting lambs and kids, is
      characterized by abnormal mitochondria and low cytochrome-c oxidase activity. The
      cytochrome-c oxidase content and activity and the protein composition of
      mitochondria isolated from the brains of SD lambs were investigated. Difference
      spectra analysis indicated that the cytochrome-c oxidase content of mitochondria
      from SD animals was lower than normal, and electrophoresis showed that when
      compared to mitochondria from normal animals, lipid-depleted mitochondria from SD
      lambs had a different protein composition, particularly, in the 40-55 kDa region.
      Polarographic studies, using cytochrome-c as substrate, confirmed low intrinsic
      activity of cytochrome-c oxidase within the mitochondria of SD lambs. These
      studies also showed that at low ionic strength, such mitochondria did not yield
      the expected characteristic biphasic Eadie-Hofstee plots.

PMID- 8871972
TI  - Neural factors influence the degeneration of muscle fibers in the chelae of
      snapping shrimps.
AB  - The asymmetric pincer and snapper claws in the snapping shrimp differ in external
      morphology and musculature. The snapper is a massive claw used for displays and
      defense; the pincer is small and slender, used for feeding and burrowing. The
      snapper has only slow muscle fibers; the pincer has both slow and fast. Removal
      or denervation of the snapper claw induces transformation of the contralateral
      pincer to a snapper type of claw at the subsequent molt. A removed claw
      regenerates as a pincer type, as long as the innervation of the remaining claw is
      intact. Fast muscle fibers, found exclusively in the pincer claw, normally
      degenerate completely within 10 d after the moult, which transforms the pincer to
      a snapper. Morphological transformation of the pincer following removal of the
      snapper claw can occur even if the pincer claw is denervated. Denervation of the
      pincer, however, delays degeneration of the fast fibers, increasing the estimated
      half-time of muscle degeneration, for 4.4 +/- 0.2 to 19.5 +/- 0.8. d after the
      transforming moult. Neural influences therefore are involved both in the
      determination of the morphology of the claw and in the induction of degenerative
      changes during the remodeling of an existing claw.

PMID- 8871974
TI  - Childhood sleep disorders.
AB  - Sleep problems in children may differ in various ways from analogous problems in
      the adult. This is less because of neurophysiologic differences between the two
      groups than it is because of the child's greater level of dependency. Young
      children make few decisions on their own and, as a result, parent-child
      interactions become connected intimately to the child's sleep process at bedtime
      and throughout the night. Parental desires and expectations are at least as
      important as those of the child in determining the pattern of sleep that follows.
      Such interactions are most important when it comes to understanding causes of
      sleeplessness in the young child, and only by appreciating these interactions can
      the clinician serve a useful role in helping the family to understand and improve
      a young child's problematic sleep patterns.

PMID- 8871975
TI  - Insomnia.
AB  - The series of cases presented here should illustrate that the complaint "I can't
      sleep" is deceptively simple. The clinician must be prepared to gather
      information from many disparate aspects of the patient's history and present
      circumstances. Diagnostic considerations are complicated further by the
      significant night-to-night variation in the manifestations of the insomnia. Too
      often, the result of this hidden complexity is a tendency either to prescribe
      hypnotic drugs as a first intervention or to give signals to patients with
      insomnia that not much can be done and that difficulty sleeping is simply a fact
      of life. The sleep log can help to bring order to the jumble of insomniac
      experiences. It leads both the clinician and patient away from assigning too much
      weight to a specific instance, instead allowing more general patterns to be
      discerned. As order is created out of the factors contributing to the insomnia, a
      treatment plan can be designed that goes beyond mere symptomatic treatment.

PMID- 8871976
TI  - Narcolepsy.
AB  - Narcolepsy is among the leading causes of excessive daytime sleepiness and is the
      most common neurologic cause. Its classic form--narcolepsy with cataplexy--is a
      distinct neurologic disease with characteristic clinical and paraclinical
      findings. The history, epidemiology, clinical picture, pathophysiology, cause,
      diagnosis, and treatment, both pharmacologic and nonpharmacologic, are discussed
      in detail.

PMID- 8871977
TI  - Idiopathic hypersomnia.
AB  - Idiopathic hypersomnia is not as well delineated as narcolepsy and its history is
      much more recent. There are at least two forms of the disorder: (1) a
      polysymptomatic form, characterized by excessive daytime sleepiness, nocturnal
      sleep of abnormally long duration, and signs of sleep drunkenness on awakening,
      and (2) a monosymptomatic form that manifests only by excessive daytime
      sleepiness. The most widely used laboratory procedures are nocturnal
      polysomnographic recording following by an MSLT demonstrating a mean sleep
      latency of less than 10 minutes. At least in the polysymptomatic form, however,
      continuous polysomnography on an ad lib protocol deserves to be performed to
      catch the abnormally long major sleep episode and the long unrefreshing naps.
      Idiopathic hypersomnia is probably one of the most overdiagnosed sleep disorders.
      Several other disorders must be excluded before the diagnosis can be considered
      conclusive. Treatment of idiopathic hypersomnia relies on stimulants, which are
      frequently less effective and less well tolerated than in narcolepsy.

PMID- 8871978
TI  - Obstructive sleep apnea and related disorders.
AB  - OSAS, a common cause of disrupted sleep and EDS, result from repetitive closure
      of the upper airway during sleep. It probably represents the most severe syndrome
      related to obstruction of the upper airway; less severe forms include UARS, a
      syndrome characterized by the need for increased effort to breath but no
      prominent apneas or hypopneas, and primary snoring. Initial clues to the presence
      of OSAS and related disorders are derived from the history and include loud
      snoring, EDS or insomnia, and witnessed apneas. Some patients, especially women,
      may complain mostly of tiredness or fatigue, and children may present with
      behavioral abnormalities. Obesity, a large neck circumference, and a crowded
      oropharynx are common on physical examination. Nonobese patients, in particular,
      often have retrognathia, a high-arched narrow palate, macroglossia, enlarged
      tonsils, temporomandibular joint abnormalities, or chronic nasal obstruction. The
      clinical suspicion of obstructed nocturnal breathing is confirmed by overnight
      polysomnography, and an MSLT may be used to assess sleepiness. Esophageal
      manometry during polysomnography facilitates diagnosis of UARS. Treatment most
      commonly consists of nasal CPAP or BPAP, although problems with compliance make
      surgical treatment preferable in some cases. Although UPPP eliminates sleep apnea
      only in a minority of patients, combining UPPP with maxillofacial procedures
      appears to improve outcomes. Other treatments such as the use of dental
      appliances or medications, weight loss, and positional therapy may be useful as
      adjunctive therapy for moderate to severe OSAS or as primary treatments for UARS
      or mild OSAS.

PMID- 8871979
TI  - Central sleep apnea.
AB  - A central sleep apnea is the absence of respiratory effect, and, thus, the
      absence of airflow during sleep. Central hypopnea, a related disorder, is also
      discussed. The sensory component of central sleep apnea; defects involving the
      integrative and executive neurons; non-neurologic causes of central sleep apneas,
      including chronic obstructive pulmonary disease and congestive heart failure;
      diagnosis; treatment; and other topics are reviewed in detail.

PMID- 8871980
TI  - Periodic limb movements and restless legs syndrome.
AB  - The criteria that characterize restless legs syndrome (RLS) and the differential
      diagnoses are discussed. Clinical signs include sleep disturbance, involuntary
      movements in sleep or wakefulness, a normal neurologic examination, a chronic
      clinical course, and, in some cases, a positive family history. Periodic limb
      movements during sleep, which also may occur as an isolated finding, may or may
      not cause frequent arousals or awakenings. Clinical diagnosis of idiopathic or
      symptomatic forms of RLS can be supported with polysomnography. Treatment of
      first choice consists of dopaminergic drugs or dopamine agonist followed by
      opioids or benzodiazepines.

PMID- 8871981
TI  - Disorders of the circadian sleep-wake cycle.
AB  - This article reviews several disorders of the circadian sleep-wake cycle,
      including delayed sleep phase syndrome, advanced sleep phase syndrome, non-24
      hour sleep-wake syndrome, irregular sleep-wake pattern, time zone change (jet
      lag) syndrome, and shift work sleep disorder. For each disorder, the cause,
      diagnostic work-up, and management are outlined.

PMID- 8871982
TI  - Job description hurtful to NPs.

PMID- 8871983
TI  - New guidelines on thyroid disease to improve diagnosis.

PMID- 8871984
TI  - Complementary therapies: an adjunct to traditional therapies.
AB  - Many Americans currently use complementary therapies, and there is a growing
      interest among others in trying these therapies in the future. Large amounts of
      money are being spent out of pocket on these measures. Health care provide these
      treatments to their patients. Research studies show that these methods are
      helpful for certain complaints. Many people turn to alternatives because
      traditional medical treatments do not always cure their ills. These alternatives
      are readily available to consumers who often lack knowledge of them. NPs are in a
      position to monitor and educate the public in their use. NPs, by the nature of
      their practice and theory base, are also in a position to incorporate some
      alternative therapies into their practices -- and they can start with some of the
      therapies described in this article. With further study, such therapies as
      Chinese herbs, homeopathy, massage, biofeedback, and therapeutic touch can be
      added.

PMID- 8871985
TI  - Physicians' and patients' knowledge and perceptions of the roles and functions of
      nurse practitioners.

PMID- 8871986
TI  - Prescriptive authority for Kentucky advanced registered nurse practitioners.

PMID- 8871987
TI  - Update on pharmacologic therapies for osteoporosis.
AB  - Osteoporosis is an increasingly prevalent chronic and debilitating disease. It is
      a metabolic disorder characterized by decreased bone mass that subsequently leads
      to bone fractures. Osteoporotic fractures occur most commonly in the hip, spine,
      distal radius, and ribs. Historically, pharmacologic options for the treatment of
      osteoporosis have been limited to hormone replacement therapy, vitamins, and
      mineral supplements. These previous treatments have been effective for many
      patients with osteoporosis. However, for many other patients, treatment with
      hormone replacement therapy, calcium, and vitamin D has been contraindicated or
      ineffective. Recently, several newly developed medications have become available
      for the treatment of osteoporosis in the United States. These new therapies have
      expanded the choices of pharmacologic options for primary health care providers
      and their patients. Pharmacologic therapy coupled with individualized diet,
      exercise, and fracture prevention counseling can help to decrease the severity
      and consequences of osteoporosis for growing numbers of Americans.

PMID- 8871988
TI  - Diagnosis and treatment of panic disorder and generalized anxiety in primary
      care.
AB  - Anxiety is one of the common yet underdiagnosed mental health problems of
      Americans; as many as 20% of people seeking primary care have symptoms of
      treatable anxiety disorders. Untreated anxiety increases costly visits to urgent
      care. Clinicians need to screen for anxiety among patients at risk who have
      physical symptoms such as shortness of breath, nervousness, gastrointestinal
      upset, palpitations, muscle aches, tension, and insomnia. Other diagnostic clues
      include restlessness, nervousness, phobias, trembling, fatigue, and shaking.
      Onset typically occurs in the 20s but may occur at any age. Symptoms of two
      anxiety disorders, generalized anxiety disorder (GAD) and panic disorder, are
      discussed. A combination of treatments including antidepressant and anxiolytic
      medications, behavioral treatments, education (e.g., self-management,
      relaxation), and counseling (e.g., coping strategies) have high success rates;
      psychiatric consultations or referrals are useful.

PMID- 8871989
TI  - An assessment tool to identify panic disorder.
AB  - Panic disorder is a psychiatric condition that is infrequently diagnosed
      correctly. People with untreated panic are most often seen in primary care
      settings. Panic is a debilitating condition that affects approximately 10% of the
      population and is eminently treatable when identified. Without treatment, clients
      are at risk for complications such as phobias, substance abuse, and depression.
      The purpose of this research study was to develop a valid, reliable tool to
      assist health care practitioners in identifying and assessing persons who have
      panic disorder. With the use of the Anxiety Inventory, information can be
      elicited to identify these people. In addition, data regarding the presence of
      phobias and depression and self-medication for any of the aforementioned
      behaviors can be collected. The tool also addresses any familial history of
      anxiety, panic attacks, depression, and drug and alcohol abuse. With the use of
      the Anxiety Inventory, practitioners can diagnose panic disorder in their clients
      and refer them for appropriate treatment.

PMID- 8871990
TI  - Wellness spirituality in the older adult. Assessment and intervention protocol.
AB  - Supporting the spiritual dimension of life is essential to high-level wellness
      and wholeness. It helps one respond to the potential fullness of life despite
      problems that arise from illness and longevity. However, health care providers
      frequently fail to inquire about spiritual well-being and thus fail to nurture
      the spirit. This oversight has especially strong consequences when health care
      providers treat older adults. This article defines wellness spirituality. It
      discusses clinical presentation of the conditions in life and illness that
      indicate that an aging client's spiritual well-being is being challenged.
      Wellness spirituality activities to consider with history taking, both within and
      outside the context of religion, are outlined. Management approaches are offered
      to support and restore aging client's ability to achieve spiritual well-being.
      The article also describes virtues clinicians must hold to create a spiritually
      nurturing environment in all settings. A protocol is offered as a clinical
      guideline for clinicians to use in their assessment and management of the
      wellness spirituality of older adults.

PMID- 8871992
TI  - 13-year-old female with imperforate hymen.
AB  - Imperforate hymen is a rare occurrence in younger women resulting in hydrocolpos
      and hydrometrocolpos. Though imperforate hymen may be diagnosed in infancy,
      females ages 9-15 years most often present with the problem. Imperforate hymen
      usually is a congenital anomaly, but has been reported as a result of sexual
      abuse. This case report reviews the presentation and treatment of a 13-year-old
      female with imperforate hymen.

PMID- 8871991
TI  - Primary care management of chronic musculoskeletal pain.
AB  - Chronic musculoskeletal pain, a common problem seen in the primary care setting,
      is often frustrating for both the patient and the clinician. Despite its
      prevalence, chronic pain is often poorly understood and inconsistently managed by
      health care providers. Unlike acute pain, chronic pain serves no biologic
      function and persists long after the tissue has healed from injury. Patients with
      chronic pain may become isolated from friends and family, lose their jobs, and
      develop depression. Nonpharmacologic techniques such as acupuncture, massage, and
      relaxation may be helpful to the patient with chronic pain. In addition to
      nonsteroidal antiinflammatory drugs, antidepressants and opioid analgesics are
      useful for treating chronic musculoskeletal pain. This article explains that
      pathophysiology of chronic pain, lists aspects of chronic pain that distinguish
      it from acute pain, and develops a general primary care plan for patients with
      chronic musculoskeletal pain.

PMID- 8871993
TI  - Haemophilus influenzae type b.

PMID- 8871994
TI  - Applying viral load measurements to HIV care.

PMID- 8871995
TI  - Nurse practitioner-performed procedures.

PMID- 8871996
TI  - Leaders and leadership: who are they and what is it?

PMID- 8871997
TI  - Emerging infectious diseases: nursing responses.

PMID- 8871998
TI  - Case management: a rich history of coordinating care to control costs.
AB  - The process of case management has been used to coordinate health and human
      services in the United States for more than a century. Throughout its history,
      case management has been practiced by a variety of disciplines, primarily nursing
      and the social service disciplines. Regardless of the degree of sophistication of
      the case management model or the discipline practicing case management,
      historically the goal has been the same--coordination of complex, fragmented
      services to meet the needs of the client while controlling the costs of services.
      As the health care industry continues to evolve during the managed care era, case
      management seems to be pervading all health care delivery systems as a means of
      dealing with the issues of access and quality while containing costs. The long
      history of case management provides a strong foundation for the refinement of
      case management systems to meet the needs of clients in the 1990s.

PMID- 8871999
TI  - The mother-headed single-parent family: a feminist critique of the nursing
      literature.

PMID- 8872000
TI  - Correcting misconceptions about pain assessment and use of opioid analgesics:
      educational strategies aimed at public concerns.

PMID- 8872001
TI  - NLRB v. Health Care & Retirement Corporation of America, Inc.: a challenge for
      the nursing profession.

PMID- 8872002
TI  - Women's health and managed care.

PMID- 8872003
TI  - Men researching women working.

PMID- 8872007
TI  - Uniparental disomy and genome imprinting: an overview.

PMID- 8872004
TI  - Genetic and molecular studies on Om, a locus controlling mouse preimplantation
      development.

PMID- 8872009
TI  - The search for molecular defects in genetic disease.

PMID- 8872011
TI  - An introduction to genomic imprinting and parent of origin effects.

PMID- 8872010
TI  - Embryologic development and monozygotic twinning.

PMID- 8872012
TI  - Tuberous sclerosis: between genetic and physical analysis.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder
      with extensive clinical variability. Present estimates of the prevalence of TSC
      suggest that it may exceed 1:6,000. New mutations are frequent, as about 2/3 of
      all cases are apparently sporadic. Locus heterogeneity has been established, with
      one gene on chromosome 9q34 (TSC1) and the other on chromosome 16p13.3 (TSC2).
      The majority of TSC2 mutations are probably subtle alterations. In some cases,
      somatic and germline mosaicism might be explanations for intrafamilial phenotype
      variation and apparent non penetrance. A role of the predicted protein product
      tuberin in growth suppression would be in agreement with allelic losses observed
      in tumors of TSC patients. Studies on tuberin using antibodies raised against
      various parts of the protein can be expected to provide insight into its normal
      and impaired function.

PMID- 8872013
TI  - Wiedman-Beckwith syndrome, tumorigenesis and imprinting.

PMID- 8872016
TI  - Multiple imprinted genes associated with Prader-Willi syndrome and location of an
      imprinting control element.

PMID- 8872018
TI  - Fragile X syndrome in humans and mice.

PMID- 8872020
TI  - Imprinting and transgenerational modulation of gene expression; human growth as a
      model.
AB  - It is proposed that transgenerational modulation of gene expression might be
      possible, if the metabolic response of the parent to some physiological or social
      stress modified imprint setting. Transcription regulators could theoretically
      mediate this process. The nature of imprinted genes poised, as it were, between a
      transcriptionally active and silent state, makes them good candidates for
      incorporation into the evolution of transgenerational adaption systems where
      coordinated changes in gene expression over the generations is a selective
      advantage. The coordination of human fetal (head) growth with the existing size
      of the mother's pelvis is suggested as just such a circumstance. The reduce birth
      weight of Dutch babies where their grandmothers suffered acute starvation in mid
      pregnancy, supports the notion of transgenerational adaption to nutrition, as
      does the secular change (increase) in child growth over the last century. The
      recent indication that there may be functional polymorphism in the imprinting of
      the human IGF2 and IGF2R genes suggests these ideas could be explored using
      association studies at the population and individual level.

PMID- 8872021
TI  - Medical and clinical genetics: their roots and challenge.

PMID- 8872022
TI  - A bird's eye view of human sex determination.

PMID- 8872024
TI  - Uniparental disomy and genomic imprinting in humans.

PMID- 8872025
TI  - Aneuploid correction and confined placental mosaicism.

PMID- 8872026
TI  - Combined molecular and cytogenetic analysis for the rapid diagnosis of fragile X
      syndrome.
AB  - The fragile X mutation is the result of an abnormal expansion of a CGG repeat
      sequence in the FMR-1 gene. Molecular techniques enable the detection of the
      mutation and also of the exact length of this DNA sequence, allowing the
      classification of the tested subjects as normal, carrier or affected. We propose
      a protocol of analysis that combines a method of non-radioactive PCR, Southern
      blotting and cytogenetic testing. This protocol can be used for screening
      programme of selected groups of mentally retarded individuals and for prevention
      studies in families at risk.

PMID- 8872027
TI  - Maternal uniparental disomy for chromosome 14.
AB  - A girl carrying a de novo balanced 13-14 robertsonian translocation showed a
      clinical phenotype with severe hypotonia, hyperextensible joints, frontal
      bossing, asymmetric face, no mental retardation, severe scoliosis and motor
      delay. In situ hybridization analysis on chromosome spreads revealed the presence
      of the two centromeres in the rearranged chromosomes. Molecular analysis on
      genomic DNA showed the presence in the proposita of two chromosomes 14 of
      maternal origin and no chromosome 14 from the father indicating a maternal
      monocentric uniparental disomy for chromosome 14 (mUPD14). Our patient shows
      several similarities with other reported cases of mUPD14, suggesting imprinting
      of a region(s) of chromosome 14 and defining a possible mUPD14 Syndrome.

PMID- 8872028
TI  - Is genomic imprinting involved in the pathogenesis of pseudotriploid
      neuroblastoma?

PMID- 8872029
TI  - Why is there no diploid overdose effect in Prader-Willi syndrome due to
      uniparental disomy?
AB  - Due to DNA technology, it is now apparent that the mechanisms of genetic disease
      are more complex than the model of a gene with biallelic expression in the
      diploid state. If a gene is imprinted, monoallelic expression is the norm when
      the chromosomes of a pair are inherited normally from each parent. Uniparental
      disomy (UPD) is the abnormal situation where both chromosomes of a pair come from
      the same parent. When the chromosome contains an imprinted gene, UPD may result
      in nullisomy or disomy for a functional copy of that gene. If there are two
      imprinted loci on the same chromosome, UPD for that chromosome results in
      nullisomy for one imprinted gene but functional disomy for the other a "diploid
      overdose" (DO). This situation has been well demonstrated in the Prader-Willi
      syndrome (PWS) which is the nullisomic phenotype for the PWS gene(s) on
      chromosome 15q11-13. Chromosome 15q11-13 also contains the gene for Angelman
      syndrome (AS) which has a phenotype distinct from PWS. Both loci are subject to
      imprinting--in PWS, the imprint is on the maternal chromosome 15, in AS it is on
      the paternal chromosome 15. All individuals with PWS due to maternal UPD, while
      functionally nullisomic for the PWS locus, are functionally disomic for the AS
      locus--a DO situation. Assuming that biallelic expression of an imprinted gene is
      harmful, one would expect DO for an imprinted gene to produce a phenotypic
      effect. Cases of PWS due to UPD do not appear to differ from those due to
      deletion (hypopigmentation in deletional cases can be explained by loss of D15S12
      downstream from the critical region). There is no good evidence of DO for the AS
      locus in PWS due to UPD. Why then was it 'necessary' in evolutionary terms to
      imprint the AS locus and maintain the imprint faithfully for life. A similar
      situation of two imprinted genes on the same chromosome occurs with IGF2 and H19
      on chromosome 11p15. Maternal imprinting for IGF2 and paternal imprinting for H19
      is the norm. Paternal UPD in this situation does lead to a DO effect, namely
      Beckwith-Wiedemann syndrome. The possibility of a DO effect needs to be
      considered when assessing the phenotypic spectrum of UPD for other chromosomes
      currently under investigation.

PMID- 8872030
TI  - The IPW gene is imprinted and is not expressed in the Prader-Willi syndrome.

PMID- 8872031
TI  - The mouse Xist gene: a model for studying the gametic imprinting phenomenon.

PMID- 8872032
TI  - Asynchronous replication patterns of imprinted genes in triploid cells.

PMID- 8872033
TI  - Isochromosome 15q of maternal origin in a Prader-Willi patient with pituitary
      adenoma.
AB  - We report on a Prader-Willi syndrome (PWS) patient carrier of a balanced 15q15q
      translocation and affected by a prolactin-secreting pituitary adenoma. Evidence
      provided by molecular studies indicates that the structural rearrangement is an
      isochromosome of maternal origin. According to the identification of isodisomy as
      the basis of the association of rare disorders and the recent report on
      chromosome 15 monosomy and nullisomy in pituitary adenoma, we suggest that in our
      case PWS and pituitary adenoma might be related.

PMID- 8872034
TI  - Molecular analysis of an extra inv dup(15)(q13) chromosome in two patients with
      Angelman syndrome.

PMID- 8872036
TI  - Phenotype-karyotype-genotype correlations in Prader-Willi and Angelman syndromes:
      preliminary results.

PMID- 8872035
TI  - Preferential loss of heterozygosity of chromosome 7 loci in simian virus 40 t/T
      antigen-induced mouse hepatocellular carcinomas does not involve H-ras mutations.

PMID- 8872037
TI  - Are ABL and BCR imprinted?

PMID- 8872038
TI  - Is genomic imprinting involved in the pathogenesis of hyperdiploid and haploid
      acute lymphoblastic leukemia of childhood?

PMID- 8872039
TI  - Influence of mouse-strain-specific factors on position-dependent transgene DNA
      methylation patterns.

PMID- 8872040
TI  - A new case of Beckwith-Wiedemann syndrome with an 11p15 duplication of paternal
      origin [46,XY,-21,+der(21), t(11;21)(p15.2;q22.3)pat].
AB  - We present a new case of 11p15 duplication (trisomy 11p15) in a boy (46,XY,
      21,+der(21), t(11;21)(p15.2;q22.3)] suffering from Beckwith-Wiedemann syndrome
      (BWS), whose phenotypically normal father carries a balanced translocation
      between chromosomes 11 and 21[46,XY, t(11;21)(p15.2;q22.3)]. The paternal
      grandmother has the same balanced translocation and is also clinically normal.
      BWS was suspected when the boy was 6 months old because of gigantism,
      macroglossia, visceromegaly, ear lobe creases and abdominal distention. Apart
      from the characteristic BWS phenotype, the boy has other features which are
      almost exclusively observed in 11p trisomy (high forehead with frontal upsweep of
      hair, wide central nose bridge, slightly beaked nose, chubby cheeks and severe
      mental retardation). So far, at least eight cases of 11p15 duplication have been
      described as patients with BWS. In six of these, the duplication was due to
      inheritance of a translocated or rearranged paternal chromosome. This was also
      the case in our patient. In the two other previously published cases, the 11p15
      duplications were de novo, but in one of these, DNA analysis has subsequently
      shown that the duplication was of paternal origin. We discuss our observations in
      relation to the above-mentioned previous cases of 11p15 duplication and the
      possible role of genomic imprinting in the etiology of BWS.

PMID- 8872041
TI  - Parental source effect on inherited mutations in the dystrophin gene of mice and
      humans.

PMID- 8872042
TI  - A case of Angelman syndrome arising as a result of a de novo Robertsonian
      translocation.
AB  - A male child has been identified with Angelman syndrome. He has been shown to
      carry a de novo Robertsonian 15/15 translocation where both chromosome 15s have
      been derived from the father. Consequently the disease in this instance is due to
      paternal uniparental disomy.

PMID- 8872044
TI  - No evidence for genomic imprinting in liver-born Down syndrome patients.
AB  - Despite numerous studies, the clinical heterogeneity of Down syndrome has no
      explanation. We have attempted to investigate the role of genomic imprinting in
      the phenotype of liveborn Down syndrome patients. Hundred fifty eight patients
      were investigated for parental origin of the extra chromosome 21 with standard
      cytogenetic analyses and with DNA plymorphic markers. The extra chromosome 21 was
      of paternal origin in 8 cases and of maternal origin in 150 cases. The phenotype
      of Down syndrome patients in whom the nondisjunction was of maternal origin, was
      not different from the phenotype of Down syndrome patients in whom the
      nondisjunction was of paternal origin. We conclude that imprinting may probably
      not play a role in the heterogeneity of Down syndrome phenotype.

PMID- 8872045
TI  - Molecular and clinical studies of Polish patients with Prader-Willi syndrome.
AB  - A group of 30 patients clinically described as having the Prader-Willi Syndrome
      (PWS) were studied using microsatellites from 15q11-13 and methylation analysis
      with probe PW71B (D15S63). The patients were categorized according to clinical
      symptoms. 80% of all patients were informative using molecular and cytogenetic
      methods. Among 8 patients with an atypical PWS phenotype, 2 showed uniparental
      disomy, and 2 had a mosaic deletion for 15q. The last 4 atypical and 2 typical
      patients had neither molecular defects confirmed by microsatellite analysis nor a
      parent-of-origin-specific methylation pattern for PWS. Our results confirm that
      methylation pattern analysis provides an additional and alternative
      microsatellite analysis to diagnose PWS.

PMID- 8872046
TI  - Absence of genomic imprinting at the DiGeorge locus.

PMID- 8872048
TI  - Analysis of triplet repeats of the FRAXA locus using a novel sequencing
      procedure.

PMID- 8872049
TI  - Immunohistochemical analysis of c-Fos and c-Jun in retinoblastoma.
AB  - The c-fos promoter is negatively regulated by the retinoblastoma (Rb)
      susceptibility-gene-encoded protein as well as by other genes involved in the
      control of transcription, cell cycle regulation and neoplastic transformation. We
      have examined by immunohistochemistry the c-Fos and c-Jun proteins in five cases
      of retinoblastoma in order to evaluate eventual alterations in their expression
      in vivo, possibly related to a gene mutation or to loss of Rb negative control.

PMID- 8872051
TI  - FRAXA and FRAXE: new tools for the diagnosis of mental retardation.

PMID- 8872054
TI  - Diagnosis and prevention of fragile-X syndrome. From the family study to the
      population screening programme: eighteen years of activity.

PMID- 8872055
TI  - RET receptor tyrosine kinase gene mutations: molecular biological, physiological
      and clinical aspects.

PMID- 8872056
TI  - Antihypertensive drugs and cerebral circulation.

PMID- 8872057
TI  - Lipoprotein lipase gene mutations D9N and N291S in four pedigrees with familial
      combined hyperlipidaemia.
AB  - The role of the lipoprotein lipase (LPL) gene in familial combined
      hyperlipidaemia (FCH) is unclear at present. We screened a group of 28 probands
      with familial combined hyperlipidaemia and a group of 91 population controls for
      two LPL gene mutations, D9N and N291S. LPL-D9N was found in two probands and one
      normolipidaemic population control. LPL-N291S was found in four probands and four
      population controls. Subsequently, two pedigrees from probands with the D9N
      mutation and two pedigrees from probands with the N291S mutation were studied,
      representing a total of 24 subjects. Both LPL gene mutations were associated with
      a significant effect on plasma lipids and apolipoproteins. Presence of the D9N
      mutation (n = 7) was associated with hypertriglyceridaemia [2.69 +/- 1.43 (SD)
      mmol L-1] and reduced plasma high-density lipoprotein cholesterol (HDL-C)
      concentrations (0.92 +/- 0.21 mmol L-1) compared with 11 non-carriers
      (triglyceride 1.75 +/- 0.64 mmol L-1; HDL-C 1.23 +/- 0.30 mmol L-1, P = 0.03 and
      P = 0.025 respectively). LPL-D9N carriers had higher diastolic blood pressures
      than non-carriers. LPL-N291S carriers (n = 6) showed significantly higher (26%)
      apo B plasma concentrations (174 +/- 26 mg dL-1) than non-carriers (138 +/- 26 mg
      dL-1; P = 0.023), with normal post-heparin plasma LPL activities. Linkage
      analysis revealed no significant relationship between the D9N or N291S LPL gene
      mutations and the FCH phenotype (hypertriglyceridaemia, hypercholesterolaemia or
      increased apo B concentrations). It is concluded that the LPL gene did not
      represent the major single gene causing familial combined hyperlipidaemia in the
      four pedigrees studied, but that the LPL-D9N and LPL-N291S mutations had
      significant additional effects on lipid and apolipoprotein phenotype.

PMID- 8872058
TI  - Islet cell autoimmunity and progression to insulin-dependent diabetes mellitus in
      genetically high- and low-risk siblings of diabetic children. The Childhood
      Diabetes in Finland (DiMe) Study Group.
AB  - Insulin-dependent diabetes mellitus (IDDM) risk was evaluated in 765 siblings
      based on prospective observation of islet cell antibodies (ICAs) and insulin
      autoantibodies (IAAs) as a function of the degree of HLA identity to the proband
      and HLA-DR alleles. Twenty-eight (3.7%) siblings progressed to IDDM over a median
      observation period of 5.8 years. ICAs had higher sensitivity than IAAS (100% vs.
      33% , P < 0.001), whereas persistent ICA positivity and double ICA/IAA positivity
      defined the highest actuarial risk (47% and 70%). Diabetes manifested after a
      mean of 3.2 years from the detection of ICAs in those siblings who were initially
      ICA negative and, importantly, the risk was equal to that of the siblings
      constantly positive from the first sample obtained. Although the combination of
      HLA identity and ICAs at or above 80 Juvenile Diabetes Foundation units carried
      the highest positive predictive value (77%), the high-risk HLA markers were
      insufficient to predispose siblings with low ICA levels to IDDM and low-risk HLA
      markers did not provide complete protection against high ICA levels and from
      subsequent IDDM. These results emphasize ICAs as the primary tool for risk
      evaluation in siblings followed by restricted HLA subtyping to reduce the
      population to be subjected to clinical intervention trials.

PMID- 8872059
TI  - Insulin resistance shows selective metabolic and hormonal targets in the elderly.
AB  - There has been no simultaneous evaluation of different aspects of insulin action
      in ageing. We studied 12 elderly (77 +/- 2 years) and 12 young (26 +/- 1 years)
      subjects with normal glucose tolerance and matched for sex, body mass index, lean
      body mass (LBM), blood pressure and physical activity, using a euglycaemic
      hyperinsulinaemic clamp at about 350 pmol L-1 in combination with [3H]-glucose
      infusion. In the elderly group, hepatic glucose production was normal, fasting
      serum insulin and C-peptide were significantly increased (P = 0.001) and glucose
      utilization (34.4 +/- 2.4 vs. 44.4 +/- 3.2 mumol kg-1 LBM min-1, P = 0.02) and
      the percentage maximal suppression of C-peptide (58 +/- 6% vs. 79 +/- 5%, P =
      0.02) during the clamp were reduced. Fasting plasma free fatty acid (FFA) and
      glycerol levels were similar in the two groups, but their percentage maximal
      suppression during the clamp was reduced in the elderly group (FFA 45 +/- 5% vs.
      77 +/- 6%, P = 0.001; glycerol 43 +/- 5% vs. 76 +/- 3%, P = 0.001). Branched
      chain amino acids (valine, leucine, isoleucine) and glucagon levels were similar
      in the two groups, both while fasting and during the clamp. Thus, insulin
      resistance in ageing appears selective on glucose utilization, inhibition of
      lipolysis and feedback inhibition of the B-cell secretion.

PMID- 8872060
TI  - Effects of glyceryl trinitrate on the pyloric motor response to intraduodenal
      triglyceride infusion in humans.
AB  - The retardation of gastric emptying induced by infusion of triglyceride into the
      small intestine is associated with suppression of antral pressure waves and
      stimulation of basal pyloric tone in combination with phasic pressure waves
      localized to the pylorus. The role of nitric oxide (NO) mechanisms in the control
      of pyloric motility was evaluated in 12 healthy male subjects (21-43 years),
      using the NO donor glyceryl trinitrate (GTN). Antropyloric pressures were
      measured with a manometric assembly incorporating nine sideholes, spanning the
      antrum and proximal duodenum, and a pyloric sleeve sensor. On separate days, an
      intraduodenal triglyceride infusion (10% intralipid at 1 mL min-1) was started
      during antral phase I activity and continued for 60 min. On one of the days GTN
      (600 micrograms) was given sublingually 20 min after start of the triglyceride
      infusion. The tonic pyloric motor response to triglyceride [5.6 (SEM 0.8,) vs.
      2.7 (1.3) mmHg, P < 0.001] and both the number 3.2 (0.2) vs. 2.2 (0.2) min-1, P <
      0.05] and amplitude [40 (4) vs. 27 (5) mmHg, P < 0.05] of phasic isolated pyloric
      pressure waves were reduced by GTN. These observations suggest that NO mechanisms
      are involved in the regulation of pyloric motor activity in humans.

PMID- 8872061
TI  - Peripancreatic lymphoadenopathy and extrahepatic immunological manifestations in
      chronic hepatitis C.
AB  - The aim of the study was to determine the role of peripancreatic lymph node
      swelling in systemic immunological alterations during chronic hepatitis C (HC).
      The prospective study was carried out as a clinical study in a university
      hospital. Clinical, haematochemical and ultrasonographic findings in 182 patients
      were studied. Ultrasonography was performed by the same operator and the findings
      were evaluated blind without the operator knowing the clinical and
      haematochemical parameters. Hepatitis B virus (HBV) markers, anti-HCV antibodies,
      LKM1, cryoglobulinaemia, rheumatoid factor and anti-tissue antibodies were
      determined. Liver biopsy was carried out in 43 of the 182 patients. One or two
      pathological peripancreatic lymph nodes (PLNs) were present in 30 of the 182
      patients and, of the 30, 28 were anti-HC positive. Only one patient in the non
      PLN group was positive for anti-HCV, there being statistical significance (P <
      0.0001) between the PLN and non-PLN groups. In HCV-positive patients,
      extrahepatic immunological manifestations were observed (cryoglobulinaemia;
      positivity to anti-smooth muscle, antinuclear and antimitochondrial antibodies;
      positivity to rheumatoid factor and LKM1). In five patients the presence of focal
      lymphocytic aggregates was detected by biopsy, whereas one patient presented
      typical ocular lesion of Mikulicz's syndrome. Our results may confirm the marked
      lymphotropism shown by the HC virus and indicate more complex immune system
      involvement, especially in view of the coexisting signs of immune system
      involvement related to the presence of intrahepatic cellular aggregates detected
      in our study. We believe that the peripancreatic adenopathy in chronic HCV
      hepatitis is an important diagnostic sign and may indicate an involvement of the
      C virus in the still unexplained extrahepatic immunological disorders.

PMID- 8872062
TI  - Decrease in lipoprotein(a) after renal transplantation is related to the
      glucocorticoid dose.
AB  - Serum lipoprotein(a) [Lp(a)] concentrations and apolipoprotein(a) phenotypes were
      determined in 46 patients with end-stage renal disease both before as well as 1
      week and 1, 3 and 6 months after renal transplantation. Immunosuppressive therapy
      consisted of cyclosporin A, prednisone and azathioprine. Before transplantation
      median Lp(a) levels did not differ between the patients and a healthy control
      group. A highly significant decrease (P < 0.001) in Lp(a) levels was observed in
      both male and female patients 1 week after transplantation. This marked reduction
      in Lp(a) occurred at a time when patients were receiving the highest doses of
      corticosteroids. As steroid doses were gradually tapered, Lp(a) concentrations
      subsequently increased, although at 6 months levels were still significantly
      reduced (P < 0.01) in women. No significant correlation was observed between
      Lp(a) and whole-blood cyclosporin levels, nor was there any correlation with the
      azathioprine dose. The reduction in Lp(a) concentrations was seen for all apo(a)
      phenotypes observed in the study.

PMID- 8872063
TI  - Divergent effects of propranolol and nadolol in isolated mesenteric arteries from
      normal and portal hypertensive rats.
AB  - Propranolol, a non-selective beta-blocker, is used for treatment of portal
      hypertension as it is believed to diminish splanchnic blood flow both by reducing
      cardiac output (beta(1)-blockade) and by increasing splanchnic arteriolar
      resistance (beta(2)-blockade). However, possible vasodilatory properties of
      propranolol at higher concentrations may counteract splanchnic vasoconstriction.
      Nadolol, another nonselective beta-blocker, has also been suggested for treatment
      of portal hypertension. The aim of the present study was to investigate the
      effects of various concentrations of propranolol and nadolol on vascular
      resistance in isolated perfused mesenteric arterial beds from normal and portal
      hypertensive rats. At concentrations of 10(-7) mol L-1 to 10(-6) mol L-1 neither
      propranolol nor nadolol changed pressor responses to noradrenaline in normal
      rats. However, nadolol 10(-5) mol L-1 significantly increased, whereas
      propranolol 10(-5) mol L-1 reduced, noradrenaline-induced vasoconstriction both
      in normal and in portal hypertensive rats. This unexpected vasodilatory effect of
      propranolol at high concentrations was present in preparations stimulated by both
      noradrenaline and methoxamine but not vasopressin and thus may be due to
      competitive alpha-receptor blockade. In contrast, nadolol lacked this effect and
      produced splanchnic arteriolar vasoconstriction at high concentrations also.

PMID- 8872064
TI  - New evidence that serum beta(2)-microglobulin behaves as a biological marker of
      bone remodelling in women.
AB  - Having observed that serum beta(2)-microglobulin concentration correlates with
      serum tartrate-resistant acid phosphatase (TRAP) concentration in postmenopausal
      osteoporosis, and that metacarpal endosteal diameter is dependent on bone
      resorption, we correlated the two biochemical parameters with the radiographic
      parameter to determine if beta(2)-microglobulin behaves like a biological marker
      of bone remodelling. In 105 women (mean age 68 +/- 4 years) consisting of 60
      normal postmenopausal women and 55 osteoporotic postmenopausal women, there was a
      significant positive correlation between metacarpal endosteal diameter and these
      two biochemical values (r = 0.66 with beta(2)-microglobulin and r = 0.68 with
      TRAP in the osteoporotic postmenopausal women; r = 0.48 with beta(2)
      microglobulin and r = 0.56 with TRAP in the normal postmenopausal women; P <
      0.001 for all comparisons). All three measurements were significantly higher (P <
      0.001) in the osteoporotic postmenopausal women than in the normal postmenopausal
      women. These findings show that serum beta(2)-microglobulin behaves like a
      biological marker of remodelling.

PMID- 8872065
TI  - Longitudinal analysis of soluble intercellular adhesion molecule 1 in retinal
      vasculitis patients.
AB  - Increased levels of soluble intercellular adhesion molecule 1 (sICAM-1) in serum
      have been demonstrated in several human disease conditions. We have previously
      shown, in a point-prevalence study, a positive correlation between sICAM-1 levels
      and disease relapse in patients with idiopathic retinal vasculitis. We now report
      a longitudinal study over 1 year in which sICAM-1 levels were compared with
      clinical disease status in order to determine this relationship further. Serum
      samples from 11 patients with idiopathic retinal vasculitis were tested for the
      presence of sICAM-1 by enzyme linked immunosorbent assay. Eight control subjects
      were also tested. Five out of 11 patients presented with relapse and had raised
      sICAM-1 levels compared with quiescent periods of their disease. Five out of 11
      patients showed no relapse over 1 year and also no increase in sICAM-1 levels.
      One patient showed increased levels of sICAM-1, but no clinical signs of relapse.
      These results indicate that sICAM-1 is associated with disease activity in
      retinal vasculitis patients and could indicate dysfunction of the blood-retina
      barrier.

PMID- 8872066
TI  - Elevation of plasminogen activator inhibitor 1 in borderline hypertension is
      linked to concomitant metabolic disturbances.
AB  - In the present study we investigated plasma levels of plasminogen activator
      inhibitor 1 (PAI-1), fibrinogen and von Willebrand factor (vWF) in borderline
      hypertensive (BHT) men [diastolic blood pressure (DBP) 85-94 mmHg, n = 75] and
      age-matched normotensive (NT) control subjects (DBP < or = 80 mmHg, n = 75), in
      relation to smoking, body mass index (BMI) and fasting lipoprotein and insulin
      levels. PAI-1 levels were elevated in the BHT group [16.3 vs. 13.7 arbitrary
      units (AU), P = 0.032], whereas levels of fibrinogen and vWF were similar in the
      two groups. The PAI-1 elevation was even more pronounced in dyslipidaemic BHT
      subjects than in normolipidaemic NT subjects (20.0 vs. 10.3 arbitrary units (AU),
      P = 0.001). PAI-1 levels showed strong correlations with insulin, lipoproteins
      and BMI (P < 0.01-0.001), but not with DBP. The results show that disturbances in
      the fibrinolytic system appear even in borderline hypertension. The elevation of
      PAI-1 levels seems to be more strongly linked to concomitant metabolic
      disturbances than to blood pressure levels.

PMID- 8872067
TI  - Effects of the sulphydryl donor N-acetyl-L-cysteine on nerve conduction,
      perfusion, maturation and regeneration following freeze damage in diabetic rats.
AB  - Peripheral nerve conduction velocity deficits in diabetic rats depend on
      decreased nerve perfusion, which may be related to increased free radical
      activity and impaired endogenous protection by the glutathione redox cycle. We
      studied the effect of treatment with the glutathione precursor N-acetyl-L
      cysteine on nerve conduction, blood flow, maturation and regeneration. Two months
      of diabetes in mature rats caused 20% and 48% deficits in sciatic motor
      conduction velocity and endoneurial blood flow, respectively, which were largely
      corrected by N-acetyl-L-cysteine treatment during the second month. In young
      nondiabetic rats, sciatic motor conduction velocity increased by 31% over 6
      weeks. Diabetes halved the conduction velocity maturation rate, however N-acetyl
      L-cysteine treatment allowed a normal pattern of development. After 1 month of
      treated or untreated diabetes, the sciatic nerve was lesioned by a liquid
      nitrogen-cooled probe. Myelinated fibre regeneration distance, determined
      electrophysiologically, was reduced by 12.2% with diabetes; this was prevented by
      N-acetyl-L-cysteine treatment. Thus, the data stress the importance of free
      radical-mediated changes in the aetiology of experimental diabetic neuropathy.

PMID- 8872068
TI  - Involvement of the L-arginine-nitric oxide pathway in hyperglycaemia-induced
      coronary artery dysfunction of isolated guinea pig hearts.
AB  - The effects of hyperglycaemia and L-arginine on flow-induced reduction of
      coronary artery resistance were investigated in isolated guinea pig hearts. In
      the presence of indomethacin, hyperglycaemia caused an increase in flow-induced
      vasodilatation (P < 0.05). Hyperosmotic controls failed to mimic this effect.
      Addition of L-arginine strongly enhanced this effect. Addition of D-arginine
      failed to mimic the effects of L-arginine. The effect of L-arginine was abolished
      by co-administration of NG-nitro-L-arginine. In the absence of indomethacin and L
      arginine, the effect of hyperglycaemia was blunted, suggesting the formation of
      vasoconstrictive prostanoids. Addition of L-arginine again resulted in a
      significant increase in flow-induced vasodilatation. In conclusion our results
      suggest that increased flow-induced vasodilatation under hyperglycaemic
      conditions depends on an adequate supply of L-arginine to maintain sufficient
      formation of nitric oxide.

PMID- 8872069
TI  - Pulmonary eosinophilia.
AB  - The pulmonary eosinophilias are a diverse group of disorders characterised by
      pulmonary infiltrates, rich in eosinophils usually associated with a peripheral
      blood eosinophilia. Known causes of pulmonary eosinophilia include fungi--in
      particular Aspergillus fumigatus, parasites, toxins and drugs. Pulmonary
      eosinophilias of unknown cause include Loffler's syndrome, acute and chronic
      eosinophilic pneumonia, the hypereosinophilic syndrome, bronchocentric
      granulomatosis and pulmonary eosinophilia associated with vasculitis. The chest
      radiographic appearances of pulmonary eosinophilia are often characteristic and
      HRCT in selected cases can give important additional information.

PMID- 8872070
TI  - Lobar collapse: basic concepts.
AB  - Lobar collapse is important to diagnose when present, as it may indicate the
      presence of a central bronchial obstructing lesion. In some instances, its
      appearance is rather classical and easily diagnosed. In other instances, its
      appearance can challenge even the most experienced radiologist. In yet other
      instances, it may be simulated by other disease processes. This material
      represents a discussion of some basic concepts and signs the author considers
      important in determining whether or not lobar collapse is present.

PMID- 8872071
TI  - Chest trauma.
AB  - Trauma is a major cause of morbidity and mortality worldwide. Despite the advent
      of specialised trauma centres the outcome of patients who sustain major trauma
      remains disappointing. Plain radiography and more advanced imaging techniques
      such as ultrasound, computerised tomography (CT) and angiography, have a major
      role to play in the early decision making and subsequent management of patients
      who sustain polytrauma. This article discusses the choice of emergency imaging
      techniques available in chest trauma for clinicians and radiologists; their
      evaluation and some of the common pitfalls that may lead to errors of
      interpretation.

PMID- 8872072
TI  - Lung cancer staging: the role of computed tomography and magnetic resonance
      imaging.
AB  - Because complete resection remains the only reliable method of cure of lung
      cancer, one important aim of preoperative staging is to select patients with
      localised disease who may benefit from surgery, while avoiding unnecessary
      thoracotomies in patients with unresectable neoplasm. Computed tomography (CT) of
      the chest is a valuable method for staging local and regional spread of lung
      neoplasms, although limitations in its accuracy are well-known. While gross
      invasion of the mediastinum and major structures as well as the presence of
      metastatic disease can be easily demonstrated with CT, differentiation between
      tumour contiguity and subtle invasion of mediastinum or chest wall often remains
      a problem. Although magnetic resonance imaging (MRI) may have the same
      limitations as CT, in specific situations it may be superior in diagnosing
      minimal chest wall or mediastinal invasion. Moreover, MRI is useful in the
      assessment of patients with superior sulcus tumours as well as in patients with
      contraindication to intravenous administration of ionic contrast material. Since
      nodal size is the only useful criterion for evaluating lymph node metastases, CT
      and MRI show similar, poor accuracies in lymph node staging resulting from both
      low sensitivity (normal-sized nodes may contain microscopic metastases) and low
      specificity (enlarged lymph nodes may be reactive). For this reason, if enlarged
      lymph nodes are detected, further evaluation is recommended before excluding the
      patient from a potentially curative resection. Advantages and limitations of CT
      and MRI in the preoperative staging of non-small-cell carcinoma are reviewed in
      this article. The imaging of small-cell carcinoma is not included because most
      patients with this cell type do not benefit from surgical resection. Similarly we
      do not discuss imaging of distant metastases.

PMID- 8872073
TI  - Chest imaging in the intensive care unit.

PMID- 8872074
TI  - Interventional chest radiology.
AB  - The authors review the various interventional radiology techniques currently used
      in 1996 by a Medico-Radio-Surgical team. CT guided needle biopsy has an important
      place in the diagnostic approach to parenchymal as well as mediastinal tumours.
      But CT guidance allows also routine drainage of thoracic collections and
      sometimes thoracic sympatholysis. Superior vena cava and tracheobronchial
      stenting are palliative treatments as the percutaneous aspergilloma treatment.
      Embolization of bronchial and thoracic systemic arteries are also palliative but
      effective therapeutic procedures as well as vasoocclusion for arterio-venous
      fistulae.

PMID- 8872075
TI  - Application of whole-mount section of lung specimen in study of radiologic
      pathologic correlations.
AB  - We evaluated the usefulness of the whole-mount section of the inflated-fixed lung
      specimen in the study of radiologic-pathologic correlations. Altogether, 24
      resected fresh lobe specimens with 1.5- to 3.0-cm solitary pulmonary carcinomas
      or tuberculomas were inflated with air, intrabronchially fixed by infusing
      Heitzman's solution, and finally cut into 10- to 15-micron-thick whole-mount
      sections for the histopathological examination. All 24 inflated-fixed lobes were
      satisfactorily soft as sponge, sufficiently springy, and kept their original
      shape. All whole-mount sections clearly presented the complete morphological
      features of the whole lobes, and could be directly observed by the naked eye and
      examined under microscopy. The use of the whole-mount section of the lung
      specimen may facilitate precisely and effectively the studies of the radiologic
      pathologic correlations.

PMID- 8872076
TI  - Recurring tracheal leiomyoma presenting as a calcified mediastinal mass.

PMID- 8872077
TI  - MR imaging of pulmonary hydatid disease.

PMID- 8872078
TI  - Pseudo-pneumoretroperitoneum secondary to lumbar emphysema: CT demonstration in
      two cases.
AB  - Several conditions may simulate the radiolucent appearances of
      pneumoretroperitoneum at plain film. These include gas shadows in locations other
      than the retroperitoneal space or fluid within the retroperitoneal compartments.
      Two cases of emphysema within the soft tissues of the back mimicking
      pneumoretroperitoneum on plain radiographs are described. One case was secondary
      to epidural anesthesia and another to trauma. In both, computed tomography (CT)
      led to the correct diagnosis. The possible pitfalls in the differential diagnosis
      of retroperitoneal gas are described with emphasis of the diagnostic role of CT.

PMID- 8872079
TI  - Aging and cognition: methodological differences in outcome.
AB  - A series of longitudinal and cross sectional studies, collected as part of the
      Seattle Study, were reanalyzed. A longitudinal sequential analysis (N = 232),
      wherein subjects were measured every seven years for four time periods, was
      completed on the Primary Mental Abilities test. Cohort differences were at least
      as strong as age differences; cohorts were generally relatively stable over the
      measured periods, showing little cognitive decline. A cross-sectional sequential
      analysis (N = 2813) was completed for the same time periods; decline with age was
      more evident than with the longitudinal sequential analysis. A cross-sectional
      analysis for the fourth time period (N = 611) showed the most marked decline of
      all. Interpretation of outcome was highly dependent on the analysis used.

PMID- 8872080
TI  - Measuring human functional age: a review of empirical findings.
AB  - A review of empirical functional age studies published in English was conducted.
      Types of biomarkers used in functional age studies included sensorimotor,
      cognitive, psychosocial, behavioral, anthropometric, biomedical, physiological,
      and dental variables. Previous criticisms of the validity and utility of
      functional age research were evaluated with reference to empirical studies. While
      some of these criticisms remain valid, areas of research currently using
      established biomarkers to predict functional outcomes were identified, including
      driving, falls, and cognitive functioning. It was concluded that the success of
      functional age research is dependent on the relevance of biomarkers to specific
      functional outcomes.

PMID- 8872081
TI  - Adult age differences in the effects of environmental context on memory
      performance.
AB  - In two experiments, we examined the hypotheses that the memory performance of
      older adults is more dependent than that of younger adults on environmental
      context, and that the integration of to-be-remembered items with contextual cues
      benefits older more than younger adults. When younger and older adults were shown
      simple line drawings that were not explicitly associated with the external
      environment, there was no effect on recall of a change in environmental context
      for either age group. However, when subjects heard sentences that connected the
      simple drawings with environmental cues, an environmental context effect was
      observed. Both age groups recalled more in the same than in a different
      environment, and the magnitude of the facilitation effect of the familiar context
      was equal for younger and older adults. However, the integration of the to-be
      remembered items with the context facilitated recall regardless of the context
      present at retrieval, and this effect was larger for younger adults, suggesting
      that the younger adults were better able to use the provided integrations than
      were the older adults.

PMID- 8872082
TI  - Memory enhancement program for community-based older adults: development and
      evaluation.
AB  - The purpose of the study was to develop a multifactorial memory enhancement
      program for community-dwelling older adults aimed at encouraging positive beliefs
      and behaviors about memory function and abilities in later life. The study
      evaluated the effectiveness of cognitive restructuring techniques (56 subjects)
      as compared to traditional memory training techniques (61 subjects) for purposes
      of enhancing memory performance. Posttest assessments were conducted after 10
      weeks of memory training. Follow-up assessments were conducted 9 weeks later to
      assess maintenance of memory performance and memory beliefs. Three 2 x 3
      (Treatment x Time) repeated measures multivariate analyses of variance were
      conducted to evaluate the effects of two types of intervention on memory
      performance, memory perception, and affective symptomatology over time. Results
      suggest that cognitive restructuring techniques may help community-dwelling older
      adults gain control over their beliefs about memory and thereby enhance their
      memory performance.

PMID- 8872083
TI  - Using a memory handbook to improve everyday memory in community-dwelling older
      adults with memory complaints.
AB  - Community-dwelling, nondemented older people (60-70 years) with reported memory
      complaints were randomly assigned to either a memory-handbook (MHB) group (n =
      20) or a placebo group (n = 20). The MHB group members were given a self
      contained memory handbook and were individually trained on two of the handbook's
      sections that related to (a) remembering a person's name and (b) prospective
      memory, for approximately 30 minutes each. The placebo group was given an
      instructional pamphlet with a description of three list-learning mnemonics as a
      placebo treatment. Subjects were tested before and after the intervention. When
      compared with the placebo group, the MHB group members significantly improved
      their performance on a face-naming task and a strategies knowledge questionnaire,
      but not on the prospective memory measures, when compared with the placebo group.
      In addition, the MHB group showed a significant advantage on an everyday memory
      diary that was filled out by all subjects following the intervention. Following
      the study, the placebo group was also given the memory handbook, and both groups
      were then assessed on their knowledge and use of strategies by questionnaire at a
      4-month follow-up. At this time the MHB group appeared to maintain most of its
      original gains, while the placebo group made some improvement.

PMID- 8872084
TI  - Influence of intrinsic particle properties on the assessment of convective gas
      transport by aerosol bolus technique.
AB  - Aerosol bolus measurements are increasingly being used in patients and healthy
      subjects to assess convective gas transport and mixing in the lungs. To
      investigate the extent to which intrinsic particle properties confound parameters
      derived for the assessment of intrapulmonary transport, bolus inhalation
      experiments were performed in six anesthetized, intubated, and mechanically
      ventilated beagle dogs using DEHS particles of 0.5, 1, or 2 microns diameter.
      Therefore, particle displacement by diffusion varied by a factor of two, settling
      velocity by a factor of 13, and particle inertia as inferred from the stopping
      distance by a factor of 16. By using a standardized breathing maneuver 6-mL
      boluses were inhaled into lung depths between 75 and 475 mL. Mode, half-width,
      and intrapulmonary particle deposition along with mean, standard deviation, and
      skewness of the particle concentration distributions in the expired air were
      determined. For all particle sizes studied particle deposition increased with
      increasing lung depth not exceeding 25% for 0.5-micron particles, but being 80%
      in deep lung regions for 2-micron particles. Whereas half-width and standard
      deviation exhibited only small differences between particle sizes (less than
      20%), mode and mean of the exhaled bolus were clearly dependent on particle size,
      in particular for particles inhaled deep into the lung. No significant effects
      were detectable for the skewness. Hence, convective mixing assessed by half-width
      or standard deviation is only slightly dependent on particle size, but the
      estimate of convective bulk transport as inferred from the mean volume from which
      the bolus is exhaled is highly dependent on particle size. Yet, the intrinsic
      mobility of unit-density 0.5-micron particles was found to be small enough to
      consider these particles as ideal tracers for probing convective gas transport in
      the lungs.

PMID- 8872085
TI  - NK1 receptor antagonist CP-99,994 inhibits cigarette smoke-induced neutrophil and
      eosinophil adhesion in rat tracheal venules.
AB  - The involvement of neurokinin NK1 receptors in cigarette-induced adhesion of
      neutrophils and eosinophils to venules of the airway mucosa was investigated.
      Rats were pretreated with the NK1 receptor antagonist CP-99,994 (4 mg/kg IV), its
      vehicle, or its inactive enantiomer CP-100,263 before exposure to cigarette
      smoke. Adherent neutrophils and eosinophils were stained histochemically for
      endogenous peroxidase activity and were counted in tracheal whole mounts. Plasma
      leakage was quantified be stereological measurements of the extravasation of
      Monastral blue. Cigarette smoke induced the adhesion of 104 + 17 neutrophils and
      10.4 +/- 1.7 eosinophils per square millimeter of mucosa. CP-99,994 reduced
      neutrophil and eosinophil adhesion by 66 and 61%, respectively, and reduced
      plasma extravasation by 61% (p < .05), but CP-100,263 had no significant effect.
      The inhibitory effects of CP-99,994 appeared to be specific because CP-99,994 had
      no effect on neutrophil and eosinophil adhesion, or on plasma extravasation
      induced by platelet activating factor, an inflammatory stimulus acting
      independently of NK1 receptors. These results suggest that NK1 receptors are
      involved in cigarette smoke-induced adhesion of neutrophils and eosinophils to
      the endothelium of venules in the rat tracheal mucosa.

PMID- 8872086
TI  - Isolation of differentially expressed cDNAs during ferret tracheal development:
      application of differential display PCR.
AB  - The technique of differential display polymerase chain reaction (DD-PCR) was used
      to identify cDNA sequences, which are temporally expressed during ferret tracheal
      airway development. Such differentially expressed cDNAs may ultimately prove to
      be useful markers in elucidating mechanisms of epithelial differentiation and
      submucosal gland development in the airway. Using two sets of oligonucleotide
      primers 15 differentially amplified cDNAs were isolated by comparative reverse
      transcriptase (RT) PCR of 6-h and 3-day postnatal tracheal poly-A mRNA. In situ
      hybridization was used to assess the reliability of this method and confirm the
      differential mRNA expression patterns of cloned cDNAs. Results of in situ
      hybridization analysis demonstrated that 10 of the 15 cDNA sequences gave a
      temporally regulated pattern of expression, which was concordant with that of the
      differential display. Furthermore, sequence analysis of the 15 isolated cDNAs
      revealed that the majority of clones were amplified from two inverted decamer
      primers. These findings demonstrate the lack of poly-T priming in the
      differential display reaction, which suggests that this method may yield
      substantially more information regarding the coding sequence of cloned genes. In
      support of this observation, 6 of the 15 cDNA sequences contained one complete
      open reading frame. Although the majority of cDNAs demonstrated no homology to
      sequence data bases at the DNA or amino acid level, clone FT-4, which
      demonstrated a differential expression pattern limited to 3-day tracheal time
      points, was composed of a 10-amino acid repeat domain that was structurally
      similar to neuropeptide anthoRFamide and barley D hordein seed protein. A second
      interesting clone, FT-3, demonstrated an infrequent pattern of expression within
      a subset of epithelial cells limited to early developmental time points (6 h) and
      was dramatically reduced by 3 days postnatally. Several additional clones with no
      homologies to previously cloned genes demonstrated expression patterns that were
      also temporally regulated throughout tracheal development. Although the function
      of these temporally regulated genes has not been determined, these genes may
      ultimately prove to be useful markers of cellular differentiation during tracheal
      development.

PMID- 8872087
TI  - Antioxidants in bronchoalveolar lavage fluid cells isolated from ozone--exposed
      normal and ascorbate-deficient guinea pigs.
AB  - Previous studies have indicated that systemic deficiency in one of the critical
      antioxidants, ascorbate, does not significantly exacerbate ozone-induced lung
      injury and changes in lung antioxidants following longer-term exposure. Because
      alveolar cells encounter the highest ozone dose upon exposure and lack direct
      blood supply, systemic ascorbate deficiency may exacerbate ozone response on
      antioxidants within these cells. Female Hartley guinea pigs (30 days old) were
      fed either a regular guinea pig chow or chow that lacked ascorbate. The dietary
      regimen was started 1 week prior to exposure, continued through ozone exposure
      (0, 0.2, 0.4, or 0.8 ppm, 23 h/day, 1 week), and during 1 week recovery in clean
      air following exposure. Immediately after 1 week of exposure or recovery, lungs
      were lavaged and cells were counted in bronchoalveolar lavage fluid (BALF).
      Protein, ascorbate, uric acid, total glutathione (GSH), and alpha-tocopherol were
      analyzed in these cells. Ozone caused an increase in total BALF cells and total
      cellular protein after 0.4 and 0.8 ppm ozone. The increase was more pronounced in
      ascorbate-deficient guinea pigs. Protein per million cells, however, was not
      changed by ozone or diet. In ascorbate-sufficient guinea pigs, ascorbate levels
      were increased only after 0.2 ppm ozone. However, uric acid (at 0.4 and 0.8 ppm
      ozone) and GSH (at all concentrations of ozone) levels were increased in both
      dietary groups. Ascorbate deficiency did not affect basal uric acid or GSH levels
      in BALF cells. There was a small diet-related depletion in cellular alpha
      tocopherol. Ozone exposure also decreased alpha-tocopherol regardless of diet.
      The above changes except for alpha-tocopherol appeared to be reversed after 1
      week of recovery in both dietary groups. In summary, ozone is capable of inducing
      a mechanism that increases antioxidants such as ascorbate, GSH, and uric acid.
      GSH and uric acid are not affected by ascorbate deficiency, but alpha-tocopherol
      is depleted. GSH and uric acid may be critical in ozone-induced adaptation during
      ascorbate deficiency.

PMID- 8872088
TI  - Neutrophil activation and lung injury associated with chronic endotoxemia in
      rabbits.
AB  - Chronic endotoxemia produces emphysematous lung destruction in several animal
      models. The present study was designed to examine changes in the
      polymorphonuclear leukocytes (PMN) and the lung parenchyma of rabbits that
      received either saline (control, n = 6) or Escherichia coli endotoxin (LPS, n =
      6) 2-3 times weekly for 15 to 28 weeks. Peripheral blood was collected just
      before and after each intravenous injection and lung tissue was processed at the
      end of the experiment. PMN myeloperoxidase was stained with diaminobenzidine
      tetrahydrochloride (DAB)-H2O2, and CD11/CD18 was detected with immunogold. The
      changes in the PMN and the lung parenchyma were quantitatively analyzed. The
      results show that each dose of LPS produced an initial fall, followed by a rise
      in the circulating mature and immature PMN cell counts. Repeated doses of LPS
      induced PMN activation, degranulation, and an increase in the mean thickness of
      the alveolar wall (control, 4.1 +/- 0.2; LPS, 5.1 +/- 0.5; p < .05) at 28 weeks
      without evidence of alveolar septa destruction. Morphometric analysis of
      intravascular PMN showed an increase in the volume (V) of myeloperoxidase
      containing azurophil granules (control, 6.1 +/- 1.3 microns3; LPS, 13.1 +/- 2.8
      microns3; p < .05); a trend for a decrease in the V of specific granules
      (control, 15.8 +/- 3.4 microns3; LPS, 10.2 +/- 1.5 microns3; p = .09); an
      increase in the V of the cytoplasm (control, 37.3 +/- 6.4 microns3; LPS, 54.5 +/-
      7.1 microns3; p < .05); and an increase in CD11/CD18 expressed as the number of
      gold particles per micrometer of cell surface membrane (G/micron) (control, 7.1
      +/- 1.4 G/micron; LPS, 18.1 +/- 7.8 G/micron; p < .05). The results indicate that
      chronic endoxemia in rabbits, accelerates the release of PMN from the bone
      marrow, enhances the retention of both mature and immature activated PMN in the
      pulmonary microvessels, and causes alveolar wall thickening rather than
      emphysematous lung destruction.

PMID- 8872089
TI  - Characterization of radioiodinated lung surfactant protein A (SP-A) and the
      effects of oxidation on SP-A quaternary structure and activity.
AB  - Lung surfactant protein A (SP-A) is the most abundant surfactant-associated
      protein present in the lung and respiratory tract. SP-A binds to several
      pathogens via its C-type lectin domains, and may act as an opsonin, mediating
      adhesion to cells via the collectin receptor. Binding studies using SP-A are made
      difficult by its apparent instability following radioiodination. This study
      investigated the effect of oxidation (via radioiodination and exposure to H2O2)
      on the structural and functional characteristics of SP-A. Radioiodinated SP-A,
      stored at 4 degrees C, retained carbohydrate binding activity after labeling.
      After 10 days storage, the radioiodinated SP-A was indistinguishable on SDS-PAGE
      from freshly radioiodinated SP-A, but sedimentation coefficient and Stokes radius
      values changed dramatically, indicating SP-A depolymerization. Such a quaternary
      structural breakdown, with a concomitant reduction in carbohydrate binding
      activity, is likely to be due to oxidative cleavage of disulfide bonds.
      Comparable results were observed upon radioiodination of the structurally similar
      molecule C1q. Consequently, the effect of prolonged incubation with H2O2 upon SP
      A was investigated, with similar results. Thus, exposure to oxidizing agents
      leads to breakdown of the hexameric quaternary structure of SP-A, often to native
      polypeptides, with an attendant loss of binding activity. Such an effect may have
      consequences for the physiological role of SP-A in the lung.

PMID- 8872090
TI  - Racial differences in allelic distribution at the human pulmonary surfactant
      protein B gene locus (SP-B).
AB  - Variable numbers of composite repetitive motifs are found in different
      individuals within intron 4 of the surfactant protein B (SP-B) gene (Biochem J.
      1995;305:583). This study tests the hypothesis that the distribution of SP-B
      alleles differs among racial/ethnic groups. A total of 412 SP-B alleles were
      analyzed: 206 from Caucasian, 68 from African-American, and 138 from Nigerian
      individuals. Twelve groups of alleles (A-L) carrying 3 to 18 motifs were found.
      The distribution of the 12 alleles in the Caucasian group differs from that found
      in the Nigerian (p < .001) and African-American (p < .001) populations. The
      overall distribution of alleles between the African-American and the Nigerian
      populations were not statistically different. Specific alleles were also present
      in different proportions among the groups studied. For example, the most common
      allele (allele E) in all three populations is present at a significantly higher
      frequency in Caucasians than in the other two populations, but its frequency does
      not differ from the Nigerian and African-American groups. A less frequent allele,
      H, also differs significantly when Caucasians are compared with each of the other
      two populations, but the frequency of this allele is comparable between the
      African-American and Nigerian populations. To assess the importance of having
      comparable racial composition between the control and the case groups, a group of
      African-Americans with respiratory distress syndrome (RDS) (n = 40) was compared
      with the African American and the Caucasian groups studied above. No significant
      difference was observed between the racially matched groups but a significant
      difference (p = .006) was observed between the racially mixed groups. The results
      indicate that the distribution of SP-B alleles differs between the racial groups
      but not between the ethnic groups studied. Thus, racial composition of the groups
      under study is important when considering whether particular alleles at this
      locus predispose to inherited disorders.

PMID- 8872093
TI  - The journey of incontinent women from community to university clinic;
      implications for selection bias, gatekeeper function, and primary care.
AB  - BACKGROUND: The selection process of patients from community to hospitals may
      introduce bias into research and hamper the generalization of hospital-based
      research back to general practice. OBJECTIVE: The objective of this study was to
      use female urinary incontinence as a model in an attempt to provide empirical
      support for selection bias. METHOD: The analyses are based on three populations
      of incontinent women: community level (epidemiological survey, 535 women),
      primary care level (general practice, prospective clinical study, 105 women), and
      secondary care level (university hospital, prospective clinical study, 228
      women). RESULTS: The general practice patients were older and the hospital
      patients younger than those in the community. From community via general practice
      to hospital, there was an increase in duration, frequency of leakage, amount of
      leakage, severity and perceived impact of incontinence. Help-seeking at the
      primary care level was associated with increasing age and severity, and with urge
      symptoms and substantial impact. Referral from general practice to hospital level
      was only associated with age and urge symptoms. CONCLUSION: The study provides
      empirical evidence to support the existence of selection bias. This phenomenon
      must not be overlooked when recommendations developed at the consultant level are
      presented at a level with a significantly different clinical picture of a
      condition.

PMID- 8872092
TI  - Prevention in practice: results of a 2-year follow-up of routine health promotion
      interventions in general practice.
AB  - BACKGROUND: The effectiveness of health promotion activity in general practice on
      risk factor reduction for coronary heart disease remains the subject of active
      debate. OBJECTIVE: The study aimed to assess the impact of practice-based health
      check-ups on health behaviours over a 2-year period. METHOD: A general practice
      cohort of 7123 patients from 18 practices was surveyed. Eight hundred and forty
      (12%) patients had been offered a health check within a 12-month period from
      September 1992 and 621 (9%) received one. Two hundred and fifty patients (40%)
      were asked back for follow-up after their health check. RESULTS: Over a 2-year
      period there was no difference in smoking cessation, alcohol consumption, weight
      loss nor the amount of exercise taken between those who attended for a health
      check and those who did not. The food score chosen to assess dietary change
      (Oxcheck) showed a statistically significant 1.16-point rise for the whole sample
      over the survey period. There was a significant difference in mean food score
      change between health check attenders and non-attenders (Mann-Whitney U test: P <
      0.002). Maintenance of dietary improvement over a 2-year period was not affected
      by health check attendance. CONCLUSIONS: This study confirms the low impact of
      health checks on the self reported modification of cardiovascular risk factors
      and shows that maintenance of appropriate health behaviour change is no more
      likely in those who have received a health check.

PMID- 8872094
TI  - Childhood vulvovaginitis and vaginal discharge in general practice.
AB  - OBJECTIVE: This study aims to examine the aetiology, clinical features and
      response to treatment of childhood vulvovaginitis in general practice. METHOD: A
      longitudinal survey of consecutive premenarchal patients presenting with
      vulvovaginitis and/or vaginal discharge in the course of normal consultations
      with a general practitioner was conducted in a semi-rural, group general practice
      with 11,000 patients in Plymouth, UK. Forty-two premenarchal girls with vaginal
      inflammation or discharge were surveyed, with main outcome measures being
      clinical evaluation, microbiological assessment of urine and vaginal swabs, and
      patients' and parents' assessments of resolution and relapse of symptoms.
      RESULTS: Non-specific vulvovaginitis with mixed bacterial flora, associated with
      poor hygiene and atrophic vaginal mucosa, was the commonest cause; specific
      bacteria were found in 10 out of 42 cases, including six of Streptococcus
      pyogenes. No candida was isolated. Treatment with topical oestrogen cream was
      effective only with mixed infection, oral antibiotics were effective in both
      mixed and single organisms. No evidence of sexual abuse nor foreign body was
      found. CONCLUSION: Childhood vulvovaginitis is not uncommon in general practice,
      is usually associated with mixed growth of faecal organisms, and is seldom due to
      serious causes such as sexual abuse or foreign body.

PMID- 8872095
TI  - Where have all the back pains gone? Changes in the reasons for requiring out-of
      hours medical care from a centralized primary care centre after changing to a
      list system.
AB  - OBJECTIVE: We aimed to study changes in reasons for seeking assistance during out
      of-hours work in a single health centre before and after introduction of the list
      system. METHOD: A questionnaire concerning all out-of-hours general practice
      consultations for 1 week each month in two separate years (in 1990 and 1993) was
      completed in one health centre in central Finland (Palokka health centre) in a
      region with 39,465 inhabitants (37,960 inhabitants in 1990). All patients
      contacting the health centre to request medical help during out-of-hours work
      were asked to complete the questionnaire. Outcome measures were consultation
      rates by ICPC main codes. RESULTS: The annual out-of-hours consulting rate per
      1000 inhabitants decreased from 823 to 533 (35%) (P < 0.001). The clearest
      decrease (57%) from 172 to 74 consultations per 1000 inhabitants occurred in
      patients with musculoskeletal problems. A marked reduction (75%; from 52 to 13
      consultations per 1000 inhabitants) was found in male patients with back
      symptoms. For female patients with neck problems the reduction of out-of-hours
      consultations was also marked (67% reduction; from 12 to 4 consultations per 1000
      inhabitants). CONCLUSION: Improvement of continuity of care for patients having
      musculoskeletal problems is partly a question of organization, and it is also
      economically justifiable.

PMID- 8872096
TI  - Patterns of help-seeking behaviour for toddlers from two contrasting socio
      economic groups: new evidence on a neglected topic.
AB  - OBJECTIVE: This descriptive study aimed to assess patterns in help-seeking
      behaviour for common childhood symptoms. METHOD: Clinic attenders aged 9-18
      months of two child health clinics on Tyneside, UK, one with substantial economic
      deprivation, were studied. Outcome measures were parental reporting of common
      symptoms, utilization of professional advice and general practitioner records of
      consultations. RESULTS: Children in the affluent area had had fewer general
      practitioner consultations (mean 7.3) than those in the poorer area (mean 15.1;
      95% CI for difference 4.3-11.4). They were less likely to present with an episode
      of diarrhoea or cold but were as likely as the poorer group to present with
      fever. Behaviour problems were reported less frequently (23% versus 47%), but if
      present, this was far more likely to result in help seeking than in the poorer
      group (86% versus 33%; P < 0.05). CONCLUSIONS: Variations in help-seeking
      behaviour between two economically contrasting groups were identified; this has
      implications for clinical understanding and service provision in primary care.

PMID- 8872097
TI  - Socio-economic status, chronic morbidity and health services utilization by
      families.
AB  - BACKGROUND: This study deals with the perception of the burden of chronic
      morbidity in general practice. A married couple of general practitioners work in
      two primary health centres in Madrid (Spain), with populations of different socio
      economic status: one deprived, another of medium and high class. OBJECTIVE: The
      couple try to understand their feelings about a higher prevalence and severity of
      chronic morbidity in the poor district. METHOD: A transversal observational study
      was designed. A total of 119 patients aged 50-70 years were interviewed after the
      medical encounter. Data were obtained about (i) patients' sociodemographic
      conditions; (ii) structure and economic status of the families; and (iii) chronic
      morbidity and health services utilization of family members. RESULTS: Families in
      the deprived district included members of more than two generations in 76.5% of
      cases (18.8% in the comparison district); 70.3% of the heads of the families
      (main economic support) were pensioners in the poor district (23.7% in the
      comparison district); patients in the deprived district have more contacts with
      the health system and more chronic morbidity; families in the poor area have less
      expressiveness and cohesion and more irritability and negation. CONCLUSION:
      Perceived morbidity in general practice is a mix of social and family problems as
      well as number and severity of chronic health problems and health services
      utilization.

PMID- 8872098
TI  - Evaluation of general practice care by chronically ill patients: effect of the
      method of administration.
AB  - BACKGROUND: Although the patient survey has become a popular method for learning
      about patients' views and experiences, little attention has been paid to the
      validity and feasibility of different survey methods. OBJECTIVE: A study was
      undertaken to compare handing out written questionnaires to chronically ill
      patients who consecutively visited the general practice with mailing
      questionnaires to chronically ill patients who were sampled from the patient
      register. METHOD: Patient surveys were performed in eight general practices in
      The Netherlands, applying both methods of administering the questionnaire to
      patients in each practice (n = 345). RESULTS: The response rate was 63% in the
      mail survey and 72% in the hand-distributed survey. The sample composition was
      almost equal, except that patients in the hand-distributed survey more often
      reported having 'a different chronic disease.' The item-response for each aspect
      of care was similar in both methods of administration. CONCLUSION: Patients in
      the mail survey tended to use the extreme categories on the scale for certain
      aspects of care more often than patients in the hand-distributed survey, but the
      overall trend was not significant.

PMID- 8872099
TI  - ICPC as a standard classification in Norway.
AB  - BACKGROUND: The International Classification for Primary Care (ICPC) has been the
      standard classification for diagnoses on sickness certificates and bills for
      services to the National Insurance Administration in Norway since 1992. Coding
      according to ICPC is compulsory for all general practitioners. OBJECTIVE: The
      objective of the present study was to describe the introduction of ICPC in
      Norway, to comment on introduction problems, and to examine the compliance and
      validity of coding. METHODS: The study was based on statistics for episodes of
      sickness certification in the National Benefit Absence Register. RESULTS: In
      1994, the underlying medical diagnosis was coded in 98% of the sickness absence
      episodes lasting more than 2 weeks. Component 1 codes (symptom codes) were used
      in 23% of episodes, compared with 26-31% in practice studies. CONCLUSIONS: ICPC
      coded data in a large Norwegian register appear promising. Most doctors do
      accurate and careful work in coding, and data appear to be of acceptable quality
      for further analysis. It is a matter of concern, however, that as many as 23% of
      episodes had component 1 codes, since these certificates were issued during
      follow-up encounters. The introduction of ICPC coding has enabled researchers to
      use diagnoses in the analyses of sickness absence. The growing use of ICPC in
      general practice has made multi-practice studies possible. The introduction of
      criteria is mandatory for the improvement of validity in diagnostic coding.

PMID- 8872100
TI  - The uses and abuses of meta-analysis.
AB  - Meta-analysis is a quantitative process of summary and interpretation which
      involves pooling information from independent studies concerning a single theme
      in order to draw conclusions. Greatly increased employment of meta-analysis is
      currently being advocated for clinical and policy decision making. However, the
      prestige of meta-analysis is based upon a false model of scientific practice.
      Interpreting empirical research is an extremely complex activity requiring
      clinical and scientific knowledge of the field in question; and teams of
      professional 'meta-analysts' with a primary skill base in information technology
      and biostatistics cannot take over this role. Meta-analysis is not a hypothesis
      testing activity, and cannot legitimately be used to establish the reality of a
      putative hazard or therapy. The proper use of meta-analysis is to increase the
      precision of quantitative estimates of health states in populations. If used to
      estimate an effect, the reality of that effect should have been established by
      previous scientific studies. But the summary estimate from a meta-analysis can
      only be directly applied to a target population when the 'meta-protocol' and
      'meta-population' match the target situation in all relevant particulars. These
      constraints can rarely be satisfied in practice, so the results of meta-analysis
      typically require adjustment--which is a complex, assumption-laden process that
      negates many of the statistical power advantages of a meta-analysis. Lacking any
      understanding or acknowledgement of the need for adjustment, most meta-analyses
      must be regarded as abuses of the technique.

PMID- 8872101
TI  - Design and analysis of studies evaluating smoking cessation interventions where
      effects vary between practices or practitioners.
AB  - BACKGROUND: Patients grouped together in practices may share characteristics that
      cause them to have similar responses to an intervention. Sampling from such
      groups means that the power of a trial is less than when subjects are selected
      from the population at random. Knowledge of likely variation in outcome at the
      practice level is necessary to calculate the extent to which sample size would
      need to be inflated to maintain statistical power in the face of 'cluster
      effects'. OBJECTIVES: To plan sample size and precision requirements of a
      clinical trial, we examined reports of primary care smoking cessation trials for
      information on outcomes at the level of clusters, and found them unhelpful. We
      therefore constructed hypothetical scenarios to quantity the potential importance
      of this effect. METHOD: Scenarios of moderate and large inter cluster variation
      were compared with a sample where there was no difference in effect size at the
      level of practices. RESULTS: A study with 80% power to detect a difference of 20%
      versus 10% at a 5% significance level would need 200 patients in each arm in the
      absence of cluster effects. With moderate variation in outcome between clusters,
      over a thousand patients would be needed in the study to maintain this precision.
      With larger inter-cluster variation, close to 4000 subjects would be required.
      CONCLUSIONS: In the absence of detailed data from previous studies, hypothetical
      models can give insight into the statistical implications of possible cluster
      effects on study design and analysis. With even moderate inter-cluster variation,
      sample size will have to be inflated considerably to maintain the same
      statistical precision. Workers in this field will greatly assist those planning
      future research if they publish details of variation in outcome at the level of
      clusters.

PMID- 8872102
TI  - Selections from current literature: clinical detection of abuse.

PMID- 8872103
TI  - Workshop to establish databases of carbohydrate spectra.

PMID- 8872104
TI  - Aglycone modulation of glycolipid receptor function.
AB  - The aglycone has been largely ignored in consideration of glycoconjugate
      function. Evidence is reviewed which suggests that the role of the lipid in
      glycolipid carbohydrate function may be particularly significant. The lipid
      moiety can promote or reduce carbohydrate exposure of membrane glycolipids.
      Theoretical calculation has indicated that the plane of the plasma membrane can
      restrict the permitted conformations of a given glycolipid oligosaccharide. Thus
      the lipid moiety may influence the relative conformation of such carbohydrate
      sequences. Evidence of ceramide regulation of glycolipid function can be found in
      studies of enzyme substrate specificity, antiglycolipid recognition and
      bacterial/host cell interactions. Studies of verotoxin binding to its glycolipid
      receptor globotriaosyl ceramide indicate that modulation of receptor function by
      glycolipid fatty acid content plays an important role in in vitro binding assays,
      cell cytotoxicity and intracellular routing.

PMID- 8872105
TI  - Aberrant glycosylation of IgA from patients with IgA nephropathy.
AB  - Despite the prominent role of IgA, particularly IgA1, in the pathogenesis of IgA
      nephropathy (IgAN), the precise role of this molecule in the process remains
      unclear. Four biotin-conjugated lectins in sandwich-type enzyme-linked
      immunosorbent assays were devised to determine the glycosylation profiles of
      total IgA and its subclasses. We took advantage of differential binding
      properties of these lectins to sugar residues to dissect the oligosaccharide
      chains O-linked to the hinge and those N-linked to the Fc region of total IgA and
      IgA subclasses in 47 patients with IgAN and an equal number of controls. The
      proportion of sialylated IgA1 was higher in patients compared with controls (p <
      0.02), whereas IgA2 in patients appeared less well sialylated. A reduction of
      galactose in pathological IgA as detected by RCA-I became significant after
      treatment of the molecule with neuraminidase (p < 0.01). Defective
      galactosylation was also observed for patient IgA1 when it was probed with ECL, a
      lectin that has a specificity for Gal 1,4 N-acetylglucosamine groupings on N
      linked oligosaccharides. The RCA and ECL results, therefore, suggest that
      increased sialylation on the IgA1 is on O-linked oligosaccharides in the hinge
      region. This was partly confirmed by a small increase in the binding of PNA to
      IgA1 from the patient group. This lectin binds preferentially to Gal 1,3 N
      acetylgalactosamine groups that are found on O-linked oligosaccharides.

PMID- 8872106
TI  - An antibody-lectin sandwich assay for the determination of CA125 antigen in
      ovarian cancer patients.
AB  - A two-step forward sandwich assay was developed for the determination of the
      ovarian tumour associated glycoconjugate antigen CA125 with anti-CA125 Monoclonal
      antibody B27.1 on the solid phase and 125I-labelled wheat germ lectin as tracer
      in the solution phase. This Mab-lectin heterosandwich assay was optimized and the
      clinical utility was evaluated in sera from healthy volunteers and ovarian cancer
      patients. A correlation was established between Mab-lectin assay and the dual
      monoclonal antibody sandwich assay, TRUQUANTOV2 RIA, that uses the same MAb B27.1
      on the solid phase and a second 125I-labelled B43.13 MAb in the solution phase. A
      potentially improved clinical utility is suggested for the Mab-lectin assay. The
      unique format seems to identify novel isoforms of CA125 with different
      carbohydrate side chains that would otherwise be undetectable in the MAb-MAb
      sandwich assay wherein the paratopes are likely directed to protein determinants.

PMID- 8872107
TI  - Free alanine, aspartic acid, or glutamic acid reduce the glycation of human lens
      proteins.
AB  - The amino acids lysine and glycine are reported to react with glucose at
      physiological pH and temperature and undergo non-enzymic glycation. Three other
      amino acids present in relatively larger amounts in the lens i.e. alanine,
      aspartic acid and glutamic acid were also found to undergo non-enzymic glycation
      as found by incorporation of uniformly labelled (U-[14C]) glucose into the amino
      acids. The glucose incorporation was 1.6 to 2.5% for alanine, 35 to 50% for
      aspartic acid and 2.3 to 3.3% for glutamic acid. Each amino acid of varying
      concentrations lowered the extent of in vitro glycation of lens proteins
      significantly in glucose-treated homogenates of normal lens from humans. The
      decrease in glycation for alanine was between 32 and 69%, that for aspartate was
      between 18 and 74%, and for glutamate was between 52 to 74%. Decreased glycation
      was greater for higher concentrations of glucose. Scavenging of intracellular
      glucose and decreasing the extent of glycation of lens proteins could be the
      mechanism of action by which the amino acids alanine, aspartic acid and glutamic
      acid could exercise a beneficial effect on cataract and diabetic retinopathy.

PMID- 8872108
TI  - Evidence for a correlation between ambient cholesterol levels and soluble plasma
      sialyltransferase enzyme activity.
AB  - While soluble forms of the sialyltransferase (sialyl-T) enzyme have been detected
      in significant quantities in serum, the exact source(s) of the enzyme, or the
      factors controlling its secretion are poorly understood. In this study, we have
      examined the relationship between ambient plasma cholesterol concentrations and
      sialyl-T-activities and also levels of constituent plasma sialoglycoproteins
      (SGP). There was an inverse relationship between levels of the alpha 2, 6 sialyl
      T enzyme and both total plasma cholesterol and HDL, although no such relationship
      was observed for the alpha 2,3 enzyme. While there was no correlation between
      total cholesterol and the levels of plasma SGPs, there was an inverse
      relationship between the HDL component and alpha 2,3 SGPs.

PMID- 8872109
TI  - Histo-blood group p: biosynthesis of globoseries glycolipids in EBV-transformed B
      cell lines.
AB  - The genetic and biosynthetic basis of the histo-blood group P-system is not fully
      understood. Individuals with the rare p phenotype do not express the three
      glycolipid antigens (Pk, P and P1) of this system, probably because of
      deficiencies in glycosyltransferases involved in their biosynthesis. Iiuka et al.
      [Iiuka S, Chen SH, Yoshida A (1986) Biochem Biophys Res Commun 137: 1187-95],
      however, previously reported that detergent extracts from an EBV-transformed B
      cell line derived from a p individual did express the glycosyltransferase
      activity (Pk transferase) assumed to be missing in this blood group status. Here,
      we have reinvestigated the antigen expression and glycosyltransferase activities
      in two p individuals by analysing EBV-transformed cell lines as well as
      erythrocytes to confirm the blood group P status. The thin layer chromatography
      glycolipid profile of extracts from erythrocytes and EBV-transformed B cell lines
      showed characteristic accumulation of lactosylceramide and absence of Pk and P
      antigens. Glycosyltransferase activities of the B cell lines were analysed using
      glycolipid substrates and both extracts were found to contain lactosylceramide
      synthetase and P transferase activities but to be completely devoid of Pk
      transferase activity. The presented data indicate that p individuals, in contrast
      to previous reports, do not express a functional Pk glycosyltransferase.

PMID- 8872110
TI  - Ethnic differences in the expression of blood group antigens in the salivary
      gland secretory cells from German and Japanese non-secretor individuals.
AB  - Type 1 ABO blood group antigens (peripheral core structure: Gal beta 1-3GlcNAc
      beta 1-R) are expressed mainly in endodermally-derived tissues, but are not
      synthesized in mesodermally-derived tissues. In the former tissues, H type 1
      antigen is generated largely by alpha-2-L-fucosyltransferase encoded by secretor
      (Se) gene and acting on the terminal galactose of the type 1 precursor chain.
      This theory has been generally accepted, and it seems that the expression of ABO
      blood group antigens is absent, or expressed at a low level, in these tissues
      from non-secretor individuals. In this immunohistochemical study on the secretory
      cells of salivary glands, we found ethnic difference between German and Japanese
      non-secretor individuals in the expression of blood group antigens: i.e. the
      expression of the type 1 blood group antigens is present in these cells from
      Japanese non-secretor individuals but absent from German. A possible explanation
      is that another alpha-2-L-fucosyltransferase, independent of the secretor gene,
      is present in Japanese non-secretor individuals.

PMID- 8872111
TI  - Ceramide-1-phosphate sugars: new types of glycophospholipids.
AB  - Ceramide-1-phosphate sugars were synthesized by direct glycosyl
      phosphite/phosphate and O-glycosyl trichloroacetimidate/phosphate exchange
      reactions, respectively. Thus, ceramide-1-O-phosphoric acid 5 gave with sialyl
      phosphite 1 as sialyl donor directly beta-linked sialyl phosphate 6; deprotection
      afforded the corresponding glycophospholipid ceramide-1-phosphate N
      acetylneuraminate 7. Similarly, from O-glucosyl- and O
      galactosyltrichloroacetimidate 10 and 13 with phosphoric acid derivative 5
      glycosyl ceramide-1-phosphate sugars 12 and 15, respectively, were obtained.

PMID- 8872112
TI  - Structures and contribution to the antigenicity of oligosaccharides of Japanese
      cedar (Cryptomeria japonica) pollen allergen Cry j I: relationship between the
      structures and antigenic epitopes of plant N-linked complex-type glycans.
AB  - The oligosaccharide structures of Cry j I, a major allergenic glycoprotein of
      Cryptomeria japonica (Japanese cedar, sugi), were analysed by 400 MHz 1H-NMR and
      two-dimensional sugar mapping analyses. The four major fractions comprised a
      series of biantennary complex type N-linked oligosaccharides that share a
      fucose/xylose-containing core and glucosamine branches including a novel
      structure with a nongalactosylated fucosylglucosamine branch. Rabbit polyclonal
      anti-Cry j I IgG antibodies cross-reacted with three different plant
      glycoproteins having the same or shorter N-linked oligosaccharides as Cry j I.
      ELISA and ELISA inhibition studies with intact glycoproteins, glycopeptides and
      peptides indicated that both anti-Cry j I IgGs and anti-Sophora japonica bark
      lectin II (B-SJA-II) IgGs included oligosaccharide-specific antibodies with
      different specificities, and that the epitopic structures against anti-Cry j I
      IgGs include a branch containing alpha 1-6 linked fucose and a core containing
      fucose/xylose, while those against anti-B-SJA-II IgGs include nonreducing
      terminal mannose residues. The cross-reactivities of human allergic sera to
      miraculin and Clerodendron Trichotomum lectin (CTA) were low, and inhibition
      studies suggested that the oligosaccharides on Cry j I contribute little or only
      conformationally to the reactivity of specific IgE antibodies.

PMID- 8872113
TI  - Constitutively hyposialylated human T-lymphocyte clones in the Tn-syndrome:
      binding characteristics of plant and animal lectins.
AB  - Previously, beta 1,3-galactosyltransferase-deficient (Tn+) and normal (TF+) T
      lymphocyte clones have been established from a patient suffering from Tn-syndrome
      [Thurnher et al. (1992) Eur J Immunol 22: 1835-42]. Tn+ T lymphocytes express
      only Tn antigen GalNAc alpha 1-O-R) while other O-glycan structures such as
      sialosyl-Tn (Neu5Ac alpha 2,6GalNAc alpha 1-O-R) or TF (Gal beta 1-3GalNAc alpha
      1-O-R) antigens are absent from these cells as shown by flow cytometry using
      specific mABs for TF and sialosyl-Tn antigen, respectively. Normal T lymphocytes
      express the TF antigen and derivatives thereof. The surface glycans of Tn+ and
      TF+ cells were then analysed by flow cytometry using the following sialic acid
      binding lectins: Amaranthus caudatus (ACA), Maackia amurensis (MAA), Limax flavus
      (LFA), Sambucus nigra (SNA) and Triticum vulgare (WGA). Equal and weak binding of
      MAA and SNA to both TF+ and Tn+ cells was found. WGA, LFA and ACA bound more
      strongly to TF+ cells than to Tn+ cells. Binding of ACA to TF+ cells was enhanced
      after sialidase treatment. To investigate the possible biological consequences of
      hyposialylation, binding of three sialic acid-dependent adhesion molecules to Tn+
      and TF+ cells was estimated using radiolabelled Fc-chimeras of sialoadhesin (Sn),
      myelin-associated glycoprotein (MAG) and CD22. Equal and strong binding of human
      CD22 to both TF+ and Tn+ cells was found. Whereas binding of Sn and MAG to TF+
      cells was strong (100%), binding to Tn+ cells amounted only to 33% (Sn) and 19%
      (MAG). These results indicate that the in vivo interactions of T lymphocytes in
      the Tn syndrome with CD22 are not likely to be affected, whereas adhesion
      mediated by Sn or MAG could be strongly reduced.

PMID- 8872114
TI  - Post-translational proteolytic processing and the isolectins of lentil and other
      Viciae seed lectins.
AB  - Electrospray mass spectrometry was used to identify precisely the proteolytic
      cleavage points within, and at the C-termini of, the proprotein forms of four
      Viciae lectins that give rise to their two-chain forms. The lectins examined were
      the pea and lentil lectins, favin and the Lathyrus odoratus lectin, which
      represent each of the four genera in this tribe. The molecular mass data showed
      single beta-chain forms for each lectin, with masses consistent with the
      available sequence and glycopeptide data, indicating that each came from a single
      proprotein. In contrast, the pea, lentil and L. odoratus alpha-chains occurred in
      as many as five forms, due to multiple C-terminal cleavage points. Only favin
      showed a single alpha-chain form. The alpha-chain mass data were again consistent
      with the sequence information available, except for the lentil lectin alpha-chain
      which was re-determined by protein sequencing. The two isolectin forms of this
      protein were shown to arise from alpha-chain species with and without residue
      Lys53. The mass spectrum of concanavalin A was also examined and both the single
      chain form and the two fragment forms showed no evidence of C-terminal
      heterogeneity.

PMID- 8872115
TI  - Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA)
      in comparison to Ulex europaeus agglutinin I (UEA-I).
AB  - Using immunochemical and immunohistochemical methods, the binding site of
      Anguilla anguilla agglutinin (AAA) was characterized and compared with the
      related fucose-specific lectin from Ulex europaeus (UEA-I). In solid-phase enzyme
      linked immunoassays, the two lectins recognized Fuc alpha 1-2Gal beta-HSA. AAA
      additionally cross-reacted with neoglycolipids bearing lacto-N-fucopentaose
      (LNFP) I [H type 1] and II [Le(a)] and lactodifucotetraose (LDFT) as glycan
      moieties. UEA-I, on the other hand, bound to a LDFT-derived neoglycolipid but not
      to the other neoglycolipids tested. Binding of AAA to gastric mucin was
      competitively neutralized by Le(a)-specific monoclonal antibodies. UEA-I binding,
      on the other hand, was reduced after co-incubation with H type 2- and Le(y)
      specific monoclonal antibodies. According to our results, AAA reacts with
      fucosylated type 1 chain antigens, whereas UEA-I binds only to the alpha 1-2
      fucosylated LDFT-derived neoglycolipid. In immunohistochemical studies, the
      reactivity of AAA and UEA-I in normal pyloric mucosa from individuals with known
      Lewis and secretor status was analysed. AAA showed a broad reaction in the
      superficial pyloric mucosa from secretors and non-secretors, but AAA reactivity
      was more pronounced in Le(a+b-) individuals. On the other hand, UEA-I stained the
      superficial pyloric mucosa only from secretor individuals. A staining of deep
      mucous glands by the lectins was found in all specimens. Both reacted with most
      human carcinomas of different origin. Slight differences in their binding pattern
      were observed and may be explained by the different fine-specificities of the
      lectins.

PMID- 8872116
TI  - Galectin-1 is expressed by thymic epithelial cells in myasthenia gravis.
AB  - Galectin-1, a member of a family of carbohydrate binding proteins, is synthesized
      by thymic epithelial cells in normal juvenile thymus, and mediates adhesion of
      immature T cells to thymic epithelium. Because cell adhesion molecules are
      proposed to play a role in the thymic hyperplasia and neoplasia seen in the
      autoimmune disease myasthenia gravis, we examined the expression of galectin-1 in
      myasthenic thymi. We detected abundant galectin-1 expression in thymic epithelial
      cells in 27 hyperplastic and neoplastic thymi from patients with myasthenia
      gravis. Primary cultures of neoplastic epithelial cells from a thymoma continued
      to express galectin-1, and bound immature T cells; T cell binding was inhibited
      by the addition of the beta-galactosides lactose and thiodigalactoside,
      suggesting that galectin-1 on the thymoma cells and a saccharide ligand on the T
      cells participated in cell-cell adhesion. Expression of galectin-1 by thymic
      epithelial cells may play a role in the thymic pathology seen in myasthenia
      gravis.

PMID- 8872117
TI  - Complete 1H NMR assignments of synthetic glycopeptides from the carbohydrate
      protein linkage region of serglycins.
AB  - We present complete 1H NMR assignments for two synthetic glycopeptides
      representative of the carbohydrate-protein linkage region of serglycin
      proteoglycans. The peptides are: Ser(Galp-Xylp)-Gly-Ser-Gly-Ser(Galp-Xylp)-Gly
      and, Ser(Galp-Xylp)-Gly-Ser(Galp-Xylp)-Gly-Ser(Galp-Xylp)-G ly. A number of 2D
      NMR spectra together with a 3D NOESY-TOCSY spectrum were acquired at 600 MHz to
      complete the assignments of the glycopeptides dissolved in water with 40%
      trifluoroethanol. Preliminary analysis of the NMR data suggests folded structures
      for the glycopeptides.

PMID- 8872118
TI  - Preparation of a series of sulfated tetrasaccharides from shark cartilage
      chondroitin sulfate D using testicular hyaluronidase and structure determination
      by 500 MHz 1H NMR spectroscopy.
AB  - Six tetrasaccharide fractions were isolated from shark cartilage chondroitin
      sulfate D by gel filtration chromatography followed by HPLC on an amine-bound
      silica column after exhaustive digestion with testicular hyaluronidase. Their
      structures were determined unambiguously by one- and two-dimensional 500 MHz 1H
      NMR spectroscopy in conjunction with HPLC analysis of chondroitinase AC-II
      digests of the tetrasaccharides. One fraction was found to contain two
      tetrasaccharide components. All of the seven tetrasaccharides shared the common
      core structure GlcA beta 1-3GalNAc beta 1-4GLcA beta 1-3GalNAc with various
      sulfation profiles. Four were disulfated comprising of two monosulfated
      disaccharide units GLcA beta 1-3GalNAc(4-sulfate) and/or GlcA beta 1-3GalNAc(6
      sulfate), whereas the other three were hitherto unreported trisulfated
      tetrasaccharides containing a disulfated disaccharide unit GlcA(2-sulfate)beta 1
      3GalNAc(6-sulfate) and a monosulfated disaccharide unit GlcA beta 1-3GalNac(4- or
      6-sulfate). These sulfated tetrasaccharides were demonstrated to serve as
      appropriate acceptor substrates for serum alpha-N
      acetylgalactosaminyltransferase, indicating their usefulness as authentic
      oligosaccharide substrates or probes for the glycobiology of sulfated
      glycosaminoglycans.

PMID- 8872119
TI  - Binding specificity of influenza C-virus to variably O-acetylated glycoconjugates
      and its use for histochemical detection of N-acetyl-9-O-acetylneuraminic acid in
      mammalian tissues.
AB  - The specificity of influenza C-virus binding to sialoglycoconjugates was tested
      with various naturally O-acetylated gangliosides or synthetically O-acetylated
      sialic acid thioketosides, which revealed binding to 9-O-acetylated N
      acetylneuraminic acid. Binding was also observed with a sample of Neu5,7Ac2-GD3,
      however at a lower degree. Sialic acids with two or three O-acetyl groups in the
      side chain of synthetic sialic acid derivatives are not recognized by the virus.
      In these experiments, bound viruses were detected with esterase substrates.
      Influenza C-virus was also used for the histological identification of mono-O
      acetylated sialic acids in combination with an immunological visualization of the
      virus bound to thin-sections. The occurrence of these sialic acids was
      demonstrated in bovine submandibular gland, rat liver, human normal adult and
      fetal colon and diseased colon, as well as in human sweat gland. Submandibular
      gland and colon also contain significant amounts of glycoconjugates with two or
      three acetyl esters in the sialic acid side chain, demonstrating the value of the
      virus in discriminating between mono- and higher O-acetylation at the same site.
      The patterns of staining showed differences between healthy persons and patients
      with colon carcinoma, ulcerative colitis or Crohn's disease. Remarkably, some
      human colon samples did not show O-acetyl sialic acid-specific staining. The
      histochemical observations were controlled by chemical analysis of tissue sialic
      acids.

PMID- 8872120
TI  - An approach for fluorometric determination of glycosyltransferase activities.
AB  - A new strategy for the fluorometric determination of glycosyltransferase
      activities is reported. The method involves dansyl chloride derivatization of the
      reduced form (pNH2phenyl) of a hydrophobic, aglycon moiety covalently linked to a
      number of acceptor substrates (pNO2phenyl). Focusing on the Golgi enzyme core 2 N
      acetyl-glucosaminyltransferase, we found that synthesis and fractionation of the
      dansylated substrate derivative were rapid, easy and inexpensive. Additionally,
      the corresponding enzyme assay proved reproducible and very sensitive, as 0.4
      pmol of reaction product were readily detected. This fluorometric approach
      appears therefore to be a valid tool for investigating the monitoring
      differential expression of glycosyltransferases exhibiting low levels of enzyme
      activity.

PMID- 8872121
TI  - Detection of human asialo-alpha(1)-acid glycoprotein using a heterosandwich
      immunoassay in conjunction with the light addressable potentiometric sensor.
AB  - Highly specific detection of human alpha 1-acid glycoprotein (AGP) and asialo
      alpha 1-acid glycoprotein (asialo-AGP) was made possible by use of a sandwich
      immunoassay. The glycoproteins were sandwiched between biotinylated and
      fluoresceinated polyclonal rabbit anti-human AGP antibodies. Additionally, asialo
      AGP could be distinctly detected, apart from AGP, via the formation of a
      heterosandwich immunoassay using biotinylated polyclonal rabbit anti-human AGP
      and the lectin, fluoresceinated ricin toxin. Streptavidin was added to the formed
      immunocomplexes and the immunocomplexes captured on a biotinylated nitrocellulose
      membrane. The signal generator, urease conjugate of an anti-fluorescein antibody,
      was then bound to the complex on the membrane. The rate of pH change under
      microvolume conditions (0.6 microliters) was monitored using a silicon chip
      based, light addressable potentiometer sensor. Results indicated that AGP and
      asialo-AGP can be detected to the 2 pg level when two antibodies are used to form
      the immunocomplex. Asialo-AGP can be detected down to 250 pg when the
      heterosandwich immunoassay is used; this assay exhibited no response up to 10 ng
      for native AGP or asialofetuin. Both immunoassays can be used to quantify the
      level of AGP and asialo-AGP in solution. Although the assay presented is very
      specific for AGP, asialo-AGP and terminal galactose, it is readily adaptable for
      the detection of any glycoprotein and terminal carbohydrate (or branched
      structure) by use of a protein-specific antibody and various lectins.

PMID- 8872122
TI  - Transfer of Man9GlcNAc to L-fucose by endo-beta-N-acetylglucosaminidase from
      Arthrobacter protophormiae.
AB  - We have reported that transglycosylation activity of endo-beta-N
      acetylglucosaminidase from Arthrobacter protophormiae (endo-A) can be enhanced to
      near completion using GlcNAc as an acceptor in a medium containing 30% acetone
      (Fan J-Q, Takegawa K, Iwahara S, Kondo A, Kato I, Abeygunawardana C, Lee YC
      (1995) J Biol Chem 270: 17723-29). In this paper, we found that the endo-A can
      also transfer an oligosaccharide, Man9GlcNAc, to L-Fuc using Man9GlcNAc2Asn as
      donor substrate in a medium containing 35% acetone. The transglycosylation yield
      was greater than 25% when 0.2 M L-Fuc was used as acceptor. The
      transglycosylation produce was purified by high performance liquid chromatography
      on a graphitized carbon column and the presence of L-Fuc was confirmed by sugar
      composition analysis and electrospray mass spectrometry. Sequential exo
      glycosidase digestion of pyridyl-2-aminated transglycosylation product,
      Man9GlcNAc-L-Fuc-PA, revealed that a beta-anomeric configuration linkage was
      formed between GlcNAc and L-Fuc. The GlcNAc was found to be 1,2-linked to L-Fuc
      by two methods: i) collision-induced decomposition on electrospray mass
      spectrometry after periodate oxidation, reduction and permethylation of
      Man9GlcNAc-L-Fuc; and ii) preparation of Man9GlcNAc-L-Fuc-PA, its periodate
      oxidation and reduction, followed by hydrolysis and HPLC analysis. Thus, the
      structure of the oligosaccharide synthesized by endo-A transglycosylation was
      determined to be Man9GlcNAc beta (1,2)-L-Fuc. Methyl-beta-L-fucopyranoside, L-Gal
      are also acceptors for the enzymic transglycosylation. However,
      transglycosylation failed when methyl alpha-L-fucopyranoside, D-Fuc and D-Gal
      were used. These results indicate that the endo-A requires not only 3-OH and 4-OH
      to be equatorial but also a 4C1-conformation or equivalent conformation of the
      acceptor to perform transglycosylation.

PMID- 8872123
TI  - Purification and characterization of Kurloff cell sialoglycoproteins with acid
      phosphatase activity.
AB  - The major alpha 2-6 sialoglycoproteins in detergent-extracts of Kurloff cells
      were purified by anion-exchange and Sambucus nigra agglutinin-affinity
      chromatographies. The similar ultrastructural localisations of (1) S. nigra
      agglutinin-gold conjugates and (2) acid phosphatase activities on the Kurloff
      body and particularly on its myelin figures indicated that the major alpha 2-6
      sialoglycoproteins of the Kurloff cell had acid phosphatase activity. Two
      dimensional electrophoresis showed that these tartrate-sensitive phosphatases
      corresponded to 2 acidic (pI 3.4-3.7) polypeptides of 36 and 34 kDa. Hydrolysis
      with peptide-N-glycosidases F gave a 33 kDa apoprotein rich in alanine, glutamic
      acid, tyrosine and lysin. A lectin-affinity study demonstrated that they
      contained hybrid type bisected and fucosylated N-linked oligosaccharides.
      Cytotoxic properties were previously attributed to Kurloff cells and other
      studies suggested that not only acid phosphatases but also alpha 2-6-linked
      sialic acid residues themselves may participate in natural killer activity.

PMID- 8872125
TI  - Site of stimulation by mannosyl-P-dolichol of GlcNAc-lipid formation by
      microsomes of embryonic chick retina.
AB  - Mannosyl-P-dolichol (man-P-dol) has been shown to stimulate the early reactions
      of the dolichol pathway, specifically, the biosynthesis of GlcNAc-P-P-dol and
      GlcNAc-GlcNAc-P-P-dol, and thus may play a regulatory role in glycoprotein
      biosynthesis. The site of action of man-P-dol has previously been suggested to be
      the GlcNAc-transferase concerned with the formation of the monoglucosaminyl
      derivative. Since the concentration of the chitobiosyl compound also increases as
      a result of the presence of man-P-dol, the immediate site of the activation was
      reexamined. The effect of man-P-dol on the formation of GlcNAc-GlcNAc-P-P-dol
      using GlcNAc-P-P-dol synthesized in situ or added exogenously as the substrate
      was investigated. In addition, the distribution of radioactivity in the
      glucosaminyl constituents of the products under the stimulatory conditions was
      determined. The results of these studies supported the conclusion that the
      stimulation of GlcNAc-lipid synthesis by man-P-dol is due to the enhanced
      synthesis of GlcNAc-P-P-dol. It is not a result of the activation of the GlcNAc
      transferase catalyzing the attachment of the second GlcNAc residue for the
      biosynthesis of the chitobiosyl derivative.

PMID- 8872124
TI  - Inhibition of human HT-29 colon carcinoma cell adhesion by a 4-fluoro-glucosamine
      analogue.
AB  - Cell surface glycoconjugates play an important role in cellular recognition and
      adhesion. Modification of these structures in tumour cells could affect tumour
      cell growth and behaviour, including metastasis. 2-Acetamido-1,3,6-tri-O-acetyl-4
      deoxy-4-fluoro-alpha-D-glycopyranose (4-F-GlcNAc) was synthesized as a potential
      inhibitor and/or modifier of tumour cell glycoconjugates. The effect of this
      sugar analogue on the adhesive properties of human colon carcinoma HT-29 cells
      was evaluated. Treatment of HT-29 cells with 4-F-GlcNAc led to reduced cell
      surface expression of terminal lactosamine, sialy-Le(x) and sialyl-Le(a), as
      determined by Western blotting and flow cytometry. The aberrant expression of
      these oligosaccharide structures on the HT-29 cell surface resulted in: (1)
      decreased E-selectin mediated adhesion of human colon cells to human umbilical
      cord endothelial cells (HUVEC); (2) impaired adhesion of HT-29 cells to beta
      galactoside binding lectin, galectin-1; and (3) reduced ability to form homotypic
      aggregates. After exposure to 4-F-GlcNAc, lysosomal associated membrane proteins
      (lamp) 1 and 2, and carcinoembryonic antigen (CEA) detected in HT-29 cells were
      of lower molecular weight, probably due to impaired glycosylation. These results
      strongly suggest that modification of tumour cell surface molecules can alter
      tumour cell adhesion and that tumour cell surface oligosaccharides may be
      suitable targets for therapeutic exploitation.

PMID- 8872126
TI  - A novel method for glycoconjugate synthesis.
AB  - 2-Chloroethyl 1-thio-beta-D-galactopyranoside and the corresponding 1-thio-beta-D
      glucopyranoside have been found to be suitable glycosylating agents for the
      preparation of different types of glycoconjugates. Glycosylation of bovine serum
      albumin and chymotrypsin were chosen as examples of an application of the
      described compounds. The glycosylating agents can modify not only amino groups,
      but also alkyl hydroxyl and aryl hydroxyl groups, as was shown in experiments
      with model water soluble and water insoluble polyacrylamide copolymers.

PMID- 8872127
TI  - One-pot enzymatic synthesis of the Gal alpha 1-->3Gal beta 1-->4GlcNAc sequence
      with in situ UDP-Gal regeneration.
AB  - The trisaccharide Gal alpha 1-->3Gal beta 1-->4GlcNAc beta 1-->O-(CH2)8COOCH3 was
      enzymatically synthesized, with in situ UDP-Gal regeneration. By combination in
      one pot of only four enzymes, namely, sucrose synthase, UDP-Glc 4'-epimerase, UDP
      Gal:GlcNAc beta 4-galactosyltransferase and UDP-Gal:Gal beta 1-->4GlcNAc alpha 3
      galactosyltransferase, Gal alpha 1-->3Gal beta 1-->4GlcNAc beta 1-->O
      (CH2)8COOCH3 was formed in a 2.2 mumol ml-1 yield starting from the acceptor
      GlcNAc beta 1-->O-(CH2)8COOCH3. This is an efficient and convenient method for
      the synthesis of the Gal alpha 1-->3Gal beta 1-->4GlcNAc epitope which pays an
      important role in various biological and immunological processes.

PMID- 8872128
TI  - Influence of recombinant hirudin on tissue-factor-induced activation of
      coagulation in rabbits.
AB  - Uncontrolled activation of the tissue-factor (TF)-dependent extrinsic pathway of
      coagulation can lead to severe impairment of the hemostatic balance. AS thrombin
      plays the central role in the initiation of clotting, we used the highly specific
      thrombin inhibitor recombinant hirudin to prevent TF-induced coagulation
      activation in a rabbit model. Infusion of 0.5 micrograms.kg-1.h-1 TF in rabbits
      for 7 h led to a decrease in fibrinogen and platelets, to an increase in fibrin
      monomers and to a prolongation of TT, aPTT and PT. Recombinant hirudin was
      administered in doses of 0.5, 1 and 2 mg.kg-1 body weight (intravenous bolus),
      the protocol included a pre-TF (recombinant hirudin given at t = 0) and a post-TF
      study group (recombinant hirudin given at t = 2 h after the start of the TF
      infusion). Fibrinogen plasma levels, platelet counts and recombinant hirudin
      plasma levels were measured at baseline (t = 0) at 0.5, 1, 2, 3, 4, 5, 6, and 7
      h; the deceleration rate of fibrinogen and platelets per hour was calculated for
      the control and the recombinant-hirudin-treated groups. The deceleration rate for
      fibrinogen in the TF group was -0.227 g.l-1.h-1 and was reduced by recombinant
      hirudin to -0.119, -0.116 and -0.095 g.1-1.h-1 for 0.5, 1 or 2 mg.kg-1,
      respectively (significant differences to control group, Jonckheere-Terpstra
      test). The inhibitor similarly prevented the decrease of platelets dose
      dependently. Recombinant hirudin was cleared from plasma with a terminal half
      life of about 100 min; however, even after its clearance from plasma, recombinant
      hirudin significantly prevented the fibrinogen and platelet drop. Recombinant
      hirudin was effective when given in the pre-TF as well as in the post-TF phase.

PMID- 8872129
TI  - A recombinant hirudin (IK-HIR02) in healthy volunteers. II. Effects on platelet
      adhesion and platelet-induced thrombin generation time.
AB  - The pharmacodynamic effects of different intravenous and subcutaneous doses of a
      new recombinant hirudin (IK-HIR02) on platelet adhesion, platelet-induced
      thrombin formation and on platelet count have been studied in 18 healthy
      volunteers in a bicenter study. Single intravenous bolus injections of 0.1, 0.2
      and 0.3 mg/kg IK-HIR02 in 6 volunteers caused a significant dose-dependent
      prolongation of platelet-induced thrombin generation time (PITT) and a
      significant inhibition of platelet adhesion to glass. Single subcutaneous doses
      of 0.1, 0.25 and 0.5 mg/kg IK-HIR02 slightly prolonged PITT and inhibited
      platelet adhesion to glass for up to 8 h. Repeat subcutaneous injections of 0.3
      mg/kg IK-HIR02 b.i.d. in 6 healthy volunteers led to a prolongation of PITT and
      also to a reduction of platelet adhesion. In platelet-rich plasma (PRP) from
      blood samples which had been collected using hirudin as anticoagulant (0.7
      micrograms/ml), the platelet count was constantly higher than in citrate PRP
      which had been sampled at the same time. The recombinant hirudin IK-HIR02
      inhibits platelet adhesion to glass and also PITT. Both effects which have not
      been described before are most likely due to a direct inhibition of thrombin
      induced platelet activation. These effects may contribute to the antithrombotic
      action of hirudin and probably have to be considered when hirudin is used in
      higher doses as an antithrombotic agent together with platelet function
      inhibitors to avoid excessive bleeding.

PMID- 8872130
TI  - Protamine sulphate inhibits pentasaccharide (SR80027)-induced bleeding without
      affecting its antithrombotic and anti-factor Xa activity in the rat.
AB  - The neutralization of a potent anti-factor Xa pentasaccharide (SR 80027) and
      heparin-induced bleeding enhancement by protamine sulphate was studied in vivo.
      Bleeding time, as measured by transection of the tail of anaesthetized rats,
      increased after the administration of standard heparin and SR 80027. Doses of 0.6
      and 2.5 mg/kg of heparin and SR 80027, respectively, were required to enhance
      blood loss to the same extent (6-fold increase). Protamine sulphate (10 mg/kg
      i.v.) reduced blood loss induced by both compounds but also neutralized the anti
      factor Xa activity as well as the antithrombotic activity of standard heparin
      measured in a venous thrombosis model. However, protamine sulphate did not affect
      the anti-factor Xa activity or the antithrombotic activity of SR 80027. These
      data suggest that protamine sulphate may be an effective antidote for the
      bleeding side-effects of SR 80027 but they also indicate that the bleeding
      tendency associated with this type of compounds cannot be attributed to their
      anti-factor Xa activity.

PMID- 8872131
TI  - Comparison of hemorrhagic effect of heparin and human activated protein C with
      use of Thrombostat 4000.
AB  - The importance of bleeding as a complication of anticoagulant therapy is clearly
      recognized. We previously reported that amelioration of hemorrhage associated
      with disseminated intravascular coagulation by the human activated protein C
      (APC) was greater than that by heparin. In this study, we compared the bleeding
      complication of intravenously administered APC and heparin in rabbits, and also
      estimated primary hemostasis. When both anticoagulants were intravenously
      infused, the bleeding time from a punctured ear vein was prolonged dose
      dependently. However, at doses which prolonged the activated partial
      thromboplastin time nearly equally, the prolongation of bleeding was greater in
      heparin-administered rabbits. Blood withdrawn from heparin-administered animals
      showed increases in in vitro bleeding parameters which correlated with the in
      vivo bleeding time. However, only small changes were observed in the blood
      withdrawn from APC-administered animals. Both drugs induced either no change or
      only a slight decrease in the platelet count, hematocrit and fibrinogen content.
      These observations suggest that APC may be a more useful anticoagulant than
      heparin since it causes less bleeding tendency.

PMID- 8872132
TI  - Highly substituted hydroxyethyl starch (HES200/0.62) leads to Type-I von
      Willebrand syndrome after repeated administration.
AB  - Hydroxyethyl starch (HES) is a frequently used plasma substitute that is popular
      due to a high degree of therapeutic safety. However, the administration of large
      volumes of highly substituted, high-molecular-weight starch often leads to
      iatrogenic von Willebrand syndrome (vWS) with hemorrhagic complications. In
      patients with cerebral circulatory disturbances we carried out hemodilution
      therapy during 9-10 days, infusing HES 200/0.62. A von Willebrand factor (vWF)
      multimeric analysis was carried out in 6 patients using a modified western blot
      according to the sodium dodecyl sulfate agarose gel electrophoresis method. The
      vWF multimeric analysis showed that all multimers decreased to the same degree,
      corresponding to type-I vWS.

PMID- 8872133
TI  - Relationship between prothrombin activation fragment F1 + 2 and serum
      cholesterol.
AB  - Plasma levels of fibrinogen, factor VIIc and prothrombin fragment F1 + 2, a
      marker of thrombin generation in vivo, were studied in 68 subjects with serum
      total cholesterol (TC) levels between 135 and 349 mg/dl but without clinical
      evidence of cardiovascular disease and other atherosclerotic risk factors. F1 + 2
      plasma levels were directly correlated with TC (p < 0.0004), low-density
      lipoprotein cholesterol (LDL-C; p < 0.0018) and factor VIIc (p < 0.024). Thirty
      five subjects with TC greater than 249 mg/dl (median value of the whole group)
      showed higher levels of F1 + 2 (p < 0.0001) and fibrinogen (p < 0.0015) than
      those with TC lower than 249 mg/dl. In subjects with TC > 249 mg/dl and F1 + 2 >
      1.2 nM (median value of the whole group), a cholesterol-lowering drug
      (simvastatin) was able to reduce F1 + 2 (p < 0.009) as well as TC and LDL-C. This
      study shows a relationship between serum cholesterol and the rate of thrombin
      generation supporting the hypothesis that a hypercoagulable state may occur in
      hypercholesterolemic subjects before the onset of clinical evidence of
      atherosclerotic cardiovascular disease.

PMID- 8872134
TI  - Reexamination of the extent of the activation of Lys78 plasminogen by tissue
      plasminogen activator in the presence of polymerized fibrin.
AB  - The rate of the conversion of Lys78 plasminogen (Lys78-plg) to Lys78 plasmin by
      tissue plasminogen activator (tPA) was directly quantitated by SDS-PAGE. The
      apparent second-order rate constant (Kapp) was (0.27 +/- 0.07) x 10(3)/M/s for
      single-chain tPA and Lys78-plg, and was enhanced approximately 5-fold by
      fibrinogen and 17-fold by polymerized fibrin. Kapp was (1.57 +/- 0.46) x
      10(3)/M/s for two-chain tPA and Lys78-plg, and was enhanced approximately 2.6
      fold by fibrinogen and 3.6-fold by fibrin. The factor of the enhancement by
      polymerized fibrin was far less than in previous reports in which chromogenic
      substrate was commonly employed.

PMID- 8872135
TI  - Platelet-derived microparticles in alloxan-induced diabetes in rabbits.
AB  - To study platelet-derived microparticle generation in diabetes mellitus, we
      injected alloxan into male Japanese white rabbits. Injection of alloxan induced
      diabetes, but did not cause any significant change in various biochemical and
      hematological parameters. However, diabetic rabbits showed a significant
      elevation of platelet-derived microparticles from 8 weeks after alloxan injection
      (week 0: 0.45 +/- 0.24%; week 8: 1.12 +/- 0.61%, p < 0.005). These microparticles
      are known to have prothrombinase activity, suggesting that they may promote
      vascular complications in diabetes and may be used as a marker of vascular
      disease.

PMID- 8872136
TI  - Immunocytochemical demonstration of a new vimentin-associated protein in 3T3
      fibroblasts.
AB  - Using a xanthophore cytoskeletal preparation as immunogen, we have produced a
      monoclonal antibody, A2, which recognized a 160 kDa protein in 3T3 fibroblasts.
      This protein makes up a cytoplasmic filamentous system, which colocalizes with
      vimentin filaments. When microtubules and actin filaments are dissolved by high
      salt extraction, staining with antibody A2 is unaffected. Immunoblot analysis
      confirms that the 160 kDa protein is co-isolated with vimentin during in vivo
      high salt extraction. Following vinblastine treatment, both the 160 kDa protein
      and vimentin become localized to perinuclear caps, as do other intermediate
      filaments and their associated proteins; after vinblastine removal, the
      immunostaining produced by A2 becomes filamentous. Immunoelectron microscopy
      demonstrates that antibody A2 stains a filament system with a diameter of about
      10 nm. Our observations suggest that the 160 kDa protein may be a new vimentin
      associated protein which differs from the intermediate filament-associated
      proteins previously reported, and is widely distributed in several cell types.

PMID- 8872137
TI  - Androgen receptor in rat Harderian and submandibular glands.
AB  - Androgens regulate the development and sexual dimorphism of rodent Harderian and
      submandibular glands. This effect is believed to be mediated by the androgen
      receptor. Immunohistochemistry and immunoblotting were carried out to study the
      receptor in normal, castrated and dihydrotestosterone-supplemented rat Harderian
      and submandibular glands. Immunohistochemically, the most intense nuclear
      staining was observed in the acinar cells of the submandibular glands, followed
      by intercalated duct cells. The granular convoluted tubules showed weak
      immunostaining and the striated ducts were negative. In the Harderian gland,
      nuclear staining was seen in both type I and II secretory cells. Castration and
      treatment had no effect on the expression of the androgen receptor protein in
      either gland. A 110 K androgen receptor signal was detected by immunoblotting in
      the Harderian gland but not in the submandibular gland. An experiment was
      designed to explore the possible effect of proteinases on the receptor protein in
      the homogenate of submandibular gland. Our results demonstrate the cell-specific
      location of the receptor in Harderian and submandibular glands, and show that the
      expression of the receptor protein is androgen-independent.

PMID- 8872138
TI  - 5-Hydroxytryptamine immunoreactivity is detectable in sympathetic nerve fibres in
      rat oral tissues.
AB  - The aim of this investigation was to examine if 5-hydroxytryptamine (5-HT) is
      detectable not only in mast cells but also in sympathetic nerve fibres in oral
      sites of the rat, including the periodontal ligament, pulp, palatal mucosa, and
      vestibular sulcus. Antibodies against 5-HT and tyrosine hydroxylase were used.
      Maxillae from rats were dissected free, fixed, decalcified, cut transversally,
      and processed for immunohistochemistry. Nerve fibres showing 5-HT-like
      immunoreactivity were regularly observed in the walls of the arteries and
      arterioles in the vestibular sulcus and the periodontal ligament. However, 5-HT
      like immunoreactivity was not seen in the walls of the vessels of the palatal
      mucosa. Interestingly, 5-HT-like immunoreactivity coexisted with tyrosine
      hydroxylase-like immunoreactivity in the innervation of the periodontal ligament
      and the vestibular sulcus. Thus, the present study gives morphological correlate
      for the occurrence of effects of 5-HT derived not only from mast cells but also
      from sympathetic nerve fibres in oral tissues. The source of 5-HT in the nerve
      fibres as well as the functional implications of the observations remain to be
      determined.

PMID- 8872139
TI  - Interleukin-1 alpha induces variations of the intranuclear amount of
      phosphatidylinositol 4,5-bisphosphate and phospholipase C beta 1 in human
      osteosarcoma Saos-2 cells.
AB  - Some key elements of signal transduction have been identified within the nucleus
      and demonstrated to be responsive to specific agonists in numerous cell types. In
      particular, mitogenic stimuli have been reported to induce a transient increase
      of the nuclear phospholipase C beta 1 activity, causing the release of inositide
      derived second messengers, whereas differentiating stimuli induced a decrease of
      the enzyme activity and an increase of nuclear phosphatidylinositol 4,5
      bisphosphate (PIP2). Recently, we reported evidence, in human osteosarcoma Saos-2
      cell lines, on the presence of specific nuclear phospholipase C isoforms and on
      the activation of phospholipase C beta 1 in the nucleus following the exposure to
      interleukin-1 alpha. In this study we report immunocytochemical ultrastructural
      evidence on quantitative variations of PIP2 and phospholipase C beta 1 amounts in
      the nucleus of Saos-2 cells at different times of exposure to interleukin-1
      alpha. After short periods of culture in the presence of the agonist, the
      intranuclear amount of PIP2 is decreased, while a translocation of phospholipase
      C beta 1 occurs from the cytoplasm to the nucleus, in correspondence with the
      increased hydrolyzing activity of the enzyme. After longer periods of incubation
      with interleukin-1 alpha, on the other hand, the intranuclear amount of PIP2 is
      restored to initial level, while the amount of phospholipase C beta 1 is
      increased both at the nuclear and cytoplasmic level, when its activation is no
      longer effective. The results, compared with those obtained in other cell types
      responsive to given agonists, account for a cell-specific modulation of signal
      transduction based on polyphosphoinositide breakdown at the nuclear level.

PMID- 8872140
TI  - Peri- and postnatal changes in reduced nicotinamide adenine dinucleotide
      phosphate-cytochrome P-450 reductase content in hepatocytes of rats.
AB  - To study the process of the expression of reduced nicotinamide adenine
      dinucleotide phosphate-cytochrome P-450 reductase (EC 1.6.2.4) in the liver
      during development, the amount of enzyme in the cytoplasm of periportal and
      perivenular hepatocytes in sections cut from livers of male rats was measured
      during peri- and postnatal growth by quantitative immunohistochemistry with a
      video image processor. In livers of 19-day-old foetuses, the reductase content in
      the cytoplasm of periportal and perivenular hepatocytes was 0.16 microM and 0.20
      microM, respectively. From the 19th day of gestation to 5 days after birth, the
      enzyme content increased markedly in the cytoplasm of periportal (288%) and
      perivenular hepatocytes (301%). Subsequently, the content in the cytoplasm of
      periportal hepatocytes increased slightly (46%) from 5 to 20 days of age,
      remained unchanged from 20 to 45 days of age, and increased slightly (15%) from
      45 to 90 days of age. However, the content in the cytoplasm of perivenular
      hepatocytes increased progressively (125%) between 5 and 90 days of age. Thus,
      the amount of cytochrome P-450 reductase increases markedly in periportal and
      perivenular hepatocytes during the perinatal period, and subsequently the enzyme
      content increases gradually in periportal hepatocytes and progressively in
      perivenular hepatocytes. The present results also suggest that the divergence
      between cytochrome P-450 expression and the cytochrome P-450-dependent drug
      metabolic activity in hepatocytes during the perinatal period, found in previous
      studies, can be attributed to a low cytochrome P-450 reductase density in the
      membrane of endoplasmic reticulum of periportal and perivenular hepatocytes.

PMID- 8872141
TI  - Detyrosination of tubulin is not correlated to cold-adaptation of microtubules in
      cultured cells from the Atlantic cod (Gadus morhua).
AB  - Isolated cod brain microtubules from the cold-adapted Atlantic cod (Gadus morhua)
      have previously been shown to be highly detyrosinated, a post-translational
      modification of tubulin usually found in stable subsets of microtubules. In this
      study we found this was not restricted only to isolated brain microtubules.
      Microtubules in primary cultures of brain and skin cells were composed of both
      tyrosinated (Tyr)- and detyrosinated (Glu)-tubulin seen by immunocytochemistry.
      Immunoelectron microscopy of isolated microtubules showed that individual
      microtubules were composed of a mixture of Tyr- and Glu-tubulin. Leukocytes with
      extending lamellopodia contained only microtubules stained with the antibody
      against Tyr-tubulin, and isolated heart tubulin lacked both Tyr- and Glu-tubulin,
      suggesting that a relative high level of detyrosination is a characteristic of
      most, but not all, cod microtubules. Brain cell microtubules were more resistant
      to mitotic inhibitors than skin cell microtubules, but this was not correlated to
      a difference in detyrosination. Brain and skin cell microtubules were only
      partially disassembled when incubated at 0 degrees C. Upon reassembly of
      microtubules at 12 degrees C, microtubules were still made of mixtures of Tyr-
      and Glu-tubulin, indicating that detyrosination of assembled microtubules is
      rapid and/or that in cod cells in contrast to mammalian cells, Glu-tubulin can
      reassemble to microtubules. Our data show that most cod microtubules are highly
      detyrosinated, but this is not the cause of their cold adaptation or drug
      stability.

PMID- 8872142
TI  - A combined staining method for argyrophilic nucleolar organizer regions and for
      glial fibrillary acidic protein in astrocytes of human brain.
AB  - Different protocols are described for the combined staining method by which
      argyrophilic nucleolar organizer region sites can be evaluated in human
      astrocytes that are immunoreactive for glial fibrillary acidic protein. Among the
      four protocols studied, the following method was superior to others in terms of
      unambiguous visualization of the regions in glial fibrillary acidic protein
      positive astrocytes; the first step was immunostaining for the protein with a
      blue colour reaction of alkaline phosphatase, followed by sequential colloidal
      silver staining for the regions. By this double staining method, we have
      demonstrated that the reactive astrocytes found in white matter around the
      metastatic lesion of carcinoma and the infarction, contain more argyrophilic
      nucleolar organizer regions in terms of the count as well as the area than glial
      fibrillary acidic protein-positive astrocytes present in the white matter of the
      normal brain. In conclusion, the double staining may provide valuable information
      on the cellular activity of astroglia when performed on routine formalin-fixed
      paraffin sections of the human brain.

PMID- 8872143
TI  - Microscopic, lymphocytic and collagenous colitis.

PMID- 8872144
TI  - Gastrointestinal autonomic nerve tumours: a report of nine cases.
AB  - We describe the clinicopathological features of gastrointestinal autonomic nerve
      tumours in nine patients where the diagnosis was confirmed by electronmicroscopy.
      Most patients presented with abdominal pain. At laparotomy, large intra-abdominal
      tumour masses were found which tended to be cystic and haemorrhagic. The
      predominant histological patterns were nests, sheets and fascicles of spindle and
      epithelioid cells. Immunohistochemistry showed positive staining for neuron
      specific enolase (9/9), PGP 9.5 (9/9), NKI/C3 (7/9), vimentin (7/9), alpha-smooth
      muscle actin (5/9), vasoactive intestinal peptide (3/9) and CD34/QBend10 (2/9).
      Grimelius staining was positive in two of nine cases. All tumours were negative
      for CAM 5.2, chromogranin, synaptophysin, Leu 7, neurofilament protein, muscle
      specific actin (HHF-35) and desmin (D33). Ultrastructural examination showed
      cellular processes and dense-core granules in all cases. Three tumours had
      microtubules and/or intermediate filaments, particularly in cell processes.
      Skeinoid fibres were seen in three cases. No convincing synapses or small
      (synaptic-type) vesicles were identified. There was no evidence of epithelial,
      smooth muscle or nerve sheath differentiation. Two patients died due to tumour,
      two died of unknown causes and the remainder are alive 2-44 months after
      presentation. Four of the five survivors have recurrent/residual intra-abdominal
      tumour. So-called gastrointestinal autonomic nerve tumours are apparently slow
      growing malignant tumours showing neuronal differentiation. Four cases arose in
      the mesentery/retroperitoneum or omentum rather than bowel wall and therefore a
      more appropriate nomenclature might be intra-abdominal stromal tumour with
      neuronal differentiation.

PMID- 8872145
TI  - Apoptosis and proliferation in gastric carcinoma: the association with
      histological type.
AB  - We examined apoptosis in 33 gastric carcinomas using the terminal
      deoxynucleotydil transferase mediated dUTP-digoxigenin nick end labelling
      technique (TUNEL). Of the tumours, nine were well-differentiated, 13 moderately
      differentiated and 11 poorly differentiated. In addition, we also analysed MIB-1,
      a cell proliferation antigen. Morphologically, apoptotic tumour cells were more
      frequently observed in well-differentiated tumours. In addition, apoptotic
      signals of the TUNEL method were seen even in the nuclei of tumour cells which
      did not show apoptosis. The nick end labelling index was 51.0 +/- 26.3 in the
      well-differentiated and moderately differentiated tumours and 28.0 +/- 18.8 in
      poorly differentiated tumours. The mean of apoptotic body index and nick end
      labelling index were both significantly higher in well-differentiated and
      moderately differentiated tumours than in the poorly differentiated type (P <
      0.0001, P = 0.008). The MIB-1 labelling index and higher in poorly differentiated
      tumours than in the well-differentiated or moderately differentiated tumours, and
      labelled cells were more numerous in the superficial region than in the middle
      and deep regions of tumours. No apparent correlation was found between the nick
      end labelling index and the MIB-1 labelling index. The high number of apoptotic
      cells (the high Nick end labelling index) and low proliferation potentiality (the
      low MIB-1 labelling index) in well-differentiated gastric carcinomas may thus be
      related to their natural tendency to demonstrate slow growth.

PMID- 8872146
TI  - Expression of cytokeratins typical for ductal and squamous differentiation in the
      human stomach: an immunohistochemical study of normal foveolar epithelium,
      Helicobacter pylori gastritis and intestinal metaplasia.
AB  - The expression of the cytokeratins (CK) 1, 5, 6, 7, 10, 13 and 14 was studied
      immunohistochemically in gastric biopsies from both the antrum and the body of 70
      patients. Normal gastric foveolar epithelium (9 cases) Helicobacter pylori
      gastritis (23) and intestinal metaplasia (38) were examined. Positive staining
      results for CK 1, 5, 10 and 14 were not observed using the 34 beta E12 antibody.
      With antibodies to CK 5/6, 7 and 13 some, but not all cases, were immunoreactive.
      Predominantly positive staining included less than 10% of the cells and was
      always restricted to the tips and the juxtaluminal areas of the foveolae. No
      difference was seen between the antrum and the body. Comparing normal gastric
      mucosa with gastritis and intestinal metaplasia, cases positive for CK 5/6 were
      observed less frequently in intestinal metaplasia types II and II compared to the
      other groups. CK 7 was expressed exclusively in intestinal metaplasia. CK 13 was
      seen in all groups of specimens. Thus, cytokeratins typical for ductal structures
      (CK 7) and squamous epithelia (CK 5/6, CK 13) can be regarded as an inconstant,
      but not unusual observation in the gastric mucosa. Their expression may be
      controlled by both differentiation-related as well as environmental factors.

PMID- 8872147
TI  - Expression of beta-catenin in normal breast tissue and breast carcinoma: a
      comparative study with epithelial cadherin and alpha-catenin.
AB  - Expression of beta-catenin was investigated in normal breast tissue and 66 breast
      carcinomas in conjunction with expression of epithelial cadherin (E-CD) and alpha
      catenin. In normal mammary ducts and acini, intense beta-catenin immunoreactivity
      was present at the basolateral surfaces of luminal epithelium and weak
      immunoreactivity was observed at the lateral borders of myoepithelial cells. No
      beta-catenin was revealed at the myoepithelial basal surface. The intercellular
      expression of beta-catenin, as well as of E-CD and alpha-catenin, was also
      observed in carcinoma tissues with varying staining intensity. Almost all of 10
      intraductal carcinomas and approximately 70% of 41 invasive ductal carcinomas
      expressed the three molecules at the same level as in normal glands, whereas
      approximately 80% of 13 invasive lobular carcinomas showed severe deficiency of
      them. Two lobular carcinomas in situ showed complete absence of all of the
      proteins. Some of these findings were confirmed biochemically by immunoblotting
      analysis. In invasive ductal carcinomas, alpha-catenin was reduced more
      frequently in diffuse than in solid type tumours, whereas the level of expression
      of beta-catenin and E-CD was unchanged between them. No correlation was present
      between reduced expression of the adhesion molecules and lymph node metastasis.

PMID- 8872148
TI  - MIB-1 immunoreactivity reveals different labelling in low-grade and in malignant
      epithelial neoplasms of the choroid plexus.
AB  - MIB-1 immunohistochemistry was carried out on a retrospective biopsy series of
      epithelial choroid plexus neoplasms in order to assess the proliferation rate of
      tumour cells. The material included 14 cases of papilloma (WHO grade I) and five
      cases of carcinoma (WHO grade III). There was one recurrent tumour in the
      papilloma group, while three patients with carcinoma experienced recurrence.
      Choroid plexus obtained at autopsy from paediatric and adult patients with
      unrelated diseases served as control. The average MIB-1 labelling index of
      choroid plexus papillomas was 3.7%, while that of carcinomas was 14%, and that of
      normal choroid plexus was 0.02% to 0.06%. The age and sex of the patients as well
      as the tumour localization were not found to influence MIB-1 reactivity. The
      labelling index of recurrent lesions was not significantly different from that of
      the corresponding primary tumours. High MIB-1 labelling indices were associated
      with less favourable post-operative outcome in choroid plexus carcinomas and in
      one papilloma with atypical histology. However, most tumours with atypical
      histological features did not exhibit distinctive MIB-1 labelling indices.
      Analysis of growth fraction by MIB-1 immunohistochemistry may prove a useful
      ancillary method for assessing the malignant potential of choroid plexus
      neoplasms.

PMID- 8872149
TI  - Thrombomodulin as a marker of vascular and lymphatic tumours.
AB  - The aim of this study was to evaluate the utility of a new commercially available
      antibody to thrombomodulin as an endothelial marker in formalin-fixed paraffin
      embedded tissue. The expression of thrombomodulin in a variety of 50 vascular and
      lymphatic neoplasms and malformations was compared to the expression of von
      Willebrand factor, QBend 10 (CD34) and JC70 (CD31). We showed that thrombomodulin
      was the best marker of lymphatic endothelium and also stained a higher percentage
      of malignant vasoformative tumours when compared to the other markers. We
      recommend the assessment of thrombomodulin expression in the differential
      diagnosis of malignant vasoformative neoplasms and in the detection of lymphatic
      endothelium for evidence of tumour permeation.

PMID- 8872150
TI  - The immunoexpression of bcl-2 and p53 in Kaposi's sarcoma.
AB  - The aim of this study was to examine the immunohistochemical expression of p53
      and bcl-2 in Kaposi's sarcoma and relate this with proliferation index (as
      measured by MIB-1 staining) and clinicopathological subtypes. Twenty formalin
      fixed, paraffin-embedded cases of Kaposi's sarcoma were stained with commercially
      available antibodies to p53, bcl-2 and MIB-1, after pressure cooking antigen
      retrieval. All cases were strongly positive for bcl-2 with the majority
      containing more than 75% positive cells. In comparison, p53 expression was less
      striking. Eleven cases contained less than 24% (+1) of cells staining positively.
      Only two cases showed greater than 75% of positive cells, and both of these
      latter two lesions had metastasized. The MIB-1 staining in all cases of Kaposi's
      sarcoma was strongly positive, irrespective of clinicopathological type, in
      keeping with the highly proliferative nature of this lesion. Thus, we have
      demonstrated uniformly increased expression of bcl-2 protein in Kaposi's sarcoma
      irrespective of clinicopathological subtype and MIB-1 staining, while p53
      expression is relatively less common, except in those cases which have
      metastasized. This may help identify those cases that will behave in a more
      aggressive manner. However, more cases need to be evaluated to verify this.

PMID- 8872151
TI  - Parotid involvement by desmoplastic melanoma.
AB  - Desmoplastic malignant melanoma often arises in sun damaged skin of the head and
      neck and shows frequent neurotropism. Although metastatic melanoma frequently
      involve the parotid, direct spread to the parotid has been rarely reported. We
      evaluated five cases of desmoplastic malignant melanoma involving the parotid
      gland with clinical and pathological evidence of precursor cutaneous lesions in
      four of the five cases. The parotid involvement in four cases was tumoural, and
      three of these were not clinically suspected to be melanoma. The histological
      appearance in all five cases was that of a sarcomatoid tumour.
      Immunohistochemistry and electronmicroscopy performed on three of the cases
      showed only evidence of schwannian differentiation: the tumour cells were
      positive for S-100 protein and vimentin, and negative for cytokeratin and HMB-45.
      Electronmicroscopy showed no evidence of melanogenesis. All five tumours showed
      histological evidence of prominent neurotropism with one case demonstrating
      extension from overlying skin along cutaneous nerves to the superficial parotid.
      Thus, desmoplastic malignant melanoma may involve the parotid by neurotropic
      spread and can be pathologically indistinguishable from malignant schwannoma, a
      diagnosis which may be made erroneously in the absence of clinical information.

PMID- 8872152
TI  - Peroxisome proliferation associated with fibrinogen storage in the liver.
AB  - We report a patient with fibrinogen storage disease in which there was
      proliferation of normal-sized peroxisomes in the hepatocytes. this phenomenon has
      previously been described in several acquired liver diseases. We believe that
      this is an adaptation response due to decreased microsomal isoenzyme activity as
      a result of the excess accumulation of fibrinogen in the endoplasmic reticulum.

PMID- 8872153
TI  - Gastrointestinal stromal tumour with skeinoid fibres and bidirectional
      immunohistochemical differentiation.

PMID- 8872154
TI  - Carotid body paraganglioma in von Hippel-Lindau disease: a rare association.

PMID- 8872155
TI  - Dermatomyofibroma: further support of its myofibroblastic nature by
      electronmicroscopy.

PMID- 8872156
TI  - Pericardial myolipoma: a tumour presenting as a mediastinal mass and containing
      oestrogen receptors.

PMID- 8872157
TI  - Dermoid cyst of the caecum.

PMID- 8872158
TI  - Malignant transformation in a schwannoma.

PMID- 8872159
TI  - Follicular lymphomas.

PMID- 8872160
TI  - Parotid MALT lymphoma in an HIV positive child.

PMID- 8872161
TI  - Structure and content of the major histocompatibility complex (MHC) class I
      regions of the great anthropoid apes.
AB  - The origins of the functional class I genes predated human speciation, a
      phenomenon known as trans-speciation. The retention of class Ia orthologues
      within the great apes, however, has not been paralleled by studies designed to
      examine the pseudogene content, organization, and structure of their class I
      regions. Therefore, we have begun the systematic characterization of the Old
      World primate MHCs. The numbers and sizes of fragments harboring class I
      sequences were similar among the chimpanzee, gorilla, and human genomes tested.
      Both of the gorillas included in our study possessed genomic fragments carrying
      orthologues of the recently evolved HLA-H pseudogene identical to those found in
      the human. The overall megabase restriction fragment patterns of humans and
      chimpanzees appeared slightly more similar to each other, although the HLA-A
      subregional megabase variants may have been generated following the emergence of
      Homo sapiens. Based on the results of this initial study, it is difficult to
      generate a firm species tree and to determine human's closest evolutionary
      neighbor. Nevertheless, an analysis of MHC subregional similarities and
      differences in the hominoid apes may ultimately aid in localizing and identifying
      MHC haplotype-associated disease genes such as idiopathic hemochromatosis.

PMID- 8872162
TI  - Allelic variants of human TCR BV17S1 defined by restriction fragment length
      polymorphism, single strand conformation polymorphism, and amplification
      refractory mutation system analyses.
AB  - Several human TCR BV gene subfamilies, including BV3, BV14, and BV17S1, are
      single member genes but are overutilized among activated CD4+ synovial T cells in
      the rheumatoid arthritis (RA). To define the role of these TCR BV genes in the
      pathogenesis of disease, it is critical to characterize the genomic organization
      and the allelic variations of these genes. In this study we describe allelic
      variations of BV17S1 defined by restriction fragment length polymorphism (RFLP),
      single strand conformation polymorphism (SSCP), and amplification refractory
      mutation system (ARMS) analyses. A single nucleotide replacement (C/T) results in
      an amino acid substitution (F/L) in the leader and distinguishes BV17S1*1 from
      BV17S1*2. This nucleotide substitution was found to create a BsmAI restriction
      enzyme recognition site in BV17S1*2. Therefore genotypic analyses can be
      performed either by the SSCP or RFLP method. The analyses of 75 unrelated
      individuals show that the frequency for allele BV17S1*1 is 52.7% and for allele
      BV17S1*2 is 47.3%. Both alleles are functionally expressed and are distributed
      within CD4+/CD8+ T cell subsets. Another point mutation in the CDR2 region of
      BV17S1, which results in the amino acid replacement of Gln by His, originally
      identified form a cDNA clone, has now been confirmed as an allele by ARMS
      analysis using genomic DNA preparations and designated to as BV17S1*3. Screening
      of this CDR2 related variant among normal populations indicates that this is a
      rare allele (1 of 75). Although this variant may be of functional significance,
      the genotypic analysis and functional studies are difficult due to the low
      frequency of BV17S1*3. In an attempt to define a correlation between BV17S1
      allelic usage and susceptibility to RA, the germline distribution of BV17S1
      alleles *1 and *2 has been examined in a small number of RA patients and no
      skewed usage has been identified.

PMID- 8872163
TI  - The impact of DR3 microvariation on peptide binding: the combinations of specific
      DR beta residues critical to binding differ for different peptides.
AB  - HLA-DR molecules are a group of highly polymorphic glycoprotein heterodimers that
      present peptide antigens to T lymphocytes for immune surveillance. To assess the
      significance of limited polymorphism on the functional differentiation of DR
      molecules, the binding of several immunogenic peptides to the DR3 microvariants
      [DR(alpha, beta 1*0302) and DR(alpha, beta 1*0301)] and to mutants of these DR3
      molecules was examined. This analysis has shown that each residue (DR beta 26, DR
      beta 28, DR beta 47, and DR beta 86), which differentiates these two DR3
      molecules, contributes to their functional distinction and that the relative
      contribution of each residue varies for different peptide/DR3 complexes. For
      example, DR beta 28 and DR beta 86 controlled the mycobacterium tuberculosis 65
      kD heat shock protein peptides 3-13 and 4-15 (HSP) binding specificity to DR
      (alpha, beta 1*0301). [HSP does not bind to DR(alpha, beta 1*0302)], whereas DR
      beta 26, DR beta 28, and DR beta 86 controlled the influenza hemagglutinin
      peptide 306-318 (HA) binding specificity to DR(alpha, beta 1*0302). [HA does not
      bind to DR(alpha, beta 1*0301).] In comparison, DR beta 86 alone controlled the
      binding level difference of sperm whale myoglobin peptide 132-151 (SWM) and of
      myelin basic protein peptide 152-170 (MBP) [both bind to DR(alpha, beta 1*0301)
      at levels five times greater than to DR(alpha, beta 1*0302)] to the DR3
      molecules. Although not critical, additional DR beta residues influenced the
      binding level of individual peptides of each of the DR3 molecules and, again, the
      combinations of these residues differed for different peptide/DR3 complexes.
      These data showed that individual DR residues vary in their relative contribution
      to the interaction between a specific DR molecule and different peptides and that
      limited polymorphism can create substantial differences in the peptide binding
      profiles among DR molecules.

PMID- 8872164
TI  - The in vitro response to human fibroblast-derived extracellular matrix proteins
      is restricted by specific HLA class II genes. Relevance for coeliac disease.
AB  - Coeliac disease is an immunologic disease of the small intestine which is caused
      by ingestion of wheat gliadin, the disease-promoting agent. The disease
      associates strongly with the particular HLA type, HLA-DQA1*0501, DQB1*0201
      alleles. Further specific autoantibodies against reticulin and endomysium are
      found in patients; these autoantibodies appear to be disease specific. An
      extracellular matrix noncollagenous protein reacts specifically with CD patients'
      serum immunoglobulin A and is the target of antireticulin antibodies. In this
      study the immune response to this matrix protein was analyzed in vitro in normal,
      healthy individuals. Our study shows that the immune response to Fb-CDAP is
      strictly regulated by the HLA-DR3, DQA1*0501, DQB1*0201 alleles, and that only
      those cells which were positive for these alleles produced an immune response. On
      the other hand, half of the cells positive for these HLA alleles were responders.
      Monoclonal antibodies to DR and DQ inhibited the response in an additive way,
      showing that both DR and DQ can act as an antigen-presenting structure. The
      immune response to gliadin has been shown to associate with the same HLA type as
      CD, but the association is not as strong. Our results show that the immune
      responses to Fb-CDAP can be generated in vitro in genetically predisposed persons
      in the absence of CD.

PMID- 8872165
TI  - Human CD4-reactive antibodies from SLE patients induce reversible inhibition of
      polyclonal T lymphocyte proliferation.
AB  - We report on isolation of human polyclonal CD4-reactive antibodies of IgM and/or
      IgG isotypes from several SLE patients. These antibodies bound specifically to
      CD4-expressing cell lines and to rCD4 in ELISA and immunoblots. Saturation of CD4
      binding sites occurred at antibody concentrations between 5 and 15 micrograms/ml.
      Anti-CD4 antibodies, in a dose-dependent manner, suppressed the proliferative
      responses of human peripheral blood mononuclear cells (PBMC) to superantigens
      (Staphylococcal enterotoxins A and B), anti-CD3 antibodies, and mitogens (PWM and
      Con A, but not PHA). They could also inhibit the proliferation of highly purified
      human T cells induced by immobilized anti-CD3 antibodies. To promote their
      effects on T cells, human anti-CD4 antibodies had to be present at lymphocyte
      cultures before or at the time of priming. There was no significant inhibition
      when antibodies were added more than 24 h following T cell activation.
      Substantial evidence that the immunosuppression induced by anti-CD4 antibodies
      was due to their direct effect on T cells was obtained. Down-regulatory effect of
      anti-CD4 antibodies could be significantly reversed by addition of exogenous IL-2
      and by preincubation with soluble recombinant (r)CD4. Interestingly, at least one
      affinity-purified anti-CD4 antibody could costimulate the T cell proliferation
      induced by superantigens or anti-CD3 antibodies, especially when used at
      subsaturating concentrations (1-4 micrograms/ml) and when added subsequently to
      the initiation of cultures.

PMID- 8872166
TI  - Diverse usage of human T-cell receptor gene segments in HLA-DR1 allospecific T
      cell clones.
AB  - T-cell recognition of alloantigen involves both the MHC molecule and its
      associated peptide ligand. To understand the relationship between the specificity
      of alloantigen recognition and the structure of TCR molecules, we have
      investigated TCR gene utilization by sequencing TCR genes from well-defined
      allospecific T-lymphocyte clones. Alloreactive TLC consisted of a panel of clones
      primed to recognize DR1-related alloantigens. Our sequencing results revealed
      extensively diverse, but nonrandom, usage of TCR AV and BV gene segments and
      essentially no conservation in CDR3 or junctional sequences. Such observations
      are consistent with allospecific TCR that interact with MHC molecules on a
      generic level while recognizing specific peptides. They also reduce potential
      enthusiasm for anti-TCR therapy in allograft rejection.

PMID- 8872167
TI  - Activation status of T and NK cells in the endometrium throughout menstrual cycle
      and normal and abnormal early pregnancy.
AB  - Endometrial lymphocytes were studied at all stages throughout the menstrual cycle
      and early pregnancy by flow cytometry to examine different lymphocyte
      subpopulations and the expression of the T- and NK-cell activation markers. After
      pregnancy, CD8+CD3+ lymphocytes were decreased in the decidua. In both
      endometrium and decidua, more T cells expressed CD69, CD71, HLA-DR, and CD38
      antigens than in peripheral blood. After pregnancy, CD71+CD3+ lymphocytes were
      further increased. CD25+CD3+ lymphocytes decreased significantly in the
      endometrium and decidua of ectopic pregnancies, but not in the decidua of normal
      pregnancies. These findings indicate that T cells are regionally activated in the
      first trimester, and it may be the result of the stimulation by fetal antigens.
      NK cells were the most abundant cell type in the decidua, which expressed the
      phenotype CD16- CD56+, and CD57-CD56+. The proportion of activated decidual NK
      cells was increased in anembryonic pregnancies more than in normal pregnancies,
      although the total NK subpopulation was similar in both groups. This might result
      in increased NK cytotoxicity in anembryonic pregnancies. In conclusion, T cells
      are activated, but NK cytotoxicity is decreased in the decidua of early normal
      pregnancies. This might be important in the control of trophoblast growth and
      placental development.

PMID- 8872168
TI  - Distribution of HLA class II alleles and haplotypes in insulin-dependent Moroccan
      diabetics.
AB  - HLA class II polymorphism in Moroccan IDDM patients has not been investigated so
      far. In this study, HLA-DRB1, -DQA1, and -DQB1 allele and haplotype frequencies
      were analyzed in 125 unrelated Moroccan IDDM patients and 93 unrelated healthy
      controls, all originating from the Souss region and mostly of Berber origin. Some
      common features with other Caucasian groups were observed, in particular, a
      predisposing effect of the DRB1*03-DQA1*0501-DQB1*0201 and DRB1*04-DQA1*0301
      DQB1*0302 alleles or allelic combinations. The Moroccan IDDM group also presented
      with more specific characteristics. Among DRB1*04 subtypes, DRB1*0405 was
      associated with susceptibility to and DRB1*0406 with protection from the disease.
      The haplotype and the relative predispositional effect (RPE) analyses indicated
      that the DRB1*08-DQA1*0401-DQB1*0402 haplotype was also associated with
      susceptibility to IDDM. Interestingly, the DRB1*09-DQA1*0301-DQB1*0201 haplotype,
      completely absent from the control group and very rare in North African
      populations, was observed in 7.2% of the Moroccan diabetics. Conversely, the
      DRB1*07-DQA1*0201-DQB1*0201 and DRB1*15-DQA1*0102-DQB1*0602 haplotypes were
      associated with protection from IDDM. Finally, we observed an age-dependent
      genetic heterogeneity of IDDM, the frequencies of predisposing alleles being
      higher and those of protective alleles lower in childhood- than in adult-onset
      diabetics. Our data on Moroccan diabetics, together with data on European and
      Northern Mediterranean patients, suggest a gradient of various HLA class II
      predisposing and protective markers that link these populations.

PMID- 8872169
TI  - Analysis of HLA-DM polymorphisms in sarcoidosis.
AB  - Sarcoidosis is a multisystemic granulomatous disorder showing significant
      increases in the HLA-DRB1*11, *12, *14 and *08 alleles in the Japanese
      population. To evaluate the role of polymorphism in the DMA and DMB genes in
      predisposition to sarcoidosis, seventy Japanese patients with sarcoidosis and 95
      unrelated healthy controls were analyzed in the third exon polymorphisms within
      the DMA and DMB genes by the PCR-RFLP method. There were no differences in the
      distribution of DMA alleles between the patient and control groups. The frequency
      of DMB*0102 was higher (p < 0.05) and that of DMB*0101 was lower (p < 0.05) in
      the patients than in the healthy controls. However, this association and negative
      association could be explained by linkage disequilibrium with the disease
      associated DRB1 alleles. The DMA and DMB genes do not primarily confer the
      susceptibility to sarcoidosis.

PMID- 8872170
TI  - Effect of major histocompatibility complex matching on the development of
      tolerance to primarily vascularized renal allografts: a study in miniature swine.
AB  - Prevention of rejection and the induction of transplantation tolerance are two
      related but separable phenomena that must both be considered in the analysis of
      the response to a transplanted organ. It is frequently hard to separate these
      phenomena in assessing the outcome of clinical transplants, because patients are
      rarely studied in the absence of immunosuppressive agents. Use of our partially
      inbred miniature swine has permitted us to examine the effects of selective MHC
      matching on transplant survival, and the data indicate that matching has an
      effect on both phenomena. Prevention of early rejection with CyA was possible for
      all mismatches examined, although it was clearly more difficult with increasing
      degrees of mismatching. On the other hand, tolerance induction after cessation of
      the immunosuppressive agent was dependent on presence of at least one matched MHC
      locus between the donor and recipient, with complete class II matching appearing
      to be the most successful way of assuring long-term graft survival. It is also
      apparent from our data that although durable tolerance to primarily vascularized
      renal allografts could be induced across a variety of selective MHC disparities,
      all cases involving a class II mismatch (ie, selective class I matched or one
      haplotype full MHC mismatched kidney allografts) underwent spontaneously
      reversible rejection crises during the early follow-up period. Such a clinical
      course might be unacceptable for human clinical trials, even though the transient
      renal dysfunction may reflect events involved in tolerance induction rather than
      true rejection (Gianello et al: Immunol Rev 133:19, 1993.). Indeed, we do not yet
      know whether or not further immunosuppressive treatment at the times of such
      crises may prevent rather than facilitate the induction of tolerance. On the
      other hand, in the case of selective two-haplotype class I mismatch the regimen
      utilized was capable of inducing tolerance to renal allografts in 100% of the
      recipients with minimal or no renal dysfunction throughout the follow-up period.
      Although the excellent results achieved with current antirejection agents has led
      to debate about the wisdom of HLA matching for cadaver transplants in terms of
      preventing rejection, our data would suggest that such matching might be of even
      greater importance for success of protocols in which attempts are made to induce
      transplantation tolerance. Because class II antigens are less polymorphic than
      are class I antigens, mismatching for class I antigens may be achievable for
      cadaver donor transplantation, and may provide the first situation in which these
      principles can be applied to clinical trials.

PMID- 8872171
TI  - Tumor necrosis factor (TNF) microsatellite haplotypes in relation to extended
      haplotypes, susceptibility to diseases associated with the major
      histocompatibility complex and TNF secretion.
AB  - TNFabc microsatellite haplotypes were determined on normal, type I diabetes and
      multiple sclerosis Caucasian MHC haplotypes in family studies. Although
      independent examples of conserved extended haplotypes usually had the same TNFabc
      haplotypes, there were a number of exceptions, suggesting that these loci are
      more mutable than most loci in the human MHC. Some TNFabc haplotypes were
      characteristic of only one extended haplotype, whereas others were shared by
      several different extended haplotypes. From the analysis of TNFabc on extended
      haplotype fragments, and assuming that the fragments arose by ancient homologous
      crossing over, it was possible to "map" TNF and how that it was somewhat closer
      to HLA-B than the complement region, corresponding to the physical map of this
      region. TNF haplotype associations with type I diabetes and multiple sclerosis
      were attributable to the known extended haplotype associations of these diseases.
      There was also a trend for higher TNF-alpha secretion by peripheral blood
      mononuclear cells from individuals homozygous for [HLA-B8, SC01, DR3] than from
      individuals homozygous for [HLA-B7, SC31, DR2].

PMID- 8872172
TI  - Restricted T-cell antigen receptor repertoire in bronchoalveolar T cells from
      normal humans.
AB  - The repertoire of variable alpha (AV) and beta (BV) TCR genes was compared in the
      peripheral blood and BAL fluid of five healthy individuals. Rearranged TCR
      transcripts were amplified by a reverse transcription-polymerase chain reaction,
      using oligonucleotide primers specific for 22 AV and 24 BV gene families. Nearly
      all AV and BV gene families were expressed in BAL T cells at levels similar to
      those in blood T cells. The diversity of AV and BV gene repertoire was examined
      further, testing the distribution of nucleotide lengths of TCR junctional
      regions. Most V gene families had a normal distribution of junctional region
      lengths in both blood and BAL T cells. Some gene families, particularly AV21 and
      BV9 in BAL samples, had a skewed banding pattern, with fewer bands or
      predominance of several bands. The limited diversity in TCR junctional region
      lengths was more prominent in CD8+ T cells from BAL fluids than from blood. CD4+
      T cells also contributed to the limited diversity in BAL T cells. The oligoclonal
      expansion of bronchoalveolar CD8+ T cells was confirmed by sequence analysis of
      AV21-constant alpha (AC) and BV9-BC junctional regions in the blood and BAL
      cells. The levels of V gene expression and the diversity of junctional region
      lengths were very similar in T cells obtained from three separate lobes of one
      donor. In general, skewed patterns of TCR junctional region lengths were not
      consistent over time two donors, over periods of 3 and 17 months. Together, these
      data show that the T-cell repertoire is diverse within the lungs of normal
      humans, except for an oligoclonal predominance of a few V gene families in both
      CD4+ and CD8+ T cells. The T-cell repertoire in the lungs changes over time,
      which may reflect environmental exposures.

PMID- 8872173
TI  - Primary alloreactive cytotoxic T-lymphocytes are not commonly restricted by self
      HLA class I antigens.
AB  - To assess the role of HLA Class I molecules in the indirect presentation of
      alloantigen, we have investigated the fine specificity and MHC restriction of in
      vitro primary alloreactive cytotoxic T-lymphocytes (CTL), using limiting dilution
      analysis of CTL precursor frequencies in HLA-mismatched responder-stimulator
      pairs. By employing split-well analysis of limiting dilution (LD) microcultures
      and third-party target cells bearing a stimulatory HLA Class I antigen alone or
      in combination with a single responder HLA antigen, we demonstrate that self
      Class I restriction of HLA-A- or HLA-B-specific CTL precursors is not a common
      feature of the primary in vitro alloresponse. Higher frequencies of alloantigen
      specific CTL precursors in the presence of self-HLA antigens were only detected
      in 5 of 31 limiting dilution assays established from seven different responder
      stimulator pairs. In two cases, the higher precursor frequencies could be
      explained on the basis of Class II-restricted presentation of Class I-derived
      antigenic peptide and are supported by flow cytometric analysis of HLA antigen
      expression on target cells. The remaining 3 assays of this type were suggestive
      of Class I restriction but revealed only marginally higher frequency estimates.
      All other LD assays revealed lower CTL precursor frequency estimates in the
      presence of self-HLA Class I antigens. A higher antigen-specific CTLp frequency
      was not detected when targets shared three HLA Class I antigens with the
      responder, demonstrating that we had not biased the responses by selecting single
      HLA antigen-sharing targets in the other assays. Analysis of reactivity against
      PHA blast targets at the single cell per well level demonstrated that CTL
      reactive only with the original stimulator comprised the majority of lytic
      reactions. Heteroclitic CTL (i.e., CTL that recognize single HLA targets only and
      not the original stimulator) formed only a small fraction of total reactivity.
      Our results confirm the role of Class II antigens in the indirect presentation of
      alloantigen in vitro but suggest that HLA Class I antigens play a limited role in
      this phenomenon.

PMID- 8872174
TI  - HLA-C genotyping of patient with Behcet's disease in the Japanese population.
AB  - Behcet's disease has been known to be strongly associated with a particular HLA-B
      allele, B51. To address the possibility that the HLA-C gene, which is closely
      linked to HLA-B but has been poorly defined for allo-antigen specificity by the
      serologic method is involved in the susceptibility to Behcet's disease, HLA-C
      genotyping was performed for 90 Japanese Behcet's disease patients by the PCR-SSP
      method. The frequencies of HLA-Cw*14 and -Cw*15 were significantly higher in the
      patient with Behcet's disease as compared to the controls (48.9% vs. 24.0%, p =
      0.0005, and 17.8% vs. 7.3%, p = 0.0434, respectively). On the other hand, the
      frequencies of HLA-Cw*0304 and -Cw*01 were significantly decreased in the patient
      group as compared to the control group (7.8% vs. 25.0%, p = 0.0027, and 23.3% vs.
      37.5%, p = 0.0398, respectively). The significantly higher HLA-Cw*14 and -Cw*15
      alleles may tightly correlate with the B51 antigen, and hence may have increased
      as a result of a linkage disequilibrium with B51. Accordingly, the HLA-C allele
      frequencies were compared for the B51-positive or -negative patients and
      controls, but there was no HLA-C allele showing a significant difference between
      these patient and control groups. Conversely, analysis of the HLA-B allelic
      distribution in association with HLA-Cw*14 revealed that in the healthy controls,
      B44 and B51 were present at the frequencies of 57.1% and 35.7% of the HLC-Cw*14
      positive individuals, respectively. In contrast, in the Cw*14-positive patients
      the frequency of B44 was merely 14.0% (p = 0.0001) and that of B51 was
      significantly high, amounting to 82.0% (p = 0.0001). These facts suggest that the
      pathogenic gene of Behcet's disease is not the HLA-C gene (HLA-Cw*14 and/or HLA
      Cw*15) but the HLA-B gene (HLA-B51) itself or a non-HLA gene residing in the
      centromeric side of the HLA-B gene rather than in the telomeric side around the
      HLA-C gene. This finding supports our previous mapping result, which located the
      susceptible gene between the TNF and HLA-B genes.

PMID- 8872175
TI  - Human leukocyte antigen-DRB1*1502 (DR2Dw12) transgene reduces incidence and
      severity of arthritis in mice.
AB  - A strong correlation exists between susceptibility to RA in humans and some DRB1
      alleles of the MHC region, such as DRB1*0401 and DRB1*0101. Meanwhile, incidences
      of other DR specificities, such as DR2, DR5, or DR7 have often been found reduced
      among RA patients. Like RA, susceptibility to mouse CIA is influenced by the MHC
      class II loci. To analyze the effect of a DRB1 molecule associated with low
      incidence of RA on mouse CIA, a human DRB1*1502 (DR2Dw12) transgene was
      introduced into CIA-susceptible B10.RQB3 (H2Aq) mice. Transgene-positive
      DRB1*1502 mice showed a significant reduction in the incidence and severity of
      arthritis. Moreover, the clinical reduction of arthritis correlated with the T
      cell proliferative response of B10.RQB3-DRB1*1502 mice against a self-derived
      DRB1 peptide from the third hypervariable region. Our results suggest that the
      DRB1*1502-mediated protection against CIA can be explained by the DRB1 molecule
      acting as a source of self-antigenic peptide which interferes with the T-cell
      response against immunodominant regions(s) of the arthritogenic type II collagen
      molecule. By analogy, a similar mechanism might play a critical role in
      influencing the class II-associated predisposition to RA.

PMID- 8872176
TI  - Binding of ALA-substituted analogs of HA306-320 to DR1101, DR1301, and DR0402
      molecules: correlation of DR-peptide interactions with recognition by a single
      TCR.
AB  - We tested the hypothesis that a cross-reactive T-cell clone could recognize HA306
      320 peptide complexed to autologous HLA-DR1101, and also to allogenic HLA-DR0402
      and HLA-DR1301 molecules, because of similar orientations of HA306-320 side
      chains in the groove of the three DR molecules. To approach peptide orientations
      in each HLA groove we compared the capacity of Ala-monosubstituted analogs to
      bind and be presented by DR1101, DR0402, and DR1301. Results indicated that the
      orientation of HA306-320 in DR1101 was grossly similar to the known orientation
      of HA307-319 in DR0101. Data suggested many similarities in peptide orientations
      in DR0402 and DR1301 as well. However, differences in binding were also observed.
      Ala substitution of Y309 had much less effect on peptide binding to DR1301 and
      DR0402 than to DR1101 and Ala-substitution of T314 increased affinity for DR1301
      but not for DR1101 and DR0402. These alterations of peptide-DR interactions were
      probably communicated to the upper peptide surface. Indeed, the levels of T-cell
      clone reactivities against analogs mutated at positions predicted to face the TCR
      were lower when complexed to allogeneic DR molecules than when complexed to
      DR1101. Yet these epitopic alterations are likely subtle, since the decreased
      reactivity of the clone to allogeneic molecules could be compensated by peptide
      substitution at Y309, predicted to face the MHC.

PMID- 8872177
TI  - The TAP complex influences allorecognition of class II MHC molecules.
AB  - The influence of the TAP complex on T-cell allorecognition of MHC class II
      molecules was examined using human B-cell lines that have mutations in the TAP 1
      or 2 genes. The TAP mutations led to the loss of allorecognition for two of 28
      anti- HLA-DR T-cell clones. Restoration of TAP expression by transfection of a
      TAP 2 cDNA clone led to recovery of the alloresponse for both clones. These
      results could be explained in two ways. First, TAP dependence could reflect
      specificity for a peptide derived from an MHC class I molecule that is less
      efficiently generated by the endocytic pathway in the TAP-deficient stimulator
      cells owing to reduction in surface class I expression. The proliferative
      responses of these clones to the TAP-deficient stimulator cells was not restored
      by rescue of cell-surface expression of class I molecules by low temperature
      culture or by the addition of class I-binding peptides. These data therefore
      favor the alternative explanation that class II loading by some peptides is TAP
      dependent. Circumstances that lead to the amplification of this minority pathway
      of endogenous presentation by class II MHC molecules may have the potential to
      interrupt self-tolerance.

PMID- 8872178
TI  - Malaria vaccine trials: the missing qualitative data.
AB  - Recent population-based efficacy trials of the synthetic malaria vaccine SPf66
      have shown restricted, if any, clinical protection against Plasmodium falciparum
      infection. Despite the well-established role of antibodies in effector responses
      against asexual blood-stage malaria parasites, the titres of anti-SPf66 IgG
      antibodies do not correlate with the ability of sera from vaccine recipients to
      inhibit parasite growth in vitro nor with partial clinical protection which could
      be detected in some trials. Qualitative or functional parameters of SP66-induced
      antibody responses, such as IgG subclass composition and affinity, may be more
      predictive of clinical protection against malaria than quantitative estimates of
      antibody concentration or titre. Since these parameters are readily estimated by
      laboratory techniques currently available, and may be modulated by changes in
      vaccination protocols and by the use of different adjuvants, a better
      understanding of qualitative antibody responses induced by SPf66 and other
      asexual blood-stage malaria vaccine candidates, and of their relationship with
      clinical protection in vivo, is urgently needed for the improvement of currently
      used immunization schedules.

PMID- 8872179
TI  - Quantifying phagocytosis of Mycobacterium avium complex by human monocytes in
      whole blood.
AB  - Studies of phagocytic efficiency in cells of the macrophage lineage have assumed
      additional importance since the discovery that HIV infection of these cells
      impairs their immune function. A rapid method has been developed for measuring
      phagocytosis of the opportunistic pathogen Mycobacterium avium complex by human
      monocytes. Fluoresceinated M. avium complex (F-MAC) was incubated with whole
      blood at 37 degrees C and the fluorescence of extracellular F-MAC was quenched
      using a vital blue stain. Monocytes were then stained with a monoclonal antibody
      (mAb) to human CD14 conjugated to phycoerythrin (PE) red cells were lysed, and
      the percentage of monocytes which had phagocytosed F-MAC was measured by flow
      cytometry. The results were reproducible in samples of blood taken from
      individual donors over a period of 1 or 2 weeks, and optimum F-MAC concentrations
      and an optimum incubation time were determined by experiment. This method has the
      advantages of requiring only a small volume of blood, not necessitating
      manipulation of cells before testing, and using a phagocytic target relevant to
      the pathogenesis of HIV infection.

PMID- 8872180
TI  - Expression of the T cell receptor delta-chain repertoire in mouse lymph node.
AB  - Despite the potential for extensive diversity of gamma delta TCR, especially for
      delta-chains, expression of the gamma delta TCR repertoire in various mouse
      epithelial tissues is highly restricted. This implies that the recognition of
      antigen by gamma delta T cells may also be limited. To date, however, few studies
      have examined gamma delta TCR diversity in peripheral lymphoid tissue. This
      report presents the V delta usage and junctional region sequences of TCR delta
      chain transcripts derived from the lymph nodes of normal (PL/J x SJ/L) F1 mice.
      Rearranged TCR V delta-C delta transcripts were amplified by PCR for TCR delta
      chain cDNA using oligonucleotide primers specific for the murine V delta 1 to V
      delta 7 genes and the C delta region. Following cloning of the polymerase chain
      reaction-amplified TCR delta cDNA, the extent of junctional diversity was
      assessed by nucleotide sequencing of the V-D-J junctions of individual TCR cDNA
      clones. With the exception of V delta 3, all V delta genes were expressed in
      mouse lymph node. Furthermore, predominant usage of J delta 1 was found in cDNA
      clones expressing V delta 2, V delta 4, V delta 5, V delta 6 and V delta 7 gene
      segments but despite this there was extensive junctional diversity of delta
      chains primarily due to the usage of multiple D delta segments and N-nucleotide
      sequence addition. In contrast, the V delta 1 cDNA clones had limited
      heterogeneity consisting mostly of V delta 1 directly spliced to C delta gene
      rearrangements. These results show that the expressed murine peripheral TCR delta
      chain repertoire is extremely diverse indicating that gamma delta T cells may
      potentially recognize a large number of antigens, and play an important role in
      contributing to host immune responses.

PMID- 8872181
TI  - Exacerbation of invasive aspergillosis by the immunosuppressive fungal
      metabolite, gliotoxin.
AB  - Invasive aspergillosis is a significant cause of death in immunocompromised
      individuals. The majority of strains of the main causative agent, Aspergillus
      fumigatus, produce gliotoxin, a secondary metabolite with demonstrated in vitro
      immunosuppressive activity. Pretreatment of normally resistant mice with a single
      injection of a sublethal dose of gliotoxin was sufficient to make them
      susceptible to infection and subsequent death, after challenge with A. fumigatus
      spores. Animals infected with the non-gliotoxin producing strain survived
      significantly longer than those infected with a gliotoxin producer. We propose
      that the release of gliotoxin by A. fumigatus hyphae during infection can
      exacerbate the pathogenesis of aspergillosis.

PMID- 8872182
TI  - Modulation of immune responses by bovine beta-casein.
AB  - The present reports the influence of bovine beta-casein on in vitro and in vivo
      immune responses. Bovine beta-casein showed an inhibitory effect on ovine
      neutrophil chemotaxis but had an enhancing effect on superoxide production by
      neutrophils. In response to mitogenic stimulation, the proliferative response of
      both T and B lymphocytes was significantly enhanced by beta-casein. While beta
      casein had no significant effects on IFN gamma production by ovine blood
      lymphocytes, and TNF alpha production and MCH Class II antigen expression by
      ovine bronchoalveolar macrophages, it enhanced IL-1 beta production by the
      macrophages, beta-casein also had no influence on bovine NK cell activity against
      a virally-infected cell line. Interestingly, beta-casein was found to reduce the
      adjuvant effect of matrix immune stimulating complexes (ISCOM) on anti-ovalbumin
      antibody response in mice when given intramuscularly. Taken together, the results
      suggest that bovine beta-casein had selective modulating effects in vitro on both
      innate and adaptive immune responses in ruminants, whereas systemic
      administration of beta-casein, that might have a depressive effect on adjuvant
      activity, requires further study.

PMID- 8872183
TI  - The PCR typing of MHC-DRB genes in the sheep using primers for an intronic
      microsatellite: application to nematode parasite resistance.
AB  - The strong association between polymorphisms in an intronic microsatellite and
      the coding sequences for (BoLA)-DRB3 genes, previously described for
      demonstrating alleles of class II major histocompatibility complex (MHC) in the
      cow, was examined in sheep to see if similar polymorphisms could be demonstrated
      in the DRB region of the MHC. The bovine primes LA53 and LA54, previously used to
      amplify the bovine DRB3 microsatellites, were used with DNA from Australian
      sheep, eight DRB alleles were identified by length polymorphisms of polymerase
      chain reaction (PCR) products amplified from the DRB microsatellite region.
      Incomplete amplification of both alleles was sometimes found for sheep DNA
      samples using bovine primers, so a modified primer (LA53b) was used, and found to
      amplify the microsatellite next to intron 2 of the MHC more reliably than the
      LA53 primer. Two additional primers (LA31 and LA32), used in amplification of the
      exon 2 region of bovine DRB3, were used in the sheep, and the PCR products were
      analysed by single-stranded conformation polymorphism (SSCP). These primers
      successfully amplified the variable region of the ovine DRB region coded by exon
      2, and the SSCP technique demonstrated polymorphisms with sheep DNA. Family
      studies demonstrated the segregation of alleles, by amplification both of
      intronic microsatellites and of the exon 2 variable region. Close correspondence
      was found between the two regions for several alleles, suggesting that the
      intronic microsatellites were closely linked to DRB-variable region alleles.
      Three families of Merino sheep with different antibody responses to intestinal
      nematode parasites were examined. The sire group with the highest antibody levels
      possessed two microsatellite alleles of closely similar length (alleles 3 and 4)
      inherited from the sire and present in high frequency in the lambs. In contrast,
      the other two sires did not possess these two alleles and the alleles were in low
      frequency in their progeny. Further studies are required in unrelated sheep to
      confirm whether these two alleles are associated with resistance to nematode
      parasites.

PMID- 8872184
TI  - IgE, allergies and helminth parasites: a new perspective on an old conundrum.
AB  - This paper analyses the association between infection with helminth parasites,
      the elevated production of IgE and the expression of allergies. Interpretations
      of this interaction have taken place in a scientific environment whose most
      secure element is the immunochemistry of allergic reactions resulting in a
      substantial body of literature that has sought a biological role for allergic
      reactivity in protective immunity directed against helminth parasites. While the
      association between helminth infections and elevated levels of IgE, mast cells
      and eosinophils is well established, a functional role for allergic reactions in
      protection against helminths has eluded experimental proof. Instead of this
      hypothesis, it is proposed that allergic reactivity is rarely present in helminth
      infected individuals because allergic reactions do not function to regulate
      helminth infections. Data from many sources are used to establish that the
      'normal' state of all mammals is to be infected with helminth parasites from
      shortly after birth until well into adulthood. Only in the last 100 years or so
      have people living in areas of high development with sophisticated water and
      sewage systems been able to escape helminth infection. Allergies are as
      conspicuously present in these human populations as they are absent in
      populations that are still regularly exposed to helminths. Furthermore, in
      populations with endemic helminthoses there is little overt expression of
      allergic pathology that could be connected to the acquisition or elimination of
      helminth parasites. Based on these observations, it is suggested that endemic
      helminthoses activate the Th2 system, particularly at mucosal surfaces, to
      provide a different level of immunological homeostasis than currently occurs in
      developed societies. Under these conditions, mast cells, eosinophils and IgE
      rarely participate in reactions that we would recognize as 'allergic', although
      their participation in the control of helminth infections is still envisaged.
      Allergic reactions are considered to be a purely pathologic consequence of the
      disruption of this homeostatic mechanism and are not protective at all for the
      individual expressing them. This interpretation is derived from the immunobiology
      of the host-parasite interaction rather than the biology of allergies and should
      lead to new concepts regarding both allergic disease and the role of helminth
      infections in human and animal populations.

PMID- 8872185
TI  - The effect of BCG, zymosan and Coxiella burnetti extract on Eimeria infections.
AB  - Infection of animals with species of Eimeria induces a hyper-reactivity to
      endotoxin as manifest by a greatly increased capacity of infected animals to
      produce TNF in response to LPS in vivo compared with uninfected animals. This
      finding indicates priming for hyperactivation of macrophages by Eimeria infection
      and raises the possibility that non-specific triggering of macrophages by agents
      such as Bacille Calmette-Guerin (BCG), zymosan or Coxiella burnetti extract may
      be a simple means of control for coccidiosis. However, all of these agents
      enhanced oocyst excretion in mice, rats or chickens infected with Eimeria
      vermiformis, Eimeria nieschulzi or Eimeria tenella, respectively, without
      affecting the patent period.

PMID- 8872186
TI  - Evolution of MHC class I genes in higher primates.
AB  - The classical major histocompatibility complex (MHC) class I genes are conserved
      in higher primates. Motifs common to human, chimpanzee and gorilla alleles
      indicate that class I alleles diverged from ancestral sequences that existed
      before separation of these species. Analysis of native human populations such as
      Australian Aborigines and Amerindians shows that HLA-B is characterized by rapid
      generation of new alleles. HLA-A and -C appear to be evolving more slowly.
      Comparison of alleles for orthologous class I genes in humans and other primates
      confirms that similar mechanisms contribute to the generation of new alleles in
      these species.

PMID- 8872187
TI  - Heavy-chain variable regions in carcharhine sharks: development of a
      comprehensive model for the evolution of VH domains among the gnathanstomes.
AB  - We determined the sequence of 18 DNA clones encoding VH regions of sandbar shark
      and bull shark. All of these sequences exhibit key structural coding features
      characteristic of known VH genes of higher vertebrates. These VH sequences
      disclosed considerable diversity, and can be divided into six families according
      to the criterion of 80% DNA sequence identity. The overlapping of some VH gene
      clones to two or more families is a particular feature found in carcharhine
      sharks, which suggests that VH diversification is a continuing process. The basic
      sequence patterns of heavy-chain V regions found in all representative
      gnathanstomes and in VH of the shark heavy immunoglobulin IgW provides evidence
      for selection of canonical residues in all VH structures. Elasmobranch VH
      sequences can be divided into two classes or clans, one comprising the
      'classical' VH set and the other comprising VHS related to those of IgW (V
      omega). Phylogenetic analyses place the VH cluster as the root of all the classic
      VHS and indicates that the V omega set is most probably that of the primordial
      heavy chain.

PMID- 8872188
TI  - NK-like activity against allogeneic tumour cells demonstrated in the spleen of
      control and thymectomized Xenopus.
AB  - This paper addresses the issue of natural killer (NK) cell evolution by searching
      for NK-like activity in an amphibian representative, the immunologically well
      characterized clawed frog, Xenopus laevis. Using in vitro 6 h 51chromium release
      assays, we have shown that splenocyte effectors from early thymectomized (Tx)
      year-old frogs, but not from control siblings, are able to spontaneously lyse
      allogeneic thymus tumour cell lines that lack MHC antigen expression. Such lytic
      capacity can be readily induced in control Xenopus and elevated in Tx frogs by a
      single injection of tumour cells, with maximal splenocyte cytotoxicity occurring
      3 days postinjection, the amount of 51Cr-release correlating directly with
      effector: target ratios. Splenocytes, even those from tumour-injected frogs, are
      unable to lyse allogeneic splenic lymphoblasts or erythrocyte targets, even when
      the latter are coated with IgY (the Xenopus IgG equivalent); moreover, we were
      unable to demonstrate any splenocyte-induced lysis of the human NK cell target
      K562. Lymphokine-activated killing (LAK) in Xenopus is suggested, since Tx
      splenocytes cultured in cytokine-rich medium (from concanavalin A-stimulated
      control splenocytes) display significantly elevated killing of allogeneic tumour
      targets. Flow cytometric analysis highlights the loss of T cell markers from the
      spleen of Tx frogs and reveals a variable staining pattern of both control and Tx
      splenocytes when treated with a mAb that binds to both fish non-specific
      cytotoxic cells and human NK cells. Prospects for identifying the cellular basis
      of NK-like activity in Xenopus are discussed in the light of these experiments.

PMID- 8872189
TI  - A partial sequence for nitric oxide synthase from a goldfish (Carassius auratus)
      macrophage cell line.
AB  - Expression of inducible nitric oxide synthase (iNOS) mRNA was detected in a
      recently developed goldfish macrophage cell line by RT-PCR, using degenerate
      primers designed against conserved nucleotide motifs within the different
      mammalian isoforms of NOS. Increased expression of iNOS poststimulation with LPS
      was found, and suggests that it is a functional enzyme in goldfish macrophages,
      supporting the view that iNOS regulation is pretranslational. The nucleotide
      sequence translated in one reading frame with no stop codons to produce a partial
      peptide containing 164 amino acids, with highest homology (85%) to a recently
      identified rainbow trout iNOS sequence. The peptide translation also gave an
      insight into the conservation of binding motifs, since two cofactor binding sites
      were present in the amplified PCR product (FMN and calmodulin). In addition, a 42
      aa motif present in the region just upstream of the FMN binding motif of
      mammalian endothelial and neuronal NOS isoforms was absent in the translation, in
      agreement with every published sequence for iNOS. Finally, the translation was
      used to construct an unrooted phylogenetic tree.

PMID- 8872190
TI  - Optimization and smoothing techniques in movement analysis.
AB  - This paper deals with accurate estimation of the degrees of freedom (DOF) of a
      body segment, starting from the trajectories of clusters of markers acquired with
      a suitable measurement system. The most commonly employed estimation procedures
      involve two sequential steps, a trajectory smoothing algorithm and a DOF
      reconstruction routine. Three optimized smoothing and reconstruction schemes are
      described, analyzed and tested and their performances are compared with each
      other and with those of a more traditional technique which contains no
      optimization criteria. All three schemes include an iterative, weighted-least
      squares DOF reconstruction routine and a self-tuning, zero-phase-shift, 4th-order
      Butterworth filter. Both routines are extensively described and validated on the
      basis of numerically-simulated marker trajectories. Test results, analyzed on a
      statistical basis, show that the use of an optimization routine provides a
      visible improvement in DOF reconstruction. This performance has also been
      confirmed using stereophotogrammetric data collected on a subject wearing an
      external fracture fixation device which provides reference values for the bone
      DOF. Angular DOF estimated applying the optimized method to skin technical
      clusters are much closer to the reference values than the non-optimized values.
      Smoothing of data further improves the reconstruction accuracy while a far less
      crucial role is played by the order in which smoothing and reconstruction
      routines are applied.

PMID- 8872191
TI  - A method for the estimation of the hemoglobin distribution in gastroscopic
      images.
AB  - The assessment of blood flow in the gastrointestinal mucosa could be a useful
      indicator for the diagnosis and treatment of several diseases, such as ulcers,
      gastritis, colitis or early cancer. The quantity of blood flow is roughly
      estimated by computing the spatial hemoglobin distribution in the mucosa. The
      method presented here enables a practical realization by calculating
      approximately the hemoglobin concentration based on a spectrophotometric analysis
      of endoscopic true-color images, which are recorded during routine examinations.
      A system model based on the reflectance spectroscopic law of Kubelka-Munk is
      derived, which enables an estimation of the hemoglobin concentration by means of
      the color values of the images. Additionally, a transformation of the color
      values is developed, in order to improve the luminance independence. Applying
      this transformation and estimating the hemoglobin concentration for each pixel of
      interest, the hemoglobin distribution can be computed. The results obtained are
      mostly independent of luminance. An initial validation of the method is made by a
      quantitative estimation of the reproducibility.

PMID- 8872192
TI  - Transfer of hypercalcemia discriminant functions between local hospitals.
AB  - Transferability of discriminant functions is potentially useful both from an
      economical point of view and because, in general, medical knowledge, in this case
      discriminant functions, should be transferable. In the present study we have
      evaluated the transferability of discriminant functions, estimated from routine
      laboratory analysis, age and sex in two consecutively recorded populations with
      hypercalcemia including 162 and 257 patients with hypercalcemia. Discriminant
      functions were developed for each sex to distinguish between hypercalcemia
      associated with malignancy and hypercalcemia associated with other medical
      diseases. The total diagnostic accuracy in Herlev was 82 and 78%, in women and
      men, and increased to 87 and 86% in both sexes considering cases classified with
      posterior probability levels of 60%. In Hvidovre the total diagnostic accuracy
      was 81 and 84% in women and men, and increased to 83 and 89% at posterior
      probability levels higher than 60%. Transfer of the discrimination functions
      between the hospitals was followed by a decrease in diagnostic accuracy of 6-16%.
      At a posterior probability of 60% the diagnostic accuracies were 79% or more in
      the receiving hospital, in both sexes, except for men in Hvidovre. In relation to
      these results the concept of genuine and non-genuine transfer factors is
      introduced and discussed.

PMID- 8872193
TI  - A hypermedia system for parasite identification.
AB  - In this paper a hypermedia system for parasite identification is described. The
      knowledge base is relative to the class of the Trematoda parasites and reports
      agent, vector, disease, related category of the International Classification of
      Diseases and geographic area. A graphic user-friendly human-machine interface has
      been realized for this system.

PMID- 8872194
TI  - A Dutch medical language processor.
AB  - This paper describes the current state of a medical language processor for Dutch.
      The goal is to implement a language specific front-end compatible with some
      existing applications that aim at the intelligent extraction and processing of
      information from patient discharge summaries. A complete chain for processing and
      understanding Dutch medical documents will be the ultimate result. The text
      focuses mainly on the language specific aspects of the language processing chain.
      Evaluation results of the already functioning components are given as well as an
      outline for future developments and enhancements. A short theoretical background
      is provided (cf. also [1-3]: Rossi Mori et al., Proc. SCAMC 90, 1990, pp. 185
      189; Wingert, in: Informatics and Medicine, an advanced course, Springer-Verlag.
      1977, pp. 579-646; Wingert, Proc. MEDINFO 80, 1980, pp. 1321-1331) before the
      description of each component in order to familiarise the non-experienced reader
      with the basic notions of computational linguistics.

PMID- 8872195
TI  - Impact of the mass media on calls to the CDC National AIDS Hotline.
AB  - This paper considers new computer methodologies for assessing the impact of
      different types of public health information. The example used public service
      announcements (PSAs) and mass media news to predict the volume of attempts to
      call the CDC National AIDS Hotline from December 1992 through to the end of 1993.
      The analysis relied solely on data from electronic databases. Newspaper stories
      and television news transcripts were obtained from the NEXIS electronic database
      and were scored by machine for AIDS coverage. The PSA database was generated by
      computer monitoring of advertising distributed by the Centers for Disease Control
      and Prevention (CDC) and by others. The volume of call attempts was collected
      automatically by the public branch exchange (PBX) of the Hotline telephone
      system. The call attempts, the PSAs and the news story data were related to each
      other using both a standard time series method and the statistical model of
      ideodynamics. The analysis indicated that the only significant explanatory
      variable for the call attempts was PSAs produced by the CDC. One possible
      explanation was that these commercials all included the Hotline telephone number
      while the other information sources did not.

PMID- 8872217
TI  - Three-dimensional nasal changes following maxillary advancement in cleft
      patients.
AB  - Three-dimensional laser surface scanning of the face was performed before and
      after Le Fort I maxillary advancement in 24 patients with replaced clefts of the
      lip and palate. The surgery resulted in advancement of the upper lip and para
      alar tissues and an increase in the relative prominence of the nose within the
      face. These changes were produced at the expense of an increase in nasal width
      and a reduction in nasal tip protrusion. The changes in nasal morphology showed
      significant variation among patients.

PMID- 8872218
TI  - Temporomandibular arthropathy: correlation between clinical signs and symptoms
      and arthroscopic findings.
AB  - The clinical signs and symptoms of temporomandibular arthropathy were correlated
      with arthroscopic features of temporomandibular joint disease in 200 consecutive
      patients. The diagnostic accuracy of the selected clinical signs and symptoms was
      also tested with arthroscopy as the standard, and sensitivity (SE), specificity
      (SP), positive predictive value (PPV), and negative predictive value (NPV) were
      calculated. Pronounced osteoarthrosis was more frequently associated with joint
      crepitus (P < 0.001). Adhesions were more frequently associated with reduced
      maximum protrusion (P < 0.001). Crepitation was the only clinical sign that
      showed acceptable values for SE, SP, PPV, and NPV, and only in diagnosing
      advanced osteoarthrosis. The values for mild osteoarthrosis were low.

PMID- 8872219
TI  - Peripheral facial palsy after sagittal split ramus osteotomy for setback of the
      mandible. A case report.
AB  - The case of a 21-year-old man who underwent sagittal split setback osteotomy is
      described. He experienced facial nerve palsy 2 days after his surgery. However,
      after physical therapy and the administration of vitamins, he regained normal
      function within 3 months. The literature related to postoperative facial nerve
      paralysis is briefly reviewed.

PMID- 8872220
TI  - Simultaneous placement of endosteal implants and mandibular onlay grafting for
      treatment of the atrophic mandible. A preliminary report.
AB  - A method of placing two endosteal implants with simultaneous bone grafting to the
      anterior mandible is described. This technique is simple to use, has minimal
      morbidity, and has produced good preliminary results. Retrospectively, 18
      patients with a total of 36 implants were reviewed. An implant success rate of
      91.6% was seen at a mean follow-up time of 17 months after loading with an
      implant-supported, soft-tissue-borne overdenture.

PMID- 8872221
TI  - The role of magnetic resonance imaging and scintigraphy in the diagnosis of
      pathologic changes of the mandible after radiation therapy.
AB  - A prospective study of 85 patients with oral cancer, treated with high-dose
      radiation therapy, was performed to assess the value of magnetic resonance
      imaging (MRI) and scintigraphy for diagnosis of pathologic changes in the
      mandible. During postradiotherapeutic monitoring, radiation osteomyelitis
      occurred in 12 cases, tumor recurrences infiltrating the mandible in five cases,
      and progressive periodontal disease in nine cases. MRI permitted early diagnosis
      of radiation osteomyelitis in 11 out of 12 cases; only two cases were false
      positive. In scintigraphy with 99mTc-HDP, all alterations of the mandible, such
      as osteoradionecrosis, tumor infiltration, and periodontitis, showed a high
      uptake, resulting in a sensitivity of up to 100%, but a low specificity of 57%.
      Scintigraphy permitted assessment of the extension and location of the lesions.
      Both methods were superior to conventional radiography and clinical examination
      and should be integrated into a comprehensive follow-up program after radiation
      therapy.

PMID- 8872222
TI  - Adnexal adenocarcinoma of the upper lip.
AB  - A case of poorly differentiated adenocarcinoma of adnexal origin in the upper lip
      of a man aged 75 is reported which on presentation and initial biopsy was thought
      to be a salivary neoplasm. He had been aware of the lesion for 10 years but had
      sought treatment because of recent increase in size of the tumour. He
      subsequently developed bilateral metastases in cervical nodes. The
      histopathologic features and relationship of the tumour to the orbicularis oris
      muscle were consistent with a poorly differentiated adnexal adenocarcinoma of
      sweat-gland origin. Although carcinomas of skin adnexae are rare they should be
      considered in the differential diagnosis of tumours in the orofacial region.

PMID- 8872223
TI  - Ameloblastic fibroma: a follow-up of six cases.
AB  - Six cases of ameloblastic fibroma of the jaw are reported, and the radiographic
      and histologic features and clinical symptoms are described. A conservative
      surgical approach, including enucleation and mechanical curettage of the
      surrounding bone, appeared to be successful for these patients.

PMID- 8872224
TI  - Osteochondroma of the mandibular condyle. A case report.
AB  - Osteochondroma of the mandibular condyle is extremely rare and may cause signs
      and symptoms like those seen in patients with temporomandibular joint
      dysfunction. Differentiation between osteochondroma and condylar hyperplasia is
      not possible on histologic grounds alone, but the radiographic and intraoperative
      findings together are usually sufficient to establish a definite diagnosis.

PMID- 8872225
TI  - Pleomorphic adenoma of the palate in children: report of a case.
AB  - Salivary gland tumors are rare in infancy, and almost all of them are found in
      the parotid gland. Minor salivary gland tumors are even more rare, pleomorphic
      adenoma being the most frequently involved tumor. Only six well-described cases
      of pleomorphic adenoma arising in the palate have been reported in children. A
      case occurring in a 16-year-old boy is presented.

PMID- 8872226
TI  - Congenital teratoma of the cheek: report of a case.
AB  - An atypical teratoma resembling a breast-like malformation of the cheek is
      described.

PMID- 8872227
TI  - Polyactive as a bone-filler in a beagle dog model.
AB  - Calcification is a crucial step in the bone-bonding mechanism of PEO/PBT hydrogel
      copolymers (Polyactive, a new generation of bone-fillers. A beagle dog study was
      conducted to determine whether the preoperative presence of a calcium phosphate
      layer (precalcification) on a PEO/PBT 80/20 copolymer would further increase the
      bone-bonding rate. Standard bone cavities were filled with either precalcified or
      nonprecalcified porous cylindric PEO/PBT 80/20 implants, or hydroxyapatite
      granules held together with PEO/PBT 70/30, or were left unfilled. A significantly
      higher percentage of mineralized component was present in the cavities filled
      with the precalcified PEO/PBT 80/20 copolymer than in the control defects. As a
      result of swelling by fluid-uptake, the press-fit inserted copolymer implants
      showed a significant reduction in pore size, thus preventing optimal bone
      ingrowth. Both precalcification of the copolymer and underfilling of the defect,
      to create space for the copolymer to increase in diameter, stimulate
      postoperative calcification and bone ingrowth in PEO/PBT 80/20 copolymers.

PMID- 8872228
TI  - Xenogeneic moose (Alces alces) bone morphogenetic protein (mBMP)-induced repair
      of critical-size skull defects in sheep.
AB  - A standardized skull defect in adult sheep was used to test the healing capacity
      of xenogeneic, partially purified, moose-derived bone morphogenetic protein
      (mBMP) extracted from the fresh long bones of moose (Alces alces) calves. An
      amount of 52 mg of mBMP mixed with 13 mg of purified type IV collagen (5:1)
      (mBMP/COL) in gelatin capsules was implanted into six 22-mm-diameter skull
      defects in adult sheep for comparison with six defects implanted with fresh
      autogenous bone marrow (BM) and six other controls implanted with a gelatin
      capsule containing 13 mg of type IV collagen (C). The amount of new bone formed
      was quantified from radiographs by computerized image analysis and histology. The
      healing percentage in the mBMP/COL group was significantly higher (93.18 +/-
      4.51%) than in the BM (33.17 +/- 20.05%) or C group (31.32 +/- 17.41%) at 16
      weeks after implantation. The difference between BM and C was not statistically
      significant. The level of anti-BMP antibody in the serum showed a significant
      increase in the group implanted with mBMP, but returned to normal after 6 weeks.
      The experiment demonstrated that xenogeneic mBMP possesses a strong
      osteoinductive capacity and weak immunogenicity.

PMID- 8872229
TI  - Femoral shaft reconstruction using tissue-engineered growth of bone.
AB  - Tissue engineering is an interdisciplinary field that applies the principles and
      methods of engineering and the life sciences to the development of biologic
      substitutes. Bovine periosteum-derived cells were cultivated in vitro, put onto
      bioresorbable polymer fiber constructs, and allowed to grow until most of the
      fibers were coated with multiple layers of osteoblasts. Standardized 9-mm
      nonhealing defects were created in 24 male athymic rats femurs and bridged with
      titanium miniplates. In 12 animals, the defects were filled with polymer
      constructs containing periosteum-derived cells (experimental group); in another
      12 animals, the defects were either left unfilled (control group I) or filled
      with polymer templates alone (control group II). After 12-week in vivo
      implantation, the new bone produced bridged the surgically created defects
      completely in seven of 10 cases. The animals of the control groups did not show
      significant bone formation in the gap. Histologic evaluation revealed bone
      formation in all experimental specimens with rests of cartilage islands showing
      hypertrophying chondrocytes indicative of enchondral bone formation. Tissue
      engineered growth of bone resulted in healing of large segmental bone defects in
      an orthotopic site in an animal model. The findings of this study support
      potential applications of the technique of tissue-engineered growth of bone to
      clinical situations where local bone formation is needed.

PMID- 8872230
TI  - Influence of mono- and bicortical anchorage on the integration of titanium
      implants. A study in the rabbit tibia.
AB  - The study aimed to evaluate the removal torque and bone tissue response to
      titanium implants supported by one or two cortical layers. A total of 72 screw
      titanium implants, either 10 or 16 mm in length and 3.75 mm in diameter, were
      inserted in right and left tibiae of 18 adult New Zealand rabbits. The implants
      engaged either one or two cortical layers, and the animals were allowed a healing
      period of 6 or 12 weeks. The degree of integration was assessed by measuring the
      removal torque with a torque gauge manometer. Histomorphometric calculations were
      also performed in 10-microns-thick ground sections. All implants were clinically
      stable at the end of the experiment. The removal torque was two times higher for
      the bicortical implants after 6 weeks, and three times higher after 12 weeks,
      than for the monocortical ones. The 16-mm implants also showed a statistically
      higher amount of bone contact and bone area after 6 and 12 weeks, respectively,
      than the short ones. The results support bicortical anchorage of implants also in
      the clinical situation.

PMID- 8872231
TI  - Morphology of the mandibular fossa and the articular eminence in
      temporomandibular joints with anterior disk displacement.
AB  - The depth, length, and depth:length ratio of the mandibular fossa, and the angles
      of the posterior slope of the articular eminence were measured for 91
      temporomandibular joints (TMJ) with anterior disk displacement (ADD) in 79 female
      patients with TMJ dysfunction. As a control, 48 joints in 24 females without TMJ
      dysfunction were similarly measured. One of the angeles of the posterior slope of
      the articular eminence was larger for joints with ADD than for the controls (P <
      0.01, Student's t-test). There were no other statistically significant
      differences between the two groups. Among the 91 joints with ADD, there was no
      statistically significant difference in any variable between joints with ADD with
      reduction (n = 46) and those with ADD without reduction (n = 45); likewise, there
      was no association between the magnitude of angle of the posterior slope of the
      articular eminence and overjet, overbite, canine relationship, or molar
      relationship.

PMID- 8872232
TI  - Experimental study on necrotizing sialometaplasia of the palate in rats. Role of
      local anesthetic injections.
AB  - The effect of local anesthetic injections in the palate of rats was studied by
      light microscopy and immunohistochemistry with antibody to proliferating cell
      nuclear antigen (PCNA). The results of this study suggest that local anesthetic
      injections could be one of the causes of necrotizing sialometaplasia.

PMID- 8872233
TI  - Development of a national clinical logbook system for oral and maxillofacial
      surgery trainees--the RACDS, OMS system.
AB  - The development of a national computer database for trainees' clinical logbooks
      is described. Data are collected contemporaneously by trainees under the
      supervision of the director of their training programme. The full scope of oral
      and maxillofacial surgery is covered, and a national standard of experience has
      been developed. The benefits of this system to individual trainees, training
      institutions, and national educational bodies are presented.

PMID- 8872234
TI  - Determination of Phenmetrazine in urine by gas chromatography-mass spectrometry.
AB  - A sensitive and simple gas chromatographic--mass spectrometric method is
      described for the determination of the central nervous system (CNS) stimulant
      phenmetrazine in urine. The extraction and derivatization were combined into a
      single step with isooctane and methyl chloroformate. The limit of quantitation
      was 0.05 micrograms/mliters urine, and the method was linear up to 100
      micrograms/mliters. The coefficients of variation (CV) for within-day runs were
      1.2% and 2.4% (n = 5) for two controls containing 1.0 micrograms/mliters and 50
      micrograms/mliters, respectively. During a six-month period, the same controls
      showed CVs of 9.1% and 8.7%, respectively (n = 40), indicating a somewhat lower
      between-run precision. Phenmetrazine was present in 83 out of 3000 urine samples
      that were screened for CNS stimulants during this period, and the concentrations
      ranged from 0.5-370 micrograms/mliters.

PMID- 8872235
TI  - Simultaneous determination of illicit drugs in human urine by liquid
      chromatography-mass spectrometry.
AB  - The method for simultaneous determination and confirmation of illicit drugs
      (e.g., methamphetamine, amphetamine, ephedrine, methylephedrine, morphine,
      morphine-3-glucuronide, morphine-6-glucuronide, 6-acetylmorphine, cocaine, and
      benzoylecgonine) in human urine by thermospray liquid chromatography-mass
      spectrometry (LC-MS) was studied. The LC-MS separation was performed on a
      reversed phase column (L-column ODS; 150 mm x 4.6-mm i.d.) using a gradient
      mobile phase system of 100mM ammonium acetate for 1 min then linear ramps to
      100mM ammonium acetate including 40% acetonitrile at 20 min. Extraction was
      conducted by solid-phase extraction using a Sep-pak C18 cartridge. The drugs were
      eluted with 2 mliters of 40% acetonitrile in 100 mM ammonium acetate, pH3
      (adjusted with acetic acid), from the cartridge. A 50-microL volume of the eluate
      was injected into the LC-MS. The recoveries by this extraction were 88 to 99%.
      The mass spectra of methamphetamine, amphetamine, ephedrine, methylephedrine,
      morphine, 6-acetylmorphine, cocaine, and benzoylecgonine showed the quasi
      molecular [M + H]+ ion as the base peak, whereas morphine-3-glucuronide and
      morphine-6-glucuronide showed [MH-glucuronide]+ ion as the base peak. The
      calibration graphs were linear and reproducible. Detection limits of these drugs
      ranged from 2 to 40 ng/mliters by selected ion monitoring (SIM) mode and from 50
      to 400 ng/mliters by scan mode. The coefficients of variation for the analysis of
      these drugs ranged from 4.5 to 9.5% at a concentration of 0.4 micrograms/mliters
      (n = 10).

PMID- 8872236
TI  - Determination of volume of distribution for ethanol in male and female subjects.
AB  - Ten nonalcoholic subjects gave written informed consent. Six men (aged 25-43) and
      four women (aged 25-35) were hydrostatically weighed to determine their
      percentage of body fat and lean weight. Each subject fasted for at least 10 h and
      then received an oral dose of alcohol (0.9 g per kilogram of lead body weight)
      calculated to yield a peak alcohol concentration of 0.100 g/210-L breath. Breath
      alcohol measurements were conducted at 20-min intervals until each subject's
      alcohol concentration returned to 0.000 g/210-L breath. All alcohol analyses were
      conducted on the Intoxilyzer 5000 and reported as g/210-L breath. Female subjects
      on average reached a lower peak alcohol concentration (mean, 0.086; range, 0.074
      0.091 g/210 L) than male subjects (mean, 0.096; range, 0.093-0.101 g/210 L).
      Females demonstrated a higher average rate of elimination (mean, 0.017; range,
      0.014-0.021 g/210 L) than males (mean, 0.015; range, 0.013-0.017 g/210 L). Female
      subjects on average had a higher percentage of body fat (mean, 26.0; range, 16.7
      36.8%) than males (mean, 18.0; range, 10.2-25.3%). The average volume of
      distribution (Vd), as calculated from percentage of body fat, for the women
      (mean, 0.63; range, 0.54-0.71) was less than for the men (mean, 0.69; range, 0.63
      0.76). The average Vd as calculated from linear regression of the alcohol
      concentration curve, for the women (mean 0.64, range, 0.56-0.71) was also less
      than for the men (mean, 0.72; range, 0.67-0.77). The data from this limited study
      indicate that hydrostatic weighing is an acceptable way of determining Vd for
      both men and women.

PMID- 8872237
TI  - Investigation of the effects of solution composition and container material type
      on the loss of 11-nor-delta 9-THC-9-carboxylic acid.
AB  - The loss of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) from
      solution was studied using fluorescence polarization immunoassay (FPIA)
      technology and x-ray photoelectron spectroscopy (XPS). Several materials (glass,
      silylated glass, high density polyethylene, polypropylene, polystyrene,
      polymethylmethacrylate, Teflon, and Kynar) were studied along with three solvents
      (water, urine, and Abbott cannabinoids diluent). THC-COOH losses ranging from 0
      to 9.7 ng/cm2 and concentration reductions to 46% of starting values were
      measured. XPS indicated the presence of fluorine-labeled THC-COOH at materials
      surfaces. A half-life of 10 min was calculated for THC-COOH loss from urine
      stored in high density polyethylene at room temperature. Sample handling losses
      during pipetting were determined and ranged from 1.1 to 7.9 ng per aliquot. The
      effects of sample volume and sample handling on the THC-COOH concentrations of
      controls were also investigated.

PMID- 8872238
TI  - One fatal and one nonfatal intoxication with tranylcypromine. Absence of
      amphetamines as metabolites.
AB  - Two very different cases of overdose with tranylcypromine are presented. One
      clinical case involving the ingestion of 400 mg tranylcypromine with suicidal
      intention and one fatality with a suspicion of possible tranylcypromine overdose
      were examined. Both cases showed similar blood concentrations (0.5 and 0.7 mg/L,
      respectively), but the clinical case exhibited only mild symptoms of
      intoxication. The fatality showed no other drugs that could provide an
      explanation for the death of a 40-year-old male except tranylcypromine.
      Consideration of the drug concentrations in the fatality in relation to the case
      findings and other reported data indicates the tranylcypromine overdose as the
      probable cause of death, despite the low blood concentration. In addition, we
      looked for evidence of amphetamine as a putative metabolite in both cases. No
      amphetamines were detected in the overdose cases reported here.

PMID- 8872239
TI  - Comparison of HPLC and GC-MS for measurement cocaine and metabolites in human
      urine.
AB  - High-performance liquid chromatography (HPLC) was compared with gas
      chromatography-mass spectrometry (GC-MS) for quantitation of cocaine,
      benzoylecgonine, norcocaine, and cocaethylene in urine. Calibration standards
      were prepared in human urine, and bupivacaine was added as the internal standard
      for quantitation. After solid-phase extraction, the reconstituted samples were
      divided into aliquots for analysis by HPLC and GC-MS. The analytical performance
      of the two methods were compared with regard to sensitivity, precision, and
      dynamic range. Results of GC-MS and HPLC analyses of nine urine specimens
      previously confirmed as positive for benzoylecgonine were compared. Analytical
      results by HPLC were comparable to GC-MS. Therefore, for many laboratories, HPLC
      is a useful alternative to GC-MS for measuring cocaine and metabolites in urine.

PMID- 8872240
TI  - Gas chromatographic determination of urinary o-cresol for the monitoring of
      toluene exposure.
AB  - A sensitive and reproducible gas chromatographic procedure for the quantitative
      determination of urinary o-cresol is described. The first step involves acid
      hydrolysis (2N HCl, 100 degrees C, 10 min), which yields unconjugated o-cresol.
      After extraction (methylene chloride, pH 2), the organic layer is concentrated by
      evaporation and samples are analyzed by gas chromatography-flame ionization
      detection with a DB-5 column (30 m x 0.25 mm, 0.25 microns). Initial oven
      temperature is set at 30 degrees C for 12 min and the increased 2 degrees C/min
      to 93 decrees C. 3,4-Dimethylphenol is used as the internal standard. The
      detection limit of the method is 0.36 mumol/L (1 microL injection). Additional
      validation data were obtained by analysis of urine samples collected from
      volunteers exposed to various concentrations of toluene: 10, 20, 30, 50, and 100
      ppm over 7 h. Urinary o-cresol concentrations (0-3, 3-7, 7-24, and 0-24 h) were
      highly correlated with toluene exposure.

PMID- 8872241
TI  - Normal values for pentachlorophenol in urine samples collected from a general
      population.
AB  - Aliquots of urine samples collected over a 24-h period from normal individuals
      were analyzed for pentachlorophenol (PCP). Urine samples were taken from subjects
      living in various regions (both rural and urban) throughout the province of
      Saskatchewan. Urinary PCP concentrations were determined with gas chromatography
      mass spectrometry and stable isotope dilution. The normal PCP concentrations were
      found to range from 0.05 to 3.6 ng/mliters. Because the aliquots analyzed were
      taken from 24-h sample collections, the normal range of PCP excreted on a daily
      basis was determined. A total of 69 samples taken from 26 males and 43 females
      who ranged in age from 6 to 87 years were analyzed. The average amount of
      excreted PCP was determined to be 4.3 nmol/day.

PMID- 8872242
TI  - Determination of ester-type local anesthetic drugs (procaine, tetracaine, and T
      caine) in human serum by wide-bore capillary gas chromatography with nitrogen
      phosphorus detection.
AB  - A sensitive method for simultaneous determination of ester-type local anesthetic
      drugs (procaine, tetracaine, and T-caine) has been developed using wide-bore
      capillary gas chromatography with nitrogen-phosphorus detection (GC-NPD). The
      extraction procedure, the experimental conditions for heptafluorobutyryl (HFB)
      derivative formation, and the percentage of the ester-type local anesthetic drugs
      from the human serum are described. The HFB derivatives of ester-type local
      anesthetic drugs showed sensitivity of approximately 2-3 fold higher than that
      without derivatization. The detection limits of HFB derivatives of the ester-type
      local anesthetic drugs were approximately 60-70 pg on column. Recoveries from the
      human serum were 85-94%. This method could be used to determine concentrations as
      low as 24-28 ng/mliters of the ester-type local anesthetic drugs.

PMID- 8872243
TI  - Detection of LSD and metabolite in rat hair and human hair.
AB  - To examine the feasibility of detecting lysergic acid diethylamide (LSD) and its
      metabolites in hair, LSD was administered to rats with pigmented hair at 0.05,
      0.1, 0.5, 1, and 2 mg/kg intraperitoneally once per day for 10 successive days.
      The rats were shaved just before the first administration, and newly grown hair
      was collected 4 weeks later. After being washed with 0.1% sodium dodecyl
      sulfonate and water and being dried in a desiccator, each 20-mg hair sample was
      extracted with 2 mliter methanol-5N HCl (20:1) under ultrasonication for 1 h and
      stored at room temperature for 14 h. The extract was evaporated to dryness,
      extracted from 0.1M NaOH with dichloromethane, and derivatized with a mixture of
      trimethylsilylimidazole, bis-(trimethylsilyl)acetamide, and trimethylchlorosilane
      (3:3:2, v/v/v) for gas chromatographic-mass spectrometric (GC-MS) analysis using
      LSD-d10 or lysergic acid methylpropylamide (LAMPA) as the internal standard.
      Selected ions were monitored at m/z 395, 293, and 279 for TMS-LSD and at m/z 381,
      279, and 254 for the trimethylsilyl derivative of N-demethyl-LSD (TMS-norLSD).
      LSD and norLSD were also detected by high-performance liquid chromatography
      (HPLC) with fluorometric detection (excitation, 315 nm; emission, 420 nm). LSD
      was detected in the rat hair following the lowest dose (0.05 mg/kg), whereas
      norLSD was only detectable in the hair following the highest dose (2 mg/kg). The
      same GC-MS and HPLC assays were applied to the analysis of hair from 17 self
      reported LSD users, and LSD was detected in two of the samples.

PMID- 8872244
TI  - Dilution of blood collected for medicolegal alcohol analysis by intravenous
      fluids.
AB  - Two case reports of the dilution by intravenous fluids of blood samples collected
      for medicolegal alcohol analysis are presented. The forensic significance of the
      findings is discussed.

PMID- 8872245
TI  - Unsuspected ethanol ingestion through soft drinks and flavored beverages.

PMID- 8872246
TI  - High concentration of ciprofloxacin in urine invalidates EMIT results.

PMID- 8872247
TI  - A 3D-LDA study of the relation between wall shear stress and intimal thickness in
      a human aortic bifurcation.
AB  - A realistic model experiment on hemodynamics was performed to study correlations
      between wall shear stresses measured in a cast model of the aortic bifurcation
      and intimal thickness at each corresponding site of the native blood vessel from
      which the cast had been made. An elastic model of a 54 year old human aortic
      bifurcation was made of a polyurethane elastomer using a dipping method, and was
      perfused with Newtonian or non-Newtonian fluid under physiologic pulsatile flow
      condition. Local flow velocities were measured with an optical-fibered, 3
      dimensional laser Doppler anemometer (3D-LDA) to determine wall shear stresses.
      Distribution of intimal thickness was determined using histological specimens of
      the native blood vessel. The results obtained are: 1) Non-Newtonian fluid
      rheology increased wall shear stresses; 2) Positive correlations were observed
      between intimal thickness and the maximum instantaneous wall shear stress, and 3)
      However, if we take only the data from the circumference at the level of the flow
      divider tip, there were negative correlations between them.

PMID- 8872248
TI  - Steady flow in an aneurysm model: correlation between fluid dynamics and blood
      platelet deposition.
AB  - Laminar and turbulent numerical simulations of steady flow in an aneurysm model
      were carried out over Reynolds numbers ranging from 300 to 3600. The numerical
      simulations are validated with Digital particle Image Velocimetry (DPIV)
      measurements, and used to study the fluid dynamic mechanisms that characterize
      aneurysm deterioration, by correlating them to in vitro blood platelet deposition
      results. It is shown that the recirculation zone formed inside the aneurysm
      cavity creates conditions that promote thrombus formation and the viability of
      rupture. Wall shear stress values in the recirculation zone are around one order
      of magnitude less than in the entrance zone. The point of reattachment at the
      distal end of the aneurysm is characterized by a pronounced wall shear stress
      peak. As the Reynolds number increases in laminar flow, the center of the
      recirculation region migrates toward the distal end of the aneurysm, increasing
      the pressure at the reattachment point. Under fully turbulent flow conditions (Re
      = 3600) the recirculation zone inside the aneurysm shrinks considerably. The wall
      shear stress values are almost one order of magnitude larger than those for the
      laminar cases. The fluid dynamics mechanisms inferred from the numerical
      simulation were correlated with measurements of blood platelet deposition,
      offering useful explanations for the different morphologies of the platelet
      deposition curves.

PMID- 8872249
TI  - Effects of particle concentration on the partitioning of suspensions at small
      divergent bifurcations.
AB  - Experimental results are reported for the low Reynolds number flow of a
      suspension of spherical particles through a divergent capillary bifurcation
      consisting of a straight tube of circular cross-section that splits to form two
      tubes of equal diameter. The partitioning of particles between the downstream
      branches of the bifurcation is measured as a fraction of the partitioning of
      total volume (particles + suspending fluid) between the branches. Two bifurcation
      geometries are examined: a symmetric Y-shaped bifurcation and a nonsymmetric T
      shaped bifurcation. This experiment focuses on the role of hydrodynamic
      interactions between particles on the partitioning of particles at the
      bifurcation. The particle diameter, made dimensionless with respect to the
      diameter of the branch tubes, ranges from 0.4 to 0.8. Results show that
      hydrodynamic interactions among the particles are significant at the bifurcation,
      even for conditions where interactions are unimportant in the straight branches
      away from the bifurcation. As a result of hydrodynamic interactions among
      particles at the bifurcation, the partitioning of particles between the branches
      is affected for particle volume fractions as small as 2 percent. The experimental
      results show that the effect of particle volume fraction is to diminish the
      inhomogeneity of particle partitioning at the bifurcation. However, the magnitude
      of this effect depends strongly on the overall shape of the bifurcation geometry,
      and, in particular on the angles between the branches.

PMID- 8872250
TI  - Separation of arterial pressure waves into their forward and backward running
      components.
AB  - A new separation technique has been developed to determine the forward and
      backward running arterial pressure wave components. It takes into account
      friction as well as nonlinear effects due to convective acceleration and to the
      pressure dependence of the arterial compliance. The new method is a combination
      of two methods treating friction and nonlinearities separately. The method
      requires the measurements of pressure and flow at one location as well as the
      knowledge of the area-pressure relationship. The validity of the method was
      tested by a simulation experiment in which the forward and backward waves were
      known a priori. It was shown that the new method is significantly more accurate
      in the predictions of the forward and backward waves when compared to the
      classical method assuming linearity and no dissipation. The new wave separation
      method was also applied to simulated aortic waves for (a) a healthy subject and
      (b) a subject with decreased compliance. Comparison with the classical linear
      method showed that neglecting nonlinearities leads to an overestimation of the
      forward and backward pressure wave amplitudes. The errors, however, were in the
      order of 5 to 10 percent. We concluded that, for most clinical purposes, the
      improvement using the nonlinear method is of the same magnitude as experimental
      errors, and thus the linear method would suffice.

PMID- 8872251
TI  - Numerical investigation of steady flow in proximal and distal end-to-side
      anastomoses.
AB  - Steady flow in model proximal and distal end-to-end bypass anastomoses were
      simulated numerically. The predictions were compared to whole field measurements
      of the flow in in vitro models, and were shown to match well the general features
      of the measured flows. The predictions confirmed that the flows in end-to-side
      anastomoses are complex and three dimensional, and contain areas that could allow
      long residence times. Careful examination of the predictions revealed certain
      features of the flows not seen easily in the experiments. Shear stress and
      pressure on the vessel walls were predicted, and areas known to be prone to
      intimal hyperplasia were shown to correspond to areas of high spatial gradient of
      shear stress. Two anastomosis angeles, 30 and 45 deg, were considered, and it was
      shown that the more acute angle may have some benefit in terms of the levels of
      shear gradients and the power required to drive the flow through the anastomosis.

PMID- 8872252
TI  - Classification of pulsating flow patterns in curved pipes.
AB  - The fully developed periodic laminar flow of incompressible Newtonian fluids
      through a pipe of circular cross section, which is coiled in a circle, was
      simulated numerically. The flow patterns are characterized by three parameters:
      the Womersley number Wo, the Dean number De, and the amplitude ratio beta. The
      effect of these parameters on the flow was studied in the range 2.19 < or = Wo <
      or = 50.00, 15.07 < or = De < or = 265.49 and 0.50 < or = beta < or = 2.00, with
      the curvature ratio delta fixed to be 0.05. The way the secondary flow evolved
      with increasing Womersley number and Dean number is explained. The secondary flow
      patterns are classified into three main groups: the viscosity-dominated type, the
      inertia-dominated type, and the convection-dominated type. It was found that when
      the amplitude ratio of the volumetric flow rate is equal to 1.0, four to six
      vortices of the secondary flow appear at high Dean numbers, and the Lyne-type
      flow patterns disappear at beta > or = 0.50.

PMID- 8872253
TI  - Characterization of blood flow turbulence with pulsed-wave and power Doppler
      ultrasound imaging.
AB  - Blood turbulence downstream of a concentric 86 percent area reduction stenosis
      was characterized using absolute and relative Doppler spectral broadening
      measurements, relative Doppler velocity fluctuation, and Doppler backscattered
      power. Bidimensional mappings of each Doppler index were obtained using a 10 MHz
      pulsed-wave Doppler system. Calf red cells suspended in a saline solution were
      used to scatter ultrasound and were circulated in an in vitro steady flow loop
      model. Results showed that the absolute spectral broadening was not a good index
      of turbulence because it was strongly affected by the deceleration of the jet and
      by the shear layer between the jet and the recirculation zones. Relative Doppler
      spectral broadening (absolute broadening divided by the frequency shift),
      velocity fluctuation, and Doppler power indices provided consistent mapping of
      the centerline axial variation of turbulence evaluated by hot-film anemometry.
      The best agreement between the hot-film and Doppler ultrasound methods was
      however obtained with the Doppler back-scattered power. The most consistent
      bidimensional mapping of the flow characteristics downstream of the stenosis was
      also observed with the Doppler power index. The relative broadening and the
      velocity fluctuation produced artifacts in the shear layer and in the
      recirculation zones. Power Doppler imaging is a new emerging technique that may
      provide reliable in vivo characterization of blood flow turbulence.

PMID- 8872254
TI  - The influence of shape on the stresses in model abdominal aortic aneurysms.
AB  - Presence of a small abdominal aortic aneurysm (AAA) often presents a difficult
      clinical dilemma--a reparative operation with its inherent risks versus
      monitoring the growth of the aneurysm, with the accompanying risk of rupture. The
      risk of rupture is conventionally believed to be a function of the AAA bulge
      diameter. In this work, we hypothesized that the risk of rupture depends on AAA
      shape. Because rupture is inevitably linked to stress, membrane theory was used
      to predict the stresses in the walls of an idealized AAA, using a model which was
      axisymmetric and fusiform, with the ends merged into straight opened-ended tubes.
      When the stresses for many different shapes of model AAAs were examined, a number
      of conclusions became evident: (i) maximum hoop stress typically exceeded maximum
      meridional stress by a factor of 2 to 3 (ii) the shape of an AAA had a small
      effect on the meridional stresses and a rather dramatic effect on the hoop
      stresses, (iii) maximum stress typically occurred near the inflection point of a
      curve drawn coincident with the AAA wall, and (iv) the maximum stress was a
      function--not of the bulge diameter---but of the curvatures (i.e. shape) of the
      AAA wall. This last result suggested that rupture probability should be based on
      wall curvatures, not on AAA bulge diameter. Because curvatures are not much
      harder to measure than bulge diameter, this concept may be useful in a clinical
      setting in order to improve prediction of the likelihood of AAA rupture.

PMID- 8872255
TI  - Bolus contaminant dispersion for oscillatory flow in a curved tube.
AB  - The dispersion of a bolus of soluble contaminant in a curved tube during volume
      cycled oscillatory flows is studied. Assuming a small value of delta (the ratio
      of tube radius to radius of curvature), the Navier-Stokes equations are solved by
      using a perturbation method. The convection-diffusion equation is then solved by
      expanding the local concentration in terms of the cross-sectionally averaged
      concentration and its axial derivatives. The time-averaged dimensionless
      effective diffusivity, <Deff/D>, is calculated for a range of Womersley number
      alpha and different values of stroke amplitude A and Schmidt number Sc, where D
      is the molecular diffusivity of contaminant. For the parameter values considered,
      the results show that axial dispersion in a curved tube is greater than that in a
      straight tube, and that it has a local maximum near alpha = 5 for given fixed
      values of Sc = 1, A = 5 and delta = 0.3. Finally, it is demonstrated how the time
      history of concentration at a fixed axial position can be used to determine the
      effective diffusivity.

PMID- 8872256
TI  - The conformity of a soft contact lens on the eye.
AB  - An axisymmetric elastic shell deformation model has been created to predict the
      conformity of a soft contact lens when pressed against the eye. Regions of
      contact and gap may be predicted, and the nonuniform reaction pressure between
      the lens and eye may also be found. This is important for issues like abrasion
      and comfort. Bending, membrane and transverse shear loads within the lens are
      also computed. Commercial soft contact lenses and a representative eye shape are
      used for the examples. We find that the uniformity of loading against the eye is
      strongly affected by the degree to which the lens is shaped to fit the eye, and
      relatively unaffected by the thickness of the lens.

PMID- 8872257
TI  - On the neuro-muscular control of trochlean joints.
AB  - This paper presents a simplified dynamical model for the control of one-degree-of
      freedom synovial joints considered as pure trochlean joints. This model considers
      the joint dynamics, the dynamics of the corresponding muscles and their calcium
      balance dynamics, as well as position and force feedbacks provided by the
      spindles and the Golgi tendon organs. Delays in the transmission of information
      are also taken into account as they proved to be of critical importance for the
      dynamical behavior of the considered systems. The linearized version of this
      model, which is valid for a rather wide range of movements, also allows us to
      investigate the stability of the system, as well as its stability robustness with
      respect to the feedback gains. Further, particular behaviors such as tremor are
      described.

PMID- 8872258
TI  - A model of fatigue and recovery in paraplegic's quadriceps muscle subjected to
      intermittent FES.
AB  - The objective of this paper was to propose a mathematical model for the fatigue
      and recovery phases of a paraplegic's quadriceps muscle subjected to intermittent
      functional electrical stimulation (FES). The model is based on in vivo,
      noninvasive, recording of fatigue related metabolic parameters recorded during
      stimulation and recovery. Records of the time variations of the muscle's
      phosphorus metabolites, particularly the phosphocreatine (PCr) and inorganic
      phosphorus (Pi), obtained from 31P magnetic resonance spectroscopy (MRS), were
      used to calculate the intracellular pH level in the muscle and this latter
      parameter was incorporated in a musculo-tendon model. The fatigue-recovery model
      allows the transition from the fatiguing phase to the recovery phase as soon as
      the stimulation terminates and vice versa. This model was incorporated into a
      Huxley type muscle model expressing the dynamics of the muscle. Two ordinary
      differential equations describing the musculo-tendon dynamics and the dynamics of
      the activation were solved simultaneously and records of the force trajectory
      during intermittent stimulations were obtained. Study cases ranging from 5 to 30
      s for each of the stimulation and recovery alternating phases were stimulated.
      The force and the total impulse in the modeled quadriceps muscle were computed.
      It was found that the greatest impulse was produced in intermittent stimulation
      of 40-50 s duty cycle, with a 50 percent ratio between the stimulation and
      recovery intervals. An additional series of six runs, including two contractions,
      one of 3 min and one of 1 min, separated by rest periods of 3, 6, 9, 12, 15, and
      30 min was performed. From the predicted force trajectories obtained, the maximal
      force values served for comparison with measured values made on one patient.

PMID- 8872259
TI  - A model of load sharing between muscles and soft tissues at the human knee during
      static tasks.
AB  - In this study, we have subjects voluntarily generate various forces in a
      transverse plane just above their ankles. The contributions of their muscles and
      soft tissues to the support of the total external knee joint moment were
      determined by analyzing the experimental data using a biomechanical model of the
      knee. In this model, muscle forces were estimated using the recorded EMGs. To
      account for subject variability, various muscle parameters were adjusted using a
      nonlinear least-squares fit of the model's estimated flexion and extension joint
      moments to those recorded externally. Using the estimated muscle forces, the
      contributions from the muscles and other soft tissues to the total joint moment
      were obtained. The results showed that muscles were primarily used to support
      flexion and extension loads at the knee, but in so doing, were able to support
      some part of the varus or valgus loads. However, soft tissue loading was still
      required. Soft tissues supported up to an average maximum of 83 percent of the
      external load in pure varus and valgus. Soft tissue loading in pure varus and
      valgus was less than 100 percent of the external load as the muscles, on average,
      were able to support 17 percent of the external load. This muscle support was by
      virtue of muscle cocontraction and/or specific muscle activation.

PMID- 8872260
TI  - Contact analysis of ultrahigh molecular weight polyethylene articular plate in
      artificial knee joint during gait movement.
AB  - To understand the wear mechanism of the ultrahigh molecular weight polyethylene
      (UHMWPE) articular plate used in artificial knee joints, the cyclic contact
      behavior of the plate during gait movement was analyzed using the constitutive
      equation for cyclic plasticity. In this study, two-dimensional plane strain model
      was employed and the contact behavior of femoral and tibial components was
      simulated by translating the contact stress distribution which was calculated
      from elasto-plastic indentation analysis of two components. For analytical model,
      the anatomical type artificial knee joint was employed and the effect of the
      shape of contact surface on the wear behavior of the plate was investigated. As a
      result, it was clarified that the wear of the plate should occur both from the
      surface and the subsurface of the plate and the wear behavior of the plate should
      be closely related with the shape of contact surface. Then the optimum shape of
      contact surface could be designed using this method.

PMID- 8872261
TI  - Automated finite element analysis of excised human femora based on precision 
      QCT.
AB  - The creation of 3-D finite element (FE) models of bone and implant-bone systems
      is a labor-intensive task due to the need to model different cases and
      variations, to perform patch tests and to account for the nonhomogeneous material
      properties with an acceptable amount of work. In this study, we developed an
      interface between a precision QCT and a FE system and applied it to a specimen
      bone. With the new method, the time necessary for model generation was reduced
      substantially. Furthermore, the elastic properties for each element were
      automatically derived from the corresponding CT-values. In order to demonstrate
      the importance of taking into account inhomogeneity, a comparison between the
      nonhomogeneous model and a homogeneous, "averaged" model was performed.

PMID- 8872262
TI  - Factors affecting the pullout strength of cancellous bone screws.
AB  - Screws placed into cancellous bone in orthopedic surgical applications, such as
      fixation of fractures of the femoral neck or the lumbar spine, can be subjected
      to high loads. Screw pullout is a possibility, especially if low density
      osteoporotic bone is encountered. The overall goal of this study was to determine
      how screw thread geometry, tapping, and cannulation affect the holding power of
      screws in cancellous bone and determine whether current designs achieve maximum
      purchase strength. Twelve types of commercially available cannulated and
      noncannulated cancellous bone screws were tested for pullout strength in rigid
      unicellular polyurethane foams of apparent densities and shear strengths within
      the range reported for human cancellous bone. The experimentally derived pullout
      strength was compared to a predicted shear failure force of the internal threads
      formed in the polyurethane foam. Screws embedded in porous materials pullout by
      shearing the internal threads in the porous material. Experimental pullout force
      was highly correlated to the predicted shear failure force (slope = 1.05, R2 =
      0.947) demonstrating that it is controlled by the major diameter of the screw,
      the length of engagement of the thread, the shear strength of the material into
      which the screw is embedded, and a thread shape factor (TSF) which accounts for
      screw thread depth and pitch. The average TSF for cannulated screws was 17
      percent lower than that of noncannulated cancellous screws, and the pullout force
      was correspondingly less. Increasing the TSF, a result of decreasing thread pitch
      or increasing thread depth, increases screw purchase strength in porous
      materials. Tapping was found to reduce pullout force by an average of 8 percent
      compared with nontapped holes (p = 0.0001). Tapping in porous materials decreases
      screw pullout strength because the removal of material by the tap enlarges hole
      volume by an average of 27 percent, in effect decreasing the depth and shear area
      of the internal threads in the porous material.

PMID- 8872263
TI  - Axisymmetric finite element analysis of a debonded total hip stem with an
      unsupported distal tip.
AB  - A tapered femoral total hip stem with a debonded stem-cement interface and an
      unsupported distal tip subjected to constant axial load was evaluated using two
      dimensional (2D) axisymmetric finite element analysis. The analysis was performed
      to test if the mechanical condition suggest that a "taper-lock" with a debonded
      viscoelastic bone cement might be an alternative approach to cement fixation of
      stem type cemented hip prosthesis. Effect of stem-cement interface conditions
      (bonded, debonded with and without friction) and viscoelastic response (creep and
      relaxation) of acrylic bone cement on cement mantle stresses and axial
      displacement of the stem was also investigated. Stem debonding with friction
      increased maximum cement von Mises stress by approximately 50 percent when
      compared to the bonded stem. Of the stress components in the cement mantle,
      radial stresses were compressive and hoop stresses were tensile and were
      indicative of mechanical taper-lock. Cement mantle stress, creep and stress
      relaxation and stem displacement increased with increasing load level and with
      decreasing stem-cement interface friction. Stress relaxation occur predominately
      in tensile hoop stress and decreased from 1 to 46 percent over the conditions
      considered. Stem displacement due to cement mantle creep ranged from 614 microns
      to 1.3 microns in 24 hours depending upon interface conditions and load level.

PMID- 8872264
TI  - Kinematics and dynamic stability of the locomotion of post-polio patients.
AB  - The study reported in this article was conducted to propose a set graphical and
      analytical tools and assess their clinical utility by analyzing gait kinematics
      and dynamics of polio survivors. Phase-plane portraits and first return maps were
      used as graphical tools to detect abnormal patterns in the sagittal kinematics of
      post-polio gait. Two new scalar measures were introduced to assess the bilateral
      kinematic symmetry and dynamic stability of human locomotion. Nine healthy
      subjects and seventeen post-polio patients were involved in the project.
      Significant increases in the knee extension and ankle plantar flexion of post
      polio patients were observed during the weight acceptance phases of their gait.
      Polio patients also exhibited highly noticeable excessive hip flexion during the
      swing phase of their ambulation. Using the proposed symmetry measure, we
      concluded that post-polio patients walked less symmetrically than normals. Our
      conclusion, however, was based on the bilateral symmetry in the sagittal plane
      only. Finally, we observed that post-polio patients walked significantly less
      stably than normals. In addition, weaknesses in lower extremity muscles of polio
      patients were found to be an important factor that affected stable ambulation.

PMID- 8872265
TI  - A parametric study of a side airbag system to meet deflection based criteria.
AB  - A side airbag system comprising of 12 liter bag to cover the BioSid chest and the
      abdomen down to the arm rest level, and 75 mm of padding to cover the
      pelvic/thigh area was evaluated by a series of sled tests at two different
      velocities, 10 m/s and 12 m/s. The initial bag (over) pressure was varied from 0
      to 80 kPa and the bag ventilation area was varied from zero to 1500 mm2.
      Compressed air was used to fill the bag. It was found that the ventilation of the
      bag reduced the maximum chest deflection by 30 percent and the maximum viscous
      criterion, VC, by 50 percent (comparison was made with the same bag without
      ventilation). A suitable initial bag (over) pressure was found to be about 50
      kPa, when the loading of the abdomen was also taken into consideration. The
      results indicate that the chest deflection is proportioned to the door average
      velocity (during the first 20 ms of deflection) to the power of about 2 and that
      the VC is proportional to the same velocity to the power of about 4. It was also
      found that a 12 liter ventilated side airbag resulted in 30-40 percent lower
      chest deflection and about 60 percent lower VC than 50 mm of chest padding
      (Ethafoam 220).

PMID- 8872266
TI  - Effect of uniaxial, cyclic stretch on the morphology of monocytes/macrophages in
      culture.

PMID- 8872267
TI  - A device for the measurement of pedicle screw moments by means of internal strain
      gauges.
AB  - Pedicle screws are commonly used in spinal reconstruction, and failure of pedicle
      screws due to bending is a significant clinical problem. To measure the moments
      typically placed on pedicle screws in situ we instrumented 7 mm Cotrel-Dubousset
      (CD) pedicle screws with internally mounted strain gauges. The screws were
      designed to measure flexion-extension moments at a single cross-section as
      dictated by strain gauge placement. It is possible to measure moments of up to 12
      Nm at any location along the length of the screw by constructing transducers with
      varying strain gauge placements. These transducers are capable of measuring
      moments at points located within the vertebra including the pedicle, which is
      where failure usually occurs clinically. Transducer output was both linear and
      reproducible. These transducers are being used to investigate the load transfer
      characteristics between the pedicle screw and the vertebra. This technique could
      be applied to investigations of load sharing in reconstruction plates, lag
      screws, and cross-locked intramedullary nails.

PMID- 8872268
TI  - Lumbar facet pain: biomechanics, neuroanatomy and neurophysiology.
AB  - Idiopathic low back pain has confounded health care practitioners for decades.
      Although there has been much advance in the understanding of the biomechanics of
      the lumbar spine over the past 25 years, the cellular and neural mechanisms that
      lead to facet pain are not well understood. An extensive series of experiments
      was undertaken to help elucidate these mechanisms and gain a better understanding
      of lumbar facet pain. Biomechanic and neuroanatomic studies were performed in
      human cadaveric facet joints and neurophysiologic studies were performed in New
      Zealand White rabbits. These studies provide the following evidence to help
      explain the mechanisms of lumbar facet pain: (1) The facet joint can carry a
      significant amount of the total compressive load on the spine when the human
      spine is hyperextended. (2) Extensive stretch of the human facet joint capsule
      occurs when the spine is in the physiologic range of extreme extension. (3) An
      extensive distribution of small nerve fibers and free and encapsulated nerve
      endings exists in the lumbar facet joint capsule, including nerves containing
      substance P, a putative neuromodulator of pain. (4) Low and high threshold
      mechanoreceptors fire when the facet joint capsule is stretched or is subject to
      localized compressive forces. (5) Sensitization and excitation of nerves in facet
      joint and surrounding muscle occur when the joint is inflamed or exposed to
      certain chemicals that are released during injury and inflammation. (6) Marked
      reduction in nerve activity occurs in facet tissue injected with hydrocortisone
      and lidocaine. Thus, the facet joint is a heavily innervated area that is subject
      to high stress and strain. The resulting tissue damage or inflammation is likely
      to cause release of chemicals irritating to the nerve endings in these joints,
      resulting in low back pain.

PMID- 8872269
TI  - Elongation mechanism of collagen fibrils and force-strain relations of tendon at
      each level of structural hierarchy.
AB  - Tension-induced structural changes in bovine Achilles tendon collagen at each
      level of the hierarchy structure were investigated by means of the X-ray
      diffraction method. In order to estimate the straining mechanism in a collagen
      fibril, three elementary models for molecular elongation and rearrangement of
      collagen fibril were proposed on the basis of the Hodge-Petruska model: [1]
      molecular elongation, [2] increase in gap region and [3] relative slippage of
      laterally adjoining molecules. The characteristic 67 nm D-period of a collagen
      fibril increases with applied force. A Hookean-type force-strain curve was
      obtained for the D-period while the force-strain relation for the tendon was non
      Hookean. The relative intensity of third-order reflection of the D-period to that
      of the second-order one, I3/I2, decreased with the applied force. This decrease
      in I3/I2 indicates a decrease in the ratio of the overlap region of collagen
      fibril to the D-period, O/D, which was analyzed on the basis of the Hodge
      Petruska model. Decomposition of the observed strain in the D-period, epsilon(D),
      into these three deforming modes revealed that the major contribution to
      epsilon(D) originated from mode [1], molecular elongation. It was deduced that a
      fibril is mechanically composed of molecules connected serially to each other.

PMID- 8872270
TI  - A simulation study of vertical jumping from different starting postures.
AB  - This paper addresses the question of whether maximal vertical jump height depends
      on initial jumping posture. A direct dynamics computer simulation approach was
      used to avoid subject preference and practice effects. The human body was modeled
      as four rigid segments connected by ideal hinge joints, with movement constrained
      to the sagittal plane and driven by three single-joint torque actuators. Maximal
      height jumps were found for each of 125 different initial postures. For each
      initial posture, the optimal pattern of joint torque actuator onset times was
      found using a multidimensional simplex algorithm searching for maximal jump
      height. The model results revealed that maximal jump height is relatively
      insensitive to initial posture, but that the pattern of joint torque onset times
      necessary to effect these optimal heights varies considerably. Model kinematics
      indicate that the variability in onset times is necessary to allow the body to re
      orient itself in different ways during the downward countermovement phase. This
      variable re-orientation strategy is followed by a more stereotyped upward thrust
      phase that is similar despite the differences in starting postures. Model center
      of mass, joint and segmental kinematics show many features found in experimental
      studies of jumping, despite the exclusive use of single torque actuators.
      However, a proximal-to-distal sequence of joint coordination was not found,
      possibly because of the omission of antagonist and bi-articular muscles. The
      results suggest that similar vertical jump heights should be obtained using a
      wide range of initial starting positions.

PMID- 8872271
TI  - Contractile behaviour in skeletal muscle-tendon unit during small amplitude sine
      wave perturbations.
AB  - The effects of sinusoidal vibrations (0.2 mm) on contractile behaviour of the
      medial gastrocnemius muscle of the rat (N = 6) were determined over a wide range
      of frequencies (10-210 Hz). The performance of the contractile element (CE)
      during maximal tetanic contractions and vibrations was calculated by correcting
      muscle performance for series elasticity. For one experimental muscle the
      contractions were simulated using a computer model based on mechanical
      characteristics of that particular muscle. It was found that 10 Hz movements
      increased the slope of the CE force-velocity curve, compared to its
      isokinetically determined characteristics. At higher frequencies (30 Hz and
      above) this slope decreased. It is hypothesised that these two changes in CE
      behaviour are based on the same phenomena in CE behaviour: force enhancement by
      active stretch and depression by shortening. The time constants of the decay of
      these processes may cause the different impact on CE force-velocity behaviour. It
      is concluded that CE performance is affected at all frequencies, but its impact
      on muscle-tendon performance shows at low frequencies only. At high-frequencies
      series elastic characteristics play a dominant role.

PMID- 8872272
TI  - Biomechanical model of the human knee evaluated by neuromuscular stimulation.
AB  - A detailed model of the human knee was developed to predict shank motion induced
      by functional neuromuscular stimulation (FNS). A discrete-time model is used to
      characterize the relationship between stimulus parameters and muscle activation.
      A Hill-based model of the musculotendon actuator accounts for nonlinear static
      and dynamic properties of both muscle and tendon. Muscle fatigue and passive
      muscle viscosity are modeled in detail. Moment arms are computed from
      musculotendon paths of 13 actuators and from joint geometry. The model also takes
      nonlinear body-segmental dynamics into consideration. The simulated motion is
      visualized by graphic animation. Individual model parameters were identified by
      specific procedures such as anthropometric measurements, a passive pendulum test,
      and specific open-loop stimulation experiments. Model results were compared with
      experimental data obtained by stimulating the quadriceps muscle of paraplegic
      patients with surface electrodes. The knee moment, under isometric conditions,
      and the knee angle, under conditions of freely swinging shank, were measured. In
      view of the good correspondence obtained between model predictions and
      experimental data, we conclude that a biomechanical model of human motion induced
      by FNS can be used as a mathematical tool to support and accelerate the
      development of neural prostheses.

PMID- 8872273
TI  - Converse piezoelectric effect detected in fresh cow femur bone.
AB  - A piezoelectric effect has been reported to exist in biological tissues, in
      particular in dry bone. Since the precision and resolution now obtainable are
      much greater, we decided to verify the presence of the converse effect
      (dimensional change under the application of an electric field) in fresh bone
      samples, by using a very high sensitivity instrument. We took, in varying
      orientations, five fresh femur cylindrical bone specimens from a cow leg and
      placed them as a single piece, or as a stack of 10 thin interlayered slices from
      one specimen to improve sensitivity, in a special microwave double cavity
      differential dilatometer. The thickness of the specimen was approximately 10mm.
      The applied field strength for the nonstacked specimen was near 10 kV m-1.
      Thickness variation was measured along and across the electric field lines. We
      applied the electric field as a switched polarity square wave. This allows the
      thermal dilution of specimen warming and possible electrostriction effects, which
      are insensitive to the direction of the applied field, to be separated from an
      electromechanical effect which is sensitive to direction. Using coherent signal
      averaging over approximately 600 cycles to combat instrumental noise we observed
      nonthermal, nonelectrostrictional thickness variations in all samples. The
      amplitudes we observed were near 3 pm for the 1 cm nonstacked specimen, and the
      bone's responses to electric fields ranged from 26 to 38 fm V-1. With response
      magnitudes approximating those predicted theoretically for the converse
      piezoelectric effect in bone we conclude that the piezoelectric theory could not
      be falsified with our experiments.

PMID- 8872274
TI  - Effects of walking velocity on relative phase dynamics in the trunk in human
      walking.
AB  - The nature of coordination changes and stability features in the relative phase
      dynamics of the trunk were examined in seven healthy subjects, while walking
      velocity on a treadmill was gradually increased and decreased. Predictions from
      Schoner et al (J. Theor. Biol. 142, 359-391, 1990) regarding transition
      mechanisms in quadrupedal walking generalized to pelvis-thorax phase relations in
      bipedal walking, in that more continuous transitions with and without loss of
      stability were observed when walking velocity was manipulated as a control
      parameter. Relative phase changed from more in-phase (about 25 degrees) at lower
      velocities to more out-of-phase (about 110 degrees) at higher velocities.
      Stability analysis of relative phase demonstrated the existence of more than one
      stable coordination pattern ('multistability'). Total ranges of motion in pelvis,
      thorax, and trunk, as well as stride length were larger at the decreasing
      velocity range was compared to the increasing velocity range, showing dependence
      on direction of control parameter manipulation ('hysteresis effect'). The nature
      of these transitions identifies phase relations in the trunk in human walking as
      lower symmetry dynamics, a finding consistent with the proposed dynamics of the
      quadrupedal walking mode. These results suggest the existence of different
      coordination patterns (multistability) in the human bipedal walking mode and
      question traditional distinctions in only two modes (walking and running) in
      human gait.

PMID- 8872275
TI  - Variability of femoral muscle attachments.
AB  - Analytical and experimental models of the musculoskeletal system often assume
      single values rather than ranges for anatomical input parameters. The hypothesis
      of the present study was that anatomical variability significantly influences the
      results of biomechanical analyses, specifically regarding the moment arms of the
      various thigh muscles. Insertions and origins of muscles crossing or attaching to
      the femur were digitized in six specimens. Muscle volumes were measured; muscle
      attachment area and centroid location were computed. To demonstrate the influence
      of inter-individual anatomic variability on a mechanical modeling parameter, the
      corresponding range of muscle moment arms were calculated. Standard deviations,
      as a percentage of the mean, were about 70% for attachment area and 80% for
      muscle volume and attachment centroid location. The resulting moment arms of the
      m. gluteus maximus and m. rectus femoris were especially sensitive to anatomical
      variations (SD 65%). The results indicate that sensitivity to anatomical
      variations should be analyzed in any investigation simulating musculoskeletal
      interactions. To avoid misinterpretations, investigators should consider using
      several anatomical configurations rather than relying on a mean data set.

PMID- 8872276
TI  - Calcium buffering is required to maintain bone stiffness in saline solution.
AB  - This work determined whether mineral dissolution due to prolonged testing or
      storage of bone specimens in normal saline would alter their elastic modulus. In
      one experiment, small pieces of equine third metacarpal bone were soaked in
      normal saline supplemented with varying amounts of CaCl2. Changing Ca ion
      concentrations in the bath were monitored and the equilibrium concentration was
      determined. In a second experiment, the elastic moduli of twenty 4 x 10 x 100 mm
      equine third metacarpal beams were determined non-destructively in four-point
      bending. Half the beams were then soaked for 10 days in normal saline, and the
      other half in saline buffered to the bone mineral equilibrium point with Ca ions.
      Modulus measurements were repeated at 6 and 10 days. The equilibrium Ca ion
      concentration for bone specimens was found to be 57.5 mg l-1. The modulus of bone
      specimens soaked in normal saline significantly diminished 2.4%, whereas the
      modulus of those soaked in calcium-buffered saline did not change significantly.

PMID- 8872277
TI  - Determination of the step duration of gait initiation using a mechanical energy
      analysis.
AB  - The analysis of gait initiation (the transient state between standing and
      walking) is an important diagnostic tool in the study of pathologic gait and the
      evaluation of prosthetic devices. Therefore it is important to know the step
      duration of gait initiation. However, there is little agreement in the literature
      regarding this step duration, since each author has based their conclusion on a
      different biomechanical parameter. In this study, gait initiation in seven normal
      subjects was studied using a mechanical energy analysis. The number of steps
      necessary to reach steady state was determined based on the fact that in steady
      state gait, the net mechanical work of the body over one stride is zero (Winter
      et al. J. Biomechanics 9, 253-257, 1976). The variance of the work for a stride
      during steady-state walking was calculated for 100 steady-state trials from a
      separate database of normal subjects. The stride work was normalized to the
      subject's body weight (BW) and leg length (LL), and 95% confidence limits were
      defined from this data at -1.68%BW * LL < epsilon < 1.28%BW * LL. Total body
      energy during gait initiation was then computed for the seven test subjects. The
      energy analysis of gait initiation showed that steady state was attained by the
      end of three full steps. Therefore, a researcher studying gait initiation must
      allow his/her subject to take three full steps when recording data to ensure that
      the full event is included.

PMID- 8872278
TI  - Experimental evaluation of theoretical contact forces in the cat patellofemoral
      joint.
AB  - The purpose of this study was to evaluate the accuracy of patellofemoral contact
      forces predicted from a planar model of the patella by comparison with
      experimentally determined in situ contact forces. Patellofemoral contact
      pressures and areas were measured experimentally in an animal preparation with
      pressure sensitive film. Patellar tendon forces and lines of action used as input
      to the model were measured in the intact joint of the same preparation. Predicted
      and measured contact forces at different joint loads were compared at three
      different joint angles using linear regression analysis. r2-coefficients ranged
      from 0.94 to 0.95, and the slopes of the regression lines ranged from 1.64 to
      2.11 for the three joint angles. The high r2-coefficients for all comparisons
      indicate that both methods were able to quantify the relative changes in the cat
      patellofemoral contact forces under different loading conditions accurately.
      However, the consistent finding of slopes greater than 1.0 indicates that the
      measured contact forces were systematically larger than the corresponding
      predicted forces. Analysis of the possible sources for the observed discrepancies
      between predicted and measured contact forces suggested that the directly
      measured patellar tendon forces were the most likely candidate causing the
      systematic differences. The results of this study suggest that a relatively
      simple model of the patellofemoral joint appears to be valid to quantify joint
      contact forces if appropriate patellar tendon force values can be provided as
      input to the model.

PMID- 8872279
TI  - Cross-sectional area measurement of soft tissue. A new casting method.
AB  - A new replica moulding technique for determining cross-sectional area has been
      developed. The accuracy of this technique has been investigated. Comparisons have
      been made with the area micrometer and the laser micrometer to establish the
      relative accuracy of each technique. The replica technique systematically
      underestimated the cross-sectional area by 6.2%. However, when this shrinkage
      artefact was corrected for, the residual error was +/- 1.8%. Relative to the
      corrected replica method, it was calculated that the area micrometer
      underestimated cross-sectional area by 16.2 +/- 6.9% (SD) and that the assumption
      of a convex cross-section would have caused the laser micrometer to overestimate
      cross-sectional area by an average of 2.3 +/- 1.5% (SD) for tendon, 4.7 +/- 2.5%
      for 'round' ligament specimens and 19.1 +/- 6.4% for cruciate ligament bundles
      with obvious concavities in their cross-sections. The moulding method was thought
      to be particularly useful for soft tissue specimens with irregular cross
      sections.

PMID- 8872280
TI  - Classification of errors in locating a rigid body.
AB  - This paper discusses the manner in which random Gaussian errors affect the
      determination of body segment kinematics. For the process of modelling rigid body
      (RB) motion, three types of kinematic errors, input, measured and theoretical,
      are identified. These correspond to errors in: the determination of three
      dimensional observed points, the RB fit of those points, and the estimation of
      true RB positions, respectively. Of these, the theoretical error is most critical
      and most pivotal. Accuracy is provided when the theoretical error is minimised,
      yet only the measured error can be minimised by RB modelling algorithms. In
      computer simulations one may determine the effect that such manipulations have on
      theoretical error, yet in most experimental conditions this value may not even be
      calculated. Fortunately, computer simulations can be performed to determine the
      inter-relationships between types of RB modelling errors. Such simulations can
      also be used to investigate the effects of RB shape. In this paper, Monte Carlo
      simulations were performed on three unit radius RBs; a triangle, a square and a
      tetrahedron. Although the use of the triangle provided the lowest measured error,
      this also coincided with the greatest theoretical error. The use of redundant
      points was found to yield superior theoretical accuracies. A slight advantage was
      gained with use of the non-planar point arrangement on the tetrahedron, both the
      measured and theoretical errors were reduced. Finally, the superiority of RB
      modelling over individual point tracking was reflected in all of the results;
      between 33 and 50% of the input error was eliminated with the use of RB
      modelling.

PMID- 8872281
TI  - A method for measuring external loads during dynamic lifting exertions.
AB  - Biomechanical analyses of lifting exertions often require measured values of
      applied trunk moments and forces as baseline or validation data. Accurate
      measures of the trunk kinetic data are difficult to achieve from dynamic
      exertions without significant approximation, cost, or motion constraints. The
      purpose of this effort was to develop and validate a means to directly measure
      multi-dimensional, trunk moments which occur during dynamic lifting exertions.
      Force plate reaction loads coupled through a lower-body isolation structure
      designed to fasten the hips and legs into a known static position, were employed
      to compute the moment vectors about the lumbar spine. Results demonstrate the
      applied moments about the lumbo-sacral junction of the spine can be accurately
      measured from a single force plate, allowing biomechanical evaluation of dynamic
      lifting exertions without constraining the motions of the upper body.

PMID- 8872282
TI  - Adjustments to Zatsiorsky-Seluyanov's segment inertia parameters.
AB  - Zatsiorsky et al. (in Contemporary Problems in Biomechanics, pp. 272-291, CRC
      Press, Massachusetts, 1990a) obtained, by means of a gamma-ray scanning
      technique, the relative body segment masses, center of mass (CM) positions, and
      radii of gyration for samples of college-aged Caucasian males and females.
      Although these data are the only available and comprehensive set of inertial
      parameters regarding young adult Caucasians, they have been rarely utilized for
      biomechanical analyses of subjects belonging to the same or a similar population.
      The main reason is probably that Zatsiorsky et al. used bony landmarks as
      reference points for locating segment CMs and defining segment lengths. Some of
      these landmarks were markedly distant from the joint centers currently used by
      most researchers as reference points. The purpose of this study was to adjust the
      mean relative CM positions and radii of gyration reported by Zatsiorsky et al.,
      in order to reference them to the joint centers or other commonly used landmarks,
      rather than the original landmarks. The adjustments were based on a number of
      carefully selected sources of anthropometric data.

PMID- 8872283
TI  - Joint center longitudinal positions computed from a selected subset of Chandler's
      data.
AB  - Mathematical models of the human body are indispensable tools for studying the
      biomechanics of human movement. The geometrical centers of the 12 main joints
      (shoulders, elbows, wrists, hips, knees ankles), modeled as simple mechanical
      joints, are widely used as reference points for building mathematical models of
      the human body. These reference points, typically defined as "joint centers", are
      assumed to maintain a fixed 3D position relative to both the segments forming the
      joint, throughout the range of joint motion. No single point in a human joint
      perfectly meets this assumption, and no simple method is available for locating
      the points that are closest to meet it. Researchers often have recourse to
      subjective methods, based on their knowledge of anatomy. Objective estimates are
      easily attainable if the positions of a few bony landmarks can be measured on the
      subject, and the longitudinal distances of the joint centers from these landmarks
      are known. A subset of the anthropometric measurements performed by Chandler et
      al. (NTIS No. AD 710-622, 1975) on six cadavers was critically selected and
      utilized to compute the percent longitudinal distances of the 12 main joint
      centers from neighboring bony landmarks, relative to the lengths of the
      respective proximal and/or distal segments. Three-dimensional positions are
      attainable as well, by assuming joint centers lay on the respective segment
      longitudinal axes. The use of a method for accurately locating joint centers is
      recommended, particularly when they are used as reference points for defining a
      personalized geometrical model of a subject's body.

PMID- 8872284
TI  - Force-length properties in stable skeletal muscle fibers--theoretical
      considerations.
AB  - Differences in the force-length (F-L) properties between sarcomeres and fibers
      have been associated with the supposed unstable nature of the sarcomere F-L
      relation on the descending limb (i.e. at sarcomere lengths greater than optimal
      length). Recently, it has been suggested that sarcomere behavior in a fiber is
      stable during contractions on the descending limb of the F-L relation; therefore,
      a factor other than sarcomere instability must be responsible for the observed
      differences in the F-L relations of sarcomeres and fibers. The purpose of this
      study was to determine theoretically the F-L relation of a muscle fiber when
      sarcomeres were at a stable, steady-state length. Three models of muscle fibers
      are presented; each model contains sarcomeres with different mechanical
      properties which have been observed experimentally. Results of these theoretical
      considerations demonstrate that sarcomeres with the classic F-L properties as
      measured by Gordon et al. (J. Physiol. 184, 170-192, 1966) cannot predict the F-L
      relation exhibited by fibers. The addition of cross-bridge stiffness properties
      to the classic sarcomere F-L relation still does not explain the differences
      between the sarcomere and fiber F-L relations. However, if history dependent
      sarcomere properties are used, the fiber F-L relation exhibits an elongated
      plateau and greater forces on the descending limb compared to the classic
      sarcomere F-L relation; and the fiber F-L relation corresponds qualitatively to
      experimental findings.

PMID- 8872285
TI  - The 'standardized femur program' proposal for a reference geometry to be used for
      the creation of finite element models of the femur.

PMID- 8872286
TI  - A review of "heart healthy" cookbooks.

PMID- 8872287
TI  - The future of cardiovascular medicine. An opportunity for prevention and
      rehabilitation.

PMID- 8872288
TI  - Training level comparison study. Effect of high and low intensity exercise on
      ventilatory threshold in men with coronary artery disease.
AB  - PURPOSE: To determine whether exercise at low intensity (LO; 50% of peak VO2) or
      high intensity (HI; 85% of peak VO2) results in improvement of the ventilatory
      threshold (VT), 186 men with coronary artery disease (CAD) were enrolled in an
      exercise study for 1 year. METHODS: A symptom-limited exercise test was performed
      at baseline and the heart rate corresponding to 50% and 85% of peak VO2 was
      determined. Subjects were randomized to LO or HI intensity exercise. Exercise
      sessions included 45 minutes of walking/jogging and/or stationary cycling at the
      appropriate target heart rate and were conducted 3 days per week. The exercise
      test was repeated at 3 and 6 months. Target heart rates were revised to adjust
      for training. RESULTS: Both LO and HI resulted in improved VO2 at VT and peak.
      However, HI resulted in greater improvement than LO. CONCLUSION: Among this
      population, both HI and LO improve the VO2 at VT and peak, but the improvement is
      greater with HI. The VT can be a useful adjunct to heart rate and peak oxygen
      uptake when prescribing exercise.

PMID- 8872289
TI  - Supervised exercise and electrocardiographic monitoring during cardiac
      rehabilitation. Impact on patient care.
AB  - PURPOSE: To determine the frequency of medical problem detection during
      supervised cardiac rehabilitation exercise, and to assess its impact on patient
      care alteration. METHODS: Six hundred sixty-six cardiac participants (388 in
      Phase II and 278 in Phase III) were studied during a 1-year period (1989-1990).
      The supervisory staff recorded all phone calls made to referring physicians
      regarding individual patient problems identified during exercise sessions
      including subsequent alteration in patient care. RESULTS: Overall, 112 of 666
      (17%) of the patients had problems detected that prompted calls to referring
      physicians. There was 0.009 call per patient exercise hour, compared to 0.002
      call per patient exercise hour in the Phase II and Phase III patients,
      respectively, P = .0001. Although Phase II patients had a higher uncorrected
      arrhythmia call frequency compared to the Phase III patients, arrhythmia call
      frequency was higher in Phase III patients, when corrected for the number of
      monitored exercise hours (P = .02). Fifty-five percent of calls resulted in
      patient care alteration, and telemetry-related calls and nontelemetry-related
      calls resulted in a similar proportion of patient care alteration. Overall, 11%
      (73 of 666) of patients had alteration of their care, of which 4% (24 of 666)
      resulted from telemetry-related calls. Clinical variables between the patients
      with calls versus the patients with no calls demonstrated that the call group
      were older, and had a more frequent history of hypertension. CONCLUSION:
      Medically supervised cardiac rehabilitation with and without telemetry monitoring
      detects problems that lead to alteration in medical care. Older patients have
      more problems detected. Medical problem detection may contribute to the
      beneficial impact of cardiac rehabilitation observed in randomized trials.

PMID- 8872290
TI  - Prediction of oxygen uptake and energy expenditure during exercise in obese
      women.
AB  - PURPOSE: For patients concerned with weight loss, monitoring the energy balance
      between daily dietary intake and exercise expenditure can be useful. Formulas
      commonly used to estimate the energy costs of exercise were previously derived
      from healthy men of normal body weight. The purpose of this study was to
      determine the relationship between measured and predicted exercise energy
      expenditure for obese women. METHODS: Oxygen uptake (VO2) was measured using
      respiratory gas analysis in 45 obese (92 +/- 16 kg; 40 +/- 7% fat) and 10 normal
      weight (control) (58 +/- 5 kg; 21 +/- 6% fat) women during progressive exercise
      on a motorized treadmill. VO2 was also calculated at matched workrates using a
      regression equation published by the American College of Sports Medicine. The
      relationship between predicted versus measured VO2 was determined using least
      squares regression analysis. RESULTS: The slope of the regression line for
      measured versus predicted VO2 for controls (y = 0.98x +/- 0.56; P < .001) was
      different than that of obese women (y = 0.75x +/- 3.06; P < .001). The slope of
      the regression line for controls was in close approximation to the line of
      identity, whereas the slope for obese was below it. Using VO2 to calculate kcal,
      measured energy expenditure, was significantly lower than predicted energy
      expenditure for obese subjects, but not for controls at several matched
      workrates: Stage III (213 +/- 40 versus 225 +/- 38 kcal per 30 minutes, P <
      .001); stage 4 (292 +/- 55 versus 340 +/- 58 kcal per 30 minutes, P < .001); and
      stage 5 (330 +/- 55 versus 412 +/- 70 kcal per 30 minutes, P < .001) obese
      measured versus obese predicted, respectively. CONCLUSIONS: The authors conclude
      that the standard prediction equation gives a better estimation of VO2 for women
      who have average body weight and body fat than for obese women. This may, in
      part, be due to the differences in weight and/or fat mass between these subjects
      and those used to derive this equation. These findings should be considered when
      estimates of VO2 and energy expenditure are used rather than direct measures for
      obese women.

PMID- 8872291
TI  - Acute responses to using walking poles in patients with coronary artery disease.
AB  - PURPOSE: This study was designed to assess the safety and effectiveness of
      walking when using 1-lb walking poles in Phase III/IV cardiac rehabilitation
      patients. METHODS: Following instruction on the proper use of the poles and
      adequate time to practice, each subject completed two 8-minute walking trials on
      a level treadmill either with or without walking poles. Each trial was conducted
      at an identical speed for each subject in a randomized order. Heart rate (HR),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), and ratings of
      perceived exertion (RPE) were recorded every 2 minutes during each trial, while
      ECG responses (ST segment changes and dysrhythmias) were monitored continuously.
      RESULTS: Walking with poles significantly (P < .05) increased the energy cost of
      walking by 21% (3.8 mL/kg/min) compared to walking without poles. There were also
      significant (P < .05) increases in HR (14 bpm), SBP (16 mm Hg), and DBP (4 mm Hg)
      when comparing conditions. Calculated oxygen pulse (mL O2.heart beat) values
      indicated that changes in HR were consistent with the increase in VO2 and were
      not related to a pressor response mechanism. The only dysrhythmias noted were
      isolated PVCs, with no differences in the frequency of occurrence between trials.
      There were no adverse ST segment changes with either trial. CONCLUSIONS: These
      data demonstrate that at a given speed, the use of 1-lb walking poles can safely
      increase the intensity of walking exercise in Phase III/IV cardiac rehabilitation
      patients.

PMID- 8872292
TI  - Effect of hemoglobin on the oxygen uptake of patients with coronary artery
      disease.
AB  - BACKGROUND: Oxygen uptake (VO2) is frequently measured or predicted in patients
      referred to cardiac rehabilitation programs to quantify functional capacity and
      prescribe exercise. When entering Phase II programs, some patients are in an
      anemic state that normalizes over the course of the program. The purpose of this
      study was to evaluate the relationship between the change in hemoglobin levels
      and the change in VO2 in a group of Phase II cardiac rehabilitation patients.
      METHODS: Sixty-six cardiac patients (45 men and 21 women) underwent a graded
      exercise test with the collection of expired air before and following
      participation in a Phase II cardiac rehabilitation program. Blood was sampled
      before each test for hemoglobin-hematocrit analysis. The change in absolute VO2
      over the course of the rehabilitation program was chosen as the response variable
      in a simple regression model designed to measure the effect of normalization of
      hemoglobin levels during that period. RESULTS: A simple regression of the change
      in absolute VO2 on patient age and the changes in hemoglobin concentration and
      maximal work rate produced coefficient estimates that are statistically
      significant and have the signs one would expect. A bootstrap re-estimation of the
      regression model gives essentially the same coefficients and supports the results
      of the simple model. CONCLUSIONS: These results indicate that low levels of
      hemoglobin concentration adversely affect the VO2 of patients with cardiac
      disease and should be accounted for when assessing functional capacity. This may
      be even more critical when estimating rather than measuring VO2. Finally,
      absolute VO2 may not be the best measure of functional capacity. A submaximal
      marker, such as the VO2 at the ventilatory threshold, may be a more useful
      response variable.

PMID- 8872293
TI  - Do we need new antihypertensive drugs?

PMID- 8872294
TI  - From alpha and beta to I1: an overview of sympathetic receptors involved in blood
      pressure control targets for drug treatment.
AB  - There is no doubt that the sympathetic nervous system (SNS) plays an important
      role in the pathogenesis and maintenance of hypertensive disease, although many
      details concerning this association remain to be clarified. Over the years,
      several types of antihypertensive drugs have been developed that can impair SNS
      activity at virtually all levels of the system. Alpha and beta-adrenoceptor
      antagonists, postganglionic sympathetic neuron blockers and ganglioplegic agents
      are well-known examples of drugs with a predominantly peripheral activity. The
      CNS regulation of peripheral sympathetic activity offers a further possibility to
      counteract the influence of SNS activity. In particular, central
      catecholaminergic neurons and alpha-adrenoceptors have been analyzed in detail
      and are recognized as important targets for the classic centrally acting
      antihypertensives clonidine, guanfacine, and alpha-methyldopa. Initially, these
      drugs were assumed to reduce elevated blood pressure via the stimulation of
      central alpha-adrenoceptors in the brainstem, thus leading to peripheral
      sympathoinhibition and a reduction of elevated blood pressure, heart rate, and
      plasma catecholamines. In a later stage it has been recognized that central
      imidazoline (I1) receptors may also be involved in the central regulation of
      peripheral sympathetic activity and that they act as a target for centrally
      acting antihypertensives. Moxonidine and rilmenidine are the prototypes of such
      agents. Accordingly, the receptor profile of the various types of centrally
      acting antihypertensives can be characterized as follows: alpha-methyl-DOPA
      (through alpha-methyl-norepinephrine) alpha 2; clonidine (mixed agonist), alpha 2
      + I1; moxonidine, rilmenidine, I1 > alpha 2. The various compounds mentioned will
      thus cause peripheral sympathoinhibition, initiated by different receptor targets
      in the CNS. Because most of the adverse reactions to clonidine and related drugs
      are mediated by central alpha-adrenoceptors, is is hoped that the imidazoline
      receptor agonists (moxonidine, rilmenidine) will show a more favorable pattern of
      side effects.

PMID- 8872295
TI  - Neurons and receptors in the rostroventrolateral medulla mediating the
      antihypertensive actions of drugs acting at imidazoline receptors.
AB  - A group of clinically useful antihypertensive agents, including clonidine,
      moxonidine, and rilmenidine, are all ligands at alpha(2)-adrenergic and
      imidazoline (I-) receptors, the latter principally of the I1-subclass. These
      agents all lower blood pressure by reducing the activity of tonically active
      sympathoexcitatory reticulospinal neurons of the C1 area of the
      rostroventrolateral medulla (RVL). They tonically excite preganglionic
      sympathetic neurons in the spinal cord by release of L-glutamate and mediate most
      reflexes influencing blood pressure. The RVL contains alpha(2)-adrenergic and I1
      receptors, and there is evidence to suggest that both receptors may participate
      in the hypotensive actions of the drugs. However, because only activation of the
      alpha(2)-adrenergic receptors appears responsible for somnolence, the imidazoline
      receptor agonists moxonidine and rilmenidine, both relatively selective for I
      receptors, may have superior clinical utility in antihypertensive therapy, since
      they are sympatholytic and also suppress the generation of angiotensin II.

PMID- 8872296
TI  - Antihypertensive therapy and renal function.
AB  - Although renal abnormalities may be present in patients with untreated, newly
      diagnosed essential hypertension, predictors of the development of progressive
      renal failure are of great concern. In addition, unanswered questions are the
      final arterial pressure achieved during treatment as well as the ideal renal- and
      cardiovascular-protective drug therapy. Most antihypertensive agents given for
      periods of several months in monotherapy have no consistent effect on renal
      function and hemodynamics. However, they may differ with regard to their
      influence on other factors considered to be markers of significant impact of
      hypertension on the kidney, such as albuminuria. Studies of very long-term
      therapy on the evolution of renal function and using reliable indicators of the
      variation of glomerular filtration rate are needed.

PMID- 8872297
TI  - Pharmacology of moxonidine, an I1-imidazoline receptor agonist.
AB  - Moxonidine is a second-generation, centrally acting antihypertensive drug with a
      distinctive mode of action. Moxonidine activates I1-imidazoline receptors (I1
      receptors) in the rostroventrolateral medulla (RVLM), thereby reducing the
      activity of the sympathetic nervous system. Moxonidine leads to a pronounced and
      long-lasting blood pressure reduction in different animal models of hypertension,
      e.g., spontaneously hypertensive rats, renal hypertensive rats, and renal
      hypertensive dogs. Blood pressure reduction with moxonidine is usually
      accompanied by a reduction in heart rate which, however, in most studies is of
      shorter duration and lesser magnitude than the fall in blood pressure. Chronic
      administration of moxonidine to SHRs with established hypertension causes
      normalization of myocardial fibrosis, capillarization, and regressive changes in
      myocytes, in parallel with the reduction of blood pressure. Left ventricular
      hypertrophy and renal glomerulosclerosis are also significantly reduced. After
      withdrawal of chronic moxonidine treatment, blood pressure gradually rises to
      pretreatment values. Direct injection of moxonidine into the vertebral artery of
      cats elicits a more pronounced fall in blood pressure compared with i.v.
      injection of an equivalent dose. This observation and others clearly indicate
      that moxonidine's antihypertensive activity is centrally mediated. The RVLM is
      the site of action within the CNS that mediates pronounced blood pressure
      reduction after direct administration of moxonidine into the RVLM of anesthetized
      SHRs. Selective I1-receptor antagonists introduced into this area abolish the
      action of systemic moxonidine. Receptor binding studies have shown high and
      selective affinity of moxonidine for I1-receptors vs. alpha(2)-adrenergic
      receptors. In vivo studies using a variety of selective I1 or alpha(2)-adrenergic
      agonists and antagonists have confirmed the primary role of I1-receptors in blood
      pressure regulation by moxonidine. In addition to lowering blood pressure,
      moxonidine possesses further properties that appear likely to be relevant in its
      therapeutic application in the hypertensive syndrome. Moxonidine increases urine
      flow rate and sodium excretion after central and direct intrarenal
      administration. It is active against ventricular arrhythmias in a variety of
      experimental settings. It lacks the respiratory depressant effect attributed to
      central alpha 2 activation. It exerts beneficial effects on glucose metabolism
      and blood lipids in genetically hypertensive obese rats. It exhibits anti-ulcer
      activity. And, finally, moxonidine lowers intraocular pressure, suggesting a
      possible benefit in glaucoma. Therefore, moxonidine, by its novel mode of action,
      represents a new therapeutic principle in the treatment of hypertension. Because
      of its unique profile, moxonidine may prove to be effective in slowing
      progression of the disease by providing protective effects beyond merely blood
      pressure reduction. Further studies are needed to verify this potential.

PMID- 8872298
TI  - Effective antihypertensive therapy: blood pressure control with moxonidine.
AB  - Stimulation of the imidazoline I1-receptor represents a new mode of
      antihypertensive action, inhibiting peripheral alpha-adrenergic tone by a central
      mechanism. Moxonidine is an imidazoline I1-receptor modulator. Acute hemodynamic
      studies indicate that moxonidine results in an acute fall of both blood pressure
      and systemic vascular resistance, whereas heart rate, cardiac output, stroke
      volume, and pulmonary artery pressures are not affected. The ejection fraction is
      not significantly affected. Left ventricular end-systolic and -diastolic volumes
      are reduced. There is regression of left ventricular hypertrophy after 6 months
      of treatment. Epinephrine, norepinephrine, and renin levels are all reduced, a
      finding consistent with central inhibition of sympathetic tone. After oral
      administration Tmax is about 1 h and bioavailability approaches 90%. Moxonidine
      is mostly excreted unchanged; biotransformation is unimportant. The T1/2 is 2.5
      h, prolonged by renal insufficiency. The antihypertensive effect lasts longer
      than would be expected from the half-life, suggesting possible retention in the
      CNS. Open studies with moxonidine have revealed decreases on the order of 20-30
      mm Hg systolic and 10-20 mm Hg diastolic blood pressure. Most patients are
      controlled by 0.2-0.4 mg daily. Moxonidine has been compared with representatives
      from each important class of antihypertensive drugs, with diuretics, clonidine,
      calcium antagonists, angiotensin-converting enzyme inhibitors, and both alpha-
      and beta- blocking drugs. Blood pressure control has been similar with moxonidine
      and these other agents. The overall incidence of side effects was similar,
      although moxonidine has a lower incidence of side effects than clonidine. Meta
      analysis of controlled studies with moxonidine indicates that moxonidine causes
      similar decreases in blood pressure in both male and female subjects, in those
      below 50 years, those 50-60 years, and those over 60 years old, regardless of
      body weight. As with some other drugs, higher systolic blood pressure are
      associated with larger falls of systolic blood pressure, and the same is true for
      diastolic blood pressure.

PMID- 8872299
TI  - Aspects of tolerability of centrally acting antihypertensive drugs.
AB  - Traditional centrally acting antihypertensives have been associated with a high
      incidence of adverse effects and are no longer recommended as first-line therapy.
      The newer imidazoline receptor agonists must overcome this reputation if they are
      to gain recognition as potential first-line agents for hypertension. Methyldopa,
      a centrally acting alpha(2)-agonist, is characterized by a number of serious
      adverse reactions that limit its use. Although unpredictable idiosyncratic or
      hypersensitivity reactions are uncommon, these include hepatitis, myocarditis,
      and hemolytic anaemia. Less serious problems such as abnormal liver function
      tests, positive Coombs test, drug-induced fever, and pancreatitis also occur.
      Central side effects include drowsiness, fatigue, lethargy, sedation, depression,
      psychotic reactions, nasal stuffiness, impotence, and exacerbation of
      Parkinsonism. In hypertensive men, methyldopa is less well tolerated than either
      captopril or propranolol, and up to 20% of patients discontinue therapy because
      of adverse effects. Clonidine acts primarily as an alpha(2)-agonist but also acts
      as an agonist at imidazoline receptors in the rostroventrolateral medulla. It is
      equipotent to most other antihypertensives but is considerably less well
      tolerated in comparative trials. The principal adverse effects of clonidine are
      drowsiness, sedation, lethargy and dry mouth. Reserpine acts primarily by
      depleting central catecholamine neurotransmitter stores. It was very extensively
      used in early hypertension trials, but its central side effects of sedation,
      nasal stuffiness, and severe depression are now considered so undesirable that
      the drug is seldom prescribed. The imidazoline (I1) agonists moxonidine and
      rilmenidine act selectively and have very little central alpha(2)-agonist
      activity. In comparative studies against placebo and other reference
      antihypertensives, the only adverse effect consistently associated with these
      drugs was dry mouth (approximate placebo-corrected incidence 10%). Sedation was
      not pronounced. Withdrawal syndromes are complex pathophysiologic processes and
      occur with a variety of antihypertensive drugs. Cessation of therapy with
      clonidine and, to a lesser extent, methyldopa may result in a severe withdrawal
      syndrome characterized by restlessness, sweating, anxiety, tremor, palpitations,
      and headache. There may be a rapid rise in blood pressure, often with a true
      "rebound" to higher than pretreatment levels. Plasma and urinary catecholamine
      levels are increased, and fatalities have been reported. It is important to
      stress that such a syndrome has not been recorded, in animal or human studies,
      with either moxonidine or rilmenidine.

PMID- 8872300
TI  - Future management of high blood pressure.
AB  - Both population (mass) strategies and targeted strategies for the management of
      high blood pressure are necessary. However, it has yet to be proven that reducing
      blood pressure by lifestyle changes in the population will confer the same
      cardiovascular benefit that results from lowering blood pressure by drugs. It is
      important to identify and correct those factors in hypertensive patients, such as
      obesity, smoking, elevated lipids, and diabetes, that confer high risk for an
      adverse cardiovascular event. It is now recognized that cardiovascular risk
      involves not only diet and lifestyle effects but that the structural and
      functional abnormalities resulting from high blood pressure are of great
      importance. There is a need to develop and validate new noninvasive methods for
      quantitating these structural and functional changes, together with assessment of
      endothelial dysfunction, hormonal profiling, and identification of susceptible
      genes so that high risk patients with hypertension can be selected for drug
      therapy. In the future, selection of an appropriate antihypertensive drug for an
      individual patient should also involve consideration of risk factors, structural
      changes, hormonal status, and genetic consideration. Central inhibition of
      peripheral sympathetic action by imidazoline receptor agonists, such as
      moxonidine, may lead to reversal of these structural and functional abnormalities
      without adverse effects on the central nervous system.

PMID- 8872301
TI  - Distinctions between hippocampus of mouse and rat: protein F1/GAP-43 gene
      expression, promoter activity, and spatial memory.
AB  - We began these experiments as an attempt to replicate in the mouse the induction
      by kainate (KA) of F1/GAP-43 mRNA we observed in adult rat hippocampal granule
      cells [Mol. Brain Res., 33 (1995) 22-28]. However, even though KA induced
      behavioral seizures in the mouse similar to those in the rat, neither induction
      of F1/GAP-43 mRNA nor subsequent mossy fiber sprouting observed in the rat was
      detected in three different mouse strains. It was also surprising that the
      distribution of constitutive levels of F1/GAP-43 mRNA in mouse and rat
      hippocampus was qualitatively different. Indeed, F1/GAP-43 expression in CA3
      pyramidal cells was significantly greater in rat than mouse, while F1/GAP-43
      expression in CA1 cells of rat and mouse was equivalent using densitometric
      analysis. Thus, F1/GAP-43 expression in rat is quantitatively higher in CA3 and
      CA1 pyramidal cells. In mouse, expression was equivalent in these two subfields.
      In a transgenic mouse bearing a rat F1/GAP-43 promoter-reporter (lacZ) construct
      (line 252), in-vivo promoter activity of F1/GAP-43 was studied in hippocampal
      cells. Transgene expression in hippocampal pyramidal subfields, high in CA3, low
      in CA1 pyramidal cells, paralleled the distribution of rat F1/GAP-43 mRNA levels,
      not mouse. Differences in the constitutive F1/GAP-43 expression pattern in
      hippocampus between rat and mouse may therefore be determined by different
      recognition elements present on the F1/GAP-43 promoter. KA injected into the line
      252 transgenic mouse did not activate the rat F1/GAP-43 promoter in mouse
      hippocampal granule cells. The absence of both F1/GAP-43 mRNA expression
      induction and promoter activation in mouse granule cells after KA is likely
      related to genera differences in transcriptional regulatory mechanisms, though
      post-transcriptional mechanisms cannot be excluded. Since the different
      hippocampal chemistry of F1/GAP-43 in rat and mouse likely extends to other
      molecular species, behaviors in rat and mouse that depend on hippocampal function
      might be different as well. We therefore evaluated spatial memory ability in a
      delayed matching-to-sample task. In contrast to rat, we were surprised to find no
      evidence of the ability to learn this task in three different mouse strains.
      Since interest in mouse genetics in relation to behavior and memory functions of
      hippocampus is growing, generalizations concerning hippocampal function from
      studies carried out on the mouse need to be made with caution considering the
      specific behavioral, pharmacological, and general molecular differences observed
      here. One can also be opportunistic and exploit the natural variations between
      these two genera to gain insight into the molecular mechanisms underlying
      information storage.

PMID- 8872302
TI  - Plasticity of tyrosine hydroxylase gene expression in the rat nucleus tractus
      solitarius after ventilatory acclimatization to hypoxia.
AB  - The aim of this study was to define the influence of long-term hypoxia on gene
      expression of tyrosine hydroxylase (TH) in the rat nucleus tractus solitarius
      (NTS). Animals were exposed to normobaric hypoxia (10% O2 in nitrogen) for 2
      weeks. At this time, the hypoxia-induced hyperventilation reached a plateau,
      indicating ventilatory acclimatization. In horizontal brainstem sections, hypoxia
      induced changes in TH protein and TH mRNA were assessed by immunocytochemistry
      and in-situ hybridization, respectively. Long-term hypoxia increased TH mRNA
      levels seen as both an increase in the number of grains per cell and an extension
      of the labeled area. The highest degree of labeling was found selectively located
      in caudal NTS. Hypoxia also enhanced TH immunoreactivity in the caudal NTS but
      this labeling extended more rostrally than that of TH mRNA. The data suggest that
      there is an hypoxia-induced plasticity of gene expression at the gene level in
      the NTS, which is associated with ventilatory acclimatization. The hypoxia model
      described in this study may serve as a framework for future regulatory studies.

PMID- 8872303
TI  - Use of a two-hybrid system to investigate molecular interactions of GAP-43.
AB  - We used the 'interaction trap' (two-hybrid system) to identify polypeptides that
      interact with the neuronal phosphoprotein, GAP-43, in an intracellular
      environment. GAP-43 (neuromodulin, B-50, F1), a protein kinase C (PKC) substrate
      important for the growth and plasticity of neuronal connections, has been
      implicated in vitro in several signal transduction pathways. In the yeast-based
      cloning system, the only strong interaction that was detected between GAP-43 and
      the calcium effector protein, calmodulin (CaM). PKC phosphorylates GAP-43 on
      serine 41. When we changed this serine to an aspartate residue to mimic
      constitutive phosphorylation, the interaction with CaM was blocked. Surprisingly,
      the N-terminal third of GAP-43 alone bound CaM more strongly than did intact GAP
      43, suggesting that the protein's C-terminus may play a role in modulating the
      interaction with CaM. These results, along with other recent findings, suggest a
      novel role for the interaction between GAP-43 and CaM.

PMID- 8872304
TI  - Murine central neurons express a novel member of the cdc10/SWI6 motif-containing
      protein superfamily.
AB  - V-1 protein is a novel member of the cdc10/SWI6 motif-containing protein
      superfamily several members of which have been demonstrated to play crucial roles
      in the regulation of intracellular signaling. In the present study we examined
      the distribution of V-1 mRNA in the murine central nervous system (CNS). Northern
      analysis revealed the expression of V-1 mRNA in various regions of the brain with
      the following rank order: hippocampus, cerebellum > cerebral cortex, olfactory
      bulb, medulla oblongata, pons > thalamus. In situ hybridization also showed that
      V-1 mRNA is widely distributed in various regions of the brain, with parallel
      expression levels to those revealed by Northern analysis. Immunohistochemical
      analysis revealed that the V-1 protein exists in various types of neurons, mainly
      in cell bodies but also in dendrites, axons and possibly in synaptic areas. These
      expression patterns of the V-1 gene in the murine CNS suggest that the V-1
      protein performs some common function in different classes of neurons. We found
      no significant difference in the expression level of V-1 mRNA in cerebellar
      granule cells between the control and mutant mice of Purkinje cell degeneration
      (pcd). In comparison with our previous data obtained in another mutant,
      staggerer, we discussed the effects of target deprivation on the expression of V
      1 mRNA in cerebellar granule cells.

PMID- 8872305
TI  - Postnatal phencyclidine treatment differentially regulates N-methyl-D-aspartate
      receptor subunit mRNA expression in developing rat cerebral cortex.
AB  - The present study was designed to determine the effects of chronic neonatal
      exposure to the NMDA receptor antagonist phencyclidine (PCP) on [3H]MK-801
      binding and on gene expression of NMDA receptor subunits in juvenile male rats.
      Rat pups were injected daily with PCP from day 5 to 15 and killed on day 21.
      [3H]MK-801 binding was measured by quantitative autoradiography. A sensitive
      RNase protection assay was employed to determine simultaneously the mRNA levels
      of NR1 subunit (comprising all different splice variants) and three NR2 subunits
      (NR2A-NR2C). The relative distribution profile of NMDA receptor subunits in the
      cerebral cortex was NR2B > NR1 > NR2A > NR2C and in the cerebellum NR2C = NR1 >
      NR2A = NR2B. Chronic PCP administration in postnatal rats produced significant
      reduction in both [3H]MK-801 binding and mRNA level of the NR2B subunit in the
      cerebral cortex. Expression of the other NMDA receptor subunits in the cerebral
      cortex did not change following the drug treatment. In the cerebellum, neither
      [3H]MK-801 binding nor any of the NMDA receptor subunit expression levels showed
      any alteration. Together, these data provide a molecular correlate for chronic
      postnatal PCP-induced down-regulation of [3H]MK-801 binding in rat cerebral
      cortex and suggest that the NR2B subunit plays an important role in developmental
      plasticity.

PMID- 8872306
TI  - Zygotic expression of the zebrafish Sox-19, an HMG box-containing gene, suggests
      an involvement in central nervous system development.
AB  - The zebrafish Sox-19 belongs to the Sry subfamily of HMG (Hight Mobility Group)
      box genes and is closely related to the Sox sub-group B, comprising the mouse Sox
      1, Sox-2 and Sox-3 genes, with respect to both HMG box homology (95.3%) and
      neural expression during embryogenesis. Analysis of Sox-19 expression during
      embryogenesis by whole-mount in-situ hybridization revealed interesting features.
      In early gastrula embryos, Sox-19 transcripts are detected within a circular area
      in the region of the presomptive central nervous system (CNS) and appears to be
      the earliest molecular marker of the CNS in vertebrates. In the developing brain,
      ZfSox-19 mRNA is distributed in the ventral region of the diencephalon, midbrain
      and hindbrain whereas the expression is excluded from the telencephalon. In spite
      of the ventral localisation of its mRNA, the expression of this ZfSox-19 gene is
      completely normal in cyclops embryos which implies that ZfSox-19 expression is
      independent of the presence of the floor plate.

PMID- 8872307
TI  - Two synaptotagmin genes, Syt1 and Syt4, are differentially regulated in adult
      brain and during postnatal development following kainic acid-induced seizures.
AB  - The synaptotagmins together with other vesicle proteins are thought to be
      essential for the docking and/or fusion of synaptic vesicles with the plasma
      membrane that occurs following depolarization and calcium influx in presynatic
      terminals. Syt4, the fourth identified member of the synaptotagmin family, is
      inducible in PC12 cells by depolarization and secretagogues, and in limbic
      regions of the adult rat brain by kainic acid-induced seizures. In the present
      study, we examined the time course of the seizure-induced changes in the
      expression of Syt4 and Syt1, both in adult animals and during the postnatal
      period. Syt4 was transiently induced in several structures of the adult rat brain
      following seizure activity with peak inductions between 4 and 8 h and overal
      return to control values by 30 h. No induction was observed following seizure
      activity in 7-day-old animals. The brain regions most sensitive to increased
      induction were, in decreasing order of sensitivity, hippocampal pyramidal cells
      dentate granule cells and piriform cortex pyramidal cells. The brain areas
      showing the greatest Syt4 stimulation in adults were also the areas in which Syt4
      was induced by seizures earlier in development. In contrast, Syt1 mRNA was
      depressed in adult brains following seizure activity, particularly in the dentate
      granule cells. Our results suggest that the differential regulation of different
      synaptotagmin genes following excessive neuronal activity might participate in
      rapid adaptation of subsequent transmitter release.

PMID- 8872308
TI  - Caprine homologue of rodent 5'-AMP-activated protein kinase subunit and yeast
      SNF4/CAT3 is down-regulated by thyroid hormone.
AB  - We isolated a cDNA, B12, that was down-regulated by thyroid hormone (TH) in the
      goat cerebellum, using a polymerase chain reaction (PCR)-based subtractive
      hybridization and differential screening procedure. Northern blot analysis of RNA
      from cerebellum of T4-treated and untreated hypothyroid goats confirmed that
      clone B12 was TH-regulated with an average reduction in expression of 21% after 4
      days of T4 supplementation. Other tissues from a T4-treated and an untreated
      hypothyroid goat also revealed down-regulation of B12, with the highest reduction
      in expression found in the thyroid gland (38%). Steady-state levels of the
      approximately 1.8 kb B12 mRNA were higher in brain than in peripheral tissues. In
      situ hybridization showed that B12 mRNA in the brain is mainly present in various
      layers of the cerebellum and the cerebral cortex, the hippocampus, and the
      olfactory tubercle and is predominantly expressed in neurons. Sequence analysis
      of the caprine B12 cDNA clone, and the murine homologue, revealed 61% similarity
      to SNF4/CAT3, a regulator involved in the transcriptional control of glucose
      repressible genes in yeast, and 99% identity to a rat 5'-AMP-activated protein
      kinase subunit, which is involved in the regulation of fatty acid, glycogen and
      isoprenoid metabolism. In view of these homologies, B12 might encode a regulator
      involved in distinct metabolic pathways and therefore, TH might also affect gene
      expression indirectly by down-regulation of regulators like B12.

PMID- 8872309
TI  - Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA
      fragmentation and ischemic cell damage following middle cerebral artery occlusion
      in rats.
AB  - Permanent occlusion of the middle cerebral artery in rats was used to assess the
      effects of focal ischemia on the expression of members of the bcl-2 family which
      have been implicated in the regulation of programmed cell death. Intraluminal
      occlusion of one middle cerebral artery for 6 h resulted in histologically
      detectable brain damage within the ipsilateral caudate putamen, basolateral
      cortex and parts of the thalamus. In the infarcted basolateral cortex and
      thalamus fragmentation of DNA was detected in many nuclei using in-situ end
      labeling of DNA breaks by terminal transferase, whereas only scattered labeled
      nuclei were visible in the infarcted caudate putamen. Immunohistochemical
      analysis revealed activation of c-Fos in the infarcted cortex and thalamus and in
      the non-infarcted cingulate cortex as has been shown by others. A decrease in
      immunoreactivity for Bcl-2, and Bcl-X and an increase in immunostaining for Bax
      was observed exclusively in neurons within the ischemic cortex and thalamus.
      Within the infarcted caudate putamen, however, protein levels of all bcl-2 family
      members declined and c-Fos remained absent. By reverse transcription and
      polymerase chain reaction it was demonstrated that levels of bcl-2 mRNA markedly
      decreased in the ipsilateral hemisphere, whereas the amount of bax mRNA was
      elevated. These findings suggest that a shift in the ratio of cell death
      repressor Bcl-2 to cell death effector Bax and a concomitant activation of c-Fos
      may contribute to neuronal apoptosis in the infarcted thalamus and cortex.

PMID- 8872310
TI  - Chronic morphine administration enhances the expression of Kv1.5 and Kv1.6
      voltage-gated K+ channels in rat spinal cord.
AB  - Prolonged opiate administration leads to the development of tolerance and
      dependence. These phenomena are accompanied by selective regulation of distant
      cellular proteins and mRNAs, including ionic channels. Acute opiate
      administration differentially affects voltage-dependent K+ currents. Whereas,
      opiate activation of K+ channels is well established opioid-induced inhibition of
      K+ conductance has also been studied. In this study, we focused on the effect of
      chronic morphine exposure on voltage-dependent Shaker-related Kv1.5 and Kv1.6 K+
      channel gene expression and on Kv1.5 protein levels in the rat spinal cord.
      Several experimental approaches including in-situ hybridization, RNAse
      protection, reverse transcriptase-polymerase chain reaction (RT-PCR), Western
      blotting and immunohistochemistry were employed. We found that motor neurons are
      highly enriched in Kv1.5 and Kv1.6 mRNA and in Kv1.5 channel protein. Moreover,
      we found significant increases in the amount of mRNA encoding for these two K+
      channels and in Kv1.5 channel protein in the spinal cord of morphine-treated
      rats, compared with controls. For example, quantitative in-situ hybridization,
      revealed a 2.1 +/- 0.15- and 2.3 +/- 0.5-fold increase in Kv1.5 and Kv1.6 channel
      mRNA levels, respectively. Similar results were obtained by semiquantitative RT
      PCR analyses. Kv1.5 protein level was increased by 1.9-fold in the spinal cord or
      morphine-treated rats. Our results suggest that Kv1.5 and Kv1.6 Shaker K+
      channels play an important role in regulating motor activity that increases in
      mRNA and protein levels of the spinal cord K+ channels after chronic morphine
      exposure could be viewed as a cellular adaptation which compensates for a
      persistent opioid-induced inhibition of K+ channel activity. These alterations
      may account, in part, for the cellular events leading to opiate tolerance and
      dependence.

PMID- 8872311
TI  - Time-dependent changes in NMDA receptor expression in neurones cultured from rat
      brain.
AB  - Several studies have shown marked changes in the regional expression pattern of N
      methyl-D-aspartate (NMDA) receptor subunit composition in vivo in the developing
      brain. Similar developmental changes may also occur in vitro. Thus, displacement
      of [3H]MK-801 binding by the subunit-selective NMDA antagonist, ifenprodil, in
      membrane homogenates prepared from cultured neurones, has been shown to comprise
      two components, the relative proportion of which changed with time in culture
      [11]. In the present experiments we have used electrophysiological methods to
      determine the influence of time in culture on NMDA receptor subtype expression
      pattern in individual neurones. Shortly after plating (13 days in vitro (DIV)),
      approximately 70% of total NMDA-induced inward current in voltage-clamped rat
      cortical neurones is antagonised by ifenprodil with relatively high affinity
      (approximately 1 microM). By 65 DIV, however, the high-affinity component
      contributed to only approximately 20% of the overall antagonism. Cerebellar
      granule cells also appear to undergo a similar change in their NMDA receptor
      expression with the exception that, in general, they appear initially to show
      considerably less of the ifenprodil high-affinity component and this disappears
      completely by 15 DIV. These experiments suggest that individual cortical and
      granule cells express at least two different NMDA receptor subtypes and that
      their relative proportion changes with time in culture.

PMID- 8872312
TI  - Co-expression of steroid hormone receptors in opioid peptide-containing neurons
      correlates with patterns of gene expression during the estrous cycle.
AB  - The anteroventral periventricular nucleus (AVPV) of the preoptic region
      represents an essential component of neural pathways regulating gonadotropin
      secretion, and contains sexually dimorphic populations of neurons that express
      dynorphin or enkephalin. In the present study we used in situ hybridization to
      measure prodynorphin (PDYN) and proenkephalin (PENK) mRNA in the AVPV of intact
      animals killed on each day of the cycle. Levels of PDYN mRNA were lowest in
      animals killed on the afternoon of proestrus and then increased by over 60% by
      the morning of the following day. Expression of PENK mRNA was generally stable
      during the cycle, but a small yet significant reduction was detected on proestrus
      relative to levels of PENK mRNA in animals killed on the day of diestrus. In
      addition, we used double in situ hybridization to demonstrate that the majority
      of PDYN mRNA-containing neurons express both estrogen (50%) and progesterone
      receptor (85%) mRNAs. Only one quarter of the PENK-containing neurons also co
      express estrogen receptor mRNA, and fewer than 10% of the PENK mRNA neurons
      express PR mRNA. Thus, the differential expression of PDYN and PENK during the
      cycle generally correlates with distinct differences in the degree of
      colocalization of ER and PR mRNA in PDYN and PENK mRNA-containing neurons in the
      AVPV.

PMID- 8872313
TI  - Expression of the calcium-binding protein, parvalbumin, in cultured cortical
      neurons using a HSV-1 vector system enhances NMDA neurotoxicity.
AB  - Calcium-binding proteins (CaBPs) are a family of proteins having a unique
      distribution in the brain and are thought to be important in buffering
      intracellular calcium. Glutamate neurotoxicity is a process by which the over
      activation of glutamate receptors can cause the influx of excessive extracellular
      calcium and neuronal cell death. It has been proposed that neurons containing
      CaBP may be more resistant to glutamate neurotoxicity due to their increased
      ability to buffer calcium. Using a herpes simplex virus-1 (HSV-1) vector system
      we packaged the CaBP gene, parvalbumin, or the marker gene, beta-galactosidase
      (beta-gal), correctly in viron particles, which were found upon infection to
      express mRNA specific to these vectors. PC12 and neocortical cultures showed
      strong immunohistochemical staining for either beta-gal or parv. The cortical
      cultures stained positively for endogenous glutamate decarboxylase, a marker for
      GABAergic neurons, but not for endogenous parvalbumin, indicating that
      parvalbumin was being expressed ectopically from the HSV-1 vector. Interestingly,
      the expression of parvalbumin increased cortical culture's susceptibility to N
      methyl-D-aspartate-induced neurotoxicity. This increase in neurotoxicity was not
      due to the wild-type virus or the helper virus which accompanies the packaging of
      these vectors. We speculate that the ectopic expression of parvalbumin in
      cortical cultures may be increasing glutamate release which in turn increases
      cell death.

PMID- 8872314
TI  - Biochemical and functional characterization of the synaptic vesicle-associated
      form of CA2+/calmodulin-dependent protein kinase II.
AB  - Ca+/calmodulin-dependent protein kinase II (CaMPKII) is a brain-enriched protein
      kinase that plays important roles in synaptic transmission and plasticity. In
      nerve terminals, a form of CaMPKII is associated with synaptic vesicles and binds
      the COOH-terminal region of synapsin I (SYNI). The biochemical properties of the
      vesicle-associated form of CAMPKII have been investigated and compared with those
      of the soluble forebrain enzyme. Both the alpha- and beta-subunits of CaMPKII
      copurifying with synaptic vesicles were tightly associated with the vesicle
      membrane. The vesicle-associated form of CaMPKII was indistinguishable from the
      soluble form with respect to sites of autophosphorylation, kinetics of both
      autophosphorylation and SYNI phosphorylation, and induction of autonomous
      activity upon autophosphorylation. Although both subunits of the soluble CaMPKII
      interacted with a photoactivatable SYNI derivative, only the alpha-subunit of the
      synaptic vesicle-associated CaMPKII bound to the COOH-terminal region of SYNI.
      The latter interaction was strongly dependent on the phosphorylation state of
      SYNI and on divalent cations, but appeared to be independent of
      autophosphorylation. These results demonstrate that, although the vesicle
      associated form of CaMPKII is catalytically indistinguishable from the soluble
      form, it exhibits distinct characteristics concerning its association with the
      vesicle membrane and with SYNI.

PMID- 8872315
TI  - CRH-R1 mRNA expression in two strains of inbred mice and its regulation after
      repeated restraint stress.
AB  - Using in-situ hybridization histochemistry we investigated the distribution of
      CRH receptor 1 (CRH-R1) mRNA in the cortex of C57BL/6 (C57) and DBA/2 (DBA)
      strains and its regulation after repeated restraint stress. We show that DBA mice
      have a higher concentration of CRH-R1 mRNA than C57 mice. Repeated restraint
      stress produced an increase in CRH-R1 mRNA expression of C57 mice, whereas it was
      uneffective in DBA mice.

PMID- 8872316
TI  - The role of torus longitudinalis in equilibrium orientation measured with the
      dorsal light reflex.
AB  - The torus longitudinalis (TL) is a paired elongated structure reciprocally
      connected with the optic tectum in actinopterygian fishes. Electrophysiological
      recordings have revealed a sustained neural discharge in TL inversely related to
      luminance [Northmore, 1984]. This photometric response may play a role in the
      comparison of light levels between the two eyes, which must occur for the dorsal
      light reflex (DLR) to orient the body in the environment. Based on the luminance
      response of TL, it was hypothesized that TL ablation would result in a reduced
      DLR. Individual goldfish (Carassius auratus) were observed with variable and
      constant light sources on opposite sides of a test tank. The DLR was measured
      with respect to angle (degree) and duration (seconds) of body tilt about the
      longitudinal axis. After baseline readings were obtained, the intertectal
      commissure was cut and TL was removed bilaterally. Surgical control fish had only
      the intertectal commissure cut. Following surgery, TL ablatees showed a
      significantly reduced DLR compared to controls. The results are consistent with
      the suggestion by Northmore [1984] that TL may be involved in the processing of
      luminance information.

PMID- 8872317
TI  - Unusual pattern of retinogeniculate projections in the controversial primate
      Tarsius.
AB  - Studies of simian and prosimian primates have demonstrated a remarkable
      interspecific constancy in the pattern of innervation of the magnocellular and
      parvocellular layers of the dorsal lateral geniculate nucleus (dLGN) by retinal
      afferents. The characteristic organization of this nucleus in primates, as well
      as its apparent phylogenetic stability, have led to the proposal that the
      distinct laminar arrangement of the dLGN is one of the diagnostic characters that
      define the Order Primates. Here, we describe the distribution of retinal
      afferents to the dLGN of Tarsius, the single contemporary member of an ancient
      lineage of primates. In this genus, the more superficial layer of the dLGN
      receives projections from the ipsilateral eye, a unique situation among the
      members of the Order Primates. This observation adds support to the proposal that
      Tarsius does not share a more recent common ancestry with simians as compared
      with lemuriform and lorisiform primates.

PMID- 8872318
TI  - The closed-loop nature of the tymbal response in the dogbane tiger moth, Cycnia
      tenera (Lepidoptera, Arctiidae).
AB  - The dogbane tiger moth, Cycnia tenera, emits ultrasonic sounds by rhythmically
      buckling a pair of tymbals when stimulated by pulsed sounds resembling bat
      echolocation. We monitored the central pattern generator governing this response
      by recording the motor output of the tymbal branch of the metathoracic leg nerve.
      The rhythm of the tymbal motor pattern can be altered midway (500 m/sec from its
      initiation) by changing the period and, to a lesser degree, the intensity of the
      stimulus. The tymbal response of C. tenera is therefore closed-looped to stimulus
      pulse period and intensity. Our results suggest that C. tenera relies less on the
      changes in an attacking bat's echolocation intensity when responding with this
      behaviour because this acoustic parameter may be a more unreliable indicator of
      the proximity of the bat than its echolocation call period.

PMID- 8872319
TI  - Hierarchical sensory guidance of mauthner-mediated escape responses in goldfish
      (Carassius auratus) and cichlids (Haplochromis burtoni).
AB  - Acoustically-evoked escape behaviors were compared between goldfish (Carassius
      auratus), a hearing specialist, and the cichlid Haplochromis burtoni, a hearing
      nonspecialist. Fish were startled with compressive and rarefying, stimuli
      presented alone or together, and with compressive pulses preceded by a visual cue
      or after exposure to cobalt, an inhibitor of lateral line-innervated neuromast
      hair cells. These acoustic startle stimuli can evoke Mauthner neuron firing and
      are similar to but weaker than those produced by a largemouth bass (Micropterus
      salmoides) feeding on guppies. When sound stimuli were presented alone, both
      species avoided the direction of either the compressive or rarefying stimulus. If
      a light preceded and was contralateral to the compressive sound pulse, goldfish
      continued to avoid the sound source; cichlids avoided the visual cue and turned
      toward the sound. Goldfish performance improved significantly when the visual cue
      was in the same direction as the sound source. Goldfish performance also improved
      significantly after exposure to 0.1 mmol l-1 cobalt solution for 24 hours before
      testing, but cichlids would not startle after cobalt acclimation. A compressive
      pulse presented to one side of a fish simultaneously with a rarefying pulse on
      the other side causes the entire fish to accelerate with the water current. This
      strongly and directly accelerates the ear but tends to reduce both the pressure
      changes transduced by the swimbladder and activation of the mechanosensory
      lateral line. In this test, goldfish reliably avoided the compressive pulse.
      Cichlids, however, randomly avoided either speaker polarity but significantly
      avoided the speaker which had a faster onset. With more closely matched speakers,
      cichlids also preferentially avoided the compressive stimulus. Thus, the
      primitive sensory condition for auditory activation and guidance of Mauthner
      neuron-initiated escape responses may have evolved to detect the initially
      compressive sounds associated with ram-type predators.

PMID- 8872320
TI  - Ontogeny of suckling mechanisms in opossums (Didelphis virginiana).
AB  - Although adult mammals have several different mechanisms for drinking liquids,
      relatively little is known about the variation in mechanisms used by infants for
      suckling and how the mechanics of suckling change as a function of ontogeny. We
      examined suckling in infant opossums, animals that as adults use a lapping
      mechanism to drink. The youngest infants (45 days old) used a suction, pumping
      mechanism, based on dorsal/ventral tongue movements, similar to what has been
      documented in infant primates and pigs. However, slightly older infants (66 days
      old), when removed from their mother, used a lapping or licking mechanism that is
      closer to the anterior/posterior tongue movements that adult opossums use during
      drinking. Littermates remaining with the mother continued to use the pumping
      mechanism observed in the youngest animals. These older animals lacked teeth and
      were not physiologically mature enough to live independently of their mothers. We
      conclude that the neural controls for two distinct feeding mechanisms exist
      simultaneously in infant opossums and that the change from a suckling, infantile
      motor pattern to an adult lapping one is not strictly a temporal change.

PMID- 8872321
TI  - The role of the vomeronasal organ in rattlesnake (Crotalus viridis oreganus)
      predatory behavior.
AB  - During predatory behavior, rattlesnakes depend primarily upon thermal and visual
      cues to initially aim a strike. However, it has been hypothesized that prey
      related odors sensed by the vomeronasal system act as releasing stimuli of the
      strike and that such vomodors are primary stimuli during poststrike trailing and
      swallowing of the envenomated rodent. To test this, northern Pacific rattlesnakes
      were rendered avomic by bilateral lesions of the vomeronasal nerves, and their
      vomic and avomic predatory behaviors were compared. Avomic rattlesnakes exhibited
      fewer strikes and complete elimination of trailing and swallowing behavior. These
      results support the hypothesis that vomodors sensed via the vomeronasal organ are
      capable of acting as releasing stimuli of selected rattlesnake predatory
      behaviors. Sensory input via the vomeronasal organ is important during
      prestrike/strike behavior, and it is a major route of sensory input during
      poststrike trailing and ingestion of envenomated prey.

PMID- 8872322
TI  - An enzyme-linked immunosorbent assay for the determination of src-family tyrosine
      kinase activity in breast cancer.
AB  - An enzyme-linked immunosorbent assay is described for the determination of
      protein tyrosine kinase activity originating from the presence of src-like
      tyrosine kinases in biological samples. In this assay a peptide derived from
      p34cdc2, cdc2(6-20)NH2, is coupled to the wells of a maleic anhydride-activated
      microtiter plate. This particular peptide has been described as an efficient and
      specific substrate for protein tyrosine kinases belonging to the src family
      kinases (Cheng et al., J.Biol.Chem. 267 (1992) 9248-9256). After incubation of
      the coated substrate with sample and ATP, the amount of phosphorylated tyrosyl
      residues is determined with phosphotyrosine specific antibodies and a secondary
      peroxidase-labeled antibody. The assay appears to be very sensitive and is linear
      with sample protein concentration and phosphorylation time. Intra-assay variation
      is < 5%, whereas day-to-day variation is < 10%. The results of the assay have
      been compared with an ELISA in which the broad-specificity tyrosine kinase
      substrate poly(GluNa,Tyr)4:1 was coated. The results of both assays in 27
      cytosolic breast cancer samples correlated very well (r = 0.94), in accordance
      with the predominant expression of src kinase activity in breast cancers
      (Ottenhoff-Kalff et al., Cancer Res. 52 (1992), 4773-4778). The present assay
      provides an easy, reproducible, and quick alternative for the usual radioactive
      methods used for the determination of src-kinase activities including
      immunecomplex kinase assay and TCA-precipitation assays. It allows the
      determination of src-like activities in human tumors for routine diagnostic
      purposes.

PMID- 8872323
TI  - Cell cycle expression of estrogen receptors determined by image analysis on human
      breast cancer cells in vitro and in vivo.
AB  - We have investigated, by image analysis, the cell cycle expression of estrogen
      receptors (ER) on MCF-7 cell line and on MCF-7 xenografts. The results
      demonstrate, in vitro as well as in vivo, an increase of ER concentration during
      the G0/G1-phase, followed by a decrease during the S-phase until the late S-phase
      where a rapid increase was noted. These results confirm that estrogens are
      involved in the DNA synthesis since ER is expressed in vivo at a maximal level in
      the late G1. In presence of saturating concentrations of 17 beta-estradiol, the
      mean ER concentration in G0/G1 phase is significantly decreased compared with the
      control cells cultured in estrogen-deprived medium. This indicates that 17 beta
      estradiol down-regulates ER preferentially in the G0/G1 phase. These data suggest
      that ER in S and G2/M phases is unable to interact with its ligand. Consequently,
      estrogens may have no effects on the entry of cells in mitosis. Finally, after
      long-term tamoxifen treatment of MCF-7 xenografts, a tamoxifen-resistant tumor
      was developed which was characterized by a change in the profile of ER
      concentration during the G0/G1 phase. In conclusion, it is possible that the
      differences in cell cycle distribution of ER could be correlated with different
      phenotypes of breast cancer and also with different clinical phases of tumoral
      evolution. However, it remains to be known what is the clinical significance of
      the ER cell cycle expression in relation to tumor aggressiveness and survival.

PMID- 8872324
TI  - Advanced breast cancer: a randomized study of doxorubicin or mitoxantrone in
      combination with cyclophosphamide and vincristine.
AB  - BACKGROUND: Drug selection for the treatment of advanced breast cancer is based
      on both efficacy and toxicity. Combination chemotherapy produces higher response
      rates than single agents, of which doxorubicin is the most active. This study
      compares efficacy and toxicity of the drugs doxorubicin and mitoxantrone when
      used as part of a 3 drug combination. Doxorubicin is the most active agent, but
      also one of the most toxic, and in this study was compared, in a 3-drug
      combination, with mitoxantrone with the aim of achieving comparable efficancy
      with reduced toxicity. PATIENTS AND METHODS: 110 patients with advanced breast
      cancer previously untreated by chemotherapy were randomized to receive
      cyclophosphamide and vincristine, together with either doxorubicin 50 mg/m2 i.v.
      (VAC) or mitoxantrone 10 mg/m2 (VNC) for up to 6 cycles. RESULTS: Of 53 eligible
      patients randomized to VAC, the overall response rate was 55% (CR rate 17%),
      while of 55 patients randomized to VNC the overall response rate was 42% (CR rate
      7%). The difference is not statistically significant (p = 0.07), but there was a
      trend towards a higher response rate to VAC in patients aged less than 60, those
      with nodal and soft tissue disease, and those with 2 or more sites of disease.
      The principal difference in toxicity was reduced alopecia in favour of VNC.
      However there was also an increased number of deaths within the first cycle in
      patients randomized to VAC. There were no differences in survival, relapse free
      interval, or freedom from progression between the two arms. CONCLUSIONS: Both VAC
      and VNC are effective regimens in advanced breast cancer. While the confidence
      limits in this study mean the response rate advantages of VAC could have arisen
      by chance, younger patients with adverse prognostic factors may warrant
      consideration of the VAC regimen.

PMID- 8872325
TI  - Demonstration of silver-stained nucleolar organizer region associated proteins
      (AgNORs) after wet autoclave pretreatment in breast carcinoma: correlation to
      tumor stage and long-term survival.
AB  - Argyrophilic nucleolar organizer region associated proteins (AgNORs) are known to
      reflect cellular and nucleolar activity. Due to a novel staining procedure, which
      substantially improves visualisation of AgNORs on formalin-fixed and paraffin
      embedded material, AgNORs can be reliably demonstrated as true substructures of
      the nucleoli. The aim of the present study was to apply a standardized
      morphometric AgNOR quantification on a large series of breast carcinomas with
      regard to its prognostic relevance. AgNOR quantity was evaluated on archival
      tumor tissues of 115 adenocarcinomas of the breast treated with the wet autoclave
      method prior to standardized silver-staining and morphometric analysis. AgNOR
      parameters were correlated to prognostic features (steroid hormonal receptor
      status, tumor type, tumor size, histological grading, pTNM, and UICC stage)
      carrying out both univariate and multivariate survival analyses. AgNOR number and
      area were proven to be statistically significantly related (Pearson correlation
      coefficient: 0.67, Bonferroni adjusted P = 0.0001). Almost all AgNOR parameters,
      in particular CV (coefficient of variation) of corrected area (delta-area) and CV
      of number, were statistically significantly correlated to estrogen and
      progesterone receptor status as well as histological grading of tumors. Increased
      AgNOR parameters were statistically significantly associated with early tumor
      relapse and cancer related death. Univariate and multivariate analysis by means
      of Cox regression revealed independent prognostic significance for CV of delta
      area and number of AgNORs. Various AgNOR parameters (CV of number, CV of delta
      area, CV of area, mean delta-area, and mean area of AgNORs per nucleus)
      determined on wet autoclave pre-treated formalin-fixed and paraffin-embedded
      breast cancer tissues are statistically highly significantly associated with the
      prognostic outcome, independently predicting tumor-free and overall survival.

PMID- 8872326
TI  - Technical approach for the study of the genetic evolution of breast cancer from
      paraffin-embedded tissue sections.
AB  - We have optimized a technique that allows the study of numerous chromosomal loci
      (n = 20-50) from single paraffin-embedded tissue sections by microsatellite
      length polymorphism analysis. DNA samples from normal and breast cancerous tissue
      can be obtained from the same section by means of microdissection. This technique
      was further improved by subjecting DNA to several cycles of amplification with a
      degenerate (universal) primer and then with specific microsatellite primers. This
      amplified DNA was also used to screen for mutations in the p53 gene by means of
      PCR-SSCP. In addition adjacent tissue sections were used to assess specific
      chromosome copy number by interphase cytogenetic analyses (chromosome in situ
      hybridization) and to analyze expression of specific genes such as p53 and ERBB2.
      As an example of the use of our approach we performed a detailed chromosome 17
      allelotypic analysis in 22 breast tumors (5 ductal carcinomas in situ, 13
      invasive ductal carcinomas, and 4 invasive lobular carcinomas). We detected
      mutations in the p53 gene by PCR-SSCP in 36% of the samples. Samples with
      significant levels of p53 protein accumulation detected by immunohistochemistry
      were also positive for mobility shifts in the SSCP analysis. We observed that
      chromosome 17 allelic losses and imbalance occurred at as early a stage as ductal
      carcinoma in situ (DCIS). Although in some cases we observed allelic losses or
      imbalance affecting the 17p13 region, close to the p53 locus, several of the
      tumors showed dissociation between such loss or imbalance and p53 mutation.
      Lobular carcinomas were predominantly disomic for chromosome 17 in contrast with
      ductal tumors, which often showed polysomy for chromosome 17. This comprehensive
      approach correlating the tumor subtype, its allelotype, with specific chromosome
      copy number and specific gene mutations and expression in preinvasive or early
      invasive breast cancer lesions will potentially provide information of relevance
      for a better understanding of the multistep mechanisms of breast carcinogenesis.

PMID- 8872327
TI  - Postsynthetic regulation of insulin-like growth factor-binding protein-3 by MCF-7
      human breast cancer cells in culture.
AB  - Breast cancer cells are exposed to insulin-like growth factors (IGFs) which
      stimulate their proliferation, and to IFG-binding proteins (IGFBPs) which
      sequester and modulate IGF action. The primary circulatory IGFBP is IGFBP-3. In
      the present study, cultured MCF-7 breast cancer regulated clearance of IGFBP-3
      via both cell association and proteolysis. Exogenously added IGFBP-3 was
      significantly cleared from the medium over time yielding the formation of smaller
      sized immunodetected fragments. Clearance was inhibited by IGF-I and -II. In
      contrast, clearance was not affected by growth factors and an IGF-analog having
      mitogenic activity but not binding to IGFBPs. In fact, activity of the IGFs and
      analogs paralleled their degree of binding to the IGFBP, suggesting that the IGF
      binding altered IGFBP-3 making it less susceptible to clearance. Qualitatively
      similar results were obtained when these experiments were conducted using cell
      free conditioned medium, thus suggesting the presence of secreted protease(s).
      However, level of proteolytic activity was much less than that found in the
      presence of cells. Clearance of rhIGFBP-3 also involved binding to the cell.
      Disappearance of rhIGFBP-3 was shown to be attenuated by heparin, which blocks
      cell surface binding sites. In contrast, compounds which block internalization
      did not inhibit IGFBP-3 clearance.

PMID- 8872328
TI  - Absence of human papillomavirus DNA in breast cancer as revealed by polymerase
      chain reaction.
AB  - Oncogenic human papillomavirus (HPV) types 16 and 18 commonly associated with
      cervical cancer are found in many epithelial malignancies at extra-genital sites
      including breast. The transforming gene products of HPV have also been shown to
      immortalize breast epithelial cells in vitro. But the findings of HPV DNA in
      breast carcinoma are found to be contradictory. In the present study fine needle
      aspirate cell (FNAC) samples from 26 breast cancer patients and four breast
      tumour biopsies were analysed for the presence of HPV 16 and 18 DNA sequences by
      both polymerase chain reaction (PCR) and Southern blot hybridization. Of 26 fine
      needle aspirate cell samples and four breast cancer biopsies, not a single sample
      was found to be positive by either PCR or Southern blot hybridization. The
      observation of complete absence of HPV DNA sequences in breast cancer refute the
      possibility of any role for oncogenic genital HPV types 16 and 18 in the
      pathogenesis of breast cancer.

PMID- 8872329
TI  - FISH detection of HER-2/neu oncogene amplification in early onset breast cancer.
AB  - HER-2/neu (c-erbB-2) gene amplification based on Southern blotting or
      immunohistochemistry has been shown to be predictive of poor outcome in breast
      cancer occurring in women over 40, but there is little data on the role of HER
      2/neu in young women with breast cancer, many of whom may have inherited BRCA1 or
      other predisposing genes. The present study used fluorescent in situ
      hybridization (FISH) on archival specimens of breast cancer from 37 women under
      the age of 40 to evaluate the role of HER-2/neu amplification in this cohort, and
      to also evaluate the efficacy of FISH for quantifying amplification. The
      frequency of primary tumors with a greater than fourfold increase in gene copy
      number was found to be 38%, which is similar to the frequency of amplification
      reported in Southern blot studies in older women. However, the greater
      sensitivity of FISH enabled detection of low level amplification (more than 2 but
      less than 8 gene copies), which was found in an additional 30% of the tumors.
      Patients with low level amplification demonstrated a 54% recurrence rate,
      compared to 86% in those with high amplification and 17% in those with no
      amplification. HER-2/neu amplification appeared to be more prognostic of
      recurrence than nodal status, with 45% of node negative tumors recurring compared
      to 62% of those which were node positive, nor was tumor size predictive of
      recurrence in this cohort since tumors of 2 cm or less recurred in 44% of cases
      compared to 57% of those larger than 2 cm. Thus, this study demonstrates that
      FISH is a reproducible and sensitive technique for detecting HER-2/neu
      amplification, and that amplification of the oncogene is the strongest
      independent indicator of recurrence of breast cancer in young women.

PMID- 8872330
TI  - Prognostic significance of c-erb-B2 amplification in fine-needle biopsies of
      breast cancer patients not operated at diagnosis.
AB  - Prognostication of breast cancer patients, not operated at diagnosis, poses a
      clinically difficult problem. To use gene amplification we examined cytological
      samples and determined c-erb-B2 gene copy number with semi-quantitative PCR.
      Control experiments showed the same gene-copy number in aliquots that were either
      air-dried (and MGG-stained), fixed in methanol (and air-dried), or snap-frozen in
      liquid nitrogen. Therefore we examined the prognostic value of c-erb-B2
      amplification in 95 breast cancer patients that had not been operated at
      diagnosis (up to 12 years previously). Tumor cells were obtained from routine
      archival cytological smears. 15 patients (16%) had developed amplification.
      Univariate and multivariate analysis showed that c-erb-B2 amplification is a
      significant prognostic factor (p < 0.0001). Hence routine cytological MGG smears
      can be used for prognostic determination.

PMID- 8872331
TI  - Cathepsins D, B, and L in transformed human breast epithelial cells.
AB  - To investigate the regulation of lysosomal enzymes during carcinogenesis, we
      measured cathepsins (Cats) D, B, and L in MCF-10F, which is a human breast
      epithelial cell line, and cells evolved after treatment with carcinogen and
      transfected with c-Ha-ras oncogene. The clones used in this study, MCF-10FTras,
      D3, D3-1, and D3-1Tras, expressed no estrogen receptors and gradually increased
      invasive potential, while oncogene-transfected lines were also tumorigenic in
      SCID mice [16, 19]. Cats D, B, and L were determined in the cells and in cell
      media using enzyme-linked immunosorbent assay (ELISA), specific enzyme activity
      measurements, and immunocytochemistry. The major intra- and extracellular
      lysosomal proteinase in these cells was Cat D (30-180 pm/mg), followed by Cat B
      (2-10 pm/mg) and Cat L (1-5 pm/mg). An inverse relationship between intracellular
      Cat D levels and invasive potential of carcinogen-treated and c-Ha-ras oncogene
      transfected cell lines was observed. No significant changes in extracellular
      concentration of Cat D precursor in this series of cell lines was observed.
      Intracellular levels of Cats B and L were unchanged or slightly lower in
      carcinogen-treated D3 and D3-1 cells, as well as in MCF-10FTras. On the other
      hand, in D3-1Tras cell line, evolving from c-Ha-ras transfected D3-1 line, 3.5
      fold and 4.4 fold increases in Cat B and Cat L, respectively, but a 2 fold
      decrease in Cat D, were observed compared to the parental cell line.
      Immunocytochemical staining showed a granular, polarized perinuclear and
      cytoplasmic staining of cathepsins in all cell lines. Cysteine proteinases
      stained more frequently and more intensely in D3-1Tras compared to other lines,
      confirming the immunochemical assays. We hypothesize that several molecular
      events, caused by a carcinogen and an oncogene such as c-Ha-ras, are needed to
      increase Cat B and Cat L, but not Cat D, expression. Therefore, the cysteine and
      aspartic lysosomal proteinases are differentially expressed in the breast cell
      lines with more invasive phenotype.

PMID- 8872332
TI  - Tamoxifen and interferon-beta for the treatment of metastatic breast cancer.
AB  - It has been demonstrated, both in breast cancer cell lines and in metastatic
      breast cancer patients with cutaneous lesions that could be biopsied, that
      treatment with interferon beta (IFN-B) can increase expression of both estrogen
      (ER) and progesterone receptors (PgR). To evaluate the efficacy and toxicity of
      the combination of IFN and tamoxifen, 33 metastatic breast cancer patients were
      treated with the following regimen: IFN-B, 6.0 million units intramuscularly IU 3
      times a week for two consecutive weeks followed by IFN-B 6.0 million IU im 3
      times a week with concomitant tamoxifen 20 mg orally daily. Patients were pre and
      postmenopausal with median age of 60 years, median ECOG PS of 0, either ER
      positive or unknown, and had not received prior hormone therapy for metastatic
      disease. Overall objective response was observed in 9 (27%) patients. Complete
      response was observed in 2 cases and partial response in 7 patients. Median
      duration of response was 7 months (range 2-10). A higher response rate was
      observed in patients with predominantly soft tissue disease (38%) compared to
      patients with either dominant bone (18%) or visceral lesions (17%). Toxicity was
      mild and reversible: low grade fever in 30% of patients and flu-like symptoms in
      9% of cases. It appears that IFN-B does not improve the efficacy of tamoxifen in
      an unselected population of metastatic breast cancer.

PMID- 8872333
TI  - Endoglin/CD 105 may not be an optimal tumor endothelial treatment target.

PMID- 8872334
TI  - The Health of the Nation.

PMID- 8872336
TI  - Evolving health care.

PMID- 8872335
TI  - Priorities in medical research.

PMID- 8872337
TI  - Training clinical academics for the future.

PMID- 8872338
TI  - Genes in diagnosis and therapy.
AB  - With the recent exponential increase in our knowledge of human genes it is
      opportune to assess the impact this information will make on current clinical
      practice. In this review particular attention is paid to the advances being made
      in diagnostic techniques and to the possibilities for improved forms of
      treatment, particularly the use of recombinant gene products and somatic gene
      therapy.

PMID- 8872339
TI  - Addiction.
AB  - Addiction to tobacco, alcohol and drugs is a major problem. Dependence and
      problem drug use are now defined syndromes and their psychological, genetic and
      brain mechanisms are being elucidated. Social policy can influence the
      consumption of drugs and treatment strategies are becoming more effective.

PMID- 8872340
TI  - Fetal and perinatal medicine.
AB  - Fetal medicine, like this journal, is about 30 years old. In the 1960s access to
      the fetus was only possible around the time of birth, leading to the concept of
      'perinatal medicine'. However, as ultrasonography, invasive procedures and
      genetics provided the necessary tools, it became clear that events in the
      preceding months are usually much more important than those around birth. The
      term perinatal medicine has therefore been replaced by fetal medicine.

PMID- 8872341
TI  - Antimicrobial therapy: toward the future.
AB  - The relatively unsophisticated approaches at the beginnings of antimicrobial
      therapy development, although important at the time, have been replaced by ever
      more complex and ingenious methods as the medical profession and the
      pharmaceutical industries face up to the realities of the emerging problems of
      antimicrobial resistance.

PMID- 8872342
TI  - Management of suicidal risk.

PMID- 8872343
TI  - Psychiatry and the Health of the Nation: the view from the Department of Health.

PMID- 8872344
TI  - Caring for the elderly: problems and priorities.
AB  - In view of the projected massive increase in the number of the very aged, all
      health-care agencies, professionals and the government must develop an acceptable
      strategy of care. With a positive attitude towards aging based on facts and
      knowledge, the burden of such a demographic change can be minimized. Perhaps a
      dedicated government department or even a separate ministry may be useful.

PMID- 8872345
TI  - Mechanisms of carcinogenesis and molecular epidemiology.
AB  - Molecular epidemiology supplies information on various stages of the multistep
      process of carcinogenesis and allows identification of biological markers that
      may indicate an increased risk of cancer. These markers have an established
      position in occupational and environmental epidemiology.

PMID- 8872346
TI  - Promoting the Health of the Nation.
AB  - This article outlines the opportunities that the NHS has to contribute to the
      Government's health strategy The Health of the Nation, launched in 1992. The
      article also gives an overview of progress made towards achieving primary Health
      of the Nation targets.

PMID- 8872347
TI  - Paying the cost of living.

PMID- 8872348
TI  - Suramin--a powerful inhibitor of neural ecto-diadenosine polyphosphate hydrolase.
AB  - The neural ecto-diadenosine polyphosphate hydrolase (ecto-ApnAase) from plasma
      membranes of Torpedo synaptic terminals is inhibited by suramin. This study was
      carried out by discontinuous h.p.l.c. and continuous fluorometric methods. The
      concentration-dependence studies showed a non-competitive mechanism for suramin
      in the Dixon plot, with a Ki value of 1.79 +/- 0.03 microM with respect to
      epsilon-(Ap3A) as the substrate and 1.69 +/- 0.05 microM and 1.86 +/- 0.06 microM
      for epsilon-(Ap4A) and epsilon-(Ap5A) respectively. These results indicate that
      suramin could be a base compound inhibiting ecto-ApnAase and providing an
      alternative way of studying the pharmacology of diadenosine polyphosphate
      receptors.

PMID- 8872349
TI  - Prevention of vascular nitroglycerin tolerance by inhibition of protein kinase C.
AB  - We investigated whether in vivo inhibition of protein kinase C (PKC) can prevent
      the development of vascular tolerance and restore the sensitivity of isolated
      vessels to nitroglycerin (NTG). Tolerance was induced in male Wistar rats by a
      constant i.v. infusion of NTG 1 mg kg-1 h-1, a dose which did not alter blood
      pressure. After 72 h, the aorta was removed and the sensitivity of aortic rings
      to NTG tested. Chronic NTG infusion resulted in a 5.5 fold decrease in NTG
      sensitivity as compared with controls (vehicle), indicating the development of
      vascular tolerance. The simultaneous in vivo administration of the specific PKC
      inhibitor N-benzoyl-staurosporine (30 mg kg-1 day-1) prevented this decrease in
      NTG sensitivity. These results suggest a role for PKC activation in the
      development of vascular NTG tolerance.

PMID- 8872350
TI  - Capsinolol: the first beta-adrenoceptor blocker with an associated calcitonin
      gene-related peptide releasing activity in the heart.
AB  - 1. The beta-adrenoceptor blocking and calcitonin gene-related peptide (CGRP)
      releasing properties of capsinolol (N-[4-(2-hydroxy-3 (isopropylamino) propoxy)-3
      methoxybenzyl]-nonanamide), derived from nonivamide, were investigated under in
      vivo and in vitro conditions. 2. Capsinolol (0.1, 0.5, 1.0 mg kg-1, i.v.), as
      well as (+/-)-propranolol, produced a dose-dependent bradycardia response and a
      temporary pressor action in urethane-anaesthetized normotensive Wistar rats.
      These cardiovascular effects were different from the vagus reflex and
      parasympathetic efferent effects shown by capsaicin (0.1 mg kg-1, i.v.) in the
      rat. 3. Capsinolol (1.0 mg kg-1) inhibited the tachycardia effects induced by (-)
      isoprenaline, but had no blocking effect on the arterial pressor responses
      induced by (-)-phenylephrine. The findings suggest that capsinolol possesses beta
      adrenoceptor blocking activity, but it has no alpha-adrenoceptor blocking
      activity. 4. In guinea-pig isolated tissues, capsinolol (10(-8) to 10(-6) M)
      antagonized (-)-isoprenaline-induced positive chronotropic and inotropic effects
      of the atria and tracheal relaxation responses in a concentration-dependent
      manner. The parallel shift to the right of the concentration-response curve of (
      )-isoprenaline suggests capsinolol is a beta-adrenoceptor competitive antagonist.
      5. Capsinolol (10(-5) to 10(-4) M) exhibited a positive cardiotonic effect that
      was not inhibited by (+/-)-propranolol and reserpine, but was inhibited by
      capsazepine (10(-6) M) and CGRP8-37 (10(-6) M). This effect was independent of
      intrinsic sympathomimetic effects. 6. An immunoassay of released CGRP from guinea
      pig isolated perfused heart indicated that capsinolol increases the release of
      CGRP and thus produces positive cardiotonic effects. 7. In conclusion, capsinolol
      is a non-selective beta-adrenoceptor antagonist with capsaicin-like cardiotonic
      properties unrelated to traditional intrinsic sympathomimetic effects. It is
      suggested that capsinolol causes CGRP release from cardiac sensory neurones via a
      non-adrenergic mechanism and then activates CGRP receptors on cardiac muscle.

PMID- 8872351
TI  - Calphostin C-sensitive enhancements of force by lysophosphatidylinositol and
      diacylglycerols in mesenteric arteries from the rat.
AB  - 1. A pharmacological characterization was made of the effects of lysophosphatidyl
      inositol (lysoPI) and -ethanolamine (lysoPE) on the Ca(2+)-sensitivity of
      contraction in alpha-toxin permeabilized rat mesenteric arteries. The effect of
      GTP gamma S (G-protein activator), diacylglycerols (DAGs, dioctanoyl glycerol
      (diC8) and 1-stearoyl-2-arachidonoyl-sn-glycerol) and phorbol myristate acetate
      (PMA, protein kinase C (PKC) activator) on Ca(2+)-sensitivity was also assessed.
      2. LysoPI increased the Ca(2+)-sensitivity, demonstrated by both an increase in
      tension induced by 1 microM [Ca2+]free and an increase in the Ca(2+)-sensitivity
      of Ca2+ concentration-tension curves. LysoPE did not enhance force or Ca(2+)
      sensitivity. 3. GTP gamma S enhanced force at constant Ca2+, increased the Ca(2+)
      sensitivity, and increased force under Ca(2+)-free conditions. PMA also increased
      force at constant Ca2+ and increased Ca(2+)-sensitivity, but caused no force
      development under Ca(2+)-free conditions. 4. DAGs, both diC8 and the more
      physiological relevant DAG, 1-stearoyl-2-arachidonoyl-sn-glycerol, enhanced force
      at constant Ca2+ and increased the Ca(2+)-sensitivity. DiC8, in contrast to 1
      stearoyl-2-arachidonoyl-sn-glycerol, caused force development under Ca(2+)-free
      conditions and substantially enhanced force at maximal Ca(2+)-induced
      contraction. GDP-beta-S abolished the increased Ca(2+)-sensitization induced by
      noradrenaline, but not that by DAGs. 5. The PKC inhibitor calphostin C completely
      abolished Ca(2+)-sensitization induced by all of the Ca(2+)-sensitizing agents.
      6. These results show that lysoPI can increase the Ca(2+)-sensitivity of smooth
      muscle contraction, and the Ca(2+)-sensitization induced by DAGs was not
      completely G-protein mediated, because it was not inhibited by GDP-beta-S. A
      central role for PKC in regulation of Ca(2+)-sensitization in rat mesenteric
      small arteries was indicated by the abolishment of Ca(2+)-sensitization by
      calphostin C.

PMID- 8872352
TI  - Effects of S-ethylisothiourea, a potent inhibitor of nitric oxide synthase, alone
      or in combination with a nitric oxide donor in splanchnic artery occlusion shock.
AB  - 1. The aim of this study was to compare the effects of an intravenous infusion of
      a potent and non selective nitric oxide synthase inhibitor S-ethylisothiourea
      (Ethyl-TU) with that of a nitric oxide (NO) donor on the pathological sequelae
      associated with splanchnic artery occlusion (SAO) shock. In addition the effects
      of the combination of these two treatments were also investigated. 2. SAO shock
      was induced in anaesthetized rats by clamping splanchnic arteries for 45 min.
      Sham operated animals were used as controls. Survival time, white blood cell
      (WBC) count, mean arterial blood pressure, myeloperoxidase activity (MPO; studied
      as a quantitative means to evaluate neutrophil accumulation) and the
      responsiveness of aortic rings to acetylcholine (ACh, 10 nM-10 microM) and to
      phenylephrine (PE, 1 nM-10 microM) were studied. 3. SAO shocked rats had a
      decreased survival rate (0% survival 2 h after the release of occlusion) and
      survival time (76 +/- 10 min), increased MPO activity in the ileum (3.39 +/- 0.8
      u x 10(-3) g-1 tissue), a marked leukopenia and a profound hypotension. In
      addition aortic rings from shocked rats showed a marked hyporeactivity to PE and
      reduced responsiveness to ACh. Endothelium denuded aortic rings had also a marked
      hyporeactivity to PE. 4. In vivo administration of Ethyl-TU (0.1 mg kg-1 h-1,
      beginning 1 min after the onset of reperfusion) significantly increased survival
      time and rate, improved mean arterial blood pressure, restored the responsiveness
      to PE, but did not change MPO activity, leukopenia or the impairment in the
      responsiveness of aortic rings to ACh. Addition of Ethyl-TU (2 microM) to
      endothelium denuded aortic rings in vitro, restored the marked hyporeactivity to
      PE. Administration of the NO donor C87-3754 (0.75 mg kg-1 h-1, beginning 1 min
      after the onset of reperfusion) slightly increased survival time and reduced MPO
      activity and leukopenia, but did not change survival rate and mean arterial blood
      pressure. In addition C87-3754 restored the responsiveness of aortic rings to ACh
      to control values, but did not modify the hyporeactivity to PE. The combination
      of these two interventions produced a higher degree of protection than either
      Ethyl-TU or C87-3754 alone. In fact, co-administration of Ethyl-TU plus C87-3754
      completely prevented mortality, reduced MPO activity, attenuated leukopenia and
      the profound hypotension and restored the impaired responsiveness of aortic rings
      to PE and ACh. 5. Our study suggests that treatment with a nitric oxide synthase
      inhibitor combined with an NO donor may be a new therapeutic approach to the
      treatment of splanchnic artery occlusion shock.

PMID- 8872353
TI  - Influence of ACTH-(1-24) on free radical levels in the blood of haemorrhage
      shocked rats: direct ex vivo detection by electron spin resonance spectrometry.
AB  - 1. The influence of ACTH-(1-24) on the blood levels of highly reactive free
      radicals in haemorrhagic shock was studied in rats. 2. Volume-controlled
      haemorrhagic shock was produced in adult rats under general anaesthesia
      (urethane, 1.25 g kg-1 intraperitoneally) by stepwise bleeding until mean
      arterial pressure stabilized at 20-23 mmHg. Rats were intravenously (i.v.)
      treated with either ACTH-(1-24) (160 micrograms kg-1 in a volume of 1 ml kg-1) or
      equivolume saline. Free radicals were measured in arterial blood by electron spin
      resonance spectrometry using an ex vivo method that avoids injection of the spin
      trapping agent (alpha-phenyl-N-tert-butylnitrone). 3. Blood levels of free
      radicals were 6490 +/- 273 [arbitrary units (a.u.) ml-1 whole blood, before
      starting bleeding, and 30762 +/- 2650 after bleeding termination (means +/- s.e.
      mean of the values obtained in all experimental groups). All rats treated with
      saline died within 30 min, their blood levels of free radicals being 35450 +/-
      5450 a.u. ml-1 blood, 15 min after treatment. Treatment with ACTH-(1-24) produced
      a rapid and sustained restoration of arterial pressure, pulse pressure, heart
      rate and respiratory function, with 100% survival at the end of the observation
      period (2 h); this was associated with an impressive reduction in the blood
      levels of free radicals, that were 12807 +/- 2995, 10462 +/- 2850, 12294 +/-
      4120, and 10360 +/- 2080 a.u. ml-1 blood, 15, 30, 60 and 120 min after ACTH-(1
      24) administration, respectively. 4. These results provide a direct demonstration
      that (i) in haemorrhagic shock there is a rapid and massive production of highly
      reactive free radicals, and that (ii) the sustained restoration of cardiovascular
      and respiratory functions induced by the i.v. injection of ACTH-(1-24) is
      associated with a substantial reduction of free radical blood levels. It is
      suggested that ACTH-(1-24) prevents the burst of free radical generation during
      blood mobilisation and subsequent tissue reperfusion, and this may be an
      important component of its mechanism of action in effectively preventing death
      for haemorrhagic shock.

PMID- 8872354
TI  - Influence of the endothelium and nitric oxide on the contractile responses evoked
      by 5-HT1D receptor agonists in the rabbit isolated saphenous vein.
AB  - 1. We investigated whether contractile responses evoked by 5-HT1D receptor
      agonists were influenced by the endothelium (E) and nitric oxide (NO) in the
      rabbit isolated saphenous vein. 2. Saphenous vein rings were set up for isometric
      tension recording in oxygenated (5% CO2 in O2) Krebs solution (pH 7.4) containing
      (10(-6) M): idazoxan (1), indomethacin (10), ketanserin (0.1), prazosin (10), and
      N(omega) nitro-L-arginine methyl ester (L-NAME; 0 or 10), a NO synthase
      inhibitor. In some experiments, the E was removed mechanically. 3. 5
      Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and sumatriptan (Sum)
      contracted rabbit saphenous vein rings in the potency order (pD2 range) of 5
      CT(7.2-7.6) > 5-HT(6.2-7.1) > Sum(5.0-5.8), irrespective of the presence or
      absence of the E or L-NAME (n = 9-37 per group) indicating that the potencies of
      the 3 agonists were not significantly affected by either the E or L-NAME. 4.
      Efficacy, as assessed by the maximal contractile response (Emax), was
      significantly greater for Sum compared to 5-HT and 5-CT with intact E
      irrespective of the presence (77 +/- 3, 62 +/- 3, and 50 +/- 3 mN respectively; P
      < 0.05 Sum versus 5-HT and 5-CT) or absence (26 +/- 3, 14 +/- 4, and 13 +/- 2 mN
      respectively; P < 0.05 Sum versus 5-HT and 5-CT) of L-NAME. In E-denuded rings,
      the Emax values were all higher than in E-intact rings and did not differ between
      the 3 agonists (36 +/- 4, 37 +/- 4, and 36 +/- 5 mN for Sum, 5-HT and 5-CT,
      respectively; P > 0.5 between the 3 agonists) indicating that an endothelium
      derived relaxing factor (EDRF) counteracted the constrictor activities of the 5
      HT1D receptor agonists and raising the possibility that a component of the Sum
      induced contractile responses was E-dependent. Without E, the presence of L-NAME
      did not significantly affect the Emax values of the 3 agonists (41 +/- 4, 41 +/-
      5, and 41 +/- 4 mN for Sum, 5-HT, and 5-CT respectively; P > 0.5 between the 3
      agonists) indicating that the NO synthase inhibited was of endothelial origin. 5.
      Potentiation of the Emax of the 3 agonists by L-NAME was significantly albeit
      partially reversed by L-arginine (10(-2) M) indicating that NO synthase was
      indeed inhibited by L-NAME. Furthermore, in the presence of E, potentiation of
      Emax of the 3 agonists by L-NAME was mimicked by methylene blue (10(-5) M)
      providing further evidence that NO was involved in the attenuation by the E of
      the contractile responses induced by the 5-HT1D receptor agonists. 6. In the
      presence of an intact E and L-NAME, contractile responses elicited by 5-HT and
      Sum were competitively antagonized by the non-selective 5-HT1D receptor
      antagonist, methiothepin (pA2: 9.4 and 8.8; slopes: 0.66 and 0.81, respectively)
      and the highly selective 5-HT1D receptor antagonist, GR 127935 (pA2: 9.0 in each
      case; slopes: 1.04 and 0.93, respectively) indicating that contractions were
      mediated through activation of a single population of 5-HT1D receptors.
      Contractile responses elicited by 5-CT were also competitively antagonized by
      methiothepin and GR 127935, but non parallel rightward shifts of the
      concentration-response curves were observed suggestive of the involvement of
      additional but as yet unidentified receptors in mediating the 5-CT-induced
      responses. 7. In conclusion, the efficacy, but not the potency, of 5-HT, 5-CT and
      Sum in evoking 5-HT1D receptor-mediated contractile responses are subject to a
      substantial inhibitory influence of the E and of an EDRF (probably NO).

PMID- 8872355
TI  - Investigation of the negative inotropic effects of 17 beta-oestradiol in human
      isolated myocardial tissues.
AB  - 1. The aim of the present study was to evaluate the effects of 17 beta-oestradiol
      in human myocardium. The effects of 17 beta-oestradiol, progesterone and
      testosterone on force of contraction were investigated in electrically driven
      isolated atrial trabeculae and ventricular papillary muscles from human hearts in
      the presence and absence of Bay K 8644, a calcium channel agonist. In addition,
      the effects of 17 beta-oestradiol, progesterone and testosterone on binding of
      [3H]-PN 200 110 were assessed in membranes prepared from human ventricular
      myocardium. 2. 17 beta-Oestradiol elicited a negative inotropic effect in atrial
      (IC50: 7.1 mumol 1(-1), confidence interval 3.8 to 13.4, n = 3) and ventricular
      preparations (IC50: 4.6 mumol 1(-1)), confidence interval 2.2 to 9.4, n = 3) as
      compared with solvent controls. There was no significant difference (P > 0.05) of
      IC50 values in the absence and presence of isoprenaline (0.0 mumol 1(-1)) in
      atrial (IC50: 10.8 mumol 1(-1), confidence interval 9.1 to 12.9, n = 6) and
      ventricular preparations (IC50: 9.4 mumol 1(-1), confidence interval 7.3 to 11.9,
      n = 8). 3. 17 beta-Oestradiol at 30 mumol 1(-1) induced a significant rightward
      shift of the concentration-response curves for the positive inotropic effect of
      Bay K 8644 in atrial preparations (EC50: 0.13 mumol 1(-1), confidence interval
      0.08 to 0.19, n = 6; EC50 with 17 beta-oestradiol: 0.58 mumol 1(-1), confidence
      interval 0.33 to 0.83, n = 6, P < 0.05) and ventricular preparations (EC50: 0.07
      mumol 1(-1), confidence interval 0.04 to 0.11, n = 8; EC50 with 17 beta
      oestradiol: 0.3 mumol 1(-1), confidence interval 0.18 to 0.49, n = 8, P < 0.05).
      Testosterone, progesterone at 30 mumol 1(-1) and the solvent control had no
      significant effect on the concentration-response curves to Bay K 8644. 4. In
      membranes prepared from human ventricular myocardium the effect of 17 beta
      oestradiol on binding of [3H]-PN 200 110, an antagonist at the 1,4
      dihydropyridine binding site, was not different from that observed with
      progesterone, testosterone or solvent controls. 5. In myocardial membranes no
      specific oestrogen receptors were demonstrated by [3H]-oestradiol binding
      studies. 6. Thus, the calcium antagonistic property of 17 beta-oestradiol cannot
      be attributed to a direct interaction with 1, 4 dihydropyridine binding sites.

PMID- 8872356
TI  - Effects of N-, P- and Q-type neuronal calcium channel antagonists on mammalian
      peripheral neurotransmission.
AB  - 1. The effects of N-, P- and Q-type neuronal voltage-operated calcium (Ca2+)
      channel antagonists on neurotransmission were determined in a range of
      cardiovascular and urogenital tissues, as well as the diaphragm, isolated from
      rat or mouse. 2. The pharmacological tools chosen were omega-conotoxin GVIA (CTX
      GVIA), a selective N-type Ca2+ channel antagonist, the P-type channel blocker (<
      or = 100 nM) omega-agatoxin IVA (AGA IVA) and omega-conotoxin MVIIC (CTX MVIIC),
      a non-selective antagonist of N-, P- and Q-type channels. The effects of these
      antagonists on nerve-mediated responses were assessed in right atria, vasa
      deferentia, phrenic nerve-hemidiaphragms and small mesenteric arteries. 3. Rat
      mesenteric artery contractile responses to perivascular nerve stimulation were
      concentration-dependently inhibited by CTX GVIA (1-10 nM); inhibition was 92%
      with 10 nM. CTX MVIIC was > 100 fold less potent and only caused an inhibition of
      46% at the highest concentration (1000 nM). AGA IVA (100 nM) had no effect. 4. In
      rat vas deferens stimulated at 0.05 Hz, CTX GVIA (10 nM) completely inhibited the
      twitch response and CTX MVIIC, about 100 fold less potent, caused total
      inhibition at 1000 nM. AGA IVA did not affect the twitch. In rat preparations
      stimulated at 20 Hz, a CTX GVIA-resistant (< or = 1000 nM) twitch response of 25%
      was apparent which could be blocked by 1000 nM AGA IVA or CTX MVIIC. In mouse vas
      deferens (20 Hz stimulation), CTX GVIA 10 nM caused an 87% inhibition of the
      twitch, the remainder being resistant to CTX GVIA, 100 nM. CTX MVIIC was only 10
      fold less potent than CTX GVIA and completely inhibited the response at 1000 nM.
      AGA IVA (100 nM) inhibited the twitch by 55%. 5. The twitch response of the mouse
      phrenic nerve-hemidiaphragm was concentration-dependently inhibited by AGA IVA (1
      100 nM); inhibition was 92% at 100 nM. CTX MVIIC was about 10 fold less potent
      than AGA IVA with an inhibition of 80% at 1000 nM. CTX GVIA was without effect.
      In the rat diaphragm preparation, AGA IVA (< or = 100 nM) and CTX GVIA (< or =
      1000 nM) had little effect on the twitch response. CTX MVIIC (1000 nM) inhibited
      the twitch by 57%. 6. In rat and mouse right atria, sympathetic responses were
      concentration-dependently inhibited by CTX GVIA with almost complete block at 10
      100 nM. CTX MVIIC was 100 fold less potent and caused complete inhibition at 1000
      nM in the mouse preparation. AGA IVA did not affect atrial sympathetic responses.
      7. These data suggest that N-type Ca2+ channels predominate in the control of
      sympathetic transmission in the mesenteric artery, vas deferens and right atrium.
      In the mouse vas deferens (and rat tissue at high stimulus frequency), P- and Q
      type channels also mediate Ca2+ influx. P- and Q-type Ca2+ channels control
      neurosecretion at the motor endplate, with no role for N type channels.

PMID- 8872357
TI  - Glomerular filtration and saturable absorption of iohexol in the rat isolated
      perfused kidney.
AB  - 1. The renal handling of iohexol was examined in the rat isolated perfused kidney
      (IPK) over a perfusate concentration range of 5-20 micrograms ml-1. 2. At a
      concentration of 5 micrograms ml-1, a ratio of renal clearance over clearance by
      glomerular filtration (ClR/GF) of 0.63 +/- 0.06 could be determined. This ratio
      increased until 1.02 +/- 0.06 at 20 micrograms ml-1, indicating that a saturable
      mechanism is involved in the luminal disappearance of the drug. 3. Pretreatment
      of the kidneys with polylysine, probenecid or diatrizoate resulted in a
      significantly enhanced clearance of iohexol, probably due to inhibition of
      membrane binding. Renal clearance data were fitted to a kinetic model including
      filtration into the primary urine followed by saturable absorption at the luminal
      membrane. An absorption constant, KA, of 7.3 +/- 1.3 micrograms ml-1, and a
      maximum rate of absorption, VA,Max, of 1.4 +/- 0.1 micrograms min-1 were
      determined. 4. Iohexol accumulated in kidney tissue, reaching a concentration of
      2 to 7.5 times the perfusate concentration. In freshly isolated proximal tubular
      cells and kidney cortex mitochondria, iohexol reduced the uncoupled respiratory
      rate at a concentration comparable to the highest tissue concentration found in
      the IPK. 5. In conclusion, iohexol is not only filtered by the kidney but also
      reabsorbed via a saturable mechanism, which results in tubular accumulation.
      Intracellularly sequestered iohexol may affect mitochondrial oxidative
      metabolism. Our results indicate that iohexol is not a true filtration marker.

PMID- 8872358
TI  - Differentiation of sigma ligand-activated receptor subtypes that modulate NMDA
      evoked [3H]-noradrenaline release in rat hippocampal slices.
AB  - 1. It is now widely accepted that there are two classes of sigma (sigma) binding
      sites, denoted sigma(1) and sigma(2), and recently sigma(3) subtype has been
      proposed. Selective sigma(1) and sigma(2) receptor agonists are known to modulate
      the neuronal response to N-methyl-D-aspartate (NMDA) in vivo and in vitro. To
      identify the site of action of a series of recently synthesised high affinity
      sigma ligands, the present in vitro series of experiments was carried out on NMDA
      evoked [3H]-noradrenaline ([3H]-NA) overflow from preloaded hippocampal slices of
      the rat. 2. The ligands (+)-cis-N-methyl-N-[2,(3,4-dichlorophenyl) ethyl]-2-(1
      pyrrolidinyl) cyclohexylamine (BD-737) and (+)-pentazocine, considered as the
      prototypic sigma(1) agonists, potentiated the NMDA response from 10 nM to 100 nM.
      This potentiation faded between 100 nM and 1 microM ligand concentrations. On the
      other hand, 1,3-di(2-tolyl)guanidine (DTG), a mixed sigma(1)/sigma(2) agonist, at
      concentrations greater than 100 nM inhibited the NMDA-evoked [3H]-NA release.
      Spiperone, considered as active on putative sigma(3) receptors, was without
      effect on the NMDA response, or on the potentiating effect of BD-737. 3. The high
      affinity sigma antagonists haloperidol and 1[2-(3,4-dichlorophenyl)ethyl]-4
      methylpiperazine (BD-1063), inactive by themselves on the NMDA-induced response,
      at concentrations above 30 nM totally prevented the potentiating effect of (+)
      pentazocine (100 nM) as well as the inhibitory effect of DTG (300 nM) on NMDA
      evoked [3H]-NA release. Whereas haloperidol and BD-1063, at concentrations < 1
      microM, were inactive on the potentiating effect of BD-737 (100 nM). 4. 4-(4
      Chlorophenyl)-alpha-4-fluorophenyl-4-hydroxy-1-piperidinebutanol (reduced
      haloperidol), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1
      pyrrolidinyl)ethylamine (BD-1008), inactive by themselves on the NMDA-evoked [3H]
      NA release, failed to reverse the effects of (+)-pentazocine and DTG, but at
      concentrations of 30 nM to 1 microM antagonised the BD-737-induced potentiation
      of the NMDA response. Conversely, N,N-dipropyl-2-[4-methoxy-3-(2
      phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) blocked the effects of
      (+)-pentazocine as well as those of BD-737, but not those of DTG. 5. The present
      results provide in vitro functional evidence for a sigma receptor type
      preferentially sensitive to BD-737, reduced haloperidol, BD-1008 and also to NE
      100, that differs from the already identified sigma(1), sigma(2) and sigma(3)
      sites.

PMID- 8872359
TI  - Effects of sigma ligands on the cloned mu-, delta- and kappa-opioid receptors co
      expressed with G-protein-activated K+ (GIRK) channel in Xenopus oocytes.
AB  - 1. Taking advantage of the functional coupling of the opioid receptors with the G
      protein-activated K+ (GIRK) channel, we investigated the effects of sigma (sigma)
      ligands of various structural and pharmacological classes, (+)-N
      allylnormetazocine ((+)-SKF10047) and (+)-cyclazocine, (+)-3-(3-hydroxyphenyl)-N
      (1-propyl)piperidine ((+)-3PPP), 1,3-di-(2-tolyl)guanidine (DTG), carbetapentane
      and haloperidol, on the inward K+ current responses in Xenopus oocytes co
      injected with each of the cloned mu-, delta- and kappa-opioid receptor mRNAs and
      the GIRK1 mRNA. 2. (+)-SKF10047 acted as a delta- and kappa-agonist (EC50 values
      (microM) = 0.618 and 0.652, respectively) and mu-antagonist (IC50 value (microM)
      = 8.51). (+)-Cyclazocine acted as a kappa-agonist and mu-antagonist (IC50 =
      33.2). (+)-3PPP acted as a kappa-agonist (EC50 = 18.08 and a mu-antagonist. DTG
      acted as a mu- and kappa-agonist (EC50 = more than 30 and 14.88, respectively).
      Carbetapentane acted as a kappa-agonist and mu-antagonist (IC50 = 11.2).
      Haloperidol acted as a mu- and delta-agonist (EC50 = 5.683 and 7.389,
      respectively). 3. All currents induced by sigma ligands were reduced by 1 microM
      naloxone, an opioid receptor antagonist, and blocked by 300 microM Ba2+, a GIRK
      channel blocker. It was also indicated that the antagonism by naloxone at the
      delta-- and kappa-opioid receptors was weaker than that of naloxone at the mu
      opioid receptor. The sigma ligands tested had no effect on the current responses
      in the oocytes injected with each of the opioid receptor mRNAs alone or with the
      GIRK1 mRNA alone. 4. We conclude that various sigma ligands directly interact
      with the cloned mu-, delta- and kappa-opioid receptors in Xenopus oocytes. Our
      results suggest that the effects of the sigma ligands may be partly mediated by
      the opioid receptors.

PMID- 8872360
TI  - Effect of capsaicin and analogues on potassium and calcium currents and vanilloid
      receptors in Xenopus embryo spinal neurones.
AB  - 1. The potassium current in embryo spinal neurones of Xenopus consists of at
      least two kinetically distinct components with overlapping voltage-dependencies
      of activation. We investigated whether capsaicin might specifically block these
      components in acutely dissociated neurones from stage 37/38 embryos by use of
      standard patch clamp techniques. 2. Capsaicin caused a time-dependent block of
      both the slow and fast components of the potassium current. The concentration
      dependence was described by the Hill equation with a KD of 21 microM and a
      coefficient of 1.5 (n = 9-11 at each concentration). Differences between the
      observed and fitted values were not significant at the 5% level (chi(2) = 2.80, 6
      degrees of freedom). 3. Capsaicin did not affect the time course or voltage
      sensitivity of activation, but the steady-state block was voltage-dependent. The
      block could be relieved by hyperpolarization, and the rate of the removal of
      block was voltage- and time-dependent. The time constant for the blocking
      reaction was also voltage-dependent for voltage steps below +30 mV, but above
      this level it was voltage-independent. These results suggest that capsaicin
      blocks potassium channels by an open channel mechanism. 4. Other derivatives of
      vanillin, such as capsazepine, resiniferatoxin, and piperine also blocked
      potassium channels. Capsazepine and resiniferatoxin caused a greater block than
      similar concentrations of capsaicin, and in the case of capsazepine, the block
      was also clearly time-dependent. 5. Capsaicin and capsazepine also blocked
      calcium currents in a time-dependent manner. Fitting the Hill equation to the
      averaged data gave a KD of 43.5 microM, and a coefficient of 1.35 (n = 11 at each
      concentration). The fitted values were not significantly different from the
      observed means at the 5% level (chi(2) = 12.1, 6 degrees of freedom). 6. Six out
      of 29 Rohon-Beard sensory neurones responded to capsaicin with an inward current
      that appeared to be similar to the capsaicin activation of mammalian C sensory
      neurones. This response saturated at 10 microM capsaicin.

PMID- 8872361
TI  - Adrenoceptor- and cholinoceptor-mediated mechanisms in the regulation of 5
      hydroxytryptamine release from isolated tracheae of newborn rabbits.
AB  - 1. Isolated tracheae of newborn rabbits were incubated in vitro and the outflow
      of 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. with electrochemical
      detection. Evidence has previously been provided that this 5-HT outflow derives
      from neuroendocrine epithelial (NEE) cells of the airway mucosa. 2. Phenylephrine
      (1, 10 and 30 microM) enhanced the outflow of 5-HT by 80, 290 and 205%,
      respectively. 5-HT outflow evoked by 10 microM phenylephrine was not affected by
      the presence of the neurotoxin tetrodotoxin (1 microM). 3. Rauwolscine, ARC 239
      (an alpha(2B)-adrenoceptor preferring antagonist), yohimbine and prazosin
      antagonized the effect of 10 microM phenylephrine in a concentration-dependent
      manner with IC50 values of 150, 295, 300 and 1,700 nM, respectively. Comparison
      of the ratios (between all antagonists) of the present IC50 values with the
      corresponding ratios of Ki values obtained in binding studies for the alpha(2A)-,
      alpha(2B)-, alpha(2C)- and alpha(2D)-adrenoceptor subtypes strongly suggests the
      involvement of an alpha(2B)-receptor. 4. 5-HT outflow evoked by 10 microM
      phenylephrine was inhibited by 65% in the presence of 1 microM forskolin and
      abolished in the presence of 10 microM forskolin. 5. 5-HT outflow evoked by 10
      microM phenylephrine was inhibited by about 45 and 70% in the presence of 0.1 and
      1 microM isoprenaline, respectively. The inhibitory effect of 1 microM
      isoprenaline was only marginally antagonized by 1 microM, but blocked by 10
      microM propranolol. 6. 5-HT outflow was not affected by the muscarine receptor
      agonist oxotremorine (10 microM), but was enhanced by 175% by 100 microM
      nicotine. The effect of nicotine was blocked by 100 microM hexamethonium and
      prevented by 1 microM tetrodotoxin or 1 microM yohimbine. 7. In conclusion, 5-HT
      release from NEE cells of the rabbit trachea is stimulated via alpha
      adrenoceptors most likely of the alpha(2B)-subtype localized directly at the NEE
      cells. Activation of beta-adrenoceptors as well as direct activation of adenylyl
      cyclase by forskolin exert inhibitory effects on 5-HT release. Activation of
      nicotinic, but not of muscarinic receptors, also evokes the release of 5-HT.
      However, the effect of nicotine appears to be mediated indirectly via the release
      of noradrenaline.

PMID- 8872363
TI  - Physiological and behavioural effects of the endogenous cannabinoid,
      arachidonylethanolamide (anandamide), in the rat.
AB  - 1. Arachidonylethanolamide (AEA; anandamide) has been isolated from mammalian
      brain and found to bind to, and is thought to be, an endogenous ligand for the
      cannabinoid receptor. In order to understand better its behavioural and
      physiological properties, we have examined its acute effects in unanaesthetized
      freely behaving rats. 2. Intravenous AEA caused dose-related decreases in
      locomotor behaviour, a pronounced hyperreflexia, and a moderate antinociceptive
      state. At doses between 3 and 30 mg kg-1, a dose-dependent hypothermia and
      profound, time-dependent cardiovascular changes were also observed. 3. An
      immediate bradycardia exceeding 50% was seen within 10-15 s of administration and
      lasted up to 11 min following the highest dose of the drug. In contrast, the
      change in mean arterial pressure was biphasic: an immediate 20% decrease in mean
      arterial pressure followed by a significant increase in blood pressure that
      lasted about 13 min after the highest dose. 4. These data demonstrate that AEA in
      the unanaesthetized rat exerts behavioural and physiological effects generally
      similar to those seen following natural cannabinoids and synthetic cannabimimetic
      agents and suggests a role for AEA in regulation of various physiological
      processes.

PMID- 8872362
TI  - Effects of SCA40 on human isolated bronchus and human polymorphonuclear
      leukocytes: comparison with rolipram, SKF94120 and levcromakalim.
AB  - 1. SCA40 (0.1 nM-0.1 mM) produced concentration-dependent suppression of the
      spontaneous tone of human isolated bronchus (-log EC50 = 6.85 +/- 0.09; n = 10)
      and reached a maximal relaxation similar to that of theophylline (3 mM). The
      potency (-log EC50 values) of SCA40 compared to other relaxants was rolipram
      (7.44 +/- 0.12; n = 9) > SCA40 > or = levcromakalim (6.49 +/- 0.04; n = 6) >
      SKF94120 (5.87 +/- 0.10; n = 9). 2. When tested against the activity of the
      isoenzymes of cyclic nucleotide phosphodiesterase (PDE) isolated from human
      bronchus, SCA40 proved highly potent against PDE III (-log IC50 = 6.47 +/- 0.16;
      n = 4). It was markedly less potent against PDE IV (4.82 +/- 0.18; n = 4) and PDE
      V (4.32 +/- 0.11; n = 4). 3. Human polymorphonuclear leukocytes (PMNs) stimulated
      with N-formylmethionyl-leucyl-phenylalanine (FMLP) produced a concentration
      dependent superoxide anion generation and elastase release. SCA40 (1 nM-10
      microM) produced a concentration-related inhibition of FMLP (30 nM approximately
      EC50)-induced superoxide production (-log IC50 = 5.48 +/- 0.10; n = 6) and
      elastase release (-log IC50 = 5.50 +/- 0.26; n = 6). Rolipram was an effective
      inhibitor of superoxide generation and elastase release (-log IC50 values
      approximately 8) while SKF94120 and levcromakalim were scarcely effective. 4.
      FMLP (30 nM) and thimerosal (20 microM) induced leukotriene B4 production and
      elevation of intracellular calcium concentration in human PMNs. The production of
      leukotriene B4 was inhibited by SCA40 in a concentration-related manner (-log
      IC50 = 5.94 +/- 0.22; n = 6) but SCA40 was less effective against the elevation
      of intracellular calcium. Rolipram was an effective inhibitor of leukotriene B4
      synthesis (-log IC50 approximately 7) and intracellular calcium elevation (-log
      IC50 approximately 6) while SKF94120 and levcromakalim were scarcely effective.
      5. It is concluded that SCA40 is an effective inhibitor of the inherent tone of
      human isolated bronchus. The bronchodilatation produced by SCA40 appears mainly
      related to PDE inhibition since the potency of SCA40 as a relaxant of human
      isolated bronchus was found to be close to its potency as inhibitor of PDE III
      activity isolated from human bronchus. In addition, SCA40 exhibited inhibitory
      effects on human PMN function stimulated by FMLP. These effects may be related to
      the ability of SCA40 to inhibit PDE IV from human PMNs while the contribution of
      PDE V inhibition is uncertain. We found no evidence of a role for levcromakalim
      sensitive plasmalemmal K+-channels in human PMNs.

PMID- 8872364
TI  - The structural requirements for phorbol esters to enhance noradrenaline and
      dopamine release from rat brain cortex.
AB  - 1. The effects of various protein kinase C (PKC) activators on the stimulation
      induced (S-I) release of noradrenaline and dopamine was studied in rat cortical
      slices pre-incubated with [3H]-noradrenaline or [3H]-dopamine. The aim was to
      investigate a possible structure-activity relationship for these agents on
      transmitter release. 2. 4 beta-Phorbol 12,13-dibutyrate (4 beta PDB, 0.1-3.0
      microM), enhanced S-I noradrenaline and dopamine release in a concentration
      dependent manner whereas the structurally related inactive isomer 4 alpha-phorbol
      12, 13-dibutyrate (4 alpha PDB, 0.1-3.0 microM) and phorbol 13-acetate (PA, 0.1
      3.0microM) were without effect on noradrednaline release. Another group of
      phorbol 12, 13-diesters containing a common 13-ester substituent (phorbol 12, 13
      diacetate, PDA, 0.1-3.0 microM; phorbol 12-myristate 13-acetate, PMA, 0.1-3.0
      microM; phorbol 12-methylaminobenzoate 13-acetate, PMBA, 0.03-3.0 microM) also
      enhanced S-I noradrenaline and dopamine release in a concentration-dependent
      manner with PMA being the least potent. 3. The 12-deoxyphorbol 13-substituted
      monoesters, 12-deoxyphorbol 13-acetate (dPA, 0.1-3.0 microM), 12-deoxyphorbol 13
      angelate (dPAng, 0.1-3.0 microM), 12-deoxyphorbol 13-isobutyrate (dPiB, 0.03-3.0
      microM) and 12-deoxyphorbol 13-phenylacetate (dPPhen, 0.1-3.0 microM) enhanced S
      I noradrenaline and dopamine release in a concentration-dependent manner. In
      contrast, 12-deoxyphorbol 13-tetradecanoate (dPT, 0.1-3.0 microM) was without
      effect. 4. The involvement of PKC in mediating the effects of the various phorbol
      esters was further investigated. PKC was down-regulated by 20 h exposure of the
      cortical slices to 4 beta-phorbol 12,13-dibutyrate (1 microM). In this case the
      facilitatory effect of 4 beta PDB and dPA was abolished whilst that of dPAng was
      significantly attenuated. This indicates that these agents were acting
      selectively at PKC. In support of this the PKC inhibitors, polymyxin B (21
      microM) and bisindolylmaleimide I (3 microM), attenuated the facilitatory effect
      of 4 beta PDB and dPAng although that of dPA was not significantly altered. 5.
      The effects of these agents on transmitter release were not correlated with their
      in vitro affinity and isozyme selectivity for PKC. Short chain substituted mono-
      and diesters of phorbol were more potent enhancers of action-potential evoked
      noradrenaline and dopamine release than the long chain esters. Interestingly,
      these former agents are the least potent or non effective (e.g. dPA, PDA) tumour
      promoters. We suggest that the reason for the poor effects of lipophilic long
      chain phorbol esters (PMA, dPT) on transmitter release is that they are
      sequestered in the plasmalemma and do not access the cell cytoplasm where the PKC
      may be located.

PMID- 8872365
TI  - The effects of the muscle relaxant, CS-722, on synaptic activity of cultured
      neurones.
AB  - 1. The pharmacological properties of the centrally acting muscle relaxant, CS
      722, were studied in cultured hippocampal cells and dorsal root ganglion cells of
      the rat using the whole-cell variation of the patch clamp technique. 2. CS-722
      inhibited the occurrence of spontaneous excitatory and inhibitory postsynaptic
      currents in hippocampal neurones at concentrations of 100-300 microM, but had no
      effect on postsynaptic currents evoked by the application of glycine, gamma
      aminobutyric acid, glutamate or N-methyl-D-aspartate. 3. CS-722 reduced voltage
      gated sodium currents, while shifting the sodium channel inactivation curve to
      more negative membrane potentials. This effect is similar to that reported for
      local anaesthetics. Voltage-gated potassium currents were decreased by CS-722 by
      approximately 20%, whereas voltage-activated calcium currents were inhibited by
      about 25%. 4. CS-722 inhibited evoked inhibitory postsynaptic currents. However,
      the spontaneous quantal release of inhibitory transmitter was not affected. 5.
      The inhibitory effect of CS-722 on spontaneous inhibitory postsynaptic currents
      and excitatory postsynaptic currents in hippocampal cultures probably results
      from an inhibition of both sodium and calcium currents. This inhibitory effect is
      likely to be amplified in polysynaptic neuronal circuits.

PMID- 8872366
TI  - Effects of class III antiarrhythmic drugs on the Na(+)-activated K+ channels in
      guinea-pig ventricular cells.
AB  - 1. Class III antiarrhythmic drugs are known to block the outward currents through
      voltage-gated K+ channels. However, effects of class III antiarrhythmic drugs on
      the ligand-gated K+ channels have not been thoroughly examined. In this study
      effects of amiodarone and newer class III antiarrhythmic drugs, E-4031 and MS
      551, on the Na+-activated K+ (KNa) current were examined in inside-out membrane
      patches and in whole cells isolated from guinea-pig ventricle. 2. The KNa channel
      current was activated by increasing [Na+]i from 0 mM to 30-100 mM with 150 mM
      [K+]o in inside-out membrane patches of ventricular myocytes. The channel current
      showed a larger slope conductance (210 pS), inward-going rectification and
      subconductance levels of various amplitudes. 3. E-4031 and MS-551 at high
      concentrations (300 microM) inhibited the K+ current by decreasing the open time
      (flickering block). On the other hand, amiodarone at relatively low
      concentrations (0.1-10 microM) inhibited the KNa channel current by decreasing
      the open probability rather than by decreasing the open time. The IC50 value of
      amiodarone for inhibiting the KNa channel current was 1.0 microM. 4. These drugs
      also inhibited the whole-cell outward current activated by intracellular loading
      of 50 mM [Na+]i and extracellular application of 10 microM ouabain. 5. These
      results indicate that class III antiarrhythmic drugs inhibit the KNa channel
      current in cardiac cells. However, there are sharp differences in the effective
      concentrations and the mode of inhibition between amiodarone and the newer class
      III antiarrhythmic drugs.

PMID- 8872367
TI  - The effect of L-type calcium channel modulators on the mobilization of
      intracellular calcium stores in guinea-pig intestinal smooth muscle.
AB  - 1. The action of Ca2+ channel modulators has been examined on the intracellular
      Ca2+ signal in the longitudinal smooth muscle cells of the guinea-pig intestine
      after exposure to histamine and to agents known to affect intracellular Ca2+
      stores. Isometric contraction has been measured simultaneously with front-surface
      fluorometry of fura 2-loaded preparations. 2. Histamine (10 microM) evoked a
      phasic and tonic increase in [Ca2+]i and contraction which were both sensitive to
      the Ca2+ channel blockers, nimodipine and D600. 3. Caffeine (10 mM) evoked in
      rapid increase in [Ca2+]i which was sustained as long as the preparation was
      exposed to the drug, whereas the contractile response was only phasic. In the
      presence of nimodipine 1 microM, the phasic contraction was absent although the
      fura 2-Ca2+ signal amounted to 32% of the control. 4. Ryanodine (10 microM)
      evoked a slow increase in [Ca2+]i and a contraction, both of which were reversed
      after exposure to nimodipine (1 microM) or D600 (10 microM). In the presence of
      diazoxide (500 microM), a hyperpolarizing agent, the ryanodine-evoked increase in
      [Ca2+]i and in muscle tone were inhibited. 5. Thapsigargin (1 microM) also
      produced an increase in [Ca2+]i and a contraction both of which were blocked by
      nimodipine (1 microM). 6. In Ca2+-free solution, histamine 10 microM evoked non
      reproducible phasic Ca2+ signal and contraction. This response was recovered
      after refilling in Ca2+ containing solution. The recovery was blocked by
      nimodipine, D600 or diazoxide and was facilitated by the Ca2+ channel activator,
      Bay K 8644. When the refilling medium was supplemented with thapsigargin, the
      recovered response was significantly reduced, but Bay K 8644 still had some
      action. 7. The present results show that blockage of L-type Ca2+ channels
      inhibited changes in [Ca2+]i evoked by histamine, caffeine and ryanodine which
      are generally attributed to Ca2+ mobilization from intracellular stores. They
      also show that when the tissue was exposed to nimodipine, D600 and diazoxide
      during the procedure of refilling after depletion of intracellular stores, the
      action of histamine on [Ca2+]i and contraction was blocked. Bay K 8644 had an
      opposite effect even when the Ca2+ pumping activity of the sarcoplasmic reticulum
      was reduced by thapsigargin. This indicates that refilling of intracellular Ca2+
      stores depleted by histamine in guinea-pig intestine mainly occurred through L
      type Ca2+ channels.

PMID- 8872368
TI  - M1 and M3 muscarinic receptors in human pulmonary arteries.
AB  - 1. Acetylcholine (ACh) and the M1 agonists (McN-A-343 or PD142505) relaxed human
      isolated pulmonary arteries which were pre-contracted with noradrenaline (10
      microM). In preparations where the endothelium had been removed ACh induced a
      contractile response whereas the M1 agonists (McN-A-343 or PD142505) had no
      effect. 2. ACh- and McN-A-343-induced relaxations were abolished after treatment
      of endothelium-intact preparations with the drug combination NG-nitro-L-arginine
      (L-NOARG: 0.1 mM) and indomethacin (1.7 microM). 3. The affinity (pKB value) for
      pirenzepine was higher in human pulmonary arteries when tissues were relaxed with
      McN-A-343 as compared with ACh (pKB values, 7.71 +/- 0.30 (n = 4) and 6.68 +/-
      0.15 (n = 8), respectively). In addition, the affinity for pFHHSiD against McN-A
      343- and ACh-induced relaxations was 6.86 +/- 0.13 (n = 3) and 7.35 +/- 0.11 (n =
      9) respectively. 4. The low affinities for methoctramine in human isolated
      pulmonary arteries with the endothelium either intact or removed, suggested the
      lack of involvement of M2 and M4 receptors in the Ach responses. 5.
      Phenoxybenzamine (3 microM: 30 min) abolished both ACh contraction and relaxation
      in human pulmonary artery. The ACh contraction was present when the
      phenoxybenzamine treatment was preceded by incubation with pFHHSiD (2 microM) but
      not with pirenzepine (1 microM). In addition, the ACh relaxation was present when
      preparations were treated with either pFHHSiD (2 microM) or pirenzepine (1
      microM), before exposure to phenoxybenzamine. 6. These results in human isolated
      pulmonary arteries support the notion that only M3 receptors, on smooth muscle,
      mediate the ACh-induced contraction whereas M3 and M1 receptors are involved in
      the endothelium-dependent ACh-induced relaxation.

PMID- 8872369
TI  - Functional evidence of inverse agonism in vascular smooth muscle.
AB  - 1. In the present study, depletion of internal Ca2+ stores sensitive to
      noradrenaline (1 microM) in rat aorta, is the signal for the entry of
      extracellular Ca2+, not only to refill the stores but also, in our experimental
      conditions, to activate the contractile proteins. This induces an increase in the
      resting tone that constitutes, the first functional evidence of this Ca2+ entry.
      2. The fact that methoxamine (100 microM) reproduces the same processes as
      noradrenaline but clonidine (1 microM) does not, indicates that alpha(1)
      adrenoceptor activation is related to the increase in the resting tone observed
      after depletion of adrenoceptor-sensitive internal Ca2+-stores. 3. Benoxathian
      and WB 4101 (alpha(1A)- and alpha(1D)-adrenoceptor antagonists) selectively
      inhibit, in a concentration-dependent manner, this mechanical response observed
      in absence of the agonist, which suggests that these agents can act as inverse
      agonists and provide a functional model for studying this phenomenon. Since
      chloroethylclonidine (100 microM) has no effect on this response, the
      participation of alpha(1B)-adrenoceptors can be ruled out. 4. Contractile
      responses to noradrenaline (1 microM) in Ca2+-free medium were selectively
      blocked by chloroethylclonidine. This suggests that the response to noradrenaline
      in Ca2+-free medium mainly depends on the activation of the alpha(1B)
      adrenoceptor subtype.

PMID- 8872370
TI  - Anticonvulsant effects of 7-nitroindazole in rodents with reflex epilepsy may
      result from L-arginine accumulation or a reduction in nitric oxide or L
      citrulline formation.
AB  - 1. To investigate the role of nitric oxide in epilepsy we have studied the
      effects of agents which affect nitric oxide synthesis in sound-induced seizures
      in DBA/2 mice and in genetically epilepsy-prone (GEP) rats. 2. The neuronal
      selective nitric oxide synthase inhibitor, 7-nitroindazole (7-NI) is
      anticonvulsant in these models with ED50 values against clonic seizures in mg kg
      1 i.p. (times following injection) of: 74 (+0.25 h), 120 (+1 h) in DAB/2 mice,
      and 56 (+0.25 h), 42 (+0.5 h), 36 (+1 h), 28 (+2 h), 38 (+4 h), 93 (+8 h) in GEP
      rats. 3. Therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) for 7
      NI are low, ranging from 0.6 to 1.1 at +0.25 h to +1 h after administration in
      GEP rats, but are more favourable at later times (1.6 at +2 h and 2.9 at +4 h).
      4. The substrate for nitric oxide synthase, L-arginine (500-5000 mg kg-1, i.p. or
      100-300 micrograms, i.c.v.) but not D-arginine (300 micrograms i.c.v.) is
      anticonvulsant in DBA/2 mice. L-Arginine (500-5000 mg kg-1, i.p. or 1800-6000
      micrograms, i.c.v.) is a more potent anticonvulsant than D-arginine (1500-2500 mg
      kg-1, i.p. or 6000 micrograms, i.c.v.) in GEP rats. 5. In DBA/2 mice, L-arginine
      (30 micrograms i.c.v.) reverses the anticonvulsant effect of 7-NI (50 mg kg-1,
      i.p.). 6. In GEP rats, low dose L-arginine (25-50 mg kg-1, i.p.) but not D
      arginine (50 mg kg-1, i.p.) reverses the anticonvulsant effect of low dose 7-NI
      (25 mg kg-1, i.p.). A higher dose of L-arginine (500 mg kg-1, i.p.) or 7-NI (50
      mg kg-1, i.p.) produces summation of anticonvulsant effect. 7. The product for
      nitric oxide synthase, L-citrulline (250-831 micrograms i.c.v.), is convulsant in
      DBA/2 mice. 8. The anticonvulsant effect of the neuronal selective nitric oxide
      synthase inhibitor, 7-nitroindazole, may therefore be mediated by L-arginine
      accumulation, as well as by a reduction in nitric oxide and L-citrulline
      formation in rodent models of reflex epilepsy.

PMID- 8872372
TI  - Isn't if offal?

PMID- 8872371
TI  - Similar decrease in spontaneous morphine abstinence by methadone and RB 101, an
      inhibitor of enkephalin catabolism.
AB  - 1. The dual inhibitor of enkephalin degrading enzymes, RB 101, is able to block
      endogenous enkephalin metabolism completely, leading to potent antinociceptive
      responses potentiated by blockade of CCKB receptors. In this study we have
      investigated the effects induced by RB 101 given alone, or with the CCKB
      antagonist, PD-134,308, on a model of spontaneous morphine withdrawal and
      substitutive maintenance in rats. 2. Animals were chronically treated with
      morphine for 7 days followed, 36 h after the interruption of drug administration,
      by a maintenance treatment for 5 days with methadone (2 mg kg-1, i.p.), clonidine
      (0.025 mg kg-1, i.p.), RB 101 (40 mg kg-1, i.p.), PD-134,308 (3 mg kg-1, i.p.) or
      a combination of RB 101 plus PD-134,308. Several behavioural observations were
      made during this period in order to evaluate the acute effects as well as the
      consequence of chronic maintenance induced on spontaneous withdrawal by the
      different treatments. 3. Methadone was the most effective compound in decreasing
      the spontaneous withdrawal syndrome after acute administration. Both, methadone
      and RB 101 had similar effectiveness in reducing opiate abstinence during the
      period of substitutive treatment. PD-134,308 did not show any effect when
      administered alone and did not modify the effect of RB 101. 4. Naloxone (1 mg kg
      1, s.c.) failed to precipitate any sign of withdrawal when injected at the end of
      the chronic maintenance treatment suggesting that, under the present conditions,
      methadone and RB 101 did not induce significant physical opiate-dependence. 5.
      The mildness of the side effects induced by chronic RB 101, suggests that
      systemically active inhibitors of enkephalin catabolism could represent a
      promising treatment in the maintenance of opiate addicts.

PMID- 8872373
TI  - In-vitro comparative study of a locally prepared corneal storage medium and
      Optisol.
AB  - OBJECTIVE: To compare the in-vitro safety and efficacy of two corneal storage
      media, Optisol and H-Sol, a chondroitin-sulfate-based medium containing
      hydrocortisone prepared at the Eye Bank of Canada (Ontario Division). DESIGN:
      Twenty paired corneas from human donors (mean age 67.9 years) were randomly
      assigned for storage in corneal viewing chambers at 4 degrees C in Optisol (10
      corneas) or H-Sol (10 corneas). The storage media were masked, and all
      measurements were done in a blinded fashion. OUTCOME MEASURES: Corneal clarity
      and thickness (measured at 0, 2, 4, 8 and 12 days), endothelial cell density and
      morphology (analysed at days 0 and 12). At day 12 cell viability was determined
      by staining with trypan blue and alizarin red S, and three randomly selected
      corneas from either medium were examined by scanning electron microscopy and
      transmission electron microscopy. RESULTS: Corneal thickness increased
      significantly from day 0 to day 12 in both Optisol and H-Sol, and corneal clarity
      decreased significantly in both media over this period (p < 0.05). At days 2, 4,
      8 and 12 the corneas stored in Optisol were significantly thinner than those
      stored in H-Sol (p < 0.05). There were no significant differences between the
      media in any of the other indices studied. Endothelial cell density decreased
      significantly in both Optisol and H-Sol (p < 0.05). There were no within-group
      differences in percentage of cell loss, coefficient of variation of cell area,
      figure coefficient or percentage of hexagonal cells. CONCLUSIONS: The difference
      in corneal thickness between Optisol and H-Sol may have been due to the higher
      concentration of chondroitin sulfate in the former (2.5%, compared with 2% in H
      Sol) or perhaps to the addition of other components to Optisol that are not
      present in H-Sol. Efforts continue to improve the formulation of H-Sol. Further
      studies are necessary to assess its safety and efficacy in vivo.

PMID- 8872374
TI  - Analysis of gene expression during experimental uveitis in the rabbit.
AB  - OBJECTIVE: To analyse the pattern of gene expression at the messenger RNA level
      during ocular inflammation in the rabbit. DESIGN: A gene screen assay was used to
      quantify specific binding over background (expression index) of various
      activation markers and cytokines in rabbit iris-ciliary body obtained during
      active experimental uveitis induced by injection of porcine lens protein (two
      animals) and in a control group (two animals). OUTCOME MEASURES: Expression
      indices corresponding to the activation markers and cytokines assayed. RESULTS:
      Compared with the control eyes, analysis of triplicate samples from the inflamed
      eyes showed a significantly higher expression index corresponding to the proto
      oncogenes c-fos, c-jun and Ha-ras, interleukin-2 and heat shock protein Hsp27 and
      a significantly lower index corresponding to transforming growth factor-beta (TGF
      beta) (p < 0.05). CONCLUSIONS: Active experimental lens-induced uveitis is
      associated with a significant rise in the gene expression of cellular activation
      factors and a decrease in an immunoprotective factor (TGF-beta) in the iris and
      ciliary body of the rabbit.

PMID- 8872375
TI  - Management of dislocated lens fragments after phacoemulsification surgery.
AB  - OBJECTIVE: To describe the management and visual outcome of patients with
      dislocated nuclear lens fragments. DESIGN: Case series. SETTING: Retina service
      at a university-affiliated hospital in Vancouver. PATIENTS: Fifty-four
      consecutive patients (28 men and 26 women) with retained lens fragments following
      phacoemulsification surgery referred for management from May 1990 to May 1994.
      The patients' ages ranged from 41 to 94 (average 74) years. RESULTS: Initial
      ocular findings in 52 patients included moderate or severe corneal edema in 23
      cases (44%), intraocular pressure greater than 25 mm Hg in 24 (46%), intraocular
      inflammation in 36 (69%), retinal detachment in 2 (4%) and vitreous hemorrhage in
      4 (8%). Of the eight patients managed conservatively with medical therapy six
      (75%) regained 20/40 or better vision. The remaining 46 patients underwent pars
      plana vitrectomy. The final visual acuity in this group was 20/40 or better in 30
      patients (65%), 20/50 to 20/100 in 8 (17%) and 20/200 or worse in 8 (17%).
      Patients who had an anterior chamber intraocular lens (IOL) implanted at cataract
      surgery had a significantly poorer visual outcome than those who received a
      posterior chamber IOL at vitrectomy (p = 0.03). CONCLUSIONS: When a significant
      segment of nucleus has dislocated during phacoemulsification surgery, vigorous
      irrigation or direct attempts to remove the lens fragments should be avoided.
      Anterior vitrectomy should be performed, and if adequate capsular support
      remains, a posterior chamber IOL should be inserted into the ciliary sulcus.

PMID- 8872377
TI  - Intranasal application of lidocaine jelly preoperatively in patients undergoing
      dacryocystorhinostomy.

PMID- 8872376
TI  - Scleral ectasia in rhegmatogenous retinal detachment.
AB  - OBJECTIVE: To determine the relation between retinal tears and scleral ectasia.
      DESIGN: Prospective study. SETTING: University-based referral practice in
      Montreal. PATIENTS: Fifty-seven consecutive patients with primary rhegmatogenous
      retinal detachments undergoing scleral buckling surgery. Patients with a history
      of trauma or previous cryotherapy, laser treatment or other vitreoretinal
      procedures were excluded. Fifteen patients with diabetes mellitus undergoing
      primary vitrectomy and prophylactic scleral buckling for nonclearing vitreous
      hemorrhage constituted the control group. OUTCOME MEASURES: Presence of scleral
      ectasia, visual acuity, refractive error. RESULTS: Thirty-one of the study
      patients were phakic and 26 were aphakic or pseudophakic. Fifteen (48.4%) of the
      phakic patients were found to have scleral ectasia, compared with six (23.1%) of
      the aphakic/pseudophakic patients and two (13.3%) of the control patients (p <
      0.05, chi 2 test). The most frequent location of ectasia was the superotemporal
      quadrant. Retinal tears occurred in the same quadrant as scleral ectasia in 12
      (80.0%) of the phakic patients. CONCLUSIONS: Scleral ectasia may be causally
      related to rhegmatogenous retinal detachment in certain cases.

PMID- 8872378
TI  - Excision of orbital cavernous hemangioma: refinement of strategy.

PMID- 8872379
TI  - Oncocytoma of the lacrimal sac associated with chronic dacryocystitis.

PMID- 8872380
TI  - Corneal ectasia secondary to excessive ocular massage following trabeculectomy
      with 5-fluorouracil.

PMID- 8872381
TI  - Central retinal vein occlusion associated with cavernous sinus thrombosis.

PMID- 8872382
TI  - Holmium laser sclerostomy.

PMID- 8872383
TI  - Gene structure prediction using information on homologous protein sequence.
AB  - In this paper a new approach for the prediction of protein coding gene structures
      is described. The principal scheme of prediction is as follows: first, the exons
      with the best potential are predicted in a sequence with unknown functions and a
      list of potential amino acid fragments coded by these exons is formed. Second,
      testing the homology between each amino acid fragment from the list and proteins
      from the SWISS-PROT database of amino acid sequences. One protein with the best
      homology is chosen out of all the homologous sequences. Third, reconstruction of
      the exon-intron structure, basing it on its homology with the chosen protein
      sequences. The method was tested on an independent control set (20 genes). The
      results were as follows: 21% of real exons were lost and 3% of non-real exons
      were found. This system can be used to refine the results of gene prediction
      systems, especially if highly homologous proteins are found in the amino acid
      sequence database.

PMID- 8872384
TI  - An annealing mutation operator in the genetic algorithms for RNA folding.
AB  - An annealing mutation operator in the genetic algorithms (GA) for RNA folding on
      a MasPar MP-2 has been designed. The mutation probability descends along a
      hyperbola with respect to the size of the secondary structure, hence the total
      number of mutations at each generation drops linearly. Especially for long
      sequences with thousands of nucleotides as opposed to hundreds of nucleotides,
      the new mutation operator can make the distribution of free energies over all
      processors on MasPar MP-2 converge only after hundreds of generations. Based upon
      this new mutation operator, a technique to terminate the GA is also developed.
      The new mutation operator runs very efficiently. Some variations of the annealing
      mutation operator are also discussed.

PMID- 8872385
TI  - qValue--a program to calculate comparative measures of genomic reorganisation
      from cytogenetic and/or linkage information.
AB  - A program qValue, which calculates a measure of the genomic reorganisation that
      has occurred between pairs of species since their divergence from a common
      ancestor, is described. The program takes a tab-delimited text file containing
      data describing the location of various genetic loci in multiple species and
      generates an output text file, also in tab-delimited format, that lists various
      parameters of genomic reorganisation between all possible pairs of species
      considered. This provides a useful tool for the developing field of comparative
      genome mapping, particularly in the study of the evolution of the vertebrate
      genome.

PMID- 8872386
TI  - TAXOKEY: a universal taxonomic key program using DOS text files and graphics.
AB  - A program (TAXOKEY.EXE), requiring only a few keystrokes to use, is described as
      a universal taxonomic key in the identification of plant and animal species by
      IBM-compatible personal computers. A DOS text file serves as the database for a
      key that can be dichotomous or with multiple choices. TAXOKEY can optionally
      display colour or monochrome screen pictures to illustrate the keys. Additional
      programs are described that are used to make the keys and check for errors, as
      well as convert .PCX graphic images for use with TAXOKEY. A second text file can
      be searched by TAXOKEY for information on particular species descriptions, notes
      and references.

PMID- 8872387
TI  - BioSCAN: a network sharable computational resource for searching biosequence
      databases.
AB  - We describe a network sharable, interactive computational tool for rapid and
      sensitive search and analysis of biomolecular sequence databases such as GenBank,
      GenPept, Protein Identification Resource, and SWISS-PROT. The resource is
      accessible via the World Wide Web using popular client software such as Mosaic
      and Netscape. The client software is freely available on a number of computing
      platforms including Macintosh, IBM-PC, and Unix workstations.

PMID- 8872388
TI  - CONRAD: a method for identification of variable and conserved regions within
      proteins by scale-space filtering.
AB  - Advanced sequencing techniques allow rapid deduction of individual amino acid
      sequences of highly related proteins. Due to their quasi-species nature, viral
      genomes (e.g. HIV-1) represent one of the most common sources of related
      proteins. Another example of related proteins are immunoglobulins. Local
      differences in amino acid conservation are useful indicators of potential domain
      structures and immunological or functional epitopes prior to structural analysis
      of proteins. Although variability indices can be calculated by several methods,
      delineation of boundaries between sequence stretches with similar variability
      indices is left to the user. We use algorithmic scale-space filtering for
      delineation of conserved and variable sequence stretches within a protein which
      is performed on an algorithmic basis avoiding arbitrary assignments. Out method
      correctly identified variable regions for the human immunoglobulin lambda-chain V
      regions (subgroup I). Prediction of the variable regions of the HIV-1 gp120 env
      protein was in agreement with empirical derived definitions. These examples
      indicate that our method is useful for the regional assignment of protein
      variability solely on the basis of amino acid sequences.

PMID- 8872389
TI  - Visualization of RNA secondary structures using highly parallel computers.
AB  - Results of RNA secondary structure prediction algorithm are usually given as a
      set of hydrogen bonds between bases. However, we cannot know the precise
      structure of an RNA molecule by only knowing which bases form hydrogen bonds. One
      way to understand the structure of an RNA molecule is to visualize it using a
      planar graph so that we can easily know the geometric relations among the
      substructures such as stacking regions and loops. To do this, we consider bases
      to be particles on a plane and introduce a repulsive force and an attractive
      force among these particles and determine their positions according to these
      forces. A naive algorithm requires O(N2) time but we can reduce it to O(NlogN)
      with an approximation algorithm which is often used in the area of N-body
      simulation. Our program is written in parallel object-oriented language
      'Schematic' which is recently developed. Efficiency of our implementation on a
      parallel computer and results of visualization of secondary structures are
      presented using cadang-cadang coconut viroid as an example.

PMID- 8872390
TI  - Detection of genes in Escherichia coli sequences determined by genome projects
      and prediction of protein production levels, based on multivariate diversity in
      codon usage.
AB  - We used principal component analysis to develop measures (called Z-parameters in
      this study) which reflect the diversity of codon usage in Escherichia coli genes.
      Protein production levels for 1500 CDSs (protein-coding sequences) identified by
      E.coli genome projects in Japan and the US were estimated from a correlation
      equation between Z1 and cellular protein content obtained through analysis of the
      genes experimentally characterized. Through the profile analysis of Z1 for E.coli
      sequences obtained by the Japanese Project, we predicted an additional 36 CDSs
      that had not been annotated in the International DNA Database. Thirty-one out of
      the 36 CDSs could be assigned to presumptive protein genes through a BLASTX
      search for recent protein databases in the Genome Net in Japan. Detailed
      examination of the Z1-parameter profile led us to assess sequencing errors which
      cause frame-shift.

PMID- 8872391
TI  - Image library of biological macromolecules.
AB  - An Image Library of Biological Macromolecules is described, which contains image
      and text files related to structures of biological macromolecules. Currently, the
      Library has approximately 3000 image files of approximately 300 structures of
      biological macromolecules whose coordinates are available in the Protein Data
      Bank and in the Nucleic Acid Database. The entries include all RNA structures,
      approximately 70 DNA structures, 150 proteins and a few carbohydrates. The
      Library contains further images of amino acids, of standard and modified
      nucleotides and of nucleic acid model structures. Each entry consists of an
      annotation file with bibliographic and sequence information and possibly
      comments, of a color-coded distance plot and of structure images. Almost all of
      the images are available both in a mono and in a stereo representation. Standard
      procedures for generating these images were strictly avoided. Therefore, mixed
      rendering, coloring and labeling techniques were used extensively. Since May 1995
      the Library has a growing division of images in the new Virtual Reality Modeling
      Language (VRML) format. The Image Library of Biological Macromolecules can be
      accessed via the World-Wide Web (http://www.imb-jena.de/IMAGE.html). There is a
      large number of structures determined by experimental and/or modeling techniques
      which are not intended to be included into the Protein Data Bank or Nucleic Acid
      Database for some reason. The Image Library could be a repository of these
      structures and of images of these and other structures of biological
      macromolecules including structures which are not known at atomic detail. Authors
      who are willing to make available images or coordinates to the scientific
      community via the Image Library of Biological Macromolecules are requested to
      contact the author.

PMID- 8872392
TI  - Development of an animal genome database and its search system.
AB  - An animal genome database has been developed on a Unix workstation and maintained
      by a relational database management system. This database has focused on the
      comparative gene mapping between species to assist the mapping of the genes
      related to phenotypic traits in livestock. The linkage maps, cytogenetic maps,
      polymerase chain reaction primers of pig, cattle, mouse and human, and their
      references have been included in the database, and the correspondence among
      species have been stipulated in the database. In order to search the database
      effectively, the World Wide Web server (http://ws4.niai.affrc.go.jp/) and the
      electronic mail server system (e-mail: jgbase-mail@ niai.affrc.go.jp) have been
      developed on different Unix workstations. These servers are connected to the
      Internet.

PMID- 8872393
TI  - The directory of P450-containing systems on WorldWide Web.
AB  - To facilitate access to electronic resources for all researchers working in the
      field of P450 proteins and P450-containing systems, a WorldWide Web server has
      been established called The Directory of P450-containing Systems at <
      http://www.icgeb.trieste.it/p450/ >. Currently it contains the most up-to-date
      list of sequences of both the P450 superfamily and proteins mediating electron
      transfer to P450, i.e. NADPH:P450 reductases, specific NAD(P)H:ferredoxin
      reductases, cytochrome b5 reductases, ferredoxins and cytochromes b5, and their
      homologues from different enzyme systems. All the referenced sequences are
      provided with accession numbers and cross-links to major sequence databanks: PIR,
      SWISS-PROT, EMBL/GenBank and PRF.

PMID- 8872394
TI  - IBIS version 3: an OSF/Motif-based interface for IBIS--integrated biological
      imaging system.
AB  - IBIS is a set of computer programs dedicated to the processing of electron
      micrographs, mainly for structural analysis of biological macromolecules. We
      present IBIS version 3, a UNIX/OSF/Motif 1.2-based package which carries out and
      provides visual display of the many operations essential to image analysis. To
      ensure portability, the software is written in FORTRAN 77 for computing
      mathematical functions and in C for display routines. A description of the IBIS
      OSF/Motif interface is given with the new functions added to the original
      version. IBIS v.3 is available free of charge to other laboratories on the
      internet via anonymous ftp (URL: ftp://ftp.univ-rennes1.fr/pub/
      incoming/IBIS.tar.Z).

PMID- 8872395
TI  - RNAdraw: an integrated program for RNA secondary structure calculation and
      analysis under 32-bit Microsoft Windows.
AB  - The use of algorithms for calculation and analysis of RNA secondary structures
      has largely been limited to mainframe computers, mainly due to the 16-bit memory
      restrictions imposed by MS-DOS. The program presented here, RNAdraw, moves
      calculations to the 32-bit Microsoft Windows environments with an intuitive user
      interface with extensive viewing, editing and printing possibilities. The
      algorithms for secondary structure/basepair probability matrix/heat curve
      calculation have been ported directly from a 32-bit Unix environment. RNAdraw
      also offers novel features such as the options to edit energy parameters, extract
      structures of different probability levels, create de novo secondary structures
      interactively, and combine viewing of structures and basepair probabilities.

PMID- 8872396
TI  - PM--protein music.

PMID- 8872397
TI  - Primer Master: a new program for the design and analysis of PCR primers.

PMID- 8872398
TI  - Three sets of Macintosh AppleScripts for the automatic submission of sequence
      data to the Internet BLAST server.

PMID- 8872399
TI  - The cognitive effects of ECT: bridging the gap between research and clinical
      practice.

PMID- 8872400
TI  - The road to practical (and pertinent) bedside memory testing.

PMID- 8872401
TI  - The "half-age" stimulation strategy for ECT dosing.
AB  - Energy levels affect the treatment efficacy and efficiency of electroconvulsive
      therapy (ECT). United States devices require preselection of energy dosage before
      stimulating patients, and two strategies have been proposed to determine an
      effective dosage, i.e., based on the patient's age and measured estimates of
      seizure threshold. The age method is criticized for overstimulation and an
      assumed association with increased cognitive effects. Threshold determination
      strategy is cumbersome and requires multiple stimulations, possibly placing
      patients at increased cardiovascular risk. In 35 patients, we examined an energy
      estimate for bilateral electrode placement at half the patient's age in "percent
      of energy" or joules delivered by the Thymatron and MECTA devices. Each patient
      required one stimulation in the first treatment to elicit motor seizures
      averaging 51.7 s. Subsequently, 20 patients were randomly assigned to either
      threshold titration followed by half-age for the first two treatments or the
      opposite (AB-BA design). Half-age energy was 7 J (30%) higher than titration
      estimates, corresponding to 55% energy of the age method. The relation of half
      age and titration estimates were confirmed in energy dosing records from two
      independent centers. Energy dosing by half-age calculation in bilateral ECT is
      simple, practical, avoids overdosing and repeat stimulation, and is a useful
      substitute for the more complex strategy based on threshold estimation.

PMID- 8872402
TI  - Relationship of seizure morphology to the convulsive threshold.
AB  - Twenty-two patients with major depression received a course of right unilateral
      ECT. The convulsive threshold (CT) was determined on the first treatment.
      Subsequent treatments were approximately 2.25 times CT. Seizure morphology for
      treatments 2-6 were rated for regularity (0-6 scale; low-high) and postictal
      suppression (0-3; low-high). Ratings of postictal suppression were log
      transformed to improve the approximation to a normal distribution. A preliminary
      analysis of variance with CT as the independent variable compared the seizure
      ratings at low, mid, and high CT. Second, linear regression models for the mean
      values of seizure regularity and postictal suppression were determined using age,
      gender, and the CT as predictor variables. The degree of postictal suppression
      varied inversely with age, male gender, and CT in this study. Our results
      suggested that CT made the greatest contribution to the model. Future studies
      examining the predictive value of seizure morphology parameters to clinical
      outcome should include measurement of CT.

PMID- 8872403
TI  - Completed suicide and recent electroconvulsive therapy in Finland.
AB  - In the research phase of the National Suicide Prevention Project in Finland, all
      completed suicides in Finland (N = 1,397) within a 12-month period were
      comprehensively examined by using the psychological autopsy method. In this
      study, we examined the number of cases having received electroconvulsive therapy
      (ECT) during the 3 final months before suicide. Only two such cases (0.14% of all
      suicides) were found, a figure remarkably low considering the high prevalence of
      severe depression in the suicide population. In both of the two cases, the
      quality of treatment was questionable, and suicide occurred during a depressive
      relapse. The findings indirectly support earlier reports suggesting ECT to have a
      preventive effect concerning suicide. However, alternative explanations, such as
      low base rate of use of ECT in Finland during the study period, or withholding
      ECT from some patients because of comorbidity, as well as a combined effect of
      all the three factors, need also to be considered. Among all suicides, those
      within 3 months after ECT are rare, and the possible efficacy of ECT in
      preventing suicide warrants further study.

PMID- 8872405
TI  - ECT after cerebral aneurysm repair.
AB  - Cerebral aneurysms or recent surgical repair of aneurysms are relative
      contraindications for electroconvulsive therapy (ECT), yet the literature
      contains at least three cases in which ECT resulted in no known CNS
      complications. The following case describes a course of ECT in a patient 4 months
      after he had undergone surgical repair of a posterior cerebral artery aneurysm.
      Blood pressure control in patients with CNS aneurysms and repaired aneurysms can
      be achieved through choice of anesthetic agent, and intravenous
      antihypertensives, thus reducing the risk of cerebrovascular complications.

PMID- 8872404
TI  - Exceptionally high seizure threshold: ECT device limitations.
AB  - Three patients had exceptionally high seizure threshold, as determined by an
      empirical titration procedure. Initial seizure threshold was 896 mC in two of the
      patients. The third patient had an initial threshold of 336 mC that increased to
      840 mC at the end of the course of electroconvulsive therapy (ECT), and remained
      elevated during a second course of ECT. All three patients were elderly men with
      complicated medical histories and ongoing low-dose benzodiazepine use. Each
      patient had an excellent response to ECT delivered with a custom modified device,
      capable of delivering more than twice the charge of ECT devices presently
      commercially available in the United States. Implications for the administration
      of ECT in patients with exceptionally high seizure threshold and the limitations
      of current device output are discussed.

PMID- 8872406
TI  - Experimental studies of the therapeutic action of electroconvulsive therapy in
      endogenous depression. The role of the electrical stimulation and of the seizure
      studied by variation of stimulus intensity and modification by lidocaine of
      seizure discharge.
AB  - Three methods of electroconvulsive therapy (ECT) were compared in respect of
      therapeutic effect in 69 attacks of endogenous depression in 65 patients, not
      previously treated by ECT during the actual period of illness. The treatments
      were given under barbiturate narcosis, with full muscular relaxation,
      administration of oxygen and electroencephalographic recording of the seizure
      discharge. In two methods grand mal seizures were evoked by supraliminal (A) and
      liminal stimulation (B), in the third (C) lidocaine (3 mg/kg i.v.) was given
      before the application of liminal stimulation. The seizure discharges in C were
      markedly shortened and their pattern modified, while between A and B the duration
      and pattern of the seizures were similar (Table 1). The patients were referred to
      the three treatments at random and the groups may be regarded as having a similar
      prognosis (Table 2-5, 7). The therapeutic outcome was estimated by rating several
      depressive symptoms according to a rating scale worked out for the purpose. The
      rating was performed before treatment, one week after the fourth treatment (a
      treatment pause was then made) and one week after the completed series. To obtain
      more reliable measures the scores for the various symptoms were added together to
      form a total score, which was then divided into a depression score and a
      retardation score, presumably measuring mainly depressive mood and psychomotor
      retardation. Differences in rating scores on two rating occasions were taken as
      measures of improvement. In addition, a global rating of improvement was made.
      The rating procedure was double blind. The principal results were: 1. After four
      treatments (three patients who recovered after three treatments included) the
      degree of improvement was in the rank order ABC with significant group
      differences for a few scores. After the completed series of treatments
      improvement in groups A and B did not differ significantly whereas in group C it
      was significantly smaller for some scores (Table 9). 2. The total number of
      treatments was significantly higher in group C than in group A and B, which did
      not differ significantly between themselves (Table 10). 3. A measure of
      therapeutic efficiency, improvement per treatment, was computed by dividing the
      degree of improvement as obtained from the differences in the combined scores and
      from the global score of improvement, by the number of treatments. After four
      treatments the improvement per treatment was highest in group A and lowest in
      group C, although in the comparisons AB and BC most differences did not reach
      significance. After the completed series the improvement per treatment did not
      differ significantly in groups A and B whereas in group C it was significantly
      less (Table 10). 4. In comparison with groups A and B, the total duration of
      seizure discharges was significantly shorter in group C both after four
      treatments and, in spite of the higher number of treatments, after the completed
      series. The improvement per second of seizure discharge was not significantly
      different in the groups although there was a tendency to a lower effect per
      second in group B (Table 11). It is concluded from these results that shortening
      of the seizure discharge decreases the therapeutic efficiency of ECT. Increase of
      the stimulus intensity, which apparently does not change the seizure discharge,
      possibly gives a more rapid therapeutic response but does not change the final
      degree of improvement or the number of treatments required to reach it. The
      depression-relieving effect of ECT is bound to seizure activity and not, or only
      slightly, to other effects of electrical stimulation.

PMID- 8872407
TI  - Different caffeine preparations.

PMID- 8872408
TI  - Etophylline as a proconvulsant.

PMID- 8872409
TI  - CT evaluation of the acute abdomen: bowel pathology spectrum of disease.
AB  - CT has become the primary imaging modality for the evaluation of the patient with
      clinical symptoms of an acute abdomen and a confusing clinical picture. Because
      these patients may have a range of various pathologies, CT has been used
      successfully to define the presence of disease and localize it to a specific
      organ or organ system. In this article, we review the various processes that
      resulted in acute abdomen focusing on the small bowel and colon. Specific
      entities discussed include appendicitis, diverticulitis, Crohn disease, and
      ulcerative colitis. Other less common processes, including pseudomembranous
      colitis, intussusception, and bowel ischemia are also discussed. The specific
      role of CT scanning and specific CT signs are discussed and addressed. The value
      of CT in relationship to other modalities and clinical evaluation is discussed
      and key statistics provided.

PMID- 8872410
TI  - Magnetic resonance imaging of thymic epithelial tumors.
AB  - The authors review their experience with magnetic resonance imaging (MRI) of the
      thymus and discuss the appearance of thymic epithelial tumors where MRI is
      clinically useful. Detailed descriptions of MRI findings in benign thymomas,
      invasive thymomas, and thymic carcinomas are provided. Most benign (noninvasive)
      thymomas appear with a slightly higher signal intensity than that of muscle on T1
      weighted images. On T2-weighted images, thymomas have an increase in signal
      intensity on both T1- and T2-weighted images. Neither fibrous septa nor lobulated
      internal architecture can be detected on MRI. Gd-DTPA-enhanced MR images show
      homogeneous enhancement. On the other hand, invasive thymomas show the same
      signal intensity as benign thymomas, both on T1- and T2-weighted images. However,
      invasive thymomas appear inhomogeneous in signal intensity on T2-weighted images.
      T2-weighted images also show a lobulated border, fibrous septa, and lobulated
      internal architecture, characteristic of most invasive thymomas. Irregularity of
      tumor margins indicating invasion into surrounding structures is noted in some
      cases of invasive thymomas. Exceptionally minute thymomas (< 1 cm in diameter)
      show a different signal intensity on MRI as compared to those of usual thymomas:
      both T1- and T2-weighted MR images show a low signal intensity mass with
      irregular or unclear borders. Histopathologically, these minute thymomas contain
      numerous tiny cysts and/or abundant collagenous tissues. Generally, thymic
      carcinomas, except carcinoid tumors, appear with a relatively low signal
      intensity on T1- and T2-weighted MR images in comparison to those of thymomas. In
      particular, well-differentiated squamous cell carcinomas appear with a low signal
      intensity on both T1- and T2-weighted images. Abundant collagenous tissue may be
      a causative factor for the low signal intensity on T2-weighted MR images. Thymic
      carcinomas appear slightly inhomogeneous on both T1- and T2-weighted images.
      Neither fibrous septa nor lobulated internal architecture can be detected in any
      thymic carcinoma. If MRI is performed on a patient with anterior mediastinal
      tumors, thymic carcinoma may be precisely diagnosed when characteristic MR
      findings are demonstrated.

PMID- 8872411
TI  - Positive inotropic therapy: an update and new agents.

PMID- 8872412
TI  - Neurochemical and pathological alterations following infusion of leupeptin, a
      protease inhibitor, into the rat brain.
AB  - It is known that proteases participate in cellular protein turnover and eliminate
      abnormal and potentially toxic proteins. Disturbed proteolysis may be responsible
      for generating the pathological features of some neurodegenerative disorders.
      Alzheimer disease, for instance, is the most common neurodegenerative disorder
      and a condition in which proteins of the cell membrane and cytoskeleton are
      abnormally processed and accumulated in the brain. It is of interest to
      investigate the effect of protease inhibitors on neurons and neurotransmitter
      systems in the brain. We examined neurochemical and morphological neuronal
      changes in the rat brain following long-term intracerebroventricular infusion of
      leupeptin, a potent calcium-activated protease (calpain) inhibitor. Leupeptin (5
      mg) was infused into the lateral ventricle using an osmotic minipump for 14 days.
      We found a significant reduction of regional choline acetyltransferase activities
      in the hippocampus, and of somatostatin concentrations in the hypothalamus and
      entorhinal cortex. Moreover, leupeptin caused a wide-spread, highly significant
      decrease in neuropeptide-Y concentrations. Leupeptin infusion produced severe
      degeneration of neuronal processes in both axons and dendrites, and accumulation
      of electron-dense bodies in the hippocampus. The results indicate that long-term
      intracerebroventricular infusion of leupeptin in the rat produces neurochemical
      and morphological changes resembling those of some neurodegenerative disease and
      aging. Abnormal proteolysis caused by either reduced protease or enhanced
      protease inhibitor activities might play an important role in these conditions.

PMID- 8872413
TI  - Cerebral metabolic changes in Alzheimer's disease: neurobehavioral patterns.
AB  - Regional cerebral glucose metabolism was surveyed in 37 Alzheimer's disease (AD)
      patients and 21 normal controls using positron emission tomography. Where
      possible, brain regions were specified according to their neurobehavioral
      function rather than as anatomically demarcated structures. Absolute metabolic
      values revealed significant differences (p < 0.05) between AD patients and
      controls for whole brain and the more superior supratentorial brain slices.
      Normalized values (region/brain stem) showed the most striking declines (p <
      0.001) in the association cortex (heteromodal region -21%; unimodal region -19%)
      and the primary sensory-motor cortex (-13%), with motor, auditory, and visual
      areas more affected than somatosensory areas. Limbic and paralimbic systems were
      equally affected (-14%; -11%; p < 0.001). Thalamus, striatum, cerebellum and
      brain stem were minimally or not affected. Neurobehaviorally defined
      hypometabolic regions largely parallel affected areas noted in anatomic and
      previous metabolic studies, with the possible exception of metabolic deficits in
      the primary sensory-motor complex. Conceivably, brain areas unaffected
      morphologically by the pathophysiological processes of AD may become
      dysfunctional due to a disruption of connectivity between regions.

PMID- 8872414
TI  - Letter and category fluency in Alzheimer's disease: a prognostic indicator of
      progression?
AB  - This study investigated differential patterns of performance by 40 Alzheimer's
      disease (AD) patients on standardised letter and category fluency tests. The
      performance of 24 age and education matched controls was used to classify
      patients as relatively more letter fluency impaired (L < C, n = 15) or more
      category fluency impaired (C < L, n = 25), and clinical features distinguishing
      these patient subgroups were investigated. Category performance was equally
      impaired in both patient subgroups, whereas the L < C subgroups were particularly
      impaired on letter fluency. The subgroups differed significantly in duration of
      illness (24 months for L < C group, 47 months for C < L group; t = 2.69, p =
      0.01) but did not differ in global dementia severity, age, education, general
      language ability, or functional status. Data on annual rate of change (ARC) on
      the Mini-Mental State Examination were available for 26 patients. While not
      statistically significant, subgroup ARC differences were suggestive of more rapid
      decline in the L < C patients, consistent with the finding of shorter duration of
      illness in this group. Word fluency tests may have potential as early predictors
      of rate of progression in AD.

PMID- 8872415
TI  - Apolipoprotein E and Alzheimer's disease: strength of association is related to
      age at onset.
AB  - Apolipoprotein E (apoE) epsilon 4 allele frequency among Alzheimer's disease (AD)
      patients is increased compared to control subjects and is influenced by the
      presence of other genetic factors and age at symptom onset. We examined the
      relationship between age at AD symptom onset and apoE by comparing the apoE
      epsilon 4 allele frequency of normal, elderly control subjects (n = 107) to that
      in AD patients (n = 123), divided into four age-at-onset periods. Additionally,
      the distribution of symptom onset ages of AD patients with and without apoE
      epsilon 4 alleles was determined. We observed increased apoE epsilon 4 allele
      frequencies between the AD onset ages of 55 and 75 years, but not at the extremes
      of onset ages (i.e. onset between 45 and 54 years of age and after age 75). Our
      data suggests that having an apoE epsilon 4 allele increases the likelihood that
      AD patients will develop symptoms in the middle range of onset ages. At the
      extremes of AD onset ages, non-apoE factors, including other genetic factors and
      age, are more important determinants of risk of developing AD.

PMID- 8872416
TI  - Serum amyloid P component level in Alzheimer's disease.
AB  - Serum amyloid P component (AP) is a normal plasma constituent that is observed in
      senile plaques and neurofibrillary tangles in brains of Alzheimer's disease (AD)
      patients. In this study we have evaluated the AP levels in sera of 16 patients
      with AD and in 16 control subjects by enzyme-linked immunosorbent assay. The AP
      level was 22.4 +/- (SD) 7.0 micrograms/ml in the AD group and 34.4 +/- (SD) 6.6
      micrograms/ml in the control group. The AP level in the AD group was
      significantly lower than that of the control group (p < 0.01). In the control
      group, there was no correlation between AP levels and age. Our results suggest
      that the production of AP by the liver (hepatocytes), thought to be the only
      source, may be suppressed in AD patients and that the deposition of AP in senile
      plaques and neurofibrillary tangles is not due to its overproduction.

PMID- 8872417
TI  - An enriched-population, double-blind, placebo-controlled, crossover study of
      tacrine and lecithin in Alzheimer's disease. The Tacrine 970-6 Study Group.
AB  - We studied the effects of 40 and 80 mg/day of tacrine on patients with probable
      Alzheimer's disease (AD) in an 8-week, randomized, double-blind, placebo
      controlled crossover trial with an enriched-population design. In the initial
      dose titration phase, an intent-to-treat analysis showed significantly more
      improvement with 80 mg/day of tacrine than placebo. In the subsequent crossover
      trial that included only 'responders', no significant improvement was observed
      with tacrine, whether or not it was given with lecithin. We found that
      individualized dose titration and enrichment strategies were not helpful and had
      the effect of reducing the power of the study. In the dose titration phase of
      this study we found that more impaired subjects were as likely to improve as
      those who were less impaired, suggesting that tacrine should be further
      investigated in more severely demented AD patients.

PMID- 8872418
TI  - Glial fibrillary acidic protein in the cerebrospinal fluid of patients with
      dementia.
AB  - Glial fibrillary acidic protein (GFAP) is the structural protein of the
      astroglial intermediate filament that forms the morphological basis of
      astrogliosis. In the present study, GFAP concentrations in cerebrospinal fluid
      were measured in patients with various dementia diseases. A significant
      correlation between GFAP and age was found both in the total dementia group and
      in the controls. Covariance analysis with GFAP as dependent variable and age and
      albumin ratio as covariates followed by multiple group comparisons showed that,
      with regard to GFAP levels, the controls (n = 39) differed significantly from the
      patients with vascular dementia (n = 20; p < 0.05), senile dementia of the
      Alzheimer type (n = 29; p < 0.05), and 'pure' Alzheimer's disease (n = 8; p <
      0.05), but not from those with frontal lobe dementia (n = 5).

PMID- 8872419
TI  - Apolipoprotein E in cerebrospinal fluid from patients with Alzheimer's disease
      and other forms of dementia is reduced but without any correlation to the apoE4
      isoform.
AB  - Apolipoprotein E (apoE) has been suggested to play a role in regenerative
      processes in the brain after trauma, and also in the pathogenesis of Alzheimer's
      disease (AD). We examined cerebrospinal fluid (CSF) apoE in a material consisting
      of 23 patients with early-onset AD (EAD), 31 with late-onset AD (LAD), 16 with
      frontal-lobe dementia (FLD), 25 with vascular dementia (VAD) and 25 controls. CSF
      apoE was decreased in all of EAD (1.8 +/- 1.1 mg/l; p < 0.0005), LAD (2.5 +/- 0.9
      mg/l; p < 0.0005), VAD (2.3 +/- 1.4 mg/l; P < 0.0005) and FLD (3.0 +/- 1.3 mg/l;
      p < 0.05) compared to the control group (5.7 +/- 4.0 mg/l). Since apoE4 has been
      found to bind to beta/A4-amyloid, and AD patients homozygous for apoE4 to have
      higher number of senile plaques than apoE3 homozygotes, we also examined the
      relation between CSF-apoE and apoE alleles. However, CSF-apoE did not
      significantly differ between patients with different apoE isoforms. Our findings
      support that apoE is involved in the pathogenesis of dementia disorders, both
      degenerative and vascular, but the CSF-apoE level is not influenced by the apoE
      isoforms. CSF-apoE may be used as an unspecific marker for neurodegenerative
      disorders, but not in purpose of differential diagnostics between different
      dementia disorders.

PMID- 8872420
TI  - Sleep-related breathing and movement disorders in healthy elderly and demented
      subjects.
AB  - Reported findings regarding sleep and sleep disorders in the elderly often
      conflict. Differences in results across studies may arise from selection of
      subjects, definitions and recording conditions. Our purpose was to test a method
      to study elderly, both healthy and demented, under the most natural conditions,
      without disturbing a fragile sleep. Using clinical parameters and a non
      disturbing recording method, we evaluated sleep quality in patients with
      carefully diagnosed dementia and compared the results to a group of healthy
      subjects between 50 and 70 years of age. Healthy subjects awoke less and had more
      quiet sleep than patients, while in patients a tendency for delayed sleep latency
      and more active sleep was observed. Consistent with previous investigations,
      sleep-related respiratory disorders (SRRD) were more common in patients than in
      the matched control group, and periodic breathing appeared only among patients.
      SRRD, of both obstructive and central types, were only mild, with periodic
      breathing dominating only among patients. Most of the desaturations were less
      than 10%. We did not observe respiration of the Cheyne-Stokes type. Patients had
      more sleep-related movement disorders (SRMD), particularly with increase of
      twitches and long movements. Periodic movements were not significantly increased
      among the patients. The method, and the data obtained may be useful for
      practitioners dealing with sleep disorders in geriatric populations. In the
      elderly, interactivity between sleep, SRRD and SRMD may be bidirectional and as
      elderly and demented subjects might have a distorted homeostatic sleep response,
      SRRD and SRMD, even in a mild form, may cause sleep disruption and worsen
      dementia.

PMID- 8872422
TI  - Environmental temperature modulates onset of independent feeding: warmer is
      sooner.
AB  - Individual dams and their litters were observed from Days 14-22 in a seminatural
      environment consisting of a nestbox attached to a larger, open field in which
      powdered chow was available. Ambient temperature in the field was either warm (30
      degrees C), moderate (21 degrees C), or cold (10 degrees C); nest temperature was
      always moderate. Behavior was monitored 12 hr/day by time-lapse video recording.
      The pups' egressions into the field and onset of independent feeding were
      temperature-related: Weaning was earliest in the warmth and increasingly late
      with decreasing ambient temperature. Among subjects in the cold condition, there
      was a positive correlation between duration in the field and duration feeding.
      Pup growth was unaffected by the temperature regimes. Environmental temperature
      has emerged as a determinant for early nest egressions and weaning onset.

PMID- 8872421
TI  - The enhancing effect of pyridostigmine on the GH response to GHRH undergoes an
      accelerated age-related reduction in Down syndrome.
AB  - Cholinergic agonists are known to potentiate GHRH-induced GH secretion, probably
      acting via inhibition of hypothalamic somatostatin release. Their effect is
      reduced in aging and in patients with Alzheimer's disease. This may be the
      consequence of age-related cholinergic impairment, which, in turn, could cause
      somatostatinergic hyperactivity leading to GH hyposecretion. As in Down syndrome
      (DS) neural alterations have been reported similar to those in aging, including
      cholinergic impairment, we verified the GH response to GHRH (1 microgram/kg i.v.
      at 0 min) alone or combined with pyridostigmine (PD), a cholinesterase inhibitor
      (60 and 120 mg, respectively, in children and adults, orally at -60 min) in 15 DS
      children (13.5 +/- 0.6 years) and in 11 DS young adults (24.0 +/- 1.2 years).
      Fifteen normal children (11.9 +/- 0.5 years), 15 normal adults (27.3 +/- 0.9
      years) and 16 normal elderly (76.3 +/- 1.5 years) were studied as controls. IGF-I
      levels showed an age-related reduction both in DS (children vs. adults, mean +/-
      SEM:354.8 +/- 44.9 vs. 204.4 +/- 29.4 micrograms/l, p < 0.02) and in controls
      (normal children vs. normal adults vs. normal elderly:281.4 +/- 36.3 vs. 175.4 +/
      11.2 vs. 72.5 +/- 6.6 micrograms/l, p < 0.001). The GH response to GHRH in DS
      children was higher than in DS adults (areas under curve: 1,197.6 +/- 241.5 vs.
      434.4 +/- 83.3 micrograms/l/h, p < 0.01). On the other hand, in normal subjects
      the GHRH-induced GH rise was similar in children and adults (1,056.2 +/- 128.4
      vs. 800.8 +/- 124.5 micrograms/l/h) and both were higher than that in elderly
      subjects (296.0 +/- 61.0 micrograms/l/h, p < 0.001). PD enhanced the GH response
      to GHRH both in DS and in normal subjects (p < 0.005). The GH response to PD+GHRH
      was lower in DS adults than in DS children (1,068.1 +/- 145.7 vs. 1,897.4 +/-
      198.8 micrograms/l/h, p < 0.001) as well as in normal elderly subjects with
      respect to that in normal children and normal adults (832.3 +/- 144.7 vs. 2,172.1
      +/- 156.1 and 2,347.6 +/- 322.4 micrograms/l/h, respectively, p < 0.001). The GH
      response to GHRH alone or combined with PD in DS adults was lower (p < 0.01) than
      that in normal adults and similar to that in normal elderly subjects. In
      conclusion, the present data demonstrate that the stimulated GH secretion in DS
      undergoes an accelerated age-related reduction. They also suggest the existence
      of a precocious impairment of central cholinergic activity in DS, which, in turn,
      could cause somatostatinergic hyperactivity and reduced GH secretion.

PMID- 8872423
TI  - The suppression of formalin-induced fos expression by different anesthetic agents
      in the infant rat.
AB  - Despite the importance of pediatric anesthesiology, the sites and mechanisms of
      anesthetic action in the neonate are not well described in either human or
      nonhuman species. This experiment investigated suppression produced by different
      anesthetic agents of neuronal activity in the lumbar spinal cord of the 3-day-old
      rat. The expression of the c-fos immediate early gene following formalin
      injection into the hindpaw was used as a marker for neuronal activity. Pups were
      anesthetized by one of the following often-used agents: methoxyflurane,
      acepromazine, a mixture of ketamine and xylazine, and hypothermia. All treatments
      induced behavioral anesthesia. Despite the behavioral anesthesia, the ketamine
      xylazine mixture was completely ineffective in suppressing formalin-induced-Fos
      expression. In contrast, methoxyflurane and hypothermia blocked the appearance of
      the Fos protein. Similarly, acepromazine was effective in eliminating some of the
      Fos-labeled nuclei. These data suggest that, in the infant rat, both hypothermia
      and methoxyflurane act in part at the spinal level by depressing either primary
      afferents or dorsal horn neuronal activity whereas the site of action for
      ketamine-xylazine may be located supraspinally.

PMID- 8872424
TI  - Development of ultrasonic vocalization responses in genetically heterogeneous
      National Institute of Health (N:NIH) rats. I. Influence of age, testing
      experience, and associated factors.
AB  - The N:NIH strain of rats was developed by the National Institutes of Health to
      provide a maximally heterogeneous population as a base for selective breeding
      (Hansen & Spuhler, 1984). Using the N:NIH strain, this laboratory will
      selectively breed adult animals that exhibited extremes of high or low ultrasonic
      vocalization (USV) rates as infants. Because nothing was known about USV in N:NIH
      rats, we characterized the development of isolation-induced USV in the first
      generation of this strain born in our laboratory. In a longitudinal/cross
      sectional study of pups tested at 3, 10, 15, and 18 days postnatally, N:NIH pups
      emitted their highest rates of USV at 3-4 days postnatally and calling remained
      high for 10 days before declining. USV rates were found to be a relatively
      environmentally stable behavioral trait in that repeated testing did not
      significantly affect the calling rates of either individuals or litters, and only
      at 3 days postnatal age did naturally occurring ambient temperature variations (6
      degrees C range) significantly affect USV responses. Individual differences in
      USV responses emerged by 10 days of age that were not simply correlations of body
      weight or rectal temperature, and pups at that age showed isolation calling rates
      that were highly predictive of their response levels 5 days later.

PMID- 8872425
TI  - Development of ultrasonic vocalization responses in genetically heterogeneous
      National Institute of Health (N:NIH) rats. II. Associations among variables and
      behaviors.
AB  - In this study, the first three generations of laboratory-reared, 10-day-old pups
      of the N:NIH strain were examined for ultrasonic vocalizations (USV) rates in
      response to 2 min of isolation. The purpose of the study was to determine
      baseline USV rates in these progenitor (PR1, PR2, PR3) generations prior to
      selective breeding for high and low rates of USV. In addition, this study aimed
      to detect sources of variation in USV between and within generations and sexes,
      and factors associated with USV during isolation across the generations. Data
      were collected from 532 10 day-old pups in 81 litters. Evaluation by principal
      component analyses revealed four factors corresponding roughly to constructs
      indicative of: thermoregulation; maturity and exploratory behavior;
      distress/anxiety, in which USV consistently appeared; and activity. Different
      component structures for each sex suggested that USV may represent different
      dimensions of anxiety for component structures for each sex suggested that USV
      may represent different dimensions of anxiety for the sexes, with some degree of
      overlap. Nonetheless, all variables measured during isolation testing accounted
      for only a small portion of the variance in individual pup USV (less than 9%) at
      10 days of age, when the effects of intercorrelations among all variables were
      taken into account. This suggests that variables currently measured do not
      represent a comprehensive model for the control of USV.

PMID- 8872426
TI  - Use of proximal and distal cues in place navigation by mice changes during
      ontogeny.
AB  - The ontogeny of the ability of C57BL/6 mice to use different cues for spatial
      learning was examined in several Morris water maze tasks. In the first two
      studies, three learning procedures were used, in which only distal cues (place
      learning), only proximal cues (cue learning), or both proximal and distal cues
      (cue + place learning) were pertinent to localize the platform. The results
      indicated that whatever the procedure, 22-day-old mice showed the same
      capabilities as adults. Moreover, in the cue + place-learning procedure, although
      the distal cues were not necessary to solve the task, both young and adult mice
      demonstrated the integration of distal information by exhibiting a strong spatial
      bias during a probe test. However, in the third experiment, it was shown that
      nonpertinent proximal cues perturbed 22-day-old mice in a place-learning
      procedure. Taken together, these results suggest that while even the youngest
      mice show striking spatial navigation abilities, young mice give greater
      importance to proximal cues for orientation whereas adults preferentially use
      distal information.

PMID- 8872427
TI  - They'll tell you who you are.

PMID- 8872428
TI  - Marginal vacuoles in fine-needle aspirates of follicular thyroid carcinoma.
AB  - Marginal vacuoles (MV) found in Giemsa-stained fine-needle aspirates of the
      thyroid gland have been observed in toxic and also in non-toxic goiters. The aim
      of our retrospective study was to disclose the incidence and diagnostic
      significance of MV in 46 smears from 43 patients with primary and/or metastatic
      follicular thyroid carcinoma (FTC). Typical MV, MV-like structures, or both were
      found in 14 of 36 specimens (39%) of the primary tumor and in four of seven
      specimens (57%) obtained from metastases of FTC. No association between the
      appearance of MV/MV-like structures and degree of tumor differentiation was
      demonstrated. On the other hand, MV or/and MV-like structures were more
      frequently (69%) documented in hyperthyroid patients (P < 0.05). Accordingly, our
      study demonstrated relatively frequent appearance of MV or MV-like structures in
      FTC independent of tumor differentiation. Their appearance, however, seems to be
      associated with hyperthyroidism.

PMID- 8872429
TI  - Chronic granulomatous disease of childhood: respiratory cytology.
AB  - Chronic granulomatous disease (CGD) of childhood is a rare inherited disease in
      which phagocytic cells fail to produce the normal respiratory burst in response
      to infectious stimuli, leaving the patient particularly susceptible to infections
      with bacteria and fungi that produce catalase. Between 1988 and 1993 at the NIH,
      58 pulmonary cytology specimens were obtained on 24 CGD patients. The number of
      specimens per patient ranged from one to 13 with an average 2.4. The 58 specimens
      included: 33 bronchoalveolar lavages; one bronchial brushing; 20 lung or pleural
      mass fine-needle aspirates; three pleural fluids, and one sputum. Two lung
      aspirates with insufficient material, five bronchoalveolar lavages performed post
      treatment to confirm clinical resolution of disease, and two bronchoalveolar
      lavages not submitted for culture were excluded from further analysis. Of the 49
      remaining specimens obtained from patients clinically suspected of having a
      pulmonary infection, cytology demonstrated a pathogenic organism in nine (18%).
      Microbiologic cultures were positive in 19/49 (39%). Cytology identified fungus
      in 8/13 (62%) of documented fungal infections, including four cases where
      microbiology was negative. Bacterial and mixed bacterial/fungal infections were
      usually not detected by cytology even with appropriate strains. No organisms were
      identified by cytology in the four cases of nocardia or the three cases of
      pseudomonas infection. The combination of cytology and microbiology provided the
      greatest diagnostic sensitivity, yielding a diagnosis in 22/49 cases (45%). Of
      the 27 cases with negative cytology and microbiology, an infectious agent was
      identified in eight upon submission of additional material: three cytology
      specimens and five tissue specimens. In the remaining 19 cases, no organisms were
      identified, however, the patients were treated presumptively. Characteristic
      pathologic features of granulomatous inflammation, necrosis, and giant cells were
      present in fine-needle aspirates, often when on organisms could be identified,
      but were not seen in other types of respiratory specimens.

PMID- 8872430
TI  - Cytology of metastatic adenocarcinoma of the prostate in pleural effusions.
AB  - Malignant pleural effusions due to prostatic carcinoma are rare. We examined the
      cytologic and clinical presentations of 14 malignant pleural effusions caused by
      prostate cancer. These cases represented 2.3% of all positive pleural effusions
      at our institution. All patients (n = 10) had high grade, high stage tumors,
      including three with small cell anaplastic carcinoma. Three cases had clinically
      documented metastases to pleura, and in two cases, metastases were documented at
      autopsy. Most tumor cells had large nucleoli and were arranged in small, loosely
      cohesive groups. Fluids due to the small cell type of prostate carcinoma often
      contained a mixture of cells similar to those seen in small cell carcinoma of
      other sites such as the lung, as well as cells resembling the more typical type
      of prostate cancer. Prostatic specific antigen and prostatic acid phosphatase
      were positive in less than 50% of these malignant effusions. We conclude that
      prostatic carcinoma in pleural effusions occurs most commonly in high grade, high
      stage tumors and has a characteristic cytologic appearance. Negative staining for
      PSA and PAP does not rule out a prostatic source for malignant cells in
      effusions.

PMID- 8872431
TI  - Cytologic features of necrotizing granulomatous inflammation consistent with cat
      scratch disease.
AB  - Approximately 2,000 cases of cat-scratch disease are reported annually. It is an
      uncommon cause of unilateral lymphadenopathy in children and adults. We present
      the cytologic features of necrotizing granulomatous lesions consistent with cat
      scratch disease from various sites. Eleven cases from 10 patients with a mean age
      of 16 yr (range, 2-33 yr) were biopsied by fine-needle aspiration. All gave a
      history of previous exposure to cats. Two children had atypical presentations;
      one with multiple hypodense areas within the liver and spleen, and the other with
      features of encephalitis. Other locations included lymph nodes from axilla,
      inguinal, preauricular, and cervical areas, and other body sites such as the
      scapula and the parotid gland. Histologic staging of the inflammatory process was
      correlated with cytologic features. There were 5 cases of early features, 3 cases
      in the middle phase, and 3 cases in late stage. The differential diagnosis of
      each stage is discussed. The 2 children with atypical presentations are described
      in detail.

PMID- 8872432
TI  - Nuclear grading and flow cytometric DNA pattern in fine-needle aspirates of
      primary breast cancer.
AB  - Fine-needle aspiration (FNA) biopsy is increasingly used in the diagnosis and
      biological characterization of breast carcinomas in patients who receive
      preoperative chemotherapy. In this context, nuclear cytologic grade supplemented
      by DNA content could play an important role in the morphologic assessment of
      breast cancer. In this study, DNA ploidy pattern, analyzed by flow cytometry on
      FNAs from 92 primary breast carcinomas, was related to cytologic nuclear grade.
      Twenty-seven samples were cytologic grade 1, 33 were grade 2, and 32 were grade
      3. Ploidy correlated with cytologic nuclear grade (P = 0.0001). Thirty percent of
      grade 1, 55% of grade 2, and 84% of grade 3 tumors were DNA aneuploid. For 30 of
      the 92 FNAs, it was possible to compare nuclear cytologic grade with the
      corresponding histologic grade using the Scarff, Bloom, and Richardson system. A
      high concordance (80%) between nuclear grade on FNAs and histologic grade was
      found. DNA flow cytometry in combination with nuclear cytologic grade might
      represent additional information for the characterization of breast cancer
      diagnosed by FNA.

PMID- 8872433
TI  - Detection of endocervical component by PAPNET system on negative cervical smears.
AB  - The presence of endocervical component (ECs) on cervical smears is considered
      essential for determining the adequacy of the Pap smear. The absence of an
      endocervical component in a negative smear suggests that a repeat Pap smear
      should be taken. We evaluated 635 manually screened negative cervical smears with
      a documented endocervical component. On PAPNET review, these cases were
      scrutinized for endocervical cells, metaplastic squamous cells (MSQ), or both.
      One-hundred and thirty-eight cases (22%), adequate manually, showed no ECs or
      MSQs by PAPNET. Twenty-three additional cases with both ECs and MSQ on manual,
      showed only MSQ by PAPNET, while another 30 cases (5%) with MSQ manually were
      totally missed by PAPNET. The results of this analysis shows that the
      endocervical component (ECs, MSQ) is missed by PAPNET in 27% of the cases.
      Without further improvement, this may pose the greatest deterrent for PAPNET as a
      primary screening instrument.

PMID- 8872434
TI  - Clear cell follicular adenoma of the thyroid: a case report.
AB  - A case of clear cell follicular adenoma of the thyroid is presented. The patient
      presented with a single, hyperactive nodule in the right lobe. The cytologic
      features include cellular smears with numerous disrupted cells and a granular
      background. The cytoplasm was abundant, pale grayblue vacuolated or granulated,
      but not clear. Thyreoglobulin was demonstrated both histologically and
      ultrastructurally, confirming the follicular-cell derivation of the tumor.
      Ultrastructurally, the cytoplasm was filled with empty, membrane bound vacuoles.
      The clear cell change might represent an artifact of formalin fixation and/or the
      paraffin embedding procedure.

PMID- 8872435
TI  - Cytology of hepatocellular carcinoma in serous fluids: a report of three cases.
AB  - Three cases of hepatocellular carcinoma (HCC) detected in serous fluids are
      reported. Two cases were detected in ascitic fluid and one case was identified in
      pleural fluid of a patient with widespread disease. The cytopathologic findings
      correlated well with the histologic type in each case. One case each of
      moderately differentiated, poorly differentiated, and fibrolamellar HCC were
      seen. In general, the fluids contained large polygonal cells, singly and in small
      clusters with large vesicular, occasionally multiple nuclei and prominent
      nucleoli. The current literature describing HCC in serous fluids is sparse. The
      identification of this tumor in serous fluids would allow diagnosis of new or
      recurrent disease and have implications for therapy.

PMID- 8872436
TI  - Exfoliative cytology of tracheobronchial adenoid cystic carcinoma.
AB  - The cytologic findings in the bronchial brushing and washing specimens of three
      cases of tracheobronchial adenoid cystic carcinoma are reported and compared with
      those reported in the literature. The cytodiagnostic features including
      cribriform epithelial clusters, epithelial balls, branching epithelial cylinders,
      cellular hyaline mucous globules, and a heretofore unemphasized diagnostic clue
      in exfoliative cytology--naked hyaline globules in washing smears, are
      illustrated and discussed.

PMID- 8872437
TI  - Collecting duct carcinoma of kidney: a cytological study and case report.
AB  - An intraoperative cytological imprint of a well study case of collecting duct
      carcinoma of the kidney is reported. Papillary structures, fibrotic desmoplastic
      stroma, tubular formations, and tumoral cells with high grade cytological atypia
      were found. Cytological details described help to avoid misinterpretation of
      collecting duct carcinoma as a metastatic tumor. The peculiar morphology, the
      immunohistochemical and biological behavior of this rare tumor justifies its
      classification in a special group.

PMID- 8872438
TI  - Metastatic neoplasms of the breast: fine-needle aspiration cytology of two cases.
AB  - Even when clinical data strongly suggest the presence of a metastatic neoplasm in
      the breast, this occurrence almost invariably raises great problems in diagnostic
      pathology. Both cases presented here had a well-recognized primitive neoplasm
      located elsewhere. Nonetheless, great importance was given to the application of
      ancillary techniques; the immunostains for "breast discriminants"--GCDFP15,
      HMFG1, and HMFG2--on tissue sections helped the recognition of a metastatic renal
      cell carcinoma; and the stains for S100 protein, smooth muscle actin,
      cytokeratins, and neurofilaments on cytologic material allowed the identification
      of a metastatic mediastinal leiomyosarcoma.

PMID- 8872439
TI  - Pseudomyxoma peritonei: a cytohistopathologic study of nine cases.
AB  - Cytologic examination of seven peritoneal fluids from nine patients with
      pseudomyxoma peritonei revealed papillary clusters and isolated neoplastic cells.
      In all patients, one or both ovaries were replaced by proliferating (borderline)
      mucinous epithelial tumors of grade I-II intestinal type while three patients had
      synchronous appendiceal tumors of similar morphologic appearance. Four of the
      nine patients demonstrated positive correlation between the presence of
      neoplastic cells in the ovarian interstitial mucin (pseudomyxoma ovarii), the
      extraovarian peritoneum, and the free peritoneal fluid. Two patients demonstrated
      a negative correlation. The submission of an inadequate amount of ovarian or
      appendiceal tissue for histologic examination may account for the discordance in
      three patients. It is concluded that pseudomyxoma peritonei is a distinct
      clinicopathologic entity which can be subdivided into two types, acellular and
      cellular. This distinction, unlike the specific cytomorphologic features, may
      have prognostic significance.

PMID- 8872440
TI  - Fine-needle aspiration of primary gallbladder carcinoma.
AB  - Primary carcinoma of the gallbladder is a rare neoplasm that is frequently
      difficult to diagnose preoperatively. The obstacles to diagnosis include vague
      symptoms and the relative inaccessibility of the gallbladder and cystic duct to
      biopsy. Cytological descriptions of gallbladder carcinoma are sparse and are
      largely confined to malignant cells identified in aspirated bile. Examination of
      bile is a fairly insensitive technique for diagnosing carcinoma, partially due to
      the degradative effect of biliary salts on cellular morphology. In the following,
      we report the findings of three cases of primary carcinoma of the gallbladder
      examined by fine-needle aspiration cytology.

PMID- 8872441
TI  - Pulmonary metastasis from a benign giant-cell tumor of the hand: report of a case
      diagnosed by fine-needle aspiration cytology.
AB  - We report on the fine-needle aspiration cytologic findings of a metastatic giant
      cell tumor of the right long digit to the lungs. The patient had undergone
      curettage of his giant-cell tumor of the finger twice 2 yr before his last
      admission. The lesion recurred 9 mo later, and a Ray resection of the right long
      digit was performed. Recently, a routine follow-up chest X-ray disclosed
      pulmonary metastasis. The aspirate from the lung yielded a highly cellular double
      cell population, composed of mononuclear stromal cells and an osteoclast-like
      giant-cell population. The rarity of this tumor and its metastatic potential can
      cause considerable difficulty in diagnosing this entity. Clinical data,
      radiologic findings, and cytologic features are important to reach the correct
      diagnosis. Fine-needle aspiration cytology is a reliable, relatively noninvasive,
      and cost-effective diagnostic tool in the diagnosis of visceral metastasis in
      giant-cell tumors.

PMID- 8872442
TI  - Similes and metaphors I: A nature walk through benign gynecologic cytology.
AB  - Similes and metaphors useful in benign gynecologic cytology are presented.
      Included are those pertaining to normal cellular elements, organisms,
      contaminants, and benign changes.

PMID- 8872443
TI  - Immunostaining of cell preparations: a comparative evaluation of common fixatives
      and protocols.
AB  - Immunostaining of cytologic preparations has been beset by problems of
      inconsistency, high background staining, and the requirement of different
      fixatives for different antigens. This study sought to identify a universal
      fixative and a simple fixation protocol suitable for a wide range of tissue
      antigens commonly employed for cytologic diagnosis. In an analysis of 23 fixation
      protocols involving acetone, acetone/methanol, acetone/formalin, glutaraldehyde,
      ethanol, methanol, and formal saline, fixation in 0.1% formal saline overnight at
      27 degrees C followed by 10 min fixation in 100% ethanol produced the most
      consistent and optimal preservation of immunoreactivity which could be further
      enhanced by pre-treatment with microwaves for epitope retrieval. Blocking of
      endogenous peroxidase was not necessary with this fixation protocol. Provided the
      smears were well air-dried (for at least 14 hr) prior to immersion in formal
      saline, there was no need to employ adhesive-coated glass slides. The smears
      could be kept at 27 degrees C (room temperature) for at least 7 days and at -70
      degrees C for 5 wk without loss of immunoreactivity as air-dried smears or after
      fixation in formal saline. One hundred percent acetone and 100% ethanol produced
      good morphology and immunoreactivity but a high level of background staining,
      whereas acetone-based mixtures resulted in inconsistent immunostaining.

PMID- 8872444
TI  - Are the globular eosinophilic paranuclear inclusions seen in fine-needle
      aspirates pathognomonic of malignant rhabdoid tumor?

PMID- 8872445
TI  - Cytokeratin positivity in seminoma.

PMID- 8872446
TI  - On the "irreducible false negative rate" in cervical cytology.

PMID- 8872447
TI  - Subclinical encephalopathy.
AB  - Subclinical hepatic encephalopathy (SHE)--cognitive deficits in the absence of
      overt encephalopathy--is frequently present in patients with cirrhosis. In the
      absence of biological correlates, diagnosis of SHE relies on psychometric tests.
      Attentional and motor abnormalities are the most common neurocognitive deficits.
      Sleep disturbances--a frequent complaint in cirrhosis--may be part of the
      spectrum of SHE. The impact of SHE on daily activities is controversial as
      patients may adapt their lives to cognitive limitations. Demanding activities,
      such as driving motor vehicles, may be impaired, though a blanket restriction
      appears premature. The benefit of treating SHE is not established.
      Antiencephalopathic drugs may be effective and can be considered in certain
      individuals.

PMID- 8872448
TI  - Transjugular intrahepatic portosystemic shunt and hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a frequent complication of portosystemic shunts
      with an incidence of about 25%. In side-to-side shunts, such as the transjugular
      intrahepatic portosystemic shunt (TIPS), there is relation between the incidence
      of postshunt HE and the diameter of the shunt. A smaller shunt with a diameter of
      < 8 mm has a lower risk of HE by maintaining some prograde portal perfusion in
      most patients and preventing arterioportal blood flow which may be of
      disadvantage in most conditions. On the other hand, a smaller shunt diameter
      limits the reduction in the portal-systemic pressure gradient and, therefore, may
      have a higher risk of rebleeding. The size of the shunt must be based on these
      risks which may be estimated by factors such as age, Child class, previous
      episodes of HE, size of varices and severity of previous bleedings. In
      retrospect, the decision for a specific diameter, i.e. pressure reduction, was
      right if the patient's liver function remained stable after TIPS, no HE occurred,
      and the varices disappeared. If this is not the case, the shunt diameter needs
      fine tuning with reduction in case of HE or functional deterioration, or
      enlargement if rebleeding occurred or the varices show a higher risk of such an
      event. This potential of fine tuning at any time is the major advantage of TIPS
      over the surgical shunting procedures.

PMID- 8872449
TI  - Pathogenesis of hepatic encephalopathy: potential future approaches.
AB  - Attempting to forecast future trends in research is difficult enough in any area
      but is well nigh impossible with the volatile field of hepatic encephalopathy
      (HE). Undaunted in this review it is suggested that more frequent use of intact
      animal models of HE to probe the pathogenesis of HE will occur with newly
      developed pharmacological agents. This process would be greatly facilitated by
      wide acceptance of a discrete number of reproducible animal models of this
      syndrome. Brief comments are made on the current status on some of the current
      hypotheses. Greater utilization of patients with subclinical HE for clinical
      studies will occur. Continuing interest in nuclear magnetic resonance imaging and
      spectroscopy findings peculiar to HE will be seen over the next decade.

PMID- 8872450
TI  - Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of
      clinical and subclinical hepatic encephalopathy?
AB  - Human hepatic encephalopathy (HE) is identified by a new noninvasive test, proton
      magnetic resonance spectroscopy (1H MRS) applied to the brain in a few minutes.
      Chemical changes identified by 1H MRS are elevated glutamine, decreased choline
      and decreased myoinositol. The specific association with HE is proven by clinical
      studies in patients with cirrhosis, overt and subclinical HE, by the appearance
      of the same changes after transjugular intrahepatic portasystemic shunt, and by
      their complete reversal by liver transplantation. The importance of the new
      marker, myoinositol, may lie in its role as an osmolyte regulating cell volume in
      the astrocytes. Other roles are also postulated. Progress in the management of
      both HE and subclinical hepatic encephalopathy may depend upon finding means,
      short of liver transplantation, which will restore cerebral choline and
      myoinositol. The finding of identical changes in experimental animals simplifies
      the search.

PMID- 8872451
TI  - Treatment of hepatic encephalopathy in patients with cirrhosis of the liver.
AB  - The treatment of hepatic encephalopathy is predominantly an empirical approach
      because the process pathogenesis of this syndrome is uncertain. Many treatment
      trials have been published, but few fulfill the usually accepted criteria for
      optimum study design. Lack of placebo controls, inadequate sample size and the
      difficulty in assessing the severity of encephalopathy are noteworthy examples.
      Treatments based on reducing ammoniagenic factors in the intestinal tract and
      promoting urinary waste nitrogen elimination are discussed. Other forms of
      therapy based on the false neurotransmitter and gamma-aminobutyric hypotheses are
      reviewed before outlining a practical approach to treatment of hepatic
      encephalopathy in clinical practice.

PMID- 8872452
TI  - Lactulose and combination therapy of hepatic encephalopathy: the role of the
      intestinal microflora.
AB  - Lactulose is the most frequently utilized agent in the treatment of hepatic
      encephalopathy because of its efficacy and the fact that it has few serious side
      effects. How this nonabsorbable disaccharide works has been a matter of
      controversy, but evidence suggests that metabolism by the enteric flora is
      necessary for its mechanism of action. When the intestinal flora metabolized
      lactulose, bacterial incorporation of nitrogen increases as does the bacterial
      mass. The presence of a carbohydrate and the acidic environment caused by the
      production of organic acids also act to reduce the breakdown of other nitrogen
      containing compounds to ammonia and other potential cerebral toxins. The
      administration of lactulose to humans causes an increase in fecal nitrogen, but
      very little increase in ammonia nitrogen. Most of the nitrogen is contained in
      the fecal bacterial and the soluble fractions of stool. The administration of
      lactulose causes a reduction in the urea production rate consistent with a
      reduced entry of ammonia into portal blood, but it does not appear to directly
      inhibit urea degradation. Other nonabsorbable saccharides, particularly those
      contained in dietary fiber, appear to have effects similar to those of lactulose.
      There is some evidence that neomycin can be given with lactulose to cause an
      additive effect in the treatment of hepatic encephalopathy. This effect is most
      prominent in patients who have not responded adequately to lactulose alone. At
      this point, the other antibiotics studied do not appear to have additive effects
      with lactulose.

PMID- 8872453
TI  - Synthesis of novel cyclic urea based HIV-1 protease inhibitors.
AB  - A series of novel HIV-1 protease inhibitors was prepared in a short
      stereospecific manner. These compounds have only one P1 substituent interacting
      with the S1/S1' binding site of HIV-1 protease and only one hydroxyl group
      interacting with the catalytic aspartic acid domain, X-ray crystallography
      confirmed the desired R, R configuration of the final products.

PMID- 8872454
TI  - Molecular simulation of 8-styrylxanthines.
AB  - Regarding theophylline as representative xanthine derivative, it was shown that
      the net charges of various semiempirical quantum chemistry methods are
      transferable by scaling. PM3 should be preferred for calculation of xanthine
      derivatives. Molecular modelling indicated that there is a conformational
      similarity of the lead structure of xanthine and adenosine derivatives. The
      substituents bound to the C8 of xanthine and to the C2 of adenosine derivatives
      are involved in the discrimination into adenosine A2 antagonists and agonists.
      The A2 affinity of xanthines is mainly determined by the type of N7 substitution
      (hydrogen/methyl), the lipophilic substituent constant related to the C8
      substituents, and the dipole moment of the molecules. To simulate chemically the
      A1 affinity, a further term (lowest unoccupied molecular orbital energy) must be
      added. In addition, hydrogen-bonding forces were hypothesized using a newly
      synthesized 3,6-diaminocarbazole derivative as synthetic adenosine
      pseudoreceptor.

PMID- 8872455
TI  - The synthesis and biological activities of oligodeoxynucleotides that are
      covalently linked to psoralen at their 5' ends.
AB  - Four oligodeoxynucleotides (15-mers), designated 13 through 16, and the
      corresponding conjugates, designated 17 through 20, in which psoralen was
      covalently linked to the 5' end of each oligonucleotide were synthesized.
      Compounds 16 and 20 contained a sequence that was complementary to part of the
      first four codons and the upstream sequence close to the ribosome-binding site of
      c-Ha-ras mRNA. Compounds 16 and 20 inhibited the growth of cells that had been
      transformed by the c-Ha-ras plasmid, with accompanying suppression of the
      expression of the activated c-Ha-ras oncogene. The antisense oligonucleotides 16
      and 20 also appeared to cause partial reversion of the major phenotypic
      characteristics of transformed cells, which included inhibition of anchorage
      independent growth. Compound 20, which contained psoralen, was a more efficient
      inhibitor of the growth of transformed cells than compound 16 without psoralen, a
      result that suggests psoralen might have increased the ability of the
      oligodeoxynucleotides to enter the cells.

PMID- 8872456
TI  - Hydrogen-bonding. Part 36. Determination of blood brain distribution using
      octanol-water partition coefficients.
AB  - It is shown that the octanol-water partition coefficient (Poct) cannot be used to
      predict blood brain distribution (BB) rectilinearly, but can be combined with
      Abraham solute descriptors to yield a predictive regression equation, eq (15), in
      which the solute descriptors sigma alpha H2 and sigma beta H2 are the overall
      summation hydrogen-bond acidity and basicity respectively. It is also
      demonstrated that of the various predictive models now available, that of
      Abraham, Chadha and Mitchell, eq (14), still yields the best results on a new
      test set of drug molecules; where the other solute descriptors are: R2, an excess
      molar refraction; pi H2, the dipolarity/polarisability; and Vx the characteristic
      volume of McGowan. Thus, solute dipolarity/polarizability, hydrogen-bond acidity
      and hydrogen-bond basicity favour blood, and solute size favours brain. logBB =
      +0.055 + 0.203logPoct - 0.507 sigma alpha H2 - 0.500 sigma beta H2 n = 49 rho =
      0.9491 sd = 0.201 F = 136.1 (15) logBB = -0.038 + 0.198R2 - 0.607 pi H2 - 0.715
      alpha H2 - 0.698 beta H2 + 0.995Vx n = 57 rho = 0.9522 sd = 0.197 F = 99.2 (14)

PMID- 8872457
TI  - Modelling the P2Y purinoceptor using rhodopsin as template.
AB  - The P2Y1 purinoceptor cloned from chick brain (Webb, T. et al (1993) FEBS Lett.,
      324, 219-225) is a 362 amino acid, 41 kDa protein. To locate residues tentatively
      involved in ligand recognition a molecular model of the P2Y purinoceptor has been
      constructed. The model was based on the primary sequence and structural homology
      with the G-protein coupled photoreceptor rhodopsin, in analogy to the method
      proposed by Ballesteros and Weinstein ((1995) Meth. Neurosci. 25, 366-428).
      Transmembrane helices were constructed from the amino acid sequence, minimized
      individually, and positioned in a helical bundle. The helical bundle was then
      minimized using the Amber forcefield in Discover (BIOSYM Technologies) to obtain
      the final model. Several residues that have been shown to be critical in ligand
      binding in other GPCRs are conserved in the P2Y1 purinoceptor. According to our
      model the side chains of these conserved residues are facing the internal cleft
      in which ligand binding likely occurs. The model also suggests four basic
      residues (H121 in TM3, H266 and K269 in TM6 and R299 in TM7) near the
      extracellular surface that might be involved in ligand binding. These basic
      residues might be essential in coordinating the triphosphate chain of the
      endogenous ligand adenosine 5'-triphosphate (ATP). Potential binding sites for
      agonists have been explored by docking several derivatives (including newly
      synthesized N6-derivatives) into the model. The N6-phenylethyl substituent is
      tolerated pharmacologically, and in our model this substituent occupies a region
      predominantly defined by aromatic residues such as F51 (TM1), Y100 (TM2) and F120
      (TM3). The dimethylated analogue of ATP, N6,N6-dimethyl-adenosine 5'
      triphosphate, is less well tolerated pharmacologically, and our model predicts
      that the attenuated activity is due to interference with hydrogen bonding
      capacity to Q296 (TM7).

PMID- 8872458
TI  - Structure-activity relationships defining the ACD-tricyclic cannabinoids:
      cannabinoid receptor binding and analgesic activity.
AB  - Previous studies of the structure-activity relationships (SAR) for binding of a
      series of AC-bicyclic cannabinoid structures to the cannabinoid receptors in rat
      brain (believed to comprise the CB1 subtype) demonstrated the importance of the A
      ring aryl C-3 side chain and phenolic hydroxyl substituents, and elucidated the
      importance of a C-ring hydroxyalkyl substituent [Melvin et al. Mol. Pharmacol.
      44, 1008-1015 (1993)]. The present investigation examines the SAR surrounding
      this region (D-ring) of the molecule that is not present in the structure of
      delta(9)-THC and other classical cannabinoid compounds. Both rigid fused ring
      benzo and cyclohexyl derivatives (creating the D-ring) retained binding affinity
      for the cannabinoid receptor. Extension of ketone or hydroxyl substituents from
      the C2 position of the D-ring resulted in a 3-fold increase in binding affinity
      over the unsubstituted structure. However, the fused ring structure is not
      critical for the interaction with the receptor in as much as opening the ring did
      not decrease the potency. Extension of the D-ring C-2 alcohol by one carbon in
      length resulted in a pair of structures, for which the greatest affinity for the
      CB1 receptor occurred for the hydroxymethyl group in the axial conformation [(+/
      )-CP-55,244]. Upon resolution, the latter provided a pair of enantiomers: (-)-CP
      55,244 was approximately 3-fold more potent than the racemic mixtures, and (+)-CP
      55,244 failed to bind to the CB1 receptor with an IC50 below 1 mM. Opening of the
      D-ring of these structures resulted in a loss of binding affinity. This study
      demonstrates that the potency could be optimized in (-)-CP-55,244 for both
      binding to the CB1 receptor and the biological activity of analgesia. In
      addition, the rigid positioning of the hydroxypropyl moiety of CP-55,940 enforced
      by the decalin ring structure of CP-55,244 increased the enantioselectivity by
      greater than 100-fold. These data define the critical stereochemistry for a
      region of the nonclassical ACD-tricyclic cannabinoid structure that contributes a
      potential hydrogen bonding component to the ligand-receptor interaction
      mechanism. Inasmuch as this region of the molecule is not present on classical
      ABC-tricyclic cannabinoid compounds, these studies elucidate a unique agonist
      recognition site on the CB1 receptor.

PMID- 8872459
TI  - Evolutionary conservation of sequence and expression of the bHLH protein Atonal
      suggests a conserved role in neurogenesis.
AB  - atonal is a Drosophila proneural gene that belongs to the family of basic helix
      loop-helix (bHLH)- containing proteins. It is expressed in the chordotonal organs
      and photoreceptor cells, and flies that lack Atonal protein are ataxic and blind.
      Here we report the cloning of atonal homologs from red flour beetle, puffer fish,
      chicken, mouse, and human. The bHLH domain is conserved throughout evolution,
      while the entire coding region is highly similar in mammals. Both the chicken and
      the mouse homologs are expressed early in embryogenesis in the hind brain, and
      specifically in cells predicted to give rise to the external granular layer of
      the cerebellum. In addition, these genes are expressed throughout the dorsal part
      of the spinal cord, in patterns different from those found for other genes, like
      LH-2 and wnt-1. The mouse homolog (Math1) maps to mouse chromosome 6, and the
      human homolog (HATH1) to human chromosome 4q22. Two neurological mouse mutants,
      Lc and chp, were found to map to the vicinity of Math1, but are not caused by
      mutations in Math1. The evolutionary conservation of this gene and its mRNA
      expression patterns during embryogenesis suggests that it plays a key role in the
      development of the vertebrate central nervous system.

PMID- 8872460
TI  - New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the
      slow-channel congenital myasthenic syndrome.
AB  - Mutations in genes encoding the epsilon, delta, beta and alpha subunits of the
      end plate acetylcholine (ACh) receptor (AChR) are described and functionally
      characterized in three slow-channel congenital myasthenic syndrome patients. All
      three had prolonged end plate currents and AChR channel opening episodes and an
      end plate myopathy with loss of AChR from degenerating junctional folds. Genetic
      analysis revealed heterozygous mutations: epsilon L269F and delta Q267E in
      Patient 1, beta V266M in Patient 2, and alpha N217K in Patient 3 that were not
      detected in 100 normal controls. Patients 1 and 2 have no similarly affected
      relatives; in Patient 3, the mutation cosegregates with the disease in three
      generations. epsilon L269F, delta Q267E and beta V266M occur in the second and
      alpha N217K in the first transmembrane domain of AChR subunits; all have been
      postulated to contribute to the lining of the upper half of the channel lumen and
      all but delta Q267E are positioned toward the channel lumen, and introduce an
      enlarged side chain. Expression studies in HEK cells indicate that all of the
      mutations express normal amounts of AChR. epsilon L269F, beta V266M, and alpha
      N217K slow the rate of channel closure in the presence of ACh and increase
      apparent affinity for ACh; epsilon L269F and alpha N217K enhance desensitization,
      and epsilon L269F and beta V266M cause pathologic channel openings in the absence
      of ACh, rendering the channel leaky, delta Q267E has none of these effects and is
      therefore a rare polymorphism or a benign mutation. The end plate myopathy stems
      from cationic overloading of the postsynaptic region. The safety margin of
      neuromuscular transmission is compromised by AChR loss from the junctional folds
      and by a depolarization block owing to temporal summation of prolonged end plate
      potentials at physiologic rates of stimulation.

PMID- 8872461
TI  - Identification of a hot spot for microdeletions in patients with X-linked
      deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4.
AB  - Small mutations in the POU domain gene POU3F4 were recently shown to cause X
      linked deafness type 3 (DFN3) in nine unrelated males. The POU3F4 gene was found
      to be located outside four of five deletions associated with DFN3. Two of these
      deletions were situated more than 400 kb proximal to POU3F4. Employing PCR
      analysis of sequence tagged sites from this region we initially identified novel
      deletions in two DFN3 patients. To investigate this chromosomal segment in more
      detail, we extended a previously established 850 kb cosmid contig in the
      centromeric direction to a total size of 1500 kb. Cosmids from this contig were
      hybridized to DNA of 11 unrelated males with DFN3. In two patients, we identified
      deletions encompassing the POU3F4 gene and variably sized segments of Xq21.1. In
      six of the nine remaining patients which lacked mutations in the POU3F4 gene,
      smaller deletions were identified which, with one exception, overlap in a 8 kb
      segment 900 kb proximal to the POU3F4 gene. In one patient, we identified several
      small deletions in the vicinity of the 8 kb DNA segment. Together, deletions
      account for 56% (13/23) of all known DFN3 mutations, most (10/13) of which do not
      encompass the POU3F4 gene. The combined molecular data suggest that the deletion
      hot spot region in Xq21.1 contains another DFN3 gene or, alternatively, a
      sequence element involved in transcriptional regulation of POU3F4.

PMID- 8872462
TI  - In vitro expression analysis shows that the secretory form of gelsolin is the
      sole source of amyloid in gelsolin-related amyloidosis.
AB  - Amyloidoses are a group of diseases where abnormal fibrillar protein deposits
      accumulate in patients' tissues. In familial amyloidosis of the Finnish type
      (FAF), or gelsolin-related amyloidosis, the amyloid subunit protein consists of
      gelsolin peptides of amino acids 173-243 with the disease causing substitution at
      Asp187. Gelsolin is an actin-modulating protein and exists in both secretory and
      intracellular forms both encoded by a single gene in chromosome 9. We have
      previously shown that the FAF-associated forms of secretory gelsolin carrying the
      Asp187Asn or Asp187Tyr mutations are abnormally processed in cells, resulting in
      the secretion of an aberrant 68 kDa carboxyterminal fragment. Here we demonstrate
      by N-terminal sequencing that the amino terminus of this abnormal fragment is the
      amino acid 173 and thus represents the N-terminus of the FAF amyloid. We also
      provide evidence that the same truncated gelsolin can be found among the aberrant
      gelsolin fragments detected in patients' CSF. Finally, we also expressed the FAF
      associated forms of intracellular gelsolin in COS-1 cells, and found no
      abnormality in their processing opposite to secretory form. Our results provide
      strong evidence that the secretory gelsolin is solely responsible for the amyloid
      formation in FAF.

PMID- 8872463
TI  - Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients
      with sporadic, familial and hereditary colorectal cancer.
AB  - To date, at least four genes involved in DNA mismatch repair, hMSH2, hMLH1, hPMS1
      and hPMS2, have been demonstrated to be altered in the germline of patients with
      hereditary nonpolyposis colorectal cancer (HNPCC). Additionally, defective
      mismatch repair is thought to account for the observation of microsatellite
      instability (MIN) in tumors from these patients. The genetic defect responsible
      for the MIN+ phenotype in sporadic colorectal cancer, however, has yet to be
      clearly delineated. In order to better understand the role of somatic and
      germline alterations within hMSH2 and hMLH1 in the process of colorectal
      tumorigenesis, we examined the entire coding regions of both of these genes in
      seven patients with MIN+ sporadic colorectal cancer, 19 patients with familial
      colorectal cancer, and 20 patients meeting the strict Amsterdam criteria for
      HNPCC. Thirteen germline, two somatic, and four neutral alterations were
      identified. The two somatic mutations occurred in patients having familial
      cancer, while the germline mutations were distributed among one sporadic (14%),
      three familial (16%), and nine HNPCC (45%) cases. All patients with identified
      mutations in the mismatch repair genes, whose tumors were available for analysis,
      demonstrated MIN. On the other hand, we could not identify mutations in the
      subset of clinically defined HNPCC patients with MIN negative tumors nor in the
      majority (6/7) of MIN+ sporadic tumors.

PMID- 8872464
TI  - Founder effect in spinal and bulbar muscular atrophy (SBMA).
AB  - We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor
      gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X
      chromosomes and 173 control X chromosomes in Japanese males. The control
      chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32
      repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/-
      3 copies. The control chromosomes had seven different alleles of the (GGC)n
      repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%),
      while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles
      were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%).
      (GGC)n size distribution was significantly different between SBMA and control
      chromosomes (P < 0.0001), indicating the presence of linkage disequilibrium.
      There was no allelic association between the (CAG)n and (GGC)n microsatellites
      among control subjects as well as SBMA patients, which suggests that a founder
      effect makes a more significant contribution to generation of Japanese SBMA
      chromosomes than new mutations.

PMID- 8872465
TI  - Cloning and expression analyses of mouse dystroglycan gene: specific expression
      in maternal decidua at the peri-implantation stage.
AB  - While constructing a catalog of mouse cDNAs which are expressed in the maternal
      fetal interface during the peri-implantation period, we encountered a 1.6 kb cDNA
      clone showing a strong sequence similarity to the 3' untranslated region of the
      human dystroglycan gene. We cloned an additional 1.7 kb cDNA by reverse
      transcriptase-PCR (RT-PCR) and confirmed that this is a true mouse homolog of
      human dystroglycan cDNA by sequence analyses, Southern blotting, and genetic
      mapping of this gene on the distal region of mouse chromosome 9. Although it is
      well established that dystroglycan, a transmembrane protein, plays an important
      role in muscle tissues by bridging intracellular dystrophin to the laminin in the
      extracellular matrix, its role in non-muscle tissues remains elusive. To further
      investigate the role of the dystroglycan gene at the peri-implantation stage, we
      analyzed the expression patterns of this gene by in situ hybridization, which
      revealed that this gene is specifically expressed in decidual cells, especially
      in the cells surrounding the implantation site at 6.5, 7.5, and 8.5 day post
      conception (p.c.) stages, but not expressed in non-pregnant endometrial cells of
      uterus nor in the decidua at 12.5 day p.c. Further analyses by RT-PCR confirmed
      that the amount of dystroglycan mRNA in 8.5 day p.c. decidua was indeed 100-fold
      higher than that of non-pregnant uterus and 12.5 day p.c. mature placenta. These
      results suggest that dystroglycan may work as a mediator for adhesion between
      decidual cells themselves or between decidual cells and trophoblast cells, and
      provide a structural and functional support for maintaining pregnancy at its
      early stage.

PMID- 8872466
TI  - A 27 base-pair deletion of the anti-mullerian type II receptor gene is the most
      common cause of the persistent mullerian duct syndrome.
AB  - The persistent mullerian duct syndrome, characterized by the lack of regression
      of mullerian derivatives, uterus and tubes in otherwise normally masculinized
      males, is a genetically transmitted disorder implicating either anti-mullerian
      hormone (AMH), a member of the transforming growth factor-beta superfamily, or
      its type II receptor, a serine/threonine kinase homologous to the receptors of
      other members of the transforming growth factor-beta superfamily. We have now
      performed molecular studies in a total of 38 families. The basis of the
      condition, namely 16 AMH and 16 AMH receptor mutations, was identified in 32
      families. The type of genetic defect could be predicted from the level of serum
      AMH which is very low or undetectable in patients with AMH mutations and at the
      upper limit of normal in receptor mutations. Whereas AMH mutations are extremely
      diverse, patients from 10 out of 16 families with receptor mutations had a 27 bp
      deletion in exon 10 on at least one allele. This deletion is thus implicated in
      approximately 25% of patients with persistent mullerian duct syndrome. All AMH
      and AMH receptor mutations were consistent with an autosomal recessive mode of
      transmission.

PMID- 8872467
TI  - Breakpoint diversity illustrates distinct mechanisms for Robertsonian
      translocation formation.
AB  - Robertsonian translocations are the most common chromosomal rearrangements in
      humans. The vast majority of the ten possible nonhomologous types of Robertsonian
      translocations ascertained are rob(13q14q) and rob(14q21q). Recombination between
      homologous sequences on nonhomologous chromosomes has been proposed as a
      mechanism leading to the preferential formation of rob(13q14q) and rob(14q21q).
      However, little evidence exists to indicate whether the remaining less common
      Robertsonian translocations form through a similar mechanism. To better elucidate
      the mechanisms involved in Robertsonian translocation formation, we have used
      fluorescence in situ hybridization to localize the breakpoints in 56
      nonhomologous Robertsonian translocations. This study revealed highly variable
      locations of breakpoints in seven types of the less common Robertsonians, while
      nearly all rob(13q14q) and rob(14q21q) analyzed displayed breakpoints in the same
      locations. Therefore, this study provides direct evidence that rob(13q14q) and
      rob(14q21q) form through a specific mechanism, possibly involving homologous
      recombination, which is distinct from the mechanism(s) that contributes to the
      formation of the remaining types of Robertsonian translocations.

PMID- 8872468
TI  - Human, canine and murine BRCA1 genes: sequence comparison among species.
AB  - Five to ten percent of breast cancer in the western world may be attributed to
      the inheritance of highly penetrant mutations in the breast and ovarian cancer
      susceptibility gene, BRCA1. The biological function of BRCA1 and factors
      affecting expressivity, such as gene-environment and gene-gene interactions, may
      be more effectively studied in appropriate animal models. We report the cloning
      and sequencing of the canine and murine BRCA1 genes and contrast the sequences
      with human BRCA1. The amino terminal 120 residues of the gene are > 80% identical
      among the three species. The C-terminus is also highly conserved, containing an
      80 amino acid stretch that is over 80% identical. Motifs of likely functional
      significance are maintained, including the amino terminal RING finger motif
      (amino acids 24-64) and the granin consensus sequence (1214-1223). The
      distribution of missense mutations and neutral polymorphisms identified in BRCA1
      linked breast cancer suggests that disease associated missense mutations occur at
      highly conserved residues whereas polymorphisms are in regions of lower
      conservation. Among eighteen missense mutations with unknown consequences, seven
      occur in amino acids that are identical across species. Four of these seven
      (E1219D, A1708E, P1749R and M1775R) are also within conserved domains. Taken
      together, these data predict regions of the gene which may be critical for normal
      function.

PMID- 8872469
TI  - Reduced levels of dystrophin associated proteins in the brains of mice deficient
      for Dp71.
AB  - Duchenne muscular dystrophy (DMD) is a progressive degenerative lethal muscle
      disease. A significant proportion of DMD affected children suffer also from
      mental retardation. The rod shaped protein, dystrophin, which is absent from or
      defective in the muscle of DMD patients, binds to a number of membrane associated
      proteins (known collectively as dystrophin associated proteins [DAPs]). The
      levels of DAPs is greatly reduced in the muscle of DMD patients and mdx mice,
      which lack dystrophin. In addition to dystrophin isoforms, the DMD gene codes
      also for several smaller proteins. One of the small proteins, Dp71, is expressed
      in most or all non-muscle tissues and is the major DMD gene product in the brain.
      The function of the small DMD gene products is unknown. Here we show that mutant
      mice which do not express the smaller non-muscle products of the DMD gene have a
      reduced level of DAPs in their brain. This suggests that Dp71 is important for
      the formation and/or stabilization of a DAPs complex in brain.

PMID- 8872470
TI  - A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal
      regions affected in Down syndrome and maps to the critical region.
AB  - The minibrain (mnb) gene of Drosophila melanogaster encodes a serine-threonine
      protein kinase with an essential role in postembryonic neurogenesis. A
      corresponding human gene with similar function to mnb could provide important
      insights into both normal brain development and the abnormal brain development
      and mental retardation observed in many congenital disorders. Trisomy 21 or Down
      syndrome (DS) is the most frequent human birth defect. It is associated with
      mental retardation and a broad spectrum of physical abnormalities. A region on
      human chromosome 21 has been designated the Down syndrome critical region (DSCR)
      and when present in three copies, this is responsible for many of the
      characteristic features of DS, including mental retardation. We have isolated a
      human homologue of mnb from the DSCR. MNB encodes a 6.1 kb transcript which is
      expressed in foetal brain, lung, kidney and liver. Using a human probe, two major
      transcripts (6.1 and 3.1 kb) were identified in mouse and expression was detected
      in situ in several regions of the mouse brain, including the olfactory bulb, the
      cerebellum, the cerebral cortex, the pyramidal cell layer of the hippocampus and
      several hypothalamic nuclei. This expression pattern corresponds to the regions
      of the brain that are abnormal in individuals with DS and suggests that
      overexpression of MNB could have detrimental consequences in DS patients.

PMID- 8872471
TI  - Spinocerebellar ataxia type-1 and spinobulbar muscular atrophy gene products
      interact with glyceraldehyde-3-phosphate dehydrogenase.
AB  - Spinocerebellar ataxia type1 (SCA1) is one of several neurodegenerative disorders
      caused by expansions of translated CAG trinucleotide repeats which code for
      polyglutamine in the respective proteins. Most hypotheses about the molecular
      defect in these disorders suggest a gain of function, which may involve
      interactions with other proteins via the expanded polyglutamine tract. In this
      study we used ataxin-1, the SCA1 gene product, as a bait in the yeast two-hybrid
      system and identified the glycolytic enzyme glyceraldehyde-3-phosphate
      dehydrogenase as an ataxin-1 interacting protein. In addition, the yeast two
      hybrid data demonstrate that wild type and mutant ataxin-1 form homo and
      heterodimers. Physical interaction between GAPDH and ataxin-1 was also
      demonstrated in vitro. To investigate if GAPDH might interact with other
      glutamine repeat-containing proteins involved in neurodegenerative disorders, we
      tested its binding to the androgen receptor which is mutated in spinobulbar
      muscular atrophy. The androgen receptor interacts with GAPDH both in the yeast
      two-hybrid system and in vitro. The binding of both ataxin-1 and the androgen
      receptor to GAPDH does not vary with the length of the polyglutamine tract. While
      provocative, these findings do not address the selective neuronal loss in each of
      these disorders in light of the wide expression patterns of GAPDH and the
      respective polyglutamine containing proteins. Nonetheless, such interactions may
      increase the susceptibility of specific neurons to a variety of insults and
      initiate degeneration.

PMID- 8872472
TI  - KVLQT1 mutations in three families with familial or sporadic long QT syndrome.
AB  - Congenital long QT syndrome (LQTS) is a heterogeneous group of heritable
      disorders characterized by prolongation of the QT interval on the
      electrocardiogram, ventricular arrhythmias and sudden death. At least four genes
      can, when mutated, produce this phenotype. Of these genes, the recently
      identified KVLQT1 potassium channel is thought to be the one most commonly
      responsible. In this study, we used single strand conformational polymorphism
      (SSCP) analysis to screen two large and nine small LQTS families for mutations of
      the KVLQT1 potassium channel gene. We identified a novel missense mutation in two
      unrelated families which substitutes a serine for a conserved glycine in the
      putative pore region of the KVLQT1 channel. In a third family, a new alanine to
      valine mutation at a CpG dinucleotide resulted in the spontaneous occurrence of
      the long QT syndrome in monozygotic twin offspring of unaffected parents.
      Mutations at this same nucleotide have been observed in eight of the 19 LQTS
      families determined to have KVLQT1 mutations, suggesting this is a mutational hot
      spot. Both of these mutations alter the amino acid sequence in, or adjacent to,
      the pore of the channel and many diminish the channel's ability to conduct a
      repolarizing potassium current. To date, all KVLQT1 mutations determined to cause
      the LQTS are missense mutations. These data confirm the role of KVLQT1 in the
      LQTS and suggest that mutant KVLQT1 proteins may exert a dominant negative effect
      on repolarizing potassium currents by forming multimers with normal potassium
      channel protein subunits, dramatically reducing the number of fully-functional
      KVLQT1 channels.

PMID- 8872473
TI  - Genetic variation at a splicing branch point in intron 9 of the low density
      lipoprotein (LDL)-receptor gene: a rare mutation that disrupts mRNA splicing in a
      patient with familial hypercholesterolaemia and a common polymorphism.
AB  - Mutations in the coding sequence, splice junctions or promoter of the gene for
      the low density lipoprotein (LDL) receptor are known to be the underlying cause
      of familial hypercholesterolaemia (FH), but mutations of this type cannot be
      identified in all patients with a clinical diagnosis of FH. We show here that
      minor sequence changes elsewhere in introns can be deleterious. A minor
      rearrangement 30 bp upstream from the junction of intron 9 with exon 10 was
      detected as a heteroduplex in amplified genomic DNA from one out of 300
      heterozygous FH patients. The mutation destroys the only consensus sequence for a
      splicing branch point in intron 9 and analysis of mRNA from cells from the
      patient showed that it causes retention of intron 9 or, more rarely, in the use
      of cryptic splice sites in exon 10. The effect of the mutation on mRNA splicing
      was confirmed by analysis of mRNA in cells transfected with LDL-receptor mini
      gene constructs expressing exons 9 and 10, together with the normal or mutant
      intron 9. A common C/T polymorphism within this branch point in intron 9 of the
      LDL-receptor gene does not affect mRNA splicing in vitro and is not associated
      with significant differences in mean plasma cholesterol concentration in a
      healthy population.

PMID- 8872474
TI  - The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a
      novel gene PRCC to the TFE3 transcription factor gene.
AB  - The specific chromosomal translocation t(X;1)(p11.2;q21.2) has been observed in
      human papillary renal cell carcinomas. In this study we demonstrated that this
      translocation results in the fusion of a novel gene designated PRCC at 1q21.2 to
      the TFE3 gene at Xp11.2. TFE3 encodes a member of the basic helix-loop-helix
      (bHLH) family of transcription factors originally identified by its ability to
      bind to microE3 elements in the immunoglobin heavy chain intronic enhancer. The
      translocation is predicted to result in the fusion of the N-terminal region of
      the PRCC protein, which includes a proline-rich domain, to the entire TFE3
      protein. Notably the generation of the chimaeric PRCC-TFE3 gene appears to be
      accompanied by complete loss of normal TFE3 transcripts. This work establishes
      that the disruption of transcriptional control by chromosomal translocation is
      important in the development of kidney carcinoma in addition to its previously
      established role in the aetiology of sarcomas and leukaemias.

PMID- 8872475
TI  - A family with Stickler syndrome type 2 has a mutation in the COL11A1 gene
      resulting in the substitution of glycine 97 by valine in alpha 1 (XI) collagen.
AB  - Stickler syndrome (hereditary arthro-ophthalmopathy) is the commonest inherited
      cause of retinal detachment and one of the commonest autosomal dominant
      connective tissue dysplasias. There is clinical and locus heterogeneity with
      about two thirds of families linked to the gene encoding type II procollagen
      (COL2A1). Families with Sticklers syndrome type 1 have a characteristic
      congenital vitreous anomaly and are linked without recombination to markers at
      the COL2A1 locus. In contrast families with the type 2 variety have a different
      vitreo-retinal phenotype and are not linked to the COL2A1 gene. Type XI collagen
      is a quantitatively minor fibrillar collagen related to type V collagen and
      associated with the more abundant type II collagen fibrils. A mutation in
      COL11A2, the gene for alpha 2 (XI) procollagen, has recently been found in a
      family described as having Stickler syndrome, although there was no ocular
      involvement. Here we show for the first time that a family with the full Type 2
      Stickler syndrome including vitreous and retinal abnormalities is linked to the
      COL11A1 gene and characterise the mutation as a Glycine to Valine substitution at
      position 97 of the triple helical domain caused by a single base G-->T mutation.
      These results are the first to provide confirmation that type XI collagen is an
      important structural component of human vitreous. They also support previous work
      suggesting that mutations in the genes encoding collagen XI can give rise to some
      manifestations of Stickler syndrome, but of these, only mutations in COL11A1 will
      give the full syndrome including the vitreo-retinal features.

PMID- 8872476
TI  - Role of late replication timing in the silencing of X-linked genes.
AB  - Cytosine methylation at promoter regions and late replication timing have both
      been implicated in the regulation of genes subject to X chromosome inactivation.
      Reported here are studies of X-linked gene replication in normal male and female
      cells as well as in cell hybrids that contain either a normal active X, a normal
      inactive X, or an inactive X chromosome that has been treated with the
      demethylating agent, 5-azacytidine (5aC). The relationship between replication
      timing and transcriptional activity was examined for XIST, XPCT, PGK1, HPRT, F9,
      FMR1, IDS, and G6PD, and earlier replication was generally found to be associated
      with increased transcriptional activity. The HPRT and G6PD genes in an untreated
      inactive X hybrid were among the few exceptions to this correlation in that they
      remain inactive, yet replicate earlier than their inactive X alleles present in
      normal human diploid cells. This condition of earlier replication timing may
      contribute to the high rates of 5aC-induced reactivation for HPRT and G6PD in
      this hybrid relative to other inactive X hybrids. Other anomalous cases include
      5aC-induced advances in replication time for genes such as XIST and F9 whose
      transcription was unaltered by treatment. These and other data support a model
      for regulation of X-inactivated genes that involves at least two levels of
      control: (i) large chromosomal domains are placed into a transcriptionally
      nonpermissive state by late replication and (ii) transcription is blocked at the
      local level by promoter methylation. In addition, our observations of continued
      XIST expression in 5aC-treated hybrids with reactivated genes indicates that such
      expression is not sufficient for the maintenance of X inactivation.

PMID- 8872477
TI  - The mouse Smcx gene exhibits developmental and tissue specific variation in
      degree of escape from X inactivation.
AB  - The Smcx gene is the first known example of a non-pseudoautosomal X-linked gene
      in mouse that normally escapes X chromosome inactivation. We have analysed the
      kinetics of escape at different stages of development, and in adult tissues. Our
      results demonstrate that Smcx exhibits partial escape from X inactivation in
      embryos, in extraembryonic lineages where paternally imprinted X inactivation
      occurs and also in adult tissues. The degree of escape in different tissues is
      highly variable, the level of transcript from the inactive X allele representing
      between 20% and 70% of the active X allele. Partial escape is also seen in clones
      derived from haematopoietic stem cells, suggesting that partial repression of the
      inactive X allele is at the level of individual cells. This contrasts with
      classical position effect variegation (PEV), where a given gene is either active
      or silent in a given cell and its clonal derivatives. We discuss the implications
      of these results with respect to mechanisms of X inactivation and escape.

PMID- 8872478
TI  - Tissue and lineage-specific variation in inactive X chromosome expression of the
      murine Smcx gene.
AB  - To understand how gene expression patterns are established on the inactive X
      chromosome during development, we have studied the murine gene Smcx, which is
      expressed from both the active and inactive mouse X chromosomes. In all tissues
      assayed, Smcx only partially escapes X inactivation, with expression levels from
      the inactive X allele approximately 30-65% that of the active X allele.
      Additionally, inactive X expression levels differed between extraembryonic and
      embryonic tissues and among different tissues from newborn and adult mice.
      Imprinted extraembryonic tissue had the lowest levels of inactive X Smcx
      expression, whereas the highest levels were in heart. These data suggest that the
      chromosomal basis of X inactivation differs among tissues, perhaps reflecting
      differences in the timing or regulation of inactivation in these cell lineages.

PMID- 8872479
TI  - Localization of a gene for Mobius syndrome to chromosome 3q by linkage analysis
      in a Dutch family.
AB  - Mobius syndrome (MIM no. 157900) consists of a congenital paresis or paralysis of
      the VIIth cranial nerve, frequently accompanied by paralysis of other cranial
      nerves, orofacial and limb malformations, defects of the musculoskeletal system
      and mental retardation. Although most patients are sporadic cases, familial
      recurrence is not rare. Different pedigrees suggest different modes of
      inheritance. We performed linkage analysis in a large family with autosomal
      dominantly inherited Mobius syndrome, consisting essentially of asymmetric
      bilateral facial pareses. After exclusion of the candidate region for Mobius
      syndrome on 13q12.2-q13, we localized the gene to chromosome 3q21-22, indicating
      genetic heterogeneity of Mobius syndrome. This heterogeneity is further proven by
      the exclusion of both loci in a second family with Mobius syndrome.

PMID- 8872480
TI  - Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p
      (CMT2D).
AB  - Clinical, electrophysiological and genetic linkage studies were performed on a
      large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2
      (CMT2) with 38 members of which 14 were affected. Onset of the disease was
      between 16 and 30 years of age with weakness and atrophy of the hands more severe
      than of the feet with slow progressive course in 12 patients. Deep tendon
      reflexes were absent in the upper extremities and decreased in the lower
      extremities. There was distal hypesthesia for touch, proprioception and vibration
      sense for the hands more than for the feet. Motor nerve conduction velocities
      showed normal values (48-53 M/s) with normal latencies (2-3 msec) and
      electromyography revealed signs of denervation. Genetic linkage analysis used 167
      short tandem repeat markers (STRPs) spaced throughout the 22 autosomes. Linkage
      to the short arm of chromosome 7 at 7p14 was found using the marker D7S435 (Z =
      4.83 at theta = 0). Flanking markers were D7S1808 and D7S1806 and the genetic
      distance between them was 6.8 cM. The multipoint linkage analysis gave a peek
      multipoint lod score of 6.89 between the markers D7S1808 and D7S435. Linkage
      analysis showed significantly negative lod scores (with values less than -2) with
      markers of chromosomes 1 and 3 where CMT axonal forms have been previously
      mapped. PFGE analysis indicated the absence of the CMT1A duplication. Our
      findings are consistent with a new genetic type of axonal CMT neuropathy
      designated by us as CMT2D. Potential candidate genes are multiple T-cell gamma
      receptor genes which map to the same cytogenetic interval as CMT2D neuropathy.

PMID- 8872481
TI  - Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1-q24.31.
AB  - Scapuloperoneal (SP) syndromes are heterogeneous neuromuscular disorders which
      are characterized by weakness in the distribution of shoulder girdle and peroneal
      muscles. SP syndromes can resemble facioscapulohumeral muscular dystrophy (FSH)
      due to scapular weakness or Charcot-Marie-Tooth disease (CMT) due to atrophy of
      peroneal muscles. Both neurogenic and myopathic SP syndromes have been described.
      Locus for the myopathic form of SP syndrome (scapuloperoneal muscular dystrophy,
      SPMD) has recently been assigned to chromosome 12q. We previously described a
      large New England kindred exhibiting an autosomal dominant neurogenic SP syndrome
      (scapuloperoneal spinal muscular atrophy, SPSMA). Disease expression was more
      severe and progressive in successive generations, which suggested genetic
      anticipation. We performed genetic linkage analysis of this family with
      microsatellite markers and excluded the loci for FSH, CMT, SPMD and SMA (spinal
      muscular atrophy) in our family. Linkage in our SPSMA family (lod score > 3) was
      established to seven microsatellite markers that map to chromosome 12q24.1
      q24.31. The highest lod score with two-point linkage analysis was 6.67 (theta =
      0.00) with marker D12S353. Multipoint analysis gave maximum lod scores of 7.38
      between D12S354 and D12S79, and also 7.38 between D12S369 and NOS1 (neuronal
      nitric oxide synthase). The gene for SPSMA lies within the 19 cM interval between
      D12S338 and D12S366. This report establishes a locus for the neurogenic form of
      SP syndrome approximately 20 cM telomeric to the one described for the myopathic
      form of SP syndrome.

PMID- 8872482
TI  - A novel locus for non-syndromic sensorineural deafness (DFN6) maps to chromosome
      Xp22.
AB  - Non-syndromic X-linked deafness is highly heterogeneous. At least five different
      clinical forms have been described, but only two loci have been mapped. Here we
      report a Spanish family affected by a previously undescribed X-linked form of
      hearing impairment. Deafness is non-syndromic, sensorineural, and progressive. In
      affected males, the auditory impairment is first detected at school age,
      affecting mainly the high frequencies. Later it evolves to become severe to
      profound, involving all frequencies for adulthood. Carrier females manifest a
      moderate hearing impairment in the high frequencies, with the onset delayed to
      the fourth decade of life. Deafness was assumed to be X-linked dominant, with
      incomplete penetrance and variable expressivity in carrier females. The family
      was genotyped for a set of microsatellite markers evenly spaced at intervals of
      about 10 cM. We found evidence of linkage to markers in the Xp22 region (maximum
      lod score of 5.30 at theta = 0.000 for DXS8036 and for DXS8022). The position of
      the novel deafness locus (DFN6) was refined by haplotype analysis. Mapping of the
      breakpoints in two critical recombinants allowed us to define an interval for
      DFN6, delimited by DXS7108 on the distal side and by DXS7105 on the proximal
      side, and spanning a genetic distance of about 15 cM.

PMID- 8872483
TI  - Processing and presentation of endocytically acquired protein antigens by MHC
      class II and class I molecules.

PMID- 8872484
TI  - Regulation of antigen processing and presentation to class I MHC restricted CD8+
      T lymphocytes.

PMID- 8872485
TI  - The endogenous pathway of MHC class II antigen presentation.

PMID- 8872486
TI  - Appreciating the complexity of MHC class II peptide binding: lysozyme peptide and
      I-Ak.

PMID- 8872487
TI  - H2-M3 restricted presentation of Listeria monocytogenes antigens.

PMID- 8872488
TI  - Reactivity and specificity of CD8+ T cells in mice with defects in the MHC class
      I antigen-presenting pathway.

PMID- 8872489
TI  - Serum levels of interleukins 2, 6 and 8, soluble interleukin-2 receptor and
      intercellular adhesion molecule-1 during treatment with interleukin-2 plus
      interferon-alfa.
AB  - In the present study we evaluated the haematological and immunological changes in
      4 patients with advanced melanoma and 6 patients with advanced renal cell
      carcinoma treated with subcutaneous interleukin (IL)-2 and interferon (IFN)-alfa
      2b. Serum samples taken before and during six weeks' courses of IL-2 plus IFN
      alfa were assayed for the presence of IL-2, soluble IL-2-receptor (sIL-2R),
      soluble intercellular adhesion molecule-1 (sICAM-1), IL-6 and IL-8. In addition,
      whole blood counts were taken. Eosinophilia occurred in all patients,
      lymphocytosis in 8 patients. The higher maximum level of IL-2 during treatment
      seemed to be connected to longer survival: it was a median of 578 pg/ml in the
      patients with a median survival of 7 months, and 1025 pg/ml in the patients who
      survived a median of 15 months. Conversely, an increase in sIL-2R was an
      unfavourable sign: it was a median of 8-fold and 3-fold in the patients with a
      median survival of 7 and 16 months, respectively. During treatment, sICAM-1
      levels paralleled with those of sIL-2R. There was major intraindividual and
      interindividual variation in serum IL-6 and IL-8 levels with no distinctive
      kinetic pattern. Thus, no definite conclusions could be drawn. However, it seems
      worthwhile to measure IL-2, sIL-2R and sICAM-1 during immunotherapy; their
      prognostic value should be further evaluated in a larger patient population.

PMID- 8872490
TI  - Immunological effects following administration of interferon-alpha in patients
      with chronic hepatitis C virus (cHCV) infection.
AB  - The immunological effects of interferon (IFN)-alpha administration were evaluated
      in 15 patients with cHCV infection. Individuals were treated with 6 MU of
      lymphoblastoid IFN-alpha three times a week for 6 months and with 3 MU three
      times a week for an additional 6 months. Patients were divided into responders
      (12 subjects) and nonresponders (3 subjects), respectively, according to alanine
      aminotransferase serum levels at the end of treatment. Before therapy (T0),
      absolute numbers of CD3+, CD4+, CD8+, CD14+ and CD16+ cells were significantly
      reduced in both groups when compared to normal values. At the same time, all
      patients displayed a profound decrease of phagocytosis and killing exerted by
      both polymorphonuclear cells (PMN) and monocytes (MO). However, MO Killing
      resulted to be normal in the responder group. With special reference to T cell
      function, T cell mediated antibacterial activity, using Salmonella typhi as a
      target, was also significantly reduced. After therapy (T12), in responder
      patients a significant increase of CD3+, CD4+, CD14+ and CD16+ cell absolute
      numbers was observed, while phagocytic and T cell functions were still depressed.
      Among the nonresponders, in two of three patients IFN-alpha administration gave
      rise to an increase (above normality) of CD3+, CD4+, CD8+, CD14+, CD16+ and CD20+
      cell absolute numbers, while in one patient the same markers dramatically dropped
      below normal range. In two patients, antibacterial activity was significantly
      augmented by IFN-alpha treatment, whereas in one patient no modification was
      observed. Finally, in the same patients IFN-alpha did not correct PMN and MO
      pretreatment deficits.

PMID- 8872491
TI  - Gamma interferon induced increases in intracellular cathepsin B activity in PMA
      primed THP-1 cells are blocked by inhibitors of protein kinase C.
AB  - Macrophage proteinases including cathepsin B (CB) are implicated in the tissue
      injury of inflammatory lesions. We have previously shown that interferon-gamma
      (IFN-gamma) increases intracellular levels of the lysosomal proteinase, CB, in
      THP-1 cell primed with phorbol 12-myristate 13-acetate (PMA). We have now
      examined the role of protein kinase C (PKC) in this effect. Following activation
      with PMA, the intracellular CB activity was significantly increased in the
      presence of 500 U/ml IFN-gamma. With the addition of protein kinase C (PKC)
      inhibitors bisindolylmaleimide, staurosporine, H-7, or phloretin a reversal of
      the effect of IFN-gamma was noted whereas the addition of the cyclic nucleotide
      dependent protein kinase inhibitors HA 1004, H-8, H-89, or cAMP-Dependent Protein
      Kinase (PKA) Inhibitor did not block the effect. Although diacylglycerol (DAG)
      did not replace PMA in the study. Diacylglycerol Kinase Inhibitor induced a more
      pronounced augmentation and PKC depletion inhibited the effect. This suggests
      that a PKC-dependent pathway is involved in the response of CB in PMA primed THP
      1 cells to IFN-gamma.

PMID- 8872492
TI  - Evaluation of interleukin-1 receptor antagonist (IL-1RA) and tumor necrosis
      factor binding protein (TNF-BP) in a rodent abscess model of host resistance.
AB  - Modulation of pro-inflammatory cytokine responses can alter the normal protective
      mechanisms against invading pathogens. The cytokines interleukin-1 beta (IL-1
      beta) and tumor necrosis factor-alpha (TNF-alpha) are crucial in the inflammatory
      cascade for upregulation of adhesion molecule expression, neutrophil recruitment,
      and additional cytokine induction. To determine if the cytokine antagonists
      interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor-binding
      protein (TNF-bp) alter host resistance mechanisms they were evaluated in a rodent
      abscess model. It has previously been shown that subcutaneous Staphylococcus
      aureus injections induce abscess formation in rats. These abscesses can be
      examined over a pre-determined time course for evaluation of size, severity and
      time to resolution. Treatment with immunosuppressive drug therapy can modify the
      normal course of abscess formation and/or resolution. IL-1ra and TNF-bp were
      administered either alone or in combination. Also, the effects of these cytokine
      antagonists in combination with dexamethasone were tested. Results indicated TNF
      bp at any dose examined did not adversely alter any parameter of abscess
      formation or resolution. In contrast, high doses of IL-1ra increased abscess
      severity, while more clinically relevant doses did not. Combination treatment
      with IL-1ra and TNF-bp did not alter abscess parameters above individual
      findings. Dexamethasone, given in combination with either cytokine antagonist,
      significantly increased severity grading scores above dexamethasone given alone.
      Overall the data indicated high dosing regimens of IL-1ra or TNF-bp only caused
      transient impacts on this host resistance model, while more clinically relevant
      doses did not impact any aspect of the abscess. These findings demonstrate that
      these anti-cytokine therapies do not alter general host resistance.

PMID- 8872493
TI  - Effect of DTC on humoral response of SRBC-immunized mice exposed to restraint
      stress. Comparison with calf thymus extract.
AB  - The studies were conducted on Balb/c mice exposed to restraint stress twice for
      12 h at 24 h intervals. Some of the experimental mice were immunized i.p. with
      sheep red blood cells (SRBC). The antigen was injected before the first exposure
      of the mice to restraint stress, or immediately after the second loading was
      ended. Sodium diethyldithiocarbamate (DTC) at a dose of 20 mg/kg or calf thymus
      extract (TFX) at a dose of 10 mg/kg were injected i.p. four times at 24 h
      intervals, before or after the exposure to restraint stress. In our experiment
      restraint stress drastically reduced the number of thymocytes and splenocytes as
      well as the weight ratio of the thymus and spleen and the changes sustained for
      10 days of the observation. Besides, humoral response of the restrained mice to
      SRBC was deteriorated, as the number of plaque forming cells (PFC) and anti-SRBC
      antibody titers (total and 2-mercaptoethanol resistant) decreased. The
      suppressive action of the stress on humoral response was weaker when the antigen
      injection preceded the first exposure of mice to restraint stress as compared
      with that observed when antigen stimulation took place immediately after the
      exposure of mice to stress. It has been found that DTC and TFX administered to
      mice either before or after the exposure to restraint stress effectively inhibit
      stress-induced immunosupression. The protective or immunomodulating action of the
      two drugs is expressed in accelerated and enhanced recovery of the spleen and
      thymus and in total or partial restoration of the humoral response to thymus
      dependent antigen. TFX, administered after the exposure of mice to restraint
      stress, proves to have a stronger protective and reconstructive impact on thymus,
      while DTC has a stronger restoring effect on the humoral response dependent on
      effector T lymphocytes. DTC administered immediately after the exposure of mice
      to restraint stress results in total restoration of humoral response to SRBC.

PMID- 8872494
TI  - Production of IL-1 beta and IL-6 by adherent spleen cells after the stimulation
      with lipopolysaccharides from Salmonella enteritidis strain.
AB  - Three different procedures were used to isolate lipopolysaccharides from the
      Salmonella enteritidis strain 477: phenol-water extraction with ethanol
      precipitation (LPS 1), phenol-water extraction with methanol precipitation (LPS
      2) and FPLC purification (LPS 1/1). Production of interleukin-1 beta (IL-1 beta)
      and interleukin-6 (IL-6) was observed in the supernatants of adherent spleen
      cells of BALB/c mice after the stimulation and cultivation of the cells. The
      quantity of IL-1 beta and IL-6 depended on the method of LPS isolation. The
      highest level of IL-1 beta was recorded at LPS 2, and of IL-6 at the stimulation
      of cells by means of LPS 1.

PMID- 8872495
TI  - Synergistic interaction between dehydroepiandrosterone and prednisolone in the
      inhibition of rat lymphocyte proliferation.
AB  - The interaction between dehydroepiandrosterone (DHEA) and prednisolone (PD) in
      the inhibition of rat lymphocyte proliferation was evaluated. The in vitro
      proliferative response of splenocytes from male Sprague-Dawley rats stimulated
      with phytohemagglutinin (PHA) was measured by the incorporation of 3H-thymidine
      into the DNA. DHEA and PD were added at the initiation of cultures individually
      and in various molar ratio combinations. The search for synergy, additivity or
      antagonism between the two compounds was performed by using the median-effect
      method of Chou and Talalay and Drewinko's statistical analysis. Both compounds
      individually inhibit the proliferation of PHA-stimulated rat lymphocytes. DHEA
      with an IC50 value of 13.4 microM was a thousand times less potent than PD which
      had an IC50 value of 5.4 nM. Synergy was observed between DHEA and PD. The
      intensity of the interaction appeared to be function of the molar ratio of the
      two drugs. The association of DHEA and PD could produce enhanced steroid effects
      in anti-inflammatory therapy.

PMID- 8872496
TI  - Spirulina platensis exposure enhances macrophage phagocytic function in cats.
AB  - Bronchoalveolar lavage macrophages isolated from cats were cultured on glass
      coverslips. Macrophages were exposed to a water-soluble extract of Spirulina
      platensis in concentration range of 0 to 60 micrograms per mL for two hours.
      Spirulina-extract exposure did not cause significant macrophage cytotoxicity over
      untreated control cultures. Macrophage monolayers from treated and control
      cultures were incubated with sheep red blood cells (SRBC) as well as viable
      Escherichia coli. The percentages of phagocytic macrophages for both of these
      particulate antigens were higher (a two-fold increase in SRBC phagocytosis and
      over 10% increase in Escherichia coli uptake) in cultures treated with various
      concentrations of Spirulina-extract. However, the numbers of either types of
      particles internalized by phagocytic macrophage were not different between the
      control and treated cultures. These data which showed that Spirulina platensis
      extract enhances macrophage phagocytic function imply that dietary Spirulina
      supplementation may improve the disease resistance potential in cats.

PMID- 8872497
TI  - Dietary Spirulina platensis enhances humoral and cell-mediated immune functions
      in chickens.
AB  - Cornell K-strain White Leghorns and broiler chicks were raised to 7 wks and 3 wks
      of age respectively, with diets containing various levels (0, 10, 100, 1,000 and
      10,000 ppm) of Spirulina platensis from day of hatch. Chicks in all treatment
      groups had comparable body weights. While bursal and splenic weights did not
      change, the K-strain chicks had larger thymuses (P < or = .05) over the controls
      (0 ppm group). No differences were observed in anti-sheep red blood cells
      antibodies during primary response. However, during secondary response, K-strain
      chicks in all Spirulina-dietary groups had higher total anti-SRBC titers with
      10,000 ppm group being the highest (6.8 Log2) versus the 0 ppm (5.5 Log2) group.
      In broiler chicks, a one Log increase in IgG (P < or = .05) was observed in
      10,000 ppm group over the controls. Similarly, chicks in 10,000 ppm Spirulina
      group had a higher PHA-P-mediated lymphoproliferative response over the 0 ppm
      controls. Macrophages isolated from both K-strain (10,000 ppm group) and broilers
      from all Spirulina groups had higher phagocytic potential than the 0 ppm groups.
      Spirulina supplementation at 10,000 ppm level also increased NK-cell activity by
      two fold over the controls. These studies show that Spirulina supplementation
      increases several immunological functions implying that a dietary inclusion of
      Spirulina at a level of 10,000 ppm may enhance disease resistance potential in
      chickens.

PMID- 8872498
TI  - Radiation-induced lung injury in vivo: expression of transforming growth factor
      beta precedes fibrosis.
AB  - Cytokine release from irradiated cells has been postulated to start soon after
      irradiation preceding detectable clinical and pathological manifestation of lung
      injury. The expression of transforming growth factor beta (TGF beta), a
      fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after
      the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation
      caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid
      peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state
      TGF beta mRNA expression as shown by whole lung northern blot assay paralleled
      the TGF beta protein expression in BAL fluid. The peak of TGF beta protein
      increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of
      inflammatory cells in BAL fluid, but preceded histologically discernable
      pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In
      conclusion. TGF beta and mRNA and protein upregulation preceded the radiation
      induced pulmonary fibrosis, suggesting a pathogenetic role in the development of
      radiation fibrosis.

PMID- 8872499
TI  - Relationship of the dose of intravenous gammaglobulin to the prevention of
      infections in adults with common variable immunodeficiency.
AB  - The objective was to assess clinical efficacy of 3 dosages of intravenous
      gammaglobulins to prevent infectious episodes in adult common variable
      immunodeficiency. We designed a randomized, double blind, dose-assessing study.
      The setting was at University Hospital, Out-patient Clinic. Our patients were
      twenty-one adult patients with common variable immunodeficiency. The measurements
      were comparative study of the number and severity of infections using 3 various
      dosages of intravenous gammaglobulins, each given monthly for M least 6 months.
      Results indicated four hundred and eighty-four infectious episodes occurred while
      giving 305 infusions of IVIG 200 mg/kg; 205 infectious episodes while giving 170
      infusions of 400 mg/kg and 436 infectious episodes while giving 247 infusions of
      600 mg/kg. The morbidity scores (infection/infusion) were 1.59, 1.21 and 1.77
      respectively (p - N/S). There was no significant difference in the severity of
      infections on the above 3 dosages, and no difference in the duration of infection
      free intervals. The conclusions resulted in no significant differences in
      morbidity in adult patients with common variable immunodeficiency treated in
      cross-over pattern with IVIG 200 mg/kg, 400 mg/kg and 600 mg/kg. Thus, high
      dosages of IVIG are not conferring better protection against infections in such
      patients.

PMID- 8872500
TI  - Effect of recombinant human interleukin 2 on neutrophil adherence to endothelial
      cells in vitro.
AB  - Human neutrophils were demonstrated to possess interleukin-2 receptor (IL-2R)
      beta and gamma chains, not alpha chain and the binding of IL-2 to the IL-2R beta
      chain on neutrophils plays an important regulatory role in neutrophil functions.
      We have investigated in this study the hypothesis that recombinant human IL-2
      (rhIL-2) can directly activate human neutrophils and increase their adherence to
      human umbilical vein endothelial cells (HUVEC). In an in vitro microtiter
      adherence assay, rhIL-2 significantly stimulated neutrophil adherence to HUVEC in
      a dose- and time-dependent manner, rhILI-2 concentration at 2000 u/ml and 2 hour
      incubation gave the best neutrophil stimulation. Treatment of neutrophils with
      rhIL-2 increased the expression of adhesion molecule CD18. Pretreatment of the
      stimulated neutrophils with a blocking monoclonal antibody to CD18 decreased but
      not completely blocked the adherence of neutrophils to HUVEC. These data suggest
      than rhIL-2 can directly stimulate and increase neutrophil adherence to HUVEC by
      enhancing the expression of CD18 and possibly other adhesion molecules on
      neutrophil surface. This may be a critical step in the early stage of the
      vascular leak syndrome (VLS) associated with high dose IL-2 therapy.

PMID- 8872501
TI  - Homologous serum increases fibronectin expression and cell adhesion in airway
      smooth muscle cells.
AB  - This study describes altered patterns of growth and upregulation of fibronectin
      expression of cultured canine airway smooth muscle cells grown in homologous
      serum, which provides a model of the vascular leakage occurring in asthma,
      compared to fetal bovine serum (FBS). Cells were incubated in increasing
      concentrations of serum (2.5-40%) for 72 hours. Both homologous serum and FBS
      caused cellular proliferation which reached a maximum increase at 2.5-5% serum
      concentration. Differences in the cellular responses to the two types of sera
      were noted at higher concentrations of sera. At a concentration of 40% FBS,
      airway smooth muscle cells increased in number by 307 +/- 16% (n = 5) compared to
      serum-free control cells, whereas in canine serum the increase in growth was
      significantly smaller, 239 +/- 25% (n = 7) (P < 0.05). Airway fibrocytes
      similarity treated increased in number by 256 +/- 43% (n = 3) in 40% FBS, but
      exhibited a reduction in cell number to 80 +/- 10% (n = 3) of controls in 40%
      homologous serum (P < 0.05). Smooth muscle cells demonstrated a dose-dependent
      increase in fibronectin expression when grown in homologous serum but not in FBS,
      suggesting phenotypic change occurred in these cells when exposed to homologous
      serum. These data suggest that the leakage of plasma in the asthmatic airway may
      trigger phenotypic change in both airway smooth muscle cells and airway
      fibrocytes leading to cellular proliferation and expression of extracellular
      matrix molecules. These in vitro changes are consistent with the histological
      findings in clinical asthma.

PMID- 8872502
TI  - Secretion of type-1-fimbriae binding proteins from human neutrophil granulocytes.
AB  - Granule matrix proteins secreted from human neutrophils after ionomycin
      stimulation were separated by SDS-PAGE, blotted onto a polyvinylidene diflouride
      (PVDF) membrane and overlaid with the mannose-binding lectin concanavalin A (Con
      A) or Escherichia coli bacteria exposing type-I-fimbriae. Four proteins of
      approximately 30, 40, 70 and 80 kD, respectively, derived from both the azurophil
      and the specific granules were shown to expose mannose-containing structures by
      binding of Con A. Such reactivity was also shown for a 90-kD protein from the
      light membrane fraction enriched in plasma membrane and secretory vesicles. When
      blots of granule matrix proteins were exposed to type-I-fimbriated bacteria, a
      total of seven proteins was recognized; four of the five Con A-binding proteins
      (40, 70, 80 and 90 kD) was detected also by the bacteria in addition to three
      proteins not detected by Con A (50, 60 and 100 kD). The role of the secreted type
      1-fimbriae binding proteins as anti-adhesin candidates is discussed.

PMID- 8872503
TI  - ICAM-1-, -2- and LFA-1-independent homotypic T cell aggregation induced by a
      novel activating monoclonal antibody targeting the murine Thy-1 molecule.
AB  - We have previously reported that the murine T cell line EL-4 has an aggregating
      phenotype, displaying homotypic aggregation (HTA) when exposed to monoclonal
      antibodies targeting specific cell surface molecules such as leukocyte function
      associated antigen-I (LFA-1). We have used this property of EL-4 cells to isolate
      additional HTA-inducing MAb by screening a panel of hybridomas that were
      generated from rats immunized with EL-4 cells. We have isolated a novel anti-Thy
      1 MAb (termed FF-10) that is a powerful inducer of HTA in EL-4 cells. In addition
      to induction of HTA, FF-10 also induces splenocyte proliferation but inhibits
      anti-CD3-driven T cell proliferation. Thy-1-induced HTA cannot be blocked with
      MAb targeting intercellular adhesion molecule-I and -2 (ICAM-1, ICAM-2) or LFA-1.
      Thus, the FF-10 MAb represents a novel and unique tool to investigate the diverse
      roles of the murine Thy-I molecule in T cell activation, proliferation and
      apoptosis.

PMID- 8872504
TI  - Presence of immunocytes and sulfidopeptide leukotrienes in the inflamed guinea
      pig distal colon.
AB  - This study examined whether the immunocyte recruitment associated with a mild
      inflammatory state induced by acetic acid would produce detectable sulfidopeptide
      leukotriene (LT) levels from colonic tissues or in dialysates. Histological
      examination and measurements of peroxidase activities of inflamed tissues
      indicated edema, hyperplasia and neutrophil infiltration. Significant elevated
      LTB4 and prostaglandin E2(PGE2) levels were found but only slight elevations in
      sulfidopeptide LTs occurred. A slight elevation in eosinophil peroxidase
      indicated that eosinophil infiltration also occurred. The increase in
      sulfidopeptide LT levels appeared insufficient by itself to alter secretory
      responses in the distal colon. However, combined with other immunocyte products
      such as PGs, the sulfidopeptide LTs may influence the symptomology of
      inflammatory bowel disease.

PMID- 8872505
TI  - Priming of NADPH oxidase by tumor necrosis factor alpha in patients with
      inflammatory and autoimmune rheumatic diseases.
AB  - Oxidative damage caused by oxygen free radicals from activated phagocytes
      contributes to the pathology of arthritis. The present study evaluates the
      activity of NADPH oxidase of neutrophils and monocytes from patients suffering
      from various inflammatory and autoimmune rheumatic disease. Production rates of
      reactive oxygen species [ROS] of neutrophils and monocytes from rheumatic
      patients are compared to those of healthy controls and non rheumatic disease
      controls and correlated with the plasma levels of tumor necrosis factor alpha, C
      reactive protein and the sedimentation rates of erythrocytes. There was a two- to
      eightfold increase in phagocytic superoxide production in rheumatic patients,
      when compared to healthy subjects or patients with non-rheumatic internal
      diseases [p < 0.005]. The enhanced NADPH oxidase-dependent superoxide generation
      correlated well with elevated levels of tumor necrosis factor alpha [TNF-alpha]
      in plasma [p = 0.005], suggesting a causal relation. There was no correlation
      with the plasma levels of C-reactive protein and a weak though significant
      correlation with the sedimentation rates of erythrocytes [p = 0.043]. Removal of
      circulating TNF-alpha by dialysis of patients blood and inhibition of NADPH
      oxidase by prednisolone treatment normalized elevated ROS production to the
      levels of healthy controls and correlated with the clinical improvements. Our
      data support the hypothesis of a central role for TNF-alpha during the
      development of arthritis. The chemiluminescence assay described here may be
      useful as a convenient screen and as a potential follow up procedure for
      individual patients with rheumatic diseases.

PMID- 8872507
TI  - Facing the future: drug discovery reconsidered.

PMID- 8872506
TI  - Activation of phospholipase D is an early event in integrin-mediated signalling
      leading to phagocytosis in human neutrophils.
AB  - Integrin receptors on human neutrophils mediate adhesion and phagocytosis. These
      functions are linked to a signal-transduction cascade that rearranges the
      cytoskeleton. The intention of this study was to clarify how activation of
      phospholipase D (PLD) is coupled to the complement receptor three (CR3,
      CD18/CD11b)-mediated ingestion process. Carbobenzyloxy-leucine-tyrosine
      choloromethylketone (zLYCK) inhibited PLD activation induced by complement
      opsonized yeast particles (COYP) by 39%. Phagocytosis of these particles was
      reduced by zLYCK to the same extent. Anti-CD18-antibodies bound to protein A
      positive Staphylococcus aureus bacteria induced a significant PLD activation.
      These particles were not ingested which implicates that CR-mediated ingestion per
      se is not required to induce PLD activity. Cytochalasin B-treatment, which blocks
      actin reorganization, partly reduced COYP-mediated PLD activity, but had no
      effect on activity caused by anti-CD18-coated particles. This excludes activation
      of PLD to be a secondary event, but rather an early signal in the phagocytic
      uptake prior to actin reorganization. These data suggest an important and early
      role for PLD in integrin-mediated phagocytosis.

PMID- 8872508
TI  - A study of the antiulcer mechanisms of propranolol in rats.
AB  - Although propranolol has been shown to protect against ethanol and stress
      ulceration, the antiulcer mechanisms are still unclear. The present study
      examined the antiulcer mechanisms of propranolol in three different types of
      ulceration induced respectively by ethanol (60%), indomethacin (30 mg/kg) and
      stress (cold-restraint). Propranolol pretreatment in the highest dose (10 mg/kg)
      given either intraperitoneally (i.p.) or orally (p.o.) prevented gastric mucosal
      damage in these three ulcer models. The three doses of the drug (2.5, 5 or 10
      mg/kg) dose-dependently decreased systemic blood pressure which was accompanied
      by a reduction of gastric mucosal blood flow. These findings suggest that the
      protection was unrelated to an improvement of local circulation in the stomach.
      However, propranolol preserved the mucus levels in the three types of ulcer
      models. The beta-adrenoceptor blocker also increased the basal gastric mucosal
      potential difference. These findings indicate that propranolol strengthens the
      mucosal barrier by the preservation of mucosal mucus and enhancement of the
      mucosal integrity in the stomach.

PMID- 8872509
TI  - Interaction between enoxacin, a new antimicrobial, and nimesulide, a new non
      steroidal anti-inflammatory agent in mice.
AB  - Convulsions induced by the combination of enoxacin, a new antimicrobial, and
      nonsteroidal anti-inflammatory drugs including nimesulide, ketoprofen,
      pranoprofen and loxoprofen sodium, were investigated in mice. The oral
      administration of nimesulide alone induced clonic convulsions at more than 300
      mg/kg. The oral administration of ketoprofen, pranoprofen or loxoprofen sodium
      induced no convulsion up to 1000 mg/kg, 500 mg/kg and 600 mg/kg, respectively,
      and that of enoxacin induced no convulsion at more than 5000 mg/kg. The
      combination of nimesulide at 200 mg/kg and enoxacin at 400 mg/kg induced no
      convulsion. In contrast, the combination of enoxacin at 100 mg/kg and either
      ketoprofen at 125 mg/kg or pranoprofen at 500 mg/kg induced clonic convulsions,
      while that of enoxacin at 400 mg/kg and loxoprofen sodium at 600 mg/kg induced no
      convulsion. These results suggest that the combination of nimesulide and enoxacin
      may possibly induce few or less convulsions in the clinical setting.

PMID- 8872510
TI  - Effect of chronic sciatic nerve lesion on the neurogenic inflammatory response in
      intact and acutely injured denervated rat skin.
AB  - A supersensitivity to the neuropeptide substance P (SP) has been shown to develop
      in post-terminal membranes of many denervated tissues. This study examined
      changes in the sensitivity of post-terminal vascular receptors to SP and
      calcitonin gene-related peptide (CGRP) in rat skin microvasculature following
      sciatic nerve section. In anaesthetised rats, 0.5 cm of sciatic nerve in the
      right mid-thigh region was removed. Two weeks later, SP (100 microM) and sodium
      nitroprusside (SNP, 1 mM), a direct smooth muscle vasodilator, were introduced
      into denervated intact footpad skin, via the electrophoresis technique. Laser
      doppler flowmeter was used to record changes in relative blood flow in the rat
      hind footpad. The results showed a significant increase in SP response over
      controls and slight increase in smooth muscle reactivity as determined by an
      increase in the vascular response to SNP. In another set of experiments, the
      sensitivity of post-terminal receptors was examined over a 4 weeks period in an
      acutely injured footpad skin of sciatic nerve lesioned rats. A vacuum-induced
      blister was raised on the hind footpad and SP, CGRP (each at 1 microM) or SNP
      (100 microM) were superfused over the blister base. In nerve lesioned rats, using
      the acutely injured footpad skin model, the results showed a reduction in the
      vascular responses to SP, CGRP and SNP. The response to SP continued to decrease
      over time reaching 22% of control values by 4 weeks. Responses to SNP and CGRP
      were reduced to 53% and 45% respectively by 2 weeks and then improved to 75% of
      control values by 4 weeks. Possible contributions of sympathetic efferents and
      the saphenous nerve to these reduced responses in acutely injured skin of nerve
      lesioned rats were examined using guanethidine (50 mg/kg i.p.) or sectioned
      saphenous nerve respectively. These procedures did not significantly modify the
      reduced vascular responses in the blister base of lesioned rats. Possible
      activation of endogenous opioids and/or the release of endothelin due to blister
      induction in nerve lesioned rats was examined using naloxone and the endothelin
      receptor antagonist, BQ-123, respectively. Treatment with naloxone increased SP
      response in lesioned rats to 41% of control value with no change in smooth muscle
      reactivity. BQ-123 significantly increased the responses to SP and SNP to 51% and
      100% of their own control values respectively. It is concluded that
      supersensitivity of post-terminal vascular receptors develops in intact skin
      following chronic nerve lesion. On the other hand, acute injury of the denervated
      skin area induces activation of endogenous inhibitory modulatory mechanisms that
      masks this supersensitivity.

PMID- 8872511
TI  - Interleukin-8 (IL-8) is a major neutrophil chemotaxin from human alveolar
      macrophages stimulated with staphylococcal enterotoxin A (SEA).
AB  - Since Staphylococcus aureus is an important human pathogen, and infection of the
      lungs is characterized by neutrophil infiltration we studied the role of a
      staphylococcal toxin, enterotoxin A (SEA) on the synthesis and secretion of IL-8
      by human alveolar macrophages. As SEA concentration was increased, the IL-8
      accumulation in the macrophage conditioned medium increased. The concentration of
      mRNA encoding IL-8 was also elevated in the macrophage in response to increases
      in SEA concentration. Although the monocytic cell line U937 was able to respond
      to SEA and secrete IL-8, treatment with PMA prior to SEA stimulation increased
      the IL-8 accumulation around fifty fold indicating that maturation of the
      undifferentiated cell to a more macrophage-like cell facilitated IL-8
      accumulation. Stimulating human alveolar macrophages with high concentrations of
      SEA caused an increase in IL-1 accumulation. However, when the cells were
      incubated with SEA in the presence of IL-1 receptor antagonist, there was no
      decrease in IL-8 accumulation. Addition of a neutralizing anti-IL-8 monoclonal
      antibody to the culture medium of SEA-stimulated macrophages significantly
      reduced the neutrophil chemotactic activity of the medium. These studies showed
      that IL-8 is a major neutrophil chemotaxin from human alveolar macrophages
      stimulated with SEA.

PMID- 8872512
TI  - Peptide inhibitor of interleukin-8 (IL-8) reduces staphylococcal enterotoxin-A
      (SEA) induced neutrophil trafficking to the lung.
AB  - Staphylococcal enterotoxin A (SEA) is a superantigen, produced by some strains of
      Staphylococcus aureus (S. aureus), which can cause a variety of clinical
      manifestations ranging from food poisoning to shock. SEA can also stimulate human
      alveolar macrophages to produce interleukin-8 (IL-8), a member of the alpha
      chemokine subfamily that activates and is chemotactic for neutrophils. In these
      studies we showed that in rabbits, intravenous SEA significantly decreased the
      circulating white blood cell population from a baseline value of 6409 +/- 2027 x
      10(3) cells/ml to 1943 +/- 862 x 10(3) cells/ml in 7 h. There was a concommitent
      increase in IL-8 in the circulating plasma (baseline: 60 +/- 34 pg/ml, 7 h post
      SEA: 109 +/- 64 pg/ml). The increase in circulating IL-8 was accompanied by a
      much greater increase in the IL-8 concentration of the epithelial lining fluid
      (ELF) where the IL-8 increased from 0.05 +/- 0.08 ng/ml (control) to 13.8 +/- 9.3
      ng/ml (SEA treated). The increase in IL-8 concentration in the alveolar spaces
      was paralleled by an increase in both the percentage of neutrophils (1.4 +/- 0.9%
      (control) to 26.0 +/- 10.8% (SEA treated)) and total number of neutrophils (0.04
      +/- 0.02 x 10(6)/ml (control) to 4.8 +/- 3.3 10(6)/ml (SEA treated) in the
      airspaces, and the numbers of neutrophils in the ELF correlated with the IL-8
      concentration r = 0.62, p = 0.006). When antileukinate, a hexapeptide which
      inhibits the binding of IL-8 to neutrophils, was administered to animals
      receiving SEA, the IL-8 concentration in the ELF (14.8 +/- 10.7 ng/ml) was not
      significantly different from the concentration of IL-8 in those animals receiving
      SEA alone). However, both the percentage of neutrophils (9.5 +/- 3.2%), and the
      total number of neutrophils (1.3 +/- 1.0 x 10(6)/ml) in the ELF following SEA and
      antileukinate administration was significantly lower than in animals which only
      received SEA (p < 0.05). The findings suggest that SEA released into the
      circulation during a Staphylococcal infection can cause an inflammatory reaction
      in the lung. Since this reaction is at least partially mediated by IL-8,
      antileukinate may have pharmacologic potential in reducing the inflammatory
      reaction.

PMID- 8872513
TI  - Monocytes and lymphocytes as active participants in the pathogenesis of
      experimental shock.
AB  - We investigated the role played by monocytes and lymphocytes in the pathogenesis
      of experimental shock. Splanchnic artery occlusion (SAO) shock was induced in
      anaesthetized rats by clamping splanchnic arteries for 45 min followed by
      reperfusion. Sham operated animals were used as controls. SAO shocked rats had a
      decreased survival time (80 +/- 11 min, while sham shocked rats survived more
      than 4 h), increased serum (248 +/- 21 U/ml) and macrophage (145 +/- 15 U/ml)
      levels of TNF-alpha, enhanced myeloperoxidase (MPO) activity in the ileum (3.38
      +/- 0.2 U x 10(-3)/g tissue), decreased number of monocytes, lymphocytes and
      neutrophils and a profound hypotension. In addition we found an increased
      expression of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium
      and a reduced percentage of VLA-4 positive monocytes and lymphocytes. Inhibition
      of TNF-alpha synthesis, reversed the increased endothelial expression of VCAM-1,
      increased the percentage of integrin VLA-4 positive leukocytes and improved
      monocyte, lymphocyte and neutrophil count. Furthermore a passive immunization
      with specific antibodies raised against VCAM-1 (2 mg/kg, i.v. 3 h before SAO)
      increased survival, reduced MPO activity in the ileum (0.034 +/- 0.04 U x 10(
      3)/g tissue) and improved mean arterial blood pressure. Our data suggest that
      monocytes and lymphocytes participate in the pathogenesis of splanchnic ischaemia
      reperfusion injury and may amplify the adhesion of neutrophils to peripheral
      tissues.

PMID- 8872514
TI  - Factors influencing the acid-base changes in the air-pouch exudate following
      carrageenan induced inflammation in rats.
AB  - The interactions between the acid-base variables that contribute to exudate
      acidosis were studied in the subcutaneous air-pouch after carrageenan injection
      in rats. We studied the concurrent changes of exudate gases (PCO2 and PO2), main
      ions ([Na+], [K+], [Ca2+], [Mg2+], [Cl-] and [Lac-]), inorganic phosphate (P(i))
      and albumin in acutely inflamed rats (4, 8, 12, 24 and 48 h of inflammation). A
      notable hypercapnia was found in the exudate after only 8 h (exudate PCO2 = 64.3
      +/- 2.9 mm Hg) but this hypercapnia decreased after 48 h (32.9 +/- 12.7 mm Hg),
      coincident with the greatest increase in exudate cells. With respect to the
      metabolic acid-base variables, the most important changes found were a parallel
      decrease in the strong ion difference ([SID]) and exudate pH, as well as
      increases in the exudate weak acid buffers ([ATOT]) due to albumin and inorganic
      phosphate (P(i)) increases. However, after 12 h, the exudate acidosis was stable
      at around pH 7. A similar acid pH was obtained after 24 h of inflammation when
      the carrageenan solution injected was previously adjusted to a physiological pH
      (7.4). This pH, analogous to that of the exudate, was the result of compensation
      by the acid-base independent variables, a fact which suggests that acid pH may be
      a beneficial condition for cells taking part in inflammatory processes.

PMID- 8872515
TI  - Substrate specificity and inhibitor profile of human recombinant p56lck from a
      baculovirus expression vector.
AB  - p56lck, a member of the src family of non-receptor protein receptor kinases, is
      required for normal signal transduction through the T cell receptor.
      Inappropriate T cell activation and proliferation has been identified as an early
      event in auto-immune disease-agents which control T cell activation through
      modulation of p56lck kinase activity could therefore be potential therapeutic
      agents for a range of pathological conditions. To identify p56lck inhibitors, we
      have established an assay system suitable for the high throughput screening of
      compound libraries. The assay uses enzyme purified from baculovirus infected SF9
      cells, and a novel peptidic substrate identified by L. Cantley from a degenerate
      combinatorial peptide library. We have used this assay system to screen a number
      of different compounds as potential inhibitors of p56lck. In addition, peptides
      based on the substrate sequence were also tested to identify a sequence that
      could be used in the rational design of peptide inhibitors of p56lck.

PMID- 8872516
TI  - Determination of bradykinin-(1-5) in inflammatory exudate by a new ELISA as a
      reliable indicator of bradykinin generation.
AB  - We have developed an ELISA for BK-(1-5) (Arg1-Pro2-Pro3-Gly4-Phe5). In rat
      carrageenin-induced pleurisy, in which a plasma exudation peak was observed 5 h
      after carrageenin, BK levels in the exudates were negligible (< 60 pg/rat). BK-(1
      7) (des-Phe8-Arg9-BK) was detectable (900-400 pg/rat) over the entire course of
      the inflammation. However, a larger amount of BK-(1-5) was detectable in
      association with the increase in plasma exudation, showing a peak (8800 +/- 1200
      pg/rat) 3 h after carrageenin. Bromelain (10 mg/kg, i.v.) and soy bean trypsin
      inhibitor (0.3 mg/rat, intra-pleural) significantly reduced BK-(1-5) levels (by
      60-93%, 3, 7 and 19 h after carrageenin) and plasma exudation rates (by 61-74%, 3
      and 7 h after carrageenin). Dexamethasone (0.3 mg/kg, i.p.) reduced BK-(1-5)
      levels (by 78%) and decreased plasma exudation (by 70%) 3 h after carrageenin. In
      nasal allergy patients, antigen challenge of nasal mucosa elevated BK-(1-5)
      levels and active kallikrein levels in nasal washes. These results verify that BK
      (1-5) determined by ELISA is a good indicator for release of kinins in vivo.

PMID- 8872517
TI  - Skin mast cell releasability in dogs with atopic dermatitis.
AB  - Isolated dermal mast cells from atopic dogs are a valuable tool for the analysis
      of their functional properties in atopic dermatitis. We have characterized the
      histamine secretory pattern of mast cells enzymatically dispersed from the skin
      of dogs naturally suffering from this condition. The total histamine content
      found per isolated skin mast cell was higher in the allergic dogs than in
      nonatopic (control) animals (8.7 pg/mast cell versus 5.2 pg/mast cell). This
      phenomenon together with the well known higher concentration of skin mast cell
      number in atopic dermatitis lesions might account for the observed increase in
      local histamine concentration (15.0 micrograms/g versus 9.0 micrograms/g). Atopic
      dog-derived mast cells were highly reactive to both non-immunological (ionophore
      A23187) and an immunological-like (concanavalin A) stimulus. Furthermore,
      histamine net release induced by concanavalin A (1 mg/ml) stimulation was clearly
      enhanced in the atopic dogs (33.3% net release versus 15.4% in controls). These
      results have not been described in dermal mast cells dispersed from the skin of
      individuals with atopic dermatitis and clearly support the hypothesis that mast
      cells play a major role in causing and possibly modulating atopic dermatitis,
      through enhanced sensitivity or releasability. However, whether these two
      phenomena are primary abnormalities of atopic dermatitis, or only secondary
      changes, remains undetermined.

PMID- 8872518
TI  - Release of histamine in whole blood by oxygen radicals: division between specific
      and unspecific processes.
AB  - Oxygen derived free radicals are involved in many pathological processes such as
      postischemic reperfusion injuries, hepatotoxicity of drugs and inflammatory
      processes. Thereby these oxygen radicals induce lipid peroxidation and
      perturbation of cellular membranes. The aim of our present study was to determine
      whether oxygen radicals generated by the xanthine oxidase/ hypoxanthine system
      cause a release of histamine in human blood cell cultures. Stimulation of blood
      cell cultures with oxygen radicals induced a histamine liberation which was
      mainly due to calcium independent processes during the first 30 min, whereas then
      calcium requiring processes took part in the release of histamine. The regulation
      of the leukocyte selection LECAM-1 was altered by oxygen radicals whereas
      histamine, which is known to modulate vascular selectin expression, did not
      affect the expression of LECAM-1. Our data indicate that oxygen radicals induce a
      direct calcium independent release of histamine which is due to membrane
      pertubating processes during the first phase but also induce a specific reaction
      leading to a further indirect histamine liberation which is probably mediated by
      PAF.

PMID- 8872519
TI  - The role of endoscopic ultrasound in pancreatic disorders.

PMID- 8872520
TI  - Sphincter of Oddi dysfunction.
AB  - Evidence continues to accumulate indicating that sphincter of Oddi dysfunction
      may give rise to cholestasis, pancreatitis, or upper abdominal pain syndromes.
      Diagnosis of such dysfunction may be inferred from noninvasive tests or more
      precisely defined by manometric studies. Both the biliary and pancreatic
      sphincters are commonly involved. If medical therapy is ineffective, sphincter
      ablation via endoscopy or laparotomy should be considered for highly symptomatic
      patients. Complication rates of invasive techniques remain relatively high and
      risk:benefit ratio should be carefully considered. Future research as to
      etiology, more defined pathophysiology, more accurate noninvasive evaluation, and
      optimal therapies are awaited.

PMID- 8872521
TI  - "Mass-forming" pancreatitis masquerades as pancreatic carcinoma.
AB  - CONCLUSION: When a patient with a hypervascular pancreatic mass has a history of
      alcoholism and pancreatitis, and normal serum levels of CA 19-9, mass-forming
      pancreatitis should be kept in mind as a differential diagnosis of pancreatic
      carcinoma. BACKGROUND: Chronic and/or acute pancreatitis sometimes produces a
      pancreatic mass; and differentiation from pancreatic carcinoma is of clinical
      importance. METHODS: A total of 13 Japanese patients with mass-forming
      pancreatitis were retrospectively reviewed in order to clarify clinical features
      which can differentiate between mass-forming pancreatitis and pancreatic
      carcinoma. RESULTS: Six of the 13 patients had a history of chronic pancreatitis
      or acute pancreatitis from 8 mo to 11 yr previously. Eleven patients were
      alcoholic. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels
      were within normal limit in 9 of 12 patients examined and in all 12 patients
      examined, respectively. The pancreatic mass was located in the head of the
      pancreas in 9 patients, in the body in 1 and in the tail in 3. The mean greatest
      diameter of the mass was 2.8 cm. Six of the 13 pancreatic masses were hypoechoic
      by ultrasonography. Ten of the 13 pancreatic masses were of low-density by
      computed tomography. Two of the five masses examined were hypervascular at
      arterial and/or venous phase by angiography. Significant factors differentiating
      from pancreatic carcinoma were age, alcoholism, history of pancreatitis, serum
      levels of CA 19-9 and hypervascularity. Follow-up ultrasonography and/or computed
      tomography showed diminution of the mass in 1 to 2 mo in four patients, together
      with decrease of serum carcinoembryonic antigen and/or carbohydrate antigen 19-9
      levels in two of the four patients.

PMID- 8872522
TI  - Eating habits and pancreas cancer.
AB  - BACKGROUND: The eating habits of Japanese people are changing, which may have
      something to do with the increase in pancreas cancer in Japan. METHODS: Chiefly
      from the viewpoint of the eating habits, we investigated the etiological factors
      of this cancer through a community-based case-control study, employing 141 cases
      and 282 controls (two for each case) matched for sex, age, and place of
      residence, and through an ecologic study using the official reports of food
      consumption and deaths from this cancer in Hokkaido Prefecture. RESULTS: The case
      control study showed that intake of meats and animal viscera increased the risk
      of this cancer. On the other hand, vegetables and the traditional Japanese foods,
      e.g., tofu, deep-fried tofu, raw fish, and tempura, reduced the risk. The
      controls took more of the traditional Japanese foods than the cases. The ecologic
      study showed there were significantly negative correlations between the annual
      consumption of plant foods/plant protein and the annual crude mortality of
      pancreas cancer. CONCLUSION: The traditional Japanese foods, which include many
      plant foods, are preventive against the occurrence of pancreas cancer.

PMID- 8872523
TI  - Establishment of an experimental liver metastasis model by intraportal injection
      of a newly derived human pancreatic cancer cell line (KLM-1).
AB  - CONCLUSION: It is suggested that this liver metastasis model formed by a highly
      metastatic variant (KLM-1) is valuable for the study of the liver metastatic
      processes of human pancreatic cancer. BACKGROUND: Liver metastasis in the early
      postoperative period is one of the causes for the poor prognosis of patients with
      resected pancreatic cancer. Therefore, it is necessary to establish an
      experimental model to study the mechanisms of liver metastasis in pancreatic
      cancer. METHODS: Human pancreatic cancer cell lines (PK-1, PK-9, and KLM-1) were
      injected into the portal vein of nude mice with or without pretreatment with
      antiasialo GM1, and colonies of liver metastases were counted for comparison of
      metastatic ability of these cell lines. Biological and histopathological
      characteristics of the highly liver metastatic cell line (KLM-1) were compared
      with its parent cell line (PK-1). RESULTS: PK-1 cells and PK-9 cells rarely
      formed liver metastasis foci, but pretreatment with antiasialo GM1 promoted liver
      metastasis. KLM-1 cells formed liver metastases at the rate of 70% even without
      antiasialo GM1 pretreatment. KLM-1 cells had such biological characteristics as
      short doubling time, short lag phase, and resistance to NK cytotoxicity. After
      intraportal injection of 125I-labeled KLM-1 cells, radioactivity as well as
      micrometastases were detected in the liver at 72 h.

PMID- 8872524
TI  - Mutagenic activation of N-nitrosobis(2-oxopropyl)amine by pancreatic juice and
      assessment of its ductal tumorigenicity following intraductal administration in
      dogs.
AB  - CONCLUSION: The results suggest that systemic administration (s.c. and i.p.) of
      BOP induces liver damage due to BOP itself and/or its metabolites which might be
      formed in the liver and that interaction of BOP itself in the pancreatic duct
      with pancreatic juice plays an important role for pancreatic duct tumorigenicity.
      METHODS: Mutagenic activation and pancreatic duct tumorigenicity of N-nitrosobis
      (2-oxopropyl)amine (BOP) administered s.c., i.p., and i.d. were studied in dogs.
      RESULTS: Following i.p. administration of BOP, N-nitroso(2-hydroxypropyl) (2
      oxopropyl)amine (HPOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP), but not BOP,
      were detected in pancreatic juice, while following i.d. administration, only BOP
      was detected. The pancreatic juice of one dog that received 100 mg of BOP i.d.
      showed positive mutagenicity towards Salmonella typhimurium TA100, but the
      pancreatic juice of two dogs that received 100 mg of BOP i.p. was not mutagenic.
      BOP showed clear mutagenicity in the presence of pancreatic juice from untreated
      dogs, but the pancreatic juice could not activate HPOP and BHP to mutagens. BOP
      administered sc for 2 wk (total dose: 600 mg) induced clinical toxicity, nausea,
      vomiting, and loss of appetite at 10 wk. BOP administered i.p. for 4 mo (total
      dose: 2000 mg) induced liver damage at 6 mo, but no pancreatic injury. BOP
      administered i.d. for 6.5 or 12 mo (total dose: 2500 or 4700 mg, respectively)
      induced papillary hyperplasia and dysplasia of duct epithelial cells and ductal
      proliferation with fibrosis.

PMID- 8872525
TI  - The influence of acute ethanol ingestion on phospholipase D activity in rat
      pancreas. An in vitro and in vivo study.
AB  - CONCLUSION: Since phosphatidic acid (PA), a product of phospholipase D(PLD), is
      known as a second messenger probably involved in cell proliferation and
      differentiation, our results potentially suggest a new mechanism for pancreatic
      tissue injury after ethanol ingestion. BACKGROUND: The mechanisms by which
      ethanol causes pancreatic injury are still not clear. In vitro studies have
      suggested a relationship of PLD to ethanol metabolism. This study was undertaken
      to establish the involvement of PLD in ethanol metabolism in isolated pancreatic
      acini and to determine the influence of acute ethanol ingestion on PLD activity
      in pancreas and pancreatic growth after cerulein (Ce) infusion. METHODS:
      Dispersed pancreatic acini prelabeled with 3H myristic acid were incubated with
      500 pM Ce in the presence of different concentrations of ethanol; then labeled PA
      and phosphatidylethanol (PEt) production were measured under the same
      experimental conditions. For in vivo study, male rats were infused with Ce (0.25
      microgram/kg/h) or saline; 1 h before infusion, animals were treated with 40%
      ethanol (5 g/kg p.o.) or saline, respectively. After 1, 2, and 48 h of Ce
      infusion, rats were killed; dispersed pancreatic acini were then prepared and PLD
      activity was measured. Pancreatic weight, protein, RNA, and DNA content were also
      established. RESULTS: The production of PEt in vitro after Ce stimulation was
      significantly elevated with 1% ethanol in the medium. In the presence of
      different concentrations of ethanol (0.5-2%), a significant inhibition of PA
      accumulation in in vitro experiments was observed. The decrease of PA
      accumulation with ethanol was parallel to the increase of PEt production under
      the same experimental conditions. PLD activity was significantly elevated after 1
      and 2 h of Ce infusion (116 and 105%, respectively), reaching control value after
      48 h. Acute ethanol ingestion significantly diminished PLD activity after 1 and 2
      h. After 48 h of Ce infusion, a significant increase in pancreatic weight,
      protein, RNA, and DNA content in pancreatic tissue was found. Ethanol was not
      able to influence pancreatic weight, proteins and RNA content. However, it had
      the potency to diminish DNA content after 48 h of Ce infusion.

PMID- 8872526
TI  - Microsphere distribution in the pancreas of anesthetized rats. Alloxan stimulates
      the blood flow to all islets whereas glucose only affects the blood perfusion of
      a subgroup of islets.
AB  - CONCLUSION: Islet blood flow stimulation induced by alloxan leads to an increased
      blood perfusion in all islets, whereas glucose induces a flow increase only in a
      subgroup of islets. BACKGROUND: The aim of the present study was to investigate
      if an increased islet blood flow was associated with an enhanced total number of
      perfused islets, or whether only a subgroup of the islets increased their blood
      flow. METHODS: For this purpose, the whole pancreatic and islet blood flow was
      measured with a microsphere technique (4.5 x 10(5) microspheres/kg body wt) in
      anesthetized Sprague-Dawley rats. Blood flow measurements were made 3 min after
      an i.v. injection of 1 mL of saline, alloxan (75 mg/kg body wt), or D-glucose
      (300 mg/mL). RESULTS: Alloxan reduced whole pancreatic blood flow by 50%, but
      almost doubled islet blood flow. Glucose did not affect whole pancreatic blood
      flow, but increased islet blood flow 100%. Approximately 10% of the islets in
      control and glucose-injected rats contained microspheres, compared with about 25%
      in alloxan-injected rats (P < 0.001). When the islets containing a certain number
      of microspheres were compared, alloxan induced a homogeneous shift of the curve
      to the right, i.e., increased the number of islets that contained all amounts of
      microspheres. Glucose preferentially increased only the fraction of islets
      containing > or = 3 microspheres.

PMID- 8872527
TI  - Fourier-transform infrared conformational study of bovine insulin in surfactant
      solutions.
AB  - To obtain conformational data on the monomeric form of insulin, which is believed
      to be the physiologically active form of the hormone, insulin in sodium dodecyl
      sulfate solution was studied by Fourier-transform infrared (FTIR) spectroscopy
      and circular dichroism, and results were compared with those obtained with
      des(B23-30) octapeptide insulin (DOI) and dimeric insulin in buffer. The FTIR
      amide I band (1600-1700 cm-1) was examined, and a quantitative evaluation of the
      secondary structure fractions of the various conformations showed less of a beta
      sheet component for both insulin in SDS and DOI in buffer than for insulin in
      buffer, corresponding to a lack of monomers binding to form dimers. At the
      concentrations used for FTIR (> or = 2 mg/mL), the CD spectra of insulin in SDS
      and DOI in buffer were qualitatively identical but different from that of insulin
      in buffer, which is associated at these concentrations. The CD spectrum pattern
      of insulin in very dilute solution (80 nM), where it is prevalently monomeric, is
      very similar to that of monomeric insulin in SDS, which suggests that the
      conformation of the hormone in the two cases is very similar.

PMID- 8872529
TI  - Design of peptides: synthesis, crystal structure and molecular conformation of N
      Boc-L-Val-delta Phe-L-Ile-OCH3.
AB  - The dehydro-peptide Boc-L-Val-delta Phe-L-Ile-OCH3 was synthesized by the
      azlactone method in the solution phase. The peptide crystallized from a
      methanol/dimethyl sulfoxide (95:5) mixture in space group P6(1) with a = b =
      15.312(1), c = 22.164(5) A. The structure was determined by direct methods and
      refined to an R value of 0.098 for 1589 observed reflections [I > or = 1.5 sigma
      (I)]. The peptide adopts an S-shaped conformation with torsion angles: phi 1 = 
      127(1), psi 1 = -44(1), phi 2 = 67(1), psi 2 = 37(1), phi 3 = -82(1) degrees. The
      side-chain torsion angles in delta Phe of chi 2(1) = 1(2), chi 2(2,1) = 7(2) and
      chi 2(2,2) = 177(1) degrees indicate that the delta Phe residue is essentially
      planar. In valyl residue the two side-chain torsion angles are chi 1(1) = -65(1)
      and chi 1(2) = 177(1), whereas the torsion angles in Ile are chi 3(1,1) = 72(2),
      chi 3(1,2) = -159(2), chi 3(2) = 150(2) degrees. This is the first peptide which
      does not adopt a folded conformation for a sequence with a delta Phe at the (i +
      2) position. The molecular packing in the crystals is stabilized by several
      hydrogen bonds: N1-H1-...O1 = 2.77(1) A, N2-H2...O1' = 2.95(1) A, N3-H3...O2 =
      2.85(1) A and a possible weak interaction N2-H2...O2' = 3.29(1) A within the
      columns of molecules along the c-axis and van der Waals forces between the
      columns.

PMID- 8872528
TI  - Kinetic study of racemization of aspartyl residues in model peptides of alpha A
      crystallin.
AB  - We have reported that two aspartyl (Asp-151 and Asp-58) residues in alpha A
      crystallin in human eye lens were inverted to the D-isomer and isomerized to beta
      aspartyl residues with age. We report here the kinetics of the Asp racemization
      of three model peptides corresponding to fragments of alpha A-crystallin:
      IQTGLD151ATHAER (T18 peptide), TVLD58SGISEVR (T6 peptide) and HFSPED84LTVK (T10
      peptide, as a control). The rate constants of the racemization of Asp residues in
      these peptides were measured at pH 7.0, at five temperatures: 50, 60, 70, 80 and
      90 degrees C. From the Arrhenius equation, we estimated the activation energy (E)
      of racemization and the time required for the Asp D/L ratio to approximate to 1.0
      (D/L ratio of Asp = 0.99) at body temperature. For the peptide T18, E = 21.4
      kcal/mol and t = 13.5 yr. For the peptide T6, E = 26.8 kcal/mol and r = 49.5 yr.
      For the control peptide T10, E = 28.3 kcal/mol and t = 78.1 yr. The racemization
      rate of Asp in these three peptides is parallel to that of Asp residues in alpha
      A-crystallin. The racemization rate of Asp in the T18 peptide was very rapid
      compared to that in the other peptides. This result also reflects the
      racemization rate in native alpha A-crystallin.

PMID- 8872530
TI  - A convenient method for determining cyclic peptide conformation from 1D 1H-NMR
      information.
AB  - A rapid and convenient method for determining the backbone conformation of cyclic
      peptides results from the combination of 1D 1H NMR information and molecular
      modeling. phi Angle torsional constraints calculated from 3JHN.H alpha coupling
      constants are used to determine the position of multiple-welled potential energy
      penalty functions that are imposed on the force field used in the structure
      refinement (Amber* with GB/SA solvation model). Monte Carlo searches and
      minimizations lead to a collection of structures that are clustered by backbone
      similarity and then filtered according to hydrogen-bonding constraints determined
      by the chemical shift temperature dependencies of the amide protons. This
      approach was applied to five cyclic peptides whose structures had been determined
      previously using more extensive 2D NMR techniques, and the importance of the
      torsional, H-bonding, and solvation restraints were assessed. For the four
      peptides that adopt a predominant conformation, this method reproduced the
      reported structures closely; lack of convergence for the fifth structure
      reflected the multiple backbone conformations that this macrocycle adopts.

PMID- 8872531
TI  - Investigation of the 35-62 conserved helix and disulfide loop of bovine
      prothrombin using an anti-peptide antibody.
AB  - A 28-residue peptide corresponding to the 35-62 region of bovine prothrombin
      fragment 1 (BF1) was synthesized by solid-phase methods. In BF1 this region
      consists of three conserved aromatic residues within an alpha-helical region
      followed by a disulfide loop. This synthetic peptide was used to produce murine
      monoclonal antibodies (MAbs) that would recognize and bind native BF1. Antibody
      AH.Ab.E3, an IgG1 antibody that was isolated and cloned, recognized and bound to
      both the synthetic peptide and the BF1 molecule. Residues 55-59 (REKLN) were
      shown to be critical for antibody binding. This MAb was subsequently used to
      study the 48-62 disulfide loop region of BF1. MAb AH.Ab.E3, which has been shown
      to bind the BF1 calcium-dependent conformation (BF1:Ca), does not appear to
      perturb the binding interaction between BF1:Ca and phospholipid (PL) vesicles as
      studied by light scattering methods.

PMID- 8872532
TI  - New hydroxamate inhibitors of neurotensin-degrading enzymes. Synthesis and enzyme
      active-site recognition.
AB  - Selective and mixed inhibitors of the three zinc metallopeptidases that degrade
      neurotensin (NT), e.g. endopeptidase 24-16 (EC 3.4.24.16), endopeptidase 24-11
      (EC 3.4.24.11 or neutral endopeptidase, NEP) and endopeptidase 24-15 (EC
      3.4.24.15), and leucine-aminopeptidase (type IV-S), that degrades the NT-related
      peptides, Neuromedin N (NN), are of great interest. On the structural basis of
      compound JMV 390-1 (N-[3-[(hydroxyamino)carbonyl]-1-oxo-2(R)-benzylpropyl]-L-
      isoleucyl-L-leucine), which was a full inhibitor of the major NT degrading
      enzymes, several hydroxamate inhibitors corresponding to the general formula
      HONHCO-CH2-CH(CH2-C6H5)CO-X-Y-OH (with X-Y = dipeptide) have been synthesized.
      Compound 7a (X-Y = Ile-Ala) was nearly 40-times more potent in inhibiting EC 24
      16 than NEP and more than 800-times more potent than EC 24-15, with an IC50 (12
      nM) almost equivalent to that of compound JMV 390-1. Therefore, this compound is
      an interesting selective inhibitor of EC 24-16, and should be an interesting
      probe to explore the physiological involvement of EC 24-16 in the metabolism of
      neurotensin.

PMID- 8872533
TI  - Dissociation, unfolding and inactivation of creatine kinase in urea solutions.
AB  - It was previously reported that, during unfolding of creatine kinase in
      guanidinium chloride or urea solutions, inactivation occurred before noticeable
      conformational change could be detected, suggesting that the conformation at the
      active site is more easily perturbed and, hence, more flexible than the molecule
      as a whole [Tsou (1986) Trends Biochem. Sci 11, 427-429]. In the present paper,
      the ureagradient electrophoresis and the isoenzyme hybrid of creatine kinase has
      been studied. The results show that at low urea concentrations, creatine kinase
      is still in the dimeric state or only slightly dissociated. The dissociation and
      inactivation of creatine kinase during denaturation by urea are also compared. It
      was found that the enzyme was nearly inactivated in low urea concentrations
      before noticeable dissociation was detected. It therefore appears that in low
      urea concentrations, inactivation of creatine kinase is not due to the
      dissociation of the active dimer. The present result supports the hypothesis of
      the conformational flexibility of the active site in this enzyme.

PMID- 8872534
TI  - Synthesis of lipidic amino acid and dipeptide inhibitors of human platelet
      phospholipase A2.
AB  - Phospholipases A2 (PLA2s) catalyze the hydrolysis of glycerophospholipids at the
      sn-2 position, and their inhibition is considered a rational approach for the
      prevention and treatment of inflammation. A number of amides and esters of alpha
      amino acids with saturated linear side chains, esters of alpha-amino alcohols and
      derivatives of lipidic peptides were prepared and tested against secreted humal
      platelet phospholipase A2. Among the compounds tested the amides of free amino
      acids with long-chain amines presented the highest in vitro inhibitory activity.

PMID- 8872535
TI  - Structure-activity studies on C-terminal hirudin peptides containing sulfated
      tyrosine residues.
AB  - To clarify the role of the negative charge of the C-terminal region of hirudin,
      we chemically synthesized the C-terminal peptide of hirudin variant-1 (HV-1), HV
      1-(54-65), and its analogs, [E61Y,E62Y]HV-1-(54-65) and [E62Y]HV-1-(54-65), and
      then sulfated the Tyr residue(s) in these peptides by both enzymic and chemical
      methods. Enzymic O-sulfation of Tyr residues in the peptides by use of
      sulfotransferase isolated from Eubacterium A-44 allowed us to produce four kinds
      of the sulfated peptide, whose C-terminal sequences were -PEY(SO3H)YLQ, 
      PYY(SO3H)YLQ, -PYYY(SO3H)LQ and -PYY(SO3H)Y(SO3H)LQ. On the other hand, all Tyr
      residues in the peptides were successfully sulfated by chemical reaction with
      N,N'-dicyclohexylcarbodiimide in the presence of sulfuric acid. Based on the
      analysis of structure-activity relationships of these sulfated peptides for
      thrombin inhibition, the Tyr62 and Tyr63 bisulfated peptide
      GDFEEIPEY(SO3H)Y(SO3H)LQ was found to be the most potent inhibitor of thrombin
      among the products tested. No increase in potency was observed by further
      substitution of Glu61 with Tyr(SO3H). The inhibitory activity by substitution
      with Tyr(SO3H) at position 63 was greater than that obtained by the substitution
      at position 62.

PMID- 8872536
TI  - Purification and characterization of ostrich pancreatic secretory trypsin
      inhibitor.
AB  - Ostrich pancreatic secretory trypsin inhibitor was isolated and purified using
      acid extraction, salt fractionation. SP-Sephadex C-50 and QAE-Sephadex A-25
      chromatography and RP-HPLC. The amino acid sequence of ostrich PSTI showed it is
      a single peptide chain containing 69 amino acid residues with the highest
      homology between ostrich and chicken PSTI. The molecular weight, as determined by
      electronspray mass spectrometry and from amino acid sequence data, is 7650 Da.
      The isoelectric point of ostrich PSTI was found to be 5.7. Ostrich PSTI
      specifically inhibited ostrich and commercial bovine trypsin with Ki values of
      8.0 x 10(-9) and 2.4 x 10(-7) M, respectively, while no inhibitory effects were
      observed with other serine proteases.

PMID- 8872537
TI  - Synthesis of peptide p-nitroanilides mimicking fibrinogen- and hirudin-binding to
      thrombin. Design of slow reacting thrombin substrates.
AB  - The design and synthesis of 20 peptide p-nitroanilides is described. The
      nitroanilides are used as thrombin substrates that share uncommon properties.
      These substrates are tested for their applicability to measure thrombin
      generation in activated plasma. This technique requires substrates that must
      slowly but selectively be hydrolyzed by thrombin. To ensure selectivity,
      thrombin's natural substrate and its most potent inhibitor were used as lead
      compounds. Eighteen peptide p-nitroanilides were synthesized using human
      fibrinogen A alpha [7-16] decapeptide as lead structure since this fragment
      constitutes the minimal sequence which binds to thrombin with high affinity. Two
      other chromogenic substrates were designed using 5-amino-2-nitrobenzoic acid as
      the chromophore. A peptide giving subsite interactions with the fibrinogen
      recognition exosite was coupled to the carboxylic function. As the peptide
      segment, the carboxyl terminal part of hirudin (residues 50-65) was chosen to
      ensure highly specific thrombin recognition. From the 20 nitroanilides
      synthesized, we indeed obtained a number of compounds which can be used as
      substrate in the thrombin generation assay.

PMID- 8872538
TI  - Synthesis and biological evaluation of an iodinated iberiotoxin analogue, [mono
      iodo-Tyr5, Phe36]-iberiotoxin.
AB  - The synthesis and iodination of a structural analogue of the specific large
      conductance calcium-activated potassium (BK) channel blocker, iberiotoxin (IbTX),
      a 37-amino acid scorpion neurotoxin, is reported. The synthesis of this analogue,
      [Tyr5, Phe36]-IbTX, was accomplished using standard solid-phase Fmoc (9
      fluorenylmethoxycarbonyl) chemistry protocols. The linear peptide was cyclized
      via the formation of three intramolecular disulfide bridges and subsequently
      iodinated at the Tyr5 position. Upon purification, the iodinated analogue, [mono
      iodo-Tyr5, Phe36]-IbTX, exhibited comparable biological activity to native IbTX
      in blocking BK-mediated currents. These findings suggest the synthesis and use of
      an 125I labelled IbTX analogue for BK channel localization in autoradiography
      experiments.

PMID- 8872539
TI  - Synthesis of phospho-urodilatin by combination of global phosphorylation with the
      segment coupling approach.
AB  - The chemical synthesis of biologically active phosphorylated urodilatin (CDD/ANP
      95-126) was achieved by using a strategy of coupling protected peptide segments
      in solution. Three protected peptide segments corresponding to urodilatin (1-14)
      with side chain-unprotected Ser10, (15-24) and (25-32) were prepared manually
      using Fmoc chemistry on an aminopropyl polystyrene resin with the super acid
      labile HMPB linker. For the coupling of segments, the carboxy group of the C
      terminal segment (25-32) was converted into the tert-butyl ester by treatment
      with TBTA. The protected peptide segments were coupled in the presence of
      EDC/HOOBt or TBTU/HOBt to yield fully protected urodilatin with a free hydroxy
      function at Ser10. Introduction of the phosphate was performed with Et2NP(OtBu)2
      and tetrazole followed by oxidation of the phosphite. Alternatively, a
      prephosphorylated protected segment (1-14) was used in the segment condensation.
      Our investigations indicate that both pathways, phosphorylation of protected
      urodilatin in solution and use of a prephosphorylated building block, are
      suitable methods to obtain a large phosphopeptide of high purity without
      formation of H-phosphonates or other by-products.

PMID- 8872540
TI  - Antibiotic-associated colitis in orthopaedic patients.
AB  - Antibiotic-associated colitis was diagnosed in 23 orthopaedic patients: 17 had
      abdominal symptoms, 3 had a fever and the remaining 3 had no symptoms but
      increasing C-reactive protein values or white blood count. The antibiotic was
      clindamycin in 19, cephalosporins in 3 and a combination of vancomycin and
      fusidic acid intravenously in one. The antibiotics were stopped in 12, changed in
      5 and continued in the remaining 5. Oral treatment for colitis was given in 21
      patients, and in one patient the only treatment was stopping the antibiotics. One
      patient died after a myocardial infarct; the remaining 22 were discharged after
      successful treatment of their primary condition and the colitis.

PMID- 8872541
TI  - Treatment of frozen shoulder by distension and manipulation under local
      anaesthesia.
AB  - We report the results of hydraulic distension of the glenohumeral joint with
      manipulation using local anaesthesia and radiographic control in 24 frozen
      shoulders in 22 patients. In a prospective study, the pre- and postoperative
      range of movement in 3 planes was measured by an electronic digital inclinometer.
      At 3 months, the range compared with the unaffected shoulder was abduction 93%,
      glenohumeral abduction 84%, forward flexion 94%, backward extension 96%, internal
      rotation 75% and external rotation 73%. The procedure was repeated once in 3
      patients. One also had a manipulation under general anaesthesia and was classed
      as a failure. The subjective outcome was good in all the other patients. This
      investigation shows that the technique is safe, reliable and effective treatment
      for frozen shoulder.

PMID- 8872542
TI  - Simplification of the Elmslie-Trillat procedure for patellofemoral malalignment.
      Is medial capsulorraphy necessary?
AB  - We describe a modification of the Elmslie-Trillat operation which includes a
      lateral retinacular release and medial realignment of the tibial tuberosity, but
      omits medial capsulorraphy. Seventy-five patients were reviewed with a follow up
      longer than 2 years and the results compared with the conventional Elmslie
      Trillat procedure, which consists of lateral release, medial realignment of the
      tuberosity and medial capsulorraphy. The simpler operation can work as well and
      the period of rehabilitation is shorter. The incidence of injury to the saphenous
      nerve is reduced and the cosmetic appearance is more satisfactory. We conclude
      that medial capsulorraphy is usually unnecessary in this type of procedure.

PMID- 8872543
TI  - Determination of periprosthetic bone density with the DEXA method after
      implantation of custom-made uncemented femoral stems.
AB  - Implantation of a total hip replacement leads to resorption of bone, especially
      in the upper femoral shaft and this depends mainly on the design of the stem, and
      also on the survival time of the implant. Density of the periprosthetic bone was
      examined with the DEXA method in both femurs in 27 patients at a mean of 21
      months after implantation of uncemented custom-made femoral stems. A loss of bone
      density between 5% and 21% was found which was independent of the survival time
      of the implant. The maximum decrease was at the upper medial part of the calcar.
      The negligible loss of bone density, compared to other reports, favours the use
      of a computer tomography assisted custom-made femoral stem.

PMID- 8872544
TI  - Bipolar hip replacement in sickle cell disease.
AB  - A retrospective study is presented of 26 uncemented bipolar hip replacements for
      avascular necrosis of the femoral head due to sickle cell disease which were
      carried out between 1987 and 1992. All patients were treated according to a
      protocol. The average follow up was 4.6 years (range 2.1 to 7 years). After
      operation, the average Harris hip score improved from 36 to 88. Bone culture was
      positive for bacterial growth in 4 hips (coagulase negative staphylococcus in 3).
      There was progressive wear of acetabular articular cartilage in 2 cases, but no
      clinical or radiological evidence of loosening of the femoral stem. Seventeen
      complications occurred in 9 of the 21 patients (5 in one patient). A longitudinal
      split of the femur was the commonest operative complication and occurred in 5
      hips. Femoral medullary sclerosis was seen in 8 cases. Patients with sickle cell
      disease have a high risk of complications, but this type of hip replacement
      should be considered in carefully selected patients who have avascular necrosis
      of the femoral head.

PMID- 8872545
TI  - Polyostotic fibrous dysplasia. A long-term follow up of 8 patients.
AB  - Eight patients who had polyostotic fibrous dysplasia were followed up for more
      than 10 years. One had the Albright syndrome. Two of 3 proximal femoral lesions
      which were treated before puberty by either curettage and bone grafting or by
      osteotomy, developed progressive deformity during the growth period. One of 2
      proximal femoral lesions treated by curettage and bone grafting after the age of
      18 also developed a deformity. Two tibial lesions operated on at the age of one
      and 30 years remained stable. The histological findings showed more active
      lesions in young patients compared with adults.

PMID- 8872546
TI  - Adjuvant local treatment of parosteal osteosarcoma.
AB  - Four patients with parosteal osteosarcoma of the distal femur were treated by
      resection and insertion of cement. The resection was marginal in 3 patients and
      intralesional in one. The histology was grade 1 in 3 and grade 2 in one. The
      cement was subsequently removed and a fibular autograft used for reconstruction.
      The average follow up was 88 months (range 20 to 161 months). The function of the
      affected limb was excellent. The best time to remove the cement was after one
      year.

PMID- 8872547
TI  - Fracture of the shaft of the humerus with a fracture-dislocation of the same
      shoulder. A case report.
AB  - We report the case of a man aged 19 who sustained an anterior dislocation of the
      shoulder with a fracture of the greater tuberosity, and a fracture of the shaft
      of the same humerus. Open reduction and internal fixation of the shaft fracture
      was carried out followed by closed manipulation of the dislocation. He recovered
      full function of the shoulder and elbow.

PMID- 8872548
TI  - Orthopaedic biomechanics. The past, present and future.

PMID- 8872549
TI  - Osteosynthesis in trauma.

PMID- 8872550
TI  - Orthopaedic surgery and HIV disease in Africa.
AB  - Human immunodeficiency virus (HIV) infection has radically changed African
      orthopaedic practice within a decade. In Lusaka, a third of adults are infected,
      but most have no physical signs of the disease. Early experience showed that
      closed fractures healed normally, the risk of sepsis during osteosynthesis was
      increased and most open fractures became septic. Major orthopaedic surgery in HIV
      positive patients has increased risks of sepsis which rise steeply in those with
      physical signs of HIV disease. Musculoskeletal infections such as tropical
      pyomyositis, adult haematogenous long-bone osteomyelitis, and late haematogenous
      infection of implants, appear as immune competence wanes. There is a dual
      epidemic of tuberculosis and HIV, and bone and joint tuberculosis is now common.
      Atypical features suggest that traditional diagnostic criteria for spinal
      tuberculosis may be inadequate. Rheumatoid diseases, especially reactive
      arthritis, are common and serious complications of HIV disease. The risk of
      transmission of HIV between patient and surgeon is small, especially if
      recommended precautions are universally applied.

PMID- 8872551
TI  - Partial-thickness tears of the rotator cuff. A clinicopathological review based
      on 66 surgically verified cases.
AB  - This review is based on 66 patients with partial-thickness tears of the rotator
      cuff, verified at operation. Their average age was 54 years, and all had symptoms
      of subacromial impingement. The duration of shoulder pain was for between 2 and
      108 months (mean 11.4 months). Ultrasonography, arthrography and bursography were
      helpful in establishing the diagnosis. On exploration, tears were found in the
      supraspinatus tendon, with 9 extending into the infraspinatus. After anterior
      acromioplasty, excision of the diseased portion and tenorrhaphy were undertaken.
      Satisfactory results were obtained in 62 patients (94%) with an average follow-up
      of 32 months. Spontaneous repair at the torn site was never seen. In addition to
      Neer's staging of impingement, we propose a new classification based on the
      integrity of the cuff tendon. We conclude that a partial-thickness cuff tear is
      an important cause of shoulder disability, which deserves much more clinical
      attention; misdiagnosis is common and leads to mismanagement. When conservative
      treatment fails, accurate diagnosis and proper surgical repair are essential.

PMID- 8872552
TI  - Knee ligament injuries. Pathoanatomy, biomechanics, instabilities and
      possibilities of treatment in acute and chronic injuries.

PMID- 8872553
TI  - Severe kyphotic deformity in tuberculosis of the spine.

PMID- 8872554
TI  - Comparative electronmicroscopical investigations on the influences of altered
      gravity on cytochrome oxidase in the inner ear of fish: a spaceflight study.
AB  - The regional metabolic activity in the otolithic sensory epithelia of the inner
      ear of a cichlid fish (Oreochromis mossambicus) was investigated on light- and
      electronmicroscopical level using the cytochemical method for detection of
      cytochrome oxidase activity. In adult animals a characteristic distribution of
      mitochondria with high enzyme activity was found in sensory and non-sensory cells
      of otolithic sensory epithelia, which was correlated with regions with a high
      energy demand. These findings were the basis for studies on the influence of long
      term altered gravity conditions in developing larvae: hypogravity (10(-4) g in
      spaceflight), normal gravity (1 g in a centrifuge in space and 1 g on earth) and
      hypergravity (3 g in a laboratory centrifuge). Cytochrome oxidase activity was
      quantified in different parts of the sensory hair cell synapse in the vestibular
      sensory epithelia utricle and saccule: apical and basal cytoplasm, postsynaptic
      area of the afferent synapse and presynaptic region of the efferent synapse. Our
      results show that the energy metabolism of utricle, but not of saccule is
      decreased after microgravity exposure during the 2nd German Spacelab Mission D-2.
      However, a general effect of the spaceflight is detectable in both sensory
      epithelia. Long-term exposure to increased acceleration (3 g) had no effects on
      cytochrome oxidase activity in inner ear sensory epithelia.

PMID- 8872555
TI  - Autoradiographic and electron microscopic studies of retinal rosettes in
      genetically microphthalmic mice.
AB  - We report results obtained in the microphthalmic strain of mice 944.
      Heterozygotes appear normal, but they produce litters in which typically between
      2 and 5 offspring exhibit microphthalmia and rosettes in the retina and the optic
      nerve. As a result these animals are blind. Our investigations using 3H-thymidine
      for autoradiographic estimation of postnatal cell proliferation and electron
      microscopy for detailed observation of the morphology of the rosettes show an
      increased proliferation of neuronal cells (more than 200%), especially in
      rosettes. In the rosettes a centrally located lumen exists in which cytoplasmatic
      processes can be found. In ultrastructural investigations these processes were
      identified as residues of the outer segments of photoreceptor cells.

PMID- 8872556
TI  - The effects of nerve growth factor on newborn rat dorsal root ganglion neurons in
      vitro: a scanning electron microscopic observation.
AB  - The effects of nerve growth factor (NGF) on the three-dimensional structure of
      newborn rat dorsal root ganglion (DRG) neurons, in vitro, were examined by
      scanning electron microscopy. Throughout the culture in both NGF treated and
      control groups, two types of structures of the surface were recognized, smooth
      surfaced and rough surfaced neurons. Growth cones and varicosities of the
      processes were observed after 12 hours of culture in NGF-treated groups, in
      contrast they were observed after 24 hours in control groups. The size and number
      of growth cone and varicosity was greater in NGF-treated groups than in control
      groups. NGF elongated the processes of DRG neurons after 24 hours of culture. NGF
      also significantly increased the number of surviving neurons after 48-72 hours of
      culture. Rough surfaced neurons were more sensitive than smooth surfaced neurons
      to NGF in enhancing survival. These results suggest that NGF may induce
      maturation of DRG neurons through elongation of its processes and the formation
      of growth cones and varicosities. Furthermore, the perikaryal projections of DRG
      neurons may be related to neuron survival after NGF treatment.

PMID- 8872557
TI  - Noradrenergic and dopaminergic systems in the central nervous system of the
      hedgehog (Erinaceus europaeus).
AB  - The distribution of the noradrenaline (NA)- and dopamine (DA)-containing neuronal
      structures in the central nervous system of the hedgehog (Erinaceus europaeus), a
      phylogenetically old mammalian species, was immunocytochemically studied
      employing antibodies directed against the catecholamines (CA) themselves. Groups
      of DA cell bodies observed in this study were similar to those present in other
      species but the distributional map of the NA-containing cell bodies exhibited
      some peculiarities. Prominent among them were the absence of the A3 group and the
      paucity of CA cells in the A2 group. DA neurons in the hypothalamus, apart from
      the densely populated paraventricular and arcuate nuclei, were fewer and less
      widely distributed than in other species. In the hedgehog mesencepha- Ion, in
      contrast to what has been described in other species, the major DA cell group was
      present in the ventral tegmental area. CA immunoreactive fibers were widely
      distributed in the CNS of the hedgehog. However, similarly to what has been
      observed in other species, terminal fields of DA neurons were much more
      restricted when compared to those of the NA neurons. The neocortical DA
      projection system of the hedgehog appeared less developed but organized similar
      to that of the rat, and even less developed than that of the primates. The lack
      of profound regional and laminar variations in the density of cortical NA fibers
      in the hedgehog enhances the suggestion that the elaboration and differentiation
      of the NA cortical system parallels the phylogenetic development of the cortex.
      In the brainstem, interspecies differences in the distribution of the CA fibers
      were found to concern primarily some hypothalamic areas (medial preoptic area,
      suprachiasmatic nucleus, arcuate nucleus). Such differences in the thalamus
      concerned the NA innervation and they were notably present in the visual thalamic
      nuclei (dorsal lateral geniculate nucleus, lateral posterior thalamic nucleus).
      In the spinal cord, which was found to receive fewer CA afferents than those
      found in other species, the density of the DA fibers was much lower than that of
      the NA axons. In addition to the CNS areas that have been described in other
      species to receive catecholaminergic innervation, the present study showed that
      both types of catecholaminergic fibers are distributed in the choroid plexus and
      along the ventricular wall of the brain ventricles and the central canal of the
      hedgehog.

PMID- 8872558
TI  - Distribution patterns of Wisteria floribunda agglutinin binding sites and
      parvalbumin-immunoreactive neurons in the human visual cortex: a double-labelling
      study.
AB  - Extracellular lattic-like coatings--known as perineuronal nets (PNs)--ensheath
      certain types of neurons in the mammalian neocortex. PNs and densely stippled
      zones in some cortical layers contain proteoglycans stainable e.g. with several
      plant lectins. The present study is focused on the binding sites of the plant
      lectin Wisteria floribunda agglutinin (WFA) and on its relationship to
      parvalbumin-immunoreactive (PARV-ir) neuronal constituents in the human visual
      cortical fields 17 and 18. Size and numbers of PNs varied not only between these
      two areas, but also between its layers. In area 17 the PNs appeared accumulated
      in two conspicuous bands which included layer IV, particularly layer IVb, and
      layer VI. Layer IVc of area 17 contained numerous small faintly stained PNs. In
      area 18 a two-tiered organization of PNs in layers IIIb-c and layer V was
      emphasized. The neuropil staining by WFA was much more intense in layers IIIb-c
      of area 18 than of area 17. In areas 17 and 18 the vast majority of PNs was
      associated with sub-populations of PARV-ir cells resembling several classes of
      GABAergic cortical interneurons. Among PARV-negative cells surrounded by PNs,
      only exceptionally pyramide-like neurons were detected. The patterns of lectin
      labelling in the human visual primary and association cortex resembled those of
      macaque monkeys and differed from those in the visual cortex of rat and gerbil.
      These differences between mammals representing divergent modes of visual
      specialization may support the view that such extracellular matrix components in
      these occipital cortical areas are involved in visual information processing
      subserving fast inhibitory interneuronal actions.

PMID- 8872559
TI  - Corticospinal collaterals to medullary cardiovascular nuclei in the rat: an
      anterograde and a retrograde double-labeling study.
AB  - There is little evidence allowing the hypothesis of the existence of direct
      pathways from the sensorimotor cortex (SMC) to main cardiovascular medullary
      nuclei: the dorsal motor nucleus of the vagus (DMV), the nucleus of the solitary
      tract (NTS) and the rostral ventrolateral medulla (RVLM). The purpose of this
      study was to identify in the rat direct SMC-NTS/DMV and-RVLM projections
      descending through the pyramidal tract (PT) and corticospinal neurones projecting
      to spinal somatic centers and sending collaterals to the NTS/DMV and the RVLM.
      The first group of animals (N = 15) received injections of anterograde tracers
      into the SMC: wheat germ agglutinin conjugated to horseradish peroxydase (WGA
      HRP) or rhodamine-conjugated dextran (DR). In the second group (n = 35),
      retrograde tracers were injected: fluorogold (FG) into the NTS/DMV or into the
      RVLM and DR into the lateral thoracic cord (Th2-Th4). Anterograde transport of
      WGA-HRP and DR allowed corticofugal fibers to be followed inside the PT
      ipsilaterally to the site of cortical injection and showed bilateral labeled
      projections to the NTS/DMV and RVLM. After retrograde transport, bilateral FG or
      DR labeled cells were distributed in the SMC, mainly in the medial (AGm) and
      lateral (AGl) agranular cortex. After spinal and bulbar injections, double
      labeled cells were distributed in same cortical areas. After injections in RVLM,
      49% of labeled cells showed a double-labeling in the frontal cortex (rostral AGm
      and premotor cortex) while only 24% were observed in the posterior SMC (caudal
      AGl). On the contrary, when injections were done in NTS/DMV, double-labeled
      neurons were respectively of 11% in the frontal cortex and 4% in the posterior
      SMC. In the present work it was shown that the SMC sent direct projections to
      bulbar cardiovascular nuclei by means of fibers descending through the PT and
      corticospinal collaterals. The hypothesis which may be drawn from this study is
      that cortical motor areas probably program cardiovascular adjustments,
      preparatory or concomitant to the control of striate muscles.

PMID- 8872560
TI  - Neuroprotective effects of thiamine-megadoses after long-term ethanol application
      in the rat brain. A structural investigation of hippocampal CA1 pyramidal and
      cerebellar Purkinje neurons.
AB  - Using the Golgi-impregnation technique we could document that twenty weeks of
      ethanol consumption induce significant elongation of dendritic spines of rat
      cerebellar Purkinje cells, and as demonstrated for the first time in the present
      study, of hippocampal pyramidal neurons. Spine hypertrophy might be the result of
      compensative growth of spines in search of new synaptic contacts due to neuronal
      cell loss caused by the prolonged ethanol intake. In contrast, this
      neuromorphological alteration could not be detected in the alcohol group fed at
      the same time with a high dose of thiamine (119 mg/100 g food) =
      thiaminemegadose). As thiamine participates in a number of enzymatic reactions
      primarily concerned with carbohydrate metabolism, it may be concluded that
      megadoses of thiamine are able to support neuronal energy metabolism, which was
      initially impaired by ethanol-induced thiamine deficiency. Therefore, a
      megavitamintherapy in association with chronic alcohol intake could be able to
      attenuate or prevent ethanol-induced damages in rat central nervous system.

PMID- 8872561
TI  - c-fos expression in the parabrachial nucleus following cardiovascular and blood
      volume changes.
AB  - c-fos expression was analyzed by means of Fos-immunocytochemistry in the
      parabrachial (PB) nucleus of rats anesthetized and submitted to blood pressure or
      volume changes. The objective was to determine if neurons of the PB are
      differentially activated following increase or decrease of arterial pressure or
      blood volume. Hypertension or hypotension were induced by continuous intravenous
      infusion of phenylephrine hydrochloride or sodium nitroprusside, respectively.
      Changes in blood volume were induced by volume load caused by infusion of
      isotonic saline or hemorrhage. Both an increase and a decrease in blood pressure
      resulted in elevated levels of Fos-IR neurons in the central lateral, dorsal
      lateral, and external lateral (outer section) subnuclei of the PB. No Fos-IR
      cells were observed in the external medial, internal lateral and ventral lateral
      PB. Only occasionally we could see few Fos-immunoreactive (Fos-IR) neurons in the
      medial and superior lateral PB subnuclei. A very similar pattern of c-fos
      expression was seen after volume load or hemorrhage. Our results demonstrate that
      blood pressure or volume changes elicit c-fos expression in specific and
      apparently identical sets of neuron populations in the parabrachial nucleus. We
      conclude that these neurons, which seem to receive a stimulatory drive, are
      involved in the central neural control of both cardiovascular and blood volume
      regulation.

PMID- 8872562
TI  - A quantitative study of the effects of microphthalmia on the organisation of the
      primary visual system of the mouse.
AB  - The retinal projections of C57BL/Orl mice homozygous for the mutation
      microphthalmic-white (Miwh) were investigated by autoradiographic and HRP tracing
      techniques, and compared to those of heterozygous and normal mice of the same
      inbred strain; the anatomy of the eyes and optic nerves of the three genotypes
      were also examined. The eye of homozygous mutant mice is considerably reduced in
      size; the optic nerve shows a decrease in the number of myelinated fibres which
      is partially compensated by an increase in the proportion of unmyelinated axons.
      All primary visual centres that are labelled in normal mice receive retinal
      projections in mutant mice, although these centres are reduced in size in
      mutants. The reduction is most evident for those centres forming the thalamic
      relays of the retino-telencephalic pathway, to a lesser extent for the retino
      collicular pathway and least of all for the retino-hypothalamic projections.
      These findings are compared to those obtained in naturally microphthalmic rodent
      species, and also to the effects of another mutation at the mi locus, maintained
      on a different background.

PMID- 8872563
TI  - Calretinin immunoreactivity in the monkey and cat cerebellum: cellular
      localisation and modular distribution.
AB  - We have studied the morphology and distribution of calretinin-containing neurons
      in the cat and monkey cerebellum immunocytochemically. Immunoreactivity is
      detectable in cortex and white matter, with cell bodies mainly in the granular
      layer, the commonest of which are granule cells. Labelled Lugaro cells and a type
      of bipolar neuron are also occasionally seen. Other larger cells in the granular
      layer are strongly labelled. They are characterised by a spherical cell body
      giving rise to a thick primary dendrite with a spray of terminal appendages, like
      the unipolar brush cells (UBC) described in several species. They are distributed
      according to a mediolateral gradient of numerical density, with most in
      parasagittally congruent cell clusters in the vermis and the paravermal parts of
      the hemispheres. The axons of UBCs originate from the soma or primary dendrite,
      and are a major source of labelled fibres in the granular layer. Positively
      stained climbing fibres are radially oriented in the white matter and cortex, and
      form longitudinal bands, especially in the vermis. Climbing fibre bands are
      congruent with UBC clusters in the vermis but less so in the hemispheres. Both
      mossy and climbing fibres seem likely to synapse on UBSs. We postulate that a
      pathway from afferent fibres to UBCs to Purkinje cells may represent a short
      circuit for rapid cerebellar reflexes without passing through much of the
      multisynaptic circuits of the cortex. Calretinin may be involved in signal
      processing in the cerebellum, perhaps regulating the amount and form of
      intracellular calcium.

PMID- 8872564
TI  - An atlas of the distribution of NADPH-diaphorase in the brain of the highly
      derived swordtail fish Xiphophorus helleri (Atherinoformes:Teleostei).
AB  - The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (or 
      dehydrogenase, NADPHDH, a marker for nitric oxide synthase, NOS) positive neurons
      was demonstrated histochemically in the central nervous system of the swordtail
      fish Xiphophorus helleri, a highly derived telost of the atherinomorph outgroup.
      All nuclei of the swordtail fish, comprising almost all nuclei that have been
      described so far regarding the brains of telosts in general, were investigated.
      The results obtained clearly indicate, that NADPHDH positive neurons in the
      swordtail fish mostly are restricted to evolutionary primitive brain areas such
      as to most dorsomedial, dorsocentral and ventral portions of the telencephalon,
      to the preoptic area and to some thalamic, hypothalamic and pretectal nuclei of
      the diencephalon including the pituitary and the pineal organ, to the nuclei of
      the mesencephalic and myelencephalic cranial nerves, to the myelencephalic
      reticular formation and to the Mauthner cells. Some positive neurons were also
      observed within the mesencephalon, including the cerebellar body and its valve.
      Among non-neuronal cells, especially ependymocytes were strongly stained. It is
      the particular goal of the present study to provide a complete account on NADPHDH
      in the brain of a fish species, since, firstly, the NADPHDH/NOS system becomes
      increasingly important with regard to the understanding of the molecular basis of
      memory formation, and, secondly, fishes generally are more and more intensively
      studied concerning neurobiological approaches.

PMID- 8872565
TI  - Cemented revision total hip arthroplasties in patients younger than 55 years old.
      A multicenter evaluation of second-generation cementing technique.
AB  - The results of all cemented first-time revisions in Sweden performed in patients
      younger than 55 years of age, during the period 1984-1986, are reported. The
      revisions were performed by the average orthopaedic surgeon in 25 hospitals
      distributed throughout Sweden. Second-generation femoral cementing technique was
      used. One third of the acetabular revisions were performed with pressurized
      cement. The reason for revision was aseptic loosening. Seventy hips in 68
      patients were reviewed at an average follow-up period of 7 years (range, 4-10
      years). The average age of the patients at the time of revision surgery was 47
      years. Forty-eight cups and 57 stems were revised using cement. Survival
      analysis, with revision for aseptic loosening as the endpoint, suggests an
      overall 76% survival rate after 8 years. The survival rate for the cup was 80%,
      and for the stem, 85%. The radiographic evaluation revealed that the cement
      mantle was inadequate in many revisions. Localized osteolysis was rare. Clinical
      data were reported for 55 (53 patients) non-revised hips. Thirty-five hips were
      without pain or slightly painful. Forty patients limped when walking. Forty-three
      patients were satisfied with the revised hip. These results using second
      generation femoral cementing technique are better than those reported with first
      generation technique, but the failure rate in this young patient population is
      too high. The search for a more durable fixation in revision total hip
      athroplasty for young patients with long life expectancy is ongoing. These
      results emphasize that there is a need for centralization to gain experience in
      extended clinical research and to further improve surgical and cementing
      techniques.

PMID- 8872566
TI  - Impacted particulate allograft for femoral revision total hip arthroplasty. In
      vitro mechanical stability and effects of cement pressurization.
AB  - The initial migration and micromotion of the revision femoral stem stabilized
      with morselized impacted cancellous allograft and bone-cement and the influence
      of cement pressurization on fixation of the cement/allograft composite to the
      host were examined with human cadaver femurs. The stability of the
      allograft/cemented reconstruction was found to be intermediate between those of
      conventional cemented and cementless stems. In most cases, the stability of the
      reconstruction was closer to that of cemented than to that of cementless stems.
      This may account for histologic findings of graft incorporation in experimental
      and retrieved specimens reported by other authors. Although increased cement
      pressurization led to greater penetration of cement into the graft bed, greater
      cement penetration did not increase fixation strength of the cement/allograft
      composite to the host.

PMID- 8872567
TI  - Patellar tilt and subluxation following subvastus and parapatellar approach in
      total knee arthroplasty. Implication for surgical technique.
AB  - Eighty-nine posterior-stabilized total knee arthroplasties (TKAs) were studied
      using a Merchant view to assess patellar tilt or subluxation. Forty TKAs were
      performed via the subvastus approach (SVA) and 49 via the standard parapatellar
      approach (PPA). Intraoperative tracking was assessed using a "no thumbs" test,
      and a lateral release was performed if necessary. Following the SVA, 40.0% of
      patellas tracked centrally compared to 44.9% for the PPA. With the SVA, a lateral
      release was necessary in 27.5% of procedures compared to 51.0% for the PPA. The
      data suggest that the no thumbs test may overestimate the need for lateral
      release following the PPA. Since there are fewer lateral releases following the
      SVA, reapproximation of the medial retinaculum to assess intraoperative tracking
      may result in fewer lateral release being performed without adversely affecting
      patellar position. Medial tilting of the patella is also found to be common;
      29.7% of the patellas tilted this way, including 40.0% of knees operated via the
      SVA. Why this occurs is unclear, but the incidence of medial tilting increased
      after posterior-stabilized TKA.

PMID- 8872568
TI  - Soft tissue expansion prior to arthroplasty in the multiply-operated knee. A new
      method of preventing catastrophic skin problems.
AB  - Ten knees in nine patients underwent gradual soft tissue expansion prior to major
      knee surgery. All patients had multiple prior operative procedures around the
      knee. The resultant multiple skin incisions were felt to potentially jeopardize
      the postoperative status of the soft tissues. Each knee underwent the surgical
      placement of a tissue expander through a bed of adjacent healthy soft tissue
      followed by the gradual inflation of the expander over an average of 64.5 days.
      The average volume of soft tissue expansion was 313.7 mL per knee. Subsequent
      major knee surgery requiring an arthrotomy was performed at the time of expander
      removal followed by uncomplicated soft tissue closure. All wounds healed without
      any complications.

PMID- 8872569
TI  - Treatment of early symptomatic pulmonary embolism after total joint arthroplasty.
AB  - The purpose of this study was to evaluate the risk of intravenous heparin therapy
      or the use of Greenfield filters (Meditech, Watertown, MA) in the early
      postoperative period in patients who have documented symptomatic pulmonary
      embolism. Symptomatic pulmonary embolism in the first weeks was identified in 52
      patients. Twenty-four patients were treated with Greenfield filter insertion and
      28 patients with intravenous heparin therapy. One complication associated with
      insertion of the Greenfield filter-premature opening in the internal jugular vein
      resulted in no adverse consequences. Three complications were associated with
      intravenous heparin therapy: one transient thrombocytopenia, one recurrent
      symptomatic pulmonary embolism, and one knee hematoma, which did not require
      surgical evacuation. It appears that Greenfield filter insertion is a viable
      option for treatment of symptomatic pulmonary embolism in the early postoperative
      period after total joint arthroplasty. In contrast to other published data, this
      study suggests that intravenous heparin therapy may also be a reasonable
      alternative, but is a treatment regimen that requires careful monitoring of
      platelets, wound complications, and bleeding parameters.

PMID- 8872570
TI  - Poor reproducibility in radiographic grading of femoral cementing technique in
      total hip arthroplasty.
AB  - The first study of the reproducibility of a widely accepted grading system for
      femoral cementation in total hip arthroplasty is reported. Sixty postoperative
      radiographs were graded on two occasions at least 2 weeks apart by two
      experienced observers. The test-retest reproducibility rate was 60% for observer
      1 and 70% for observer 2. The interobserver reproducibility varied between 60 and
      63% for the different assessments. Between 5 and 6% of cases differed by more
      than one grade between tests. Kappa statistical analysis confirmed that
      reproducibility was poor in all cases. This cement grading system, even in the
      hands of experienced observers, has too high a rate of intraobserver and
      interobserver error to recommend its use.

PMID- 8872571
TI  - Does total hip arthroplasty predispose to chronic venous insufficiency?
AB  - One hundred thirty-four limbs (40% retrieval) were reviewed 14 to 21 years after
      total hip arthroplasty. Each had been screened for deep vein thrombosis following
      surgery by the fibrinogen uptake test, with proximal thrombi confirmed
      venographically. The limbs were assessed for chronic venous insufficiency with a
      standard clinical grade and photoplethysmography. Clinical chronic venous
      insufficiency was found in 4 of 36 (12%) limbs without and 11 of 98 (11%) with
      previous thrombosis (chi-square = .09, P = .77). Clinical chronic venous
      insufficiency was detected in 9% of limbs (6/67) with calf thrombi, 0% of limbs
      (0/11) with isolated femoral thrombi, and 25% of limbs (5/20) with calf and
      femoral thrombi. After photoplethysmographic assessment, only 2 of 98 (2%) cases
      were thought to be attributable to thrombosis after hip arthroplasty (95%
      confidence interval, 0.2-7.2). Despite a high incidence of deep vein thrombosis
      diagnosed on the fibrinogen uptake test after total hip arthroplasty, symptomatic
      deep chronic venous insufficiency was an unusual outcome 14 to 21 years later.

PMID- 8872572
TI  - The fully hydroxyapatite-coated total hip implant. Clinical and roentgenographic
      results.
AB  - The clinical and roentgenographic results of 54 fully hydroxyapatite (HA)-coated
      primary total hip arthroplasties in 45 patients was studied. Both the femoral and
      the acetabular components had a 200-microns coating of hydroxyapatite. The mean
      age of the patients was 54.8 years. Twenty-three patients were between 45 and 60
      years of age. There were 24 men and 21 women. Nine patients under-went bilateral
      operations. The average follow-up period was 46.9 months (range, 24-78 months).
      The average preoperative Harris hip score was 48, and the average postoperative
      Harris hip score was 94 at 1 year and 96 at 2 years. Revision surgery for
      component loosening and infection was carried out in four (7.4%) cases. There was
      aseptic loosening of the femoral component in one case (1.85%) and of the
      acetabular component in two cases (3.7%). Roentgenographic evaluation indicated
      that greater stress transfer occurs in the distal two thirds of the femoral stem.
      Proximomedial femoral neck resorption was noted in 23 cases (57.4%). Excellent to
      good clinical outcome was obtained in 89% of patients. In the short term, the
      rate of aseptic loosening of the fully HA-coated hip prosthesis in our series is
      higher than the reported rates of aseptic loosening of proximally HA-coated total
      hip implants. Controlled clinical studies would be required to evaluate the
      relative efficacy of the fully HA-coated and the proximally HA-coated hip
      prostheses.

PMID- 8872573
TI  - Aspiration as a guide to sepsis in revision total hip arthroplasty.
AB  - One hundred sixty-five patients underwent 171 preoperative aspiration arthrograms
      to evaluate a painful total hip arthroplasty. Intraoperative cultures and
      histologic specimens were obtained in all cases. Of the 166 aspirations where
      fluid was obtained, there were 140 true negative, 5 true positive, 18 false
      positive, and 3 false negative cultures. Sensitivity of hip aspiration to
      identify periprosthetic sepsis correctly was 50%; specificity was 88%. Hip
      aspiration with a 50% sensitivity rate lacks the ability to consistently predict
      those patients with occult periprosthetic sepsis. The routine use of aspiration
      in evaluation of a painful total hip is probably not indicated. Selective use in
      patients with a history of wound healing problems, radiographic changes, and
      elevated laboratory values should be considered.

PMID- 8872574
TI  - High failure rate of soft-interface stem coating for fixation of femoral
      endoprostheses.
AB  - Twenty-five total hip arthroplasties were performed in 25 patients using a
      femoral stem with a soft-interface coating of Proplast (Vitek, Houston, TX).
      Follow-up periods for 24 of the hips ranged from 82 to 104 months (median, 96
      months). Fourteen (58%) of the hips were judged to be failures, and nine of the
      failures were revised. The prostheses were thought to have failed because the
      coating was not strong enough to withstand normal weight-bearing loads. This
      inner-substance failure of the coating was seen in all revision operations.
      During these revisions, parts of the coating remained in the shaft as well as on
      the prosthesis stem. The combination of clinically manifest midthigh pain and
      radiologic scalloping and/or the pedestal sign seem to justify a strong suspicion
      of looseness of this type of cementless femoral endoprosthesis.

PMID- 8872575
TI  - Functional analysis of cemented medial unicompartmental knee arthroplasty.
AB  - Gait analysis was used to study patients who underwent cemented medial
      unicompartmental knee arthroplasty (UKA) for medial compartment degenerative knee
      disease. All had excellent clinical function of the operated knee, with minimal
      involvement of other joints. Ten patients met the inclusion criteria for this
      study. Gait findings from this study group, as well as those from a similar
      cohort of patients who had undergone total knee arthroplasty (TKA), were compared
      with those for a group of normal patients. A greater percentage of patients (7 of
      10) following UKA maintained the normal biphasic flexion/extension moment pattern
      about the knee or demonstrated a quadriceps overuse pattern, when compared with
      similar groups following TKA. In addition, the adduction moment in patients
      following UKA was significantly larger than in patients following TKA. The
      postoperative limb alignment correlated with the peak adduction moment recorded
      during the patient's gait analysis. The postoperative alignment may explain the
      differences in the adduction moment between the UKA and TKA patients, as there
      tended to be residual varus in the UKA population. The results of this study
      imply that preservation of the anterior cruciate ligament during UKA allows
      patients to maintain normal quadriceps mechanics, and that residual varus
      alignment subjects a medial UKA to higher loads.

PMID- 8872576
TI  - Bipolar femoral head arthroplasty in osteoarthritis. A prospective study with a
      minimum 5-year follow-up period.
AB  - Primary bipolar femoral head arthroplasties performed on 100 osteoarthritic hips
      were studied to a minimum of 5 years after surgery. All arthroplasties were
      performed on physically active patients. At a mean follow-up period of 5.5 years,
      The Hospital for Special Surgery hip scores were good to excellent in 96 hips.
      Transient startup soreness constituted the most frequent complaint, occurring in
      34 hips. Three hips had more persistent pain localized to the acetabulum,
      necessitating revision to fixed sockets, which alleviated the symptoms. Four
      additional hips, in heavy, active men, developed polyethylene fatigue fracture
      and component disassembly. Acetabular migration of more than 5 mm developed in
      one hip. Motion, as determined radiologically, occurred primarily at the inner
      bearing. There were no dislocations or infections in the series. The Bateman
      bipolar prosthesis provides generally good results in osteoarthritic hips. The
      shorter operating time and the case of revision are special advantages of bipolar
      devices. Start-up soreness and stiffness is a shortcoming in approximately one
      third of cases. Component disassembly in heavy, active men is a problem and the
      bipolar arthroplasty should be avoided in these patients. Start-up soreness was a
      significant problem in particular.

PMID- 8872577
TI  - Correlation of measured range of hip motion following total hip arthroplasty and
      responses to a questionnaire.
AB  - Twenty-eight patients (with 30 primary and 8 revision total hip arthroplasties)
      completed a standardized questionnaire containing the Western Ontario and
      McMaster Universities (WOMAC) osteoarthritis index and Harris hip score questions
      prior to an office visit a minimum of 1 year after surgery. The range of hip
      motion measured by an orthopaedic surgeon was compared with the responses to
      questions on stiffness and function as well as with global scores in the WOMAC
      osteoarthritis index. Patient responses to the questions asking if they could cut
      their toenails on the operated side and the Harris hip score question asking if
      they could put on socks and tie a shoe correlated significantly with
      postoperative hip motion (P < .005). The WOMAC global pain and stiffness scores
      did not correlate with range of motion. The WOMAC physical function score
      correlated significantly only with hip flexion (P < .05). Of the WOMAC physical
      function questions, difficulty bending to pick an object off the floor (P < .05)
      and getting on and off the toilet (P < .05) correlated with the sum of the range
      of motion in all planes and weighted Harris hip score range of motion
      calculation. These data suggest that the points allocated in the Harris hip score
      for range of motion can be estimated reasonably accurately from questionnaire or
      phone response to a series of questions on a standardized questionnaire. The
      question on ability to cut toenails or the Harris hip score question regarding
      ability to put on socks and tie a shoe correlated with the most individual planes
      of motion, but several WOMAC physical function questions also correlated with
      total and weighted range of motion calculations.

PMID- 8872578
TI  - Changes in femoral cortical dimensions after uncemented revision hip
      arthroplasty. Radiological results with the porous-coated bi-metric femoral stem
      prosthesis in 15 asymptomatic cases.
AB  - The radiographic results of 15 uncemented femoral revisions after a minimum
      follow-up period of 2 years are reported. Digital imaging was used to quantify
      the remodeling of the cortical bone. A method using computer-assisted video
      densitometry was developed and radiographs were scanned and digitized by a
      computer. The femoral cortex in five regions, as well as the endosteal diameter,
      was determined. After rearthroplasty, there was a significant loss in cortical
      bone with widening of the medullary canal. The periosteal diameter did not
      change. This endosteal resorption could contribute to further aseptic loosening.
      In addition, it could be an explanation of the primary prosthetic failure; one
      mode of failure could be an accelerated rate of endosteal expansion in a subgroup
      of the general population after hip arthroplasty.

PMID- 8872579
TI  - Influence of the Crowe rating on the outcome of total hip arthroplasty in
      congenital hip dysplasia.
AB  - Few studies have examined the relationship between the severity of congenital
      dysplasia of the hip (CDH) and the clinical outcome of total hip arthroplasty.
      The authors have used a prospective design to study this question, using the
      Crowe grade to assess the severity of CDH. There were 71 patients with CDH
      operated on using the S-ROM total hip (Joint Medical Products, Stamford, CT); the
      control group was composed of 22 patients without CDH operated on using the same
      implant during the same period as the CDH patients. The patients with mild CDH
      did not have a different outcome from the patients without CDH with respect to
      Harris hip score or limp. The higher the Crowe grade, the more complications
      occurred. It was also found that the patients in whom the true acetabulum was not
      used had a significantly higher incidence of limp.

PMID- 8872580
TI  - Use of iliofemoral distraction in reducing high congenital dislocation of the hip
      before total hip arthroplasty.
AB  - The iliofemoral distraction with Wagner's apparatus was conducted in 20 adult
      patients with untreated unilateral congenital dislocation of the hip (Crowe group
      IV) before total hip arthroplasty. During the distraction period of 8 to 17 days,
      this technique had effectively reduced high dislocation of 4.5 cm (range, 3.5-5
      cm). No pin-tract infection was encountered. Surgical difficulties in total hip
      arthroplasty for these patients were reduced. Potential problems, such as
      irreducibility, overshortening, nerve palsy, and displaced femoral fractures,
      were avoided. At an average follow-up period of 43 months (range, 25-63 months),
      all patients have excellent or good results, with an average Harris hip score of
      94.3 (range, 84-100). Leg length was restored. The iliofemoral distraction is
      valuable prior to difficult total hip arthroplasty for high dislocation.

PMID- 8872581
TI  - Monitoring the integrity of the cement-metal interface of total joint components
      in vitro using acoustic emission and ultrasound.
AB  - Debonding of the cement-metal interface of cemented femoral components of total
      hip arthroplasty has been shown from clinical and autopsy material to be a common
      occurrence. Experimentally, debonding has been shown to increase markedly the
      strains in the adjacent cement mantle. Studies of autopsy-retrieved specimens
      demonstrate that debonding of the cement-metal interface is a key initiating
      event in loosening of cemented femoral components of total hip arthroplasty.
      However, both the radiographic and autopsy evidence of cement-metal interfacial
      debonding exist after the fact, that is, after debonding has occurred. The lack
      of prospective data showing that debonding does indeed occur under physiologic
      loading and occurs prior to other forms of failure of fixation leaves uncertain
      the issue of debonding and its role in initiating loosening of cemented femoral
      components. Knowing when, where, and to what extent the cement-metal interface
      debonds is critical information in understanding the process of loosening of
      cemented femoral components. Such information would contribute to improving the
      durability of stems and improving cementing techniques. In this study, the two
      nondestructive techniques of acoustic emission and ultrasonic evaluation of the
      cement-metal interface of cemented femoral stems of total hip arthroplasty were
      combined to investigate when, where, and to what extent cement-metal debonding
      occurred in vitro in simulated femurs loaded physiologically in fatigue in
      simulated single-leg stance. Debonding of the cement-metal interface of a
      cemented femoral component in this model was both an initiating event and a major
      mechanism of compromise of the cement-metal interface. Additional acoustic
      emission signals arose from cracks that developed in the cement.

PMID- 8872582
TI  - Wear of the polyethylene liner-metallic shell interface in modular acetabular
      components. An in vitro analysis.
AB  - The purpose of this study was to determine the effect of compression cycles and
      wear patterns on the polyethylene liner-metallic shell interface in modular
      acetabular components. Articular frictional torque was also measured. Modular
      acetabular components from five manufacturers were tested. The polyethylene
      liners were sputter coated with gold on the convex surface to enhance the
      visualization of wear and deformation patterns. Each component was cycled for 10
      million cycles in a hydraulic fatigue testing machine. Frictional torque was
      measured prior to the start of the cyclic loading and in increments of 2 million
      cycles. Frictional torque was significantly lower in the design with an enhanced
      polyethylene liner. Abrasion of the gold from the convex surface of polyethylene
      liners varied from 2 to 23% between designs. Extrusion of the polyethylene into
      the screw holes in the metallic shells was universal. Three modes of damage
      (burnishing, punch-out, and gouging) were identified on the convex surface of the
      polyethylene liner. Abrasion of the gold from the convex surface of the
      polyethylene varied greatly between designs. This is indicative of relative
      motion between the polyethylene liner and the metallic shell. This motion must be
      minimized to limit the generation of wear debris from the convex surface of the
      polyethylene. Several aspects of modular acetabular component design could be
      implemented to potentially reduce wear, including limiting the number of holes
      available for screw placement, smoothing out the edges of the screw holes to
      avoid punch-out, and avoiding supplemental fixation of the liner unless it is
      essential to prevent motion between the liner and the metallic shell.

PMID- 8872583
TI  - Compartment syndrome of the buttock following a total hip arthroplasty.
AB  - An elevation of the interstitial pressure in a closed osseofascial compartment
      results in compartment syndrome. This may be caused by a decrease in compartment
      volume or an increase in compartment contents. The gluteal compartment syndrome
      is rare. Because the gluteal region has a large volume, this compartment requires
      a massive increase in content to cause a compartment syndrome. Also, this
      compartment blends anatomically with the muscles of the thigh, allowing
      extravasation of blood outside the compartmental envelope. This case report is of
      a patient whose medial circumflex femoral artery was severed during a total hip
      arthroplasty through a posterior approach leading to compartment syndrome of the
      buttock. Although this clinical presentation has not been described as
      compartment syndrome, one similar presentation was described in the literature.

PMID- 8872584
TI  - Delayed failure of meniscal bearing elements in total knee arthroplasty.
AB  - Dislocation and early fracture of meniscal bearing elements have been reported
      after New Jersey low-contact-stress (DePuy, Warsaw, IN) total knee arthroplasty.
      Delayed wear and subsequent failure of meniscal bearing elements in two cases, 8
      and 9 years after surgery, are reported.

PMID- 8872585
TI  - Periprosthetic metastatic carcinoma. Pitfalls in the management of two cases
      initially diagnosed as osteolysis.
AB  - Periprosthetic osteolysis is a well-described phenomenon associated with total
      hip arthroplasty. Two cases are presented in which apparently healthy patients
      developed lytic lesions adjacent to cementless hip implants. Despite atypical
      features, the lesions were initially attributed to wear debris-induced
      osteolysis, and it was discovered during revision surgery that metastatic tumor
      was present. For one patient, if the initial diagnosis had been correct,
      subsequent surgery and related complications may have been avoided. It is
      important to consider the entire differential of radiolucent bone lesions
      whenever a patient presents with periprosthetic osteolysis. If revision surgery
      is not warranted on the basis of loosening, then a thorough medical examination,
      close follow-up evaluation, and/or biopsy should be performed to rule out
      metastatic disease.

PMID- 8872586
TI  - Titanemia from total knee arthroplasty. A case resulting from a failed patellar
      component.
AB  - The subject of this case report is a patient with elevated serum levels of
      titanium (77 parts/billion [ppb]; normal, 3.3 ppb) and vanadium (0.38 ppb;
      normal, 0.17 ppb) resulting from excessive wear of a metal-backed patellar
      component in a total knee arthroplasty. The patellar component was worn through
      both its polyethylene and metal backing as a result of abnormal contact between
      the patellar and femoral components. Scanning electron microscopic examination of
      the ingrowth surface of the patellar component indicated that particle debonding
      occurred as a result of overloading of the sintered neck regions at the particle
      substrate interface, suggesting a possible damage during initial insertion of the
      device, which may have predisposed it to loosening and abnormal contact with the
      femoral component. Wear particles resulted in staining of the tissues within the
      knee and an inflammatory and immune response in the synovium consisting of giant
      cells and T lymphocytes. The serum metal levels were reduced 22 weeks after
      replacing the patellar component; however, the titanium level was still slightly
      elevated (8 ppb).

PMID- 8872587
TI  - Pelvic mass caused by polyethylene wear after uncemented total hip arthroplasty.
AB  - A 50-year-old man developed a pelvic mass following uncemented total hip
      arthroplasty. The mass communicated with the hip via an acetabular defect after
      loosening of the acetabular component. Operative and histologic findings revealed
      a foreign body reaction to polyethylene debris. Revision arthroplasty and
      excision of the pelvic mass were performed successfully through a single
      incision. A mass adjacent to a loose prosthesis may present as polyethylene
      failure following total hip arthroplasty. Revision arthroplasty and excision of
      the mass after an accurate diagnosis are recommended.

PMID- 8872588
TI  - An analysis of a retrieved Prodigy femoral prosthesis.
AB  - Radiographic and histologic data of an autopsy-retrieved femur containing a
      Prodigy stem (DePuy, Warsaw, IN) in situ for 26 months were analyzed. The Prodigy
      is a porous-coated Anatomic Medullary Locking stem modified with a smooth groove,
      the Redux Groove, on its medial central portion. This Redux Groove, designed to
      increase stem flexibility and decrease periprosthetic bone resorption, decreases
      the porous surface area available for bone ingrowth. In this case, however, the
      decreased porous area did not affect diaphyseal bone ingrowth. Additionally,
      although there is a concern that the groove will provide a pathway for debris
      migration, no evidence of debris was found in the tissue at the groove site.
      Although the Redux Groove's value in decreasing periprosthetic bone loss is still
      uncertain, this case demonstrated less proximal bone loss than was reported in
      similar dual-energy x-ray absorptiometry studies of autopsy cases containing
      Anatomic Medullary Locking stems without a groove. Analysis of more cases with
      longer in situ intervals is necessary to determine if the groove decreases
      resorptive bone remodeling and if the groove becomes a conduit for particulate
      debris migration. It is emphasized that results of this one case may not be
      representative of all Prodigy cases.

PMID- 8872589
TI  - Supracondylar femoral fracture above a PFC posterior cruciate-substituting total
      knee arthroplasty treated with supracondylar nailing. A unique technical problem.
AB  - Supracondylar fracture above a total knee arthroplasty with a posterior cruciate
      substituting design presents a challenging problem to the orthopaedic surgeon.
      The standard treatment using a intramedullary rod is made difficult by the design
      of the PFC cruciate-substituting total knee arthroplasty (Johnson & Johnson
      Orthopaedics, Raynham, MA), which prevents entry of a standard supracondylar nail
      to the medullary canal of the femur. A technique for using an interlocking
      intramedullary rod to treat a supracondylar fracture above a posterior cruciate
      substituting total knee arthroplasty is described. A case is presented
      illustrating this technique.

PMID- 8872590
TI  - Prosthetic component failures in hip arthroplasty surgery.

PMID- 8872591
TI  - Daily restricted feeding effects on the circadian activity rhythms of the stripe
      faced dunnart, Sminthopsis macroura.
AB  - The effect of daily restricted feeding (RF) on the circadian wheel-running
      activity rhythms of the stripe-faced dunnart (Sminthopsis macroura) was examined.
      Dunnarts were presented with a 2-h meal in the middle of the light period of a
      14:10 light:dark (LD) cycle and during constant dim light (LL). No meal
      anticipatory activity (AA) was observed in any of the dunnarts during the
      experiment. This contrasts with previous work where AA has been reported in
      dunnarts subjected to RF. In LL, RF acted as a weak zeitgeber for the circadian
      activity rhythms of the dunnart. Evidence supporting this observation was the
      fact that 4/8 dunnarts' activity rhythms were entrained by RF, 2 showed relative
      coordination, and 1 exhibited bouncing phenomenon. In other species of marsupials
      and in rats, it has been proposed that RF entrains a food-entrainable pacemaker,
      which, in turn, entrains, via coupling, the suprachiasmatic-based, light
      entrainable pacemaker. The findings of the present study differ from those
      reported previously in that no observable AA was entrained but the light
      entrainable pacemaker was entrained by RF. In the dunnart, it remains to be
      determined whether RF directly entrains the light-entrainable pacemaker or
      whether RF entrains a food-entrainable pacemaker and in turn, via coupling, the
      light-entrainable pacemaker.

PMID- 8872592
TI  - Food as a circadian Zeitgeber for house sparrows: the effect of different food
      access durations.
AB  - House sparrows (Passer domesticus) can synchronize their circadian rhythms of
      locomotion and feeding with times of periodic food availability. In contrast to
      most mammals, which synchronize only a specific part of their circadian system
      with feeding cycles and thus express two distinct activity components, house
      sparrows synchronize their circadian activity rhythms as a whole with the food
      zeitgeber. Previous results had indicated that feeding cycles act as
      comparatively weak zeitgebers for house sparrows. In the present study,
      therefore, we investigate whether feeding schedules are weak zeitgebers in
      general or whether their impact on the circadian system of the birds depends on
      the degree of food restriction. A detailed analysis of the synchronization
      pattern under the different experimental conditions should help to clarify
      whether house sparrows use a different mechanism for food-synchronization than
      mammals. House sparrows were kept in continuous dim light and exposed to
      different feeding schedules with daily food access durations ranging from 8 to 20
      h. Many birds lost synchronization and exhibited free-running rhythms in
      locomotor and feeding activity when the daily food access duration was lengthened
      but became synchronized when the feeding duration was shortened. The
      interpretation that short food access durations represent stronger zeitgebers
      than long food access durations was supported by the occurrence of large negative
      phase-angle differences during long daily feeding schedules, contrasting with
      small and sometimes positive phase-angle differences under short food access
      durations. There were no indications that house sparrows possess a specific food
      entrainable circadian oscillator as mammals do. Rather, periodic food
      availability seems to be a zeitgeber for the whole circadian system, which,
      hence, can be synchronized both by light and food. An explanation for such
      different mechanisms of food-synchronization is offered in the feeding ecology of
      these animals. Birds may evaluate the importance of a specific feeding schedule
      as a zeitgeber either from temporal information on the duration of the daily food
      access time or from energetic considerations. The phase-angle differences
      associated with the different feeding schedules and the maintenance of daily
      activity times may ensure an appropriate temporal integration of behavior with
      specific conditions. Non-synchronized birds exhibited masking-induced feeding
      activity, which might represent an alternative means of adjusting to feeding
      cycles when synchronization cannot occur.

PMID- 8872593
TI  - Nonphotic phase-shifting and the motivation to run: cold exposure reexamined.
AB  - Circadian rhythms in rodents can be phase shifted by appropriately timed
      activity. This may be dependent on motivational context; running induced by a
      novel wheel is effective, whereas running induced by cold has been inferred to be
      ineffective. This issue was reexamined using a different cold exposure procedure.
      On the first day of constant dark, 6 h before usual dark onset, Syrian hamsters
      were exposed to cold (+/- 4 degrees C) in their home cages, or were confined to
      novel wheels for 3 h. Activity rhythms were significantly phase advanced by 92 +/
      10 min following cold exposure and 86 +/- 17 min following novel wheel running,
      compared to 13 +/- 18 min in a control condition. Most hamsters exhibited eating,
      drinking, and modest levels of wheel running (1367 +/- 292 counts/6 h) during and
      for 3 h after cold exposure. Phase shifts following cold were not affected by
      food and water deprivation but were significantly attenuated by locking the wheel
      for 6 h beginning at cold onset (24 +/- 12 min). These data indicate that cold
      induced running, even at modest levels, is an effective nonphotic Zeitgeber and
      do not provide support for a hypothesis that motivational contexts determine the
      phase-shifting value of physical activity.

PMID- 8872594
TI  - Photic entrainment in hamsters: effects of simulated twilights and nest box
      availability.
AB  - Entrainment of wheel-running activity rhythms was compared in hamsters exposed to
      daily light-dark (LD) cycles with abrupt transitions between 0 and 10 lux or with
      artificial twilights simulating summer solstice conditions at 41 degrees N
      latitude but truncated at 10 lux. The photoperiod in LD-rectangular was set at
      16.24 h, equating the total light (in lux.min) emitted under the two schedules.
      The LD cycles were maintained for 35 days and were followed by 14 days of
      constant darkness (DD). Half the animals in each condition had access to a dark
      nest box connected to the outer compartment by a tunnel, the remaining animals
      being confined to a single compartment. Body temperature and locomotor activity
      inside the nest boxes were recorded by telemetry. Movements between the nest box
      and the outer compartment were monitored and the data were used to calculate
      light exposure at different times of the day. In all groups, the phase angle
      difference between wheel-running onset and dusk was more positive than that
      between activity offset and dawn. Hamsters with access to nest boxes, however,
      had later onsets, earlier offsets, and shorter activity durations (alpha s) than
      those without. These effects could be accounted for by the difference in light
      exposure between the nest and no-nest animals, particularly light exposure in the
      morning. The inclusion of twilights also resulted in later onsets and shorter
      alpha s, but the differences were relatively small and were only observed in the
      nest animals. The day-to-day variability in activity onset was negatively
      correlated with onset time and was smaller in the twilight/nest animals than in
      the other three groups. Most animals showed an expansion of alpha during the
      first few days of DD, resulting from a rapid advance of activity onsets relative
      to offsets. The period of the rhythms, determined from the first five activity
      onsets in DD, was negatively correlated with the balance of evening and morning
      light exposure. These results are discussed in the context of nonparametric
      entrainment of compound pacemakers.

PMID- 8872595
TI  - Light-induced phase shifting of the circadian conidiation rhythm is inhibited by
      calmodulin antagonists in Neurospora crassa.
AB  - The effects of calmodulin antagonists and inhibitors of protein kinases and
      phosphatases on light-induced phase shifting were investigated in Neurospora
      crassa. Calmodulin antagonists, namely, trifluoperazine, chlorpromazine, and W-7,
      almost completely inhibited the light-induced phase shifting without having any
      effect on the circadian clock itself. Chlorpromazine was less effective in
      inhibiting the light-induced phase shifting than trifluoperazine. W-5, a
      dechlorinated analogue of W-7, failed to inhibit the light-induced phase shifting
      at the same concentration as that at which W-7 was effective. These results
      suggest that calmodulin is required during signal transduction from the light
      perceiving system to the circadian clock in N. crassa. Inhibitors of protein
      phosphorylation did not inhibit the light-induced phase shifting, although these
      inhibitors completely inhibited mycelial growth. Trifluoperazine partially
      inhibited the phosphorylation of three proteins when phosphorylation was assayed
      in vitro.

PMID- 8872596
TI  - Quantitative two-dimensional gel electrophoretic analysis of clock-controlled
      proteins in cultured chick pineal cells: circadian regulation of tryptophan
      hydroxylase.
AB  - The progression of the circadian oscillator through its cycle and the circadian
      rhythm of melatonin production in dissociated chick pineal cultures both require
      daily de novo protein synthesis during defined circadian phases. To identify
      specific proteins involved in these two processes, we have performed a
      quantitative two-dimensional polyacrylamide gel electrophoretic screen of
      proteins that are synthesized at different times of the day in chick pineal cell
      cultures. Out of approximately 700 proteins analyzed, we have identified several
      proteins whose levels of 35S incorporation oscillate in a light/dark cycle. One
      protein of 56 kDa, pI 6 (p56) undergoes a diurnal oscillation that parallels the
      melatonin rhythm, reaching a peak early in the night and falling to minimal
      levels during the day. A second protein of 22 kDa, pI 4.5 (p22) also expresses a
      diurnal rhythm in 35S incorporation; however, it peaks at the end of the night.
      The oscillations of both proteins persist, with a reduced amplitude, in constant
      darkness. Furthermore, the phases of the p56 and p22 rhythms are regulated by the
      light/dark cycle. Both p56 and p22 appear to be under direct control of the chick
      pineal circadian oscillator, and therefore can be described as "clock-controlled
      proteins." We have identified p56 as tryptophan hydroxylase by microsequencing
      and western blotting. Chick pineal tryptophan hydroxylase also expresses a 24-h
      oscillation in abundance both in vitro and in vivo. The rhythm in tryptophan
      hydroxylase expression represents a newly discovered level of regulation of the
      melatonin synthesis pathway by the circadian clock in chick pineal cells.

PMID- 8872597
TI  - Disruption of endocrine rhythms in sleeping sickness with preserved relationship
      between hormonal pulsatility and the REM-NREM sleep cycles.
AB  - In human African trypanosomiasis (sleeping sickness), sleep and wake episodes are
      sporadically distributed throughout the day and the night. To determine whether
      these sleep disturbances affect the 24-h hormone profiles and the normal
      relationships between hormone pulsatility and sleep stages, polygraphic sleep
      recordings and concomitant hormone profiles were obtained in 6 African patients
      with sleeping sickness and in 5 healthy African subjects selected from Abidjan on
      the Ivory Coast. Polysomnographic recordings were continuous, and blood was taken
      every 10 min throughout the 24-h period. Plasma was analyzed for cortisol,
      prolactin, and plasma renin activity (PRA). The 24-h rhythm of cortisol,
      considered to be an endogenous circadian rhythm, was attenuated in all of the
      patients except one. However, as in normal subjects, slow wave sleep (SWS)
      remained associated with the declining phases of the cortisol secretory episodes.
      Prolactin and PRA profiles, which are strongly influenced by the sleep-wake
      cycle, did not manifest the nocturnal increase normally associated with the sleep
      period; instead, they reflected a sporadic distribution of the sleep and wake
      episodes throughout the 24-h period. In patients with sleeping sickness as in
      normal subjects, rapid eye movement (REM) sleep began during the descending
      phases of prolactin pulses. In both groups, PRA reflected the sleep stage
      distribution with non REM (NREM) sleep occurring during the ascending phases and
      REM sleep during the descending phases of the PRA oscillations. However, in
      sleeping sickness patients, the marked sleep fragmentation often did not allow
      sufficient time for PRA to increase significantly, as is normally the case in
      subjects with regular NREM-REM sleep cycles. These results demonstrate that,
      together with the disruption of the sleep-wake cycle, there are profound
      differences in the temporal organization of the 24-h hormone profiles in humans
      with African trypanosomiasis. However, the relationship between hormonal pulses
      and specific sleep stages persists, indicating the existence of a robust link
      between hormonal release and the internal sleep structure.

PMID- 8872598
TI  - Subjective alertness rhythms in elderly people.
AB  - The aim of this study was to evaluate age-related changes in the circadian rhythm
      of subjective alertness and to explore the circadian mechanisms underlying such
      changes. Using a visual analogue scale (VAS) instrument, 25 older men and women
      (71 y and older; 15 female, 10 male) rated their subjective alertness about 7
      times per day during 5 baseline days of temporal isolation during which habitual
      bedtimes and waketimes were enforced. Comparisons were made with 13 middle-aged
      men (37-52 y) experiencing the same protocol. Advancing age (particularly in the
      men) resulted in less rhythmic alertness patterns, as indicated by lower
      amplitudes and less reliability of fitted 24-h sinusoids. This appeared in spite
      of the absence of any reliable age-related diminution in circadian temperature
      rhythm amplitude, thus suggesting the effect was not due to SCN weakness per se,
      but to weakened transduction of SCN output. In a further experiment, involving 36
      h of constant wakeful bedrest, differences in the amplitude of the alertness
      rhythm were observed between 9 older men (79 y+), 7 older women (79 y+), and 17
      young controls (9 males, 8 females, 19-28 y) suggesting that with advancing age
      (particularly in men) there is less rhythmic input into subjective alertness from
      the endogenous circadian pacemaker. These results may explain some of the
      nocturnal insomnia and daytime hypersomnia that afflict many elderly people.

PMID- 8872599
TI  - Small caliber vascular grafts. Part II: Polyurethanes revisited.
AB  - Polyurethanes are considered to be one of the most bio- and blood-compatible
      biomaterials known today. By intelligent utilization of principles governing the
      structure/property relationship of these polymers, one can generate systems which
      resemble, in principle, the physical-mechanical behavior of living tissue. Thus,
      it is not surprising that these materials played a major role in development of
      small caliber vascular grafts targeted for vascular access, peripheral and
      coronary artery bypass indications. Numerous technologies, often esoteric in
      nature, were and are utilized to generate porous, potentially multilayered
      conduits possessing some or many characteristics of natural blood vessels.
      Properties such as durability, elasticity, compliance, pulsatility, and
      propensity for healing became attainable via polyurethanes. Furthermore,
      additional surface and/or bulk modification via attachments of biologically
      active species such as anticoagulants, cell proliferation suppressants, anti
      infective compounds or biorecognizable groups are possible due to reactive groups
      which are part of the polyurethane structure. These modifications are designed to
      control or mediate host acceptance and healing of the graft. Finally, a myriad of
      practical processing technologies are used to fabricate functional grafts. Among
      those, casting, electrostatic and wet spinning of fibers and monofilaments,
      extrusion, dip coating or spraying of mandrels with polymer/additive solutions
      are often coupled with chemical-potential-difference-driven coagulation and phase
      inversion leading to grafts feeling and often behaving like natural vessels.
      Historically, the first polyurethanes utilized were hydrolytically unstable
      polyester polyurethanes containing hydrolysis-prone polyester polyols as soft
      segments, followed by hydrolytically stable but oxidation sensitive polyether
      polyols based polyurethanes. Polyether-based polyurethanes and their clones
      containing silicone and other modifying polymeric intermediates represented
      significant progress. Many viable technologies were discovered and developed
      using polyether-based polyurethanes. Chronic in vivo instability observed on
      prolonged implantation became, however, a major roadblock. The path led finally
      to the use of hydrolytically and oxidatively stable polycarbonate polyols as the
      soft segment to generate biodurable materials with resistance to biodegradation
      adequate for vascular access or perhaps peripheral graft indications. This
      biodurability needs to be further increased in order to utilize the full
      potential of polyurethanes in development of patent small caliber graft.
      Modification of both the soft and hard segments needs to be considered in order
      to maximize biodurability of both basic building blocks of the polyurethane. This
      paper reviews the achievements, discusses trends, and offers the view of the
      future in this exciting area of material/device combination.

PMID- 8872600
TI  - Aluminum polymeric implants: in vitro-in vivo evaluations.
AB  - The purpose of this investigation is to study the effect of long-term
      subcutaneous aluminum polymeric implants on aluminum release and accumulation in
      various tissues in rats. The implants were formulated using silicone rubber and
      polyurethane polymers and three different aluminum salts. The polymeric matrices
      were evaluated for in vitro release studies. These matrices released aluminum in
      vitro up to the period of four months. The aluminum matrices were implanted in
      rats and animals were sacrificed at various time intervals. Various tissues such
      as brain, kidney, liver, intestine, and heart were isolated. Aluminum in dried
      tissues was analyzed by Neutron Activation Analysis. Results from this
      investigation suggest that polymeric aluminum implants raise the aluminum
      concentration in the brain and liver. However, these implants did not increase
      aluminum levels in intestine, heart, and kidney. The polymeric aluminum implants
      could be used to establish an animal model for the neuropathology of dementia.

PMID- 8872601
TI  - The medical device industry.

PMID- 8872602
TI  - Monocyte chemoattractant protein-1 gene expression in injured pig artery
      coincides with early appearance of infiltrating monocyte/macrophages.
AB  - Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are potent
      chemokines which attract circulating monocytes and neutrophils respectively to
      inflamed tissues. JE/MCP-1 gene expression has been previously studied in rabbit
      aortae after endothelial denudation and the rapid appearance of this transcript
      was thought to precede emigration of phagocytes. We now report MCP-1 gene
      expression following de-endothelialization of iliac arteries in the pig, a
      species which can develop spontaneous atherosclerosis. Using Northern blot
      analysis, we demonstrated that MCP-1 mRNA was rapidly induced in pig arteries at
      2 h and continued to increase to reach a maximum at 8 h before returning to low
      levels at 16-24 h after injury. The increase seen for MCP-1 mRNA at 8 h was also
      observed for IL-8 mRNA but was not apparent for growth-related gene expressions,
      urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor
      1 (PAI-1). Since smooth muscle cells, endothelial cells, and phagocytes are all
      capable of expressing MCP-1, we examined pig arteries for immunostaining using a
      monoclonal antibody to human MCP-1 (5D3-F7). At 8 h after injury, the predominant
      cell type staining positive for MCP-1 was the monocyte/macrophage. Staining was
      also observed in occasional scattered neutrophils, but MCP-1 protein could not be
      detected in smooth muscle cells or on extracellular matrix within the sensitivity
      constraints posed by our methodology. Our results are consistent with invading
      monocyte/macrophages having a major input into the production of this chemokine
      in the arterial wall following injury. The fact that MCP-1 expression accompanied
      monocyte/macrophage presence in damaged artery, rather than preceding it, is
      suggestive that continued MCP-1 expression is required for functions other than
      chemoattraction.

PMID- 8872603
TI  - Transcriptional control of the heme oxygenase gene in mouse M1 cells during their
      TPA-induced differentiation into macrophages.
AB  - It has long been known that heme oxygenase (HO) is a key enzyme in heme
      catabolism and recently it was also found to acts as an oxidative stress protein
      to produce carbon monoxide (CO), which has similar actions to those of nitrogen
      monoxide (NO). Therefore, we examined transcriptional control of the HO gene in
      mouse M1 (myeloleukemia) cells during their differentiation into macrophages.
      Since the promoter region of this gene is known to have a TPA-responsive element
      (TRE), its expression might be regulated by a C-kinase signal transduction
      pathway. Then we investigated the activation of the HO gene after treatment of M1
      cells with TPA and inhibitors of C-kinase. When M1 cells were treated with TPA,
      they differentiated into macrophage-like cells. Upon treatment with TPA, H2O2 was
      produced first, the nuclear proto-oncogenes fos and jun were activated, and then
      the HO gene was activated. The extent of transcriptional activation of the fos,
      jun, and HO genes in M1 cells treated with TPA was reduced by a specific
      inhibitor of C-kinase and a scavenger of oxygen radicals. When M1 cells were
      treated with H2O2, essentially the same level of transcription of the HO gene was
      observed, but the extent of transcriptional activation of the fos and jun genes
      was about half of the treatment with TPA. Super-shift assays using the TRE of the
      HO gene revealed that the Fos and Jun proteins from nuclei of M1 cells treated
      with TPA bound to the TRE, and same assays using DNA with the NF-kappa B motif
      also revealed that the active NF-kappa B protein from M1 cells treated with H2O2
      or TPA also bound to the corresponding motif. These results strongly suggest that
      the HO gene in M1 cells is activated by TPA through a production of H2O2, an
      oxidative activation pathway of NF-kappa B, and a signal-transduction pathway
      that involves C-kinase during the differentiation of macrophages that occurs upon
      treatment with TPA.

PMID- 8872604
TI  - High-affinity nuclear receptor binding of 20-epi analogues of 1,25
      dihydroxyvitamin D3 correlates well with gene activation.
AB  - The hormone 1,25-dihydroxyvitamin D3 (VD) has the potential for clinical use in
      several diseases, such as cancer, osteoporosis, and psoriasis. The action of VD
      is mediated by primary responding genes that contain in their promoter region a
      binding site for the transcription factor VDR. Most of the known VD response
      elements are formed by a direct repeat of two hexameric core binding motifs
      spaced by three nucleotides (DR3) bound by a heterodimer of VDR and the retinoid
      X receptor (RXR). Various VD analogues have been developed in order to optimize
      the therapeutic profile of VD. This report presents a novel experimental system
      that may help in the understanding of the structural basis for the high potency
      of a VD analogue like KH1060, which is a 20-epi-22-oxa-derivative of VD. In human
      breast cancer cells, MCF-7, the half-maximal gene activation values for KH1060
      and seven of its structural precursors were determined on a DR3-type VD response
      element. These eight analogues cover conservative structural changes from 20-epi
      VD (MC1288) to KH1060. With a modified version of the limited protease digestion
      assay the functional affinity of the analogues to VDR was measured. The
      functional receptor affinity of the eight analogues was found to be directly
      proportional to their potency in VDR-RXR-mediated gene activity.

PMID- 8872605
TI  - Comparison of the subcellular distribution of G-proteins in hepatocytes in situ
      and in primary cultures.
AB  - The subcellular localization of the heterotrimeric G-proteins in hepatocytes in
      situ was compared to that in hepatocytes in primary culture. The ability of
      various ligands to activate adenylyl cyclase (AC) in membrane preparations was
      also investigated. In hepatocytes in situ the G proteins were mainly localized at
      the plasma membrane while in hepatocytes in culture they were predominantly
      cytoplasmic. The localization of the G-proteins in hepatocytes in situ correlates
      with their role in signal transduction. In homogenates prepared from the cultured
      cells, ligands which stimulate AC via Gs alpha were without effect, which was
      consistent with the localization of Gs alpha in the cytoplasmic and nuclear
      compartments. The "relocalization" of the G proteins to the cytoplasm when cells
      are cultured suggests that transmembrane signalling may be regulated by cell
      differentiation and cell-cell and cell-extracellular matrix interactions.

PMID- 8872606
TI  - Soluble factors secreted by activated T-lymphocytes modulate the transcription of
      the immunosuppressive cytokine TGF-beta 2 in glial cells.
AB  - Coordination of the immune response to injury or disease in the brain is
      postulated to involve bi-directional discourse between the immune system and the
      central nervous system. This cross communication involves soluble mediators,
      including various growth factors, cytokines, and neuropeptides. In this report,
      we demonstrate that the supernatant from activated T-lymphocytes is able to
      induce the transcription of a potent cytokine, TGF-beta 2 in glial cells. The
      activating stimulus invokes signaling mechanisms distinct from known kinase or
      protease pathways. Activation of TGF-beta 2 transcription correlates with the
      loss of binding activity for an 80 kDA glial labile repressor protein, GLRP, to a
      responsive region within the TFG-beta 2 promoter. Although GLRP shares some
      characteristics with the inducible transcription factor AP-1, it appears to be
      distinct from known AP-1 family members. These data along with previous
      observations demonstrating the potent immunosuppressive activity of TGF-beta 2,
      support a model for a feedback mechanism between the activated T-lymphocytes and
      astrocytes via TGF-beta 2 to regulate the immune response.

PMID- 8872608
TI  - Basic fibroblast growth factor: an autocrine growth factor for epiphyseal growth
      plate chondrocytes.
AB  - Basic fibroblast growth factor (bFGF) is a permissive mitogen for cultured
      chondrocytes and has been localized in the specific zones of the epiphyseal
      growth plate. In this study, we demonstrate that bFGF present in cartilage
      originates from within the cellular constituents of this tissue. Utilizing
      reverse transcription coupled to the polymerase chain reaction (PCR), bFGF mRNA
      was found in extracts of cartilage tissue. Immunocytochemical studies revealed
      that bFGF was present intracellularly in freshly isolated proliferative
      chondrocytes and in the extracellular matrix (ECM) after 24 h of culture. Western
      blot analysis of protein extracts from isolated proliferative chondrocytes
      identified a bFGF immunoreactive species with a molecular weight of approximately
      18 kDa. In situ hybridization confirmed the presence of bFGF mRNA in freshly
      isolated proliferative chondrocytes. The bFGF in the ECM seemed to be sequestered
      and not available for biological activity, since these cells still required
      exogenous bFGF for cell proliferation. This sequestered bFGF could be released to
      stimulate cell proliferation when cultures were treated with plasmin, a
      proteolytic enzyme. These data support the hypothesis that bFGF is synthesized by
      chondrocytes and functions as an autocrine/paracrine mitogen via its deposition
      into the ECM with subsequent release from the ECM of cartilage being a critical
      step in biological activity. In addition, the study provides further evidence
      that locally produced bFGF plays an important role in normal growth and
      development of cartilage tissue.

PMID- 8872607
TI  - Staurosporine induces neurite outgrowth in neuronal hybrids (PC12EN) lacking NGF
      receptors.
AB  - A novel neuronal model (PC12EN cells), obtained by somatic hybridization of rat
      adrenal medullary pheochromocytoma (PC12) and bovine adrenal medullary
      endothelial (BAME) cells, was developed. PC12EN cells maintained numerous
      neuronal characteristics: they expressed neuronal glycolipid conjugates,
      synthesized and secreted catecholamines, and responded to differentiative agents
      with neurite outgrowth. PC12EN lacked receptors for EGF and both the p75 and trk
      NGF receptors, while FGF receptor expression was maintained. Staurosporine (5-50
      nM), but not other members of the K252a family of protein kinase inhibitors,
      rapidly induced neurite outgrowth in PC12EN, as also found in the parental PC12
      cells, but not in BAME cells. Similarly, both acidic and basic FGF (1-100 ng/ml)
      were neurotropic in PC12EN. In contrast to the mechanism by which FGF promoted
      neurite outgrowth in PC12EN, the neurotropic effect of staurosporine did not
      involve activation of established signalling pathways, such as tyrosine
      phosphorylation of erk (ras pathway) or SNT (a specific target of neuronal
      differentiation). In addition, staurosporine induced the tyrosine phosphorylation
      of the focal adhesion kinase p125FAK. However, since the latter effect was also
      observed with other protein kinase inhibitors of the K252a family, which induced
      PC12EN cells flattening but no neurite extension, we propose that FAK tyrosine
      phosphorylation may be related to ubiquitous changes in cell shape. We anticipate
      that PC12EN neuronal hybrids will become useful models in neuroscience research
      for evaluating unique cellular signalling mechanisms of novel neurotropic
      compounds.

PMID- 8872609
TI  - Filamin translocation is an early endothelial cell inflammatory response to
      bradykinin: regulation by calcium, protein kinases, and protein phosphatases.
AB  - Endothelial cell (EC) cytoskeletal proteins are one of the earliest primary
      targets of second messenger cascades generated in response to inflammatory
      agonists. Actin binding proteins, by modulating actin gelation-solation state and
      membrane-cytoskeleton interactions, in part regulate cell motility and cell-cell
      apposition. This in turn can also modulate interendothelial junctional diameter
      and permeability. Nonmuscle filamin (ABP-280), a dimeric actin-crosslinking
      protein, promotes orthogonal branching of F-actin and links microfilaments to
      membrane glycoproteins. In the present study, immunoblot analysis demonstrates
      that filamin protein levels are low in sparse EC cultures, increase once cell
      cell contact is initiated and then decrease slightly at post-confluency. Both
      bradykinin and ionomycin cause filamin redistribution from the peripheral cell
      border to the cytosol of confluent EC. Forskolin, an activator of adenylate
      cyclase, blocks filamin translocation. Bradykinin activation of EC is not
      accompanied by significant proteolytic cleavage of filamin. Instead, intact
      filamin is recycled back to the membrane within 5-10 min of bradykinin
      stimulation. Inhibitors of calcium/calmodulin dependent protein kinase (KT-5926
      and KN-62) attenuate bradykinin-induced filamin translocation. H-89, an inhibitor
      of cAMP-dependent protein kinase, causes translocation of filamin in unstimulated
      cells. Calyculin A, an inhibitor of protein phosphatases, also causes
      translocation of filamin in the absence of an inflammatory agent. ML-7, an
      inhibitor of myosin light chain kinase and phorbol myristate acetate, an
      activator of protein kinase C, do not cause filamin movement into the cytosol,
      indicating that these pathways do not modulate the translocation. Pharmacological
      data suggest that filamin translocation is initiated by the calcium/calmodulin
      dependent protein kinase whereas the cAMP-dependent protein kinase pathway
      prevents translocation. Inflammatory agents therefore may increase vascular
      junctional permeability by increasing cytoplasmic calcium, which disassembles the
      microfilament dense peripheral band by releasing filamin from F-actin.

PMID- 8872610
TI  - Sexual differences in 5'-deiodinase activity in the Harderian gland of Syrian
      hamsters and the effect of pinealectomy: regulation by androgens.
AB  - Sexual differences on thyroxin 5'-deiodinase (5'-D) in the Harderian gland of
      Syrian hamsters were investigated. We compared the 24-h profile of 5'-D activity
      in male and female hamsters, observing a clear rhythm in males but not in
      females. Female values were always significantly higher than male ones. After
      pinealectomy day/night variations in male 5'-D activity at the time points
      studied were abolished, results that are in correlation with serum thyroid
      hormones. We also studied the regulation by androgen of the enzyme activity.
      Basal 5'-D activity increased in castrated males and levels fell when animals
      were implanted with testosterone or its product 5 alpha-dihydrotestosterone
      (DHT). Female 5'-D activity was also inhibited by androgens. As only the addition
      of DHT in the presence of epitestosterone, an inhibitor of the conversion of
      testosterone on DHT, in castrated males was able to decrease 5'-D activity to the
      control animal levels, we suggest a probable direct effect of DHT by itself.

PMID- 8872611
TI  - E2F1 inhibition of transcription activation by myogenic basic helix-loop-helix
      regulators.
AB  - Cellular transcription factor E2F1 is thought to regulate the expression of genes
      important for cell cycle progression and cell proliferation. Deregulated E2F1
      expression induces S-phase entry in quiescent cells and inhibits myogenic
      differentiation. We show here that E2F1 inhibits the activation of gene
      transcription by myogenic basic helix-loop-helix proteins myoD and myogenin.
      Transfection assay using different deletion constructs indicates that both the
      DNA binding and the transactivation domains of E2F1 are required for its
      inhibition of myoD transcription activation. However, the retinoblastoma protein
      (RB) binding domain is not required. Furthermore, co-transfection with the RB,
      which inhibits the transcription activity of E2F1, can also repress E2F1
      inhibition of myoD transactivation. These results suggest an essential role of
      E2F1-mediated transcription in its inhibition of myogenesis.

PMID- 8872612
TI  - Regulation of lysyl oxidase and cyclooxygenase expression in human lung
      fibroblasts: interactions among TGF-beta, IL-1 beta, and prostaglandin E.
AB  - Prostaglandin E2, transforming growth factor-beta, and interleukin-1 beta
      variably regulate the expression of cyclooxygenase 1, cyclooxygenase 2, and lysyl
      oxidase in IMR90, human embryo lung fibroblasts. Prostaglandin E2 at 100 nM
      upregulates cyclooxygenase 1 mRNA by approximately three-fold while it
      downregulates lysyl oxidase mRNA levels. Notably, prostaglandin E2 suppresses the
      enhancing effect of TGF-beta on basal levels of lysyl oxidase mRNA. These changes
      in steady state mRNA levels reflect transcriptional level control, at least in
      part. Corresponding changes are seen in the protein levels of lysyl oxidase,
      cyclooxygenase 1 and cyclooxygenase 2 and catalytic activities of these enzymes,
      including net prostaglandin E2 synthesis. Cyclooxygenase 2 mRNA(t1/2, 30 min) is
      considerably less stable than that of cyclooxygenase 1 (t1/2, 4 h) while lysyl
      oxidase mRNA is unusually stable (t1/2 > 14 h). Taken together with the differing
      kinetics with which these genes respond to perturbation by these cytokines, the
      present results suggest a coordinated, autocrine-like mechanism of regulation of
      cyclooxygenase 1 and cyclooxygenase 2 and further point to the potential of their
      metabolic product, prostaglandin E2, to suppress the expression of lysyl oxidase
      in the inflammatory response to injury.

PMID- 8872613
TI  - Retinoblastoma protein family in cell cycle and cancer: a review.
AB  - Two genes, p107 and Rb2/p130, are strictly related to RB, the most investigated
      tumor suppressor gene, responsible for susceptibility to retinoblastoma. The
      products of these three genes, namely pRb, p107, and pRb2/p130 are characterized
      by a peculiar steric conformation, called "pocket," responsible for most of the
      functional interactions characterizing the activity of these proteins in the
      homeostasis of the cell cycle. The interest in these genes and proteins springs
      from their ability to regulate cell cycle processes negatively, being able, for
      example, to dramatically slow down neoplastic growth. So far, among these genes,
      only RB is firmly established to act as a tumor suppressor, because its lack-of
      function is clearly involved in tumor onset and progression. It has been found
      deleted or mutated in most retinoblastomas and sarcomas, but its inactivation is
      likely to play a crucial role in other types of human cancers. The two other
      members of the family have been discovered more recently and are currently under
      extensive investigation. We review analogies and differences among the pocket
      protein family members, in an attempt to understand their functions in normal and
      cancer cells.

PMID- 8872614
TI  - Interactions among metabolic rate, hypoxia, and control of breathing.
AB  - This review attempts to emphasize the fact that the interpretation of the
      ventilatory response to hypoxia may be complicated by the reduction in metabolic
      rate that is often associated with hypoxia. The hypoxic hypometabolism is more
      apparent when oxygen consumption is relatively high, either in small or young
      mammals at subnormal ambient temperatures or in larger mammals exposed to cold.
      This hypometabolism is not mediated by an activation of the arterial
      chemoreceptors and, furthermore, may result from a decrease in arterial oxygen
      content independent of the arterial PO2. Substantial experimental evidence
      supports the hypothesis of a lowering of the thermoregulatory set point during
      hypoxia through a direct action on central neural structures. The ventilatory
      response to hypoxia, which may appear blunted or depressed, especially in small
      animals exposed to cold, should in fact be reevaluated by taking into account the
      hypometabolism and hypothermia associated with hypoxia. Finally, it is emphasized
      that the mechanisms involved in control of body temperature and those that
      account for the interactions with hypoxia are located in the hypothalamus. This
      suggests that common integrative structures are probably involved in the
      metabolic and ventilatory responses to hypoxia.

PMID- 8872615
TI  - Autoregressive spectral analysis of phrenic neurogram during eupnea and gasping.
AB  - During hypoxic gasping, the phrenic neurogram (PN) has a steeper rate of rise, an
      augmented amplitude, and a shorter duration than is seen during eupnea. Because
      hypoxia reduces neuronal activity, we hypothesized that gasping would be
      characterized in the frequency domain by enhanced low-frequency power compared
      with eupnea. Autoregressive (AR) spectral analysis of the PN in chloralose
      anesthetized, vagotomized, peripherally chemodenervated cats was performed during
      eupnea and hypoxic gasping. During eupnea, significant spectral peaks were seen
      at 41 +/- 2 and 93 +/- 2 (SE) Hz. In all cats, the 41-Hz spectral peak
      disappeared during hypoxic gasping and was replaced by a high-power, low
      frequency peak at 26 +/- 1 Hz. No consistent change in the frequency or power of
      the high-frequency spectral peak was seen during gasping. To determine whether
      changes in the AR spectrum of the PN during gasping result from augmented
      respiratory output, we compared the AR spectra of the PN during gasping,
      hypercapnia (end-tidal CO2 fraction = 0.09), and carotid sinus nerve stimulation.
      Unlike during gasping, there was no shift in power toward lower frequencies
      during hypercapnia and carotid sinus nerve stimulation. We conclude that the
      spectral characteristics of gasping, loss of the medium-frequency peak and the
      appearance of low-frequency (< 30-Hz) power, are unique to this respiratory
      pattern.

PMID- 8872616
TI  - Exogenous infusion of adenosine depresses whole body O2 use in fetal/neonatal
      sheep.
AB  - To examine a possible metabolic regulatory role for adenosine, infusions of
      adenosine and adenosine deaminase were given to 11 near-term fetal sheep during
      the simulation of birth in utero. Fetal arterial blood gases, the concentration
      of a number of metabolites, insulin, and whole body O2 consumption (VO2) were
      measured. After intrauterine ventilation and cord occlusion, fetal/neonatal VO2,
      measured by closed-circuit respirometry, averaged 11.0 +/- 1.1 (SE) ml (STPD).min
      1.kg fetal wt-1 and plasma adenosine concentration ([Ado]) was 1.29 +/- 0.21
      microM. Infusion of adenosine (1.5 mumol.min-1.kg-1) during the next 30-min
      interval increased [Ado] to 1.57 +/- 0.28 microM (not significant) and decreased
      VO2 to 7.7 +/- 0.5 ml.min-1.kg-1 (P < 0.05). The infusion reduced systolic blood
      pressure by 19% (P < 0.01) and diastolic blood pressure by 25% (P < 0.01) and
      increased heart rate by 19% (P < 0.01). At the highest rate of adenosine infusion
      studied (6 mumol.min-1.kg-1), [Ado] increased to 4.27 +/- 0.46 microM (P < 0.001)
      and VO2 did not measurably decline further, although there were further decreases
      in blood pressure and increases in heart rate. After administration of adenosine
      deaminase, [Ado] decreased to 0.58 +/- 0.13 microM (P < 0.05), whereas VO2
      increased to 11.2 +/- 0.8 ml.min-1.kg-1 (P < 0.05); blood pressure and heart rate
      returned to basal levels. The dependence of VO2 on [Ado] is described by the
      relationship VO2 = 6.14 + 4.89 exp(-0.45[Ado]) (n = 144; r = 0.34; P < 0.001).
      Throughout the experiment, arterial O2 content and plasma glucose, lactate,
      glycerol, and fatty acid concentrations were normal or elevated, and, therefore,
      O2 lack and substrate deficiency were unlikely to have caused the reduction in
      VO2. We conclude that plasma adenosine may act as a messenger of energy status
      for the ovine fetus/neonate and may contribute thereby to a maintenance of a
      balance between O2 supply and O2 demand.

PMID- 8872617
TI  - Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and
      inhaled glucocorticoids.
AB  - Both smoking and asthma are associated with inflammatory changes in the lung,
      which may be suppressed with the help of exogenous anti-inflammatory drugs or by
      the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti
      inflammatory protein present in respiratory tract secretions. We report an
      inverse correlation between extracellular LC-1 concentration and the
      bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation
      coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from
      allergic asthmatic patients, together with positive correlations between
      extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6
      keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter
      BALF and concentration of histamine causing a 20% decrease in forced expired
      volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no
      significant difference between the LC-1 concentration in BALF from nonsmoking
      asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100
      micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin;
      n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps
      because inhaled drugs deposit predominantly in central airways, which are poorly
      represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who
      smoked had higher levels of LC-1 in their BALF than did their nonsmoking
      counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10;
      asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps
      because smokers' lungs contain more alveolar macrophages, cells that release LC
      1. We observed a positive correlation between BALF LC-1 and bronchoalveolar
      lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1
      may be part of a protective response of the lung to inflammatory insult.
      Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses
      inflammation.

PMID- 8872618
TI  - Is respiratory sinus arrhythmia a good index of cardiac vagal tone in exercise?
AB  - To assess the relative roles of neural and nonneural mechanisms in respiratory
      sinus arrhythmia (RSA) at rest and during exercise (steady-state supine cycle
      ergometry at 25% of peak oxygen uptake), we studied 10 healthy men (mean age 21
      +/- 1 yr) before (control) and during ganglion blockade (GB) with trimetaphan
      camsylate (3-5 mg/min i.v.). GB was confirmed by the abolition of the reflex
      bradycardia in response to intravenous phenylephrine and of the blood pressure
      rise with the cold pressor test. RSA was calculated from the power of the
      spectral component of the R-R interval variability centered at the breathing
      frequency. GB decreased but did not abolish RSA. At rest, this nonneural
      component of RSA was negligible, accounting for < 1% of the control RSA. During
      GB, exercise did not affect RSA significantly. However, because control RSA was
      decreased by exercise, the proportion of nonneural RSA increased by 32% (range
      from 17 to 75%). These results indicate that as the vagal tone decreases with
      exercise, an increasing proportion of RSA is due to nonneural mechanisms.

PMID- 8872619
TI  - Influence of reduced carotid body drive during sustained hypoxia on hypoxic
      depression of ventilation in humans.
AB  - To evaluate whether the intact hypoxic drive from the carotid bodies during
      sustained hypoxia is required for the generation of hypoxic depression of
      ventilation (VE), 16 volunteers were exposed to two consecutive periods of
      isocapnic hypoxia (first period 20 min; second period 5 min; end-tidal PO2 45
      Torr) separated by 6 min of normoxia. In study A, saline was given. In study B, 3
      micrograms.kg-1.min-1 i.v. dopamine (DA), a carotid body inhibitor, was given
      during the first hypoxic exposure followed by saline during normoxia and the
      second hypoxic exposure. In study C, 20 min of normoxia with DA preceded 6 min of
      normoxia and 5 min of hypoxia without DA. The first peak hypoxic VE (PHV) in
      study A was approximately 100% above normoxic VE. After 20 min of hypoxia, VE
      declined to 60% above normoxic VE. The second PHV in study A was only 60% of the
      first PHV. We relate this delayed recovery from hypoxia to "ongoing" effects of
      hypoxic depression. During DA infusion, the changes in VE due to sustained
      hypoxia were insignificant (study B). The second PHV in study B was not different
      from the PHV after air breathing in studies A and C. This indicates that the
      recovery from sustained hypoxia with a suppressed carotid body drive was complete
      within 6 min. Our results show that despite central hypoxia the absence of
      ventilatory changes during 20 min of isocapnic hypoxia due to intravenous DA
      prevented the generation of central hypoxic depression and the depression of a
      subsequent hypoxic response.

PMID- 8872620
TI  - Cardiovascular responses to beta-stimulation with isoproterenol in deep
      hypothermia.
AB  - The aim of this study was to investigate the effects of beta-stimulation in deep
      (25 degrees C) hypothermia. Cardiac catheterization was performed on seven
      anesthetized beagle dogs. They were cooled between ice bags down to 25 degrees C
      and received isoproterenol administered intravenously three times: at the normal
      body temperature (37 degrees C) before cooling, after cooling at 25 degrees C,
      and after rewarming at 37 degrees C. Circulatory function was measured for every
      1 degree C of temperature change. Isoproterenol infusion at 37 degrees C induced
      cardiac acceleration, including the increases of heart rate, cardiac output, and
      peak first derivative of the left ventricular pressure curve. Systemic vascular
      and mean outflow resistances and mean aortic pressure decreased. During cooling,
      shivering thermogenesis continued, even down to 25 degrees C. At 25 degrees C,
      cardiac acceleration after isoproterenol infusion did not exist but relaxation
      rate increased slightly. Systemic vascular and mean outflow resistances
      decreased, but left ventricular end-diastolic and filling pressures increased.
      beta-Stimulation at normal body temperature increases shivering thermogenesis
      during cooling. The venous return to the left ventricle at 25 degrees C increased
      after isoproterenol infusion while systemic vascular resistance decreased,
      indicating systemic vasodilatation. This increase in preload is probably due to
      vasoconstriction in pulmonary vessels, which may be mediated by prejunctional
      beta-adrenoceptors. For cardiac inotrophy, the isoproterenol had no
      physiologically significant effects at 25 degrees C. After rewarming at 37
      degrees C, the effects of isoproterenol were physiologically similar to the
      effects at the same temperature before cooling.

PMID- 8872621
TI  - Mediators of contraction-evoked skeletal muscle depressor response in
      anesthetized rats.
AB  - In the present study, mediators of muscle contraction-evoked cardiovascular
      responses were examined in anesthetized rats. Rhythmic contractions of the
      hindlimb triceps surae muscle were produced by stimulating the tibial nerve
      (motor threshold 22.7 +/- 2.3 microA; n = 10) by using a 1 s on-1 s off pattern.
      Mean arterial pressure (MAP) and heart rate (HR) responses were recorded before
      and after 1) muscarinic receptor blockade (atropine sulfate; 2.0 mg/kg i.v., n =
      5); 2) nitric oxide synthase inhibition with N omega-nitro-L-arginine methyl
      ester (L-NAME; 300 microM/kg i.v., n = 7); 3) beta-adrenoceptor blockade
      (propranolol; 2.0 mg/kg i.v., n = 10); and 4) bilateral adrenalectomy (n = 4).
      Rhythmic stimulation (10-s) significantly reduced MAP (P < 0.05) and elicited
      small decreases in HR that were abolished by neuromuscular blockade (n = 4).
      Atropine had no effect on MAP or HR responses to contraction. L-NAME increased
      baseline MAP (112.2 +/- 2.2 to 137.1 +/- 4.6 mmHg, P < 0.05) and attenuated
      contraction-evoked reductions of MAP (P < 0.05) without affecting HR. L-NAME
      induced response deficits were mimicked in four separate rats by elevating MAP
      with phenylephrine (7-10 micrograms.kg-1.h-1 iv) to a level not different from
      that produced by L-NAME. Bilateral adrenalectomy and propranolol did not
      significantly affect HR responses but reduced contraction-evoked decreases in MAP
      from 14.3 +/- 2.9 to 7.7 +/- 2.2 mmHg and from 13.4 +/- 1.3 to 6.3 +/- 3.1 mmHg,
      respectively (P < 0.05). Baseline MAP was unchanged. We conclude that adrenal
      catecholamines, acting at beta-adrenoceptors, contribute significantly to the
      contraction-evoked depressor response in rats. No role for muscarinic receptors
      is evident in this response. Furthermore, attenuation of depressor responses to
      contraction after nitric oxide inhibition could result from an indirect effect of
      the pressor actions of L-NAME.

PMID- 8872622
TI  - Breathing during exercise in dogs--passive or active?
AB  - The activation patterns of the costal and crural diaphragm and transversus
      abdominis muscle and their relationship to esophageal pressure (Pes) changes and
      footplant were examined in five chronically instrumented dogs which breathed at
      high frequencies at rest and during exercise. In two tracheostomized dogs,
      measurements were made of diaphragmatic length via sonomicrometry and of airflow
      and were related to diaphragmatic electrical activity and Pes. Dogs exhibited
      either a high-frequency breathing pattern, characterized by Pes changes occurring
      at 2-6 Hz, or a mixed-frequency breathing pattern, characterized by low-amplitude
      Pes oscillations (4-6 Hz) superimposed on a slower breathing rate of 0.5-1 Hz.
      Regardless of the type of breathing pattern elected or of the various breathing
      to-stride frequency ratios observed during exercise, decreases in Pes were always
      associated with phasic electromyographic activity of the costal and crural
      diaphragm and with phasic diaphragmatic muscle shortening. The transversus
      abdominis electromyographic activity coincided with an increasing Pes from peak
      negative values in resting dogs and exhibited both an expiratory and a locomotory
      modulation during exercise. Although footplant may have contributed to some
      airflow generation when dogs utilized the mixed-frequency pattern, these data
      demonstrate that the movement of air into and out of the lungs in stationary or
      exercising dogs requires phasic neural activation of the diaphragm and other
      respiratory muscles.

PMID- 8872623
TI  - Comparison of regional cerebral blood flow with transcranial magnetic stimulation
      at different forces.
AB  - This study's objective was to investigate regional cerebral blood flow (rCBF)
      within the primary motor cortex (M1) and to compare it with thresholds of
      transcranial magnetic stimulation (TMS) and electromyographic recordings during
      exertion of different force levels with the right index finger. Quantitative
      electromyographic recordings, TMS, and positron emission tomography scans were
      performed while five and six volunteers, respectively, pressed a Morse key
      repetitively or with constant force with the right hand at five different force
      levels: 5, 10, 20, 40, and 60% of the individual's maximum voluntary contraction
      (MVC). Although at 5% MVC muscle activity was restricted to the first dorsal
      interosseus muscle, superficial finger flexors, and extensors, there was
      progressive involvement of proximal muscles during finger flexion with increasing
      force. rCBF increased logarithmically in the contralateral M1 with increasing
      force. In ipsilateral M1, rCBF decreased at 5% MVC and then increased
      logarithmically at higher force levels. TMS thresholds in the contralateral
      hemisphere declined logarithmically to reach a plateau at high force levels. The
      threshold in the ipsilateral hemisphere decreased slightly at high force levels.
      The logarithmic increase of rCBF and decrease of TMS thresholds in the
      contralateral hemisphere suggest related underlying physiological phenomena;
      increased cortical synaptic activity and increased excitability. It suggested
      that the pronounced ipsilateral rCBF alterations reflect transcallosal inhibition
      and are more prominent during repetitive movements (as used in the positron
      emission tomography study) than during the generation of a constant force (as
      exerted during TMS).

PMID- 8872624
TI  - Hypoxia in vivo inhibits aldosterone synthesis and aldosterone synthase mRNA in
      rats.
AB  - Hypoxia leads to a decrease in aldosterone that cannot be entirely explained by
      extrinsic controllers of adrenal function. We have shown that acute hypoxia
      attenuates aldosterone synthesis via a direct inhibition of the function of the
      aldosterone enzyme pathway. The mechanism of the sustained decrease in
      aldosterone during chronic hypoxia is unknown. The present study evaluated the
      hypothesis that chronic hypoxia leads to a decrease in the expression of the
      steroidogenic enzyme P-450c11AS unique to the aldosterone pathway. Rats were
      exposed to 3 days of normoxia, moderate hypoxia (12% O2), or severe hypoxia (10%
      O2). Adrenal glands were removed and prepared for biochemical analysis of
      steroidogenesis in vitro (dispersed capsular cells) and for measurement of steady
      state enzyme mRNA levels by reverse-transcription competitive polymerase-chain
      reaction (RT-cPCR) and by in situ hybridization histochemistry (ISHH). Moderate
      hypoxia had no effect on steroidogenesis. Adrenal cells from rats exposed to
      severe hypoxia demonstrated a decreased conversion of corticosterone to
      aldosterone (late pathway catalyzed by P-450c11AS) without a change in the other
      mitochondrial cytochrome P-450 enzyme activities. Adrenal cells from rats exposed
      to hypoxia also demonstrated a three- to fourfold decrease in P-450c11AS mRNA
      without a change in the other mitochondrial cytochrome P-450 enzymes mRNAs, as
      determined by either RT-cPCR or ISHH. We conclude that relatively short-term
      chronic hypoxia in rats leads to a decrease in aldosteronogenesis by decreasing
      the expression of the gene for the late-pathway enzyme unique to the aldosterone
      pathway (P-450c11AS).

PMID- 8872625
TI  - Breathing and brain blood flow during sleep in patients with chronic mountain
      sickness.
AB  - Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2)
      during sleep compared with healthy high-altitude residents, but whether nocturnal
      arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We
      measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid
      artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11
      healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of
      Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB
      (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS
      controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P <
      0.05) because of more frequent apnea and hypoventilation episodes and longer
      duration of all types of episodes. SDB and unexplained arterial O2 desaturation
      caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS
      controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the
      CMS patients spent 29%, whereas the other groups spent < 4%, of the night at
      values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity
      during wakefulness was similar in CMS patients and CMS controls despite higher
      end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are
      compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both
      groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement
      sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB,
      internal carotid flow velocity increased in CMS controls but did not change in
      the CMS patients such that values were lower in the CMS patients than in CMS
      controls at the end and after SDB episodes. We concluded that SDB and episodes of
      unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a
      lack of compensatory increase in internal carotid artery flow velocity, likely
      decreased brain O2 delivery in CMS patients during a considerable portion of the
      night.

PMID- 8872626
TI  - Regional changes in capillary supply in skeletal muscle of high-intensity
      endurance-trained rats.
AB  - The objective of this study was to test the hypothesis that an endurance training
      program designed to produce recruitment of all extensor muscle fiber types during
      each exercise bout would stimulate capillary angiogenesis throughout rat
      gastrocnemius and soleus muscles. Male Sprague-Dawley rats were exercise trained
      5 days/wk for 12-14 wk with exercise bouts consisting of a combination of high
      intensity (32 m/min on a 15% incline) and long duration (90 min/day). On
      completion of high-intensity endurance training (HIET) or cage activity
      [sedentary (Sed)], rat hindquarters were vascularly isolated and perfusion fixed
      with a modified Karnovsky's fixative. Capillary supply was measured in soleus and
      gastrocnemius muscles by using Olympus Cue 2 image-analyzer software. Capillary
      supply was reflected in measurements of capillary-to-fiber ratio, capillary
      numerical density, capillary surface area density, and capillary volume density
      on transversely cut tissue sections. HIET increased citrate synthase activity by
      20 and 42% in the medial and long heads of the triceps brachii, respectively.
      Sarcomere lengths were similar in gastrocnemius and soleus muscles of Sed and
      HIET rats after fixation. All four indexes of capillary supply were significantly
      greater throughout the gastrocnemius muscle of HIET rats compared with Sed
      values. The relative increase in capillarity was greater in white than in red
      gastrocnemius muscle of HIET rats. HIET also increased capillary supply of soleus
      muscle. However, only capillary numerical density was statistically greater (19%)
      in HIET soleus compared with Sed. These results support the hypothesis that this
      training program would produce an increase in capillary supply in all extensor
      muscles.

PMID- 8872627
TI  - The study of maximal nasal inspiratory flow in humans.
AB  - During inspiration through one nostril, airflow becomes limited to a maximal
      level (VImax) when the transmural pressure (Ptm) at a flow-limiting site (FLS)
      falls below a critical level (Ptm'). We compared two methods for measuring the
      Ptm' of the nasal FLS. Each of six subjects (four normal and two with allergic
      rhinitis out of season) performed multiple inspirations through one nostril as we
      varied the resistance at the nasal opening. Studies were performed after
      application of a topical decongestant without activation of the alae nasi. We
      determined Ptm' by regressing the resulting values of VImax on the corresponding
      transnasal pressure gradients (Regression Method). We also measured Ptm' directly
      using pressure catheters to measure the pressure surrounding the FLS and the
      lateral pressure near the FLS at VImax (Catheter Method). The mean value of Ptm'
      by the Regression Method was -3.8 +/- 3.2 (SD) cmH2O. The value by the Catheter
      Method with the catheter just downstream from the nasal FLS was -3.5 +/- 2.9
      cmH2O, which correlated closely with the Ptm by the Regression Method (r = 0.98).
      Our findings suggest that the Ptm' of the nasal airway can be determined by
      either method. The Catheter Method, however, requires only one inspiratory effort
      for each determination and simultaneously localizes the nasal FLS.

PMID- 8872628
TI  - Altitude acclimatization and blood volume: effects of exogenous erythrocyte
      volume expansion.
AB  - We studied sea-level residents during 13 days of altitude acclimatization to
      determine 1) altitude acclimatization effects on erythrocyte volume and plasma
      volume, 2) if exogenous erythrocyte volume expansion alters subsequent
      erythrocyte volume and plasma volume adaptations, 3) if an increased blood oxygen
      content alters erythropoietin responses during altitude acclimatization, and 4)
      mechanisms responsible for plasma loss at altitude. Sixteen healthy men had a
      series of hematologic measurements made at sea level, on the first and ninth days
      of altitude (4,300 m) residence, and after returning to sea level. Twenty-four
      hours before the ascent to altitude, one group received a 700-ml infusion of
      autologous erythrocytes (42% hematocrit), whereas the other group received only a
      saline infusion. Erythrocyte infusion increased erythrocyte volume by
      approximately 10%, whereas saline infusion had no effect; in addition, initially
      at altitude, blood oxygen content was 8% higher in erythrocyte-infused than in
      saline-infused subjects. The new findings regarding altitude acclimatization are
      summarized as follows: 1) erythrocyte volume does not change during the first 13
      days and is not affected by prior exogenous expansion, 2) a modest increase in
      blood oxygen content does not modify erythropoietin responses, 3) plasma losses
      are related to vascular protein losses, and 4) exogenous erythrocyte volume
      expansion coincides with transient increases in plasma loss, vascular protein
      loss, and mean arterial pressure elevation. These findings better define human
      blood volume responses during altitude acclimatization.

PMID- 8872629
TI  - Electrical stimulation of the lingual musculature in obstructive sleep apnea.
AB  - The influence of lingual muscle activity on airflow dynamics in the upper airway
      was examined in nine patients with obstructive sleep apnea. Muscles that retract
      the tongue (hyoglossus and styloglossus) and protrude the tongue (genioglossus)
      were selectively stimulated electrically during sleep with fine wire electrodes
      placed intramuscularly transorally. We confirmed that stimulation with 50 Hz and
      40-microseconds pulse duration did not elicit changes in electroencephalographic
      patterns or heart rate or alter airflow after the stimulation burst had ceased.
      The highest stimulus intensity that did not arouse patients from sleep was then
      utilized to examine the effect of lingual muscle recruitment on airflow dynamics
      during steady-state periods of inspiratory airflow limitation. When applying a
      stimulus burst during single inspirations, maximal inspiratory airflow decreased
      by 239 +/- 177 ml/s (P < 0.05) during retractor stimulation, whereas maximal
      inspiratory airflow increased by 217 +/- 93 ml/s during protrusor stimulation (P
      < 0.001) compared with breaths immediately before and after the stimulated
      breath. When consecutive inspirations were stimulated repeatedly, protrusor
      stimulation decreased the frequency of obstructive breathing episodes in four
      patients breathing at 3.9 +/- 3.4 (SD) cmH2O nasal pressure. The findings suggest
      that stimulation of the lingual muscles can increase or decrease airflow
      depending on the specific muscles stimulated without arousing patients from
      sleep.

PMID- 8872630
TI  - Bromide dilution in adults: optimal equilibration time after oral administration.
AB  - Extracellular water is often estimated by bromide dilution. The time interval
      between oral administration of the dose and blood sampling varies considerably
      among studies. Because at least two processes are involved during equilibration
      (distribution of the dose and bromide leaving the body), we performed a bromide
      dilution experiment and analyzed the decay data by fitting a biexponential curve.
      The experiment was carried out in 11 healthy adults (8 women and 3 men, age 21-39
      yr). Bromide ingestion (60 mg Br/l estimated total body water) was followed by
      blood sampling at 2, 3, 4, 6, 10, 25, and 105 (or 170) h. The bromide
      concentration in serum ultrafiltrate was determined with high-performance liquid
      chromatography. The bromide concentration in serum after dose intake showed a
      significant decrease over time. One-exponent functions significantly fitted the
      data. The two-exponent functions fitted the data significantly better (F-test, P
      < 0.0001). A model combining the data from all subjects fitted just as well.
      Equilibration time can be defined as the time at which the first exponential
      function, which represents distribution of the dose, has decreased to 5% of its
      starting value. According to this model, the equilibration time of orally
      administered bromide should be 8.5-11.7 h. This can be achieved by an overnight
      equilibration.

PMID- 8872631
TI  - Chemoreceptor nerve excitation may not be proportional to catecholamine
      secretion.
AB  - Enhanced catecholamine secretion from the carotid body glomus cells is
      hypothesized to play an essential role in mediating the peripheral chemoreceptor
      response to hypoxia. To test aspects of this hypothesis, the relationship between
      catecholamine secretion and nerve activity was examined during repetitive hypoxia
      stimuli and after catecholamine depletion with reserpine. Single-fiber afferent
      serve activity was measured along with an estimate of free tissue catecholamine
      by using Nafion-coated carbon-fiber microelectrodes placed in rat carotid bodies
      in vitro. Baseline and stimulated nerve and catecholamine levels were quantified
      during repetitive stimulation (anoxia of 1-min duration; PO2 = 0 Torr at nadir,
      repeated each 200 s). Peak stimulated catecholamine progressively decreased from
      26.4 +/- 2.6 microM for the first stimulus to 7.5 +/- 0.9 microM for the fifth
      stimulus (n = 15), but peak nerve activity was much less affected (23.0 +/- 1.9
      Hz, first trial; 19.9 +/- 1.4 Hz, fifth trial). An exposure to moderate hypoxia
      (approximately 80 Torr) before the repetitive anoxia stimuli produced
      catecholamine levels comparable to those obtained during repetitive anoxia, but
      peak nerve activity was significantly less (22.5 +/- 3.4 vs. 12.7 +/- 2.1 Hz).
      Pretreatment with reserpine (1 mg/100 g) resulted in a large reduction in the
      average hypoxia-induced catecholamine response (1.4 +/- 0.3 microM, n = 9), but
      peak nerve activity was not different from nontreated controls. These results
      demonstrate an independence between carotid body catecholamine secretion and
      nerve activity, suggesting that nerve excitation is, at least, partially mediated
      through pathways independent of granule secretion.

PMID- 8872632
TI  - Adaptive responses of hypertrophying skeletal muscle to endurance training.
AB  - We determined the effects of 6 wk of endurance running on citrate synthase (CS)
      activity and myosin heavy chain (MHC) expression in bilateral surgical-overloaded
      rodent fast-twitch plantaris and slow-twitch soleus muscles. The overload induced
      significant hypertrophy in both muscle types, and this response was enhanced by
      endurance training. The overload-induced compensatory hypertrophy was accompanied
      by a proportional increase in muscle CS content. Although endurance training
      produced significant increases in CS concentration in either muscle type of the
      normal-trained groups (P < 0.05), it was not effective in causing similar changes
      in the overloaded trained muscles. Also, overload of either the sedentary or
      trained groups produced an increase in slower MHC isoforms (i.e., type I in the
      soleus and types I and IIa in the plantaris) and a concomitant decrease in the
      faster MHC isoforms (type IIa in the soleus and IIb in the plantaris; P < 0.05),
      whereas endurance training alone produced the opposite effect, especially in the
      plantaris. Collectively, these data suggest that 1) increments in muscle
      oxidative enzyme content due to endurance training are compromised when a
      hypertrophying process is occurring concomitantly; and 2) the relative loading
      state imposed on the muscle during repetitive locomotor activity is critical in
      regulating the pattern of MHC plasticity.

PMID- 8872633
TI  - Role of neutral endopeptidase in exercise-induced bronchoconstriction in
      asthmatic subjects.
AB  - The membrane-bound metalloproteinase, neutral endopeptidase (NEP), is a degrading
      enzyme of both bronchoconstrictor and bronchodilator peptides within the airways.
      To examine the role of NEP in exercise-induced bronchoconstriction (EIB) in
      asthmatic subjects, we used inhaled thiorphan, a NEP inhibitor, as pretreatment
      to a 6-min standardized exercise challenge. Thirteen clinically stable asthmatic
      subjects participated in this double-blind, placebo-controlled, crossover study
      that was performed on 2 days separated by 48 h. Thiorphan was administered by two
      inhalations of 0.5 ml containing 1.25 mg/ml. Subsequently, exercise was performed
      on a bicycle ergometer at 40-50% of predicted maximal voluntary ventilation while
      inhaling dry air (20 degrees C, relative humidity 6%). The airway response to
      exercise was measured by forced expiratory volume in 1 s (FEV1) every 3 min, up
      to 30 min postexercise challenge, and was expressed both as the maximal percent
      fall in FEV1 from baseline and as the area under the time-response curve (AUC) (0
      30 min). The acute effects of both pretreatments on baseline FEV1 were not
      different (P > 0.2), neither was there any difference in maximal percent fall in
      FEV1 between thiorphan and placebo (P > 0.7). However, compared with placebo,
      thiorphan reduced the AUC by, on average, 26% [AUC (0-30 min, +/-SE): 213.6 +/-
      47.7 (thiorphan) and 288.6 +/- 46.0%fall.h (placebo); P = 0.047]. These data
      indicate that NEP inhibition by thiorphan reduces EIB during the recovery period.
      This suggests that bronchodilator NEP substrates, such as vasoactive intestinal
      polypeptide or atrial natriuretic peptide, modulate EIB in patients with asthma.

PMID- 8872634
TI  - Effects of fatiguing stimulation on intracellular Na+ and K+ in frog skeletal
      muscle.
AB  - The purpose of this study was to describe the alterations in the intracellular
      concentrations of sodium ([Na+]i) and potassium ([K+]i) and the membrane
      potential (Em) as a result of fatiguing stimulation of the frog semitendinosus
      muscle and to relate these changes to the alterations in the sarcolemma action
      potential and force-generating ability of the muscle. [Na+]i and [K+]i were
      measured by using ion-selective microelectrodes. Before stimulation (100-ms
      trains at 150 Hz, 1 stimulus/s for 5 min), [Na+]i, [K+]i, and Em were 16 +/- 1
      mM, 142 +/- 5 mM, and -83 +/- 1 mV, respectively. As a result of stimulation,
      [Na+]i rose to 49 +/- 6 mM and recovered to 16 +/- 2 mM with a time constant
      (tau) of 70 s.[K+]i fell to 97 +/- 8 mM as a result of stimulation, then
      recovered to 148 +/- 5 mM with tau = 56 s. Em depolarized to -74 +/- 3 mV then
      recovered to -83 +/- 2 mV with tau = 53 s. The Na+/K+ permeability ratio of the
      resting membrane fell 3%, whereas at the peak of the action potential the
      permeability ratio fell 38%. A previous study using the same muscle and
      stimulation protocol showed force to recover with a fast initial phase
      (approximately 2 min) and a much slower second phase (approximately 50 min). The
      recovery of [Na+]i, [K+]i, and Em was similar to the fast phase of force
      recovery; thus the altered Na+ and K+ concentration gradient across the
      sarcolemma and t-tubular membrane may contribute to this component of fatigue.
      The possible fatigue mechanisms induced by the altered ionic gradients include 1)
      complete block of the action potential propagation; 2) depolarization-induced
      inactivation of t-tubular charge movement; and 3) a reduced magnitude of the t
      tubular charge due to the lower action potential spike potential.

PMID- 8872635
TI  - Maximal exercise performance after adaptation to microgravity.
AB  - The cardiovascular system appears to adapt well to microgravity but is
      compromised on reestablishment of gravitational forces leading to orthostatic
      intolerance and a reduction in work capacity. However, maximal systemic oxygen
      uptake (Vo2) and transport, which may be viewed as a measure of the functional
      integrity of the cardiovascular system and its regulatory mechanisms, has not
      been systematically measured in space or immediately after return to Earth after
      spaceflight. We studied six astronauts (4 men and 2 women, age 35-50 yr) before,
      during, and immediately after 9 or 14 days of microgravity on two Spacelab Life
      Sciences flights (SLS-1 and SLS-2). Peak Vo2 (Vo2peak) was measured with an
      incremental protocol on a cycle ergometer after prolonged submaximal exercise at
      30 and 60% of Vo2peak. We measured gas fractions by mass spectrometer and
      ventilation via turbine flowmeter for the calculation of breath-by-breath Vo2,
      heart rate via electrocardiogram, and cardiac output (Qc) via carbon dioxide
      rebreathing. Peak power and Vo2 were well maintained during spaceflight and not
      significantly different compared with 2 wk preflight. Vo2peak was reduced by 22%
      immediately postflight (P < 0.05), entirely because of a decrease in peak stroke
      volume and Qc. Peak heart rate, blood pressure, and systemic arteriovenous oxygen
      difference were unchanged. We conclude that systemic Vo2peak is well maintained
      in the absence of gravity for 9-14 days but is significantly reduced immediately
      on return to Earth, most likely because of reduced intravascular blood volume,
      stroke volume, and Qc.

PMID- 8872636
TI  - Determination of regional pulmonary blood flow with systemically injected
      nonentrapped microspheres.
AB  - Radioactive microspheres (MS) injected into the systemic circulation shunt to the
      venous side of the circulation and are trapped in the lung vasculature. We
      hypothesized that regional pulmonary perfusion could be determined by using
      systemically injected shunted MS. In seven anesthetized mechanically ventilated
      foxhounds, regional pulmonary perfusion was measured at baseline and during
      experimental acute respiratory distress syndrome with MS injected into both the
      right and left atrium (protocol 1). Methodological error of the MS technique was
      assessed by simultaneous injection of two different batches of MS into the right
      atrium (protocol 2). Measurement of perfusion during baseline and during
      experimental acute respiratory distress syndrome with shunted MS had a mean bias
      of 0.8 and 5.6% and mean precision of 19.2 and 34.7% (r = 0.94 and r = 0.95),
      respectively, compared with data from nonshunted MS. Simultaneous perfusion
      measurements displayed bias of -2.7 and 6% and precision of 8.2 and 5.3% (r =
      0.98 and r = 0.99), respectively. Systemic shunt should be high for this method
      to prevent bronchial circulation from imposing significant error. We conclude
      that systemically injected MS can be used for simultaneous measurement of
      regional systemic and regional pulmonary perfusion, provided that MS that shunted
      in the first pass are measured in lung tissue.

PMID- 8872637
TI  - Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase,
      in severe hemorrhagic shock.
AB  - We characterized the response to intravenous S-isopropyl isothiourea (IPTU), a
      novel potent nitric oxide synthase (NOS) inhibitor, in rodent and porcine models
      of hemorrhagic shock (HS). IPTU (at 300 micrograms/kg, administered as 3
      subsequent bolus injections), in anesthetized rats hemorrhaged to a mean arterial
      blood pressure (MAP) of 35 mmHg, increased MAP and improved survival over 120
      min. In anesthetized pigs hemorrhaged to a MAP of 45 mmHg, IPTU (0.3 mg/kg plus 1
      mg.kg-1.h-1) increased MAP and systemic vascular resistance. IPTU did not alter
      the cardiac index, renal blood flow, arterial and portal oxygen content, or
      splanchnic oxygen consumption or extraction. In contrast, infusion of
      norepinephrine (100 micrograms.kg-1.h-1) did not alter MAP and increased
      mortality in the rat model, whereas it caused a transient increase in MAP and a
      tachycardia in the porcine model of HS without significantly affecting the other
      parameters studied. Inhibition of the endothelial NOS in early severe HS may have
      beneficial effects on blood pressure and survival without altering cardiac output
      and splanchnic and renal perfusion.

PMID- 8872638
TI  - Modified control of breathing in genetically obese (ob/ob) mice.
AB  - Attenuated hypercapnic chemosensitivity and hypoventilation are characteristics
      periodically associated with human obesity. We tested the hypothesis that
      ventilatory control is altered by genetic determinants and age-dependent factors
      that influence the obese phenotype. To this end, the magnitude and pattern of
      breathing were examined before and associated with the development of obesity in
      C57BL/6J mice homozygous and heterozygous at the ob gene locus. Breathing
      frequency and tidal volume were measured using whole body plethysmography, and
      minute ventilation was assessed during acute hypoxic and hypercapnic challenges
      with intermittent room air exposures. In age- and weight-matched mice before
      pronounced obesity, significant (P < 0.05) reductions in hypercapnic ventilatory
      sensitivity occurred in mutant (ob/ob) mice relative to wild-type (+/+)
      homozygotes primarily because of an attenuated tidal volume. Longitudinal studies
      indicated that mutant ob mice developed rapid baseline breathing relative to the
      wild type, accompanying a twofold greater increase in body mass. Early
      differences between homozygotes in hypercapnic ventilatory sensitivity were
      maintained through 230 days. These data demonstrate that genetic determinants at
      or closely linked to the ob locus influence hypercapnic ventilation before the
      emergence of pronounced obesity, whereas changes in baseline breathing appear due
      to age-dependent increases in body weight.

PMID- 8872639
TI  - Passive tension in rat hindlimb during suspension unloading and recovery:
      muscle/joint contributions.
AB  - Muscle/joint stiffness associated with disuse conditions or weightlessness may
      seriously impair movement and work capacity. The purposes of this study were 1)
      to develop a noninvasive model to measure rat hindlimb passive tension, 2) to
      describe changes in passive tension (i.e., flexibility) during whole body
      suspension and weight-bearing recovery, and 3) to determine relative
      contributions of the posterior hindlimb to passive tension. Male Sprague-Dawley
      rats were suspended (14 days) and reloaded (14 days). On days 0, 7, 14, 17, 21,
      and 28, animals were anesthetized and hindlimb passive tension was measured
      during ankle dorsiflexion. Seven days of suspension significantly increased
      passive tension. Recovery of passive tension occurred by 14 days of weight
      bearing. In suspended animals, increased passive tension was due to
      musculotendinous units (75%) rather than to the joint (25%). Increased passive
      tension did not appear to be due to a shorter muscle, but changes in muscle
      architecture, cytoskeletal proteins, or viscoelastic properties of the muscle and
      its connective tissue elements cannot be excluded.

PMID- 8872640
TI  - Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat
      skeletal muscle fibers.
AB  - Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low
      levels in resting muscles and at substantially higher levels in exercising
      muscles. Increased respiratory activity with exercise leads to O2- production by
      the NADPH oxidase reaction and the subsequent generation of H2O2 from O2- by
      spontaneous dismutation or by the superoxide dismutase reaction. The long-lasting
      (24-h) depression of contractile function after exercise has been linked to
      damage of one or more proteins important in the excitation-contraction coupling
      process. We studied mechanically and chemically skinned fibers from the extensor
      digitorum longus muscle of the rat to evaluate the effects of a 5-min exposure to
      1.0 mM H2O2 on muscle function. We found that H2O2 had no effect on the isometric
      force-producing properties of the contractile apparatus or on Ca2+ uptake by the
      sarcoplasmic reticulum. It did, however, significantly affect Ca2+ release from
      the sarcoplasmic reticulum. Maximum depolarization-induced Ca2+ release was
      inhibited, and the sensitivity to depolarization was decreased. Ca(2+)-induced
      release was completely blocked. We conclude that elevated levels of H2O2 with
      exercise are capable of damaging one or more proteins of the excitation
      contraction coupling process to produce a disruption in function that can
      account, at least in part, for the long-lasting effects of fatiguing stimulation.

PMID- 8872641
TI  - Peak ventilatory responses during cycling and swimming in pregnant and
      nonpregnant women.
AB  - This study was designed to determine whether pregnancy affects peak O2 uptake
      (VO2peak) during swimming compared with cycling. We studied 11 women at 30-34 wk
      gestation and 8-12 wk postpartum. We measured heart rate (HR), O2 uptake (VO2),
      CO2 output (VCO2), minute ventilation (VE), and lactic acid concentration. Peak
      HR was not significantly affected by the type of exercise or by pregnancy.
      VO2peak was 9% lower during swimming than during cycling but was not affected by
      pregnancy, with values for pregnancy cycling, pregnancy swimming, postpartum
      cycling, and postpartum swimming of 2.36 +/- 0.12, 2.11 +/- 0.11, 2.29 +/- 0.10,
      and 2.12 +/- 0.07 l/min, respectively. Peak VCO2 (VCO2peak) and peak VE were
      significantly lower during swimming than during cycling by 18-25%, but only
      VCO2peak during swimming was affected by pregnancy (-10%). Lactic acid
      concentrations were 12-17% lower after swimming than after cycling and 17-31%
      lower during pregnancy than postpartum. We conclude that perceived maximal
      exertion is reached at a lower percent maximal VO2 in swimming than in cycling
      and that the reduced energy expenditure is reflected by lower VO2peak, VCO2peak,
      and peak VE. Pregnancy, however, does not affect VO2peak in cycling or swimming.

PMID- 8872642
TI  - Role of aerobic capacity and body mass index in the age-associated decline in
      heart rate variability.
AB  - The extent to which age-associated changes in aerobic capacity and body
      composition modulate the age-associated decline in heart rate variability (HRV)
      is unknown. We therefore measured HRV, peak O2 consumption (VO2peak) during
      treadmill testing, and relative weight (body mass index; BMI) in 164 healthy
      normotensive adults (75 men, age 20-87 yr) from the Baltimore Longitudinal Study
      on Aging. Two components of HRV, respiratory sinus arrhythmia (RSA; 0.12-0.40 Hz)
      and 0.10-Hz variability (0.06-0.10 Hz), were extracted from 8-min
      electrocardiogram recordings in the supine, seated, and standing postures. RSA,
      0.10-Hz variability, and VO2peak varied inversely with age; BMI was unrelated to
      age. Age contributed 15.5-21.1% independent variance to RSA and 13.2-17.3%
      independent variance to 0.10-Hz HRV. VO2peak did not contribute significantly to
      RSA or 0.10-Hz HRV beyond the effect of age in any posture. There were no
      consistent independent contributions of BMI to HRV. Thus, in this population
      based sample, age-associated changes in aerobic capacity and relative body weight
      do not provide the primary explanation for the decline in HRV observed with
      advancing age.

PMID- 8872643
TI  - Diaphragmatic activity during REM sleep in the adult cat.
AB  - Diaphragmatic electromyograms from five adult cats were studied to determine
      whether diaphragmatic activity, like central respiratory activity, increases in
      rapid-eye-movement (REM) sleep. Breaths with inspiratory durations between 250
      and 2,000 ms were analyzed. 1) There was a greater slope of the moving time
      average of diaphragmatic activity in REM than in non-REM (NREM) sleep. These
      greater slopes occurred whether the route of breathing was through the upper
      airways or through an endotracheal tube and may have resulted from early
      recruitment of motor units. 2) Mean diaphragmatic activity was also greater, but
      other variables (peak activity, the area under the curve of diaphragmatic
      activity, mean intratracheal pressures, inspiratory airflow rates, and tidal
      volumes) were not greater in REM than in NREM sleep. 3) Diaphragmatic activity
      was similar in REM sleep and active wakefulness. 4) Across states, slope of the
      moving time average varied with the duration of inspiration: greater slopes were
      associated with shorter breaths. These results are consistent with an increase in
      central respiratory drive in REM sleep that increases the rate of rise of
      diaphragmatic activity.

PMID- 8872644
TI  - Erythropoietin under real and simulated microgravity conditions in humans.
AB  - The aim of this study was to analyze the time course of erythropoietin (EPO)
      during Earth-bound microgravity simulations such as bed rest, isolation and
      confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate
      which factors could contribute to alterations in EPO under real microgravity
      conditions during and after short- (< 10 days) and long-term (> 6 mo)
      spaceflights. During bed rest (24h), no significant changes in EPO could be
      observed. Subjects confined in a diving chamber facility for 60 days showed a
      decrease in EPO. In the recovery period a slight increase was observed, but EPO
      concentrations did not reach the pre-IC control level. In the control period
      before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT
      the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained
      below the control value and were increased after HDT (P < 0.05). After immersion
      (24 h) increased EPO concentrations could be determined (P < 0.05). During a
      short-term spaceflight the astronauts showed in-flight (day 4) decreased and
      unchanged EPO concentrations. During a long-term spaceflight, 24 h after
      recovery, the cosmonaut showed slightly elevated EPO concentration, which
      increased markedly during the following days. It is concluded that 1) HDT (-6
      degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to
      diminished EPO concentrations, 3) EPO regulation in humans during short- and long
      term spaceflights might be different, 4) changes in central blood volume, i.e.,
      central venous pressure, seem to be involved in the modulation of EPO production
      and release under simulated and real microgravity conditions, and 5) the HDT (-6
      degrees) Earth-bound simulation reflects mostly the changes in EPO production and
      release observed under real microgravity conditions in humans.

PMID- 8872645
TI  - Direct measurement of nitric oxide release from vascular endothelial cells.
AB  - A nitric oxide (NO)-selective electrode was used to directly measure NO release
      from isolated rat aortic endothelium and cultured rat aortic endothelial cells
      (RAECs). Basal release of NO was significantly attenuated by a NO synthase
      inhibitor NG-nitro-L-arginine methyl ester (1 mM) to 42 +/- 14 pmol/1 x 10(5)
      cells (P < 0.01). The basal release of NO was also significantly inhibited by a
      calmodulin antagonist W-7 at 15 microM (P < 0.01). L-Arginine (1 mM),
      significantly stimulated NO release (P < 0.05 vs. control basal release).
      Stimulation of cultured RAECs with two endothelium-dependent vasodilators,
      acetylcholine (100 nM) and A-23187 (1 microM), significantly increased NO release
      [574 +/- 112 pmol/1 x 10(5) cells (n = 5) and 658 +/- 119 pmol/1 x 10(5) cells (n
      = 5) in acetylcholine- and A-23187-stimulated RAECs, respectively]. Basal release
      of NO was also detectable in isolated rat aortic rings with intact endothelium.
      NO release was significantly attenuated by NG-nitro-L-arginine methyl ester and
      augmented by human superoxide dismutase. These data indicate the physiological
      usefulness of the amperometric measurement of NO employing a NO-specific
      electrode in biological systems.

PMID- 8872646
TI  - Effect of exercise training on skeletal muscle histology and metabolism in
      peripheral arterial disease.
AB  - Patients with symptomatic peripheral arterial occlusive disease have a
      claudication-limited peak exercise performance that is improved with exercise
      training. The effects of training on skeletal muscle metabolism were evaluated in
      26 patients with claudication, randomized into a 12-wk program of treadmill
      training (enhances muscle metabolic activity in normal subjects), strength
      training (stimulates muscle hypertrophy in normal subjects), or a nonexercising
      control group. Gastrocnemius muscle biopsies were performed at rest and before
      and after training. After 12 wk, only treadmill training improved peak exercise
      performance and peak oxygen consumption. Treadmill training did not alter type I
      or type II fiber area and did not increase citrate synthase activity but was
      associated with an increase in the percentage of denervated fibers (from 7.6 +/-
      5.4 to 15.6 +/- 7.5%, P < 0.05). Improvement in exercise performance with
      treadmill training was associated with a correlative decrease in the plasma (r = 
      0.67) and muscle (r = -0.59) short-chain acylcarnitine concentrations
      (intermediates of oxidative metabolism). Patients in the strength and control
      groups had no changes in muscle histology or carnitine metabolism, but strength
      trained subjects had a decrease in citrate synthase activity. Thus treadmill
      training increased peak exercise performance, but this benefit was associated
      with skeletal muscle denervation and the absence of a "classic" mitochondrial
      training response (increase in citrate synthase activity). The present study
      confirms the relationship between skeletal muscle acylcarnitine content and
      function in peripheral arterial occlusive disease, demonstrating that the
      response to treadmill training was associated with parallel improvements in
      intermediary metabolism.

PMID- 8872647
TI  - Transcription of the rat skeletal muscle hexokinase II gene is increased by acute
      exercise.
AB  - A single bout of acute exercise increases hexokinase (HK) II mRNA and enzyme
      activity [R. M. O'Doherty, D. P. Bracy, H. Osawa, D. H. Wasserman, and D. K.
      Granner. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E171-E178, 1994]. The
      present study addresses the mechanism of the increase in HK II mRNA. Male rats
      undertook a single bout of treadmill exercise and were then killed immediately or
      after a predetermined recovery period. The gastrocnemius/plantaris muscle
      complex, composed of mixed fiber types, was excised; the nuclei were isolated;
      and HK I, HK II, beta-actin, and alpha-tubulin gene transcription rates were
      measured. Genomic DNA and plasmid DNA were used as positive and negative
      controls, respectively. Immediately after the cessation of 30, 45, or 90 min of
      exercise, HK II gene transcription rates were 1.3 +/- 0.3-,2.9 +/- 0.3-, and 4.0
      +/- 0.6-fold, respectively, above those of sedentary controls. The increases
      after 45 and 90 min of exercise were statistically significant (P < 0.01). One
      hour after the cessation of 30 min of exercise, HK II gene transcription was
      significantly increased (1.40 +/- 0.03-fold; P < 0.05). At all time points,
      transcription of the HK I, beta-actin, and alpha-tubulin genes was unchanged. We
      conclude that the exercise-induced increase in HK II gene transcription appears
      to play a major role in the increase of HK II mRNA and activity.

PMID- 8872648
TI  - Bloodborne markers in humans during multiday exposure to ozone.
AB  - Intermittent exposure of the human lung to ambient levels of ozone (O3) was
      assayed in systemic fluids by using serum alpha-tocopherol (ST) as a gauge of
      oxidative stress and the blastogenic activity of peripheral blood monocytes as an
      index of immune function. Healthy men (n = 10) were evaluated over 3 consecutive
      days (130 min/day) of chamber exposure to O3 and filtered air (FA); subjects
      alternated between rest and light treadmill exercise during exposures. For O3,
      the level was varied at 20-min intervals, i.e., 250, 350, 450, 450, 350, and 250
      parts/billion, and concluded with 10 min at 250 parts/billion. ST was quantitated
      by high-performance liquid chromatography techniques, and T-lymphocyte
      blastogenesis was measured in cell cultures of peripheral blood monocytes by
      comparing [3H]thymidine incorporation in mitogen-stimulated (concanavalin A) and
      nonstimulated cells. After the third day of O3 at 20 h postexposure, ST levels
      were reduced significantly compared with the FA control subjects (down 14%; -0.96
      mumol/l). Mitogen-activated T lymphocytes exhibited a 61% increase in blastogenic
      activity after 3 days of O3 exposure, significant compared with the proliferative
      activity of activated T lymphocytes collected after FA or before O3. Acute airway
      function was impaired by O3, e.g., on day 1, the forced vital capacity and forced
      expiratory volume in 1 s were decreased 8% (-0.92 liter) and 14% (-0.86 l/s),
      respectively, from preexposure values, and full recovery was delayed beyond 24 h.
      Effects of O3 exposure on cellular and biochemical markers increased in magnitude
      after each exposure and did not parallel the apparent adaptability of bronchial
      sensitivity to O3.

PMID- 8872649
TI  - Carbohydrate ingestion and single muscle fiber glycogen metabolism during
      prolonged running in men.
AB  - The aim of this study was to examine the effect of carbohydrate (CHO) ingestion
      on glycogen degradation in type I and type II muscle fibers during prolonged
      running by using a quantitative biochemical method. To this end, eight male
      subjects ran at 70% maximal oxygen uptake to exhaustion on a motorized treadmill
      on two occasions, 1 wk apart. On each occasion, the subjects ingested 8 ml/kg
      body wt of either placebo (Pl) or a 5.5% CHO-electrolyte solution (CHO-E)
      immediately before the start of the run and 2 ml/kg body wt every 20 min
      thereafter. Needle biopsy samples were obtained from the vastus lateralis muscle
      before and after each trial and also at the time coinciding with Pl exhaustion in
      the CHO-E trial. Running time to exhaustion was longer (P < 0.01) in the CHO-E
      trial compared with the Pl trial (132.4 +/- 12.3 and 104.3 +/- 8.6 min,
      respectively). A 25% reduction in glycogen utilization in type I fibers only was
      observed in the CHO-E trial compared with the Pl trial (215.2 +/- 27.5 vs. 285.4
      +/- 30.1 mmol/kg dry wt; P < 0.01). Furthermore, in the CHO-E trial, in contrast
      to the Pl trial, both muscle ATP and phosphocreatine concentrations were well
      maintained throughout exercise. Therefore, because in both the Pl and CHO-E
      trials the type I fibers were glycogen depleted at the point of exhaustion (31.6
      +/- 10.3 and 28.1 +/- 7.1 mmol/kg dry wt, respectively), it is proposed that CHO
      ingestion improved endurance capacity by contributing to oxidative ATP production
      specifically in type I fibers and by doing so delayed the development of glycogen
      depletion in this fiber type.

PMID- 8872650
TI  - Bronchial vascular reabsorption of low-protein interstitial edema liquid in
      perfused sheep lungs.
AB  - Previously, we quantified reabsorption of interstitial pulmonary edema liquid
      into the pulmonary circulation during recovery from hydrostatic edema. To
      determine whether the bronchial circulation also reabsorbs edema liquid, we
      induced very-low-protein interstitial edema in seven sheep lungs by perfusion of
      the pulmonary circulation with diluted blood and 1% albumin in Krebs-Henseleit
      buffer containing 125I-labeled albumin for 70 +/- 40 min. In eight control sheep
      we perfused the lungs with diluted blood and 5% albumin in Krebs-Henseleit buffer
      containing 125I-albumin without causing significant edema formation.
      Subsequently, we washed the intravascular tracer from the pulmonary circulation
      with buffered saline and then perfused the bronchial vessels via the
      bronchoesophageal artery with whole or diluted blood (normal protein osmotic
      pressure). We measured flow, hematocrit, and 125I-albumin concentration in the
      venous outflow into the left atrium and into the azygos vein for 2 h. We
      calculated the volume of liquid reabsorbed on the basis of the change in
      hematocrit and 12I-albumin concentration in the outflow. On the basis of
      hematocrit dilution, the net clearance of interstitial liquid (edema minus
      control) averaged 21 ml (15% of the induced edema). One the basis of 125I-albumin
      reabsorption, the net clearance of interstitial liquid was 12 ml. We conclude
      that the bronchial circulation may be a clearance route for interstitial liquid
      and protein during recovery from low-protein hydrostatic edema.

PMID- 8872651
TI  - Angiotensin receptor 1 blockade does not prevent physiological cardiac
      hypertrophy in the adult rat.
AB  - The renin-angiotensin system has been implicated in the hypertrophic adaptation
      of the heart to exogenous pathological loads, such as hypertension and aortic
      stenosis; however, the role of this hormonal system in the cardiac adaptations to
      physiological loads, such as chronic exercise conditioning, has not been
      established. We therefore studied the effect of angiotensin receptor 1 (AT1)
      blockade on the chronic cardiac responses of rats subjected to an 8-wk swimming
      program. Compared with matched sedentary controls, untreated swimmers increased
      their left ventricular weights by 13%, and swimmers treated with the AT1
      antagonist L-158809 increased their left ventricular weights by 11% (both P <
      0.05 vs. sedentary controls). The incorporation of labeled amino acids into the
      heart at the time of death was unchanged in all groups, and therefore the
      increase in heart weight in both swim-conditioned groups appeared to reflect a
      decrease in the rate of protein degradation in the heart. Hearts from both swim
      conditioned groups manifested an increase in the V1-predominant myosin isoform
      pattern but not an increase in atrial natriuretic factor mRNA expression or
      protein kinase C translocation. The fact that these patterns of adaptation are
      preserved in exercised conditioned animals treated with an AT1 antagonist
      suggests that the chronic hypertrophic response of the heart to physiological
      loads is not influenced by the renin-angiotensin system.

PMID- 8872652
TI  - Endurance exercise with and without a thermal clamp: effects on leukocytes and
      leukocyte subsets.
AB  - To test how leukocyte responses to endurance exercise were modified by clamping
      body temperature, nine men (27.3 +/- 6.0 yr) completed four 80-min immersions to
      midchest at water temperatures of 23 or 39 degrees C; two tests included 40-min
      of cycle ergometer exercise at 65% of aerobic power. When the subjects were
      exercising, rectal temperature peaked at 39.1 +/- 0.4 degrees C in the warm water
      and 37.8 +/- 0.3 degrees C in the cool water. When the subjects were sitting in
      warm water, rectal temperature closely matched the core temperature during
      exercise in cool water, whereas when they were sitting in cool water, rectal
      temperatures decreased to 36.4 +/- 0.6 degrees C. Total and differential white
      cell counts were determined by using a Coulter counter, and cortisol and growth
      hormone concentrations were determined by radioimmunoassay; all data were
      adjusted for changes of blood and plasma volumes. Heat clamping during exercise
      substantially reduced the rise in white cell, lymphocyte, and granulocyte counts
      but not the increase in monocyte count. Clamping also abolished previously
      observed associations between cell counts and cortisol and weakened associations
      with growth hormone concentrations (D. A. McCarthy and M. M. Dale. Sports Med. 6:
      333-363, 1988). We conclude that both exercise and a rise of core temperature
      contribute to the changes in white cell and subset counts during and immediately
      after moderate exercise. Both cortisol and growth hormone concentrations appear
      to be mediators of these responses.

PMID- 8872653
TI  - Alveolar liquid clearance is increased by endogenous catecholamines in
      hemorrhagic shock in rats.
AB  - The primary objective of this study was to test the hypothesis that hemorrhagic
      shock would stimulate alveolar liquid clearance by a catecholamine-dependent
      mechanism. Anesthetized rats were hemorrhaged to a mean arterial pressure of 30
      mmHg for 90 min, but they were not resuscitated. Alveolar liquid clearance was
      measured by the concentration of labeled and unlabeled protein over 2 h in an
      isosmolar physiological solution of 5% albumin that had been instilled into one
      lung. Hemorrhaged rats developed a severe metabolic acidosis that was associated
      with a 5- to 10-fold rise in plasma epinephrine levels. There was a 60% increase
      in alveolar liquid clearance in the hemorrhaged rats compared with control rats
      (55 +/- 6 vs. 34 +/- 7%; P < 0.05). Amiloride (10(-4) M) or propranolol (10(-4)M)
      inhibited the increase in alveolar liquid clearance. Thus the endogenous release
      of catecholamines associated with hemorrhagic shock markedly stimulates alveolar
      fluid clearance by a beta-adrenergic-mediated stimulation of active sodium
      transport. These data suggest a new, previously unrecognized mechanism that may
      protect against alveolar flooding in the acute phase of hemorrhagic shock.

PMID- 8872654
TI  - Effect of skin temperature on multifrequency bioelectrical impedance analysis.
AB  - This study assessed the effects of changes in skin temperature on multifrequency
      bioimpedance analysis (MF-BIA) and on the prediction of body water compartments.
      Skin temperature (baseline 29.3 +/- 2.1 degrees C) of six healthy adults was
      raised over 50 min to 35.8 +/- 0.6 degrees C, followed by cooling for 20 min to
      26.9 +/- 1.3 degrees C, by using an external heating and cooling blanket. MF-BIA
      was measured at both distal (conventional) and proximal electrode placements.
      Both distal and proximal impedance varied inversely with a change in skin
      temperature across all frequencies (5-500 kHz). The change in proximal impedance
      per degree centigrade change in skin surface temperature was approximately 60% of
      distal impedance. The change in measured impedance at 50 kHz erroneously
      increased predicted total body water (TBW) by 2.6 +/- 0.9 liters (P < 0.001) and
      underpredicted fat mass by 3.3 +/- 1.3 kg (P < 0.0001). Computer modeling of the
      MF-BIA data indicated changes in predicted water compartments with temperature
      modifications; however, the ratio of extracellular water (ECW) to TBW did not
      significantly change (P < 0.4). This change in impedance was not due to a change
      in the movement of water of the ECW compartment and thus probably represents a
      change in cutaneous impedance of the skin. Controlled ambient and skin
      temperatures should be included in the standardization of BIA measurements. The
      error in predicted TBW is < 1% within an ambient temperature range of 22.3 to
      27.7 degrees C (72.1-81.9 degrees F).

PMID- 8872655
TI  - Shift working in the Chilean Andes (> 3,600 m) and its influence on
      erythropoietin and the low-pressure system.
AB  - It was hypothesized that, in shift workers with a history of intermittent hypoxic
      stress (working 10 days at > 3,600 m, then resting for 4 days at sea level) for >
      5 yr, the initial erythropoietin (EPO) response and the changes in central venous
      pressure (CVP) are different from those in Caucasian lowlanders. We studied the
      kitchen personnel (n = 11) of a mine (3,600 m) and a group of Caucasian
      lowlanders (n = 5). Blood samples were taken, and CVP was determined several
      times before, during, and after a typical shift. At baseline data collection
      (BDC) before transition, the shift workers had EPO concentrations of 5.2 +/- 2.4
      mU/ml, which increased at altitude (P < 0.01) and returned to BDC values on the
      recovery (day 16). The Caucasians showed the same time course. Serum transferrin
      receptor concentrations did not change in either group. CVP values were generally
      higher in the shift workers than in the Caucasians. In conclusion, the hypothesis
      that the initial EPO response to a hypoxic stimulus is altered in these shift
      workers has to be refuted. Higher hemoglobin concentrations and/or CVP values in
      shift workers might be responsible for the rather low EPO concentrations in shift
      workers at BDC.

PMID- 8872656
TI  - Preexercise glucose ingestion and glucose kinetics during exercise.
AB  - The present study was undertaken to examine the effects of glucose ingestion
      before exercise on liver glucose output and muscle glucose uptake during
      exercise. On two occasions, at least 1 wk apart, six trained men (peak pulmonary
      O2 uptake = 5.11 +/- 0.17 l/min) ingested 400 ml of a solution containing either
      75 g glucose [carbohydrate (CHO)] or a sweet placebo [control (Con)] 30 min
      before 60 min of exercise at 71 +/- 1% peak pulmonary O2 uptake. Glucose kinetics
      (rates of appearance and disappearance) were measured by a primed continuous
      infusion of [6,6-2H2]glucose. Liver glucose output was derived from total glucose
      appearance and the appearance of ingested glucose from the gut. After glucose
      ingestion, plasma glucose increased to 6.4 +/- 0.4 mmol/l immediately before
      exercise, fell to 4.2 +/- 0.5 mmol/l after 20 min of exercise, and then increased
      to a higher value than in the Con group (5.4 +/- 0.3 vs. 4.7 +/- 0.1 mmol/l; P <
      0.05) after 60 min of exercise. In the CHO group, plasma insulin was higher
      immediately before exercise (P < 0.05) and, despite falling during exercise,
      remained higher than in the Con group after 60 min of exercise (57.0 +/- 11.4 vs.
      24.8 +/- 1.7 pmol/l; P < 0.05). The rapid fall in plasma glucose in the CHO group
      was the result of a higher muscle glucose uptake with the onset of exercise (P <
      0.05), which could not be matched by the glucose rate of appearance. Liver
      glucose output was decreased by glucose ingestion, and although it increased
      during the early stages of exercise in the CHO group, it did not rise above the
      basal values and was reduced by 62% over the 60 min of exercise compared with the
      Con group. In summary, preexercise glucose ingestion results in increased muscle
      glucose uptake and reduced liver glucose output during exercise.

PMID- 8872657
TI  - Sarcomere relaxation in hamster diaphragm muscle.
AB  - We characterized instantaneous sarcomere relaxation over the load continuum in
      isolated hamster diaphragm muscles by means of laser diffraction. In afterloaded
      twitches, sarcomere relaxation displayed two consecutive phases. The bulk of
      sarcomere lengthening occurred during the first phase and corresponded in time to
      muscle lengthening. The second phase of sarcomere relaxation was slower and
      corresponded in time to tension decay. At initial muscle length, the peak
      velocity of sarcomere lengthening (SVL) was linearly related to both the maximum
      extent of sarcomere shortening (delta SL) and sarcomere length at peak shortening
      (SLmin; each P < 0.01). Varying preload modified the SVL vs. SLmin relationship
      but not the SVL vs. delta SL relationship. At a given preload, muscle tension
      decay began at a similar sarcomere length, regardless of the afterload level. In
      conclusion, our results support the role played by sarcomere length in regulating
      the diaphragm muscle-lengthening rate but not the rate of tension decline.

PMID- 8872658
TI  - Effects of sustained and repetitive isocapnic hypoxia on ventilation and
      genioglossal and diaphragmatic EMGs.
AB  - We compared the effects of sustained isocapnic hypoxia (SIH; 20 min) and
      repetitive isocapnic hypoxia (RIH; 10 2-min episodes) on ventilation (VI),
      genioglossal (EMGgg) and diaphragmatic electromyographic (EMGdi) activities, and
      supraglottic airway resistance in 11 normal supine male subjects (36.6 +/- 2.2
      yr) during wakefulness. Seven of the subjects had control measurements on a
      separate day. Desaturation was similar (arterial O2 saturation 80-84%) in the SIH
      and RIH protocols. SIH and RIH caused a biphasic ventilatory response: early
      augmentation of VI (169.5 +/- 6.9 and 168.9 +/- 4.3% of baseline, respectively;
      not significant) followed by a significant roll-off (VI after 20 min of
      cumulative hypoxia 153 +/- 4.0 and 150.8 +/- 10.2% respectively; not
      significant). Moving-time-average EMGdi signals (peak inspiratory and phasic)
      demonstrated a similar biphasic response in the two protocols. Mean EMGgg
      responses, however, differed. During SIH, peak inspiratory EMGgg increased early
      and remained elevated. Phasic and tonic EMGgg signals showed a similar trend.
      During RIH, early augmentation of peak inspiratory and phasic EMGgg signals was
      followed by a marked roll-off in activity such that by the 10th hypoxic episode
      neither value increased above baseline. In the 2-min periods between hypoxic
      episodes, there was a progressive suppression of peak inspiratory and phasic
      EMGgg values below baseline. Supraglottic airway resistance did not change
      significantly during either SIH or RIH. VI and phasic EMGs did not change during
      control experiments. We conclude that in awake normal male subjects SIH and RIH
      cause similar biphasic responses in VI and EMGdi activity. Phasic EMGgg activity
      responses differ between SIH and RIH: EMGgg remains augmented during SIH, whereas
      during RIH early augmentation is followed by marked suppression.

PMID- 8872659
TI  - Changes in serum enzyme activities after injection of bupivacaine into rat
      tibialis anterior.
AB  - This study investigated the time course of changes in serum creatine kinase (CK),
      aspartate aminotransferase (AST), and alanine amino-transferase (ALT) activities
      after intramuscular injection of bupivacaine into the tibialis anterior (TA) of
      rats. Morphological changes in muscle cells, relationships between the amount of
      increase in the enzyme activities and the muscle mass damaged, and responses of
      serum enzymes to additional injections of bupivacaine hydrochloride (BPVC) were
      also examined. Adult male Wistar rats (24 wk) were placed into one of four
      groups. Group A (n = 7) was a control, and no injection was applied. Saline
      solution (0.5 ml of 0.9%) was injected into the right TA for group B (n = 5).
      BPVC (0.5 ml of 0.5%) was injected into the right TA for group C (n = 9) and into
      both the right and left TA for group D (n = 9). No increases in CK, AST, and ALT
      were observed for groups A and B. After BPVC injection, groups C and D showed
      significant (P < 0.01) increases in serum enzyme activities. CK peaked 4 h after
      BPVC injection, and AST and ALT peaked 12 h postinjection, then returned to the
      baseline by the time infiltration of mononuclear cells into the damaged muscle
      cells progressed. The amount of enzyme increase was significantly larger (P <
      0.01) for group D compared with group C. Injection of BPVC into the right then
      into the left TA 4 h later displayed a bipolar response, and the second injection
      into the TA 12 wk after the first injection resulted in smaller increase in serum
      enzyme activities. It appeared that increases in serum enzyme activities
      reflected muscle damage; however, changes in enzymes occurred in the early stage
      of myonecrosis.

PMID- 8872660
TI  - Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues:
      theory.
AB  - The hypothesis that the distribution of oxygen demand in relation to oxygen
      supply (dO2/qO2) effects oxygen extraction in peripheral tissues was tested. By
      using a simple theoretical model, realistic biphasic oxygen consumption-delivery
      relationships were predicted from dO2/qO2 distributions. Increasing width
      (relative dispersion) of the dO2/qO2 distribution, indicating mismatch between
      oxygen demand and supply, nonlinearly decreased the critical oxygen extraction
      ratio (calculated by using dual-line regression). Skewed dO2/qO2 distributions
      had a lesser effect. Incomplete oxygen uptake, due to diffusion limitation or
      other causes of physiological arteriovenous shunt, linearly decreased the
      critical oxygen extraction ratio. Approximate dO2/qO2 distributions were then
      estimated from previously reported capillary transit-time distributions. Critical
      oxygen extraction ratios predicted from these estimated dO2/qO2 distributions
      match reported values. This theoretical approach also predicts the decrease in
      the critical oxygen extraction ratio in porcine gut after endotoxin infusion in
      the companion paper (M. F. Humer, P. T. Phang, B. P. Friesen, M. F. Allard, C. M.
      Goddard, and K. R. Walley. J. Appl. Physiol. 81: 895-904, 1996). Much as
      pulmonary ventilation-perfusion relationships account for pulmonary gas exchange,
      dO2/qO2 distributions quantitatively account for measured tissue oxygen
      extraction and predict novel features of the relationship between heterogeneity
      and oxygen extraction.

PMID- 8872661
TI  - Heterogeneity of gut capillary transit times and impaired gut oxygen extraction
      in endotoxemic pigs.
AB  - We tested the hypothesis that endotoxin increases the heterogeneity of gut
      capillary transit times and impairs oxygen extraction. The gut critical oxygen
      extraction ratio was determined by measuring multiple oxygen delivery-consumption
      points during progressive phlebotomy in eight control and eight endotoxin-infused
      anesthetized pigs. In multiple 1- to 2-g samples of small bowel, we measured
      blood volume (radiolabeled red blood cells) and flow (radiolabeled 15-microns
      microspheres) before and after critical oxygen extraction. Red blood cell transit
      time (= volume/flow) multiplied by morphologically determined capillary/total
      blood volume gave capillary transit time. During hemorrhage, capillary/total
      blood volume did not change in the endotoxin group (0.5 +/- 4.5%) but increased
      in the control group (17.6 +/- 2.5%; P < 0.05) due to a decrease in total gut
      blood volume. Flow decreased significantly in the endotoxin group (36 +/- 10%; P
      < 0.05) but not in the control group (12 +/- 10%). Capillary transit-time
      heterogeneity increased in the endotoxin group (12.3 +/- 4.9%) compared with the
      control group (-5.8 +/- 7.4%; P < 0.05), predicting a critical oxygen extraction
      ratio 0.14 lower in the endotoxin group than in the control group (K. R. Walley.
      J. Appl. Physiol. 81: 885-894, 1996). This matches the measured difference
      (endotoxin group, 0.60 +/- 0.04; control group, 0.74 +/- 0.03; P < 0.05).
      Increased heterogeneity of capillary transit times may be an important cause of
      impaired oxygen extraction.

PMID- 8872662
TI  - Effects of ranolazine on oxidative substrate preference in epitrochlearis muscle.
AB  - Ranolazine is an novel investigational antianginal agent that stimulates glucose
      oxidation in isolated rat hearts. This study determined its effects on metabolic
      substrate and O2 utilization in an in vitro skeletal muscle preparation, the rat
      epitrochlearis muscle. Muscles were superfused with Krebs-Henseleit buffer
      containing 3% albumin, 0.4 mM palmitate, 5.5 mM glucose, 0.5 mM lactate, and a
      physiological amino acid mixture. Perfusate also contained either 1) [U
      14C]glucose for measurement of glucose oxidation or 2) [9,10-3H]palmitate and [U
      14C]lactate for measurement of palmitate and lactate oxidation. Addition of
      ranolazine (10 microM) significantly stimulated glucose oxidation and decreased
      palmitate oxidation but had no effect on lactate oxidation. Overall, the
      calculated relative contribution of glucose oxidation to aerobic ATP production
      increased from 12 to 33%, whereas from palmitate it decreased from 55 to 26%.
      Ranolazine did not alter tissue malonyl-CoA contents, making it unlikely that the
      decrease in palmitate oxidation caused by ranolazine is due to a decrease in the
      activity of acetyl-CoA carboxylase. These data demonstrate that ranolazine can
      shift energy substrate preference in skeletal muscle, which could potentially
      prove useful in ischemic disorders of skeletal muscle.

PMID- 8872663
TI  - Pulmonary hemodynamic response to exercise in subjects with prior high-altitude
      pulmonary edema.
AB  - Individuals with a prior history of (susceptible to high altitude pulmonary edema
      (HAPE-S) have high resting pulmonary arterial pressures, but little data are
      available on their vascular response to exercise. We studied the pulmonary
      vascular response to exercise in seven HAPE-S and nine control subjects at sea
      level and at 3,810 m altitude. At each location, both normoxic (inspired PO2 =
      148 Torr) and hypoxic (inspired PO2 = 91 Torr) studies were conducted. Pulmonary
      hemodynamic measurements included pulmonary arterial and pulmonary arterial
      occlusion pressures. A multiple regression analysis demonstrated that the
      pulmonary arterial pressure reactivity to exercise was significantly greater in
      the HAPE-S group. This reactivity was not influenced by altitude or oxygenation,
      implying that the response was intrinsic to the pulmonary circulation. Pulmonary
      arterial occlusion pressure reactivity to exercise was also greater in the HAPE-S
      group, increasing with altitude but independent of oxygenation. These findings
      suggest an augmented flow-dependent pulmonary vasoconstriction and/or a reduced
      vascular cross-sectional area in HAPE-S subjects.

PMID- 8872664
TI  - Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary
      edema.
AB  - Ventilation-perfusion (VA/Q) mismatch has been shown to increase during exercise,
      especially in hypoxia. A possible explanation is subclinical interstitial edema
      due to high pulmonary capillary pressures. We hypothesized that this may be
      pathogenetically similar to high-altitude pulmonary edema (HAPE) so that HAPE
      susceptible people with higher vascular pressures would develop more exercise
      induced VA/Q mismatch. To examine this, seven healthy people with a history of
      HAPE and nine with similar altitude exposure but no HAPE history (control) were
      studied at rest and during exercise at 35, 65, and 85% of maximum 1) at sea level
      and then 2) after 2 days at altitude (3,810 m) breathing both normoxic (inspired
      Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) gas at both locations. We
      measured cardiac output and respiratory and inert gas exchange. In both groups,
      VA/Q mismatch (assessed by log standard deviation of the perfusion distribution)
      increased with exercise. At sea level, log standard deviation of the perfusion
      distribution was slightly higher in the HAPE-susceptible group than in the
      control group during heavy exercise. At altitude, these differences disappeared.
      Because a history of HAPE was associated with greater exercise-induced VA/Q
      mismatch and higher pulmonary capillary pressures, our findings are consistent
      with the hypothesis that exercise-induced mismatch is due to a temporary
      extravascular fluid accumulation.

PMID- 8872665
TI  - In vivo IIX and IIB fiber recruitment in gastrocnemius muscle of the rat is
      compartment related.
AB  - The purpose of the present study was to investigate to what extent fast-twitch
      IIX and IIB fiber recruitment was related to the natural existing muscle
      compartments (subvolumes of muscle innervated by different primary nerve
      branches) in rat medial gastrocnemius. Three groups (n = 6) of rats trotted on a
      motor-driven treadmill (20 degrees incline) at different speeds. A fourth group
      served as controls, and a fifth group received in situ electrical stimulation of
      all medial gastrocnemius muscle fibers. Postexercise glycogen levels (periodic
      acid-Schiff staining intensities) were made. Running caused more and in situ
      stimulation caused less glycogen breakdown in the proximal IIX and IIB fibers
      compared with the fibers of the same type in the most distal compartment.
      Furthermore, the boundaries of the most distal compartment could often be
      recognized in the periodic acid-Schiff-stained cross sections. It was concluded
      that during running the proximal IIX and IIB fibers were recruited to a greater
      extent (and at lower treadmill speeds) compared with the distal IIX and IIB
      fibers, respectively.

PMID- 8872666
TI  - Endothelium-derived nitric oxide activity in forearm vessels of tennis players.
AB  - The aim of this study was to determine whether physical conditioning induced by a
      repetitive exercise stimulus would elicit changes in the response of forearm
      resistance vessels to an infusion of substances that modulate nitric oxide
      synthesis. Forearm blood flow responses to a 5-min ischemic stimulus and
      intrabrachial infusion of acetylcholine, sodium nitroprusside, and NG-monomethyl
      L-arginine were examined in the preferred and nonpreferred limbs of eight
      habitual tennis players. Forearm volume, girth, and grip strength were
      significantly greater in the preferred limb, indicating a bilateral difference in
      physical condition. This was associated with an enhanced reactive hyperemic
      response in the preferred limb (53.5 +/- 9.4 vs. 38.8 +/- 4.7 ml.100 ml-1.min-1;
      P < 0.05). No differences between the limbs were evident in response to
      acetylcholine, sodium nitroprusside, or NG-monomethyl-L-arginine. These results
      suggest that exercise training enhances the peak vasodilator capacity of the
      vasculature without influencing basal or stimulated activity of the nitric oxide
      dilator system in vivo.

PMID- 8872667
TI  - Air hunger induced by acute increase in PCO2 adapts to chronic elevation of PCO2
      in ventilated humans.
AB  - Brief increases in arterial PCO2 (PaCO2) (lasting several minutes) produce a
      sensation of respiratory discomfort (air hunger). It is not known whether air
      hunger adapts to chronic changes in PaCO2. This study tested whether the level of
      end-tidal PCO2 (PETCO2) required to evoke air hunger would increase with chronic
      elevation of PETCO2 (lasting several days). Four ventilator-dependent subjects
      participated in a 2-wk study during which they were ventilated with air (placebo)
      or air rich in CO2 (CO2 exposure). Average resting PETCO2 during control periods
      was 25 Torr (typical for such patients); PETCO2 was 15 Torr higher during CO2
      exposure. Ventilation and arterial PO2 did not differ between conditions.
      Periodically, we performed tests in which subjects rated the intensity of air
      hunger induced by brief increases in PETCO2. The increase in PETCO2 required to
      elicit a given air hunger rating during CO2 exposure also increased by
      approximately 15 Torr. That is, subjects' sensation of air hunger fully adapted
      to the chronic increase in PETCO2. Arterial pH did not fully return to control
      values during CO2 exposure. Accommodation in the chemoreceptors and neural
      pathways that subserve air hunger sensation may explain the adaptation of air
      hunger.

PMID- 8872668
TI  - Multiple-breath washout and washin experiments in steers.
AB  - Multiple-breath N2 washouts (WO) and washins (WI) were performed during regular
      tidal breathing in 11 unsedated healthy steers approaching pulmonary functional
      maturity (mean body weight = 271 kg). They inspired 20% O2 in 80% Ar during the
      WO and air during the WI. For each steer, we computed two indexes of ventilation
      inhomogeneity from the N2 WO curves: 1) the curvilinearity of the logarithm of
      end-tidal N2 concentrations as a function of cumulative expired volume reflected
      in the ratio of two slopes fitted between 100 and 50% and between 50 and 10%,
      respectively, of end-tidal N2 concentration of the first breath of the WO; and 2)
      the N2 phase III slope divided by the mean expired concentration (Sn) of each
      breath also plotted as a function of cumulative expired volume. Equivalent
      computation of both parameters was done on WI and WO curves, and similar results
      were obtained. The mean slope ratio was 0.812 +/- 0.119 (SD) for all the steers,
      which is consistent with topographic gravity-dependent specific ventilation
      distribution inhomogeneity. Sn was independent of the breath number both for WO
      and WI (mean Sn = 0.130 +/- 0.057 liters-1), suggesting that emptying between
      unequally ventilated units, is synchronous. This behavior resembles that observed
      in rats postmortem (S. Verbanck, E.R. Weibel, and M. Paiva. J. Appl Physiol. 71:
      847-854, 1991) but contrasts with experiments in humans, in whom convection
      dependent ventilation inhomogeneities generate a marked increase in Sn throughout
      the entire WO (A. B. H. Crawford, M. Makowska, M. Paiva, and L. A. Engel. J.
      Appl. Physiol. 59: 838-846, 1985). This is surprising because one would expect
      gravity-dependent sequential emptying in animals of this size.

PMID- 8872669
TI  - Lung mechanics during induced bronchoconstriction.
AB  - To elucidate differences in lung mechanics, we investigated the relative changes
      of partial forced expiratory flows at 50 and 30% of vital capacity, pulmonary
      resistance (RL), dynamic elastance (Edyn), and the effects of a deep inhalation
      (DI) on maximal flows, Edyn, and RL in eight asthmatic and eight normal
      individuals during bronchial challenges with methacholine, histamine, and ATP. RL
      was partitioned into inspiratory and expiratory resistance. Different constrictor
      agents did not induce specific patterns of response. For a given decrement of
      flow at 50 and 30% vital capacity, RL increased significantly more in normal than
      in asthmatic individuals. The ratio of inspiratory to expiratory RL was always <
      1 at baseline but became > 1 in the majority of asthmatic and normal individuals
      when RL exceeded 12.2 +/- 0.9 cmH2O.1-1.s, suggesting that tidal inspiration may
      have induced transient bronchodilation in more constricted subjects. In asthmatic
      individuals, DI had a significantly smaller effect on flow but not on RL compared
      with normal individuals. The recovery of RL and Edyn after DI was faster than
      Edyn for both normal and asthmatic individuals. These findings are consistent
      with the idea that asthmatic individuals have a stronger peripheral response to
      agonists than normal individuals.

PMID- 8872670
TI  - Circulatory sequelae of administering CPAP in hyperdynamic sepsis are time
      dependent.
AB  - Evidence questions the circulation's ability to acutely compensate for abrupt
      changes in O2 delivery (Qo2). Because both sepsis and continuous positive airway
      pressure (CPAP) may alter the metabolic regulation of tissue oxygenation, we
      designed an experiment to determine the interaction, if any, between sepsis and
      time on circulatory homeostasis after the application of CPAP. Twenty-four sheep
      were randomized to cecal ligation and perforation (CLP) or sham procedure (Sham)
      and then rerandomized to receive either CPAP (10 mmHg) or no CPAP (No CPAP;
      CLP/CPAP, n = 8; CLP/No CPAP, n = 8; Sham/CPAP, n = 4; Sham/No CPAP, n = 4).
      Forty-eight hours later, CLP animals demonstrated an elevated cardiac index
      (+63%), systemic Qo2 (+49%), and systemic O2 uptake (+28%). Organ blood flow,
      measured with radiolabeled microspheres, was augmented to the heart and depressed
      in organs comprising the splanchnic circulation. Compared with the CLP/No CPAP
      group and both Sham groups, myocardial Qo2 in the CLP/ CPAP group was
      significantly elevated when measured both 2 and 8 h after CPAP. These changes
      were unrelated to differences in mean heart work between the study groups.
      Simultaneously, QO2 to all of the small gut, large gut, pancreas, and kidney in
      the CLP/CPAP group was elevated during the 2-h study yet reverted to levels not
      different from baseline by the 8-h study. These data demonstrate 1) a unique
      sepsis x time interaction with the use of 10 mmHg of CPAP, particularly in the
      "nonvital" circulations, and 2) CPAP effects on the septic coronary circulation,
      which were unexplained by changes in external determinants of myocardial O2 need.

PMID- 8872671
TI  - Oxygen respiratory gas analysis by sine-wave measurement: a theoretical model.
AB  - A sinusoidal forcing function inert-gas-exchange model (C. E. W. Hahn, A. M. S.
      Black, S. A. Barton, and I. Scott. J. Appl. Physiol. 75: 1863-1876, 1993) is
      modified by replacing the inspired inert gas with oxygen, which then behaves
      mathematically in the gas phase as if it were an inert gas. A simple perturbation
      theory is developed that relates the ratios of the amplitudes of the inspired,
      end-expired, and mixed-expired oxygen sine-wave oscillations to the airways' dead
      space volume and lung alveolar volume. These relationships are independent of
      oxygen consumption, the gas-exchange ratio, and the mean fractional inspired
      (FIO2) and expired oxygen partial pressures. The model also predicts that blood
      flow shunt fraction (Qs/QT) is directly related to the oxygen sine-wave amplitude
      perturbations transmitted to end-expired air and arterial and mixed-venous blood
      through two simple equations. When the mean FIO2 is sufficiently high for
      arterial hemoglobin to be fully saturated, oxygen behaves mathematically in the
      blood like a low-solubility inert gas, and the amplitudes of the arterial and end
      expired sine-wave perturbations are directly related to Qs/QT. This relationship
      is independent of the mean arterial and mixed-venous oxygen partial pressures and
      is also free from mixed-venous perturbation effects at high forcing frequencies.
      When arterial blood is not fully saturated, the theory predicts that QS/QT is
      directly related to the ratio of the amplitudes of the induced-saturation
      sinusoids in arterial and mixed-venous blood. The model therefore predicts that
      1) on-line calculation of airway dead space and end-expired lung volume can be
      made by the addition of an oxygen sine-wave perturbation component to the mean
      FIO2; and (2) QS/QT can be measured from the resultant oxygen perturbation sine
      wave amplitudes in the expired gas and in arterial and mixed-venous blood and is
      independent of the mean blood oxygen partial pressure and oxyhemoglobin
      saturation values. These calculations can be updated at the sine-wave forcing
      period, typically 2-4 min.

PMID- 8872672
TI  - Measurement of respiratory parameters by using inspired oxygen sinusoidal forcing
      signals.
AB  - A companion paper (C. E. W. Hahn. J. Appl. Physiol 81: 985-997, 1996) described a
      continuous-flow gas-exchange mathematical model, which predicted that forced
      inspired oxygen sinusoids could be used to measure respiratory parameters
      rapidly, in place of the inert gas argon. We therefore made simultaneous
      measurements of dead space volume (VD) and alveolar volume (VA) in an animal
      model, using argon and oxygen inspired gas concentration sinusoid forcing
      signals, and then compared the results. Our data confirmed the model prediction
      that the attenuations of the oxygen and argon sinusoid perturbations are
      identical in the alveolar gas space, even though there is a net uptake of oxygen
      by the body. Our results show that the calculated values of VD and VA, obtained
      by using inspired oxygen forcing signals, were independent of both the mean
      fractional inspired oxygen concentration (FIO2; range 0.18-0.80% vol/vol) and the
      oxygen forcing signal amplitude (range +/- 2-6% vol/vol). In these studies,
      oxygen forcing signals, with forcing periods between 1 and 2 min, were able to
      measure controlled changes in instrument dead space to within 16 ml and also
      measure positive end-expiratory pressure-induced changes in VA. Under hyperoxic
      conditions, intravascular oxygen sensors confirmed that the sinusoidal PO2 signal
      passed into the arterial blood but not into the mixed-venous blood. However, the
      sinusoid perturbation PO2 signal did pass into the mixed-venous blood when the
      mean FIO2 was mildly hypoxic (FIO2 = 0.18% vol/vol). These data show that oxygen
      can be used instead of argon to measure airways dead space and VA.

PMID- 8872673
TI  - Body plethysmographic measurement of thoracic gas volume without panting against
      a shutter.
AB  - When a subject breathes through a pneumotachograph in a body box, the measured
      value of specific airway resistance (sRaw1) is equal to the product of thoracic
      gas volume (TGV) and the sum of the airway resistance (Raw) and the instrument
      resistance (Rins). If an additional resistance (Radd) is put in the breathing
      path, the measured specific, airway resistance (sRaw2) exceeds sRaw1 by the
      product of TGV and Radd and can be used for determining TGV. With the use of a
      device increasing Rins by a known amount (Radd) during normal breathing, sRaw1
      and sRaw2 were measured in 3 normal subjects, 16 asthmatic patients, 2 patients
      with chronic obstructive pulmonary disease, and 1 patient with restrictive lung
      disease from the slopes of the x-y plots of airflow vs. box signals obtained
      before and after adding Radd. TGV was calculated by dividing (sRaw2-sRaw1) bu
      Radd. We also determined subjects' TGV by the panting method of A. B. DuBois, S.
      Y. Botelho, G. N. Bedell, and J. H. Comroe, Jr. (J. Clin. Invest. 35: 322-326,
      1956) and functional residual capacity by the helium-dilution method. The results
      of the new method were quite reproducible (coefficient of variation = 5.6) and
      equivalent to those obtained by the other two methods.

PMID- 8872674
TI  - Validation of a telemetry system for long-term measurement of blood pressure.
AB  - We have used an implanted telemetry system to continuously monitor blood pressure
      (BP) in three dogs for durations ranging from 28 to 75 wk after implantation.
      Measurements of BP obtained by telemetry were compared every 3-12 wk, with
      measurements of BP recorded with a manometer-tipped catheter that was inserted
      into a femoral artery. Over a wide range of both physiological and
      pharmacologically manipulated pressures (40-200 mmHg), the values of BP obtained
      by the two methods were highly correlated (all r > 0.966; all P < or = 0.0001).
      However, the mean differences between the values obtained by the two systems were
      different from zero (range +29.6 to -1.5 mmHg; P < or = 0.0001), indicating an
      offset in the BP values recorded from the implanted system. Furthermore, this
      offset was dependent on the absolute level of the BP. The findings indicate that,
      for a period of at least 28 wk and up to 75 wk after implantation, the telemetry
      system accurately measures acute changes in BP and can reliably measure absolute
      BP provided that the system is properly validated.

PMID- 8872675
TI  - Daily physical activity assessment: comparison between movement registration and
      doubly labeled water.
AB  - The use of movement registration for daily physical activity assessment was
      evaluated during a 7-day period in 30 free-living subjects. Body movement was
      registered with a Tracmor motion sensor consisting of a triaxial accelerometer
      and a data unit for on-line processing of accelerometer output over 1-min
      intervals. Average Tracmor output was correlated against four different energy
      estimates: 1) average daily metabolic rate (ADMR), determined with doubly labeled
      water; 2) ADMR-sleeping metabolic rate (SMR; determined in a respiration
      chamber); 3) (ADMR-SMR) per kilogram of body mass; and 4) the overall physical
      activity level (PAL = ADMR/SMR). The highest correlation was found for the
      relationship between Tracmor output and PAL (r = 0.58). After correction for
      Tracmor values arising from vibrations produced by transportation means, this
      correlation was improved to 0.73. There was no difference between Tracmor output
      and PAL in discriminating between overall activity levels with "low" (PAL <
      1.60), "moderate" (1.60 < or = PAL < or = 1.85), and "high" (PAL > 1.85)
      intensity. It is concluded that the Tracmor can be used in free-living subjects
      to distinguish among interindividual as well as intraindividual levels of daily
      physical activity.

PMID- 8872676
TI  - Telemetry monitoring of pulmonary arterial pressure in freely moving rats.
AB  - Several rat models of pulmonary hypertension have been developed. However, up
      until now it has been difficult to monitor pulmonary arterial pressure for long
      periods of time. The goal of the present study was to develop a telemetry system
      allowing chronic monitoring of pulmonary arterial pressure in freely moving rats.
      For this purpose, while animals were under anesthesia, a sensing catheter was
      implanted into the pulmonary arterial trunk through the right ventricle. This
      catheter was connected to an emitter implanted in the abdomen. Validation of the
      system was performed in three steps. First, acutely, we controlled that the
      pressure signal transmitted by the telemetry system was accurate and corresponded
      to a signal obtained with a high-fidelity Millar catheter. Second, we evaluated
      the chronic consequences of implantation of the system. Third, we used the system
      to monitor pulmonary arterial pressure in a model of monocrotaline-induced
      hypertension in which the effects of bosentan, an endothelin-receptor antagonist,
      were evaluated. The telemetry system was reliable and did not lead to damage of
      the right ventricle and/or to chronic pulmonary embolism. After a recovery period
      of 8-10 days, mean pulmonary arterial pressure was stable. With the use of this
      telemetry system, it was possible to follow the increase of pulmonary arterial
      pressure induced by monocrotaline. In this model, bosentan decreased mean
      pulmonary arterial pressure by 13% (P = 0.07), suggesting a role of endothelin in
      this model of pulmonary hypertension. We conclude that it is possible to use this
      telemetry system to monitor pulmonary arterial pressure in freely moving
      conscious rats.

PMID- 8872677
TI  - Hypercapnic and hypoxic ventilatory responses.

PMID- 8872678
TI  - Distinct scattering in basal values of oxygen consumption.

PMID- 8872679
TI  - Will the anesthesia question always remain debatable?

PMID- 8872680
TI  - The last days of William Thomas Green Morton.

PMID- 8872681
TI  - Lexicographic history of "anesthesia".

PMID- 8872682
TI  - Postoperative opioid analgesia--reconsider, don't reject.

PMID- 8872683
TI  - Postoperative opioid analgesia: time for a reconsideration?
AB  - Postoperative pain relief has improved in recent years with the development of
      new analgesics, additional routes of administration and the appearance of the
      hypothesis of preemptive as well as balanced analgesia (Kehlet H; Postoperative
      pain relief-what is the issue? Br J Anaesth 1994;72:375-8). Many initial
      improvements simply involved the administration of opioid analgesics in new ways,
      such as continuous or on demand intravenous (i.v.) or epidural infusion. These
      methods allow lower total opioid dosages, provide a more stable concentration of
      opioid at the receptor and correspondingly better analgesic effects, and also
      fewer unwanted side effects. Although opioids have played a prominent role in
      postoperative analgesia for centuries and are still often administered as a
      matter of routine, their frequent minor side effects and the increasing
      availability of suitable alternatives may limit their future use in some
      situations. Thus, the recent emphasis on ambulatory surgery and accelerated
      surgical stay programs, both with a focus on early recovery of organ function and
      provision of functional analgesia [i.e., pain relief that allows normal function
      (Kehlet H: Postoperative pain relief-what is the issue? Br J Anaesth 1994;72:375
      8)] provide an opportunity for a reappraisal of opioid use in these settings. For
      this debate, controlled clinical studies on the opioid-sparing effect of
      different analgesic techniques are mentioned, and preferably studies with
      multiple dosing of analgesics and/or a reasonably large patient sample size.
      These data do not allow a proper meta-analysis to be performed because of the
      large variability in surgical procedures, dosing regimens, assessment criteria,
      among others.

PMID- 8872684
TI  - Effects of regional anesthesia on perioperative outcome.
AB  - To provide an overview of current knowledge, this article reviews experimental
      and clinical data from investigations examining effects of regional anesthesia on
      perioperative morbidity in specific physiologic systems. The issues of morbidity
      and mortality following general and regional anesthesia are addressed, as are the
      development of perioperative thromboembolism and blood loss, which are known to
      be increased during general anesthesia. Finally, the effects of regional
      anesthesia on the vascular system, the perioperative stress response, and the
      pulmonary function are discussed.

PMID- 8872685
TI  - Effects of enflurane and isoflurane on splanchnic oxygenation in humans.
AB  - STUDY OBJECTIVES: To determine the effects of enflurane and isoflurane on hepatic
      venous oxygen saturation (ShvO2) and splanchnic oxygen (O2) extraction. To
      measure hemodynamic parameters and ShvO2, mixed venous, and arterial lactate
      concentrations during enflurane and isoflurane anesthesia. DESIGN: Randomized,
      prospective study. SETTING: University hospital. PATIENTS: 20 ASA physical status
      I, II, and III adults, who underwent major abdominal surgery requiring mechanical
      ventilation a few hours postoperatively. INTERVENTIONS: After placement of
      catheters in the pulmonary artery, radial artery, peripheral and right hepatic
      vein, one hour postoperatively either enflurane or isoflurane was applied at
      different minimum alveolar concentration (MAC) of 0.5, 1.0, and 1.5 in a
      randomized order. MEASUREMENTS AND MAIN RESULTS: Before and 10 minutes after
      administration of each desired end-expiratory anesthetic concentration, the
      following parameters were determined: hemodynamic parameters, arterial (SaO2),
      mixed venous (SvO2), and hepatic venous oxygen saturations, systemic and
      splanchnic O2 extraction, arterial, mixed venous, and hepatic venous lactate
      concentrations. Cardiac output (CO) and mean arterial pressure (MAP) decreased in
      a dose dependent manner. SaO2, SvO2, and systemic O2 extraction remained
      unchanged with enflurane and isoflurane anesthesia. In the enflurane group, but
      not in the isoflurane group, ShvO2 decreased with increasing inhalational
      concentrations. This decrease in ShvO2 reflected an increase in splanchnic O2
      extraction with enflurane; in contrast to isoflurane. CONCLUSIONS: Enflurane
      causes a decrease in ShvO2, which indicates an impairment of splanchnic perfusion
      corresponding to the reduction in CO and MAP in a dose-dependent manner.
      Isoflurane maintains splanchnic perfusion in contrast to enflurane.

PMID- 8872686
TI  - Propofol at conscious sedation doses produces mild analgesia to cold pressor
      induced pain in healthy volunteers.
AB  - STUDY OBJECTIVE: To determine whether subanesthetic doses of propofol have
      analgesic effects in healthy volunteers. DESIGN: Prospective, double-blind,
      placebo-controlled, randomized, crossover trial. SETTING: Human psychomotor
      performance laboratory within our anesthesia and critical care department.
      SUBJECTS: 12, non-drug abusing volunteers, aged 22 to 38 years. INTERVENTIONS:
      Five drug conditions were used in which a loading injection was followed by a 20
      minute infusion period: placebo [saline (Intralipid)] injection, Intralipid
      infusion; propofol 0.125 mg/kg injection, propofol 12.5 mcg/kg/min infusion;
      propofol 0.25 mg/kg injection, propofol 25 mcg/kg/min infusion; propofol 0.5
      mg/kg injection, propofol 50 mcg/kg/min infusion; fentanyl 1.4 mcg/kg injection
      (positive control), Intralipid infusion. Five minutes into the infusion period
      and 115 minutes after the infusion period was terminated, subjects immersed their
      forearms in ice-cold water for three minutes while pain assessments were
      recorded. MEASUREMENTS AND MAIN RESULTS: Propofol at the two higher doses during
      part of the first immersion produced a significant reduction (p < 0.05) in pain
      intensity and bothersomeness ratings. However, relative to fentanyl, the
      analgesia was mild. Propofol did not affect any ratings on the 15-item short-form
      McGill Pain Questionnaire, whereas fentanyl reduced 10 of the ratings.
      CONCLUSION: Our laboratory results are consistent with the commonly accepted
      clinical practice of supplementing propofol with an opioid in conscious sedation
      procedures to provide a satisfactory level of pain relief.

PMID- 8872687
TI  - Medical waste in the environment: do anesthesia personnel have a role to play?
AB  - STUDY OBJECTIVE: To conduct a feasibility study of the mechanics of recycling
      single-use anesthesia breathing systems and practices of anesthesiologists and
      nurse-anesthetists in a tri-state region. STUDY DESIGN: Two-part, open,
      prospective analysis using pre-printed questionnaire and cost/time analysis of
      labor and materials. SETTING: Questionnaire sent to 413 anesthesiology
      departments in Pennsylvania, New Jersey, and Delaware, and hospital/recycling
      facility for evaluation of time and cost. MEASUREMENTS AND MAIN RESULTS: Time to
      disassemble and sort the breathing circuits, analysis of costs and obtainable
      income from byproducts of recycling, and standard survey questionnaire concerning
      demographic characteristics of respondents and individual department/hospital
      practitioners. Data analysis included analysis of variance and Kruskal-Wallis
      tests. Pilot analysis: Sorting of circuits to economic component required ten
      minutes at an average cost of $1.60 Value of scraps obtainable was $3.44, leaving
      a gross margin of $1.84 for a box of 18 circuits. Benefit analysis: Extended
      reduction in the regulated medical waste in our operating room of 16,875 lb,
      saving $4,387.50 per year. With generation of revenue from scrap, the net gain is
      $5,994.64 per yr. Questionnaire: Majority (83%) of departments polled would
      participate in recycling implemented by suppliers. Most respondents would not
      consider (58%) recycling unless mandated by law. CONCLUSION: The program
      described is cost-effective and environmentally beneficial.

PMID- 8872688
TI  - Parental presence plus oral midazolam decreases frequency of 5% halothane
      inductions in children.
AB  - STUDY OBJECTIVE: To determine the frequency of 5% halothane induction and
      behavioral distress during inhalation induction with both oral midazolam and
      parental presence compared with parental presence alone. DESIGN: Randomized,
      controlled, double blind study. SETTING: Same day anesthesia at a university
      department of anesthesiology. PATIENTS: 72 ASA status I and II children, 3 to 10
      years of age, scheduled for first time anesthesia. INTERVENTIONS: Children were
      assigned to one of two groups to receive midazolam 0.5 mg/kg orally or placebo. A
      parent was present during induction. Children were videotaped at baseline, after
      treatment, and during induction. Tapes were scored for behavioral distress using
      the revised Observational Scale of Behavioral Distress. MEASUREMENTS AND MAIN
      RESULTS: Children who received midazolam in the setting of parental presence had
      significantly fewer 5% halothane inductions than those who received placebo (p <
      0.02). They also had less behavioral distress (p < 0.01). CONCLUSIONS: The
      combination of parental presence plus oral midazolam reduces the likelihood of
      needing a 5% rapid halothane induction when compared with parental presence
      without premedication.

PMID- 8872689
TI  - A mixture of mivacurium and rocuronium is comparable in clinical onset to
      succinylcholine.
AB  - STUDY OBJECTIVES: To compare the clinical onset and duration of a combination of
      mivacurium and rocuronium with succinylcholine, and to determine the efficacy of
      this mixture for rapid tracheal intubation. DESIGN: Observer-blind prospective
      study. SETTING: Teaching hospital. PATIENTS: 70 ASA status I and II patients
      having general anesthesia for elective surgery. MEASUREMENTS AND MAIN RESULTS:
      After induction of general anesthesia, patients randomly received succinylcholine
      1.0 mg/kg, rocuronium 0.6 mg/kg, or a combination of rocuronium 0.6 mg/kg and
      mivacurium 0.15 mg/kg. Evoked muscular response at the adductor pollicis was
      measured by mechanomyography. The time from injection of muscle relaxant(s) to
      ablation of T1 (clinical onset) and recovery of T1 to 25% of control height
      (clinical duration) was recorded. Intubating conditions 45 seconds after
      administration of muscle relaxants were assessed. There was no significant
      difference in clinical onset time between succinylcholine (mean +/- SD, 47.4 +/-
      6.5 seconds) and the combination of mivacurium-rocuronium (51.2 +/- 13.4
      seconds). Intubating conditions with mivacurium-rocuronium were comparable to
      those of succinylcholine. The clinical duration of rocuronium 0.6 mg/kg (38.9 +/-
      12.3 minutes) was prolonged by the addition of mivacurium (49.0 +/- 9.6 minutes).
      CONCLUSIONS: This combination of mivacurium and rocuronium is comparable to
      succinylcholine in both clinical onset time and quality of intubating conditions.
      When rapid onset of dense neuromuscular blockade and intermediate clinical
      duration is desirable, this mixture may be an acceptable alternative to
      succinylcholine.

PMID- 8872690
TI  - Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to
      laryngoscopy and intubation: a double-blind, controlled clinical trial.
AB  - STUDY OBJECTIVES: To evaluate the efficacy of intravenous lidocaine and two doses
      of esmolol for attenuating the cardiovascular responses to laryngoscopy and
      intubation, and to assess whether a combination of both drugs is more effective
      than either drug alone. DESIGN: Randomized, prospective, double-blind, placebo
      controlled study. SETTING: University hospital. PATIENTS: 90 ASA status I and II
      normotensive women scheduled for elective gynecologic procedures with general
      anesthesia. INTERVENTIONS: Induction of anesthesia was standardized for all
      patients. The first group received lidocaine 1.5 mg/kg (Group LID); the second
      and third groups received esmolol 1 mg/kg and 2 mg/kg, respectively (Groups E1
      and E2, respectively); the fourth group received lidocaine 1.5 mg/kg and esmolol
      1 mg/kg (Group LID-E1); the fifth group received lidocaine 1.5 mg/kg and esmolol
      2 mg/kg (Group LID-E2); the sixth group received saline as a placebo (Group
      PLAC). MEASUREMENTS AND MAIN RESULTS: Systolic blood pressure and heart rate (HR)
      were recorded before induction, before injection of the first test drug,
      immediately before laryngoscopy, and 1, 2, and 5 minutes following intubation.
      Duration of laryngoscopy was recorded. Only patients receiving placebo had
      increased HR values after intubation compared with baseline values (p < 0.05).
      The proportion of patients with a maximum HR exceeding 90 beats/min was
      significantly higher in the placebo group (8 of 15 patients) than in both esmolol
      groups (E1 2 of 15; E2 2 of 15) (p < 0.05). Systolic blood pressure values after
      tracheal intubation did not differ among groups except for those receiving the
      combinations of lidocaine and esmolol, and they had significantly lower blood
      pressure (BP) values compared with placebo (p < 0.05). CONCLUSIONS: Esmolol 1 to
      2 mg/kg is reliably effective in attenuating HR response to tracheal intubation.
      Neither of the two doses of esmolol tested nor that of lidocaine affected the BP
      response. Only the combination of lidocaine and esmolol attenuated both HR and BP
      responses to tracheal intubation.

PMID- 8872691
TI  - Hemodynamic effects of intrathecal sufentanil compared with epidural bupivacaine
      in laboring parturients.
AB  - STUDY OBJECTIVES: To provide information on the central hemodynamic effects of
      intrathecal sufentanil after a standard intravenous preload using thoracic
      bioimpedance monitoring to obtain noninvasive measurements of cardiac index (CI),
      stroke index (SI), and systemic vascular resistance (SVR). To compare hemodynamic
      parameters after intrathecal sufentanil labor analgesia to those after a standard
      dose of epidural bupivacaine in laboring parturients. DESIGN: Randomized, double
      blind study. SETTING: Labor and delivery unit in a university hospital. STUDY
      DESIGN: 40 ASA status I parturients were randomized into two groups receiving
      analgesia with combined spinal-epidural technique. Group SUF received 10
      micrograms of intrathecal sufentanil followed by 12 ml of saline through an
      epidural catheter; Group BUP received 2 ml of intrathecal saline followed by 12
      ml of 0.25% epidural bupivacaine. Heart rate (HR), blood pressure (BP), and
      thoracic bioimpedance monitoring were recorded. Pain scores, fetal HR, and side
      effects were noted. MEASUREMENTS AND MAIN RESULTS: No significant changes from
      baseline were seen in CI, SI, or SVR index. Mean arterial pressure was lower in
      Group BUP at 10 and 20 minutes after induction of analgesia. Mean HR was lower in
      Group SUF at 20 and 30 minutes after induction. Two patients in Group SUF and
      four patients in Group BUP experienced hypotension requiring ephedrine. Pain
      scores were lower in Group SUF at 10 minutes after induction of analgesia;
      subsequent pain scores and duration of analgesia were similar. Fourteen patients
      in Group SUF experienced itching. CONCLUSIONS: No significant differences in CI,
      SI, or SVR index were seen after either method of analgesia. A few patients in
      both groups experienced hypotension requiring treatment with ephedrine. Both
      techniques of labor analgesia appear to provide effective pain relief but care
      must be taken with either method to monitor maternal BP.

PMID- 8872692
TI  - Intraoperative hypothermia associated with lower extremity tourniquet deflation.
AB  - STUDY OBJECTIVE: To determine the rapidity and extent of core temperature
      decrease following release of a lower extremity pneumatic tourniquet. DESIGN:
      Prospective study. SETTING: Inpatient surgery in a university trauma center.
      PATIENTS: 11 ASA status I and II adults undergoing unilateral lower extremity
      fracture fixation in which a tourniquet was used, with general anesthesia.
      INTERVENTIONS: Temperature was measured in the esophagus before and after lower
      extremity tourniquet release. MEASUREMENTS AND MAIN RESULTS: Tourniquet times
      ranged from 41 to 129 minutes (mean 98.5 +/- 9.1 minutes). Following tourniquet
      deflation core temperature decreased in all patients, with a maximal decline at
      10 minutes, the termination of measurements, although trending downward.
      Esophageal temperature decreased an average of 0.46 degree C +/- 0.2 degree C at
      5 minutes, and 0.67 degree C +/- 0.2 degree C at 10 minutes following tourniquet
      release, respectively. Temperature changes were significant (p = 0.0001) at both
      time intervals. CONCLUSION: Core temperature drops significantly immediately
      following release of the tourniquet at the esophageal temperature monitoring
      site. This decrease is the result of cooling of systemic blood reperfusing the
      hypothermic limb, and mixing of cool, "washed out" blood with the systemic
      circulation. As the consequences of hypothermia are well-known, we recommend core
      temperature monitoring in all patients having lower extremity tourniquet placed
      during general anesthesia, as well as vigilant monitoring for prolonged effects
      of anesthetics in the postoperative period.

PMID- 8872693
TI  - Preoperative preparation in children: a cross-sectional study.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of a behavioral preparation
      program on reducing anxiety in children and their parents prior to elective
      surgery. DESIGN: Cross-sectional study. SETTING: A children's hospital. PATIENTS:
      143 children undergoing outpatient surgery, and their parents. INTERVENTIONS: A
      behavioral preoperative preparation program. MEASUREMENTS AND RESULTS: Overall
      anxiety in children and their parents did not differ significantly between the
      group that received the preoperative program and the group that did not (p = NS).
      Children older than 6 years were least anxious on separation from their parents
      if they participated in the preparation program more than 5 to 7 days prior to
      surgery, moderately anxious if they did not receive preparation, and most anxious
      if they received the preparation 1 day prior to surgery (P = 0.04). Multivariable
      regression analysis (for overall model, F = 2.14, p = 0.02) revealed that
      although the preparation program itself was not a predictor of a child's behavior
      on separation to the operating room, the interaction between child's age and
      timing of the program (p = 0.003), and child's previous hospitalization were
      predictors of children's anxiety response. Similarly, in the preoperative holding
      area, independent predictors of anxiety included timing of the preparation
      program, age of child, and the child's baseline temperament characteristics.
      CONCLUSIONS: The results highlight the complexities in assuming that a behavior
      based preoperative preparation program is effective for all pediatric
      outpatients. The effects of such an intervention vary with the child's age, the
      timing of the intervention, and a history of previous hospitalization.

PMID- 8872694
TI  - Preoperative glycopyrrolate: oral, intramuscular, or intravenous administration.
AB  - STUDY OBJECTIVE: To evaluate the effects of oral, intramuscular (i.m.) and
      intravenous (i.v. glycopyrrolate on oral and gastric secretions, and to assess
      how these routes of administration change intubating conditions. DESIGN:
      Randomized, double-blinded study. SETTING: University hospital operating room.
      PATIENTS: 37 ASA status I and II general anesthesia patients. INTERVENTIONS:
      Patients were randomized to receive glycopyrrolate or placebo just before surgery
      by three routes: oral, i.m., and i.v.. Glycopyrrolate was received once by one
      route and placebo by the other two routes. A placebo group received three
      placebos and no glycopyrrolate. MEASUREMENTS AND MAIN RESULTS: Mouth conditions
      and intubating conditions were qualitatively assessed by the patient and the
      intubating anesthesiologist. No difference between groups was noted. Oral and
      gastric volumes were measured and showed significantly less gastric volume for
      the i.v. group as compared with the other groups. Oral secretions were reduced in
      both the i.v. and i.m. groups when compared with placebo or glycopyrrolate
      administered orally. CONCLUSIONS: Preoperative glycopyrrolate is significantly
      more effective at reducing oral and gastric secretions if administered
      intravenously immediately before induction.

PMID- 8872695
TI  - Intraoperative air embolism with pulse irrigation device.
AB  - Venous air embolism is a potentially fatal complication. In a patient undergoing
      extensive debridement of an open perineal wound, hemodynamically significant air
      embolization occurred during use of a pulsatile saline irrigation device. We
      describe another intraoperative setting in which venous air embolism is a risk.

PMID- 8872696
TI  - A case of coronary artery spasm during spinal anesthesia.
AB  - We present a rare case of coronary artery spasm during spinal anesthesia in a
      patient who had neither complications nor prior history of coronary artery
      disease. Some factors are involved in the occurrence of perioperative coronary
      artery spasm. Many cases of coronary artery spasm during general anesthesia, or
      general plus epidural anesthesia, have been reported. Although spinal anesthesia
      by itself has not been reported to be a cause of coronary artery spasm, it is
      likely, in the current case, that the combination of the activated
      parasympathetic nerve system by the retraction of the peritoneum and spinal
      anesthesia might have caused the coronary artery spasm. Anesthesiologists need to
      be aware that coronary artery spasm may occur during spinal anesthesia,
      especially when the peritoneum is retracted.

PMID- 8872697
TI  - What needs to be said? Informed consent in the context of spinal anesthesia.

PMID- 8872698
TI  - The copper kettle: a historical perspective.
AB  - Until 1952, the administration of inhaled volatile anesthetics was inexact
      because vaporizers in general use were not calibrated for either concentration or
      volume of vapor produced. These devices diverted a variable portion of fresh gas
      flow either through or over the liquid to be vaporized, but they lacked vernier
      or fine control. Therefore, changes in the concentration of the anesthetic vapor
      were not easily controlled. Dr. Lucien E. Morris standardized the administration
      of volatile anesthetics with his invention of the Copper Kettle, which produced
      known volumes of saturated vapor, then diluted to calculated concentrations
      necessary for anesthesia. To achieve this, modifications had to be made in the
      liquid container, circuit design, and vaporizing surfaces in use at the time.
      Morris' design incorporated a separately metered flow of carrier gas through the
      vaporizer to produce known volumes of saturated vapor for introduction into the
      fresh gas flow delivery.

PMID- 8872699
TI  - Spinal ignorance.

PMID- 8872700
TI  - Distributed processing on the basis of parallel and antagonistic pathways
      simulation of the femur-tibia control system in the stick insect.
AB  - In inactive stick insects, sensory information from the femoral chordotonal organ
      (fCO) about position and movement of the femur-tibia joint is transferred via
      local nonspiking interneurons onto extensor and flexor tibiae motoneurons.
      Information is processed by the interaction of antagonistic parallel pathways at
      two levels: (1) at the input side of the nonspiking interneurons and (2) at the
      input side of the motoneurons. We tested by a combination of physiological
      experiments and computer simulation whether the known network topology and the
      properties of its elements are sufficient to explain the generation of the motor
      output in response to passive joint movements, that is resistance reflexes. In
      reinvestigating the quantitative characteristics of interneuronal pathways we
      identified 10 distinct types of nonspiking interneurons. Synaptic inputs from fCO
      afferents onto these interneurons are direct excitatory and indirect inhibitory.
      These connections were investigated with respect to position and velocity signals
      from the fCO. The results were introduced in the network simulation. The motor
      output of the simulation has the same characteristics as the real system, even
      when particular types of interneurons were removed in the simulation and the real
      system.

PMID- 8872701
TI  - Dissection and reduction of a modeled bursting neuron.
AB  - An 11-variable Hodgkin-Huxley type model of a bursting neuron was investigated
      using numerical bifurcation analysis and computer simulations. The results were
      applied to develop a reduced model of the underlying subthreshold oscillations
      (slow-wave) in membrane potential. Two different low-order models were developed:
      one 3-variable model, which mimicked the slow-wave of the full model in the
      absence of action potentials and a second 4-variable model, which included
      expressions accounting for the perturbational effects of action potentials on the
      slow-wave. The 4-variable model predicted more accurately the activity mode
      (bursting, beating, or silence) in response to application of extrinsic stimulus
      current or modulatory agents. The 4-variable model also possessed a phase
      response curve that was very similar to that of the original 11-variable model.
      The results suggest that low-order models of bursting cells that do not consider
      the effects of action potentials may erroneously predict modes of activity and
      transient responses of the full model on which the reductions are based. These
      results also show that it is possible to develop low-order models that retain
      many of the characteristics of the activity of the higher-order system.

PMID- 8872702
TI  - Investigation of the role of interneurons and their modulation by centrifugal
      fibers in a neural model of the olfactory bulb.
AB  - Olfactory bulb processing results from the interaction of relay neurons with two
      main categories of interneurons which mediate inhibition in two distinct layers:
      periglomerular cells and granule cells. We present here a neural model of the
      mammalian olfactory bulb which allows to separately investigate the functional
      consequences of the two types of interneurons onto the relay neurons
      responsiveness to odors. The model, although built with simplified
      representations of neural elements generates various aspects of neural dynamics
      from the cellular to the populational level. We propose that the combined action
      of centrifugal control at two different layers of processing is complementary:
      reduction of the number of active relay neurons responding to a given odorant
      through increased activity of periglomerular cells, and an increase of response
      intensity of active mitral cells through decrease of granule cell inhibition.

PMID- 8872703
TI  - A quantitative population model of whisker barrels: re-examining the Wilson-Cowan
      equations.
AB  - Beginning from a biologically based integrate and fire model of a rat whisker
      barrel, we employ semirigorous techniques to reduce the system to a simple set of
      equations, similar to the Wilson-Cowan equations, while retaining the ability for
      both qualitative and quantitative comparisons with the biological system. This is
      made possible through the clarification of three distinct measures of population
      activity: voltage, firing rate, and a new term called synaptic drive. The model
      is activated by prerecorded neural activity obtained from thalamic "barreloid"
      neurons in response to whisker stimuli. Output is produced in the form of
      population PSTHs, one each corresponding to activity of spiny (excitatory) and
      smooth (inhibitory) barrel neurons, which is quantitatively comparable to PSTHs
      from electrophysiologically studied regular-spike and fast-spike neurons. Through
      further analysis, the model yields novel physiological predictions not readily
      apparent from the full model or from experimental studies.

PMID- 8872704
TI  - A genetic study of dentin growth in the mandibular second and third molars of
      male mice.
AB  - Although the influence of genetic and environmental factors on the completed
      crown size of mandibular molars in mice is well known, such influence on the
      growth process of the mandibular second and third molars of mice has not yet been
      clarified. The purpose of the present study is to examine the growth pattern of
      the dentinal formation and evaluate the relative contributions of both genetic
      and environmental factors to longitudinal dentin formation by the use of the
      partial diallel cross-genetic approach, the time-marking method and a
      computerized image measurement system. The following results were obtained: 1)
      the onset of dentinal formation in the second molar was on the 6-9th day after
      birth, while that of the third molar was on the 9-12th day after birth; 2) the
      best fitted growth curve of the dentinal formation for the first molar was the
      fifth order polynomial equation, while for the second molar the fourth order
      polynomial equation was best, and for the third molar the third order polynomial
      equation was best; 3) maternal effect strongly influenced the second and the
      third molar dentin growth at an early stage of postnatal growth. Thus, it could
      be concluded that the dentinal formation growth pattern differed among the three
      kinds of mouse molars while maternal environmental factors, in addition to
      genetic factors, played an important role in the mouse second and third molar
      dentin growth during the early stage of postnatal growth.

PMID- 8872705
TI  - Abnormalities in secondary cartilages in four lines of transgenic mice harboring
      two different types of mutations in the cartilage-specific type II collagen gene.
AB  - A histological analysis was performed on two secondary cartilages, the mandibular
      condyle and the medial end of clavicle, in transgenic mice harboring two
      different types of mutations in the cartilage-specific type II collagen gene.
      Considerable differences were observed in the maturation zone of the chondrocytes
      and the hypertrophic cells of the growth regions of the two secondary cartilages
      examined between the transgenic mice and their transgene-negative littermates,
      which served as controls. Looseness of the perichondrium/periosteum was a
      distinct feature seen in both mutations. However, phenotypic consequences of the
      mutations in secondary cartilages were less severe than those in primary
      cartilages. We propose that the differences between primary and secondary
      cartilages are due to differences in their origin, mode of growth, architecture
      and behavior under extrinsic factors.

PMID- 8872706
TI  - Mild dental findings associated with severe osteogenesis imperfecta due to a
      point mutation in the alpha 2(I) collagen gene demonstrate different expression
      of the genetic defect in bone and teeth.
AB  - Serial intraoral photographs, radiographs, and ground sections from an extracted
      upper permanent canine served to characterize dental abnormalities in a 15-year
      old girl suffering from severe (type III) osteogenesis imperfecta (OI) due to a
      point mutation that substituted glycine 688 of the alpha 2(I) chain of collagen I
      by serine. Dental records showed that all deciduous teeth exhibited clinical and
      radiographic characteristics of dentinogenesis imperfecta (DI), whereas permanent
      teeth including the removed canine appeared normal, although pulp chambers
      contained unusually large denticles. Despite the unconspicuous clinical
      appearance of the canine, histologic sections revealed small, canal-like,
      hypomineralized hard tissue patches that lacked a regular tubular structure and
      occupied a narrow band of the bulk of normal circumpulpal dentin at about the
      level of the cemento-enamel junction. The finding that a mutation in the gene for
      the alpha 2(I) collagen chain with serious consequences in bone has only minor
      effects in teeth would suggest that odontoblasts, unlike osteoblasts, can largely
      compensate for this particular genetic defect, possibly by excluding the abnormal
      alpha 2(I) chains and forming alpha 1(I) homotrimeric collagen I. The discrepant
      consequences in deciduous as opposed to permanent teeth and the specific
      localization of the dentinal abnormalities in permanent teeth lead us to
      speculate that the exclusion of defective alpha 2(I) chains could depend on the
      developmental stage and/or the rate of extracellular matrix formation.

PMID- 8872707
TI  - Phenotypic features of dentition in diastrophic dysplasia.
AB  - Diastrophic dysplasia (DTD) is a well-characterized, recessively inherited
      osteochondrodysplasia. The gene, DTDST, in which mutations are responsible for
      the disease, codes for a sulphate transporter protein. We studied 53 patients
      with earlier diagnosed DTD for special characteristics in the oral region.
      Clinical examination included impressions of dental arches, oral photographs, and
      panoramic radiographs. Palatal clefting was recorded. Congenitally missing teeth
      were evaluated and dental maturity calculated from the panoramic radiographs.
      Tooth crown size and length and breadth of dental arches were measured from the
      casts. Dental anomalies and orthodontical status were evaluated from the casts
      and oral photographs. The level of oral hygiene was evaluated with caries (DMF)
      and periodontal (GBI) indices. Cleft palate was recorded in 56% and hypodontia
      (excluding third molars) in 31% of the patients. Dental age was retarded. Dental
      arches were narrow and tooth crown size was reduced. The observed crown size
      reduction could result from the same factors that cause cleft palate and/or
      hypodontia, or from a lack of sulfation in the developing dental papilla. The
      typical malocclusion traits were crowding, lateral crossbite, and open bite,
      which we assumed to result from reduced growth potential of the dental arches.
      Despite crowding and limited flexion of the finger joints leading to a severe
      handicap, the level of oral hygiene was high and no need for auxiliary equipment
      for cleaning the teeth was noted.

PMID- 8872708
TI  - Microanatomy of the dental enamel in autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy (APECED): report of three cases.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an
      autosomal recessive disease composed of failure of various endocrine glands,
      chronic mucocutaneous candidiasis, and an ectodermal dystrophy complex including
      hypoplasia of the dental enamel. To characterize the enamel defect further, we
      studied enamel microanatomy by light microscopy and scanning electron microscopy
      in clinically affected permanent teeth from three APECED patients. In all three
      cases, the enamel was partially hypoplastic and morphologically aberrant.
      Hypoplasia was evident as a horizontal band or as rows of pits. The incremental
      pattern in the abnormal enamel was obscure, and the prisms were either barely
      detectable or accentuated and disoriented. In scanning electron microscopy,
      imprints of the Tomes processes were seen on the enamel surface, but the
      perikymata were poorly contoured. The distribution pattern of the defective
      enamel corresponded to the sequence of tooth development and was suggestive of a
      transient insult. In the enamel affected with a hypoplastic pitted from of
      amelogenesis imperfecta, studied for comparison, only local hypoplastic defects
      were seen. Together with normal parathyroid function in one patient and normal
      calcification of dentin in one of the two patients with hypoparathyroidism,
      morphology of the enamel in APECED appears to preclude calcium deficiency as the
      primary cause of the enamel dystrophy.

PMID- 8872709
TI  - Postpubertal growth and development of the face in unilateral cleft lip and
      palate as compared to the pubertal period: a longitudinal study.
AB  - X-ray cephalometry was used for the assessment of 22 boys and 23 girls with
      complete unilateral cleft lip and palate who were treated with the same surgical
      method. They were examined at the age of 10 years and in adulthood. In the group
      of 13 boys and 15 girls, examined also at the age of 15 years, were analysed
      intersexual differences of facial growth and development during the postpubertal
      period and the results were compared with those obtained during the pubertal
      period. The data showed that in boys facial growth persists after the age of 15
      years and in the region of the upper face attains about half the values recorded
      in the period of puberty, while mandibular growth attains almost the same values
      as during puberty. In girls the growth is almost terminated but for the lower
      jaw, where it is still significant though several times slighter than during
      puberty. In both sexes there is only a minimum growth of maxillary depth and of
      upper lip height during the postpubertal period, as well as during the pubertal
      period. The highest growth rate shows the depth of the nose. Because of the
      intersexual differences in the amount of postpubertal growth, developmental
      changes in facial configuration do not occur in girls during this period, while
      in boys a further deterioration of maxillary protrusion, of sagittal jaw
      relations, and of the upper lip prominence continues, as well as an increase of
      the flattening of the face. In contrast to the pubertal period in both sexes, a
      proclination of upper incisors and an improvement of overjet was not attained.
      Contrary to the pubertal period, in the postpubertal period, intersexual
      differences in the amount of growth and of the developmental changes in the shape
      and position of facial characteristics were recorded. Therefore during studies of
      the growth and development of the face, it is not possible to pool both sexes
      without some reservations. This holds true in particular in the postpubertal
      period.

PMID- 8872710
TI  - Characteristics of milk and reduced fat cheddar cheese from cows fed extruded
      soybeans and niacin.
AB  - A control diet and three experimental diets were fed to midlactation Holstein
      cows to evaluate the effects of dietary unsaturated fatty acids and niacin on
      milk and reduced fat Cheddar cheese. The diet consisted mainly of rolled corn and
      soybean meal in the concentrate mixture. Experimental diets consisted of the
      control diet with added niacin and the control diet but with extruded soybeans
      substituted for part of the corn and soybean meal, with and without added niacin.
      Milks from cows fed diets of extruded soybean and extruded soybeans with added
      niacin contained lower concentrations of short- and medium-chain fatty acids and
      higher concentrations of long-chain fatty acids. Cheese milks consisted of a
      control, a homogenized control (3.45 MPa), and unhomogenized and homogenized
      milks (3.45 MPa) from cows fed extruded soybeans with added niacin. Reduced fat
      Cheddar cheeses produced from unhomogenized and homogenized milks from the cows
      fed extruded soybeans with added niacin contained higher concentrations of
      unsaturated fatty acids. The reduced fat Cheddar cheeses maintained acceptable
      flavor, body, and texture during storage. Homogenization of cheese milk had
      little effect on cheese properties. Cheeses manufactured from milks with high
      amounts of unsaturated fatty acids were softer; however, this difference was not
      detected by the sensory panel.

PMID- 8872711
TI  - Growth characteristics of bifidobacteria in infant formulas.
AB  - Four species of bifidobacteria, Bifidobacterium bifidum (ATCC 15696),
      Bifidobacterium breve (ATCC 15700), Bifidobacterium infantis (ATCC 15697), and
      Bifidobacterium longum (ATCC 15708), were grown anaerobically at 37 degrees C in
      lactobacilli MRS broth with 0.5% cysteine-HC1 and inoculated at 2.5% into three
      types of infant formula (based on soy, or milk, or casein hydrolysate) and in
      nonfat milk followed by incubation at 37 degrees C for 24 h. In most cases, the
      logarithmic phase of growth for all species varied from the first 8 to 12 h
      postinoculation. Generation times for B. longum and B. breve were similar, and
      times for B. infantis were shortest, in all of the formulas. Trends for lactic
      acid production for all species in all the formulas were similar to trends for
      acetic acid production. Counts for formulas based on soy or milk were similar for
      all species except B. bifidum, and those for casein-hydrolyzed formula were
      always lowest for all species except B. bifidum, for which count was maximal with
      the formula based on soy. Results suggest that growth characteristics of
      bifidobacteria in infant formula were species specific and formula dependent and
      that growth was maximal in the formula based on milk.

PMID- 8872712
TI  - Effect of bifidogenic factors on growth characteristics of bifidobacteria in
      infant formulas.
AB  - A bifidogenic factor, lactulose or fructooligosaccharides, was added (0.5%) into
      infant formula based on soy or infant formula with hydrolyzed casein. The infant
      formulas were then inoculated (2.5%) with Bifidobacterium bifidum (ATCC 15696),
      Bifidobacterium breve (ATCC 15700), Bifidobacterium infantis (ATCC 15697), or
      Bifidobacterium longum (ATCC 15708) or their mixture (mixed culture) and
      incubated at 37 degrees C for 24 h. Lactulose did not influence maximal counts or
      generation times in either formula for any species except B. infantis, which had
      lower counts. Trends of developed acidity and pH of the mixed culture in the
      infant formulas with or without lactulose were similar to those for B. breve.
      Maximal counts and generation times remained unchanged with or without
      fructooligosaccharides for all species and the mixed culture, except for B.
      bifidum in the formula based on soy, for which maximal counts did not occur.
      Growth in either formula was inhibited for B. infantis with lactulose and B.
      breve with fructooligosaccharides past 8 h of inoculation.

PMID- 8872713
TI  - Regulation of blood flow in the mammary microvasculature.
AB  - Although milk yield of cows and goats is known to be closely related to the total
      flow of blood through the udder, a number of studies suggest that milk yield can
      vary independently. No studies have attempted to measure the proportion of total
      flow that is nutritive. Within the mammary gland, capillary networks form a
      basket-like architecture surrounding each alveolus. Notably, flow in individual
      capillaries is not constant and varies among capillaries. Capillary flow
      (measured by intravital microscopy) was decreased by oxytocin, which generally
      increased total flow in the mammary artery, suggesting that the proportion of
      total flow that is nutritive can vary. In addition to classic metabolic
      regulators (e.g., carbon dioxide and oxygen) of tissue blood flow, the mammary
      gland produces a number of vasodilatory compounds, including parathyroid hormone
      related protein, insulin-like growth factor-I, prostacyclin, nitric oxide, and
      endothelin. All of these compounds have been shown to alter mammary blood flow.
      Mammary tissue also contains kallikrein and angiotensin-converting enzyme, which
      convert circulating kinins and angiotensin, respectively, into potent vasoactive
      compounds. A number of these compounds are produced by epithelial cells
      themselves, providing a mechanism for the functioning epithelium to control its
      own blood supply and, hence, nutrient flow for milk synthesis. In this review, we
      examine the nature of the mammary microcirculation, its behavior under different
      conditions, and some of the regulatory features of the mammary microvasculature.

PMID- 8872714
TI  - Elevation of lactoferrin gene expression in developing, ductal, resting, and
      regressing parenchymal epithelium of the ruminant mammary gland.
AB  - Accumulation of lactoferrin mRNA in mammary tissue from virgin, pregnant,
      lactating, and involuting ewes and cows was localized using 35S-labeled cRNA
      probes. Expression of lactoferrin was low in the glands of virgin animals. In the
      glands of animals in early pregnancy, very high expression occurred in the ducts
      and immature alveoli, but expression tended to decrease as the alveoli matured.
      In the lactating and involuting gland, expression was generally low or absent in
      actively secreting alveoli and high in alveoli that had an accumulation of
      vesicles in the lumen and secretory epithelium, which was indicative of stasis.
      Occasionally, expression of lactoferrin was seen in cells that appeared to be
      secretory, particularly in involuting glands. Lactoferrin mRNA was expressed not
      only at different sites from other milk protein genes, such as alpha-lactalbumin
      and alpha s1-casein, but also during different stages of mammary development,
      supporting the view that the expression of lactoferrin is regulated differently
      from that of other milk proteins. For all ewes and cows, lactoferrin mRNA was
      detected in the epithelial ducts of the mammary parenchyma and the teat in a
      gradient that increased in ducts nearer the teats. The expression of lactoferrin
      in the ductal epithelium close to the teat was consistent with the antibacterial
      role of lactoferrin.

PMID- 8872715
TI  - Lipid metabolism and intake behavior of dairy cows: effects of intravenous lipid
      and beta-adrenergic supplementation.
AB  - The goal of this experiment was to determine whether modulation of beta 2
      adrenoceptors influenced DMI of lactating dairy cows. Because stimulation of
      these receptors induces mobilization of body fat stores, the effect of such
      stimulation on feed intake was compared with the effect of an intravenous
      administration of lipid nutrients. Four treatments were infused intravenously
      over a 4-h period: 1) a beta 2-agonist (clenbuterol), 2) a beta-blocker
      (propranolol), 3) triglyceride emulsion (lipids), or 4) saline. Two trials were
      carried out for the same four cows to compare the effects of two expected
      lipolytic situations. Trial 1 used cows at 60 DIM treated with infusions from
      0300 to 0700 h, and trial 2 used cows at 92 DIM treated with infusions from 0800
      to 1200 h. Each trial was composed of three consecutive replications of a 4 x 4
      balanced Latin square design with 2-d periods. A complete diet (70% maize silage
      and 30% concentrate) was offered for ad libitum intake. In both trials,
      clenbuterol reduced DMI on the day of infusion (-7.9 and -11.2% for trials 1 and
      2, respectively) and on the following day (-5.1 and -6.3% in trials 1 and 2,
      respectively). This decrease occurred some time after the end of infusion.
      Intravenous lipid supplementation reduced DMI during infusion in both trials and
      during the entire day in trial 2. Both clenbuterol and lipids increased plasma
      NEFA only during infusion. Propranolol had no effect on DMI or basal lipolysis.
      The data demonstrated that stimulating beta 2-adrenoceptors reduced DMI but in a
      manner different from that of lipid energy supplementation.

PMID- 8872716
TI  - Dairy herd management types assessed from indicators of health, reproduction,
      replacement, and milk production.
AB  - Variables related to health, reproduction, replacement, and milk production in
      111 Danish dairy herds were studied with factor analysis. The objectives were to
      identify management types and to assess the relevance of those types for herd
      milk production. Median herd size and total milk production were 59 cows and 7100
      kg of energy-corrected milk, respectively. Based on cow data, 22 herd variables
      were defined. A factor analysis identified 10 first-order factors and 5 second
      order factors. The latter factors were valid indicators of replacement intensity,
      variability of milk production, potential for peak milk production, disease, and
      a complex pattern related to herd size and age, cow size, and live cattle sales.
      The potential for peak milk production, replacement intensity, and variability of
      milk production were strong predictors of herd milk production. Interactions with
      herd size were important. The derived factor scoring coefficients allowed
      assessment of the management type of a given herd.

PMID- 8872717
TI  - The effect of amino nitrogen on the energetics of ruminal bacteria and its impact
      on energy spilling.
AB  - The predominant ruminal bacteria that were obtained from a 10(8) dilution of
      ruminal fluid could be maintained as a mixed population for long periods as long
      as the bacteria were provided with a complex mixture of carbohydrates. Growth of
      predominant ruminal bacteria in carbohydrate-limited, ammonia-excess, continuous
      cultures (0.07/h) had a low requirement for maintenance energy, but the nongrowth
      energy dissipation of ammonia-limited, carbohydrate-excess, predominant ruminal
      bacteria was approximately 10-fold higher (0.96 vs. 0.09 mg of hexose
      equivalent/mg of protein per h, respectively). Mathematical derivations indicated
      that this additional nongrowth energy dissipation could be accommodated by an
      energy spilling function that was independent of the growth rate. Peptides and
      amino acids had little impact on the yield of carbohydrate-limited, ammonia
      excess, continuous cultures (0.07/ h), but amino N greatly increased the growth
      rate and yield of excess-energy batch cultures. The change in growth rate and
      yield that was dependent on amino N indicated that the energy-excess batch
      cultures had the same capacity to spill energy as did the ammonia-limited,
      carbohydrate-excess, predominant ruminal bacteria (0.80 vs. 0.86 mg of hexose
      equivalent/mg of protein per h, respectively). When the energy-excess batch
      cultures were provided with amino N, the growth rate increased, the difference in
      anabolic and catabolic rates was smaller, and less energy was spilled.

PMID- 8872718
TI  - Lactational responses of dairy cows fed unsaturated fat from extruded soybeans or
      sunflower seeds.
AB  - Nine multiparous Holstein cows were used in a replicated 3 x 3 Latin square to
      evaluate the response to diets containing equal amounts of supplemental fat from
      extruded soybeans or sunflower seeds. Both fat sources contained about 66%
      polyunsaturated fatty acids; for soybeans, about 8% was linolenic acid, but
      sunflower seeds contained mostly linoleic acid. Periods were 5 wk, and data were
      collected the last 3 wk of each period. Total mixed diets were (DM basis) 25%
      corn silage, 25% alfalfa hay, and 50% concentrate mix. Control concentrate mix
      contained primarily corn, barley, and soybean meal; extruded soybeans or rolled
      sunflower seeds replaced portions of the corn, barley, and soybean meal in
      isonitrogenous (17% CP) diets. Milk yield was higher for cows fed supplemental
      fat. Percentages of milk fat and protein and DMI were similar for all three
      dietary treatments. Milk fat from cows fed soybeans or sunflower seeds contained
      higher concentrations of unsaturated fatty acids and long-chain fatty acids than
      did milk fat from cows fed the control diet. Milk yield and composition were
      similar for cows fed soybeans, or sunflower seeds. Soybeans or sunflower seeds
      can be used as dietary fat supplements to increase milk yield and the proportion
      of unsaturated fatty acids in milk fat.

PMID- 8872719
TI  - Effect of fungal biomass in moldy alfalfa hay on preference by dairy calves with
      no previous exposure to moldy feeds.
AB  - A study of 141-kg dairy calves evaluated their preference for alfalfa hay that
      contained different amounts of fungal biomass, which was estimated by the
      glucosamine assay. Alfalfa that was harvested at different maturities and stored
      at varying DM contents was chopped and blended to produce four forage treatments.
      The four forage treatments included hay that had 1) low NDF content and a low
      amount of fungal biomass, 2) high NDF and low fungal biomass, 3) high NDF and
      moderate fungal biomass, and 4) high NDF and high fungal biomass. Forage
      treatments were offered in pair combinations with two feeders per calf;
      treatments were switched from one feeder to the other on alternate days. The four
      forage treatments were offered in such a way that all six pair combinations were
      tested in each period. Each of the two trials was designed as a 6 x 6 Latin
      square. Preference data were collected for the 6-d periods and were analyzed as a
      split plot. Difference in intake of paired forage treatments was the response
      variable. Hay preference declined as either fiber content of hay or amount of
      fungal biomass in hay increased. Forage intake of each treatment relative to mean
      intake was 3.3, 0.8, -0.5 and -3.7 kg/6 d for forage treatments 1, 2, 3, and 4,
      respectively. Low preference for molded hay would probably result in greater feed
      sorting and lower intakes when calves have a choice of feedstuffs.

PMID- 8872720
TI  - Effect of plane of nutrition before and after 200 kilograms of body weight on
      mammary development of prepubertal Holstein heifers.
AB  - Twenty Holstein heifer calves at 138 d of age and 118 kg of BW were assigned
      randomly to one of four treatments in a factorial design. Heifers were fed for
      low (0.7 kg/d) or high (> 1.0 kg/d) gain during two periods. Period 1 was from
      start to 200 kg of BW, and period 2 was from 200 kg of BW to slaughter, which
      occurred in the middle of the luteal phase following the third estrus. Calves on
      the high plane of nutrition during period 2 were heavier at the end of trial and
      gained more BW between puberty and the end of trial. Those calves also had
      heavier mammary glands, which had more fat and dry fat-free tissue. Heifers that
      had been raised on the low plane of nutrition throughout the trial had greater
      concentrations of DNA and RNA but did not have greater protein in the dry fat
      free tissue. Low plane of nutrition during either period increased DNA and RNA
      concentration in the dry fat-free tissue. Total mass of DNA and RNA did not
      differ among treatments. Protein mass was increased by the high plane of
      nutrition during period 2. This study indicated that dietary manipulation affects
      mammary dry fat-free tissue, protein, and adipose mass in the period up to and
      including puberty.

PMID- 8872721
TI  - Evaluation of wheat gluten in milk replacers and calf starters.
AB  - Two trials were conducted to evaluate wheat gluten as an ingredient in calf
      feeds. In one trial, Holstein bull calves (n = 120) were assigned for 6 wk to one
      of five milk replacers, which contained different percentages of CP and different
      percentages of protein furnished from soluble wheat gluten. Within a given
      protein percentage, BW gains of calves were not affected by the percentage of
      protein that was supplied as wheat gluten. Calves fed milk replacer containing
      18% CP with 33% wheat gluten gained as much as calves fed replacers containing
      20% CP. In another trial, newborn Holstein calves (n = 62) were used. Protein
      supplements of the calf starters used until 7 wk of age were either soybean meal
      or spray-dried wheat gluten and soybean meal. No significant differences were
      observed between the two treatments. Also, no significant carry-over effect
      occurred when all calves received a common diet from 7 to 10 wk of age.

PMID- 8872722
TI  - Plasma lipoproteins in preruminant calves fed diets containing tallow or soybean
      oil with and without cholesterol.
AB  - Five-week-old, preruminant male calves were fed milk replacer containing tallow
      or soybean oil (230 g/ kg of dietary DM) with and without cholesterol (10 g/ kg
      of dietary DM) for 17 d in order to study changes in plasma lipids and
      lipoproteins. Dietary soybean oil induced higher cholesterolemia than did tallow
      because of a specific increase in plasma concentrations of large high density
      lipoproteins of type 1 (1.026 to 1.060 g/ml), but plasma concentrations of low
      and very low density lipoproteins were not modified. Addition of cholesterol to
      diets containing either tallow or soybean oil markedly increased plasma
      concentrations of intermediate and low density lipoproteins, suggesting partial
      inhibition of the low density lipoprotein receptor activity in tissue. By
      contrast, dietary cholesterol added to the diet containing soybean oil led to an
      increase in plasma concentrations of type 1 high density lipoproteins and of
      light high density (1.060 to 1.091 g/ml) lipoproteins. These data indicated that
      the soybean oil diet, which was rich in linoleic acid, did not reduce the effects
      of dietary cholesterol on the metabolism of low and high density lipoproteins in
      the preruminant calf.

PMID- 8872723
TI  - Immune response and disease resistance of calves fed chromium nicotinic acid
      complex or chromium chloride.
AB  - Twenty-one Holstein bull calves (< 7 d of age at the initiation of the
      experiment) fed a milk replacer diet were used to assess the effects of
      supplemental Cr on immune response. Treatments consisted of milk replacer without
      supplemental Cr (control) or milk replacer with 0.4 ppm of supplemental Cr from
      CrCl3 or a Cr-nicotinic acid complex. On d 64, increases in skinfold thickness
      after an intradermal injection of phytohemagglutinin were measured to evaluate
      cell-mediated immune response. Calves supplemented with Cr-nicotinic acid complex
      had a greater response than did controls at 6, 12, 24, and 48 h after injection.
      Calves supplemented with CrCl3 had a greater response than did controls at 24 and
      48 h after injection. In vitro blastogenic responses of lymphocytes to
      phytohemagglutinin or pokeweed mitogen and antibody response to porcine red blood
      cells were not affected by treatment. Following a disease challenge with an
      intranasal dose of infectious bovine rhinotracheitis on d 75, body temperature
      tended to be lower for calves supplemented with Cr-nicotinic acid complex than
      for control calves. Calves supplemented with either Cr source had lower serum
      cortisol concentrations at 5 d after challenge. Chromium supplementation enhanced
      cell-mediated immune function.

PMID- 8872724
TI  - Relationships between clinical mastitis, somatic cell score, and production for
      the first three lactations of Finnish Ayrshire.
AB  - Data on 23,196 cows were extracted from the Finnish system for recording health
      data and merged with information on SCS and 305-d milk production to study 1) the
      genetic and phenotypic correlations of clinical mastitis (within 150 d
      postpartum) and SCS across the first three lactations and 2) the genetic
      relationships between the traits for individual lactations. (Co)variance
      components were estimated using linear multitrait REML and the expectation
      maximization algorithm. Heritability estimates for separate lactations were
      distinctly higher for somatic cell score (0.14 to 0.19) than for clinical
      mastitis (0.02 to 0.05). Genetic correlations of the same traits among different
      lactations were positive and moderate to high, suggesting that, in practice,
      clinical mastitis and SCS can be considered as the same traits for different
      lactations. Genetic correlations of clinical mastitis and SCS varied from 0.37
      for first lactation to 0.68 for third lactation, implying that clinical mastitis
      and SCC monitor different aspects of udder health. A clear, antagonistic genetic
      association existed between clinical mastitis and milk production, but the
      genetic correlation of SCS and milk production did not differ from 0.

PMID- 8872725
TI  - Economic viability of crosses of Bos taurus and Bos indicus for dairying in warm
      climates.
AB  - Countries in the warm climatic zones need greater domestic supplies of milk. To
      increase yields, the option that is least expensive and most widely used is to
      cross dairy breed sires with local cattle. First generation crosses have more
      vigor than other crosses under stressful environmental conditions; growth rate,
      milk yield, and reproduction rate exceed those of local breeds and other
      crossbred combinations. On average, lactating first generation crosses are fed
      energy at 45 to 60% below their potential response, which limits their
      capabilities. Other crosses with local breeds fall short of first generation
      crosses as do some of the present synthetic breeds with 5/8 to 3/4 dairy
      breeding. Well-fed (> 2.5 maintenance needs) Holstein or Jersey crosses
      containing 1/4, 1/2, or 3/4 Bos indicus (Zebu) tend to follow projections of
      parental means for milk yield, reproduction rate, and tolerance to heat stress;
      however, for crosses, losses exceed predictions for lactation length, persistency
      of milk yield, feed efficiency, and rate of milking. Size of thoracic and
      abdominal organs, size of endocrine glands, stomach weight, and intestine length
      are lower than expected compared with values for purebreds. The smaller digestive
      system affects feeding intake of B. indicus crosses, and the smaller endocrine
      glands appear to limit responses to high energy diets. Possible directional
      dominance of B. indicus needs further investigation. The first generation crosses
      could support their use for dairy purposes if feeding rate and management were
      optimal, but prospects for other crosses remain questionable.

PMID- 8872726
TI  - Comparison of acucise endopyelotomy and endoballoon rupture for management of
      secondary proximal ureteral stricture in the porcine model.
AB  - At this point in time, endopyelotomy is first-line therapy for both primary and
      secondary adult ureteropelvic junction obstruction (UPJO) in many medical
      centers. However, the potential, albeit small, for significant bleeding with any
      endoincision of the UPJ has sparked interest in the simple, less morbid technique
      of endoballoon rupture. To date, no comparative data are available on the
      effectiveness of these two techniques. Thirty female minipigs were randomized to
      cutting balloon (Acucise) endopyelotomy (AEP) (N = 13), endoballoon rupture (EBR)
      (N = 13), or a control arm (N = 4). Following baseline retrograde pyelogram (RPG)
      and diuretic renogram (DRG), a secondary proximal ureteral stricture was created
      by laparoscopic ligation of the UPJ. After 8 weeks, AEP or EBR was performed in
      each of the study pigs. In 16 pigs (8 AEP, 8 EBR), a 7F 22-cm ureteral stent was
      placed (chronic arm). After 6 weeks, the stent was removed, and a second RPG and
      DRG were performed. Three months post-treatment, after RPG and DRG, the renal
      units were harvested, and histologic sections of the affected UPJ, contralateral
      normal ureter, and ipsilateral kidney were examined. Ten pigs (5 AEP, 5 EBR)
      underwent harvest immediately after treatment (acute arm). The four control
      animals remained untreated. At 8 weeks, all minipigs had obstructive findings on
      RPG and DRG. All UPJs could be treated but one, which had an impassable
      stricture; there were no perioperative complications. In the acute arm, all UPJs
      were patent. All five AEP ureters had evidence of an uneven cut and cautery
      effect. Of the EBR ureters, two had smooth tears and three had ragged tears, and
      none had evidence of cautery effect. In the chronic arm, 3 months after either
      AEP or EBR, all minipigs had a patent UPJ, yet only 5 of 16 had an improved 1 1/2
      by DRG. Histologic sections of the affected UPJs from 20 minipigs in the chronic
      arm (8 AEP, 8 EBR, 4 controls) were indistinguishable among the three groups;
      each revealed significant periureteral fibrosis and chronic inflammation with a
      mainly unremarkable muscular layer. However, histologic sections of 25 treated
      kidneys, including both acute and chronic animals (13 AEP, 12 EBR), revealed
      endstage renal disease (N = 10), chronic inflammatory changes (N = 7), or normal
      tissue (N = 8). Again, there was no trend favoring either AEP and EBR. In
      summary, in this laboratory study, we could detect no difference in outcome
      between an incisional endopyelotomy and an endoballoon rupture for treating
      secondary UPJO.

PMID- 8872727
TI  - Carbon dioxide homeostasis during transperitoneal or extraperitoneal laparoscopic
      pelvic lymphadenectomy: a real-time intraoperative comparison.
AB  - The primary goal of this study was to evaluate differences in carbon dioxide
      metabolism between patients undergoing transperitoneal or extraperitoneal
      laparoscopic pelvic lymph node dissection (L-PLND) for staging of adenocarcinoma
      of the prostate (CaP). Eighteen candidates undergoing L-PLND were divided between
      the transperitoneal (N = 12) and extraperitoneal (N = 6) approaches. End-tidal
      partial pressure of CO2 (PeCO2) and minute volume of expired CO2 (VCO2) were
      considered indicators of CO2 absorption. These two parameters were monitored
      intraoperatively utilizing a metabolic cart and Ohmeda Rascal-II. The
      cardiostimulatory effect of increasing serum CO2 and the ventilatory
      countermeasures used to correct the iatrogenic hypercapnia associated with CO2
      insufflation were also measured. With the exception of the region of CO2
      insufflation, the operative procedure and perioperative care were identical for
      the two groups. Preoperative patient characteristics were similar. The mean time
      of CO2 insufflation was 136 minutes for the transperitoneal group and 120 minutes
      for the extraperitoneal group. The absorption of CO2 was significantly greater
      and more rapid during extraperitoneal L-PLND. This may be attributable to more
      profound CO2 absorption from the parietal peritoneal surface compounded by
      subcutaneous CO2 emphysema. Disruption of microvascular and lymphatic channels
      during the development of the extraperitoneal working space facilitates direct
      CO2 absorption into the intravascular space. A minor increase in heart rate and
      systolic blood pressure was noted during CO2 insufflation. In all but one patient
      (extraperitoneal group), hypercarbia and acidemia were prevented by an increased
      ventilatory rate. The potential dysrhythmogenicity of hypercarbia may
      contraindicate the extraperitoneal approach in patients with cardiopulmonary
      disease.

PMID- 8872728
TI  - Effect of extracorporeal shockwave lithotripsy on plasma and urine endothelin
      concentrations.
AB  - Since the first reports of extracorporeal shockwave lithotripsy (SWL), there have
      been increasing numbers of articles in the literature documenting renal blood
      flow impairment and blood pressure elevation as complications. However, little is
      known about the pathophysiology and prevention of these complications. In this
      prospective study, the influence of high-energy shockwaves on plasma and urine
      endothelin concentrations was investigated in 20 patients with renal stones. The
      patients were randomly assigned to receive a calcium channel blocker, 10 mg of
      nitrendipine (Bypress; Bayer) (N = 10) 2 hours before SWL or no medication
      (control group; N = 10). Blood samples were taken just before and 1 minute after
      application of 3000 shocks. Urine samples were collected by ureteral catheters.
      The plasma endothelin-1 concentrations were significantly elevated after SWL in
      the control group (P = 0.003). On the other hand, nitrendipine significantly
      reduced plasma endothelin concentrations after SWL (P = 0.003). No significant
      change was observed in urine samples and blood pressure measurements. These
      results suggest that endothelin release after SWL may be a cause for lithotripsy
      induced hemodynamic changes. Medical prevention with calcium channel blockers
      warrants further investigation.

PMID- 8872729
TI  - Protective effect of verapamil on renal tissue during shockwave application in
      rabbit model.
AB  - Although extracorporeal shockwave lithotripsy (SWL) is the treatment of choice
      for symptomatic urinary calculi, it has been shown in number of studies that
      adverse effects of high-energy shockwaves may be encountered in short- and long
      term follow-up. To evaluate the possible protective effect of verapamil
      administration on renal tissue, both magnetic resonance imaging (MRI) and
      histopathologic examination were performed after SWL in rabbits. Thirty-five
      animals were divided into three groups. The 15 animals in the first group were
      fed verapamil (0.1 mg/kg) for 3 days. Another 15 animals received no medication
      but underwent SWL, and the remaining 5 animals received anesthesia alone (sham
      group). The animals were then subdivided into three groups according to the
      shockwave number applied (1000, 15,000, or 2000) and the aforementioned
      evaluations were performed 24 hours and 3 months after the procedure. We found
      prominent histopathologic alterations in animals not receiving any medication
      before SWL. Persistence of these pathologic alterations during 3 months of follow
      up indicated the importance of preservation of renal architecture during high
      energy shockwave application. On the other hand, animals under verapamil
      medication prior to SWL demonstrated only a limited degree of histopathologic
      alteration. Demonstration of a normal histologic pattern after 3 months supported
      the preservation of tissue structure by such medication. No significant
      histopathologic alteration could be observed in the sham-group animals, as
      expected. Our study demonstrates that verapamil is protective against shockwave
      induced renal tubular damage. Such medications may be useful to avoid the proven
      histopathologic and functional side effects of high-energy shockwaves.

PMID- 8872730
TI  - Use of image enhancement during lithotripsy.
AB  - Renal excursion during breathing is inevitable and is a cause of poor
      localization during extracorporeal shock-wave lithotripsy (SWL), which in theory
      might lead to poor treatment results. Eighty-one patients underwent lithotripsy
      treatment with and without the use of an image enhancement system designed for
      use with the Dornier MPL9000 lithotripter. This device contains a memory
      incorporated into a separate differential grayscale monitor, which allows the
      stone image to be stored. Shockwave release is enabled only when this image
      corresponds to the real-time image on the lithotripter ultrasound monitor. No
      improvement in success rates was found using this system, although upper-pole
      stones appeared to be fragmented more successfully. Overall, the results were
      favorable in both groups after a single treatment. Further work is needed to
      establish whether image enhancement is capable of improving the success rates and
      reducing the side effects of lithotripsy by better targeting.

PMID- 8872731
TI  - Outcome assessment of double-J stents during extracorporeal shockwave lithotripsy
      of small solitary renal calculi.
AB  - The utility of indwelling double-J ureteral stents during extracorporeal
      shockwave lithotripsy (SWL) of renal calculi is ill defined. We evaluated 179
      patients treated with SWL for small (< 20 mm in diameter) solitary renal calculi
      with (N = 27) or without (N = 152) indwelling ureteral stents. There was no
      significant difference in the stone-free rates at 1 month (both 52%) and 3 months
      (61% nonstented group v 67% stented group; P = 0.45) or in the retreatment rates
      (13.3% nonstented group v 14.8% stented group; P = 0.60). The incidence and
      severity of pain/renal colic were similar for the two treatment groups. There was
      minimal morbidity associated with SWL in either group. Placement of double-J
      stents for the purpose of improving stone-free rates, alleviating pain, or
      preventing ureteral obstruction in conjunction with SWL of solitary renal calculi
      < 20 mm in diameter is unnecessary.

PMID- 8872733
TI  - Retrograde ureteral intussusception: a rare complication.
AB  - A 45-year-old man with a history of cyclophosphamide exposure underwent repeated
      ureteroscopy for positive urine cytology findings after resection of a Grade 2
      papillary transitional-cell carcinoma of the bladder. Despite careful technique,
      an intussusception developed in the left ureter, which was repaired by resection
      and construction of a Boari flap. To our knowledge, this is the first report of
      retrograde ureteral intussusception caused by ureteroscopy.

PMID- 8872732
TI  - Role of lasertripsy in the management of ureteral calculi: experience with
      alexandrite laser system in 232 patients.
AB  - In 232 patients with ureteral stones, lasertripsy was used as primary treatment
      or as second-line therapy after extracorporeal shockwave lithotripsy (SWL). In
      all patients, a semirigid 6.5F ureteroscope or a flexible 6F ureteroscope was
      used. Lithotripsy was performed employing an alexandrite laser with an energy of
      50 to 65 mJ. The immediate success rate was 67.5% for stones in the upper ureter,
      86.1% for those in the midureter, and 94.5% for those in the distal ureter. In
      16.5% of the treatments, it was necessary to insert a double-J stent. A
      perforation of the ureter happened in two patients (0.9%), but no laser-related
      complications were seen. Stone fragmentation was not dependent on stone
      composition or size. Using small semirigid or flexible ureteroscopes, lasertripsy
      of ureteral stones is a minimally invasive treatment with an insignificant
      complication rate. In case of midureteral stones, our results revealed a higher
      immediate stone-free rate than is reported in the literature after treatment by
      SWL, and we can therefore recommend lasertripsy as primary treatment. For upper
      ureteral stones, lasertripsy can be recommended as a helpful auxillary procedure.
      Furthermore, in cases of distal ureteral stones, lasertripsy challenges SWL as
      the primary treatment.

PMID- 8872734
TI  - Comparative financial analysis of laparoscopic pelvic lymph node dissection
      performed in 1990-1992 v 1993-1994.
AB  - In 1994, it was reported that laparoscopic pelvic lymph node dissection (L-PLND)
      was US $1350 more expensive than open pelvic lymph node dissection (O-PLND) for
      the staging of prostate cancer. Despite the lower postoperative expenses
      associated with L-PLND, the intraoperative expenditures were 52% higher,
      primarily because of the prolonged operating time and the cost of disposable
      instrumentation. The objective of the present study was to determine if, with
      increasing laparoscopic experience and a more competitive surgical supply market,
      the intraoperative as well as the overall hospital expenses would diminish. The
      study population consisted of 105 men who underwent staging L-PLND for cancer of
      the prostate. Group I was composed of 50 patients who underwent surgery between
      1990 and 1992, and Group II consisted of 55 patients operated on in 1993 and
      1994. All hospital-related expenses were reorganized into preoperative,
      intraoperative, and postoperative and subsequently corrected for inflationary
      changes to a base year of 1993-1994. The total overall expenses of the two groups
      were similar, differing by only $65. Despite a lowering of preoperative and
      postoperative expenses in the 1993-1994 group by 112% and 31%, respectively, the
      intraoperative expenses were still $571 higher. The operative time decreased by
      19 minutes in the contemporary group, but the expense of surgical supplies
      continued to increase up to $910 (104%) more than the 1990-1992 group. It is
      hoped that the use of "laparoscopic kits" as well hospital equipment consortiums
      will help slow the escalating costs of surgical care. However, it is the
      responsibility of the laparoscopic surgeon to demonstrate that these procedures
      are as safe, efficient, and cost-effective as their open counterpart.

PMID- 8872735
TI  - Laparoscopic adrenalectomy via the retroperitoneal approach: first five cases.
AB  - Between February and November 1994, we performed laparoscopic retroperitoneal
      adrenalectomy in five patients with benign adrenal tumors to confirm the efficacy
      of this operation. Using digital dissection and a balloon, we created a working
      space in the retroperitoneal cavity before we dissected the adrenal gland and
      removed it under laparoscopic observation. The adrenal glands of all five
      patients were removed without any complications. The mean operative time was 3.4
      hours, and the mean estimated blood loss was 148 mL. The average postoperative
      hospital stay was 10 days, and the average full recovery time was 19 days. We
      concluded that the retroperitoneal approach is an advantageous and safe procedure
      in the laparoscopic removal of the adrenal gland with benign tumor.

PMID- 8872736
TI  - Laparoscopic repair of enterocele.
AB  - The repair of an enterocele has classically been via a transvaginal or open
      abdominal route. With the availability of minimally invasive procedures, we
      applied established laparoscopic techniques to enterocele repair. Three women
      with a history of hysterectomy had a symptomatic enterocele as well as a
      cystocele or rectocele. Each underwent a transperitoneal laparoscopic enterocele
      repair prior to a transvaginal rectocele or cystocele repair or laparoscopic
      colposuspension. Using three trocars and transvaginal digital manipulation, the
      enterocele was reduced and repaired utilizing a modified Moschocowitz technique.
      The cul-de-sac was obliterated by approximating the posterior vaginal fascia to
      the anterior wall of the rectum with a running suture. There was no operative
      morbidity. The average length of stay was 3.3 days. All patients were
      asymptomatic with no enterocele recurrence identified during a mean follow-up of
      10.5 (range 7-15) months. Laparoscopic enterocele repair is a feasible surgical
      procedure with minimal morbidity. A larger series with longer follow-up is
      necessary before the efficacy and proper indications for this minimally invasive
      procedure are determined.

PMID- 8872737
TI  - Comparison of three-dimensional and two-dimensional laparoscopic video systems.
AB  - The limitations of two-dimensional (2D) video may be overcome by the recent
      introduction of the three-dimensional (3D) laparoscope and video system. Twenty
      two urologic and gynecologic surgeons experienced in laparoscopy were evaluated
      during a live porcine laboratory session in an advanced course designed to teach
      laparoscopic retroperitioneal nephrectomy and bladder neck suspension. The
      surgeons performed dissection of the kidney, securing of the renal vessels,
      laparoscopic suturing and intracorporeal knot-tying at the bladder neck, and
      suture clipping of an intracorporeally placed suture at the bladder neck using 2D
      and 3D equipment. The time needed to complete each technique was recorded and
      compared using nonparametric analysis. The participants' subjective evaluation of
      the 3D system was also analyzed. Three-dimensional video did not significantly
      improve the surgeons' ability to perform laparoscopic dissection of the kidney,
      securing the renal vessels, or laparoscopic suturing and knot-tying. Surgeons
      felt that the 3D system did not improve vision or perceived surgical performance
      sufficiently to justify an expense greater than that of the 2D systems now
      available. Compared with the standard 2D camera system, the currently available
      3D video system does not hasten the laparoscopic dissection of tissues or the
      performance of advanced technical maneuvers such as laparoscopic suturing and
      knot-tying by experienced laparoscopists.

PMID- 8872738
TI  - Complications of extraperitoneal balloon dilation.
AB  - The success of balloon dissection techniques has given laparoscopic surgeons the
      option of a direct extraperitoneal approach to urologic disease. Unfortunately,
      these techniques are not without risks. We report on four cases of complications
      secondary to balloon dilation. In two instances, balloon misplacement caused
      dissection between muscle layers. This resulted in conversion to an open
      procedure in one instance and to a postoperative flank hernia in another. Balloon
      rupture with loose fragments occurred in two patients. In one of these cases, the
      peritoneum was lacerated, with balloon fragments displaced within the peritoneal
      cavity.

PMID- 8872739
TI  - Value of laparoscopy in the management of calculi complicating renal
      malformations.
AB  - A minimally invasive approach for urolithiasis patients with complex anatomic
      abnormalities occasionally necessitates the use of laparoscopic techniques,
      either alone or in combination with endourologic techniques. The management of
      these patients is best accomplished in centers with the facilities to provide a
      spectrum of endourologic and laparoscopic techniques. Two illustrative cases are
      described.

PMID- 8872740
TI  - Endourethrotomy of posterior urethral obliterations and severe strictures:
      improved outcome with urethral self-dilatation.
AB  - Eighteen male patients underwent endoscopic management of urethral obliterations
      and severe strictures of the subprostatic urethra. Thirteen patients who
      performed clean urethral self-dilatation after endoscopic repair had a lower
      incidence of recurrent strictures (P = 0.03) and required fewer visual internal
      urethrotomies than the initial five patients, who did not self-dilate (P = 0.01).
      All patients had minimal morbidity and required short hospitalization to achieve
      adequate urine flow and a stable urethral neolumen during the follow-up period.

PMID- 8872741
TI  - Visual laser coagulation of the prostate using intraurethral gel anesthesia and
      light intravenous analgesia and sedation.
AB  - Twenty-eight patients with symptomatic bladder outlet obstruction secondary to
      benign prostatic hyperplasia were treated as outpatients by visual laser
      coagulation of the prostate using only intraurethral gel anesthesia and light
      intravenous sedation and analgesia. No premedication was administered. Laser
      coagulation was performed with the Myriadlase side-firing fiber using a standard
      Sharplan neodymium: YAG laser source at 40 W power setting, and 650 (516-1000)
      J/g of prostate tissue was delivered. Patient acceptance was favorable. All
      remained relaxed, cooperative, and without pain during the procedure. None of the
      patients required any further anesthesia. There was no significant change in
      blood pressure, pulse rate, or peripheral oxygen saturation measurements during
      the procedure. Any patient who feels comfortable with a diagnostic cystoscopy
      being performed using intraurethral gel anesthesia should find this anesthesia
      protocol acceptable for laser coagulation of the prostate.

PMID- 8872742
TI  - Structure-activity studies on monoamine oxidase inhibitors by calorimetric and
      quantum mechanical calculations.
AB  - Structure-activity relationship studies were carried out on a new series of
      hydrazino-thiosemicarbazide derivatives, which inhibit monoamino oxidase (MAO).
      Fifty-five compounds were synthesized and tested "in vitro" for their inhibitory
      effects on rat liver mitochondrial MAO. The most efficient MAO inhibitors were
      the benzylidene derivatives (sequence: see text] where R is the piperonyl radical
      and ethyl or isopropyl substituents are in R1 position. Correlation of MAO
      activity with hydrophobic, electronic and steric properties of tested compounds,
      evaluated by means of Quantum Mechanical calculations and calorimetric analysis
      (DSC) suggest that electronic and steric parameters give a better fit than
      hydrophobicity with the biological activity.

PMID- 8872744
TI  - Kinetics of the course of inactivation of yeast alcohol dehydrogenase by 4-(2
      pyridylazo)-resorcinol.
AB  - The kinetic theory of the substrate reaction during modification of enzyme
      activity previously described by Wang and Tsou has been applied to a study on the
      kinetics of the course of inactivation of alcohol dehydrogenase by 4-(2
      pyridylazo)-resorcinol (PAR). The results showed that the inhibition of this
      enzyme by PAR was irreversible. A plot of 1n([P] infinity -[P]) versus give a
      straight line, suggesting that the inactivation kinetic course is monophasic. The
      kinetic analysis of the substrate reaction with different concentrations of the
      substrate and the inactivator has shown that the inactivation of yeast alcohol
      dehydrogenase by PAR involves complex formation, and that the substrate ethanol
      competes with PAR at the active site of the enzyme. The dissociation constants
      between the substrates and the enzyme as well as the microscopic rate constants
      for the inactivation of the enzyme have been determined.

PMID- 8872743
TI  - Sanguinarine and chelerythrine as inhibitors of aromatic amino acid
      decarboxylase.
AB  - Quaternary benzo[c]phenanthridine alkaloids sanguinarine, chelerythrine and their
      dihydroderivatives were tested as inhibitors of aromatic amino acid decarboxylase
      (EC 4.1, 1.28, AAD) from rat liver. Sanguinarine and chelerythrine exhibited
      strong inhibition of AAD with Ki 1.2 x 10(-4) M and 5.8 x 10(-4) M, respectively,
      while no inhibitory effect was observed for their dihydroderivatives. The
      inhibition was found to be irreversible. The enzyme-inhibitor interaction
      apparently stabilized AAD against thermal inactivation. Pyridoxal-5'-phosphate
      partially decreased but did not reverse the inhibition. Dithiothreitol prevented
      the inhibitory effect of sanguinarine and chelerythrine which indicates that the
      interaction with thiol groups essential for AAD activity is included in the
      inhibition mechanism.

PMID- 8872745
TI  - Comparison of kinetic properties between plant and fungal amine oxidases.
AB  - Kinetic properties of novel amine oxidases isolated from a mold Aspergillus niger
      AKU 3302 were compared to those of typical plant amine oxidase from pea seedling
      (EC 1.4.3.6). Pea amine oxidase showed highest affinity with diamines, such as
      putrescine and cadaverine, while fungal enzymes oxidized preferably n-hexylamine
      and tyramine. All enzymes were inhibited by carbonyl reagents, copper chelating
      agents, some substrate analogs and alkaloids, but there were quite significant
      differences in the sensitivity and inhibition modes. Aminoguanidine, which
      strongly inhibited pea amine oxidases showed only little effect on fungal
      enzymes. Substrate analogs such as 1.5-diamino-3-pentanone and 1-amino-3-phenyl-3
      propanone, which were potent competitive inhibitors of pea amine oxidases,
      inhibited fungal enzymes much more weakly and non competitively. Also various
      alkaloids behaving as competitive inhibitors of pea amine oxidase inhibited the
      fungal enzymes non competitively. Very surprising was the potent inhibition of
      fungal enzymes by artificial substrates of pea amine oxidases, E- and Z-1,4
      diamino-2-butene. The relationships between the different inhibition modes and
      possible binding at the active site are discussed.

PMID- 8872746
TI  - Inhibition of camel lens zeta-crystallin/NADPH:quinone oxidoreductase activity by
      Cibacron blue.
AB  - Camel lens zeta-crystallin/NADH:quinone oxidoreductase activity was inhibited by
      Cibacron blue 3GA (CB) with 9.10-phenanthrenequinone (PQ) as an electron acceptor
      and NADPH as an electron donor in a time-independent and concentration dependent
      manner. The IC50 value of CB was 50 nM. The Lineweaver-Burk plots and the
      secondary plots indicated that the inhibition was linear mixed type (partial
      competitive and pure noncompetitive) with respect to NADPH and noncompetitive
      with respect to PQ. The estimated inhibition constant (Ki) values were 26.0 nM
      for NADPH and 55.0 nM for PQ respectively, suggesting that CB has high affinity
      towards the NADPH binding site. The secondary plots of inhibition with respect to
      NADPH, also indicate a dissociation constant (Ki) value of 68.0 nM for the zeta
      crystallin-NADPH-CB complex. This Ki being greater than the Ki value suggests
      that noncompetitive inhibition is predominant over competitive inhibition at the
      NADPH binding site.

PMID- 8872747
TI  - Inhibition of DNA methyltransferase by microbial inhibitors and fatty acids.
AB  - Streptomyces sp. strain No. 560 produces four kinds of DNA methyltransferase
      inhibitors in the culture filtrate. One of them, DMI-4 was distinguished from DMI
      1, -2 and -3 previously reported with respect to certain properties, DMI-4 is
      considered to be a triglyceride consisting of the fatty acids
      anteisopentadecanoic acid (C15:0), isopalmitic acid (C16:0) and isostearic acid
      (C18:0) from the results of gas chromatography analysis. Since DMI-4 contains
      three molecules of fatty acid, and the previously reported DMI-1, 8
      methylpentadecanoic acid, is analogous to a fatty acid, the inhibitory activity
      has been examined of various fatty acids and their methyl esters against Eco RI
      DNA methyltransferase (M. Eco RI). Oleic acid (C18:1) was found to be a potent
      inhibiton of M. Eco RI. The inhibitory activity of oleic acid was shown to be pH-
      and temperature-dependent and inhibited M. Eco RI in a noncompetitive manner with
      respect to DNA or S-adenosylmethionine (SAM). The number of carbon atoms and
      double bonds in the fatty acid molecule affected the inhibitory activity, but
      their methyl esters were not inhibitors. Our results suggest that the length of
      the carbon chain, the number of double bonds and the presence of a carboxyl group
      and branched methyl group in the fatty acid molecule may play an important role
      in the inhibition of DNA methyltransferase.

PMID- 8872748
TI  - Interaction of tissue plasminogen activator inhibitor with cell surface
      guanidinobenzoatase and urokinase plasminogen activator.
AB  - This study employs fluorescent inhibitor molecules to detect both cell surface
      proteases and their receptor sites on colonic carcinoma cells. Present studies
      are concerned with the interactions of the tumour associated proteases,
      guanidinobenzoatase (GB) and plasminogen activators (PAs) with PAs inhibitor type
      1 (PAI-1). The active enzymes on the cell surfaces in frozen sections of human
      colonic carcinoma tissue were located by staining with two active site directed
      fluorescent inhibitors, 9-aminoacridine (9-AA) and Rhodamine labelled PAI-1 (Rh
      PAI-1), followed by fluorescence microscopy. Fibrin treated sections, which now
      lack GB but have receptor proteins for GB, fail to bind 9-AA and Rh-PAI-1. When
      these fibrin-treated sections were incubated with purified colonic carcinoma GB
      and u-PA, both enzymes were bound to the tumour cells in these sections and
      subsequent challenging with fluorescent probes for GB resulted in bright
      fluorescence under appropriate microscopic conditions. On the other hand when
      fibrin treated sections were incubated with t-PA, followed by challenging with Rh
      PAI-1, no red fluorescence was observed. It is suggested that the GB and u-PA
      have similar specific binding sites which can recognise and bind to the receptors
      on tumour cells in fibrin-treated sections, but t-PA has no such binding site and
      fails to recognise the cell surface receptors for GB. These GB-receptors may have
      a possible role in the regulation of GB and u-PA activity during tumour cell
      invasion and metastasis.

PMID- 8872749
TI  - Leukocytosis is a poor indicator of acute osteomyelitis of the foot in diabetes
      mellitus.
AB  - The purpose of this article is to describe the frequency of leukocytosis and
      elevated erythrocyte sedimentation rate in a series of diabetics with acute foot
      infections and osteomyelitis due to neuropathic foot ulcerations. The authors
      reviewed the admission records of 28 type II diabetic patients admitted to
      University Hospital in San Antonio, Texas between January 1, 1990 and December
      30, 1992 with acute osteomyelitis of the foot secondary to neuropathic
      ulceration. The mean white blood cell count on admission for all subjects studied
      was calculated at 11.9 +/- 5.4 x 10(3) cells/mm3. Of all white blood cell counts
      collected for patients admitted with acute osteomyelitis of the foot, 54% were
      within normal limits. Erythrocyte sedimentation rate was elevated in 96% of
      patients. Oral temperature was normal in 82% of patients. The authors conclude
      that a normal white cell count should not deter one from taking appropriate
      action to mitigate the propagation of a potentially limb-threatening foot
      infection.

PMID- 8872750
TI  - Complex regional pain syndrome.
AB  - Reflex sympathetic dystrophy is a complex progressive and potentially devastating
      condition generally affecting the extremities. Because clinical presentation is
      variable, diagnosis can be difficult. Recently, the Special interest Group of
      Pain and the Sympathetic Nervous System of the International Association for the
      Study of Pain developed a new taxonomy to help acknowledge and differentiate the
      features of reflex sympathetic dystrophy and causalgia. These are categorized
      under the heading of complex regional pain syndrome. Sympathetically maintained
      pain is also recognized as a separate component to this group of conditions. The
      authors present this new taxonomy and present cases of each condition.

PMID- 8872751
TI  - Psoriasis and elective foot surgery.
AB  - The authors present a brief overview of the dermatologic condition, psoriasis.
      Special attention is given to a review of the literature as it addresses surgery
      and the psoriatic patient. The authors conclude that psoriatic patients are
      somewhat more susceptible to postoperative infection, but with proper
      precautions, complications can be avoided. Therefore, the condition of psoriasis
      is not an absolute contraindication to elective foot surgery.

PMID- 8872752
TI  - The hallucal interphalangeal sesamoid.
AB  - The hallucal interphalangeal sesamoid is considered by some to represent an
      anatomical rarity that possesses little clinical significance. However, the
      location of this seemingly innocuous sesamoid bone directly inferior to the
      hallucal interphalangeal joint of the hallux is associated with the development
      of several important anatomical, biomechanical, and clinical pathologies. The
      authors present a review of the literature regarding the location, shape,
      ontogeny, and surgical management of the hallucal interphalangeal sesamoid.
      Additionally, the authors discuss the detrimental effect the hallucal
      interphalangeal sesamoid has on the biomechanical functions of the first
      metatarsophalangeal and hallucal interphalangeal joints.

PMID- 8872753
TI  - Spindle cell hemangioendothelioma: a case presentation and literature review of a
      rare lower extremity tumor.
AB  - The authors present a rare soft tissue mass of the lower extremity that has been
      presented in the podiatric literature only once. Spindle cell
      hemangioendothelioma was first identified 9 years ago, and approximately 45 cases
      have been documented in the literature. This lesion presents as a slow growing
      and often painless lesion of the extremities, with low malignant potential and
      high local recurrence. This patient was treated with surgical excision after a
      mass, which had been present for more than 10 years, began enlarging and became
      painful. A review of the literature and the case presentation will be given.

PMID- 8872754
TI  - Z-bunionectomy: retrospective long-term study.
AB  - Long-term patient satisfaction and objective clinical and radiographic
      examinations of patients who had undergone the Z-bunionectomy at the University
      of Chicago Medical Center were evaluated. Fifty-six surgeries were performed on
      31 patients, with a follow-up range of 5 to 9 years. The University of Maryland
      100-Point Painful Foot Center Scoring System was modified to be more specific to
      bunion surgery, and we used this modification to measure patient satisfaction.
      Patient satisfaction was rated good to excellent by 90% of the patients.
      Radiographic findings included: intermetatarsal angle-mean, 7.1 degrees; hallux
      abductus angle-mean, 8.96 degrees; tibial sesamoid position-mean, 2.8. The mean
      protrusion was -1.64 mm. Radiographic findings consistent with osteonecrosis were
      noted of one patient, one foot, although the patient was clinically asymptomatic.
      The objective findings were as follows: dorsiflexion, mean, 60 degrees;
      plantarflexion, mean, 14 degrees. No patients had pain or crepitus, nor were they
      tract-bound in their first metatarsophalangeal joint range of motion. In
      addition, stance dorsiflexion had a mean of 21 degrees, and the purchase power
      was 88% good to excellent on plantar paper pull-out testing. First ray motion
      qualitatively demonstrated 1 1/2 to 2 times dorsiflexion to plantarflexion. There
      were no subsecond metatarsal head keratoses. Generalized ligamentous laxity was
      not seen. For the resting calcaneal stance position the mean was 3.5 degrees
      everted, with 24% of the patients maximally pronated in this position. We were
      unable to correlate any structural and functional postoperative features with
      patient satisfaction.

PMID- 8872755
TI  - The use of a calcaneal reconstruction plate in intra-articular calcaneal
      fractures.
AB  - Treatment of intra-articular calcaneal fractures has a long and varied history.
      New techniques and application of computerized tomography technology has greatly
      improved the prognosis and is summarized here. A case report with the use of a
      calcaneal reconstruction plate is presented. The authors suggest that in
      comminuted calcaneal fractures that possess a defect in the cancellous bone of
      the calcaneal body, this plate will triangulate fixation over the defect and
      provide for better support of the posterior facet of the subtalar joint.

PMID- 8872756
TI  - Concomitant medial facet and dome fractures of the talus.
AB  - Osteochondral fracture of the dome of the talus is a well known complication of
      an inversion injury of the ankle. Recently the authors encountered a patient
      having a talar dome fracture associated with intra-articular fracture of the
      medial facet after inversion injury of the ankle. The authors have been unable to
      find a medial facet intra-articular fracture reported in the English literature.
      The talar dome fragment was removed arthroscopically and the medial facet
      fragment was removed using an open surgical approach. The mechanism of injury and
      the operative approach are discussed.

PMID- 8872757
TI  - Monitoring neuropathic ulcer healing with infrared dermal thermometry.
AB  - The purpose of this study is to prospectively evaluate skin temperatures at the
      site of neuropathic ulceration before, during, and after wound healing using the
      contralateral extremity as a physiologic control and to evaluate variables that
      may influence skin temperature gradients. We studied 17 male and 8 female
      diabetics with mean age and duration of diabetes of 52.4 +/- 11.6 years and 13.8
      +/- 7.8 years with grade I (Meggitt-Wagner) plantar ulcers. All patients received
      weekly cast changes with wound and skin temperature assessments. After healing,
      all patients were fitted with prescription shoe gear. Temperatures on the
      ulcerated foot were higher than those on the contralateral foot on initial
      presentation (91.1 vs. 84.2 degrees F, t = 8.9, p < 0.0001, 95% Cl 5.3 to 8.5),
      but the same following healing. Patients with vibration perception thresholds
      greater than 45 V had wider skin temperature gradients than those with lesser
      degrees of sensory neuropathy (8.8 +/- 4.1 vs. 4.9 +/- 2.5 degrees F, p = 0.007).
      Additionally, subjects with toe brachial indices below 0.60 had greater skin
      temperature gradients at the site of ulceration than those with higher indices
      (9.4 +/- 4.0 vs. 5.8 +/- 3.4 degrees F, p = 0.01). There was not a significant
      difference in initial skin temperature gradients by duration of wound prior to
      treatment, duration of wound healing, sex, maximum plantar pressure, or
      hemoglobin A1C level.

PMID- 8872758
TI  - Hallux amputation in combination with a lumbar sympathectomy for treatment of a
      non-healing ulceration in a patient with Buerger's disease.
AB  - Buerger's disease is a distal vascular occlusive disease primarily affecting
      those with a history of tobacco use. Treatment of digital pathology can be quite
      difficult as a result. This paper discusses a patient who developed an ulceration
      of the left hallux that did not respond to local wound care and antibiosis. A
      lumbar sympathectomy was performed in conjunction with a hallux amputation to
      promote distal vasodilation and enhance the patient's ability to heal.

PMID- 8872759
TI  - Antibiotic prophylaxis and tourniquet application in podiatric surgery.
AB  - The use of prophylactic antibiosis in podiatric surgery is common, especially in
      patients undergoing endoprosthetic procedures, major arthrodeses, lengthy
      procedures, or in immunocompromised patients. The goal of prophylaxis is to
      prevent infection. For this to occur, there must be an adequate concentration of
      the antimicrobial agent in the tissue at the time of the incision. Historically,
      prophylaxis has consisted of intravenous administration of 1 gm. of cefazolin, 30
      to 60 minutes prior to surgery. Cefazolin concentrations in the medial eminence
      of the first metatarsal were measured in patients undergoing bunionectomy
      procedures where pneumatic ankle tourniquets were used for hemostasis. The goal
      of this study was to determine if the current standards of prophylactic
      antibiotic administration provide adequate bone levels of cefazolin to
      effectively inhibit potential infection-causing pathogens.

PMID- 8872760
TI  - Subcutaneous phaeohypomycosis caused by Scytalidium dimidiatum in the foot of an
      immunosuppressed host.
AB  - The authors present a case report of a subcutaneous phaeohypomycosis of the foot
      in an immuno-suppressed patient. The lesion was caused by Scytalidium dimidiatum,
      a dematiaceous fungus, which has only been reported to cause three previous
      similar lesions. To our knowledge, this is the first reported case of this fungus
      causing a deep-seated mycoses in the United States. A review of the literature
      concerning this organism is also presented.

PMID- 8872761
TI  - The misuse of the Lapidus procedure: re-evaluation of the preoperative criteria.
AB  - Fusion of the metatarsocuneiform joint has been documented in the literature for
      a number of conditions affecting the first ray. The fixation techniques have
      advanced greatly since Lapidus advocated the procedure, but the indications need
      to remain rigid and narrow. The review of the literature illustrates numerous
      complications, and this case presentation specifically depicts the long
      convalescence of the failed fusion of the first metatarsocuneiform joint. The
      Lapidus procedure ultimately should be used as a last resort to eliminate painful
      arthrosis from the metatarsocuneiform joint, reduce severe deformity, or give
      medial column stability to a paralytic or a spastic foot. If no pathology exists
      within the metatarsocuneiform joint, then surgeons should use other procedures to
      correct pathology of the first ray in elective foot surgery.

PMID- 8872762
TI  - Grand rounds: Haglund's deformity and retrocalcaneal, intratendinous spurring.

PMID- 8872763
TI  - Gorhams disease: a literature review and case reports.

PMID- 8872764
TI  - Lymphocyte proliferative responses to recombinant hepatitis C virus antigens in
      patients with chronic hepatitis C.
AB  - The purpose of the present study was to analyse lymphocyte proliferative
      responses to recombinant hepatitis C virus (HCV) antigens in chronic hepatitis C.
      Four recombinant peptides derived from the NS3, core, E1 and E2/NS1 regions of
      the HCV genome were used as antigens in lymphocyte proliferative responses. Forty
      two patients, classified into various sub-groups, and 17 healthy control subjects
      were tested and the specific response was expressed as a stimulation index.
      Responses were analysed with alanine aminotransferase (ALT) level and
      histological diagnosis. NS3- and core-antigen specific responses in all patient
      groups were significantly higher than in the healthy control group. E1- and
      E2/NS1-antigen-specific responses in the patient group with ALT levels exceeding
      100 IU/L were significantly higher than those in other patient groups.
      Histological diagnosis was not correlated to the intensity of the core- and NS3
      specific responses. E1- and E2/NS1-antigens induced significantly elevated
      responses in patients with chronic active hepatitis and liver cirrhosis compared
      with results in the healthy control group and in patients with chronic persistent
      hepatitis. In conclusion, the significantly elevated responses to core- and NS3
      antigens may be related to HCV infection and such responses to E1- and E2/NS1
      antigens could be related to the severity and activity of the disease.

PMID- 8872765
TI  - Real-time monitoring of HCV-RNA by single tube assay kit and potential importance
      for predicting virological sustained response in patients with chronic hepatitis
      C.
AB  - In an attempt to predict virological sustained responders among patients with
      chronic hepatitis C after interferon therapy, HCV-RNA in serum was measured by a
      one tube RT-PCR assay kit using the RNA corresponding to 5 microL serum (standard
      assay) or 300 microL serum (enhanced-sensitivity assay). Dilution analysis
      revealed that sensitivity of the 'enhanced-sensitivity assay' increased by 10-100
      fold when compared with a 'standard assay'. Using these assays, prospective study
      of interferon therapy on 38 HCV-RNA seropositive cases with chronic hepatitis
      (total amount 702 MU; duration of treatment 5-6 months) was performed. At the end
      of treatment, six were still positive and 32 became negative by the "standard
      assay', whereas an additional eight cases became positive (total 14 cases
      positive; the remaining 24 cases negative) by the 'enhanced-sensitivity assay'.
      Hepatitis C viral RNA state at the end of treatment remained the same 6 months
      later in 23 cases (61%) by a 'standard assay' and in 31 (82%) by the 'enhanced
      sensitivity assay'. Of importance was that all patients (14 cases) demonstrating
      HCV-RNA in serum at the end of therapy, even by the "enhanced-sensitivity assay',
      did not show the disappearance of HCV-RNA in serum despite the long follow up.
      From these results, in order to improve our treatment efficacy, we should try to
      modify our treatment protocol to the extent that at least HCV-RNA becomes
      undetectable. That can be only feasible during treatment by real-time monitoring
      of HCV-RNA.

PMID- 8872766
TI  - Relationship between the intrahepatic expression of interferon-alpha receptor
      mRNA and the histological progress of hepatitis C virus-associated chronic liver
      diseases.
AB  - Histological progress is one of the predictors of an unfavourable response to
      interferon (IFN) therapy in hepatitis C virus (HCV)-associated chronic liver
      diseases (CLD). The aim of the present study was to investigate whether
      histological progress has an association with the expression of IFN receptor (IFN
      Rc) in the liver. Expression of mRNA of the IFN-Rc for IFN-alpha was investigated
      by reverse transcription polymerase chain reaction using liver biopsy specimens
      from 37 HCV-associated CLD comprising 11 liver cirrhosis (LC) and 26 chronic
      hepatitis (CH) cases. IFN-alpha and IFN-beta mRNA were detected in over 90% of
      subjects. In contrast, the detection rate of IFN-Rc mRNA in chronic persistent
      hepatitis, chronic hepatitis 2A, chronic hepatitis 2B and liver cirrhosis (LC)
      was 100, 71.4, 22.2 and 0%, respectively. The absence of IFN-Rc mRNA was
      significantly associated with the severity of fibrosis of the liver. These
      results indicated that IFN-Rc expression decreases with the histological progress
      of the disease, suggesting that lower expression of IFN-Rc mRNA may be partially
      responsible for the poor IFN response in LC.

PMID- 8872767
TI  - Efficacy and side effects of intermittent recombinant interferon-alpha 2a in
      chronic aggressive hepatitis C: with or without initial daily administration.
AB  - To investigate the therapeutic effect and incidence of side effects of
      recombinant interferon-alpha 2a (IFN-alpha) in chronic aggressive hepatitis C
      under stratification by administration mode, a study was conducted by assigning
      patients to either group A (daily consecutive administration of 9 million units
      (MU) IFN-alpha for 2 weeks and, thereafter, 3 MU intermittently 3 times weekly
      for 22 weeks) or group B (exclusively intermittent administration; 9 MU IFN-alpha
      twice weekly or 6 MU IFN-alpha thrice weekly for 24 weeks). The 28 patients in
      group A received IFN-alpha for 24 weeks up to a total dose of 324 MU and the 53
      patients in group B received the same for 24 weeks up to a total dose of 432 MU.
      When recovery was defined as the absence of hepatitis C virus (HCV)-RNA 6 months
      after the completion of treatment, the rate of recovery for group A was 32.1% and
      that for group B was 37.7%, the latter being higher but without significance.
      Side effects in groups A and B consisted of leucopenia occupying 14.3 and 7.5%,
      respectively, and thrombocytopenia occupying 42.9 and 11.3%, respectively; group
      B exhibited lower values for both side effects. No difference was detected
      between these groups in other side effects, including pyrexia, generalized
      malaise, arthralgia or psilosis. Intermittent administration from the outset
      permitted shortened duration of hospitalization and earlier rehabilitation.
      Intermittent administration of INF-alpha is required when treating patients with
      chronic hepatitis C showing lower leucocyte or platelet counts.

PMID- 8872768
TI  - Case report: primary splenic non-Hodgkin's B cell lymphoma in a patient with
      chronic hepatitis C.
AB  - A case of primary splenic lymphoma in a patient with chronic hepatitis C is
      reported. A 69-year-old man with chronic hepatitis C was admitted to Fukuoka City
      Hospital for evaluation of an enlarging splenic tumour. In the spleen,
      ultrasonographic examination revealed a hypoechoic tumour and computed tomography
      demonstrated a non-enhancing low density area measuring 7 cm in diameter; coeliac
      angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of
      the radioisotope in the splenic tumour. A splenectomy was performed and the
      morphological and immunohistochemical findings of this tumour were compatible
      with those of non-Hodgin's B cell lymphoma. Recently, cases of malignant B cell
      lymphoma associated with hepatitis C virus infection have been reported.
      Lymphotropism of hepatitis C virus may play a pathological role in the
      development of non-Hodgkin's lymphoma. We emphasize the importance of considering
      lymphoma in the differential diagnosis of extrahepatic disorders during the
      course of chronic hepatitis C virus infections.

PMID- 8872769
TI  - Frequency and factors influencing portal hypertensive gastropathy and
      duodenopathy in cirrhotic portal hypertension.
AB  - Portal hypertensive gastropathy and duodenopathy are distinct clinical and
      endoscopic entities. Data on factors influencing the development of these lesions
      are still emerging. Data on portal hypertensive duodenopathy are scarce. We
      prospectively studied 230 patients with liver cirrhosis and oesophageal varices
      attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of
      Medical Sciences. One hundred and forty-two patients had no history of upper
      gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic
      appearances were recorded before starting patients on a sclerotherapy programme.
      Forty-four patients were re-evaluated after variceal eradication. The frequency
      of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%,
      respectively. Mild PHG was present in 85% and was severe in the rest. Portal
      hypertensive duodenopathy was mild in 50%, while in the other half it was severe.
      There was no relationship of PHG and PHD to: (i) a history of upper
      gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of
      liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores
      (P = NS for all). The prevalence of PHG was higher in those patients with
      oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal
      varices alone (68 of 123; 55%; P < 0.05). However, no such increase in frequency
      of PHD was noted in patients with oesophagogastric varices. Sclerotherapy
      increased the frequency of PHG. Twenty-four patients had PHG before starting
      sclerotherapy, while it was noted in 33 patients 1-3 months after variceal
      eradication (P < 0.05). In contrast, there was no increase in the prevalence of
      portal hypertensive duodenopathy after sclerotherapy (P = NS). There was no
      correlation between endoscopic and histological changes of PHG and PHD. In
      conclusion, PHG is quite frequent in patients with cirrhosis and its frequency
      increases with the presence of oesophagogastric varices and after sclerotherapy.
      However, the frequency of PHD is low and is not affected by the factors studied.

PMID- 8872770
TI  - Case report: delayed resolution of severe pulmonary hypertension after isolated
      liver transplantation in a patient with cirrhosis.
AB  - Pulmonary hypertension is now recognized to be a rare association of liver
      disease and portal hypertension. This report describes the slow resolution of
      symptomatic pulmonary hypertension in a 33-year-old woman with cirrhosis who
      underwent isolated liver transplantation. The patient survived the surgery and
      perioperative period without significant haemodynamic compromise. After liver
      transplantation, the patient was monitored with regular Doppler echocardiography.
      By 27 months the pulmonary hypertension had almost completely resolved. This
      observation is important, as it suggests that patients with severe pulmonary
      hypertension who survive the perioperative period may have an excellent outcome,
      although resolution may be slow.

PMID- 8872771
TI  - Comparison of haptoglobin and apolipoprotein A-I on biliary lipid particles
      involved in cholesterol crystallization.
AB  - Several proteins are known to modulate cholesterol crystallization. We recently
      demonstrated that haptoglobin has cholesterol crystallization promoting activity.
      However, this effect is still not well understood mechanistically. The current
      study examined the distribution of haptoglobin compared to apolipoprotein A-I
      (apo A-I) to micelles, vesicles and crystals as an initial step in providing a
      focus for further studies of the mechanism of cholesterol crystallization
      activity. Specific protein purification was accomplished by immunoaffinity
      chromatography. The crystallization-promoting activity of biliary haptoglobin,
      albumin and commercial apo A-I was measured by a photometric crystal growth
      assay. The distribution of micelles, vesicles and proteins in model bile was
      determined by Sepharose CL-6B column chromatography. Detection of the presence of
      test proteins in cholesterol crystals was determined using specific 125I
      radiolabelled proteins. Haptoglobin (20 micrograms/mL) showed a significant
      crystallization promoting-activity, whereas apo A-I (30 micrograms/mL) only
      tended to show a slight inhibitory activity. The cholesterol crystal-bound
      protein in each case was found to be less than 1% of the total concentration of
      that protein that had been added to the model bile system. The elution profile of
      commercial apo A-I from a Sepharose CL-6B column was strikingly altered when it
      was added to model bile prior to elution. In contrast, the column elution
      profiles for both haptoglobin and albumin were unchanged when model bile was
      similarly added to the sample. Haptoglobin increased the amount of cholesterol
      found in the vesicular fraction when compared to apo A-I. Haptoglobin does not
      bind tightly to either biliary lipid particles or to cholesterol crystals but
      does increase the amount of cholesterol in vesicles by inducing a shift from
      micellar cholesterol (P = 0.046). This shift appears to explain in part its
      promoting effect on cholesterol crystallization.

PMID- 8872772
TI  - Reduction of intestinal apo A-IV mRNA levels in the cirrhotic rat.
AB  - In the present study, intestinal apo A-IV synthesis was investigated using a
      carbon tetrachloride (CCl4)-induced cirrhosis rat model. Triglyceride (TG)
      content in rat cirrhotic liver was increased markedly by 170% (P < 0.001) and apo
      B was increased by 20% (P < 0.05) compared with control levels. These results
      reflected the steatotic change in the liver. In contrast, TG levels in the small
      intestine of cirrhotic rats decreased significantly (P < 0.01). In addition,
      intestinal apo A-IV (jejunum P < 0.001; ileum P < 0.01) and its mRNA levels
      (jejunum P < 0.01; ileum P < 0.05) were also reduced. The decreased apo A-IV
      content in the jejunum was confirmed by immunohistochemical analysis. These
      results indicate that intestinal apo A-IV synthesis in cirrhosis is suppressed,
      at least under the condition of an overnight fast. Therefore, decreased
      intestinal apo A-IV synthesis may relate to the decreased ability to absorb fat
      in cirrhosis, but a fat-loading study will be necessary to confirm this
      hypothesis. It is unknown from the present study why serum apo A-IV level is not
      significantly decreased, despite a reduction in apo A-IV synthesis. The clearance
      of apo A-IV by the liver may be delayed or apo A-IV synthesis may be rather
      markedly enhanced during fat absorption in liver cirrhosis.

PMID- 8872773
TI  - Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma.
AB  - To assess the characteristics of intrahepatic metastatic lesions (IML) in
      hepatocellular carcinoma (HCC), we analysed both the histological features and
      proliferative activities of 15 resected cases of HCC accompanied by IML. The
      histological features of the IML were essentially the same as those observed in
      the main nodules in 12 (80%) of 15 cases. In 13 (87%) of 15 cases, the labelling
      index of proliferating cell nuclear antigen (PCNA) in the IML was either higher
      than or the same as in the main nodules. In 10 (77%) of 13 cases, the MIB-1
      labelling index in the IML was either higher than or the same as in the main
      nodules. The results indicate that the histological features of the IML are
      essentially the same as those of the main nodules, while the proliferative
      activities in the IML were generally higher than those in the main nodules. Such
      characteristics may thus provide a clue to help distinguish intrahepatic
      metastasis from the multicentric occurrence of HCC.

PMID- 8872774
TI  - A clinicopathological study on combined hepatocellular and cholangiocarcinoma.
AB  - We clinicopathologically studied 23 surgically resected cases of combined
      hepatocellular and cholangiocarcinoma (HCC-CC). The frequency of this cancer in
      our subjects, who had primary liver cancer and who underwent hepatectomy, was
      6.3%. The mean age of patients was 64.0 years old and the male: female ratio was
      1.9:1. Serum alpha-fetoprotein was positive in 70% of cases and its levels were
      relatively low (< or = 1000 ng/mL) in most cases. The positive rate of serum
      carcinoembryonic antigen was 18% and its levels were also low. In regard to
      hepatitis virus markers, 17% of the 20 combined HCC-CC cases were positive to HBs
      antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC-CC
      cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were
      classified macroscopically into a separated type (HCC and CC are clearly
      separated 17%), a HCC-predominant type (resembles HCC 49%), and a CC-predominant
      type (resembles CC 34%). The separated and HCC-predominant types were associated
      with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver
      cirrhosis presented the features of HCC more apparently, while those without
      liver cirrhosis presented the features of CC. Histologically, all cases were
      classified into either Type I (HCC and CC were clearly distinguished; 17%), Type
      II (HCC and CC were contiguous and shared transitional features; 66%), and Type
      III (cancer cells were able to be evaluated as either HCC or CC and were
      considered to be an intermediate type; 17%). Immunohistological stains for
      cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive
      to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost
      indistinguishable, such as Type III), indicates the presence of intermediate
      tumour cells that can differentiate either to HCC or CC.

PMID- 8872775
TI  - Case report: gastrointestinal bleeding from a hepatocellular carcinoma invading
      the transverse colon.
AB  - A 72-year-old woman with cirrhosis of the liver was treated repeatedly by
      transcatheter arterial embolization for multifocal hepatocellular carcinomas. She
      developed gastrointestinal bleeding secondary to direct invasion of the wall of
      the transverse colon. The diagnosis was made pre-operatively by colonoscopy and
      the patient was treated successfully. This rare complication of hepatocellular
      carcinoma was due to the protrusive type of growth exhibited by this tumour and
      may have been affected by the transcatheter arterial embolization.

PMID- 8872776
TI  - Case report: mucin-producing cystic neoplasm of the pancreas with onset in
      childhood.
AB  - Mucin-producing tumours of the pancreas have been recently reported with
      increasing frequency and most cases have occurred in middle-aged and elderly
      people. In the present report, a case of a 21-year-old man with mucinous
      cystadenoma of the pancreas is reported. He had a long history of recurrent
      pancreatitis from the age of 8. When he was aged 10, the first branch of the main
      pancreatic duct was shown to be enlarged on endoscopic retrograde
      pancreaticography (ERP). A series of ERP studies and computed tomography scans
      performed over a period of 11 years demonstrated continuing growth of this
      enlargement of the pancreatic duct. Pancreaticoduodenectomy was performed and the
      patient has been well without further episodes of acute pancreatitis and has been
      free of recurrent tumour for 1 year.

PMID- 8872777
TI  - Case report: intrahepatic cholangiocarcinoma with rhabdoid transformation.
AB  - Sarcomatous transformation is found in approximately 5% of patients with
      intrahepatic cholangiocarcinoma. According to previous reports, sarcomatous
      cholangiocarcinomas are composed of spindle-shaped cells and/or multinucleated
      giant cells. Usually, vimentin is expressed by these sarcomatoid cells. We report
      a case of intrahepatic cholangiocarcinoma with an element of rhabdoid cells that
      occurred in a 61-year-old woman admitted for back pain. Various imaging
      techniques demonstrated multiple liver masses. Histologically, these tumours
      formed in both sarcomatous and ordinary tubular adenocarcinomatous areas. The
      sarcomatoid areas were occupied mainly by loosely arranged, eosinophilic rhabdoid
      cells, which expressed both keratin and vimentin. These findings suggest that
      rhabdoid cells may occur in an undifferentiated stage of cholangiocarcinoma and
      possess a strong tendency to metastasize.

PMID- 8872778
TI  - Abnormal gastro-oesophageal reflux in Chinese with atypical chest pain.
AB  - Although atypical chest pain has been well described in the Western population,
      its frequency in Chinese is unknown. Over a period of 42 months, we studied 521
      Chinese patients with chest pain and identified 108 patients (20.7%) whose pain
      was not related to cardiac causes, as determined by exercise ECG or cardiac
      catheterization. Using 24 h ambulatory pH monitoring and baseline oesophageal
      manometry, 28.7, 19.4 and 5.6% of these patients were found to have abnormal
      reflux parameters, abnormal manometric findings or both, respectively. There were
      significantly more patients complaining of chest pain during the study in the
      gastro-oesophageal reflux disease (GERD) group than in the non-GERD group (16/31
      vs 20/77; P < 0.001). The lower oesophageal sphincter pressure was lower in those
      with abnormal reflex parameters than in those with normal reflux parameters (12.7
      +/- 5.4 vs 17.8 +/- 5.8 mmHg; P < 0.05). There was no significant difference in
      symptoms, such as heartburn (54.8 vs 42.9%), regurgitation (38.7 vs 35.1%) and
      dysphagia (19.4 vs 24.7%), among the two groups. Non-specific changes were the
      most frequent baseline motility pattern. In conclusion, atypical chest pain and
      gastro-oesophageal reflux disease are not uncommon in Chinese and this deserves
      special emphasis as the continuation of anti-anginal drugs may aggravate their
      condition.

PMID- 8872779
TI  - Effects of endoscopic variceal sclerotherapy on azygos vein blood flow and
      systemic haemodynamics.
AB  - The present study was designed to determine the systemic haemodynamic effects of
      obliterating oesophageal varices by endoscopic sclerotherapy. We evaluated
      systemic and splanchnic haemodynamics before and after the first course of
      sclerotherapy in cirrhotic patients. The baseline cardiac index was significantly
      correlated with baseline azygos vein blood flow (r = 0.64; P < 0.01) and the
      azygos vein blood flow and cardiac index significantly decreased (-33% and -16%,
      respectively; P < 0.01) following sclerotherapy. The systemic vascular resistance
      index was also increased significantly (+ 20%; P < 0.01) in these patients.
      Moreover, the per cent change in azygos vein blood flow was directly correlated
      with that of the cardiac index (r = 0.51; P < 0.03). We conclude from these
      findings that the obliteration of portosystemic collaterals by sclerotherapy
      significantly reverses hyperdynamic circulation in such patients via a decrease
      in cardiac preload. The blood flow of the portosystemic shunt per se is a leading
      contributor to the hyperdynamic circulation observed in patients with well
      developed portal systemic collateral vessels.

PMID- 8872780
TI  - Case report: lymphangioma of the oesophagus endoscopically resected.
AB  - Lymphangioma of the oesophagus is an extremely rare entity, with only nine cases
      having been reported worldwide. We report on a 52-year-old woman with oesophageal
      lymphangioma, diagnosed using endoscopic ultrasonography and endoscopically
      resected. No case of malignant transformation of the lymphangioma has been
      reported in the literature. Endoscopic resection seems to be a minimally invasive
      method that is appropriate both for the removal of the tumour and precise
      diagnosis.

PMID- 8872781
TI  - Suicidal ideation in primary care.
AB  - OBJECTIVE: To describe the prevalence and clinical characteristics of primary
      care patients who report suicidal ideation during the month before their medical
      visit. DESIGN: Analysis of a self-administered suicidal ideation screening item
      using sociodemographic data, treatment history, and clinical data from structured
      interviews. SETTING: Three Rhode Island private family practices, a South
      Carolina family medicine residency, and a California prepaid internal medicine
      group practice. PATIENTS: Adult primary care patients (N = 2,749), 18 to 70 years
      old, who are able to read and write English, able to complete study forms, and
      willing to provide informed consent. RESULTS: Sixty-seven (2.44%) of the patients
      reported suicidal ideation ("feeling suicidal") during the past month, and most
      of those patients (58.2%) received no mental health care during that time. The
      adjusted risk of suicidal ideation was significantly elevated for patients with
      self-reported fair or poor physical health (odds ratio [OR] 2.5; 95% confidence
      interval [CI] 1.5, 4.1), fair to poor emotional health (OR 18.0; 95% CI 8.8,
      37.0), marital distress (OR 4.4; 95% CI 2.2, 8.8), and recent mental health
      related work loss (OR 6.3; 95% CI 3.7, 10.5). In the California sample, patients
      with major depression (R 31.2; 95% CI 12.8, 76.1). generalized anxiety disorder
      (OR 23.4; 95% CI 8.1, 67.1), and drug abuse or dependence (OR 9.6; 95% CI 2.9,
      31.6) were at increased risk of suicidal ideation. The "feeling suicidal" item
      identified 10 of 12 patients who acknowledged a recent plan to kill themselves.
      CONCLUSIONS: In these primary care patients, suicidal ideation is strongly
      associated with mental disorder and mental health-related functional impairment,
      and can be detected with a single self-report "feeling suicidal" item.

PMID- 8872782
TI  - Use of morning report to enhance adverse event detection.
AB  - OBJECTIVE: To determine whether or not prompting of medical residents at morning
      report enhances reporting of adverse events in hospitalized patients. DESIGN:
      Prospective trial comparing 3-month blocks of intensive prompting, modest
      prompting, and no prompting on adverse event reporting by housestaff at morning
      report. SETTING: Inpatient internal medicine service at a university-affiliated,
      Veterans Affairs Medical Center teaching hospital. INTERVENTIONS: Intensive
      prompting (daily), modest prompting (once or twice weekly), and no prompting of
      medical residents to report hospital-associated adverse events. MEASUREMENTS AND
      MAIN RESULTS: The number, type, and severity of hospital-acquired adverse events
      occurring on an internal medicine service were determined during the various
      periods of intervention on a per houseofficer basis. Residents were reminded to
      record events once or twice weekly, daily, or not at all. These data were
      compared with those identified by usual hospital surveillance. The addition of
      housestaff reporting to usual hospital surveillance increased the numbers of
      adverse events reported. There was little overlap in episodes reported by the two
      strategies. Increasing the level of prompting increased the number of reports per
      houseofficer. Housestaff prompting increased reporting at all levels of adverse
      event severity from mild to serious and detected a wide variety of types of
      adverse events, especially adverse drug reactions and procedure complications.
      CONCLUSIONS: Our study demonstrates that physician self-reporting of adverse
      events adds to the usual hospital surveillance adverse event reporting, and finds
      that such reporting can be easily accomplished within the context of a daily
      teaching activity. The information provided about adverse events by housestaff at
      morning report is additive to that obtained by usual surveillance methods. The
      use of such a strategy provides information in a timely fashion.

PMID- 8872783
TI  - Excess costs from gastrointestinal disease associated with nonsteroidal anti
      inflammatory drugs.
AB  - OBJECTIVE: To quantify medical care costs for the diagnosis and treatment of
      gastrointestinal disorders attributable to use of nonsteroidal anti-inflammatory
      drugs (NSAIDs) other than aspirin in elderly persons. DESIGN AND SETTING:
      Retrospective cohort study of 75,350 Tennessee Medicaid enrollees at least 65
      years of age. MEASUREMENTS: The cohort was classified by baseline NSAID use as
      nonusers (no use preceding 1988), occasional users (< 75% of days) or regular
      users (> or = 75% of days). For the follow-up year (1989), we calculated annual
      rates of utilization of and Medicare/Medicaid payments for: medical care for
      NSAID-associated gastrointestinal disorders; hospitalizations/emergency
      department visits for peptic ulcers, gastritis/duodenitis, and gastrointestinal
      bleeding; outpatient upper and lower gastrointestinal tract radiologic and
      endoscopic examinations; and histamine2 (H2)-receptor antagonist, sucralfate, and
      antacid prescriptions. Rates were adjusted for demographic characteristics and
      baseline health care utilization. RESULTS: Among nonusers of NSAIDs, the adjusted
      mean annual payment for all types of medical care for study gastrointestinal
      disorders was $134. This increased to $180 among occasional users, an excess of
      $46 (p < .001); and to $244 among regular users, an excess of $111 (p < .001,
      comparison with both nonusers and occasional users). Cohort members with any
      baseline year NSAID use had an adjusted mean annual payment of $191, $57 (p <
      .001) higher than that for nonusers. In both users and nonusers of NSAIDs,
      medications and inpatient care accounted for the largest component of costs.
      Among regular NSAID users, excess payments increased with baseline NSAID dose:
      $56, $120, and $157 for less than 1, 1 to 2, and more than 2 standard units per
      day, respectively (p < .01, linear trend). CONCLUSIONS: Nonsteroidal anti
      inflammatory drug (NSAID) use in elderly patients was associated with substantial
      excess costs and utilization of medical care for gastrointestinal disorders.

PMID- 8872784
TI  - Meeting walk-in patients' expectations for testing. Effects on satisfaction.
AB  - OBJECTIVE: To examine the relation between meeting expectations for tests and
      visit satisfaction in walk-in patients. DESIGN: Survey of patients before and
      after the visit. SETTING: Walk-in medical clinic at a Veterans Affairs Medical
      Center. PATIENTS: 143 male veterans were eligible for this study: 128 agreed to
      participate; 109 completed both questionnaires. MEASUREMENTS: Before the visit,
      we measured health status, baseline satisfaction with care, and expectations for
      common tests. After the visit, we measured visit-specific satisfaction, patient
      perception of provider interpersonal behavior (provider humanism), and patient
      report of whether specific tests were received. Logistic regression was used to
      determine the effect of meeting expectations for tests while controlling for
      other factors. RESULTS: Of all patients, 62% expected one or more tests, nearly
      as many as expected a medication or a diagnosis. In multivariate analysis
      restricted to those expecting tests, provider humanism was the sole significant
      predictor of visit-specific satisfaction (odds ration [OR] 6.4; 95% confidence
      interval [CI] 1.6, 26.1). The proportion of expectations for testing that were
      met was not significantly associated with satisfaction (OR 1.05; 95% CI 0.92,
      1.21). CONCLUSIONS: Meeting patient expectations for tests does not have an
      important effect on satisfaction. Even in the walk-in setting, patient perception
      of the providers' interpersonal behavior was a more important factor in
      satisfaction with the visit. Physicians who order tests solely to improve patient
      satisfaction may be able to reduce unnecessary testing without decreasing patient
      satisfaction.

PMID- 8872785
TI  - Improving residents' teaching skills and attitudes toward teaching.
AB  - OBJECTIVE: To determine whether a short, 3-hour teaching skills workshop could
      improve residents' teaching performances and attitudes toward teaching. DESIGN:
      Controlled study. PARTICIPANTS AND SETTING: Forty-four second- and third-year
      residents in a university-based internal medicine residency program.
      INTERVENTIONS: Twenty-two residents were assigned to a nonparticipant (control)
      group, and 22 residents were assigned to a 3-hour teaching skills workshop
      designed to help them establish a positive learning climate and provide effective
      feedback to medical students. MEASUREMENTS: Questionnaires completed by medical
      students and residents that measured the residents' abilities to establish a
      positive learning climate and provide feedback, their overall teaching skills,
      and their attitudes toward teaching. RESULTS: Four months after the workshop
      intervention, workshop participants improved their learning climate and feedback
      according to student evaluations (p = .02, p = .001, respectively) and resident
      self-assessments (p = .002, p = .01, respectively) compared with nonparticipants.
      Overall teaching skills were not significantly changed (p = .20 for student
      evaluation and p = .09 for self-assessments). Workshop participants also gained
      more confidence in their teaching (p = .001), and adopted more learner-centered
      approaches to teaching than did nonparticipants. CONCLUSIONS: A 3-hour
      instructional workshop is a feasible and effective method to help residents
      improve their teaching skills, their confidence in teaching, and the approaches
      they use to teach medical students on the wards.

PMID- 8872786
TI  - Strategies for managing uncertainty and complexity.
AB  - OBJECTIVES: To identify strategies involved in the diagnosis and treatment plans
      of primary care problems that are uncertain and complex. METHODS: In this
      exploratory study we observed primary care physicians encountering standardized
      patients who portrayed typical primary care problems involving uncertainty and
      complexity. First, we analyzed 10 tapes of nine physicians with a range of
      clinical experience (first-year residents through faculty physicians) interacting
      with four standardized patient cases (headache, back pain, hypertension, and
      abdominal pain). We analyzed the 10 tapes to determine the regular occurrence of
      physician behavior patterns that we later described as strategies. Then, using a
      written questionnaire, 19 general internal medicine faculty physicians from our
      hospital and from an affiliated hospital rated the perceived importance of these
      strategies for clinical practice in general. Finally, we checked the incidence of
      the strategies: (1) across a range of six cases (headache, back pain,
      hypertension, abdominal pain, fatigue, and well-adult care) using six first-year
      residents (a total of 19 encounters), and (2) across different levels of clinical
      experience using the standardized patient case of headache involving eight
      physicians (first-year residents through faculty physicians). RESULTS: Nine
      strategies were identified, and each was rated as important to primary care
      clinical practice. The strategies were: (1) defines the context of the diagnosis
      and explains the signs and symptoms as part of the expected spectrum of the
      disease; (2) eliminates alternative diagnoses by dealing with patient fears,
      giving reasons in the context of the patient's belief system; (3) describes the
      prognosis in terms of the likely course of the disease and expectations of
      treatment; (4) negotiates key problems or issues that are important to both
      patient and physician; (5) negotiates the plan and ensures patient understands,
      and is willing and able to comply, given his/her particular context; (6) keeps
      diagnostic options open by making provisional diagnoses while keeping
      alternatives in mind; (7) is circumspect and takes action to minimize the
      possibility of missing other critical diagnoses; (8) plays for time by allowing
      signs and symptoms to develop to help clarify the diagnosis; and (9) plans for
      contingencies by providing appropriate if/then statements concerning situations
      requiring further action. The strategies were used in each of the six cases, and
      by physicians with all levels of clinical experience. CONCLUSIONS: The nine
      strategies led to the generation of a construct we termed "strategic medical
      management," which refers to the management (diagnosis and proposed treatment) of
      uncertain and complex medical problems in primary care. The construct provides a
      more elaborated framework in which to view clinical decision making and
      integrates recent ideas concerning doctor-patient communication into this
      process. Strategic medical management appears to be based on tacit knowledge that
      is seldom explicity articulated or taught. It has potential implications for
      enhancing instruction and assessment in medical education.

PMID- 8872787
TI  - Principles of practice concerning the Jewish patient.

PMID- 8872788
TI  - Physical diagnosis in the 1990s. Art or artifact?

PMID- 8872789
TI  - Telling patients about the diagnosis of HIV infection.
AB  - This study used a questionnaire to examine how patients in the HIV/AIDS Clinic at
      a Department of Veterans Affairs hospital were told of their diagnosis, by whom,
      and to what degree they were given emotional and educational support. Nearly 17%
      of patients were informed by someone not in the health professions (often
      military personnel), and 27% of patients were notified in a nonprivate setting.
      Forty-seven percent indicated they received little or no educational support at
      the time of diagnosis, while 39% received little or no emotional support.
      Educational and emotional support for patients at the time of HIV diagnosis may
      be lacking.

PMID- 8872790
TI  - Physicians' reasons for failing to comply with computerized preventive care
      guidelines.
AB  - The objective of this study was to assess reasons for physicians' noncompliance
      with computer-generated preventive care reminders. In an academic general
      internal medicine practice, a survey of physicians' reasons for noncompliance
      found that 55% of reminders were not complied with. Reasons included "not
      applicable" in 22.6% (test done elsewhere, patient too ill, no uterus), "next
      visit" in 22.5% (physician too busy, patient too ill), and "patient refuses" in
      9.9% (test not necessary or too costly, patient too busy or fears result). We
      conclude that although noncompliance with reminders is sometimes appropriate,
      making time for prevention and patient education may augment preventive care.

PMID- 8872791
TI  - Comorbidity and length of stay: statistically significant?

PMID- 8872792
TI  - What are internists looking for?

PMID- 8872793
TI  - Communication with non-English-speaking persons.

PMID- 8872794
TI  - Gender differences in hypertension.
AB  - The evidence we have for the US, Australia and Korea indicates that men have
      slightly higher pressures than women and slightly greater prevalence of
      hypertension. In the US this sex difference is reversed at about age 70 and
      persists throughout the rest of the lifespan. How much these gender differences
      affect gender differences in cardiovascular disease manifestations is not clear,
      but remains an intriguing possibility.

PMID- 8872795
TI  - Assessment of drug efficacy using home self-blood pressure measurement: the SMART
      study. Self Measurement for the Assessment of the Response to Trandolapril.
AB  - The SMART study (Self Measurement for the Assessment of the Response to
      Trandolapril) was a large scale trial conducted by general practitioners in order
      to assess the informative value of home self-measured blood pressure (BP) for the
      evaluation of therapeutic intervention. After a 2-week wash-out period, patients
      with office diastolic blood pressure (DBP) between 95 and 120 mm Hg received
      trandolapril, 2 mg once daily for 4 weeks. Four days of self-recorded BP were
      performed both at the end of the wash-out period and at the end of the treatment
      period with an automatic printerequipped device using the oscillometric method
      (A&D UA 751). Every day, a series of three consecutive measurements was planned
      in the morning before drug intake and repeated in the evening. A total of 1710
      patients (946 men, 764 women) aged 56 +/- 11 entered the study. In the 816
      patients who correctly performed self-measured blood pressure (SMBP) during both
      periods and followed the protocol schedule, office BP (SBP/DBP) decreased from
      166.4 +/- 15/101.4 +/- 6 mm Hg to 144.7 +/- 14/86.1 +/- 8 mm Hg while SMBP
      decreased from 153 +/- 18/94 +/- 10 mm Hg to 139 +/- 16/85 +/- 10 mm Hg. A weak
      correlation was found between the two methods with regard to systolic (r = 0.47,
      P < 0.0001) and diastolic (r = 0.36, P < 0.0001) BP lowering. Individual response
      to therapy varied between the two methods: 633 patients (77.6%) exhibited at
      least a 10 mm Hg office DBP decrease while 493 (60.4%) presented at least a 6 mm
      Hg self measured DBP decrease in the evening; 65% of patients were considered as
      responders with both methods. The 24-h therapeutic coverage was assessed by the
      morning to evening BP decrease ratio (M/E ratio) which represents the ratio of
      the trough effect to the 12-h post dosing efficacy. Both population and
      individual M/E ratios ranged between 73% and 86% thus confirming the long
      duration of action of trandolapril. IN CONCLUSION: (1) discrepancies between
      office and self-measured BP evaluation of therapeutic response have been pointed
      out: agreement between the two methods is obtained in only 65% of patients,
      mainly due to intra-individual BP variability and recording conditions; and (2)
      self-measured BP could be a potential tool to explore the 24-h therapeutic
      coverage.

PMID- 8872796
TI  - Are four duplicate remeasurements sufficient for diagnosing mild hypertension?
AB  - The aim of this study was to investigate if four duplicate blood pressure (BP)
      remeasurements are sufficient for diagnosing hypertension in potentially
      hypertensive subjects. The subjects were 99 outpatients who were included on the
      basis of elevated diastolic (95 < or = DBP < or = 115 mm Hg) or systolic (160 <
      or = SBP < or = 200 mm Hg) BP. After inclusion all patients underwent nine
      subsequent duplicate BP measurements over a period of 7 months. None of the
      patients received hypotensive drug treatment during the study. Between the first
      (initial) and second measurements there were significant reductions in systolic
      (161.0-152.5 mm Hg) and diastolic (101.5-97.1 mm Hg) BPs (P < 0.01). Differences
      between the subsequent measurements were not statistically significant. A linear
      regression analysis proved that the "conceptual average BP' (the average of the
      last five visits) which was chosen as the reference value was stable. The decline
      of standard deviations of differences between two, three and four duplicate
      remeasurements on one hand, and the reference value on the other was found to be
      strikingly small. After four duplicate remeasurements, there was
      misclassification in 56% (systolic) and 38% (diastolic). We conclude that the
      numbers of two, three or four BP measurements recommended by international
      guidelines for diagnosing hypertension are too low. Even after four duplicate
      remeasurements a considerable amount of misclassification remains.

PMID- 8872797
TI  - Essential and secondary hypertension and sleep-disordered breathing: a unifying
      hypothesis.
AB  - Obstructive sleep apnea (OSA) is a disorder in which there is repetitive collapse
      and closing of the pharynx during sleep. There is growing evidence to suggest
      that this disorder is a major cause of essential hypertension (EH) and that
      successful treatment of OSA can reduce the blood pressure (BP) significantly. In
      addition many other patients with EH have milder forms of sleep related breathing
      disorders (SRBD) like snoring, and upper airway resistance syndrome (UARS) which,
      while not as severe as OSA, may be severe enough to also cause systemic
      hypertension. We therefore propose a unifying hypothesis-that many patients with
      EH may have sleep related breathing disturbances (SRBD) and treatment of these
      disorders may improve the BP. SRBD could also explain many of the
      epidemiological, clinical, hereditary, biochemical, hematological and
      physiological characteristics seen in EH. In addition, many types of secondary
      hypertension (those caused by excessive alcohol intake, chronic renal failure,
      diabetes, hypothyroidism or acromegaly) have a higher than normal prevalence of
      OSA and OSA may contribute to the hypertension and organ damage found in these
      conditions as well. Thus SRBD may play an important role in the production of
      many cases of essential and secondary hypertension, and their early detection and
      treatment could reduce the hypertension and organ damage seen in these
      conditions.

PMID- 8872798
TI  - Body composition and blood pressure: which indices of fatness show the strongest
      correlation?
AB  - We studied the strength of association of different indices of body composition
      with blood pressure (BP) in 430 healthy persons (222 males, 208 females) living
      in southern Saudi Arabia. The percentage of fat, fat mass (FM), fat mass index
      (FMI) and body mass index (BMI), but not the fat free mass (FFM) were greater in
      women than in men. All these indices were significantly correlated with BP except
      height and triceps fold thickness. However, the highest correlation with BP
      existed with the body weight, followed by FFM and BMI and the lowest correlation
      existed with FM and fat free index (FFI). Thus, this study showed that weight
      related body composition indices are better correlated with BP than height
      related ones. This may be of importance when addressing BP relation with the
      degree of fatness.

PMID- 8872799
TI  - Hypotensive reactions on passive head-up tilt testing of hypertensive patients.
AB  - With the aid of a protracted passive postural test, the rate of occurrence and
      the variants of orthostatic hypotensive reactions in hypertensive patients were
      studied. Three hundred and eighty-two consecutive tilt tests in 161 hypertensive
      patients, 89.4% of whom were taking antihypertensive medications, were reviewed.
      Orthostatic hypotensive reactions were recognized in 33.8% of examinations.
      Thirty-one hypotensive episodes (8.1%) were associated with symptoms of cerebral
      ischemia, resulting in termination of the tilt test at a median of 5 min from
      onset (range 1-30 min). A survey of possible risk markers of symptomatic
      hypotensive reactions during tilt showed that increasing age was associated with
      significantly increased risk (P < 0.001), while gender, office blood pressure
      (BP), diabetes mellitus, ischemic heart disease, anxiety, history of syncope, and
      treatment with antihypertensive drugs were not. Asymptomatic orthostatic
      hypotension early in the course of the tilt test was a weak predictor of
      symptomatic hypotensive reactions later during the test (positive predictive
      value 17.4-33.3%). Among the 31 symptomatic hypotensive reactions, 10 were
      typical cases of orthostatic hypotension, four were typical vasovagal reactions,
      and 17 episodes were difficult to classify. The implications of symptomatic
      hypotensive reactions triggered by protracted head-up tilt in hypertensive
      patients are unknown and can only be elucidated in longitudinal studies.

PMID- 8872800
TI  - Control of the human cardiovascular system by nitric oxide.

PMID- 8872801
TI  - Endothelin and blood pressure regulation.

PMID- 8872802
TI  - The role of isoprenoids in vascular smooth muscle: potential benefits of statins
      unrelated to cholesterol lowering.
AB  - Elevated plasma cholesterol is a well recognised risk factor for cardiovascular
      disease. Numerous studies have shown that a reduction in circulating cholesterol
      results in a reduced cardiovascular risk. The statins are a group of cholesterol
      lowering agents which act by inhibition of a key enzyme in cholesterol synthesis;
      3-hydroxy 3-methyliglutaryl coenzyme A (HMG CoA) reductase. This enzyme is
      responsible for the conversion of HMG CoA to mevalonate. In addition to their
      efficacy as cholesterol lowering agents, statins inhibit the proliferation,
      migration and signalling of vascular smooth muscle cells. Inhibition of
      isoprenoid synthesis and resultant reduction in prenylation of key cellular
      proteins such members of p21ras and p21rho families may underlie some of these
      effects.

PMID- 8872803
TI  - Maternal vascular function in pregnancy.

PMID- 8872804
TI  - Hypertension in transplant recipients.

PMID- 8872805
TI  - Gender and cardiovascular risk.

PMID- 8872806
TI  - The prevalence of pseudohypertension in the elderly.
AB  - Pseudohypertension (PHT) could lead to the initiation of unnecessary
      antihypertensive treatment and potentially adverse consequences. The Finapres is
      reported to be a reliable alternative to intra-arterial blood pressure (BP)
      measurements and is unlikely to be distorted by arterial calcification, suggested
      to be a cause of PHT. Finapres measurements were compared with sphygmomanometric
      measures of brachial BP. PHT was defined as a systolic pressure (brachial) > or =
      190 mm Hg and finger systolic < 160 mm Hg or a diastolic pressure (brachial) > or
      = 100 mm Hg and finger pressure < 90 mm Hg. One hundred and twenty-five elderly
      in-patients and out-patients, both hypertensive and normotensive, had a 2.5%
      prevalence of PHT (1 had diastolic PHT in the left arm, 1 had systolic PHT in the
      right arm and 1 had systolic PHT in both arms). A group without PHT, but with
      higher systolic readings with the sphygmomanometer compared with the Finapres (>
      or = 30 mm Hg) was identified. It was thought that the same factors may affect
      both pseudohypertensive and non-pseudohypertensive subjects with such large
      differences. Our data suggest that age plays a role in the presence of higher
      brachial pressures.

PMID- 8872807
TI  - Left ventricular mass and diurnal variation in blood pressure with time after
      cardiac transplant.

PMID- 8872808
TI  - Effects of changes in dietary sodium intake on plasma brain natriuretic peptide
      levels in patients with autosomal dominant polycystic kidney disease.

PMID- 8872809
TI  - Arteriolar length-diameter (L:D) ratio: a geometric parameter of the retinal
      vasculature diagnostic of hypertension.

PMID- 8872810
TI  - Determinants of membrane microviscosity in human erythrocytes: association with
      gender, blood pressure and serum lipids.

PMID- 8872811
TI  - Adrenomedullin acts via stimulation of cyclic AMP and not via calcium signalling
      in vascular cells in culture.

PMID- 8872812
TI  - Effect of captopril on intracellular free calcium ([Ca2+]i) of thymocytes in
      spontaneously hypertensive rats.
AB  - Hypertension is associated with dysfunction of the immune system. Intracellular
      free calcium ([Ca2+]i) was reportedly increased in immune cells, such as
      lymphocytes and thymocytes, both in hypertensive patients and in animals. To
      evaluate if captopril has an effect on the immune system, [Ca2+]i in thymocytes
      was monitored during the development of hypertension from 4-24 weeks, and after
      treatment with captopril for 4 and 12 weeks in spontaneously hypertensive rats
      (SHR). SHR (n = 24) were treated with captopril at a dose of 20 mg/kg/day at 12
      weeks of age after establishment of hypertension. Untreated SHR (n = 17) and
      normotensive Wistar Kyoto (WKY n = 14) served as control. [Ca2+]i of thymocytes
      was measured using Fura-2. It was found that [Ca2+]i of thymocytes decreased both
      in SHR and WKY from 4-12 weeks of age. From 12-24 weeks, [Ca2+]i in thymocytes
      remained at a constant level in WKY. However, [Ca2+]i in thymocytes increased
      significantly in SHR after 12 weeks. Captopril (CAP) treatment significantly
      lowered [Ca2+]i in thymocytes derived from SHR at 24 weeks. This treatment was
      associated with a moderate reduction in systolic blood pressure. Established
      hypertension in SHR is associated with increased [Ca2+]i in thymocytes. This may
      be indicative of immunological dysfunction. Captopril inhibits the increase in
      [Ca2+]i of thymocytes in SHR.

PMID- 8872813
TI  - Angiotensin-converting enzyme (ACE) gene polymorphism and the erythrocyte sodium
      lithium countertransporter (SLC) phenotype in hypertension.
AB  - It has been suggested that the association between altered behaviour of the
      erythrocyte sodium-lithium countertransporter (SLC) and hypertension could be
      secondary to its association with the risk of vascular disease rather than raised
      blood pressure (BP) per se. Homozygosity for the angiotensin-converting enzyme
      (ACE) deletion allele has also been linked to a more severe phenotype for
      cardiovascular disease. The present study investigated whether there is an
      association between these two indicators of vascular risk in patients with
      hypertension. The kinetic characteristics of the countertransporter (SLC
      activity, Vmax and KNa) of patients having the ID ACE-genotype (n = 16) were
      compared with those patients who had the DD genotype (n = 12). The median (range)
      SLC activity (mmol Li/l Red Blood Cells.h) in the ID (0.221 [0.061-0.422]) and DD
      (0.173 [0.094-0.408]) groups were similar (P = 0.28; Mann-Whitney). No
      significant differences in Vmax (mmol Li/l RBC.h) emerged between the two study
      groups (0.279 + 0.124 [ID] vs 0.244 + 0.123 [DD]; P = 0.46; unpaired Student's t
      test); similarly, no differences emerged between the two groups with respect to
      KNa (median [range]; ID, 39.8 [12.4-84.4] vs DD, 35.9 [14.6-78.3]; P = 0.47).
      These data suggest that the SLC phenotype and the ACE-D allele dose are risk
      factors for cardiovascular disease that function independently of one another.

PMID- 8872814
TI  - Stability of atrial natriuretic peptide during storage at -20 degrees C.

PMID- 8872815
TI  - Factor V Leiden polymorphism (FV Q506) in patients with ischaemic heart disease,
      and in different populations groups.
AB  - A point mutation in the factor V gene (FV Q506) renders factor V resistant to
      inactivation by activated protein C. The frequency of this mutation is known to
      be significantly increased in patients with thrombophilia. There are conflicting
      reports on the significance of the polymorphism in patients with ischaemic heart
      disease. We determined the frequency of FV Q506 in a control Caucasian
      population, and compared it with 192 Caucasian patients admitted to coronary care
      and assessed as having myocardial infarction (MI) or unstable angina plus
      previous MI. There was no significant difference between the two groups. A cohort
      of 105 asymptomatic Afro-Caribbeans showed a much reduced frequency of the
      polymorphism.

PMID- 8872816
TI  - Assessing the quality and effects of hypertension control in populations.
AB  - The objectives of hypertension control include early detection, treatment and
      prevention of blood pressure (BP) elevations. In clinical situations, continuous
      evaluation of an Individual's treatment is an inherent part of normal follow-up.
      On the level of populations, however, evaluation of hypertension control calls
      for specially designed action. Evaluation is needed for several reasons; these
      are, inter alia, strategic (to improve the method); economic (to upgrade cost
      effectiveness); and ethical reasons (to morally justify public action). Since
      hypertension control in populations is itself a complex process, its evaluation
      requires, multidimensional approaches. The methodologic experience from three WHO
      studies of this kind has been reported. These were done in different contexts:
      (1) evaluation of the effects of a special multicentre programme for hypertension
      control in populations; (2) long-term monitoring of cardiovascular disease
      incidence; and (3) a project for the assessment of levels and quality of
      hypertension control that is taking place spontaneously. In the first study,
      changes with time were compared in pairs of similar communities, of which one had
      been exposed to an organized programme for the control of hypertension
      ('intervention' vs 'reference' community). The second study uses an elaborate
      system of disease registers and surveys periodically a number of general
      populations. In the third study the actual level and quality of hypertension
      control was analysed in different, mostly European, populations; the findings
      related to the treatment of hypertension were compared with the standards
      suggested by WHO and ISH; other findings were assessed on the basis of common
      sense.

PMID- 8872817
TI  - Planning for a community-based hypertension control program in the inner city.
AB  - Uncontrolled hypertension is a significant problem among African-Americans
      residing in inner city environments. To help address the problem, we are
      developing community-based hypertension control programs in African-American
      communities located in Milwaukee, Wisconsin and Chicago, Illinois. The Milwaukee
      program focuses on an entire, diverse inner city area, while the Chicago program
      is targeted to several more homogeneous African-American neighborhoods. The
      investigators hypothesize that the success of a hypertension control program will
      depend on carefully tailoring the educational approaches to the specific
      characteristics of the target area. Therefore, the study areas that have been
      selected differ with regard to community size and diversity, community
      'stressors' (poverty, unemployment, crime, etc), and types of organizations which
      are present in the community. This paper describes the background and the
      rationale for community hypertension control programs in the inner city. The
      initial approaches to establishing the program by developing interfaces with the
      community and the gathering of baseline data through household surveys are
      described.

PMID- 8872818
TI  - Reassessment of the interaction between a worksite hypertension program and
      private physicians.
AB  - We investigated how nurse practitioners attending at worksite hypertension
      clinics were perceived as care providers by both patients enrolled in the clinics
      and their private physicians. This study indicates a very favorable attitude
      towards nurse practitioners from both patients and private practitioners and
      gives additional support for the utilization of nurse practitioners as effective
      health care providers in the management of common and chronic illness.

PMID- 8872819
TI  - Hypertension control in multi-ethnic primary care clinics.
AB  - The most recent JNC-V guidelines for hypertension treatment call for control of
      blood pressure (BP) to < 140/90 mm Hg, with increased emphasis on control of
      systolic pressure. To determine the extent and determinants of BP control in a
      large multi-ethnic, low-income clinic population of diagnosed hypertensives
      immediately prior to issuance of the new guidelines, we reviewed the medical
      records of 2925 patients sampled from a population of over 14,000 hypertensives
      following in a network of nine primary care clinics operated by the Harris County
      Hospital District in Houston, Texas. Variables extracted from the medical record
      included: systolic (SBP) and diastolic (DBP) blood pressure at the initial clinic
      visit, average of all BP readings in the 12 months prior to the chart review (the
      measure of current control), antihypertensives prescribed at the most recent
      visit, and patient sociodemographic variables. The mean age of the sample was
      61.6 +/- 12.8 years, and 67% were female. Average 12-month SBP and DBP were 141
      +/- 14.7 and 83.6 +/- 8.5 respectively. Forty-nine per cent of patients had SBP
      controlled to < 140 mm Hg, 79.5% had DBP controlled to < 90 mm Hg, and 46% of
      patients achieved the criterion of < 140/90 mm Hg. In logistic regression
      analysis, age, baseline BP, body mass index and ethnicity, but not gender, were
      associated with current control. After adjustment for other covariates, Hispanics
      and Black people were significantly more likely to be in poor control than whites
      (ORHISP = 2.05, 95%Cl = 1.57-2.70; ORBlack = 1.48, 95%Cl = 1.21-1.81). Twelve per
      cent of patients were not receiving any antihypertensive medication. Of the
      remaining, the majority (52%) were on monotherapy. In the monotherapy group, 45%
      had SBP > or = 140 mm Hg and 16% had DBP > or = 90 mm Hg. We conclude that the
      achievement of new treatment recommendations will require education of primary
      care providers in more aggressive titration of antihypertensive medications to
      control SBP.

PMID- 8872820
TI  - Awareness and treatment of arterial hypertension in Poland.
AB  - In order to find out the general public's opinion on blood pressure (BP) control
      in Poland a poll was conducted on a representative sample of 2080 randomly
      selected subjects. Overall 71% of the subjects were aware of their BP level. The
      awareness of BP level increased progressively with age and education level. Among
      those who were aware of their BP level, 21% had hypertension. Only 43% of
      hypertensives were treated on a regular basis. Cigarettes were smoked by 33% of
      the patients. Only 16% of the hypertensives used a low-salt diet, and only 31%
      tried to reduce animal fat in their diet. More than a half of the hypertensives
      did not adjust their lifestyle and daily habits to the disease. In conclusion,
      these results indicate that the prevention and treatment of hypertension in
      Poland should be urgently improved.

PMID- 8872821
TI  - Survey of cardiovascular risk factors in newly arrived Yemenites to Israel.
AB  - Blood pressure (BP), glucose and lipid profile were examined in 108 adult
      Yemenite immigrants within a few weeks after their arrival in Israel. Mean
      systolic BP was 105.8 +/- 15.21 mm Hg and mean diastolic BP was 69.74 +/- 12.25
      mm Hg. Glucose was 81.4 +/- 30.49 mg/dl; total cholesterol was 167.54 +/- 44.54
      mg/dl and triglycerides 137.11 +/- 94.9 mg/dl, while the small size of the group
      preclude drawing definitive conclusions, it can be said that BP as well as lipids
      level in this group were lower than in Yemenite immigrants who stepped off the
      magic carpet more than 45 years ago.

PMID- 8872822
TI  - The prevalence and awareness of hypertension among Israeli Arabs.
AB  - The prevalence and awareness of hypertension among Israeli Arabs was evaluated by
      measuring blood pressure (BP), heart rate, height and weight in a group of 412
      subjects, 176 women and 236 men, mean age 38.4 +/- 18 (range 12-87 years)
      residing in Northern Israel. All subjects completed a questionnaire that included
      medical and family history and habits. Hypertension was defined when the subject
      used antihypertensive treatment or measured systolic BP was > 140 mm Hg and/or
      diastolic BP was > 90 mm Hg. BP was related to age, body mass index, gender,
      place of living (urban or rural), tobacco use, and level of physical activity. It
      was not related to coffee and alcohol use, and dietary sodium. The prevalence of
      hypertension in this group was 26.7%, similar to that in the general Israeli
      population. Only 9.7% were aware of their hypertension. The level of unawareness
      was significantly higher in the urban dwellers than in rural dwellers: 20.7% vs
      12.8% (P < 0.05). This especially high rate among urban dwellers should be taken
      into account in designing screening programmes to detect hypertension in this
      population.

PMID- 8872823
TI  - Is the pathogenesis of hypertension different in black patients?
AB  - There is a higher prevalence of hypertension in the urban black population of
      South Africa and the USA in comparison to whites living in the same geographical
      areas. Several factors including age, urbanisation, socioeconomic status and
      acculturation contribute to the differences in the prevalence of hypertension
      between blacks and whites. In addition there may be a genetic element.
      Biochemical differences in the lipid profile of the blacks in Sub-Saharan Africa
      may play an Important role in the lower incidence of coronary heart disease.
      Blacks have an abnormal transport mechanism of sodium. There are varying
      responses to antihypertensive drugs in blacks compared to whites. It is probable
      that with a better understanding of the pathogenesis of hypertension in blacks,
      we will be able to reduce the high prevalence, prevent complications and
      institute more effective treatment and control of hypertension.

PMID- 8872824
TI  - Acceptance and side effects of ambulatory blood pressure monitoring: evaluation
      of a new technology.
AB  - Ambulatory blood pressure (BP) monitoring is probably becoming a clinically
      useful procedure for the evaluation of hypertensive patients. Previous reports
      have shown that the devices are safe and serious side effects are rare.
      Discomfort and inconveniences associated with its use are more frequent. In this
      study, patient acceptance of ambulatory blood pressure monitoring (ABPM) was
      compared with acceptance of other diagnostic procedures and their side effects
      were assessed. Patients were asked to fill in a form and 129 of 166 patients
      responded. The acceptance was measured with a visual analogue scale which ranged
      from 'very annoying' on the left to 'not annoying at all' on the right. All forms
      were collected anonymously. Mean distance (cm) of the visual likert scale was 8.6
      to 9.4 for the diagnostic procedures frequently used in routine patient care.
      Ambulatory BP measurement (ABPM) scored 6.1 cm. Reported side effects (in 27% of
      patients) were: plan (9%), skin irritation (8%), noisy device (8%), inconvenience
      with work (3%), haematoma (2%) and other (4%). Reports from the patients on sleep
      quality were: 23% normal, 61% minor disturbance, 14% had sleep, and 2% did not
      sleep at all. It can be concluded that ambulatory BP monitoring was the
      diagnostic procedure with the lowest patient acceptance. Side effects of this new
      technology were reported by 27% of patients. However, risks are relatively minor.
      Sleep disturbances were very frequent and was a serious problem for 16% of
      patients.

PMID- 8872825
TI  - Ambulatory blood pressure monitoring in hemodialysis patients.
AB  - The aim of our study was the detection of blood pressure (BP) variability during
      a dialysis session and in the interdialytic period in normotensive and
      hypertensive hemodialysis (HD) patients using ambulatory blood pressure
      monitoring (ABPM). Twenty-two HD patients aged 54 (range, 33-78) years who were
      on HD for a mean of 17.7 (range, 1-70) months were studied. Twelve patients were
      hypertensives, while the remaining 10 were normotensives (BP < 140/90 mm Hg). In
      all patients ABPM was performed for a total of 48 h including an HD session. A
      significant decrease in systolic BP, diastolic BP and mean BP was observed at the
      end of a dialysis session in hypertensive HD patients. However, in only five
      patients a reduction of more than 5% In mean arterial BP was noticed. No
      significant differences were observed in the BP values between the first and the
      second day after the HD in hypertensive HD patients. Interdialytic BP (both
      systolic and diastolic) was significantly higher than the postdialysis BP
      measured either in the clinic or with the ABPM in these patients. Normotensive HD
      patients exhibited a normal diurnal variation of BP during the first day after
      the HD session (decrease in BP during the night). On the second day after the HD
      session an increase in BP (mainly of systolic BP), as well as a loss of diurnal
      variation were observed. On the contrary, hypertensive HD patients did not
      exhibit the normal diurnal variation of BP during the first or the second day
      after the HD session. Hypertensive HD patients exhibited increased daytime and
      night time BP loads. On the other hand, normotensive HD patients presented with
      BP loads within normal limits, even though a small increase in these loads was
      observed on the second day after dialysis. In conclusion, while hypertensive HD
      patients present a loss of the normal diurnal variation of BP, normotensive HD
      patients exhibit normal variation during the first day after the HD session. The
      loss of the diurnal variation during the second day in these patients suggests a
      volume-dependent state.

PMID- 8872826
TI  - The influence of working time on the diurnal variation of blood pressure.
AB  - The aim of this study was to compare the diurnal blood pressure (BP) profile in
      the same persons performing the same work at different hours: at first
      examination: 06.00 to 14.00 day hours; the second examination: 22.00 to 06.00
      night hours. The study group consisted of 20 men working in a power station. They
      were all doing similar work at the same working place (the handling of electric
      generators). In each subject 24 h BP monitoring (Excel Oxford Medical) was
      performed twice, during day and night working hours. Only eight subjects (40%)
      had a similar diurnal BP profile during both examinations. The BP profile of the
      other 12 subjects (60%) showed distinct differences. However, we have not
      observed any common or characteristic pattern in them. These results suggest that
      the time of working may be an important factor changing the diurnal variation of
      BP. To ascertain why it is not true for all examined subjects needs further
      exploration.

PMID- 8872827
TI  - Ambulatory blood pressure monitoring in normotensive pregnant women.
AB  - Ambulatory blood pressure monitoring (ABPM) provides a profile of blood pressure
      (BP) during daily activities and sleep and could uncover the inter-individual
      variability of BP. The aims of this study were to establish the normal values of
      the ABPM during the three trimesters of normal pregnancy, and to compare these
      values with those obtained in the office. ABPM was carried out on 22 normotensive
      pregnant women. BP values were compared with those obtained in the office. BP
      during the third trimester was significantly higher than the BP recorded during
      the first two gestational periods. In the three trimesters of pregnancy mean
      ambulatory systolic and diastolic BP were lower than the BP measured in the
      office in lying and standing positions. On the other hand, mean ambulatory BP
      (systolic and diastolic) measured during daily activities was not significantly
      different from the BP measured in the office. Sleeping BP was significantly lower
      than waking values in all trimesters, while there were not significant
      differences in the degree of BP fall among the three trimesters. Six women were
      sequentially studied during the three trimesters of pregnancy and particularly at
      the 12, 24 and 32 weeks of pregnancy. In these women, a small but significant
      rise in mean 24 h systolic and diastolic BP was observed at 32 weeks of
      pregnancy. Sleeping BP was significantly lower than waking values in the three
      trimesters. No significant difference in the degree of BP fall on the three
      gestational dates was found. It is concluded that ABPM is a useful tool for the
      evaluation of BP variability during pregnancy. During normal pregnancy ambulatory
      BP levels are highest in the day and lowest at night at all gestational ages and
      increased at the third trimester of pregnancy compared to the values observed
      during the first two gestational periods.

PMID- 8872828
TI  - Ambulatory daytime blood pressure in relation to age and gender compared to
      previous population studies based on office blood pressure. The Danish Study
      Group on Ambulatory Blood Pressure.

PMID- 8872829
TI  - Obesity-related hypertension: its physiological basis and pharmacological
      approaches to its treatment.
AB  - Obesity-related hypertension is a common pathological disorder that can occur at
      any age and in any sex or race. Some of the metabolic, endocrinologic,
      adrenergic, and hemodynamic changes associated with this condition are reversed,
      in part, by weight reduction, which coincidentally decreases blood pressure (BP)
      in obese hypertensive patients. However, a major problem for obese hypertensives
      is dietary noncompliance. Consequently, a pharmacologic approach to obesity
      related hypertension that meets the specific requirements of this complex
      pathological condition should be recommended when the initial nonpharmacological
      approach falls. Diuretics and beta-adrenergic blocking agents have been shown to
      be effective in decreasing BP in obese hypertensives, but they also decrease
      insulin sensitivity and increase cholesterol and lipoprotein concentrations.
      Calcium channel blockers, alpha 1-adrenoreceptor blocking, and angiotensin
      converting enzyme inhibitor agents may offer an efficient and safe
      antihypertensive approach in obese hypertensive patients.

PMID- 8872830
TI  - Prevalence of obesity in Greek hypertensives.
AB  - An association of obesity and hypertension is well recognised and there is a
      direct positive relationship between body weight or body mass index (BMI) and
      blood pressure (BP), although the mechanisms responsible for weight-related
      increases of BP are still unknown. Obesity does appear to be an independent risk
      factor for premature mortality, especially when it is associated with other risk
      factors such as hyperinsulinemia and glucose intolerance (or diabetes),
      hyperlipidemia, and hypertension. However, there are differences among racial and
      ethnic subgroups. The aim of our study was the investigation of the prevalence of
      obesity and its severity among Greek hypertensive patients in comparison to
      normotensive controls. We have studied a large enough sample of Greek
      hypertensives consisting of 1101 patients (504 male/597 female, 23-85 years of
      age) and 242 normotensive controls (136 male/106 female, 23-75 years of age). In
      all patients and normotensive controls BMI (ie weight/height in 2mm) was
      measured, as well as the waist-to-hip (W/H) ratio. A BMI of less than 27 was
      accepted as normal, a BMI of 27-32 as indicating mild to moderate obesity, a BMI
      of 32-37 as an index of severe obesity, and a BMI > 37 as a measure of very
      severe obesity. Obesity in hypertensive patients was more frequent than in
      normotensive controls (62.5% vs 54.2%, P = 0.024), and hypertensive women were
      more commonly obese than hypertensive men (67.16% vs 56.8%, P = 0.002). Severe
      and very severe obesity was more common in hypertensive women than in men (20.7%
      vs 9.68%, P < 0.001, and 8.1% vs 0.52%, P < 0.0001, respectively), although
      obesity of severe and very severe degree was equally found in hypertensives and
      normotensives of both sexes. BMI of all hypertensives was significantly greater
      in comparison to that of normotensives (30.13 +/- 0.44 vs 26.74 +/- 0.76, mean +/
      s.e., P < 0.0001); W/H ratio of hypertensives was significantly greater than
      that of normotensives, indicating more frequent central obesity in hypertensives.
      We conclude that obesity in Greek hypertensive patients is more frequent than in
      normotensive controls, while hypertensive women have more severe obesity than
      hypertensive men, and are more frequently obese than men.

PMID- 8872831
TI  - Follow up of young people with high casual blood pressure.
AB  - High blood pressure (BP), often borderline hypertension, can be also found in
      adolescents. In these subjects the haemodynamic pattern, high cardiac output and
      normal vascular resistance, differs from that of older hypertensives. Although
      the risk for hypertension is higher in this group than in the general population,
      only a minority of them will develop sustained hypertension later in life. They
      can therefore be viewed as an enriched pool of future hypertensives but not as
      true prehypertensives. The aim of this longitudinal study was to analyse the
      relation between casual BP measured in high school students and in the same
      subjects 3 years later. In 1990, an extensive study on BP was carried out in 1062
      high school students aged 18 years. Sitting BP, heart rate, weight, and body mass
      index (BMI) were measured in each subject. After 3 years, the 50 subjects with
      the highest BP level recorded in 1990 were recalled. Forty-five subjects (90%, 30
      males and 15 females) agreed to undergo a second examination. They were seen as
      outpatients in the Hypertension Centre of our institute. BP was measured with a
      mercury sphygmomanometer after a 10 min rest three times in 5 min. Systolic and
      diastolic BP were significantly reduced after 3 years (137 +/- 13 vs 132 +/- 10 P
      = 0.002; 92 +/- 4 vs 85 +/- 6 P = 0.0001, mm Hg). By means of a multiple
      regression test, including parameters recorded in 1990, systolic blood pressure
      (SBP) (R = 0.53 Slg F = 0.0002) and diastolic blood pressure (DBP) (R = 0.60 Slg
      F = 0.0001) were shown as the main determinants of SBP, while DBP was related
      only to previous BMI (R = 0.37 Slg F = 0.01). The reduction of both SBP and DBP
      after 3 years could be explained either by a true, spontaneous decrease of BP or
      as a consequence of different environmental conditions during the second
      examination (more prolonged resting time, repeated measurements). However, data
      of this study demonstrate that casual SBP and DBP are the main determinants of
      future SBP, thus confirming the prognostic value of casual BP measurement in
      young people. Moreover, our data emphasises the role of BMI as the main
      determinant of future high DBP.

PMID- 8872832
TI  - Blood pressure and anthropometry in parents and children of a southern Italian
      village.
AB  - In an investigation on hypertension risk factors, the entire school population
      was examined in Trecchina, a southern Italian village. The reported findings
      refer to those children examined together with at least one parent, for a total
      of 134 mother-child pairs and 128 father-child pairs. For these groups of
      children, fathers and mothers, systolic (SBP) and diastolic (DBP) blood pressure,
      weight (W), height (H) and triceps skinfold (TS) were detected and body mass
      index (BMI) was calculated in order to evaluate the prevalence of high blood
      pressure (BP) values and if overweight. Of 19.3% children, 26.9% fathers and
      15.8% mothers showed high BP values; 28.9% of children, 14.0% of fathers and
      19.3% of mothers were overweight. In children, the analysis of correlations,
      after adjustment for height, showed a significant association between BP and W,
      BMI and TS. Using multiple regression analysis, with BP as the dependent
      variable, SBP was significantly associated with BMI and age in mother and
      fathers. For DBP the only variable entered in the model was BMI for mothers and
      fathers. When controlling for the children's age, H, W and BMI of children were
      significantly related to H, W and BMI of mothers and fathers. These results
      confirm that overweight and a parental history of obesity are predictive and
      possibly causal factors for essential hypertension.

PMID- 8872833
TI  - Blood pressure response to exercise in young subjects with and without parental
      history of hypertension.
AB  - We examined 150 young male adults in the Italian Air Force to evaluate the
      correlation between blood pressure (BP) response to bicycle exercise and early
      structural changes of the left ventricle and the carotid arteries. The subjects
      were divided into three subgroups: (1) borderline hypertensives; (2)
      normotensives having one or both parents with hypertension; (3) normotensives
      without family history of hypertension. All subjects underwent a submaximal
      exercise test, echocardiography and carotid ultrasonographic study. The
      echocardiographic examination showed no significant difference between the three
      subgroups, while the vascular ultrasonographic examination showed a significant
      difference in carotid thickness between borderline hypertensives and the two
      other groups. The exercise test induced an abnormal hypertensive response only in
      the borderline group. We also considered the variation of systolic BP between
      maximum stress and the 1st, 3rd, 5th and 8th minute of recovery phase. From our
      data it seems that more than the exercise test, recovery BP values may be
      suggestive of an exaggerated cardiovascular response.

PMID- 8872834
TI  - Metabolic, humoral and haemodynamic characteristics of normotensive offspring
      from hypertensive families.
AB  - Arterial hypertension is not only a haemodynamic abnormality, but it is
      associated with several metabolic and humoral changes. Heredity appears to be
      participating in the pathogenesis of essential hypertension (EH). We studied
      whether some metabolic, humoral and haemodynamic changes could be detected in
      genetically predisposed normotensive sons of hypertensive families (SH) compared
      with normotensive sons of normotensive parents (SN). The study groups consisted
      of 40 young SN and 40 SH matched for age and body mass index (BMI). Blood samples
      for laboratory determination were taken under basal conditions and 90 min after a
      75 g glucose load. SH already had a higher systolic blood pressure (BP) (120.7 +/
      1.7 mm Hg) and a tendency to a higher diastolic BP than the SN group. In spite
      of the fact that both basal and stimulated glycemia did not differ significantly
      between the study groups, significantly higher glucose-stimulated immuno-reactive
      insulin (IRI) was found in SH (80.1 +/- 7.06 vs 62.9 +/- 5.76 uU/l). Higher
      plasma concentration of catecholamines in SH indicate their higher sympathetico
      adrenal activity. The groups did not differ significantly in basal and stimulated
      plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP).
      There was a tendency for higher levels of endothelin (ET) in the plasma of SH.
      The glucose load increased as expected, glycemia, IRI and C-peptide, but ANP and
      ET concentrations were unexpectedly reduced. These abnormalities were associated,
      in SH, with higher left ventricle (LV) mass index and impaired diastolic filling.
      Persistence of high LV mass index, even after adjustment for respective systolic
      BP, suggests the participation of more than haemodynamic stress in the increase
      of LV mass. Our results suggest that in normotensive genetically predisposed
      subjects from hypertensive families, some metabolic and humoral abnormalities can
      already be detected. They might be responsible for the higher BP readings with
      subsequent manifestations of hypertension and LV morphological and functional
      abnormalities.

PMID- 8872835
TI  - Hypertension and atherosclerosis.
AB  - A minimum level of blood pressure is necessary for atherosclerosis to develop,
      even in the presence of hypercholesterolemia. Experimentally and clinically we
      have both examples of atherosclerosis in which hypercholesterolemia is the
      dominant pathogenetic factor and others in which hypertension prevails (BBWT).
      The pathogenetic role of hypertension may be direct (wall stress) or mediated
      through humoral factors which characterize the different types of hypertension
      (renin, angiotensin, cathecholamines, endothelin, aldosterone). Probably,
      different forms of atherosclerosis will be identified in the future, with a
      different prognosis and therapeutical approach.

PMID- 8872836
TI  - Risk factors leading to coronary heart disease among the black, Indian and white
      peoples of Durban.
AB  - This paper compares and contrasts the important risk factors which may predispose
      to coronary heart disease (CHD) in the Black, Indian and White peoples of Durban.
      CHD is very common the Whites and Indians in South Africa. In contrast CHD is
      still uncommon in the Blacks of South Africa. Indians living in South Africa have
      a higher prevalence of CHD compared to Indians in India.

PMID- 8872837
TI  - Circadian blood pressure changes and cardiac geometry in essential arterial
      hypertension.
AB  - To study a relationship between ambulatory blood pressure (BP) and left
      ventricular geometry in mild to moderate arterial hypertension, 24 h ambulatory
      blood pressure monitoring (ABPM) at half-hourly intervals in the daytime and
      hourly at night (Spacelabs 90207) and echocardiographic examinations were
      performed in 60 hypertensives aged 42 +/- 7.9 years and in eight normotensives.
      The patients were subdivided into four groups according to the relative wall
      thickness (RWT) and left ventricular mass index (LVMI). Concentric remodelling
      was identified on the basis of increased RWT, eccentric hypertrophy in case of
      increased left ventricular mass, and concentric hypertrophy when both parameters
      were increased. Group I consisted of 15 patients with normal left ventricle;
      group II, 19 patients with concentric remodelling; group III, 7 patients with
      eccentric hypertrophy; and group IV, 19 patients with concentric hypertrophy.
      Analysis of correlations of maximal and mean systolic (SBP) and diastolic BP
      (DBP) values and BP variability with left ventricular mass and relative wall
      thickness revealed the strongest correlation in group IV between concentric
      hypertrophy and peak SBP in the entire 24 h and in the daytime, mean SBP in the
      daytime and SBP variability in the entire 24 h. No significant correlations were
      found in groups I, II, III or controls. In conclusion, SBP variability assessed
      non-invasively with ABPM correlates positively with left ventricular mass. BP
      variability seems insignificant for left ventricular geometry.

PMID- 8872839
TI  - Family history of cardiovascular diseases and risk factors in children.
AB  - A sample of 861 Roman children, aged 7 to 14 years, was investigated in order to
      evaluate the association between some cardiovascular risk factors such as high
      systolic (SBP) and diastolic (DBP) blood pressure levels, body mass index (BMI),
      arm fat area (AFA) and a history of diabetes, stroke, angina pectoris, myocardial
      infarction, hypertension and overweight in their parents. The sample investigated
      was subdivided into three subgroups, based on whether the children had just one
      parent, both parents or no parent with a positive history. For all the variables
      considered, the highest values were found in the group of children with a
      positive history for both parents and the lowest ones in children with a negative
      history for both parents. The analysis of significance, based on the mean values
      for the three groups, revealed statistically significant differences for SBP,
      DBP, BMI and AFA between the group of children with a positive history for both
      parents and that of children with a negative history for both parents.
      Significant differences also emerged for DBP, BMI and AFA between the mean values
      of children positive for one parent and those negative for both parents and for
      BMI and AFA between the means of children positive for one parent and those
      positive for both parents. The odds ratio of high systolic and/or diastolic BP,
      BMI and AFA levels was consistently higher in children with one or two parents
      with a positive history compared to children with both parents with a negative
      history, and even higher considering only children with both parents with a
      positive history vs children with both parents with a negative history.

PMID- 8872838
TI  - Differences in response to nutrition and fitness education programmes in relation
      to baseline levels of cardiovascular risk in 10 to 12-year-old children.
AB  - OBJECTIVE: To examine associations between children's responses to nutrition and
      fitness programmes and their baseline levels of cardiovascular risk factors.
      DESIGN: A randomised controlled trial. SETTING: Primary schools in Perth, Western
      Australia. PARTICIPANTS: 1147 children aged 10-12 years. INTERVENTIONS: Fitness,
      fitness+school nutrition, school +home nutrition or home nutrition programmes and
      a control group. MAIN OUTCOME MEASURES: Blood pressure (BP), cholesterol,
      nutrient intake, fitness, and body fat. RESULTS: Fall in systolic BP was
      significantly greater in the higher risk groups with the fitness intervention for
      boys and the home nutrition intervention for girls. Overall, diastolic BP fell
      for girls in the fitness intervention with no differences related to cluster
      membership. Higher risk boys in the fitness intervention showed greater
      improvement in fitness than the lower risk boys. Fitness improved in girls in the
      fitness programme but responses did not differ significantly according to cluster
      membership. Decrease in triceps skinfolds was significantly greater for higher
      risk boys in the home nutrition group and in higher risk girls except for those
      receiving the school+home nutrition intervention. Home nutrition programmes were
      associated with decreased intake of fat and greater intake of fibre in girls in
      the higher risk group and of sugar in higher risk boys. CONCLUSIONS: The greatest
      improvement in the higher risk children were associated with fitness and home
      nutrition programmes. Health education programmes aiming to include higher risk
      children should focus on these areas.

PMID- 8872840
TI  - Microalbuminuria as an early marker of severity in hypertensive pregnant women.
AB  - The value of microalbuminuria in predicting hypertensive complications in
      pregnant patients at high risk was tested in a prospective trial. A total of 276
      patients were studied (142 in the study group vs 134 controls). Albumin was
      measured in 8-h overnight urine collection throughout pregnancy using
      radioimmunoassay technique. The pregnant women, in both the study and control
      groups demonstrated a statistically significant increase in albumin excretion
      rate in the second and third trimester compared with the first. Using logistic
      and linear regression models, the presence of microalbuminuria in the early third
      trimester was proven to be predictive of severe disease (odds ratio 2.1,
      confidence interval (CI) 1.26-3.53) and birth weight (R2 = 0.7, P < 0.05) in the
      study group. Intrauterine growth retardation and neonatal outcome were less
      predictable. With the introduction of radioimmunoassays, we believe severe
      disease can be predicted by detecting microalbuminuria in the early third
      trimester of pregnancy in high risk patients.

PMID- 8872841
TI  - Hostility, aggression and the association with hypertension in post-menopausal
      women.
AB  - In order to determine whether a hostile attitude is associated with hypertension
      in post-menopausal women, we conducted a cross-sectional study of a sample of
      post-menopausal women enrollees from the Group Health Cooperative (Seattle,
      Washington). Out-patient medical records were reviewed for all subjects.
      Hypertension was defined as a recorded diagnosis of hypertension and treatment
      with an anti-hypertensive drug. Borderline hypertensives were excluded. Women
      were interviewed by telephone and asked the 14 questions comprising the Hostile
      Affect (HOS) and Aggressive-Responding (AGGR) factors of the Cook-Medley
      hostility scale. Scores were grouped into high vs low HOS and AGGR. The AGGR
      score was available for 430 hypertensives and 628 normotensives. The HOS score
      was available for 436 hypertensives and 616 normotensives. High AGGR scores had a
      borderline association with hypertension (Odds Ratio (OR) = 1.26; 95% Confidence
      interval (CI) = 0.97-1.62). HOS was not associated with hypertension. Adjusting
      for age, physical activity, diabetes mellitus, cholesterol level, tobacco and
      alcohol use, weight and race, changed the association of AGGR with hypertension
      only slightly (OR = 1.22; CI = 0.92-1.63). We found a weak association between
      the prevalence of treated hypertension and AGGR in post-menopausal women. There
      was no association between the HOS component and hypertension. The results of
      this study support the need for prospective studies of the role of psychological
      factors in the development of hypertension in post-menopausal women. If this
      association is confirmed, AGGR measures may help identify women at high-risk who
      are most likely to benefit from hypertension screening and primary prevention.

PMID- 8872842
TI  - Heterogeneous patterns of sodium excretion during sodium restriction in essential
      hypertensive patients.
AB  - OBJECTIVE: To study the sodium excretory pattern by which sodium balance is
      reached. METHODS: Ninety untreated essential hypertensives with a median age of
      47 (range: 18-70 years) were admitted to a metabolic ward for 7 days and put on a
      sodium diet of 55 mmol/day. During these 7 days urinary excretions of sodium,
      potassium and creatinine were determined daily along with mean arterial pressure
      (MAP) and weight. RESULTS: Changes in urinary sodium excretion were not uniform,
      but according to the pattern of attaining sodium balance, subjects could be
      divided into four groups. Group 1 (n = 31) gradually reached sodium balance,
      whereas group 2 (n = 10) showed an abrupt fall in sodium excretion on the third
      day and an extremely fluctuating sodium excretion thereafter. Group 3 (n = 32)
      reached sodium balance on day four, but displayed a rise in sodium excretion
      during the following days and group 4 (n = 17) attained sodium balance only very
      slowly or not at all. Compared to the other groups, group 4 lost more sodium and
      at the same time displayed a greater fall in blood pressure. CONCLUSIONS: Our
      data suggest that there may be at least four different patterns by which sodium
      balance can be reached following a reduction in sodium intake. The determinants
      of these responses remain, however, elusive.

PMID- 8872843
TI  - Sodium sensitivity of blood pressure in hypertensives is not related to sodium,
      but rather to renin.
AB  - OBJECTIVE: To investigate whether a certain degree of sodium-sensitivity of blood
      pressure (BP) in essential hypertensives during sodium restriction is related to
      cumulative sodium loss. METHODS: One-hundred and seventeen untreated essential
      hypertensives were admitted to a metabolic ward for 7 days and put on a sodium
      restricted diet of 55 mmol/day. During these 7 days urinary excretions of sodium,
      potassium and creatinine were determined daily along with mean arterial pressure
      (MAP) and weight. Active plasma renin concentration (APRC), aldosterone (ALDO),
      renal plasma flow (RPF) and plasma volume (PV) were assessed after 7 days under
      steady state condition. The population was divided into tertiles based on the
      final changes in BP after 7 days. RESULTS: Textile 1 displayed a median fall in
      MAP of -13 (-42 to -9) mm Hg, whereas in tertile 2 and 3 a fall of -6 (-9 to -4)
      mm Hg and a rise of +1 (-3 to +11) mm Hg respectively, was encountered. Baseline
      characteristics were comparable between the tertiles. When tertile 1 was compared
      to tertile 3 no significant differences between these tertiles were found with
      respect to cumulative sodium and potassium balances and weight loss. Furthermore,
      APRC levels were significantly higher in tertile 3 as compared to tertile 1 (22
      and 27 mU/l, respectively). Renal vascular resistance (RVR) tended to be higher
      in tertile 3, although this was not statistically significant. Aldo, RPF and PV
      were comparable between the tertiles. CONCLUSIONS: In contrast with tertile 1,
      MAP in tertile 3 is maintained at its original level, despite comparable sodium
      losses. In tertile 3, however, levels of renin are higher compared to the group
      that is more sodium-sensitive. Therefore, our data suggest that the degree of
      sodium-sensitivity of BP in essential hypertensive subjects is not determined by
      sodium status, but rather by renin.

PMID- 8872844
TI  - A 5-year follow-up of preventive approach to patients with essential
      hypertension.
AB  - We examined the effect of a 4-5 week spa programme consisting of hypertension
      control education, physical education and smoking cessation on a long-term risk
      factor control. Two hundred and twenty hypertensive males underwent a 1 month
      training programme. At the end of the month, improvement had occurred in blood
      pressure (BP), heart rate (HR) exercise capacity, degree of obesity and serum
      cholesterol and triglycerides. At 5-year follow-up several parameters still
      showed improvement. The mean resting, exercise and recovery BP was lower than
      initial values as was the double product. The subjective and objective load
      tolerance during exercise had also improved. Half of the patients required less
      medication than initially to control their BP and in 80% of cases the BP was
      either the same or lower than initially. The mean heart size did not change from
      control values; 84% of patients felt that their general health improved. The mean
      triglyceride level was lower than at the start and the number of smokers had
      fallen from 33 to 21%. On the other hand several parameters showed disappointing
      results. The weight and serum cholesterol and risk factor score remained
      unchanged and mean resting HR actually increased. Only 10% were exercising
      regularly and 20% had a worsening of their BP. Thus intensive short term
      intervention studies may help reduce some cardiovascular risk factors temporarily
      but the long effect of this intervention in the control of risk factors is still
      limited.

PMID- 8872845
TI  - Repeated fasting and refeeding with 20:5, n-3 eicosapentaenoic acid (EPA): a
      novel approach for rapid fatty acid exchange and its effect on blood pressure,
      plasma lipids and hemostasis.
AB  - Twenty hypertensive subjects participated in three clinical trials of 13 days
      each, to examine the effects of Alsepa fish oil [20:5, n-3 eicosapentaenoic acid
      (EPA) 180 mg, and 22:6 n-3 docosahexaenoic acid (DHA) 120 mg] on n-3 for n-6
      polyunsaturated fatty acids (PUFA) exchange on serum phospholipids, blood
      pressure (BP), triglycerides (TG) and primary hemostasis. After 13 days, plasma
      phospholipids showed an increase in sigma n-3 (EPA and DHA) from 2.0 to 5.9% (P <
      0.01), and a decrease in sigma n-6 (arachidonic acid and linoleic acid) from 29.8
      to 22.6% (P < 0.01). A concomitantly significant reduction in systolic BP (SBP)
      (158.7 +/- 23.8 mm Hg to 146.5 +/- 17.0 mm Hg, P = 0.04), and diastolic BP (DBP)
      (80.8 +/- 8.4 mm Hg to 72.9 +/- 14.9 mm Hg, P = 0.04) as well as a significant
      decrease in platelet adhesion and aggregation on extra cellular matrix measured
      as a percentage of surface coverage (11.9 +/- 4.8% to 4.2 +/- 3.2%, P = 0.0001)
      was observed. In addition, a significant reduction in baseline dependent TG was
      observed; the higher the baseline level TG, the more pronounced the reduction
      (average 159.2 +/- 74.6 mg% to 108.0 +/- 46.1 mg%, P = 0.001). No change was
      observed in total cholesterol, high and low density lipoprotein (HDL, LDL),
      platelet and fibrinogen. Repeated fasting and refeeding with fish oil facilitated
      plasma exchange of n-3 for n-6 PUFA, improved BP, clinical metabolic parameters
      and lowered platelet reactivity in the vessel wall (primary hemostasis). In
      severe and life-threatening situations, the beneficial effects of fish oil should
      be considered for rapid exchange of n-3 for n-6 PUFA. In this study we describe a
      novel approach for rapid fatty acid exchange by fasting/refeeding with fish oil
      supplementation, as well as improved BP, plasma lipids and primary hemostasis.
      Further research is required on the therapeutic use of fish oils and the
      physiological mechanisms involved in fatty acid exchange.

PMID- 8872846
TI  - High-altitude pulmonary hypertension: effects of captopril on pulmonary and
      systemic arterial pressures.
AB  - The purpose of investigation was the assessment of the effect of captopril on
      both systemic (Pa) and pulmonary arterial pressures (PPA) in patients with high
      altitude pulmonary hypertension (HAPH). Seventeen patients (mean age 44 +/- 6.8
      years) with HAPH and mild-to-moderate systemic arterial hypertension were
      included in the study. All the patients underwent right heart catheterization
      with measurements of systolic PPA (PPA,syst), mean PPA (PPA) and diastolic PPA
      (PPA,diast). After a 4 week placebo phase, patients with PPA,syst > 25 mm Hg, PPA
      > 15 mm Hg and systemic diastolic blood pressure (Pa,diast) > 100 mm Hg received
      captopril (50-75 mg at 08.00) for a period of 12 weeks. The statistical
      evaluation of the results were made using the Student's t-test. It was found that
      captopril significantly decreases PPA and Pa.

PMID- 8872847
TI  - Efficacy of different antihypertensive drugs in the emergency department.
AB  - Hypertensive crises are a commonly observed problem in an emergency department.
      The aim of the study was to evaluate the efficacy and safety of different
      antihypertensive agents in the treatment of patients with hypertensive crises.
      168 patients (mean age: 52 +/- 12 years) admitted to the emergency department
      with a hypertensive urgency (systolic (SBP) blood pressure > 210 mm Hg and/or
      diastolic (DBP) blood pressure > 110 mm Hg) or a hypertensive emergency (DBP >
      100 mm Hg and evidence of end-organ damage) were included into the study
      protocol. Blood pressure (BP) was measured every 5 min automatically using a
      noninvasive BP measurement unit. After a resting period of 30 min the patients
      received the following drugs: 5 mg enalaprilat intravenous (n = 43) or 25 mg
      urapidil intravenous (n = 48) or 10 mg nifedipine-capsule sublingual (n = 47) or
      2 x 5 mg nifedipine-spray sublingual (n = 30). The aim of treatment was to reduce
      SBP below 180 mm Hg and DBP below 95 mm Hg within 45 min after start of
      treatment. When evaluating the response rates the highest rate was observed in
      the urapidil group (96%). The response rate of enalaprilat and both preparations
      of nifedipine were similar (70-72%). The rate of major side effects was higher in
      the urapidil compared to the other drugs (4% vs 2% in the nifedipine-group or 0%
      in the enalaprilat-group). All four drugs are suitable in the treatment of
      patients with hypertensive crisis in the emergency department. Urapidil should be
      used as a first choice drug in critically ill patients with hypertensive crisis
      due to its higher response rate.

PMID- 8872848
TI  - The effects of diuretics on quality of life of hypertensive patients.
AB  - OBJECTIVES: To study the effect of diuretics and diuretics discontinuation on the
      quality of life (QOL) of hypertensive patients. METHODS: 149 beta blocker treated
      mild to moderate hypertensive patients were included in the study. Seventy-three
      were treated by beta blockers (BB's) only and 60 by BB's and diuretics, for 40
      patients diuretics was discontinued. Physical symptoms and QOL were assessed
      before and 9-15 months after the change in treatment. RESULTS: At baseline,
      subjects on diuretics experienced more gastrointestinal symptoms, weakness, and
      sex related problems; and their QOL was poorer. At the end of the follow-up,
      patients on diuretics scored poorest on physical strength items and on health
      perceptions; those who were never treated by diuretics scored best; and those who
      stopped were in between. CONCLUSIONS: Diuretics treatment adversely affect
      patients' QOL. Cessation of diuretics treatment for at least 9 months improved
      some aspects of patients' QOL, though those who never received diuretics were
      better of than others.

PMID- 8872849
TI  - Efficacy of low felodipine dose monotherapy in mild-to-moderate hypertension: a
      comparison between office and ambulatory blood pressure monitoring.
AB  - The efficacy and tolerability of felodipine, in a low dose of 5-10 mg daily was
      assessed in 32 patients with mild-to-moderate hypertension, aged 53 +/- 11 years.
      The results of office vs 24 h ambulatory blood pressure measurements (ABPM) were
      compared. Inclusion criteria included an office systolic and diastolic blood
      pressure (SBP/DBP) > 140/90 mm Hg and a 24 h ABPM SBP/DBP > 135/85 mm Hg.
      Felodipine was initiated at a dose of 5 mg daily. At day 28 of the study, if
      office DBP > 90 mm Hg, the dose was doubled to 10 mg daily. At the end of the
      study (day 84), 24 h ABPM was done again. Side effects were noted throughout the
      study. Four patients dropped out during the study (two due to headache, one due
      to pedal edema and one rejected further participation). Of the remaining 28
      patients, at day 28, 12 required an increased dose of 10 mg/day. At the end of
      the study, office BP was below 140 90 mm Hg in 71% of the patients. In the whole
      group BP decreased from 158 +/- 15/101 +/- 8.4 to 138 +/- 9/85 +/- 5 mm Hg, P <
      0.001. ABPM showed that BP was normalized in 82% of the patients. It decreased
      from 146.8 +/- 9.56/94.8 +/- 7.4 to 130.2 +/- 10.6/83 +/- 6.3 mm Hg, P < 0.001.
      BP was similarly reduced in working and sleeping hours, with preservation of the
      circadian rhythm. Heart rate was unaffected by the drug. Five patients showed
      persistently elevated SBP on office measurements while on ABPM, the values were
      within normal limits. This finding confirms the existence of a white coat effect
      in patients with proven hypertension and the superiority of ABPM over office BP
      measurements in clinical investigations. In summary, ABPM showed that the
      antihypertensive effect of felodipine was sustained throughout normal 24 h,
      including the critical (as regards cardiovascular morbidity) awakening hours.

PMID- 8872850
TI  - INSIGHT: international nifedipine GITS study intervention as a goal in
      hypertension treatment.
AB  - The objective of the study is to compare fatal and nonfatal cardiovascular
      endpoints in hypertensive patients randomised to the calcium-channel blocker,
      nifedipine GITS or a thiazide diuretic, co-amilozide. A total of 6592 patients
      from nine countries (UK, France, Israel, Spain, Italy, The Netherlands, Sweden,
      Denmark and Norway) will be recruited, aged 55-80 and with a blood pressure (BP)
      > or = 150/95 or > or = 160 mm Hg (systolic). All patients will have at least one
      other major cardiovascular risk factor. Patients will be minimised by country and
      risk factors and randomised to double-blind treatment with either nifedipine GITS
      or diuretic. After a single dose titration, additional treatment will be atenolol
      or enalapril (where beta-blockade is contra-indicated). After achieving a target
      BP of 140/90 mm Hg patients will be followed for a total of 3 years. Primary
      endpoints are myocardial infarction, stroke, subarachnoid haemorrhage, heart
      failure and sudden cardiac death. The study has a power of 80% at 5% significance
      to detect a difference between 8% event rate over 3 years in diuretic-treated
      patients and 6% in those receiving nifedipine.

PMID- 8872851
TI  - Hypertension optimal treatment: the Israeli HOT Study Group. Hypertension Optimal
      Treatment.
AB  - A total of 411 patients were recruited in the Israeli cohort of the Hypertension
      Optimal Treatment (HOT) Study, a multinational study conducted to assess the
      effect on cardiovascular morbidity and mortality in hypertensive patients of
      three levels of target diastolic blood pressure: < 90, < 85, and < 80 mm Hg.
      Initial treatment with felodipine in all patients was supplemented with other
      drugs as needed. When compared to the subjects in the rest of the world, the
      percentage of Israeli patients getting previous antihypertensive treatment was
      higher, reflecting a higher proportion of hospital-recruited patients. This
      accounted for the lower percentage of Israeli patients ending up with low-dose
      felodipine: 50% vs 56% in other countries. The percentage of patients getting
      high-dose felodipine plus additional drugs was also higher: 3.8% vs 2.9% for
      other countries. Felodipine was remarkably well tolerated, and most of the
      patients were able to continue this drug regimen.

PMID- 8872852
TI  - Felodipine in the treatment of severe refractory hypertension.
AB  - The efficacy of felodipine and tolerance of this drug was examined in 52
      patients, 23 men and 29 women, 18-76 years of age, in whom it either replaced
      previous therapies of nifedipine and other vasodilators, or was added to a
      constant dose of beta blockers and diuretics or another previous therapy, which
      was unchanged. Felodipine significantly reduced blood pressure (BP), from 192.3
      +/- 31.9/114.3 +/- 18.0 to 155.7 +/- 19.5/93.8 +/- 11.5 mm Hg, with no change in
      pulse rate. There were no significant biochemical changes, renal deterioration or
      blood sugar disequilibrium. Adverse reactions including flushes and leg edema
      could be tolerated by most of the patients, however six patients dropped out.
      Orthostasis dictated a decrease in felodipine dosage. Felodipine appears to be a
      highly potent, well tolerated drug and offers a substitute treatment for severe
      hypertensives refractory to other vasodilators.

PMID- 8872853
TI  - Prescribing pattern of antihypertensive drugs in the community.
AB  - The selection of the most appropriate therapy for hypertension remains a
      controversial issue. Little information is available regarding the prescribing
      patterns of antihypertensives in the primary care setting in Israel. The use of
      antihypertensives in 200 patients of the Maccabi Health Fund was, therefore,
      examined from April to June 1994. Sixty-four per cent of patients received
      monotherapy and 36% combination therapy. The most commonly prescribed medication
      for monotherapy were angiotensin-converting enzyme (ACE) inhibitors (33.6%),
      followed by beta-blockers (28.1%) and calcium channel antagonists (26.6%).
      Diuretics were prescribed to 7.0% of the patients. Analysis of overall drug
      utilization showed that diuretics were used in 21.5% of patients, beta-blockers
      in 39.5%, calcium channel blockers in 46% and ACE inhibitors in 40% of patients.
      Despite the growing evidence of the benefits of diuretics and beta-blockers, our
      results show a low utilization of these agents in comparison to other countries.
      It may be speculated that the lack of national guidelines, the absence of
      utilization reviews by third party providers as well as differences in patient
      population and climate conditions may all contribute to the current prescribing
      habits of physicians in the Israeli community.

PMID- 8872854
TI  - Are plasminogen antibodies in rheumatoid arthritis of pathogenic significance?

PMID- 8872855
TI  - Genetic analysis of nitric oxide synthase isoforms: targeted mutation in mice.
AB  - Since the discovery that nitric oxide is an endogenous vasodilator responsible
      for endothelium-derived relaxing factor activity, nitric oxide has been found in
      many different cell types and implicated in many diverse biological processes.
      Because pharmacological blockade does not distinguish between the three major
      isoforms of nitric oxide synthase, the tissue and enzyme source of nitric oxide
      is unclear in many situations. Targeted disruption of the genes for the various
      isoforms of nitric oxide synthase offers a useful genetic approach to study the
      roles of each isoform and to examine the effects of their deletion on
      physiological processes in intact animals. Here we review the phenotypes of the
      various nitric oxide synthase mutant mice and examine what they reveal about the
      complexities of the nitric oxide signaling system and about molecular and
      physiological compensations brought into play in the absence of individual
      isoforms.

PMID- 8872856
TI  - Throwing a spanner in the works: antibiotics and the translation apparatus.
AB  - The protein synthetic machinery is essential to all living cells and is one of
      the major targets for antibiotics. Knowledge of the structure and function of the
      ribosome and its associated factors is key to understanding the mechanism of drug
      action. Conversely, drugs have been used as tools to probe the translation cycle,
      thus providing a means to further our understanding of the steps that lead to
      protein synthesis. Our current understanding as to how antibiotics disrupt this
      process is reviewed here, with particular emphasis on the prokaryotic elongation
      cycle and those drugs that interact with ribosomal RNAs.

PMID- 8872857
TI  - Genetics of bladder cancer.
AB  - Bladder cancer manifests many different forms, ranging from superficial to
      aggressive muscle invasion, which suggests that various genetic alterations are
      responsible. Several attempts have been made to establish correlations between
      specific genetic alterations and various grades of the disease. Numerous types of
      chromosomal abnormalities have been observed, involving [1p, 1q, 2q, 3p, 4p, 5q,
      i(5p), +7, +8, 8p, 9p, 9q, 10q23-25, 11p, 11q, +11, 13q, 14q, 17p, 18q, 21q, and
      Y]. In addition, p53 mutations and loss of heterozygosity on various chromosomes
      have recently begun to shed light on the molecular pathways of transitional cell
      carcinomas of the bladder. We have begun to focus on specific genomic sites
      (especially 9q), although the heterogeneity of the disease and the variable
      presentation suggests divergent progression pathways. When the genetic basis of
      bladder cancer is fully understood, new diagnostic and therapeutic strategies
      will be developed, which in turn may promote better clinical management by
      pathologists and urologists.

PMID- 8872858
TI  - Reduced atrial angiotensin receptor type 1 mRNA content in end-stage human heart
      failure: assessment by a novel quantitative PCR-ELISA technique.
AB  - The number of atrial angiotensin II binding sites is reduced in end-stage human
      heart failure. The goals of our study were the development of a quantitative
      polymerase chain reaction for angiotensin II receptor type 1 mRNA to determine
      the angiotensin receptor type 1 (AT1) mRNA content in the atria of patients with
      end-stage heart failure. We established a quantitative PCR based on
      coamplification of AT1 wild-type and an internal standard in the same PCR,
      followed by liquid-phase hybridization of PCR products in microtiter plates and
      quantitation by ELISA. Glyceraldehyde phosphate dehydrogenase mRNA in the same
      samples was used to relate the AT1 mRNA content to a stably expressed reference
      gene. Atrial samples from 11 patients with end-stage heart failure obtained at
      cardiac transplantation were compared with atrial samples from 11 patients with
      normal cardiac function undergoing routine cardiac surgery. A PCR/ELISA system
      with a variance of about 6% after reverse transcription and a linear measuring
      range was established. In the samples from 11 patients with end-stage heart
      failure a 58% decrease in AT1 mRNA content was found in comparison with 11
      controls (heart failure: 185,680 +/- 196,912 AT1 mRNA copies/microgram RNA,
      controls: 440,555 +/- 268,456, P < 0.02). When AT1 mRNA content was related to
      glyceraldehyde phosphate dehydrogenase mRNA, a 65% decrease was detected
      (AT1/glyceraldehyde phosphate dehydrogenase: heart failure: 4.84 +/- 5.18;
      controls: 13.74 +/- 7.77; P < 0.005). Standardization of PCR resulting in a low
      coefficient of variance, high reproducibility, and large sample capacity is
      possible using optimal internal standardization and the liquid-phase
      hybridization/ELISA system for detection. The optimized PCR procedure indicated
      downregulation of atrial AT1 in end-stage human heart failure, suggesting a
      reduced capacity of the atria to respond to angiotensin II stimulation in end
      stage heart failure.

PMID- 8872859
TI  - Adenoviral-mediated delivery of herpes simplex virus thymidine kinase results in
      tumor reduction and prolonged survival in a SCID mouse model of human ovarian
      carcinoma.
AB  - The herpes simplex virus thymidine kinase gene is the most widely utilized toxin
      for selective killing of carcinoma cells. Expression of the viral thymidine
      kinase gene renders cells sensitive to the toxic effects of nucleoside analogs
      such as ganciclovir. An advantage of this system is the "bystander effect"
      whereby thymidine kinase transduced tumor cells elicit a toxic effect on
      surrounding nontransduced tumor cells. Ovarian carcinoma appears to be an ideal
      candidate for gene therapy as the majority of women present with advanced stage
      disease, have poor prognosis for long-term survival and have the disease confined
      within the peritoneal cavity. Therefore the utility of an adenoviral vector to
      elicit an in vitro bystander effect in ovarian carcinoma cells and the
      therapeutic efficacy of such a system in vivo was undertaken. Immunocompetent
      animals were utilized to determine the maximum dose of adenovirus that could be
      administered without any undesirable side effects and that preimmunization had no
      effects on subsequent challenge. SCID mice were orthotopically transplanted with
      human ovarian carcinoma cells and, after establishment of tumor, given a
      recombinant adenovirus expressing either the herpes simplex virus thymidine
      kinase or the Escherichia coli beta-galactosidase gene. Half the animals from
      each viral group were treated with either a ganciclovir regiment (50 mg/kg daily
      for 14 days) or an equal volume of serum-free media. A subset of mice were killed
      following drug treatment and analyzed for tumor reduction. The remaining animals
      were followed daily for survival. The animals treated with the recombinant
      adenovirus expressing the herpes simplex virus thymidine kinase gene and
      ganciclovir had significant reduction in overall tumor burden and demonstrated
      statistically significant prolongation in overall survival.

PMID- 8872860
TI  - Analysis of autoantibodies to plasminogen in the serum of patients with
      rheumatoid arthritis.
AB  - Sera from patients with rheumatoid arthritis containing high titers of anti
      streptokinase antibodies were found to contain anti-plasminogen antibodies of the
      IgG and IgA classes. High titers of anti-plasminogen autoantibodies of the IgA
      class were also found in sera from patients with systemic lupus erythematosus and
      Sjogren syndrome. Studies of the immune response to thrombolytic therapy with
      streptokinase in patients with no prior history of autoimmune disease suggest a
      strong correlation between streptokinase administration and the appearance of
      autoantibodies to plasminogen of the IgA class. The IgA anti-plasminogen
      autoantibody is specific for an epitope in a region of plasminogen which binds
      streptokinase and the IgG autoantibody reacts with an epitope in the C-terminal
      region corresponding to the catalytic domain of the plasminogen zymogen. Our
      findings suggest a different origin for the two classes of anti-plasminogen
      immunoglobulins in rheumatoid arthritis patients. Since plasminogen binding to
      rheumatoid synovial fibroblasts is enhanced, the high titers of both classes of
      anti-plasminogen autoantibodies may add to the localization and perpetuation of
      the immune response. We suggest that plasminogen may be a target of the immune
      response in autoimmune disease.

PMID- 8872862
TI  - Clinical pharmacology and clinical trials in Japan.
AB  - Clinical pharmacology is the pursuit of rational therapeutics by following the
      scientific principles of medicine and pharmacology. In Japan the roles for
      clinical pharmacology and clinical pharmacologists have been evolving since the
      discipline appeared in the 1950s. Clinical pharmacology and clinical trials for
      drug development depend on each other, and clinical pharmacologists play an
      important role in drug development in Japan. As the discipline becomes more
      important and complicated, many issues regarding drug therapeutics and clinical
      trials in Japan have been raised, and several points of view have been expressed.
      The following suggestions have been made to improve clinical pharmacology in
      Japan: (a) Medical education in the field of clinical pharmacology must be
      improved by creating or improving clinical pharmacology programs in medical
      schools. (b) The appropriate infrastructure for clinical trials must be
      established so that the physicians' workload is reduced, and patients'
      participation in clinical trials becomes much easier. (c) Scientific and ethical
      standards of the pharmaceutical industry must be improved, and the effort should
      be made to produce drugs with new mechanisms of action or with significant
      expected benefits. (d) The regulatory agency must provide stronger support,
      encompassing all the various points of view of academic institutes and the
      pharmaceutical industry. In light of the enthusiasm demonstrated by the
      government, physicians, and pharmaceutical industry in Japan for continued
      progress in clinical pharmacology, it seems likely that all its challenges will
      be overcome in the near future. Hence, despite the various problems discussed
      here the future seems promising for the continued development of clinical
      pharmacology.

PMID- 8872861
TI  - High frequencies of human T-lymphotropic virus type I (HTLV-I) infection and
      presence of HTLV-II proviral DNA in blood donors with anti-thyroid antibodies.
AB  - To investigate the relationship between human T-lymphotropic virus (HTLV) types I
      and II and the pathogenesis of autoimmune thyroid diseases, we examined serum
      anti-thyroid antibodies in 1019 blood donors with or without serum anti-HTLV-I
      antibody as well as proviral DNA for HTLV-II in leukocyte DNA by the polymerase
      chain reaction in 395 blood donors with or without anti-thyroid antibodies. The
      frequency of donors with anti-HTLV-I antibody who also showed anti-thyroid
      antibodies (7.9%) tended to be higher than that (6.3%) among donors who did not
      have the anti-HTLV-I antibody. The frequency of anti-thyroid antibodies in 125
      young male donors aged 16-39 years with anti-HTLV-I antibody (4.8%) was
      significantly higher (P < 0.05) than that (0.6%) in 164 control donors without
      the antibody. In blood donors with anti-thyroid antibody, 25.0% of those with
      anti-HTLV-I antibody and 14.3% of those without the antibody had HTLV-II proviral
      DNA. In contrast, in donors without anti-thyroid antibody HTLV-II proviral DNA
      was detected in 2.3% of those with anti-HTLV-I antibody and in 0.6% of those
      without the antibody. Thus the detection rates in donors with anti-thyroid
      antibody were significantly higher (P < 0.001) than those in donors without the
      antibody, regardless of HTLV-I infection. These results suggest that HTLV-I
      infection and the presence of HTLV-II proviral DNA may be independently related
      to the pathogenesis of autoimmune thyroid diseases.

PMID- 8872863
TI  - Adaptive changes in the rat dopaminergic transmission following repeated lithium
      administration.
AB  - In the present study the alterations in the contents of dopamine (DA) and
      metabolites, as well as in the levels of mRNA coding for DA receptor D2, were
      determined in the rat striatum (STR) and nucleus accumbens septi (NAS), in
      correlation with the duration of lithium administration. Single or subchronic (3
      days) administration of lithium produced less consistent effects as far as the
      levels of DA and metabolites are concerned; however, following 7 or 14 days of
      lithium administration, the DA release from terminals was significantly
      attenuated and the effect was more pronounced in NAS. After the same time of
      treatment, the increase in the levels of mRNA coding for the D2 receptor was
      increased; this might be interpreted as an adaptive change to the decreased
      dopaminergic transmission following the prolonged administration of lithium.

PMID- 8872865
TI  - Ultrastructural distribution of NADPH-diaphorase in the normal hippocampus and
      after long-term potentiation.
AB  - The distribution of the enzyme nitric oxide synthase (NOS) was investigated at
      the ultrastructural level in synaptic structures of the hippocampal formation in
      relation to long-term potentiation (LTP), based on the histochemical NADPH
      diaphorase (NADPH-d) staining with the tetrazolium salt BSPT. BSPT-formazan, the
      osmiophilic reaction product, was found to be selectively distributed and
      predominantly attached to membranes of the endoplasmic reticulum. In synaptic
      regions mainly the presynaptic sides showed labeling. Although several groups
      have demonstrated a principal involvement of NO in the LTP-mechanism, we found
      only a low, statistically insignificant increase in NADPH-d stained presynaptic
      areas of the dentate gyrus, where LTP was evoked. Postsynaptic elements also did
      not show any noticeable differences. Based on the present results, the
      predominantly presynaptic localization of NOS should be preferably considered in
      models describing a functional role of NO in LTP formation, despite the fact that
      we failed to reveal any indications for an LTP-related change in synaptically
      located NADPH-d.

PMID- 8872866
TI  - Influence of nicardipine, nimodipine and flunarizine on the anticonvulsant
      efficacy of antiepileptics against pentylenetetrazol in mice.
AB  - Among three calcium channel inhibitors, only nicardipine (10-40 mg/kg)
      significantly inhibited clonic seizures induced by pentylenetetrazol administered
      at its CD97 (convulsive dose 97%) of 81 mg/kg, subcutaneously. Nimodipine and
      flunarizine (both up to 80 mg/kg) did not suppress pentylenetetrazol-induced
      clonic seizures per se. Co-administration of nicardipine (5 mg/kg) resulted in a
      significant enhancement of the protective potency of either ethosuximide (50
      mg/kg) or valproate (100 mg/kg) against clonic seizures in this test. Similar
      effects were noted in case of combined treatment of nimodipine (20-40 mg/kg) with
      these antiepileptics. On the contrary, flunarizine (up to 20 mg/kg) did not
      modify the anticonvulsive action of these antiepileptic drugs. Moreover, none of
      the studied calcium channel inhibitors influenced the protective activity of
      clonazepam (0.01 mg/kg). The antiepileptic drugs, administered alone in above
      doses, were ineffective against pentylenetetrazol-induced clonic convulsions. In
      case of ethosuximide and valproate, the motor performance in the chimney test was
      worsened by co-administration of nimodipine (40 mg/kg). We found no
      pharmacokinetic interactions (at least in relation to the plasma levels of
      ethosuximide and valproate) that could explain the observed results. Thus, we
      conclude that a combination of some calcium channel inhibitors and antiepileptic
      drugs may provide more efficient protection against experimental seizures which
      may bear a potential clinical significance.

PMID- 8872864
TI  - Effects of chronic neuroleptic treatment on dopamine release: insights from
      studies using 3-methoxytyramine.
AB  - Antipsychotic medications appear to exert their therapeutic effects by blocking
      D2 receptors. While D2 blockade occurs rapidly, reduction in psychotic symptoms
      is often delayed. This time discrepancy has been attributed to the relatively
      slow development of depolarization inactivation (DI) of dopaminergic neurons. The
      reduced firing rates associated with DI has been hypothesized to reduce dopamine
      release and thus psychotic symptoms. Studies assessing changes in dopamine
      release during chronic neuroleptic treatment, using microdialysis and
      voltammetry, have been inconsistent. This may be due to methodological
      differences between studies, the invasive nature of these procedures, or other
      confounds. To investigate the effects of DI on dopamine release, 3-MT
      accumulation, an index of dopamine release that does not involve disruption of
      brain tissue, was measured during acute and chronic neuroleptic treatment. These
      results are compared with those using other techniques. 3-MT levels remained
      elevated after chronic treatment, suggesting that DI does not markedly reduce
      release. Regulation of dopamine release during DI was examined using two
      techniques known to block dopamine neuronal impulse flow. 3-MT levels were
      markedly reduced by both, implying that DI does not alter the portion of dopamine
      release mediated by neuronal impulse flow. Overall, studies to date suggest that
      the delayed therapeutic effects of neuroleptics are not due to reductions in
      impulse dependent dopamine release. Recent studies using a neurodevelopmental
      animal model of schizophrenia have pointed to altered pre- and post-synaptic
      indices of dopamine neurotransmission. The results suggest that neuroleptics may
      exert their therapeutic effects, in part, by limiting the fluctuations in
      dopamine release, and raise new issues for future research.

PMID- 8872867
TI  - Pineal response after pyridoxine test in children.
AB  - To characterize the pineal response to pyridoxine, plasma melatonin was measured
      in one hundred and twenty children 3 hours after vitamin B6 administration. The
      children, aged between 1.5 and 8 years, were divided in four groups as follows:
      a) control day group, grouping 27 children sampled at 9:00 and at 12:00; b)
      control night group, grouping 29 children sampled at 21:00 and at 24:00; c)
      pyridoxine day group, grouping 30 children sampled at 9:00, then intravenously
      (i.v.) injected with 3 mg/kg of pyridoxine, and sampled at 12:00; and d)
      pyridoxine night group, grouping 34 children sampled at 21:00, i.v. injected with
      3 mg/kg of pyridoxine, and sampled at 24:00. Melatonin concentration was measured
      by radioimmuno assay. The data obtained showed a significant increase in
      melatonin levels after pyridoxine administration in the pyridoxine night group
      (39.87 +/- 8.02 pg/ml basal vs 88.45 +/- 9.21 pg/ml after pyridoxine, p < 0.001).
      The other groups did not showed significant differences in melatonin
      concentrations. Statistical analysis shows that the administration of pyridoxine
      during the nocturnal hours represents a stimulating factor to increase the pineal
      production of melatonin in children.

PMID- 8872868
TI  - Genetic association between cytochrome P450IA1 gene and susceptibility to
      Parkinson's disease.
AB  - Idiopathic Parkinson's disease (PD) is a multifactorial neuro-degenerative
      disorder resulting from environmental factors acting on genetically susceptible
      individuals with normal aging. Cytochrome P450IA1 is a dioxin-inducible enzyme
      which is responsible for the activation of procarcinogens and environmental
      pollutants, such as benzo[alpha]pyrene and other aromatic hydrocarbons. The
      frequencies of polymorphic alleles of cytochrome P450IA1 gene (CYPIA1) were
      studied in 126 unrelated patients with PD in comparison with 176 healthy
      Japanese. The frequency of the Msp I polymorphic allele, a variant of CYPIA1
      (m2), was significantly higher in patients with PD (0.444) than in controls
      (0.349). The risk of PD in homozygotes for m2 was 2.34-fold greater than
      homozygotes for the wild-type, m1. The relative risk for PD in homozygotes for
      CYPIA1Val was 6.54-fold higher than in homozygotes for the wild type
      (CYPIA1Ile)(p < 0.001). These results strongly suggest that the CYPIA1 might be
      one of the susceptibility genes for PD.

PMID- 8872869
TI  - Cholecystokinin peptides and receptor binding in Alzheimer's disease.
AB  - Cholecystokinin (CCK) is a peptide that can be found in the cerebral cortex in
      high concentrations and is involved in learning and memory as well as
      neurodegenerative processes. Cortical brain samples from 9 patients with
      Alzheimer's disease and 9 matched control cases were studied with respect to the
      concentrations of various molecular forms of CCK and the CCK receptor binding
      characteristics. No differences were found between patients and controls in any
      of these measures. Significant correlations were found between the concentrations
      of CCK-8 sulphated and the three nonsulphated CCK peptides measured. In addition,
      the concentrations of CCK-4 and CCK-5 showed a highly significant and positive
      correlation.

PMID- 8872870
TI  - Influence of vitamin B12 on brain methionine adenosyltransferase activity in
      senile dementia of the Alzheimer's type.
AB  - The influence of vitamin B12 on the activity of methionine adenosyltransferase
      (MAT) in postmortem brains of patients with senile dementia of the Alzheimer's
      type (SDAT) was investigated. In samples of cortex gyrus frontalis from SDAT
      patients with normal and low levels of serum B12, MAT Vmax was significantly
      increased by 25% and 19%, respectively. MAT Vmax from a SDAT group chronically
      treated with B12 was similar to controls. In contrast to cortex gyrus frontalis,
      no significant alterations were seen in MAT activity in nucleus caudatus. This
      study provides evidence that SDAT is associated with significant alterations in
      transmethylation mechanisms in specific regions of the brain. The relationship
      between blood levels of B12 and the actual status of this vitamin in the brain
      influencing the rates of synthesis of both methionine and SAM may, however, be
      far more complex and cannot be directly clarified on the basis of the present
      human brain results.

PMID- 8872871
TI  - Cognitive effects of scopolamine in dementia.
AB  - Cholinergic deficiency was postulated to play an important role in the mental
      decline observed in Alzheimer's (AD), Parkinson's (PD) and multiinfarct (MID)
      dementia. In the present study, 11 AD, 8 MID and 7 PD patients (DSM III-R
      diagnostic criteria for dementia) and 9 healthy age-matched controls (CTRL) were
      given IV 0.5 mg scopolamine (SCO) or placebo (PLA) in random order (double blind)
      within one week. The Hebrew Short Mental Test (SMT) and Wechsler Memory Scale
      (WMS) were administered before and after SCO and PLA in each patient. A
      comparison of SCO vs. PLA utilizing MANCOVA (the covariate being the basal mental
      performance [BAS] with SMT or WMS) showed that SCO affected all the groups
      similarly, except for the Wechsler subtest of logic memory which showed larger
      deterioration in CTRL compared to demented patients. ANOVA and MANCOVA analyses
      did not distinguish between the three demented groups. SCO administration does
      not differentiate between demented patients and CTRL and does not enable
      discrimination between patients with AD, MID and PD. Moreover, some CTRL with
      still normal cognitive performance, but lower BAS may be more vulnerable to SCO
      than others. The integrity of the cholinergic system may be responsible for the
      different sensitivity to SCO challenge.

PMID- 8872872
TI  - T-maze and food reinforcement: an inexpensive drug discrimination procedure.
AB  - The present study provides a detailed description of a novel drug discrimination
      procedure employing a T-maze and food reinforcement. Three groups of rats (n = 5)
      were trained to run one of the two arms of the maze after the i.g. administration
      of either 1.0, 1.5 or 2.0 g/kg ethanol (chosen as training drug) and the opposite
      arm after administration of water. Only correct trials were rewarded. All the
      rats learned the discrimination task. Substitution tests with different doses of
      ethanol in all the three groups and with the non-competitive NMDA antagonist,
      dizocilpine (MK-801), in the 2.0 g/kg ethanol-trained group provided a
      pharmacological validation of the paradigm. Advantages and disadvantages of this
      procedure are discussed.

PMID- 8872873
TI  - Triple immunofluorescence labelling of parvalbumin, calbindin-D28k and calretinin
      in rat and monkey brain.
AB  - This study presents novel techniques for the concomitant cytochemical detection
      of the calcium-binding proteins parvalbumin, calbindin-D28k and calretinin which
      are frequently used neuronal markers. For the triple immunofluorescence labelling
      of such antigens in rat and monkey brain--with emphasis on the cortex--we
      developed four different protocols which revealed obviously identical
      distribution patterns in consecutive sections. These methods included the
      simultaneous use of purified monoclonal antibodies directed against parvalbumin
      and calbindin--D28k--haptenized with biotin or digoxigenin--and subsequent
      visualization with fluorochromated hapten-recognizing immunoreagents. For the
      combined visualization of the calcium-binding proteins we applied the bright red
      fluorescent carbocyanine Cy3, blue fluorescent 7-amino-4-methylcoumarin-3-acetic
      acid (AMCA) and as green fluorophore either fluorescein or the newly introduced
      carbocyanine Cy2. The latter showed a higher fluorescence intensity and more
      resistance against photobleaching than fluorescein. In addition to clearly
      distinguished distribution patterns of the calcium-binding proteins, neurons co
      expressing parvalbumin and calbindin-D28k in the parietal and piriform cortex of
      rat were demonstrated. The elaborated methods might stimulate the further
      detailed investigation of spatial and functional relationships between structures
      immunopositive for selected neuroanatomical markers.

PMID- 8872874
TI  - Continuous enzyme-linked fluorometric detection of L-(+)-lactate released from
      rat brain vesicles under anoxic conditions.
AB  - A method is described for the on-line detection of L-(+)-lactate released from
      brain vesicles under physiological conditions. The principle of L-lactate
      detection is based on the reversible oxidation of L-lactate catalysed by L
      lactate dehydrogenase (LDH, EC 1.1.1.27) employing 3-acetylpyridine-adenine
      dinucleotide (APAD) as analogue of NAD according to the reaction: L-lactate +
      APAD reversible pyruvate + APADH. In practical terms, L-lactate synthesis of
      vesicles incubated in the presence of LDH and APAD was continuously followed by
      the fluorescence (490 nm) of APADH excited at 410 nm. Addition of a L-lactate
      standard (10 mumol/l) enhanced APADH fluorescence with a half-life of 6.0 +/- 0.6
      s allowing us to uncover a short-term alteration of L-lactate synthesis. This
      method was applied to evaluate a prospective change of L-lactate generation
      caused by the anoxia-induced increase in intravesicular Na+ and Ca2+
      concentration ([Na+]i, [Ca2+]i), both fluorometrically determined by SBFI and
      Fura, respectively. Upon anoxia, [Na+]i and [Ca2+]i increased continuously up to
      40 mmol/l Na+ and 900 nmol/l Ca2+ within 400 s. Concurrently, intravesicular NADH
      ([NADH]i) and basal L-lactate synthesis were enhanced within a few seconds, the
      latter from 4.2 +/- 1.5 to 15.8 +/- 1.5 nmol L-lactate/min per mg protein.
      Incubation of vesicles in the presence of 10 mumol/l tetrodotoxin (TTX)
      suppressed the increase in [Na+]i and [Ca2+]i but failed to influence L-lactate
      synthesis. The data indicate a continuous Na+ influx via voltage-dependent Na+
      channels accompanied by an increase in [Ca2+]i during anoxia which did not affect
      anaerobic L-lactate synthesis. The method of fluorometric L-lactate determination
      was confirmed to be suitable for the detection of L-lactate released under
      physiological conditions from brain vesicles and seems to be applicable to
      various cell models.

PMID- 8872875
TI  - The potential of high-resolution positron emission tomography to monitor striatal
      dopaminergic function in rat models of disease.
AB  - The use of a recently commissioned small-diameter, high-resolution positron
      emission tomography (PET) to obtain a measure of specific binding of 3 carbon-11
      labelled ligands in rat striatum is described. Using cerebellum as a reference
      tissue, compartmental modelling was used to obtain individual estimates of
      striatal binding potential (defined as the ratio of rate constants to and from
      the specifically bound compartment) for [11C]raclopride (D2 receptors), [11C]SCH
      23390 (D1 receptors) and [11C]RTI-121 (dopamine transporter). The coefficients of
      variation in control, anaesthetized rats were of the order of 10%. Using two
      models of human disease, namely striatal injection of ibotenic acid to produce
      postsynaptic cell loss as in Huntington's disease, and 6-hydroxydopamine
      injection into substantia nigra pars compacta to mimic dopaminergic terminal loss
      in Parkinson's disease, marked reductions in binding potential were observed for
      the corresponding pre- or postsynaptic markers. When the regions of interest are
      so small as to be of the order of the spatial resolution of the system, factor
      such as spill over and partial volume negate absolute quantification of tissue
      radioactivity. Nevertheless, the use of PET to monitor relative changes in
      dopaminergic integrity should be considered as a viable complement to established
      in vivo microdialysis and post mortem techniques.

PMID- 8872876
TI  - Microperfusion of picrotoxin in the hippocampus of chronic freely moving rats
      through microdialysis probes: a new method of induce partial and secondary
      generalized seizures.
AB  - In this study we investigated the threshold and latency of seizures in a new
      model of chemically induced partial seizures, with or without secondary
      generalization. We performed repeated experiments with a maximum of 20 between
      day seizures on each individual rat over a period up to 6 months, with resting
      intervals ranging from 3 to 15 days depending on the severity of seizures.
      Seizures were induced by microperfusion of variable doses of picrotoxin starting
      at 100 microM in each animal and increasing in steps of 25 microM through
      microdialysis probes introduced in the hippocampus of freely moving rats. The
      seizures were registered in a Holter-EEG and videotaped. Only one picrotoxin dose
      was perfused during each experimental session. Threshold was defined as the
      minimum dose of picrotoxin which induced a type of seizure after a 5 min period
      of perfusion. Latency was defined as the period from the end of the
      microperfusion period to the onset of electro-behavioral seizures. Patterns of
      seizures induced in different experimental sessions showed a dose-dependent
      variation ranging from arrest behavior (absence-like) to rapidly recurring
      seizures. A permanent seizure threshold for each type of seizure was observed in
      repeated experiments within individual rats, but when compared with different
      animals, significant variations in threshold were observed. A long latency period
      (14-41 min) was observed, unrelated to threshold or seizure type. Since the
      method can induce separate seizures with constant seizure threshold in experiment
      rats over a testing period as long as 6 months, the described method offers a new
      way to test a large number of antiepileptic drugs on the same animals.

PMID- 8872877
TI  - Voltage-clamp analysis of neurons within deep layers of the brain.
AB  - Single electrode whole cell current- and voltage-clamp techniques in conjunction
      with intra- and extracellular phoresis and extracellular application of
      pharmacological agents were applied to study neurons in deep layers of the
      brainstem of anesthetized, paralyzed and artificially ventilated cats. We
      compared slow rhythmic changes and stimulus-evoked postsynaptic current and
      voltage responses of neurons as they were recorded with fine-tipped
      microelectrodes filled with 2-3 M 'microelectrode solutions' or with 0.3 M 'patch
      solutions', or with patch electrodes. The experimental data were then compared
      with the effects of somatic and dendritic conductance changes simulated in a cell
      model. A new method was introduced for alternating current and voltage-clamp
      measurements performed at 300 Hz, which provided quasi-simultaneous measurements
      of slow changes of spontaneous synaptic currents and potentials. During current
      or voltage clamp, chemicals which affect voltage- and receptor-controlled
      conductances were ionophoresed intracellularly through single or theta-type glass
      electrodes. We show examples of activation of low-voltage activated Ca2+
      responses after blockade of Na+ currents by intracellular QX 314 and K+ currents
      by intracellular Cs+ injections in addition to Sp-cAMPs to activate protein
      kinase A. TEA, NMDA and GABA were used to demonstrate the effectiveness of
      extracellular application of drugs through multibarrel electrodes or local
      application through a 'bath'. The various tests demonstrated that single
      electrode whole cell current- and voltage-clamp methods, in combination with
      various techniques for drug application, can be well applied to study the
      biophysical properties and pharmacological sensitivities of neurons embedded in
      in vivo networks within deep layers of the brain.

PMID- 8872878
TI  - 'Real time' measurement of dopamine release in an in vitro model of neostriatal
      ischaemia.
AB  - Dopamine (DA) is released in large quantities during ischaemia and may be
      neurotoxic. For instance, reduction of DA release is associated with a better
      histological outcome following experimental stroke. In the present study, we
      report the measurement of transmitter release in an in vitro model of cerebral
      ischaemia using brain slices. Striatal slices were subjected to 'ischaemia' by
      reducing the O2 and glucose content of the superfusate in a controlled fashion.
      The resultant monoamine release, measured in real time by fast cyclic voltammetry
      at carbon fibre microelectrodes, was shown to be DA by electrochemical criteria.
      Upon imposition of an ischaemic episode, there was a lag period (159 +/- 2 s,
      mean +/- S.E.M., n = 99) followed by a sudden release of DA, reaching a maximum
      extracellular concentration of 95 +/- 4 microM in 25 +/- 2 s. This overall
      profile of DA release was qualitatively similar to that measured in the striatum
      in vivo following cardiac arrest. The DA uptake inhibitor GBR 12935 (1.0 microM)
      had no effect on any DA release variable. We conclude that this model mimics many
      of the features of cerebral ischaemia in vivo and may be a suitable vehicle for
      the investigation of neuroprotective drugs.

PMID- 8872879
TI  - Analysis of neural bursting: nonrhythmic and rhythmic activity in isolated spinal
      cord.
AB  - Neuronal firing recorded from primary afferents and central spinal neurons in
      isolated mammalian spinal cord in vitro was analyzed using interspike interval
      histograms and Poincare maps (Return maps). Interspike interval histograms
      described the time between two successive spikes. However, Poincare maps
      represented the interspike interval preceding a spike against the interspike
      interval following the spike. The variability in firing of neurons occurring
      naturally in different preparations was explored. In a presumptive single central
      spinal neuron, the firing pattern provided a single cluster. During bursting in a
      presumptive single primary afferent, the Poincare maps provided information on
      interburst intervals. Moreover, lengthening and or shortening of interspike
      intervals within bursts can be detected in the maps. The firing of a population
      of neurons was modulated using a pharmacological intervention with 4
      aminopyridine and resulted in a complex Poincare map.

PMID- 8872880
TI  - Dextran backfill tracers combined with Lucifer yellow injections for
      neuroanatomic studies of the leech head ganglion.
AB  - Several neuronal tracing substances were applied to the cut ends of leech
      cephalic nerves and the resulting backfills into the subesophageal ganglion
      (sbEG) were mapped. A 12 h incubation in 3 kDa dextrans conjugated either to a
      fluorochrome or to biotin (subsequently tagged with peroxidase) was satisfactory.
      In separate experiments, possible targets of cephalic nerve afferents (R3 Retzius
      neurons) were injected with Lucifer Yellow (LY) to visualize their projections.
      Comparison of the LY-R3 Retzius neuron map with that of the dextran-backfilled D1
      nerve revealed extensive overlap in the sbEG. Experiments were performed
      combining the two protocols, confirming this observation. Moreover, confocal
      microscopy placed D1 nerve processes in close proximity to R3 Retzius neuron
      processes, suggesting that they could make synaptic contact with one another in
      the sbEG. With modifications, this method could be used to identify such contacts
      using electron microscopy.

PMID- 8872881
TI  - In situ visualization and photoablation of individual neurons using a low cost
      fiber optic based system.
AB  - This paper describes a low-cost system for in situ visualization and
      photoablation of single neurons. The system includes a fiber optics light source
      equipped with a filter port, a blue excitation filter and a yellow barrier
      filter, and a light guide which terminates with a focusing lens. This system is
      inexpensive, easy to use, and requires minimal maintenance. Given its price, this
      system is readily accessible and has the potential of becoming standard equipment
      for in situ visualization and killing of individual neurons.

PMID- 8872882
TI  - Epigenetic factors controlling the development of avian Purkinje neurons.
AB  - Using a unique protocol, we have developed an avian neuron culture system in
      which a high yield of Purkinje neurons is obtained more readily than with pre
      existing methods. Purkinje neurons were identified in vitro using the specific
      antibodies calbindin and cyclic GMP-kinase. Survival of Purkinje neurons was
      dependent on astrocyte contact and enhanced by astrocytic factors supplied to the
      medium by a monolayer of astrocytes grown on coated membranes suspended in the
      culture wells but not in contact with the neurons. The age of the cerebellum from
      which astrocytes were obtained was shown to affect the morphological development
      of the Purkinje neurons suggesting the developmentally-regulated expression of
      growth factors. However, in the presence of the astrocytes, Purkinje neurons
      could only progress to a limited stage of development based on morphological
      criteria. The addition to the culture of cerebellar granule neurons at a time of
      Purkinje neuron development that they would expect to encounter them in vivo
      resulted in a shift of Purkinje neurons to a mature phenotype. This maturation
      effect was increased in response to increasing levels of granule neurons, but was
      independent of the granule neuron ages used. This system offers significant
      advantages over other Purkinje neuron culture systems and will be useful for
      studying the extrinsic factors involved in Purkinje neuron development and
      histogenesis.

PMID- 8872883
TI  - A linear method for the curve fitting of multiexponentials.
AB  - Two single-pass methods for fitting multiexponentials to experimental data are
      described. These methods rely on the construction of a matrix whose
      characteristic polynomial is used to determine the rates of decay. In the first
      method, which we call the multiple-delay method, the matrix is constructed using
      time delays of the experimental data. This method is fast and highly accurate
      even if the experimental signal contains exponential components with similar
      rates of decay. In the second method, which we call the successive-integral
      method, the matrix is constructed using integrals of the experimental data. This
      procedure yields good results for noisy signals and is a generalization of the
      method of Martin et al. ((1993) J. Neurosci. Methods, 51: 135-146). In addition,
      a particular instability of the multiexponential curve fitting problem is
      identified and a method for overcoming this instability is given.

PMID- 8872884
TI  - An automated system for regulating brain temperature in awake and freely moving
      rodents.
AB  - In rodents, postischemic hypothermia can provide robust and long-term functional
      and histological neuroprotection, even when intervention is delayed for several
      hours following ischemia. This generates a need to follow temperature precisely
      for many hours, perhaps several days if a hypothermic effect is to be studied or
      excluded. Such protracted temperature control (> 24 h) is difficult and often
      lethal when performed under general anesthesia. In awake animals, manual
      temperature control is safer, but exceedingly time consuming and tedious, and is
      impractical for large experiments. The present method allows for continuous brain
      temperature measurement and control in free-moving rats and gerbils. Brain
      temperature was measured by wireless AM probes while feedback regulation was
      achieved by servo-control of a lamp, fan and water misting system. Hypothermia
      was easily induced and maintained for 24 h at 32 degrees C in both gerbils and
      rats. Gerbils also tolerated 24 h at 32 degrees C followed by 24 h at 34 degrees
      C. This 'exposure technique' is capable of safely producing lengthy periods of
      mild hypothermia in rats and gerbils. Furthermore, this method can clamp
      temperature when temperature-altering drugs are given. For example, temperature
      was maintained in MK-801 drugged gerbils. The system is, therefore, eminently
      suitable for drug neuroprotection studies in brain ischemia.

PMID- 8872885
TI  - A method for automatic identification of saccades from eye movement recordings.
AB  - We describe a technique for reliable and rapid automatic identification of
      saccades in eye movement records. The signal processing that we describe will be
      useful to anyone wanting to analyse large numbers (thousands) of eye movements.
      We describe a transform that is derived from the differentiated eye movement
      record, and which is related to a transform previously used to automate analysis
      of EMG recordings.

PMID- 8872886
TI  - Antibody-coated electrodes for detecting somatic exocytosis of somatostatin-like
      material in Helix neurones.
AB  - Immunoelectrodes have been developed which can be used to detect minute amounts
      of somatostatin. They were made with electrochemically treated glassy carbon
      fibres coated with anti-somatostatin antibodies. Calibration and various controls
      were carried out to ensure that the immunoelectrodes responded specifically to
      the presence of femtomolar somatostatin. Electrophysiological experiments were
      performed on anti-somatostatin immunoreactive neurones in the snails Helix
      aspersa and H. pomatia. Somatostatin-like material was released in response to
      sustained firing. The release was measured at the soma, which means that it
      occurred in the extrasynaptic area. The finding that the fluorescent dye FM 1-43
      was incorporated into somatic vesicles confirmed that exocytosis actually
      occurred during sustained neuronal firing.

PMID- 8872887
TI  - A magnetic field system using implanted sensors to track limb movements in the
      monkey.
AB  - This paper describes the design and construction of a magnetic field system with
      implanted sensors, capable of tracking limb orientation during unconstrained
      movements of awake, behaving monkeys. Tiny sensors (approximately 5 mm diameter)
      made from two orthogonal coils of wire are implanted in the monkey's upper arm,
      forearm, and hand. Three mutually orthogonal magnetic fields are detected by each
      sensor, providing sufficient information to determine the orientation of each
      limb segment. The use of implanted sensors and magnetic fields overcomes the two
      main difficulties associated with the use of existing tracking systems with
      monkeys. (1) It is impossible for the monkey to interfere with the sensors. (2)
      The sensors are never obscured because the body is permeable to magnetic fields.
      The tracking system provides highly accurate yaw, pitch, and roll orientation
      information for each limb segment within a cubical workspace approximately 50 cm
      on a side. Noise is less than 0.3 degrees, and long-term drift is on the order of
      0.2 degrees/h. The system is insensitive even to large pieces of steel within the
      field, provided the sensors remain at least 10-15 cm from the metal.

PMID- 8872888
TI  - A baseline detection method for analyzing transient electrophysiological events.
AB  - A baseline detection method has been developed that identifies and defines event
      transitions for whole-cell voltage or current ('transient') events that are
      produced by the activity of ion channel ensembles. The method utilizes a variety
      of iterative techniques that independently determine, for each event, several
      output parameters that are ultimately referrable to the mean and variance of each
      pre-event baseline. Examination of miniature endplate potentials using the
      baseline detection method provided the following output parameters for each
      transient event: pre-event mean and variance; rise time; peak amplitude and
      duration; a determination of whether the decay phase was best fit by a one- or
      two-component negative exponential function; time constants for the slow and/or
      fast decay components; percent contribution of the slow component to the decay
      phase; and the predicted peak amplitude determined by extrapolation of the least
      squares fit to the decay phase. Joint probability density representations
      involving the rise time and peak amplitudes of miniature endplate potentials
      indicated the power of this multivariate approach in identifying and isolating
      specific event classes. The baseline detection method is particularly
      advantageous for analyzing records containing multiple classes of event
      amplitudes, and provides a reproducible statistical standard for the analyses of
      transient events that are characteristic of whole-cell electrophysiological
      recordings.

PMID- 8872889
TI  - Combining 'caged-dopamine' photolysis with fast-scan cyclic voltammetry to assess
      dopamine clearance and release autoinhibition in vitro.
AB  - We have developed a methodology for inducing a rapid rise in extracellular
      dopamine concentrations. The clearance of the applied dopamine, as well as its
      effect on the endogenous dopamine release (i.e., autoinhibition), was then
      examined using fast scan cyclic voltammetry. In a recording chamber mounted on a
      Nikon Optiphot epifluorescence microscope, coronal rat brain slices containing
      either the caudate nucleus or prefrontal cortex were perfused with ACSF
      containing 100-200 microM 'caged-DA.' UV illumination (100-200 ms) focused at the
      tip of the recording electrode produced a peak DA concentration of 1-2 microM
      within 100-200 ms of terminating the illumination. The caudate nucleus exhibited
      a faster clearance rate for photo-released DA compared to the prefrontal cortex.
      Cocaine reduced the clearance rates in both the caudate nucleus and prefrontal
      cortex. In the prefrontal cortex a combination of desipramine/clomipramine also
      reduced dopamine clearance, suggesting heterologous uptake of the applied DA by
      noradrenergic and/or serotonergic terminals. Photo-released dopamine inhibited
      release of endogenous caudate DA release evoked by single electrical stimulation.
      The advantages of this methodology are discussed.

PMID- 8872890
TI  - A portable chamber for long-distance transport of surviving human brain slice
      preparations.
AB  - Incubation chambers for surviving brain slice preparations are in most cases
      designed to be stationary. For investigations on human brain tissue resected for
      the treatment of brain tumor or epilepsy, portable incubation chambers are needed
      in addition to stationary ones to allow transport of the slices between
      laboratories and hospitals located far from each other. For such purposes,
      interface chambers have been in use. In view of the ongoing discussion of the
      merits of interface versus submerged baths, here we describe an alternative
      chamber as a lightweight, easy to assemble portable bath of the submersion type
      for transport of surviving brain slice preparations over considerable distances.
      The chamber has been used in a variety of investigations on human brain slices.
      These slice preparation showed bioelectric properties comparable to those
      reported in investigations by other laboratories using stationary incubation
      chambers in cases where portable ones were not needed.

PMID- 8872891
TI  - Spread of stimulating current in the cortical grey matter of rat visual cortex
      studied on a new in vitro slice preparation.
AB  - Extracellular electrical stimulation of the cortical grey matter is very often
      used in electrophysiological studies, but the parameters of the stimulation
      itself have received only little attention. This study addresses the issue of the
      spread of stimulating current in rat visual areas 17 and 18a maintained in vitro.
      The preparation of the slices relied on a protocol making use of several of the
      means known to limit the effects of ischaemia: Halothane anaesthesia was used
      during the surgery and intracardiac perfusion was employed to reduce the brain
      temperature, to increase the intracerebral concentration of glucose and magnesium
      and to decrease that of calcium. The spread of stimulating current has been
      determined from strength-distance relationships established for the activation of
      axons. The strength-distance curves could be fitted by a quadratic relationship,
      indicating that the threshold current for the activation of an axon increases as
      the square of the distance separating it from the tip of the stimulating
      electrode. The slope of the regression line between threshold intensity and
      squared distance (k coefficient) is highly variable from one axon to another
      (range 2100-27 500 microA/mm2, median 8850 microA/mm2). Part of this variability
      is related to differences in conduction velocity. The theoretical number of
      axonal branches and axon initial segments activated by a given current intensity
      has been extrapolated from these experimental results.

PMID- 8872892
TI  - Review: cytokines and the pathogenesis of multiple sclerosis.
AB  - Perivascular accumulation of mononuclear cells (MNCs) in the central nervous
      system (CNS) and high levels of myelin autoantigen-reactive T cells in blood and
      further enriched in cerebrospinal fluid (CSF) are characteristic for multiple
      sclerosis (MS) and suggest a role for immunoregulatory cytokines in MS
      pathogenesis. The difficulties inherent to measurements of cytokine
      concentrations in body fluids have been partly overcome by adopting techniques
      allowing cytokine determinations on cellular level. MS is associated with the
      parallel up-regulation of proinflammatory [interferon-gamma (IFN-gamma), tumor
      necrosis factor-alpha (TNF-alpha), lymphotoxin-alpha, and interleukin (IL)-12]
      and immune response-down-regulating [transforming growth factor-beta (TGF-beta),
      IL-10] cytokines systemically. A preferential up-modulation of TNF-alpha and
      lymphotoxin-alpha is observed in clinical exacerbations and of TGF-beta and IL-10
      in remissions. The B cell-stimulating IL-4 and IL-6 are also up-regulated in MS,
      as is the cytolysis-promoting perforin. Cytokine production is elevated to an
      even higher degree in the CSF than systemically, underlining the autonomy of the
      immune responses in the CSF. All cytokine abnormalities are demonstrable already
      in very early MS, manifested by acute unilateral optic neuritis associated with
      more than two MS-like lesions on brain magnetic resonance imaging and oligoclonal
      IgG bands in CSF. The cytokine abnormalities hitherto observed are not MS
      specific, because they can be found in other inflammatory CNS diseases, e.g.,
      aseptic meningitis and even noninflammatory neurological diseases like stroke.
      The influence on cytokine profiles, e.g., suppressing proinflammatory cytokines
      and promoting TGF-beta and IL-10, could be an important way to identify new and
      promising treatments of MS.

PMID- 8872893
TI  - Dysregulation of potentially pathogenic self reactivity is crucial for the
      manifestation of clinical autoimmunity.
AB  - During the evolution of the autoimmune response to myelin basic protein (MBP), at
      least two distinct lymphocyte populations arise, one that is specific for
      determinants within the protein antigen and another that is specific for the
      receptors displayed by the antigen-specific lymphocytes themselves. The T-cell
      receptor (TCR)-specific lymphocytes appear to oppose the action of the pathogenic
      effector cells, which predominantly utilize the TCR V beta 8.2 gene segment. We
      will discuss our work suggesting that both CD4 and CD8 cells specific for
      different TCR determinants on the V beta 8.2 chain are involved in the regulation
      of MBP-specific CD4 T cells mediating experimental autoimmune encephalomyelitis.
      We suggest that a crucial balance between the effectors and regulators is
      decisive for the clinical manifestation of autoimmunity.

PMID- 8872894
TI  - Hypothesis: a possible role for mast cells and their inflammatory mediators in
      the pathogenesis of autoimmune encephalomyelitis.
AB  - Mast cells and their potent chemical mediators are known to initiate and modulate
      a number of important inflammatory cascades. With respect to the central nervous
      system, the role of mast cells as participants in the promotion and resolution of
      inflammation has been widely underestimated. Mast cell-derived histamine,
      serotonin, kallikreins, and tumor necrosis factor-alpha (TNF-alpha) can enhance
      microvascular permeability, leukocyte rolling, adhesion, and extravasation of
      inflammatory cells into the brain and spinal cord. Mast cell mediators may play
      an important role in autoimmune encephalomyelitis and multiple sclerosis by
      promoting the entry of autoreactive T cells and the recruitment of nonspecific
      monocytes across the blood:brain barrier.

PMID- 8872895
TI  - Concept of autoimmunity following spinal cord injury: possible roles for T
      lymphocytes in the traumatized central nervous system.
AB  - The effect of immunological activation on the neuropathologic sequelae and
      neurologic outcome from spinal cord injury is unclear. Similar to models of
      neuroinflammatory disease (e.g., experimental autoimmune encephalomyelitis; EAE),
      injury to the spinal cord precipitates the activation of resident microglia and
      the recruitment of circulating inflammatory cells (e.g., macrophages and
      lymphocytes). In EAE, these cells are known to cause tissue damage and loss of
      neurological function via autoimmune reactions to myelin proteins. The role these
      cells play in the pathology of traumatic injury to the spinal cord has not been
      clarified. In this review, data are presented that indicate that T cells isolated
      from spinal-injured rats are capable of causing neurologic deficits and
      histopathologic changes similar to EAE when injected intravenously into naive
      animals. These data are consistent with the concept of trauma-induced autoimmune
      reactions. However, disease transfer was only possible when T cells were obtained
      from animals at 1 week post-injury. Thus, the encephalitogenic T-cell repertoire
      appears to be rapidly regulated. It is possible that trauma-induced autoimmunity
      evolves into a mechanism by which the autoreactive repertoire regulates ongoing
      central nervous system (CNS) immunologic responses. Similar immunoregulatory
      networks have been proposed in EAE and are discussed here in the context of CNS
      trauma and neurodegenerative disease.

PMID- 8872896
TI  - Effect of Theiler's murine encephalomyelitis virus and cytokines on cultured
      oligodendrocytes and astrocytes.
AB  - The pathogenesis of Theiler's murine encephalomyelitis virus (TMEV)-induced
      demyelinating disease is still controversial. Our hypothesis is that primary
      infection of oligodendrocytes (OLGs) is not a crucial event in the pathogenesis
      of demyelination in this model. In fact, it has been proposed that myelin may be
      destroyed, as an innocent bystander, following an antiviral delayed-type
      hypersensitivity (DTH) response. This hypothesis would not need widespread
      oligodendroglial infection, because virus present in other cells would be
      sufficient to trigger a DTH response. The present study demonstrates that
      cultured OLGs and astrocytes from susceptible strains of mice (SJL and DBA) and
      immortalized OLGs can be infected with TMEV in vitro. Infection of OLGs, however,
      is at very low levels and does not result in overt cytolytic effect. In contrast,
      infection of immortalized OLGs is very efficient and results in clear cytolysis.
      Because an important characteristic of DTH responses is the liberation of
      potentially injurious cytokines into adjacent tissues, we also examined the
      effects of mouse recombinant tumor necrosis factor-alpha (TNF-alpha), interleukin
      1 alpha (IL-1 alpha), and interferon-gamma (IFN-gamma) on cultured OLGs and
      immortalized OLGs. We found that TNF-alpha caused immortalized OLG cytotoxicity
      in a time- and dose-dependent manner. In contrast, no cytotoxicity was observed
      on primary OLGs with any of the above cytokines. To determine whether functional
      effects could be demonstrated on primary OLGs by either virus or cytokines, we
      measured mRNA expression of different myelin proteins in primary and immortalized
      OLGs exposed to virus or TNF-alpha. Neither the BeAn strain or the GDVII strain
      of TMEV interfered with myelin protein mRNA expression in primary OLGs, whereas
      GDVII virus dramatically reduced myelin OLG glycoprotein (MOG) mRNA in
      immortalized OLGs. Interestingly, although even high concentrations of TNF-alpha
      (10,000 U/ml) did not produce primary OLG cytotoxicity, they resulted in a
      significant reduction in mRNA for both myelin basic protein (MBP) and MOG in
      these cells. TNF-alpha (at 500 U/ml) also specifically reduced MOG mRNA in
      immortalized OLGs. Because immortalized OLGs are considered to be arrested at an
      early stage of maturation, our results suggest that immature OLGs are susceptible
      to both virus- and cytokine-dependent cytotoxicity, whereas mature OLGs are
      resistant to cytolysis by either TMEV or cytokines. TNF-alpha, however, is
      capable of reducing mRNA expression of myelin proteins in primary OLGs;
      therefore, it may participate in the induction of demyelination, as suggested by
      the DTH-mediated hypothesis.

PMID- 8872897
TI  - Regulation of CD14 expression on human adult central nervous system-derived
      microglia.
AB  - Microglial cells function as regulators of immune reactivity within the CNS and
      may contribute to tissue injury under inflammatory conditions. Such functions are
      correlated with their state of activation. In this study, we report the de novo
      expression of CD14 by adult human CNS-derived microglia which acquire a bipolar
      activated morphologic phenotype in dissociated tissue culture. Surface CD14
      expression can be down-regulated by interaction with its ligand
      lipopolysaccharide (LPS), and by the T-helper (Th1) cytokine interferon-gamma
      (IFN-gamma) or the Th2 cytokine interleukin-4 (IL-4). Semiquantitative polymerase
      chain reaction (PCR) analysis of CD14 mRNA expression under each condition
      suggests a different mechanism accounting for the reduced surface expression. LPS
      down-regulates CD14 mRNA, consistent with a feed-back signal preventing over
      stimulation. IFN-gamma augments CD14 transcription, suggesting cleavage of
      surface CD14 consequent to general cell activation. IL-4 decreases mRNA
      production likely reflecting a generalized suppressive effect. The effect of LPS,
      IFN-gamma and IL-4 on CD14 expression differes from their effect on expression of
      the immune-accessory molecules B7-1 and HLA-DR, and on production of tumor
      necrosis factor-alpha (TNF-alpha), whose secretory pathway is similar to that of
      CD14. These results indicate the selective effects of molecules, likely to be
      present in the infected or inflamed CNS, on regulating CD14 expression and that
      there can be differential regulation of immune response relevant molecules
      expressed by activated microglia.

PMID- 8872898
TI  - Mouse astrocytes respond to the chemokines MCP-1 and KC, but reverse
      transcriptase-polymerase chain reaction does not detect mRNA for the KC or new
      MCP-1 receptor.
AB  - Previous studies demonstrated the involvement of astrocytes in the development of
      astrogliosis, a condition in which these cells undergo proliferation and
      hypertrophy. To examine whether astrocytes could migrate into lesions, we tested
      the influence of the murine chemokines MCP-1, KC, TCA3, and MIP-1 beta on
      migration of cultured neonatal mouse astrocytes. Subnanomolar concentrations of
      MCP-1 and KC were active chemoattractants indicating that these molecules were
      effective at physiologic concentrations. Specificity of MCP-1 was demonstrated by
      antibody inhibition and by the finding that the chemokine MIP-1 beta failed to
      induce astrocyte migration. The migratory responses were sensitive to pertussis
      toxin; this finding is consistent with involvement of G protein-coupled
      receptors. To examine the receptors for these chemokines further, we cloned the
      mouse homolog of the human MCP-1 receptor from a mouse peritoneal exudate cell
      cDNA library. The gene had 78% nucleotide sequence homology with the human MCP-1
      receptor (the nucleotide sequence of clone 1 encoding the mouse MCP-1 receptor
      can be obtained from the GenBank database, accession number U56819). However,
      reverse transcriptase-polymerase chain reaction (RT-PCR) failed to detect message
      for either the MCP-1 or KC receptors in astrocytes. The combined data suggest
      that mouse astrocytes use novel receptors to recognize these chemokines.

PMID- 8872900
TI  - Production of tumor necrosis factor-alpha as a result of glia-T-cell interaction
      correlates with the pathogenic activity of myelin basic protein-reactive T cells
      in experimental autoimmune encephalomyelitis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has attracted the greatest attention as a
      major factor in experimental autoimmune encephalomyelitis (EAE) pathogenesis. We
      compared rats undergoing EAE with manipulated but healthy animals by examining
      TNF-alpha gene expression in cells recovered from the brain. We used reverse
      transcriptase-polymerase chain reaction (RT-PCR) as a sensitive assay for
      detection and Northern blot hybridization as a reliable quantitative assay of TNF
      alpha mRNA. TNF-alpha gene expression was consistently detected in rats immunized
      with myelin basic protein (MBP) emulsified in complete Freund adjuvant (CFA), but
      not in rats immunized with MBP emulsified in incomplete Freund adjuvant (IFA),
      which does not induce EAE. Similarly, brain-derived cells from rats injected with
      cloned encephalitogenic T cells contained increased amounts of TNF-alpha mRNA
      compared with rats injected with nonencephalitogenic T cell clones similar in
      antigen specificity and in vitro lymphokine-producing capacity. Considering that
      the differing pathogenic capacity of MBP-reactive T cells might result from
      differing patterns of interaction with glia, we examined the impact of T-cell
      glia interaction in vitro on cytokine gene expression in both cell types. Glial
      components were efficient in inducing TNF-alpha expression in T cells; T cells
      and T-cell-derived cytokines could elicit expression of several lymphokine genes
      in glial cells. Comparison of RT-PCR and blot hybridization assays, however,
      suggested that cytokine expression was much more efficient, on a per cell basis,
      in T cells than in glia. TNF-alpha was shown to have direct cytotoxic effect on
      glial cells, which was greatly enhanced by small amounts of interferon-gamma (IFN
      gamma).

PMID- 8872899
TI  - Expression of the activation marker urokinase plasminogen-activator receptor in
      cultured human central nervous system microglia.
AB  - The ability of microglia to migrate through central nervous system (CNS) tissue
      requires proteolytic degradation of components of the extracellular matrix.
      Urokinase plasminogen activator (uPA), when bound to its cell surface receptor
      (uPAR), is an active cell surface protease. uPAR expression has been associated
      with cell activation. Cultured human microglia express surface uPAR. uPAR
      expression was found to be associated predominately with spindle- or
      bipolarshaped microglia. The addition of lipopolysaccharide (LPS) to microglial
      cultures enhanced the proportion of uPAR expression and shifted cell morphology
      to the elongated spindle or bipolar shape. When microglia were examined
      immediately ex vivo, uPAR surface expression could not be detected. Similarly,
      uPAR transcripts detected by reverse transcription-polymerase chain reaction
      techniques were found in cultured, but not ex vivo, microglia. Microglia isolated
      from a patient with multiple sclerosis (MS) displayed a large amount of uPAR+
      cells. These cells were predominantly spindle or bipolar in nature. These
      findings suggest that uPAR surface expression is associated with microglial
      activation. Surface expression of uPAR and associated cell surface protease
      activity may provide a mechanism for microglial migration and may be important in
      the pathophysiology of MS.

PMID- 8872902
TI  - Decreased CNS inflammation and absence of clinical exacerbation of disease after
      six months oral administration of bovine myelin in diseased SJL/J mice with
      chronic relapsing experimental autoimmune encephalomyelitis.
AB  - Murine chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) is a
      model of inflammatory demyelinating disease of the central nervous system (CNS)
      with similarity to multiple sclerosis (MS) in humans. Mice with confirmed
      neurologic deficits from CR-EAE were treated by oral administration of whole
      bovine myelin to investigate the effect of long-term oral delivery of myelin
      antigens on clinical disease and on the inflammatory response in the CNS. EAE
      positive mice were fed doses of 1 mg, 10 mg, or 20 mg of bovine myelin every
      other day for 6 months. We found that prolonged oral delivery of neuroantigen
      suppressed inflammatory and demyelination foci in the CNS of myelin-treated mice
      with no exacerbation of clinical disease status compared with the control group.
      Analysis of histologic sections of brain and spinal cords with hematoxylin-eosin
      (H&E) and Luxol fast blue (LFB) staining showed a decrease in the inflammatory
      cell infiltration and active centers of demyelination, respectively. Furthermore,
      after 6 months of treatment, there was no increased sensitization to myelin
      antigens seen, as measured by antimyelin basic protein (MBP) or anti-proteolipid
      apoprotein (PLP) antibodies. These results demonstrate that prolonged oral
      administration of myelin antigens in diseased animals has an ameliorating effect
      on the pathologic process and supports its potential long-term use in humans with
      MS.

PMID- 8872901
TI  - Inhibition of relapsing experimental autoimmune encephalomyelitis in SJL mice by
      feeding the immunodominant PLP139-151 peptide.
AB  - Peripheral antigen-specific tolerance can be induced by feeding protein antigens.
      The mechanism has been described as either clonal anergy/deletion or induction of
      antigen-specific regulatory cells that produce transforming growth factor-beta
      (TGF-beta). These two mechanisms have been linked to the magnitude and frequency
      of the dose of antigen fed; a single high dose induces anergy/deletion, whereas
      multiple low doses of antigen induce TGF-beta-secreting regulatory cells. In the
      present study, we investigated the mechanisms of feeding soluble peptides of
      proteolipid protein (PLP) for prevention of experimental autoimmune
      encephalomyelitis (EAE) induced by either intact PLP or the immunodominant PLP139
      151 peptide. Feeding PLP139-151 prevented acute and relapsing EAE induced by
      either PLP139-151 or intact PLP. PLP139-151 feeding induced anergy in the T
      helper 1 (Th1) population as measured by an inhibition of both proliferation and
      interferon-gamma (IFN-gamma) production. Interleukin-4 (IL-4) production was
      increased, but increased TGF-beta production was not observed. Importantly,
      PLP139-151 feeding induced anergy in peripheral and central nervous system (CNS)
      in-filtrating T cells. Feeding of the subdominant PLP epitope (PLP178-191) failed
      to inhibit EAE induced by PLP139-151; therefore, oral tolerance was not due to
      induction of bystander suppression. These results demonstrate that both acute and
      relapsing paralysis in EAE can be prevented by feeding the immunodominant peptide
      of PLP.

PMID- 8872903
TI  - Prevention and treatment of relapsing autoimmune encephalomyelitis with myelin
      peptide-coupled splenocytes.
AB  - Injection of antigen cross-linked accessory cells has proven to be an efficient
      and highly selective approach for inducing epitope-specific peripheral tolerance.
      This approach has been used successfully to inhibit induction of experimental
      autoimmune encephalomyelitis (EAE) and to dissect the relative dominance of
      component encephalitogenic determinants that contribute to both acute and
      relapsing EAE. In this study, we evaluated the tolerogenic effect of the dominant
      encephalitogenic epitope for SJL/J mice, residues 139-151 of myelin proteolipid
      protein (PLP), on the induction and relapses of EAE induced actively with PLP139
      151/CFA. Our results demonstrate the powerful protective effect of treating mice
      before induction of EASE with PLP139-151-conjugated splenocytes (SPL) on the
      incidence and severity of both the initial episode and the first relapse of EAE.
      Moreover, treatment of mice on the first day of onset of clinical signs of EAE
      reduced the severity of the first relapse, apparently by reducing T cell
      recognition of PLP139-151, although no significant therapeutic effect was
      observed during the initial treated clinical episode. These data demonstrate the
      utility of using neuroantigen-coupled accessory cells to prevent and treat
      relapsing EAE.

PMID- 8872904
TI  - Active immunization with complementary peptide PBM 9-1: preliminary evidence that
      it modulates experimental allergic encephalomyelitis in PL/J mice and Lewis rats.
AB  - The idiotype (Id) of T cells and possibly antibodies are involved in an Id
      network that may immunoregulate experimental allergic encephalomyelitis (EAE).
      Thus, the adoptive EAE in PL/J mice responding to myelin basic protein (MBP)
      peptide acetyl 1-9 can be modulated by monoclonal antibody (mAb) anti-Id
      generated by immunization with a peptide of inverted hydropathy to MBP peptide 1
      9, designated as PBM 9-1. A cross-reactive Id between species can be recognized
      on the T cell receptor (TCR) of Vb8.2 restricted T cells in either PL/J mice or
      Lewis rats. The present study was undertaken to examine the vaccine effect of PBM
      9-1 presented in the form of a multiple antigen peptide (MAP) to induce active
      immunity against active EAE in Lewis rats and active or adoptive EAE in PL/J
      mice. MAP-PBM 9-1 induced an antibody response in both Lewis rats and PL/J mice,
      but more in the former. A low level of anti-Id antibody, including a low level of
      reactivity with specific but not control T cells, was also detected in the sera
      collected before induction of or after recovery from EAE. Active immunization
      with MAP-PBM 9-1 had a protective effect on relapses of adoptive EAE in PL/J mice
      and could prevent active EAE in Lewis rats. A relationship was noted between the
      titer of serum anti-PBM 9-1 Ab and the protective effect of active immunization
      in Lewis rats. Although the mechanism of effect remains to be clarified, these
      results suggest that MAP-PBM 9-1 is a nonencephalitogenic candidate for
      protection against inflammatory demyelination.

PMID- 8872906
TI  - T-cell vaccination prevents EAE effector cell development but does not inhibit
      priming of MBP responsive cells.
AB  - Cell recipients which have recovered from adoptively transferred Experimental
      Allergic Encephalomyelitis (EAE) mediated by encephalitogenic T-cell lines do not
      develop clinical disease following subsequent challenge with myelin basic protein
      (MBP) emulsified in CFA (MBP-CFA), a recipient response termed vaccination. The
      immune mechanism(s), which accounts for the vaccination-induced resistance
      response, is not known. We have used an adoptive transfer system to investigate
      the point(s) of control within the pathway of EAE effector cell development from
      MBP-specific naive precursors that prevents clinical disease in T-cell line
      vaccinated, MBP-CFA challenged Lewis rats. Although EAE effector cells do not
      develop in T-cell line vaccinated recipients, our data shows that MBP precursor
      cells are primed in T-cell line vaccinated MBP-CFA challenged animals, and these
      MBP-specific precursor cells can be stimulated in culture to the EAE effector
      cell level. MBP-memory cells also arise in T-cell line vaccinated MBP-CFA
      challenged donors, as demonstrated by the early and rapid onset of EAE in MBP-CFA
      challenged recipients of lymphnode cells from T-cell line vaccinated MBP-CFA
      challenged donors. We also found that it was possible to adoptively transfer
      resistance to MBP-CFA challenge using spleen cells from donors previously
      vaccinated with encephalitogenic T-cells. These results show that although EAE
      effector cells do not develop in T-cell line vaccinated animals, T-cell
      vaccination does not inhibit the initial MBP precursor cell response and does not
      prevent the development of MBP memory cells.

PMID- 8872905
TI  - Encephalitogenic T cells are present in Lewis rats protected from autoimmune
      encephalomyelitis by coimmunization with MBP73-84 and its analog.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the
      central nervous system (CNS) that is mediated by T helper 1 (Th1) CD4+ T cells.
      Lewis rats can be protected from actively induced EAE by coimmunization with the
      encephalitogenic myelin basic protein (MBP) epitope 73-84 and its single alanine
      substituted analog 1028. Although analog 1028 cannot induce either active or
      passive EAE, it does elicit a Th1-like response that is cross-reactive with MBP73
      84. Analog 1028 can effectively inhibit clinical EAE in a dose-dependent manner
      when rats are coimmunized with the encephalitogenic peptide MBP73-84 and 1028 in
      complete Freund adjuvant (CFA). Stimulation of cells from MBP73-84:1028
      coimmunized protected rats proliferate and secrete interferon-gamma (IFN-gamma)
      and tumor necrosis factor-alpha (TNF-alpha) in vitro in response to MBP73-84.
      Furthermore, coimmunized protected rats harbor a population of MBP73-84-reactive
      potentially encephalitogenic T cells, because splenocytes from these rats can be
      stimulated to transfer passive EAE to naive recipients. Thus, the protection of
      coimmunized rats by analog 1028 is not due to the inhibition of priming of MBP73
      84-reactive T cells or alteration of the cytokine secretion profile of the MBP73
      84-reactive cell population. Rather, MBP73-84-reactive potentially
      encephalitogenic T cells are primed in these protected animals.

PMID- 8872907
TI  - Generation of autonomously pathogenic neo-autoreactive Th1 cells during the
      development of the determinant spreading cascade in murine autoimmune
      encephalomyelitis.
AB  - Chronic progression of autoimmune disease is accompanied by the acquisition of
      autoreactivity to new self-determinants. Recent evidence indicates that this
      process, commonly referred to as determinant spreading, may be pathogenic for
      chronicity. Our studies on experimental autoimmune encephalomyelitis (EAE), a
      murine model widely used in multiple sclerosis (MS) studies, have shown that
      determinant spreading develops as a predictable sequential cascade of neo
      autoimmunity during progression to chronic disease. By 7-8 weeks after
      immunization of (SWR x SJL)F1 mice with the immunodominant myelin proteolipid
      protein determinant (PLP 139-151), splenocytes consistently respond to the
      immunodominant myelin basic protein determinant (MBP 87-99). In the present
      study, we directly address the pathogenicity of neo-autoimmunity resulting from
      endogenous self-priming during the course of disease. Our results indicate that T
      cells responding to the spreading MBP 87-99 determinant produce a proinflammatory
      cytokine profile consistent with type 1 helper T cells (Th1) cells. In addition,
      splenocytes activated to the spreading MBP 87-99 determinant consistently
      transfer acute EAE in naive recipients even when T cells reactive to the priming
      PLP 139-151 immunogen are eliminated by bromodeoxyuridine (BUdR)-mediated
      photolysis. Our data indicate that endogenous neo-autoantigen priming during
      chronic autoimmune disease generates type 1 helper T cells (Th1) cells that are
      autonomously pathogenic. These results provide further evidence supporting the
      view that determinant spreading is a pathogenic process that leads to chronic
      progression of autoimmune disease.

PMID- 8872908
TI  - Active and passive experimental autoimmune encephalomyelitis in strain 129/J (H
      2b) mice.
AB  - Failure of C57BL/6J and C57BL/10Sn (H-2b) mice to exhibit clinical signs of
      experimental autoimmune encephalomyelitis following immunization with myelin
      basic protein (MBP) has been interpreted to indicate that mice of this haplotype
      are resistant to EAE. Recently, we immunized strain 129/J (H-2b) mice with rat
      MBP and found that clinical signs of EAE were expressed in the majority of
      animals within 2 to 3 weeks. Passive EAE was readily induced by adoptive transfer
      of MBP-specific T cell lines to syngeneic recipients. MBP peptide 89-101 and PLP
      peptide 178-191 induced EAE upon active immunization although proteolipid protein
      peptide 139-151 was ineffective in this regard. Strain 129/J mice never recovered
      fully from acute EAE, and signs of relapsing disease were not observed.

PMID- 8872909
TI  - Neonatal injection of Lewis rats with recombinant V beta 8.2 induces T cell but
      not B cell tolerance and increased severity of experimental autoimmune
      encephalomyelitis.
AB  - In Lewis rats with experimental autoimmune encephalomyelitis (EAE) mediated by V
      beta 8.2 effector cells, anti-idiotypic T cells and antibodies could be boosted
      by injection of V beta 8.2 peptides, inducing both T cells and antibodies that
      reduced the severity and shortened the course of disease. However, EAE in Lewis
      rats is self-limiting, and we sought to determine if the anti-idiotypic response
      contributed to the natural recovery process. In a previous study, we found that
      adult tolerance induced to one of the regulatory idiotopes, V beta 8.2-44-54,
      caused worsening of EAE, implicating response to this epitope in recovery from
      EAE. However, neonatally-induced tolerance to V beta 8.2-44-54 did not alter the
      course of EAE, suggesting either compensation by additional V beta 8.2
      determinants, or mechanistic differences in tolerization protocols. In this
      report, we reevaluate the role of V beta 8.2 determinants in recovery from EAE,
      using two recombinant V beta 8.2 constructs to induce neonatal tolerance to the
      comprehensive set of V beta 8.2 epitopes prior to adult induction of EAE. We
      found that neonatal exposure to either of the recombinant V beta 8.2 molecules
      induced "split" tolerance-specific T cell tolerance but enhanced antibody
      responses- and a more severe course of EAE. In contrast, neonatal exposure to a V
      beta 8.2 + T cell hybridoma or a control protein did not induce T cell tolerance
      to V beta 8.2 determinants and did not alter the EAE disease course. These
      results are consistent with those obtained by inducing adult tolerance, and
      suggest that our previous result (normal recovery from EAE in rats neonatally
      tolerized to V beta 8.2-44-54) was probably due to a compensatory response to
      other V beta 8.2 determinants. In both studies, the data clearly implicate T cell
      recognition of V beta 8.2 determinants in the natural EAE recovery process.

PMID- 8872910
TI  - Adaptation of TCR expression vectors for the construction of mouse-human chimeric
      MBP-specific TCR transgenes.
AB  - T cell receptor (TCR) transgenic mice have been used extensively to study T cell
      development in vivo. Such studies have demonstrated high levels of expression of
      the TCR transgenes. Although a number of human T cell receptors appear to play a
      role in the development of autoimmune diseases, in vitro studies have proven
      inadequate for investigation of their putative pathogenicity. Several groups have
      reported the isolation of myelin basic protein (MBP)-reactive T cell clones from
      patients with multiple sclerosis and many of the T cell receptors from such
      clones have been well characterized. Since a number of inbred mouse strains have
      demonstrated susceptibility to a similar T cell-mediated inflammatory
      demyelinating disease known as EAE, a useful animal model is likely to be
      generated by expressing human MBP-specific TCR in susceptible mice. As a first
      step toward this goal we have cloned a number of TCR genes into an expression
      vector previously used for murine TCR genes. Here we report the development of a
      rapid cloning system for the generation of mouse-human chimeric TCR transgene
      constructs and the use of this system for the production of MBP-specific TCR
      transgenes. Human MBP-specific TCR transgenic mice will provide a unique system
      for the investigation of T cell-mediated demyelinating disease in the central
      nervous system (CNS).

PMID- 8872911
TI  - Evidence against chronic antigen-specific T lymphocyte activation in myasthenia
      gravis.
AB  - Myasthenia gravis (MG) is an antigen-specific autoimmune disease caused by
      antibodies against acetylcholine receptors (AChR) at the post-synaptic membrane
      of the neuromuscular junction. Clinical and immunological data imply the
      involvement of AChR-specific T lymphocytes as helper cells for autoantibody
      production. Direct data to support this hypothesis, however, remain sparse. In
      the present study, a large population of MG patients was studied for evidence of
      peripheral blood T cell activation by several assays. Assays based on non
      specific measurements of T cell activation as well as assays of antigen-specific
      clonal expansion were utilized. Levels of soluble IL-2 receptor in serum were
      modestly elevated in some patients, suggesting T cell activation. However,
      peripheral blood cells did not show evidence of IL-2 receptor expression or
      enhanced reactivity to IL-2 in culture. Clonable T cells selected for
      hypoxanthine phosphoribosyl transferase (hprt) mutation, another non-antigen
      specific marker for T cell activation, were not seen with increased frequency
      except in patients treated with purine analogs. Antigen-specific T cell
      activation was measured by proliferation assays using heterologous and autologous
      sources of AChR. Antigen-restimulated peripheral blood cell cultures were cloned
      by limiting dilution. The vast majority of patients failed to show convincing
      evidence of AChR specific T cell activation or clonal expansion; only 2 of 44
      patients demonstrated clonable autologous AChR-specific T cells. An alternative
      hypothesis of T cell involvement in MG is proposed in which T cell activation is
      discontinuous and predominantly directed at antigens other than AChR.

PMID- 8872912
TI  - Vaccination with autoreactive T cell clones in multiple sclerosis: overview of
      immunological and clinical data.
AB  - Although the etiology and pathogenesis of Multiple Sclerosis (MS) remain elusive,
      accumulating evidence indicates that MS is a chronic inflammatory disease with an
      autoimmune component, mediated by autoreactive T lymphocytes specific for myelin
      antigens. The triggering T cell autoantigen has not been identified yet, but
      recent immunological studies in MS and parallel experiments in experimental
      allergic encephalomyelitis (EAE), the animal model of MS, have indicated that
      myelin basic protein (MBP) can be considered as one of the major candidate
      autoantigens in the pathogenesis of the disease. Based on these observations,
      several therapeutic strategies have been developed aimed at the specific
      elimination or inactivation of MBP reactive T cells in MS. One of these
      approaches involves the immunization of MS patients with autologous attenuated
      autoreactive T cells to induce an immune response specifically targeted at these
      autoreactive T cells. This method, termed T cell vaccination, has been shown to
      prevent and treat EAE. We have recently conducted a pilot trial of T cell
      vaccination in a limited group of MS patients to evaluate the immunological
      responses to the injected cells. The data obtained indicate that this type of
      vaccination induces an effective anti-clonotypic T cell response leading to a
      specific depletion of circulating MBP reactive T cells. Preliminary data on the
      clinical effects are promising, encouraging further clinical trials.

PMID- 8872913
TI  - Modifications in plasma lipoprotein concentration and lipid composition regulate
      the biological activity of hydrophobic drugs.
AB  - The maximum tolerated dose and pharmacokinetics of a drug is usually determined
      in healthy human volunteers and animals. This data is then used to define the
      dosing recommendation for the diseased patient population. However, in the case
      of some hydrophobic drugs, the dose which is deemed nontoxic becomes ineffective
      and/or toxic when administered to the diseased patient. This observation might be
      explained by several lines of evidence which indicate that binding of drugs such
      as amphotericin B (AmpB) and cyclosporine (CSA) to plasma low-density lipoprotein
      (LDL) cholesterol is involved in the development of kidney toxicity. Our
      preliminary studies have suggested that this phenomena might be due to increase
      lipid transfer protein (LTP 1) activity which promotes the transfer of AmpB from
      high-density lipoproteins to LDL. In addition, since LTP 1 function is regulated
      by the lipid content of plasma lipoproteins, we suggest that changes in
      lipoprotein composition that occur in dyslipidemia regulate the distribution of
      these and other hydrophobic drugs (i.e., annamycin and nystatin). The impact of
      these studies on hydrophobic drug therapy could have broad implications on how we
      evaluate and determine dosing of hydrophobic drugs in dyslipidemic patients. By
      understanding the mechanism(s) responsible for the distribution of hydrophobic
      compounds in the bloodstream, we are trying to define the effect of dyslipidemias
      on the plasma clearance and therapeutic index of hydrophobic compounds.

PMID- 8872914
TI  - Porcine coronary artery pharmacodynamics in vitro evaluated by a new
      intravascular technique: relation to axial stretch.
AB  - A new intravascular balloon catheter-based technique, impedance planimetry and
      the wire-mounted isometric tension technique commonly employed to study vessel
      pharmacodynamics in vitro, were compared. Porcine left anterior descendent
      coronary artery reactivity to nifedipine was assessed and the influence of 20%
      axial stretch was investigated. There were no histological differences between
      segments where the impedance planimetry balloon had been inflated and untouched
      segments. EC50 values differed significantly between the three procedures
      applied: The isometric method (n = 7): 2.54 +/- 0.44.10(-9) M; nonstretched
      arteries by the impedance planimetric method (n = 7): 1.99 +/- 0.40.10(-8) M;
      arteries 20% axially stretched (n = 7): 2.00 +/- 1.36.10(-7)M (isometric and
      nonstretched: p < 0.05; isometric and stretched: p < 0.001; nonstretched and
      stretched: p < 0.05). Maximal relaxant responses to nifedipine were 91.8 +/- 2.1%
      (isometric method), 105.1 +/- 2.3% (nonstretched), and 104.9 +/- 7.7% (stretched)
      (ANOVA, p = 0.11). In stretched arteries, the initial 12-min response to an
      increased dose of nifedipine was more rapid than the response of nonstretched
      arteries at a concentration of 1.10(-7) M (p = 0.038) and had a nonsignificant
      tendency toward a more rapid response at other concentrations. Resting tone could
      not be demonstrated and time control experiments showed no change in the maximal
      vessel response to potassium with any of the three methods. A new method in the
      evaluation of artery pharmacodynamics in vitro was presented. The study
      demonstrated that axial stretching of an artery has impact on the pharmacodynamic
      reactivity to nifedipine in porcine coronary arteries. Further studies are needed
      to evaluate the impact of the method on endothelial function.

PMID- 8872915
TI  - A flow-cytometric method to evaluate drug antiaggregating effect on rat
      neutrophils.
AB  - Neutrophils are one of the first cellular populations to become involved in
      inflammatory processes and some features of the response to inflammatory stimuli
      can be partially reproduced in vitro by treatment with chemotactic peptides such
      as N-formyl-methionyl-leucyl-phenylalanine (FMLP). Nonsteroidal antiinflammatory
      drugs (NSAIDs), such as indomethacin, are known to interfere in vitro with human
      and rat neutrophil functions and to inhibit FMLP-induced aggregation. In this
      article we define the scatter parameters of rat neutrophils and demonstrate that
      flow-cytometric analysis of these cells can be used to analyze the inhibiting
      action of drugs in an in vitro model of aggregation. We show, in fact, that
      indomethacin at 100 microM (p < 0.05) and 200 microM (p < 0.01) is able to
      significantly reduce rat neutrophil aggregation. These results confirm the data
      obtained by light transmittance aggregometry and indicate that cytometric
      analysis of aggregation phenomena is a technique suitable for the screening of
      antiaggregating drugs.

PMID- 8872916
TI  - Dimethyl sulfoxide/propylene glycol is a suitable solvent for the delivery of
      diazepam from osmotic minipumps.
AB  - The functional integrity of Alzet osmotic minipumps was assessed using two
      organic solvents (50% (v/v) dimethyl sulfoxide (DMSO)/50% (v/v) propylene glycol
      (PG) and 100% tetraglycol) which dissolve diazepam, an aqueous insoluble
      benzodiazepine. Both solvents showed a significant decrease in output rate over
      time: the decline with tetraglycol was, however, more marked and variable.
      Further, the DMSO/PG vehicle demonstrated a comparable decline in rate (1.45%) to
      that of the control vehicles saline and water (1.12%). DMSO/PG is therefore a
      suitable solvent for the chronic delivery of diazepam from osmotic minipumps.

PMID- 8872917
TI  - Rapid determination of in vivo and in vitro antibody responses by suspension
      hemolytic assay.
AB  - A suspension hemolytic (SH) assay newly modified in this laboratory was applied
      to the measurement of primary IgM antibody responses, such as T-dependent, T
      independent, and polyclonal B cell responses in in vivo and in vitro assays. All
      results of the SH assay were equal to those of the conventional plaque-forming
      cell (PFC) assay. With the SH assay in in vitro assays, we could separately
      measure the amount of the IgM that had been produced during the whole
      immunization period and measure the IgM newly produced during the shorter time of
      the assay. The immunomodulations by dioxin and glycopeptide were accurately
      evaluated by the SH and the PFC assay. Our study suggested that the SH assay
      modified in this laboratory was more advantageous because of the simplicity of
      the assay and better analysis of data than the PFC assay, and could be used as
      the primary method in studying the effects of pharmaceutical and toxic agents on
      humoral immune functions.

PMID- 8872918
TI  - A rapid beta-NADH-linked fluorescence assay for lactate dehydrogenase in cellular
      death.
AB  - Lactate dehydrogenase (LDH) release in a common marker of cellular death.
      Traditionally, the fraction of LDH released has been measured using a NADH-linked
      UV-Vis spectrophotometric method. The limitation of this method is that samples
      are usually run serially and thus is time intensive. Therefore, we developed a
      NADH-linked LDH assay using a fluorescence plate reader that had a correlation of
      0.95 with the traditional UV-Vis spectrophotometric method. Using rabbit renal
      proximal tubule suspensions at a concentration of 1 mg cellular protein/ml of
      media, the fluorescence assay can determine LDH release in 22 samples in 2 min
      using 12 microL of cellular homogenates and 150 microL of media. The parallel
      processing of samples and smaller volumes used in the fluorescence assay results
      in decreased analysis time and costs.

PMID- 8872919
TI  - Isolation and primary culture of rat cerebral microvascular endothelial cells for
      studying drug transport in vitro.
AB  - To establish the cerebral microvascular endothelial cell (CMEC) culture system
      for animals commonly utilized in in vivo studies, we developed a method for
      isolation and culture of rat CMECs, and the model system was used in preliminary
      in vitro transport experiments. The isolated rat brains were minced. After an
      incubation with dispase, a fraction of microvessels was obtained by the dextran
      gradient. The tissue was filtered and dissociated using collagenase/dispase.
      After the enzyme treatment, the microvessels were layered onto the top of Percoll
      gradient and centrifuged for purification. Specific enzyme activities of alkaline
      phosphatase and gamma-glutamyltransferase in the preparations gradually increased
      as the isolation process progressed. The isolated cells reached confluence after
      5-7 days in culture. The cultured cells had Factor VIII-related antigen and an
      uptake of acetylated-low density lipoprotein labeled with 1,1'-dioctadecyl-3,3,
      3',3'-tetramethyl-indocarbocyamine perchlorate (Dil-Ac-LDL). In the transport
      studies, thawed cells after several months under -80 degrees C were used. The
      cultured cells after the freezing preservation also had CMEC characteristics, the
      same as the cells seeded immediately after isolation. The permeability of [14C]
      mannitol, an impermeable marker for blood-brain barrier, was considerably reduced
      when the cell monolayer was present. The transport of [3H]3-O-methyl-D-glucose
      was significantly inhibited by the unlabeled compound. Furthermore, 2,4
      dinitrophenol, an uncoupler of oxidative phosphorylation, significantly
      diminished the transport of [3H]L-proline. These results indicated that the cell
      monolayer obtained in the present study could be applicable to drug transport
      studies through the blood-brain barrier in vitro.

PMID- 8872920
TI  - Characterization of [3H]apafant binding to PAF receptor on rabbit platelet
      membranes: a comparison of a microplate filtration system and a standard method.
AB  - This article describes the application of a Microplate Filtration System (MFS) to
      a binding assay, with the results being compared to those obtained with a
      conventional 24-Well Filtration Manifold (24WFM). The data reported here
      characterize the PAF receptor on rabbit platelet membranes using [3H]apafant. The
      results showed that [3H]apafant labelled a homogenous population of high-affinity
      binding sites in a concentration-dependent manner. Binding was very specific,
      saturable, reversible, and proportional to receptor concentration. [3H]Apafant
      interacted with membranes in an apparently competitive manner, with pseudo-Hill
      coefficients not significantly different from unity, thus indicating that apafant
      did not interact cooperatively at these binding sites. A number of PAF
      antagonists (apafant, lexipafant, BN-52021, SCH-37370, SR-27417, UR-12670)
      inhibited [3H]apafant binding with slopes near unity and with a rank order of
      potency in good agreement with their ability to inhibit PAF-induced rabbit
      platelet aggregation, suggesting that the sites labelled are functional PAF
      receptors. C18-PAF also competed with [3H]apafant for the receptor, but yielded
      biphasic inhibition curves which could be resolved into high- and low-affinity
      components. No significant differences were found either in the equilibrium
      binding parameters or in the PAF antagonists affinities obtained with the 24WFM
      and the MFS. The use of the latter system improved sample handling efficiency and
      shortened overall labor time, thus representing a more suitable way to perform
      receptor binding assays.

PMID- 8872921
TI  - Tensile properties of the superior glenohumeral and coracohumeral ligaments.
AB  - Recent evidence has shown that the superior glenohumeral ligament (SGHL) and
      coracohumeral ligament (CHL) are important static stabilizers. To clarify the
      function of these two ligaments, we studied their tensile properties with bone
      ligament-bone complexes from fresh-frozen shoulders, 10 SGHLs and 10 CHLs. Each
      ligament's cross-sectional area was measured, and uniaxial tensile testing of
      each complex was performed. The stiffness, ultimate load, percent elongation, and
      energy absorbed to failure of each bone-ligament-bone complex were derived from
      its load-elongation curve. The cross-sectional area of the coracohumeral ligament
      was significantly greater than that of the superior glenohumeral ligament of
      their midportions (CHL, 53.7 +/- 3.2 mm2 vs. SGHL, 11.3 +/- 1.6 mm2, p < 0.05).
      Results also reveal significant differences between the tensile properties for
      the two ligaments, with the coracohumeral ligament possessing greater stiffness
      (CHL, 36.7 +/- 5.9 N/mm vs. SGHL, 17.4 +/- 1.5 N/mm, p < 0.05) and ultimate load
      (CHL, 359.8 +/- 40.3 N vs. SGHL, 101.9 +/- 11.5 N, p < 0.05) than the superior
      glenohumeral ligament. Our findings confirm that the coracohumeral ligament is an
      important capsuloligamentous structure of the glenohumeral joint.

PMID- 8872922
TI  - Role of the long head of the biceps brachii in glenohumeral stability: a
      biomechanical study in cadavera.
AB  - Ten cadaveric shoulders were tested to evaluate the effect of simulated
      contraction of the long head of the biceps brachii on glenohumeral translation.
      The shoulders were mounted on a special apparatus attached to a servo-controlled
      hydraulic testing device. Sequential 50 N anterior, posterior, superior, and
      inferior forces and a 22 N joint compressive load were applied to the shoulders.
      An air cylinder applied a constant force to the tendon of the long head of the
      biceps brachii. The shoulders were tested in seven positions of glenohumeral
      elevation and rotation. Application of a force to the long head of the biceps
      brachii resulted in statistically significant decreases in humeral head
      translation. The influence of the long head of the biceps was more pronounced at
      middle and lower elevation angles. When the shoulder was placed in 45 degrees of
      elevation and neutral rotation, application of a 55 N force to the biceps tendon
      reduced anterior translation by 10.4 mm (p = 0.001), inferior translation by 5.3
      mm (p = 0.01), and superior translation by 1.2 mm (p = 0.004).

PMID- 8872923
TI  - Strength of the glenoid labrum and adjacent shoulder capsule.
AB  - This study evaluates the role of the glenoid labrum and capsule in the prevention
      of shoulder dislocation. Fifteen shoulder joints from nine fresh cadavers were
      used. The labrum and capsule were cut into sections 5 mm wide, and the strength
      of each slice to rupture was measured. The rupture site was observed
      microscopically. The anterior-inferior portion was the weakest, with a mean force
      necessary to cause rupture of 3.84 +/- 1.00 kg/5 mm. The rupture site was the
      portion of the labrum close to the cartilage of the glenoid. Histologic structure
      and degenerative changes of the labrum did not differ in the anterior to
      posterior portions. These results show that the anterior-inferior portion of the
      labrum is relatively weak. This finding may explain the lesion commonly
      identified in anterior shoulder dislocation.

PMID- 8872924
TI  - Inferior glenohumeral ligament: geometric and strain-rate dependent properties.
AB  - The inferior glenohumeral ligament (IGHL) is an important structure for
      maintaining shoulder stability. This study was aimed at determining the geometric
      and anatomic characteristics of the IGHL and its tensile properties at a higher
      strain rate than previously tested. Eight fresh-frozen human cadaver shoulders
      (average age 69 years, age range 62 to 73 years) from four female and four male
      cadavers were used to harvest bone-ligament-bone specimens from the three regions
      of the IGHL (superior band, anterior axillary pouch, and posterior axillary
      pouch). Uniaxial tensile tests were performed at the moderately high strain rate
      of approximately 10% per second with a servo-hydraulic testing machine. This
      represented a strain rate that was approximately 100 to 1000 times faster than
      that previously reported. During tensile testing, bone-ligament-bone strains were
      calculated from grip-to-grip motion on the testing machine, and mid-substance
      strains were determined by a video dimensional analyzer. Although all regions of
      the IGHL had similar lengths (averaging 43.4 mm), their thickness varied by
      region and by proximal-to-distal location. The superior band was the thickest
      (2.23 +/- 0.38 mm) of the three regions. Of the remaining two regions the
      anterior axillary pouch (1.94 +/- 0.38 mm) was thicker than the posterior
      axillary pouch (1.59 +/- 0.64 mm). By proximal-to-distal location the IGHL was
      thicker for all three regions near the glenoid (2.30 +/- 0.57 mm) than near the
      humerus (1.61 +/- 0.52 mm). The superior band had a greater stiffness (62.63 +/-
      9.78 MPa) than either the anterior axillary pouch (47.75 +/- 17.89 MPa) or the
      posterior axillary pouch (39.97 +/- 13.29 MPa). Tensile stress at failure was
      greater in the superior band (8.4 +/- 2.2 MPa) and the anterior axillary pouch
      (7.8 +/- 3.1 MPa) than the posterior axillary pouch (5.9 +/- 1.7 MPa). The
      anterior axillary pouch demonstrated greater bone-to-bone and mid-substance
      strains (30.4% +/- 4.3% and 10.8% +/- 2.4%, respectively) before failure than the
      other two regions (superior band: 20.8% +/- 3.8% and 9.1% +/- 2.8%, respectively;
      posterior axillary pouch: 25.2% +/- 5.8% and 7.8% +/- 2.6%, respectively). Bone
      to-bone strain was always greater than mid-substance strain, indicating that when
      the IGHL is stretched, the tissue near the insertion sites will experience much
      greater strain than the tissue in the mid-substance. insertion failures were more
      likely at slower strain rates, and ligamentous failures were predominant at the
      fast strain rate. When compared with other tensile studies of the IGHL at slower
      strain rates (0.01% per second and 0.1% per second), the superior band and the
      anterior axillary pouch demonstrated the viscoelastic effects of increased
      stiffness and failure stress. This superior band and anterior axillary pouch
      pouch viscoelastic stiffening effect suggests that these two regions may function
      to restrain the humeral head from rapid abnormal anterior displacement in the
      clinically vulnerable position of abduction and external rotation.

PMID- 8872925
TI  - Magnetic resonance arthrography in the assessment of anterior instability of the
      shoulder: comparison with double-contrast computed tomography arthrography.
AB  - Forty-seven shoulders with traumatic anterior instability were studied by
      magnetic resonance arthrography (MRA) and computed tomography arthrography (CTA)
      to compare the diagnostic performance of these examinations in the evaluation of
      Bankart lesions. All shoulders were examined by arthroscopy to verify the
      lesions. Labral damage evaluated by MRA and by CTA correlated significantly with
      arthroscopic findings (MRA, r = 0.55, p < 0.0001; CTA, r = 0.45, p = 0.0050). MRA
      possessed higher sensitivity in detecting torn labra (MRA, sensitivity = 87%,
      specificity = 75%; CTA, sensitivity = 33%, specificity = 88%). In detecting
      displaced labra, sensitivity and specificity were 65% and 94% for MRA and 75% and
      69% for CTA. The inferior glenohumeral ligament was depicted as a lax structure
      in 74% by MRA but in only 21% by CTA. We conclude that MRA is superior to CTA in
      detecting lesions associated with shoulder instability.

PMID- 8872926
TI  - Translation of the glenohumeral joint with the patient under anesthesia.
AB  - This study was undertaken to determine glenohumeral translation in the
      anesthetized patient. Radiographically assessed humeral translation was measured
      in 18 members of a control group, 10 patients with anterior instability, and 10
      patients with multidirectional instability. In the control group stress
      radiographs revealed anterior translation of 17% (percentage of the diameter of
      the glenoid from anterior to posterior), posterior of 26%, and inferior to 29%
      (percentage of diameter of glenoid from superior to inferior). In patients with
      anterior instability anterior translation was 29%, posterior translation was 21%,
      and inferior translation was 49%. In patients with multidirectional instability
      anterior translation was 28%, posterior translation was 52%, and inferior
      translation was 46%. Overlap in translation was seen between normal members and
      those with instability. The most practical method to grade anterior and posterior
      translation of the humeral head within the glenoid fossa involves a clinical
      assessment of where the center of the humeral head rests in reference to the
      glenoid rim.

PMID- 8872927
TI  - Bony changes of the glenoid as a consequence of shoulder instability.
AB  - Among 500 skeletons of mature individuals, 27 showed signs of shoulder
      instability as indicated by the presence of a glenoid rim avulsion fracture, a
      bony Bankart lesion, with an anterior or posterior Hill-Sachs defect. Twenty-two
      of these glenoid lesions were anterior, and five were posterior. This is a higher
      prevalence than reported in clinical studies. With few exceptions the pathologic
      changes in the bony glenoid were well circumscribed and not found in conjunction
      with diffuse arthritic changes. These findings do not support prophylactic
      shoulder stabilization to avoid the development of arthritic changes of a
      generalized and major degree.

PMID- 8872928
TI  - Use of vertebral levels to measure presumed internal rotation at the shoulder: a
      radiographic analysis.
AB  - Internal rotation of the shoulder is frequently measured by noting the maximal
      vertebral level reached by the patient's thumb, but it is not at all certain that
      this maneuver is strictly measuring internal rotation. We analyzed this maneuver
      with computed tomographic scans of the shoulder in differing positions. We also
      analyzed extension of the glenohumeral joint and scapulothoracic articulation
      with scapular lateral radiographs. Finally, we used posteroanterior radiographs
      to analyze elbow flexion at the limits of internal rotation behind the back. We
      found that maximal internal rotation behind the back occurs in approximately a 2
      : 1 ratio between the glenohumeral joint and the scapulothoracic articulation.
      However, the scapulothoracic articulation was more significant in placing the arm
      behind the back, whereas the glenohumeral joint performed most of the internal
      rotation in front of the body. The scapulothoracic articulation assists in this
      motion by both extension and internal rotation of the scapula on the thorax. The
      limits of internal rotation behind the back are reached with a significant
      contribution from elbow flexion. We conclude that measuring shoulder internal
      rotation by the maximal vertebral level reached by the patient's thumb greatly
      oversimplifies the concept of internal rotation and that limitations in this
      motion may not be strictly due to a loss of internal rotation at the glenohumeral
      joint.

PMID- 8872929
TI  - Lag signs in the diagnosis of rotator cuff rupture.
AB  - We assessed the relative value of lag signs for the evaluation of rotator cuff
      rupture in a prospective study of 100 consecutive painful shoulders with
      impingement syndrome, stages 1 to 3. Lag signs were compared with the Jobe and
      lift-off signs. Three tests were designed to assess the main components of the
      rotator cuff: the external rotation lag sign (ERLS) for the supraspinatus and the
      infraspinatus tendons, the drop sign for the infraspinatus, and the internal
      rotation lag sign (IRLS) for the subscapularis tendon. For assessment of the
      supraspinatus and infraspinatus the ERLS was less sensitive but more specific
      than the jobe sign. The drop sign was the least sensitive but was as specific as
      the ERLS. Partial ruptures of the supraspinatus remained concealed to the ERLS.
      For assessment of the subscapularis the IRLS was as specific but more sensitive
      than the lift-off sign. Partial ruptures of the subscapularis tendon could be
      missed by the lift-off sign but were detected by the IRLS. The magnitude of the
      lag correlated with the size of the rupture for both the ERLS and the IRLS.
      Clinical testing for lag signs was efficient, reproducible, and reliable. In
      patients with little or no restriction of motion it enhanced the accuracy of
      clinical diagnosis in rotator cuff lesions.

PMID- 8872930
TI  - Relationship between calcifying tendinitis and subacromial impingement: a
      prospective radiography and magnetic resonance imaging study.
AB  - In a prospective study radiographs and magnetic resonance images of 75 patients
      with calcifying tendinitis of the rotator cuff were analyzed. The aim was to
      evaluate any relation between calcifying tendinitis and subacromial impingement.
      A total of 83% of the calcifications were located in the supraspinatus or the
      adjoining part of the subscapularis tendon. On T1-weighted images they could be
      demonstrated with high accuracy as areas of decreased signal intensity. A
      magnetic resonance imaging categorization of the calcium deposits was carried out
      by means of a differentiation of form, outline, and density. A partial rotator
      cuff tear was found in one shoulder; in 11% variable aspects of degenerative
      alteration of the affected tendon were seen. By analysis of the radiographic
      outlet view 16% of the cases had a type III acromion. In conclusion, little
      correlation exists between calcifying tendinitis and additional findings
      associated with subacromial impingement.

PMID- 8872931
TI  - Coronal plane geometry of the proximal humerus relevant to prosthetic
      arthroplasty.
AB  - Most prosthetic designs for the replacement of the proximal humerus have one head
      shaft angle and several head sizes allowing limited replication of the anatomy.
      The necessity for press fit designs to follow the reamed canal adds an additional
      constraint. To better understand these limitations, this study measures proximal
      humeral anatomy in relationship to the surgically reamed canal. Measurements were
      made from radiographs of 21 humeri. Radius of curvature averaged 25.3 mm, head
      height 18.5 mm, head-shaft angle 40.7 degrees, and offset 9.7 mm. Longer humeri
      had proportionally larger shafts and larger heads (r = 0.7, p < 0.0005). Proximal
      humeral anatomy is extremely variable. The relatively fixed geometry of most
      prosthetic systems limits the surgeon's ability to replicate the original
      anatomy. As a generalization for existing press fit, modular systems, the surgeon
      must either position a similarly sized prosthetic articular surface superomedial
      to that of the original anatomy or use one with less articular surface area.

PMID- 8872932
TI  - Bony avulsion of the pectoralis major muscle.

PMID- 8872933
TI  - Compression of the lateral antebrachial cutaneous nerve by the biceps tendon.

PMID- 8872934
TI  - Management of antebrachial deformity and shortening secondary to a synostosis in
      a dog.
AB  - A nine-week-old labrador was presented with a deformed left forelimb causing
      obvious lameness. Radiographs suggested that the dog had suffered a fracture
      involving the radius and ulna which had healed resulting in a synostosis. There
      was a concurrent radial physeal injury. The dog was treated initially by
      osteotomy of the radius and ulna stabilised using a static external skeletal
      fixator. At a subsequent surgery lengthening of the limb was achieved by using an
      Ilizarov apparatus. Worsening carpal hyperflexion was managed by bandaging in
      forced extension. A successful outcome was achieved with a final result of a 24
      per cent discrepancy in length between the two radii at 17 months of age. An
      increase in length of the ipsilateral humerus was seen in association with the
      shortened forelimb.

PMID- 8872935
TI  - Prevalence of bacteria in the conjunctival sac and on the eyelid margin of
      clinically normal cats.
AB  - Samples from the palpebral conjunctive, third eyelid and eyelid margin from 50
      asymptomatic cats were analysed. Sixty-seven per cent of the samples showed
      bacterial growth with a high predominance of the genus Staphylococcus (97.8 per
      cent). The most frequent species was S epidermidis (45.7 per cent), followed by S
      simulans (23.9 per cent), S auricularis (17.4 per cent) and S saprophyticus (6.5
      per cent). Three samples of S aureus (6.5 per cent) and one of Pseudomonas
      aeruginosa (2.1 per cent) were also identified. The role of these microorganisms
      in the eyes of cats is discussed and the importance of the new species
      Staphylococcus felis is stressed.

PMID- 8872936
TI  - Laboratory diagnosis of insulinoma in the dog: a retrospective study and a new
      diagnostic procedure.
AB  - Simultaneous insulin and glucose measurements from a single sample are often
      insufficient for the laboratory diagnosis of insulinoma in the hypoglycaemic dog.
      Although the simple insulin (microU/litre): glucose (mmol/litre) ratio is best,
      when the selected threshold is set at 13.5, it is not always efficient to confirm
      or refute insulinoma. The fasting test consists of collecting four samples on a
      given day (no accurate time period is set between any two samples) from a fasting
      dog for simultaneous insulin and glucose measurements to detect at least one
      abnormal insulinaemia peak.

PMID- 8872937
TI  - Tolfenamic acid in the control of ocular inflammation in the dog:
      pharmacokinetics and clinical results obtained in an experimental model.
AB  - Tolfenamic acid (TA) was tested in two studies to investigate its value in
      controlling ocular inflammation in the dog. First, TA was assayed within primary
      and secondary aqueous humour (AH) and in plasma 0, 4 and 24 hours after a 4 mg/kg
      subcutaneous injection. Secondly, an experimental ocular surgery model was set up
      in 10 dogs-five receiving TA two hours before surgery and five left untreated. TA
      was shown to diffuse into AH, reaching lower levels than in plasma: 1:126 ratio
      in primary AH and 1:43 in secondary AH. In the model, TA-treated dogs versus
      untreated dogs showed a significant reduction of miosis (P < 0.05) and a clear
      trend to a reduced ocular discharge and corneal oedema (P = 0.06). Prostaglandin
      E2 (PGE2) levels increased significantly less in AH after TA treatment (P <
      0.05). These results show that TA, even if the whole concentration measured in AH
      is lower than in plasma, is able to limit the synthesis of the inflammatory
      mediator PGE2 in AH and to control ocular inflammatory symptoms induced by
      corneal surgery.

PMID- 8872938
TI  - Treatment of acquired myasthenia gravis associated with thymoma in two dogs.
AB  - Two cases of myasthenia gravis associated with thymoma are reported. Both were
      female German shepherd dogs and the thymoma was surgically resected. Aspiration
      pneumonia secondary to persistent megaoesophagus was a complication in both
      cases. The myasthenia gravis did not resolve, but there was a more satisfactory
      control of clinical signs with anticholinesterase treatment. Corticosteroid
      therapy was used in one case, but the resulting polydipsia increased the
      incidence of regurgitation, resulting in recurrent episodes of aspiration
      pneumonia.

PMID- 8872939
TI  - Methylmethacrylate and bone screw repair of seventh lumbar vertebral fracture
      luxations in dogs.
AB  - Fracture-luxations of the seventh lumbar vertebrae in two large dogs were
      stabilised with bone screws and methylmethacrylate. Screws inserted bilaterally
      into the bodies of the lumbar vertebrae and ilial wings were left protruding by
      about 2 cm, and embedded in methylmethacrylate bone cement. Implant failure
      occurred in one dog six days after surgery, necessitating a revision of the
      fixation. Fracture healing and return of normal ambulation occurred in both dogs.
      Implants were removed in one dog because of screw loosening and discomfort.

PMID- 8872940
TI  - Diagnosis of right coronary artery to right atrial fistula in a dog using two
      dimensional echocardiography.
AB  - A five-year-old boxer dog developed cardiac murmurs, complete heart block and
      cardiomegaly associated with vegetative bacterial endocarditis. Using two
      dimensional echocardiography, vegetative lesions of the aortic valves and
      extension of the vegetations into the proximal right coronary artery and adjacent
      atrial septum were identified. The vegetation within the atrial septum appeared
      as a cavitated mass which protruded into the right atrium. Fistulae within the
      atrial septal vegetation permitting communication between the coronary artery and
      right atrium were observed with colour Doppler echocardiography. The dog died
      despite medical treatment. Post mortem examination confirmed the
      echocardiographic findings. Vegetative endocarditis with invasion into the right
      coronary artery and atrial septum producing fistulae and communication with the
      right atrium has not been reported previously in dogs. Doppler echocardiography
      proved useful in demonstrating the abnormal anatomy, intraluminal fistular blood
      flow and its communication with the right atrium.

PMID- 8872941
TI  - What is your diagnosis?

PMID- 8872942
TI  - Sperm granuloma in the dog: complication of vasectomy.

PMID- 8872943
TI  - Reproductive disorders in 10 domestic male cats.
AB  - This study describes 10 tomcats with different reproductive disorders. Two of the
      cats had abnormal sex chromosomes; one was a tortoiseshell and white Cornish rex,
      while the other was a brown Burmese. The other eight cats were diagnosed as
      having testicular hypoplasia, diphallos in combination with unilateral
      cryptorchidism, a persistent penile frenulum, retrograde ejaculation, temporary
      oligozoospermia, teratozoospermia, azoospermia and congenital poor libido. For
      the cat with a persistent penile frenulum, and the cat with a temporary
      oligozoospermia, the prognosis for successful reproduction was considered
      favourable. By contrast it was considered unlikely that the cats with chromosomal
      abnormalities, testicular hypoplasia, diphallos, retrograde ejaculation,
      teratozoospermia and azoospermia would be able to produce offspring.

PMID- 8872944
TI  - The problem of inherited diseases. 3: Haemophilia in the German Shepherd.

PMID- 8872945
TI  - Primary renal abnormalities in hereditary hypertension.

PMID- 8872946
TI  - Polymorphisms of the renin-angiotensin system genes in progressive renal
      diseases.

PMID- 8872948
TI  - Expression of the 14 kDa galactose-binding protein, galectin-1, on human tubular
      epithelial cells.
AB  - By reverse phase PCR and Northern blotting, RNA of the 14 kDa galactose-binding
      protein (galectin-1) could be identified in primary cultures of human tubular
      epithelial cells. To assess protein synthesis and the possible function of
      galectin-1 on TEC, the cellular proteins were biosyntheticically labeled with
      [34S]-methionine and absorbed to immobilized laminin. Multiple radiolabeled
      proteins were eluted, a strong band in the area of 14 kDa was seen, coinciding
      with the galectin-1 band as identified by Western blotting. Surface expression of
      galectin-1 was seen by cytofluorometry with two different polyclonal antibodies
      to galectin-1. These data are in line with the finding that tubular epithelial
      cells adhere to laminin, partly in a Ca(2+)-independent manner.

PMID- 8872947
TI  - Insulin and angiotensin II are additive in stimulating TGF-beta 1 and matrix
      mRNAs in mesangial cells.
AB  - Angiotensin II (Ang II) and insulin are implicated in the mesangial cell
      hypertrophy and excessive accumulation of mesangial matrix seen in
      glomerulosclerosis. Therefore, the effects of Ang II with and without insulin on
      mRNA levels of several important extracellular matrix genes and transforming
      growth factor beta-1 (TGF-beta 1) were examined. Ang II alone (1 microM) added to
      quiescent, murine mesangial cells in serum-free, insulin-free media slightly but
      not significantly increased TGF-beta 1, fibronectin, collagen I, collagen IV and
      laminin message levels. The slight elevations in message expression were reversed
      by losartan, suggesting that these modest effects are mediated by the AT-1
      receptor. Ang II alone also had no significant effects on TGF-beta 1 and
      extracellular matrix message levels in quiescent rat mesangial cells. In
      contrast, significant increases in mRNA for collagen 1 (6-fold), collagen IV (4
      fold), fibronectin 1 (4-fold) and TGF-beta 1 (2-fold) were seen with insulin
      alone (10(-6)M) in rat mesangial cells, and a dose-response effect could be
      demonstrated for insulin (10(-9) to 10(-6)M). Ang II plus insulin further
      significantly increased collagen I (9-fold), collagen IV (9-fold), fibronectin 1
      (5-fold) and TGF-beta 1 (3-fold) message expression. These effects were partially
      reversed in the presence of losartan. The Northern analyses were supported by
      measurements of active and total TGF-beta 1 activity (pg/ml/ 5 x 10(6) cells):
      1145 +/- 76 and 1960 +/- 199, serum free control; 1121 +/- 92 and 1932 +/- 214,
      Ang II (10(-6)M); 4589 +/- 103 (P < 0.001 vs. control) and 11071 +/- 1952 (P <
      0.01 vs. control), insulin (10(-6)M); and 6881 +/- 183 (P < 0.001 vs. control)
      and 16626 +/- 1435 (P < 0.01 vs. control), insulin plus Ang II. These results
      suggest that insulin, itself, significantly increases TGF-beta 1 and
      extracellular matrix gene expression in rat mesangial cells. Ang II alone has
      modest effects, while Ang II and insulin have additive effects. To explain the
      mechanism of these additive effects, we investigated the action of Ang II on
      insulin signaling and the effect of insulin on Ang II AT1 receptor mRNA
      expression. Ang II did not enhance insulin-induced insulin receptor substrate-1
      (IRS-1) phosporylation or phosphatidylinositol3 (PI-3) kinase activity, but did
      enhance insulin-induced mitogen activated protein (MAP) kinase activity. Insulin
      increased message levels of AT1 receptor by twofold. These results suggest that
      enhancement of MAP kinase activity and AT1 receptor regulation by insulin may
      contribute to the additive effects of insulin and Ang II in mesangial cells.

PMID- 8872950
TI  - Biphasic glomerular hypertrophy in rats administered puromycin aminonucleoside.
AB  - Recent evidence suggests that glomerular hypertrophy is a key event in the
      development of focal and segmental glomerulosclerosis and hyalinosis (FSGS) in
      humans and in many experimental models of FSGS. The initial aim of the present
      study was to determine if glomerular hypertrophy occurs in a puromycin
      aminonucleoside (PAN) model of FSGS, previously considered not to involve
      glomerular hypertrophy. Upon identifying significant glomerular hypertrophy, our
      second aim was to determine the contribution of glomerular capillary growth to
      this hypertrophy. Female Sprague-Dawley rats (approximately 200 g) were
      administered either PAN (2 mg/100 g body wt) subcutaneously, or an equivalent
      volume of 0.9% saline at weeks 0, 1, 2, 4, 6, 8 and 10. Tissue was analyzed at
      weeks 7 and 13. Unbiased stereological methods were used to estimate a range of
      glomerular parameters. Mean glomerular tuft volume in PAN-treated rats was 48%
      greater than in saline-treated rats at seven weeks, and 63% greater at 13 weeks.
      Similar results were found for mean renal corpuscle volume. FSGS was absent at
      seven weeks and minor at 13 weeks. Two-way analysis of variance indicated:
      significant effects (P < 0.05 at least) of PAN on capillary length per
      glomerulus, capillary surface area per glomerulus, capillary diameter and length
      of capillaries per unit volume of glomerulus; and significant effects of time on
      capillary diameter, capillary length per unit volume of glomerulus and capillary
      surface area per unit volume of glomerulus. The mean length of capillaries per
      glomerulus was 45% greater in PAN-treated rats at week 7 and 22% greater in PAN
      treated rats at week 13. Taken together, these results indicate a biphasic
      pattern of glomerular hypertrophy in this model. In the first phase (to 7 weeks),
      an increase in capillary length contributes to glomerular hypertrophy. In the
      second phase (7 to 13 weeks), the continued glomerular enlargement appears more
      likely to be due to an increase in capillary diameter and/or mesangial matrix
      expansion.

PMID- 8872951
TI  - Role of endothelin in the pathophysiology of renal ischemia-reperfusion in normal
      rabbits.
AB  - The present study addressed the acute effects of endothelin-1 on renal function
      and neutrophils accumulation in the setting of in vivo severe (60 min) acute
      ischemia/reperfusion. Ischemia/reperfusion decreased renal functional parameters
      and increased renal neutrophil accumulation and medullary congestion. All these
      parameters markedly improved with the intrarenal administration of anti
      endothelin-1 antiserum. Comparatively, the intrarenal infusion of endothelin-1
      decreased renal function and increased neutrophil accumulation. Abnormalities in
      renal histology were, however, less pronounced than with ischemia/ reperfusion.
      In experiments using rabbit isolated perfused kidneys, endothelin-1 induced the
      accumulation of labeled neutrophils. This accumulation was similar to that
      observed in kidneys obtained after 60 minutes of ischemia plus 60 minutes of
      reperfusion. Both endothelin and ischemia/ reperfusion effects were counteracted
      by an anti-endothelin antibody. In further in vitro studies, we found that
      endothelin-1-induced the expression of the CD18 antigens on the neutrophil
      surface. In subsequent experiments based on this effect of ET-1 on CD18 antigens,
      a blockade of both ischemia/reperfusion-induced and endothelin-1-induced
      neutrophil accumulation was obtained by infusion an anti-CD18 antibody. In
      conclusion, our experiments disclosed the critical role of endothelin-1 as a
      major promoter of early neutrophil accumulation after ischemia/reperfusion, which
      occurred through an integrin-mediated mechanism.

PMID- 8872952
TI  - Early defect in branching morphogenesis of the ureteric bud in induced nephron
      deficit.
AB  - Development of the metanephric kidney during embryogenesis can be altered both in
      vivo and in vitro by exposure to gentamicin, which may lead to oligonephronia. To
      study the role of the ureteric bud in nephron deficit genesis, we used
      metanephros organ cultures exposed to gentamicin as a model of impaired
      nephrogenesis. Ultrastructural localization of the antibiotic showed that by
      eight hours it was already present within the epithelial cells of the ureteric
      bud and in its growing ends, and also trapped in the adjacent blastema. Using
      confocal microscopy and image analysis, we devised a quantitative approach to
      analyze the branching pattern of the ureteric bud, and showed that by 24 hours of
      culture, despite no change of explants growth, gentamicin had significantly
      decreased the number of branching points. This effect involved the early
      branching events and was limited to end buds that had no nephron anlagen nearby.
      Our findings indicate that impaired branching morphogenesis of the ureteric bud
      is the likely event of gentamicin-induced nephron deficit.

PMID- 8872953
TI  - Myoglobin inhibits proliferation of cultured human proximal tubular (HK-2) cells.
AB  - Following nephrotoxic injury, renal repair is dependent on tubular regeneration.
      In the case of myoglobinuric acute renal failure (ARF), persistence of myoglobin
      within tubular cells, or sublethal injury sustained at the height of exposure to
      it, might retard this process. To test this hypothesis, a human proximal tubular
      cell line (HK-2) was cultured for 24 hours in the absence or presence of
      clinically relevant myoglobin concentrations (0.5, 1, 2, 4 mg/ml). Immediately
      following myoglobin removal, lethal cell injury (vital dye uptake), lipid
      peroxidation, and DNA damage (alkaline unwinding assay) were assessed. The extent
      of cell proliferation was estimated over the next four days by a tetrazolium
      based (MTT) assay and by determining total intracellular LDH. Myoglobin's effects
      on protein and DNA synthesis were also assessed (35S-methionine and
      bromodeoxyuridine incorporation, respectively). Myoglobin induced dose-dependent
      lipid peroxidation (malondialdehyde generation) and cell death (up to 80% vital
      dye uptake with the 4 mg/ml challenge). Although 1 mg/ml myoglobin caused no cell
      death, it induced nearly complete growth arrest. This lasted for approximately
      three days following myoglobin removal from the media. Neither of two control
      proteins (albumin; lysozyme) nor a second nephrotoxin (gentamicin; 1 mg/ml)
      reproduced this effect. The 1 mg/ml myoglobin challenge caused an 80 to 90%
      depression in protein and DNA synthesis. It also induced significant DNA damage,
      as assessed by the alkaline unwinding assay (P < 0.01). Iron chelation therapy
      (deferoxamine) mitigated myoglobin-induced cell killing. However, its addition
      following myoglobin loading worsened HK-2 outgrowth by exerting a direct anti
      proliferative effect. These results indicate that: (1) sublethal myoglobin
      toxicity can induce transient proximal tubular cell growth arrest, potentially
      slowing recovery from ARF; (2) this effect correlates with, and could result
      from, heme-induced DNA damage and a blockade in DNA/protein synthesis; and (3)
      deferoxamine can inhibit proximal tubular cell proliferation. This possibility
      needs to be considered in designing clinical trials with DFO for
      myohemoglobinuric ARF.

PMID- 8872954
TI  - Phosphorylation of cAMP responsive element binding protein after treatment of
      mesangial cells with high glucose plus TGF beta or PMA.
AB  - We recently showed that mesangial cells treated with high glucose plus TGF beta
      or PMA demonstrated activation of a cAMP-response element (CRE) located in the 5'
      flanking region of the fibronectin gene. Gel shift mobility assays with a CRE
      oligonucleotide revealed multiple complexes that did not change in mobility or
      abundance under conditions of high glucose plus TGF beta or PMA. Here we show
      that treatment with cycloheximide to inhibit protein synthesis also did not
      change the DNA/protein complexes. These observations led us to conclude that post
      translational modification of transcription factors may be responsible for the
      activation of the fibronectin gene observed under our experimental conditions. We
      identified the proteins complexed to CRE as CRE binding protein (CREB) and
      activating factor 1 (ATF1). This was accomplished by supershift assays and
      immunoblots. Two hours of high glucose plus TGF beta or 30 minutes of PMA caused
      a twofold elevation in phosphorylated CREB. Neither high glucose nor TGF beta
      alone caused phosphorylation of CREB. ATF-1 was not phosphorylated. We also show
      that high glucose plus TGF beta and PMA activated protein kinase C alpha;
      however, none of the agents tested stimulated intracellular cAMP levels,
      indicating that phosphorylation of CREB was independent of protein kinase A
      activation. These results demonstrate cross-talk between the protein kinase C and
      protein kinase A pathways in that agents which activate the protein kinase C
      pathway can stimulate phosphorylation of proteins that commonly serve as
      substrates for protein kinase A.

PMID- 8872955
TI  - Epidemiology of acute renal failure: a prospective, multicenter, community-based
      study. Madrid Acute Renal Failure Study Group.
AB  - There are very limited data on overall epidemiology of ARF. It is crucial to know
      the incidence, etiology and clinical feature of ARF to promote prevention
      strategies and to implement adequate resources for the management of this entity.
      During a nine month period, a collaborative prospective protocol with 98
      variables was developed to assess all ARF episodes encountered in the 13 tertiary
      care hospitals in Madrid, Spain (covering 4.2 million people of over 14 years of
      age). ARF was considered when a sudden rise in serum creatinine concentration
      (SCr) to more than 177 mumol/liter was found in patients with normal renal
      function, or when the sudden rise (50% or more) was observed in patients with
      previous mild-to-moderate chronic renal failure (SCr < 264 mumol/liter). Of the
      748 cases of ARF studied, 665 episodes presented in inhabitants from the Madrid
      area. This gives an overall incidence of ARF of 209 cases per million population
      (p.m.p.; 95% CJ 195 to 223). The incidence of acute tubular necrosis (ATN) was 88
      cases p.m.p. (95% CI 79 to 97), prerenal ARF 46 p.m.p (95% CI 40 to 52), acute
      onset chronic ARF 29 p.m.p. (95% CI 24 to 34), and obstructive ARF 23 p.m.p. (95%
      CI 19 to 27). The mean age was 63 +/- 17 years. The most frequent causes of ARF
      were ATN (45%), prerenal (21%), acute-onset chronic renal failure (12.7%) and
      obstructive ARF (10%). Renal function was normal at admission in 48% of patients
      who later developed ARF. Mortality (45%) was much higher than that of the other
      patients admitted (5.4%, P < 0.001). This real outcome correlated extremely well
      with the expected outcome calculated through out the severity index of ARF (SI)
      0.433 +/- 0.246 (mean +/- SD). In 187 cases, mortality was attributed to
      underlying disease, thus corrected mortality due to ARF was 26.7%. Dialysis was
      required in 36% of patients, and was associated with a significantly higher SI of
      ARF (0.57 +/- 0.23 vs. 0.35 +/- 0.19, P < 0.001) and mortality (65.9 vs. 33.2%, P
      < 0.001). Mortality in patients hemodialyzed with biocompatible synthetic
      membranes (N = 50) was similar to that observed with cellulosic ones (N = 84; 66%
      vs. 59.5%, NS). Mortality was higher in patients with coma, assisted respiration,
      hypotension, jaundice (all P < 0.001) and oliguria (P < 0.02). This study gives,
      for the first time, the incidence of all forms of ARF in a developed country. ARF
      is iatrogenically induced at a high rate by modern medicine. Prevention
      strategies, particularly in the perioperative period, are needed to decrease its
      impact.

PMID- 8872956
TI  - Expression of betaine transporter mRNA: its unique localization and rapid
      regulation in rat kidney.
AB  - Betaine is a major compatible osmolyte in the renal medulla. It is taken up into
      cells via the betaine gamma-amino-n-butyric acid transporter (BGT-1). We
      investigated the localization of BGT-1 mRNA and its acute regulation by NaCl and
      furosemide administration. In situ hybridization revealed that BGT-1 mRNA is
      predominantly present in the outer medulla and papilla. Less intense signals were
      seen in the inner medulla and no signals were found in the cortex. Microscopic
      examination suggested that intense signals were present in the medullary thick
      ascending limbs of Henle's loop (MTAL) and the inner medullary collecting ducts
      (IMCD). A reverse transcription and polymerase chain reaction assay of individual
      microdissected segments along the nephron confirmed its localization.
      Intraperitoneal administration of NaCl rapidly increased the signal in the MTAL,
      and furosemide prevented the increase in BGT-1 mRNA by NaCl loading. In contrast,
      BGT-1 mRNA in the IMCD is less sensitive to these kinds of acute regulation.
      These results suggest that BGT-1 expression in the MTAL is rapidly regulated in
      response to the magnitude of NaCl absorption, as suggested for the expression of
      Na+/myo-inositol cotransporter.

PMID- 8872957
TI  - Potassium depletion modulates aldose reductase mRNA in rat renal inner medulla.
AB  - The organic osmolytes present in renal inner medullary cells balance the
      extracellular hyperosmolality and protect the cell against the effects of high
      salts and urea. We previously demonstrated that a renal concentrating defect due
      to potassium depletion was associated with a decrease in organic osmolytes
      including sorbitol. However, we could not determine whether a reduction in
      medullary organic osmolyte would be cause or effect of urine concentration defect
      associated with potassium depletion. We focused on the synthesis of sorbitol
      catalyzed by the enzyme, aldose reductase. To clarify whether the treatment of
      potassium depletion would affect aldose reductase when extracellular tonicity,
      and medullary sodium or potassium was maintained at the level of control rats, we
      administered a hypertonic solution of NaCl or KCl to potassium-depleted rats and
      evaluated aldose reductase enzymatic activity and mRNA abundance as well as the
      medullary contents of organic osmolytes. Either infusion significantly reduced
      tissue sodium content in potassium-depleted rats. With KCl infusion protocol but
      not that of NaCl, sorbitol as well as aldose reductase mRNA abundance increased
      to the control level. Medullary contents of other organic osmolytes exhibited a
      pattern similar to sorbitol. Data suggested that aldose reductase mRNA abundance
      was reduced in potassium depletion irrespective of medullary sodium content. A
      decrease in sorbitol level may precede a urinary concentrating defect. Our
      finding constitutes the first demonstration of the relationship between a
      potassium deficiency and the abundance of aldose reductase mRNA, an
      osmoregulatory protein in the kidney.

PMID- 8872958
TI  - Matrix metalloproteinases and TIMPS in cultured C57BL/6J-cpk kidney tubules.
AB  - Restructuring of basement membranes is a hallmark of the pathology of renal
      cystic disorders. Here, we present findings consistent with the view that
      basement membrane degradation by matrix metallo-proteinases (MMPs) may contribute
      to abnormal basement membrane structure in polycystic kidney disease. Cells from
      cystic kidney tubules embedded in collagen gels appeared to migrate through the
      gel. This migration through collagen indicated that these cells could degrade the
      matrix. To examine this activity, we cultured cystic kidney tubules derived from
      the C57BL/6J cpk/cpk mouse, a hereditary model of polycystic kidney disease, and
      assayed conditioned medium for the presence of MMPs and tissue inhibitors of
      metalloproteinases (TIMPs). The conditioned medium from the cystic tubules
      contained higher than normal levels of MMP-9, MMP-2, and MMP-3 as well as TIMP-1
      and TIMP-2. A 101 kDa protease was present equally in cystic and control cultures
      and although inhibited by EDTA, it was not inhibited by TIMPs, nor activated by
      the mercurial compound APMA. These data suggest that cystic kidney tubules
      synthesize and secrete high levels of MMPs which may then participate in the
      restructuring of the tubular basement membrane.

PMID- 8872959
TI  - Differential cytoprotection by glycine against oxidant damage to proximal tubule
      cells.
AB  - Tert-butyl hydroperoxide (tBHP) injured freshly isolated proximal tubules in an
      Fe-dependent fashion that was ameliorated by a lipophilic antioxidant, diphenyl-p
      phenylenediamine (DPPD), but was only minimally affected by glycine. Menadione
      induced injury was Fe-independent and was unaffected by DPPD, but was strongly
      blocked by glycine. Fe was highly toxic when intracellular loading was
      facilitated by concomitant treatment with hydroxyquinoline (HQ). This toxicity
      was blocked by DPPD or chelating the Fe, but not by glycine. All of the lesions
      were characterized by severe depletion of glutathione and other soluble thiols.
      Menadione induced large increases in protein associated with the Triton-insoluble
      cytoskeleton and decreases in protein thiol content, consistent with extensive
      cross linking, but did not increase thiobarbituric acid reactive substances
      (TBARS). tBHP and HQ + Fe had either no effect or only moderate, delayed effects
      on cytoskeletal proteins, but induced substantial increases of TBARS. Glycine did
      not the alter changes in cytoskeletal proteins, thiols, or TBARS produced by any
      of the agents. Protection against tBHP toxicity by deferoxamine and DPPD was
      accompanied by substantial suppression of TBARS accumulation. Superimposition of
      hypoxia during tBHP exposure reduced TBARS accumulation and restored
      cytoprotective activity to glycine. Thus, in contrast to its consistently strong
      cytoprotection against a number of other insults, glycine is only variably
      cytoprotective against oxidant lesions in freshly isolated proximal tubules.
      Extensive oxidative crosslinking of proteins is compatible with maintenance of
      glycine cytoprotection against lethal membrane damage. Fe-induced injury to
      proximal tubules associated with lipid peroxidation as manifested by TBARS
      formation is a relatively glycine-insensitive insult.

PMID- 8872960
TI  - Cellular mechanisms of the age-related decrease in renal phosphate reabsorption.
AB  - The aging process in humans and in the rat is associated with an impairment in
      renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet.
      The purposes of the present study were to determine whether changes in the
      abundance of type II Na-Pi contransporter (NaPi-2) protein and/or mRNA play a
      role in the age-related decrease in Na-Pi cotransport activity, and to further
      determine the cellular mechanisms of impaired adaptation to a low Pi diet. In
      studies performed in 3- to 4-month-old young adult rats and 32-to 16-month-old
      aged rats we found that there was an age-related twofold decrease in proximal
      tubular apical brush border membrane (BBM) Na-Pi cotransport activity, which was
      associated with similar decreases in BBM NaPi-2 protein abundance and renal
      cortical NaPi-2 mRNA level. Immunohisto-chemistry showed lower NaPi-2 protein
      expression in the BBM of proximal tubules of superficial, midcortical, and
      juxtamedullary nephrons. We also found that in response to chronic (7 days)
      and/or acute (4 hr) feeding of a low Pi diet there were similar adaptive
      increases in BBM Na-Pi cotransport activity and BBM NaPi-2 protein abundance in
      both young and aged rats. However, BBM Na-Pi cotransport activity and BBM NaPi-2
      protein abundance were still significantly lower in aged rats, in spite of a
      significantly lower serum Pi concentration in aged rats. The results indicate
      that impaired expression of the type II renal Na-Pi cotransporter protein at the
      level of the apical BBM plays an important role in the age-related impairment in
      renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet.

PMID- 8872961
TI  - Role of chloride channels in afferent arteriolar constriction.
AB  - The effects of IAA-94, a chloride channel blocker and/or low chloride perfusate
      on afferent arteriolar (AA) constriction by angiotensin II (Ang II),
      norepinephrine (NE) and increasing pressure (80 to 160 mm Hg) were assessed using
      isolated perfused hydronephrotic kidneys. In the first series of experiments, Ang
      II (0.3 nM) constricted AAs by 33 +/- 3% (N = 5, P < 0.01). Subsequent addition
      of diltiazem (10 microM) restored the decrements in the AA diameters. In the
      presence of diltiazem (10 microM), increasing pressure did not constrict AAs. In
      the second series of experiments. elevation of pressure constricted AAs by 20 +/-
      2% (N = 7. P < 0.01). Subsequent addition of IAA-94 (30 microM) failed to alter
      the basal AA diameter and myogenic responsiveness. However, Ang II-induced AA
      constriction was abolished by IAA-94. In the third series of experiments,
      decreasing extracellular chloride exaggerated AA constriction by 0.1 nM of Ang II
      (from 13 +/- 2 to 20 +/- 3%, N = 6, P < 0.05). Similarly, low chloride perfusate
      enhanced NE (0.1 microM)-induced AA constriction (from 14 +/- 2 to 19 +/- 2%, N =
      6, P < 0.05). In contrast, myogenic responsiveness was not influenced by reducing
      chloride concentrations. The present data provide evidence that both Ang II and
      NE induce AA constriction by opening chloride channels and subsequent activation
      of voltage-dependent calcium channels, and suggest that the myogenic response is
      mediated by activating voltage-dependent calcium channels independently of
      chloride channels.

PMID- 8872962
TI  - Role of obstruction in autosomal dominant polycystic kidney disease in rats.
AB  - Kidney micropuncture and microdissection studies were carried out on heterozygous
      2- to 4-month-old female and male Han:SPRD rats with autosomal dominant
      polycystic kidney disease (ADPKD) and on normal controls, to determine whether
      cysts are obstructed. Pressures in proximal tubules and cysts were determined
      using a servo null device and were recorded before, during, and after
      intraluminal infusion of an isotonic equilibrium solution at 15 and 50 n1/min.
      Initial cyst pressures in nine cystic rats averaged 18.5 +/- 5.9 (SD) mm Hg, N =
      49, significantly (P < 0.01) higher than in normal proximal tubules in four
      control rats, 14.3 +/- 1.6 mm Hg, N = 36. Pressures in non-cystic tubules in
      cystic rats, 16.8 +/- 4.4 mm Hg, N = 25, were not significantly different from
      pressures in control kidneys or in cysts. When proximal tubules were microinfused
      at 15 nl/min in control rats, tubule pressure increased by 3.8 +/- 1.2 mm Hg, N =
      24. In cysts, the response was highly variable. Twenty out of 33 microinfused
      cysts (61%) showed responses similar to normal tubules and were considered to be
      nonobstructed; 13 (39%) showed large pressure increases upon microinfusion,
      sometimes to values over 100 mm Hg (obstructed cysts). Left kidney inulin
      clearance (in microliter/min. 100 g body wt) averaged 335 +/- 65 (N = 4) in
      control rats and 344 +/- 144 (N = 9) in cystic rats; at this early stage of the
      disease no decline in GFR was seen. Weights of cystic kidneys were twice those of
      normal animals. Microdissection and scanning electron microscopy revealed the
      presence of intraluminal casts and debris and constrictions between cysts that
      would impede fluid flow. We conclude that obstruction is a frequent, early event
      in PKD and, when present, promotes cyst enlargement. Since many cysts are not
      obstructed, we suggest that factors other than fixed obstruction initiate cyst
      formation.

PMID- 8872963
TI  - Down-regulation of hepatic LDL receptor expression in experimental nephrosis.
AB  - Nephrotic syndrome (NS) is invariably associated with elevation of plasma total
      and LDL cholesterol concentrations. The present study was carried out to test the
      hypothesis that nephrotic LDL hypercholesterolemia is, in part, due to acquired
      LDL receptor (LDLR) deficiency. To this end, hepatic LDLR mRNA (Northern blot
      analysis) and protein mass (Western blot analysis) were measured longitudinally
      before and during the course of puromycin-induced NS. In addition, the rate of
      LDLR gene transcription by isolated hepatic nuclei was determined using nuclear
      run-on assay. Hepatic LDLR mRNA remained virtually unchanged during the 30-day
      course of the study period. However, after an insignificant rise on day 5, LDLR
      protein mass gradually declined to a level which was significantly below the
      baseline values (P < 0.05 ANOVA). This was accompanied by a normal rate of LDLR
      mRNA synthesis excluding impaired gene transcription as a cause. The fall in
      hepatic LDLR protein was associated with a marked rise in plasma total and LDL
      cholesterol concentrations but no rise in hepatic tissue cholesterol
      concentration. The latter observation is indicative of impaired hepatic
      cholesterol uptake and provides functional evidence for the demonstrated acquired
      LDLR deficiency in the NS animals. Likewise, our findings elucidate the molecular
      basis of the previously reported impaired LDL clearance in NS. In conclusion,
      severe hypercholesterolemia in rats with experimental NS is associated with and
      perhaps, in part, is due to down-regulation of LDL receptor expression.

PMID- 8872964
TI  - Opposite, binary regulatory pathways involved in IL-1-mediated stromelysin gene
      expression in rat mesangial cells.
AB  - Glomerular mesangial cells express matrix metalloproteinase sromelysin in
      response to the proinflammatory cytokine IL-1 beta. The present study was
      conducted to identify intracellular machinery involved in this IL-1 action,
      especially focusing on the role of the TPA response element (TRE) located in the
      5'-flanking region of the stromelysin gene. Using transient transfection with a
      pTRE-LacZ reporter plasmid, we detected no obvious up-regulation of TRE activity
      in rat mesangial cells following the IL-1 stimulation. However, the basal
      activity of TRE was found to be essential to the stromelysin induction, since (i)
      mesangial cells stably expressing a transdominant negative mutant of c-Jun, which
      effectively suppressed both basal and inducible TRE activity, exhibited the
      blunted expression of stromelysin in response to IL-1 beta, whereas (ii)
      transfection with a c-fos antisense gene, which suppressed only the inducible TRE
      activity, did not affect the stromelysin induction. To seek cooperative pathways
      required for the IL-1 action, we next focused on protein kinases, the potential
      regulators of the stromelysin gene. Stimulation of mesangial cells with a protein
      kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), induced the
      stromelysin transcript without affecting TRE activity. Depletion of intracellular
      PKC by high-dose PMA or inhibition of PKC activity with calphostin C suppressed
      the stromelysin induction by IL-1 beta, suggesting the crucial contribution of a
      PKC-mediated, but TRE-independent pathway. In contrast, either cAMP inducer
      forskolin or dibutyryl cAMP suppressed the IL-1-mediated stromelysin expression.
      An inhibitor of cAMP-dependent protein kinase A (PKA), HA1004, enhanced the IL-1
      effect in a dose-dependent manner. Unexpectedly, the inhibitory action of PKA was
      not through cAMP response element (CRE) but through TRE, because (i) activation
      of CRE was not induced by IL-1 beta, and (ii) cAMP-mediated activation of PKA
      suppressed the basal TRE activity. These findings elucidated the unique, binary
      regulation of stromelysin by IL-1 beta; that is, IL-1 up-regulated the transcript
      via the PKC-dependent pathway under the cooperation with constitutively active
      TRE, and this stimulatory effect was in part counterbalanced by the IL-1
      inducible PKA which down-regulated the basal TRE activity.

PMID- 8872965
TI  - Serum total renin is increased before microalbuminuria in diabetes.
AB  - Serum prorenin is increased in patients with insulin dependent diabetes mellitus
      (IDDM) with microvascular complications. The present longitudinal study
      investigated whether increases in serum total renin concentration (TRC,
      active+prorenin) can predict the development of microalbuminuria in IDDM patients
      over a 10 year period. TRC and albumin excretion rates (AER) were determined in
      78 IDDM patients who were followed longitudinally for 10.4 +/- 0.2 (mean +/- SE)
      years. Twelve patients had progressively increasing albuminuria (progressors),
      and these were compared to 66 patients in whom albuminuria did not rise (non
      progressors). The two groups had similar duration of diabetes, age, follow-up,
      glycemic control and blood pressure at the start of the study. Serum TRC was
      increased in progressors [350 (1.1) mIU/liter, geometric mean (tolerance factor)]
      compared to non-progressors [189 (1.2)] after 5 to 10 years duration of diabetes,
      and continued to rise in this group, reaching a mean of 923 mIU/liter (normal
      range 131 to 170) after 20 years of diabetes. When serial measurements of TRC and
      AER were compared in individual progressors, a significant increase in TRC was
      apparent up to five years before the onset of microalbuminuria. Microalbuminuria
      in patients with IDDM is preceded by a substantial increase in serum TRC,
      suggesting that serum TRC may predict the subsequent development of incipient
      nephropathy.

PMID- 8872966
TI  - Glomerular up-regulation of EIIIA and V120 fibronectin isoforms in proliferative
      immune complex nephritis.
AB  - Fibronectin: (FNs) comprise a family of adhesive glycoproteins that are prominent
      components of mesangial extracellular matrix and accumulate during glomerular
      injury. By alternative splicing of an unique mRNA precursor, various FN isoforms
      can be originated. In rat, three regions of the molecule are involved: EIIIA,
      EIIIB and V. Because specific FN isoforms are expressed in embryogenesis and
      wound healing, conditions characterized by cell migration and adhesion, we
      examined the pattern of FN isoforms in the mild and severe phases of a
      progressive immune complex proliferative nephritis in rats. We constructed
      specific probes to analyze the splicing pattern of FN pre-mRNAs by ribonuclease
      protection assays. FN mRNAs containing EIIIA, EIIIB and V regions increased
      along, the progression of nephritis, though the increment of EIIIB-FN mRNA was
      modest. However, different regulation of all these isoforms was observed. The
      percentage of FN mRNA containing the EIIIA exon versus total FN increased with
      the severity of the disease, while the percentage of FN mRNA containing the EIIIB
      exon decreased. Relative V-FN mRNA expression versus total FN mRNA increased only
      in the severe phase. By means of specific antibodies we also studied the presence
      of EIIIA, EIIIB and V-FN proteins in the kidney. In the normal glomerutus, EIIIA
      FN protein was barely detectable in the mesangium, increasing in the mild phase
      of nephritis. In the severe phase of nephritis, increased EIIIA-FN was localized
      in the mesangium, in Bowman's capsule and in crescents. By contrast, EIIIB-FN
      protein in the glomerulus was absent even in the severe phase. V120-FN protein,
      an isoform that mediates the attachment of leukocytes through the VLA-4 integrin,
      was present in the mesangium and glomerular capillary loops in control animals,
      and increased in the severe phase of nephritis, coinciding with a strong
      leukocyte infiltration. In conclusion, our results show that during immune
      glomerular injury there were marked changes in the pattern of FN isoforms
      expression. Since those isoforms, particularly V120 isoform, are important in
      cell adhesion and migration, their up-regulation may facilitate the recruitment
      of cells into the injured glomeruli. The blockade of the interaction between V120
      FN and infiltrating leukocytes may represent a new approach to the treatment of
      nephritis.

PMID- 8872967
TI  - Immunoglobulin-A and the pathogenesis of schistosomal glomerulopathy.
AB  - Several observations suggest that the evolution of schistosomal glomerulopathy
      into clinically overt and progressive disease may involve pathogenetic mechanisms
      other than simple glomerular deposition of parasitic antigens. In a previous
      study, IgA was suggested to be a mediator of late glomerular lesions in this
      disease. This issue is further addressed in this work. The study includes 32
      patients with hepatosplenic schistosomiasis, of whom 16 had overt glomerular
      involvement, along with four control groups: (a) 15 healthy volunteers; (b) 15
      patients with simple intestinal mansoniasis; (c) 17 patients with non
      schistosomal chronic liver disease; and (d) 21 subjects with primary nephrotic
      syndrome not associated with schistosomiasis. Routine assessment was done for all
      subjects including confirmatory tests for schistosomal infection, liver and renal
      function tests, hepatitis viral markers and abdominal ultrasonography. The total
      serum concentrations of IgG, IgM, IgA were measured, as well as their respective
      circulating immune complexes, rheumatoid factors, anti-gliadin- and anti-DNA
      antibodies. Liver and renal biopsies were obtained from the relevant groups and
      studied by light microscopy. Renal biopsies were also examined by
      immunofluorescence. Patients with simple intestinal schistosomiasis had a
      significant increase in IgM antigliadin antibodies. Those complicated with
      hepatosplenic involvement also had a significant increase in the mean IgG anti
      gliadin antibodies, IgG rheumatoid factor and IgM anti-DNA activity. Cases
      further complicated by overt glomerular disease showed a distinct IgA
      predominance, mainly expressed in the serum anti-gliadin antibody pool and anti
      DNA activity. This profile was essentially similar to that observed in control
      cirrhotics. There was a significant increase in the frequency of IgA glomerular
      deposits in renal biopsies obtained from patients with overt schistosomal
      glomerulopathy, in contrast to control nephrotics. The deposits were mainly
      mesangial, but were also encountered in subendothelial, subepithelial and
      peritubular locations. Their frequency was significantly higher with more
      advanced lesions as seen by light microscopy. The relevance of these data is
      discussed, leading to the following conclusions: (a) serum IgA-anti-gliadin and 
      anti-DNA antibodies, and glomerular IgA deposits are markers of significant renal
      involvement in patients with hepatosplenic schistosomiasis. (b) IgA may be
      involved in the pathogenesis of advanced glomerular pathology when superimposed
      on parasite-induced lesions. (c) There is a significant increase in serum auto
      reactivity in hepatosplenic schistosomiasis, which may also have pathogentic
      implications. (d) Increased production by the inflammatory bowel lesions,
      impaired clearance by the fibrotic livers and probable switching of
      immunoglobulin synthesis are suggested to explain the observed IgA predominance
      in those who develop renal complications.

PMID- 8872968
TI  - Use of vancomycin in high-flux hemodialysis: experience with 130 courses of
      therapy.
AB  - Vancomycin is often administered to hemodialysis patients at long dosage
      intervals because its removal by hemodialysis is considered to be negligible. We
      and others, however, have demonstrated significant removal of vancomycin by high
      flux hemodialysis. This report describes our experience with 89 courses of
      vancomycin using a revised regimen with a loading dose followed by 500 mg doses
      after each dialysis treatment, and compares results with 41 courses using single
      weekly dosing. All patients were dialyzed with high-flux membranes using
      volumetric ultrafiltration and bicarbonate dialysate. Serum vancomycin levels
      were obtained two hours after completion of infusion (peak) and immediately prior
      to dialysis (trough) and were measured by Abbot TDx fluorescence polarization
      immunoassay. Duration of multiple-dose therapy was 11 +/- 8 days, with mean total
      dose 3.6 +/- 1.8 g. Initial doses of 20 mg/kg rapidly and reliably established
      therapeutic pre-dialysis serum levels (10 to 25 micrograms/ml). In patients
      treated with multiple dosing 431 pre-dialysis levels were obtained. The mean
      level was 15.9 +/- 5.7 micrograms/ml; 55 levels (13%) were less than 10
      micrograms/ml and 22 (5%) were above 25 micrograms/ml. In patients treated once
      weekly, 77% of levels were below 10 micrograms/ml by five days after
      administration, and 84% at one week. No patient developed demonstrable
      ototoxicity. Twenty-five patients were treated for > or = two weeks, five for >
      or = four weeks, and two for > five weeks, with no evidence of toxic
      accumulation. Mean peak level was 20.1 +/- 4.6 micrograms/ml, with a mean
      difference from preceding pre-dialysis level of 7.2 +/- 2.2 micrograms/ml. We
      conclude that in high-flux hemodialysis, a 20 mg/kg loading dose of vancomycin
      followed by 500 mg doses after each dialysis treatment achieves predictable,
      adequate and safe therapeutic levels, does not lead to unacceptably high peaks,
      and does not accumulate during long treatment courses. By contrast, once-weekly
      vancomycin dosing resulted in subtherapeutic serum levels after five to seven
      days, and should be abandoned in the high-flux setting.

PMID- 8872969
TI  - Subtherapeutic erythropoietin and insulin-like growth factor-1 correct the anemia
      of chronic renal failure in the mouse.
AB  - Chronic renal failure (CRF) is associated with a hyporegenerative anemia, which
      is caused primarily by inadequate production of erythropoietin (EPO) by the
      diseased kidneys and is responsive to exogenous EPO administration. Little is
      known about compensatory mechanisms that might supervene in anemia with low
      levels of EPO. Multiple investigations in vitro suggest an important role for
      insulin-like growth factor-1 (IGF-1) as well as EPO in erythropoiesis. Recently,
      both EPO and IGF-1 in vitro have been found to stimulate erythroid colony forming
      units in the mouse. However, no studies have examined the effect of IGF-1, singly
      and in combination with EPO, in CRF in vivo. This study examined mice with
      surgically-induced renal failure of six weeks duration that were treated for
      three weeks with the combination of subtherapeutic doses of both EPO and IGF-1.
      The single administration of each cytokine caused no significant change in
      hemoglobin in all CRF mice. In marked contrast the combined administration of the
      two cytokines produced a striking rise in hemoglobin, resulting in anemia
      correction in the majority of animals. The response to the combination therapy
      was comparable to the maximal response obtained with a single EPO dose (10 U) in
      a dose-finding study. Although the data are limited to utilizing one dose of each
      cytokine and one preparation of IGF-1, the large increase in hemoglobin observed
      with the combination therapy indicates that these two cytokines work in concert
      to stimulate erythroid precursors in CRF. In addition, untreated CRF mice showed
      markedly increased serum levels of low molecular weight binding proteins for IGF
      1, potentially reducing the bioavailability of IGF-1. These findings taken
      together suggest that the anemia of CRF may represent both an EPO and a
      functional IGF-1 deficient state.

PMID- 8872970
TI  - Renal involvement in von Hippel-Lindau disease.
AB  - Renal involvement in von Hippel-Lindau (VHL) disease has emerged as the most
      prevalent cause of death in this hereditary disorder. In a group of 43 VHL
      patients (23 unrelated families) with renal lesions we examined whether severity
      of renal disease is affected by parental inheritance and VHL subtype (1, without
      pheochromocytoma; 2, with pheochromocytoma). We also tested whether and how
      nephron-sparing surgery could be applied. Renal involvement comprised multiple
      cysts and bilateral and multifocal carcinomas (RCC) which were detected by
      screening in 38 patients, at 30.5 (14 to 62) years of age. The severity of the
      renal disease was similar in VHL type 1 (79% of the pedigrees) and 2 (21%). It
      was not influenced by the sex of the carrier. Twenty-nine patients were operated
      on at a mean age of 33.6 years: 21 patients (28 kidneys or 61% of all operated
      kidneys) underwent nephron-sparing surgery, 4 had complete ablation of involved
      kidneys and thus required dialysis, 3 had uninephrectomy and 1 had cyst
      fenestration. Vascular thrombosis was the most severe early complication. It
      occurred in 4 of 9 kidneys treated by ex vivo surgery. During a median follow-up
      of 29 months, local recurrence occurred in 5 of 21 (24%) patients treated by
      nephron-sparing surgery, whereas 2 developed metastasis. Chronic renal failure
      (creatinine > 120 mumol/liter) affected 11 patients; in 9 of them, it was due to
      sequelae of surgery. In conclusion, screening of RCC and nephron-sparing surgery
      are of value in VHL patients. However, indications of ex vivo surgery should be
      drastically restricted and renal sequelae are not uncommon. Renal followup is
      required because of the risk of recurrence.

PMID- 8872971
TI  - Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA
      nephropathy.
AB  - Twelve IgA nephropathy (IgAN) patients and 18 controls were immunized with novel
      protein antigens, cholera toxin subunit B (CTB) via the nasal route and keyhole
      limpet hemocyanin (KLH) subcutaneously. Antibody secreting cells and antibody
      response in body fluids were determined by ELISPOT assay and ELISA, respectively.
      Analysis of variance showed, in contrast to controls (P < 0.001), no CTB-specific
      IgA response in the nasal washes of patients with IgAN. Significantly lower
      numbers of CTB-specific antibody-secreting cells in peripheral blood (P < 0.001)
      and CTB-specific antibodies in plasma (P < 0.005) were found in IgAN, both
      restricted to the IgA1 subclass. The proportions of CTB-specific IgA1-secreting
      cells in bone marrow aspirates correlated significantly with the corresponding
      ratios in plasma, with significantly lower values (P < 0.005) in IgAN as compared
      to controls. These results support the existence of a "mucosa-bone marrow axis"
      in humans, but no dysregulation of this axis was found in IgAN. The deficient
      mucosal IgA immune response to CTB observed in this study after primary mucosal
      immunization indicates that patients with IgAN have a defective immune response
      when challenged intranasally. These patients may depend on more frequent and/or
      prolonged antigen encounter at mucosal sites before efficient mucosal immunity is
      established. Repeated seeding of antigen-specific cells to secondary lympoid
      organs could result secondarily in the relative hyperresponsiveness found in IgAN
      upon reactivation by parenteral immunization.

PMID- 8872972
TI  - An orally active ETA/ETB receptor antagonist ameliorates proteinuria and
      glomerular lesions in rats with proliferative nephritis.
AB  - The proliferation of mesangial cells and the extracellular matrix expansion
      constitute the most outstanding morphological aspects of the majority of
      progressive glomerular diseases. In vitro, endothelin-1 (ET-1) is mitogenic for
      mesangial cells and induces matrix protein synthesis. We studied the possible
      participation of ET-1 in the pathogenesis of renal damage in a normotensive model
      of proliferative nephritis. Coincidentally with maximal proteinuria and
      glomerular lesions, an increase was found in the glomerular mRNA expression of
      preproET-1 and the ETA receptor (10 and 6 times compared to controls,
      respectively), but not of the ETB receptor, and in ET-1 urinary excretion (217 +/
      33 vs. 84 +/- 4 pg ET-1/24 hr, N = 4 to 5, P < 0.05). By in situ hybridization,
      an increase in preproET-1 mRNA expression in glomerular endothelial, epithelial
      and mesangial cells, and in come tubular cells was observed. The administration
      of bosentan, an ETA/ETB receptor antagonist, had a beneficial effect on the
      evolution of nephritis preventing the appearance of intense proteinuria (76 +/-
      35 vs. 380 +/- 77 mg/24 hr, N = 4 to 5, P < 0.05), the morphological lesions and
      the renal function impairment (creatinine clearance 367 +/- 46 vs. 268 +/- 33
      microliters/min/100 g, N = 4 to 5). Simultaneously, there was a decrease in ET-1
      urinary excretion (88 +/- 14 vs. 217 +/- 33 pgET-1/24 hr, N = 4,5, P < 0.05) and
      in the renal preproET-1 mRNA expression. The mean systolic blood pressures
      remained in the normal range in all animals. These data indicate that ET-1
      participates in the pathogenesis of proteinuria and glomerular injury in a model
      of proliferative nephritis. The nonpeptidic orally active ETA/ETB receptor
      antagonists could be useful in the treatment of some human nephritis.

PMID- 8872973
TI  - Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal
      transplant recipients.
AB  - To delineate the pathogenesis of the reduction in hemoglobin occurring in renal
      transplant patients treated with angiotensin converting enzyme inhibitors (ACEI)
      and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was
      conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney
      transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and
      captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI,
      AZA metabolites, renal function parameters and hematological parameters including
      erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured
      and compared with 15 similar patients matched for transplant function and
      enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA
      metabolites did not differ significantly in the presence or absence of the ACEI.
      Enalaprilat levels also showed no significant difference between the two patient
      groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased
      significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8
      +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI
      treatment had been discontinued. Simultaneously numbers of reticulocytes and
      erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a
      peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3
      +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI
      related anemia in renal transplant recipients seems to be due to the
      erythropoietin-lowering effect of this group of drugs. A pharmacokinetic
      interaction between AZA and enalapril is not likely since plasma enalaprilat
      levels were independent of the immunosuppressive regimen and AZA metabolite
      levels were unchanged in the presence and absence of the ACEI. Several mechanisms
      by which angiotensin converting enzyme blockade may cause a decrease in
      circulating erythropoietin are discussed.

PMID- 8872974
TI  - Peritoneal transport characteristics with glucose polymer based dialysate.
AB  - Dialysate fluids containing glucose polymers as osmotic agent are different from
      the conventional solutions, because they are iso-osmotic to plasma and produce
      transcapillary ultrafiltration (TCUF) by colloid osmosis. To investigate the
      effects on fluid and solute kinetics, a comparison was made between a 7.5%
      glucose polymer based dialysate (icodextrin) and 1.36% and 3.86% glucose based
      dialysate in 10 stable CAPD patients. In each patient three standard peritoneal
      permeability analyses (SPA) were done with the osmotic agents and concentrations
      mentioned above. Dextran 70 was added to the glucose solutions to calculate fluid
      kinetics. In the glucose polymer SPAs fluid kinetics were calculated from the
      dilution and disappearance of dextrin. The TCUF rate with icodextrin was closer
      to that obtained with 3.86% glucose than to 1.36% glucose. Extrapolation of the
      fluid profiles revealed sustained ultrafiltration with icodextrin. TCUF increased
      linearly in time in the icodextrin tests, whereas a hyperbola best described the
      glucose profiles. The effective lymphatic absorption rate with icodextrin was
      similar to the glucose based solutions. Mass transfer area coefficients of low
      molecular weight solutes with icodextrin were also similar to the values obtained
      with glucose, as was D/P creatinine. A positive correlation was present between
      the MTAC creatinine and the TCUF rate with icodextrin (r = 0.66, P = 0.05), which
      was absent in the glucose SPAs. This suggests that in patients with a larger
      effective peritoneal surface area, more ultrafiltration can be achieved by
      glucose polymer solutions. Clearances of beta 2-microglobulin (beta 2m) were
      higher with icodextrin than with 3.86% glucose and 1.36% glucose dialysate (P <
      0.05). No differences were found for the larger serum proteins albumin, IgG and
      alpha 2-macroglobulin. Initial D/PNa-->was higher (0.96) with icodextrin than
      with the glucose based solutions (0.92), due to the higher Na+ concentration of
      icodextrin, and it remained unchanged during the dwell. In contrast, D/PNa+ of
      1.36% glucose increased during the dwell, whereas D/PNa+ decreased with 3.86%
      glucose until 60 minutes, followed by a subsequent increase. The ultrafiltration
      coefficient (UFC) of the total peritoneal membrane was assessed using 3.86%
      glucose (0.18 +/- 0.04 ml/min/mm Hg), and the UFC of the small pores was assessed
      using icodextrin (0.06 +/- 0.008 ml/min/mm Hg). The difference between these
      represented the UFC through the transcellular pores, which averaged 50.5% of the
      total UFC, but with a very wide range (0 to 85%). An inverse relation existed
      between the duration of CAPD treatment and the total ultrafiltration coefficient
      (r = -0.68, P < 0.04), which could be attributed to a lower UFC of the
      transcellular pores in long-term patients (r = -0.66, P < 0.05), but not to the
      UFC of the small pores (r = -0.48, NS). The TCUFRo-60 min through the
      transcellular pores correlated with the sodium gradient, corrected for diffusion,
      in the first hour of the dwell (r = 0.69, P < 0.04), indicating that both
      parameters indeed measure transcellular water transport. It can be concluded that
      the glucose polymer solution induced sustained ultrafiltration and had no effect
      on peritoneal membrane characteristics. In addition, the results of the present
      study support the hypothesis that the glucose polymer solutions exerts its
      osmotic pressure across intercellular pores with radii of about 40 A. This leads
      to increased clearances of low molecular weight proteins such as beta 2m that are
      transported through these pores without sieving of Na+. The latter, as found
      during 3.86% glucose dialysate, is probably caused by transcellular water
      transport. The transcellular water transport accounted for 50% of the total
      ultrafiltration with glucose based dialysis solutions. It was lower in long-term
      CAPD patients.

PMID- 8872975
TI  - Calciuric response to an acute acid load in healthy subjects and hypercalciuric
      calcium stone formers.
AB  - Excessive animal protein consumption is associated with a greater risk of
      occurrence of renal calcium stone, presumably because of the attendant endogenous
      acid production. Indeed, chronic acid load enhances urinary calcium excretion
      possibly through an increased bone calcium release. Because acute studies are
      best designed to elucidate the mechanism, renal or extra renal, underlying
      hypercalciuria in the setting of enhanced acid load, we examined the response of
      9 healthy adults (8 males, 1 female, aged 38 +/- 3 years, weight 67 +/- 2 kg) and
      34 hypercalciuric recurrent calcium stone formers (31 males, 3 females, aged 44
      +/- 2 years, weight 72 +/- 2 kg), without any associated disease, to an oral acid
      load (NH4Cl 2 mmol/kg body wt). After an overnight fast, each patient and control
      was studied during one one-hour period before and three two-hour periods after
      their intake of the acid load. An additional group of four time-control subjects
      (4 males, aged 33 +/- 2 years, weight 66 +/- 2 kg) was studied as the
      experimental groups except that they did not receive the acid load. On baseline,
      the three groups exhibited similar glomerular filtration rates, net acid
      excretions, and plasma calcium and magnesium concentrations. However, fasting
      urine calcium and magnesium excretions were higher in hypercalciuric calcium
      stone formers than in healthy control or time-control subjects. In time-control
      subjects, plasma acid base status, net acid excretion, filtered loads of calcium
      and magnesium, and urinary calcium and magnesium excretions remained unchanged
      all over the study. By contrast, after the oral acute acid load, net acid
      excretion increased and urinary pH decreased similarly in patient and control
      groups; glomerular filtration rate did not change, as well as plasma calcium and
      magnesium concentrations. Nevertheless, urinary calcium and magnesium excretions
      markedly increased, in both groups, independently of changes in tubular sodium
      handling and in plasma parathyroid hormone concentration. The increase in urinary
      calcium and magnesium excretions that occurred in the absence of any change in
      the filtered load of calcium and magnesium was therefore mediated by a decrease
      in tubular calcium and magnesium reabsorption, independent of PTH, but dependent
      on changes in net acid excretion. A positive linear relationship between urinary
      calcium and magnesium excretions suggested that the target tubular site for acid
      load was the thick ascending limb of Henle's loop. Finally, a negative linear
      relationship was demonstrated between the acid load-induced increase in urinary
      calcium excretion and fasting urinary calcium excretion; indeed, the lowest
      calciuric responses were observed in patients with the highest fasting urinary
      calcium excretion. Thus there was no additional effect of the acid load-induced
      inhibition on intrinsic defect in tubular calcium reabsorption which suggests
      that the tubular target site for acid load and the site of calcium transport
      defect in idiopathic hypercalciuria may be the same.

PMID- 8872976
TI  - Left ventricular abnormalities in children, adolescents and young adults with
      renal disease.
AB  - The cardiac abnormalities that complicate chronic renal failure and renal
      replacement therapy are not well characterized in young people. These
      abnormalities are becoming more important because successful renal
      transplantation has resulted in children with end-stage renal failure living
      longer. Echocardiographic abnormalities of cardiac function and structure were
      studied in children and young adults (< 27 years old) with chronic renal failure
      (CRF, N = 32), end-stage renal failure treated with chronic peritoneal dialysis
      (CPD, N = 10) or renal transplantation (N = 30) or controls (N = 60). Left
      ventricular mass indexed for height (LVM/Ht and LVM/Ht2.7) and body surface area
      (LVM/SA), fractional shortening, measurement of left ventricular diastolic
      function (peak E and A wave velocities and the EA ratio) and structural (such as
      valvular) abnormalities were determined by echocardiography. The median (and
      range) of LVM/Ht in the groups were control 51.8 (23.1 to 119.8), CRF 60.2 (22.2
      to 135.8), CPD 80.2 (14.5 to 100.9) and transplant group 97.8 (51.2 to 182.1)
      g/m. The increases in LVM/Ht, LVM/Ht2.7 and LVM/SA in the transplant group were
      significant (P < 0.01). The CRF group had significantly increased LVM/Ht2.7 and
      LVM/SA (P < 0.01). Systolic function was not significantly different between the
      groups. A significant correlation between creatinine and LVM indexed for height
      was found in the CRF group. Systolic or diastolic blood pressure could not be
      correlated with LVM indices in the transplant group. Changes in diastolic
      function were found (increased peak A wave velocity and decreased E/A ratios in
      the CRF and CPD groups, and increased peak E wave velocity in the transplant
      group). The study demonstrated that left ventricular hypertrophy is a frequent
      and often severe finding in children with chronic renal failure and those treated
      with renal replacement therapy. Factors other than hypertension and anaemia are
      important, and evidence was found for a link between serum creatinine and
      increased left ventricular mass prior to end-stage renal failure.

PMID- 8872977
TI  - Macrophage colony stimulating factor involvement in uremic patients.
AB  - The immunodeficiency of patients with chronic renal failure (CRF) is related to
      multiple and complex alterations of the cytokine network and of its target cells
      such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic
      activation of monocytic functions is recognized as a key factor in these
      immunological disorders. Since macrophage colony stimulating factor (M-CSF) is
      essential for the activation of several functions of monocytes and macrophages
      and their production of cytokines such as interleukin-1, interleukin-6, and tumor
      necrosis factor alpha, we investigated its involvement in patients with CRF. When
      measured by ELISA, M-CSF serum levels were significantly higher in patients with
      progressive CRF and those on hemodialysis (HD) and continuous ambulatory
      peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate
      with the degree of renal insufficiency and were probably related to complex
      alterations in its production and/or degradation by the specific M-CSF receptors
      of macrophages. In HD patients the M-CSF serum concentrations inversely
      correlated with the number of circulating lymphocytes and were significantly
      higher in anemic patients requiring treatment with erythropoietin. Our results
      suggest that M-CSF may play a role in altering the immune system in uremic
      patients by maintaining in the circulation and tissues permanently primed
      monocytes and/or macrophages that can then be triggered to an activated state by
      secondary stimuli such as endotoxins, complement components, other cytokines or
      contact with foreign surfaces.

PMID- 8872978
TI  - ESRD patient mortality with adjustment for comorbid conditions in Lombardy
      (Italy) versus the United States.
AB  - The present study evaluated end-stage renal disease (ESRD) patient survival in
      Lombardy, Italy, and the United States (U.S.) using data from two registries, the
      Lombardy Dialysis and Transplant Registry (RLDT) and the U.S. Renal Data System
      (USRDS), respectively. For this purpose, 4,196 white patients (2,900 from the
      USRDS Case Mix Severity Study and all 1296 from RLDT) who started renal
      replacement therapy in 1986 and 1987 were studied. Compared to Lombardy patients,
      those in the USA were significantly older (mean age 59.9 +/- 16.4 vs. 55.9 +/-
      14.7 years), had a lower proportion of males (53.7 vs. 62.1%), a greater
      proportion with diabetic nephropathy (29.9 vs. 9.7%) and a significantly greater
      proportion of patients with the recorded comorbid conditions (heart disease,
      peripheral vascular disease, cirrhosis, cachexia, malignancy). U.S. patients were
      less frequently treated with peritoneal dialysis (PD) by day 30 of ESRD (21.2 vs.
      30.7). Survival was compared in the Cox proportional hazard regression model,
      using age, sex, comorbid conditions and early modality of treatment as
      explanatory covariates. Overall, 48% of the 4196 patients died during the 48 to
      72 months follow-up to 12/31/91. Per 100 patient-years the gross death rate for
      USRDS patients was 28.7 compared to 13.0 of RLDT patients. The unadjusted death
      relative risk for RLDT was 0.439, that is, 56% lower death rate compared to USRDS
      patients. Age, sex, diabetic status, each of the recorded comorbid conditions and
      treatment modality were significantly related to survival and included in the
      model. The Cox cumulative survival adjusted for all these explanatory covariates
      survival was for U.S. patients 84.4% at one year, 67.0% at two years and 33.4% at
      five years, and for RLDT patients 88.3% at one year, 75.9% at two years and 45.9%
      at five years. The relative mortality risk (RR) for the patients treated in
      Lombardy adjusted for all the reported covariates was 29% lower than for US
      patients (RR = 0.71; P < 0.0001). This comparative risk varied significantly by
      age (P < 0.0001) and was 65 percent lower for Lombardy compared to U.S. patients
      in the age range 25 to 44 years (RR = 0.35) and about 20% lower for patients over
      age 65 years (RR = 0.80). This relative risk was mainly related to hemodialysis
      and was not statistically significant for PD patients. The observed lower
      mortality risk in Lombardy was less pronounced when adjusted for demographic and
      comorbid covariates, but was still large and therefore suggests the need for
      further studies regarding treatment related factors and unmeasured patient
      factors, particularly in hemodialysis patients.

PMID- 8872979
TI  - Detection of donor-specific hyporesponsiveness following late failure of human
      renal allografts.
AB  - Limiting dilution assays to measure the frequency of interleukin-2-secreting
      peripheral blood T cells were carried out in patients, whose renal allografts had
      failed due to acute rejection (9 patients) and in patients whose grafts failed
      more than two years after transplantation without any recent evidence of acute
      rejection. Using a modified form of the assay we demonstrate that nearly half of
      18 patients whose renal transplants had failed after more than two years have low
      or undetectable HTLp frequencies against donor, but not third-party DR antigens.
      No such difference was observed in any of the nine patients studied whose
      transplants were lost from early acute rejection. These results provide the first
      indication that, as in rodent models of transplantation, T cell unresponsiveness
      towards donor MHC antigens can occur following prolonged residence of an
      allograft in humans. Furthermore, the results suggest that chronic rejection may
      be driven by mechanisms other than direct allorecognition. The assay may be a
      valuable tool to study the evolution of donor-specific direct T cell
      alloresponsiveness in patients with well-functioning grafts.

PMID- 8872980
TI  - Renal function in high dose chemotherapy and autologous hematopoietic cell
      support treatment for breast cancer.
AB  - Autologous and allogeneic bone marrow grafting both require cytoreductive therapy
      but only the allogeneic procedure requires immunosuppressive agents. Allogeneic
      bone marrow transplantation has been reported to be associated with a high
      incidence of both renal failure and veno-occlusive disease (VOD) of the liver,
      the combination of which is associated with a high morbidity and mortality. There
      is less known about the frequency and severity of these complications in patients
      undergoing autologous bone marrow transplantation. In the present study renal,
      hepatic and other complications were examined in 232 patients with Stages II/III
      and IV breast cancer who were treated with high-dose chemotherapy and autologous
      hematopoietic cell support with either marrow or peripheral blood progenitor
      cells. The post-treatment severity of the renal dysfunction was classified as
      follows: Grade 0, normal renal function [< 25% decrement in glomerular filtration
      rate (GFR)]; Grade 1. mild renal dysfunction (> 25% decrement in GFR but < a
      twofold increase in serum creatinine); Grade 2, > twofold rise in serum
      creatinine but no need for dialysis; Grade 3 > than twofold rise in serum
      creatinine and need for dialysis. There were 102 patients (44%) who were
      classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal
      dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the
      232 patients (21%). This severe renal dysfunction of 21% compares with a
      previously reported 53% incidence of severe renal dysfunction for allogeneic bone
      marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or
      11 of 232 patients) in this autologous bone marrow transplant study as compared
      to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of
      allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades
      2 and 3) in the present autologous hematopoietic cell support study correlated
      most significantly with sepsis, liver and pulmonary dysfunction. The major fall
      in GFR occurred during chemotherapy but before hematopoietic cell support, thus
      primarily incriminating the cytoreductive therapy rather than the hematopoietic
      cell support. The only significant effect of different chemotherapy protocols
      was, at four weeks, the Taxol-treated group had a significantly lower creatinine
      clearance as compared to the BCNU treated group.

PMID- 8872981
TI  - Renal oxidant injury and oxidant response induced by mercury.
AB  - The role of oxidative stress in mercuric chloride (HgCl2)-induced nephrotoxicity
      is uncertain and controversial. We demonstrate that I.L.C-PK1 cells, exposed to
      HgCl2, generate massive amounts of hydrogen peroxide, the latter completely
      quenched by the hydrogen peroxide scavenger, pyruvate. HgCl2 exerts a dose
      dependent cytotoxicity which is attenuated by pyruvate and catalase. Cellular
      generation of hydrogen peroxide arises, at least in part, from mitochondria since
      mitochondrial rates of generation of hydrogen peroxide increase in response to
      HgCl2; HgCl2 also provokes a shift in absorbance spectra in rhodamine 123 loaded
      mitochondria and stimulates mitochondrial state 4 respiration. HgCl2, applied for
      one hour, impairs cellular vitality as demonstrated by the MTT assay, an assay
      dependent in part on mitochondrial function. HgCl2 impairs function in other
      organelles such as lysosomes that maintain a transmembrane proton gradient; these
      latter effects are partially attenuated by pyruvate. We complement these in vitro
      findings with in vivo evidence demonstrating that HgCl2 stimulates renal
      generation of hydrogen peroxide. The functional significance of such generation
      of hydrogen peroxide was evaluated in rats deficient in selenium and vitamin E, a
      nutrient deficiency that impairs the scavenging of hydrogen peroxide and promotes
      the toxicity of this oxidant. In these rats serum creatinine values were
      significantly higher on sequential days following the administration of HgCl2. To
      probe the renal response to oxidative stress induced by HgCl2, we examined
      hydrogen peroxide-scavenging enzymes and redox-sensitive genes. Catalase activity
      was unaltered whereas glutathione peroxidase activity was decreased, effects that
      may contribute to the net renal generation of hydrogen peroxide. The redox
      sensitive enzyme, heme oxygenase, was markedly up-regulated in the kidney in
      response to HgCl2. HgCl2 also induced members of the bcl family, bcl2 and bclx,
      genes that protect against apoptosis and oxidant injury. In another model of
      oxidant-induced renal injury, the glycerol model, bcl2 mRNA was not induced at 6
      and 24 hours after the administration of glycerol. In summary, we demonstrate
      that HgCl2 potently stimulates renal generation of hydrogen peroxide in vitro and
      in vivo and such generation of peroxide contributes to renal dysfunction in vitro
      and in vivo. We also demonstrate that in response to HgCl2, redox sensitive genes
      are expressed including heme oxygenase and members of the bcl family.

PMID- 8872982
TI  - GM-CSF secretion in primary cultures of normal and cancerous human renal cells.
AB  - Rates of secretion of granulocyte-macrophage colony stimulating factor (GM-CSF)
      were measured in 50 primary cell cultures derived from cancerous and normal human
      kidneys. Mean rates of GM-CSF secretion measured by TF-1 cell proliferation assay
      (N = 21) and by ELISA (N = 31) were 2.5 and 7.8 ng/10(6) cells/24 hr,
      respectively. There was no significant difference between the mean rates of GM
      CSF secretion by cancerous and normal renal cells. GM-CSF was also secreted by
      primary renal cell cultures grown in serum-free medium and by renal cell lines.
      GM-CSF mRNA was detected by RT-PCR in cultured renal cells, but not in
      undissociated kidney tissue. Rates of GM-CSF secretion were reduced up to 99%
      under conditions where the cellular density or substratum more closely resembled
      the in vivo environment. Some cultured human renal carcinoma cells (RCC) secreted
      GM-CSF at levels that occasionally overlapped the levels produced by the GM-CSF
      gene-modified human RCC vaccine now in phase I trial. The data indicate that GM
      CSF is not expressed in vivo, and that stable GM-CSF secretion is induced by the
      dissociation and culture of human renal cells.

PMID- 8872983
TI  - Isolation and characterization of luminal and basolateral plasma membrane
      vesicles from the medullary thick ascending loop of Henle.

PMID- 8872984
TI  - Urinary microscopy from the seventeenth century to the present day.

PMID- 8872985
TI  - The renal allograft biopsy.

PMID- 8872986
TI  - Rodent parvovirus infections.
AB  - Parvoviruses are among the most common infectious agents of laboratory rodents
      and major impediments to rodent-based research. The original prototypic rodent
      parvoviruses-minute virus of mice, rat virus, and H-1 virus-have recently been
      joined by biologically and antigenically distinct parvoviruses in mice, rats, and
      hamsters. Recognition of the increased diversity of rodent parvoviruses presents
      new challenges for determining the impact of parvovirus infection on research and
      for detecting, preventing, and eliminating infection. This review summarizes
      current knowledge about rodent parvoviruses and parvovirus infections,
      highlighting recent research on newly isolated virus strains.

PMID- 8872987
TI  - The effect of combined rotavirus and Escherichia coli infections in rabbits.
AB  - In rabbits, experimentally induced rotavirus infection results in soft feces
      only; thus it is unlikely that it is the sole cause of the severe, often fatal
      diarrhea of weanling rabbits with which it is associated. To determine whether
      rotavirus acts synergistically with another pathogen, New Zealand White rabbits
      (10 to 38 weeks old) were inoculated with rotavirus (L:ALA:84) and/or Escherichia
      coli 015:H-(RDEC-1) via orogastric tube. A single dose of high-titer (10(6)
      fluorescent focus-forming units) rotavirus was used, whereas E. coli was
      administered in various doses (10(2) to 10(9) CFU) to determine the titer of E.
      coli that induced only mild diarrhea but, when combined with rotavirus, resulted
      in diarrheal disease. Doses of E. coli > 10(6) CFU resulted in infection in
      almost all rabbits 10 to 16 weeks old, as detected by fecal shedding, regardless
      of whether rotavirus was inoculated simultaneously. However, inoculation of >
      10(6) CFU of E. coli, in conjunction with rotavirus, resulted in increased
      morbidity and mortality due to diarrheal disease compared with E. coli alone.
      Inoculation of rabbits 28 to 38 weeks old with similar doses of rotavirus and E.
      coli caused infection but failed to induce diarrhea, indicating that older
      rabbits were more resistant to the pathogenic effects of these two agents. A
      synergistic effect between rotavirus and E. coli occurred, causing more severe
      diarrheal disease in weanling rabbits than that resulting from either pathogen
      alone.

PMID- 8872988
TI  - Randomly amplified polymorphic DNA polymerase chain reaction assay for molecular
      epidemiologic investigation of Pasteurella pneumotropica in laboratory rodent
      colonies.
AB  - After an episode of clinical Pasteurella pneumotropica infection was diagnosed in
      a C57BL/6N mouse, a randomly amplified polymorphic DNA polymerase chain reaction
      assay (RAPD-PCR) was developed and used to genetically characterize and
      differentiate 52 field isolates and laboratory reference strains of P.
      pneumotropica and related bacteria. A survey of rodents in the facility recovered
      36 isolates of P. pneumotropica from 30 mice, six isolates from hamsters, and
      three isolates from rats during the follow-up investigation. Antibiograms and
      routine bacteriologic evaluations for morphologic and biochemical characteristics
      on selective media did not substantively aid in the differentiation of these
      isolates, but the RAPD-PCR revealed four strains of P. pneumotropica in the
      colony, two of which were confined to rats and hamsters. The RAPD-PCR
      unambiguously differentiated Heyl and Jawetz biotypes of P. pneumotropica
      recovered from mice, identified two additional genetic groups for rat and hamster
      isolates, and clearly distinguished P. pneumotropica from related bacteria. Most
      field isolates were genetically consistent with the Jawetz biotype of P.
      pneumotropica. The RAPD-PCR is a fast, sensitive, and efficient method for
      identifying genetic differences between strains of the P. pneumotropica complex
      and can contribute substantially in addressing the epidemiology, pathogenesis,
      and taxonomic classification of this common opportunistic pathogen.

PMID- 8872989
TI  - Establishment of an animal model for myoglobinuria by use of a myotoxin from
      Pseudechis australis (king brown snake) venom in mice.
AB  - A new laboratory animal model for studying the pathologic mechanisms of
      myoglobinuria in mice after envenomation with Pseudechis australis snake venom or
      its myotoxin has been established. The experimental mice (Swiss albino) had
      myoglobinuria 60 min after administration of the venom, as indicated by red or
      dark-brown urine. Light microscopic studies revealed myonecrosis of the locally
      injected soleus muscle 30 min after exposure to the myotoxin, followed by
      regeneration in 7 to 10 days. Electron microscopic studies of the soleus muscle
      revealed fragmentation and dissolution of the Z disk, followed by degeneration of
      the sarcomere. Light microscopy of the kidneys revealed numerous pigmented casts
      filling the lumen of the tubules; some tubules had features of acute tubular
      necrosis. Immunohistochemical localization of myoglobin by the immunoperoxidase
      method confirmed myoglobin casts in the renal tubules. Electron microscopy of the
      kidneys also revealed intratubular casts composed of markedly electron-dense
      material filling the lumen. These results indicate that rhabdomyolysis caused by
      the venom or toxin is followed by myoglobinuria, with renal manifestations in the
      form of myoglobin cast nephropathy and tubulopathy. This mouse model of
      experimental snake venom-induced myoglobinuria is an ideal model for
      investigating the entire sequence of myoglobinuria and related cast nephropathy.

PMID- 8872990
TI  - Dilated cardiomyopathy in turkeys: an animal model for the study of human heart
      failure.
AB  - Many animal models of heart failure developed to date do not mimic
      pathophysiologic changes recently described in the failing human myocardium. In
      human endstage heart failure, abnormalities in morphology, electromechanical
      coupling, and myocardial energetics have been described. However, studies of
      human myocardium are limited by lack of appropriate controls, the fact that all
      patients have endstage heart failure, and exposure of patients to different
      therapeutic regimens. In contrast to many animal models, the myopathic turkey
      heart (i.e., idiopathic dilated cardiomyopathy or furazolidone-induced
      cardiomyopathy) is similar to the myopathic human heart in terms of gross
      morphology, myocardial energetics, muscle physiology myofilament properties, Ca2+
      metabolism, and the beta-receptor-adenylyl cyclase signaling system.

PMID- 8872991
TI  - Evaluation of the chimpanzee breeding program at the Southwest Foundation for
      Biomedical Research.
AB  - The history of the chimpanzee (Pan troglodytes) breeding colony of the Southwest
      Foundation for Biomedical Research was evaluated over a 24-year period to
      determine age at conception, breeder rearing history, maternal competence, and
      infant rearing history. The records of 107 breeders and 268 live births were
      reviewed. Of the breeders with known rearing histories, 40 were wild-born (12
      male and 28 female), 16 were reared by their mothers for at least 1 month (8 male
      and 8 female), and 13 were removed from their mothers immediately after birth (2
      males and 11 females). The age of successful mating for males ranged from 7 to 32
      years and for females from 7 to 41 years, although the upper limit indicates the
      age of the population and not reproductive senescence. The mother's rearing
      history was related to her maternal competence, defined as caring for an infant
      for at least 1 month. Of the wild-born females, 82% (18/22) were competent
      mothers. For females that had been reared in captivity with their mothers for 1
      to 12 months, 71% (5/7) were competent. For females that had been removed from
      their mothers immediately and reared in a nursery by humans, only 14% (1/7) were
      competent. The rearing strategies have changed during the period under
      consideration. The number of infants reared by their mothers increased in the
      1980s, while the number of infants removed from their mothers immediately for
      experimental reasons decreased and dropped to zero in the 1990s. Information on
      the history of the breeding colony has been used to make management decisions and
      to determine the expectations of the Southwest Foundation chimpanzee breeding
      program.

PMID- 8872992
TI  - The origin of SL family mice.
AB  - The origin of SL family mice was studied by analyzing 100 microsatellite loci,
      the major histocompatibility complex, the Mx gene, murine leukemia provirus, and
      mammary tumor provirus. From the genetic profile of family members and their
      history, we assumed the existence of a proto-SL mouse, an ancestor of all SL
      family members. Many alleles were contributed to the proto-SL by the ancestors
      related to strains A2G and CF#1, and/or some wild mice. Among four existing
      family members, SL/Am and SL/Ni mice were almost identical and presumably closest
      to the proto-SL. The SL/Kh mouse was derived from a cross of the proto-SL and AKR
      mice, because SL/Kh mice inherited a considerable number of genes from AKR mice,
      the most outstanding of which were those of the provirus Emv-11 and Thy-1.1. The
      SL/QDj mice seemed to be a recombinant inbred strain between SL/Am and SL/Kh
      mice, because their alleles at all 100 microsatellite loci were shared by SL/Am
      or SL/Kh strains or both. All four SL family members shared the major
      histocompatibility complex haplotype q.

PMID- 8872993
TI  - New immunodeficient mouse strains bred by introducing beige and xid mutations
      into the KSN nude strain.
AB  - We introduced two mutant genes (beige or bg, which induces a deficiency of
      natural killer activity, and xid, which decreases the production of
      immunoglobulins) into KSN nude mice with high reproductive performance. At first
      we produced the KSN-bg/bg(nu/nu) (KSN-bg) and KSN-xid/xid(nu/nu) (KSN-xid)
      congenic strain by backcross (cross-intercross method). After we identified
      homozygosity at the biochemical locus and polymorphic microsatellite loci, we
      mated KSN-bg and KSN-xid mice, and selected the KSN-xid/xid;bg/bg(nu/nu) (KSN
      BNX) mice from the progeny. Furthermore we introduced the non-nude gene, which
      originated from CBA/N, into the KSN strain and produced KSN-nu/+ (KS) mice that
      have the same genetic background except for the nu locus. All strains had as high
      a reproductivity rate as the parental KSN mice. The KSN-xid and KSN-BNX mice had
      a reduced percentage of B220-positive cells in the spleen compared with KSN and
      KSN-bg mice, but they had increased percentages of Thy-1 and asialo GM1-positive
      cells. The serum immunoglobulin concentrations of BNX were as low as those of KSN
      xid mice. Both KSN-bg and KSN-BNX mice had deficient natural killer activity in
      the spleen, whereas KSN-xid mice had increased natural killer activity. Compared
      with nude mice, the growth of the human thyroid tumor cell line transplanted
      subcutaneously was enhanced in BNX mice. These KSN, KSN-bg, KSN-xid, KSN-BNX, and
      KS nice not only are of value for use in various fields as the hosts of xenograft
      but also are good models of the combination effect of multiple immunodeficient
      genes.

PMID- 8872994
TI  - Effect of in vivo administration of anesthetics on GABAA receptor function.
AB  - In research involving tissue derived from animals, the use of anesthesia before
      sacrifice is recommended by the American Veterinary Medical Association and is
      strongly encouraged by university committees on the use of animals in research.
      In this study, the effects of anesthesia on the modulation of the GABAA receptor
      complex by ethanol, a benzodiazepine, and a barbiturate were determined. In vivo
      administration of the anesthetic methoxyflurane and CO2 before sacrifice resulted
      in a decrease in Cl- flux in mouse brain microsacs. These treatments also
      resulted in the loss of the ability of the GABAA receptor modulatory agents
      flunitrazepam and ethanol to enhance the Cl- flux in this assay system.

PMID- 8872995
TI  - Effects of two injectable anesthetic agents on coagulation assays in the rat.
AB  - The rat is commonly used as an animal model to test the efficacy of new
      anticoagulant and antithrombotic drugs. Many of the protocols require the use of
      anesthetics for surgical procedures. Three common coagulation assays used to
      monitor the effects of new anticoagulant and antithrombotic drugs are thrombin
      time, activated partial thromboplastin time, and prothrombin time. We examined
      the effects of either urethane- or ketamine/xylazine-induced anesthesia on
      variables in the three coagulation assays with blood samples obtained from the
      rats before the induction of anesthesia, compared with samples obtained at 15 or
      60 min after anesthesia induction. Statistically significant differences were
      observed in the ketamine/xylazine group for thrombin time at 60 min (compared
      with control values) and in the urethane group for activated partial
      thromboplastin time at 60 min (compared with control values). In both instances a
      prolongation of times was the effect seen. These results indicate that the choice
      of anesthetic affects the data in certain coagulation assays in the rat and must
      be taken into account when one is planning studies and analyzing results.

PMID- 8872996
TI  - Electrocardiographic changes after intravenous administration of magnesium in
      rabbits.
AB  - Magnesium (Mg+2) therapy has a beneficial effect in various cardiovascular
      diseases. However, overdosage of Mg+2 can be fatal. This study was undertaken to
      determine the amount of Mg+2 that can be safely administered intravenously to
      rabbits. Twenty New Zealand White rabbits were allotted to three groups. One
      hundred milliliters of 0.9% NaCl/kg was infused in group-1 rabbits (n = 10) used
      as a control group. Rabbits in group 2 (n = 6) and group 3 (n = 4) received MgCl2
      (2.5 mmol and 5.0 mmol/kg respectively) in 0.9% NaCl (100 ml/kg). The infusion
      was delivered intravenously for 30 min (group 2, 8 mg/kg per min; group 3, 16
      mg/kg per min). The electrocardiogram was monitored throughout the infusion; the
      P-R interval, QRS duration, and QTc interval of group-2 and group-3 rabbits were
      prolonged at dosages of 0.8 mmol/kg, 1.7 mmol/kg, and 5.0 mmol/kg of MgCl2
      respectively, compared with readings in group-1 rabbits. We hypothesized that the
      mean +2 standard deviations of the pre-operative baseline values was the safe
      limit. On the basis of this hypothesis, the safe limit of the P-R interval is
      95.3 milliseconds, which corresponds to 0.6 mmol/kg of infused Mg+2; the QRS
      duration is 44.4 milliseconds, which corresponds to 1.0 mmol of Mg+2/kg; and the
      QTc interval is 350.0 milliseconds, which corresponds to 3.6 mmol of Mg+2/kg.
      These results will provide guidance for avoiding cardiac side effects when
      researchers investigate the effects of Mg+2 in rabbits.

PMID- 8872997
TI  - Modified procedure with a surgical stapler for construction of a Pavlov pouch in
      dogs.
AB  - An aim of this study was to establish a simple method for the construction of a
      Pavlov pouch that is free of fistula formation between the main part of the
      stomach and the pouch, yet preserves maximal vagal innervation. The Pavlov pouch
      (vagally innervated gastric pouch) was constructed from the greater curvature of
      the gastric corpus at the level of the splenic hilus in four dogs. The plane
      between the mucosal and seromuscular layers was dissected bluntly along the
      medial margin of the pouch. A surgical stapler was introduced into the space
      between the mucosal and seromuscular layers, and the pouch was completely
      separated from the main part of the stomach enterically at the mucosal level but
      remained connected via the seromuscular layers. All dogs survived the operation
      and lost minimal weight; fistulas were not found between the remnant stomach and
      the pouch at necropsy 6 to 8 weeks later. Gastric acid secretion for 30 to 90 min
      after insulin-induced hypoglycemia, which increases vagal tone, was significantly
      increased compared to that before insulin injection, confirming preservation of
      vagal innervation to the pouch. Our technique to create a Pavlov pouch is
      superior to the methods reported previously because of its simplicity, lower
      prevalence of fistula formation, and reliable preservation of vagal innervation
      to the pouch.

PMID- 8872999
TI  - Diagnostic exercise: cutaneous lesions and unilateral hind limb swelling in a
      rhesus monkey.

PMID- 8872998
TI  - Diagnostic exercise: azotemia in a rabbit (Oryctolagus cuniculus).

PMID- 8873000
TI  - Comparative anatomy of the cranial vena cava in laboratory animals.

PMID- 8873001
TI  - Innervation of the liver: morphology and function.
AB  - Although it has been known for many years that the liver receives a nerve supply,
      it is only with the advent of immunohistochemistry that this innervation has been
      analysed in depth. It is now appreciated not only that many different nerve types
      are present, but also that there are significant differences between species,
      especially in the degree of parenchymal innervation. This has stimulated more
      detailed investigation of the innervation of the human liver in both health and
      disease. At the same time, functional studies have been underlining the important
      roles that these nerves play in processes as diverse as osmoreception and liver
      regeneration. This article briefly reviews current understanding of the
      morphology and functions of the hepatic nerve supply.

PMID- 8873002
TI  - Antimitochondrial antibodies in patients with chronic hepatitis C.
AB  - Although autoantibodies have been found in the serum of patients with chronic
      hepatitis C virus (HCV) there has been no convincing evidence of the presence of
      antimitochondrial antibodies, until now. Sera from 460 untreated patients with
      chronic hepatitis C were tested for antimitochondrial antibodies, using an
      indirect immunofluorescence technique; and if they tested positive for the
      antibodies (titer more than 1:50), they also were treated by Western blot
      analysis. Seven (1.5%) sera were positive. None of the patients had biological or
      histological evidence of primary biliary cirrhosis. Antimitochondrial antibodies
      recognized one of the oxo-dehydrogenase multienzyme complexe's epitopes by
      Western blot assay in three patients only. All seven patients were then treated
      by interferon alpha for six months. None showed exacerbation of liver disease
      during treatment. HCV-RNA disappeared from the serum in one patient who became
      negative for anti-M2 antibodies. The four patients who did not respond to
      interferon-alpha therapy, and the two who relapsed after treatment withdrawal,
      had sustained positive antimitochondrial antibodies. These data suggest that: 1)
      antimitochondrial antibodies present in patients with chronic hepatitis C do not
      always recognize the same epitopes as in primary biliary cirrhosis; 2) these
      antibodies may disappear after eradication of HCV, suggesting that the production
      of antimitochondrial antibodies is linked to the presence of the virus and 3) the
      clinical and biological course of chronic hepatitis C, and the response to
      interferon-alpha therapy, does not seem to be different in patients who are
      positive for antimitochondrial antibodies.

PMID- 8873003
TI  - Strain- and sex-specific variations in hepatic glutamine synthetase activity and
      distribution in rats and mice.
AB  - The distribution of glutamine synthetase (GS) in a mammalian liver is restricted
      to a small zone of hepatocytes surrounding the central veins. The determination
      of the size of the GS+ zone in rats by immunohistochemistry revealed that it
      differed between rat strains and was larger in males than in females of each
      strain. Accordingly, the means of the relative mean width (RMW) values that
      characterize the size of the GS+ zone were 19%, 26%, and 39% lower in females
      than in males of Sprague-Dawley, Wistar, and Fischer rats, respectively. Upon
      orchidectomy of male rats, the size of the GS+ zone diminished towards the value
      found in females, while ovariectomy was without effect. This orchidectomy-induced
      reduction was reflected in corresponding changes of the RMW values as well as in
      the number of GS+ cells per pericentral field and was not due to the slightly
      smaller size of the GS+ hepatocytes in the orchidectomized males. No such sex
      difference was found in M775 mice. Biochemical GS activity was higher in the male
      rats than in the female rats and changed correspondingly to the distribution
      after gonadectomy. In the mice, only the specific activity of GS dropped after
      orchidectomy. In primary cultures of rat hepatocytes, no influence of
      testosterone or estrogen on GS activity and cellular distribution was observed,
      even after stimulation of GS activity with dexamethasone and growth hormone. Both
      sex hormones, however, were able to affect the activity of glucose-6-phosphate
      dehydrogenase (G6PD). The observed sex differences in the activity and
      distribution of GS in rat livers suggest that sex hormones not only modulate the
      level of this enzyme but are at least partially involved in the determination of
      the size of the compartment of GS expression. According to the results in the
      cell cultures, the effects of the sex hormones appear indirect rather than
      direct.

PMID- 8873004
TI  - Liver-infiltrating and circulating CD4+ T cells in chronic hepatitis C:
      immunodominant epitopes, HLA-restriction and functional significance.
AB  - The aim was to assess the specificity and functional significance of liver
      infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral
      blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with
      chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a
      proliferative T cell response to at least one of 16 synthetic peptides covering
      highly conserved regions of the core, envelope (El) and non-structural regions
      (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively
      recognized by the proliferating blood mononuclear cells from 46 patients with
      chronic hepatitis C virus infection (79.3%). Fine specificity and HLA-restriction
      were studied with 15 peptide-specific CD4+ T cell lines and 23 T cell clones
      isolated from liver tissue and peripheral blood of 12 patients with chronic
      hepatitis C. It was demonstrated that the peptide-specific response of CD4+ T
      cells was restricted to the presence of autologous accessory cells and HLA-DR and
      -DP molecules. Eight peptide-specific T cell lines and five T cell clones derived
      from liver tissue and peripheral blood, released interferon-gamma (200-6600
      pg/ml) and tumor necrosis factor-alpha (100-400 pg/ml) and no or little
      interleukin-4 (< 140 pg/ml) after peptide-specific or mitogeneic stimulation,
      thus resembling a Th1-like cytokine profile. Patients with active liver disease
      showed significantly higher proliferative responses to hepatitis C virus core
      peptides than asymptomatic hepatitis C virus carriers or complete responders to
      interferon therapy. In conclusion, class II-restricted CD4+ T cell responses to
      some immunodominant epitopes within the hepatitis core region correlated with
      disease activity in chronic hepatitis C virus infection. Functionally, liver
      infiltrating and peripheral blood T cells released Th1-like cytokines in response
      to the specific stimulus. Thus, it can be suggested that CD4+ T cells can mediate
      the pathogenesis of chronic hepatitis C virus induced liver disease.

PMID- 8873005
TI  - Pathogenesis of focal and random hepatocellular necrosis in endotoxemia:
      microscopic observation in vivo.
AB  - The present study was undertaken in rats to clarify the role of sinusoidal
      circulatory disturbances due to fibrin thrombi in the development of focal and
      random hepatocellular necrosis in endotoxemia. Sinusoidal circulation was
      examined microscopically in vivo in rats injected with endotoxin or heparin, or
      both. The sinusoids in places were occluded by adherent fibrin and neutrophils
      soon after endotoxin injection, and subsequently the sinusoidal blood flow
      stagnated, reversed, or detoured. Most of these sinusoidal circulatory
      disturbances recovered in a few hours. However, when the sinusoidal occlusion
      developed simultaneously in clusters of adjacent sinusoids, the sinusoidal
      circulatory disturbance persisted and induced ischemic foci and then
      hepatocellular coagulative necrosis. Pretreatment with heparin definitely
      prevented the adherence of fibrin and neutrophils to the sinusoidal walls, and
      focal hepatocellular necrosis did not appear. These results suggest that focal
      and random hepatocellular necrosis in endotoxemia is caused by circulatory
      disturbances due to fibrin thrombi in clusters of adjacent sinusoids.

PMID- 8873007
TI  - Collagen content in rat liver after experimentally induced cholestasis followed
      by choledochojejunostomy and X-irradiation.
AB  - The right part of the median lobe of the liver of female Wistar rats was
      irradiated, 12.5 or 25 Gy, at a field size of 15 x 20 mm. The central part of the
      irradiated liver lobe was fixed and used for the estimation of the collagen
      protein ratio by means of the Sirius Red-Fast Green extraction method,
      immediately, 8, 16 or 32 weeks after irradiation. No significant increase in
      collagen content could be demonstrated in this time range, both after irradiation
      at 12.5 Gy and at 25 Gy. Partial hepatectomy according to Higgins led to rapid
      regrowth of the remaining liver lobes. The right lobe grew out rapidly to replace
      the median lobe. Two days after partial hepatectomy the right lobe was irradiated
      at the same field size. Measurement of the collagen protein ratio in this
      experiment did not show a significant increase 8, 16 or 32 weeks after
      irradiation. However, the 25 Gy group did not survive long enough to obtain data
      at 16 or 32 weeks. The animals in this latter experiment suffered from ascites
      before dying. Experimentally induced cholestasis was obtained by ligation and
      partial resection of the common bile duct. After two weeks of cholestasis the
      bile flow was restored by Roux-en-Y choledochojejunostomy. The effect of
      irradiation 2 days after repair surgery was studied. Without irradiation the
      collagen protein ratio is increased. Irradiation of the right part of the median
      lobe led to a relatively enhanced collagen content in this lobe. Our results
      indicate that radiation itself does not lead to a significantly enhanced degree
      of fibrosis in the liver. However when an increase in collagen content was
      induced by cholestasis, the partial "dilution" of enhanced fibrosis as a result
      of proliferation of liver parenchyma cells following repair surgery was inhibited
      by irradiation.

PMID- 8873006
TI  - Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat.
AB  - In the present study, we investigated the role of the spleen in experimental
      hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the
      left and middle hepatic lobes, the ischemia was released and the liver was
      reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h
      after the onset of reperfusion, and gradually decreased thereafter. A
      histological examination revealed evidence of hepatocellular necrosis and
      degeneration, especially 24 h after the onset of reperfusion. In addition, there
      was a noticeable accumulation of polymorphonuclear cells in the liver following
      ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion
      reduced both biochemical and histological hepatocellular injury. The number of
      polymorphonuclear cells in the liver following ischemia/reperfusion was
      significantly reduced in rats subjected to splenectomy, suggesting that the
      increase in polymorphonuclear cells may contribute to liver injury. The number of
      mononuclear cells also increased in the marginal zones of the spleen following
      ischemia/reperfusion, and appeared to be derived from the splenic
      monocyte/macrophage population, based on immunohistochemical studies. The spleen
      plays an important role in the pathogenesis of hepatic ischemia/reperfusion
      injury and the splenic monocyte/ macrophage population contributes to liver
      damage.

PMID- 8873008
TI  - Incidence of post-transfusion hepatitis in Taiwan before and after introduction
      of anti-HCV testing.
AB  - The effectiveness of second-generation anti-hepatitis C virus antibody (anti-HCV)
      screening of blood donations for the prevention of non-A, non-B post-transfusion
      hepatitis (NANB PTH) was assessed. A prospective study of 192 transfusion
      recipients was performed to compare the incidence of NANB PTH after the
      introduction of the second-generation anti-HCV test with the incidence before its
      introduction. We used a polymerase chain reaction to detect HCV-RNA and HBV-DNA
      in the sera of patients with NANB PTH. The incidence of acute post-transfusion
      hepatitis C was 11% (8 of 71) before the screening for anti-HCV as compared with
      2.5% (3 of 121) after the screening (p < 0.05). Viremia was detected within the
      first five weeks of infection in 10 patients with acute post-transfusion
      hepatitis C. However, there was no significant difference in the incidence of non
      A, non-B, non-C (NANBNC) PTH before screening (3 of 71, 4.2%) compared with after
      screening (3 of 121, 2.5%). Usually, NANBNC PTH was not clinically important.
      Anti-HCV screening of blood donors significantly reduces the incidence of post
      transfusion hepatitis C, but not the incidence of NANBNC PTH.

PMID- 8873009
TI  - A double-blind, placebo-controlled, pilot trial of thymosin alpha 1 for the
      treatment of chronic hepatitis C.
AB  - A randomized, double-blind, placebo-controlled trial was performed to evaluate
      the efficacy and safety of thymosin alpha 1 (alpha 1) in treating chronic
      hepatitis C. Nineteen Italian patients with chronic active hepatitis C, proven by
      biopsy were randomly assigned to receive a six month course of thymosin alpha 1
      (900 micrograms/m2 of body surface area twice weekly) or a placebo. All had HCV
      RNA in their serum (by PCR), with serum ALT levels more than double the upper
      limit of the normal range for at least six months before enrollment. After
      treatment, patients were followed for an additional six months. All patients
      completed the trial. One patient treated with thymosin alpha 1, but no patient in
      the placebo group, normalized serum ALT levels by the end of the treatment. This
      patient, however, relapsed at the sixth month of the follow up. Overall, there
      were no significant changes in mean serum ALT levels in either group during the
      treatment or follow-up period. No patient cleared HCV-RNA. No side effects were
      reported except for local discomfort at the injection sites, reported by some
      patients treated with thymosin alpha 1. In conclusion, this regimen of thymosin
      alpha 1 is not effective in the treatment of chronic hepatitis C.

PMID- 8873010
TI  - Liver failure in erythropoietic protoporphyria associated with
      choledocholithiasis and severe post-transplantation polyneuropathy.
AB  - In a 58-year-old woman with erythropoietic protoporphyria, asymptomatic liver
      involvement had been diagnosed 12 years earlier. For more than 20 years the
      patient had been known to have symptomatic gallstones. A mild polyneuropathy of
      the lower limbs had been diagnosed several years ago. In December 1992, she
      presented with colicky upper abdominal pain, dyspepsia and mild jaundice.
      Diagnosis of beginning cholestasis in erythrohepatic protoporphyria and
      coincidental choledocholithiasis was made. A causal relation between
      choledocholithiasis and deterioration of liver function was assumed. Endoscopic
      extraction of the bile duct stones, however, could not prevent the development of
      terminal hepatic failure. Biochemically, an excessive protoporphyrinemia and
      coproporphyrinuria were found. Five weeks after presentation, the patient
      underwent orthotopic liver transplantation. Immediately after the operation she
      developed a severe axonal neuropathy with cranial nerve involvement. One year
      after transplantation, her general condition has markedly improved, but there is
      still a disabling polyneuropathy. Recently, there were single reports on patients
      with very similar neurological symptoms following liver transplantation in
      erythropoietic protoporphyria. This case supports the assumption of a distinct
      protoporphyrin-induced neural damage in severe hepatic failure.

PMID- 8873012
TI  - Prostatic carcinoma. Diagnostic pathology and prognosis.
AB  - The pathologic evaluation of prostatic specimens goes well beyond simple
      diagnosis. A number of features can be evaluated which have prognostic
      significance. In addition, evaluation of radical prostatectomy specimens is
      leading to better radiologic correlation, which may lead to improvements in
      imaging protocols.

PMID- 8873011
TI  - Focal tuberculosis of the liver with local hemorrhage in a patient with acquired
      immunodeficiency syndrome.
AB  - Tuberculosis of the liver is common in patients with acquired immunodeficiency
      syndrome (AIDS). Tuberculous liver granulomas in such patients are usually
      atypical. The liver granulomas may be even totally absent, but liver tissue
      usually reveals numerous acid-fast bacilli. Focal tuberculosis of the liver is a
      less common form of liver tuberculous infection. We present a 33-year old white
      homosexual man infected with the human immunodeficiency virus. He had three
      tumour-like lesions in the left liver lobe, which were subsequently diagnosed as
      focal hepatic tuberculosis with local hemorrhage. This unusual presentation of
      liver tuberculosis indicates the necessity of an aggressive diagnostic approach
      for the evaluation of focal liver lesions in patients with AIDS.

PMID- 8873013
TI  - Surgical perspective on prostate cancer. Detection, staging, and treatment.

PMID- 8873014
TI  - The role of MR imaging in the selection of therapy for prostate cancer.
AB  - Combined modality staging is a methodology in which all of the pretreatment
      clinical factors that are found to have independent prognostic significance on
      multivariable analysis for predicting a given outcome (e.g., pathologic stage)
      are used to determine the initial management. This method of staging provides an
      optimized assessment of the pathologic extent of local disease prior to
      management, and therefore is better able to define those patients in whom local
      only therapy is likely to be curative. Knowing more about the pathologic extent
      of disease prior to therapy provides a rationale for patient selection in
      clinical trials that test new management strategies against the current
      standards. The preoperative endorectal coil MR imaging study results have been
      shown on multivariable analysis (which included PSA, clinical stage, and biopsy
      Gleason score) to provide statistically independent prognostic information about
      the outcomes of pathologic stage, margin status, postoperative PSA failure, and
      the prediction of local only failure in the positive margin patient.

PMID- 8873015
TI  - Normal MR anatomy and techniques for imaging of the male pelvis.
AB  - MR imaging has enhanced our ability to evaluate anatomic and pathologic processes
      in the male pelvis. Its remarkable soft-tissue contrast provides a unique
      depiction of the internal anatomy of the pelvic organs. Coupled with this
      superior soft-tissue characterization, its multiplanar capacity allows for
      greater depiction of tumor extension and staging. This article discusses some
      general MR techniques and concepts about MR imaging of the male pelvis and the
      normal MR anatomy and specific MR imaging techniques regarding each of the male
      pelvic organs.

PMID- 8873016
TI  - MR imaging of the prostate and seminal vesicles.
AB  - The important pathologic processes that affect the prostate are reviewed, with an
      emphasis on MR imaging of prostate cancer and benign prostatic hyperplasia. MR
      imaging of the seminal vesicles is also discussed.

PMID- 8873017
TI  - MR staging of prostate cancer. How we can improve our accuracy with decisions
      aids and optimal techniques.
AB  - This article reviews the MR staging of prostate cancer. There has been
      considerable variability in the MR results to date. The reasons are complex and
      include reader experience, the learning curve, and a lack of clear definition of
      the diagnostic features of advanced disease. The problems associated with
      achieving a consistently high degree of accuracy are discussed. The author
      describes a new study aimed at improving radiologists accuracy and illustrates
      some of the findings and specific features of advanced disease that are useful.

PMID- 8873018
TI  - Benefits and costs of MR imaging of prostate cancer.
AB  - This article answers several important questions about the ultimate clinical
      usefulness of prostate MR imaging. How accurate is prostate MR imaging? What are
      the optimal methods for performance and interpretation of the study, considering
      the tradeoffs between false-positive and false-negative results? Is endorectal
      coil imaging a cost-effective part of the prostate examination? And, which men
      are likely to benefit the most from an endorectal prostate examination?

PMID- 8873019
TI  - MR imaging of scrotal, testicular, and penile diseases.
AB  - MR imaging has been successfully applied to a variety of diseases involving the
      scrotum, testes and penis. It offers superior contrast resolution and multiplanar
      imaging capability. This article discusses MR imaging features of normal and
      pathologic conditions.

PMID- 8873020
TI  - MR imaging of bladder diseases.
AB  - The multiplanar and soft-tissue characterization capabilities of MR imaging make
      it a valuable diagnostic tool for imaging the urinary bladder. This article
      reviews the techniques used for MR imaging of the bladder, bladder anatomy, and
      the various MR features of many bladder pathologies.

PMID- 8873021
TI  - Personhood and illness among the Kulina.
AB  - This article offers both a contribution to the ethnography of ethnomedicine among
      the Kulina Indians of western Amazonia--a region in which there has been little
      ethnomedical research--and an extended illustration of the value of the concept
      of "personhood" in the analysis of ethnomedical beliefs and practices. I argue
      that the current medical anthropological fixation on the Body is neither good
      ethnography nor productive theory, and I use the Kulina example to illustrate how
      the cultural dimensions of personhood provide a more satisfactory framework for
      the understanding of illness. Kulina conceptions of illness are closely linked to
      the substances and processes through which personhood is acquired, expressed, and
      transformed. I consider the two major categories of illness in Kulina
      ethnomedicine, and focus special attention on the more serious of these:
      potentially fatal illnesses that are linked to witchcraft and to the violations
      of prohibitions. I suggest how these illnesses serve as languages for the
      simultaneous negotiation of social issues and personhood.

PMID- 8873022
TI  - Of selves and souls, bodies and persons, individuals and societies: a commentary
      on Donald Pollock's "Personhood and illness among the Kulina".

PMID- 8873023
TI  - The body that knows: from Cashinahua epistemology to a medical anthropology of
      lowland South America.
AB  - This article develops an anthropology of the body in its material and social
      environment among the Cashinahua (Huni Kuin) from Brazilian and Peruvian
      Amazonia. The Cashinahua body, it shows, is thought of as produced by others, not
      as growing naturally. Growth can be defined as the corporeal accumulation of
      knowledge in the form of "soul." The article describes the verbal, medical, and
      other techniques used to transform it into "a body that knows." In the Cashinahua
      understanding, a healthy body is one that constantly learns through the senses
      and expresses the accumulated knowledge in social action and speech. An ill body
      is one that no longer knows. Curing, therefore, acts to restore a person's
      capacity to know. The whole article defends the proposition, then, that a prior
      condition for any medical anthropology in the Cashinahua case is a thorough
      examination of Cashinahua epistemology. Finally, through comparative discussion
      of other peoples in lowland South America, it seeks to show that this is also the
      case more widely in the ethnographic region. Ultimately, it suggests that
      ethnography in lowland South America undermines the possibility of a "medical
      anthropology" per se.

PMID- 8873024
TI  - Reflections on Amazonian anthropologies of the body.

PMID- 8873025
TI  - Conceptions of tuberculosis and therapeutic choices in Highland Chiapas, Mexico.
AB  - Tuberculosis continues to be a serious disease among the poor, indigenous
      population of Highland Chiapas, southern Mexico. Ethnographic fieldwork among
      Tzeltal Indians has focused on how cultural perceptions of illness and curing
      influence the Indians' utilization of health care services for tuberculosis
      diagnosis and treatment. This article presents the views on tuberculosis and
      health-seeking activities of several patients in the Tzeltal hamlet of Yochib
      (municipality of Oxchuc). In this community, religious change (Protestantism) and
      the presence of a health clinic promoted biological interpretations of illness
      and acceptance of Western medical treatments. While patients in Yochib do not
      understand tuberculosis in biomedical terms, they nonetheless utilize Western
      services (both local and urban) to obtain treatment. Because of the long duration
      of tuberculosis therapy, however, these patients manifest contrasting attitudes.
      The article focuses on the cultural factors that influence patients' medical
      choices, curing strategies, and their decisions to adhere to long-term treatment
      regimens.

PMID- 8873026
TI  - Alcohol consumption, brothel attendance, and condom use: normative expectations
      among Thai military conscripts.
AB  - This article investigates the relationship between alcohol consumption and
      inconsistent condom use with brothel-based commercial sex workers among Thai
      military conscripts in Northern Thailand. Data from 10 focus groups indicate that
      alcohol consumption (1) is consciously used by men to reduce inhibitions that
      constrain their interpersonal interaction with women and with each other; (2)
      reduces inhibitions of individuals to sexual risk taking; (3) provides a socially
      acceptable excuse for nonuse of condoms; (4) is associated by conscripts with
      brothel attendance; and (5) is seen to enhance male sexual pleasure, in contrast
      to condoms, which are said to reduce pleasure. Understanding the culturally
      defined expectations that surround alcohol consumption and sexual behavior is
      critical for developing realistic interventions to reduce HIV transmission.

PMID- 8873027
TI  - Arrested pregnancy syndrome in Haiti: findings from a national survey.
AB  - This report describes findings from a national survey of pregnant women in Haiti
      regarding the social epidemiology of pedisyon (perdition), or "arrested pregnancy
      syndrome," a condition believed to be associated with infertility. Data collected
      on mortality of respondents' sisters were used to indirectly measure the
      prevalence of this culture-bound syndrome in the adult female population and to
      compare its distribution in urban and rural areas. Perdition appears to be a
      fairly common event that affects a large proportion of Haitian women. Reported
      cases of pedisyon were significantly higher in urban areas, which also differed
      from rural areas on respondent education, economic status, use of prenatal care,
      and fertility. No differences were found on sociodemographic, health, or
      fertility variables when women reporting perdition deaths were compared with
      women who reported other sister deaths. The utility and limitations of the proxy
      respondent method are discussed. Possible explanations for the higher rate of
      pedisyon among urban Haitian women are discussed, and suggestions are made for
      future research on arrested pregnancy syndrome.

PMID- 8873028
TI  - A restoration algorithm for P-32 and Y-90 bremsstrahlung emission nuclear
      imaging: a wavelet-neural network approach.
AB  - A novel wavelet-based neural network (WNN) filter is proposed for image
      restoration as required for imaging of beta emitters by bremsstrahlung detection
      using a gamma camera. Quantitative imaging of beta emitters is important for the
      in vivo management of antibody therapy using either P-32 or Y-90. The theoretical
      basis for the general case for M-channel multiresolution wavelet decomposition of
      the nuclear image into different subimages is developed with the objective of
      isolating the signal from noise. A modified Hopfield neural network (NN)
      architecture is then used for multichannel image restoration using the dominant
      signal subimages. The NN model avoids the common inverse problem associated with
      other image restoration filters such as the Wiener filter. The relative
      performance of the WNN for image restoration, for M = 2 channel, is compared to a
      previously reported order statistic neural network hybrid (OSNNH) filter.
      Initially simulated degraded images of known structures with different noise
      levels are used. Quantitative metrics such as the normalized mean square error
      (NMSE) and signal-to-noise ratio (SNR) are used to compare filter performance.
      The WNN yields comparable results for image restoration with suggested slightly
      better performance for the images with higher noise levels as often encountered
      in bremsstrahlung detection. Attenuation measurements were performed using two
      radionuclides, 32P and 90Y as required for calibration of the gamma camera for
      quantitative measurements. Similar values for an effective attenuation
      coefficient were observed for the restored images using the OSNNH filters (32P:
      mu = 0.122 cm-1, 90Y: mu = 0.135 cm-1) and WNN (32P: mu = 0.122 cm-1, 90Y: mu =
      0.135 cm-1) filters with slightly higher values obtained for the raw data (32P:
      mu = 0.142 cm-1, 90Y: mu = 0.142 cm-1) for a 3.5-cm source size. The WNN,
      however, was computationally more efficient by a factor of 4 to 6 compared to the
      OSNNH filter. The filter architecture, in turn, is also optimum for parallel
      processing or VLSI implementation as required for planar and particularly for
      SPECT mode of detection.

PMID- 8873029
TI  - Image compression in digital mammography: effects on computerized detection of
      subtle microcalcifications.
AB  - Our previous receiver operating characteristic (ROC) study indicated that the
      detection accuracy of microcalcifications by radiologists is significantly
      reduced if mammograms are digitized at 0.1 mm x 0.1 mm. Our recent study also
      showed that detection accuracy by computer decreases as the pixel size increases
      from 0.035 mm x 0.035 mm. It is evident that very large matrix sizes have to be
      used for digitizing mammograms in order to preserve the information in the image.
      Efficient compression techniques will be needed to facilitate communication and
      archiving of digital mammograms. In this study, we evaluated two compression
      techniques: full frame discrete cosine transform (DCT) with entropy coding and
      Laplacian pyramid hierarchical coding (LPHC). The dependence of their efficiency
      on the compression parameters was investigated. The techniques were compared in
      terms of the trade-off between the bit rate and the detection accuracy of subtle
      microcalcifications by an automated detection algorithm. The mean-square errors
      in the reconstructed images were determined and the visual quality of the error
      images was examined. It was found that with the LPHC method, the highest
      compression ratio achieved without a significant degradation in the detectability
      was 3.6:1. The full frame DCT method with entropy coding provided a higher
      compression efficiency of 9.6:1 at comparable detection accuracy. The mean-square
      errors did not correlate with the detection accuracy of the microcalcifications.
      This study demonstrated the importance of determining the quality of the
      decompressed images by the specific requirements of the task for which the
      decompressed images are to be used. Further investigation is needed for selection
      of optimal compression technique for digital mammograms.

PMID- 8873030
TI  - Quantitative classification of breast tumors in digitized mammograms.
AB  - The goal of this study was to develop a technique to distinguish benign and
      malignant breast lesions in secondarily digitized mammograms. A set of 51
      mammograms (two views/patient) containing lesions of known pathology were
      evaluated using six different morphological descriptors: circularity, mu R/sigma
      R (where mu R = mean radial distance of tumor boundary, sigma R = standard
      deviation); compactness, P2/A (where P = perimeter length of tumor boundary and A
      = area of the tumor); normalized moment classifier; fractal dimension; and a
      tumor boundary roughness (TBR) measurement (the number of angles in the tumor
      boundary with more than one boundary point divided by the total number of angles
      in the boundary). The lesion was segmented from the surrounding background using
      an adaptive region growing technique. Ninety-seven percent of the lesions were
      segmented using this approach. An ROC analysis was performed for each parameter
      and the results of this analysis were compared to each other and to those
      obtained from a subjective review by two board-certified radiologists who
      specialize in mammography. The results of the analysis indicate that all six
      parameters are diagnostic for malignancy with areas under their ROC curves
      ranging from 0.759 to 0.928. We observed a trend towards increased specificity at
      low false-negative rates (0.01 and 0.001) with the TBR measurement. Additionally,
      the diagnostic accuracy of a classification model based on this parameter was
      similar to that of the subjective reviewers.

PMID- 8873031
TI  - The effect of x-ray beam alignment on the performance of antiscatter grids.
AB  - While the qualitative effects of grid misalignment are known, we have quantified
      the effect of different degrees of grid misalignment on image contrast and
      patient exposure. Radiographs were made of a phantom consisting of five lead
      disks on top of a 15 cm block of lucite. Four 60 lines/cm grids, having grid
      ratios of 3:1, 4:1, 6:1, and 8:1 were used. When the tube was angled more than
      three degrees across the grid lines, the contrast improvement factor decreased
      substantially for all four grids, as much as 46% for an 8:1 grid with a 12
      degrees misalignment. There was a concomitant decrease in film optical density,
      which if compensated for by an increase in patient exposure, would lead to a
      higher effective bucky factor. With the exception of the 3:1 grid, if the grid is
      misaligned by more than 6 degrees, higher signal-to-noise ratios can be attained
      by removing the grid and using the increased patient exposure to reduce noise.

PMID- 8873032
TI  - Basic imaging properties of a new screen-film system for chest radiography.
AB  - To evaluate the potential clinical usefulness of a new screen-film system
      (advanced screen-film system; AD system) for chest radiography, its fundamental
      imaging properties compared with a conventional screen-film system (HR-4/HR-S)
      were investigated. The basic imaging properties were evaluated by measuring
      characteristic (H&D) curves, relative speeds, MTFs (modulation transfer
      functions), WS (Wiener spectra), and x-ray attenuations of screens. The detail
      visibilities and pathological details of various diseases in chest radiographs of
      patients were evaluated subjectively. The film gradient of the AD system was
      slightly lower at low radiographic density, and higher at high density, as
      compared with a conventional screen-film system. The screen speed of the AD
      system was 212% greater than that of the conventional system, and the film speed
      was 53% that of the conventional film. As the result, the total speed of the AD
      system was slightly higher compared with the conventional system. The spatial
      resolution of the AD system was comparable to or slightly lower than that of the
      conventional system. The noise level of the AD system was considerably lower than
      that of the conventional system at low (D = 0.5) and middle (D = 1.0)
      radiographic density levels. However, it was high at high radiographic density (D
      = 1.8). The radiographic densities in the underpenetrated areas with the AD
      system were greater than those of the conventional system when the lung densities
      are matched comparable. Improvement in noise level with the AD system at low and
      middle density levels may be useful for detection of various diseases in chest
      radiographs.

PMID- 8873033
TI  - A Fourier based algorithm for tracking SPAMM tags in gated magnetic resonance
      cardiac images.
AB  - A method is described for automatically tracking spatial modulation of
      magnetization tag lines on gated cardiac images. The method differs from
      previously reported methods in that it uses Fourier based spatial frequency and
      phase information to separately track horizontal and vertical tag lines. Use of
      global information from the frequency spectrum of an entire set of tag lines was
      hypothesized to result in a robust algorithm with decreased sensitivity to noise.
      The method was validated in several ways: first, actual tagged cardiac images at
      end diastole were deformed known amounts, and the algorithm's predictions
      compared to the known deformations. Second, tagged, gated images of the thigh
      muscle (assumed to have similar signal to noise characteristics as cardiac
      images, but to not deform with time) were created. Again the algorithmic
      predictions could be compared to the known (zero magnitude) deformations and to
      thigh images which had been artificially deformed. Finally, actual cardiac tagged
      images were acquired, and comparisons made between manual, visual, determinations
      of tag line locations, and those predicted by the algorithm. At 0.5 T, the mean
      bias of the method was < 0.34 mm even at large deformations and at late (noisy)
      times. The standard deviation of the method, estimated from the tagged thigh
      images, was < 0.7 mm even at late times. The method may be expected to have even
      lower error at higher field strengths.

PMID- 8873034
TI  - An automatic contour extraction algorithm for short-axis cardiac magnetic
      resonance images.
AB  - In this article an automatic process is presented for the extraction of the left
      ventricular contours. The only operator-supplied information is the location of a
      single point within the left ventricle. The raw data for processing are short
      axis cardiac MR images, obtained using various MRI protocols. In this study we
      considered only protocols for which the blood appears dark. The proposed
      algorithm performs smoothing and thresholding of the original MR images, and uses
      the segmented images to form edge images. From those edge images the endocardial
      curve is extracted using a modified contour following approach. The algorithm can
      accommodate moderate noise and small gaps in the contour. A smooth curve that
      approximates the epicardium is then obtained using a method combining radial
      search and FFT based smoothing. The quality of the obtained contours was visually
      assessed by three observers. Their evaluation shows that the algorithm is
      successful when images of reasonable quality are processed. Further evaluation
      work is required in order to fully assess the performance and limitation of the
      suggested method.

PMID- 8873035
TI  - Modeling dose distributions from portal dose images using the
      convolution/superposition method.
AB  - Post-treatment dose verification refers to the process of reconstructing
      delivered dose distributions internal to a patient from information obtained
      during the treatment. The exit dose is commonly used to describe the dose beyond
      the exit surface of the patient from a megavoltage photon beam. Portal imaging
      provides a method of determining the dose in a plane distal to a patient from a
      megavoltage therapeutic beam. This exit dose enables reconstruction of the dose
      distribution from external beam radiation throughout the patient utilizing the
      convolution/superposition method and an extended phantom. An iterative
      convolution/superposition algorithm has been created to reconstruct dose
      distributions in patients from exit dose measurements during a radiotherapy
      treatment. The method is based on an extended phantom that includes the patient
      CT representation and an electronic portal imaging device (EPID). The
      convolution/superposition method computes the dose throughout the extended
      phantom, which allows the portal dose image to be predicted in the EPID. The
      process is then reversed to take the portal dose measurement and infer what the
      dose distribution must have been to produce the measured portal dose. The dose
      distribution is modeled without knowledge of the incident intensity distribution,
      and includes the effects of scatter in the computation. The iterative method
      begins by assuming that the primary energy fluence (PEF) at the portal image
      plane is equal to the portal dose image, the PEF is then back-projected through
      the extended phantom and convolved with the dose deposition kernel to determine a
      new prediction of the portal dose image. The image of the ratio of the computed
      PEF to the computed portal dose is then multiplied by the measured portal dose
      image to produce a better representation of the PEF. Successive iterations of
      this process then converge to the exiting PEF image that would produce the
      measured portal dose image. Once convergence is established, the dose
      distribution is determined by back-projecting the PEF and convolving with the
      dose deposition kernel. The method is accurate, provided the patient
      representation during treatment is known. The method was used on three phantoms
      with a photon energy of 6 MV to verify convergence and accuracy of the algorithm.
      The reconstructed dose volumes agree to within 3% of the forward computation dose
      volumes. Furthermore, this technique assumes no prior knowledge of the incident
      fluence and therefore may better represent the dose actually delivered.

PMID- 8873036
TI  - Verification and correction of setup deviations in tangential breast irradiation
      using EPID: gain versus workload.
AB  - PURPOSE: When a deviation in the treatment setup is identified, when or how
      should it be corrected? With the aim of improving the precision and reducing the
      systematic errors while maintaining the workload to a minimum, a study was
      performed to define the proper set of actions for the correction of tangential
      breast setup deviations during the course of the treatment. PATIENTS AND METHODS:
      Clinical data were taken from a prospective study of more than 2200 on-line
      Electronic Portal Images (EPI) from 20 patients treated with tangential
      irradiation following a partial mastectomy for an early stage (I and II) breast
      cancer. The values of the central lung distance were then entered in the
      verification/correction procedure and modified to correct only the portion of the
      deviation most likely attributed to systematic errors according to the maximum
      likelihood. The verification/ correction procedure uses an action level equal to
      FML x alpha/square root of N, where alpha is proportional to the standard
      deviation (alpha = n sigma) and N is the number of consecutive fractions
      delivered after the start of the treatment. FML is the fraction of the deviation
      due to the systematic errors estimated from the maximum likelihood of the two
      distributions. In addition to n, one needs to specify Nmax, the maximum number of
      consecutive measurements without correction, to apply the procedure. The
      combination of these two parameters C(n,Nmax) will determine the reduction of
      systematic errors (gain) and the number of measurements and corrections
      (workload) associated to the procedure. RESULTS: The effects of three
      combinations, C(1,1), C(2,2), and C(3,4) were studied. Also, the analysis of the
      results after application of the procedure with and without the factor of maximum
      likelihood made individually for each patient demonstrates the importance of the
      FML. CONCLUSIONS: The verification/correction procedure with the inclusion of the
      FML can effectively improve the accuracy when applied to clinical data. With the
      specific workload related to measurements and corrections performed at our
      institution, we have found that in the case of the tangential breast treatment,
      the optimum combination uses an action level equal to 2 sigma and a maximum of
      two consecutive measurements without correction.

PMID- 8873037
TI  - Effects of irradiation geometry on treatment plan optimization with linac-based
      radiosurgery.
AB  - A comparison was made of different treatment plans to determine the effect on the
      three-dimensional dose distributions of varying the allowed parameters in linac
      based stereotactic radiosurgery with circular collimators; these parameters are
      arc position, length, and weighting, and collimator diameter. For the class of
      eccentrically shaped target volumes that are not so irregular as to require
      several separate isocenters, it was found that superior dose distributions could
      be achieved by varying arc length, arc position, arc weighting, and collimator
      diameter. An analysis of the results achieved with an automated planning program
      indicates that, in general, the variables of arc position and arc length are of
      greater importance than collimator size or beam weighting. However, there are
      cases where varying these latter two parameters does result in markedly better
      dose distributions. A deeper investigation into the effects of multiple
      collimators on the dose distribution in the area of steepest gradient
      demonstrated that multiple collimator sizes do not significantly degrade the dose
      falloff, which is in fact mostly determined by the effects of intersecting arcs.

PMID- 8873038
TI  - The effect of detector size to the broadening of the penumbra--a computer
      simulated study.
AB  - The effect of detector size to the broadening of the measured beam penumbra has
      been a subject of numerous studies. Based on measured data, linear and quadratic
      curves have been proposed to describe the relationship between the measured
      penumbra width, between 10%-90% and 20%-80% intensities, and the detector size.
      Extrapolations of these curves to zero detector size also suggest that the
      inherent penumbras can be deduced. However, due to experimental noise, especially
      when a small ionization chamber is used, and the inherent penumbra is not known,
      it is difficult to discern the superiority of either model. In this study, one
      dimensional convolution using a thin circular disk shape detector was employed to
      analyze the effect of detector size to the broadening of the penumbra. A set of
      beams with different inherent penumbra widths, ranging from 0 to 350 in arbitrary
      unit, was first generated. Each beam was then convoluted with the response
      function of the detectors with different sizes from 10 to 280, in arbitrary unit.
      The result is an output signal with penumbra that is wider than the inherent
      penumbra. The plots of penumbra widths to detector radii are a family of concave
      parabolic curves with different inherent penumbra widths. The concave portions of
      the curve represent results from scanning with detectors equal to or smaller than
      the penumbra width, and the linear portions represent results from scanning with
      detectors much larger than the penumbra. The curves are nothing but different
      scales of one curve. The extrapolations of the curves to the penumbra axis when
      the detector radius approaches zero give the deduced inherent penumbra widths.
      The deduced inherent penumbra widths approximate the inherent penumbra widths
      satisfactorily. From the graphs provided, the inherent penumbra can be deduced
      using the detector radius and the measured penumbra width.

PMID- 8873039
TI  - Surface dose measurements for highly oblique electron beams.
AB  - Clinical applications of electrons may involve oblique incidence of beams, and
      although dose variations for angles up to 60 degrees from normal incidence are
      well documented, no results are available for highly oblique beams. Surface dose
      measurements in highly oblique beams were made using parallel-plate ion chambers
      and both standard LiF:Mg, Ti and carbon-loaded LiF Thermoluminescent Dosimeters
      (TLD). Obliquity factors (OBF) or surface dose at an oblique angle divided by the
      surface dose at perpendicular incidence, were obtained for electron energies
      between 4 and 20 MeV. Measurements were performed on a flat solid water phantom
      without a collimator at 100 cm SSD. Comparisons were also made to collimated
      beams. The OBFs of surface doses plotted against the angle of incidence increased
      to a maximum dose followed by a rapid dropoff in dose. The increase in OBF was
      more rapid for higher energies. The maximum OBF occurred at larger angles for
      higher-energy beams and ranged from 73 degrees for 4 MeV to 84 degrees for 20
      MeV. At the dose maximum, OBFs were between 130% and 160% of direct beam doses,
      yielding surface doses of up to 150% of Dmax for the 20 MeV beam. At 2 mm depth
      the dose ratio was found to increase initially with angle and then decrease as
      Dmax moved closer to the surface. A higher maximum dose was measured at 2 mm
      depth than at the surface. A comparison of ion chamber types showed that a
      chamber with a small electrode spacing and large guard ring is required for
      oblique dose measurement. A semiempirical equation was used to model the dose
      increase at the surface with different energy electron beams.

PMID- 8873040
TI  - Laser heating of thermoluminescent plates: application to intraoperative
      radiotherapy.
AB  - A new system of radiation dose mapping based on laser heating of
      thermoluminescent dosimetric plates (TLDP) has been developed. Application of
      this technique to intraoperative radiotherapy (IORT) has been investigated.
      Preliminary results show that TLDP are a possible alternative to radiological
      films and ionization chambers since they provide some advantages such as 2D dose
      measurements with digital storage, large dynamic dose range, and easy processing.

PMID- 8873041
TI  - Customization of a radiation management system to support in vivo patient
      dosimetry using diodes.
AB  - Considerable effort is generally made in the quality control of radiation therapy
      units and in patient chart checking to ensure accurate delivery of treatment to
      the patients. Record and verify (RV) systems have been implemented which will
      inhibit the beam from being turned ON if the parameters set on the medical linear
      accelerators do not match a preprogrammed file. It should be emphasized, however,
      that RV systems are designed only to ensure proper setup of parameters on the
      therapy units and bear no direct link with proper patient position. The only real
      link between treatment planning and delivery to the patient is in-vivo dosimetry.
      Diodes provide a convenient way of measuring the dose received by the patient in
      real time and, after the initial tedious calibrations, require very little
      additional effort. In order to facilitate diode use by the therapists in our
      institution, the radiation management system (RMS) database in use with our
      linear accelerators was interfaced with the output obtained from a commercially
      available diode dosimetry system. The chart printout format was altered to read
      this value from the RMS database allowing a near real-time recording of the
      actual dose received by the patient for up to three sites concurrently. This
      provides for an immediate additional check to the planned and received doses
      already recorded by the RMS RV software. This procedure, if carried out during
      the first treatment and subsequently on a weekly basis, would ensure that
      differences of the order of 5% or larger between planned and delivered dose would
      not go undetected.

PMID- 8873042
TI  - Implications of 3-dimensional target shape and motion in aperture design.
AB  - To determine the shape of a radiation beam aperture a margin is typically applied
      to the clinical target volume (CTV) to yield the planning target volume (PTV),
      and the aperture is then determined from the projection of the PTV onto the
      aperture plane. This margin accounts for setup variability and organ motion
      originating from respiration or other physiologic processes. The use of either a
      uniform margin, or alternatively one which takes into account only the expected
      magnitude and direction of target motion, fails to account for the three
      dimensional nature of the target; such a method neglects the volumetric effect of
      target shape on the fractional target volume irradiated when the target shifts
      partially out of the aperture. A mathematical framework is developed to analyze
      and illustrate the consequences of irradiating an irregular target shape in the
      presence of target motion. The effect of target shape on volume coverage is
      demonstrated for selected cases involving conventional BEV aperture design
      techniques. The volumetric implications of target shape are considered from two
      complementary points of view. The first involves transformation into a
      "displacement space," which isolates the volumetric effect of the shape of the
      target allowing it to be studied independently of the probability distribution of
      target motion. The second point of view combines the effects of the 3D target
      shape and the probability distribution of motion in a manner independent of beam
      direction to yield a 3D "target distribution." The two points of view represent
      distinct starting points for computation of the expected value of fractional
      target volume coverage in the presence of target motion. In certain cases it may
      be beneficial to (1) employ "target distributions" for the target and normal
      tissues in place of the conventional static PTV and, (2) include the aperture
      shape, on equal footing with parameters such as beam weights and energies, into a
      quantitative optimization process explicitly accounting for uncertainties in the
      position of the target volume and critical structures.

PMID- 8873043
TI  - Europium-152 as a potential substitute for cobalt-60 in radiation therapy.
AB  - Construction has begun of prototype europium-152 sources, with the principal goal
      of providing cost-effective teletherapy for emergent nations where prices for
      cobalt-60 are excessive, owing to replacement needs, and the use of linacs is
      economically prohibitive and technologically unfeasible. 152Eu sources (T1/2 =
      13.4y vs T1/2 = 5.26y for 60Co) are designed for absorbed dose rates > 1.5 Gy/min
      at 1 m, with specific activities > 5 TBq/gm, allowing substitution into existing
      irradiators. Costs of 152Eu compare favorably with 60Co, taking account of
      extended useful lifetime.

PMID- 8873044
TI  - Photon absorbed fractions for cylindrical geometry: homogeneous nonradioactive
      cylinder containing a homogeneous cylindrical distribution of activity.
AB  - The purpose of this study was to calculate photon absorbed fractions in tissue
      surrounding a radioactive source where both the source and the surrounding tissue
      are assumed to have cylindrical geometry. Specifically, we treated two cases: the
      case of a cylindrical source of homogeneous activity placed in air, and second,
      the case of a cylindrical source of homogeneous activity placed in a cylindrical
      nonradioactive absorbing material. In this study we offer an analytical solution
      to these problems followed by numerical integration. The computer program allowed
      for very general calculations, e.g., different tissues, different geometrical
      setups. Tables of absorbed fractions have been developed for commonly used
      radionuclide energies and tissue-equivalent material. A comparison between our
      results and the results of other related studies showed the advantages and
      limitations of this approach.

PMID- 8873045
TI  - EGS4 dosimetry calculations for cylindrically symmetric brachytherapy sources.
AB  - Computer algorithms for electron binding correction to Compton scattering and for
      detailed simulation of K-edge characteristic x-ray production were incorporated
      into EGS4 unix version 2.0. Based on detailed modelling of the internal
      structures of sources, the modified version was used to calculate dose rate
      constants, radial dose functions, and anisotropy functions on the long axis for
      an 125I model 6711 source, 169Yb Type 5 and Type 8 sources, and a stainless steel
      clad (SS) 192Ir source. The geometry of these sources is cylindrically symmetric.
      Calculated results are generally in good agreement with corresponding values
      recommended by TG-43 and Monte Carlo results published by other authors. The
      influence of electron binding in Compton scattering on the calculated dose
      distribution for an 125I model 6711 source in water, and of different
      characteristic x-ray production models for 125I model 6711 and 192Ir SS sources,
      were also studied.

PMID- 8873046
TI  - The control of gene expression in melanocytes and melanomas.
AB  - Powerful evidence exists that deregulation of cell type-specific gene expression
      is a major feature of the genesis of several cancers, with many oncogenic
      proteins known to possess transcription regulation properties. As a consequence
      of this deregulation, melanomas may ectopically express HLA-DR and also fall to
      express enzymes required for melanin synthesis, resulting in amelanotic melanoma.
      Recent work has demonstrated that these phenomena may be accounted for by the
      expression of a transcription factor called Brn-2, now known to be involved with
      the development of neural crest-derived tissues. Brn-2 is normally expressed at
      high levels in melanoblasts and melanomas but only at low levels in normal
      melanocytes. Brn-2 may act by competing with another transcription factor, ml,
      necessary for normal melanocyte development.

PMID- 8873047
TI  - Expression of the tumour suppressor genes p15 and p16 in malignant melanoma.
AB  - Recent evidence has suggested the presence of a malignant melanoma (MM)-related
      gene on human chromosome 9p21, the location of the putative tumour suppressor
      genes p15 and p16. DNA from patients with familial MM, from MM cell lines and
      sporadic MM cases has been examined for coding region and splice junction
      mutations of the p16 gene, but expression studies of both genes from the same
      cells have not been reported. We used the polymerase chain reaction to analyse
      p16 and p15 expression in 23 MM cell lines. Fourteen lines (61%) did not express
      either gene. Six (26%) expressed p16 and eight (35%) expressed p15. Expression
      patterns were concordant in most cases (83%), but one line (4%) expressed only
      p16 and three lines (13%) expressed only p15. These data suggest that loss of
      function of these genes, as judged by expression, may be higher than predicted by
      previous DNA-based studies. The lack of complete concordance between p15 and p16
      expression implies that the genes are not functionally redundant and that loss of
      either gene may be important in the pathogenesis of MM.

PMID- 8873048
TI  - Anti-melanoma monoclonal antibody HMB-45 on enhanced chemiluminescence-western
      blotting recognizes a 30-35 kDa melanosome-associated sialated glycoprotein.
AB  - HMB-45 is an anti-melanoma monoclonal antibody widely used in diagnostic
      pathology owing to its great specificity in identifying poorly differentiated
      melanomas. In this study, by a series of sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis (SDS-PAGE) immunoblots with the enhanced chemiluminescent
      (ECL) detection method on the HU-214 melanoma cell line, we identified the
      antigen of HMB-45 in a protein or proteins of 30-35 kDa. Although this result is
      in discrepancy with the previous literature which identified the antigen as a
      protein of 7 or 10 kDa, a family of proteins of 25-70 kDa of as a protein of 100
      kDa (gp100), the present data indicate that the antigen signal we found might be
      specific. Furthermore, immunoblots on neuraminidase-treated cell lysates show, in
      agreement with already published data, that the antigen might be a sialated
      glycoprotein with the sialic acid involved in the epitope. Immunoblots on
      partially purified melanosomes confirmed the presence of the antigen in these
      organelles.

PMID- 8873049
TI  - Allogeneic murine melanoma cell vaccine: a model for the development of human
      allogeneic cancer vaccine.
AB  - In an attempt to induce an immune response against tumour antigens, several
      groups are transfecting cytokine and other genes into autologous tumour cells
      which are given to the patient as a vaccine. This process is labour-intensive,
      time-consuming and expensive. Allogeneic cells would offer a more convenient
      vehicle for the delivery of cytokines and other molecules. However, current dogma
      suggests that MHC-matched cells are a prerequisite for an effective immune
      response. Using murine melanoma models we compared allogeneic and autologous
      vaccination and showed that the survival of C56BL/6 mice (H-2b) was prolonged
      with some degree of protection achieved against an autologous B15-F10 (H-2b) cell
      challenge when the mice were vaccinated with allogeneic K1735-M2 (H-2k) cells but
      not when immunized with autologous B16-F10 cells. Both vaccination with live and
      irradiated allogeneic cells induced an anti-tumour effect using only one
      immunization and no boost or adjuvant. Protection was not observed after
      vaccination with another melanoma (S91; H-2d) or with a carcinoma (A9HT; H-2k).
      Allogeneic vaccination promoted a cytotoxic cellular response against both the
      allogeneic and the syngeneic melanomas. This allogeneic vaccination model will be
      useful for studying the underlying mechanisms of protection, in both pre- and
      post-challenge settings, as well as for developing whole cell vaccination systems
      using genetically modified allogeneic tumour cells.

PMID- 8873050
TI  - Regulation of interleukin-8 mRNA expression and protein secretion in a melanoma
      cell line by tumour necrosis factor-alpha and interferon-gamma.
AB  - Interleukin-8 (IL-8) is a cytokine that is thought to promote melanoma tumour
      progression. We evaluated and adapted a non-radioactive, reverse transcriptase
      polymerase chain reaction method for semiquantitative analysis of IL-8 mRNA
      expression. Using this technique we studied the regulation of IL-8 levels in the
      melanoma cell line Colo 38. Seeding of melanoma cells into culture dishes
      resulted in a significant increase of IL-8 expression, which could be attributed
      to adherence. A pronounced increase of IL-8 mRNA expression and protein
      production was induced by tumour necrosis factor-alpha (TNF alpha). Interferon
      gamma (IFN gamma) partially inhibited TNF alpha-induced IL-8 secretion, whereas
      no influence on IL-8 mRNA levels was detected. The inhibitory affect of IFN gamma
      on melanoma cells is in contrast to its stimulatory effect on melanocytes.

PMID- 8873051
TI  - Accuracy of case-reported family history of melanoma in Queensland, Australia.
AB  - A positive family history is used in clinical practice as an indication of
      increased melanoma risk, yet there are no data on the accuracy of reported family
      histories of melanoma. The validity of case-reported family history of melanoma
      was assessed in the course of a family and twin study of melanoma in Queensland,
      Australia, conducted among the families of 2,118 melanoma cases diagnosed in
      Queensland between 1982 and 1990. A total of 913 melanoma cases made 1,267
      reports of melanoma among their first-degree relatives. A total of 1,040 of these
      reports were checked, first through relatives themselves and then, if the
      relative also said they had had melanoma, through the relative's medical records.
      Medical confirmation of melanoma as the diagnosis was obtained for 623 reports
      (59.9%; 95% confidence interval 56.9-62.9): a false-positive reporting rate by
      cases of 40.1%. The level of false-positive reporting was lower for cases under
      70 years of age, for women, for cases whose own diagnosis of melanoma was more
      than 5 years earlier, and for cases with three or more relatives with melanoma.
      Media campaigns in Queensland aimed at increasing skin cancer awareness, and
      confusion between melanoma and other more common actinic neoplasma (basal and
      squamous cell carcinomas), may partly explain the high false-positive reporting
      rate observed here. For this reason, It is difficult to generalize these findings
      to northern hemisphere populations where skin cancer is not such an important
      public health issue.

PMID- 8873052
TI  - Exploration of interactions between prognostic factors of stage I malignant
      melanoma.
AB  - While many studies have sought prognostic factors of malignant melanoma using
      multivariate survival models, the interaction between predictors has been much
      less studied. We have studied data from 1,560 patients with stage I melanoma
      collected at the Cancer Registry of the Canton of Zurich over the period 1980
      1990 and explored interactions between predictors by identifying two separate
      multivariate Cox models for men and women and investigating two-way interactions
      between predictors in each model. Considerable differences between models for man
      and women were observed. In particular, in women a pronounced interaction between
      'histology' and 'Clark level' was identified. Without this interaction
      'histology' and 'Clark level' are not significant but when the interaction term
      was included both predictors become significant. Thus, omission of an interaction
      term may preclude the recognition of main effects ('masking'). For female
      patients with nodular tumours prognosis is essentially independent of Clark
      level. In contrast, for female patients with non-nodular tumours, prognosis was
      found to be strongly dependent on Clark level. In the case of Clark level 2
      prognosis was extremely good: no patient was observed to die from melanoma. We
      conclude that it may be worth considering interaction terms. With large enough
      sample sizes it may be preferable to stratify patients into subgroups and to
      identify separate models for each stratum instead of having to cope with
      interactions of higher order.

PMID- 8873053
TI  - Positron emission tomography in the detection and management of metastatic
      melanoma.
AB  - Initial reports suggest that positron emission tomography with
      [18F]fluorodeoxyglucose (FDG-PET) may offer greater diagnostic accuracy and
      versatility than conventional radiology in staging patients with metastatic
      melanoma. We reviewed the first 100 melanoma patients to have PET imaging at our
      institution. PET findings were correlated with all other available results,
      including plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging,
      bone scintigraphy, clinical findings and histopathology. A total of 415
      metastatic lesions were evaluated, 388 (93%) of which were detected by PET. In 20
      patients, PET detected 24 metastases up to 6 months earlier than conventional
      imaging or physical examination. Selection of surgical or medical management was
      specifically influenced by PET findings in 22 patients, and PET was used to
      clarify another 12 cases where CT was inconclusive. In nine patients undergoing
      chemotherapy, PET was used to assess response to treatment. We conclude that FDG
      PET can accurately detect metastatic melanoma with a single non-invasive scan,
      and can demonstrate some metastases months before conventional imaging
      techniques. PET can improve the selection of patients for surgery, has potential
      for monitoring response to treatment and may prove a cost-effective means of
      staging melanoma patients.

PMID- 8873054
TI  - Complete responses and survival after polychemotherapy plus interferon-alpha for
      patients with metastatic melanoma.
AB  - One hundred and one patients with metastatic melanoma were treated with three
      different dacarbazine (DTIC)-based polychemotherapy plus recombinant interferon
      (IFN) alpha-2b regimens in multicentre phase II trials in Finland during 1986
      1993. The regimens were DTIC, nimustine (ACNU) plus IFN and two different
      schedules of DTIC, vincristine, bleomycin, lomustine (CCNU) plus IFN. There were
      14 patients with complete response (CR) and 12 patients with partial response,
      with estimated median survivals of 44 months and 13 months respectively. The
      median survival was 14 months for 22 patients with stable disease, and 6 months
      for the 53 patients who had progressive or non-evaluable disease. The median
      progression-free interval was 6 months and the median survival 9 months for the
      whole group. Thirty-nine percent of patients survived at least 1 year and 17% at
      least 2 years. Age, sex, primary tumour site, Clark's level, disease-free
      interval, prior therapy of recurrence and metastatic sites of patients who
      achieved CR were compared with those of other patients. In addition, the
      predictive value of these factors for survival was analysed. Prior therapy of
      recurrent disease (none, surgery or surgery plus radiotherapy) and metastatic
      profile (soft tissue or lung, one or two sites) were associated with CR in
      univariate analysis, while in multivariate analysis only prior therapy was found
      to be an independent prognostic factor. Prior surgery plus radiotherapy, soft
      tissue or lung metastases and response to present chemo-immunotherapy were
      significant predictors of favourable survival in univariate analysis. In
      multivariate analysis only response was an independent prognostic factor.

PMID- 8873055
TI  - Autonomic nervous system as a model of neuronal aging: the role of target tissues
      and neurotrophic factors.
AB  - The aim of this study was to determine the role of target tissues and
      neurotrophic factors in the growth and atrophy of autonomic neurons during
      development and aging. Using quantitative neuroanatomical techniques, it is shown
      that, although axonal and dendritic growth is apparent throughout postnatal
      development, different patterns of growth are found in autonomic neurons
      innervating different target tissues. For example, sympathetic neurons
      innervating the submandibular gland continue to grow well into maturity, but
      those innervating the iris cease net growth early in postnatal development.
      Similarly, although neuronal atrophy was observed in aged autonomic ganglia, this
      was not a general phenomenon but was specific to neurons innervating particular
      target tissues. Sympathetic neurons innervating the middle cerebral artery showed
      significant axonal and dendritic atrophy in old age, whereas neurons innervating
      the iris were morphologically unchanged. The trophic influence of peripheral
      target tissues on their innervating neurons has been shown to decline in old age
      possibly as a result of decreased availability of target-derived neurotrophic
      factors such as nerve growth factor (NGF) [Gavazzi et al. (1992) Neuroreport,
      3:717-720]. Therefore, in an attempt to reverse neuronal atrophy where it
      occurred, NGF was infused via miniosmotic pumps over the peripheral axons of aged
      neurons. NGF induced increases in soma size, dendritic length and axonal
      arborization. However, in contrast to young adult neurons, no increase in the
      number of dendritic branch points or primary dendrites was observed, suggesting
      that some aspects of neuronal plasticity are impaired in old age. In sum, these
      results show a range of age- and target-specific differences in the axonal and
      dendritic morphology of autonomic neurons that may result from differing trophic
      interactions with their target tissues.

PMID- 8873056
TI  - Histochemical detection of age- and injury-related changes in signal transduction
      in the superior cervical ganglion.
AB  - The superior cervical ganglion (SCG) is thought to be a good model for
      correlation studies of morphology, function and metabolism of neurons. The SCG
      has a relatively simple organization, it can be easily manipulated in situ, and
      it maintains synaptic transmission and a high metabolic rate during in vitro
      incubations. The histology and structure of SCG neurons have been characterized
      in detail, and physiologic stimuli, injury and aging have all been found to
      induce changes in the SCG morphology. During the last decade, research in the
      field of signal transduction has greatly expanded. Several signal transduction
      pathways have been identified that participate in the regulation of
      neurotransmitter synthesis, gene expression, neuronal excitability and growth
      factor responses of sympathetic neurons. We have been interested in using the SCG
      to study some of the second and third messengers involved in converting external
      stimuli received by sympathetic neurons into cellular short- and long-term
      events. Using immunohistochemistry, we have investigated protein kinase C
      subtypes and the immediate early gene product Fos in the SCG, and characterized
      some of the changes induced by injury and aging in these messenger molecules. We
      will review the results and discuss the advantages and disadvantages of using
      histological methods in the study of signal transduction in sympathetic neurons.

PMID- 8873057
TI  - Nitric oxide synthase in the autonomic and sensory ganglia innervating the
      submandibular salivary gland.
AB  - This article reviews the neuroanatomical studies on the distribution of nitric
      oxide synthase (NOS) in neurons and nerve fibers innervating the submandibular
      gland. Specificity of NADPH-diaphorase activity as a histochemical marker of
      neuronal NOS is discussed in light of corresponding NOS immunoreactivity.
      Anatomical data suggest that nitric oxide may affect neural regulation of the
      submandibular gland through both sympathetic, parasympathetic and sensory
      divisions of the autonomic nervous system. NOS-containing nerve terminals in the
      gland parenchyme are mainly vascular and either parasympathetic and/or sensory in
      nature, while sympathetic terminals lack NOS. Most postganglionic parasympathetic
      neurons are intensely NOS-immunoreactive. Some of the preganglionic
      parasympathetic neurons show vague reactivity, while their terminals in the
      submandibular ganglia stain heavily. The postganglionic sympathetic neurons
      normally show only barely visible reactivity, while manipulations interrupting
      axonal continuity increase neuronal NOS content. A subpopulation of the
      preganglionic sympathetic neurons and their terminals are intensely reactive. The
      observations summarized here suggest that nitric oxide participates in the
      control of blood flow through the gland, while direct effect on secretion is
      unlikely.

PMID- 8873058
TI  - Localization, regulation and functions of neurotransmitters and neuromodulators
      in cervical sympathetic ganglia.
AB  - Cervical sympathetic ganglia represent a suitable model for studying the
      establishment and plasticity of neurochemical organization in the nervous system
      since sympathetic postganglionic neurons: (1) express several neuromediators,
      i.e., short acting transmitters, neuropeptide modulators and radicals, in
      different combinations; (2) receive synaptic input from a limited number of
      morphologically and neurochemically well-defined neuron populations in the
      central and peripheral nervous systems (anterograde influence on phenotype); (3)
      can be classified morphologically and neurochemically by the target they
      innervate (retrograde influence on phenotype); (4) regenerate readily, making it
      possible to study changes in neuromediator content after axonal lesion and their
      possible influence on peripheral nerve regeneration; (5) can be maintained in
      vitro in order to investigate effects of soluble factors as well as of membrane
      bound molecules on neuromediator expression; and (6) are easily accessible.
      Acetylcholine and noradrenaline, as well as neuropeptides and the recently
      discovered radical, nitric oxide, are discussed with respect to their
      localization and possible functions in the mammalian superior cervical and
      cervicothoracic (stellate) paravertebral ganglia. Furthermore, mechanisms
      regulating transmitter synthesis in sympathetic neurons in vivo and in vitro,
      such as soluble factors, cell contact or electrical activity, are summarized,
      since modulation of transmitter synthesis, release and metabolism plays a key
      role in the neuronal response to environmental influences.

PMID- 8873060
TI  - Cardiac neurones of autonomic ganglia.
AB  - The properties of the postganglionic sympathetic neurones supplying the heart and
      arising in the stellate and adjacent paravertebral ganglia of various species are
      discussed with respect to their location, morphology, synaptic input and membrane
      characteristics. Results from our laboratory on the morphology of rat stellate
      neurones projecting to the heart were obtained either by intracellular injection
      of hexammine cobaltic (III) chloride or by retrograde labelling of cells using
      cobalt-lysine complex. Intracellular recordings were made from cells using
      electrodes filled either with potassium chloride plus hexammine cobaltic chloride
      or potassium acetate. Neurones which projected axons into cardiac nerve branches
      arising from the stellate ganglion were termed putative cardiac neurones, because
      of the possibility that some supply pulmonary targets. Putative cardiac neurones
      had unbranched axons and were ovoid or polygonal in shape, but showed
      considerable variation in soma size and in the complexity of dendritic trees. The
      mean two-dimensional surface area was 463 microns2 and the mean number of primary
      dendrites was seven. Other studies have found that the morphology of rat stellate
      ganglion neurones is similar to that of superior cervical ganglion cells.
      However, in strains of rat displaying spontaneous hypertension, dendritic length
      may be increased. Histochemical studies do not, as yet, seem to have demonstrated
      a distinctive neurochemical profile for stellate cardiac neurones, but various
      types of peptide-containing intraganglionic nerve fibres have been identified in
      the guinea pig. In our electrophysiological studies, putative cardiac neurones
      were found to receive a complex presynaptic input arising from the caudal
      sympathetic trunk and from T1 and T2 thoracic rami. In addition, 16% of cardiac
      neurones received a synaptic input from the cardiac nerve. The properties of
      postganglionic parasympathetic neurones distributed in the cardiac plexus and
      termed intrinsic cardiac neurones are discussed, including the results of studies
      on cultures of these neurones.

PMID- 8873061
TI  - Interaction between parasympathetic and sympathetic nerves in prevertebral
      ganglia: morphological evidence for vagal efferent innervation of ganglion cells
      in the rat.
AB  - Vagal efferent preganglionic neurons were anterogradely labeled by injecting
      either DiI or DiA, fluorescent lipophilic carbocyanine dyes, into the dorsal
      motor nucleus of the vagus of the rat. All neurons of the peripheral nervous
      system (outside the blood-brain barrier) were then fluorescently counterstained
      in vivo by injecting Fluorogold (Fluorochrome, Inc., Englewood, CO)
      intraperitoneally. The upper abdominal prevertebral ganglia, including the
      numerous microganglia associated with the periarterial plexuses of the celiac and
      superior mesenteric arteries, were identified and dissected in formalin-fixed
      tissue under ultraviolet light and stereomicroscopic guidance. In 14 of 15
      animals analyzed (93%), labeled vagal efferent fibers were found to penetrate
      into both the left and right celiac ganglia and the superior mesenteric ganglion,
      as well as into some of the associated microganglia. These projections formed
      varicose terminal-like structures, highly suggestive of synaptic contacts
      surrounding individual ganglion cells. In about half the animals, such vagal
      innervation was also seen in the left and right suprarenal ganglia. The
      specificity of vagal efferent labeling was confirmed by control experiments,
      which included injections in vagotomized animals and direct selective labeling of
      vagal afferents from the nodose ganglia. It is concluded that vagal efferent
      preganglionics innervate principal ganglion cells of prevertebral ganglia. These
      vagal contacts may either directly modulate the postganglionic outflow or else
      gate some or all of the potential modulatory inputs to these postganglionic
      neurons, thus allowing the vagal system to exert a more selective influence on
      sympathetic outflow. Finally, the use of laser scanning confocal microscopy and
      the in toto Fluorogold staining method for investigations of the peripheral
      nervous system are discussed.

PMID- 8873062
TI  - Collagen fibril surface: TMAFM, FEG-SEM and freeze-etching observations.
AB  - Native, unfixed collagen fibrils from rat tail tendon were dehydrated following
      different procedures and observed under a FEG-SEM and an AFM operated in Tapping
      Mode (TMAFM). Freeze-etched, untreated fibrils from the same tissue were also
      observed for comparison. The most notable features of the fibril surface, i.e.,
      the gap/overlap alternation and three prominent intraperiod ridges, were
      simultaneously visible only in freeze-etched specimens, while under the SEM and
      the TMAFM their appearance was dependent on both the dehydration procedure and
      the visualization technique. The different susceptibility of the collagen fibril
      surface structures to various treatments clearly implies the existence of domains
      of different composition. Moreover, identical specimens were imaged differently
      by SEM and TMAFM, highlighting instrument-specific advantages and limitations.
      The onset of dehydration-dependent, procedure-specific artifacts should be
      considered in high-resolution studies of connective tissues. As for any
      biological specimen, the final aspect of collagen fibrils is determined no less
      by the preliminary treatments than by the visualization approach.

PMID- 8873063
TI  - Two distinct forms of USF in the Lytechinus sea urchin embryo do not play a role
      in LpS1 gene inactivation upon disruption of the extracellular matrix.
AB  - Recent studies in our laboratory indicated that the upstream stimulatory factor
      (USF) in the sea urchin embryo of Lytechinus acts as a transcriptional repressor
      for the aboral ectoderm-specific expression of the LpS1 genes. Disruption of the
      extracellular matrix (ECM) arrests development prior to gastrulation and
      inactivates the LpS1 genes. We wanted to determine whether the inactivation of
      the LpS1 genes by ECM disruption may be due to an increase in USF expression. In
      the course of the investigation, a second L, variegatus USF cDNA clone (LvUSF2)
      was isolated and sequenced. The deduced amino acid sequence of LvUSF2 is nearly
      identical to LvUSF1 except at the amino end, where they are sharply divergent.
      Like LvUSF1, LvUSF2 has a USF-specific, a basic/hefixloop-helix, and a leucine
      zipper domain. Genomic DNA blots indicated that the two cDNA clones are derived
      from one gene, which suggested that the Lytechinus USF1 and USF2 mRNAs, of
      approximately 6.0 and 4.0 kb, respectively, are the result of differential RNA
      splicing. ECM disruption in Lytechinus embryos caused a relative drop in USF RNA
      accumulation levels to approximately 60% of control embryos, while LpS1 RNA
      accumulation levels dropped to less than 5%. USF protein levels and DNA binding
      activities in ECM-disrupted embryos also dropped to approximately 60% to that of
      control embryos. A mutation at the USF binding site in an LpS1 promoter
      chloramphenicol acetyl transferase (CAT) fusion DNA construct did not cause a
      relative increase in CAT activity in ECM disrupted embryos. These results suggest
      that the induced drop in LpS1 gene expression by ECM disruption is not due to an
      increase in the repressive activity of USF.

PMID- 8873064
TI  - Transcription and translation of the outer dense fiber gene (Odf1) during
      spermiogenesis in the rat. A study by in situ analyses and polysome
      fractionation.
AB  - Transcription and translation of the Odf1 gene encoding the major protein of
      sperm tail outer dense fibers has been investigated in rat spermatogenesis. Odf1
      mRNA was detected by in situ hybridization from step 6 round spermatids up to
      step 17. The protein was detected immunohistochemically in the cytoplasm of step
      7 spermatids up to step 18 and in the sperm tails. The distribution of Odf1 mRNA
      and the respective transcript sizes in polysomes and translationally inactive
      nonpolysomal ribonucleoprotein particles has been investigated by fractionation
      on sucrose gradients and Northern blot analysis of the isolated RNA. In adult rat
      testis about 30% of Odf1 mRNA is associated with the polysomal fraction, but the
      bulk is stored in translationally inactive ribonucleoprotein particles. In 35-day
      old rat testis, in which spermatids have reached step 15 of spermiogenesis, only
      about 10% of Odf1 mRNA can be found in the polysomal fraction. It seems
      therefore, that translation of Odf1 is greatly enhanced in the maturation phase
      of spermiogenesis during which a marked increase in diameter of outer dense
      fibers takes place. In the polysomal fraction, Odf1 transcripts are of
      heterogeneous size. Northern blot analysis of fractionated RNA digested with
      RHaseH revealed the presence of both Odf1 transcripts (Burfeind and Hoyer-Fender,
      1991: Dev Biol 148: 195-204; Burfeind et al., 1993: Eur J Biochem 216: 497-505)
      on polysomes. While the larger transcript population is heterogeneous in size due
      to variable polyA-shortening, the smaller transcript population is not
      deadenylated compared to those present in nonpolysomal fractions.

PMID- 8873065
TI  - Estrogenic effect on the expression of estrogen receptor, COUP-TF, and
      lactoferrin mRNA in developing mouse tissues.
AB  - We have previously demonstrated that lactoferrin (LF) is a major estrogen
      inducible protein in the mouse uterus. The increase of LF mRNA after estrogen
      treatment (> 300 fold) is the result of a complex interplay among transcription
      factors acting on the estrogen response element (ERE) of the LF gene. Two
      transcription factors-the estrogen receptor (ER) and the chicken ovalbumin
      upstream promoter transcription factor (COUP-TF)-play opposing roles in the
      estrogen responsiveness of the LF gene promoter-reporter constructs in
      transiently transfected human endometrial carcinoma cells. The ratio of ER/COUP
      TF in the transfected cells appears to be critical for estrogen-stimulated LF
      gene promoter activity (Liu et al, 1993). In the current study, ER and COUP-TF
      mRNA levels are examined and related to LF mRNA expression in various mouse
      tissues, including the developing uterus with/without estrogen stimulation.
      Results show that LF mRNA and protein are expressed in various tissues during
      development, but the potent synthetic estrogen, diethylstilbestrol (DES), does
      not increase LF mRNA expression in nonreproductive tissues such as liver, spleen,
      and lung. In contrast, in developing neonatal reproductive tract tissues, DES
      increases LF mRNA and protein expression as previously reported in immature and
      mature uterine tissues. DES, however, did not affect ER and COUP-TF expression in
      developing uterine tissues. Although the uterus has a high ratio of ER/COUP-TF as
      compared to other tissues examined, COUP-TF may not be the only regulator for LF
      gene expression in this particular tissue since COUP-TF remains constant during
      development and following DES treatment. These data point to the complexity of
      differential expression of LF gene in estrogen responsive and nonresponsive
      tissues during development.

PMID- 8873066
TI  - Maternal age effect on early human embryonic development and blastocyst
      formation.
AB  - In humans, age-related decline in female fertility can be explained by a
      reduction in quality either of the older uterus or of the embryos arising from
      aging oocytes. The aim of this study was to examine the latter hypothesis, using
      in vitro fertilization (I.V.F.) and coculture of embryos until the blastocyst
      stage. We determined the blastocyst formation rate ([blastocysts/embryos on day
      2]* 100) and the blastocyst expansion rate ([expanded blastocysts/blastocysts]*
      100) according to the patient's age the day of I.V.F. With increase in age, the
      number of retrieved oocytes decreased, without alteration of the cleavage rate.
      In patients above age 30 years, preimplantation development to blastocysts
      declined due to an increase in embryo arrest at the morula stage. If blastocyst
      stage was reached, a negative linear relationship between blastocyst expansion
      rate and patient age was observed. Drops in gamete production and embryo
      development with increasing age led to a drastic decrease in patients having at
      least one expanded blastocyst (< 30 years, 82%; > or = 40 years, 36%). A high
      delivery rate per oocyte retrieval (25.8%) was observed in patients above age 40
      years after embryo transfer at the blastocyst stage. These results give a clear
      indication of decline in the quality of human embryos arising from aging oocytes.
      The origin of this alteration is discussed in terms of chromosome abnormalities,
      role of maternally-inherited products from the oocyte, timing of genomic
      activation, and temporal pattern of gene expression during initial development of
      the human embryo.

PMID- 8873067
TI  - Characterization of DNA synthesis during the 2-cell stage and the production of
      tetraploid chimeric pig embryos.
AB  - The DNA content of nuclei during the 2-cell stage as well as in presumptive
      tetraploid embryos was investigated. In vivo produced pig zygotes were cultured
      to the 2-cell stage and either monitored for cleavage to the 4-cell stage or
      mounted at various times post-cleavage and DNA content determined. The length of
      the 2-cell stage was 14.8 +/- 3.0 hr. There was a significant increase in the
      length of the 2-cell stage due to the time in vitro as a zygote (P < 0.001: R2 =
      0.866). The DNA content increased (P < 0.05) each 2 hr postcleavage until 10 hr
      postcleavage. This suggested that there is a short G1 and G2 phase and a
      relatively long phase of DNA synthesis. Next, 2-cell stage embryos were pulsed
      with electricity to induce cell-to-cell fusion. Whereas only about half fused
      within 30 min (55%), most (96%) developed to the blastocyst stage. The DNA
      content of the nuclei of the embryos was consistent with them being tetraploid. A
      final experiment was designed to evaluate the ability of the tetraploid embryo to
      form a chimera with isolated inner cell mass (ICM) cells. Inner cell masses were
      isolated from d 6 embryos, cut into thirds, labeled with DiO (a membrane die) and
      injected into the perivitelline space of 4-cell-stage tetraploid embryos. Twelve
      of 17 formed blastocysts. In most (8/12), the ICM of the resulting blastocyst was
      labeled, whereas in one the only fluorescence was in the trophectoderm, and in
      two fluorescence was evenly distributed between the ICM and trophectoderm. These
      results suggest that it may be possible to create a fetus derived from ICM cells,
      or potentially stem cells, that has a tetraploid trophoblast.

PMID- 8873068
TI  - Effect of streptozotocin-induced diabetes on phosphodiesterase activity in rat
      luteal cells.
AB  - The present studies were carried out to characterize the cAMP-phosphodiesterase
      enzyme (PDE) in luteal cells recovered from pseudopregnant rats with
      streptozotocin-induced diabetes. A significant increase in the specific activity
      of the enzyme was detected in luteal cells from diabetic rats (Group D) with
      respect to control rats (Group C). This increase could not be prevented by
      insulin therapy (Group I). Luteal cells from Groups C and D rats responded in
      vitro to insulin by increasing their PDE activity (% of stimulus of specific
      activity: C = 75%, D = 110%). However, in cells isolated from Group I, the
      hormone caused an inhibition of PDE activity (% of inhibition of specific
      activity: 48%). When cytosolic fractions from Groups C, D and I were submitted to
      ion exchange chromatography, two PDE activity peaks could be observed and the
      activity of the different fractions was increased in the presence of Ca2+ and
      calmodulin. Nevertheless, the Ca(2+)-calmodulin effect was much lower in the
      extracts from Groups D and I than for controls. Kinetic studies of luteal PDE
      showed nonlinear Lineweaver-Burk graphs with two apparent ATP hydrolysis sites.
      Similar K(m) values were found for PDE from groups C, D, and I, whereas the Vmax2
      for the enzyme was higher in Groups D and I. The endogenous concentration of
      cAMP, measured by RIA, showed no significant differences among Groups C, D, and
      I. On the basis of these results, we conclude that the specific activity of PDE
      is significantly increased in luteal cells from streptozotocin-induced diabetic
      animals, which could explain the previously described reduction in LH-stimulated
      progesterone production by luteal cells in diabetic rats.

PMID- 8873069
TI  - Local and systemic alterations in cyclic 3',5' AMP phosphodiesterase activity in
      relation to tail regeneration under hypothyroidism and T4 replacement in the
      lizard, Mabuya carinata.
AB  - To establish the relationship between thyroid hormone and cyclic Adenosine
      monophosphate (cAMP) during lacertilian tail regeneration, cAMP
      phosphodiesterase, the hydrolytic enzyme of cAMP, was assayed in the tail
      regenerate, liver, and skeletal muscle of control (group A), chemically
      thyroidectomized (group B), and thyroidectomized and T4-replaced (group C)
      animals during various periods of tail regeneration. Enzyme activity was elevated
      in all three tissues of group B animals. Animals of group C showed an
      intermediate level of enzyme activity between controls (group A) and experimental
      animals (group B). These observations suggest a possible regulatory role of
      thyroxine in maintaining optimum levels of phosphodiesterase. The retardation in
      regeneration observable in the hypothyroid group of animals may be correlated
      with low levels of tissue cAMP. However, the operation of other influencing
      factors on phosphodiesterase during regeneration can be surmised from the
      observed tendency to exhibit similar patterns of phase-specific modulations in
      enzyme activity. Our observations are discussed in terms of phase-specific
      involvement of cAMP in regeneration, as well as its role in other metabolic
      aspects and the possible mode of indirect control exerted by thyroxine on
      lacertilian tail regeneration.

PMID- 8873070
TI  - Intracellular pH change does not accompany egg activation in the mouse.
AB  - In the sea urchin, some other marine invertebrates, and the frog, Xenopus, egg
      activation at fertilization is accompanied by an increase in intracellular pH
      (pHi). We measured pHi in germinal vesicle (GV)-intact mouse oocytes, ovulated
      eggs, and in vivo fertilized zygotes using the pH indicator dye, SNARF-1. The
      mean pH, was 6.96 +/- 0.004 (+/- SEM) in GV-intact oocytes, 7.00 +/- 0.01 in
      ovulated, unfertilized eggs, and 7.02 +/- 0.01 in fertilized zygotes, indicating
      no sustained changes in pHi after germinal vesicle breakdown (GVBD) or
      fertilization. To examine whether transient changes in pHi occur shortly after
      egg activation, mouse eggs were parthenogenetically activated by 7% ethanol in
      phosphate buffered saline (PBS); no significant change in pHi followed ethanol
      activation. Since increased Na+/H+ antiporter activity is responsible for pHi
      increase in the sea urchin, pHi was measured in the absence of added bicarbonate
      or CO2 (a condition under which the antiporter would be the only major pHi
      regulatory mechanism able to operate, since the others were bicarbonate
      dependent) in GV-intact oocytes, ovulated eggs, and in vivo fertilized zygotes to
      determine whether a Na+/H+ antiporter was activated. There was no physiologically
      significant difference in pHi after GVBD or fertilization, when pHi was measured
      in bicarbonate-free medium, nor any change upon parthenogenetic activation. Thus,
      a change in pHi is not a feature of egg activation in the mouse.

PMID- 8873071
TI  - Expression and localization of DNA topoisomerase II during rat spermatogenesis.
AB  - The potential role(s) of DNA topoisomerase II (topo II) during chromatin changes
      that characterize different stages of spermatogenesis was investigated in the rat
      by an analysis of the expression and localization of topo II mRNA and protein in
      individual spermatogenic cells. Expression of topo II was restricted to
      spermatogonia, spermatocytes, and round and early-elongating spermatids. Two
      protein bands of 177 and 170 kDa were detected in immunoblots of spermatocytes
      and round spermatids, while bands of 148 and 142 kDa were prominent in
      preparations of elongating spermatids. Topo II levels and distribution patterns,
      as observed by immuno-fluorescent microscopy, exhibited cell type-specific
      variations. Differences in topo II staining patterns were also apparent when
      nuclear matrices of spermatogenic cells were prepared with different extraction
      conditions. In addition to its possible function as a structural component, topo
      II, associated with nuclear matrix preparations from spermatogenic cells,
      possessed catalytic activity. These observations indicate that both the 177 and
      170 kDa and the 148 and 142 kDa forms of topo II share similar structural and
      functional properties. Topo II beta mRNA was transcribed in rat spermatogenic
      cells at 6.2 kb. Relative levels of topo II beta mRNA were high in spermatogonia
      and spermatocytes, and decreased in both round and early-elongating spermatids.
      Changes in topo II expression levels and localization patterns represent distinct
      stage-specific markers for the maturation of spermatogenic cells, and are
      consistent with the involvement of topo II in mediating DNA modifications and
      chromatin changes during spermatogenesis.

PMID- 8873072
TI  - Characterization of acrosin-like activity of lake sturgeon (Acipenser fulvescens)
      spermatozoa.
AB  - Acipenserid fish sperm possess trypsin-like activity, resembling acrosin activity
      of mammalian sperm, which can be measured by hydrolysis of N-alpha-benzoyl-DL
      arginine p-nitroanilide (BAPNA) (Ciereszko et al., 1994: J Exp Zool 268:486-491).
      We found that this activity can be preserved when sperm is frozen on dry ice with
      0.6 M sucrose-10% dimethylsulfoxide (DMSO) extender (sperm:extender ratio 1:3),
      and subsequently stored in liquid nitrogen. However, other methods of freezing
      (without cryoprotectant at -18 degrees C, -80 degrees C, and -196 degrees C) did
      not protect this activity. Acrosin-like activity decreased in the course of
      storage of milt on ice; 88% decline was recorded after 13 days. Acrosin-like
      activity increased with temperature from 10 degrees C to 30 degrees C, but was
      inactivated at 40 degrees C to about 40% as compared to the optimum temperature.
      Triton X-100 inhibited activity by 15% and 72% at 0.01% and 0.1% concentrations,
      respectively. Activity was not affected by Mg2+ but was inhibited by Zn2+ (30%
      and 75% in the presence of 0.1 mM and 1 mM, respectively). Maximum velocity of
      substrate hydrolysis was observed at 2 mM of BAPNA. Acrosin-like activity was
      effectively inhibited by 4'-acetamidophenyl 4-guanidinobenzoate (AGB), an
      inhibitor of mammalian acrosin. Sperm acrosin-like activity correlated negatively
      with antiproteinase activity of seminal plasma. We conclude that sturgeon acrosin
      like activity shares many properties with mammalian acrosin. On the other hand,
      it has some unique properties which may represent adaptations of this enzyme to
      the environment of external fertilization.

PMID- 8873073
TI  - Comparative patterns of protein phosphorylation during activation of surf clam
      oocytes by different artificial agents.
AB  - Oocytes from the surf clam Spisula solidissima are arrested at prophase I of
      meiotic maturation, until fertilization, We analyzed the patterns of
      phosphorylated proteins under procedures mimicking, to various degrees, the
      normal sperm-induced activation process. High K(+)-seawater, the phorbol ester
      TPA, serotonin, or a combination of these were used to analyze their effects on
      both germinal vesicle breakdown (GVBD) and protein phosphorylation. Oocytes were
      preloaded with 35S-methionine or 32P-phosphate, and the pattern of labeled
      proteins was analyzed by polyacrylamide gel electrophoresis followed by
      autoradiography. When comparing, in high K(+)-activated oocytes, the pattern of
      phosphorylated proteins with that of synthesized proteins, it appeared that these
      two processes were largely unrelated to one another. Activation induced by TPA
      was slower (60 min for GVBD) than that induced by high K+ or serotonin (12-15 min
      for GVBD), but was similarly sensitive to the protein phosphorylation inhibitor,
      6-dimethylaminopurine, and resulted in a qualitatively similar pattern of
      phosphorylated proteins appearing with slower kinetics, reflecting slower GVBD.
      When both serotonin and TPA were added to oocytes, the kinetics of GVBD was
      intermediate (30 min), and so was the appearance of phosphorylated proteins.
      Finally, the kinetics of development of H1 kinase activities was evaluated in
      oocytes activated by serotonin, TPA, or both. Similar to the general pattern of
      phosphorylated proteins, increased histone H1 kinase activities developed to
      similar degrees but with kinetics reflecting those of GVBD in each case. In
      conclusion, activations by different artificial agents, utilizing different
      pathways, resulted in GVBD with different kinetics but similar overall patterns
      of phosphorylated proteins after a lag typical of the agent used. This suggests
      that diverse pathways may initially be used to activate oocytes, but that these
      different pathways eventually merge into a common one, resulting in a highly
      conserved and regulated sequence of phosphorylation processes.

PMID- 8873074
TI  - Extent of sperm chromatin hydration determined by atomic force microscopy.
AB  - Volume measurements were performed on intact bull and mouse sperm heads and
      amembranous sperm nuclei, both in the fully hydrated (fluid cell) and dehydrated
      (air-dried on glass coverslips) states by atomic force microscopy (AFM). Data
      were obtained by analyzing a small population of cells/nuclei, as well as by
      performing repeated measurements on single cells imaged following the addition of
      increasing concentrations of propanol. Results show that the volume of fully
      hydrated, intact sperm heads and amembranous sperm chromatin particles are at
      least twice the volume of their air-dried counterparts. Dehydration occurs
      rapidly in air, and the reduction in volume of chromatin induced by water loss
      appears to be completely reversible. These studies demonstrate that both mouse
      and bull sperm chromatin are extensively hydrated in the native state, and are
      not as compact as previous studies have suggested.

PMID- 8873075
TI  - Sak 57, an intermediate filament keratin present in intercellular bridges of rat
      primary spermatocytes.
AB  - We have previously reported the purification of Sak 57 (for spermatogenic
      cell/sperm-associated keratin of molecular mass 57 kDa) from outer dense fibers
      of rat sperm tails. Internal protein sequence analysis of Sak 57 revealed 70-100%
      homology to the 1A and 2A regions of the alpha-helical rod domain of human,
      mouse, and rat keratins. A multiple antigen peptide was synthesized using the
      KQYEDIAQK sequence corresponding to the 2A region and a polyclonal antibody was
      produced in rabbit to detect Sak 57. During spermiogenesis, Sak 57 associates
      with the microtubular manchette before becoming a component of para-axonemal
      keratin structures of the developing tail. We now report that during late meiotic
      prophase, intercellular bridges linking late pachytene-diplotene spermatocytes
      display a distinct ribbon containing a Sak 57/beta-tubulin complex, separated by
      a nonimmunoreactive midzone. Indirect immunofluorescence demonstrates that the
      ribbon is the final stage of a three-step developmental sequence: (1) a
      spindlelike arrangement radiating from equidistant spherical centers in early
      pachytene spermatocytes, (2) an ectoplasmic shell-like framework in mid-to-late
      pachytene spermatocytes, and (3) a Sak 57/beta-tubulin-containing ribbon found in
      intercellular bridges linking adjacent late pachytene-diplotene spermatocytes.
      Shear forces causing a breakdown of one of the conjoined spermatocytes do not
      disrupt the cytoskeletal ribbon. Results of this work, together with previous
      observations during spermiogenesis, show that Sak 57 associates with cytoplasmic
      microtubules in a timely fashion. Upon completion of late meiotic prophase, the
      Sak 57/microtubule complex behaves as an intercellular ligament and contributes
      to both the strength of intercellular bridges and the cohesiveness of members of
      a spermatocyte lineage.

PMID- 8873076
TI  - Special issue dedicated to Dr. Hans Thoenen.

PMID- 8873077
TI  - Neurotrophins and the primate central nervous system: a minireview.
AB  - The central nervous system (CNS) of primates is more complex than the CNS of
      other mammals. Details of the development and aging of the primate CNS have
      recently been revealed by various neurobiological techniques. It has become clear
      that the primate CNS has unique characteristics, for example, the capacity for
      the overproduction and elimination of fibers and synapses. Some differences have
      also been found in the distribution of and changes with development in levels of
      various neuroactive substances. Recent discoveries of a variety of neurotrophins
      in the mammalian CNS have led to research on the neurobiology of these molecules
      in the primate CNS. The distribution of and changes with development in levels of
      nerve growth factor (NGF) in the primate CNS are closely correlated with the
      cholinergic system of the basal forebrain. The administration of NGF into the
      monkey brain prevents the degeneration of the cholinergic neurons of the basal
      forebrain after axotomy, a result that suggests that neurotrophins might be very
      valuable agents for the future treatment of neurological diseases, such as
      Alzheimer's and Parkinson's diseases.

PMID- 8873078
TI  - Paracrine and autocrine actions of neurotrophic factors.
AB  - Neurotrophic factors are proteins that promote the survival and growth of neurons
      in the vertebrate nervous system. Although it is well known that many neurons
      obtain these factors from the regions to which their axons project, studies of
      the sites of neurotrophic factor synthesis have raised the possibility that at
      least some neurons may obtain these factors from other sources. Alternative
      sources of neurotrophic factors include cells along a neuron's axon shaft and
      cells or other axons terminals within the vicinity of a neuron's cell body and
      dendritic arbour. In addition, recent experimental studies have shown that at
      certain stages of development neurotrophic factor autocrine loops operate in some
      neurons. The evidence for and the potential physiological significance of these
      different modes of action of neurotrophic factors will be discussed.

PMID- 8873079
TI  - Molecules inhibiting neurite growth: a minireview.
AB  - Molecules and activities which repulse growing neurites or induce growth cone
      collapse and long-lasting growth inhibition have been defined over the last 10
      years. Recently, specific guidance roles for developing axons and pathways could
      be associated with such repulsive effects. A high molecular weight membrane
      protein located in CNS myelin acts as potent neurite growth inhibitor and may
      play a role as a negative control element for sprouting, neurite growth and
      regeneration, and for the plasticity of the adult CNS. Interestingly, some
      guidance molecules can have positive, growth-promoting as well as negative,
      repulsive effects for specific types of neurons. These results underline the
      complex mechanisms involved in neurite guidance which depends on the
      interpretation of combinations of incoming signals by particular growth cones.

PMID- 8873080
TI  - Neurotrophin-4/5 treatment reduces infarct size in rats with middle cerebral
      artery occlusion.
AB  - The aim of this study was to determine whether neurotrophin-4/5 (NT-4/5)
      treatment alters infarction volume following permanent focal cerebral ischemia in
      the rat. Permanent focal cerebral ischemia was produced in adult male rats by
      intraluminal occlusion of the right middle cerebral artery. NT-4/5 was
      administered intraventricularly one day before and immediately following
      occlusion. Rats were sacrificed at 1, 4 and 7 days after occlusion. NT-4/5
      treatment reduced infarction volume by 34% when compared to control rats 1 day
      after occlusion. Infarction volume was unaltered by treatment 4 to 7 days after
      occlusion. Middle cerebral artery occlusion led to a significant reduction in
      levels of mRNAs coding for catalytic and truncated TrkB receptors. This
      expression was unaffected by NT-4/5 treatment.

PMID- 8873081
TI  - The concept of uptake and retrograde transport of neurotrophic molecules during
      development: history and present status.
AB  - In the present review honoring Hans Thoenen's contributions to the concept of
      uptake and retrograde transport of trophic molecules, I have attempted to
      identify the major historical pathways that had to converge before this concept
      could be accepted as a fundamental principle in neurobiology. Some of the
      critical events in this history which are discussed here include: neuron-target
      interactions, bidirectional trophic signals, axoplasmic transport, receptor
      mediated endocytosis, transneuronal trophic signals, the discovery of NGF, the
      retrograde transport of NGF, and the production of NGF by target tissues. Only
      when all of these diverse pieces of the puzzle were in place was the concept
      finally confirmed as being the mechanism that mediates the many phenomena
      attributed to the regulation and maintenance of neurons by their targets.

PMID- 8873082
TI  - Signal transduction from membrane to nucleus: the special case for neurons.
AB  - Neurons have a unique problem with signal transduction from the membrane in the
      region of their terminals back to the cell body and nucleus. This distance may be
      several meters in some nerves in some species, so there is a requirement for some
      mechanism to stabilize the signal. This review examines two complementary
      mechanisms for this signal transduction, either by the retrograde axonal
      transport of the neurotrophic factor together with its receptor, or the transport
      of a stable activated second messenger molecule. Extrapolation of studies on the
      fibroblast signal transduction pathway, where it has been shown that G1 can
      translocate from the membrane to the nucleus, has led to the demonstration of the
      retrograde axonal transport of several putative signaling molecules. The alpha
      subunits of both G1 and Gz are retrogradely transported and Gz alpha or possibly
      the intact heterotrimeric Gz subsequently accumulates in dorsal root ganglia
      nuclei. Thus Gz1 Gi1 and potentially other G-proteins and distinct signaling
      molecules may provide additional signal transduction pathways to that of the
      neurotrophins from terminal to nucleus.

PMID- 8873083
TI  - Neurotrophin-4: the odd one out in the neurotrophin family.
AB  - Neurotrophin-4 (NT-4) is a member of a family of neurotrophic factors, the
      neurotrophins, that control survival and differentiation of vertebrate neurons (2
      4). Besides being the most recently discovered neurotrophin in mammals, and the
      least well understood, several aspects distinguish NT-4 from other members of the
      neurotrophin family. It is the most divergent member and, in contrast to the
      other neurotrophins, its expression is ubiquitous and appears to be less
      influenced by environmental signals. NT-4 seems to have the unique requirement of
      binding to the low-affinity neurotrophin receptor (p75LNGFR) for efficient
      signalling and retrograde transport in neurons. Moreover, while all other
      neurotrophin knock-outs have proven lethal during early postnatal development,
      mice deficient in NT-4 have so far only shown minor cellular deficits and develop
      normally to adulthood. Is NT-4 a recent addition to the neurotrophic factor
      repertoire in search of a crucial function, or is it an evolutionary relic, a
      kind of wisdom tooth of the neurotrophin family?

PMID- 8873084
TI  - Preparation of a cell-free translation system from PC12 cell.
AB  - The postmitochondrial fraction (S10) contains the cellular components essential
      for translation, and a high-salt wash (HSW) of the ribosomes is enriched in
      eukaryotic initiation factors. This report describes the preparation of a cell
      free translation system utilizing an S10 extract from PC12 cells. The products
      synthesized from either firefly luciferase mRNA or PC12 cell poly(A) RNAs in the
      PC12-S10 extract were increased by the addition of the HSW from PC12 cells.
      Increases in the translation of luciferase mRNA by the addition of PC12-HSW were
      dose-dependent and also dependent on the time of incubation. The translation of
      human epidermal growth factor receptor (hEGFR) mRNA could also be detected in the
      PC12-S10 extract translation system by immuno-precipitation. N-linked
      glycosylation of the translation products also was observed. The efficiency of
      translation was altered by the addition of Mg2- or K+, and optimization of the
      concentrations of these ions was necessary for each mRNA. The translation system
      made from PC12 cells, then, is capable of the synthesis of proteins of relatively
      high molecular weight and should be useful for analyzing mechanisms of
      translational control during proliferation and differentiation of cells from a
      neuronal lineage.

PMID- 8873085
TI  - Neurotrophin-3 and trkC-immunoreactive neurons in rat dorsal root ganglia
      correlate by distribution and morphology.
AB  - Previous studies have shown that a subpopulation of large dorsal root ganglion
      neurons contains neurotrophin-3 (NT3)-like immunoreactivity. It is not known,
      however, whether these NT3 immunoreactive neurons also express the high affinity
      receptor for NT3, trkC. In the present study, the distribution and morphology of
      trkC immunoreactive neurons have been correlated with those of NT3 immunoreactive
      neurons in the dorsal root ganglia. Size and segmental distributions of both
      antigens indicate that they are present in the same group of large sensory
      neurons. Almost twice the number of these neurons are present in the cervical and
      lumbar spinal ganglia than in the thoracic. Co-localization study indicates that
      94% of NT3 immunoreactive neurons express trkC. Our findings support the proposal
      that NT3 in these neurons is derived from their peripheral targets rather than
      synthesized in situ.

PMID- 8873086
TI  - EGF-induced sustained tyrosine phosphorylation and decreased rate of down
      regulation of EGF receptor in PC12h-R cells which show neuronal differentiation
      in response to EGF.
AB  - PC12h-R cell, a subclone of PC12 cells, exhibited a neuron-like phenotype,
      including neurite outgrowth and increased acetylcholinesterase activity, in
      response to epidermal growth factor (EGF) as well as nerve growth factor (NGF).
      We examined the mechanism by which EGF induced the neuronal differentiation in
      PC12h-R cells. The EGF-induced neuronal differentiation of PC12h-R cells was not
      blocked by K252a, whereas that induced by NGF was. EGF induced sustained tyrosine
      phosphorylation of the EGF receptor in PC12h-R cells, but not in the parent PC12h
      cells, which do not show neuronal differentiation in response to EGF. In
      addition, the rate of EGF-induced down-regulation of the EGF receptor in PC12h-R
      cells was decreased compared with that in PC12h cells. Furthermore, we found that
      the duration of EGF-induced tyrosine phosphorylation of the EGF receptor in PC12h
      R cells was similar to that of NGF-induced tyrosine phosphorylation of p140trkA
      in PC12h cells. The EGF-induced phosphorylation of the EGF receptor in PC12h
      cells was less sustained than that of p140trkA by NGF in PC12h cells. These
      findings suggested that the EGF-induced neuronal differentiation of PC12h-R cells
      is due to the sustained activation of the EGF receptor, resulting from the
      decreased down-regulation of the EGF receptor and that the duration of the
      receptor tyrosine kinase activity determines the cellular responses of PC12
      cells. We concluded that sustained activation of the receptor tyrosine kinase
      induces neuronal differentiation, although transient activation promotes
      proliferation of PC12 cells.

PMID- 8873087
TI  - The development of the noradrenergic transmitter phenotype in postganglionic
      sympathetic neurons.
AB  - Here we review recent data on molecular aspects of the differentiation of the
      noradrenergic neurotransmitter phenotype in postganglionic sympathetic neurons
      during avian and mammalian embryogenesis. By experimental manipulation of the
      chick embryo, it has been shown that neural tube and notochord are important for
      noradrenergic differentiation which occurs when migrating neural crest cells, the
      precursors of sympathetic ganglion cells, reach the dorsal aorta. Bone
      morphogenetic proteins expressed in the dorsal aorta before and during the time
      of noradrenergic differentiation are likely candidates for growth factors
      involved in induction of noradrenergic differentiation, in vivo. To analyze
      noradrenergic differentiation, enzymes of the noradrenaline bio-synthesis pathway
      and catecholamine stores have been used as differentiation markers. The molecules
      involved in neurotransmitter release which are as important for a functional
      noradrenergic neuron as those required for transmitter synthesis and storage are
      only recently being studied in this context. For a comprehensive view of the
      embryonic development of the noradrenergic neurotransmitter phenotype, it will be
      necessary to understand how the systems for synthesis, storage and release of
      noradrenaline are assembled during neuronal differentiation.

PMID- 8873089
TI  - Distinct modulatory actions of TGF-beta and LIF on neurotrophin-mediated survival
      of developing sensory neurons.
AB  - The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF), and neurotrophin-3 (NT-3) are important for the regulation of survival
      and differentiation of distinct, largely non-overlapping populations of embryonic
      sensory neurons. We show here that the multifunctional cytokine transforming
      growth factor-beta (TGF-beta) fails to maintain sensory neurons cultured from
      embryonic day (E) 8 chick dorsal root ganglia (DRG), although DRG neurons are
      immunoreactive for the TGF-beta receptor type II, which is essential for TGF-beta
      signaling. However, in combination with various concentrations of NT-3 and NT-4,
      but not NGF, TGF-beta 3 causes a further significant increase in neuron survival.
      In DRG cell cultures treated with NGF, NT-3, and NT-4, a neutralizing antibody to
      TGF-beta decreases neuron survival suggesting that endogenous TGF-beta in these
      cultures affects the efficacies of neurotrophins. Consistent with this notion and
      a modulatory role of TGF-beta in neurotrophin functions is the observation that
      TGF-beta 2 and -beta 3 immunoreactivities and TGF-beta 3 mRNA are located in
      embryonic chick DRG in close association with neurons from E5 onwards. We also
      show that leukemia inhibitory factor (LIF) significantly decreases NGF-mediated
      DRG neuron survival. Together, these data indicate that actions and efficacies of
      neurotrophins are under distinct control by TGF-beta and LIF in vitro, and
      possibly also in vivo.

PMID- 8873090
TI  - Constitutive phosphorylation of TrkC receptors in cultured cerebellar granule
      neurons might be responsible for the inability of NT-3 to increase neuronal
      survival and to activate p21 Ras.
AB  - The neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT
      3) are both expressed in developing cerebellum in addition to their tyrosine
      kinase receptors. TrkB and TrkC. In contrast to BDNF.NT-3 has only a negligible
      or a transient survival activity on cultured cerebellar granule neurons. The
      granule neurons however, express both TrkC and Trk B receptors which suggests a
      basic difference in signaling between BDNF and NT-3 in these neurons. Here we
      have studied whether this difference can be attributed to the presence of
      alternative TrkC receptor variants on the granule neurons and which signaling
      pathway is specifically activated by BDNF but not by NT-3 in these neurons. Using
      RT-PCR it was shown that the cerebellar granule neurons express the full length
      TrkC receptor, in addition to variant receptors containing small inserts in the
      receptor tyrosine kinase domain. There was no dramatic change in the relative
      amounts of different TrkC receptors during development. However, we found the
      TrkC receptor constitutively phosphorylated even in the absence of added ligand
      suggesting an interaction of TrkC with endogenously produced NT-3. In addition,
      NT-3 was able to phosphorylate the BDNF receptor, TrkB but only at higher
      concentration (50 ng/ml). There were also distinct differences in the activation
      of intracellular molecules by BDNF and NT-3. Thus, p21 Ras and PLC gamma were
      activated by BDNF but not by NT-3 whereas both BDNF and NT-3 increased calcium
      and c-fos mRNA in the granule neurons. These results show that differential
      activation of specific intracellular pathways such as that of p21 Ras determines
      the specific effects of BDNF and NT-3 on granule neuron survival. In addition,
      since calcium is increased by NT-3 in the cerebellar granule neurons, this
      neurotrophin might have some unknown important effects on these neurons.

PMID- 8873088
TI  - The response of motoneurons to neurotrophins.
AB  - The ongoing search for neurotrophic factors for motoneurons has led to the
      identification of a number of molecules which regulate motoneuron survival and
      function. Among these factors, the neurotrophins brain derived neurotrophic
      factor (BDNF), neurotrophin-3 (NT-3) and NT-4/5 but not nerve growth factor
      (NGF), can prevent embryonic and postnatal motoneuron cell death in a variety of
      experimental paradigms. Analysis of expression of p75, trkB and trkC-components
      of the neurotrophin receptors-supports a potential physiological role for these
      factors as muscle- and glial-derived trophic factors for motoneurons. However,
      the survival of motoneurons during embryonic development is not reduced in the
      absence of BDNF, NT-3 or NT-4, as revealed by gene knockout experiments. This
      points to the involvement of additional trophic factors in the regulation of
      embryonic and postnatal motoneuron survival. The purpose of this review is to
      bring together the often prophetic observations from earlier studies-prior to the
      identification and characterization of these neurotrophins-with more recent
      results.

PMID- 8873092
TI  - Cerebral vascular anatomy.
AB  - The angiographic anatomy of the vascular supply to the brain is described.
      Commonly seen anatomic variants are discussed. Venous anatomy and its importance
      in the pathophysiology of certain disease states also are described.

PMID- 8873091
TI  - Expression of neuronal-NOS in developing basal forebrain cholinergic neurons:
      regulation by NGF.
AB  - Nerve growth factor (NGF) acts through the receptor tyrosine kinase trkA to serve
      as a trophic factor for cholinergic neurons in the medial septal nucleus and
      vertical limb of the diagonal band. We have previously shown that the neuronal
      isoform of nitric oxide synthase (NOS) is selectively expressed in a large
      fraction of trkA-expressing cholinergic neurons in these brain regions in the
      adult rat, and that NGF induces the expression of neuronal-NOS in these cells.
      Herein, we show that: 1) neuronal-NOS is also localized to these neurons in the
      developing septum; 2) the expression of neuronal-NOS is regulated in the
      developing medial septal nucleus and vertical limb of the diagonal band; 3)
      neuronal-NOS regulation parallels that for other markers of basal forebrain
      cholinergic neuron differentiation, such as cholineacetyltransferase; and 4) NGF
      infusion in the postnatal period induces robust increases in neuronal-NOS mRNA
      and in NOS activity in the basal forebrain. Taken together with earlier findings,
      our results suggest that neuronal-NOS has a role in the differentiation and
      mature function of septal cholinergic neurons. Through enhancing neuronal-NOS
      synthesis, endogenous NGF is likely to regulate NO functions in vivo.

PMID- 8873093
TI  - Angiography and the evaluation of cerebrovascular disease in childhood.
AB  - This article outlines indications and techniques for and findings on angiography
      in pediatric cerebrovascular disease. The clinical entities described and
      illustrated include extracranial and intracranial pediatric vascular anomalies
      (hemangiomas and vascular malformations), pediatric aneurysms and occlusive
      cerebrovascular disease. Features specific to or more common in children are
      emphasized.

PMID- 8873094
TI  - Vertebrospinal angiography in the evaluation of vertebral and spinal cord
      disease.
AB  - Spinal angiography is an infrequently performed radiologic procedure requiring
      much skill and knowledge for its proper application. Most commonly, spinal
      angiography is used in the diagnosis of spinal arteriovenous malformations and in
      the delineation of vascular tumors of the spinal cord. Less usual indications may
      include preoperative evaluation of the spinal cord vasculature prior to surgeries
      involving the descending thoracic aorta or ventrolateral approaches to the spine,
      particularly in patients undergoing repeat operations. Spinal angiography should
      address three crucial considerations for the surgeon or neurointerventionalist:
      (1) the exact location and anatomic configuration of the lesion, (2) the
      vascularity of a lesion and identification of all feeding and draining vessels,
      and (3) depiction of the regional vascular anatomy of the spinal cord in relation
      to the lesion. Considering the relatively longer length of the procedure, larger
      contrast volumes, and increased complexity (as measured by catheter exchanges
      required) of spinal angiography, however, certain angiographic techniques (e.g.,
      digital subtraction angiography, the use of general anesthesia, or placement of a
      groin sheath to facilitate catheter exchanges) and the use of low osmolality
      contrast agents should be considered to improve the quality of the examination
      while reducing risk.

PMID- 8873095
TI  - Angiography in the evaluation of head and neck trauma.
AB  - Cerebrovascular trauma is a heterogeneous group of injuries including arterial
      dissections, traumatic aneurysms, arteriovenous fistulas, and venous occlusions.
      Detection of vascular trauma may be difficult because of variations in clinical
      presentation; however, in recent years, increased awareness and understanding of
      these injuries has improved the ability to detect and subsequently treat many
      lesions. Despite advances in other imaging modalities, angiography remains the
      primary radiographic tool used in the evaluation of traumatic vascular lesions.

PMID- 8873096
TI  - The role of angiography in the evaluation of vascular and neoplastic disease in
      the external carotid artery circulation.
AB  - Angiography has a defined role in the management of vascular or neurologic
      diseases with less emphasis on screening and diagnosis and greater emphasis on
      pretherapeutic evaluation and endovascular treatment. This is especially true in
      diseases in the external carotid circulation. Advances in catheter technology and
      super-selectivity have improved our understanding of the anatomy and hemodynamics
      in normal and pathologic states. The functional neurovascular anatomy of the
      external carotid artery and diseases in which angiography has a role are
      reviewed.

PMID- 8873097
TI  - The role of angiography in the assessment of atherosclerotic disease. Assessment
      of the carotid bifurcation.
AB  - Paralleling recent developments in noninvasive vascular imaging of the carotid
      bifurcation, there have been several randomized therapeutic trials for carotid
      stenosis to identify which patients should receive treatment. Studies involved in
      neuroimaging have sought ways to evaluate carotid artery stenosis without
      standard angiography, whereas those involved in therapeutic decisions for
      patients with carotid stenosis have attempted to verify the use of carotid
      endartectomy and determine which patients benefit most from treatment. The
      methods of measurement for carotid stenosis, duplex ultrasound measurement
      comparisons, magnetic resonance angiography and computed tomographic angiography,
      and standard radiographic angiography are discussed.

PMID- 8873098
TI  - Angiography of non-atherosclerotic occlusive cerebrovascular disease.
AB  - The growth of noninvasive imaging has limited the indications for angiographic
      evaluation in many types of disease involving the CNS. Nevertheless, angiography
      remains an essential tool for neuroradiologic diagnosis of occlusive
      cerebrovascular disease. Angiography most faithfully depicts cerebrovascular
      anatomy and frequently permits diagnosis of disorders that are incompletely
      evaluated by imaging modalities. In addition, the expanding role of
      interventional neuroradiologic therapy promises to make the role of angiography
      one of increasing prominence and importance in the future.

PMID- 8873099
TI  - The role of angiography in the evaluation of cerebral vascular malformations.
AB  - Although magnetic resonance imaging has become the modality of choice for the
      diagnostic evaluation of cerebral vascular malformations, cerebral angiography
      remains indispensable for the evaluation of cerebral arteriovenous malformations.
      Super-selective angiography allows detailed endovascular exploration of the
      various vascular elements composing cerebral arteriovenous malformations and is
      essential in elucidating their angioarchitecture and for treatment planning.
      Clinicoangioarchitectural correlations further our understanding of the natural
      history of cerebral arteriovenous malformations.

PMID- 8873100
TI  - Angiography of cerebral aneurysms.
AB  - Magnetic resonance and computed tomographic angiography have been increasingly
      applied to the study of disease affecting the cerebral vasculature. Despite these
      advances, however, conventional cerebral angiography clearly remains the
      diagnostic gold standard and essential guide to any microneurosurgical or
      endovascular therapeutic decision concerning cerebral aneurysms. Detailed
      cerebral angiography is a dynamic study and is influenced by prior axial imaging.
      It should be tailored to the specific circumstance to obtain information required
      for selection of the most beneficial treatment.

PMID- 8873101
TI  - Angiographic findings associated with intra-axial intracranial tumors.
AB  - Although computed tomography and, more recently, magnetic resonance imaging, have
      supplanted pneumoencephalography and angiography in the initial evaluation of
      patients with suspected intracranial neoplasms, angiography may still have an
      important role in the diagnosis and management of such individuals. It can define
      normal arterial and venous anatomy (important information in planning surgical
      approaches to some lesions), show vascular abnormalities associated with
      intracranial tumors, evaluate the integrity of the collateral circulation,
      incorporate functional testing for eloquent brain in the vicinity of a lesion,
      and be used in conjunction with the administration of intra-arterial
      chemotherapy.

PMID- 8873102
TI  - Complications of diagnostic cerebral angiography and tips on avoidance.

PMID- 8873103
TI  - The role of computed tomographic angiography in the assessment of intracranial
      vascular disease.
AB  - Both technical and clinical implications of three-dimensional computed
      tomographic angiography in the evaluation of intracranial circulation, and in
      particular cerebral aneurysms, are presented. Three-dimensional computed
      tomographic angiography allows excellent visualization of the aneurysm, its neck,
      and its relationship with the parent artery and important adjacent bony
      structures. This technique has a major role in the evaluation of difficult
      aneurysms. In addition, advantages and disadvantages are discussed in comparison
      with more conventional techniques such as magnetic resonance imaging, magnetic
      resonance angiography, and digital subtraction angiography. Three-dimensional
      computed tomographic angiography will continue to develop with the advent of more
      rapid computed tomography scanners, playing a key role in the investigation and
      screening of patients with a family history of cerebral aneurysms.

PMID- 8873104
TI  - The role of magnetic resonance angiography in the assessment of intracranial
      vascular disease.
AB  - Magnetic resonance techniques have a significant role in the evaluation of
      intracranial vascular diseases; however, to achieve an appropriate diagnosis, a
      combination of both magnetic resonance imaging and angiography are needed. It is
      extremely important for the interpreting physician to be aware of the potential
      limitations of the techniques being used. With this knowledge, magnetic resonance
      techniques can eliminate the need for more invasive procedures. An overview of
      the current methods and their applications and limitations is provided.

PMID- 8873105
TI  - Preclinical neurochemical and electrophysiological profile of 1192U90, a
      potential antipsychotic.
AB  - 11192U90 was submitted to receptor binding and monoamine uptake assays. It bound
      potently at serotonin 5-HT2, dopaminergic D2, serotonin 5-HT1A, and adrenergic
      alpha 1 and alpha 2 receptors. It also bound to dopaminergic D1, serotonin 5-HT3,
      serotonin 5-HT4, and sigma sites, albeit with lower affinity. It was essentially
      inactive at 22 other sites, including those for cholinergic M1 and M2. It weakly
      inhibited uptake of 3H-norepinephrine, 3H-serotonin and 3H-dopamine. Acute doses
      of 1192U90 (5 and 20 mg/kg P.O.) increased whole-brain levels of dopamine
      metabolites but did not affect levels of norepinephrine, dopamine, and serotonin.
      Subcutaneous injection of 1192U90 (0.8 mg/kg/day) and clozapine (20 mg/kg/day)
      for 28 days preferentially decreased the number of spontaneously active dopamine
      cells in the ventral tegmental area (VTA) but not the substantia nigra (SN) of
      rats, as measured by population sampling. This outcome is characteristics of
      atypical antipsychotics like clozapine. Acute injections of 1192U90 reversed the
      rate-inhibiting effects of microiontophoretically applied dopamine and
      intravenously injected apomorphine and d-amphetamine on dopamine cell firing.
      Intravenous injection or iontophoretic application of 1192U90 or the 5-HT1A
      agonist (+/-)8-OH-DPAT inhibited the firing rates of dorsal raphe nucleus (DRN)
      neurons in rats, and the effects of both compounds were blocked by
      iontophoretically applied S(-) propranolol, a 5-HT1A antagonist. The results
      suggest that 1192U90 is a preferential dopamine D2 antagonist as well as a 5-HT1A
      agonist that may prove to be an atypical antipsychotic.

PMID- 8873106
TI  - 1192U90 in animal tests that predict antipsychotic efficacy, anxiolysis, and
      extrapyramidal side effects.
AB  - 1192U90 was developed on the assumption that antagonism of 5-HT2 receptors
      efficacy yields more potently than D2 receptors against positive and negative
      symptoms of schizophrenia with minimal liability for extrapyramidal side effects
      (EPSs), and that 5-HT1A agonism further reduces EPSs and provides anxiolytic and
      antidepressant activity. 1192U90 was submitted to four tests that predict
      antipsychotic efficacy (antagonism of apomorphine-induced climbing in mouse,
      antagonism of apomorphine-induced circling in rats with unilateral 6-OHDA
      lesions, antagonism of amphetamine-induced hyperlocomotion in rat, and inhibition
      of conditioned avoidance in rat), two tests of 5-HT2 function (antagonism of 5
      MeODMT-induced head twitches in mouse and antagonism of 5-HTP-induced wet dog
      shakes in rat), and three tests that predict EPS liability (antagonism of
      apomorphine-induced stereotypy in mouse and rat and induction of catalepsy in
      mouse). ED50s (mg/kg PO) were as follows: climbing 10.1, circling 7.9,
      hyperlocomotion 6.6, and avoidance 5.7; head twitches 5 and wet dog shakes 4.6;
      stereotypy in mouse 91.1, stereotypy in rat 133.4, and catalepsy 192.4. The ratio
      of ED50 for stereotypy antagonism to ED50 for climbing antagonism was 9 (compared
      to 4, 3, and 4 for clozapine, risperidone, and haloperidol). The ratio of ED50
      for catalepsy induction to ED50 for climbing antagonism was 19 (compared to 7, 2,
      and 17 for clozapine, risperidone, and haloperidol). 1192U90 was also submitted
      to three tests that predict anxiolysis: It produced only a small increase in
      punished lever pressing for food in rat (Geller-Seifter conflict test), which is
      specific for rapid-onset efficacy, but produced large increases in punished key
      pecking for food in pigeon and cork gnawing in rat, which identify the delayed
      onset 5-HT1A agonists such as buspirone. The results suggest that 1192U90 would
      be effective for positive and negative symptoms of schizophrenia, with minimal
      liability for EPSs, and may also have anxiolytic properties.

PMID- 8873107
TI  - Lower serum L-tryptophan availability in depression as a marker of a more
      generalized disorder in protein metabolism.
AB  - Recently, it has been reported that major and melancholic depression are
      accompanied by a lower availability of total L-tryptophan (L-TRP) to the brain
      and by significant changes in electrophoretically separated protein fractions,
      such as albumin and alpha 2-globulin. The aim of this study was to examine the
      relationships between serum L-TRP availability and total serum protein, albumin,
      and alpha 2-globulin in 42 depressed and 24 normal subjects. In depressed and
      normal subjects, alone and together, there were significant and positive
      correlations between serum L-TRP and total serum protein or albumin
      concentrations. In the depressed subjects, but not in normal controls, there were
      significant inverse relationships between the L-TRP/competing amino acid ratio
      and the alpha 2-globulin fraction. Serum L-TRP and albumin were significantly
      lower in melancholic subjects than in normal and minor depressed subjects.
      Depressed subjects had a significantly lower L-TRP/competing amino acid ratio and
      significantly higher serum alpha 2-globulin than normal controls. Total serum
      protein was significantly lower in major depressed subjects than in normal
      controls. The results suggest that lower L-TRP availability to the brain in
      depression is related to lower serum albumin and to increased alpha 2-globulin
      fraction, which are both hallmarks of the acute phase response in depression. the
      results further corroborate the hypothesis that lowered L-TRP availability in
      depression is related to the acute phase response in that illness.

PMID- 8873108
TI  - Effects of oral morphine on cold pressor tolerance time and neuropsychological
      performance.
AB  - We investigated the analgesic effects of escalating doses (0.214, 0.286, 0.357,
      and 0.429 mg/kg) of oral morphine on tolerance to painful cold pressor in a
      double-blind, active placebo-controlled (diphenhydramine) study in 45 normal
      volunteers. The highest dose of morphine administered is equivalent to the
      starting dose recommended by the Agency for Health Care Policy and Research for
      the management of cancer pain and acute postoperative pain. We assessed analgesia
      in terms of cold pressor tolerance time and self-reported ratings of pain
      intensity and unpleasantness. Subjects receiving the highest dose of oral
      morphine showed significantly higher tolerance time than subjects receiving
      diphenhydramine. Neither morphine or diphenhydramine significantly reduced
      ratings of pain intensity and unpleasantness. Neuropsychological testing revealed
      that the two highest doses of morphine impaired the episodic retrieval of a word
      list, but the same doses did not affect motor, perceptual, or attentional tasks.

PMID- 8873109
TI  - Effect of stimulus intensity on prolactin and cortisol release induced by
      unilateral electroconvulsive therapy.
AB  - Prolactin (PRL) plasma levels rise several fold in response to electroconvulsive
      therapy (ECT). There is evidence that the magnitude of ECT-induced PRL release
      varies as a function of electrode placement with bilateral (BL) ECT, producing a
      larger PRL increase than does unilateral (UL) ECT. Although there is some
      evidence that the amount of PRL released by ECT may also vary as a function of
      stimulus intensity, the effect of stimulus intensity on the amount of PRL
      released by UL ECT has not been studied. This is an important question because it
      is with UL electrode placement that large differences in clinical efficacy as a
      function of stimulus intensity have been documented. We studied patients
      undergoing a course of UL ECT as the clinically indicated treatment for their
      illness. Subjects received low-dose (threshold) and high-dose (three times the
      threshold) ECT on two consecutive treatments. The order of low- and high-dose
      treatments was counterbalanced. Blood samples were drawn at 15-minute intervals
      before and for 1 hour after the administration of ECT and assayed for PRL and
      cortisol levels. Our results clearly indicate that the PRL and cortisol response
      to UL ECT-induced PRL release varies as a function of stimulus intensity. In
      fact, the amount of PRL released by high-dose UL ECT was nearly three times
      greater than that released by threshold stimulation. These results are consistent
      with the hypothesis advocating that the therapeutic advantage of high-intensity
      over low-intensity UL ECT is the result of greater seizure generalization and
      spread to subcortical regions and suggest that ECT-induced PRL release has the
      potential to distinguish a seizure induced by a therapeutic stimulus from a
      seizure induced by a stimulus known to have little therapeutic effect.

PMID- 8873110
TI  - Effects of valproic acid on beta-adrenergic receptors, G-proteins, and adenylyl
      cyclase in rat C6 glioma cells.
AB  - Valproic acid (VPA) is an anticonvulsant drug with demonstrated efficacy in the
      treatment of mania. In the present study, we found that chronic exposure of rat
      C6 glioma cells to VPA induces a coordinate decrease in multiple components of
      the beta-adrenergic receptor- (beta-AR) coupled cyclic adenosine 3'
      5'monophosphate (cAMP) generating system. Chronic VPA decreased the number of
      beta-ARs in a time- and concentration-dependent manner; the decrease of beta-ARs
      was largely beta 1-AR selective and affected beta-ARs in both the high- and low
      affinity states. Chronic VPA also significantly attenuated receptor- and
      postreceptor-stimulated cAMP production, [3H]forskolin binding sites,
      immunolabeling of G alpha s 45, and cholera toxin catalyzed ADP-ribosylation of G
      alpha s 52 and 45. Although the precise underlying mechanisms remain to be
      elucidated, such profound long-term changes in the functioning of this key
      signaling pathway may help explain the antimanic effects of chronic VPA treatment
      and are worthy of further study.

PMID- 8873111
TI  - Lack of effect of chronic antidepressant treatment on Gs and Gi alpha-subunit
      protein and mRNA levels in the rat cerebral cortex.
AB  - Experimental evidence indicates that chronic antidepressant treatment in rats
      modifies the central nervous system beta-adrenoceptor signaling pathway at
      multiple sites including receptor, G-protein, adenylyl cyclase, and protein
      kinase A. In the present study, we examined the postreceptor effect of
      antidepressant treatment on the protein and mRNA levels of stimulatory and
      inhibitory C protein alpha-subunits (G alpha s and G alpha i) and beta-subunits
      in rats infused continuously with various antidepressants for 21 days. Chronic
      treatment with tricylic (desipramine and amitriptyline) and monoamine oxidase
      inhibiting (tranylcypromine) antidepressants did not significantly affect the
      immunoreactivity levels of G alpha s (both 45- and 52-kDa species), G alpha i1, G
      alpha i2, G beta 36, and beta 35 in rat cerebral cortex. Similarly, the levels of
      mRNA encoding these G protein subunits remained unchanged subsequent to these
      drug treatments. In contrast, cortical beta-adrenoceptor number was significantly
      decreased by these treatments. These results suggest that the adaptive changes of
      rat cerebral cortical beta-adrenoceptor-adenylyl cyclase system often seen after
      chronic antidepressant treatment are not accompanied by changes in the abundance
      and gene expression of G alpha s, G alpha i, or G beta proteins.

PMID- 8873112
TI  - Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and
      diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence.
AB  - The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing
      hormone (CRH) elicit anxietylike symptoms when administered
      intracerebroventricularly to laboratory animals. Because of the similarities
      between the symptoms of certain anxiety states and the alcohol withdrawal
      syndrome, we hypothesized that increased secretion of either of these endogenous
      neuropeptides may, at least in part, be responsible for the symptoms of alcohol
      withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal
      fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and
      again at 3 week's abstinence (Day 21). In addition, plasma concentrations of
      cortisol were measured to evaluate the relationship between pituitary-adrenal
      axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI,
      was significantly higher on Day 1 than on Day 21. Although there was a
      significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a
      significant correlation between CSF CRH and plasma cortisol concentrations was
      not observed at either time point. Neither CSF neuropeptide correlated with
      clinical measures of withdrawal severity. These tentative findings may implicate
      CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the
      central release of CRH and DBI may not be adequately reflected in lumbar CSF.

PMID- 8873113
TI  - Differential inhibition of neuronal and extraneuronal monoamine oxidase.
AB  - This study examined whether the neuronal and extraneuronal sites of action of two
      monoamine oxidase (MAO) inhibitors, l-deprenyl and debrisoquin, could be
      distinguished by their effects on plasma concentrations of catecholamine
      metabolites. Plasma concentrations of the intraneuronal deaminated metabolite of
      norepinephrine, dihydroxyphenylglycol (DHPG), were decreased by 77% after
      debrisoquin and by 64% after l-deprenyl administration. Plasma concentrations of
      the extraneuronal O-methylated metabolite of norepinephrine, normetanephrine,
      were increased substantially more during treatment with l-deprenyl than with
      debrisoquin (255% compared to a 27% increase). The comparable decreases in plasma
      concentrations of DHPG indicate a similar inhibition of intraneuronal MAO by both
      drugs. Much larger increases in normetanephrine after l-deprenyl than after
      debrisoquin are consistent with a site of action of the latter drug directed at
      the neuronal rather than the extraneuronal compartment. Thus, differential
      changes in deaminated and O-methylated amine metabolites allows identification of
      neuronal and extraneuronal sites of action of MAO inhibitors.

PMID- 8873114
TI  - Effects of zolpidem on local cerebral glucose metabolism during non-REM sleep in
      normal volunteers: a positron emission tomography study.
AB  - Using positron emission tomography with fluorodeoxyglucose (18FDG or FDG), we
      compared the effects of zolpidem (10 mg), an imidazopyridine hypnotic, which is
      relatively selective for the BZ1 or omega receptor and placebo on cerebral
      glucose metabolism during the first non-REM sleep period of 12 young normal
      volunteers. Plasma zolpidem pharmacokinetics varied considerably among subjects,
      and plasma concentrations were lower than usually reported. In general, the
      effects of zolpidem on local cerebral glucose metabolism varied directly with
      plasma concentrations of zolpidem. Zolpidem induced changes in local cerebral
      glucose metabolism were unevenly distributed throughout the brain and were
      greater in subcortical areas than lateral cortical areas. Significant negative
      correlations were found between change in local absolute glucose metabolic rate
      (calculated by subtracting individual data on placebo nights from that on
      zolpidem nights) and plasma concentration of zolpidem for the following areas:
      medial frontal cortex, cingulate gyrus, putamen, thalamus, and hippocampus. The
      effects of zolpidem on local cerebral glucose metabolism were partially but not
      closely related to the reported density of BZ1 receptors.

PMID- 8873115
TI  - Natural and cellular immune responses in Flinders sensitive and resistant line
      rats.
AB  - Major depression is associated with impairments in natural and cellular immune
      responses. This study characterized baseline natural and cellular immune function
      in the Flinders Sensitive Line (FSL) genetic animal model of depression and in
      Flinders Resistant Line (FRL) controls. Splenic natural cytotoxicity per natural
      killer (NK) cell was significantly lower in the FSL rats, suggesting that NK
      cells are less activated at rest in the FSL rats than in the FRL controls.
      Neither lymphocyte proliferative responses nor interleukin-2 production differed
      between the two strains. Resting baseline concentrations of plasma
      adrenocorticotropic hormone and corticosterone were similar between the FSL and
      FRL rats, indicating that hypothalamo-pituitary adrenal axis activation did not
      mediate immunological differences. FSL rats show abnormalities in natural
      immunity similar to those found in clinically depressed human beings, indicating
      that this animal model may be useful in understanding the neural and
      neuroendocrine mechanisms associated with immune alterations in depression.

PMID- 8873116
TI  - Intact 5-HT2A receptor exons and the adjoining intron regions in schizophrenia.

PMID- 8873117
TI  - Segmental demyelination induced by cerebrospinal fluid of progressive spastic
      paraparesis: correlation with altered proteolytic parameters.
AB  - Progressive spastic paraparesis (PSP) is a demyelinating disease of the central
      nervous system. We studied the ability of the cerebrospinal fluid (CSF) of
      patients to induce alterations in rat peroneal nerves, and to modify the
      proteolytic activity of trypsin in vitro. Subperineurial injection of native or
      heated CSF of patients induced segmental demyelination and other cytological
      alterations 5-7 days later, in the infiltrated zone, while proximal and distal
      regions were normal. The CSF of normal subjects did not induce demyelination, but
      upon heating, it did so. Trypsin was strongly inhibited by the normal CSF but
      upon heating, its inhibitory activity was replaced by a strong potentiation. In
      contrast, native and heated CSF of patients potentiated trypsin. Our findings
      indicate that (1) the normal CSF contains a thermostable factor that potentiates
      trypsin whose function is overruled by thermolabile protease inhibitors; (2) the
      CSF of PSP patients has a reduced inhibitory activity and a conserved ability to
      potentiate trypsin; and (3) the CSF is endowed with a pathogenic power that
      correlates with an unchecked potentiating activity. We propose that the imbalance
      of a protease system may play a role in the pathogenesis of PSP lesions.

PMID- 8873118
TI  - The role of the basolateral nucleus of the amygdala in the pathway between the
      amygdala and the midbrain periaqueductal gray in the rat.
AB  - We electrophysiologically examined the connection between the basolateral nucleus
      of the amygdala (BLA) and the periaqueductal gray (PAG) and examined the role of
      the central nucleus of the amygdala (CNA) in this pathway. Train electrical
      stimulation of the BLA excited 21% (7/33) and inhibited 27% (9/33) of the cells
      recorded in the PAG. Chemical stimulation of the BLA excited 23% (13/56) and
      inhibited 16% (9/56) of the cells recorded in the PAG. Injection of lidocaine
      into the CNA by itself had no effect on PAG cells (n = 9) or on blood pressure
      but blocked the effect of BLA stimulation on PAG neurons in 78% of the cells
      recorded. It was concluded that: (1) PAG cells respond to BLA stimulation; (2)
      the majority of these cells are located in the dorsolateral and lateral columns
      of the PAG; and (3) the CNA modulates a majority of the activities of the BLA in
      the PAG.

PMID- 8873119
TI  - Role in fast inactivation of conserved amino acids in the IV/S4-S5 loop of the
      human muscle Na+ channel.
AB  - Since it has been shown that point mutations in the S4-S5 loop of the Shaker K+
      channel may disrupt fast inactivation, we investigated the role of three
      conserved amino acids in IV/S4-S5 of the adult human muscle Na+ channel (L1471,
      S1478, L1482). In contrast to the K+ channel mutations, the analogous
      substitutions in the Na+ channel (S1478A/C, L1482A) did not substantially affect
      fast inactivation. Nevertheless, the mutations S1478A/C/Q shifted the voltage
      dependence of steady-state inactivation; L1471Q and S1478C slowed recovery from
      inactivation. In contrast, a novel non-conserved IV/S4-S5 mutation causing
      paramyotonia congenita (F1473S) slowed fast inactivation 2-fold and accelerated
      recovery from inactivation 5-fold. The results indicate involvement of the IV/ S4
      S5 loop of the human muscle Na+ channel in fast inactivation, but different roles
      for conserved amino acids among Na+ and K+ channels.

PMID- 8873120
TI  - H7, an inhibitor of protein kinase C, prevents serum-induced phosphorylation of
      Raf and MAP kinase in neuroblastoma cells.
AB  - We have previously shown that 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine
      (H7), an inhibitor of protein kinase C, inhibits proliferation of neuroblastoma
      cells in culture. We have now tested whether the effect of H7 is mediated by MAP
      kinase and Raf. It is shown that, in Neuro 2a cells, activation of protein kinase
      C by addition of 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA), leads
      to phosphorylation of Raf and Mitogen-activated protein kinase (MAP kinase). PMA
      induced phosphorylation of these proteins is prevented by H7. When quiescent
      Neuro 2a were stimulated to proliferate by addition of serum, Raf and MAP kinase
      were rapidly phosphorylated. Serum-induced phosphorylation of Raf and MAP kinase
      is prevented by H7. These results suggest that, in Neuro 2a cells, the control of
      proliferation by protein kinase C could be mediated by phosphorylation (and
      concomitant activation) of Raf and MAP kinase.

PMID- 8873121
TI  - Effects of glutamate receptor agonists on presumed presynaptic Ca(2+)-signals in
      juvenile rat hippocampal area CA1.
AB  - The physiological role of presynaptic glutamate receptors in controlling
      presynaptic Ca(2+)-influx and thereby transmitter release is unknown. To test if
      presynaptic Ca(2+)-uptake in the hippocampus is controlled by glutamate
      autoreceptors, we created a hippocampal slice preparation for investigation of
      presumed presynaptic Ca(2+)-signals with ion-sensitive microelectrodes after
      lesioning of post-synaptic neurons by glucose deprivation. After prolonged
      glucose deprivation in slices from juvenile animals of postnatal days 13-15 and
      20-22, stratum radiatum (SR) and alveus stimulation-induced postsynaptic field
      potential (fp) components were irreversibly abolished in area CA1, whereas SR
      stimulation still evoked afferent volleys. Repetitive stimulation of the SR still
      induced small decreases in the extracellular Ca2+ concentration ([Ca2+]o), but
      repetitive alveus stimulation no longer induced decreases in [Ca2+]o, suggesting
      a complete damage of pyramidal cells. In lesioned slices the remaining SR
      stimulation-induced small decreases in [Ca2+]o presumably reflect presynaptic
      Ca(2+)-influx. These small decreases in [Ca2+]o were reversibly reduced by
      kainate, RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N
      methyl-D-aspartate (NMDA) and L-glutamic acid (glutamate), without effects on
      afferent volleys.

PMID- 8873122
TI  - Intraseptal injections of NGF attenuates edema formation following septal lesions
      in the rat.
AB  - Rats with electrolytic lesions of the medial septum received a single intraseptal
      injection of either nerve growth factor (NGF) or saline immediately following
      surgery. The formation of edema was then assessed at five time points following
      the lesions to the septum: 6 h, 1 day, 2 days, 3 days, and 5 days. Edema
      formation was detected as early as 6 h in both groups. However, by 2 days
      following surgery, the NGF treated rats had significantly less edema formation
      than their lesion alone counterparts. These results can be taken to indicate that
      NGF may alter locally mediating events that limit the effects of reactions
      associated with the inflammation of damaged tissue.

PMID- 8873123
TI  - Regulation of progesterone receptor gene expression by sex steroid hormones in
      the hypothalamus and the cerebral cortex of the rabbit.
AB  - The effects of estradiol benzoate (EB) and progesterone (P4) upon progesterone
      receptor (PR) gene expression in the cerebral cortex and the hypothalamus of the
      rabbit were studied. Ovariectomized adult rabbits were subcutaneously treated
      with EB (25 micrograms/kg) for 2 days, and with EB (25 micrograms/kg) + a single
      dose of P4 (5 mg/kg) on day 3. Twenty-four hours after the last dose, the frontal
      cortex, the hypothalamus and the uterus were excised, total RNA was extracted and
      processed for reverse transcription-polymerase chain reaction. PR gene expression
      was induced by EB and down-regulated by P4 both in the frontal cortex and the
      hypothalamus in a manner similar to that observed in the uterus. The finding that
      PR gene transcription is regulated by steroid hormones in the cerebral cortex
      suggests that post-transcriptional processes are involved in the insensitivity of
      cortical PR protein to steroids regulation previously reported with binding
      techniques.

PMID- 8873124
TI  - Calbindin D28k-like immunoreactivity in the gustatory epithelium in the rat.
AB  - The distribution of calbindin D28k (CB)-like immunoreactivity (-LI) in the
      gustatory epithelium was examined in the adult rat. In the circumvallate and
      foliate papillae, CB-like immunoreactive (-IR) nerve fibers were observed in the
      subgemmal region, and some of these penetrated the taste buds. Two or three
      spindle-shaped gustatory cells displayed CB-LI in each taste bud of these lingual
      papillae; the immunoreactivity was restricted to the cytoplasm. In the fungiform
      papilla, CB-IR nerve fibers were detected in the subgemmal region, but no CB-IR
      cells were observed in the taste buds of the fungiform papillae. In the taste
      buds of the incisive papillae, many CB-IR intragemmal nerve fibers were observed,
      but no apparent CB-IR cells were detected. In the soft palate, CB-IR nerve fibers
      associated with the taste buds were also observed, but no CB-IR cells were
      detected in the taste buds. The present findings indicate that CB-IR gustatory
      cells were only localized in the taste buds in the posterior lingual papillae
      (circumvallate and foliate papillae), but not in the taste buds in other
      gustatory epithelium.

PMID- 8873125
TI  - Purkinje cell loss and astrocytosis in the cerebellum in familial and sporadic
      Alzheimer's disease.
AB  - In order to elucidate further the pathological differences between familial
      Alzheimer's disease (FAD) and sporadic Alzheimer's disease (SAD), Purkinje cells
      and astrocytosis in the cerebellum of 10 FAD patients including two cases with
      the beta-amyloid precursor protein (APP) gene mutation in codon 717 (APP717 Val-
      >Ile), 10 SAD patients and 10 non-demented, age-matched controls were
      morphometrically investigated using immunohistochemistry. The regions examined
      included the molecular, Purkinje cell and granular cell layers, and the
      cerebellar white matter. This is the first report of a significantly decreased
      Purkinje cell density in FAD when compared to SAD. The density in SAD was also
      significantly decreased when compared to controls. In addition, the astrocyte
      density in FAD was significantly greater than that of SAD in the Purkinje cell
      layer, granular cell layer, and white matter. The density in SAD was also greater
      than that in controls, but not significantly in the granular cell layer and white
      matter. In the cases with the APP717 (Val-->Ile) mutation, Purkinje cell loss in
      the cerebellum was greater than the mean for FAD and SAD cases, while the
      astrocyte density was lower than the mean of all FAD cases, but higher than the
      mean of SAD cases. This study demonstrates that Purkinje cell loss and
      astrocytosis in FAD in the cerebellum are greater than in SAD, indicating that
      the cerebellum is more affected in FAD than in SAD.

PMID- 8873126
TI  - Age-related change of neuropeptide Y-immunoreactive neurons in the cerebral
      cortex of aged rats.
AB  - Recent studies have explored certain changes with aging of neurons containing
      neuropeptides. The extent of loss in aged central nervous system (CNS) of
      neuronal cells containing neuropeptide Y (NPY) has not yet been established with
      certainty, and available data is often contradictory. Changes of NPY-containing
      neurons with aging in the cerebral cortex of aged rat were demonstrated by
      immunocytochemistry. A major loss of NPY-immunoreactive (ir) neurons in the aged
      rat brain was observed in the retrosplenial cortex, frontal cortex area 1 and 2,
      parietal cortex area 1 and 2, occipital cortex area 1 and 2, temporal cortex area
      3, cingulate cortex and the hippocampus proper. A loss of NPY-ir neurons was
      observed mostly in layers V and VI; in addition, the number and length of
      dendritic branches appeared to be decreased and shortened in the age group. These
      results indicate the involvement of NPY-ir neurons in the aging process of
      cerebral cortex, and provide the first morphological evidence for the loss of NPY
      neurons in the cerebral cortex of aged rats.

PMID- 8873127
TI  - Transcranial Doppler assessment of cerebral blood flow velocity during visual
      spatial selective attention in humans.
AB  - Blood flow velocities of the posterior cerebral arteries were obtained while
      healthy subjects were engaged in a visual spatial attention task. Experimental
      runs consisted of series of stimuli comprised of four elements (two left and two
      right of a central fixation point) presented briefly in blue against a purple
      screen. After a period of passive viewing a left or right pointing arrow
      indicated the visual half-field to be attended by the subjects in order to detect
      identical symbols on the attended side. Relative to the passive viewing condition
      a marked increase of flow was seen in both posterior cerebral arteries during the
      attention period. No differential increase of flow as a function of attended
      field was detected. These results are discussed in comparison with recent
      positron-emission tomography (PET) and electrophysiological data obtained with
      the same task.

PMID- 8873128
TI  - Evidence that glucose metabolism is decreased in the cerebrum of aged female
      senescence-accelerated mouse; possible involvement of a low hexokinase activity.
AB  - d-Glucose metabolism in cerebral cells prepared from aged senescence-accelerated
      mouse (SAM), was investigated in consideration of a sex difference. The
      production of 14CO2 from 6-[14C]D-glucose was reduced in female senescence
      accelerated-prone mouse (SAMP) 8, a prone substrain, in comparison with that in
      female senescence-accelerated-resistant mouse (SAMR) 2, a control substrain,
      whereas there was no difference in males. The 2-deoxy-D-glucose uptake into
      cerebral cells from female SAMP8 was also lower than that of control mice. But,
      the 3-O-methyl-D-glucose uptake in SAMP8 was higher than that of SAMR2,
      suggesting that the low hexokinase activity was involved in the decreased glucose
      metabolism in cerebrum of SAMP8 females irrespective of glucose transporter. This
      possibility was supported by the finding that the contents of glucose 6-phosphate
      produced from glucose added to cerebral cells from SAMP8 was lower than that in
      ICR mice.

PMID- 8873129
TI  - Strong c-Jun immunoreactivity is associated with apoptotic cell death in human
      tumors of the central nervous system.
AB  - Strong c-Jun immunoreactivity, but not c-Fos expression, was observed in typical
      apoptotic cells in medulloblastomas, central neuroblastomas, malignant
      astrocytomas and glioblastomas, and in lymphocyte-like cells bearing nuclear
      fragmented DNA in medulloblastomas. In contrast, only a few proliferating cells,
      as revealed with PCNA immunohistochemistry, colocalized c-Jun. These results
      support the concept that strong c-Jun expression is associated with certain forms
      of cell death in human tumors of the central nervous system.

PMID- 8873130
TI  - Melatonin receptors in the suprachiasmatic nuclei and pars tuberalis of
      testosterone induced photoresponsive rats.
AB  - The sexual axis of rats can be rendered photoresponsive by testosterone implants.
      We have studied in these conditions whether rat pars tuberalis (PT) melatonin
      receptor density would be decreased after exposure to short photoperiod (SP) like
      as observed in long day seasonal breeders. The answer is no, but we observed that
      testosterone induced a photoperiod independent decrease in PT melatonin receptor
      density. These results show that testosterone-induced photosensitivity in rat is
      not linked to an SP-induced decrease in PT melatonin receptor density. However,
      testosterone regulates PT melatonin receptors independently of the photoperiod.

PMID- 8873131
TI  - Anticoagulant factor protein S inhibits the proliferation of rat astrocytes after
      injury.
AB  - The actions of protein S (PS) on the scratch injury-induced proliferation of rat
      astrocytes (AC) were studied. PS (10-300 nM) markedly inhibited [3H]thymidine
      incorporation into injured AC. The effect of 100 nM PS was comparable with that
      of transforming growth factor-beta 1 (TGF-beta 1; 20 ng/ml). The incorporation of
      bromodeoxyuridine, which is usually detectable in AC along the border of the
      wound, was undetectable in the presence of 300 nM PS. The level of PS mRNA in the
      injured AC was slightly increased 15 h after the injury, although the level of
      its receptor, Tyro 3 mRNA was not changed significantly. The results of the
      present study suggest that PS plays an important role in tissue repair processes
      in the central nervous system (CNS) by suppressing the proliferation of AC as in
      the case of TGF-beta 1.

PMID- 8873132
TI  - Decrease in exploratory behavior in naturally occurring cholecystokinin (CCK)-A
      receptor gene knockout rats.
AB  - We recently found a specific strain of rats (Otsuka Long Evans Tokushima Fatty;
      OLETF rats) lacking cholecystokinin (CCK)-A receptor because of a genetic
      abnormality. Since CCK is an abundant neurotransmitter peptide in the brain, we
      examined whether these animals exhibit any behavioral abnormalities by conducting
      open-field tests. OLETF rats showed hypolocomotor activity and a decrease in the
      incidence of rearing in open-field tests. CCK release from the synaptosomes, and
      levels of CCK and CCK-B receptor mRNAs were the same as those observed in normal
      rats. It is suggested that the decreased exploration in OLETF rats may be due to
      the lack of CCK-A receptor.

PMID- 8873134
TI  - Assignment of Alzheimer's presenilin-1 (PS-1) gene to 14q24.3 by fluorescence in
      situ hybridization.
AB  - Presenilin-1 (PS-1) was suggested to be localized on 14q24.3 based on linkage
      analysis and cDNA cloning. The final identification of PS-1 as the causal gene
      for Alzheimer's disease (AD) was concluded based on finding of the point
      mutations in the candidate cDNA linked with pedigrees with early-onset familial
      AD. We present evidence of its physical genome mapping of PS-1 by fluorescence in
      situ hybridization method.

PMID- 8873133
TI  - The synaptic structure of PACAP immunoreactive axons in the intermediolateral
      nucleus of the rat.
AB  - Immuno-electronmicroscopic studies were performed to detect the presence and
      features of synaptic contacts between pituitary adenylate cyclase activating
      polypeptide immunoreactive (PACAP-ir) axons and cholera toxin B-horseradish
      peroxidase labeled preganglionic sympathetic neurons (PSNs) in the
      intermediolateral nucleus of the rat thoracic spinal cord. PACAP-ir axon
      varicosities, which contained small clear and large core synaptic vesicles, were
      found to form asymmetric type of synaptic contacts with dendrites and
      infrequently with somata of labeled preganglionic neurons. The present study
      provides ultrastructural evidence of PACAP-ir synaptic contacts with PSNs,
      raising the possibility that the peptide may function as a transmitter/modulator
      to these neurons.

PMID- 8873135
TI  - Topical acetylsalicylate attenuates capsaicin induced pain, flare and allodynia
      but not thermal hyperalgesia.
AB  - The effect of acetylsalicylic acid (ASA) on capsaicin-evoked activation of
      cutaneous nociceptors was tested in a double blind study in 10 volunteers.
      Capsaicin (2% in ethanol) was applied topically for 30 min. Topical ASA (0.25
      g/ml) reduced pain intensity and axon reflex flare size. Also, areas of secondary
      hyperalgesia to light touch and pin-prick were diminished. In contrast, capsaicin
      induced heat hyperalgesia was unaffected by ASA. It is concluded that ASA
      counteracts the excitatory effects of capsaicin on nociceptors and mechanical
      hyperalgesia but not its sensitizing action to heat.

PMID- 8873136
TI  - Dynamical organisation of the human visual system revealed by lifetimes of
      activation traces.
AB  - Magnetic source imaging reveals a dynamical organisation of visual cortical areas
      suggesting that the participation of local memories is an essential component of
      visual information processing. Response recovery studies provide evidence that
      each responding cortical area supports a memory function with a well-defined
      lifetime. The areas fell into two groups, the earliest in occipital lobes with
      lifetimes ranging from 0.1 to 0.6 s, and the later ones in temporal, parietal,
      and frontal areas with lifetimes ranging from 7 to 30 s. Also, within each group
      the areas responding later tended to have longer lifetimes.

PMID- 8873137
TI  - Regional distribution of heparin-binding epidermal growth factor-like growth
      factor mRNA and protein in adult rat forebrain.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently
      described member of the EGF family that binds to and stimulates phosphorylation
      of the EGF receptor (EGFR). In this study, we examined the cellular localization
      of HB-EGF gene transcripts and protein in adult rat forebrain. In situ
      hybridization studies showed that neurons in various regions, including cortex,
      hippocampus, and deep structures, express HB-EGF mRNA. Positively labeled cells
      were also present in white matter, which suggests that both neurons and glia
      express HB-EGF mRNA. Immunohistochemical studies with an antibody specific to
      proHB-EGF, a transmembrane form of HB-EGF, demonstrated ubiquitous
      immunoreactivity in neurons and glial cells in white matter. In view of the wide
      expression of its cognitive receptor, EGFR, in central nervous system neurons,
      our results suggest that HB-EGF is an endogenous ligand for EGFR in the central
      nervous system and may play an important role in physiological conditions.

PMID- 8873139
TI  - Biochemical evidence of the sodium influx stimulating related peptide in the
      brain of the leech Theromyzon tessulatum.
AB  - This paper reports the immunocytochemical and biochemical evidence of a sodium
      influx stimulating related peptide (SIS-like peptide) in the brain of the leech
      Theromyzon tessulatum. Cells immunoreactive to both polyclonal antisera raised
      against the N-terminal (fragment 10-19) or the C-terminal (fragment 67-76)
      sequences of the purified freshwater snail Lymnaea stagnalis sodium influx
      stimulating peptide (SISP) was detected in the brain of this leech. These
      immunocytochemical data were strengthened by biochemical results at the level of
      the protein and by in vitro translated RNA. By combined techniques i.e. high
      performance gel permeation chromatography, electrophoresis followed by immunoblot
      analysis with the two antisera and immunoprecipitation, we established the
      existence in leeches of a protein of ca 11 kDa and its precursor, a protein of ca
      13 kDa related to the SISP. Moreover, results of injections of anti-SISP (10-19)
      preabsorbed or not with its homologous antigen to Theromyzon tessulatum confirmed
      the SIS-like substance involvement in osmoregulation by an anti-diuretic
      function.

PMID- 8873138
TI  - Muscarinic antagonists microinjected into the subthalamic nucleus decrease
      muscular rigidity in reserpinized rats.
AB  - The ability of anticholinergic agents microinjected into the subthalamic nucleus
      to reduce reserpine-induced muscular rigidity was assessed in rats. The
      electromyographical activity of the gastrocnemius-soleus muscle was used as a
      parameter of muscular rigidity. Reserpine (5 mg/kg i.p.) produced the appearance
      of electromyographical activity. The muscarinic antagonists M3 (1.27 nmol of 4
      DAMP) and M1 (2.36 nmol of pirenzepine) markedly reduced the reserpine-induced
      electromyographical activity, whereas the M2 antagonist AFDX-116 (2.37 nmol) had
      no effect. These results suggest that a high cholinergic tone in the subthalamic
      nucleus is associated with the reserpine-induced muscular rigidity. Moreover, the
      M3 muscarinic antagonist is more effective than the M1 muscarinic antagonist in
      reducing the muscular rigidity in reserpinized rats, a model of Parkinson's
      disease, by blocking the high cholinergic tone in the subthalamic nucleus.

PMID- 8873140
TI  - Na+,K(+)-ATPase activity in the cochlear lateral wall of the gerbil.
AB  - We examined Na+,K(+)-ATPase activity in four regions of the gerbil cochlear
      lateral wall by measuring intracellular Na+ concentration ([Na+]i). The
      application of 1 mM ouabain and removal of external K+ caused a most striking
      increase in [Na+]i of the suprastrial fibrocytes, followed by the stria
      vascularis and the type II fibrocytes, but no detectable response in the type I
      fibrocytes. These results may imply the potency of the Na+,K(+)-ATPase activity.
      The high values of the resting [Na+]i in these cells under perilymph-like
      solution returned to the [Na+]i within physiological values after exposure to low
      Na+ conditions similar to endolymph. Our results are interpreted in the light of
      recent morphological findings with regard to the roles in the secretion of K+
      into endolymph of several cell types within the lateral wall.

PMID- 8873141
TI  - Ibotenic acid in the medial septum increased brain-derived neurotrophic factor
      mRNA levels in the dorsal rat hippocampal formation.
AB  - Excitotoxic lesion of the medial septum with ibotenic acid leading to partial
      disappearance of the septal cholinergic nerve cells was used to investigate the
      role of cholinergic mechanisms in the control of trophic factors for hippocampal
      plasticity, namely brain-derived neurotrophic factor (BDNF) and glucocorticoid
      receptor (GR). Their mRNA levels were tested by in situ hybridization 13 days
      after the lesion. A persistent and widespread increase of BDNF mRNA was found in
      all parts of the dorsal hippocampal formation that was not accompanied by a
      significant modification in GR expression. The present data suggest that
      subcortical excitotoxic lesions at the septal level have long-term consequences
      for the adaptive trophic responses occurring in the dorsal hippocampus.

PMID- 8873143
TI  - Repeated electroconvulsive stimulation impairs synaptic plasticity in the dentate
      gyrus in vivo but has no effect in CA1 in vitro.
AB  - Repeated electroconvulsive stimulation (ECS) spaced at 48 h intervals
      significantly increased the synaptic response in the dentate gyrus in vivo, as
      measured by input/output curves, and reduced the degree of long-term potentiation
      (LTP) obtained following high frequency stimulation. An identical course of ECS
      had no effect on synaptic responses recorded in the stratum radiatum of CA1 in
      vitro and did not impair high frequency-induced LTP. These results suggest that
      either ECS has a selective effect on the sub-fields of the hippocampus or that in
      vitro recording techniques are unsuitable for detecting the increase in synaptic
      efficacy produced by the treatments.

PMID- 8873142
TI  - Neostriatal dopamine depletion and locomotor abnormalities due to the Albino
      Swiss rat agu mutation.
AB  - The sub-strain of Albino Swiss rat (AS/AGU) is a spontaneous mutation
      characterised by an ungainly, staggering gait, hindlimb rigidity, whole body
      tremor and (when symptoms are fully developed) difficulty in initiating movement;
      it exhibits a progressive decrease in dopaminergic cells within the substantia
      nigra. A breeding programme involving Albino Swiss (AS) and AS/AGU parent rats
      was used to produce the F1 offspring of AS x AS/AGU matings and, subsequently, F1
      x AS/AGU back crosses. When adult, the movement of all animals was assessed blind
      by observers on three occasions, each animal being identifiable by a subcutaneous
      transponder implanted before weaning. All AS/AGU and half the F1 x AS/AGU back
      cross animals had abnormal gait, while all AS, F1 and the remaining F1 x AS/AGU
      backcross animals showed normal gait, implying that the mutation is recessive.
      Brains of males aged 12-15 months (n = 10 per group) were sectioned transversely
      on a cryostat (-20 degrees C) to produce a cut face just caudal to the anterior
      commissure (approximately Bregma -0.5 mm) and 1 mm diameter x 1 mm deep
      micropunches were taken from three areas of the caudate-putamen. Levels of
      dopamine were measured in all samples by high performance liquid chromatography
      with electrochemical detection (HPLC-ECD) followed by protein estimation. Levels
      of dopamine in the dorsal and middle caudate-putamen varied according to a simple
      inheritance pattern, being high in males from AS, F1 and F1 x AS/AGU back crosses
      without locomotor impairment, but lower in AS/AGU and F1 x AS/AGU back crosses
      with disordered gait. Dopamine levels in the ventral caudate-putamen did not show
      such a clear variation.

PMID- 8873144
TI  - Widespread ectopic neuropeptide-Y immunoreactivity in contralateral mossy fibres
      after a unilateral intrahippocampal kainic acid injection in the rat.
AB  - Granule cells of the dentate gyrus can express neuropeptide-Y (NPY) in several
      models of epilepsy involving limbic seizures, however, the nature of this ectopic
      expression is not well understood at present. We have studied the expression of
      NPY-immunoreactivity in mossy fibres contralateral to a unilateral
      intrahippocampal injection of kainic acid and report that ectopic mossy fibre NPY
      immunoreactivity is observed throughout the contralateral hippocampus.

PMID- 8873145
TI  - Superactivation of transglutaminase type 2 without change in enzyme level occurs
      during progressive neurodegeneration in the mnd mouse mutant.
AB  - We have investigated the activity of the Ca(2+)-dependent apoptosis-related
      transglutaminase type 2 in the mnd/mnd mouse mutant. Transglutaminase activity in
      mnd/mnd central nervous system (CNS) tissue homogenates was identical to that of
      healthy animals at 3 months of age, but at 8 months it was greater in the mnd/mnd
      CNS by up to four times, depending on the region. Western blot analysis showed no
      difference in the level of immunoreactive transglutaminase type 2 in spinal cord
      homogenates between mnd/mnd and healthy mice. However, a greater number of acyl
      donor protein substrates of transglutaminase were identified in mnd/mnd tissue. N
      epsilon (gamma-Glutamyl)lysine cross-linked product of transglutaminase activity
      was localized to the soma of degenerating motor neurons in the mnd/mnd mouse
      spinal cord. We conclude that neurodegeneration in the mnd/mnd mouse is
      accompanied by activation of transglutaminase at substrate level. Possible
      mechanisms of activation and its implications for cellular pathology are
      discussed.

PMID- 8873146
TI  - Increased tau immunoreactivity in oligodendrocytes following human stroke and
      head injury.
AB  - Tau immunohistochemistry was performed on post-mortem brain tissue from patients
      who died following head injury or stroke and from neurologically normal controls.
      Tau-positive oligodendrocytes were detected with three different tau antibodies
      in head injured or stroke patients, but not in control cases. Tau-positive
      oligodendrocytes were detected 2 h following head injury indicating that
      accumulation of tau may be an acute response of these cells to brain injury. The
      mechanisms underlying accumulation of tau in oligodendrocytes after acute brain
      injury may be similar to those which occur in chronic neurodegenerative
      conditions such as progressive supranuclear palsy (PSP) and multi-system atrophy
      (MSA).

PMID- 8873147
TI  - Presence of macrophage migration inhibitory factor (MIF) in ependyma, astrocytes
      and neurons in the bovine brain.
AB  - We investigated the immunohistochemical localization of a cytokine macrophage
      migration inhibitory factor (MIF) in the bovine brain. MIF was present in the
      ependymal cell linings of the cerebral ventricles throughout. Double
      immunostaining of the section with anti-glial fibrillary acidic protein (GFAP)
      antibody and with anti-MIF antibody showed that the astrocytes present in
      subependymal layer were immunoreactive for MIF. In the hippocampus, the pyramidal
      cells in the CA3 and CA4 subfields and the granule cells of the dentate gyrus
      were immunoreactive. The bundles of mossy fibers were stained along their
      projections to CA3 and CA4 regions. The nuclei of the subpopulation of these MIF
      immunoreactive cells were also immunostained. These results indicated the
      widespread distribution of a cytokine, MIF, in the bovine brain and suggested the
      possibility that MIF might play additional roles than a proinflammatory mediator
      role in the brain.

PMID- 8873148
TI  - Sympathetic vasoconstrictor neurons projecting from the guinea-pig superior
      cervical ganglion to cutaneous or skeletal muscle vascular beds can be
      distinguished by soma size.
AB  - We have used a combination of retrograde axonal tracing and intracellular dye
      injections to determine the soma size of sympathetic vasoconstrictor neurons
      projecting from the superior cervical ganglion to the cutaneous vascular bed of
      the eartips, or to the vascular beds of the masseter muscle, of guinea-pigs.
      Neurons projecting to vasculature of the masseter muscle had a cross-sectional
      area of 956 +/- 295 microns2 (mean +/- SD; n = 45 cells) and were significantly
      larger than neurons projecting to the vasculature of the eartip skin (mean cross
      sectional area +/- SD, 604 +/- 251 microns2; n = 39 cells). These results are
      consistent with physiological observations showing that muscle vasoconstrictor
      neurons have faster conduction velocities than cutaneous vasoconstrictor neurons.
      Furthermore, they suggest that muscle vasoconstrictor neurons may innervate a
      larger volume of vasculature compared with cutaneous vasoconstrictor neurons.

PMID- 8873149
TI  - An evaluation of neuronal nicotinic acetylcholine receptor activation by
      quaternary nitrogen compounds indicates that choline is selective for the alpha 7
      subtype.
AB  - The agonist properties of acetylcholine (ACh), tetramethylammonium, ethyl
      trimethylammonium and choline were evaluated for muscle and neuronal nicotinic
      receptors in Xenopus oocytes. The only essential feature for a neuronal receptor
      agonist appears to be the charged nitrogen. For specific receptor subtypes, other
      structural elements appear permissive (neither increasing nor decreasing
      activity) or non-permissive (decreasing activity). Choline was a full agonist for
      alpha 7, but a hydroxyl group was strongly non-permissive for other receptor
      subtypes (alpha 1 beta 1 gamma delta, alpha 3 beta 4, alpha 3 beta 2, and alpha 4
      beta 2). The binding of these ligands to brain membranes is consistent with the
      electrophysiological results. Physiological concentrations of choline desensitize
      alpha 7 receptors to ACh suggesting that, in vivo, choline may regulate both the
      activation and inactivation of this receptor.

PMID- 8873150
TI  - Immunofluorescence analysis of antisense oligodeoxynucleotide-mediated 'knock
      down' of the mouse delta opioid receptor in vitro and in vivo.
AB  - We have previously used antisense oligodeoxynucleotides (ODN) to the cloned delta
      opioid receptor (DOR) to inhibit the antinociceptive response to spinally
      administered delta opioid receptor selective agonists in mice. Here we have
      examined the effect of DOR antisense ODN treatment on the level of DOR expressed
      in NG 108-15 cells and the spinal cord, through immuno-fluorescence microscopy,
      to determine the efficiency and selectivity of the antisense ODN-mediated "knock
      down' of the DOR in these tissues. Antisense ODN, but not mismatch control,
      treatment resulted in a significant reduction in DOR immunoreactivity (-ir) in NG
      108-15 cells and spinal cord. Thus, the inhibition of antinociceptive response to
      intrathecal delta selective agonists by DOR antisense ODN correlates with the
      loss of DOR-ir in the superficial layers of the dorsal horn of the spinal cord.

PMID- 8873151
TI  - Reduction of excitotoxicity-induced brain damage by the competitive NMDA
      antagonist CGP 40116: a longitudinal study using diffusion-weighted imaging.
AB  - The cerebroprotective properties of the competitive N-methyl-D-aspartate (NMDA)
      antagonist CGP 40116 were evaluated in a rat model of excitotoxicity-induced
      brain damage using direct intrastriatal injection of quinolinic acid and
      subsequent (5 or 45 min later) i.p. administration of the drug. Diffusion
      weighted magnetic resonance imaging (DWI) was used to follow the temporal lesion
      growth during the acute phase (4 h) and T2-weighted MRI (T2WI) to quantify
      vasogenic edema extent 2 days later. For control animals, we found a rapid
      increase in lesion volume during the first hour followed by a moderate growth
      over the following hours. The DWI-visible hyperintensity was partially reversible
      after treatment with CGP 40116. The onset of action of CGP 40116 was immediate.
      The final outcome (63% reduction of lesion volume within 2-4 h post-surgery) was
      independent of the time of drug administration. DWI data after 4 h correlated
      well with those obtained by T2WI 2 days later. DWI is a valuable method for early
      prediction of the outcome of therapeutic interventions of excitotoxic insults.

PMID- 8873152
TI  - Amyloid beta proteins reduce the GABA-induced Cl- current in identified Aplysia
      neurons.
AB  - The amyloid beta protein (A beta P) is the major component of the amyloid
      deposition which characterizes Alzheimer's disease. Effects of extracellularly
      applied A beta P on the gamma-aminobutyric acid (GABA)-induced Cl- current
      recorded from identified neurons (R9 and R12) of Aplysia kurodai were
      investigated with conventional voltage-clamp and pressure ejection techniques.
      Focal application of 100 nM A beta P (1-40) reduced the GABA-induced
      hyperpolarization at resting membrane potential and the GABA-induced Cl- current
      in the neurons held at -50 mV. Bath-applied 100 nM A beta P fragments (1-40) and
      (25-35) but not A beta P (1-16) inhibited the GABA-induced Cl- current as well as
      muscimol-induced Cl- currents in the neurons without affecting the resting
      membrane conductance or holding current. These results suggest that A beta P may
      increase neuronal excitability by inhibiting GABA-induced Cl- current in the
      neurons of mammalian central nervous system.

PMID- 8873153
TI  - The effect of dark-rearing, strobe-rearing and acute visual cortex removal on the
      visual responses in the superficial superior colliculus of the guinea-pig.
AB  - Extracellular multi-unit responses to visual stimuli were recorded in the cells
      of the superficial layers of the superior colliculus (SC) in four groups of adult
      guinea-pigs: a control group, a strobe-reared group, a dark-reared group and a
      group with the ipsilateral visual cortex removed acutely. Single unit visual
      responses were also recorded in a control and a dark-reared group. When guinea
      pigs were either strobe or dark-reared from birth, the number of directionally
      selective responses in the superficial SC decreased significantly. Acute removal
      of the visual cortex had no affect on the number of directionally selective cells
      recorded in the SC. The correlation between azimuthal visual receptive field and
      rostrocaudal position of the recording electrode in the SC was not significantly
      different from the control group following strobe, dark-rearing or acute visual
      cortex removal. These data imply that, during early development, visual
      information is necessary for directional selectivity of the visual responses in
      the superficial SC. However, the map of visual azimuthal space is essentially
      unperturbed by visual restriction (in the form of dark or strobe-rearing) or
      acute visual cortex removal.

PMID- 8873154
TI  - Gender bias? Or is it really less work to care for women?

PMID- 8873155
TI  - Gaucher's disease in pregnancy.
AB  - Gaucher's disease is an autosomal recessive lysosomal storage disease, resulting
      from a deficiency of the enzyme glucocerebrosidase, important for the physiologic
      recycling of cell membrane lipids. The clinical symptoms and disease
      presentations of Gaucher's disease are heterogeneous, including
      hepatosplenomegaly, bone "crisis" and fracture, anemia, thrombocytopenia and in
      some forms, rapid neurological decompensation. Similarly, the genetic variability
      of Gaucher's disease is diverse, and in some aspects affects phenotypic
      expression. Type 1 Gaucher's disease, however, usually present with less severe
      symptoms, at more advanced age, and is particularly amenable to enzyme
      replacement therapy with alglucerase. In type 1 patients with Gaucher's disease
      reproductive age is commonly reached and childbearing frequently desired with
      need for appropriate prenatal diagnosis, counseling and careful obstetrical
      surveillance. Although pregnancy concurrent with Gaucher's disease has been
      reported in the medical literature, only one small series of alglucerase treated
      Gaucher's disease during pregnancy exists. Without treatment, pregnancy
      concurrent with Gaucher's disease has several risks including an increased
      severity of anemia and thrombocytopenia that can potentiate postpartum bleeding,
      significant increases in organomegaly and possibly an increased spontaneous
      abortion rate. It is yet to be shown whether alglucerase reduces the risk of
      these complications during pregnancy and whether its use has any adverse effect
      on fetal development.

PMID- 8873156
TI  - Early complications of laparoscopic hysterectomy.
AB  - Since Reich first described laparoscopic hysterectomy (LH) in 1989, a number of
      series have appeared in the literature detailing complications of this procedure.
      This review included all series obtained through a MEDLINE search from April 1989
      through October 1994. Also included were series from the Journal of Gynecologic
      Surgery, Gynaecological Endoscopy, and the Journal of the American Association of
      Gynecologic Laparoscopists. Rates of various complications were calculated and
      compared with existing standards for abdominal and vaginal hysterectomy.
      Hemorrhage and injury to adjacent organs were fairly similar between traditional
      hysterectomy methods and LH. Infectious morbidity, however, was decreased in LH.
      Caution should be used in interpreting these data, as these initial reports come
      predominantly from leading experts in the field of endoscopic surgery. Whether
      these rates can be duplicated in a community hospital is debatable.

PMID- 8873157
TI  - Obstructed labor injury complex: obstetric fistula formation and the multifaceted
      morbidity of maternal birth trauma in the developing world.
AB  - Prolonged obstructed labor may produce injuries to multiple organ systems. The
      best known, and most common, of these injuries is obstetric fistula formation.
      When obstructed labor is unrelieved, the presenting fetal part is impacted
      against the soft tissues of the pelvis and a widespread ischemic vascular injury
      develops that results in tissue necrosis and subsequent fistula formation. Unlike
      the postsurgical vesicovaginal fistula, however, which is usually the result of
      focal trauma to otherwise healthy tissues, the obstetric fistula is the result of
      a "field injury" to a broad area. The field injury that is produced by prolonged
      obstructed labor may result in multiple birth-related injuries in addition to (or
      instead of) a vesicovaginal fistula. Focusing simply on the "hole" between the
      bladder and the vagina ignores the multifaceted nature of the injury that many of
      these patients have sustained. These injuries may include total urethral loss,
      stress incontinence, hydroureteronephrosis, renal failure, rectovaginal fistula
      formation, rectal atresia, anal sphincter incompetence, cervical destruction,
      amenorrhea, pelvic inflammatory disease, secondary infertility, vaginal stenosis,
      osteitis pubis, and foot-drop. In addition to their physical injuries, women who
      have experienced prolonged obstructed labor often develop serious social
      problems, including divorce, exclusion from religious activities, separation from
      their families, worsening poverty, malnutrition, and almost unendurable
      suffering. Isolated almost exclusively to the developing world, particularly
      Africa, this problem has not received the international attention that it
      deserves, from either a medical or a social standpoint.

PMID- 8873158
TI  - Results of a prospective randomized trial comparing standard dose neuraxis
      irradiation (3,600 cGy/20) with reduced neuraxis irradiation (2,340 cGy/13) in
      patients with low-stage medulloblastoma. A Combined Children's Cancer Group
      Pediatric Oncology Group Study.
AB  - PURPOSE: To determine in a prospective randomized trial the effect on survival,
      progression-free survival, and patterns of relapse of a decrease in the neuraxis
      radiation dose from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions in
      patients with newly diagnosed medulloblastoma between 3 and 21 years of age with
      low T stage (T1, T2 and T3A), minimal postoperative residual tumor, and no
      evidence of dissemination (M0). METHODS AND MATERIALS: Between June 1986 and
      November 1990, the Children's Cancer Group and the Pediatric Oncology Group
      randomized 126 patients in a two-arm study comparing the two different doses of
      neuraxis irradiation. In both arms, the posterior fossa received 5,400 cGy in 30
      fractions. All patients were staged with myelography, postoperative lumbar
      cerebrospinal fluid cytology, and postoperative contrast-enhanced cranial
      computerized tomography to ensure no evidence of dissemination and no more than
      1.5 cm3 residual tumor volume. Overall survival, progression-free survival, and
      patterns of recurrence were carefully monitored. Prospective endocrine and
      psychometric studies were performed to determine the benefit of decreasing the
      neuraxis radiation dose. RESULTS: Following an interim analysis at a median time
      on study of 16 months, the study was closed, since a statistically significant
      increase was observed in the number of all relapses as well as isolated neuraxis
      relapses in patients randomized to the lower dose of neuraxis radiation.
      CONCLUSIONS: In patients with newly diagnosed medulloblastoma considered to have
      a good prognosis on the basis of low T stage, minimal residual tumor after at
      least subtotal resection, and no evidence of dissemination after thorough
      evaluation, there is an increased risk of early relapse associated with lowering
      the dose of neuraxis radiation from 3,600 cGy in 20 fractions to 2,340 cGy in 13
      fractions.

PMID- 8873159
TI  - Hyperfractionated craniospinal radiation in medulloblastoma.
AB  - From 1986 to 1991, 13 patients at Northwestern Memorial Hospital were entered
      onto a pilot study designed to test the feasibility of treating children with
      medulloblastoma (11 patients) or primitive neuroectodermal tumors of the cerebral
      hemispheres (2 patients) with hyperfractionated craniospinal radiotherapy
      (HFxRT). Follow-up times ranged from 10 to 96 months with a median of 53 months.
      The patients were prospectively divided among three treatment arms depending on
      prior treatment history, if any, and degree of surgical resection. The 3 patients
      in group I had undergone gross total resection of the primary site, receiving
      64.8 Gy to the primary site and 31.2 Gy directed to the craniospinal axis (CSA).
      Of these 3 patients, patient 1 had residual disease in the thoracic spine at T
      10. The 8 patients in group II, who had gross residual disease remaining at the
      primary site, received 72 Gy to the primary site and 34 Gy to the CSA. Five of
      these eight patients in group II also received 8-in-1 chemotherapy. The 2
      patients in group III had already failed chemotherapy and were then treated with
      60 Gy to the primary site and 26 Gy to the CSA. Of the 11 patients in groups I
      and II, 7 of the 11 (64%) have never recurred. Two of the three group-I patients
      have not recurred, and 5 of the 7 group-II patients have not recurred. In
      addition, patient 7 (group II) remains alive after salvage with bone marrow
      transplant, following a local failure bordering the tentorium. Unfortunately,
      neither of the group-III patients could be salvaged with HFxRT. Acute/subacute
      toxicities included 7 cases of external auditory canal or skin desquamation, 2
      cases of postradiation somnolence, and 1 case each of poor wound healing and
      neutropenia. Chronic toxicities included hypothyroidism in 2 patients and growth
      problems in 2 patients. Neuropsychologic complications affected only the 3
      youngest patients in the study. Three patients developed neurologic sequelae
      attributed to radiation, including 1 with progressive urinary incontinence, 1 who
      developed a transient ischemic attack, and 1 who became progressively ataxic. Our
      research, although based on a small number of patients, suggests that
      hyperfractionated radiation therapy to craniospinal access is feasible and that
      the survival results are favorable. This treatment strategy should be further
      explored in a phase-III randomized trial.

PMID- 8873160
TI  - Brainstem gliomas in children. A Children's Cancer Group review of 119 cases.
AB  - Brainstem gliomas (BSG) with intrinsic and extensive brainstem involvement
      continue to have a poor outlook despite current treatment approaches.
      Neuroimaging studies have aided in the differentiation of malignant brainstem
      tumors from more 'benign' subgroups. A Children's Cancer Group protocol
      evaluating outcome in children with BSG after treatment with hyperfractionated
      radiotherapy (7,200-7,800 cGy) was recently completed. The clinical aspects of
      119 children entered into this study were reviewed in an attempt to determine
      risk groups and prognostic indicators. The overall survival of this group was
      very poor and there was no statistically significant correlation of survival with
      age, sex, clinical symptoms and signs, or tumor grade. Longer survival was only
      associated with prolonged duration of brainstem symptoms and signs greater than 1
      month prior to diagnosis of the tumor. Improved outlook for children with BSG
      will require further research in tumor biology and newer therapeutic modalities.

PMID- 8873161
TI  - Gamma knife radiosurgery in children.
AB  - 52 pediatric patients were treated with radiosurgery at the University of
      California, San Francisco. Arteriovenous malformations were treated in 27
      patients. Complete obliteration was noted in 4 of 12 patients imaged more than 2
      years after radiosurgery. Arteriovenous malformation rebleed was noted in 1
      patient. Symptomatic T2 changes were noted in 2 patients. Among 29 neoplasms
      treated in 25 patients, local control was noted in 5 of 7 low-grade gliomas, 5 of
      14 high-grade gliomas, 4 of 5 craniopharyngiomas and 3 of 3 sarcomas. Three
      patients treated for neoplasms developed necrosis after radiosurgery.

PMID- 8873162
TI  - Incidence of increased intracranial pressure after early surgical treatment of
      syndromic craniosynostosis.
AB  - The late development of intracranial hypertension after an aesthetically
      successful cranial vault expansion has been noted anecdotally in children with
      syndromic synostosis. If untreated, this process can lead to neurological and
      visual deterioration; however, the frequency of this problem is uncertain. In an
      attempt to detect this process before the onset of irreversible impairment, the
      authors have since 1991 incorporated routine ophthalmological evaluations into
      the multidisciplinary follow-up protocol for all patients with complex
      craniosynostosis. These examinations were performed at initial evaluation and at
      6-month intervals thereafter. The present report focuses on the results in 22
      consecutive infants with syndromic synostosis who underwent initial surgery
      between 1991 and 1994. All but 4 children underwent initial cranial
      reconstruction at 6-18 months of age. Four patients had papilledema
      preoperatively which in each instance resolved postoperatively. During the follow
      up period, 8 children manifested evidence of late intracranial hypertension at a
      median of 16.5 months after initial operation(s): 4 developed asymptomatic
      papilledema, 1 had progressive proptosis, and 3 had other subtle clinical signs
      of increased intracranial pressure (ICP). Further evaluation disclosed a Chiari 1
      malformation in 2 children; 4 had a 'beaten copper' appearance on skull
      radiographs, and 4 underwent lumbar puncture, which in each case demonstrated an
      opening pressure above 20 cm H2O. Only 3 children exhibited symptoms from the ICP
      elevation. Six children with a head size < or = the 25th percentile underwent a
      repeat cranial expansion; after the cranial vault expansion, one child who
      initially had slit-like ventricles developed ventriculomegaly and, because of
      persistent papilledema, underwent insertion of ventriculoperitoneal (VP) shunt.
      Two other patients with a head circumference above the 50th percentile and the
      development of moderate ventriculomegaly underwent VP shunt insertion alone. All
      children have had complete resolution of papilledema as well as other symptoms
      and signs of increased ICP without evidence of optic atrophy or neurological
      sequelae. This study indicates that the incidence of delayed, asymptomatic
      increases in ICP among children with complex craniosynostosis is higher than
      previously estimated. The pathophysiologic bases for this process are discussed.
      Because the detection of this problem at a presymptomatic stage should optimize
      the likelihood of a good functional outcome, we strongly recommend close
      ophthalmological and clinical follow-up as a part of the comprehensive care of
      all young children with complex craniosynostosis, even after a cosmetically
      successful cranial expansion.

PMID- 8873163
TI  - Brain stem gliomas: therapeutic options at time of recurrence.
AB  - Despite contentions to the contrary, the majority of children with recurrent
      brain stem gliomas survive for at least 3 months after first relapse. Treatment
      can be undertaken and response determined, especially if brain stem necrosis is
      taken into consideration. Relatively few patients have been treated on well
      designed studies accruing adequate numbers of patients. No conventional salvage
      therapy exists. Adequate studies with innovation approaches are needed to help
      individual patients, families and future generations of children with brain stem
      gliomas.

PMID- 8873164
TI  - Alternative therapies for children with brain stem gliomas: immunotherapy and
      gene therapy.
AB  - Alternative means are needed for the treatment of childhood brain stem gliomas.
      Both immunotherapy and gene therapy have and will be, in the future, evaluated
      for these patients. Results, to date, with immunotherapy have been sparse and
      variable. Restorative immunotherapy, especially the use of beta-interferon, has
      shown some promising results. However, in one recently completed trial, the
      combination of beta-interferon plus hyperfractionated radiotherapy in newly
      diagnosed patients did not apparently result in improved survival. Gene therapy,
      still in its infancy, also may be potentially applicable to the treatment of
      children with brain stem gliomas.

PMID- 8873165
TI  - Validity of the Borg perceived exertion scale for use in semirecumbent ergometry
      during immersion in water.
AB  - This investigation examined the validity of the Borg 15-category Ratings of
      Perceived Exertion (RPE) scale during semirecumbent exercise in 32 degrees C
      water. 9 men undertook 12 8-min. trials at 3 power outputs and 4 pedal-crank
      rates. The power output was distributed between the arms (20%) and legs (80%).
      RPEs were measured for the arms, legs, chest, and over-all body. Correlation
      coefficients for RPE expressed as a function of power output and gross metabolic
      efficiency (MEG) ranged from .56 to .83 and .54 to .70, respectively, for each
      pedal-crank rate. Validity coefficients were greatest at those pedal-crank rates
      having the highest MEG. The Borg 15-category RPE scale is valid for use during
      semirecumbent exercise in water.

PMID- 8873166
TI  - The temporal distribution of suicides in Baton Rouge.

PMID- 8873167
TI  - Aspartame's effects on behavioral thermoregulation in albino rats.
AB  - Aspartame (L-aspartyl-L-phenylalanine methyl ester) was administered
      intraperitoneally to 9 Sprague-Dawley rats partitioned into 2 studies (4 in Study
      1 and 5 for a replication in Study 2) over a two-year period using a within
      subjects, repeated-measures reversal design. Behavioral thermoregulation was
      assessed in a cold Skinner Box using 5-sec. exposures of microwave radiation
      [Specific Absorption Rate = 0.34 Watts/kg/(mW/cm2)] as reinforcing stimuli under
      a fixed-interval 2-min. schedule of positive reinforcement. Two factorial
      analyses of variance [5 (doses) x 8 (hours)] indicated that the main effect for
      the doses of aspartame (2, 4, 8, 16 mg/kg, and saline control) was not
      significant; yet, the interaction (dose x hours) was significant (p < .05).
      Tentatively, aspartame should not cause an uncomfortable rise in body temperature
      (as sugar can do) when consumed in common substances such as soft drinks, yogurt,
      tea, coffee, etc., in doses commensurate with "hedonic" sweetness.

PMID- 8873168
TI  - Academic performance is not a viable determinant of physical therapy students'
      burnout.
AB  - This study investigated the proposed link between students' academic performance
      and burnout. We found no significant correlations between students' cumulative
      grade point average and ratings of emotional exhaustion, depersonalization, and
      personal accomplishment.

PMID- 8873169
TI  - Dispositional optimism and coping with academic examinations.
AB  - Correlations between scores on dispositional optimism and four categories of
      coping strategies for academic examinations for a group of 248 Hong Kong
      undergraduates were .25 for Self-encouragement and -.20 for Cognitive Avoidance.
      These results lend partial support to the association of adaptive coping and
      optimism, measured by the Life Orientation Test.

PMID- 8873170
TI  - Electromyography and chronic pain: do current electromyographic diagnostic
      techniques discriminate against injured female workers?
AB  - EMG recordings, typically obtained in biofeedback training sessions, tend to
      underestimate actual muscle activity in overweight and female pain patients. If
      unadjusted, these measures will likely result in erroneous diagnostic
      conclusions.

PMID- 8873171
TI  - Laterality patterns and visual-motor coordination of children.
AB  - This study examined the association between laterality patterns of eye-hand and
      eye-foot described as congruent or cross-lateral, and visual-motor coordination
      skill (target throwing and kicking) by 606 4- to 6-yr.-olds. Speculation derived
      from contemporary reports of hand preference and motor coordination provided the
      hypothesis that persons exhibiting congruent patterns of eye and limb laterality
      such as right-eye and hand or right-eye and foot pattern would perform better
      than peers who exhibited other laterality patterns. To the contrary, this study
      yielded no significant differences in motor performance between groups with
      different patterns of preference. In view of past studies and present results,
      additional inquiry seems warranted before any consensus regarding the association
      between laterality and motor coordination can be established.

PMID- 8873172
TI  - Principal components analysis of the Physical Self-Efficacy Scale for a black
      sample.
AB  - Principal components analysis of an intercorrelation matrix for the Physical Self
      efficacy Scale in an all black sample of 320 mostly confirmed the original
      validation study of Ryckman, Robbins, Thornton, and Cantrell who used a wholly
      white sample; however, the analysis identified items with factor loadings at
      criterion on more than one factor, one item that loaded on a different subscale,
      and additional factors. It is unknown whether differences in this sample are
      attributable to race or other influences. Further investigation is suggested.

PMID- 8873173
TI  - Selective impairment of auditory processing in chronic fatigue syndrome: a
      comparison with multiple sclerosis and healthy controls.
AB  - The most consistent deficit observed in individuals with Chronic Fatigue Syndrome
      has been in efficiency of information processing. To examine the possibility of a
      modality-specific impairment, the present study examined subjects with Chronic
      Fatigue Syndrome, multiple sclerosis, and healthy controls on an auditory-versus
      visual-paced serial-addition test. 20 subjects with Chronic Fatigue Syndrome, 20
      subjects with clinically definite Multiple Sclerosis, and 20 sedentary healthy
      controls were compared. One-half of the subjects in each group were administered
      the Paced Auditory Serial Addition Test and the other half were administered the
      Paced Visual Serial Addition Test. The group with Chronic Fatigue Syndrome was
      differentially impaired on the auditory relative to the visual processing task.
      The group with Multiple Sclerosis was equally impaired on both versions of the
      task. The results are discussed within the framework of Baddeley's model of
      working memory.

PMID- 8873174
TI  - The growing-louder effect in short diotic stimuli.
AB  - Previous evidence from short monotic stimuli shows that a steady stimulus is
      perceived as growing louder; to be perceived as steady, the intensity of the
      stimulus must decrease. In the present study, 10 subjects heard a sequence of
      diotic tonal stimuli. Each stimulus lasted 1.5 sec. and increased, decreased, or
      remained steady in intensity; initial intensity was 40 dB SPL and carrier
      frequency was 1 kHz. Subjects made forced binary responses of "growing louder" or
      "growing softer" to each stimulus. Confirming the evidence from monotic stimuli,
      the mean value of changing intensity eliciting equal numbers of both responses
      was negative. Possible explanations for this growing-louder effect reside in (a)
      the percussive nature of many natural sounds and (b) selective responding to
      approaching sound-sources.

PMID- 8873175
TI  - Individual differences in body temperature assessed by a two-term function.
AB  - A new approximation, an alternative to the cosine function, was used to analyze
      body temperature throughout the day. The model studied is a two-term function
      characterized by three parameters that describe the temperature rise and fall. In
      contrast to other cyclic functions, this function can easily model complete
      cycles as well as segments of a cycle. This function has been applied to
      temperature series validating the dimension of morningness-eveningness throughout
      the day and also to studies that include body temperature, personality factors,
      and the dimension of morningness throughout a complete circadian period.

PMID- 8873176
TI  - Language style and evaluation of a female speaker.
AB  - This study examined the effect of style of speech ("tentative" vs assertive) used
      by a female speaker upon the evaluations made by college students. Both men and
      women evaluated the assertive speaker more favorably than the tentative speaker.
      The hypothesis that men would devaluate the assertive woman was not supported.

PMID- 8873178
TI  - Specificity and variability of practice with young children.
AB  - It has previously been suggested that paradigms investigating schema theory
      should include tests of the effects of variability of practice on tasks
      experienced during the acquisition of learning. The present aim was to test this
      effect using a sports-related task. Two groups of children (n = 13 each) aged
      between 3 and 5 yr. old were pretested on an aiming task. They then received ten
      practice trials per day for ten days. One group (designated the specific group)
      practised only at the specified target distance, while another group (designated
      the specific plus variable group) practised at the target distance and at
      distances around the target. At the end of the practice period both groups were
      again tested. The data were analysed for distance and lateral errors, using two
      way (group x time) analyses of covariance with one repeated measure on the latter
      factor. The interaction of groups x time was significant for the distance errors,
      indicating that at the end of the practice period the specific plus variable
      group had improved more than the specific group. This finding extends previous
      work on a similar variability paradigm to a sports-related setting.

PMID- 8873179
TI  - The slope method for prescribing exercise with ratings of perceived exertion
      (RPE).
AB  - The Borg Ratings of Perceived Exertion scale (RPE) has been shown to be a
      valuable tool for prescribing exercise; however, use of RPE-based exercise
      prescriptions in field settings has often been problematic because RPE data
      derived from maximal exercise testing are needed. We describe a simple method for
      obtaining target RPEs for exercise training from submaximal exercise data. Target
      RPEs for 50%, 60%, 70%, and 85% VO2 peak exercise intensities obtained using the
      new method did not differ significantly from those obtained using data from a
      maximal graded exercise test. The mean difference was less than one RPE unit and
      was not significant (p < .05). Therefore, the Slope Method appears to be valid
      for developing RPE-based exercise prescriptions.

PMID- 8873180
TI  - An analysis of students' reasons for studying martial arts.
AB  - Responses to a questionnaire study of initial reasons to study martial arts by
      170 students in a school of martial arts are described. Although self-defense and
      physical fitness motives were prominently claimed, further analyses of more
      subtle existential and psychological issues are warranted.

PMID- 8873181
TI  - French adaptation of the Ways of Coping Checklist.
AB  - A short form (42 items) of the Ways of Coping Checklist was administered to 468
      French men and women. A factor analysis of the responses yielded three factors,
      accounting for about 35% of the total variance, and named Problem-focused Coping,
      Emotion-focused Coping, and Social Support seeking. The first two dimensions are
      close to those generally described in the literature. Some interesting
      relationships of scores appeared between personality and coping, notably, between
      anxiety and emotion-focused coping.

PMID- 8873182
TI  - Dysphoria and the failure to perceive and use discounting information:
      implications for internalizing negative feedback.
AB  - The present study examined the proposition that dysphoric individuals make
      internal attributions because they do not use available discounting cues. To test
      this hypothesis, 23 dysphoric and 32 nondysphoric college students were either
      provided a discounting cue or were led to believe that an internal attribution
      for failure was appropriate (no discounting cue). On the primary measure of
      internality, nondysphoric individuals made greater external attributions when a
      discounting cue was available than they did when no such cue was present, but
      attributions made by dysphoric individuals were unaffected by the presence of a
      discounting cue. On the other hand, using a secondary dependent measure inserted
      to replicate a prior study in this area, key comparison differences were not
      obtained.

PMID- 8873183
TI  - Value of self-identification of hearing loss in a screening program for older
      adults.
AB  - During auditory screening, 100 adults over age 65 were asked to self-identify the
      presence of a hearing loss. Most saying "no" to the presence of a loss passed the
      hearing and communication screening while those who said "yes" were more at risk
      for failure on both.

PMID- 8873184
TI  - A comparative study of color preferences in Japan, China and Indonesia, with
      emphasis on the preference for white.
AB  - To measure and compare the main color-preference tendencies in Japan, China, and
      Indonesia, 490 subjects (175 Japanese, 158 Chinese, and 157 Indonesian) were
      asked to choose from a color chart the three colors they liked most and the three
      they liked least and to state the reasons for their choices. Analysis of the
      choices by correspondence analysis showed that each area (country) shows
      tendencies for unique color preference and that there are statistically
      significant differences in the frequency of selection of colors of certain hues
      and tones. However, a high preference for white was common to all areas, along
      with preferences for some other colors. The successive studies done by the author
      have shown a common strong preference for white in other Asian areas as well. The
      reasons given for the choices suggested that associative images based on
      environmental and cultural aspects may be important influences on color
      preference.

PMID- 8873185
TI  - Perceptual responses to deep water running and treadmill exercise.
AB  - Perceived exertion during deep water running and treadmill exercise was measured
      to examine gender and mode specific responses. Deep water running to VO2 peak was
      performed in 3-min. stages at leg speeds controlled by a metronome. Treadmill
      exercise was performed at matched leg speeds. VO2 and heart rate were
      continuously monitored by open circuit spirometry and radiotelemetry. Perceived
      exertion was measured using Borg's 6-20 point scale. Statistical analyses were
      performed using multiple linear regression with dummy coded discrete variables.
      Ratings of perceived exertion were significantly higher during deep water running
      when exercising at equal leg speeds. Mean rated perceived exertion at each stage
      of the test for either exercise mode was not significantly different between men
      and women.

PMID- 8873186
TI  - Smooth pursuit eye movements and stimulus predictability in children: a reply to
      Haishi and Kokubun.
AB  - This reply to Haishi and Kokubun's study of smooth pursuit in young children
      points out that the quality of pursuit as it pertains to predictability is
      confounded with the immaturity of visual system structure. Two possible solutions
      to the confounding are discussed.

PMID- 8873187
TI  - Emotional information processing and visual evoked brain potentials.
AB  - Visual evoked potentials to emotional slides presented for 2 sec. were
      investigated in 13 subjects. 73 emotional slides (pleasant, unpleasant, and
      neutral) were selected from a standardized set of photographic slides, the 1988
      International Affective Picture System of Lang, Ohman, and Vaitl Visual evoked
      potentials were recorded from three head locations, frontal, central and parietal
      (Fz, Cz, and Pz). Analyses were performed in the two latency ranges: 300-400
      msec. and 400-500 msec. Analyses showed an arousal effect, as indicated by a
      quadratic trend, indicating that emotional slides (both pleasant and unpleasant)
      gave higher cortical positivity than neutral ones, for all components. In
      addition, in the two latency epochs, larger positivities were found at Pz,
      compared to Fz and Cz, whereas Fz and Cz did not differ from each other.

PMID- 8873188
TI  - Physiological correlates with perceived exertion during deep water running.
AB  - The purpose of this study was to investigate the relationship between perceived
      exertion and physiological variables during deep water running. Deep water
      running to VO2 peak was performed in 3-min. stages at leg speeds controlled by a
      metronome. VO2 and heart rate were continuously monitored by open circuit
      spirometry and radiotelemetry. Perceived exertion was measured using Borg's 6 to
      20-point scale. Multiple regression analysis with a forward solution was used to
      establish the relations of the measures of perceived exertion with the measures
      of oxygen uptake, carbon dioxide production, pulmonary ventilation, respiratory
      exchange ratio, and respiratory rate. %VO2 max was the most important variable
      predicting perceived exertion. Men and women (ns = 12) reported using different
      sensory cues to perceive exertion during deep water running.

PMID- 8873189
TI  - Effects of masked repetition priming and orthographic neighborhood in visual
      recognition of words.
AB  - The role of orthographic neighborhood (neighborhood size and neighborhood
      frequency) in visual-word recognition was analyzed using the masked repetition
      priming paradigm. Specifically, we varied stimulus-onset asynchrony (33, 50, and
      67 msec.) and type of prime (identical, unrelated, unprimed) in a lexical
      decision task. Analyses show additive effects of repetition and stimulus-onset
      asynchrony. Further, the unrelated condition overestimated the repetition effects
      relative to an unprimed condition. Facilitatory effects of neighborhood size and
      inhibitory effects of neighborhood frequency were also found. The results are
      interpreted in terms of current models of visual-word recognition.

PMID- 8873190
TI  - Assessment of understanding by people manifesting mental retardation: a
      preliminary report.
AB  - An analysis of the psychological aspects of the legal concept of
      competency/fitness to stand trial draws attention to the central role of
      understanding. The rationale of certain basic requirements for the construct
      validity of a psychometric test of understanding in people with mental
      retardation is presented, and a test that meets those requirements is described.

PMID- 8873191
TI  - Burnout and managers' tactics of influence.
AB  - This research focused on whether perception of burnout, measured by the Cherniss
      Burnout Scale, is related to managers' self-reported tactics of influence with
      subordinates. Contrary to expectations, analysis of the scores of 209 managers
      from 47 organizations indicated rational, ingtratiating, and inspirational
      appeals, consulation, and exchange tactics of influence were positively
      correlated with burnout, whereas scores on pressure and legitimacy were
      negatively correlated with burnout, scores. Limitations of the study were also
      mentioned.

PMID- 8873192
TI  - Role of intelligence tests in speech/language referrals.
AB  - This study examined the relation of the WISC-R Verbal IQ with measures of oral
      and written language among 190 students referred to a private educational clinic
      over a 5-yr. period. Correlations of Verbal IQ with scores on measures of oral
      language, written language, receptive language, reading comprehension, and basic
      reading skills were calculated for the total sample and by Grades 1-3, 4-7, and 8
      11. Standard regression coefficients were used to estimate the proportion of
      variance explained by these five measures. Significant correlations were found
      for Verbal IQ with the measures, ranging from .36 (Basic Reading Skills) to .69
      (Receptive Vocabulary). Multiple regression indicated that 59% of the variance
      was explained by the five measures and that three--Oral Language, Receptive
      Vocabulary, and Reading Comprehension--contributed significantly to Verbal IQ.
      Correlations across grades showed inconsistent differences by grade for Verbal IQ
      with language variables. Implications for speech-language referral practices are
      discussed.

PMID- 8873193
TI  - Misrepresentation of sleep-laboratory dream research with children.
AB  - A recent article by Resnick, et al. misrepresents the methods and findings of
      sleep-laboratory dream research with children, and, hence, the significance of
      their own findings. Since these misrepresentations remain almost totally
      unretracted, I here undertake to correct them, so that the literature more
      accurately may reflect the current status of laboratory studies of children's
      dreaming.

PMID- 8873194
TI  - A multidisciplinary investigation of the relation of state sport confidence with
      preference and velocity of swimming starts.
AB  - This study investigated the relations of state sport confidence with preference
      of swimming start, i.e., pike or flat, and vertical velocity for male and female
      NCAA Division I swimmers. Ten male and 10 female swimmers who had a minimum of
      five years competitive swimming experience participated. Men generated greater
      vertical velocity on both the pike and flat starts. Analyses of variance
      indicated a relationship foc gender with the most confident swimming start and
      vertical velocity for the pike and flat starts. In addition, a significant
      interaction between gender, preferred swimming start, and most confident swimming
      start was found. Discriminant function analysis using gender as the grouping
      variable and the dependent variables of vertical velocity and state sport
      confidence indicated that gender was an indicator of swimmers' performance and
      state sport confidence on the pike and flat starts.

PMID- 8873195
TI  - Gender differences in physical fitness in old age.

PMID- 8873196
TI  - Elevation of core temperature and mental functioning.
AB  - The purpose of this study was to investigate whether raised core temperature due
      to gradually increased amounts of exercise affects concentration and speed of
      information processing, 20 paid men, separated into groups of high (> 56
      ml/kg/min.) and low fitness (< 46 ml/kg/min.) according to their maximal oxygen
      uptake (VO2max), participated in two experimental conditions (exercise and
      control). Concentration was measured by the Random Number Generation test of
      attentional deployment given every 10 min. of cycling at workloads calculated as
      40, 50, 60, 70, and 80% of individual VO2max values and 10 min. after exercise
      cessation (exhaustion). Speed of information processing was estimated by an eight
      choice reaction time/movement time task given before and after exercise and 15
      min. after exercise cessation. Core temperature was recorded at the same time
      individuals were administered the psychological tests. Analyses indicated that
      core temperatures increased significantly as a function of exercise intensity for
      high and low fitness groups. Correlations among the psychophysiological factors
      indicated that increases in core temperature were not associated with mental
      functioning. However, at certain core temperatures, core temperature and average
      choice reaction time/movement time were associated with participants' fitness.

PMID- 8873197
TI  - Viewing music videotapes during exercise and ratings of perceived exertion.
AB  - 30 men 18 to 25 years of age participated in two treatments presented in
      counterbalanced order. They exercised for 6 min. on a Monarch cycle ergometer at
      a workload of 122.5 W while viewing and listening to music videotapes or
      exercised in a quiet environment. External stimuli in the viewing and listening
      to music videotapes did not distract subjects from assessing their exertion
      during exercise.

PMID- 8873198
TI  - Learning test on expressive phonetic symbolism.
AB  - We asked 249 students to learn three different vocabulary lists, each containing
      19 word pairs (Indonesian, Suaheli, and one mixed list composed of items from 13
      different languages) in three versions: "normal" (factual classification),
      "reversed" (opposite classification), and "disarranged" (word meaning imputed in
      a completely different dimension). That those word-pairs with "normal"
      classification would lead to best learning was not generally confirmed but was
      corroborated for favourable learning conditions (items at the top of the list,
      items at the beginning of the questioning, easy to learn items), whereas the
      effect of phonetic symbolism combined with "normal" presentation proved rather
      abstruse. We assume that in the latter cases encoding worked rather
      automatically, and additional information used energy. The encoding process uses
      so much energy that further information is not useful under unfavourable learning
      conditions. We found a relation between performance on each mode of presentation
      and sex. Independent of presentation mode, learning depends on age, sex,
      membership in a seminar, and subject matter studied. Therefore, we examined the
      distribution of these in our nine groups (three languages by three versions).
      Since no statistically relevant differences in distribution arose, our results do
      not have to be qualified.

PMID- 8873199
TI  - Voice and advertising: effects of intonation and intensity of voice on source
      credibility, attitudes toward the advertised service and the intent to buy.
AB  - Voice has been neglected in research on advertising and attitude change. In an
      experiment with 2 x 2 x 2 factorial design (N = 279), several hypotheses derived
      from the Elaboration Likelihood Model and from phonetic literature were tested; 2
      linguistically similar advertising messages on financial services of high
      (student loan) versus low (Automatic Teller Machine cards) involvement are
      recorded by a professional actor using 4 types of voice (2 levels of intonation
      of voice x 2 levels of intensity). Analysis by a system of simultaneous equations
      indicated that the effects of voice are different under low and high involvement.
      Intensity of voice affects credibility of the source significantly more under low
      than high involvement; intonation of voice affects credibility more under high
      than low involvement. Unexpectedly, characteristics of voice affect attitudes
      toward the advertised service and intent to buy.

PMID- 8873200
TI  - Asymmetries of facial motility during the dissimulation of emotion.
AB  - The asymmetrics of facial expression were estimated in a sample of 14
      experimental subjects with the Facial Action Coding System during voluntary
      control of facial mimicry while viewing videotapes. The subjects were instructed
      to express facially the emotion experienced or to dissimulate their true emotion
      with a facial expression opposite (incongruous) to what they actually felt. Only
      during dissimulation did facial mimicry show an asymmetric distribution toward
      the lower left side of the face.

PMID- 8873201
TI  - Grip strength and intertrial rest.
AB  - This experiment illustrates that the 1991 Montazer and Thomas conclusion that
      grip strength declines over time is incomplete 15 men performed 4 grip-strength
      trials with intertrial rests of 120 sec. Analysis showed that performance did not
      decrease over the 4 trials, on the contrary, the pattern was that of a learning
      curve, with a significant difference across the 4 trials, i.e., on Trial 1 grip
      strength was lower than on successive trials. Such a result points to the
      importance of 'warming-up' the muscle to obtain optimum functioning. Also,
      subjects should be familiar with the task and the equipment to reduce the chance
      of a Type I error. Implications for research are discussed.

PMID- 8873202
TI  - The total-time hypothesis and the acquisition of connected discourse as a
      function of mode of presentation, presentation rate, and intelligence.
AB  - This study investigated the applicability of the total-time hypothesis in
      learning connected discourse as a function of two separate modes of presentation,
      two different presentation rates, and two significantly different level of adult
      intelligence. The eight paragraphs of the Nelson-Denny Reading Test (Form A)
      served as the connected discourse. Statistical analyses showed the total-time
      hypothesis to be definitely applicable to the learning of the connected discourse
      Substantial doubt regarding the wisdom of using compressed speech technology as
      an educational panacea was evident.

PMID- 8873203
TI  - An increase in cortical excitability with no change in spinal excitability during
      motor imagery.
AB  - During motor imagery, to estimate changes in excitability of flexor carpi
      radialis muscle motoneurons of the spinal and cortical levels, electrical stimuli
      for recording H-reflex and transcranial magnetic stimulation (TMS) for recording
      motor evoked potentials (MEPs) were used. In the absence of movement or
      detectable EMG activity during motor imagery, there was an increase in cortical
      excitability with no change in spinal excitability.

PMID- 8873204
TI  - Alexithymia and visual perception.
AB  - 60 subjects were administered the Toronto Alexithymia Scale-20, a screening test
      for alexithymia, and categorized by the usual scoring procedure. Each subject was
      then given the six Performance subtests of the Wechsler Adult Intelligence Scale
      Revised which address aspects of visual perception, organization, and
      construction. Analysis indicated that the alexithymic group scored significantly
      lower on two tests of visual perception, Picture Completion and Digit Symbol of
      the Wechsler Adult Intelligence Scale-Revised.

PMID- 8873205
TI  - Youth cohort size and suicide rates.
AB  - Youth suicide rates by state in 1970 were positively associated with their
      proportion in the population but not in 1989. Changes in the youth suicide rate
      over the 20-yr. period were not associated positively with changes in their
      cohort size.

PMID- 8873206
TI  - A validity study of the social skills rating system-teacher version with disabled
      and nondisabled preschool children.
AB  - This study examined the differences among social skills and problem behaviors of
      disabled (n = 22) and nondisabled (n = 27) preschoolers on Social Skills Rating
      System-Teacher Version. Significant differences were found between the two groups
      on all measures of social skills and all but one measure (internalizing problems)
      of problem behaviors. Also, correlations with a measure of social competence and
      8 teachers' ratings strongly supported the validity of this measure of social
      skills for preschool children. Implications for designing early intervention
      programs are discussed.

PMID- 8873207
TI  - Effect of viewing the RPE scale on the ability to make ratings of perceived
      exertion.
AB  - 7 subjects exercised while viewing and not viewing the Rating of Perceived
      Exertion scale during exercise to assess whether ratings of perceived exertion
      are influenced by viewing the scale itself. Analysis suggested that monitoring
      moderate to high intensity exercise without viewing the RPE scale may result in
      an underestimation of exertion.

PMID- 8873208
TI  - Evaluation of a simulation of human performance on random-digit generation:
      measures of concept and redundancy.
AB  - Ginsburg and Karpiuk in 1995 introduced an algorithm that simulates human
      performance in tasks of generating random digits. We have compared sequences
      produced by this algorithm with human performance and truly random sequences. It
      is shown that the algorithm can be used to simulate human performance according
      to the measures on which it had been constructed. However, other peculiarities of
      human performance are not captured by the algorithm. The results are discussed
      with regard to current theories of human random digit generation.

PMID- 8873209
TI  - Demands during maze. learning in limbic epileptic rats: selective damage in the
      thalamus?
AB  - A qualitatively evident enhancement of chromolytic neurons within the lateral
      posterior thalamus of rats in which limbic seizures had been induced by lithium
      and pilocarpine and who were later trained for spatial memory was assessed
      quantitatively. The significant increase in the numbers of chromolytic neurons
      and the decrease in the numbers of normal neurons for these rats compared to the
      reference brains suggested these morphological changes were recent. The
      hypothesis that excessive stimulation of the lateral posterior nucleus by daily
      training in a radial maze may have facilitated the necrosis was supported by the
      inverse relationship between a linear combination of the numbers of normal
      neurons and oligodendroglia and the rate of learning during the earlier but not
      the later sessions. An implication for iatrogenic effects from rehabilitation of
      humans following brain injury was suggested.

PMID- 8873210
TI  - Lucid dreaming and the mind-body relationship: a model for the cognitive and
      physiological variations in rapid eye movement sleep.
AB  - The psychophysiological properties of the lucid dream state were examined to
      evaluate the relationship between lucid and nonlucid dreaming, emphasizing the
      fact that the components of self-reflectiveness and other cognitive features
      commonly associated with lucid dreams occur in all dreams to various extents.
      Although lucid dreams are clearly toward one end of the continuum, they still
      share many of the characteristics present in most dreams. In this respect,
      exploration of lucid dreams may not necessarily be a misguided path toward the
      understanding of dreaming in general. A simple model was described to illustrate
      the mind-body relationship in various forms of REM dreaming.

PMID- 8873211
TI  - Amount of psychological stress reported by high school volleyball officials.
AB  - All volleyball officials registered with a state high school activities
      association in a midwestern state were surveyed at the end of the volleyball
      season to assess their self-reported, psychological stress. Of 470 officials
      contacted, 353 (75%) responded by filling out a simple 5 point rating scale. The
      mean rating of stress was 2.3 (SD = .6) (between "very little" and "a moderate
      amount") which is similar to past findings for certified, amateur baseball and
      softball umpires.

PMID- 8873212
TI  - The effect of preference for three different types of music on magnitude
      estimation-scaling behavior in young adults.
AB  - The purpose of the present study was to assess the effect of preference for three
      different types of music on magnitude estimation scaling behavior in young
      adults. Three groups of college students, 10 who liked rock music, 10 who liked
      big band music, and 10 who liked classical music were tested. Subjects were
      instructed to assign numerical values to a random series of nine suprathreshold
      intensity levels of 10-sec, samples of rock music, big band music, and classical
      music. Analysis indicated that subjects who liked rock music scaled that stimulus
      differently from those subjects who liked big band and classical music. Subjects
      who liked big band music scaled that stimulus differently from those subjects who
      liked rock music and classical music. All subjects scaled classical music
      similarly regardless of their musical preferences. Results are discussed in
      reference to the literature concerned with personality and preference as well as
      spectrographic analyses of the three different types of music used in this study.

PMID- 8873213
TI  - Is interhemispheric connectivity reduced after callosotomy? A critique.
AB  - A recent case report of interhemispheric correlational measures in a
      callosotomized patient by Corsi-Cabrera, Trias, Guevara, Haro, and Hernandez in
      1995 provided evidence taken by the authors of the study to suggest that the
      corpus callosum may not be crucial to interhemispheric coupling. This conclusion
      was proposed even though (1) presurgical correlation measures necessary for
      evaluating coherence changes produced by surgery were not available for this
      subject and (2) previous studies presenting evidence inconsistent with their
      conclusions were not discussed. In view of these two shortcomings, the authors'
      conclusion concerning callosal function may be premature.

PMID- 8873214
TI  - Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and
      molecular mechanisms.
AB  - Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurines
      such as mercaptopurine and thioguanine. TPMT activity exhibits genetic
      polymorphism, with about 1 in 300 inheriting TPMT-deficiency as an autosomal
      recessive trait. If treated with standard dosages of thiopurines. TPMT-deficient
      patients accumulate excessive thioguanine nucleotides (TGN) in hematopoietic
      tissues, leading to severe hematopoietic toxicity that can be fatal. However,
      TPMT-deficient patients can be successfully treated with a 10-15-fold lower
      dosage of these medications. The human gene encoding polymorphic TPMT has been
      cloned and characterized, and two mutant alleles have recently been isolated from
      TPMT-deficient and heterozygous patients (TPMT*2, TPMT*3), permitting development
      of PCR-based methods to identify TPMT-deficient and heterozygous patients prior
      to therapy. TPMT*3 is the predominant mutant allele in American whites,
      accounting for about 75% of mutations in this population. Ongoing studies aim to
      better define the influence of TPMT activity on thiopurine efficacy, to identify
      additional mutant alleles and determine their frequency in different ethnic
      groups, to elucidate the mechanism(s) for loss of function of mutant proteins, to
      identify potential endogenous substrates and to define the molecular mechanisms
      of TPMT regulation. Together, these advances bold the promise of improving the
      safety and efficacy of thiopurine therapy.

PMID- 8873215
TI  - Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice
      deficient in CYP1A2.
AB  - We investigated the involvement of CYP1A2 in the pharmacokinetics and metabolism
      of caffeine using mice lacking its expression (CYP1A2 -/-). The half-life of
      caffeine elimination from blood was seven times longer in the CYP1A2 -/- than
      wild-type mice. The clearance was concomitantly eight times slower. No parameter
      that could affect the pharmacokinetics differed between CYP1A2-/-and wild-type
      mice such as creatinine for kidney function; alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase and bilirubin for liver function; or
      albumin for protein binding. Other P450s CYP2A, 2B, 2C, 2EI, and 3A were also
      unchanged in the knockout animals. Caffeine 3-demethylated metabolites thought
      previously to be characteristic of CYP1A2 (especially 1-methylxanthine and I
      methylurate) were also found in the urines of the CYP1A2-/-animals, although at
      40% of the level found in wild-type mice. These data indicate that the clearance
      of caffeine in wild-type mice is primarily determined by CYP1A2.

PMID- 8873216
TI  - Increased prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2)
      in obesity with comorbid substance use disorder: a preliminary report.
AB  - In order to investigate the prevalence of the Taq I A1 allele of the dopamine
      receptor gene (DRD2) in obesity with and without comorbid substance use disorder,
      a total of 40 patients, from an outpatient neuropsychiatric clinic in Princeton,
      New Jersey, were genotyped for presence or absence of the Taq I DRD2 A1 allele.
      The primary inclusion criterion for 40 obese subjects was a body mass index (BMI)
      equal to or over 25 (uncharacterized); 11 obese subjects had severe substance use
      disorder; 20 controls had a BMI below 25; and, 33 substance use disorder (less
      severe) patients had a BMI below 25. The data were statistically compared with
      three different sets of controls divided into three separate groups (Group I, n =
      20; Group II, n = 286; Group III, n = 714). They differed according to screening
      criteria (drug, alcohol, nicotine abuse/dependence, BMI below 25 and other
      related behaviours including parental history of alcoholism or drug abuse and DSM
      IV, Axis I and Axis II diagnoses). Groups II and III were population controls
      derived from the literature. The prevalence of the Taq I A1D2 dopamine receptor
      (DRD2) alleles was determined in 40 Caucasian obese females and males. In this
      sample with a mean BMI of 32.35 +/- 1.02, the A1 allele of the DRD2 gene was
      present in 52.5% of these obese subjects. Furthermore, we found that in the 23
      obese subjects possessing comorbid substance use disorder, the prevalence of the
      DRD2 A1 allele significantly increased compared to the 17 obese subjects without
      comorbid substance use disorder. The DRD2 A1 allele was present in 73.9% of the
      obese subjects with comorbid substance use disorder compared to 23.5% in obese
      subjects without comorbid substance use disorder. Moreover, when we assessed
      severity of substance usage (alcoholism, cocaine dependence, etc.) increasing
      severity of drug use increased the prevalence of the Taq I DRD2 A1 allele; where
      66.67% (8/12) of less severe probands possessed the A1 allele compared to 82%
      (9/11) of the most severe cases. Linear trend analyses showed that increasing use
      of drugs was positively and significantly associated with A1 allelic
      classification (p < 0.00001). These preliminary data suggest that the presence of
      the DRD2 A1 allele confirms increased risk not only for obesity, but also for
      other related addictive behaviours (previously referred to as the Reward
      Deficiency Syndrome) and that a BMI over 25 by itself (without characterization
      of macroselection or comorbid substance use disorders) is not a sufficient
      criterion for association with the DRD2 A1 allele.

PMID- 8873217
TI  - Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential
      association with Tourette syndrome, substance abuse and other disorders.
AB  - Defects in serotonin metabolism, and abnormalities in both blood serotonin and
      tryptophan levels, have been reported in many psychiatric disorders. Tryptophan
      2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of
      tryptophan to N-formyl kenurenine. Functional variants of this gene could account
      for the observed simultaneous increases or decreases of both serotonin and
      tryptophan in various disorders. We have identified four different polymorphisms
      of the human TDO2 gene. Association studies show a significant association of one
      or more of these polymorphisms and Tourette syndrome (TS), attention deficit
      hyperactivity disorder (ADHD) and drug dependence. The intron 6G-->T variant was
      significantly associated with platelet serotonin levels. Only the association
      with TS was significant with a Bonferroni correction (p = 0.005). Our purpose
      here is not to claim these associations are proven, but rather to report
      preliminary results and show that easily testable polymorphisms are available. We
      hope to encourage additional research into the potential role the TDO2 gene in
      these and other psychiatric disorders.

PMID- 8873218
TI  - Characterization and PCR-based detection of two different hybrid CYP2D7P/CYP2D6
      alleles associated with the poor metabolizer phenotype.
AB  - The majority of humans deficient in the cytochrome P450 CYP2D6 enzyme, so-called
      poor metabolizers (PMs), can now be identified by genotyping for several
      different PM-associated mutations. However, additional null alleles remain to be
      identified as demonstrated by subjects with the PM phenotype in the absence of a
      corresponding genotype. The rare 11 kb band on Xba I RFLP analysis, which is
      distinct from the 13 kb CYP2D6D (CYP2D6*5) allele, has been proposed to
      constitute such a unique non-functional allele. Here we demonstrate that the 11
      kb band represents at least two different nine exon CYP2D7P/CYP2D6 hybrids
      generated by large deletions in the CYP2D gene cluster due to unequal cross-over
      or looping-out mechanisms. The total allele frequency was approximately 0.001
      0.01 in European and North American Caucasians. The most common variant
      (CYP2D6*16) had breakpoints lying between the end of exon 7 and the start of exon
      9 of the respective genes. The "CYP2D7-like' part of the gene was most homologous
      to the previously described CYP2D7AP and CYP2D7 (44/11.5) sequences. The other
      chimeric allele consisted of exon 1 of CYP2D7 and exons 2-9 from CYP2D6, and may
      be similar to a hybrid gene termed CYP2D6*13 recently described in a French
      individual. Two different routine PCR assays were developed for rapid and
      sensitive detection of these alleles, namely amplification of a 8 kb fragment
      from both CYP2D6*13 and CYP2D6*16, together with a CYP2D6*16-specific method
      which gave a 1.4 kb PCR product. The 8 kb assay for the CYP2D6*13 and CYP2D6*16
      alleles also produced a 9.5 kb fragment in samples positive for the 13 kb
      CYP2D6*5 allele. Therefore, it is now possible to screen for the large CYP2D gene
      deletions by a single long PCR method.

PMID- 8873219
TI  - CYP2C19 genotyping and associated mephenytoin hydroxylation polymorphism in a
      Canadian Inuit population.
AB  - The CYP2C19-associated oxidation polymorphism of mephenytoin was investigated in
      an Inuit population living in the high Arctic of Canada. Results were obtained
      for 152 subjects, of whom 90 were unrelated to first degree relatives.
      Phenotyping was based on the capillary gas chromatographic determination of the
      S/R enantiomeric ratio in overnight urine collected after a dose of 100 mg (R,S)
      mephenytoin. The phenotype was confirmed by determining the S/R enantiomeric
      ratio after acid treatment of urine samples, and for some subjects, by
      determining urinary recovery of 4'-hydroxymephenytoin using capillary
      electrophoresis analysis. DNA was analysed for the m1 and m2 mutations of
      CYP2C19. Three of 152 subjects (2.0%; 95% confidence limits: 0.0-4.2%) were
      phenotypically classified as poor metabolizers (PMs). Genotype analysis
      characterized three individuals as homozygous, and 28 individuals as heterozygous
      for the m1 mutation, the remaining individuals being homozygous for the wild-type
      allele. The genotype of the three PMs was concordant with that of the phenotype.
      DNA fingerprinting confirmed that these three individuals were genetically
      unrelated. The allele frequency of the CYP2C19m1 mutation, determined in
      unrelated subjects, was 0.12 (95% confidence limits: 0.07-0.17). CYP2C19m2 was
      not detected in this population. Thus, the Canadian Inuit resemble Caucasian
      rather than Asian populations in both the incidence of PM phenotype and the
      molecular basis of the polymorphism.

PMID- 8873220
TI  - The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism.
AB  - Tolbutamide undergoes hydroxylation in humans via a cytochrome P450-mediated
      pathway. The primary P450 isozyme responsible for this metabolism is thought to
      be CYP2C9. Population studies have indicated the existence of slow metabolizers
      of tolbutamide (approximately 1 in 500) suggesting a rare polymorphism associated
      with 2C9. Several allelic variants of 2C9 have been identified; however, the
      effect of these allelic variations on metabolism in vivo is not established. In
      the present study, the coding regions, intron-exon junctions, and upstream region
      of CYP2C9 were amplified by PCR and sequenced in two slow metabolizers. One
      individual was homozygous for Leu359/Leu359 and the other individual was
      heterozygous for Arg144/Cys144 and for Ile359/Leu359. No other genetic variations
      in 2C9 were detected in these individuals. PCR-RFLP tests showed that Arg144
      Tyr358 Ile359 Gly417 is the principle CYP2C9 allele. Frequencies of the rarer
      Leu359 and Cys144 alleles were 0.06 and 0.08, respectively, in a Caucasian
      American population and 0.005 and 0.01 respectively in African-Americans. The
      frequency of the Leu359 allele was 0.026 in Chinese-Taiwanese, but the Cys144
      allele was not detected in this population. Studies in a recombinant yeast
      expression system showed that the Leu359 variant had the highest Km and the
      lowest Vmac for hydroxylation of tolbutamide of all the CYP2C9 allelic variants.
      This allelic variant also had the highest Km for the 7-hydroxylation of S
      warfarin. The present data suggest that the incidence of the Leu359 allelic
      variant of CYP2C9 may account for the occurrence of poor metabolizers of
      tolbutamide.

PMID- 8873221
TI  - PCR-based genotyping for duplicated and deleted CYP2D6 genes.
AB  - The debrisoquine hydroxylase (CYP2D6), which metabolizes more than 30 different
      drugs, is highly polymorphic. In subjects having either very low or very high
      enzyme activity, drug therapy at recommended doses using CYP2D6 substrates may
      lead to either increased risk of side effects or therapeutic failure. We here
      describe PCR-based methods for detection of alleles having either duplicated,
      multiduplicated or deleted active CYP2D6 genes. As a control reaction, the entire
      coding region of the CYP2D6 gene is amplified. In conjunction with analysis of
      common mutations using this product as a template, the methods described can be
      used for genotyping of individuals being either poor, intermediate rapid, normal
      or ultrarapid metabolizers and provides an efficient tool for individualization
      of drug therapy.

PMID- 8873222
TI  - Genetic polymorphism of S-mephenytoin 4'-hydroxylation in African-Americans.

PMID- 8873223
TI  - Polymorphism in the human O6-methylguanine-DNA methyltransferase gene detected by
      PCR-SSCP analysis.

PMID- 8873224
TI  - The GSTM1 genetic polymorphism in healthy Saudi Arabians and Filipinos, and Saudi
      Arabians with coronary atherosclerosis.

PMID- 8873225
TI  - Promoter region analysis of the rat CYP2B1 and CYP2B2 genes.

PMID- 8873226
TI  - A retroviral element in the human CYP2D gene cluster.

PMID- 8873228
TI  - Health-related quality of life assessments in osteoarthritis during NSAID
      treatment.
AB  - There is some evidence that nabumetone (1000 mg once daily) in comparison with
      piroxicam (20 mg once daily) in patients with OA in general practice is
      associated with a lower incidence and less severe occurrence of stomach pain but
      with more withdrawals due to lack of efficacy. The aim of this analysis was to
      investigate whether these differences are reflected in health-related quality of
      life assessments. Patients (n = 198) included in this study were selected in
      general practice according to a protocol. The patients were randomized and
      treated for a period of six weeks. Clinical assessments were performed by the
      general practitioner (CP) during treatment. The Sickness Impact Profile (SIP),
      the Activities of Daily Living (ADL), and a pain questionnaire were filled out by
      the patients before and after treatment. As measured with the SIP, the ADL and
      the pain questionnaire, there were no significant differences between nabumetone
      and piroxicam. The correlations between (changes in) patient assessments and
      (changes in) clinical assessments were low. The differences between the two drugs
      regarding withdrawals and adverse events were not reflected by patient health
      related quality of life assessments. There was a low correlation between patient
      health-related quality of life assessment and clinical assessments. To get a
      complete picture of the efficacy and safety of a drug, patient health-related
      quality of life assessments should be a part of a clinical trial.

PMID- 8873227
TI  - Oxidative stress in malaria; implications for prevention and therapy.
AB  - Malaria affects world-wide more than 200 million people, of which 1-2 million die
      every year. New drugs and treatment strategies are needed to face the rapidly
      increasing problems of drug resistance. During a malaria infection, both host and
      parasite are under oxidative stress. Increased production levels of reactive
      oxygen species (ROS, e.g superoxide anion and the hydroxyl radical) are produced
      by activated neutrophils in the host and during degradation of haemoglobin in the
      parasite. The effects of ROS in malaria can be both beneficial and pathological,
      depending on the amount and place of production. Enhanced ROS production after
      the administration of pro-oxidants, which is directed against the intra
      erythrocytic parasite, inhibits the infection both in vitro and in vivo. However,
      ROS are also involved in pathological changes in host tissue like damage of the
      vascular endothelial lining during a malaria infection (cerebral malaria). Pro
      oxidants support the host defense against the parasite when working in or near
      the infected cell but potentially cause vascular damage when working on or near
      the vascular lining. Examples of pro-oxidants are found among xenobiotics and
      food components. Important new drugs belonging to the class of pro-oxidants are
      artemisinin and its derivatives. Anti-oxidants potentially counteract these
      agents. Treatment with anti-oxidants or chelators of metals to prevent their
      catalytic function in the generation of ROS may prevent vascular pathology. In
      addition, the iron chelator desferrioxamine, exhibits an antiparasitic activity,
      because iron is also essential for the proliferation of the parasite. Cytokines
      play an important role in ROS-related pathology of malaria, though their
      mechanism of action is not completely elucidated. This field might bring up new
      treatment concepts and drugs. Drugs which prevent host pathology, such as the
      cerebral complications might be life saving.

PMID- 8873229
TI  - Feasibility of an antibiotic order form. First experience in the department of
      internal medicine of a university hospital.
AB  - Inadequate control of antimicrobial drug use may lead to excessive expenditure
      for antimicrobial drugs and improper prescribing it may also result in the
      emergence of multiresistant bacteria. An antibiotic order form may improve the
      quality of prescriptions by increasing the awareness of the physician of the
      antimicrobial spectrum needed (i.e. which microorganism is expected in a given
      patient), the desired duration of treatment, the potential need to adjust dosage,
      and the potential allergy of the patient to the drug. Furthermore, such an
      antibiotic order form facilitates prospective evaluation of both the quantity and
      the quality of prescribing practice. However, the introduction of yet another
      form to fill in may be met with opposition from prescribers. We have developed an
      easy-to-use antibiotic order form that incorporated the conventional medication
      order that was already in use in our hospital. Compliance (percentage of
      antimicrobial drug prescriptions for which an order form was used) was on average
      58% in the first two weeks after introduction, and remained thereafter between
      60% and 90%, varying between the different wards. Data retrieved from the
      antibiotic order forms could be used for surveillance We conclude that this
      antibiotic order form was feasible in a large department of internal medicine of
      a university hospital. Future usefulness will depend on compliance and on
      personnel support for data processing and intervention.

PMID- 8873230
TI  - Pharmaceutical analysis of the oral iron chelator deferiprone (DMHP,L1).
AB  - The oral iron chelator deferiprone (1,2-dimethyl-3-hydroxy-pyrid-4-one, DMHP, LT
      or CP20) can be a useful drug in patients with transfusional hemosiderosis. From
      1987 about 1000 patients in 16 countries have taken this drug on the base of
      clinical trials or compassionate use. Since this compound is only available as a
      raw substance, it is important to ascertain its purity before bringing the drug
      into a pharmaceutical formulation. Because deferiprone is administered
      chronically and in high doses, intake of potential toxic impurities can be
      substantial. In this article a proposal for the quality control of deferiprone is
      presented in the form of a pharmaceutical monograph. This includes the analytical
      methods required for identification, purity checking and assay. Furthermore the
      way we synthesized the drug to get hold of it in a pure form is described. This
      synthesis is also used in manufacturing the drug commercially. The monograph can
      be used as a guideline for standardization of the quality of deferiprone to be
      used for further study and treatment.

PMID- 8873231
TI  - Pentamidine aerosols and environmental contamination: health-care workers at
      risk.
AB  - In our hospital safety guidelines are available for the handling of pentamidine
      in the day-care department, but no safety ventilation cabin is used because only
      one patient a day has been treated, The number of patients to be treated,
      however, is growing, resulting in the need to treat more than one patient a day.
      To determine the environmental contamination and exposure of health-care workers
      during and after aerosolised pentamidine treatment of more than one patient with
      the acquired immunodeficiency syndrome a day a high-performance liquid
      chromatographic method is used for the detection and quantification of
      pentamidine. High volume air samples were taken before, immediately after and the
      day after a treatment session of up to three patients. Also, sediment samples and
      personal air samples close to the mouth of the health-care workers were taken.
      Immediately after a treatment session the air in the room contains 1.0-99.7
      micrograms pentamidine per m3 of air. Before and the morning after treatment no
      pentamidine could be detected in the air. Sediment samples vary in detectable
      amounts of pentamidine from < 5 to 1165 micrograms. pentamidine/cm2. The personal
      air samples also show a large variation in quantities of pentamidine: < 5-170 ng
      a filter. When large amounts of pentamidine in the high volume air samples are
      found high amounts of pentamidine on the sediment samples and the personal air
      samples are found as well. This means that the patients treated should be
      instructed well on how to use the nebulizer correctly and be monitored during
      treatment. Additional safety measures (for example the use of a safety
      ventilation cabin) should be taken when more than one patient is treated a day.

PMID- 8873232
TI  - Interaction between uterine PGE and PGF2 alpha production and the nitridergic
      system during embryonic implantation in the rat.
AB  - Embryonic implantation is a complex process in which both maternal and embryonic
      signals are involved. In the present study, we evaluated changes in uterine
      prostaglandins production and nitric oxide synthase (NOS) activity during the
      course of early pregnancy and their interaction during implantation in rats.
      Uterine phospholipase A2 (PLA2) activity is increased on days 5 (day of
      ovoimplantation) and 6, compared to preimplantation days (3 and 4). This enhanced
      activity might be responsible for the observed increase in uterine PGE and PGF2
      alpha production observed on day 5 of pregnancy, which induces endometrial
      vascular permeability and decidualization. When embryo access to the uterus is
      impaired, the increase of PG production is suppressed. During postimplantation,
      PGE levels return to preimplantation values, while PGF2 alpha decreased with
      respect to preimplantation values. Uterine NOS activity is also increased on day
      4 and reaches a maximum on day 5, with a profile similar to PGE and PGF2 alpha.
      Dexamethasone administered in vivo decreased uterine NOS activity on day 4 of
      pregnancy but not on day 5, suggesting the presence of at least two types of NOS
      enzymes in the early days of pregnancy. A competitive inhibitor of NOS, L-NAME
      (600 and 1000 microM) induced a decrease in PGE and PGF2 alpha production in
      uterine tissue on day 5 of pregnancy. These results suggest the existence of a
      physiologically relevant nitridergic system which modulates prostaglandin
      production in the rat uterus during embryonic implantation.

PMID- 8873233
TI  - Prostaglandin E2 increases the calcium concentration in rat brown adipocytes and
      their consumption of oxygen.
AB  - Effects of prostaglandin E2 (PGE2) were examined on the oxygen consumption and
      intracellular calcium concentration of rat brown adipose tissue (BAT). PGE2 0.1
      nM-1 microM increased oxygen consumption of the tissue blocks of BAT, with a
      maximum 2-13 min after PGE2 administration. PGE2 was most effective at 1 and 10
      nM, and the oxygen consumption was elevated for over 40 min. Pretreatment of BAT
      with indomethacin, a prostaglandin synthesis inhibitor, did not affect the
      increase in oxygen consumption induced by noradrenaline. PGE2 at 1-10 nM
      gradually increased the intracellular calcium concentration of freshly dispersed
      single brown adipocytes by 3-4 times in 30 min. PGF2 also increased the
      intracellular calcium concentration of brown adipocytes in calcium-free medium.
      These results raise the possibility that PGE2 and noradrenaline affect heat
      genesis and metabolism of BAT independently.

PMID- 8873234
TI  - Dose-related action of estradiol on placental prostanoid prediction.
AB  - Prostanoids play an important role throughout all of pregnancy and during the
      initiation and progress of labor. The human placenta at term produces large
      quantities of prostanoids, yet little is known of the factors that regulate their
      biosynthesis. Herein, we report the effect of estradiol or estradiol and
      progesterone on the basal release of placental prostanoids from fresh human term
      placental explants using a perifusion system. The basal release of prostaglandin
      E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), thromboxane (TxB2) and 6-keto
      prostaglandin F1 alpha (6-keto-PGF1 alpha) increased about 50% from the fifth to
      the ninth hour in culture, while the release of 13, 14-dihydro-15-keto-PGF (PGFM)
      remained constant and hCG release decreased. The dose-related effect of estradiol
      (20-2,000 ng/ml) in the perifusing medium starting at the fifth hour of
      perifusion (i.e., the zero treatment time) effected no change in the release of
      TxB2, PGF2 alpha, PGFM or hCG. A biphasic action on the release of 6-keto-PGF1
      alpha was observed, i.e. it was significantly decreased when incubated with 20
      ng/ml of estradiol, but effected an increase after exposure to 200 ng/ml. The
      concomitant addition of progesterone (2,000 ng/ml) with estradiol (200 ng/ml)
      significantly inhibited the stimulatory action of estradiol at this dose. The
      release of PGF2 was inhibited in a dose-related fashion with increasing dose of
      estradiol. The addition of progesterone with estradiol (2,000 and 200 ng/ml,
      respectively) reversed the inhibition of PGE2 by estradiol alone. These data
      demonstrate that physiologic levels of estradiol affect 6-keto-PGF1 alpha and
      PGE2 release from the human term placenta, but do not significantly alter
      production of TxB2, PGFM or hCG under these conditions.

PMID- 8873235
TI  - 5-Hydroxyeicosatetraenoic acid and human parturition.
AB  - 5-Hydroxyeicosatetraenoic acid (5-HETE) is an arachidonic acid (AA) metabolite
      derived from the lipoxygenase pathway which is capable of inducing uterine
      contractions. The purpose of this study was to determine a). whether 5-HETE
      concentrations in amniotic fluid increase before or after the onset of labor and
      b). whether acetylsalicylic acid (ASA) could modulate the production of 5-HETE by
      human amnion cells. 5-HETE concentrations are increased in amniotic fluid before
      the onset of labor. Furthermore, ASA treatment as expected inhibited PGE2, but
      also significantly increased 5-HETE production by amnion cells. 5-HETE
      concentrations on average increased by greater than 2.5 fold (p < 0.001) in
      amniotic fluid prior to spontaneous labor when compared with samples obtained
      from the same patients earlier in gestation and therefore may be important in
      mechanisms regulating the onset of labor. ASA provokes an increase in 5-HETE
      biosynthesis by amnion cells: control media 2.60 +/- 1.5, ASA treatment alone
      5.17 +/- 0.20, IL-1 beta alone 6.39 +/- 2.1, and ASA + IL-1 beta 8.95 +/- 1.2
      (mean +/- SEM) picograms per microgram protein per 16 hours. These findings may
      explain in part why cyclooxygenase inhibitors are not always successful in
      treating women with preterm labor.

PMID- 8873236
TI  - Intracellular glutathione level modulates the induction of apoptosis by delta 12
      prostaglandin J2.
AB  - We studied the effect of intracellular glutathione (GSH), which was known to
      conjugate readily with an alpha, beta-unsaturated carbonyl of 9-deoxy-delta 9,12
      13,14-dihydroPGD2 (delta 12-PGJ2), on the cytotoxicity of delta 12-PGJ2. delta 12
      PGJ2 caused DNA fragmentation in human hepatocellular carcinoma Hep 3B cells,
      which was blocked by cycloheximide (CHX). The delta 12-PGJ2-induced apoptosis was
      augmented by GSH depletion resulted from pretreatment with buthioninine
      sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase. On the
      contrary, N-acetyl-cysteine (NAC), a precursor of cysteine, elevated the GSH
      level and protected cells from initiating apoptosis by delta 12-PGJ2. Sodium
      arsenite, a thiol-reactive agent, also induced apoptosis, which was potentiated
      or attenuated by BSO or NAC treatment respectively. These results suggest that
      the apoptosis-inducing activity of delta 12-PGJ2 is due to thiol-reactivity and
      intracellular GSH modulates the delta 12-PGJ2-induced apoptosis by regulating the
      accessibility of delta 12-PGJ2 to target proteins containing thiol groups.

PMID- 8873237
TI  - Intracerebroventricular neuropeptide Y produces hyperinsulinemia in the presence
      and absence of food.
AB  - Acute administration of neuropeptide Y into the hypothalamus or cerebral
      ventricles produces hyperphagia and hyperinsulinemia. However, it is not known to
      what extent the hyperinsulinemia depends on the food intake. Consequently, serum
      insulin and glucose, as well as food and water consumption, were measured over 3
      h, following injection of 1-20 micrograms neuropeptide Y into the third ventricle
      of adult female rats. In the presence of food, 1-10 micrograms neuropeptide Y
      produced a dose-dependent increase in food and water intake and serum insulin.
      Insulin levels were closely correlated with the quantity of food ingested. In the
      absence of food, 1-20 micrograms neuropeptide Y produced a dose-dependent
      increase in water intake, whereas 1-5 micrograms produced a does-dependent
      increase in serum insulin. We concluded that ICV neuropeptide Y can stimulate
      insulin secretion even at low doses and this response does not completely depend
      on food intake.

PMID- 8873238
TI  - Castration affects the emission of an ultrasonic vocalization in a nocturnal
      primate, the grey mouse lemur (Microcebus murinus).
AB  - Male primates have evolved particular displays to advertise male fitness. In
      nocturnal prosimians it was assumed that such displays (vocal advertisement,
      marking behaviour) are hormonally dependent and influenced by olfactory cues of a
      receptive female. To test this assumption mouse lemur males of different gonadal
      status (males castrated as adults, normal males), or of varying olfactory input
      (males vomeronasalectomized or bulbectomized as adults) were paired with intact
      "stimulus" preoestrous females and vocalization, vocal rates, and marking
      behaviours were monitored. The vocal rate of only one particular vocalization,
      the "trill" advertisement call, was sexually dimorphic and changed depending on
      gonadal status. Vocalization rate declined significantly in sexually experienced,
      castrated males as did their marking behaviour. There was however no significant
      correlation between either calling rate or marking behaviour and plasma
      testosterone levels in gonadally intact males. Neither vomeronasalectomy nor
      bulbectomy had a significant effect on trill calling rate or marking behaviour.
      Results imply that testicular hormones have a greater impact on advertisement
      calling and marking motivation than olfactory information of preoestrous females.
      In contrast to rodents, ultrasonic calling rate seems to be not only dependent on
      gonadal status, but also on social experience.

PMID- 8873239
TI  - Increased open field locomotion and decreased striatal GABAA binding after
      activity wheel running.
AB  - Open-field behavior has been used to model reductions in anxiety-related
      behaviors in the rat after chronic physical activity. Plausible mechanisms for
      the increased open field locomotion observed after physical activity have not
      been studied. Open field locomotion is decreased by gamma-aminobutyric acid
      (GABA) and its agonists, and increased by GABA antagonists, in the ventral
      striatum. Hence, we tested the hypothesis that increased open field locomotion
      following chronic physical activity would be accompanied by a decrease in the
      number of GABAA receptors in the corpus striatum. Young (approximately 55 days)
      male Sprague-Dawley rats (N = 24) were randomly assigned to three conditions: 24
      h access to an activity wheel (AW), running for 1 h without shock 6 days/week on
      a motorized treadmill (TM), or sedentary control (C). Open field locomotion
      (total and center squares traversed), defecation, and urination were assessed on
      each of 3 consecutive days prior to and again after 8 weeks of physical activity.
      Open field locomotion (total and center squares) increased after activity wheel
      running, decreased after treadmill training, and did not change for control
      animals. GABAA receptor density indicated by [3H] bicuculline binding (fmol/mg)
      was lower for activity wheel animals compared with treadmill animals and
      controls. GABA concentration (mumol/g) was not different between activity wheel
      and treadmill groups but was higher for both groups contrasted with controls. Our
      findings of decreased GABAA density in the corpus striatum concomitant with an
      increase in open field locomotion are consistent with an anxiolytic effect of
      chronic activity wheel running.

PMID- 8873240
TI  - Peripheral administration of a corticotropin-releasing factor antagonist
      increases the vocalizing and locomotor activity of isolated guinea pig pups.
AB  - Guinea pig pups vocalized more and were more active during a 60-min period of
      isolation in a novel environment when injected SC with 50 micrograms of the
      corticotropin-releasing factor (CRF) antagonist, [D-Phe]CRF12-41, than when
      injected with saline vehicle only. More pups exhibited eye closing and extensive
      piloerection when injected with saline than when injected with the antagonist.
      Plasma levels of cortisol following testing were not affected by the injections.
      These results support the hypothesis that endogenous CRF contributes to the
      normal decline in vocalizing and locomotor activity that guinea pig pups show
      with continued isolation. The results also suggest that endogenous CRF plays a
      role in the eye closing and piloerection of isolated pups. The finding that the
      dose of the antagonist used altered behavior, yet was not sufficient to lower
      plasma cortisol levels, supports earlier evidence that the observed effects of
      CRF are not due to the actions of ACTH or glucocorticoids.

PMID- 8873241
TI  - Flavor-postingestive consequence associations incorporate the behaviorally
      opposing effects of positive reinforcement and anticipated satiety: implications
      for interpreting two-bottle tests.
AB  - Rats consuming distinctively flavored solutions containing different numbers of
      calories learn to associate each flavor with the ensuing postingestive effects
      ("flavor-postingestive consequence learning"). The hallmark of such learning is
      preferential consumption of one of the flavors in two-bottle tests (both flavors
      presented in nutrient-identical solutions). Two experiments were conducted to
      characterize the relationship between the number of calories associated with
      flavors and subsequent preferences in two-bottle tests. In Experiment 1, three
      groups of rats each associated distinctive flavors with real-fed sugar and with
      sham-fed sugar. The groups differed in the concentration of sucrose (8%, 14%,
      24%) with which they were trained. In two-bottle tests rats trained with 8%
      sucrose preferred the real-fed flavor, whereas rats trained with 24% sucrose
      preferred the sham-fed flavor. Rats trained with 14% sucrose were intermediate to
      the other groups. In Experiment 2, two groups of rats associated distinctive
      flavors with two concentrations of real-fed sucrose. In two-bottle tests, the
      group trained with 1% and 5% sucrose preferred the flavor paired with the higher
      concentration, whereas the group trained with 5% and 30% sucrose preferred the
      flavor paired with the lower concentration. These findings suggest that flavor
      postingestive consequence learning incorporates both positive reinforcement,
      which has the behavioral effect of increasing intake of the associated flavor,
      and anticipated satiety, which has the behavioral effect of suppressing intake of
      the associated flavor. When a flavor is associated with relatively few calories,
      the positive reinforcing effect predominates over anticipated satiety. However,
      when a flavor is associated with a greater number of calories, anticipated
      satiety predominates over the positive reinforcing effect.

PMID- 8873242
TI  - Intraventricular neuropeptide Y does not stimulate food intake in the baboon.
AB  - In the present study, we examined the ability of the orexigenic peptide
      neuropeptide Y (NPY) to stimulate feeding when administered into the lateral
      ventricle of baboons. No increase of either meal size or total daily food intake
      was observed over the dose range tested (1-30 micrograms). These results suggest
      that, in the baboon, NPY may not be an orexigen as it is in other species.

PMID- 8873243
TI  - Failure to induce defecation in rats exposed to fixed-time schedules of liquid
      food delivery.
AB  - Previous studies have found that defecation increases in rats exposed to fixed
      time schedules of dry food delivery. The purpose of the present study was to
      examine whether increases in defecation could be induced in rats exposed to fixed
      time schedules of liquid food delivery. Eight rats were exposed to fixed-time 30
      , 60-, and 120-s schedules of liquid food delivery. None of the subjects excreted
      significantly more fecal boli under the fixed-time schedules than during massed
      food control sessions in which an equivalent amount of food was presented at the
      beginning of the sessions. Thus, the present findings identify a previously
      unknown constraint on schedule-induced defecation in rats.

PMID- 8873244
TI  - The specific locus and time course of the body protein adjustments produced in
      rats by lesions of the lateral hypothalamus.
AB  - Lesions of the lateral hypothalamus (LH) result in a body weight reduction
      characterized by declines in both lean and adipose tissues. The body fat of LH
      lesioned rats can be restored to or above the levels of nonlesioned rats by
      overfeeding. However, the protein deficit cannot be so reversed, suggesting that
      the lesion-induced body protein reduction is chronic. To ascertain which specific
      tissues surrender protein following LH lesions, the present studies measured
      skeletal muscle and visceral organ weights at 2 weeks and 6 months postlesion.
      Daily protein losses during the first 2 weeks postlesion were also assessed to
      determine the temporal pattern of whole-body protein adjustments. The results at
      6 months postlesion suggest that LH lesions lead to reductions in the maintained
      mass of all protein-based tissues. The largest absolute loss was from skeletal
      muscle, whereas liver sustained the greatest proportional loss. Assessment of
      daily postlesion protein balance indicate that the majority of body protein
      losses occurred during the initial 6 days postlesion. Skeletal muscle mass was
      characterized by large losses at 2 weeks, and proportionally smaller losses at 6
      months. Reductions of visceral organ mass were marginal at 2 weeks, but
      substantial by 6 months postlesion. Thus, whereas all protein-based tissues are
      reduced by LH lesions, the protein content of specific tissues appears to be
      altered differentially. Major reductions in total body protein occur in the first
      2 weeks of the LH syndrome, with an apparent redistribution of protein later.
      This redistribution results in the partial restoration of skeletal muscle at the
      expense of existing visceral organ protein or its subsequent accretion.

PMID- 8873245
TI  - Enhanced water intake after asymmetric hindbrain lesions.
AB  - Previous reports indicate rats with lesions of the lateral parabrachial nucleus
      (IPBN) or lesions of the area postrema (AP) and adjacent nucleus of the solitary
      tract (NTS) consume abnormally large amounts of water after treatment with SC
      isoproterenol (ISOP) or angiotensin II. In the present study, we found that IPBN
      bilateral lesions resulted in increased water intake after ISOP treatment as
      noted previously. We also found that rats with ibotenic acid lesions of the left
      IPBN and a knife cut on the right side of the AP drank an abnormally large amount
      of water after treatment with ISOP. Interestingly, rats with lesions of the right
      IPBN and a knife cut on the left side of the AP did not show the enhanced
      drinking behavior. Rats with AP and adjacent NTS lesions had an increased sodium
      appetite, but water intake after ISOP treatment was not enhanced. Bilateral IPBN
      lesions and asymmetric lesions of the AP and IPBN did not result in enhanced
      sodium appetite. These data suggest that a pathway from the AP/mNTS to the 1PBN
      is important in the regulation of fluid balance.

PMID- 8873246
TI  - Social behaviour in sheep relates to behaviour and neurotransmitter responses to
      nociceptive stimuli.
AB  - Sheep in the field display differences in social behaviour. These differences
      allow a division into three social groups with distinct behavioural occurrences
      and frequencies. The behavioural and neurotransmission responses of each of these
      groups to aversive stimuli were compared. Behavioural responses were seen to both
      forelimb electric shocks and thermal heating of the nose in all groups. These
      responses changed with stimulus repetition in a group-dependent manner.
      Microdialysis probe studies of neurotransmitter release in the somatosensory
      cortex indicated neurotransmitter responses to stimuli in all animals that varied
      with both animal group and stimulus repetition. Group 1 animals, aggressive and
      socially active, showed increases in gamma amino-4-butyric acid (GABA) with
      initial stimulus presentation; this increased with stimulus repetition.
      Behavioural responses to the stimuli decreased with repetition and nonstimulus
      related behaviours, during the course of the experiment, increased. Both of these
      appeared dependent upon GABA. Group 2 animals, moderately aggressive and socially
      active, released opioid-like peptides (OLP) upon initial exposure to stimuli but,
      with repetition, switched to using GABA. Group 3 animals, nonaggressive and
      socially inactive, released OLP with initial and repeat stimuli. In groups 2 and
      3, both GABA and OLP appear to reduce stimulus-related behaviour, but OLP
      appeared to also reduce nonstimulus-related behaviour and GABA increased these.
      Changes were independent of animal liveweight. Glutamate was released in response
      to stimuli in all 3 groups and, with repetition, fell in groups 1 and 2 but
      increased in group 3. An animal's social behaviour and status may predict its
      response to a stimulus.

PMID- 8873247
TI  - Lateralization of pectoral stridulation sound production in the channel catfish.
AB  - Sounds of the channel catfish Ictalurus punctatus were found to consist of a
      rapid series of pulses produced by rubbing a ridged process on the first pectoral
      spine against the rough surface of a groove in the pectoral girdle during fin
      abduction. Although sounds can be made with either fin, approximately half of the
      individuals exhibited a fin preference, and 90% of these preferred the right fin.
      Unlike examples of handedness in other invertebrates and fishes, this preference
      is not simply a matter of anatomical asymmetry, but as in humans, reflects a
      preference between two equally developed limbs.

PMID- 8873248
TI  - Comparison of the renal effects of six sedating agents in rats.
AB  - This study was designed to compare the renal effects of sedation with alphaxalone
      alphadolone, etomidate, propofol, midazolam, fentanyl-fluanisone, and thiopental
      in rats. The sedative dose was defined as the highest dose that abolished the
      escape response without affecting the righting reflex. Female Wistar rats were
      chronically catheterized with a jugular vein catheter, and urine flow rate and
      renal clearances of inulin (glomerular filtration rate = GFR), sodium, and
      lithium (used as an index of proximal tubular function) were measured in the
      conscious, unrestrained state (n = 107 experiments). In a separate series (n = 70
      experiments), the effect of sedative doses of each drug on the nociceptive
      threshold was tested with the tail-flick test. Responses in sedated animals were
      compared to responses in animals infused with the vehicle. Fentanyl-fluanisone
      and thiopental had hypoalgesic actions in sedating doses. Propofol, fentanyl
      fluanisone, and thiopental reduced GFR by 20-30%. Urine flow rate was
      significantly decreased by propofol (-24%) and thiopental (-48%). Propofol and
      fentanyl-fluanisone reduced fractional lithium excretion by 9-13%. Only
      alphaxalone-alphadolone, etomidate, and midazolam produced sedation without
      affecting renal function in rats. Because midazolam produced the most consistent
      degree of sedation, we conclude that midazolam is the least confounding sedative
      agent for renal function studies in conscious rats.

PMID- 8873250
TI  - Circadian rhythms of locomotor activity in the goldfish Carassius auratus.
AB  - Locomotor activities in the goldfish Carassius auratus were recorded under light
      dark (LD) and constant light regimens. Under LD 12:12, all goldfish adjusted to
      given LD cycles. Activity patterns were classified into three types: L-type
      activity during the photophase (83%), LD-type activity both during the photophase
      and the scotophase (10%), and D-type activity during the scotophase (7%).
      However, these patterns were not fixed, but flexible. Under constant conditions,
      goldfish exhibited circadian locomotor activities: The proportions of appearance
      of circadian rhythms and tau values under constant darkness (DD), constant light
      (LL, 500 lx) and constant dim light (dimLL, 20 lx) were 57% (24.4 +/- 1.6 h,
      [mean +/- SE], n = 34), 57% (25.2 +/- 2.5 h, n = 35) and 67% (26.0 +/- 3.4 h, n =
      10), respectively. These results indicate that the goldfish exhibit flexibility
      in phasing of locomotor activity rhythms under LD 12:12. In addition, the
      coupling between circadian clocks and locomotor activities does not seem strong,
      although the diel locomotor activity in the goldfish is regulated, in part, by a
      circadian clock. These results are discussed in context with the structure of the
      teleostean circadian system.

PMID- 8873249
TI  - Effects of daily injections of melatonin on locomotor activity rhythms in rats
      maintained under constant bright or dim light.
AB  - It has been demonstrated that daily melatonin injections entrain free-running
      locomotor activity rhythms in rats kept in constant darkness, and synchronize
      disrupted circadian patterns of wheel-running activity under constant light.
      Contrary to these previous observations, our result did not show that daily
      injections of melatonin synchronize disrupted locomotor activity in rats
      maintained under constant bright light. On the other hand, daily treatment with
      melatonin entrained the intact free-running rhythm in rats kept in constant dim
      light. This entrainment took place only when the time of injection corresponded
      to the activity onset time, and similar results were obtained in blinded rats.
      Pinealectomy had no influences on either the free-running rhythm or melatonin
      induced entrainment. To examine whether a behavioral feedback mechanism is
      involved in melatonin-induced entrainment, rats were immobilized for 3 h after
      each daily melatonin injections. This did not interfere with melatonin-induced
      entrainment. These results suggest that the mechanism underlying melatonin
      induced entrainment of activity rhythms may be different from those in photic and
      behavioral entrainment.

PMID- 8873251
TI  - Inhibition of male sex behavior by androgen receptor blockade in preoptic area or
      hypothalamus, but not amygdala or septum.
AB  - Inhibition of masculine copulatory behavior was previously demonstrated following
      systemic injections of hydroxyflutamide (OHF). In the present study, we examined
      the localization of the effects of this androgen receptor blocker by direct
      intracranial implantation of OHF into the medial preoptic area (MPOA),
      ventromedial nucleus of hypothalamus (VMN), medial amygdala (AME), and lateral
      septum (SEPT). Animals were implanted intracranially with crystalline OHF or
      cholesterol, and at the same time received two 10-mm testosterone-filled Silastic
      capsules SC. Tests for restoration of copulatory behavior were initiated 3 days
      later, and conducted twice weekly for 2 weeks. Implants of OHF into the MPOA were
      effective in preventing restoration of male sexual behavior. However, the most
      effective site was the VMN. Implants of OHF into the AME were only partially
      effective in stimulating male sexual behavior, whereas implants into the SEPT had
      no effect. The OHF was discontinued and 1 week later males were retested for
      sexual behavior. The majority of these animals ejaculated, indicating, that the
      effects of OHF are reversible. The result of this study demonstrate that the
      functional integrity of androgen receptors in some, but not all, androgen
      concentrating brain loci is necessary for the expression of the complete pattern
      of male sexual behavior. These data lend support to the view that androgen
      receptor populations in specific brain loci differentially express proteins
      involved in mediating the masculine copulatory response.

PMID- 8873252
TI  - Food intake and body weight in rats with daily food-availability restrictions.
AB  - Male Wistar rats were offered food for either 24, 6, or 1 h a day at two
      different ambient temperatures -21 or 6 degrees C. At room temperature, rats
      offered food for 6 h a day matched their food intake to that of rats with 24 h of
      food-availability in 2-3 days, so that no main changes in total food intake,
      gross food efficiency, and body weight were recorded. No impairment of
      thermoregulatory capacity was recorded as judged by the unaltered oxidative
      capacity of brown adipose tissue and skeletal muscle. Nonetheless, a transient
      hypothermia was recorded at the beginning of the experiment in the food
      restricted group. Rats that were only offered food 1 h a day were unable to
      sustain the food intake of the control animals, so that a continuous decline in
      body weight and a negative gross food efficiency ensured. In the cold, the food
      intake of rats offered food for only 6 or 1 h a day was similar to that showed by
      the corresponding groups at 21 degrees C. These results suggest a maximum rate
      for digestive processes, irrespective of ambient temperature. However, such
      levels of food intake were clearly insufficient to cope with the thermoregulatory
      enhanced energy demand at 6 degrees C, ad judged by the decrease in body weight.

PMID- 8873253
TI  - Corticosterone is involved in foot shock-induced inactivity in rats.
AB  - Inescapable shock (IS) exposure induces behavioral inactivity, related to
      behavioral alterations in subsequent tests (i.e., escape failure, and inactivity
      during shuttle box task). Metyrapone (150 mg/kg, IP), a corticosterone (CS)
      synthesis inhibitor, administered 3 h prior to IS reduced inactivity during this
      aversive experience. Forty-eight hours later, when these rats were submitted to a
      shuttle box task, a reduction in both escape failure and inactivity was observed.
      These effects were reversed by CS (20 mg/kg, SC) and dose dependent of the
      synthetic glucocorticoid dexamethasone, both administered 1 h before IS. When
      metyrapone was administered 3 h before the shuttle box task to IS-exposed
      animals, escape failures and inactivity were markedly reduced. This effect was
      subsequently reversed by CS. The dynamics of changes in serum CS concentrations
      after both IS and shuttle box task paralleled behavioral changes. Animals
      injected with metyrapone before IS, which displayed active behavior, showed serum
      CS levels stable at their basal levels after shock, and their secretion pattern
      was quite attenuated after the shuttle box task, whereas vehicle-, CS alone-, and
      metyrapone + CS-injected animals showed higher serum CS concentrations post-IS,
      which slowly decreased to their corresponding basal levels. CS secretion after
      the shuttle box task was similar for the three groups: it had the same magnitude
      as after IS, though the decrease was faster. In all groups, animals displayed
      passive behavior. These results indicate that glucocorticoids are involved in the
      onset and expression of passive behaviors induced by uncontrollable stressors.
      Therefore, it is possible to suggest a functional relationship between CS
      released by exposure to inescapable stressor and the behavioral strategies
      adopted by rats under this stressful condition.

PMID- 8873254
TI  - Penile erection in response to remote cues from females: albino rats severely
      impaired relative to pigmented strains.
AB  - Male rats have been observed to display erections when exposed to inaccessible
      estrous females, and it was suggested that these "noncontact erections" (NCEs)
      represent a species-typical response that may index sexual arousal. Initial
      efforts in other laboratories to repeat and extend this research were
      unsuccessful, and it appeared that differences in the rat strains being used
      might be responsible. To address this question NCE tests were given to rats of
      two albino strains, Wistar and Sprague-Dawley, and two pigmented strains, hooded
      Long-Evans and inbred Brown Norway. A high proportion of Long-Evans and Brown
      Norway rats displayed NCEs, whereas Wistar and Sprague-Dawley albino rats rarely
      did. Additional experiments did not reveal the reasons for the strain difference
      in NCE, but they provided evidence against hypotheses based on the relative
      erectogenic effect of albino and hooded estrous females, the attention paid to
      estrous females, the motor repertoire, or erectile function per se. Albinism
      related neural pathology, possibly outside of the visual system, may contribute
      to the deficit in NCE in albino rats.

PMID- 8873255
TI  - Clinico-ECoG correlate of megimide-induced epileptic seizures in epilepsy-prone
      El and its mother strain nonepileptic ddY mice.
AB  - Megimide-induced epileptic seizures were recorded in nine male El and six male
      ddY mice with the chronic implantation technique for monopolar recording of
      electrocorticogram (ECoG). ECoG were recorded from preictal period until 30 min
      after general tonic clonic convulsion (GTC). In total, 14 GTC in ddY and 15 in El
      were recorded. There were three periods as for clinico-ECoG correlate in both
      strains: a twitching period, GTC, and a postictal period. The GTC had three
      phases: a tonic phase, a tonic phase with clonic movements, and a clonic phase.
      Twitching movements (twitching period) consisted of rapid backward jerks of the
      neck, associated with different electrocortical phenotypes: focal spikes,
      generalized spikes, or generalized spike and wave complex. During tonic phase of
      GTC, clonic movement of the limbs was the most frequently observed clinical
      phenotype, whereas twitchings were the predominant manifestation during clonic
      phase of GTC in both strains. The ictal ECoG phenotype was strain specific:
      generalized spikes predominated in ddY and occipital spikes in El mice. There
      were postictal spikes without specificity for localization in both strains.

PMID- 8873256
TI  - Ever higher: constant rise of body weight set-point in growing zucker rats.
AB  - The mass of food hoarded by rats given access to food only 2 h per day is
      proportional to the rats' body weight deficit. The intersect of the regression
      line of hoarded food plotted against body weight gives an indication of the body
      weight set-point. In the present work, the hoarding behavior of six obese and six
      control rats was measured every day at various body weights from 8 to 24 weeks of
      age. Every other week the animals were anesthetized and their percentage of fat
      was measured in vivo with a total body electrical conductivity method (TOBEC).
      Lean mass and body length of the obese, and their controls, increased similarly
      in both groups over the period of the measurements. On the other hand, the body
      weights increased more in obese, from 174 +/- 5 to 729 +/- 18 g (n = 6), than in
      controls, from 157 +/- 5 g to 452 +/- 14 g (n = 6). The body weight set-point,
      calculated every other week for both groups of rats, increased progressively with
      age. At the age of 24 weeks, the mean set-point for body weight regulation was
      758 +/- 13 g in obese and 467 +/- 12 g in controls. This result suggests that the
      obese fa/fa rat defends its fat content, or a variable correlated to the fat
      content.

PMID- 8873257
TI  - Enforced water drinking induces changes in burying behavior and social
      interaction test in rats.
AB  - The effect of water deprivation and water intake on experimental anxiety in rats
      was tested using burying behavior (BB) and social interaction (SI) anxiety
      paradigms. Two groups of animals were studied: a control group with free access
      to water, and a 72-h water-deprived experimental group. Anxiety was studied in a
      water-deprived group or following a 10-min period of ad lib water drinking. An
      increase in the mean time of defensive burying in animals deprived for 72 h was
      observed, whereas an important reduction occurred in the levels of burying
      behavior immediately after the animals were allowed to drink ad lib for 10 min.
      These results suggest that the observed increase in defensive burying in the
      water-deprived animals represents an anxiogenic effect, whereas the decrease in
      this behavior in water-satiated animals is considered an anxiolytic action. The
      temporal course of reduction in burying behavior, observed after water drinking,
      revealed that the anxiolytic action lasts 5 min, whereas 15-30 min after
      drinking, burying behavior levels were similar to those in the control group. In
      the social interaction experiment a partial anxiogenic/anxiolytic effect of water
      deprivation and water intake was observed. The adaptive meaning of anxiogenic and
      anxiolytic changes linked to consummatory behaviors in rats is discussed on the
      basis of behavioral and biochemical data.

PMID- 8873258
TI  - Effects of estradiol on sexual receptivity, wheel-running behavior, and vaginal
      estrus in virgin prairie voles.
AB  - This study examined the effects of estradiol on sexual receptivity and vaginal
      estrus in experienced and virgin female prairie voles, and running wheel activity
      in virgin females. Because prairie voles undergo induced ovulation, we predicted
      that exogenous estradiol would not affect activity patterns nor stimulate
      lordosis in virgins. Females were SC injected with estradiol benzoate (ED) and
      placed with males, and sexual receptivity was monitored. In experienced females
      0.5 micrograms of EB resulted in 100% of the females displaying lordosis after 48
      h. In contrast, only 20% of the females receiving 0.05 micrograms displayed
      lordosis. Less than 20% of virgin females receiving EB displayed lordosis.
      Virgins displayed no change in wheel-running activity after EB treatments,
      indicating that behaviors that are influenced by estradiol and regulated by the
      brain may require previous exposure to males to develop. Although all females
      receiving the 0.5 micrograms of EB displayed vaginal estrus, virgin females
      achieved vaginal estrus later than experienced females, suggesting that exposure
      to males has a priming effect resulting in a reduced period to vaginal estrus.

PMID- 8873259
TI  - Reductions in locomotor activity following central opioid receptor subtype
      antagonists in rats.
AB  - Opioid agonists produce biphasic (decreases then increases) effects upon activity
      in rats. General opioid antagonists typically suppress activity. Selective opioid
      antagonists reduce weight and food intake. However, the latter effects cannot
      fully account for the former effects. To assess the possibility that selective
      opioid antagonists might decrease weight by increasing activity, the present
      study examined whether central administration of either mu (beta-funaltrexamine:
      20 micrograms), mu1 (naloxonazine: 50 micrograms), delta1 ([D
      Ala2,Leu5,Cys6]enkephalin: 40 micrograms), delta2 (naltrindole isothiocyanate: 20
      micrograms), or kappa1 (nor-binaltorphamine: 20 micrograms) opioid antagonists
      altered total, ambulatory, or stereotypic activity. Each of the antagonists
      significantly reduced total (mu: 18%, mu1: 31%, delta1: 42%, delta2: 37%, kappa1:
      31%), ambulatory (mu: 17%, mu1: 27%, delta1: 34%, delta2: 37%, kappa1: 31%), and
      stereotypic (mu: 19%, mu1: 34%, delta1: 49%, delta2: 37%, kappa1: 31%) activity
      on the first day. All three activity measures were reduced by delta1 and delta2
      antagonism on the second day, whereas mu antagonism reduced total and stereotypic
      activity on the second day. The activity reductions induced by selective opioid
      receptor subtype antagonists parallel effects induced by general opioid
      antagonism, and suggest that antagonist-induced weight loss effects independent
      of intake reductions are not due to antagonist-induced hyperactivity.

PMID- 8873260
TI  - Food deprivation and the facilitatory effects of estrogen in female hamsters: the
      LH surge and locomotor activity.
AB  - Two experiments investigated short-term food deprivation effects on
      neuroendocrine processes influenced by estrogen. These studies were prompted by
      prior work indicating that food deprivation increased the number of
      immunocytochemically identified cells containing estradiol receptors in the
      medial preoptic area of ovariectomized female hamsters. Presumably, this is one
      way that changes in metabolic fuel availability might alter the responsiveness of
      one or more systems to estradiol. The purpose of this study was to investigate
      two effects of estradiol that might be affected by food deprivation; these were
      1) the positive feedback effects of estradiol on the luteinizing hormone (LH)
      surge, and 2) the facilitating effects of estradiol on locomotor activity. In
      Experiment 1, ovariectomized hamsters were administered estradiol, before or
      after 48 h of food deprivation. Two days after hormone treatment, blood was
      obtained by cardiac puncture, once in the morning (1100 h) and twice during the
      afternoon (1600-1800 h). These times were chosen to best characterize the
      magnitude of the LH surge. Food deprivation enhanced the amplitude of the LH
      surge in response to estradiol when this treatment preceded, but not when it
      followed, the administration of estradiol. However, there was variability in the
      dose of estradiol at which this effect of food deprivation occurred. In
      Experiment 2, the locomotor (running wheel) activity of two groups of gonadally
      intact female hamsters was quantified; one group was tested during the early
      (days 1 + 2; low estradiol) part of the estrous cycle, and the other group was
      tested during the late (days 3 + 4; high estradiol part of the estrous cycle. In
      both groups, testing was performed first under ad lib feeding conditions and
      again during 48 h of food deprivation. On average, the days 3 + 4 group was more
      active than the days 1 + 2 group, reflecting their differing levels of endogenous
      estradiol. Food deprivation significantly increased locomotor activity,
      independently of the stage of the estrous cycle during which it was imposed.
      These results are discussed in terms of the influence that altered estradiol
      receptor expression in the medial preoptic area might play in generating the
      effects we observed following short-term food deprivation.

PMID- 8873261
TI  - Lateral and medial septal lesions reduce anxiety in the plus-maze and probe
      burying tests.
AB  - Previous studies have shown that septal lesions produce anxiolytic-like effects
      in rat models of "anxiety" (i.e., septal lesions, like anxiolytic drugs, increase
      rats' open-arm exploration in the elevated plus-maze test and decrease rats'
      burying behavior in the shock-probe burying test). Although these anxiolytic
      effects occur after lesions to posterior (but not anterior) regions of the
      septum, their anatomical specificity has not been clearly defined with respect to
      classical subdivisions of the septum, such as the medial and lateral nuclei.
      Thus, in Experiment 1, we compared the effects of lateral or medial septal
      lesions on rats' anxiety reactions in the elevated plus-maze and shock-probe
      burying tests. Contrary to the "anxiogenic" effects of septal lesions recently
      found in a "conflict" model of anxiety, we found that both lateral and medial
      septal lesions produced equivalent anxiolytic effects in the plus-maze and shock
      probe tests. In Experiment 2, we found similar anxiolytic effects whenever
      lesions included septal areas just anterior to the fornix (i.e., the lateral
      septum) but not when septal lesions were restricted to areas just posterior to
      the fornix (i.e., the septofimbrial and triangular septal nuclei). Taken together
      with our previous results, these data suggest that classical subdivisions of the
      septum bounded rostrally by the genu of the corpus callosum and caudally by the
      fornix play an exclusively excitatory role in the control of anxiety, as
      expressed in the plus-maze and shock-probe burying models.

PMID- 8873262
TI  - Nutritional status influences the insulin response produced by acute hepatic
      vagotomy.
AB  - It has been established that the liver, through the afferent pathway of the vagus
      nerve, can influence insulin secretion. The purpose of the present study was to
      determine if this influence can be altered by different nutritional status aimed
      at inducing metabolic changes in the liver. This was carried out by comparing the
      insulin response 30 min after sectioning of the hepatic vagus branch in five
      experimental conditions: a normal (NCD) and a medium-fat (MFD) for 3 weeks, both
      with and without an overnight fast, and after an overloading liver glycogen
      protocol (normal diet). All experiments were conducted using anesthetized,
      adrenodemedullated rats. Blood was collected before and after (30 min) the
      hepatic vagotomy (HV) or a sham operation (SHM). As expected, liver glycogen
      levels were significantly (p < 0.01) lower in the fasted than in the fed
      condition, and were approximately 50% higher (p < 0.01) in the overloaded than in
      the normally fed condition. Basal insulin concentrations were also lower (p <
      0.01) in the fasted compared to the fed groups, but were significantly (p < 0.01)
      increased by the medium-fat diet. Plasma glucose levels were significantly (p <
      0.01) decreased by the overnight fast, but were not affected by the hepatic
      vagotomy. Plasma catecholamine concentrations were similar in all experimental
      conditions. Insulin concentrations were significantly (p < 0.05) increased by the
      HV, compared to SHM rats, in all experimental conditions (from 50% to 75%). The
      extent of this response was altered by the diet manipulations as the HV-induced
      insulin increase was greater (p < 0.01) in the MFD than in the NCD groups,
      whether fed or fasted. Furthermore, and contrary to our expectations, high
      hepatic glycogen contents did not reduce the insulin response to an acute hepatic
      vagotomy. These results indicate that the insulin increase induced by an acute HV
      is influenced by the prevailing metabolic conditions, and suggest that the
      hepatic vagus nerve exerts a constant inhibition on insulin secretion,
      independently of the hepatic glycogen content.

PMID- 8873263
TI  - Centrally mediated vasodilation of the rat's tail by angiotensin II.
AB  - Acute peripheral administration of angiotensin II (AngII) to rats vasodilates the
      tail and reduces both metabolic rate and body temperature. To assess the role of
      the brain in these responses to AngII, a discrete lesion was aimed at the
      subfornical organ (SFO). Such lesions are known to abolish drinking and other
      responses to circulating AngII. A control group was sham-operated. Following
      recovery from surgery, dipsogenic responses to administration of AngII (150
      micrograms/kg, SC) were tested. All lesioned rats failed to drink. One week
      later, the changes in colonic (TC) and tail skin (TSK) temperatures were measured
      following an identical injection of AngII. As reported before, control rats
      showed a substantial rise in in TSK (maximum rise 2.5 degrees C after 12 min). In
      contrast, the lesioned rats showed very little rise (0.3 degrees C) in TSK,
      significantly less than controls. The maximal drop in TC of the control group was
      slightly more (0.3 degrees C) than that of the lesioned group (0.2 degrees C),
      but the difference was not significant. The rats were, next, acutely exposed to
      cold (5 degrees C). Control rats showed a significantly larger decrease in TSK
      than lesioned rats. Lesions were verified both anatomically and using the
      functional metric of AngII-induced Fos-like immunoreactivity (Fos-IR). AngII
      induced strong Fos-IR in the SFO, median preoptic nucleus (MnPO), and in the
      magnocellular hypothalamic regions of control rats. The lesions ablated the
      anterior part of the SFO and dorsal MnPO, and greatly attenuated AngII-induced
      Fos-IR in the magnocellular hypothalamic regions. Thus, there appears to be
      central (SFO/MnPO) mediation of both the increase in TSK following administration
      of AngII and the decrease in TSK in the cold.

PMID- 8873264
TI  - A key by which the toad's visual system gets access to the domain of prey.
AB  - Searching for principles that allow toads to distinguish between prey and
      nonprey, we wondered how the toad's prey-catching activity measured as R differs
      in response to changes in significant configurational stimulus features.
      Elongated shapes moving worm-like in the direction of their longer axes are
      preferred prey dummies; but a toad is not a worm detector, and a worm is not the
      unique prey-catching releaser. Considering the frequency distributions of R
      values, we show that the release of prey catching is in a specific manner
      sensitive to the relation between the extensions of an object parallel (xl1) and
      perpendicular (xl2) to its direction of movement. It is the xl1 and xl2 features
      relating algorithm that provides the key (instruction) by which the toad's visual
      system gets access to the domain of potential prey in terms of configurational
      cues. This, within behaviorally relevant limits, largely invariant algorithm also
      holds for segmented stimuli. Further investigations show that this principle of
      object discrimination is not due to experimental procedures but emerges as a
      species-common property, of which different toad species take advantage in a
      species-specific manner. Neurobiological correlates are discussed.

PMID- 8873265
TI  - Central beta-adrenoceptor involvement in neural control of blood glucose in
      pigeons.
AB  - The effects of ICV injections of adrenaline (30 nmol in 1 microL of saline) on
      blood glucose levels were investigated in conscious adult pigeons. This procedure
      increased blood glucose levels at 15-45 min after treatment. Previous ICV
      injection of propranolol (50 nmol) suppressed the increase observed at 15 min.
      The higher propranolol dose (100 nmol) was more effective than the lower dose (50
      nmol) at blocking adrenaline-induced hyperglycemia. On the other hand, the ICV
      pretreatment with an alpha-adrenergic antagonist, phentolamine, slightly
      potentiated the hyperglycemia caused by ICV injection of adrenaline. The IP
      administration of propranolol (100 nmol) or phentolamine (100 nmol) before
      adrenaline ICV failed to induce change in the hyperglycemic response induced by
      this catecholamine. Both IP and ICV injections of these adrenergic blockers,
      before ICV injections of saline, evoked no changes in baseline glycemic levels.
      Therefore, elevation of blood glucose concentration by ICV adrenaline and
      blockade of the response by propranolol suggest the involvement of a central beta
      adrenergic mechanism in the neural control of glycemia in pigeons.

PMID- 8873266
TI  - Septal lesions impair rats' Morris test performance but facilitate left-right
      response differentiation.
AB  - Lesions in the septum impaired performance on the Morris test, a task in which
      the rat locates a hidden escape platform by use of fixed landmarks, but
      facilitated a water maze-based left-right response differentiation, a task in
      which the rat finds a hidden escape ramp by means of its internal sense of
      direction. These results are interpreted as supporting an allocentric/egocentric
      dichotomy with respect to navigation, and support the notion that rats approach
      spatial problems with a hierarchy of potential solutions in which allocentric
      solutions take precedence over egocentric ones. The septal lesions are inferred
      to disrupt the allocentric mapping system.

PMID- 8873267
TI  - Joint pathology and behavioral performance in autoimmune MRL-lpr Mice.
AB  - Young autoimmune MRL-lpr mice perform more poorly than age-matched controls in
      tests of exploration, spatial learning, and emotional reactivity. Impaired
      behavioral performance coincides temporally with hyperproduction of
      autoantibodies, infiltration of lymphoid cells into the brain, and mild arthritic
      like changes in hind paws. Although CNS mechanisms have been suggested to mediate
      behavioral deficits, it was not clear whether mild joint pathology significantly
      affected behavioral performance. Previously we observed that 11-week-old MRL-lpr
      mice showed a trend for disturbed performance when crossing a narrow beam. The
      first aim of the present study was to test the significance of this trend by
      increasing the sample size and, second, to examine the possibility that arthritis
      like changes interfere with performance in brief locomotor tasks. For the purpose
      of the second goal, 18-week-old mice that differ widely in severity of joint
      disease were selectively taken from the population and tested in beam walking and
      swimming tasks. It was expected that the severity of joint inflammation would be
      positively correlated with the degree of locomotor impairment. The larger sample
      size revealed that young MRL-lpr mice perform significantly more poorly than
      controls on the beam-walking test, as evidenced by more foot slips and longer
      traversing time. However, significant correlation between joint pathology scores
      and measures of locomotion could not be detected. The lack of such relationship
      suggests that mild joint pathology does not significantly contribute to impaired
      performance in young, autoimmune MRL-lpr mice tested in short behavioral tasks.

PMID- 8873268
TI  - Difference in testosterone sensitivity in male spontaneously hypertensive (SHR)
      and Wistar-Kyoto rats (WKY).
AB  - The effects of castration and testosterone substitution on copulatory behavior
      and arginine-vasopressin (AVP) concentrations in the lateral septum (LS) were
      compared in the male spontaneously hypertensive rat (SHR) and its normotensive
      counterpart, the Wistar-Kyoto rat (WKY). The copulatory behavior was attenuated
      in the intact SHR and remained for a shorter time after castration than in the
      WKY males. A higher dose (1 mg/kg) of testosterone propionate (TP) was required
      in the castrated SHR to reestablish the copulatory behavior compared to the WKY
      (0.5 mg/kg). Following castration the main decline of AVP concentrations occurred
      over a period of 28 days. On postcastrational day 14, a time when approximately
      50% of the initial AVP concentration remained, the decrease in the LS AVP content
      of the SHR surpassed that of the WKY. A dose-dependent increase of the AVP
      concentrations was achieved after 3 weeks of TP treatment (0.5 and 1.0 mg/kg,
      SC), which commenced 28 and 56 days after castration. The increase of AVP
      concentrations in the LS after a submaximal dose of TP (0.5 mg/kg) was less in
      the SHR than in the WKY. It is concluded that the gonadal hormone control of the
      copulatory behavior and AVP content in the terminal fields of the LS is
      characterised by a lower sensitivity in the SHR compared to the WKY. The data
      suggest that the low responsiveness to testosterone in the SHR comprises
      hypothalamic as well as extrahypothalamic neurons.

PMID- 8873269
TI  - Hypothalamic obese, functionally castrated hens are hypersensitive to estrogenic
      modulation of lipid metabolism.
AB  - Estradiol benzoate (E2) increases plasma lipids in hypothalamic obese,
      functionally castrated (OFC), obese laying (OL), and control laying hens (CONT).
      However, E2 reduces fattiness in OFC but not in OL or CONT hens. Antiestrogen,
      such as tamoxifen (TAM), reduces plasma lipids in OL and CONT, but not in OFC,
      hens and has no effect on fattiness in any of them. Apolipoprotein VLDL-II (apo
      VLDL-II), lipoprotein lipase (LPL), and rate of lipolysis may mediate these
      estrogenic effects. In the present study, effects of E2 and TAM on fattiness,
      plasma apo-VLDL-II, in vitro lipolysis, and LPL activity in postheparin plasma
      and abdominal adipose tissue (AAT) were determined in OFC, OL, and CONT hens.
      Basomedial hypothalamic lesions were performed in 3-month-old White Leghorn hens.
      At the static phase, 10 months later, OFC OL, and CONT hens were divided into
      three subgroups and injected IM on alternate days, with either 2 mg E2/kg b.wt.,
      10 mg TAM/kg, or vehicle corn oil, for 5 weeks. In OL and OFC hens, body and AAT
      weights were higher than in CONT poullets. Food intake and ovarian weight were
      similar in OL and CONT, higher than in OFC hens. Plasma LPL activity was higher,
      whereas plasma apo-VLDL-II and stimulated lipolysis were lower in OFC than in OL
      and CONT hens. In OFC hens LPL activity per unit of AAT was half than in OL and
      CONT. Total LPL activity in AAT was similar in OFC and CONT and higher in OL
      hens. Levels of basal lipolysis were similar in all experimental hens. TAM did
      not affect any of the measured parameters in OFC hens. In OL and CONT hens, TAM
      depressed apo-VLDL-II, increased plasma LPL activity, but had no effects on AAT
      LPL activity, on stimulated lipolysis, or fattiness. E2 increased apo-VLDL-II to
      similar levels in all groups and reduced LPL activity in plasma and AAT of obese
      hens. Only in OFC hens did E2 enhance basal and stimulate lipolysis and reduce FI
      and fattiness. We conclude that in adult laying hens, unlike in cockerels and
      juvenile hens, estrogen reduces lipid incorporation in fat depots by enhancing
      apo-VLDL-II production that reduces plasma and AAT LPL activity. This may
      increase lipoprotein available for incorporation into developing yolks. The lack
      of estrogen in OFC hens reduces circulating apo-VLDL-II and thus increases LPL
      activity and amount of fat depots.

PMID- 8873270
TI  - Habituation of airpuff-elicited cardiovascular responses in the spontaneously
      hypertensive rat.
AB  - Repeated delivery of fast rise-time acoustic stimuli elicit cardiac changes in
      humans that reflect startle, orienting, and defense responses. To test the
      hypothesis that fast rise-time stimuli produce these responses in the rat, we
      evaluated magnitude, latency, and habituation of cardiovascular responses to
      brief airpuff stimuli in normotensive rats. We also evaluated airpuff-elicited
      cardiovascular responses in spontaneously hypertensive rats. In addition to a
      robust increase in blood pressure, airpuffs produced one or more of three
      sequential heart-rate responses in normotensive rats--first, short-latency
      tachycardia (latency ).8 s), then rapidly habituating bradycardia (latency 2.2
      s), then long-latency tachycardia (latency 3.5 s)--which likely reflected
      startle, orienting, and defense responses, respectively. Airpuffs rarely produced
      bradycardia in hypertensive rats, suggesting that this strain does not
      appropriately orient to sensory stimuli. In addition, compared to normotensive
      rats, hypertensive rats exhibited greater between-session habituation of long
      latency tachycardia and blood pressure increases. This finding contrasts with the
      Folkow hypothesis, which assumes that, in subjects with a genetic predisposition
      to develop hypertension, sympathetic responses will remain exaggerated after
      repeated stimulation, thus contributing to thickening of the arterial
      vasculature.

PMID- 8873271
TI  - Rats integrate meal cost and postoral changes in caloric density.
AB  - Rats can maintain energy intake in response to changes in the caloric density of
      food by compensatory shifts in the number and size of meals. This study
      challenged rats' regulation of intake in two ways: manipulating the caloric
      density covertly to remove orosensory cues and altering baseline meal patterns by
      increasing the cost of obtaining meals. Rats with gastric catheters were
      maintained on a complete liquid diet delivered by pumps to a drinking spout and
      to the stomach; within meals, a rat's licking at the spout controlled the timing
      and duration of the simultaneous isovolemic intragastric infusions. Prior to each
      meal, some of the rats were required to press a bar to activate the spout
      mechanism; when the meal cost was paid, a cue light signaled that licks would
      deliver food. The light remained on until the rat ceased licking for 10
      consecutive min; to resume feeding, the rat had to pay the cost again. The
      standard diet pumped to the spout was prepared at 1 kcal/g; the intragastrically
      co-infused diet varied from 0 (water) to 2 kcal/g in 0.5-kcal/g increments. Each
      concentration was presented for at least 4 days. Separate groups of rats were
      studied at no cost, low cost (5 bar presses/meal), and high cost (80 bar
      presses/meal). As the infusate concentration increased, the rats ate fewer meals
      per day. Meal size by weight decreased as caloric density increased, with he
      largest meals taken when water was infused. Caloric meal size increased linearly
      with caloric density for all groups. Meal sizes in the low-cost group were
      similar to those of the no-cost group, but the latter took more meals per day
      and, therefore, consumed more total calories. High-cost meal patterns were
      parallel to those of the other groups, but with fewer, larger meals. All groups
      maintained a constant daily caloric intake across infusate concentrations. Meal
      patterns changed rapidly in response to these "covert" (untasted, isovolemic)
      changes in caloric density. Rats can, thus, integrate the cost of obtaining food
      and its postingestive benefits in the absence of mediating orosensory cues.

PMID- 8873272
TI  - The 5-HT1B receptor agonist CP-94,253 reduces food intake and preserves the
      behavioural satiety sequence.
AB  - The 5-HT1B receptor has been proposed as a link in the relationship between
      serotonin and satiety. However, the anorexia induced by RU-24969, a 5-HT1A/1B
      agonist, has been shown to delay behaviours associated with the onset of satiety,
      increase the frequency of intake and increase some nonfeeding activities. CP
      94,253 is a highly selective agonist at the 5-HT1B receptor site with less
      affinity for other receptor sites, and has been used in this study to determine
      if agonism of 5-HT1B receptor sites adjust the behavioural satiety sequence in a
      way consistent with satiety. The effects of an ED50 of dose of CP-94,253 (5.0
      mg/kg, IP) on eating behaviour of the fasted rat were monitored. Temporal
      profiles of behaviour duration and frequency were generated. Food intake was
      reduced 57% by CP-94,253 (p < 0.0005). Analysis confirmed that CP-94,253 reduced
      rearing (p < 0.05) and increased resting (p < 0.05) but preserved the overall
      pattern of the satiety sequence. Increased locomotion was not significant and
      caused no gross disruption of the behavioural repertoire. Such changes are also
      produced by prefeeding. In a second experiment, RU-24969 (1.0 mg/kg, IP) reduced
      food intake by only 30% (p < 0.05) However, RU-24969 markedly disrupted the
      satiety sequence profile, which did not resemble the profile produced by
      prefeeding. RU-24969 presumably induces this disruption via a mechanism other
      than 5-HT1B activation. The use of CP-95,253 demonstrates that selective
      activation of 5-HT1B receptor sites is sufficient to reduce food intake and
      enhance satiety as represented by the behavioural satiety sequence.

PMID- 8873273
TI  - Estimated magnitude of behavioral effects of phenytoin in rats and its
      reproducibility: a collaborative behavioral teratology study in Japan.
AB  - A collaborative study was conducted by 30 laboratories that participated in the
      Behavioral Teratology Meeting in Japan. Pregnant Sprague-Dawley rats from four
      breeders were orally administrated 200 mg/kg of phenytoin each day from day 10 to
      day 14 of gestation. The offspring were tested for behavioral teratogenic effects
      at various ages. The effects were estimated in terms of common effect size, which
      should be very resistant to the variation inevitable in behavioral teratology
      results, and thus yield a different type of information from that reported in the
      usual behavioral teratology studies. The common effect size also gives
      information on the magnitude of the behavioral teratogenic effects that previous
      studies could not provide. A breeder difference in the effect of phenytoin for
      several measures was found in terms of common effect size. The estimated
      phenytoin effect was found to be large enough to be detected by using a sample
      size of 20 per group. As to reproducibility of results, estimation by standard
      deviation across laboratories disclosed that there was almost no difference in
      magnitude between behavioral and non-behavioral measures, indicating that much of
      the variation in behavioral teratology results of phenytoin might not be due to
      measurement error from behavioral tests but rather to the phenytoin effect itself
      administered via the mother. How seriously a single study is affected by
      uncontrollable variation of results was illustrated by plotting the respective
      laboratory results on a dimension. A standard practice in the interpretation of
      discrepancies among results obtained from single studies is criticized; it is
      pointed out that such interpretations rely on an optimistic assumption: that is,
      that results obtained from single studies would be free from the usual variation
      of results found in behavioral teratogenic research.

PMID- 8873274
TI  - Effect of umami taste on pleasantness of low-salt soups during repeated testing.
AB  - In the present study the effects of the umami substances, monosodium glutamate
      (0.2%) and 5'-ribonucleotides (0.05%), on the acceptance of low-salt soups in two
      groups of subjects, one with low-salt (n = 21) and the other with high-salt (n =
      23) preferences were assessed. The groups were presented with soups containing
      0.3% sodium chloride (low-salt group) and 0.5% sodium chloride (high-salt group).
      The subjects three times consumed leek-potato or minestrone soup with umami and
      three times the other soup without umami during six sessions over 5 weeks
      (sessions 2-7). In addition they tasted these and two other soups (lentil and
      mushroom soup) during sessions 1 and 8, during which they evaluated the
      pleasantness, taste intensity, and ideal saltiness of the soups with and without
      added umami. These ratings were higher when soups contained umami in both the low
      and high-salt groups, and they remained higher regardless of which of the soups
      served for lunch contained umami. The low- and high-salt groups did not differ in
      pleasantness ratings, although the former rated the taste intensity of their
      soups higher and ideal saltiness closer to the ideal than did the latter. The
      pleasantness ratings of soups without umami were significantly lower at the end
      of the study than at the beginning, whereas those of soups with umami remained
      unchanged. These data suggest that the pleasantness of reduced-salt foods could
      be increased by addition of appropriate flavors.

PMID- 8873275
TI  - Rhythms of body temperature and temperature selection are out of phase in a
      diurnal rodent, Octodon degus.
AB  - Individual Chilean degus (Octodon degus) were maintained in a thermal gradient
      (14 degrees C to 33 degrees C) for two or more weeks under a 14L:10D light-dark
      cycle. All animals showed robust daily rhythms of body temperature and locomotor
      activity consistent with the diurnal habits of the species. They also showed a
      robust daily rhythm of temperature selection 180 degrees out of phase with the
      rhythms of body temperature and locomotor activity. These results in a diurnal
      species extend previous findings of a 180 degrees phase difference between the
      rhythms of body temperature and temperature selection in nocturnal rodents. The
      asynchrony between these two rhythms implies an opposition between the circadian
      system (responsible for the generation of the body temperature rhythm) and the
      homeostatic system (responsible for the behavioral response of temperature
      selection that opposes the body temperature rhythm.

PMID- 8873276
TI  - Seasonal changes in urinary odors and in responses to them by blind subterranean
      mole rats.
AB  - Breeding and nonbreeding season male and female mole rats from two chromosomal
      species of the Spalax ehrenbergi superspecies were tested in a tunnel T-maze to
      assess their responses to urine collected from breeding- and nonbreeding season
      male and female conspecific and heterospecific donors. The results indicate that
      S. ehrenbergi mole rat urine contains species-, sex-, and season-specific
      chemosensory cues and that male and female mole rats change their responses to
      these chemosensory cue depending upon the season. During the nonbreeding season,
      mole rats avoid conspecific and heterospecific urine of both sexes. In contrast,
      during the breeding season, mole rats do not avoid conspecific urine and males do
      not avoid heterospecific urine. These changes in responses to the chemosensory
      cues in urine are adaptive to their seasonal life underground because they could
      help the animals avoid aggressive encounters during the nonbreeding season and
      facilitate their approaching potential mates and competitors during the breeding
      season. The results suggest that chemical communication could play a role in
      social encounters, reproduction, and species isolation in the S. ehrenbergi
      superspecies.

PMID- 8873277
TI  - Effect of repeated stress on a number of plasma amino acids and related compounds
      in young and old rats.
AB  - A number of amino compounds were studied in the plasma of young and old rats
      exposed to an immobilization stress on 3 different days. Baseline values were
      similar for all compounds between age groups except for slightly higher
      phenylalanine levels in old animals. Most differences were seen in the stress
      responses. Stress response intensities for alanine, aspartic acid, methionine,
      phenylalanine, and tyrosine were generally higher in old rats and recovery times
      from stress were usually longer. Although the stress responses decreased in young
      rats for some compounds over the three exposures, old rats showed no or less
      adaptation during this time. All the other amino acids showed no marked age
      effects. This study shows that certain plasma amino acids can serve as selective
      indicators of biological age and that their stress responses might be better
      markers of the aging process than their resting levels.

PMID- 8873278
TI  - Glutamine metabolism is changed in lymphocytes from aged rats.
AB  - Changes in the protein content, maximal activity, and Km of phosphate-dependent
      glutaminase were measured in the lymphoid organs (thymus, spleen, and mesenteric
      lymph nodes) from just-weaned, mature (3 months), and aged rats (15 months).
      Also, [U-14C] glutamine transport and decarboxylation and the production of
      glutamate and aspartate from 2 and 20 mM glutamine were measured in incubated
      mesenteric lymph node lymphocytes. The ageing process induced a reduction in the
      protein content of the thymus and spleen, as well as the phosphate-dependent
      glutaminase activity in the thymus and isolated lymphocytes. The Km of phosphate
      dependent glutaminase, however, was not affected by the process. Ageing reduced
      [U-14C] glutamine decarboxylation and increased glutamate and aspartate
      production in incubated lymphocytes. The results indicate that the ageing process
      does modify several aspects of glutamine metabolism in lymphocytes: reduces
      maximal glutaminase activity and [U-14C] glutamine decarboxylation and increases
      the Km for [U-14C] glutamine uptake and the production of glutamate and
      aspartate.

PMID- 8873279
TI  - Antinociceptive action of vaginocervical stimulation in rat spinal cord: 2-DG
      analysis.
AB  - Using [14C] 2-deoxyglucose (2-DG) autoradiography with computerized densitometric
      analysis, unilateral foot pinch was found to significantly increase the relative
      optical density in laminae I and II of the ipsilateral, compared to the
      contralateral, spinal cord at lumbar 5 (L5). However, during vaginocervical
      mechanostimulation applied concurrently with the unilateral foot pinch, no
      comparable difference was observed. No response to foot pinch was observed in
      other laminae of the spinal cord at L5, and no effects comparable to the above
      were observed at L3. These findings indicate that vaginocervical
      mechanostimulation suppresses neural responses to noxious foot pinch stimulation
      selectively at the laminae I and II level of the spinal cord at L5, but not at
      L3.

PMID- 8873280
TI  - The circadian rhythm of cortisol in the saliva of young pigs.
AB  - Single and population-mean cosinor analyses document a circadian rhythm in
      salivary cortisol of pigs (p < 0.001). The midline estimated statistic of rhythm,
      the MESOR (M), is 1.50 +/- 0.07 ng/ml. For the group of 14 pigs studied there was
      a predictable variation of 64% around this mean in salivary cortisol within a
      day: the double circadian amplitude, 2A, was 0.96 ng/ml, with a 95% confidence
      interval ranging from 0.60 to 1.32 ng/ml. A measure of timing, the acrophase,
      phi, was 10 h 52 min from the phase reference (0030, the middle of the daily dark
      span of the 24-h light-dark cycle in which the pigs were kept). The 95%
      confidence interval of phi extended from 9 h 48 min to 12 h 12 min from the
      reference time. The chronobiologic approach provides indispensable quantitive
      characteristics as reference standards for future basic or applied work.

PMID- 8873281
TI  - Circadian body temperature rhythms of the solitary cape mole rat Georychus
      capensis (Bathyergidae).
AB  - Simultaneous measurements of activity and telemeterized body temperature were
      measured under 12:12 LD and constant light conditions in the solitary,
      subterranean rodent Georychus capensis for 137 consecutive days. The objectives
      of the study were twofold: a) to determine whether G. capensis display circadian
      body temperature rhythms similar to those of nonsubterranean mammals, and b) to
      determine whether body temperature rhythms provide a more reliable measure than
      those of activity of endogenous circadian rhythms under laboratory conditions.
      Significant circadian Tb and activity rhythms were recorded under entrained and
      free-running conditions (i.e., under a light-dark cycle and under constant
      illumination), confirming the ability of this species to perceive light. Although
      the maximum daily amplitude of Tb (Rt) between the mean photophase minimum and
      the mean scotophase maximum was 99% of that predicted by body mass for mammals,
      G. capensis did not display sustained differences of either the minimum, mean, or
      maximum Tb between the photo- and scotophases. Nevertheless, most individuals
      indicated nocturnal activity patterns. Evidence suggests a lack of an obvious
      endogenous body temperature rhythm. Body temperature may thus not be a reliable
      measure of endogenous circadian rhythms in this rodent.

PMID- 8873282
TI  - Appetitive sexual behavior in male rats: 1. The role of olfaction in level
      changing behavior.
AB  - Level-changing behavior is a form of anticipatory behavior of a male rat, when
      tested in a bilevel testbox. The male explores the testcage prior to introduction
      of a female. The female is introduced after 5 min. The number of level changes
      displayed by the male in this period reflects appetitive aspects of sexual
      behavior and it was suggested that analysis of this level-changing behavior may
      function as assessment of sexual motivation. In this study the increase of
      anticipatory level changes over repeated weekly tests was dependent upon (sexual)
      olfactory stimulation. The number of anticipatory level changes was reliably
      reduced by administration of the opioid antagonist naloxone, suggesting that
      endogenous opioids facilitate this behavior. These results suggest that the
      increase of anticipatory level changes over repeated tests is a response to
      olfactory stimuli and reflects appetitive aspects of sexual behavior, which are
      stimulated by endogenous opioids. These results are in accordance with the
      concept that analysis of anticipatory level-changing behavior can be used to
      assess sexual motivation.

PMID- 8873283
TI  - Appetitive sexual behavior in male rats: 2. sexual reward and level-changing
      behavior.
AB  - Anticipatory level-changing behavior is a form of appetitive sexual behavior
      displayed by male rats prior to introduction of a female in a bilevel testbox.
      Analysis of this level-changing behavior may serve as assessment of sexual
      motivation. Because ejaculation affects appetitive aspects of sexual behavior,
      measures purporting to assess sexual motivation should be effected by
      ejaculation. We observed that ejaculation prior to testing reduced the number of
      anticipatory level changes of a male rat. This reduction was greater when tested
      after two than after one ejaculation. Our results support the concept that
      analysis of anticipatory level-changing behavior can be used to measure sexual
      motivation.

PMID- 8873284
TI  - Differential effects of prenatal protein malnutrition and prenatal cocaine on a
      test of homing behavior in rat pups.
AB  - The effects of prenatal cocaine exposure and protein malnutrition on orientation
      to home nest material was assessed in rat pups. Sprague-Dawley dams were fed a
      diet of low protein content (6% casein), and isocaloric diet of adequate protein
      content (25% casein, control), or a laboratory chow diet prior to mating and
      throughout pregnancy. Within each diet group, rats received either cocaine
      injections (30 mg/kg IP 2 times per week prior to mating and the 30 mg/kg SC
      daily from day 3 to 18 of pregnancy) or saline injections. All litters were
      fostered on the day of birth to control mothers fed an adequate diet. On
      postnatal days 7, 9, and 11, a single pup from each litter (n = 11-15 per
      treatment) was tested repeatedly in a clean test cage for the rapidity of
      approach, and level of attraction to their own home (nest) bedding compared with
      fresh bedding. Prenatal malnutrition and prenatal cocaine exposure each gave rise
      to independent effects on performance, based upon factor analysis. Prenatal
      malnutrition, but not prenatal cocaine increased the time taken for rat pups to
      approach their nest bedding, reduced the time spent on this bedding, decreased
      the number of entries into the sector containing the home bedding and reduced pup
      weight. Prenatal cocaine, but not prenatal malnutrition, produced a reduction in
      activity, but had no effect on pup weight. The lower activity level was most
      pronounced on postnatal day 7. Surprisingly, interactive effects of prenatal
      cocaine and prenatal malnutrition were not observed on any behavior examined.
      Nevertheless, the co-existence of drug addiction and malnutrition in human
      populations raises the possibility that some of the effects generally attributed
      to drug exposure may, in fact, be due to malnutrition.

PMID- 8873285
TI  - Artificial eggs: measuring heart rate and effects of disturbance in nesting
      penguins.
AB  - A technique for the noninvasive measurement of heart rate in incubating penguins
      is described and evaluated. The technique uses an artificial egg fitted with an
      infrared sensor. Placing the egg in the nest causes minimal disturbance to the
      resident penguin; this penguin is then paint-marked so that subsequent
      measurements may be taken from the unmarked, naive partner once it assumes
      incubation. Heart rate changes are useful indicators of nesting penguins'
      reactions to events in their environment because often their behaviour does not
      appear to vary in response to a threat until the point at which they flee,
      exposing eggs and chicks to predators. The eggs can be readily transferred from
      one nest to another. They have been successfully deployed on both African
      (Spheniscus demersus) and Gentoo Penguins (Pygoscelis papua). The design should
      be readily adaptable for use with other seabirds and passerines.

PMID- 8873286
TI  - Effect of pyloric cuffs on cholecystokinin satiety.
AB  - Because inflation of a pyloric cuff during feeding blocks gastric emptying and
      increases gastric distention, this device was used to test the hypothesis of
      synergism between gastric distention and cholecystokinin octapeptide (CCK-8) in
      reducing intake. Adult, male Sprague-Dawley rat were allowed 20-min access to 30%
      sucrose, with or without inflation of pyloric cuffs, after intraperitoneal
      injection of saline or 1, 2, or 4 micrograms/kg CCK-8. Cuff inflation resulted in
      large increases in gastric volume at the end of feeding tests. However, this
      manipulation failed to enhance the effectiveness of any dose of CCK-8. In fact,
      data analyses revealed trends suggestive of decreased effectiveness of the two
      lowest doses under these conditions. The effect of 4 micrograms/kg CCK-8 was
      almost identical in tests with and without cuff inflation. These results are
      contrary to the prediction of greater potency of CCK-8 resulting from increased
      gastric distention.

PMID- 8873288
TI  - Testosterone and sex role identification in lesbian couples.
AB  - Within the lesbian community there exists a common perception that lesbians
      comprise two types, "butch," having more masculine characteristics, and "femme,"
      having more feminine characteristics. The present study investigated the question
      of whether these perceptions are reflected in different levels of the
      predominantly male hormone testosterone. Salivatory testosterone levels and
      "butch/femme" ratings were obtained from 28 lesbian couples. Individuals within
      couples tended to be opposite in "butch/femme" ratings [intraclass r(26) = -0.77,
      p < 0.0001] but similar in testosterone levels [intraclass r(26) = 0.47, p
      <0.01]. Also within couples, individuals with higher "butch" ratings had
      significantly higher testosterone levels, although across all individuals as a
      whole (ignoring couple pairing) there was no correlation between testosterone and
      "butch/femme" ratings. The results indicate that testosterone is related to
      "butch/femme" characteristics, but only when regarded within the couple
      relationship.

PMID- 8873287
TI  - Lordosis-inhibiting effect of progesterone in female rats with lesions in septum,
      preoptic area, or dorsal raphe nucleus.
AB  - Radiofrequency lesions in the septum (SL), the preoptic area (POAL), or the
      dorsal raphe nucleus (DRL) were made in ovariectomized rats. In a control group
      of 16 females, ovariectomy, but no brain surgery, was performed. All animals
      except half of the control rats received injections of 5 mg progesterone (P) 1 h
      prior to the injection of 5 micrograms/kg b.w. of estradiol benzoate (EB).
      Instead of 5 mg P, oil was administered to half of the controls. Forty-four hours
      after EB, all females received 0.5 mg P. A sexual behavior test was performed 4 h
      after the last injection of P. The result was that oil-treated control rats
      showed high lordosis quotient (LQ) and soliciting behavior. In contrast, low
      scores of LQ and no soliciting behavior were observed in all of the 5 mg P
      treated rats, even if the SL, POAL, or DRL was made. These results suggest that
      the septum, the preoptic area, and the dorsal raphe nucleus are not essential for
      the female sexual behavior-inhibiting mechanisms of progesterone.

PMID- 8873289
TI  - A modified stereotaxic device for small bird anaesthesia and neurosurgery.
AB  - This report describes simple modifications to a stereotaxic instrument that allow
      for the administration of an inhalant anaesthetic and provide improved access to
      avian dorsal forebrain structures along with a more natural orientation for small
      birds during neurosurgery.

PMID- 8873290
TI  - Short-term consumption of a diet rich in fat decreases anxiety response in adult
      male rats.
AB  - Short- and long-term changes in the composition of dietary macronutrients
      [protein (P), carbohydrate (C), and fat (F)] alter neurochemistry and behavior in
      animals. We examined whether short-term intake of a diet rich in P, C, or F
      affected their anxiety response (AR). AR of Sprague-Dawley rats was measured in
      an elevated plus maze. Rats were placed in the black compartment facing the wall
      opposite the aperture, and the time (max. 360 s) it took to enter the white
      compartment with all four paws was noted. Rats were fed Purina chow and tap water
      unless otherwise indicated. On repeated testing (three times on the same day) AR
      increased and, consequently, most rats spent the entire 360 s in the dark.
      Whereas most rats exhibited low anxiety response in trial 1, which increased
      during successive trials (low-high group), some exhibited high initial anxiety
      that remained unchanged (high-high group). To determine whether macronutrients
      may alter AR, groups of low-high and high-high rats were tested three times on
      the same day and then put on a P, C, or F diet for 7 days. On day 8, they were
      again tested for AR in a single trial and the results compared with those of the
      third trial of the previous test (preC: 302 +/- 39, post-C: 294 +/- 42, p > 0.05;
      pre-P: 305 +/- 35, post-P: 297 +/- 43, p > 0.05; pre-F: 321 +/- 17, post-F: 241
      +/- 24sec, p = 0.009; n = 30; mean +/- SEM). The results show that a diet rich in
      F, but not P or C, decreases AR in rats.

PMID- 8873291
TI  - Smoking and vulnerability for schizophrenia.
AB  - In several countries, the prevalence of smoking among schizophrenia patients is
      extraordinarily high (70% or greater). A State hospital survey demonstrated that
      after correcting for other factors, inpatients who have schizophrenia are more
      likely to be smokers than are persons in the normal population or even other
      chronic psychiatric inpatients. These findings suggest that neuroleptic treatment
      and the hospital environment cannot completely explain the high prevalence of
      smoking. The relationship between smoking and schizophrenia may be explained by a
      combination of three factors. One factor is the great difficulty for
      schizophrenia patients to quit smoking. Another is late onset: some schizophrenia
      patients start to smoke after the onset of psychosis. A third is increased early
      onset: schizophrenia patients may start daily smoking in greater numbers during
      adolescence (before the onset of their psychosis) than do persons in the normal
      U.S. population. Daily smoking is usually considered a sign of nicotine addiction
      and is used by epidemiological surveys to define the prevalence of smokers (most
      smokers smoke daily and very few smokers do not smoke every day). The increased
      early onset suggests that familial factors may increase the prevalence of smoking
      even among patients who have not yet shown psychotic symptoms. It is hypothesized
      that smoking among family members in families with genetic loading for
      schizophrenia may be a marker for those at risk of developing schizophrenia.

PMID- 8873292
TI  - Medical comorbidity and schizophrenia: editors' introduction.
AB  - Schizophrenia is a heavily biologically determined psychiatric disorder with
      unequivocal evidence for a major genetic component in its transmission. In
      addition to its genetic determination, schizophrenia is also associated with
      increased morbidity and mortality with illness and suffering and with death rates
      that are higher than would be expected. One of the intriguing possibilities is
      that there may be some biological link between genetic predisposition to
      schizophrenia and to other medical diseases. This research on medical
      comorbidity, originally presented at the Tenth Annual Pennsylvania Conference on
      Schizophrenia at Norristown State Hospital, requires further research and
      understanding.

PMID- 8873293
TI  - Medical comorbidity in schizophrenia.
AB  - The extent and consequences of medical comorbidity in patients with schizophrenia
      are generally underrecognized. Patients with comorbid conditions are usually
      excluded from research studies, although they probably represent the majority of
      individuals with schizophrenia. Elderly patients are especially likely to have
      comorbid disorders. In this article, we review selected literature on medical
      comorbidity in schizophrenia, including physical illnesses, substance use,
      cognitive impairment, sensory deficits, and iatrogenic comorbidity. Data from the
      University of California, San Diego Clinical Research Center on late-life
      psychosis are also presented. Older schizophrenia patients report fewer comorbid
      physical illnesses than healthy comparison subjects, but their illnesses tend to
      be more severe. These results suggest that schizophrenia patients may receive
      less than adequate health care. Substance abuse is more common in patients with
      schizophrenia than in the general population and may exacerbate psychiatric
      symptoms in these patients. Although generalized cognitive impairment is
      associated with schizophrenia, the main contributors to dementia in older
      patients are more likely to be comorbid neurological and other physical
      disorders, substance abuse, and medication side effects. Iatrogenic comorbidity
      results primarily from the use of neuroleptic (e.g., tardive dyskinesia) and
      anticholinergic (e.g., confusion) medications. Clinical and research
      recommendations are made for management of comorbidity in schizophrenia.

PMID- 8873294
TI  - Nicotinic receptor function in schizophrenia.
AB  - Schizophrenia can be partially characterized by deficits in sensory processing.
      Biochemical, molecular, and genetic studies of one such endophenotype, the P50
      auditory-evoked potential gating deficit, suggest that one of the neuronal
      nicotinic receptors, the alpha 7 nicotinic receptor, may function in an
      inhibitory neuronal pathway involved in this phenotype. The P50 deficit is
      normalized in nongating subjects by nicotine. Although most schizophrenia
      patients are heavy smokers, the effects of nicotine may be transient, as alpha 7
      receptors are known to desensitize rapidly. In an animal model of the P50 gating
      deficit, antagonists of the alpha 7 nicotinic receptor block normal gating of the
      second of paired auditory stimuli. Regional localization of receptor expression
      includes areas known to function in sensory filtering. An inhibitory mechanism,
      in the hippocampus, may involve nicotinic stimulation of gamma-aminobutyric acid
      (GABA)ergic interneurons, resulting in decreased response to repetitive stimuli.
      Expression of the alpha 7 receptor is decreased in hippocampal brain tissue,
      dissected postmortem, from schizophrenia subjects. The P50 deficit is inherited
      in schizophrenia pedigrees, but it is not sufficient for disease development and
      thus represents a predisposition factor. Linkage analysis between the P50 deficit
      in multiplex schizophrenia pedigrees and deoxyribonucleic acid (DNA) markers
      throughout the genome yielded positive lod scores to DNA markers mapping to a
      region of chromosome 15 containing the alpha 7 nicotinic receptor gene.
      Elucidation of possible interactions of the P50 with other factors, known to be
      important in the etiology of the disease, is important in determining an overall
      pathobiology of schizophrenia.

PMID- 8873295
TI  - Accelerated osteoporosis in psychiatric patients: possible pathophysiological
      processes.
AB  - Osteoporosis, a very prevalent, potentially debilitating disease, is
      characterized by decreased bone mineral density (BMD). Decreased BMD has recently
      been reported in patients suffering from several mental disorders, including
      schizophrenia and major depression. In these patients the accelerated decrease in
      BMD can be attributed to drug-induced decreases in levels of estrogen and
      testosterone, to polydipsia and decreased calcium to smoking and alcoholism, and
      to increased activity of several interleukins as well as to hyperprolactinemia
      and hypercortisolemia. Several of these processes may be prevented or altered in
      order to prevent or delay decreased BMD.

PMID- 8873296
TI  - Problems and progress in the diagnosis and treatment of polydipsia and
      hyponatremia.
AB  - Fluid-electrolyte balance is regulated within a narrow range and disturbances in
      this system are unusual in animals and humans. Studies from the preneuroleptic
      era to date suggest that up to 25 percent of patients with schizophrenia have
      polydipsia, suggesting that it is related to the pathophysiology of the
      psychoses. Polydipsia and the related phenomenon of hyponatremia cause
      considerable mortality and morbidity. Prevalence studies are limited by imprecise
      measures available at present. The treatment was limiting water intake when
      patients reached critical levels of water retention, which however did not
      improve polydipsia. Recent case reports and open studies have shown that
      clozapine improves both polydipsia and water retention. The response occurs at
      low doses and is not related to improvement in psychosis. This may not be
      applicable to all patients and better understanding of the pathophysiology of
      polydipsia-hyponatremia would lead to more empirically derived treatments.

PMID- 8873297
TI  - Schizophrenia and HIV.
AB  - There is very little published information regarding the co-occurrence of human
      immunodeficiency virus (HIV)-spectrum illness and psychotic illnesses, including
      schizophrenia, even though their coexistence in the same patient may severely
      affect the course of both illnesses. Estimates of the frequency of HIV infection
      in patients with preexisting mental illness range between 5 and 7 percent.
      Estimates of new-onset psychosis in patients with HIV-spectrum illness range
      between 0.2 and 15 percent and may increase as the stage of HIV illness
      progresses. Regardless of which illness came first, their occurrence together
      appears to be associated with more morbidity and mortality than would be expected
      with either illness alone. Patients with new-onset psychosis respond to and
      tolerate relatively low doses of antipsychotic medication. Whether the presence
      of HIV decreases the effective daily dose of neuroleptic medication in patients
      with preexisting psychosis is not yet known. A clearly superior neuroleptic
      medication for patients with both psychosis and HIV infection has not yet been
      identified. Further systematic exploration is needed.

PMID- 8873298
TI  - Medical complications of new antipsychotic drugs.
AB  - Although antipsychotic drugs have a high therapeutic index (ratio of clinical
      benefit to adverse effects), they are associated with a range of adverse effects
      in most patients. The majority of these side effects are tolerable, readily
      managed, and not life threatening. The most troublesome side effects are
      neurological. Two new antipsychotics (clozapine and risperidone) have recently
      been introduced and are the first of a new generation of compounds that may
      further improve the therapeutic index of routine antipsychotic drug
      administration. Clozapine clearly has a reduced risk of drug-induced
      parkinsonism, akathisia, and tardive dyskinesia, while producing an increased
      risk of agranulocytosis, seizures, and weight gain. Risperidone at low doses
      produces relatively few parkinsonian side effects, but it can cause tardive
      dyskinesia (though relative risk remains to be established). Risperidone has not
      been associated with blood dyscrasias or increased risk of seizures, but weight
      gain can be a problem for some patients. Neuroleptic malignant syndrome has been
      reported with both drugs, but relative risk has not been established.

PMID- 8873299
TI  - Mortality among patients with schizophrenia.
AB  - Results from a 40-year followup study of psychotic patients are presented to
      illustrate some of the major findings and unanswered questions about excess
      mortality in schizophrenia and to suggest analytical approaches that take full
      account of the potential effects of sample heterogeneity. In this study, hospital
      diagnosed schizophrenia patients were at increased mortality risk whether or not
      they met research criteria for schizophrenia. In addition, mortality outcomes of
      several major diagnostic groups were similar despite substantial clinical and
      demographic differences between the groups at baseline. These results suggest
      that both diagnosis-specific and nondiagnostic factors are needed to account for
      excess mortality in patients with major psychiatric disorders. The issue of
      heterogeneity is also crucial for the clinical purposes of predicting and
      ultimately reducing the mortality risk of psychiatric patients, for example, in
      delineating profiles of high-risk patients who are not necessarily typical of
      other patients with the same diagnosis.

PMID- 8873300
TI  - The factor structure of schizotypal symptoms in a clinical population.
AB  - There is some support for the hypothesis that the factor structure of
      schizophrenia symptoms is similar to the factor structure of schizotypal symptoms
      in nonschizophrenia populations. However, no studies to date have examined
      schizotypal symptoms in patients with personality disorders. In this study,
      confirmatory factor analyses were conducted to test the relative fit of several
      models of the factorial structure of schizotypal symptoms in patients diagnosed
      with personality disorders. The EQS: Structural Equations Program was used to
      analyze DSM-III symptoms of schizotypal personality disorder (SPD) based on
      structured clinical interviews with 213 patients meeting a diagnosis for at least
      one personality disorder. A subgroup of the total sample was also evaluated for
      DSM-III-R criteria (n = 143) to test competing models of the DSM-III-R symptoms
      of SPD. A three-factor model consisting of a cognitive-perceptual, interpersonal,
      and paranoid factor yielded the best fit to the data relative to the other models
      tested. These results suggest that the three-factor model of schizophrenia
      symptoms may not entirely correspond to the factors underlying milder schizotypal
      symptoms expressed in a clinical population. It is suggested that future research
      focus on both the similarities and the differences between SPD and schizophrenia.

PMID- 8873301
TI  - Self-report measures of schizotypy as indices of familial vulnerability to
      schizophrenia.
AB  - While structured psychiatric interviews have generally succeeded in identifying
      higher rates of schizotypal personality disorder in relatives of schizophrenia
      versus control probands, self-report questionnaires designed to assess schizotypy
      have been less successful at distinguishing these groups of relatives. In the
      Roscommon Family Study, an epidemiologically based, case-controlled study
      conducted in the west of Ireland, relatives were administered a short form of
      Eysenck's Psychoticism scale and shortened and modified versions of the scales
      for magical ideation and social anhedonia developed by Chapman and colleagues. We
      compared, with relatives of matched controls, relatives of four proband groups:
      schizophrenia, other nonaffective psychoses (ONAP), psychotic affective illness
      (PAI), and nonpsychotic affective illness (NPAI). Only social anhedonia scores
      successfully differentiated, at modest levels of significance, relatives of
      schizophrenia versus control probands. Levels of magical ideation did not
      distinguish relatives of schizophrenia, ONAP, PAI, or NPAI probands from
      relatives of controls. Compared to controls, ONAP probands had significantly
      elevated psychoticism scores, but no such increase was seen in relatives of
      schizophrenia, PAI, or NPAI probands. Dimensions of schizotypy assessed at
      personal interview were significantly better at differentiating relatives of
      schizophrenia and control probands than our measures of social anhedonia, magical
      ideation, or psychoticism. Although psychiatric interviews in this sample have
      shown that clinically assessed schizotypal personality disorder and traits
      strongly aggregate in relatives of schizophrenia patients, of the three self
      report instruments designed to assess schizotypy, only one even modestly
      identifies relatives of schizophrenia versus control probands. These results
      suggest that, compared with psychiatric interviews, self-report questionnaires
      are less successful at assessing underlying familial vulnerability to
      schizophrenia.

PMID- 8873302
TI  - Prenatal exposure to influenza and increased cerebrospinal fluid spaces in
      schizophrenia.
AB  - Several epidemiological studies have suggested that maternal exposure to
      influenza during midgestation is a risk factor for schizophrenia. In exploring
      the possible pathogenic mechanism, we examined the relationship between computed
      tomography structural brain measures in 83 schizophrenia patients and 113
      controls and also their risk of maternal exposure to influenza. Four brain
      measures of the cerebrospinal fluid (CSF) spaces (lateral ventricle, maximum
      third ventricle, sulcal fluid, and sylvian fissure) were investigated in relation
      to the risk exposure level. In schizophrenia patients, these measures, in
      particular sylvian fissures, were found to increase with higher levels of risk
      exposure to influenza during the susceptible period (i.e., midgestation); no such
      effect was found in controls. These results indicate that risk for midgestational
      influenza exposure is associated with generalized enlargement of the CSF spaces,
      especially in the region of the temporal lobe. The findings suggest that certain
      morphological abnormalities of the brain frequently reported in schizophrenia
      patients may be partly attributable to antenatal exposure to influenza.

PMID- 8873303
TI  - Cue availability and affect perception in schizophrenia.
AB  - This study examined affect perception in schizophrenia. Subjects were 35 patients
      with schizophrenia or schizoaffective disorder, 11 with bipolar disorder, and 19
      matched nonpatient controls. All patients were in the latter stages of an acute
      hospitalization. Measures included a videotaped test of affect perception
      administered with and without sound, two tests of facial affect perception based
      on photographs, and two measures of nonaffect perception. The patient groups did
      not differ from one another on any of the affect perception measures, and few
      differences occurred between schizophrenia patients and nonpatient controls.
      Affect perception in schizophrenia patients was not correlated with
      symptomatology or history of illness, and there were no gender differences.
      Deficits reported in prior studies may reflect limitations in the assessment
      methodology commonly employed.

PMID- 8873304
TI  - Identifying subtypes of schizophrenia by cluster analyses.
AB  - The existence of two subtypes of schizophrenia (positive and negative) is well
      established. The evidence in favor of other subtypes, particularly a disorganized
      subtype, is still the subject of some debate. The aim of the study reported in
      this article is to investigate the possibility of further subtypes of
      schizophrenia by applying a particular method of cluster analysis to a particular
      set of data. Ward's method of cluster analysis was applied to the Positive and
      Negative syndrome Scale (PANSS) scores of 138 patients, defined as having
      schizophrenia by one of four diagnostic criteria. The validity of the cluster
      solution was assessed both by examining differences between clusters on a number
      of clinical characteristics recorded for each patient and by comparing the
      results obtained from the PANSS with those derived from a cluster analysis using
      two other instruments (the Scale for the Assessment of Negative Symptoms and the
      Scale for the Assessment of Positive Symptoms). Results from the cluster analysis
      suggest the existence of at least four subtypes of schizophrenia: positive,
      negative, mixed, and disorganized. A fifth subtype includes patients with few
      symptoms, suggesting the simple schizophrenia named by Bleuler. Evidence for the
      validity of these subtypes was provided by the differences observed between the
      clusters on a number of clinical characteristics and by the similarity of the
      cluster solution obtained from the different instruments. In conclusion, the
      negative-positive dichotomy in schizophrenia is an oversimplification, and the
      existence of a more complex structure needs to be taken into account in future
      research.

PMID- 8873305
TI  - First person account: paranoid schizophrenia--a sibling's story.

PMID- 8873306
TI  - The statin trials: closing arguments in the case against cholesterol?

PMID- 8873307
TI  - Adult heart-lung and lung transplantation in Scotland.

PMID- 8873308
TI  - The role of memory clinics.

PMID- 8873309
TI  - Where have all the doctors gone--and does it matter?

PMID- 8873310
TI  - General practice blood pressure recording in Scotland: variations in the
      classification of hypertension.
AB  - A questionnaire concerning blood pressure assessment, as part of health promotion
      activity, was circulated to all 770 Gpass practices in Scotland producing a 64.6%
      response rate. The results reveal a wide range in both the systolic and diastolic
      levels chosen to classify blood pressure as normal, borderline raised or raised.
      Practices are using a variety of values to indicate hypertension when considering
      systolic and, to a lesser extent, diastolic pressure. The variations found
      suggest that both over and under treatment are a significant risk to patients.
      The introduction of the 1993 health promotion regulations means that practices
      are required to actively target their practice population for blood pressure
      assessment and appropriate intervention. We suggest that this process will be
      enhanced if doctors are encouraged to adopt the established guidelines for the
      classification of blood pressure or general practice computer software is adopted
      to offer blood pressure protocol support.

PMID- 8873311
TI  - Eye drops--the hidden poison.
AB  - Eye drops are very commonly prescribed but their potential for systemic
      absorption and serious toxicity may be forgotten. This paper examines patterns of
      prescription of eye drops in Scotland by general practitioners. A review of the
      serious systemic features and toxicity, and their management, of commonly used
      eye drops is undertaken. Practical recommendations for the monitoring of such
      effects in clinical practice are made.

PMID- 8873312
TI  - Colonic stricture in cystic fibrosis unmasked by successful transjugular
      intrahepatic portosystemic stent shunt (TIPSS).
AB  - TIPSS was successfully performed in a 10-year-old female cystic fibrosis (CF)
      patient with bleeding gastric varices due to portal hypertension; precipitation
      of portosystemic encephalopathy later unveiled the presence of a latent colonic
      stricture associated with high potency pancreatic enzymes. The unusual sequence
      of events resulting from the co-existence of two CF pathologies are described,
      and the implications of treatment discussed.

PMID- 8873313
TI  - Peritoneal mesothelioma with gastric outlet obstruction.
AB  - Peritoneal mesothelioma has been increasing in frequency since the 1960s.
      Although still a rare malignant neoplasm, early diagnosis influences prognosis.
      More common presenting features include abdominal pain, abdominal distension or a
      palpable mass; more uncommon presentations have included dysphagia secondary to
      achalasia, chronic pancreatitis and regional lymphadenopathy. We report two
      recent cases at the Southern General Hospital in Glasgow.

PMID- 8873314
TI  - The life and times of Sir James Wylie Bt., MD., 1768-1854, body surgeon and
      physician to the Czar and chief of the Russian Military Medical Department.
AB  - James Wylie was a native of Kincardine-on-Forth and completed medical training at
      Edinburgh University in 1789. He emigrated to Russia in 1790 where he joined the
      Eletsky Regiment as a surgeon. He travelled 150,000 miles in his military medical
      capacity during several campaigns including the Napoleonic wars. He became the
      favourite of three successive Czars and made an enormous contribution to
      developing medical services, both military and civil being not only a notable
      physician and surgeon but a most effective administrator.

PMID- 8873315
TI  - Age and interval for screening mammography: whom do you believe?
AB  - The purpose of this article is to help the clinician understand the benefits and
      limitations of screening mammography in the 40-49 age group. Since the benefit of
      screening mammography is well established in the literature for the 50-59 age
      group, comparison of the relevant issues is focused on similarities and
      differences between these two age groups. The incidence of breast cancer, the
      effectiveness of mammography, and the growth rates of tumors influence the
      benefit derived from screening. Available data suggest that mammography is
      equally effective in both age groups, with similar detection rates of minimal
      cancer (27 vs. 25%). The difference in estimated annual incidence between the 40
      49 and the 50-59 age group is only 8%. Since tumor growth rate seems to be faster
      in the younger age group, screening should be performed annually, starting at 40
      years of age, if it is to provide a benefit.

PMID- 8873316
TI  - Role of stereotactic breast biopsy.
AB  - Screening mammography can detect early, nonpalpable breast cancer, resulting in
      improved long-term survival and cure rates. However, greater compliance with
      screening guidelines has increased the number of mammographic abnormalities
      found. Since 75% of the surgical biopsies performed for nonpalpable lesions are
      benign, less expensive and invasive methods of diagnosis are evolving to reduce
      the cost of screening mammography programs and the number of women undergoing
      surgery for benign mammographic findings. Stereotactic needle core biopsy allows
      minimally invasive sampling of most breast lesions and generates tissue cores for
      histologic evaluation. A specific pathologic diagnosis, as well as determination
      of invasiveness, can be achieved for mass lesions. Microcalcification can also be
      sampled to diagnose in situ cancer, although the use of core biopsy for noncomedo
      intraductal cancer is still evolving. The procedure demands meticulous technique
      to assure accurate needle placement, and careful correlation of biopsy results
      and patient follow-up is mandatory. Accuracy relative to surgical biopsy of
      nonpalpable lesions has been excellent in published series. The role of this
      procedure in patients with low, intermediate, and high suspicion mammographic
      lesions is discussed.

PMID- 8873317
TI  - Management of ductal carcinoma in situ.
AB  - The management of ductal carcinoma in situ (DCIS) is one of the most
      controversial topics in the treatment of breast cancer. With the introduction and
      utilization of screening mammography, clinically occult or microscopic DCIS has
      become the most frequent presentation of this disease. Recent advances in the
      characterization of DCIS according to histologic subgroupings, size and extent of
      disease, and nuclear grade have provided important information regarding the
      natural history of this heterogeneous group of lesions. Critical issues such as
      multicentricity, occult invasion, and potential for local recurrence and axillary
      metastases have been addressed in recent series. Prospective, single institution
      trials and data from the National Surgical Adjuvant Breast and Bowel Project
      (NSABP-B17) protocol have demonstrated that in many patients with
      mammographically detected DCIS, mastectomy may be over-treatment. Treatment
      issues for DCIS now focus on the clinical selection process to identify patients
      best suited for wide local excision alone vs. wide local excision and breast
      irradiation.

PMID- 8873318
TI  - Lobular carcinoma in situ of the breast.
AB  - Lobular carcinoma in situ (LCIS) of the breast is commonly identified as an
      incidental finding in breast biopsies performed because of either a mammographic
      abnormality or a palpable mass. Although long recognized as an entity, the
      significance and optimal treatment of LCIS remains controversial. Initially
      regarded as a pre-invasive form of breast cancer analogous to ductal carcinoma in
      situ (DCIS), LCIS was treated by mastectomy. As evidence mounted for an equal
      risk of invasive carcinoma in both breasts, bilateral mastectomy was advocated by
      some. More recent studies suggest that LCIS is a marker for increased risk rather
      than a true precursor of invasive carcinoma, and this allows a more conservative
      approach. The pathologic aspects and natural history of LCIS are discussed.

PMID- 8873319
TI  - Axillary dissection: when and how radical?
AB  - Since the 1970s, axillary dissection has been regarded primarily as a staging
      procedure, with a secondary purpose of maintaining local control in the axilla.
      The widespread administration of adjuvant systemic therapy to women with breast
      cancer, as well as the increasingly frequent detection of very small breast
      cancers by mammography, has prompted an examination of the need for axillary
      dissection in all women with invasive breast cancer. This article reviews the
      rationale for eliminating axillary dissection, the incidence of nodal metastases
      in small and apparently favorable breast cancers, and discusses how often the
      findings of axillary dissection actually alter therapy in patients with
      clinically node-negative breast cancers. The extent of axillary dissection
      necessary to provide accurate staging and maintain local control is examined, and
      patients who will benefit from axillary dissection are identified.

PMID- 8873320
TI  - Breast cancer in older women: screening and selection of locoregional therapy.
AB  - As the proportion of the population older than 65 years increases during the next
      several decades, breast cancer will be a more substantial health problem for
      older women. Screening mammography detects cancers and reduces mortality from
      breast cancer in older women. There does not appear to be an inherent reason to
      impose an upper age limit for breast cancer screening. Older women with breast
      cancer who are selected for therapy on the basis of severity of comorbidity
      rather than chronological age can be safely treated using standard surgical and
      radiation procedures. The elective addition of axillary radiation to breast
      radiation after lumpectomy appears to lower risk of regional relapse vs. the
      untreated axilla, avoids the morbidity of axillary dissection, and provides the
      best local control after breast conservation surgery.

PMID- 8873321
TI  - Breast conservation: predictors and treatment of local recurrence.
AB  - Breast conservation therapy has become the preferred treatment for many Stage I
      and II breast cancers as the "Halstedian" theory of sequential spread has been
      replaced by the belief that breast cancer is a systemic disease and that local
      regional therapy has little impact on overall survival. Local recurrence after
      conservation therapy is reportedly dependent upon a number of pathological,
      clinical, and treatment factors. This review examines the complex relationships
      among these factors, their ability to predict for residual disease within the
      breast, and its correlation with risk for local recurrence. A local recurrence
      does not appear to affect overall survival, and salvage therapy provides
      excellent local control in the majority of cases. The proper salvage therapy is
      evolving, with mastectomy the current standard. However, repeat wide-excision
      surgery may offer good local control in a select group of patients.

PMID- 8873322
TI  - Is it time to develop an optimal endocrine therapy for premenopausal patients
      with axillary node positive and negative breast cancer?
AB  - One hundred years ago ovarian ablation was shown to be an effective treatment for
      advanced breast cancer in premenopausal women. Since that time many different
      treatment modalities have been advocated to improve patient survival. The value
      of adjuvant ovarian ablation, however, has recently been established in the
      overview of breast cancer clinical trials. In fact, comparison of the efficacy of
      combination chemotherapy with earlier trials of oophorectomy demonstrate the
      superiority of oophorectomy. The effectiveness of chemotherapy may largely be the
      result of partial ovarian ablation produced in premenopausal patients. Based on
      this position, we propose a clinical trial that would establish the optimal
      therapy for premenopausal breast cancer. In addition, the beneficial effects of
      long-term tamoxifen as it pertains to serum lipids and bone density are
      highlighted. The use of tamoxifen maintenance in oophorectomized women might
      provide an optimal therapy for the control of breast cancer recurrence.

PMID- 8873323
TI  - Recommendations on follow-up of breast cancer patients following primary therapy.
AB  - Follow-up of breast cancer patients who have completed their primary therapy has
      not been standardized. The literature is reviewed and it is proposed that
      "minimal" follow-up with history and physical examination is the most appropriate
      procedure. Data show that more expensive imaging studies be carried out only in
      patients who are symptomatic from their disease, otherwise such an intensive
      follow-up schedule is not cost effective.

PMID- 8873324
TI  - Inflammatory breast cancer: the evolution of multimodality treatment strategies.
AB  - Inflammatory breast cancer is an aggressive subtype of invasive breast cancer.
      Early attempts to control the disease with local treatment modalities alone had a
      minimal impact on survival. More recently, multimodality treatment approaches
      that integrate systemic chemotherapy, surgery, and radiotherapy have resulted in
      improved local disease control and prolonged survival. Better systemic therapies
      need to be developed since metastatic disease develops in the majority of
      patients.

PMID- 8873325
TI  - Male breast cancer.
AB  - Male breast cancer is an uncommon malignancy, making it difficult to accurately
      define the features and optimal management of this disease. As more information
      is generated, it appears that the pathogenesis is related in large part to
      hormonal alterations but that the histologic features, biologic behavior, and
      prognosis are similar to tumors in female patients. As a result of larger studies
      based upon female patients, treatment algorithms have evolved to include
      multimodality therapy and less radical surgery. Continued research of this
      disease will continue to define improved methods of detection, prevention, and
      treatment, and, without the confounding variables of the menstrual cycle,
      menopause, and childbirth, may also provide a clearer understanding of breast
      cancer in women.

PMID- 8873326
TI  - Pregnancy and breast cancer.
AB  - Breast cancer and pregnancy are best considered as two discrete events which may
      occur either simultaneously or sequentially without any discernible biological
      interaction. There is no epidemiologic, clinical, or prognostic evidence that
      pregnancy, or its termination, will alter the natural history of breast cancer.
      Further, the existence of a pregnancy need not compromise effective breast cancer
      treatment, although the selection of modalities must consider fetal safety.
      Adjuvant radiotherapy, and thus breast conservation, is contraindicated unless it
      can be deferred until after completion of the pregnancy. Adjuvant chemotherapy is
      best delayed until after completion of the first trimester, and then, use of
      antimetabolites such as methotrexate and flourouracil should be avoided. Although
      the diagnosis of breast cancer during pregnancy may be only a biological
      coincidence, the emotional impact of this coincidence can be devastating on both
      patient and family. Informed medical care and compassionate support are both
      essential for women who simultaneously must confront the diametrically opposed
      implications and expectations of a life-giving and a life-threatening process.

PMID- 8873327
TI  - In defence of human anatomy--a commentary.

PMID- 8873328
TI  - Left subpancreatic transplexus exposure of the proximal abdominal aorta.
AB  - The authors report their experience based on the anatomical study of the celiac
      region and on the practice of abdominal multiorgan removal for transplantation.
      They particularly concentrate on the limits and the content of the celiac region
      of Luschka and particularly: -the position of the celiac axis in relation to the
      median arcuate ligament of the diaphragm, -the relations of the collateral
      branches of the abdominal aorta, -the place being taken by the celiac plexus and
      its situation in relation to the left renal v. From these elements, they describe
      an original transplexus surgical exposure of the origins of the celiac axis and
      of the superior mesenteric a. They show the importance of this approach in
      abdominal vascular surgery and during abdominal multiorgan removal in
      transplantation.

PMID- 8873329
TI  - Anatomic basis of micturition and urinary continence. Muscle systems in urinary
      bladder neck during ageing.
AB  - Dorschner et al have described the unique function and form of several different
      muscle systems of the urinary bladder neck. If these systems have different
      functional responsibilities, then the muscles must undergo different ageing
      processes, as stated in the theory of function-dependent ageing. One
      characteristic of histologic ageing is the change over time in the proportion of
      muscle cells to connective tissue, a phenomenon we have demonstrated in both the
      ciliary muscle and in the two muscle systems of the small intestine. Using an SIS
      Image Analysing System, we have now measured automatically the ratios of muscle
      cells to connective tissue in sections from several regions of the urinary
      bladder neck, taken from 50 male and 15 female cadavers. Our results confirm new
      functional explanations of the different muscle systems in the bladder neck. The
      relative volume of muscle cells in both the sphincter trigonalis m. and the
      dilator urethrae m. diminishes continuously with age. In the ejaculatorius m.,
      however, the volume of muscle cells first increases until beginning at the end of
      the third decade, it decreases until senescence. As was presumed, the proportion
      of muscle cells in the detrusor vesicae m. does not decline during the later
      decades. The volume of muscle cells and fibers in both urethral sphincter
      muscles, however, decreases with age, beginning in early childhood.

PMID- 8873330
TI  - Anatomic basis for the dorsal radial flap of the thumb: clinical applications.
AB  - The pattern of the dorsal arterial supply of the thumb was studied by the
      dissection of 25 thumbs of fresh cadavers. A constant vascular axis was found,
      originating at the radial a. and communicating at the level of the middle third
      of the proximal phalanx with the arterial palmar circuit. The constant presence
      of this vascular axis and its connection with the palmar circuit permits the
      mobilisation of a dorsal metacarpal skin flap, with a distal pedicle and a
      reversed flow, that can be used for covering dorsal and palmar losses of
      substance in the thumb.

PMID- 8873331
TI  - The artery of the atrioventricular node: an anatomic study based on 38 injection
      dissections.
AB  - The origin and course of the artery of the atrioventricular node (AAVN) was
      studied in 45 anatomic specimens by the method of injection-dissection in 38
      human hearts removed at medicolegal autopsies from black Senegalese subjects.
      Though sometimes double, the AAVN is classically solitary. Its coronary origin,
      which is always distal, occurred on the right side in the great majority of
      cases, at the level of the "U-turn of James", and on the left side at the level
      of the terminal portion of the circumflex a. At the level of Koch's triangle, its
      course is marked by a close relationship with the zone of attachment of the
      septal cusp of the right atrioventricular valve on the one hand, and with the
      orifice of the coronary sinus on the other. In cardiac surgery, respect for the
      area of Koch's triangle, the base of the interatrial septum and the region of the
      intersection of the cardiac sulci will reduce the risks of injury to the AAVN.

PMID- 8873332
TI  - Origin of the anterior spinal artery.
AB  - This investigation was designed to extend our present knowledge of the origin of
      the anterior spinal a. and is based on 80 brains of human cadavers. The anterior
      spinal a. is usually formed rostrally by the union of the anterior spinal
      branches from the intracranial segments of the vertebral aa. In this study, we
      observed three different locations of the origin of the anterior spinal a. Each
      type has different characteristics. A bilateral origin (type I) was present in 60
      specimens (75%). This type could be further subdivided according to the caliber
      of the arteries, into the following subtypes: "balanced" (type Ia 42.5%), right
      dominated (type Ib 17.5%), and left-dominated (type Ic 15%). A unilateral origin
      (type II) was found in 9 specimens (11.3%), and an origin in an intervertebral
      transverse anastomosis was demonstrated in 11 (13.8%). In all cases, the anterior
      spinal a. had an average caliber of 1.145 +/- 0.12 mm.

PMID- 8873333
TI  - Anatomic study of the tendinous rotator cuff of the shoulder.
AB  - The aim of this study was a better understanding of the role of the vascular
      supply as a pathogenic factor in rotator cuff disease. Twenty-five shoulders from
      unembalmed cadavers were studied after injection of the upper limb aa. with
      barium sulfate. The predominant arteries were the vessels of the subscapularis m.
      These branches originated from the axillary a. the anterior circumflex humeral
      a., and the posterior circumflex humeral a. The supraspinatus m. was supplied by
      the suprascapular a. but the acromial branch of the thoracoacromial a. supplied
      the tendon of the supraspinatus. The infraspinatus and teres minor tendons were
      vascularised by the ascending branches of the posterior circumflex humeral a. The
      tendon of the long head of the biceps brachii m. was supplied by a branch termed
      the "arcuate artery" and by a branch we describe derived from the brachial a. at
      the level of the latissimus dorsi tendon and travelling in a true mesotendon.
      There is a very real critical zone, with a lesser blood-flow, 1.5 cm from greater
      tubercle, situated mainly at the supraspinatus tendon. This is a convergence zone
      of the anterior and posterior circumflex humeral aa., the suprahumeral a. and the
      thoracoacromial a. The histologic studies confirmed the poor vascularity of this
      critical zone.

PMID- 8873334
TI  - The veins of the medulla oblongata: MRI cross-sectional anatomy.
AB  - Magnetic resonance imaging (MRI) has progressively become the major or even the
      only imaging procedure for displaying the vascular relationships of the brainstem
      in the context of infra-tentorial lesions. In order to assess the MR sectional
      anatomy of the bulbar vv. 40 normal patients were examined in the MR axial,
      frontal and sagittal planes after gadolinium i.v. injection. The bulbar venous
      networks were inconstantly visualised: anterior vv. (16%). posterior (3%),
      lateral (8%). The vein of the lateral recess of the fourth ventricle was constant
      in the three planes; the inferior petrosal sinus could be seen in 82% of cases.
      Their relation with the posterior fossa structures are emphasised and discussed.

PMID- 8873335
TI  - Arthrosis in the peritrapezial joints of the hand.
AB  - In the present study saddle joints of the thumb and neighboring joints of 100
      anatomic specimens are examined with regard to radiological and macroscopic
      arthrotic alterations. Comparisons of radiological and macroscopic findings
      demonstrate that early arthrotic articular alterations cannot be diagnosed
      radiologically. Almost half of the hands examined displayed arthrotic lesions in
      the saddle joint of the thumb, whereas the trapezoido-scaphoidal and trapezio
      scaphoidal joints are each affected in one third. Hands with manifest thumb
      saddle joint arthrosis are accompanied by arthrotic alterations of the joints
      between the scaphoid, trapezium and trapezoid in two-thirds of the cases. In the
      remaining radial intercarpal joints, no macroscopic evidence can be ascertained
      of arthrotic alterations. Among the processes discussed as causal factors of
      simultaneous incidence of scaphoidal and carpo-metacarpal arthroses, the
      architecture of the osseous carpus, the individual expression of the scaphoid
      bone and poly- or secondary arthrotic processes are important.

PMID- 8873336
TI  - The sacroiliac joint: anatomical study in the coronal plane and MR correlation.
AB  - The current clinical imaging technique applied to the sacroiliac joint (SIJ) is
      coronal Computed Tomography (CT). The aims of this study were: 1) to section the
      cartilage, the ligaments of the SIJ, and their relations to adjacent organs, in a
      coronal plane; 2) to correlate anatomical and magnetic resonance (MR) sections;
      3) to extend these data in vivo. A topographic dissection of a 52 year-old female
      specimen was performed to identify the various components, and spatial
      relationships of the SIJ. Another fresh frozen 50 year-old female cadaver was
      chosen on CT criteria of normality, and examined with a high resolution (HR) T1
      weighted spin echo sequence, in a plane parallel to the ventral limit of the
      first two sacral vertebrae. This cadaver was then sliced with a sliding gauge
      device (slice thickness: 5 mm, and device thickness: 1 mm). The SIJ of a 28 year
      old nulliparous volunteer, were examined in HR MR imaging, and with a faster
      sequence, for comparison with the post mortem data. The slice study was
      correlated with conventional dissection. The continuity and thickness of the
      auricular cartilage, the complex fascicles of proximal ventral and dorsal
      sacroiliac ligaments, and distant sacrotuberous and sacrospinous ligaments, were
      studied. In each plane, coronal HR MR imaging studies were correlated with
      anatomical sections. The clinical relevance of this comparison was to extend
      these data in vivo. The auricular cartilage and the ligaments of the SIJ are
      clearly analyzed by MR imaging, which could contribute to the study of
      sacroiliitis.

PMID- 8873337
TI  - Anatomical relationships and scapular attachments of the supraspinatus muscle.
AB  - Ten anatomical preparations and 15 MRI scans (Magnetic Resonance Imaging)
      performed on healthy subjects were used to define accurately the lateral
      attachments and anatomical boundaries of the supraspinatus m. Using 5 frozen
      specimens sectioned in the plane corresponding to the sagittal oblique MRI plane,
      it was possible to calculate quantitatively the ratio between the bony contours
      (O) and muscles (M) of the supraspinous fossa. This ratio was maximal (O/M = 2.4)
      for the section passing through the plane which included the coracoid process
      anteriorly and the spine of the scapula posteriorly ("Y" section). Five
      dissections on unembalmed subjects demonstrated that the postero-lateral origin
      of supraspinatus m. extended further laterally than classically described. This
      observation was confirmed in the 15 MRI subjects which showed that the
      supraspinatus m. may arise as far laterally as the "Y" section on MRI in 53% of
      cases. A quantitative evaluation of atrophy of the supraspinatus m. using MRI is
      possible with a knowledge of these two parameters.

PMID- 8873338
TI  - The clinical measurement of volumes using helical CT.
AB  - The object of this preliminary study is to evaluate the new techniques of
      measurement by helical CT which allow direct assessment of the volume of a lesion
      in clinical practice particularly by obtaining direct macroscopic anatomical
      correlation. Its primary application is anatomical, with measurement of the
      volumes of organs or anatomical structures, the clinical importance of which
      relates primarily to oncology. We present our initial results, including their
      applications and limits, before extending this study to a larger series so that
      it may be compared with other multicentre evaluations.

PMID- 8873339
TI  - A rare variant of thyroid gland vascularization.
AB  - Usually the thyroid gland obtains its blood via two paired arteries. One pair,
      the right and left superior thyroid aa., most commonly arises from the external
      carotid aa. and the second pair, the right and left inferior thyroid aa. commonly
      arises from the thyrocervical trunk of the subclavian a. In this particular case
      the right inferior thyroid a. was replaced by an artery branching off the right
      internal thoracic a.; the left inferior thyroid a. was replaced by an artery
      branching off the vertebral a. between the transverse process of the second and
      third cervical vertebrae. This finding might be explained by the suggestion that
      in the fetus there exists an anastomotic arterial chain ventral to the spinal
      column consisting of the thyrocervical trunk and the ascending cervical a. which
      itself is connected to the vertebral a.

PMID- 8873340
TI  - A variant of superficial ulnar artery.
AB  - An abnormally superficial course of the ulnar a. in the arm and forearm has long
      received the attention of anatomists and surgeons. In this study, such a case is
      reported and its importance from the viewpoint of reconstructive surgery
      stressed. The most striking findings were the origin of the superficial ulnar a.
      from the axillary a. and of the common interosseous a. from the radial a.

PMID- 8873341
TI  - The superficial peroneal nerve at the foot. Organisation, surgical applications.
AB  - The authors report the results of the dissection of the superficial peroneal
      nerves of 30 adult cadavers, from its emergence through the deep sural fascia up
      to its terminal branches. Its emergence was located, on average, 11 cm from the
      lower end of the lateral malleolus (min: 9 cm, max: 11.5 cm). The division of the
      nerve into the medial dorsal cutaneous n. and the intermediate dorsal cutaneous
      n. was found in 29 cases after its emergence from the sural fascia and before its
      passage on the proximal edge of the extensor retinaculum. The distance between
      the medial dorsal cutaneous n. and the medial malleolus was more than 2 cm. This
      nerve divided into three branches at a level varying from 5 to 20 cm in relation
      to the first interdigital space (average 9 cm). The intermediate dorsal cutaneous
      n. was found in 27 cases. It divided into two branches at a variable distance
      from the fourth interdigital space (4 to 6 cm). According to Kosinski's
      classification, we found 24 cases of type I (80%), three cases of type II (10%)
      and three cases of type IV (10%). The authors stress the numerous topographic
      variations and the multiple anatomical types.

PMID- 8873342
TI  - Determination of the position of the pelvic girdle by the method of external
      markers in the sagittal plane: a preliminary feasibility study.
AB  - The global amplitude of the movements of the trunk is the resultant of the sum of
      two components: the movements of the pelvic girdle and those of the vertebral
      segments. In order to assess the precise position of the pelvis in kinetics, we
      endeavored by the use of skin markers to determine whether reliable measurement
      points existed. The experiment showed that a line drawn from the median sacral
      crest at the level of S1 to the highest point of the iliac crest appeared
      relevant and practical for assessment of the position of the pelvic girdle in the
      sagittal plane.

PMID- 8873343
TI  - Platelet function and platelet-leukocyte adhesion in symptomatic coronary heart
      disease. Effects of intravenous magnesium.
AB  - Spontaneous P-selectin surface expression on platelets and platelet-leukocyte
      adhesion was increased in patients with symptomatic coronary heart disease (n =
      12) compared to normal controls (n = 10) (p < 0.05). ADP-induced P-selectin
      expression and platelet-leukocyte adhesion was also enhanced in the patient group
      (p < 0.05). Administration of intravenous Mg2+ significantly reduced both
      platelet surface expression of P-selectin and platelet-leukocyte adhesion ex vivo
      (p < 0.02). The effect of extracellular Mg2+ was evaluated in in vitro
      experiments. Both in whole blood and in isolated neutrophil suspension Mg2+
      inhibited platelet adhesion to neutrophils dose dependently with half maximal
      effects at 4 mM. Moreover, Mg2+ inhibited adhesion of isolated platelet membranes
      to neutrophils. We conclude that platelet function is altered in symptomatic
      coronary heart disease and can be modulated by administration of intravenous
      Mg2+.

PMID- 8873344
TI  - Hemostasis, platelet function and serotonin in acute and chronic renal failure.
AB  - A pathogenetic role for fibrin deposition and platelet activation in the kidney
      is thought to play a role in the pathogenesis of acute renal failure (ARF). Thus,
      some fibrinolytic parameters and platelet function have been studied in 17
      patients with ARF and compared to healthy volunteers and subjects with chronic
      renal failure (CRF). Since serotonin may participate in pathological processes
      resulting from platelet/vessel wall interactions, its level in the whole blood
      and plasma was also assayed. In ARF and CRF platelet aggregatory responses in
      both whole blood and in platelet rich plasma upon stimulation with various
      agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those
      obtained in healthy volunteers. Increased levels of lipoprotein (a), von
      Willebrand factor (vWF) and fibronectin were found in ARF relative to controls.
      Protein C activity was significantly lower in patients with ARF. Euglobulin clot
      lysis time was prolonged in ARF and CRF, reflecting a decreased overall
      fibrinolytic activity. Activity of tissue plasminogen activator (tPA) inhibitor
      (PAI) and PAI:Ag were higher in ARF, whereas tPA:Ag, urokinase, tPA/PAI
      complexes, thrombin-antithrombin complexes (TAT), plasmin-antiplasmin (PAP)
      complexes, fibrinogen, and F1+2 did not differ between ARF and controls. In CRF
      elevated levels of TAT, PAP, fibrinogen and prothrombin fragments F1+2 were
      found, whereas concentration of fibronectin was lowered when compared to
      controls. In both groups of renal failure patients increased levels of fibrin
      monomers and d-dimer were found relative to healthy volunteers. Whole blood
      serotonin was significantly lower, whereas plasma serotonin was significantly
      higher in patients with ARF and CRF relative to controls. Serotonin uptake and
      its release from platelets were markedly diminished in patients with ARF and CRF.
      Chronic renal failure exhibit a slightly different pattern of coagulopathies that
      acute renal failure.

PMID- 8873345
TI  - APC-resistance as measured by a Textarin time assay: comparison to the APTT-based
      method.
AB  - Protein C is a major regulatory protein critical to physiologic anticoagulation.
      When activated, it selectively degrades the activated forms of factors V and
      VIII, thereby, down-regulating blood coagulation. Using an activated partial
      thromboplastin time (APTT) assay, Dahlback et al. recently reported that some
      individuals with thrombophilia show a poor in vitro anticoagulant response to
      activated protein C (APC-Resistance). Subsequent studies identified a point
      mutation in the gene for factor V as the underlying cause of APC-Resistance. The
      incidence of APC-Resistance in patients with recurrent thromboembolic events
      approaches 50%. The APC-Resistance phenotype is also present in approximately 5%
      of normal Caucasian subjects. In an attempt to develop a more sensitive and
      specific test system, we evaluated an assay based on Textarin(Pentapharm, Basel,
      Switzerland). Textarin, a protein fraction of Pseudonaja textilis venom
      (Australian Eastern Brown Snake) activates prothrombin in the presence of
      phospholipid (PL), factor V and calcium ions. Based on Textarin's requirement for
      factor V, we developed a Textarin time assay to test for APC-Resistance. We
      evaluated this test system in normal subjects and the following patient
      populations: stable orally anticoagulated, previously diagnosed factor V Leiden,
      and therapeutically heparinized samples. We found the Textarin assay to be a
      sensitive and specific test system to identify APC-Resistance. The phenotypic
      Textarin APC-Resistance test correlated more closely with the genotypic
      abnormality of factor VR506Q than the APTT-APC-Resistance test.

PMID- 8873346
TI  - Erythrocyte membrane cholesterol/phospholipid changes and hemorheological
      modifications in familial hypercholesterolemia treated with lovastatin.
AB  - Fourteen patients with familial hypercholesterolemia treated with lovastatin (40
      mg/day) for three months were studied to find out whether the expected changes in
      plasma lipids are accompanied by modifications in the lipid composition of the
      erythrocyte membrane and whether these in turn induce changes in the rheological
      behavior of the red blood cell. Our results demonstrate the efficacy of
      lovastatin in reducing the plasma concentration of cholesterol and LDL
      cholesterol. The changes observed in the plasma lipids correlate with a
      significant decrease in the cholesterol/phospholipid ratio of the red blood cell
      membrane, from 1.19 +/- 0.19 in a basal situation to 0.92 +/- 0.23 (p < 0.01) at
      the end of treatment. These changes in the lipid composition of the cell are
      statistically related to a decrease in erythrocyte aggregability and an
      improvement in blood filterability, which means beneficial change in the
      patients' hemorheological situation.

PMID- 8873347
TI  - Evidence of a protein C-like anticoagulant system in bony fish.
AB  - Evidence is presented, confirming the presence of an anticoagulant system in the
      plasma of Atlantic salmon (Salmo salar L) and rainbow trout (Oncorhynchus mykiss
      Walbaum) (Order: Teleostei, Family: Salmonidae) that bears striking similarities
      with the protein C anticoagulant system in mammals; its vitamin K-dependence was
      documented through a warfarin feeding trial. A potent activator of this system is
      the protein C activator from the venom of the Central American Moccasin,
      Agkistrodon bilineatus. When activated, the system splits the tripeptide
      substrate glu-pro-arg-pNa, which is the substrate preferred for the in vitro
      assay of human protein C. It also prolongates the plasma activated partial
      thromboplastin time, indicating that the system is of clinical relevance. A
      temperature dependence of the plasma protein C-like activity was evident, the
      mean activity being 5- to 10-fold higher, but also more variable, in both species
      in summer and early fall, than it was in winter. There was also a species
      difference, with rainbow trout having the higher levels. In man, subnormal values
      of protein C implies an increased risk of thrombosis. Whether this applies to
      fish is not known. It is, however, a fact that microvascular thromboses are
      prevalent in farmed Atlantic salmon in winter, whereas thrombotic disease is not
      a problem in rainbow trout; in the present study plasma protein C-like activity
      was 30% (of a human reference plasma) in salmon at 4 degrees C compared to a
      level of 60% in rainbow trout. A complicating factor for the assay of protein C
      like activity in salmonid plasma, is the poor stability of the inhibitory system
      upon storage. Consequently, assays have to be done with freshly prepared citrated
      plasma.

PMID- 8873348
TI  - von Willebrand factor antigen in blood plasma of patients with urinary bladder
      carcinoma.

PMID- 8873349
TI  - Lupus anticoagulant and factor XII activity in children with prolonged PTT.

PMID- 8873350
TI  - Mixed signals in Alzheimer's disease.

PMID- 8873351
TI  - Neurofibromatosis type 2: a new mechanism of tumor suppression.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes
      primarily to CNS tumors such as schwannomas (vestibular and spinal), meningiomas,
      ependymomas and juvenile posterior lenticular opacities. Allelic losses on
      chromosome 22q first suggested the existence of a tumor suppressor on this
      autosome in accordance with Knudson's 'two hit' model. The gene was identified by
      positional cloning and found to encode a novel protein schwannomin (also known as
      merlin), with high sequence similarity to the band 4.1 family of proteins. This
      similarity suggested a new mechanism of tumor suppression since it was the first
      time a structural protein had been associated with a human tumor. Mutation
      analysis confirmed that inactivation of the NF2 gene occurred in NF2 tumors and a
      majority of sporadic schwannomas and meningiomas. Expression and functional
      studies have provided additional information on the possible involvement of this
      novel tumor suppressor in cell differentiation, embryogenesis and growth
      suppression.

PMID- 8873352
TI  - Acceleration of the effect of selected antidepressant drugs in major depression
      by 5-HT1A antagonists.
AB  - At clinically relevant doses, selective serotonin (5-HT) reuptake inhibitors
      (SSRIs) and MAO inhibitors (MAOIs) increase the extracellular concentration of 5
      HT in the midbrain raphe nuclei, thereby activating inhibitory somatodendritic 5
      HT1A autoreceptors. Consequently, the firing activity of 5-HT neurons is reduced
      and the enhancement of extracellular 5-HT concentration in forebrain is dampened.
      Overriding this feedback by using antagonists of 5-HT1A autoreceptors permits
      SSRIs to produce a marked increase of extracellular 5-HT in the forebrain. Hence,
      combined treatment with an SSRI and a 5-HT1A antagonist increases the
      extracellular concentration of 5-HT more so than the former drug alone. The
      treatment of patients with major depression using an SSRI and pindolol, a 5-HT1A/
      beta-adrenoceptor antagonist, markedly reduced the latency of the antidepressant
      response in previously untreated patients and induced a rapid improvement in
      treatment-resistant patients.

PMID- 8873353
TI  - Calcium-current facilitation in chromaffin cells.

PMID- 8873354
TI  - Simulations of receptive-field dynamics.

PMID- 8873355
TI  - GABAA-receptor subtypes.

PMID- 8873356
TI  - Is there a neural stem cell in the mammalian forebrain?
AB  - Neural precursor cells have been of interest historically as the building blocks
      of the embryonic CNS and, most recently, as substrates for restorative
      neurological approaches. The majority of previous in vitro studies of the
      regulation of neural-cell proliferation by polypeptide growth factors, and in
      vivo studies of neural lineage, argue for the presence of precursors with limited
      proliferative or lineage potential in the mammalian CNS. This is in contrast to
      renewable tissues, such as the blood or immune system, skin epithelium and
      epithelium of the small intestinal crypts, which contain specialized, self
      renewing cells known as stem cells. However, recent in vitro and in vivo studies
      from our and other laboratories lead us to conclude that neural stem cells, with
      self-renewal and multilineage potential, are present in the embryonic through to
      adult mammalian forebrain.

PMID- 8873357
TI  - Interaction of motion and color in the visual pathways.
AB  - In recent years the idea of parallel and independent processing streams for
      different visual attributes has become a guiding principle for linking the
      organization, architecture and function of the visual system. Findings concerning
      the segregation of motion and color information have been at the forefront of the
      evidence in favor of the parallel processing scheme. A number of studies have
      shown that motion perception is impaired for isoluminant stimuli, which are
      thought to isolate the color system. However, there are now many studies, the
      results of which are incompatible with the simple idea of segregated pathways. We
      propose two processing streams for motion that differ mostly in their temporal
      characteristics. Although neither of the two motion streams is color-blind, as
      was originally suggested, they differ radically in the way they process color
      information. The view that we propose provides a framework that reconciles a
      number of seemingly contradictory results. Evidence to support the new framework
      comes from psychophysical, physiological and lesion studies.

PMID- 8873358
TI  - Varieties of vision: from blind responses to conscious recognition.
AB  - Lesions in consecutive parts of the visual system cause visual deficits that
      spare increasingly complex residual functions. Patients with lesions up to and
      including primary visual cortex can show neuroendocrine, reflexive, implicit and
      forced-choice responses to visual stimulation but no conscious vision. In
      contrast, patients with lesions in higher visual cortical areas have conscious
      vision. Its lowest level is that of phenomenal vision, followed by object vision
      and recognition. These levels are dissociable. They require the integrity of
      different parts of the system.

PMID- 8873359
TI  - Wilms' tumor in adults. Review of 10 cases.
AB  - A nephroblastoma (Wilms' tumor) is very rarely found in adult patients. We report
      on 10 cases to demonstrate the diagnostic and therapeutic problems. In case of
      flank pain, large tumor mass, fast tumor growth, and young age, the possibility
      of a Wilms' tumor should be taken into consideration even in adult patients. The
      chances for a successful treatment by primary surgery with adjuvant therapy are
      favorable for the lower stages I and II. All our patients presenting with tumor
      stages I and II have survived and are free of disease since 68 months at the time
      of the study. One of 2 patients with a Wilms' tumor stage III died 8 months
      postoperatively, while the other is free of disease since 120 months. In the
      advanced stage IV no patient survived. In cases of inoperable large tumors in
      adults, the possibility of primary chemotherapy should be considered under
      certain circumstances. Rapid tumor regression may confirm the diagnosis and will
      enable salvage operation in some cases.

PMID- 8873360
TI  - Childhood urolithiasis: urological management of upper tract calculi in the era
      of extracorporeal shock-wave lithotripsy.
AB  - OBJECTIVE: To evaluate the management of urolithiasis in children since the
      development of extracorporeal shock-wave lithotripsy (ESWL). METHODS: Between
      1988 and 1994, 37 children, aged from 2 to 15 years (mean 10), with upper tract
      urolithiasis were evaluated and treated. Lithogenic metabolic disorders or
      anomalies of the urinary tract were present in 11 children (30%) Urolithiasis was
      multiple in 9 cases and bilateral in 2 cases. A total of 47 renal (30) or
      ureteral (17) stones were managed, of which 5 were partial or complete staghorn
      calculi. Initial treatment was surgery in 4 cases (1 nephrectomy, partial
      nephrectomy and 2 pyelolithotomies) and piezoelectric ESWL in 43 cases. RESULTS:
      The overall ESWL success rate was 82.2%, with auxillary endoscopic procedures in
      3 cases. ESWL failures required surgical stone removal in 5 cases, endoscopic
      ureterolithotripsy in 1 case and electrohydraulic ESWL in 1 case. Residual
      fragments after pyelolithotomies were also treated by ESWL. CONCLUSION: ESWL is
      the mainstay of treatment of childhood upper tract urolithiasis, but other
      therapeutic methods retain specific indications. Its application requires great
      vigilance and its long-term effects are uncertain. It is therefore important to
      rule out any underlying pathology and where possible to prevent further stone
      formation.

PMID- 8873361
TI  - Antisperm antibody and Klinefelter syndrome: does autoimmunity play a role in the
      pathogenesis?
AB  - Serum samples from 18 patients with Klinefelter syndrome (age range 20-22 years)
      and from a control group of 18 age-matched healthy subjects were analyzed for
      antisperm antibodies by a noncompetitive enzyme-linked immunosorbent assay. The
      antisperm antibody values were found higher in 5 patients (27.7%) than the level
      of 150 mU/100 microliters which was considered the upper level of the normal
      range (p < 0.01).

PMID- 8873362
TI  - Laparoscopic ligation of bilateral spermatic varices under epidural anesthesia.
AB  - Feasibility and safety of laparoscopic ligation of bilateral internal spermatic
      varices under epidural anesthesia were assessed in 11 patients. Another 11
      patients undergoing the same procedure under ventilation-assisted anesthesia
      served as controls. Patients in both groups belonged to the American Society of
      Anesthesia functional class I. Arterial blood analyses were obtained (1) in the
      horizontal supine position; (2) in the 15 degrees Trendelenburg position; (3) at
      15 min after carbon dioxide pneumoperitoneum insufflation, and (4) at 15 min
      after desufflation in the supine position. In the epidural anesthesia group
      arterial blood parameters and respiratory rate remained stable in the
      Trendelenburg position. After intraperitoneal insufflation of carbon dioxide for
      15 min, the arterial carbon dioxide level increased from 40.1 +/- 2.2 to 42.1 +/-
      2.6 mm Hg, the respiratory rate increased from 17.0 +/- 1.4 to 20.6 +/- 1.2/min,
      the blood pH value decreased from 7.386 +/- 0.027 to 7.355 +/- 0.034, all values
      showing statistically significant differences. These changes returned to the
      preinsufflation level 15 min after release of the pneumoperitoneum. The above
      mentioned parameters remained unchanged under the pneumoperitoneum by assisted
      ventilation in the control group. The mean time of surgery was similar in both
      groups: 82 and 90 min for the groups having general and epidural anesthesia,
      respectively. All laparoscopic procedures were accomplished successfully under
      general anesthesia. However, failure to ligate the internal spermatic varices
      occurred in 3 patients under epidural anesthesia, mainly due to patient
      intolerance to abdominal distension. The operation was continued under intubated
      general anesthesia for relaxing the abdominal muscle to provide an adequate
      working space. In 8 patients being successfully operated under epidural
      anesthesia, 5 experienced mild but tolerable abdominal distension; 2 complained
      of shoulder pain intraoperatively. Although laparoscopic ligation of internal
      spermatic varices could be accomplished in some patients under epidural
      anesthesia, it carried a high failure rate, more intraoperative morbidity, and
      significant arterial blood gas alterations. Routine ventilation-assisted
      anesthesia is suggested for therapeutic laparoscopy even for an easy procedure
      such as the ligation of the internal spermatic varices.

PMID- 8873363
TI  - Judgment of color Doppler ultrasound with respect to cavernous artery occlusion
      pressure in dynamic infusion cavernosometry when evaluating arteriogenic
      impotence.
AB  - This prospective study was designed to compare the parameters obtained by color
      Doppler ultrasound to cavernous artery occlusion pressure measured by dynamic
      pharmacoinfusion cavernosometry in evaluating arterial components of erectile
      dysfunction. Four indexes were determined as parameters of sonography to indicate
      arterial competence. Indexes 1 and 2 reflected peak systolic velocities with
      respect to the cut-off values 25 and 30 cm/s after pharmacological stimulation
      with 60 mg papaverine hydrochloride respectively. Index 3 was the percentage of
      diameter changes in cavernosal arteries which was expected to be > 75%. The sum
      of the percents of increases in diameters of both cavernosal arteries which
      should be > 200, formed index 4. The sensitivity, specificity, positive
      predictive value and accuracy rates were 76, 100, 100 and 90% for index 2. These
      values were 50, 100, 100 and 71% for index 1. Very low statistical values were
      obtained for indexes 3 and 4. Although the gold standard in the diagnosis of
      arterial impotence is pharmacoangiography, color Doppler sonography using the
      parameter peak systolic flow rate > 30 cm/s may be a reliable, easily obtained,
      noninvasive technique for evaluating arterial components of erectile dysfunction.

PMID- 8873364
TI  - Persistent bacteriuria caused by uropathogenic Escherichia coli.
AB  - The predominant strain of Escherichia coli, the most frequently associated
      causative agent of urinary tract infections (UTI), in the rectal flora of
      patients with UTI has been reported to match the strain associated with the
      etiologic agent of UTI. Since acquisition of UTI may depend on the immediate
      surrounding flora of the patient, the chromosomal DNAs of strains of E. coli
      isolated from 3 patients suffering from recurrent cystitis and asymptomatic
      bacteriuria were examined by multiple polymerase chain reaction using 6 sets of
      primers for all the known urovirulence factors and by pulsed-filed gel
      electrophoresis. Genetically identical or similar strains were continuously
      isolated from these patients and each strain carried the identical urovirulence
      factors. The findings strongly supported the previous notion that the acquisition
      of UTI is dependent upon the occurrence of the strain carrying the urovirulence
      factors in patients or in the environment.

PMID- 8873365
TI  - Immunohistochemical study of CA 19-9 and SPan-1 in cases of hydronephrosis.
AB  - Although the serum level of carbohydrate antigen (CA) 19-9 is reportedly
      increased in patients with hydronephrosis, virtually no immunohistochemical
      studies of this condition have been performed. Therefore, we examined
      immunohistochemically 11 hydronephrotic kidneys and 3 normal control kidneys
      using antibodies against CA 19-9 and SPan-1, another sialylated carbohydrate
      antigen. Immunoreactivity for CA 19-9 was seen in the transitional and tubular
      epithelia in most of the hydronephrotic kidneys (9 of the 11 cases), and also
      detected in 2 of the 3 control specimens, although there the distribution
      appeared to be limited. SPan-1 immunoreactivity showed the same trend. CA 19-9
      and SPan-1 immunoreactivity in hydronephrosis appeared to be more widely
      distributed than in controls, although its mechanism remains unclear.

PMID- 8873366
TI  - Effects of S-CMC on the cisplatin toxicity in rats.
AB  - In the present study, some toxic effects of cisplatin are evaluated in rats. It
      was also investigated whether S-carboxymethylcysteine (S-CMC), a free radical
      scavenger, protects the experimental animals from the toxic effects of cisplatin.
      The 1st, 2nd, 4th and 5th groups received physiological saline, dimethyl
      sulphoxide, and S-CMC (100 and 500 mg/kg i.p.) for 3 days, respectively. The 3rd
      group received cisplatin (5 mg/kg i.p.) 12 h before sacrifice. The 6th and 7th
      groups received S-CMC (100 and 500 mg/kg i.p., respectively); additionally, these
      groups received cisplatin (5 mg/kg i.p.) 12 h before the rats were sacrificed. 5
      mg/kg cisplatin decreased significantly serum creatinine and glutamic-oxaloacetic
      and glutamic-pyruvic transaminase levels as well as leucocyte counts. Although S
      CMC did not change the effects of cisplatin on creatinine and liver enzyme
      levels, it eliminated the effect of cisplatin on leucocyte counts. Cisplatin
      increased significantly urinary creatinine level and creatinine clearance.
      Cisplatin caused some histological changes in kidney and liver.

PMID- 8873367
TI  - An unusual presentation of adult Wilms' tumor.
AB  - Wilms' tumor (nephroblastoma), a primary renal neoplasm containing primitive
      blastema and embryonic glomerulotubular structures, is the most common malignant
      tumor of the urinary tract in children. There have been about 240 cases of adult
      Wilms' tumor reported in the world literature, however due to some differences in
      histologic findings, many cases have been reclassified as rhabdoid or clear cell
      sarcomas, both of which are recognized as separate entities. We report a case of
      an adult Wilms' tumor and discuss the clinical, radiographic and histologic
      features of this tumor.

PMID- 8873368
TI  - Cisplatin and etoposide chemotherapy in the treatment of adult Wilms' tumor.
AB  - A 64-year-old man underwent left radical nephrectomy for stage III anaplastic
      Wilms' tumor. He received adjuvant chemotherapy consisting of cisplatin and
      etoposide. Complete clinical response was achieved and maintained for 12 months.
      A systemic relapse after 1 year also responded to three more cycles of cisplatin
      and etoposide. Although cisplatin- and etoposide-based chemotherapy was not used
      as a first-line therapy in adult patients with Wilms' tumor described in the
      literature, this case demonstrates the promising activity of this combination
      also in adults with this disease entity.

PMID- 8873369
TI  - Surgical revascularization in children with renovascular hypertension.
AB  - Two boys, 11 and 10 years of age, respectively, having renovascular hypertension
      are reported. Diagnostically, captopril test and renal scintigraphy were useful
      as pharmacologic probes of the renal arterial stenosis and to determine its
      laterality, as well for examination of the operative outcome. Both children were
      rendered normotensive after renal revascularization, one by renal
      autotransplantation and the other by aortorenal bypass procedure. Renovascular
      hypertension in children is also discussed.

PMID- 8873370
TI  - Use of endorectal surface coil magnetic resonance imaging for diagnosis of a
      multicystic seminal vesicle with ipsilateral renal agenesis.
AB  - We report a symptomatic multicystic seminal vesicle with ipsilateral renal
      agenesis in a 37-year-old man. Preoperatively the diagnosis could be suggested by
      different imaging modalities, including endorectal surface coil magnetic
      resonance imaging. To our knowledge, we present the 1st case of seminal vesicle
      cyst to be evaluated by magnetic resonance imaging using a rectal coil. The value
      of different imaging modalities is discussed.

PMID- 8873371
TI  - Laparoscopic repair of traumatic intraperitoneal bladder rupture.
AB  - A case of laparoscopic management of intraperitoneal traumatic bladder rupture is
      presented. The indication for laparoscopic revision of intraperitoneal bladder
      rupture is discussed. The advantages of an automatic suturing device are
      emphasized.

PMID- 8873372
TI  - Spontaneous perforation of the ureter: endourological management with renal
      preservation.
AB  - Spontaneous perforation of the ureter proximal to an obstruction has not been
      well described in the literature. We present a rare case of spontaneous
      perforation of the ureter, proximal to a radiolucent upper ureteric stone, in a
      58-year-old diabetic female, causing a large infected urinoma and septicaemia in
      a solitary functioning kidney. The diagnosis was confirmed by computer tomography
      scan. We managed the case successfully by endourology only. The case emphasizes
      the importance of the differential diagnosis in a diabetic patient with
      obstructive uropathy.

PMID- 8873373
TI  - Ileal ureteral substitution for the treatment of bilateral ureteral obstruction
      in a patient with systemic lupus erythematosus.
AB  - Ureteral replacement by ileum is a well-described and proven technique in highly
      selective patient population. We report a case of bilateral ureteral obstruction
      with systemic lupus erythematosus to be successfully managed by total ureteral
      substitution.

PMID- 8873374
TI  - A fibroepithelial urethral polyp protruding into the base of the bladder:
      sonographic diagnosis.
AB  - A case of congenital urethral polyp in a 10-month-old boy is presented. These
      rare congenital tumors can lead to urinary retention, hematuria, urinary tract
      infections, hydronephrosis and hydroureter. Traditionally the diagnosis was based
      either on voiding cystourethrography or cystoscopy. The sonographic features of
      these polyps have only been reported in a few cases in the past. This modality is
      not infrequently the imaging procedure of choice in the work-up of children with
      signs and symptoms related to the urinary system. In the case presented herein
      the polyp was demonstrated initially by sonography as a soft tissue mass arising
      at the base of the urinary bladder. The differential diagnosis of these lesions
      is presented.

PMID- 8873375
TI  - Aggressive bone metastases in urachal carcinoma.
AB  - A 38-year-old female with urachal carcinoma showed extensive bone metastases 1
      year after wide excision of the urachal tumor, including partial cystectomy. A
      combination of radiotherapy and systemic chemotherapy was offered. Local
      radiotherapy of 8 Gy as a single fraction or 10 Gy in two fractions was delivered
      to the painful regions of the skeletal system. Multiagent chemotherapy consisting
      of methotrexate, vinblastine, Adriamycin, and cisplatin was given for three
      cycles. The patient died 28 months after the initial presentation with
      progression of the disease to pelvis and skeletal sites. The problem of
      metastatic spread after initial resection should be considered in urachal
      carcinoma, and adjuvant chemoradiotherapy should improve the outcome in this rare
      neoplasm.

PMID- 8873376
TI  - Oxalate transport and calcium oxalate renal stone disease.
AB  - Hyperoxaluria is considered to play a crucial role in calcium oxalate (CaOx)
      renal stone disease. The amount of oxalate excreted into the urine depends on
      intestinal absorption, endogenous production, renal clearance and renal tubular
      transport. Since a primary disorder has not been found so far in most CaOx stone
      formers and since oxalate is freely filtered at the glomerulus, most studies are
      presently focussed on alterations in epithelial oxalate transport pathways.
      Oxalate can be transported across an epithelium by the paracellular (passive) and
      transcellular (active) pathway. Oxalate transport across cellular membranes is
      mediated by anion-exchange transport proteins. A defect in the structure of these
      transport proteins could explain augmented transcellular oxalate transport.
      Little is known about the physiological regulation of oxalate transport. In this
      review cellular transport systems for oxalate will be summarized with special
      attention for the progress that has been made to study oxalate transport in a
      model of cultured renal tubule cells. Better understanding of the physiological
      processes that are involved in oxalate transport could yield information on the
      basis of which it might be possible to design new approaches for an effective
      treatment of CaOx stone disease.

PMID- 8873377
TI  - Interactions between calcium oxalate monohydrate crystals and Madin-Darby canine
      kidney cells: endocytosis and cell proliferation.
AB  - The present investigation was designed to study the biological responses in
      cultures of Madin-Darby canine kidney (MDCK) cells exposed to calcium oxalate
      monohydrate (COM) crystals, the most common type of urinary crystals. The
      addition of COM crystals significantly accelerated the multiplication of MDCK
      cells and significantly activated the cell viability. After exposure of MDCK
      cells to COM crystals, scanning electron microscopy revealed that some crystals
      adhered to the plasma membrane and others were endocytosed by the cell. This
      cellular uptake of crystals was time dependent from 1 to 8 h and showed a
      specificity according to crystal type. However, the endocytosis of aggregated COM
      crystals was less marked than that of non-aggregated crystals. Pre-treatment with
      each of the glycosaminoglycans (sodium pentosan polysulphate, heparin, and
      chondroitin sulphate C) produced a significant reduction of the cellular uptake
      of COM crystals, suggesting that these glycosaminoglycans may play some critical
      roles in preventing the cellular uptake of crystals. Although investigation in
      further detail is necessary, we speculate that these crystal-cell interactions,
      that is, the cellular uptake of crystals and cell proliferation, may be among the
      earliest processes in the formation of kidney stones.

PMID- 8873378
TI  - Immunocytochemical localization of Tamm-Horsfall protein in the kidneys of normal
      and nephrolithic rats.
AB  - Studies using in vitro systems have indicated that Tamm-Horsfall protein (THP)
      can interact with calcium oxalate (CaOx) crystals during kidney stone formation.
      However, information regarding the nature of its participation in this process
      remains controversial and unclear. In order to better understand the putative
      interaction of THP and crystals in vivo, we compared the localization of THP in
      normal rats and in chronic and semi-acute rat models of nephrolithiasis. In these
      rats, CaOx crystal deposits were induced in the kidneys by administering ethylene
      glycol (EG) in drinking water. The formation of CaOx mono- and dihydrate
      aggregates in the urine was confirmed by scanning electron microscopy.
      Immunohistochemical localization, as well as protein A-gold labeling at the
      ultrastructural level, demonstrated that in addition to its normal distribution,
      THP specifically associated with the renal crystal deposits. The THP-containing,
      organic matrix-like material consisted of a fine, fibrillar meshwork surrounding
      individual crystals and their aggregates. In addition, THP also appeared in the
      papilla, where it is normally absent, concurrent with the appearance of crystal
      deposits in the kidneys. These observations indicate that in nephrolithic rats
      the normal localization of THP is altered. Such an alteration may indicate an
      important physiological event related to crystal aggregation and kidney stone
      formation.

PMID- 8873379
TI  - Hamster to rat kidney transplantation: technique, functional outcome and
      complications.
AB  - Hamster to rat kidney transplantation has only recently been introduced as model
      of concordant xenografting. The kidney model offers unique possibilities for
      studying both immunological and functional aspects of xenografts as opposed to
      the widely used heterotopic heart model. This article provides a detailed
      description of surgical technique as well as data on functional outcome and
      complications. The renal artery with a small segment of the aorta is sutured end
      to-side to the abdominal aorta of the recipient, and the renal vein is
      anastomosed end-to-side to the inferior vena cava. The urinary system is
      reconstructed by bladder-to-bladder anastomosis. Xenografts will maintain close
      to normal serum-creatinine levels for 2-3 days, after which they are rejected.
      Complications occurred in 22% of xenografts. Postrenal obstruction due to severe
      hematuria or ureter stenosis was the most frequent problem encountered.

PMID- 8873380
TI  - Renal hemodynamic response to ureteral obstruction during converting enzyme
      inhibition.
AB  - Acute unilateral obstruction (UUO) of the pig kidney is associated with an
      increased secretion of intrarenally generated angiotensin II (ANG II). In order
      to clarify the importance of this intrarenal ANG II generation during acute UUO,
      ipsilateral and contralateral renal blood flow and renal secretion rate of ANG II
      were determined in pigs during continuous infusion of an angiotensin I converting
      enzyme (ACE) inhibitor. Pigs were operatively equipped with electromagnetic flow
      probes and catheters in the renal veins and aorta. Intravenous administration of
      the ACE inhibitor SQ14225 (captopril), 1 mg/kg per hour, resulted in a
      significant increase in renal blood flow in the contralateral kidney from 340 +/-
      28 ml/min to 435 +/- 36 ml/min (P < 0.01), whereas renal blood flow in the
      ipsilateral kidney was significantly reduced from 388 +/- 23 ml/min to 248 +/- 24
      ml/min, similar to the reduction in controls. Captopril reduced mean aortic blood
      pressure, renal vascular resistance consistently on both sides, and plasma
      concentrations of ANG II and aldosterone from all sample sites. Renal secretion
      rate of ANG II showed a clear tendency to be reduced from the ipsilateral kidney.
      The results suggest that in UUO a compensatory increase in renal blood flow may
      be inhibited in part due to an enhanced secretion of ANG II in the ipsilateral
      kidney. However, a captopril-mediated inhibition of bradykinin breakdown may also
      explain some of the observed changes.

PMID- 8873381
TI  - Contractile and cytoskeletal proteins in urinary bladder smooth muscle from rats
      treated with epidermal growth factor.
AB  - Systemic treatment with epidermal growth factor (EGF) induces growth of all wall
      layers in the urinary tract of pigs and rats. The present study was initiated to
      describe morphological and biochemical changes in the bladder smooth muscle from
      rats treated with EGF for 4 weeks. Eight-week-old female Wistar rats were treated
      with subcutaneous injections of vehicle (n = 16) or EGF (n = 8, 150 micrograms/kg
      per day) for 4 weeks. After EGF treatment the bladders were increased in weight
      [74.4 +/- 0.4 vs 122.1 +/- 0.5 mg, P < 0.001 (mean +/- SEM)]. Sodium dedecyl
      sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analyses of six bladders
      from each group revealed that the total amounts of actin, myosin and desmin were
      statistically significantly increased by 62%, 61% and 154%, respectively. The
      relative amounts of actin and myosin were unchanged whereas the desmin to actin
      ratio was significantly increased - as previously described in rat bladder smooth
      muscle hypertrophy. Light and electron microscopy of two bladders from each group
      revealed increased wall thickness involving all wall layers. The smooth muscle
      fibres at a midventral bladder location seemed only slightly hypertrophic-some
      degree of hyperplasia was therefore suspected. In conclusion, EGF treatment for 4
      weeks induced a net synthesis of contractile and cytoskeletal proteins in the
      urinary bladder smooth muscle.

PMID- 8873382
TI  - Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in
      urinary bladder biopsies.
AB  - Microbes may be involved in the pathogenesis of interstitial cystitis (IC).
      Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder
      and they are causative agents for hemorrhagic cystitis. We therefore studied the
      presence of adenovirus and BKV genomes in urinary bladder tissue specimens of
      patients with IC using polymerase chain reaction (PCR) and in situ hybridization
      (ISH). Controls were specimens from cases with transitional cell carcinoma of the
      bladder. Nucleic acids were extracted from paraffin sections of the bladder
      tissue for PCR. Primers detecting all adenovirus types were used. In situ
      hybridization was carried out for the paraffin sections using digoxigenin-labeled
      DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one
      to two infected cells/specimen. All the seven IC cases studied and six controls
      were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was
      also considered negative in IC cases and controls. The specimens which were
      negative in PCR tests yielded a signal with beta-globin primers, thus being
      amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic
      role in interstitial cystitis.

PMID- 8873383
TI  - The 9p21 region in bladder cancer cell lines: large homozygous deletion
      inactivate the CDKN2, CDKN2B and MTAP genes.
AB  - Homozygous and hemizygous deletions of 9p21 are the earliest and most common
      genetic alteration in bladder cancer. The identification of two cell cycle
      regulators, CDKN2 and CDKN2B, that map to the common region of deletion has
      prompted the hypothesis that they are critical tumor suppressor genes in this
      malignancy. However, controversy as to whether these genes are the only or even
      the most important target in bladder cancer oncogenesis remains. To more clearly
      determine the effect of these 9p21 alterations, we mapped the homozygous
      deletions and performed a detailed mutational and expression analysis for CDKN2,
      CDKN2B and a closely linked gene, methylthioadenoside phosphorylase (MTAP), in 16
      established bladder cancer cell lines. Nine of the 16 lines exhibit large (30 to
      > 2000 kb) homozygous deletions on 9p21. All deletions include at least one exon
      of CDKN2, eight of nine include CDKN2B, and six of nine include MTAP. MTAP
      function correlates with the genomic deletions. SSCP and sequence analysis does
      not reveal any inactivating point mutations of CDKN2 or of CDKN2B in any of the
      cell lines without homozygous deletions, and all express the CDKN2 and the CDKN2B
      mRNA as well as the encoded p16 protein. The p16 protein levels vary widely and
      are correlated with absent pRb expression. We conclude that the 9p21 deletions in
      bladder cancer usually inactivate the CDKN2. CDKN2B, and MTAP genes but that
      CDKN2 is the most common target. Other mechanisms for inactivating this gene in
      bladder cancer appear to be uncommon.

PMID- 8873384
TI  - Induratio penis plastica: effectivity of low-dose radiotherapy at different
      clinical stages.
AB  - This study describes the treatment of Peyronie's disease by means of low-dose
      radiotherapy. We treated 265 men aged 24.5-79.4 years (median = 57.7 years). No
      previous therapy had been carried out in 214 patients, and 41 patients had been
      pretreated (systemic: potassium p-aminobenzoate, vitamins a, b, e; topical:
      corticosteroids, teleradiotherapy). The disease was classified using criteria
      proposed by Alth in 1984 location, number and size of foci, hardness of
      fibromatous foci and axis deviation, potentia coeundi and pain were evaluated).
      Radiotherapy was performed by local application of a special iridium-192 moulage
      developed at our institute. In 66.4% of the monitored patient group (n = 155)
      therapy was successful. We obtained complete regression of the fibromatous foci
      in 9% (n = 14), partial remission > 50% in 29.7% (n = 46) and partial remission <
      50% in 27.7% (n = 43) of the patients. We found a significant correlation between
      hardness, size of the treated foci and therapeutic success. Eighty-three patients
      suffered from pain during penile erection before therapy, and in 61.4% (n = 51)
      of these patients the pain disappeared after treatment. Moreover, the patients
      confirmed that both loss of pain and regression of deviation related to foci
      regressions were correlated with improvement in erectile function. No serious
      side effects were observed in any of our patients.

PMID- 8873385
TI  - Economic aspects of vaccination.

PMID- 8873386
TI  - Recombinant, octavalent group A streptococcal M protein vaccine.
AB  - One of the major obstacles to the development of group A streptococcal M protein
      vaccines is the multiplicity of M serotypes expressed by these organisms. In this
      study, we have constructed a recombinant, hybrid M protein that contains type
      specific aminoterminal fragments of eight different M proteins. We show that the
      purified hybrid recombinant protein is immunogenic in rabbits and evokes
      antibodies that react with native M proteins from the respective streptococcal
      serotypes. In addition, the immune sera evoked by the octavalent protein
      opsonized six of the eight serotypes of streptococci, indicating that the
      majority of the M protein fragments contained protective epitopes that retained
      their native conformations in the hybrid protein. None of the antisera raised
      against the octavalent protein crossreacted with human heart tissue. These
      studies indicate that multivalent, hybrid M proteins may be used to elicit
      broadly protective immune responses against multiple serotypes of group A
      streptococci.

PMID- 8873387
TI  - Construction, purification and immunogenicity of antigen-antibody-LTB complexes.
AB  - An oligonucleotide, encoding a short epitope peptide tag, termed Pk, was inserted
      at the 3'-end of the gene coding B-subunit of Escherichia coli heat-labile
      enterotoxin (LTB). The presence of the Pk epitope on LTB-Pk was used to construct
      novel macromolecular assemblies comprising LTB-Pk, an anti-Pk mAb, (mAb SV5-P-k)
      and Pk-linked recombinant SIV proteins. The 1:1:1 stoichiometry of such complexes
      was ensured by binding LTB-Pk to one arm of mAb SV5-P-k and an SIV-Pk antigen to
      the other arm of the antibody. Such SIV-mAb-LTB macromolecular complexes bound to
      GM1-ganglioside in vitro, and when immunized systemically into mice were highly
      immunogenic, inducing both humoral and cell-mediated responses to the recombinant
      SIV antigens.

PMID- 8873388
TI  - Immunization of mice with recombinant L7/L12 ribosomal protein confers protection
      against Brucella abortus infection.
AB  - BALB/c mice were immunized with the recombinant Brucella abortus L7/L12 ribosomal
      protein fused to maltose binding protein (MBP). Vaccinated animals mounted a
      specific immune response to the recombinant fusion protein as demonstrated by
      immunoblot analyses. Additionally, B. abortus L7/L12 ribosomal protein conferred
      a significant degree of protection when compared to mice vaccinated with adjuvant
      alone, adjuvant plus MBP or B. abortus. These results indicate that a recombinant
      B. abortus protein, previously identified as T-cell-reactive, engendered
      protective immunity to mice against brucellosis.

PMID- 8873389
TI  - Immunization with a pneumococcal capsular polysaccharide vaccine during
      pregnancy.
AB  - The feasibility of preventing invasive pneumococcal infections during the first
      few months of life by immunization during pregnancy has been investigated. One
      hundred and fifty Gambian women were immunized with either a 23-valent
      pneumococcal polysaccharide vaccine or a meningococcal polysaccharide vaccine
      during the last trimester of pregnancy. Pregnant women showed a good antibody
      response to five of the six pneumococcal polysaccharides tested (types 1, 3, 5,
      6, 14 and 19) but not to type 6 polysaccharide. Mean cord blood/maternal blood
      IgG antibody ratios varied from 24% (type 1) to 49% (type 3) and differed
      substantially between individual mother/infant pairs. Pneumococcal antibody
      levels were higher at birth in infants of women immunized with pneumococcal
      polysaccharide vaccine than in control infants. However, these antibodies
      disappeared rapidly during the first few months of life and it is uncertain how
      much clinical protection against pneumococcal infection maternal immunization
      would have provided.

PMID- 8873390
TI  - The effects of adjuvants on CTL induction by V3:Ty-virus-like particles (V3-VLPs)
      in mice.
AB  - We have previously described the generation of HIV-1 V3-specific cytotoxic T
      lymphocytes (CTL) responses in BALB/c (H-2d) mice following immunization with Ty
      virus-like particles carrying the V3 loop of gp120 (V3-VLPs) without adjuvant. In
      this study the effects of various adjuvants on CTL induction by V3-VLPs was
      examined. Mice immunized with V3-VLPs formulated in aqueous-based adjuvants,
      Detox, gamma-inulin, galactosaminylmuramyl dipeptide and Chemivax generated V3
      specific CTL responses, although at reduced levels when compared to the no
      adjuvant group. V3-VLPs prepared in Alhydrogel, algamulin or as an oil emulsion
      in SAF-MF failed to generate V3-specific CTL responses. The mechanism whereby
      alum prevented the induction of a CTL response was investigated further.
      Immunization with V3-VLPs prepared in non-saturating doses of alum or alum plus
      EDTA primed for strong CTL responses, indicating that free VLPs do, but alum
      bound VLPs do not enter the MHC class I processing pathway of antigen-presenting
      cells (APCs). Furthermore, V3-VLPs with very low doses of alum led to an
      enhancement of the CTL response. The formulation of hybrid Ty-VLPs in oil based
      or precipitating adjuvants, therefore, inhibits access to the MHC class I
      processing pathway of APCs. The intact particulate structure of hybrid VLPs is
      therefore strictly necessary for CTL induction.

PMID- 8873391
TI  - Oral vaccination against pseudotuberculosis.
AB  - Yersinia pseudotuberculosis strain M5 (serogroup IA), isolated from the faeces of
      a mara, was of considerable virulence for mice by intravenous inoculation, but of
      low virulence by oral administration, almost always producing no more than a
      transient infection, mainly of the mesenteric lymph nodes. Oral infection of mice
      with strain M5, either with a single dose of culture per os or by the
      administration of dilute culture in drinking water, protected strikingly against
      the illness and death normally produced by oral infection with virulent strains.
      Lesions of pseudotuberculosis frequently developed in vaccinated mice as a result
      of challenge, but such lesions often became sterile. Strain M5 gave protection
      against four heterologous strains (two serogroup IA, two serogroup IB). These
      results are of interest in relation to the possible immunization of (1) feral
      animals, living free in the wild or in animal reserves, and (2) some captive wild
      species in zoological collections or laboratories.

PMID- 8873392
TI  - Immunogenicity and adverse effects of inactivated virosome versus alum-adsorbed
      hepatitis A vaccine: a randomized controlled trial.
AB  - Immunogenicity and adverse effects of a novel inactivated hepatitis A vaccine
      based on virosomes (IRIV-HAV) was compared with a standard vaccine adsorbed to
      aluminium (Al-HAV). Seronegative volunteers (n = 301) were randomly allocated to
      one injection of IRIV-HAV or to two injections of Al-HAV, followed by a booster
      injection at 12 months. Two hundred and ninety-eight (99%) completed the first
      month and 215 (71%) could be evaluated at 1 year. Geometric mean antibody
      concentrations at days 0, 14 and at 12 months were similar in the two vaccine
      groups. Lower antibody concentrations were recorded with IRIV-HAV at day 28 (P <
      0.0001) and at 13 months (P = 0.02). Seroconversion to protective antibody
      levels, however, was similar (98% at day 28, 94% at 12 months, 100% at 13
      months). Local adverse effects were reported in 17% with IRIV-HAV but in 66% with
      Al-HAV (P < 0.0001) after the initial vaccination and in 32% and 42% following
      the booster vaccination (P = 0.05). In conclusion, IRIV-HAV may provide similar
      protection but cause less local adverse effects.

PMID- 8873393
TI  - Induction of a protective immune response by mucosal vaccination with a DISC HSV
      1 vaccine.
AB  - The vaccine potential of a genetically disabled Herpes Simplex Virus Type 1 virus
      (DISC HSV-1) was investigated in the guinea pig model of intravaginal (i.vag.)
      HSV-2 infection. Three mucosal vaccination routes, i.vag., intranasal (i.n.) and
      oral, were compared for their ability to protect guinea pigs from challenge with
      wild-type HSV-2. Each was effective, particularly the i.n. route, which almost
      completely abolished primary disease. This was accompanied by significantly lower
      challenge virus titres in vaginal swabs collected from the vaccinated animals. In
      all cases, vaccination with the inactivated virus preparation provided
      substantially less protection from disease than the live DISC HSV-1 by the
      equivalent route. Antibody levels in serum and vaginal washes were measured both
      after vaccination and challenge by ELISA and neutralization tests. The highest
      titres were observed following administration of the DISC HSV-1 vaccine by the
      i.n. route. Significant increases in IgA and IgG in vaginal wash fluids were also
      found in these vaccinated animals.

PMID- 8873394
TI  - Immunogenic potential of rgp120 from African HIV-1 subtype A.
AB  - Previous studies have shown that the African strains of HIV-1 mostly cluster with
      the subtypes A, C or D based on phylogenetic analysis of the ENV nucleotide
      sequences. In the present investigation we have examined the immunogenic
      potential of full length gp120 derived from the Ugandan HIV-1 subtype A isolate,
      AUG06c, using computer-based prediction methods and a plasmid-mediated
      immunization technique. Computer-assisted analysis of the amino acid residues
      identified 15 potential B-cell epitopes in gp120 of AUG06c. Despite marked
      variation in the primary sequences, these epitopes were shown to correspond well
      to analogous sites in gp120 derived from the subtype B reference clones, MN and
      IIIBBH10. The relative positions of the epitopes indicated that E9[V3], E14[C3]
      and E15[V5] correspond to the previously defined principal neutralizing
      determinant (PND) located in the V3 loop, the CD4 binding site and gp120
      "immunodominant" region, respectively. Intramuscular inoculation of BALB/c mice
      with the ENV clones from AUG06c or from the subtype C clone, CUG045 elicited
      antibodies which react with the homologous but not with the heterologous PND
      peptide in ELISA. However, cocktail inoculation with the ENV plasmids from AUG06c
      and CUG045 elicited antibodies which reacted with both peptides. Antibody
      response to the other predicted epitopes of AUG06c was not as strong as the
      response to the PND peptide. The response of the mice to DNA-mediated
      immunization was further tested in a proliferation assay. Spleen cells derived
      from the immunized mice exhibited a strong proliferative response to homologous
      and heterologous PND peptides in [3H]thymidine incorporation assay. DNA-mediated
      immunization with rgp120 of AUG06c appears to elicit cellular immune response of
      relatively broad specificity.

PMID- 8873395
TI  - Production, characterization and control of a Neisseria meningitidis hexavalent
      class 1 outer membrane protein containing vesicle vaccine.
AB  - An experimental serogroup B meningococcal vaccine was prepared from two
      genetically engineered strains; each expressing three different class 1 outer
      membrane proteins (OMPs) (PorA). The two strains expressed the subtypes
      P1.7,16;P1.5,2;P1.19,15 and P1.5c,10;P1.12,13;P1.7h,4, respectively. Outer
      membrane vesicles (OMV) were prepared from these strains by deoxycholate
      extraction, mixed with aluminiumphosphate as adjuvant and formulated to final
      vaccines. The class 1 OMPs represent ca 90% of the protein in the vaccine. The
      vaccine was found safe for human use and induced a bactericidal immune response
      in mice against five of the six wild type strains, which served as donors for the
      various por A genes.

PMID- 8873397
TI  - The challenge of controlling mastitis.

PMID- 8873396
TI  - Phase I clinical trial with a hexavalent PorA containing meningococcal outer
      membrane vesicle vaccine.
AB  - A meningococcal outer membrane vesicle (OMV) vaccine was prepared from two
      production strains designed to express three serosubtype-specific class 1 outer
      membrane proteins or PorA. The resulting hexavalent PorA OMV vaccine contained
      the serosubtypes P1.7,16; P1.5,2; P1.19,15; P1.7h,4; P1.5c,10; P1.12,13 and were
      used to immunize adult volunteers. A single immunization with two dosages, 7.5
      and 15 micrograms of the individual PorAs, was studied. The vaccine was
      considered safe for further use. Approximately half of the volunteers
      demonstrated a fourfold increase in bactericidal antibody activity against six
      test strains expressing the specific PorAs when given the higher dosage. This
      bactericidal activity was found to be directed against PorA.

PMID- 8873398
TI  - Cardiopulmonary effects of desflurane in ponies, after induction of anaesthesia
      with xylazine and ketamine.
AB  - Cardiopulmonary parameters were measured in 12 ponies (small horses) before
      anaesthesia and, following induction with xylazine and ketamine, during
      maintenance of anaesthesia with desflurane. In six of the ponies (group A)
      anaesthesia was maintained for three hours with desflurane at an end-tidal
      concentration of 7.4 per cent. In the other six ponies (group B), anaesthesia was
      maintained in the same way for one hour and then the effects of end-tidal
      desflurane concentrations of 7.4 per cent and 9.6 per cent with and without
      artificial ventilation were investigated. In group A ponies the arterial blood
      pressure and the systemic vascular resistance index (SVRI) decreased
      significantly during the first 45 minutes of anaesthesia but recovered with time.
      The cardiac index and heart rates were unchanged throughout the measurement
      period but arterial carbon dioxide tensions increased significantly. In group B
      ponies, with either mode of ventilation, increasing desflurane concentration
      resulted in decreases in arterial blood pressure, cardiac index and mixed venous
      oxygen tension, although the changes were not always statistically significant.
      There were marked individual differences in the cardiovascular responses to the
      high desflurane concentrations, the minimum mean arterial blood pressure ranging
      from 35 to 62 mm Hg, and the cardiac index from 23 to 50 ml/kg/min. The study
      concludes that during maintenance of anaesthesia with end tidal concentrations of
      desflurane of 7.4 per cent, cardiac index is well maintained and the initial fall
      in arterial blood pressures results from a fall in SVRI. However, increasing the
      concentration of desflurane causes a fall in blood pressure due to cardiac
      depression.

PMID- 8873399
TI  - Tylosin in the treatment of canine superficial pyoderma.
AB  - Thirty dogs with superficial pyoderma were treated orally with tylosin at a dose
      of 20 mg/kg twice daily for three weeks. Staphylococcus intermedius was recovered
      from 21 (70 per cent) of the dogs. Twenty-two of the dogs were free of clinical
      signs after three weeks of treatment and two dogs responded to a further two
      weeks of treatment, giving a total response rate of 80 per cent. Five cases (16.6
      per cent) failed to respond and three of these subsequently responded to other
      antibacterial treatment. One dog suffered transient gastritis after the doses of
      tylosin and subsequently responded to a different antibacterial agent.

PMID- 8873401
TI  - Compatibility of the programmed use of doramectin with lungworm vaccination in
      calves.

PMID- 8873400
TI  - Norgestomet implants, plasma progesterone concentrations and embryo transfer
      pregnancy rates in cattle.
AB  - A study was undertaken to test the hypothesis that supplementation with exogenous
      progestagen at the time of embryo transfer would enhance pregnancy rates in
      recipients. Two-hundred-and-seventy-two oestrus-synchronised crossbred heifer and
      cow recipients received 200 grade 1 and 72 grade 2 Simmental embryos transferred
      non-surgically. Heparinised blood samples were taken on day 6 and day 7 (oestrus
      = day 0) for the assessment of the endogenous plasma progesterone concentration.
      Half the recipients received an ear implant impregnated with 3 mg norgestomet on
      the day of embryo transfer. The pregnancy rates were 51.9 and 49.6 per cent for
      the norgestomet-treated and control groups, respectively. The pregnancy rate for
      grade 1 embryos was 56.0 per cent and for grade 2 embryos 36.1 per cent (P <
      0.01). The breed of recipient, weekday of transfer, operator and condition score
      had no effect on pregnancy rate. The maiden heifers had a higher pregnancy rate
      (54.2 per cent) than the cows (46.2 per cent). The mean plasma progesterone
      concentrations of the pregnant and non-pregnant groups on day 6 were 6.7 ng/ml
      and 6.6 ng/ml, respectively, and 7.6 ng/ml in both groups on day 7.

PMID- 8873402
TI  - Ocular disease associated with Rhabditis orbitalis nematodes in a common dormouse
      (Muscardinus avellanarius).

PMID- 8873403
TI  - BVA/Kennel Club hip dysplasia scheme.

PMID- 8873404
TI  - Acute encephalopathy in a horse: toxic differentials.

PMID- 8873405
TI  - Euthanasia of large animals.

PMID- 8873406
TI  - Helicobacter pylori and stomach ulcers.

PMID- 8873407
TI  - Helicobacter pylori and stomach ulcers.

PMID- 8873408
TI  - Single-strand conformation polymorphism analysis of RT-PCR products of UK
      isolates of barley yellow mosaic virus.
AB  - Single-strand conformation polymorphism (SSCP) analysis of the bipartite genomes
      of several UK isolates of barley yellow mosaic virus (Ba YMV) was done using
      fragments of cDNA amplified by RT-PCR. Isolates differed in their SSCP patterns
      in several regions, but in no case was the pattern able to distinguish between
      common and resistance-breaking strains. In regions where the nucleotide sequences
      of UK isolates had been determined, there was no simple relationship between
      numbers of nucleotide differences and SSCP patterns: differences of only 2 or 3
      nucleotides (nt) gave different SSCP patterns, whereas differences of as many as
      29 nt did not. Although SSCP analysis has some potential as a rapid and sensitive
      tool for distinguishing virus isolates, differences detected do not necessarily
      relate to biological properties and the results are highly dependent on gel
      conditions.

PMID- 8873409
TI  - Expression of ubiquitin, actin, and actin-like genes in African swine fever virus
      infected cells.
AB  - Northern blot hybridisation was used to study the accumulation of specific
      cellular mRNAs (ubiquitin and actin) in Vero cells infected with African swine
      fever virus (ASFV). ASFV modulates the cytoplasmic levels of ubiquitin and actin
      mRNAs throughout infection. Before viral DNA replication, degradation of
      ubiquitin mRNAs is dependent on de novo protein synthesis, since treatment with
      cycloheximide (CH) allowed the accumulation of ubiquitin mRNAs, while treatment
      with cytosine arabinoside (araC) induced a reduction in ubiquitin transcripts.
      Nevertheless, viral DNA replication is essential to the final increase observed
      in ubiquitin mRNA degradation. Furthermore, ubiquitin transcription seems to be
      tightly related to viral gene transcription, since before viral DNA replication
      ubiquitin and viral transcripts accumulate at opposite rates. Concerning actin
      transcription, the first step in actin mRNA degradation does not depend on de
      novo protein synthesis, since treatment with CH induced a reduction in actin
      mRNA. The second step in actin mRNA degradation, similarly to ubiquitin, depends
      on viral DNA replication. Finally, in the present study it has also been shown
      that ASFV codifies for actin-like genes. This is the first report of a virus
      encoding an actin-like gene.

PMID- 8873410
TI  - Mutations in the nonconserved noncoding sequences of the influenza A virus
      segments affect viral vRNA formation.
AB  - Influenza A virus replication and packaging is mediated by cis-acting signals,
      which are located at the 3' and the 5' end of the viral segments. The terminal
      residues can be divided into conserved and nonconserved residues. We have
      constructed a mutant influenza A/WSN/33 virus, which contains multiple mutations
      in the nonconserved residues of the neuraminidase (NA) segment. This virus shows
      a segment-specific reduction of the genomic RNA content in the infected cell and
      in the progeny virus. Further mutants and revertant viruses revealed that it was
      not possible to define specific residues, which were responsible for the
      reduction of the NA-specific RNA. Thus, it appears that an efficient vRNA
      formation is dependent on the synergistic effect of the terminal sequences.

PMID- 8873411
TI  - Sequence characterization of human Borna disease virus.
AB  - Borna disease virus (BDV) causes a central nervous system disease in several
      vertebrate animal species, which is manifest by behavioral abnormalities.
      Seroepidemiologic data suggest that BDV might infect humans, possibly being
      associated with certain mental disorders. This is further supported by the
      detection of both BDV-specific antigens and RNA sequences in peripheral blood
      mononuclear cells (PBMCs) of psychiatric patients. For the first time the
      sequence characterization of human BDV is documented here. BDV was recovered by
      co-cultivation techniques from the PBMCs of three hospitalized psychiatric
      patients. BDV was unequivocally identified based on sequence identification of
      BDV open reading frames (ORFs) p24, p16 and p56, as well as of the predicted
      catalytic domain of the BDV L polymerase. Each human BDV isolate had an unique
      sequence, but they displayed a high degree of sequence conservation with respect
      of BDV isolates from naturally infected animals of different species.

PMID- 8873412
TI  - A highly attenuated strain of Japanese encephalitis virus induces a protective
      immune response in mice.
AB  - A pair of virulent (RP-9) and attenuated (RP-2ms) mutants of Japanese
      encephalitis virus (JEV) were generated from a Taiwanese isolate NT109. The
      mutants differed in several aspects in vitro and in vivo. RP-2ms exhibited
      smaller plaque than RP-9 on BHK-21 cells, and when intracerebrally injected, RP
      2ms was much less neurovirulent than RP-9. As peripherally inoculated, RP-2ms
      lost neuroinvasiveness while RP-9 penetrated blood-brain barrier, replicated in
      mouse brain, and killed all the mice. Single RP-2ms immunization completely
      protected C3H and ICR mice from a lethal challenge with RP-9; the sera from such
      mice contained antibodies against JEV envelope and nonstructural 1 proteins,
      indicating RP-2ms had replicated in the mice Neutralizing activity against NT109
      in such sera was further demonstrated by plaque reduction neutralization test. In
      addition, significant lymphoproliferation was detected in spleen cells from the
      RP-2ms-immunized mice, and cytotoxic activity in these cells specific for the MHC
      matched, JEV-infected cells, but not mock cells, was also observed. Altogether,
      these results demonstrate that RP-2ms, a highly attenuated JEV strain, can induce
      a protective immunity in mice.

PMID- 8873413
TI  - Transforming activities of human papillomavirus type 59 E5, E6 and E7 open
      reading frames in mouse C127 cells.
AB  - The DNA sequence from a human papillomavirus type 59 (HPV 59) has been recently
      determined. The HPV 59 genome consists of 7896 nucleotides (nt). A comparative
      analysis of this sequence with the sequences of other HPVs revealed the closest
      homology to HPV 18 (71%). To test the transforming activities of HPV 59 DNA and
      its gene products, several plasmids expressing HPV 59 open reading frames (ORF)
      were constructed. The E5, E6, and E7 ORFs of HPV 59 were inserted into pRc/CMV
      vector containing a promoter of cytomegalovirus to test the transforming
      activities of these ORFs. When these DNAs were transfected into mouse C127 cells,
      all three ORFs were independently able to transform C127 cells in the presence of
      G418, although the full length HPV 59 DNAs failed to induce the focus-formation.
      The E7 ORF showed the strongest transforming activity and the E5 ORF exhibited
      the weakest transforming activity. Cell lines transformed by E5, E6, and E7 ORFs
      were established and they grew anchorage-independently. The presence of HPV 59
      ORF DNA was confirmed by polymerase chain reaction (PCR) and Southern blot
      analysis in HPV 59 ORFs-transformed cell lines.

PMID- 8873414
TI  - Efficient induction of persistent and prenatal parvovirus infection in rats.
AB  - Parvoviruses are prevalent and disruptive infectious agents of laboratory rats.
      Risks to rat-based research from infection are increased by the persistence of
      virus in immune rats and by prenatal transmission of infection. The mechanisms
      leading to viral persistence and prenatal infection are poorly understood and
      have been difficult to study for lack of reliable and humane induction methods.
      We report here protocols for inducing persistent and prenatal infection without
      causing clinical disease using the UMass strain of rat virus (RV), a common rat
      parvovirus. Infant rats inoculated by the oronasal route at 6 days of age had
      greater than 90% prevalence of persistent infection. RV-UMass also induced
      intrauterine infection in pregnant rats inoculated by the oronasal route.
      Inoculation of dams at gestation day 9 frequently caused severe disease in the
      fetuses whereas inoculation at gestation day 12 caused primarily asymptomatic
      fetal infection that persisted post partum RV-UMass infection facilitates study
      of parvoviralhost interactions that are relevant to laboratory rats and which
      also may improve understanding of persistent and prenatal human parvovirus
      infection.

PMID- 8873415
TI  - Role of the blood transfusion service in tissue banking.
AB  - Tissue transplantation and banking are rapidly growing services throughout the
      world reflecting the widening availability of transplantable cadaver tissue and
      the mounting clinical indications particularly in orthopaedic, plastic and
      cardiovascular surgery. In the US tissue banking is more established, yet
      continues to show a rapid growth profile. In the UK it is currently organised in
      a variety of different ways and by a number of different organisations. The risks
      of disease transmission by tissue transplantation are similar to those for blood
      transfusion and the majority of tissues are grafted during procedures that are
      not life saving. The danger of disease transmission has resulted in the
      introduction of legislation in the US which allows the FDA to inspect tissue
      banks and to recall and destroy tissues. In the UK, there is currently no
      regulation or inspection of tissue banks to demonstrate that donor selection,
      tissue processing and tracking are conducted to acceptable standards. Blood
      transfusion services in the UK, US, New Zealand, Australia and possibly other
      countries have extended their roles to include organ and tissue donation to
      varying degrees, with the collection, processing and distribution of bone and
      tendon allografts most commonly undertaken. They have readily available special
      capabilities and experience with an established infrastructure, compliant with
      Good Manufacturing Practice, placing them in an ideal position to provide this
      service safely and cost-effectively.

PMID- 8873416
TI  - Influence of the red blood cell preparation method on the efficacy of a leukocyte
      reduction filter.
AB  - The performance of a leukocyte reduction bedside filter with different types of
      RBC concentrates was analyzed. Three types of RBCs were prepared: buffycoat
      depleted RBCs suspended in saline-adenine-glucose-mannitol (SAGM)-additive
      solution (BC-RBCs; n = 20), RBCs suspended in SAGM-additive solution without
      buffy coat removal (SAGM-RBCs; n = 20), and RBCs drawn in CPDA-I conservative
      solution and processed for component preparation by the platelet-rich plasma
      method (CPDA-RBCs; n = 20). The units were filtered within 8 h of collection. One
      filter was used for every 2 units. High numbers of residual WBCs were found even
      in the units filtered first. Filtration of CPDA-RBCs resulted in a higher
      residual WBC content than SAGM-RBCs or BC-RBCs (p = 0.0032 and p = 0.0002,
      respectively). The filter performance strikingly decreased when the WBC load per
      filter exceeded 4 x 10(9) or the platelet load was less than 100 x 10(9). We
      conclude that filter performance varies with the WBC and platelet content of the
      RBC concentrates. Under the experimental conditions assayed in this study CPDA
      RBCs are the least appropriate ones to be used for bedside leukocyte reduction.

PMID- 8873417
TI  - Procoagulant effect of incompatible platelet transfusions in alloimmunized
      refractory patients.
AB  - The clinical effectiveness of platelet transfusion in refractory patients is
      still a subject of debate. We have evaluated the possible hemostatic effect of
      platelet transfusion in 16 alloimmunized thrombocytopenic patients whose platelet
      counts were less than 20,000/microliters. Platelet concentrates were always
      obtained by apheresis procedures from incompatible donors. The posttransfusion
      platelet recovery was greater than 15% only in 3 cases. In the first 6 patients,
      measurements of bleeding time performed immediately before transfusion were in
      all cases longer than 30 min and did not change significantly 10 and 60 min after
      platelet transfusions. In all patients, ex vivo perfusion experiments with
      Baumgartner's platelet adhesion model, using native nonanticoagulated blood, were
      performed immediately before and 10 and 60 min after transfusion. No difference
      in platelet deposition onto the subendothelial surface was observed after
      platelet transfusion. Unexpectedly, the deposition of fibrin on the
      subendothelial surface was statistically augmented in the posttransfusion
      studies. Quantification of thrombin-antithrombin complexes (TAT) in plasma showed
      statistically significant elevations (p < 0.01) in the posttransfusion samples
      (31.9 +/- 12.6 vs. baseline 5.8 +/- 1.7 ng/ml), not justified by TAT levels in
      the transfused material (2.3 +/- 0.17 ng/ml). Transfusion of incompatible
      platelets to refractory patients may activate coagulation mechanisms in the
      absence of an increase in peripheral platelet count.

PMID- 8873418
TI  - Estimation of the progenitor cell yield in a leukapheresis product by previous
      measurement of CD34+ cells in the peripheral blood.
AB  - To assess whether measurement of CD34+ cells in the peripheral blood allows one
      to estimate the progenitor cell yields of subsequent leukapheresis procedures,
      733 corresponding blood and leukapheresis samples were analyzed. Peripheral blood
      progenitor cells of cancer patients were mobilized with hematopoietic growth
      factors alone or postchemotherapy, and harvested processing 10 liters of blood
      for each leukapheresis product. The CD34+ cell count (CD34+ cells/microliter
      blood) correlated most closely with the progenitor cell yield in the
      corresponding leukapheresis product (CD34+ cells/kg bodyweight, r = 0.80), while
      the proportion of circulating CD34+ cells to the white blood and mononuclear
      cells predicted the yield less reliably (r = 0.74 and r = 0.60). The CD34+ cell
      yield was independent of the white blood count (r = 0.04), whereas a weak
      correlation was found between the mononuclear cell count and the number of CD34+
      cells/kg collected (r = 0.42). It was unlikely to obtain the threshold quantity
      of 2.5 x 10(6) CD34+ cells/kg required for rapid engraftment when counts below 10
      CD34+ cells/microliter blood were detected. At levels between 10 and 30 CD34+
      cells/microliter sufficient autografts could be harvested, whereas 30-100 CD34+
      cells/microliter were required to achieve this by a single leukapheresis. A
      surplus of CD34+ cells was likely above 100 CD34+ cells/microliter which could be
      useful for progenitor cell enrichment techniques. The correlation between the
      CD34+ cell count and progenitor cell yield was independent of the mobilizing
      regimen and whether leukaphereses had been performed previously. In conclusion,
      the number of CD34+ cells/microliter blood allows a reliable prediction of the
      CD34+ progenitor cell yield in subsequent leukapheresis procedures. However, rare
      cases of unexpectedly sufficient progenitor cell yields may be observed even at
      CD34+ cell levels below detection limit.

PMID- 8873419
TI  - Stability of blood coagulation factors and inhibitors in blood drawn into half
      strength citrate anticoagulant.
AB  - Drawing of blood into a citrate-phosphate-dextrose (CPD) solution with a reduced
      citrate concentration has been shown to improve the maintenance of coagulation
      factor VIII (F VIII) in plasma and to give possibilities to improve erythrocyte
      preservation. We studied the quality of plasma obtained from whole blood drawn
      under continuous mixing into CPD in which the citrate concentration was reduced
      by 50% (0.5CPD). The blood was stored at room temperature for 8 h before
      component preparation. We confirmed improved stability of F VIII by 0.5CPD. We
      found no clinically significant changes in inhibitors to the coagulation and
      kallikrein systems, and no signs of activation of these systems, during the 8
      hour holding time. In control blood drawn into CPD, F VIII and coagulation factor
      IX decreased by 0.09 IU/ml (8%) and 0.07 U/ml (7%), respectively, otherwise we
      found no significant differences between 0.5CPD plasma and CPD plasma.

PMID- 8873420
TI  - Maternal-fetal hemorrhage: a reappraisal.
AB  - PURPOSE: To determine the frequency of maternal-fetal hemorrhage at or above 1
      microliter of maternal whole blood. METHODS: Seventy-three mothers whose red
      blood cells bore an Rh antigen (Rh D, Rh c, Rh E) that was absent on red blood
      cells of their newborns were identified and a new cytological method, the
      Kleihauerimmunogold-silver-staining technique, was applied on the blood of their
      neonates to detect and quantify maternal red blood cells. Stringent precautions
      were taken to avoid contaminations of neonatal blood samples by adult red blood
      cells. RESULTS: Maternal red blood cells were present in 3 newborns, a frequency
      of 4% (95% Cl: 1-11%), and the estimated volumes of hemorrhage were 0.8, 1.5, and
      101 microliters of maternal whole blood. No obstetric factor was clearly
      associated in this limited study with the occurrence of maternal-fetal
      hemorrhage. CONCLUSIONS: Mother-to-fetus microtransfusion greater than 1
      microliter is infrequent at or near delivery, and it may be observed after an
      uncomplicated pregnancy and vaginal delivery.

PMID- 8873421
TI  - Haemolytic disease of the newborn due to anti-G.
AB  - Mrs P. presented at 13 weeks of gestation with apparent anti-C+D. At week 34,
      with antibody levels of 168 IU/ml, a D-negative (r'r) baby was delivered with a
      strongly positive DAT and an Hb of 3.0 g/dl. Anti-G in maternal serum was
      isolated by adsorption and elution from R2R2 cells and shown, using flow
      cytometric and chemiluminescence assays, to sensitize r'r cells at levels of cell
      bound IgG consistent with fetal haemolysis. In an analysis of 28 sera from
      alloimmunized women with over 5 IU/ml anti-C+D, 2 sera were shown to contain
      levels of anti-G consistent with moderate or severe haemolytic disease of the
      newborn (HDN). Thus HDN due to anti-G may not be rare. An analysis of 187,037
      blood donors in the south-west of England showed the r' gene frequency to be
      0.005897 suggesting that approximately 2.9% of matings of rr women with D
      negative fathers can produce an r'r baby. These findings highlight the need for
      the continuous non-invasive monitoring of D-negative fetuses of women with
      apparent anti-C+D.

PMID- 8873422
TI  - Evidence for a new type of O allele at the ABO locus, due to a combination of the
      A2 nucleotide deletion and the Ael nucleotide insertion.
AB  - Using a recently introduced multiplex polymerase chain reaction and restriction
      fragment length polymorphism ABO genotype screening method we have found an
      anomalous ABO genotype (A2O1variant) not correlating with the serological
      phenotype (blood group O). The blood group was confirmed by absorption/elution
      and detection of blood group substances in saliva. Sequencing of exons 6 and 7 in
      the ABO genes of the propositus indicated an A2 gene (C467T and C1060-)
      apparently inactivated by the same single nucleotide insertion recently reported
      in individuals with the ABO subgroup Ael. Investigation of relatives confirmed
      the inheritance of this new inactive hybrid allele.

PMID- 8873423
TI  - The low-incidence blood group antigen, Wda, is associated with the substitution
      Val557-->Met in human erythrocyte band 3 (AE1).
AB  - The Waldner blood group antigen (Wda) was first identified in members of a
      Hutterite kindred. Evidence that the gene governing the Waldner polymorphism is
      located on chromosome 17, and the observation that the antigen is inactivated by
      chymotrypsin prompted the investigation of a possible association between Wda and
      band 3. Single Stranded Conformational Polymorphism (SSCP) analysis and DNA
      sequence analysis of the AE1 gene, from subjects of known Waldner phenotypes,
      showed a heterozygous mutation leading to the substitution Val557-->Met in the
      presumptive Wd(a+) heterozygotes. Therefore the Wda blood group antigen is
      associated with the presence of Met557 on band 3. the Waldner antigen has been
      assigned to the Diego blood group system with the International Society of Blood
      Transfusion number D15.

PMID- 8873424
TI  - Rapid typing for human platelet antigen systems-1, -2, -3 and -5 by PCR
      amplification with sequence-specific primers.
AB  - Typing for human platelet antigens (HPA) is useful in a variety of clinical
      situations. We developed a method for genotyping for HPA-1, -2, -3 and -5 by
      means of the PCR amplification with sequence-specific primers (PCR-SSP)
      technique. Primer sets were designed to allow PCR amplification for all systems
      using the same assay conditions. Specificity and sensitivity of the method were
      assessed in a blind quality control study (n = 112). In 111 cases, results
      obtained by PCR-SSP were identical as compared with PCR-restriction fragment
      length polymorphism technique. One discrepancy was found to be due to a typing
      error in the data sheet. The results of the PCR-SSP technique were available
      within 3 h. We conclude that genotyping based on PCR-SSP enables rapid typing for
      HPA systems, which makes this technique feasible in most clinical settings where
      urgent HPA typing is required.

PMID- 8873425
TI  - Hepatitis A transmission by factor IX concentrates.
AB  - Factor IX concentrates unlike factor VIII concentrates have not to date been
      associated with the transmission of hepatitis A virus (HAV). A retrospective
      study by reverse transcriptase polymerase chain reaction on a batch of factor IX
      concentrate used to treat two haemophilia B patients who developed jaundice and
      IgM anti-HAV antibodies within 50 days of factor IX administration in 1985
      revealed the presence of HAV RNA. These findings indicate that factor IX
      concentrates can transmit HAV and that appropriate viral inactivation steps to
      inactivate nonenveloped viruses as well as enveloped viruses are necessary to
      ensure the safety of factor IX concentrates.

PMID- 8873426
TI  - Removal of parvovirus and hepatitis A virus by metal chelate affinity
      chromatography during the preparation of Replenine: a high-purity factor IX
      concentrate.

PMID- 8873427
TI  - Provision of random-donor platelets (HPA-1a positive) in neonatal alloimmune
      thrombocytopenia due to anti HPA-1a alloantibodies.

PMID- 8873428
TI  - The use of DNA typing for human platelet-specific antigens in the daily routine:
      a case report.

PMID- 8873429
TI  - Anti-D testing in intravenous immunoglobulins: shouldn't it be considered.

PMID- 8873430
TI  - Fractal tumours: their real and virtual images.
AB  - Autonomous and uncoordinated proliferation of epithelia leads to various well
      known growth patterns such as expansive (cauliflower-like), radiating
      infiltrative, polycyclic, and roundish-ovoid figures. All attempts to describe
      such natural growth patterns graphically by Euclidean geometry have failed and
      remain no more than works of art. However, fractal geometry is a new tool for the
      characterization of irregularly-shaped and complex figures. Moreover, behind a
      fractal structure there is a basic power-law which provides the opportunity to
      simulate these forms artificially. A prerequisite for achieving this goal of
      simulating tumour growth by computer is to establish whether typical tumour
      growth patterns are fractal. Hence, an investigation was undertaken of 20 tumours
      (malignant, metastases or benign) exhibiting the above-mentioned typical
      patterns. If tumour outlines are fractal they have to possess a fractal non
      integer dimension which significantly exceeds the integer Euclidean dimension.
      The fractal dimension of tumour outlines was determined using the box-counting
      method. Almost all tumours presented a fractal dimension and virtual tumour
      images were created by utilizing available fractal software. In conclusion, the
      determination of the fractal dimension of solid neoplasms may be an additional
      morphometric parameter for growth assessment and it probably provides further
      opportunity to simulate cancer growth and infiltration by computer animation.

PMID- 8873431
TI  - Riluzole and ALS therapy.
AB  - Amyotrophic lateral sclerosis (ALS) is a severe neurological disorder clinically
      characterized by progressive muscle weakness, amyotrophy, fasciculations and
      signs of corticospinal tract deficits. The cause is unknown but several
      hypotheses are currently proposed. In familial forms of ALS, a mutation of the Cu
      Zn superoxide dismutase gene was reported in some patients. Autoimmunity and
      neurofilament dysfunction were also observed. The last hypothesis is linked to
      excitotoxicity. This cellular phenomenon is associated with the overstimulation
      of glutamate post-synaptic receptors, leading to neuronal degeneration. Abnormal
      glutamate metabolism was also discovered in ALS patients. In these conditions,
      riluzole, a pharmacological agent that reduces glutamate release from nerve
      terminals, was administered to ALS patients. Riluzole is an anti-convulsant and a
      neuroprotective agent and specifically blocks sodium channels in their
      inactivated states. In a recent double blind placebo controlled study, riluzole
      was given to 77 patients (placebo 78 patients). After 1 year of treatment 58% of
      the placebo-treated patients were still alive compared to 74% of patients treated
      with riluzole. The prolonged survival was significant in the overall population
      and in the bulbar-onset group.

PMID- 8873432
TI  - Renal transplantation is well established as the preferred form of replacement
      therapy for most patients with endstage renal disease.

PMID- 8873435
TI  - Contemporary criteria for cadaveric organ donation in renal transplantation: the
      need for better selection parameters.
AB  - A major problem facing transplantation is the disparity between the availability
      of cadaver donors and the number of recipients awaiting transplantation. Efforts
      to deal with this issue have involved the use of "marginal donors." Results
      obtained using these organs have often been significantly worse at 1 and 3 years
      of follow-up. The problem of how to select and utilize these donors is of
      critical importance to both patients and society. Current criteria available for
      assessing cadaver donors are based on ideal donors. Although these appear
      adequate for predicting the results for the ideal donor, they are not adequate
      for assessing results for marginal donors. New criteria are of critical
      importance for better utilization of these organs. The purpose of this review is
      to examine the current criteria for ideal and marginal donors, review the
      critical issues to be clarified, and discuss options for improvement results in
      the future.

PMID- 8873433
TI  - Kidney transplantation in highly sensitized patients: reappraisal of etiology,
      evaluation, and management protocols.
AB  - Transplant recipient sensitization to major histocompatibility complex (MHC)
      antigens is a major problem in clinical organ transplantation in terms of both
      magnitude and implication. Highly sensitized patients (HSPs) waiting for renal
      transplantation constitute a high-risk group with difficult management problems.
      In this review the factors involved in sensitization, detection of sensitization
      in the pretransplant period, various strategies tried in its prevention, and the
      current therapeutic approach to management of HSPs are discussed. Although
      prevention of sensitization is ideal, in practice a certain percentage of
      transplant recipients continue to exhibit hypersensitization despite all
      measures. Methods to remove preformed antibodies are effective but are expensive
      and not freely available. Aggressive immunosuppression based on cyclosporine
      (CsA) induction protocols constitute the mainstay in the management of HSPs. The
      availability of newer, potent, and more specific immunosuppressive agents,
      particularly those suppressing antibody synthesis, has opened a new avenue for
      more specific immunosuppression and better graft and patient survival following
      transplantation. Their clinical utility in improving patient and graft survival
      in HSPs needs to be evaluated.

PMID- 8873434
TI  - Immunologic tolerance in renal transplantation.
AB  - The current excellent short-term results of renal transplantation are achieved at
      the expense of complications of chronic immunosuppression. These include
      increased risk for infection, malignancy, and long-term deterioration of function
      ("chronic allograft nephropathy"). The induction of transplantation tolerance,
      the long-term acceptance of an allograft without continuous immunosuppression,
      has been a goal of transplant immunologists for the last 40 years. Unfortunately,
      this has been easier to achieve in rodents than in humans. Nevertheless, this
      body of research has significantly increased our knowledge of the workings of the
      immune system and specifically, how the body differentiates between "self" and
      "nonself". Using these insights, several promising approaches to the clinical
      induction of transplant tolerance have emerged and are undergoing clinical
      evaluation.

PMID- 8873436
TI  - Causes of long-term graft failure in renal transplantation.
AB  - A single-center experience of 980 consecutive renal transplant recipients treated
      with cyclosporine (CyA) was reviewed to analyze the causes of renal allograft
      loss and the factors affecting long-term renal survival in CyA-treated kidney
      transplants. In all, 217 grafts were lost during the observation period, with the
      most common causes of graft loss being chronic rejection (96 cases, 44%), death
      with a functioning graft (52 cases, 24%), glomerulonephritis (28 cases, 13%), and
      acute rejection (20 cases, 8%). The actuarial 10-year survival of patients with
      living and cadaveric grafts was 93% and 91%, respectively. The actuarial 10-year
      survival of living and cadaveric grafts was 70% and 63%, respectively. Patients
      were divided into two groups, namely a graft-survival group (n = 763) and a graft
      loss group (n = 217). There was no significant difference between the two groups
      in terms of sex, donor source, donor age, recipient age, duration of
      hemodialysis, retransplants, transfusions, presensitization, of HLA match. There
      was no difference between the graft-survival group and the graft-loss group in
      the mean CyA dose given or the mean CyA trough level measured at any time
      following transplantation. Acute rejection episodes occurred in patients from the
      graft-survival group (55%) as compared with those from the graft-loss group (83%;
      P < 0.00001). These data suggest that long-term graft survival in CyA-treated
      kidney transplant patients is primarily influenced by the occurrence of rejection
      episodes rather than by the drug dose or the duration of CyA administration. CyA
      nephrotoxicity was not the major risk factor for long-term graft survival in CyA
      treated renal transplants.

PMID- 8873437
TI  - A simplified technique for ureteroneocystostomy in renal transplantation.
AB  - From October 1988 to December 1993, 148 kidney transplants were carried out at
      our institution. An extravesical ureteral reimplantation technique resulting in a
      submucosal tunnel in the bladder wall was performed on 101 of the patients. For
      this technique, two small incisions are made at the outer part of the bladder
      wall until the mucosa is seen, then a submucosal tunnel is dissected between them
      and the graft's ureter is introduced and advanced in it (Alferez-Barry).
      Afterward the bladder mucosa is opened at the distal incision and the ureter is
      introduced into the bladder and fixed by a single direct anchorage stich
      (Taguchi). The minimal patients' follow-up is 18 months. Complications deriving
      from ureter reimplantation with this technique were present in 12.8% of the
      patients and included 4 cases of stenosis (3.9%), 4 cases of urinary fistula
      (3.9%), and 5 cases of hematuria (4.9%). We conclude that submucosal tunnelled
      ureteroneocystostomy with direct anchorage is a technique that simplifies kidney
      transplant surgery with good results. Ureteral direct anchorage can be used in
      any kind of ureteral anastomosis.

PMID- 8873438
TI  - The use of tacrolimus in renal transplantation.
AB  - Tacrolimus (FK 506) is a novel immunosuppressive agent that has been in clinical
      use for solid organ transplantation since 1989. Early clinical trials of
      tacrolimus in liver, heart, kidney, lung, and intestinal transplantation at the
      University of Pittsburgh have demonstrated it to be a safe and effective agent
      with several potential advantages over existing immunosuppressive drugs. More
      recently, phase I and II multicenter trials of tacrolimus for renal
      transplantation have been performed; however, data are not yet available from
      these trials. Our experience with this drug has demonstrated excellent 1- and 2
      year actuarial graft survival rates of 89% and 83%, respectively, in adult renal
      transplantation and 1- and 3-year graft survival rates of 98% and 85%,
      respectively in pediatric renal transplantation. A major advantage of tacrolimus
      noted in these trials was the ability to discontinue steroid therapy in
      approximately 50% of the patients. Tacrolimus has also shown efficacy as a rescue
      agent for renal allograft rejection failing conventional therapy in 74% of cases.
      This paper expands on these observations and focuses on the experience we have
      gained with the use of tacrolimus at our institution over the last 6 years.

PMID- 8873439
TI  - Cadaver kidney transplantation in patients more than 65 years old.
AB  - Elderly patients with end-stage renal disease often remain on dialytic therapy
      because they are at increased risk for mortality and morbidity. We placed 24
      cadaver kidney transplants into 24 patients aged 65-74 years between September 1,
      1985, and August 31, 1995. Rates of patient and graft survival were compared with
      those of 404 concurrent first cadaver-kidney transplant recipients between the
      ages of 20 and 44 years. The 5-year rates of patient and graft survival were not
      significantly different (86% versus 92% and 77% versus 63%, respectively; study
      group presented first). Primary cadaver kidney transplantation can be
      successfully performed in patients older than 65 years when a selection algorithm
      is applied to exclude active infection, active malignancy, unsuitable anatomy for
      technical success, high probability of operative mortality, and noncompliance.
      Pelvic arteriosclerosis and lower urinary tract abnormalities can cause
      intraoperative technical problems.

PMID- 8873440
TI  - The role of mycophenolate mofetil in clinical renal transplantation.
AB  - Mycophenolate mofetil (MM) is the ester derivative of mycophenolic acid (MPA),
      which exerts immunosuppressive activity by inhibiting de novo purine
      biosynthesis. Following animal models and pilot studies in human renal allograft
      recipients that confirmed MM's ability to prevent and half rejection episodes, 3
      large multicenter studies of 500 patients each were conducted in North America,
      Europe, and Australia to compare MM with azathioprine or placebo, all drugs being
      used in conjunction with prednisone and cyclosporine. The results demonstrated a
      statistically significant reduction in episodes of allograft rejection in the MM
      groups with a concomitant reduction in the use of antirejection therapy,
      especially antilymphocyte antibody therapy. Adverse-event profiles were similar
      for all groups, although there were slightly more gastrointestinal and tissue
      invasive cytomegalovirus (CMV) episodes in the MM groups. It is concluded that
      MM, which recently received Food and Drug Administration (FDA) approval in the
      United States, should be an important addition to the transplant physician's
      immunosuppressive armamentarium.

PMID- 8873442
TI  - Long-term follow-up of kidneys transplanted from elderly cadaveric donors.
AB  - This report examines the long-term results obtained in 50 patients transplanted
      between 1977 and 1990 with kidneys from cadaveric donors aged 55-70 (median 59)
      years. The recipients comprised 27 men and 23 women aged 8-68 (median 42) years.
      In all, 20 patients (40%) had end-stage renal disease on the basis of
      glomerulonephritis, whereas 8 (16%) were diabetic. Immunosuppression was induced
      with antilymphocyte globulin and maintained with azathioprine and prednisone in
      all patients in addition to cyclosporine in the 35 patients transplanted since
      1985. Immediate graft function occurred in 18 patients (36%), and 36 patients
      (72%) were off dialysis at 1 year posttransplant. Altogether, 25 patients (50%)
      had functioning grafts at 5 years posttransplant, and at up to 13 years of follow
      up (mean 5.8 years), 22 patients (44%) are off dialysis and their serum
      creatinine levels range from 0.8 to 3.8 mg/dl (mean 2.0 mg/dl). In all, 12
      patients (24%) expired from 2 months to 15.5 years posttransplant (mean 4.3
      years), and 5 of these patients died with functioning grafts. These 5 deceased
      recipients and the 22 who remain alive with functioning grafts had a mean antigen
      match of 2.27 with their donors. The other 23 patients whose grafts failed had a
      mean antigen match of 2.13 (P = 0.77). The 15 recipients who were transplanted
      prior to the cyclosporine era had lower 1- and 5-year allograft survival rates of
      67% and 47%, respectively, as compared with their counterparts, who took
      cyclosporine-based immunosuppression (74% and 51%, P = 0.58 and 0.76,
      respectively). Likewise, the 32 recipients with delayed graft function had lower
      1- and 5-year allograft survival rates of 66% and 47%, respectively, as compared
      with the group with immediate graft function (83% and 56%, P = 0.18 and 0.56,
      respectively). We conclude that acceptable long-term patient and graft survival
      may be achieved by transplanting these organs and that the degree of HLA matching
      does not affect their outcome significantly. Patients with immediate allograft
      function also tended to do better over the long term. Although cyclosporine-based
      immunosuppression was advantageous within 1 year of transplant, its beneficial
      effect was less marked 5 years out.

PMID- 8873441
TI  - Hyperfiltration nephropathy as a cause of late graft loss in renal
      transplantation.
AB  - Despite improved immunosuppression and early allograft survival, long-term
      survival of allografts remains unchanged. Late renal allograft loss has
      traditionally been considered to result from repeated or unresolved episodes of
      acute rejection that lead to chronic immune-mediated allograft rejection.
      However, late renal allograft loss is known to occur in the absence of prior
      episodes of acute rejection. It is therefore proposed that factors other than
      histocompatibility influence long-term allograft survival. Evidence for
      nonimmunologic factors contributing to late allograft loss is presented. The
      central hypothesis is that following renal allograft mass reduction (from any
      etiology), glomerular hyperperfusion and hyperfiltration develop and lead to
      progressive renal dysfunction, proteinuria, histopathologic allograft changes,
      and late allograft failure. Multiple nonimmunologic factors that could contribute
      to reduced renal mass and ultimately promote chronic allograft loss as a result
      of hyperfiltration nephropathy are presented along with possible therapeutic
      strategies for the prevention and treatment of glomerular hyperfiltration.

PMID- 8873443
TI  - Kidney transplantation in Saudi Arabia: a unique experience.
AB  - Kidney transplantation in the kingdom of Saudi Arabia began 16 years ago. In this
      relatively short period, transplantation has developed so quickly that Saudi
      Arabia currently has the largest cadaveric kidney transplantation program in the
      Moslem world. This article illustrates the achievements and progress made through
      the past and casts a light on differences in the transplantation practice in this
      part of the world.

PMID- 8873444
TI  - Review: subcellular traffic of the plasma membrane H(+)-ATPase in Saccharomyces
      cerevisiae.

PMID- 8873445
TI  - Flavin adenine dinucleotide binding is the crucial step in alcohol oxidase
      assembly in the yeast Hansenula polymorpha.
AB  - We have studied the role of flavin adenine dinucleotide (FAD) in the in vivo
      assembly of peroxisomal alcohol oxidase (AO) in the yeast Hansenula polymorpha.
      In previous studies, using a riboflavin (Rf) autotrophic mutant, an unequivocal
      judgement could not be made, since Rf-limitation led to a partial block of AO
      import in this mutant. This resulted in the accumulation of AO precursors in the
      cytosol where they remained separated from the putative peroxisomal AO assembly
      factors. In order to circumvent the peroxisomal membrane barrier, we have now
      studied AO assembly in a peroxisome-deficient/Rf-autotrophic double mutant (delta
      per1.rif1) of H. polymorpha. By sucrose density centrifugation and native gel
      electrophoresis, three conformations of AO were detected in crude extracts of
      delta per1.rif1 cells grown under Rf-limitation, namely active octameric AO and
      two inactive, monomeric forms. One of the latter forms lacked FAD; this form was
      barely detectable in extracts wild-type and delta per1 cells, but had accumulated
      in the cytosol of rif1 cells. The second form of monomeric AO contained FAD; this
      form was also present in delta per1 cells but absent/very low in wild-type and
      rif1 cells. In vivo only these FAD-containing monomers associate into the active,
      octameric protein. We conclude that in H. polymorpha FAD binding to the AO
      monomer is mediated by a yet unknown peroxisomal factor and represents the
      crucial and essential step to enable AO oligomerization; the actual
      octamerization and the eventual crystallization in peroxisomes most probably
      occurs spontaneously.

PMID- 8873446
TI  - Cloning, mapping and characterization of a genomic copy of the Lipomyces
      kononenkoae alpha-amylase-encoding gene (LKA1).
AB  - The expression in Saccharomyces cerevisiae and Schizosaccharomyces pombe of a
      cDNA copy of the Lipomyces kononenkoae IGC4052B alpha-amylase gene (LKA1), linked
      to the phosphoglycerate kinase gene (PGK1) promoter, resulted in the
      extracellular production of biologically active alpha-amylase (LKA1). However,
      transformation of S. cerevisiae and Schiz. pombe with a cosmid clone containing
      the complete genomic copy of LKA1, expressed from its native promoter, did not
      result in secretion of active alpha-amylase by any of the transformants. When the
      cDNA copy of LKA1 was expressed in S. cerevisiae under control of the wild-type
      L, kononenkoae promoter, biologically active alpha-amylase was secreted into the
      culture medium, indicating the recognition of the LKA1 promoter in S. cerevisiae.
      Sequence analysis of the GC-rich LKA1 promoter revealed canonical sequences that
      are homologous to the TATAAA, CAAT and CCAAT boxes and GCN4-binding sites that
      are present in several promoter sequences of S. cerevisiae. Primer extension
      analysis of LKA1 transcripts in L. kononenkoae indicated major initiation sites
      at nucleotides -64 and -65. S. cerevisiae and Schiz. pombe cells transformed with
      a plasmid containing the open reading frame of the genomic copy of LKA1, linked
      to the PGK1 promoter, did not produce alpha-amylase. Polymerase chain reaction
      mapping and sequence analysis revealed the presence of a 61-bp intron in the
      genomic copy of LKA1 that impaired synthesis of biologically active alpha-amylase
      in S. cerevisiae and Schiz. pombe. This intron contains donor, acceptor and
      branch sequences that correlate with the consensus sequences identified in the
      introns of split genes from Schiz. pombe and mammals. Pulsed-field gradient gel
      electrophoresis resolved at least eight chromosomal DNAs for L. kononenkoae
      IGC4052B and chromoblot analysis indicated that LKA1 is located on the second
      smallest chromosome, designated chromosome II.

PMID- 8873447
TI  - A useful colony colour phenotype associated with the yeast selectable/counter
      selectable marker MET15.
AB  - Strains of Saccharomyces cerevisiae bearing null alleles of the met15 gene are
      methionine auxotrophs and become darkly pigmented in the presence of Pb2+ ions
      (Ono et al. (1991). Appl. Env. Microbiol. 57, 3183-3186). We describe the cloning
      of a useful fragment of the MET15 locus which complements both the methionine
      requirement and the colony colour phenotype. This colony colour phenotype is very
      useful for genetic screens and may be applicable for use in other yeast species.
      The combination of the size of MET15, along with its counter-selectability and
      the colour of met15 mutations make this perhaps the most versatile yeast genetic
      marker.

PMID- 8873448
TI  - Identification of two CyP-40-like cyclophilins in Saccharomyces cerevisiae, one
      of which is required for normal growth.
AB  - We report the analysis of two Saccharomyces cerevisiae cyclophilins, Cpr6 and
      Cpr7, identified by their ability to interact in vivo with the transcriptional
      regulator Rpd3. Both cyclophilins have an extended carboxy-terminal region
      containing a three-unit tetratricopeptide repeat (TPR) motif and share
      significant amino acid identity with the mammalian cyclophilin CyP-40. Neither
      CPR6 nor CPR7 is essential but deletion of CPR7 results in a significant
      impairment of the rate of cell division. This is the first demonstration that a
      member of the cyclophilin family is required for normal cell growth.

PMID- 8873449
TI  - The targeting of Bacillus subtilis levansucrase in yeast is correlated to both
      the hydrophobicity of the signal peptide and the net charge of the N-terminus
      mature part.
AB  - We compared the ability of signal sequences from various Bacillus or yeast
      secreted proteins to direct Bacillus subtilis levansucrase into the secretion
      pathway of the yeast Saccharomyces cerevisiae. The efficiency of these sequences
      correlated with the overall hydrophobicity of their h-domain and was independent
      of their origin. Furthermore, the net charge of the proximal protein sequence
      downstream from the signal sequence contributed to the competence of the
      heterologous proteins to be secreted by yeast. Modification of this net charge
      allowed the protein to be translocated under the control of the yeast invertase
      signal sequence. Moreover, glycosylation of levansucrase did not modify
      significantly the fructosyl polymerase activity.

PMID- 8873450
TI  - Characterization of the SAC3 gene of Saccharomyces cerevisiae.
AB  - A temperature-sensitive mutation (act1-1) in the essential actin gene of
      Saccharomyces cerevisiae can be suppressed by mutations in the SAC3 gene. A DNA
      fragment containing the SAC3 gene was sequenced. SAC3 codes for a 150 kDa
      hydrophillic protein which does not show any significant similarities with other
      proteins in the databases. Sac3 therefore is a novel yeast protein. A nuclear
      localization of Sac3 is suggested by the presence of a putative nuclear
      localization signal in the Sac3 sequence. A SAC3 disruption mutation was
      constructed. SAC3 disruption mutants were viable but grew more slowly and were
      larger than wild-type cells. In contrast to the sac3-1 mutation, the SAC3
      disruption was not able to suppress the temperature sensitivity and the
      osmosensitivity of the act1-1 mutant. This demonstrates that act1-1 suppression
      by sac3-1 is not the result of a simple loss of SAC3 function. Furthermore, we
      examined the act1-1 and the sac3 mutants for defects in polarized cell growth by
      FITC-Concanavalin A (Con A)-labelling. The sac3 mutants showed a normal ConA
      labelling pattern. In the act1-1 mutant, however, upon shift to non-permissive
      temperature, newly synthesized cell wall material, instead of being directed
      towards the bud, was deposited at discrete spots in the mother cell.

PMID- 8873451
TI  - The translation initiation factor eIF4A from Schizosaccharomyces pombe is closely
      related to its mammalian counterpart.
AB  - We have isolated a cDNA clone encoding eIF4A from Schizosaccharomyces pombe. The
      deduced protein sequence is similar in length and sequence to other eIF4A
      proteins and exhibits highest similarity with the mammalian eIF4A protein.
      Hybridization with genomic DNA reveals two eIF4A genes located on two different
      chromosomes.

PMID- 8873452
TI  - Characterization of cwl1+, a gene from Schizosaccharomyces pombe whose
      overexpression causes cell lysis.
AB  - From a Schizosaccharomyces pombe genomic library we have isolated the gene cwl1+
      that causes cell lysis when it is overexpressed in the absence of an osmotic
      stabilizer. Southern hybridization showed that cwl1+ exists as a single copy in
      the S. pombe genome. The cwl1+ gene nucleotide sequence revealed a putative open
      reading frame of 924 bp encoding a polypeptide of 308 amino acids with a
      calculated Mt of 27000. The cwl1+ DNA hybridizes to a major RNA transcript of 1.5
      kb whose 5' end maps at a position 452 bp upstream from the predicted translation
      start. Comparison of the amino acid sequence with those included in the current
      databases, showed no significant similarity to any known sequences. Cells
      overexpressing the cwl1+ gene under the control of the S. pombe nmt inducible
      promoter displayed a reduced cell wall content, were unable to separate after
      division and lysed drastically in the absence of osmotic stabilizer. Disruption
      of the cwl1+ gene caused no noticeable phenotype.

PMID- 8873453
TI  - Current awareness on yeast.

PMID- 8873454
TI  - Effect of progressive systemic sclerosis on antral myoelectrical activity and
      gastric emptying.
AB  - In patients with progressive systemic sclerosis (PSS) suffering from chronic
      dyspepsia the stomach may be affected by this disease. The objective of this
      study was to investigate both antral myoelectrical activity and gastric emptying
      in PSS patients. Electrogastrography (EGG) was performed in 17 PSS patients (16
      female, one male, median age 58 years, range 32-74 years) with chronic dyspepsia.
      After an overnight fast during one hour in the fasting and one hour in the fed
      state after ingestion of a liquid-solid test meal (370 kcal; liquid phase labeled
      with 0.5 mCi 99mTc-colloid) antral electrical activity was measured by one pair
      of electrodes sonographically placed on the skin overlying the gastric antrum.
      Several EGG parameters including dominant frequency (DF), percentages of DF in
      the normal range (2-4 cycles per minute [cpm]), bradygastria (< 2 cpm) and
      tachygastria (4-10 cpm), dominant frequency instability coefficient (DFIC), and
      postprandial to preprandial power ratio (PR) were calculated. The data were
      correlated to results obtained in 20 age- and gender-matched healthy subjects. In
      addition, the data were compared to gastric retention of the radionuclide at 60
      min measured by simultaneous scintigraphy. The PSS patients did not reveal
      electrical disturbances. They even exhibited a significant postprandial decrease
      in DFIC, bradygastria, and tachygastria (ns) compared to healthy subjects. Over
      50% of the PSS patients showed a delayed gastric emptying. However, EGG did not
      correlate to radioscintigraphy significantly. Our results reflect an absent
      relationship between antral myoelectrical activity in EGG and gastric emptying.
      Therefore, electrogastrography is unsuitable to assess gastric involvement in
      PSS.

PMID- 8873456
TI  - EuroResidue III. Third conference on residues of veterinary drugs in food.

PMID- 8873455
TI  - Reduced serum levels of a soluble form of the human adhesion receptor CD58 (LFA
      3) in patients with inflammatory bowel disease.
AB  - The activation of monocytes, neutrophils, and B cells by T-lymphocytes appears to
      play a pivotal role in the pathophysiology of inflammatory bowel disease. The pan
      T cell marker CD2 and its ligand CD58 mediate these immune function. We asked
      whether serum levels of a soluble form of CD58 is altered in patients with
      inflammatory bowel disease. Soluble CD58 was measured in sera from 41 patients
      with Crohn's disease, 19 patients with ulcerative colitis, and 24 normal
      controls. Soluble CD58 levels were significantly decreased in sera from patients
      with ulcerative colitis and even more with Crohn's disease when compared to
      controls (p = 0.025 and p < 0.0001, respectively). Reduction of soluble CD58
      serum levels correlated significantly with various humoral (e.g. erythrocyte
      sedimentation rate: r = -0.48, p = 0.0002) and clinical parameters of disease
      activity (e.g. CDAI: r = -0.44, p = 0.005). In conclusion, serum levels of
      soluble CD58 are reduced in patients with inflammatory bowel disease. Since
      soluble CD58 can block the CD2/CD58 interaction further studies have to show
      whether the reduction of soluble CD58 in patients with inflammatory bowel disease
      contributes to T cell adhesiveness in the mucosa.

PMID- 8873457
TI  - Daily dietary chromium intake in Belgium, using duplicate portion sampling.
AB  - Daily dietary chromium intake in Belgium has been evaluated by sampling duplicate
      portions of food, heating them at an acidic pH in a microwave oven and then
      quantifying the chromium by atomic absorption spectrometry. The mean intake value
      (53 +/- 31 micrograms/day) is similar to levels found for most other countries
      and is situated at the lower end of the recommended range for a safe and adequate
      daily dietary intake.

PMID- 8873458
TI  - Trans fatty acids in margarines and shortenings marketed in Austria.
AB  - Margarines and shortenings available in Austria were repeatedly sampled in
      1991/1992 and the content of trans fatty acids (TFA) determined by using
      capillary GLC. Wide variations of the TFA contents with respect to intra- and
      inter-brand differences were observed. Diet margarines contained up to 1% TFA,
      while TFA concentrations in tub or stick margarines were much higher (15.7 +/-
      5.8% and 21.3 +/- 5.3%, respectively). A sub-set of samples was also purchased in
      1995 and a general reduction of the TFA content was noticed. Taking into account
      different market shares of certain margarine types, a weighted average of 15.7%
      TFA and 6.5% TFA was calculated for the 1991/1992 and the 1995 samples. Based on
      availability data the amount of TFA supplied with margarines was estimated to be
      3.7 g per person per day, while a more accurate method of measuring dietary
      intakes, i.e. diet history and food frequency data, approximates the amount of
      TFA supplied with margarines to be 1.5 g per person per day for the 1991/1992
      samples and 0.6 g for the 1995 samples.

PMID- 8873459
TI  - Variability of fatty acid content in pumpkin seeds (Cucurbita pepo L.).
AB  - Pumpkin (Cucurbita pepo L.) seed oil is a common salad oil which is produced in
      Slovenia, Hungary and the southern parts of Austria. It is dark green and has a
      high content of free fatty acids. The seed itself can be eaten. Due to its colour
      and the foam formation, the oil cannot be used for cooking. The content of
      vitamin E, especially gamma-tocopherol, is very high. The oil content of the
      pumpkin seed is about 50%. The variability in the oil content is very high
      resulting from a broad genetic diversity. Thus a breeding programme for
      increasing the oil productivity is very promising. The four dominant fatty acids
      are palmitic, stearic, oleic and linoleic acids. These four fatty acids make up
      98 +/- 0.13% of the total amount of fatty acids, others being found at levels
      well below 0.5%.

PMID- 8873460
TI  - Antioxidative effectiveness of some natural antioxidants in sunflower oil.
AB  - Sunflower oil has been oxidized at 25 and 100 degrees C in the presence and in
      the absence of 0.01, 0.02 and 0.05% 3,4-dihydroxybenzoic acid, caffeic acid,
      esculetin and fraxetin. 3,4-Dihydroxybenzoic acid shows no antioxidative activity
      at either temperature. Esculetin possesses a relatively low effectiveness at 100
      degrees C (stabilization factor F = 1.3 for 0.05% esculetin), and at 25 degrees C
      it does not improve the oxidative stability. Sunflower oil is more easy to
      stabilize at 100 degrees C: F = 3.0 for 0.05% fraxetin, and F = 1.9 for 0.05%
      caffeic acid. Native sunflower oil is much more difficult to stabilize than are
      its kinetically pure triacylglycerols.

PMID- 8873461
TI  - On the origin of benzene, toluene, ethylbenzene, and the xylenes in virgin olive
      oil--further results.
AB  - Investigations into the sources of contamination of virgin olive oil by gasoline
      components were concluded. Olives on the tree contained volatile aromatic
      hydrocarbons at concentrations exceeding those corresponding to the equilibrium
      with the environment. Present knowledge indicates that up to 10 micrograms/kg of
      benzene and 250 micrograms/kg for the sum of benzene, toluene, and the C2
      benzenes must be considered as possible background concentrations. Aside from the
      oil mills, the rooms for intermediate storage of the olives were found to be an
      important source of contamination by gasoline vapours, since they often contain
      vehicles and other gasoline-driven engines. Parking of a small, hot grass mower
      into a similar room released an amount of gasoline that was sufficient to
      contaminate the oil in olives above the proposed limit by a factor of 100.
      Recommendations are derived for the producers to avoid contamination of olive oil
      with gasoline components.

PMID- 8873462
TI  - Effect of natural fermentation on the content of inositol phosphates in lentils.
AB  - The effects of natural fermentation upon phytic acid and less phosphorylated
      inositol phosphates of Lens culinaris var vulgaris cultivar Magda-20 were
      investigated. Seven fermentation runs were made following a 2(2) complete
      factorial design with three replicated centre points to study the effect of
      different conditions of temperature (28, 35 and 42 degrees C) and broth
      concentration (79, 150 and 221 g/l). Samples were taken for each of them at daily
      intervals (0, 24, 48, 72 and 96 h). The pH value declined sharply in the first 24
      h of fermentation, becoming stabilized from this time. The relation between
      lactic acid and titratable acidity presented important differences between the
      different fermentations, ranging from 30-80%. Phytic acid (IP6), inositol
      pentakis (IP5), tetrakis (IP4) and tris-(IP3) phosphates were quantitatively
      determined. The content of total inositol phosphates showed a maximum reduction
      of 63% at 72 h under the fermentation conditions of 42 degrees C and 79 g/l.

PMID- 8873463
TI  - Chlorinated phenols in human milk.
AB  - The paper deals with the contamination of human milk with chlorinated phenols.
      The average and median concentrations of the chlorophenols investigated ranged
      from 0.75 to 9.74 micrograms.kg-1 and from being not detectable to 5.62
      micrograms.kg-1, respectively, for the different compounds. The highest average
      and median levels were found for pentachlorophenol and 2,4,5-trichlorophenol. The
      concentrations determined were below the permissible levels.

PMID- 8873466
TI  - Population structure of the yellow-footed rock-wallaby Petrogale xanthopus (Gray,
      1854) inferred from mtDNA sequences and microsatellite loci.
AB  - The yellow-footed rock-wallaby Petrogale xanthopus is considered to be
      potentially vulnerable to extinction. This wallaby inhabits naturally disjunct
      rocky outcrops which could restrict dispersal between populations, but the extent
      to which that occurs is unknown. Genetic differences between populations were
      assessed using mitochondrial DNA (control region) sequencing and analysis of
      variation at four microsatellite loci among three geographically close sites in
      south-west Queensland (P. x. celeris) and, for mtDNA only, samples from South
      Australia (P. x. xanthopus) as well. Populations from South Australia and
      Queensland had phylogenetically distinct mtDNA, supporting the present
      classification of these two groups as evolutionarily distinct entities. Within
      Queensland, populations separated by 70 km of unsuitable habitat differed
      significantly for mtDNA and at microsatellite loci. Populations separated by 10
      km of apparently suitable habitat had statistically homogeneous mtDNA, but a
      significant difference in allele frequency at one microsatellite locus. Tests for
      Hardy-Weinberg equilibrium and microgeographical variation at microsatellite loci
      did not detect any substructuring between two wallaby aggregations within a
      colony encircling a single rock outcrop. Although the present study was limited
      by small sample sizes at two of the three Queensland locations examined, the
      genetic results suggest that dispersal between colonies is limited, consistent
      with an ecological study of dispersal at one of the sites. Considering both the
      genetic and ecological data, we suggest that management of yellow-footed rock
      wallabies should treat each colony as an independent unit and that conservation
      of the Queensland and South Australian populations as separate entities is
      warranted.

PMID- 8873472
TI  - Isolation and characterization of microsatellite markers in the African catfish
      Clarias gariepinus (Burchell, 1822).

PMID- 8873473
TI  - The effect of proteases and iodination on the adherent behaviour of Plasmodium
      falciparum-infected erythrocytes.
AB  - Plasmodium falciparum-infected erythrocytes were treated with proteases (trypsin,
      chymotrypsin, pronase, or V8 protease) or iodinated and the effect of these
      treatments on the cytoadherent behaviour of the cells was determined. As
      previously observed, protease treatment reduced cytoadherence. However, it was
      also found that the P. falciparum-induced adhesin, pfalhesin, was not removed by
      protease treatment. Gelatin flotation experiments and scanning electron
      microscopical examination of the treated cells indicated that protease exposure
      resulted in changes in the knob structures on the cells, which are known to
      affect the adherent behaviour of the cells. Iodination was found to be an
      effective method of inactivating pfalhesin.

PMID- 8873474
TI  - Setaria digitata microfilaraemia in Mastomys coucha: an animal model for
      chemotherapeutic and immunobiological studies.
AB  - Intraperitoneal implantation of adult gravid females of the bovine filarial
      parasite, Setaria digitata in Mastomys coucha was found to induce microfilaraemia
      lasting for about 125 days. The microfilariae (mf) could be detected as early as
      4 days post-implantation (p.i.) and peak levels of about 30 mf in 20 microliters
      of blood were observed by 21 days. A significant positive correlation was found
      between mf density and the body weight of recipients pre-implantation. The
      implanted adult worms were generally viable only for less than 1 week.
      Implantation resulted in a significant decrease in total leucocytes and
      erythrocytes, induction of eosinophilia, splenomegaly and anti-erythrocyte
      autoantibodies. The microfilariae in circulation developed into 3rd-stage
      infective larvae (L3) when fed onto Aedes aegypti (refm, Liverpool strain). The
      mf in circulation were found to be eliminated by oral administration of
      diethylcarbamazine citrate, indicating the usefulness of this model for screening
      potential anti-microfilarial drugs. During the microfilaraemic phase, priming
      with tetanus toxoid (TT) resulted in significantly decreased production of anti
      toxin levels indicating a state of generalized immunosuppression. Induction of
      antibodies to various fractionated antigenic components of adult parasites could
      be demonstrated by enzyme immunoassay (EIA) in M. coucha implanted with live or
      cold-stunned adult worms. The S. digitata-M. coucha model thus is found amenable
      to perform chemotherapeutic and immunobiological investigations in experimental
      filariasis.

PMID- 8873475
TI  - Density-dependent processes in the transmission of human onchocerciasis:
      relationship between microfilarial intake and mortality of the simuliid vector.
AB  - In order to construct an analytical model of onchocerciasis transmission, it is
      necessary to elucidate the functional relationships of the various population
      rate processes taking place within the human and vector hosts. Two previous
      papers have explored the evidence for density-dependent regulation in relation to
      microfilarial intake by, and larval development within, the Simulium host. This
      paper investigates the survivorship of wild-caught blackfly samples fed on
      subjects with different intensities of Onchocerca volvulus microfilarial
      infection. Analyses were based on data for Guatemalan S. ochraceum s.l.
      (possessing a well-developed cibarial armature), West African S. damnosum s.l.
      (forest species), and South Venezuelan S. guianense (the latter two lacking a
      toothed cibarium). The mean survival times of samples of the 3 species, kept
      under laboratory conditions, decreased as parasite intake increased, the rate of
      mortality being dependent on the fly's age (measured as time post-feeding) and on
      the worm load acquired. An empirical, time-dependent hazard function was fitted
      to observed death rates/fly/day which rose very shortly after engorgement,
      declined subsequently, and rose again throughout the extrinsic incubation period
      of the parasite. The parameters of this hazard model were all positively
      correlated with the density of microfilariae in the bloodmeal. Expressions of
      survivorship and life-expectancy as explicit functions of time post-feeding and
      mean parasite intake were derived. The average expectation of life at engorgement
      for uninfected flies in the laboratory was estimated to be around 1 week for
      both, armed and unarmed blackflies. Residual life-expectancy decreased with time
      post-feeding and microfilarial load in both categories of vectors. This decline
      (resulting from age- and parasite-dependent mortality rates) was much more
      pronounced in those species lacking a toothed fore-gut. Whilst a fraction of
      heavily infected S. ochraceum was able to survive the latent period of the
      parasite, being therefore potentially capable of transmitting the infection,
      equivalent worm loads in S. guianense resulted in a drastic reduction of the
      expectation of infective life. These results provide additional evidence to
      support the hypothesis that, in the case of intrinsically susceptible vectors,
      unarmed simuliids are more efficient at low microfilarial loads, when the
      transmission rate from human to vector host is higher, and parasite-induced fly
      mortality is negligible. The opposite takes place in armed flies, which perform
      poorly at low parasite burdens and better at heavier loads, with little parasite
      induced vector death.

PMID- 8873477
TI  - Ultrastructural localization of Sm28 GST protective antigen in Schistosoma
      mansoni adult worms.
AB  - The localization of the 28 kDa Schistosoma mansoni glutathione S-transferase
      (Sm28 GST) has been investigated using immunohistochemistry and electron
      microscopy and the results compared with previously published data. This study
      confirms the wide distribution of this antigen in the parasite. In male and
      female worms, Sm28 GST is localized in the tegument, the parenchyma, the
      oesophageal epithelium and in genital organs. Sm28 GST was clearly detected in
      germinal and sustentacular cells. The decrease of staining intensity during the
      differentiation of germinal cells suggests a down-regulated expression of the
      molecule. At the ultrastructural level, this antigen was abundant in nuclei and
      less present in the cytoplasm. The marked heterogeneity observed in the staining
      of individual worms indicates that Sm28 GST seems to be closely associated with
      the parasite's metabolism. The results are discussed in relation to the
      biological and protective functions of the protein.

PMID- 8873476
TI  - Experimental Schistosoma bovis infection in goats. Circulating antigen and
      antibody responses to egg and adult worm antigens during infection and following
      treatment with praziquantel.
AB  - Circulating antigen levels and antibody responses in Schistosoma bovis-infected
      West African Dwarf goats were evaluated during infection and following treatment
      with praziquantel (60 mg/kg) 13 weeks post-infection. One day, 1 week and 4 weeks
      post-treatment, subgroups of goats were sacrificed and perfused for worm
      recovery. For comparison, parasite-free control animals were included. Blood and
      faecal samples were collected biweekly. Two gut-associated schistosome antigens,
      circulating cathodic and circulating anodic antigen (CCA and CAA) and 3 specific
      antibody responses (total Ig, IgG and IgM) were measured. For specific antibody
      detection, crude S. bovis adult worm and egg homogenates were used. The level of
      CCA in the infected groups was significantly elevated from the time of onset of
      egg excretion onwards. However, following treatment, the CCA titres dropped to
      control levels within 1 week post-treatment. Strong positive correlations were
      found between CCA levels and worm counts and faecal egg counts during peak egg
      excretion. The correlations of CAA and specific antibody titres to egg and worm
      counts were poor. The antibody responses were all significantly elevated in the
      infected goats during patency, but only marginally affected by the treatment.
      Hence, CCA proved to be superior by correlating strongly to the level of
      infection and by being a sensitive indicator of the effect of treatment.

PMID- 8873478
TI  - Neutrophil granule proteins: evidence for the participation in the host reaction
      to skin microfilariae of Onchocerca volvulus after diethylcarbamazine
      administration.
AB  - The participation of neutrophil granulocytes in the cellular reaction to skin
      microfilariae of Onchocerca volvulus was studied by immunohistochemistry. Skin
      biopsies were obtained from adult Liberian and Ugandan patients with generalized
      onchocerciasis after exposure to topically applied diethylcarbamazine (DEC) and
      from untreated patients. After DEC many damaged microfilariae were observed
      either in dermal infiltrates or in epidermal microabscesses consisting both of
      neutrophils and eosinophils. Infiltrates and microabscesses contained some intact
      granulocytes and many neutrophils releasing myeloperoxidase, elastase,
      lactoferrin, defensin, lysozyme, alpha 1-antitrypsin and alpha 1
      antichymotrypsin. Eosinophils discharged peroxidase and cationic proteins.
      Released granule proteins and remnants of disrupted granulocytes were found on
      the surface and in close proximity of damaged microfilariae in dermal infiltrates
      and epidermal microabscesses. In larger microabscesses neutrophils were
      predominant. These observations show that neutrophils and not only eosinophils
      recruit, accumulate, localize around and release their helminthotoxic granule
      proteins such as myeloperoxidase onto or closely around skin microfilariae of O.
      volvulus after topical DEC administration. The association between these
      processes and the damage of the microfilariae indicated that neutrophils together
      with eosinophils attack and damage microfilariae of O. volvulus after DEC
      treatment in the skin.

PMID- 8873479
TI  - Characterization of intestinally active proteinases of cyst-nematodes.
AB  - Cryostat sections of juvenile and adult female stages of the soybean cyst
      nematode, Heterodera glycines, were incubated with 4 different naphthylamide
      linked peptide substrates to localize and characterize proteinase activity within
      the animal. Detected activity was restricted to the intestine and 2 distinct
      classes of proteinase were identified on the basis of substrate specificity and
      sensitivity to plant proteinase inhibitors. A cathepsin L-like cysteine
      proteinase activity capable of hydrolysing the synthetic substrates Z-Ala-Arg-Arg
      MNA and Z-Phe-Arg-MNA but not Z-Arg-Arg-MNA or L-Arg-NA was inhibited by an
      engineered variant of a cysteine proteinase inhibitor from rice (Oc-I delta D86).
      The cleavage of Z-Phe-Arg-MNA was sensitive to inhibition by a combination of Oc
      I delta D86 and cowpea trypsin inhibitor (CpTI). Degenerate oligonucleotide
      primers were used to amplify fragments of cysteine proteinase genes from 2 cyst
      nematodes, H. glycines and Globodera pallida. Comparison of the H. glycines
      fragment with known genes established highest homology to cathepsin L-like genes.
      In contrast, the amplified G. pallida fragment displayed greatest homology to
      cathepsin B-like genes from Caenorhabditis elegans.

PMID- 8873483
TI  - Take off the stethoscope and put on a microphone.

PMID- 8873484
TI  - Diabetic muscle infarction.
AB  - PURPOSE: To describe the clinical, histologic, and radiologic findings in
      patients with diabetic muscular infarction (DMI). MATERIALS AND METHODS:
      Descriptive case series of 3 patients with DMI and 22 previously reported cases
      (MEDLINE data base search) in the English literature are presented. RESULTS:
      Diabetic muscular infarction is usually seen in patients with long-standing
      insulin-dependent diabetes and multiple end-organ microvascular complications.
      Two-thirds of patients with DMI are women, with a mean age at presentation of 39
      +/- 12 years. The typical clinical presentation includes abrupt onset of thigh
      pain and tenderness. There is a palpable, painful mass, with swelling and
      induration of the surrounding tissue without systemic symptoms or signs. The
      painful lesion persists for weeks, occasionally with exacerbations of symptoms,
      then spontaneously resolves over several weeks to months. Recurrent episodes are
      reported in half of the patients. Muscles commonly affected are the vastus
      lateralis, thigh adductors, and biceps femoris; but calf muscles may be involved
      as well. Active pathologic changes in the muscle are more sensitively evaluated
      with T2-weighted sequences on magnetic resonance (MR) imaging, which shows high
      intensity in involved muscle. Histologic features of DMI consist of large areas
      of muscle necrosis and edema. Regenerating muscle fibers and lymphocytic
      interstitial infiltration may be present. CONCLUSION: Diabetic muscular
      infarction is a rare complication of diabetes mellitus. In most patients, the
      diagnosis can be made when the characteristic clinical presentation is combined
      with a typical MR imaging results. Muscle biopsy can be helpful in establishing
      the diagnosis of DMI, but histologic findings are not specific. Awareness of this
      syndrome plus MR imaging as the first diagnostic test should lead to the correct
      diagnosis and shorter hospitalization.

PMID- 8873485
TI  - Sleep-disordered breathing in women: occurrence and association with coronary
      artery disease.
AB  - PURPOSE: To examine the occurrence of sleep apnea and nocturnal hypoxemia in
      women with and without coronary artery disease (CAD) and to investigate the
      relationship between sleep-disordered breathing and coronary artery disease.
      PATIENTS AND METHODS: In a case-control study, 102 cases were randomly selected
      among women with angina pectoris and angiographically verified coronary disease.
      Fifty age-matched controls without known heart disease were selected from the
      population registry. Pulse oximetry, oronasal thermistors, body position
      indicator, and recording of body and respiratory movements were used to quantify
      oxygen desaturations (the number of desaturations > or = 4% per hour of sleep,
      oxygen desaturation index [ODI]) and apneas (the number of apneas or hypopneas
      per hour of sleep, apnea-hypopnea index [AHI]). RESULTS: Women with CAD had a
      high occurrence of disordered breathing measured as AHI > or = 5, 54% (n = 54),
      AHI > or = 10, 30% (n = 30) or ODI > or = 5, 34% (n = 35) while the same
      proportions in controls were 20% (n = 10, P < 0.0001), 10% (n = 5, P < 0.01) and
      18% (n = 9, P < 0.05), respectively. In a multiple logistic regression model,
      sleep apnea (AHI > or = 5), hypertension, and smoking habits were independent
      predictors of CAD with odds ratios of 4.1 (95% confidence interval [CI] 1.7 to
      9.7, P < 0.01), 3.4 (CI 1.3 to 8.9, P < 0.05) and 2.4 (CI 1.0 to 5.7, P < 0.05),
      respectively. CONCLUSION: Sleep apnea is common in women with CAD and remains as
      a significant predictor of coronary disease after adjustment for age, body mass
      index, hypertension, smoking habits, and diabetes.

PMID- 8873486
TI  - Human immunodeficiency virus type 1-related transient neurological deficits.
AB  - PURPOSE: To characterize human immunodeficiency virus type 1 (HIV-1)-related
      transient neurological deficit (TND). DESIGN: A 3-year prospective study based at
      a tertiary referral center. METHODS: Patients with TND in the absence of an
      opportunistic infection, neoplasm, neurosyphilis, or seizure were recruited and
      further investigated. The frequency of hospital admission for these patients was
      compared with those who were HIV-1 seronegative and with those who were admitted
      for HIV-1-related thromboembolic events. RESULTS: Twenty-seven patients were
      identified: mean age of 39 +/- 9 years; CD4+ cell count of 130 +/- 80/microL.
      Seven patients had no history of an AIDS-defining illness. Hemiparesis and
      hemisensory disturbance occurred in 23 patients (85%); 15 had preexisting ADC, 7
      stage 1 and 8 stage 2; 3 developed ADC after 18 months. Thirteen patients had
      multiple attacks and 5 had more than 20; 2 patients developed a cerebral infarct.
      No cause for the TND was identified in 8 patients (30%). Anticardiolipin
      antibodies were found in 70% and low protein S levels in 53% which was
      significantly more often than in a neurologically normal group with similarly
      advanced HIV-1 disease. The frequency of admission was 0.8% whereas the frequency
      for similar TND in HIV-1-seronegative patients was 0.4% and the frequency for HIV
      1-related thromboembolic events was 0.9%. CONCLUSIONS: Transient neurological
      deficits occur in advanced HIV-1 disease and are often associated with ADC,
      elevated concentrations of anticardiolipin antibodies, and low protein S levels.
      Future studies will need to define the precise role of these associations in the
      pathogenesis of HIV-1-related TND.

PMID- 8873487
TI  - Osteoporosis in lung transplantation candidates with end-stage pulmonary disease.
AB  - PURPOSE: Fractures, a common complication of cardiac and liver transplantation,
      have not been reported in association with lung transplantation. However, many
      patients with end-stage pulmonary disease have multiple risk factors for
      osteoporosis, and several studies have suggested that osteoporosis before
      transplantation may increase the risk of fracture after transplantation.
      Therefore, we evaluated a group of patients with end-stage pulmonary disease who
      were awaiting lung transplantation to determine the prevalence of osteoporosis.
      METHODS: Seventy patients (aged 18-70 years) were evaluated consecutively with
      bone densitometry by dual-energy x-ray absorptiometry. The patients were
      predominantly Caucasian (96%). Bone mass was expressed as bone mineral density
      (BMD; g/cm2), as the number of standard deviations (SD) below peak bone mass (T
      score), and as bone mineral apparent density (BMAD; g/cm3), a measurement that
      minimizes the effects of bone size on BMD. Spine radiographs were obtained in a
      subset of 50 consecutive patients to detect vertebral compression fractures.
      Vitamin D status was assessed with serum concentrations of 25-hydroxyvitamin D.
      The patients were sorted into groups by pulmonary diagnosis: chronic obstructive
      pulmonary disease (COPD; n = 28); cystic fibrosis (n = 11); idiopathic pulmonary
      fibrosis; and other lung diseases (Other; n = 31). RESULTS: In the group as a
      whole, osteoporosis (T score below -2.5) was present in 30% of the patients at
      the lumbar spine and 49% at the femoral neck. Osteopenia (T score between -1 and 
      2.5) was present in an additional 35% at the lumbar spine and 31% at the femoral
      neck. The average femoral neck T score of patients with COPD and cystic fibrosis
      fell into the osteoporotic range (-2.7 +/- 0.3 and -2.6 +/- 0.3, respectively),
      significantly (P < 0.01) below that of the patients in the Other category (-1.5
      +/- 0.3). The average lumbar spine T score fell into the osteopenic range in all
      three groups. Low BMAD in patients with cystic fibrosis confirmed that their low
      BMD was not due to their smaller body size. The prevalence rate of vertebral
      fractures was 29% in patients with COPD and 25% in those with cystic fibrosis.
      Vitamin D deficiency (25-hydroxyvitamin D levels < or = 10 ng/ml) was present in
      36% of patients with cystic fibrosis and 20% with COPD and Other lung diseases.
      Lumbar spine BMD tended to be lower in cystic fibrosis patients with vitamin D
      deficiency. Patients with exposure to glucocorticoids (n = 46) had significantly
      more vertebral fractures (P < 0.05) and duration of exposure correlated
      negatively with lumbar spine BMD (r = -0.398; P = 0.008). COPD and Other patients
      not on glucocorticoids had mild lumbar spine osteopenia (0.972 +/- 0.06 g/cm2; T
      = -1.2 +/- 0.6). Very few of the patients on glucocorticoids were on any regimen
      to prevent osteoporosis. CONCLUSIONS: Osteoporosis and vitamin D deficiency are
      extremely common in patients with end-stage pulmonary disease. Only 34% of
      patients had normal lumbar spine BMD and only 22% had normal BMD at the hip.
      Patients with cystic fibrosis and glucocorticoid-treated patients with COPD were
      most severely affected. Therapies to prevent bone loss and treat established
      osteoporosis are uncommonly utilized in glucocorticoid-treated patients with end
      stage pulmonary disease. Candidates for lung transplantation should be evaluated
      for osteoporosis and vitamin D deficiency at the time of acceptance to the
      transplant waiting list.

PMID- 8873488
TI  - Effect of a multidisciplinary intervention on medication compliance in elderly
      patients with congestive heart failure.
AB  - PURPOSE: The objectives of this investigation were to prospectively assess
      medication compliance rates in elderly patients with congestive heart failure, to
      identify factors associated with reduced compliance, and to evaluate the effect
      of a multidisciplinary treatment approach on medication adherence. PATIENTS AND
      METHODS: A total of 156 patients > or = 70 years of age (mean, 79.4 +/- 6.0; 67%
      female, 65% nonwhite) hospitalized with congestive heart failure were evaluated
      prospectively. Prior to discharge, patients were randomized to the study
      intervention (n = 80) or conventional care (n = 76). The intervention consisted
      of comprehensive patient education, dietary and social service consultations,
      medication review, and intensive postdischarge follow-up. Detailed data were
      collected on all prescribed medications at the time of discharge, and compliance
      was assessed by pill counts 30 +/- 2 days later. RESULTS: The overall compliance
      rate during the first 30 days after discharge was 84.6 +/- 15.1% (range, 23.1
      100%). Compliance was 87.9 +/- 12.0% in patients randomized to the study
      intervention, compared with 81.1 +/- 17.2% in the control group (P = 0.003). A
      compliance rate of > or = 80% was achieved by 85.0% of the treatment group versus
      69.7% of the control group (P = 0.036). By multivariate analysis, assignment to
      the treatment group was the strongest independent predictor of compliance (P =
      0.008). Other variables included in the model were Caucasian race (P = 0.044) and
      not living alone (P = 0.09). CONCLUSIONS: A multidisciplinary treatment strategy
      is associated with improved medication compliance during the first 30 days
      following hospital discharge in elderly patients with congestive heart failure.
      Improved compliance may contribute to improved outcomes in these patients.

PMID- 8873489
TI  - Fever duration in hospitalized acute pyelonephritis patients.
AB  - PURPOSE: To study persistence of fever in treated pyelonephritis with respect to
      guidelines recommending investigation and modification of therapy after 2 to 3
      days of fever. PATIENTS AND METHODS: A retrospective chart review was made of 70
      patients hospitalized for febrile pyelonephritis at a community hospital in
      Canada. RESULTS: Median duration of fever was 34 hours; persistence of fever at
      48 and 72 hours was 26% and 13%, respectively. No patients had complications such
      as intrarenal or perirenal abscess. Prolonged fever was independently associated
      with increasing baseline creatinine (P = 0.0001), younger age (P = 0.027), and
      increasing total leukocyte count (P = 0.026). Results of ultrasonography and
      intravenous urograms were not predictors of fever duration. CONCLUSION: Fever in
      treated pyelonephritis can take 4 days to resolve, and routine urologic
      investigation after 2 to 3 days of fever may be unwarranted.

PMID- 8873490
TI  - Health status in patients with chronic fatigue syndrome and in general population
      and disease comparison groups.
AB  - PURPOSE: To measure the functional status and well-being of patients with chronic
      fatigue syndrome (CFS), and compare them with those of a general population group
      and six disease comparison groups. PATIENTS AND METHODS: The subjects of the
      study were patients with CFS (n = 223) from a CFS clinic, a population-based
      control sample (n = 2,474), and disease comparison groups with hypertension (n =
      2,089), congestive heart failure (n = 216), type II diabetes mellitus (n = 163),
      acute myocardial infarction (n = 107), multiple sclerosis (n = 25), and
      depression (n = 502). We measured functional status and well-being using the
      Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which is a self
      administered questionnaire in which lower scores are indicative of greater
      impairment. RESULTS: Patients with CFS had far lower mean scores than the general
      population control subjects on all eight SF-36 scales. They also scored
      significantly lower than patients in all the disease comparison groups other than
      depression on virtually all the scales. When compared with patients with
      depression, they scored significantly lower on all the scales except for scales
      measuring mental health and role disability due to emotional problems, on which
      they scored significantly higher. The two SF-36 scales reflecting mental health
      were not correlated with any of the symptoms of CFS except for irritability and
      depression. CONCLUSION: Patients with CFS had marked impairment, in comparison
      with the general population and disease comparison groups. Moreover, the degree
      and pattern of impairment was different from that seen in patients with
      depression.

PMID- 8873491
TI  - Dynamic changes of plasma lipids and lipoproteins in patients after transient
      ischemic attack or minor stroke.
AB  - PURPOSE: Only few data are available concerning variations of lipids and
      lipoproteins in the acute stage after ischemic cerebrovascular events. It was the
      aim of this study to investigate whether the lipid and lipoprotein levels
      obtained in the first few days after a transient ischemic attack (TIA) or a minor
      stroke (MS) actually reflect "correct' values or "changed' (ie, false low)
      values, as in patients after acute myocardial infarction. PATIENTS AND METHODS:
      Total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and
      triglyceride (TG) levels of 37 unselected patients with TIA or MS were determined
      within 12-48 hours (Group A) or within 49-168 hours (Group B) after the acute
      event. After a mean observation period of 15.3 months, all patients were re
      examined; the results were compared with those of the baseline evaluation.
      RESULTS: At the time of the baseline evaluation, TC and LDL-C levels of Group B
      patients were significantly lower than Group A levels. At the end of the
      observation period, however, Group A and Group B patients did not differ with
      regard to all four parameters. In comparison with the baseline examination, the
      values of Group A patients had not changed. In Group B patients, however, TC, HDL
      C, LDL-C, and TG levels had significantly increased. CONCLUSION: Our results
      strongly suggest that lipid and lipoprotein levels of patients with TIA or MS
      should be assessed within a maximum of 48 hours after the acute event. If the
      examination cannot be performed within that period, the determination of reliable
      values is possible only after several weeks or months.

PMID- 8873492
TI  - Immunomodulation by blood transfusion: an evolving scientific and clinical
      challenge.

PMID- 8873493
TI  - Strategic planning for academic health centers.
AB  - The mission, indeed the very existence, of the traditional academic health center
      is under siege. Changes in the financing and delivery of health care threaten the
      clinical revenue used to subsidize the tripartite mission of education, research,
      and patient care. Market practices, driven by the growth of managed care, will
      intensify the impact of declining revenue to threaten the actual patient base
      necessary to sustain these endeavors. The survival of academic health centers
      depends on their ability to change. This change will not be easy, and the size of
      the collective academic medical establishment will decrease. Successful
      enterprises will be those that go beyond incremental, reactive adjustments.
      Nothing short of organizational redesign, creation of strategic partnerships, and
      adopting a cybernetic model of continuous measurement, improvement and
      adaptability will suffice. Using the elements of a strategic planning exercise,
      this paper reviews the background issues that have produced the current
      predicament and explores the strengths and weaknesses inherent in academic
      institutions. Elements of an "idealized" academic health center are postulated
      and, finally, specific strategies that might be considered in creating a relevant
      and secure future are proposed.

PMID- 8873494
TI  - Human immunodeficiency virus infection and acquired immunodeficiency syndrome
      among North American women.
AB  - Women constitute the fastest growing segment of adults with acquired
      immunodeficiency syndrome (AIDS), representing 18% of all cases in the United
      States in 1994. Heterosexual transmission is now the dominant route by which
      women are infected. Recent reports indicate that although certain manifestations
      may be different in women than in men, the rate of clinical progression is
      similar when they receive comparable medical treatment. Antiretroviral therapy is
      equally as effective in women as in men. As in men, Pneumocystis carinii
      pneumonia is the most frequent AIDS-defining diagnosis in women. Candida
      esophagitis and ulcers secondary to herpes simplex virus are more common in
      women. Kaposi's sarcoma is rare. The prevalence of humanpapilloma virus infection
      and cervical neoplasia is increased in HIV-seropositive women. Vaginitis due to
      candida, trichomonas, and bacterial vaginosis are common findings among human
      immunodeficiency virus seropositive women. The clinical course and response to
      therapy in certain sexually transmitted diseases (syphilis and herpes) may be
      altered. The use of zidovudine during pregnancy and delivery has been associated
      with a 67.5% reduction in vertical transmission.

PMID- 8873495
TI  - Protein-losing enteropathy and massive pulmonary embolism in a patient with giant
      inflammatory polyposis and quiescent ulcerative colitis.

PMID- 8873496
TI  - Cardiac, pancreatic, and liver abnormalities in a patient with coxsackie-B
      infection.

PMID- 8873497
TI  - Olecranon bursitis in patients with chronic obstructive pulmonary disease.

PMID- 8873498
TI  - Strip it! A method to teach residents cost-effective test ordering.

PMID- 8873499
TI  - Clinical implications of insulin resistance syndrome.

PMID- 8873500
TI  - Elevation of blood pressure after erythropoietin therapy.

PMID- 8873501
TI  - Medicine chairs' views on the impact of managed care on departments of internal
      medicine.

PMID- 8873502
TI  - A potent new bisphosphonate for Paget's disease of bone.

PMID- 8873504
TI  - Utility of routine admission chest radiographs in patients with acute
      gastrointestinal hemorrhage admitted to an intensive care unit.
AB  - PURPOSE: To determine the diagnostic yield of routine admission chest radiographs
      in patients with acute gastrointestinal (GI) hemorrhage and clinical predictors
      of radiographic abnormalities. PATIENTS AND METHODS: The study was a
      retrospective series of 202 adult patients with GI hemorrhage admitted to
      intensive care units at an academic medical center. Routine admission chest
      radiographs were obtained in 161 patients. These radiographs were reviewed by a
      study radiologist blinded to the study purpose. The radiologist scored
      radiographic abnormalities into categories of "minor" or "major," "new" or
      "previously known," and "with an intervention" or "without an intervention."
      Nominal logistic regression explored the data for clinical features that
      identified patients with major new radiographic abnormalities with or without an
      intervention. RESULTS: Minor radiographic abnormalities were noted in 23 (14.3%)
      patients, of whom 17 (10.6%) patients had "new" (previously unknown)
      abnormalities. No minor abnormality prompted a therapeutic or diagnostic
      intervention. Major radiographic abnormalities were detected in 21 (13.0%)
      patients, of whom 19 (11.8%) had new findings. Major new findings prompted
      interventions in only 9 (5.6%) of patients. A history of lung disease and an
      abnormal lung physical examination predicted major new radiographic findings (P =
      0.0001, sensitivity 79%, negative predictive value 96%). These variables also
      identified major new abnormalities that prompted interventions (P = 0.007,
      sensitivity 89%, negative predictive value 99%). Use of the logistic regression
      model to select patients for admission chest radiographs decreased charges from
      $1,068 to $580 for each detected major new radiographic abnormality and from
      $2,254 to $1,087 for major new radiographic abnormalities that prompted an
      intervention. CONCLUSION: These data indicate that routine chest radiographs have
      a low yield in detecting major new radiographic abnormalities in patients with
      acute GI hemorrhage. Clinical criteria, available at the time of admission, may
      be useful for selecting patients for chest radiographic evaluations.

PMID- 8873503
TI  - Biochemical and radiologic improvement in Paget's disease of bone treated with
      alendronate: a randomized, placebo-controlled trial.
AB  - PURPOSE: The potent bisphosphonates offer great promise in the management of
      Paget's disease of bone, but are currently available only as parenteral
      preparations in most countries. There is a need for a well-tolerated, oral
      therapy. Furthermore, none of the currently available therapies have been
      rigorously demonstrated to heal the lytic bone lesions characteristic of this
      condition. Alendronate is a potent new oral aminobisphosphonate that has shown
      promising effects on Paget's disease in preliminary studies. METHODS: We report a
      double-blind, randomized comparison of oral alendronate 40 mg/day and placebo
      over 6 months in 55 patients with Paget's disease. Efficacy was determined from
      measurements of biochemical indices of bone turnover (serum alkaline phosphatase
      and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions.
      RESULTS: N-telopeptide excretion declined by 86% and serum alkaline phosphatase
      by 73% in patients receiving alendronate, but remained stable in patients
      receiving placebo (P < 0.001 between groups for both indices). Responses were
      similar whether or not patients had previously received bisphosphonate treatment.
      Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty
      eight percent of alendronate-treated patients showed radiologic improvement in
      osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between
      groups comparison). No patient in either group showed worsening of osteolysis.
      Bone histomorphometry indicated that alendronate tended to normalize turnover
      indices. There was no evidence of abnormal mineralization in bone biopsies taken
      from 12 alendronate-treated subjects. The treatment was well tolerated.
      CONCLUSION: Oral alendronate appears to be a safe and effective therapy for
      Paget's disease and results in healing of lytic bone lesions.

PMID- 8873505
TI  - Intranasal nicotine spray does not augment the adverse effects of cigarette
      smoking on myocardial oxygen demand or coronary arterial dimensions.
AB  - PURPOSE: Nicotine replacement therapy has become a popular therapy for smokers
      attempting to stop smoking. Unfortunately, some subjects continue to smoke while
      receiving it. Since nicotine is believed to be the primary constituent of
      cigarette smoke responsible for its acute adverse effects on myocardial oxygen
      supply and demand, concomitant nicotine replacement therapy and smoking
      theoretically could provoke a marked decrease in myocardial oxygen supply and
      increase in demand. This study was performed to assess the effects of cigarette
      smoking with and without concomitant intranasal nicotine spray on: (a) myocardial
      oxygen demand, (b) coronary arterial dimensions, and (c) the development of acute
      cardiovascular tolerance. PATIENTS AND METHODS: In 19 smokers referred for
      cardiac catheterization for the evaluation of chest pain, we assessed the effects
      of cigarette smoking with and without concomitant intranasal nicotine spray on:
      (a) heart rate-systolic arterial pressure product (an estimate of myocardial
      oxygen demand), (b) coronary arterial dimensions (measured with computer-assisted
      quantitative arteriography), and (c) the development of acute cardiovascular
      tolerance. RESULTS: Smoking a first cigarette increased rate pressure product (P
      < 0.001) and decreased coronary arterial dimensions (P < 0.0001). Subsequently,
      neither variable was altered by intranasal nicotine spray or a second cigarette.
      Despite a substantial increase in serum nicotine concentration with nicotine
      spray and smoking, acute cardiovascular tolerance appears to develop.
      CONCLUSIONS: Cigarette smoking causes an increase in myocardial oxygen demand and
      concomitant coronary arterial vasoconstriction. However, further increases in the
      serum nicotine concentration do not cause a greater increase in demand or
      decrease in coronary arterial dimensions. These data suggest that humans acutely
      develop tolerance to an increasing nicotine concentration, thereby helping to
      explain the apparent lack of a potential synergistic adverse effect associated
      with continued smoking during nicotine replacement therapy.

PMID- 8873506
TI  - Functional status in patients with chronic fatigue syndrome, other fatiguing
      illnesses, and healthy individuals.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is a condition that may be associated
      with substantial disability. The Medical Outcomes Study Short-Form General Health
      Survey (SF-36) is an instrument that has been widely used in outpatient
      populations to determine functional status. Our objectives were to describe the
      usefulness of the SF-36 in CFS patients and to determine if subscale scores could
      distinguish patients with CFS from subjects with unexplained chronic fatigue
      (CF), major depression (MD), or acute infectious mononucleosis (AIM), and from
      healthy control subjects (HC). An additional goal was to ascertain if subscale
      scores correlated with the signs and symptoms of CFS or the presence of
      psychiatric disorders and fibromyalgia. DESIGN: Prospectively collected case
      series. SETTING: Patients with CFS and CF were seen in a university-based
      referral clinic and had undergone a complete medical and psychiatric evaluation.
      Other study subjects were recruited from the community to participate in research
      studies. PARTICIPANTS: The study included 185 patients with CFS, 246 with CF, 111
      with AIM, and 25 with MD. There were 99 HC subjects. MEASURES: The SF-36 and a
      structured psychiatric interview were used. The SF-36 contains 8 subscales:
      physical, emotional, social, and role functioning, body pain, mental health,
      vitality, and general health- and a structured psychiatric interview. RESULTS:
      Performance characteristics (internal reliability coefficients, convergent
      validity) of the SF-36 were excellent. A strikingly consistent pattern was found
      for the physical functioning, role functioning, social functioning, general
      health, and body pain subscales, with the lowest scores in CFS patients,
      intermediate scores in AIM patients, and the highest scores in the HC subjects.
      The CFS patients had significantly lower scores than patients with CF alone on
      the physical functioning (P < or = 0.01), role functioning (P < or = 0.01), and
      body pain (P < or = 0.001) subscales. The emotional functioning and mental health
      scores were worst among those with MD. The presence of fibromyalgia, being
      unemployed, and increasing fatigue severity all were associated with additional
      functional limitations across multiple functional domains, with increasing
      fatigue appearing to have the greatest effect. CONCLUSIONS: The SF-36 is useful
      in assessing functional status in patients with fatiguing illnesses. Patients
      with CFS and CF have marked impairment of their functional status. The severity
      and pattern of impairment as documented by the SF-36 distinguishes patients with
      CFS and CF from those with MD and AIM, and from HC, but does not discriminate
      between CF and CFS.

PMID- 8873507
TI  - Panic disorder in emergency department chest pain patients: prevalence,
      comorbidity, suicidal ideation, and physician recognition.
AB  - PURPOSE: To establish the prevalence of panic disorder in emergency department
      (ED) chest pain patients; compare psychological distress and recent suicidal
      ideation in panic and non-panic disorder patients; assess psychiatric and cardiac
      comorbidity; and examine physician recognition of this disorder. DESIGN: Cross
      sectional survey (for psychiatric data). Prospective evaluation of patient
      discharge diagnoses and physician recognition of panic disorder. SETTING: The
      ambulatory ED of a major teaching hospital specializing in cardiac care located
      in Montreal, Canada. SUBJECTS: Four hundred and forty-one consenting, consecutive
      patients consulting the ED with a chief complaint of chest pain. PRIMARY OUTCOME
      MEASURE: Psychiatric diagnoses (AXIS I). Psychological and pain test scores,
      discharge diagnoses, and cardiac history. RESULTS: Approximately 25% (108/441) of
      chest pain patients met DSM-III-R criteria for panic disorder. Panic disorder
      patients displayed significantly higher panic-agoraphobia, anxiety, depression,
      and pain scores than non-panic disorder patients (P < 0.01). Twenty-five percent
      of panic disorder patients had thoughts of killing themselves in the week
      preceding their ED visit compared with 5% of the patients without this disorder
      (P = 0.0001) even when controlling for co-existing major depression. Fifty-seven
      percent (62/108) panic disorder patients also met criteria for one or more
      current AXIS I disorder. Although 44% (47/108) of the panic disorder patients had
      a prior documented history of coronary artery disease (CAD), 80% had atypical or
      nonanginal chest pain and 75% were discharged with a "noncardiac pain" diagnosis.
      Ninety-eight percent of the panic patients were not recognized by attending ED
      cardiologists. CONCLUSIONS: Panic disorder is a significantly distressful
      condition highly prevalent in ED chest pain patients that is rarely recognized by
      physicians. Nonrecognition may lead to mismanagement of a significant group of
      distressed patients with or without coronary artery disease.

PMID- 8873508
TI  - Anticardiolipin antibodies and acute myocardial infarction in non-systemic lupus
      erythmatosus patients: a controlled prospective study.
AB  - PURPOSE: To examine the prevalence of anticardiolipin antibodies (ACLA) in
      relatively young patients with acute myocardial infarction (MI) and their role in
      subsequent coronary and thromboembolic events in the post-MI period. PATIENTS AND
      METHODS: In 124 relatively young survivors (aged 65 or younger) of acute MI, ACLA
      were measured in a controlled prospective study on admission and 3 months later.
      Myocardial reinfarction and thromboembolic events during a mean follow-up period
      of 19 +/- 3 months were diagnosed by standard tests. RESULTS: Seventeen (14%) of
      the 124 patients were ACLA positive (either IgM or IgG) upon admission compared
      with 2 out of 76 (3%) of the control group matched for age and coronary risk
      factors (P < 0.01). The levels of ACLA remained unchanged in all but 1 patient 3
      months later. During the follow-up period the rate of thromboembolic events and
      myocardial reinfarction was significantly higher in the ACLA-positive patients as
      compared with the ACLA-negative group: 41% versus 4% (P < 0.0001) and 35% versus
      10% (P < 0.05), respectively. Using logistic regression, high titer of ACLA was
      found to be the only independent risk factor for subsequent thromboembolic events
      or myocardial reinfarction after acute MI. CONCLUSIONS: High prevalence of ACLA
      was found in relatively young survivors of acute MI. The presence of ACLA is a
      marker for increased risk of subsequent myocardial reinfarction and
      thromboembolic events after acute MI.

PMID- 8873509
TI  - Clinical relevance of elevated serum thrombomodulin and soluble E-selectin in
      patients with Wegener's granulomatosis and other systemic vasculitides.
AB  - PURPOSE: Vascular injury plays an important pathophysiological role in
      vasculitis. Soluble serum thrombomodulin (sTM), a promising marker of endothelial
      cell injury, is released into the circulating blood following cell damage and was
      therefore investigated as a parameter of disease activity in patients with
      Wegener's granulomatosis (WG) and various other vasculitides. PATIENTS AND
      METHODS: One hundred and ninety-seven sera of 102 patients with histologically
      proven WG of different disease activity and 41 sera of patients with other
      vasculitides at their active stage were investigated (12 Takayasu arteritis [TA],
      7 giant cell arteritis [GCA], 10 polyarteritis nodosa [PAN], 12 Behcet's disease
      [BD]). The sera were examined for the levels of sTM and sE-selectin (CD62E) by
      enzyme-linked immunosorbent assay (ELISA) and for the presence of classical anti
      neutrophil cytoplasmic antibodies (cANCA) by indirect immunofluorescence (IIF).
      The disease activity was evaluated according to the clinical symptoms and organ
      involvement. RESULTS: A significant increase of sTM levels compared with control
      values (26 +/- 2 ng/ml) was found in active WG, TA, GCA, PAN, and BD: limited
      active WG: 63 +/- ng/ml; generalized active WG: 119 +/- 15 ng/ml; limited WG,
      partial remission: 60 +/- 5 ng/ml; generalized WG, partial remission: 75 +/- 7
      ng/ml; active TA: 36 +/-; active GCA: 36 +/- 4 ng/ml, active PAN: 33 +/- 2 ng/ml,
      active BD: 40 +/- 4 ng/ml. Limited and generalized WG in complete remission did
      not have elevated levels of sTM. sTM values closely reflected relapses and
      therapy-induced remissions of WG. Elevated cANCA titers were correlated as well
      with the disease activity in WG but more weakly than sTM levels. In contrast, sE
      selectin values were not significantly correlated with the disease activity and
      the course of disease. CONCLUSIONS: sTM is a promising serological marker of
      disease activity and progression in active limited and generalized WG and other
      vasculitides reflecting the degree of endothelial cell damage. sTM might prove to
      be a clinically useful marker for therapeutic considerations.

PMID- 8873510
TI  - The premortem recognition of systemic senile amyloidosis with cardiac
      involvement.
AB  - PURPOSE: To recognize systemic senile amyloidosis involving the heart and to
      determine outcome. PATIENTS AND METHODS: All patients with the diagnosis of
      amyloidosis at the Mayo Clinic from January 1, 1984 through May 1, 1992, were
      reviewed. Amyloid was confirmed histologically by sulfated alcian blue and
      alkaline Congo red staining. The labeled streptavidin-biotin immunoperoxidase
      method was used with antisera against A kappa, A lambda, AA, transthyretin, and
      beta 2-microglobulin. Anti-P-component and antisera to albumin were used as
      controls. Chest radiographs, electrocardiograms, transthoracic echocardiograms,
      and cardiac catheterization data of all patients were reviewed. Serum and urine
      were examined with immunoelectrophoresis and immunofixation for the presence of a
      monoclonal protein. Lymphocyte DNA was examined for transthyretin mutations
      associated with familial amyloidosis. RESULTS: We identified 18 patients with
      myocardial tissue that stained positive for amyloid with sulfated alcian blue and
      Congo red and with transthyretin antisera. Congestive heart failure was present
      at diagnosis in 17 of the 18 patients. Atrial fibrillation was found in 11
      patients. No monoclonal protein was found in the serum or urine. The
      echocardiographic findings were consistent with infiltrative cardiomyopathy due
      to amyloidosis in 16 patients. Right heart pressures were elevated in all 7
      patients who had right-side heart catheterization. No transthyretin mutations
      were found in the leukocyte DNA from 12 patients. The actuarial median survival
      was 5 years; in contrast, the median survival was 5.4 months in 147 patients with
      primary amyloidosis (AL) who presented with congestive heart failure. CONCLUSION:
      Patients with cardiac amyloid and no monoclonal protein in the serum or urine
      must have immunohistochemical staining for kappa and lambda light chains and
      transthyretin to distinguish between systemic senile amyloidosis, familial
      amyloidosis, and AL. Patients with systemic senile amyloidosis should not be
      treated with alkylating agents. Their survival is much longer than that of
      patients with AL (60 versus 5.4 months).

PMID- 8873511
TI  - Kikuchi-Fujimoto disease: a benign cause of fever and lymphadenopathy.
AB  - PURPOSE: To describe 6 cases of Kikuchi-Fujimoto disease and to review the
      literature. PATIENTS AND METHODS: Review of 6 patients with biopsy-proven Kikuchi
      Fujimoto disease detected at a university hospital over a 5-year period. RESULTS:
      Six patients presented with localized, mild lymph node enlargement. In 3 cases,
      dramatic fever, chills, weight loss and systemic complaints were present. These
      features prompted prolonged antibiotic therapy and extensive evaluations of fever
      of unknown origin before the diagnosis was made by biopsy of the minimally
      enlarged lymph nodes. The 3 remaining patients were otherwise asymptomatic and
      well. All 6 subjects recovered without specific therapy. CONCLUSIONS: Kikuchi
      Fujimoto disease is a recently described cause of benign, self-limited
      lymphadenopathy that is easily confused histologically and clinically with
      lymphoma and systemic lupus erythematosis. Clinicians and pathologists must be
      aware of this condition. Although it is an uncommon cause of fever of unknown
      origin, early recognition of KFD will minimize potentially harmful and
      unnecessary evaluations and treatments.

PMID- 8873512
TI  - Clinical significance of the FV:Q506 mutation in unselected oncology patients.
AB  - PURPOSE: A common germline mutation in the factor V gene (FV:Q506) has been
      associated with hypercoagulability in families with heritable predisposition to
      thrombosis. We examined the prevalence and clinical significance of the FV:Q506
      mutation in cancer patients. PATIENTS AND METHODS: We performed a retrospective
      cohort study by examining 353 consecutive, unselected patients in a general
      hematology/oncology clinic. We ascertained risk factors, obtained the clinical
      clotting history, and determined the heterozygous or homozygous presence of the
      FV:Q506 allele for each patient. RESULTS: We detected a germline mutation in 5.4%
      (19 of 353) of patients, of whom 18 were heterozygous and 1 was homozygous for
      the FV:Q506 mutant allele. In 17 of 18 heterozygous patients, there was no
      history of venous thrombosis or catheter-associated thrombosis. These
      asymptomatic patients included 13 patients who had been diagnosed with cancer or
      leukemia for a mean of 66.2 months (median 69) and had received a variety of
      local and systemic treatments. In contrast, 1 of 18 heterozygous and 1 of 1
      homozygous patients had developed deep vein thrombosis that was associated,
      respectively, with either recurrent thrombotic events or a strong family history
      for pulmonary embolus. CONCLUSIONS: Routine screening for the FV:Q506 mutation in
      cancer patients without a personal or family history for venous thrombosis is not
      helpful in guiding management. In contrast, an episode of venous thrombosis in a
      patient with a mutant germline FV:Q506 allele was associated with recurrent
      thrombotic events. These findings suggest that patients heterozygous for the
      FV:Q506 allele may require an independent "susceptibility" element to manifest a
      venous hypercoagulable state. In addition, only 2 of 25 clinic patients with a
      venous clot carried the FV:Q506 allele suggesting this genetic defect plays a
      minor role in the hypercoagulable state of cancer.

PMID- 8873513
TI  - The management of atrial fibrillation.
AB  - Atrial fibrillation affects approximately one million persons in the United
      States, making it the most common cardiac arrhythmia seen in clinical practice.
      Its prevalence increases with age, and occurs in up to 10% of the population in
      the eighth decade of life. Unlike coronary heart disease, atrial fibrillation
      affects men and women approximately equally and, in an increasingly elderly
      population, will become an increasing burden to the health care system. The
      management of atrial fibrillation has undergone significant change in recent
      years. Large randomized controlled trials have shown that anticoagulation
      markedly reduces the risk of stroke, and a number of new antiarrhythmic agents
      are available for the restoration and maintenance of sinus rhythm. Furthermore,
      physicians have become more aware of the potential proarrhythmic side effects of
      all antiarrhythmic drugs. Finally, new procedures such as radiofrequency ablation
      of the atrioventricular junction and permanent pacing are playing increasing
      roles in the management of this arrhythmia. In this review, the identification of
      underlying causes and/or precipitating factors of atrial fibrillation, methods to
      control the ventricular response with atrioventricular nodal blocking drugs, the
      questions of whether restoration of sinus rhythm is a possible or desirable goal
      and how best to maintain sinus rhythm, should sinus rhythm be restored, and the
      importance of long-term anticoagulation with warfarin or antiplatelet therapy
      with aspirin are discussed.

PMID- 8873514
TI  - Cost-effectiveness of screening for detection of small hepatocellular carcinoma
      in western patients with Child-Pugh class A cirrhosis.
AB  - BACKGROUND AND AIM: The incidence of hepatocellular carcinoma is increased in
      patients with cirrhosis. Therefore, surveillance for detection of small tumors
      has been proposed. The aim of this study was to determine the clinical and
      economical effects of screening for small hepatocellular carcinoma in Western
      patients with Child-Pugh class A cirrhosis. METHODS: Based on a decision analysis
      model representing the natural history of cirrhosis and the continuing risk of
      developing cancer, we compared a strategy of performing ultrasound and alpha
      fetoprotein dosage every 6 months with a strategy of seeking tumors only if they
      are clinically suspected. In both strategies, partial hepatectomy was performed
      for patients with compensated cirrhosis and diagnosed with resectable tumors. We
      did not consider orthotopic liver transplantation as a therapeutic option. Data
      were drawn from MEDLINE search. RESULTS: For most patients seen in the daily
      practice, screening provides negligible benefits in life expectancy (< 3 months),
      even when the incidence of cancer is high (6% per year), and despite our choice
      of consistent biases in favor of screening. The cost-effectiveness ratios of
      systematic surveillance range between $48,000 and $284,000 for each additional
      life-year gained, more than other common medical practices. However, for a
      minority of patients with a predicted cirrhosis-related survival rate above 80%
      at 5 years (the "ideal" candidates) screening may increase mean life expectancy
      by 3 to 9 months depending on age, cancer incidence (1.5% to 6% per year), and
      survival rate after surgery (40% to 60% at 3 years). In this clinical setting,
      the cost-effectiveness ratios range between $26,000 and $55,000 for each
      additional life-year gained. CONCLUSIONS: For most patients with cirrhosis seen
      in the daily practice, biannual screening to detect symptomless tumors accessible
      to surgical resection provides negligible benefit in life expectancy. In
      addition, the cost-effectiveness ratios incurred by this strategy is more
      important than that of many current medical practices. On the other hand, for
      well-targeted patients with the longest reported cirrhosis-related survival rate,
      screening may substantially increase mean life expectancy, at lower costs.
      Careful selection of these patients with a favorable cirrhosis-related prognosis
      requires further studies.

PMID- 8873515
TI  - The substance-using human immunodeficiency virus patient: approaches to
      outpatient management.
AB  - Individuals with a substance use disorder who are infected with human
      immunodeficiency virus (HIV) provide physicians with challenging issues for both
      medical management and drug treatment. Using a case presentation format, we
      present an overview of some of the major issues involved in delivering effective
      primary care for these individuals. A detailed medical and substance use history
      is critical to sort common complaints that can be seen both in HIV infection and
      with drug use. Physicians must be able to recognize withdrawal syndromes and
      differentiate those signs and symptoms that may be attributed to specific drugs.
      A two-phase model of drug abuse treatment takes into account both detoxification
      and maintenance of abstinence. Primary care physicians should be able to initiate
      the process of substance abuse treatment and refer the patient to appropriate
      substance abuse programs when necessary. Pharmacological approaches to long-term
      abstinence with heroin addiction include methadone, LAAM, and naltrexone. While
      clinically challenging, HIV-infected substance users can be successfully managed
      using the general principles of primary care.

PMID- 8873516
TI  - Moderate and transient transfusion-associated cutaneous graft-versus-host disease
      in a child infected by human immunodeficiency virus.

PMID- 8873517
TI  - Treatment of inherited coagulation disorders.

PMID- 8873518
TI  - A cost-minimization analysis of laparoscopic cholecystectomy versus open
      cholecystectomy.
AB  - BACKGROUND: Earlier economic analyses have evaluated charges but not costs, and
      have not considered the cost of production losses associated with open and
      laparoscopic cholecystectomy. This study attempted to accomplish an economic
      evaluation of open versus laparoscopic cholecystectomy from the point of view of
      society. METHODS: A cost-minimization analysis, using a clinical decision model,
      was performed. The data used were taken from different clinical studies, Swedish
      national registers, local patient statistics, and hospital accounting systems.
      The direct and indirect costs were measured. RESULTS: Laparoscopic
      cholecystectomy resulted in cost savings per patient amounting to about 2,400 SEK
      (as of 31 August 1994, Pound = 11.90 SEK; $1 = 7.76 SEK) compared with open
      surgery. CONCLUSIONS: From the point of view of society, laparoscopic
      cholecystectomy was a cost-saving strategy if at least 68 patients were operated
      on yearly. However, with regard to hospital costs, open cholecystectomy was less
      expensive than laparoscopic cholecystectomy.

PMID- 8873519
TI  - Long-term results of unilateral neck exploration for preoperatively localized
      nonfamilial parathyroid adenomas.
AB  - BACKGROUND: Unilateral neck exploration for sporadic parathyroid adenomas remains
      a contentious policy. The morbidity is lower than for bilateral surgery, but the
      long-term outcome may be inferior. METHODS: The results of a policy of unilateral
      neck exploration for primary hyperparathyroidism based on preoperative
      localization are reviewed. RESULTS: Over a 10-year period, 89 patients were
      operated on, 57 undergoing unilateral neck exploration. Unilateral neck
      exploration significantly reduced operative time (P < 0.0001) and postoperative
      hypocalcaemia (P = 0.021). Over a mean biochemical follow-up of 38 months,
      recurrent hypercalcaemia occurred in 6% of patients, including 3.5% of those
      undergoing unilateral neck exploration, an additional 10% of patients were
      normocalcaemic with an inappropriately elevated parathormone level. CONCLUSIONS:
      A policy of unilateral neck exploration can achieve comparable long-term results
      to more extensive bilateral surgery.

PMID- 8873520
TI  - The tension-free hernioplasty in a randomized trial.
AB  - BACKGROUND: The tension-free hernioplasty as introduced by Lichtenstein has
      gained increasing acceptance during the last decade although the technique has
      not been evaluated in a randomized trial. METHODS: This randomized study compares
      the 2-year follow-up results after 102 tension-free hernioplasties with
      implantation of a prolene mesh in all groin hernias to 53 Cooper ligament repairs
      in direct hernias and 53 abdominal ring repairs in indirect hernias. RESULTS:
      After tension-free repairs five hernias recurred (5%), and after either Cooper
      ligament or abdominal ring repair, 16 recurrences were found (15%) (P = 0.025).
      No indirect hernias recurred after a tension-free repair; 2 recurred after
      abdominal ring repair (4%; NS). The recurrence rate after tension-free repairs
      for primary direct inguinal hernias was 7% as compared with 30% after Cooper
      ligament repair (P = 0.0081). No difference in complication rate between the
      tested methods was found. CONCLUSION: Recurrence rate is reduced to one-third
      after tension-free herniotomies as compared with the conventionel herniotomies
      without increase in complication rate.

PMID- 8873521
TI  - Causes of death among patients surviving at least one year following splenectomy.
AB  - BACKGROUND: To assess the mortality (mostly long-term sequelae) of patients
      undergoing splenectomy, we carried out a population-based study in Sweden.
      METHODS: Using the unique personal identification number assigned to each Swedish
      resident, we linked centralized hospitalization records with nationwide mortality
      data. After initially assessing risks within the first 12 months after
      splenectomy, we excluded deaths during the first year and computed standardized
      mortality ratios (SMRs) for 1,297 patients splenectomized for external trauma and
      991 surgically treated for nonmalignant conditions of adjacent organs who were
      alive at 12 months following surgery. The general Swedish population was used as
      the comparison. RESULTS: Both men and women undergoing splenectomy for external
      trauma had a 1.6-fold (SMR = 1.6) significantly elevated mortality risk, due
      mainly to circulatory diseases (particularly thromboembolism), alcoholism,
      digestive disorders, and external causes. Men also had a 28-fold increased
      mortality from septicemia and an excess of liver cirrhosis (mostly alcohol
      related). Patients of both genders splenectomized for nonmalignant conditions had
      small but significantly elevated mortality overall (SMR = 1.4 to 1.5) reflecting
      excess risks for malignancies, diseases of blood-forming organs, external causes,
      and circulatory, respiratory, and digestive disorders. In addition, men had
      increased mortality from thromboembolism and pneumonia while women experienced
      elevated risks from septicemia. CONCLUSION: The excess mortality resulted from
      functional postsplenectomy defects (including sepsis and thromboembolism),
      behaviors increasing risk of traumatic splenic injury (eg, alcoholism), damage to
      other organs from the external trauma (eg, traumatic injury to the central
      nervous system/spinal cord), or the same or recurrent nonmalignant conditions for
      which surgery was performed (eg, gastric and duodenal ulcers).

PMID- 8873522
TI  - Inadvertent perforation of the rectum during abdominoperineal resection.
AB  - BACKGROUND: Intraoperative inadvertent perforation of the rectum is a potentially
      avoidable complication of abdominoperineal resection (APR). Although widely
      thought to be detrimental, the impact of inadvertent perforation on outcome has
      not been conclusively determined, especially after controlling for potential
      confounding variables. The objective of this study was to determine if
      inadvertent perforation of the rectum during APR for rectal cancer is an
      independent risk factor for the adverse outcomes of local recurrence and/or
      death. METHODS: This retrospective cohort study included all patients who
      underwent APR for primary adenocarcinoma of the rectum at a single teaching
      hospital from 1980 to 1990. Data were obtained regarding patient demographics,
      presence of inadvertent perforation, histopathological characteristics, adjuvant
      therapy, local recurrence, and survival. RESULTS: Of 178 patients included in the
      study, 42 (24%) had inadvertent perforation. By univariate analysis, local
      recurrence was significantly higher in the perforated group than the
      nonperforated group (54% vs 17%; P < 0.001). Similarly, 5-year survival was
      significantly decreased with inadvertent perforation (29% vs 59%; P = 0.003).
      Multivariate analysis controlling for stage, grade, age, sex, and adjuvant
      therapy showed inadvertent perforation to be an independent risk factor for both
      increased local recurrence and decreased 5-year survival (Hazard Ratio for each
      model). CONCLUSIONS: Inadvertent perforation of the rectum during APR is
      associated with increased local recurrence and decreased 5-year survival. The
      detrimental implications of inadvertent perforation during APR mandates
      meticulous avoidance.

PMID- 8873523
TI  - Prospective, randomized evaluation of midline fascial closure in gastric
      bariatric operations.
AB  - BACKGROUND: Severe obesity is cited as a major risk factor for fascial wound
      dehisence and late incisional hernia after major abdominal surgery. The purpose
      of this study was to prospectively compare two methods of closure of the linea
      alba after gastric restrictive operations performed for treatment of morbid
      obesity. METHODS: During a 6-year period 229 patients were randomized to have
      closure of the midline fascia using either a double-stranded #1 PDS suture placed
      in a continuous fashion or #1 Ethibond suture placed using an interrupted figure
      eight technique. RESULTS: Two of 109 patients who had closure with Ethibond
      suffered an acute dehiscence of the midline fascia vs no cases of fascial
      dehiscence in the PDS group. There were no wound infections in either group.
      There were 20 late incisional hernias (18%) in the Ethibond group vs 11 late
      hernias (10%) in the PDS group (P < or = 0.04). Mean postoperative follow-up time
      for all patients was 29.4 months. The cost of suture material and the time
      required to completely close the linea alba were also calculated for each group.
      The mean closure time in the Ethibond group was 13.3 vs 9.1 minutes in the PDS
      group (P < 0.0001). Although the cost per suture pack of #1 PDS was $4.63 vs
      $1.76 per pack for #1 Ethibond, the mean cost of sutures per patient was $4.81
      for PDS vs $11.09 for Ethibond. CONCLUSIONS: We conclude that #1 PDS placed in a
      continuous fashion provides a more secure and cost-effective closure of the
      midline fascia in morbidly obese patients than #1 Ethibond placed using an
      interrupted figure-eight technique.

PMID- 8873524
TI  - Postoperative abdominal wall defects with enterocutaneous fistulae.
AB  - BACKGROUND: Abdominal wall dehiscence with an associated enterocutaneous fistula
      is a surgical complication with high morbidity and mortality. Management of the
      abdominal wall defect is complicated by the continued emergence of liquid bowel
      contents. PATIENTS AND METHODS: Large abdominal wall wounds of 10 patients with
      postoperative abdominal wall dehiscence and active enterocutaneous fistulae were
      managed with early skin grafting directly onto the granulated abdominal viscera.
      RESULTS: Skin graft take averaged 93 +/- 12%, and there were no perioperative
      complications related to the skin grafting procedure. Overall mortality was 1 out
      of 10 patients. Enterocutaneous fistula output did not prove overly injurious to
      the skin grafts. Wound care was simplified in all but 1 patient with fitting of
      an ostomy appliance. CONCLUSION: Temporary abdominal wall wound closure with skin
      grafts improved patient comfort and simplified wound care in a staged
      reconstructive approach to this surgical complication.

PMID- 8873525
TI  - The ileocecal reservoir for rectal replacement in complicated radiation
      proctitis.
AB  - BACKGROUND/AIMS: Total rectal resection is the radical treatment method for
      radiation proctitis complications. Park's straight colo-anal reconstruction to
      replace the rectum often impairs anal continence, increases stool frequency, and
      causes imperative urgency. We developed and assessed a colo-anal reconstruction
      (ileocecal reservoir) after resection of radiation-damaged rectum. METHODS: An
      ileocecal segment was isolated on its lymphovascular pedicel, rotated
      counterclockwise, and reanastomosed at the dentate line. This provided a
      neorectal segment with intact intrinsic and extrinsic nerve and lymphovascular
      supply. We evaluated the safety, defecation quality, and anorectal function of
      this neorectum in two radiation-injured patients when compared with 15 patients
      after total mesorectal excision without radiation damage. RESULTS: No
      perioperative morbidity related to this technique was observed. Neorectal
      patients showed good defecation quality with maximal tolerable volumes,
      compliances, and anal manometry comparable with patients without radiation
      injury. CONCLUSIONS: This rectal replacement technique permits good defecation
      quality and excellent anorectal function.

PMID- 8873526
TI  - Endotoxin inhibitor prevents sepsis-induced alterations in intestinal ion
      transport.
AB  - BACKGROUND: The intestine is a target of septic insult. The aims of this study
      were to characterize sepsis-induced alterations in intestinal ion transport and
      to determine the role endotoxin plays in mediating these changes. METHODS: Rats
      underwent cecal manipulation alone (control), cecal ligation and puncture (CLP),
      or CLP plus intraperitoneal injection of 0.2 mg of a recently synthesized
      endotoxin inhibitor. At 24 hours, distal ileum was harvested, and transport
      parameters were determined. RESULTS: Cecal ligation and puncture produced a
      significant increase in short-circuit current (Isc) that was attributable to the
      induction of chloride secretion. There were no alterations in transepithelial
      resistance or fluxes of mannitol and sodium. The sepsis-induced increase in Isc
      was prevented by administration of the endotoxin inhibitor. CONCLUSIONS: In this
      model of sepsis, the primary alteration in ileal ion transport is an induction of
      electrogenic chloride secretion. Endotoxin inhibition may represent a strategy
      for prophylaxis against the intestinal effects of sepsis.

PMID- 8873527
TI  - Preservation of normal gastric emptying following gastric surgery by use of a
      muscle bridge.
AB  - BACKGROUND: Maintenance of descending antral intramural pathways may be important
      in normal functioning of the pylorus after pylorus-preserving gastrectomy.
      METHODS: We examined the effect of a 1-cm bridge of muscle as a means of
      maintaining pyloric connection to antral intramural motor control pathways in 10
      pigs. Antropyloroduodenal pressures and transpyloric flow were measured during
      gastric emptying of saline before and after either total or subtotal transection
      and reanastomosis of antrum. RESULTS: Complete antral transection shortened the
      time interval between antral and subsequent pyloric lumen occlusion,
      significantly reducing total gastric emptying and volume of transpyloric flow
      pulses. Subtotal transection maintained pre-transection timing and was associated
      with normal patterns of transpyloric flow and emptying. CONCLUSIONS: Our results
      indicate that a muscle bridge is capable of maintaining normal gastric emptying
      and the coordination of antral with pyloric contractions. We propose that
      antropyloric coordination is maintained by transmission of neural signals through
      the muscle bridge.

PMID- 8873528
TI  - CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in
      pancreatic cancer.
AB  - PURPOSE: This study examines the changes of serum levels of CA 19-9 in patients
      with pancreatic cancer following neoadjuvant irradiation and chemotherapy to
      define the potential role of this tumor marker in preoperative management of
      these patients. MATERIALS AND METHODS: Serum CA 19-9 levels were measured in 42
      patients before receiving external beam irradiation with concurrent 5
      fluorouracil in preparation for laparotomy and Whipple procedure or
      intraoperative irradiation (IORT). The CA 19-9 levels were determined again after
      irradiation, and changes were correlated with findings of restaging computed
      tomography (CT) scan and laparotomy. RESULTS: Following preoperative irradiation,
      10 patients (24%) experienced an increase in CA 19-9 levels whereas 29 patients
      (69%) showed a decrease in CA 19-9. There was no change in the CA 19-9 levels of
      3 patients (7%) after treatment. Of the 10 patients with increased CA 19-9 levels
      after irradiation, 9 (90%) had developed distant metastases or local tumor
      progression as determined by restaging CT scan or at laparotomy. In contrast,
      only 6 of 29 patients (21%) with declining CA 19-9 levels after irradiation
      demonstrated metastases or local tumor progression on restaging CT scan or at
      laparotomy. The correlation of CA 19-9 increase or decrease with disease
      progression or control, respectively, was statistically significant (P = 0.009).
      CONCLUSIONS: Serum CA 19-9 levels may rise or fall during neoadjuvant therapy. A
      rising CA 19-9 reliably indicates cancer progression while a falling CA 19-9
      connotes disease control in the majority of patients. In developing strategies
      for application of neoadjuvant therapy for pancreatic cancer, monitoring of CA 19
      9 appears most useful for the identification of patients who manifest progressive
      tumor growth and metastasis in spite of this treatment.

PMID- 8873529
TI  - The role of laparoscopy in chronic and recurrent abdominal pain.
AB  - BACKGROUND: This study was designed to determine the efficacy of laparoscopy on
      patients with a history of recurrent and chronic abdominal pain longer than 3
      months, of unknown origin. METHODS: From September 1990 to May 1994, we performed
      66 laparoscopic treatments on 59 patients. The assessment of life quality ensured
      the disability score, the McGill pain questionnaire, and the visual analogue pain
      scale, which were completed preoperatively, then on the day of discharge, and
      finally at a mean period follow-up of 75.3 weeks. Laparoscopy provided diagnosis
      on 53 of 59 patients (89.8%). RESULTS: All 66 attempted laparoscopic procedures
      were completed successfully, no conversion to laparotomy was necessary, and no
      postoperative complication occurred. Five out of 59 patients (8.5%) revealed no
      improvement of pain postoperatively, and 6 out of 56 (10.7%) still suffer from
      pain at the time of the follow-up. CONCLUSIONS: The pain assessment and
      disability score was statistically significant postoperatively and at the time of
      the follow-up in relation to the preoperative score.

PMID- 8873530
TI  - Vascular endostapler as aid to hepatic vein control during hepatic resections.
AB  - Significant hemorrhage during hepatic resections for malignancies can result in
      increased mortality due to liver failure or acute blood loss. Massive hemorrhage
      is often related to loss of control or injury to the hepatic veins or inferior
      vena cava. Prevention or reduction of intraoperative blood loss, through improved
      surgical techniques and increased operator experience, can significantly reduce
      postoperative morbidity and mortality. Although the use of continuous or
      intermittent clamping of the portal triad structures (Pringle maneuver) has
      reduced the incidence of bleeding during hepatic transections, the hepatic vein
      ligation step of liver resections continues to be a possible source of major
      blood loss. Because of its safety, rapidity, and ease of application, the EndoGIA
      30V vascular stapler is presented as an efficient means for controlling and
      dividing the major hepatic veins. In skilled hands, this stapling device can
      contribute to a reduction in incidence and risk of major intraoperative bleeding
      during hepatectomy. The critical factor to ensuring postoperative morbidity
      reduction, however, is the surgeon's experience in major hepatic resection
      procedures.

PMID- 8873531
TI  - Video-assisted, retroperitoneal approach for abdominal aortic aneurysm exclusion.
AB  - Abdominal aortic aneurysm (AAA) repair is a common procedure associated with
      significant morbidity and mortality. Although attempts have been made to reduce
      operative risk in patients with significant comorbid disease by combining
      aneurysm exclusion with axillofemoral bypass, the morbidity is not greatly
      reduced when the standard operative approach is required for exclusion. The
      authors describe a technique for staple exclusion of AAA using a minimally
      invasive, video-assisted retroperitoneal approach.

PMID- 8873532
TI  - Does volume of clinical experience affect performance of clinical clerks on
      surgery exit examinations?
AB  - BACKGROUND: Controversy persists over the educational value of student clerkship
      clinical activities. METHODS: Students (109) from the class of 1995 recorded
      their clinical experiences in a logbook during their surgical clerkship at one of
      four affiliated teaching hospitals. The influence of clinical experience on
      examination scores and on correlations between prerotation and postrotation
      examination performance was determined. RESULTS: Between sites, marked variation
      in clinical experience was observed but postrotation scores were similar. High
      volume experience in emergency admissions and feedback was associated with better
      objective structured clinical examination (OSCE) performance, but high-volume
      outpatient clinic experience was associated with less satisfactory OSCE
      performance. Correlations between prerotation examination performance and the
      OSCE was increased by feedback on emergency and elective admissions, in a
      positive and negative direction, respectively. CONCLUSIONS: These data show that
      surgical clerks' clinical skills were enhanced by an increased volume of some but
      not all clinical experiences and that feedback does not necessarily enhance
      performance. These data suggest that both the volume of clinical experience and
      the quality of feedback should be carefully monitored by surgical clerkship
      directors.

PMID- 8873533
TI  - The impact of gender on the choice of surgery as a career.
AB  - BACKGROUND: The objective of the survey was to examine factors affecting career
      choice by medical students. METHODS: A questionnaire was distributed to the 245
      fourth-year students at the University of Toronto, sampling qualities of
      importance in specialties, the importance of role models, attitudes toward
      surgery, and specialty match results. RESULTS: There was a 69% return rate. Males
      were more likely to choose a surgical career than were females (27% versus 10%,
      respectively; P = 0.01). Males were more likely to identify technical challenge,
      earning potential, and prestige (P < 0.01) whereas females were more likely to
      identify residency conditions, part-time work, and parental leave availability as
      important qualities in a specialty (P < 0.01). Females were less likely to take
      surgical electives (P < 0.001) and more likely to identify a lack of role models
      (P < 0.003). Students agreed that surgeons have rewarding careers (79%) and earn
      more (64%); however, they do not agree that surgeons enjoy spending time with
      patients (10%) or have rewarding family lives (5%). CONCLUSIONS: Fewer females
      than males were found to consider or choose a surgical career, possibly due to
      differences in qualities of importance in specialties, availability of role
      models, and exposure through electives.

PMID- 8873534
TI  - Laparoscopic skills enhancement.
AB  - BACKGROUND: Laparoscopy requires a unique subset of surgical skills that, for the
      inexperienced, can significantly delay the development of basic operative skills.
      We hypothesized that learning laparoscopic suturing and knot tying would improve
      laparoscopic skills. METHODS: A laparoscopic training seminar for junior surgical
      residents was established to test this hypothesis. Emphasis was placed on
      laparoscopic knot tying and suturing. Skills were assessed at the beginning and
      the end of the course. RESULTS: All residents showed significant improvement.
      Dominant and nondominant hand skills improved by 30.2% and 26.9%, respectively.
      Two-handed skills improved by 58.6% and 30.1%. Overall scores improved by 28.9%.
      CONCLUSIONS: A structured laparoscopic skills course stressing knot tying and
      suturing is an effective way to develop dexterity and significantly improve the
      performance of laparoscopic tasks. These improvements can be accomplished in a
      cost-effective curriculum that should enhance the surgical education of residents
      and speed the acquisition of competent operative skills.

PMID- 8873535
TI  - Effect of patient position upon success in placing central venous catheters.
AB  - BACKGROUND: There is little consensus regarding the most efficient or the safest
      method by which to place a central venous catheter (CVC). METHODS: A single house
      officer prospectively evaluated 140 patients for whom he was requested to place
      CVCs. One hundred and eight patients participated in a randomized study of
      positioning. Of the 140 patients, 7 had emergency line placement; 105 randomized
      patients undergoing elective CVC placement form the basis for this report (power
      > 80% to detect change of one needle pass between groups). Patient positions were
      termed "bump" (head turned to the contralateral side and a rolled towel placed
      vertically between the scapulas) and "no bump" (head facing forward and no towel
      placed in the back.) RESULTS: Ninety-three of 105 patients had successful
      catheter placement. Catheters were more often successfully introduced in the bump
      group than no bump group (98% versus 83%, P < 0.04). For patients with difficult
      CVC placement (those > 160 pounds, those with a weight-to-height ratio > 29,
      those with previous unsuccessful catheterization), the bump position was superior
      with respect to increased likelihood of venous blood return, decreased likelihood
      of arterial blood return, and increased likelihood of successful catheterization,
      although differences did not reach statistical significance (P < 0.05) in
      individual analyses. Of patients with successful catheterization, 97% had three
      or fewer needle passes. Those with more than three needle passes were less likely
      to have successful catheter placement (P < 0.01), were more likely to have
      arterial blood return (P < 0.01) and pneumothorax (P = 0.12). CONCLUSIONS: The
      bump position improves the likelihood of successful central venous catheter
      placement. No more than three needle passes ought to be attempted.

PMID- 8873536
TI  - Raising the outcome standards for conventional open cholecystectomy.
AB  - BACKGROUND: Postcholecystectomy length of stay declined after the introduction of
      laparoscopy in 1987. Technology deserves some credit for reducing iatrogenic
      trauma. However, the improved outcome primarily resulted from setting higher
      surgical standards. What goals were (and are) achievable with the conventional
      "open" technique? METHODS: One surgeon performed 160 consecutive open
      cholecystectomies from 1983 to 1987. The patients averaged 46 years of age (range
      13 to 100), 62% were female, and 20% presented acutely. Five (3.1%) had common
      bile duct exploration. Each patient was prepared to accept early discharge.
      Prompt ambulation followed minimal tissue handling and use of long-acting local
      anesthesia. Enteral feeding at 300 kcal plus 12 g AAs/ hour began immediately,
      with swallowed air and potential excess removed automatically by efficient more
      proximal aspiration. RESULTS: 160 patients were discharged the next day, 158 of
      160 (99%) without receiving any narcotics. They absorbed (on average) 3,350 kcal
      plus 130 g AAs the initial 8 to 16 hours. Serum branched-chain amino acids (BCAA)
      levels rose above basal within 4 hours. Three patients (1.9%) were readmitted.
      One (0.6%) had a sterile biloma drained percutaneously. A single acute
      cholecystitis patient developed sepsis (0.6%), a subphrenic abscess that resolved
      after drainage. The sole mortality (0.6%) was caused suddenly 27 days
      postoperatively by a pulmonary embolus. CONCLUSIONS: Laparoscopy is a valuable
      surgical tool whose actual incremental benefits are yet to be determined. Shorter
      length of stay after cholecystectomy may primarily reflect the altered
      expectations and overall improved surgical performance associated with this
      innovation.

PMID- 8873537
TI  - Is octreotide a new hope for enterocutaneous and external pancreatic fistulas
      closure?
AB  - BACKGROUND: Octreotide is a long-acting analogue of somatostatin that exhibits
      good subcutaneous absorption. It reduces gastrointestinal and pancreatic
      secretions as well as relaxes the intestinal musculature. It has been
      hypothesized that octreotide could decrease fistula output, thus facilitating
      fluid and electrolytes management and possibly hasten fistula closure. DATA
      SOURCES: Relevant articles were identified from a MEDLINE search of the
      literature. Because of the scarcity of well-designed studies on the use of
      octreotide to promote enterocutaneous and pancreaticocutaneous fistulas closure,
      all case series and controlled trials were reviewed. CONCLUSIONS: Octreotide as
      an adjuvant to standard fistula management diminishes fistula output, but its
      shortening of the time to fistula closure remains to be proven by well-designed
      comparative trials. For recent onset fistulas (less than 8 days old), octreotide
      does not seem better than the recommended management, including parenteral
      nutrition. Octreotide can effectively prevent postoperative complications and
      fistula formation in patients undergoing elective pancreatic resection.

PMID- 8873538
TI  - Use of neuromuscular blocking drugs in scientific investigations involving animal
      subjects. The benefit of the doubt goes to the animal.

PMID- 8873539
TI  - Small, oral dose of clonidine reduces the incidence of intraoperative myocardial
      ischemia in patients having vascular surgery.
AB  - BACKGROUND: Most new perioperative myocardial ischemic episodes occur in the
      absence of hypertension or tachycardia. The ability of alpha 2-adrenoceptor
      agonists to inhibit central sympathetic outflow may benefit patients with
      coronary artery disease by increasing the myocardial oxygen supply and -demand
      ratio. METHODS: A randomized double-blind study design was used in 297 patients
      scheduled to have elective vascular surgical procedures to evaluate the effects
      of 2 micrograms/kg-1 oral clonidine (n = 145) or placebo (n = 152) on the
      incidence of perioperative myocardial ischemic episodes, myocardial infarction,
      and cardiac death. Continuous real-time S-T segment trend analysis (lead II and
      V5) was performed during anesthesia and surgery and correlated with arterial
      blood pressure and heart rate before and during ischemic events. Dose
      requirements for vasoactive and antiischemic drugs to control blood pressure and
      heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta
      adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume
      load were recorded. RESULTS: Administration of clonidine reduced the incidence of
      perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of
      145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the
      number of ischemic episodes per patient did not differ. Nonfatal myocardial
      infarction developed after operation in four patients receiving placebo compared
      with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal
      cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and
      antiischemic drugs did not differ between the groups, but the amount of
      presurgical fluid volume was slightly greater in patients receiving clonidine
      (951 +/- 388 vs. 867 +/- 381 ml; P < 0.03). CONCLUSION: A small oral dose of
      clonidine, given prophylactically, can reduce the incidence of perioperative
      myocardial ischemic episodes without affecting hemodynamic stability in patients
      with suspected or documented coronary artery disease.

PMID- 8873540
TI  - Effect of flumazenil on ventilatory drive during sedation with midazolam and
      alfentanil.
AB  - BACKGROUND: Patients who receive a combination of a benzodiazepine and an opioid
      for conscious sedation are at risk for developing respiratory depression. While
      flumazenil effectively antagonizes the respiratory depression associated with a
      benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and
      an opioid has not been established. This study was designed to determine whether
      flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in
      the presence of an opioid. METHODS: Twelve healthy volunteers completed this
      randomized, double-blind, crossover study. Ventilatory responses to carbon
      dioxide and to isocapnic hypoxia were determined during four treatment phases:
      (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil
      infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting
      of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6
      weeks later to receive the alternate study drug. RESULTS: Alfentanil decreased
      the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/-
      0.19 l.min-1.mmHg-1 (x +/- SE, P < 0.05), and decreased the minute ventilation at
      P(ET)CO2 = 50 mmHg (VE50) from 19.7 +/- 1.2 to 14.8 +/- 0.9l.min-1 (P < 0.05).
      Midazolam further reduced these variables to 0.87 +/- 0.17 l.min-1.mmHg-1 (P <
      0.05) and 11.7 +/- 0.8 l.min-1 (P < 0.05), respectively. With addition of
      flumazenil, slope and VE50 increased to 1.47 +/- 0.37 l.min-1.mmHg-1 (P < 0.05)
      and 16.4 +/- 2.0l.min-1 (P < 0.05); after placebo, the respective values of 1.02
      +/- 0.19 l.min-1.mmHg-1 and 12.5 +/- 1.2 l.min-1 did not differe significantly
      from their values during combined alfentanil and midazolam administration. The
      effect of flumazenil differed significantly from that of placebo (P < 0.05). Both
      the slope and the displacement of the hypoxic ventilatory response, measured at
      P(ET)CO2 = 46 +/- 1 mmHG, were affected similarly, with flumazenil showing a
      significant improvement compared to placebo. CONCLUSIONS: Flumazenil effectively
      reverses the benzodiazepine component of ventilatory depression during combined
      administration of a benzodiazepine and an opioid.

PMID- 8873541
TI  - Reduction of isoflurane minimal alveolar concentration by remifentanil.
AB  - BACKGROUND: Remifentanil is a new micro-specific opioid receptor agonist
      currently under investigation. The interaction between opioids and volatile
      anesthetics is complex. Defining this interaction provides a basis for more
      rational dosing schemes when such combinations are used for anesthesia and allows
      the anesthetic potency of remifentanil relative to other opioids to be
      determined. METHODS: Two centers enrolled a total of 220 patients. Patients were
      randomized to receive a target concentration of remifentanil via a computer
      assisted continuous infusion device of either 0.0, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0,
      16.0, and 32.0 ng/ml initiated before the administration of isoflurane. Patients
      were also stratified by groups 18-30, 31-55, and 56-65 yr. After induction of
      anesthesia with isoflurane the initial patient in each dose group was assigned an
      age-adjusted isoflurane concentration. The isoflurane concentration for each
      subsequent patient was adjusted according to the up/down technique until a
      minimum of 12 patients were enrolled in each group. Arterial blood samples for
      remifentanil whole blood concentrations were obtained. The patient was observed
      for purposeful movement for up to 1 min after skin incision. The minimum alveolar
      concentration (MAC) of isoflurane (0 ng/ml remifentanil group) and MAC reduction
      of isoflurane by remifentanil were determined. RESULTS: The MAC of isoflurane
      alone was 1.3%. Remifentanil caused an exponential reduction in the MAC of
      isoflurane with 1.37 ng/ml remifentanil a 77% reduction and 32 ng/ml a 91%
      reduction of isoflurane MAC. CONCLUSION: The MAC reduction of isoflurane by
      remifentanil is similar to that produced by other opioids. Although remifentanil
      was given at extremely high concentrations in the absence of isoflurane, it did
      not provide adequate anesthesia. A 50% isoflurane MAC reduction is produced by
      1.37 ng/ml remifentanil whole blood concentration compared to previously
      published plasma concentrations of fentanyl of 1.67 ng/ml or sufentanil of 0.14
      ng/ml.

PMID- 8873542
TI  - Dose-response characteristics of spinal bupivacaine in volunteers. Clinical
      implications for ambulatory anesthesia.
AB  - BACKGROUND: Small doses of bupivacaine may be a reasonable choice for spinal
      anesthesia for patients having ambulatory surgery. However, few dose-response
      data are available to guide the selection of reasonable doses of bupivacaine for
      different ambulatory procedures. METHODS: Eight volunteers per group were
      randomized to receive 3.75, 7.5, or 11.25 mg of 0.75% bupivacaine with 8.25%
      dextrose in a double-blind manner. Sensory block was assessed with pinprick,
      transcutaneous electrical stimulation equivalent to surgical incision at the
      ankle, knee, pubis, and umbilicus, and with duration of tolerance to pneumatic
      thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was
      assessed with isometric force dynamometry. Times until recovery from spinal
      anesthesia were recorded. Dose-response relationships were determined by linear
      regressions. Mean (95% confidence intervals) for durations of sensory and motor
      block per milligram of bupivacaine administered were calculated from linear
      regressions. RESULTS: Significant dose-response relationships (P < 0.006) were
      determined for sensory block, motor block, and time until recovery (R from 0.6 to
      0.9). Within the range of doses studied, each additional milligram of bupivacaine
      was associated with an increase in duration of tolerance to transcutaneous
      electrical stimulation of 10 (7 to 13) min, an increase in tolerance to
      tourniquet of 7 (2 to 11) min, an increase in duration of motor block of 8 (5 to
      12) min, and an increase in time until recovery of 21 (17 to 25) min.
      CONCLUSIONS: These dose-response data may guide the selection of reasonable doses
      of bupivacaine for various outpatient procedures, although individual responses
      vary.

PMID- 8873543
TI  - Site(s) mediating sympathetic activation with desflurane.
AB  - BACKGROUND: Three strategies were employed to better define the afferent site(s)
      at which desflurane initiates its neurocirculatory activation. METHODS: Young
      (aged 19-28 yr) healthy volunteers were employed in three separate studies.
      Monitoring included electrocardiography, radial artery blood pressure, and direct
      recordings of sympathetic outflow to skeletal muscle blood vessels by
      microneurography. In each study, anesthesia was established with 2.5 mg/kg
      propofol, and in studies 1 and 2 was maintained with 5.4% desflurane via a double
      lumen tube. In study 1 (n = 7) a double-lumen tube was placed with the bronchial
      cuff just below the vocal cords to selectively give 14.5% desflurane or 2.4%
      isoflurane to the upper airway (via the tracheal lumen) or lower airway (via the
      bronchial lumen). Study 2 (n = 14) consisted of standard placement of a left side
      double-lumen tube to selectively increase the inspired desflurane concentration
      of either right or left lung to 11% while decreasing the inspired concentration
      in the opposite lung to 0%, thereby maintaining constant systemic concentrations
      of desflurane (gas chromatography). Study 3 consisted of lidocaine or placebo
      airway treatment before anesthetic induction and administration of 11% inspired
      desflurane by mask: group A-n = 9, topical and nebulized lidocaine,
      glossopharyngeal and superior laryngeal nerve blocks, and transtracheal
      administration of lidocaine; group B-n = 7, similar treatment as group A with
      placebo (saline); and group C-n = 8, systemic infusions of 2% lidocaine to match
      plasma concentrations of lidocaine in group A. RESULTS: In study 1, significant
      increases in heart rate, mean arterial pressure, and sympathetic neural activity
      (26%, 23%, and 62%, respectively) occurred when desflurane was directed to the
      upper airway. These responses were approximately twofold to sixfold larger when
      desflurane was given to the lower airway (lungs). There were no significant
      increases in these variables when isoflurane was administered to the upper
      airways, and a significant increase in heart rate occurred only when isoflurane
      was delivered to the lower airways. In study 2, separate right or left lung
      increases in desflurane did not change the blood concentration of desflurane or
      sympathetic neural activity but led to significant increases in heart rate (44%)
      and mean arterial pressure (32%). The simultaneous administration of desflurane
      to both lungs increased the millimolar (mM) concentration of desflurane in the
      blood from 1.17 to 2.39 mM and led to increases in sympathetic neural activity
      (750%), heart rate (90%), and mean arterial pressure (63%). In study 3, neither
      regional nor systemic administration of lidocaine reduced the significant
      neurocirculatory activation caused by the rapid increase in the inspired
      concentration of desflurane by mask. CONCLUSIONS: There are sites in the upper
      airway (larynx and above) that respond with sympathetic activation during rapid
      increases in desflurane concentration independent of systemic anesthetic changes.
      These responses, while lesser than those seen with rapid increases to the lung,
      may represent direct irritation of airway mucosa. Heart rate and mean arterial
      pressure responses to desflurane can be initiated by selectively increasing
      concentrations to either right or left lung without altering systemic levels of
      desflurane. From this it is inferred that there are sites within the lungs,
      separate from systemic sites, that mediate this response. Neither systemic
      lidocaine nor attempted blockade of upper airway sites with cranial nerve blocks
      combined with topical lidocaine was effective in attenuating the neurocirculatory
      activation associated with desflurane.

PMID- 8873544
TI  - Sympathetic nervous system does not mediate reflex pupillary dilation during
      desflurane anesthesia.
AB  - BACKGROUND: Pupil size is determined by an interaction between the sympathetic
      and parasympathetic divisions of the autonomic nervous system. Noxious
      stimulation dilates the pupil in both unanesthetized and anesthetized humans. In
      the absence of anesthesia, dilation is primarily mediated by the sympathetic
      nervous system. In contrast, pupillary dilation in cats given barbiturate or
      cloralose anesthesia is mediated solely by inhibition of the midbrain
      parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils
      during anesthesia in humans remains unknown. Accordingly, the authors tested the
      hypothesis that the pupillary dilation in response to noxious stimulation during
      desflurane anesthesia is primarily a parasympathetic reflex. METHODS: In six
      volunteers, the alpha-I adrenergic receptors of the iris musculature were blocked
      by unilateral administration of topical dapiprazole; six other volunteers were
      given unilateral topical tropicamide to block the muscarinic receptors in the
      iris. Desflurane anesthesia was subsequently induced in all volunteers.
      Sympathetic nervous system activation, with reflex dilation of the pupil, was
      produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane,
      and by a rapid 4%-to-8% step-up in the desflurane concentration. Pupil diameter
      and the change in pupil size induced by a light stimulus (light reflex amplitude)
      were measured with infrared pupillometry. RESULTS: Dapiprazole drops produced a
      Horner's miosis, but pupils were equally small after induction of anesthesia.
      Pupillary dilation after noxious stimulation and desflurane step-up was identical
      in the unblocked and dapiprazole-blocked pupils. After tropicamide
      administration, the pupil was dilated and the light reflex was completely
      inhibited. Noxious stimulation nonetheless produced a slight additional dilation.
      CONCLUSIONS: During desflurane anesthesia, pupillary dilation in response to
      noxious stimulation or desflurane step-up is not mediated by the sympathetic
      nervous system (as it is in unanesthetized persons). Although inhibition of the
      pupillo-constrictor nucleus may be the cause of this dilation, the mechanism
      remains unknown.

PMID- 8873545
TI  - Effects of sevoflurane with and without nitrous oxide on human cerebral
      circulation. Transcranial Doppler study.
AB  - BACKGROUND: This study was designed to evaluate the effects of sevoflurane with
      and without nitrous oxide on human middle cerebral artery (MCA) flow velocity,
      cerebrovascular carbon dioxide reactivity, and autoregulation compared with the
      awake state using transcranial Doppler ultrasonography. METHODS: In 14 patients,
      the time-mean middle cerebral artery flow velocity (Vmca) was measured when the
      end-tidal carbon dioxide level was approximately 30, 40, and 50 mmHg under the
      following conditions: (1) awake; (2) with 2% (1.2 MAC) sevoflurane; and (3) with
      1.2 MAC sevoflurane-60% nitrous oxide. In six other patients, the cerebrovascular
      autoregulation during anesthesia was determined using intravenous phenylephrine
      to increase blood pressure. RESULTS: Sevoflurane (1.2 MAC) significantly
      decreased Vmca compared with the awake value at each level of end-tidal carbon
      dioxide, whereas 1.2 MAC sevoflurane-60% nitrous oxide did not exert significant
      influence. The Vmca in normocapnic patients decreased from 69 cm/s to 55 cm/s
      with 1.2 MAC sevoflurane and then increased to 70 cm/s when nitrous oxide was
      added. Sevoflurane (1.2 MAC) with and without 60% nitrous oxide had a negligible
      effect on cerebrovascular carbon dioxide reactivity. A phenylephrine-induced
      increase of mean arterial pressure did not influence Vmca during anesthesia.
      CONCLUSIONS: Sevoflurane (1.2 MAC) reduced Vmca compared with the awake
      condition, whereas the addition of nitrous oxide caused Vmca to increase toward
      the values obtained in the awake condition. The cerebrovascular carbon dioxide
      reactivity and autoregulation were well maintained during 1.2 MAC sevoflurane
      with and without 60% nitrous oxide.

PMID- 8873546
TI  - Human chest wall function during epidural anesthesia.
AB  - BACKGROUND: Although epidural anesthesia (EA) can significantly disrupt the
      function of the respiratory system, data concerning its effects on respiratory
      muscle activity and the resulting motion of the chest wall are scarce. This study
      aimed to determine the effects of lumbar EA on human chest wall function during
      quiet breathing. METHODS: Six persons were studied while awake and during mid
      thoracic (approximately a T6 sensory level) and high (approximately a T1 sensory
      level) lumbar EA produced by either 2% lidocaine (two persons) or 1.5% etidocaine
      (four persons) with 1:200,000 epinephrine. Respiratory muscle activity was
      measured using fine-wire electromyography electrodes. Chest wall configuration
      during high EA was determined using images of the thorax obtained by three
      dimensional, fast computed tomography. The functional residual capacity was
      measured using a nitrogen dilution technique. RESULTS: High EA abolished activity
      in the parasternal intercostal muscles of every participant but one, whereas the
      mean phasic activity of the scalene muscles was unchanged. High EA significantly
      decreased the inspiratory volume displacement of the rib cage compared with
      intact breathing but did not have a significant effect on diaphragm displacement.
      Therefore, high EA decreased the percentage contribution of rib cage expansion to
      inspiratory increases in thoracic volume (delta Vth) (from 27 +/- 2 [MSE] to 10
      +/- 11% of delta Vth). Paradoxic rib cage motion during inspiration (i.e., a net
      inward motion during inspiration) developed in only one participant. High EA
      substantially increased the functional residual capacity (by 295 +/- 89 ml), with
      a significant net caudad motion of the end expiratory position of the diaphragm.
      In addition, high EA significantly decreased the volume of liquid in the thorax
      at end expiration in five of the six participants, a factor that also contributed
      to the increase in functional residual capacity in these persons. CONCLUSIONS:
      Rib cage expansion continues to contribute to tidal volume during high EA in most
      subjects, even when most of the muscles of the rib cage are paralyzed; the mean
      phasic electrical activity of unblocked respiratory muscles such as scalenes does
      not increase in response to rib cage muscle paralysis produced by EA; and high EA
      increases the functional residual capacity, an increase produced in most
      participants by a caudad motion of the diaphragm and a decrease in intrathoracic
      blood volume.

PMID- 8873547
TI  - Effects of motion on the performance of pulse oximeters in volunteers.
AB  - BACKGROUND: Pulse oximetry is considered a standard of care in both the operating
      room and the postanesthetic care unit, and it is widely used in all critical care
      settings. Pulse oximeters may fail to provide valid pulse oximetry data in
      various situations that produce low signal-to-noise ratio. Motion artifact is a
      common cause of oximeter failure and loss of accuracy. This study compares the
      accuracy and data dropout rates of three current pulse oximeters during
      standardized motion in healthy volunteers. METHODS: Ten healthy volunteers were
      monitored by three different pulse oximeters: Nellcor N-200, Nellcor N-3000, and
      Masimo SET (prototype). Sensors were placed on digits 2, 3, and 4 of the test
      hand, which was strapped to a mechanical motion table. The opposite hand was used
      as a stationary control and was monitored with the same pulse oximeters and an
      arterial cannula. Arterial oxygen saturation rate varied from 100% to 75% by
      changing the inspired oxygen concentration. While pulse oximetry was both
      constant and changing, the oximeter sensors were connected before and during
      motion. Oximeter errors and dropout rates were digitally recorded continuously
      during each experiment. RESULTS: If the oximeter was functioning before motion
      began, the following are the percentages of time when the instrument displayed a
      pulse oximetry value within 7% of control: N-200 = 76%, N-3000 = 87%, and Masimo
      = 99%. When the oximeter sensor was connected after the beginning of motion, the
      values were N-200 = 68%, N-3000 = 47%, and Masimo = 97%. If the alarm threshold
      was chosen as pulse oximetry less than 90%, then the positive predictive values
      (true alarms/ total alarms) are N-200 = 73%, N-3000 = 81%, and Masimo = 100%. In
      general, N-200 had the greatest pulse oximetry errors and N-3000 had the highest
      dropout rates. CONCLUSIONS: The mechanical motions used in this study
      significantly affected oximeter function, particularly when the sensors were
      connected during motion, which requires signal acquisition during motion. The
      error and dropout rate performance of the Masimo was superior to that of the
      other two instruments during all test conditions. Masimo uses a new paradigm for
      oximeter signal processing, which appears to represent a significant advance in
      low signal-to-noise performance.

PMID- 8873548
TI  - Minimum alveolar concentration of halothane and enflurane are decreased in early
      pregnancy.
AB  - BACKGROUND: Minimum alveolar concentration (MAC) of isoflurane is decreased in
      early pregnancy but it is not known whether this occurs to the same extent with
      other inhalational anesthetics. The MAC of halothane and enflurane were compared
      in pregnant women undergoing elective termination of pregnancy and in nonpregnant
      women. METHODS: We studied 16 pregnant women scheduled for termination of
      pregnancy at 8 to 13 weeks gestation and 16 non-pregnant patients undergoing
      laparoscopic sterilization. Eight patients in each group received halothane and
      the others received enflurane. After inhalational induction of anesthesia and
      tracheal intubation, MAC was determined in each patient by observing the motor
      response to a 10-s, 50-Hz, 80-mA transcutaneous electric tetanic stimulus to the
      ulnar nerve at varying concentrations of either halothane or enflurane. The end
      tidal concentration of inhalational anesthetic was kept constant for at least 15
      min before each stimulus and the concentration was varied ultimately in steps of
      0.05 vol% (halothane) or 0.10 vol% (enflurane) until a sequence of three
      alternate responses (move, not move, move) or (not move, move, not move) was
      obtained. Minimum alveolar concentration for each person was taken as the mean of
      the two concentrations just permitting and just preventing movement, and MAC for
      the group was the median of individual MAC values. Confidence intervals were
      calculated for the percentage decrease in MAC for pregnant women compared with
      nonpregnant women. RESULTS: The median (range) MAC of halothane, 0.58 vol% (0.53
      to 0.58), and enflurane, 1.15 vol% (0.95-1.25), in the pregnant women were less
      than those in the nonpregnant women, 0.75 vol% (0.70 to 0.78), P = 0.0005 and
      1.65 vol% (1.45 to 1.75), P = 0.0007, respectively. The percentage decrease (95%
      CI) in MAC for pregnant women was 27% (20 to 27%) for halothane and 30% (24 to
      36%) for enflurane. CONCLUSIONS: The MAC of halothane and enflurane were reduced
      by a similar degree in pregnant women at 8 to 13 weeks gestation compared with
      nonpregnant women.

PMID- 8873549
TI  - Effects of general anesthesia and paralysis on upper airway changes due to head
      position in humans.
AB  - BACKGROUND: In supine patients with their heads in flexion, general anesthesia
      causes posterior displacement of upper airway structures that is associated with
      airway obstruction, and extension of the head helps restore patency. However, the
      independent effects of head position, general anesthesia, and muscle paralysis on
      upper airway structures are not known. METHODS: Lateral radiographs of the neck
      were taken in supine patients with the head in flexion and extension, during
      consciousness, and after induction of general anesthesia and muscle paralysis.
      The following measurements were made distances from the horizontal plane to the
      epiglottis, the hyold, and the thyroid cartilage to detect anteroposterior
      displacements; distances from the transverse plane to the hyold and the thyroid
      cartilage to detect cephalocaudad displacements; and widths of the oropharynx,
      the laryngeal vestibule, and the laryngeal sinus. RESULTS: With the head in
      flexion, anesthesia and paralysis compared with the conscious state caused
      posterior displacement of the epiglottis, narrowing of the oropharynx, and
      widening of the laryngeal vestibule. With the head in extension, anesthesia and
      paralysis compared with the conscious state caused anterior displacements of the
      epiglottis, the hyold, and the thyroid cartilage, narrowing of the oropharynx,
      and widening of the laryngeal vestibule and the laryngeal sinus. CONCLUSION: Loss
      of tonic muscular activity due to anesthesia and paralysis results in
      anteroposterior displacements of the upper airway structures with flexion and
      extension of the head that are in the same direction as that of the mandible.
      Anesthesia and paralysis also widen the dimensions of the larynx. These changes
      might have implications for instrumentation and protection of the airway during
      general anesthesia or unconsciousness.

PMID- 8873550
TI  - Mechanism of myocardial protection by isoflurane. Role of adenosine triphosphate
      regulated potassium (KATP) channels.
AB  - BACKGROUND: The mechanism of the protective actions of volatile anesthetics in
      ischemic myocardium has not been clearly elucidated. The role of myocardial
      adenosine triphosphate-regulated potassium (KATP) channels in isoflurane-induced
      enhancement of recovery of regional contractile function after multiple brief
      occlusions and reperfusion of the left anterior descending coronary artery (LAD)
      was studied in dogs anesthetized with barbiturates. METHODS: Dogs (n = 32) were
      instrumented to measure left ventricular and aortic blood pressure, cardiac
      output, LAD coronary blood flow velocity, and subendocardial segment length.
      Regional myocardial perfusion was measured using radioactive microspheres.
      Hemodynamics and percentage segment shortening (%SS) in the LAD perfusion
      territory were evaluated after instrumentation was complete; after pretreatment
      with the KATP channel antagonist, glyburide (0.05 mg/kg-1) or drug vehicle
      (polyethylene glycol in ethyl alcohol; control experiments); and in the presence
      or absence of 1 MAC isoflurane administered for 30 min before and during five 5
      min occlusions and reperfusion of the LAD in four experimental groups. Isoflurane
      was discontinued at the onset of the final reperfusion period. Measurements of
      hemodynamics, %SS, and myocardial perfusion were repeated at several intervals
      during 180 min after reperfusion of the LAD. RESULTS: Left anterior descending
      coronary artery occlusion caused regional dyskinesia during each 5-min occlusion
      in each dog. Control and glyburide-pretreated dogs demonstrated poor recovery of
      %SS by 180 min after reperfusion (2 +/- 10 and 7 +/- 6% of baseline,
      respectively). In contrast, dogs anesthetized with isoflurane exhibited complete
      recovery of function (%SS) by 180 min after reperfusion (82 +/- 8% of baseline).
      Enhanced recovery of regional contractile function by isoflurane was abolished by
      pretreatment with glyburide 180 min after reperfusion (16 +/- 10% of baseline).
      Improvement of functional recovery of stunned myocardium by isoflurane, and the
      blockade of this action by glyburide, was not associated with changes in
      hemodynamics or regional myocardial perfusion. CONCLUSIONS: The results indicate
      that isoflurane prevents decreased systolic shortening caused by multiple
      episodes of ischemia and reperfusion. These actions result in improved recovery
      of contractile function of postischemic, reperfused myocardium and are mediated
      by isoflurane-induced activation of KATP channels.

PMID- 8873551
TI  - Peripheral and spinal actions of opioids in the blockade of the autonomic
      response evoked by compression of the inflamed knee joint.
AB  - BACKGROUND: Three types of opioid receptors, mu, delta, and kappa, are present in
      the periphery and in the central nervous system. In contrast to the effects in
      the central nervous system, the antinociceptive action of opioids in the
      periphery is not as well characterized. The effects of intraarticular, spinal,
      and intramuscular injections of mu, delta, and kappa opioid agonists on the
      autonomic response evoked by compression of an inflamed knee joint were
      evaluated. METHODS: In halothane-anesthetized rats, arthritis was induced by
      injecting kaolin and carrageenan into the right knee joint. Standardized
      compression of the knee joint by inflation of a pediatric blood pressure cuff to
      200 mmHg for 2 min produced a reliable stimulus-dependent hypertension (delta =
      13 mmHg). Drugs were delivered intramuscularly, intrathecally through a chronic
      catheter, or intraarticularly into the right knee joint. The drug injection was
      performed 4 hr after induction of the inflammation. RESULTS: The intrathecal
      administration of mu, delta, and kappa agonists resulted in a dose-dependent
      blockade of the cuff-evoked increase in blood pressure. The order of intrathecal
      drug activity on the compression-evoked blood pressure responses with median
      effective dose (ED50) was sufentanil (0.02 nmol; mu) > PD117302 (0.5 nmol;
      kappa); spiradoline (1.5 nmol; kappa) morphine (2.4 nmol; mu) > DADL (15 nmol;
      delta); DPDPE (18 nmol; delta) > U-50,488H (620 nmol; kappa) > naloxone = 0. The
      intraarticular administration of mu and kappa, but not delta agonists, produced a
      dose-dependent blockade of a compression-evoked increase in blood pressure, with
      the order of drug activity (ED40) as follows: sufentanil (0.04 mumol) > PD117302
      (0.3 mumol); spiradoline (0.8 mumol), morphine (0.9 mumol) > U-50,488H (0.9
      mumol) > DPDPE (> 5 mumol); DADL (> 18 mumol) > naloxone = 0. Intramuscular
      injection of these agonists caused suppression, with the order of drug activity
      (ED50) as follows: sufentanil (0.2 mumol) > PD117302 (2 mumol); spiradoline (11
      mumol) morphine (9 mumol) > DPDPE (> 5 mumol); DADL (18 mumol) > U-50,488H (22
      mumol) > naloxone = 0. All intraarticular effects were reversible by injecting
      naloxone intramuscularly, with the ordering of naloxone potency against
      equiactive doses of morphine > U50,488H. CONCLUSIONS: The activity of the
      respective agonists and the intraarticular > intramuscular ordering of systemic
      potency in this model indicate that opioids, by an action at mu and kappa, can
      exert a direct antihyperalgesic action at the terminals of primary afferents
      projecting to a region of inflammation. These observations offer strong support
      for a peripheral action of opioids in certain states in inflammation-induced
      hyperalgesia.

PMID- 8873552
TI  - Effect of acute respiratory acidosis on the limits of oxygen extraction during
      hemorrhage.
AB  - BACKGROUND: Hypercapnia can impair cells' capacity to maintain energy status
      anerobically and enhances the risk of hypoxic injury when oxygen availability is
      reduced. The ability to maintain tissue oxygenation is determined by both bulk
      blood flow and the efficiency of oxygen extraction. Bulk blood flow is maintained
      during hypercapnia through increased sympathetic activity. The effect of
      hypercapnia on oxygen extraction, however, is unknown. This study evaluates the
      effect of hypercapnia on cells' capacity to adapt to reductions in oxygen
      availability by increasing oxygen extraction. METHODS: In three groups of
      paralyzed, mechanically ventilated dogs that were anesthetized with alpha
      chloralose, the concentration of carbon dioxide in the inhaled gas mixture was
      adjusted to achieve normocapnia, moderate hypercapnia (Paco2 = 72 +/- 3 [SE]
      mmHg) or severe hypercapnia (Paco2 = 118 +/- 4 [SE] mmHg). Stepwise hemorrhage
      was induced until each dog's blood pressure was destabilized. At each stage in
      the hemorrhage protocol, the oxygen delivery, oxygen consumption, and oxygen
      extraction ratios (ratio of arteriovenous oxygen content difference to arterial
      oxygen content) were determined. RESULTS: At the point of onset of delivery
      dependence of oxygen consumption, the oxygen delivery rate (critical oxygen
      delivery) was 7.8 +/- 1.5 (SE) ml.kg-1.min-1 and the oxygen extraction ratio
      (critical oxygen extraction ratio) was 0.72 +/- 0.04 (SE) in the normocapnic
      dogs. Moderate hypercapnia had no effect on these parameters. In the severely
      hypercapnic dogs, the critical values for oxygen delivery and extraction ratios
      were 12.5 +/- 1.8 (SE) ml.kg-1.min-1 and 0.54 +/- 0.035 (SE), respectively (P <
      0.05 for differences from the normocapnic dogs). CONCLUSIONS: The results
      identify a previously unrecognized threat to tissue oxygenation and emphasize the
      importance of ensuring adequate oxygen delivery when adopting mechanical
      ventilatory strategies that permit respiratory acidosis to develop.

PMID- 8873553
TI  - Volatile anesthetics depress glutamate transmission via presynaptic actions.
AB  - BACKGROUND: Recent evidence for a presynaptic depression of glutamate release
      produced by volatile anesthetics prompted the current study of isoflurane and
      halothane effects on glutamate-mediated transmission in the mammalian central
      nervous system. METHODS: Electrophysiologic recordings from CA1 neurons in rat
      hippocampal brain slices were used to measure anesthetic effects on glutamate
      mediated excitatory postsynaptic potential (EPSP) amplitudes and paired pulse
      facilitation. Paired pulse facilitation is known to be altered when the calcium
      dependent release of glutamate is depressed, but not when EPSP amplitudes are
      depressed by postsynaptic mechanisms. RESULTS: Isoflurane depressed EPSP
      amplitudes over a concentration range of 0.35-2.8 vol %, with a 50% depression
      (EC50) occurring at 1.0 vol % (0.71 rat minimum alveolar concentration). This
      depression was accompanied by an increase in paired-pulse facilitation of
      approximately 30% at 1.7 vol %, using interpulse intervals of 120 ms. Halothane
      depressed EPSP amplitudes in a concentration-dependent manner (0.3-2.4 vol %,
      EC50 = 1.1 minimum alveolar concentration; 1.3 vol %) and also increased
      facilitation by approximately 20% at 1.2 vol %. These effects persisted in the
      presence of 10 microM bicuculline, indicating that enhanced gamma-aminobutyric
      acid-mediated inhibition was not involved. The anesthetic-induced increase in
      facilitation and EPSP depression was mimicked by lowering extracellular calcium,
      which is known to depress glutamate release at these synapses. The postsynaptic
      glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione depressed EPSP
      amplitudes with no change in facilitation. CONCLUSIONS: Our results confirm
      earlier findings that clinically relevant concentrations of volatile anesthetics
      depress glutamate-mediated synaptic transmission. The observed increases in
      synaptic facilitation support recent findings from biochemical and
      electrophysiologic studies indicating presynaptic sites of action contribute to
      anesthetic-induced depression of excitatory transmission. This anesthetic-induced
      reduction in glutamate release would contribute to the central nervous system
      depression associated with anesthesia by adding to postsynaptic depressant
      actions on glutamate receptors.

PMID- 8873554
TI  - Clonidine, but not morphine, delays the development of thermal hyperesthesia
      induced by sciatic nerve constriction injury in the rat.
AB  - BACKGROUND: It has been shown that the spinal facilitation induced by the injury
      discharge evoked by a nerve constriction injury is crucial in the development of
      thermal hyperesthesia. Both opioids and alpha 2 agonists have been reported to
      prevent the development of spinal facilitation evoked by the small afferent input
      to the spinal cord. Moreover, it has been reported that the thermal hyperesthesia
      induced by a nerve constriction injury is sympathetically maintained and that
      spinally administered alpha 2 agonists can modulate the sympathetic outflow from
      the spinal cord. The current study investigated the effect of spinally
      administered morphine and clonidine, an alpha 2 agonist, on the development of
      thermal hyperesthesia induced by nerve constriction injury in the rat. METHODS: A
      model of thermal hyperesthesia induced by a constriction injury created by making
      four loose ligatures around the rat sciatic nerve was used to examine the
      development of thermal hyperesthesia. Morphine, clonidine, and idazoxan were
      administered intrathecally or intraperitoneally 20 min before (pretreatment
      study) or 20 min after (posttreatment study) the nerve injury. RESULTS:
      Pretreatment, but not posttreatment, with intrathecal clonidine significantly
      delayed the development of thermal hyperesthesia in a dose-dependent manner, and
      this delay in onset produced by clonidine was 3 days after the nerve injury. This
      effect of clonidine's was completely antagonized by the coadministration of
      idazoxan with clonidine. Intrathecal morphine had no effect on the development of
      thermal hyperesthesia in this study. CONCLUSIONS: Spinal alpha 2 receptors, but
      not opioid receptors, may play an important role in the development of thermal
      hyperesthesia induced by a nerve constriction injury. This suggested that the
      activation of spinal alpha 2 receptor may reduce the sympathetic outflow and this
      reduction of sympathetic outflow may be the key mechanism that delays the
      development of thermal hyperesthesia.

PMID- 8873555
TI  - Antinociceptive response to nitrous oxide is mediated by supraspinal opiate and
      spinal alpha 2 adrenergic receptors in the rat.
AB  - BACKGROUND: Despite nearly 150 years of clinical use, the mechanism(s) of action
      of nitrous oxide (N2O) remains in doubt. In some but not all studies the
      analgesic properties of N2O can be attenuated by opiate receptor antagonists. The
      purported mechanism for the opiate antagonistic effect relates to the finding
      that N2O increases supraspinal levels of endogenous opiates, although this
      finding has been disputed. Based on the observations that (1) N2O promotes the
      release of catecholamines, including the endogenous alpha 2 adrenergic agonist
      norepinephrine, and (2) that descending noradrenergic inhibitory pathways are
      activated by opioid analgesics, this study sought to determine whether alpha 2
      adrenergic receptors are involved in the antinociceptive action of nitrous oxide.
      METHODS: Institutional approval was obtained for the study. Rats breathed 70% N2O
      and 30% O2 in an enclosed chamber. After a 30-min exposure, significant
      antinociception was indicated by an increase in the latency response to a noxious
      stimulus (tail-flick latency). The tail-flick latency was tested in rats exposed
      to 70% N2O after either systemic or regional (intrathecal or
      intracerebroventricular) injections with either competitive (atipamezole;
      yohimbine) or noncompetitive (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline)
      alpha 2 adrenoceptor antagonists, or the opiate receptor antagonist naloxone.
      RESULTS: When administered systemically, both the opiate (naloxone) and alpha 2
      adrenoceptor antagonists (atipamezole, yohimbine, and N-ethoxycarbonyl-2-ethoxy
      1,2-dihydroquinoline) blocked the enhanced tail-flick latency response to N2O
      Naloxone administered intracerebroventricularly, but not intrathecally, blocked
      the enhanced tail-flick latency response to N2O. Conversely, atipamezole
      administered intrathecally, but not intracerebroventricularly, blocked the
      enhanced tail-flick latency response to N2O. CONCLUSIONS: These data suggest that
      both supraspinal opiate and spinal alpha 2 adrenoceptors play a mediating role in
      the antinociceptive response to N2O in rats. A possible mechanism may involve a
      descending inhibitory noradrenergic pathway that may be activated by opiate
      receptors in the periaqueductal gray region of the brain stem in the rat after
      exposure to N2O.

PMID- 8873556
TI  - Prevention of lidocaine aerosol-induced bronchoconstriction with intravenous
      lidocaine.
AB  - BACKGROUND: Lidocaine applied topically provokes bronchoconstriction in persons
      with hyperreactive airway disease. The authors questioned whether intravenous
      lidocaine would prevent lidocaine-aerosol induced bronchoconstriction. They
      compared the effects of lidocaine administered intravenously and by the aerosol
      route on baseline airway tone, and on the prevention of histamine-induced
      bronchoconstriction in five Basenji-Greyhound dogs. METHODS: Dogs were pretreated
      with either intravenous or aerosol lidocaine followed by histamine aerosol
      challenge. On separate days, dogs were pretreated with intravenous lidocaine,
      followed by aerosol lidocaine administration at similar doses. Airway caliber was
      assessed using high-resolution computed tomography. Data were analyzed by two-way
      analysis of variance. Serum lidocaine concentrations were obtained. RESULTS:
      Histamine alone decreased the airway area by 32 +/- 3%. Lidocaine administered
      intravenously or by the aerosol route significantly inhibited histamine-induced
      bronchoconstriction. There was no significant difference between the two routes
      in preventing histamine-induced bronchoconstriction. At the dose that inhibited
      histamine-induced bronchoconstriction, lidocaine administered by the aerosol
      route decreased baseline airway area by 27 +/- 3% (P < 0.01), whereas intravenous
      lidocaine had no effect. Intravenous lidocaine prevented lidocaine aerosol
      induced bronchoconstriction, and the combination of intravenous and aerosol
      lidocaine significantly dilated the airways by 20 +/- 5% (P < 0.01 compared with
      control). CONCLUSIONS: An intravenous bolus of lidocaine prevents the initial
      bronchoconstriction induced by lidocaine when administered as an aerosol.

PMID- 8873557
TI  - Inhibition of endogenous nitric oxide synthase potentiates nitrovasodilators in
      experimental pulmonary hypertension.
AB  - BACKGROUND: The role of endogenous nitric oxide (NO) in the regulation of
      pulmonary vascular tone is complex. Inhibition of endogenous NO synthase,
      potentially through upregulation of guanylyl cyclase, results in an increase in
      potency of nitrovasodilators in the systemic circulation. This study considered
      whether inhibition of endogenous NO synthase would increase the potency of
      nitrovasodilators, but not of cyclic adenosine monophosphate-dependent
      vasodilators, in the pulmonary vasculature. METHODS: We used the isolated buffer
      perfused rabbit lung. Preparations were randomized to receive either pretreatment
      with NG-nitro-L-arginine methyl ester (or L-NAME, an inhibitor of endogenous NO
      synthase) or no pretreatment. Stable pulmonary hypertension was then produced by
      infusing the thromboxane A2 analog U46619. The dose-response characteristics of
      two nitrovasodilators, sodium nitroprusside and nitroglycerin, and two
      nonnitrovasodilators, prostaglandin E2 and 5'-N-ethylcarboxamidoadenosine, were
      studied. RESULTS: Inhibition of endogenous NO synthase caused no significant
      changes in baseline pulmonary artery pressure but did significantly reduce the
      U46619 infusion rate required to produce pulmonary hypertension. Pretreatment
      with L-NAME (vs. no L-NAME) resulted in significantly lower values of the log
      median effective dose with sodium nitroprusside and nitroglycerin. In contrast,
      pretreatment with L-NAME resulted in no changes in the dose-response
      characteristics of the cyclic adenosine monophosphate-mediated, NO-independent
      vasodilators prostaglandin E1 and 5'-N-ethylcarboxamidoadenosine. CONCLUSIONS:
      These data suggest that endogenous NO synthase is not an important regulator of
      basal pulmonary tone in this model but is an important modulator of pulmonary
      vascular responses to vasoconstriction and to nitrovasodilators. The pulmonary
      vasodilator effects of nitrovasodilators, but not of nonnitrovasodilators, may
      depend on the level of activity of NO synthase.

PMID- 8873558
TI  - Ipratropium decreases airway size in dogs by preferential M2 muscarinic receptor
      blockade in vivo.
AB  - BACKGROUND: Two major groups of drugs are available to prevent
      bronchoconstriction: beta-agonists and muscarinic blocking agents. Ipratropium is
      the most commonly used anticholinergic agent to treat chronic obstructive
      pulmonary disease. The authors studied anti-muscarinic agents to determine if
      they are as effective bronchodilators as beta-adrenergic agents and if not to
      identify the mechanism of their reduced effectiveness. METHODS: Six anesthetized
      dogs were studied using high-resolution computed tomography to measure changes in
      the cross-sectional area of conducting airways induced by cumulative doses of
      ipratropium with and without gallamine, a selective M2 muscarinic receptor
      blocker, and after metaproterenol. RESULTS: Metaproterenol dilated the airways
      and ipratropium constricted the airways. Ipratropium in concentrations of 0.01
      and 0.1 mg/ml constricted the airways to 22 +/- 2% and 20 +/- 3% of control,
      respectively (P < 0.01), whereas larger concentrations caused bronchodilation.
      After complete blockade of the M2 receptors by pretreatment with intravenous
      gallamine, the bronchoconstrictor effect of ipratropium was abolished, and
      ipratropium dilated the airways by 16 +/- 8% and 27 +/- 10% of pre-gallamine
      baseline after doses of 0.01 and 0.1 mg/ml, respectively (P < 0.01). CONCLUSION:
      Low-dose ipratropium can decrease airway size by the initial, preferential
      blockade of neuronal M2 muscarinic receptors, whereas a larger dose of
      ipratropium blocks M3 muscarinic receptors on airway smooth muscle, resulting in
      bronchodilation.

PMID- 8873559
TI  - Halothane and diazepam inhibit ketamine-induced c-fos expression in the rat
      cingulate cortex.
AB  - BACKGROUND: Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has
      psychotomimetic side effects. Recent studies have shown that noncompetitive N
      methyl-D-aspartate antagonists cause morphologic damage to the cingulate and
      retrosplenial cortices and induce c-fos protein (c-Fos) in the same regions.
      Although benzodiazepines are effective in preventing these side effects, the
      neural basis of the drug interactions has not been established. METHODS: The
      effects of diazepam and halothane on c-Fos expression induced by ketamine were
      studied. Diazepam (1 and 5 mg/kg) or vehicle were administered subcutaneously,
      followed 7 min later by 100 mg/kg ketamine given intraperitoneally. Halothane
      (1.0 and 1.8%), was administered continuously from 10 min before ketamine
      administration until brain fixation. Two hours after ketamine injection, rats
      were perfused and their brains fixed and extracted. Brain sections were prepared
      in a cryostat and c-Fos expression was detected using immunohistochemical
      methods. RESULTS: Ketamine induced c-Fos-like immunoreactivity in the cingulate
      and retrosplenial cortices, thalamus, and neocortex. Diazepam suppressed the
      ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial
      cortices in a dose-dependent manner, leaving the thalamus and neocortex less
      affected. Halothane suppressed the ketamine-induced c-Fos-like immunoreactivity
      in the cingulate and retrosplenial cortices and the neocortex in a dose-dependent
      manner, leaving the thalamus relatively unaffected. CONCLUSION: Halothane and
      diazepam inhibited ketamine-induced c-Fos expression in the cingulate and
      retrosplenial cortices, leaving the thalamus relatively unaffected.

PMID- 8873560
TI  - Epidural catheter reconnection. Safe and unsafe practice.
AB  - BACKGROUND: An in vitro model of epidural catheter contamination was used to
      determine if disconnected catheters can be safely reconnected. METHODS: Epidural
      catheters were filled with brain-heart infusion (BHI) broth or preservative-free
      saline containing 5 micrograms/ml fentanyl. Escherichia coli, Pseudomonas
      aeruginosa, or Staphylococcus aureus (1.10(5) colony-forming units) was injected
      into the initial 1.1 +/- 0.24 inch (2.75 +/- 0.60 cm) of the catheters. To study
      the effect of bacteria settling in a vertically oriented catheter on the
      advancement of bacteria along the catheter, bacteria were incubated with
      catheters in the vertical and the horizontal positions. To determine if bacteria
      are swept further into a catheter when fluid in it is displaced, catheters were
      inclined 30 degrees and the fluid in them was allowed to drain from the distal
      end to various extents. Bacteria were incubated with the catheter held
      horizontally. After incubation, the catheters were serially sectioned, and the
      resulting segments were eluted with buffered saline-containing gelatin (BSG),
      which was collected on BHI agar plates for colony counts. This determined if a
      segment of the catheter remained internally sterile distal to the point of
      disconnection. Effectiveness of decontaminating the exterior of the catheter was
      also tested as follows: Catheters (n = 10) were first immersed in BSG containing
      1.10(5) S, aureus, immediately immersed in betadine for 2 min, exposed to air for
      3 min, cut with a sterile instrument, and reconnected to a sterile screw cap
      catheter connector. Reconnected catheters were perfused with 10 ml BSG for 1 hr.
      Collected perfusate (100 microliters) was removed for direct colony count; the
      remaining perfusate was mixed with an equal volume of BHI and incubated
      overnight. A 100 microliters aliquot of BHI-BSG mixture was sampled the next day.
      No bacteria were cultured from either the perfusate or BHI-BSG mixture. RESULTS:
      Eight hours after contamination, as long as the fluid in the catheter was static,
      no bacteria were detected more than 13 inches (32.5 cm) from the contaminated end
      of catheters filled with BHI and no more than 8 inches (20 cm) from the end of
      those filled with fentanyl solution. This finding was not affected by incubation
      of the catheter in the vertical position. Fluid displacement less than 8 inches
      (20 cm) had no effect on dissemination, but when fluid was displaced 13 inches
      (32.5 cm), bacteria were found at the end of the catheter, 35 inches (87.5 cm)
      away. No bacteria were recovered from the perfusate of reconnected catheters
      after the catheters were cleaned with betadine and cut with a sterile instrument.
      CONCLUSIONS: There may be an area distal to the disconnected end of an epidural
      catheter where its interior remains sterile for at least 8 hr. Such an area
      exists only when the fluid in the catheter remains static. Furthermore, the
      exterior of the catheter can be adequately cleaned to prevent bacteria from
      entering the catheter when reconnected at that point.

PMID- 8873561
TI  - Volatile general anesthetics produce hyperpolarization of Aplysia neurons by
      activation of a discrete population of baseline potassium channels.
AB  - BACKGROUND: The mechanism by which volatile anesthetics act on neuronal tissue to
      produce reversible depression is unknown. Previous studies have identified a
      potassium current in invertebrate neurons that is activated by volatile
      anesthetics. The molecular components generating this current are characterized
      here in greater detail. METHODS: The cellular and biophysical effects of
      halothane and isoflurane on neurons of Aplysia californica were studied. Isolated
      abdominal ganglia were perfused with anesthetic-containing solutions while
      membrane voltage changes were recorded. These effects were also studied at the
      single-channel level by patch clamping cultured neurons from the abdominal and
      pleural ganglia. RESULTS: Clinically relevant concentrations of halothane and
      isoflurane produced a slow hyperpolarization in abdominal ganglion neurons that
      was sufficient to block spontaneous spike firings. Single-channel studies
      revealed specific activation by volatile anesthetics of a previously described
      potassium channel. In pleural sensory neurons, halothane and isoflurane increased
      the open probability of the outwardly rectifying serotonin-sensitive channel (S
      channel). Halothane also inhibited a smaller noninactivating channel with a
      linear slope conductance of approximately 40 pS. S channels were activated by
      halothane with a median effective concentration of approximately 500 microM
      (0.013 atm), which increased channel activity about four times. The mechanism of
      channel activation involved shortening the closed-time durations between bursts
      and apparent recruitment of previously silent channels. CONCLUSIONS: The results
      demonstrate a unique ability of halothane and isoflurane to activate a specific
      class of potassium channels. Because potassium channels are important regulators
      of neuronal excitability within the mammalian central nervous system, background
      channels such as the S channel may be responsible in part for mediating the
      action of volatile anesthetics.

PMID- 8873562
TI  - Behavioral effects of volatile anesthetics in Caenorhabditis elegans.
AB  - BACKGROUND: The nematode Caenorhabditis elegans offers many advantages as a model
      organism for studying volatile anesthetic actions. It has a simple, well
      understood nervous system; it allows the researcher to do forward genetics; and
      its genome will soon be completely sequenced. C. elegans is immobilized by
      volatile anesthetics only at high concentrations and with an unusually slow time
      course. Here other behavioral dysfunctions are considered as anesthetic endpoints
      in C. elegans. METHODS: The potency of halothane for disrupting eight different
      behaviors was determined by logistic regression of concentration and response
      data. Other volatile anesthetics were also tested for some behaviors. Established
      protocols were used for behavioral endpoints that, except for pharyngeal pumping,
      were set as complete disruption of the behavior. Time courses were measured for
      rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined
      for mating, chemotaxis, and gross movement. All experiments were performed at 20
      to 22 degrees C. RESULTS: The median effective concentration values for halothane
      inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and
      coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum
      alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility
      with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had
      intermediate sensitivities. Halothane's effects reached steady-state in 10 min
      for all behaviors tested except immobility, which required 2 h. Recovery was
      complete after exposure to 1 vol% halothane but was significantly reduced after
      exposure to immobilizing concentrations. CONCLUSIONS: Volatile anesthetics
      selectively disrupt C. elegans behavior. The potency, time course, and recovery
      characteristics of halothane's effects on three behaviors are similar to its
      anesthetic properties in vertebrates. The affected nervous system molecules may
      express structural motifs similar to those on vertebrate anesthetic targets.

PMID- 8873563
TI  - Tait and Caglieri. The first spinal anesthetic in America.

PMID- 8873564
TI  - Lumbar and thoracic epidural blood injections to treat spontaneous intracranial
      hypotension.

PMID- 8873565
TI  - Spontaneous intracranial hypotension: a series.

PMID- 8873566
TI  - Demonstration of false lumen perfusion during repair of type A aortic dissection.

PMID- 8873567
TI  - Hemodynamic response to anesthesia and pneumoperitoneum in orthotopic cardiac
      transplant recipients.

PMID- 8873568
TI  - Remote cocaine use as a likely cause of cardiogenic shock after penetrating
      trauma.

PMID- 8873569
TI  - Ventricular dysrhythmia in the native heart after heterotopic heart
      transplantation: diagnosis with selective electrocardiography.

PMID- 8873570
TI  - Alveolar air equations.

PMID- 8873571
TI  - Cerebral oxygenation during deep hypothermic cardiopulmonary bypass: is
      hemoglobin relevant?

PMID- 8873572
TI  - Oral obturator a useful adjunct for fiberoptic tracheal intubation.

PMID- 8873573
TI  - Blood pressure measurements and intravenous infusions: a simple clamp to prevent
      retrograde blood flow.

PMID- 8873574
TI  - Dural puncture as a complication of internal jugular vein cannulation.

PMID- 8873575
TI  - Resident accountability.

PMID- 8873576
TI  - Anesthesia for transjugular intrahepatic portosystemic shunt placement.

PMID- 8873577
TI  - Early impressions of the harmonic scalpel.

PMID- 8873578
TI  - Changes in cardiac autonomic activities in patients with syndrome X. A study of
      spectral analysis of heart rate variability.
AB  - The present study was designed to assess cardiac autonomic activities, coronary
      microvascular function, and their relationship in patients with syndrome X.
      Control of coronary blood flow is complex, and impaired coronary flow reserve has
      been attributed as the cause of myocardial ischemia in patients with syndrome X.
      It is unknown whether cardiac autonomic activities are altered in the presence of
      coronary microvascular dysfunction in patients with syndrome X. Eighteen patients
      with syndrome X were studied. Great cardiac vein flow was measured by the
      thermodilution method and the coronary flow reserve was determined by intravenous
      dipyridamole (0.56 mg/kg) infusion. Twenty-four-hour ambulatory
      electrocardiograms were obtained in a drug-free state. Another 14 age- and sex
      matched normal subjects served as a control group. The amplitude (in ms) of
      ultralow (ULF), very-low (VLF), low (LF), and high (HF) frequency bands and total
      spectra of heart rate variability were measured for twenty-four-hour and every
      four-hour interval of the day.

PMID- 8873579
TI  - Use of TPA-induced clot lysis time (TCLOT) to diagnose abnormal clot structure
      and fibrinolysis in a patient with spontaneous bleeding into his leg.
AB  - Diagnosis and treatment of patients with bleeding due to enhanced fibrinolysis is
      hampered by the absence of a rapid screen of fibrinolytic potential. The authors
      have developed a simple assay to assess clot structure and fibrinolysis in
      patient samples exposed to tissue plasminogen activator (TPA). They present the
      case of a forty-one-year-old man who presented with spontaneous bleeding despite
      normal results from coagulation screening tests, platelet count, platelet
      aggregation studies, platelet force development, and bleeding time. Evaluation of
      the patient's clot structure revealed a very weak, low-modulus, clot that rapidly
      dissolved in the presence of TPA. Identification of the abnormality allowed
      treatment with epsilon-aminocaproic acid with prompt resolution of bleeding.

PMID- 8873580
TI  - Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin
      clot lysis time in patients with mild hypertension.
AB  - Thirteen patients with mild hypertension (untreated diastolic blood pressure of
      95 to 114 mmHg) received, in random order, three successive treatments of four
      weeks with placebo, spirapril (6 mg daily), or hydrochlorothiazide (HCT2) (24 mg
      daily). At the end of each treatment, blood samples for assessment of platelet
      aggregation and platelet release of platelet factor 4 (PF4) and for assessment of
      fibrinolysis, estimated by tissue plasminogen activator (t-PA), plasminogen
      activator inhibitor-type 1 (PAI-1), and euglobulin clot lysis time (ECLT), were
      taken, first at rest, then immediately after five to ten minutes of vigorous
      exercise, and finally after the subsequent hour of recovery rest. Platelet
      aggregation induced in vitro by adrenaline significantly decreased during
      treatment with HCT2, the threshold rising to 10 microM as compared with 1.0 with
      placebo (P < 0.05) at rest, and the threshold for adenosine diphosphate (ADP)
      aggregation also rose, from 2 microM to 4 (NS). The resting plasma PF4 value
      fell, although not significantly, during HCT2 treatment from the placebo value of
      3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the
      threshold of either adrenaline or ADP for aggregation of platelets sampled at
      rest, and the PF4 plasma levels showed no significant reductions at rest.
      However, during exercise PF4 showed an approximate doubling of the resting value
      irrespective of therapy. This exercise-induced increase in PF4 was significantly
      reduced by spirapril as compared with placebo (P < 0.05). ECLT and t-PA did not
      shift significantly from the placebo level during either therapy. PAI-1 did not
      change during spirapril therapy, but during HCT2 treatment it fell, although not
      significantly, to 9.36 IU/mL from 15.91 with placebo (NS). Spirapril and HCT2 did
      not produce any unwanted side effect on platelet function or fibrinolysis. HCT2
      seems to decrease platelet activity at rest, whereas spirapril seems to some
      extent to decrease platelet activity at exercise.

PMID- 8873581
TI  - Ambulatory-determined 24-hour blood pressure in mild hypertensives and in
      normotensives.
AB  - Noninvasive ambulatory twenty-four-hour blood pressure (BP) monitoring was
      carried out in 30 normotensive subjects (16 women, 14 men), aged twenty-five to
      sixty years (mean thirty-eight) and in 29 mild essential hypertensive patients
      without target organ damage (14 women, 15 men), aged twenty-three to sixty-one
      years (mean thirty-nine). Hypertensive patients were not treated, and they
      discontinued any antihypertensive treatment at least four weeks before the study.
      During the daytime period (6 AM-10 PM) BP was monitored every fifteen minutes,
      and during the night (10 PM-6 AM), every thirty minutes. Obviously, mean twenty
      four-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) were
      higher in hypertensive patients (P < 0.001). There was a persistent correlation
      in the group of mild hypertensives between successive BP hourly mean readings (r
      ranged from 0.61 to 0.93 for SBP and from 0.45 to 0.82 for DBP). In normotensive
      subjects these correlations failed in particular periods: 8 AM-9 AM, r = 0.30 for
      SBP and 0.45 for DBP; 1 PM-3 PM, r = 0.17-0.49 for SBP and 0.28-0.37 for DBP; 9
      PM to midnight, r = 0.21-0.57 for SBP and 0.23-0.38 for DBP.

PMID- 8873582
TI  - Risk factors that predict development of microalbuminuria in treated hypertensive
      men. The Risk Factor Intervention Study Group.
AB  - The aim of this prospective study was to investigate the risk factors for
      development of microalbuminuria in treated hypertensive men with and without
      diabetes mellitus. Two hundred and ninety-seven treated hypertensive men, aged
      fifty to seventy-two years, with at least one of the following: serum cholesterol
      > or = 6.5 mmol/L, smoking, or diabetes mellitus, were included in the study.
      Patients with elevated overnight urinary albumin excretion (> 17 mg/12 hr) were
      excluded. Urinary albumin excretion (UAE), blood pressure, and various well
      established risk factor levels were measured. Two hundred thirteen nondiabetic
      patients and 40 patients with diabetes mellitus completed the three-year follow
      up. Development of microalbuminuria was more prevalent in those with diabetes
      mellitus at baseline compared with the group without diabetes mellitus, 25% and
      10.3%, respectively (P = 0.02). Nondiabetic patients who developed
      microalbuminuria had higher UAE. 10.2 mg +/- 3.7 and 5.7 +/- 3.2, respectively (P
      < 0.0001), and higher systolic blood pressure 160 mm Hg +/- 27 and 152 +/- 17,
      respectively (P = 0.043), at baseline compared with whose who remained
      normoalbuminuric. In the group with diabetes mellitus, a higher UAE, 9.8 +/- 2.7
      and 7.1 +/- 3.6, respectively (P = 0.036), at baseline was observed in whose who
      developed microalbuminuria compared with whose who remained normoalbuminuric. In
      conclusion, concomitant diabetes mellitus significantly increased the risk for
      development of microalbuminuria during the three-year follow-up in treated
      hypertensive men. Patients who progressed to microalbuminuria had higher UAE at
      baseline, but still within the normoalbuminuric range, compared with thosewho
      remained normoalbuminuric. Systolic blood pressure at baseline was higher in
      those who progressed to microalbuminuria, although reaching statistically
      significance only in the larger nondiabetic group.

PMID- 8873583
TI  - Effects of right ventricular pacing on ventriculoatrial conduction and systemic
      venous responses in sick sinus patients.
AB  - This study was designed to assess the ventriculoatrial (VA) conduction and
      systemic venous responses to right ventricular pacing at different pacing rates
      and the feasibility of identifying patients prone to pacemaker syndrome by means
      of a Doppler and two-dimensional echocardiographic technique. Twenty-two sick
      sinus patients who received ventricular-demand permanent pacemakers constituted
      the study group. The proximal inferior vena cava (IVC) diameters were measured by
      two-dimensional echocardiography. Fourteen patients had VA conduction by
      preimplant electrophysiologic study or paced electrocardiogram (Group II), while
      the other 8 patients presented no VA conduction (Group I). Abnormal systolic
      retrograde flow in the hepatic vein following each paced beat could be
      demonstrated in those patients with VA conduction in the basal state. In the 8
      patients without VA conduction, the IVC diameters were significantly increased
      during rapid right ventricular pacing in those with left ventricular dysfunction
      (n = 4) as compared with those with normal left ventricular function (n = 4) (%
      increment at 120 beats per minute.

PMID- 8873584
TI  - Ambulatory blood pressure and echocardiographic left ventricular dimensions in
      elderly hypertensive subjects.
AB  - In a consecutive series of 62 hypertensive elderly subjects, the authors studied
      the relation of blood pressure circadian variations with echocardiographic
      parameters of left ventricular (LV) hypertrophy. All the subjects were submitted
      to an ambulatory blood pressure monitoring (ABPM) and to B- and M-mode
      echocardiography. In the elderly hypertensive group, LV mass index (LVMI) was
      more strongly related to twenty-four-hour, daytime and nighttime systolic
      ambulatory blood pressure (r = 0.52, r = 0.37, r = 0.51) than diastolic
      ambulatory blood pressures were (r = 0.32, r = 0.18, r = 0.33). Casual systolic
      and diastolic blood pressure (CBP) was found more weakly related to LVMI than
      ambulatory blood pressures were (r = 0.35, r = 0.26). Elderly hypertensive
      subjects were divided into two subgroups in relation to the presence (group 1) or
      absence (group 2) of blood pressure nocturnal decline. No differences were found
      between these two subgroups in regard to: casual blood pressure values,
      ambulatory blood pressures in the diurnal period, sex, body surface area, height,
      weight, and age. LVMIs were computed in all three groups and showed the following
      results: 89.32 +/- 19.76 in elderly normotensives, 91.21 +/- 31.32 in group 1,
      and 99.80 +/- 18.21 in group 2. Echocardiographic parameters of LV dimensions and
      LVMIs were different in group 1 and 2. An inverse correlation, statistically
      significant, was observed between LVMIs and the nocturnal blood pressure
      reduction (systolic: r = -0.36, P < 0.05; diastolic: r = -0.29, P < 0.05). These
      results suggest an association between a smaller LV mass and nocturnal blood
      pressure decline in elderly hypertensive patients.

PMID- 8873585
TI  - The quantitation of blood flow/metabolism coupling at rest and after exercise in
      peripheral arterial insufficiency, using PET and 15-0 labeled tracers.
AB  - Regional blood flow and oxygen uptake of the lower limbs were studied in 11
      patients with arterial insufficiency (10 with severe unilateral, 1 with bilateral
      intermittent claudication). Regional muscle blood flow (F), oxygen consumption
      rate (R), and oxygen extraction fraction (E) were evaluated by positron emission
      tomography (PET) and bolus inhalation of C15O2 and 15O2 by the patient. Tomograms
      were recorded at the greatest diameter of legs, at rest and ten minutes after a
      treadmill walk test leading to the development of ischemic pain in the affected
      leg. In 5 patients, F and E were correlated with the results of occlusive venous
      strain gauge plethysmography and with the measurements of blood gases in one
      brachial artery and in the femoral vein of the affected limb. Blood flow values
      measured at rest and after exercise by PET were poorly correlated with the
      plethysmographic findings. This may be because PET does not interfere with flow
      as venous occlusion plethysmography does in low peripheral pressure conditions.
      The results show that F, R, and E were not significantly different in normal and
      pathologic legs at rest. The values of F and R were significantly higher in
      pathologic than in normal lower limbs, ten minutes after exercise, whereas E was
      not significantly altered by exercise at any side. This suggests that, during the
      recovery from a walk test, the delayed increase in oxygen uptake is proportional
      to the delayed hyperemia in the ischemic muscles ("oxygen debt") and probably not
      linked to a luxury perfusion.

PMID- 8873586
TI  - Postphlebitic syndrome: clinical activity and tolerability of desmin, new LMW
      dermatan sulfate.
AB  - One hundred patients suffering from postphlebitic syndrome of the lower limbs
      were enrolled in an open, randomized, and multicenter (six centers) trial for a
      period of eighteen months. Patients were randomly assigned to three treatment
      groups to receive (for ninety consecutive days) Desmin, a new low-molecular
      weight dermatan sulfate, at the dose, respectively, of 100 mg once daily by
      subcutaneous (SC) route (36 patients), 100 mg twice a day by SC route (33
      patients), and 200 mg once daily by intramuscular (IM) route (31 patients). The
      general and local tolerability and the clinical efficacy of the drug were
      evaluated by means of clinical, instrumental, and laboratory parameters. Desmin
      is effective in the decompensation stage of postphlebitic syndrome; this was
      demonstrated by a significant reduction in the severity of a number of typical
      symptoms as well as by the drug's positive effect on venous tone as confirmed by
      phlebotensiometric examination. The daily dose of 200 mg (either SC or IM) was
      more effective than the 100 mg dose. The results obtained at the end of the trial
      (ninety days) were statistically better than those obtained after thirty days of
      treatment. This trial demonstrated that both the systemic and the local (at the
      site of injection) tolerability of the drug, administered for three months, were
      good and without significant variations in the laboratory parameters monitored.

PMID- 8873587
TI  - Risk factors for brain infarction in patients with Cushing's disease. Case
      reports.
AB  - Two women aged 51 and 52 years old, respectively, developed a brain infarction
      before and after undergoing treatment for Cushing's disease. A biochemical
      remission was obtained more than ten years after the onset of signs or symptoms
      of Cushing's disease. The arteriosclerotic changes of the cerebral vessels
      progressed even during replacement therapy for posttreatment hypopituitarism
      after they underwent either ablative surgery or radiotherapy. One patient, who
      showed the signs of Nelson's syndrome, demonstrated severe progressive
      cerebrovascular sclerotic changes, especially around the irradiated site. It is
      thus suggested that hypercortisolemia, external pituitary irradiation, and
      posttreatment hypopituitarism may be risk factors for brain infarction. The early
      diagnosis and adequate treatment are therefore important to prevent
      cerebrovascular complications in patients with Cushing's disease.

PMID- 8873588
TI  - 2-D time-of-flight (TOF) MRA of thrombophlebitis of upper extremity and
      subclavian veins. A case report.
AB  - In this report, the authors present a case of segmental thrombosis of left
      subclavian vein that was inaccessible to conventional venography and inconclusive
      in magnetic resonance techniques (spin echo, gradient echo) but was clearly
      demonstrated by two-dimensional time-of-flight magnetic resonance angiography (2D
      TOF MRA). This technique is very sensitive to detect slow flow or partial
      occlusion of the vessels and is of great help in solving the problem of axillary
      subclavian venous obstruction or thrombophlebitis.

PMID- 8873589
TI  - Hemitruncus presenting in an adult. A case report.
AB  - Hemitruncus is a rare congenital anomaly in which one pulmonary artery branch,
      usually the right, arises from the ascending aorta just above the aortic sinuses,
      whereas the main pulmonary artery and the other pulmonary branch arise in their
      normal position. The authors present a case in which the patient was diagnosed as
      having hemitruncus as an adult, and to the best of their knowledge only 7 similar
      cases have been reported in the medical literature.

PMID- 8873590
TI  - Structural changes in the peptide backbone in complex formation between activated
      rhodopsin and transducin studied by FTIR spectroscopy.
AB  - Structural changes in the complex formation between transducin and metarhodopsin
      II, the activated form of photolyzed rhodopsin, in visual transduction processes
      were analyzed by Fourier transform infrared spectroscopy. The spectrum of the
      complex was obtained by subtracting the contribution of metarhodopsin I and
      uncomplexed metarhodopsin II. The averaged spectrum upon the complex formation
      was then compared with that in the conversion of rhodopsin-to-metarhodopsin II.
      Frequency shifts of the peptide carbonyl vibrations at 1686, 1674, and 1661 cm-1
      to 1640 cm-1 were observed upon complex formation from metarhodopsin II plus
      transducin. These changes must have resulted from the strengthening of H-bonding
      of one or a few peptide groups but is not ascribable to global conformation
      change. Changes in the frequencies of the peptide amides were also detected. With
      regard to intramembrane carboxylic acid residues, no further changes were noticed
      in the carboxyl vibrations of Asp83, Glu122, and Glu113. Only a small change
      possibly due to Glu134 was detected.

PMID- 8873591
TI  - Defining protein-protein interactions using site-directed spin-labeling: the
      binding of protein kinase C substrates to calmodulin.
AB  - EPR spectroscopy was used to examine protein-protein interactions between
      calmodulin and spin-labeled peptides based on the protein kinase C substrate
      domains of the myristoylated alanine rich C kinase substrate (MARCKS) and
      neuromodulin. When bound to calmodulin, the C- and N-terminal ends of a 25
      residue MARCKS derived peptide exhibited large amplitude motion on the nanosecond
      time scale and were accessible to paramagnetic agents in aqueous solution.
      However, residues 5-23 were highly protected and in contact with side chains from
      calmodulin. These data are consistent with an alpha-helical configuration for
      this segment of MARCKS and with structures that have been obtained for other
      calmodulin-substrate complexes. For the 17 residue neuromodulin derived peptide,
      which is Ca2+ independent in its binding to calmodulin, oxygen collision rates
      demonstrate that one helical face of this peptide interacts strongly with
      calmodulin. The data are consistent with an interaction of this face specifically
      with the C-terminal lobe of calmodulin, where this lobe is either in an "open" or
      "semiopen" configuration. The EPR data also indicate that the N-terminal lobe of
      calmodulin is in contact with the peptide, but that this lobe is not as strongly
      associated with the peptide target. Overall, the binding pocket for neuromodulin
      appears to be less compact and more dynamic than that formed by MARCKS. This
      behavior has not previously been seen for calmodulin substrates, and it may play
      a role in the Ca2+ independent binding of this class of substrates. This work
      demonstrates the utility of EPR spectroscopy to define protein-protein
      interactions; in addition, oxygen collision frequencies obtained at buried sites
      appear to provide information on the conformational dynamics of proteins.

PMID- 8873592
TI  - Palmitoylation of endothelial nitric oxide synthase is necessary for optimal
      stimulated release of nitric oxide: implications for caveolae localization.
AB  - Endothelial nitric oxide synthase (eNOS) is dually acylated by N-myristoylation
      and cysteine palmitoylation and resides in Golgi and caveolae membranes. N
      Myristoylation is necessary for its membrane association and targeting into the
      Golgi complex of transfected cells whereas palmitoylation influences the
      targeting of eNOS into caveolae. However, the in vivo significance of
      palmitoylation, membrane association, and the corresponding caveolar localization
      of eNOS have not been shown. To further examine the nature of membrane
      association of palmitoylation-deficient forms of eNOS and to address the
      functional role(s) of palmitoylation in activation of eNOS in vivo, HEk 293 cells
      stably transfected with wild-type (WT) or palmitoylation-deficient mutants of
      eNOS were generated. Membrane association of the mutants was biochemically
      similar to that of the WT protein in terms of their resistance to high salt, high
      pH, and distribution between Triton X-114 detergent and aqueous phases,
      suggesting that other hydrophobic factor (s) in eNOS most likely contribute to
      its membrane association. Most importantly, palmitoylation-deficient mutants of
      eNOS released less NO from the cells than did WT enzyme, suggesting that
      palmitoylation plays an important role in determining the optimal release of NO
      from intact cells. The diminished release of NO from the palmitoylation-deficient
      mutants was not attributable to alterations in its catalytic properties as the
      purified mutant and WT enzymes were kinetically identical. Since palmitoylation
      is necessary for localization of eNOS in caveolae, our data suggest that such
      localization could regulate the frequency and magnitude of NO release in response
      to stimuli in vivo.

PMID- 8873593
TI  - A zinc binding site in viral serine proteinases.
AB  - The NS3 protein of hepatitis C virus contains a chymotrypsin-like serine
      proteinase domain. We built a homology model of this domain which predicts the
      presence of a tetradentate metal binding site formed by three cysteines and one
      histidine. These residues are strictly conserved in all known hepatitis C viral
      genotypes as well as in other recently discovered related hepatitis viruses. We
      show that the hepatitis C virus enzyme does indeed contain a Zn2+ ion with S3N
      ligation and that the metal is required for structural integrity and activity of
      the enzyme. Strikingly, the residues forming the metal binding site are also
      conserved in the chymotrypsin-like 2A cysteine proteinases of picornaviruses.
      Remarkably, in these highly variable viral genomes the metal binding site is more
      conserved than the catalytic residues and thus allows us to define a novel class
      of zinc binding chymotrypsin-like proteinases and to identify a new attractive
      target for antiviral therapy.

PMID- 8873594
TI  - Identification of histidine as an axial ligand to P700+.
AB  - The primary electron donor in photosystem I (PSI), P700, is thought to be a
      dimeric Chl a species. Neither the electronic nor geometric structure of the
      cation radical is clearly understood. Magnetic resonance studies have indicated
      that the unpaired electron in P700+ is delocalized asymmetrically over the Chl
      dimer; however, the axial ligand to the central Mg2+ is not known. The recent
      development of a histidine tolerant mutant of Synechocystis PCC 6803 has allowed
      us to use a combination of isotopic labeling and electron nuclear double
      resonance (ENDOR) spectroscopy to show the first definitive spectroscopic
      evidence of a histidine ligand to P700+. Peaks split symmetrically about the 15N
      Larmor frequency corresponding to an isotropic hyperfine coupling of 0.64 MHz
      were observed in the ENDOR spectra from P700+ globally labeled with 15N and
      specifically labeled with [15N]histidine. These peaks disappeared in "reverse"
      labeled samples in which all nitrogens are 15N except those of histidine, which
      contains natural abundance 14N. The dipolar contribution to the hyperfine
      coupling was determined by using electron spin echo envelope modulation
      spectroscopy (ESEEM). Numerical simulations of the ESEEM data suggest that the
      coupling is primarily isotropic and that the histidine is directly coordinated to
      the central Mg2+ of P700+. Taken together, these data are supportive of a model
      of P700+ in which the excited state molecular orbital makes a significant
      contribution to the electronic structure of the radical. Moreover, the
      methodology developed in this work can be extended to examine the magnetic
      properties of axial ligands in a variety of biologically relevant
      porphyrin/chlorin systems.

PMID- 8873595
TI  - Interaction of pyridine nucleotide substrates with Escherichia coli
      dihydrodipicolinate reductase: thermodynamic and structural analysis of binary
      complexes.
AB  - E. coli dihydrodipicolinate reductase exhibits unusual nucleotide specificity,
      with NADH being kinetically twice as effective as NADPH as a reductant as
      evidenced by their relative V/K values. To investigate the nature of the
      interactions which determine this specificity, we performed isothermal titration
      calorimetry to determine the thermodynamic parameters of binding and determined
      the three-dimensional structures of the corresponding enzyme-nucleotide
      complexes. The thermodynamic binding parameters for NADPH and NADH were
      determined to be Kd = 2.12 microM, delta G degree = -7.81 kcal mol-1, delta H
      degree = -10.98 kcal mol-1, and delta S degree = -10.5 cal mol-1 deg-1 and Kd =
      0.46 microM, delta G degree = -8.74 kcal mol-1, delta H degree = -8.93 kcal mol
      1, and delta S degree = 0.65 cal mol-1 deg-1, respectively. The structures of
      DHPR complexed with these nucleotides have been determined at 2.2 A resolution.
      The 2'-phosphate of NADPH interacts electrostatically with Arg39, while in the
      NADH complex this interaction is replaced by hydrogen bonds between the 2' and 3'
      adenosyl ribose hydroxyls and Glu38. Similar studies were also performed with
      other pyridine nucleotide substrate analogs to determine the contributions of
      individual groups on the nucleotide to the binding affinity and enthalpic and
      entropic components of the free energy of binding, delta G degree. Analogs
      lacking the 2'-phosphate containing homologs. For all analogs, the total binding
      free energy can be shown to include compensating enthalpic and entropic
      contributions to the association constants. The entropy contribution appears to
      play a more important role in the binding of the nonphosphorylated analogs than
      in the binding of the phosphorylated analogs.

PMID- 8873596
TI  - DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor
      groove by ecteinascidin 743, a potent antitumor compound from the Caribbean
      tunicate Ecteinascidia turbinata.
AB  - Ecteinascidin 743 is one of several related marine alkaloids isolated from the
      Caribbean tunicate Ecteinascidia turbinata. It is remarkably active and potent in
      a variety of in vitro and in vivo systems and has been selected for development
      as an anticancer agent. The present study investigates the interactions of
      ecteinascidin 743 with DNA. Ecteinascidin 743 retarded the electrophoretic
      migration of both supercoiled and relaxed simian virus 40 DNA even in the
      presence of sodium dodecyl sulfate and after ethanol precipitation, consistent
      with covalent DNA modifications. Similar results were obtained in a DNA
      oligonucleotide derived from ribosomal DNA. However, DNA denaturation reversed
      the DNA modifications. The homopolymeric oligonucleotide dG/dC was modified while
      neither the dI/dC nor the dA/dT oligonucleotides were, consistent with covalent
      attachment of ecteinascidin 743 to the exocyclic amino group at position 2 of
      guanine. Ecteinascidin 743 was then compared to another known DNA minor groove
      alkylating agent, anthramycin, which has also been shown to alkylate guanine N2.
      Footprinting analyses with DNase I and 1,10-phenanthroline-copper and exonuclease
      III digestions showed that ecteinascidin 743 covers three to five bases of DNA
      and exhibits a different sequence specificity than anthramycin in the Escherichia
      coli tyrosine tRNA promoter (tyrT DNA). The binding of ecteinascidin to DNA was
      abolished when guanines were substituted with inosines in this promoter. A band
      shift assay was designed to evaluate the influence of the bases flanking a
      centrally located guanine in an oligonucleotide containing inosines in place of
      guanines elsewhere. Ecteinascidin 743 and anthramycin showed similarities as well
      as differences in sequence selectivity. Ecteinascidin 743-guanine adducts
      appeared to require at least one flanking guanine and were strongest when the
      flanking guanine was 3' to the targeted guanine. These data indicate that
      ecteinascidin 743 is a novel DNA minor groove, guanine-specific alkylating agent.

PMID- 8873597
TI  - Solution structure of an oligodeoxynucleotide duplex containing the exocyclic
      lesion 3,N4-etheno-2'-deoxycytidine opposite 2'-deoxyadenosine, determined by NMR
      spectroscopy and restrained molecular dynamics.
AB  - The d(C-G-T-A-C-epsilon C-C-A-T-G-C).d(G-C-A-T-G-A-G-T-A-C-G)
      oligodeoxynucleotide duplex containing the 3, N4-etheno-2'-deoxycytidine adduct
      positioned opposite 2'-deoxyadenosine in the center of the helix has been
      analyzed by proton NMR spectroscopy and restrained molecular dynamics. The
      spectroscopic data establish a right-handed duplex, with sugar puckers in the C2'
      endo/C3'-exo range, residues adopting an anti conformation around the glycosidic
      torsion angle and, with the exception of epsilon C.dA, Watson-Crick hydrogen bond
      alignment for all base pairs. Molecular dynamics simulations, restrained by the
      full relaxation matrix approach, produced a three-dimensional model with an NMR R
      factor of 7%. The duplex structure shows no significant perturbation of the sugar
      phosphate backbone, which remains in B-form. The exocyclic adduct and its partner
      dA are incorporated into the helix without producing a noticeable kink. The
      epsilon C.dA alignment adopts a staggered conformation with each residue
      displaced toward the 5'-terminus and intercalated between bases on the opposite
      strand, without increase of inter-phosphate distances. The partial intercalation
      of the epsilon C (anti).dA(anti) alignment allows stacking between the aromatic
      rings of epsilon C and dA and with base pairs adjacent to the lesion, suggesting
      an important role played by hydrophobic forces in the stabilization of the
      solution structure.

PMID- 8873598
TI  - NMR solution structure of an oligodeoxynucleotide duplex containing the exocyclic
      lesion 3,N4-etheno-2'-deoxycytidine opposite thymidine: comparison with the
      duplex containing deoxyadenosine opposite the adduct.
AB  - The exocyclic 3,N4-etheno-2'-deoxycytidine adduct was incorporated at the center
      of the oligodeoxynucleotide duplex d(C-G-T-A-C-epsilon C-C-A-T-G-C).d (G-C-A-T-G
      T-G-T-A-C-G), and its solution structure was analyzed using high-resolution
      proton NMR spectroscopy and molecular dynamics simulations. The experimental data
      indicate that the oligodeoxynucleotide duplex adopts a right-handed helical
      structure with sugar puckers in the C2'-endo/C3'-exo range and Watson-Crick
      hydrogen bond alignments for all base pairs. NOE connectivities established a syn
      orientation for the glycosidic torsion angle of the exocyclic adduct. Restrained
      molecular dynamics simulations, using the full relaxation matrix approach,
      produced a three-dimensional model in agreement with the experimental data. The
      structure shows only minor perturbations in the sugar-phosphate backbone and a 27
      degrees bend of the helical axis at the lesion site. On the refined model a well
      formed hydrogen bond between T (N3H) and epsilon C(N4) stabilizes the epsilon
      C(syn).T(anti) base pair alignment, reflecting the preference of the adduct for
      the syn orientation. Furthermore, the epsilon C(syn).T(anti) base pair stacks
      with flanking base pairs. We discuss a correlation between the mutagenic
      properties of the adduct and the three-dimensional structure of the epsilon C.dA
      and epsilon C.T duplexes.

PMID- 8873599
TI  - Alternate-strand triplex formation: modulation of binding to matched and
      mismatched duplexes by sequence choice in the Pu-Pu-Py block.
AB  - In double-stranded DNA, tandem blocks of purines (Pu) and pyrimidines (Py) can
      form triplexes by pairing with oligonucleotides which also consist of blocks of
      purines and pyrimidines, using both Py.Pu.Py (Y-type) and Pu.Pu.Py (R-type)
      pairing motifs in a scheme called "alternate-strand recognition," or ASR
      [Jayasena, S. D., & Johnston, B. H. (1992) Biochemistry 31, 320-327; Beal P. A.,
      & Dervan, P. B. (1992) J. Am. Chem. Soc. 114, 1470-1478]. We investigated the
      relative contributions of the Py.Pu.Py and Pu.Pu.Py blocks in the 16-bp duplex
      sequence 5'-AAGGAGAATTCCCTCT-3' paired with the third-strand oligonucleotides 5'
      TTCCTCTTXXGGGZGZ-3' (XZ-16), where X and Z are either T or A and C is 5
      methylcytosine, using chemical footprinting and get electrophoretic mobility
      shift measurements. We found that the left-hand, pyrimidine half (Y-block) of the
      third strand (TTCCTCTT, Y-8) forms a Py.Pu.Py triplex as detected by both
      dimethyl sulfate (DMS) probing and a gel-shift assay; in contrast, the triplex
      formed by the right-hand half alone (R-block) with X = T (TTGGGTGT, R-8) is not
      detectable under the conditions tested. However, when tethered to the Y-block
      (i.e., as XZ-16), the R-block contributes greatly increased specificity of target
      recognition and confers protection from DMS onto the duplex even under conditions
      unfavorable for Pu-Pu-Py triplexes (lack of divalent cations). In general, the 16
      mer (XZ-16) can bind with apparent strength either greater or lesser than Y-8,
      depending on whether X and Z are A or T. The order of apparent binding strength,
      as measured by the target duplex concentration necessary to cause retardation of
      the third strand during gel electrophoresis, is TT-16 approximately AT-16 > Y-8 >
      AA-16 > TA-16. Chemical probing experiments showed that both halves of the
      triplex form even for AA-16, which binds with less apparent binding strength than
      the pyrimidine block alone (Y-8). The presence of the right half of the 16-mers,
      although detracting from affinity in cases of AA-16 and TA-16, provides strong
      specificity for the correct target compared to a target incapable of forming the
      Pu.Pu.Py part of the triplex. We discuss possible explanations for these
      observations in terms of alternate oligonucleotide conformations and suggest
      practical applications of affinity modulation by A-to-T replacements.

PMID- 8873600
TI  - Triple helical structures involving inosine: there is a penalty for promiscuity.
AB  - Inosine has the ability to act as a "wild-card" binding nonspecifically to both
      A.T and G.C base pairs. This has obvious implications for the design of
      oligonucleotide site-directed probes. In this paper we present a series of
      oligonucleotides with a 5'pur9-pyr9-pyr9 motif which are designed to fold up
      sequentially into intramolecular triple helices. One or more inosines are
      incorporated into the Hoogsteen strands in place of T's and/or C's. Once folded
      into the triplex, the inosine-containing third strand is incorporated in parallel
      orientation to the purine strand of the duplex. The influence of inosine on the
      triplex-duplex equilibrium, characterized by the melting temperature (Tm) and on
      the phase boundaries, as a function of pH and/or ionic strength, has been
      assessed by means of UV and CD spectroscopy. There are two distinguishable
      influences of third-strand inosines which affect binding, namely, backbone
      distortion due to bulkiness (I for T and I for C+) and/or loss of intramolecular
      ion pairs between protonated cytosines and the backbone phosphates (I for C+). A
      single thymine replacement drops the Tm by 25.0 (+/- 2.1) degrees C, and
      replacing a single protonated cytosine drops the Tm by 32.1 (+/- 1.0) degrees C
      at pH 6.0. On introducing two inosines in place of thymines, the Tm at pH 6.0 of
      the triple helix to hairpin transition is lowered by 35.5 (+/- 1.4) degrees C; on
      introducing two inosines in place of cytosines, the Tm drops by 44.5 (+/- 1.0)
      degree C, and on replacing a cytosine and a neighboring thymine with inosines,
      the Tm of the same transition is lowered by 29.2 (+/- 1.6) degrees C. Replacing
      more than two thymines or cytosines, respectively, eliminates the binding of the
      Hoogsteen strand at room temperature altogether. Under no circumstances does
      inosine replacement stabilize the triplex helix: it is a poor substitute and its
      role as a wild-card is limited.

PMID- 8873601
TI  - Antagonist effects of Ca2+ and spermine on phosphatidylinositol 4,5-bisphosphate
      mediated transmembrane redistribution of phospholipids in large unilamellar
      vesicles and in erythrocytes.
AB  - We have previously suggested the involvement of a Ca(2+)-phosphatidylinositol 4,5
      bisphosphate (PIP2) complex in the phospholipid transmembrane redistribution
      triggered by cytosolic Ca2+ in erythrocytes. Indeed, the lipid scrambling was
      induced by extracellular Ca2+ in erythrocytes loaded with PIP2 and was abolished
      in inside-out vesicles prepared from PIP2-depleted erythrocytes (Sulpice, J.C.,
      Zachowski, A., Devaux, P.F., & Giraud, F. (1994) J. Biol. Chem. 269, 6347-6354).
      Here, we show that Ca2+ triggers a partial redistribution of spin-labeled
      phospholipids in protein-free large unilamellar vesicles (LUVs), only when they
      contain PIP2. Spermine, a polyamine known to interact with PIP2 and reported to
      inhibit lipid scrambling in resealed ghosts, was found to inhibit also the Ca(2+)
      induced scrambling in LUVs and in PIP2-loaded erythrocytes, presumably by
      interacting with PIP2 and preventing the formation of Ca(2+)-PIP2 complexes. A
      similar mechanism can account for spermine inhibition in natural membranes,
      confirming the role of PIP2 in the scrambling process without excluding the
      participation of proteins. In erythrocytes, activation of the phosphoinositide
      phospholipase C (PLC) or a 20 h ATP depletion, which both led to a reduction in
      the PIP2 content by 40-60%, did not affect Ca(2+)-induced phospholipid
      scrambling. In contrast, longer ATP depletion, resulting in a 80% reduction in
      the PIP2 content, did induce a significant decrease in lipid scrambling,
      suggesting that only the PIP2 pool resistant to the PLC was involved. Spermine
      was able to inhibit hydrolysis of this pool by an exogenous PLA2. It is thus
      likely that spermine antagonized the Ca(2+)-induced scrambling in resealed ghosts
      by interacting with the PLC-resistant pool of PIP2.

PMID- 8873602
TI  - Cholesterol versus alpha-tocopherol: effects on properties of bilayers made from
      heteroacid phosphatidylcholines.
AB  - The techniques of differential scanning calorimetry, fluorescence of merocyanine
      540, fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene, proton
      permeability, and lipid peroxidation are used to compare the perturbations of
      cholesterol and alpha-tocopherol on lipid bilayer membranes composed of different
      phosphatidylcholines containing stearic acid in the sn-1 position and an
      unsaturated fatty acid (either oleic, alpha-linolenic, gamma-linolenic, or
      docosahexaenoic acid) in the sn-2 position. It is concluded that the structural
      roles of cholesterol and alpha-tocopherol may be similar with membranes composed
      of some phosphatidylcholines but are clearly different with membranes composed of
      other related phosphatidylcholines. alpha-Tocopherol exerts a much larger effect
      than cholesterol on membranes rich in polyunsaturated fatty acids that have their
      initial double bond before the delta 9 position. Cholesterol interacts more
      favorably with fatty acids that do not have an double bond before the delta 9
      position. The membrane structural effects are explained in terms of the larger
      size of the sterol ring structure of cholesterol compared to the smaller
      chromanol ring of the alpha-tocopherol.

PMID- 8873603
TI  - Chemical rescue of Asp237-->Ala and Lys358-->Ala mutants in the lactose permease
      of Escherichia coli.
AB  - Asp237 (helix VII) and Lys358 (helix XI) form a salt bridge in the lactose
      permease, and neutral replacement of either residue inactivates. Remarkably,
      noncovalent neutralization of the unpaired Asp or Lys residue, respectively, with
      n-alkylsulfonates or n-alkylamines of appropriate size restores active transport
      to high levels in the mutants. Saturation with respect to the concentration of
      the alkylamines and different size preferences suggest that the alkylamines bind
      sterically at position 358. Rescue of Asp237-->Ala by alkylsulfonates is
      apparently more indiscriminate, since methane-, ethane-, or propane-sulfonate
      have comparable effects. Sodium and chloride, respectively, are also effective in
      rescuing the Lys358-->Ala and Asp237-->Ala mutants, while various other compounds
      are ineffective. In marked contrast to Asp237-->Ala or Lys358-->Ala permease,
      alkylsulfonates or alkylamines have no effect whatsoever on the activity of
      mutants with neutral replacements for Asp240, Glu269, Arg302, Lys319, His322, or
      Glu325. The results support the conclusion that neutral replacement of one member
      of the charge pair between Asp237 and Lys358 leads to inactivation because of an
      unpaired charge in the low dielectric of the membrane. In addition, the findings
      are consistent with the idea that interactions between Arg302 and Glu325, His 322
      and Glu269, and Asp240 and Lys319 play important roles in the mechanism of the
      permease, which is not the case for either Asp237 or Lys358 or the salt bridge
      between the two residues.

PMID- 8873604
TI  - Na+ ions binding to the bradykinin B2 receptor suppress agonist-independent
      receptor activation.
AB  - Control of the balance between receptor activation and inactivation is a
      prerequisite for seven transmembrane domain (7TM) receptor function. We asked for
      a mechanism to stabilize the inactive receptor conformation which prevents
      agonist-independent receptor activation. Na+ ions have reciprocal effects on
      agonist versus antagonist interaction with various 7TM receptors. To investigate
      the Na+ dependence of receptor activation we chose the bradykinin B2 receptor as
      a prototypic 7TM receptor. Decrease of the intracellular Na+ content from 40 mM
      to 10 mM of COS-1 cells transiently expressing rat B2 receptors activated the B2
      receptor in the absence of agonist as shown by a 3-fold increase in the basal
      release of inositolphosphates and increased the intrinsic activity of bradykinin
      to 1.2. In contrast, under increased intracellular Na+ (148 mM) the intrinsic
      activity of bradykinin decreased to 0.72. When the interaction of Na+ with the B2
      receptor was prevented by exchanging a conserved aspartate in transmembrane
      domain II for asparagine the B2 receptor was also constitutively-activated in the
      absence of agonist. Agonist-independence B2 receptor activation under decreased
      intracellular Na+ was similarly observed with primary human fibroblasts
      endogenously expressing human B2 receptors by a 2.5-fold increase in basal
      inositolphosphates. Activation of human B2 receptors in the absence of agonist
      under decreased intracellular Na+ was further evident by an increased basal
      phosphorylation of the B2 receptor protein. Thus our data suggest that the
      interaction of Na+ ions with the B2 receptor stabilizes or induces an inactive
      receptor conformation thereby providing a mechanism to suppress agonist
      independent receptor activation in vivo.

PMID- 8873605
TI  - Temperature-induced denaturation of ribonuclease S: a thermodynamic study.
AB  - In this paper the thermal denaturation of ribonuclease S, the product of mild
      digestion of ribonuclease A by subtilisin, is deeply investigated by means of DSC
      and CD measurements. It results that at whatever pH in the range 4-7.5 the
      process if fully reversible but not well represented by the simple two-state N<-
      >D transition. Actually, a two-state model that considers both unfolding and
      dissociation, NL<-->D + L*, well accounts for the main features of the process:
      the tail present in the low-temperature side of DSC peaks and the marked
      dependence of denaturation temperature on protein concentration. This mechanism
      is strictly linked to the exact stoichiometry of RNase S. An excess of the
      protein component of RNase S, the so-called S-protein, shifts the system toward a
      more complex behavior, that deserves a separate treatment in the accompanying
      paper [Graziano, G., Catanzano, F., Giancola, C., & Barone, G. (1996)
      Biochemistry 35, 13386-13392]. The thermodynamic analysis leads to the conclusion
      that the difference in thermal stability between RNase S and RNase A is due to
      entropic effects, i.e., a greater conformational flexibility of both backbone and
      side chains in RNase S. The process becomes irreversible at pH 8.0-8.5, probably
      due to side-reactions occurring at high temperature. Finally, the influence of
      phosphate ion on the stability of RNase A and RNase S at pH 7.0 is studied and
      explained in terms of its binding on the active site of ribonuclease. The
      analysis enables us to obtain an estimate of the apparent association constant
      and binding enthalpy also.

PMID- 8873606
TI  - DSC study of the thermal stability of S-protein and S-peptide/S-protein.

PMID- 8873607
TI  - Phospholamban-dependent effects of C12E8 on calcium transport and molecular
      dynamics in cardiac sarcoplasmic reticulum.
AB  - We have studied the effects of the nonionic detergent C12E8 on Ca-ATPase
      enzymatic activity and oligomeric state (detected by time-resolved
      phosphorescence anisotropy, TPA) in skeletal and cardiac sarcoplasmic reticulum
      (SR). In skeletal, SR, C12E8 inhibits the CA-ATPase, both at high (micromolar and
      above) and low (submicromolar) Ca. In cardiac SR, C12E8 inhibits at high Ca but
      activates at low Ca. Thus C12E8 activates enzymatic activity only in cardiac SR
      and only under conditions (submicromolar Ca) where phospholamban (PLB) regulates
      (inhibits) the enzyme [Lu, Y.-Z., & Kirchberger, M.A. (1994) Biochemistry 33,
      5056-5062]. TPA of skeletal SR at low and high Ca demonstrates that C12E8 induces
      aggregation of ATPase monomers and small oligomers. C12E8 also aggregates the Ca
      ATPase in cardiac SR at high Ca. In cardiac SR at low Ca, the Ca-ATPase is
      already highly aggregated, and C12E8 partially dissociates these aggregates. Thus
      the TPA results provide a simple physical explanation for the functional effects:
      C12E8 inhibits the ATPase when it aggregates the enzyme (skeletal SR at high and
      low Ca; cardiac SR at high Ca), and the detergent activates when it dissociates
      ATPase oligomers (cardiac SR at low Ca). C12E8 stabilizes the E2P conformation of
      the Ca-ATPase with respect to the E2 conformation, and this stabilization is PLB
      dependent. Both the physical and functional effects of C12E8 on the Ca-ATPase are
      PLB-dependent, with C12E8 reversing the effects of PLB. The results provide
      insight into the mechanism by which PLB regulates the Ca-ATPase in cardiac SR.

PMID- 8873608
TI  - Electron transfer across the O2- generating flavocytochrome b of neutrophils.
      Evidence for a transition from a low-spin state to a high-spin state of the heme
      iron component.
AB  - The NADPH oxidase complex of activated neutrophils consists of a membrane-bound
      flavocytochrome b and cytosolic activation factors. Despite its ability to react
      with O2, the heme b component of the flavocytochrome is insensitive to cyanide
      and CO2, and slowly reactive to butyl isocyanide. We report here that arachidonic
      acid, an anionic amphophil which elicits oxidase activation in a cell-free system
      induces a transition of the heme iron of the neutrophil flavocytochrome b from a
      low-spin hexacoordinated state to a high-spin pentacoordinated state and promotes
      the binding of butyl isocyanide to the heme b. Low-temperature EPR spectra of air
      oxidized flavocytochrome b either purified or in its membrane-bound form showed a
      low-spin signal at g = 3.26 and a high-spin signal at g = 6.0. Upon addition of
      arachidonic acid, the g = 3.26 signal vanished; a low-spin signal at g = 2.23
      appeared, and the signal at g = 6.0 progressively increased. The subsequent
      addition of butyl isocyanide resulted in the decrease of the g = 6.0 and g = 2.23
      signals and in the appearance of a new low-spin signal at g = 2.33. Consistent
      with the EPR results, upon addition of arachidonic acid to oxidized
      flavocytochrome b, a 2.5 nm blue shift of the Soret peak was detected in low
      temperature optical spectra. The subsequent addition of butyl isocyanide resulted
      in the emergence of a peak at 432 nm reflecting the formation of a butyl
      isocyanide-oxidized heme b complex. In the case of sodium dithionite-reduced
      flavocytochrome b, arachidonic acid promoted the binding of butyl isocyanide to
      the reduced heme b, as shown by the emergence of a peak at 434 nm and the
      decrease of the alpha band at 558 nm. The same promoting effect was encountered
      with sodium dodecyl sulfate, an anionic amphophil capable of eliciting oxidase
      activation like arachidonic acid. In contrast to arachidonic acid, arachidonic
      acid methyl ester was ineffective and counteracted the effect of arachidonic
      acid. Butyl isocyanide added to intact neutrophils was found to bind to heme b,
      only after the cells have been activated. These data demonstrate the transient
      accumulation of a pentacoordinated form of the heme iron of flavocytochrome b
      under in vitro and in vivo conditions; the pentacoordinated form of the reduced
      heme b is postulated to react with O2 to generate the superoxide anion.

PMID- 8873609
TI  - Electron transfer in tetrahemic cytochromes c3: spectroelectrochemical evidence
      for a conformational change triggered by heme IV reduction.
AB  - Electron transfer in tetrahemic cytochromes c3 from Desulfovibrio vulgaris
      Hildenborough (D.v.H.) and Desulfovibrio desulfuricans Norway (D.d.N.) strains
      has been investigated by thin layer spectroelectrochemistry with visible
      absorption, CD, and resonance Raman (RR) monitoring. The observed splitting of
      the isosbestic point in the Soret absorption band indicates that the electron
      transfer from the (FeIII)4 state to the (FeII)4 state proceeds via an
      intermediate species, which corresponds to 25 and 50% reduction for the D.v.H.
      cyt.c3 and the D.d.N. cyt.c3, respectively. For the latter, a specific CD signal
      is observed at half-reduction. RR monitoring of the redox process does not reveal
      multiple splitting of the high-frequency RR bands, at variance with previously
      published results on the enzymatic reduction of cyt.c3 from Desulfovibrio
      vulgaris Miyazaki, a cytochrome highly homologous to D.v.H. cyt.c3 [Verma, A.L.,
      Kimura, A., Nakamura, A., Yagi, T., Inoguchi, H., & Kitagawa, T. (1988) J. Am.
      Chem. Soc. 110, 6617-6623]. The low-frequency RR spectra of the intermediate
      species differ significantly from the ones calculated from a linear combination
      of the all-ferric and all-ferrous states, for the same reduction ratio. Frequency
      shifts of the bending modes of the cysteine and propionate heme substituents are
      observed, as well as changes specific to each cytochrome; most notable is the
      activation of two torsional modes in the case of D.d.N. cyt.c3. Comparison of the
      results obtained for the two cytochromes leads to the conclusion that reduction
      of heme IV triggers the observed conformational change. This conclusion is
      supported by the spectroelectrochemical investigation of the mutant D.v.H. cyt.c3
      H25M, in which the sixth ligand of heme III, histidine, is replaced by a
      methionine.

PMID- 8873610
TI  - Luminal pH regulated calcium release kinetics in sarcoplasmic reticulum vesicles.
AB  - Calcium binding to triads isolated from rabbit skeletal muscle followed a single
      hyperbolic function in the pH range 5.5-8.0. Maximal binding was obtained at pH
      8.0; decreasing the pH decreased the binding capacity and, at pH < or = 6.0,
      increased Kd 2-fold. These results indicate that lowering the pH diminished
      calcium binding to calsequestrin, since this protein is the primary source of
      calcium binding sites in triads. Luminal pH had a marked effect on calcium
      release induced by 2 mM ATP, at pCa 5.0, pH 6.8. At a constant luminal [Ca2+] of
      0.1 mM, release rate constants (k) and initial rates of release increased
      steadily as a function of decreasing luminal pH; at luminal pH 7.5, values of k <
      0.4 s-1 were found, whereas at pH 5.5 values of k approximately 10 S-1 were
      obtained. Increasing luminal [Ca2+] from 0.05 mM to 0.7 mM had no effect on the k
      values measured at luminal pH 5.5. In contrast, at pH 6.8, increasing luminal
      [Ca2+] produced a marked increase in k values, that reached maximal values of k
      approximately 10 S-1 at 0.7 mM luminal [Ca2+]. Control experiments using
      fluorescent pH indicators showed that luminal pH did not change significantly
      during calcium release. It is proposed that luminal protons or calcium induces
      conformational changes in calsequestrin that in turn promote activation of the
      calcium release channels.

PMID- 8873611
TI  - Tubulin conformation and dynamics: a red edge excitation shift study.
AB  - The fluorescence emission maximum of a polar fluorophore in viscous medium often
      shows a dependence on excitation wavelength, a phenomenon which is named red edge
      excitation shift (REES). We have found that the fluorescence spectra of the
      tubulin tryptophans exhibit a REES of about 7 nm. Also, their steady state
      fluorescence polarization and mean lifetimes show a dependence on both excitation
      and emission wavelengths. These results indicate that the average tryptophan
      environment in tubulin is motionally restricted. Although the tryptophan(s)
      responsible for the observed REES effect could not be localized, it could be
      concluded from energy transfer experiments with the tubulin-colchicine complex
      that the tryptophan(s) participating in energy transfer with bound colchicine
      probably does not contribute to the REES. A REES of 7 nm was also observed in the
      case of colchicine complexed with tubulin. However, such a REES was not seen in
      similar studies with the B-ring analogs of colchicine, viz. 2-methoxy-5-(2',3',4'
      trimethoxyphenyl)tropone (called AC because it lacks the B ring of colchicine)
      and deacetamidocolchicine (which lacks the acetamido substituent at the C-7
      position of the B ring). There may be two possible reasons to explain these data.
      (1) Structural differences between colchicine and its analogs may give rise to
      differences in their excited state dipole moments which will directly affect the
      extent of REES, and (2) The B-ring substituent, hanging outside the colchicine
      binding site on the beta-subunit of the tubulin dimer, probably makes contact
      with the alpha-subunit of tubulin and imparts a rigidity to that region of the
      protein, which facilitates the REES.

PMID- 8873612
TI  - Partial unfolding and refolding of scrapie-associated prion protein: evidence for
      a critical 16-kDa C-terminal domain.
AB  - The conversion of the normal form of prion protein (PrPC) to a disease-specific
      form (PrPSc) is a central event in scrapie and other transmissible spongiform
      encephalopathies. PrPSc is distinguished from PrPC by its insolubility and its
      resistance to proteolysis. PrPSc is also capable of converting 35S-PrPC, in
      vitro, into a form which is indistinguishable from PrPSc with respect to its
      protease-sensitivity. Both the "converting activity" and the protease-resistance
      of isolated hamster PrPSc can be at least partially eliminated by denaturation
      and recovered by renaturation, provided that the concentration of denaturant does
      not exceed a threshhold. This study was undertaken in order to localize the
      regions of native PrPSc structure that must remain intact to allow refolding.
      Proteinase K was used to digest exposed, denatured PrPSc sequences, and the
      residual fragments were characterized using anti-PrP antibodies directed toward
      four PrP epitopes. A 16-kDa fragment marked by an epitope within residues 143-156
      remained protease-resistant under conditions which at least partially unfolded
      epitopes within residues 90-115 and 217-232. However, dilution of denaturant
      restored protease-resistance to these epitopes. This reversible unfolding was
      observed with both purified PrPSc and PrPSc in crude brain homogenates. Size
      fractionation of partially GdnHCl-solubilized PrPSc revealed that only the
      insoluble aggregates retained the ability to refold, consistent with the
      hypothesis that native PrPSc is an ordered aggregate. When the threshold
      denaturant concentration was exceeded, both protease-resistance of the 16-kDa C
      terminal domain and converting activity were irreversibly destroyed. These
      results suggest that the in vitro converting activity requires ordered, protease
      resistant PrPSc aggregates and that a critical aspect of the PrPSc structure is
      the folding of a particularly stable approximately 16-kDa C-terminal domain.

PMID- 8873613
TI  - Effect of geldanamycin on the kinetics of chaperone-mediated renaturation of
      firefly luciferase in rabbit reticulocyte lysate.
AB  - Renaturation of thermally denatured firefly luciferase in rabbit reticulocyte
      lysate (RRL) requires hsp90, hsc70, and other as yet unidentified RRL components
      [Schumacher, R.J., et al. (1994) J. Biol. Chem. 269, 9493-9499]. Benzoquinonoid
      ansamycins (BAs) have recently been shown to specifically bind hsp90 and inhibit
      its function. In this report, we present data that indicate BAs are specific
      inhibitors of hsp90 function. The effects of the BA geldanamycin (GA) on the
      kinetics of the luciferase renaturation in RRL were examined to gain insight into
      the mechanism by which GA inhibits the function of the hsp90 chaperone machinery.
      Chaperone-mediated renaturation of luciferase obeyed Michaelis-Menten kinetics.
      The GA inhibited luciferase renaturation uncompetitively with respect to ATP
      concentration and noncompetitively with respect to luciferase concentration,
      indicating that GA binds after the binding of ATP and that it binds to both the
      hsp90 chaperone machine/ATP complex and the hsp90 chaperone
      machine/ATP/luciferase complex. GA markedly decreased the Kapp of the hsp90
      chaperone machine for ATP, suggesting that GA increases the binding affinity of
      the hsp90 chaperone machinery for ATP or it slows the rate of ATP hydrolysis.
      Consistent with the notion that GA specifically binds hsp90 and inhibits its
      function, addition of hsp90, but not hsc70, p60, or p23, reversed GA-induced
      inhibition of luciferase renaturation in RRL. Hsp90, hsc70, and the hsp cohorts
      p60, p48, and p23 were coimmunoprecipitated with luciferase from RRL. GA
      increased the steady-state levels of luciferase associated with hsp90/hsp70
      chaperone machine complexes that contain p60 and blocked the association of the
      hsp90 cohort p23 with chaperone-bound luciferase. The data suggest that the
      function of the hsp90 chaperone machinery is not specific to its previously
      described interaction with steroid hormone receptors, and that it carries out
      some more generalized function in vivo.

PMID- 8873614
TI  - Hsp90-mediated folding of the lymphoid cell kinase p56lck.
AB  - Several lines of evidence suggest that members of the 90-kDa family of heat shock
      proteins (hsp90) may support the folding of various homologues of the src kinase
      family. In this work, we utilized pulse-chase analyses in rabbit reticulocyte
      lysate to demonstrate that hsp90-bound intermediates existed for the majority of
      newly synthesized p56lck molecules. The hsp90-binding drug geldanamycin disrupted
      the association of p56lck with hsp90, prevented the kinase from demonstrating a
      protease-resistant conformation, and caused decreases in kinase specific
      activity. Requirements for geldanamycin-inhibitable hsp90 function and physical
      interactions between hsp90 and p56lck persisted during chase periods. Consistent
      with the effects observed in rabbit reticulocyte lysate, application of
      geldanamycin to fibroblasts caused specific reversion of lck-mediated
      transformation concomitant with loss of p56lck activity and protein. However,
      geldanamycin had no direct effect on purified p56lck. Also consistent with
      functional linkages between hsp90 and p56lck, physical interactions between these
      proteins were detected in cytoplasmic, but not membrane, fractions of LSTRA
      cells. Although hsp90 functions in both the initial de novo folding and the
      reiterative support of p56lck structure in rabbit reticulocyte lysate, the
      specific occurrence of complexes between hsp90 and p56lck in the cytoplasm of T
      cells suggests that hsp90 primarily folds nascent molecules of p56lck in vivo.

PMID- 8873615
TI  - Analysis of the structure and function of the von Willebrand factor A1 domain
      using targeted deletions and alanine-scanning mutagenesis.
AB  - von Willebrand factor (vWF) mediates the primary adhesion of platelets to sites
      of vascular damage through interaction with glycoprotein Ib (GPIb) of the
      platelet GPIb/IX complex. To investigate the vWF/GPIb interaction we introduced
      both in-frame deletions and substitutions into the vWF A1 domain. The
      introduction of nine sequential 20-amino acid deletions within the Cys509-Cys695
      loop of the A1 domain caused the defective secretion of vWF from mammalian cells,
      and resulted in multimeric vWF without platelet-binding activity. In other
      experiments we substituted alanine for charged amino acids (residues 524, 534,
      549, 552, 569-573, and 642-645) in proposed functional domains within the Cys509
      Cys695 loop. All six substitution mutants showed normal secretion from
      transfected mammalian cells and bound to fixed platelets in the presence of
      botrocetin. In contrast, only mutants vWF-R524A and vWF-K549A showed significant
      binding to platelets in the presence of ristocetin. Mutant vWF-K549A showed
      increased platelet-binding at suboptimal concentrations of both botrocetin and
      ristocetin. These results suggest that the substituted amino acids do not play a
      critical role in the activation of vWF by botrocetin or in the direct interaction
      of vWF with the GPIb/IX complex. However, the charged amino acids at positions
      534, 552, 569-573, and 642-645 do play an important role in the ristocetin
      induced binding of vWF to platelets. The interaction of vWF with heparin was
      significantly reduced by substitution of Lys residues 642-645, indicating that
      these residues may form part of a heparin-binding domain in the carboxy-terminal
      half of the Cys509-Cys695 loop.

PMID- 8873616
TI  - Analysis of rate-determining conformational changes during self-splicing of the
      Tetrahymena intron.
AB  - RNA catalyzed reactions are often limited in vitro by the rate of structural
      rearrangements in the RNA. Analysis of intra- and intermolecular splicing of the
      Tetrahymena preribosomal RNA revealed two well resolved kinetic phases with rate
      constants of approximately 2.5 and 0.02 min-1 at 30 degrees C. The data are
      consistent with a model in which the second phase results from slow refolding of
      the pre-rRNA. Point mutations result in redistribution of the RNA among different
      conformations that can be detected by native gel electrophoresis. The active pre
      rRNA rapidly progresses to a product complex in the presence of GTP. Release of
      the ligated exons is slightly slower than splicing at 30 degrees C (0.3 -0.5 min
      1). In contrast, the intermediate complex after the first step of splicing
      dissociates much more slowly (5 x 10(-3) min-1), accounting for the low amount of
      intron-3' exon intermediate typically seen during splicing of wild type pre-rRNA.
      These results provide an initial framework for studying conformational changes
      that accompany excision of the Tetrahymena intron from ribosomal RNA.

PMID- 8873617
TI  - Determination of the chemical pathway for 4-chlorobenzoate:coenzyme A ligase
      catalysis.
AB  - 4-Chlorobenzoate:coenzyme A ligase (4-CBA:CoA ligase) catalyzes the first step of
      the 4-CBA degradation pathway of Pseudomonas sp. strain CBS3. In this reaction, 4
      CBA-CoA thioester synthesis is coupled to ATP cleavage. The studies described in
      this paper examine the intermediacy of 4-chlorobenzoyl-adenosine 5'phosphate
      diester (4-CBA-AMP) in the ligase reaction. The 4-CBA-AMP adduct was isolated
      from the ligase reaction mixture generated from magnesium adenosine 5
      triphosphate (MgATP) and 4-CBA in the absence of CoA. The structure of the 4-CBA
      AMP was verified by 1H- 13C-, and 31P-nuclear magnetic resonance analysis. Single
      turnover reactions carried out with 14C-labeled 4-CBA in a rapid quench apparatus
      demonstrated formation of the enzyme. 4-CBA-AMP.MgPPi complex from the enzyme.4
      CBA.MgATP complex at a rate of 135 s-1. The rate of ligand release from the
      enzyme.4-CBA-AMP.MgPPi complex was measured at 0.013 s-1. Single-turnover
      reactions of [14C]-4-CBA, MgATP, and CoA catalyzed by the ligase revealed that
      the 4-CBA-AMP intermediate formed reaches a maximum level of 25% of the starting
      4-CBA within 10 ms and then declines with the formation of the 4-CBA-CoA. The
      rates of the adenylation and thioesterification partial reactions, determined by
      kinetic simulation of the rate data, are nearly equal (135 and 100 s-1).
      Substitution of CoA with the slow substrate pantetheine did not significantly
      alter the rate of the adenylation step but did reduce the rate of the
      thioesterification step to 2 s-1. The maximum level of 4-CBA-AMP reached during
      the single-turnover reaction of 4-CBA, MgATP, and pantetheine corresponded to one
      half of the starting 4-CBA.

PMID- 8873619
TI  - Involvement of the alpha subunit of farnesyl-protein transferase in substrate
      recognition.
AB  - Using photoaffinity labeling, we have identified a region in mammalian farnesyl
      protein transferase (FPTase) involved in substrate recognition. The photolabel
      used (Compound 1) is a peptide containing the photoactive amino acid p
      benzoylphenylalanine (Bpa). Upon exposure to UV light. Compound 1 inhibits FPTase
      activity in a time- and concentration-dependent manner. Photoinhibition of FPTase
      activity by Compound 1 is prevented by adding H-Ras to the reaction mixture,
      indicating that labeling is targeted to the enzyme active site. We used peptide
      mapping by HPLC, Edman sequencing, and matrix-assisted time-of-flight (MALDI-TOF)
      mass spectrometry to identify the site of interaction with radiolabeled Compound
      1. These experiments indicate that a specific region of the alpha subunit of the
      enzyme, Asp110-Arg112, is involved in substrate binding and suggest that Glu111
      is likely to be the residue covalently modified by the photoaffinity label.
      Sequence alignments between yeast and mammalian FPTases reveal that Glu111 is
      conserved. The implications of this finding are discussed in light of previous
      mutagenesis studies on FPTase.

PMID- 8873618
TI  - A change in the internal aldimine lysine (K42) in O-acetylserine sulfhydrylase to
      alanine indicates its importance in transimination and as a general base
      catalyst.
AB  - O-Acetylserine sulfhydrylase (OASS) is a pyridoxal 5'-phosphate dependent enzyme
      that catalyzes a beta-replacement reaction forming L-cysteine and acetate from O
      acetyl-L-serine (OAS) and sulfide. The pyridoxal 5'-phosphate (PLP) is bound at
      the active site in Schiff base linkage with a lysine. In the present study, the
      Schiff base lysine was identified as lysine 42, and its role in the OASS reaction
      was determined by changing it to alanine using site-directed mutagenesis. K42A
      OASS is isolated as an external aldimine with methionine or leucine and shows no
      reaction with the natural substrates. Apo-K42A-OASS can be reconstituted with
      PLP, suggesting that K42 is not necessary for cofactor binding and formation of
      the external Schiff base. The apo-K42A-OASS, reconstituted with PLP, shows slow
      formation of the external aldimine but does not form the alpha-aminoacrylate
      intermediate on addition of OAS, suggesting that K42 is involved in the
      abstraction of the alpha-proton in the beta-elimination reaction. The external
      aldimines formed upon addition of L-Ala or L-Ser are stable and represent a
      tautomer that absorbs maximally at 420 nm, while L-Cys gives a tautomeric form of
      the external aldimine that absorbs at 330 nm, and is also seen in the overall
      reaction after addition of primary amines to the assay system. The use of a small
      primary amine such as ethylamine or bromoethylamine in the assay system leads to
      the initial formation of an internal (gamma-thialysine) or external (ethylamine)
      aldimine followed by the slow formation of the alpha-aminoacrylate intermediate
      on addition of OAS. Activity could not be fully recovered, and only a single
      turnover is observed. Data suggest a significant rate enhancement resulting from
      the presence of K42 for transimination and general base catalysis.

PMID- 8873620
TI  - Always sanitary napkins: further reports and manufacturer response.

PMID- 8873622
TI  - University fee for student health services.

PMID- 8873621
TI  - Always sanitary napkins: further reports and manufacturer response.

PMID- 8873623
TI  - Progress in screening for cervical cancer.

PMID- 8873624
TI  - Progress in screening for cervical cancer.

PMID- 8873625
TI  - Urgency in the emergency.

PMID- 8873626
TI  - Urgency in the emergency.

PMID- 8873627
TI  - Urgency in the emergency.

PMID- 8873628
TI  - Urgency in the emergency.

PMID- 8873629
TI  - Behaviour toward residents innocuous or intolerable?

PMID- 8873630
TI  - Behaviour toward residents innocuous or intolerable?

PMID- 8873631
TI  - New drug to prevent NSAID-related ulcers.

PMID- 8873632
TI  - Recent trends in Canadian infant mortality rates: effect of changes in
      registration of live newborns weighing less than 500 g.
AB  - OBJECTIVE: To ascertain whether the increase in the crude infant mortality rate
      in Canada in 1993 was due to a recent increase in the registration of newborns
      weighing less than 500 g as live births. DESIGN: Ecological study, with Poisson
      regression analysis. SETTING: Canada. SUBJECTS: All live births and infant deaths
      in Canada between 1987 and 1993, as reported by Statistics Canada. Data from
      Newfoundland were excluded because they were incomplete for 4 years. OUTCOME
      MEASURES: Proportion of live births by low-birth-weight category; and annual
      crude and adjusted infant mortality rates. RESULTS: Over the study period the
      proportion of newborns weighing less than 500 g registered as live births
      increased significantly (chi 2 for trend = 71.26, p < 0.01). This trend was an
      isolated phenomenon rather than a general increase in all low-birth-weight
      categories (chi 2 for trend in the proportion of newborns weighing 500 to 2400 g
      registered as live births = 1.14, p = 0.28). The crude infant mortality rate per
      1000 live births decreased from 6.4 in 1991 to 6.1 in 1992 and then increased to
      6.3 in 1993. Poisson regression analysis revealed that the apparent increase in
      the infant mortality rate was caused by the increased registration of infants
      weighing less than 500 g as live births. The adjusted infant mortality estimate
      for 1993 was lower than that for 1992. CONCLUSIONS: The increased infant
      mortality rate in Canada in 1993 appears to be due to increased registration of
      infants weighing less than 500 g as live births. Comparisons of infant mortality
      rates by place and time should be adjusted for the proportion of such live
      births, especially if the comparisons involve recent years.

PMID- 8873633
TI  - Management of intermittent claudication with pentoxifylline: meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy of pentoxifylline therapy in improving the
      walking capacity of patients with moderate intermittent claudication. DATA
      SOURCES: A search of MEDLINE for trials published between 1976 and 1994
      inclusive, and a bibliographic review of all articles retrieved. STUDY SELECTION:
      Randomized, placebo-controlled, double-blind clinical trials were selected that
      evaluated the pain-free walking distance (the distanced walked on a treadmill
      before the onset of calf pain) and the absolute claudication distance (the
      maximum distance walked on a treadmill) among patients with moderate intermittent
      claudication. Twelve study groups in 11 trials were included in the analysis.
      DATA EXTRACTION: In addition to information regarding the trial design, patient
      characteristics, dosages and treatment periods, the means and standard deviations
      were collected for both the pain-free walking and absolute claudication
      distances. Trial quality was also assessed. DATA SYNTHESIS: Overall, there was a
      statistically significant improvement in the pain-free walking distance after
      pentoxifylline therapy (weighted mean difference 29.4 m [95% confidence interval
      (CI) 13.0 to 45.9 m]); this finding was based on a total sample of 612 patients
      (308 in the treatment groups and 304 in the control groups). A significant
      improvement was also noted in the absolute claudication distance (weighted mean
      difference 48.4 m [95% CI 18.3 to 78.6 m]); this was based on a total sample of
      511 patients (258 in the treatment group and 253 in the control group). In a
      sensitivity analysis of the pain-free walking distance, significant treatment
      effects and no statistically significant heterogeneity were found when only
      trials were included that were "medically eligible" (involved patients with stage
      II disease and a pain-free walking distance of 50 to 200 m). In a similar
      sensitivity analysis of the absolute claudication distance, the two conditions
      resulting in a significant treatment effect and no significant heterogeneity were
      the inclusion of "medically eligible" trials and those with a shorter treatment
      duration (13 weeks or less). CONCLUSION: Pentoxifylline therapy may be
      efficacious in improving the walking capacity of patients with moderate
      intermittent claudication. However, properly conducted clinical trials are
      required to provide a true estimate of the benefit.

PMID- 8873634
TI  - The CMA Code of Ethics: more room for reflection.
AB  - Codes of ethics stand as a promise to society about the integrity of a profession
      in return for the power and authority given to that profession by society. The
      revised CMA Code of Ethics (see pages 1176A to 1176B) is timely and significant
      and should be applauded and supported by all physicians. It speaks clearly to
      competence, high standards of practice and communication, and the importance of
      informed patient choice. Nonetheless, the code provides no systematic
      justification for the principles it asserts. Although these principles are
      helpful tools, they are insufficient to resolve major ethical dilemmas. The code
      provides no means of ordering ethical priorities and fails to address issues such
      as peer review and conflict of interest. It is deafeningly silent on both
      abortion and euthanasia. In view of these limitations, the code must be seen as
      an important but unfinished reflection on the essence of being a good physician.

PMID- 8873635
TI  - Program descriptions: information for authors and peer reviewers.

PMID- 8873637
TI  - Bioethics for clinicians: 4. Voluntariness.
AB  - In the context of consent, "voluntariness" refers to a patient's right to make
      health care choices free of any undue influence. However, a patient's freedom to
      make choices can be compromised by internal factors such as pain and by external
      factors such as force, coercion and manipulation. In exceptional circumstances-
      for example, involuntary admission to hospital--patients may be denied their
      freedom of choice; in such circumstances the least restrictive means possible of
      managing the patient should always be preferred. Clinicians can minimize the
      impact of controlling factors on patients' decisions by promoting awareness of
      available choices, inviting questions and ensuring that decisions are based on an
      adequate, unbiased disclosure of the relevant information.

PMID- 8873636
TI  - Neuroimmune mechanisms in health and disease: 2. Disease.
AB  - In the second part of their article on the emerging field of neuroimmunology, the
      authors present an overview of the role of neuroimmune mechanisms in defence
      against infectious diseases and in immune disorders. During acute febrile
      illness, immune-derived cytokines initiate an acute phase response, which is
      characterized by fever, inactivity, fatigue, anorexia and catabolism. Profound
      neuroendocrine and metabolic changes take place: acute phase proteins are
      produced in the liver, bone marrow function and the metabolic activity of
      leukocytes are greatly increased, and specific immune reactivity is suppressed.
      Defects in regulatory processes, which are fundamental to immune disorders and
      inflammatory diseases, may lie in the immune system, the neuro endocrine system
      or both. Defects in the hypothalamus-pituitary-adrenal axis have been observed in
      autoimmune and rheumatic diseases, chronic inflammatory disease, chronic fatigue
      syndrome and fibromyalgia. Prolactin levels are often elevated in patients with
      systemic lupus erythematosus and other autoimmune diseases, whereas the
      bioactivity of prolactin is decreased in patients with rheumatoid arthritis.
      Levels of sex hormones and thyroid hormone are decreased during severe
      inflammatory disease. Defective neural regulation of inflammation likely plays a
      pathogenic role in allergy and asthma, in the symmetrical form of rheumatoid
      arthritis and in gastrointestinal inflammatory disease. A better understanding of
      neuroimmunoregulation holds the promise of new approaches to the treatment of
      immune and inflammatory diseases with the use of hormones, neurotransmitters,
      neuropeptides and drugs that modulate these newly recognized immune regulators.

PMID- 8873638
TI  - Preliminary conjoint statement on oral cholera vaccination.

PMID- 8873640
TI  - Revised Code of Ethics wins CMA approval.
AB  - Canadian physicians now operate under a revised Code of Ethics. In August General
      Council endorsed a revised code put forward by the CMA's Committee on Ethics. The
      endorsement brings 4 years' work to a positive conclusion.

PMID- 8873641
TI  - MDs' failure to use plain language can lead to the courtroom.
AB  - Two recent court cases in British Columbia reveal the importance of using plain,
      simple language to communicate with patients. This is particularly important
      because almost half of Canadians have low literacy levels. The CMA, which
      promotes the use of plain language in professional practice, is participating in
      the Canadian Public Health Association's National Literacy and Health Program.
      Resources are available to help physicians better serve patients.

PMID- 8873639
TI  - Clinical practice guidelines for the diagnosis and management of osteoporosis.
      Scientific Advisory Board, Osteoporosis Society of Canada.
AB  - OBJECTIVE: To recommend clinical practice guidelines for the assessment of people
      at risk for osteoporosis, and for effective diagnosis and management of the
      condition. OPTIONS: Screening and diagnostic methods: risk-factor assessment,
      clinical evaluation, measurement of bone mineral density, laboratory
      investigations. Prophylactic and corrective therapies: calcium and vitamin D
      nutritional supplementation, physical activity and fall-avoidance techniques,
      ovarian hormone therapy, bisphosphonate drugs, other drug therapies. Pain
      management medications and techniques. OUTCOMES: Prevention of loss of bone
      mineral density and fracture; increased bone mass; and improved quality of life.
      EVIDENCE: Epidemiologic and clinical studies and reports were examined, with
      emphasis on recent randomized controlled trials. Clinical practice in Canada and
      elsewhere was surveyed. Availability of treatment products and diagnostic
      equipment in Canada was considered. VALUES: Cost-effective methods and products
      that can be adopted across Canada were considered. A high value was given to
      accurate assessment of fracture risk and osteoporosis, and to increasing bone
      mineral density, reducing fractures and fracture risk and minimizing side effects
      of diagnosis and treatment. BENEFITS, HARMS AND COSTS: Proper diagnosis and
      management of osteoporosis minimize injury and disability, improve quality of
      life for patients and reduce costs to society. Rationally targeted methods of
      screening and diagnosis are safe and cost effective. Harmful side effects and
      costs of recommended therapies are minimal compared with the harms and costs of
      untreated osteoporosis. Alternative therapies provide a range of choices for
      physicians and patients. RECOMMENDATIONS: Population sets at high risk should be
      identified and then the diagnosis confirmed through bone densitometry. Dual
      energy x-ray absorptiometry is the preferred measurement technique. Radiography
      can be adjunct when indicated. Calcium and vitamin D nutritional supplementation
      should be at currently recommended levels. Patients should be counselled in fall
      avoidance techniques and exercises. Immobilization should be avoided. Guidelines
      for management of acute pain are listed. Ovarian hormone therapy is the therapy
      of choice for osteoporosis prevention and treatment in postmenopausal women.
      Bisphosphonates are an alternative therapy for women with established
      osteoporosis who cannot or prefer not to take ovarian hormone therapy.

PMID- 8873642
TI  - It's time for CMA to put the lid on privatization.
AB  - Family physician Cynthia Carver wasn't heartened by the CMA's "last-minute
      retreat" from a call to pursue privatization of health care. During its August
      annual meeting, the association not only supported a strong, publicly funded
      health care system but also passed a number of resolutions related to the private
      sector and the appropriate role for regulated private medical insurance in
      Canada. Carver proposes that the energy being expended on schemes to delist,
      privatize, define core services and design payment schemes should instead be
      applied to improving the existing system.

PMID- 8873643
TI  - In back alleys near Vancouver's AIDS conference, the disease was gaining ground.
AB  - There was much more to this summer's international AIDS conference in Vancouver
      than reports by researchers. Richard Cairney says the $15-million conference
      attracted a mix of activists, demonstrators, physicians and business
      representatives, and they coexisted somewhat uneasily.

PMID- 8873644
TI  - As hospitals shrink, consolidate or close, physicians are swept up in the
      turmoil.
AB  - Hospital closures are causing great uncertainty among Canadian physicians. As
      anatomical pathologist Vivien Frenkel told Nicole Baer, "the main thing now is
      that nobody knows what's going to happen, and that creates a lot of anxiety."
      Baer studies the impact hospital closures have had and are likely to have on
      physicians as the restructuring of Canada's health care system continues.

PMID- 8873645
TI  - Mandatory CPR training for students may improve cardiac-arrest survival rate, MDs
      say.
AB  - A mandatory cardiopulmonary resuscitation (CPR) program that started as a pilot
      project in Ottawa-area high schools is expanding to other Canadian schools.
      Besides CPR techniques, Grade 9 students are being taught about healthy
      lifestyles and how to recognize cardiac arrest. Emergency physician Justin
      Maloney, the program's principal architect, believes that in a decade this
      mandatory training will translate into increased bystander-initiated CPR and
      improved chances of survival for victims of cardiac arrest.

PMID- 8873646
TI  - Cost of health benefits becoming major business issue, conference told.
AB  - As governments attempt to off-load health care costs in an attempt to cut
      budgets, the bills are being passed to businesses that provide supplementary
      health care coverage. Business representatives attending a recent conference
      heard that employers experienced a 26% increase in the cost of providing
      supplementary health and dental benefits between 1990 and 1994.

PMID- 8873647
TI  - Code of Ethics of the Canadian Medical Association.

PMID- 8873648
TI  - Red Cross only positive result of horrifying 1859 bloodbath.
AB  - Haunted by the suffering and human devastation he witnessed after the 1859 Battle
      of Solferino in Italy, Swiss banker Henry Dunant wrote a book that galvanized
      European governments and resulted in the first international agreement that
      established rules for the conduct of war. The Geneva Convention also resulted in
      the formation of the Red Cross.

PMID- 8873649
TI  - What are you waiting for?

PMID- 8873650
TI  - The interventional cardiologist and the diabetic patient. Have we pushed the
      envelope too far or not far enough?

PMID- 8873651
TI  - Age and thrombolytic therapy.

PMID- 8873652
TI  - Estrogen therapy, atherosclerosis, and clinical cardiovascular events.

PMID- 8873653
TI  - Genetic polymorphism of methylenetetrahydrofolate reductase and myocardial
      infarction. A case-control study.
AB  - BACKGROUND: Elevated total plasma homocyst(e)ine (tHcy; the composite of
      homocysteine-derived moieties in their oxidized and reduced forms) levels are a
      risk factor for coronary heart disease, stroke, and venous thrombosis. tHcy
      plasma levels are influenced by folate, vitamins B6 and B12, as well as by
      hereditary factors. A point mutation (C677T) in the gene encoding
      methylenetetrahydrofolate reductase, an enzyme involved in homocysteine
      remethylation, has been reported to render the enzyme thermolabile and less
      active and has been associated with elevated tHcy in homozygous carriers (+/+
      genotype) as well as with increased risk of premature cardiovascular disease.
      METHODS AND RESULTS: We investigated whether this mutation influences risk for
      myocardial infarction (MI) and plasma levels of tHcy and whether this effect may
      be modified by dietary folate intake in 190 MI cases and 188 control subjects
      from the Boston Area Health Study. Genotype frequencies were 37.8% for -/-, 47.8%
      for +/-, and 14.4% for +/+ in the control group and 50.0% for -/-, 34.7% for +/-,
      and 15.3% for +/+ in the case group. The relative risk for MI associated with the
      +/+ genotype (compared with +/- and -/-) was 1.1 (95% CI, 0.6 to 1.9; P = .8).
      Stratification by folate intake values above and below the median did not
      significantly alter these results. Plasma tHcy levels were 9.9 +/- 2.7 mumol/L in
      -/- individuals, 10.6 +/- 3.8 mumol/L in +/- individuals, and 9.1 +/- 2.3 mumol/L
      in +/+ individuals (Ptrend = NS; determined in 68 cases and 59 control subjects).
      CONCLUSIONS: Our data show that homozygosity for the C677T mutation in this
      largely white, middle-class US population is not associated with increased risk
      for MI, irrespective of folate intake. This suggests that this mutation does not
      represent a useful marker for increased cardiovascular risk in this and in
      similar populations.

PMID- 8873654
TI  - Heart transplantation in Chagas' disease. 10 years after the initial experience.
AB  - BACKGROUND: Heart transplantation (HT) as a therapeutic option for end-stage
      chronic Chagas' heart disease (CCHD) is controversial. Reactivation of
      Trypanosoma cruzi infection and recurrence of the disease in the allograft are
      likely to occur. Furthermore, active myocarditis has been reported to predispose
      patients to an increased incidence and severity of rejection. METHODS AND
      RESULTS: We prospectively investigated the long-term follow-up of 10 patients
      with CCHD who underwent HT. Immunosuppression was based on cyclosporine A and
      azathioprine. T cruzi reactivation was prevented with benzonidazole. Besides
      allograft rejection surveillance, T cruzi infection was monitored through blood
      tests, myocardial biopsies, and serological tests. Over a mean follow-up period
      of 34 +/- 38 months (range, 73 to 124 months), 7 patients are alive and in NYHA
      functional class I. Life expectancy was 78% for the second year and 65% for 10
      years. Rejection was less frequent in chagasic than in age- and sex-matched
      control patients (mean +/- SD, 1.60 +/- 1.26 versus 5.70 +/- 1.89 episodes per
      patient, respectively; P = .0001); decreased severity of rejection was also
      observed (P = .006). T cruzi parasitemias detected on three occasions were
      successfully treated with benzonidazole. There were no signs of recurrence of the
      disease in the allograft. CONCLUSIONS: These results suggest an important role of
      HT in the treatment of CCHD. There was a low frequency of T cruzi infection
      reactivation and no signs of recurrence of the disease in the allograft. The
      surprisingly decreased rejection incidence and severity require further studies
      for elucidation.

PMID- 8873655
TI  - Coronary angioplasty in diabetic patients. The National Heart, Lung, and Blood
      Institute Percutaneous Transluminal Coronary Angioplasty Registry.
AB  - BACKGROUND: Patients with diabetes mellitus are at increased risk of
      cardiovascular disease. To date, the baseline status and subsequent outcomes of
      diabetic coronary angioplasty (percutaneous transluminal coronary angioplasty, or
      PTCA) patients with advanced atherosclerotic disease and with procedures
      performed across North America have not been well characterized. METHODS AND
      RESULTS: Data on baseline clinical and angiographic characteristics and short-
      and long-term outcomes of 281 diabetic and 1833 nondiabetic PTCA patients in the
      multicenter National Heart, Lung, and Blood Institute 1985-1986 PTCA Registry
      were analyzed. Diabetic patients were older, were more likely to be female, and
      had more comorbid baseline conditions, triplevessel disease, and atherosclerotic
      lesions. Angiographic success and completeness of revascularization did not
      differ significantly, yet diabetic patients experienced more in-hospital death
      (women) and nonfatal myocardial infarction. Nine-year mortality was twice as high
      in diabetic patients (35.9% versus 17.9%). Similarly, 9-year rates of nonfatal
      myocardial infarction (29.0% versus 18.5%), bypass surgery (36.7% versus 27.4%),
      and repeat PTCA (43.7% versus 36.5%) were higher in diabetics than in
      nondiabetics. In multivariate analysis, diabetes remained a significant predictor
      of decreased 9-year survival and other untoward events. CONCLUSIONS: Compared
      with nondiabetic PTCA patients, diabetic patients have more extensive and diffuse
      atherosclerotic disease. Despite similar probability of angiographic success,
      diabetic patients are more likely to suffer in-hospital death(women) and nonfatal
      myocardial infarction. Long-term survival and freedom from myocardial infarction
      and coronary revascularization is also reduced in diabetic PTCA patients. Whether
      PTCA or coronary bypass surgery is more suitable for these patients is currently
      under investigation.

PMID- 8873656
TI  - Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I
      trial. Global Utilization of Streptokinase and TPA for Occluded coronary arteries
      trial.
AB  - BACKGROUND: Elderly patients with acute myocardial infarction have much to gain
      from reperfusion with thrombolytic therapy but are also at increased risk of
      adverse events. We examined outcomes according to age of patients receiving
      thrombolysis in an international trial. METHODS AND RESULTS: Patients were
      randomized to streptokinase plus subcutaneous heparin, streptokinase plus
      intravenous heparin, accelerated tissue plasminogen activator (TPA) plus
      intravenous heparin, or streptokinase and TPA plus intravenous heparin. Clinical
      outcomes at 30 days (death, stroke, and nonfatal, disabling stroke) and 1-year
      mortality were summarized descriptively for patients aged < 65 (n = 24,708), 65
      to 74 (n = 11,201), 75 to 85 (n = 4625), and > 85 years (n = 412) and assessed as
      continuous functions of age. Older patients had a higher-risk profile with regard
      to baseline clinical and angiographic characteristics. Mortality at 30 days
      increased markedly with age (3.0%, 9.5%, 19.6%, and 30.3% in the four groups,
      respectively), as did stroke, cardiogenic shock, bleeding, and reinfarction.
      Combined death or disabling stroke occurred less often with accelerated TPA in
      all but the oldest patients, who showed a weak trend toward a lower incidence
      with streptokinase plus subcutaneous heparin: odds ratio 1.13; 95% confidence
      interval 0.6, 2.1. Similarly, accelerated TPA treatment resulted in lower 1-year
      mortality in all but the oldest patients (47% TPA versus 40.3% streptokinase).
      CONCLUSIONS: Lower mortality and greater net clinical benefit were seen with
      accelerated TPA in patients aged < or = 85 years. Because data are limited for
      patients aged > 85 years, the relative superiority of a given thrombolytic
      regimen cannot be determined. The interactions of stroke and mortality with newer
      thrombolytic strategies must be examined explicitly in older patients.

PMID- 8873657
TI  - Noninvasive assessment of myocardial viability by positron emission tomography
      with 11C acetate in patients with old myocardial infarction. Usefulness of low
      dose dobutamine infusion.
AB  - BACKGROUND: When patients with severely depressed left ventricular function are
      treated, it is crucial to know in advance how much functional recovery is
      expected from coronary revascularization. METHODS AND RESULTS: We compared the
      results of 11C acetate positron emission tomography (PET) with dobutamine
      infusion with changes in regional wall motion evaluated by left ventriculography
      in 28 patients with old Q-wave anterior myocardial infarctions. Dysfunctional but
      viable myocardium (group A, n = 13) was separated from nonviable myocardium
      (group B, n = 15) by echocardiographic assessments of regional wall motion before
      and after successful coronary revascularization. 11C acetate PET was performed to
      characterize normalized myocardial blood flow and oxidative metabolism (the
      clearance rate constant, k mono). While the baseline k monos of the infarct areas
      of the two groups were different with overlap, the responses to dobutamine
      infusion were directionally different. In addition, relative perfusion by 11C
      acetate PET could predict recovery of left ventricular function as well as or
      better than dobutamine 11C acetate kinetics. The extent of the increase in k
      monos of the infarct area with dobutamine infusion correlated well (P < .01) with
      the degree of the increase in the percentage of systolic segment shortening in
      the infarct area (left ventriculography) after coronary revascularization.
      CONCLUSIONS: 11C acetate PET with dobutamine infusion can predict not only the
      reversibility of dysfunctioning myocardium after coronary revascularization but
      also the extent of improvement of regional wall motion in patients with old Q
      wave infarction.

PMID- 8873658
TI  - Simultaneous coronary pressure and flow velocity measurements in humans.
      Feasibility, reproducibility, and hemodynamic dependence of coronary flow
      velocity reserve, hyperemic flow versus pressure slope index, and fractional flow
      reserve.
AB  - BACKGROUND: To assess coronary lesion severity in the catheterization laboratory,
      several guide wire-based methods have been proposed. The purpose of the present
      study was to compare the feasibility and the reproducibility of coronary flow
      velocity reserve (CFVR), instantaneous hyperemic diastolic velocity-pressure
      slope index (IHDVPS), and pressure-derived myocardial fractional flow reserve
      (FFRmyo). METHODS AND RESULTS: From distal coronary pressure and flow velocity
      signals (0.014-in guide wires), CFVR, IHDVPS, and FFRmyo were computed in 15
      stenoses (13 patients) under the four following pairs of conditions: (1) twice
      under baseline conditions; (2) during atrial pacing at 80 and 110 bpm; (3) before
      and during intravenous infusion of nitroprusside; and (4) before and during
      intravenous infusion of dobutamine. A total of 104 measurements were obtained.
      Both CFVR and FFRmyo could be calculated in all cases. IHDVPS could be calculated
      in only 79% of cases. The mean value of CFVR did not change between the two
      baseline measurements and during infusion of nitroprusside but decreased from
      1.85 +/- 0.41 to 1.66 +/- 0.45 (P < .05) during atrial pacing and from 1.90 +/-
      0.50 to 1.41 +/- 0.28 (P < .05) during dobutamine infusion. The mean values of
      IHDVPS and FFRmyo remained similar, whichever the changes in hemodynamic
      conditions. The coefficient of variation between two consecutive measurements was
      significantly lower for FFRmyo (4.2%) than for CFVR (17.7%) and for IHDVPS
      (24.7%). CONCLUSIONS: CFVR is easy to measure but sensitive to hemodynamic
      changes. IHDVPS can be measured only in < 80% of cases and is highly variable
      even without changes in hemodynamic conditions. FFRmyo is easy to measure and
      almost independent of hemodynamic changes.

PMID- 8873659
TI  - Preconditioning by transient myocardial ischemia confers protection against
      ischemia-induced ventricular arrhythmias in variant angina.
AB  - BACKGROUND: In experimental models, ischemic preconditioning of the heart
      protects against ischemic damage and ventricular arrhythmias during subsequent
      coronary occlusion. In this study, we investigated whether protection against
      ischemic suffering and ischemia-induced arrhythmias may occur after spontaneous
      transmural ischemia in humans. METHODS AND RESULTS: We performed 24-hour Holter
      monitoring in 10 patients with variant angina who developed complex ventricular
      arrhythmias (CVAs, more than five premature ventricular beats per minute or
      repetitive ventricular arrhythmias) during episodes of ST-segment elevation. A
      total of 150 episodes of ST-segment elevation were detected on Holter monitoring,
      21 (14%) of which showed CVAs. Episodes separated from the previous one by a time
      interval of < or = 30 minutes or by a time interval of > 30 minutes did not
      differ in either magnitude or duration of ST-segment elevation, but CVAs occurred
      more frequently in the second group (3% versus 29%, P < .0001). The time interval
      from the preceding ischemic episode was longer for the episodes with compared
      with those without CVAs (197 +/- 275 versus 57 +/- 87 minutes, P < .001), but
      these two groups of episodes also had similar severities and durations of ST
      segment elevation. Finally, when we analyzed 13 clusters of two to six ischemic
      episodes, CVAs were found much more frequently in the first (92%) than in the
      last (23%, P = .009) episode of the clusters, while ST-segment elevations were
      similar (2.1 +/- 1.6 versus 2.2 +/- 1.1 mm) and ischemia durations shorter in the
      first than in the last episode (3.9 +/- 3.6 versus 6.1 +/- 1.7 minutes, P = .03).
      CONCLUSIONS: Our data indicate that preconditioning by transient ischemia induces
      a significant protection against ischemia-induced CVAs in patients with variant
      angina. This beneficial effect was not related to a reduction in either severity
      or duration of ischemia, suggesting that arrhythmic protection was a direct
      consequence of preconditioning rather than an epiphenomenon of ischemic
      protection.

PMID- 8873661
TI  - Genetic regulation of hemodynamic variables during dynamic exercise. The MCV twin
      study.
AB  - BACKGROUND: Both resting and exercise levels of blood pressure in individuals
      have been used as predictors of adult hypertension. One possible mechanism
      underlying the relation between childhood resting and exercise blood pressure and
      future blood pressure is a set of genes expressed in childhood that persists to
      regulate adult blood pressure. METHODS AND RESULTS: To investigate the genetic
      relation of blood pressure and heart rate during both rest and exercise, we
      asked: (1) Are the genes that regulate resting hemodynamic variables the same
      genes that regulate these variables during exercise? (2) How much of the variance
      in exercise hemodynamic variables is genetic and how much is environmental? (3)
      Do the genetic and environmental influences on hemodynamic responses change with
      increasing levels of exercise? To determine how genetic and environmental effects
      expressed at rest influenced responses during dynamic exercise, a genetic
      analysis was conducted by fitting a series of models to the covariance matrices
      with the use of the LISREL VII program. CONCLUSIONS: We found that all the
      genetic effects expressed at the later stages of exercise can be explained by
      genetic effects expressed at rest and at the first stage of exercise. The
      environmental effects appear to be workload specific and include errors of
      measurement.

PMID- 8873660
TI  - No association of menopause and hormone replacement therapy with carotid artery
      intima-media thickness. Atherosclerosis Risk in Communities (ARIC) Study
      Investigators.
AB  - BACKGROUND: Cardiovascular disease is the major cause of death in older women.
      Information on the relation of menopause and hormone replacement therapy with
      carotid atherosclerosis is limited. METHODS AND RESULTS: We examined cross
      sectionally the association of menopausal status, years since last menstruation,
      and hormone replacement therapy status with carotid artery intima-media thickness
      as determined by B-mode ultrasound. Female participants (n = 5436) in the
      Atherosclerosis Risk in Communities Study without a history of symptomatic
      cardiovascular disease were included in the analyses. Menopause status in 45- to
      54-year-old women who had never used hormone replacement therapy was not strongly
      associated with carotid intima-media thickness (mean = 0.65 mm and 0.67 mm in
      premenopausal and postmenopausal women, respectively, adjusted for age, race,
      cigarette years of smoking, body mass index, sport index, systolic blood
      pressure, use of blood pressure medications, drinking status, diabetes, and
      education level). In postmenopausal women aged 55 to 64 years, women with < or =
      5 years since last menstruation had an adjusted average intima-media thickness
      (0.74 mm) comparable to those with > 5 years since last menstruation (0.75 mm) (P
      > .05). Although hormone replacement therapy use was associated with a more
      favorable lipid and hemostasis profile than nonuse, its use was not associated
      with intima-media thickness in postmenopausal women aged 55 to 64 years (adjusted
      average = 0.74 mm for current users of estrogen alone and approximately 0.75 mm
      each for current users of estrogen plus progestin, former users, and never
      users). CONCLUSIONS: The data suggest that the well-known associations of hormone
      replacement therapy with reductions in atherosclerotic cardiovascular disease may
      be attributable more to acute physiological effects, such as hemodynamic changes
      or reduced thrombosis, than to atherosclerosis itself.

PMID- 8873662
TI  - Reconstruction of brachial artery pressure from noninvasive finger pressure
      measurements.
AB  - BACKGROUND: Pulse wave distortions, mainly caused by reflections, and pressure
      gradients, caused by flow in the resistive vascular tree, may cause differences
      between finger and brachial artery pressures. These differences may limit the use
      of finger pressure measurements. We investigated whether brachial artery pressure
      waves could be reconstructed from finger pressure measurements by correcting for
      the pressure gradient in addition to correction for pulse wave distortion with a
      previously described filter. METHODS AND RESULTS: Finger artery pressure (with
      Finapres), intra-arterial brachial artery pressure (BAP), Riva-Rocci/ Korotkoff
      (RRK), oscillometric, and return-to-flow (RTF) measurements were simultaneously
      performed in 57 healthy elderly subjects and patients with vascular disease
      and/or hypertension. A generalized waveform filter was used to correct for pulse
      wave distortions. Correction equations for the pressure gradient, based on finger
      pressure, RRK, RTF, or oscillometric measurements, were obtained in 28 randomly
      selected subjects and tested in 29. Before reconstruction, Finapres
      underestimated mean and diastolic BAP (finger pressure minus BAP: systolic, -3.2
      +/- 16.9 mm Hg; mean, -13.0 +/- 10.5 mm Hg; diastolic, -8.4 +/- 9.0 mm Hg [mean
      +/- SD]). After filtering, reconstructed BAP waves were similar to actual BAP in
      shape but not in pressure level. Optimal correction for the pressure gradient
      with an equation based on RTF measurements reduced the pressure differences to
      meet American Association for the Advancement of Medical Instrumentation criteria
      (reconstructed finger pressure minus BAP: systolic, 3.7 +/- 7.0 mm Hg; mean, 0.7
      +/- 4.6 mm Hg; and diastolic, 1.0 +/- 4.9 mm Hg). CONCLUSIONS: BAP waves can be
      reconstructed from noninvasive finger pressure registrations when finger pressure
      waves are corrected for pulse wave distortion and individual pressure gradients.

PMID- 8873663
TI  - Precapillary servo control of blood pressure and postcapillary adjustment of flow
      to tissue metabolic status. A new paradigm for local perfusion regulation.
AB  - BACKGROUND: There are several shortcomings in current understanding of how the
      microvasculature maintains tissue homeostasis. Presently unresolved issues
      include (1) integration of the potentially conflicting needs for capillary
      perfusion and hydrostatic pressure regulation, (2) an understanding of signal
      transmission pathways for conveying information about tissue energetic status
      from undersupplied tissue sites to the arterioles, (3) accounting for the
      experimentally observed interrelations between precapillary and postcapillary
      resistances, and (4) an explanation of how precise local adjustment of perfusion
      to metabolic demands is achieved. METHODS AND RESULTS: A novel conceptualization
      of how local microvascular control mechanisms are coordinated is proposed,
      according to which blood flow is adjusted to the metabolic needs of the tissue by
      the venules. Arteriolar action is merely called on for controlling capillary
      pressure through myogenic response and shear stress-induced vasodilation. A
      mathematical model of this theory is introduced and evaluated using well
      established experimental data from the literature on regulating mechanisms of
      microvessel diameters exclusively. The model results demonstrate the suggested
      mode of microvascular operation to be functional and efficient under conditions
      present in vivo. Moreover, the predicted vascular responses are large enough to
      cover the entire range observed in exercising skeletal muscle during adjustment
      of perfusion to higher performance levels. CONCLUSIONS: Precapillary pressure
      regulation combined with postcapillary adjustment of perfusion to tissue
      metabolic status is suitable to resolve the above shortcomings in our current
      understanding of microvascular control. With mathematical modeling based on
      experimental data, this mode of microvascular operation is shown to be functional
      and effective in controlling muscle microcirculation.

PMID- 8873665
TI  - Creatine kinase system in failing and nonfailing human myocardium.
AB  - BACKGROUND: The creatine kinase (CK) reaction is important for rapid resynthesis
      of ATP when the heart increases its work. Studies defining the CK system in human
      failing and nonfailing myocardium are limited and in conflict. To resolve this
      conflict, we measured the activities of CK and its isoenzymes and the contents of
      creatine and CK-B in homogenates of human myocardium. METHODS AND RESULTS:
      Myocardium was sampled from 23 subjects who underwent heart transplant, 36
      subjects maintained in an intensive care unit before heart harvesting, 13
      accident victims, and 2 patients undergoing heart surgery. Since the
      characteristics of myocardium of potential organ donors differed from those of
      myocardium of accident victims, data are presented for three groups: failing,
      donor, and control. CK activity was 7.7 +/- 1.9 and 6.0 +/- 1.4 IU/mg protein in
      left (LV) and right (RV) ventricles of failing, 9.4 +/- 2.5 and 10.7 +/- 2 IU/mg
      protein in LV and RV of donor, and 11.6 +/- 2.4 IU/mg protein in LV of control
      hearts. CK-MM and the mitochondrial isoenzyme activities were lower in failing
      and donor LV, and CK-MB activity and CK-B content were higher in failing and
      donor hearts. Creatine contents were 64 +/- 25 and 56 +/- 18.6 nmol/mg protein in
      LV and RV of failing, 96 +/- 30 and 110 +/- 24 nmol/mg protein in LV and RV of
      donor, and 131 +/- 28 nmol/mg protein in LV of control hearts. CONCLUSIONS: In
      failing and nonfailing donor human myocardium, there is a combined decrease of CK
      activity and creatine that may impair the ability to deliver ATP to energy
      consuming systems.

PMID- 8873664
TI  - Evidence for the existence of a functional cardiac renin-angiotensin system in
      humans.
AB  - BACKGROUND: The presence of mRNA for the essential components of the renin
      angiotensin system (RAS) has been found in animal and human hearts. The present
      study was designed to provide evidence for the existence of a (functional)
      cardiac RAS. METHODS AND RESULTS: Twenty-four patients with atypical chest pain
      undergoing coronary angiography for diagnostic purposes were investigated. The
      cardiac production rate of angiotensins was estimated by measurement of the
      cardiac extraction of 125I-angiotensin I and 125I-angiotensin II associated with
      the determination of endogenous angiotensins in aortic and coronary sinus blood
      in normal, low, or high sodium diets. In a normal sodium diet, angiotensin I and
      II aorta-coronary sinus gradients were tendentially negative (-1.8 +/- 2.5 and 
      0.9 +/- 1.7 pg/mL, respectively), and the amounts of angiotensin I and II added
      by cardiac tissues were 6.5 +/- 3.1 and 2.7 +/- 1.3 pg/mL, respectively. The low
      sodium diet caused a significant increase in both plasma renin activity (PRA) and
      angiotensin I concentration in aortic but not in coronary sinus blood, resulting
      in a more negative aorta-coronary sinus gradient (-9.7 +/- 3.1 pg/mL, P < .01).
      Angiotensin formation by PRA in blood during transcardiac passage increased (P <
      .001), whereas angiotensin I formed by cardiac tissues decreased dramatically.
      Accordingly, in the low sodium diet, 125I-angiotensin II extraction did not
      change, the cardiac fractional conversion rate of 125I-angiotensin I to 125I
      angiotensin II notably decreased (P < .01), and angiotensin II formation by
      cardiac tissues was undetectable. The high sodium diet caused a decrease in PRA
      and no changes in cardiac extraction of radiolabeled angiotensins; conversely,
      angiotensin I formed by cardiac tissues, cardiac Ang I fractional conversion
      rate, and angiotensin II formed during transcardiac passage significantly (P <
      .01 for all) increased. CONCLUSIONS: These results provide evidence for the
      existence of a functional cardiac RAS independent of but related to the
      circulating RAS.

PMID- 8873666
TI  - Radiofrequency catheter ablation of right ventricular tachycardia late after
      repair of congenital heart defects.
AB  - BACKGROUND: Ventricular arrhythmias after repair of congenital heart defects are
      a common finding and possibly contribute to sudden death in these patients.
      Optimal antiarrhythmic management has not yet been defined. METHODS AND RESULTS:
      The study population consisted of 16 patients in whom ventricular arrhythmias
      occurred 11 to 42 years after complete surgical repair of congenital heart
      defects. Fifteen patients had a history of symptomatic sustained or nonsustained
      ventricular tachycardia, and 1 had frequent nonsustained ventricular tachycardia.
      The diagnostic mapping procedure to identify the origin of the arrhythmia
      included pace mapping during sinus rhythm, activation mapping, and pacing
      interventions during ventricular tachycardia. Catheter ablation was carried out
      by means of radiofrequency energy in the temperature-controlled mode. The follow
      up period was 6 to 33 months (mean, 16 months). A right ventricular origin of the
      tachycardia in the surgically corrected area could be determined in all patients.
      Catheter ablation was carried out without complications. Immediate
      noninducibility was achieved in 15 of the 16 patients. One patient in whom the
      tachycardia was again inducible at repeat stimulation 1 week later was
      successfully treated with amiodarone. Eleven patients were taken off
      antiarrhythmic drugs. During follow-up, none of them had a recurrence of the
      tachycardia that had been ablated. CONCLUSIONS: In patients with symptomatic or
      frequent ventricular tachycardia late after complete surgical repair of
      congenital heart defects, catheter ablation by means of radiofrequency energy is
      feasible and safe and thus might be taken into consideration for these patients.
      Short-term follow-up results are promising.

PMID- 8873667
TI  - Failure to detect connexin43 mutations in 38 cases of sporadic and familial
      heterotaxy.
AB  - BACKGROUND: Heterotaxy results from failure to establish normal left/right
      asymmetry during embryonic development. Typical manifestations include complex
      heart defects and malpositioning of abdominal organs. Missense base substitutions
      clustered in a 150-base pair region of the gap-junction gene connexin43 (cx43)
      have been implicated in the pathogenesis of heterotaxy. METHODS AND RESULTS: cx43
      was studied in 38 cases of sporadic and familial heterotaxy. A 400-base pair
      region containing the previously reported mutation sites was amplified and
      directly sequenced in 19 patients. Nineteen additional patients were tested for
      restriction fragments predicted by two of the previously reported missense
      substitutions. No difference from normal control subjects was detected in any of
      the patients. CONCLUSIONS: Randomly selected cases of heterotaxy are unlikely to
      be the result of mutations in cx43.

PMID- 8873668
TI  - The Asp9 Asn mutation in the lipoprotein lipase gene is associated with increased
      progression of coronary atherosclerosis. REGRESS Study Group, Interuniversity
      Cardiology Institute, Utrecht, The Netherlands. Regression Growth Evaluation
      Statin Study.
AB  - BACKGROUND: Many patients suffering from premature coronary artery disease report
      a family history for such events. A mutation in a particular gene, which confers
      susceptibility for atherosclerosis, will be found more frequently in individuals
      suffering from coronary atherosclerosis than in the general population. We have
      recently reported the identification of an Asp9 Asn substitution in the
      lipoprotein lipase (LPL) enzyme. We analyzed the impact of this mutation on the
      progression of coronary atherosclerosis and the effect of pravastatin in both
      carriers and noncarriers. METHODS AND RESULTS: All patients were enrolled in the
      quantitative coronary angiographic clinical trial REGRESS, which studied the
      impact of pravastatin therapy on coronary atherosclerosis. The Asp9 Asn mutation
      was identified in 38 of 819 (4.8%) patients. Carriers of the mutation more often
      had a positive family history of cardiovascular disease and lower HDL cholesterol
      levels than noncarriers. In the placebo group, carriers showed more progression
      of coronary atherosclerosis than noncarriers: mean reduction of the minimum
      obstruction diameter of -0.25 mm versus -0.12 mm (P = .029) and increase of
      percentage diameter stenosis of 6.4% versus 1.4% (P = .004). Moreover, the
      adjusted relative risk for a clinical event for carriers was calculated at 2.16
      (95% CI, 1.09 to 4.29; P = .027). Although the lipid-lowering effect of
      pravastatin was attenuated in carriers, it appeared that these patients showed a
      response similar to noncarriers in terms of less progression of atherosclerosis
      and event-free survival. CONCLUSIONS: This study shows that heterozygosity for a
      mutation in the LPL gene, which causes only subtle changes in fasting plasma
      lipids, may promote the progression of coronary atherosclerosis and diminish
      clinical event-free survival.

PMID- 8873670
TI  - Reduction in myocardial infarct size by basic fibroblast growth factor after
      temporary coronary occlusion in a canine model.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) has been shown to reduce
      infarct size in canine acute myocardial infarction; however, the mechanism of
      tissue salvage remains uncertain. We evaluated the effect of bFGF on infarct size
      in a model of acute infarction in which coronary occlusion was followed by
      prolonged reperfusion and sought to determine whether reperfusion attenuates the
      stimulus for myocardial neovascularization. METHODS AND RESULTS: Anesthetized
      dogs undergoing 4-hour balloon occlusion of the left anterior descending coronary
      artery were treated with intracoronary bFGF (n = 8) or vehicle (n = 6). Ten
      microgram doses of bFGF were administered 10 minutes after occlusion and again
      immediately before reperfusion. Left ventriculograms were obtained before
      occlusion, after reperfusion, and preceding euthanasia on day 7. Infarct size,
      expressed as a percentage of the area at risk, was reduced in bFGF-treated dogs
      (13.7 +/- 2.1% versus 28 +/- 3.4%; P = .002). Changes in left ventricular
      ejection fraction, capillary density, and cellular proliferation-assessed
      immunohistochemically with factor VIII and proliferating cell nuclear antigen
      antibodies-were similar in both groups. To assess coronary vasomotor responses to
      bFGF, a separate hemodynamic study was performed in five anesthetized nonischemic
      dogs in which incremental bFGF doses up to 100 micrograms induced no vasodilator
      response. CONCLUSIONS: Treatment with bFGF was associated with a reduction in
      infarct size without hemodynamic effects or evidence of neovascularization. These
      data suggest that bFGF mediates myocardial salvage independently of angiogenesis
      and that reperfusion after infarction may attenuate the stimulus for
      neovascularization.

PMID- 8873669
TI  - Inhaled nitric oxide increases coronary artery patency after thrombolysis.
AB  - BACKGROUND: Nitric oxide (NO) and nitrosovasodilators that release NO inhibit
      platelet aggregation. The antithrombotic effect of intravenously infused
      nitrosovasodilators is usually accompanied by systemic vasodilation. Inhaled NO
      is a pulmonary vasodilator that does not produce systemic hemodynamic effects.
      This study examines the antithrombotic effect of inhaled NO in a canine model of
      platelet-mediated coronary artery reocclusion after thrombolysis. METHODS AND
      RESULTS: In 25 anesthetized dogs, a segment of the left anterior descending
      coronary artery was traumatized and a high-grade stenosis created. Thrombus was
      injected at this site, and tissue plasminogen activator was administered,
      producing cyclic flow variations (CFVs) in 24 of 25 dogs. CFV frequency was
      unchanged in dogs not breathing NO but decreased by 35 +/- 9% (P < .05) and 53 +/
      7% (P < .01) while dogs breathed 20 and 80 parts per million (ppm) NO,
      respectively. The coronary artery patency ratio (fraction of time during which
      the coronary artery was patent; CAPR) was unchanged in dogs not treated with NO
      but increased from 51 +/- 7% to 64 +/- 8% while breathing 20 ppm NO (P < .01) and
      from 49 +/- 3% to 75 +/- 7% while breathing 80 ppm NO (P < .01). The increased
      CAPR during 80 ppm NO administration persisted during a 45-minute posttreatment
      period (70 +/- 7%, P < .05 versus baseline). NO inhalation did not change
      systemic hemodynamics. In a pharmacological model of coronary vasoconstriction,
      inhaled NO did not reverse the effect of the thromboxane A2 agonist U-46619. In
      vitro ADP-induced platelet aggregation was inhibited by NO gas. CONCLUSIONS:
      Inhaled NO at concentrations of 20 and 80 ppm increases coronary patency and
      decreases CFV frequency in a canine model of platelet-mediated coronary
      reocclusion after thrombolysis without producing systemic hemodynamic effects.

PMID- 8873671
TI  - Importance of pressure recovery for the assessment of aortic stenosis by Doppler
      ultrasound. Role of aortic size, aortic valve area, and direction of the stenotic
      jet in vitro.
AB  - BACKGROUND: Pressure recovery has been shown to occur distal to aortic stenoses
      in experimental and clinical studies. However, its clinical relevance in this
      setting has not yet been evaluated. METHODS AND RESULTS: To address the
      hypothesis that pressure recovery can cause significant differences between
      Doppler and catheter gradients in aortic stenosis and to examine the effects of
      aortic size, aortic valve area, and direction of the stenotic jet on these
      differences, stenoses with valve areas from 0.5 to 1.25 cm2 and aortic diameters
      from 1.8 to 5.0 cm were studied in a pulsatile flow model. Jets entered the aorta
      centrally or eccentrically with angles of 15 degrees, 30 degrees, or 45 degrees.
      Overall, good correlation was found between Doppler and catheter gradients.
      However, when the various combinations of orifices and aortas were analyzed
      separately, slopes varied from 1.0 to 1.86, and the Doppler-catheter gradient
      differences ranged from -2 (small valve area with a large aorta) to 66 mm Hg (80%
      overestimation by Doppler echocardiography) when the stenosis was moderate and
      the aorta was small. Mild eccentricity of the jet did not significantly alter the
      results. However, overestimation by Doppler decreased with increasing jet
      eccentricity. Finally, differences between Doppler and catheter gradients could
      be predicted by estimating pressure recovery from Doppler measurements.
      CONCLUSIONS: Significant pressure recovery can occur in aortic stenosis and can
      cause differences between Doppler and catheter gradients. These differences may
      reach clinical relevance, particularly when the stenosis is moderate and the
      aorta is small and can be predicted from Doppler measurements.

PMID- 8873672
TI  - Inhibition of tissue angiotensin-converting enzyme with quinapril reduces hypoxic
      pulmonary hypertension and pulmonary vascular remodeling.
AB  - BACKGROUND: Angiotensin II may contribute to hypoxic pulmonary hypertension via
      its vasoconstrictor and growth-stimulatory effects on vascular smooth muscle
      cells (VSMCs). Therefore, the use of ACE inhibitors might reduce hypoxic
      pulmonary hypertension by decreasing pulmonary vasomotor tone or vascular
      remodeling. METHODS AND RESULTS: Pulmonary hemodynamics and vascular remodeling
      were compared in chronically hypoxic (FIO2 = 0.10) rats treated with 0, 1, and 10
      mg.kg-1.d-1 quinapril, a potent tissue ACE inhibitor, both during and after the
      development of pulmonary hypertension. Quinapril reduced the development of
      pulmonary hypertension after 12 days of hypoxia from 26 +/- 1 to 19 +/- 1 mm Hg
      (P < .05). When started in established pulmonary hypertension, quinapril reduced
      pulmonary artery pressure and total pulmonary resistance index from 29 +/- 1 to
      25 +/- 1 mm Hg and from 0.136 +/- 0.01 to 0.101 +/- 0.005 mm Hg .mL-1.min-1 per
      kg, respectively (P < .05). Chronically hypoxic rats showed a small pulmonary
      vasoconstrictor response that was not affected by quinapril. In contrast, percent
      medial thickness in alveolar duct blood vessels was reduced by quinapril
      treatment both in developing and in established pulmonary hypertension (10.0 +/-
      0.2% versus 8.9 +/- 0.1% [P < .05] and 11.2 +/- 0.2% versus 9.1 +/- 0.2% [P <
      .05], respectively). 5'-Bromo-deoxyuridine-positive VSMCs were detected in 56 +/-
      3% of hypoxic control pulmonary resistance vessels versus 41 +/- 3% of vessels
      after quinapril treatment (P < .05). CONCLUSIONS: Pulmonary ACE and angiotensin
      II contribute to the development and maintenance of hypoxic pulmonary
      hypertension in rats. ACE inhibition with quinapril reduces the development of
      hypoxic pulmonary hypertension and in part reverses established pulmonary
      hypertension, most likely via inhibition of pulmonary VSMC proliferation and/or
      growth.

PMID- 8873673
TI  - Inducible nitric oxide synthase and the regulation of central vessel caliber in
      the fetal rat.
AB  - BACKGROUND: The purpose of this study was to evaluate the possibility that
      inducible nitric oxide synthase (iNOS) regulates the fetal circulation. METHODS
      AND RESULTS: Positive evidence for iNOS gene expression was noted in heart
      central vessels and placenta of untreated rat fetuses. Rats in the last week of
      pregnancy were treated for 5 days with L-NG-(1-Iminoethyl)lysine (L-NIL), a
      selective inhibitor of iNOS, at 1, 10, and 100 micrograms/mL in the drinking
      water. To raise NO levels, lipopolysaccharide (LPS) 30 micrograms/kg was given by
      intraperitoneal injection, and sodium nitroprusside (SNP) was placed in mini
      osmotic pumps to deliver 10 micrograms/kg per minute. Control animals were
      undisturbed. On day 21 of gestation, dams were anesthetized and fetuses were
      delivered by cesarean section and rapidly frozen in isopentane chilled in liquid
      nitrogen. Frozen sections (10 microns) were used to reconstruct a computer
      generated three-dimensional image of the great vessels and ductus arteriosus.
      Significant constriction of the great vessels and ductus arteriosus was observed
      with L-NIL, whereas both LPS and SNP dilated these vessels. The vasorelaxant
      effect of LPS was blocked by L-NIL. NO release from placental explants was 633 +/
      41 nmol/L under basal conditions, increasing to 4.0 +/- 0.4 mumol/L with LPS
      administration, although placental iNOS message and protein levels were
      unchanged. CONCLUSIONS: We suggest that nitric oxide, generated by iNOS, plays a
      significant role in control of major vessel and ductus arteriosus caliber in the
      rat fetus. In regard to the nitrergic regulation of the circulation, the fetus is
      clearly different from the adult.

PMID- 8873674
TI  - Relative role of alkalosis and sodium ions in reversal of class I antiarrhythmic
      drug-induced sodium channel blockade by sodium bicarbonate.
AB  - BACKGROUND: Hypertonic sodium salts are used to treat sodium channel-blocking
      drug cardiotoxicity. The relative roles of alkalinization and increased sodium
      concentration ([Na+]o) for various drugs are incompletely known. METHODS AND
      RESULTS: The effects of four class I drugs on action potential characteristics of
      canine Purkinje fibers at equieffective concentrations (disopyramide 30 mumol/L,
      mexiletine 80 mumol/L, flecainide 7 mumol/L, imipramine 5 mumol/L) were studied
      in the presence of normal Tyrode solution and one altered solution (increased
      [Na+]o, increased bicarbonate concentration, or both) in each experiment.
      Combined increases in sodium and bicarbonate concentration significantly reduced
      the depressant effects of flecainide, imipramine, and mexiletine on phase 0
      upstroke (Vmax) but did not alter the effects of disopyramide. The effects of
      sodium bicarbonate were entirely due to alkalinization in the case of imipramine,
      but both alkalinization and increased [Na+]o contributed to the interaction with
      flecainide and mexiletine. The reversal of Vmax depression by increased [Na+]o
      and pH was due in part to hyperpolarization. In addition, alkalosis directly
      reversed the hyperpolarizing shift in Vmax inactivation caused by flecainide and
      imipramine without altering the shift caused by disopyramide and mexiletine.
      CONCLUSIONS: Increases in sodium bicarbonate concentration reverse the effects of
      class I antiarrhythmic drugs to a varying extent, with drug-specific
      contributions of the sodium and bicarbonate moiety. The molecular basis for this
      drug specificity remains to be elucidated, but it has important potential
      implications for the use of hypertonic sodium salts to treat cardiotoxicity
      caused by sodium channel-blocking drugs.

PMID- 8873675
TI  - Mechanism of spontaneous termination of functional reentry in isolated canine
      right atrium. Evidence for the presence of an excitable but nonexcited core.
AB  - BACKGROUND: According to the spiral wave hypothesis of reentry, the core of
      functional reentry remains excitable but not excited. We sought to determine
      whether the core remains excitable and whether excitation of the core by an
      outside wave front leads to termination of the reentry in the atrium. METHODS AND
      RESULTS: In nine isolated canine right endocardial atrial tissues (3.8 by 3.2 cm
      wide), reentry was induced by a premature point stimulus (S2). The isochronal
      activation maps and dynamics of the activation patterns were visualized with the
      use of 509 bipolar electrodes (1.6-mm resolution). The S2 applied after 8 regular
      beats induced reentry with a mean cycle length of 162 +/- 20 ms (15 episodes).
      Reentry had a large excitable gap (93 +/- 26 ms) as determined by early capture
      with twice the level of threshold stimuli. The central area (core) around which
      the wave fronts rotated had a mean surface area of 12 +/- 3 mm2. The electrograms
      located in the core of the reentry registered no or very low amplitude
      potentials. In 13 of 15 episodes, reentry terminated when an outside new wave
      front merged with the original wave front and excited the core. Core excitation
      caused disruption of the original wave front, and the newly formed wave front(s)
      vanished at the tissue border within 77 +/- 18 ms. In 2 episodes, reentry
      terminated abruptly when an outside new wave front propagating in a direction
      opposite to the reentrant wave front collided with the leading edge of the
      reentrant wave front. CONCLUSIONS: Functional reentry in the atrium is compatible
      with a spiral wave of excitation with an excitable but nonexcited core and a
      large excitable gap. Reentry may be terminated either by direct excitation of the
      core that displaces the wave front to the tissue border or by collision with an
      outside new wave front.

PMID- 8873676
TI  - Reduced arrhythmogenicity of biphasic versus monophasic T-wave shocks.
      Implications for defibrillation efficacy.
AB  - BACKGROUND: Biphasic waveforms defibrillate more effectively than monophasic
      waveforms; however, the mechanism remains unknown. The "upper-limit-of
      vulnerability" hypothesis of defibrillation suggests that unsuccessful
      defibrillation is due to reinduction of ventricular fibrillation (VF). Thus, VF
      induction mechanisms may be important for the understanding of defibrillation
      mechanisms. We therefore compared myocardial VF vulnerability for monophasic
      versus biphasic shocks. METHODS AND RESULTS: In 10 Langendorff-perfused rabbit
      hearts, monophasic and biphasic T-wave shocks were randomly administered over a
      wide range of shock coupling intervals and shock strengths, and the two
      dimensional coordinates within which VF was induced were used to calculate the
      area of vulnerability (AOV) for both shock waveforms. The arrhythmic response to
      biphasic shocks differed from that to monophasic shocks in three distinct ways:
      (1) the AOV was smaller (8.9 +/- 4.2 versus 13.9 +/- 6.0 area units, P < .02),
      (2) the transition zone between VF-inducing and nonarrhythmogenic shocks was
      narrower (14.7 +/- 4.8 versus 29.9 +/- 6.4 area units, P < .001), and (3) the
      entire AOV shifted toward longer coupling intervals (by 11.0 +/- 8.8 ms at the
      left border [P < .005] and 6.0 +/- 5.2 ms at the right border [P = .005] of the
      AOV). CONCLUSIONS: Biphasic shocks encounter a smaller AOV than monophasic
      shocks, a narrower transition zone from VF to no arrhythmia induction, and a
      lesser effectiveness in inducing VF at short coupling intervals. In keeping with
      the upper-limit-of-vulnerability hypothesis, these waveform-dependent differences
      in VF inducibility might help explain the lower defibrillation threshold for
      biphasic shocks.

PMID- 8873677
TI  - Regional differences in electrophysiological properties of epicardium,
      midmyocardium, and endocardium. In vitro and in vivo correlations.
AB  - BACKGROUND: Microelectrode studies have described a population of cells within
      the midmyocardium (M cells) displaying a steep rate dependence of action
      potential duration (APD) and high Vmax compared with endocardial (Endo) and
      epicardial (Epi) cells. METHODS AND RESULTS: We studied repolarization in
      different myocardial layers in vitro and in situ. In addition to confirming the
      results of earlier studies, we found that after abrupt lengthening of the cycle
      length (CL), APDs in M cells reached a new steady state faster than in Epi or
      Endo cells: the time to achieve 90% of the difference in APD (t90) was 13.3 +/-
      0.7 minutes in Endo cells, 12.8 +/- 1.1 minutes in Epi cells, and 2.6 +/- 0.4
      minutes in M cells (P < .05 compared with Epi or Endo) when CL changed from 400
      to 1000 ms. In situ, we registered activation-recovery intervals (ARIs) in
      bipolar electrograms obtained from different myocardial layers in conditions of
      AV block and His-bundle pacing. At all CLs from 300 to 2000 ms, ARIs were equal
      in all myocardial layers from Epi to Endo cells. Steady-state ARIs coincided with
      APD of M cells registered in vitro in the physiological range of CL from 300 to
      700 ms. When CL was changed from 300 to 1000 ms, the ARI followed the rapid time
      course typical of M cells (t90 = 2.6 +/- 0.5, 2.2 +/- 0.4, 2.5 +/- 0.4, 2.6 +/-
      0.5, and 2.3 +/- 0.4 minutes for Epi; 3-, 5-, and 7-mm sub-Epi; and Endo cells,
      respectively). CONCLUSIONS: In contrast to in vitro results, there is no
      significant difference in repolarization among myocardial layers in the intact
      normal canine heart.

PMID- 8873679
TI  - Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future
      directions. The SADS Foundation Task Force on LQTS.
AB  - The congenital long-QT syndrome (LQTS) is characterized by prolonged QT
      intervals, QT interval lability, and polymorphic ventricular tachycardia. The
      manifestations of the disease vary, with a high incidence of sudden death in some
      affected families but not in others. Mutations causing LQTS have been identified
      in three genes, each encoding a cardiac ion channel. In families linked to
      chromosome 3, mutations in SCN5A, the gene encoding the human cardiac sodium
      channel, cause the disease, Mutations in the human ether-a-go-go-related gene
      (HERG), which encodes a delayed-rectifier potassium channel, cause the disease in
      families linked to chromosome 7. Among affected individuals in families linked to
      chromosome 11, mutations have been identified in KVLQT1, a newly cloned gene that
      appears to encode a potassium channel. The SCN5A mutations result in defective
      sodium channel inactivation, whereas HERG mutations result in decreased outward
      potassium current. Either mutation would decrease net outward current during
      repolarization and would thereby account for prolonged QT intervals on the
      surface ECG. Preliminary data suggest that the clinical presentation in LQTS may
      be determined in part by the gene affected and possibly even by the specific
      mutation. The identification of disease genes in LQTS not only represents a major
      milestone in understanding the mechanisms underlying this disease but also
      presents new opportunities for combined research at the molecular, cellular, and
      clinical levels to understand issues such as adrenergic regulation of cardiac
      electrophysiology and mechanisms of susceptibility to arrhythmias in LQTS and
      other settings.

PMID- 8873678
TI  - Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous
      anastomotic intimal hyperplasia in the arteriovenous graft.
AB  - BACKGROUND: The plant cytotoxin saporin (SAP) is a potent ribosome-inactivating
      protein. When conjugated to basic fibroblast growth factor (FGF2), it selectively
      kills proliferating cells that have upregulated FGF receptors. In this study, we
      evaluated the effect of the recombinant chimeric mitotoxin rFGF2-SAP on venous
      anastomotic intimal hyperplasia, a major cause of failure of arteriovenous (AV)
      grafts. METHODS AND RESULTS: Recently designed expanded polytet-rafluoroethylene
      based local infusion devices were implanted bilaterally as femoral AV conduits in
      six dogs. The venous anastomoses were the sites of continuous delivery of rFGF2
      SAP (2.7 micrograms.kg-1.d-1) to one side and vehicle (4.6 microL.kg-1.d-1) as
      control to the contralateral side for 14 days. All animals survived, and all
      grafts were patent. Liver enzyme levels and histological analyses of liver,
      kidneys, and brain were normal, indicating the absence of systemic toxicity.
      Morphometric measurements and measurements of cell proliferation by
      bromodeoxyuridine index analysis were performed at both arterial and venous
      anastomoses. There were no significant differences between the treated grafts and
      the control grafts in intimal hyperplasia and intimal cell proliferation at the
      arterial anastomoses. In contrast, rFGF2-SAP reduced intimal thickness by 32%,
      intimal area by 40%, and cell proliferation index by 33% at the treated venous
      anastomoses compared with the control venous anastomoses (P < .05). CONCLUSIONS:
      These data demonstrate that local infusion of rFGF2-SAP significantly reduces
      venous anastomotic intimal hyperplasia and cell proliferation without systemic
      toxicity. This study suggests a new strategy for reducing intimal hyperplasia by
      the selective killing of proliferating smooth muscle cells with a potent chimeric
      mitotoxin through a novel local infusion device.

PMID- 8873680
TI  - Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley
      White Lecture 1995.

PMID- 8873681
TI  - Clinical approach to genetic cardiomyopathy in children.
AB  - BACKGROUND: Cardiomyopathy (CM) remains one of the leading cardiac causes of
      death in children, although in the majority of cases, the cause is unknown. To
      have an impact on morbidity and mortality, attention must shift to etiology
      specific treatments. The diagnostic evaluation of children with CM of genetic
      origin is complicated by the large number of rare genetic causes, the broad range
      of clinical presentations, and the array of specialized diagnostic tests and
      biochemical assays. METHODS AND RESULTS: We present a multidisciplinary
      diagnostic approach to pediatric CM of genetic etiology. We specify criteria for
      abnormal left ventricular systolic performance and structure that suggest CM
      based on established normal echocardiographic measurements and list other
      indications to consider an evaluation for CM. We provide a differential diagnosis
      of genetic conditions associated with CM, classified as inborn errors of
      metabolism, malformation syndromes, neuromuscular diseases, and familial isolated
      CM disorders. A diagnostic strategy is offered that is based on the clinical
      presentation: biochemical abnormalities, encephalopathy, dysmorphic features or
      multiple malformations, neuromuscular disease, apparently isolated CM, and
      pathological specimen findings. Adjunctive treatment measures are recommended for
      severely ill patients in whom a metabolic cause of CM is suspected. A protocol is
      provided for the evaluation of moribund patients. CONCLUSIONS: In summary, we
      hope to assist pediatric cardiologists and other subspecialists in the evaluation
      of children with CM for a possible genetic cause using a presentation-based
      approach. This should increase the percentage of children with CM for whom a
      diagnosis can be established, with important implications for treatment,
      prognosis, and genetic counseling.

PMID- 8873682
TI  - Images in cardiovascular medicine. Fungal mass on the tricuspid valve.

PMID- 8873683
TI  - The challenge of in-hospital medication use: an opportunity for clinical
      pharmacology.

PMID- 8873684
TI  - Reserpine: a tragic victim of myths, marketing, and fashionable prescribing.

PMID- 8873685
TI  - Determination of cytochrome P450 3A4/5 activity in vivo with dextromethorphan N
      demethylation.
AB  - Dextromethorphan is used widely in vivo to phenotype the polymorphically
      expressed cytochrome P450 (CYP) 2D6. Dextromethorphan is N-demethylated in vitro
      to 3-methoxymorphinan by human CYP3A4/5. We examined whether the
      dextromethorphan/3-methoxymorphinan urinary metabolic ratio (MR) could be used as
      an in vivo probe of CYP3A. Urinary excretion of 3-methoxymorphinan was excretion
      rate-limited in extensive metabolizers of CYP2D6, which necessitated a longer
      urine collection, 0 to 72 hours, to obtain true MR values for CYP3A. The urine
      excretion of dextromethorphan and 3-methoxymorphinan was delayed in poor
      metabolizers of CYP2D6 but appeared to be formation rate-limited. The delayed
      excretion in poor metabolizers necessitated longer urine collection intervals, 0
      to 11 days, to estimate the true CYP3A MR and 0 to 8 days to estimate the true
      CYP2D6 MR. However, a 72-hour collection in poor metabolizers was used as an
      index of the true dextromethorphan/3-methoxymorphinan MR. Rifampin (300 mg b.i.d.
      for 7 days) significantly reduced the 0- to 72-hour dextromethorphan/3
      methoxymorphinan MR consistent with an 830% (+/- 1808%) induction of CYP3A
      activity (n = 8), whereas erythromycin (250 mg q.i.d. for 7 days) significantly
      increased the dextromethorphan/3-methoxymorphinan MR, corresponding to a 34% +/-
      44% inhibition of activity (n = 7) in extensive metabolizers and poor
      metabolizers. The changes in CYP3A activity were independent of CYP2D6 phenotype
      and were also observed after 24- and 48-hour urine collections in extensive
      metabolizers and poor metabolizers. In addition, MRs reflecting CYP2D6 and CYP3A
      were not significantly correlated. We conclude that the commonly used antitussive
      dextromethorphan can be used as an in vivo marker of CYP3A and CYP2D6 activity.

PMID- 8873686
TI  - Chronopharmacokinetics of nicotine.
AB  - RATIONALE: For high-clearance drugs such as nicotine, hemodynamic changes
      throughout the day may be expected to influence the rate of metabolism. MATERIAL
      AND METHODS: To assess the effects of meals and diurnal rhythms on nicotine
      clearance, an intravenous infusion of nicotine bitartrate was administered for 48
      hours to 11 subjects. Two models to determine nicotine clearance variation
      throughout the day are described. Both models were used to estimate the mean
      effect of meal and diurnal rhythms on nicotine clearance and individual
      parameters that were regressed against baseline covariates. Clearance was modeled
      as a function of time [CL(t)] and split it in three components: a (constant)
      baseline value (theta 1), its circadian (diurnal) variation, and the effect of
      meal: CL(t) = [theta 1 + circadian(t)] [1 + meal(t)]. A two-compartmental (time
      variant) model incorporating CL(t) was then fitted to the data providing
      estimates of CL(t) conditional on literature values of the time-invariant
      parameters (volume of distribution and intercompartmental clearances). RESULTS:
      The estimated circadian(t) showed a maximum at approximately 11 AM and a flat
      minimum from 6 PM to 3 AM; the estimated meal(t) showed a sharp increase up to 1
      hour (after the meal), at which point clearance is increased 42%, and a slower
      decrease thereafter, returning to baseline (zero) after 2.8 hours. Individual
      estimates of baseline clearance are found to have a linear relationship with body
      weight. No other covariate, sex in particular, effect could be found.

PMID- 8873688
TI  - Pharmacokinetics of bumetanide in critically ill infants.
AB  - OBJECTIVE: Define the pharmacokinetics of bumetanide after single intravenous
      doses in volume-overloaded critically ill infants. METHODS: A prospective, open
      label study was carried out in a group of 58 infants aged 0 to 6 months who
      required diuretic therapy. Each patient received a single dose of intravenous
      bumetanide. Doses selected in sequential order ranged from 0.005 to 0.10 mg/kg.
      Hematologic and serum chemistry studies were performed before and at 6 and 24
      hours after bumetanide administration. Determinations of urine volume and
      chemistries were performed before (collected from -2 to -4 hours to time 0) and
      at 1, 2, 3, 4, 6, and 12 hours after bumetanide dosing. Serum samples collected
      at time 0 and at 5, 15, 30, 60, 120, 180, 240, 360, and 480 minutes and urine
      collected at time 0 and at 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6 to 12
      hours were analyzed for bumetanide concentration. Data were evaluated by standard
      noncompartmental pharmacokinetic techniques. RESULTS: Peak serum bumetanide
      concentrations occurred at 5 minutes after bumetanide administration. Area under
      the curve and peak serum bumetanide concentrations showed linear increases over
      the twentyfold dose range; whereas beta volume of distribution, volume of
      distribution at steady state, clearance, renal clearance, half-life, and mean
      residence time values were independent of dose. Peak urinary excretion rates of
      bumetanide increased linearly with increasing doses. The mean percent of
      bumetanide recovered in the urine from 0 to 12 hours was 40% +/- 15% of the
      administered dose. CONCLUSIONS: Distribution and elimination kinetics of
      bumetanide were similar in all patients. Elimination kinetics were first order
      over the dose range of 0.005 to 0.10 mg/kg. Pharmacokinetic parameter estimates
      (beta volume of distribution, volume of distribution at steady state, clearance,
      renal clearance, half-life, and mean residence time) were independent of the dose
      of bumetanide administered. Single doses of bumetanide up to 0.10 mg/kg appear to
      be well tolerated in acutely ill volume-overloaded infants aged 0 to 6 months.

PMID- 8873687
TI  - Differences between white subjects and Chinese subjects in the in vivo inhibition
      of cytochrome P450s 2C19, 2D6, and 3A by omeprazole.
AB  - OBJECTIVES: To determine the effects of omeprazole on indexes of CYP2D6, CYP2C19
      and 3A in vivo activity and to compare these in white subjects and Chinese
      subjects. METHODS: Omeprazole, 40 mg/day, or placebo were administered in a
      double-blind crossover study for 3 weeks to eight healthy white and seven Chinese
      male extensive metabolizers of mephenytoin and debrisoquin. Debrisoquin (10 mg),
      dapsone (100 mg), and mephenytoin (100 mg) were given 1 week before
      administration, on the last day of administration, and 3 weeks after
      administration, and urine was collected over 8 hours. Phenotypic trait values
      were obtained from the urinary recoveries of the probe drugs or their
      metabolites. RESULTS: In the white subjects, omeprazole significantly inhibited
      CYP2C19-mediated S-mephenytoin metabolism as indicated by decreases in the
      urinary R/S enantiomeric ratio (63% +/- 13%; p < 0.02; mean +/- SD) and the
      excretion of 4'-hydroxymephenytoin (39% +/- 13%; p < 0.001). Similar but smaller
      changes were also noted in Chinese subjects, 22% +/- 25% (p = 0.08) and 29% +/-
      13% (p < 0.002), respectively. The interracial differences in the extent of
      inhibition of metabolism were statistically significant (p < 0.01 and p < 0.05,
      respectively). In contrast, the debrisoquin urinary metabolic ratio, a measure of
      CYP2D6, was unaffected. The excretion of hydroxylamine dapsone-a putative probe
      of CYP3A activity-was reduced by 40% +/- 30% (p < 0.03) in white subjects but not
      in Chinese subjects. CONCLUSIONS: Omeprazole selectively inhibits the in vivo
      metabolism of S-mephenytoin, consistent with the predictions based on in vitro
      studies. The extent of interaction is greater in subjects of white European
      ancestry. It is to be expected that similar situations would also occur when
      omeprazole is coadministered with other substrates of CYP2C19.

PMID- 8873689
TI  - Analysis of the variability in the pharmacokinetics and pharmacodynamics of
      bumetanide in critically ill infants.
AB  - OBJECTIVES: Account for the interindividual variability in the pharmacokinetics
      and pharmacodynamics of bumetanide after intravenous administration of single
      doses to critically ill infants. METHODS: This prospective open-label study was
      carried out in the pediatric intensive care unit of a university-based children's
      hospital. Fifty-three volume-overloaded critically ill infants (age range, 4 days
      to 6 months) were divided into two groups: those with heart disease (31 infants)
      and those with lung disease (22 infants). Each patient received a single
      intravenous bolus dose of bumetanide. Doses, selected in sequential order, ranged
      from 0.005 to 0.100 mg/kg. Age was used as a continuous variable to determine its
      effects on the variability in the pharmacokinetics and pharmacodynamics of
      bumetanide. Hierarchical multiple regression analyses were used to assess the
      effects of age, disease, and other drugs on the variability in the effects of
      bumetanide. RESULTS: Total clearance, renal clearance, and nonrenal clearance of
      bumetanide all increased with age (p < 0.05), but the ratio of renal clearance to
      total clearance remained constant at about 0.4. Half-life and mean residence time
      decreased markedly in the first month of life (p < 0.05). Bumetanide excretion
      rate normalized for dose also increased with increasing age. Patients with lung
      disease exhibited a significantly greater clearance and shorter half-life (p <
      0.05) than those with heart disease, whereas volume of distribution was similar
      in both groups. The primary determinant of bumetanide excretion rate was the
      administered dose (73%). Dose-response curves for urine flow rate and electrolyte
      excretion were similar between disease groups. The time course of the effect of
      bumetanide excretion rate on pharmacodynamics responses was similar between
      disease groups, as was the duration of the diuretic effect. CONCLUSIONS: The
      pharmacokinetics of bumetanide were influenced significantly by age and disease.
      Differences in pharmacokinetics between patients with lung and heart disease were
      primarily due to differences in total clearance. The administered dose of
      bumetanide and age were positive determinants of bumetanide excretion rate and
      pharmacodynamic responses. Pharmacodynamic responses as a function of bumetanide
      excretion rate were not significantly different between disease groups.

PMID- 8873690
TI  - Dose-ranging evaluation of bumetanide pharmacodynamics in critically ill infants.
AB  - OBJECTIVES: Determine the diuretic effects of single intravenous doses of
      bumetanide in volume-overloaded critically ill infants. METHODS: A prospective,
      open-label study was carried out in 56 infants aged 0 to 6 months who required
      diuretic therapy. Each patient received a single intravenous dose of bumetanide.
      Doses selected in sequential order ranged from 0.005 to 0.10 mg/kg.
      Determinations of urine volume, electrolytes, creatinine levels, and osmolality
      were performed before (collected from -2 to -4 hours to time 0) and at 1, 2, 3,
      4, 6, and 12 hours after bumetanide dosing. Serum samples collected at time 0 and
      at 5, 15, 30, 60, 120, 180, 240, 360, and 480 minutes and urine aliquots
      collected at time 0, 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6 to 12 hours
      were analyzed for bumetanide concentration. Individual changes in urine flow rate
      and electrolyte excretion were plotted against corresponding bumetanide excretion
      rates, taken as the effective dose of the drug. RESULTS: Peak bumetanide
      excretion rates increased linearly with increasing doses of drug. Time course
      patterns for urine flow rate and electrolyte excretion were similar for all
      dosage groups. Urine flow rate and electrolyte excretion increased linearly up to
      a bumetanide excretion rate of approximately 7 micrograms/kg/hr and either
      plateaued (urine flow rate) or declined at a bumetanide excretion rate of > 10
      micrograms/kg/hr. Diuretic efficiency of bumetanide was maximal at doses of 0.005
      to 0.010 mg/kg but decreased at higher doses. CONCLUSIONS: Maximal diuretic
      responses occurred at a bumetanide excretion rate of about 7 micrograms/kg/hr,
      corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a
      proportionately higher bumetanide excretion rate but no increased diuretic
      effect. Lower doses of bumetanide had the greatest diuretic efficiency,
      suggesting that continuous infusion of low doses of bumetanide or intermittent
      low-dose boluses may produce optimal diuretic responses in critically ill
      infants.

PMID- 8873691
TI  - Substance P in human hand veins in vivo: tolerance, efficacy, potency, and
      mechanism of venodilator action.
AB  - OBJECTIVES: To study potency, efficacy, development of tolerance, and mechanism
      of action of substance P, an endothelium-dependent vasodilator neurokinin, in
      human hand veins in vivo. METHODS: Thirty-three healthy subjects were studied
      with use of the hand vein compliance technique. In hand veins preconstricted with
      the alpha 1-agonist phenylephrine, substance P and antagonists of nitric oxide
      formation (L-NG-mono-methyl-arginine, L-NMMA), adenosine triphosphate (ATP)
      dependent potassium channels (glyburide), angiotensin converting enzyme
      (enalaprilat), and cyclooxygenase (acetylsalicylic acid) were infused and the
      venodilator effect was measured. RESULTS: Substance P proved to be the most
      potent venodilator known thus far (the dose-rate exerting 50% of mean maximum
      dilation [ED50], geometric mean: 0.105 pmol/min). Rapid development of tolerance
      occurred in seven of eight volunteers studied. Glyburide decreased the
      venodilator action of a single dose of substance P (1.5 pmol/min) from 81% to 28%
      of baseline venodilation (p < 0.05), suggesting that substance P acts through
      release of endothelium-derived hyperpolarizing factor. The cyclooxygenase
      inhibitor acetylsalicylic acid reduced substance P-induced venodilation from 53%
      +/- 7% to 34% +/- 8% (p < 0.05), whereas L-NMMA had no effect. CONCLUSIONS:
      Unlike in other vessels, substance P-induced venodilation in hand veins is not
      mediated through nitric oxide but to a significant extent through a glyburide
      sensitive pathway. Therefore it appears likely that substance P activates ATP
      dependent potassium channels on vascular smooth muscle cells through the release
      of endothelium-derived hyperpolarizing factor.

PMID- 8873692
TI  - Dietary salt restriction increases vascular insulin resistance.
AB  - BACKGROUND: Recent studies have shown that insulin has a direct vasodilator
      effect and that vascular sensitivity to insulin is impaired in hypertension. How
      the vasodilator effect of insulin is regulated physiologically is unknown. It has
      been appreciated that salt restriction may have adverse effects on glucose and
      lipid metabolism--processes regulated by insulin. To determine whether dietary
      salt restriction might affect vascular sensitivity to insulin, we studied 13
      subjects (including eight borderline hypertensive subjects and five normotensive
      subjects) after 1 week of a normal sodium diet (240 mEq/day) and after 1 week of
      a low-sodium diet (20 mEq/day) with a randomized, double-blind crossover design.
      METHODS AND RESULTS: Vascular sensitivity to insulin was assessed with the dorsal
      hand vein linear variable differential transformer technique. When the "normal"
      salt diet was given, vascular sensitivity for insulin was significantly less
      (i.e., dose that produced the half-maximal response [ED50] insulin was higher) in
      hypertensive subjects (ED50 insulin for hypertensive subjects, 5.75 milliunits
      (mU)/min; ED50 insulin for normotensive subjects, 0.23 mU/min; p < 0.05).
      Vascular sensitivity to insulin was inversely correlated with mean arterial
      pressure and plasma norepinephrine concentration. When the low salt diet was
      given, vascular sensitivity to insulin decreased in both the normotensive and
      hypertensive groups, paralleling an increase in plasma norepinephrine. Blood
      pressure was not significantly decreased by reducing salt intake. CONCLUSION: In
      these younger normotensive and hypertensive subjects, dietary salt restriction
      increases resistance to the vasodilating effects of insulin.

PMID- 8873693
TI  - Pharmacokinetic and pharmacodynamic profiles of sumatriptan in migraine patients
      with headache recurrence or no response.
AB  - OBJECTIVES: Sumatriptan is effective in the acute treatment of migraine. However,
      about 15% of patients with migraine do not experience headache relief after
      sumatriptan, and up to 40% may experience recurrence of headache within 24 hours.
      We studied whether pharmacokinetic or pharmacodynamic differences may explain
      these different clinical effects. METHODS: We compared the pharmacokinetic
      profiles of subcutaneous sumatriptan in 14 patients who consistently had headache
      relief without headache recurrence, in 12 patients who had headache recurrence in
      every attack, and in six patients who did not have headache relief after
      sumatriptan. Because the antimigraine action of sumatriptan may be mediated
      through vasoconstriction of cranial blood vessels, we also compared in these
      patients changes in blood vessel diameter and blood velocity in the common,
      internal, and external carotid arteries. RESULTS: Despite sufficient power of the
      study, no important differences in pharmacokinetic and pharmacodynamic profiles
      between the three patient groups were detected. CONCLUSION: Headache recurrence
      and lack of headache relief after sumatriptan do not appear to be explained by
      pharmacokinetic or pharmacodynamic differences between patients, which may be an
      important finding for the development of novel antimigraine drugs.

PMID- 8873694
TI  - Cardiovascular adaptation to orthostatic stress during vasodilator therapy.
AB  - BACKGROUND: Orthostatic hypotension is a dangerous problem in elderly patients,
      often exacerbated by vasodilator medications. Age- and disease-related
      impairments in cardioacceleration and diastolic ventricular function may make
      older patients particularly vulnerable to the hypotensive effects of these drugs.
      Therefore we aimed to determine mechanisms of postural blood pressure regulation
      in elderly patients with coronary artery disease and to compare the effects of
      isosorbide dinitrate and nicardipine hydrochloride on postural blood pressure
      homeostasis in these patients. METHODS: Twenty elderly subjects with stable
      coronary artery disease (age, 76 +/- 4 [SD] years) underwent a baseline
      evaluation followed by a double-blind, randomized crossover comparison of
      nicardipine (20 mg by mouth t.i.d.) versus isosorbide (20 mg by mouth t.i.d.).
      Doppler echocardiography and a 15-minute 60-degree head-up tilt test were
      conducted on no study medications and then after successive 3-week treatment
      periods with nicardipine or isosorbide. Blood pressure, heart rate, vascular
      resistance, cardiac output, and spectral characteristics of heart rate and blood
      pressure variability were measured before and during each tilt. RESULTS:
      Isosorbide treatment was associated with a higher prevalence of symptoms of
      cerebral hypoperfusion and a failure to increase systemic vascular resistance
      during tilt. While taking isosorbide subjects were able to preserve cardiac
      output and maintain upright blood pressure through enhanced cardioacceleration.
      During nicardipine treatment systemic vascular resistance and low-frequency blood
      pressure variability were reduced, but the ability to increase systemic vascular
      resistance during tilt was preserved. CONCLUSIONS: Although nicardipine may
      decrease vascular responsiveness to sympathetic activation, the baroreflex
      mediated vasoconstrictor response to upright tilt remains intact. In contrast,
      isosorbide impairs the systemic vascular response to orthostatic stress in
      elderly patients with stable coronary artery disease.

PMID- 8873696
TI  - Join the AAP.

PMID- 8873695
TI  - Effects of benazepril and nicardipine on microalbuminuria in normotensive and
      hypertensive patients with diabetes.
AB  - Diabetic nephropathy is the most frequent cause of chronic renal failure. The
      onset of microalbuminuria in patients with diabetes mellitus, which seems to be
      related to blood pressure and the control of glycemia, is predictive of the
      development of true proteinuria. This multicenter, single-blind, randomized study
      examined the effects of benazepril and nicardipine on overnight microalbuminuria
      in 57 normotensive and 46 hypertensive diabetic patients. At the end of a 3-month
      placebo run-in period, the patients were stratified on the basis of the presence
      or absence of arterial hypertension and, within each stratum, randomized to
      receive one daily tablet of 10 mg benazepril or one tablet of 20 mg nicardipine
      twice daily for 6 months. Renal hemodynamics was investigated in 25 patients.
      Both drugs decreased overnight microalbuminuria throughout the study period, but
      benazepril was more effective than nicardipine (p = 0.025); in the patients with
      hypertension, both drugs led to a similar marked reduction in systolic and
      diastolic blood pressure. This study shows that benazepril was more effective
      than nicardipine in reducing overnight microalbuminuria in patients with diabetes
      mellitus, independently of their antihypertensive properties.

PMID- 8873697
TI  - Enoxaparin for thromboembolism prophylaxis in spinal injury: preliminary report
      on experience with 105 patients.
AB  - Venous thromboembolism continues to be a major cause of morbidity and mortality
      in patients with spinal injury (SI). Recently, we reported on the effectiveness
      and safety of a low molecular weight heparin (LMWH), tinzaparin, in preventing
      deep vein thrombosis in motor-complete SI patients. Recently, another LMWH,
      enoxaparin, was approved by the United States Food and Drug Administration for
      prevention of thromboembolism in hip and knee replacement surgery. Since its
      approval, we have used 30 mg of enoxaparin subcutaneously every 12 h as routine
      prophylaxis in all hospitalized SI patients. In this retrospective study, we
      present an analysis of safety and efficacy of the first six months experience,
      during which 105 patients received the drug. No patient developed clinical
      evidence of thromboembolism, and none of the 60 venous ultrasound examinations
      showed a deep vein thrombus. Eleven patients had evidence of hemorrhage, but the
      LMWH was considered to have contributed to the bleeding in only three. This
      additional experience with enoxaparin reinforces our previous conclusion that
      LMWHs are safe and effective thromboprophylactic agents in SI patients.

PMID- 8873698
TI  - Pronator teres reflex: reliability and normal value.
AB  - The pronator reflex has been used clinically and electrophysiologically to
      evaluate the sixth and seventh cervical roots (C-6, C-7). This has been proven to
      be the result of stretching the pronator teres muscle. We examined 25 healthy
      individuals with surface electromyogram to establish electrophysiologically the
      reproducibility and reliability of this reflex, in addition to finding the 95%
      confidence interval (C.I.) for the latency for both males and females and to
      correlate it with the arm length. Standard procedure was used for all people. To
      elicit the pronator teres reflex, the volar report of the distal radius was
      struck by the hammer with the forearm in neutral position and the elbow flexed at
      90 degrees. The response was pronation of the forearm. A reproducible diphasic
      response was found in all individuals. The mean latency was 15.9 (+/-1.3) ms with
      the 95% C.I. 16.8 for females and 17.4 (+/- 1.4) ms with the 95% C.I. 18.7 for
      males. The data were collected to be used for further evaluation of C-6, C-7
      radiculopathy.

PMID- 8873699
TI  - Spinal muscular atrophy: kinematic breathing analysis.
AB  - Twelve children with spinal muscular atrophy (SMA) type 2 and 13 children without
      physical disability underwent kinematic analysis of thoracoabdominal volume
      changes when breathing spontaneously and when breathing deeply. A very accurate
      optical method of kinematic analysis was used. Volumes were partitioned into
      upper thoracic, lower thoracic, and abdominal compartments. Abdominal volume
      increases accounted for 96% of the normal tidal volumes and 87% of the deep
      breathing volumes for the patients, but only 74 and 41% of the volumes,
      respectively, for the controls. For the patients the upper thoracic contribution
      to breathing volumes was --1.7% for normal tidal volumes and 0.3% for deep
      breathing volumes. Patients with less upper thoracic kinematic reserve were also
      found to be more likely to have chronic nocturnal hypoventilation. We conclude
      that kinematic analysis can be helpful in determining differences in regional
      lung mobility and risk for nocturnal ventilatory dysfunction for children with
      SMA. Therapeutic interventions need to be addressed to maintain thoracic
      kinematic reserve and lung compliance and, thereby, to facilitate more normal
      lung growth and the ability to cough.

PMID- 8873700
TI  - Bromocriptine in the treatment of post-polio fatigue: a pilot study with
      implications for the pathophysiology of fatigue.
AB  - Fatigue is the most commonly reported and most disabling of all post-polio
      sequelae (PPS). Bromocriptine mesylate (Parlodel) was employed in a placebo
      controlled trial in five survivors of paralytic polio who continued to report
      moderate to severe daily fatigue after complying with the conservative treatments
      prescribed for PPS. Placebo was given for 4 wk followed by increasing doses of
      bromocriptine mesylate, administered at 12:00 pm for 28 days, which reached a
      total dose of 12.5 mg/day. Three subjects reported marked symptom improvement on
      bromocriptine but not on placebo. Their reported difficulty with attention,
      concentration, word finding, mind wandering, memory, thinking clearly, and
      fatigue on awakening was significantly negatively correlated with days on
      bromocriptine but not with days on placebo. Before the drug trial began,
      responders had clinically impaired performance on neuropsychologic tests of
      attention and information processing speed, more than twice as many
      hyperintensities on magnetic resonance imaging of the brain, abnormally low
      fasting adrenocorticotropic hormone levels, and nearly double the mean plasma
      prolactin level compared with nonresponders. The implications of these findings
      for the pathophysiology of fatigue are discussed. A double-blind, placebo
      controlled, multicenter study will be needed to confirm bromocriptine's efficacy
      in treating attentionally and neurophysiologically impaired polio survivors whose
      severe and disabling fatigue does not respond to conservative therapies.

PMID- 8873701
TI  - Quantitative measurement of improvement in sitting balance in children with
      spastic cerebral palsy after selective posterior rhizotomy.
AB  - Severe muscular spasticity encountered frequently in patients with spastic
      cerebral palsy not only affects patient locomotor function but also causes
      musculoskeletal complications. Significant reduction of spasticity over pelvis
      and lower limbs after selective posterior rhizotomy (SPR) results in improvement
      of trunk stability, locomotor function, and function of upper limbs also. The
      purpose of this study was to investigate the difference of sitting balance before
      and after SPR using a quantitative measurement in sitting stability represented
      as dispersion index provided by the Chattecx Balance System. Seventeen children
      with spastic cerebral palsy, ten boys and seven girls, with a mean age of 5.06
      yr, underwent SPR. Their sitting stability under static and dynamic, visual and
      nonvisual testing conditions was assessed before SPR and three mo after SPR.
      Their sitting balance showed significant improvement at postoperative evaluation
      except for the static-nonvisual testing condition. Dispersion index under the
      dynamic testing condition was significantly higher than under the static testing
      condition, which implies that dynamic sitting balance was worse than static
      sitting balance in these patients. There was no statistical difference of sitting
      performance between visual and nonvisual condition both preoperatively and
      postoperatively. Quantitative measurement of dispersion index provided by the
      Chattecx Balance System offers an objective evidence of improvement in sitting
      balance for children after SPR.

PMID- 8873702
TI  - Assessment of upper limb function in hemiplegia by measuring transcutaneous
      oxygen tension.
AB  - To investigate whether the noninvasive determination of transcutaneous oxygen
      tension (TcO2) can be used to evaluate the degree of hemiplegia, we measured TcO2
      before and after a 2-mo rehabilitation course in 12 patients with hemiplegia
      caused by cerebrovascular diseases. All patients with no evidence of heart
      failure (ejection fraction evaluated by echocardiogram: 68.7 +/- 6.4%) began to
      receive conventional physical therapy a few days after the onset of stroke. The
      measurement of TcO2 was performed at 9:00 a.m. with an electrode placed on the
      skin surface of the flexion side of the forearm 5 cm distal to the elbow. Before
      rehabilitation, the difference in TcO2 between the paralyzed and healthy upper
      limbs ((delta)TcO2) in patients at Brunnstrom's stage V was significantly lower
      than that in patients at stages II, III, and IV (P < 0.05, P <0.01, and P < 0.01,
      respectively). After rehabilitation, (delta)TcO2 in patients at Brunnstrom's
      stage V was significantly lower than that in patients at stage III(P < 0.05). The
      (delta)TcO2 in the patients with severe hemiplegia was larger than that in
      patients with slight hemiplegia. In addition, TcO2 at the paralyzed upper limb
      increased significantly after rehabilitation (before 62.7 +/- 10.5 mm Hg; after
      71.9 +/- 9.0 mm Hg; P < 0.05), although arterial blood oxygen tension (PaO2) did
      not. Therefore, the TcO2 determination may be useful in assessing the degree of
      hemiplegia in upper limbs.

PMID- 8873703
TI  - Validity of a brief outpatient functional assessment measure.
AB  - Aspects of validity are investigated with a brief functional assessment measure
      among outpatients undergoing rehabilitation for musculoskeletal problems. The
      Medical Rehabilitation Follow Along measure (MRFA) currently has screening,
      musculoskeletal, neurologic, and multiple sclerosis forms. In this study, the 31
      item musculoskeletal form of the MRFA is compared with and contrasted to a
      measure of general health status, the Medical Outcomes Trust SF-36. Content,
      construct, and criterion validity are addressed using scale scores before (n =
      94) and after (n = 48) outpatient rehabilitation. Scale scores are compared with
      therapists' ratings of improvement. The results provide support for the validity
      of inferences made from scale scores of the MRFA for persons with musculoskeletal
      problems. Applications of the MRFA, including screening, monitoring, and outcome
      assessment are discussed for clinical management, measuring treatment
      effectiveness, and program evaluation.

PMID- 8873704
TI  - Relationship between Glasgow coma scale and functional outcome.
AB  - The Glasgow Coma Scale (GCS) is routinely used in the acute care setting after
      traumatic brain injury (TBI) to guide decisions in triage, based on its ability
      to predict morbidity and mortality. Although the GCS has been previously
      demonstrated to predict mortality, efficacy in prediction of functional outcome
      has not been established. The purpose of this study was to assess the value of
      the acute GCS in predicting functional outcome in survivors of TBI. This study
      used the Multicenter National Institute on Disability and Rehabilitation Research
      TBI Model Systems database of 501 patients who had received acute medical care
      and inpatient rehabilitation within a coordinated neurotrauma program for
      treatment of TBI. Initial and lowest 24 hr GCS scores were correlated with the
      following outcome measures: the Disability Rating Scale (DRS), Rancho Los Amigos
      Levels of Cognitive Functioning Scale (LCFS), and cognitive and motor components
      of the Functional Independence Measure (FIM(SM)-COG and FIM(SM)-M). Outcome data
      were collected at admission to and discharge from the inpatient TBI
      rehabilitation unit. Correlation analysis revealed only modest, but statistically
      significant, relationships between initial and lowest GCS scores and outcome
      variables. Initial and lowest GCS score comparison with outcome demonstrated the
      following correlation coefficients: admission DRS, -0.25 and -0.28; discharge
      DRS, -0.24 and -0.24; admission LCFS, 0.31 and 0.33; discharge LCFS, 0.27 and
      0.25; admission FIM-COG, 0.36 and 0.37; discharge FIM-COG, 0.23 and 0.23;
      admission FIM-M, 0.31 and 0.31; discharge FIM-M, 0.25 and 0.21. The GCS as a
      single variable may have limited value as a predictor of functional outcome.

PMID- 8873705
TI  - Correlation of back extensor strength with thoracic kyphosis and lumbar lordosis
      in estrogen-deficient women.
AB  - Aging and osteoporosis have been associated with skeletal changes. Back extensor
      strengthening exercises are highly recommended for management of back pain,
      especially back pain related to osteoporosis. To our knowledge, the correlation
      of thoracic kyphosis, lumbar lordosis, and sacral inclination with back extensor
      strength, physical activity, and bone mineral density has not been critically
      studied in healthy, active, estrogen-deficient women. In a study of 65 such women
      (ages 48-65 yr), back extensor strength, bone mineral density, and physical
      activity score were evaluated and measured. These factors were then correlated
      with radiographic factors: (1) vertebral body ratios (anterior/posterior height)
      calculated for each vertebra from T-4 through L-5; (2) kyphosis index determined
      by adding the anterior heights of each vertebral body, T-4 through T-12, and then
      dividing the total by the corresponding sum of the posterior heights of each
      vertebral body; (3) thoracic kyphosis; (4) lumbar lordosis; and (5) sacral
      inclination. Back extensor strength had a significant negative correlation with
      thoracic kyphosis (r = -0.30, P = 0.019) and a positive correlation with lumbar
      lordosis (r = 0.26, P = 0.048) and sacral inclination (r = 0.34, P = 0.009).
      However, bone mineral density and physical activity score did not show any
      significant correlations with the radiographic factors. The results indicate that
      the stronger the back extensor, the smaller the thoracic kyphosis and the larger
      the lumbar lordosis and sacral inclination. We conclude that back extensor
      strength is an important determinant of posture in healthy women. However,
      prescribing back extensor strengthening exercises alone may also increase lumbar
      lordosis, which is not desirable.

PMID- 8873706
TI  - The proportional work of lifting the center of mass during walking.
AB  - The present study determined the proportion of energy consumption used to lift
      the center of mass vertically during walking. By assuming that the vertical
      oscillations of the trunk were identical to those of the center of mass, the
      complexity of studying the human gait was simplified. The work performed on the
      center of mass, defined as lift work, was calculated using the subject's mass and
      the vertical displacement of the trunk. Compensating for the fact that human
      muscles are approximately 25% efficient in performing external work, the
      mechanical work was compared with the total energy expenditure, determined using
      an expired air analysis. At 1.34 and 1.79 m/s, 53.2 +/- 9.3% and 62.8 +/- 8.6%,
      respectively, of the total energy can be explained by lift work. At 0.45 and 0.90
      m/s, the proportions are considerably less, 21.6 +/- 6.6% and 37.6 +/- 8.2%,
      respectively. These findings provide a rationale for why the metabolic energy
      cost per unit distance is greater at slower speeds than comfortable or fast
      speeds of walking. The total energy consumption can be accounted for by changes
      in the potential and kinetic energies and internal muscular work, defined as the
      less readily observable work probably needed for balance. The present study
      demonstrated that the metabolic energy cost of changing the potential energy of
      the center of mass during walking is significantly less relative to the total
      energy consumption at slower speeds than at higher speeds. Because kinetic energy
      is proportional to the square of the velocity, the metabolic energy cost of
      changing this energy is relatively small at slower speeds. Internal muscular work
      must therefore play a large role in total energy consumption at slow speeds of
      walking.

PMID- 8873707
TI  - Transfers from a hospital-based rehabilitation unit caused by medical
      complications.

PMID- 8873708
TI  - The physiatrist as diagnostician: avoiding the pitfalls of stenotic thinking.

PMID- 8873710
TI  - Emergency stenting of malignant obstruction of the upper airways: long-term
      follow-up with two types of silicone prostheses.
AB  - OBJECTIVE: We evaluated the long-term prognosis of stents placed on an emergency
      basis in the trachea and its bifurcation for malignant stenosis. METHODS: We
      retrospectively analyzed all bronchologic treatments of obstructing airway
      lesions from January 1993 to December 1995. RESULTS: We report on 10 patients
      with severe malignant "mixed-type" obstruction of the proximal trachea or distal
      trachea plus both main-stem bronchi. They had far-advanced inoperable tumor
      (esophageal cancer: n = 4; lung cancer: n = 3; recurrent laryngeal, uvula, and
      thyroid cancer: n = 1 each). Emergency treatment consisted of a dilating bougie
      maneuver followed by the insertion of a large one-way (n = 4) or Y-shaped
      silicone prosthesis (n = 6). After the intervention, there was a long-lasting
      clinical improvement. Median survival from stent insertion was 8 months for all
      patients irrespective of tumor type; it was 5 months for patients with lung
      carcinoma and 8 months for those with esophageal cancer. The results are in
      accordance with other studies using different therapeutic modalities. Stent
      exchange was necessary in five patients. Main reasons were continuing tumor
      growth beyond the proximal and distal boundaries and recurrent productive
      bronchial infection. Patients died of pneumonia (n = 4), pulmonary lymphatic
      spread (n = 1), cardiac failure (n = 2), and fatal hemorrhage (n = 1). As of
      December 1995, three patients were still alive 2, 5, and 8 months after
      implantation. CONCLUSIONS: As evidenced by clinical efficiency and length of
      palliation, endoscopic placement of silicone-based one-way and bifurcational
      prostheses in far-advanced tumor of the central airways is technically feasible
      and ethically justifiable.

PMID- 8873711
TI  - Pulmonary resection for metastatic colorectal cancer: experiences with 159
      patients.
AB  - We reviewed the clinical courses of 159 patients between February 1967 and May
      1995 for the purpose of examining the survival of patients who had pulmonary
      resection for metastatic colorectal cancer. The cumulative survivals at 5 years
      and 10 years were 40.5% and 27.7%, respectively. Fifteen patients (10%) were
      alive more than 10 years after the thoracotomy without any evidence of
      recurrence. The cumulative survival at 5 years for 39 patients who had hepatic
      metastases before thoracotomy was 33%. There was a statistically significant
      difference in survival between patients with extrapulmonary metastases and those
      with only intrapulmonary metastases before thoracotomy. The number of pulmonary
      metastases and the presence of hilar or mediastinal lymph node metastases
      affected postthoracotomy survival. There was no significant difference in
      survival on the basis of sex, age, location of the primary cancer, size of the
      pulmonary tumors, mode of operation, or disease-free interval. Surgical treatment
      for pulmonary metastases from colorectal cancer in selected patients, even those
      who had hepatic metastases before thoracotomy, might improve prognosis.

PMID- 8873712
TI  - Bilateral volume reduction surgery for diffuse pulmonary emphysema by video
      assisted thoracoscopy.
AB  - We prospectively studied the surgical aspects, functional results, and
      complications of video-assisted bilateral thoracoscopic volume reduction surgery
      in patients with severe diffuse pulmonary emphysema. METHODS: Fifteen men and
      five women with a mean age of 64 years (range 42 to 78 years) whose daily
      activity was substantially impaired by severe airflow obstruction and
      hyperinflation underwent thoracoscopic volume reduction surgery. The prospective
      preoperative assessment and postoperative assessment at 3 months included (1)
      pulmonary function studies, (2) grading of dyspnea, and (3) exercise performance;
      pulmonary function tests were also performed immediately before discharge from
      the hospital. RESULTS: There was no perioperative mortality. All patients left
      the hospital after a median stay of 15 days (6 to 27 days). Only seven patients
      had a prolonged chest tube drainage time (>7 days). At 3 months the mean (+/-
      standard deviation) forced expiratory volume in 1 second had improved by 42% (+/
      3.8%), from 0.80 L (+/-0.23) to 1.09 L (+/-0.28) (p < 0.001); residual volume had
      decreased from 5.8 L (+/-1.5) to 4.4 L (+/-1.0) (p < 0.001). Shortly before
      discharge the forced expiratory volume in 1 second was already 1.10 L (+/-0.26).
      The median 12-minute walking distance increased from 495 m (35 to 790 m) to 688 m
      (175 to 1035 m) (p < 0.001) and the mean maximal oxygen consumption from 10 ml/kg
      per minute (+/-2.5) to 13 ml/kg per minute (+/-2.3) (p < 0.0005). The patients
      reported a substantial relief of dyspnea with a mean decrease in the Medical
      Research Council score from 3.4 to 1.8.

PMID- 8873713
TI  - Central venous thrombosis after cardiac operations in children.
AB  - To evaluate the incidence, mortality, late outcome, and cause of central venous
      thrombosis after pediatric heart operations and other operations performed with
      cardiopulmonary bypass, we identified patients with postoperative central venous
      thrombosis during a 10-year period at a single pediatric hospital. There had been
      1591 open heart (with bypass) and 1086 closed heart (no bypass) procedures and 13
      operations with cardiopulmonary bypass for extracardiac indications. There were
      20 patients with central venous thrombosis, yielding incidences of 1.1% and 0.2%
      after cardiopulmonary bypass and after closed heart operations, respectively.
      When neonates were compared with older children (1 to 119 months of age)
      undergoing heart procedures, a tenfold increase (5.8% vs 0.6%) (p < 0.001) in the
      incidence of central venous thrombosis was observed. The mortality was eight of
      20 (40%). Central venous thrombosis contributed to seven deaths and it was a
      direct cause of one death. Ten patients were reinvestigated 5 to 108 months after
      central venous thrombosis. The outcome of surgery was excellent in eight. Two had
      residual thrombosis, but this was not hemodynamically significant to the
      cardiorespiratory condition of the patients. During or preceding thrombosis, low
      levels of antithrombin III and/or protein C and high levels of the plasminogen
      activator inhibitor were observed in five of the patients. A congenital
      thrombotic risk factor, "resistance to activated protein C," was found in two of
      12 tested patients with central venous thrombosis (17%). In conclusion, central
      venous thrombosis, especially in neonates, is an important cause of morbidity and
      mortality after cardiac operations. The cause is multifactorial, with
      contributions from multiple acquired thrombophilic coagulation abnormalities, and
      resistance to activated protein C may act as a risk factor for thrombosis already
      during neonatal period.

PMID- 8873714
TI  - The endothelin antagonist bosentan: hemodynamic effects during normoxia and
      hypoxic pulmonary hypertension in pigs.
AB  - In this study, we investigated the hemodynamic effects and receptor-blocking
      properties of the nonselective endothelin antagonist bosentan in pigs during
      normoxia and acute hypoxia. Hypoxic pulmonary hypertension was induced by
      decreasing the fraction of inhaled oxygen to 0.1. In a control group of pigs,
      hemodynamic parameters proved to be stable through 2 hours of hypoxia. Infusions
      of endothelin-1, endothelin-3, and sarafotoxin 6c into the pulmonary artery
      resulted in pulmonary and systemic vasoconstriction during normoxia, whereas
      endothelin administration during hypoxic pulmonary hypertension resulted in
      pulmonary vasodilation. After administration of bosentan, the vasopressor effect
      of endothelin-1 during normoxia was significantly attenuated and the pulmonary
      vasodilatory effect of endothelin-1 during hypoxia was reduced. Furthermore, the
      development of hypoxic pulmonary hypertension was significantly reduced by
      bosentan. In contrast, bosentan did not influence the pulmonary vasopressor
      response to the thromboxane mimic U-46619. We therefore conclude that vasopressor
      endothelin receptors seem to be activated by endogenous endothelin released
      during hypoxia, leading to an increase in the pulmonary vascular tone.

PMID- 8873715
TI  - Anatomically based ablation of atrial flutter in an acute canine model of the
      modified Fontan operation.
AB  - BACKGROUND: Lateral tunnel total cavopulmonary connection, also called the
      modified Fontan operation, uses a baffle through the right atrium. We
      established, in an acute canine model, that atrial flutter after total
      cavopulmonary connection revolves around a line of conduction block imposed by
      the free wall lateral tunnel suture line. We hypothesized that a line of
      conduction block between the free wall total cavopulmonary connection suture line
      and the tricuspid anulus would interrupt atrial flutter in this model. OBJECTIVE:
      Our objective was to determine whether a cryolesion placed between the free wall
      total cavopulmonary connection suture line and the tricuspid anulus would
      terminate atrial flutter in an acute canine model. METHODS: Seven adult dogs
      underwent median sternotomy and institution of cardiopulmonary bypass. A suture
      line was placed through a right atriotomy to simulate total cavopulmonary
      connection lateral tunnel construction. Form-fitting 253-point biatrial
      endocardial mapping electrodes were placed via bilateral ventriculotomies. Atrial
      flutter was induced by atrial burst pacing. A cryothermal lesion was then placed
      between the free wall total cavopulmonary connection suture line and the
      tricuspid anulus in the low lateral right atrium (i.e., CRYO 1 procedure), and
      reinduction of atrial flutter was attempted. If atrial flutter was reinduced, the
      cryolesion was modified superiorly to include the caudal portion of the atriotomy
      (i.e., CRYO 2 procedure). Activation sequence maps were generated for sinus
      rhythms before and after the cryolesions were placed and for induced arrhythmias.
      RESULTS: In all seven cases, atrial flutter was inducible after suture line
      placement, before placement of a cryolesion. The reentrant circuit incorporated
      both caval orifices in five of seven cases and was successfully ablated by the
      CRYO 1 approach in each case. Atrial flutter was not inducible after placement of
      the CRYO 2 lesion in the remaining two cases, in which breakthrough of the wave
      front occurred across the lateral tunnel suture line in the intercaval region.
      Activation sequence maps of sinus rhythm after placement of the cryolesions
      demonstrated a conduction block at the site of the lesion. CONCLUSIONS: A linear
      cryothermal lesion placed between the free wall aspect of the total cavopulmonary
      connection suture line and the tricuspid anulus created a line of conduction
      block that successfully ablates atrial flutter in the canine model.

PMID- 8873716
TI  - Nosocomial infections in patients having cardiovascular operations: a
      multivariate analysis of risk factors.
AB  - A total of 970 adult patients undergoing cardiovascular operations during a 1
      year period were eligible for a case-control study on the risk factors for
      nosocomial infection. Cases were defined as patients in whom a postoperative
      infection developed. Every case was paired with one uninfected subject.
      Nosocomial infection occurred in 89 (9.2%) patients. A total of 120 episodes of
      infection were diagnosed (1.3 episodes per patient). The infection ratio was
      12.4%. Surgical site infection was the most common (5.6%), followed by pneumonia
      (3.2%), urinary tract infection requiring the use of intravenous antibiotics
      (1.8%), deep surgical site (0.9%), and bacteremia (0.7%). Advanced age, urgent
      intervention, duration of surgical procedure, blood transfusion, and use of
      invasive procedures (urinary catheter, chest tubes, nasogastric tube passage)
      were significantly associated with infection in the bivariate analysis.
      Nosocomial infection resulted in a significant increase in the length of hospital
      stay. Cases showed an almost fivefold greater risk of death than controls (odds
      ratio, 4.73; 95% confidence interval, 1.11 to 6.83; p = 0.009). Age older than 65
      years, female sex, and mode of surgical intervention were selected in the
      multivariate analysis for patients undergoing cardiac operations, whereas general
      anesthesia or assisted ventilation, central venous catheter, and blood
      transfusion were the variables selected for patients undergoing operation for
      vascular disorders. In summary, the recognition of risk factors for postoperative
      infection in patients undergoing cardiovascular surgical procedures may
      contribute to improve their prognosis and to more organized surveillance and
      control activities in the hospital environment.

PMID- 8873717
TI  - Mapping of septal ventricular tachycardia: clinical and experimental
      correlations.
AB  - In patients with chronic myocardial infarction, ventricular tachycardia
      originating in the interventricular septum may account for a significant number
      of arrhythmia recurrences after direct ablative operations. We used total
      computer-assisted cardiac mapping (epicardial sock, left and right ventricular
      endocardial balloon electrode arrays) to assess whether tachycardia originating
      in deep or right-sided layers of the interventricular septum is associated with a
      specific pattern of epicardial activation sequence. We performed these studies
      during operations in 18 patients and during experiments in 12 dogs in which a
      septal myocardial infarction was produced by ligating the anterior septal
      coronary artery. Intraseptal needle electrodes were plunged into the septum of
      all animal preparations to generate pace-mapping data and to obtain intraseptal
      recordings (six preparations) during reentrant ventricular tachycardia induced by
      programmed stimulation. In addition, pace-mapping data of infarcted canine heart
      preparations were compared with those of nine healthy heart preparations. In the
      clinical study, 31 ventricular tachycardias with a septal site of origin were
      analyzed. Twenty tachycardias displayed an epicardial breakthrough in the area of
      the interventricular groove, whereas 11 had an epicardial breakthrough in the
      right ventricular free wall. Biventricular endocardial mapping revealed that left
      septal endocardial activation preceded right septal activation in the former and
      that right septal activation occurred earlier in the latter. In the experimental
      study, 14 ventricular tachycardias (cycle length 146 +/- 34 msec) were induced by
      programmed stimulation in 11 infarcted heart preparations. Eight tachycardias
      displaying an epicardial breakthrough on the right ventricle were found to
      originate in the right ventricular septal subendocardial layers, whereas six
      tachycardias in which the epicardial breakthrough occurred on the anterior
      interventricular groove originated in the left ventricular septal subendocardial
      layers. The epicardial breakthrough preceded the left ventricular endocardial
      breakthrough in six tachycardias (85.7%) originating in intermediate or right
      ventricular septal layers, but in only one of five tachycardias originating in
      the left ventricular septal layers. In the pace-mapping study, the epicardial
      breakthrough shifted progressively from the right ventricular free wall toward
      the interventricular groove area in response to pacing from the right,
      intermediate, and left ventricular thirds of the basal septum. This relationship
      was similar for infarcted and noninfarcted hearts, although transseptal
      conduction time was prolonged in infarcted hearts (45 +/- 10 msec vs 33 +/- 7
      msec, p < 0.01). Therefore the information integrated from the localization of
      the epicardial breakthrough and the relative timing between the epicardial and
      the left ventricular endocardial breakthroughs can be used to estimate the depth
      of the site of origin of septal ventricular tachycardias. This study confirms
      that a three-dimensional view of the substratum of ventricular tachycardia can be
      derived from simultaneous epicardial and left ventricular endocardial mapping and
      can provide a superior basis for therapeutic interventions.

PMID- 8873718
TI  - Long-term outcome and quality of life of patients requiring multidisciplinary
      intensive care unit admission after cardiac operations.
AB  - Patients with organ failure or severe infection after cardiac operations may
      require prolonged stays in the intensive care unit. This study examined long-term
      mortality and determined quality of life for surviving patients in this group.
      This observational cohort study was conducted at Bichat Hospital, Paris, an
      academic tertiary care center. The study group consisted of 116 consecutive
      patients who underwent cardiac operations and were transferred to the
      multidisciplinary intensive care unit between January 1986 and December 1987.
      Patients referred for mediastinitis were automatically excluded. Respiratory
      failure (88.8%) and hemodynamic instability (81.9%) were the main causes of
      transfer; an infection was present in 23.3% of patients at entry into the
      intensive care unit. Twenty-seven patients (23.3%) died in the intensive care
      unit. Presurgical New York Heart Association functional class, postoperative
      bacteremia before admission to the intensive care unit, and severity of illness
      on admission to the intensive care unit were independent predictors of death in
      the intensive care unit. After an average follow-up of 81 months (range 70 to 93
      months), 69% of the patients alive at transfer from the intensive care unit were
      still alive. Preoperative New York Heart Association functional class was the
      only long-term independent prognostic factor. Quality of life, as evaluated by
      the Nottingham Health Profile, was good for more than 70% of the survivors and
      was not influenced by any recorded variables, with the exception of age.

PMID- 8873719
TI  - Exclusive use of arterial grafts in coronary artery bypass operations for three
      vessel disease: use of both thoracic arteries and the gastroepiploic artery in
      256 consecutive patients.
AB  - METHODS: From September 1989 to September 1994 we operated on a consecutive group
      of 256 patients with three-vessel disease in whom we used the right
      gastroepiploic artery together with both internal thoracic arteries. Vein grafts
      were not used in these patients. This population consisted of 233 men and 23
      women whose ages ranged from 31 to 77 years (mean age 57.8 years). RESULTS:
      Hospital morbidity and mortality were not directly related to the use of the
      gastroepiploic artery. Patency of the anastomoses in a subgroup of 56 patients
      (22%) a mean of 16 months after the operation was 98% for the left internal
      thoracic artery, 96% for the right internal thoracic artery, and 88% for the
      gastroepiploic artery. Five-year actuarial survival (including in-hospital
      deaths) was 95.9% and was related only to age. From discharge until the end of
      follow-up, two patients had a myocardial infarction, six patients underwent a
      reintervention procedure, and 18 patients had a return of angina pectoris.
      CONCLUSION: We conclude that the concomitant use of the gastroepiploic artery
      with the both internal thoracic arteries has low morbidity and mortality in
      patients with three-vessel disease operated on by experienced surgeons. At this
      moment, we have no reason to believe graft patency will deteriorate in the
      future. On the basis of these results, the knowledge that arteries are to be
      preferred over veins for coronary bypass grafting, and the absence of a leg
      incision, we believe this operative technique is superior to the use of venous
      grafts.

PMID- 8873720
TI  - Topography of cardiac ganglia in the adult human heart.
AB  - Published descriptions of the topography of cardiac ganglia in the human heart
      are limited and present conflicting results. This study was carried out to
      determine the distribution of cardiac ganglia in adult human hearts and to
      address these conflicts. Hearts obtained from autopsies and heart transplant
      procedures were sectioned, stained, and examined. Results indicate that the
      largest populations of cardiac ganglia are near the sinoatrial and
      atrioventricular nodes. Smaller collections of ganglia exist on the superior left
      atrial surface, the interatrial septum, and the atrial appendage-atrial
      junctions. Ganglia also exist at the base of the great vessels and the base of
      the ventricles. The right atrial free wall, atrial appendages, trunk of the great
      vessels, and most of the ventricular myocardium are devoid of cardiac ganglia.
      These findings suggest modifications to surgical procedures involving incisions
      through regions concentrated with ganglia to minimize arrhythmias and related
      complications. Repairs of septal defects, valvular procedures, and congenital
      reconstructions, such as the Senning and Fontan operations, involve incisions
      through areas densely populated with cardiac ganglia. The current standard
      procedure for orthotopic heart transplantation severs cardiac ganglia and their
      projections to nodal and muscular tissue. One modification of the current heart
      transplantation procedure, involving bicaval anastomosis, preserves atrial
      anatomy and the cardiac ganglia. Preservation of cardiac ganglia within the donor
      heart may provide additional neuronal substrate for intracardiac processing and
      targets for regenerating nerve fibers to the donor heart.

PMID- 8873721
TI  - Feasibility of aortic diameter measurement by multiplane transesophageal
      echocardiography for preoperative selection and preparation of homograft aortic
      valves.
AB  - BACKGROUND: Preoperative knowledge of the aortic annular diameter could enable
      the preoperative selection and preparation of an appropriately sized homograft
      aortic valve. OBJECTIVE: The aims of this study were to prospectively determine
      whether the combined use of transthoracic and multiplane transesophageal
      echocardiography allows accurate preoperative aortic annular measurements for the
      selection and preparation of adequately sized homograft aortic valves and to
      retrospectively evaluate the influence of the echocardiographic approach
      (transthoracic vs transesophageal) and the reader's level of experience on the
      accuracy of these measurements. METHODS: Aortic annular measurements were
      performed before the operation by an experienced reader who used a combination of
      transthoracic and multiplane transesophageal images of 25 patients (mean age 52
      +/- 13 years) referred for homograft aortic valve replacement. Measurements were
      also performed retrospectively by three additional readers with different levels
      of training in echocardiography. These readers acquired aortic annular diameters
      from prerecorded tapes and obtained measurements from each echocardiographic
      modality independently. All values were compared with the surgical measurement
      obtained with a ring valve sizer. RESULTS: With the combined echocardiographic
      approach, excellent agreement was found between preoperative echocardiographic
      and surgical measurements (mean difference +/- 2 standard deviations = 0.2 +/-
      1.4 mm). All echocardiographic data were found to be within 2 mm of the surgical
      measurement. These measurements were used to select and prepare the aortic
      homograft valve before insertion. The accuracy of annular measurements appeared
      to increase in parallel to the level of experience. The aortic annular
      measurements obtained retrospectively by a second experienced reader were more
      accurate with the use of transesophageal than with transthoracic echocardiography
      (p < 0.01). In contrast, the echocardiographic modality had no influence on the
      accuracy of measurements of less experienced readers (p > 0.2). CONCLUSIONS:
      Preoperative measurement of the aortic annular diameter by transthoracic and
      multiplane transesophageal echocardiography is accurate and clinically feasible.
      Preoperative knowledge of the aortic annular diameter may be used to select and
      prepare the aortic homograft, improving valve availability and reducing ischemic
      time.

PMID- 8873722
TI  - Detection of stroke during cardiac operations with somatosensory evoked
      responses.
AB  - OBJECTIVES: The objectives of this study were to determine if monitoring of
      intraoperative somatosensory evoked potentials could be used to detect stroke
      during cardiac operations and to establish indicators of cerebral ischemia based
      on changes in these potentials. METHODS: Twenty-five patients undergoing cardiac
      operations underwent preoperative and postoperative neurologic examinations as
      well as intraoperative recording of somatosensory evoked potentials. Detailed
      analysis of the waveforms of these potentials was performed. RESULTS: Two of the
      25 patients had intraoperative strokes. These patients and only these patients
      had changes in their somatosensory evoked potentials during the operation
      suggesting cerebral ischemia. The unilateral disappearance of the cortical
      somatosensory evoked potential waves correlated significantly with the clinical
      outcome of stroke (p < 0.004). Ischemic changes were detected in real time and
      were related to the removal of the aortic crossclamp in one patient and to the
      initiation of cardiopulmonary bypass in the other. CONCLUSIONS: Somatosensory
      evoked potentials can detect intraoperative stroke during cardiac operations.
      Acute, unilateral decreases in amplitude of the cortical potential are more
      useful than changes in latency in detecting intraoperative stroke.

PMID- 8873723
TI  - Extended aortic replacement for acute type A dissection with the tear in the
      descending aorta.
AB  - OBJECTIVE: There has been controversy as to the selection of surgical treatments
      for acute type A dissection with the tear in the descending thoracic aorta, a
      subtype of acute aortic dissection in which the limited tear is located distal to
      the left subclavian artery but the dissection extends retrogradely to the
      ascending aorta. METHODS: Total replacement of the ascending aorta and aortic
      arch was performed in 12 patients with acute type A dissection with the tear in
      the descending thoracic aorta between March 1991 and the end of September 1995.
      The indications for total replacement of the ascending aorta and aortic arch were
      cardiac tamponade, acute aortic regurgitation, cerebral ischemia, and dilatation
      of the ascending aorta. The operation was performed with the aid of
      extracorporeal circulation, blood cardioplegia, selective cerebral perfusion, and
      open distal anastomosis. The surgical procedure used was total replacement of the
      ascending aorta and aortic arch with a graft provided with three limbs
      accompanied by resection of the intimal tear in the descending thoracic aorta.
      RESULTS: Hospital death occurred in two patients (16.7%). In both, death was due
      to dissection/related complications of renal/mesenteric ischemia. The other 10
      patients have had uneventful postoperative courses over a mean period of 24
      months. CONCLUSIONS: Total replacement of the ascending aorta and aortic arch
      accompanied by resection of an intimal tear distal to the left subclavian artery
      seems to be justified in selected patients with acute type A dissection with the
      tear in the descending thoracic aorta.

PMID- 8873724
TI  - Development of an intraluminal device for the treatment of aortic regurgitation:
      prototype and in vitro testing system.
AB  - OBJECTIVES: Development of an intraluminal device to reduce aortic regurgitation
      could provide a strategy intermediate between medical treatment and aortic valve
      replacement. An initial prototype and a testing system have been designed.
      METHODS: Aortic valves obtained from heart transplant recipients were explanted
      and assessed in a mock circulatory loop with resistive and capacitive elements,
      including pressure-flow characteristics, similar to those of a normal arterial
      system. Normal heart function was simulated by a pulsatile ventricular-assist
      device. Pressure on each side of the valve and flow through the valve were
      recorded, allowing the calculation of regurgitant fractions and transvalvular
      gradients. Six solid geometrically differing obturators were tested. RESULTS: All
      six designs resulted in significant reduction in aortic regurgitation (p <
      0.0001), ranging from 15% to 38% improvement compared with control values. Small
      increases in transvalvular gradients (from 0 to 7 mm Hg) were also noted.
      DISCUSSION: Initial results suggest that an intraluminally placed obturator can
      reduce aortic regurgitation without creating clinically significant transvalvular
      gradients. These initial in vitro experiments demonstrate the feasibility of an
      intraluminal device for the treatment of aortic valve disease, and further
      investigation is warranted.

PMID- 8873725
TI  - Atrial flutter: a newly recognized complication of pediatric lung
      transplantation.
AB  - BACKGROUND AND METHODS: Atrial flutter after pediatric lung transplantation has
      not previously been reported. We reviewed the records of 78 children who
      underwent lung transplantation at our institution to characterize the incidence
      and clinical course of postoperative atrial flutter. The diagnosis was based on
      either a surface or transesophageal electrocardiogram that demonstrated a fixed
      cycle length atrial tachycardia that did not require ventricular participation.
      RESULTS: Atrial flutter occurred in seven of 62 (11.3%) patients who underwent
      bilateral sequential lung transplantation, zero of 10 patients after single lung
      transplantation, and zero of six patients after heart-lung transplantation. Ages
      of the patients with atrial flutter ranged from 2.5 months to 14 years.
      Electrocardiographic findings among patients varied with respect to p-wave
      morphology and atrioventricular conduction. No patient had a prior atrial
      arrhythmia or coexisting structural cardiac disease. None had atrial flutter in
      relation to a rejection episode. Two patients had atrial flutter transiently
      during the first postoperative day, but it resolved spontaneously. Five patients
      had recurrent atrial flutter that began 13 +/- 7 days after the operation. The
      mean cycle length of atrial flutter was 196 +/- 65 msec. The arrhythmia was
      unresponsive to digoxin in four patients to whom it was administered. It was
      controlled with procainamide in four patients and with flecainide in one. At 1
      and 6 months after lung transplantation, procainamide was discontinued in two
      patients without recurrence. One patient died of bronchiolitis obliterans 6
      months after the operation while still receiving flecainide. Two patients
      continue to receive procainamide 4 and 7 months after transplantation.
      CONCLUSIONS: (1) Atrial flutter commonly occurs after bilateral lung
      transplantation in children. (2) Electrocardiographic manifestations are
      variable. (3) Type 1 antiarrhythmic agents provide satisfactory control.

PMID- 8873726
TI  - Left-sided atrial flutter: characterization of a novel complication of pediatric
      lung transplantation in an acute canine model.
AB  - BACKGROUND: Postoperative atrial flutter has been observed in approximately 10%
      of children undergoing lung transplantation at our institution. We hypothesized
      that the left atrial anastomoses made to establish pulmonary venous continuity
      provide the primary electrophysiologic substrates for atrial flutter. OBJECTIVES:
      Our objectives were (1) to determine whether the left atrial suture lines alone
      are sufficient to produce atrial flutter in an acute canine model of lung
      transplantation and (2) to characterize any resulting reentrant circuits to
      surgically ablate the atrial flutter. METHODS: Supported by cardiopulmonary
      bypass, adult dogs (n = 10) underwent bilateral pneumonectomies. The left atrial
      anastomotic suture lines were simulated by dividing the tissue between the ostia
      of the transected superior and inferior pulmonary veins and closing the resulting
      defects. Bilateral suture lines were placed in group 1 (n = 6) to simulate
      bilateral lung transplantation. In group 2 (n = 4), only a left-sided suture line
      was placed to represent single lung transplantation. Unipolar 253-point biatrial
      endocardial mapping electrodes were inserted via bilateral ventriculotomies.
      Atrial flutter was induced by atrial burst pacing, and activation sequence maps
      were generated. In five of six cases in group 1, a T-incision connecting the two
      suture lines and the mitral anulus was then made. In group 2, a single incision
      from the suture line to the mitral anulus was performed in each case. Burst
      pacing was subsequently repeated. RESULTS: Atrial flutter could not be induced
      after bypass alone in any case. After simulated lung transplantation, sustained
      atrial flutter was reproducibly induced in 10 of 10 dogs. The mean cycle length
      in all dogs was 133 +/- 7 msec. There was no significant difference in mean cycle
      length or activation sequence patterns between groups 1 and 2. The reentrant
      circuit was confined to the left atrium. Each simulated left atrial anastomosis
      created a zone of conduction block around which circus movement could occur. In
      group 1, either suture line functioned as the central obstacle. Atrial flutter
      was terminated in five of five dogs in group 1 by means of the T-incision and in
      all four dogs in group 2 with the incision connecting the suture line to the
      mitral anulus. CONCLUSIONS: (1) In an acute canine model of lung transplantation,
      each left atrial suture line alone provides an electrophysiologic substrate for
      atrial flutter by creating a zone of conduction block around which circus
      movement can occur. (2) Extending this zone of block to the mitral anulus,
      together with interruption of the isthmus of tissue between the two suture lines
      present after bilateral lung transplantation, terminates the atrial flutter in
      this model and may have an application prophylactically at the time of lung
      transplantation in children to prevent postoperative atrial flutter.

PMID- 8873727
TI  - The influence of concordant xenografts on the humoral and cell-mediated immune
      responses to subsequent allografts in primates.
AB  - The humoral and cell-mediated immune responses to subsequent allografts were
      determined in primate recipients after concordant xenotransplantation as a bridge
      to allotransplantation. Heterotopic heart transplants (n = 4) were performed from
      cynomolgus monkeys into ABH type-matched olive baboons followed 2 weeks later by
      allotransplantation from ABH type-matched baboon donors. Allografts were
      explanted at 8 weeks. All recipients underwent splenectomy at the time of
      xenotransplantation and received immunosuppression with cyclosporine,
      azathioprine, and methylprednisolone. Concordant xenotransplantation in these
      primates did not induce humoral or cell-mediated immune responses that
      jeopardized subsequent allografts. The degree of xenospecific immune reactivity,
      as determined by specific cytotoxicity of recipient T-cell lines derived from the
      xenograft and extent of histologic xenograft rejection, did not predict the
      severity of subsequent allograft rejection. In two of the four recipients,
      xenotransplantation induced an alloreactive humoral response against antigens
      expressed by the B cells of more than 50% of members from a panel of 12 unrelated
      baboons. In all recipients, priming with xenogeneic splenocytes in vitro induced
      an accelerated proliferative T-cell response to allogeneic lymphocytes from 16%
      of this panel. This study affirms the role of concordant xenografts as
      appropriate biologic bridges to human allotransplantation. However, our results
      suggest that xenoreactive baboon memory CD4 T cells may recognize major
      histocompatibility complex class II--like structures shared between the
      xenogeneic and allogeneic targets. The potential allorecognition induced by a
      xenograft may affect the process of subsequent allograft donor selection.

PMID- 8873728
TI  - Amelioration of pulmonary allograft injury by administering a second rinse
      solution.
AB  - OBJECTIVE: The use of rinse solutions before reperfusing liver allografts has
      been shown to reduce cell death in rats. Carolina rinse solution (an
      extracellular solution that contains antioxidants, vasodilators, and other
      substrates that help prevent ischemia-reperfusion injury) has also been shown to
      improve liver function clinically in liver transplant recipients. This pilot
      study evaluates the value of a second pulmonary artery flush before reperfusion
      of a lung graft. METHODS: Six groups of Sprague-Dawley rats (n = 6 each) were
      subjected to the following: Group 1 lungs were preserved with modified Euro
      Collins solution followed by 24 hours of cold ischemia. Group 2 lungs were
      treated the same as group 1 but reperfused with blood. Group 3 lungs were
      preserved in Carolina rinse solution followed by 24 hours of cold ischemia. Group
      4 lungs were treated the same as group 3 lungs and then reperfused with blood.
      Lungs in groups 5 and 6 were preserved with Euro-Collins solution, stored cold
      for 24 hours, and then rinsed with Euro-Collins or Carolina rinse solution,
      respectively, before reperfusion with blood. Lungs were subsequently stained with
      trypan blue solution for 5 minutes. Lung blocks were fixed and embedded in water
      soluble methacrylate. Trypan blue--stained nuclei in nonviable endothelial cells
      and alveolar pneumocytes were counted in 10 different fields. RESULTS: Groups 1
      and 3, preserved with Euro-Collins and Carolina rinse solutions for 24 hours but
      not reperfused with blood, had significantly more viable endothelial cells
      (groups 1 and 3 vs group 2, p < 0.0001; group 3 vs group 4, p < 0.02) and
      pneumocytes (group 1 vs groups 2 and 4, group 3 versus group 2, p < 0.0001; group
      3 vs group 4; p < 0.035) than groups 2 and 4, which were subsequently reperfused
      with blood. Groups 5 and 6, which received a second rinse, also had significantly
      more viable endothelial cells (p < 0.0005) and pneumocytes (p < 0.0001) than
      control groups, which were not rinsed before reperfusion. CONCLUSIONS: We
      conclude that damage to pulmonary allografts resulting from prolonged ischemia is
      accentuated by reperfusion with blood. We also conclude that preservation with a
      single flush of Euro-Collins or Carolina rinse solution does not offer adequate
      protection, whereas a second rinse before reperfusion significantly decreases the
      number of damaged cells within the allograft.

PMID- 8873729
TI  - Inhibition of lipid peroxidation with the lazaroid U74500A attenuates ischemia
      reperfusion injury in a canine orthotopic heart transplantation model.
AB  - BACKGROUND: The lazaroid U74500A is a 21-aminosteroid that inhibits lipid
      peroxidation and attenuates ischemia-reperfusion injury. We examined the effect
      of U74500A on heart preservation with the use of a clinically relevant canine
      orthotopic heart transplantation model. METHODS AND RESULTS: Six donor dogs
      (group L) were pretreated intravenously with U74500A (10 mg/kg), and the dogs
      without pretreatment served as a control (group C, n = 6). The donor heart was
      preserved in cold University of Wisconsin solution for 24 hours. The heart was
      then transplanted orthotopically. Myocardial biopsy was performed to measure the
      adenosine triphosphate level at the end of ischemia. Before reperfusion,
      recipients in group L received another dose of U74500A (10 mg/kg) intravenously.
      After 3 hours of reperfusion, left ventricular function was evaluated by left
      ventricular pressure-volume relations with the use of a Millar catheter and
      conductance catheter, thereby deriving the slope of the end-systolic pressure
      volume relation, the slope of the stroke work-- end-diastolic volume relation,
      and the slope of the maximum dP/dt--end-diastolic volume relation. At the same
      time, serum creatine kinase MB isoenzyme and lipid peroxide levels were measured.
      The slopes of the end-systolic pressure-volume relation, the stroke work--end
      diastolic volume relation, and the maximum dP/dt--end-diastolic volume relation
      for group L were significantly higher than those for group C. The adenosine
      triphosphate levels for group L were significantly higher than those for group C.
      Serum creatine kinase MB isoenzyme and lipid peroxide levels for group L were
      significantly lower than those for group C. CONCLUSIONS: Inhibition of lipid
      peroxidation by the administration of U74500A was effective for 24-hour canine
      cardiac preservation. These results indicate that U74500A is a promising agent
      for heart allograft preservation.

PMID- 8873730
TI  - Cold ischemia-induced damage to vascular endothelium results in permeability
      alterations in transplanted lungs.
AB  - Despite suggestions of a connection between endothelial damage and permeability
      alterations after ischemia and reperfusion in pulmonary tissue undergoing
      transplantation, no direct correlation between vascular endothelial discontinuity
      and parenchymal edema has yet been shown. METHODS: Forty-two rat lungs were
      harvested and stored for 48 or 72 hours under hypothermic and ischemic
      conditions. Stored pulmonary tissue was studied before transplantation and 5
      minutes or 24 hours after transplantation by light microscopy and scanning
      electron microscopy of arterial vascular endothelium. RESULTS: Stored lungs not
      subjected to revascularization showed moderate perivascular edema, with small
      intercellular gaps in endothelial monolayers. Five minutes after transplantation,
      pulmonary tissue appeared congested, with perivascular and alveolar edema.
      Examination of vascular endothelium by scanning electron microscopy showed
      detachment of endothelial cells. Twenty-four hours after transplantation, edema,
      hemorrhage, and vascular congestion were found in all specimens. Arterial
      vascular endothelium showed weak intercellular connections, numerous
      intercellular gaps, and widespread cell detachment. Bronchial epithelial cells
      appeared damaged after storage, with loss of cilia, blebbing of apical cytoplasm,
      and cellular rounding. These changes were maintained 5 minutes after
      transplantation but appeared totally reversed after 24 hours in specimens stored
      48 hours, whereas bronchial denudation was observed in 72-hour stored lungs.
      Statistically significant positive correlations (Kendall p < 0.001) between
      revascularization time and alveolar edema and hemorrhage were found for both
      storage periods. CONCLUSION: The results from this study demonstrate correlation
      between loss of endothelial monolayer continuity and histologic evidence of
      vascular permeability increases in pulmonary tissue before and after lung
      transplantation.

PMID- 8873731
TI  - The effects of cardiopulmonary bypass temperature on neuropsychologic outcome
      after coronary artery operations: a prospective randomized trial.
AB  - The effect of systemic perfusion temperature on postoperative cognitive function
      was investigated in 96 adult patients undergoing elective coronary
      revascularization with cardiopulmonary bypass at 28 degrees C, 32 degrees C, or
      37 degrees C. Neuropsychologic performance was assessed 1 day before the
      operation and 6 weeks after the operation. Five tests were adapted from the
      Wechsler Adult Intelligence Scale and two from the Wechsler Memory Scale.
      RESULTS: No patients had major neurologic complications. Ninety-three patients
      completed the five Wechsler Adult Intelligence Scale tests, but only 70 went on
      to complete the Wechsler Memory Scale tests as well. In these, there was an
      effect of cardiopulmonary bypass temperature on the number of neuropsychologic
      tests in which there was a preoperative to postoperative deterioration (p =
      0.021), the number with bypass at 37 degrees C being significantly greater than
      the number with bypass at 32 degrees C (p = 0.015). Subsidiary analyses using a
      multivariate linear model examined the effect of cardiopulmonary bypass
      temperature on the magnitude of change, with or without allowing for other
      possible confounding influences. There was an adverse effect of normothermic (37
      degrees C) versus moderately hypothermic (32 degrees C) perfusion---more
      convincingly displayed in the analyses of all seven scores rather than just the
      Wechsler Adult Intelligence Scale scores. Further cooling to 28 degrees C
      conferred no additional benefit in terms of cognitive function. The importance of
      the deterioration is open to question.

PMID- 8873732
TI  - Angiographic and electron-beam computed tomography studies of retrograde
      cardioplegia via the coronary sinus.
AB  - Retroperfusion of the coronary sinus does not provide homogeneous distribution of
      cardioplegic solution. The goal of this study was to analyze the distribution of
      flow during retrograde cardioplegic infusion in cadaveric human hearts with two
      different techniques of coronary sinus cannulation: (1) internal occlusion of the
      coronary sinus by balloon inflation and (2) external occlusion by tightening the
      orifice of the coronary sinus around a simple catheter. To evaluate differences
      between the two techniques, angiographic and electron-beam computed tomographic
      studies were performed. Computed digital angiography was performed on 14 hearts.
      Angiographic patterns varied according to type of coronary sinus cannulation.
      With the balloon inflation technique, the marginal vein and the anterior
      descending vein were perfused first; the posterior descending vein was not
      perfused. This vein was opacified secondarily through a venovenous anastomosis
      located at the apex of the heart. Backward flow into the right atrium (steal
      phenomenon) was demonstrated. At completion of retroperfusion, the inferior part
      of the septum remained poorly opacified. Conversely, angiographic findings after
      external occlusion of the coronary sinus revealed simultaneous injection of all
      venous channels. The entire septum was well opacified at completion of
      retroperfusion. Electron-beam computed tomographic study was performed on eight
      hearts with the external occlusion technique and nine with the internal occlusion
      technique. The computed tomographic findings confirmed the results of digital
      angiography. The peak myocardial enhancement and the peak rising rate of
      myocardial enhancement within the interventricular septum were significantly more
      important (p < 0.0001) when the external coronary sinus occlusion mode was used
      than when the internal coronary sinus occlusion mode was used. In all hearts
      except one, the right ventricular wall was not opacified, regardless of the type
      of cannulation and the type of radiologic analysis. This study demonstrates the
      importance of coronary sinus cannulation technique in optimizing the protection
      of the interventricular septum with retrograde cardioplegic infusion.

PMID- 8873733
TI  - Coronary vascular regulation during postcardioplegia reperfusion.
AB  - BACKGROUND: This study extends previous investigations of global and regional
      myocardial blood flow during early postcardioplegia reperfusion. The hypothesis
      tested is that coronary vascular regulation becomes abnormal within 3 minutes
      after the start of postcardioplegia reperfusion. METHODS: Pigs (n = 40) were
      supported by cardiopulmonary bypass and 38 degrees C blood cardioplegic solution
      was infused. A control preischemic microsphere injection (No. 1) was given in
      asystolic hearts. Groups 1 to 3 had 1 hour of hypothermic cardioplegic arrest.
      Group 4 (control group) had 1 hour of perfusion without cardioplegia. A blood
      cardioplegic solution at 38 degrees C and 70 mm Hg pressure was infused to
      maintain asystole during the initial 7 to 10 minutes of reperfusion in all
      groups. Left ventricular intracavitary pressures were set at 0, 10, 20, or 0 mm
      Hg in groups 1, 2, 3, and 4 (n = 10 pigs per group), respectively, during the
      initial 7 minutes of reperfusion. The ventricle was then decompressed. At 30
      seconds, 3 minutes, and 6 minutes after reperfusion, microsphere injections 2, 3,
      and 4 were given in asystolic hearts. Microsphere injection No. 5 was given 10
      minutes after reperfusion in beating vented hearts. RESULTS: (1) Left ventricular
      distention during the initial 7 minutes of reperfusion after hypothermic
      cardioplegic arrest attenuates postischemic hyperemia. (2) Left ventricular
      intracavitary pressure of 20 mm Hg during reperfusion causes a decrease in
      endocardial blood flow relative to epicardial blood flow at 6 minutes after
      reperfusion. (3) Global myocardial blood flow during postcardioplegia reperfusion
      falls significantly below preischemic control values despite the return of
      electromechanical activity. INFERENCE: Coronary vascular regulation (i.e.,
      coronary resistance and metabolic flow recruitment) becomes abnormal within 3
      minutes after the start of reperfusion after hypothermic blood cardioplegic
      arrest.

PMID- 8873734
TI  - Direct effects of oxygenated crystalloid or blood cardioplegia on isolated
      myocyte contractile function.
AB  - The majority of myocardial protective techniques performed in the United States
      incorporate hypothermic, hyperkalemic blood or crystalloid cardioplegia.
      Oxygenated blood cardioplegia has not been compared with oxygenated crystalloid
      cardioplegia in an isolated myocyte model of hypothermic, hyperkalemic
      cardioplegic arrest in which direct measurements of contractile function and
      myocyte swelling can be made. Accordingly, isolated myocyte contractile function
      and myocyte profile surface area were examined after hypothermic arrest with
      oxygenated crystalloid or blood cardioplegia. METHODS: Isolated left ventricular
      pig myocytes were randomly assigned to undergo cardioplegic arrest for 2 hours at
      4 degrees C. Either oxygenated crystalloid or blood cardioplegia was used. After
      2 hours, myocytes were reperfused with standard cell medium at 37 degrees C and
      contractile function was examined. A control group of myocytes was maintained in
      cell medium at 37 degrees C for 2 hours. Myocyte velocity of shortening
      (micrometers per second) was examined at baseline and after beta-adrenergic
      stimulation (isoproterenol, 25 nmol/L). Velocity of shortening declined equally
      from baseline control values (65 +/- 2 micron n/sec) in the groups subjected to
      oxygenated crystalloid cardioplegia and blood cardioplegia (37 +/- 2 micron n/sec
      and 42 +/- 1 micron n/sec, respectively; p < 0.05). RESULTS: Although beta
      adrenergic stimulation caused a significant increase in velocity of shortening in
      all myocyte groups, the increase was less pronounced in myocytes subjected to
      crystalloid cardioplegia (157 +/- 6 micron n/sec) and blood cardioplegia (159 +/-
      6 micron n/sec) than in normothermic control myocytes (205 +/- microm/sec; p <
      0.05). Myocyte profile surface area, an index of cell volume, was measured in all
      myocyte groups. Myocyte surface area increased equally after cardioplegic arrest
      and rewarming in both cardioplegia groups (crystalloid 4119 +/- 53 micron2; blood
      3924 +/- 48 micron2); surface areas in both cardioplegia groups were
      significantly greater than in the normothermic control group (3158 +/- 39
      micron2, p < 0.05). CONCLUSION: Equivalent effects of oxygenated crystalloid and
      blood cardioplegia were observed with respect to myocyte contractile function,
      inotropic responsiveness, and intracellular volume regulatory processes.

PMID- 8873736
TI  - Aprotinin in primary valve replacement and reconstruction: a multicenter, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: Patients having cardiac operations often require blood transfusions.
      Aprotinin reduces the need for blood transfusions during coronary artery bypass
      graft operations. To determine the safety and effectiveness of aprotinin in
      reducing the use of allogeneic blood and postoperative mediastinal chest tube
      drainage, we studied 212 patients undergoing primary sternotomy for valve
      replacement or repair. METHODS: This study was multicenter, randomized,
      prospective, double-blind, and placebo-controlled. Patients received high-dose
      aprotinin (n = 71), low-dose aprotinin (n = 70), or placebo (n = 71). The study
      medication was given as a loading dose followed by a continuous infusion and pump
      prime dose. Heparin administration was standardized. Transfusions, postoperative
      mediastinal shed blood, and adverse events were tracked. RESULTS: Demographic
      profiles were similar among the treatment groups. Aprotinin did not decrease the
      percentage of patients receiving transfusions when compared with placebo (high
      dose aprotinin, 63%, p = 0.092; low-dose aprotinin, 52%, p = 0.592; placebo,
      48%). Aprotinin was associated with a reduction in the volume of mediastinal shed
      blood (high-dose aprotinin vs placebo, p = 0.002; low-dose aprotinin vs placebo,
      p = 0.017). Adverse events were equally distributed among the treatment groups
      except for postoperative renal dysfunction (high-dose aprotinin, 11%; low-dose
      aprotinin, 7%; placebo, 0%; p = 0.01). A disproportionate number of patients in
      the high-dose aprotinin group with postoperative renal dysfunction also had
      diabetes mellitus. CONCLUSIONS: Aprotinin treatment in this population did not
      reduce allogeneic blood use, although there were significant reductions in the
      volume of mediastinal shed blood.

PMID- 8873735
TI  - Cerebral protection during moderate hypothermic circulatory arrest:
      histopathology and magnetic resonance spectroscopy of brain energetics and
      intracellular pH in pigs.
AB  - OBJECTIVE: We evaluated the effect of antegrade and retrograde brain perfusion
      during moderate hypothermic circulatory arrest at 28 degrees C. METHODS:
      Phosphorus 31-magnetic resonance spectroscopy was used to follow brain energy
      metabolites and intracellular pH in pigs during 2 hours of ischemia and 1 hour of
      reperfusion. Histopathologic analysis of brain tissue fixed at the end of the
      experimental protocol was performed. Fourteen pigs were divided into two
      experimental groups subjected to antegrade (n = 6) or retrograde (n = 8) brain
      perfusion. Anesthesia (n = 8) and hypothermic cardiopulmonary bypass groups (15
      degrees C, n = 8) served as control subjects. In the antegrade and retrograde
      brain perfusion groups, the initial bypass flow rate was 60 to 100 ml x kg(-1) x
      min(-1). In the antegrade group, the brain was perfused through the carotid
      arteries at a flow rate of 180 to 210 ml x min(-1) during circulatory arrest at
      28 degrees C. In the retrograde group, the brain was perfused through the
      superior vena cava at a flow rate of 300 to 500 ml x min(-1) during circulatory
      arrest at 28 degrees C. RESULTS: The intracellular pH was 7.1 +/- 0.1 and 7.2 +/-
      0.1 in the anesthesia and hypothermic bypass groups, respectively. Brain
      intracellular pH and high-energy metabolites (adenosine triphosphate,
      phosphocreatine) did not change during the course of the 3.5-hour study. In the
      antegrade group, adenosine triphosphate and intracellular pH were unchanged
      throughout the protocol. In the retrograde perfusion group, the intracellular pH
      level decreased to 6.4 +/- 0.1, and adenosine triphosphate and phosphocreatine
      levels decreased within the first 30 minutes of circulatory arrest and remained
      at low levels until the end of reperfusion. High-energy phosphates did not return
      to their initial levels during reperfusion. Histopathologic analysis of nine
      regions of the brain showed good preservation of cell structure in the
      anesthesia, hypothermic bypass, and antegrade perfusion groups. The retrograde
      perfusion group showed changes in all the regions examined. CONCLUSIONS: The
      study shows that moderate hypothermic circulatory arrest at 28 degrees C with
      antegrade brain perfusion during circulatory arrest protects the brain but that
      retrograde cerebral perfusion at 28 degrees C does not protect the brain.

PMID- 8873737
TI  - Activation of coagulation and fibrinolytic pathways in patients with left
      ventricular assist devices.
AB  - Left ventricular assist devices have provided successful supportive therapy for
      patients awaiting cardiac transplantation for extended periods of time. Although
      thromboembolic events have complicated support with these devices, the HeartMate
      left ventricular assist device developed by Thermo Cardiosystems, Inc., Woburn,
      Massachusetts, was specifically designed with a textured blood-contacting surface
      to minimize this risk. Clinical experience with this device has been encouraging,
      inasmuch as minimal thromboembolic complications have occurred despite the
      absence of anticoagulation. The coagulation and fibrinolytic pathways in these
      individuals were investigated to better understand the hematologic status of
      patients treated with the Thermo Cardiosystems device. Despite apparently normal
      prothrombin and activated partial thromboplastin times, as well as platelet
      counts, evidence of significant thrombin generation and fibrinolysis was present.
      To eliminate underlying cardiac failure as the responsible factor for these
      abnormalities, we made similar measurements in patients with end-stage heart
      failure who were not supported by an assist device or anticoagulation. These
      measurements revealed no evidence of thrombin generation or fibrinolysis. These
      data demonstrate that patients supported with a left ventricular assist device,
      while successfully sustained without systemic anticoagulation, nevertheless have
      evidence of activation of coagulation. These phenomena appear to be related to
      the presence of the device rather than to the underlying cardiac abnormalities.
      Although procoagulant and fibrinolytic pathways are apparently balanced in these
      patients, these data underscore the potential for the development of bleeding or
      thrombosis in clinically relevant settings.

PMID- 8873738
TI  - Reduction of bleeding after heart operations through the prophylactic use of
      epsilon-aminocaproic acid.
AB  - Excessive postoperative bleeding after heart operations continues to be a source
      of morbidity. This prospective double-blind study evaluated epsilon-aminocaproic
      acid as an agent to reduce postoperative bleeding and investigated its mode of
      action. One hundred three patients were randomly assigned to receive either 30 gm
      epsilon-aminocaproic acid (51 patients) or an equivalent volume of placebo (52
      patients). In a subset of these patients (14 epsilon-aminocaproic acid, 12
      placebo), tests of platelet function and fibrinolysis were performed. RESULTS: By
      multivariate analysis, three factors were associated with decreased blood loss in
      the first 24 hours after operation: epsilon-aminocaproic acid versus placebo (647
      ml versus 839 ml, p = 0.004), surgeon 1 versus all other surgeons (582 ml versus
      978 ml, p = 0.002), and no intraaortic balloon versus intraaortic balloon pump
      use (664 ml versus 1410 ml, p = 0.02). No significant differences in platelet
      function could be demonstrated between the two groups. Inhibited fibrinolysis, as
      reflected by less depression of the euglobulin clot lysis and no rise in D-dimer
      levels, was significant in the epsilon-aminocaproic acid group compared with the
      placebo group. CONCLUSION: The intraoperative use of epsilon-aminocaproic acid
      reduces postoperative cardiac surgical bleeding.

PMID- 8873739
TI  - Video-assisted thoracoscopic surgery in patients previously treated for
      intrathoracic lymphoma.

PMID- 8873740
TI  - Native cardiectomy in a heterotopic heart transplant recipient.

PMID- 8873741
TI  - Clinical endovascular placement of branched graft for type B aortic dissection.

PMID- 8873742
TI  - An adjustable, percutaneously placed helical coil: control of left ventricular
      filling pressure during cardiopulmonary bypass in severe left ventricular
      failure.

PMID- 8873743
TI  - Closure with bronchial wall flap and omental pedicle of defect caused by
      dehiscence of tracheal suture line after extended right upper sleeve lobectomy.

PMID- 8873744
TI  - Pericardial patch augmentation of the tissue-deficient mitral valve in common
      atrioventricular canal.

PMID- 8873745
TI  - Isolated primary chylopericardium: treatment by thoracoscopic thoracic duct
      ligation and pericardial fenestration.

PMID- 8873746
TI  - Primary sarcoma of pulmonary artery and valve: multimodality treatment by
      chemotherapy and homograft replacement.

PMID- 8873747
TI  - Salvage resection of a chemorefractory mediastinal germ cell tumor.

PMID- 8873748
TI  - Interleukin-10 concentration in children undergoing cardiopulmonary bypass.

PMID- 8873749
TI  - Atrial natriuretic peptide release after cardiac transplantation.

PMID- 8873750
TI  - Gap junction formation between cultured embryonic lens cells is inhibited by
      antibody to N-cadherin.
AB  - Intercellular communication mediated by gap junctions is important for tissue
      homeostasis in the avascular lens, and extensive areas of gap junctions form
      between fiber cells during fiber cell differentiation and lens development. We
      examined the role of the calcium-dependent cell adhesion molecule, N-cadherin, in
      the process of gap junction formation between fiber cells. Lentoids,
      multicellular structures with characteristics of differentiated fiber cells, were
      isolated from embryonic chick lens cultures and subsequently paired to provide an
      in vitro model of fiber cell interactions. Gap junction formation between cells
      of paired lentoids was monitored by observing the lentoid-to-lentoid transfer of
      fluorescent dyes, either calcein or Lucifer yellow, over a time course of up to
      48 hr. Dye transfer between lentoids was inhibited upon the addition to the
      medium of Fab fragments (100-622 microgram/ml) of a monoclonal antibody specific
      for N-cadherin, and also by the reduction of extracellular calcium in the
      incubation medium. However, the addition of Fab fragments (100-1500 microgram/ml)
      of an antibody to a fiber-cell-specific integral membrane protein, MIP, did not
      change the time course nor extent of dye transfer between lentoids. Our results,
      using cultured embryonic cells, extend those from previous studies with cell
      lines and transfected cells. We conclude that cadherin interactions facilitate
      the formation of gap junctions between embryonic lens fiber cells, by the
      stabilization of membrane appositions and/or by the generation of an
      intracellular signal(s).

PMID- 8873751
TI  - The role of localized cell surface-associated glycoproteins during fertilization
      in the hydrozoan Aequorea.
AB  - Hydrozoan eggs can be fertilized only at the site of polar body formation and
      first acquire this ability during second polar body formation. The eggs of
      Aequorea victoria form a discrete Triticum lectin binding moiety in the jelly
      coat near the first polar body as it is being given off and also a discrete
      concanavalin A binding moiety associated with the egg surface where the second
      polar body forms, which disappears immediately after fertilization. The germinal
      vesicle has an eccentric position in full grown Aequorea oocytes. The region of
      oocyte surface closest to the germinal vesicle is the site where the polar bodies
      normally form. When oocytes are centrifuged during oocyte maturation, the meiotic
      apparatus sometimes shifts to a different position with reference to the egg
      surface and polar bodies are given off at this new site. There is a corresponding
      shift in the position of the Triticum and concanavalin A lectin binding moieties,
      indicating that their formation is associated with local events occurring at the
      site of polar body formation. Treatment of Aequorea eggs with Triticum or
      concanavalin A causes a marked reduction in the ability of these eggs to be
      fertilized, suggesting that sugar-containing moieties, to which the lectins bind,
      play a role in fertilization. Removal of sugars on these moieties with
      mannosidase or N-acetylglucosaminidase, or the cleavage of the protein the sugars
      are attached to with trypsin, results in eggs that do not bind Triticum or
      concanavalin A and also show a marked reduction in the ability to be fertilized.
      These experiments suggest that the lectin binding moieties are glycoproteins.

PMID- 8873752
TI  - cAMP-dependent protein kinase is required for the expression of a gene
      specifically expressed in Dictyostelium prestalk cells.
AB  - In the Dictyostelium slug there are two types of prestalk cells, pstA cells and
      pstO cells, that differ in their ability to utilize the distal and proximal parts
      of the promoter of ecmA, a gene that is specifically expressed in prestalk cells.
      When Rm, a dominant inhibitory form of the regulatory subunit of cAMP-dependent
      protein kinase (PKA), is expressed under the control of the complete promoter of
      the ecmA gene (in a construct termed ecmAO:Rm) development proceeds to the slug
      stage. Although able to form small but outwardly normal slugs, ecmAO:Rm cells are
      defective in prestalk cell differentiation. In ecmAO:Rm cells, the induction of
      pstA- and pstO-specific gene expression by the stalk cell inducer DIF is greatly
      inhibited. Paradoxically, a very large fraction of the cells in an ecmAO:Rm slug
      show evidence of once having expressed the ecmA and ecmO prestalk markers.
      However, we present evidence that this is due to abortive prestalk cell
      differentiation that terminates when sufficient Rm protein has accumulated to
      block PKA activity. This results in regulative transdifferentiation of prespore
      cells to form prestalk cells. During their transitory period as prestalk cells
      the ecmAO:Rm cells coexpress both the ecmA and ecmO markers, indicating a
      possible link between PKA activity and divergence of the two prestalk cell
      subtypes. Finally, we show that the level of the DNA binding activity believed to
      lie at the end of the DIF signal transduction pathway is reduced in ecmAO:Rm
      slugs.

PMID- 8873753
TI  - The embryonic central nervous system lineages of Drosophila melanogaster. I.
      Neuroblast lineages derived from the ventral half of the neuroectoderm.
AB  - Central nervous system development in Drosophila starts with the delamination
      from the neuroectoderm of about 30 neuroblasts (NBs) per hemisegment.
      Understanding the mechanisms leading to the specification of the individual NBs
      and their progeny requires the identification of their lineages. Here we describe
      17 embryonic NB lineages derived from the ventral half of the neuroectoderm and
      we assign these lineages to identified medial and intermediate NBs. The lineages
      are composed of interneurons (NB 1-2, NB 2-1, MP2, NB 4-1, NB 5-1, NB 5-3, NB 6
      1, NB 6-2, and NB 7-2), interneurons and motoneurons (NB 3-1, NB 3-2, NB 4-2, NB
      5-2, NB 7-1, and NB 7-3), or interneurons, motoneurons, and glial cells (NB 1-1
      and NB 2-2). NB 1-1, NB 2-2, and NB 3-1 form segment-specific lineages.
      Neuroectodermal progenitors forming NB 2-1, NB 5-1, and NB 7-3 divide while still
      in the ectoderm to give rise to an additional epidermoblast. Expression of
      segmentation genes is not lineal in the clones of NB 1-2 and NB 7-3 (engrailed),
      NB 1-1, NB 4-2, and NB 7-1 (even-skipped), and NB 7-1 (gooseberry-proximal). The
      timing of delamination for individual NBs as well as the number of their progeny
      is not strictly invariant. The 17 NBs produce about 200 neurons and only three
      glial cells, corresponding to about 70% of the estimated total number of neurons
      and 10% of the glial cells per thoracic and abdominal hemisegment. Previously
      identified neural cell types were linked to particular lineages and we introduce
      a systematic terminology for the ventral nerve cord neurons. The wild-type clones
      provide a foundation for the analysis of mutants, expression patterns, and
      experimental manipulations.

PMID- 8873754
TI  - daughterless is required for Drosophila photoreceptor cell determination, eye
      morphogenesis, and cell cycle progression.
AB  - Initiation of Drosophila peripheral nervous system (PNS) development requires the
      achaete-scute complex (AS-C) and the atonal (ato) genes. The AS-C and ato encode
      basic helix-loop-helix (bHLH) transcription factors that dimerize in vitro with
      another bHLH protein, daughterless (da). da has many functions during Drosophila
      embryonic development, as it is required for proper sex determination, oogenesis,
      and neurogenesis. Here, we examine the expression and function of da within the
      developing Drosophila eye. The use of a monoclonal antibody to the Da protein
      revealed that Da levels are modulated across the developing eye disc. Within the
      morphogenetic furrow (MF) and photoreceptor cell R8, there is a cell-by-cell
      correspondence between high levels of Da protein expression and Ato protein
      expression. Mosaic analysis of adult tissue demonstrates that da function is cell
      autonomous and required within R2, R3, R4, R5, and R8. Examination of gene
      expression in da- imaginal disc clones reveals that da regulates Ato expression
      in the MF, affects the progression of the MF, and is necessary for the
      reestablishment of the G2 and M phases of the synchronized cell cycle posterior
      to the MF.

PMID- 8873755
TI  - Transforming growth factor-beta is a survival factor for neonate cortical
      neurons: coincident expression of type I receptors in developing cerebral
      cortices.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide which
      plays a crucial role in the regulation of cell proliferation, differentiation,
      and organogenesis. In the present study, we investigated the expression of
      signaling receptors for TGF-beta in developing mice by in situ hybridization,
      revealing a significant difference in the expression of TGF-beta type I and type
      II receptors. Unexpectedly, the TGF-beta type I receptors were exclusively
      expressed without any detectable expression of the TGF-beta type II receptors in
      developing cerebral cortices. In primary cortical neurons, a neutralizing
      antibody for TGF-beta significantly reduced the expression of bcl-2 and
      subsequently induced neuronal cell death, indicating that TGF-beta functions as a
      survival factor for cortical neurons in vitro. Consistent with the result of in
      situ hybridization, the TGF-beta, type I but not type II receptors were detected
      in primary cortical neurons by affinity crosslink and RT-PCR analyses. The
      concomitant expression of TGF-beta2 and the TGF-beta type I receptors in
      developing cerebral cortices suggests that the TGF-beta signaling system plays a
      pivotal role in neuronal differentiation and that unidentified components may be
      involved in TGF-beta signaling in the development of the central nervous system.

PMID- 8873756
TI  - Inhibition of cranial neural crest adhesion in vitro and migration in vivo using
      integrin antisense oligonucleotides.
AB  - Although it is well-established that beta1 integrins play a functional role in
      the migration of cranial neural crest cells, little is known about the number or
      importance of their associated alpha subunits. Here, we have utilized antisense
      oligonucleotides (aONs) against various mammalian integrin alpha subunits to
      functionally "knock out" integrins in vitro and in vivo. First, we examined the
      attachment in vitro of cranial neural crest cells to fibronectin and laminin in
      the presence of antisense or reversed-sense oligonucleotides using a quantitative
      adhesion assay. We found three alpha integrin aONs that blocked attachment to
      fibronectin substrates only, one that blocked attachment to laminin substrates
      only, and one that blocked attachment to both fibronectin and laminin. As
      expected, an aON to chick beta1 integrin reduced attachment to both fibronectin
      and laminin substrates. These results suggest that there are three or more
      functionally distinct integrin heterodimers on avian cranial neural crest cells.
      Second, we examined the ability of aONs against various alpha integrin subunits
      to perturb cranial neural crest migration in vivo by injecting the
      oligonucleotides into the cranial mesenchyme through which neural crest cells
      migrate. Those alpha aONs that inhibited cell attachment in vitro also caused
      neural crest and/or neural tube abnormalities after injection in vivo. In
      addition, two aONs that had no effect in vitro did affect emigration of neural
      crest cells in vivo. Immunoprecipitations revealed that some integrin subunits
      were depleted after treatment with antisense but not reversed-sense
      oligonucleotides both in vivo and in vitro. The results suggest that integrin
      alpha subunits are required for cranial neural crest cell attachment and
      emigration.

PMID- 8873757
TI  - The cellular patterns of BDNF and trkB expression suggest multiple roles for BDNF
      during Xenopus visual system development.
AB  - The temporal patterns of BDNF and trkB expression in the developing Xenopus
      laevis tadpole, and the responsiveness of retinal ganglion cells to BDNF, both in
      culture and in vivo, suggest significant roles for this neurotrophin during
      visual system development (Cohen-Cory and Fraser, Neuron 12, 747-761, 1994;
      Nature 378, 192-196, 1995). To examine the potential roles of this neurotrophin
      within the developing retina and in its target tissue, the optic tectum, we
      studied the cellular sites of BDNF expression by in situ hybridization. In the
      developing optic tectum, discrete groups of cells juxtaposed to the tectal
      neuropil where retinal axons arborize expressed BDNF, supporting the target
      derived role commonly proposed for this neurotrophin. In the retina, retinal
      ganglion cells, ciliary margin cells, and a subset of cells in the inner nuclear
      layer expressed the BDNF gene. The expression of BDNF coincided with specific
      trkB expression by both retinal ganglion cells and amacrine cells, as well as
      with the localization of functional BDNF binding sites within the developing
      retina, as shown by in situ hybridization and BDNF cross-linking studies. To test
      for a possible role of endogenous retinal BDNF during development, we studied the
      effects of neutralizing antibodies to BDNF on the survival of retinal ganglion
      cells in culture. Exogenously administered BDNF increased survival, whereas
      neutralizing antibodies to BDNF significantly reduced baseline retinal ganglion
      cell survival and differentiation. This suggests the presence of an endogenous
      retinal source of neurotrophic support and that this is most likely BDNF itself.
      The retinal cellular patterns of BDNF and trkB expression as well as the effects
      of neutralizing antibodies to this neurotrophin suggest that, in addition to a
      target-derived role, BDNF plays both autocrine and/or paracrine roles during
      visual system development.

PMID- 8873758
TI  - lem7, a novel temperature-sensitive Arabidopsis mutation that reversibly inhibits
      vegetative development.
AB  - An important question in developmental biology concerns the mechanisms by which a
      few cells coordinate division and differentiation to yield the complex structures
      and organs found in multicellular organisms. During vegetative growth in plants,
      cells in the apical meristem must coordinate division and differentiation to
      yield the fully mature leaf organ. Alterations in these processes may result in
      an abnormal leaf. In this paper we present the isolation and characterization of
      an EMS-generated, cold-temperature-sensitive mutation in Arabidopsis thaliana,
      designated lem7 (leaf morphogenesis). lem7 is a semidominant mutation that maps
      to a novel locus on chromosome 2. When grown at 16 degrees C, lem7 reversibly
      arrests leaf development at the shoot apex. In contrast, lem7 grown at 30 degrees
      C appears phenotypically normal. Our data also suggest that the Lem7 locus may
      not be involved solely in leaf organogenesis, but may also play a role in floral
      development and the maintenance of patterns and structures after cellular
      differentiation. At an intermediate temperature of 23 degrees C, leaves on the
      lem7 plant emerged phenotypically normal but began to show drastic changes at
      about 13 days postgermination. These changes include a reduced bilateral
      symmetry, a rough leaf lamina, a reduced number of trichomes, and an altered
      vascular network. Leaves that developed at the permissive temperature (30 degrees
      C) and shifted to the nonpermissive temperature (16 degrees C) form tumor-like
      outgrowths. Histological analysis of these tumor-like outgrowths and leaves grown
      at the intermediate temperature reveal abnormally large mesophyll cells, a
      disorganized mesophyll layer, and collapsed epidermal cells. We propose that the
      reversible inhibition of leaf development in lem7 under nonpermissive
      temperatures may serve as a useful tool for identifying genes involved in
      Arabidopsis leaf organogenesis.

PMID- 8873759
TI  - Nonmyristoylated MARCKS complements some but not all of the developmental defects
      associated with MARCKS deficiency in mice.
AB  - The myristoylated alanine-rich C kinase substrate, or MARCKS protein, is a widely
      expressed, prominent substrate for protein kinase C. Although the exact function
      of MARCKS has not been elucidated, targeted disruption of the MARCKS gene (Macs)
      in mice has shown that MARCKS plays a crucial role in the development of the
      central nervous system. Mice deficient in MARCKS exhibited universal perinatal
      death with defects in neurulation, fusion of the cerebral hemispheres, formation
      of the great forebrain commissures, and retinal and cortical lamination (Stumpo
      et al., Proc. Natl. Acad. Sci. USA 92, 944-948, 1995). In the present studies, a
      transgene consisting of approximately 3.4 kb of promoter from the human MARCKS
      gene (MACS), with an epitope tag sequence inserted at the carboxyl terminus of
      the MARCKS coding region, was able to complement completely MARCKS deficiency in
      mice. Thus, the human transgene contained all of the elements necessary for
      normal developmental expression of MARCKS. To test the importance of MARCKS
      myristoylation to its developmental role, an otherwise identical transgene was
      constructed in which the glycine at the amino terminus of MARCKS was mutated to
      an alanine. This mutation, which resulted in the expression of nonmyristoylated
      MARCKS, was successful in partially rescuing the Macs null phenotype.
      Specifically, about 25% of these mice survived the perinatal period; these
      survivors appeared to develop normally except for slightly decreased body size.
      In both the survivors and the nonsurvivors, all of the known anatomical defects
      associated with MARCKS deficiency were corrected by expression of the
      nonmyristoylated human protein. These results indicate that myristoylation of
      MARCKS is not required for the protein to correct many of the developmental
      abnormalities characteristic of its deficiency.

PMID- 8873760
TI  - Alternative splicing of the Endo16 transcript produces differentially expressed
      mRNAs during sea urchin gastrulation.
AB  - The Endo16 gene codes for an RGD-containing calcium-binding protein that is found
      on the basal surfaces and in the extracellular matrix of cells of the
      invaginating archenteron during sea urchin gastrulation. Previously, we have
      shown that Endo16 is a single copy gene and we have determined the coding
      sequence and analyzed the temporal and spatial expression of a 6.6-kb mRNA. In
      this report we demonstrate that two additional longer Endo16 mRNAs are produced
      by differential splicing rather than alternative promoter usage. cDNA clones for
      two 8.5-kb mRNAs have been isolated and analyzed. The two 8.5-kb mRNAs are
      identical to each other in the coding region and differ only in their 3' UTRs.
      The extended open reading frame of the 8.5-kb mRNAs code for domains already
      identified in the 6.6-kb mRNA, including two different types of calcium-binding
      motifs and a region with a highly conserved cysteine pattern similar to that
      found in Ecm1 in the mouse. The 6.6- and 8.5-kb mRNAs show overlapping but
      distinct temporal as well as spatial expression patterns during gastrulation.

PMID- 8873761
TI  - Patterns of distal-less gene expression and inductive interactions in the head of
      the direct developing frog Eleutherodactylus coqui.
AB  - The direct developing frog Eleutherodactylus coqui exhibits radical changes in
      its embryogenesis. A frog-like head forms directly with no appearance of a cement
      gland or several jaw cartilages characteristic of tadpoles, and limbs appear
      early in development. The numerous differences in the embryogenesis of E. coqui
      provide an opportunity to examine developmental causes for the evolutionary shift
      from biphasic to direct development. We have cloned DNA fragments corresponding
      to four E. coqui genes related to the Drosophila distal-less gene Dll. While the
      expression patterns of the distal-less genes are generally conserved, there are
      some spatiotemporal differences when embryos of E. coqui are compared to those of
      Xenopus laevis. The changes in gene expression are correlated with the embryonic
      changes in head structures including craniofacial cartilages and in particular,
      the cement gland. We have then examined inductive interactions involved in cement
      gland formation by interspecific transplants and recombinants. E. coqui embryos
      can generate signaling that culminates in cement gland formation, but E. coqui
      ectoderm appears to be incapable of a cement gland response. These results show
      here that inductive interactions in the anterior region of the E. coqui embryo
      have been modified during the evolution of direct development, and that changes
      in the competence of the E. coqui ectoderm may be responsible for the loss of
      certain tadpole-specific structures, such as cement gland.

PMID- 8873762
TI  - RNA transport to the vegetal cortex of Xenopus oocytes.
AB  - Xcat-2 RNA, a component of the germ plasm in Xenopus, localizes with the
      mitochondrial cloud material to the vegetal cortex in stage II oocytes. Vg1 RNA
      also localizes to the vegetal cortex, but later in stage III/IV oocytes, using a
      microtubule dependent pathway. To further analyze the mechanisms involved in RNA
      transport, in situ hybridization and autoradiography were used to follow the
      localization of endogenous Vg1 and injected Xcat-2 transcripts in stage IV
      oocytes. We show that Xcat-2 is competent to localize to the vegetal cortex quite
      independently of the mitochondrial cloud. Xcat-2 RNA appears to use the late Vg1
      localization pathway, as depolymerization of microtubules by cold or nocodazole
      treatment prevented translocation of Xcat-2 transcripts, but did not result in
      the disruption of Xcat-2 anchored in the cortex. Furthermore, RNA transport was
      shown to be stage dependent for both Vg1 and Xcat-2 RNAs, as they did not
      localize in fully grown stage VI oocytes after injection. RNA sequences both
      required and sufficient to direct Xcat-2 to the vegetal cortex were mapped to a
      sequence of 150 nt immediately adjacent to the open reading frame and additional
      sequences at the end of the 3' untranslated region. Mapping was accomplished by
      injecting deletion mutant transcripts into stage IV oocytes and monitoring
      localization by RNase protection and autoradiography. All mutants competent for
      translocation were also capable of cortical anchoring, suggesting that the same
      signal is used for both steps. We speculate that two separate RNA pathways
      evolved during the course of Xenopus oogenesis. One pathway, specialized for the
      transport of germ plasm by way of the mitochondrial cloud, occurs early to ensure
      the segregation of the germ cell lineage. The other, late, pathway may serve as
      the more general transport system for localizing RNAs involved in somatic cell
      differentiation.

PMID- 8873763
TI  - Differentiation of embryonal stem cells into keratinocytes: comparison of wild
      type and beta 1 integrin-deficient cells.
AB  - beta 1 Integrins are known to regulate terminal differentiation and morphogenesis
      in the adult epidermis. We have investigated their role in the embryonic
      development of keratinocytes by comparing the differentiation of wild-type and
      beta 1-null mouse embryonal stem (ES) cells. By 12-15 days in culture,
      differentiation of embryonic or simple epithelial cells occurred in both ES cell
      populations, as detected by expression of keratins 8, 18, and 19. From 21 days,
      expression of keratins 10 and 14 and of the cornified envelope precursor
      involucrin indicated that some of the wild-type cells had differentiated into
      keratinocytes. In contrast, keratinocyte markers were not expressed in beta 1
      null cultures. The beta 1-null cells failed to express the alpha 2 and alpha 3
      integrin subunits on the cell surface, consistent with the association of these a
      subunits with beta 1. Furthermore, alpha 6 and beta 4 expression was reduced in
      the beta 1-null cultures. Although beta 1-null ES cells failed to undergo
      differentiation into keratinocytes in vitro, they did form keratinocyte cysts
      expressing alpha 6 beta 4, keratins 1 and 14, and involucrin when allowed to form
      teratomas by subcutaneous injection in mice; furthermore, beta 1-null
      keratinocytes were found in the epidermis of a wild-type/beta 1-null chimeric
      mouse. As judged by immunofluorescence microscopy, extracellular matrix assembly
      was severely impaired in beta 1-null ES cell cultures, but not in the teratomas
      or chimeric mouse skin. We therefore speculate that the failure of beta 1-null
      cells to differentiate into keratinocytes in vitro may reflect an inability to
      assemble a basement membrane.

PMID- 8873764
TI  - Effects of intermediate filament disruption on the early development of the
      peripheral nervous system of Xenopus laevis.
AB  - The principal function of intermediate filaments is to strengthen cells. Their
      developmentally regulated, tissue-specific patterns of expression further suggest
      that they modulate cellular structural properties during development. To explore
      the role of intermediate filaments in development, we injected RNA encoding a
      truncated form of the Xenopus laevis middle-molecular-weight neurofilament
      protein (NF-M) into embryonic frog blastomeres at the 2-cell stage. A similar
      truncated form of mammalian NF-M disrupts neurofilaments (Type IV) and vimentin
      (Type III) intermediate filaments in transfected fibroblasts. In cultures made
      from dissociated neural tubes and their adjacent myotomes, the resultant protein
      disrupted both desmin filaments in muscle cells and neurofilaments in neurons
      during the first day of culture, which corresponds to stage 35/36 in the intact
      embryo. We next examined the effects of this truncated neurofilament protein on
      development of the nervous system. The greatest effects were seen on development
      of cranial and primary motor nerves, which were severely stunted as late as stage
      37/38. In addition to these effects, ectopic neurons also appeared immediately
      beneath the epidermis along the flank of tadpoles expressing the truncated
      neurofilament protein. Whereas the former effects on peripheral nerve development
      were nearly identical to effects obtained with injected neurofilament antibodies,
      the ectopic neurons were novel, suggesting they resulted from the disruption of
      intermediate filaments other than the neurofilaments. These experiments thus
      implicate intermediate filaments in several functions important for normal neural
      development.

PMID- 8873765
TI  - Specific muscle contacts induce increased transmitter release and neuritic
      arborization in motoneuronal cultures.
AB  - Identified buccal motoneuron 19 (B19), isolated from the nervous system of
      Helisoma and plated into cell culture, is selective in synapse formation and
      requires contact with appropriate muscle targets before acquiring secretory
      competence. Action potential-regulated transmitter release was elevated
      specifically at neuritic arbors in contact with appropriate muscle fibers. In
      contrast, contact between B19 and inappropriate muscle targets failed to induce
      changes in presynaptic secretory properties. Spontaneous transmitter release rate
      was elevated globally across neuritic arbors of B19 in appropriate muscle
      cocultures, including arbors without direct muscle contact. In addition, dual
      contacts formed between B19 and two different muscle targets resulted in
      significant elevations in excitation-secretion coupling only at neuritic sites of
      appropriate muscle contact and not at sites of contact with mismatched targets.
      Image analyses of presynaptic neuronal architecture revealed that appropriate,
      but not novel, muscle targets elicited increased arborization of neurites at
      sites of neuron-muscle contact. In contrast to results with neuron B19, secretory
      properties of buccal neuron 5 (B5), a neuron capable of forming inappropriate
      chemical synapses with a number of novel targets in culture, were not enhanced by
      inappropriate muscle contact. We conclude that muscle targets vary in their
      ability to induce presynaptic modifications (e.g., excitation-secretion coupling,
      spontaneous transmitter release, and neuritic arborization) in identified
      motoneurons of Helisoma. These results imply that separate molecular pathways
      exist which control each of these events during synaptic differentiation. The
      differential potency of muscle targets for induction of presynaptic changes
      indicates the existence of a cellular mechanism of target recognition. We
      hypothesize that such a mechanism underlies the ability of neuron B19 to
      discriminate between potential postsynaptic partners in cell culture.

PMID- 8873766
TI  - Maturation of the acetylcholine receptor in skeletal muscle: regulation of the
      AChR gamma-to-epsilon switch.
AB  - During the development of the mammalian neuromuscular junction, acetylcholine
      receptors (AChRs) become localized to the postsynaptic muscle membrane. As this
      process nears completion, the fetal form of the receptor, containing a gamma
      subunit (composition alpha 2 beta gamma delta) is gradually replaced by an
      epsilon subunit-containing adult form (alpha 2 beta epsilon delta). To understand
      how this transition is controlled, we compared the expression and regulation of
      the AChR gamma and epsilon subunits in developing, adult, and cultured muscles.
      Immunostaining with subunit-specific antibodies showed that replacement of gamma
      subunit- by epsilon subunit-containing AChRs occurs largely during the first
      postnatal week in fast-twitch muscles, and occurs homogeneously throughout
      individual endplates. In the slow-twitch soleus, however, this transition is
      delayed, and in the multiply innervated slow fibers of extraocular muscle, gamma
      subunit expression persists into adulthood. The transcriptional bases of the AChR
      subunit transition, and of these intermuscular variations, were demonstrated in
      mice bearing transgenes containing promoter elements from the AChR gamma and
      epsilon subunit genes, each coupled to a nuclear-localized beta-galactosidase
      (nlacZ) reporter. We show that transgene expression is stimulated by the nerve
      derived inducer of AChR expression, ARIA, in myotubes cultured from gamma-nlacZ
      as well as epsilon-nlacZ mice. However, the expression of gamma-nlacZ, but not
      epsilon-nlacZ, is increased by treatment of myotubes with TTX, and the ARIA
      sensitivity of gamma-nlacZ is dependent on the electrical state of the myotube.
      Thus, the promoters of the gamma and epsilon subunit genes may integrate ARIA-
      and activity-dependent signals in different ways to generate their complementary
      patterns of expression.

PMID- 8873767
TI  - Cytoplasmic polyadenylation of activin receptor mRNA and the control of pattern
      formation in Xenopus development.
AB  - The activin receptor, a transmembrane serine-threonine kinase, is a key component
      necessary for pattern formation in early Xenopus development. This protein
      interacts with members of the transforming growth factor beta family and
      stimulates cells of the marginal zone to differentiate along the mesodermal
      pathway. In large part, this function of the activin receptor has been inferred
      from observations of phenotypes induced by injected mRNA encoding wild-type or
      mutant forms of the protein. Naturally occurring activin receptor mRNA is
      maternally inherited and contains within its 3' untranslated region an embryonic
      type cytoplasmic polyadenylation element (CPE), an oligouridylic acid sequence
      that promotes cytoplasmic polyadenylation and resultant translational activation.
      Based on the presence of this element, we predicted in a previous report that
      activin receptor mRNA expression in embryos might be regulated by cytoplasmic
      polyadenylation (Simon and Richter, Mol. Cell. Biol. 14, 7867-7875, 1994). In
      this study, we have tested this hypothesis and show that not only do endogenous
      and injected activin receptor mRNAs undergo cytoplasmic polyadenylation during
      embryogenesis, but also that this process is necessary for stimulating
      translation and inducing the morphological defects observed by mRNA
      overexpression. The activin receptor CPE is bound by a Mr 36 x 10(3) protein in
      vitro, and competition for this factor between mRNAs in vivo inhibits activin
      receptor mRNA polyadenylation. This competition may be responsible for the lack
      of mesoderm formation observed in such injected embryos. These data suggest that
      cytoplasmic polyadenylation controls differentiation and pattern formation in
      early Xenopus development.

PMID- 8873769
TI  - Laminin and heparan sulfate proteoglycan mediate epithelial cell polarization in
      organotypic cultures of embryonic lung cells: evidence implicating involvement of
      the inner globular region of laminin beta 1 chain and the heparan sulfate groups
      of heparan sulfate proteoglycan.
AB  - The extracellular matrix and in particular the basement membrane (BM) play an
      important role in the induction of organotypic rearrangement of cells in culture.
      This process involves cell aggregation, sorting into epithelial and mesenchymal
      components, epithelial cell polarization, and lumen formation. In this study, a
      combination of laminin (LM) and heparan sulfate proteoglycan (HSPG), two major BM
      constituents, induced organotypic rearrangement of embryonic mouse lung cells. In
      the absence of LM/HSPG supplementation, the cells sorted into epithelial and
      mesenchymal compartments but epithelial cell polarization and lumen formation did
      not occur. Neither LM nor HSPG alone could trigger this process. Synthetic
      peptide F-9, representing an amino acid sequence from the inner globular region
      of the laminin beta1 chain (RYVVLPRPVCFEKGMNYTVR) induced organotypic cell
      rearrangement when substituted for LM. Exogenous LM as well as peptide F-9 were
      localized at the epithelial-mesenchymal interface of organotypic cultures, where
      a BM-like structure is formed de novo. Organotypic cell rearrangement was blocked
      by heparin, heparan sulfate, or antibodies against peptide F-9. Binding assays
      indicated that peptide F-9 interacts with HSPG but not with LM or type IV
      collagen. Preincubation of embryonic lung cells with peptide F-9 resulted in a
      significant increase in cell attachment to HSPG but not to other major BM
      constituents. These findings suggest that the interaction between LM and BM HSPG
      is critical for the development of epithelial cell polarization and lumen
      formation. This interaction occurs at the epithelial-mesenchymal interface and is
      mediated by a site in the LM molecule represented by peptide F-9 and the heparan
      sulfate groups of HSPG.

PMID- 8873768
TI  - Interleukin-7 is trophic for embryonic neurons and is expressed in developing
      brain.
AB  - Interleukin-7 (IL7) is a hematopoietic cytokine with critical functions in both B
      and T-lymphocyte development. In this study, we find that IL7 exhibits trophic
      properties in the developing brain as well. Treatment of cultures of embryonic
      brain with exogenous IL7 increases neuronal survival and results in greater
      numbers of cells manifesting neurite outgrowth. As demonstrated with single-cell
      cultures, IL7 acts directly to promote neuronal survival. Expression of the mRNA
      encoding the high-affinity IL7 receptor (IL7R) is observed in vitro in neurons as
      well as in subventricular zone progenitor cells. Phosphorylation of p59fyn, which
      is activated by IL7 in pre-B cells and is thought to be important in neural
      development, occurs rapidly following IL7 treatment of cultured embryonic
      neurons. Additionally, the expression of c-myc mRNA, which is modulated by IL7 in
      lymphoid cells, is upregulated by IL7 in the same CNS cultures. Finally, the
      messenger RNAs encoding IL7 and IL7R are expressed in vivo in developing brain.
      The direct neurotrophic properties of IL7 combined with the expression of ligand
      and receptor in developing brain suggest that IL7 may be a neuronal growth factor
      of physiological significance during central nervous system (CNS) ontogeny.

PMID- 8873770
TI  - Role of galectin-1 in the developing mouse olfactory system.
AB  - Primary sensory olfactory neurons reside in a neuroepithelium lining the nasal
      cavity and project topographically onto the surface of the olfactory bulb, a
      rostral extension of the telencephalon. Galectin-1, a bivalent galactose-binding
      vertebrate lectin, is expressed in the developing rodent olfactory system. In the
      present study, the mouse olfactory neuron cell line 4.4.2 was used to examine the
      role of galectin-l in neurite outgrowth in vitro. Recombinant galectin-l has
      neurite outgrowth-promoting activity when used as a substrate for 4.4.2 cells.
      When either galectin-1 or lactose was added to the culture media, the neurite
      outgrowth-promoting activity was abolished. These results demonstrate that
      galectin-1 can modulate neurite growth in vitro. The in vivo role of galectin-1
      was investigated by examining the topographical organization of the olfactory
      pathway in mice carrying a null mutation for galectin-1. Using Dolichos biflorus
      agglutinin as a convenient histochemical marker of a subpopulation of primary
      sensory olfactory neurons which project topographically to the dorsomedial
      olfactory bulb, we show an aberrant topography of olfactory axons in the null
      mutants. A subset of primary sensory olfactory axons failed to project to their
      correct target sites in the caudal olfactory bulb. These data indicate that
      galectin-1 is involved in the growth and/or guidance of primary sensory olfactory
      axons between the nasal cavity and the olfactory bulb. This is the first
      demonstration that a lectin has neurite outgrowth-promoting activity and plays a
      role in neuronal pathfinding in the mammalian nervous system.

PMID- 8873771
TI  - Expression of CCAAT enhancer binding protein-alpha (C/EBP alpha) in the rat
      ovary: implications for follicular development and ovulation.
AB  - The development of follicles from the antral to the preovulatory stage in the
      mammalian ovary involves both proliferation and differentiation of cells. These
      processes are coordinated by endocrine, paracrine, and autocrine factors in a
      time- and cell-specific pattern. Each stage of development is characterized by
      expression of specific genes the products of which are involved in different
      cellular processes, e.g., signal transduction (cAMP-dependent protein kinases),
      steroidogenesis (cytochrome P450 enzymes). At the nuclear level, the signaling
      pathway from external stimuli converges to modify the mechanisms of transcription
      factors. One such factor, CCAAT enhancer binding protein-alpha (C/EBPalpha),
      participates in differentiation processes of several organs, e.g., liver, adipose
      tissue, and gut. We have previously demonstrated that C/EBPalpha is expressed in
      rat ovarian follicles in a cell-, time-, and hormone-specific manner. This
      increase in granulosa cells was concomitant with the more differentiated
      phenotype. The aim of the present study was to explore the function of C/EBPalpha
      in the rat ovary. To achieve this, the expression of C/EBPalpha in follicular
      cells was attenuated in vivo by the local administration of antisense
      oligonucleotides (AS) into the ovarian bursa, i.e., the sac-like structure
      surrounding the ovary of immature rats. This administration resulted in an
      impaired response to subsequent injections of exogenous gonadotropins (PMSG, hCG)
      with an attenuated expression of C/EBPalpha protein and finally a decreased
      ovulation rate. Furthermore, the morphology of the AS-treated ovary was altered
      with large, oocyte-containing follicles at a time when ovaries exposed to sense
      (S) oligonucleotides demonstrated newly formed corpora lutea. AS also affected
      the expression of the proto-oncogene c-myc, which was elevated by this treatment.
      The administration of S was without effects. Thus, C/EBPalpha seems to be a
      necessary factor for follicular development in the rat ovary.

PMID- 8873772
TI  - TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis
      and vasculogenesis.
AB  - TGF-beta signaling is mediated through two types of serine/threonin kinase
      containing receptors, type I (TGF-betaRI) and type II (TGF-betaRII), which form a
      heteromeric complex. In this signaling complex, ligand binding TGF-betaRII
      phosphorylates and thereby activates the TGF-betaRI to signal downstream
      pathways. To determine the role of TGF-betaRII in embryogenesis, we have
      generated a TGF-betaRII gene (Tgfbr2) knockout mouse line. The heterozygous
      Tgfbr2 knockout mice are developmentally normal. The homozygous Tgfbr2 mutation
      causes defects in the yolk sac hematopoiesis and vasculogenesis, resulting in an
      embryonic lethality around 10.5 days of gestation. This phenotype is
      indistinguishable from the previously reported embryonic lethality by the
      homozygous TGF-beta1 gene (Tgfb1) null mutation. In addition, we have generated
      chimeric mice using a Tgfbr2 (-/-) embryonic stem cell line. Some chimeric mice
      showed several types of congenital anomalies, suggesting that TGF-beta II is
      important for normal development in a variety of organs.

PMID- 8873773
TI  - Scatter factor/hepatocyte growth factor (SF/HGF) induces emigration of myogenic
      cells at interlimb level in vivo.
AB  - The initiating event in the migration of myogenic cells to the limb buds is an
      epitheliomesenchymal transformation of cells located at the lateral edge of the
      dermomyotome. Recently, a targeted mutation of c-met in mice demonstrated an
      essential role of this tyrosine kinase receptor and its ligand, scatter
      factor/hepatocyte growth factor (SF/HGF), in the migration of myogenic cells to
      the limb buds. Here, we show that ectopic application of exogenous SF/HGF induces
      emigration of Pax-3-positive myogenic cells into the lateral plate mesoderm.
      During this process, the lateral portions of the dermomyotomes deepithelialize
      and the basement membrane disintegrates. Detaching myogenic cells do not lose N
      cadherin from their surfaces. We conclude that an HGF/SF- and c-met-mediated
      signal detaches myogenic precursor cells from the somites and thus plays a
      necessary role in the initiation of myoblast migration.

PMID- 8873774
TI  - Biological predictors of 1-year outcome in schizophrenia in males and females.
AB  - This paper describes a prospective study designed to ascertain the predictive
      value of biological factors associated with schizophrenia in males and females.
      In a sample of 59 medication-free schizophrenic inpatients (41 males; 18
      females), we assessed the correlation of four factors--rapid eye movement (REM)
      sleep latency, delta (slow-wave) sleep, dexamethasone suppression test (DST)
      cortisol levels, and ventricle-brain ratio (VBR)--with several dimensions of
      outcome at 1-year post-discharge. In the total sample, shorter REM latency was
      associated with poor outcome on all dimensions measured: rehospitalization,
      employment, social activity, symptomatology, and global functioning. However,
      none of the other biological factors were associated with any measure of outcome.
      The predictive value of REM latency appeared to be gender-specific; in general,
      the relationships between reduced REM latency and poor outcome were consistently
      noted in females, but were not significant in males. These results suggest that a
      common, possibly gender-related, pathophysiological mechanism might underlie both
      abnormal REM latency and poor outcome. The findings underscore the importance of
      considering gender differences in studies of schizophrenia.

PMID- 8873775
TI  - Neurocognitive deficits and social functioning in outpatients with schizophrenia.
AB  - Previous studies suggest that neurocognitive factors may contribute to the
      reduced social functioning of patients with schizophrenia. To assess this
      relationship, we administered a battery of neurocognitive tests and independently
      assessed symptoms (PANSS) and social functioning (SFS) in 88 stable outpatients
      with schizophrenia. We found a significant correlation between neurocognitive and
      social functioning variables. Patients' performance on aphasia, spatial
      organization and visual spatial tasks was correlated with their competence at
      activities of daily living, frequency of social activities and total social
      functioning. Regression analyses of each social functioning scale revealed
      different symptom and neurocognitive predictors. Patients' overall social
      functioning was best predicted by a combination of negative symptoms and aphasia.
      The results support the potential use of interventions to reduce patients'
      cognitive deficits as a means to improve their social outcomes.

PMID- 8873776
TI  - Memory impairment in schizophrenia: its' relationship to executive function.
AB  - The presence of memory impairment in schizophrenia has frequently been documented
      but much less attention has been given to the qualitative aspects of this
      impairment and its association to executive function. Using a cognitive-process
      approach, we examined memory and executive function in 25 patients who met DSM
      III-R criteria for schizophrenia. Patients were matched with 25 healthy
      volunteers. The schizophrenic group was found to have a significant impairment in
      immediate memory, with relatively spared long-delay memory. Performance on verbal
      learning and recognition memory was similar to that of controls. Memory deficits
      were present irrespective of the encoding strategies used and were unrelated to
      chronicity. In addition, the schizophrenics performed worse than controls on
      tests of executive function, but the degree of impairment was greater on tests of
      response initiation and suppression. This pattern of performance resembled that
      found in patients with subcortical or frontal lesions which was supported by some
      significant correlations between aspects of memory and executive function. Our
      results suggest that in schizophrenia, specific executive functions may make a
      selective contribution to the pattern of memory performance in schizophrenia
      which is subserved by frontal and to a lesser extent hippocampal/diencephalic
      systems.

PMID- 8873777
TI  - Contingent negative variation (CNV) and determinants of the post-imperative
      negative variation (PINV) in schizophrenic patients and healthy controls.
AB  - A slowly rising cortical potential shift with negative polarity following the
      imperative stimulus of a forewarned reaction time task, the 'post-imperative
      negative variation' (PINV), is regularly observed in schizophrenic patients but
      not in controls. The topography of the PINV suggests that it may originate in
      frontal cortical regions. We used a task designed to test two putative prefrontal
      cortical functions: working memory and processing of ambiguity. Nineteen patients
      with a chronic schizophrenic disorder and 19 control subjects matched for age,
      sex, and education participated in two experimental sessions. The EEG was
      recorded from frontal, central, temporal, and parietal leads over both
      hemispheres using a DC amplifier. PINV amplitudes were generally larger in
      patients than in controls. If the result of comparing physical features of the
      two successively presented stimuli (warning and imperative stimulus) was
      ambiguous rather than clear, an augmentation of the PINV amplitudes was seen in
      both groups. If this comparison required high rather than low involvement of
      working memory functions, PINV amplitudes were augmented in schizophrenic
      patients only. Scalp distribution of the PINV indicated a left-hemisphere fronto
      central PINV maximum in patients, and a right-hemisphere predominance in
      controls, which was larger following ambiguous stimulus comparisons. These
      results suggest that ambiguity during the comparison of physical features of
      successively presented stimuli may be a general factor of the PINV in
      schizophrenic patients and healthy controls. Augmented involvement of working
      memory functions, presumably subserved by the prefrontal cortex, specifically
      affected the fronto-centrally predominant PINV in schizophrenic patients. This
      result is compatible with the hypothesis of prefrontal cortical dysfunctions in
      schizophrenia.

PMID- 8873778
TI  - Genetic variant near cytosolic phospholipase A2 associated with schizophrenia.
AB  - Two studies were undertaken to determine a possible genetic basis for alterations
      in phospholipid metabolism in schizophrenia. Initial results demonstrated an
      association in 65 schizophrenics compared with a matched normal control
      population. A follow-up haplotype relative risk study of 44 triads (mother,
      father, affected offspring), confirmed the results seen in the association study.
      Results suggest that a genetic variant near the promotor region of the gene for
      cytosolic phospholipase A2, the rate-limiting enzyme in the synthesis of
      prostaglandins from arachindonic acid, is associated with schizophrenia.

PMID- 8873779
TI  - Racial differences in the diagnosis of psychosis.
AB  - In clinical populations, it has been reported that African-American patients are
      more likely to receive a diagnosis of schizophrenia than similar Caucasian
      patients. Factors contributing to this racial discrepancy are poorly defined. The
      authors examined the hypothesis that racial differences in severity of first-rank
      symptoms of schizophrenia contribute to this diagnostic difference. Patients were
      recruited as part of the DSM-IV Field Trial for Schizophrenia and Other Psychotic
      Disorders, and evaluated using a structured rating instrument. Symptom and
      diagnostic comparisons were performed between black and white patients. Black
      patients were significantly more likely than white patients to be diagnosed with
      schizophrenia and less likely with psychotic depression. Racial differences in
      symptom profiles were observed with black patients demonstrating more severe
      psychotic symptoms, in general, and first-rank symptoms, specifically. There were
      no racial differences in rates of affective syndromes or severity of affective
      symptoms. Racial disparity in diagnosis of psychotic patients may be in part
      secondary to more severe first-rank symptoms in black patients, causing
      clinicians to stray from DSM-III-R criteria.

PMID- 8873780
TI  - Presence of dermatoglyphic ridge dissociation in a schizotypy-affected subject in
      a pair of discordant MZ twins.

PMID- 8873781
TI  - Maternal child-rearing attitudes, IQ, and socioeconomic status as related to
      cognitive abilities of five-year-old children.
AB  - The effects of maternal child-rearing attitudes, as measured by the Child Rearing
      Practices Report, on 5-yr.-old children's Verbal IQ and Performance IQ were
      investigated in a Scandinavian sample of 108 boys and 126 girls. The maternal
      child-rearing attitude of Restrictiveness, as defined by scores on the Report,
      showed negative relations to the cognitive measures. However, the significant
      negative relation between Restrictiveness and Verbal IQ, obtained for both sexes,
      disappeared when the effects of maternal IQ and socioeconomic status were
      controlled. The maternal child-rearing attitude of Nurturance, as defined by
      scores on the Report, was significantly related to Verbal IQ and Performance IQ
      for boys only. Significant relationships between scores on Nurturance and
      cognitive abilities of boys remained when the effects of maternal IQ and
      socioeconomic status were controlled.

PMID- 8873782
TI  - Acceptance of rape myths among prosecuting attorneys.
AB  - Surveys containing a measurement of acceptance of rape myths were mailed to 310
      prosecuting attorneys from 87 counties in Ohio. Among the 182 (58.7%)
      participants who responded, self-reported acceptance of rape myths was low. Males
      endorsed rape myths more strongly than females, but the sex differences were
      small in magnitude. No demographic variables were significant in predicting the
      acceptance of rape myths in a regression analysis. The current findings are
      informative because they provide the only direct measure of prosecutors'
      attitudes towards rape victims that have been reported in the past 15 years.

PMID- 8873783
TI  - Dimensionality of a scale of adjustment to unemployment.
AB  - Many of today's unemployed are middle managers or midcareer professionals who
      lost their jobs through no fault of their own. This study examined psychological
      effects of unemployment on 178 professionals using an adaptation of Kaufman's
      adjustment to unemployment scale. Analysis indicated two factors, negative affect
      (which includes anxiety, burden, irritation, resentment, and anomie; alpha = .69)
      and general affect (self-esteem, depression, and life satisfaction; alpha = .73).
      Implications for the study of unemployed professionals are discussed.

PMID- 8873784
TI  - Elements of behavioral health intervention in geriatric long-term care settings.
AB  - The somewhat alarming incidence of mental disorders among institutionalized
      elderly persons has necessitated improved ways of dealing with their behavioral
      health needs. Because conventional psychotherapy has not been feasible with this
      population, alternative types of behavioral health interventions have been
      suggested. The present paper lists a number of elements which may be helpful in
      delivering focused behavioral health services to residents in long-term care
      facilities.

PMID- 8873785
TI  - Health care trends and holding the line on costs.
AB  - The increasing reliance on third party payment of health care costs has resulted
      in people assuming less personal financial responsibility for their own health
      care. Lessened personal financial responsibility has resulted in greater use of
      the Health Care System and so has led to greater costs for health care. This
      increased cost has focused attention on cost control and implementation of
      measures designed to control costs. The cost control measures, however, are
      flawed. Were the purchase of health care once again to become subject to
      consumers' buying decisions, health care costs would be brought under control.

PMID- 8873786
TI  - The role of emotional and socio-cognitive patterns in obesity: eating attitudes
      in obese adolescents before and after a dietary-behavioural therapy.
AB  - The aim was to examine attitudes towards eating in a group of obese and nonobese
      female adolescents (N = 200), in particular whether obese subjects have
      characteristic attitudinal patterns associated with obesity. Analysis concluded
      that our sample, both overweight and normal subjects, share the negative
      stereotypic attitudes towards obese persons. However, there was a considerable
      difference in emotional evaluation of eating behaviour. If normal subjects
      attribute a strong negative emotional connotation, obese subjects not only did
      not recognise the "abnormality" of overeating, but preferred it. This can be
      explained by the presence of an association of strength and power with
      overeating: at the moment of eating, obese subjects feel themselves "strong" and
      even "superior," thereby compensating for their rather weak and fragile
      personalities. The emotional evaluation of eating behavior did not change after a
      10-week dietary/behavioural treatment.

PMID- 8873787
TI  - Stanford-Binet: Fourth Edition short forms with underachieving and learning
      disabled students.
AB  - 55 students referred to a Child Development Center for academic underachievement
      and suspected learning disabilities were administered the Stanford-Binet
      Intelligence Scale: Fourth Edition, Pearson product-moment correlation
      coefficients of .98, .95, and .90 were obtained for the Test Composite with those
      for 6-, 4-, and 2-test Partial Composites derived from this administration,
      respectively. These values are compared with coefficients reported for other
      populations, and the suitability of the Stanford-Binet Partial Composites for
      screening underachievement and learning disabilities is discussed.

PMID- 8873788
TI  - Loneliness and creativity in adolescents.
AB  - Samples of 107 early, 81 middle, and 112 late adolescents responded to the UCLA
      Loneliness Scale and The Creativity Scale of the Adjective Check List. Contrary
      to the hypothesized direction, statistically significant inverse correlations (
      .19 to -.33) were found between scores on measures of loneliness and creativity
      in all three adolescent samples. Findings are interpreted within the
      conceptualizations in which the relationship between loneliness and creativity
      were proposed.

PMID- 8873789
TI  - Scores on self-actualization for gifted junior high school students.
AB  - Self-actualization scores of 47 gifted students in Grades 7 and 8 were assessed
      using the Reflections of Self by Youth (ROSY), the Maslowian Scale, and the
      Personal Orientation Inventory. No gender differences were observed. Students in
      Grade 7 scored significantly higher on the ROSY; students in Grade 8 scored
      significantly higher on the Maslowian Scale Psychological subscale and Total
      score. Scores on the Maslowian Scale Fundamentals and Self-actualization
      subscales and Personal Orientation Inventory were not different for any group.
      Correlations among the three measures of self-actualization are presented.

PMID- 8873790
TI  - Prediction of cervical cancer screening using the theory of reasoned action.
AB  - Rates of Pap smears among 72 adult women were shown to be suboptimal and
      predicted indirectly by attitudes and subjective norms. Women perceived these
      examinations to be unpleasant and embarrassing.

PMID- 8873791
TI  - Rehearsal of positive self-statements and restructured negative self-statements
      to increase self-esteem and decrease depression.
AB  - Rehearsal of self-statements was used to modify scores on self-esteem and
      depression of 60 undergraduates low in self-esteem. Subjects in the rehearsal
      group were instructed to read 15 self-statements to themselves three times a day
      for two weeks. These self-statements were derived from a combination of the most
      frequently occurring negative thoughts and least frequently occurring positive
      thoughts given by the subject on the Automatic Thought Questionnaire-Revised.
      Negative thoughts endorsed by subjects on the questionnaire were restructured
      into more adaptive self-statements, and endorsed positive thoughts were modified
      into self-statements which accentuated the positive aspect of the thought. This
      procedure significantly increased scores on self-esteem and decreased depression
      scores. The questionnaire was effective in identifying positive and negative self
      statements which were significantly related to scores on self-esteem and
      depression after 2 weeks.

PMID- 8873792
TI  - Sex-role orientation among incarcerated women.
AB  - This study of 120 women inmates of a state prison showed that sex-role
      orientation was related to the type of offence committed by women but, contrary
      to the hypothesis about the "new" female offender, violent offenders were more
      traditionally feminine than financial and drug-related offenders. Drug offenders
      had high rates of undifferentiated ratings. Women became more traditionally
      masculine or feminine with length of incarceration. Women who had children were
      more likely to score as traditionally feminine.

PMID- 8873793
TI  - Asian-American men's acculturation and gender-role conflict.
AB  - There is limited research on Asian-Americans' acculturation and conflicts with
      contemporary gender roles. This research assessed three samples of Asian-American
      men's acculturation and gender-role conflict. Differences between Chinese
      American, Japanese-American, and Korean-American men's acculturation and the four
      patterns of gender-role conflict were analyzed. The relationship of demographic
      and acculturation variables to gender-role conflict was also calculated. Subjects
      (N = 125) were administered a demographic questionnaire, the Suinn-Lew Asian Self
      identity Acculturation Scale, and the Gender-role Conflict Scale. Multivariate
      analysis of variance showed no differences between the Asian-American groups on
      acculturation and the four patterns of gender-role conflict. A canonical
      correlation analysis indicated one significant variate connecting acculturation
      with two patterns of issues of gender-role conflict: success, power, and
      competition and restrictive emotionality. Methodological limitations and research
      are mentioned.

PMID- 8873794
TI  - The compensatory model in weight control: relapse prevention revisited.

PMID- 8873795
TI  - Comparison of differences in the association of social support and adjustment
      between Chinese and Japanese students in Japan: a research note.
AB  - This study examined the associations of Japanese students' social support, and
      their adjustment in comparison with those of Chinese students. Needed and actual
      support and the discrepancy between the two were examined, and Japanese
      professors and other Japanese students were employed as major sources of support.
      Respondents were 68 Japanese and 64 Chinese students in Japan. Analyses indicated
      that, although there was no significant difference between Japanese and Chinese
      students' adjustment, the associations of social support and adjustment were
      different between the two groups. This study also documented that Japanese
      professors were important as a source of support for Chinese students more than
      they were for Japanese students and that the support needed from other Japanese
      students correlated negatively with the adjustment of Chinese students.

PMID- 8873796
TI  - Association of depressive symptoms and school adolescents' smoking: a cross
      lagged analysis.
AB  - This study examined the association of depressive symptoms of adolescents and
      their smoking behavior. A national cohort sample of school adolescents (N =
      5,855) who participated in the 1989 and 1993 Teenage Attitudes and Practices
      Survey was obtained. The information from this survey included measures of
      smoking behavior and a series of factors related to depressive symptoms during a
      3-yr. span. A cross-lagged analysis with Kendall tau b correlations was used.
      Judging from the magnitude of the cross-lagged correlations, the direction of
      causation cannot be ascertained. Rather, a reciprocal relationship between
      depression and smoking may be suggested.

PMID- 8873797
TI  - An animal rights attitude survey of undergraduate psychology students.
AB  - An animal rights attitude survey of 46 statements on various issues related to
      animal rights was given to 112 freshmen who were near the end of their first
      college course in introductory psychology and to 63 junior and senior psychology
      majors. A factor analysis yielded a multidimensional structure with attitudes
      toward animal research, nonresearch, environment, and evolution as factors.
      Beginning psychology students had a more negative attitude toward animal research
      than did psychology majors; however, psychology majors displayed a more positive
      attitude toward the environment and toward animal rights issues not involving
      animal research.

PMID- 8873798
TI  - Preliminary study of effect of the Iraqi invasion on addictive behaviour in
      Kuwait.
AB  - During the Iraqi invasion, Kuwait was flooded with alcoholic substances and drugs
      which, if used, could induce harmful radical changes in the personality and
      behaviour of Kuwait citizens (not Islam prohibits alcohol). After liberation
      aggressive behaviour prevailed among some Kuwait citizen groups, including
      addicts, as the government of Kuwait had not yet reestablished discipline and
      control over the citizens. Forensic cases of addicts referred to Kuwait
      Psychiatric Hospital before and after the invasion were examined. Marked
      differences were observed concerning age, education, occupation, marital status,
      addictive behaviour, crime committed, and place of referral and discharge.

PMID- 8873799
TI  - Unemployment and alcohol consumption.

PMID- 8873800
TI  - Narcissism and hostility.
AB  - Small to moderate correlations were observed for scores of 32 males and 66 female
      undergraduates on the Narcissistic Personality Inventory and the Buss-Durkee
      Hostility Inventory. Developmental questions are raised.

PMID- 8873802
TI  - Friendships, femininity, and reaction to affective arousal.
AB  - This study examined relations between college women's scores on femininity and
      their same-sex friendships and how these women's perceptions were influenced by
      induction of success or failure. 200 undergraduate women described themselves and
      their best friends on the dominance and submissiveness scales of the
      Interpersonal Adjective Scales and also completed the Behavioral Self-report of
      Femininity and a biographical information sheet. Mean ratings of dominance were
      above average both for self and best-friend ratings, but these two dominance
      ratings were not significantly correlated. However, women viewed themselves as
      similar to their best friends on submissiveness characteristics. Highly feminine
      women described themselves as more dominant than less feminine women. Highly
      feminine women also experienced less anxiety and fatigue as measured by the
      Profile of Mood States in response to failure induction than less feminine women.
      Both sets of results are contrary to expectations, but the behavioral definition
      of femininity was different from that used earlier.

PMID- 8873801
TI  - Longitudinal survey of mental retardation during adolescence among Italian
      pupils.
AB  - In this paper are analysed the increases in mental age during a 3- to 31/2-yr.
      interval of 54 adolescents classified as mildly or moderately mentally retarded
      who had participated in rehabilitation therapy (therapy) or had no therapy
      (control). Analysis showed that the rehabilitation therapy significantly
      increased mental age only for subjects with mild retardation but not those with
      moderate mental retardation.

PMID- 8873804
TI  - Membership in associations and suicide rates.

PMID- 8873803
TI  - Reliability and validity of AIDS victim blaming scales.
AB  - Scales were developed to measure the tendencies to blame AIDS victims or the
      society in which victims live. Data from a sample of 874 students were used to
      examine the construct validity and reliability of the scales. The list-wise
      deletion reduced the sample size to the usable sample size of 824. The data
      showed satisfactory validity and reliability of the scales so they may be used to
      study attitudes toward those who are suffering from AIDS and related problems.

PMID- 8873805
TI  - Evaluation of toy variation on engagement in a leisure activity of two children
      with profound multiple handicaps.
AB  - We conducted two studies to examine whether satiation occurs during leisure
      activities for children with profound multiple handicaps and whether it can be
      prevented by the alternate use of a sufficient number of different toys. The two
      studies were done in a training program in which the use of a switch connected to
      battery-operated toys was taught to two children with profound multiple
      handicaps. In Study I (Child 1), two experimental conditions were compared:
      variation (use of 5 toys in the same learning session) and identity (use of only
      one of these toys throughout the session). The variation condition produced
      higher and more stable performance than the identity condition, which yielded a
      progressive decrease in the appearance of the target behavior. In Study 2 (Child
      2), satiation appeared from one session to another and the rate of responding
      increased when a new toy was presented. Some practical and theoretical
      implications are discussed.

PMID- 8873806
TI  - Does the MMPI PTSD-PK scale measure robustness?
AB  - Research evaluating the diagnostic value of the MMPI PK scale for determining
      Posttraumatic Stress Disorder has been consistently positive. Various cut-off
      points have been suggested, depending on the population studied. The current
      study, involving a select group of police candidates from middle-sized midwestern
      towns, suggests that low PK scores may represent robustness. These subjects as a
      group made low use of health and mental health services and obtained very low PK
      scores (T = 41), although they made average scores on the clinical scales.

PMID- 8873807
TI  - Accurate knowledge about suicide and personality.

PMID- 8873808
TI  - Intrapatient agreement on phenomenology of panic attacks.
AB  - Panic disorder is common in primary care settings and such a physician is often a
      patient's initial contact with the health care system. Previous work concerning
      the homogeneity of panic phenomenology across patients is contradictory. The
      purpose of this pilot study was to assess the intrapatient homogeneity of panic
      attacks and to examine associations between measures of homogeneity and
      physicians' confidence in the diagnosis. Ten patients meeting DSM-III-R criteria
      for panic disorder completed a diary documenting the symptomatic phenomenology of
      five consecutive panic attacks. In addition, the physician rated his diagnostic
      confidence for each patient. Patterns of symptoms and their sequences during
      panic showed good agreement within patients as did patterns of abatement and of
      presence of a precipitating event. The physician's diagnostic confidence was
      inversely related to agreement on symptom severity and variance of duration of an
      attack. This study suggests intrapatient homogeneity on most measures.

PMID- 8873809
TI  - Relationship between exhaustion and postnatal depression.
AB  - The period after the birth of a child may be characterized by occasions of
      physical exhaustion. Mothers who self-reported having experienced postnatal
      depression in the past year and physical exhaustion were examined.

PMID- 8873810
TI  - Characteristics and motives of volunteers in wildlife rehabilitation.
AB  - Although wildlife rehabilitation relies heavily on volunteers, the
      characteristics and motivations of such volunteer workers have not been studied.
      80 volunteers from three San Francisco Bay Area Rehabilitation Centers, were
      interviewed about their preferences in working with animals and people, their
      methods of dealing with grief and failure over animals' deaths, and the onset of
      their interest in and motives for working in a difficult field. A significant
      number had owned pets in childhood as well as currently. 40% preferred working
      only with animals to working with both animals and people. 34% stayed in
      rehabilitation because they loved and wanted to help animals; 23% enjoyed hands
      on nurturing; and the remainder primarily felt they were giving back to Nature a
      part of what people have taken from it.

PMID- 8873811
TI  - Assessing three adolescent groups in New Mexico using the Problem-oriented
      Screening Instrument.
AB  - Analysis of responses of 289 rural white, Hispanic, and Navajo adolescents to 10
      items of the Problem-oriented Screening Instrument showed the 40 Navajo girls
      scored highest in over-all pathology followed by 40 Navajo, 55 white, and 51
      Hispanic boys. Both the Hispanic and white girls (ns = 49 and 54, respectively)
      scored below the minimum mean score of 38 for pathology.

PMID- 8873812
TI  - Robustness of taxometric analysis with skewed indicators: I. A Monte Carlo study
      of the MAMBAC procedure.
AB  - A small Monte Carlo study was conducted to determine whether Meehl and Yonce's
      (1994) MAMBAC procedure--a taxometric method for testing between discrete and
      continuous models of latent variables--is robust when the latent variable and its
      manifest indicators are skewed. Analysis of constructed data sets containing
      three levels of skew indicated that the MAMBAC procedure is highly unlikely to
      yield spurious findings of discreteness ("taxonicity") even when skewness is
      considerable. MAMBAC appears to be a robust and promising addition to the family
      of taxometric procedures.

PMID- 8873813
TI  - On-line sexual addiction: a contemporary enigma.
AB  - On-line computer bulletin boards, although screened for offensive content, have
      become a breeding ground for sexually related material and erotic-chat networks.
      Participants can interact individually or in groups (chat rooms) on a host of
      sexually perverse subjects. Persons afflicted with various erotic predilections
      via 'cybersex' have recently gained the attention of mental health professionals.
      The authors report on a 'cybersex' group in treatment for sexual addiction.

PMID- 8873814
TI  - Responses to Bortner's scale and the eight basic emotions by patients with acute
      coronary heart disease at hospital admission and discharge.
AB  - We examined the prevalence of Type A behavior indicated on Bortner's scale and
      the Emotion Profiles of Plutchik in 190 patients, 134 men and 56 women (M age =
      50 yr., SD = 9) with acute coronary heart disease at hospital admission and
      discharge. Type A classification was significantly more common for patients with
      acute coronary heart disease (75.5% versus 65%) than for the control group.
      Patients with acute coronary heart disease scored lower on Distrust and
      Dyscontrolled than the control group. Patients with unstable angina had
      significantly higher mean scores on Bortner's scale than patients with acute
      myocardial infarction and recurrent myocardial infarction at hospital discharge.
      Patients with recurrent myocardial infarction scored lower on Distrust and higher
      on Timid than patients with unstable angina at hospital admission and discharge.
      This research suggests that Type A behavior and some emotions are associated with
      acute coronary heart disease. There was a difference in scores on the Emotions
      Profiles and scores on Type A behavior in relation to type of acute coronary
      heart disease. The addition of counseling for Type A behavior to standard cardiac
      counseling was suggested for reduction in scores on Type A behavior.

PMID- 8873815
TI  - Instructors of psychotherapy in M.A. and Ph.D. clinical programs.
AB  - The present study investigated the characteristics and orientations of the
      instructors of the initial psychotherapy course of the 44 members and affiliates
      of the Council of Applied Master's Programs in Psychology. Also examined were the
      focus of instruction in the course and the teachers' style of instruction.
      Responses for 26 completed surveys (58%) were compared with responses from
      instructors of initial psychotherapy courses in 69 of the 170 APA accredited
      doctoral programs. Five general theoretical orientations were represented by the
      M.A. instructors with 28% self-identifying as humanistic, 24% as dynamic, 20% as
      cognitive behavioral, 16% as interpersonal, and 12% as behavioral. No significant
      differences were found on demographic characteristics, theoretical orientation,
      focus of instruction, or method of instruction between instructors in M.A. and
      those in Ph.D. programs.

PMID- 8873816
TI  - A cross-cultural study of attitudes towards seeking psychological help.
AB  - Among 98 Asians and 78 Caucasian British subjects physicians' ratings of
      somatisising predicted patients with less positive attitudes towards
      psychotherapy. Whether a psychotherapist had been seen previously was also
      significant as was years lived in Great Britain.

PMID- 8873817
TI  - Development and validation of an inventory for measuring job satisfaction among
      family physicians.
AB  - The aim was to develop and validate a measure of job satisfaction among family
      physicians. The construct of job satisfaction was developed theoretically, then
      the semantic network technique was used for the construction of the items. 80
      semantic differential items in a random order were related by nine physicians.
      Four dimensions integrated the construct: "job satisfaction," "health
      institutions where I work," "my patients," and "myself as a doctor." The average
      Cronbach alpha was .81. In the factor analysis, four factors were obtained in
      each dimension except that of "my patients," for which two were obtained. These
      factors accounted for at least 44% of the construct developed. The semantic
      network technique may be useful.

PMID- 8873818
TI  - Eating disorders, depression and suicidal preoccupation in a nonclinical sample.

PMID- 8873819
TI  - Ethnic-racial differences in psychological stress related to gay lifestyle among
      HIV-positive men.
AB  - To examine whether there were any ethnic-racial differences among 144 HIV
      infected gay men (47 Caucasian, 48 African-American, and 49 Puerto Rican) on
      psychological stressors related to the gay lifestyle, responses to the Gay
      Lifestyle Hassles scale were analyzed. The African-American and Puerto Rican men
      reported significantly higher scores on frequency of Gay lifestyle Hassles and
      cumulated severity of Gay Lifestyle Hassles over-all than Caucasian men. The
      results suggest that HIV-infected ethnic-minority gay men were more prone to
      psychological stress related to the gay lifestyle than HIV-infected Caucasian gay
      men, which may have negative consequences for their mental and physical health.

PMID- 8873820
TI  - Altruism toward deviant persons in cities, suburbs, and small towns.
AB  - Of 405 letters "lost" in Florida, 167 were returned in the mail (the altruistic
      response). Addressees' affiliations were significantly associated with return
      rates; fewer highly deviant "Communist" and "FLAB" addressees were returned. The
      associations of urban size and addressees' affiliations with altruistic responses
      in 31 cities and 10 suburbs were substantially greater than in 5 small towns but
      only moderately so if the addressee was highly deviant. Small town residents
      returned only 7 letters to highly deviant addressees compared to 31 for nonrural
      residents.

PMID- 8873821
TI  - On the reliability of the youth self-report.

PMID- 8873822
TI  - Relations of cognitive functions associated with the frontal lobes and learning
      disorders in children.
AB  - Various cognitive processes associated with the frontal lobes and their influence
      upon learning and learning disorders in children were investigated. Subjects were
      29 7- to 12-yr.-old boys and girls. Analysis of variance suggested that, as a
      group, the learning-disabled children scored lower on tasks with a high demand
      for selective attention, ability to inhibit interference, sequential reasoning,
      and integration and organization of new information--cognitive functions commonly
      attributed to the frontal lobes. The relationship of these cognitive functions to
      acquisition of basic academic skills is discussed.

PMID- 8873823
TI  - Cultural evolution, suicide and homicide.

PMID- 8873824
TI  - Loneliness, perceived social support, and anxiety among Israeli adolescents.
AB  - This study was designed to investigate the variables of social support,
      loneliness, and anxiety among two groups, i.e., participants who identified with
      the label "I am a lonely person" (Lonely group; n = 37) and those who did not
      identify with this label (Not lonely group; n = 107). Based on the findings of a
      1994 study of South Pacific participants, hypotheses were formulated and tested
      using the grouping variable. As expected, significant correlations for scores on
      loneliness with social support and with anxiety were noted. Also, as expected,
      there were significant differences between the two groups on social support,
      loneliness, and anxiety. While such results support earlier findings it appears
      the association of loneliness and perceived social support may be more complex
      than proposed earlier. For the lonely group anxiety is significantly correlated
      with a need to seek acceptance.

PMID- 8873825
TI  - Suicide in Indian states and religion.

PMID- 8873826
TI  - Neuroticism and sense of coherence.
AB  - The relationship of scores on sense of coherence with measures of personality
      traits was assessed using the 29-item Orientation to Life Questionnaire and the
      Eysenck Personality Inventory. In one group of 95 mixed-sex students scores on
      Neuroticism bore a highly negative relationship with scores on sense of
      coherence. Findings support the current literature that health questionnaires may
      indirectly measure Neuroticism and that personality variables play an important
      role in general health.

PMID- 8873827
TI  - Comparison of four health-care disciplines on the Facts on Aging and Mental
      Health Quiz.
AB  - Professionals in four health-care disciplines were given the Facts on Aging and
      Mental Health Quiz to assess their knowledge in these areas. All groups scored
      means above 70%, indicating considerable knowledge which would help in their
      provision of services to older adults.

PMID- 8873828
TI  - Multidrug resistance among methicillin-resistant Staphylococcus aureus in Greece.
AB  - A total of 472 strains of Staphylococcus aureus isolated in a university hospital
      in Thessaloniki, Greece during 1993-1994 were studied; 202 (42.8%) of them were
      characterized as methicillin-resistant (MRSA) and were mainly recovered from
      respiratory materials. The minimal inhibitory concentrations (MICs) of
      methicillin-susceptible (MSSA) and methicillin-resistant strains to 10
      alternative antibiotics were also compared. All MRSA isolates were resistant to
      penicillin and most of them, in contrast to MSSA, exhibited resistance to
      gentamicin, tobramycin, tetracycline, erythromycin and ciprofloxacin with
      resistance rates ranging from 89.6% to 59.4%. Also, considerable proportions of
      MRSA were found resistant to co-trimoxazole (47.0%) and rifampicin (27.7%). All
      isolates were sensitive to vancomycin while susceptibility to chloramphenicol was
      of equal incidence among the examined populations. Overall, MRSA vs. MSSA
      exhibited a significantly (chi 2; P < 10-8) higher incidence of resistance to 8
      out of the 10 antibiotics examined.

PMID- 8873829
TI  - Influence of subinhibitory concentrations of ceftazidime, ciprofloxacin and
      azithromycin on the morphology and adherence of P-fimbriated escherichia coli.
AB  - The influence of subinhibitory concentrations (1/2, 1/4, 1/8, 1/16 and 1/32 x
      MIC) of ceftazidime, ciprofloxacin and azithromycin on the morphology and
      adherence of 29 wild-type P-fimbriated strains of Escherichia coli was studied.
      Bacterial adherence to the Buffalo green monkey (BGM) cell line was tested before
      and after treatment with antibiotics and detected by means of an
      immunofluorescence staining. Significant dose dependent reduction of bacterial
      adherence was observed, which correlated with the alterations in bacterial cell
      morphology. After exposure of strains to sub-MICs of antibiotics, normal shapes,
      spherical forms and filaments were noted. The greatest filamentation and the
      greatest loss of adherence ability occurred at 1/2 x MIC of ceftazidime.
      Treatment with sub-MICs of ciprofloxacin resulted in shorter filaments, while
      filamentation did not occur after bacterial exposure to sub-MICs of azithromycin.
      Azithromycin was least damaging to the adherence ability of E. coli and at a
      concentration of 1/2 x MIC caused globoid cell formation.

PMID- 8873830
TI  - Mobilization of antibiotic resistance for transfer in Pseudomonas aeruginosa.
AB  - We describe a phenomenon of mobilization of antibiotic resistance from non
      transferring strains of Pseudomonas aeruginosa by cultivation with strains of
      P.aeruginosa capable of transferring determinants of antibiotic resistance to a
      susceptible recipient strain by triparental cross. In this report we described
      two strains of P.aeruginosa capable to mobilize for transfer the resistance
      determinants in strains of P.aeruginosa with multiply antibiotic resistance which
      were not themselves transferable to Pseudomonas recipient strains. Two strains of
      P.aeruginosa No. 282 and 283 from Bata's Hospital in Zlin, Czech Republic, were
      used as donor strains for experiments in triparental crosses. They were resistant
      to carbenicillin (CAR), kanamycin (KAN), cefalotin-cefazolin (CFR), cefotaxime
      (CTX), ceftazidime (CAZ) and aztreonam (AZA). Both strains transferred CFR
      resistance to Escherichia coli K-12 rif+ recipient, but not to P.aeruginosa PAO
      recipients. In a second system, a strain of P.aeruginosa No. 76 from Frankfurt
      University Clinics was used as a donor strain. It transfers CAR resistance to PAO
      1670 rif+, but not to E. coli K-12 rif+. Two strains of P.aeruginosa from
      Frankfurt University Clinics No. 76 and 229 were used as intermediary recipient
      strains. They were resistant to CAR, KAN, CTX, CAZ, AZA, imipenem (IMP) and
      ofloxacin (OFL). Strain No. 229 did not transfer any antibiotic resistance to any
      of both final recipient strains. Strain No. 76 transfers, as indicated, CAR
      resistance determinant to PAO 1670 rif+ recipient strain. Strains of E. coli K-12
      No. 3110 rif+ and P.aeruginosa PAO 1670 rif+ were used as final recipient
      strains.

PMID- 8873831
TI  - The origin, by mutation, of high level resistance to ceftazidime and cefotaxime
      in a clinical isolate of Enterobacter cloacae.
AB  - Although strains of Enterobacter sp. produce a chromosomal AmpC beta-lactamase,
      they have been, in general, susceptible to cefotaxime or ceftazidime. But now
      resistance to ceftazidime has increased in nosocomial Enterobacter strains,
      reaching the level of 40%. A chromosomal mutation in the amp operon coding the
      production of AmpC type beta-lactamase may cause a change in the conversion of a
      susceptible strain of Enterobacter to a highly resistant mutant. The production
      of AmpC enzyme is inducible and third-generation cephalosporins are weak inducers
      of AmpC production. Spontaneous mutations (or insertions of transposons) in the
      regulatory region of amp operon might create constitutive (derepressed)
      overproducers of large amounts of AmpC molecules. As a consequence, such cells
      acquire a stable resistance to beta-lactam antibiotics including cefotaxime or
      ceftazidime. We describe the origin of mutants of a clinical isolate of
      Enterobacter cloacae that acquired high-level resistance to ceftazidime followed
      by the resistance to cefotaxime and/or aztreonam due to a second mutation.

PMID- 8873832
TI  - Greek physicians' and dentists' compliance with the British society for
      antimicrobial chemotherapy (BSAC) guidelines for preventing bacterial
      endocarditis.
AB  - Two thousand questionnaires inquiring about applied prophylaxis for bacterial
      endocarditis were sent to practicing doctors in Greece. Two hundred and ninety
      nine questionnaires were completed and returned (15% response rate) and were
      subsequently divided into two groups: Group A (163) consisting of responses from
      dentists, chest physicians and ear, nose and throat (ENT) specialists and group B
      (136) including responses from gastroenterologists, gynecologists, urologists and
      radiologists. The percentage of correct answers given in response by clinicians
      in Groups A and B to the main questions and in accordance with the 1992
      guidelines of the British Society for Antimicrobial Chemotherapy (BSAC) were
      respectively: (a) 53% vs 35% asked patients their previous history pertaining to
      valve disease, rheumatic fever or prosthetic valve surgery; (b) 55% vs 33%
      administered prophylaxis to patients with relevant history prior to medical
      procedures; (c) 67% vs 0% of prescribing doctors administered the appropriate
      antibacterials; (d) 33% vs 31% initiated prophylaxis in proper timing prior to
      medical procedure; (e) 14% vs 13% administered antibiotics in correct
      time/route/duration of infusion where applicable, prior to medical procedure; (f)
      7% of group A doctors administering recommended antibiotics, implemented
      prophylaxis with correct time/route/dosage while, although none of group B
      doctors administered recommended antibiotics, 7% implemented prophylaxis with
      correct time/route recommendations; (g) an overall 2% of doctors from both groups
      met the BSAC recommendations. In conclusion, it is imperative that the
      appropriate training of doctors in all subspecialties regarding prophylaxis of
      bacterial endocarditis and according to current recommendations be carried out.

PMID- 8873833
TI  - Aminoglycoside prescription, therapeutic monitoring and nephrotoxicity at a
      university hospital in Saudi Arabia.
AB  - We studied the use of aminoglycosides at King Abdulaziz University Hospital
      (KAUH), Jeddah, Saudi Arabia, including prescriptions, dosage, serum levels,
      toxic factors and treatment outcome. Two hundred and fifty-six patients on
      aminoglycosides were involved in the study period November-December 1994: 24
      (9.4%) patients were on amikacin and 232 (90.6%) patients were on gentamicin. The
      serum concentration was below the therapeutic range in 75% of the patients on
      amikacin and 50% on gentamicin. Serum concentrations within the therapeutic range
      (> 20 micrograms/ml; < 35 micrograms/ml for amikacin, and > 6 micrograms/ml and <
      10 micrograms/ml for gentamicin) were achieved in 4% and 44% of patients
      respectively. The dosage was adjusted during therapy for 57% of the patients
      because of low levels, and for 43% of the patients because of toxic levels. More
      than 30% of the patients had their serum monitored for the first time 3 days
      after starting aminoglycoside therapy. Aminoglycosides were discontinued before
      the end of the course in 157 (62%) patients because 24% of them had developed
      toxic levels and 24% had not responded to the treatment. Successful outcome was
      achieved in 170 (66%) of the patients, however, 50% of them had inappropriate
      serum levels. The risk factors that are significantly associated with
      aminoglycoside nephrotoxicity were duration of therapy (P = 0.008), renal, liver
      diseases and ampicillin given concurrently with the aminoglycosides (P = < 0.05).

PMID- 8873835
TI  - Prophylactic administration of amoxicillin and clavulanic acid in pregnant women
      with premature rupture of the membranes.
AB  - Seventy-five pregnant women (mean gestational age 32.26 weeks, range 20-36 weeks)
      with premature rupture of the membranes (PROM) were admitted in our department
      during 1989 and the first 6 months of 1990. Amoxicillin and clavulanic acid was
      initially administered at a dose of 1.2 g i.v. every 8 hours for 3-4 days and was
      followed by oral administration of 625 mg every 8 hours until labor. Sixty-one
      patients (mean gestational age 32.6 +/- 2.3 weeks, range 26-36 weeks) achieved an
      uncomplicated course of their pregnancies with a mean time of 11.4 +/- 5.7 days
      (range 3-27 days), from rupture to delivery. Fourteen women (mean gestational age
      30.8 +/- 5 weeks, range 20-36 weeks) developed chorioamnionitis 3.5 +/- 0.9 days
      (range 1.4-5.6 days) after the rupture with several degrees of leukocyte
      infiltration of the membranes, placenta and the umbilical cord. Five women (mean
      gestational age 23.8 +/- 2.3 weeks, range 20-26 weeks) had complications
      resulting in fetal/infant death, three of them because of fetal sepsis
      (Escherichia coli, Pseudomonas aeroginosa, Staphylococcus aureus). The newborns
      were followed up 6 months from delivery and had no signs of drug influence. Few
      side effects were observed with the chief complaints involving the
      gastrointestinal tract (4%). No one discontinued the drug. It seems therefore,
      that the prophylactic administration of amoxicillin and cluvalanic acid in women
      with PROM is associated with a significant prolongation of pregnancy and with a
      reduction in the incidence of fetal/maternal infections.

PMID- 8873834
TI  - Efficacy of sulbactam-ampicillin for the treatment of severe diabetic foot
      infections.
AB  - Diabetic foot infections, a frequent and serious cause of morbidity in patients
      with diabetes mellitus, are caused by anaerobic and aerobic bacteria. Given the
      fact that seriously impaired host defense factors are almost always present in
      these patients, bactericidal agents with a broad spectrum of antimicrobial
      activity are required for their treatment. Seventy-four patients with diabetic
      foot infections were treated with parenteral sulbactam-ampicillin (1.5 g,
      q.i.d.). All patients were followed-up prospectively in order to determine the
      efficacy and safety of sulbactam-ampicillin. The mean duration (+/- SD) of
      treatment in patients with osteomyelitis (n = 49) and soft tissue infections (n =
      25) was 41 +/- 5 and 14 +/- 3 days, respectively. Infected limbs were amputated
      at various levels in 14 patients (19%). Clinical cure rates were 86% and 100% in
      patients with osteomyelitis and with soft tissue infection, respectively. The
      most frequent side effect was diarrhea and observed in 10 patients (14%). The
      results of the present study indicate that sulbactam-ampicillin is safe and
      effective in the treatment of diabetic foot infections.

PMID- 8873836
TI  - Does verapamil help overcome multidrug resistance in tumor cell lines and cancer
      patients?
AB  - The aim of these experimental and clinical studies was to determine if verapamil
      helps overcome multidrug resistance in tumor cells and in cancer patients. The
      effect of the calcium channel blocker verapamil on the antiproliferative activity
      of epirubicin (Farmorubicin, Farmitalia) was followed up in in vitro studies on
      two constant human leukemia cell lines: CEM/O (P-gp negative) and CEM/VCR 1000
      with a positive multidrug resistant (MDR) phenotype. The MTT assay was used to
      study the antiproliferative activity. Verapamil in concentrations of 3 and 10
      micrograms/ml enhanced by 10-fold and 19-fold, respectively, the effect of
      epirubicin in CEM/VCR 1000 cells and had no significant effect on epirubicin
      activity in CEM/O. Eleven patients with measurable stage IV breast cancer,
      clinically resistant to anthracycline treatment, received the FEC combination (5
      fluorouracil-epirubicin-cyclophosphamide) twice with verapamil pretreatment, p.o.
      at the doses of 1280-2560 mg. There were two complete remissions (soft tissue
      metastases), four partial remissions (soft tissue metastases and lung
      metastases), and three stable diseases. These studies confirm the possibilities
      of overcoming multidrug resistance by the administration of verapamil in tumor
      cells and in cancer patients.

PMID- 8873837
TI  - A phase II trial of etoposide, leucovorin and 5-fluorouracil (ELF) in patients
      with advanced gastric cancer.
AB  - Etoposide, leucovorin and 5-fluorouracil (ELF) chemotherapy has been reported to
      be less toxic yet effective (response rates of 50%) in patients with advanced
      gastric cancer. A phase II study of ELF in 25 patients (11 males, 14 females,
      median age 53 years) with advanced adenocarcinoma of the stomach is reported.
      Patients received outpatient intravenous etoposide 120mg/m2 over 2 hours, folinic
      acid 300 mg/m2 over 2 hours, 5-fluorouracil 500 mg/m2 boluses daily for 3 days
      every 21 days. Of 17 measurable patients, there was one complete response (CR), 4
      partial responses (PR) for a total response rate of 29.4%. Non-hematologic
      toxicity was modest (grade 0 vomiting 11/21, stomatitis 16/21, diarrhea 17/21).
      Grade 3/4 neutropenia was seen in 14/23, thrombocytopenia in 2/23, anemia in 5/23
      patients. Median progression-free and overall survival was 4.1 and 7.1 months,
      respectively. In conclusion, ELF chemotherapy shows only modest activity in
      patients with advanced gastric cancer and is associated with severe hematologic
      toxicity.

PMID- 8873839
TI  - Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast
      cancer.
AB  - The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16
      patients having advanced metastatic breast carcinoma as second-line chemotherapy.
      We observed complete response in 6%, partial response in 44% (total overall
      response rate of 50%), stable disease in 12% and progressive disease in the
      remaining 38% of the patients. The median remission duration in responders was
      calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile
      including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and
      neurotoxicity in which serious complications necessitating discontinuation of the
      chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy
      combination is an effective alternative among schedules in the management of
      patients with stage IV breast carcinoma without serious side effects.

PMID- 8873838
TI  - Modulation of cisplatin antitumor activity by short infusional high-dose cytosine
      arabinoside in advanced pretreated head and neck carcinoma: a phase II study.
AB  - The aim of the present study, which included 24 pretreated patients (both with
      radiotherapy and/or cisplatin-containing chemotherapy) with histological grade
      I/II head and neck cancer, was to investigate whether the enhancing action of
      cytosine arabinoside on cisplatin antitumor activity might be evidenced without
      excessive hematological toxicity with the administration of short infusional high
      dose cytosine arabinoside, applied before cisplatin. Cytosine arabinoside was
      administered on day 1 of the treatment cycle at 0h and 12h at the dosage of 500
      mg/m2 (1 hour infusion), and cisplatin at 6h and 18h of the same day with a dose
      of 20 mg/m2. On days 2, 3 and 4, only cisplatin 30 mg/m2/24h was administered. 19
      patients were evaluable for activity including 14 patients pretreated with
      cisplatin-containing chemotherapy. 2/19 achieved complete response (CR), 2/19 a
      partial response (PR), 8/19 had stable disease and 7/19 progressive disease.
      Objective responses (2 CR and 1 PR) were evidenced in 3/14 patients previously
      resistant to cisplatin at the same dosage as in the present regimen. WHO grade IV
      toxicity for granulocytes was recorded in only one patient.

PMID- 8873840
TI  - Single 8 mg dose of oral ondansetron failed to prevent FAC chemotherapy-induced
      acute nausea and vomiting.
AB  - The aim of this open, nonrandomized, monocentric study was to evaluate the
      efficacy of a single daily dose of 8 mg oral ondansetron in the prophylaxis of
      acute nausea and vomiting in chemotherapy-naive breast cancer patients receiving
      their first cycle of chemotherapy with 5-fluorouracil, doxorubicin and
      cyclophosphamide (FAC). Forty-five female patients were recruited, median age 42
      years. The number of emetic episodes and the grade of nausea were recorded. 51%
      of patients achieved complete, and 9% major control of acute emesis. 33% of
      patients experienced no acute nausea, and in 18% nausea was mild. Complete
      protection from nausea and vomiting (complete prophylaxis) was obtained in 12/45
      (27%) of patients. Treatment success (no vomiting with no more than mild nausea)
      was achieved in 18/45 (40%) of patients. We conclude that the efficacy of a
      single dose of 8 mg oral ondansetron in controlling acute nausea and vomiting
      induced by FAC chemotherapy is not high enough to justify its use as a sole
      antiemetic agent in outpatients.

PMID- 8873841
TI  - Surgery and polychemotherapy of non-functional endocrine pancreatic tumors: a
      case report with a dramatic clinical response.
AB  - Endocrine pancreatic tumors (EPT) are a rare clinical entity, representing 5% of
      all pancreatic tumors. Nonfunctional subtypes (NF-EPT) often present themselves
      at diagnosis in a locally advanced or metastatic stage. Therapeutic planning of
      these neoplasias is based on a multidisciplinary integration of surgery and
      medical treatments. The Authors describe a case of NF-EPT with massive metastatic
      spread after cytoreductive surgery, with impressive response to polychemotherapy
      with 5-fluorouracil, epirubicin and dacarbazine. The various options concerning
      chemotherapic treatment of these tumors are reviewed.

PMID- 8873842
TI  - First report of vancomycin-resistant Streptococcus mitis bacteremia in a leukemic
      patient after prophylaxis with quinolones and during treatment with vancomycin.

PMID- 8873843
TI  - Angiotensin receptor antagonists--a new class of antihypertensive drug.

PMID- 8873844
TI  - Social reform and violence: the case of the American prohibitionists.

PMID- 8873845
TI  - Tacrolimus: immunosuppression following liver and kidney transplant.
AB  - Advances in transplantation have been impressive since the introduction of
      cyclosporin, however, there is still considerable debate on the most suitable
      immunosuppressant regimen. Tacrolimus, a new macrolide immunosuppressant, was
      marketed in the U.K. in 1994. Open studies have demonstrated its equal efficacy
      to cyclosporin in terms of patient and graft survival rates when used for primary
      immunosuppression following both liver and kidney transplantations. Tacrolimus
      also provides a valuable alternative for patients experiencing rejection in whom
      re-transplantation is often the only alternative. Unfortunately, in the studies
      to date, tacrolimus use was associated with increased nephrotoxicity and
      neurotoxicity compared to cyclosporin. Further trials are therefore required to
      define tacrolimus' true value in this complex field.

PMID- 8873846
TI  - Vitamin D analogues and psoriasis.
AB  - Over recent years there has been increasing interest in the effects of vitamin D3
      and its analogues upon the skin, with particular relevance to the treatment of
      psoriasis. As well as offering an alternative therapeutic option, research into
      the mode of action of vitamin D3 upon the psoriatic lesion has provided insight
      into the pathogenesis of psoriasis. This article reviews the effects of vitamin
      D3 and its analogues upon normal skin and on psoriasis.

PMID- 8873847
TI  - Stability of radiopharmaceuticals during administration to the intensive care
      patient.
AB  - Nuclear medicine can provide useful data when monitoring the organ function of
      patients undergoing intensive care. Test procedures involve the administration of
      radiopharmaceuticals and external monitoring using gamma cameras or nuclear
      probes. The radiopharmaceuticals required may be given at lower doses than
      normally used in routine nuclear medicine imaging, are ideally available 24 h a
      day and are preferably administered via indwelling cannulae and giving sets.
      Three radiopharmaceuticals have been studied; a renal function agent, a
      hepatobiliary function agent and a product used for in vivo labelling of protein
      for lung permeability studies. Under conditions of storage, dilution and passage
      through giving sets (simulating conditions found during administration in the
      intensive care setting), some instability can be demonstrated in each product,
      which could result in the tests giving rise to wrong or misleading data. It is
      recommended that radiopharmaceuticals are not diluted excessively, and that where
      possible, parenterally-administered products are given by direct intravenous
      injection and not through giving sets.

PMID- 8873848
TI  - Effect of tablet integrity on the dissolution rate of sustained-release
      preparations.
AB  - The objective of this study was to evaluate the effect of tablet integrity on the
      dissolution rate. The model drug used for this study was aspirin. A dissolution
      study was performed with three commercially-available aspirin tablets (ZORprin,
      Bayer 8-h aspirin and Bayer aspirin), two of which were sustained-release
      tablets. For ZORprin, the average dissolution data indicated that the in vitro
      release rate of aspirin was consistent with the intended design of the sustained
      release wax matrix tablets only when the tablets were intact. The split tablets
      showed a consistently higher release profile over time, with a 50% higher release
      at 6 h. However, the Bayer 8-h aspirin and plain aspirin tablet data showed that
      tablet integrity had no significant impact on the dissolution rate, because the
      intact and split tablets showed similar drug release profiles over time. In
      conclusion, care should be taken to administer sustained-release tablets,
      avoiding any breaking or crushing of the tablets unless this is directed by the
      manufacturer.

PMID- 8873849
TI  - Assessment of nurses' judgement for analgesic requirements of postoperative
      children.
AB  - Over the last 5-10 years, there has been significant growth in the knowledge and
      strategies of pain management in children. Investigations are required to discern
      whether concomitant improvements in clinical practice have occurred. The purpose
      of this study was to identify the nurses' administration of a traditional
      analgesic (acetaminophen) with regard to appropriate doses and time intervals.
      This issue was examined, within 24 h after surgery, in 72 children (aged 3-12
      years) scheduled for a tonsillectomy. Acetaminophen suppositories were
      administered in subtherapeutic doses and at too large time intervals. An average
      single dose administered represented 87% of the calculated dose. Comparison
      between the correct dose, which should have been given considering the dose
      levels of the suppositories available, and the actual dose administered indicates
      that the nurses tended to round doses down to the next lowest. The average dosage
      administered per day represented only 76% of the recommended dosage. The
      prevalence of pain amongst the children was high both before and after
      analgesics, indicating that acetaminophen in the doses used did not provide any
      significant measure of pain relief. Current practice is still not optimal.
      Educating nurses on the effective use of traditional pain therapies may improve
      paediatric pain management.

PMID- 8873850
TI  - Effect of dialysis on exogenous dopamine in haemodialysed critically ill
      patients.
AB  - A sensitive and specific high performance liquid chromatographic method (HPLC)
      was developed for measuring dopamine (DA) in human plasma samples.
      Dihydroxybenzylamine (DHBA) was employed as an internal standard. Following
      solvent extraction and separation on a C18 ion-pairing reversed phase column, the
      drug was detected by a fluorescence detector with excitation and emission
      wavelengths of 233 nm and 345 nm, respectively. This method was employed to
      evaluate dopamine dialysability in seven haemodialysed patients under continuous
      infusion of a positive inotropic agent. Results showed a high dialyser extraction
      ratio averaging 38.3%, but a low dialysis clearance of 67 ml/min. The fraction
      removed by dialysis is 2.5%. We concluded that haemodialysis has little effect on
      dopamine blood levels, and consequently on drug pharmacokinetics, when the drug
      is delivered to haemodialysed patients under intravenous infusion.

PMID- 8873851
TI  - Chemical stability and adsorption of atracurium besylate injections in disposable
      plastic syringes.
AB  - Atracurium besylate (AB) is supplied as a sterile, non-pyrogenic aqueous solution
      for intravenous use. Hospitals pre-fill disposable plastic syringes with these
      solutions so that they are ready for immediate use when required. Drug loss due
      to potential adsorption on to the plastic material of the syringes has not been
      studied. Atracurium is also administered by intravenous infusion using a diluted
      solution in either 5% dextrose injection (USP) or 0.9% sodium chloride injection
      USP. Drug solutions not used within 24 h are usually discarded, resulting in
      tremendous waste. The purpose of these investigations was to determine the
      adsorption behaviour of atracurium when stored in plastic syringes, and to study
      the degradation of atracurium in i.v. fluids. For the adsorption study, 10 mg/ml
      solutions were used, whereas the diluted infusion solutions were prepared to
      contain 0.5 mg/ml of atracurium. Drug degradation was monitored using a stability
      indicating high-performance liquid chromatography method. Degradation studies
      were conducted at 5 degrees C, 25 degrees C and 40 degrees C. Refrigeration was
      observed to improve drug stability. The manufacturer's recommended expiry period
      was too conservative. Storage at room temperature for up to 6 weeks can be safely
      recommended, without significant loss of chemical stability.

PMID- 8873852
TI  - Pharmacy consultation and over-the-counter medication purchasing outcomes. Over
      the-Counter Medication Intervention Project Team.
AB  - A demonstration project was conducted within 23 community pharmacies located
      throughout the state of Washington to: (1) assess the effects of pharmacy
      consultation on over-the-counter (OTC) medication purchasing decisions and costs,
      (2) to identify factors influencing those intending to purchase a brand name
      medication to change to a generic or private label product, or to a different
      brand name product, and (3) to quantify prevented adverse medication outcomes.
      Pharmacy students in their final year of training provided consultation to 745
      consumers intending to purchase an OTC product. The consultations averaged 4.6
      min in length, and resulted in 42.6% of consumers changing their intended
      purchase. These changes reduced OTC expenditures by an average of US $1.53 per
      customer, primarily as a result of movement from brand name products to lower
      priced generic or private label equivalents. Nearly 8% of consumers made no
      purchase after consultation, and 4.3% were referred to a physician. Logistic
      regression analysis identified gender of the consultant being female (odds ratio
      = 3.87, 95% CI = 1.58-9.45), and an increasing length of consultation (odds ratio
      = 1.30, 95% CI = 1.08-1.57) as being significant factors influencing consumers to
      change their final purchase from a brand name OTC product to a generic or private
      label, or to a different brand name product. Potential adverse outcomes (disease
      medication interaction; medication-medication interaction; additive side-effects;
      or duplication in therapeutic category) were prevented in 7.1% of the study
      population. This study documents consumer need for pharmacy consultation in order
      to optimize both the therapeutic appropriateness of, and pharmaceutical
      expenditures for OTC medication.

PMID- 8873853
TI  - Long-term stability of cefuroxime and cefazolin sodium in intravenous infusions.
AB  - Cefazolin and cefuroxime sodium are often used as antibiotic infusions for
      hospitalized patients. Because advance preparation of these intravenous solutions
      is efficient, the stability of both antibiotics stored at 4 degrees C in
      polyvinyl chloride (PVC) bags was studied. Five bags of solutions containing
      either 1 g of cefazolin sodium or 1.5 g of cefuroxime sodium per 100 ml of 5%
      dextrose were studied for 1 month by high-performance liquid chromatography
      (HPLC), visual inspection and pH measurement. No colour change or precipitation
      was observed. The pH values of both drugs increased significantly over the period
      of study. Based on a shelf-life of 90% residual potency, the cefuroxime sodium
      concentration was stable for 13 days when stored at 4 degrees C, and the
      cefazolin sodium concentration was stable for at least 30 days at 4 degrees C.
      Within these limits, both antibiotics may be prepared in advance by a centralized
      intravenous admixture service.

PMID- 8873854
TI  - Prenatal diagnosis with ultrasound of anomalous course of the umbilical vein and
      its relationship to fetal outcome.
AB  - Diagnosis of three types of anomalous course of the umbilical vein (UV) was made
      in 10 cases using antenatal ultrasound (US). Pulsed wave (PW) Doppler ultrasound
      was used to evaluate the UV in all cases. In one case, the UV was directly
      joining the superior vena cava (SVC) without forming subcutaneous collaterals, an
      abnormal course of UV not yet reported previously. Of these ten fetuses, six had
      various associated anomalies, including three fetuses with central nervous system
      (CNS) abnormalities.

PMID- 8873855
TI  - Urachal remnants: sonographic assessment.
AB  - OBJECTIVE: To evaluate the frequency of the visualization of urachal remnants
      (UR) with ultrasound and to determine their sonographic patterns. SUBJECTS AND
      METHODS: Two hundred and fifty consecutive patients were referred for abdominal
      and/or pelvic ultrasonography, 83 who had urinary tract symptoms. Patient age
      ranged from 1 month to 91 years (mean = 35 years). Patients were classified into
      four groups: (1) < 16 years (n = 47) (2) 16-35 years (n = 100), (3) 36-55 years
      (n = 49), (4) > or = 56 years (n = 54). Ultrasonography was performed using 3.75
      MHz and 7.5 MHz transducers. Ultrasound criterion for diagnosis was a midline
      mass located between the rectus abdominus muscle and the upper part of the
      anterior bladder wall. RESULTS: UR were found in 90 cases (36%). UR demonstration
      was more frequent in groups 1 (61.7%) and 2 (49%) and 3 (20.4%) and 4 (3.7%). UR
      were nodular (87%) or tubular in structure (13%). Echogenicity was similar to or
      greater than adjacent muscle in 51% and less than in 49%. The length, width, and
      thickness mean and standard deviation values were 13.5 +/- 4.7 mm, 12.6 +/- 5 mm,
      and 5.2 +/- 1.5 mm, respectively. UR were observed in 50% of the asymptomatic
      patients of groups 1 and 2. CONCLUSION: Urachal remnants are commonly
      demonstrated with ultrasound, particularly in young patients. They should be
      considered to be a normal variant unless there is an increase in size or they are
      accompanied by clinical signs, without other possible causes for symptoms.

PMID- 8873856
TI  - Natural history of focal nodular hyperplasia of the liver: an ultrasound study.
AB  - Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by
      ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the
      diagnosis was incidental. On US the lesions were single in 75% of the cases,
      localized in the right lobe in 75%, and subcapsular in 50%. No specific US
      pattern could be identified. A central scar was found in 19% of the patients. At
      the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the
      lesion disappeared. The spontaneous reduction of nodules in FNH must be
      considered in the management of this pseudotumor.

PMID- 8873857
TI  - Transvaginal ultrasonographic measurements of endometrial thickness: a
      reproducibility study.
AB  - OBJECTIVE: The study was undertaken to assess the reproducibility of endometrial
      thickness measurements by transvaginal ultrasonography (TVS). METHODS: In a
      prospective blind study, two examiners measured the endometrial thickness of 25
      patients by TVS on two separate occasions 30 minutes apart. RESULTS: The
      reliability test performed for each examiner was statistically less significant
      for the intra-observer variation of each observer (r = 0.95 and r = 0.93), than
      between both examiners (r = 0.85). Although there was no statistically
      significant difference between the observations, the mean range of observations
      was 2.12 + 1.27 mm. CONCLUSIONS: A safety margin of error should be taken into
      consideration while recommending a cutoff under which no curettage is needed.

PMID- 8873858
TI  - Sonographic evaluation of the wall thickness of the lower uterine segment in
      patients with previous cesarean section.
AB  - In pregnant women with a history of cesarean section, wall thickness of the lower
      uterine segment may help determine the risk and safety of vaginal delivery.
      Determination of wall thickness may help identify the potential risk of uterine
      rupture in pregnant women who do not wish to have another cesarean section or who
      are not eligible for surgery due to other systemic disorders. In this study, 50
      pregnant women with previous cesarean sections were evaluated with ultrasound
      preoperatively, and measurements of the lower uterine segment wall thickness were
      compared with intraoperative assessment of uterine thinning. These findings
      correlated highly with each other (sensitivity: 100%; specificity: 82% positive
      predictive value: 87%; negative predictive value: 100%), suggesting the
      reliability and safety of ultrasound in evaluating uterine wall thickness.

PMID- 8873859
TI  - Paraumbilical venous collateral circulations: color Doppler ultrasound features.
AB  - Using Color Doppler ultrasonography to trace the dilated paraumbilical vein to
      its connection with systemic veins in 27 patients, we have found four major
      pathways: In type 1 (63%), the vein connected with the external iliac vein via
      the inferior epigastric vein. In type 2 (3.7%), the vein connected with the
      saphenous vein via the superficial epigastric vein. In type 3 (22.2%), the vein
      connected with the internal thoracic vein via the superior epigastric vein. Type
      4 (11.1%) is a combination of types 1 and 2. A frank caput medusa was not seen,
      but occult caput medusa were seen in two patients. Turbulent flow was seen at the
      junction between inferior epigastric and external iliac veins, paraumbilical and
      superficial epigastric veins, and superficial epigastric and saphenous veins in
      some patients. Color Doppler ultrasonography is a convenient, noninvasive method
      for determining the course and associated hemodynamic changes in the
      paraumbilical collateral circulation.

PMID- 8873860
TI  - "Whirlpool sign": not always associated with volvulus in intestinal malrotation.

PMID- 8873861
TI  - Intra-testicular varicocele: gray-scale and Doppler ultrasound findings.

PMID- 8873862
TI  - Ultrasound diagnosis of para-testicular neoplasm.

PMID- 8873863
TI  - A large, nonfunctioning parathyroid cyst recurring after aspiration and
      subsequently cured by percutaneous ethanol injection.

PMID- 8873864
TI  - Development of connections within and between areas V1 and V2 of macaque monkeys.
AB  - We have investigated the development of intrinsic and interareal connections in
      areas V1 and V2 of the macaque monkey using postmortem transport of the
      lipophilic fluorescent tracer diI, applied to brains fixed at different pre- and
      postnatal ages. Intrinsic connections in the deep layers of V1 are evident on
      embryonic day 108 (E108), but are not robust in the superficial layers until
      around E118, when migration is largely complete. Both intrinsic horizontal
      projections and extrinsic projections to V2 initially have a continuous
      distribution. Patchy projections are first evident in V1 around E145, the same
      age at which cytochrome oxidase blobs appear, presumably signaling the
      differentiation of the blob-dominated and interblob-dominated streams in the
      primary visual cortex. The magnocellular-dominated stream becomes distinct at
      earlier stages (by E122), as judged by connectional and histochemical criteria.
      In area V2, intrinsic connections initially (at E108) involve only deep layer
      cells and do not have a clustered organization. By E130, superficial layer cells
      are involved and the V2 intrinsic connections have a patchy distribution; by
      E145, an adult-like pattern is present. The projection from V2 to V1 passes
      through an early stage (up to E133) of originating principally from deep layer
      cells, and thereafter originating from superficial as well as deep layers. We
      found evidence for changes in dendritic morphology during development. Most
      notably, at E118, many neurons in layer 6 which are involved in intrinsic or
      interareal connections have dendrites that extend well into the superficial
      layers, even into layer 1, a characteristic not reported in the adult.

PMID- 8873865
TI  - Ultrastructural quantitative analysis of glutamatergic and GABAergic synaptic
      terminals in the phrenic nucleus after spinal cord injury.
AB  - Quantitative analysis of electron microscopic postembedding immunochemically
      stained material indicates that 48% of all terminals in the rat phrenic nucleus
      are glutamatergic and 33% are gamma-aminobutyric acid (GABA)ergic. Three distinct
      types of glutamatergic terminals were observed in the rat phrenic nucleus:
      terminals characterized by large, loosely arranged spherical synaptic vesicles
      (SI) or small, compact spherical synaptic vesicles (Ss) and elongated terminals
      containing spherical synaptic vesicles with neurofilaments (NFs). All three types
      of glutamatergic terminals display asymmetrical synaptic membrane densities with
      postsynaptic dense bodies being present in some of the S-type terminals. The
      GABAergic immunoreactive terminals in the phrenic nucleus most closely resemble F
      type terminals. They are characterized by flattened or pleomorphic synaptic
      vesicles and symmetric synaptic membrane densities. Among the 48% glutamatergic
      terminals, 27% are SI, 65% are Ss, and 8% are NFs, respectively. Significantly
      fewer glutamate, GABA, and unlabeled terminals per unit area are present in the
      phrenic nucleus 30 days after a C2 spinal cord hemisection as compared to
      nonhemisected controls. The average number of active zones per terminal, however,
      is greater in the hemisection group (1.45 +/- 0.03) than in the control group
      (1.34 +/- 0.03), with the active zones in the glutamate terminals mainly
      accounting for this difference. Moreover, the length of the active zones in the
      glutamate terminals was significantly longer in the hemisection group (0.37 +/-
      0.013 microns) as compared to the controls (0.24 +/- 0.008 microns). In addition,
      the mean length of synaptic active zones in GABAergic terminals was also found to
      be longer in the hemisection group (0.36 +/- 0.022 microns) as compared to
      controls (0.28 +/- 0.014 microns). Finally, there is also a significantly higher
      ratio of synaptic active zones to the total number of glutamate-labeled terminals
      after injury (1.73 +/- 0.08) as compared to controls (1.41 +/- 0.04). The number
      of double/multiple synapses, the percentages of Sl, Ss, and NFs-type terminals,
      and the percentages of synaptic active zones contacting either distal dendrites
      or proximal dendrites/somata do not change significantly 30 days after injury.
      These results are important for a more complete understanding of the synaptic
      plasticity that occurs in the phrenic nucleus after spinal cord injury and to
      show how the plasticity may relate to the unmasking of latent bulbospinal
      respiratory connections which restore function to the hemidiaphragm paralyzed by
      an ipsilateral spinal cord hemisection.

PMID- 8873866
TI  - Ionotropic and metabotropic glutamate receptors show unique postsynaptic,
      presynaptic, and glial localizations in the dorsal cochlear nucleus.
AB  - The dorsal cochlear nucleus (DCN) is a major brain center for integration of
      auditory information, and excitatory amino acid neurotransmission plays a central
      role in the processing of this information. In this study, the distribution of
      glutamate receptors was examined with preembedding immunocytochemistry, using 14
      antibodies to ionotropic (GluR1, GluR2/3, GluR4, GluR5-7, GluR6/7, KA2, NR1,
      NR2A/B, delta 1/2) and metabotropic (mGluR1 alpha, mGluR2/3, mGluR5) glutamate
      receptor subtypes. Each of these antibodies produced a specific immunolabeling
      pattern, including a variety of postsynaptic, presynaptic, and glial
      localizations. Some antibodies showed widespread distribution patterns, notably
      the antibodies to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptor subunits, GluR2 and GluR3, and the N-methyl-D-aspartate (NMDA) receptor
      subunit, NR1. In contrast, antibodies to other glutamate receptor subunits
      produced more restricted distribution patterns, especially that to GluR1, which
      stained the outer neuropil of the DCN, cartwheel cells, and a small population of
      presumptive interneurons associated with the dorsal acoustic stria, but produced
      little or no staining in fusiform cells or deep DCN neurons. Staining of the
      postsynaptic density and membrane of the granule cell-parallel fiber/cartwheel
      cell spins synapse was most prevalent with delta 1/2 and mGluR1 alpha antibodies.
      A unique pattern of staining was found with mGluR2/3 antibody--with staining
      concentrated in Golgi cells and unipolar brush cells of the middle to deep DCN.
      Distribution of some glutamate receptors in the DCN shows similarities to that of
      the cerebellum, where delta 2 and mGluR1 alpha may modulate neurotransmission at
      parallel fiber synapses, while mGluR2 and/or mGluR3 may modulate mossy terminal
      function.

PMID- 8873867
TI  - Reciprocal entorhinal-hippocampal connections established by human fetal
      midgestation.
AB  - Little is known about the timing or sequence of genesis of connections between
      different areas of the developing human cerebral cortex. It has been shown that
      connections between areas V1 and V2 of the visual isocortex are established at
      about 37 weeks of gestation (Burkhalter [1993] Cerebr. Cortex 3:476-487),
      suggesting that cortico-cortical connections appear late in the 40-week human
      gestational period. However, there are indications from other studies that
      connections between subdivisions of the hippocampal formation may be established
      much earlier, by about 20 weeks of human gestation. To investigate this
      possibility, the lipophilic bidirectional tracer 1,1' dioctadecyl-3,3,3',3
      tetramethylindocarbocyanine perchlorate (DiI) was used to study connections
      between the entorhinal cortex, hippocampus, and temporal lobe neocortex in
      paraformaldehyde-fixed postmortem fetal tissue. The DiI transport revealed robust
      reciprocal connections between the entorhinal cortex, hippocampus, and subiculum,
      which were consistently present at 19 weeks of gestation (the earliest age
      studied), and which were anatomically similar to those in adult primates.
      Specifically, projections to the hippocampus and subiculum originated from
      neurons in the entorhinal cortex (EC) layers 2 and 3, whereas reciprocal
      projections to the EC originated from pyramidal neurons in the cornu ammonis
      region CA1 and the subiculum. In contrast, the perforant pathway projection from
      EC to the dentate gyrus, and all connections with the neocortex, reached only
      rudimentary stages of development by 22 weeks of gestation (the latest age
      studied). These findings suggest that hippocampal pathways develop prior to
      isocortical pathways, and that reciprocal entorhinal-hippocampal projections may
      be among the first cortico-cortical connections to be established in the human
      brain.

PMID- 8873868
TI  - In situ hybridization analysis of the distribution of neurokinin-3 mRNA in the
      rat central nervous system.
AB  - The tachykinin family of neuropeptides, which includes substance P, neurokinin A,
      and neurokinin B, have three distinct receptors: NK-1, NK-2, and NK-3. With the
      cloning of the rat NK-3 cDNA, it is now possible to evaluate the distribution of
      NK-3 mRNA in the rat brain. Female rat brains were sectioned and hybridized with
      a riboprobe complimentary to NK-3 mRNA. The results of these studies revealed an
      extensive distribution of NK-3 mRNA throughout the rostral-caudal extent of the
      brain, spinal cord, and retina. In agreement with previous binding studies, we
      observed NK-3 mRNA in the cortex, the amygdala, the hippocampus, the medial
      habenula, the zona incerta, the paraventricular and supraoptic nuclei of the
      hypothalamus, the substantia nigra, the ventral tegmental area, the
      interpeduncular nucleus, the raphe nuclei, the dorsal tegmental nucleus, and the
      nucleus of the solitary tract. In contrast with binding data, only a few NK-3
      mRNA cells were detected in the striatum. In addition, the present study detected
      NK-3 mRNA in the olfactory bulb, the dentate gyrus and subiculum, the medial
      septum, the diagonal band of Broca, the ventral pallidum, the globus pallidus,
      the bed nucleus of the stria terminalis, the arcuate, the premammillary and
      mammillary nuclei, the dorsal and lateral regions of the posterior hypothalamus,
      the central gray, the cerebellum, the parabrachial nuclei, the nucleus of the
      spinal trigeminal tract, the dorsal horn of the spinal cord, and the retina. The
      results of these in situ hybridization histochemical studies have provided
      detailed and novel information about the distribution of NK-3 mRNA and have
      elucidated the putative sites of neurokinin B action in the rat central nervous
      system.

PMID- 8873869
TI  - Remodeling of the peripheral processes and presynaptic terminals of leg
      motoneurons during metamorphosis of the hawkmoth, Manduca sexta.
AB  - During metamorphosis of the hawkmoth, Manduca sexta, the muscles, cuticular
      structures, and most sensory neurons of the larval thoracic legs are replaced by
      new elements in the adult legs. The thoracic leg motoneurons, however, survive
      the loss of the larval muscles and persist to innervate new targets in the
      imaginal legs. Here we have used biocytin staining, immunocytochemistry, and
      confocal microscopy to follow the fates of the peripheral processes and
      presynaptic terminals of the leg motoneurons. Although the most distal processes
      of the motor nerves retract following the degeneration of larval leg muscles, the
      axon terminals always retain close association with the muscle remnants and the
      anlagen of the new adult muscles. As the imaginal muscles differentiate and
      enlarge, the motor terminals expand to form adult presynaptic terminals. An
      antibody to the presynaptic protein, synaptotagmin, revealed its localization to
      the terminal varicosities in both larval and adult stages but distribution within
      pre-terminal branches during adult development. Electrophysiological methods
      revealed that functional neuromuscular transmission first occurs quite early
      during metamorphosis, before the differentiation of contractile elements in the
      muscle fibers.

PMID- 8873870
TI  - Attempts to facilitate dorsal column axonal regeneration in a neonatal spinal
      environment.
AB  - The response to injury of ascending collaterals of dorsal root axons within the
      dorsal column (DC) was studied after neonatal spinal overhemisection (OH) made at
      different levels of the spinal cord. The transganglionic tracer, cholera toxin
      conjugated to horseradish peroxidase, and the anterograde tracer, biotinylated
      dextran amine, were used to label dorsal root ganglion cells with peripheral
      axons contributing to the sciatic nerve. There was no indication of a
      regenerative attempt by DC axons at acute survival times (3 days and later) after
      cervical injury, replicating previous work done at chronic survival periods (Lahr
      and Stelzner [1990] J. Comp. Neurol. 293:377-398). There was also no evidence of
      DC regeneration after lumbar OH injury even though immunohistochemical studies
      using the oligodendrocyte markers Rip and myelin basic protein showed few
      oligodendrocytes in the gracile fasciculus at lumbar levels at birth. Therefore,
      the lack of myelin in the dorsal funiculus at lumbar levels does not enhance the
      growth of neonatally axotomized DC axons. In addition, DC axons did not
      regenerate when presented with fetal spinal tissue implanted into thoracic OH
      lesions, even though positive control experiments showed that segmental dorsal
      root axons containing calcition gene-related peptide and corticospinal axons grew
      into these implants, replicating previous work of others. When a thoracic OH
      lesion, with or without a fetal spinal implant, was combined with sciatic nerve
      injury to attempt to stimulate an intracellular regenerative response of DRG
      neurons, again, no evidence of DC axonal regeneration was detected. Quantitative
      studies of the L4 and L5 dorsal root ganglia (DRG) showed that OH injury did not
      result in DRG neuronal loss. However, sciatic nerve injury did result in
      significant post-axotomy retrograde cell loss of DRG neurons, even in groups
      receiving thoracic embryonic spinal implants, and is one explanation for the
      minimal effect of sciatic nerve injury on DC regeneration. Although fetal tissue
      did not appear to rescue a significant number of DRG neurons, the quantitative
      analysis showed an enlargement of the largest class of DRG neuron, the class that
      contributes to the DC projection, in all groups receiving fetal tissue implants.
      This apparent trophic effect did not affect DC regeneration or neuronal survival
      after peripheral axotomy. Further studies are needed to determine why DC axons do
      not regenerate in a neonatal spinal environment or within fetal tissue implants,
      especially because previous work by others in both the developing and adult
      spinal cord shows that dorsal root axons will grow within the same type of fetal
      spinal implant.

PMID- 8873871
TI  - Apparent apoptotic cell death in the olfactory epithelium of adult rodents: death
      occurs at different developmental stages.
AB  - In the olfactory epithelium of adult rodent, receptor neurons are generated
      continually. Despite the ongoing generation of new neurons, no corresponding
      increase occurs in the thickness of the mature olfactory epithelium. Thus,
      epithelial cell death must occur to offset the continual generation of new cells.
      In the present study, a sensitive method to label nicked DNA in dying cells was
      combined with immunocytochemistry to determine the identity of dying olfactory
      cells. In addition, the positions of putative apoptotic cells were mapped to
      provide additional information about the identity of dying cells. Double labeling
      experiments revealed that each of the olfactory cell types, i.e., basal cells
      (keratin-positive), immature neurons (GAP43-positive) and mature receptor neurons
      (olfactory marker protein (OMP)-positive), were positive for fragmented DNA,
      suggesting that they undergo apoptotic cell death. The results of the mapping
      study suggest that apoptotic cell death occurs primarily among GAP43-positive
      neurons.

PMID- 8873872
TI  - Horseradish peroxidase study of the spatial and electrotonic distribution of
      group Ia synapses on type-identified ankle extensor motoneurons in the cat.
AB  - Eight functionally identified group Ia muscle afferents from triceps surae or
      plantaris muscles were labeled intraaxonally with horseradish peroxidase (HRP) in
      seven adult cats. Subsequently, HRP was injected into two to six homonymous or
      heteronymous alpha-motoneurons per animal (total = 22), each identified by motor
      unit type and located near the site of afferent injection. The complete
      trajectories of labeled afferents were reconstructed, and putative synaptic
      contacts on HRP-labeled motoneurons were identified at high magnification.
      Dendritic paths from each contact were also mapped and measured. A total of 24
      contact systems (the combination of a group Ia afferent and a postsynaptic
      motoneuron) were reconstructed, of which 17 were homonymous, and seven were
      heteronymous. Overall, homonymous contact systems had an average of 9.6 boutons,
      whereas heteronymous contact systems had an average of 5.9 boutons. The average
      number of boutons found on type S motoneurons in homonymous contact systems was
      smaller (6.4, range 3-17) than in systems involving types FF or FR motoneurons
      (FF: 10.4, range 4-18; FR: 11.3, range 4-32). Neither of these differences were
      statistically significant. In contrast to earlier reports, a majority (15/24) of
      contact systems included more than one collateral from the same Ia afferent. The
      complexity (number of branch points) in the arborization pathway leading to each
      contact (overall mean 8.4 +/- 3.3) was virtually identical in all contact
      systems, irrespective of the type of postsynaptic motoneuron. The three
      dimensional distribution of group Ia contacts was not coextensive with the
      radially organized dendrites of motoneurons: Dendrites oriented in the
      ventromedial to dorsolateral axis had the fewest (8%) contacts, whereas
      rostrocaudal dendrites had the most (63%) contacts. Nevertheless, contacts were
      widely distributed on the motoneuron surface, with few on and near the soma (< or
      = 200 microns radial distance from the soma) or on the most distal parts of the
      tree (> or = 1,000 microns). The boutons in individual contact systems also
      showed wide spatial and estimated electrotonic distributions; only 3/24 systems
      had all contact located within a restricted spatial/electrotonic region. The
      relations between these anatomical results and existing electrophysiological data
      on group Ia synaptic potentials are discussed.

PMID- 8873874
TI  - My day with Luria.

PMID- 8873873
TI  - Pharmacologic treatment of agitation in dementia: a comprehensive review.
AB  - Agitated behaviors are a common and nearly universal occurrence among patients
      suffering from dementing illnesses. The pharmacologic treatments available for
      this troubling syndrome are varied, but treatment studies are limited. Clinicians
      are frequently faced with the challenging management of patients with disruptive
      behavior who fail to respond to trials with multiple agents. This review
      summarizes available treatment studies of agitation in dementia and offers a
      guide to therapy and management. Reports of therapies for agitation in dementia
      are limited by lack of controlled studies, variability of diagnostic criteria and
      outcome measures, and small sample size. The need for carefully designed, well
      controlled studies of outcome in this growing population is formidable. It is
      imperative to identify effective and well-tolerated treatment strategies to
      reduce the morbidity of these distressing and burdensome symptoms.

PMID- 8873875
TI  - Risk of mortality and institutionalization in demented patients with delusions.
AB  - Delusions are a common symptom during the course of dementia. Despite their
      clinical relevance, however, it is still unclear whether they are of prognostic
      value. This longitudinal study involving, at baseline, 99 demented Alzheimer
      disease (AD) and multi-infarct dementia (MID) patients, investigates the risk of
      mortality and institutionalization at 2 years after discharge from a dementia
      unit in patients with and without delusions at baseline. Results indicate that
      the presence of delusions is a significant predictor of future
      institutionalization (odds ratio 3.6, confidence interval 1.3-9.6), even when
      confounding factors such as age, educational level, and severity of cognitive and
      functional impairment are statistically controlled. No significant impact on
      survival was found.

PMID- 8873876
TI  - Screening African-American elderly for the presence of depressive symptoms: a
      preliminary investigation.
AB  - Several authors have reported that older African-Americans with multiple medical
      problems and decreased activities of daily living are at an increased risk of
      reporting symptoms of depression. African-Americans were more likely to report
      symptoms of anger, irritability, denial of illness, and to spontaneously report
      symptoms that did not reflect a change in mood, but rather forbearance of a
      difficult time or somatic complaints. This paper describes the results of a study
      to assess the presence of depressive symptoms in older African-American community
      residents. A new instrument, the Baker Belief Scale, is compared with the Center
      for Epidemiologic Studies-Depression Scale (CES-D) and the association of medical
      illnesses, social network, and level of physical function in activities of daily
      living (ADL). Ninety-six African-American men and women, aged 60 years or older,
      with equal representation from urban and rural counties in western Tennessee
      comprised the sample. The sample was stratified, in each of the two counties,
      into three age categories; 60-69, 70-79, and 80 years and older. A screening
      battery consisting of the Short Portable Mental Status Questionnaire, the CES-D,
      the Lubben Social Network Scale, and the Katz ADL were administered to the
      sample. Current medical illnesses were recorded with demographic data. There was
      a significant association between the CES-D score and the BBS score for those who
      screened positive for symptoms of depression. In addition there was a significant
      relationship between CES-D score and specific medical illnesses, social network,
      physical function in ADL, and residence (urban vs. rural). Residents who screened
      positive (N = 19) for depressive symptomatology with CES-D scores of 16 or higher
      exhibited a higher frequency of hypertension, arteriosclerosis, and circulatory
      problems than those who tested negative (N = 77). More urban residents (N = 13)
      than rural residents (N = 6) screened positive for symptoms of depression.
      Approximately 21% (N = 20) of the 96 respondents had scores of 20 or less on the
      Lubben Social Network Scale, suggesting a group of "at risk" for social
      isolation.

PMID- 8873877
TI  - Drug-induced Parkinsonism associated with dysphagia and aspiration: a brief
      report.
AB  - Idiopathic Parkinsonism is a well-recognized cause of dysphagia and resultant
      aspiration. Symptoms and signs attributable to dopaminergic underactivity after
      administration of antipsychotic medication are commonly seen in elderly patients.
      We report a case of a 74-year-old woman, without prior symptoms of Parkinsonism
      or dysphagia, who presented with the temporal association of both after
      administration of trifluoperazine hydrochloride. Dysphagia is a potentially life
      threatening complication of drug-induced parkinsonism. Its early recognition
      allows treatment by simple medical, physical, and dietary manipulations.

PMID- 8873878
TI  - Effects of normal aging on the performance of motor-vehicle operational skills.
AB  - Operational skills involved in controlling a motor vehicle were measured in two
      groups of very healthy elderly drivers and a young control group to test the
      hypothesis that there are age-related declines in operational performance that
      may influence driver safety. An actual behind-the-wheel, standardized road test
      was employed using a motor vehicle equipped with sensors to record speed, braking
      activity, and lane position, as well as direction and magnitude of front-wheel
      and eye-movement excursions. The data from these sensors were used as dependent
      measures of operational performance. Older drivers made fewer steering and eye
      movement excursions and drifted across the center line more frequently than the
      young control group. Younger drivers drove significantly faster and executed more
      braking applications than did their older counterparts. The motor-vehicle
      operational performance of older healthy drivers was related to visual-spatial
      attentional declines and the useful field of vision associated with the normal
      aging process.

PMID- 8873879
TI  - Antiandrogen treatment of aggressivity in men suffering from dementia.
AB  - Three demented patients who manifested an aggressive syndrome and motor
      disturbances including agitation, pacing, and restlessness received a therapeutic
      trial of the antiandrogen agents medroxyprogesterone acetate and luprolide
      acetate. Within 4 weeks of the start of the antiandrogen therapy, verbal and
      physical aggressivity had ceased; activity disturbances such as agitation,
      pacing, and restlessness were markedly reduced. One patient also manifested
      marked disinhibited and disruptive sexual behavior. Following treatment, that
      behavior also ceased. Further control studies assessing the efficacy and safety
      of antiandrogen agents are recommended.

PMID- 8873880
TI  - A case of late-onset psychosis: integrating neuropsychological and SPECT data.
AB  - We report the case of a 67-year-old woman who experienced a sudden onset of
      psychotic illness (i.e., prominent delusions and hallucinations) that has endured
      for approximately 3 years. As part of her neurobehavioral work-up, a SPECT scan
      revealed right frontal and left anterior temporal-lobe hypoperfusion. Serial
      neuropsychological evaluations obtained 2 years apart demonstrated a steady
      decline on tests of executive control (monitoring, allocation of attention,
      perseveration) and visuospatial abilities, whereas performance in other areas of
      cognitive functioning have remained steady and in the normal range for the
      patient's age. Over this same period of time, serial EEG, MRI, and neurology
      examinations have been within normal limits. Thus, there was little evidence with
      which to diagnose dementia. It is suggested that concomitant impairment in
      executive control, coupled with a degraded capacity to process perceptual
      information, can give rise to enduring psychotic behavior.

PMID- 8873881
TI  - Pneumocystis carinii: an atypical fungal micro-organism.
AB  - The purpose of this review is to assist mycologists in having a better
      understanding of Pneumocystis carinii and the disease that it causes. Now
      considered to be a fungus, P. carinii is unusual in its life cycle and
      relationship with the host. P. carinii pneumonia (PCP) pathogenesis, immunology
      and host defence mechanisms are examined, as well as epidemiological and control
      strategies. Most pneumocystosis pathophysiological changes result from the
      parasite's attachment and proliferation in the lungs, resulting in a filling of
      the alveoli with masses of the micro-organism. Pathological changes include an
      increase in alveolar capillary membrane permeability and injury to the alveolar
      epithelium, which may be mediated by the release of degradative enzymes from the
      pathogen. A host response takes place by hypertrophy, and hyperplasia involving
      type II epithelial alveolar cells. P carinii interacts with pulmonary surfactants
      by binding to the hydrophilic proteins A and D, and by modifying their
      phospholipid composition. Alveolar macrophages and CD4+ T cells play a key role
      in the host's defence against Pneumocystis. The epidemiology of PCP remains
      poorly understood. Airborne transmission has been established, but the actual
      infective form and its source remains unknown. Studies concerning P. carinii
      genetic diversity have shown that the parasite polymorphism is related, at least
      partially, to the host species. A strong host-species specificity in P. carinii
      has been found. From an epidemiological perspective, there appears to be no
      animal reservoir for the agent of human PCP. Thus, this disease should not be
      considered to be zoonotic. Although a significant decrease in the incidence of
      pneumocystosis has been obtained when employing chemoprophylaxis, anti-P. carinii
      drugs are not completely successful, often inducing deleterious side-effects. For
      these reasons, new prophylactic and therapeutic strategies need to be developed.
      One approach could be based on the anti-P. carinii effect of yeast killer toxins
      and antibiotic anti-idiotypic antibodies.

PMID- 8873882
TI  - Therapy of systemic histoplasmosis in immunosuppressed mice with the triazole
      D0870.
AB  - Because histoplasmosis is a life-threatening disease in AIDS and other
      compromised patients, we examined the efficacy of D0870 (Zeneca) in
      immunosuppressed mice against systemic histoplasmosis. Oral therapy with
      fluconazole given once daily (QD) was ineffective in prolonging survival, whereas
      itraconazole given once or twice daily (BID), fluconazole given BID or D0870
      given QD or given every other day (QOD) were efficacious (P < 0.001). Burdens of
      Histoplasma capsulatum in the liver and spleen of survivors showed that D0870
      given QD or QOD and itraconazole given BID caused dose-responsive reduction of
      infectious burden. Infection was cleared more readily from the liver than from
      the spleen. Overall, D0870 was > or = 20-fold more efficacious than fluconazole
      or itraconazole and itraconazole was > ten-fold better than fluconazole for the
      treatment of systemic histoplasmosis in the immunosuppressed model.

PMID- 8873883
TI  - Cycloactive, aneugenic and clastogenic effects of Paracoccidioides brasiliensis
      exoantigen in human lymphocyte cultures.
AB  - The in vitro effect of Paracoccidioides brasiliensis exoantigen on the human
      lymphocytes cell cycle and chromosomes was studied. Human peripheral blood
      lymphocyte cultures from ten healthy, white, non-smoking, non-related adult males
      (mean age 31.3 +/- 8.2 years) were studied. Blood cultures were treated with
      three exoantigen concentrations (0.25, 2.50 and 10.00 micrograms ml-1). At least
      1000 metaphases were analysed at each concentration, for evaluation of numerical
      and structural chromosome aberrations (CA) and 30,000 for mitotic index (MI).
      Among the treated cultures, statistically significant differences in the
      frequencies of MI and CA were not observed. Nevertheless, when compared with
      control cultures, they all showed a significantly lower frequency of MI and
      higher frequency of CA. It is suggested that the detected alterations were caused
      by the exoantigen, its fractions or its metabolites.

PMID- 8873884
TI  - Assessment of a PCR technique for the detection and identification of
      Cryptococcus neoformans.
AB  - The 18S ribosomal RNA gene of Cryptococcus neoformans was amplified by polymerase
      chain reaction (PCR). The primers CPL1 and CPR4 were tested for their ability to
      amplify DNA from 30 strains of C. neoformans and 27 specimens of cerebrospinal
      fluid (CSF) from patients with cryptococcal meningitis. A 343 bp product was
      obtained and its specificity confirmed by Southern hybridization with an internal
      sequence (INSR4) probe. The sensitivity was 100 fg by Southern analysis and 1 pg
      using the PCR. Neither human nor a variety of other fungal and bacterial strains
      (n = 78) gave an amplified product. This PCR method can detect as few as 5 cells
      ml-1 of C. neoformans in spiked-CSF following a simple processing procedure. The
      developed system of PCR was more sensitive than the culture method and revealed a
      very high specificity. The PCR was easy to perform and needed only 4 h for all
      processes from receiving the CSF to detection of a specific DNA band after
      agarose gel electrophoresis. This would provide another rapid laboratory method
      for the diagnosis of cryptococcal meningitis.

PMID- 8873885
TI  - Colony phenotype switching in clinical and non-clinical isolates of Saccharomyces
      cerevisiae.
AB  - During studies on the virulence and genetics of isolates of Saccharomyces
      cerevisiae we noted colony phenotype switching. Virulent clinical (YJM128,
      YJM436) and avirulent non-clinical (Y55, YJM237) isolates of S. cerevisiae were
      scored for colony phenotypes and reversion rates of the switched second
      generation colonies on YEPD with phloxine B. YJM128 produced six colony
      phenotypes; 99.7% were large (8-9 mm diameter), smooth, pink with a white edge
      (type A) and the other five types arose at frequencies ranging from 2 x 10(-3) to
      5 x 10(-5). On replacing of type A, 98.8% of colonies scored arose as type A,
      1.1% type J and 0.1% larger, but similar to type A indicating both stability and
      reversibility. YJM436 also varied, with 91.3% arising as a single phenotype; five
      other phenotypes were observed at frequencies ranging from 7.6 x 10(-2) to 1.5 x
      10(-4). For Y55, 0.2% of the colonies were 5-7 mm in size with a ridged pink edge
      (type D); 36.4% of YJM237 were a 5-7 mm, smooth pink colony (type H). The
      remaining 99.8% of Y55 and 63.4% of YJM237 colonies arose as sectored or non
      sectored non-reverting petites. These results indicate that virulent isolates of
      S. cerevisiae tend to produce multiple colony phenotypes, which are reversible.
      In contrast, avirulent isolates of S. cerevisiae showed single colony phenotypes
      and a high frequency of non-reverting petites. Whether selected colony phenotypes
      and switching are associated with the virulence of S. cerevisiae remains to be
      determined.

PMID- 8873886
TI  - Evaluation of Paracoccidioides brasiliensis exoantigen in the detection of
      delayed dermal hypersensitivity in experimental and human paracoccidioidomycosis.
AB  - The exoantigen of Paracoccidioides brasiliensis standardized by Camargo et al.
      (AgR) was used to evaluate the in vivo and in vitro cell immune response of
      experimental animals and of patients with paracoccidioidomycosis (PBM). Fava
      Netto antigen (AgF) was tested in parallel as a control antigen. The study was
      conducted with mice and guinea pigs infected with P. brasiliensis or immunized
      with its fungal antigens, on patients with PBM and on their respective control
      groups. The cell immune response was analysed by skin tests, and by the
      macrophage and leucocyte migration inhibition tests (MMIT and LMIT) in the
      animals and in the patients, respectively. The skin test with AgR as
      paracoccidioidin was positive in infected or immunized mice and guinea pigs and
      negative in control animals. The skin tests with AgR (24 h) showed 96.7%
      positivity in patients with PBM and were negative in control individuals.
      Histopathological study of the in vivo tests in the different experimental models
      was consistent with a delayed hypersensitivity response (DHR).
      Immunohistochemical study of the skin tests of PBM patients demonstrated a
      predominance of T lymphocytes, confirming the nature of a DHR to the fungal
      antigens. The in vitro cell immune response showed variable results for the
      various experimental models, i.e. significant rates of MMIT in immunized mice, a
      tendency to positivity in infected guinea pigs, and the absence of migration
      inhibition in PBM patients. Taken together, the data indicate that the AgR is
      efficient as paracoccidioidin in the evaluation of DHR in PBM, with an optimum
      time of reading the test of 24 h.

PMID- 8873887
TI  - Specific components found in circulating immune complexes (CIC) in
      paracoccidioidomycosis.
AB  - Circulating immune complexes (CIC) from 15 paracoccidioidomycosis (PCM) patient
      sera and from 20 healthy control sera were analysed. After CIC precipitation,
      solubilization and acid treatment, only a little reactivity to P. brasiliensis
      antigens was found in the free antibodies from PCM-CIC. This result has suggested
      that there were antibodies with a high affinity bound to fungus components.
      Dissociated CIC were fractionated in a column of Sephacryl S300 and the fractions
      that probably contained antigens were pooled and applied to an affinity column,
      prepared with mouse anti-gp43 monoclonal antibody. Using ECL-Western blotting
      assay two polypeptide with apparent mass of 43 and 62 kDa were found.

PMID- 8873888
TI  - Lasiodiplodia theobromae isolated from a subcutaneous abscess in a Cambodian
      immigrant to Australia.
AB  - A patient from Cambodia presented at a hospital in Melbourne with a persistent
      subcutaneous abscess of the right buttock. Septate fungal hyphae were seen in
      biopsy tissue. Lasiodiplodia theobromae was isolated and identified by the
      formation of pycnidia that produced typical conidia. The abscess was managed by
      drainage and debridement only. We briefly review the history and importance of
      the fungus as a wound parasite in tropical horticulture and its relatively rare
      occurrence in human infections. The significance of this fungus in Australian
      horticulture and its potential as an opportunistic human pathogen is noted. This
      paper records the first isolation of L. theobromae from a human lesion in
      Australia and the second isolation from a subcutaneous lesion worldwide.

PMID- 8873889
TI  - Trichophyton tonsurans tinea capitis in the San Francisco Bay area: increased
      infection demonstrated in a 20-year survey of fungal infections from 1974 to
      1994.
AB  - Tinea capitis caused by Trichophyton tonsurans has been increasing in the United
      States for the past 25 years. A retrospective study of dermatophyte culture data
      at the University of California, San Francisco, and a parallel study of patient
      visits for tinea capitis at an affiliated hospital demonstrates a dramatic rise
      in Trichophyton tonsurans tinea capitis in the San Francisco Bay area.

PMID- 8873890
TI  - Discordant regulation of phenoloxidase and capsular polysaccharide in
      Cryptococcus neoformans.
AB  - We examined the regulation of two fungal virulence factors, phenoloxidase and
      capsular polysaccharide, in an ex-type strain of the fungal pathogen,
      Cryptococcus neoformans. Both were made during the stationary phase of cultural
      growth. Exogenous iron increased phenoloxidase activity three-fold (from 8.7 to
      27.7 units mg-1, P < 0.05) but decreased capsular polysaccharide three-fold (from
      9.0 to 3.4% packed cell volume, P < 0.01). A temperature shift from 25 to 37
      degrees C decreased phenoloxidase activity three-fold (from 60.6 to 23.7 units mg
      1, P < 0.01) but not capsular polysaccharide (8.5 to 6.7% packed cell volume, P
      not significant). Thus, cryptococcal virulence factors are not regulated
      coordinately. Moreover, although the phenoloxidase synthesizes an antioxidant,
      melanin, the enzyme is not induced by the oxidant, hydrogen peroxide, or by a
      combination of hydrogen peroxide and solubilized ferric ion. As cryptococcal
      melanin is cheaply made from exogenous catechols, perhaps C. neoformans does not
      need to regulate the phenoloxidase strongly but, rather, can afford to synthesize
      the phenoloxidase at a moderate rate whenever it finds its growth limited.

PMID- 8873891
TI  - Random amplified polymorphic DNA analysis of culture collection strains of
      Candida species.
AB  - Random amplified polymorphic DNA (RAPD) profiles, obtained when screening culture
      collection strains of Candida spp., showed several species to be highly
      heterogeneous. The RAPD-defined groups were as follows: C. catenulata, two groups
      among five strains; Debaryomyces hansenii (anamorph C. famata), three groups
      among five strains; C. sake, three groups among three strains; C. intermedia, two
      groups among two strains; C. rugosa, two groups among three strains and C.
      parapsilosis, three groups among four strains. The five strains of Issatchenkia
      orientalis (anamorph C. krusei) belonged to a single RAPD-defined group. The two
      strains of the teleomorphic yeast Arxiozyma telluris had distinct RAPD profiles
      but neither resembled profiles of its anamorph, C. pintolopesii. The two
      varieties of C. pintolopesii had different RAPD profiles. Researchers are
      cautioned that organisms with the same name may not be closely related.

PMID- 8873892
TI  - Early diagnosis of Nelson's syndrome.
AB  - Nelson's syndrome is a specific form of Cushing's disease treated by bilateral
      adrenalectomy, presenting with a deep hyperpigmentation caused by a pituitary
      adenoma (corticotropinoma). These ACTH-secreting tumors are frequently
      aggressive, so early diagnosis is of prime importance. We have studied 33
      patients with Nelson's syndrome, 28 women and 5 men, aged 14-56 yr at the time of
      adrenalectomy and 16-58 yr at the time of Nelson's syndrome diagnosis (observed
      for 5-32 yr). Methods of examination included simultaneous adrenocorticotropic
      hormone (ACTH) and cortisol measurements during routine hydrocortisone
      replacement therapy, computed tomography (CT), pituitary magnetic resonance
      imaging (MRI), and visual field examination. The results obtained in a group of
      six patients diagnosed in the last 3 yr were compared with those obtained in a
      group of 27 patients examined before 1992. High plasma ACTH levels accompanied by
      normal serum cortisol concentration were characteristic for a late stage of the
      disease. Absolute temporal scotomas were an early finding. MRI, especially with
      the gadolinium enhancement, was superior to CT in demonstrating pituitary
      microadenomas in Nelson's syndrome. Thus, MRI diagnosis allowed for an early
      neurosurgical treatment of the patients with Nelson's tumors.

PMID- 8873893
TI  - Abnormal melatonin secretion in male patients with hypogonadism.
AB  - Recently we have demonstrated that melatonin secretion is increased in untreated
      male patients with GnRH deficiency. Testosterone administration to these patients
      decreased melatonin secretion to normal levels. These data, however, did not
      exclude a gonadotropic effect on melatonin secretion. To further elucidate
      whether gonadal steroids and/or gonadotropins modulate melatonin secretion in
      humans we compared untreated young males with hypogonadotropic hypogonadism (IGD,
      n = 6), and hypergonadotropic hypogonadism caused by KlinEfelter's syndrome (KS,
      n = 11) to normal pubertal male controls (n = 7). KS patients were subdivided
      into two groups: KS-1, with low testosterone; and KS-2, with normal testosterone
      levels. Serum samples for melatonin concentrations were obtained every 15 min
      from 7 PM to 7 AM in a controlled light-dark environment with simultaneous sleep
      recordings. All KS patients had elevated gonadotropin levels and decreased
      melatonin levels. Mean (+/- SD) dark-time nocturnal melatonin levels in KS-1 were
      92 +/- 21 pmol/L and were 146 +/- 46 pmol/L in KS-2 compared with 178 +/- 64
      pmol/L in controls. Integrated nocturnal melatonin secretion values (AUC) were 64
      +/- 14 pmol/min x L x 10(3) in KS-1 and 96 +/- 29 pmol/min x L x 10(3) in KS-2
      compared with 116 +/- 42 pmol/min x L x 10(3) in controls. All IGD patients had
      low gonadotropin and testosterone levels. Their dark-time melatonin levels (286
      +/- 26 pmol/L) and the AUC values (184 +/- 15 pmol/min/L x 10(3)) were increased.
      These data indicate that melatonin secretion is increased in male patients with
      GnRH deficiency and decreased in low testosterone hypergonadotropic hypogonadal
      patients. Taken together, our results suggest that both gonadotropins and gonadal
      steroids modulate melatonin secretion in humans.

PMID- 8873894
TI  - Regulation of VIP gene expression in general. Human lung cancer cells in
      particular.
AB  - Vasoactive intestinal peptide (VIP) is a neuropeptide of multiple functions
      affecting development and aging. In cancer, for example, VIP was found to
      function as an autocrine growth factor in nonsmall cell lung cancer (NSCLC)
      promotion. Furthermore, a VIP hybrid antagonist (neurotensin(6-11)-VIP(7-28)) was
      found to inhibit NSCLC growth. In the present study, the expression of VIP mRNA
      was studied using human lung cancer cells. RNA prepared from 19 cell lines was
      fractionated by 1% agarose gel electrophoresis followed by blotting onto
      nitrocellulose membranes and hybridization to a VIP-specific RNA probe. VIP mRNA
      was detected in about 50% of the cell lines tested with a greater abundance in
      NSCLC. Cultures of the NSCLC NCI-H727 cell line were treated with forskolin, an
      activator of cyclic AMP (cAMP), and separately with the tumor promoter phorbol 12
      myristate 13-acetate (PMA). Northern blot hybridization analysis showed an
      increase in VIP mRNA levels after 4 h treatment with 50 microM forskolin.
      Incubation with PMA also showed a significant increase in the levels of VIP
      transcripts. Cultures were then incubated with PMA in the presence of actinomycin
      D, a transcription blocker. Results indicated that PMA treatment may induce both
      VIP mRNA synthesis as well as VIP mRNA stabilization, and suggested a 4-5 h half
      life for the VIP mRNA in the absence of PMA. Thus, lung cancer tumor
      proliferation may be regulated, in part, at the level of VIP gene expression.

PMID- 8873895
TI  - Regulation of insulin-like growth factor I receptor gene expression by the Wilms'
      tumor suppressor WT1.
AB  - THe insulin-like growth factor I receptor (IGF-I-R) has been implicated in the
      etiology and/or progression of Wilms' tumor, or nephroblastoma, a pediatric
      neoplasm of the kidney that is often associated with deletion or mutation of the
      WT1 tumor suppressor gene. The levels of IGF-I-R mRNA in the tumors were sixfold
      higher than in normal adjacent kidney tissue and were inversely correlated to the
      levels of WT1 mRNA, suggesting that the expression of the IGF-I-R gene is under
      inhibitory control by WT1. Cotransfection of an IGF-I-R promoter-luciferase
      reporter construct together with a WT1 expression vector resulted in a dose
      dependent suppression of promoter activity. Multiple WT1 binding sites were
      mapped in the 5'-flanking and 5'-untranslated regions of the IGF-I-R gene using
      gel retardation and DNaseI footprinting assays. Thus, suppression of the IGF-I-R
      promoter by WT1 involves multiple interactions of its zinc finger domain with
      sites located both upstream and downstream of the transcription initiation site.
      Finally, we showed that expression of the endogenous IGF-I-R gene is decreased in
      G401 cells stably transfected with a WT1 expression vector. Reduction in
      expression of the IGF-I-R gene is associated with a decrease in a number of IGF-I
      mediated biological effects. Thus, deletion or mutation of the WT1 gene in Wilms'
      tumor and other malignancies can result in overexpression of the receptor, with
      enhanced autocrine/paracrine activation by locally produced or circulating IGFs.

PMID- 8873896
TI  - Regulation of stress-induced transcriptional changes in the hypothalamic
      neurosecretory neurons.
AB  - Transcriptional changes in corticotropin-releasing factor (CRF) and arginine
      vasopressin (AVP) gene expression were studied by in situ hybridization
      histochemistry using cRNA probes directed against intronic sequences. Acute ether
      stress resulted in a rapid induction of CRF and a delayed activation of
      vasopressin heteronuclear (hn)RNA in the parvocellular neurosecretory neurons
      within the paraventricular nucleus (PVN) of the hypothalamus. To explore possible
      molecular mechanisms regulating stress-related neuropeptide expression in vivo,
      the time-courses of stress-induced activation of different transcription factor
      classes were compared to that of changes in neuropeptide transcription. The peak
      of CRF transcription was parallel to that of cAMP response-element binding
      protein (CREB) phosphorylation but preceded the induction of c-fos and NGFI-B
      mRNAs and Fos protein. In contrast, AVP expression occurred in step with
      immediate-early gene (IEG) responses, suggesting involvement of different
      mechanisms underlying stress-induced neuropeptide responses. The interference of
      glucocorticoid hormones with stress-induced neuropeptide and transcription-factor
      responses has also been revealed in rats acutely or chronically pretreated with
      glucocorticoids. Acute dexamethasone injection did not prevent neuropeptide and
      transcription factor responses to either inhalation, whereas chronic
      corticosterone administration completely blocked IEG and neuropeptide induction
      in the stress-related neurosecretory neurons.

PMID- 8873897
TI  - Molecular dissection of corticosteroid action in the rat hippocampus. Application
      of the differential display techniques.
AB  - Both adrenal steroids and glutamate are crucial for hippocampal cell viability.
      In order to identify adrenal steroid- and glutamate-responsive genes controlling
      hippocampal cell viability, we have used the PCR-based differential display
      method. We have described the characteristics of this technique and how it can be
      automated. Using differential display, we have identified a number of rat
      hippocampal genes of which the expression is affected by a combination of the
      glutamate analog kainic acid and adrenalectomy. Administration of kainic acid or
      removal of the adrenals alone gave a limited number of differentially displayed
      genes. Therefore, our results indicate that the main mode of corticosteroid
      receptor-controlled gene expression in the hippocampus is interaction with other
      transcription factors (e.g., CREB, AP-1) and not by binding to hormone-responsive
      elements of corticosterone-specific genes. Characterization by multiplex PCR
      experiments of a differentially displayed fragment of which the expression is
      increased by the combination of kainic acid and adrenalectomy confirmed our
      differential display results. Further characterization by DNA sequence analysis
      of the corresponding full-length cDNA clone revealed a gene product with 91.4%
      sequence identity with the mouse transcription factor KROX-20, suggesting that we
      have cloned the rat homolog. This finding suggests a role of KROX-20 in
      corticosteroid- and kainic acid-controlled hippocampal plasticity.

PMID- 8873930
TI  - Near-fatal asthma in South Australia: descriptive features and medication use.

PMID- 8873898
TI  - The molecular genetics of schizophrenia.
AB  - There is overwhelming evidence for a significant genetic contribution to the
      etiology of schizophrenia. Molecular genetic techniques are now sufficiently
      advanced to be applied to complex genetic disorders with uncertain phenotypes,
      such as schizophrenia. In this article we first briefly discuss certain pertinent
      background issues: the evidence that schizophrenia has a heritable basis, the
      possible modes of inheritance involved, and how best to define schizophrenia in
      the light of this evidence; we then review the current status of research in the
      field. Large collaborative studies are currently underway that pave the way for
      the detection of genes of both major and minor effects. We may now be seeing the
      first consistently replicated results from chromosome 6 and 22 and from candidate
      genes, such as the dopamine D3 receptor gene.

PMID- 8873931
TI  - Evidence-based assessment of the benefit of revascularisation in coronary
      disease: beyond the randomised trials.

PMID- 8873932
TI  - What dose of vitamin E is required to reduce susceptibility of LDL to oxidation?
AB  - BACKGROUND: Oxidation modification of low density lipoprotein (LDL) may play a
      role in the pathogenesis of atherosclerosis. Ingestion of vitamin E in high
      dosage has been shown to reduce the susceptibility of LDL to copper-induced
      oxidation, as assessed ex vivo. AIM: To determine a minimum dose of supplementary
      vitamin E which will significantly reduce the susceptibility of LDL to oxidation.
      METHODS: A single centre, double-blind, parallel placebo-controlled trial.
      Healthy volunteers (total n = 42) were randomised to receive placebo, 500, 1000
      or 1500 IU/day of vitamin E (D-alpha-tocopherol) for a period of six weeks.
      Primary outcomes were change in lag time or oxidation rate to copper-induced LDL
      oxidation. Secondary outcomes were changes in plasma vitamin E levels and
      clinical tolerance. RESULTS: Lag time to LDL oxidation was significantly
      prolonged and oxidation rate significantly slowed at all dose levels of vitamin
      E, indicating a threshold effect from 500 IU/day. Compared to placebo, the median
      prolongation in lag time on 500 IU/day was 26%, on 1000 IU/day 24% and on 1500
      IU/day 35%. The corresponding slowing in oxidation rates was 14%, 19% and 25%
      respectively. The per cent change in plasma vitamin E concentration was highly
      correlated with the change in lag time (r = 0.61, p < 0.001) and oxidation rate
      (r = 0.55, p < 0.001). Vitamin E was generally well tolerated. CONCLUSIONS:
      Vitamin E in a dose of 500 IU/day will significantly reduce the susceptibility of
      LDL to oxidation. Whether or not this treatment will consistently reduce the
      future incidence of coronary artery disease will only be answered by further
      clinical trials.

PMID- 8873933
TI  - Patients' perceptions of food-induced asthma.
AB  - BACKGROUND: The influence of diet in asthma control remains unclear. However,
      there is likely to be a wide gap between patient perceptions and the probable
      actual role. Some 20-60% of people with asthma report food as a trigger factor
      while approximately 2.5% react to double-blind placebo-controlled challenges. The
      aim of this study was to determine: the frequency, type and sources of dietary
      advice being offered to patients, the prevalence of dietary modification, whether
      dietary changes were perceived to be of benefit and the type and sources of
      food/beverage reactions that people perceive they have experienced. METHOD: A
      self-administered 'food and asthma' questionnaire was developed and mailed to 156
      consecutive Alfred Hospital Asthma and Allergy Clinic patients registered on a
      computer database. RESULTS: The completed questionnaire response rate was 86.5%.
      Dietary advice had been offered to 47% of respondents while 61% had tried to
      modify their diet. Dietary restriction was the most common dietary modification.
      Where dietary restriction had occurred 79% of respondents perceived that this had
      improved their asthma control. A doctor was the most common source of dietary
      advice. Seventy-three per cent reported that food induced asthma. CONCLUSION: We
      confirmed that patients with asthma perceived diet to be important in their
      asthma control and that dietary modification is common despite its lack of
      objective basis. The influence of diet and asthma requires more research,
      evaluation and clinical attention.

PMID- 8873934
TI  - Sidestream smoke inhalation decreases respiratory clearance of 99mTc-DTPA
      acutely.
AB  - BACKGROUND: The permeability of the alveolar-capillary barrier to an inhaled
      aerosol of technetium 99m labelled diethylenetriamine penta-acetate (99mTc-DTPA)
      is used as an index of alveolar epithelial injury. Permeability is greatly
      increased in active smokers. AIMS: To determine the effect of sidestream smoke
      inhalation on permeability as this has not been described previously. METHODS: We
      measured lung clearance of inhaled 99mTc-DTPA aerosol in 20 normal non-smoking
      subjects before and after exposure to one hour's sidestream smoke inhalation.
      RESULTS: Measured carbon monoxide (CO) levels rose to maximum of 23.5 +/- 6.2 ppm
      (mean +/- SD) from baseline values of 0.6 +/- 1.3 (p < 0.001) and plasma cotinine
      levels to a maximum of 9.5 +/- 4.5 nmol/L (mean +/- SD). The half time (T1/2 in
      minutes) for 99mTc-DTPA clearance rose from baseline 69.1 +/- 15.6 (mean +/- SD)
      to 77.4 +/- 17.8 (p < 0.05) after smoke exposure. No effect of 99mTc-DTPA
      scanning or of sidestream smoke was demonstrated on lung function. CONCLUSIONS:
      We conclude that low level sidestream smoke inhalation decreases 99mTc-DTPA
      clearance acutely in humans. The mechanism of this unexpected result is not
      established but may include differences in constituents between sidestream and
      mainstream smoke, alterations in pulmonary microvascular blood flow, or changes
      in surfactant due to an acute phase irritant response.

PMID- 8873935
TI  - Microalbuminuria in type 2 diabetes: an independent predictor of cardiovascular
      mortality.
AB  - BACKGROUND: Microalbuminuria has been shown to be associated with cardiovascular
      mortality in type 2 diabetic subjects. It is unclear to what extent this is due
      to the increased prevalence of other cardiac risk factors. AIMS: To examine the
      relationship of urine albumin excretion to cardiovascular mortality and to
      determine its status as an independent risk factor. METHODS: In a prospective
      longitudinal study from 1986-1993 we followed 666 type 2 diabetic subjects from a
      diabetes outpatient service. Cardiovascular risk factors including urine albumin
      concentration were measured at study entry. Cox proportional hazards regression
      was used to determine risk factors for mortality. The hazard ratios of
      microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary
      heart disease mortality were determined after accounting for other cardiac risk
      factors including blood pressure, glycated haemoglobin, total cholesterol, HDL
      cholesterol, triglycerides, urea, smoking, body mass index, patient age and
      disease duration. RESULTS: The prevalence of urine albumin of 30-300 mg/L at
      study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular
      disease). Mortality hazard ratios in subjects with urine albumin of 30-300 mg/L
      as compared to < 30 mg/L, adjusted for age, sex and other cardiovascular risk
      factors were 1.77 (95% CI 1.22-2.57, p = 0.002) for all causes, 2.34 (95% CI 1.38
      3.99, p = 0.002) for cardiovascular and 1.78 (95% CI 0.97-3.26, p = 0.061) for
      coronary heart disease (CHD) mortality. Other factors significantly associated
      with cardiovascular mortality included diastolic blood pressure, HDL cholesterol
      and glycated haemoglobin. Total cholesterol and log triglyceride were
      significantly associated with CHD mortality. Disease duration, age at diagnosis,
      smoking and body mass index were not related to cardiovascular or CHD mortality.
      CONCLUSIONS: We confirm microalbuminuria as an independent predictor of mortality
      in type 2 diabetes despite its association with a number of conventional
      cardiovascular risk factors.

PMID- 8873936
TI  - Meningococcal disease in urban south western Sydney, 1990-1994.
AB  - BACKGROUND: There has been a sustained increase in incidence of meningococcal
      disease throughout Australia since 1987. In south western Sydney the incidence is
      higher than the national rate and a cluster of cases occurred in 1991 resulting
      in a widespread vaccination programme. AIMS: To investigate the clinical
      demographics of patients with meningococcal disease treated in south western
      Sydney, and to differentiate meningococcal strains to understand better the
      epidemiology in this urban setting. In addition, to investigate whether delays in
      diagnosis of meningococcal disease and institution of appropriate treatment were
      occurring. METHODS: Retrospective classification of notified cases as meningitis,
      septicaemia, meningitis/septicaemia, and other syndromes. Clinical information
      recorded to establish patterns of disease, delays in diagnosis and appropriate
      treatment, and outcome. Microbiological classification of organisms isolated by
      serogroup, serotype and subtype. RESULTS: Meningococcal disease primarily affects
      young children in winter months in south western Sydney, with a secondary peak of
      incidence in the 15-20 year old age group. 20.7% presented with meningitis only,
      22.4% with septicaemia only, and 53.4% with meningitis/septicaemia. There was a
      delay in diagnosis and institution of appropriate treatment of more than two
      hours in 21/58 (36.2%) patients including three of the six who died. No patient
      had received a parenteral antibiotic prior to coming to hospital -18.9% had
      received an oral antibiotic. The use of antibiotics before diagnostic lumbar
      puncture decreased the number of positive CSF cultures. However, in all but one
      patient with negative cultures there was other microbiological evidence of
      meningococcal disease. The mortality rate was highest (30.8%) in patients with
      septicaemia only, 6.5% in patients with meningitis/septicaemia and 0% in patients
      with meningitis only. Serogroup C was the predominant organism in all age groups.
      The predominant serotype was 2b (80% of serogroup C isolates). Subtypes were more
      variable but P1.2 occurred in 66.7% of serogroup C strains. CONCLUSIONS: There is
      a need for more education in our Health Area to improve the time taken to
      diagnose and institute appropriate treatment. The predominance of serogroup C is
      unusual in urban Australia where national data show serogroup B organisms
      predominate. Meningococci of phenotype C:2b:P1.2 have continued to cause disease
      in our Health Area for the past five years. This phenotype is uncommon in other
      areas of Australia.

PMID- 8873938
TI  - The use of thrombolytic therapy in patients presenting to a peripheral
      metropolitan emergency department with acute myocardial infarction.
AB  - BACKGROUND: While use of thrombolytic therapy in the management of acute
      myocardial infarction has become accepted practice in major teaching hospitals,
      its use in peripheral metropolitan hospitals has not been well accepted. AIM: To
      evaluate the use of thrombolytic therapy in the management of acute myocardial
      infarction in the Emergency Department (ED) of a peripheral metropolitan
      hospital. METHODS: A mixed prospective and retrospective observational study of
      69 patients with acute myocardial infarction, who received thrombolytic therapy
      during a three year period, was conducted in a community based ED. RESULTS:
      Demographic data, door to drug interval, complications occurring during
      administration of thrombolytics and subsequent interhospital transfer were
      recorded. The mean door to drug interval in 1992 was 79.7 minutes (95% CI: 50.7
      to 109.1) and by 1994 this had fallen to 25.6 minutes (95% CI: 18.9 to 32.3).
      Hypertension (22%) was the most common complication of therapy observed and
      cardiac arrest occurred in two cases (3.2%). A single episode of hypotension and
      vomiting were the only complications that occurred during interhospital transfer.
      There were no deaths during therapy or transfer. CONCLUSION: Thrombolytic therapy
      can be undertaken in the EDs of peripheral metropolitan hospitals in a safe and
      timely manner. There is little justification for routine medical escorts in the
      clinically stable post thrombolysis patient.

PMID- 8873937
TI  - Primary hyperaldosteronism: a missed diagnosis in 'essential hypertensives'?
AB  - BACKGROUND: It has been recognised recently that primary hyperaldosteronism may
      be more common than previously thought, the frequency of diagnosis being improved
      by screening using a plasma aldosterone concentration to renin activity ratio.
      AIMS: To determine the frequency of primary hyperaldosteronism, screening with
      both plasma aldosterone to renin concentration (PRC) and activity (PRA) ratios,
      in normokalaemic subjects previously diagnosed as having essential hypertension.
      METHODS: Plasma potassium, aldosterone and PRCs and PRA and blood pressure (BP)
      were measured in 74 hypertensive subjects previously diagnosed by one physician
      as having essential hypertension. A normal range for plasma aldosterone/renin
      ratios was determined in 147 control subjects. Hypertensive subjects with
      elevated aldosterone/renin ratios were further assessed for primary
      hyperaldosteronism using saline loading and fludrocortisone suppression. Those in
      whom plasma aldosterone concentration exceeded 140 pmol/L after suppression tests
      underwent adrenal vein sampling for measurement of aldosterone and cortisol
      concentrations as well as adrenal CT scanning to diagnose the cause of primary
      hyperaldosteronism. The main outcome measures were a diagnosis of aldosterone
      producing adenoma or bilateral adrenal hyperplasia based upon adrenal vein
      sampling. RESULTS: Four subjects (5%) had an elevated plasma aldosterone to renin
      ratio using PRC and six (8%) using PRA. Two subjects (2.7%) in this selected
      population had primary hyperaldosteronism, both of whom had BP > 160/110 mmHg at
      the time of testing. CONCLUSIONS: The frequency of normokalaemic primary
      hyperaldosteronism appears to be greater than previously thought, though the true
      incidence in the general population of hypertensive subjects remains unknown. The
      sensitivity of diagnosis (but not specificity) may be improved by measurement of
      the plasma aldosterone/renin ratio and PRC is at least as adequate as PRA for
      this process.

PMID- 8873939
TI  - Advances in the understanding of neuroendocrine function in rheumatic disease.

PMID- 8873940
TI  - Death and medicine.

PMID- 8873941
TI  - Hyperglycaemia on the surgical wards: a three year follow up study.

PMID- 8873943
TI  - A case of factitious breast cancer in order to receive chemotherapy.

PMID- 8873942
TI  - Balloon pericardiostomy: a new therapeutic option for malignant pericardial
      effusion.

PMID- 8873944
TI  - Acute necrotising myopathy in a critically ill patient.

PMID- 8873945
TI  - Tuberculous lymphadenitis: revisiting an old foe.

PMID- 8873946
TI  - Lung function test findings in patients with chronic fatigue syndrome (CFS)

PMID- 8873947
TI  - Left atrial appendage thrombus in atrial fibrillation post coronary artery bypass
      grafting (CABG)

PMID- 8873948
TI  - Melioidosis causing encephalomyelitis.

PMID- 8873949
TI  - Cogan's syndrome.

PMID- 8873950
TI  - Allogeneic bone marrow transplantation for relapsed acute myeloid leukaemia (AML)

PMID- 8873951
TI  - Smoking cessation programmes are neglecting the needs of persons with
      neuropsychiatric disorders.

PMID- 8873952
TI  - Mucoid impaction presenting as multiple pulmonary nodules in cystic fibrosis.

PMID- 8873953
TI  - Racial differences in incidence, outcome, and quality of life for African
      Americans on hemodialysis.
AB  - African-Americans are the fastest growing racial minority with end-stage renal
      disease (ESRD) in the United States. Although comprising < 15% of the US
      population, African-Americans comprise approximately 31% of the ESRD population.
      African-Americans are approximately 7 years younger than their white counterparts
      with ESRD. Surprisingly, although African-Americans systematically receive less
      dialysis than whites, their survival with ESRD is greatly improved. This improved
      survival with ESRD is accompanied by an improved quality of life for African
      Americans. In this review, we will examine the reasons why African-Americans have
      an excessive incidence of selective diseases that culminate in ESRD. Furthermore,
      we will judge several hypotheses that may account for the improved survival
      enjoyed by African-Americans with ESRD. We contend that research targeted to
      clarify the basis for these differences between African-Americans and whites with
      ESRD will improve the outcomes for both populations.

PMID- 8873954
TI  - Diabetic nephropathy and end-stage renal disease in Mexican Americans.
AB  - Hispanics are the second largest minority group in the United States. Mexican
      Americans (MAs) are the largest subgroup at 14 million in 1990. MAs have a two-
      to threefold increased prevalence of non-insulin-dependent diabetes mellitus.
      Population-based studies of MAs with non-insulin-dependent diabetes have shown
      that these patients may be more likely than non-Hispanic whites to develop
      proteinuria and are more likely to develop end-stage renal disease. The reasons
      for this excess risk are yet to be completely elucidated, but may be due to worse
      glycemic control, worse blood pressure control when hypertension does occur,
      worse access to medical care, and/or genetics. When MAs are treated for diabetic
      end-stage renal disease, they have better survival. Much less data are available
      for other Hispanic subgroups. From a public health perspective, higher incidence
      and longer survival as well as relatively young and rapidly growing population
      predict an increasing burden for MAs if prevention measures are not instituted
      soon.

PMID- 8873955
TI  - Access of Native Americans to renal transplantation in Arizona and New Mexico.
AB  - Lower rates of transplantation among minority groups are a nationally recognized
      phenomenon. Native Americans (NA) nationally have nearly four times the risk of
      end-stage renal disease (ESRD) as compared with white (W) Americans and are
      significantly overrepresented in the Network 15 ESRD population. To understand
      more about NA and W transplant rates, we looked at all reported Arizona (AZ) and
      New Mexico (NM) resident cases from the Network No. 15 data base. Age of onset,
      sex, primary diagnosis, payment source, transplant donor source, and other
      factors were examined. NA experienced a slightly earlier onset of ESRD than W,
      and diabetes mellitus was the primary ESRD diagnosis for 63-73% of NA and for 34
      39% of W. Because age distribution and frequency of diabetes mellitus of the NA
      ESRD population differ from those of W in the Network, age-specific and diagnosis
      specific transplant rates were examined. Age-adjusted transplant rates per 100
      ESRD patients for AZ were 16.4 (NA) and 21.0 (W) and for NM 14.2 (NA) and 22.4
      (W). Diagnosis-specific age-adjusted transplant rates for patients with the
      primary diagnoses of diabetes mellitus and glomerulonephritis, the two most
      common causes of ESRD among NA, showed a large difference between W and NA rates.
      Age-adjusted rates for diabetes were: AZ 8.4% (NA) and 14.5% (W); NM 9.8% (NA)
      and 15.9% (W). Age-adjusted rates for patients with glomerulonephritis were: AZ
      23.7% (NA) and 28.0% (W); NM 22.3% (NA) and 33.0% (W). In all comparisons and in
      both the W and NA ESRD populations, women were transplanted at lower rates than
      men. NA experienced a greater delay from onset of treated ESRD to transplant than
      W. Payment source and transplant donor source did not appear to be significantly
      different between NA and W. The lower transplant rates in NA versus W in Network
      No. 15 cannot be explained by age- or diagnosis-specific factors.

PMID- 8873956
TI  - Atherosclerotic renovascular disease as a cause of end-stage renal disease: cost
      considerations.
AB  - Atherosclerotic vascular disease affects an increasing number of patients with
      end-stage renal disease. A review of comorbid atherosclerotic disease in 7,200
      end-stage renal disease patients indicated that occlusive disease of the renal
      arteries may contribute to progressive renal failure in 1.34% of the US dialysis
      population or in 14% of the Caucasian patients with hypertensive nephrosclerosis.
      The costs of dialytic care in such patients exceed USD 87 million annually. The
      risks and costs of surgical revascularization of such patients are large,
      however. These data argue that prospective trials of intervention in
      atherosclerotic renal artery disease are urgently needed.

PMID- 8873957
TI  - Treatment of hypertension in renal failure patients: when do we overtreat? When
      do we undertreat?
AB  - Despite the commonplace nature of hypertension in chronic dialysis patients, many
      issues remain unresolved. According to current JNC/V (see text) recommendation, a
      systolic blood pressure of < 120 mm Hg is optimal, 120-129 mm Hg is normal, and
      one of 130-139 mm Hg is high-normal. The majority of dialysis patients receiving
      treatment in the United States is probably not maintained in the optimal blood
      pressure range. However, if the J curve hypothesis has credence, many of our
      dialysis patients may be susceptible to overtreatment, especially of their
      diastolic blood pressure. In patients with ischemic cardiovascular disease,
      several studies show a decrease in survival with diastolic blood pressures < 85
      mm Hg. This J curve phenomenon is seen predominantly in patients with ischemic
      heart disease. Since many, and possibly most, of the currently treated end-stage
      renal disease patients in the United States have existing atherosclerotic
      cardiovascular disease when they start chronic dialysis therapy, lowering of the
      diastolic blood pressure below a J threshold may be dangerous. This problem may
      be especially prevalent in diabetics with diabetic cardiomyopathy. Diabetics and
      other end-stage renal disease patients may be started on hemodialysis with
      glomerular filtration rates in the 10- to 15-cm2/min range. Patients with high
      residual renal function may have small intradialytic weight gains and frequent
      intradialytic hypotension. This 'overtreatment' may lead to postdialysis
      arrhythmias and sudden death in chronic dialysis patients. As in the nonrenal
      failure population, end-stage renal disease patients with left ventricular
      hypertrophy have a 2- to 3-fold increased risk of death from cardiovascular
      diseases, and all cause mortality. In contrast to nonrenal failure patients,
      normotensive ESRD patients may show an increase of left ventricular mass over
      time. Although left ventricular hypertrophy can be reversed with good blood
      pressure control, patients are often undertreated based on analysis of dialysis
      clinic blood pressures. Even if clinic systolic blood pressure levels are
      optimal, chronic dialysis patients may still have unacceptably high ambulatory
      blood pressure levels due to a rise in nocturnal blood pressure with sleep.

PMID- 8873958
TI  - Ischemic heart disease in chronic uremia.
AB  - The burden of ischemic heart disease is high in dialysis patients. Ischemia may
      result from atherosclerotic and nonatherosclerotic disease and may cause
      myocardial infarction and angina. The impact of diminished perfusion is
      intricately associated with the underlying cardiomyopathy, both of which
      predispose to heart failure. The etiology of ischemia is complex and associated
      with the underlying cardiomyopathy, whether it be concentric left ventricular
      hypertrophy, left ventricular dilatation, or systolic dysfunction. Hypertension,
      diabetes, dyslipidemia, abnormalities of divalent ion metabolism,
      hypoalbuminemia, and left ventricular hypertrophy are probably adverse risk
      factors for ischemia, but the relative importance of each is unknown.

PMID- 8873959
TI  - Factors affecting renal allograft survival in African Americans.
AB  - African Americans are more likely to develop end-stage renal disease than other
      racial groups. Although transplantation is optimal therapy for most end-stage
      renal disease patients, many potential black recipients do not have ready access
      to cadaveric kidneys. Following transplantation, blacks are at increased risk of
      allograft loss as a result of the interaction of multiple immunologic and
      nonimmunologic factors.

PMID- 8873960
TI  - Paget's disease and osteoclast biology.
AB  - Paget's disease is the most exaggerated example of bone remodeling in which
      abnormal osteoclastic bone resorption remains coupled to new bone formation.
      There are abnormalities in the stages of osteoclast development, and studies in
      Paget's disease have suggested a major role for IL-6 in human osteoclast
      activity. The pathophysiologic basis for these abnormalities is not clearly
      defined, except that the primary cellular abnormality resides in the osteoclast.
      Many important questions about the pathophysiology of Paget's disease still
      remain to be answered, including: (1) What is the identity of the virus in
      pagetic osteoclasts?; (2) Are Paget's patients in different geographical locales
      harboring a similar virus in their osteoclasts, or can different paramyxoviruses
      induce Paget's disease?; (3) How is the virus maintained and propagated for many
      years, so that it can be expressed in the osteoclast, a cell with a finite
      lifespan?; and (4) Since Paget's disease has a very high familial tendency, with
      up to 40% of patients having an affected relative, what is the genetic locus
      associated with Paget's disease, and does this genotype result in an increased
      propensity for hematopoietic cells such as the osteoclast to harbor
      paramyxoviruses? The application of the techniques of molecular and cell biology
      to Paget's disease should provide answers to some of these questions and give
      important insights into the normal bone remodeling process.

PMID- 8873961
TI  - 17 beta-estradiol increases calcium content in fetal mouse parietal bones
      cultured in serum-free medium only at physiological concentrations.
AB  - Using a bone organ culture system that shows mineralization in vitro, we
      investigated whether 17 beta-estradiol dose-dependently increases calcium content
      in cultured calvarial bones in serum-free medium. Fetal mouse parietal bones (3 x
      3 mm) were cultured in phenol red-free BGJ medium containing phosphate (3-4
      mmol/L), calcium (1-1.25 mmol/L), insulin (6 micrograms/ML), and transferrin (6
      micrograms/mL) for 4-5 days. Under these culture conditions, the calcium content
      of the cultured bones (at dissection 34.0 +/- 4.6 micrograms/bone [mean +/- SD],
      n = 50) increased by 15-20 micrograms during 4-5 days of culture. 17 beta
      Estradiol increased the calcium content significantly at 10(-12) to 10(-11)
      mol/L, but not at lower (10(113) mol/L) or higher (10(-10) to 10(-9) mol/L)
      concentrations. 17 alpha-Estradiol had no effect. The stimulatory effect of 17
      beta-estradiol was completely inhibited by the antiestrogen agent ICI-182,780.
      The anabolic effect of 17 beta-estradiol was elicited not only in bones from
      females but also in those from males. 17 beta-Estradiol had no significant effect
      on 45Ca release from prelabeled parietal bones. Furthermore, light- and electron
      microscopic examinations revealed that bone mineralization proceeded through
      formation of matrix vesicles, without any metastatic or dystrophic calcification.
      These in vitro findings suggest that 17 beta-estradiol elicits small, but
      reproducible, direct effects on calcium content in the parietal bones not only in
      female but also in male fetal mice at physiological-free E2 concentrations (10(
      12)-10(-11) mol/L), which is attainable in serum of normal human subjects. In
      contrast to in vivo studies, pharmacological doses of 17 beta-estradiol had no
      anabolic effect on parietal bones. The mechanism of such a biphasic effect of
      estrogens remains to be elucidated.

PMID- 8873962
TI  - Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse
      calvariae.
AB  - Reactive oxygen species such as superoxide and hydrogen peroxide have been
      implicated as regulatory factors in the control of osteoclastic bone resorption.
      While superoxide radicals have been suggested to be the main bone resorbing
      species in organ culture and in vivo, hydrogen peroxide (H2O2) has recently been
      shown to activate isolated osteoclasts in vitro. In this study, we investigated
      the effects of hydrogen peroxide and superoxide on bone resorption in mouse
      calvarial organ cultures. Hydrogen peroxide stimulated bone resorption in a
      concentration-dependent manner in calvarial organ cultures with a maximal effect
      at 1 mumol/L (45Ca release; treated/control = 1.6 +/- 0.07; p < 0.001 from
      control). Bone resorption induced by H2O2 was significantly inhibited by catalase
      to 1.2 +/- 0.05; p < 0.02. In contrast, the combination of xanthine and xanthine
      oxidase, which generates superoxide anions, failed to stimulate bone resorption,
      except in the presence of superoxide dismutase (SOD), which resulted in a modest
      increase in bone resorption to a treated/control ratio of 1.2 +/- 0.05; p < 0.02.
      Analysis of calvarial bones which were exposed to H2O2 showed a significant
      increase in osteoclast numbers suggesting that H2O2 may be capable of stimulating
      osteoclast formation in addition to enhancing activity of mature osteoclasts. Our
      data are consistent with previous work, which has shown that H2O2 is a bone
      resorbing factor with effects on both osteoclast formation and in activity of
      mature osteoclasts. The experiments with SOD further suggest that the enhancement
      of bone resorption previously noted with superoxide generating systems may be due
      in part to generation of H2O2.

PMID- 8873963
TI  - Effect of estrogen status on bone regulating hormones.
AB  - The effect of surgically induced menopause and a subsequent estrogen monotherapy
      on the secretion of calciotropic hormones and serum minerals was evaluated in 11
      perimenopausal menstruating women. In seven of them, plasma insulin growth factor
      I was also assessed. In the 12th-16th week after bilateral oophorectomy, a
      decline of serum PTH (p < 0.01) and an increase of calcemia (p < 0.05),
      phosphatemia (p < 0.05), and IGF-I (p < 0.01) were documented. A subsequent
      transdermal estrogen substitution (100 micrograms/day for 6 weeks) returned these
      values to the preoperative range. However, neither the operation nor the estrogen
      treatment altered calcitonin secretion (basal and calcium stimulated), serum
      1,25(OH)2, vitamin D3, or magnesium. The effectiveness of oophorectomy as well as
      compliance of estrogen substitution was documented by serum estradiol, FSH, and
      LH response. The results demonstrate a stimulating effect of estrogen on PTH
      secretion, secondary to an estrogen-induced reduction in plasma calcium. They
      further demonstrate an inhibitory effect on phosphatemia and IGF-I production,
      but no effect on calcitonin secretion and vitamin D metabolism.

PMID- 8873964
TI  - Three-year controlled, randomized trial of the effect of dose-specified loading
      and strengthening exercises on bone mineral density of spine and femur in
      nonathletic, physically active women.
AB  - The objectives of this study were to evaluate (1) the effect of spinal muscle
      strengthening by loading exercises on the bone mineral density (BMD) of the
      spine, and (2) the effect of upper extremity loading exercises on the BMD of the
      midradius and femur in healthy, premenopausal women. The study design was a
      randomized, controlled trial of 3 years' duration. Ninety-six healthy,
      premenopausal, white women aged 30-40 years participated; 67 completed the study.
      All subjects were in good health (normal menses) and were active, but not
      athletic (that is, not involved in a regular sport activity). Subjects were
      randomized to an exercise or control group. The exercise group performed a
      supervised, non-strenuous, weight-lifting exercise program. Exercise performance
      was supervised once a week at the medical facility. In addition, the subjects
      performed the exercises twice a week on their own. Dietary calcium intake was to
      be maintained at 1,500 mg/day in both groups. Bone density was measured at the
      lumbar spine and hip with dual-energy X-ray absorptiometry at 0, 1, and 3 years.
      BMD of the midradius was measured with single photon absorptiometry. Measurements
      of muscle strength were obtained at baseline and every 3 months for 3 years.
      Maximal oxygen uptake was measured, and the level of physical activity was
      recorded. Compliance with the exercise program was excellent during the first
      year of the study, but decreased thereafter. At the end of 3 years, subject
      withdrawal was about 34% from the exercise group and about 22% from the control
      group (total subject withdrawal was about 30%). Muscle strength in the exercise
      group increased significantly at all involved skeletal sites (p values all <
      0.001). There was a modest positive correlation between the BMD of Ward's
      triangle with spinal flexor strength (r = 0.32, p = 0.008) and with grip strength
      (r = 0.38, p = 0.001). Comparing study groups, we found no significant effect of
      the loading and nonstrenuous strengthening exercises in the exercise group or
      free physical activity group (our control group) on BMD at the spine, hip, or
      midradius measurement sites. In active, but not athletic premenopausal women,
      additional moderate weight-lifting exercises showed no significant effect on BMD.

PMID- 8873965
TI  - Ultrastructural localization of alpha-parvalbumin in the epiphyseal plate
      cartilage and bone of growing rats.
AB  - The distribution of the calcium-binding protein, alpha-parvalbumin, in the
      epiphyseal plate cartilage and bone of growing rats was examined by electron
      microscope immunocytochemistry of undecalcified samples. Parvalbumin
      immunoreactivity, as revealed by gold particles, increased with maturation of
      chondrocytes and was maximal in the zone of calcification. It was found in the
      cytoplasm of chondrocytes, osteoblasts and osteocytes, corroborating light
      microscope observations. The immunolabeling was associated with amorphous
      electron-dense material in the cytoplasm and not bound to membranes. There was
      moderate parvalbumin immunolabeling over the dense chromatin in the nuclei of
      chondrocytes and bone cells, but none in the cell processes of mature and
      hypertrophic chondrocytes, in the matrix vesicles themselves, or in the cell
      processes of osteoblasts. However, there was parvalbumin immunoreactivity in the
      cell processes of the osteocytes of compact cortical bone. The uncalcified and
      calcified matrix of the epiphyseal cartilage, the osteoid, and the fully
      mineralized cortical bone were devoid of parvalbumin immunoreactivity. Thus,
      immunoreactive parvalbumin is confined to the cell bodies of chondrocytes and
      osteoblasts, and is unlikely to be directly involved in mineral deposition. The
      maximal parvalbumin immunoreactivity in the last terminal chondrocytes of the
      zone of calcification suggests that the protein is involved in buffering
      intracellular Ca2+, preventing the stimulation of degenerative processes by high
      intracellular calcium. The parvalbumin immunoreactivity in the cell processes of
      osteocytes of compact cortical bone seems to indicate that this calcium-binding
      protein may be involved in the regulation of Ca2+ fluxes and hence in calcium
      homeostasis in bone.

PMID- 8873966
TI  - Hepatocyte growth factor and its actions in growth plate chondrocytes.
AB  - Hepatocyte growth factor (HGF) has been implicated as a paracrine regulator of
      organogenesis and repair in many tissues. Here we have studied the expression and
      actions of HGF in intact rachitic rat growth plate and derived cultures of
      proliferative zone chondrocytes. In vivo and in vitro chondrocytes express HGF
      mRNA; 1,25(OH)2 has a three-fold maximal stimulatory effect, which can be blocked
      by H-7, an inhibitor of protein kinase C. Although HGF elaboration and action
      generally follow a paracrine model, chondrocytes appear capable of both
      expressing and responding to HGF. mRNA encoding the HGF receptor (c-met) was
      detected in both growth cartilage and derived chondrocyte cultures. HGF addition
      to chondrocyte cultures increased collagen II mRNA and alkaline phosphatase
      enzymatic activity to degrees comparable to that observed for active vitamin D
      metabolites. Combining HGF and 1,25-D evoked a synergistic response (ninefold) of
      alkaline phosphatase activity. To assess whether a similar stimulatory effect
      might be seen with bioactive peptides and HGF, we investigated the effect of HGF
      pretreatment on acute responses of chondrocytes to synthetic human calcitonin, an
      anabolic chondrocyte regulator whose skeletal action are mediated principally by
      cAMP elevation and subsequent protein kinase A activation. CT's maximal
      activation of protein kinase A was increased by prior HGF treatment from 56% to
      78%. In concert, our findings indicate that in addition to HGF's classical
      paracrine role during skeletal growth, this growth factor may modulate hormonal
      sensitivity of the chondrocyte during proliferation, differentiation, and/or
      apoptosis.

PMID- 8873967
TI  - Ceramide-induced nuclear translocation of NF-kappa B is a potential mediator of
      the apoptotic response to TNF-alpha in murine clonal osteoblasts.
AB  - Osteoblasts are affected by TNF-alpha overproduction by immune cells during
      inflammation. We demonstrate that apoptosis is induced in murine osteoblastic
      MC3T3-E1 cells by exceeding the concentrations 100 units/mL of TNF-alpha and 10
      mumol/L of synthetic ceramide. The apoptotic signaling pathway activated by TNF
      alpha was examined in MC3T3-E1 cells. Endogenous cellular ceramide concentrations
      increased within 3 min, and comparable peak levels were observed for 30 min after
      TNF-alpha treatment. Activation of nuclear factor-kappa B (NF-kappa B) was
      detected after TNF-alpha or synthetic ceramide stimulation. The concentration of
      NF-kappa B increased in the perinuclear region after 5 min of treatment and
      translocation into the nucleus was observed within 15 min of treatment.
      Degradation of I kappa B alpha/MAD-3 was observed after 60 min of ceramide
      treatment. These results indicate that nuclear translocation and activation of NF
      kappa B through TNF-alpha generated ceramide may be one important apoptotic
      signaling pathway in MC3T3-E1 cells. The osteoblastic apoptosis triggered by TNF
      alpha-generated ceramide may explain the inhibition of bone formation during
      severe bone inflammation.

PMID- 8873968
TI  - Development and characterization of a porcine model to study osteoclast
      differentiation and activity.
AB  - The study of osteoclast differentiation, function, and fate has been hampered by
      the lack of nonavian, nonrodent models in which biochemical and molecular studies
      can be conducted. The present study was undertaken to determine if osteoclasts
      could be generated from porcine bone marrow cells. Bone marrow from the long
      bones of neonatal female pigs was enriched for mononuclear cells and cultured in
      the presence or absence of 1,25-(OH)2D3, rhIL-11, or PGE2. A confluent layer of
      stromal cells was observed after 4-8 days in culture and multinucleated giant
      cells formed after 6-10 days of culture. The multinucleated cells stained
      positively for tartrate-resident acid phosphatase and formed resorption lacunae
      when exposed to bovine cortical bone slices. When examined by transmission
      electron microscopy, abundant mitochondria, perinuclear Golgi complexes, numerous
      variably sized vacuoles, prominent rough endoplasmic reticulum, and free
      polysomes were observed in the multinucleated cells. Stimulation of the in vitro
      generated osteoclasts with 10(-8) mol/L salmon calcitonin resulted in a three to
      fivefold increase in cAMP production and in cell retraction. Although the
      osteoclasts formed in the presence or absence of 1,25-(OH)2D3, 10-50-fold more
      osteoclasts were observed in the cultures treated with 1,25-(OH)2D3 in comparison
      to cultures without 1,25-(OH)2D3. Osteoclast differentiation was also stimulated
      by rhIL-11 and PGE2; although, the number of cells generated in 6-7 days was
      significantly less than the number obtained with 1,25-(OH)2D3, treatment. In
      addition, these multinucleated cells expressed high levels of Src kinase activity
      and responded to bafilomycin A1, an inhibitor of the vacuolar type H(+)-ATPase,
      treatment with a decrease in osteoclastic bone resorption. In summary, the
      porcine cells possess the major distinguishing characteristics of osteoclasts and
      provide an alternative mammalian model to study osteoclast differentiation and
      resorptive activity.

PMID- 8873969
TI  - Comparison of the distribution of 3H-alendronate and 3H-etidronate in rat and
      mouse bones.
AB  - Alendronate and etidronate are bisphosphonates used clinically to treat diseases
      associated with increased bone resorption. Etidronate is less potent and was
      reported to cause osteomalacia. This study examines if differences in
      distribution of alendronate and etidronate in the skeleton can explain
      differences in efficacy and in effects on mineralization between the two drugs.
      Eight-day old rat pups were injected s.c. with 3H-alendronate or 3H-etidronate
      both at either 1.3 mumol/kg or at their respective pharmacological effective
      doses in the growing rat of 0.12 mumol/kg for alendronate and 72.8 mumol/kg for
      etidronate. Twelve hours after administration at 1.3 mumol/kg both drugs showed a
      three- to fourfold higher localization on osteoclast vs. osteoblast surface. At
      the pharmacologically effective doses, 3H-alendronate labeled eightfold more
      osteoclast surface than osteoblast surface. In contrast, 3H-etidronate labeled
      approximately equal fractions of osteoclast and osteoblast surface. When similar
      doses of 3H-etidronate and 3H-alendronate (0.24 mumol/kg 3H-etidronate vs. 0.20
      mumol/kg 3H-alendronate; 1.5 mumol/kg 3H-etidronate vs. 1.2 mumol/kg 3H
      alendronate; and 14.6 mumol/kg 3H-etidronate vs. 12.0 mumol/kg 3 H-alendronate)
      were injected intravenously into adult mice at similar specific activities, 3H
      etidronate labeled 1.5-2.5 times more osteoclast surface than 3-H-alendronate,
      but 3 to 15 times more osteoblast surface. Consequently, the ratio between the
      fraction of labeled osteoclast surface and the fraction of labeled osteoblast
      surface ranged for 3H-alendronate from 9 to 24, whereas for 3H-etidronate the
      range was from 4 to 7, due to more extensive labeling of osteoblast surface by 3H
      etidronate. In a third experiment, we confirmed in adult mice the previous
      observation made in rat pups that normal bone formation occurs over alendronate
      covered bone surfaces, and found that it occurred over etidronate-covered
      surfaces as well. Forty nine days after s.c. administration of alendronate at
      0.12 mumol/kg or etidronate at 1.3 mumol/kg or 55.3 mumol/kg into adult mice bone
      formed over drug label. The distance from incorporated label to bone surface for
      both drugs (12.7 microns for alendronate and 8.7 and 9.2 microns for etidronate)
      was similar to wall width (defined by cement line) in controls (10.6 microns). In
      conclusion, alendronate, especially at pharmacologically active doses, shows
      higher uptake on resorption vs. formation surfaces than etidronate. The extent of
      bone formation on surfaces containing alendronate or etidronate is similar and is
      comparable to the "wall width" in controls.

PMID- 8873970
TI  - High bone turnover is associated with low bone mass in both pre- and
      postmenopausal women.
AB  - In 979 healthy women, aged 30-75 years, bone mass was measured by DXA in the
      lumbar spine and proximal femur, and by SXA in the distal forearm. Bone turnover
      was assessed by urinary CrossLaps (CrossLaps ELISA), a new assay which measures
      type I collagen degradation products in urine and by osteocalcin (two-site N-Mid
      hOsteocalcin ELISA), a new assay which measures the N-terminal-mid fragment (1
      43) as well as the intact (1-49) osteocalcin (OCN-Mid) in serum. For comparison
      data on urinary hydroxyproline (fU Hpr/Cr) and serum, total alkaline phosphatase
      were included (AP). In premenopausal women below 50 years of age, the
      concentrations of the biochemical markers were stable with age. At menopause
      CrossLaps and OCN-Mid increased abruptly to a level 60% and 35% above the
      premenopausal mean values (p < 0.001). Premenopausal women in the highest
      quartiles, stratified according to the concentration of CrossLaps and OCN-Mid
      corrected for height and weight, had 6%-11% lower bone mass in all regions (p <
      0.01) as compared to women in the lowest quartiles. CrossLaps and OCN-Mid
      corrected for height and weight correlated with bone mass in the spine and
      proximal femur, r = -0.13 to r = -0.28, p < 0.05. In postmenopausal women, the
      difference in bone mass between the highest and lowest quartiles was 8%-14% (p <
      0.001). CrossLaps and OCN-Mid correlated with bone mass measured in all regions,
      r = -0.14 to r = -0.32, p < 0.05. The correlation between bone mass and AP and Fu
      Hpr/Cr was lower; r = -0.06 to r = -0.20 for premenopausal women, NS to p < 0.01,
      and r = -0.01 to r = -0.23, NS to p < 0.001 for postmenopausal women. In
      conclusion, the present data indicate that high bone turnover is associated with
      a significantly lower bone mass in not only postmenopausal, but interestingly
      also in premenopausal women. In consistence with previous results, we found that
      bone turnover increased perimenopausally and in the early menopause.

PMID- 8873971
TI  - Nitric oxide synthase 1 and nitric oxide synthase 3 protein expression is
      regionally and temporally regulated in fetal brain.
AB  - Two constitutively expressed isoforms of nitric oxide synthase (NOS) have been
      identified, Nos1 and Nos3. Nos1 was originally identified in neuronal cells and
      Nos3 in endothelial cells. Because the biochemical activity of NOS is
      developmentally regulated, we tested the hypothesis that protein expression is
      also developmentally regulated. Antibodies to Nos1 and Nos3 were evaluated for
      specificity by immunoblotting and then used for immunohistochemistry. In fetal
      and adult sheep brain homogenates, Nos1 antibodies identified one immunoreactive
      band of proteins at 155 kDa. The Nos3 antibody detected one immunoreactive band
      at 145 kDa that comigrated with a reactive band in endothelial cell lystates.
      Immunoblots of developing neocortex demonstrated that Nos1 was enriched at early
      gestational ages, whereas Nos3 expression was relatively constant throughout
      development. By immunohistochemistry, distinct isoform-specific patterns of
      immunoreactivity were detected. At 60 days, Nos1 immunoreactivity is primarily
      localized in neuropil, but by midgestation, nonpyramidal neurons are labeled in
      the cortical plate. Developing neurites are Nos1-positive at 60 and 71 days,
      decreasing in abundance by 93 days. By 93 days the striatum is fully populated by
      Nos1-expressing nonprincipal neurons. In hippocampus and subthalamic nucleus,
      Nos1 immunoreactivity is greatest at 60 and 71 days gestation, decreasing
      thereafter. Immunoreactivity for Nos3 delineates cerebrovasculature maturation
      from a primarily radial to a highly complex branching arrangement. Hindbrain
      structures achieve mature organization of the cerebrovasculature before
      forebrain. We conclude that constitutive NOS protein expression is
      developmentally regulated and that distinct isoforms of NOS are regulated
      differentially during brain development. Expression of Nos3 parallels maturation
      of the cerebrovasculature, whereas the transient, region- and cell type-dependent
      enrichment of Nos1 in the developing brain may indicate a temporally and
      spatially restricted role for this enzyme in the maturation of specific neuronal
      populations.

PMID- 8873972
TI  - Appearance of neurofilament subunit epitopes correlates with electrophysiological
      maturation in cortical embryonic neurons cocultured with mature astrocytes.
AB  - E14 rat cortical neurons which have almost no glial progenitors were cocultured
      with a homogeneous population of mature type 1 astrocytes at a 4/1 ratio in serum
      free medium. Maturation of neurons was evaluated using a set of well
      characterized antibodies and two new monoclonal antibodies (MN2E4 and MN3H6)
      raised against various neurofilament subunits and whole-cell patch clamp
      experiments. We observed that this coculture method leads to a well-timed and
      very homogeneous neuronal maturation and that sequential appearance of
      neurofilament subunits in developing neurons correlates with the
      electrophysiological maturation. This sequence, early expression of the 68 kDa
      neurofilament subunit and late appearance of the 200 kDa neurofilament subunit,
      occurs in normal brain development, which validates this culture model as a
      useful tool for studying neuronal maturation and differentiation. MN2E4 staining
      (non-phosphorylated 200 kDa cytoskeletal protein antibody) appeared just before
      the neurons became excitable. It could thus be used as a functional neuronal
      marker. MN3H6 staining (phosphorylated 160-200 kDa neurofilament subunit
      antibody) appeared just after the neurons made synaptic contacts and generated
      synaptically driven spike bursts. This finding indicated that some phosphorylated
      epitopes of 160-200 kDa neurofilament followed synaptogenesis. These processes
      may play a key role in stabilizing the synapses to achieve a functional neuronal
      network.

PMID- 8873973
TI  - Immunocytochemical analyses of astrocyte development in the olfactory bulb.
AB  - Several lines of evidence suggest an important role for glia in establishing
      boundaries during development of mammalian cortex and insect olfactory lobe. In
      the adult rat olfactory bulb distinct morphological categories of astroglial
      cells with clear laminar specificity are easily recognized following
      immunocytochemical staining of glial fibrillary acidic protein (GFAP). To explore
      the developmental distribution of olfactory bulb astrocytes and their possible
      role in establishing the segregation of neurons in specific olfactory bulb
      laminae, we used immunocytochemical localization of GFAP in rats at 0, 6, 9, 12,
      15 and 21 days postnatal plus the adult. In the adult we confirmed prior
      observations and identified five morphological categories of astrocytes: linear,
      wedge, elongate, semicircular, and circular. Each category had a unique
      sublaminar distribution across the olfactory bulb, although categories could
      occur in more than one lamina. Between 0 and 21 days postnatal a 6th category was
      apparent, radial glial cells. The mature astrocyte morphologies did not emerge
      uniformly. Astrocytes found in the outermost glomerular layer developed first
      with the appearance of the linear, wedge and elongate morphologies. Deeper
      laminate of the olfactory bulb followed in a successive fashion until the adult
      pattern was evident around 15 days postnatal. As radial glia disappeared, the
      mature morphologies assumed their final position. The data suggest that the
      maturation of olfactory bulb astrocytes may be linked to the final migration and
      maturation of olfactory bulb neurons.

PMID- 8873974
TI  - Growth conditions influence DNA methylation in cultured cerebellar granule cells.
AB  - Growth conditions influenced DNA methylation in cultured cerebellar granule
      cells, as indicated by immunocytochemical analysis with monoclonal antibodies
      raised against 5-methylcytidine. In cultures grown under suboptimal conditions,
      i.e. in medium containing 10 instead of 25 mM K+, a substantial reduction in both
      the number of immunopositive cells and the intensity of immunostaining occurred
      at 4 days in vitro (DIV), a time which preceded the appearance of the
      morphological features of apoptosis. These results suggest that a reduction in
      DNA methylation is one of the biochemical events associated with the 'condemned
      phase' of apoptosis, in which granule cells grown under suboptimal conditions
      become committed to death.

PMID- 8873975
TI  - In vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development
      in transgenic mice: evidence that IGF-I increases proliferation of granule cell
      progenitors.
AB  - The in vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum
      development have been investigated in transgenic (Tg) mice (IGF-II/I Tg mice) in
      whom an IGF-II promoter-driven IGF-I transgene is highly expressed in cerebellum.
      Compared to normal littermates, the brains of IGF-II/I Tg mice exhibited
      overgrowth beginning from the second week of postnatal life. Among the brain
      regions examined, cerebellum exhibited the greatest increase in size, such that
      by 50 days of age cerebellar weight and DNA content were increased by 90% and
      143%, respectively, compared to littermate controls. Morphological studies of
      adult IGF-II/I Tg mice showed that the total number of granule and Purkinje cells
      was increased by 82% and 20%, respectively, findings consistent with the
      increased cerebellar DNA content and indicating that the increased cerebellar
      weight was due in part to an increase in cell number. The thickness of the
      molecular layer also was increased in IGF-II/I Tg mice. During early postnatal
      development the number of external granular layer cells, as well as the number of
      BrdU labeled external granular cells, was increased. These data strongly indicate
      that IGF-I increases granule cell number by a mechanism that involves the
      stimulation of granule cell progenitor proliferation. Our findings also indicate
      that IGF-I influences the growth of Purkinje cells and possibly of other cell
      types in the cerebellum.

PMID- 8873976
TI  - Retrograde fluorescent double-labeling study of bilaterally projecting retinal
      ganglion cells in albino rats at different stages of development.
AB  - Injection of the fluorescent tracers 10% Evans blue (EB) and 4% fluoro-gold (FG)
      into the right and the left dorsal lateral geniculate nucleus, respectively, of
      albino rats at different stages of development demonstrated the presence of
      double-labeled retinal ganglion cells that projected bilaterally into both the
      dorsal lateral geniculate nuclei (dLGN). Findings confirmed that the distribution
      of these double-labeled cells was gradually reduced after birth, being confined
      to the peripheral temporoventral quarter (temporal-ventral crescent) of the
      retina after postnatal day 15. We estimated the proportion of double-labeled
      cells to total labeled cells in the same area at different stages of development
      (0-90 days); values ranged from 35.3% in the neonate to 5.27% in the adult rat
      which suggests that the majority of double-labeled cells and/or their axons were
      lost early in development. That a small number of ganglion cells were observed to
      project bilaterally in the adult rats suggested that these cells conduct the same
      visual information to both hemispheres throughout the animal's life.

PMID- 8873977
TI  - GABA and GABA-A receptors are maximally expressed in association with cone
      synaptogenesis in neonatal rabbit retina.
AB  - Previous studies have shown the cone photoreceptors form reciprocal synapses with
      horizontal cells during the first week after birth in rabbits. These synapses
      constitute pioneering elements of the developing outer plexiform layer. We now
      report that antibodies against the alpha-1 and against the beta-2/3 subunits of
      the GABA-A receptor label a highly restricted sublamina in the developing outer
      plexiform layer known to contain nascent cone photoreceptor terminals. Staining
      is relatively weak at birth, increases to maximal levels between postnatal days 5
      and 7, and is significantly reduced in the adult. These results support recent
      calcium imaging studies which have shown that the activation of GABA-A receptors
      causes an increase in intracellular free calcium in cones, an effect which is
      observed only at 3-9 days after birth. The transient expression of GABA-A
      receptors in this region coincides with the period of peak expression of GABA
      immunoreactivity in horizontal cells. A direct functional link between GABAergic
      transmission and cone synaptogenesis is suggested by previous reports that GABA-A
      receptor antagonists cause disruption of cone synaptogenesis. Together these
      findings support the notion that GABA functions as a developmental
      neurotransmitter which is produced by horizontal cells and interacts with
      developing cone axons in order to facilitate synaptic linkage between these two
      cells types.

PMID- 8873978
TI  - Crossed projection neurons are generated prior to uncrossed projection neurons in
      the lateral superior olive of the rat.
AB  - The present study examined in the lateral superior olive (LSO) of the rat whether
      LSO neurons projecting to the ipsilateral inferior colliculus (IC) might be
      generated later than those projecting to the contralateral IC. Rat fetuses were
      exposed in utero to 5-bromodeoxyuridine (BrdU), a thymidine analogue, to label
      neurons proliferating at different embryonic stages from day E11 through to E20.
      Upon reaching adulthood, the rats were given unilateral injections of fluoro-gold
      (FG), a retrograde fluorescent tracer, into the IC. Subsequently, the tissue
      sections of the brains obtained from the rats were immunostained for BrdU to
      simultaneously detect neurons that were BrdU-positive and/or FG-positive. BrdU
      positive LSO neurons were found in the rats which had been exposed to BrdU during
      E12-E16. In E12 and E13 BrdU-exposure cases, the vast majority of doubled-labeled
      (BrdU-positive and FG-positive) neurons were seen on the contralateral side to
      the FG injection. In E14, E15 and E16 BrdU-exposure cases, in contrast, all
      double-labeled neurons were found on the ipsilateral side to the FG injection.
      The distribution of these double-labeled neurons within the nucleus was diffuse
      in all the BrdU-exposure cases. Thus, the results indicate that LSO neurons are
      generated during E12-E16, that the crossed projection neurons are generated 1-4
      days earlier than the uncrossed projection neurons, and that no topographical
      relationships exist between the early- and the late-generated populations of the
      LSO neurons.

PMID- 8873979
TI  - Prostaglandin-H synthase-1 (PGHS-1) gene is expressed in specific neurons of the
      brain of the late gestation ovine fetus.
AB  - Prostaglandin (PG) E2 acts on the brain stem to modulate breathing activity in
      the ovine fetus. The source of this PGE2 is unknown and we hypothesized that it
      is produced locally in the developing brain and functions in a paracrine and/or
      autocrine manner. The purpose of the present study was to establish whether
      prostaglandin-H synthase-1 (PGHS-1), a crucial enzyme in de novo prostaglandin
      synthesis, is present and its gene expressed in the ovine fetal brain.
      Immunohistochemical and molecular hybridization techniques were used to identify
      sites of PGHS-1 immunoreactivity and PGHS-1 mRNA expression respectively in the
      brain of the ovine fetus in late gestation (approximately 126 days gestation,
      term 145 days). PGHS-1 immunoreactivity was localized to specific regions of the
      fetal brain, including the cortex, hypothalamus, hippocampal formation, superior
      colliculus of the midbrain, parabrachial nucleus of the pons, and the reticular
      formation, raphe, nucleus of the solitary tract, and gracile and cuneate nuclei
      of the medulla. The relative abundance of PGHS-1 mRNA in selected brain regions,
      as determined by Northern blot analysis, correlated qualitatively with the number
      of PGHS-1 immunoreactive neurons identified in each region. In situ hybridization
      demonstrated PGHS-1 mRNA to be localized in the same neurons or nuclei as PGHS-1
      immunoreactivity. These results indicate that PGHS-1 synthesized de novo in many
      brain regions including two that are important in respiratory control: the
      pneumotaxic center (parabrachial nucleus) and the dorsal respiratory group
      (nucleus tractus solitarius) suggesting that prostaglandins that modulate fetal
      respiratory activity are synthesized endogenously.

PMID- 8873980
TI  - Distribution of GAP-43 mRNA in the immature and adult cerebellum: a role for GAP
      43 in cerebellar development and neuroplasticity.
AB  - Expression of GAP-43 mRNA in the rat cerebellum and inferior olivary nucleus was
      examined at birth, during postnatal development and in the adult by both Northern
      and in situ hybridization. Northern blot analysis revealed that cerebellar GAP-43
      mRNA expression increases from birth to postnatal day (PD) 7 and then declines to
      a lower level in the adult. At birth, in situ hybridization experiments showed
      intense labeling of GAP-43 mRNA in the premigratory, but not the germinal, zone
      of the cerebellar external granule cell layer. Localization of GAP-43 within the
      premigratory zone, a layer containing post-mitotic granule cells, indicates that
      granule cells begin expressing GAP-43 mRNA after final mitosis and during axonal
      outgrowth of the parallel fibers. The deep cerebellar nuclei and the inferior
      olive were also intensely labeled at birth. GAP-43 mRNA was localized in granule
      cells during their migration through the molecular layer of the developing
      cerebellum and after their arrival in the internal granule cell layer. By PD 21,
      the pattern of GAP-43 expression was similar to that observed in the adult; GAP
      43 mRNA was localized to the internal granule layer and the inferior olive with
      minimal to no hybridization in the deep cerebellar nuclei and none in the
      molecular layer. Purkinje cells were devoid of GAP-43 mRNA throughout the
      postnatal and adult periods. In light of our observations, we propose that GAP-43
      is a critical factor in granule cell differentiation/migration, as well as in the
      parallel and climbing fiber axonal outgrowth and synaptogenesis during
      development. Localization of GAP-43 mRNA within granule and inferior olivary
      cells of adult animals indicates that GAP-43 protein observed in the molecular
      layer is transported from these cells to their terminals in the molecular layer
      suggesting that GAP-43 is also an intrinsic presynaptic determinant in cerebellar
      neuroplasticity.

PMID- 8873981
TI  - Patchy distribution of substance P receptor immunoreactivity in the' developing
      rat striatum.
AB  - Developmental changes of the distribution pattern of substance P receptor (SPR)
      were investigated immunohistochemically in the rat striatum. The SPR
      immunoreactivity in the striatum first emerged at postnatal day 1 and transiently
      showed a patchy pattern of distribution until it displayed the adult pattern of
      homogeneous distribution by the third postnatal week. The SPR-immunoreactivity
      patches were most marked in the medial and dorsolateral parts of the striatum, as
      well as in the subcallosal streak. They matched tyrosine hydroxylase-enriched
      areas and, conversely, avoided calbindin-enriched zones. No neurons within the
      SPR-immunoreactive patches contained either choline acetyltransferase or
      somatostatin, which is known to be contained in intrinsic neurons in the
      striatum. The vast majority of SPR-immunoreactive patch neurons also contained
      DARPP-32, a phosphoprotein that is expressed in striatal projection neurons with
      D1 dopamine receptor. The results indicate that SPR-immunoreactive patches which
      appear transiently in the developing striatum are in register with the striatal
      patch compartment, and that SPR immunoreactivity within these patches may be
      expressed on projection neurons rather than intrinsic neurons. Such SPR
      immunoreactivity in projection neurons in striatal patches may fade out in
      adulthood.

PMID- 8873982
TI  - Postnatal methadone exposure doe not prevent prenatal methadone-induced changes
      in striatal cholinergic neurons.
AB  - On postnatal day 4, rats exposed to methadone prenatally but fostered to control
      dams, as well as those fostered to dams treated with methadone, exhibited
      significant reductions in striatal acetylcholine (ACh) content. This suggests
      that neonatal withdrawal from methadone is not responsible for the effects of
      prenatal exposure on cholinergic development in the early perinatal period. The
      effects of perinatal exposure to methadone on serotonin (5HT) and dopamine (DA)
      metabolism do not appear to be strictly related to changes in ACh content.
      Although prenatal exposure reduces 5-hydroxyindole acetic acid (5HIAA) content,
      changes in 5HT content prevent significant changes in the ratio 5HIAA/5HT. Pups
      exposed to methadone only prenatally (withdrawal group) exhibited a decreased
      DOPAC/DA ratio, whereas pups in the treatment group exposed to methadone both pre
      and postnatally exhibited an increased DOPAC/DA ratio.

PMID- 8873983
TI  - Impaired cyclic AMP production in the hippocampus of a Down syndrome murine
      model.
AB  - Behavioral and learning disturbances have been found in mice with partial trisomy
      16, a new model for Down syndrome. Basal production of cyclic AMP in the
      hippocampus of trisomic mice was shown to be impaired. In addition, the responses
      of adenylyl cyclase to the stimulation of beta-adrenoceptors with isoprenaline
      and of the catalytic subunit with forskolin were both severely depressed.

PMID- 8873984
TI  - Ontogeny of the peptidergic fibers in the male mouse submandibular gland.
AB  - The first appearance of substance P (SP), calcitonin gene-related peptide (CGRP),
      vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), galanin (GAL),
      leucine-enkephalin (1-ENK), and methionine-enkephalin (m-ENK) in the male mouse
      submandibular glands were different for each. VIP immunoreactive fibers first
      appeared on embryonic day 15 (E15), SP on E16, and CGRP fibers on E18. GAL, 1
      ENK, and m-ENK fibers appeared in the early postnatal period, and NPY fibers
      occurred on postnatal day 21 (P21). From P0 to P21, VIP fibers rapidly increased
      in number, but SP and CGRP fibers increased only slightly. After P21, VIP, SP,
      and CGRP fibers decreased in number. ENK fibers were found only from P0 to P14.
      The number of these immunoreactive fibers in the adult phase was low in
      comparison with that in early postnatal phase. Around the blood vessels, SP, VIP,
      CGRP, NPY, and GAL fibers appeared by at least P7. These findings suggested that
      the transient high activity of VIP, CGRP, SP, and GAL and the transient
      appearance of ENKs in the nerve fibers may be related to the cell proliferation
      and differentiation of the functionally important structures of the mouse
      submandibular glands, and that the peptidergic innervation around the vasculature
      is probably involved in controlling local glandular circulation.

PMID- 8873985
TI  - Ontogenetic development of the response to anandamide and delta 9
      tetrahydrocannabinol in mice.
AB  - We studied the ontogenetic response to cannabinoid receptor ligands by measuring
      motor activity and analgesia in response to anandamide or delta 9-THC from day 6
      of age. No response to anandamide was observed up to the age of weaning (day 23),
      while a nonsignificant response to delta 9-THC was observed starting between days
      15 and 20. This is compatible with observations that children respond to the
      antiemetic effects of THC without psychotropic side effects.

PMID- 8873986
TI  - Ultrastructural study of ensheathing cells in early development of olfactory
      axons.
AB  - Ultrastructural observations in the grey short-tailed opossum (Monodelphis
      domestica) and rat revealed that ensheathing cells were intimately related to the
      early formation of olfactory axons. Whilst the axons were still in the olfactory
      epithelium, they were enveloped by ensheathing cell processes which formed a
      cradle-like structure on the basal side of the epithelium. Continued downgrowth
      of the axons towards the lamina propria resulted in an evagination with the
      ensheathing cell process or cell body in direct contact with the basal lamina.
      Subsequently the basal lamina became fragmented, and the newly formed olfactory
      nerve emerged from the olfactory epithelium. As the olfactory nerve grew, it was
      observed that the ensheathing cell process always extended ahead of the axons
      while axon terminals moving ahead of ensheathing cells were never observed. The
      findings in this study suggest that ensheathing cells play a role in regulating
      and promoting olfactory axon growth.

PMID- 8873987
TI  - A spontaneously immortalized mouse microglial cell line expressing CD4.
AB  - We have derived a microglial clone, named C8-B4, from the 8-day mouse cerebellum
      organ culture which gave rise to distinct astroglial cell lines as previously
      reported. Indeed, the C8-B4 clone expresses classical microglial markers (MAC1,
      F4/80, 2-4G2) and appears to be derived from a committed microglial precursor
      since it does not express differentiation antigens present during the early stage
      of the monocytic lineage. This microglial clone expresses two characteristics not
      previously reported for microglial cell lines: it synthesizes the CD4 molecule
      and produces and releases large amounts of glutamate.

PMID- 8873988
TI  - Entorhinal axons perforate hippocampal field CA3 in organotypic slice culture.
AB  - In growing towards their hippocampal targets, incoming afferent axons from the
      entorhinal cortex arrive at the subicular pole of the hippocampus and normally
      turn pialwards from the alvear path, crossing (perforating) the subiculum and
      field CA1, but never the more distally situated field CA3. To address the
      question of whether a specific repulsive characteristic of field CA3 might
      explain this behaviour, artificial confrontation were set up in vitro. Embryonic
      entorhinal explants were placed in restricted contact with 8-day-old rat
      hippocampal slices, orientated so that outgrowing axons could only grow into
      either the dentate gyrus, the subiculum/field CA1, or field CA3. Anterograde
      biotin-dextran labelling of projections after 2 weeks in culture showed that
      entorhinal axons perforated the stratum oriens, pyramidal cell layer, and stratum
      radiatum of CA3 just as readily as they did along their normal trajectory across
      CA1/subiculum. It is therefore concluded that spatiotemporal cues are more likely
      than specific chemorepulsive molecules to be involved in setting up this part of
      the entorhinal pathway.

PMID- 8873989
TI  - Release of secretory vesicle contents: regulation after fusion?

PMID- 8873990
TI  - Electrostatic coupling between retinal isomerization and the ionization state of
      Glu-204: a general mechanism for proton release in bacteriorhodopsin.
AB  - The pKa values of ionizable groups that lie between the active site region of
      bacteriorhodopsin (bR) and the extracellular surface of the protein are reported.
      Glu-204 is found to have an elevated pKa in the resting state of bR, suggesting
      that it corresponds to the proton-releasing group in bR. Its elevated pKa is
      predicted to be due in part to strong repulsive interactions with Glu-9.
      Following trans-cis isomerization of the retinal chromophore and the transfer of
      a proton to Asp-85, polar groups on the protein are able to interact more
      strongly with the ionized state of Glu-204, leading to a substantial reduction of
      its pKa. This suggests a general mechanism for proton release in which
      isomerization and subsequent charge separation initially produce a new
      electrostatic balance in the active site of bR. Here it is proposed that those
      events in turn drives a conformational change in the protein in which the ionized
      state of Glu-204 can be stabilized through interactions with groups that were
      previously inaccessible. Whether these groups should be identified with polar
      moieties in the protein, bound waters, or Arg-82 is an important mechanistic
      question whose elucidation will require further study.

PMID- 8873991
TI  - Ab initio molecular dynamics study of proton transfer in a polyglycine analog of
      the ion channel gramicidin A.
AB  - Proton transfer in biological systems is thought to often proceed through
      hydrogen-bonded chains of water molecules. The ion channel, gramicidin A (gA),
      houses within its helical structure just such a chain. Using the density
      functional theory based ab initio molecular dynamics Car-Parrinello method, the
      structure and dynamics of proton diffusion through a polyglycine analog of the gA
      ion channel has been investigated. In the channel, a proton, which is initially
      present as hydronium (H3O+), rapidly forms a strong hydrogen bond with a nearest
      neighbor water, yielding a transient H5O2+ complex. As in bulk water, strong
      hydrogen bonding of this complex to a second neighbor solvation shell is required
      for proton transfer to occur. Within gA, this second neighbor shell included not
      only a channel water molecule but also a carbonyl of the channel backbone. The
      present calculations suggest a transport mechanism in which a priori carbonyl
      solvation is a requirement for proton transfer.

PMID- 8873992
TI  - Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal
      hydrate.
AB  - The grand canonical ensemble Monte Carlo molecular simulation method is used to
      investigate hydration patterns in the crystal hydrate structure of the
      dCpG/proflavine intercalated complex. The objective of this study is to show by
      example that the recently advocated grand canonical ensemble simulation is a
      computationally efficient method for determining the positions of the hydrating
      water molecules in protein and nucleic acid structures. A detailed molecular
      simulation convergence analysis and an analogous comparison of the theoretical
      results with experiments clearly show that the grand ensemble simulations can be
      far more advantageous than the comparable canonical ensemble simulations.

PMID- 8873994
TI  - Spontaneous vesicle formation at lipid bilayer membranes.
AB  - Unilamellar vesicles are observed to form spontaneously at planar lipid bilayers
      agitated by exothermic chemical reactions. The membrane-binding reaction between
      biotin and streptavidin, two strong transmembrane neutralization reactions, and a
      weak neutralization reaction involving an "antacid" buffer, all lead to
      spontaneous vesicle formation. This formation is most dramatic when a viscosity
      differential exists between the two phases bounding the membrane, in which case
      vesicles appear exclusively in the more viscous phase. A hydrodynamic analysis
      explains the phenomenon in terms of a membrane flow driven by liberated reaction
      energy, leading to vesicle formation. These results suggest that energy liberated
      by intra- and extracellular chemical reactions near or at cell and internal
      organelle membranes can play an important role in vesicle formation, membrane
      agitation, or enhanced transmembrane mass transfer.

PMID- 8873993
TI  - Locations of local anesthetic dibucaine in model membranes and the interaction
      between dibucaine and a Na+ channel inactivation gate peptide as studied by 2H-
      and 1H-NMR spectroscopies.
AB  - To study the molecular mechanisms of local anesthesia, locations of local
      anesthetic dibucaine in model membranes and the interactions of dibucaine with a
      Na+ channel inactivation gate peptide have been studied by 2H- and 1H-NMR
      spectroscopies. The 2H-NMR spectra of dibucaine-d9 and dibucaine-d1, which are
      deuterated at the butoxy group and at the 3 position in its quinoline ring,
      respectively, have been observed in multilamellar dispersions of the lipid
      mixture composed of phosphatidylcholine, phosphatidylserine, and
      phosphatidylethanolamine. 2H-NMR spectra of deuterated palmitic acids
      incorporated, as a probe, into the lipid mixture containing cholesterol have also
      been observed. An order parameter, SCD, for each carbon segment was calculated
      from the observed quadrupole splittings. Combining these results, we concluded
      that first, the butoxy group of dibucaine is penetrating between the acyl chains
      of lipids in the model membranes, and second, the quinoline ring of dibucaine is
      located at the polar region of lipids but not at the hydrophobic acyl chain
      moiety. These results mean that dibucaine is situated in a favorable position
      that permits it to interact with a cluster of hydrophobic amino acids (Ile-Phe
      Met) within the intracellular linker between domains III and IV of Na+ channel
      protein, which functions as an inactivation gate. To confirm whether the
      dibucaine molecule at the surface region of lipids can really interact with the
      hydrophobic amino acids, we synthesized a model peptide that includes the
      hydrophobic amino acids (Ac-GGQDIFMTEEQK-OH, MP-1), the amino acid sequence of
      which corresponds to the linker part of rat brain type IIA Na+ channel, and the
      one in which Phe has been substituted by Gln (MP-2), and measured 1H-NMR spectra
      in both phosphate buffer and phosphatidylserine liposomes. It was found that the
      quinoline ring of dibucaine can interact with the aromatic ring of Phe by
      stacking of the rings; moreover, the interaction can be reinforced by the
      presence of lipids. In conclusion, we wish to propose that local anesthesia
      originates from the pi-stacking interaction between aromatic rings of an
      anesthetic molecule located at the polar headgroup region of the so-called
      boundary lipids and of the Phe in the intracellular linker between domains III
      and IV of the Na+ channel protein, prolonging the inactivated state and
      consequently making it impossible to proceed to the resting state.

PMID- 8873995
TI  - Crystal structure of the self-complementary 5'-purine start decamer d(GCGCGCGCGC)
      in the Z-DNA conformation. I.
AB  - Alternating self-complementary oligonucleotides starting with a 5'-pyrimidine
      usually form left-handed Z-DNA; however, with a 5'-purine start sequence they
      form the right-handed A-DNA. Here we report the crystal structure of the decamer
      d(GCGCGCGCGC) with a 5'-purine start in the Z-DNA form. The decamer crystallizes
      in the hexagonal space group P6(5)22, unit cell dimensions a = b = 18.08 and c =
      43.10 A, with one of the following four dinucleotide diphosphates in the
      asymmetric unit: d(pGpC)/d(GpCp)/d(pCpG)/d(CpGp). The molecular replacement
      method, starting with d(pGpC) of the isomorphous Z-DNA hexamer d(araC-dG)3
      without the 2'-OH group of arabinose, was used in the structure analysis. The
      method gave the solution only after the sugar-phosphate conformation of the GpC
      step was manipulated. The refinement converged to a final R value of 18.6% for
      340 unique reflections in the resolution range 8.0-1.9 A. A result of the
      sequence alternation is the alternation in the nucleotide conformation; guanosine
      is C3'-endo, syn, and cytidine is C2'-endo, anti. The CpG step phosphodiester
      conformation is the same as ZI or ZII, whereas that of the GpC step
      phosphodiester is "intermediate" in the sense that zeta (O3'-P bond) is the same
      as ZII but alpha (P-O5' bond) is the same as ZI. The duplexes generated from the
      dinucleotide asymmetric unit are stacked one on top of the other in the crystal
      to form an infinite pseudocontinuous helix. This renders it a quasi-polymerlike
      structure that has assumed the Z-DNA conformation further strengthened by the
      long inner Z-forming stretch d(CG)4. An interesting feature of the structure is
      the presence of water strings in both the major and the minor grooves. In the
      minor groove the cytosine carbonyl oxygen atoms of the GpC and CpG steps are
      cross-bridged by water molecules that are not themselves hydrogen bonded but are
      enclosed by the water rings in the mouth of the minor groove. In the major groove
      three independent water molecules form a zigzagging continuous water string that
      runs throughout the duplex.

PMID- 8873996
TI  - Crystal structure of the self-complementary 5'-purine start decamer d(GCACGCGTGC)
      in the A-DNA conformation. II.
AB  - The crystal structure of the alternating 5'-purine start decamer d(GCGCGCGCGC)
      was found to be in the left-handed Z-DNA conformation. Inasmuch as the A.T base
      pair is known to resist Z-DNA formation, we substituted A.T base pairs in the
      dyad-related positions of the decamer duplex. The alternating self-complementary
      decamer d(GCACGCGTGC) crystallizes in a different hexagonal space group, P6(1)22,
      with very different unit cell dimensions a = b = 38.97 and c = 77.34 A compared
      with the all-G.C alternating decamer. The A.T-containing decamer has one strand
      in the asymmetric unit, and because it is isomorphous to some other A-DNA
      decamers it was considered also to be right-handed. The structure was refined,
      starting with the atomic coordinates of the A-DNA decamer d(GCGGGCCCGC), by use
      of 2491 unique reflections out to 1.9-A resolution. The refinement converged to
      an R value of 18.6% for a total of 202 nucleotide atoms and 32 water molecules.
      This research further demonstrates that A.T base pairs not only resist the
      formation of Z-DNA but can also assist the formation of A-DNA by switching the
      helix handedness when the oligomer starts with a 5'-purine; also, the length of
      the inner Z-DNA stretch (d(CG)n) is reduced from an octamer to a tetramer. It may
      be noted that these oligonucleotide properties are in crystals and not
      necessarily in solutions.

PMID- 8873997
TI  - Mechanism and size cutoff for steric exclusion from actin-rich cytoplasmic
      domains.
AB  - Subdomains of the cytoplasmic volume in tissue culture cells exclude large tracer
      particles relative to small. Evidence suggests that exclusion of the large
      particles is due to molecular sieving by the dense meshwork of microfilaments
      found in these compartments, but exclusion as a result of the close apposition of
      the dorsal and ventral plasma membrane of the cell in these regions has not been
      ruled out conclusively. In principle, these two mechanisms can be distinguished
      by the dependence of exclusion on tracer particle size. By fluorescence ratio
      imaging we have measured the partition coefficient (P/PO) into excluding
      compartments for tracer particles ranging in radius from 1 to 41 nm. The decay of
      P/PO as a function of particle radius is better fitted by three molecular sieving
      models than by a slit pore model. The sieving models predict a percolation cutoff
      radius of the order of 50 nm for partitioning into excluding compartments.

PMID- 8873998
TI  - Motor protein mechanics: a stochastic model with minimal mechanochemical
      coupling.
AB  - A stochastic model for the action of motor proteins such as kinesin is presented.
      The mechanical components of the enzyme are 1) two identical head domains that
      bind to discrete sites on a microtubule and that are capable of undergoing a
      conformational change; and 2) an elastic element that connects each head to the
      rest of the molecule. We investigate the situation in which the strain dependence
      of the chemical reaction rates is minimal and the heads have independent
      biochemical cycles. The enzyme advances stochastically along a filament when one
      head detaches and diffuses to a new binding site, while the other head remains
      bound to the microtubule. We also investigate the case in which the chemical
      cycles of the heads are correlated so that the molecule shifts each head
      alternately. The predictions of the model are found to be in agreement with
      experimentally measured force-velocity relationships for kinesin-both when the
      force is applied externally and when the enzyme is loaded by a viscous drag. For
      reasonable values of the parameters, this agreement is quantitative. The
      molecular stepping characteristics observed in recent motility assays are also
      reproduced. A number of experiments are suggested that would provide a more
      stringent test of the model and help determine whether this simple picture is an
      appropriate description of motor proteins or whether models that include strain
      dependent reaction rates or more complicated types of cooperation of the two
      heads need to be considered.

PMID- 8873999
TI  - Insertion and hairpin formation of membrane proteins: a Monte Carlo study.
AB  - Some particular effects of a lipid membrane on the partitioning and the
      concomitant folding processes of model proteins have been investigated using
      Monte Carlo methods. It is observed that orientational order and lateral density
      fluctuations of the lipid matrix stabilize the orientation of helical proteins
      and induce a tendency of spontaneous formation of helical hairpins for helices
      longer than the width of the membrane. The lateral compression of the lipids on a
      hairpin leads to the extrusion of a loop at the trans side of the membrane. The
      stability of the hairpin can be increased by the design of appropriate groups of
      hydrophilic and hydrophobic residues at the extruded loop. It is shown that in
      the absence of lipids the orientation of proteins is not stable and the formation
      of hairpins is absent. Some analogies between the formation of helical hairpins
      in membranes and the formation of hairpins in polymer liquid crystals are
      discussed. The simulations indicate that the insertion process follows a well
      defined pattern of kinetic steps.

PMID- 8874000
TI  - A mathematical description of miniature postsynaptic current generation at
      central nervous system synapses.
AB  - Variation in the amplitude of miniature postsynaptic currents (mPSCs) generated
      by individual quanta of neurotransmitter is a major contributor to the variance
      of evoked synaptic responses. Here we explore the possible origins of this
      variability by developing a mathematical description of mPSC generation and
      consider the contribution of "off-center" release to this variability. By "off
      center" release we mean variation in the distance between the position where a
      presynaptic vesicle discharges its content of neurotransmitter into the synaptic
      cleft and the center of a cluster of postsynaptic receptors (PRCs) that responds
      to those transmitter molecules by generating an mPSC. We show that when the time
      course of quantal discharge through a fusion pore (noninstantaneous release) is
      considered, elementary analytical descriptions of the subsequent diffusion of
      transmitter within the synaptic cleft (with or without uptake) predict the
      development of significant gradients of transmitter concentration during the
      rising phase of mPSCs. This description of diffusion is combined with a
      description of the pharmacodynamics of receptors in the PRC and of the time
      dependence of the gradient of transmitter concentration over the area of the PRC
      to reconstruct the time course and amplitude of an mPSC for a synapse of a given
      geometry. Within the constraints of known dimensions of presynaptic active zones
      and postsynaptic receptor clusters at CNS synapses, our analysis suggests that
      "off-center" release, produced by allowing release to occur anywhere within an
      anatomically defined presynaptic active zone, can be an important contributor to
      mPSC variability. Indeed, modulation of the influence of "off-center" release may
      be a novel way of controlling synaptic efficacy. We also show how
      noninstantaneous release can serve to focus the action of neurotransmitter within
      a given synapse and thereby reduce cross-talk between synapses.

PMID- 8874001
TI  - Formation of ordered domains in membrane-bound DNA.
AB  - The interactions between DNA molecules adsorbed on fluid membranes are
      calculated. The adsorbing DNA perturbs the equilibrium packing of the lipids,
      thereby giving rise to membrane-induced, attractive interactions. These balance
      the direct repulsive interactions between DNA molecules. As a result, DNA
      adsorbed on membranes is predicted to form ordered domains characterized by a
      finite spacing, which varies with the membrane characteristics and the solution
      Debye screening length. Comparing the model predictions to recent experiments
      (Yang et al. 1996) yields excellent agreement with only one free (i.e.,
      experimentally unknown) parameter.

PMID- 8874002
TI  - PH regulation of connexin43: molecular analysis of the gating particle.
AB  - Gap junction channels allow for the passage of ions and small molecules between
      neighboring cells. These channels are formed by multimers of an integral membrane
      protein named connexin. In the heart and other tissues, the most abundant
      connexin is a 43-kDa, 382-amino acid protein termed connexin43 (Cx43). A
      characteristic property of connexin channels is that they close upon
      acidification of the intracellular space. Previous studies have shown that
      truncation of the carboxyl terminal of Cx43 impairs pH sensitivity. In the
      present study, we have used a combination of optical, electrophysiological, and
      molecular biological techniques and the oocyte expression system to further
      localize the regions of the carboxyl terminal that are involved in pH regulation
      of Cx43 channels. Our results show that regions 261-300 and 374-382 are essential
      components of a pH-dependent "gating particle," which is responsible for
      acidification-induced uncoupling of Cx43-expressing cells. Regions 261-300 and
      374-382 seem to be interdependent. The function of region 261-300 may be related
      to the presence of a poly-proline repeat between amino acids 274 and 285.
      Furthermore, site-directed mutagenesis studies show that the function of region
      374-382 is not directly related to its net balance of charges, although mutation
      of only one amino acid (aspartate 379) for asparagine impairs pH sensitivity to
      the same extent as truncation of the carboxyl terminal domain (from amino acid
      257). The mutation in which serine 364 is substituted for proline, which has been
      associated with some cases of cardiac congenital malformations in humans, also
      disrupts the pH gating of Cx43, although deletion of amino acids 364-373 has no
      effect on acidification-induced uncoupling. These results provide new insight
      into the molecular mechanisms responsible for acidification-induced uncoupling of
      gap junction channels in the heart and in other Cx43-expressing structures.

PMID- 8874003
TI  - Single-channel analysis of inactivation-defective rat skeletal muscle sodium
      channels containing the F1304Q mutation.
AB  - The intracellular linker between domains III and IV of the voltage-gated Na
      channel mediates fast inactivation. Targeted alteration of one or more of a
      triplet of hydrophobic amino acids within this linker region results in a marked
      slowing in the decay of ionic current. The mechanism of this defective
      inactivation was explored in rat skeletal muscle sodium channels (mu 1)
      containing the F1304Q mutation in Xenopus laevis oocytes with and without
      coexpression of the rat brain beta 1 subunit. Cell-attached single-channel patch
      clamp recordings revealed that the mu 1-F1304Q channel reopens multiple times
      with open times that are prolonged compared with those of the wild-type channel.
      Coexpression of the beta 1 subunit stabilized a dominant nonbursting gating mode
      and accelerated the activation kinetics of mu 1-F1304Q but did not modify mean
      open time or fast-inactivation kinetics. A Markov gating model incorporating
      separate fast- and slow-inactivation particles reproduced the results by assuming
      that the F1304Q mutation specifically influences transitions to and from fast
      inactivated states. These effects are independent of interactions of the mutant
      channel with the beta 1 subunit and do not result from a change in modal gating
      behavior. These results indicate that F1304Q mutant channels can still enter the
      inactivated state but do so reversibly and with altered kinetics.

PMID- 8874004
TI  - Use dependence of tetrodotoxin block of sodium channels: a revival of the trapped
      ion mechanism.
AB  - The use-dependent block of sodium channels by tetrodotoxin (TTX) has been studied
      in cRNA-injected Xenopus oocytes expressing the alpha-subunit of rat brain IIA
      channels. The kinetics of stimulus-induced extra block are consistent with an
      underlying relaxation process involving only three states. Cumulative extra block
      induced by repetitive stimulations increases with hyperpolarization, with TTX
      concentration, and with extracellular Ca2+ concentration. We have developed a
      theoretical model based on the suggestion by Salgado et al. that TTX blocks the
      extracellular mouth of the ion pore less tightly when the latter has its external
      side occupied by a cation, and that channel opening favors a tighter binding by
      allowing the escape of the trapped ion. The model provides an excellent fit of
      the data, which are consistent with Ca2+ being more efficient than Na+ in
      weakening TTX binding and with bound Ca2+ stabilizing the closed state of the
      channel, as suggested by Armstrong and Cota. Reports arguing against the trapped
      ion mechanism are critically discussed.

PMID- 8874005
TI  - Interaction between ion channel-inactivating peptides and anionic phospholipid
      vesicles as model targets.
AB  - Studies of rapid (N-type) inactivation induced by different synthetic
      inactivating peptides in several voltage-dependent cation channels have concluded
      that the channel inactivation "entrance" (or "receptor" site for the inactivating
      peptide) consists of a hydrophobic vestibule within the internal mouth of the
      channel, separated from the cytoplasm by a region with a negative surface
      potential. These protein domains are conformed from alternative sequences in the
      different channels and thus are relatively unrestricted in terms of primary
      structure. We are reporting here on the interaction between the inactivating
      peptide of the Shaker B K+ channel (ShB peptide) or the noninactivating ShB-L7E
      mutant with anionic phospholipid vesicles, a model target that, as the channel's
      inactivation "entrance," contains a hydrophobic domain (the vesicle bilayer)
      separated from the aqueous media by a negatively charged vesicle surface. When
      challenged by the anionic phospholipid vesicles, the inactivating ShB peptide 1)
      binds to the vesicle surface with a relatively high affinity, 2) readily adopts a
      strongly hydrogen-bonded beta-structure, likely an intramolecular beta "hairpin,"
      and 3) becomes inserted into the hydrophobic bilayer by its folded N-terminal
      portion, leaving its positively charged C-terminal end exposed to the
      extravesicular aqueous medium. Similar experiments carried out with the
      noninactivating, L7E-ShB mutant peptide show that this peptide 1) binds also to
      the anionic vesicles, although with a lower affinity than does the ShB peptide,
      2) adopts only occasionally the characteristic beta-structure, and 3) has
      completely lost the ability to traverse the anionic interphase at the vesicle
      surface and to insert into the hydrophobic vesicle bilayer. Because the
      negatively charged surface and the hydrophobic domains in the model target may
      partly imitate those conformed at the inactivation "entrance" of the channel
      proteins, we propose that channel inactivation likely includes molecular events
      similar to those observed in the interaction of the ShB peptide with the
      phospholipid vesicles, i.e., binding of the peptide to the region of negative
      surface potential, folding of the bound peptide as a beta-structure, and its
      insertion into the channel's hydrophobic vestibule. Likewise, we relate the lack
      of channel inactivation seen with the mutant ShB-L7E peptide to the lack of
      ability shown by this peptide to cross through the anionic interphase and insert
      into the hydrophobic domains of the model vesicle target.

PMID- 8874006
TI  - Voltage-clamp studies of gap junctions between uterine muscle cells during term
      and preterm labor.
AB  - Gap junctions between myometrial cells increase dramatically during the final
      stages of pregnancy. To study the functional consequences, we have applied the
      double-whole-cell voltage-clamp technique to freshly isolated pairs of cells from
      rat circular and longitudinal myometrium. Junctional conductance was greater
      between circular muscle-cell pairs from rats delivering either at term (32 +/- 16
      nS, mean +/- SD, n = 128) or preterm (26 +/- 17 nS, n = 33) compared with normal
      preterm (4.7 +/- 7.6 nS, n = 114) and postpartum (6.5 +/- 10 nS, n = 16); cell
      pairs from the longitudinal layer showed similar differences. The macroscopic gap
      junction currents decayed slowly from an instantaneous, constant-conductance
      level to a steady-state level described by quasisymmetrical Boltzmann functions
      of transjunctional voltage. In half of circular-layer cell pairs, the voltage
      dependence of myometrial gap junction conductance is more apparent at smaller
      transjunctional voltages (< 30 mV) than for other tissues expressing mainly
      connexin-43. This unusual degree of voltage dependence, although slow, operates
      over time intervals that are physiologically relevant for uterine muscle. Using
      weakly coupled pairs, we observed two unitary conductance states: 85 pS (85-90%
      of events) and 25 pS. These measurements of junctional conductance support the
      hypothesis that heightened electrical coupling between the smooth muscle cells of
      the uterine wall emerges late in pregnancy, in preparation for the massive,
      coordinate contractions of labor.

PMID- 8874007
TI  - A biophysical model for defibrillation of cardiac tissue.
AB  - We propose a new model for electrical activity of cardiac tissue that
      incorporates the effects of cellular microstructure. As such, this model provides
      insight into the mechanism of direct stimulation and defibrillation of cardiac
      tissue after injection of large currents. To illustrate the usefulness of the
      model, numerical stimulations are used to show the difference between successful
      and unsuccessful defibrillation of large pieces of tissue.

PMID- 8874008
TI  - Commentary: surface tension of biomembranes.

PMID- 8874009
TI  - What is the surface tension of a lipid bilayer membrane?

PMID- 8874010
TI  - On simulating lipid bilayers with an applied surface tension: periodic boundary
      conditions and undulations.
AB  - As sketched in Fig. 1, a current molecular dynamics computer simulation of a
      lipid bilayer fails to capture significant features of the macroscopic system,
      including long wavelength undulations. Such fluctuations are intrinsically
      connected to the value of the macroscopic (or thermodynamic) surface tension (cf.
      Eqs. 1 and 9; for a related treatment, see Brochard et al., 1975, 1976).
      Consequently, the surface tension that might be evaluated in an MD simulation
      should not be expected to equal the surface tension obtained from macroscopic
      measurements. Put another way, the largest of the three simulations presented
      here contained over 16,000 atoms and required substantial computer time to
      complete, but modeled a system of only 36 lipids per side. From this perspective
      it is not surprising that the system is not at the thermodynamic limit. An
      important practical consequence of this effect is that simulations with
      fluctuating area should be carried out with a nonzero applied surface tension
      (gamma 0 of Fig. 2) even when the macroscopic tension is zero, or close to zero.
      Computer simulations at fixed surface area, which can explicitly determine
      pressure anisotropy at the molecular level, should ultimately lend insight into
      the value of gamma 0, including its dependence on lipid composition and other
      membrane components. As we have noted and will describe further in separate
      publications (Feller et al., 1996; Feller et al., manuscript in preparation),
      surface tensions obtained from simulations can be distorted by inadequate initial
      conditions and convergence, and are sensitive to potential energy functions,
      force truncation methods, and system size; it is not difficult, in fact, to tune
      terms in the potential energy function so as to yield surface tensions close to
      zero. This is why parameters should be tested extensively on simpler systems, for
      example, monolayers. The estimates of gamma 0 that we have presented here should
      be regarded as qualitative, and primarily underscore the assertion that the
      surface tension of a microscopically flat, simulation-sized patch is
      significantly greater than zero. As the simulation cell length increases, the
      surface tension that would be evaluated (or should be applied) decreases; in the
      limit of micrometer-sized simulation cells, gamma would approach zero or its
      appropriate thermodynamic value. The theories presented here also imply that the
      estimation of bilayer surface tension from monolayer data should take the degree
      of flatness into account. These conclusions are independent of the precise values
      of parameters such as bending constants. In conclusion, from the simulator's
      perspective, the question "What is the surface tension of a bilayer?" is better
      phrased as "What is the value of the applied surface tension necessary to
      simulate a particular experimental system with a given number of lipids?". As we
      have shown, the answer to the second question varies, but it should not be
      assumed a priori to equal zero.

PMID- 8874011
TI  - Spontaneous formation of interfacial lipid-protein monolayers during adsorption
      from vesicles.
AB  - Spread and adsorbed monolayers of lipid-protein mixtures have served as models
      for biomembranes and pulmonary surfactant, but their similarity was unclear.
      Epifluorescence microscopy of monolayers spontaneously adsorbed from vesicles of
      dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylcholine plus surfactant
      protein C (SP-C) showed gas, liquid expanded, and liquid condensed (LC) domains.
      The shapes and distribution of LC domains in the adsorbed and solvent-spread
      monolayers were quite similar. Labeled SP-C adsorbed into the air-water interface
      in the company of the lipids. In both forms of monolayers, SP-C occupied the
      fluid phase and reduced the size and amount of the LC domains. The properties
      suggest that these adsorbed and spread monolayers are analogous to one another.

PMID- 8874012
TI  - Lateral diffusion in planar lipid bilayers: a fluorescence recovery after
      photobleaching investigation of its modulation by lipid composition, cholesterol,
      or alamethicin content and divalent cations.
AB  - In spite of the fact that planar lipid bilayers are still the best-suited
      artificial membrane system for the study of reconstituted ion channels and
      receptors, data dealing with their physical characterization, especially as
      regards dynamics, are scanty. A combined electrical and optical chamber was
      designed and allowed fluorescence recovery after photobleaching recovery curves
      to be recorded from stable virtually solvent-free bilayers. D, the lateral
      diffusion coefficient of N-(7-nitrobenzoyl-2-oxa-1,3-diazol-4-yl)-1,2
      dihexadecanoyl-sn- glycero-3-phosphoethanolamine, was found to be relatively
      insensitive to the phospholipid composition (headgroup, chain unsaturation,
      etc.), whereas inclusion of 33-50% cholesterol in the membrane reduced D by a
      factor of 2. Divalent cations significantly reduced D of negatively charged
      bilayers. These results compare well with data gathered on other model and
      natural systems. In addition, the incorporation of the voltage-dependent pore
      former alamethicin did slightly reduce lipid lateral mobility. This study
      demonstrates the feasibility of such experiments with planar bilayers, which are
      amenable to physical constraints, and thus offers new opportunities for
      systematic studies of structure-function relationships in membrane-associating
      molecules.

PMID- 8874014
TI  - Phase behavior of stratum corneum lipids in mixed Langmuir-Blodgett monolayers.
AB  - The lipids found in the bilayers of the stratum corneum fulfill the vital barrier
      role of mammalian bodies. The main classes of lipids found in stratum corneum are
      ceramides, cholesterol, and free fatty acids. For an investigation of their phase
      behavior, mixed Langmuir-Blodgett monolayers of these lipids were prepared.
      Atomic force microscopy was used to investigate the structure of the monolayers
      as a function of the monolayer composition. Three different types of ceramide
      were used: ceramide extracted from pigskin, a commercially available ceramide
      with several fatty acid chain lengths, and two synthetic ceramides that have only
      one fatty acid chain length. In pigskin ceramide-cholesterol mixed monolayers
      phase separation was observed. This phase separation was also found for the
      commercially available type III Sigma ceramide-cholesterol mixed monolayers with
      molar ratios ranging from 1:0.1 to 1:1. These monolayers separated into two
      phases, one composed of the long fatty acid chain fraction of Sigma ceramide III
      and the other of the short fatty acid chain fraction of Sigma ceramide III mixed
      with cholesterol. Mixtures with a higher cholesterol content consisted of only
      one phase. These observations were confirmed by the results obtained with
      synthetic ceramides, which have only one fatty acid chain length. The synthetic
      ceramide with a palmitic acid (16:0) chain mixed with cholesterol, and the
      synthetic ceramide with a lignoceric acid (24:0) chain did not. Free fatty acids
      showed a preference to mix with one of these phases, depending on their fatty
      acid chain lengths. The results of this investigation suggest that the model
      system used in this study is in good agreement with those of other studies
      concerning the phase behavior of the stratum corneum lipids. By varying the
      composition of the monolayers one can study the role of each lipid class in
      detail.

PMID- 8874013
TI  - Accelerated interleaflet transport of phosphatidylcholine molecules in membranes
      under deformation.
AB  - Biological membranes are lamellar structures composed of two leaflets capable of
      supporting different mechanical stresses. Stress differences between leaflets
      were generated during micromechanical experiments in which long thin tubes of
      lipid (tethers) were formed from the surfaces of giant phospholipid vesicles. A
      recent dynamic analysis of this experiment predicts the relaxation of local
      differences in leaflet stress by lateral slip between the leaflets. Differential
      stress may also relax by interleaflet transport of lipid molecules ("flip-flop").
      In this report, we extend the former analysis to include interleaflet lipid
      transport. We show that transmembrane lipid flux will evidence itself as a linear
      increase in tether length with time after a step reduction in membrane tension.
      Multiple measurements were performed on 24 different vesicles composed of
      stearoyl-oleoyl-phosphatidylcholine plus 3% dinitrophenol-linked di-oleoyl
      phosphatidylethanolamine. These tethers all exhibited a linear phase of growth
      with a mean value of the rate of interlayer permeation, cp = 0.009 s-1. This
      corresponds to a half-time of approximately 8 min for mechanically driven
      interleaflet transport. This value is found to be consistent with longer times
      obtained for chemically driven transport if the lipids cross the membrane via
      transient, localized defects in the bilayer.

PMID- 8874015
TI  - Oriented 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine/ganglioside membranes: a
      Fourier transform infrared attenuated total reflection spectroscopic study. Band
      assignments; orientational, hydrational, and phase behavior; and effects of Ca2+
      binding.
AB  - Fourier transform infrared (FTIR) attenuated total reflection (ATR) spectroscopy
      was used to elucidate the hydration behavior and molecular order of
      phospholipid/ganglioside bilayers. We examined dry and hydrated films of the
      gangliosides GM1, deacetyl-GM1, lyso-GM1, deacetyllyso-GM1, and GM3 and oriented
      mixed films of these gangliosides with 1,2-dimyristoyl-sn-glycero-3
      phosphorylcholine (DMPC) using polarized light. Analysis of the amide I
      frequencies reveals that the amide groups are involved in intermolecular
      interactions via hydrogen bonds of varying strengths. The tilt angle of the acyl
      chains of the lipids in mixed films was determined as a function of ganglioside
      structure. Deacetylation of the sialic acid in the headgroup has a stronger
      influence on the tilt angle than the removal of the ganglioside fatty acid. The
      phase behavior was examined by FTIR ATR spectroscopy and by differential scanning
      calorimetry (DSC) measurements on lipid suspensions. At the same molar
      concentration, lyso-gangliosides have less effect on changes of transition
      temperature compared to the double-chain analogs. Distinct differences in the
      amide band shapes were observed between mixtures with lyso-gangliosides and
      normal double-chain gangliosides. Determined from the dicroic ratio RATR, the
      orientation of the COO- group in all DMPC/ganglioside mixtures was found to be
      relatively fixed with respect to the membrane normal. In 4:1 mixtures of DMPC
      with GM1 and deacetyl-GM1, the binding of Ca2+ leads to a slight decrease in
      chain tilt in the gel phase, probably caused by a dehydration of the membrane
      water interface. In mixtures of DMPC with GM3 and deacetyl-lyso-GM1, a slight
      increase in chain tilt is observed. The chain tilt in DMPC/lyso-GM1 mixtures is
      unchanged. Analysis of the COO- band reveals that Ca2+ does not bind to the
      carboxylate group of the sialic acid of GM1 and deacetyl-GM1, the mixtures in
      which a decrease in chain tilt was observed. Binding to the sialic acid was only
      observed for mixtures of DMPC with GM3, lyso-GM1, and deacetyl-lyso-GM1. Ca2+
      obviously accumulates at the bilayer-water interface and leads to partial
      dehydration of the headgroup region in the gel as well as in the liquid
      crystalline phase. This can be concluded from the changes in the amide I band
      shapes. With the exception of DMPC/deacetyl-GM1, the effects on the ester C==O
      bands are small. The addition of Ca2+ has minor effects on the phase behavior,
      with the exception of the DMPC/GM1 mixture.

PMID- 8874016
TI  - Preferential partitioning of melittin into the air/water interface: structural
      and thermodynamic implications.
AB  - The membrane active agent melittin has been investigated with regard to the
      formation of a Langmuir monolayer and the accordingly induced surface activities.
      We show that in spite of its considerable solubility in an aqueous medium, this
      peptide nevertheless largely accumulates in the air/water interface unless the
      lateral pressure is raised beyond a certain threshold value depending on the pH
      in the subphase. The true surface concentrations have been determined by means of
      a recently developed novel method based on thermodynamic principles. It affords
      an access to the partitioning equilibrium between the surface and subphase
      domains, provided the latter surrounding is not excessively preferred. In the
      present case this approach was used to derive quantitative information on the
      pertinent interfacial structure and thermodynamics. In particular, the apparent
      molecular area and the Gibbs energy of mutual interaction in the monolayer could
      be evaluated as a function of the applied surface pressure. The data suggest the
      existence of two structural conversions in the course of an increasing lateral
      compression. The surface-associated peptide accordingly assumes three different
      states of successively reduced area requirements, supposedly owing to an
      orientational transition involving a straightening up of a helical conformation.
      This conclusion is corroborated by surface potential measurements reflecting
      corresponding changes of the effective dipole moment perpendicular to the
      surface.

PMID- 8874017
TI  - Distribution and diffusivity of a hydrophobic probe molecule in the interior of a
      membrane: theory and simulation.
AB  - We propose a simple model for the distribution of position and orientation and
      the diffusion of a hydrophobic probe molecule embedded in a membrane. The
      molecule experiences both a Maier-Saupe orienting potential as well as an
      enclosing potential of repulsion from the membrane walls. A statistical
      thermodynamics treatment of the model provides predictions of the location and
      orientation of the molecule within the membrane. In particular, we evaluate the
      order parameter of the molecule in terms of the model constants. The diffusivity
      of the probe is studied by Brownian dynamics simulation. For rotational
      diffusion, we check an available analytical approximate treatment that allows for
      the prediction of the dynamics in terms of equilibrium quantities. We also pay
      attention to quantities related to the initial and mean reorientational rate of
      the probe. For translational diffusion, we use the simulation results to analyze
      some general aspects of lateral and transversal diffusion.

PMID- 8874018
TI  - Thermotropic properties of phosphatidylethanols.
AB  - Phosphatidylethanol is formed when ethanol substitutes in the
      transphosphatidylation reaction catalyzed by phospholipase D. The structural and
      thermotropic properties of dipalmitoylphosphatidylethanol and
      dimyristoylphosphatidylethanol have been studied using differential scanning
      calorimetry, fluorescence spectroscopy, and 31P nuclear magnetic resonance. These
      lipids exist in a bilayer phase with no indication of nonbilayer phase formation,
      as shown by 31P nuclear magnetic resonance. It was found that the phase behavior
      of these phospholipids before and during the main chain melting transition is
      different in 50 mM Tris buffer compared to salt solutions. The phase transition
      behavior and the 6-propionyl-2-(dimethylamino)naphthalene (Prodan) fluorescence
      spectra for both lipids are consistent with the formation of the interdigitated
      gel phase under certain conditions. Both lipids become interdigitated in Tris
      HCl, and ethanol enhances the formation of this phase. Comparative studies of the
      6-propionyl-2-(dimethylamino)naphthalene spectra in
      dipalmitoylphosphatidylglycerol, dielaidoylphosphatidylethanolamine, and
      dipalmitoylphosphatidylcholine further elucidate the value and limitations of
      this probe as a diagnostic tool for lipid structure.

PMID- 8874019
TI  - Effects of MgATP and MgADP on the cross-bridge kinetics of rabbit soleus slow
      twitch muscle fibers.
AB  - The elementary steps surrounding the nucleotide binding step in the cross-bridge
      cycle were investigated with sinusoidal analysis in rabbit soleus slow-twitch
      muscle fibers. The single-fiber preparations were activated at pCa 4.40, ionic
      strength 180 mM, 20 degrees C, and the effects of MgATP (S) and MgADP (D)
      concentrations on three exponential processes B, C, and D were studied. Our
      results demonstrate that all apparent (measured) rate constants increased and
      saturated hyperbolically as the MgATP concentration was increased. These results
      are consistent with the following cross-bridge scheme: [cross-bridge scheme: see
      text] where A = actin, M = myosin, S = MgATP, and D = MgADP. AM+S is a collision
      complex, and AM*S is its isomerized form. From our studies, we obtained K0 = 18
      +/- 4 mM-1 (MgADP association constant, N = 7, average +/- sem), K1a = 1.2 +/-
      0.3 mM-1 (MgATP association constant, N = 8 hereafter), k1b = 90 +/- 20 s-1 (rate
      constant of ATP isomerization), k-1b = 100 +/- 9 s-1 (rate constant of reverse
      isomerization), K1b = 1.0 +/- 0.2 (equilibrium constant of isomerization), k2 =
      21 +/- 3 s-1 (rate constant of cross-bridge detachment), k-2 = 14.1 +/- 1.0 s-1
      (rate constant of reversal of detachment), and K2 = 1.6 +/- 0.3 (equilibrium
      constant of detachment). K0 is 8 times and K1a is 2.2 times those in rabbit
      psoas, indicating that nucleotides bind to cross-bridges more tightly in soleus
      slow-twitch muscle fibers than in psoas fast-twitch muscle fibers. These results
      indicate that cross-bridges of slow-twitch fibers are more resistant to ATP
      depletion than those of fast-twitch fibers. The rate constants of ATP
      isomerization and cross-bridge detachment steps are, in general, one-tenth to one
      thirtieth of those in psoas.

PMID- 8874020
TI  - Mechanical and structural properties underlying contraction of skeletal muscle
      fibers after partial 1-ethyl-3-[3-dimethylamino)propyl]carbodiimide cross
      linking.
AB  - We show prolonged contraction of permeabilized muscle fibers of the frog during
      which structural order, as judged from low-angle x-ray diffraction, was preserved
      by means of partial cross-linking of the fibers using the zero-length cross
      linker 1-ethyl-3-[3-dimethylamino)propyl]carbodiimide. Ten to twenty percent of
      the myosin cross-bridges were cross-linked, allowing the remaining 80-90% to
      cycle and generate force. These fibers displayed a well-preserved sarcomeric
      order and mechanical characteristics similar to those of intact muscle fibers.
      The intensity of the brightest meridional reflection at 14.5 nm, resulting from
      the projection of cross-bridges evenly spaced along the myofilament length,
      decreased by 60% as a relaxed fiber was deprived of ATP and entered the rigor
      state. Upon activation of a rigorized fiber by the addition of ATP, the intensity
      of this reflection returned to 97% of the relaxed value, suggesting that the
      overall orientation of cross-bridges in the active muscle was more perpendicular
      to the filament axis than in rigor. Following a small-amplitude length step
      applied to the active fibers, the reflection intensity decreased for both
      releases and stretches. In rigor, however, a small stretch increased the
      amplitude of the reflection by 35%. These findings show the close link between
      cross-bridge orientation and tension changes.

PMID- 8874021
TI  - On the theory of muscle contraction: filament extensibility and the development
      of isometric force and stiffness.
AB  - The newly discovered extensibility of actin and myosin filaments challenges the
      foundation of the theory of muscle mechanics. We have reformulated A. F. Huxley's
      sliding filament theory to explicitly take into account filament extensibility.
      During isometric force development, growing cross-bridge tractions transfer loads
      locally between filaments, causing them to extend and, therefore, to slide
      locally relative to one another. Even slight filament extensibility implies that
      1) relative displacement between the two must be nonuniform along the region of
      filament overlap, 2) cross-bridge strain must vary systematically along the
      overlap region, and importantly, 3) the local shortening velocities, even at
      constant overall sarcomere length, reduce force below the level that would have
      developed if the filaments had been inextensible. The analysis shows that an
      extensible filament system with only two states (attached and detached) displays
      three important characteristics: 1) muscle stiffness leads force during force
      development; 2) cross-bridge stiffness is significantly higher than previously
      assessed by inextensible filament models; and 3) stiffness is prominently
      dissociated from the number of attached cross-bridges during force development.
      The analysis also implies that the local behavior of one myosin head must depend
      on the state of neighboring attachment sites. This coupling occurs exclusively
      through local sliding velocities, which can be significant, even during isometric
      force development. The resulting mechanical cooperativity is grounded in fiber
      mechanics and follows inevitably from filament extensibility.

PMID- 8874023
TI  - Constructing optimal backbone segments for joining fixed DNA base pairs.
AB  - A method is presented to link a sequence of space-fixed base pairs by the sugar
      phosphate segments of single nucleotides and to evaluate the effects in the
      backbone caused by this positioning of the bases. The entire computational unit
      comprises several nucleotides that are energy-minimized, subject to constraints
      imposed by the sugar-phosphate backbone segments being anchored to space-fixed
      base pairs. The minimization schemes are based on two stages, a conjugate
      gradient method followed by a Newton-Raphson algorithm. Because our purpose is to
      examine the response, or relaxation, of an artificially stressed backbone, it is
      essential to be able to obtain, as closely as possible, a lowest minimum energy
      conformation of the backbone segment in conformational space. For this purpose,
      an algorithm is developed that leads to the generation of an assembly of many
      local energy minima. From these sets of local minima, one conformation
      corresponding to the one with the lowest minimum is then selected and designated
      to represent the backbone segment at its minimum. The effective electrostatic
      potential of mean force is expressed in terms of adjustable parameters that
      incorporate solvent screening action in the Coulombic interactions between
      charged backbone atoms; these parameters are adjusted to obtain the best fit of
      the nearest-neighbor phosphorous atoms in an x-ray structure.

PMID- 8874022
TI  - The bundling of actin with polyethylene glycol 8000 in the presence and absence
      of gelsolin.
AB  - Actin filament and bundle formation occur in the cytosol under conditions of very
      high total macromolecular concentration. In this study we have utilized the inert
      molecule polyethylene glycol 8000 (PEG) as a means of simulating crowded
      conditions in vitro. Column-purified Ca-actin was polymerized in the absence and
      presence of gelsolin (to regulate mean filament lengths between 50 and 5000 mers)
      and PEG (2-8%) using various concentrations of KCl and/or 2 mM divalent cations.
      Bundling was characterized by the scattered light intensity and mean diffusion
      coefficients obtained from dynamic light scattering, as well as by fluorescence
      and phase-contrast microscopy. The minimum concentration of KCl required for
      bundling decreases both with increasing concentration of PEG at a fixed mean
      filament length, and with decreasing filament length at a fixed concentration of
      PEG. In the absence of divalent cation, bundling is reversible on dilution, as
      determined by intensity levels, diffusion coefficients, and microscopy. However,
      with either 2 mM Mg2+ or Ca2+ added, bundling is irreversible under conditions of
      higher PEG concentrations or longer filaments, indicating that osmotic pressure
      effects cannot fully explain actin bundling with PEG. Weaker divalent cation
      binding sites on actin as well as disulfide bonds appear to be involved in the
      irreversible bundling.

PMID- 8874024
TI  - Interdependence of conformational variables in double-helical DNA.
AB  - DNA exhibits conformational polymorphism, with the details depending on the
      sequence and its environment. To understand the mechanisms of conformational
      polymorphism and these transitions, we examine the interrelationships among the
      various conformational variables of DNA. In particular, we examine the stress
      strain relation among conformational variables, describing base-pair morphology
      and their effects on the backbone conformation. For the calculation of base
      pairs, we use the method previously developed to calculate averages over
      conformational variables of DNA. Here we apply this method to calculate the
      Boltzmann averages of conformational variables for fixed values of one particular
      conformational variable, which reflects the strain in the structure responding to
      a particular driving stress. This averaging over all but one driving variable
      smooths the usual rough energy surface to permit observation of the effects of
      one conformational variable at a time. The stress-strain analyses of
      conformational variables of base pair slide, twist, and roll, which exhibit
      characteristic changes during the conformational transition of DNA, have shown
      that the conformational changes of base pairs are strongly correlated with one
      another. Furthermore, the stress-strain relations are not symmetrical with
      respect to these variables, i.e., the response of one coordinate to another is
      different from the reverse direction. We also examine the effect of
      conformational changes in base-pair variables on the sugar-backbone conformation
      by using the minimization method we developed. The conformational changes of base
      pairs affect the sugar pucker and other dihedral angles of the backbone of DNA,
      but each variable affects the sugar-backbone differently. In particular, twist is
      found to have the most influence in affecting the sugar pucker and backbone
      conformation. These calculated conformational changes in base pairs and backbone
      segments are consistent with experimental observations and serve to validate the
      calculation method.

PMID- 8874025
TI  - 23Na NMR study of the effect of organic osmolytes on DNA counterion atmosphere.
AB  - The effect of different organic osmolytes on the DNA counterion condensation
      layer has been investigated by 23Na NMR relaxation measurements. The zwitterionic
      compounds glycine, beta-alanine, 4-aminobutyric acid, and 6-aminocaproic acid
      have shown an increasing capacity to decrease the amount of sodium ions in the
      vicinity of the macromolecule. The experimental data have been correlated with
      the dielectric constant increase in their corresponding solutions and have been
      compared with the prediction of counterion condensation theory. Polyols (sorbitol
      and mannitol) did not display the same effect. These compounds largely increase
      the relaxation rate of sodium ions in the proximity of DNA, unlike the
      zwitterionic compounds. This probably results from a perturbation of the water
      dynamic around the macromolecule, of the primary or secondary hydration shell of
      the sodium nuclei involved, or both.

PMID- 8874027
TI  - Is there an error correcting code in the base sequence in DNA?
AB  - Modern methods of encoding information into digital form include error check
      digits that are functions of the other information digits. When digital
      information is transmitted, the values of the error check digits can be computed
      from the information digits to determine whether the information has been
      received accurately. These error correcting codes make it possible to detect and
      correct common errors in transmission. The sequence of bases in DNA is also a
      digital code consisting of four symbols: A, C, G, and T. Does DNA also contain an
      error correcting code? Such a code would allow repair enzymes to protect the
      fidelity of nonreplicating DNA and increase the accuracy of replication. If a
      linear block error correcting code is present in DNA then some bases would be a
      linear function of the other bases in each set of bases. We developed an
      efficient procedure to determine whether such an error correcting code is present
      in the base sequence. We illustrate the use of this procedure by using it to
      analyze the lac operon and the gene for cytochrome c. These genes do not appear
      to contain such a simple error correcting code.

PMID- 8874026
TI  - Comparison of the solution and crystal conformations of (G + C)-rich fragments of
      DNA.
AB  - DNA fragments crystallize in an unpredictable manner, and relationships between
      their crystal and solution conformations still are not known. We have studied,
      using circular dichroism spectroscopy, solution conformations of (G + C)-rich DNA
      fragments, the crystal structures of which were solved in the laboratory of one
      of the present authors. In aqueous trifluorethanol (TFE) solutions, all of the
      examined oligonucleotides adopted the same type of double helix as in the
      crystal. Specifically, the dodecamer d(CCCCCGCGGGGG) crystalized as A-DNA and
      isomerized into A-DNA at high TFE concentrations. On the other hand, the hexamer
      d(CCGCGG) crystallized in Z-form containing tilted base pairs, and high TFE
      concentrations cooperatively transformed it into the same Z-form as adopted by
      the RNA hexamer r(CGCGCG), although d(CCGCGG) could isomerize into Z-DNA in the
      NaCl + NiCl2) aqueous solution. The fragments crystallizing as B-DNA remained B
      DNA, regardless of the solution conditions, unless they denatured or aggregated.
      Effects on the oligonucleotide conformation of 2-methyl-2,4-pentanediol and other
      crystallization agents were also studied. 2-Methyl-2,4-pentanediol induced the
      same conformational transitions as TFE but, in addition, caused an
      oligonucleotide condensation that was also promoted by the other crystallization
      agents. The present results indicate that the crystal double helices of DNA are
      stable in aqueous TFE rather than aqueous solution.

PMID- 8874028
TI  - Catalysis of the retinal subpicosecond photoisomerization process in acid purple
      bacteriorhodopsin and some bacteriorhodopsin mutants by chloride ions.
AB  - The dynamics and the spectra of the excited state of the retinal in
      bacteriorhodopsin (bR) and its K-intermediate at pH 0 was compared with that of
      bR and halorhodopsin at pH 6.5. The quantum yield of photoisomerization in acid
      purple bR was estimated to be at least 0.5. The change of pH from 6.5 to 2 causes
      a shift of the absorption maximum from 568 to 600 nm (acid blue bR) and decreases
      the rate of photoisomerization. A further decrease in pH from 2 to 0 shifts the
      absorption maximum back to 575 nm when HCl is used (acid purple bR). We found
      that the rate of photoisomerization increases when the pH decreases from 2 to 0.
      The effect of chloride anions on the dynamics of the retinal photoisomerization
      of acid bR (pH 2 and 0) and some mutants (D85N, D212N, and R82Q) was also
      studied. The addition of 1 M HCl (to make acid purple bR, pH 0) or 1 M NaCl to
      acid blue bR (pH 2) was found to catalyze the rate of the retinal
      photoisomerization process. Similarly, the addition of 1 M NaCl to the solution
      of some bR mutants that have a reduced rate of retinal photoisomerization (D85N,
      D212N, and R82Q) was found to catalyze the rate of their retinal
      photoisomerization process up to the value observed in wild-type bR. These
      results are explained by proposing that the bound Cl- compensates for the loss of
      the negative charges of the COO- groups of Asp85 and/or Asp212 either by
      neutralization at low pH or by residue replacement in D85N and D212N mutants.

PMID- 8874029
TI  - Effects of sequential stimuli on Halobacterium salinarium photobehavior.
AB  - We analyzed the motor photoresponses of Halobacterium salinarium to different
      test stimuli applied after a first photophobic response produced by a step-down
      of red-orange light (prestimulus). We observed that pulses given with a suitable
      delay after the prestimulus produced unusual responses. Pulses of blue, green, or
      red-orange light, each eliciting no response when applied alone, produced a
      secondary photophobic response when applied several seconds after the
      prestimulus; the same occurred with a negative blue pulse (rapid shut-off and
      turning on of a blue light). Conversely, no secondary photophobic response was
      observed when the test stimulus was a step (a step-up for red-orange light, a
      step-down for blue light) of the same wavelength and intensity. When the delay
      was varied, different results were obtained with different wavelengths; red
      orange pulses were typically effective in producing a secondary photophobic
      response, even with a delay of 2 s, whereas the response to a blue pulse was
      suppressed when the test stimulus was applied within 5 s after the prestimulus.
      The secondary photophobic response to pulses was abolished by reducing the
      intensity of the prestimulus without affecting the primary photophobic response.
      These results, some of which were previously reported in the literature as
      inverse effects, must be produced by a facilitating mechanism depending on the
      prestimulus itself, the occurrence of reversals being per se ineffective. The
      fact that red-orange test stimuli are facilitated even at the shortest delay,
      whereas those of different wavelengths become effective only after several
      seconds, suggests that the putative mechanism of the facilitating effect is
      specific for different signaling pathways.

PMID- 8874031
TI  - Structural and sequence characteristics of long alpha helices in globular
      proteins.
AB  - Elucidation of the detailed structural features and sequence requirements for
      alpha helices of various lengths could be very important in understanding
      secondary structure formation in proteins and, hence, in the protein folding
      mechanism. An algorithm to characterize the geometry of an alpha helix from its
      C(alpha) coordinates has been developed and used to analyze the structures of
      long alpha helices (number of residues > or = 25) found in globular proteins, the
      crystal structure coordinates of which are available from the Brookhaven Protein
      Data Bank. All long alpha helices can be unambiguously characterized as belonging
      to one of three classes: linear, curved, or kinked, with a majority being curved.
      Analysis of the sequences of these helices reveals that the long alpha helices
      have unique sequence characteristics that distinguish them from the short alpha
      helices in globular proteins. The distribution and statistical propensities of
      individual amino acids to occur in long alpha helices are different from those
      found in short alpha helices, with amino acids having longer side chains and/or
      having a greater number of functional groups occurring more frequently in these
      helices. The sequences of the long alpha helices can be correlated with their
      gross structural features, i.e., whether they are curved, linear, or kinked, and
      in case of the curved helices, with their curvature.

PMID- 8874030
TI  - Ligand binding to heme proteins. VI. Interconversion of taxonomic substates in
      carbonmonoxymyoglobin.
AB  - The kinetic properties of the three taxonomic A substates of sperm whale
      carbonmonoxy myoglobin in 75% glycerol/buffer are studied by flash photolysis
      with monitoring in the infrared stretch bands of bound CO at nu(A0) approximately
      1967 cm-1, nu(A1) approximately 1947 cm-1, and nu(A3) approximately 1929 cm-1
      between 60 and 300 K. Below 160 K the photodissociated CO rebinds from the heme
      pocket, no interconversion among the A substates is observed, and rebinding in
      each A substate is nonexponential in time and described by a different
      temperature-independent distribution of enthalpy barriers with a different
      preexponential. Measurements in the electronic bands, e.g., the Soret, contain
      contributions of all three A substates and can, therefore, be only approximately
      modeled with a single enthalpy distribution and a single preexponential. The bond
      formation step at the heme is fastest for the A0 substate, intermediate for the
      A1 substate, and slowest for A3. Rebinding between 200 and 300 K displays several
      processes, including geminate rebinding, rebinding after ligand escape to the
      solvent, and interconversion among the A substates. Different kinetics are
      measured in each of the A bands for times shorter than the characteristic time of
      fluctuations among the A substates. At longer times, fluctuational averaging
      yields the same kinetics in all three A substates. The interconversion rates
      between A1 and A3 are determined from the time when the scaled kinetic traces of
      the two substates merge. Fluctuations between A1 and A3 are much faster than
      those between A0 and either A1 or A3, so A1 and A3 appear as one kinetic species
      in the exchange with A0. The maximum-entropy method is used to extract the
      distribution of rate coefficients for the interconversion process A0 <--> A1 + A3
      from the flash photolysis data. The temperature dependencies of the A substate
      interconversion processes are fitted with a non-Arrhenius expression similar to
      that used to describe relaxation processes in glasses. At 300 K the
      interconversion time for A0 <--> A1 + A3 is 10 microseconds, and extrapolation
      yields approximately 1 ns for A1 <--> A3. The pronounced kinetic differences
      imply different structural rearrangements. Crystallographic data support this
      conclusion: They show that formation of the A0 substate involves a major change
      of the protein structure; the distal histidine rotates about the C(alpha)-C(beta)
      bond, and its imidazole sidechain swings out of the heme pocket into the solvent,
      whereas it remains in the heme pocket in the A1 <--> A3 interconversion. The fast
      A1 <--> A3 exchange is inconsistent with structural models that involve
      differences in the protonation between A1 and A3.

PMID- 8874032
TI  - Molecular diffusion into horse spleen ferritin: a nitroxide radical spin probe
      study.
AB  - Electron paramagnetic resonance spectroscopy and gel permeation chromatography
      were employed to study the molecular diffusion of a number of small nitroxide
      spin probes (approximately 7-9 A diameter) into the central cavity of the iron
      storage protein ferritin. Charge and polarity of these radicals play a critical
      role in the diffusion process. The negatively charged radical 4-carboxy-2,2,6,6
      tetramethylpiperidine-N-oxyl (4-carboxy-TEMPO) does not penetrate the cavity
      whereas the positively charged 4-amino-TEMPO and 3-(aminomethyl)-proxyl radical
      and polar 4-hydroxy-TEMPO radical do. Unlike the others, the apolar TEMPO radical
      does not enter the cavity but instead binds to ferritin, presumably at a
      hydrophobic region of the protein. The kinetic data indicate that diffusion is
      not purely passive, the driving force coming not only from the concentration
      gradient between the inside and outside of the protein but also from charge
      interactions between the diffusant and the protein. A model for diffusion is
      derived that describes the observed kinetics. First-order half-lives for
      diffusion into the protein of 21-26 min are observed, suggesting that reductant
      molecules with diameters considerably larger than approximately 9 A would
      probably enter the protein cavity too slowly to mobilize iron efficiently by
      direct interaction with the mineral core.

PMID- 8874033
TI  - Nanosecond time-resolved absorption studies of human oxyhemoglobin photolysis
      intermediates.
AB  - The time-resolved spectra of photoproducts from ligand photodissociation of
      oxyhemoglobin are measured in the Soret spectral region for times from 10 ns to
      320 microseconds after laser photolysis. Four processes are detected at a heme
      concentration of 80 microM: a 38-ns geminate recombination, a 137-ns tertiary
      relaxation, and two bimolecular processes for rebinding of molecular oxygen. The
      pseudo-first-order rate constants for rebinding to the alpha and beta subunits of
      hemoglobin are 3.2 x 10(4) s-1 (31 microseconds lifetime) and 9.4 x 10(4) s-1 (11
      microseconds lifetime), respectively. The significance of kinetic measurements
      made at different heme concentrations is discussed in terms of the equilibrium
      compositions of hemoglobin tetramer and dimer mixtures. The rebinding rate
      constants for alpha and beta chains are observed to be about two times slower in
      the dimer than in the tetramer, a finding that appears to support the observation
      of quaternary enhancement in equilibrium ligand binding by hemoglobin tetramers.

PMID- 8874034
TI  - Stability of the dystrophin rod domain fold: evidence for nested repeating units.
AB  - An examination of fragments of the human dystrophin rod domain, corresponding to
      a single structural repeating unit, showed that a critical chain length, defined
      with a precision of one residue at the C-terminal end, is required for formation
      of the native tertiary fold. We report here that extending the chain by six
      residues beyond this minimum results in a large increase in conformational
      stability. This is not related to a change in association state of the
      polypeptide. The results support the conjecture that successive repeating units
      in the rod domain of the spectrinlike proteins form a nested structure, in which
      the N-terminal part of the three-helix bundle of one repeat packs into the
      overlapping structure of the preceding repeat. This would be expected to affect
      functional characteristics related to flexibility of the dystrophin rod domain.

PMID- 8874035
TI  - Hydrodynamic examination of the dimeric cytoplasmic domain of the human
      erythrocyte anion transporter, band 3.
AB  - Solution studies of the cytoplasmic domain (molecular mass approximately 40kDa)
      of band 3, the anion exchanger from human erythrocyte membranes, previously
      suggested a dimeric molecule on the basis of the relative techniques of
      calibrated gel filtration and calibrated preparative ultracentrifugation. This
      dimeric behavior is firmly established on an absolute basis by a combination of
      calibrated gel chromatography and absolute ultracentrifugation techniques.
      Sedimentation velocity in the analytical ultracentrifuge combined with calibrated
      gel chromatography give a molecular mass M of (77 +/- 4) kDa, a value confirmed
      by low-speed sedimentation equilibrium. Velocity sedimentation in the analytical
      ultracentrifuge gave a single sedimenting species with an s o 20,w of (3.74 +/-
      0.07)S. Sedimentation equilibrium analysis was also used to establish the
      strength of the binding via the dissociation constant Kd, with a value from
      direct fitting of the concentration distribution curves of (2.8 +/- 0.5) microM,
      confirmed by a value of approximately 3 microM obtained from fitting a plot of
      molecular weight Mw,app versus cell loading concentration. Hydrodynamic
      calculations based on the classical translational frictional ratio showed that
      the protein was highly asymmetric, with an axial ratio of approximately 10:1,
      consistent with observations from electron microscopy.

PMID- 8874036
TI  - Infrared nonlinear optical measurements of membrane potential in photoreceptor
      cells.
AB  - In the past it has not been possible to measure optically the membrane potential
      of cells and collections of cells that are either naturally photosensitive or
      that can be activated by photolyzable caged transmitter molecules. This paper
      reports on a unique application of nonlinear optics that can monitor the
      potential of cellular membranes with a near-infrared source. Among many other
      singular advantages, this nonlinear optical approach to measuring membrane
      potential does not activate light sensitive cells or cell suspensions and
      cellular networks surrounded with photolyzable molecules. To demonstrate this
      capability we show that the technique can be applied to living photoreceptor
      cells that are very sensitive to visible light. These cells are ideal for
      characterizing such a new technique, not only because of their unmatched
      sensitivity to light, but also because their electrical responses have been
      extensively characterized (Minks and Selinger, 1992).

PMID- 8874037
TI  - Line-scanning microphotolysis for diffraction-limited measurements of lateral
      diffusion.
AB  - Fluorescence microphotolysis was combined with confocal laser-scanning microscopy
      to yield a method, herein referred to as line-scanning microphotolysis
      (LINESCAMP), for the measurement of molecular transport at a lateral resolution
      of approximately 0.34 microns and a temporal resolution of approximately 0.5 ms.
      A confocal microscope was operated in the line scan mode, while the laser beam
      power could be switched during scanning between low monitoring and high
      photolysing levels in less then a microsecond. The number and location of line
      segments to be photolysed could be freely determined. The length of the
      photolysed segments could be also chosen and was only limited by diffraction.
      Together with instrumentation a new, completely general, theoretical framework
      for the evaluation of diffusion measurements was developed. Based on the
      numerical simulation of diffusion processes employing a modified Crank-Nicholson
      scheme, the theory could be applied to any photobleaching geometry and profile as
      the initial condition and took into account the convolution with the microscope
      point spread function. With small diffraction-limited areas, the method yielded
      accurate values for diffusion coefficients in the range between approximately 10(
      4) and 1 micron2 s-1. A first application of the method to the diffusion of a
      fluorescently labeled tracer inside the cell nucleus showed the potential of the
      method for the study of complex biological systems.

PMID- 8874039
TI  - Teaching light scattering spectroscopy: the dimension and shape of tobacco mosaic
      virus.
AB  - The tobacco mosaic virus is used as a model molecular assembly to illustrate the
      basic potentialities of light scattering techniques (both static and dynamic) to
      undergraduates. The work has two objectives: a pedagogic one (introducing light
      scattering to undergraduate students) and a scientific one (stabilization of the
      virus molecular assembly structure by the nucleic acid). Students are first
      challenged to confirm the stabilization of the cylindrical shape of the virus by
      the nucleic acid, at pH and ionic strength conditions where the coat proteins
      alone do not self-assemble. The experimental intramolecular scattering factor is
      compared with the theoretical ones for several model geometries. The data clearly
      suggest that the geometry is, in fact, a rod. Comparing the experimental values
      of gyration radius and hydrodynamic radius with the theoretical expectations
      further confirms this conclusion. Moreover, the rod structure is maintained over
      a wider range of pH and ionic strength than that valid for the coat proteins
      alone. The experimental values of the diffusion coefficient and radius of
      gyration are compared with the theoretical expectations assuming the dimensions
      detected by electron microscopy techniques. In fact, both values are in agreement
      (length approximately 300 nm, radius approximately 20 nm).

PMID- 8874038
TI  - Exocytotic release from individual granules exhibits similar properties at mast
      and chromaffin cells.
AB  - The effects of temperature on granular secretion were studied in individual
      bovine adrenal chromaffin and rat peritoneal mast cells. It was found that more
      molecules are released from individual granules at physiological temperature than
      at room temperature, where such experiments are normally performed. In mast
      cells, there is also a dramatic decrease in the time required for exocytosis to
      be complete at 37 degrees C compared to room temperature. In the presence of some
      cations, the amount released from individual granules at room temperature from
      both types of cells could be altered. The amount of secretion decreased with the
      divalent cation zinc but increased with the monovalent cation cesium. These
      experiments used two electrochemical techniques: cyclic voltammetry and
      amperometry. With amperometry, the concentration gradient created by the
      electrode near the cell further increased the amount of release. Similar
      responses to changes in the extracellular environment in chromaffin and mast
      cells suggest that the mechanism of extrusion of the granule contents is similar
      in both cell types.

PMID- 8874040
TI  - Designing inhibitors of the metalloproteinase superfamily: comparative analysis
      of representative structures.
AB  - Structural comparisons of representative members of the zinc metalloproteinase
      superfamily show that the key secondary structural elements are conserved, in
      spite of major variations in the sequences including insertions and deletions of
      functional domains. Major differences between the matrix metalloproteinases
      (matrixins) are clustered in two regions forming the entrance to the active site
      and hence may be determinants of substrate selectivity. A comparison of the
      structures of matrixin-inhibitor complexes shows that there are significant
      differences even among the closely related matrixins, not only in the peripheral
      regions but also in the specificity pockets; these differences offer an excellent
      opportunity for the design of specific inhibitors targetted to individual
      members.

PMID- 8874041
TI  - Nonpeptidic potent HIV-1 protease inhibitors.
AB  - From an initial mass screening lead, (IC50: 3 microM) and information derived
      from the X-ray crystallographic structure of a related analog, complexed with HIV
      protease (PR), the design of more potent inhibitors has been advanced. Various
      structure-guided approaches to fill P1' and P2' pockets using this pyran-2-one
      template, molecular modeling and X-ray crystallographic studies led to potent
      compounds. Of particular significance to the design of this series of inhibitors
      is the displacement of key structural waters. The binding modes of a series of
      pyran-2-one analogs and comparison of binding modes with different pyran-2-ones,
      are highlighted. Noteworthy was the discovery of a highly potent (IC50: 0.007
      microM) pyran-2-one derivative, containing novel P1' and P2' functionalization
      and possessing no chiral centers and having low molecular weight. Pyran-2-ones
      possessing appended groups to reach to the S3 pocket of the enzyme via tethering
      on the 6-phenyl ring of pyran-2-one ring is also discussed.

PMID- 8874042
TI  - Targeting HIV reverse transcriptase for anti-AIDS drug design: structural and
      biological considerations for chemotherapeutic strategies.
AB  - The reverse transcriptase of HIV is a key target for the antiviral treatment of
      AIDS. Numerous potent inhibitors of RT have been described including all of the
      drugs that have been currently licensed for the treatment of AIDS, but their
      efficacy has been limited by the emergence of drug-resistant HIV variants.
      Extensive biochemical, genetic, and clinical data about HIV RT enzymatic
      mechanisms, inhibition, and drug resistance have been reported. This information,
      taken together with structural data from crystallographic studies of HIV-1 RT,
      has set the stage for structure-based design of improved inhibitors of this
      essential viral enzyme. Comparisons of the different crystal structures of HIV-1
      RT shows that the enzyme has great conformational flexibility, providing
      additional possibilities for drug targeting. Recent clinical and virological data
      suggest that HIV-1 RT enzymes that carry drug-resistance mutations can be
      substantially impaired and that combinations of RT inhibitors can produce
      significant clinical benefit in the treatment of AIDS. An immediate goal is to
      use the available information to design specific inhibitors or combination
      therapies that will select for relatively less fit HIV variants.

PMID- 8874043
TI  - Dopamine D2 receptor model explains binding affinity of neuroleptics: piquindone
      and its structure activity relationships.

PMID- 8874044
TI  - Rational design of a new C-myristylamido peptide exerting potent and selective
      PKC inhibitory activity.
AB  - A 3D model of the catalytic domain of PKC was built based on the X-ray structure
      of the homologous PKA enzyme. The two enzymes were found to have similar general
      architecture although differing for the number of negatively charged clusters and
      their location near the phosphorylation site. These differences were consistent
      with the charge requirements deduced from the consensus sequence of PKC and PKA
      substrates. A Myristyl Binding Site (MBS) was found in the PKC model between
      helix C and sheets 8 and 9. The identification of this MBS allowed the
      rationalization of the results obtained with N-myristoylated peptide inhibitors
      and, above all, the design of ITF1671 (H-RFARKGALRQKN-CONH-Myr), a new C
      myristylamido peptide, which exerted one of the most potent inhibitory activity
      against PKC and PKM known to-date.

PMID- 8874045
TI  - Hydrophobic D-amino acids in the design of peptide ligands for the pp60src SH2
      domain.
AB  - Src homology-2 (SH2) domains, containing approximately 100 amino acid residues,
      are noncatalytic motifs involved with intracellular signal transduction. These
      domains can be found on nonreceptor kinases, phosphatases, and in regulatory
      adapter proteins among others. SH2 domains bind proteins containing
      phosphotyrosine (pTyr) residues in a sequence specific manner. Our efforts have
      focused on designing peptide mimetic ligands for the SH2 domain of the
      nonreceptor tyrosine kinase pp60src. We employed the cocrystal structure of the
      11mer Glu-Pro-Gln-pTyr-Glu-Glu-Ile-Pro-IIe-Tyr-Leu IC50 = 800 nM as a starting
      point for our design efforts. These efforts have resulted in the discovery of
      tripeptide ligands containing D-amino acids that are only 2-fold less potent than
      the 11mer.

PMID- 8874047
TI  - The coiled coil stem loop miniprotein as a presentation scaffold.
AB  - The coiled coil helical dimer found in naturally occurring proteins is
      conformationally stable and can tolerate significant sequence variation on the
      solvent-exposed surfaces of the helices. We are interested in exploring the use
      of a de novo designed coiled coil stem loop miniprotein (CCSL) as a template for
      presenting (1) helical and loop sequences from heterologous proteins and (2)
      constrained libraries of peptides. Towards this end, we synthesized a 56 residue
      prototype CCSL and verified its structure by extensive biophysical
      characterization. CCSL variants with altered sequences in the solvent-exposed
      helical positions were found to fold similarly to the prototype design. Based on
      the results with the CCSL produced by peptide synthesis, we assembled a synthetic
      cDNA for the CCSL prototype and expressed the CCSL miniprotein on filamentous
      phage. This genetic construction can be used to introduce random peptide
      libraries into regions within the scaffold loop and helices in order to identify
      key side chains of native proteins involved in binding, to establish structural
      models for their pharmacophores and to identify novel peptide recognition mimics
      of macromolecular ligands and their receptors.

PMID- 8874046
TI  - Structure of the Ras-binding domain of c-Raf-1 as determined by NMR spectroscopy
      and identification of the region that interacts with Ras.
AB  - The structure of the Ras-binding domain of human c-Raf-1 (residues 55 to 132) as
      determined in solution by NMR spectroscopy is presented. It consists of a five
      stranded beta-sheet, a twelve residue alpha-helix, and an additional one-turn
      helix. The fold belongs to a known family whose members include ubiquitin and
      protein G. The surface of Raf55-132 that interacts with Ras has been identified
      by resonance perturbation mapping. The binding site is a spatially contiguous
      patch comprised of the two-N-terminal beta-strands, the loop between them, and
      the C-terminal end of the alpha-helix. A model of the Raf-Ras complex is
      presented, which was derived by analogy to the complex between protein G and a
      Fab fragment of IgG. In the model, edge beta-strands of each protein align in an
      antiparallel orientation, forming a unified beta-sheet, and side chains from both
      proteins are able to participate in ionic and hydrophobic interactions at the
      interface.

PMID- 8874048
TI  - Comparison of cyclic and linear analogs of vasoactive intestinal peptide.
AB  - A series of i-->i + 4 side-chain to side-chain lactam analogs of vasoactive
      intestinal peptide has been prepared in order to study the effect of cyclization
      on biological activity. In vitro, on guinea pig tracheal smooth muscle and on
      human bronchial tissue, approximately half of the cyclic analogs showed increased
      potency and half were decreased over the linear analogs. Several cyclic compounds
      were between 10- and 20-fold more potent and one was 290-fold more potent than
      the linear species. In vivo, in guinea pigs, the cyclic compounds showed
      increased potency by up to 70-fold and significantly enhanced duration of action
      as compared to linear compounds.

PMID- 8874049
TI  - Characterizing the DNA binding modes of a topoisomerase I-poisoning
      terbenzimidazole: evidence for both intercalative and minor groove binding
      properties.
AB  - We have used a broad range of spectroscopic and viscometric techniques to
      demonstrate that the complexation of a cytotoxic, topoisomerase I-poisoning
      terbenzimidazole (5PTB) with the poly(dA).poly(dT) duplex exhibits properties
      characteristic of both intercalation and minor groove binding. Our results reveal
      the following features: (i) Optical melting profiles reveal that 5PTB binding
      enhances the thermal stability of the poly(dA).poly(dT) duplex; (ii) Fluorescence
      detected 5PTB binding to the poly(dA).poly(dT) duplex reveals four apparent "site
      sizes," ranging from 1 to 13 base pairs (bp) per bound drug; (iii) Flow linear
      dichroism data suggest conformational heterogeneity among the poly(dA).poly(dT)
      bound 5PTB molecules, with substantial contributions from drug molecules bound in
      the minor groove; (iv) Fluorescence resonance energy transfer data reveal
      properties characteristic of a significant contribution from an intercalative
      mode of binding; (v) Viscometric, fluorescence quenching, and netropsin
      competition data are consistent with 5PTB binding to poly(dA).poly(dT) by "mixed"
      modes, which are operationally defined as single or multiple binding populations
      that individually and/or collectively express both intercalative and minor groove
      binding properties. We comment on a potential correlation between drugs that
      exhibit such "mixed" mode binding motifs and those that express antineoplastic
      activity through inhibition of topoisomerase I.

PMID- 8874050
TI  - Drug-membrane interactions studied by molecular dynamics simulation: size
      dependence of diffusion.
AB  - Bioavailability, largely due to membrane permeation, is an important step in the
      drug delivery process and therefore drug design. In this study, a series of
      molecular dynamics simulations (totaling 10's of nanoseconds) of small molecules
      (varying in size, and functional groups) in lipid bilayer membranes were used to
      elucidate the mechanism of diffusion of drugs within biomembranes. These
      simulations accurately reproduce many experimentally observed parameters. The
      simulations also agree with theory that indicates the lipid bilayer has internal
      structure that influences the diffusion process and that even within the
      hydrocarbon regions there are distinct regions between which the rate and
      mechanism of diffusion varies. In particular, in agreement with experiment and
      theory the small solutes were found to diffuse by a mechanism different from that
      of large molecules. These variations are linked to the frequency and size of
      spontaneously arising voids within the bilayer as well as the rate of torsional
      isomerization of the hydrocarbon chains.

PMID- 8874051
TI  - Validation of highly discriminating multiplex short tandem repeat amplification
      systems for individual identification.
AB  - Short tandem repeat (STR) loci are routinely employed for individual
      identification. WE have examined the performance and reproducibility of a highly
      informative co-amplification system containing the tetranucleotide STR loci:
      HUMVWFA31/A, HUMTH01, D20S85, D8S1179, HUMFIBRA, D21S11, and D18S51, in
      conjunction with the amelogenin sex test, in addition to a modified system
      omitting the locus D20S85. Polymerase chain reaction (PCR) products were
      fluorescently detected on an automated sequencer and automatically sized against
      an internal size standard by Genescan software. Both systems were routinely able
      to type 500 pg of undegraded DNA. At DNA concentrations between 50-500 pg,
      partial profiles were produced, but no allelic drop-out was observed. Balanced
      amplification of all loci occurred over a wide range of DNA concentrations from
      50 pg to 10 ng. Alteration of reagent concentrations and cycling parameters from
      optimal resulted in variation in the efficiency of individual locus amplification
      relative to the other loci within the system. This was also observed at high
      ionic strength or extreme pH. However, at all reagent concentrations and
      conditions, allelic drop-out was not observed. These multiplex systems have
      potential in both routine forensic and intelligence database applications.

PMID- 8874052
TI  - Comparison of different electrophoretic methods for digital typing of the MS32
      (D1S8) locus.
AB  - Minisatellite variant repeat mapping by polymerase chain reaction (MVR-PCR) is a
      new and powerful approach for individual identification from human DNA. This
      method has been successfully applied to the hypervariable human minisatellite
      MS32 (locus D1S8). In this work, we further investigate this locus using
      different electrophoretic techniques which include: agarose gels and
      nonradioactive hybridization, miniaturized polyacrylamide gels, followed by
      silver staining, and automatic detection of fluorescent labeled alleles. The
      advantages and disadvantages of each method are described. Also, MVR codes from a
      Galician population (NW Spain) are provided.

PMID- 8874053
TI  - Rapid detection of sequence polymorphisms in the human mitochondrial DNA control
      region by polymerase chain reaction and single-strand conformation analysis in
      mutation detection enhancement gels.
AB  - The article describes a rapid approach for the detection of sequence
      polymorphisms in the mitochondrial (mt)DNA control region that involves enzymatic
      amplification of each entire mtDNA control region (HV1 and HV2) and the
      subsequent analysis of the PCR products by single-strand conformation analysis
      (SSCA) in mutation detection enhancement (MDE) gels, followed by silver stain
      detection. HV1 and HV2 SSC reference ladders were developed to standardize the
      classification of the different mtDNA types. Twenty-five mtDNA types were
      observed among the 45 Spanish individuals analyzed: 11 types were observed in the
      HV1 region as compared with 10 types in the HV2 region. This mutation scanning
      strategy could be a promising method of potential use not only in forensic
      genetics but also in population and evolutionary studies.

PMID- 8874054
TI  - Genetic heterogeneity in acatalasemia.
AB  - 203 bp long products containing exon 4 and its junctions from the catalase gene
      were generated by polymerase chain reaction (PCR). These products were analyzed
      by single strand conformational polymorphism (SSCP), hetero-duplex formation and
      nucleotide sequencing. No polymorphism was detected when the Hungarian
      acatalasemic sisters, their family members and normocatalasemic controls were
      analyzed. Sequence analyses did not show the G to A point mutation at position 5
      of intron 4. This splicing mutation characterizes the Japanese-type of
      acatalasemia.

PMID- 8874055
TI  - Protein electrophoresis in polyacrylamide gels with templated pores.
AB  - An approach is described for the synthesis of nanostructured hydrogels with
      defined size channels or pores for separations of biological macromolecules.
      Polyacrylamide gels (15-20% acrylamide) were cast in the presence of high
      concentrations (5%-28%) of hydrophilic, macromolecular cosolutes either
      semirigid, rod-like polyelectrolytes (short fragments of DNA or xanthan) or
      spherical micelles of sodium dodecyl sulfate (SDS). Polyanionic cosolutes were
      then removed by a combination of diffusion and electrophoresis. These processes
      are expected to yield gels with 'templated' channels having dimensions near those
      of the double helical polymers (diameters approximately 2-3 nm, lengths of 50-200
      nm) or pores near the size of the spherical SDS micelles (approximately 4-5 nm).
      This hypothesis was tested by comparing the relative electrophoretic mobilities
      of proteins (3400 to 43,000 Da) complexed with SDS on templated and conventional
      gels. Differences in electrophoretic mobilities were observed between all
      templated gels and control normal gels, demonstrating that the templating process
      altered the polyacrylamide network. No evidence was found for phase separation of
      cosolutes from the polyacrylamide network during polymerization. Templated pores
      are expected to enhance the mobilities of molecules in a particular size range
      relative to smaller and larger molecules. Gels templated with DNA or xanthan (8
      10% final concentration) exhibited little size selectivity, but selectivity was
      observed for gels templated with SDS varied with polyacrylamide concentration in
      a manner consistent with the creation of templated pores approximately the size
      of SDS micelles and larger than the average pore size in a surrounding
      polyacrylamide network.

PMID- 8874056
TI  - Dynamics of protein isoelectric focusing in immobilized pH gradient gels.
AB  - The protein migration velocity profile through the pH gradient in immobilized pH
      gradient gels (IPG) was investigated. Strong nonuniformities of migration
      velocity distribution, which could not be remedied by adding carrier ampholytes,
      were observed at the initial stages of a run (up to several thousand volt-hour
      products for wide pH gradients). The final (after a prerun) velocity distribution
      in IPG gels differs from the one containing carrier ampholytes, with maximum
      velocity being achieved not at the pH extremes but closer to neutrality. In some
      uniform pH media, created by either a single or by several Immobilines,
      essentially a nonconstant migration profile was also obtained immediately after a
      prerun. After a prerun, followed by a pause in the absence of current, the
      phenomenon of fast evolution of the final velocity profile was found.

PMID- 8874057
TI  - Sodium dodecyl sulfate-polyacrylamide gel electrophoretic method for assessing
      the quaternary state and comparative thermostability of avidin and streptavidin.
AB  - Avidin, a positively charged egg-white protein, aggregates extensively when mixed
      at ambient temperatures with anionic detergents, such as sodium dodecyl sulfate
      (SDS). The resultant aggregates fail to penetrate the stacking gel during
      polyacrylamide gel electrophoresis (PAGE). To prevent the formation of such
      aggregates, avidin was acetylated and the pI was thus reduced. Acetylated avidin
      was found to behave in a manner similar to that of streptavidin; under
      nondenaturing conditions (i.e., incubation of samples at room temperature), both
      proteins normally migrated mainly as tetramers with a tendency to form oligomers
      of the tetramer. When samples were boiled, both proteins migrated mainly as the
      monomer. The comparative stability properties of avidin and streptavidin were
      also examined using SDS-PAGE by heating samples and determining the extent of
      dissociation of tetramers to monomers as a function of temperature. A distinctive
      transition temperature could be defined for individual samples. Using this assay,
      it was determined that, in the absence of biotin, the quaternary structure of
      streptavidin is more stable than that of avidin. Biotin appears to stabilize
      structures of both avidin and streptavidin to a similar degree. Acetylation of
      avidin thus provides a simple means to analyze the quaternary structure of the
      molecule using SDS-PAGE.

PMID- 8874058
TI  - Interpretation of electrophoretic band shapes by a partition chromatographic
      model.
AB  - Measurements of the shape of electrophoretic bands of phycoerythrin and
      conalbumin have been made at regular intervals during migration in agarose gels.
      Analysis of the peak shapes suggests the existence of a significant degree of
      asymmetry. This is to be contrasted with the symmetry around the peak associated
      with the generally assumed Gaussian band. The degree of asymmetry of the bands
      decreased as a function of time and increased with agarose concentration. A
      similar experiment on DNA indicated constancy of the degree of asymmetry as a
      function of time. These results can be interpreted as, but do not prove the
      validity of, a nonlocal diffusion equation which generalizes a theory originally
      put forth by Giddings and Eyring (J. Am. Chem. Soc. 1955, 59, 416-420). The
      results may be significant in framing a measure of the resolvability of
      electrophoretic peaks.

PMID- 8874059
TI  - Capillary sodium dodecyl sulfate-gel electrophoresis of proteins.

PMID- 8874061
TI  - Characterization of competitive binding, fluorescent drug immunoassays based on
      micellar electrokinetic capillary chromatography.
AB  - This paper characterizes competitive binding, electrokinetic capillary-based
      immunoassays for various drugs in human serum using reagents which were
      commercialized for fluorescence polarization immunoassays. After incubation of
      serum with the reactants, a small aliquot of the mixture is applied onto a fused
      silica capillary and tracers (fluorescein-labeled drugs) and the antibody-tracer
      complexes are separated and analyzed by micellar electrokinetic capillary
      chromatography with on-column laser-induced fluorescence detection. Examples
      studied include serum assays for theophylline, ethosuximide, paracetamol,
      salicylate and quinidine. With these assays, concentration-dependent peaks
      produced by the free tracers or the antibody-tracer complexes serve as the basis
      for quantitation. The sizes of the peaks produced are shown to be dependent on
      the applied power and the proportions of the reactants and serum employed. The
      separation medium permits effective characterization of tracers and antibody
      selectivities. Based on the high selectivity of the antibodies employed, the
      feasibility of the simultaneous performance of different immunoassays is
      demonstrated. For capillaries of 50 microns internal diameter (ID), separations
      are best performed at electric fields < 500 V/cm, this resulting in
      electrokinetic analyses within 4 to 10 min (capillaries of 20 to 50 cm effective
      length).

PMID- 8874060
TI  - Comparison of behavior of N-substituted acrylamides and celluloses on double
      stranded DNA separations by capillary electrophoresis at 25 degrees and 60
      degrees C.
AB  - The behavior of N-substituted poly(acrylamides) and of cellulose in the
      separation of double-stranded DNA by capillary zone electrophoresis (CZE) is
      evaluated. Contrary to previously held belief, which attributed best separations
      in poly(acrylamides) to small DNA fragments (typically in the 50-1000 bp size
      range) and in celluloses to large DNA fragments, we show that also celluloses can
      achieve fine sieving of short DNA sizes provided they are used at much higher
      concentrations than previously reported. For example, in the case of
      hydroxyethylcellulose (HEC), typically used at 0.2-0.8% concentrations, levels of
      3% produce excellent patterns, at 25 degrees C, in the 50-600 bp size range. If
      separations are conducted at 60 degrees C, sieving is lost in most liquid
      polymers. However, if the concentration of HEC is raised to 6% and that of
      hydroxypropylmethylcellulose (HPMC) above 1%, sieving is fully restored. Also, N
      substituted acrylamido derivatives, notably N-acryloylaminoethoxyethanol (AAEE)
      and N-acryloylaminopropanol (AAP) offer excellent performance at both 25 degrees
      and 60 degrees C, whereas plain poly(acrylamide) irreversibly collapses at high
      temperatures, possibly due to intrinsic instability of the amido bond under such
      harsh conditions. Among all the polymers investigated, an 8% solution of
      poly(AAP) offers the best performance and highest theoretical plates in the 25
      degree-60 degree C interval. Separations at high temperatures are necessary when
      dealing with detection of point mutations in temperature-programmed CZE and are
      preferred in DNA sequencing. Two additional advantages are evident when running
      DNA separations at 60 degrees C: a marked reduction of analysis times and a
      linearization of the transit times of the larger (434-587 bp) DNA fragments, in
      all polymers tested.

PMID- 8874062
TI  - Analysis of macromolecular branched chain polypeptides by capillary
      electrophoresis and micellar electrokinetic chromatography.
AB  - Amphoteric poly(Lys-[Glu1.0-DL-Ala4.1]), (EAK) and anionic poly(Lys-Ac-Glu0.98-DL
      Ala3.98]), (AcEAK) branched chain polypeptides were analyzed by capillary
      electrophoresis (CE) and micellar elektrokinetic chromatography (MEKC) in the
      following buffers. A1: 0.25 N triethyl ammonium phosphate (TEAP) buffer (pH
      2.25); A2: 100 mM sodium dodecyl sulfate (SDS) in buffer A1; B1: Na-borate buffer
      (pH 7.7); B2: 100 mM SDS in buffer B1; C1: Na-borate buffer (pH 11.0); C2: 100 mM
      SDS in buffer C1. Both EAK and AcEAK could be separated by a CE mechanism at pH
      2.25 and by an MEKC mechanism at pH 11.0. Optimum results were achieved with CE
      in buffer A1 and with MEKC in buffer C2.

PMID- 8874063
TI  - Some examples of the analysis of complex samples by micellar electrokinetic
      capillary chromatography with photodiode array detection.
AB  - The use of micellar electrokinetic capillary chromatography with photodiode array
      detection to assist in identifying the minor components in crude morphine, poppy
      straw and opium preparations, for the analysis of synthetic colours and other
      food additives in cordials and confectionery and for the identification of the
      ring substituted amphetamine derivative methylenedioxyethylamphetamine in illicit
      drug samples is demonstrated.

PMID- 8874064
TI  - Computer optimization of background electrolyte composition in the separation of
      metal ions by capillary electrophoresis.
AB  - The iterative regression design developed earlier for high performance liquid
      chromatography (HPLC) has been applied successfully to the optimization of the
      separation of 11 metal ions by capillary electrophoresis. The parameters used for
      optimization were pH (over the range 3.5-5.0) and the concentration of 2
      hydroxyisobutyric acid (HIBA) (2-20 mM) used as the complex-forming ligand added
      to the background electrolyte. Five initial experiments were performed and the
      response surface was calculated using the relative resolution product as
      criterion. Three additional experiments were sufficient to establish a stable
      optimum, with which all 11 metal ions were separated and well spread in the
      electropherogram. The total analysis time was less than 5 min.

PMID- 8874065
TI  - Identification of stable plant cystatin/nematode proteinase complexes using
      mildly denaturing gelatin/polyacrylamide gel electrophoresis.
AB  - The biochemical interactions between two cystatins from rice seeds, oryzacystatin
      I (OCI) and oryzacystatin II (OCII), and the cysteine proteinases from three
      plant parasitic nematodes, Meloidogyne hapla, M. incognita and M. javanica, were
      assessed using standard protease assays and mildly denaturing
      gelatin/polyacrylamide gel electrophoresis (gelatin/PAGE). Activity detected in
      extracts of preparasitic second-stage larvae (J2) from M. hapla was optimal at pH
      5.5 and was inhibited in vitro by the cysteine proteinase inhibitors trans
      epoxysuccinyl-L-leucylamido-(4-guanidino) butane, hen egg cystatin, OCI, and
      OCII. As demonstrated by class-specific activity staining, all the activity
      measured between pH 3.5 and pH 7.5 was accounted for by a major proteinase form,
      Mhp1, and two minor forms, Mhp2 and Mhp3. Mhps were also detected in extracts and
      excretions of parasitic J2 and adult females, indicating their continuous
      expression throughout development of M. hapla, and their possible involvement in
      the extracellular degradation of proteins. Interestingly, the two plant cysteine
      proteinase inhibitors OCI and OCII showed different degrees of affinity for the
      major proteinase form, Mhp1. Both inhibitors almost completely inactivated this
      proteinase in native conditions but, unlike OCII, OCI conserved a high affinity
      for Mhp1 during mildly denaturing gelatin/PAGE, showing the differential
      stabilities of the OCI/Mhp1 and OCII/Mhp1 complexes. In contrast to Mhp1, the
      major cysteine proteinases detected in the two closely related species M.
      incognita and M. javanica were strongly inhibited by OCII, while the inhibition
      of OCI was partly prevented during electrophoresis. This species-related
      efficiency of plant cystatins against nematode cysteine proteinases could have
      practical implications when planning their use to control nematodes of the genus
      Meloidogyne.

PMID- 8874066
TI  - Fish species identification by isoelectric focusing of parvalbumins in
      immobilized pH gradients.
AB  - Isoelectric focusing in immobilized pH gradients (IPG) is reported for
      unequivocal identification of fish species. Three orders of fishes have been
      analyzed: salmons, flat and cod fishes. In each family, four closely related
      species have been analyzed. For clear-cut species identification, two strategies
      have been adopted: (i) to perform IPGs in very narrow (1 pH unit and less) acidic
      gradients, typically spanning the pH 4-5 range, where fewer proteins are present
      and the pattern is much clearer; (ii) to focus the analysis on the parvalbumins,
      since this protein class if highly species-specific and resistant to heat. Thus,
      not only fresh muscle could be analyzed, but also boiled fish samples. In all
      cases unambiguous determination of each species could be performed, either by
      simple visual band inspection or, in the most difficult cases, by densitometric
      evaluation of the Coomassie-blue stained profiles. The analysis was performed in
      extracts of single species and also in mixtures of the most closely related
      species.

PMID- 8874067
TI  - The construction of the World Wide Web-accessible myocardial two-dimensional gel
      electrophoresis protein database "HEART-2DPAGE": a practical approach.
AB  - The construction of the two-dimensional electrophoresis (2-DE) gel protein
      database "HEART-2DPAGE" for human heart proteins, accessible via the World Wide
      Web (WWW), is described. This database provides the opportunity to retrieve
      descriptive information interactively by mouse clicking on a protein spot within
      a 2-DE gel image or to retrieve the position of a protein if its protein name or
      a search expression is given. The realization of searching for proteins, the
      creation of clickable spots, marked by crosses or textual information, and
      interactive viewing opportunities are discussed from a software-oriented point of
      view. The database takes into account that some human heart proteins are chamber
      specific. Several Common Gateway Interface (CGI) scripts are described and some
      practical experience is discussed.

PMID- 8874068
TI  - Amino acid analysis of proteins separated by two-dimensional electrophoresis in
      maize: isoform detection and function identification.
AB  - The possibility of using experimentally determined amino acid composition to
      assess relatedness between 75 proteins separated by two-dimensional
      electrophoresis (2-DE) and to identify them was tested on maize. Two independent
      parameters, the relative Euclidean distance and the correlation coefficient
      between the amino acid compositions, were evaluated and used. Previous sequence
      information for 31 out of the 75 proteins made it possible to evaluate the method
      for the detection of isoforms and for identification. However, the extension of
      the interrogation beyond maize to all plant sequences raised the problem of false
      positives that could nevertheless be limited by replications and by using
      additional information. The efficiency of the method to assess relatedness
      between proteins should make amino acid composition analysis a valuable tool in
      large protein characterization programs based on 2-DE, by facilitating the
      transfer of information from one well-documented organ/tissue or genotype to
      another.

PMID- 8874069
TI  - Sinusitis in mechanically ventilated patients and its role in the pathogenesis of
      nosocomial pneumonia.
AB  - Nosocomial sinusitis is a complication of endotracheal intubation and mechanical
      ventilation in critically ill patients. Its incidence is often underestimated
      because of a lack of clinical signs. It is suspected in patients with nasal
      discharge or unexplained fever. Its diagnosis is based on radiological
      examination, by radiograph or computed tomography scan, and microbiological
      cultures of maxillary sinus aspirate. Maxillary sinusitis is often associated
      with involvement of the sphenoid, ethmoid, and/or frontal sinuses. Its incidence
      varies greatly according to diagnostic criteria and the population studied.
      Infectious sinusitis is less frequent than noninfectious sinusitis, occurring in
      20 to 30% of patients intubated for at least seven days. Its incidence is higher
      in nasotracheally than in orotracheally intubated patients. Other risk factors
      include nasogastric tubes and head trauma. The main causative agents are gram
      negative bacilli, primarily Pseudomonas aeruginosa, Acinetobacter baumannii, and
      Enterobacteriaceae, but Staphylococcus aureus and yeasts are also common.
      Patients with nosocomial sinusitis are more likely to develop pneumonia than
      those without sinusitis. The sinus provides a bacterial reservoir from which
      organisms may seed the tracheobronchial tree. The association of sinusitis and
      pneumonia is mainly due to Staphylococcus aureus, Pseudomonas aeruginosa, and
      Acinetobacter baumannii. The treatment of sinusitis is based on the removal of
      all nasal tubes, topical decongestants, and maxillary sinus drainage and lavage.
      The role of intravenous antibiotics is controversial.

PMID- 8874070
TI  - Prevalence and clinical manifestations of Shiga toxin-producing Escherichia coli
      infections in Austrian children.
AB  - The prevalence and clinical manifestations of infections associated with Shiga
      toxin-producing Escherichia coli (STEC) among Austrian children were assessed.
      Stool samples from 280 pediatric patients were analyzed by enzyme immunoassay
      (EIA) for the presence of free fecal Shiga toxin (Stx) 1 and 2, and by culture on
      sorbitol MacConkey agar. Specimens testing positive by the EIA were subjected to
      a cytotoxicity assay, polymerase chain reaction analysis, and a colony
      hybridization test. Direct culture on MacConkey agar demonstrated the presence of
      three Escherichia coli O157:H7-positive stools. These were also positive by EIA
      and by the DNA-based methods. An additional six samples were positive by EIA, and
      in four of these, non-O157 STEC of serotypes O111H-, O146:H-, and O113:H53 could
      be isolated. Analysis of stools for a variety of enteric pathogens demonstrated
      that STEC was the third most common bacterial pathogen. The clinical
      manifestations of STEC infections were difficult to distinguish from those of
      infections caused by other enteric pathogens, as most patients presented with
      watery diarrhea. The median age of children with STEC infections was 27.6 months
      (range, 7 months to 5.75 years); children with Salmonella or Campylobacter
      infections were younger on average, while those with Rotavirus infections were
      older. This study demonstrated that although Escherichia coli O157:H7 could be
      identified with the same sensitivity by both EIA or agar-based methods, the
      identification of non-O157 STEC strains was enhanced by the use of EIA followed
      by colony hybridization. Analysis of overnight cultures from 53 STEC isolates
      revealed that all strains producing Stx1, Stx2, or Stx2c reacted in the EIA.
      However, culture supernatants from Stx2e-producing Escherichia coli O101 were
      negative in the EIA. Despite this disadvantage, the EIA is easy to perform and
      time efficient and can be recommended as a screening test for non-O157 STEC in
      children with diarrhea.

PMID- 8874071
TI  - Detection and identification of Mycobacterium avium in the blood of AIDS patients
      by the polymerase chain reaction.
AB  - One hundred fifty-three blood samples from patients positive for the human
      immunodeficiency virus (HIV) were analyzed by polymerase chain reaction (PCR) to
      detect the presence of Mycobacterium avium. Samples were collected from patients
      who also had blood cultures performed by a radiometric method. Blood samples were
      centrifuged on a Ficoll-Hypaque gradient to purify peripheral blood mononuclear
      cells. The purified cells were washed and incubated with a resin, boiled to
      release mycobacterial DNA, and then amplified. Polymerase chain reaction products
      were detected by a nonisotopic method. A 123 base-pair (bp) insertion sequence,
      namely IS6110, from Mycobacterium tuberculosis complex was also included in the
      reaction as an internal control of Taq polymerase activity to exclude the
      presence of enzyme inhibitors. This IS6110 fragment can be distinguished from the
      383 bp target product on ethidium bromide-stained agarose gel and may also be
      used in a colorimetric assay. Such results were compared with the results of
      culture and indicated that the assay is as sensitive as bacteriological methods,
      though faster.

PMID- 8874072
TI  - Prospective study of epidemiology and prognostic factors in community-acquired
      pneumonia.
AB  - Of 342 patients with community-acquired pneumonia, 100 were diagnosed
      etiologically. In these patients, disease epidemiology, prognostic factors, and
      influence of antibiotic treatment were analyzed prospectively. Fifty-two patients
      were treated with a broad-spectrum antibiotic (ceftriaxone), and 48 received a
      medium-spectrum antibiotic (cefuroxime); some patients in each group also
      received erythromycin. Streptococcus pneumoniae was the most frequently isolated
      microorganism (43%), followed by Chlamydia pneumoniae (21%), Haemophilus
      influenzae (19%), and Mycoplasma pneumoniae (11%). Factors significantly
      associated with increased mortality were initially critical or poor clinical
      condition, involvement of two or more lobules, and complications. Prior
      administration of antibiotics was predictive of penicillin and erythromycin
      resistance in Streptococcus pneumoniae, but had no effect on the course of the
      disease. Eight patients died, 89 were cured, and three had recurrences; there was
      no significant difference in outcome between treatment groups, regardless of
      whether patients also received erythromycin. Increased knowledge of
      epidemiological, predictive, and prognostic factors can significantly improve
      early diagnosis of community-acquired pneumonia and facilitate the choice of
      appropriate antibiotic treatment, thereby helping to reduce morbidity and
      mortality.

PMID- 8874073
TI  - Comparison of four laboratory tests for diagnosis of Clostridium difficile
      associated diarrhea.
AB  - Four different laboratory tests for diagnosis of Clostridium difficile-associated
      diarrhea were compared to determine the optimal one for management of patients
      with hospital-acquired diarrhea. Stool samples from 231 patients with diarrhea
      were tested by the following methods: culture for Clostridium difficile with
      subsequent determination of exotoxin production, with a toxigenic Clostridium
      difficile positive (TCP) result considered truly positive; enzyme immunoassay
      (EIA); latex agglutination test; and an immunobinding blot assay. The rates of
      positive results were as follows: EIA 5.5%, TCP 7.3%, latex agglutination 16.7%,
      and immunobinding blot assay 26.1%. Compared to the TCP results, the sensitivity
      and specificity were, respectively, 61 and 98% for EIA, 47 and 85% for latex
      agglutination, and 60 and 76% for the immunobinding blot assay. Samples from
      patients with > or = 6 stools/day were TCP and EIA positive in 27 and 17% of
      cases, respectively, whereas in patients with < 6 stools/day, these percentages
      decreased to 2 and 3%, respectively (p < 0.001). In hospitalized patients with >
      or = 6 stools/day, EIA appears to be the optimal test for diagnosis of
      Clostridium difficile-associated diarrhea, with a 73% positive predictive value
      and a 97% negative predictive value. However, in patients with < 6 stools/day,
      the prevalence of Clostridium difficile is low, and laboratory detection of this
      organism remains problematic.

PMID- 8874074
TI  - Comparison of disk diffusion, the E test, and detection of mecA for determination
      of methicillin resistance in coagulase-negative staphylococci.
AB  - The aim of this study was to find a reliable, fast, and simple alternative to the
      methicillin disk method for determination of methicillin resistance in coagulase
      negative staphylococci, since results of this method are often difficult to read
      due to growth within the zone of inhibition. The sensitivity of 319 strains of
      coagulase-negative staphylococci to a 5 microgram methicillin disk on Mueller
      Hinton agar using an incubation period of 48 h was compared with that of 1
      microgram and 5 micrograms oxacillin disks on Mueller-Hinton agar with or without
      2% NaCl, using an incubation period of 24 h. The detection of mecA (MecAgen) by
      the polymerase chain reaction was used as a standard. Minimum inhibitory
      concentrations were determined by means of the E test. Of the 225 mecA-positive
      strains, 190, 215, and 193 were resistant to 5 micrograms methicillin, 1
      microgram oxacillin and 5 micrograms oxacillin disks on Mueller-Hinton agar,
      respectively, and 216, 218, and 223 were resistant on Mueller-Hinton agar with 2%
      NaCl. Of the 94 mecA-negative strains, 89, 93, and 94 were susceptible to 5
      micrograms methicillin, 1 microgram oxacillin, and 5 micrograms oxacillin disks
      on Mueller-Hinton agar, respectively, and 92, 93, and 94 were susceptible on
      Mueller-Hinton agar with 2% NaCl. Using breakpoints of 2 micrograms/ml for
      oxacillin resistance and 8 micrograms/ml for methicillin resistance, the E test
      yielded sensitivities of 99.6 and 99.1% and specificities of 97.9 and 98.9% after
      48 h of incubation. The 5 microgram oxacillin disk was faster and easier to read
      than the methicillin disk and correlated better with detection of mecA than the
      methicillin disk of the 1 microgram oxacillin disk.

PMID- 8874075
TI  - Patterns of resistance and sensitivity to antiviral compounds of drug-resistant
      strains of human cytomegalovirus selected in vitro.
AB  - Drug-resistant human cytomegalovirus (HCMV) strains were selected in human
      embryonic lung (HEL) fibroblasts under pressure of the (S)-3-hydroxy-2
      phosphonylmethoxypropyl (HPMP) derivatives of cytosine (HPMPC) and adenine
      (HPMPA), the 2-phosphonylmethoxyethyl (PME) derivative of 2,6-diaminopurine
      (PMEDAP), ganciclovir (GCV), acyclovir (ACV), and foscarnet (PFA). Drug
      susceptibility profiles of the different drug-resistant (i.e., GCVr, HPMPCr,
      HPMPAr, PFAr, ACVr, and PMEDAPr) strains were determined in HEL cells. A
      considerable degree of cross-resistance against GCV, HPMPC, and HPMPA occurred
      with GCVr, HPMPCr, and HPMPAr strains. No changes in susceptibility to 9-(2
      phosphonylmethoxyethyl)adenine (PMEA), PMEDAP, ACV, or PFA were detected for the
      HPMPCr, HPMPAr, and GCVr strains when compared to the wild-type virus. On the
      other hand, a significant degree of cross-resistance was noted with the PMEDAPr,
      PFAr, and ACVr strains against PMEA, PMEDAP, PFA, and ACV. NO differences in
      susceptibility to HPMPC, HPMPA and GCV were observed for the ACVr, PFAr, and
      PMEDAPr strains relative to the wild type. The drug susceptibility profiles of
      the different resistant strains point to a common mechanism of HCMV resistance to
      PFA and the PME derivatives that is different from the mechanism of HCMV
      resistance to the HPMP derivatives.

PMID- 8874076
TI  - Results of a double-blind placebo-controlled study of the double-stranded RNA
      drug polyI:polyC12U in the treatment of HIV infection.
AB  - In this multicenter, randomized, double-blind study the activity of
      polyI:polyC12U administered with zidovudine was evaluated in the treatment of HIV
      infection. Thirty-six HIV-positive, pre-AIDS individuals (100-500 CD4+ cells/mm3)
      who had had at least six months of zidovudine therapy received polyI:polyC12U
      (400 or 700 mg) or placebo twice weekly with zidovudine. PolyI:polyC12U subjects
      with baseline CD4+ counts > or = 300/mm3 showed a trend towards reduced CD4+ loss
      versus placebo recipients. PolyI:polyC12U subjects were more likely to exhibit
      positive delayed-type hypersensitivity responses than placebo recipients. Placebo
      subjects crossing over to polyI:polyC12U therapy demonstrated improved CD4+ and
      delayed-type hypersensitivity responses. PolyI:polyC12U subjects with baseline
      CD4+ counts > or = 300/mm3 were less likely to develop AIDS than similar placebo
      subjects. PolyI:polyC12U therapy of HIV-positive subjects restored or stabilized
      immune function as indexed by delayed-type hypersensitivity reactivity and, in
      individuals with CD4+ counts > 300/mm3, abrogated CD4+ loss and reduced disease
      progression. PolyI:polyC12U was generally well-tolerated in this zidovudine
      treated population. No subject discontinued therapy due to an adverse reaction or
      aberrant laboratory parameter.

PMID- 8874077
TI  - Serologic responses to Rhodococcus equi in individuals with and without human
      immunodeficiency virus infection.
AB  - Thirty healthy blood donors, 15 workers from horse-breeding farms, 69 human
      immunodeficiency virus (HIV)-negative persons at risk for HIV infection, 125 HIV
      infected subjects without Rhodococcus equi infection, and nine HIV-infected
      patients with Rhodococcus equi pneumonia were evaluated in order to detect serum
      antibodies to Rhodococcus equi precipitate-soluble antigen by an enzyme
      immunoassay (EIA). Whereas EIA values for healthy donors, horse farm workers,
      individuals at risk for HIV infection, and HIV-positive subjects without
      Rhodococcus equi infection were comparable, HIV-infected patients with
      rhodococcal disease had significantly higher Rhodococcus equi antibody levels (p
      < 0.0001). The clinical outcome of Rhodococcus equi pneumonia was more severe in
      subjects who had low levels of specific antibodies, whereas patients who
      recovered had elevated Rhodococcus equi antibody levels over time. Immunoblot
      studies showed that both Rhodococcus equi-infected patients and foals recognized
      a protein band of approximately 60 kDa in the Rhodococcus equi precipitate
      soluble antigen. On the other hand, the Rhodococcus equi-infected patients did
      not react with the diffuse 15 to 17 kDa virulence-associated proteins that
      represent important virulence factors both in mice and horses.

PMID- 8874078
TI  - Polymerase chain reaction versus culture for detection of Ureaplasma urealyticum
      and Mycoplasma hominis in the urogenital tract of adults and the respiratory
      tract of newborns.
AB  - The efficiency of the polymerase chain reaction (PCR) was compared with that of
      culture for detection of Ureaplasma urealyticum and Mycoplasma hominis in 726
      clinical specimens comprising 189 gynecological samples, 362 urological samples,
      and 175 samples from newborn infants. The sensitivity of PCR versus culture was
      95% for both organisms, while the sensitivity of culture versus PCR was 91% for
      Ureaplasma urealyticum and 84% for Mycoplasma hominis. Furthermore, PCR tests
      were faster than culture tests, allowing the time to diagnosis to be reduced from
      two to five days to 24 h.

PMID- 8874079
TI  - Nonsurgical cure of isolated cerebral mucormycosis in an intravenous drug user.
AB  - The case of a 30-year-old, female, HIV-positive intravenous drug user who
      suffered from isolated cerebral mucormycosis is reported. Treatment with
      amphotericin B at an accumulative dose of 5.5 grams led to significant recovery,
      and there was no recurrence of disease over a follow-up period of six months.
      Patients with isolated cerebral mucormycosis in whom surgery would be a high-risk
      or impossible procedure could be managed medically with prolonged courses of
      intravenous amphotericin B.

PMID- 8874080
TI  - Scedosporium apiospermum pneumonia after autologous bone marrow transplantation.
AB  - Although opportunistic infections after bone marrow transplantation (BMT) are
      very common, only five cases of Pseudallescheria boydii infection have been
      reported in the literature, two of which were autopsy findings. A case of
      Scedosporium apiospermum infection after BMT, treated initially with amphotericin
      B (total dose of 2.5 g) and then with itraconazole (for 25 days), is reported
      here. When the patient failed to improve, Scedosporium apiospermum pneumonia was
      diagnosed and therapy was changed. The patient was treated successfully with
      miconazole (600 mg/8h for 32 days) and ketoconazole (200 mg/8h for 7 days) plus
      surgery.

PMID- 8874081
TI  - Specific and sensitive two-step polymerase chain reaction assay for the detection
      of Salmonella species.
AB  - A polymerase chain reaction (PCR) assay was applied for the selective
      amplification of a characteristic sequence within a Salmonella-specific
      chromosomal fragment. A two-temperature PCR cycle enhanced both the speed and
      overall sensitivity of the amplification procedure. Twenty-one well-characterized
      Salmonella strains and a number of non-Salmonella strains were tested. With the
      exception of the rarely isolated Salmonella arizonae strain, the PCR-based
      approach enabled the specific identification of Salmonella with a detection limit
      of 10(3) organisms. In combination with a nested PCR assay, as few as ten
      organisms were detectable. Specificity was demonstrated as no distinct
      amplification products were detectable with any of the tested non-Salmonella
      strains. With a pre-enrichment step using paramagnetic anti-Salmonella beads, an
      increase in sensitivity was observed in the case of clinical samples while the
      amplification process was not influenced.

PMID- 8874082
TI  - A new selective differential medium for isolation of Stenotrophomonas
      maltophilia.
AB  - A new selective differential medium for the isolation of Stenotrophomonas
      (formerly Xanthomonas) maltophilia was developed. The medium, VIA agar, contained
      vancomycin, imipenem, and amphotericin B as selective agents and incorporated a
      mannitol/bromothymol blue indicator system. Compared with Xanthomonas maltophilia
      Selective Medium (XMSM), VIA agar was less inhibitory to Stenotrophomonas
      maltophilia and was more selective than XMSM in preventing the growth of unwanted
      bacteria from contaminated specimens. Although vancomycin-resistant strains of
      Enterococcus faecium may grow on VIA agar, these can be easily distinguished from
      Stenotrophomonas maltophilia because of mannitol fermentation.

PMID- 8874083
TI  - Bacteremia due to glucose non-fermenting gram-negative bacilli in patients with
      hematological neoplasias and solid tumors.
AB  - Twenty-six patients with hematological or solid tumors who developed bacteremia
      caused by Stenotrophomonas maltophilia (n = 10), Pseudomonas putida (n = 6),
      Sphingomonas paucimobilis complex (n = 4) or Alcaligenes xylosoxidans (n = 6) in
      the period between 1993 and 1995 were studied. Seventeen patients were
      neutropenic during the infection, and 13 were undergoing bone marrow or
      peripheral blood stem cell transplantation. Twenty-three patients had catheter
      related infections; only 3 of the 26 patients developed septic complications (all
      due to Stenotrophomonas maltophilia). Twenty patients were cured following
      catheter removal, either as primary measure (n = 8) or salvage measure (n = 12).
      Four responded to antibiotic therapy only, and two died of septic complications.
      Such infections in hematological and oncological patients have increased in this
      hospital from no cases in 1975 to 11 cases in 1995.

PMID- 8874084
TI  - Absence of spontaneous autolysis of Streptococcus pneumoniae in aerobic fan
      culture bottles in a commercial blood culture system.

PMID- 8874085
TI  - Sepsis due to multiply resistant Corynebacterium amycolatum.

PMID- 8874086
TI  - Niels Stensen (Niccolo Stenone) and his first scientific offspring: the salivary
      glands.
AB  - Niels Stensen's (Niccolo Stenone) life and scientific achievements are briefly
      outlined and discussed. Particular attention is focused on his contribution to
      the understanding of salivary and exocrine secretions.

PMID- 8874087
TI  - Contemporary approaches to the study of salivary gland morphogenesis.
AB  - The submandibular gland of the mouse and rat serves as an important model to
      study epitheliomesenchymal interactions, since it can be studied both in vivo and
      in vitro. Previous work has established that the extracellular matrix, and
      especially the basal lamina, play vital roles in the development of this gland.
      More recent studies have indicated that integrins and several oncogene-related
      products, including components of the epidermal growth factor system, also play
      important roles in this gland's development.

PMID- 8874088
TI  - Immunocytochemical studies of cell differentiation during rat salivary gland
      development.
AB  - The development of the rat submandibular and parotid glands has been studied
      using antibodies to secretory proteins as cell-specific markers. Although the
      morphology of the glands and the timing of the main steps of cytodifferentiation
      are substantially different, they have several proteins and developmental
      features in common. The latter include the initial formation of perinatal acini
      which undergo a transition to adult acini expressing a different complement of
      secretory proteins; the development of adult intercalated ducts (ID) from the
      perinatal acinar cells; and the retention of the perinatal phenotype in some
      cells of the ID.

PMID- 8874089
TI  - Salivary glands, cellular evolution, and adaptive radiation in mammals.
AB  - Evolutionary theory provides the foundation for interpretation of the natural
      world, but one remaining major challenge is to link genetic variation and
      particular gene products to natural selection and adaptation. Another challenge
      is to describe the role of cells, especially secretory cells, in the evolutionary
      process. Comparative studies of mammalian salivary glands could serve as an
      insightful model. Our theoretical approach combines data on genomic and
      chromosomal evolution with data on secretory cells and proteins so that
      adaptation can be understood in context of these interrelated components. The
      present paper reviews patterns and types of interspecific salivary gland cell
      variation that we have documented at the ultrastructural level. This data set
      shows ways in which secretory cells and the secretory process may have been
      evolutionarily modified in mammals. As a further example of our approach we also
      review how proline-rich-proteins (PRPs) may have had adaptive significance in the
      evolution of mammals, especially rodents. Our working hypotheses are: that Ca+2
      binding acidic PRPs are incompatible with ever-growing dentition; and that
      presence or absence of tannin-binding basic PRPs was a major factor in ecological
      diversification in rodents. Some rodents might even exhibit behavioral
      compensation for absence of basic PRPs in their saliva and this illustrates the
      complex alternatives available to natural selection.

PMID- 8874090
TI  - Histological convergent evolution of the accessory submandibular glands in four
      species of frog-eating bats.
AB  - The accessory submandibular glands in four species of bats were examined by
      electron microscopy. These four species represent two independently evolved
      lineages. The fringe-lipped bat, Trachops cirrhosis, is a Neotropical
      phyllostomid species, whereas the false vampire bats of southeast Asia, Megaderma
      lyra and M. spasma, and the heart-nosed bat, Cardioderma cor, of East Africa are
      megadermatid species. These glands show extreme deviation from typical salivary
      gland histology: their secretory endpieces are in the form of follicles and their
      ducts lack the cytological details that permit identification of diverse duct
      segments. Despite their unusual histology, the secretory endpieces in M. lyra, M.
      spasma, and C. cor consist of secretory cells that conform to typical secretory
      cell morphology. In contrast, secretion by follicular cells in T. cirrhosis
      involves unusual cytoplasmic bodies, and their mitochondria frequently have
      intracristal crystalloids. Ducts in all four species consist of simple cuboidal
      to columnar epithelium without basal striations. Follicles and ducts in all four
      bats are surrounded by numerous myoepithelial cells and are heavily innervated by
      hypolemmal nerve terminals. Despite their widely separated geographical ranges,
      all four bat species consume frogs and other vertebrates. Frogs and toads often
      possess toxic cutaneous glands that provide a chemical defense against predation.
      It is postulated that the unusual accessory glands in the four frog-eating
      species secrete toxin-neutralizing salivary factors. The follicular form of the
      endpieces permits storage of preformed saliva and their coterie of myoepithelial
      cells and hypolemmal nerve terminals facilitates the sudden and rapid expulsion
      of saliva into the oral cavity during the consumption of noxious amphibians.

PMID- 8874091
TI  - Season related ultrastructural features of the parotid, submandibular and von
      Ebner's glands in hibernating bats.
AB  - The parotid, submandibular and the von Ebner's salivary glands of hibernating
      insectivorous bats (Pipistrellus pipistrellus, Rhinolophus f. e. and Eptesicus
      serotinus) were studied by transmission electron microscopy and by histochemical
      methods during various seasons of the year. We report the seasonal
      ultrastructural changes that occur in the cytoplasmic organelles and the
      secretory granules of the serous and mucous cells and in the intercalated and
      striated ducts of the major glands. It previously has been hypothesized that the
      heterogeneity of the inclusions in the serous granules is closely related to the
      varying seasonal levels of proteinaceous and glycidic constituents. Lymphatic
      vessels are present only in the perivascular and periductal connective tissue.
      Morphofunctional and comparative studies seem to confirm a relationship between
      secretory activity and nutritional status as well as a likely involvement of the
      intercalated and striated ducts in determining the composition of the saliva.

PMID- 8874092
TI  - Glycosylation of secretory proteins in salivary glands and saliva studied by
      lectin-probes.
AB  - Lectin-probes were used histochemically to study glycosylation patterns in
      prepackaged secretory material in cat and rat submandibular glands and to assess
      the secretory changes induced by nerve stimulations. The same probes were also
      used for correlative biochemical assessments of the constituents in glandular
      extracts and in saliva from the same experiments, after electrophoretic
      separations and immobilization on nitrocellulose membranes. These studies
      provided a broader understanding than the use of either procedure alone. Lectin
      binding patterns in saliva were more complex than anticipated from the
      histochemistry and this probably relates to the presence of different
      constituents in secretory granules and a greater availability of binding sites
      biochemically. In cats, parasympathetic stimulation caused depletion of lectin
      staining in acini and to some extent in demilunes, whereas sympathetic
      stimulation caused depletion of lectin binding in striated ducts and reduction in
      demilunar size. Biochemically after SDS-PAGE of saliva similar secretory effects
      were observed but each nerve also evoked some secretion from the cells not
      showing histochemical change. In rats, sympathetic stimulation caused depletion
      of lectin positive granules from both acini and granular tubules. After SDS-PAGE
      of the saliva one zone of lectin binding 94-150 kD (Mr) was identified as acinar
      mucin. Granular tubule proteins consisting mainly of kallikreins occurred in a
      zone 25-35 kD (Mr) and lectin bindings suggested that different kallikreins may
      be differently glycosylated. This unexpected possibility was confirmed on slot
      blot preparations of separated kallikreins, which also revealed the novel finding
      that some kallikreins are O- as well as N-glycosylated.

PMID- 8874093
TI  - Sialylation patterns of the mouse parotid secretory granules. Combined
      deacetylation, enzymatic degradation and lectin-gold binding.
AB  - We investigated the lectin cytochemistry of control and sialidase-digested
      sections of the mouse parotid gland by postembedding techniques. PNA and DBA
      lectins were used and their affinity sites were localized by employing conjugates
      with horseradish peroxidase that then reacted with anti-horseradish peroxidase
      antibody and protein A-gold. Potassium hydroxide pretreatment also was used
      before sialidase/PNA and DBA binding to investigate sialic acid acetylation.
      Ultrathin sections were obtained from specimens embedded in the acrylic
      hydrophilic resin, Bioacryl. The acini of mouse parotid gland contained
      polymorphous secretory granules differentially stained by the two lectins; the
      use of sialidase digestion and KOH deacetylation revealed that the sialic acids
      linked to beta-galactose are restricted to the electron-dense concentric areas of
      target granules, whereas the sialic acids linked to alpha-N-acetylgalactosamine
      contain C4-acetylated groups and are preferentially located in the electron
      lucent regions of bizonal granules.

PMID- 8874094
TI  - Salivary glands, glycoconjugates and diabetes mellitus.
AB  - It is generally accepted that glycoconjugates secreted by salivary glands are
      important in the protection of the oral environment. Studies with diabetic
      rodents have shown that their salivary glands are adversely affected. Little
      effort has been made to determine whether altered synthesis and/or secretion of
      glycoconjugates occur in salivary glands of diabetic individuals, either human or
      non-human. The major salivary glands of male Swiss-Webster mice, rendered
      diabetic with alloxan, were examined and compared to controls. Sections of major
      salivary glands were examined using a battery of non-lectin staining methods for
      glycoconjugates. Granular duct diameters were measured in sections of the
      submandibular glands (SM) from controls and all experimental groups. Neutral
      glycoconjugate staining in SM acini of glands from diabetic animals was
      depressed, while staining of acidic glycoconjugates increased. Neutral
      glycoconjugate staining in granular ducts of SM glands of diabetic animals was
      depressed, as were granule content and granular duct diameters. Induced diabetes
      did not affect staining of neutral glycoconjugates in parotid glands but staining
      of acidic non-sulfated glycoconjugates appeared to increase. There were no
      apparent differences in neutral or acidic glycoconjugate staining of sublingual
      (SL) glands of diabetic or control mice.

PMID- 8874095
TI  - Ultrastructural localization of blood group antigens in human salivary glands.
AB  - The subcellular distribution of several blood group antigens was studied in human
      major and minor salivary glands by means of a postembedding immunogold staining
      method. In each gland, antigens were detected as secretory products and as cell
      surface components. A, B, H and Lewis (a,b,x,y) antigens were found in mucous
      cells depending on the ABO and secretor status; reactivities were confined to the
      secretory granules. In serous and ductal cells, both the secretory granules and
      cell membranes were reactive, but only for H, Le-b and Le-y irrespective of the
      ABO and secretor status.

PMID- 8874096
TI  - Connexin expression in the salivary glands.
AB  - To investigate the ultrastructure of gap junctions and functional differences
      between connexin (gap junction structural protein) 32 and 43 in the rat
      submandibular and sublingual glands, tracer and freeze-fracture methods were
      carried out, and the expression of both connexins was examined. In both glands,
      western blot analysis with anti-connexin 32 and 43 antibodies revealed bands of
      about 27kD and 43kD, respectively. Immunofluorescence showed the presence of
      connexin32-positive spots between acinar cells in both glands. In contrast,
      connexin43-positive spots were observed at the periphery of the acinar structures
      in either gland. Positive spots for both connexins could not be detected between
      ductal cells in both glands. By immunocytochemistry, connexin32 was found on the
      gap junctional membranes of acinar cells and connexin43 on the gap junctional
      membranes of myoepithelial cells. It is surmised that connexin32 of the gap
      junction is related to the secretory function of acinar cells and that connexin43
      is associated with the contraction of the myoepithelial cells.

PMID- 8874097
TI  - X-ray microanalysis applied to the study of salivary glands.
AB  - X-ray microanalysis can be used to study the distribution of elements in salivary
      glands at the cellular and subcellular level in a variety of physiological and
      pathophysiological conditions. The acinar cells of the adult rat and mouse
      submandibular gland contain high concentrations of calcium due to the presence of
      calcium-rich secretory granules. The calcium concentration of the acinar cells
      can be increased under a variety of pathophysiological conditions, e.g., in
      animal models for cystic fibrosis, due to an increase in the number of secretory
      granules and changes in their calcium-binding properties. Cholinergic stimulation
      results in a decrease in the concentrations of Cl and K in all cell compartments
      in adult animals, but not in newborn rats. Also the secretory granules in the
      glands in adult animals lose Cl and K, indicating that ion (and water) transport
      mechanisms may be present in the membrane of the granules. During chemical
      fixation, the secretory granules in the adult glands swell and their morphology
      is different from that in freeze-substituted glands. The characteristics of the
      secretory granules in the acinar cells of newborn rats are different from those
      of adult animals.

PMID- 8874098
TI  - Further data on intracellular structures of human salivary glands. A SEM study.
AB  - Specimens of human salivary glands have been studied by our modification of the
      AODO maceration method which, carried out on sections of controlled thickness,
      allows the analytical study of human bioptical material. Lately, our technique
      has been further improved and simplified by omitting the treatment with
      dimethylsulfoxide and by using osmium-ferrocyanide as secondary fixative.
      Following maceration with diluted OsO4, some of the sections also were shaken for
      10-15 min with a rotating agitator. Already at low magnification, all parenchymal
      cells were clearly distinguishable for their complement of cytoplasmic
      organelles. Serous cells and mucous cells at the beginning of their secretory
      cycle were characterized by well developed RER and Golgi apparatus, while mature
      mucous cells exhibited only scanty organelles compressed among the secretory
      droplets. Mitochondria were tubular, and often branched and convoluted. When
      sectioned, these organelles, besides the usual plate-like cristae, showed tubular
      cristae as well. The SER of striated and excretory duct cells was well developed
      and consisted of a network of smooth anastomosing tubules in the apical cytoplasm
      where it probably represented the transcellular pathway for ion transport. In
      specimens subjected to shaking, cytoplasmic organelles were occasionally removed
      allowing a nonobstructed view of the inner side of the plasmalemma and its
      specializations. With this technique the intercellular canaliculi of serous cells
      also became appreciable from their cytoplasmic side. They appeared as ribbon-like
      irregular protrusions with walls fenestrated by holes, corresponding to the
      interior of microvilli deprived of the cytoskeleton, and, sometimes, with lateral
      expansions possibly related to the mechanism of exocytosis. Results reported here
      clearly showed the usefulness of the maceration method in providing additional
      data on the cytoarchitecture of epithelial cells of salivary glands. Furthermore,
      by allowing the visualization of internal surfaces previously hidden to direct
      inspection, our technique may open new horizons in morpho/functional studies of
      human salivary glands.

PMID- 8874099
TI  - Dynamics of salivary secretion studied by confocal laser and scanning electron
      microscopy.
AB  - Plasma membrane events during secretion of the parotid and submandibular glands
      of humans and rats were observed in living cells by confocal microscopy and from
      the cytoplasmic side by scanning electron microscopy after removal of the cell
      organelles by the OsO4 maceration method. These new microscopic techniques
      revealed in acinar cells two distinct exocytosis-endocytosis coupling mechanisms
      elicited in response to different secretory stimuli. Beta-adrenergic stimulation
      with isoproterenol and its second messenger analog dibutyryl cyclic AMP evoked
      exocytosis after which fused granule membranes were individually removed from the
      luminal plasma membrane within several minutes. On the fused membrane area, small
      endocytotic vesicles about 100-150 nm in diameter were abundant. Muscarinic
      stimulation with carbachol also induced exocytosis, but in this case the fused
      granule membranes coalesced to form enlarged invaginations which stayed on the
      luminal membrane for more than 30 min. These invaginations, almost devoid of
      small endocytotic vesicles, were then pinched off from the luminal membrane and
      dispersed into the cytoplasm in the form of light microscopically detectable
      vesicles. After treatment with isoproterenol and carbachol, acinar cells
      exhibited different distributional changes of F-actin around the fused membrane
      area, suggesting the involvement of microfilaments in regulating the membrane
      events following exocytosis.

PMID- 8874100
TI  - The rodent granular convoluted tubule cell--an update.
AB  - The cells of the granular convoluted tubule (GCT) of the rodent submandibular
      gland (SMG) are under complex developmental and multihormonal regulation. Recent
      findings indicate that GCT cells also synthesize transforming growth factor alpha
      (TGF-alpha), hepatocyte growth factor, erythroid differentiation factor,
      endothelin, and insulin-like growth factor, as well as several novel androgen
      dependent proteins of unknown function. The GCTs of hypophysectomized mice
      provide a convenient model to study multihormonal regulation of gene expression.
      The GCT system of the rodent SMG also is a fruitful model for study of hormone
      receptors.

PMID- 8874101
TI  - Tuft cells in the main excretory duct epithelia of the three major rat salivary
      glands.
AB  - We report the tuft cells in the main excretory duct epithelia of rat salivary
      glands. These cells exhibit similar fundamental characteristics in the salivary
      glands and in other organs. However, numerous membrane-bound electron-dense
      granules are present among the microvilli of the tuft cells in the submandibular
      gland, but not in other organs. The apical cytoplasm contains numerous vesicles
      with a filamentous substance that reacts positively for glycoconjugates. The
      vesicles frequently are close to the apical plasma membrane and seem to open into
      the lumen. Nerve endings with synaptic vesicles are seen close to the basal
      portion of the tuft cells. The ratio of the tuft cells to principal cells is
      highest in the submandibular gland and lowest in the sublingual gland. The
      functions of the tuft cells in the salivary glands are suggested to be secretion,
      absorption, and reception.

PMID- 8874102
TI  - The significance of lamellated structure of Golgi apparatus in parotid acinar
      cells.
AB  - By reviewing briefly our recent study, the functional significance of lamellated
      structure of the Golgi apparatus (GA) was discussed. We have examined the
      structural alterations and distribution of Golgi related proteins in GA
      disorganized by brefeldin A (BFA), okadaic acid (OA), monensin and nocodazole
      (NOC) by means of electron microscopy. BFA and OA induced rapid disruption of
      lamellated structure of GA into groups of small vesicles and tubules. The effect
      of these drugs was reversible, and lamellated structure recovered immediately
      after withdrawal of the drugs. Immunoelectron microscopy revealed that the
      localization of amylase, GF-1 antigen (a resident protein of trans membrane of
      GA) and cathepsin D was modified considerably in the cells whose lamellated
      structures were in the middle of disorganization or reconstruction. These
      modifications include appearance of cathepsin D and GF-1 immunoreactivity in the
      secretory granules. Furthermore, there was evidence that secretory products were
      discharged not only into the acinar lumen but also into the baso-lateral spaces.
      In contrast, the stacked configuration was preserved in GA after treatment with
      monensin or NOC. Localization of immunoreactivity of the Golgi related proteins
      was essentially not changed by these drugs. These findings suggested that the
      cisternal stack of GA was the structural background for the normal sorting of
      secretory proteins.

PMID- 8874103
TI  - Secretory granule formation and synthesis pathway of secretory proteins in
      parotid gland cells.
AB  - The cytochemical technique for endogenous peroxidase and an immunocytochemical
      method with protein A-gold were used to investigate the formation of the
      secretory granule substructure in acinar cells of the gerbil parotid glands in
      normal conditions and after treatment with the ionophore monensin. In untreated
      animals and 90 min after treatment with monensin, peroxidase activity was seen in
      rER, in transport vesicles close to the condensing vacuoles, and in the dense
      core of condensing vacuoles and secretory granules, whereas the Golgi cisternae
      remain unreactive. At 45 or 60 min after stimulation with monensin, the
      condensing vacuoles and the immature granules in the trans Golgi area did not
      exhibit dense cores and their content appeared similar to the peripheral portion
      of the mature secretory granules. These observations suggest that, in Mongolian
      gerbil parotid acinar cells, some substances such as peroxidase may be
      transported from the rER directly to the condensing vacuoles.

PMID- 8874104
TI  - Von Willebrand disease.

PMID- 8874105
TI  - Helicobacter pylori disease in childhood.

PMID- 8874106
TI  - Tribological and mycological consequences of the use of a miconazole nitrate
      containing paste for the prevention of diaper dermatitis: an open pilot study.
AB  - The diaper environment increases the coefficient of skin friction and compromises
      the function of the stratum corneum. In this study, the tribological and
      mycological benefit of the use of a miconazole nitrate-containing paste on
      diapered skin was evaluated. A total of 135 instrumental measurements of both
      erythema and stratum corneum alterations were made on alternate days for 3 weeks
      in 15 infants. Biometrological parameters were the chromacity a* of the skin and
      the squamometry index. Cultures testing for Candida albicans were also performed.
      In the days following the use of the paste, the chromacity a*, the squamometry
      index and the number of positive cultures of C. albicans were significantly
      reduced compared to the same evaluations made off treatment. CONCLUSION:
      Miconazole nitrate-containing paste reduces the tribological interference between
      cloth diapers and skin as well as providing the diapered skin with an improved
      microbial environment.

PMID- 8874107
TI  - Familial pyoderma gangrenosum presenting in infancy.
AB  - Pyoderma gangrenosum (PG) is a rare, poorly understood skin disease that occurs
      in all age groups. Less than 0.4% of patients are infants and represent a
      diagnostic challenge as early lesions may resemble other skin disorders. Here we
      report for the first time three siblings affected with PG all presenting during
      infancy. Unlike the older age group, the ulcers spared the legs but involved the
      buttocks, thighs and perianal area in all the infants. CONCLUSION: This is the
      first reported family with PG affecting three siblings suggesting autosomal
      recessive inheritance. The diagnosis may be more difficult in infants due to
      absence of underlying associated disorders and the tendency of the lesions to
      appear in areas where infants frequently have other dermatoses. PG
      characteristically involves the buttocks, thighs and perianal area and spares the
      legs.

PMID- 8874108
TI  - Gonadal function of young adults after therapy of malignancies during childhood
      or adolescence.
AB  - As the survival rate of children with malignancies has increased over past
      decades, the follow up of adult long-term survivors (LTS) of childhood cancer
      should focus on late effects of disease and treatment. Gonadal function was
      therefore studied in 54 LTS (aged 17-29 years; 33 male, 21 female) 2-18 years
      after treatment for malignancies during childhood or adolescence. To analyse the
      sensitivity of different diagnostic methods, tests of endocrine function (n =
      52), spermiograms (n = 14), gynaecological status (n = 20) and ultrasonography of
      the gonads (n = 53) were compared with the results of equivalent tests in 23 age
      matched normal controls (12 male, 11 female). There were no differences between
      male and female LTS concerning age at diagnosis, gonadal dose of irradiation
      (XRT) and doses of applied chemotherapeutic agents. Whereas male LTS had elevated
      levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) before
      (P < 0.05; P < 0.001) and after (P < 0.01; P < 0.001) stimulation with
      gonadotropin releasing hormone, female LTS exhibited normal endocrine function.
      Accordingly, male patients exhibited lower testicular volumes than normal
      controls, as measured with a Prader orchidometer (P < 0.01) or by ultrasonography
      (P < 0.001). Gynaecological status and ultrasonography of the gonads were normal
      in female LTS and controls. Whereas all spermiograms of normal controls (n = 8)
      showed a normal sperm cell density (SCD), only 2 of 14 male LTS exhibited a
      normal SCD (P < 0.001). Azoospermic LTS (n = 9) had been treated more often with
      alkylating agents and had received higher (P < 0.05) gonadal doses of XRT. All
      male LTS with testicular volumes below the normal range (< 13 ml) and basal FSH
      levels above the normal range (> 10 IU/l) exhibited azoospermia, whereas LTS with
      normal values for testicular volume and basal FSH had a normal SCD. CONCLUSION: A
      sex-specific susceptibility for gonadal damage after treatment for malignancies
      might be responsible, in part, for the impaired gonadal function of male LTS.
      Therapy with alkylating agents and/or high gonadal doses of XRT were important
      risk factors for azoospermia. A simple method to estimate potential fertility in
      individual LTS is to measure testicular volume, using a Prader orchidometer, and
      basal FSH serum levels.

PMID- 8874109
TI  - Prospective study of the atopy preventive effect of maternal avoidance of milk
      and eggs during pregnancy and lactation.
AB  - The preventive effect of maternal avoidance of cow's milk and eggs on the
      development of atopic dermatitis and sensitization to food allergens was studied
      in a prospective trial with families at high risk for atopy, intervention
      included encouraging exclusive breast feeding for at least 3 months and delaying
      the controlled introduction of solid foods. In addition, one group received a
      maternal diet with the complete avoidance of milk and eggs in the last trimester
      of pregnancy and during the period of exclusive breast feeding, another group had
      the same diet starting after delivery, and mothers of the third group had no
      dietary restrictions. The period prevalences of atopic dermatitis as well as the
      rates of specific sensitization to eggs and milk at 6 and 12 months were not
      significantly different between groups. We were unable to demonstrate a
      significant preventive effect of maternal diet. CONCLUSION: While breast feeding
      should be promoted for children at risk for atopy, mothers can be encouraged to
      stay on normal diet during pregnancy and the breast feeding period.

PMID- 8874110
TI  - Severe tick-borne encephalitis following passive immunization.
AB  - We report on a 5-year-old girl with an unusually severe course of tick-borne
      encephalitis following passive immunization with specific hyperimmune globulin
      after a tick bite in an endemic area. Serial investigations of the CSF revealed
      intrathecal production of specific antibodies paralleled by increasing numbers of
      B-cells after initial T-cell pleocytosis. Focal central lesions were evident on
      MRI. CONCLUSION: The severity of the presented case questions the benefit of
      passive immunization and rather justifies consideration of vaccine recommendation
      to residents and travellers to areas endemic for tick-borne encephalitis virus.

PMID- 8874111
TI  - The frequency of resistance to erythromycin in group A streptococci in Ankara.
AB  - The frequency of resistance to erythromycin of group A beta-haemolytic
      streptococci in the last 7 years was determined in three medical centres in
      Ankara. While all group A beta-haemolytic streptococci strains were susceptible
      to penicillin, a gradual increase in resistance to erythromycin until 1992 was
      observed. However, a substantial increase in erythromycin resistance occurred in
      1993 when newer macrolides became available and were widely used in the latter
      part of 1992. CONCLUSION: The data show that frequent testing for resistance to
      erythromycin of group A beta-haemolytic streptococci is required for the use of
      this antibiotic in our country.

PMID- 8874112
TI  - Staff attitudes towards continuation of life-support in newborns with major
      congenital anomalies.
AB  - This study was conducted to gain insight into the attitudes of medical staff
      towards life-support of newborns with life-threatening problems, seen against the
      background of these children's expected morbidity and quality of life. The
      opinions about the mode of life-support were determined by questionnaires and the
      demographic characteristics of the respondents were noted. Each patient's risk of
      mortality was scored by means of the standardized Paediatric Risk of Mortality
      Score (PRISM). Attitudes towards support were unanimous for 39 of the 46
      patients. For the other 7 patients at least one of the respondents preferred a
      different support mode than that given at the time. The attitudes were influenced
      by the patient's risk of mortality. CONCLUSION: Decisions about life-support of
      newborns with life-threatening problems should include all the disciplines
      involved in patient care and should be made at an early stage.

PMID- 8874113
TI  - Autosomal dominant familial Mediterranean fever--like syndrome.
AB  - We report a syndrome characterized by recurrent episodes of fever and serositis
      in an Austrian family. Three family members over two successive generations were
      affected. The febrile episodes had their onset at the age of 11-12 years, lasted
      1-5 weeks, and occurred in intervals of 6-24 months. While the disorder resembles
      familial Mediterranean fever (FMF) clinically, ethnic distribution and other
      features suggest a distinct entity. Clinically, the attacks last longer than the
      usual FMF attacks, and in the male patients are associated with scrotal
      inflammation. Genetically, the disorder appears to be inherited as an autosomal
      dominant syndrome, whereas FMF is autosomal recessive. Molecular analysis made
      the involvement of a gene in the FMF region of chromosome 16p13.3 highly
      unlikely. CONCLUSION: An Austrian family with recurrent fever syndrome is
      reported. Ethnicity, clinical features, and molecular studies point to a distinct
      clinical entity.

PMID- 8874114
TI  - Renal-hepatic-pancreatic dysplasia: an autosomal recessive disorder with renal
      and hepatic failure.
AB  - We report two brothers with renal dysplasia and congenital hepatic fibrosis. One
      patient died shortly after birth of lung hypoplasia. The second developed end
      stage renal failure at 14 months. The hepatic fibrosis progressed to cirrhosis
      and hepatic failure. Pancreatic function was normal, but increased echogenicity
      was seen on ultrasound. At age 3 years and 9 months a successful combined liver
      kidney transplantation was performed. The features of our patients are compatible
      with the "renal-hepatic-pancreatic dysplasia" syndrome. CONCLUSION: Renal-hepatic
      pancreatic dysplasia is an autosomal recessive disorder with variable expression.
      Combined liver-kidney transplantation offers a new therapeutic option.

PMID- 8874115
TI  - Case report. Microcephalic osteodysplastic primordial dwarfism type II: a child
      with unusual symptoms and clinical course.
AB  - We report on a 13-month old boy with microcephalic osteodysplastic primordial
      dwarfism (MOPD), whose radiographic signs correspond with type II of this entity.
      Some of his clinical signs, such as the anomalies of the external genitalia and
      the urinary tract, are common to this subgroup of MOPD, but he also shows unusual
      clinical signs including bilateral knee dislocation and hypoplasia of the
      anterior corpus callosum. His clinical course was unusual with several episodes
      of breathing difficulties and increased intracranial pressure secondary to
      craniosynostosis at the age of 16 months. After front-orbital advancement for the
      treatment of brachycephaly, his psychomotor development improved remarkably.
      CONCLUSION: MOPD type II may have a wider range of expression than previously
      delineated.

PMID- 8874116
TI  - Two cases of maternal antenatal splenic rupture and hypotension associated with
      Moebius syndrome and cerebral palsy in offspring. Further evidence for a utero
      placental vascular aetiology for the Moebius syndrome and some cases of cerebral
      palsy.
AB  - We wish to report two cases of congenital abnormality after antenatal car
      accidents resulting in ruptured spleen and severe hypotension in the mothers at 8
      and 14 weeks gestation. The first case had the classical Moebius syndrome with
      6th and 7th cranial nerve palsy with abnormal brain stem evoked responses,
      presumably due to hypoxic/ischaemic brain stem damage and the second case had
      severe retardation and hypertonic cerebral palsy which at post mortem was found
      to be due to old hypoxic/ischaemic lesions to the caudate nucleus putamen and
      striatum. CONCLUSION: The cases described provide evidence that severe maternal
      hypotension during pregnancy can be associated with lesions to the midbrain and
      brain stem of offspring. The mechanism is probably utero-placental insufficiency,
      and extrapolation from these two unusual cases would support utero-placental
      insufficiency as a cause of Moebius syndrome and limb deficiency after chorionic
      villus sampling.

PMID- 8874117
TI  - Reaction of term newborns with prolonged postnatal dyspnoea to early oxygen, mask
      continuous positive airway pressure, and volume expansion: a prospective,
      randomised, clinical trial.
AB  - In a prospective, randomised, open trial 103 term newborns with persisting
      dyspnoea, tachypnoea and/or cyanosis were treated with oxygen for 5-10 min and
      then with oxygen plus mask continuous positive airway pressure (CPAP) for another
      5-15 min. Cases with overt prenatal or intrapartum obstetric pathology had been
      excluded from the study. Forty-one infants (40%) responded to this procedure
      within 10-25 min. The remaining 62 infants (60%) were randomly allocated to one
      of three forms of further treatment: continuation of mask CPAP for 20 min (group
      A, n = 24), volume expansion with 9 ml of 3 ml albumin, 3 ml glucose, and 3 mEq
      of sodium bicarbonate (group B, n = 24), or volume expansion with 4.5 ml albumin
      and 4.5 ml glucose (group C, n = 14). There was no statistical difference in
      birth weight, gestational age or Apgar scores at 1 and 5 min between the infants
      of the groups. Time to normalisation of symptoms was significantly shorter in the
      volume expansion groups (B: 45 +/- 41 min, range 20-180, and C: 80 +/- 72 min,
      range 20-210) than in the mask CPAP group (A; 224 +/- 256 min, range 30-1200, P =
      0.02). There were statistical differences in umbilical cord and capillary pH
      values among the infants of the three groups, but the response to therapy was not
      related to the degree of acidaemia. Thirty-four infants (33%) who did not respond
      were admitted to a special care unit for further examination (group A: 21/24,
      group B: 7/24; group C: 6/14). Of these, 23 had no abnormal findings, 8 infants
      had radiological signs of transitory respiratory distress, and 1 had a non
      tension pneumothorax. Septicaemia was found in two infants. No infant was
      intubated. At discharge all 103 infants did well. CONCLUSION: Incremental
      application of simple primary care procedures including volume expansion (with or
      without alkali) in term newborns with persisting postnatal tachypnoea and
      dyspnoea helps avoid overtreatment and unnecessary separation from the mothers in
      most cases and reliably selects infants who need close monitoring or special
      treatment.

PMID- 8874118
TI  - Circulating interleukin-1 receptor antagonist levels in neonates.
AB  - Circulating interleukin-1 receptor antagonist (IL-1 Ra) levels have been shown to
      reflect disease activity in certain conditions in adults. We determined
      circulating IL-1Ra references values for healthy neonates (healthy preterms and
      term infants with mild disease only) on days 2 (n = 17) and 4 of life (n = 23).
      Mean gestational age was 35 +/- 2.6 weeks. On the 2nd day of life IL1-Ra levels
      were 0.78 ng/ml (0.49/2.65), on day 4 0.38 ng/ml (0.20/0.48) (median, 25th/75th
      percentile, P = 0.01). The values were not influenced by gender. In neonates with
      severe illness (septicaemia, asphyxia, neonatal respiratory distress syndrome),
      who received invasive intensive care, circulating IL-1Ra levels were
      significantly higher than in the reference group of healthy newborns. On the 2nd
      day of life (14.72 ng/ml (4.38/18.67) versus 0.78 ng/ml (0.49/2.65), P < 0.0001;
      on day 4 of life, 3.38 ng/ml (0.80/11.99) versus 0.38 ng/ml (0.20/0.48), P <
      0.005 (values are median; 25th/75th percentile, Mann-Whitney U-Wilcoxon Rank Sum
      W Test, two-tailed P). CONCLUSION: Compared to healthy individuals beyond the
      neonatal period, Il-1Ra concentrations are physiologically elevated within the
      first days of life and decline to low levels within days. In contrast, IL-1Ra
      levels are strikingly elevated in sick neonates.

PMID- 8874119
TI  - Serum creatinine concentration, urinary creatinine excretion and creatinine
      clearance during the first 9 weeks in preterm infants with a birth weight below
      1500 g.
AB  - Little is known about serum creatinine concentration, urinary creatinine
      excretion and creatinine clearance in preterm infants. The aim of the present
      study was to establish age related reference values for the first weeks of life
      in preterm infants with a birth weight < 1500 g. In addition, the possible
      influence of therapy with dexamethasone, spironolactone and catecholamines was
      investigated. In 34 patients, serum creatinine, urinary creatinine excretion and
      creatinine clearance were measured at weeks 1, 2, 3,-4, 5-6 and 7-9 of life.
      Median birth weight was 1225 g (range 730-1495), mean gestational age 29 (range
      26-34) weeks. Concentration of creatinine in serum and urine, urinary creatinine
      excretion per kilogram body weight and creatinine clearance showed a significant
      correlation with postnatal age. Thus age related reference values as proposed
      given in the present study are desirable. Median serum creatinine concentration
      decreased continuously within the first weeks of life: 97 (10-90th percentile: 69
      141) in the 1st week, 70 (45-99) in the 2nd week, 57 (39-71) at week 3-4, 51 (42
      62) at week 5-6 and 44 (39-48) mumol/l at week 7-9. Median creatinine output in
      mumol/kg body weight was 100 (10-90th percentile: 62-160) in the 1st week, 92 (65
      120) in the 2nd week, 79 (52-122) at week 3-4, 89 (68-106) at week 5-6 and 86 54
      109) mumol/kg/d at week 7-9. Creatinine clearance increased significantly within
      the first weeks of life. Values were 12.5 (10-90 the percentile: 7-22) in the 1st
      week, 16 (10-28) in the 2nd week, 20 (11-34) at weeks 3-4, 23 (15-36) at weeks 5
      6 and 29 (17-36) ml/min per 1.73 m2 at weeks 7-9. Therapy with dexamethasone,
      spironolactone or catecholamines showed no influence on creatinine excretion.
      Creatinine clearance did not only depend on postnatal age but also on gestational
      age and on the necessity of mechanical ventilation. These findings indicate a
      reduced glomerular filtration rate in very mature and severely ill preterm
      infants. CONCLUSION: It might be necessary to lower dosage of renal excreted
      drugs in very immature and mechanically ventilated infants according to the
      creatinine clearance.

PMID- 8874120
TI  - Sedation for children undergoing magnetic resonance imaging: efficacy and safety
      of rectal thiopental.
AB  - The need to reappraise sedation policy is dictated by newer noninvasive imaging
      modalities. In this study we evaluate the safety and efficacy of rectally
      administered thiopental in children undergoing MRI. Eighty-three consecutive
      patients with congenital heart disease (mean age 2.9 years, SD 2.5) undergoing
      MRI evaluation of the heart were given thiopental (25-50 mg/kg, 700 mg max) per
      rectum. In order to prevent leakage, a female urinary catheter was used. In 79
      patients (95.2%) successful sedation was achieved and adequate MR imaging could
      be obtained. In 4 patients (4.8%) the sedation was inadequate. Respiratory
      depression was not encountered in any of the patients. The presence of cyanotic
      congenital heart disease in 26 patients had no influence on the safety and
      efficacy of thiopental. All successfully sedated children were asleep within 30
      min and adequate sedation was maintained for at least 45 min. All patients could
      be aroused within 90 min, and sent home thereafter. Minor side-effects occurred
      in two patients. CONCLUSION: Rectally-administered thiopental is a safe and
      effective sedative drug with a duration of action tailored to performing MRI.

PMID- 8874121
TI  - Respiratory morbidity in young school children born prematurely--chronic lung
      disease is not a risk factor?
AB  - Children born prematurely and recruited into a prospective follow up study were
      examined at 5 years of age. Our aim was to determine aetiological associations of
      respiratory symptoms in such children and, in particular, to determine the
      importance of severe chronic lung disease (CLD, oxygen dependence beyond 36 weeks
      post conceptional age). Respiratory status was documented from parental history
      in 103 children of median gestational age 29 weeks (range 23-35), 17 of whom had
      suffered from severe CLD. In 90 of the 103 children lung function had been
      assessed at 1 year of age. Regression analysis revealed that neither severe CLD
      nor other perinatal variables, but only a family history of atopy, significantly
      related to a positive symptom status. A high airways resistance at 1 year also
      significantly related to positive symptom status. CONCLUSION: Reduction in severe
      CLD (oxygen dependence beyond 36 weeks postconceptional age) may make relatively
      little impact on respiratory morbidity in young school children born prematurely.

PMID- 8874123
TI  - Leptin concentrations in amniotic fluid, venous and arterial cord blood and
      maternal serum: high leptin synthesis in the fetus and inverse correlation with
      placental weight.

PMID- 8874122
TI  - Case of the month: a newborn with tachypnoea and consolidation of the right lung.

PMID- 8874124
TI  - Congenital rickets.

PMID- 8874125
TI  - The association of cystic fibrosis with homocystinura in two Saudi siblings.

PMID- 8874126
TI  - Tetrahydrobiopterin induced neonatal tyrosinaemia.

PMID- 8874127
TI  - Failure of beta interferon therapy in X-linked adrenoleukodystrophy.

PMID- 8874128
TI  - Urinary uric acid excretion and renal function in newborn infants.

PMID- 8874129
TI  - Novelty-associated locomotion: correlation with cortical and sub-cortical GABAA
      receptor binding.
AB  - The present study was designed to determine whether variability in GABA (eta
      aminobutyric acid)A receptor binding in cortical and subcortical brain regions
      was correlated with locomotor activity in a novel environment. Twenty four
      animals were rated for locomotor activity in a novel circular runway. Eight days
      later, locomotor activity was assessed following 1.5 mg/kg amphetamine sulfate
      (i.p.). After four to six days, animals were killed and samples were pooled in
      groups of four animals ranked according to novely locomotor score, and specific
      binding of the GABAA receptor antagonist [2-(3'-carboxy-2'-propyl)-3-amino-6-p
      methoxy phenylpyridazinium bromide] ([3H]SR95531) was determined. Significant
      negative correlations were seen between specific ([3H]SR95531) binding and
      novelty induced locomotion in the cingulate and prefrontal cortices, and in the
      ventral pallidum. A near-significant negative correlation was seen in the
      striatum. Correlation coefficients between locomotion scores in the novel
      environment and specific [3H]SR95531 binding were: cingulate cortex, R = -0.91, P
      = 0.012; prefrontal cortex, R = -0.85, P = 0.032; ventral pallidum, R = -0.85, P
      = 0.030; striatum, R = -0.73, P = 0.097; and nucleus accumbens, R = -0.09, P =
      0.85. The positive correlation between novelty- and amphetamine-induced
      locomotion was also quite high (R = 0.95, P = 0.004). These results are discussed
      in terms of their relevance to potential biochemical correlates of drug abuse
      vulnerability.

PMID- 8874130
TI  - Metrifonate improves spatial navigation and avoidance behavior in scopolamine
      treated, medial septum-lesioned and aged rats.
AB  - We investigated the effects of acute p.o. pretraining treatment with an indirect
      acetylcholinesterase inhibitor, metrifonate, on water maze spatial navigation and
      passive avoidance behavior. Metrifonate (10-100 mg/kg, orally, p.o.) did not
      improve the water maze or passive avoidance performance of young intact rats.
      However, in young rats metrifonate over a broad dosage range (10-100 mg/kg, p.o.)
      was able to alleviate the adverse effects of scopolamine (a muscarinic
      acetylcholine receptor antagonist; 0.4 and 2.0 mg/kg in water maze and passive
      avoidance study, respectively) and medial septum-lesioning on spatial reference
      and working memory and passive avoidance performance. In old (23-month-old) rats,
      a defect of water maze and passive avoidance behavior was observed. In old rats,
      metrifonate improved spatial reference memory function in the water maze and also
      passive avoidance at 10-30 mg/kg, but the 3 mg/kg dose was ineffective. Very old
      (27-month-old) rats had a more severe impairment of water maze performance than
      old rats, and metrifonate 3-30 mg/kg did not improve their spatial navigation.
      These results show that metrifonate may over a wide range of doses stimulate
      cognitive functioning, but during advanced aging neurobiological defects develop
      that may mask some of the therapeutic effects of metrifonate in rats.

PMID- 8874131
TI  - Drug states as modulators of conditioned immobility in a latent discrimination
      procedure.
AB  - Midazolam, amphetamine, and flesinoxan were used in four rat experiments to
      examine the usefulness of a latent Pavlovian discrimination procedure to assess
      the discriminative-stimulus, or occasion-setting, properties of drugs. Experiment
      1 first assessed the unconditioned effect of each of the drugs on the dependent
      measure used, which was immobility. Relative to saline, midazolam enhanced
      immobility, whereas flesinoxan, and especially amphetamine decreased it. In each
      of the Experiments 2-4, subjects received a limited number of training sessions
      during which they consistently received a footshock in a distinctive box after a
      drug but not after saline, or vice versa. Subsequently, non-reinforced test
      sessions were performed in the drug and saline states in both the conditioning
      box and a novel box. Relative to the saline state, rats previously shocked under
      midazolam were less mobile in the conditioning box under midazolam, whereas rats
      previously not shocked under amphetamine or flesinoxan were more mobile under the
      drug. The remaining animals did not show differential responding. The response
      profiles were accounted for in terms of the combined operation of an associative,
      or occasion-setting, effect and a non-associative effect of the drug-induced
      states.

PMID- 8874132
TI  - Studies on the role of 5-HT3 receptors in the mediation of the ethanol
      interoceptive cue.
AB  - The drug discrimination test was used to evaluate the role of 5-HT3 receptors in
      the mediation of the stimulus properties of ethanol in rats trained to
      discriminate between ethanol (1.0 g/kg, 10% v/v, i.p.) and saline vehicle. Rats
      trained to discriminate between a lower dose of ethanol (0.5 g/kg i.p.) failed to
      attain discrimination criteria after 20 weeks (100 sessions) of training. None of
      the doses of 5-HT3 receptor antagonists (0.001, 0.01, 0.1, 1.0, 10.0 mg/kg of
      tropisetron or ondansetron) administered i.p. 30 min before ethanol, antagonized
      the discriminative stimulus properties of ethanol. Furthermore, none of the
      centrally (1, 10, 35 micrograms per rat) or i.p. (0.1, 1.0, 2.5, 5.0, 10.0 mg/kg)
      administered doses of 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide, could
      replace the ethanol discriminative cue. These results suggest that 5-HT3
      receptors are not primarily involved in the mediation of the stimulus properties
      of ethanol.

PMID- 8874133
TI  - (+)-SKF-10,047 and dextromethorphan ameliorate conditioned fear stress via
      dopaminergic systems linked to phenytoin-regulated sigma 1 sites.
AB  - Mice exhibited a marked suppression of motility when they were re-placed in the
      same environment in which they had previously received an electric footshock. (+)
      SKF-10,047 ([2S-(2 alpha, 6 alpha, 11R*)]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3
      (2-propenyl)-2,6-me tha no-3-benzazocin-8-ol hydrochloride; (+)-N
      allylnormetazocine hydrochloride) and dextromethorphan, putative sigma receptor
      agonists, have been reported to reserve this psychological stress-induced motor
      suppression, defined as conditioned fear stress, through phenytoin-regulated type
      sigma 1, receptors. In the present study, we investigated the involvement of
      dopaminergic neurons in the ameliorating effects of (+)-SKF-10,047 and
      dextromethorphan on conditioned fear stress. (+)-SKF-10,047 and dextromethorphan
      attenuated conditioned fear stress at low doses (4 and 20 mg/kg, respectively)
      when they were co-administered with phenytoin (10 mg/kg), an anticonvulsant drug.
      The effects were antagonized by the sigma receptor antagonists. NE-100 (N,N
      dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride) and
      BMY-14802 (a-(4-fluoro-phenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol
      hydrochloride). Furthermore, the effects of (+)-SKF-10,047 or dextromethorphan in
      combination with phenytoin were blocked by the dopamine D1 receptor antagonist.
      SCH 23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-
      benzazepine), and the dopamine D2 receptor antagonist, (-)-sulpiride, and they
      were also attenuated by 6-hydroxydopamine-induced lesions of dopaminergic
      neurons. The ameliorating effects of (+)-SKF-10,047 and dextromethorphan on
      conditioned fear stress at high doses (5 and 30 mg/kg, respectively) were also
      blocked by both the dopamine receptor antagonists. These results suggest that the
      stress-induced motor suppression is restored by the activation of dopaminergic
      neuronal systems as a result of the stimulation of phenytoin-regulated type sigma
      1 receptors.

PMID- 8874134
TI  - Structurally modified ibogaine analogs exhibit differing affinities for NMDA
      receptors.
AB  - Based on both preclinical findings and anecdotal evidence in man, the
      psychoactive indole alkaloid ibogaine has been suggested to have anti-addictive
      properties. Previous studies indicate that blockade of NMDA receptors may mediate
      at least some of the putative anti-addictive actions of ibogaine. The potencies
      of a series of ibogaine analogs to inhibit (+)-[3-3H]5-methyl-10,11-dihydro-5H
      dibenzo-[a,d]cyclohepten-5,10- imine ([3H]MK-801) binding to NMDA receptors were
      examined. This series of analogs included the putative ibogaine metabolite O
      desmethylibogaine, its metabolism resistant analog O-t-butyl-O-desmethylibogaine,
      the iboga alkaloids (+/-)-ibogamine, (+/-)-coronaridine, tabernanthine,
      harmaline, and the indolotropanes endo-3-(1-methylindol-2-yl)-8-methyl-8
      azabicyclo[3.2.1]loctane (RS 075194-190), exo-3-(1-methylindol-2-yl)-8-methyl-8
      azabicyclo[3.2.1]octane (RS 075237-190), and endo-3-(indol-2-yl)-8-methyl-8
      azabicyclo[3.2.1]octane (RS 025989-190). Among these compounds, ibogaine was the
      most potent inhibitor of [3H]MK-801 binding (Ki = approximately 1.2 microM),
      whilst the compounds with the greatest structural similarity to ibogaine, O
      desmethylibogaine and O-t-butyl-O-desmethylibogaine were less potent (Ki =
      approximately 5.5 and 179.0 microL, respectively). In morphine-dependent mice,
      ibogaine, but not O-desmethylibogaine or O-t-butyl-O-desmethylibogaine,
      attenuated naloxone precipitated withdrawal jumping. These findings are
      consistent with the hypothesis that inhibition of the expression of morphine
      dependence by ibogaine is related to its NMDA receptor antagonist properties.

PMID- 8874135
TI  - Developmental regulation of regional functionality of substantial nigra GABAA
      receptors involved in seizures.
AB  - GABAergic (gamma-aminobutyric acid) transmission in the substantia nigra pars
      reticulata is critical for seizure control. We tested the hypothesis that there
      is a differential regional distribution and functionality of nigral GABAA
      receptor sites that is developmentally regulated. In adult rats, we determined
      the effects on flurothyl seizures of (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic
      acid (ZAPA, a presumed agonist of the low-affinity GABAA receptor site),
      bicuculline (an antagonist of the low-affinity GABAA receptor site) and gamma
      vinyl-GABA (a GABA-transaminase inhibitor), infused bilaterally in anterior or
      posterior substantia nigra pars reticulata. ZAPA infusions (8 micrograms) were
      anticonvulsant in anterior substantia nigra but proconvulsant in posterior
      substantia nigra. Bicuculline infusions (100 ng) were proconvulsant in anterior
      substantia nigra but ineffective in posterior substantia nigra. An anticonvulsant
      dose of gamma-vinyl-GABA, when infused in anterior substantia nigra, was
      proconvulsant when infused in posterior substantia nigra. In 15 day old rats, the
      effects of ZAPA, were biphasic: 2 micrograms was anticonvulsant while 8
      micrograms was proconvulsant. There was no regional specificity. The data suggest
      that with maturation there is functional segregation of specific GABAA receptor
      subtypes involved in substantia nigra-mediated seizure control.

PMID- 8874136
TI  - Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats.
AB  - Vascular reactivity and activation of the nitric oxide (NO) pathway were
      investigated in perfused mesenteric vascular bed removed from rats 5 h after i.p.
      injection of bacterial lipopolysaccharide (E. coli lipopolysaccharide, 30 mg kg 
      1). Lipopolysaccharide treatment induced hyporesponsiveness to noradrenaline.
      Maximal noradrenaline-induced vasoconstriction was significantly reduced in
      lipopolysaccharide-treated vs. untreated preparations. Continuous infusion of L
      arginine (L-Arg) (0.2 mM) enhanced noradrenaline hyporeactivity of
      lipopolysaccharide-treated rats. N omega-Nitro-L-arginine methyl ester (L-NAME)
      (0.2 mM), a non-selective inhibitor of NO synthase, failed to completely restore
      the noradrenaline hyporeactivity of lipopolysaccharide-treated + L-Arg-infused
      mesenteric vascular bed. After L-NAME treatment. Methylene blue (10 microM), a
      guanylate cyclase inhibitor, produced no additional increase of noradrenaline
      vasoconstriction in lipopolysaccharide-treated + L-Arg-infused mesenteric
      vascular bed, suggesting that an NO-independent activation of guanylate cyclase
      may be excluded. In lipopolysaccharide-treated preparations, L-Arg (0.2 mM)
      elicited a significant increase in nitrite production, which was antagonized by L
      NAME. In conclusion, lipopolysaccharide-induced noradrenaline hyporesponsiveness
      of rat resistance vessels can only be partially explained by NO overproduction.
      Other mechanisms, probably related to vasoconstriction, may be involved.

PMID- 8874137
TI  - U50,488H-induced pressor effect in the ovine foetus is mediated by sympathetic
      activation and vasopressin.
AB  - The purpose of this study was to investigate the mechanism behind the increase in
      blood pressure observed after intravenous administration of U50,488H (trans-3,4
      dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide), a selective Kappa
      opioid receptor agonist, to the ovine foetus. Intravenous administration of
      U50,488H (1.0 mg/kg) to the foetus resulted in an immediate increase in foetal
      blood pressure which lasted 15 min. Pretreatment with phentolamine (1.0 mg/kg
      i.v.) completely blocked the immediate (1-4 min) pressor effect of U50,488H, but
      not the subsequent increase in blood pressure after 5 min. In contrast,
      pretreatment with the vasopressin antagonist ([beta-mercapto-beta, beta
      cyclopentamethylene-propionyl)-O-Me2-Tyr,Arg8]vasopressin, 0.06 mg/kg) did not
      affect the immediate pressor effect of U50,488H, but completely blocked the
      latter increase in blood pressure after 4 min. These data suggest that the
      immediate increase in blood pressure caused by U50,488H was mediated by
      sympathetic activation which was then further sustained by a release of
      vasopressin.

PMID- 8874138
TI  - The actions of ketotifen on intestinal smooth muscles.
AB  - Ketotifen is a tricyclic drug with a wide spectrum of pharmacological effects. We
      studied the actions of ketotifen on the mechanical activity of isolated segments
      of guinea-pig ileum, guinea-pig colon and mouse colon. In the guinea-pig ileum
      ketotifen induced small contractions and inhibited the contractions induced by
      carbachol and by electric field stimulation. Responses to bradykinin (in the
      absence or in the presence of atropine 1 microM) were similarly inhibited by
      ketotifen, with an IC50 of 23 microM. In the guinea-pig colon ketotifen evoked
      non-cholinergic contractions with a pD2 of 4.5, but still it inhibited responses
      to bradykinin (IC50 = 75 microM). Ketotifen relaxed the unstimulated mouse colon
      with a pD2 of 4.2. This effect persisted in the presence of propranolol and
      phentolamine (each 10 microM). Incubation of the mouse colon with the nitric
      oxide synthase inhibitors NG-nitro-L-Arginine methyl ester hydrochloride (L
      NAME), or L-NG-nitro-arginine (L-NNA) (100-500 microM) did not alter the
      inhibitory action of ketotifen. The histamine H1 receptor antagonist
      chlorpheniramine (5 microM) or the nerve blocker tetrodotoxin (1 microM) did not
      alter the inhibitory effects of ketotifen. It is concluded that the actions of
      ketotifen are mediated by a non-cholinergic, non-histaminergic mechanisms.

PMID- 8874139
TI  - A non peptidic corticotropin releasing factor receptor antagonist attenuates
      fever and exhibits anxiolytic-like activity.
AB  - The multiple actions of corticotropin-releasing factor (CRF) on neuroendocrine
      and behavioural functions can now be examined using new, high affinity, non
      peptidic antagonists which exhibit central activity upon systemic application. We
      have shown that compound CP 154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6
      trimethylphenyl)-7H-pyrrolo [2,3-d]pyrimidin-4-yl]amine) displaces
      [125I][Tyr0]CRF from rat hippocampal CRF receptors (IC50 = 0.5 nM) and from
      pituitary CRF receptors (IC50 = 0.04 nM). The same compound inhibits in a
      concentration-dependent manner the ovine CRF (0.1 microM)-stimulated adenylate
      cyclase activity in membranes of a mouse pituitary adenoma cell line, AtT20, with
      an IC50 value of 50 nM. Systemic application of the CRF receptor antagonist (0.16
      mg/kg i.p.) blocked recombinant human interleukin-1 beta 5 micrograms/kg i.p.)
      induced fever in rats. The CRF receptor antagonist CP 154,526 (1 mg/kg i.p.) also
      exhibited signs of anxiolytic-like activity in the elevated plus-maze test in
      rats.

PMID- 8874140
TI  - Differential changes of myocardial beta-adrenoceptor subtypes and G-proteins in
      dogs with right-sided congestive heart failure.
AB  - We have shown previously in dogs with right heart failure that the reduction of
      myocardial beta-adrenoceptor density occurs only in the failing right ventricle,
      while cardiac inotropic responses to beta-adrenergic stimulation are reduced in
      both the right and left ventricles. The purpose of the present study was to
      determine whether a post-receptor defect in the guanine nucleotide-binding
      regulatory proteins (G-proteins) existed which would explain, at least in part,
      the adrenergic subsensitivity in both ventricles of the heart failure dogs. Using
      both immunoblotting technique and the bacterial toxin-mediated ADP ribosylation
      assays, we found that the stimulatory G-protein (Gs) was reduced in both
      ventricles of the heart failure dogs. In contrast, there were no changes in the
      inhibitory G-protein (Gi). In addition, receptor subtype analysis showed that
      only beta(1)-adrenoceptors were reduced in the failing right ventricle of the
      heart failure animals. This study demonstrated that the reduction of beta
      adrenoceptors in right heart failure was chamber-specific whereas the reduction
      of Gs was non-selective, occurring in both ventricles of right heart failure
      dogs. The findings further suggest that the reduction of Gs probably was caused
      by systemic neurohormonal activation, independent of local ventricular stress.

PMID- 8874141
TI  - Biotransformation of glyceryl trinitrate by blood platelets as compared to
      vascular smooth muscle cells.
AB  - The present study investigated the metabolism of glyceryl trinitrate by washed
      human platelets as compared to that by rat vascular smooth muscle cells. Possible
      changes in metabolism after induction of nitrate tolerance were also studied in
      both systems. Incubation of the cells with glyceryl trinitrate (0.1 mM) resulted
      in a time-dependent release of nitrite (NO2-) amounting to 6.30 +/- 0.63 nmol mg
      protein-1 h-1 in vascular smooth muscle cells and 0.61 +/- 0.08 nmol mg protein-1
      h-1 for platelets, respectively. The nitric oxide (NO) scavenger, oxyhemoglobin
      (10 microM), significantly reduced NO2- generation in both cell types studied.
      Nitrate tolerance was induced by incubation of the cells with glyceryl trinitrate
      (2 mM) for 2 h. In tolerant vascular smooth muscle cells as well as in tolerant
      platelets, NO2- release was significantly reduced. The inhibitory capacity of
      glyceryl trinitrate on ADP (6 microM)-induced platelet aggregation and on
      intracellular Ca2+ signals was significantly reduced in tolerant platelets. The
      data show a direct metabolism of glyceryl trinitrate by human blood platelets
      which is subject to a type of tolerance development similar to that in vascular
      smooth muscle cells.

PMID- 8874142
TI  - Mood stabilizers have differential effects on endogenous ADP ribosylation in C6
      glioma cells.
AB  - Bipolar disorder is associated with increased levels and function of the G
      protein, Gs alpha which may be normalized by treatment with mood stabilizing
      medications (i.e. lithium salts and the anticonvulsants, valproic acid and
      carbamazepine). In C6 glioma cells, endogenous ADP ribosylation was markedly
      increased by lithium chloride (+83%, P < 0.005), decreased by valproic acid (
      48%, P = 0.07) whereas carbamazepine had no effect. Since ADP ribosylation of Gs
      alpha has been shown to increase turnover of this protein these results suggest a
      possible mechanism of action for lithium chloride. These results also suggest
      that lithium salts and the anticonvulsant mood stabilizers may have distinct
      mechanisms of action.

PMID- 8874143
TI  - Effects of 5-HT4 receptor antagonists on rat behaviour in the elevated plus-maze
      test.
AB  - The anxiolytic-like effects of a variety of 5-HT receptor agonists and
      antagonists have been intensively studied in animal models. However, no direct
      effects of agents modulating 5-HT4 receptors have been reported, in spite of
      their suggestive location in the brain. The objective of the present study was
      the determination of the effects of two selective 5-HT4 receptor antagonists, SB
      204070 [1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5
      carboxylate] and GR 113808 [[1-[2-methylsulphonyl)amino]ethyl]-4
      piperidinyl]methyl 1-methyl-1 H-indole-3-carboxylate], in the elevated plus-maze
      test in rats. Results have shown that both 5-HT4 receptor antagonists exhibit an
      anxiolytic-like profile, although only at the dose of 1.0 mg/kg (s.c.). At this
      dose, both compounds significantly increased the percentage of time spent in open
      arms exploration, while other variables evaluated remained unaffected at the dose
      range tested. Results suggest that 5-HT4 receptor antagonists could have some
      anxiolytic-like properties, although their effects seem more limited and less
      consistent than those presented by classic anxiolytics, such as diazepam.
      However, they are similar to those exhibited by granisetron [endo-1-methyl-N-(9
      methyl-9-azabicyclo[3.3.1]non-3-yl)-1 H-indazole-3-carboxamide], a 5-HT3 receptor
      antagonist.

PMID- 8874144
TI  - Interleukin-1 receptor antagonist does not reverse lipopolysaccharide-induced
      inhibition of water intake in rat.
AB  - The involvement of interleukin-1 in antidipsogenic effects induced by
      intraperitoneal (i.p.) administration of lipopolysaccharide (0.32, 0.64 and 0.96
      mg/kg) in 24-h water-deprived rats, was evaluated by injection of human
      interleukin-1 receptor antagonist (10, 25 and 50 micrograms/rat) into the lateral
      cerebral ventricle (i.c.v.). The effects of either lipopolysacharide or human
      interleukin-1 receptor antagonist treatment on rectal temperature of 24-h water
      deprived rats, were examined. Our date show that human interleukin-1 receptor
      antagonist administration is able to reverse, dose dependently, fever, but not
      lipopolysaccharide inhibition of thirst. The reduction of pyrogenic, but not of
      antidipsogenic, effects of lipopolysaccharide following human interleukin-1
      receptor antagonist administration suggests that lipopolysaccharide inhibition of
      thirst is not dependent on interleukin-1 induced fever and that interleukin-1 is
      not a direct mediator implicated in inhibition of water intake provoked by
      peripheral injection of lipopolysaccharide.

PMID- 8874145
TI  - Ventral tegmental injection of nicotine induces locomotor activity and L-DOPA
      release from nucleus accumbens.
AB  - Effects of nicotine systemically or locally on locomotor activity and L-3,4
      dihydroxyphenylalanine (L-DOPA) release were studied using microdialysis in the
      nucleus accumbens of freely moving rats. The basal L-DOPA release was Ca2(+)
      dependent and tetrodotoxin-sensitive. Systemic nicotine (1 mg/kg s.c.) increased
      locomotor activity and L-DOPA release preferentially in the nucleus accumbens as
      compared with the striatum. Injection of nicotine (30 micrograms) into the
      ventral tegmental area increased locomotor activity and L-DOPA release from the
      nucleus accumbens. These increases were antagonized by prior injection of
      mecamylamine into the ventral tegmental area. Nicotine induces locomotor activity
      and L-DOPA release from the nucleus accumbens via nicotinic receptors in the
      ventral tegmental area. The release may be relevant to behavioral actions of
      nicotine.

PMID- 8874146
TI  - Elevated myocardial interstitial norepinephrine concentration contributes to the
      regulation of Na+,K(+)-ATPase in heart failure.
AB  - Myocardial Na+,K(+)-ATPase is reduced in congestive heart failure. To study the
      regulation of Na+,K(+)-ATPase in congestive heart failure, we performed Western
      and Northern blot analyses of ventricular myocardium of dogs with pacing-induced
      congestive heart failure and chronic norepinephrine infusion, using isoform
      specific antibodies and cDNA probes. Congestive heart failure and norepinephrine
      infusion caused similar increases in myocardial interstitial norepinephrine
      concentration and reductions of myocardial Na+,K(+)-ATPase alpha 3-subunit
      protein, but differed in their effects on myocardial Na+,K(+)-ATPase alpha 3
      subunit gene expression. Chronic norepinephrine infusion produced no changes in
      the steady-state mRNA level for the alpha 3-subunit of Na+,K(+)-ATPase,
      suggesting that the changes in Na+,K(+)-ATPase protein were induced via a post
      transcriptional mechanism. In contrast, down-regulation of the Na+,K(+)-ATPase
      alpha 3-subunit in the failing heart was accompanied by a decreased alpha 3
      subunit mRNA level, indicating the presence of a transcriptional event. The alpha
      1-subunit protein content and mRNA level were not affected by either
      norepinephrine infusion or rapid ventricular pacing. We conclude that, while
      elevated myocardial interstitial norepinephrine levels may contribute
      substantially to the down-regulation of the Na+,K(+)-ATPase alpha 3-subunit in
      the failing myocardium, additional regulatory factors are responsible for the
      decreased myocardial alpha 3-subunit mRNA expression in congestive heart failure.

PMID- 8874147
TI  - Influence of cAMP on cerebrospinal fluid opioid concentration: role in cAMP
      induced pial artery dilation.
AB  - Previously, it has been observed that cGMP analogs and agents that elevate cGMP
      levels markedly increase the concentration of the opioids [Met5]enkephalin and
      [Leu5]enkephalin in cortical periarachnoid cerebrospinal fluid (CSF) of the
      newborn pig. However, such agents had no effect on CSF dynorphin-(1-13)
      concentration. The present study was designed to: (1) investigate the influence
      of cAMP on the CSF concentration of the opioids [Met5]enkephalin,
      [Leu5]enkephalin and dynorphin-(1-13); and (2) determine the role of these
      opioids in cAMP-induced pial artery vasodilation. Piglets equipped with closed
      cranial windows were used to measure pial artery diameter and collect cortical
      periarachnoid CSF for assay of opioids. The cAMP analog, 8-Bromoadenosine-3',5'
      cyclic monophosphate (8-Bromo cAMP) elicited pial dilation that was blunted by a
      cAMP antagonist, Rp 8-Bromoadenosine-3',5'-cyclic monosphorothioate (10(-5) M)
      (11 +/- 1 and 19 +/- 1 vs. 1 +/- 1 and 1 +/- 1 for 10(-8) M, 10(-6) M 8-Bromo
      cAMP before and after Rp 8-Bromoadenosine-3',5'-cyclic monosphorothioate,
      respectively). The dilation produced by 8-Bromo cAMP was accompanied by modest
      increases in CSF [Met5]enkephalin and co-administration of Rp 8-Bromoadenosine
      3',5'-cyclic monosphorothioate with 8-Bromo cAMP blocked these increases in CSF
      opioid concentration (1179 +/- 48, 1593 +/- 92 and 2079 +/- 88 vs. 1054 +/- 32,
      1038 +/- 15 and 1071 +/- 17 pg/ml for control, 10(-8) M and 10(-6) M 8-Bromo cAMP
      before and after Rp 8-Bromoadenosine-3',5'-cyclic monosphorothioate,
      respectively). The release of CSF [Leu5]enkephalin by 8-Bromo cAMP was also
      blocked by Rp 8-Bromoadenosine-3',5'-cyclic monosphorothioate. In contrast 8
      Bromo cAMP produced marked increases in CSF dynorphin-(1-13) (38 +/- 3, 61 +/- 3
      and 88 +/- 6 vs. 27 +/- 3, 28 +/- 3 and 30 +/- 4 pg/ml for control, 10(-8) M and
      10(-6) M 8-Bromo cAMP before and after Rp 8-Bromoadenosine-3',5'-cyclic
      monosphorothioate, respectively). Similar blunted vascular and biochemical
      responses were observed with the co-administration of Sp 8-Bromoadenosine-3',5'
      cyclic monophosphorothioate, another analog of cAMP, with Rp 8-Bromoadenosine
      3',5'-cyclic monosphorothioate. The opioid receptor antagonist naloxone (1 mg/kg
      i.v.) attenuated 8-Bromo cAMP-induced dilation (9 +/- 1 and 17 +/- 1 vs. 5 +/- 1
      and 8 +/- 1 for 10(-8) M, 10(-6) M 8-Bromo cAMP before and after naloxone). These
      data show that cAMP contributes to the release of the CSF opioids
      [Met5]enkephalin, [Leu5]enkephalin and dynorphin-(1-13), and suggest that, while
      cGMP is more important relative to cAMP in elevating CSF [Met5]enkephalin and
      [Leu5]enkephalin concentration, the converse is true for dynorphin-(1-13).
      Further, these data indicate that opioids contribute to cAMP-induced pial artery
      vasodilation.

PMID- 8874148
TI  - Analysis of responses to angiotensin I and angiotensin I-(3-10) in the mesenteric
      vascular bed of the cat.
AB  - Responses to angiotensin I and antiogensin I-(3-10), the precursors for
      angiotensin II and IV, were investigated in the mesenteric vascular bed of the
      cat. Under constant-flow conditions, injections of precursors and the active
      peptides into the mesenteric arterial perfusion circuit caused dose-related
      increases in receptor antagonist that were attenuated by the angiotensin AT1
      receptor antagonist DuP532 (2-propyl-4-pentafluorethyl-1-[2'-(2H-tetrazol-5-YL)
      1,1'-bi phenyl-4-YL methyl]1H-imidazole-5-carboxylic acid), but not by the
      angiotensin AT2 receptor antagonist PD123,319 ((S)1-[[4-(dimethylamino)-3
      methylphenyl]methyl]-5-(diphenylacetyl )-4,5,6,7- tetrahydro-1H-imadazo[4,5
      c]pyridine-6-carboxylic acid, ditriflouroacetate]). Responses to angiotensin I
      and II were similar as were responses to angiotensin I-(3-10) and angiotensin IV,
      and these responses were not altered by the presence of a time-delay coil in the
      perfusion circuit. Responses to angiotensin I and angiotensin I-(3-10) were
      decreased by the angiotensin converting enzyme inhibitor enalaprilat in a dose of
      the angiotensin converting enzyme inhibitor that had no effect on responses to
      angiotensin II and IV and that enhanced vasodilator responses to bradykinin. The
      putative angiotensin AT2 receptor agonist, p-aminophenylalanine6-angiotensin II,
      produced dose-related increases in mesenteric arterial perfusion pressure that
      were reduced by DUP532, suggesting that they are mediated by angiotensin AT1
      receptors. These results suggest that angiotensin I and angiotensin I-(3-10) are
      rapidly and efficiently converted by an angiotensin converting enzyme-dependent
      pathway into active peptides that induce vasoconstriction by activating
      angiotensin AT1 receptors in the mesenteric vascular bed of the cat.

PMID- 8874149
TI  - An orally active non-selective endothelin receptor antagonist, bosentan, markedly
      reduces injury in a rat model of colitis.
AB  - Activation of endothelial cells by vasoactive mediators, such as endothelins, may
      be an early, strategically important step in the initiation of inflammation in
      the intestine. In view of recent evidence that inflammatory bowel disease is
      associated with elevated intestinal concentrations of endothelins and upregulated
      expression of endothelin receptors on vascular endothelium in intestine,
      endothelins may become therapeutic targets in inflammatory bowel disease. The
      recent availability of an orally active, mixed endothelin receptor antagonist,
      bosentan, allowed us to examine the role of endothelins in a rat model of
      colitis. Colitis was induced by intra-rectal administration of trinitrobenzene
      sulphonic acid. In each treatment group, rats were treated with bosentan (10-60
      mg/kg p.o.) 24 and 2 h prior to (pre-dose) or 1 h after the induction (post
      induction) of colitis and all animals were treated every 24 h thereafter for 5
      days. On day 6, stool consistency and the presence of adhesions in the peritoneal
      cavity were accessed. Colonic tissue samples were removed for determination of
      macroscopic and microscopic tissue injury, and myeloperoxidase activity. Colitis
      was typified by tissue ulceration in the distal colon and a corresponding 35-fold
      increase in myeloperoxidase activity compared to non-inflamed controls. Daily
      treatment with bosentan dose-dependently reduced colonic damage and
      myeloperoxidase activity when bosentan was given prior to induction of colitis.
      In the pre-dose group, the greatest beneficial effect of bosentan was observed at
      60 mg/kg; colonic damage and granulocyte infiltration were attenuated by > 80%. A
      partial therapeutic effect of bosentan was also observed at 60 mg/kg when the pre
      treatment regimen was excluded. These findings demonstrate that an orally active,
      mixed endothelin receptor antagonist has marked protective and therapeutic
      effects in an animal model of colitis.

PMID- 8874150
TI  - Human colonic mucosa possesses a mixed population of 5-HT receptors.
AB  - The aim of this study was to characterise the 5-HT receptor(s) mediating
      secretory responses of isolated human colonic mucosa to 5-HT. Sheets of muscle
      stripped mucosa from proximal (ascending) and distal (sigmoid) human colon were
      set up in Ussing chambers for measurement of short-circuit current (Isc). Serosal
      application of 5-HT led to non-neural, concentration-dependent increases in Isc.
      Desensitisation to 5-HT was observed with ascending and sigmoid colonic mucosa.
      Using selective 5-HT antagonists we have shown that 5-HT induces secretion in
      sigmoid colon via a 5-HT2A receptor. In ascending colon a combination of 5-HT2A
      and 5-HT4 receptors appears to be involved.

PMID- 8874151
TI  - Effect of intracerebroventricularly injected choline on plasma ACTH and beta
      endorphin levels in conscious rats.
AB  - In the present study, we examined the effect of intracerebroventricularly
      injected choline on plasma ACTH (adrenocorticotrophin) and beta-endorphin levels
      in conscious rats. The intracerebroventricularly injection of choline (50-150
      micrograms) elevated plasma ACTH levels in a dose-dependent manner. Plasma beta
      endorphin levels were also significantly increased. Pretreatment of rats with
      mecamylamine (50 micrograms; intracerebroventricularly), the nicotinic receptor
      antagonist, completely inhibited the ACTH and beta-endorphin response to choline
      (150 micrograms; intracerebroventricularly). An antagonist of the muscarinic
      receptor, atropine (10 micrograms; intracerebroventricularly), failed to alter
      these effects. Pretreatment of rats with hemicholinium-3 (20 micrograms;
      intracerebroventricularly), a drug which inhibits the uptake of choline into
      cholinergic neurons, abolished the choline-induced increases in both plasma ACTH
      and beta-endorphin levels. These results indicate that choline can increase
      plasma concentrations of ACTH and beta-endorphin through the activation of
      central nicotinic acetylcholine receptors.

PMID- 8874152
TI  - Adrenaline release by the 5-HT1A receptor agonist 8-OH-DPAT is partly responsible
      for pituitary activation.
AB  - In male Wistar rats the effect of adrenalectomy on pituitary activation by the 5
      HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), was
      studied. Rats were injected intravenously with 8-OH-DPAT (0.10 mg/kg) in their
      home cages. Blood samples were withdrawn from freely moving cannulated rats for
      determination of plasma adrenaline and plasma adrenocorticotropin hormone (ACTH).
      Adrenalectomized rats showed almost no measurable amounts of plasma adrenaline,
      but these animals had elevated baseline plasma (ACTH levels as compared to sham
      operated rats. 8-OH-DPAT treatment led to a large plasma adrenaline response in
      the sham-operated animals, which was abolished after adrenalectomy. The plasma
      ACTH response to 8-OH-DPAT was significantly diminished in the adrenalectomized
      rats as compared to sham animals. This blunted ACTH response in adrenalectomized
      rats, however, was still considerable in magnitude. The present data thus
      indicate that the plasma ACTH response to 8-OH-DPAT is due to at least two
      different mechanisms. First, via 5-HT1A receptor-mediated adrenaline release,
      which may consequently stimulate the pituitary. Second, a direct action of 8-OH
      DPAT on hypothalamic 5HT1A receptors is assumed, independent of peripheral
      adrenaline release.

PMID- 8874153
TI  - Pharmacology of the nicotinic acetylcholine receptor from fetal rat muscle
      expressed in Xenopus oocytes.
AB  - The fetal rat muscle nicotinic acetylcholine receptor was expressed in Xenopus
      oocytes. Using the voltage-clamp technique, the response to a range of agonists
      was measured, listed in order of (decreasing) activity efficacy: anatoxin > or =
      epibatidine > acetylcholine > DMPP (1,1-dimethyl-4-phenylpiperazinium) > >
      cytisine > pyrantel > nicotine > coniine > tubocurare > lobeline. The agonist
      responses were compared with the steric and electrostatic properties of the
      molecules, using molecular modelling. Single-channel current were measured in
      outside-out patches for acetylcholine, nicotine, cytisine, anatoxin and
      epibatidine. The conductance of the single channels was independent of the type
      of agonist. The mean open times were characteristic of the agonist applied.
      Tubocurare, better known for its antagonist properties, was also a partial
      agonist. Single-channel currents were also observed for tubocurare, and for
      methyllycaconitine in patches with a very high density of the muscle nicotinic
      acetylcholine receptor, and these were blocked by alpha-bungarotoxin. The agonist
      properties of physostigmine, galanthamine and their methyl derivatives were also
      investigated. The conductance of the channels observed in outside-out patches was
      similar to that obtained for the classical agonists. The single-channel currents
      observed for physostigmine, galanthamine and their methyl derivatives were
      blocked by alpha-bungarotoxin, methyllycaconitine and mecamylamine, in contrast
      to previously reported studies on neuronal and adult muscle nicotinic
      acetylcholine receptors.

PMID- 8874154
TI  - Characterization of YM90K, a selective and potent antagonist of AMPA receptors,
      in rat cortical mRNA-injected Xenopus oocytes.
AB  - The inhibitory potencies of 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)
      quinoxalinedione hydrochloride (YM90K), 2-3,dihydroxy-6-nitro-7-sulfamoyl
      benzo(F)quinoxaline (NBQX) and 1-(4-amino-phenyl)-4-methyl-7,8-methyl-endioxyl-5H
      2,3-benzodiazep ine (GYKI 52466) at excitatory amino acid receptors were examined
      in rat cortical mRNA-injected Xenopus oocytes using a two-electrode voltage
      clamp. Schild analysis of YM90K and NBQX inhibition of kainate currents yielded
      pA2 values of 6.83 +/- 0.01 and 7.24 +/- 0.01, respectively. GYKI 52466 reduced
      the maximum kainate response and increased the kainate EC50 in a dose-dependent
      manner, suggesting that the antagonism of AMPA receptors by GYKI 52466 is mixed
      competitive and non-competitive for kainate. Schild analysis of YM90K and NBQX
      inhibition of kainate currents in the presence of 30 microM cyclothiazide yielded
      pA2 values of 6.62 +/- 0.03 (slope: 1.02 +/- 0.01) and 7.10 +/- 0.02 (slope: 1.00
      +/- 0.02), respectively, consistent with competitive antagonism. Cyclothiazide
      potentiated the AMPA response as well as the kainate response and increased the
      apparent Hill coefficients in a concentration-dependent manner. The potency of
      YM90K to inhibit AMPA-induced current could be reduced by increasing the
      concentration of cyclothiazide. We showed that YM90K is a potent and competitive
      antagonist for AMPA receptors and the apparent affinity of competitive
      antagonists was reduced by cyclothiazide. Cyclothiazide can affect the
      interaction between receptors and both agonists and antagonists, suggesting that
      it might allosterically alter the affinity of agonists and competitive
      antagonists for their binding site on the AMPA receptor complex.

PMID- 8874155
TI  - N-Methyl-D-aspartate-induced enhancement of activator protein-1 DNA binding
      activity is blocked by ethanol in cerebellar granule cells.
AB  - The effects of ethanol on N-methyl-D-aspartate (NMDA) and non-NMDA receptor
      agonist-stimulated activator protein-1 (AP-1) DNA binding activity in primary
      cultures of rat cerebellar granule cells were investigated. The application of
      intoxicating concentrations of ethanol produced a concentration-dependent
      inhibition of NMDA-enhanced AP-1 binding with a significant reduction obtained at
      50 mM ethanol. The inhibitory actions of ethanol on alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid (AMPA)-stimulated AP-1 binding were
      considerably weaker as compared to the effects seen following administration of
      NMDA. The AMPA-induced enhancement of AP-1 DNA binding activity was demonstrated
      both in the absence and presence of cyclothiazide, a drug, which is known to
      block the desensitization of AMPA receptors. Our data suggest that moderate
      concentrations of ethanol modulate glutamate-induced alterations of gene
      expression in brain neurons.

PMID- 8874156
TI  - Ageing is associated with changes in glutamate release, protein tyrosine kinase
      and Ca2+/calmodulin-dependent protein kinase II in rat hippocampus.
AB  - We have used synaptosomes prepared from rat hippocampus to investigate the role
      of protein tyrosine kinase and Ca2+/calmodulin-dependent protein kinase II in
      modulating glutamate release in young animals and to investigate possible
      parallel age-related changes in release and kinase activity. We report that
      depolarization of synaptosomes with 40 mM KCl, which stimulated glutamate
      release, also significantly increased activity of both kinases, while the protein
      tyrosine kinase inhibitor, genistein and the Ca2+/calmodulin-dependent protein
      kinase II inhibitor, KN62 (1-(N,O-bis[5-isoquinolinesulfonyl]-N-methyl-tyrosyl)-4
      phenylpiperax ine) decreased K(+)-stimulated, Ca2(+)-dependent release of
      glutamate. K(+)-stimulated release of glutamate was significantly decreased in
      hippocampal synaptosomes prepared from aged, compared to young, animals. In
      parallel with these changes in release, we report an age-related decrease in
      activities of both protein tyrosine kinase and Ca2+/calmodulin-dependent protein
      kinase II. We conclude that these kinases play a role in modulating release of
      glutamate in hippocampus and that the age-related decrease in glutamate release
      may be partly due to an age-related decrease in kinase activities.

PMID- 8874157
TI  - Stereoselectivity of Ca2+ channel block by dihydropyridines: no modulation by the
      voltage protocol.
AB  - The L-type Ca2+ current inhibition by the enantiomers of the dihydropyridine
      niguldipine was investigated at various holding potentials (-40 to -120 mV) and
      stimulus frequencies (0.1-1 Hz), using guinea-pig ventricular myocytes. Block of
      whole-cell current is both voltage- and concentration-dependent. (S)-Niguldipine
      is more potent than its (R)-enantiomer. However, the extent of enantioselectivity
      is rather small (< or = x 4.4). Importantly, this value does not increase when
      stimulus conditions favour the inactivated channel state, although this leads to
      more potent block. This is in contrast to our expectation based on modulated
      receptor hypothesis, and to the high enantioselectivity of niguldipine binding
      found in guinea-pig heart membranes (x 40). We conclude that the common modulated
      receptor hypothesis had to be refined to explain the effects of niguldipine
      enantiomers.

PMID- 8874158
TI  - The synergism between ACPD and arachidonic acid on glutamate release in
      hippocampus is age-dependent.
AB  - Activation of the metabotropic glutamate receptor by the specific agonist trans-1
      amino-cyclopentyl-1,3-dicarboxylate (ACPD) increases release of glutamate and
      activation of protein kinase C in the presence of a low concentration of
      arachidonic acid in hippocampal synaptosomes prepared from 4-month-old rats. The
      data presented indicate an age-related decrease in both [3H]glutamate release and
      protein kinase C activation and an age-related decrease in the release response
      to arachidonic acid and ACPD, with no corresponding change in protein kinase C
      activation. The finding that the interaction between arachidonic acid and ACPD on
      release was absent in synaptosomes prepared in the presence of heparin, an
      antagonist at inositol trisphosphate receptors, suggests that mobilization of
      intracellular calcium stores plays a role in the synergism between arachidonic
      acid and ACPD on [3H]glutamate release in hippocampal synaptosomes.

PMID- 8874159
TI  - Clinical experience with percutaneous dilatational tracheostomy: report of 150
      cases.
AB  - OBJECTIVE: To report our experience with percutaneous dilatational tracheostomy.
      DESIGN: Retrospective study. SETTING: Teaching hospital. The Netherlands.
      SUBJECTS: 147 patients. INTERVENTIONS: 150 percutaneous dilatational
      tracheostomies, 95 (63%) for prolonged ventilation, 37 (25%) for pulmonary
      toilet, and 18 (12%) for upper airway obstruction. MAIN OUTCOME MEASURES:
      Morbidity and mortality. RESULTS: The success rate of the procedure was 99%.
      Operative complications occurred in 16 (11%) and were usually minor. During a
      total duration of cannulation of 5212 days four complications were recorded.
      Haemorrhage was the most common early complication (n = 14). Late complications
      (five to 53 months after decannulation) included tracheal stenosis (n = 1),
      tracheomalacia (n = 2), tracheocutaneous fistula (n = 2) and an ugly scar (n =
      1). CONCLUSION: Percutaneous dilatational tracheostomy is a simple, safe and cost
      effective technique for inserting a tracheal cannula.

PMID- 8874160
TI  - The effect of pretreatment with endotoxin and lactobacillus on bacterial
      translocation in acute liver injury.
AB  - OBJECTIVE: To evaluate the effect of pretreatment with endotoxin or Lactobacillus
      reuteri pretreatment on bacterial translocation after acute liver injury. DESIGN:
      Experimental study. SETTING: University department, Sweden. SUBJECTS: 96 Sprague
      Dawley rats were divided into four groups of 24 each. Three of them received
      intraperitoneal D-galactosamine, the fourth received pyrogen free water and was
      used as the normal control. Twenty-four hours later the study was terminated and
      samples collected. INTERVENTIONS: Endotoxin and L reuteri R2LC were injected
      intraperitoneally three days, one week, and two weeks before induction of liver
      injury. MAIN OUTCOME MEASURES: Extent of liver injury and bacterial translocation
      to mesenteric lymph nodes, liver, and systemic blood. RESULTS: The extent of
      liver injury and rate of bacterial translocation were lower three days after
      pretreatment with endotoxin, than after pretreatment with L reuteri. There was no
      other difference among the other groups. High concentrations of serum endotoxin
      were detected three days after pretreatment with endotoxin. There were no
      significant changes in small intestinal and caecal bacterial counts. CONCLUSION:
      Pretreatment with endotoxin effectively prevented liver injury by D-galactosamine
      and subsequent bacterial translocation. Pretreatment with L reuteri had no
      beneficial effect.

PMID- 8874161
TI  - Duodenum preserving resection of the head of the pancreas in painful chronic
      pancreatitis.
AB  - OBJECTIVE: Evaluation of duodenum preserving resection of the head of the
      pancreas in patients with disabling pain caused by chronic pancreatitis with an
      inflammatory mass in the head of the pancreas. DESIGN: Retrospective study.
      SETTING: University hospital. The Netherlands. SUBJECTS: 15 consecutive patients.
      MAIN OUTCOME MEASURES: Mortality, morbidity, pain relief, endocrine and exocrine
      function. RESULTS: There was no 30 day postoperative mortality. Early morbidity
      consisted of small bowel leak (n = 1), obstructive ileus (n = 1) and peri
      anastomotic abscess (n = 2). Relief of pain was achieved in 13 patients (86%)
      after a mean follow up of 37 months; 11 (73%) were totally free of pain, and 2
      (13%) had improved. Neither endocrine nor exocrine function deteriorated
      significantly after resection. CONCLUSION: Duodenum preserving resection is an
      effective operation in patients with disabling pain caused by chronic
      pancreatitis with an inflammatory mass in the head of the pancreas.

PMID- 8874162
TI  - Implantation metastases from gastrointestinal cancer after percutaneous puncture
      or biliary drainage.
AB  - OBJECTIVE: Evaluation of incidence and outcome of implantation metastases after
      percutaneous fine-needle biopsy or biliary drainage. DESIGN: Retrospective study.
      SETTING: University hospital, Sweden. SUBJECTS: Eight patients with implantation
      metastases from gastrointestinal cancers after percutaneous fine-needle biopsy (n
      = 7) or biliary drainage (n = 1). MAIN OUTCOME MEASURES: Incidence of
      implantation metastases, treatment and influence on outcome and survival.
      RESULTS: In two out of three patients who had had otherwise radical operations,
      the implantation metastases meant that the operations were palliative rather than
      curative. Patients who had had palliative resections of the implantation
      metastases developed major local complications. One patient is alive with no
      signs of disease after 106 months, while one is alive with disease 30 months
      after the diagnosis of the implantation metastases. The remaining patients have
      died after 6 to 23 months. CONCLUSION: The incidence of implantation metastases
      after fine-needle procedures is probably underestimated. There is a slight but
      definite risk that the procedure may render an otherwise curative resection
      palliative. Implantation metastases cause local complaints of varying severity
      and seems to have a tendency to recur locally. We recommend that fine-needle
      biopsy should be restricted to patients who will truly benefit from a more
      accurate preoperative diagnosis.

PMID- 8874163
TI  - Coloanal anastomosis for benign lesions: long term functional results in 11
      patients.
AB  - OBJECTIVE: To assess the indications, morbidity, and long-term functional results
      of rectal resection and coloanal anastomosis for benign rectal lesions. DESIGN:
      Retrospective study. SETTING: Teaching hospital, France. SUBJECTS AND
      INTERVENTIONS: Eleven patients were operated on for villous adenoma (n = 5),
      radiation proctitis (n = 2), solitary rectal ulcer (n = 2), rectal stenosis (n =
      1) and rectovaginal fistula (n = 1). MAIN OUTCOMES MEASURES: Morbidity,
      mortality, and long-term results. RESULTS: There were no postoperative deaths. 2
      patients (18%) developed major postoperative complications: one pelvic abscess
      was treated conservatively and one anastomotic fistula required a diverting
      colostomy. The mean (SD) follow-up period was 89 (35) months. Functional results
      were judged as perfect (n = 4), good (n = 1), or acceptable (n = 2) (mean stool
      frequency: 1.4), including the five with villous adenoma, one with radiation
      proctitis, and the one with a rectovaginal fistula. By the end of the follow-up
      period, 4 patients (36%) had permanent colostomies (including the two patients
      with solitary rectal ulcers). Two of them were required soon after operation, and
      two following failure 5 and 2 years later, respectively, after initially good
      functional results. CONCLUSION: Rectal resection with coloanal anastomosis can
      safely be proposed for selected patients with benign rectal lesions including
      diffuse villous adenoma, rectovaginal fistula, and radiation proctitis without
      deterioration of the anal sphincter. The poor results in the 2 cases of solitary
      rectal ulcer suggest that for this condition coloanal anastomosis should be done
      only after the failure of previous surgical treatment.

PMID- 8874164
TI  - Quantification of intestinal blood flow by ultrasonic transit time flowmetry in
      fed and endotoxaemic rats.
AB  - OBJECTIVE: To compare the dye dilution method with ultrasonic transit time
      flowmetry (UTTF) for quantifying intestinal blood flow in the same experimental
      animals. DESIGN: Open experimental study. SETTING: University hospital, Osaka,
      Japan. MATERIAL: 11 (experiment 1) and 25 (experiment 2) adult male Sprague
      Dawley rats. INTERVENTIONS: In experiment 1, the rats were fasted overnight. In
      experiment 2, endotoxin, Escherichia coli lipopolysaccharide (endotoxin) or
      saline (sham) was injected intraperitoneally. MAIN OUTCOME MEASURES: Superior
      mesenteric venous and abdominal aortic blood flow. RESULTS: Experiment 1:
      intestinal blood flow measured by UTTF was significantly decreased by 17% (p <
      0.05) and 56% (p < 0.05) after 30 minutes infusion through the tertiary branch of
      the mesenteric vein and during simultaneous drawing of blood samples from both
      the carotid artery and the superior mesenteric vein over a 1.5 minute period,
      respectively. The intestinal blood flow measurements obtained by UTTF at
      different intervals before simultaneous drawing of blood from the carotid artery
      and the superior mesenteric vein differed significantly (p < 0.05) from those
      obtained by the dye dilution method. Experiment 2: intestinal blood flow was also
      decreased by 21%-34% (p < 0.05) during similar simultaneous drawing of blood.
      Aortic blood flow in the endotoxin group was reduced by 66% (p < 0.05) compared
      with fed animals and 63% (p < 0.05) compared with sham animals. Simultaneously,
      intestinal blood flow in the endotoxin group was also reduced by 57% (p < 0.05)
      compared with fed or 48% (p < 0.05) compared with sham treated animals.
      CONCLUSION: Real intestinal blood flow might not be measured by the procedure of
      simultaneously drawing blood from the carotid artery and the superior mesenteric
      vein in rats as is usually done in the dye dilution method. Intraperitoneal
      endotoxin reduced aortic as well as intestinal blood flow. We propose that UTTF
      is an alternative method for quantifying intestinal blood flow in fed and
      endotoxaemic animals.

PMID- 8874166
TI  - Obstructive jaundice and bacterial translocation.

PMID- 8874165
TI  - Effects of obstructive jaundice and external biliary diversion on bacterial
      translocation in rats.
AB  - OBJECTIVE: To find out the rate of translocation of bacteria to visceral organs
      in obstructive jaundice, and whether the absence of bile within the intestine or
      the presence of obstructive jaundice itself promotes bacterial translocation.
      DESIGN: Prospective, controlled experimental animal study. SETTING: University
      hospital, Turkey. SUBJECTS: 40 Inbred albino rats weighing 160-220 g.
      INTERVENTIONS: Three groups of rats were studied: sham operated controls (n =
      15), ligation of the common bile duct (CBD) (n = 15), and CBD-ligation and
      proximal external biliary division through a Silastic catheter (n = 10).
      Specimens of distal small bowel mesenteric lymph nodes (MLN), liver, spleen, and
      lung were obtained on the 10th postoperative day, and quantitative
      bacteriological analysis done. Caecal aerobic microflora were also measured for
      qualitative and quantitative comparisons. RESULTS: The translocation of bacteria
      to MLN, liver, and spleen, but not to the lungs, was slightly but not
      significantly increased by ligation of the CBD. Ligation of the CBD with
      simultaneous external biliary diversion caused increase translocation to all
      organs examined (with the increases to the MLN (p = 0.012), liver (p = 0.009),
      and spleen (p = 0.028) being significant). There was no difference in the raised
      bacterial counts in MLN and visceral organs after ligation of the CBD or biliary
      diversion. The pattern of caecal microflora did not change in any group.
      CONCLUSIONS: These findings suggest that the absence of bile from the gut may
      promote bacterial translocation to visceral organs.

PMID- 8874167
TI  - Idiopathic sclerosing encapsulating peritonitis.

PMID- 8874168
TI  - Pseudomembranous colitis presenting as an acute abdomen.

PMID- 8874169
TI  - Generalised lymphangioleiomyomatosis presenting as a retroperitoneal tumour.

PMID- 8874170
TI  - Septic ovarian vein thrombophlebitis: a surgical disease that should be treated
      without operation.

PMID- 8874171
TI  - Duplication of the vermiform appendix.

PMID- 8874172
TI  - The role of extraction in stability of orthodontic treatment.
AB  - Long-term postretention assessment of orthodontically treated cases has been of
      interest for 5 decades; however, extraction versus nonextraction follow-up
      studies are difficult to compare without regard to sample structure, therapy
      concept und different parameters. The results of selected studies- extraction of
      1 or 2 incisors, of premolars and of second and third molars, early and late
      extraction therapy and serial extraction-showed that long-term postretention
      stability is not a realistic treatment goal. The Cologne long-term records allow
      optimistic prediction: relative stability has been found in the majority of
      former patients, irrespective of the kind of treatment and treatment time.
      Original anomaly, type (extraction/nonextraction) and amount of treatment, and
      end-of-treatment alignment were found to be major factors influencing
      dentoalveolar and skeletal post-treatment changes. The conclusion is that therapy
      induced post-treatment changes can be reduced by having a treatment goal within
      the anatomic limits.

PMID- 8874173
TI  - Skeletal and dentoalveolar changes after extraction of the second molars in the
      upper jaw.
AB  - The aim of this study was to evaluate treatment results after extraction of
      maxillary second molars. Since this therapy was chosen in patients with class II
      malocclusion, deep overbite and counterclockwise growth pattern, its effects on
      overbite and correction of the malocclusion were examined. For this purpose pre-
      and post-treatment models of 25 patients with 48 extracted upper second molars
      were measured and lateral cephalograms were appropriately superimposed in order
      to determine maxillary and mandibular skeletal and dentoalveolar changes. Our
      results indicate an average overbite reduction from 4.7 mm to 2.7 mm. None of the
      patients showed a posttreatment overbite increase. Despite the considerable
      initial Class II relation in many cases, a Class I occlusion was achieved in 92%
      of the patients. Primarily, the correction was achieved by distalization of the
      upper first molars. Furthermore, the mesial migration of the lower first molars,
      skeletal changes in the lower jaw, and the growth inhibition in the upper jaw
      contributed to the correction of the class II malocclusion.

PMID- 8874174
TI  - Concept and development of a measuring system for in vivo recording of
      orthodontically applied forces and torques in the multiband technique. Part I.
AB  - The cause of tooth movement with a multiband or multibracket appliance is the
      force system in the bracket, which is generated by an archwire and transmitted by
      a bracket to the respective tooth. Continuous arch wires are, from the
      biomechanical point of view, a statically multiply undetermined system.
      Quantitative determination of the forces and torques acting at the individual
      teeth, and thus observance of a non-critical level of applied forces, is
      therefore extremely problematic in practice, the force is applied by the
      orthodontist more or less "intuitively" on the basis of recommendations evolved
      in theory and in vitro. The measuring technique presented in this paper is
      designed to permit these force systems to be recorded in vivo for the first time,
      allowing account to be taken of the individual situation "tooth-periodontium
      bone". Evolvement of an appropriate measuring principle was followed by
      development of the individual components of the measuring system. The results of
      the subsequent initial in vitro test series offer the prospect of successful
      clinical application.

PMID- 8874175
TI  - Instant assessment of pulpal blood flow after orthodontic force application.
AB  - The purpose of the present investigation was to measure the effect of tooth
      intrusion and extrusion on pulpal blood flow in man. The flow changes were
      measured in 10 lateral incisors (6 subjects) by means of laser Doppler flowmetry
      (Perimed, Sweden) applied on the buccal surface through metal tubes bonded to the
      teeth. Brackets were bonded onto teeth 13 and 23, and intrusive and extrusive
      forces of 2 N were applied in random order to the experimental tooth for 5 min
      before unloading. The contralateral tooth served as a control. Extrusion of the
      teeth gave no significant changes in pulpal blood flow during loading or
      unloading. However, intrusion of the teeth reduced the pulpal blood flow by 20%
      during the first minute after force application. The pulpal blood flow gradually
      increased towards the preloading flow values for the next 4 min, and was returned
      to the prestimulus level 3 min after unloading. In conclusion orthodontic
      intrusion of teeth with a 2 N force evoked a temporary reduction in the pulpal
      blood flow, whereas extrusion had no effect on the pulpal blood flow.

PMID- 8874176
TI  - The soft tissue cover of the mandibular condyle: age-related changes in high
      buoyant density proteoglycans, free tissue water and remodelling activity.
AB  - Age-related changes in the relative proportion of high buoyant density
      proteoglycans of the soft tissue cover of the mandibular condyle of domestic pigs
      and the chemical composition of these proteoglycans were investigated by
      biochemical methods. The relative proportion of high buoyant density
      proteoglycans has been shown to decrease with age, with their chemical
      composition varying as follows: With age, the relative proportions of protein
      increased, galactosamine decreased, glucosamine was similar in newborns and
      juveniles, but clearly increased in adults, galactosamine plus glucosamine
      decreased. As measured by 1H-NMR-relaxation spectroscopic methods, the
      concentration of free tissue water of the soft tissue cover of the mandibular
      condyle decreased with age. Its mobility, however, was greater in newborns than
      in juveniles, but similar in juveniles and adults. The concentration of free
      tissue water, but not its mobility, correlated weakly with relative proportions
      of polyanionic side chains (e.g. chondroitin sulphate plus keratan sulphate
      chains) of the high buoyant density proteoglycans. By affecting the concentration
      of free tissue water and in turn of matrix solutes and cellular environments, the
      high buoyant density proteoglycans of the soft tissue cover of the mandibular
      condyle seem to be involved in regulation of age-related changes in the adaptive
      remodelling activity of the mandibular condyle.

PMID- 8874177
TI  - Biologic and clinical effects of granulocyte colony-stimulating factor in normal
      individuals.

PMID- 8874178
TI  - The PML/RAR alpha oncoprotein is a direct molecular target of retinoic acid in
      acute promyelocytic leukemia cells.
AB  - Acute promyelocytic leukemia (APL) is characterized by the translocation,
      t(15;17) and the expression of a PML/RAR alpha fusion protein that is diagnostic
      of the disease. There is evidence that PML/RAR alpha protein acts as a dominant
      negative inhibitor of normal retinoid receptor function and myeloid
      differentiation. We now show that the PML/RAR alpha fusion product is directly
      downregulated in response to retinoic acid (tRA) treatment in the human APL cell
      line, NB4. tRA treatment induces loss of PML/RAR alpha at the protein level but
      not at the level of mRNA, as determined by Northern blots, by Western blots, and
      by ligand binding assays and in binding to RA-responsive DNA elements. We present
      evidence that this regulation is posttranslational. This evidence suggests that
      tRA induces synthesis of a protein that selectively degrades PML/RAR alpha. We
      further show that this loss of PML/ RAR-alpha is not limited to the unique APL
      cell line. NB4, because PML/RAR alpha protein is selectively downregulated by tRA
      when expressed in the transfected myeloid cell line U937. The loss of PML/RAR
      alpha may be directly linked to tRA-induced differentiation, because in a
      retinoid-resistant subclone of NB4, tRA does not decrease PML/RAR alpha protein
      expression. In NB4 cells, the specific downregulation of the fusion protein
      decreases the ratio of PML/RAR alpha to wild-type RAR alpha. Because the ratio of
      expression of PML/RAR alpha to wild-type RAR alpha and PML may be important in
      maintaining the dominant negative block of myelocytic differentiation, these data
      suggest a molecular mechanism for restoration by tRA normal myeloid
      differentiation in APL cells.

PMID- 8874179
TI  - Cloning and characterization of human SHIP, the 145-kD inositol 5-phosphatase
      that associates with SHC after cytokine stimulation.
AB  - We recently cloned and sequenced a cDNA encoding a 145-kD protein from the murine
      hematopoietic cell line B6SUtA, that becomes tyrosine phosphorylated and
      associated with Shc after cytokine stimulation. Based on its domains and
      enzymatic activity, we named this protein SHIP for SH2-containing inositol
      phosphatase (Damen et al, Proc Natl Acad Sci USA 93:1689, 1996). We describe here
      the cloning of the human homologue of murine SHIP (mSHIP) from a human
      megakaryocytic cell line (MO7e) lambda gt11 cDNA library using two nonoverlapping
      mSHIP cDNA fragments as probes. Northern blot analysis suggests that human SHIP
      (hSHIP) is expressed as a 5.3-kb mRNA in human bone marrow and a wide variety of
      other tissues. Sequence analysis of this cDNA predicts a protein of 1188 amino
      acids exhibiting 87.2% overall sequence identity with mSHIP. Contained within the
      defined open reading frame is an N-terminal, group l src homology 2 (SH2) domain;
      three NXXY motifs that, if phosphorylated, could be bound by phosphotyrosine
      binding (PTB) domains; a C-terminal proline-rich region; and two centrally
      located inositol polyphosphate 5-phosphatase motifs. Fluorescence in situ
      hybridization, using the full-length hSHIP cDNA as a probe, mapped hSHIP to the
      long arm of chromosome 2 at the border between 2q36 and 2q37.

PMID- 8874180
TI  - A randomized investigation of high-dose versus standard-dose cytosine arabinoside
      with daunorubicin in patients with previously untreated acute myeloid leukemia: a
      Southwest Oncology Group study.
AB  - Interest in high-dose cytarabine (HDAC) for both induction and postremission
      therapy for acute myeloid leukemia (AML) prompted the Southwest Oncology Group
      (SWOG) to initiate a randomized trial comparing HDAC with standard-dose
      cytarabine (SDAC) for remission induction of previously untreated AML and to
      compare high-dose treatment versus conventional doses for consolidation therapy.
      Patients less than 65 years of age with de novo or secondary AML were randomized
      for induction between SDAC 200 mg/ m2/d for 7 days by continuous infusion or HDAC
      at 2 g/ m2 intravenously every 12 hours for 12 doses; both groups received
      daunorubicin (DNR) at 45 mg/m2/d intravenously for 3 days. Complete responders to
      SDAC were randomized to receive either two additional courses of SDAC plus DNR or
      one course of HDAC plus DNR. Complete responders to HDAC were nonrandomly
      assigned to receive one additional course of HDAC plus DNR. Of patients
      randomized between SDAC (n = 493) and HDAC (n = 172) induction, 361 achieved
      complete remission (CR). The CR rate was slightly poorer with HDAC: 55% versus
      58% with SDAC for patients aged less than 50, and 45% (HDAC) versus 53% (SDAC)
      for patients aged 50 to 64 (age-adjusted one-tailed P = .96). With a median
      follow-up time of 51 months, survival was not significantly better with HDAC (P =
      .41); the estimated survival rate at 4 years was 32% (HDAC) versus 22% (SDAC) for
      those aged less than 50, and 13% (HDAC) versus 11% (SDAC) for those aged 50 to
      64. However, relapse-free survival was somewhat better following HDAC Induction
      (P = .049): 33% (HDAC) versus 21% (SDAC) at 4 years for those aged less than 50,
      and 21% (HDAC) versus 9% (SDAC) for those aged 50 to 64. Induction with HDAC was
      associated with a significantly increased risk of fatal (P = .0033) and
      neurologic (P < .0001) toxicity. Among patients who achieved CR with SDAC,
      survival and disease-free survival (DFS) following consolidation randomization
      were not significantly better with HDAC compared with SDAC (P = .77 and .46,
      respectively). Patients who received both HDAC induction and consolidation had
      the best postremission outcomes; however, the proportion of CR patients who did
      not go on to protocol consolidation therapy was more than twice as high after
      HDAC induction compared with SDAC. Induction therapy with HDAC plus DNR was
      associated with greater toxicity than SDAC plus DNR, but with no improvement in
      CR rate or survival. Following CR induction with SDAC, consolidation with HDAC
      increased toxicity but not survival or DFS. In a nonrandomized comparison,
      patients who received both HDAC induction and consolidation had superior survival
      and DFS compared with those who received SDAC induction with either SDAC or HDAC
      consolidation.

PMID- 8874181
TI  - Evidence of both ontogeny and transplant dose-regulated expansion of
      hematopoietic stem cells in vivo.
AB  - Recent assessment of the long-term repopulating activity of defined subsets of
      hematopoietic cells has offered new insights into the characteristics of the
      transplantable stem cells of this system; however, as yet, there is very little
      known about mechanisms that regulate their self-renewal in vivo. We have now
      exploited the ability to quantitate these cells using the competitive
      repopulating unit (CRU) assay to identify the role of both intrinsic
      (ontological) and extrinsic (transplanted dose-related) variables that may
      contribute to the regulation of CRU recovery in vivo. Ly5.1 donor cells derived
      from day-14.5 fetal liver (FL) or the bone marrow (BM) of adult mice injected 4
      days previously with 5-fluorouracil were transplanted at doses estimated to
      contain 10, 100, or 1,000 long-term CRU into irradiated congenic Ly5.2 adult
      recipient mice. Eight to 12 months after transplantation, there was a complete
      recovery of BM cellularity and in vitro clonogenic progenitor numbers and a
      nearly full recovery of day-12 colony-forming unit-spleen numbers irrespective of
      the number or origin of cells initially transplanted. In contrast, regeneration
      of Ly5.1+ donor-derived CRU was incomplete in all cases and was dependent on both
      the origin and dose of the transplant, with FL being markedly superior to that of
      adult BM. As a result, the final recovery of the adult marrow CRU compartment
      ranged from 15% to 62% and from 1% to 18% of the normal value in recipients of FL
      and adult BM transplantation, respectively, with an accompanying maximum CRU
      amplification of 150-fold for recipients of FL cells and 15-fold for recipients
      of adult BM cells. Interestingly, the extent of CRU expansion from either source
      was inversely related to the number of CRU transplanted. These data suggest that
      recovery of mature blood cell production in vivo may activate negative feedback
      regulatory mechanisms to prematurely limit stem cell self-renewal ability.
      Proviral integration analysis of mice receiving retrovirally transduced BM cells
      confirmed regeneration of totipotent lymphomyeloid repopulating cells and
      provided evidence for a greater than 300-fold clonal amplification of a single
      transduced stem cell. These results highlight the differential regenerative
      capacities of CRU from fetal and adult sources that likely reflect intrinsic,
      genetically defined determinants of CRU expansion but whose contribution to the
      magnitude of stem cell amplification ultimately obtained in vivo is also strongly
      influenced by the initial number of CRU transplanted. Such findings set the stage
      for attempts to enhance CRU regeneration by administration of agents that may
      enable full expression of regenerative potential or through the expression of
      intracellular gene products that may alter intrinsic regenerative capacity.

PMID- 8874182
TI  - Thrombopoietin, but not erythropoietin promotes viability and inhibits apoptosis
      of multipotent murine hematopoietic progenitor cells in vitro.
AB  - The recently cloned c-mpl ligand, thrombopoietin (Tpo), has been extensively
      characterized with regard to its ability to stimulate the growth, development,
      and ploidy of megakaryocyte progenitor cells and platelet production in vitro and
      in vivo. Primitive hematopoietic progenitors have been shown to express c-mpl,
      the receptor for Tpo. In the present study, we show that Tpo efficiently promotes
      the viability of a subpopulation of Lin-Sca-1+ bone marrow progenitor cells. The
      ability of Tpo to maintain viable Lin-Sca-1+ progenitors was comparable to that
      of granulocyte colony-stimulating factor and interleukin-1, whereas stem cell
      factor (SCF) promoted the viability of a higher number of Lin-Sca-1+ progenitor
      cells when incubated for 40 hours. However, after prolonged (> 40 hours)
      preincubation, the viability-promoting effect of Tpo was similar to that of SCF.
      An increased number of progenitors surviving in response to Tpo had megakaryocyte
      potential (37%), although almost all of the progenitors produced other myeloid
      cell lineages as well, suggesting that Tpo acts to promote the viability of
      multipotent progenitors. The ability of Tpo to promote viability of Lin-Sca-1+
      progenitor cells was observed when cells were plated at a concentration of 1 cell
      per well in fetal calf serum-supplemented and serum-depleted medium. Finally, the
      DNA strand breakage elongation assay showed that Tpo inhibits apoptosis of Lin
      Sca-1+ bone marrow cells. Thus, Tpo has a potent ability to promote the viability
      and suppress apoptosis of primitive multipotent progenitor cells.

PMID- 8874183
TI  - In vitro expansion of hematopoietic progenitor cells induces functional
      expression of Fas antigen (CD95).
AB  - Fas antigen (Fas Ag; CD95) is a cell surface molecule that can mediate apoptosis.
      Bcl-2 is a cytoplasmic molecule that prolongs cellular survival by inhibiting
      apoptosis. To investigate the role of both molecules in hematopoiesis, we
      evaluated the expression of Fas Ag and Bcl-2 on CD34+ hematopoietic progenitor
      cells expanded in vitro. CD34+ cells isolated from bone marrow were cultured in
      iscove's modified Dulbecco's medium supplemented with 10% fetal calf serum, 1%
      bovine serum albumin, 50 ng/mL stem cell factor, 50 ng/mL interleukin-3 (IL-3),
      50 ng/mL IL-6, 100 ng/mL granulocyte colony-stimulating factor, and 3 U/mL
      erythropoietin for 7 days. Colony-forming unit of granulocytes/macrophages (CFU
      GM) and burst-forming unit of erythroids (BFU-E) were expanded 6.9-fold and 8.8
      fold in number at day 5 of culture, respectively. Freshly isolated CD34+ cells
      did not express Fas Ag, whereas approximately half of them expressed Bcl-2. CD34+
      cells cultured with hematopoietic growth factors gradually became positive for
      Fas Ag and rapidly lost Bcl-2 expression. Furthermore, apoptosis was induced in
      the cultured CD34+ population when anti-Fan antibody (IgM; 1 microgram/mL) was
      added, as shown by significant decrease in the number of viable cells,
      morphologic changes, induction of DNA fragmentation, and significant decrease in
      the number of clonogenic progenitor cells including CFU. GM and BFU-E. These
      results indicate that functional expression of Fas Ag is induced on CD34+ cells
      expanded in vitro in the presence of hematopoietic growth factors. Induction of
      Fas Ag and downregulation of Bcl-2 may be expressed as part of the
      differentiation program of hematopoietic cells and may be involved in the
      regulation of hematopoiesis.

PMID- 8874184
TI  - Dual action of retinoic acid on human embryonic/fetal hematopoiesis: blockade of
      primitive progenitor proliferation and shift from multipotent/erythroid/monocytic
      to granulocytic differentiation program.
AB  - In preliminary studies, we have analyzed the hematopoietic growth factor (HGF)
      requirement of hematopoietic progenitor cells (HPCs) purified from embryonic
      fetal liver (FL) and grown in fetal calf serum-supplemented (FCS+) clonogenic
      culture. The key role of erythropoietin (Epo) for colony formation by early
      erythroid progenitors (burst-forming units-erythroid [BFU-E]) has been confirmed.
      Furthermore, in the absence of exogenous HGFs, FL monocytic progenitors (colony
      forming unit monocyte [CFU-M]) generate large colonies exclusively composed of
      monocytes-macrophages; these colonies are absent in FCS- clonogenic culture. On
      this basis, we have investigated the role of all-trans retinoic acid (ATRA) and
      its isomer 9-cis RA in FL hematopoiesis. Both compounds modulate the growth of
      purified FL HPCs, which show a dose-dependent shift from mixed/erythroid/
      monocytic to granulocytic colony formation. Studies on unicellular and paired
      daughter cell culture unequivocally indicate that the shift is mediated by
      modulation of the HPC differentiation program to the granulopoietic pathway
      (rather than RA-induced down-modulation of multipotent/ erythroid/monocytic HPC
      growth coupled with recruitment of granulocytic HPCs). ATRA and 9-cis RA also
      exert their effect on the proliferation of primitive HPCs (high-proliferative
      potential colony-forming cells [HPP-CFCs]) and putative hematopoietic stem cells
      (HSCs; assayed in Dexter-type long-term culture). High concentrations of either
      compound (1) drastically reduced the number of primary HPP-CFC colonies and
      totally abolished their recloning capacity and (2) inhibited HSC proliferation.
      It is crucial that these results mirror recent observations indicating that
      murine adult HPCs transduced with dominant negative ATRA receptor (RAR) gene are
      immortalized and show a selective blockade of granulocytic differentiation.
      Altogether, these results suggest that ATRA/9-cis RA may play a key role in FL
      hematopoiesis via a dual effect hypothetically mediated by interaction with the
      RAR/RXR heterodimer, ie, inhibition of HSC/ primitive HPC proliferation and
      induction of CFU-GEMM/ BFU-E/CFU-M shift from the multipotent/erythroid/monocytic
      to the granulocytic-neutrophilic differentiation program.

PMID- 8874185
TI  - Increased granulocyte-macrophage colony-stimulating factor mRNA instability in
      cord versus adult mononuclear cells is translation-dependent and associated with
      increased levels of A + U-rich element binding factor.
AB  - The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA is
      fourfold lower in phorbol myristate acetate (PMA) + phytohemagglutinin (PHA)
      activated mononuclear cells (MNC) from newborns compared with adults. The GM-CSF
      transcription rate is similar in umbilical cord and adult MNC, but transcript
      half-life is threefold lower in cord activated MNC. Interaction of RNA binding
      proteins, such as the cloned adenosine + uridine-rich element, binding factor,
      AUF1, with eight AUUUA motifs in the human GM-CSF mRNA 3'-untranslated region (GM
      3'-UTR) has been implicated in regulating transcript stability. Translational
      inhibition by cycloheximide (CHX) significantly increased GM-CSF mRNA
      accumulation and half-life by three-fold in activated cord MNC, but had a minimal
      effect in activated adult MNC as compared with PMA + PHA alone. Electrophoretic
      mobility-shift assays with a 32P-labeled, 305-nucleotide RNA comprising the GM-3'
      UTR revealed two RNaseT1-resistant, bound complexes that were almost twice as
      abundant in cord than in adult MNC extracts. Mobility-shift competition assays
      and RNaseT1 mapping localized the binding site of both complexes to a 52
      nucleotide region containing seven of eight AUUUA motifs. Inclusion of AUF1
      antiserum produced a supershifted complex at 35-fold higher levels in cord than
      in adult MNC extracts. Extracts from the carcinoma cell line 5637, with extended
      GM-CSF mRNA half-life, also had very low levels of anti-AUF1 supershifted
      complex. Anti-AUF1 immunoblotting showed significantly higher levels of two AUF1
      protein isoforms and lower levels of one in cord than in adult MNC or 5637
      extracts. These results suggest that destabilization of GM-CSF mRNA in cord MNC
      is translation-dependent and that increased levels of specific AUF1 isoforms in
      cord MNC may target transcripts for increased degradation, which could account in
      part for dysregulation of neonatal phagocytic immunity.

PMID- 8874186
TI  - The effects of vitamin D binding protein-macrophage activating factor and colony
      stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats.
AB  - Osteopetrosis is a heterogeneous group of bone disorders characterized by the
      failure of osteoclasts to resorb bone and by several immunological defects
      including macrophage dysfunction. Two compounds, colony-stimulating factor-1 (CSF
      1) and vitamin D-binding protein-macrophage activating factor (DBP-MAF) were used
      in the present study to evaluate their effects on the peritoneal population of
      cells and on cells within the bone marrow microenvironment in normal and incisors
      absent (ia) osteopetrotic rats. Previous studies in this laboratory have
      demonstrated that administration of DBP-MAF to newborn ia animals results in a
      substantial increase in bone marrow cavity size due to upregulated osteoclast
      function. To study the effects of these compounds on the macrophage/osteoclast
      precursors, DBP-MAF, CSF-1, and the combination of these compounds were given to
      newborn ia and normal littermate animals. Both the normal and mutant phenotypes
      responded similarly when treated with these compounds. Rats exhibited a profound
      shift toward the macrophage lineage from the neutrophil lineage when compared
      with vehicle-treated control animals after treatment with these compounds. In the
      in vivo peritoneal lavage study, animals received injections of CSF-1, DBP-MAF or
      DBP-MAF/CSF-1 over a 4-week period. The various types of cells in the peritoneal
      cavity were then enumerated. The in vitro study consisted of cells isolated from
      the bone marrow microenvironment and cultured on feeder layers of CSF-1, DBP-MAF,
      or DBP-MAF/CSF-1 for colony enumeration. The increase in macrophage numbers at
      the expense of neutrophil numbers could be seen in both the in vivo and in vitro
      experiments. The macrophage/osteoclast and neutrophil lineages have a common
      precursor, the granulocyte/macrophage colony-forming cell (GM-CFC). With the
      addition of CSF-1, the GM-CFC precursor may be induced into the
      macrophage/osteoclast lineage rather than the granulocyte lineage. This increased
      pool of cells in the macrophage/osteoclast lineage can be functionally
      upregulated with the subsequent addition of DBP-MAF to perform the activities of
      phagocytosis and bone resorption. The in vitro data also showed that DBP-MAF did
      not support colony development as in CSF-1 or the combination treatment. The
      recruitment and activation of cells into the macrophage/ osteoclast lineage may
      help to correct the bone and immune defects found in diseases demonstrating a
      significant lack of myeloid cells, as well as neutrophilia disorders and the
      disease, osteopetrosis.

PMID- 8874187
TI  - Contribution of both STAT and SRF/TCF to c-fos promoter activation by granulocyte
      macrophage colony-stimulating factor.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic
      growth factor that has been shown to support call proliferation in murine
      fibroblasts engineered to stably express both chains of the human GM-CSF receptor
      (NIH-GMR). Because the proto-oncogene c-fos is believed to provide a link between
      short-term signals elicited at the membrane and long-term cellular response, we
      chose to study the mechanism of GM-CSF-dependent cell regulation using c-fos
      promoter activity as a molecular marker in both NIH-GMR transfectants and in the
      CD34+ cell line TF-1. The importance of c-fos and related AP-1 activity in GM-CSF
      signalling was suggested by a tight correlation between GM-CSF-dependent
      activation of the c-fos promoter and cell proliferation and by the inhibitory
      effect of a trans-dominant c-fos mutant on cell growth. To evaluate the
      contribution of the serum response factor (SRF) associated with the ternary
      complex factor (TCF) and of STAT proteins to c-fos promoter activation in
      response to GM-CSF, the SRF binding site (SRE) and/or the STAT binding site (SIE)
      were inactivated. In serum-free medium, both SRE and SIE are essential to c-fos
      promoter activation by GM-CSF in NIH-GMR transfectants and in TF-1 cells. No
      response to GM-CSF was observed when both sites were mutated. The nature of the
      STAT family member was further investigated by Wester blots and DNA retardation
      assays using an SIE probe. Our data indicate that GM-CSF induced DNA binding of
      both STAT1 and STAT3 in NIH-GMR and mainly of STAT3 in TF-1 cells. STAT5 tyrosine
      phosphorylation was also observed in TF-1 cells. Finally, expression of a
      dominant negative MAPK mutant, ERK192A, resulted in a decrease of both SRE- and
      SIE-dependent activation of c-fos promoter by GM-CSF, suggesting that STAT1/3 are
      regulated not only by tyrosine kinases, but also partially by MAPK.

PMID- 8874188
TI  - PU.1 but not ets-2 is essential for macrophage development from embryonic stem
      cells.
AB  - Transcription factors play an important role choreographing lineage commitment
      and expansion of blood cells. Nuclear factors that are expressed primarily or
      exclusively in hematopoietic cells are likely candidates for regulating blood
      cell development. The transcription factor PU.1 is found only in hematopoietic
      cells, whereas ets-2, a related family member, is ubiquitously expressed. To
      compare the role of these two transcription factors in macrophage development,
      embryonic stem (ES) cells with a homozygous disruption of either the PU.1 or the
      ets-2 gene were generated. The ability of both knockout ES cells to differentiate
      to macrophages was tested. Normal development of macrophages, as determined by
      histochemical and immunohistochemical analysis, from PU.1 knockout ES cells was
      significantly blocked. Furthermore, the expression of known markers associated
      with macrophages, such as c-fms, CD11b, CD18 and granulocyte-macrophage colony
      stimulating factor receptor, were not detected by reverse transcriptase
      polymerase chain reaction. In contrast to the PU.1 knockout ES cells,
      macrophages, development from the ets-2 knockout ES cells was normal. Although
      both PU.1 and ets-2 are found in macrophages, these data show a distinct role for
      the lineage-restricted PU.1 transcription factor in macrophage development.

PMID- 8874189
TI  - Local clonal analysis of the hematopoietic system shows that multiple small short
      living clones maintain life-long hematopoiesis in reconstituted mice.
AB  - We describe here a technique to study the clonal contribution of primitive stem
      cells that account for long-term hematopoiesis in the same mouse over a 14-month
      period. Specifically, irradiated recipient female mice were transplanted with
      retrovirally marked male hematopoietic progenitors. Bone marrow was then
      collected repeatedly from local sites from the same mice throughout a 14-month
      period and injected into secondary irradiated recipients for analysis of donor
      retrovirally marked day-11 colony-forming unit-spleen (CFU-S-11). We have tracked
      the temporal in vivo fate of 194 individual CFU-S-derived cell clones in 38 mice
      reconstituted with such retrovirally marked bone marrow cells. Our data show that
      long-term hematopoiesis is maintained by a large number of simultaneously
      functioning small, shortlived (1 to 3 months) clones that usually grow locally
      with little or no dispersion between different regions of the hematopoietic
      system. Furthermore, the clones that disappeared were never detected again. The
      data suggest that normal hematopoiesis is supported by the sequential recruitment
      of marrow repopulating cells into a differentiation mode.

PMID- 8874190
TI  - Shear-dependent changes in the three-dimensional structure of human von
      Willebrand factor.
AB  - The three-dimensional tertiary structure of human von Willebrand Factor (vWF) on
      a hydrophobic surface under aqueous conditions and different shear stress regimes
      was studied by atomic force microscopy (AFM). vWF was imaged by AFM at molecular
      level resolution under negligible shear stress, under a local applied shear force
      (7.4 to 19 nN) using the AFM probe in contact mode scanning, and after subjecting
      vWF to a range of shear stress (0 to 42.4 dyn/cm2) using a rotating disk system.
      The results demonstrate that vWF undergoes a shear stress-induced conformational
      transition from a globular state to an extended chain conformation with exposure
      of intra-molecular globular domains at a critical shear stress of 35 +/- 3.5
      dyn/cm2. The globular vWF conformation (149 nm by 77 nm and height 3.8 nm) is
      representative of native vWF after simple diffusion to the hydrophobic surface,
      followed by adhesion and some spreading. In a shear stress field above the
      critical value, protein unfolding occurs and vWF is observed in extended chain
      conformations oriented in the direction of the shear stress field with molecular
      lengths ranging from 146 to 774 nm and 3.4 nm mean height. The shear stress
      induced structural changes to vWF suggest a close conformation-function
      relationship in vWF properties for thrombogenesis in regions of high shear
      stress.

PMID- 8874191
TI  - Quantitative analysis of von Willebrand factor propeptide release in vivo: effect
      of experimental endotoxemia and administration of 1-deamino-8-D-arginine
      vasopressin in humans.
AB  - The results of studies with cultured endothelial cells have shown that most von
      Willebrand factor (vWF) synthesized is directly secreted (constitutive pathway)
      and consists of both mature vWF, its precursor molecule pro-vWF, and the cleaved
      vWF prosequence. Only fully processed, functionally mature vWF is stored within
      the cell, together with the propeptide, and leaves the cell only on stimulation
      (regulated secretion). Both in resting and stimulated cultured endothelial cells,
      the stoichiometry of the released propeptide to the released mature vWF is
      essentially equimolar. In the present study, we have measured the molar ratio of
      propeptide to mature vWF in vivo, both under resting conditions and conditions
      that reflect activation of the endothelium. To this end, we devised a method that
      allows the measurement of the propeptide (vW antigen II) on a quantitative, is,
      molar basis, using purified recombinant propeptide as a standard. Our results
      show that the molar concentration of the propeptide in normal plasma is about one
      tenth of the concentration of mature vWF (expressed as half-dimer concentration).
      This ratio is approximately 1:1 in the medium of cultured endothelial cells. On
      administration in healthy subjects of either 1-deamino-8-D-arginine vasopressin
      or endotoxin, both agents being known to elicit an intravascular increase of vWF,
      the molar ratio of propeptide to mature vWF increased fourfold to fivefold. The
      propeptide concentration returned to baseline values after about 6 to 7 hours of
      injection of each stimulus, whereas the increase of mature vWF was much more
      sustained. Because the respective half-lives of mature vWF and its propeptide
      clearly differ, measurement of the concentration of these proteins could provide
      a means to assess the extent of activation of the endothelium under physiological
      and pathophysiological conditions.

PMID- 8874192
TI  - Recipient humoral immunity against leukoreduced allogeneic platelets is
      suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide
      synthase.
AB  - Leukoreduced allogeneic platelet transfusions have been previously shown to
      initially stimulate an in vitro cellular cytotoxicity and subsequently Induce the
      formation of immunoglobulin G (IgG) antidonor alloantibodies. To further
      characterize these responses and determine if they are related, recipient BALB/c
      H-2d mice were treated with aminoguanidine (AMG), a selective inhibitor of
      inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 10(8)
      C57BL/6 H2b platelets. In control, non-AMG-treated mice, transfusion
      significantly (P < .01) increased serum levels of interferon-gamma (IFN-gamma) by
      day 1 posttransfusion (PT). IFN-gamma returned to pretransfusion levels by day 3
      PT, and its production was not affected by AMG treatment. Serum interleukin-4 (IL
      4), on the other hand, was undetectable before and during the transfusion
      protocol. By day 3 PT, recipient spleen cells could mediate in vitro anti-P815
      (auto), anti-EL4 (allo), and anti-R1.1 (third-party MHC) cytotoxicity, and these
      responses were maximal by day 7 PT. Concurrently, a significant reduction in the
      vitro ability of recipient splenocytes to respond to Concanavalin A (ConA) was
      observed; this was not seen with lipopolysaccharide (LPS) stimulation. Elevated
      levels of NO2- were found in the ConA culture supernatants from transfused mice
      at day 3 PT. Serum antidonor alloantibodies were detected by the fifth platelet
      transfusion. AMG treatment of recipient mice significantly inhibited the
      transfusion. Induced cytotoxicity and ConA-stimulated NO2- production, and
      restored ConA-induced proliferation to normal levels. AMG appeared to selectively
      inhibit platelet-induced alloantibody production in that it did not affect
      antibody production induced by transfusions with 10(5) allogeneic leukocytes or
      by immunization with a foreign protein antigen, human gamma globulin, in adjuvant
      therapy. These results indicate that an in vivo AMG-sensitive mechanism is
      essential for recipients to initiate a humoral IgG immune response against
      allogeneic platelets.

PMID- 8874193
TI  - Adhesion of platelets to surface-bound fibrinogen under flow.
AB  - After platelet activation, fibrinogen mediates platelet-platelet interactions
      leading to platelet aggregation. In addition, fibrinogen can also function as a
      cell adhesion molecule, providing a substratum for adhesion of platelets and
      endothelial cells. In this report, we studied the adhesion of platelets to
      surface-immobilized fibrinogen under flow in different shear rates. Heparinized
      whole blood containing mepacrine-labeled platelets was perfused for two minutes
      at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow
      chamber. The number of adherent fluorescent platelets was quantitated every 15
      seconds with an epifluorescent videomicroscope and digital image processing
      system. When compared with platelet adhesion and aggregation seen on glass
      surfaces coated with type I bovine collagen, a significant increase in platelet
      adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s
      1. The adherent platelets formed a single layer on fibrinogen-coated surfaces.
      Under identical conditions, no significant adhesion was observed on fibronectin-
      or vitronectin-coated surfaces. Although platelet adhesion to collagen was
      substantially inhibited by the platelet inhibitors prostaglandin E1 and
      theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen.
      Platelets adhered to recombinant homodimeric wild-type (gamma 400-411)
      fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen.
      Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at
      positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived
      fibrinogen. These results show that platelets adhere to fibrinogen-coated
      surfaces under moderate wall shear rates, that the interaction is mediated by the
      fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that
      the interaction is independent of platelet activation and the RGD sequences in
      the alpha chain.

PMID- 8874194
TI  - Inhibition of delayed-type contact hypersensitivity in mice deficient in both E
      selectin and P-selectin.
AB  - Leukocyte rolling and emigration in response to inflammatory stimuli appears to
      involve both E-selectin- and P-selectin-dependent adhesion, which suggests that
      these molecules have overlapping functions. To clarify their relative
      contributions in chronic inflammation, we examined delayed-type contact
      hypersensitivity (DTH) responses in P-selectin, E-selectin, and E-/P-selectin
      deficient mice. Oxazolone-induced increases in ear thickness and ear weight were
      equivalent in wild-type mice and in P-selectin and E-selectin mutants, but were
      significantly reduced in E-/P-selectin mutants. The number and area of
      microabscesses on the ears of E-/P-deficient mice were decreased by 72% and 93%,
      and the number of leukocytes invading the subdermal ear tissue was reduced. T
      cells from E-/P-deficient mice transferred oxazolone reactivity into naive wild
      type mice. However, when donor T cells from wild-type mice were transferred into
      E-/P-selectin-deficient mice, the DTH response was significantly impaired. These
      results show that leukocyte recruitment into a subacute inflammatory reaction can
      occur when either P-selectin or E-selectin is present, but is significantly
      reduced when both selectins are absent. Both P- and E-selectin are likely to play
      important roles in the development and maintenance of inflammatory diseases.

PMID- 8874195
TI  - Nitric oxide alters the expression of gamma-globin, H-ferritin, and transferrin
      receptor in human K562 cells at the posttranscriptional level.
AB  - Cellular iron metabolism is altered during chronic inflammatory states, leading
      to reticuloendothelial iron sequestration and an associated anemia. To study the
      effects of nitric oxide (NO) on the expression of three genes involved in
      erythroid cell iron metabolism (gamma-globin, H-ferritin, and transferrin
      receptor [TfR]), we developed a series of human K562 erythroleukemic cell clones
      retrovirally transduced with inducible nitric oxide synthase (NOS-2) and
      producing different steady-state levels of NO. gamma-Globin and H-ferritin
      protein expression was reduced in NO-producing cells in relation to the amount of
      NO produced. Conversely, cell surface TfR expression increased in NO-producing
      clones. Both the inhibitory effects of NO on gamma-globin and H-ferritin
      expression and the stimulatory effect on TfR were reversed by the NOS inhibitor
      NG-methyl-L-arginine (NGMMA). gamma-Globin and H-ferritin mRNA levels were
      unaffected by NO production. In the case of TfR, NO appeared to stabilize mRNA in
      that the half life of TfR mRNA decreased from approximately 15 hours to less than
      3 hours when NO production by NOS-transduced clones was inhibited. Thus, NO can
      regulate expression of these genes at the posttranscriptional level, an effect
      that is likely mediated by the known effect of NO on the RNA binding activity of
      iron regulatory protein-1 (Pantopoulos and Hentze, Proc Natl Acad Sci USA
      92:1267, 1995). Furthermore, our findings suggest a mechanism for the observed
      relationship between NO production and the pathophysiology of the anemia of
      chronic disease.

PMID- 8874196
TI  - Characterization of an inducible endothelial cell prothrombin activator.
AB  - In vivo prothrombin activation is thought to occur via a factor Xa/factor V
      dependent mechanism. We investigated whether human venous endothelial cells (EC)
      could be induced to express a prothrombin activator. EC treated with
      lipopolysaccharide (LPS) or interleukin-1 activated prothrombin in the absence of
      exogenous factors Xa and V. This activity resided in the membrane fraction of EC
      and was not inhibited by an antibody to factor V. The apparent Km value was 3.3
      +/- 0.3 mumol/L. Comparative studies of thrombin generation using a model system
      of phospholipid and factors Xa/V versus LPS-treated EC were performed to
      quantitate the effects of known inhibitors to factor Xa. The factor Xa inhibitor
      DEGR-chloromethyl ketone and an antibody to factor X inhibited prothrombin
      activation. However, the EC activator did not hydrolyze a factor Xa chromogenic
      substrate, and recombinant tick anticoagulant peptide did not suppress activity
      of the prothrombin activator. The apparent molecular weight of the EC activator
      was approximately 30 kD. Exogenous factor V enhanced the activity of the EC
      activator, such that in the presence of factor V, the apparent K(m) value was
      1.28 +/- 0.10 mumol/L. Additionally, LPS-treated EC activated exogenous factor V.
      This activator has several characteristics of a previously described inducible
      murine monocyte prothrombin activator and may contribute to thrombin generation
      associated with pathologic stimuli.

PMID- 8874197
TI  - Follicular dendritic cells adhere to fibronectin and laminin fibers via their
      respective receptors.
AB  - The expression of adhesion molecules on human tonsillar follicular dendritic
      cells (FDCs) in the secondary lymphoid follicle (LF) in vivo and in vitro was
      investigated using cryostat sections and cytospin preparations of FDCs isolated
      with a magnetic cell sorter, respectively. FDCs were immunochemically positive
      for Mac-1 (CD11b), sialyl-Lex (CD15s), CD22, integrin beta 1 (CD29), CD40, very
      late activation antigen (VLA)-alpha 3 (CD49c), VLA-alpha 5 (CD49e), VLA-alpha 6
      (CD49f), intercellular adhesion molecule (ICAM)-3 (CD50), ICAM-1 (CD54), B7
      (CD80), and vascular cell adhesion molecule (VCAM)-1 (CD106). With respect to
      ligands on B cells for these adhesion molecules, the CD11b-CD54, CD50-leukocyte
      function-associated molecule (LFA)-1 (CD11a/18), and CD106-VLA-4 (CD49d/29)
      interactions in the apical light (ALZ) and basal light (BLZ) zones; the CD15s-L
      selectin (CD62L) and CD106-CD49d/29 interactions in the mantle zone; and the CD54
      CD11a/18 interaction in the entire LF may participate in FDC-B cell adhesion.
      Namely, the adhesion molecules participating in FDC-B cell interactions may
      differ in each of the five zones. Furthermore, the immunochemical evidence that
      FDCs were fibronectin (VLA-5, CD49e/29) and laminin (VLA-6, CD49l/29) receptor
      positive discussed above was confirmed by immunoelectron microscopy and binding
      assays. Immunoelectron microscopy revealed fibers surrounded by cytoplasmic FDC
      extensions that were CD29-, CD49e-, and CD49f-positive. In the binding assays,
      the numbers of FDCs bound to fibronectin- and laminin-coated dishes and LFs of
      cryostat sections of human tonsils were reduced markedly by pretreatment with
      monoclonal antibodies against CD29, CD49e, and CD49f. These data indicate clearly
      that FDCs bind to reticulin and laminin fibers in LFs via their respective
      receptors.

PMID- 8874198
TI  - Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients
      with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for
      antibodies to the structural proteins of the virus.
AB  - Although most patients with the cutaneous T-cell lymphoma, mycosis fungoides
      (MF), are seronegative for human T-cell lymphotropic virus-I or -II (HTLV-I/II)
      when tested by assays that measure only antibodies to the viral structural
      proteins, the majority of such patients harbor HTLV-I-related pol and tax
      proviral sequences that encode proteins not included in routinely used serologic
      tests. Tax mRNA has also been detected in their peripheral blood mononuclear
      cells (PBMC). Therefore, it seemed possible that these patients have antibodies
      to the tax protein. To investigate this, enzyme-linked immunosorbent assays (ELI
      SAs) and Western blot assays were set up, using as antigens the full-length HTLV
      I tax cloned from the prototypic HTLV-I-infected cell line, C91PL, and from PBMC
      of a MF patient, as well as a synthetic peptide made to the carboxy-terminal 20
      amino acids of tax-I. Of 60 MF patients whose PBMC were shown to be positive for
      tax proviral DNA and mRNA, 50 (83%) were shown to have tax antibodies. The
      antigen derived from the MF patient was most useful in detecting such antibodies.
      These results demonstrate the need for including other HTLV-related antigens in
      addition to gag and env in serologic tests used to identify HTLV-infected
      individuals. The findings underscore the fact that individuals considered
      seronegative on the basis of currently used tests can be infected with HTLV.

PMID- 8874199
TI  - P-selectin glycoprotein ligand-1 is broadly expressed in cells of myeloid,
      lymphoid, and dendritic lineage and in some nonhematopoietic cells.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) is a muclin-like glycoportein ligand
      for P- and E-selectin on myeloid cells and a subset of lymphocytes. We used flow
      cytometry and immunohistochemistry to examine expression of PSGL-1 on minor
      leukocyte populations, differentiating hematopoletic cells, and nonhematopoietic
      tissues using two monoclonal antibodies to distinct protein epitopes on PSGL-1.
      In the bone marrow, PSGL-1 was expressed on myeloid cells from the myeloblast
      stage to the segmented neutrophil, but was not detected on erythroblasts or
      megakaryocytes. All types of circulating myeloid cells expressed PSGL-1, and PSGL
      1 was retained after extravasation of myetoid cells into tissues. PSGL-1 was also
      expressed on circulating dendritic cells, monocyte-derived dendritic cells,
      dendritic cells in lymphoid tissues and epidermis, and follicular dendritic
      cells. All types of lymphoid cells examined expressed PSGK-1, including immature
      and mature thymocytes, naive and memory T cells, gamma/delta T cells, netural
      killer cells, B cells and CD34+ progenitor cells. However, PSGL-1 levels were
      substantially lower on tonsillar lymphocytes than on circulating lymphocytes,
      suggesting that PSGL-1 expression is down regulated during or after entry of
      lymphocytes into secondary lymphoid tissue. Although PSGL-1 antigen was detected
      primarily on hamatopoietic cells, it was also present on time epithelium of the
      fallopian tube. Furthermore, PSGL-1 antigen gen was detected sporadically on
      microvascular endothelium in some pathologic tissues. This suggests that PSGL-1
      may have functions other than mediating leukocyte adhersion.

PMID- 8874200
TI  - Identification of an unusual Fc gamma receptor IIIa (CD16) on natural killer
      cells in a patient with recurrent infections.
AB  - We found an unusual fc gamma receptor IIIa (CD16) phenotype on the natural killer
      (NK) cells of a 3-year-old boy, who suffered from recurrent viral respiratory
      tract infections since birth. He also had severe clinical problems after Bacille
      Calmette-Geerin (BCG) vaccination and following Epstein-Barr virus and Varicella
      Zoster virus infections. His peripheral blood lymphocytes contained a normal
      percentage and absolute number of CD3-CD7+ cells, which were positively stained
      with the CD16 monoclonal antibodies (MoAbs) 3G8 and CLBFcRgran1, but did
      marginally stain with the CD16 MoAb Lau11c/B73.1. Fc gamma RillIb expression on
      granulocytes appeared to be normal. NK cell function, analyzed in vitro by direct
      cytotoxicity on K562 target cells and ADCC-activity on P815 target cells, was
      normal compared with an age-matched healthy control. Sequence analysis of the Fc
      gamma RIIIA gene, encoding CD16 on NK cells and macrophages, showed a T to A
      nucleotide substitution at position 230 on both alleles, predicting a leucine (L)
      to histidine (H) amino acid change position 48 in the first extracellular lg-like
      domain of Fc gamma RIIIa, which contains the Leu11c/B73.1 epitope. The combined
      use of CD16 and CD56 MoAbs labeled with the same fluorescent dye, as often
      applied in routine immunophenotyping procedures, will leave these homozygotes
      undiagnosed. The pattern of infections in this patient is in agreement with the
      postulated function of NK cells in the immunological defense against viruses and
      other intracellular microorganisms. Further analysis of the NK cell function in
      vitro and follow-up of the clinical course of Fc gamma RIIIA-48H/H homozygotes is
      required to ascertain whether this genotype is causally related to an NK cell
      immunodeficiency.

PMID- 8874201
TI  - Human blood basophils produce interleukin-13 in response to IgE-receptor
      dependent and -independent activation.
AB  - Interleukin-13 (IL-13) is a recently discovered immunoregulatory cytokine. The
      cellular sources of IL-13 and the regulation of its expression are largely
      unknown. Here we show that human basophils produce IL-13 in response to IgE
      receptor (IgER) crosslinking, IL-3, IL-3 plus C5a, but not C5a alone. Human
      basophils express IL-13 in a restricted manner since, apart from IL-4, no other
      cytokines encoded on the cytokine gene cluster (IL-3, IL-5, and granulocyte
      macrophage-colony-stimulating factor [GM-CSF]), are induced. Highest levels of IL
      13 are formed after IgE-independent activation leading to a prolonged secretion
      of IL-13. The response to IgER-cross-linking is more transient preferentially
      inducing IL-4, IL-3 is a unique cytokine regulating IL-13 production by human
      basophils: Among a large number of cytokines tested, only IL-3 is capable of
      directly inducing IL-13 expression. Furthermore, although some IL-13 is produced
      in response to C5a in the presence of IL-5, GM-CSF, IGF-1 or IL-1 beta, IL-3 is
      by far the most effective. IL-13 production was blocked by actinomycin D and
      cycloheximide and conditions leading to IL-13 release also lead to the induction
      of IL-13 mRNA. This study supports an important immunoregulatory role of human
      blood basophils, owing to their capacity to simultaneously express IL-13 and IL-4
      in a restricted manner.

PMID- 8874202
TI  - Inhibitory effect of a CD4-CDR3 peptide analog on graft-versus-host disease
      across a major histocompatibility complex-haploidentical barrier.
AB  - A structure-based designed peptide has been engineered to exhibit the same
      molecular surface as a portion of the CDR3-like region in domain 1 of the murine
      CD4 molecule. Earlier in vitro experiments indicated that this analog, known as
      rD-mPGPtide, inhibited T-cell proliferation in mixed lymphocyte reactions and
      blocked activation of both normal CD4+ T cells and T-cell lines after T-cell
      receptor triggering. In addition, rD-mPGPtide proved to be a potent inhibitor in
      vivo of CD4+ T-cell-mediated experimental allergic encephalomyelitis disease in
      the SJL mouse model. In this current report, we have evaluated the potential of
      rD-mPGPtide for suppressing the development of graft-versus-host disease (GVHD)
      in an irradiated major histocompatibility complex (MHC)-haploidentical murine
      bone marrow transplantation (BMT) model [(B6 x DBA/2)F1-->(B6 x CBA)F1 (950
      cGy)]. Our results indicated that early administration of rD-mPGPtide was
      effective in the inhibition of alloreactive responses of the donor T cells
      against the host and thus delayed or prevented the onset of GVHD. The median
      survival time of animals treated with rD-mPGPtide was enhanced as much as four
      fold with as little as a single dose of peptide at the time of transplant.
      Decreased alloreactivity was indicated by phenotypic and functional analysis of
      positively selected thoracic duct lymphocytes 4 days after transplant and by
      histopathological examination of skin and gastrointestinal tissue samples 4 weeks
      later. Therefore, the administration of a CD4-CDR3 peptide is an efficacious
      approach against the development of GVHD during allogeneic BMT.

PMID- 8874203
TI  - Human T lymphocytes and hematopoietic cell lines express CD24-associated
      carbohydrate epitopes in the absence of CD24 mRNA or protein.
AB  - The CD24 surface antigen is a small glycophosphatidylinositol (GPI)-anchored
      glycoprotein found on human granulocytes and most B lymphocytes. Many CD24
      monoclonal antibodies (MoAbs) have been described that identify several epitopes,
      with the majority of them related to carbohydrate structures associated with the
      CD24 molecule. Considerable variation has been observed in the apparent tissue
      distribution of the CD24 antigen depending on the MoAb used, and hence the CD24
      epitope studied. In this study, CD24 expression by human cell lines and normal
      hematopoietic call populations was assessed using a panel of carbohydrate and
      protein core-specific CD24 MoAbs and reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis. A number of CD24 carbohydrate epitope-reactive MoAbs
      bound to both T lymphocytes and several hematopoietic cell lines, despite the
      absence of concomitant CD24 mRNA or detectable surface CD24 core protein in the
      same cells. This additional CD24 MoAb reactivity on T lymphocytes was, in common
      with that observed on granulocytes (CD24 protein+), specifically inhibited by the
      presence of both sialyllactose and mucin. Similarly, the binding of carbohydrate
      epitops-reactive CD24 MoAb was reduced on both T lymphocytes and granulocytes by
      pretreatment with phospholipase C, pronase, or neuraminidase. Together, the data
      indicate that a number of CD24-associated carbohydrate epitopes have a broader
      tissue distribution than the CD24 protein and are expressed on additional GPI
      linked molecule(s). These findings have immediate implications for both leukemia
      phenotyping and attempts to examine CD24 function with CD24 MoAb.

PMID- 8874204
TI  - Modulation of in vitro and in vivo T-cell responses by transferrin-gallium and
      gallium nitrate.
AB  - Gallium is a group IIIa metal that has efficacy in the therapy of malignant
      disorders such as lymphoma and urothelial tract tumors. Preclinical studies also
      indicate a role for gallium in autoimmune disorders, suggesting that gallium is
      able to modulate T-cell immune reactivity. The purpose of this study was to
      examine the in vitro and in vivo immunomodulatory action of gallium on T-cell
      function. Since gallium binds to transferrin in vivo, in vitro studies evaluated
      the effect of transferrin-gallium (Tf-Ga) on human T cells. Tf-Ga inhibited the
      mitogen-induced proliferative response of peripheral blood mononuclear cells
      (PBMC) in a dose-dependent fashion. Alloantigen-induced proliferation was also
      potently suppressed when evaluated in a mixed lymphocyte culture assay. Tf-Ga
      affected a significant reduction in the density of IL-2 receptors on activated T
      cells and a slight reduction in the number of CD3+/CD25+ T cells in PHA
      stimulated cultures. Neither secretion of interleukin-2 (IL-2) nor the induction
      of IL-2-stimulated lymphokine-activated killer activity, however, was inhibited
      by Tf-Ga. Tf-Ga produced significant upregulation of the transferrin receptor
      (CD71) in T cells as determined by flow cytometric analysis and northern blot
      assay, but did not affect the percentage of CD3+/ CD71+ T cells after mitogen
      stimulation. To assess the in vivo effects of gallium on alloreactive T cells, we
      evaluated the immunosuppressive effect of gallium in a murine model of graft
      versus-host disease (GVHD). Administration of gallium significantly prolonged
      survival in mice undergoing severe GVHD, suggesting that gallium can ameliorate
      GVH reactivity. Collectively, these data demonstrate that, at clinically
      achievable concentrations, Tf-Ga potently inhibits T-cell activation and that
      this immunosuppressive property of gallium may be of adjunctive therapeutic value
      in the management of disorders characterized by the presence of autoreactive or
      alloreactive T-cell populations.

PMID- 8874205
TI  - Two types of defective human T-lymphotropic virus type I provirus in adult T-cell
      leukemia.
AB  - Adult T-cell leukemia (ATL), an aggressive neoplasm of mature helper T cells, is
      etiologically linked with human T lymphotropic virus type I (HTLV-1). After
      infection, HTLV-I randomly integrates its provirus into chromosomal DNA. Since
      ATL is the clonal proliferation of HTLV-I-infected T lymphocytes, molecular
      methods facilitate the detection of clonal integration of HTLV-I provirus in ATL
      cells. Using Southern blot analyses and long polymerase chain reaction (PCR) we
      examined HTLV-I provirus in 72 cases of ATL, of various clinical subtypes.
      Southern blot analyses revealed that ATL cells in 18 cases had only one long
      terminal repeat (LTR). Long PCR with LTR primers showed bands shorter than for
      the complete virus (7.7 kb) or no bands in ATL cells with defective virus. Thus,
      defective virus was evident in 40 of 72 cases (56%). Two types of defective virus
      were identified: the first type (type 1) defective virus retained both LTRs and
      lacked internal sequences, which were mainly the 5' region of provirus, such as
      gag and pol. Type 1 defective virus was found in 43% of all defective viruses.
      The second form (type 2) of defective virus had only one LTR, and 5'-LTR was
      preferentially deleted. This type of defective virus was more frequently detected
      in cases of acute and lymphoma-type ATL (21/54 cases) than in the chronic type
      (1/18 cases). The high frequency of this defective virus in the aggressive form
      of ATL suggests that it may be caused by the genetic instability of HTLV-I
      provirus, and cells with this defective virus are selected because they escape
      from immune surveillance systems.

PMID- 8874206
TI  - The biologic properties of recombinant human thrombopoietin in the proliferation
      and megakaryocytic differentiation of acute myeloblastic leukemia cells.
AB  - Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and
      thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic
      leukemia (AML) cells are largely unknown. To determine if recombinant human (rh)
      TPO has proliferation-supporting and differentiation-inducing activities in AML
      cells, 15 cases of AML cells that were exclusively composed of undifferentiated
      leukemia cells and showed growth response to rhTPO in a short-term culture (72
      hours) were subjected to long-term suspension culture with or without rhTPO. Of
      15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases
      whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In
      addition to the proliferation-supporting activity, rhTPO was found to induce AML
      cells to progress to some degree of megakaryocytic differentiation at both
      morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes.
      The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation
      of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the
      expression of erythroid/megakaryocyte-specific transcription factors (GATA-1,
      GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that
      showed megakaryocytic differentiation in response to rhTPO. These results
      suggested that, at least in a fraction of AML cases, TPO could not only support
      the proliferation of AML cells irrespective of AML subtypes, but could also
      induce megakaryocytic differentiation, possibly through activation of GATA-1,
      GATA-2, and NF-E2.

PMID- 8874207
TI  - Frequent deletion in the methylthioadenosine phosphorylase gene in T-cell acute
      lymphoblastic leukemia: strategies for enzyme-targeted therapy.
AB  - Methylthioadenosine phosphorylase (MTAP), an enzyme essential for the salvage of
      adenine and methionine, is deficient in a variety of cancers, including acute
      lymphoblastic leukemia (ALL). Because the MTAP gene is located adjacent to the
      tumor-suppressor gene p16 on chromosome 9p21 and more than 60% of T-cell ALL (T
      ALL) patients have deletion in the p16 gene, we examined the status of the MTAP
      gene in T-ALL patients. Quantitative polymerase chain reaction amplification of
      exon 8 of MTAP showed a deletion in 16 of 48 (33.3%) patients at diagnosis and in
      13 of 33 (39.4%) patients at relapse. Southern blot analysis showed that, in
      addition to deletion of the entire MTAP gene, a common break point was between
      exons 4 and 5, resulting in deletion of exons 5 through 8. The finding of
      frequent deficiency of MTAP in T-ALL offers the possibility of an enzyme targeted
      therapy for T-ALL. MTAP(-) T-ALL-derived cell line, CEM cells were very sensitive
      to methionine deprivation, with cell viability at 50% of control as early as 48
      hours after methionine deprivation. In contrast, methionine deprivation had
      little effect on the viability of normal lymphocytes or on their proliferative
      response to phytohemagglutinin. Alanosine, an inhibitor of AMP synthesis,
      inhibited the growth of both MTAP(+) (Molt-4 and Molt-16) and MTAP(-) (CEM and
      HSB2) cell lines. However, the addition of methylthioadenosine, the substrate of
      MTAP, protected the MTAP(+) cells but not the MTAP(-) cells from alanosine
      toxicity. These findings suggest the possibility of targeting MTAP for selective
      therapy of T-ALL.

PMID- 8874208
TI  - Selection of myeloid progenitors lacking BCR/ABL mRNA in chronic myelogenous
      leukemia patients after in vitro treatment with the tyrosine kinase inhibitor
      genistein.
AB  - Chronic myelogenous leukemia (CML) is a clonal disorder of the hematopoietic stem
      cell characterized by a chimeric BCR/ABL gene giving rise to a 210-kD fusion
      protein with dysregulated tyrosine kinase activity. We investigated the effect of
      genistein, a protein tyrosine kinase inhibitor, on the in vitro growth of CML and
      normal marrow-derived multi-potent (colony-forming unit-mix [CFU-Mix]), erythroid
      (burst-forming unit-erythroid [BFU-E]), and granulocyte-macrophage (colony
      forming unit-granulocyte-macrophage [CFU-GM]) hematopoietic progenitors.
      Continuous exposure of CML and normal marrow to genistein induced a statistically
      significant and dose-dependent suppression of colony formation. Genistein doses
      causing 50% inhibition of CML and normal progenitors were not significantly
      different for CFU-Mix (27 mumol/L v 23 mumol/L), BFU-E (31 mumol/L v 29 mumol/L),
      and CFU-GM (40 mumol/L v 32 mumol/L v 32 mumol/L). Preincubation of CML and
      normal marrow with genistein (200 mumol/ L for 1 to 18 hours) induced a time
      dependent suppression of progenitor cell growth, while sparing a substantial
      proportion of long-term culture-initiating cells (LTC-IC) from CML (range, 91% +/
      9% to 32% +/- 3%) and normal marrow (range, 85% +/- 8% to 38% +/- 9%). Analysis
      of individual CML colonies for the presence of the hybrid BCR/ABL mRNA by reverse
      transcription-polymerase chain reaction (RT-PCR) showed that genistein treatment
      significantly reduced the mean +/- SD percentage of marrow BCR/ABL+ progenitors
      both by continuous exposure (76% +/- 18% v 24% +/- 12%, P < or = .004) or
      preincubation (75% +/- 16% v 21% +/- 10%, P < or = .002) experiments.
      Preincubation with genistein reduced the percentage of leukemic LTC-IC from 87%
      +/- 12% to 37% +/- 12% (P < or = .003). Analysis of individual colonies by
      cytogenetics and RT-PCR confirmed that genistein-induced increase in the
      percentage of nonleukemic progenitors was not due to suppression of BCR/ABL
      transcription. Analysis of nuclear DNA fragmentation by DNA gel electrophoresis
      and terminal deoxynucleotidyl transferase assay showed that preincubation of CML
      mononuclear and CD34+ cells with genistein induced significant evidence of
      apoptosis. These observations show that genistein is capable of (1) exerting a
      strong antiproliferative effect on CFU-Mix, BFU-E, and CFU-GM while sparing the
      more primitive LTC-IC and (2) selecting benign hematopoietic progenitors from CML
      marrow, probably through an apoptotic mechanism.

PMID- 8874209
TI  - Different CD44 splicing patterns define prognostic subgroups in multiple myeloma.
AB  - CD44 variant isoforms (CD44v) are generated by alternative splicing of the
      nuclear RNA resulting in the expression of additional protein domains in the
      extracellular region of the CD44 standard molecule (CD44s). In multiple myeloma
      (MM), CD44 mediates binding of tumor cells to stroma and regulates interleukin-6
      production. To evaluate the role of CD44v isoforms in MM, CD44v expression was
      analyzed by immunohistochemical staining of 64 bone marrow biopsies from 38 MM
      patients. Expression of variant isoforms containing the 9v domain was observed in
      36% of cases and was associated with an advanced stage (P < .02; n = 61), a
      progressive disease (P < .001; n = 61), and a shorter overall survival (P < .02;
      n = 36). In contrast, 3v, 4v, 6v, or 10v isoforms were detected only in a small
      percentage of the patients. To analyze the exon composition in RNA-transcripts,
      reverse transcriptase polymerase chain reaction analyses followed by Southern
      hybridization with exon-specific probes were performed in fluorescence-activated
      cell sorted myeloma plasma cells. Tumors expressing the 9v domain showed complex,
      9v-containing transcripts in combinations with the 3v, 7v, 8v, and 10v exons.
      Identical transcripts were detected in several myeloma cell lines and in a Ki-1 B
      immunoblastic lymphoma. Similar to high-grade non-Hodgkin's lymphoma and gastric
      and renal cell carcinoma, overexpression of 9v-containing isoforms in MM is
      related to an unfavorable clinical presentation and represents a new prognostic
      parameter.

PMID- 8874210
TI  - Minimal region of loss at 13q14 in B-cell chronic lymphocytic leukemia.
AB  - Allelic loss at nonrandom chromosomal sites is thought to mark the position of
      tumor suppressor genes involved in the pathogenesis and progression of human
      malignancies. Solid tumors in particular have been found to harbor multiple
      genetic changes resulting in loss of function mutations. Tumor suppressor genes
      have also been found to be involved in the progression of lymphoid tumors.
      Previous reports have suggested the involvement of a tumor suppressor gene
      located on the long arm of chromosome 13, between the retinoblastoma (RB) and
      D13S25 loci, in the pathogenesis and or progression of more than 40% of B-cell
      chronic lymphocytic leukemia (B-CLL), a common lymphoid malignancy whose
      molecular etiology remains largely unknown. In the present study, we report the
      construction and characterization of a YAC contig spanning a region of
      approximately 3 cM between the RB gene and the D13S31 locus. We also screened 60
      paired normal/tumor B-CLL samples for allelic loss on chromosome 13 with nine
      microsatellite markers located between RB and D13S25. This analysis has allowed
      us to narrow the smallest region of loss to a segment of 550 kb located between
      the 206XF12 and D13S25 markers.

PMID- 8874211
TI  - Expression of pertussis toxin adenosine diphosphate-ribosyltransferase in a T
      cell hybridoma reduces metastatic capacity.
AB  - T-cell hybridomas are highly metastatic, and their in vitro invasiveness
      correlates with metastatic capacity. Invasion is blocked by pertussis toxin (PT),
      which adenosine diphosphate (ADP)-ribosylates G1-proteins, and we have provided
      evidence that the PT-sensitive signal stimulates leukocyte function-associated
      antigen-1 (LFA-1)-mediated adhesion required for invasion. PT pretreatment of
      TAM2D2 T-cell hybridoma cells reduced metastasis, but only to a limited extent.
      In the present study, we have transfected the cDNA of the PT ADP
      ribosyltransferase S1 subunit into TAM2D2 cells to abrogate G1-protein function
      permanently. We report here a substantial reduction in the metastatic capacity of
      two transfectants, S05 and S09, in which 88% and 95% of the G1-proteins was ADP
      ribosylated. Two-thirds of the mice injected with S09 cells were tumor-free.
      Metastasis to the liver was almost completely prevented and less metastases were
      formed in the spleen and kidneys. Metastasis formation by S05 cells in liver and
      spleen was much reduced, but in lymph nodes and peritoneal tissues, metastases
      occurred with a frequency similar to that of controls. We conclude that G1
      proteins play an important role in T-cell hybridoma metastasis. We propose that
      the reduction in metastasis is due to diminished entry of tumor cells from the
      blood into tissues.

PMID- 8874212
TI  - Primary effusion lymphoma in women: report of two cases of Kaposi's sarcoma
      herpes virus-associated effusion-based lymphoma in human immunodeficiency virus
      negative women.
AB  - Recent molecular evidence suggests an association with a new herpes virus,
      Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8), and primary effusion
      lymphomas (PEL). PELs have a characteristic morphology, phenotype, and clinical
      presentation with malignant effusions in the absence of a contiguous solid tumor
      mass. Most cases of PEL have occurred in human immunodeficiency virus (HIV)
      positive male patients who are coinfected with Epstein-Barr virus (EBV). This
      report describes two cases of PEL in HIV- and EBV-negative women. In one patient,
      a pleural cavity PEL was preceded by classic Kaposi's Sarcoma (KS) of the lower
      extremities. In the second patient, PEL developed in an artificial cavity related
      to the capsule of a breast implant. Both cases had the characteristic morphologic
      appearance of high-grade anaplastic/B-cell immunoblastic lymphomas, with loss of
      B-cell differentiation antigens, clonal immunoglobulin heavy chain gene
      rearrangements, and expression of activation antigen CD30. Both cases were
      negative for EBV, herpes virus simplex, and cytomegalovirus (CMV). DNA extracted
      from both lymphomas and skin KS specimen showed KSHV sequences by molecular
      analysis. This report expands the spectrum of KSHV-associated disease to include
      PEL in HIV-negative women.

PMID- 8874213
TI  - CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's
      lymphoma and Hodgkin's disease.
AB  - The Epstein-Barr virus (EBV) latency C promoter drives expression of a family of
      viral proteins commonly targeted by CD8 cytotoxic T cells. These proteins are not
      generally expressed in African Burkitt's lymphoma and in EBV-associated Hodgkin's
      disease. The failure to express these proteins is almost certainly an important
      factor in the evasion of immunosurveillance by EBV-associated tumors. In a
      previous study, we have shown that transcriptional activation of the C promoter
      is inhibited by methylation of a particular CpG site upstream of the promoter
      that prevents binding of a cellular protein (CBF2), and we have shown that this
      and adjacent CpG sites are methylated in a Burkitt's lymphoma cell line. In the
      present study, we show that CpG sites in the CBF2 binding region are
      predominantly methylated in African Burkitt's lymphoma and in EBV-associated
      Hodgkin's disease. In addition, we present the first direct evidence that the C
      promoter is transcriptionally silent in Burkitt's lymphoma. In contrast, we show
      a complete absence of methylation in the CBF2 binding region in a case of
      reversible EBV-associated B-cell lymphoma arising in an immunocompromised patient
      whose tumor shows C promoter transcriptional activity. By inhibiting expression
      of highly antigenic viral proteins, methylation of transcriptional control
      sequences may veil the presence of virus in tumor tissue from CD8(+) cytotoxic T
      cell immune surveillance and thus facilitate viral tumorigenesis.

PMID- 8874214
TI  - Growth pattern and clinical correlation of subcutaneously inoculated human
      primary acute leukemias in severe combined immunodeficiency mice.
AB  - We examined the ability of patient-derived human leukemic blasts to generate
      leukemic growth and dissemination in severe combined immunodeficiency (SCID) mice
      by subcutaneous inoculation without conditioning treatment or administration of
      growth-promoting cytokines. Additionally, we correlated the growth pattern with
      the clinical outcome of patients from whom the leukemic cells were derived. The
      leukemias displayed three distinct growth patterns, ie, either aggressive,
      indolent, or no tumor growth. Leukemic cells from 6 of 13 patients with acute
      myeloid leukemia (AML), 4 of 7 T-cell acute lymphoblastic leukemia (T-ALL), and
      11 of 16 patients with B-lineage ALL grew as subcutaneous tumors, with a
      significant number subsequently disseminating into distant organs in SCID mice.
      Patients whose leukemic blasts displayed an aggressive growth and dissemination
      pattern in SCID mice had a relatively poor clinical outcome, whereas patients
      with AML and T- or B-lineage ALL whose leukemic blasts grew indolently or whose
      cells failed to induce growth had a more favorable clinical course. Our study has
      shown that the subcutaneous inoculation of patient-derived human leukemic cells
      in SCID mice can engraft and grow as subcutaneous tumors with subsequent
      dissemination to distant organs in a manner analogous to their pattern of growth
      in humans. Additionally, these data suggest a clinical correlation to the growth
      and dissemination of some leukemic subtypes that may represent not only an
      additional prognosticator for patient outcome, but also a vehicle for the study
      of the biologic behavior of human leukemias and the development of novel
      therapeutic strategies.

PMID- 8874215
TI  - Retinoids irreversibly inhibit in vitro growth of Epstein-Barr virus-immortalized
      B lymphocytes.
AB  - Natural and synthetic retinoids have proved to be effective in the treatment and
      prevention of various human cancers. In the present study, we investigated the
      effect of retinoids on Epstein-Barr virus (EBV)-infected lymphoblastoid cell
      lines (LCLs), since these cells closely resemble those that give rise to EBV
      related lymphoproliferative disorders in the immunosuppressed host. All six
      compounds tested inhibited LCL proliferation with no significant direct
      cytotoxicity, but 9-cis-retinoic acid (RA), 13-cis-RA, and all-trans-RA (ATRA)
      were markedly more efficacious than Ro40-8757, Ro13-6298, and etretinate. The
      antiproliferative action of the three most effective compounds was confirmed in a
      large panel of LCLs, thus appearing as a generalized phenomenon in these cells.
      LCL growth was irreversibly inhibited even after 2 days of treatment at drug
      concentrations corresponding to therapeutically achievable plasma levels.
      Retinoid-treated cells showed a marked downregulation of CD71 and a decreased S
      phase compartment with a parallel accumulation in Gzero/ G1 phases. These cell
      cycle perturbations were associated with the upregulation of p27 Kip1, a nuclear
      protein that controls entrance and progression through the cell cycle by
      inhibiting several cyclin/cyclin-dependent kinase complexes. Unlike what is
      observed in other systems, the antiproliferative effect exerted by retinoids on
      LCLs was not due to the acquisition of a terminally differentiated status. In
      fact, retinoid-induced modifications of cell morphology, phenotype
      (downregulation of CD19, HLA-DR, and s-Ig, and increased expression of CD38 and c
      Ig), and IgM production were late events, highly heterogeneous, and often
      slightly relevant, being therefore only partially indicative of a drug-related
      differentiative process. Moreover, EBV-encoded EBV nuclear antigen-2 and latent
      membrane protein-1 proteins were inconstantly downregulated by retinoids,
      indicating that their growth-inhibitory effect is not mediated by a direct
      modulation of viral latent antigen expression. The strong antiproliferative
      activity exerted by retinoids in our experimental model indicates that these
      compounds may represent a useful tool in the medical management of EBV-related
      lymphoproliferative disorders of immunosuppressed patients.

PMID- 8874216
TI  - Epstein-Barr virus and familial Hodgkin's disease.
AB  - Several studies suggest that the Epstein-Barr virus (EBV) is etiologically linked
      to Hodgkin's disease (HD). This study was undertaken to examine the role of EBV
      in familial HD (FHD). Among 60 FHD patients from 27 families with two or more
      cases per family, we tested available paraffinized tumor tissues from 46 cases by
      in situ hybridization for EBV-encoded RNA (EBER1) expression. Thirteen of 46 FHD
      patients (28%) had EBER1 expressed in the Reed-Sternberg cells. Concordance rate
      of EBV positivity was evaluated among 34 first-degree related pairs from 17
      families for which both cases had available paraffinized tumor tissues. Only two
      of 17 pairs were concordant for EBER1 positivity. There was no excess of positive
      concordance (P = .18). Serologically, FHD patients had higher geometric mean
      antibody titers (GMTs) to the viral capsid antigen (VCA) and early antigen D (EA
      D). There was no difference in seroprevalence between patients and control
      groups, nor was there concordance in elevated serology among 15 pairs of first
      degree related FHD cases. Young adult unaffected family members (UFM) may not
      react to EBV in the same way as the general population as evidenced by the lower
      titer of VCA, although not statistically significant, and significantly lower
      titers of EA-D, compared with age-matched controls. While EBV might have some
      role in a subset of HD, lack of concordance of EBER1 expression and EBV serology
      among the FHD cases in the same family suggest that EBV does not play an
      important role in FHD.

PMID- 8874217
TI  - Fate of contaminating t(14; 18)+ lymphoma cells during ex vivo expansion of CD34
      selected hematopoietic progenitor cells.
AB  - The use of ex vivo expanded CD34-selected hematopoietic progenitor cells (HPCs)
      for autologous stem cell support or gene therapy is a major area of research and
      is likely to increase in the future. At present, little is known about the fate
      of contaminating malignant cells during ex vivo expansion of CD34-selected HPCs.
      We established a competitive polymerase chain reaction (PCR) titration assay to
      determine the number of residual lymphoma cells before and after selection and ex
      vivo expansion of CD34-selected HPCs in patients with t(14; 18) translocation
      carrying non-Hodgkin's lymphoma. Seven bone marrow (BM) and 2 mobilized
      peripheral blood progenitor cell samples from 8 patients without histologic BM
      involvement at the time of the harvest were analyzed by competitive PCR titration
      assay and determined to contain between < or = 10 and 4,000 lymphoma cells/ 10(6)
      mononuclear cells (MNCs). Immunoadsorption enriched CD34+ cells from a mean of 5%
      (range, 1% to 9%) to a mean of 88% (range, 76% to 94%) of MNCs and resulted in a
      1 to 4 log depletion of contaminating tumor cells. Two HPC samples became PCR
      negative after CD34 selection, whereas 7 samples still contained < or = 10 to 200
      residual lymphoma cells/10(5) MNCs. CD34-selected cells were consecutively
      expanded in suspension culture in the presence of stem cell factor, interleukin-1
      beta (IL-1 beta), IL-3, and IL-6. The mean increase of cells was 13-fold (range,
      4- to 22-fold) at day 7 and 65-fold (range, 43- to 110-fold) at day 14 of
      culture. Expansion resulted predominantly in myelomonocytic differentiation,
      whereas B-cell antigen-expressing cells became undetectable. Six of the seven PCR
      positive CD34-selected samples became PCR-negative for the t(14; 18)
      translocation at day 7 and/or 14 of expansion. One PCR-positive and one PCR
      negative CD34-selected sample were PCR-positive after ex vivo expansion, but the
      number of residual lymphoma cells remained at the limit of detection. We conclude
      that CD34-selection does not eliminate contaminating lymphoma cells in the
      majority of t(14; 18)+ HPC harvests. However, during ex vivo expansion of CD34
      selected HPCs, residual t(14; 18)+ lymphoma cells do not proliferate and become
      undetectable by PCR in the majority of cases.

PMID- 8874218
TI  - Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils:
      modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and
      apoptosis by IL-15.
AB  - Human neutrophils have been shown recently to express both the beta and the gamma
      chains of the interleukin-2 receptor (IL-2R). IL-15, a cytokine that has recently
      been cloned and characterized, was found to share many of the biological
      functions of IL-2 and is known to mediate signals through IL-2R beta and IL-2R
      gamma. In recent studies, we observed that IL-2 exerts few effects on various
      neutrophil functions, but information on IL-15-neutrophil interactions is
      lacking. In this study, we observed that IL-15, in contrast to IL-2, induces
      important morphological cell shape changes that are typical of activated
      neutrophils. Furthermore, phagocytosis of opsonized sheep red blood cells was
      significantly increased by IL-15 but not by IL-2. However, similar to IL-2, IL-15
      did not modulate the oxidative burst response. Furthermore, we observed that de
      novo RNA synthesis is increased in neutrophils by IL-15 along with de novo
      protein synthesis, whereas no significant effect of IL-2 was noted. Among the
      different proteins that were found to be upregulated by IL-15, one was identified
      by microsequencing as the cytoskeletal protein actin. Finally, we found that IL
      15 delays apoptosis of neutrophils more efficiently than IL-2 when evaluated by
      both microscopic observations and flow cytometry procedures. Furthermore, this
      phenomenon was dose-dependent (10 to 500 ng/mL), and, at 500 ng/mL, IL-15 delayed
      apoptosis as strongly as granulocyte-macrophage colony-stimulating factor. This
      study is the first to show that IL-15 is a significant neutrophil agonist.
      Moreover, in view of the differential effects of IL-15 and IL-2 on this cell
      type, our results support the existence of a specific IL-15R component(s) on
      human neutrophils.

PMID- 8874219
TI  - Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on
      monocytic cells.
AB  - The leukocyte integrin Mac-1 (CD11b/CD18) and the urokinase receptor (uPAR, CD87)
      mediate complementary functions in myelomonocytic cells. Both receptors promote
      degradation of fibrin(ogen) and also confer adhesive properties on cells because
      Mac-1 and uPAR bind fibrin and vitronectin, respectively. Staining of lung biopsy
      specimens from patients with acute lung injury indicated that fibrin and
      vitronectin colocalize at exudative sites in which macrophages bearing these
      receptors accumulate. Because of the parallel roles and physical proximity of Mac
      1 and uPAR, the capacity of these receptors to functionally interact was
      explored. Induction of Mac-1 and uPAR expression on monocytic cell lines by
      transforming growth factor- beta 1 and 1.25-(OH)2 vitamin D3 conferred urokinase
      and uPAR-dependent adhesion to vitronectin, which was further promoted by
      engagement of Mac-1. Vitronectin attachment promoted subsequent Mac-1-mediated
      fibrinogen degradation threefold to fourfold. In contrast, enhancement of uPAR
      occupancy by exogenous urokinase or receptor binding fragments thereof inhibited
      Mac-1 function. Addition of urokinase progressively inhibited Mac-1-mediated
      fibrinogen binding and degradation (maximal inhibition, 91% +/- 14% and 72% +/-
      15%, respectively). Saturation of uPAR with urokinase also inhibited binding of
      the procoagulant Mac-1 ligand, Factor X. These inhibitory effects of uPAR were
      reproduced in fresh monocytes, cultured monocytic cells, and in Chinese hamster
      ovary (CHO) cells transfected with both human Mac-1 and human uPAR. These data
      show that the procoagulant and fibrinolytic potential of monocytic cells is co
      ordinately regulated by ligand binding to both Mac-1 and uPAR and identify uPAR
      as a regulator of integrin function. Vitronectin-enhanced fibrin(ogen) turnover
      by Mac-1 may operate as a salvage pathway in the setting of urokinase and plasmin
      inhibitors to promote clearance of the provisional matrix and subsequent healing.

PMID- 8874220
TI  - Recombinant human eotaxin induces oxygen radical production, Ca(2+)-mobilization,
      actin reorganization, and CD11b upregulation in human eosinophils via a pertussis
      toxin-sensitive heterotrimeric guanine nucleotide-binding protein.
AB  - The novel human CC-chemokine Eotaxin is a potent and selective chemotaxin for
      eosinophils. Here, the biological activities and the activation profile of
      Eotaxin were further characterized and compared with those of other eosinophil
      chemotaxins such as complement fragment C5a (C5a), platelet-activating factor
      (PAF), and RANTES in human eosinophils. Eotaxin stimulated the production of
      reactive oxygen metabolites as shown by lucigenin-dependent chemiluminescence and
      superoxide dismutase-inhibitable cytochrome C reduction. Furthermore, Eotaxin
      induced upregulation of the integrin CD11b. In addition, fluorescence
      measurements with Fura-2-labeled eosinophils in the presence of EGTA indicated
      Ca(2+)-mobilization from intracellular stores by Eotaxin. Flow cytometric studies
      showed rapid and translent actin polymerization on stimulation with Eotaxin. At
      optimal concentrations, the changes induced by Eotaxin were comparable with those
      obtained by C5a, PAF, and RANTES. Call responses elicited by Eotaxin were
      inhibited by pertussis toxin, indicating coupling of its putative receptor to
      heterotrimeric guanine nucleotide-binding proteins. These results indicate that
      Eotaxin is a strong activator of eosinophils with biological activity comparable
      with those of the eosinophil chemotaxins C5a, PAF, and RANTES. These findings
      point to a role of Eotaxin in the pathogenesis of eosinophilic inflammation as a
      chemotaxin as well as an activator of proinflammatory effector functions.

PMID- 8874221
TI  - Ferritin uptake by human erythroid precursors is a regulated iron uptake pathway.
AB  - Iron delivery to mammalian cells is traditionally ascribed to diferric
      transferrin (Tf). We recently reported that human erythroid precursor cells
      possess specific membranes receptors that bind and internalize acid isoferritin.
      Here we show that ferritin uptake by these cells is highly regulated and that the
      internalized ferritin-iron is used for home synthesis and thus, this process
      could constitute a physiological pathway for iron assimilation. Ferritin was
      internalized by a specific, saturable process, distinct from the uptake of iron
      associated with albumin. Ferritin uptake downregulated transferrin-receptor
      expression, indicating that internalized ferritin-iron was recognized as an
      integral part of the cellular iron content. Ferritin receptor expression was
      coordinated to cell development and was tightly regulated by cellular iron
      status. Receptor abundance was increased by iron-depletion and decreased by iron
      loading, while the affinity of the ferritin receptor for acid isoferritin
      remained nearly constant (kd = 4.1 +/- 0.5 x 10(-6) mol/L). Under all
      experimental conditions, ferritin- and transferrin-receptor expression was
      closely coordinated, suggesting that these pathways possess a common regulatory
      element. It is concluded that ferritin uptake by erythroid cells constitutes an
      iron uptake pathway in addition to the classical transferrin uptake pathway.

PMID- 8874222
TI  - Two novel mutations in the reduced nicotinamide adenine dinucleotide (NADH)
      cytochrome b5 reductase gene of a patient with generalized type, hereditary
      methemoglobinemia.
AB  - Hereditary methemoglobinemia due to reduced nicotinamide adenine dinucleotide
      (NADH) cytochrome b5 reductase (b5R) deficiency is classified into two types, an
      erythrocyte (type I) and a generalized (type II). We investigated the b5R gene of
      a patient with type II from a white United Kingdom (UK) family and found that the
      patient was a compound heterozygote for two novel mutations. The first mutation
      was a C-to-A transversion changing codon 42 (TAC: Tyr) to a stop codon in the one
      allele. From this mutant allele, the product without the catalytic portion of the
      enzyme is generated. The second one was a missense mutation at codon 95 (CCC-
      >CAC) in the other allele with the result that Pro changed to His within the
      flavin adenine dinucleotide (FAD)-binding domain of the enzyme. To characterize
      effects of this missense mutation on the enzyme function, we compared glutathione
      S-transferase (GST)-fused b5R with the GST-fused mutant enzyme with the codon 95
      missense mutation (P95H) expressed in Escherichia coll. The mutant enzyme showed
      less catalytic activity, less thermostability, and a greater susceptibility to
      trypsin than did the normal counterpart. The absorption spectrum of the mutant
      enzyme in the visual region differed from that of the wild-type. These results
      suggest that this amino acid substitution influences both secondary structure and
      catalytic activity of the enzyme. The compound heterozygosity for the nonsense
      and the missense mutations apparently caused hereditary methemoglobinemia type II
      in this patient.

PMID- 8874223
TI  - Alloimmunization to platelets in heavily transfused patients with sickle cell
      disease.
AB  - Bone marrow transplantation (BMT) is now an option for some patients with sickle
      cell disease (SCD). Many SCD patients are multiply transfused with red blood
      cells (RBCs), and may be immunized to alloantigens other than erythrocyte
      antigens. Because platelet refractoriness is a significant complication during
      BMT, we wished to determine the prevalence of alloimmunization to platelets in
      transfused SCD patients. Sera collected from 47 transfused and 14 untransfused
      SCD patients were screened for HLA and platelet-specific antibodies. Transfusion
      and RBC antibody histories were reviewed. A subset of the patients were
      rescreened 1 year later. Eighty-five percent of patients with at least 50 RBC
      transfusions (22 of 26), 48% of patients with less than 50 transfusions (10 of
      21), and none of 14 untransfused patients demonstrated platelet alloimmunization
      (P < .05). Platelet alloimmunization was more prevalent than RBC alloimmunization
      (20% to 30%). Half of the platelet reactivity was chloroquine-elutable. Eighteen
      of 22 patients (82%) on chronic RBC transfusion remained platelet-alloimmunized
      11 to 22 months after initial testing. In summary, 85% of heavily transfused SCD
      patients are alloimmunized to HLA and/or platelet-specific antigens. These
      patients may be refractory to platelet transfusion, a condition that would
      increase their risk during BMT. Leukodepletion in the transfusion support of SCD
      patients should be considered to prevent platelet alloimmunization.

PMID- 8874224
TI  - CD34+ cell dose predicts survival, posttransplant morbidity, and rate of
      hematologic recovery after allogeneic marrow transplants for hematologic
      malignancies.
AB  - After autologous or allogeneic transplants of peripheral blood stem cells (PBSC),
      an adequate dose of CD34+ cells is necessary to ensure early and sustained
      hematopoietic engraftment and favorable clinical outcome. There are no comparable
      data on the relationship between CD34+ cell dose and recovery after allogeneic
      bone marrow transplants (BMT). Twenty-eight patients with hematologic
      malignancies received a BMT from an HLA-identical sibling, using T-cell depletion
      and cyclosporin for graft-versus-host disease prophylaxis and delayed donor
      lymphocyte transfusions in an attempt to prevent leukemia relapse. The treatment
      related mortality (TRM), primarily due to infections and cytopenias, was
      significantly higher for 13 patients receiving less than 1 x 10(6) CD34+ cells/kg
      (64.9% +/- 12.8% v 6.9% +/- 6.4%, P = .003). Survival at a median follow-up of 1
      year was also lower in the group receiving less than 1 x 10(6) CD34+ cells/kg
      (30.8% +/- 12.8 v 74.3% +/- 13.7%, P = .005). The CD34+ cell dose was the only
      variable significantly associated with TRM. The dose of CD34+ cells also
      correlated with speed of hematopoistic recovery. Patients receiving more than 2 x
      10(6) CD34+ cells/kg showed significantly earlier recovery of monocytes and a
      trend for earlier recovery of lymphocytes. They achieved platelet and red blood
      cell transfusion independence earlier, required less granulocyte colony
      stimulating factor support during ganciclovir treatment, and spent fewer days in
      the hospital after transplantation. These results suggest that, for allogeneic T
      cell-depleted BMT, the higher CD34+ cell doses may improve outcome in engrafting
      patients.

PMID- 8874226
TI  - Genotyping for human platelet antigen-1 directly from dried blood spots on cards.

PMID- 8874225
TI  - Presence of t(2;5) in primary CD30+ cutaneous lymphoproliferative disorders.

PMID- 8874227
TI  - Lack of beta-oxidation defects in human immunodeficiency virus-positive subjects
      with and without chronic zidovudine exposure.

PMID- 8874228
TI  - Pure red cell aplasia: its clinical association and treatment.

PMID- 8874229
TI  - Response: pure red blood cell aplasia: association with large granular lymphocyte
      leukemia and the prognostic value of cytogenetic abnormalities.

PMID- 8874230
TI  - Lack of relationship between soluble erythropoietin receptor levels and erythroid
      parameters in anemic patients.

PMID- 8874232
TI  - beta-Thalassemia mutation at -90C-->T impairs the interaction of the proximal
      CACCC box with both erythroid and nonerythroid factors.

PMID- 8874234
TI  - The American College of Radiology appropriateness criteria. Will they be useful
      for us?

PMID- 8874233
TI  - Systemic corticosteroids in COPD. An unresolved clinical dilemma.

PMID- 8874235
TI  - Dornase alfa therapy in cystic fibrosis: who should get it?

PMID- 8874236
TI  - Endogenous nitric oxide in exhaled human breath. A new means of monitoring airway
      disease activity or another no-no?

PMID- 8874238
TI  - Enhancing mucociliary clearance.

PMID- 8874237
TI  - ICU stay after single lung transplantation.

PMID- 8874239
TI  - Lung volume reduction surgery in ventilator-dependent COPD patients.
AB  - BACKGROUND: Lung volume reduction surgery has been advocated recently as
      adjunctive surgical therapy to improve lung and chest wall mechanics in selected
      patients with diffuse emphysema. Although clear-cut guidelines to select
      candidates have not been fully established, patients decompensated with
      significant pulmonary artery hypertension and hypercapnic respiratory failure are
      currently not considered suitable subjects. Accordingly, ventilator-dependent
      COPD patients are not considered candidates for this procedure. However, because
      ventilator-dependent COPD patients have an exceptionally poor prognosis, we
      elected to offer them this promising, but unproved surgical intervention. Herein,
      we describe the outcome of these three patients. PATIENTS: The 3 patients had
      recurrent exacerbations of COPD precipitating respiratory failure, and following
      aggressive medical therapy remained mechanically ventilated for 11 to 16 weeks (1
      patient had a brief period of successful weaning before returning to mechanical
      ventilation). Prior to surgery, the patients had severe hypercapnia and cor
      pulmonale. Compared with preoperative values, surgery resulted in improvements in
      PaO2/FIO2, 304 +/- 80 (SD) vs 229 +/- 48 mm Hg, reductions in PaCO2, 44 +/- 3 vs
      60 +/- 9 mm Hg, increases in FVC, 1.63 + 0.52 vs 1.09 +/- 0.05 L, and maximum
      inspiratory pressure, 57 +/- 22 vs 29 +/- 12 cm H2O. Postoperative complications
      included persistent air leaks and one tension pneumothorax. Patients weaned from
      mechanical ventilation after 10 to 21 days all were discharged home and they
      continue to demonstrate improved gas exchange and functional status. CONCLUSIONS:
      Lung volume reduction surgery in select, ventilator-dependent COPD patients can
      result in improved gas exchange and respiratory mechanics that enable successful
      weaning and overall improved functional status.

PMID- 8874240
TI  - Combined operations for lung volume reduction surgery and lung cancer.
AB  - Fifty-three lung masses were found in 51 (16%) of 325 patients who underwent lung
      volume reduction surgery. This included 11 non-small cell lung cancers and 42
      benign lung masses. Eleven patients (mean age, 69.4 years) underwent a combined
      lung volume reduction surgery and resection of clinical stage I lung cancers
      (lymph node dissection with either lobectomy [3] or wedge resection [8]). There
      were no deaths or major complications. The average length of stay was 8.7 days.
      The mean FEV1 was 654 mL (21.7% predicted) preoperatively and 1,079 mL (49%
      predicted) postoperatively. Patients who are screened for lung volume reduction
      surgery should be carefully evaluated for possible lung masses. Lung volume
      reduction surgery allows lung cancer surgery in patients who otherwise would be
      considered to have physiologically inoperable disease.

PMID- 8874241
TI  - Effects of 12-week administration of dornase alfa in patients with advanced
      cystic fibrosis lung disease. Pulmozyme Study Group.
AB  - STUDY OBJECTIVE: The 12-week efficacy and safety of aerosolized recombinant human
      DNase (dornase alfa) were evaluated in previously untreated patients with cystic
      fibrosis (CF) with advanced lung disease. DESIGN: In this multicenter, double
      blind, placebo-controlled study, CF patients with advanced lung disease were
      randomized to receive either dornase alfa or placebo once a day for 12 weeks.
      PATIENTS: A total of 320 patients in clinically stable condition with documented
      CF and an FVC less than 40% of predicted were recruited from 65 CF Foundation
      care centers in the United States. The dornase alfa and placebo groups were
      comparable with respect to age (range, 7 to 57 years), height, and weight. Male
      subjects outnumbered female subjects (55% vs 45%) and few subjects were younger
      than 17 years of age (15%). The percentages of predicted FEV1 and FVC were
      significantly lower in the dornase alfa group at baseline (p < or = 0.05).
      INTERVENTIONS: Patients were randomly assigned to receive either 2.5 mg dornase
      alfa once daily (n = 158) or placebo once daily (n = 162). All patients continued
      to receive standard medications and treatments administered for CF. MEASUREMENTS
      AND RESULTS: Dornase alfa improved the mean percent change in FEV1 from baseline
      by 9.4% compared with 2.1% for placebo (p < 0.001). The actively treated group
      showed a 12.4% improvement in FVC compared with 7.3% for placebo (p < 0.01).
      There were no differences between the treatment groups in dyspnea score number of
      days receiving i.v. antibiotics, or length of hospital stay; the overall
      incidence of adverse events was comparable between treatment groups. Fifteen
      patients died: 9 in the dornase alfa group and 6 in the placebo group; no
      differentiating clinical characteristics were demonstrated. CONCLUSIONS:
      Pulmonary function as measured by FEV1 and FVC improved significantly in the
      dornase alfa-treated patients. Dornase alfa was found to be safe and well
      tolerated over the 12-week study period.

PMID- 8874242
TI  - Physiologic factors that determine the health-related quality of life in patients
      with COPD.
AB  - STUDY OBJECTIVE: To determine the physiologic factors that influence the health
      related quality of life (HRQL) in patients with stable COPD and to identify the
      factors that most influence HRQL. METHODS: The Nottingham Health Profile (NHP)
      was used as a general HRQL measure and the Chronic Respiratory Disease
      Questionnaire (CRQ) was used as a disease-specific HRQL measure to investigate
      132 patients with stable COPD, and measurements of HRQL were compared with
      physiologic measures. RESULTS: Vital capacity, FEV1, the ratio of the FEV1 to the
      FVC, diffusion capacity for carbon monoxide, diffusion capacity corrected for
      alveolar volume, lifetime cigarette consumption expressed as pack-years, and age
      were weakly correlated with several dimensions of both the NHP and the CRQ.
      Factor analysis reduced these variables to three factors. Two factors mainly
      referring to airflow limitation and diffusing capacity were weakly correlated
      with several dimensions of both the NHP and the CRQ. Logistic regression analysis
      identified 4 independent predictors of HRQL: airflow limitation (odds ratio [OR]
      = 0.59 to 0.69), diffusing capacity (OR = 0.75 to 0.82), pack-years (OR = 1.20 to
      1.23), and age (OR = 2.13). The CRQ was more sensitive to impairment of HRQL than
      the NHP. CONCLUSIONS: The HRQL of patients with stable COPD is partly determined
      by airflow limitation, diffusing capacity, pack-years, and age. However, these
      factors could not predict the whole spectrum of HRQL, and the contribution of
      these factors to HRQL was limited. Therefore, HRQL should be measured directly in
      addition to physiologic measures.

PMID- 8874244
TI  - Airway hyperresponsiveness to methacholine in subjects with spinal cord injury.
AB  - Previously, we found that never-smokers with quadriplegia were hyperresponsive to
      aerosolized methacholine. To further explore the phenomenon, we compared
      responsiveness to methacholine in never-smokers with that of smokers and ex
      smokers. We also evaluated responsiveness in subjects with high paraplegia
      (lesions at T-1 to T-6) or low paraplegia (lesions at T-7 and below). We found
      that smokers and ex-smokers with quadriplegia were hyperresponsive to
      methacholine (provocative concentration causing a 20% fall in FEV1 = 1.9 mg/mL),
      and that the response was comparable to that found in never-smokers, revealing
      that hyperresponsiveness among never-smokers cannot be attributed to preinjury
      airway hyperreactivity that precluded cigarette use. In contrast, subjects with
      low paraplegia were not hyperresponsive to methacholine. Among subjects with high
      paraplegia, the three subjects demonstrating airway hyperresponsiveness had
      significantly lower FEV1 (percent predicted). The findings support the hypothesis
      that airway hyperresponsiveness in subjects with quadriplegia represents loss of
      sympathetic innervation of the lung, thereby leaving intact unopposed
      bronchoconstrictor cholinergic activity. However, reduced lung volumes in these
      subjects also suggest the possibility that airway hyperresponsiveness is due to
      loss of ability to stretch airway smooth muscle by deep breathing.

PMID- 8874243
TI  - Acute effects of inhaled and i.v. cocaine on airway dynamics.
AB  - BACKGROUND: Wheezing has been reported by 32% of habitual smokers of crack
      cocaine, and several cases of crack-related acute exacerbations of asthma have
      been reported. STUDY OBJECTIVE: To compare the acute effects of physiologically
      active doses of smoked cocaine base and, i.v. cocaine hydrochloride (HCl), a
      subphysiologic dose of cocaine base (smoked "placebo"), and i.v. saline solution
      placebo on bronchomotor tone, subjective level of intoxication, and
      cardiovascular responses in healthy habitual crack users. DESIGN: A single-blind
      crossover study in which the order of route of administration (inhaled vs i.v.)
      was random but placebo always preceded the active drug. SUBJECTS: Fourteen
      healthy, nonasthmatic current crack-smoking subjects, 34 to 48 years of age, with
      a history of previous i.v. cocaine use (1 to 12 times per lifetime). METHODS:
      Heart rate, BP, self-rated level of intoxication (scale of 0 to 10), and
      measurements of airway resistance (Raw) and specific airway conductance (SGaw)
      were recorded during separate sessions before and 3 to 5, 10, 15, and 30 min
      after administration of smoked cocaine base (38.5 +/- 2.3 [SEM] mg), smoked
      placebo (2.3 +/- 0.9 mg cocaine base), i.v. cocaine HCl (30.0 +/- 2.0 mg), and
      i.v placebo (saline solution). RESULTS: Both smoked active cocaine and i.v.
      cocaine HCl caused comparable, significant (p < 0.05) peak levels of acute
      intoxication (6.7 +/- 0.7 and 7.3 +/- 0.8, respectively) and increases in heart
      rate from baseline (29.6 +/- 2.9% and 21.4 +/- 3.7%, respectively, at 5 min).
      However, only smoked active cocaine caused significant decreases from baseline in
      SGaw (25.4 +/- 6.3% at 5 min), in contrast to nonsignificant changes after i.v.
      cocaine HCl (5.6 +/- 7.0% increase) and smoked placebo (10.2 +/- 6.0% decrease).
      CONCLUSIONS: Smoked cocaine base, but not systemically administered cocaine HCl,
      causes acute bronchoconstriction that is probably mediated by local airway
      irritation and could account for reports of crack-induced wheezing and asthma
      attacks in nonasthmatic and asthmatic individuals, respectively.

PMID- 8874245
TI  - Adaptation of lung antioxidants to cigarette smoking in humans.
AB  - We investigated the effect of free radical scavengers, micronutrient
      antioxidants, on antioxidant enzyme activities in cigarette smokers. We measured
      the intracellular superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GPx) activities and vitamin E and beta-carotene levels in the
      bronchoalveolar cells of 14 smokers before and after 6 weeks of supplementation
      with vitamins E and C and beta-carotene. Eight nonsmokers served as control
      subjects. CAT and GPx activities were higher in BAL cells from smokers compared
      with nonsmokers (20.5 +/- 2.3 vs 9.6 +/- 1.3 U/10(6) cells; p = 0.027; 0.90 +/-
      0.10 vs 0.46 +/- 0.12 U/10(6) cells; p = 0.049, respectively), while there was no
      difference in SOD activity between the two groups. Likewise, vitamin E and beta
      carotene concentrations were markedly higher in smokers' lung lavage cells (403.3
      +/- 81.0 in smokers vs 16.6 +/- 5.3 ng/10(6) cells in nonsmokers, and 1.23 +/-
      0.21 in smokers vs 0.15 +/- 0.04 ng/10(6) cells in nonsmokers, respectively). The
      serum levels of vitamin E and C and beta-carotene increased by 2.0-, 1.6-, and
      8.9-fold in smokers after supplementation, which were similar to nonsmokers.
      Similarly, BAL cell vitamin E increased from 403.3 +/- 81.0 to 477.4 +/- 97.7
      ng/10(6) cells and beta-carotene increased from 1.23 +/- 0.21 to 4.32 +/- 0.45
      ng/10(6) cells (p < 0.05). Despite increased concentrations of vitamins in serum
      as well as beta-carotene levels in BAL cells, there was no significant down
      regulation in SOD, CAT, or GPx activities in the lung lavage cells. These data
      suggest that augmentation of micronutrient antioxidants in smokers and nonsmokers
      does not appear to have an effect on antioxidant enzyme activities, suggesting a
      differential regulation of these defenses.

PMID- 8874246
TI  - Cigarette smoking habits among schoolchildren.
AB  - STUDY OBJECTIVE: Cigarette smoking is a major preventable cause of morbidity and
      mortality worldwide. Most adult smokers start smoking regularly some time before
      18 years of age. The aim of this study was to determine the age at which children
      begin cigarette smoking, to study the environmental factors that influence
      children to smoke, and to understand the reasons why children smoke. The results
      of this study may help lead to the development of more effective smoking
      prevention programs. METHODS: We carried out a cross-sectional survey of all
      students in grades 6 to 11 (ages: 11 to 17 years) in two high schools in the
      Jerusalem area, using an anonymous self-completion questionnaire. The students
      were asked questions regarding the age at which they began smoking, initiation,
      their smoking habits, their reasons for smoking, and their views on children who
      smoke. In addition, they were asked about the smoking status of their parents,
      siblings, and friends. Finally they were asked about the health hazards of
      smoking. RESULTS: Of the 847 students who answered the questionnaire, 35% stated
      that they had smoked at least once and 14% stated that they were currently
      smoking. The percentage of students who were currently smoking increased
      gradually with age to 36%. There was a sharp increase in experimental smoking
      after seventh grade (ages 12 to 13 years). Having a friend who smoked
      substantially increased the likelihood of smoking, whereas parental smoking or
      having a sibling who smoked did not increase the likelihood of smoking. The most
      common reason for starting to smoke was "to try something new" (55%). There was a
      significant difference between the views of students with different smoking
      statuses regarding children who smoke: nonsmoking children associated more
      negative characteristics to smoking. All of the children studied were well aware
      of the health hazards of cigarette smoking. CONCLUSIONS: Smoking is highly
      prevalent among schoolchildren in Jerusalem. The increase in the rate of smoking
      at the age of 12 years indicates that smoking prevention programs need to be
      started at an earlier age. Peer pressure is a very strong stimulus for smoking in
      children. Since children are aware of the health hazards of smoking, prevention
      policy should be aimed more at associating smoking with negative images and
      addressing peer pressure.

PMID- 8874247
TI  - Role of endogenous nitric oxide in airflow obstruction in smokers.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between
      endogenous nitric oxide (NO) level and airflow obstruction in smokers using
      single-breath measurement of exhaled NO with the sequential breath-holding
      method. SETTING: A university hospital. PATIENTS: Nine nonsmoking and ten smoking
      healthy volunteers. MEASUREMENTS: NO in exhaled air was measured using a
      chemiluminescence analyzer. Pulmonary function tests were performed using an
      autospirometer. RESULTS: The level of exhaled NO was higher in nonsmokers than in
      smokers, and the difference became larger as the breath-holding time increased.
      To evaluate the correlation between endogenous NO level and the degree of airflow
      obstruction in smokers, we used a new parameter, the NO concentration difference
      (delta NO). Our findings indicate that reduced level of NO in exhaled air is an
      indicator of decreased NO synthesis within the respiratory system and is
      associated with the development of airflow obstruction in smokers (r = 0.678; p <
      0.01). CONCLUSIONS: delta NO is a good indicator of the synthesis of endogenous
      NO within the respiratory system, and it appears likely that the reduced
      synthesis of NO may be a contributing factor to airflow obstruction in smokers.

PMID- 8874248
TI  - Origins of breath nitric oxide in humans.
AB  - STUDY OBJECTIVES: Nitric oxide (NO) exists in the human breath, but little is
      known about its site of origin or enzyme source. The aims of this study were to
      locate the main site of NO release into human breath and to decide whether the
      inducible isoform of NO synthase (iNOS) and nasal bacteria contribute to breath
      NO. DESIGN: Using a chemiluminescence assay, NO levels were measured in air
      exhaled from the nose, mouth, trachea, and distal airway. The susceptibility of
      breath NO to treatment with a topical corticosteroid (to inhibit iNOS; intranasal
      beclomethasone dipropionate for 2 weeks) and with antibiotics (systemic
      amoxicillin plus clavulanic acid and intranasal bacitracin zinc, 5 to 10 days)
      was also tested. PARTICIPANTS: Twenty-one healthy subjects, 9 intubated patients,
      and 7 patients undergoing bronchoscopy. All subjects were nonsmokers free of
      pneumonia, rhinitis, and bronchitis. MEASUREMENTS AND RESULTS: Breath NO levels,
      collected in the gas sampling bags, were greater (p < 0.05) in the nose (25 +/- 2
      parts per billion [ppb]) than in the mouth (6 +/- 1 ppb), trachea (3 +/- 1 ppb),
      or distal airway (1 +/- 2 ppb). Similar results were obtained when NO was sampled
      directly by cannula from nose or mouth during resting breathing. Nasal breath NO
      signal increased sharply during 30 s of breath-holding. Beclomethasone, but not
      antibiotics, decreased nasal NO levels without changing oral breath NO.
      CONCLUSIONS: Most NO in normal human breath derives locally from the nose where
      it can reach high levels during breath-holding. NO is synthesized, at least in
      part, by a steroid-inhibitable, nonbacterial, NO synthase, presumably iNOS.

PMID- 8874249
TI  - Urinary leukotriene E4 levels in high-altitude pulmonary edema. A possible role
      for inflammation.
AB  - STUDY OBJECTIVES: Inflammation may contribute to the pathogenesis of high
      altitude pulmonary edema (HAPE). This study was designed to determine whether a
      marker of inflammation, urinary leukotriene E4 (LTE4), is elevated in patients
      with HAPE. DESIGN: We conducted a case-control study to collect clinical data and
      urine samples from HAPE patients and healthy control subjects at moderate
      altitude (> or = 2727 m), and follow-up urine samples from HAPE patients
      following their return to low altitude (< or = 1,600 m). SETTING: Five medical
      clinics in Summit County, Colorado. PATIENTS: Questionnaire data were evaluated
      in 71 HAPE patients and 36 control subjects. Urinary LTE4 levels were determined
      from a random subset of 38 HAPE patients and 10 control subjects presenting at
      moderate altitude, and on 5 HAPE patients who had returned to low altitude.
      MEASUREMENTS AND RESULTS: Using an enzyme immunoassay technique, urinary LTE4
      levels were found to be significantly higher in HAPE patients (123 [16 to 468]
      pg/mg creatinine, geometric mean [range]) than in control subjects (69 [38 to
      135]), p = 0.02. Following return to low altitude, urinary LTE4 levels fell
      significantly from 122 (41.8 to 309) to 53.6 (27.6 to 104) pg/mg creatinine (p =
      0.05). Urinary LTE4 levels were not related to age, sex, time at altitude,
      physical condition or habitual exercise, recent use of alcohol or nonsteroidal
      anti-inflammatory drugs (NSAIDs), or oxygen saturation. Clinical factors
      associated with HAPE included male sex, regular exercise, and recent use of
      NSAIDs. CONCLUSIONS: We conclude that urinary LTE4 levels are elevated in
      patients with HAPE, supporting the view that HAPE involves inflammatory
      mechanisms.

PMID- 8874250
TI  - Urinary leukotriene E4 levels increase upon exposure to hypobaric hypoxia.
AB  - STUDY OBJECTIVE: To determine whether urinary leukotriene E4 (uLTE4) levels
      increase upon exposure to high altitude, and also to ascertain the relationship
      between uLTE4 levels and symptoms of acute mountain sickness (AMS). DESIGN:
      Prospective, unblinded, single-factor (altitude) experimental study. SETTINGS: US
      Army research laboratory facilities at sea level ([SL] 50 m), 1,830 m, and 4,300
      m. PARTICIPANTS: Eight healthy male subjects ranging in age from 19 to 24 years.
      MEASUREMENTS: uLTE4 levels and symptoms of AMS were measured at just above SL (50
      m), 3 1/2 days after being transported from SL to moderate altitude (MA) (1,830
      m), and 1 1/2 days after ascent from 1,830 to 4,300 m (high altitude [HA]).
      Symptoms of AMS were assessed using standard indexes derived from the
      Environmental Symptoms Questionnaire weighted toward cerebral (AMS-C) and
      respiratory (AMS-R) manifestations. Oxygen saturation was measured noninvasively
      by pulse oximetry at SL and HA. RESULTS: The mean (+/-SEM) uLTE4 levels (pg/mg
      creatinine) were 67.9 (+/-13.2) at SL; 82.3 (+/-5.5) at MA; and 134.8 (+/-19.4)
      at HA (p < 0.05 comparing HA with SL and MA). CONCLUSIONS: We conclude that uLTE4
      levels increase shortly after exposure to HA even after staging for 4 days at MA.
      Although this study does not clearly demonstrate a relationship between uLTE4
      levels and symptoms of AMS, it supports the hypothesis that leukotrienes may be
      involved in the pathophysiologic state of AMS.

PMID- 8874251
TI  - Patients with acute hyperventilation presenting to an inner-city emergency
      department.
AB  - We studied 23 consecutive patients with acute hyperventilation presenting to an
      inner-city emergency department, diagnosed on clinical grounds by the attending
      physician and confirmed by arterial blood gas values in 5 patients. An organic
      basis for the presenting complaints was excluded and chest radiograph, serum
      biochemistry, blood cell count, and thyroid function test results were normal.
      The male to female ratio was 12:11. Presenting complaints were dyspnea (61%),
      paresthesia (35%), chest pain or tightness (43%), muscle spasm (9%), dizziness
      (13%), palpitations (13%), and panic (30%). Similar previous episodes were
      reported in 74%. Misattribution of the presenting complaints to a cardiac or
      other life-threatening disorder was reported in 20 patients (87%) and was the
      main reason for their presentation to the hospital. Although no patients
      presented with clinical features of asthma, 7 (30%) were known asthmatics
      receiving treatment and another 10 (44%) had a history and investigation results
      suggestive of asthma. Only 2 had a history of anxiety or depression, but 17 (78%)
      patients exceeded the threshold for anxiety or panic on Clinical Interview
      Schedule (CIS-R) interview (score > or = 12). Marihuana or alcohol abuse were
      involved in 17% with a history of past abuse in 26%. When assessed 2 months after
      the attack, 13 (57%) had resting or stressor-induced hyperventilation with a
      significant (p < 0.05) association with asthma but not with a positive CIS-R
      score. These results illustrate the multifactorial basis of acute
      hyperventilation, the importance of misattribution, and the danger of using the
      term "hyperventilation syndrome" in the emergency department.

PMID- 8874252
TI  - Arterial blood gas changes during breath-holding from functional residual
      capacity.
AB  - Breath-holding serves as a model for studying gas exchange during clinical
      situations in which cessation of ventilation occurs. We chose to examine the
      arterial blood gas changes that occurred during breath-holding, when breath
      holding was initiated from functional residual capacity (FRC) while breathing
      room air. Eight normal subjects who had a radial artery catheter placed for
      another study were taught to breath-hold on command from FRC. FRC was determined
      using respiratory inductance plethysmography. Arterial blood gas specimens were
      obtained at 5-s intervals until the termination of breath-holding. The average
      breath-holding time (+/-SD) was 35 (+/-10 s). The PaO2, PaCO2, and pH values were
      plotted against time and individually fit to logistic equations for each subject.
      The arterial PaO2 fell by a mean of 50 mm Hg during the first 35 s of breath
      holding under these conditions, while the arterial PCO2 rose by a mean of 10.2 mm
      Hg during the first 35 s and the pH fell by a mean of 0.07 in the first 35 s. The
      rapid decline in PaO2 is greater than that previously reported using different
      methods and should be considered in clinical situations in which there is an
      interruption of oxygenation and ventilation at FRC while breathing room air. The
      changes in PaCO2 and pH are similar to those previously reported in paralyzed
      apneic patients.

PMID- 8874253
TI  - A prospective randomized study of inpatient iv. antibiotics for community
      acquired pneumonia. The optimal duration of therapy.
AB  - STUDY OBJECTIVE: To compare therapeutic outcome and perform a cost-benefit
      analysis of inpatients with community-acquired pneumonia (CAP) treated with a
      shortened course of i.v. antibiotic therapy. DESIGN: A prospective, randomized,
      parallel group study with a follow-up period of 28 days. SETTING: Bronx Veterans
      Affairs Medical Center (VAMC) and the Castle Point VAMC; university-affiliated
      VAMC general medical wards from September 1993 to March 1995. PATIENTS: Seventy
      two male veterans and 1 female veteran with 75 episodes of CAP defined by a new
      infiltrate on chest radiograph and either history or physical findings consistent
      with pneumonia. Study population was 42%(31) black, 33%(24) white, and 25%(18)
      Hispanic. INTERVENTIONS: Patients were randomized (1:1:1) to 1 of 3 treatment
      groups: group 1 received 2 days of i.v. and 8 days of oral therapy; group 2
      received 5 days of i.v. and 5 days of oral therapy; and group 3 received 10 days
      of i.v. therapy. Antibiotics consisted of cefuroxime, 750 mg every 8 h for the
      i.v. course, and cefuroxime axetil, 500 mg every 12 h for the oral therapy.
      MEASUREMENTS AND RESULTS: No differences were found in the clinical course, cure
      rates, or resolution of chest radiograph abnormalities among the three groups. A
      significant difference was found in the length of stay (LOS) among the three
      groups. The mean +/- SD LOS was 6 +/- 3 days in group 1, 8 +/- 2 days in group 2,
      and 11 +/- 1 days in group 3. The shortened LOS could potentially save $95.5
      million for the Department of Veterans Affairs and $2.9 billion for the US
      private sector. CONCLUSIONS: Adult patients hospitalized for CAP who are not
      severely ill can be successfully treated with an abbreviated (2-day) course of
      i.v. antibiotics and then switched to oral therapy. A longer course of i.v.
      therapy prolongs hospital stay and cost, without improving the therapeutic cure
      rate.

PMID- 8874254
TI  - Detection of Mycoplasma pneumoniae by polymerase chain reaction in lung aspirates
      from patients with community-acquired pneumonia.
AB  - STUDY OBJECTIVE: This study was designed to evaluate the usefulness of polymerase
      chain reaction (PCR) to detect Mycoplasma pneumoniae DNA in samples obtained by
      transthoracic needle aspiration (TNA). DESIGN: Prospective study of cases.
      SETTING: A university hospital in Lleida, Spain. PATIENTS: A total of 101
      unselected patients, admitted between January 1993 and March 1994 in the
      emergency department, with a clinical and radiologic picture of community
      acquired pneumonia, and without contraindications for TNA application.
      INTERVENTIONS: Patients were studied with conventional diagnostic techniques for
      community-acquired pneumonia. In addition, a sample obtained by TNA was processed
      by the following methods: culture in standard media, culture in selective media
      for Legionella, detection of capsular antigens for Streptococcus pneumoniae and
      Haemophilus influenzae, and detection of M pneumoniae specific genome by PCR.
      RESULTS: Serologic data were not available in eight patients and were excluded
      from this analysis. M pneumoniae PCR amplification was possible in eight cases,
      well correlated with serologic responses indicating current infection. Samples
      from ten additional patients, negative by PCR, were found to be demonstrative of
      recent M pneumoniae infection by serologic study. Finally, in all the remaining
      75 cases, including the 59 patients for whom a different microbial diagnosis was
      established, M pneumoniae PCR test gave negative results. CONCLUSION: This study
      indicates that PCR, applied to samples obtained by TNA, appears to be a
      moderately sensitive and highly specific method for rapid detection of M
      pneumoniae lung infection.

PMID- 8874255
TI  - Utility of CT in the evaluation of pulmonary tuberculosis in patients without
      AIDS.
AB  - OBJECTIVE: To assess the utility of CT in the evaluation of pulmonary
      tuberculosis in patients without AIDS. PATIENTS AND METHODS: This-section CT
      scans for suspicion of pulmonary tuberculosis were obtained from 226 patients. A
      total of 38 patients were excluded; the reasons were unavailability of final
      results (n = 18), patient unavailability for follow-up (n = 13), and coexistence
      of tuberculosis and aspergilloma (n = 7). The results from 188 patients were used
      for this study. After assessing the patterns of parenchymal lesion, involved
      segments, and presence of cavity, bronchiectasis, and bronchogenic spread of the
      lesion with CT, tentative diagnosis and disease activity were recorded. RESULTS:
      With CT, 133 of 146 patients (91%) with tuberculosis were correctly diagnosed as
      having pulmonary tuberculosis whereas 32 of 42 patients (76%) without
      tuberculosis were correctly excluded. CT diagnosis of lung cancer (n = 8),
      bacterial pneumonia (n = 2), pulmonary metastasis (n = 1), chronic
      hypersensitivity pneumonia (n = 1), and diffuse panbronchiolitis (n = 1) turned
      out to be tuberculosis. Conversely CT diagnoses of tuberculosis appeared
      pathologically as lung cancer (n = 5), bacterial pneumonia (n = 4), and pulmonary
      paragonimiasis (n = 1). Active (71/89, 80%) and inactive state (51/57, 89%) of
      disease respectively could be correctly differentiated by CT. CONCLUSION: CT can
      be helpful in the diagnosis of pulmonary tuberculosis in most cases. On the basis
      of CT findings, distinction of active from inactive disease can be made in most
      cases.

PMID- 8874256
TI  - Effect of physical training on exercise capacity and gas exchange in patients
      with chronic heart failure.
AB  - Decreased exercise capacity is the main factor restricting the daily life of
      patients with chronic congestive heart failure (CHF). We performed a controlled,
      randomized study to evaluate the effect of dynamic exercise training of moderate
      intensity on exercise capacity and gas exchange in patients with CHF. Twenty
      seven patients with stable CHF, New York Heart Association (NYHA) functional
      class II and III, were randomized to training (n = 12) and control (n = 15)
      groups. During a 3-month period, the training group underwent a supervised
      physical training program using a bicycle ergometer for 30 min 3 times a week at
      a load corresponding to 50 to 60% of their peak oxygen consumption. Thereafter,
      they were advised to continue training at home for the next 3 months. The control
      group did not change their previous physical activity. A graded maximal exercise
      test with respiratory gas analysis and an endurance test with constant submaximal
      workload were performed at baseline and after 3 and 6 months. The exercise
      endurance increased from 14.7 +/- 2.0 to 27.8 +/- 2.7 min (p < 0.01) and the peak
      oxygen consumption tended to improve from 19.3 +/- 1.6 to 21.7 +/- 2.3 mL/kg/min
      (p = 0.09) during the supervised training period. At submaximal workloads, minute
      ventilation was reduced by 16% per se (p < 0.01) and by 7% in proportion to
      carbon dioxide production (p < 0.05). Oxygen consumption at the anaerobic
      threshold increased from 10.5 +/- 0.8 to 12.7 +/- 1.0 mL/kg/min (p < 0.05). The
      positive training effects were associated with an improvement in the NYHA
      functional class. The effects of supervised training were preserved during the
      home-based training period. The results indicate that physical training of
      moderate intensity significantly improves the exercise capacity and reduces the
      exaggerated ventilatory response to exercise, particularly at submaximal working
      levels in patients with CHF. This is associated with alleviation of symptoms.

PMID- 8874257
TI  - The clinical relevance of circulating tumor necrosis factor-alpha in acute
      decompensated chronic heart failure without cachexia.
AB  - STUDY OBJECTIVE: To evaluate the clinical relevance of circulating tumor necrosis
      factor-alpha (TNF alpha) in subjects with advanced acutely decompensated
      congestive heart failure (CHF) and to determine the modulatory effect of clinical
      interventions on short-term elaboration of this cytokine. DESIGN: Prospective,
      case-controlled study. SETTING: Inpatient and outpatient (hospital and clinic),
      at regional academic medical center. PATIENT INTERVENTIONS: Plasma concentrations
      of TNF alpha were determined in 25 healthy, normal control subjects and in 29
      noncachectic patients with advanced CHF (mean ejection fraction = 16 +/- 6%) who
      required hospitalization for i.v. diuretic and/or inotropic therapy despite
      optimization of oral medical regimens. CHF patients were divided into two groups:
      diuretic responsive (group A; n = 6) and diuretic resistant requiring inotropic
      support (group B; n = 23). Group B was randomly allocated to receive either i.v.
      dobutamine (n = 13) or milrinone (n = 10) for 72 h. TNF alpha levels in CHF
      patients were measured serially at baseline, at 6 h, at 48 h, at 72 h, and at 1
      week follow-up after hospital discharge. RESULTS: Plasma TNF alpha levels at
      baseline in CHF patients were 4.0 +/- 1.1 pg/mL (range, 0.5 to 6.5 pg/ mL) and
      2.5 +/- 0.6 pg/mL (range, 0.5 to 6.8 pg/mL) in groups A and B, respectively,
      which were significantly different (p < 0.002) from normal subjects (0.89 +/-
      0.40 pg/mL; range, 0.5 to 9.7 pg/mL). Despite clinically successful therapy with
      i.v. diuretics, dobutamine, or milrinone, plasma levels of this cytokine remained
      unchanged. Plasma TNF alpha in CHF patients measured in recovery (1 week after
      hospital discharge) was 5.1 +/- 1.2 pg/mL (range, 1.0 to 9.9 pg/mL) and 3.9 +/-
      0.8 pg/mL (range, 0.5 to 8.7 pg/mL) in groups A and B, respectively. CONCLUSION:
      These findings suggest that although noncachectic patients with chronic heart
      failure who suffer acute decompensation elaborate significantly higher
      circulating levels of TNF alpha compared with healthy control subjects, no
      significant reduction or alteration in circulating TNF alpha is noted in the
      short-term follow-up despite clinical improvement.

PMID- 8874258
TI  - The characteristics of the thrombi of the lower limbs, as detected by ultrasonic
      scanning, do not predict pulmonary embolism.
AB  - OBJECTIVE: To evaluate whether pulmonary embolism (PE), as detected by perfusion
      lung scan, could be predicted by the ultrasonic (US) characteristics of the
      thrombi in patients with deep venous thrombosis (DVT) of the lower limbs.
      PATIENTS: Ninety-three consecutive patients with DVT and no symptoms of lung
      involvement (52 men, 41 women; mean age, 67 +/- 17 years). MEASUREMENTS AND
      RESULTS: The degree of thrombotic involvement of the lower limbs was assessed
      using a US score system ranging from 1 (indicating a subsegmental, nonocclusive
      thrombus) to 16 (massive, occlusive). According to the echographic and color
      Doppler features, the thrombi were classified in terms of echoreflectivity,
      adhesiveness to the vein wall, and organization. The diagnosis of PE (PIOPED
      criteria) was highly probable in 46% of the patients, intermediate in 15%, low in
      8%, and very low/normal in 31%. No correlations were found between the lung scan
      findings on one side and the venous scoring system or the US features of the
      thrombi on the other side. CONCLUSIONS: While confirming that the prevalence of
      PE in patients with DVT is elevated, we failed to define a subgroup of patients
      at higher risk. Our data imply that lung scan should be used extensively for the
      detection of silent PE and that anticoagulation should not be graded on US
      findings.

PMID- 8874259
TI  - Thromboembolism following cardioversion of "common" atrial flutter. Risk factors
      and limitations of transesophageal echocardiography.
AB  - Based on multiple recent studies, anticoagulant therapy is recommended prior to
      elective cardioversion for patients with atrial fibrillation of more than 24 h
      duration. The value of anticoagulation in patients with atrial flutter, however,
      is less well established. Published recommendations for pericardioversion
      anticoagulation of atrial fibrillation often do not extend to patients with
      atrial flutter. We evaluated the risk of thromboembolism in our patient
      population undergoing cardioversion for atrial flutter. Over a period of 30
      months, clinically indicated electrical cardioversions were performed in 41
      patients with "common" atrial flutter. Sixteen of these patients underwent
      transesophageal echocardiograms immediately prior to cardioversion to exclude a
      left atrial thrombus. Three of the 41 patients with atrial flutter developed
      neurologic ischemic syndromes within 48 h of elective cardioversion. All three
      patients who developed ischemic neurologic complications had undergone
      transesophageal echocardiography immediately prior to cardioversion and did not
      have any evidence of left atrial clot. One patient had cardiomyopathy and the
      other two had left ventricular hypertrophy. Thus, electrical cardioversion
      without anticoagulation in patients with atrial flutter and associated heart
      disease is associated with a risk of thromboembolic events. A normal
      transesophageal echocardiogram is of doubtful value in prevention of
      thromboembolic complications.

PMID- 8874260
TI  - Is it possible to differentiate malignant mediastinal nodes from benign nodes by
      size? Reevaluation by CT, transesophageal echocardiography, and nodal specimen.
AB  - STUDY OBJECTIVE: To reevaluate whether it is possible to reliably differentiate
      malignant mediastinal lymph nodes from benign nodes by size, and to determine the
      frequency of metastases to normal-sized mediastinal lymph nodes that directly
      affects the sensitivity for detecting malignant mediastinal lymph nodes (N2
      nodes) on CT. DESIGN: Prospective study of patients with non-small cell lung
      cancer. SETTING: Department of Radiology and First Department of Surgery,
      Yamaguchi University School of Medicine. PATIENTS: We examined 40 patients with
      non-small cell lung cancer, who underwent thoracotomy because of operable stage
      (stage I, II, IIIA) in preoperative staging, using CT and transesophageal
      echocardiography (TEE). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Lymph
      nodes 10 mm or greater in short-axis diameter on CT and TEE were considered
      abnormal. Furthermore, lymph node size was measured by TEE and nodal specimens in
      long- and short-axis diameter in each patient. Two hundred eight mediastinal
      lymph nodes were dissected and N2 nodes were present in 28% of patients (11/40);
      in 7 of these 11 patients (64%), mediastinal lymph node metastases were
      misdiagnosed on CT because of normal-sized N2 nodes. Furthermore, in 73% of N2
      nodes, nodal size was normal on TEE. There were no significant difference in both
      diameters between malignant mediastinal lymph nodes and benign nodes on TEE and
      nodal specimens. CONCLUSIONS: It is not possible to reliably differentiate
      malignant mediastinal nodes from benign nodes by size alone, and we should be
      aware of high frequency of normal-sized N2 nodes in patients with operable stage
      of lung cancer.

PMID- 8874261
TI  - Postural variations of pulmonary diffusing capacity in insulin-dependent diabetes
      mellitus.
AB  - STUDY OBJECTIVE: To assess whether posture-related changes of diffusing capacity
      could be considered as an early sensitive marker of pulmonary abnormalities in
      patients with insulin-dependent diabetes mellitus (IDDM) and whether the postural
      variations of pulmonary capillary blood volume (Vc) could reflect the lung
      capillary damage that characterizes the diabetic microangiopathy. DESIGN: Carbon
      monoxide diffusing capacity (DCO) was measured by the single-breath method. Four
      DCO measurements, two in sitting and two in supine position, were performed in
      each subject using gas mixtures containing different oxygen concentrations.
      Membrane and capillary volume components of the diffusion capacity were
      calculated and both were expressed as absolute value and corrected by alveolar
      volume (VA). PATIENTS: Twenty IDDM patients and 20 normal subjects matched for
      age and sex were studied. MEASUREMENTS AND RESULTS: The IDDM patients showed
      normal pulmonary volumes and flows. No significant differences between the two
      groups were found for DCO, coefficient of diffusion, Vc, and pulmonary capillary
      blood volume corrected by alveolar volume in sitting position. All these indexes
      significantly increased in normal subjects but not in diabetics, by changing the
      posture of the subject from sitting to supine position. In a multivariate
      analysis, the presence of diabetes mellitus and the age of the subjects were the
      only significant predictors of Vc postural changes. CONCLUSIONS: This postural
      test, adjusted for age, could be included in a screening diagnostic procedure for
      an early assessment of pulmonary abnormalities in diabetic patients. The lack of
      Vc postural increase in diabetics could reflect the presence of a microangiopathy
      involving the pulmonary small vessels.

PMID- 8874262
TI  - Predicting ICU length of stay following single lung transplantation.
AB  - STUDY OBJECTIVE: The aim was to identify potential predictors of ICU length of
      stay (LOS) for single lung transplant patients. DESIGN: Retrospective chart
      review. SETTING: University medical center. PATIENTS: All single lung transplant
      recipients for 1992 and 1993 at our institution. RESULTS: Data were collected
      from 69 patients. The median ICU LOS was 5 days, and this was highly correlated
      with the duration of mechanical ventilation. The mean acute physiology and
      chronic health evaluation (APACHE II) score was 10. Patients with pulmonary
      hypertension had the longest ICU LOS. Similarly, patients with a measured
      transpulmonary gradient of 20 mm Hg or less had a significantly shorter ICU LOS.
      Patients with an immediate postoperative PaO2/fraction of inspired oxygen (FIo2)
      ratio greater than 200 mm Hg and a flow mismatch between the two lungs of 30% or
      less also had a significantly shorter ICU LOS. Positive and negative predictive
      values for the immediate postoperative PaO2/FIo2 ratio of 200 mm Hg or less were
      77% for an ICU LOS greater than 5 days, and the calculated receiver operating
      characteristic (ROC) curve area was 0.74. CONCLUSION: Overall, the immediate
      postoperative PaO2/FIo2 ratio of 200 mm Hg or less had the best positive and
      negative predictive values as well as the highest ROC curve area for predicting
      an ICU LOS greater than 5 days.

PMID- 8874263
TI  - Predicting eventual success or failure to wean in patients receiving long-term
      mechanical ventilation.
AB  - PURPOSE: To determine if the ultimate ability of a long-term ventilated patient
      to wean can be predicted at the time of his or her admission to a long-term
      ventilator unit. DESIGN: Two-phased prospective study. SETTING: Long-term
      ventilator facility, university-affiliated. SUBJECTS: Adults ventilated for an
      average of 3 weeks, who did not have sepsis and who did not have chest tubes or
      progressive neurologic impairment. INTERVENTIONS: On admission to the long-term
      ventilator unit, historic factors, ventilator history, and the following
      laboratory and metabolic tests were obtained: electrolytes, serum calcium,
      magnesium, and phosphorus, WBC, hemoglobin, albumin, total protein, transferrin,
      oxygen consumption, carbon dioxide production, respiratory quotient, and dead
      space/tidal volume. The patients were then placed in a weaning protocol utilizing
      increasing duration of pressure support ventilation during the day with complete
      rest at night. Forty-two days after enrollment in the study, representing three
      times the duration of the weaning protocol, the patients who successfully weaned
      were compared to those who remained ventilator dependent (n = 20). Patients who
      died or were transferred to another institution were excluded from this phase of
      the study, because we were trying to develop parameters that would be predictive
      of successful weaning. A parameter was considered to be predictive, and retained
      for the scoring system, if it produced at most 15% false-positives and false
      negatives. A score of 0 was then assigned to the threshold value that produced no
      false-positives; 2 to the threshold value that produced no false-negatives and 1
      to the intermediate values. The scoring system was then applied to a new
      prospective group of patients (n = 72). MEASUREMENTS AND MAIN RESULTS: Of all the
      parameters evaluated, only the following satisfied the false-positive and false
      negative requirements; static compliance, airway resistance, dead space to tidal
      volume ratio, PaCO2, and frequency/tidal volume. Applying these, in the scoring
      system, to the initial group of patients, demonstrated that a score greater than
      3 was associated with failure to wean; a score less than 3 was associated with
      successful weaning, and a score of 3 was not predictive. Using these thresholds,
      the data were applied to the new prospective group of patients, which again
      demonstrated that a score of greater than 3 was associated with failure to wean
      in all cases. A score less than 3 was again associated with successful weaning
      but there were two false-positives. The sensitivity, specificity, and positive
      predictive and negative predictive values for the scoring system were 1.0, 0.91,
      0.83, and 1.0, respectively. None of the individual parameters included in the
      scoring system demonstrated equivalent statistical results. All but two of the
      patients who died prior to finishing the weaning period had weaning scores, which
      suggested that they would not be successfully weaned. CONCLUSIONS: Parameters
      that are generally available, when combined into a scoring system, can predict at
      the time of admission to a long-term ventilator unit, in most cases, whether a
      patient will eventually wean. The scoring system resulted in no false-negatives
      and an acceptable number of false-positives. None of the individual parameters
      were as reliable as the scoring system as a whole.

PMID- 8874264
TI  - Diagnosis and treatment of ventilator-associated pneumonia--impact on survival. A
      decision analysis.
AB  - STUDY OBJECTIVE: To determine the impact of antibiotic treatment of ventilator
      associated pneumonia (VAP) on survival. DESIGN: Decision analysis. PATIENTS: A
      hypothetical cohort of immunocompetent patients receiving mechanical ventilation
      who have suspected bacterial pneumonia. The analysis was performed separately for
      the following diagnostic techniques: clinical criteria, bronchoscopic protected
      specimen brush (PSB), and nonbronchoscopic protected BAL (pBAL). Additional
      factors accounted for in the analysis included the presence or absence of prior
      antibiotic use, mortality of antibiotic-treated and untreated pneumonia,
      mortality attributable to VAP, development of antibiotic resistance, and
      mortality due to adverse drug reactions. MEASUREMENTS AND RESULTS: The overall
      survival of patients who receive antibiotic therapy was compared to survival if
      antibiotic therapy had been withheld. Antibiotic treatment of clinically
      diagnosed VAP was associated with lower overall survival than withholding
      treatment. Antibiotic treatment of VAP diagnosed by invasive (PSB) or semi
      invasive (pBAL) techniques was associated with better survival than withholding
      treatment, although withholding antibiotic therapy was favored as the mortality
      rate of antibiotic-treated VAP approached 70%. CONCLUSIONS: Invasive or semi
      invasive diagnostic techniques should be used to diagnose VAP, guide therapy, and
      thereby potentially improve survival. A prospective, randomized trial assessing
      outcome according to diagnostic technique is needed.

PMID- 8874265
TI  - Association between reduced cuff leak volume and postextubation stridor.
AB  - STUDY OBJECTIVE: Laryngotracheal injury or edema in the setting of intubation may
      narrow the upper airway and predispose toward postextubation stridor. The
      presence or absence of an audible airleak when the sealing balloon cuff of the
      endotracheal tube is deflated has been demonstrated to be a marker of
      laryngotracheal edema in high-risk patients. We hypothesized that (1) the volume
      of the cuff leak can be quantified in a general medical ICU population, and (2)
      the cuff leak volume can be correlated with likelihood of postextubation stridor.
      METHODS: Within 24 h of both the initiation and termination of mechanical
      ventilation, the cuff leak volume, defined as the difference between the
      inspiratory tidal volume and the averaged expiratory tidal volume while the cuff
      around the endotracheal tube was deflated, was recorded. RESULTS: In 100
      consecutive intubations, the preextubation cuff leak volume was 349 +/- 163 mL
      [mean +/- SD]). Overall, 6% of extubations were accompanied by postextubation
      stridor. The mean cuff leak volume measured within 24 h of planned extubation was
      significantly lower in those who subsequently developed stridor in comparison to
      those who did not (180 +/- 157 mL vs 360 +/- 157 mL; p = 0.012). The positive
      predictive value for postextubation stridor in the setting of a cuff leak less
      than 110 mL was 0.80, the predictive value for absence of postextubation stridor
      with a cuff leak volume greater than 110 mL was 0.98, and the specificity of the
      test was 0.99. No other demographic factors or indexes related to mechanical
      ventilation were significantly different between the two groups. CONCLUSIONS: A
      reduced cuff leak volume prior to extubation identifies a population at increased
      risk for postextubation stridor.

PMID- 8874266
TI  - Inhaled nitric oxide selectively decreases pulmonary artery pressure and
      pulmonary vascular resistance following acute massive pulmonary microembolism in
      piglets.
AB  - Acute massive pulmonary embolism increases pulmonary artery pressure (PAP) and
      pulmonary vascular resistance (PVR), which may lead to early right ventricular
      failure and subsequent cardiocirculatory deterioration. Inhaled nitric oxide (NO)
      selectively dilates pulmonary vessels in vivo. Thus, inhaled NO may be useful in
      preventing cardiocirculatory deterioration following pulmonary embolism. We
      investigated the effects of inhaled NO in the acute phase of massive pulmonary
      microembolism in 10 anesthetized and mechanically ventilated piglets (body
      weight, 18 +/- 2 kg). Microspheres of 300-microns diameter were injected i.v. in
      an amount sufficient to initially increase mean PAP to 45 mm Hg. Forty-five
      minutes after pulmonary embolization, the pretreatment control values were
      recorded. Thereafter, the piglets inhaled 40 ppm NO, and subsequently 80 ppm NO.
      When 40 ppm NO was inhaled, there was a significant decrease in systolic PAP (
      10.3%; 44.5 +/- 2.2 to 39.9 +/- 2.4 mm Hg; p < 0.05) and mean PAP (-9.4%; 32.9 +/
      1.3 to 29.8 +/- 1.3 mm Hg; p < 0.05). PVR was changed by -13.6% (p = 0.07).
      Administration of 80 ppm NO resulted in a significant decrease in systolic PAP (
      12.6%; to 38.9 +/- 1.9 mm Hg; p < 0.05), mean PAP (-11.9%; to 29.0 +/- 1.4 mm Hg;
      p < 0.05), and PVR (-19.4%; p < 0.05) compared with pretreatment values.
      Discontinuation of NO inhalation was associated with an immediate return to
      pretreatment values. Systemic hemodynamics and the arterial and mixed venous
      oxygen concentrations remained unchanged. We conclude that inhaled NO following
      acute massive pulmonary microembolism selectively decreases PAP and PVR without
      influencing systemic hemodynamics in piglets.

PMID- 8874267
TI  - Treatment of mucociliary dysfunction.

PMID- 8874268
TI  - Corticosteroids and the treatment of idiopathic pulmonary fibrosis. Past,
      present, and future.

PMID- 8874269
TI  - Economic aspects of lung volume reduction surgery.
AB  - OBJECTIVE: To investigate the economics of lung volume reduction surgery. DESIGN:
      Medical center and physician charges obtained from billing records. SETTING:
      Academic health center. PATIENTS: Twenty-three consecutive patients undergoing
      lung volume reduction surgery at a single institution who were discharged from
      the hospital prior to November 1, 1995. OUTCOME MEASURES: Length of hospital
      stay, mortality, medical center charges and professional fees, and sponsor
      reimbursement. RESULTS: Median hospital stay was 8.0 days and there were no
      deaths. The median charge was $26,669 (range, $20,032 to $75,561) of which 73%
      was for medical center services and 27% was for physician services. Fees for
      medical center rooms and operating suite time accounted for 71% of medical center
      charges. Charges by surgeons and anesthesiologists accounted for 77% of
      professional fees. Total charges were directly related to length of stay (r2 =
      0.95). Median reimbursement for medical center services was $22,264 (114%; range,
      $13,333 to $123,362) and for physician services was $2,783 (34%; range, $2,597 to
      $11,265), resulting in a median total reimbursement that represented 94% of total
      charges. The median reimbursement-to-cost ratio was 1.22, compared with 1.05 for
      all medical services in fiscal year 1995. CONCLUSIONS: These data must now be
      assessed relative to outcomes such as quality of life, patient function, and long
      term survival to determine cost-effectiveness of lung volume reduction surgery.

PMID- 8874270
TI  - NIDA conference report on cardiopulmonary complications of "crack" cocaine use.
      Clinical manifestations and pathophysiology.

PMID- 8874271
TI  - The pharyngeal critical pressure. The whys and hows of using nasal continuous
      positive airway pressure diagnostically.

PMID- 8874272
TI  - Atrial fibrillation. Problems in Management.

PMID- 8874273
TI  - En bloc minimal laser resection for T3-chest wall lung cancer in patients with
      poor pulmonary function.
AB  - OBJECTIVE: To analyze the value of en bloc minimal laser resection in patients
      with marginal function with non-small cell lung cancer invading the chest wall.
      DESIGN: Retrospective study from March 1987 to December 1993. SETTING: University
      teaching hospital. PATIENTS: Study group consists of 10 patients with impaired
      pulmonary function (FEV1 < or = 1.3 L and forced expiratory flow between 25% and
      75% < or = 0.8 L/s) operated on for lung cancer invading the chest wall. There
      were 7 men and 3 women; ages ranged between 51 and 77 years (mean, 66.2 years).
      None of the patients had tumors greater than 3 cm or involving the first 2 ribs
      as well as clinical N2 or T4 disease. INTERVENTIONS: All patients underwent en
      bloc chest wall combined with minimal resection. Parenchyma dissection was
      accomplished by Nd:YAG laser encompassing the lesion at distance of 2.0 cm. The
      median number of ribs resected was 1.6 and no patients required chest wall
      reconstruction. Local postoperative radiation therapy beginning within 1 month
      after resection was always performed. RESULTS: Tumor resection was considered
      complete in every case. Four patients had adenocarcinoma, three had squamous cell
      carcinoma, and three had large cell carcinoma. Currently, 7 patients had NO, 2
      had N1, and 1 had N2 disease. There was no perioperative mortality. Postoperative
      complications were prolonged air leak (n = 2) and atelectasis (n = 1). At the
      present moment, 6 patients are alive, 5 of whom are free from tumor, 2 with a
      follow-up longer than 5 years. Three patients died: 2 from disseminated disease,
      after 47 months and 32 months, respectively, and the third at 27 months from
      another cause. One patient was unavailable for follow-up. Only 1 patient had a
      local recurrence, 15 months later, and he underwent a new, successful, limited
      resection. CONCLUSIONS: These findings suggest that en bloc minimal laser
      resection can offer an acceptable risk/benefit ratio in the case of patients who
      cannot tolerate a lobectomy.

PMID- 8874274
TI  - Calcified cardiac lesion.

PMID- 8874275
TI  - Chronic mild dyspnea on exertion and diffuse alveolar infiltrates in a 37-year
      old man.

PMID- 8874276
TI  - Pneumothorax ex vacuo.
AB  - Pneumothorax ex vacuo is a little-known complication of lobar collapse. In this
      condition, acute bronchial obstruction from mucous plugs, aspirated foreign
      bodies, or malpositioned endotracheal tubes causes acute lobar collapse and a
      marked increase in negative intrapleural pressure around the collapsed lobe. As a
      result, gas is drawn into the pleural space around the collapsed lobe while the
      seal between the visceral and parietal pleura of the adjacent lobe or lobes
      remains intact. The pneumothorax spontaneously resolves when the bronchial
      obstruction is relieved and the lobe reexpands. Recognition of pneumothorax ex
      vacuo is crucial in directing treatment to relieve the bronchial obstruction
      rather than inserting a chest tube into the pleural space.

PMID- 8874277
TI  - Kyphosis secondary to tuberculosis osteomyelitis as a cause of ventilatory
      failure. Clinical features, mechanisms, and management.
AB  - STUDY OBJECTIVES: To investigate the relationship of thoracic kyphosis following
      tuberculosis to the development of ventilatory failure and to assess the efficacy
      on nocturnal noninvasive ventilatory support. DESIGN: Retrospective consecutive
      case series with crossover from a phase without noninvasive ventilatory support
      to a phase with this treatment. SETTING: The Respiratory Support and Sleep
      Centre, Papworth, Hospital, Cambridge, England. PATIENTS: Seven patients with
      thoracic kyphosis following tuberculous osteomyelitis which had been contracted
      by the age of 4 years were studied. Their mean age was 53 (SD 7.1) years and the
      mean angle of kyphosis was 113.60. All patients were in ventilatory failure.
      INTERVENTIONS: The patients were treated with nocturnal noninvasive ventilation
      with either an individually constructed cuirass shell and a negative pressure
      pump or nasal intermittent positive pressure ventilation using a volume preset
      ventilator. MEASUREMENT AND RESULTS: Each patient underwent an initial clinical
      assessment along with radiologic studies of the spine, pulmonary function tests,
      daytime arterial blood gas tensions, and overnight recordings of arterial
      saturation, and transcutaneous carbon dioxide tension. They were reassessed in
      detail at a mean of 5 years after starting ventilatory support. Symptoms, vital
      capacity, daytime carbon dioxide tension, and overnight oximetry had all improved
      following treatment. Temporary withdrawal of ventilatory support led to severe
      sleep fragmentation in four patients and the appearance of central apneas and
      hypopneas in the other three. Six of the 7 patients were alive at a mean of 5.7
      years after starting nocturnal ventilation. CONCLUSION: These results show that
      ventilatory failure may develop, after an interval of many years, in patients
      with a severe thoracic kyphosis due to tuberculosis in childhood. Noninvasive
      nocturnal ventilatory support can control the symptoms of ventilatory failure,
      improve the physiologic abnormalities, and is associated with prolonged survival.

PMID- 8874278
TI  - Use of bronchial blocker to improve gas exchange in respiratory failure and
      differential lung disease.
AB  - The use of bronchial blocker to optimize gas exchange in a patient with marked
      differential lung disease is reported. This technique proved to be a useful
      alternative in an ICU setting to independent lung ventilation.

PMID- 8874279
TI  - Chronic aortic dissection presenting as a prolonged febrile disease and arterial
      embolization.
AB  - Aortic dissection most often is an acute event dominated by excruciating pain and
      other symptoms which suggest the diagnosis. Our report and a review of the
      medical literature demonstrate that chronic aortic dissection may, rarely,
      present as a prolonged febrile illness, with night sweats, weight loss, pleural
      effusion, and little or no pain. These symptoms may be associated with a markedly
      elevated erythrocyte sedimentation rate (ESR), anemia of chronic disease, and
      hyperglobulinemia. Awareness of this unusual presentation, a high index of
      suspicion, and confirmation by an appropriate imagine technique (CT or MRI of the
      chest or transesophageal echocardiography have a very high sensitivity) will
      result in earlier diagnosis and better patient outcome.

PMID- 8874280
TI  - Retreatment of recurrent invasive thymoma with platinum, doxorubicin, and
      cyclophosphamide.
AB  - Invasive thymoma recently has been shown to be sensitive to combination
      chemotherapy and in some cases to be relatively indolent. Two cases of extensive
      thymoma which responded to primary treatment with a combination of a platinum
      compound (carboplatin or cisplatin), doxorubicin (Adriamycin), and
      cyclophosphamide (or PAC) are described. Tumor progression occurred 14 (case 1)
      and 60 months (case 2) after completion of initial PAC therapy and was treated
      with the same regimen resulting in a second remission, which lasted 6 months in
      case 1 and is continuing at 8 months in case 2. Similar reports of secondary
      responses using the same chemotherapy have been described in breast, lung, and
      ovarian cancers, as well as in Hodgkin's lymphomas. Our observations suggest that
      retreatment with the same platinum-based regimen should be considered in patients
      who have progressive thymomas following a previous chemotherapeutic response and
      a disease-free interval of greater than 12 months.

PMID- 8874281
TI  - Chest pain in an aspirin-sensitive asthmatic patient. Eosinophilic esophagitis
      causing esophageal dysmotility.
AB  - We describe a case of eosinophilic esophagitis in a 38-year-old man with aspirin
      sensitivity asthma which presented as noncardiac chest pain. Manometric
      measurements demonstrated tertiary contractions. Biopsies showed a dense
      eosinophilic infiltrate in the mucosa. There was no response to therapy for
      reflux. Symptoms quickly resolved with corticosteroid therapy. Subsequent
      manometric values recorded after corticosteroid therapy showed resolution of the
      dysmotility. Biopsies showed normal mucosa. Adult asthmatic subjects with
      noncardiac chest pain should receive further investigation if reflux therapy
      fails to resolve the symptoms.

PMID- 8874282
TI  - Upper airway obstruction secondary to acinic cell carcinoma of the trachea. Use
      of Nd:YAG laser.
AB  - Comprising 1 to 4% of all tumors and 7 to 15% of malignant neoplasms of the major
      salivary glands, acinic cell carcinoma (ACC) rarely occurs in the respiratory
      tract. There has been only one case of ACC of the trachea previously reported in
      the medical literature. A second case of ACC of the trachea associated with upper
      airway obstruction and its management by Nd: YAG laser and surgical resection is
      reported.

PMID- 8874283
TI  - Nasal-continuous positive airway pressure in the treatment of near-drowning in
      freshwater.
AB  - In patients who have experienced near-drowning, hypoxemia is the major clinical
      consequence. We report two cases of patients who have experienced near-drowning
      in freshwater who were successfully treated with nasal-continuous positive airway
      pressure (N-CPAP) plus oxygen therapy. Both patients presented a radiographic
      appearance of bilateral pulmonary edema. We suggest the use of N-CPAP as an
      easier and less costly alternative to tracheal intubation for treating near
      drowning in patients who are breathing spontaneously and who have not experienced
      loss of consciousness.

PMID- 8874284
TI  - Resecting pulmonary cancer of a colorectal origin.

PMID- 8874285
TI  - Blunt cardiac injury.

PMID- 8874286
TI  - Local anesthesia with thoracoscopic talc poudrage pleurodesis.

PMID- 8874288
TI  - Exercise-induced bronchoconstriction in healthy athletes.

PMID- 8874289
TI  - Myasthenia gravis and upper airway dysfunction.

PMID- 8874290
TI  - Isotretinoin-related eosinophilic pleural effusion.

PMID- 8874287
TI  - Local anesthesia with thoracoscopic talc poudrage pleurodesis.

PMID- 8874291
TI  - Tuberculosis patients. Who should we isolate?

PMID- 8874293
TI  - Risks of home oxygen therapy for cigarette smokers.

PMID- 8874292
TI  - Intractable hiccups. Consider nebulized lidocaine.

PMID- 8874294
TI  - Steroids for anything that swells: dexamethasone and postextubation airway
      obstruction.

PMID- 8874295
TI  - Economic impact of prolonged neuromuscular weakness complicating neuromuscular
      blockade in the intensive care unit.

PMID- 8874296
TI  - Starling resistor effects on pulmonary artery occlusion pressure in endotoxin
      shock provide inaccuracies in left ventricular compliance assessments.
AB  - OBJECTIVES: Assessment of left ventricular preload and left ventricular
      compliance changes in septic shock using pulmonary artery occlusion pressure
      (PAOP) presumes that this pressure accurately reflects left heart filling
      pressure. We tested the hypothesis that Starling resistor forces render PAOP
      inaccurate as an index of left heart filling pressure, resulting in misleading
      assessments of left ventricular compliance changes. DESIGN: Prospective,
      randomized, controlled study. SETTING: Large-animal research laboratory at a
      university. SUBJECTS: Fourteen anesthetized domestic pigs weighing 20 to 25 kg.
      INTERVENTIONS: Pulmonary artery flotation catheters and systemic arterial
      catheters were placed via right cervical vessels. The left atrium was directly
      catheterized for left atrial pressure measurements. Left ventricular end
      diastolic diameter was measured using sonomicrometry. Other measured or
      calculated variables were mean arterial pressure, mean pulmonary arterial
      pressure, PAOP, pulmonary capillary pressure, and pulmonary arterial and venous
      resistances. Pigs received endotoxin (0.5 mg/kg i.v. over 30 mins), or an
      equivalent volume of saline. At t = 60 mins, pigs were resuscitated with lactated
      Ringer's solution (40 mL/kg over 30 mins). Measurements were taken before and
      after endotoxin administration, and immediately and 30 mins after lactated
      Ringer's solution administration. Data were analyzed by two-way analysis of
      variance (p < or = .05). MEASUREMENTS AND MAIN RESULTS: PAOP, mean pulmonary
      arterial pressure, and pulmonary capillary pressure increased after endotoxin
      infusion, while left atrial pressure and left ventricular end-diastolic diameter
      decreased. Left atrial pressure and left ventricular end-diastolic diameter
      returned to baseline immediately after lactated Ringer's solution administration,
      while PAOP remained increased. Pulmonary arterial resistance and pulmonary venous
      resistance increased after endotoxin administration, with pulmonary venous
      resistance showing the greater percent increase. Pulmonary venous resistance
      decreased transiently immediately after lactated Ringer's solution
      administration. These changes were not observed in the control group.
      Accordingly, comparisons of PAOP vs. left ventricular end-diastolic diameter, and
      left atrial pressure vs. left ventricular end-diastolic diameter yielded
      divergent results. CONCLUSIONS: The dissociation between PAOP and left atrial
      pressure, while left ventricular and -diastolic diameter (preload volume)
      decreased, and changes in pulmonary venous resistance, are strong evidence for
      Starling resistor forces (venocompression) rather than active venoconstriction.
      These data indicate that PAOP overestimates left atrial pressure during endotoxin
      shock, making it an inaccurate index of left ventricular preload. This
      overestimation can cause misleading assessments of left ventricular compliance.

PMID- 8874297
TI  - Planning patient services for intermediate care units: insights based on care for
      intensive care unit low-risk monitor admissions.
AB  - OBJECTIVE: To describe the technology and nursing services that would be required
      to care for intensive care unit (ICU) low-risk monitor admissions in an
      intermediate unit. DESIGN: Prospective, multicenter, inception cohort analysis.
      SETTING: Forty U.S. hospitals with > 200 beds, including 26 hospitals that were
      randomly selected and 14 that volunteered for the study. PATIENTS: A sample of
      8,040 ICU patients admitted to the ICU for monitoring, who received no active
      life-support treatment on ICU day 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Demographic, physiologic, and treatment information were obtained during
      ICU days 1 to 7. A previously validated multivariate equation was used to
      identify 6,180 monitor admissions at low (< 10%) risk for receiving active
      treatment during their entire ICU stay. We used daily Therapeutic intervention
      Scoring System (TISS) data to identify the equipment, type and amount of nursing
      care, and the types of active treatment that would have been used had these ICU
      patients been admitted to an intermediate care unit. Mean day-1 ICU TISS scores
      were as follows: 16.4 for all patients; 18.3 for surgical patients; and 13.5 for
      medical admissions. Concentrated nursing care accounted for 89% and technologic
      monitoring for 11% of day-1 TISS points. Surgical admissions had a 2.8-day mean
      ICU length of stay and received an average of 16.5 TISS points per patient per
      day. Medical admissions had a 2.7-day mean ICU length of stay and received an
      average of 12.3 TISS points per patient per day. Subsequent active life-support
      therapy was received by 4.4% of these ICU low-risk monitor admissions.
      CONCLUSIONS: The services received by ICU low-risk monitor admissions provide
      insight regarding the equipment and nursing care that might be required, and the
      kinds of emergencies that might occur, if these patients were cared for in
      medical and surgical intermediate care units. Our data suggest that if ICU low
      risk monitor patients were admitted to an intermediate care unit, they would
      mainly require concentrated nursing care (nurse/patient ratio of 1:3 to 1:4) and
      limited technologic monitoring.

PMID- 8874298
TI  - A comparison of risks and outcomes for patients with organ system failure: 1982
      1990.
AB  - OBJECTIVES: To compare the outcomes for patients with one or more organ system
      failures treated in 1988 to 1990 with those outcomes from 1979 to 1982; to
      document risk factors for developing organ system failure; and investigate the
      relationship of these factors to hospital survival. DESIGN: Prospective,
      multicenter, inception cohort analysis. SETTING: Sixty intensive care units
      (ICUs) at 53 U.S. hospitals. PATIENTS: A total of 17,440 ICU admissions treated
      in 1988 to 1990 and 5,677 ICU admissions treated in 1979 to 1982. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: At the time of organ system failure,
      patients were classified by demographic, physiologic, and diagnostic information.
      The type and number of organ system failures and physiologic responses were
      recorded for < or = 7 days of ICU treatment, and all patients were followed for
      status at hospital discharge. Hospital survival and the prognostic value of
      assessing the number of organ system failures were compared with risk assessment,
      based on use of a prognostic scoring system that estimated the patient's
      probability of hospital mortality. The incidence of organ system failure (48%)
      among patients treated in 1988 to 1990 was similar (44%) to the occurrence rate
      in patients in 1979 to 1982; and an identical proportion (14%) developed multiple
      organ system failure. There was a significant (p < .0003) improvement in hospital
      mortality for patients with three or more organ system failures on day 4 or later
      of organ system failure. However, overall hospital mortality rates from multiple
      organ system failure were not different over this 8-yr period. The most important
      predictor of hospital mortality was the severity of physiologic disturbance on
      the initial day of failure. Discrimination of patients by risk of hospital
      mortality was better using the prognostic scoring system on day 1 of organ system
      failure (receiver operating characteristic curve = 0.88) than using a model based
      on the number of organ system failures (receiver operating characteristic curve =
      0.68). CONCLUSIONS: Organ system failure remains a major contributor to death in
      patients in ICUs. The incidence and overall outcome have not significantly
      changed over the past 8 yrs, but there has been significant improvement in
      survival for patients with persistent severe organ system failure. A continuous
      measure of individual patient severity of illness is a more sensitive and
      accurate method for describing patients and estimating outcome than counting the
      number of organ system failures.

PMID- 8874299
TI  - A comparison of the Acute Physiology and Chronic Health Evaluation (APACHE) II
      score and the Trauma-Injury Severity Score (TRISS) for outcome assessment in
      intensive care unit trauma patients.
AB  - OBJECTIVE: To assess the ability of the Acute Physiology and Chronic Health
      Evaluation (APACHE II) system and Trauma-Injury Severity Scoring (TRISS) system
      in predicting group mortality in intensive care unit (ICU) trauma patients.
      DESIGN: Prospective study. SETTING: A Canadian adult trauma tertiary referral
      hospital. PATIENTS: Consecutive trauma patients admitted to the medical-surgical
      ICU or the neurosurgical ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS:
      For each patient, demographic data, mechanism of injury, and surgical status were
      collected. Revised Trauma Scores and Injury Severity Scores were calculated from
      emergency room and operative data. The APACHE II score was calculated based on
      the data from the first 24 hrs of ICU admission. The probability of death was
      calculated for each patient based on the APACHE II and TRISS equations. The
      ability to predict group mortality for APACHE II and TRISS was assessed by
      receiver operating characteristic curve analysis, two by two decision matrices,
      and calibration curve analysis. Four hundred seventy trauma patients were
      admitted to the ICU. Sixty-three (13%) patients died and 407 (87%) survived.
      There were significant differences between survivors and nonsurvivors in age,
      Glasgow Coma Scale, Revised Trauma Score, Injury Severity Score, and APACHE II
      score. By receiver operating characteristic curve analysis, the areas under the
      curves (+/- SEM) of APACHE II and TRISS were 0.92 +/- 0.02 and 0.89 +/- 0.02,
      respectively. Using two by two decision matrices with a decision criterion of
      0.5, the sensitivities, specificities, and percentages correctly classified were
      50.8%, 97.3%, and 91.1%, respectively, for APACHE II, and 50.8%, 97.1%, and
      90.9%, respectively, for TRISS. From the calibration curves, the r2 value was .93
      (p = .0001) for APACHE II and .67 (p = .004) for TRISS. CONCLUSIONS: Both APACHE
      II and TRISS scores were shown to accurately predict group mortality in ICU
      trauma patients. APACHE II and TRISS may be utilized for quality assurance in ICU
      trauma patients. However, neither APACHE II nor TRISS provides sufficient
      confidence for prediction of outcome of individual patients.

PMID- 8874300
TI  - Xanthine oxidase activity and free radical generation in patients with sepsis
      syndrome.
AB  - OBJECTIVE: To determine xanthine oxidase activity, free radical concentrations,
      and lipid peroxidation in patients with sepsis syndrome compared with noninfected
      critically ill patients. DESIGN: A prospective observational study. SETTING: A
      nine-bed intensive care unit in a university teaching hospital trust. PATIENTS:
      Fourteen consecutive patients who met the established criteria for sepsis
      syndrome with multiple organ dysfunction syndrome, and ten noninfected critically
      ill patients were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Xanthine oxidase activity was increased in septic patients compared with both
      healthy volunteers (p < .01) and noninfected patients (p < .05), and was highest
      in the six patients who survived (p < .05). Lipid peroxides were increased in
      both septic patients (p < .001) and nonseptic controls (p < .001). Xanthine
      oxidase activity did not relate to the Acute Physiology and Chronic Health
      Evaluation (APACHE) II score or to the presence of organ dysfunction. The mean
      ascorbyl radical concentration (arbitrary units) determined by electron
      paramagnetic resonance following spin trapping was increased in patients compared
      with healthy subjects (p < .05). CONCLUSIONS: Patients with sepsis have xanthine
      oxidase activation, high free-radical concentrations, and evidence of free
      radical damage. The finding that xanthine oxidase activity was lower in those
      patients who died, coupled with increased lactate concentrations implies more
      severe ischemia with incomplete reperfusion resulting in less xanthine oxidase
      "wash out" into the circulation. Increased ascorbyl radical concentrations may be
      due to an increased radical generation and oxidant scavenging, but appears to be
      unrelated to xanthine oxidase activity within the circulation.

PMID- 8874301
TI  - Perioperative lymphocyte adenylyl cyclase function in the pediatric cardiac
      surgical patient.
AB  - OBJECTIVE: To examine intraoperative and postoperative lymphocyte adenylyl
      cyclase activities in children undergoing repair of congenital cardiac defects
      with hypothermic cardiopulmonary bypass. DESIGN: A prospective study. SETTING:
      Tertiary university pediatric hospital. PATIENTS: Twelve children were enrolled
      into the study to examine intraoperative lymphocyte adenylyl cyclase activities
      and 12 children were enrolled to examine postoperative lymphocyte adenylyl
      cyclase activities. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Basal
      (unstimulated), isoproterenol, and prostaglandin E-1 stimulated adenylyl cyclase
      activities, and plasma norepinephrine and epinephrine concentrations were
      measured. Intraoperative basal (unstimulated), beta-adrenergic receptor
      stimulated (in response to isoproterenol), and prostaglandin E1 (PGE1)-stimulated
      lymphocyte adenylyl cyclase activities all increased during cardiopulmonary
      bypass, then decreased immediately after cardiopulmonary bypass. In the
      postoperative group, a significant decrease in basal (unstimulated), beta
      adrenergic receptor- and PGE1-stimulated adenylyl cyclase activities were
      observed on postoperative day 1 as compared with precardiopulmonary bypass
      values. CONCLUSIONS: In the pediatric cardiac surgical patient, there was an
      intraoperative enhancement of lymphocyte adenylyl cyclase activities. This
      increase in adenylyl cyclase activities was followed by reduced lymphocyte
      adenylyl cyclase activities, including beta-adrenergic receptor desensitization,
      postoperatively, as we have previously documented in adults.

PMID- 8874303
TI  - Dexamethasone for the prevention of postextubation airway obstruction: a
      prospective, randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine whether dexamethasone prevents postextubation airway
      obstruction in young children. DESIGN: Prospective, randomized, double-blind,
      placebo-controlled study. SETTING: Pediatric intensive care unit of a university
      teaching hospital. PATIENTS: Sixty-six children, < 5 yrs of age, intubated and
      mechanically ventilated for > 48 hrs. INTERVENTIONS: Patients were randomized to
      receive intravenous dexamethasone (0.5 mg/kg, maximum dose 10 mg) or saline,
      every 6 hrs for six doses, beginning 6 to 12 hrs before elective extubation.
      MEASUREMENTS AND MAIN RESULTS: Dependent variables included the presence of
      stridor, Croup Score, and pulsus paradoxus at 10 mins, 6, 12, and 24 hrs after
      extubation; need for aerosolized racemic epinephrine and reintubation. The
      dexamethasone and placebo groups were similar in age (median 3 months [range 1 to
      57] vs. 4 months [range 1 to 59], p = .6), frequency of underlying airway
      anomalies (3/33 vs. 3/33, p = 1.0), and duration of mechanical ventilation
      (median 3.3 days [range 2.1 to 39] vs. 3.5 days [range 2.1 to 15], p = .7). The
      dexamethasone group had a lower frequency of stridor, Croup Score, and pulsus
      paradoxus measurement at 10 mins and at 6 and 12 hrs after extubation. Fewer
      dexamethasone-treated patients required epinephrine aerosol (4/31 vs. 22/32, p <
      .0001) and reintubation (0/31 vs. 7/32, p < .01). Three patients exited the study
      early-one patient in the dexamethasone group had occult gastrointestinal
      hemorrhage and one patient in each group had hypertension. CONCLUSION:
      Pretreatment with dexamethasone decreases the frequency of postextubation airway
      obstruction in children.

PMID- 8874302
TI  - Decreasing catheter-related infection and hospital costs by continuous quality
      improvement.
AB  - OBJECTIVES: a) To reduce the rate of catheter-related infection, using improved
      skin preparation and catheters impregnated with silver sulfadiazine and
      chlorhexidine; b) to decrease the number of unnecessary guidewire exchanges of
      existing catheters by substituting suspected catheter-related sepsis for fever
      alone as an indication to change an indwelling catheter; and c) to decrease the
      hospital costs associated with guidewire exchanges and new catheter insertions.
      DESIGN: Sequential, prospective, descriptive studies using a continuous quality
      management approach. SETTING: A 20-bed trauma intensive care unit at a university
      teaching hospital. PATIENTS: Patients (n = 147) admitted from July 1 to December
      31, 1992 (phase 1); 34 patients admitted in June and September 1993 (phase 2);
      and 156 patients admitted between January 1 and June 30, 1994 (phase 3).
      INTERVENTIONS: Phase 1: Proportions of catheter-related infections and catheter
      related bacteremia were compared with our prior reported results. Indications for
      guidewire exchange were analyzed, and the rate of catheter-related infection for
      each indication was derived. Phase 2: The rate of catheter-related infection was
      determined for a trial group of triple-lumen catheters impregnated with silver
      sulfadiazine and chlorhexidine. Phase 3: Four components were altered.
      Impregnated triple-lumen catheters were used instead of unprotected catheters.
      Chlorhexidine skin cleanser was substituted for povidone-iodine solution during
      initial aseptic preparation during catheter insertion and subsequent guidewire
      exchange. Suspected catheter-related sepsis was substituted for fever as an
      indication for guidewire exchange. The "safe" period (the time before considering
      changing a catheter because catheter-related sepsis was suspected) was extended
      from 2 to 4 days. MEASUREMENTS AND MAIN RESULTS: The overall rate of catheter
      related infection in phase 1 was 15% (15% for triple-lumen catheters and 16% for
      introducers). Catheters changed for site inflammation had a 46% rate of catheter
      related infection, significantly higher than for all other indications, including
      fever (p < .03). The rate of catheter-related infection was significantly (p =
      .0002) higher for catheters in place for > 10 days compared with lesser
      durations. Fever was the indication for 42% of all guidewire exchanges. In phase
      2, the catheter-related infection rate was 2% (one positive of 48 catheters),
      significantly (p = .0231) lower than the phase 1 rate. In phase 3, the overall
      rate of catheter-related infection was 8.6%, significantly (p = .0067) lower than
      the 15% rate in phase 1. The proportion of protected triple-lumen catheter
      catheter-related infections decreased significantly (p = .0024) from 15% to 6%.
      The rate of catheter-related infection for introducers was the same in both
      phases (p = .33). The days of catheterization for all catheters increased from
      4.5 +/- 2.6 to 5.4 +/- 3.6 (p < .0001). The days for triple-lumen catheters
      increased from 4.7 +/- 2.7 to 7.0 +/- 3.9 (p < .0001). For introducers, there was
      no difference in the days of catheterization. The proportion of catheters changed
      for suspected catheter-related sepsis decreased significantly (p < .0001) to 23%
      from the 42% changed for fever in phase 1. The proportion of catheter-related
      infections for catheters changed for fever was 18% in phase 1. The proportion of
      catheter-related infections for catheters changed for suspected catheter-related
      sepsis was 13% in phase 3 (p = .43). The total number of catheters used per
      patient in phase 3 was 1.9 +/- 1.4, significantly lower than the 2.6 +/- 2.7
      catheters used in phase 1 (p = .0018). The number of triple-lumen catheters
      decreased from 1.8 +/- 1.2 to 1.0 +/- 1.2 in phase 3 (p = .0001). CONCLUSIONS:
      Catheters impregnated with silver sulfadiazine and chlorhexidine had a smaller
      proportion of catheter-related infection compared with unprotected catheters.
      Fever alone as an indication for guidewire exchange resu

PMID- 8874304
TI  - Histamine release in sepsis: a prospective, controlled, clinical study.
AB  - OBJECTIVE: To determine if histamine release occurs in clinical sepsis. DESIGN:
      Prospective, controlled, clinical study. SETTING: Interdisciplinary intensive
      care unit and trauma ward. PATIENTS: Sepsis was confirmed in 20 patients (test
      group) by the criteria of the Veterans Administration Systemic Sepsis Cooperative
      Study Group (1987) and was verified by positive blood culture. In addition,
      patients were scored by the Elebute and Stoner Sepsis Score (1983), as modified
      by Dionigi et al (1985). A concomitant control group consisted of 20
      postoperative patients with non-life-threatening trauma to the extremities and
      without signs of local or systemic infection. INTERVENTIONS: Observational study.
      Blood samples were collected for determination of plasma histamine concentrations
      in both groups at the time of study entry and on five succeeding days.
      MEASUREMENTS AND MAIN RESULTS: The patients were well matched, and the groups
      were not significantly different for all criteria known to influence histamine
      release. Comparison of the median values of each group on days 1 through 5
      demonstrated significantly higher plasma histamine values in the test group on
      days 1 through 4, but these values were no longer significantly higher on day 5.
      While none of the nonseptic control patients achieved a plasma histamine
      concentration of > 1 ng/mL (the concentration of which was considered to be the
      pathologic cutoff point representing histamine release), these values (i.e., > 1
      ng/ mL) were found in nine of 20 test group patients. In the test group,
      nonsurvivors (n = 9) had significantly higher plasma histamine concentrations
      than survivors (n = 11) throughout the whole study and eight of nine nonsurvivors
      showed a plasma histamine concentration of > 1 ng/mL. Correlation of plasma
      histamine concentrations on day 1 to sepsis severity (initial Sepsis Score)
      showed that all but one patient with a combined low Sepsis Score (< 20 points)
      and histamine concentration of < 1 ng/mL survived, while all patients with a
      Sepsis Score of > 20 points and histamine release (plasma histamine concentration
      of > 1 ng/mL) died. CONCLUSION: Increased histamine concentrations were shown to
      be causally associated (contributory determinant) with sepsis.

PMID- 8874305
TI  - A comparison of venovenous and venoarterial extracorporeal membrane oxygenation
      in the treatment of neonatal respiratory failure.
AB  - OBJECTIVE: To compare the efficacy of venovenous to venoarterial bypass in an
      unselected cohort of infants with refractory cardiorespiratory failure. DESIGN:
      Retrospective cohort analysis. SETTING: Two tertiary hospitals capable of
      providing extracorporeal life support for neonates with acute respiratory
      failure. PATIENTS: All San Diego Regional Extracorporeal Membrane Oxygenation
      (ECMO) Program patients treated after the adoption of a policy which eliminated
      traditional restrictions to venovenous support. INTERVENTIONS: Venoarterial or
      venovenous extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: Fifty-four
      infants were treated with venovenous bypass; 30 were treated with venoarterial
      bypass due to unsuccessful placement of the double lumen venovenous catheter or
      inability to exclude congenital heart disease before cannulation. No patient
      required conversion from venovenous to venoarterial ECMO. There were no
      differences in birth weight, gestational age, diagnosis, or pre-ECMO condition in
      the two groups. Patients who met ECMO criteria early were more likely to be
      successfully cannulated with a double-lumen venovenous catheter. Severe
      hemodynamic compromise was present before cannulation in a comparable percentage
      of venovenous and venoarterial patients. During venovenous bypass, mean Pao2
      values were lower but remained in the normoxic range; Paco2 values, ventilatory
      setting, intravascular volume requirements, inotropic support, and mean duration
      of ECMO support were not different. The frequency rate of patient and mechanical
      complications were also comparable, except that the frequency of intravascular
      thrombosis was significantly lower in patients receiving venovenous ECMO.
      Survival, the frequency rate of chronic lung disease, and neurodevelopmental
      outcome were similar in the two groups. CONCLUSIONS: We conclude that venovenous
      ECMO using a double-lumen venovenous catheter can provide results comparable with
      venoarterial bypass without the need for carotid artery ligation in an unselected
      population of neonatal ECMO candidates. In our experience, reported
      contraindications to venovenous ECMO did not prove to be valid.

PMID- 8874306
TI  - Accuracy and reliability of noninvasive continuous finger blood pressure
      measurement in critically ill patients.
AB  - OBJECTIVE: To evaluate the accuracy and reliability of noninvasive continuous
      finger blood pressure measurement in critically ill patients. DESIGN: Prospective
      data collection. SETTING: Emergency department in a 2,000-bed hospital. PATIENTS:
      Thirty-nine patients admitted to the emergency department requiring invasive
      arterial blood pressure monitoring were enrolled to the study protocol.
      INTERVENTIONS: Continuous noninvasive blood pressure measurement was performed on
      the middle phalanx of the second and third finger, using a test instrument which
      provides continuous arterial waveform display with the use of a finger cuff.
      Invasive mean arterial blood pressure measurement was done by cannulation of the
      radial artery and direct transduction of the systemic arterial pressure waveform.
      MEASUREMENTS AND MAIN RESULTS: Three thousand one hundred eighteen pairs of
      simultaneous finger cuff and intra-arterial blood pressure measurements were
      collected in 1-min intervals from 39 patients over a total of 51.8 hrs. The
      overall discrepancy between both measurements was 0.10 mm Hg. The standard
      deviation of the differences was +/- 5.02 mm Hg. The mean bias in patients
      treated with catecholamines was 0.01 mm Hg and was not different from the bias
      observed in patients without catecholamines (mean bias: 0.23 mm Hg; p > .22).
      Whereas 95% of all comparisons between finger cuff and intra-arterial measurement
      had a discrepancy < or = +/- 10 mm Hg, 4.7% had a discrepancy between +/- 10.1 to
      15 mm Hg and 0.3% exhibited a discrepancy > +/- 15 mm Hg. In 29 (74%) patients,
      the duration of errors > 10 mm Hg was < or = 1 min. In seven (18%) patients, the
      duration of errors > 10 mm Hg was between 2 to 3 mins and in three (8%) patients,
      the errors lasted for > 3 mins. CONCLUSIONS: Our data provide a guide to the
      accuracy and reliability of noninvasive finger blood pressure measurements in
      critically ill patients. Although most test instrument measurements were
      reliable, in 8% of all patients large discrepancies (> 10 mm Hg) between both
      measurements with a duration of > 3 mins were noted. Concerning the considerable
      risk for arterial cannulation, our preliminary data demonstrate that the test
      instrument (PORTAPRES, TNO Biomedical Instrumentation Research Unit; The
      Netherlands) is an advance in noninvasive monitoring of critically ill patients
      and may be useful in most emergency clinical settings.

PMID- 8874309
TI  - Noninvasive determination of cardiac output using single breath CO2 analysis.
AB  - OBJECTIVE: To examine the utility of single breath CO2 analysis as a noninvasive
      measure of cardiac output. SETTING: An animal laboratory in a university
      affiliated medical center. DESIGN: A prospective, animal cohort study comparing
      21 parameters derived from single breath CO2 analysis with cardiac output
      determined by an ultrasonic flow probe. SUBJECTS: Six healthy adult sheep.
      METHODS: The single breath CO2 analysis station consists of a mainstream
      capnometer, a variable orifice pneumotachometer, a signal processor, and computer
      software with capability for both on- and off-line data analysis. Twenty-one
      derived components of the CO2 expirogram were evaluated as predictors of cardiac
      output. Cardiac output was manipulated by successive injections of a hydraulic
      constrictor placed around the inferior vena cava. MEASUREMENTS AND MAIN RESULTS:
      Thirty-four measurements of cardiac output were available for comparison with
      derived variables from the CO2 expirogram. Stepwise linear regression identified
      two variables that were most predictive of cardiac output: a) the angle between
      the slope lines for phase II and III of the CO2 expirogram divided by the volume
      of CO2 per breath (angle/mL CO2); and b) the slope of phase II. The multivariate
      equation was highly statistically significant and explained 94% of the variance
      (adjusted r2 = .94, p < .0001). The bias and precision of the calculated cardiac
      output were .00 and .23, respectively. The mean percent difference for the
      cardiac output estimate derived from the single breath CO2 analysis station was
      0.36%. CONCLUSIONS: Our data indicate that analysis of the CO2 expirogram can
      yield accurate information about the cardiovascular system. Specifically, two
      variables derived from a plot of expired CO2 concentration vs. expired volume
      predict changes in cardiac output in healthy adult sheep with an adjusted
      coefficient of determination of .94. Prospective application of this technology
      in the setting of lung injury and rapidly changing physiology will be essential
      in determining the clinical usefulness of the technique.

PMID- 8874307
TI  - Bedside sonographic-guided versus blind nasoenteric feeding tube placement in
      critically ill patients.
AB  - OBJECTIVE: To compare a blind manual bedside method for placing feeding tubes
      into the small bowel vs. a sonographic bedside technique in critically ill
      patients. DESIGN: Prospective study with a random sample. SETTING:
      Multidisciplinary intensive care unit in a tertiary care university hospital.
      PATIENTS: Thirty-five adult patients. All patients were hemodynamically stable,
      mechanically ventilated, and required a nasoenteric tube placement for short-term
      enteral feeding due to impaired gastric emptying. INTERVENTIONS: A well-known,
      blind, manual, bedside method for postpyloric tube placement was always attempted
      first in all cases. The technique was considered successful when a postpyloric
      location of the tip of the tube was achieved as shown by abdominal roentgenogram.
      However, if after 30 mins we failed to enter the small bowel, a radiologist
      attempted a sonographic bedside technique for postpyloric tube insertion.
      Finally, when the feeding tube was in place, before starting enteral nutrition, a
      nasogastric tube was inserted into the stomach. MEASUREMENTS AND MAIN RESULTS:
      The blind manual method was successful in nine (25.7%) of the 35 patients and the
      final location of these feeding tubes was the proximal jejunum. The average time
      for placement of the feeding tubes with this manual technique was 13.9 +/- 7.4
      mins (range 5 to 30). The sonographic technique was successful in 22 (84.6%) of
      the remaining patients and the final location of the feeding tubes was three
      (11%) tubes in the second portion of the duodenum, eight (31%) tubes in the third
      portion of the duodenum, and 11 (42%) tubes in the proximal jejunum. The average
      time for placement with the sonographic technique was 18.3 +/- 8.2 mins (range 5
      to 35). The pyloric outlet was sonographically akinetic or severely hypokinetic
      in 13 patients, and in four of them, we were unable to achieve postpyloric tube
      placement. In these four patients, the tubes were subsequently placed by
      endoscopy. CONCLUSIONS: The sonographic bedside technique for placing feeding
      tubes into the small bowel in critically III patients has a success rate of 84.6%
      (confidence interval 71% to 98%) after the failure of the blind bedside manual
      method, proving that the former is significantly more successful. This
      sonographic technique facilitates the insertion of the tubes in patients who
      cannot be moved and in those patients with severe impairment of the peristaltic
      activity of the stomach.

PMID- 8874310
TI  - Dopaminergic receptor-mediated effects in the mesenteric vasculature and renal
      vasculature of the chronically instrumented newborn piglet.
AB  - OBJECTIVE: To determine the effects of stimulation of vascular dopaminergic
      receptor subtype 1 (dopamine-1) receptors in the renal and mesenteric vascular
      beds of a neonatal model. DESIGN: Prospective, unblinded, dose-response
      evaluation in an awake animal. SETTING: University research laboratory. SUBJECTS:
      Thirty newborn piglets, obtained and instrumented at 1 to 3 days of age and
      studied 48 hrs later. INTERVENTIONS: Animals were chronically instrumented with
      transit time ultrasound flow probes around the left renal and superior mesenteric
      arteries. They were then intravenously infused with either dopamine (2 to 32
      micrograms/kg/min) or fenoldopam (1 to 100 micrograms/kg/min), which is a
      selective agonist of the dopamine-1 receptor. MEASUREMENTS AND MAIN RESULTS:
      Blood pressure was only significantly increased by the highest infusion rate of
      dopamine (32 micrograms/kg/min), from a mean of 78 mm Hg at baseline to 87 mm Hg.
      Mesenteric and renal vascular resistances were unchanged by dopamine at any dose.
      Dopamine at 32 micrograms/kg/min decreased renal blood flow by 16.6 +/- 19.6 (SD)
      % and increased renal vascular resistance by 39.6 +/- 41.1% (p < .05). Mesenteric
      blood flow increased by 15% at 32 micrograms/kg/min (p < .05) but mesenteric
      vascular resistance was not affected by dopamine. Fenoldopam reduced blood
      pressure at infusion rates of 5, 10, and 100 micrograms/kg/min. Fenoldopam had no
      effect on renal vascular resistance at any dose. Fenoldopam reduced mesenteric
      vascular resistance at 5 micrograms/kg/min and at all higher doses. CONCLUSIONS:
      These data demonstrate the absence of dopaminergic receptor-mediated vasodilation
      in the porcine neonatal renal vascular bed. In the mesenteric artery, dopamine-1
      receptor-mediated vasodilation may be obtained. Dopamine itself, probably because
      of stimulation of other receptors, causes renal artery vasoconstriction and does
      not increase superior mesenteric artery blood flow.

PMID- 8874308
TI  - A randomized, blinded trial of high-dose epinephrine versus standard-dose
      epinephrine in a swine model of pediatric asphyxial cardiac arrest.
AB  - OBJECTIVE: To determine whether high-dose epinephrine administration during
      cardiopulmonary resuscitation (CPR) in a swine pediatric asphyxial cardiac arrest
      model improves outcome (i.e., resuscitation rate, survival rate, and neurologic
      function) compared with standard-dose epinephrine. DESIGN: A randomized, blinded
      study. SETTING: A large animal cardiovascular laboratory at a university.
      SUBJECTS: Thirty domestic piglets (3 to 4 months of age) were randomized to
      receive standard-dose epinephrine (0.02 mg/kg) or high-dose epinephrine (0.2
      mg/kg) during CPR after 10 mins of cardiac standstill with loss of aortic
      pulsation after endotracheal tube clamping. INTERVENTIONS: Two minutes of CPR
      were provided, followed by advanced pediatric life support. Successfully
      resuscitated animals were supported in an intensive care unit (ICU) setting for 2
      hrs and then observed for 24 hrs. MEASUREMENTS AND MAIN RESULTS:
      Electrocardiogram, thoracic aortic blood pressure, and right atrial blood
      pressure were monitored continuously until the intensive care period ended.
      Survival rate and neurologic outcome were determined. Return of spontaneous
      circulation was obtained in 13 of 15 high-dose epinephrine piglets vs. ten of 15
      standard-dose epinephrine piglets (p < .20). Four of 13 high-dose piglets died in
      the ICU period after initial resuscitation vs. 0 of ten standard-dose piglets (p
      < or = .05). Nine high-dose piglets survived 2 hrs vs. ten standard-dose piglets.
      Three piglets in each group survived for 24 hrs, but all were severely
      neurologically impaired. Two minutes after resuscitation, piglets treated with
      high-dose epinephrine had higher heart rates (210 +/- 24 vs. 189 +/- 40
      beats/min, p < .05) and higher aortic diastolic pressures (121 +/- 39 vs. 74 +/-
      40 mm Hg, p < .01). Within 10 mins of return of spontaneous circulation, severe
      tachycardia (> 240 beats/min) was more frequently noted in the high-dose group
      than in the standard-dose group (p < .05). All four high-dose piglets that died
      in the ICU period experienced ventricular fibrillation within 10 mins of return
      of spontaneous circulation. CONCLUSIONS: High-dose epinephrine did not improve 2
      hr survival rate, 24-hr survival rate, or neurologic outcome. High-dose
      epinephrine resulted in severe tachycardia and hypertension immediately after
      resuscitation and in a higher mortality rate immediately after resuscitation.

PMID- 8874311
TI  - Effect of tris buffer on free cytosolic calcium in myocardial cells.
AB  - OBJECTIVE: To study the effect of tris buffer on free cytosolic calcium in vitro.
      DESIGN: Open, randomized, control trial of dispersed rat myocardial cells.
      SETTING: Experimental laboratory in a large university hospital. SUBJECTS:
      Dispersed myocardial cells from Sprague-Dawley rats. INTERVENTIONS: The
      influences of pure trometamol (tris) and a tris butter mixture, as well as
      conventional sodium bicarbonate on free cytosolic calcium in suspended rat
      myocardial cells were studied with the fluorescent intracellular probe fura-2.
      MEASUREMENTS AND MAIN RESULTS: Addition of pure trometamol (tris) resulted in a
      significant increase of free cytosolic calcium in myocardial cells suspended in a
      buffer containing 1.25 mM of ionized calcium. The actions of trometamol display a
      dose-dependency in relation to the concentration of external ionized calcium
      since the ionized calcium response was reduced in a buffer with 0.5 mM of
      extracellular ionized calcium. Furthermore, removal of external ionized calcium
      totally prevented trometamol induced increases of ionized calcium, indicating
      that this increase is dependent on transmembrane ionized calcium fluxes. When
      tris buffer mixture was investigated in 1.25 mM of calcium, as well as 0.5 mM of
      external ionized calcium, a decrease of ionized calcium was noted initially,
      followed by an increase during the observation period. Addition of sodium
      bicarbonate to the two experimental settings resulted in a more prominent initial
      decrease of ionized calcium, followed by a slower increase which did not reach
      the initial values during the 20-min observation period. Extracellular pH was
      also included as a variable. When the cells were suspended in a buffer containing
      1.25 mM of ionized calcium with a pH of 6.80 instead of 7.40 (as above), addition
      of pure trometamol also resulted in an increase of ionized calcium; however,
      after 20 mins this increase was smaller as compared with the results above. When
      tris buffer mixture as well as sodium bicarbonate was added, initial decreases of
      ionized calcium were recorded, followed by smaller increases during the
      observation period, compared with the increase in buffers with a pH of 7.40.
      CONCLUSIONS: Pure trometamol (tris) induces an increase in free cytosolic calcium
      in suspended myocardial cells.

PMID- 8874314
TI  - Vertebrobasilar thrombosis: diagnosis, management, and the use of intra-arterial
      thrombolytics.
AB  - OBJECTIVES: To review the diagnosis and management of vertebrobasilar thrombosis
      and to discuss the use of thrombolytics in the treatment of this disease. DATA
      SOURCES: Selected references discussing epidemiology, anatomy, pathophysiology,
      diagnosis, therapy, and rehabilitation of vertebrobasilar occlusive disease.
      STUDY SELECTION: Studies addressing acute intervention and outcome in the therapy
      of vertebrobasilar thrombosis were reviewed. DATA EXTRACTION: Only those studies
      with angiographic documentation of arterial thrombosis and, in the case of
      thrombolysis, recanalization, were considered valid. DATA SYNTHESIS: Thrombosis
      of the vertebrobasilar system is a highly fatal disease and should be treated as
      a neurologic emergency. The key to effective management depends on early
      recognition of the symptom complex and a thorough understanding of the anatomy
      and pathophysiology of the disease process. CONCLUSIONS: A timely, integrated,
      multidisciplinary approach to the patient with vertebrobasilar thrombosis can
      improve outcome. The use of thrombolytics in the treatment of vertebrobasilar
      occlusion holds promise but the benefits have not yet been proven in a
      controlled, randomized study.

PMID- 8874312
TI  - Extramyocardial acidosis impairs cardiac resuscitability in isolated, perfused,
      rat hearts.
AB  - OBJECTIVES: Patients suffering out-of-hospital cardiac arrest have various
      degrees of acidemia when cardiopulmonary resuscitation is initiated. Myocardial
      hypercarbia, rather than decreases in myocardial pH, may determine cardiac
      resuscitability. Accordingly, we questioned whether different degrees of acidemia
      accompanying cardiac arrest affect cardiac resuscitability. We evaluated the
      effect of different degrees of extramyocardial acidosis on cardiac performance
      and resuscitability after ventricular fibrillation using isolated, perfused, rat
      hearts. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental
      animal laboratory in a university hospital. SUBJECTS: Thirty-one male, Sprague
      Dawley rats. INTERVENTIONS: Rat hearts were perfused with N-[2
      hydroxyethyl]piperazine-N-[2-ethanesulfonic acid] (HEPES) buffered solution
      (sodium chloride 145 mM, potassium chloride 4 mM, sodium dihydrogen phosphate
      dihydrate 1.25 mM, magnesium chloride 1.5 mM, calcium chloride 2 mM, HEPES 6 mM,
      glucose 10 mM), which was bubbled with 100% oxygen and adjusted to a pH of 7.4.
      The perfusion pressure was held constant at 60 mm Hg. After 60 mins of
      stabilization, the control perfusion solution was switched to one of the
      solutions titrated to pH 6.2, 6.5, 6.8, 7.1, or 7.4, using 1 N of sodium
      hydroxide. Hearts were allocated randomly to each group. After 15 mins of
      perfusion, the perfusion was discontinued, and artificial ventricular
      fibrillation was induced by electrical stimulation for 5 mins. The hearts were
      then perfused again in one of the same acidotic solutions for 30 mins.
      MEASUREMENTS AND MAIN RESULTS: Left ventricular developed pressure (left
      ventricular pressure minus end-diastolic left ventricular pressure), positive
      change in left ventricular pressure over time, heart rate (HR), and coronary flow
      were continuously measured. After 60 mins of stabilization, the values of left
      ventricular developed pressure, positive change in left ventricular pressure over
      time, HR, and coronary flow were not significantly different between groups.
      After 5 mins of ventricular fibrillation, all hearts were asystolic and left
      ventricular developed pressure, positive change in left ventricular pressure over
      time, HR, and coronary flow were all zero. After 30 mins of reperfusion, all
      values in the acidotic groups were significantly lower than the values in the pH
      7.4 group. When we judged the recovery of left ventricular developed pressure at
      > 35 mm Hg as "resuscitated," resuscitability was impaired at a pH of < 7.1. No
      hearts recovered after perfusion below a pH of 6.5. CONCLUSIONS: Extramyocardial
      acidosis below pH 7.1 decreased cardiac performance and resuscitability after
      ventricular fibrillation. This result indicates that progressive acidemia during
      cardiac arrest is one of the important determinants of cardiac resuscitability.

PMID- 8874313
TI  - Lisofylline decreases white cell adhesiveness and improves survival after
      experimental hemorrhagic shock.
AB  - OBJECTIVE: Lisofylline is an enantiomer-specific, alkyl-substituted
      methylxanthine, which has specific and potent activity in down-regulating
      leukocyte activation. This study was designed to test the efficacy of lisofylline
      in the resuscitation of rats subjected to experimental hemorrhagic shock. DESIGN:
      Prospective, randomized, and blinded survival studies were performed with two
      lisofylline dosing regimens added to fluid resuscitation in a shock model. In
      addition, white cell adhesiveness was measured to assess the effects of
      lisofylline. SETTING: Animal laboratory. SUBJECTS: Sixty Sprague-Dawley rats.
      INTERVENTIONS: Lisofylline or placebo was added to the resuscitation regimen,
      either as a single dose or over 24 hrs. MEASUREMENTS AND MAIN RESULTS: The 72-hr
      survival rate, white blood cell count, and platelet adhesiveness were determined.
      When a single 1-hr infusion of lisofylline was added to the initial resuscitation
      regimen, the 72-hr survival rate increased from 20% in controls to 50% (p <
      .009). When repeated doses of lisofylline were given over 24 hrs, the 72-hr
      survival rate increased from 40% in controls to 70% (p < .02). Control animals
      significantly increased leukocyte adhesiveness after shock and resuscitation.
      This increased adhesiveness was completely eliminated by lisofylline infusion.
      Platelet adhesiveness was not affected by lisofylline. CONCLUSIONS: Lisofylline
      improves survival in this model of hemorrhagic shock. Its beneficial effect may
      be related to down-regulation of leukocyte adhesiveness.

PMID- 8874315
TI  - Severe head injury in the United Kingdom and Ireland: a survey of practice and
      implications for management.
AB  - OBJECTIVE: To study the current intensive care management of patients with severe
      head injury (defined as a Glasgow Coma Scale score of < or = 8) in neurosurgical
      referral centers in the United Kingdom (UK) and ireland. DATA COLLECTION: A
      questionnaire was sent to the directors of the 44 neurosurgical referral units
      identified from the UK Medical Directory. After 4 wks, a copy of the
      questionnaire was sent to all nonresponders, with a cover letter urging them to
      respond. The aim was to collect data regarding the characteristics of the
      intensive care units (ICU), sedation, monitoring modalities used, the treatment
      of intracranial hypertension, and general care of severely head-injured patients.
      DATA EXTRACTION: Forty completed questionnaires were returned. Only 35 (88%)
      centers provided care for the severely head-injured as defined in the
      questionnaire. Patients were managed in specialized neurosurgical ICUs in 66% of
      centers and in general ICUs in the remainder of the centers. The ICUs were
      coordinated by an anesthesiologist in 66% of instances and by a neurosurgeon in
      23%. The mean number of beds per units was 7.9 (range 4 to 16), with 1:1
      nurse/bed ratio and 5.5 nurses per bed (total number of nursing staff per bed)
      (range 2.75 to 8). Annual caseload varied between units with the majority of
      units (49%) receiving between 25 and 50 patients with severe head injury, 23%
      receiving between 50 and 100 patients with severe head injury, and 29% receiving
      > 100 patients with severe head injury. There was considerable variability in
      both the nature of monitoring and therapy between centers. Although blood and
      central venous pressures were invasively monitored in > 50% of the patients in
      94% and 77% of the centers, respectively, intracranial pressure was only
      monitored routinely in 57% of the centers. Jugular venous bulb oximetry,
      transcranial Doppler ultrasonography, electroencephalography, and near-infrared
      spectroscopy were rarely used. Nearly all centers used propofol and midazolam for
      sedation, with morphine, fentanyl, and alfentanil as the main analgesics. Muscle
      relaxation was commonly used, with 40% of the centers employing it in 100% of
      their patients. Atracurium and vecuronium were the most commonly used agents.
      Only 68% of the centers had a protocol for the treatment of intracranial
      hypertension. Although hyperventilation to a Paco2 of 26 to 30 torr (3.5 to 4.0
      kPa) was the norm in the majority of centers (56%), two centers aimed for Paco2
      values < 26 torr (< 3.5 kPa). A quarter of the units did not aim for a cerebral
      perfusion pressure of > 60 mm Hg. Mild hypothermia was rarely used and 14% of the
      centers continued to use corticosteroids for the treatment of intracranial
      hypertension as a result of head trauma. CONCLUSION: We conclude that there are
      wide variations in the management of the severely head-injured patient in the UK
      and Ireland. Some of the therapies employed are not supported by available
      research findings. Rationalization (using rational management, i.e., based on
      good evidence) of the intensive care management of severe head injury with the
      development of widely accepted guidelines may result in an improvement in the
      quality of care of the head-injured patient.

PMID- 8874317
TI  - How to keep up with the critical care literature and avoid being buried alive.
AB  - OBJECTIVE: To provide practical suggestions for accessing, utilizing, and storing
      the rapidly expanding literature on critical care. DATA SOURCES: Original
      research on information sources for clinicians and techniques for keeping up with
      the literature, found through bibliographic searches, our personal files, and
      consultation with critical care colleagues. DATA SYNTHESIS: Suggestions for
      keeping up with the critical care literature include: 1) focus the clinical
      question; 2) locate literature using bibliographic databases; 3) use original
      journal articles; 4) use systematic reviews with confidence; 5) use text-books
      with caution; 6) read the preappraised literature; 7) abandon advertisements; 8)
      throw away the throwaways; 9) teach yourself critical appraisal; 10) be wary of
      overinterpretation of substitute end points; 11) teach yourself basic clinical
      statistics; 12) engage in effective browsing; 13) store useful articles; 14)
      invest in informatics; and 15) implement evidence-based practice guidelines.
      CONCLUSION: Efficient access, appraisal, and application of the literature on
      intensive care are basic skills for intensivists, who have adopted a variety of
      resourceful and pragmatic methods for "keeping up."

PMID- 8874316
TI  - Economic impact of prolonged motor weakness complicating neuromuscular blockade
      in the intensive care unit.
AB  - OBJECTIVE: We compared a case-series of ten patients who developed prolonged
      neuromuscular weakness after continuous, nondepolarizing, neuromuscular blockade
      with a group of controls without neuromuscular weakness to determine the economic
      impact of the neuromuscular weakness. DESIGN: Frequency-matched case control
      trial. SETTING: Medical and surgical intensive care units of a 937-bed tertiary
      care, university-affiliated teaching hospital. PATIENTS: Ten patients developed
      prolonged neuromuscular weakness after continuous administration of
      nondepolarizing neuromuscular blockers. Ten patients from a 1994 drug utilization
      database who did not develop motor weakness after paralysis were identified to
      serve as controls. MEASUREMENTS AND MAIN RESULTS: The medical and accounting
      records of the patients were retrospectively reviewed. Charge data were obtained
      from patient accounts. Institutional ratios to convert charges to full costs and
      marginal costs were obtained from the Hospital Finance Department of Henry Ford
      Hospital. The economic impact of the diagnosis and recovery of the motor weakness
      was estimated for the intensive care unit (ICU) and hospital stays and compared
      with those values for control patients. Median hospital charges (excluding
      rehabilitation), totaling $91,476, were attributed to the patients who developed
      neuromuscular weakness and included charges for neuromuscular blocking agents,
      continuous mechanical ventilation, ICU and hospital beds, neurologic studies, and
      physical therapy services. In the control patients, median charges were $22,191
      (p = .001). The total median cost differential for a patient in the neuromuscular
      weakness group was in excess of $66,713 (95% confidence interval $23,485 to
      $189,214, p = .001). Significant differences were also found for patient charges,
      full costs, and marginal costs for mechanical ventilation (p = .002), neurologic
      studies (p = .014), as well as ICU (p = .002) and hospital (p = .001) stays.
      CONCLUSIONS: The development of motor weakness was associated with an increase in
      ICU and hospital stays, continued mechanical ventilation, and disproportionate
      healthcare expenditures in excess of $66,000 per patient. A prospective
      evaluation of the true prevalence of neuromuscular weakness after neuromuscular
      blockade and of the costs to the healthcare system is needed.

PMID- 8874318
TI  - Quality of life measures.

PMID- 8874319
TI  - Selecting patients with cisplatin-resistant germ cell tumors for high-dose
      chemotherapy.

PMID- 8874320
TI  - Interferons as biochemical modulators.

PMID- 8874321
TI  - Treatment of germ cell cancer with two cycles of high-dose ifosfamide,
      carboplatin, and etoposide with autologous stem-cell support.
AB  - PURPOSE: To evaluate the activity of two cycles of high-dose ifosfamide,
      carboplatin, and etoposide (ICE) with autologous hematopoietic progenitor cell
      support (aHPCS) in patients with poor-prognosis, chemotherapeutically sensitive
      germ cell cancer. PATIENTS AND METHODS: Twenty patients with germ cell tumor who
      had persistent disease or relapse from standard-risk or high-risk presentation
      were entered on this pilot study. The entry criteria included relapsed gonadal
      and extragonadal germ cell cancer unlikely to be cured by standard salvage
      therapy but without proven refractoriness to chemotherapy. Treatment consisted of
      two cycles of ICE chemotherapy with mesna uroprotection and aHPCS. On the first
      cycle, ifosfamide (IFX), 2 gm/m2; carboplatin, 400 mg/m2; and etoposide, 20
      mg/kg, were administered on days -6, -5, and -4. On the second cycle, the doses
      and schedule of carboplatin and etoposide were identical, and patients with
      normal renal function received additional IFX, 2 g/m2 on day -3 and 1 g/ m2 on
      day -2. Mesna, 600 mg/m2 every 6 hours, was given until 24 hours following the
      final dose of IFX on each cycle, and autologous bone marrow and/or peripheral
      stem-cells were infused on day 0. RESULTS: All twenty patients are assessable for
      toxicity and current disease status. Two patients received only one cycle of
      therapy, one because of the development of active hepatitis C following cycle 1,
      and one because of renal insufficiency. No patient died as a result of protocol
      therapy, and no patient developed debilitating peripheral neuropathy, symptomatic
      hearing loss, or severe renal insufficiency requiring dialysis. The median time
      to recovery of > or = 500 neutrophils/microL and platelets > or = 50,000/microL
      was day +11 and day +15, respectively. The median maximum creatinine was 1.6
      mg/dL on each treatment cycle, and there was no other significant organ toxicity.
      With a median follow-up of 45 months, nine patients are alive and disease-free
      following protocol chemotherapy. One patient with embryonal cancer developed
      progressive pulmonary metastases 3 months after completing high-dose therapy,
      underwent complete resection of lung metastases, and remains disease-free at 63+
      months. Eight patients are continuously disease free at 23+ to 70+ months after
      protocol therapy. Eleven patients died of progressive disease between 4 and 23
      months following completion of treatment. CONCLUSION: These results compare
      favorably to other studies in similarly selected patients undergoing salvage
      therapy with one or two cycles of chemotherapy containing high-dose carboplatin
      and etoposide with or without cyclophosphamide (CTX) or IFX. The excellent safety
      and tolerability profile of this regimen and its encouraging activity in poor
      prognosis patients make it worthy of further study as part of initial therapy in
      randomized protocols for high-risk disease and early in the treatment of relapsed
      germ cell cancer.

PMID- 8874322
TI  - High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate
      analysis of prognostic variables.
AB  - PURPOSE: To identify prognostic variables for response and survival in male
      patients with relapsed or refractory germ cell tumors treated with high-dose
      chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND
      METHODS: Three hundred ten patients treated with HDCT at four centers in the
      United States and Europe were retrospectively evaluated. Univariate and
      multivariate analysis of patient, disease, and treatment characteristics were
      used for comparisons of response rates and failure-free survival (FFS). RESULTS:
      The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate
      analysis identified progressive disease before HDCT, mediastinal nonseminomatous
      primary tumor, refractory or absolute refractory disease to conventional-dose
      cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L
      before HDCT as independent adverse prognostic variables for FFS after HDCT. These
      variables were used to identify patients with good, intermediate, and poor
      prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%,
      compared with 27% and 5% in the intermediate-risk and poor-risk categories (P <
      .001). The increased risk for treatment failure was due to both a significantly
      lower rate of favorable responses and a significantly higher rate of relapses.
      Within the prognostic categories, the particular HDCT regimen or higher dosages
      of carboplatin or etoposide did not have a significant influence on treatment
      outcome. CONCLUSION: Prognostic variables for treatment response after HDCT can
      be identified. The proposed prognostic model might help to optimize the use of
      HDCT in germ cell tumors and warrants validation in future trials.

PMID- 8874323
TI  - Overexpression of p53 protein in a high-risk population of patients with
      superficial bladder cancer before and after bacillus Calmette-Guerin therapy:
      correlation to clinical outcome.
AB  - PURPOSE: We have previously demonstrated that p53 overexpression is predictive of
      disease progression and survival in Ta, Tis, and T1 tumors. Instillation of
      Bacillus Calmette-Guerin (BCG) is now accepted to be the most efficient adjuvant
      therapy for superficial bladder carcinoma. The aim of this study was to determine
      if p53 status, assessed before and after intravesical BCG therapy, can predict
      clinical outcome in a high-risk population of patients with superficial bladder
      carcinoma. MATERIALS AND METHODS: We examined 196 tissue specimens from 98
      patients, obtained immediately before and after intravesical BCG therapy. The
      pretherapy population was composed of 22 Ta, 57 Tis, and 19 T1 tumors. After BCG,
      66 specimens were TO and 32 had residual tumors. Nuclear p53 overexpression was
      analyzed in relation to time to disease progression and disease-specific
      survival. RESULTS: The median follow-up duration was 44 months. The detection of
      nuclear p53 overexpression before BCG therapy did not predict response to BCG
      therapy. Pre-BCG p53 protein overexpression, response to BCG therapy, and pre-BCG
      stage were all independent markers of disease progression. In patients with
      residual disease after BCG therapy (nonresponders), multivariate analysis
      confirmed that posttherapy p53 overexpression was the only independent marker of
      disease progression. CONCLUSION: In this high-risk population of patients with
      superficial bladder tumors, patients who have p53 nuclear overexpression in the
      tumor and stage T1 disease before BCG therapy are at high risk of disease
      progression. Furthermore, in the group of patients with residual disease after
      BCG therapy, p53 status is a better predictor of disease progression than post
      BCG stage.

PMID- 8874324
TI  - Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination
      with interferon-gamma and melphalan for nonresectable extremity soft tissue
      sarcomas: a multicenter trial.
AB  - PURPOSE: To determine the efficacy of isolated limb perfusion (ILP) with tumor
      necrosis factor-alpha (TNF) in combination with interferon-gamma (IFN) and
      melphalan as induction therapy to render tumors resectable and avoid amputation
      in patients with nonresectable extremity soft tissue sarcomas (STS). PATIENTS AND
      METHODS: Among 55 patients with 30 primary and 25 recurrent sarcomas, there were
      48 high-grade and seven grade 1 sarcomas (very large, recurrent, or multiple).
      The composition of this series of patients is unusual: 13 patients (24%) had
      multifocal primary sarcomas or multiple recurrent tumors; tumors were very large
      (median, 18 cm); and nine patients (16%) had known systemic metastases. IFN was
      administered subcutaneously on the 2 days before ILP with TNF, IFN, and
      melphalan. A delayed marginal resection of the tumor remnant was usually
      performed 2 to 3 months after ILP. RESULTS: A major tumor response was seen in
      87% of patients and rendered the sarcomas resectable in most cases. Clinical
      response rates were as follows: 10 (18%) completes responses (CRs), 35 (64%)
      partial responses (PRs), and 10 (18%) no change (NC). Final outcome was defined
      as follows by clinical and pathologic response: 20 (36%) CRs, 28 (51%) PRs, and
      seven (13%) NC. Limb salvage was achieved in 84% (follow-up duration, 20+ to 50+
      months). In 39 patients, resection of the tumor remnant (n = 31) or of two to
      eight tumors (n = 8) after ILP was performed; local recurrence developed in five
      (13%). When no resection was performed (multiple tumors or systemic metastases),
      local recurrences were frequent (five of 16), but limb salvage was often achieved
      as patients died of systemic disease. Regional toxicity was limited and systemic
      toxicity minimal to moderate with no toxic deaths. Histology showed hemorrhagic
      necrosis; angiographies showed selective destruction of tumor-associated vessels.
      CONCLUSION: ILP with TNF, IFN, and melphalan is a safe and highly effective
      induction biochemotherapy procedure that can achieve limb salvage in patients
      with nonresectable extremity STS. TNF is an active anticancer drug in humans in
      the setting of ILP.

PMID- 8874325
TI  - Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant
      treatment of high-risk resected cutaneous melanoma: an Eastern Cooperative
      Oncology Group study.
AB  - PURPOSE: To evaluate the quality-of-life effects of adjuvant high-dose interferon
      alfa-2b (IFN alpha 2b) treatment of high-risk melanoma. PATIENTS AND METHODS: A
      quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without
      Symptoms, and Toxicity [Q-TWiST]) was applied to the Eastern Cooperative Oncology
      Group Trial E1684, which compared high-dose IFN alpha 2b treatment for 1 year
      versus observation in 280 high-risk patients. IFN alpha 2b was administered at a
      dosage of 20 mU/m2 intravenously daily for 5 days per week for 4 weeks, and then
      three times weekly at 10 mU/m2 subcutaneously for 48 weeks. RESULTS: After 84
      months of median follow-up time, the IFN alpha 2b group gained a mean of 8.9
      months without disease relapse (P = .03) and 7.0 months of overall survival (P =
      .07) as compared with the observation group, but had severe treatment-related
      toxicity for 5.8 months, on average. The IFN alpha 2b group had more quality-of
      life-adjusted time than the observation group regardless of the relative
      valuations placed on time with toxicity (Tox) and time with relapse (Rel). This
      gain was significant (P < .05) for patients who consider Tox to have a high
      relative value and Rel to have a low relative value. In contrast, for patients
      who value Tox about the same as Rel, the quality-adjusted gain for IFN alpha 2b
      was not statistically significant. An analysis stratified according to tumor
      burden indicated that the benefit of IFN alpha 2b was greatest in the node
      positive strata. CONCLUSION: For patients with high-risk melanoma, the clinical
      benefits of high-dose IFN alpha 2b can offset the toxic effects. The optimal
      treatment for an individual patient depends on the patient's tumor burden and
      preferences regarding toxicity and disease relapse.

PMID- 8874326
TI  - Phase III randomized study to compare interferon alfa-2a in combination with
      fluorouracil versus fluorouracil alone in patients with advanced colorectal
      cancer.
AB  - PURPOSE: To compare the efficacy and toxicity profiles of a combination of
      fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IFN alpha 2a]
      Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5-FU alone in the
      treatment of advanced colorectal cancer (ACC). PATIENTS AND METHODS: A total of
      245 previously untreated ACC patients were randomized to receive either IFN alpha
      2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m2/d)
      by continuous intravenous (CIV) infusion on days 1 to 5 and then, after a 1-week
      hiatus, as a weekly IV bolus at the same dose (IFN/ 5-FU), or 5-FU alone at the
      same dose schedule (5-FU). RESULTS: There were no significant differences between
      IFN/5-FU and 5-FU alone in the overall response rate (24% v 17%, P = .2),
      duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3
      months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival
      duration (median, 13.9 v 13.2 months). Toxicity profiles were not statistically
      different except for constitutional symptoms, which were more frequent and more
      severe with IFN/5-FU. More patients interrupted treatment for adverse events
      (AEs) with IFN/ 5-FU (34%) than with 5-FU alone (21%) (P = .03). The number of
      deaths (mostly unrelated to drug treatment) during the study (8%) was similar
      with both regimens. CONCLUSION: The combination IFN/5-FU produced a response
      rate, response duration, and survival duration similar to that of 5-FU alone. The
      addition of IFN to 5-FU in the doses and schedules used in this study did not
      provide any further benefit over 5-FU alone and cannot be recommended for
      patients with metastatic ACC. This study confirms the value of large prospective
      randomized clinical trials to determine the clinical value of regimens that
      emerge from smaller single-center phase II studies.

PMID- 8874327
TI  - Fluorouracil and leucovorin with or without interferon alfa-2b in advanced
      colorectal cancer: analysis of a prospective randomized phase III trial. Hellenic
      Cooperative Oncology Group.
AB  - PURPOSE: To investigate if double modulation of fluorouracil (5-FU) with
      leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses
      and survival in comparison to single modulation of 5-FU with FA. PATIENTS AND
      METHODS: One hundred six patients with histologically confirmed advanced
      colorectal cancer, measurable disease, and without previous chemotherapy were
      prospectively randomized into two groups. Patients in group A received 5-FU 450
      mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a
      dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion.
      Patients in group B received exactly the same regimen plus IFN 2b 5 million units
      subcutaneously three times weekly. RESULTS: All patients were well balanced in
      both groups regarding age, sex, performance status, number, and site of
      metastasis. One hundred two patients were assessable. All patients have died.
      There was no difference in response between the two groups (7.8% v 9.8%). Median
      survival was 10.1 months in group A, and 7.2 months in group B (P = .00189).
      Median time to progression was 8.4 and 5.2 months, respectively (P = .00196).
      Overall, better performance status and older age had a positive impact on
      survival. Toxicity was the most important and catastrophic aspect of this study.
      Patients who received IFN 2b had significantly worse anemia, neutropenia,
      diarrhea, anorexia, weight loss, flu-like syndrome, and psychological reactions.
      CONCLUSION: Based on this final analysis, the addition of IFN 2b to the
      combination of 5-FU and FA enhances toxicity and contributes to decreased
      survival.

PMID- 8874328
TI  - Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical
      trial in colorectal cancer. Pharmacology and Molecular Mechanisms Group of the
      European Organization for Research and Treatment of Cancer.
AB  - PURPOSE: A pharmacokinetic study was performed during a phase II clinical trial
      of irinotecan (CPT-11) to confirm the pharmacokinetic profile of this drug and
      its metabolite and to investigate interpatient and intrapatient pharmacokinetic
      variations and pharmacokinetic-pharmacodynamic relationships. PATIENTS AND
      METHODS: Twenty-six men and 21 women (mean age, 61 years) with metastatic
      colorectal cancer, performance status less than 3 (World Health Organization
      [WHO] scale), and normal renal and hepatic function were administered CPT-11 (350
      mg/m2) by 30-minute intravenous (IV) infusion every 21 days. CPT-11 and its
      metabolites SN-38 and SN-38 glucuronide (SN-38G) were determined by high
      performance liquid chromatography (HPLC) using fluorimetric detection. RESULTS:
      The mean CPT-11 clearance and area under the concentration-time curve (AUC) were
      15.2 L/h. m2 and 24,769ng. h/mL, respectively. The large difference in SN-38 and
      SN-38G AUCs (559 v 2,283 ng. h/mL) was suggestive of extensive glucuronidation of
      SN-38. Interindividual variation in the metabolic ratio ([AUCSN-38 + AUCSN
      38Gl/AUCCPT-11) was marked (coefficient of variation [CV] = 51.6%] compared with
      intrapatient variation in this variable (CV = 32.6%). A significant relationship
      existed between percentage reduction in neutrophil count and the AUC of CPT-11 (r
      = .597, P < .001) and SN-38 (r = .559, P < .001). No relationship was identified
      between any pharmacokinetic parameter and delayed diarrhea or therapeutic
      outcome. CONCLUSION: Interindividual variations in the metabolic ratio suggest
      interpatient variation in carboxylesterase activity. Furthermore, glucuronidation
      of SN-38 may also be in part responsible for the large interpatient variability
      in the total SN-38 AUC. Conversely, low intrapatient variation of this parameter
      was observed in this study, which indicates a lack of autoinduction of the
      carboxylesterase system. The relationship between neutropenia and both CPT-11 and
      SN-38 pharmacokinetic parameters confirms the results of previous studies.

PMID- 8874329
TI  - p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of
      survival in patients with advanced hepatic metastases.
AB  - PURPOSE: To determine whether p53 protein expression is similar within primary
      colorectal cancer (CRC) and synchronous regional and distant metastases and to
      assess whether p53 nuclear protein expression could predict outcome in patients
      with synchronous unresectable liver metastases treated by hepatic artery
      infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from
      tumor and corresponding normal mucosa representative of 50 consecutive advanced
      CRC cases were examined for p53 nuclear protein expression by
      immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53
      nuclear expression were correlated with standard clinicopathologic variables and
      outcome, including response to HAI and survival. In a subset analysis, the
      pattern of nuclear p53 immunoreactivity was compared between primary CRC and
      lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for
      p53 protein was found in 72% of cases. The pattern of p53 protein expression in
      lymph node and liver metastases was identical to that of the primary tumor. The
      median survival time was 21.0 months in patients with p53-positive tumors and
      53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two
      year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant
      difference was found in the response rates to HAI chemotherapy between the two
      groups. By multivariate analysis, p53 protein status was the single best
      predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results
      indicate that nuclear p53 protein status in primary CRC is similar to that in
      metastatic sites and may be the dominant predictor of survival in patients with
      advanced hepatic metastases.

PMID- 8874330
TI  - c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early
      stage breast cancer without axillary lymph node metastases.
AB  - PURPOSE: We studied retrospectively the interaction between c-erbB2
      overexpression and adjuvant tomoxifen in node-negative breast cancer patients
      enrolled in the Gruppo Universitario Napoletano 1 (GUN-1) trial. PATIENTS AND
      METHODS: c-erbB2, evaluated by immunohistochemistry in 145 of 173 patients
      randomly assigned to 2-year adjuvant tamoxifen or no further therapy, was
      considered overexpressed if greater than 10% of the cells showed specific
      membrane staining. The role of each prognostic variable and their independent
      effect were studied using the Cox model. Disease-free (DFS) and overall (OAS)
      survival curves were estimated by the Kaplan-Meier method. RESULTS: As of
      November 30, 1994, the median follow-up period was 12 years. c-erbB2 was
      overexpressed in 43 of 145 patients (29.7%), which directly correlated with tumor
      size and inversely with estrogen receptor (ER) level. At univariate analysis,
      overexpression of c-erbB2 did not affect either DFS or OAS; tamoxifen had a
      greater effect on reducing the risk of recurrence than of death. Addition of c
      erbB2 to a multivariate Cox model that contained menopausal status, tumor size,
      nuclear grade, and treatment as covariates did not affect the significance of the
      model for DSF or OAS, whereas addition of the first-order interaction between c
      erbB2 and tamoxifen was statistically significant both for DFS and OAS. The same
      result was obtained when the model contained ER status and ER-tamoxifen
      interaction. Indeed, adjuvant tamoxifen significantly prolonged DFS and OAS in c
      erbB2-negative cases, whereas it had no effect on DFS and OAS in c-erbB2-positive
      patients. CONCLUSION: In early-stage breast cancer patients, overexpression of c
      erbB2 is a marker of lack of efficacy of adjuvant tamoxifen.

PMID- 8874331
TI  - Phase II study of the progesterone antagonist mifepristone in patients with
      untreated metastatic breast carcinoma: a National Cancer Institute of Canada
      Clinical Trials Group study.
AB  - PURPOSE: Mifepristone (RU486) is a progesterone receptor (PgR) antagonist that
      has been shown to be active in some preclinical hormone-dependent breast cancer
      tumor models and to produce a few responses in patients with pretreated
      metastatic disease in two small trials. This trial was designed to assess the
      response rate and toxic effects of mifepristone in a favorable group of women
      with PgR-positive recurrent breast cancer who had received no prior therapy.
      METHODS: Postmenopausal patients with PgR-positive, bidimensionally measurable
      disease were eligible provided they had received no other therapy for recurrence.
      Prior adjuvant hormonal treatment was permitted if a disease-free interval of at
      least 24 months had been observed. Mifepristone 200 mg was given daily and
      disease was reassessed every 4 weeks. Standard criteria for tumor response and
      toxic effects were used. RESULTS: A total of 28 patients were registered in the
      trial: all were eligible and assessable. Three partial responses were noted for
      an overall response rate of 10.7% (95% confidence interval [CI], 2% to 28%).
      Toxic effects were generally mild to moderate and consisted primarily of nausea,
      lethargy, anorexia, and hot flashes. CONCLUSION: Mifepristone had minimal
      activity in this optimal group of patients. While there may be reason to conduct
      some clinical studies with it in combination with antiestrogens on the basis of
      some preclinical work, our data do not support its use as a single agent in the
      management of breast cancer.

PMID- 8874332
TI  - Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a
      phase I study of paclitaxel and doxorubicin in patients with metastatic breast
      cancer.
AB  - PURPOSE: To determine whether a schedule-dependent interaction occurs when
      paclitaxel and doxorubicin are administered sequentially. PATIENTS AND METHODS:
      Ten patients with metastatic breast cancer received paclitaxel 125 mg/m2 over 24
      hours either immediately before or after doxorubicin 48 mg/m2 over 48 hours as
      the initial chemotherapy treatment. Two such courses were given, and the sequence
      of administration was reversed after course 1. In cohort 1, paclitaxel preceded
      doxorubicin for course 1. In cohort 2, doxorubicin preceded paclitaxel for course
      1. Doxorubicin levels were measured serially during the infusion and for 24 hours
      following it. Patients were assessed clinically for the occurrence of stomatitis
      and infection and granulocyte counts were measured twice weekly. RESULTS: Eight
      patients had complete pharmacokinetic sampling for both courses. The mean end-of
      infusion plasma doxorubicin concentrations (Cmax) were 70% higher in the
      paclitaxel-doxorubicin sequence compared with the reverse sequence (45 +/- 8
      ng/mL v 26 +/- 5 ng/ mL). The mean doxorubicin clearance was 32% lower in the
      paclitaxel-doxorubicin sequence (34.3 +/- 10.3 L/h v 51.6 +/- 16.1 L/h, P < .01).
      Clinically, hematologic and mucosal toxic effects were worse in the paclitaxel
      doxorubicin sequence. The median absolute granulocyte count was 0.2/microL in the
      paclitaxel-doxorubicin sequence and 1.3/microL in the doxorubicin-paclitaxel
      sequence. Seven of 10 patients who received the paclitaxel-doxorubicin sequence
      had grade 2 (n = 4) or 3 (n = 3) stomatitis, while only one of 10 patients who
      received the doxorubicin-paclitaxel sequence had grade 2 stomatitis and none had
      grade 3. CONCLUSION: When paclitaxel by 24-hour infusion precedes doxorubicin by
      48-hour infusion, doxorubicin clearance is reduced by nearly one third, which
      results in grade 2 and 3 stomatitis. To prevent this effect when paclitaxel (by
      24-hour infusion) and doxorubicin are administered sequentially, doxorubicin
      should be given first. The mechanisms for this effect are under investigation.

PMID- 8874333
TI  - Treatment-related leukemia in breast cancer patients treated with fluorouracil
      doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of
      Texas M.D. Anderson Cancer Center experience.
AB  - PURPOSE: Adjuvant chemotherapy for breast cancer has been the routine practice in
      the past decade. A number of studies have observed an increased incidence of
      treatment-related leukemias following chemotherapy with alkylating agents and/or
      topoisomerase II inhibitors. We evaluated the incidence of treatment-related
      leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant
      chemotherapy trials at The University of Texas M.D. Anderson Cancer Center.
      PATIENTS AND METHODS: Between 1974 and 1989, 1,474 patients with stage II or III
      breast cancer were treated in six prospective trials of adjuvant (n = 4) or
      neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and
      cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation
      time was 97 months. In 1,107 patients, FAC chemotherapy was given
      postoperatively; 367 patients received induction chemotherapy, as well as
      postoperative chemotherapy. Eight hundred ten patients had surgery followed by
      radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only.
      Patients in two adjuvant and one neoadjuvant study received higher cumulative
      doses of CTX compared with those in the other studies. RESULTS: Fourteen cases of
      leukemia were observed. Twelve of these patients had received radiotherapy and
      chemotherapy, and two had received chemotherapy only. Six of the reported
      patients with leukemia were treated with a cumulative CTX dose of greater than 6
      g/ m2. Five of these patients had received both radiotherapy and chemotherapy.
      The median latency period in the 14 patients was 66 months (range, 22 to 113).
      Six of 10 patients with adequate cytogenetic analyses had abnormalities that
      involved chromosomes 5 and/or 7. The rest of the patients had nonspecific
      cytogenetic abnormalities or lacked cytogenetic information. The 10-year
      estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for
      all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus
      chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only
      group; this difference was statistically significant (P = .01). The 10-year
      estimated leukemia risk for the higher-dose (> 6 g/m2) CTX group was 2% (95% CI,
      0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group,
      a difference that was not statistically significant (P = .53). CONCLUSION: These
      data illustrate that patients treated with adjuvant FAC chemotherapy plus
      radiotherapy have a slightly increased risk of leukemia. This information needs
      to be considered in the treatment plans for patients with breast cancer. However,
      for most patients, the benefits of adjuvant therapy exceed the risk of treatment
      related leukemia.

PMID- 8874334
TI  - Increased thromboembolic complications with concurrent tamoxifen and chemotherapy
      in a randomized trial of adjuvant therapy for women with breast cancer. National
      Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group.
AB  - PURPOSE AND METHODS: Associations between thromboembolism and malignancy, usually
      widespread, and between thromboembolism and hormonal and/or chemotherapy have
      been previously reported. We performed a randomized trial of tamoxifen 30 mg/d
      for 2 years (T) versus T plus 6 months of intravenous chemotherapy with
      cyclophosphamide, methotrexate, and fluorouracil (CMF) for postmenopausal women
      with involved axillary nodes and positive estrogen receptor (ER) or progesterone
      receptor (PgR) status following primary therapy for breast cancer. RESULTS: We
      observed one or more thromboembolic events in 48 of 353 women (13.6%) allocated
      to receive T plus CMF in comparison to five of 352 women (2.6%) randomized to
      receive T alone (P < .0001). Six women in the T plus CMF arm, but none randomized
      to receive T alone, suffered two thromboembolic events while an study therapy.
      There were also significantly more women who developed severe (grade 3 to 5)
      thromboembolic events in the T plus CMF arm than in the T arm (34 v five; P <
      .0001). Most thromboembolic events (39 of 54) occurred while women were actually
      receiving chemotherapy (P < .0001). Thromboembolic complications resulted in more
      days in hospital and more deaths than any other complication of therapy,
      including infection, in this trial. CONCLUSION: Thromboembolism related to the
      addition of CMF chemotherapy to tamoxifen as adjuvant therapy in this group of
      women represents a relatively common and serious complication that may outweigh
      any benefits offered by this additional therapy.

PMID- 8874335
TI  - Annual hazard rates of recurrence for breast cancer after primary therapy.
AB  - PURPOSE: To determine if the long-term increase of recurrence for breast cancer
      is stable or slowly decreasing, or if it ever reaches zero; and to determine the
      effect of prognostic factors on the hazard of recurrence. METHODS: All patients
      entered onto the seven completed and unblinded Eastern Cooperative Oncology Group
      (ECOG) coordinated studies of postoperative adjuvant therapy for breast cancer
      were analyzed in terms of annual hazard of recurrence of breast cancer. RESULTS:
      For the entire group, the peak hazard of recurrence occurred in the interval of 1
      to 2 years. The hazard decreased consistently in the interval of 2 to 5 years.
      Beyond 5 years, the hazard of recurrence decreased very, very slowly through year
      12. The average hazard of recurrence between years 5 and 12 for the entire
      population was 4.3% per year. The pattern of a peak hazard of recurrence during
      the first 5 years with a slowly decreasing hazard of recurrence beyond 5 years
      was also observed to varying degrees in most subsets. Higher risk subsets such as
      patients with more than three nodes positive had a higher hazard of recurrence at
      all time intervals, while lower risk subsets such as patients with negative nodes
      had a lower hazard of recurrence in all time periods. CONCLUSION: Patients 5
      years postsurgery for breast cancer appear to have a very slowly decreasing
      hazard of recurrence. The mean hazard of recurrence between years 5 to 12
      postsurgery is 4.3% per year. This group of patients may be well suited for
      trials evaluating cytostatic drugs or differentiating agents.

PMID- 8874336
TI  - Randomized trial of a psychologic distress screening program after breast cancer:
      effects on quality of life.
AB  - PURPOSE: Although psychosocial intervention can reduce psychosocial distress
      following breast cancer, many women who are experiencing problems are not
      identified and offered additional help. This trial assessed effects on quality of
      life of psychologic distress screening among newly diagnosed, nonmetastatic
      breast cancer patients. PATIENTS AND METHODS: From 1990 to 1992, all eligible
      patients in one regional breast cancer center were identified and offered study
      participation. Women in both control and experimental groups received brief
      psychosocial intervention from a social worker at initial treatment. The
      experimental group also had monthly telephone screening of distress levels using
      a brief, validated instrument, with additional psychosocial intervention offered
      only to those with high distress at screening. RESULTS: Among 282 eligible
      patients, 89% were randomized and completed the study. Participants' psychologic
      distress levels decreased over the study period (P = .0001). However, no between
      group differences were observed. Mean distress scores among control and
      experimental women at 0-, 3-, and 12-month interviews were 20.7 and 20.4, 15.5
      and 15.0, and 14.6 and 13.5, respectively. No between-group differences were
      observed with respect to physical health, functional status, social and leisure
      activities, return to work, or marital satisfaction. CONCLUSION: Our results
      indicate that, among patients who receive a minimal psychosocial intervention as
      part of their initial cancer care, a distress screening program does not improve
      quality of life. Minimal psychosocial intervention at initial treatment may be
      effective in reducing distress, thus making it difficult to obtain additional
      benefit from a screening program.

PMID- 8874337
TI  - The European Organization for Research and Treatment of Cancer breast cancer
      specific quality-of-life questionnaire module: first results from a three-country
      field study.
AB  - PURPOSE: To construct a breast cancer-specific quality-of-life questionnaire
      (QLQ) module to be used in conjunction with the European Organization for
      Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and
      validity cross-culturally. PATIENTS AND METHODS: Module construction took place
      after the EORTC guidelines for module development. The module--the QLQ-BR23-
      consists of 23 items covering symptoms and side effects related to different
      treatment modalities, body image, sexuality, and future perspective. This module
      was tested in 170 Dutch, 168 Spanish, and 158 American cancer patients at two
      points in time. The timing for the Dutch and Spanish patients was before and
      during treatment with radiotherapy or chemotherapy. For the American patients,
      the questionnaire was administered at admission at the breast clinic and 3 months
      after the first assessment. RESULTS: Multitrait scaling analysis confirmed the
      hypothesized structure of four of the five scales. Cronbach's alpha coefficients
      were, in general, lowest in Spain (range; .46 to .94) and highest in the United
      States (range; .70 to .91). On the basis of known-groups comparisons, selective
      scales distinguished clearly between patients differing in disease stage,
      previous surgery, performance status, and treatment modality, according to
      expectation. Additionally, selective scales detected change over time as a
      function of changes in performance status and treatment-induced change.
      CONCLUSION: These results lend support to the clinical and cross-cultural
      validity of the QLQ-BR23 as a supplementary questionnaire for assessing specific
      quality-of-life issues relevant to patients with breast cancer.

PMID- 8874339
TI  - Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in
      patients with stage IV non-small-cell lung cancer.
AB  - PURPOSE: This prospective randomized trial was performed to compare the
      effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil
      and leucovorin (5-FU/LV) on the primary end points of survival, quality of life
      (QOL), and relief of cancer-related symptoms in patients with advanced non-small
      cell lung cancer (NSCLC). Secondary end points included tumor response rates and
      time to treatment failure. In addition, the safety of both treatment regimens was
      evaluated in this multicenter study. PATIENTS AND METHODS: Two hundred sixteen
      patients with stage IV NSCLC were enrolled onto this study from 18 centers.
      Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered
      at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4
      weeks. Patients with progressive disease or toxicity were removed from study
      while responding and stable patients were continued on therapy. RESULTS: The
      median survival time of patients who received vinorelbine was 30 weeks, with 25%
      of patients alive at 1 year, compared with a median survival time of 22 weeks and
      16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank
      test). This improvement in survival was associated with a higher objective
      response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for
      vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was
      granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia.
      Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most
      common grade 3 toxicities were related to injection-site reactions. CONCLUSION:
      This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC.
      The clinical activity and relatively favorable toxicity profile of this agent
      make it a reasonable and useful treatment option in the management of patients
      with this disease.

PMID- 8874338
TI  - Combination but not single-agent methotrexate chemotherapy for gestational
      trophoblastic tumors increases the incidence of second tumors.
AB  - PURPOSE: No increase in second tumor incidence was found in a previous analysis
      of women treated with chemotherapy for gestational trophoblastic tumors (GTT).
      More patient years at risk enabled a further analysis of the risk of second
      tumors to be performed in the 1,377 women treated in this until up to 1990.
      PATIENTS AND METHODS: Health questionnaires were returned on 93.3% of patients
      who successfully completed chemotherapy and were living in the United Kingdom.
      The remainder were flagged for death or developing further cancers by the Office
      of Population Census and Surveys and by the Thames Cancer Registry. Incidence
      density analysis was performed based on 15,279 person-years of observation
      available. Standardized incidence ratio (SIR) was used to estimate the relative
      risk (RR) of second tumors associated with the treatment. To calculate the
      expected number, the actual incidence rates observed by the Thames Cancer
      Registry during the same calendar period of observation were used. RESULTS: An
      overall 50% excess of risk (RR = 1.5; 95% confidence interval [CI], 1.1 to 2.1; P
      < .011) was observed: there were 37 second tumors, when 24.5 were expected. For
      specific second tumors, the risk was significantly increased for myeloid leukemia
      (RR = 16.6; 95% CI, 5.4 to 38.9), colon (RR = 4.6; 95% CI, 1.5 to 10.7), and
      breast cancer when the survival exceeded 25 years (RR = 5.8; 95% CI, 1.2 to
      16.9). The risk was not significantly increased among the 554 women receiving
      single-agent therapy (RR = 1.3; 95% CI, 0.6 to 2.1). Leukemias only developed in
      patients receiving etoposide plus other cytotoxic drugs. CONCLUSION: This study
      suggests that there is a slight increased risk of second tumors after sequential
      or combination chemotherapy for GTT. This has become apparent since the
      introduction of etoposide and longer follow-up.

PMID- 8874340
TI  - Treatment of patients with small-cell lung cancer refractory to etoposide and
      cisplatin with the topoisomerase I poison topotecan.
AB  - PURPOSE: This study was designed to assess the anti-tumor activity of topotecan
      (TPT) in patients with small-cell lung cancer (SCLC) refractory to etoposide.
      PATIENTS AND METHODS: Refractoriness to etoposide was defined as lack of response
      to etoposide-containing frontline therapy, or progression during or within 3
      months of the last dose of etoposide-containing frontline or second-line therapy.
      Other eligibility criteria were presence of measurable disease, Zubrod scale
      performance status (PS) < or = 2, < or = two prior chemotherapy regimens, and
      adequate renal and liver function. TPT was administered at a dose of 1.25 mg/m2/d
      for 5 days over 30 minutes every 21 days. RESULTS: Thirty-two patients were
      registered, of whom 28 are fully assessable. All patients had been treated with
      frontline etoposide and cisplatin. Three patients (11%) achieved a partial
      remission (PR) (durations, 7, 8, and 19 weeks) and two (7%) achieved a minor
      response; five patients (17%) had stable disease and 18 (65%) had progressive
      disease. One of the three patients who achieved a PR had failed to respond to
      frontline cisplatin and etoposide. The overall median survival duration was 20
      weeks. Grade 3 to 4 granulocytopenia and thrombocytopenia occurred after 70% and
      31% of courses administered, respectively. No grade 3 to 4 non-hematological
      toxicities were observed. Grade 1 or 2 nonhematological toxicities (in percentage
      of patients) consisted of nausea (41%, 8%) and vomiting (25%, 11%), and alopecia
      (100%). CONCLUSION: TPT at the dose and schedule used has modest antitumor
      activity in SCLC patients refractory to etoposide and cisplatin, which indicates
      that clinical resistance to the topoisomerase II poison etoposide does not confer
      cross-sensitivity to the topoisomerase I poison TPT. TPT is well tolerated, with
      myelosuppression of short duration being the most common and limiting toxicity.

PMID- 8874341
TI  - In vivo purging of bone marrow in children with poor-risk neuroblastoma for
      marrow collection and autologous bone marrow transplantation.
AB  - PURPOSE: To evaluate the following prospectively in poor-risk neuroblastoma (NBL)
      patients: (1) the feasibility and efficacy of in vivo purging of bone marrow; and
      (2) the outcome after autologous bone marrow transplantation (ABMT) when
      immunologically tumor-free, unpurged autografts were used. PATIENTS AND METHODS:
      Twenty-three children with poor-risk NBL were evaluated during induction
      chemotherapy by repeat bone marrow examinations, including aspirate, biopsy, and
      an immunofluorescence method using the anti-GD2 monoclonal antibody 3A7. Nineteen
      patients completed the program with surgery with or without local irradiation
      followed by ABMT. RESULTS: Autologous bone marrow grafts, both immunologically
      and cytologically clean, were obtained and used in 19 of 23 children. The overall
      4-year disease-free survival of the 19 grafted children was 53%, with a toxic
      death rate of 16% and a posttransplant relapse rate of 37%. According to the in
      vivo purging efficacy of the 18 children with initial marrow disease, the
      following three groups were formed: patients with (1) perfect in vivo purging (n
      = 5); (2) eventually successful in vivo purging (n = 8); and (3) unsuccesful in
      vivo purging (n = 5). The 4-year DFS was 100%, 67%, and 0%, respectively (P <
      0.001). The five patients with unsuccessful in vivo purging failed because of
      resistant/progressive bulky disease. CONCLUSION: In patients with poor-risk NBL,
      in vivo purging of bone marrow by conventional chemotherapy is feasible, can be
      monitored, and the purging efficacy during the first 3 months after diagnosis is
      a strong prognostic factor reflecting tumor responsiveness to therapy.
      Autografting with immunologically clean, unpurged marrows gives a DFS well
      comparable to previous studies using ex vivo purging.

PMID- 8874343
TI  - Peripheral blast counts at diagnosis of late isolated bone marrow relapse of
      childhood acute lymphoblastic leukemia predict response to salvage chemotherapy
      and outcome. Berlin-Frankfurt-Munster Relapse Study Group.
AB  - PURPOSE: In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high
      tumor burden indicates a poor prognosis, while no such link has been established
      yet after relapse. The impact of the absolute peripheral blast count (PBC) at the
      time of relapse on the response to salvage chemotherapy after a late isolated
      bone marrow (BM) relapse is the subject of this prospective analysis. PATIENTS
      AND METHODS: Since 1983, 260 children with a first isolated BM relapse of ALL
      that occurred 6 months or later after elective cessation of front-line therapy
      were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt
      Munster (BFM) Relapse Study Group. All patients received intensive multiagent
      induction and consolidation chemotherapy for 6 months, followed by maintenance
      therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of
      subclinical meningeal leukemia consisted of high-dose intravenous MTX and
      intrathecally administered cytostatic drugs, which was augmented by cranial
      irradiation since 1988. RESULTS: At the time relapse was diagnosed, PBC varied
      considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL).
      Achievement of a second complete remission (CR) was not significantly different
      in children without detectable circulating blasts at relapse (37 of 38) and those
      with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51
      children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015).
      At a median follow-up time of 40 months, the 10-year event-free survival (EFS)
      probability was significantly (P = .0001) higher in children without circulating
      blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There
      was a preponderance of boys in the group without detectable circulating blasts,
      while the three PBC-defined groups did not differ with respect to frontline
      treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage
      treatment protocol. On sequential univariate and multivariate analysis, only
      duration of first remission > or = 48 months was an additional independent
      indicator of adverse prognosis, while preventive cranial irradiation improved
      outcome independently of PBC. CONCLUSION: The absence of blasts on peripheral
      blood smears at the time of a first late isolated BM relapse of childhood ALL is
      associated with a favorable response and prognosis in chemotherapy-treated
      children, who should be regarded as ineligible for bone marrow transplantation
      (BMT) unless a second round of chemotherapy has failed to produce a response.

PMID- 8874342
TI  - Intensive oral methotrexate protects against lymphoid marrow relapse in childhood
      B-precursor acute lymphoblastic leukemia.
AB  - PURPOSE: To describe the use of combination chemotherapy, including divided-dose
      oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic
      leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis.
      PATIENTS AND METHODS: Two hundred forty-three patients were treated from January
      1986 to May 1992. dMTX was given weekly during consolidation and biweekly for the
      first 16 months of continuation therapy with mercaptopurine (6-MP) and
      asparaginase (L-ASP). Initially, etoposide (VP-16) and cytarabine (Ara-C) pulses
      were included. Treatment continued for 30 months with single-dose weekly MTX
      replacing dMTX during continuation, part 2. Unexpected acute neurotoxicity was
      eliminated by the addition of leucovorin. VP-16 and Ara-C were omitted in the
      face of acute myelogenous leukemia (AML). RESULTS: Two hundred thirty-nine
      patients entered remission: 16 had a lymphoid marrow relapse, two each with
      testicular or CNS relapse; 19 a CNS relapse; 16 secondary AML; three other second
      malignancies; two withdrew for transplant; three died in remission; 16 withdrew
      because of noncompliance, and nine withdrew with toxicity. Event-free survival
      (EFS) at 4 years was 73 +/- 4%; 81 +/- 4% for 150 patients with better risk
      features and 60 +/- 7% for 93 with high-risk features. Lymphoid marrow relapse
      free survival in the standard- and high-risk patients was 94 +/- 3% and 86% +/-
      6%, respectively. The most common adverse event was secondary AML in the standard
      risk group and isolated CNS relapse in the high-risk group. CONCLUSION: This
      therapy produced an overall EFS similar to other published regimens, but the
      pattern of failures is very different, with few patients having a lymphoid marrow
      relapse. These data suggest that highly effective therapy for children with ALL
      can be delivered on an outpatient basis using a regimen featuring repetitive
      dMTX.

PMID- 8874344
TI  - Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary
      sarcomas.
AB  - BACKGROUND: An excess risk of second malignancies has been reported in survivors
      of Ewing's sarcoma. We examined a multiinstitutional data base to reevaluate the
      risk among survivors of Ewing's sarcoma and to identify possible causal factors.
      METHODS: Information was derived from a data base that included 266 survivors of
      Ewing's sarcoma. Cumulative incidence rates of second malignancies were
      calculated. Contributions of clinical features, type and dose of chemotherapy,
      and cumulative radiation dose to the risk of second malignancies were evaluated.
      RESULTS: After a median follow-up duration of 9.5 years (range, 3.0 to 30), 16
      patients have developed second malignancies, which included 10 sarcomas (five
      osteosarcomas, three fibrosarcomas, and two malignant fibrous histiocytomas) and
      six other malignancies (acute myeloblastic leukemia, acute lymphoblastic
      leukemia, meningioma, bronchioalveolar carcinoma, basal cell carcinoma, and
      carcinoma-in-situ of the cervix). The median latency to the diagnosis of the
      second malignancy was 7.6 years (range, 3.5 to 25.7). The estimated cumulative
      incidence rates at 20 years for any second malignancy and for secondary sarcoma
      were 9.2% (SD = 2.7%) and 6.5% (SD = 2.4%), respectively. The cumulative
      incidence rate of secondary sarcoma was radiation dose-dependent (P = .002). No
      secondary sarcomas developed among patients who had received less than 48 Gy,
      while the absolute risk of secondary sarcoma was 130 cases per 10,000 person
      years of observation among patients who had received > or = 60 Gy. CONCLUSION:
      The overall risk of second malignancies after Ewing's sarcomas is similar to that
      associated with treatment for other childhood cancers. The radiation dose
      dependency of secondary sarcomas justifies modification in therapy to reduce
      radiation doses.

PMID- 8874345
TI  - Neuropsychologic effects of chemotherapy on children with cancer: a longitudinal
      study.
AB  - PURPOSE: A prospective study was conducted to assess the effects of chemotherapy
      for cancer on children's long-term neuropsychologic status. PATIENTS AND METHODS:
      Ninety-nine children who received no cranial radiation therapy (CRT) completed
      four annual neuropsychologic assessments. Fifty-one patients received intrathecal
      (IT) chemotherapy (ITC); 48 received no CNS treatment. These two groups were
      compared using repeated-measures analysis of variance on IQ, memory, language,
      freedom from distractibility, academic achievement, executive functions, and fine
      motor, perceptual-motor, and tactile-spatial skills. In addition, 51 of the
      sample of 99 patients had been examined 5 to 11 years after diagnosis. Their data
      were analyzed to evaluate the longer-term effects of chemotherapy. The
      predictability of demographic and medical variables on neuropsychologic outcome
      at 3-year and long-term follow-up study were assessed using multiple regression
      techniques. RESULTS: Overall, the effects of chemotherapy in the absence of CRT
      appear to be slight. Patients who received ITC and intravenous (IV) methotrexate
      declined slightly on perceptual-motor skills, but were still well within the
      normal range. Both groups, regardless of treatment, declined on academic
      achievement tests, although not to a statistically significant degree. Age
      effects were found on performance IQ (PIQ) and perceptual-motor skills.
      Socioeconomic status (SES) correlated with a large number of variables. Sex
      effects were not significant. CONCLUSION: The present results are largely
      consistent with previous findings for nonirradiated groups. Treatment effects
      from ITC are slightly more apparent 5 to 11 years after diagnosis than at 3-year
      follow-up evaluation but this does not constitute a clinically meaningful
      difference. More noticeable are academic declines among all groups, regardless of
      treatment.

PMID- 8874346
TI  - Clinical experience with oral methadone administration in the treatment of pain
      in 196 advanced cancer patients.
AB  - PURPOSE: The aims of this study were to describe the analgesia, side effects, and
      dosage and the causes of suspension of treatment in a large sample of advanced
      cancer patients with pain after treatment with oral methadone from 7 to 90 days.
      PATIENTS AND METHODS: In a retrospective study, data collected for 196 advanced
      cancer outpatients with moderate to severe pain treated at 8-hour intervals with
      oral methadone in solution form from February 1993 to February 1995 were analyzed
      at baseline (time 0) and then at 7, 15, 30, 45, 60, and 90 days. The following
      parameters were assessed: Karnofsky Performance Status, intensity of pain (using
      the Integrated Pain Score [IPS], intensity of pain, insomnia, drowsiness,
      confusion, dry mouth, nausea, vomiting, constipation, and dyspnea (using the
      Therapy Impact Questionnaire [TIQ], mean daily dose of drug administered, and
      reasons for withdrawal from study. The period when pain was reduced by > or = 35%
      with respect to baseline was evaluated with the Palliation Index. The association
      of the degree of palliation of pain with the age of the patients, tumor site,
      analgesic treatment taken at baseline, and daily mean dose of methadone
      administered during the follow-up period was analyzed by means of the Kruskal
      Wallis test. RESULTS: A reduction in pain intensity with respect to baseline
      occurred at each analysis time, and in 55.1% of the patients the reduction during
      the follow-up period was > or = 35% according to the Palliation Index. The mean
      dose of oral methadone ranged from 14 mg at day 7 to 23.65 mg at day 90. There
      was an overall worsening of the other symptoms, but a high percentage of the
      patients reported an amelioration of insomnia with respect to baseline. There was
      a statistically significant association (P < .0001) between the Palliation Index
      and the analgesic therapy administered at baseline. Only 11.2% of the patients
      withdrew from the study due to analgesic inefficacy and 6.6% due to methadone
      related side effects (10 patients with drowsiness and three with severe
      constipation. CONCLUSION: Oral methadone administered every 8 hours was shown to
      be an appropriate analgesic therapy in the treatment of advanced cancer-related
      pain. The worsening of the other symptoms under study can be considered linked to
      the progression of the disease, and in fact, only a small percentage of the
      patients reported methadone-related side effects that warranted suspension of
      treatment. We consider oral methadone to be a useful analgesic therapy, and it
      should be considered in clinical practice for the treatment of cancer pain.

PMID- 8874348
TI  - The future of cancer research and the role of the National Cancer Institute.

PMID- 8874347
TI  - Clinical practice guidelines for the use of tumor markers in breast and
      colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical
      Oncology.
AB  - PURPOSE: The primary objective was to determine clinical practice guidelines for
      the use of tumor marker tests in the prevention, screening, treatment, and
      surveillance of breast and colorectal cancers. These guidelines are intended for
      use in the care of patients outside of clinical trials. METHODS: Six tumor
      markers for colorectal cancer and seven for breast cancer were considered. They
      could be recommended or not for routine use or for special circumstances. In
      general, the significant health outcomes identified for use in making clinical
      practice guidelines (overall survival, disease-free survival, quality of life,
      lesser toxicity, and cost-effectiveness) were used when data were available.
      Expert consensus was used to inform the recommendations for use of tumor markers
      when published evidence was insufficient. A computerized literature search was
      performed using Medline. In addition to reports collected by individual panel
      members, all articles published in the English-speaking literature from January
      1989 to April 1994 were collected for review and distributed to all members of
      the Panel. Values for use, utility, and levels of evidence were assigned by the
      expert reviewers and approved by the Panel. Tumor markers were assigned benefit
      if they had prognostic or predictive value that would lead to the favorable
      outcomes listed above. Harms considered were inappropriate disease management,
      and excess cost without definable benefit. Costs were considered but were never
      the sole determinant of a recommendation. RESULTS AND CONCLUSION: For colorectal
      cancer, it is recommended that carcinoembryonic antigen (CEA) levels be measured
      preoperatively if it would change surgical management. It is recommended that CEA
      levels be monitored every 2 to 3 months for > or = 2 years, if resection of liver
      metastasis would be clinically indicated. The data are insufficient to recommend
      the routine use of lipid-associated sialic acid (LASA), CA 19-9, DNA index, DNA
      flow cytometric proliferation analysis, p53 tumor suppressor gene, and ras
      oncogene. For breast cancer, estrogen receptor and progesterone receptor are
      recommended to be measured on every primary specimen, but on subsequent specimens
      only if it would lead to a change in management. The data are insufficient to
      recommend the routine use of DNA index, DNA flow cytometric proliferation
      analysis, CA 15-3, CEA, c-erbB-2, p53 or cathepsin-D. In the absence of readily
      measurable disease, CA 15-3 and CEA levels can be used to document treatment
      failure. New markers and new evidence will be evaluated by annual update of these
      guidelines.

PMID- 8874349
TI  - Dexrazoxane for protection against cardiotoxic effects of anthracyclines.

PMID- 8874350
TI  - Optimal management of residual mass after chemotherapy in advanced seminoma:
      there is time for everything.

PMID- 8874351
TI  - Perioperative chemotherapy versus adjuvant hormonal therapy in breast cancer:
      claimed benefits.

PMID- 8874352
TI  - Response to commentary on endometrial cancer deaths in tamoxifen-treated breast
      cancer patients.

PMID- 8874354
TI  - Funerals.

PMID- 8874353
TI  - Optimal duration of fluorouracil plus levamisole colon cancer surgical adjuvant
      therapy.

PMID- 8874355
TI  - Immunization services in rural areas.

PMID- 8874356
TI  - Ethics in managed care setting.

PMID- 8874357
TI  - Onychomycosis.

PMID- 8874358
TI  - Appropriateness of antibiotics.

PMID- 8874359
TI  - State medical boards' position on chaperones.

PMID- 8874361
TI  - Spinal manipulation.

PMID- 8874360
TI  - Spinal manipulation.

PMID- 8874362
TI  - Treating acute asthma in adults.

PMID- 8874363
TI  - Oral contraceptives and breast cancer.

PMID- 8874364
TI  - Safety of first trimester exposure to H2 blockers.

PMID- 8874365
TI  - Stroke in users of low-dose oral contraceptives.

PMID- 8874366
TI  - Glucose-based oral rehydration therapy.

PMID- 8874367
TI  - SSRI or tricyclics for depression?

PMID- 8874368
TI  - A cure for the common cold?

PMID- 8874369
TI  - Temporomandibular disorders in the medical practice.
AB  - Patients suffering with various orofacial pain conditions are likely to seek
      advice and treatment from a family physician. Temporomandibular disorders (TMD)
      are common in the general population, and the clinician should be aware of the
      common associated signs and symptoms so that proper therapy can be provided. The
      family physician can often provide initial therapies that are effective in
      reducing TMD symptoms. In some instances, it is appropriate for the family
      physician to refer the patient to a dentist for a more comprehensive evaluation
      of the masticatory system. This article describes the common patient complaints
      associated with TM disorders. A few simple therapies are discussed along with
      suggestions regarding the appropriate time for referral to a dentist for a
      thorough dental evaluation.

PMID- 8874370
TI  - One size doesn't fit all. Multimethod research yields new insights into
      interventions to increase prevention in family practice.

PMID- 8874371
TI  - An ounce of prevention? Evaluation of the 'Put Prevention into Practice' program.
AB  - BACKGROUND: The "Put Prevention into Practice" (PPIP) program was designed to
      enhance the capacity of health care providers to deliver clinical preventive
      services. This study was designed to evaluate the program's effectiveness when
      applied to family physicians in private practice settings. METHODS: Eight
      Midwestern practices that had purchased PPIP kits were identified and agreed to
      participate in the study. A comparative case study approach encompassing a
      variety of data collection techniques was used. These techniques included
      participant observation of clinic operations and patient encounters,
      semistructured and key informant interviews with physicians and staff members,
      chart reviews, and structured postpatient encounter and office environment
      checklists. Content analysis of the qualitative data and construction of the
      individual cases were done by consensus of the research team. RESULTS: PPIP
      materials are not being used, even by the clinics that ordered them. Physicians
      already providing quality preventive services prefer their existing materials to
      those in the PPIP kit. Sites that are underutilizing preventive services are
      unable or unwilling to independently implement the PPIP program. CONCLUSIONS:
      Development of technical support may facilitate implementation of PPIP materials
      into those practices most deficient in providing preventive services. Given the
      diversity of practice environments it is unlikely that a "one size fits all"
      approach will ever be able to address the needs of all providers.

PMID- 8874372
TI  - The effect on metabolic control of second-generation sulfonylurea drugs in
      patients with NIDDM after secondary failure to first-generation agents.
AB  - BACKGROUND: The literature contains few data examining the results of therapy
      with second-generation sulfonylurea drugs in subjects with non-insulin-dependent
      diabetes mellitus (NIDDM) after the onset of secondary failure to first
      generation agents. The present study was undertaken to assess the efficacy of
      therapy with second-generation sulfonylurea in subjects with NIDDM following
      secondary failure to first-generation agents. METHODS: The study included 55
      subjects with NIDDM who manifested secondary failure to first-generation
      sulfonylurea therapy. Of these, 29 subjects underwent therapy with the second
      generation sulfonylurea glipizide, and 26 subjects were treated with glyburide,
      both drugs administered in the maximum daily dosage. Before initiation of the
      second-generation sulfonylurea agents and again at the end of 6 months, metabolic
      control was assessed by determination of fasting plasma glucose, glycosylated
      hemoglobin (HbA1c), and the lipid profile. RESULTS: Fasting plasma glucose and
      HbA1c levels were 209 +/- 31 mg/dL and 12.3 +/- 2.1%, respectively, before
      initiation of glipizide, and did not significantly change following therapy
      (fasting plasma glucose, 211 +/- 34 mg/dL; HbA1c, 11.7 +/- 1.8%). Similarly, no
      significant alteration was noted in these metabolic values in the glyburide group
      (before glyburide therapy, fasting plasma glucose, 180 +/- 16 mg/dL; HbA1c, 11.2
      +/- 1.6%; after glyburide therapy, fasting plasma glucose, 184 +/- 20 mg/dL;
      HbA1c, 11.0 +/- 1.5%). Lipids also were not significantly altered following
      therapy with either glipizide or glyburide. Finally, for all subjects, fasting
      plasma glucose and HbA1c were 200 +/- 27 mg/dL and 11.9 +/- 2.0%, respectively,
      during treatment with first-generation drugs and did not change significantly
      following therapy with the second-generation agents (fasting plasma glucose, 205
      +/- 20 mg/dL; HbA1c, 11.2 +/- 1.2%). P values were > .60 for all comparisons.
      CONCLUSIONS: Treatment with second-generation sulfonylurea agents for patients
      with NIDDM following onset of secondary failure to first-generation sulfonylurea
      drugs achieves no better metabolic control than treatment with first-generation
      agents.

PMID- 8874373
TI  - Do adolescents want to hear preventive counseling messages in outpatient
      settings?
AB  - BACKGROUND: In response to the high prevalence of health-risk behaviors among
      adolescents, policy agencies have urged primary care clinicians to discuss these
      behaviors with all adolescents. Yet such discussions frequently do not take
      place. A commonly mentioned barrier is the clinician perception that patients are
      not interested in, or are embarrassed by, such discussions. The purpose of this
      study was to assess the accuracy of this perception by conducting a survey of
      adolescents. METHODS: Self-administered questionnaires were distributed to 305
      adolescents, ages 11 to 16 years, waiting to be seen in three community health
      centers and three private practices. The questionnaire queried adolescents'
      willingness to talk about eight preventive counseling topics with health care
      practitioners, and information was collected on variables that might influence
      willingness. Descriptive frequencies were generated. Chisquare analysis and
      stratification assessed differences between groups. RESULTS: A majority of
      adolescents felt that it is a clinician's job to discuss health risk behaviors.
      On the current visit, however, fewer than 20% wanted to talk about drugs,
      alcohol, cigarettes, or depression; fewer than 40% about sex; and fewer than 55%
      about diet or exercise. Adolescents reporting previous conversations on a topic
      were more likely to want to talk about that issue at the current visit.
      Willingness to talk did not vary by visit type (well care vs acute care).
      CONCLUSIONS: This study confirms that adolescents are hesitant to discuss health
      risk behaviors with clinicians, but the findings also suggest that receptivity
      increases if clinicians address these topics on repeat occasions.

PMID- 8874374
TI  - Management of gestational diabetes by family physicians and obstetricians.
AB  - BACKGROUND: Studies suggest that there are differences between family physicians'
      (FPs) and obstetricians' (OBs) management of women with low-risk pregnancies.
      This study was conducted to examine outcomes in women with gestational diabetes
      mellitus (GDM) to see if similar patterns exist between those cared for by FPs
      and those cared for by OBs. METHODS: A retrospective chart review was undertaken
      and analyzed by prenatal care provider. Eight hundred thirteen women were
      identified as having a pregnancy complicated by GDM. Management outcome data of
      FPs and OBs were compared. RESULTS: Eighteen percent of patients were cared for
      by FPs. The percentage with a prior history of GDM did not differ between groups.
      Patient groups were similar demographically except that FPs cared for a
      significantly higher percentage of patients on public assistance (60% vs 38%, P <
      .001). Average prepregnancy weight and body mass index were equal, as were
      average weight gain, gestational week at entrance to care, and number of prenatal
      visits. Class instruction on diabetes was given to 83% of FP patients and 85% of
      OB patients. A greater percentage of OB patients were placed on insulin therapy
      (33% vs 24%, P < .05). Complications of pregnancy, labor, and delivery were
      equal, but a higher number of OB patients had a cesarean section (33% vs 11% for
      FPs). Despite the equal occurrence of preterm labor/delivery and low birthweight,
      OBs used tocolysis in significantly more women than did FPs (10.3% vs 4.7%, P <
      .03). Average birthweight of infants delivered by FPs and OBs (3259 g and 3356 g,
      respectively), macrosomia rate (12% and 13%, respectively), length of pregnancy,
      fetal complication rate, Apgar scores, and length of hospital stays were all
      equivalent. CONCLUSIONS: Although there are variations in the care of women whose
      pregnancy is complicated by gestational diabetes mellitus, there are no
      significant differences in neonatal outcome. There is, however, an overall lower
      rate of both cesarean section and tocolysis use among women cared for by FPs.

PMID- 8874375
TI  - Recruitment of private practices for primary care research: experience in a
      preventive services clinical trial.
AB  - BACKGROUND: Recruitment of community primary care practices for studies to
      improve health service delivery is important to many health care organizations.
      Prior studies have focused on individual physician recruitment or academic
      settings. METHODS: This descriptive study evaluated the efficiency and utility of
      three different recruitment methods to encourage community practice participation
      in a preventive services research trial. Primary care practices in four
      midwestern states were recruited using different sources for initial mailings
      (physician lists, practice lists, and a managed care organization's primary care
      network) and different recruiting methods. Outcome measures included response
      rates, participation rates, and comparative costs of each method. RESULTS: Of the
      86 eligible practices contacted, 52 (60%) consented to participate. Mailing to
      individual physicians was the most cumbersome and expensive method and had the
      lowest response rate. Initial contacts with practice medical directors increased
      the participation rate substantially, and practice recruitment meetings improved
      both study participation and practice-project communication. CONCLUSIONS:
      Experience with these three methods suggests that the most efficient way to
      recruit practices for participation in a preventive services research trial
      involves targeted mailings and phone calls to medical directors, followed by on
      site practice meetings.

PMID- 8874376
TI  - Late psychological sequelae of abortion: questions from a primary care
      perspective.
AB  - Research strongly supports the view that pregnancy termination is seldom
      associated with adverse psychological sequelae in the short to medium term, but
      experience shows that there is a small group of women who experience long and
      intense suffering. This is a report of the cases of two women who presented with
      psychological problems associated with a termination 19 and 5 years earlier.

PMID- 8874377
TI  - My first cricothyrotomy.

PMID- 8874378
TI  - In situ localization of tissue factor in human atherosclerotic plaques by binding
      of digoxigenin-labeled factors VIIa and X.
AB  - The mechanism responsible for the thrombotic complications of atherosclerotic
      plaques is not well understood. Although a role for tissue factor (TF) has been
      hypothesized, there are scant data on the presence, location, quantity, and
      activity of TF in atherosclerotic plaques. The purpose of this study was to show
      the localization of TF in human atherosclerotic plaques. Digoxigenin-labeled
      factors VIIa and X were used to demonstrate their specific binding sites in
      formalin-fixed, paraffin-embedded human arteries by incubation of sections with
      the labeled factor and localization of TF:factor(s) complexes by
      immunohistochemical staining for digoxigenin. In sections of atherosclerotic
      plaques, diffuse staining was most intense in the relatively acellular, lipid
      rich core but was also present intracellularly in macrophages and smooth muscle
      cells and, to a lesser extent, in the relatively acellular fibrous tissue of the
      plaque. Endothelial cells overlying plaques and occasional medial smooth muscle
      cells stained positively as well. The adventitia routinely stained for TF in both
      normal and diseased artery segments. Staining for labeled factor VIIa was blocked
      when sections were preincubated with a 10-fold excess of unlabeled factor VIIa or
      with a polyclonal antihuman TF antibody. Binding of labeled factors VIIa and X
      was Ca(2+)-dependent. In conclusion, binding of digoxigenin-labeled factors VIIa
      and X shows that the lipid rich core of atherosclerotic plaques contains high
      levels of extracellular TF. This location may be responsible for the rapid
      initiation of thrombosis when lipid rich atherosclerotic plaques rupture and the
      core contents are exposed to flowing blood.

PMID- 8874379
TI  - Prolonged cytokine exposure causes a dynamic redistribution of endothelial cell
      adhesion molecules to intercellular junctions.
AB  - After 4 hours of treatment with TNF, newly synthesized endothelial leukocyte
      adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular
      adhesion molecule 1 molecules are diffusely expressed on the apical surface of
      cultured umbilical vein endothelial cells. Such cells maintain the epithelioid,
      cobblestone appearance of untreated endothelial cells and display cytoskeletal
      actin largely arranged in dense peripheral bands. After 24 to 72 hours of
      treatment with TNF, cells become elongated and rearrange their actin filaments
      into longitudinal stress fibers. At this time, intercellular adhesion molecule 1
      and vascular cell adhesion molecule 1 remain elevated but redistribute to the
      cell junctions. Intercellular adhesion molecule 2, beta 1 integrins, and beta 3
      integrins also redistribute to cell junctions in TNF-treated cultures. IFN-gamma
      produces morphologic changes similar to those induced by TNF but does not cause
      surface protein redistribution. Cells treated with TNF plus IFN-gamma become even
      more elongated and display TNF-like redistributions. We conclude that TNF
      activates a program of membrane protein redistribution, and we speculate that
      this dynamic redistribution of adhesion molecules to cell junctions may
      contribute to the recruitment of leukocytes to sites of inflammation.

PMID- 8874380
TI  - Interphase cytogenetic analysis of serous ovarian tumors of low malignant
      potential: comparison with serous cystadenomas and invasive serous carcinomas.
AB  - The cytogenetic and molecular genetic changes in serous tumors of low malignant
      potential (LMP) of the ovary have not been well characterized so far. Therefore,
      we analyzed 20 serous tumors of LMP, 10 invasive serous ovarian carcinomas, and 7
      benign serous cystadenomas by nonisotopic in situ hybridization (seven different
      centromere-specific probes) as well as by flow and image DNA cytometry and
      compared the data with results of p53 and Ki67 immunohistochemistry, MYC DNA PCR
      analysis and with the clinical follow-up. All but two tumors of LMP were DNA
      cytometrically diploid; 9 of 10 invasive carcinomas proved to be DNA nondiploid
      (p < 0.0001). Nonisotopic in situ hybridization revealed a mean number of 1.5
      chromosomal aberrations in tumors of LMP, which differed statistically
      significantly from cystadenomas (mean, 0.4) and from invasive carcinomas (mean,
      3.4) (rho < 0.01). The main changes in tumors of LMP were +6 (7 of 18 cases) and
      +7 (6 of 19) followed by -3 (5 of 20), -1 (4 of 17) and +X (3 of 20). In the
      group of invasive carcinomas, the number of cases with signal gains for
      chromosomes 6 (5 of 8), 7 (7 of 10) and X (4 of 10) and signal loss for
      chromosome 1 (4 of 9) was even larger. In addition, statistically significantly
      more cases showed gain of 8 (5 of 10) and loss of 17 (5 of 10) (p < 0.05).
      Proliferative activity (Ki67 index) was positively correlated with the number of
      chromosomal aberrations (p < 0.05). There was no association between changes in
      the centromere signal number of chromosomes 8 and 17 and MYC DNA amplification
      and immunohistochemical p53 accumulation, respectively. Clinical follow-up showed
      prognostic differences between tumors of LMP and invasive carcinomas as expected
      (rho < 0.001) but did not reveal differences within the group of tumors of LMP
      with regard to the number or type of the chromosomal abnormalities detected. In
      conclusion, the patterns of chromosomal gains and losses in serous tumors of LMP
      and invasive serous carcinomas of the ovary do not seem random and suggest a
      close relation between these neoplasms compatible with sequential stages in a
      multistep model of ovarian carcinogenesis.

PMID- 8874381
TI  - Gene transfer of naked DNA encoding for three isoforms of vascular endothelial
      growth factor stimulates collateral development in vivo.
AB  - Vascular endothelial growth factor (VEGF) is a naturally secreted endothelial
      cell-specific mitogen. We investigated the hypothesis that naked DNA encoding for
      VEGF could be used in a strategy of arterial gene therapy to stimulate collateral
      artery development. Plasmid DNA encoding each of the three principal human VEGF
      isoforms (phVEGF121, phVEGF165, or phVEGF189) was applied to the hydrogel polymer
      coating of an angioplasty balloon and delivered percutaneously to one iliac
      artery of rabbits with operatively induced hindlimb ischemia. Compared with
      control animals transfected with LacZ, site-specific transfection of phVEGF
      resulted in augmented collateral vessel development documented by serial
      angiography, and improvement in calf blood pressure ratio (ischemic to normal
      limb), resting and maximum blood flow, and capillary to myocyte ratio. Similar
      results were obtained with phVEGF121, phVEGF165, and phVEGF189, which suggests
      that these isoforms are biologically equivalent with respect to in vivo
      angiogenesis. The fact that viral or other adjunctive vectors were not required
      further suggests that secreted gene products may have potential therapeutic
      utility even when the number of successfully transfected cells remains low.
      Arterial gene transfer of naked DNA encoding for a secreted angiogenic cytokine,
      thus, represents a potential alternative to recombinant protein administration
      for stimulating collateral vessel development.

PMID- 8874382
TI  - In vitro production and transplantation of immunologically active skin
      equivalents.
AB  - In this study, we produced in vitro epidermal equivalents (EE) and skin
      equivalents (SE) with and without spleen lymphocytes. These skin substitutes were
      used for in vitro and in vivo (after isograft) histologic studies of cell and
      extracellular matrix organization and for protein synthesis. Then, using spleen
      lymphocytes in syngeneic and allogeneic SE, we assessed the immunogenicity of
      these skin substitutes after transplantation. In vitro histologic analyses showed
      that the epidermal organization of EE was comparable to that of SE. Fibroblasts
      and spleen lymphocytes were present in the extracellular matrix, as is the case
      in normal skin. Comparative immunohistologic studies after EE and SE isografting
      showed that the newly generated cutaneous tissues were well structured and
      vascularized. There were indications of physiologically active skin. The dermal
      component in these regenerated skins was, however, more organized after SE than
      after EE isografting, which indicates the importance of the dermis. Lastly,
      allografting of SE with and without spleen lymphocytes showed interesting
      results. Indeed, 10 days after allografting, all SE allowed skin regeneration
      comparable to isografts. Moreover, leukocyte infiltration in allografts was
      observed as early as 10 days and increased during the postgrafting period. Also,
      the presence of allogeneic spleen lymphocytes alone in syngeneic SE initiated
      recipient immune activation and induced leukocyte infiltration and graft
      rejection. The density of infiltrating leukocytes was higher in the complete
      allograft (allogeneic keratinocytes, fibroblasts, and spleen lymphocytes)
      compared with the partial allograft (only spleen lymphocytes were allogeneic),
      with the allograft (allogeneic keratinocytes and fibroblasts), and with the
      partial isograft (presence of syngeneic lymphocytes with allogeneic keratinocytes
      and fibroblasts). Mac-1+ and CD8+ cells were present in these leukocyte
      infiltrations, which indicates recipient immune system activation and allograft
      rejection. CD4-positive cells were not, however, seen in these leukocyte
      infiltrations. These results suggest that the incorporation of spleen lymphocytes
      in SE enhanced their immunogenicity as judged by leukocyte infiltration and the
      presence of CD8+ cells in the implants.

PMID- 8874383
TI  - p53 mutations in Hodgkin's disease.
AB  - Although numerous studies have demonstrated increased expression of p53 protein
      in the Reed-Sternberg cells of Hodgkin's disease, little data exist as to whether
      mutations of the p53 gene is a common occurrence in this neoplasm. Using a
      microdissection technique coupled with PCR, single-strand conformation analysis,
      and DNA sequencing, we studied 23 cases of Hodgkin's disease for mutations within
      exons 5 to 8 of the p53 gene. We found seven mutations within six cases; six were
      missense mutations. An identical missense mutation was found in three cases
      (codon 243, methionine to isoleucine), and another identical missense mutation
      was found in an additional two cases (codon 204, glutamic acid to lysine).
      Verification of the mutations was accomplished either by direct Southern blotting
      of PCR-amplified p53 exon products from re-extracted DNA or by hybridization of
      cloned PCR-amplified p53 exon products from re-extracted DNA with a mutant
      specific oligonucleotide. There was no good correlation between the presence of
      p53 mutations and the level of p53 protein expression, which was found to be
      overexpressed in all cases, the level of MDM2 protein expression, or the
      proliferation rate as determined by K-67 antibody. None of the cases with p53
      mutation had evidence of Epstein-Barr virus within the Reed-Sternberg cells, as
      compared with 7 of 17 of the other cases (p < 0.06). These results suggest that
      p53 mutation may represent an important mechanism in the pathogenesis of
      Hodgkin's disease, and this mechanism may be independent of Epstein-Barr virus.

PMID- 8874384
TI  - Interleukin-4, transforming growth factor beta 1, and dexamethasone inhibit
      superantigen-induced prostaglandin E2-dependent collagenase gene expression
      through their action on cyclooxygenase-2 and cytosolic phospholipase A2.
AB  - Signalling via MHC class II in human fibroblast-like synoviocytes selectively
      induces interstitial collagenase gene expression over its natural inhibitor, the
      tissue inhibitor of metalloproteinase (TIMP), through a prostaglandin E2 (PGE2)
      dependent pathway involving cyclooxygenase-2 (COX-2) and cytosolic phospholipase
      A2 (cPLA2). In the present study, we investigated the effect of three different
      agents the T-cell-derived cytokine IL-4, transforming growth factor beta 1 (TGF
      beta 1), and dexamethasone (DXS) on this response. Our results indicate that
      treatment of superantigen-stimulated synoviocytes with DXS or IL-4 inhibited
      collagenase gene expression without affecting TIMP gene expression. In contrast,
      treatment of superantigen-stimulated synoviocytes with TGF-beta 1 resulted in an
      inhibition of collagenase induction and an increase in TIMP gene expression. IL
      4, TGF-beta 1, and DXS abolished PGE2 production and the expression of COX-2 and
      cPLA2 but failed to affect the constitutive expression of COX-1 and secreted
      PLA2. Moreover, all agents abolished protein production and phosphorylation of
      COX-2 and cPLA2, respectively. The inhibitory effect of the three agents on
      collagenase gene expression was partially reversed by exogenous PGE2, which
      confirms that major histocompatibility complex class II-induced collagenase gene
      expression is regulated through a PGE2-mediated pathway. These data highlight a
      mode of action of a classical anti-inflammatory agent (DXS) and of two cytokines
      with recognized anti-inflammatory characters (IL-4 and TGF-beta 1) on a major
      histocompatibility complex class II-induced response and support the involvement
      of COX-2 and cPLA2 in major histocompatibility complex class II-induced
      interstitial collagenase production in human fibroblast-like synoviocytes.

PMID- 8874385
TI  - A novel in vitro assay for human angiogenesis.
AB  - Angiogenesis, the development of new blood vessels, is an important process in
      tissue development and wound healing but becomes pathologic when associated with
      solid tumor growth, proliferative retinopathies, and rheumatoid arthritis. To
      date, there has not been a physiologically relevant in vitro model for human
      angiogenesis that can be used to screen for enhancers and inhibitors of human
      angiogenesis and allow further investigation of this process. Initially, culture
      conditions were established for the induction of human angiogenesis in vitro
      using fragments of human placental blood vessel. Once the assay was validated, it
      was examined for its ability to detect known inhibitors and enhancers of
      angiogenesis. The role of endogenous acidic fibroblast growth factor (aFGF),
      basic fibroblast growth factor (bFGF), and vascular endothelial growth factor
      (VEGF) in the angiogenic response was also assessed by performing RT-PCR on both
      the parent vessel and microvessel outgrowths. In addition, neutralizing
      antibodies against the three growth factors were used to quantify the relative
      importance of each growth factor in the angiogenic response. A fragment of human
      placental blood vessel was embedded in a fibrin gel in microculture plates and
      was found to give rise to a complex network of microvessels during a period of 7
      to 21 days in culture. The response did not require the addition of exogenous
      growth factors, and thus provides a convenient system for testing substances for
      their ability to stimulate or inhibit a human in vitro angiogenic response. The
      ability of the well known angiogenesis antagonist, hydrocortisone, in the
      presence and absence of heparin, and suramin to significantly inhibit the
      angiogenic response indicated that the model could be used as an efficient in
      vitro assay for screening inhibitors of human angiogenesis. The presence of mRNA
      for aFGF, bFGF, and three isoforms of VEGF, as well as their receptors, FGFR1,
      FGFR2, Flt-1, and KDR, in vessel outgrowths and the parent vessel, as identified
      by RT-PCR, strongly implicated aFGF, bFGF, and VEGF as having an important role
      in this neovascularization response. This was further confirmed by the ability of
      neutralizing antibodies to aFGF, bFGF, and VEGF to inhibit the angiogenic
      response to varying extent. Furthermore, the response could be enhanced by the
      addition of these growth factors in serum-starved cultures. Finally, a
      stimulatory effect was observed when matrigel was incorporated into the fibrin
      gel, which indicates that components of the extracellular matrix also play an
      important role in governing the strength of the angiogenic response. A
      physiologic angiogenic response relevant to wound healing can be generated by
      culturing fragments of human placental blood vessels in fibrin gels. The growth
      factors aFGF, bFGF, and VEGF were shown to play an important role in stimulating
      this spontaneous angiogenic response. This assay, which can be performed in
      microcultures, was also shown to be an excellent method for screening for
      potential inhibitors and enhancers of human angiogenesis.

PMID- 8874386
TI  - Melatonin in human breast cancer tissue: association with nuclear grade and
      estrogen receptor status.
AB  - The pineal hormone melatonin has been reported to inhibit tumor growth in a
      variety of experimental and clinical situations and to be an important
      immunoregulatory agent. Cancer patients with mammary or prostate tumors show
      reduced levels of circulating melatonin. Melatonin might, thus, be involved in
      the development of the malignant disease and act directly on tumor cells.
      Melatonin concentration in human neoplastic and adipose tissue sampled from
      mastectomy or tumorectomy products (n = 15) was measured by high-performance
      liquid chromatography. Melatonin seemed to be 3 orders of magnitude more
      concentrated in the neoplastic and adipose tissues of the breast than in sera
      from healthy subjects or cancer patients. Few samples (n = 3) of normal breast
      tissues showed equally elevated concentrations of melatonin. Most interestingly,
      we found a significant inverse correlation between nuclear grade and melatonin
      concentration (p < 0.006) and a positive association between melatonin and
      estrogen receptor status (p < 0.02). No correlation between age of the patients
      and melatonin concentration was evident. Melatonin might be produced in situ by
      mammary epithelial cells and represent a good prognostic marker. The possibility
      that exogenous melatonin might influence nuclear grade and/or estrogen receptor
      activity in breast cancer patients should be investigated.

PMID- 8874387
TI  - Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a
      murine model.
AB  - Integrin alpha v beta 3 is differentially expressed in angiogenic blood vessels
      in skin granulation tissue, and alpha v beta 3 antagonists inhibit angiogenesis
      in chick chorioallantoic membranes. In this study, we investigated the role of
      alpha v beta 3 in retinal neovascularization. There was no detectable signal for
      alpha v beta 3 by immunohistochemistry in normal human retina, but neovascular
      tissue removed from the surface of the retina of patients with diabetic
      retinopathy showed intense staining for alpha v beta 3 within the endothelial
      cells of new blood vessels. In a murine model of oxygen-induced ischemic
      retinopathy, there was intense staining for alpha v beta 3 in endothelial cells
      participating in neovascularization but no detectable staining in normal retinal
      blood vessels of adult mice. Synthetic peptides that bind alpha v beta 3 and
      perturb alpha v beta 3-mediated adhesion in vitro inhibited retinal
      neovascularization in the murine model when given by intraperitoneal or
      periocular injections. These data suggest that alpha v beta 3 antagonists may
      provide a useful adjunct for the treatment of retinal neovascularization.

PMID- 8874388
TI  - Molecular epidemiology of deletions and mutations of the latent membrane protein
      1 oncogene of the Epstein-Barr virus in posttransplant lymphoproliferative
      disorders.
AB  - Latent membrane protein 1 (LMP1) is a protooncogene of the Epstein-Barr virus
      (EBV) that is expressed in most EBV-positive posttransplant lymphoproliferative
      disorders (PTLD). Small deletions in the carboxy-terminal domain of LMP1 have
      been recently described in Hodgkin's disease, nasopharyngeal carcinoma, and non
      Hodgkin's lymphoma. We characterized the deletions and point mutations of LMP1 in
      32 PTLD and 8 reactive lymphoid cases found to contain EBV by one or more
      methods, including LMP1 immunohistochemistry, EBV-encoded RNA in situ
      hybridization, LMP1 DNA amplification, or Southern blot analysis. Our goal was to
      study the relationship of LMP1 deletions and mutations with the PTLD morphology,
      clonality, EBV strain subtype, and survival of patients. We found a 30-bp
      deletion (Del-LMP1) in 13 of 32 (41%) PTLD cases and a similar incidence of Del
      LMP1 and point mutations in 3 of 8 (38%) reactive EBV cases (rho = 0.87). The
      presence of the Del-LMP1 in the PTLD cases was not highly associated with a high
      grade morphology or clonal immunoglobulin gene rearrangements compared with the
      wild-type LMP1. We found that 100% of B-strain isolates, compared with 30% of A
      strain isolates, harbored the Del-LMP1. There was no significant difference in
      the survival of PTLD patients with or without Del-LMP1 (rho = 0.83). We conclude
      that the incidence of Del-LMP1 in PTLD may be reflective of the incidence of this
      EBV substrain in the regional population and that the Del-LMP1 sequence has no
      prognostic significance in PTLD.

PMID- 8874389
TI  - Aberrant expression of a hemidesmosomal protein, bullous pemphigoid antigen 2, in
      human squamous cell carcinoma.
AB  - Through yet unidentified mechanisms, squamous epithelial cells become committed
      to terminal differentiation after detachment from the basement membrane. In
      squamous cell carcinoma, these mechanisms seem to be disturbed. A murine
      monoclonal antibody, designated NCC-Lu-226 (IgG1, K), which recognizes an antigen
      expressed in basal cells of squamous epithelium at the epithelio-connective
      tissue border, was obtained. A cDNA clone encoding the antigen was isolated from
      a cDNA library by immunoselection. DNA sequencing and a database search revealed
      that this cDNA clone was identical to a hemidesmosomal transmembrane protein,
      bullous pemphigoid antigen 2 (BPA-2; also known as BPAG2, BP180, or type XVII
      collagen). Immunoelectron microscopy validated the specific reactivity of this
      monoclonal antibody with skin hemidesmosomes. Enhanced expression and abnormal
      distribution of BPA-2 was revealed immunohistochemically in various precancerous
      and cancerous tissues, including solar keratosis (4 of 5), Bowen's disease (3 of
      5), invasive squamous cell carcinoma (7 of 7) of the skin, and squamous cell
      carcinoma of the lung (14 of 14), esophagus (12 of 13), and cervix (14 of 17).
      The specific expression of BPA-2 protein in squamous cell carcinoma was confirmed
      by RT-PCR and Northern hybridization. BPA-2 has possible phosphorylation sites
      and is actually phosphorylated in cultured keratinocytes and squamous cell
      carcinoma. The aberrant expression of BPA-2 may reflect dysfunction of the
      hemidesmosome that occurs as a relatively early event in multistep carcinogenesis
      of squamous epithelium.

PMID- 8874390
TI  - Apoptosis of hair follicle cells during doxorubicin-induced alopecia in rats.
AB  - Alopecia is a common side effect of cancer chemotherapy, and to date, little
      progress has been made in alopecia prevention or treatment. The present studies
      were undertaken to topographically localize the site of injury in the hair
      follicle after doxorubicin (DXR) administration and to investigate the mechanism
      of DXR-induced alopecia. Tissue samples of head and proximal neck skin obtained
      from newborn rats treated with DXR were histologically examined by light and
      electron microscopy and stained by the terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick-end labeling method. Light microscopy
      revealed pyknotic cells in the matrix and in the upper bulb and a decrease in the
      number of mitotic cells. Terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-digoxigenin nick-end labeling analysis evidenced cells
      with nuclear staining indicative of apoptosis, as confirmed by ultrastructural
      analysis. Kinetics studies indicated that even a single DXR treatment induced
      apoptosis and a decrease in mitotically active cells. Our data show that DXR
      treatment induces injury in a cell subset localized in the hair matrix. The
      successful prevention of drug-induced alopecia in patients may depend on the
      selective protection of these cells of the hair follicle.

PMID- 8874391
TI  - Detection of micrometastases in colorectal cancer patients by K19 and K20 reverse
      transcription polymerase chain reaction.
AB  - Tumor stage in bowel and breast cancer is the chief determinant of prognosis and
      the need for adjuvant therapy. The intermediate filament protein keratin 19 (K19)
      is expressed by epithelia and corresponding malignancies. Recently, the detection
      of K19 gene expression by RT-PCR has been reported as a sensitive tool for
      detecting occult metastasis to the lymph nodes and bone marrow of patients with
      primary epithelial tumors. Doubt has arisen, however, about the tissue
      specificity of K19 gene expression. In this study, we report a comparison of RT
      PCR for K19 with another keratin, K20, in the lymph nodes and bone marrow of 15
      patients with colorectal cancer, eight control patients who underwent bowel
      resection for benign disease, and four other control patients. K19 and K20 gene
      expression was detected in 84 and 26 of 109 lymph nodes and in 6 and 0 of 15 bone
      marrow aspirates, respectively, from colorectal cancer patients. K19 gene
      expression was also detected in 34 of 40 lymph nodes and in 5 of 12 bone marrow
      aspirates from control patients, whereas K20 gene expression was undetectable in
      any control sample. In conclusion, K19 RT-PCR lacks specificity as a marker of
      occult lymph node and bone marrow metastasis. In contrast, K20 RT-PCR was
      specific and should be evaluated further in future studies.

PMID- 8874392
TI  - Dehydroepiandrosterone (DHEA).

PMID- 8874393
TI  - Drugs for chronic heart failure.

PMID- 8874394
TI  - Behavior of the H-reflex in humans following mechanical perturbation or injury to
      rostral spinal cord.
AB  - In humans H-reflexes are suppressed during early spinal shock. In animals rostral
      cord injury results in loss of segmental reflexes within seconds. If H-reflexes
      persist under general anesthesia, can they be used to monitor the integrity of
      the rostral cord? In part I of this study, we recorded H-reflexes
      intraoperatively in 25 patients to elucidate general anesthesia effect. In 23
      subjects, H-reflexes were consistently elicited, and within +/- 13% of the
      normalized group mean amplitude. In part II, we recorded H-reflexes in 31
      patients during spinal cord surgery to elucidate H-reflex behavior immediately
      following rostral spinal cord injury. In 6, abrupt suppression of the H-reflex
      coincided with cord injury. In 4 of 6, suppression was transient and less than
      50% of baseline; none of these patients developed neurological deficits. In 2,
      suppression exceeded 90% and persisted throughout surgery; both patients
      developed profound deficits. We conclude that (1) the H-reflex can be
      consistently elicited under general anesthesia in most patients, (2) rostral cord
      injury rapidly suppresses the H-reflex, and (3) the degree and duration of H
      reflex suppression reflects the severity of the injury.

PMID- 8874395
TI  - Remodeling of the cytoskeletal lattice in denervated skeletal muscle.
AB  - The effect of denervation-induced atrophy on the cytoskeletal lattice in rat fast
      and slow-twitch skeletal muscle has been investigated. Immunochemical analyses
      and immunofluorescence microscopy experiments employing monospecific antibodies
      to dystrophin, desmin, and alpha-tubulin were carried out on intact and
      denervated muscles. The relative cellular content of dystrophin and desmin were
      reduced in the soleus muscle (slow-twitch), while significant increases were
      shown in the gastrocnemius muscle (fast-twitch). In both muscles, alpha-tubulin
      levels increased up to 12-fold as a function of time compared to control values.
      Immunofluorescence microscopy revealed a distinct rearrangement of the
      microtubule network toward a predominantly longitudinal alignment, which was
      accompanied by an increase in the density of the fluorescence. It is concluded
      that the relative increase of the three structural proteins in the fast-twitch
      gastrocnemius muscle may be related to the apparent resistance of this muscle
      type to denervation-induced atrophy. The increased alpha-tubulin content in
      denervated slow- and fast-twitch muscles could be indicative of an adaptive
      mechanism designed to maintain the integrity of the muscle fiber in view of
      eventual regenerative activities.

PMID- 8874396
TI  - Electrical and mechanical properties of skeletal muscle underlying increased
      fatigue in patients with amyotrophic lateral sclerosis.
AB  - To investigate the mechanical efficiency of surviving motor units of anterior
      tibial muscle in patients with amyotrophic lateral sclerosis (ALS), we studied
      motor unit action potentials, muscle force, and muscle fatigability in patients
      with ALS and controls using 25 min of low to moderate intensity voluntary
      isometric exercise. During exercise, tetanic force (TF) and maximum voluntary
      contraction declined more in patients than in controls. The mean motor unit
      action potential duration, amplitude, and polyphasia were increased in patients
      compared to controls but did not change during 9 months of disease progression.
      The enlarged motor units in patients were negatively correlated to the muscle
      force and positively correlated to muscle fatigability. Furthermore, after a mean
      follow-up period of 9 months, the decline in force-generating capacity of the
      anterior tibial muscle in patients (twitch tension by 37.5 +/- 11.2%, TF by 30.6
      +/- 7.4%) was greater than the decline in the amplitude of the compound muscle
      action potential (21.1 +/- 8.8%, P < 0.05), suggesting a relative dissociation
      between electrical and mechanical properties. In conclusion, the enlarged motor
      units in patients with ALS are mechanically less efficient and fatigue relatively
      more than in healthy muscles, possibly due to an abnormality that is primarily
      distal to the muscle membrane.

PMID- 8874397
TI  - Coculture of rat embryonic proprioceptive sensory neurons and myotubes.
AB  - With the aim to study the cellular mechanism underlying the process of muscle
      spindle regeneration, dorsal root ganglia (DRG) neurons derived from 16-day rat
      embryos were cocultured with developing myotubes in a compartmentalized culture
      device. To accomplish the selective survival and neurite formation of the
      proprioceptive subpopulation, the neurotrophic factor, neurotrophin-3, was added
      to the culture medium. It appeared that the proprioceptive DRG neurons could
      develop specialized, Ia afferent terminal-like contacts with myotubes. However,
      these interactions were scarce and did not result in the induction of
      differentiation of the contacted myotubes into intrafusal fibers as normally
      occurs during in vivo development. The present coculture setup apparently lacks
      appropriate regulatory factors essential for the proper matching of sensory axons
      and intrafusal fiber precursors and the induction of a functional sensory
      myoneural connection.

PMID- 8874398
TI  - Electrophysiologic and histologic studies in clinically unaffected muscles of
      patients with prior paralytic poliomyelitis.
AB  - Macro-electromyography (macro-EMG) studies have provided important information
      about the size of the motor units and the degree of reinnvervation in clinically
      affected muscles of patients with a history of poliomyelitis and postpolio
      syndrome. The study of clinically unaffected muscles and correlation of their
      electrophysiologic characteristics with the muscle architecture could provide
      meaningful information about the ongoing subclinical denervation. We performed
      macro-EMG and concomitantly measured fiber density in the clinically unaffected
      gastrocnemius muscle of 10 patients with postpolio syndrome and 10 normal
      subjects of similar age. We also performed biopsies on the gastrocnemius muscle
      of 8 of the patients. The median amplitude and area of the macro-motor unit
      potentials (macro-MUPs) were increased in 8 of the 10 patients, and occasionally
      were five times as large as the mean median value for the normal subjects. Seven
      biopsy specimens showed moderate to very large fiber-type grouping. In 5
      patients, there was correlation between the electrophysiologic and histologic
      indices of reinnervation. Amplitude and area of the macro-MUPs were associated
      with the muscle fiber cross-sectional area. We conclude that clinically
      unaffected muscles of patients with postpolio syndrome often have large motor
      units as the result of effective reinnervation after the original motor neuron
      loss. In spite of possible differences in the cytoarchitecture of muscles
      affected to different degrees, macro-EMG and fiber density measurements are
      reliable noninvasive techniques for studying the extent and effectiveness of
      reinnervation in patients with postpolio syndrome.

PMID- 8874399
TI  - Effects of external calcium on contractile responses in rat extensor digitorum
      longus muscles after sciatic nerve injury at birth.
AB  - Two types of nerve lesions were performed at birth in rat extensor digitorum
      longus muscle: sciatic nerve transection (group A) and sciatic nerve crush
      allowing further reinnervation (group B). Contractile responses were then studied
      at different times after the denervation (7, 14, 30, and 60 days) and compared
      with control. Sixty days after the intervention, twitch and tetanic tensions
      remained dependent upon the extracellular Ca2+ concentration ([Ca]o) both in
      groups A and B. However, the depression of tensions following Ca2+ withdrawal was
      more important in group A. Sixty days after birth, in the presence of a Ca2+
      channel blocker, Cd2+ (2 mmol L-1), a depression of the twitch tension was
      observed in group A (similarly to control 1-7 days postnatal muscles), whereas
      Cd2+ potentiated twitch tension in group B (similarly to control 14-60 days
      postnatal muscles). After glycerol treatment (detubulating procedure) performed
      in 60-day-old muscles, twitch tension was abolished in group B and control,
      whereas twitch tension was potentiated in group A. Thus, in developing muscles,
      neural control could be involved in the dependence of contractility toward [Ca]o.
      These results may be relevant for the understanding of the contractile properties
      of neuromuscular disorders with early onset.

PMID- 8874400
TI  - Central fatigue assessed by transcranial magnetic stimulation.
AB  - Central fatigue is a subjective phenomenon which can be examined using
      transcranial magnetic stimulation (TMS). To assess central fatigue, we compared
      TMS and peripheral electrical stimulations in patients with central nervous
      system (CNS) lesions and controls before and after an exhaustive task. The
      recovery times of motor evoked potential (MEP) amplitudes were significantly
      prolonged in the patient group whereas the recovery of F waves and compound
      muscle action potentials showed no significant changes. The results indicate that
      fatigue cannot be attributed either to intramuscular processes or to reduced
      spinal excitability, but reflects a supraspinal, probably cortical phenomenon.
      The measurement of MEP recovery times proved to be a simple and objective tool
      for the assessment of fatigue and for the differentiation between healthy
      controls and patients with CNS lesions.

PMID- 8874401
TI  - Extensive genetic heterogeneity in the "pure" form of autosomal dominant familial
      spastic paraplegia (Strumpell's disease).
AB  - Three dominantly inherited "pure" form of familial spastic paraplegia (FSP) genes
      have been genetically mapped to regions of chromosomes, yet no specific genes or
      mutations have been identified (FSP1; chromosome 14q, FSP2; chromosome 2p and
      FSP3; chromosome 15q). We studied a "pure" form of autosomal dominant FSP family
      from North American of Italian descent for linkage to three dominant FSP loci. We
      excluded all three known loci with markers (D14S288, D14S269, D14S281, D2S352,
      D2S367, D15S210, D15S122, and D15S156) in our "pure" dominant FSP family. Our
      result suggests that dominant FSP is very genetically heterogeneous, and the
      existence of at least a fourth locus (FSP4) for the pure form of autosomal
      dominant FSP (Strumpell's disease).

PMID- 8874402
TI  - Serum of Isaacs' syndrome suppresses potassium channels in PC-12 cell lines.
AB  - Blockage of K+ channels in nerve terminals by immunoglobulin is the speculated
      pathomechanism of Isaacs' syndrome. Using patch-clamp technique (whole-cell
      clamp), we investigated the effects on K+ current of serum taken from 2 patients
      with Isaacs' syndrome employing the clonal cell line PC-12. The addition of a
      patient's serum to the perfusion solution had little effect on the K+ current of
      P-12 cells. In contrast, K+ current was reduced by 25-80% when cells were
      cultured for 3-6 days with 2% serum as compared to control serum values.
      Suppression of the K+ current appears to develop gradually over the period of
      culture. Our results suggest that the pathomechanism of Isaacs' syndrome is
      caused by K+ channel suppression via a humoral factor(s) in the serum, which
      subsequently induces nerve hyperexcitability.

PMID- 8874403
TI  - The histochemistry of reactive masticatory muscle hypertrophy.
AB  - There are two types of hypertrophy of the muscles of mastication in man: reactive
      hypertrophy, the more common form; and nonreactive enlargements-myositic,
      genetic, myopathic, and idiopathic. Reactive hypertrophy develops when the
      masticatory muscle workload is increased by local bone and dental disorders; such
      triggers are not powerful but act over long periods, thus demanding increased
      endurance. Exercise for endurance has a greater effect on the muscles of
      mastication than it has on the large muscles of the limbs; these react solely by
      stimulating the oxidative metabolism of type 1 fibers, whereas masticatory muscle
      reacts structurally by hypertrophy and progressive type 1 fiber predominance.
      Eventually enzyme instability of type 1 fibers and end stage atrophy of type 2
      fibers may appear. Unexpectedly, lesions have also been found in control
      masticatory muscle, in particular type 2 fiber specific atrophy like that seen in
      long-standing acquired autoimmune myasthenia gravis. It is suggested that the
      adverse lesions in hypertrophied and control masticatory muscle are the
      consequence of post-activation fatigue.

PMID- 8874404
TI  - Anatomical and electrophysiological determinants of the human thenar compound
      muscle action potential.
AB  - Clinical interpretation of the compound muscle action potential (CMAP) requires a
      precise understanding of its underlying mechanisms. We recorded normal thenar
      CMAP5 and motor unit action potentials using different electrode configurations
      and different thumb positions. Computer simulations show that the CMAP has four
      parts: rising edge, negative phase, positive phase, and tail which correspond to
      four distinct stages of electrical activity in the muscle: initiation at the end
      plate, propagation, termination at the muscle/tendon junctions, and slow
      repolarization. The shapes of volume-conducted signals recorded beyond the muscle
      are also explained by these four stages. Changes in CMAP shape associated with
      thumb abduction are due to changes in termination times resulting from changes in
      muscle-fiber lengths. These findings demonstrate that the negative and positive
      phases of the CMAP are due to different mechanisms, and that anatomical factors,
      particularly muscle-fiber lengths, play an important role in determining CMAP
      shape.

PMID- 8874405
TI  - Fast-to-slow transformation in stimulated rat muscle.
AB  - Several previous studies have failed to demonstrate changes due to chronic
      stimulation in contractile speed of innervated fast rat muscles, and it has been
      suggested that the adaptive capacity of skeletal muscle in this species is
      limited. We have reassessed this contention. Fast muscles of the rat hind limb
      were stimulated continuously at 10 or 20 Hz for 55-61 days. The maximum
      shortening velocity of the extensor digitorum longus muscles was reduced to 50%
      of the control value. The proportion of type 1 fibers increased from 4% in
      control muscle to 34% in stimulated muscles and there was a corresponding
      reduction in type 2B/D fibers. The proportion of type 2A fibers after stimulation
      was similar to that in control muscles. These results, taken together with our
      published analyses of myosin isoform composition of these muscles, show that the
      mechanisms that control gene expression in response to activity are not exclusive
      to larger mammals.

PMID- 8874406
TI  - Computerized tomography and magnetic resonance muscle imaging in Miyoshi's
      myopathy.
AB  - We describe clinical, pathological, and muscle imaging findings in a patient with
      an early adult-onset progressive muscular weakness in association with atrophy
      beginning in the legs and involving both gastrocnemi in particular. Muscle biopsy
      findings showed a severe dystrophic process with no vacuoles, consistent with
      Miyoshi's myopathy. Computerized tomography and magnetic resonance imaging scans
      were used to provide an ongoing permanent record of the various stages of the
      disease.

PMID- 8874407
TI  - Reproducibility of sympathetic skin response.

PMID- 8874408
TI  - Idiopathic lumbosacral neuropathy: a cause of persistent leg pain.

PMID- 8874409
TI  - Sympathetic skin responses evoked by magnetic stimulation of the neck: normative
      data.

PMID- 8874410
TI  - Immune globulin therapy in children with Guillain-Barre syndrome.

PMID- 8874411
TI  - Muscle shortening, response latency, and conduction velocity.

PMID- 8874412
TI  - American Association of Electrodiagnostic Medicine guidelines for establishing a
      quality assurance program in an electrodiagnostic laboratory. AAEM Professional
      Practice Committee.

PMID- 8874413
TI  - The prevalence of lumbar paraspinal spontaneous activity in asymptomatic
      subjects.

PMID- 8874414
TI  - Frequency of median mononeuropathy in patients with mild diabetic neuropathy in
      the early diabetes intervention trial (EDIT)

PMID- 8874415
TI  - Dermatomal/segmental somatosensory evoked potential evaluation of L5/S1
      radiculopathies.

PMID- 8874416
TI  - Ganciclovir intraocular implant.

PMID- 8874417
TI  - Congenital fibrosis of the extraocular muscles.

PMID- 8874418
TI  - Orbital pseudotumors treated with systemic corticosteroids.

PMID- 8874419
TI  - Orbital pseudotumors treated with systemic corticosteroids.

PMID- 8874420
TI  - PPA: automated lamellar keratoplasty.

PMID- 8874421
TI  - Vertical strabismus after cataract surgery.

PMID- 8874422
TI  - The Registry of Ophthalmic Pathology.

PMID- 8874423
TI  - Hyperopia correction by noncontact holmium:YAG laser thermal keratoplasty. United
      States phase IIA clinical study with a 1-year follow-up.
AB  - PURPOSE: This study was performed to evaluate the safety and effectiveness of
      noncontact holmium: YAG (Ho:YAG) laser thermal keratoplasty (LTK) for correcting
      low to moderate hyperopia. METHODS: Twenty-eight patients were treated
      unilaterally to correct low to moderate hyperopia (up to +3.88 diopters [D]
      refractive error) using simultaneous noncontact delivery of Ho:YAG laser energy.
      Treatment parameters included one or two symmetric octagonal rings of eight spots
      per ring with centerline diameters of 6 mm (1 ring) or 6 and 7 mm (2 rings), ten
      pulses of laser light at 5-Hz pulse repetition frequency, and variable pulse
      energy, ranging from 208 to 242 mJ. Follow-up was 1 year in 26 (93%) of the 28
      patients. RESULTS: At 1 year postoperatively, uncorrected distance visual acuity
      was improved in all patients. The mean change in subjective manifest refraction
      (+/- spherical equivalent [SE]) was -0.55 +/- 0.33 D and -1.64 +/- 0.61 D for one
      and two-ring treatment groups, respectively, with good stability in the
      refractive change after approximately 6 months. In the one-ring treatment group
      (17 eyes), refractive corrections of -0.50 to -1.13 D were achieved in ten eyes
      (59%), and seven eyes (41%) were unchanged (within +/- 0.25 D) relative to their
      preoperative measurements. In the two-ring treatment group, all eight eyes (100%)
      had substantial refractive corrections (range, -0.75 to -2.50 D). Mean induced
      refractive astigmatism was 0.25 +/- 0.29 D and 0.47 +/- 0.53 D for one- and two
      ring treatments, respectively. None of the eyes lost two or more lines of
      spectacle-corrected distance visual acuity. These was no clinically significant
      change in endothelial cell density with respect to preoperative values. Glare and
      contrast sensitivity testing indicate that peripheral corneal opacities produced
      by LTK do not degrade vision. The amount of refractive change in each group was
      correlated with the amount of laser pulse energy. CONCLUSIONS: This initial
      United States clinical study with 1-year follow-up indicates that noncontact LTK
      treatment of low hyperopia is safe and effective, providing persistent, though
      modest, refractive corrections in 59% of the one-ring group and larger,
      persistent, refractive corrections in 100% of the two-ring group.

PMID- 8874424
TI  - Risk factors for retinal detachment after cataract surgery. A population-based
      case-control study.
AB  - PURPOSE: Previous analyses of Medicare claims data, as well as clinical series,
      have suggested that performance of neodymium:YAG (Nd:YAG) laser posterior
      capsulotomy after extracapsular cataract surgery increases significantly the risk
      of retinal detachment. However, methodologic problems with previous research
      limit the strength of conclusions that can be drawn from these earlier studies.
      This study was designed to resolve those methodological limitations while using a
      population-based approach for assessment of the independent association between
      the performance of Nd:YAG laser posterior capsulotomy and pseudophakic retinal
      detachment. METHODS: A nested case-control study was conducted. Medicare
      beneficiaries who had undergone extracapsular cataract extraction from 1988 to
      1990 were identified from a 5% sample of Medicare claims data. Within this
      cohort, people who were diagnosed or treated for retinal detachment during the
      years 1988 through 1991 (cases) were identified from Medicare records. Four
      controls were matched to each case of retinal detachment using an incidence
      density design. Providers of the patients' cataract and retinal surgery were
      contacted and asked to provide clinical data for all cases and controls that they
      had treated. RESULTS: Seven hundred six cases of retinal detachment were
      originally identified from Medicare records. After exclusions due to
      ineligibility, a total of 291 cases and 870 matched controls were available for
      analysis. Conditional logistic regression models showed that a number of factors
      were associated independently with an excess risk of retinal detachment after
      cataract surgery. These included Nd:YAG laser capsulotomy (odds ratio [OR] = 3.8;
      95% confidence interval [CI], 2.4-5.9), a history of retinal detachment (OR =
      2.7; 95% CI, 1.2-6.1), a history of lattice degeneration (OR = 6.6; 95% CI, 1.6
      27.1), axial length (OR = 1.21/mm; 95% CI, 1.03-1.43), refractive error (OR =
      0.92/diopter; 95% CI, 0.88-0.95), and a history of ocular trauma after cataract
      surgery (OR = 6.1; 95% CI, 4.3-28.2). CONCLUSION: Performance of Nd:YAG laser
      posterior capsulotomy is associated with a significantly elevated risk of retinal
      detachment in patients who have undergone extracapsular cataract extraction.
      Other independent risk factors for retinal detachment include axial length,
      myopia, posterior capsular rupture during surgery, history of retinal detachment
      or lattice degeneration, and ocular trauma after cataract surgery.

PMID- 8874425
TI  - Age-related macular degeneration after extracapsular cataract extraction with
      intraocular lens implantation.
AB  - PURPOSE: To evaluate the course of age-related maculopathy after cataract
      surgery. METHODS: Included were 47 patients with bilateral, symmetric, early age
      related macular degeneration (AMD), documented by fluorescein angiography, who
      underwent extracapsular cataract extraction with intraocular lens implantation in
      one eye. The fellow eye served as the control. The patients were retrospectively
      reviewed or prospectively followed. RESULTS: Wet AMD developed in nine eyes
      (19.1%) that were treated with surgery compared with two fellow eyes (4.3%). It
      was detected within 3 months of surgery in four (44.4%) of the nine affected eyes
      and within 6 to 12 months of surgery in four other eyes (44.4%). Progression to
      wet AMD occurred significantly more often in men than in women (P < 0.05). Soft
      drusen were found as a significant ocular risk factor (P < 0.05). The final
      visual outcome was poor in all eyes with such progression. CONCLUSIONS: In this
      study, progression of AMD occurred more often in the surgical eyes compared with
      the fellow eyes. However, the reasons for the progression of AMD after cataract
      surgery are still uncertain. Further prospective studies are needed to
      investigate this observation.

PMID- 8874426
TI  - Irreversible silicone oil adhesion to silicone intraocular lenses. A
      clinicopathologic analysis.
AB  - PURPOSE: To report a newly defined complication of foldable intraocular lenses
      (IOLs), namely silicone oil-silicone IOL interaction. This is a complication not
      generally seen by the implanting cataract surgeon but, rather, at a later stage
      in a patient's postoperative course, by a vitreoretinal surgeon. METHODS: Three
      clinical case histories, including two explanted silicone IOLs, were submitted
      for analysis. The submitted silicone lenses were photographed under water, and
      the nature of the silicone oil coating was documented. RESULTS: In each instance,
      the silicone coating was manifest as a thick coating with droplet formation on
      the lens surface that was tenaciously adherent and could not be dislodged by
      instruments or injection of viscoelastics. CONCLUSION: The use of silicone IOLs
      in patients with current vitreoretinal disease or those who are at high risk for
      future vitreoretinal disease that may require silicone oil as part of the therapy
      should be reconsidered. The authors recommend that information regarding the
      existence and significance of this complication be printed on all silicone oil
      and silicone IOL packages and inserts (if not as a warning, at least as an
      informative comment regarding the existence of this condition). This is a rare
      but clinically significant complication that will affect the occasional patient
      treated with both of these modalities.

PMID- 8874427
TI  - Lens preservation after intraocular foreign body injuries.
AB  - PURPOSE: Ocular missile injuries often involve the lens. Some have suggested that
      lens capsular violation by a foreign body is an indication for immediate lens
      removal. Sometimes, however, the resultant lens opacity may remain localized
      without visual compromise. The authors report a series of patients who had lens
      capsular disruption from an intraocular foreign body that resulted in visually
      insignificant lens opacities. METHODS: A series of five patients with lens
      capsular disruption as a result of an intraocular foreign body injury were
      reviewed retrospectively. RESULTS: All five patients had lens injury from a small
      foreign body in a peripheral lenticular location. In three patients the foreign
      body was intralenticular, whereas in the other two patients the foreign body
      transversed the lens and was located in the posterior segment. In two patients,
      the foreign body was not removed. Three of the patients required pars plana
      vitrectomy. In all patients, final visual acuity was at least 20/40, and the
      lenticular opacity remained localized to an eccentric location. CONCLUSIONS: A
      progressive, visually significant cataract is not the inevitable result of lens
      injury by an intraocular foreign body. When indicated, surgical removal of the
      foreign body may be attempted using a lens-sparing procedure.

PMID- 8874428
TI  - Identifying maculopathy after neodymium: YAG membranotomy for dense diabetic
      premacular hemorrhage.
AB  - PURPOSE: To assess the value of neodymium:YAG membranotomy in achieving rapid
      intravitreal dispersion of dense diabetic premacular hemorrhage and allowing the
      identification and treatment of maculopathy before panretinal photocoagulation
      (PRP). METHODS: A pilot study, in which nine eyes with dense diabetic premacular
      hemorrhages were treated with neodymium:YAG membranotomy, is described. After
      intravitreal dispersion of premacular blood, fundus examination and fluorescein
      angiography were performed to identify neovascularization and macular edema.
      Macular photocoagulation was performed before PRP in eyes with co-existing
      maculopathy and neovascularization. RESULTS: Complete intravitreal dispersion was
      achieved in all eyes within 1 week. Clinically significant macular edema was
      identified and treated, before PRP, in three eyes. No exacerbation of macular
      edema occurred after PRP, and visual acuity was stabilized at pre-hemorrhage
      levels in seven eyes and to within one line in the remaining two eyes. No
      traction retinal detachments or rebleeding occurred, and vitrectomy was not
      required in any eye. CONCLUSIONS: Early neodymium:YAG membranotomy may obviate
      the need for early vitrectomy for dense diabetic premacular hemorrhage, and
      allows early identification and treatment of maculopathy, before PRP, thus
      reducing the risk of exacerbation after PRP. Further studies to evaluate this
      treatment modality, particularly with respect to long-term visual prognosis,
      appear warranted.

PMID- 8874429
TI  - Multicenter clinical experience using an erbium:YAG laser for vitreoretinal
      surgery.
AB  - PURPOSE: To evaluate the advantages, disadvantages, safety, complications, and
      surgical applicability of an erbium:YAG laser system for maneuvers in
      vitreoretinal surgery. METHODS: A prospective, consecutive trial of 68 eyes in 66
      patients undergoing vitreoretinal surgery in which an erbium:YAG laser with
      graduated output from 0.2 to 5.0 mJ per pulse, repetition rate of 2 to 30 Hz, and
      equipped with a flexible fiber optic and interchangeable 20-gauge intraocular
      fiber optic endoprobes was used to perform specific maneuvers, including
      transection, incision, and ablation of membranes, retinotomy, vessel coagulation,
      iridectomy, and lens tissue ablation. The patients were treated in five centers
      in contemporary vitreoretinal surgical settings for surgical indications,
      including proliferative diabetic retinopathy, proliferative vitreoretinopathy,
      epiretinal membrane, and retinopathy of prematurity. RESULTS: One hundred seventy
      four maneuvers were performed with an overall surgical efficacy rating of
      excellent or good in 84% of maneuvers, ranging from a high of 100% for subretinal
      membrane transection to a low of 25% for coagulation of blood vessels.
      Complications included retinal break or photocoagulative injury in 5% of
      epiretinal membrane incisions, minor bleeding from transected retinal vessels
      during 29% of retinotomies, and intraocular lens damage during two posterior
      capsulotomies. The most significant limitation was the cautious pace used during
      maneuvers near the retinal surface. CONCLUSION: The erbium:YAG laser is capable
      of versatile new approaches offering precise tissue cutting and ablation in
      vitreoretinal surgical maneuvers with a high degree of safety. The main
      limitation encountered was the slow speed of certain critical maneuvers near the
      retina.

PMID- 8874430
TI  - Extraocular repeat surgery of retinal detachment. A minimal approach.
AB  - BACKGROUND: After a failed buckle surgery, the second procedure tends to be a gas
      injection and the third a vitrectomy. METHODS: The failures from two series,
      consisting of 752 and 500 buckle surgeries, were analyzed for cause, solution,
      and outcome after repeat surgery with a segmental or encircling buckle. RESULTS:
      The most frequent cause of failure was an undetected break. An analysis of the
      postoperative contour of the detachment suggested its presence and helped to
      locate it. Failure occurred nearly as frequently because the buckle was
      inadequate. It was poorly placed, too narrow, or too shallow. An undetected break
      or an inadequate buckle was the cause of 73% of the failures in the first series
      and 79% of failures in the second series. The failure from either cause
      responded, with few exceptions, to a segmental explant. CONCLUSION: The arbitrary
      sequence of intraocular gas and then vitrectomy in response to failure to attach
      the retina with a scleral buckle often is misdirected.

PMID- 8874431
TI  - Visual acuity impairment in patients with retinitis pigmentosa.
AB  - PURPOSE: The authors evaluated visual acuity impairment in 906 patients from 742
      families with either isolated or various identifiable genetic subtypes of
      retinitis pigmentosa (RP) to determine the severity of their visual acuity
      impairment. Emphasis was placed on the prevalence of total blindness and visual
      acuity of 20/200 or worse in this group of patients. METHODS: This cross
      sectional retrospective study included all patients with RP who met certain
      entrance criteria and were examined by one of the authors (GAF). The authors
      analyzed the eye of each patient with the best-corrected visual acuity on their
      most recent visit. RESULTS: Seventeen patients with a sector form of RP were
      excluded from the authors primary analysis. In the remaining group of 889
      patients, 710 (80%) had a visual acuity of better than 20/200, 648 (73%) showed a
      visual acuity of 20/70 or better, and 489 (55%) had a visual acuity of 20/40 or
      better in at least 1 eye. Seventy-five patients (8%) had visual acuity of count
      fingers or worse in their best eye. There was only one patient with no light
      perception in each eye. Patients with autosomal dominant RP, as a group, had the
      least severe and those with X-linked recessive RP had the most severe impairment
      in visual acuity. Those with autosomal recessive disease were intermediate in
      severity of visual impairment. CONCLUSIONS: Analysis of visual acuity in this
      large group of patients with RP, which genetically is representative of patients
      with RP seen in the United States by those who specialize in retinal disease,
      showed that it was rare for the patients to lose all visual acuity from the
      disease itself. Further, legal blindness from visual acuity loss, defined as best
      corrected visual acuity that is no better than 20/200 in at least one eye,
      occurred in a relatively small percentage (20%) of our patient population,
      whereas approximately half of all patients and 42% of those older than 60 years
      had a visual acuity of 20/40 or better in at least one eye. The extent of
      impairment in visual acuity was associated with the genetic subtype of the
      disease.

PMID- 8874432
TI  - Glandular tumors of the lacrimal sac. Their histopathologic patterns and possible
      origins.
AB  - PURPOSE: To describe and characterize the primary lacrimal sac epithelial tumors
      of glandular origin, and to describe their possible source from glands in the
      lacrimal sac and nasolacrimal duct walls. METHODS: The authors conducted a
      clinicopathologic study on 14 patients with epithelial lacrimal sac tumors of
      possible glandular origin. In addition, they reviewed 35 surgical specimens of
      the lacrimal sac and nasolacrimal duct region and 13 cadaver specimens of the
      lacrimal sac region. RESULTS: Six of the tumors were benign: four were
      oncocytomas and two were pleomorphic adenomas. Eight of the tumors were
      malignant: three were oncocytic adenocarcinomas, three were adenoid cystic
      carcinomas, and two were adenocarcinomas. All tumors were from adults, ranging in
      age from 38 to 87 years. Twenty-eight of the 47 specimens of lacrimal sac and
      nasolacrimal duct region showed mixed glands of serous and mucous elements.
      CONCLUSIONS: Although rare, benign and malignant glandular lacrimal sac tumors
      should be considered in the differential diagnosis of lacrimal sac obstruction.
      Their possible origin is from the normal glands that exist under the lacrimal sac
      and nasolacrimal duct epithelium.

PMID- 8874433
TI  - Tumors arising in the palpebral lobe of the lacrimal gland.
AB  - PURPOSE: Tumors arising in the palpebral lobe of the lacrimal gland are uncommon.
      There have been only eight reported patients, all of whom had pleomorphic
      adenomas. The authors present another six patients with primary palpebral lobe
      tumors. METHODS: The clinical presentation, computed tomographic, and pathologic
      findings of these six patients were reviewed. RESULTS: Tumor types include three
      pleomorphic adenomas, one well-differentiated adenoid cystic carcinoma, one
      carcinoma in pleomorphic adenoma, and one carcinoma ex pleomorphic adenoma. All
      six patients presented with a painless mass in the upper outer eyelid without
      significant displacement of the globe, but the superficial location of these
      lesions led to early detection. The tumors were localized to the lacrimal gland,
      predominantly anterior to the orbital rim. In all six patients, the involved
      palpebral lobe was removed, five via a direct anterior subcutaneous approach and
      one by superolateral orbitotomy. In two patients (adenoid cystic carcinoma and
      carcinoma ex pleomorphic adenoma), repeat surgery via superolateral orbitotomy
      was necessary to achieve complete removal of the lacrimal gland and surrounding
      tissue. No recurrences were detected during follow-up (range, 6 months to 7
      years; mean, 26 months). CONCLUSION: Palpebral lobe tumors of the lacrimal gland
      are more common and consist of a greater variety of histologic types than
      previously described. In our series, these tumors comprise 17% of all epithelial
      lacrimal gland lesions. These are the first reported cases of malignancy in this
      location. A longer follow-up period is necessary to determine the true recurrence
      rate of these tumors.

PMID- 8874434
TI  - Solitary fibrous tumor of the lacrimal gland fossa.
AB  - BACKGROUND: Solitary fibrous tumors are rare spindle cell neoplasms that most
      commonly arise in the pleura. Recently, solitary fibrous tumors of the orbital
      soft tissues have been described. The authors report the first case of solitary
      fibrous tumor arising in the lacrimal gland fossa and discuss features that may
      distinguish solitary fibrous tumor from other lacrimal fossa lesions. METHODS: A
      left lacrimal gland fossa tumor was excised via lateral orbitotomy from a 76-year
      old man and analyzed by light microscopy. Immunohistochemical studies were
      performed using antibodies to CD34, vimentin, epithelial membrane antigen,
      cytokeratins AE1-3 and Cam5.2, S-100 protein, and actin. RESULTS: The
      histopathologic features of the tumor were typical of solitary fibrous tumor. A
      well-circumscribed, variably cellular proliferation of bland spindle cells
      displayed both "patternless" and storiform growth patterns. Immunohistochemical
      studies showed that the tumor cells expressed vimentin and CD34 but did not
      express epithelial membrane antigen, cytokeratins, S-100 protein, or actin. The
      patient is free of tumor recurrence after 1 year of follow-up. CONCLUSION: The
      authors report the first case of solitary fibrous tumor arising in the lacrimal
      gland fossa. The clinical presentation of this tumor was similar to that of
      pleomorphic adenoma (benign mixed tumor) of the lacrimal gland; fortunately, the
      treatment for both of these lacrimal gland fossa neoplasms is en bloc excision.
      The histopathologic appearance of solitary fibrous tumor is varied, and
      immunohistochemical analysis may help in distinguishing solitary fibrous tumor
      from other lacrimal fossa lesions. Careful follow-up of patients with solitary
      fibrous tumor is important because recurrence may present years after excision of
      the primary tumor.

PMID- 8874435
TI  - The surgical management of lacrimal gland pseudotumors.
AB  - PURPOSE: Lacrimal gland pseudotumors belong to the group of orbital pseudotumor.
      Systemic corticosteroids are advocated as the primary treatment of choice in
      orbital pseudotumor, but recurrent and refractory cases are commonly described.
      In this retrospective study, the authors evaluate alteerative treatment options
      such as surgical excision or debulking of lacrimal gland pseudotumors. METHODS:
      The records of 26 patients referred to the Orbital Center of Amsterdam between
      1976 and 1994 with a diagnosis of lacrimal gland pseudotumor were reviewed with
      special reference to computed tomography scans, histopathologic specimens (in 23
      patients), treatment regimens, and final clinical outcome. RESULTS:
      Histopathologic review showed 15 nonsclerosing (classic) and 8 sclerosing
      lacrimal gland pseudotumors. Initial treatment consisted of corticosteroids alone
      (9/26), surgery alone (7/26), a combination of surgery and irradiation (5/26), a
      combination of surgery and corticosteroids (4/26), or indomethacin alone (1/26).
      Surgery comprised tumor excision or tumor debulking. Of the patients treated with
      corticosteroids alone, 55% (5/9) responded initially but only 22% (2/9) obtained
      a cure. However, all patients treated with surgery combined with
      corticosteroids/irradiation (9/9), with surgery alone (7/7), or with indomethacin
      alone (1/1) responded well without recurrences. The main complication of therapy
      was dry eye syndrome, the incidence being highest in patients who received
      surgery of the palpebral lobe or irradiation. The mean follow-up was 4.9 years.
      CONCLUSION: Surgical excision or debulking is a safe and effective treatment
      option in lacrimal gland pseudotumors, even in the histopathologic sclerosing
      variant.

PMID- 8874436
TI  - Site of service, anesthesia, and postoperative practice patterns for oculoplastic
      and orbital surgeries.
AB  - PURPOSE: Variations in physician practice patterns, particularly with reference
      to cost-intensive resource utilization, are increasingly being scrutinized.
      However, little information is currently available regarding physician practice
      patterns for oculoplastic surgery. METHODS: The authors surveyed members of the
      American Society of Ophthalmic Plastic and Reconstructive Surgery regarding their
      most common site of service, type of anesthesia, and first postoperative week of
      follow-up for 15 selected eyelid, lacrimal, and orbital procedures. RESULTS: The
      majority of eyelid and lacrimal surgeries are currently performed on an out
      patient basis (hospital out-patient, ambulatory surgery center, or office),
      typically using local anesthesia, with or without sedation. Regional differences
      were noted. Physicians in western states showed a greater tendency toward office
      based surgery for procedures such as blepharoplasty and ptosis repair. Orbital
      procedures were performed more frequently as a hospital inpatient surgery, under
      general anesthesia. Patterns of follow-up within the first postoperative week
      varied considerably for most procedures. Compared with admitting practices in
      1987, an obvious trend toward out-patient surgery was noted. CONCLUSION:
      Variations in practice patterns will assume greater importance as the pressure
      for cost-containment increases. Total costs are affected by physician choices for
      site of service and type of anesthesia. This study allows surgeons who perform
      oculoplastic procedures to compare their practices with a national group
      specializing in such surgery. Further outcome-oriented studies are needed to
      develop practice guidelines for "preferred patterns" of care.

PMID- 8874437
TI  - Prognostic value of morphometric features and the callender classification in
      uveal melanomas.
AB  - PURPOSE: Cytomorphometric analysis of uveal melanoma has focused on nucleolar
      characteristics, although nuclear measurements are easier and more reproducible.
      In this study, we examine a restricted set of nuclear and nucleolar
      cytomorphometric variables in the search for the most quantifiable and
      reproducible prognostic parameter among these and discover a means of assessing
      the malignancy of tumors within the different Callender subgroups. METHODS: Uveal
      melanomas from 94 patients with a minimum follow-up of 5 years underwent nuclear
      and nucleolar morphometric analysis using a digitized interactive video overlay
      system. Statistical analysis included univariate and multivariate survival
      analysis on morphometric variables and classic prognostic parameters (such as
      Callender cell type, size, etc.). RESULTS: Univariate analysis of
      cytomorphometric parameters showed the standard deviation of nuclear area (NASD)
      to be the most significant variable (P < 0.0001: Mantel-Cox, 15.2). This was
      followed by the difference between nuclear and nucleolar areas (P < 0.002; Mantel
      Cox, 9.5), the standard deviation of nucleolar area (SDNA) (P < 0.01; Mantel-Cox,
      6.4), and the standard deviation of the shortest nuclear axis (P < 0.02; Mantel
      Cox, 6.4). There was a trend for significance with the mean of the ten largest
      nucleoli (P < 0.07). Multivariate analysis of clinical and cytomorphometric
      variables showed improvement of prognostic prediction with a combination of the
      NASD, largest tumor dimension, and glaucoma (P < 0.0001; Mantel-Cox, 26.3).
      Callender cell type was strongly correlated with the NASD (P < 0.0002), the mean
      axis ratio of the nuclear area (P < 0.0007), and the mean of the ten largest
      nucleoli (P < 0.0007). CONCLUSION: Cytomorphometric analysis of uveal melanoma
      should include nuclear area and may identify tumors of differing malignancy
      within the same Callender class.

PMID- 8874438
TI  - Transpupillary thermotherapy in the management of choroidal melanoma.
AB  - BACKGROUND: Several methods of treatment have been used for choroidal melanoma.
      The purpose of this report is to evaluate the effectiveness of transpupillary
      thermotherapy using near-infrared radiation to treat choroidal melanoma. METHODS:
      A prospective study was conducted to evaluate the clinical features, treatment
      results, and complications of patients with choroidal melanoma who were treated
      with transpupillary thermotherapy delivered over one to four sessions and
      followed for at least a 6-month period. All treated tumors had either
      documentation of growth or ophthalmoscopic risk factors for future growth and/or
      metastasis. RESULTS: There were 17 patients with choroidal melanoma treated with
      transpupillary thermotherapy. The mean tumor size before treatment was 6.6 mm in
      base and 3.0 mm in thickness. The tumor margin was a mean of 2.3 mm from the
      optic disc and 2.7 mm from the foveola. Seven tumors (41%) touched the optic disc
      margin and three (18%) were under the fovea. The tumor responded to treatment in
      all patients, with a decrease in thickness and resolution of associated
      subretinal fluid. At a minimum of 6 months of follow-up, the mean tumor thickness
      was 1.7 mm, and the tumor site was a residual chorioretinal scar with partial
      visibility of the sclera in all patients. Despite the proximity to the optic disc
      and foveola, the final visual acuity was the same or improved in ten eyes (59%)
      and decreased in seven (41%). The improved vision was due to resolution of
      subfoveal fluid, whereas the decreased vision was primarily the result of
      treatment in the fovea with ultimate retinal vascular occlusion or preretinal
      traction. Although long-term follow-up is not yet available, there were no
      patients with tumor recurrence or tumor metastases. CONCLUSIONS: This preliminary
      study demonstrates that transpupillary the thermotherapy appears to be an
      effective treatment for selected small choroidal melanomas and may be a
      particularly useful modality for treating those tumors near the foveola and optic
      disc. Longer follow-up is necessary to assess for local recurrence and the impact
      of treatment on survival.

PMID- 8874439
TI  - The effect of external eye irradiation on choroidal circulation.
AB  - BACKGROUND: The effect of external beam radiation therapy (teletherapy) on the
      choroidal circulation is poorly known. Eyes irradiated with teletherapy represent
      a good model to study, without confounding factors, the pathophysiologic and
      clinical aspects of radiation-induced chorioretinal damage. This study used
      fluorescein and indocyanine green choroidal angiography to investigate the late
      effects of external eye irradiation on the choroidal circulation. METHODS:
      Fluorescein angiography and indocyanine green choroidal videoangiography were
      performed on patients with radiation retinopathy because of external eye
      irradiation for orbital and paranasal sinus malignancies. Patients were divided
      into two groups according to the treatment field (anterior unilateral or
      bilateral). RESULTS: Indocyanine green angiograms showed areas of
      choriocapillaris hypoperfusion in all eyes-unilateral or bilateral irradiation
      affected by radiation retinopathy. Late indocyanine green choroidal staining was
      found in five eyes (28%) of the patients who received unilateral anterior
      irradiation. In the same group, nine eyes (52%) had signs of choroidal
      precapillary occlusion and four eyes (23%) had rubeosis iridis without retinal
      neovascularization. One case of subfoveal choroidal neovascularization was
      documented in the bilateral irradiation group. CONCLUSIONS: Radiation side
      effects are not limited to the retinal vessels but also involve choroidal
      circulation. The damage to the choroid is primarily vascular, and its clinical
      aspects depend on the treatment fields. Anterior irradiation may be a critical
      factor for the appearance of unusual rubeosis iridis and neovascular glaucoma.

PMID- 8874440
TI  - Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study.
AB  - PURPOSE: The purpose of this study was to determine the prevalence of open-angle
      glaucoma and ocular hypertension in an Australian community whose residents are
      49 years of age or older. SUBJECTS: There were 3654 persons, representing 82.4%
      of permanent residents from an area west of Sydney, Australia, who were examined.
      The population was identified by a door-to-door census of all dwellings and by
      closely matched findings from the national census. METHODS: All participants
      received a detailed eye examination, including applanation tonometry,
      suprathreshold automated perimetry (Humphrey 76-point test), and Zeiss
      stereoscopic optic disc photography. Glaucoma suspects were asked to return for
      full threshold fields (Humphrey 30-2 test), gonioscopy, and repeat tonometry.
      RESULTS: A 5-point hemifield difference on the 76-point test was found in 616
      persons (19% of people tested). Humphrey 30-2 tests were performed on 336
      glaucoma suspects (9.2% of population), of whom 125 had typical glaucomatous
      field defects. Two hundred three persons had enlarged or asymmetric cup-disc
      ratios (> or = 0.7 in 1 or both eyes or a cup-disc ratio difference of > or =
      0.3). Open-angle glaucoma was diagnosed when glaucomatous defects on the 30-2
      test matched the optic disc changes, without regard to the intraocular pressure
      level. This congruence was found in 87 participants (2.4%), whereas an additional
      21 persons (0.6%) had clinical signs of open-angle glaucoma but incomplete
      examination findings. Open-angle glaucoma was thus found in 108 persons, a
      prevalence of 3.0% (95% confidence interval [CI], 2.5-3.6), of whom 49% were
      diagnosed previously. An exponential rise in prevalence was observed with
      increasing age. Ocular hypertension, defined as an intraocular pressure in either
      eye greater than 21 mmHg, without matching disc and field changes, was present in
      3.7% of this population (95% CI, 3.1-4.3), but there was no significant age
      related increase in prevalence. The prevalence of glaucoma was higher in women
      after adjusting for age (odds ratio, 1.5; CI, 1.0-2.2). There was no sex
      difference in the age-adjusted prevalence of ocular hypertension. CONCLUSIONS:
      These data provide detailed age and sex-specific prevalence rates for open-angle
      glaucoma and ocular hypertension in an older Australian population.

PMID- 8874441
TI  - Various glaucomatous optic nerve appearances. A color Doppler imaging study of
      retrobulbar circulation.
AB  - PURPOSE: The purpose of this study was to observe the blood flow velocity in the
      retrobulbar vessels of patients with glaucoma with different appearances of optic
      discs. METHODS: Patients with four different disc appearances (focal ischemic
      discs, myopic glaucomatous discs, senile sclerotic discs, and discs with a
      generalized enlargement of the cup) were selected from a pool of optic disc
      photographs. No clinical information from the patients was available during the
      selection. Color Doppler imaging (CDI) was performed in those patients whose
      discs clearly belonged to one of the disc patterns. The peak systolic and end
      diastolic velocity were measured and the resistance index calculated from the
      central retinal artery, short posterior ciliary arteries and ophthalmic artery.
      RESULTS: Color Doppler imaging was performed in 24 patients with focal ischemic
      discs, 26 patients with myopic glaucomatous discs, 16 patients with senile
      sclerotic discs, and 16 patients with generalized enlargements of the cup. The
      patients with senile sclerotic discs had statistically significantly lower
      diastolic velocity and a higher resistance index in their ophthalmic, central
      retinal and the mean of the short posterior ciliary arteries sampled. These
      statistical differences persisted for the ophthalmic artery even after correcting
      the values for the age differences between the groups. CONCLUSIONS: Patients with
      senile sclerotic discs seem to have greater circulatory abnormalities in their
      retrobulbar vessels studied with color Doppler imaging that are compatible with a
      higher downstream resistance in these vessels. These circulatory abnormalities
      could be related to the pathogenesis of the glaucoma in these patients.

PMID- 8874442
TI  - Quantitative studies of elastin in the optic nerve heads of persons with primary
      open-angle glaucoma.
AB  - PURPOSE: To compare quantitative and qualitative differences in elastin content
      in the optic nerve heads of glaucomatous and control human eyes. METHODS:
      Transmission electron microscopy and quantitative histomorphometry on ten control
      and ten glaucomatous eyes. RESULTS: Elastin fiber complexes in the control lamina
      cribrosa were smaller and more numerous than in the insertion zone of the sclera
      immediately surrounding the lamina. Although the density of elastin fibers in the
      normal lamina was twice that of the insertion zone (P = 0.004), the percent area
      of the connective tissue matrix occupied by elastin was the same for both zones
      (P > 0.4). There was no difference between control and glaucomatous eyes in the
      quantified parameters of elastin content or in the ultrastructure of elastin
      between control and glaucomatous eyes. CONCLUSIONS: The authors demonstrated for
      the first time that elastin in the normal lamina consists of fibers of smaller
      diameter than in the adjacent sclera, although the total amount of elastin is
      similar in both locations. This may provide maximum viscoelasticity within the
      limited connective tissue beam area of the lamina. Despite using a large number
      of specimens, the authors again found no differences between normal and
      glaucomatous eyes in the number or ultrastructural appearance of elastin fibers.

PMID- 8874443
TI  - Ocular elasticity. Is engineering stiffness a more useful characterization
      parameter than ocular rigidity?
AB  - PURPOSE: The purpose of this study is to present an analysis of the pressure
      volume relation of the eye in basic engineering terms, so as to characterize the
      deformability of the ocular shell based on its intrinsic stiffness (Young
      modulus) and morphology, as opposed to the empirical measure of ocular rigidity.
      METHODS: Starting from the structural mechanics equations describing the stress
      of spherical thin-walled vessels, the differential equation governing the eye
      pressure-volume relation is derived. This analysis, which is more rigorous than
      previously published derivations, assumes that the ocular shell has a Poisson
      ratio of 0.5. This assumption is experimentally confirmed by ultrasonic
      measurements of changes in bovine corneal thickness with intraocular pressure.
      RESULTS: Even with a number of simplifying assumptions, this basic analysis
      yields a complex result, showing that the Young modulus of the ocular shell
      material increases rapidly with distension of the eye, and is approximately
      proportional to the fourth power of the ocular shell radius. CONCLUSION: Due to
      the complexity of the phenomenon, engineering analysis does not lead to a simple
      picture of pressure-volume relation of the eye. However, it does explicitly
      separate the material properties of the ocular shell from morphologic
      contributions to pressure-volume relation of the eye. This approach allows
      pathologic changes in the pressure-volume relation of the eye to be related more
      easily to the fundamental structural mechanisms governing the nonlinear
      mechanical properties of ocular shell materials.

PMID- 8874444
TI  - Effect of a YAG laser iridotomy on intraocular pressure in pigment dispersion
      syndrome.
AB  - PURPOSE: To determine whether an iridotomy can prevent an increase in intraocular
      pressure (IOP) in patients with pigment dispersion syndrome. METHODS: Consecutive
      subjects (n = 21) recruited into this randomized, controlled clinical trial in a
      hospital-based outpatient referral center, had pigment dispersion syndrome in
      both eyes, and underwent a YAG laser iridotomy in one eye (randomly chosen); no
      intervention was performed in the fellow eye. A significant elevation of IOP was
      arbitrarily defined as an increase of more than 5 mmHg. RESULTS: Eleven (52.3%)
      untreated eyes versus 1 (4.7%) treated eye showed a significant elevation of IOP
      during the 2-year follow-up. The IOP difference between the untreated and the
      fellow treated eye at the end of the 2-year follow-up period is inversely related
      to the age of each patient. CONCLUSION: YAG laser iridotomy may reduce the
      incidence of ocular hypertension in eyes affected by pigment dispersion syndrome.
      This effect, being less pronounced after 40 years of age, may be of clinical
      relevance in young subjects.

PMID- 8874445
TI  - Autosomal-dominant anomalies of the iris pigment epithelium.
AB  - PURPOSE: The authors document two families in which anomalies of the iris pigment
      epithelium occur as an autosomal dominant trait. METHODS: Eyes of members of two
      families were examined for the presence of anomalies of the iris pigment
      epithelium. RESULTS: In both families, anomalies characterized by iris pigment
      epithelial cysts and peripupillary ruffles were observed in successive
      generations. In one family, the proband was 3 months of age, and both cysts and
      ruffles were present in affected individuals. CONCLUSIONS: Anomalies of the iris
      pigment epithelium can be inherited in an autosomal-dominant pattern. The cystic
      and ruffled phenotypes represent variable expressivity and may be evident in
      infancy.

PMID- 8874446
TI  - Remodeling filtering blebs with the neodymium:YAG laser.
AB  - PURPOSE: To describe a new method of treating large, overfiltering, leaking blebs
      using a continuous-wave neodymium:YAG laser. METHODS: Twenty-three eyes of 23
      patients underwent YAG laser remodeling because of overfiltration and hypotony
      (group 1; n = 14); leaking bleb and hypotony (group 2; n = 5); and large,
      irritating bleb (group 3; n = 4). Using a neodymium:YAG laser in the continuous
      wave multimode, a grid pattern of laser treatment was placed over the entire bleb
      using energy levels between 3.0 and 4.0 J and a laser offset between 0.9 and 1.2
      mm. A torpedo patch then was placed directly over the bleb for 48 hours. Steroid
      therapy was avoided. RESULTS: In group 1, 64% of eyes had an intraocular pressure
      increase of at least 3.0 mmHg. In group 2, 80% of bleb leaks were sealed. In
      group 3, 100% of patients had resolution of their discomfort. The elevation in
      intraocular pressure peaked at 1 to 3 months and diminished thereafter. There was
      improvement in vision of at least two Snellen acuity lines in 52% of eyes.
      Complications included the need for laser retreatment (7 eyes), creation of
      temporary bleb leak by the YAG laser (2 eyes), transient increase in intraocular
      pressure (2 eyes), and corneal edema (1 eye). CONCLUSION: The continuous-wave
      neodymium:YAG laser can be used to effectively change the appearance and behavior
      of filtering blebs, although the duration of treatment effect is unknown.

PMID- 8874447
TI  - Laser trabeculoplasty for primary open-angle glaucoma.
AB  - The purpose of the Committee on Ophthalmic Procedure Assessments is to evaluate
      on a scientific basis new and existing ophthalmic tests, devices, and procedures
      for their safety, efficacy, clinical effectiveness, and appropriate uses.
      Evaluations include examination of available literature, epidemiological analyses
      when appropriate, and compilation of opinions from recognized experts and other
      interested parties. After appropriate review by all contributors, including legal
      counsel, assessments are submitted to the Academy's Board of Trustees for
      consideration as official Academy policy.

PMID- 8874448
TI  - The NHS drops down the waiting list.

PMID- 8874449
TI  - Is site of necrosis in acute pancreatitis a predictor of outcome?

PMID- 8874450
TI  - Nerve growth factor and diabetic neuropathy.

PMID- 8874451
TI  - Insulin resistance: circumventing nature's blocks.

PMID- 8874452
TI  - Coeliac disease and autoimmunity due to unmasking of cryptic epitopes?

PMID- 8874453
TI  - Is big still beautiful in Polynesia?

PMID- 8874454
TI  - Different kind of drug-company freebie.

PMID- 8874455
TI  - Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy
      alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer
      Trial Working Party. UK Co-ordinating Committee on Cancer Research.
AB  - BACKGROUND: Non-surgical management of anal cancer by radiotherapy alone or
      combined with chemotherapy has, in uncontrolled studies, yielded similar local
      tumour control and survival rates to surgery. However, whether the addition of
      chemotherapy improves outcome without adding to morbidity is not known. Our trial
      was designed to compare combined modality therapy (CMT) with radiotherapy alone
      in patients with epidermoid anal cancer. METHODS: From 856 patients considered
      for entry to our multicentre trial, 585 patients were randomised to receive
      initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4-5
      weeks (290 patients) or the same regimen of radiotherapy combined with 5
      fluorouracil (1000 mg/m2 for 4 days or 750 mg/m2 for 5 days) by continuous
      infusion during the first and the final weeks of radiotherapy and mitomycin (12
      mg/m2) on day 1 of the first course (295 patients). We assessed clinical response
      6 weeks after initial treatment: good responders were recommended for boost
      radiotherapy and poor responders for salvage surgery. The main endpoint was local
      failure rate (> or = 6 weeks after initial treatment); secondary endpoints were
      overall and cause-specific survival. Analysis was by intention-to-treat.
      FINDINGS: In the radiotherapy and CMT arms, respectively, five and three were
      ineligible, and six and nine died 6 weeks after initial treatment. After a median
      follow-up of 42 months (interquartile range 28-62), 164 of 279 (59%) radiotherapy
      patients had a local failure compared with 101 of 283 (36%) CMT patients. This
      gave a 46% reduction in the risk of local failure in the patients receiving CMT
      (relative risk 0.54, 95% CI 0.42-0.69, p < 0.0001). The risk of death from anal
      cancer was also reduced in the CMT arm (0.71, 0.53-0.95, p = 0.02). There was no
      overall survival advantage (0.86, 0.67-1.11, p = 0.25). Early morbidity was
      significantly more frequent in the CMT arm (p = 0.03), but late morbidity
      occurred at similar rates. INTERPRETATION: Our trial shows that the standard
      treatment for most patients with epidermoid anal cancer should be a combination
      of radiotherapy and infused 5-fluorouracil and mitomycin, with surgery reserved
      for those who fall on this regimen.

PMID- 8874456
TI  - Effect of anaemia and cardiovascular disease on surgical mortality and morbidity.
AB  - BACKGROUND: Guidelines have been offered on haemoglobin thresholds for blood
      transfusion in surgical patients. However, good evidence is lacking on the
      haemoglobin concentrations at which the risk of death or serious morbidity begins
      to rise and at which transfusion is indicated. METHODS: A retrospective cohort
      study was performed in 1958 patients, 18 years and older, who underwent surgery
      and declined blood transfusion for religious reasons. The primary outcome was 30
      day mortality and the secondary outcome was 30-day mortality or in-hospital 30
      day morbidity. Cardiovascular disease was defined as a history of angina,
      myocardial infarction, congestive heart failure, or peripheral vascular disease.
      FINDINGS: The 30-day mortality was 3.2% (95% CI 2.4-4.0). The mortality was 1.3%
      (0.8-2.0) in patients with preoperative haemoglobin 12 g/dL or greater and 33.3%
      (18.6-51.0) in patients with preoperative haemoglobin less than 6 g/dL. The
      increase in risk of death associated with low preoperative haemoglobin was more
      pronounced in patients with cardiovascular disease than in patients without
      (interaction p < 0.03). The effect of blood loss on mortality was larger in
      patients with low preoperative haemoglobin than in those with a higher
      preoperative haemoglobin (interaction p < 0.001). The results were similar in
      analyses of postoperative haemoglobin and 30-day mortality or in-hospital
      morbidity. INTERPRETATION: A low preoperative haemoglobin or a substantial
      operative blood loss increases the risk of death or serious morbidity more in
      patients with cardiovascular disease than in those without. Decisions about
      transfusion should take account of cardiovascular status and operative blood loss
      as well as the haemoglobin concentration.

PMID- 8874457
TI  - Effects of maternal smoking during pregnancy and a family history of asthma on
      respiratory function in newborn infants.
AB  - INTRODUCTION: Infants of mothers who smoke have reduced respiratory function and
      are more likely to develop wheezing. Little evidence is available on the effect
      of in-utero cigarette-smoke exposure as opposed to postnatal exposure to
      environmental tobacco smoke. We used a previously validated non-invasive method
      to measure the time to peak tidal expiratory flow (tPTEF) as a proportion of
      expiratory time (tE) in newborn infants soon after birth to examine the effects
      of a family history of asthma and in-utero cigarette-smoke exposure on the
      infants' respiratory function. METHODS: We collected respiratory-function data
      from 500 healthy infants of mothers taking part in the Western Australia
      Pregnancy Cohort Study. During behaviourally defined quiet sleep, measurements
      were obtained a median of 58 h (range 26-159) after the infants were born. We
      used uncalibrated inductance plethysmography. The uncalibrated volume signal was
      differentiated to flow and used to calculate respiratory rate, total inspiratory
      time, tE, and tPTEF. Mothers answered questionnaires on demographic, medical, and
      pregnancy characteristics, including smoking history. Serum cotinine measurements
      were available to validate self-reported smoking history in a subset of mothers
      (238). RESULTS: Data suitable for analysis were obtained from 461 infants. In
      multivariate regression analysis, lower values of tPTEF/tE were independently
      associated with respiratory rate (beta coefficient per 10 breaths/min 0.018 [SE
      0.005], p < 0.01), age (beta coefficient per 10 h -0.008 [0.003], p < 0.01),
      maternal smoking during pregnancy (> 10 cigarettes daily; beta coefficient -0.049
      [0.022], p < 0.05), maternal hypertension during pregnancy (-0.037 [0.015], p <
      0.02), and a family history of asthma (-0.028[0.014], p < 0.05). CONCLUSIONS: In
      utero smoke exposure, a family history of asthma, and maternal hypertension
      during pregnancy are associated with reduced respiratory function after birth. We
      speculate that these factors adversely affect lung development in utero.

PMID- 8874458
TI  - Production of antiendomysial antibodies after in-vitro gliadin challenge of small
      intestine biopsy samples from patients with coeliac disease.
AB  - BACKGROUND: Diagnosis of many immune-mediated diseases is helped by detection of
      antibodies directed against the pathogenetic (self or foreign) antigen. In
      coeliac disease (CD), we have a situation in which antiendomysial antibodies
      (EMA), which are not specific for the pathogenetic antigen, reach a specificity
      and sensitivity of detection of CD approaching 100%, whereas detection of
      antibodies against gliadin (AGA), the pathogenetic antigen, is far less specific
      and sensitive in diagnosis. No direct evidence of a relation between
      gluten/gliadin challenge and EMA production exists. We tried to establish whether
      the small intestine of CD patients is the site of EMA production and whether
      gliadin challenge could induce their release. METHODS: Small intestine biopsy
      samples from treated (23) and untreated (16) CD patients and controls (18) were
      cultured in vitro for 24-48 h in the presence of gliadin, another alimentary
      antigen, or medium. EMA and AGA were detected in the supernatants of these organ
      culture biopsy samples by ELISA and immunofluorescence technique, respectively.
      FINDINGS: No EMA were found in the culture supernatants of biopsy samples of 18
      controls, whereas they were detected in the culture supernatants of all 16
      untreated CD patients irrespective of gliadin challenge. Conversely, EMA were not
      detected in supernatants of biopsy samples cultured in medium only from 23
      treated CD patients, but were detected in 17 of the 23 biopsy samples challenged
      with gliadin. INTERPRETATION: Our results suggest that a more complex
      pathogenetic mechanism than normally accepted is involved in CD. Furthermore, our
      findings raise the possibility that EMA, or the antigen recognised by them, are
      involved directly in the pathogenesis of CD.

PMID- 8874459
TI  - Diagnostic test for the Prader-Willi syndrome by SNRPN expression in blood.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is caused by alterations of the
      paternally derived chromosome 15 or by maternal uniparental disomy. The gene for
      the small nuclear ribonucleoprotein polypeptide N (SNRPN) is expressed only from
      the paternally derived chromosome 15, due to epigenetic imprinting. The SNRPN
      gene is not expressed in any patients with PWS regardless of the underlying
      cytogenetic or molecular causes. METHODS: To develop a rapid molecular diagnostic
      assay for PWS, we tested the expression of the SNRPN gene and a control gene in 9
      patients with PWS and 40 control individuals by PCR analysis of reverse
      transcribed mRNA from blood leucocytes. We then tested 11 blood samples from
      patients with suspected PWS. FINDINGS: SNRPN expression could readily be detected
      in blood leucocytes by PCR analysis in all control samples but not in samples
      from known PWS patients. Four suspected plus were negative for SNRPN expression
      were found to have chromosome 15 rearrangements, while the diagnosis of PWS was
      excluded in the remaining seven with normal SNRPN expression based on clinical,
      molecular, and cytogenetic findings. INTERPRETATION: The SNRPN-expression test is
      rapid and reliable in the molecular diagnosis of Prader-Willi syndrome.

PMID- 8874460
TI  - A soldier who had seizures after drinking quarter of a litre of wine.

PMID- 8874461
TI  - Prevention of HIV infection in developing countries.
AB  - The HIV/AIDS epidemic continues to spread rapidly in developing countries.
      Heterosexual transmission accounts for almost three-quarters of infections.
      Current strategies have been effective in the prevention of HIV spread within
      certain groups but they have had limited impact on the general spread of the
      epidemic. There is a need to complement these strategies with approaches that
      will influence the social and environmental determinants of risk to enable those
      vulnerable to infection to protect themselves.

PMID- 8874462
TI  - The rise of Western medicine in India.

PMID- 8874463
TI  - Statins do more than just lower cholesterol.

PMID- 8874464
TI  - Tracing patients in rural Africa.

PMID- 8874465
TI  - Japanese hospital list starts worry about HIV.

PMID- 8874466
TI  - Oral contraceptives and mortality from venous thromboembolism.

PMID- 8874467
TI  - Oral contraceptives and mortality from venous thromboembolism.

PMID- 8874468
TI  - Oral contraceptives and mortality from venous thromboembolism.

PMID- 8874469
TI  - Coordination of poliomyelitis immunisation programme in China's border areas.

PMID- 8874470
TI  - Intraductal component and BRCA1-associated breast cancer.

PMID- 8874471
TI  - Tetanus toxoid and spontaneous abortions: is there epidemiological evidence of an
      association?

PMID- 8874472
TI  - Effects of dopamine and adrenaline infusions in severe infection.

PMID- 8874473
TI  - Effects of dopamine and adrenaline infusions in severe infection.

PMID- 8874474
TI  - Ifosfamide nephrotoxicity: deleterious effect of previous cisplatin
      administration.

PMID- 8874475
TI  - Circulating vascular permeability factor/vascular endothelial growth factor in
      erythroderma.

PMID- 8874476
TI  - Hospice care for children.

PMID- 8874477
TI  - Dysgeusia ("cognate, dis-gusting")

PMID- 8874478
TI  - Public pretences about euthanasia in Japan.

PMID- 8874479
TI  - Culture and the antenatal first visit.

PMID- 8874480
TI  - Community-sampling of blood in suspected meningococcal infection.

PMID- 8874481
TI  - Stress-related growth failure.

PMID- 8874482
TI  - Steroid-free immunosuppression in renal transplantation.

PMID- 8874483
TI  - No detectable mutations at Werner helicase locus in progeria.

PMID- 8874484
TI  - Concentration of etretinate in plasma and subcutaneous fat after long-term
      acitretin.

PMID- 8874485
TI  - Rapidly progressive infection and Kaposi's sarcoma in patient with a novel
      syncytium-inducing HIV-B variant.

PMID- 8874486
TI  - Complications of oral anticoagulant treatment.

PMID- 8874487
TI  - Complications of oral anticoagulant treatment.

PMID- 8874488
TI  - UK academy of medicine.

PMID- 8874489
TI  - Cytokine regulation of the macrophage (M phi) system studied using the colony
      stimulating factor-1-deficient op/op mouse.
AB  - The macrophage (M phi) lineage is more complex than other myeloid lineages of
      hematopoietic cells and includes strikingly different end cells such as Kupffer
      cells, alveolar M phi, histiocytes, serosal M phi, synovial type A cells,
      microglia, osteoclasts, and possibly dendritic cells. These cells are formed
      under the influence of primary M phi growth factors such as colony stimulating
      factor (CSF)-1, granulocyte-M phi (GM)-CSF, and interleukin-3. The dissection of
      the system has been greatly facilitated by discovery of the osteopetrotic op/op
      mouse, which has a spontaneous knockout of the gene for CSF-1 and possesses
      generalized but differential deficiency of various local subpopulations of M phi.
      Studies using this model indicate that the M phi lineage is split into CSF-1
      dependent and CSF-1-independent cells that are largely independently regulated.
      These contribute variably to different local populations and have largely, but
      not totally, overlapping functions. Both CSF-1 and GM-CSF are responsible for
      transition of cells of the M phi lineage from bone marrow to blood, and from
      blood to tissues, and have a critical extramedullary role. Regulation of the M
      phi system by CSF-1 is complex, with some local populations dependent on
      circulating CSF-1 and some supported exclusively by locally produced CSF-1.
      Colony stimulating factor-1-dependent M phi are not required for the generation
      of a specific immune response. Instead, most likely they play a regulatory role
      in various tissue reactions including responses to bacterial infection,
      neoplasia, and atherosclerosis. A hypothetical major role of CSF-1-independent M
      phi is to collaborate with lymphocytes in mounting an immune response. These
      issues need further exploration using animals with knockouts of genes for other M
      phi growth and activation factors and their receptors.

PMID- 8874490
TI  - Endocytosis, intracellular transport, and cytotoxic action of Shiga toxin and
      ricin.
AB  - Protein toxins such as ricin and Shiga toxin with intracellular targets have to
      be endocytosed and translocated to the cytosol to inhibit the protein synthesis
      and thereby kill the cell. Ricin is internalized by both clathrin-dependent and 
      independent endocytic mechanisms, whereas Shiga toxin seems to be taken up
      exclusively from clathrin-coated pits. After endocytosis, internalized membrane
      and content are delivered to endosomes, where sorting for further routing in the
      cell takes place. Toxins that remain membrane bound at low endosomal pH can be
      recycled to the cell surface or transcytosed in polarized epithelia. A large
      proportion of internalized toxin is transported to lysosomes for degradation.
      Most importantly, a fraction of the internalized ricin and Shiga toxin molecules
      is delivered to the trans-Golgi network (TGN). Shiga toxin can, in some very
      sensitive cells, be transported retrogradely through the Golgi cisterns all the
      way back to the endoplasmic reticulum (ER), and it is possible that also ricin is
      transported retrogradely to the ER. In this review, a cell biological overview of
      these intracellular transport steps is presented, and evidence is provided that
      the delivery to the TGN and the subsequent retrograde transport to the ER are
      required for optimal intoxication. Moreover, it is argued that knowledge of this
      transport is important for targeted drug delivery such as the application of
      immunotoxins in cancer therapy.

PMID- 8874491
TI  - Mechanisms of smooth muscle contraction.
AB  - Work performed with differentiated contractile smooth muscle tissue over the last
      two decades has made clear that covalent modification of myosin by
      phosphorylation of the 20-kDa myosin light chains is a significant mode of
      regulation of contractile activity in smooth muscle, particularly in regard to
      the generation of phasic contractions and the initial development of tonic
      contractions. This regulatory mechanism appears to be of unique importance in
      smooth muscle compared with striated muscle. It is equally clear, however, that
      there is an important role for protein kinase C in the regulation of smooth
      muscle tone maintenance, particularly in vascular smooth muscle. Several possible
      signal transduction cascades involving protein kinase C are outlined. Increasing
      evidence suggests a link between protein kinase C and actin-based regulatory
      mechanisms. This review places emphasis on relating up-to-date biochemical facts
      to the physiological realities of the smooth muscle cell.

PMID- 8874492
TI  - Growth, differentiation, and survival: multiple physiological functions for
      insulin-like growth factors.
AB  - The insulin-like growth factors (IGFs), IGF-I and IGF-II, comprise a conserved
      pair of secreted proteins with diverse effects on growth, development, and
      metabolism. Insulin-like growth factor action is initiated upon binding to cell
      surface receptors and is modulated through interactions with secreted IGF binding
      proteins (IGFBPs). The last decade has seen an explosion of new information about
      the physiological roles of the IGFs. In this review, we critically examine this
      information from biochemical, cell biological, and molecular genetic
      perspectives. We discuss the structures and functions of the two IGF receptors,
      outline the actions of the six IGFBPs, and summarize and interpret recent studies
      highlighting essential roles for components of the IGF system in the growth and
      development of the embryo and fetus, in tissue differentiation, in cell survival
      and proliferation, and in cancer. These results are discussed in the context of
      new opportunities for understanding the mechanisms of IGF action in multiple
      biological processes.

PMID- 8874493
TI  - Ryanodine receptor Ca2+ release channels: does diversity in form equal diversity
      in function?
AB  - Complexities in calcium signaling in eukaryotic cells require diversity in the
      proteins involved in generating these signals. In this review, we consider the
      ryanodine receptor (RyR) family of intracellular calcium release channels. This
      includes species, tissue, and cellular distributions of the RyRs and mechanisms
      of activation, deactivation, and inactivation of RyR calcium release events. In
      addition, as first observed in nonmammalian vertebrate skeletal muscles, it is
      now clear that more than one RyR isoform is frequently coexpressed within many
      cell types. How multiple ryanodine receptor release channels are used to generate
      intracellular calcium transients is unknown. Therefore, a primary focus of this
      review is why more than one RyR is required for this purpose, particularly in a
      tissue, such as vertebrate fast-twitch skeletal muscles, where a relatively
      simple and straightforward change in calcium would appear to be required to
      elicit contraction. Finally, the roles of the RyR isoforms and the calcium
      release events they mediate in the development of embryonic skeletal muscle are
      considered.

PMID- 8874494
TI  - Structure and functional mechanism of porins.
AB  - Cellular organisms such as gram-negative bacteria are enclosed by a dual lipid
      bilayer system. The outer membranes of the dual bilayer envelopes predominantly
      contain large numbers of water-filled transmembrane protein channels known as
      porins. The recent availability of the molecular structures of several bacterial
      porins has provided the opportunity for comparing the results of a wide range of
      functional studies with the atomic level structural details of these membrane
      channels. Taken together, the structure and function data present the most
      comprehensive set of boundary conditions available for the evaluation of theory
      and models predicting the characteristics of solute transport through membrane
      protein channels. In this paper, we review the high-resolution structure data
      from the bacterial porins, as well as recent theoretical studies, in the context
      of biophysical and biochemical observations and discuss the molecular mechanisms
      responsible for the transport of solutes through porin channels. Particular
      emphasis has been placed on the features and roles of common structural elements,
      channel sterics and electrostatics, and voltage-dependent gating. A model for
      water-coordinated transport, providing a qualitative view of the porin transport
      mechanism, is also described.

PMID- 8874495
TI  - Mechanism of signaling by growth hormone receptor.
AB  - Growth hormone (GH) has long been known to stimulate linear growth and regulate
      metabolism. The cellular mechanism by which GH elicits these effects has only
      recently begun to be understood. This review provides an overview of a current
      model of GH signaling. Briefly, binding of GH to GH receptor induces receptor
      dimerization and activation of the tyrosine kinase JAK2. Tyrosyl phosphorylation
      of GH receptor and JAK2 recruits and activates signaling molecules such as Stat
      transcription factors, SHC, and insulin receptor substrates 1 and 2 that lead to
      the release of second messengers such as diacylglycerol, calcium, and nitric
      oxide and the activation of enzymes such as mitogen-activated protein kinase,
      protein kinase C, phospholipase A2, and phosphatidylinositol 3'-kinase. These
      pathways regulate cellular function including gene transcription, metabolite
      transport, and enzymatic activity that result in the ability of GH to control
      body growth and metabolism.

PMID- 8874496
TI  - Regulation of gene expression by insulin.
AB  - While insulin has long been known to modulate intracellular metabolism by
      altering the activity or intracellular location of various enzymes, it is only in
      the past 10 years that the regulation of gene expression by insulin has been
      recognized as a major action of this hormone. This review principally focuses on
      the regulation of gene transcription by insulin, although recent progress in the
      understanding of insulin-regulated mRNA stability and translation is also
      summarized. The identification of cis-acting elements and associated trans-acting
      factors through which insulin either increases or decreases the transcription of
      specific genes is reviewed in detail. Recent advances in the understanding of the
      mechanisms of insulin signaling are discussed in the context of insulin-regulated
      gene transcription, and emphasis is placed on the gaps that remain between the
      upstream signaling molecules and the downstream trans-acting factors whose
      binding/transactivation potential is ultimately regulated. Finally, potential
      gene expression defects that may contribute to the pathophysiology of non-insulin
      dependent diabetes mellitus and hypertriglyceridemia are considered.

PMID- 8874497
TI  - Adenovirus serotype evolution is driven by illegitimate recombination in the
      hypervariable regions of the hexon protein.
AB  - The origin of AIDS-associated adenoviruses (AV 43-AV 49) was investigated by
      examining evolutionary relationships among 18 serologically related subgenus D
      serotypes and 3 intermediates and determining the mutation rate of a single
      serotype, AV 48, among clinical isolates from AIDS patients over a 6-year period.
      Nucleotide sequence of conserved and seven hypervariable regions (HVRs) of the
      hexon protein, the pVI core protein signal peptide, and noncoding region between
      the two genes was determined. Among AV 48 isolates the base misincorporation rate
      was 3.2 per 10,000 bases over 6 years. A 6-bp deletion occurred in one isolate
      between short direct repeats in HVR 7. Among subgenus D serotypes mutation rates
      were extremely low in the pVI peptide, the 5' hexon noncoding region, and first
      187 bases of hexon protein. Small 2- and 3-bp deletions between short direct
      repeats in a polypurine stretch in the noncoding region occurred in 3 strains.
      Mutation increased with proximity to the HVRs. Within HVR 1, 2, 4, 5, and 7
      variability consisted of extensive intrachromosomal illegitimate recombination,
      including deletions between short direct repeats, insertions and duplications in
      repetitive polypurine stretches, and numerous base substitutions. All serotypes
      and intermediates differed by at least one illegitimate recombination event, with
      one exception. We conclude that AV serotype evolution is driven by illegitimate
      recombination events (antigenic shift), concommitant with single base mutation
      (antigenic drift), and that the HVRs are "hot spots" for both. These events could
      be explained by slippage-misalignment of the AV DNA polymerase in repetitive
      polypurine stretches during single-strand DNA replication. This mutability in the
      surface regions of the major viral coat protein confers a distinct survival
      advantage to this family of viruses.

PMID- 8874498
TI  - Nla and Nlb of peanut stripe potyvirus are present in the nucleus of infected
      cells, but do not form inclusions.
AB  - We investigated, by immunological and gene-fusion methods, whether the failure of
      peanut stripe potyvirus (PStV)-encoded nuclear inclusion proteins a (Nla) and b
      (Nlb) to form nuclear inclusions is due to the lack of their in vivo accumulation
      or the inability of one or both proteins to be transported into the nucleus Nla
      domains (Nla-VPg and Nla-proteinase), full-length Nlb, and full-length
      cylindrical inclusion (CI) protein of PStV were cloned, expressed in Escherichia
      coli, and used for antisera production. Immunoblot analysis of accumulation of
      Nla, Nlb, and CI in time course experiments revealed that they accumulated to
      similar levels in PStV-infected Nicotiana benthamiana. In immunocytochemical
      studies with electron microscopy, antiserum against Nla-VPg, Nla-Pro, and Nlb
      specifically labeled Nla and Nlb proteins throughout the nuclei of PStV-infected
      cells, in the absence of nuclear inclusions. Translational fusions were made
      between Nla and Nlb to either the green fluorescence protein or the beta
      glucuronidase in vectors for transient gene expression or stable expression in
      transgenic plants respectively. Fusion proteins containing Nla accumulated in the
      nucleus, whereas fusion proteins containing Nlb accumulated in a punctate pattern
      in the cytoplasm. These data indicate that at least Nla possesses a nuclear
      localization signal.

PMID- 8874499
TI  - Intracellular localization of the herpes simplex virus type-1 origin binding
      protein, UL9.
AB  - UL9 is the origin binding protein of herpes simplex virus type-1 (HSV-1). A UL9
      specific monoclonal antibody (17B) whose epitope maps to the N-terminal 33 amino
      acids was used to study the localization of UL9 in infected and transfected
      cells. We demonstrate the colocalization of UL9 and the HSV-1 single-strand DNA
      binding protein (ICP8 or UL29) in replication compartments, sites of viral DNA
      synthesis. On the other hand, UL9 does not completely colocalize with ICP8 in
      prereplicative sites, structures observed under conditions that inhibit viral DNA
      polymerase. Cells transfected with various deletion or pyruvate kinase fusion
      constructs were analyzed by indirect immunofluorescence assay to define the
      nuclear localization signal (NLS) of UL9. Deletion analysis showed that the
      region required for nuclear localization lies within the C-terminal DNA binding
      domian (amino acids 535-851). Various regions of UL9 were tested in fusion
      constructs for their ability to direct the normally cytoplasmic chicken pyruvate
      kinase protein to the nucleus. A fusion construct containing the carboxy-terminal
      107 residues (amino acids 745-851) localized efficiently to the nucleus, whereas
      a fusion construct containing the N-terminal 660 amino acids of UL9 was unable to
      do so. Mutations designed to alter a potential NLS sequence (793-KREFAGARFKLR
      804) within the C-terminal 107 residues result in a mutant UL9 protein which
      falls to localize efficiently to the nucleus. These results suggest that the
      major NLS of UL9 maps within the C-terminal 107 amino acids.

PMID- 8874500
TI  - The role of AV2 ("precoat") and coat protein in viral replication and movement in
      tomato leaf curl geminivirus.
AB  - We analyzed various mutants of tomato leaf curl virus-India to investigate the
      role of ORFs AV3, AV2, and coat protein (CP) in viral replication, movement, and
      symptom development. The results of these studies indicate that ORF AV3 does not
      encode a protein. Plants inoculated with infectious DNA which contained deletions
      in AV2 developed very mild symptoms and accumulated only low levels of both
      single-stranded (ss) and double-stranded (ds) viral DNA, whereas inoculated
      protoplasts accumulated both ss and dsDNA to wild-type levels, showing that AV2
      is required for efficient viral movement. However, both plants and protoplasts
      inoculated with substitution, frameshift, and other similar mutations in AV2
      accumulated low levels of viral DNA. The low levels of accumulation of DNA of
      these mutants were apparently not due to a defect in AV2 synthesis. Mutations in
      the CP caused a marked decrease in ssDNA accumulation in plants and protoplasts
      while increasing dsDNA accumulation in protoplasts. Mutations in both AV2 and CP
      behaved like AV2 mutants in plants and like CP mutants in protoplasts. The
      results demonstrated that multiple functions provided by AV2, BV1, BC1 are
      essential for viral movement, and that changes in A-component virion-sense mRNA
      structure or translation affect viral replication.

PMID- 8874501
TI  - Partial characterization of a Sendai virus replication promoter and the rule of
      six.
AB  - We have used a cDNA copy of a natural, internally deleted, Sendai virus defective
      interfering genome to study the effect of insertions and deletions (which
      maintain the hexamer genome length) on the ability of viral genomes to be
      amplified in a transfected cell system. The insertion of 18 nt at nt72 (In the 5'
      untranslated region of the N gene, just downstream of the le+ region) was found
      to be lethal, whereas similar insertions further from the genome ends were well
      tolerated. Curiously, the insertion of 6 nt on either side of the le+/N junction
      (at nt47 and nt87) was well tolerated, but the insertion of 12 nt at either site,
      or of 6 nt at both sites, largely ablated genome amplification. These results
      suggest that an element of this replication promoter is located downstream of
      nt87, in the 5' untranslated region of the first gene. Remarkably, the addition
      of 6 nt by the insertion of 2, 3, or 4 nt at nt47 plus the insertion of 4, 3, or
      2 nt, respectively, at nt87 was poorly tolerated, presumably because the hexamer
      phase of the intervening sequence was altered with respect to the N subunits of
      the template. These results suggest that the rule of six operates, at least in
      part, at the level of the initiation of antigenome synthesis.

PMID- 8874502
TI  - The V3 domain of SIVmac251 gp120 contains a linear neutralizing epitope.
AB  - Antisera to 21 synthetic peptides containing hydrophilic sequences of simian
      immunodeficiency virus strain mac251 (SIVmac251) gp120 and gp32 were tested for
      the ability to neutralize SIVmac251. Goat antisera raised to peptides SP-1 and SP
      1V containing the carboxy-terminal portion of the V3 domain of SIVmac251 gp120
      between amino acids 327 and 339 inhibited syncytium formation (90% inhibition at
      a 1/1024 dilution) and cell killing of CEMx174 cells by SIVmac251 (50%)
      inhibition of cell killing at a dilution of 1/5832), SIVDeltaB670 (1/568), and
      SIVsmH4 (1/740). Neutralizing antibodies to SIVmac251, SIVDeltaB670, and SIVsmH4
      could be adsorbed by peptides containing a neutralizing V3 sequence of SIVmac251
      gp120 (GLVFHSQPIND, amino acids 329-339) but not by peptides lacking this
      sequence. This V3 neutralizing region corresponds to a homologous V3 neutralizing
      site within HIV-2 gp120 reported by Bjorling et al. 1991, Proc. Natl. Acad. Sci.
      USA 88, 6082-6086, 1994, J. Immunol. 152, 1952-1959). Antibodies in 20 of 31 sera
      obtained from rhesus macaques infected with SIVmac251 reacted with a peptide
      containing the entire V3 sequence of SIVmac251 gp120, whereas no sera contained
      antibodies reacting with the V3 neutralizing site between amino acids 329 and
      339. Low levels of antibody-mediated recognition and subsequent lack of selective
      pressure against this linear V3 neutralizing site might in part explain why this
      region is not a dominant neutralizing site and also why sequences within V3 do
      not vary during the course of SIV infection.

PMID- 8874503
TI  - The Amsacta moorei entomopoxvirus spheroidin gene is improperly transcribed in
      vertebrate poxviruses.
AB  - The Amsacta moorei entomopoxvirus (AmEPv) spheroidin is the most highly expressed
      late viral gene product in infected insect cells. However, when a cassette
      containing the spheroidin gene and putative promoter was inserted into cowpox
      (CPV) or vaccinia viruses, only very low levels of spheroldin gene expression
      were observed. Primer extension analysis suggests much lower spheroidin gene
      transcript levels than seen either for the highly expressed CPV A-type inclusion
      gene or for the spheroidin gene within infected insect cells, indicating that in
      vertebrate cells, the spheroidin promoter functions poorly if at all. Examination
      of the spheroidin mRNA synthesized in recombinant CPV shows that the 5' start
      site of the spheroidin transcript was also unexpectedly imprecise and upstream
      (approximately 31 bp) of the well-defined start site normally observed in AmEPV
      infected insect cells. Sequencing of the 5' terminus of the CPV recombinant
      spheroidin mRNA suggested that 5' poly(A), a characteristic feature of late
      poxvirus mRNAs and spheroidin mRNA derived from insect cells, was absent, despite
      the presence of the typical vertebrate poxvirus late promoter consensus sequence,
      TAAATG. Our results indicate that insect and vertebrate poxvirus promoters may
      not be universally interchangeable and imply that there are regulatory features
      of gene expression unique to the infected insect cell environment.

PMID- 8874504
TI  - Mutational analysis of a neutralization epitope on the dengue type 2 virus (DEN2)
      envelope protein: monoclonal antibody resistant DEN2/DEN4 chimeras exhibit
      reduced mouse neurovirulence.
AB  - The antigenic site of dengue type 2 virus (DEN2)-neutralizing monoclonal antibody
      (mab) 3H5 was investigated by mutational analysis. Sequence comparisons indicated
      that much of the 12-amino-acid sequence extending from position 386 to 397 of the
      DEN2 envelope glycoprotein (E) previously thought to represent the DEN2-specific
      mab 3H5 binding site was also present in some dengue type 1, 3, or 4 virus
      strains. However, the region occupied by the Glu-Pro-Gly sequence at upstream
      positions 383 to 385 was completely conserved among DEN2 strains, but divergent
      in other serotype viruses, suggesting that this sequence might be part of the
      antigenic site of mab 3H5. We investigated this possibility by employing the
      previously constructed chimeric DEN2(PreM-E)/DEN4 cDNA clone to produce viable
      mutants bearing DEN2 PreM and E sequences that could be analyzed for binding to
      and neutralization by mab 3H5. We constructed 13 such DEN2 mutants that contained
      a single amino acid substitution in the region between positions 383 and 393 of
      DEN2 E. Each single substitution in the region spanning positions 386 through 393
      of DEN2 yielded a virus that was as reactive with mab 3H5 as the parental
      chimeric virus. These results are consistent with the extent of sequence
      conservation in the region. In contrast, 5 of 6 mutants that sustained an amino
      acid substitution at position 383, 384, or 385 failed to react with mab 3H5 as
      detected by immunofluorescence assay and failed to be neutralized by the mab.
      Interestingly, each of the 5 mab-resistant DEN2 mutants also exhibited reduced
      mouse neurovirulence compared to parental chimeric DEN2 when inoculated
      intracerebrally. These observations suggest that the Glu-Pro-Gly sequence at
      positions 383-386 of the DEN2 E is a component of the site against which mab 3H5
      is directed. In the recently determined three-dimensional structure of the
      related tick-borne encephalitis virus E, the Glu-Pro-Gly sequence would be
      located on the lateral surface of the immunoglobulin-like domain that is proposed
      to bind to the host cell receptor.

PMID- 8874505
TI  - Sequence analysis of normal and rearranged NSP5 genes from human rotavirus
      strains isolated in nature: implications for the occurrence of the rearrangement
      at the step of plus strand synthesis.
AB  - We determined the nucleotide sequences of normal and rearranged NSP5 genes from
      the human rotavirus strains (Mc323 and Mc345, respectively) which had previously
      been isolated from Thai infants with diarrhea in the same epidemic season. While
      the two strains shared G serotype 9 specificity and subgroup I specificity and
      they showed a high level of overall genomic relatedness to each other, they
      exhibited different RNA profiles; a long pattern for Mc323 and a super-short
      pattern for Mc345. Their NSP5 sequences were more closely related to those of
      porcine rotaviruses than to those of human rotaviruses. Mc345 NSP5 gene was shown
      to have concatemerization. In a head-to-tail orientation resulting in its length
      being 1182 bp, as compared with the Mc323 NSP5 sequence which was 664 bp in
      length. Sequence analysis suggested that the rearrangement found in the strain
      Mc345 occurred at the step of plus strand synthesis.

PMID- 8874506
TI  - Avian reovirus-induced syncytium formation is independent of infectious progeny
      virus production and enhances the rate, but is not essential, for virus-induced
      cytopathology and virus egress.
AB  - The nonenveloped avian reoviruses represent a distinct antigenic subgroup of
      orthoreoviruses. Unlike their mammalian counterparts, the avian reoviruses
      exhibit the unusual property of inducing rapid and extensive syncytium formation
      in cell cultures, a cytopathic effect more commonly associated with enveloped
      virus replication. While the syncytium-inducing capability of avian reovirus has
      been known for quite some time, the relationship between cell fusion and the
      virus replication cycle has not been determined. The conservation of the
      syncytial phenotype among all field isolates of avian reovirus suggests that
      avian reovirus-induced syncytium formation either reflects an essential step in
      the virus replication cycle involving intracellular membrane interactions or that
      cell fusion contributes to enhanced virus replication in infected animals. In
      order to distinguish between these possibilities, we have examined several
      aspects of virus replication in the presence of inhibitors of syncytium
      formation. Inhibitors of intracellular vesicle transport and O-linked
      glycosylation eliminated or markedly reduced syncytium formation with little
      effect on the rate or extent of virus macromolecular synthesis and infectious
      progeny virus production. Moreover, syncytium formation was not required for
      virus-induced cytopathology or virus egress but did significantly enhance the
      rate of both of these processes. The data indicate that, unlike the syncytium
      inducing enveloped viruses, the membrane interactions and protein trafficking
      required for avian reovirus-induced syncytium formation do not reflect the
      sequelae of an essential step in the virus replication cycle. These results
      suggest that the conservation of the avian reovirus syncytial phenotype may
      reflect a fortuitous aspect of virus replication which confers advantages
      associated with the rapid spread of the virus within an infected host.

PMID- 8874507
TI  - Role of cotranslational disulfide bond formation in the folding of the
      hemagglutinin-neuraminidase protein of Newcastle disease virus.
AB  - The role of cotranslational disulfide bond formation in the folding pathway of
      the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus was
      explored. Electrophoresis of pulse-labeled HN protein in the presence or absence
      of reducing agent showed that, characteristic of many glycoproteins, the nascent
      HN protein contains intramolecular disulfide bonds. As reported by Braakman et
      al. (EMBO J. 11, 1717-1722, 1992), incubation of cells in dithiothreitol (DTT)
      blocked the formation of these bonds. Removal of DTT after a pulse-label allowed
      for the subsequent formation of intramolecular disulfide bonds and folding of the
      molecule as assayed by the appearance of conformationally sensitive antigenic
      sites and by the formation of disulfide-linked dimers. However, the t1/2 for the
      formation of a conformationally sensitive antigenic site after synthesis in the
      presence of DTT was over twice that of the control. Furthermore, the order of
      appearance of the antigenic sites was different from the control, suggesting that
      inhibition of cotranslational disulfide bond formation altered the folding
      pathway of the protein. Similar results were obtained in a cell-free system
      containing membranes. The HN protein forced to form intramolecular disulfide
      bonds posttranslationally had no detectable neuraminidase or cell attachment
      activity, suggesting that the protein had an abnormal conformation.

PMID- 8874508
TI  - Monoclonal antibodies to HPV-6 L1 virus-like particles identify conformational
      and linear neutralizing epitopes on HPV-11 in addition to type-specific epitopes
      on HPV-6.
AB  - A set of 13 monoclonal antibodies (MAbs) was generated against HPV-6 L1 virus
      like particles (VLPs), screened for reactivity to HPV-6 and HPV-11 L1 VLPs by
      ELISA, and tested for neutralization of HPV-11 infection. Both cross-reactive and
      type-specific epitopes were detected such that 4 of 13 MAbs reacted to surface
      conformational sites on HPV-6 L1 VLPs and the remaining 9 MAbs were cross
      reactive to both HPV-6 and HPV-11 L1 VLPs. four of the 9 cross-reactive MAbs were
      able to neutralize HPV-11 infectivity, and 3 of 4 of these neutralizing MAbs (N
      MAbs) identified shared surface conformational sites. One N-MAb therefore
      recognized a surface linear epitope as judged by positive binding to L1 in a
      Western blot assay. The neutralization status of these cross-reactive MAbs with
      regard to HPV-6 could not be assayed. These results demonstrated that the closely
      related HPV types 6 and 11 contain both type-specific and shared neutralizing
      epitopes.

PMID- 8874509
TI  - Effects of the estrous cycle on local humoral immune responses and protection of
      intranasally immunized female mice against herpes simplex virus type 2 infection
      in the genital tract.
AB  - This study demonstrates that the levels of gB-specific IgG and IgA in vaginal
      washes of mice immunized intranasally (i.n.) with a recombinant adenovirus vector
      expressing herpes simplex virus (HSV) glycoprotein B (AdgB8) vary inversely with
      each other and are dependent on the stage of the estrous cycle. Anti-gB IgA
      titers in vaginal washes were significantly higher during estrus than diestrus or
      proestrus, whereas specific IgG titers were significantly higher during diestrus
      than estrus. This was further demonstrated in hormone-treated mice, where
      progesterone administration induced a diestrus-like state that resulted in
      elevated specific IgG-to-IgA ratios. Interestingly, unimmunized mice were only
      susceptible to intravaginal (ivag) infection with HSV-2 during diestrus. Mice
      immunized i.n. with AdgB8 and given progesterone were protected from a lethal
      intravaginal HSV-2 challenge, despite the fact that virus replication was present
      for 4 days postchallenge. Further, high numbers of gB-specific IgA and IgG
      antibody-secreting cells were present in both the genital tracts and the draining
      iliac lymph nodes of i.n.-immunized, but not unimmunized, mice 6 days following
      ivag HSV-2 challenge. These results demonstrate that the levels of specific
      antibodies in the female genital tract are dependent on the stage of the estrous
      cycle. Furthermore, i.n. AdgB8 immunization provided a significant level of
      protection and specific IgA and IgG antibody-secreting cells in the genital
      tissues during resolution of an ivag infection with HSV-2.

PMID- 8874510
TI  - Reciprocal effects of splicing and polyadenylation on human immunodeficiency
      virus type 1 pre-mRNA processing.
AB  - Insertion of a functional splicing cassette into a construct containing the HIV-1
      poly(A) site followed by the adenovirus L3 poly(A) site results in both specific
      stimulation of 3' end processing at the HIV-1 site and an increase in the steady
      state levels of RNA processed at both sites. To further evaluate this influence
      of splicing on processing of the HIV-1 poly(A) site, defined mutations which
      alter or abolish splicing of the intron were made and analyzed for their effects
      on polyadenylation and steady-state levels of RNA. The data show that a point
      mutation at the 3' splice site caused activation of a cryptic splice acceptor
      that is as efficient as the wild-type acceptor. Substitution of this mutant
      intron for the wild-type intron resulted in stimulation of the HIV-1 poly(A) site
      to levels equivalent to those caused by the wild-type intron. This mutant did
      not, however, have as great an effect on steady-state RNA levels as the wild-type
      intron. A second construct containing a mutated branch point and polypyrimidine
      tract resulted in abolishment of splicing and a decrease in both poly(A) site use
      and steady-state levels of RNA. These data demonstrate that the enhanced use of
      the HIV-1 poly(A) site is a direct result of the splicing reaction, and not
      merely due to the sequences that were inserted. The effect that poly(A) site
      strength has on splicing was also addressed. Using activation of the cryptic
      splice acceptor to indicate changes in splicing efficiency resulting from
      alterations in poly(A) site strength, it was determined that poly(A) site
      strength does have an effect on the efficiency of the splicing reaction.

PMID- 8874511
TI  - New stimulation ligand of the adenovirus 2 protease.
AB  - The catalytic activity of the adenovirus cysteine peptidase is increased by a
      specific 11-amino-acid peptide adduct (GVQSLKRRRCF, referred to as pVIc). To
      identify additional peptides which might bind and alter the activity of the
      protease, a cysteine-constrained random peptide phage library was screened. Of 29
      different phages which were isolated, 7 contained the consensus sequence VEGGS.
      Despite a superficial similarity to the substrate cleavage site of the protease,
      the peptide was not digested by the enzyme. VEGGS and pVIc altered protease
      activity similarly without sharing sequence similarity. To similar degrees, pVIc
      and VEGGS (a) stimulated the activity of the recombinant protease, (b) had no
      effect on viral protease, (c) increased the fluorescence emission of tryptophan
      residues in the protease, suggesting a conformational change, and (d) inhibited
      wt virus infection, but rescued ts1 infection at the nonpermissive temperature.
      The experiments also suggest that once the protease has been stimulated by one
      peptide, the other peptide has no further activity on the recombinant adenovirus
      cysteine protease, suggesting that the two peptides bring about the same change
      on the protease via different binding sites.

PMID- 8874512
TI  - Role of Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) in
      the propagation of MPMV vectors by genetic complementation using
      homologous/heterologous env genes.
AB  - To study Mason-Pfizer monkey virus (MPMV) replication over a single round, virus
      particles were generated that contain a replication-defective vector encoding a
      dominant selectable marker, the hygromycin B phosphotransferase (hyg) gene.
      Genetic complementation with a homologous MPMV envelope glycoprotein (Env-gp) or
      pseudotyping by several heterologous Env-gps from a variety of viruses resulted
      in infectious MPMV particles containing the replication-defective RNA. Recently,
      it has been shown that human immunodeficiency virus type 1 (HIV-1) and simian
      immunodeficiency virus (SIV) Rev and Rev-responsive element (RRE) functions can
      be substituted in vitro by a cis-acting sequence, the constitutive transport
      element (CTE), from simian type D retroviruses like MPMV and simian retrovirus
      type 1 (SRV-1). To determine whether CTE of MPMV is necessary for MPMV nucleic
      acid propagation, an MPMV vector that lacked the terminally located CTE was
      generated. Propagation of this vector was completely abrogated in the absence of
      CTE, showing the importance of CTE in MPMV replication. Insertion of CTE back
      into the MPMV genome in the sense orientation rescued replication to wild-type
      levels. Slot-blot analysis of nuclear versus cytoplasmic RNA fractions revealed
      that most of the messages were sequestered in the nucleus of cells transfected
      with the CTE(-) vectors and very little was transported to the cytoplasm. To test
      whether HIV-1 or SIV RREs could complement CTE function, the HIV-1 or SIV RREs
      were inserted in the CTE(-) vectors, trans complementation of CTE(-)RRE(+)
      vectors with Env-and Rev-expression plasmids rescued propagation of the CTE(-)
      vectors. Computer analysis predicted an RNA secondary structure in MPMV CTE
      analogous to the HIV-1 and SIV RREs that could form three stable stem loops, the
      first of which contains a site similar to the Rev-binding domain in the HIV-1
      RRE. The presence of a higher-order CTE structure was analyzed by mutational
      analysis. We conclude that CTE is important in the replication of MPMV and
      affects the nucleocytoplasmic transport and/or stability of viral messages
      similar to the Rev/RRE regulatory system of HIV-1 and SIV.

PMID- 8874513
TI  - Molecular and pathogenic characterization of the RFB osteoma virus: lack of
      oncogene and induction of osteoma, osteopetrosis, and lymphoma.
AB  - RFB virus is an ecotropic C-type retrovirus isolated from CF-1 mice, in which it
      is associated with induction of osteomas. Sequence analysis of the RFB provirus
      revealed no evidence for presence of an oncogene or a recombined env gene. RFB
      virus is a member of the murine leukemia virus (MuLV) group (RFB MuLV), sharing
      97% nucleotide identity with the endogenous ecotropic provirus of AKR mice (Akv).
      Like Akv, expression of RFB MuLV mRNAs is inducible by dexamethasone treatment,
      indicating that FRB MuLV also shares transcriptional control signals with Akv. We
      assessed the pathogenic potential of RFB MuLV in NMRI mice, which, in contrast to
      CF-1 mice, do not contain endogenous ecotropic retroviruses. RFB MuLV induced
      osteomas, osteopetrosis, and lymphomas in newborn NMRI mice. Another CF-1 mouse
      derived leukemia virus, FBJ MuLV, the helper virus of the FBJ osteosarcoma virus
      stock, as well as Akv, also induced osteomas, osteopetrosis, and lymphomas in
      NMRI mice similar to RFB MuLV. These findings indicate that endogenous
      retroviruses carry a pathogenic potential in hematopoietic tissues and in the
      skeleton.

PMID- 8874514
TI  - P2 protein encoded by genome segment S2 of rice dwarf phytoreovirus is essential
      for virus infection.
AB  - Loss of infectivity to insect vector cell monolayers of rice dwarf phytoreovirus
      (RDV) after CCl4 treatment was associated with the removal of one of the viral
      proteins from the virus particles. This protein, encoded by genome segment S2 and
      thus named P2 protein, was located at the outer capsid of the virus particle.
      When RDV was treated with CCl4 for various times, the reduction in the amount of
      P2 protein and the loss of viral infectivity to vector cell monolayers were
      proportional to treatment time. RDV purified using CCl4 treatment thus lacking P2
      protein, lost the ability to infect vector insects through feeding and
      consequently failed to be transmitted to plants. These results suggest that P2
      protein is essential for RDV infection of the insect cells and may be related to
      transmission of the virus by the vector insect.

PMID- 8874515
TI  - CD44 is not required for poliovirus replication in cultured cells and does not
      limit replication in monocytes.
AB  - Although poliovirus receptor is required to mediate poliovirus infection, its
      role in mediating the tissue specificity of poliovirus replication in natural
      infections remains unclear due to the presence of this receptor in nonsusceptible
      cells. It has been hypothesized that CD44 has a role in determining the
      susceptibility of cell to poliovirus. To test this hypothesis, we determined
      whether HepG2, a cultured cell line that lacks cell surface CD44, can support
      poliovirus replication. We found that PV(1) Mahoney, PV(2)W2, and PV(3)Leon
      strains of poliovirus can replicate in HepG2 cells. Jurkat cells, which also lack
      CD44, support PV replication. These results suggest that CD44 is not required for
      poliovirus replication in cultured cells. To examine this question further
      expression of CD44 in primary human monocytes was examined. Greater than 90% of
      monocytes express the poliovirus receptor but only 6% of these cells are
      susceptible to poliovirus infection, making this a good system to study blocks to
      poliovirus replication. 97% of primary human monocytes reacted with a monoclonal
      antibody against CD44 that has been shown to block poliovirus binding and
      replication. This finding suggests that CD44 is present on more cells that
      poliovirus infects, making CD44 unlikely to be the factor limiting poliovirus
      replication in human tissues.

PMID- 8874516
TI  - Cloning and expression of a single-chain antibody fragment specific for foot-and
      mouth disease virus.
AB  - The gene for a single-chain antibody (VHK) to a conformational epitope on the
      type A12 foot-and-mouth disease virus (FMDV) particle was assembled and expressed
      in Escherichia coli. The VHK, purified from periplasmic extracts
      immunoprecipitated virus as efficiently as its parental monoclonal antibody (MAb)
      and exhibited the same binding specificity when tested against panel of natural
      and genetically engineered virus particles. The VHK neutralized type A12 virus in
      the presence of goat anti-mouse IgG; however, in the absence of the second
      antibody, only weak neutralizing activity was detected. Preliminary analysis of
      the mechanism of viral neutralization indicated that both the MAb and the VHK
      neutralize by the same mechanism. Small amounts of the VHK allowed infection of
      cells via Fc receptor-mediated adsorption in the presence of the second antibody.
      These data represent the first report of a single-chain neutralizing antibody for
      a picornavirus and provide insights into the mechanisms of viral neutralization
      and virus uptake.

PMID- 8874517
TI  - Molecular characterization of the segment 2 gene of epizootic hemorrhagic disease
      virus serotype 2: gene sequence and genetic diversity.
AB  - The complete nucleotide sequence of the gene encoding the major outer capsid
      protein VP2 from the Alberta isolate of epizootic hemorrhagic disease virus
      serotype 2 (EHDV-2) was determined. Complementary DNA (cDNA) corresponding to
      segment 2 was 3002 nucleotides in length with a single open reading frame that
      encoded a VP2 of 982 amino acids. Although the VP2 from EHDV-2 was only 34%
      homologous to the cognate protein from EHDV-1, their predicted hydropathic
      profiles were similar, suggesting that conservation of structure is important
      biologically to these capsid proteins. Sequence analysis of six North American
      EHDV-2 field isolates showed a high degree of comparative genetic identity (>
      97%). Phylogenetic profiles constructed suggest that regionalization of the
      viruses within the North American continent has contributed to the genetic
      diversity.

PMID- 8874518
TI  - Mutagenesis of conserved residues of the adenovirus protease.
AB  - Based on the alignment of 12 adenovirus protease sequences, we have identified
      eleven conserved residues for mutagenesis. Eight of these, E5, D26, N44, E71,
      D77, D102, N144, and N170, are potential candidates for the third residue of the
      active site triad. N44, E71, N144, and N170 proved to be essential for enzyme
      activity. Glutamic acid 71 was proposed for the active site. Mutation of the
      three conserved cysteines suggested that C122 is the active nucleophile, C104 is
      the target for activation by peptide pVIc, and C126 is dispensable. Rescue of
      enzyme activity of the C104 G mutant by pVIc suggested that disulfide bond
      formation between the peptide and the protease may not be absolutely essential
      for stimulation of enzyme activity.

PMID- 8874519
TI  - Efficient translation of distal cistrons of a polycistronic mRNA of a plant
      pararetrovirus requires a compatible interaction between the mRNA 3' end and the
      proteinaceous trans-activator.
AB  - Caulimoviruses, a type of plant pararetrovirus, employ a highly unusual mechanism
      to express the multiple cistrons of their pregenomic RNA. It involves translation
      of a polycistronic mRNA utilizing cis-acting viral RNA sequences and a
      transacting virus-encoded protein (P6). In addition to its role in polycistronic
      translation, the translational trans-activator protein P6 also activates its own
      expression from a monocistronic subgenomic RNA. Using Nicotiana Edwardsonii cell
      suspension protoplasts, we analyzed the ability of P6 proteins from three
      different caulimoviruses to activate viral RNA-based reporter constructs. Cis
      acting elements present in figwort mosaic caulimovirus (FMV) are functional not
      only in the presence of the cognate P6 activator protein, but also in the
      presence of the heterologous activators from cauliflower mosaic caulimovirus
      (CaMV) and peanut chlorotic streak caulimovirus (PCISV). However, when 3' cis
      acting elements essential for efficient polycistronic expression of FMV are
      replaced by their counterparts from PCISV, reporter gene expression is only
      observed in the presence of PCISV P6. Derepression of monocistronic reporter
      constructs tailed with FMV or CaMV 3' proximal sequences is less efficient in the
      presence of PCISV P6 than with either FMV or CaMV P6, but more efficient when the
      constructs contain a cognate PCISV 3' cis-element. Efficient expression of
      polycistronic and monocistronic caulimovirus mRNAs in plant cells thus requires
      compatible interactions between P6, a translational trans-activator, and its
      cognate cis-element at the 3' end of the mRNA.

PMID- 8874520
TI  - The N-terminal part of bacteriophage P2 capsid protein is essential for
      postassembly maturation of P2 and P4 capsids.
AB  - During capsid assembly of bacteriophage P2 and its satellite phage P4, gpN
      undergoes proteolytic cleavage with the removal of the first 31 amino acids. The
      truncated protein gpN* is unable to support formation of viable phages in
      complementation tests. A c-myc antigenic epitope (EQKLISEEDL) exchanged for
      eleven amino acids in the amino terminal part of gpN results in both proteolytic
      processing of gpN::c-myc as well as assembly of P2 and P4 procapsid-like
      structures, but gpN::c-myc failed, like N*, to support the production of
      infectious P2 and P4 particles.

PMID- 8874521
TI  - Murine leukemia virus infects early bone marrow progenitors in immunocompetent
      mice.
AB  - Chronic murine leukemia viruses (MuLVs) are retroviruses which induce
      leukemias/lymphomas after long latency periods. The induction of leukemia by
      MuLVs is complex, requiring multiple steps beginning with infection of an
      appropriate target cell. A number of investigators have proposed a bone marrow
      thymus axis in the development of retrovirus induced T-cell lymphoma in which
      cells are initially infected in the bone marrow. These bone marrow cells or their
      progeny migrate to the thymus during the disease process. In our system using
      adult, immunocompetent BALB.K mice infected with E-55(+) MuLV, a similar pattern
      is seen; integrated virus is initially detectable in the bone marrow and spleen
      and only later in the thymus. In order to better understand the leukemic process,
      we analyzed the bone marrow from adult, immunocompetent BALB.K mice infected with
      the E-55(+) MuLV in bone marrow colony assays. The results from these assays
      demonstrate that either a pluripotent progenitor cell or an early progenitor cell
      is a target in the bone marrow for the virus.

PMID- 8874522
TI  - Cosmetic therapy with botulinum toxin, Anecdotal memoirs.

PMID- 8874523
TI  - Tumors with smooth muscle differentiation.
AB  - BACKGROUND: In the classification of tumors of soft tissue, modern schemes
      describe tumors by the normal adult tissue type the tumor resembles. Thus, tumors
      are described as smooth muscle tumors if the cells are differentiating towards
      smooth muscle. We may infer that in fact the tumor arose from smooth muscle, but
      this is only an inference. Tumors showing differentiation towards smooth muscle
      include hamartomas, benign tumors, and malignant tumors. OBJECTIVE: This review
      article describes the clinical presentation and course, histology, and treatment
      recommendations for benign and malignant smooth muscle tumors. METHODS: An
      extensive literature review of tumors with differentiation towards smooth muscle.
      RESULTS: Benign tumors exhibiting differentiation towards smooth muscle include
      smooth muscle hamartoma and leiomyoma. Myofibroma is a third tumor that some have
      argued is a smooth muscle tumor rather than a fibroblastic tumor. Characteristic
      fusiform shaped cells with a round central nucleus arranged in fasicles suggest
      smooth muscle differentiation. Special stains such as phosphotungenistic acid
      hemotoxilin, analine blue, and Masson's trichrome are helpful in differentiating
      muscle from collagen. Immunohistochemical stains are also helpful in establishing
      a diagnosis. With solitary tumors, treatment for cosmesis or for painful
      leiomyomas is not a problem. Multiple leiomyomas, which may be painful or
      sensitive to cold or touch, are a therapeutic challenge, with reports of multiple
      medications being attempted in the literature. Leiomyosarcoma are malignant
      tumors of smooth muscle. They may be cutaneous and presumably arise from the
      arrector pilorum muscle, or subcutaneous, where they are believed to arise from
      vascular smooth muscle. Cutaneous leiomyosarcomas frequently reoccur following
      excision, but rarely metastasize. Subcutaneous leiomyosarcomas frequently reoccur
      following excision and have a high metastatic rate. Several recent reports have
      documented an increased frequency of visceral leiomyosarcomas in immunosuppressed
      patients. These tumors have been found to contain the Epstein Barr virus.
      Treatment of leiomyosarcoma is wide excision. CONCLUSIONS: Smooth muscle tumors
      are rare neoplasms that may confront the dermatologic surgeon. While leiomyomas
      are benign, their frequent sensitivity or pain necessitates treatment.
      Leiomyosarcomas are malignancies with a high reoccurrence rate, and when deep, a
      high metastatic rate. The finding of an increased frequency of visceral
      leiomyomas and leiomyosarcomas in immunosuppressed patients may imply an
      increased frequency of cutaneous leiomyomas and leiomyosarcomas in this patient
      population.

PMID- 8874524
TI  - Ultrasound-guided thermocouple placement for cryosurgery.
AB  - BACKGROUND: Although cryosurgical methods have high cure rates, imprecise
      estimates of both skin lesion depth and destructive temperature front location
      result in subjective technique in skin malignancy treatments. OBJECTIVE: We
      evaluated the possibility of newer ultrasound equipment to assist in the precise
      placement of thermocouples in human skin. METHODS: DermaScan C ver. 3
      ultrasonographic equipment fitted with a sharp focus probe with a frequency of 20
      MHz and a scan length of 12.1 mm was used to locate thermocouples with 27- and 30
      gauge needles. RESULTS: We successfully and reproducibly located thermocouples
      and thin needles, and accurately measured their distance from the skin surface.
      CONCLUSION: Ultrasound is a useful method for the accurate placement of
      thermocouples, and needles as thin as 30 gauge for monitoring in cryosurgery.

PMID- 8874525
TI  - A randomized controlled trial of hydrocolloid dressing in the treatment of
      hypertrophic scars and keloids.
AB  - BACKGROUND: Silicone gel sheeting has been investigated for use in the treatments
      of keloids and hypertrophic scars. Its mechanism of action may be related to scar
      hydration. OBJECTIVE: The purpose of the present study was to evaluate a
      hydrocolloid occlusive dressing that also acts by promoting a moist environment.
      METHODS: In a randomized controlled prospective study, patients were allocated to
      receive hydrocolloid dressing or moisturizer to keloids or hypertrophic scars.
      Scar size and volume, color, patient symptoms, and transcutaneous oxygen
      measurements were taken. RESULTS: There was significantly reduced itching (P <
      0.03), somewhat reduced pain (P < 0.08) and increased pliability (10%) for both
      treatments over 2 months. CONCLUSION: Hydration of the scar for 2 months resulted
      in symptomatic improvement, but no change in physical parameters.

PMID- 8874526
TI  - A clinical and histologic evaluation of two medium-depth peels. Glycolic acid
      versus Jessner's trichloroacetic acid.
AB  - BACKGROUND: Chemical peels using alpha hydroxy acids have become one of the most
      frequently requested dermatologic procedures. The use of glycolic acid in
      superficial chemical peels is now well established. However, the role of glycolic
      acid in medium-depth chemical peels has yet to be elucidated. OBJECTIVE: We
      performed a clinical and histologic comparison of 70% glycolic acid versus
      Jessner's solution as part of a medium-depth chemical peel using 35%
      trichloroacetic acid (TCA). METHODS: Thirteen patients with actinic keratoses,
      solar lentigines and fine wrinkling were evaluated prospectively. Each patient
      was treated with 70% glycolic acid plus 35% TCA (GA-TCA) to the right face and
      Jessner's solution plus 35% TCA (JS-TCA) to the left face. Clinical and
      histologic changes were evaluated at 7, 30, and 60 days postoperatively. RESULTS:
      Clinically, the GA-TCA peel was effective in treating photodamaged skin. The GA
      TCA peel was slightly more efficacious in removing actinic keratoses (clinical
      response score = 1.5) than the JS-TCA peel (clinical response score = 1.0).
      Histologically, the GA-TCA peel caused the formation of a slightly thicker Grenz
      zone (mean = 0.053 mm) 60 days postpeel than the JS-TCA peel (mean = 0.048 mm)
      (not statistically significant). The GA-TCA peel caused more neoelastogenesis
      than the JS-TCA peel, while the JS-TCA peel resulted in more papillary dermal
      fibrosis and neovascularization than the GA-TCA peel. CONCLUSION: The GA-TCA peel
      is a new medium-depth chemical peel that is effective in treating photodamaged
      skin.

PMID- 8874527
TI  - Linear grafting using a modified slot method. Introducing the linear punch.
AB  - BACKGROUND: As the field of hair transplantation changes radically almost month
      to month, one goal remains essentially unchanged-satisfy the patient. Mega
      sessions of only one to three hair grafts either by slit or laser produce a
      natural but thin result, while the more traditional circular punch grafting can
      produce a thicker but unnatural result. OBJECTIVE: To introduce a new type of
      recipient site that has the width of a micro graft but can vary in length. When
      linear grafts are placed into these new recipient sites, they produce strips of
      hairs that heal quickly and naturally. When using the multiblade knife for donor
      strip harvesting, the shape of grafts change from the traditional round grafts to
      a narrow linear strip of hair. Current methods of slit receptor sites accommodate
      these grafts better than circular punch sites when grafts with a small numbers of
      hairs are used. Unfortunately, with either larger slit grafts or later
      densification, slit grafts often tend to compress creating a pitted or tufted
      appearance. It is the authors' opinion that by creating a slot incision and
      removing some tissue, a more dense, natural appearance can be created for the
      patient obviating the problems with slits, lasers, or circular punch grafting.
      METHODS: One-year study on 100 hair transplant patients. CONCLUSION: The linear
      punch creates recipient sites that avoid compression and allows for more hairs
      per graft without compromising naturalness. Healing is comparable to micrografts
      alone. It is the authors' opinion that a linear or elongated slot incision
      accommodates grafts created from donor strip harvesting more naturally than
      slits, small round incisions or punctures. The linear graft created is the
      precise size and shape to the recipient slot incision to which it is placed. This
      technique helps us avoid the old adage, "Trying to fit a square peg into a round
      hole." As stated by Unger, a slot incision created by a Ultrapulse laser produces
      superior results to those seen with conventional slit grafting (Dermatol Surg
      1995;21:759-65). This approach is cost efficient and cosmetically appealing to
      the patient without the fear of the old "cornrow" appearance.

PMID- 8874528
TI  - Dermatologic laser surgery. A review.

PMID- 8874529
TI  - Laser treatment of scars.

PMID- 8874530
TI  - Posttransplant cysts.

PMID- 8874531
TI  - Localized cellular inflammatory responses to subcutaneously implanted dental
      mercury.
AB  - Previous reports have demonstrated mercury accumulation and toxicity in oral
      tissues following exposure to mercury vapor from dental amalgam restorations. In
      the present study, inflammatory responses to subcutaneously administered mercury
      were assessed histopathologically and immunocytochemically in a rat model system.
      A panel of six well-characterized monoclonal antibodies specific for monocytes,
      macrophage subsets, T and B lymphocytes, and major histocompatibility complex
      (MHC) class II (la) determinants was used to quantitate alterations in
      mononuclear cell subsets in situ at time intervals from 2 d to 8 wk. The results
      revealed acute inflammatory cell infiltration at 2 and 3 d, followed by chronic
      inflammation that persisted after 8 wk. The numbers of monocytes, resident
      macrophage subsets, and mononuclear cells expressing la antigen were
      significantly different from control tissues at 1-2 wk. The numbers of resident
      macrophages remained significantly higher even after 8 wk. These data showed that
      in situ mercury accumulation can lead to altered expression of MHC class II
      determinants with persistent chronic inflammation and shifts in mononuclear cell
      subpopulations.

PMID- 8874532
TI  - Reaction of human hemoglobin toward the alkylating agent S-(2
      chloroethyl)glutathione.
AB  - In order to investigate if hemoglobin might serve as a biomarker of exposure for
      1,2-dichloroethane (DCE) encountered in the workplace, human hemoglobin was
      alkylated at physiologic pH by the episulfonium ion of S-(2
      chloroethyl)glutathione (CEG). In vitro alkylation resulted in three alkylation
      products on the alpha chain and at least two alkylation products on the beta
      chain as determined directly by matrix-assisted laser desorption-ionization mass
      spectrometry. To ascertain if the site of alkylation was the reactive sulfhydryl
      present at cysteine-93 on the beta chain of hemoglobin (beta-93 Cys), a
      spectrophotometric assay using 4,4'-dithiodipyridine was used to measure the free
      sulfhydryl groups before and after treatment of hemoglobin with various amounts
      of CEG. Results indicate that the episulfonium ion did not react substantially at
      beta-93 Cys, as there was no measurable decrease in the sulfhydryl to hemoglobin
      ratio, even with a large excess of CEG. In contrast, iodoacetamide did react with
      the sulfhydryl groups and gave a dose-dependent decrease in the sulfhydryl to
      hemoglobin ratio as measured by this assay. CEG-treated hemoglobin was digested
      with Staphylococcus aureus endoproteinase Glu-C and the digest was analyzed by
      fast atom bombardment mass spectrometry. Only one peak in the FAB mass spectrum
      could correspond to a peptide modified by the episulfonium ion of CEG. These
      results indicate that although the episulfonium ion of CEG does alkylate human
      hemoglobin, beta-93 Cys is not the major alkylation target.

PMID- 8874533
TI  - Protective effects of glutathione on bromodichloromethane in vivo toxicity and in
      vitro macromolecular binding in Fischer 344 rats.
AB  - Bromodichloromethane (BDCM), a carcinogenic water disinfection by-product, has
      been shown to be metabolized to intermediates that covalently bind to lipids and
      proteins, and this binding has been associated with trihalomethane-induced renal
      and hepatic toxicity. In this study, the effects of glutathione (GSH) on in vivo
      BDCM toxicity and in vitro BDCM macromolecular binding were evaluated. The in
      vivo toxicity of BDCM in animals pretreated with buthionine sulfoximine (BSO, a
      glutathione synthesis inhibitor) and in untreated male Fischer 344 rats was
      investigated. In another experiment, covalent binding to protein and lipid was
      quantified after [14C]BDCM was incubated with hepatic microsomal and S9 fractions
      and renal microsomes from F344 rats, under aerobic and anaerobic conditions, with
      and without added GSH. After oral dosing with BDCM, the BSO-pretreated animals
      had greatly increased levels of serum indicators of hepatotoxicity and serum and
      urinary indicators of nephrotoxicity compared to those in animals dosed solely
      with BDCM. Histopathological examination revealed that hepatic necrosis was more
      severe than renal necrosis in the BSO-treated rats. When GSH was added to an
      aerobic incubation, protein binding was decreased in hepatic microsomal and S9
      fractions by 92 and 83%, respectively. GSH also decreased lipid binding by 55% in
      hepatic microsomal incubations carried out under anaerobic conditions. Addition
      of GSH decreased renal microsomal protein (aerobic) and lipid binding (anaerobic)
      by 20 and 43%, respectively. These data indicate that GSH is an important
      protective factor in the toxicity associated with BDCM.

PMID- 8874534
TI  - Lactational passage of fusaric acid from the feed of nursing dams to the neonate
      rat and effects on pineal neurochemistry in the F1 and F2 generations at weaning.
AB  - Fusaric acid is produced by several species of Fusarium and is found in corn,
      corn-based foods and feeds, wheat, barley, and other cereal grains. Given
      parenterally to rats, the mycotoxin affects neurochemical parameters in the
      pineal gland associated with growth and maturation. Since little information
      exists concerning the dietary effects of fusaric acid, the mycotoxin was mixed
      with feed at 10, 75, and 200 ppm and fed ad libitum to pregnant rats (F0 dams)
      from d 11-12 of gestation, through parturition and weaning (F1 generation). On d
      4 postpartum, F1 pups were culled to 9-10 pups/litter; the stomach colostrum was
      collected from the culls and analyzed for fusaric acid. The mycotoxin in the
      colostrum (ng fusaric acid/100 mg colostrum) was directly related to the amount
      consumed by the nursing dams (i.e., 200 ppm pups, 3547 ng; 75 ppm pups, 1449 ng;
      10 ppm pups, 80 ng; controls pups, 18 ng). All other animals survived, and
      appeared normal, healthy, and in good pelage. F0 dam feed consumption and dam and
      pup weights were not statistically different, but there was an inverse relation
      between pup average weight gain and amount of fusaric acid in the diets (i.e.,
      weight gains: control pup > 10 ppm pup > 75 ppm pups > 200 ppm pups). At weaning,
      the F1 pups were randomly assigned to two groups per treatment: one group (F1A)
      for reproduction and fusaric acid effects on the F2 generation, and another group
      (F1B) for neurochemical comparisons. The F1A rats were maintained on their
      respective diets to age 13-14 wk; animals were bred (i.e., control males x
      control females, 10 ppm x 10 ppm, etc.) and the F1A dams and F2 pups were
      monitored as already described. Weight gains and fusaric acid in stomach
      colostrum from the F2-culls were analogous to the F1 generation. On d 5-6 and 7-8
      postpartum, using litter weight gains as an indication of milk production in the
      F1A dams (controls vs. 200 ppm), the controls gained 32.5% (p < .01) and 13.3% (p
      < .02), respectively, more than 200 ppm F2 pups. At weaning, no differences were
      observed in neurochemicals in the pineal gland for the F1 generation. However, in
      the F2 200 ppm male and female weanlings, fusaric acid decreased pineal serotonin
      (males, p < or = .001; females, p < or = .15) and tyrosine (males, p < or = .04;
      females, p < or = .07). The results indicate fusaric acid in diets at < or = 0.3
      ppm (i.e., background control diet) lactationally passes from nursing dams to the
      neonate; in weanlings, at 200 ppm, fusaric acid decreases pineal serotonin and
      tyrosine. The data also suggest limited neonate weight gains may be related to
      either decreased milk production in dams or mycotoxin effects on the neonate.
      This is the first report of fusaric acid's lactational passage from the feed of
      nursing dams to neonates and the oral suppression of pineal serotonin and
      tyrosine in offspring.

PMID- 8874535
TI  - Subchronic dispositional and toxicological effects of arsenate administered in
      drinking water to mice.
AB  - Exposure to the drinking water contaminant arsenate is a daily occurrence and
      there are concerns that this exposure may lead to cancer. Although the acute
      dispositional effects of arsenate have been studied in detail, there is minimal
      information on the disposition and toxicological effects of it after continuous
      exposure. The objective of this study was to examine in mice the effect of a 4-wk
      treatment with arsenate administered in drinking water. Female B6C3F1 mice
      (3/cage) were housed in metabolism cages and given water and food ad libitum. Two
      groups (A, B) of mice were treated (4 cages/treatment/group) with distilled water
      (control, C) or water containing 0.025 mg/L (L) or 2.5 mg/L (H) arsenate. Group A
      was sacrificed on d 28 and plasma and urine samples were taken for determination
      of clinical chemistry parameters. Liver and kidney tissue samples were taken for
      histopathological analysis. The reduced nonprotein sulfhydryl (NPSH) content in
      several tissues was determined. Group B was gavaged with [73As]arsenate on d 28
      and continued the arsenate drinking water exposure for 48 h. Excreta and tissues
      were collected and analyzed for 73As. Urine was further analyzed for arsenate and
      its metabolites. There were no effects on the mean daily amount of water and food
      consumed, whereas the mean daily urine volume excreted was significantly elevated
      by 10% in the H-treated animals compared to C and L. A dose-related hepatic
      vacuolar degeneration in the liver was observed, but no histological changes were
      evident in the kidney. Only clinical chemistry parameters in plasma were altered
      by the arsenate treatment. Glucose was significantly lower at the H dose compared
      to C and L, triglycerides were significantly greater in C than L and H, and
      creatinine was significantly greater in H than C. Hepatic NPSH content in the H
      animals was significantly lower than C and L animals, whereas no effects in lung
      and kidney were detected. The weights of liver, lung, and kidney, as well as
      their tissue/body weight ratios, were significantly decreased in the H animals.
      73As was primarily eliminated in urine, and its elimination was not affected by
      dose. No effects on the 48-h 73As cumulative excretion (urine+fecal) were
      detected. The 73As distribution was low in amount and widely dispersed throughout
      the animal (< 3% of the 73As dose). The kidney had the highest 73As concentration
      of the tissues (0.01% 73As dose/g tissue). Dimethylarsinic acid was the major
      metabolite detected in urine, with lower amounts of arsenate arsenite, and
      monomethylarsonate. There were no differences between the treatment groups in the
      amount of urinary metabolites after a single dose of [73As]arsenate. Several
      toxicological effects were observed in animals administered arsenate in drinking
      water, but no changes in the disposition of this arsenical were detected at the
      doses used in this study.

PMID- 8874536
TI  - Characterization of inhibition by chronic treatment with lithium ion on nerve
      growth factor-induced neuronal differentiation of rat PC12 pheochromocytoma
      cells.
AB  - To understand the mechanism underlying the neurotoxicity of lithium ion, we
      investigated the inhibition of the nerve growth factor-induced neuronal
      differentiation of rat PC12 pheochromocytoma cells induced by treatment with
      LiCl. Incubation with 0.1-3 mM LiCl from 30 min before nerve growth factor (NGF)
      treatment attenuated neurite outgrowth. Moreover, incubation with 3 mM LiCl from
      24 h before strongly reduced the neurite out-growth. The chronic pretreatment
      inhibited the NGF-caused induction of acetyl-cholinesterase activity known to be
      elevated by NGF in transcription-dependent processes, and inhibited expression of
      c-fos proto-oncogene mRNA. This pretreatment also inhibited the NGF-induced
      formation of inositol phosphates, accompanied by the significant accumulation of
      inositol monophosphate. These observations, that chronic treatment with LiCl
      inhibits the NGF-induced neuronal differentiation in a transcription-dependent
      manner and inhibits phosphoinositide metabolism, suggest a possible causal
      relationship between these two events.

PMID- 8874537
TI  - Developmental toxicity study in rats exposed dermally to clarified slurry oil for
      a limited period of gestation.
AB  - Clarified slurry oil (CSO, CAS number 64741-62-4), a refinery stream produced by
      processing crude oil, is a developmental toxicant when administered dermally
      throughout gestation to pregnant rats. The manifestations of developmental
      toxicity observed included embryolethality and growth retardation; evidence of
      teratogenicity was limited, and not conclusive. The present study was undertaken
      to further explore the teratogenic potential of CSO. In an attempt to limit
      embryolethality and thereby promote detection of terata, CSO was administered
      once daily for a limited period of gestation [gestation days (GD) 9-12], via
      dermal application, to pregnant Sprague-Dawley rats at doses of 0, 10, 100, and
      1000 mg/kg. All animals were sacrificed on GD 20. Detailed examination of the
      dams was performed. Due to the screening nature of this investigation, fetal
      evaluations were limited to body weight measurements, external examinations, and
      evaluation of select visceral endpoints. In the dams exposed to CSO, significant
      decreases in body weight [absolute and gain (GD 9-13, GD 0-20)] and in the amount
      of food consumed were observed at 100 and 1000 mg/kg. Additional evidence of
      maternal toxicity observed at 1000 mg/kg included decreased absolute and relative
      thymus weights, increased absolute and relative liver weights, and aberrant serum
      chemistry. Ingestion of the test material was evident at the high dose.
      Developmental toxicity was observed at 1000 mg/kg and included increased
      embryolethality, decreased body weight, and anomalous development (cleft palate,
      brachydactyly, edema). Although a low incidence of abnormal fetal development was
      observed at 100 mg/kg, it was not conclusive that the alterations were due to CSO
      exposure. It is likely that three to seven-ring polycyclic aromatic compounds
      present in CSO were responsible for the toxic effects observed.

PMID- 8874538
TI  - EC-IC bypass 10 years later: is it valuable?

PMID- 8874539
TI  - The modified excimer laser-assisted high-flow bypass operation.
AB  - BACKGROUND: To make high-flow revascularization of the brain possible, we
      developed an anastomosis technique that obviates temporary occlusion of the
      recipient artery. After connecting donor and recipient vessels, an Excimer laser
      catheter, introduced by way of an artificial side branch, creates a hole at the
      anastomosis site. Because of the inconsistency of the diameter of the hole
      produced by the closed laser tip, we developed an extensive modification of the
      procedure. METHODS: A new type of laser tip was developed, consisting of two
      layers of 60 mu laser fibers in a circular configuration with a diameter of 2.2
      mm. The laser tip is fixed to the vessel wall at the anastomosis site by suction
      with a high-vacuum suction device, and a round piece of recipient vessel wall
      inside the anastomosis is cut out. RESULTS: Using the aorta as the recipient
      vessel in 30 rabbits, the modified technique was developed and, in the end,
      produced anastomoses with a high patency rate. In 25 patients, high-flow bypasses
      for different indications were made using a venous transplant interposed between
      the external carotid artery or one of its branches and the intracranial internal
      carotid artery, utilizing the modified Excimer laser technique for the
      intracranial anastomosis. Complications related to the new anastomosis technique
      were minimal, and a satisfactory patency rate was obtained. CONCLUSIONS: The
      modified Excimer laser-assisted anastomosis technique makes high-flow
      revascularization of the brain a safe procedure, since temporary occlusion of the
      recipient proximal brain artery during the making of the anastomosis is obviated.

PMID- 8874540
TI  - Cerebral revascularization using omentum and serratus anterior muscle free flap
      transfer for adult moyamoya disease: case report.
AB  - BACKGROUND: Use of the omentum in the treatment of moyamoya disease is now widely
      accepted, and, especially in patients with ischemic symptoms of anterior or
      posterior cerebral artery distribution, omental transplantation or other indirect
      revascularizations are indicated. CASE REPORT: A 39-year-old man, who developed
      left homonymous hemianopia, was discovered to have occlusion of the distal
      portion of bilateral internal carotid arteries. We performed indirect
      revascularization with an omental flap on the left cerebral hemisphere and a
      serratus anterior muscle flap on the right cerebral hemisphere. RESULTS:
      Subsequent clinical course was uneventful. Cerebral blood flow study and
      angiography revealed good collateral circulation in both the omentum and muscle
      flap. The collateral circulation was more developed than that arising from the
      omental transfer on the contralateral side at the same postoperative period.
      CONCLUSIONS: This type of encephalomyosynangiosis (EMS)-EMS with free muscle flap
      is as effective as that with the omental flap in adult moyamoya disease.
      Especially in a patient who is in need of vascular reconstruction of an extensive
      ischemic area, serratus anterior muscle flap transfer is one of the alternative
      methods.

PMID- 8874541
TI  - Xenon/CT quantitative local cerebral blood flow.

PMID- 8874543
TI  - Acute stroke therapies.
AB  - It is likely that thrombolytic agents will play a role in the management of acute
      ischemic stroke in well-selected patients, intravenous administration is most
      practicable. However, intra-arterial administration via superselective
      catheterization is an alternative option that may offer advantages is certain
      settings (e.g., angiography suite, intraoperatively). Tissue plasminogen
      activators appear safer than streptokinase. Fibrinolytic agents offer the
      unproven potential for improving stroke outcome with less risk of intracranial
      bleeding. LMWHs can be administrated subcutaneously with minimal blood
      monitoring. These agents may prove more useful for secondary stroke prevention
      rather than acute treatment. Introduction of other agents like monoclonal
      antibodies directed against leukocyte adhesion molecules, aspirin, or ticlopidine
      offer other potential approaches to improving stroke outcome.

PMID- 8874542
TI  - Putaminal and thalamic hemorrhage in ethnic chinese living in Hong Kong.
AB  - BACKGROUND: Hemorrhagic stroke is very common in the Chinese population, and it
      is one of the leading causes of mortality in Chinese communities. The risk
      factors to explain this high incidence are unknown. It is the purpose of this
      study to look into the features of hemorrhagic stroke in the Hong Kong Chinese.
      METHODS: We conducted a prospective hospital-based study in which 60 consecutive
      Chinese patients with computed tomography diagnosis of putaminal or thalamic
      hemorrhage were included. Their demographic and clinical data were collected and
      analyzed. RESULTS: Two major findings evolved from the present study. (1) Unlike
      the Western studies, the majority of our patients were about a decade younger;
      (2) 50% of the patients had previously diagnosed hypertension, but only 20% of
      these patients were compliant with their antihypertensive medication. Our results
      also suggested that low admission Glasgow Coma Scale scores, large hematoma size,
      and the presence of intraventricular blood were associated with poor outcomes.
      CONCLUSIONS: This study concludes that hemorrhagic stroke is indeed a serious
      health problem in Hong Kong. Simple measures, such as improvement of health
      education and the primary care system in the management of hypertension, would
      help to reduce the incidence of hemorrhagic stroke.

PMID- 8874544
TI  - CT angiographic-guided frameless stereotactic-assisted clipping of a distal
      posterior inferior cerebellar artery aneurysm: technical case report.
AB  - BACKGROUND: The development of frameless stereotaxis allows for repetitive
      intraoperative localization with millimeter accuracy. High-resolution computed
      tomographic (CT) angiography provides multiplanar, three-dimensional imaging of
      cerebral vascular lesions. The image data set generated during CT angiography can
      be used for localization in frameless stereotaxis when performed with appropriate
      fiducials in place. METHODS: The feasibility of melding these two technologies
      was tested on a patient with a small (5 mm), distal ruptured posterior inferior
      cerebellar artery aneurysm, which was visualized by CT angiography and localized
      by frameless stereotaxis. RESULTS: Visualization by CT angiography and
      intraoperative localization by frameless stereotaxis were successful.
      CONCLUSIONS: The practical application of this technology meld is demonstrated in
      this sample case. Applications to distal anterior cerebral artery aneurysms,
      abnormal flow-related aneurysms associated with arteriovenous malformations, and
      mycotic aneurysms are discussed.

PMID- 8874545
TI  - Epidural steroids for cervical and lumbar radiculopathy.

PMID- 8874546
TI  - Intraspinal meningiomas: review of 54 cases with discussion of poor prognosis
      factors and modern therapeutic management.
AB  - INTRODUCTION: Intraspinal meningiomas account for 25%-46% of primary spinal cord
      tumors. Technical advances in magnetic resonance imaging (MRI) and surgical
      procedures (ultrasonic cavitation aspirators [CUSA], lasers) have brought about
      better clinical results. In spite of these new techniques, a small percentage of
      patients still present with poor postoperative results and/or a recurrence. The
      authors tried to determine which data could influence clinical outcome and what
      therapeutic modalities could limit recurrence rate. MATERIALS AND METHODS: We
      reviewed 54 patients who from 1963 to 1994, each had surgery for an intraspinal
      meningioma. There were 43 females and 11 males, aged 8 to 85 years old. Thirty
      six (66.6%) patients were ambulatory on admission; only 2 presented with a
      paraplegia. Tumor location was cervical in 10 cases, thoracic in 43 cases, lumbar
      in 1 case. Forty-seven tumors were intradural, 5 epidural, 2 epidural and
      intradural. Thirty patients underwent a myelography, 10 a computed tomography
      (CT) scan, and 14 an MRI. Twenty-three spinal angiographies were performed before
      surgery. Complete removal was achieved in 50 patients (92.6%). Ultrasonic
      cavitation was used 10 times for debulking the tumor, and laser was used in 12
      surgical procedures to perform hemostasis of the meningioma and to coagulate the
      dural attachment. RESULTS: The majority of the neoplasms were meningothelial (N =
      24) or psammomatous (N = 11). No mortality was noted. Morbidity concerned five
      patients: two pulmonary embolisms, one definitive paraplegia, one transient
      deficit, and one epidural suppuration, which necessitated a second operation.
      Mean follow-up was 28 months. Final functional results were very good in 85% and
      good in 13%; one patient (2%) worsened. Two recurrences were noted: one with
      clinical signs and the other with only CT-scan modifications. Both patients
      underwent complementary radiotherapy. DISCUSSION AND CONCLUSION: The authors
      discuss factors influencing functional results. Sex, pregnancy, pathologic
      diagnosis, and recurrence do not seem to have any influence. Calcification of the
      meningioma, as well as an anterior dural attachment, are pejorative factors. They
      insist on preoperative angiography and point out the advantage of using a CUSA
      and/or a laser to debulk and coagulate the tumor itself and its dural attachment.
      They propose radiation therapy as an adjuvant treatment or an alternative to
      reoperation, which could be hazardous for some patients when, for instance, a
      recurrence is located in a critical area or when the patient's general status is
      fragile.

PMID- 8874547
TI  - Craniosynostosis in neural tube defects: a theory on its pathogenesis.
AB  - BACKGROUND: In most cases, craniosynostosis is a sporadic occurrence of unknown
      etiology. Efforts to ascertain the exact, cause of this deformation often fall to
      reveal its origin and pathogenetic mechanism. Some previous reports have
      described isolated instances of the association of neural tube defects (NTD) and
      craniosynostosis, but in none of them has a causal relationship been established
      to explain this coincidence, apart from a fortuitous sequence of congenital
      defects. METHODS: We have reviewed the clinical records of 40 patients diagnosed
      with craniosynostosis who were studied at our hospital over a 22-year period, for
      the purpose of determining the possible etiologies of this cranial deformation.
      RESULTS: We found that three children with unilateral coronal synostosis had
      associated NTD-an incidence of 7.5%. Two children had cephaloceles and the third
      harbored a lumbosacral myelomeningocele. In these three cases, the
      craniosynostosis was noted immediately after birth and before the development or
      treatment of hydrocephalus. CONCLUSION: We think that there must be an
      alternative explanation for the association of craniosynostosis and NTD other
      than overdrained hydrocephalus or chance association. We advance the hypothesis
      that in these cases the cause of the premature coronal synostosis was the lack of
      cerebral expansion. Since brain expansion and intracranial pulse pressure
      determine the growth and shape of the overlying cranial vault, the dampening
      effect of the malformation sac (myelomeningocele or cephalocele) on the
      intracranial pressure and on the pulse pressure may lead to close contact of the
      affected bones and to the premature closure of the coronal suture. The
      possibility of fetal head constraint because of diminished fetal activity due to
      the NTD as a contributory factor is also suggested.

PMID- 8874548
TI  - Pneumosinus dilatans: a sign of intracranial meningioma.
AB  - BACKGROUND: Pneumosinus dilatans affecting the sphenoid and posterior ethmoid
      sinuses has been reported in association with spheno-orbital meningiomas and is
      believed by some authors be a sign of an adjacent meningioma. METHODS: We report
      the case of a 57-year-old man who developed progressive neurologic signs and
      symptoms consistent with a frontal lobe lesion. Neuroimaging studies revealed a
      large partially cystic mass at the base of the anterior cranial fossa that
      appeared to be invading the left frontal lobe and that was associated with
      pneumosinus dilatans of the adjacent left frontal sinus. RESULTS: Although the
      appearance of the mass by neuroimaging was thought to be most consistent with a
      malignant glioma, the lesion was found at craniotomy to be a benign
      meningothelial meningioma. CONCLUSIONS: Many previous cases of progressive optic
      neuropathy associated with pneumosinus dilatans affecting the sphenoid and
      posterior ethmoid sinuses have been found to be caused by adjacent optic nerve
      sheath meningiomas. This case provides further evidence that pneumosinus dilatans
      is a sign of intracranial meningioma.

PMID- 8874549
TI  - Cystic extra-axial cavernoma of the cerebellopontine angle.
AB  - Besides acoustic neuromas, the cerebellopontine angle harbors a wide variety of
      masses, named "nonacoustic neuroma tumors," as a whole. Although magnetic
      resonance imaging has much improved our ability to differentiate among posterior
      fossa lesions, misdiagnoses may still occur when facing rare, controversial
      cases.

PMID- 8874550
TI  - Total removal of a primary intracranial squamous cell carcinoma invading the
      brain stem.
AB  - BACKGROUND: Primary intracranial squamous cell carcinomas are extremely rare, and
      commonly manifest as malignant transformations of intracranial epidermoid cysts.
      METHODS: A case of primary squamous cell carcinoma invading the ventral brain
      stem and the trigeminal entry zone is described. The tumor was microsurgically
      totally removed via a paramedian supracerebellar approach. Three years after the
      operation the tumor recurred, and was again totally removed using the same
      approach. RESULTS: The patient showed no postoperative neurologic deterioration
      except for a transient deterioration of gait disturbances. The pathologic
      diagnosis was a recurrence of the squamous cell carcinoma. CONCLUSIONS: Since
      primary intracranial squamous cell carcinomas grow slowly and have a well
      demarcated capsule, total removal should be considered whenever possible.

PMID- 8874551
TI  - Pontine glioma with osteoblastic skeletal metastases in a child.
AB  - BACKGROUND: The development of systemic metastases from primary intracranial
      gliomas is rare. We report here a rare case of pontine glioma with osteoblastic
      skeletal metastases. CASE: This 12-year-old boy presented with a 4-month history
      of hoarseness, dysphagia, and a progressively ataxic gait. Cranial computed
      tomography (CT) and magnetic resonance imaging (MRI) revealed a brain stem tumor
      that was diagnosed as a low grade glioma by stereotactic biopsy. Twelve months
      later following chemotherapy and radiotherapy, neurologic examination and
      neuroradiologic studies disclosed a recurrence of the pontine glioma. Skeletal
      roentgenograms revealed widespread osteoblastic metastases in the skull,
      vertebral bodies, pelvis, and long bones. A specimen from the iliac bone
      demonstrated cells that were immunoreactive glial fibrillary acidic protein
      (GFAP). DISCUSSION: The mechanism of how glioma cells determine their biologic
      behavior at bony metastatic sites is not known. Infratentorial gliomas, which
      occur frequently in young patients and demonstrate active bony metabolism, may
      stimulate osteoblastic cells, and induce osteoblastic changes.

PMID- 8874552
TI  - Microsurgical resection of colloid cysts using a stereotactic transventricular
      approach.
AB  - BACKGROUND: Several surgical approaches have proven effective in the management
      of colloid cysts. Cited disadvantages of the transventricular route are its
      difficulty in patients with small ventricles, and the risk of postoperative
      seizures; advantages include the avoidance of interhemispheric retraction and
      venous injury, and callosal section in the transcallosal route. METHODS: We
      retrospectively evaluated patient outcomes after minimally invasive
      transventricular microsurgical resection. Twenty patients underwent computed
      tomography-guided stereotactic resection of a colloid cyst based on trajectory
      planning through the middle frontal gyrus. The mean patient age was 38 years
      (range, 14-65 years). The colloid cyst was discovered incidentally in one
      patient; two patients presented in coma. Fourteen patients (70%) had preoperative
      hydrocephalus. RESULTS: Total or near-total (only a small remnant of cyst wall
      left attached to the fornix or thalamostriate vein) cyst removal was achieved in
      all patients. Mean follow-up after surgery was 4.3 years (range, 0.5-11 years).
      All patients had an excellent outcome (100%) with return to full function or
      employment status. Postoperative morbidity occurred in one patient (5%) who
      sustained a small caudate nucleus hemorrhagic contusion associated with temporary
      hemiparesis. A single postoperative seizure occurred in one patient 5 months
      after surgery; no patient developed a persistent seizure disorder. CONCLUSIONS:
      This technique relies on the use of a precisely placed limited craniotomy, a
      small cortical opening (10-20 mm), a precise trajectory to the foramen of Monro,
      and standard microsurgical instruments. Stereotactic transventricular
      microsurgical resection provided safe and effective management of patients with
      colloid cysts, even in the absence of hydrocephalus.

PMID- 8874553
TI  - A step-wise protocol for stress ulcer prophylaxis in the neurosurgical intensive
      care unit.
AB  - BACKGROUND: Neurosurgical patients are at risk for stress induced gastric
      erosion. Clinical criteria for monitoring stress ulcer prophylaxis (SUP) efficacy
      and predicting clinical bleeding are limited. SUP in the neurosurgical intensive
      care unit (NSICU) was evaluated utilizing a multidisciplinary quality assurance
      program with defined criteria for therapy. METHODS: All patients admitted to the
      NSICU were managed using this protocol. Therapy was initiated with a single drug
      (cimetidine 300 mg IV every 6 hours, or continuous infusion up to 2400 mg/day) in
      136 evaluable cases. Combination therapy was implemented if continued gastric pH
      < 4 and guaiac positive aspirates occurred (N = 45). RESULTS: Significant
      correlations were observed between low gastric pH values and both GCS < 8 (P < or
      = 0.01) and length of ventilatory support (P < or = 0.005). Single agent therapy
      was more effective in patients with GCS > or = 8 (P < or = 0.001). Endoscopy was
      performed in 25 patients. No patient with GCS < 8 had pathologic lesions. The
      presence of asymptomatic gastrointestinal lesions was higher in patients
      requiring longer ventilatory support (P < or = 0.001) and intensive care unit
      stay (P < or = 0.0001). Patients requiring pentobarbital and vasopressors had
      statistically higher rates of clinical bleeding (P < 0.05). Patients with GCS < 8
      had increased rates of pneumonia (P < or = 0.005) with a higher pneumonia rate
      when treated with combination therapy (P < or = 0.05). Overall, the incidence of
      clinical bleeding was 3.7%. CONCLUSIONS: This protocol was effective for
      prospective monitoring of SUP efficacy and limited multiple drug therapy to
      patients at risk for clinical bleeding.

PMID- 8874554
TI  - Pathogenesis of hyponatremia following subarachnoid hemorrhage due to ruptured
      cerebral aneurysm.
AB  - BACKGROUND: Hyponatremia following subarachnoid hemorrhage (SAH) occurs due to
      the inappropriate secretion of antidiuretic hormone (SIADH). However, this
      condition is also sometimes associated with certain dehydration states. METHODS:
      To clarify the pathogenesis, daily values of urine volume, water balance, and
      sodium balance (Na Bal) were correlated with plasma levels of atrial natriuretic
      peptide (ANP), antidiuretic hormone (ADH), and plasma renin activity (PRA) in 31
      cases of SAH. RESULTS: Na Bal was markedly negative on days 2 and 3. Cumulative
      Na Bal showed continuous negative values until day 10 following SAH. ANP values
      showed a consistent elevation, while ADH showed only an initial surge. PRA, as
      the gross indicator of circulatory volume, showed a lack of suppression,
      indicating no increase in the circulatory volume. CONCLUSION: Hyponatremia
      following SAH therefore appears to be the result of increased natriuresis, due to
      the inappropriate elevation of ANP rather than SIADH. In this situation, water
      restriction should not be recommended, since the circulatory volume is decreased.

PMID- 8874555
TI  - 48th Annual Meeting of The Neurosurgical Society of America June 4-7, 1995; Sea
      Island, Georgia.

PMID- 8874556
TI  - Paradoxic appearance of calcification on MRI.

PMID- 8874557
TI  - What is the most important problem facing neurosurgery in your country?

PMID- 8874558
TI  - Competition in neurosurgery: Part I.

PMID- 8874559
TI  - Surgical neurology on the Internet.

PMID- 8874560
TI  - The Helsinki Declaration, research guidelines and regulations: present and future
      editorial aspects.

PMID- 8874561
TI  - Myoelectric activity in the stomach and duodenum after epidural administration of
      morphine or bupivacaine.
AB  - BACKGROUND: Gastric emptying is delayed in patients receiving postoperative pain
      relief with epidural morphine compared to patients receiving epidural
      bupivacaine. The electrophysiological basis for this effect is unknown. The aim
      of this study was to compare the effects of epidural morphine with epidural
      bupivacaine on gastroduodenal myoelectric activity (EMG) in patients after
      surgery. METHODS: Fourteen patients with epidural analgesia who underwent open
      cholecystectomy were randomly assigned to receive either epidural morphine (EM)
      or epidural bupivacaine (EB) for postoperative pain relief. During surgery EMG
      electrodes were placed in the subserosa in the antrum and duodenum and the EMG
      registration started 3.5 hours after the end of surgery. Gastric emptying
      measured with the acetaminophen test was studied in the morning the day after
      surgery. RESULTS: The spike activity in the antrum was significantly lower 160
      340 minutes after the administration of morphine in the EM-group compared to the
      activity in the EB-group (P < 0.04). The incidence of regular slow wave rhythm in
      the antrum was significantly lower 160-520 minutes after the administration of
      morphine in the EM-group compared to the EB-group (P < 0.03). Duodenal Phase III
      activity measured with EMG was significantly more frequent during 160-520 minutes
      after the morphine administration in the EM-group compared to the EB-group (P <
      0.02). The acetaminophen absorption was significantly delayed in the epidural
      morphine group compared to the epidural bupivacaine group. CONCLUSIONS:
      Gastroduodenal electromyographic activity was significantly changed during
      epidural morphine compared to epidural bupivacaine. The delayed gastric emptying
      during epidural morphine may be explained by decreased and uncoordinated
      contractile activity in the antrum, shown by decreased spike activity and
      irregular slow wave rhythm. The increased pressure activity in the duodenum,
      shown by increased Phase III activity, may also impair gastric emptying.

PMID- 8874562
TI  - The effects of warming intravenous fluids on intraoperative hypothermia and
      postoperative shivering during prolonged abdominal surgery.
AB  - BACKGROUND: The infusion of several liters of crystalloid solution at room
      temperature may significantly contribute to intraoperative hypothermia because
      warming fluid to core temperature requires body heat. The aim of this study was
      to evaluate the effect of delivering warmed intravenous (IV) fluid to the patient
      on preventing intraoperative hypothermia. METHODS: Intraoperative core and mean
      skin temperatures were measured during prolonged abdominal surgery in 18 patients
      randomly divided into two groups according to intraoperative IV fluid management.
      In 9 patients (control group) all IV fluids infused were at room temperature. In
      the other 9 patients (group receiving warmed fluids) all IV fluids were warmed
      using an active IV fluid tube-warming system. In all 18 patients a warming
      blanket covered the skin surface available for cutaneous warming. Intraoperative
      changes in total body heat content (kJ) were calculated from core and mean skin
      temperatures. RESULTS: At the end of surgery, core temperature was 36.7 +/- 0.2
      degrees C in the group receiving warmed fluids and 35.8 +/- 0.2 degrees C in the
      control group (P < 0.05). The estimated reduction in heat loss provided by
      warming IV fluid was 217 kJ, a value very close to the theoretical value expected
      from thermodynamic calculation. During recovery, one patient shivered in the
      group receiving warmed fluids and seven in the control group (P < 0.05).
      CONCLUSION: In conclusion, infusion of warmed fluids, combined with skin-surface
      warming, helps to prevent hypothermia and reduces the incidence of postoperative
      shivering.

PMID- 8874563
TI  - Predicting postoperative adverse events. Clinical efficiency of four general
      classification systems. The project perioperative risk.
AB  - BACKGROUND: The Project Perioperative Risk in Gothenburg is a prospective
      clinical-epidemiological study designed to elucidate factors affecting the
      perioperative risk in unselected adult patients undergoing elective general or
      orthopaedic surgery. In this report on postoperative adverse events of varying
      severity, the predictive ability of four simple classification systems, ASA
      physical status, patient age, surgical stress and a visual analogue scale for
      intuitively appreciated global risk (RISK-VAS), is described. METHODS: 1361
      patients undergoing 1471 surgical procedures were subjected to a detailed and
      standardised preoperative assessment and classified according to ASA, age,
      procedure magnitude and RISK-VAS. Postoperative adverse events were prospectively
      registered during the entire hospital stay. RESULTS: The four classifications all
      correlated to postoperative adverse events. ASA physical status, RISK-VAS and
      patient age all appear to be more efficient in predicting severe than mild
      events, while surgical stress predicted severe events and mild ones equally well.
      CONCLUSION: The most efficient predictor of severe events appeared to be RISK
      VAS, where a relative risk of 28.1 of acquiring a severe postoperative adverse
      event could be demonstrated for those who had a score of 4 or more compared with
      those who had scores less than 4.

PMID- 8874565
TI  - The interaction between nitrous oxide and isoflurane on suppression of learning:
      a study using classical conditioning in rabbits.
AB  - BACKGROUND: Nitrous oxide (N2O) is commonly combined with a volatile agent for
      administration of general anesthesia. We studied the effects of N2O and
      isoflurane on learning of the rabbit nictitating membrane responses (NMRs).
      METHODS: Classical conditioning of the NMR was accomplished by presenting a 400
      ms tone conditioned stimulus before the presentation of a 100 ms shock
      unconditioned stimulus over 6 daily training sessions. The percentages of
      conditioned responses (CRs) were calculated for animals treated with 0% (n = 10),
      33% (n = 11), 67% (n = 11), and 75% (n = 7) N2O and for those treated with 0% (n
      = 8), 0.2% (n = 7), 0.4%, (n = 13) and 0.8% (n = 9) isoflurane separately. ED-50
      for suppression of learning for each drug were calculated. Percentages of CRs
      were calculated for treatments with combinations of 0.2% isoflurane with either
      32 or 48% N2O (n = 14, for each). RESULTS: Isobolographic analysis demonstrated
      that the combination of the two drugs exerted no greater effect than that seen
      with either agent administered alone; for well-established CRs (mean of days 5
      and 6), the estimated concentrations corresponding to a rate of 70% CRs were
      0.31% isoflurane with no N2O, 65.3% N2O with no isoflurane, and 0.2% isoflurane
      combined with 32.4% N2O. CONCLUSIONS: N2O and isoflurane interact additively on
      suppression of learning.

PMID- 8874564
TI  - Peroperative adenosine infusion reduces isoflurane concentrations during general
      anesthesia for shoulder surgery.
AB  - BACKGROUND: Adenosine (ADO), and stable analogs thereof, have been shown to exert
      antinociceptive action under experimental conditions in animals and in humans.
      The aim of this randomized double-blind placebo-controlled study was to evaluate
      if a low dose of intravenous (i.v.) ADO could reduce isoflurane requirements
      during joint-associated surgery, as an indication of antinociception in deep
      somatic pain. METHODS: Thirty-two patients, age 19-62 years, ASA I and II,
      scheduled for shoulder joint surgery, were assigned to receive an i.v. infusion
      of either adenosine, 80 micrograms.kg-1.min-1, or placebo, during the surgical
      procedure. Anesthesia was maintained with isoflurane/N2O/O2 inhalation. RESULTS:
      The peroperative isoflurane concentration was significantly reduced at 50 minutes
      of surgery in the group receiving adenosine infusion. Also, the systolic blood
      pressure level was peroperatively more stable during adenosine infusion than
      during placebo. Other clinical parameters, such as pain, postoperative analgesic
      requirements and nausea, were not different between groups. CONCLUSION: A
      peroperative infusion of a low dose of adenosine during shoulder joint surgery
      may reduce the peroperative isoflurane requirement.

PMID- 8874566
TI  - Heart rate variability in diabetic and non-diabetic renal transplant patients.
AB  - BACKGROUND: Heart rate variability (HRV) has been used to investigate the
      autonomic modulation of heart rate. Diminished HRV has been observed in diabetic
      autonomic neuropathy, a condition associated with increased mortality. Uraemia is
      associated with impaired autonomic function, but reports on the effects of
      uraemia on HRV are scarce. METHODS: HRV and its circadian variation were studied
      in 12 diabetic and 11 non-diabetic renal transplantation and in 12 control
      patients. HRV in time and frequency domains was determined from 24-hour ECG
      recordings. RESULTS: In the diabetic group, all time domain and frequency domain
      measures of HRV were markedly reduced (P < 0.05), when compared with the control
      group, and the circadian variation of HRV was absent. The mean (SD) amplitudes
      (ms) in the frequency bands were: high frequency: 3 (1), 6 (3) and 15 (3); low
      frequency: 9 (7), 16 (10) and 25 (8); very low frequency: 14 (8), 23 (12) and 30
      (11) in the diabetic and non-diabetic uraemic and in the control patients,
      respectively. In non-diabetic uraemic patients, a tendency to reduced HRV was
      observed, but no statistical differences in HRV measures were found when compared
      with the control group. CONCLUSION: The severe impairment of HRV in patients with
      end-stage diabetic nephropathy is probably due to autonomic neuropathy and partly
      also to the co-existing heart diseases. It may be a contributing risk factor for
      ventricular arrhythmias and sudden death in these patients. Uraemia alone causes
      similar but less severe changes in HRV.

PMID- 8874567
TI  - Comparison of the respiratory and systemic kinetics of nitrous oxide in the
      sheep.
AB  - BACKGROUND: To determine whether discrepancies in views on the kinetics of
      nitrous oxide (N2O) may have a methodological basis, we compared its kinetics,
      simultaneously, in the respiratory system and systemic circulation. METHODS: Six
      merino ewes (40-50 Kg) were previously prepared with catheters in the pulmonary
      artery and aorta. The animals were anaesthetised with thiopentone then ventilated
      on a mixture of 70% N2O, 1% halothane in oxygen for 4 h. Simultaneous serial
      arterial and pulmonary arterial blood samples were assayed for N2O by gas
      chromatography and respiratory gases were monitored continuously by mass
      spectrometry. RESULTS: Marked differences were observed between the respiratory
      and systemic kinetics of N2O uptake. While the expired/inspired N2O concentration
      ratio rose within 30 min to a value close to unity, the pulmonary
      arterial/arterial blood N2O concentration ratio did not reach unity during the 4
      h of each study, but approached a constant rate of uptake shown by the mean ratio
      of 0.94 (SD 0.01) from about 2 h onward. CONCLUSIONS: Discrepancies in fluid flow
      between respiratory gas and the cardiovascular systems, a concentration effect of
      N2O in the lungs, the relative solubility of N2O in blood and tissues, and
      ventilation/perfusion inequalities all may contribute to the observed
      differences. The ongoing uptake is consistent with persistent extrapulmonary
      losses. There remains a need for experimental data on the pharmacokinetics of
      N2O. Unequivocal studies on the disposition of N2O can be undertaken only by
      using direct measurement of fluxes of N2O across relevant organs or tissues.

PMID- 8874568
TI  - Effects of halothane, isoflurane and sevoflurane on calcium-related contraction
      in porcine coronary arteries.
AB  - BACKGROUND: Volatile anaesthetics have a direct inhibitory effect upon epicardial
      coronary arterial smooth muscles (1-4). The site and mode of their action at the
      cellular level need to be clarified, which was the purpose of our study. The
      present investigation attempted to answer the question in what way volatile
      anaesthetics influence Ca(2+)-related contraction in isolated porcine epicardial
      coronary to understand their intracellular mechanism. METHODS: Isolated helical
      strips of porcine epicardial coronary artery without endothelium were suspended
      for isotonic contraction recordings in Krebs-Ringer's solution. 9.4 x 10(-2) MK+,
      2.5 x 10(-3) M Ca(2+)-induced shortening of the strips was regarded as the
      reference value (100%). After incubation in Ca(2+)-free solution with 10(-3) M
      ethlene glycol bis (beta-aminoethyl ether)-N, N-tetraacetic acid (EGTA) for 60
      minutes, the muscle strips were exposed to increasing Ca2+ concentrations (10(-4)
      10(-2)) either in the presence or absence of 1.5 or 2.5 minimum alveolar
      concentration (MAC) halothane, isoflurane or sevoflurane, with 9.4 x 10(-2) M K+
      bath solution. RESULTS: All three drug groups produced apparent biphasic effects
      with a cumulative increase of Ca2+ concentration compared with control groups. An
      initial increase at low Ca2+ concentration was followed by a decrease of Ca(2+)
      activated contractions. Isoflurane affected Ca(2+)-induced contraction
      significantly more than halothane and sevoflurane. CONCLUSIONS: The results imply
      that volatile anaesthetics influence Ca(2+)-dependent activity of coronary smooth
      muscle by complex mechanisms, which involve promotion of intracellular Ca2+
      release and other mechanisms that alter sensitivity to calcium.

PMID- 8874569
TI  - Dextran 70 and blood loss during transurethral resection of the prostate.
AB  - BACKGROUND: Dextran is an effective plasma expander but also a potential
      anticoagulant. This article attempts to establish the clinical significance of
      any increased intra-operative blood loss associated with the use of dextran 70
      during transurethral resection of the prostate (TURP). METHODS: The blood loss
      was measured in used irrigating fluid by a photometer in 800 patients undergoing
      TURP. In 154 of them, 500-1,000 ml of 6% dextran 70 was given for volume
      replacement. A regression model was used to test for interactions between the use
      of dextran and the operative parameters that correlated independently with the
      blood loss. RESULTS: The bleeding varied between 10 and 3,825 ml (median 323).
      Operative parameters correlating to the blood loss were: weight of the prostatic
      resectate, operating time, irrigating fluid absorption, and systolic arterial
      blood pressure. The result of this regression analysis indicated that dextran did
      not increase the blood loss. Neither did the prostatic weight and operating-time
      corrected blood loss increase when dextran was infused. CONCLUSION: There was no
      indication that dextran 70 given within the recommended dose range increases the
      blood loss during TURP.

PMID- 8874570
TI  - Quantitative EEG analysis as a supplement to the clinical coma scale RLS85.
AB  - BACKGROUND: The aim of the study was to investigate the correlation between EEG
      indicators and clinical scores based on the RLS85 (Reaction Level Scale 85) in
      comatose patients. The results of a simple visual assessment of the EEG, using an
      arbitrary scale with typical EEG patterns, were compared with those obtained by
      quantitative electroencephalography (qEEG). METHOD: The RLS85 scores were
      examined in 34 patients with impaired consciousness due to brain tumours,
      vascular lesions or head injuries. The EEG was recorded shortly before or after
      the clinical examination. The semiquantitative assessment was made by visual
      inspection of the tracings, using an arbitrary scale where 12 EEG patterns with
      increasing proportion of slow activity were displayed. Parallel to the visual
      analysis, the EEGs were processed by means of EEG spectrum analysis and the
      power/amplitude in slow frequency bands was used as an indicator. The results
      were based on correlation between various types of EEG variables and the RLS
      scores which were obtained in the same patients. RESULTS: The correlation between
      the visual EEG indicators and coma scores ranged between 0.53 and 0.57 (P <
      0.01). As regards the computerised EEG analysis, the correlation between the
      clinical scores and various EEG spectrum values did not exceed 0.45 (P < 0.01). A
      higher correlation could be obtained by combining eight EEG variables; the
      multiple correlation coefficient was then 0.68. CONCLUSIONS: The amount of EEG
      slow activity is significantly correlated to the RLS85 score. This means that the
      EEG also provides information on the level and not only on the changes of the
      coma degree. Surprisingly, the indicators based on quantitative EEG, as used in
      commercially available instruments, did not give better results than the visual
      assessment. However, the results of the computerised analysis could be improved
      using multivariate statistical methods. The study also showed a way to improve
      communication between the neurophysiologist and clinician by presenting the EEG
      findings in terms similar to those used in the clinical scales. However, the
      clinician should be aware of the fact that the "EEG score" and the clinical score
      is not the same: the intention is to supplement rather than to simulate the
      clinical observation.

PMID- 8874571
TI  - Effects on skeletal muscle oxygenation and capillary blood flow by adenosine-,
      sodium nitroprusside- and acetylcholine-induced hypotension.
AB  - BACKGROUND: Adenosine (ADO)-induced hypotension during diethyl ether anesthesia
      has been shown to increase skeletal muscle oxygenation. Whether this beneficial
      effect of ADO hypotension is present also during another anesthetic technique was
      tested in the present study using ketamine-xylazine anesthesia, and its actions
      were compared with sodium nitroprusside (SNP) and acetylcholine (ACh) induced
      hypotension in rabbits. METHODS: Local oxygen pressure and capillary blood flow
      were measured with a multiwire microelectrode which was placed on the surface of
      the left vastus medialis muscle. The experiments were performed in three groups,
      in which either ADO, SNP or ACh was infused into a central vein in a dose that
      produced a reduction of the mean arterial pressure by 20-25%, to approximately 60
      mmHg. RESULTS: In the ADO group (60-170 micrograms kg-1 min-1) the tissue oxygen
      pressures increased by 23% while capillary blood flow decreased by 38%. During
      SNP administration (1-3 micrograms kg-1 min-1) the oxygen pressures decreased by
      21% and an increase of 31% in capillary flows was seen. When ACh was infused (1-4
      micrograms kg-1 min-1) the oxygen pressures decreased by 21% and, in parallel,
      capillary blood flow decreased by 50%. During hypotension no low tissue oxygen
      pressure values (< 1.5 kPa) were found in the ADO group, whereas they were
      present in both the SNP and ACh group. CONCLUSION: Compared to sodium
      nitroprusside and acetylcholine, adenosine appears to have an oxygen-sparing
      effect in the skeletal muscle during pharmacologically induced hypotension.

PMID- 8874572
TI  - Percutaneous dilatational tracheostomy.
AB  - METHODS: Fifteen patients electively selected for percutaneous dilatational
      tracheostomy as performed with the Ciaglia Percutaneous Tracheostomy Introducer
      Set are reported in this preliminary study. RESULTS: The median time for
      insertion of the tracheostomy tube was 13.9 min. Complications were cuff puncture
      of the translaryngeal tube at an early stage of the procedure in one case, and
      minor bleeding controllable by the compressible effect of the dilatational
      procedure in three cases. During the posttracheostomy period, complications were
      one case of minor bleeding controllable by digital compression and one case of
      minor infection, i.e. cellulitis in a few millimetres around the stoma without
      purulent secretion. CONCLUSIONS: Our preliminary results indicate the technique
      as performed with the Ciaglia Introducer Set to be effective and safe with only
      minor complications. Furthermore, we now use it as a bedside procedure in the
      ICU, thus avoiding the transportation of critically ill patients to the operating
      theatre. The conclusion of the superiority of percutaneous tracheostomy to
      dissectional tracheostomy has to await clinical randomized studies, including
      more patients.

PMID- 8874573
TI  - Analgesic effect of intraarticular morphine. A controlled, randomised and double
      blind study.
AB  - BACKGROUND: Opioids produce antinociceptive effect by acting on receptors on
      peripheral nerves. The clinical relevance of this effect is still debated. The
      aim of the study was to compare the analgesic effect of morphine intraarticularly
      with the intramuscular route of administration after knee surgery. METHODS: Sixty
      one patients, ASA 1-2, having elective arthroscopic surgery of the knee were
      randomised to either an intraarticular or intramuscular dose of morphine 5 mg.
      The pain sensation was estimated by visual analogue scale and a verbal rating
      score 0, 1, 2 and 4 hours postoperatively and verbal rating score on the third
      day. The use of acetaminophen and supplementary opioids were recorded for the
      first 4 hours postoperatively, from 4 hours until the third day, and from day 3
      to day 7 postoperatively. RESULTS: The groups were comparable. Three patients
      were excluded. There were no statistically significant differences in painscore
      and consumption of analgesics. Fifty-nine per cent in each group had macroscopic
      synovitis. In the intraarticular group, there was no increased effect of morphine
      in the patients with synovitis compared to patients without synovitis.
      CONCLUSIONS: The clinical analgesic effect of 5 mg morphine given
      intraarticularly is equal to 5 mg morphine given intramuscularly. The occurrence
      of villous synovitis seems to be of no clinical importance concerning the local
      effect of morphine.

PMID- 8874574
TI  - Pre-emptive effect of pre-incisional versus post-incisional infiltration of local
      anaesthesia on children undergoing hernioplasty.
AB  - BACKGROUND: Although promising in experimental studies of post-traumatic pain,
      the concept of pre-emptive analgesia is still controversial in a clinical
      setting. Thus, we wanted to compare the clinical efficacy of wound infiltration
      with local anaesthesia before surgery with wound infiltration after hernioplasty
      in children. METHODS: Fifty children aged 2-10 years scheduled for hernioplasty
      were randomly assigned into two groups. Group 1 (n = 28) was infiltrated before
      surgery with bupivacaine 2.5mg/ml, 1mg/kg after induction of general anaesthesia.
      After surgery they were infiltrated with the same volume of 0.9% saline. Group 2
      (n = 22) was infiltrated with 0.9% saline before surgery and bupivacaine 2.5
      mg/ml, 1mg/kg after surgery. The study was performed double-blindly. In both
      groups anaesthesia was induced with thiopenthone and maintained with nitrous
      oxide and halothane, adjusted to keep haemodynamic measurements stable. All
      children were given paracetamol 15-20 mg/kg rectally when admitted to the
      recovery ward. Painscore (OPS) and analgesic requirements were registered
      postoperatively. After 48 h the parents completed a standardised questionnaire
      and they were interviewed by telephone after one week. RESULTS: The pre
      incisional group needed significantly less halothane during the procedure
      compared with the post-incisional group (P < 0.05). The pre-incisional group also
      had a tendency towards faster awakening after the end of anaesthesia and a
      significantly lower OPS-pain score 30 min after the operation (P < 0.03). There
      were no differences between the two groups regarding need for additional
      analgesia: meperidine i.v. during the first 5 h postoperatively, and paracetamol
      thereafter. There were no differences between the groups regarding activity
      level, appetite and quality of sleep in the first week. In both groups the need
      for opioid analgesics was low: 54% in the pre-incisional group and 45% in the
      post-incisional group did not receive any opioid analgesic treatment. The
      children were virtually fully recovered after the first 24 h. CONCLUSION:
      Perioperative infiltration with a local anaesthetic in children undergoing
      hernioplasty results in a smooth recovery with little need for opioids
      postoperatively. Apart from a lower anaesthetic requirement and a reduced
      postoperative pain level after 30 min in the pre-incisional bupivacaine group,
      there was no difference between infiltration before (pre-emptive) or after
      surgery.

PMID- 8874575
TI  - Management of postoperative pain. An intervention study.
AB  - BACKGROUND: In 1989 a study had shown that the quality of postoperative pain
      treatment (PPT) in a district general hospital was not satisfactory. Therefore,
      new instructions for PPT were issued, intra-venous medication with morphine was
      introduced on the wards, and the staff was educated in PPT. The purpose of this
      study was to investigate the quality of PPT in 1992 compared to the quality in
      1989. METHODS: Using identical questionnaires, 191 patients in 1989 and 126
      patients in 1992 were interviewed before and 2-5 days after surgery regarding
      postoperative pain. At the postoperative interview patients in pain also filled
      out the McGill Pain Questionnaire. A questionnaire was also answered by the
      nurses regarding PPT in 1989 and in 1992. RESULTS: 1992 compared to 1989
      (1992/1989): all patients were now medicated (100%/93%), most of them regularly
      (79%/ 4%) and the majority (94%/15%) also received non-opioid analgesic. Fewer
      patients (65%/80%) experienced postoperative pain lasting more than one day
      following surgery. Analgesic prescription was more standardized. In 1992 the
      nurses were more satisfied than in 1989 with the PPT and the physicians'
      prescribing patterns. All the above-mentioned parameters were significantly
      improved from 1989 to 1992. All the different pain-scores showed a reduction (8
      30%) but did not reach statistical significance (P = 0.2). CONCLUSIONS: Our two
      investigations show that it is possible to improve the quality of pain management
      with rather simple reforms.

PMID- 8874576
TI  - Extradural abscess complicating lumbar extradural anaesthesia and analgesia in an
      obstetric patient.
AB  - A 33-year-old nulliparous woman with severe pre-eclampsia was treated with
      extradural analgesia to control blood pressure and relieve pain during delivery.
      Nine hours after extradural catheter insertion a Caesarean section was performed
      due to uterine inertia. The extradural catheter was kept in place for 88 hours.
      Ten days following the extradural block she developed an extradural abscess and
      had to undergo a laminectomy. In a retrospective and, in part, prospective
      analysis on more than 13,000 extradural blocks, we studied the incidence of this
      dreaded complication and reviewed the literature on clinical findings, diagnosis
      and treatment.

PMID- 8874577
TI  - Resistance followed by prolonged neuromuscular block with vecuronium.

PMID- 8874578
TI  - Transient radicular irritation after spinal anaesthesia.

PMID- 8874580
TI  - Clinicopathology of chondrosarcoma.
AB  - We conducted a clinicopathological analysis of chondrosarcomas in 17 patients
      treated in our institute. The 5- and 10-year overall survival rates of the
      patients were 72.3% and 61.9%, respectively. The significant prognostic factors
      were size and histologic grade of the tumor. Sex, age, location of the primary
      tumor, or the presence of a preceding exostosis did not affect the treatment
      results significantly. Chondrosarcomas of histologic grades I and II did not
      metastasize, while all grade III and dedifferentiated chondrosarcomas
      metastasized to the lung. The local recurrence rate depended on the surgical
      margin. Wide excision with an adequate surgical margin is important to achieve
      local control of the chondrosarcoma.

PMID- 8874579
TI  - Clinical applications of neurotransmitter-receptor studies in geriatric
      neuropharmacology.
AB  - The use of ligand-binding methods to study neurotransmitter-receptor sites has
      made its impact on almost all aspects of biological pursuits including research
      on aging and neurodegenerative diseases. In the past, most of the research in
      biochemical gerontology has largely centered around changes in various
      neurotransmitters and enzymatic activities. The molecular basis of aging and
      neurodegeneration at the level of neurotransmitter-receptor interactions has been
      highly appreciated in the last two decades as a result of receptor binding
      studies. It is now possible to obtain information about the regional distribution
      of neurotransmitter receptors in the brain, the pharmacological and biochemical
      characteristics of these sites, and the functional interrelationships between
      different neuronal systems in normal and pathological conditions. The passage of
      time after maturity is accompanied by measurable physiologic decline in virtually
      all systems. It is the aim of this work to discuss the practical aspects of
      neurotransmitter and/or drug (ligand)-receptor binding studies, highlighting some
      examples of their applications to geriatric neuropharmacology research, with
      special consideration to learning impairment and memory loss in normal and in
      pathological aging processes.

PMID- 8874581
TI  - Superoxide dismutase activity in cerebrospinal fluid and its relation to
      compression of the lumbosacral nerve root.
AB  - In the pathophysiology of lumbosacral radiculopathy, inflammation of the nerve
      root is of critical importance. Additionally, free radicals have been shown to be
      associated with some inflammatory process. This study was designed to investigate
      whether free radicals participate in the pathophysiology of nerve root
      involvement. We measured superoxide dismutase (SOD) activity in cerebrospinal
      fluid (CSF) of 31 patients with unilateral lumbosacral radiculopathy caused by a
      herniated disc using electron spin resonance (ESR) spectrometry. Then SOD
      activity was compared with the type of nerve root compression as seen on
      preoperative myelography. SOD activity in the normal control group was 7U/ml,
      while that in the hernia group remarkably decreased. The concentration gradient
      of SOD activity was different between central herniation and centrolateral
      herniation. Our findings indicate that free radicals are generated after nerve
      root compression. Under severe deficiency of SOD activity in CSF, serum SOD
      penetrates into CSF after further compression. In addition, SOD in CSF may play
      an important role in protecting against nerve root involvement.

PMID- 8874582
TI  - Platelet taurine concentration and uptake in the Brattleboro diabetes insipidus
      rat.
AB  - Since platelets accumulate taurine, they provide a model for studying the taurine
      transport in anisosmotic disorders. Thus, in this work we studied the taurine
      concentration and uptake in the platelets of Brattleboro rats, homozygous (DI)
      and heterozygous (HZ) for hereditary hypothalamic diabetes insipidus, and Long
      Evans (LE) normal rats after free water intake and after dehydration induced by
      water deprivation for 24 h. The decreased ability of the DI rats to concentrate
      urine led to plasma hypernatremia and hyperosmolality despite excessive drinking.
      Water deprivation in the DI rats induced drastic dehydration with exacerbated
      hypernatremia and hyperosmolality. Plasma hypernatremia and hyperosmolality
      resulted in a significant elevation of the taurine concentration and uptake by
      platelets of the DI rats. Kinetic assays showed that plasma hypernatremia and
      hyperosmolality did not alter the affinity of taurine to platelet membrane
      carrier, as expressed by Km, but caused a profound increase in the maximal
      transport capacity, Vmax. After free water intake the Vmax of the DI rats was
      about two times higher than that in the HZ and LE rats and after water
      deprivation it was about three times higher. Water deprivation doubled the Vmax
      of the DI rats without changing the Km.

PMID- 8874583
TI  - Capillary architecture in the skeletal muscles in the rat hind limb.
AB  - We observed differences in the capillary architecture of the skeletal muscles
      that have different fiber metabolism. The soleus, the vastus intermedius and the
      tibialis anterior muscles of adult Wistar rats were prepared using two different
      techniques. Samples for adenosine triphosphatase (ATPase) staining were prepared
      following Dubovitz's method, and the distributions of fiber type, Types 1, 2A and
      2B, were analyzed. Then, corrosion casts of capillary architecture of these
      muscles prepared following Murakami's method were observed with a scanning
      electron microscope (SEM) and compared with the fiber distribution. The fiber
      type composition of the soleus muscle showed Type 1 (slow-twitch) dominance and
      that of the vastus intermedius and the tibialis anterior muscle showed Type 2
      (fast-twitch) dominance. The capillaries of the soleus muscle were tortuous, and
      this was thought to be advantageous for blood supply. In contrast, the
      capillaries of the vastus intermedius and tibialis anterior muscles had a
      relatively parallel pattern. Additionally, two different patterns of capillary
      architecture that appeared to correspond to certain metabolic characteristic of
      different muscle fiber types were preserved with corrosion casting. In
      conclusion, comparative studies on capillary architecture of the skeletal muscles
      are useful for analyses of its function.

PMID- 8874584
TI  - Pharmacokinetic evaluation of omeprazole suspension following oral administration
      in rats: effect of neutralization of gastric acid.
AB  - In order to evaluate a clinical use of omeprazole suspension, we examined the
      pharmacokinetics of omeprazole after oral administration in rats. Although the
      administration of omeprazole suspension buffered by NaHCO3 solution did not
      produce a significant increase in the area under the concentration-time curve
      (AUC) value compared with non-buffered group, the administration of NaHCO3 buffer
      immediately after dosing of omeprazole suspension buffered by NaHCO3 caused a
      significant increase in the AUC value. These results suggest that the NaHCO3
      treatment following the administration of omeprazole buffered suspension
      effectively decreased the degradation of the compound by gastric acid. Therefore,
      the successive administration of NaHCO3 solution after the omeprazole dosing
      seems to be a simple and useful method for the administration to patients who
      cannot receive tablets.

PMID- 8874585
TI  - Changes in cellular ultrastructure induced by gamma-interferon in K562 cells may
      be prerequisite for apoptosis.
AB  - We report here the time-course of electron microscopic changes induced by gamma
      interferon (IFN-gamma) in the human erythromyeloid leukemia cell line K562. In
      K562 cells treated with IFN-gamma for 6h, the nuclei were polygonal in shape and
      microvilli were far more abundant on cell membranes compared with control K562
      cells, and invaginations were often seen in the cell membranes. There was a
      reduction in the number of cell-membrane microvilli and an increase in the number
      of lysosomal bodies in the cytoplasm of K562 cells treated with IFN-gamma for
      12h. After treatment with IFN-gamma for 24h, the cell membrane microvilli
      disappeared, large numbers of cellular organelles were observed, such as
      mitochondria and lysosomes, and the cytoplasm became electron-dense. Cytoplasmic
      vesicles and vacuoles were also observed. These vesicles may correspond to an
      intermediate step in the ultimate cellular disintegration associated with
      apoptosis caused by IFN-gamma.

PMID- 8874586
TI  - Variability of presentation in medial temporal lobe epilepsy: a study of 30
      operated cases.
AB  - INTRODUCTION: To evaluate the homogeneity of patients operated on for MTLE.
      MATERIAL AND METHODS: 30 consecutive patients prospectively investigated with
      clinical, EEG, neuropsychology, MRI, FDG-PET criteria and eventually intracranial
      EEG, who underwent antero-medial temporal resection (follow-up: 24 months).
      RESULTS: Clear and well-lateralised MTLE was non-invasively ascertained in 22
      patients (73%). Eight patients (27%) had a less pure presentation due to
      divergent scalp EEG features (bitemporal, widespread or extratemporal), unusual
      auras or absence of MRI-based hippocampal sclerosis or FDG-PET hypometabolism.
      They were explored by invasive monitoring which confirmed medial temporal origin
      of seizures. Outcome was excellent in 95% of the pure cases (Engel's class I) and
      less favorable in the more difficult ones (65% of class I). CONCLUSIONS: MTLE
      criteria, including the strong contribution of brain imaging, permit to select
      accurately a large percentage of patients. However a consistant number of
      patients present a less pure presentation suggesting more complex epileptogenic
      networks.

PMID- 8874587
TI  - Influence of vigabatrin on cognitive performances and behaviour in patients with
      drug-resistant epilepsy.
AB  - INTRODUCTION: The aim of this research was to evaluate changes in cognitive
      performances, mood and quality of life in drug-resistant epileptic patients,
      after the introduction of Vigabatrin (VGB) as additional treatment. MATERIAL AND
      METHODS: A four-step evaluation was carried out in two groups of 20 patients
      each, randomly assigned to VGB or placebo treatment. A battery of
      neuropsychological tests investigating attention, memory and adaptive abilities,
      associated with inventories concerning depression, quality of life and the
      concern of families upon patient behaviour, were utilised. For each subject, four
      evaluations were performed, two before and two after VGB/placebo administration.
      RESULTS: No relevant side-effects regarding cognition and behavior were detected
      in the VGB group. The intra-group comparison between pre- and post-treatment
      phases showed a slight improvement in cognitive performances of VGB patients and
      a positive change in their overall psychological status. The inter-group
      comparison confirmed the selective improvement occurring in the trend of a few
      neuropsychological test scores in the VGB group. CONCLUSION: Such results help to
      reject the hypothesis that the addition of VGB to the current antiepileptic
      treatment may affect cognitive performances and behaviour.

PMID- 8874588
TI  - Evaluation of epilepsy management in a developing country: a prospective study of
      407 patients.
AB  - 407 patients (248 men, 159 women) of epilepsy attending the neurology clinic were
      evaluated to find out the profile of epilepsy, cost-effectiveness of various
      investigations, therapeutic regimens and efficacy of referring physicians in a
      developing country. At the time of onset of seizures 67.2% of patients were in
      the second and third decade. Generalised tonic clonic seizures were the commonest
      seizure type seen. Specific aetiology was established in 20.8% cases only.
      Neurocysticercosis was the commonest cause observed. The main source of referral
      (50.1%) was general practitioners. Referral diagnosis was incomplete in 52.8% of
      the cases. Investigations did not alter the diagnosis in 62.5% cases. The EEG was
      useful in the management of 15.1% cases of epilepsy. The skull x-ray and chest x
      ray were abnormal in 1.7% and 2% cases respectively. CT scan revealed abnormality
      in 39.4% cases. Most of the patients were treated with monotherapy. Phenytoin,
      phenobarbitone and carbamazepine were the common drug used. Out of 246 cases who
      were started on anticonvulsant therapy prior to referral, the choice of drug was
      wrong in 78 (31.7%) cases and dose was inappropriate in 121 (49.2%) cases. It was
      concluded that most important factor for cost effective management of epilepsy is
      proper clinical evaluation and education of general physicians in this direction.

PMID- 8874589
TI  - Transcranial magnetic stimulation in partial epilepsy: drug-induced changes of
      motor excitability.
AB  - Single-pulse transcranial magnetic stimulation (s-TMS) with recording of motor
      evoked potentials (MEPs) from thenar muscles of both hands was performed on 84
      patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed
      the cortical latency (CL), central conduction time (CCT), and threshold intensity
      (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were
      normal, but TI was significantly higher than in the controls. Of the 84 patients,
      65 were taking one or more antiepileptic drugs and 19 were untreated. The
      untreated patients had a significantly lower TI than the treated patients. In the
      treated patients, the TI increase paralleled the number of drugs taken.
      Additionally, in 2 subgroups of patients undergoing major modifications of
      antiepileptic treatment, TI dropped after partial withdrawal of medication and
      increased following the commencement of therapy. The results suggest that
      anticonvulsants depress the excitability of human motor pathways in epileptic
      subjects.

PMID- 8874590
TI  - Nasal spray desmopressin treatment of bladder dysfunction in patients with
      multiple sclerosis.
AB  - Bladder dysfunction with increased voiding frequency and incontinence is a common
      problem in patients with multiple sclerosis (MS). In the present study, the
      effect of the synthetic vasopressin analogue, desmopressin, was evaluated on the
      voiding frequency in 26 patients with MS suffering from socially handicapping
      voidings and incontinence problems during daytime. A two-week run-in observation
      period to establish normal voiding patterns was followed by a double-blind,
      placebo-controlled cross-over study with 20 micrograms intranasal desmopressin
      during daily activities. There was a significant decrease in the number of
      voidings during the 6-h period after intranasal intake of desmopressin. Side
      effects were well tolerated and there was no hyponatremia or hypertension
      registered. Intranasal desmopressin is an efficient and well-tolerated treatment
      of voiding problems in patients with MS during daily activities.

PMID- 8874591
TI  - Paroxysmal convergence spasm in multiple sclerosis.
AB  - Paroxysmal phenomena are rare but relatively typical clinical symptoms of
      multiple sclerosis (MS) caused by abnormal excitation in demyelinated plaques. We
      report the case of a 25-year-old woman with ocular convergence spasms as a new
      type of paroxysmal phenomenon in MS. MRI revealed the associated brainstem lesion
      in the region of the medial longitudinal fasciculus. Bromocriptine treatment was
      successful in resolving the paroxysms.

PMID- 8874592
TI  - Visual form agnosia in multiple sclerosis.
AB  - We report a case of multiple sclerosis with visual form agnosia and callosal
      syndromes. Initially, the patient's visual recognition of object form was
      severely disturbed at the perceptual stage, in association with left-sided
      ideomotor apraxia and agraphia. Magnetic resonance imaging showed large white
      matter lesions in the bilateral frontal and occipital lobes, the latter extending
      to the occipitotemporal junction, and widespread corpus callosum lesions. Over
      the course of one year follow-up, neuropsychological examinations indicated that
      the patient's visual recognition defects occurred not only at the early substage
      of form perception, but also at the stage of reproducing the shape of objects
      from visual memory store. The present case suggests that neural connections
      between the striate cortex and occipitotemporal visual areas are crucial for both
      the perceptual and associative stages of visual object recognition.

PMID- 8874593
TI  - Physical activity, trauma, and ALS: a case-control study.
AB  - AIMS: The association of trauma and physical activity with ALS is controversial.
      We explored the relation in a pilot case-control study. MATERIAL AND METHODS: ALS
      patients were selected from a university muscle disease clinic and paired with
      two matched controls: one from the clinic, but having different diseases, and one
      from the community. RESULTS: We found several strong and statistically
      significant differences between ALS cases and the matched controls. These
      included severe head, neck and back injury (OR = 5.3), the frequency of sweating
      in work (OR = 1.6) or leisure activity (also OR = 1.6), and earning a school
      letter (OR = 3.1). Other measures of trauma and activity, while not achieving
      statistical significance (p < 0.05), were in accord with these findings.
      DISCUSSION: Possible explanations include trauma and vigorous exercise
      precipitating ALS; trauma as an early sign of disease; or a third factor
      associated with ALS predisposing to injury. CONCLUSIONS: Severe head, neck, and
      back injury and frequency of sweating both in work and leisure activity showed a
      strong association with ALS. Further study could test narrower and less common
      exposures with greater statistical power.

PMID- 8874594
TI  - Motor neuron disease on Guam: geographic and familial occurrence, 1956-85.
AB  - We investigated the geographic and familial occurrence of motor neuron disease
      (MND) on Guam, and then considered etiologic hypotheses related to cycad use and
      metal intoxication. The research was based on 303 Chamorros from Guam and 3
      Chamorros from other Mariana Islands, all with MND onset on Guam during 1956-85.
      Inarajan and Umatac, two southern districts, each had, for both sexes combined,
      an average incidence rate significantly higher than the corresponding overall
      rate for Guam. Also, for each sex, geographic patterns of incidence were
      significantly related to 1) socioeconomic level (men only), 2) cycasin
      concentrations in cycad flour samples (men and women), 3) iron concentrations in
      water samples (men and women), 4) silicon concentrations in water samples (men
      only), and 5) cobalt and nickel concentrations in soil samples (men and women).
      The MND risk in susceptible sibships was about 7-28 times greater than that in
      the general population. The cycad hypothesis conforms somewhat better than the
      metal intoxication hypothesis with the data presented.

PMID- 8874595
TI  - Autosomal recessive paraparesis with amyotrophy of hands and feet and white
      matter lesions.
AB  - We report two siblings with a hitherto undescribed syndrome of autosomal
      recessive spastic paraparesis accompanied by amyotrophy of hands and feet, and
      mental deterioration. Laboratory tests showed signs of lower motoneuron
      involvement in the four limbs, more accentuated in the distal regions. Brain MR
      showed bilateral symmetrical white matter lesions. We discuss the nosological
      status of this syndrome in relation to other similar forms of "complicated"
      spastic paraparesis.

PMID- 8874596
TI  - Response to thymectomy in South Indian patients with myasthenia gravis.
AB  - AIMS: The rate of remission among patients with myasthenia gravis (MG) following
      thymectomy and the predictors of the outcome have revealed vast variation in
      studies from different geographic regions raising suspicion about the influence
      of ethnic factors. MATERIAL & METHODS: We retrospectively evaluated the outcome
      of 71 South Indian MG patients who were thymectomized between 1987 through 1993
      and analyzed the relationship between clinical and histopathological features and
      postthymectomy outcome. RESULTS: The clinical severity of the disease did not
      differ between the 29 patients with and 42 patients without a thymoma.
      Seventynine percent of our patients responded favourably to thymectomy; without
      additional immunosupression therapy, 52% achieved a near-complete remission. An
      younger age and milder disease correlated with a good outcome. Patients with
      thymoma responded as favourably as those without a thymoma. CONCLUSIONS: The
      postthymectomy response of South Indian MG patients in general did not differ
      from that of Western and Oriental patients.

PMID- 8874597
TI  - Headache of recent onset in adults: a prospective population-based study.
AB  - One hundred consecutive adult patients with headache of recent onset were
      prospectively studied. Every patient was examined by craneal CT scan. Their mean
      age was 46 years (range 17-82). Neurological examination was normal in 80
      patients. Organic headache represented 39% of the entire group, and 26% of them
      had a normal neurological examination. The yield of CT scan in patients with
      headaches and a normal neurological examination was 22.5% (95% IC: 14%-33%); of
      which we encountered the following pathologies: intracranial tumors (13),
      hydrocephalus (2), arachnoid cyst (1), toxoplasmic abscess (1) and parenchymal
      hemorrhage (1). The clinical characteristics of the headache on their own was
      insufficient to rule out the possibility of an intracranial tumor. Neuroimaging
      studies should be performed in all adult patients with non-vascular headache of
      recent onset, and previously headache-free individuals.

PMID- 8874599
TI  - Cognitive function in young Parkinsonian patients.

PMID- 8874598
TI  - Incidence and lifetime prevalence of Bell's palsy in two Sicilian municipalities.
      Sicilian Neuro-Epidemiologic Study (SNES) Group.
AB  - INTRODUCTION: In a door-to-door two-phase survey of common neurologic diseases
      conducted in two Sicilian municipalities, we investigated the incidence and the
      lifetime prevalence of Bell's palsy (BP). MATERIAL & METHODS: During phase I, we
      administered a screening instrument for facial palsy to 11,901 adult persons.
      During phase 2, study neurologists using specified diagnostic criteria evaluated
      those subjects who screened positive. RESULTS: We found 73 subjects who had
      experienced BP during their life. The lifetime prevalence as of November 1, 1987,
      was 642.8 cases per 100,000 population age 15 years and above. The prevalence
      increased with age and was similar in men and women. Eighteen episodes of BP
      occurred in the three years preceding the prevalence day. The average annual
      incidence rate was 52.8 new episodes per 100,000 population age 15 years and
      above. Incidence increased with age. CONCLUSION: Comparison with other incidence
      studies suggests some geographic variability.

PMID- 8874600
TI  - Social skills training for young adolescents: cognitive and performance
      components.
AB  - An assertiveness training curriculum that was an expansion of two previous
      programs with young adolescents (Thompson, Bundy, & Broncheau, 1995; Wise, Bundy,
      Bundy, & Wise, 1991) was presented to 22 fifth graders. Cognitive acquisition and
      retention of the symbolic assertiveness information were measured with multiple
      choice pre- and posttests used in the two prior programs. The performance
      components, including verbal (word choice) and non-verbal (body orientation,
      posture, and gestures) aspects of assertive behavior were measured in pretest and
      posttest role-play situations, with the posttest administered at two levels of
      motivation. When trained students were compared to control groups on the
      cognitive measures, a significant effect for treatment (p < or = .000); a
      significant effect for measures (p < or = .000); and a significant Treatment x
      Measures interaction (p < or = .000) were found. However, the results did not
      show that training facilitated assertiveness on the performance components. When
      trained and control subjects' performance scores were combined, a significant
      effect for measures was found across role-play tests on some of the performance
      measures. Discussion focuses on factors that facilitate adolescents' appropriate
      application of stored symbolic information regarding assertiveness. Suggestions
      are offered for designing programs aimed at developing adolescents' assertive
      behavior in ways that will generalize to their lives beyond the training context.

PMID- 8874601
TI  - The role of cultural norms in the self-esteem and drug use relationship.
AB  - It is widely believed that low self-esteem (SE) is associated with greater
      substance use, although previous research has been unable to support such a
      relationship consistently. The present study used the "social deviance model" to
      investigate whether SE was differentially related to substance use for
      respondents in varying cultural norms. Responses to intensity of tobacco,
      marijuana, alcohol, and drug use, SE, and cultural norm items from over 2,000
      high school and college students failed to support this model.

PMID- 8874602
TI  - Sex differences in the solitary and assaultive fantasies of delinquent and
      nondelinquent adolescents.
AB  - Self-images expressed in response to the Draw-A-Story task were examined for
      differences in gender, age, and delinquency. Subjects included 64 adolescents in
      detention in California and 74 normal controls attending schools in Ohio, New
      York, and Florida; 82 were males (53 delinquents, 29 controls); 56 were females
      (11 delinquents, 45 controls). Their ages ranged between 13 and 17. The first
      analysis evaluated whether gender or delinquency was related to self-image
      scores. No significant differences were found. The second analysis evaluated
      whether the proportions of drawings about solitary subjects or assaultive
      relationships differed depending on gender or delinquency. Significant gender
      differences were found in both solitary and assaultive content. The findings of
      assaultive content were reversed for solitary content. For assaultive content,
      the differences in proportion between male and female control subjects reached
      significance. The difference between male and female delinquents did not reach
      significance. Control males differed significantly from control females, but
      delinquent males did not differ significantly from delinquent females. Solitary
      content also distinguished between delinquent and control groups, as well as
      gender. The gender difference was large in the control group but small in the
      delinquent group. Delinquent female drawings were more like the male drawings of
      both groups. Thus greater gender differences were found among normal adolescents
      than among delinquent adolescents. Implications of the findings for access to
      fantasies and to screen for emotional needs are discussed.

PMID- 8874603
TI  - Consistency in diagnoses for a sample of adolescents at a private psychiatric
      hospital.
AB  - The consistency of psychiatric, psychological, and discharge diagnoses for a
      sample of 97 adolescent inpatients at a private psychiatric and substance abuse
      hospital in the Mid-South was investigated. Percentage agreement between the
      initial evaluations, psychological evaluations, and the exit evaluations ranged
      from 61.7% to 81.6%. Agreement, however, varied by diagnosis. The findings
      revealed relatively strong interrater agreement from the psychiatric diagnosis to
      the discharge evaluation for depression, but interrater agreement for the
      nondepression diagnoses was highly inconsistent. Assessment specialists and
      persons who work with at-risk adolescents are encouraged to evaluate carefully
      the consistency of diagnostic decisions on adolescents with whom they work.

PMID- 8874604
TI  - Adolescent decision making: a broadly based theory and its application to the
      prevention of early pregnancy.
AB  - The purpose of this paper is to present a broadly based theory of adolescent
      decision making including all the necessary components of the subject: cognitive
      development, social and psychological factors, and, perhaps most importantly,
      cultural and societal influences. Previous theories and applications have often
      focused on only one or two aspects. This theory is then applied to the problem of
      prevention of early pregnancy at an inner-city high school. Use of this theory,
      combined with an open-ended data-gathering format made possible some of the
      unexpected findings of this study: most of the young women at this school desire
      their pregnancies; many of them prefer single parenthood to traditional family
      structure; and low academic skills and poverty often result in pregnancy, rather
      than pregnancy causing high school dropouts and a life of poverty. Prevention
      programs will necessarily differ for sexually active adolescents who do and do
      not want pregnancy and for younger versus older adolescents. In designing such
      programs, we need to focus on pregnancy as the problem rather than on adolescent
      sexuality.

PMID- 8874605
TI  - Adolescents' perceptions and experiences of death and grieving.
AB  - Although there is a considerable body of knowledge regarding adolescent grief,
      little research has focused on adolescents' perceptions and experiences of death
      and grief from those who are not currently in the bereavement process. Thirty-two
      adolescents between the ages of 13 to 18 were interviewed about their experiences
      of death and loss. Nineteen of the subjects attended suburban public high school,
      while 13 resided in a facility for adjudicated urban youth. Findings indicated
      that subjects were aware of death by age nine. In this sample, urban adolescents'
      perception of death involved reference to violence (25%) or religion (16.6%) in
      contrast to the suburban youths who referred less frequently to violence (0%) and
      religion (5.3%). The most distasteful aspect of death to the suburban students
      was suffering (31.6%), while it was loss of loved ones to the adjudicated youths
      (25%). Since talking and listening as comforting strategies were used by both
      groups (66.7%), background environment must be considered when examining
      adolescents' experiences and perceptions of death.

PMID- 8874606
TI  - Locus of control, self-concept, and self-esteem among at-risk African-American
      adolescents.
AB  - The purpose of this study was to add to the sparse but growing descriptive data
      on at-risk African-American adolescents along the dimensions of locus of control,
      self-concept, and self-esteem. This study will assist professionals in better
      understanding the boundaries between normal and abnormal psychological profiles
      among adolescents, particularly on instruments which are widely used in
      psychology research and clinical and educational practice. Participants were 117
      students from a large, urban Midwestern city in an ongoing intervention program
      with adolescents who were at-risk of dropping out of school because of academic
      underachievement and whose family's incomes were below the poverty line.
      Descriptive results and comparisons with data on other at-risk samples are
      presented, along with multivariate analyses on the three constructs on the basis
      of gender. This study provides benchmarks for practitioners and researchers in
      interpreting the results of assessments using these instruments.

PMID- 8874607
TI  - Identifying adolescent runaways: the predictive utility of the personality
      inventory for children.
AB  - This study investigated whether runaway behavior could be related to six
      problematic areas. Selected scales of the Personality Inventory for Children,
      representative of the six areas, were hypothesized to discriminate between an
      adolescent runaway group and a control group. Four scales correctly classified
      95.1% of the runaway subjects and 100% of the control subjects with a total
      correct classification rate of 97.52%. It was further hypothesized that the
      runaway group was not significantly different from a known clinical group with
      moderate to severe psychopathology. Results indicated that the runaway group was
      not significantly different except on one scale, Delinquency (DLQ). On the DLQ
      scale the runaway group had a significantly higher mean score than the clinical
      group. Application and recommendations are presented.

PMID- 8874608
TI  - Students who work.
AB  - A study of 1,800 Kentucky high school students revealed that working students
      demonstrate a remarkable diversity of work experience and uses of earnings while
      not differing markedly from nonworking students in school experience. The data,
      both quantitative and qualitative, suggest that conventional wisdom is not
      sufficient to capture fully the current realities of students who work; however,
      unresolved theoretical issues remain.

PMID- 8874609
TI  - The abuse of dextromethorphan-based cough syrup: a pilot study of the community
      of Waynesboro, Pennsylvania.
AB  - Drug abuse has been a national social problem in the United States for decades
      and is often complicated by the emergence of new types of abused drugs or new
      forms of abuse. In the late 1980s, the community of Waynesboro, Pennsylvania
      began to detect behavior among its teenagers that suggested a new form of drug
      abuse and thus a new social problem. The drug was dextromethorphan, used in cough
      syrup-principally Robitussin DM. The form of abuse is often referred to as
      "roboing" or "robo-copping." This paper presents the results of the first phase
      of a comprehensive investigation of this phenomenon in the Waynesboro school
      district. Data from a survey of school personnel indicate that abuse of cough
      syrup (Robitussin or other brands) has increased over the years and is
      increasingly perceived as a problem by the community.

PMID- 8874610
TI  - The collectivistic nature of ethnic identity development among Asian-American
      college students.
AB  - Current theories of ethnic identity oversimplify the development process by
      failing to recognize the malleability of identity within its social context, a
      conceptualization of self that is particularly relevant for Asian-Americans.
      Further, these theories tend to view identity in static, deterministic terms,
      despite social psychology data suggesting that identity is a dynamic ongoing
      process. Data were analyzed from a sample of 87 Asian-American undergraduates,
      using the Ethnic Identity Development Exercise (EIDE). While many theories
      suggest that ethnic identity development is predominantly an internal, intro
      psychic process, our data indicate that Asian-Americans are largely influenced by
      relationships and external forces. In addition, the avoidance of shame was found
      to be a strong motivating factor in determining their ethnic identification.
      Thus, ethnic identification theories must acknowledge the malleable and
      collectivistic nature of ethnic identity development among Asian-Americans. Three
      theoretical frameworks of research on ethnic identity are reviewed and
      summarized: identity formation, social identity, and acculturation.

PMID- 8874611
TI  - Student responses to economic reform in China.
AB  - This paper describes survey research suggesting diverse trends in the behavior
      and attitudes of Chinese students which often conflict with Chinese tradition and
      customs as well as with official Chinese government ideology. The decline of
      personal sacrifice for the social cause and the decline of self discipline are
      examined. Also addressed is what seems to be a rapid change in courtship and
      sexual attitudes among Chinese students, which has developed during the past
      decade. Finally, the varied causes of these changes, most of which are directly
      or indirectly related to China's economic reform program, are discussed.

PMID- 8874612
TI  - Elementary school students' attitudes toward science and their course of studies
      in high school.
AB  - This paper reports on a unique longitudinal study of adolescents which probes the
      relationship between the attitudes of grade 6 male and female students toward
      their school subjects as well as toward adult occupations and their actual course
      of study five years later. The findings indicate that there is almost no
      connection between these attitudes and their course of study in grade 11.
      However, a significant difference was found with regard to the importance grade
      six students assigned to the most scientific occupations and their future
      academic or nonacademic location in the course of study. The major finding is the
      importance of gender differences in their selection of courses of study based on
      the occupations they consider important. These gender differences are explained
      in light of general gender relations in society.

PMID- 8874613
TI  - Black teenage pregnancy in South Africa: some considerations.
AB  - Black teenage pregnancy and sexually transmitted diseases in South Africa have
      reached a threatening level. Accepting that teenage pregnancy is multi
      causational, this article outlines selected consequences. It concludes that
      teenage pregnancy as a social problem needs reexamination in terms of two
      hypotheses: that the pheronomal climate has an impact on prepuberal girls; and
      that teenage pregnancy is nature's way of ensuring the survival of the species.

PMID- 8874614
TI  - Social support and self-esteem in unemployed university graduates.
AB  - The first aim of this study was to examine the relationship between the length of
      time of unemployment and the self-esteem and general life satisfaction of
      university graduates. The second aim was to examine the function of social
      support during the period of unemployment. The sample consisted of 98 unemployed
      university graduates (67 females and 31 males). The measure of self-esteem
      consisted of the adapted Rosenberg scale. The instruments for assessment of
      general life satisfaction and social support were developed by the authors of
      this study. Results showed that length of unemployment, contrary to previous
      findings, was not related to self-esteem and general life satisfaction. Social
      support of the parents and the partner was associated with higher self-esteem of
      unemployed university graduates.

PMID- 8874615
TI  - Guidelines for choosing an "intervention package" for working with adolescent
      girls in distress.
AB  - This article is based on clinical experience and offers principles for
      "tailoring" differential intervention packages for treating girls in distress.
      Profiles of ten types of girls are described and illustrated. Eight major
      features of intervention packages are discussed. Recommendation for matching
      intervention packages to the girls are presented.

PMID- 8874616
TI  - Locus of control in adolescence: a longitudinal study.
AB  - The purpose of this three-year longitudinal study was to investigate the
      development of locus of control in adolescence. Shift and stability of the locus
      of control were examined in an adolescent sample of 84 students: 49 boys and 35
      girls. Locus of control was measured by the Delta questionnaire. Data were
      analyzed using the locus of control as the dependent variable. The independent
      variables measured in relation to the locus of control were sex, type of locus of
      control, and school achievement. Analyses of the longitudinal data revealed
      small, insignificant shifts in the locus of control among both boys and girls
      when they were retested twice: one year and two years later. The male and female
      cohorts, however, diverged between the first, second, and the third testing. The
      girls moved toward the external direction while boys, who were more internal than
      girls at the beginning of the research, became more internal over a one-year
      period, and after the third testing they moved from internal to more external
      locus of control. There was a relationship between type (internal-external) of
      locus of control at the first testing and the changes one year (p < .025) and two
      years (p < .10) later. School achievement was not a significant factor in the
      prediction of locus of control changes. Explanations for these findings are
      suggested. The data and analyses show that adolescence is a period of relative
      stability of locus of control.

PMID- 8874617
TI  - Issues related to the sexual decision-making of inner-city adolescent girls.
AB  - To be effective in reducing the risks of sexual activity in adolescent girls, the
      context of adolescent sexuality needs to be understood. Two focus groups of high
      risk inner-city African-American and Caucasian adolescent girls (15 to 16 years
      of age) were organized to explore issues related to sexual decision-making. The
      transcripts of the groups were reviewed for recurrent themes the girls discussed
      in regard to sexual decision-making, and their views of relationships and images
      of males. Verbatim examples are presented to exemplify each category. These
      adolescents experienced multiple pressures to engage in intercourse at young
      ages, but utilizing the presence of others was described as a helpful means to
      avoid engaging in sexual activities. The lack of mutual trusting relationships
      also was an important aspect for the these girls. Interventions which reduce the
      pressures to engage in sexual behaviours, develop methods for coping with these
      pressures, and facilitate the ability to establish mutual relationships will aid
      the healthy psychosexual development of adolescent girls.

PMID- 8874618
TI  - Adolescents' attitude toward female gender roles: implications for education.
AB  - This exploratory study begins with a number of teachers in a Midwest school
      system being asked if they believed adolescents in general have a more flexible
      attitude toward female gender roles than do older generations. Over 90% answered
      yes. The study then proceeded to examine whether adolescents' attitude toward
      flexible gender roles was indeed more flexible than that of older generations.
      Implications for schooling are then discussed.

PMID- 8874619
TI  - Relationships between college students' perceptions of their family members and
      how they interact with one another.
AB  - In this study 128 college students were surveyed regarding many of their
      perceptions concerning themselves and their family members (i.e., self-concepts,
      evaluations of parents, how they interact with their parents, and how their
      parents interact with each other). Nearly all of the respondents' perceptions of
      these individuals and how they interacted with one another were found to be
      significantly correlated. Such findings suggest that family members need to be
      more attentive to the messages they convey through their actions as well as their
      attitudes, and strive to be as positive as possible if they truly wish to benefit
      all concerned.

PMID- 8874620
TI  - Reduced CD4 cell counts in blood do not reflect CD4 cell depletion in tonsillar
      tissue in asymptomatic HIV-1 infection.
AB  - OBJECTIVE: To investigate whether the loss of CD4 cells seen in peripheral
      circulation of HIV-1-positive individuals reflects a similar depletion of CD4
      cells from lymphoid tissue. DESIGN: CD4 and CD8 cells in tonsillar mononuclear
      cell suspensions were quantified relative to tonsillar B cells, as these were
      thought to remain numerically unchanged in the course of HIV infection. Results
      were related to the CD4 cell counts in blood and to the clinical status of the
      patients. METHODS: Blood samples and tonsillar tissue were obtained from 13 HIV-1
      seropositive individuals and six seronegative controls. B cells and T-cell
      subsets in mononuclear cells were quantified using a three-colour flow cytometry
      protocol. Histological sections were morphologically classified and B-cell areas
      were quantified by morphometry. RESULTS: The B-cell fraction was confirmed to be
      relatively unchanged in asymptomatic HIV-1-seropositive individuals compared with
      controls. The tonsillar CD4 : B-cell ratios in asymptomatic individuals was
      similar to those seen in controls, whereas the CD4 : B-cell ratios in symptomatic
      HIV-1-infected individuals were greatly reduced. The tonsillar CD4 : CD8 cell
      ratios in HIV-1-infected individuals were much lower than those seen in controls,
      in the asymptomatic group due to a considerable expansion of the tonsillar CD8
      cell subset, and in the symptomatic group also due to a loss of CD4 cells.
      CONCLUSIONS: We found no evidence of CD4 cell depletion in tonsillar tissue in
      asymptomatic HIV-1-infected individuals despite low CD4 cell counts in blood.
      Loss of CD4 cells from this lymphoid tissue seems to occur as a late-stage
      phenomenon correlated with the onset of clinical symptoms.

PMID- 8874621
TI  - Factors affecting survival in patients with the acquired immunodeficiency
      syndrome.

PMID- 8874622
TI  - Independent evolution of the env and pol genes of HIV-1 during zidovudine
      therapy.
AB  - OBJECTIVE: To determine the effect that selection for antiviral resistance in the
      HIV-1 pol gene has on the level of variation and pattern of evolution in the V3
      region of env. DESIGN: Proviral genomes obtained from two patients before, during
      and after the termination of zidovudine (ZDV) therapy (approximately 2 years)
      were amplified and sequenced in pol and env, and the evolution of the V3
      hypervariable region compared with that of the reverse transcriptase domain of
      pol. METHODS: Gene fragments were polymerase chain reaction-amplified from
      patients' peripheral blood mononuclear cells. Nucleotide sequencing was carried
      out using T7 DNA polymerase and dye-labelled terminators on an automated DNA
      sequencer. Sequences were analysed using maximum likelihood phylogenetic
      techniques. RESULTS: Both patients showed multiple resistance-associated
      mutations after 1 year of ZDV therapy. Sequence diversity in V3 showed no
      reduction during the period of treatment. Substantial change continued to occur
      in this region and multiple lineages were present in both patients, in contrast
      to the single lineage observed in the pol gene of one (patient 74), a difference
      confirmed by likelihood ratio tests. CONCLUSIONS: There is no evidence from this
      study that selection due to antivirals has any significant impact on the
      evolution of the env gene. The independence in the evolution of these genes
      implies that recombination was occurring between the two genes during the study
      period. Such independent evolution should be allowed for in developing strategies
      for HIV therapy involving multiple target genes.

PMID- 8874623
TI  - Identification of multiple HIV-1 cytotoxic T-cell epitopes presented by human
      leukocyte antigen B35 molecules.
AB  - OBJECTIVE: To identify HIV-1 cytotoxic T lymphocyte (CTL) epitopes presented by
      human leukocyte antigen (HLA)-B35 molecules that are associated with the
      accelerated progression of AIDS using a reverse immunogenetic approach. METHODS:
      8-mer to 11-mer sequences carrying two anchor residues at position 2 and the
      carboxy-terminus were selected from HIV-1SF2 strain. Sixty-four peptides matched
      to these sequences were synthesized and tested by a peptide binding assay using
      RMA-S-B*3501 cells. Peripheral blood lymphocytes (PBL) from two HIV-1-infected
      donors carrying HLA-B35 were stimulated once-weekly with each HLA-B*3501 binding
      peptide. The CTL activity of the cultured cells for the HLA-B35-positive target
      cells loaded with the corresponding peptides was examined after the second and
      fourth stimulation. Furthermore, the CTL activity of the cultured cells
      possessing HLA-B*3501-restricted HIV-1 peptide-specific CTL activity were
      examined for the HLA-B*3501-positive target cells infected with the recombinant
      vaccinia virus containing corresponding HIV-1 gene. RESULTS: HIV-1 peptide
      specific HLA-B*3501-restricted CTL was induced in PBL of HIV-1 infected donors by
      in vitro stimulation with 11 out of 27 HLA-B*3501-binding HIV-1 peptides. The
      specific CTL induced with 10 peptides killed the cells infected with recombinant
      vaccinia virus expressing the corresponding HIV-1 proteins. Out of these HIV-1
      peptide epitopes, two epitopes were also presented by HLA-B51 molecules.
      CONCLUSION: In addition to the four HLA-B35-restricted HIV-1 CTL epitopes that
      have been previously reported, nine HLA-B35-restricted HIV-1 CTL epitopes were
      identified in the present study. These multiple epitopes will be useful in
      studies for immunopathogenesis of AIDS.

PMID- 8874624
TI  - Heat-mediated immune complex dissociation and enzyme-linked immunosorbent assay
      signal amplification render p24 antigen detection in plasma as sensitive as HIV-1
      RNA detection by polymerase chain reaction.
AB  - OBJECTIVE: To compare heat denaturation and acidification as immune complex
      dissociation (ICD) methods in adult HIV-1 infection and to increase the
      sensitivity by a signal-amplification-boosted HIV-1 p24 antigen enzyme-linked
      immunosorbent assay (ELISA). DESIGN: Prospective and retrospective blinded study
      of paired serum and plasma samples from 245 patients (112 of class A, 66 of B, 67
      of C of the Centers for Disease Control and Prevention 1993 classification).
      METHODS: Plasma and sera were prospectively tested for antigen by ELISA using
      native, acidified, or heat-denatured material. Retrospective tests included batch
      analysis of heat-denatured samples for antigen by the signal-amplification
      boosted ELISA and for viral RNA. RESULTS: With serum, native antigen was reactive
      in 26.5%. Acidification increased the rate to 53.1% (P < or = 0.0001), but was
      inefficient at a CD4+ count > or = 500 x 10(6)/l. Heat denaturation further
      elevated the rate to 67.8% (P < or = 0.0007) and the use of plasma to 78.0% (P <
      or = 0.008). The boosted ELISA, performed with plasma samples diluted 1 :6, which
      eliminated the problem of heat-induced sample coagulation, was confirmed positive
      in 89.5% of serum and 97.8% of plasma samples. RNA was detected in 95.7%.
      CONCLUSION: Heat-mediated ICD combined with a signal-amplification-boosted ELISA
      detects HIV-1 expression as sensitively as a polymerase chain reaction kit for
      viral RNA, but at only a fraction of the cost. The procedure uses a 50
      microliters plasma sample and should be fully automatable.

PMID- 8874625
TI  - Serological and polymerase chain reaction-based analysis of aqueous humour
      samples in patients with AIDS and necrotizing retinitis.
AB  - OBJECTIVE: To evaluate the measurement of intraocular antibody production and
      detection of DNA by the polymerase chain reaction (PCR) for diagnosis of the
      causative microorganism in patients with AIDS and necrotizing retinitis. METHODS:
      Paired serum and aqueous humour samples obtained from 28 patients with AIDS and
      necrotizing retinitis, seen between January 1987 and March 1992, were analysed
      for intraocular antibody production against cytomegalovirus (CMV), varicella
      zoster virus, herpes simplex virus, Epstein-Barr virus, and Toxoplasma gondii.
      Specific antibody titres in the inflamed eye and in the circulation were related
      to total immunoglobulin G content in the aqueous humour and serum. In addition,
      PCR analysis was performed in 15 samples. Results were compared to the final
      diagnosis, which was based on the subsequent clinical course. Results were also
      related to parameters describing the immune state of the patients: CD4 count,
      time between diagnosis of an AIDS-defining illness and retinitis, and time of
      survival following the diagnosis of retinitis. RESULTS: In 11 (39%) out of 28
      patients we found local intraocular antibody production which correlated with the
      final diagnosis (one out of two cases with acute retinal necrosis, three out of
      five cases with toxoplasma retinitis, and eight out of 21 patients with CMV
      retinitis). In all 13 patients with CMV retinitis PCR analysis detected CMV DNA.
      In one patient with the clinical diagnosis of Toxoplasma retinitis, Toxoplasma
      DNA could be determined, whereas in the same sample CMV DNA was also found. In
      yet another patient with Toxoplasma retinitis only CMV DNA could be detected. A
      relationship between results of local antibody determination with either CD4
      counts, or the time interval between AIDS-defining illness and retinitis, or
      survival time after diagnosis of retinitis could not be established. CD4 counts
      were higher than 50 x 10(6)/l in eight out of 19 patients with CMV retinitis. No
      complications of paracentesis were seen. CONCLUSIONS: Detection of intraocular
      antibody production and PCR analysis are quick and safe procedures and helpful
      tools for diagnosis of the involved pathogen in AIDS patients with a necrotizing
      retinitis. Negative results of local antibody production, even in the presence of
      detectable viral DNA, could not be related to the parameters of a more
      deteriorated immune status of these patients.

PMID- 8874626
TI  - Anti-herpesvirus treatment and risk of Kaposi's sarcoma in HIV infection. Royal
      Free/Chelsea and Westminster Hospitals Collaborative Group.
AB  - OBJECTIVE: With the recent identification of a new herpesvirus in patients with
      Kaposi's sarcoma (human herpesvirus-8 or Kaposi's sarcoma-associated
      herpesvirus), there have been several reports on the use of anti-herpesvirus
      therapy (foscarnet, ganciclovir and aciclovir) and risk of developing Kaposi's
      sarcoma. We therefore investigated the association between use of anti
      herpesvirus drugs and Kaposi's sarcoma in a large unselected group of patients
      with AIDS. PATIENTS AND METHODS: We studied a group of HIV-positive patients at
      the Chelsea and Westminster Hospital, for whom details on all AIDS-defining
      diagnoses made during follow-up, treatment and regular CD4 counts were available.
      Cox proportional hazards models with time-dependant covariates were used to
      assess the association between treatment with aciclovir, foscarnet and
      ganciclovir and risk of Kaposi's sarcoma. RESULTS: A total of 3688 patients have
      been followed up for a median period of 4.2 years, during which time 598 patients
      (16.2%) developed Kaposi's sarcoma. After adjustments for sex, exposure category,
      age, treatment with antiretrovirals or Pneumocystis carinii pneumonia
      prophylaxis, the development of AIDS-defining conditions (including separate
      adjustment for the development of cytomegalovirus and herpes simplex virus) and
      CD4 count, there was a decreased risk of developing Kaposi's sarcoma with
      foscarnet [relative hazard (RH), 0.38; 95% confidence interval (CI), 0.15-0.95; P
      = 0.038] and with ganciclovir (RH, 0.39; 95% CI, 0.19-0.84; P = 0.015), but not
      with aciclovir (RH, 1.10; 95% CI, 0.88-1.38; P = 0.40). CONCLUSIONS: These
      results suggest that both foscarnet and ganciclovir may have some activity in
      preventing the occurrence of Kaposi's sarcoma, but that aciclovir has no benefit.
      Further studies of the effect of these drugs on the risk of Kaposi's sarcoma is
      warranted.

PMID- 8874627
TI  - Atovaquone as long-term suppressive therapy for toxoplasmic encephalitis in
      patients with AIDS and multiple drug intolerance. Atovaquone Expanded Access
      Group.
AB  - OBJECTIVE: To evaluate the efficacy and tolerance of atovaquone used as long-term
      maintenance therapy in patients with toxoplasmic encephalitis and intolerant of
      conventional anti-Toxoplasma therapies. DESIGN: Uncontrolled open-label study of
      atovaquone given through an expanded access programme; statistical analysis was
      performed on an intent-to-treat basis. PATIENTS: Sixty-five patients intolerant
      of conventional toxoplasmic encephalitis therapies-pyrimethamine, sulphadiazine
      or clindamycin-received atovaquone as maintenance therapy after resolution of an
      acute episode of toxoplasmic encephalitis. Patients were clinically and
      neurologically evaluated monthly. Toxoplasmic encephalitis relapse was defined as
      the occurrence of neurological abnormalities, except in the case of a proven
      alternative diagnosis. RESULTS: Sixty-five patients were treated with atovaquone
      750 mg four times daily and followed up for a mean period of 1 year. Mean CD4
      lymphocytes count was 29 x 10(6)/l. Prior to starting atovaquone, patients had
      experienced a total of 129 episodes of intolerance to conventional anti
      Toxoplasma drugs. Atovaquone was used as a single anti-toxoplasmic agent in 75%
      of the cases. Seventeen patients (26%) experienced a toxoplasmic encephalitis
      relapse. Sixty-three patients (97%) were able to tolerate and continued taking
      atovaquone. Two patients had to discontinue therapy because of side-effects. In a
      multivariate analysis, only the duration of pyrimethamine-sulphadiazine therapy
      during the acute therapy phase of toxoplasmic encephalitis was significantly
      associated with a decreased risk of toxoplasmic encephalitis relapse during
      maintenance therapy [relative risk, 0.64 for each week of pyrimethamine
      sulphadiazine; 95% confidence interval (CI), 0.42-0.96; P = 0.03]. The survival
      probability was 70% at 1 year after the episode of toxoplasmic encephalitis (95%
      CI, 57-83). CONCLUSION: These results suggest that atovaquone is a well-tolerated
      alternative anti-Toxoplasma treatment for maintenance therapy in patients who are
      intolerant to conventional anti-Toxoplasma drugs.

PMID- 8874628
TI  - Relationship between foscarnet exposure, baseline cytomegalovirus (CMV) blood
      culture and the time to progression of CMV retinitis in HIV-positive patients.
AB  - OBJECTIVE: To determine some of the factors influencing the time to progression
      of cytomegalovirus (CMV) retinitis among HIV-infected patients being treated with
      foscarnet. DESIGN: A retrospective analysis of two open-label Phase I/II studies
      in multiple university hospitals. Patients were studied in both inpatient and
      outpatient settings. PATIENTS: Of the patients in the databases examined, 31 had
      adequate pharmacokinetic information and 29 had information on outcome and the
      other patient covariates. INTERVENTION: After induction therapy with foscarnet at
      a dose of 60 mg/kg three times daily was completed, patients had maintenance
      therapy with 60-120 mg/kg foscarnet once daily. Doses were subsequently adjusted
      for changed estimated creatinine clearance. MEASUREMENTS: The measured endpoint
      was time to progression of CMV retinitis. The independent variables examined to
      determine influence on time to progression included mean peak foscarnet
      concentration, mean area under the concentration-time curve (AUC) for foscarnet,
      the positive or negative outcome of a baseline blood culture for CMV, the initial
      CD4 cell count for a patient and the peak CD4 cell count observed during
      maintenance therapy. RESULTS: A wide range (-10-fold) of foscarnet AUC was
      observed, even though only a fourfold dose range was employed, and doses were
      altered for changing estimated creatinine clearance. In a multivariate Cox model,
      only AUC and the status of the baseline CMV blood culture significantly affected
      the time to progression of the retinitis. CONCLUSION: The AUC produced by a dose
      of foscarnet has a wide interindividual range. The AUC of foscarnet significantly
      altered time to progression of the retinitis. However, patients with positive
      baseline CMV blood cultures had a significantly more shallow dose-response curve.
      This indicates that the added risk of nephrotoxicity which is present with
      aggressive foscarnet dosing might be best borne by the subgroup of patients with
      a positive CMV blood culture at baseline.

PMID- 8874629
TI  - The association between cigarette smoking and selected HIV-related medical
      conditions.
AB  - OBJECTIVE: To clarify the effect of cigarette smoking on the development of
      conditions associated with HIV infection. DESIGN: Prospective and retrospective
      cohort study, with interview and examination twice a year since 1988. METHODS:
      Data on 516 HIV-infected men from cohorts of homosexual and bisexual men in San
      Francisco, Denver and Chicago, who were repeatedly interviewed and examined
      between 1988 and 1992, were analysed. After excluding men who did not have well
      defined dates of seroconversion and those who were classified as ex- or
      intermittent smokers, 232 men remained for analysis: 106 were smokers and 126
      were non-smokers. Univariate and Kaplan-Meier survival analyses were performed to
      assess the relationship between cigarette smoking and loss of CD4+ T-lymphocytes,
      diagnosis of any AIDS-defining illness, and specific diagnosis of Kaposi's
      sarcoma, Pneumocystis carinii pneumonia (PCP), oral candidiasis, hairy
      leukoplakia, and community-acquired pneumonia. RESULTS: By univariate analyses,
      cigarette smoking was not associated with clinical AIDS, loss of CD4+ cells,
      Kaposi's sarcoma or PCP, but was significantly associated with oral candidiasis
      [relative risk (RR), 1.32; 95% confidence interval (CI), 1.02-1.70], hairy
      leukoplakia (RR, 1.51; 95% CI, 1.15-1.99), and community-acquired pneumonia (RR,
      2.62; 95% CI, 1.30-5.27). Dose-response effect was also evident for these three
      conditions (all P < 0.01). Kaplan-Meier survival analysis indicated no
      association between cigarette smoking and time of progression to clinical AIDS,
      Kaposi's sarcoma (KS), or PCP (P = 0.62, 0.54 and 0.11, respectively) but showed
      that cigarette smokers developed oral candidiasis, hairy leukoplakia, and
      pneumonia more quickly than non-smokers (P = 0.031, 0.006 and 0.009,
      respectively). CONCLUSIONS: Cigarette smoking was not associated with an
      increased likelihood or rate of developing KS, PCP or AIDS, but was associated
      with developing community-acquired pneumonia, oral candidiasis, and hairy
      leukoplakia in these HIV-infected men.

PMID- 8874630
TI  - Rapid progression of HIV disease in children with cytomegalovirus DNAemia.
AB  - OBJECTIVE: In HIV-1-infected children, active cytomegalovirus (CMV) infection can
      cause severe clinical manifestations and accelerate progression of HIV disease.
      However, sufficient quantities of blood samples may not be available either for
      culture or detection of CMV DNA or antigens in white blood cells. The aim of this
      study was to investigate the diagnostic and prognostic significance of detecting
      CMV DNA in serum samples from HIV-1-infected children. DESIGN: Sera from 55
      children (18 boys), aged 2-130 months (mean, 49.8 months), with perinatal HIV-1
      infection and clinical manifestations attributable to CMV infection were tested
      for CMV DNA by nested polymerase chain reaction and for class-specific CMV
      antibodies [immunoglobulin (Ig) G, IgA, IgM] by enzyme-linked immunosorbent
      assay. The children were followed up for 2 days to 59 months (mean, 25.5 months).
      RESULTS: CMV infection was demonstrated in 43 children (74.5%), 18 of whom (42%)
      were positive for CMV DNA. During the follow-up, 13 children with CMV infection
      (30.2%) died, including 11 (84.6%) who were positive for CMV DNAemia just before
      death. Of these children, seven died soon after hospitalization without antiviral
      treatment, and four died despite therapy with ganciclovir or foscarnet. Post
      mortem CMV inclusions were revealed in seven out of eight children who underwent
      autopsy. The two other children who died also had progressive CMV disease and
      received ganciclovir until death. In comparison with CMV-seropositive children
      without CMV DNAemia, children with CMV DNAemia showed significantly shorter mean
      survival time (42.5 versus 60 months; P < 0.01), lower final CD4+ T-cell count
      (218 versus 499 x 10(6)/1; P < 0.01) and higher mortality rate (P < 0.0001).
      CONCLUSIONS: The detection of CMV DNA in serum is of value for diagnosis of
      active CMV infection in HIV-1-positive children, and CMV DNAemia is a good
      prognostic indicator of severe outcome of HIV disease.

PMID- 8874631
TI  - Risk factor analysis and serological diagnosis of HIV-1/HIV-2 infection in a
      Brazilian blood donor population: validation of the World Health Organization
      strategy for HIV testing.
AB  - OBJECTIVE: To determine the relative prevalence of HIV-1 and HIV-2 and to
      evaluate the World Health Organization testing strategy for HIV diagnosis in a
      low-risk population in Brazil. In addition, to assess risk factors for HIV
      infection. DESIGN: Sera obtained from 9885 consecutive blood donors were screened
      in parallel by two HIV enzyme-linked immunosorbent assays (ELISA) with different
      antigen composition and test principles (Ortho HIV-1 and Wellcozyme HIV-1/2).
      Samples reactive to either ELISA were submitted to a Western blot assay and to a
      rapid HIV-1/2 ELISA (Sero-Immuno Diagnostics). An ELISA test with specific HIV
      1/HIV-2-derived synthetic peptide was used to discriminate between samples
      reactive on the Wellcozyme HIV-1/2 assay. Demographic and serological data were
      used to address risk factors for HIV infection. RESULTS: All the 28 Western blot
      confirmed positive samples were reactive in both Ortho HIV-1 and Wellcozyme HIV
      1/2 assays (sensitivity, 100%). The Wellcozyme HIV-1/2 specificity (99.9%) was
      higher than Ortho HIV-1 (99.5%). If sample reactivity to both tests was
      considered positive, the sensitivity and specificity of the screening would be
      100%. However, further analysis with a third rapid HIV-1/2 ELISA reduced both the
      sensitivity and the specificity of the sequential testing strategy.
      Discrimination between HIV-1 and HIV-2 showed evidence for the presence of HIV-1
      only. Finally, in the group aged 18-35 years, the presence of serological markers
      of hepatitis C virus and hepatitis B virus infections and the elevated levels of
      beta 2-microglobulin were variables associated with the identification of HIV-1
      seropositive blood donors. CONCLUSION: In a low-risk population, application of
      two high quality ELISA tests with different antigens and test principles can
      replace the use of the Western blot. In addition to the cost being reduced by 10
      16%, a rapid diagnosis and the absence of indeterminate Western blot results
      confer an advantage to this strategy.

PMID- 8874632
TI  - The epidemiology of HIV-1 infection in Peru, 1986-1990.
AB  - OBJECTIVE: To determine the extent of the HIV-1 epidemic in Peru. DESIGN: Part of
      a national serosurvey in Peru. METHODS: Between January 1986 and December 1990,
      140,976 serum samples were tested for HIV-1 antibody. RESULTS: HIV-1 antibody was
      found in a high percentage of serum samples provided by 4300 homosexual men
      (26%), 2204 male sexually transmitted disease patients (10%), 145 drug users
      (13%), 269 hemophiliacs (10%), and 146 unlicensed female prostitutes (10%). In
      addition, the prevalence of HIV-1 infection increased substantially among these
      groups between the beginning and end of the survey period. A low but rising
      prevalence of HIV-1 antibody was found during this period among serum samples
      provided by 83,526 blood donors and 11,101 military personnel:total period
      prevalence, 0.25 and 0.32%, respectively. CONCLUSION: These data indicate that
      HIV-1 infection is epidemic in Peru among groups at high risk of sexually and
      parenterally transmitted diseases, and that the risk of infection appears to be
      low but possibly increasing among the general population.

PMID- 8874633
TI  - Racial differences in rate of CD4 decline in HIV-1-infected homosexual men.
AB  - OBJECTIVE: To determine whether racial differences exist in the rate of CD4
      lymphocyte decline in HIV-1-infected homosexual men. DESIGN: Prospective cohort
      study. STUDY POPULATION: Non-Hispanic white (n = 321) and black (n = 102) HIV-1
      seropositive homosexual and bisexual men were recruited from the
      Baltimore/Washington, DC metropolitan areas between 1984-1985 and 1987-1990, and
      evaluated semiannually. MAIN MEASUREMENTS: Changes in CD4 lymphocyte count and
      CD4 percentage over time were analysed using linear regression methods for the
      271 white and 69 black participants who had at least four semiannual CD4
      lymphocyte measurements. RESULTS: Rate of decline in CD4 lymphocyte count over 6
      months was much slower among black than white seroprevalent men at all levels of
      baseline CD4 count (baseline 201-400 x 10(6)/l: + 0.24 versus -17.7 x 10(6)/l;
      401-600 x 10(6)/l: -11.3 versus -23.9 x 10(6)/l; 601-800 x 10(6)/l: -15.1 versus 
      35.2 x 10(6)/l; > 800 x 10(6)/l: -4.3 versus -42.7 x 10(6)/l for black versus
      white, respectively), although this was only statistically significant for the
      lowest and highest strata of baseline CD4 count. These racial differences
      persisted after adjustment for recruitment period (1984-1985 or 1987-1990),
      follow-up duration, age and zidovudine therapy or Pneumocystis carinii pneumonia
      prophylaxis. Similar findings were observed among the 70 white and 11 black
      seroconverters. Black participants were also less likely than a subgroup of white
      participants matched on baseline CD4 lymphocyte count to be HIV-1 p24 antigen
      positive. However, after acid dissociation of samples initially p24 antigen
      negative, there were no significant differences in the prevalence of p24
      antigenemia at enrollment or after 1 year of follow-up. CONCLUSIONS: This
      analysis suggests a more gradual decline in CD4 lymphocyte count among black than
      white Americans. The clinical significance of and reasons for this are unclear,
      but the lower prevalence of p24 antigenemia due to immune complexing among black
      Americans suggests that racial differences in the immune response to HIV may
      exist. Additional studies are needed to validate these findings in a larger
      cohort of non-whites, and to assess their relationship with other measures of
      cell-mediated immune function.

PMID- 8874634
TI  - Estimated rate of HIV-1-infectious but seronegative blood donations in Bangkok,
      Thailand.
AB  - OBJECTIVES: To determine HIV seroprevalence and incidence among various blood
      donor types, and to estimate the rate of window-period blood donations. DESIGN:
      Retrospective cohort from computerized donor records. METHODS: Records were
      analysed from all 60,483 donors (contributing 97,464 donor units) at a public
      university teaching hospital blood bank in Bangkok, Thailand, from 1 January 1990
      to 30 June 1993. Annual HIV incidence among 14,482 repeat donors who were HIV
      seronegative on their first donation was calculated assuming equal probability of
      seroconversion between last seronegative and first seropositive donations. To
      estimate the probability of window-period donations, we assumed that the time
      from HIV infectivity to onset of detectable antibody was 45 days. RESULTS: In
      1990, HIV incidence calculated for all repeat donors was 307 per 100,000 person
      years; the probability of a window-period donation was 38 in 100,000 donations or
      one in 2644 donations. During 1991-1993, this probability decreased by one-half.
      However, one-time donors were more than twice as likely as repeat donors to be
      HIV-1-seropositive. CONCLUSIONS: The rate of HIV window-period blood donations
      among Thai repeat donors was relatively high compared with that in developed
      countries and was probably even higher among one-time donors. Improved donor
      deferral criteria are needed in Thailand.

PMID- 8874635
TI  - Behavioral effects of receiving HIV test results among injecting drug users in
      Puerto Rico.
AB  - OBJECTIVES: To examine the influence of knowledge of HIV serostatus on changes in
      risk behaviors among injecting drug users (IDU). PROCEDURES: IDU were recruited
      through sampling conducted at street drug-selling areas. Of 374 participants,
      88.8% consented to be HIV tested and returned for their test results, and 73.5%
      were relocated and interviewed 6 months later. RESULTS: Of the 176 IDU who
      reported a seronegative test result prior to baseline, 29 tested seropositive at
      baseline. No significant differences were found between HIV-positive and HIV
      negative IDU in needle risk behaviors. HIV-positive IDU were significantly less
      likely to report being sexually active [odds ratio (OR), 0.41 : 95% confidence
      interval (CI), 0.22-0.75] and more likely to use condoms during vaginal (OR,
      4.43; 95% CI, 1.48-13.29) and oral sex (OR, 6.67; 95% CI, 1.42-31.33).
      CONCLUSION: The findings of this study show the importance of encouraging IDU to
      undergo periodic retesting. HIV testing could have an important role in reducing
      heterosexual transmission from IDU.

PMID- 8874636
TI  - Hepatitis B vaccination in HIV-1-infected children: double efficacy doubling the
      paediatric dose.

PMID- 8874637
TI  - Splenectomy and prognosis of HIV infection. Group d'Epidemiologie Clinique du
      SIDA en Aquitaine (GECSA)

PMID- 8874638
TI  - Antimony/interferon-gamma combination in the treatment of visceral leishmaniasis
      in AIDS.

PMID- 8874639
TI  - Ocular and neurological complications of varicella zoster virus infection in a
      patient with AIDS.

PMID- 8874640
TI  - Rapid epifluorescent technique to detect microsporidia.

PMID- 8874641
TI  - Passive immunotherapy for rotavirus-induced diarrhoea in children with HIV
      infection.

PMID- 8874642
TI  - Presence of Chlamydia pneumoniae strain TWAR in bronchial secretions collected
      from HIV-positive and negative patients: preliminary data.

PMID- 8874643
TI  - Disseminated papular eruption caused by Serratia marcescens: a new cutaneous
      manifestation in HIV-positive patients.

PMID- 8874644
TI  - Confronting the emerging HIV epidemic in Vietnam: social context and preliminary
      data on physician preparedness.

PMID- 8874645
TI  - Sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period. The
      New York City Perinatal HIV Transmission Collaborative Study Group.

PMID- 8874646
TI  - Developing a cost-effective media campaign addressing unprotected anal sex among
      gay men.
AB  - This paper describes the development and implementation of the Stella Seattle
      campaign, a media campaign targeting men who have unprotected anal sex with other
      men. Stella Seattle utilizes a serial cartoon strip format. Scenarios and
      characters in the strip are derived from local formative research on factors
      associated with unprotected anal sex in men who have sex with men, including
      depression, isolation, misinformation, and normative behavior. Weekly strips
      illustrating the struggles and hopes of gay men who are practicing unprotected
      anal sex are distributed in postcard form throughout the gay community and are
      placed in two weekly newspapers. Surveys conducted in the gay community and at an
      HIV test site indicate that 35% to 45% of men have seen Stella, and of these men
      about half have discussed it with their friends.

PMID- 8874647
TI  - Cognitive and emotional assessments of perceived risk for HIV among unmarried
      heterosexuals.
AB  - We examined perceived risk of contracting HIV using assessments of likelihood and
      worry in a probability sample of unmarried heterosexuals. Perceptions of the
      likelihood of contracting HIV and worry about HIV were only modestly correlated
      (r = .23), suggesting that they are different constructs. Far more respondents
      expressed worry (43%) than expressed the belief that they were at risk for HIV
      (9%). A significant proportion of the sample reported experiences that may have
      placed them at risk for HIV transmission. Demographic and psychosocial correlates
      of perceived likelihood and worry were examined in separate multivariate logistic
      analyses. Misconceptions about HIV transmission, a history of injection-drug
      using sexual partners, and less education were associated with higher perceived
      likelihood of contracting HIV. Misconceptions, having multiple sexual partners in
      the past year, and a history of sexually transmitted diseases (STDs) were
      associated with high worry about HIV. Implications of the findings for correcting
      HIV-related misconceptions are discussed.

PMID- 8874648
TI  - Self-reported risk factors for AIDS among homeless youth.
AB  - This study assessed HIV risk behaviors in a sample of homeless youth in a large
      urban area and examined factors associated with these behaviors. Self-reported
      behaviors were assessed via interviews with 196 homeless youth in Chicago in all
      10 urban shelters serving this group and in 5 street locations. Overall, 83.7%
      reported at least one of these risk factors: multiple sex partners; high-risk
      partners; inconsistent condom use; history of sexually transmitted disease; anal
      sex; prostitution; and/or intravenous drug use. An index of these behaviors was
      associated with being male, having unmet personal needs, being interviewed in
      street locations, and having a history of sexual abuse. Findings suggest that
      strategies that may decrease risk behaviors among homeless youth include the
      elimination of their need to rely on illicit activities for income, provision of
      basic needs, education regarding existing services, increased outreach efforts,
      and early identification of and protection from childhood sexual abuse.

PMID- 8874649
TI  - Assessing reading level of drug users for HIV and AIDS prevention purposes.
AB  - Using the short form of the Woodcock Reading Mastery Test-Revised and the reading
      subtest of the Wide Range Achievement Test-Revised, the reading abilities of 284
      male and 128 female drug users from five sites across the United States were
      evaluated. All subjects were participants in a National Institute on Drug Abuse
      HIV/AIDS prevention project aimed at intravenous drug users and cocaine smokers.
      Results revealed differences in reading abilities among ethnic groups with Native
      and white subjects having significantly higher reading levels than Hispanic and
      black subjects. Significant site differences were revealed, with mean grade
      equivalent scores ranging from 2.7 to 10.1 grades. Across all subjects, the
      average grade equivalent reading level was 5.8 to 7.7, indicating that the
      subjects read below the level of 81.5% to 93% of the general population. We
      provide implications for development of educational materials that are accessible
      for this population.

PMID- 8874650
TI  - HIV-related concerns and behaviors among Hispanic women.
AB  - Hispanic women whose sexual partners have other sexual partners may be at risk
      for HIV. A structured interview was administered to 106 Dominican and Puerto
      Rican women who reported that they knew or suspected that their partner had other
      partners. A subsample participated in qualitative interviews. The study assessed
      concern about HIV and predictors of condom use. The majority of women reported
      that they worried about getting HIV and almost half had been HIV-tested. Most of
      the women discussed HIV/AIDS concerns with their partners, and one-third reported
      some condom use. Predictors of condom use were: born in the Dominican
      Republic/Puerto Rico, having talked with their partner about being tested, and
      belief that he used condoms with others. Although the women were concerned about
      HIV, condom use was infrequent. Results suggested methods to address this
      discrepancy: introducing condoms early in the relationship, developing women
      controlled methods, and directly influencing men's behavior.

PMID- 8874651
TI  - Needs assessment for an urban native HIV and AIDS prevention program.
AB  - At the request of Native community-based organizations in Montreal, a needs
      assessment for an HIV and AIDS education and prevention program for urban Natives
      was initiated. A five-session focus group concerning HIV and AIDS was attended by
      nine Native persons over a 2-month period. Data was collected using the
      guidelines of the HIV/AIDS Rapid Anthropological Assessment Procedures (AIDS RAP)
      developed by the Social and Behavioural Research Unit of the World Health
      Organization's Global Programme on AIDS. We followed these up with in-depth
      semistructured interviews with five different members of the Montreal Native
      community. The data were reviewed by a steering committee to ensure validity.
      Findings highlight the potential explosive route of transmission of HIV along
      networks of sexual interaction between persons in urban areas and then to rural
      partners. Maintaining control over the AIDS program planning within the community
      permits issues such as traditional values and healing practices to be discussed
      and taken into account.

PMID- 8874652
TI  - Prevention implications of AIDS discourses among South African women.
AB  - Social constructionist and feminist analyses have done much to extend the
      understanding of AIDS beyond the biomedical to include social accounts of the
      constitution of AIDS knowledge and meanings. However, these frameworks have not
      translated easily into realistic responses to the paradox of women being seen as
      responsible for HIV prevention, while they lack the power to implement safe sex
      behavior. This study explores the range and interplay of discursive themes which
      South African women drew on regarding AIDS and identifies constraints and
      opportunities for realistic prevention. The research involved 14 focus group
      discussions with women. Two main interpretative repertoires regarding AIDS were
      identified from the texts: one concerning the medicalization and the other the
      stigmatization of the disease. Although these representations were not
      unchallenged, the pervasive sense was of denial of own risk, fear, and fatalism.
      However, the analysis highlighted the complexity of issues to be faced in
      developing effective prevention initiatives.

PMID- 8874653
TI  - Assigning new meanings to traditional literature: illustrations for HIV
      educators.
AB  - Folk literature (folktales, fairy tales, and myths) has always had a
      psychological and sociological impact on humans. Parents and educators have been
      using stories from folk literature for generations to convey significant ideas
      and cultural values. With HIV being a major health concern, there is a need to
      establish diverse approaches to health education. Literature as a genre, and
      storytelling as an art form, can be used to help forward public health messages.
      Examples of storytelling in educational settings are provided.

PMID- 8874654
TI  - "Sensitivity to electricity"--a new environmental epidemic.

PMID- 8874655
TI  - Enhancement of basophil histamine release by interleukin-3: reduced effect in
      atopic subjects.
AB  - The inducing and enhancing effects of interleukin-3 (IL-3) on basophil histamine
      release in patients with respiratory allergy (n = 28) and in normal subjects (n =
      22) were compared. Leukocyte suspensions, prepared by dextran sedimentation, were
      stimulated with anti-IgE (1/5000), N-formyl-methionyl-leucyl-phenylalanine (FMLP,
      1 microM), and IL-3 (0.1-10 ng/ml), and histamine concentration was measured by
      an automated fluorometric method. A trend toward higher histamine release after
      challenge with anti-IgE, FMLP, and IL-3 was found in atopic subjects.
      Preincubation of basophils with IL-3 resulted in a dose-dependent increase of
      anti-IgE- and FMLP-induced histamine release, with a more marked effect in
      nonatopic than in atopic subjects. Mean net enhancement of anti-IgE-induced
      histamine release by 10 ng/ml IL-3 was 2.5 +/- 5% in atopic subjects and 29.6 +/-
      4.2% in nonatopic subjects (P < 0.001). The enhancement of FMLP-induced histamine
      release by IL-3 was 10.3 +/- 3.9% in atopic patients and 29 +/- 2.4% in nonatopic
      subjects (P < 0.01). In atopic subjects, a negative correlation was found between
      anti-IgE- or FMLP-induced histamine release and net enhancement by IL-3 (r = 
      0.45, P < 0.02; r = -0.48, P < 0.01, respectively). The results of this study
      indicate that in atopic subjects IgE-mediated histamine release can scarcely be
      enhanced by a basophil response modifier such as IL-3. It is conceivable that the
      frequent basophil stimulation in atopic patients leads to a reduced sensitivity
      to the enhancing effect of IL-3.

PMID- 8874656
TI  - Atopic eczema and other manifestations of atopy: results of a study in East and
      West Germany.
AB  - Within an environmental health study, dermatologic examination of 1273 pre-school
      age children (5-7 years old) was carried out in selected areas of East (n = 287)
      and West (n = 987) Germany in spring 1991. On the basis of comparable genetic
      background, the influence of a different exposure to air pollutants on the
      manifestation of atopic diseases was investigated. Halle an der Saale (East
      Germany) and Duisburg (North/South) as well as Essen (West Germany) were chosen
      as polluted study areas, whereas the countryside town of Borken (West Germany)
      served as a control region. Outdoor pollution with particles and SO2 was
      significantly higher in Halle an der Saale. Of the total study group, 12.9%
      suffered from atopic eczema at the time of examination. The prevalence was
      highest in East Germany (17.5%; adjusted odds ratio [OR] 1.39, confidence
      intervals [GI] 0.77-2.52, compared to Borken). The reported frequencies of hay
      fever and asthma in the total study population were 2% and 1.3%, respectively,
      without significant differences between study sites. Some 34.7% of the children
      showed at least one positive skin prick test reaction; significantly (P < 0.001)
      higher sensitization rates were obtained in western regions (Essen, Duisburg
      South) than in the control region (Borken) and East Germany. Multivariate
      analysis of the prevalence of atopic eczema showed associations with parental
      predisposition (OR 1.52, CI 1.03-2.25), sex (for boys, OR 0.63, CI 0.43-0.92),
      location (Duisburg-South vs Borken OR 0.52, CI 0.30-0.96), month of investigation
      (May vs April, and March vs February OR 0.55, CI 0.37-0.81), contact with rabbits
      (for girls, OR 2.90, CI 1.36-6.19), animal fur in bedrooms (2.17, 1.01-4.67),
      indoor use of gas without hood (1.68, 1.11-2.56), and distance of homes from a
      busy road (< 50 m 1.71, 1.07-2.73). Nonsignificant associations were observed for
      history of helminthic infections (OR 1.61, CI 0.98-2.64) and high parental
      education level (OR 1.83, CI 0.83-4.02). In East and West Germany, atopic eczema
      seems to follow a course different from that of respiratory allergic diseases and
      specific sensitization, a fact which underlines the need for a differentiated
      analysis.

PMID- 8874657
TI  - Honeybee venom allergy: immunoblot studies in allergic patients after
      immunotherapy and before sting challenge.
AB  - By immunoblot techniques, detailed antibody studies were performed with sera of
      20 honeybee-venom-allergic patients during or at the end of specific
      immunotherapy (median duration: 3 years) and before honeybee sting challenge.
      Before immunotherapy, all patients had experienced systemic allergic reactions to
      a honeybee sting, with a mean severity of 3.5 +/- 0.5 according to the Muller
      classification. After the sting challenge, 10 patients (reactors) reacted again
      with a systemic allergic reaction, whereas 10 patients (nonreactors) did not. No
      differences were observed between reactors and nonreactors in total serum IgE and
      specific IgE to honeybee venom at the time of challenge. For immunoblot, honeybee
      venom (RELESS) was separated on 7.5-20% SDS-PAGE. For detection of specific IgE,
      IgG, IgG1, IgG4, and IgM, an alkaline phosphatase-linked second antibody was
      used. Both groups showed 11 antibody-binding bands: at 52, 46, 40, 31, 18.7,
      16.9, 13, 11, 10, 9, and 8 kDa; however, the antibody-binding pattern was
      individual. The reactors differed from nonreactors in showing intense IgE and
      less IgG4 binding to at least one single component of the venom extract. For
      nonreactors, the inverse relationship was observed. The hypothesis, "intensity of
      IgE > or = IgG4 leads to allergic symptoms", was highly significant (P = 0.00026;
      chi-square). These immunoblot findings could offer predictive value in
      distinguishing reactors from nonreactors.

PMID- 8874658
TI  - Serum eosinophil cationic protein (ECP) as a marker of disease activity and
      treatment efficacy in seasonal asthma.
AB  - This study was carried out to determine whether serum eosinophil cationic protein
      (ECP) represents a sensitive marker for disease activity in atopic asthmatic
      patients during the pollen season. The study, in double-blind fashion, was
      performed between February and June 1994. Two groups of 10 seasonal asthmatic
      patients randomly received two different treatments. The first group was treated
      with inhaled beclomethasone dipropionate (BDP) 500 micrograms bid; the second
      received a matched placebo (P). At the beginning and every month, blood samples
      for determination of ECP and eosinophil count were collected and lung function
      (FEV1) and methacholine responsiveness (PD20) were performed. Subjects recorded
      daily symptoms of asthma, salbutamol consumption, and peak expiratory flow (PEF)
      values. In the P group, all indices, except FEV1, showed significant changes
      during the pollen season (P < 0.001). In the BDP group, significant changes were
      detected for symptom score (P < 0.01), salbutamol consumption (P < 0.01), and
      eosinophil number (P < 0.05). Between the two groups, significant differences for
      symptom score (P < 0.001), salbutamol consumption (P < 0.001), ECP levels (P <
      0.05), eosinophil count (P < 0.02), PD20 methacholine (P < 0.02), and PEF values
      (P < 0.01) were detected. Changes in serum ECP significantly correlated with
      changes in other parameters (P < 0.001), except FEV1. Our results provide
      evidence that serum ECP is a sensitive marker for monitoring of the disease
      activity in seasonal asthma. Furthermore, it may offer a useful tool for
      estimating treatment efficacy.

PMID- 8874659
TI  - Inflammatory responses in skin and airways after allergen challenge in brown
      Norway rats sensitized to trimellitic anhydride.
AB  - Trimellitic anhydride (TMA) is a low-molecular-weight compound which causes
      occupational allergy. Brown Norway rats were sensitized to TMA injected
      intradermally (0.3% TMA suspended in oil). Three weeks later, we examined
      responses to either free TMA injected intradermally, or TMA conjugated to rat
      serum albumin (TMA-RSA) given by inhalation (0.5%, nebulized for 15 min). Twenty
      one days after the sensitization, Evans blue dye was given i.v. (20 mg/kg), and
      extravasation of dye in skin was measured 30 min after oil or TMA injections
      (0.03-10% in oil). In a separate series of experiments, we evaluated the
      accumulation of eosinophils in the skin after single and repeated injections of
      TMA (0.03-0.3%). The injection sites were removed and fixed in formalin 18-24 h
      after the last injection. In a third series of experiments, we evaluated the
      effects of airway exposure to TMA-RSA (0.5% in 0.9% saline) on the accumulation
      of eosinophils in the bronchial wall counted with quantitative light microscopy.
      Intradermal injections of free TMA caused a dose-dependent increase of Evans blue
      dye extravasation which was significantly higher in sensitized animals than in
      controls. Skin histology revealed a significant and dose-dependent increase in
      eosinophils after repeated TMA injections in sensitized animals. Exposure to
      aerosolized TMA-RSA caused a significant increase of eosinophils in the bronchial
      wall of sensitized rats compared with nonsensitized rats. Sensitized animals
      showed significantly higher levels of specific IgG and IgE. We conclude that
      brown Norway rats can be used as a model of TMA-induced allergic inflammation,
      mimicking occupational asthma.

PMID- 8874660
TI  - Effects of interleukin (IL)-3 and IL-5 on human eosinophil degranulation induced
      by complement components C3a and C5a.
AB  - It is suggested that eosinophils (Eos) play an important role in the pathogenesis
      of bronchial asthma by releasing cytotoxic cationic eosinophil granule proteins
      and damaging bronchial epithelial cells. However, the exact nature of the actual
      inducer of eosinophil degranulation in vivo is unclear. We examined eosinophil
      cationic protein (ECP) release from human Eos in response to soluble agonists
      such as C5a, C3a, platelet-activating factor, and FMLP with or without
      interleukin (IL)-3 or IL-5 priming. Eosinophil degranulation induced by these
      soluble agonists required the pretreatment of Eos by cytochalasin B even in IL-3
      priming. Among four agonists, C5a was the most effective stimulus of ECP release
      either with or without IL-5 priming. IL-3 and IL-5 remarkably enhanced ECP
      release in Eos triggered by C3a and C5a. The enhancement of ECP release by IL-3
      and IL-5 occurred at 0.1-0.3 ng/ml and became maximal at 10-30 ng/ml,
      concentration-dependently. The enhancement of ECP release by cytokines became
      optimal at an interval of 10 min. Our data support the importance of complement
      components and cytokines in eosinophil degranulation in vivo.

PMID- 8874661
TI  - Once-daily mometasone furoate aqueous nasal spray (Nasonex) in seasonal allergic
      rhinitis: an active- and placebo-controlled study.
AB  - Mometasone furoate aqueous nasal spray (Nasonex) was compared with beclomethasone
      dipropionate (BDP) aqueous nasal spray in a double-blind, randomized, placebo
      controlled, double-dummy, parallel-group study of adults with moderate to severe
      seasonal allergic rhinitis. Patients allergic to at least one tree and/or grass
      aeroallergen received one of the following regimens for up to 4 weeks; mometasone
      furoate 100 micrograms once daily [OD] (n = 126) or 200 micrograms OD (n = 126),
      BDP 200 micrograms twice daily (n = 126), or only placebo spray (n = 123).
      Physician-rated nasal and total symptom scores, and global evaluation of overall
      condition and therapeutic response by physicians and patients, showed that the
      three active treatments were equally effective, and all three were significantly
      superior to placebo at most time points. Overall, mometasone furoate 200
      micrograms OD demonstrated somewhat greater numerical, but not statistical,
      superiority to mometasone furoate 100 micrograms OD at the earliest evaluation
      time point. At the end of treatment, complete or marked relief was obtained in
      77% of patients with mometasone furoate 100 micrograms/day, 79% with mometasone
      furoate 200 micrograms/day, and 74% with BDP, compared with 54% of placebo
      vehicle control patients. Mometasone furoate and BDP were equally well tolerated.
      It was concluded that mometasone furoate adequately controls symptoms of moderate
      to severe seasonal allergic rhinitis, offers the advantage of OD treatment, and
      is well tolerated.

PMID- 8874662
TI  - Tear tryptase levels and allergic conjunctivitis.
AB  - We measured tryptase, a neutral protease stored in the secretory granules of mast
      cells, by solid-phase radioimmunoassay in tears of 12 subjects with vernal
      keratoconjunctivitis (VKC) during remission phases, nine subjects with seasonal
      or perennial allergic conjunctivitis, and eight healthy controls. Mean values of
      tear tryptase levels were significantly (P < 0.02) increased in VKC patients
      (14.5 +/- 13 micrograms/l) when compared to those measured in patients with
      seasonal or perennial allergic conjunctivitis (0.6 +/- 0.1 microgram/l) and in
      controls (3.3 +/- 3.2 micrograms/l). In subjects with allergic conjunctivitis,
      the levels of tryptase, almost undetectable before allergen conjunctival
      challenge, showed a significant increase in the challenged eye 20 min-but not 6 h
      after provocation in 5/9 cases. Our results indicate that VKC a severe ocular
      disease characterized by an increased number and abnormal distribution of mast
      cells in the conjunctiva, also shows elevated levels of tryptase in tears even
      during remission phases. Evidence of mast-cell activation, as revealed by a
      significant increase of tryptase levels in tears, in documented during the early
      phase reaction, but not during the late-phase reaction, of allergic
      conjunctivitis patients challenged topically by specific allergen.

PMID- 8874663
TI  - Allergy to cockroaches in patients with asthma and rhinitis in an urban area
      (Madrid).
AB  - Previous studies have established that cockroach allergens are important
      sensitizing agents in the induction of rhinitis and asthma principally in urban
      areas. This study was undertaken to assess skin test reactivity and specific IgE
      antibody reactivity to extracts of Periplaneta americana (P.a.), Blattella
      germanica (B.g.), B. orientalis (B.o.), and a fecal extract of B. germanica
      (FEB.g.) in a group of patients with rhinitis and asthma living in an urban area
      in Europe. We examined clinical characteristics and aerollergen sensitivities of
      171 consecutive Madrid urban patients with rhinitis and asthma who met the
      criteria for the study. A comprehensive clinical evaluation was followed by skin
      prick test with common allergens and saline extracts of P.a., B.g., B.o., and
      FEB.g. and measurement of serum specific IgE antibody to cockroach extracts. The
      age of patients ranged from 7 to 68 years (mean 20.4 +/- 16). A total of 153
      (90.5%) subjects were atopic and 19 (10%) were considered nonallergic. Pollen
      sensitivity (66.5%) was most prevalent, distantly followed by sensitivity to
      cockroach (25.7%), mite (20%), cat (15.5%), Alternaria alternata (14.5%), dog
      (14%), and food (2%). Skin test reactivity to cockroach extracts was 37 (21.6%)
      to B.o., 20 (11.6%) to P.a., 19 (11.1%) to B.g. and five (2.9%) to FEB.g. Twenty
      one of these patients had rhinitis, 19 rhinitis and asthma, and one only asthma;
      26 had perennial symptoms, while 16 had seasonal (spring) symptoms; three (1.7%)
      patients had only positive prick test to cockroach; all had perennial rhinitis
      and/or asthma. Eighteen (10.5%) patients had specific serum IgE (RAST 1 or 2) to
      B.o., 13 (7.6%) to P.a., and six (3.5%) to B.g. Eighty (46.7%) patients had
      visual evidence of cockroach infestation in their home, mostly B.o.; 31 had
      positive prick test to cockroach (P < 0.0003). The results indicate that
      sensitivity to outdoor allergens (pollen) is more prevalent than to indoor
      allergens. Cockroach sensitization is the most important indoor allergen in our
      area, and B.o. accounts for most cockroach sensitization.

PMID- 8874664
TI  - Occupational egg allergy in confectionary workers.

PMID- 8874665
TI  - Peripheral blood CD8- T-cell subsets in common variable immunodeficiency.

PMID- 8874666
TI  - Anaphylactoid reaction in relation to sialolithiasis.

PMID- 8874667
TI  - In vitro activity of Cinnamomum zeylanicum against azole resistant and sensitive
      Candida species and a pilot study of cinnamon for oral candidiasis.
AB  - Fluconazole-resistant Candida species are an emerging problem. In this report,
      the in vitro activity of C. zeylanicum against fluconazole-resistant and
      susceptible Candida isolates is described. The MICs of the bark of C. zeylanicum
      ranged from < 0.05-30 mg/ml, and were slightly better than commercially available
      cinnamon powder. Trans-cinnamaldehyde and O-methoxycinnamaldehyde had MICs of
      0.03-0.5 mg/ml. The MICs of selected cinnamon candies and gums generally ranged
      from 25-100 mg/ml. Five patients with HIV infection and oral candidiasis received
      a commercially available cinnamon preparation for one week. There of the five
      patients had improvement of their oral candidiasis. Clinical trials will be
      necessary to determine the usefulness of cinnamon for the treatment of mucosal
      candidiasis.

PMID- 8874668
TI  - Cordyceps sinensis as an immunomodulatory agent.
AB  - Effects of various fractions of methanol extracts from fruiting bodies of
      Cordyceps sinensis on the lymphoproliferative response, natural killer (NK) cell
      activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor
      necrosis factor-alpha (TNF-alpha) production on human mononuclear cells (HMNC)
      were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51)
      significantly inhibited the blastogenesis response (IC50 = 71.0 +/- 3.0 and 21.7
      +/- 2.0 micrograms/ml, respectively), NK cell activity (IC50 = 25.0 +/- 2.5 and
      12.9 +/- 5.8 micrograms/ml, respectively) and IL-2 production of HMNC stimulated
      by PHA (IC50 = 9.6 +/- 2.3 and 5.5 +/- 1.6 micrograms/ml, respectively). TNF
      alpha production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (IC50
      = 2.7 +/- 1.0 and 12.5 +/- 3.8 micrograms/ml, respectively). These results
      indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that
      immunosuppressive ingredients are contained in Cordyceps sinensis.

PMID- 8874669
TI  - Anti-inflammatory and radical scavenge effects of Arctium lappa.
AB  - The effects of Arctium lappa L. (root) on anti-inflammatory and free radical
      scavenger activity were investigated. Subcutaneous administration of A. lappa
      crude extract significantly decreased carrageenan-induced rat paw edema. When
      simultaneously treated with CCl4, it produced pronounced activities against CCl4
      induced acute liver damage. The free radical scavenging activity of its crude
      extract was also examined by means of an electron spin resonance (ESR)
      spectrometer. The IC50 of A. lappa extract on superoxide and hydroxyl radical
      scavenger activity was 2.06 mg/ml and 11.8 mg/ml, respectively. These findings
      suggest that Arctium lappa possess free radical scavenging activity. The
      inhibitory effects on carrageenan-induced paw edema and CCl4-induced
      hepatotoxicity could be due to the scavenging effect of A. lappa.

PMID- 8874670
TI  - Anti-inflammatory effects of emodin from ventilago leiocarpa.
AB  - Emodin, a major component of the AcOEt and CHCl3 fractions from Ventilago
      leiocarpa Bunge (Rhamnaceae), was isolated. It exhibited apti-inflammatory effect
      on carrageenan-induced edema in rats.

PMID- 8874672
TI  - The protective effect of Alstonia scholaris R. Br. on hepatotoxin-induced acute
      liver damage.
AB  - The hepatoprotective effect of Alstonia scholaris R. Br. on liver injuries
      induced by carbon tetrachloride (CCl4). beta-D-galactosamine, acetaminophen and
      ethanol were investigated by means of serum-biochemical and histopathological
      examinations. Post treatment of A scholaris reduced dose-dependently the
      elevation of serum transaminases level and histopathological changes such as cell
      necrosis, inflammatory cell infiltration, which were caused by the single
      administration of 32 microliters/kg CCl4 or 600 mg/kg acetaminophen in mice. A.
      scholaris significantly lowered 288 mg/kg beta-D-galactosamine induced serum
      transaminases elevation in the serum-biochemical analysis in rats. A tendency was
      also shown to inhibit cell necrosis and inflammatory cell infiltration caused by
      beta-D-galactosamine in histopathological examination. All serological and
      histopathological effects of A. scholaris were compared with those of Bupleurum
      chinense, which has been reported previously as a treatment criteria of
      hepatitis.

PMID- 8874671
TI  - Induction of cytochrome P-450-linked monooxygenase system in rat liver microsomes
      by xiao-chaihu-tang.
AB  - The administration of Xiao-Chaihu-Tang (TJ-9) for 2 weeks induced a 25% increase
      in the content of cytochrome P-450 in female rat liver microsomes, while the
      content in male rats remained unchanged. The enzymatic activities toward various
      xenobiotics were stimulated in female rats, the levels being in the range of 125
      250% of those in the control rats. Among these xenobiotics, the metabolic rates
      for substrates of cytochrome P-450 2E1 were significantly enhanced in female
      rats. On the other hand, the activities toward various xenobiotics in male rats
      were unchanged. When 3-methylcholanthrene was given to rats for a week, the
      augmentation of cytochrome P-450 content and the stimulation of xenobiotic
      metabolism were observed. However, co-administration of TJ-9 did not alter the
      effect of 3-methylcholanthrene described above.

PMID- 8874673
TI  - Pharmacotherapeutic effects of toki-shakuyaku-san on leukorrhagia in young women.
AB  - Toki-shakuyaku-san is a traditional Chinese herbal prescriptions that is composed
      of 6 herbal plants, i.e., peony root, atractylodes lancea rhizome, alisma
      rhizome, hoelen, cnidium rhizome and Japanese angelica root. Administration with
      Toki-shakuyaku-san normalized irregular menstrual cycle, healed cervical pseudo
      erosion and reduced leukorrhagia in young women who had insufficient luteal
      function.

PMID- 8874675
TI  - Influence of acupuncture and pharmacotherapy on sensitivity of sensory systems to
      alcohol irritants in patients with alcoholism.
AB  - The sensitivity of an alcoholic's sensory systems (SS) to alcohol therapy is a
      good indication of treatment efficacy in this disease. In this study, we compare
      pharmacotherapy (PHT) and acupuncture therapy (AP) on the sensitivity of visual
      (VL), acoustic (AC), olfactory (OL) and taste (TS) systems to alcohol irritants
      (AI). The results showed that PHT changed the threshold sensitivity of SS to AI
      but did not cause aversion of SS to AI. In acupuncture treatment, results can be
      divided into four groups: Group 1, no aversion of AC was produced to AI; Group 2,
      no aversion of TS and OL were produced to AI; Group 3, no aversion of VL to AI;
      and group 4, no aversion was recorded to AI. Supposedly, one of the sensory
      systems of the organism is genetically leading in organizing sensory-emotional
      operation of information, and other SS are subordinates. Therefore, before
      acupuncture treatment for alcoholism, it is necessary to cause excitation to the
      ethanol-dependent system (target-system) by means of irritation to the leading
      sensory system of the patient.

PMID- 8874674
TI  - Effects of tetramethylpyrazine phosphate and sodium ferulate alone or in
      combination on hemodynamics in anesthetized dog.
AB  - Hemodynamic actions of intravenous (iv) administration of tetramethylpyrazine
      phosphate (TMPP) and sodium ferulate (SF) alone or in combination were studied in
      anesthetized dogs. When given alone, TMPP increased left ventricular systolic
      pressure (LVSP), peak positive first derivative of left ventricular pressure
      (+LVdp/dt), coronary blood flow (CBF) and heart rate (HR) while decreasing mean
      aortic pressure (mAoP). SF alone did not produce any significant hemodynamic
      changes. When the two were administered in combination, SF antagonized dose
      dependently the hemodynamic actions of TMPP. Results of this study did not
      support the efficacy of combined treatment of Ligusticum wallichi and Angelica
      root, which contain TMPP and SF respectively.

PMID- 8874676
TI  - Effect of transcutaneous nerve stimulation on esophageal function in normal
      subjects--evidence for a somatovisceral reflex.
AB  - Transcutaneous stimulation (TNS) at esophageal acupuncture points decreases lower
      esophageal sphincter (LES) pressures in patients with achalasia. We examined the
      effect of TNS on esophageal motility and vasoactive intestinal peptide (VIP)
      levels in normal subjects. TNS was applied to either hand or foot (placebo) in 10
      volunteers. Esophageal and LES pressures were recorded and blood was drawn for
      VIP analysis. Hand TNS improved LES relaxation and percent of peristaltic
      contractions to swallows, and decreased the number of spontaneous contractions.
      Foot TNS decreased only spontaneous contractions while LES pressures and VIP
      levels were unchanged. We conclude that a somatovisceral pathway involving the
      esophagus exists.

PMID- 8874677
TI  - Acute effect of qigong training on stress hormonal levels in man.
AB  - We observed the acute effects of Qigong training on the levels of human
      endogenous opioid peptides, such as beta-endorphin, and other stress hormones
      [adrenocorticotrophic hormone (ACTH), cortisol, and dehydroepiandrosterone
      sulfate (DHEA-S)] in a group of ChunDoSunBup Qigong trainees. At pre (-10 min),
      mid (40 min) and post (70 min) time of training, blood was taken for the
      determination of plasma level of hormones. The level of beta-endorphin was
      significantly increased during the mid-time of training while the level of ACTH
      declined at the mid- and post-time of training. Cortisol and DHEA-S were not
      significantly changed during training. This result suggests that Qigong training,
      as a stress coping method, affects and plays a role in hormonal regulation
      related to the maintenance of homeostasis in man.

PMID- 8874678
TI  - Pulse spectrum analysis of chemical factory workers with abnormal blood test.
AB  - Double blind tests to check the correlation between pulse diagnosis and liver
      function tests were performed. Blood tests including T-Bil, D-Bil, SGOT and SGPT
      of 70 chemical factory workers were compared with pulse analysis. Special
      attention was paid to the indicators of liver and lung meridians for pulse
      diagnosis. It was found that using the criterion (1) C1 > or = 3+ and C1 + C4 >
      or = 4+ (hyperfunction) and (2) C1 < or = 3-(hypofunction) as abnormal liver
      meridian (for C1, every 5% above normal give one +, every 5% below normal give
      one-; for C4 every 10% above normal give one +, every 10% below normal give one 
      ). The correlation or agreement between the blood tests and the pulse diagnosis
      was very high (noncorrelation chance checked by X2-test, P < 0.001, degree of
      agreement checked by Kappa test Ka = 0.61 which means a substantial
      relationship). Suggestions such as more tests, more criteria and precautions for
      future study are also proposed.

PMID- 8874679
TI  - Put prevention into practice.

PMID- 8874680
TI  - Training preventive medicine residents to put prevention into practice.

PMID- 8874681
TI  - Overweight and obesity in Native-American adolescents: comparing nonreservation
      youths with African-American and Caucasian peers.

PMID- 8874683
TI  - Point: nutrition counseling and the physician--why reinvent the wheel?

PMID- 8874684
TI  - Acceptance and use of Put Prevention into practice materials at an inner-city
      hospital.
AB  - Many studies indicate that physicians' prevention practices frequently differ
      from published guidelines. Put Prevention into Practice (PPIP) consists of a
      variety of paper-based materials for providers, patients, and the office setting
      designed to enhance the delivery of clinical preventive services. Prototype PPIP
      materials were distributed to physicians and patients at the Harlem Hospital
      medical clinic in conjunction with a series of prevention lectures for
      physicians. Acceptance and use of these materials were assessed through self
      administered questionnaires for physicians and structured interviews for
      patients. A regression analysis was conducted to assess correlates of physician
      use of PPIP materials. Physicians reported a high degree of use of and
      satisfaction with PPIP materials. Multiple regression analysis indicated that the
      physicians' perceived self-efficacy in their ability to provide preventive
      counseling to patients at baseline was significantly associated with increased
      use of PPIP materials. When controlling for baseline physician self-efficacy,
      physicians whose self-efficacy increased during the study period were more likely
      to have used the materials. A majority of patients (53%) reported that the main
      patient-based component of the program-a pocket-sized booklet providing health
      education information and record-keeping of preventive tests and procedures-was
      very useful. Results from this study indicate a high degree of acceptance of
      prototype PPIP materials by physicians and patients at an inner-city hospital.
      Educational programs for physicians that enhance physician self-efficacy may be
      more effective in helping practitioners to adopt office-based prevention
      resources. Medical Subject Headings (MeSH): prevention, primary care, preventive
      health services, clinical practice patterns.

PMID- 8874685
TI  - Health promotion practices among physicians.
AB  - Personal belief concerning both the validity of health promotion and the
      physician's ability to influence patient behavior may affect how much effort a
      physician spends on health promotion strategies. We assessed these beliefs
      through a mail survey to physicians practicing in a predominantly rural southern
      state in 1987 (n = 83) and 1991 (n = 96). Response rates in both studies exceeded
      75%. The instrument was obtained from similar studies conducted in Massachusetts
      in 1981 and Maryland in 1983. Between 1987 and 1991 we found slight improvements
      in the perceived importance of many health behaviors, but significant improvement
      was observed in the importance of reducing intake of dietary saturated fat (66%
      in 1987 to 80% in 1991; P < .05). Less than 10% of the physicians thought they
      could be "very successful" in modifying patients' behaviors. However, in 1991
      physicians perceived that their ability to be "very successful" in helping
      patients to modify their behavior would increase threefold (8%-24% for exercise;
      4%-18% for smoking) if given appropriate support. Although the type of
      appropriate support was not identified, the credibility of physician's advice in
      promoting health changes is important. These results suggest that efforts should
      be made to provide support to physicians who are inclined to discuss health
      behavior changes with their patients. Medical Subject Headings (MeSH): dietary
      fats, exercise, patient education, physician's practice patterns, smoking.

PMID- 8874686
TI  - Remember Tuskegee: public health student knowledge of the ethical significance of
      the Tuskegee Syphilis Study.
AB  - The ethical problems that surrounded the Tuskegee Syphilis Study prompted
      widespread public criticism when they first surfaced in 1972; the Tuskegee Study
      remains an important case in bioethics. We recently examined public health
      student knowledge of the ethical significance of the Tuskegee Study as part of an
      ethics curriculum needs assessment at Tulane University. A brief questionnaire
      was administered to 236 graduate students currently enrolled in seven
      epidemiology courses. Basic demographic information was obtained along with
      information about degree program. A series of questions was then asked to assess
      student knowledge of bioethics including the ethical significance of the Tuskegee
      Study. Only 19% (46 of 236) of the students demonstrated knowledge of the ethical
      significance of the Tuskegee Study. Knowledge of the Tuskegee Study's ethical
      significance was higher among students who were from the United States and those
      who were enrolled in the epidemiology program (P < .05). The ethical problems
      that surrounded the Tuskegee Study have rarely been encountered in public health.
      However, this important case stands as an exemplar of the potential for ethical
      abuses in human subjects research. Such cases ought to be highlighted in public
      health curricula. Medical Subject Headings (MeSH): blacks, African Americans,
      educational curriculum, epidemiology, ethics, public health, racism.

PMID- 8874687
TI  - Model curricula in public health ethics.

PMID- 8874688
TI  - Effect of training and a structured office practice on physician-delivered
      nutrition counseling: the Worcester-Area Trial for Counseling in Hyperlipidemia
      (WATCH).
AB  - We examined the effectiveness of a training program for physician-delivered
      nutrition counseling, alone and in combination with a structured office practice
      environment for nutrition management, on physicians' counseling practices. Forty
      five primary care internists and 1,278 of their patients in the top quarter of
      the cholesterol distribution at a central Massachusetts health maintenance
      organization (the Fallon Clinic) were enrolled into a randomized controlled
      trial. Physicians were randomized by site into three conditions: (1) usual care,
      (2) physician nutrition counseling training, and (3) physician nutrition
      counseling training plus a structured office practice environment for nutrition
      management (prompts and the provision of lipid results and counseling
      algorithms). A randomly selected 325 patients were given a 10-item patient exit
      interview (PEI) assessing whether the physician provided advice; assessed past
      changes, barriers, and resources; negotiated specific plans and goals; provided
      patient materials; referred the patient to a dietitian; and developed plans for
      follow-up. Condition 3 physicians demonstrated significantly greater
      implementation of the nutrition counseling sequence than did physicians in either
      of the other two conditions (P < .0001). Referrals to nutrition services were
      markedly reduced in condition 2, despite PEI scores no different than those in
      condition 1. Higher PEI scores for patients seen by physicians in condition 3
      were stable for as long as two years beyond training. Primary care internists,
      when provided with both training in counseling techniques and a supportive office
      environment, will carry out patient counseling appropriately. Training alone,
      however, is not sufficient and may be counterproductive. Medical Subject Headings
      (MeSH): hypercholesterolemia, diet therapy, coronary disease, health behavior,
      primary health care, medical education, managed care programs.

PMID- 8874690
TI  - Counseling strategies for obese patients.
AB  - Counseling strategies usually assume that an individual is ready to change;
      however this assumption is probably not true for many obese individuals seeking
      medical care. Since individuals progress through a series of stages of change,
      some may not yet be ready to change. The transtheoretical model of behavior
      change proposes that individuals move through stages of change: precontemplation,
      contemplation, preparation, action, and maintenance. This model has been
      successfully applied to a range of addictive behaviors. The application of the
      transtheoretical model of behavior change to obesity treatment holds promise
      because interventions that match treatment strategies to an individual's stage of
      change may be more effective than current treatments. This article reviews the
      potential benefits of using the transtheoretical model for weight management in
      the primary care setting. Medical Subject Headings (MeSH): obesity, counseling,
      behavior.

PMID- 8874689
TI  - Teaching dietary counseling skills to residents: patient and physician outcomes.
      The CADRE Study Group.
AB  - Our objective was to determine whether an educational intervention and prompting
      intervention for physicians improved dietary counseling of patients with high
      blood cholesterol and resulted in beneficial changes in patients' diets and
      cholesterol levels. We instituted a factorial design, multicenter, randomized,
      placebo-controlled trial to test two interventions. We tested the trial at
      continuity care clinics of internal medicine residents at seven community and
      university medical centers in the northern and eastern United States. Our
      participants were 130 internal medicine residents and 254 adult outpatients with
      blood cholesterol levels of 240-300 mg/dL. Interventions included an educational
      program for resident physicians designed to improve their skills and confidence
      in dietary counseling (two one-hour sessions with specially prepared printed
      materials for use in counseling) and a prompting intervention, which was a
      fingerstick blood cholesterol determination prior to the patient's clinic visit.
      Resident physicians' knowledge, attitudes, and self-reported behaviors were
      assessed prior to the intervention and 10 months later using chart audits and
      questionnaires. Residents' behaviors were also assessed by exit interviews with
      patients. Patients' knowledge, attitudes, behaviors, and fingerstick blood
      cholesterol levels were measured at baseline and 10 months later. The educational
      program increased the percentage of physicians who were confident in providing
      effective dietary counseling (baseline of 26% to 67%-78%; P < .01). The prompting
      intervention approximately doubled the frequency of physician counseling (P =
      .0005) and increased the likelihood that patients would try to change their
      diets. When both interventions were combined, most outcomes were better, although
      not statistically significant. Cholesterol levels, however, decreased only
      marginally and were no different among groups at 10-month follow-up. Despite
      success in changing physicians' attitudes and behaviors and increasing patients'
      willingness to change their diets, there was no significant change in patients'
      cholesterol levels. Medical Subject Headings (MeSH): randomized controlled trial;
      cholesterol; patient education; behavior therapy; education, medical; diet.

PMID- 8874691
TI  - Perceptions and opinions on the performance of Pap smears: a survey of clinicians
      using a commercial laboratory.
AB  - Office-based clinicians play a major role in cervical cancer screening in the
      United States, but little is known about their specific knowledge and
      understanding of the technical aspects of obtaining an adequate Pap smear. We
      surveyed 186 office-based clinicians using a major commercial laboratory for
      cytology services to obtain their opinions regarding the technical adequacy of
      Pap smears, collection procedures, and methods of communicating test results to
      patients. There was an 80.1% response rate. Two thirds of the respondents were
      men. Cytobrush use was reported significantly more by female clinicians.
      Respondents varied in reported rotation of the cytobrush, from 90 degrees to
      greater than 360 degrees. More female than male clinicians appropriately
      indicated that inflammation and heavy vaginal discharge caused sampling
      difficulties. Approximately half of the respondents believed that errors in
      cervical screening most often resulted from sampling the cervix or preparation of
      the Pap smear. Nineteen percent reported that ectocervical cells were not
      necessary for an adequate smear to be reported. Just over 25% of respondents
      indicated they did not report normal Pap smear results to the patient. The
      results indicate differences between clinicians by gender and specialty in
      reported knowledge, understanding, and technique in cervical cancer screening.
      The differences suggest that targeted education in this population may be
      important to improve the quality of cervical cancer screening. Medical Subject
      Headings (MeSH): screening; neoplasms, cervical; Papanicolaou smear; diagnosis,
      laboratory.

PMID- 8874692
TI  - Attitudes and practices of primary care physicians for prostate cancer screening.
AB  - Prostate cancer screening with digital rectal examination (DRE) and prostate
      specific antigen (PSA) is recommended by several professional organizations. Our
      objective was to assess the prostate cancer screening practices and attitudes
      reported by primary care physicians. We randomly surveyed 454 Arizona primary
      care physicians, subsequently excluding 124 ineligible subjects. Overall, 141 of
      329 eligible physicians completed the survey (42.9%). Survey data included
      physician demographics, practice characteristics, screening and follow-up
      strategies, and attitudes toward screening. One hundred thirty-one physicians
      (93%) reported screening asymptomatic men with DRE or PSA. Respondents generally
      agreed that screening tests were accurate and that early detection was
      beneficial. Screening began at an average patient age of 45 years, though 7.8% of
      respondents began screening men younger than 40 years and 7.0% began screening
      men older than 50 years. PSA levels ranging from 3.9 to 40 ng/mL were considered
      abnormal, and 11.6% of respondents used a cutpoint higher than 10 ng/mL. Primary
      care physicians report a high rate of screening for prostate cancer and consider
      PSA and DRE accurate and useful tests. Screening practices, however, varied
      considerably between physicians. The screening of younger men reported by
      practitioners would tend to increase the rate of false-positive tests, while
      using a high cutpoint for PSA and delaying screening beyond age 50 years would
      decrease the chance for early detection. These screening practices may increase
      health care costs without necessarily leading to improved health outcomes.
      Medical Subject Headings (MeSH): prostatic neoplasms, prostate-specific antigen,
      primary health care, screening.

PMID- 8874693
TI  - Inadequate follow-up of abnormal mammograms.
AB  - Routine mammographic screening increases detection of nonpalpable breast cancer.
      Timely follow-up of abnormalities is essential because delays may lead to
      postponement of treatment and decreased survival for women who have cancer. The
      purpose of this study was to determine the percentage of women with an abnormal
      mammogram who do not have adequate follow-up and to determine factors associated
      with inadequate follow-up. The study was conducted in a metropolitan health
      system that includes a large urban teaching hospital in Detroit and 26 ambulatory
      care centers. From the radiology database, all women with an abnormal screening
      mammogram performed between January 1, 1992, and July 31, 1992 were identified.
      We defined adequate follow-up as follow-up within three months of due date.
      Follow-up status was determined using medical records and telephone interviews.
      The percentage of women with inadequate follow-up was calculated. Relative risks
      compared percentages of women with inadequate follow-up according to demographic
      and screening-related variables. We calculated adjusted relative risks using
      multivariate binomial regression. We identified 1,249 women with abnormal
      screening mammograms. Inadequate follow-up occurred for 226 (18.1%) of the women.
      Among women with follow-up recommended in 4-6 months, 36.8% had inadequate follow
      up. Among women with immediate follow-up recommended (obtain additional views or
      outside films for comparison, ultrasound, biopsy, or surgical referral), 7.2% had
      inadequate follow-up. Inadequate follow-up was associated with lower estimated
      household income and no history of previous mammogram. Among women with
      inadequate follow-up who were interviewed, 87% reported that they had been
      notified of their results. We found that the percentage of women with inadequate
      follow-up of abnormal mammograms is high, especially among women who require six
      month follow-up. Women with low income and no history of a previous mammogram
      were at greatest risk for inadequate follow-up. These results document a
      previously unrecognized problem with mammography screening and suggest that the
      implementation of tracking systems to ensure timely follow-up of abnormal
      screening mammograms is essential. Medical Subject Headings (MeSH): mammography,
      follow-up, screening.

PMID- 8874694
TI  - Bridge over troubled waters.

PMID- 8874695
TI  - Obstacles to the public health.

PMID- 8874696
TI  - A protocol for community-based research.

PMID- 8874697
TI  - Cooperative agreements between academic professional associations and the Centers
      for Disease Control and Prevention.

PMID- 8874698
TI  - A model immunization demonstration for preschoolers in an inner-city barrio, San
      Diego, California, 1992-1994.
AB  - An immunization demonstration project was conducted in an inner-city Latino
      neighborhood in San Diego to address underimmunization of children of preschool
      age. The project attempted interventions on consumer, provider, and system levels
      to reduce barriers to immunization and raise immunization rates. Free walk-in
      immunization clinics with emphasis on cultural sensitivity and that incorporated
      computerized reminder/recall were established. An educational series was offered
      to community health center (CHC) providers, and extensive community-based
      outreach and education took place in schools, churches, a WIC site, etc.
      Evaluation activities included preintervention and postintervention provider
      knowledge, attitudes, and practice surveys, CHC chart audits, and household
      surveys in the intervention ZIP code area and a control ZIP code area.
      Immunization coverage for 4DPT, 3OPV, and 1MMR (4:3:1) among two-year-olds
      increased significantly from 37% to 50% overall, and to 59% in the 1991 birth
      cohort in the intervention area compared to a one percentage point overall
      increase in the control area. Coverage improved significantly and missed
      opportunities decreased in one intervention CHC that participated most actively
      in educational inservices. While the Year 2000 U.S. Public Health Service
      objective of 90% 4:3:1 coverage for two-year-olds was not achieved over the 21
      month course of the project, the results approached the 1996 single-antigen
      objectives. This demonstration underscores the importance of multilevel
      interventions including low cost, no appointment, and culturally appropriate
      immunization services for the indigent; the use of computerized reminder systems;
      and provider assessment, education, and feedback in the effort to raise preschool
      immunization levels. Medical Subject Headings (MeSH): immunization, preschool-age
      children, health promotion, provider education, immunization monitoring and
      follow-up systems, pediatric immunization standards, household surveys.

PMID- 8874699
TI  - Collaborative needs assessment and systems development in Alabama: Process and
      products.
AB  - This article describes the implementation of a collaborative project and its
      results, involving a department of maternal and child health (DMCH) in a school
      of public health and a state department of public health. The state received a
      federal grant to enhance systems development for women and children. Adequate
      information regarding the existing system of health care was lacking. The state
      contracted with the DMCH for assistance in designing and conducting a needs
      assessment, whose purpose was to (1) identify strengths and weaknesses in the
      state system of care, (2) provide baseline information for targeting resources
      and measuring change, and (3) initiate an on-going process of assessment and
      evaluation of need. The DMCH collected data about financial and nonfinancial
      barriers to care from state-level health agency and organization experts, county
      level service personnel, and consumers. The contributions to understanding the
      needs of the state offered by the information garnered in the three surveys
      helped the state in setting immediate and long-range objectives. The presence of
      the school of public health and the focus of its particular DMCH on assisting
      state agencies provided an atmosphere in which the state could ask for assistance
      and the university could respond in a way that was useful and relevant to the
      state's needs. Medical Subject Headings (MeSH): assessment, health planning,
      health priorities, interprofessional relations, program planning, public health.

PMID- 8874700
TI  - A regional integrated information system to assure maternal-child health
      services: a progress report.
AB  - Priorities for improving the health of our nation include rebuilding the public
      health infrastructure through increasing assessment, policy development, and
      assurance capacities in our communities. Capacity building necessitates
      formalizing and strengthening public health practice linkages to achieve Year
      2000 objectives. Determining progress in achieving objectives requires
      development of public health infrastructure surveillance and data system
      capabilities. The Tracking Center of Tracking and Outreach Program for St. Louis
      (TOPS), through unique collaboration among academic and practice partners, laid
      the foundation for a Regional Integrated Information System (RIIS) by developing
      a centralized maternal-child health data base for prenatal and pediatric care
      providers. The RIIS model provides an example of a capacity building system
      designed to provide public health surveillance, assessment, planning, and
      evaluation capabilities. Medical Subject Headings (MeSH): health information
      systems, prenatal care, immunization, maternal-child health care, public health
      surveillance.

PMID- 8874701
TI  - Challenges faced by the HIV health services planning council in Oakland,
      California, 1991-1994.
AB  - This study reports the findings of a case study of the health services planning
      council established in the Oakland, California, eligible metropolitan area (the
      Oakland EMA) under Title I of the Ryan White Comprehensive AIDS Resources
      Emergency Act of 1990 (the CARE Act). We gathered primary data through
      observation of planning council meetings, examination of documentary evidence,
      and in-depth interviews with key participants. An important finding of this study
      was the inconsistency observed between the rational, linear planning model
      embedded in the CARE Act legislation and the politicized, emergent, and, at
      times, chaotic planning process actually observed in the Oakland EMA. The primary
      reasons for this inconsistency included confusion among council members about the
      planning council's responsibilities and authority, as well as its relationship
      with the local health department; limitations on administrative support at the
      local level; reluctance of program administrators at the federal level to provide
      advice concerning development of the council; allegations of conflict of interest
      among members of the council; pre-existing societal tensions and divisions;
      concerns about the representativeness of the council's membership; competition
      among providers of services for funding; conflicting demands for services by
      persons affected by HIV disease; disagreements between the council and providers
      of services over policies and procedures for administering the services
      contracts; and concerns about the council's involvement in the selection of
      specific agencies for funding, its lapses in compliance with rules of order, and
      its failure to accurately record minutes of all of its meetings. Despite the
      challenges faced by the Oakland planning council, it was able to meet its Title I
      obligations, which resulted in significant increases in the availability of
      medical and social services for persons affected by HIV disease. However, dealing
      with the confusion and conflicts described above consumed a considerable amount
      of the planning council's time and energy and eventually required a complete
      reorganization of the council to assure its stability and the legitimacy of the
      Title I program at the local level. Medical Subject Headings (MeSH): health
      planning councils; health planning organizations; health care coalitions;
      organization and administration; organizational innovation; models,
      organizational.

PMID- 8874702
TI  - Modifying the environment: a community-based injury-reduction program for elderly
      residents.
AB  - The Department of Public Health, City and County of San Francisco, established
      the Community and Home Injury Prevention Program for Seniors (CHIPPS) to reduce
      the rate of unintentional injuries among elderly residents. Through a
      collaboration between the CHIPPS program, the University of California at
      Berkeley School of Public Health and the University of California at San
      Francisco School of Medicine, we tested the hypothesis that providing minor home
      safety modifications would reduce rates of falls, scalds, and burns. A one-group,
      pretest-posttest design was used to compare self-reported falls, scalds, and
      burns for six-month periods before and after the intervention. The intervention
      used 10 person-hours of unskilled labor and $93 worth of materials on average and
      included home safety assessments and modifications such as removing clutter;
      installing hand rails, grab bars, nonskid strips; and securing rugs and
      electrical cords. Reported falls were reduced by 60% after the intervention, from
      0.81 to 0.33 falls per person year (p < .01). Scalds were reduced from 9 to 0 (P
      < .01) and burns from 7 to 0 (P < .02) during the six-month periods before and
      after the intervention. Some of the apparent effect may be due to differential
      reporting. This community-based program to reduce hazards in the home
      environments of senior citizens was feasible, well accepted, and probably
      effective in preventing falls, burns, and scalds. Medical Subject Headings
      (MeSH): accidental falls/prevention and control, aged, safety.

PMID- 8874703
TI  - Stabilizing the HIV/AIDS workforce: lessons from the New York City experience.
AB  - The Ryan White Title I Personnel Needs Study described here is an evaluation of
      the human resource needs of HIV/AIDS service agencies in New York City. The
      research presented here was conducted in collaboration with researchers from the
      Medical and Health Research Association and the New York City Department of
      Health and the Planning and Evaluation Committee of the New York City HIV Health
      and Human Services Planning Council. The assessment is divided into two
      components. The first component is a survey of 100 key informants from HIV/ AIDS
      service agencies. The second component is a detailed staffing survey of 70
      personnel directors of HIV/AIDS service agencies. HIV/AIDS service directors
      perceived staff recruitment as a more difficult process than staff retention,
      regardless of agency type. Vacancy rates at the surveyed agencies varied by
      professional category; they were especially high in the category of nurse
      practitioners (13%) and outreach/education workers (15%). Agencies stressed that
      incentives that would positively affect recruitment and retention should be
      tailored to address the concerns of varied health care and social service
      professionals. In addition, agencies were not routinely able to provide some
      incentives deemed effective such as higher salaries, housing subsidies, and
      smaller caseloads. To reduce recruitment and retention problems, agency
      informants recommended a variety of incentive programs including malpractice
      insurance for physicians, flexible hours for full-time employees (including case
      managers, nurses, physician's assistants), smaller caseloads, and a decrease in
      the proportion of staff time devoted to direct client contact. Overall health
      care trends including truncated federal budgets, state Medicaid cutbacks, and the
      rapid conversion to managed care all affect the quality of patient care and of
      the work setting for health care and social service providers serving persons
      with AIDS. Medical Subject Headings (MeSH): AIDS, health personnel, employment
      supported, employee workload, staff attitude.

PMID- 8874704
TI  - The impact of patient education about the effect of zidovudine on HIV perinatal
      transmission: knowledge gain, attitudes, and behavioral intent among women with
      and at risk of HIV.
AB  - The termination of the perinatal HIV transmission trial, ACTG 076, by the Data
      Safety and Monitoring Board in February 1994 because of the efficacy of
      zidovudine (ZDV) in substantially reducing maternal-infant HIV transmission has
      created a considerable need for efficacious patient education approaches and
      materials for women with and at risk of HIV infection. Complexities surrounding
      patients' decisions to use ZDV in accordance with the treatment arm protocol of
      this study must be communicated to women, especially the consequences for both
      themselves and their potential children. In March 1994, a public-private
      partnership was formed to develop and test the impact of patient education
      information on 076 and to explore cultural differences in decision-making
      surrounding ZDV use during pregnancy. Objectives were (1) to develop an
      efficacious patient informational booklet on the results of ACTG 076 and (2) to
      determine the differential attitudes and behavioral intentions of women toward
      taking AZT during pregnancy. A multi-disciplinary group of providers and
      researchers developed the patient education booklet and field-tested it in five
      New York City area sites. Subjects were a multiethnic group of women of
      childbearing age who were predominantly HIV-positive or at risk of HIV infection
      (n = 120). This 076 education resulted in a substantial increase in intention to
      use ZDV to reduce perinatal transmission despite full disclosure of the unknowns
      (P < .001). There were differences in knowledge acquired between racial/ethnic
      groups, which must be viewed cautiously since the study did not assess
      socioeconomic status adequately. Attitudes toward ZDV (P < .05), trust in health
      care providers (P < .03), and opinions on whether testing should be voluntary (P
      < .02) also varied by race/ethnicity. Medical Subject Headings (MeSH): perinatal
      transmission, AIDS education, pregnancy, HIV, ACTG 076.

PMID- 8874705
TI  - A balancing act: the tension between case-finding and primary prevention
      strategies in New York State's voluntary HIV counseling and testing program in
      women's health care settings.
AB  - This study sought (1) to identify factors that influence women's willingness to
      accept voluntary HIV counseling and testing at New York State Family Planning
      Programs (FPPs) and Prenatal Care Assistance Programs (PCAPs) and (2) to evaluate
      the effectiveness of such a voluntary counseling and testing program. Telephone
      interviews elicited organizational-level data from 136 agencies; a combination of
      telephone and face-to-face interviews was used to gather provider data from 98
      HIV counselors; and client data were gathered from 354 women in face-to-face
      interviews at counseling sites. Slightly fewer than 60% of women agreed to be
      counseled, and, of those, under half consented to an HIV test at the counseling
      site. Approximately two thirds of the women who were tested returned for their
      results and posttest counseling. Clients' recall of pretest counseling content
      was relatively poor. Bivariate and regression analyses suggest that client,
      provider, and organizational factors are all associated with rates of pretest
      counseling and testing. The current voluntary counseling and testing program is
      achieving only moderate success. Although a substantial number of clients accept
      HIV counseling, many women remain reluctant to consent to HIV testing, and many
      who accept testing do not return for their results. Moreover, among those who
      receive pretest counseling, many do not recall important informational content,
      which suggests variation may exist in the quality of counseling or that one-time
      HIV counseling interventions are insufficient to communicate complex information.
      Medical Subject Headings (MeSH): AIDS, HIV serodiagnosis, women's health, patient
      education.

PMID- 8874706
TI  - Gender differences in HIV-related self-reported knowledge, attitudes, and
      behaviors among college students.
AB  - A survey of 265 college students was conducted to determine HIV-related
      knowledge, attitudes, behavior, and perceived self-efficacy with regard to
      engaging in HIV-protective behaviors. A self-administered 52-item survey was
      completed by 265 college students (60% response rate). Resident advisors in
      college dormitories distributed the survey, returned anonymously. Data were
      analyzed using SPSS to identify differential responses by gender. Although HIV
      knowledge was high, perceived self-efficacy differed significantly by gender,
      with men describing themselves as less able to insist upon condom use (P <
      .00001). Men were also significantly more likely to report using drugs or alcohol
      in situations likely to lead to a sexual encounter (P < .001) and to having lower
      self-efficacy in relation to HIV protection than women in such situations (P <
      .02). Men were also significantly more likely to believe that monogamy obviates
      the need to use condoms (P < .01). A substantial number of men (13) and women
      (14.6) say they do not use condoms because they are protected from unwanted
      pregnancy by pill. Gender-specific HIV education and skills-building programs may
      improve the success of AIDS prevention efforts by confronting and addressing
      gender differences. The reliance on hormonal methods of birth control alone may
      be a barrier to condom use for both male and female adolescents and young adults.
      Medical Subject Headings (MeSH): AIDS; HIV; knowledge, attitudes, and practice;
      gender; condoms; birth control; family planning; teenage pregnancy.

PMID- 8874707
TI  - Translating public health research into public health practice: outcomes and
      characteristics of successful collaborations.
AB  - For over five years we have been involved in a series of collaborations between
      academic public health and state and local public health organizations. This
      article briefly describes the outcomes produced and under development by these
      collaborations and delineates and discusses some characteristics we now
      hypothesize will predict successful academic/practice collaboration. These
      collaborative projects with public health organizations in Alabama, Indiana, and
      New Mexico have produced outcomes that influenced the organization of the
      agencies and the allocation of resources within the agencies. The collaborations
      also have contributed to the body of literature concerning management processes
      in public health agencies and influenced the teaching of strategic management to
      students of health services. Our experiences and interactions led to the
      identification of 10 characteristics we believe predict successful academic and
      practice collaborations, discussed in three groups as (1) characteristics of
      successful academic collaborators, (2) characteristics of successful
      collaborating public health organizations, and (3) characteristics of successful
      collaborative projects.

PMID- 8874708
TI  - Immunosuppressive properties of monoclonal antibodies and human polyclonal
      alloantibodies to the R80K protein of trophoblast.
AB  - PROBLEM: The R80K protein on human trophoblast is antigenically polymorphic, and
      in all placentae of successful pregnancies, the protein is covered by maternal
      alloantibody. Alloantibody eluted from human placenta has been shown to inhibit
      killing by human NK cells. Do those antibodies to R80K that inhibit NK killing
      also affect the murine abortion models? METHODS: We made three murine monoclonal
      antibodies to conserved epitopes, on human R80K, all of which also reacted with
      the homologous murine molecule. One antibody only, BA11, suppressed NK
      cytotoxicity to K562 and of mouse spleen NK cells to murine trophoblast. All
      three were tested in mouse models of abortion: the CBA x DBA/2 model with a high
      resorption rate of F1 embryos compared with the parental strains, an endotoxin
      induced abortion/resorption model and a third model in which the pregnant mouse
      is subject to sonic stress. CONCLUSION: Those IgG antibodies eluted from
      microvesicles which bound to K562, and one of the three monoclonals, BA11,
      inhibited NK killing. The antibodies react with the murine molecule, and BA11
      inhibited abortion in all three mouse abortion models. This reinforces the thesis
      that interference with NK killing can influence abortion/resorption in mice, and
      the BA11 antibody may effect similar results in analogous human situations.

PMID- 8874709
TI  - Human autoantibodies recognizing human and mouse preimplantation stages.
AB  - PROBLEM: To find out whether autoantibodies against human preimplantation stages
      are present in some human sera and, if so, whether the antibodies could be
      capable to affect the egg development and/or to trigger an activation of the
      complement system at the procedures of assisted conception. METHODS: 1.
      Immunohistochemistry on blots of human preimplantation stages. 2.
      Immunohistochemistry on paraffin sections of human and mouse preimplantation
      stages. 3. Culture of mouse morulae to analyze complement activation. RESULTS: 1.
      Some human sera contained autoantibodies against human preimplantation stages. 2.
      Human-mouse cross-reacting antibodies against preimplantation stages occurred. 3.
      Immune complexes, formed on mouse preimplantation stages, activated the
      complement systems in egg cultures, resulting in a damaging of the eggs.
      CONCLUSION: The presence of natural autoantibodies to preimplantation stages may
      be associated with reproduction failure, caused by a direct effect by the
      autoantibodies and/or an activation of the uterine complement system by the
      immune complexes formed.

PMID- 8874710
TI  - Surface annexin II on placental membranes of the fetomaternal interface.
AB  - PROBLEM: The phospholipidbinding membrane protein annexin II has been
      demonstrated to possess FcR activity for IgG and has been localized to the outer
      part of the syncytiotrophoblast cell layer. The question has arisen whether
      annexin II is exposed on the surface of syncytiotrophoblast cells thus enabling
      it to take part in the transport of IgG across the maternal barrier. METHOD:
      Syncytiotrophoblast microvillous plasma membranes were analyzed by flow cytometry
      for annexin II as well as established surface molecules. Fresh, fixed placental
      tissue was preincubated with antibodies to annexin II or known trophoblast
      surface molecules, and analyzed by confocal laser scanning microscopy. RESULTS:
      Annexin II and its subunit p11 were expressed on the surface of the
      syncytiotrophoblast microvillous plasma membranes as were other established
      surface proteins (CD46, CD59, placental alkaline phosphatase), using both flow
      cytometry and confocal microscopy. Annexin was not detected on the surface of
      viable cultured trophoblast cells. CONCLUSION: Annexin II is exposed on the
      surface of syncytiotrophoblast cells as a heterotetramer together with its light
      chain p11. It is exposed to maternal blood and may be instrumental in IgG
      transport across the placental barrier by binding.

PMID- 8874711
TI  - Effects of products of activated immune cells and recombinant cytokines on
      spontaneous and ionophore-induced acrosome reaction.
AB  - PROBLEM: The purpose of this study was to examine whether the products of
      activated immune cells influence spontaneous and ionophore-induced sperm acrosome
      reaction. METHOD: The spontaneous and ionophore-induced acrosome reaction were
      evaluated by staining with fluorescein isothiocyanate (FITC) Pisum sativam
      agglutinin after incubation in capacitating media supplemented with either
      supernatants from Con-A activated leukocyte cultures or human recombinant (r) IL
      1 beta, TNF-alpha, and INF-gamma. RESULTS: The supernatants from Con A-activated
      peripheral blood leukocyte cultures at 1:1 and 1:10 dilution significantly
      increased the rate of spontaneous acrosome reaction (P < 0.001 and P < 0.01).
      Along with displayed abnormally elevated levels of spontaneous acrosome loss,
      sperm cells showed an insufficient ability to undergo acrosome reaction in
      response to the ionophore treatment. Recombinant IL-1 beta at increasing
      concentrations from 30 to 3 x 10(4) U/ml did not have an effect on spontaneous
      and ionophore-induced acrosome reaction. In contrast, spermatozoa that underwent
      capacitation in media with 7 x 10(3), 7 x 10(4), and 7 x 10(5) U/ml of rINF-gamma
      showed a significant increase in spontaneous and induced acrosome reaction
      compared to the control (P < 0.001). Recombinant TNF-alpha at concentrations of
      3.5 x 10(3) U/ml and 3.5 x 10(4) U/ml significantly inhibited ionophore-induced
      acrosome reaction (P < 0.001). Both rINF-gamma and rTNF-alpha together revealed
      an effect on the acrosome reaction similar to Con-A generated supernatants (1:1
      and 1:10 dilution) only at the highest concentrations. CONCLUSIONS: Some cases of
      infertility may result from a defective acrosome reaction (premature acrosome
      loss or insufficient acrosome response to the stimulants) caused by products of
      activated lymphocytes and macrophages that are released into the male and female
      reproductive tracts.

PMID- 8874712
TI  - Cytokines of the human reproductive tract.
AB  - PROBLEM: How is it possible that the female genital tract immunologically does
      not reject spermatooa not the preimplantation and nidating embryo? METHODS: Four
      fluids of the human reproductive tract, i.e., human oviductal fluid (hOF),
      follicular fluid (FF), amniotic fluid (AF), and seminal plasma (SP) were
      investigated by specific ELISA for 18 cytokines. The concentrations, presence or
      absence of these compounds were evaluated for their possible role in the
      immunology of the reproductive process. RESULTS: Stem cell factor and IL-11 were
      detected in all reproductive tract fluids examined whereas large amounts of IL-1
      beta and IL-1RA was found in AF and hOF. Follicular fluid revealed IL-2. HOF
      contained IL 2, IL-6, IL-8, TNF-alpha, MIP-1 alpha, IFN-gamma, and high levels of
      IL-1 beta, IL-10, IL-1RA, and sIL-2R. Amniotic fluid contained sIL-2R, IL-8, IL-1
      beta, IL-1RA, IL-6, TNF-alpha, and MIP-1 alpha. No IL-12 or IL-13 was detected in
      hOF follicular fluid or amniotic fluid. Almost no free TGF-beta 1 or TGF-beta 2
      was found in any reproductive tract fluid except seminal plasma. Seminal plasma
      contained large quantities of free TGF-beta 1 (9,220 +/- 3,635 pg/mL) in addition
      to large quantities of latent TGF-beta 2 (2,933 +/- 2,169 pg/mL) and TGF-beta 1
      (71,000 +/- 3,240 pg/mL). Furthermore, considerable concentrations of IL-8 (1900
      +/- 374 pg/mL) and sIL-2R (350 mu/mL) exist in seminal plasma. CONCLUSIONS: HOF
      contains a high level of IL-10 (588 +/- 304 pg/mL), a powerful immune suppressor
      which probably plays a role in regulating immune responses in the fallopian tube
      and possibly in the endometrial cavity. Our observations suggest that seminal
      plasma with its huge content of TGF beta provides immune protection for sperm.
      Unfortunately, such high concentrations of TGF beta may also inhibit an immune
      defense in any organ in which semen is deposited.

PMID- 8874713
TI  - Effect of immunization with human SP-10 in male rodents.
AB  - PROBLEM: Over the years immunocontraception has emerged as a promising modality.
      Theoretically it is possible to intercept fertility using a panel of antigens
      expressed along the entire pituitary, hypothalamus and gonadal axis. One such
      sperm antigen designated as SP-10 is in advanced stages of development. Its gene
      has been cloned by Wright et al. (Biol Reprod 1990; 42:693-701). It is envisaged
      that immunization with SP-10 would induce antisperm antibodies in females and
      hence interrupt fertility. However, the in vivo effect of SP-10 immunization has
      been assessed in male rodents with particular reference to spermatogenesis and
      effect of such immunization in various tissues. The SP-10 antigen was a generous
      gift from Dr. John Herr. METHODS: A group of male Wistar rats and BALB/c mice
      were immunized with a total dose of 175 micrograms of SP-10 glutathione
      transferase fusion protein. Anti-SP-10 antibodies generated were detected by
      ELISA, immunofluorescence, flow cytometry and western blot assay. Histopathology
      of all the organs was conducted with particular reference to assess their effect
      on sperm maturation in testicular sections. RESULTS: All the animals immunized
      with SP-10 depicted a significant antibody response. DNA analysis by flow
      cytometry did not reveal any arrest of spermatogenesis, which was confirmed by
      histological studies. CONCLUSIONS: It is concluded that conventional immunization
      generating significant antibody titers does not induce arrest of spermatogenesis
      in male rodents.

PMID- 8874714
TI  - Quantitative changes in macrophage distribution in normal mouse ovary over the
      course of the estrous cycle examined with an image analysis system.
AB  - PROBLEM: The current study considered the distribution of macrophages within the
      major ovarian structures throughout the estrous cycle. METHODS:
      Immunohistochemical analyses were carried out using an avidin-biotin-peroxidase
      staining method and the rat anti-mouse macrophage monoclonal antibody anti-Mac-l
      was applied to stain macrophages. A computer-assisted image analysis system was
      used to quantify and compare the distribution of macrophages within individual
      ovarian structures during the estrous cycle. The following morphological
      structures were analyzed: primordial, preantral, antral, pre-Graafian, and
      atretic follicles; first-, second-, and third-generation corpora lutea; and the
      interstitium. The analysis included follicular and corpus luteum substructures:
      theca, granulosa cells, and interstitium. The system allows the estimation of
      macrophage distribution as a macrophage density per microns2 of the defined area.
      RESULTS: Primordial and preantral follicles did not contain macrophages during
      all stages of the estrous cycle. In antral, pre-graafian, and graafian follicles,
      macrophages were located and quantified only in the theca and were not detected
      in the granulosa cell layer. In contrast, atretic follicles showed macrophage
      localization in both thecal and granulosa cell layers. Macrophages were present
      in small numbers in the granulosa luteal cell layer and in high numbers in the
      thecal layer of newly developing corpora lutea. In the second generation of
      corpus luteum, macrophages followed the same pattern of distribution, while old
      corpora lutea contained significantly higher numbers of macrophages in both
      thecal and luteal cell layers. Surprisingly, significant quantitative changes in
      the macrophages distribution were detected over the course of the estrous cycle.
      Macrophage density was significantly higher in proestrus and metestrus when
      compared with the density in diestrus and estrus in most of the studied
      substructures with the exception of atretic follicles. Atretic follicles showed
      high macrophage density throughout the cycle with a two-fold higher density at
      metestrus. CONCLUSION: Macrophages were present in the mouse ovary over the
      course of the estrous cycle. The greatest numbers of macrophages appearing in
      corpora lutea and in atretic follicles suggest a role for macrophages in corpus
      luteum differentiation and follicular atresia. Their patterns of distribution at
      proestrus and metestrus within microenvironmental compartments suggests a
      functional correlation with the events of ovarian development.

PMID- 8874715
TI  - Susceptibility of equine chorionic girdle cells to lymphokine-activated killer
      cell activity.
AB  - PROBLEM: Equine chorionic girdle cells are a subpopulation of highly invasive
      trophoblast cells that attach and invade the uterine epithelium on Day 35 (Day 0
      = day of ovulation). These invading chorionic girdle cells form endometrial cups
      that are associated with a marked local maternal leukocytic response that may
      result in the demise of the cups at Day 120 of pregnancy. Once endometrial cups
      become established in the uterine wall they do not express MHC antigens, and
      therefore may only be susceptible to non-MHC restricted cytotoxic cells. The
      susceptibility of cultured chorionic girdle cells to LAK cell cytotoxicity was
      tested in order to evaluate the role of this type of cytotoxicity in the life
      cycle of endometrial cup tissue. METHODS: Chorionic girdle cells from ten Day 34
      conceptuses were collected, cultured, and used as a target cell in a lymphokine
      activated killer assay to determine if these cells were susceptible to lymphokine
      activated killing. RESULTS: Cultured chorionic girdle cells demonstrated similar
      in vitro morphological features and patterns of antigen expression to those seen
      in vivo in endometrial cups. Cultured chorionic girdle cells were susceptible to
      lymphokine activated killing. CONCLUSIONS: Lymphokine activated killer cells may
      play a role in the degeneration of endometrial cup tissue. The potential
      mechanisms of regulation of uterine LAK cell activity in the horse are discussed.

PMID- 8874716
TI  - Effect of nasal occlusion on tracheal and pharyngeal pressures in horses.
AB  - OBJECTIVE: To compare tracheal and pharyngeal inspiratory and expiratory
      pressures achieved during 60 seconds of nasal occlusion in standing horses with
      pressures achieved in horses during intense exercise. ANIMALS: 5 Standardbreds.
      PROCEDURE: Tracheal and pharyngeal inspiratory and expiratory pressures were
      obtained from 5 horses during 60 seconds of nasal occlusion and compared with
      tracheal and pharyngeal pressures achieved during incremental treadmill exercise
      tests in which horses ran at 50, 75, and 100% of the speed that resulted in
      maximal heart rate (HRmax). RESULTS: Significant difference was not detected
      between peak tracheal inspiratory pressure during nasal occlusion and peak
      tracheal inspiratory pressure at HRmax Peak pharyngeal inspiratory pressure was
      significantly more negative, and peak tracheal and peak pharyngeal expiratory
      pressures were significantly more positive during 60 seconds of nasal occlusion
      than those observed in horses running at HRmax. CONCLUSION: During upper airway
      endoscopy in standing horses, 60-second nasal occlusion induced tracheal and
      pharyngeal inspiratory pressures that equaled or exceeded pressures achieved
      during high-intensity exercise. CLINICAL RELEVANCE: Nasal occlusion is useful to
      simulate upper airway pressures achieved during high-intensity exercise.

PMID- 8874717
TI  - Maintenance of equine articular cartilage explants in serum-free and serum
      supplemented media, compared with that in a commercial supplemented medium.
AB  - OBJECTIVE: To evaluate the effects of a commercially defined, serum-free medium
      additive on equine articular cartilage explants, compared with effects of serum
      free and serum-supplemented media. ANIMALS: Articular cartilage from a 3-year
      old, mixed breed horse euthanatized for reasons other than musculoskeletal
      disease or sepsis. PROCEDURE: Media were changed every 48 hours, and the
      glycosaminoglycan (GAG) content was determined in media collected at each time
      point. Glycosaminoglycan synthesis by explant chondrocytes, and residual GAG
      content of articular cartilage (as a measure of explant GAG loss) were determined
      at the end of the study (day 8). RESULTS: Articular cartilage explants in serum
      free medium and the commercial supplemented medium had significantly lower GAG
      synthesis and GAG content than did those incubated in serum-supplemented medium.
      There were no significant differences in GAG synthesis and content between serum
      free and commercial supplemented medium groups. When comparing medium GAG content
      for all treatment groups, the GAG content in serum-free medium on day 8 was
      significantly greater than that in commercial supplemented medium, but
      significant differences were not evident in percentage of release of GAG (as an
      indicator of GAG degradation) among all 3 treatment groups. CONCLUSIONS:
      Commercial supplemented medium had effects on articular cartilage matrix GAG loss
      into medium equal to those of serum-supplemented medium (eg, both lost articular
      cartilage explant GAG to a similar degree). However, residual articular cartilage
      GAG content was higher in serum-supplemented medium, as was GAG synthesis.
      Commercial supplemented medium appears to either lack the proper ingredients to
      maintain steady-state GAG synthesis, or lacks proper concentrations of these
      ingredients.

PMID- 8874718
TI  - Sonographic observations of the gastroduodenal junction of dogs.
AB  - OBJECTIVES: To determine the sonographic dimensions and an imaging protocol for
      the pyloric region of the normal canine stomach, and whether sonography could be
      used to demonstrate antroduodenal motility. ANIMALS: 20 clinically normal, mixed
      breed dogs (mean +/- SD, 15.1 +/- 7.1 kg). PROCEDURE: In vitro sonographic
      observations of the gastroduodenal junction were made after each had been mounted
      on an acrylic rack placed in an organ bath. The in vivo studies were performed in
      anesthetized dogs. RESULTS: The wall of the pyloric antrum was 4 to 5 mm thick,
      that of the pylorus was 3 to 4 mm thick, and that of the cranial part of the
      duodenum was 2 to 3 mm thick. The pyloric canal had a length of 16 to 17 mm and
      overall in vivo diameter of 22 mm, and the muscular part of its wall was 2 to 3
      mm thick. In vivo sonographic images were best made with the dog in dorsal
      recumbency, tilted 30 degrees to the right-the feasibility study clearly
      demonstrated the form and function of antroduodenal motility, including gastric
      and duodenal peristalsis, opening and closing of the pyloric canal, and
      duodenogastric reflux of fluid and gas. CONCLUSIONS AND CLINICAL RELEVANCE: The
      use of a routine imaging protocol, accompanied by mensuration of the
      gastroduodenal junction, will permit an opinion to be given as to whether the
      structure and function of the region are normal or whether pathologic change
      exists.

PMID- 8874719
TI  - Ultrastructure of selected struvite-containing urinary calculi from dogs.
AB  - OBJECTIVE: To elucidate the ultrastructural details of struvite-containing
      urinary calculi from dogs. SAMPLE POPULATION: 38 specimens were selected from a
      collection of approximately 13,000 canine urinary calculi: 18 of these were
      composed entirely of struvite, and 20 consisted of struvite and calcium phosphate
      (apatite). PROCEDURE: Qualitative and quantitative analyses of specimens included
      use of plain and polarized light microscopy, x-ray diffractometry, scanning
      electron microscopy with backscattered electron imagery, x-ray fluorescence
      scans, and electron microprobe analysis. RESULTS: 4 textural types were
      recognized among struvite calculi, and 4 textural types of struvite-apatite
      calculi were described. Evidences of calculus dissolution were described from 4
      calculi studied. CONCLUSIONS: The presence of small, well interconnected primary
      pores in struvite-containing urinary calculi from dogs appears to be a
      significant factor in determining the possible interaction of calculi with
      changes in the urine composition. The progress of dissolution from the calculus
      surface to the calculus interior appears to be largely affected by the primary
      porosity originally present between crystals forming the calculus framework.
      Apatite was observed to be more resistant to dissolution than struvite. CLINICAL
      RELEVANCE: The prevalence of fine concentric laminations having low porosity, and
      the common occurrence of apatite among struvite-containing urinary calculi from
      dogs may be 2 reasons why the efficacy of dietary and medicinal manipulations in
      dissolving urinary calculi is greater among cats than it is among dogs.

PMID- 8874720
TI  - Temporal variation and factors affecting measurement of canine von Willebrand
      factor.
AB  - OBJECTIVE: To determine whether canine plasma von Willebrand factor (vWf) varies
      between and within individuals over time and with different blood sample
      collection and processing procedures. ANIMALS: 26 adult dogs and 6 pups.
      PROCEDURE: Blood was obtained from the jugular or cephalic vein daily for 8 to 19
      days and weekly for 9 to 23 weeks in adult dogs and periodically up to 180 days
      of age in pups. Temporal variation in vWf concentration and the effect of
      vascular occlusion, venipuncture site, lipemia, hemolysis, anticoagulant, storage
      time, freeze-thawing, and centrifugation speed on plasma vWf concentration,
      measured by ELISA, were determined. RESULTS: Plasma vWf concentration varied over
      time. In dogs with mean vWf concentration > or = 79 U/dl, the largest
      intraindividual range in vWf spanned 64 U/dl with daily and 53 U/dl with weekly
      sample collection. In dogs with mean vWf concentration < or = 24 U/dl, the
      largest individual variation was 12 U/dl with daily and weekly sample collection.
      In dogs with mean vWf concentration > or = 53 and < or = 74 U/dl, the largest
      intraindividual range spanned 35 U/ dl. Mean vWf concentration of pups from 3 to
      180 days of age did not change. Sample hemolysis decreased mean vWf by 37%. Mean
      vWf concentration was 9% higher in cephalic than jugular vein samples (P =
      0.056). Other sample collection/preparation procedures did not affect vWf
      concentration. CONCLUSION: There was substantial temporal variation in vWf
      concentration within individual dogs. CLINICAL RELEVANCE: Multiple tests may be
      necessary to obtain a reliable estimate of vWf concentration in dogs.

PMID- 8874721
TI  - Inter- and intraindividual variability of the response to intravenous glucose
      tolerance testing in cats.
AB  - OBJECTIVE: To evaluate inter- and intraindividual variation in results of the
      intravenous glucose tolerance test in cats. ANIMALS: 19 healthy specific-pathogen
      free-derived cats were allotted to group A (n = 13), which was accustomed, and
      group B (n = 6), which was unaccustomed to having blood drawn. PROCEDURE: Blood
      samples were collected for glucose and insulin assays before and 5, 10, 15, 30,
      45 and 60 minutes after i.v. administration of 500 mg of dextrose/kg of body
      weight. Glucose half-life (t1/2) and disappearance co-efficient (K), and the
      acute-phase insulin response (Ins0-10) were calculated. Inter- and
      intraindividual variability was assessed by calculating the coefficient of
      variation for test variables. RESULTS: Comparing the 2 tests, there were no
      significant differences in glucose and insulin concentrations prior to dextrose
      administration or in t1/2, K, or Ins0-10. However, compared with group-A cats,
      cats in group B had significantly (P < 0.05) longer t1/7 and lower K and Ins0-10
      values, which was attributed to increased stress in these cats. Overall, the
      interindividual variability was 62.8% for K, 54.6% for t1/2, and 76.0% for Ins0
      10. Mean intraindividual variability was 32.0 (range, 0.1 to 72.0)% for K and
      t1/2, and 45.8 (range, 4.0 to 179.5)% for Ins0-10. There was only a moderate
      correlation in results between the 2 tests (rs = 0.59 for t1/2 and K, rs = 0.58
      for Ins0-10). CONCLUSION: The variability in results of intravenous glucose
      tolerance tests in cats suggests caution is necessary in interpreting results of
      a single test in individuals.

PMID- 8874722
TI  - Effects of serum separation tubes on serum benzodiazepine and phenobarbital
      concentrations in clinically normal and epileptic dogs.
AB  - OBJECTIVE: To characterize the effects of serum separation tubes (SST) on serum
      drug concentrations. SAMPLE POPULATION: Clinically normal dogs (clorazepate, n =
      7) or dogs with epilepsy (phenobarbital, n = 7) were studied in experiment 1, and
      samples submitted for therapeutic drug monitoring (n = 87) were studied in
      experiment 2. PROCEDURE: In experiment 1, blood containing either drug was placed
      in 2 types of 4-ml SST (SST-A and SST-B) and in nonserum separation tubes (non
      SST [control]). Samples were processed, then stored at 20 to 22 C (both drugs) or
      10 C (phenobarbital only). Aliquots were collected for 96 hours. The rate
      constant of disappearance and the percentage decrease of each drug over time were
      determined for each tube. For experiment 2, paired samples were collected in non
      SST and SST and submitted by mail for therapeutic drug monitoring. The SST
      samples were either decanted from SST prior to shipment (group 1; n = 30) or
      mailed in SST with serum in contact with the silica gel (group 2; n = 57). Drug
      concentrations and drug elimination half-life were compared between groups. For
      both experiments, drugs were detected in samples, using polarized
      immunofluorescence. RESULTS: For experiment 1, the rate constant of drug
      disappearance for both drugs was greater in the 4-ml SST-A (P < 0.0001). This SST
      also caused the greatest percentage decrease (20% for phenobarbital and 35% for
      benzodiazepines) at 96 hours. Refrigeration reduced the mean decrease in
      phenobarbital at 96 hours to 11%. For experiment 2, phenobarbital concentration
      was lower for both SST, compared with non-SST (P < 0.0005). Phenobabital had
      decreased a mean 6.4 +/- 0.5% in group-1 and a mean 30.5 +/- 11.1% in group-2 (P
      < 0.0005) samples. CONCLUSION: The SST should be avoided when collecting serum
      for monitoring of either phenobarbital or benzodiazepines. CLINICAL RELEVANCE:
      The SST can falsely decrease serum drug concentrations and should be avoided when
      collecting blood for therapeutic drug monitoring.

PMID- 8874723
TI  - Laboratory reference values for a group of captive Ball Pythons (Python regius)
AB  - OBJECTIVE: Laboratory reference values, including hematologic and serum
      biochemical variables, and oropharyngeal bacteria flora, were determined in a
      group of captive Ball Pythons (Python regius). ANIMALS: 20 adult Ball Pythons,
      weighing between 700 and 1,510 g, were allowed to acclimate at the recommended
      temperature range for the species (25 C night-time, up to 30 C daytime), then
      were evaluated for internal parasites and treated with appropriate medication
      prior to the start of the study. PROCEDURE: Hematologic values determined
      included WBC, hemoglobin, hematocrit, plasma protein, and differential cell
      count. Clinical biochemical analysis included determination of glucose, uric
      acid, calcium, phosphorus, total protein, alanine transaminase, alkaline
      phosphatase, and aspartate transaminase values. In addition to blood values,
      oropharyngeal swab specimens of the mouth were submitted for culture to determine
      the species of bacteria found in this population. Descriptive statistics were
      calculated for each hematologic and clinical biochemical value. Mean, SEM, and
      ranges were calculated. RESULTS: Hematologic values were similar to those
      reported in other snake species, except the hematocrit, which was lower. Clinical
      biochemical values different from those of other species were alkaline
      phosphatase activity, which was lower, and calcium and phosphorus concentrations,
      which were lower than values in other species. Bacteria isolated from the
      oropharynx were principally gram-negative organisms. CONCLUSION: Reference
      intervals reported in this study are important for establishing a database for
      comparative studies of Ball Pythons in other locations and under different
      husbandry conditions. CLINICAL RELEVANCE: Accumulated laboratory reference values
      will assist veterinarians in assessing the health status of Ball Pythons.

PMID- 8874724
TI  - Effect of antibodies to staphylococcal alpha and beta toxins and Staphylococcus
      aureus on the cytotoxicity for and adherence of the organism to bovine mammary
      epithelial cells.
AB  - OBJECTIVE: To determine the effect of antibodies to staphylococcal alpha and beta
      toxins and Staphylococcus aureus on the toxicity for and adherence of S aureus to
      bovine mammary epithelial cells. SAMPLE POPULATION: Cultured bovine mammary
      epithelial cells and Staphylococcus aureus obtained from a cow with mastitis.
      PROCEDURE: Cultured bovine epithelial cells were incubated with antisera to alpha
      and beta toxins of S aureus and culture supernatant; cell damage and S aureus
      adherence to cells were measured. RESULTS: Antisera to alpha, beta, and alpha +
      beta toxins inhibited cytotoxicity of S aureus culture supernatant. Antiserum to
      alpha + beta toxin was the most effective inhibitor of cytotoxicity and antiserum
      to beta toxin was the least effective. All 3 antisera decreased the percentage of
      S aureus adhered to the mammary epithelial cell monolayers and numbers of
      organisms per cluster of adhered bacteria. In this study, antisera to alpha and
      alpha + beta toxins decreased the number of S aureus clusters per dish, but
      antiserum to beta toxin had no significant effect. Antiserum to alpha + beta
      toxin decreased the percentage of epithelial cells with adhered S aureus, but
      neither antiserum to alpha nor beta toxin had significant effect. Antiserum to S
      aureus decreased the percentage of S aureus adhered, number of clusters perdish,
      number of organisms per cluster, and percentage of epithelial cells with S aureus
      adhered. CONCLUSIONS: Antibodies to staphylococcal alpha and beta toxins inhibit
      adherence to and cytotoxicity of S aureus for bovine mammary epithelial cells,
      and antibodies to S aureus inhibit adherence of S aureus to bovine mammary
      epithelial cells.

PMID- 8874725
TI  - Regulation of activation of bovine neutrophils by aggregated immunoglobulin G.
AB  - OBJECTIVES: To investigate the role of extracellular Ca2+ and Mg2+ in aggregated
      IgG (aIgG)-mediated cellular activation, and to determine how aIgG-induced
      activation is coupled to Ca2+ homeostasis in bovine neutrophils. SAMPLE
      POPULATION: 4 clinically normal, lactating Holstein cows, in their second
      lactation, which ranged between 60 and 150 days. PROCEDURE: aIgG was prepared by
      heating bovine IgG, and C5a was obtained by activating fetal bovine serum with
      zymosan. Luminol-amplified chemiluminescence (CL) of isolated neutrophils was
      measured in the presence of aIgG or phorbol 12-myristate 13-acetate (PMA). The
      reaction mixture contained either Hanks' balanced salt solution or Ca(2+)- and
      Mg(2+)-free Hanks' balanced salt solution. Binding of aIgG to neutrophils was
      measured by flow cytometry after incubation with fluorescein isothiocyanate
      conjugated second antibody. Intracellular-free concentration [Ca2+]i was measured
      in a fluorescence spectrofluorometer after incubation of neutrophils, loaded with
      the fluorescent dye fura-2 acetoxymethyl ester, with either aIgG or C5a. RESULTS:
      In a Ca(2+)- and Mg(2+)-containing reaction mixture, aIgG induced strong CL
      responses, whereas removal of extracellular divalent cations almost abolished the
      respiratory burst activity. The CL emission on stimulation with PMA was
      independent of extracellular Ca2+ and Mg2+. Examination of cells by flow
      cytometry after incubation with aIgG indicated that the binding of aIgG was
      identical in the presence and absence of extracellular Ca2+ and Mg2+. No increase
      in [Ca2+]i was seen in fura-2 acetoxymethylester-loaded neutrophils after
      stimulation with aIgG. C5a induced a typical transient increase in [Ca2+]i.
      CONCLUSIONS: aIgG-induced activation of bovine neutrophils is highly dependent on
      presence of extracellular divalent cations. This dependency is not caused by the
      need of divalent cations for binding of aIgG by neutrophils or because the influx
      of Ca2+ from the extracellular space is an integral component of aIgG-mediated
      activation pathway. Because need for extracellular Ca2+ and Mg2+ could be
      partially circumvented by pretreating neutrophils with PMA, it is possible that
      this activation pathway may involve a protein kinase C, which is not directly
      coupled to receptors for aIgG.

PMID- 8874726
TI  - Respiratory tract disease and mucosal colonization by Pasteurella haemolytica in
      transported cattle.
AB  - OBJECTIVES: To follow incidence of Pasteurella haemolytica (PH) in the upper
      respiratory tract of healthy calves at the farm and through the marketing
      process, and to determine the effect of vaccination on PH colonization of the
      upper respiratory tract and on the incidence of respiratory tract disease (RTD).
      ANIMALS: 2- to 5-month-old calves (n = 104) from 4 farms. PROCEDURE: Calves were
      vaccinated with a killed PH serotype-1 product. Nasal secretion and tonsil wash
      specimens were cultured for PH, and serum antibody was measured by indirect
      hemagglutination. Calves with RTD were treated with tilmicosin phosphate.
      RESULTS: At the feedyard, 73 calves had RTD. The incidence of RTD was
      significantly related to the farm of origin, and was inversely related to the PH
      serum titer at the farm, but was not influenced by vaccination. Isolations of PH
      serotype 1, however, were reduced by vaccination. The major serotypes of PH
      encountered were 1 and 6. CONCLUSION: Vaccination can reduce the frequency of
      colonization of the upper respiratory tract by PH.

PMID- 8874727
TI  - Effect of anesthesia and surgery on energy expenditure determined by indirect
      calorimetry in dogs with malignant and nonmalignant conditions.
AB  - OBJECTIVE: To determine energy expenditure (EE) of apparently resting, client
      owned dogs with malignant or nonmalignant diseases that were recovering from
      anesthesia and surgery, and compare those values with values from clinically
      normal, apparently resting, client owned dogs. ANIMALS: 40 apparently resting,
      client-owned dogs that had been given general anesthesia for various elective and
      nonelective surgical procedures, and 30 apparently resting, clinically normal
      client-owned dogs used as controls. PROCEDURE: EE was determined, using an open
      flow indirect calorimetry system. Each dog was evaluated before and after surgery
      (0, 1, 2, and 3 days after surgery, then at suture removal > 14 days later) and
      compared with apparently resting, clinically normal, client-owned dogs (n = 30).
      Parameters evaluated were rate of oxygen consumption (Vo2/kg of body weight:
      ml/min/kg; Vo2/kg0.75: ml/min/kg0.75), EE (EE/kg: kcal/kg/d; EE/kg0.75:
      kcal/kg0.75/d), and respiratory quotient. RESULTS: Surgery and anesthesia did not
      significantly alter any of these parameters at any time assessed in any group.
      The pretreatment Vo2 and EE were significantly lower in the dogs with cancer,
      compared with dogs of other groups. CONCLUSIONS: These data suggest that the EE
      of a restricted group of dogs that undergo anesthesia and surgery for malignant
      and nonmalignant conditions does not increase from baseline values or when
      compared with values in clinically normal, client-owned dogs. CLINICAL RELEVANCE:
      This information may be of value when planning nutritional treatment for dogs
      recovering from anesthesia and surgery.

PMID- 8874728
TI  - Toxoplasma gondii antigen recognition by serum immunoglobulins M, G, and A of
      queens and their neonatally infected kittens.
AB  - OBJECTIVE: To evaluate antigen recognition patterns of serum IgM, IgG, and IgA
      from queens and their kittens as a method of diagnosing neonatal toxoplasmosis.
      ANIMALS: 5 pregnant queens were inoculated orally with Toxoplasma gondii tissue
      cysts during gestation (18 to 44 days). On various days after parturition (0 to
      97), serum was obtained from queens and kittens (n = 19). PROCEDURE: Tissues from
      most kittens were assessed for T gondii infection by bioassay in mice. Serum
      samples were evaluated by IgM, IgG, and IgA western blot immunoassays for the
      presence of T gondii antibodies. Antigens recognized by kitten serum samples, but
      not by the corresponding queen serum sample, were considered to indicate neonatal
      infection with T gondii. RESULTS: Using the results of western blot immunoassay,
      8 of 19 kittens (age, 2 to 97 days) were determined to be infected with T gondii.
      Western blot immunoassay results correlated well with bioassay results,
      identifying 7 of 8 bioassay-positive kittens. Western blot immuno-assay
      additionally identified 1 kitten as infected, but tissues from the kitten had not
      been bioassayed. In each of the 5 kittens that developed clinical signs of
      toxoplasmosis, the diagnosis of neonatal toxoplasmosis was supported by results
      of the western blot immunoassays. CONCLUSION AND CLINICAL RELEVANCE: Comparison
      of queen and kitten T gondii antigen recognition patterns of IgM, IgG, and IgA
      can be used for antemortem diagnosis of neonatal toxoplasmosis.

PMID- 8874729
TI  - Effect of progesterone on prostaglandin F2 alpha secretion and outcome of
      pregnancy during cloprostenol-induced abortion in mares.
AB  - OBJECTIVES: To determine the role of progesterone in the regulation of endogenous
      prostaglandin F2 alpha (PGF2 alpha) secretion during cloprostenol-induced
      abortion and to investigate use of progestins to prevent prostaglandin-associated
      abortion. ANIMALS: 16 pregnant mares. PROCEDURE: To induce abortion, cloprostenol
      (250 micrograms/d) was administered daily until fetal expulsion or for up to 5
      days. In experiment 1, 8 mares, 98 to 153 days' pregnant, received progesterone
      (300 mg/d) at 24-hour intervals for 5 days, starting 18 hours after the first
      cloprostenol administration. In experiment 2, 8 mares, 93 to 115 days' pregnant,
      received altrenogest (44 mg/d) at 24-hour intervals, starting 12 hours after the
      first cloprostenol administration. Historic control mares, 82 to 102 days'
      pregnant, received cloprostenol (250 micrograms/d) daily until fetal expulsion.
      RESULTS: In control mares, fetal expulsion occurred after 2 to 3 cloprostenol
      administrations and was associated with significant increases in PGF2 alpha
      secretion. Abortion did not occur in 5 of 8 progesterone-treated mares and 8 of 8
      altrenogest-treated mares, and endogenous PGF2 alpha secretion was inhibited,
      compared with values in aborting mares. CONCLUSION: Circulating progestogen
      concentrations may have a role in the outcome of pregnancy during prostaglandin
      induced abortion. Altered prostaglandin secretion may be a reflection of a direct
      effect of progesterone or may be caused by the abortion process. CLINICAL
      RELEVANCE: Progestogens might be useful for prevention of abortion in mares in
      which pregnancy is at risk owing to diseases that are associated with excess
      prostaglandin secretion.

PMID- 8874730
TI  - Comparison of antinociceptive, cardiovascular, and respiratory effects, head
      ptosis, and position of pelvic limbs in mares after caudal epidural
      administration of xylazine and detomidine hydrochloride solution.
AB  - OBJECTIVE: To examine and compare effects of 2 alpha 2-adrenergic receptor
      agonists, xylazine and detomidine, administered into the sacrococcygeal epidural
      space to induce safe and effective perineal analgesia on cardiovascular and
      respiratory functions, head ptosis, and position of pelvic limbs in healthy
      mares. ANIMALS: 8 healthy mares. PROCEDURE: Blood samples were drawn and systemic
      hemodynamics were determined, including cardiac output and pulmonary arterial,
      systemic arterial, and right atrial pressures. Two-way ANOVA with repeated
      measures was used to detect significant (P < 0.05) differences between mean
      scores of perineal analgesia, cardiorespiratory variables, head ptosis, and
      position of pelvic limbs in mares before and during a 3-hour testing period.
      Analgesia was determined by lack of sensory perception to electrical stimulation
      at the perineal dermatome and no response to needle prick stimulation in
      dermatomes extending from the coccyx to T15. Avoidance responses to electrical
      current and needle prick stimulation and behavioral changes (head ptosis,
      position of pelvic limbs) were quantitatively assessed by use of a scoring
      system. RESULTS: Epidurally administered xylazine induced perineal analgesia and
      variable bilateral caudal analgesia extending from the coccyx to S3 dermatome,
      with minimal cardiovascular and respiratory depression, head ptosis, changes in
      position of pelvic limbs, and no urination in standing mares. Epidurally
      administered detomidine induced perineal analgesia, variable bilateral analgesia
      with dermatomal spread ranging from coccyx to S3 and coccyx to T15, with
      cardiovascular depression, marked head ptosis, changes in position of pelvic
      limbs, and diuresis in standing mares. Onset of perineal analgesia after xylazine
      and detomidine administrations was 13.1 +/- 3.7 and 12.5 +/- 2.7 minutes (mean +/
      SD), respectively. The period of perineal analgesia was significantly (P < 0.05)
      longer in mares after epidural xylazine administration than after epidural
      detomidine administration (165 to > 180 minutes vs 160 +/- 8 minutes).
      CONCLUSIONS: Caudal epidurally administered xylazine (0.25 mg/kg of body weight
      in 8 ml of 0.9% NaCl) offers the most desirable conditions in mares: long-term
      perineal analgesia (> 2.5 hours), with minimal cardiopulmonary depression, head
      ptosis, changes in pelvic limb position, and no urination in standing mares
      during a 3-hour test period.

PMID- 8874731
TI  - Characterization of polypeptides synthesized and secreted by oviductal epithelial
      cell explants obtained from young, fertile and aged, subfertile mares.
AB  - OBJECTIVE: To compare the electrophoretic patterns of proteins synthesized and
      secreted by oviductal epithelial cell (OEC) explants obtained from young, fertile
      and aged, subfertile mares. ANIMALS: Young, fertile (n = 5; 2 to 7 years old) and
      aged, subfertile (n = 5; 17 to 24 years old) mares. PROCEDURE: 2-dimensional
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and computerized
      densitometry. RESULTS: Variation in the synthesis and secretion of polypeptides
      from young, fertile mare OEC (YOEC) and aged, subfertile mare OEC (AOEC) was
      evidenced by differences in the intensity of radiolabeled polypeptides on
      fluorograms. Fluorograms for 9 acidic (isoelectric point, 5.09 to 6.50) proteins
      of low to medium molecular mass (18.2 to 85.0 kd) from YOEC had greater intensity
      than did those from AOEC. Fluorograms for 7 proteins (10.5 to 45.0 kd;
      isoelectric point, 5.80 to 6.92) from AOEC had greater intensity. CONCLUSION: The
      differences detected in the fluorographic intensities of secreted proteins from
      YOEC and AOEC may be related to the disparity in embryo development observed
      between young, fertile and aged, subfertile mares. CLINICAL RELEVANCE: Failure to
      maintain pregnancy in aged, subfertile mares may be a result of a suboptimal
      oviductal environment exerting its effects on the conceptus during early
      cleavage.

PMID- 8874732
TI  - Pulmonary vascular pressures of strenuously exercising thoroughbreds after
      administration of phenylbutazone.
AB  - OBJECTIVE: To determine the effects of phenylbutazone administration on heart
      rate and right atrial and pulmonary vascular pressures in Thoroughbreds during
      rest and during exercise performed at maximal heart rate. ANIMALS: 7 healthy,
      exercise-conditioned Thoroughbreds. PROCEDURE: Horses were studied on 3
      occasions: without medication [control], after i.v. administration of
      phenylbutazone (4.4 mg/kg of body weight) at 12-hour intervals for 2 days and a
      final dose given 1 hour before exercise, and after i.v. administration of
      phenylbutazone for 2 days in the same manner, but with the final dose given 24
      hours before exercise. Horses were studied at rest and during exercise performed
      at maximal heart rate on a treadmill. Right atrial and pulmonary vascular
      pressures were measured with catheter-tip manometers referenced at the point of
      the shoulder. RESULTS: We did not detect significant differences in heart rate or
      right atrial and pulmonary vascular pressures among values recorded when horses
      were not given medication and values recorded when phenylbutazone was
      administered by either regimen. Exercise-induced pulmonary hemorrhage occurred in
      6 of the 7 horses regardless of whether phenylbutazone was administered or the
      dosage regimen used. CONCLUSIONS: In these Thoroughbreds, phenylbutazone
      treatment did not modify heart rate or right atrial and pulmonary vascular
      pressures at rest or during exercise capable of eliciting exercise-induced
      pulmonary hemorrhage. Thus, because phenylbutazone is a potent inhibitor of
      cyclooxygenase, prostaglandins probably do not play a role in mediating exercise
      induced pulmonary hypertension in horses. CLINICAL RELEVANCE: Phenylbutazone
      administration did not modify the pulmonary capillary hypertension in the
      strenuously exercising Thoroughbreds, and therefore, is unlikely to alter the
      prevalence or severity of exercise-induced pulmonary hemorrhage in Thoroughbred
      race-horses.

PMID- 8874733
TI  - Effects of ozone and airway inflammation on glutathione status and iron
      homeostasis in the lungs of horses.
AB  - OBJECTIVE: To investigate the effects of ozone and airway inflammation on indices
      of oxidant injury in horses. ANIMALS: 5 clinically normal horses and 25 horses
      referred for poor performance. PROCEDURE: Blood, tracheal wash, and
      bronchoalveolar lavage fluid samples were collected before and after ozone
      exposure (n = 5) or from clinical cases (n = 25), and were analyzed for reduced
      glutathione (GSH), glutathione disulfide (GSSG), and free and total iron (Fe)
      values. A scoring system (0 to 5) was used to assess airway inflammation on the
      basis of clinical signs and cytologic analysis of the tracheal wash and
      bronchoalveolar lavage fluid samples. RESULTS: Ozone induced significant (P <
      0.05) increases in GSH (195.4 +/- 68.5 microM), GSSG (19.4 +/- 6.4 microM), and
      free (25.5 +/- 16.1 microM) and total (93.1 +/- 13.4 microM) Fe values in the
      pulmonary epithelial lining fluid, compared with preozone samples (49.2 +/- 18.6,
      2.4 +/- 1.2, 0.0, and 33.1 +/- 5.9 microM, respectively). The presence of airway
      inflammation (19/25) was associated with high GSSG and free and total Fe, but not
      GSH, values in epithelial lining fluid, compared with values for clinically
      normal horses (6/25). There were no differences in the systemic values of GSH,
      GSSG, and free and total Fe between any of the groups. A strong correlation (r =
      0.84; P < 0.001) existed between inflammation score and the glutathione redox
      ratio (GSSG/[GSH + GSSG]) in the 25 horses admitted for clinical examination.
      CONCLUSIONS: Oxidant injury in the lung will induce changes in the glutathione
      status and Fe homeostasis that could affect pathogenesis of the disease. CLINICAL
      RELEVANCE: Measurement of indices of oxidant injury may be useful in the
      diagnosis of airway inflammation and the response to inhaled oxidants.

PMID- 8874734
TI  - Effects of pentoxifylline on hemorheologic alterations induced by incremental
      treadmill exercise in thoroughbreds.
AB  - OBJECTIVES: To determine whether pentoxifylline treatment altered hematologic,
      rheologic, electrolyte, or blood gas test results of Thoroughbreds during
      submaximal treadmill exercise. ANIMALS: 5 healthy Thoroughbreds that had raced
      within the past year and had no history of exercise-induced pulmonary hemorrhage.
      PROCEDURE: Mixed venous blood samples were obtained before exercise, at treadmill
      speeds of 9 and 13 m/s, and 20 minutes after exercise; hematologic, rheologic,
      electrolyte, and blood gas test results were determined. RESULTS: Pentoxifylline
      treatment resulted in a 45% reduction in RBC filtration pressures for horses at
      rest. The improved RBC filterability persisted during treadmill exercise. Horses
      treated with pentoxifylline had a greater decrease in Po2 values and a lesser
      increase in plasma lactate concentration during treadmill exercise. CONCLUSION:
      Administration of pentoxifylline improved RBC deformability of horses at rest and
      during treadmill exercise. CLINICAL RELEVANCE: Improved RBC deformability
      resulting from pentoxifylline treatment may reduce exercise-associated shear
      stress in pulmonary capillaries, thereby attenuating exercise-induced pulmonary
      hemorrhage.

PMID- 8874735
TI  - Identification of lactoferrin in bovine tears.
AB  - OBJECTIVE: To determine whether bovine tear film contains the iron-binding
      glycoprotein, lactoferrin. ANIMALS: 40 Adult Hereford, Angus, and Simmental
      cattle. PROCEDURE: Protein analysis: pooled bovine tears were used for protein
      analysis (size exclusion high-performance liquid chromatography [HPLC]
      fractionation). HPLC was used for tear analysis. A diode array detector was used
      (215 and 280 microns) for chromatogram analysis and comparisons. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE): protein electrophoresis
      was performed, using 7.5% running gels with 4% stacking gels. Molecular weight of
      proteins in the unknown samples was determined as recommended by the manufacturer
      of the standards. Protein sequencing: amino acid sequencing, using automated
      Edman degradation of HPLC purified protein, was performed. The sequence obtained
      was compared with the known protein sequence of bovine lactoferrin. RESULTS: HPLC
      analysis of whole bovine tears resulted in a consistent chromatogram. Peak
      collection was performed to recover a protein from the bovine tear film with
      chromatogram characteristics nearly identical to purified bovine lactoferrin.
      Silver-stained SDS-PAGE of this peak revealed a band with molecular mass
      consistent with bovine lactoferrin (estimated mass of 78 kd). The first 13 amino
      acid residues of this protein were identical to the amino acid sequence of bovine
      lactoferrin. CONCLUSION: Analysis of whole bovine tears, using size exclusion
      HPLC, SDS-PAGE, and amino acid sequencing, provided evidence that bovine tears
      contain lactoferrin. CLINICAL RELEVANCE: Lactoferrin probably exerts a
      bacteriostatic effect in bovine tear film. Locally produced lactoferrin may bathe
      the ocular surface and sequester iron from potential pathogens.

PMID- 8874736
TI  - Characteristics of fetal heart rate changes during the expulsive stage of bovine
      parturition in relation to fetal outcome.
AB  - OBJECTIVE: To characterize fetal heart rate (FHR) patterns of nonacidotic (N-AC)
      and acidotic (AC) calves during the expulsive stage of parturition. ANIMALS: 32
      calves born to heifers, either unassisted or by moderate traction. PROCEDURE:
      Cardiotocograms (CTG) evaluated qualitatively (visual) and quantitatively by a
      moving window technique (width 10, shift 5 minutes) for baseline FHR,
      variability, and periodic alterations (accelerations and decelerations). RESULTS:
      Significant differences were apparent between increase in baseline FHR of N-AC
      and AC calves; change in FHR (delta-FHR), taking into account individual FHR, is
      a more discriminating parameter. The predominant reaction to uterine contraction
      is a decrease in FHR; variable decelerations were the most common type in both
      groups, and late decelerations were seen only in AC calves. Additional
      characteristics of variable decelerations were more frequently seen in AC calves.
      CONCLUSIONS: CTG parameters during expulsion can discriminate between AC and N-AC
      calves, but specific characteristics are not exclusively restricted to AC or N-AC
      calves. CLINICAL RELEVANCE: CTG recordings during bovine parturition in cattle
      provide information on the fetal condition and can be used in the future to study
      the effects of medication and manipulations to the fetus.

PMID- 8874737
TI  - Postimplantation increase in plasma fibrinogen concentration with increase in
      relaxin concentration in pregnant dogs.
AB  - OBJECTIVE: To determine time courses of pregnancy-related changes in plasma
      fibrinogen, serum relaxin, and serum C-reactive protein-like immunoreactivity
      (CRP-LI) concentrations in pregnant and nonpregnant dogs. ANIMALS: 16 pregnant
      and 13 nonpregnant Beagles, 6 pregnant Beagles, and 3 pregnant and 3 nonpregnant
      dogs of other breeds. PROCEDURE: Fibrinogen was measured by nephelometric
      centrifugal analysis of light scatter in plasma samples of all dogs, and CRP-LI
      was measured by fluorescence immunoassay in selected sera from 10 pregnant and 10
      nonpregnant dogs. Relaxin was measured in selected sera from 7 pregnant and 7
      nonpregnant dogs. RESULTS: During pregnancy, fibrinogen concentration increased
      between days 21 and 30 after the luteinizing hormone surge, and was > 280 mg/dl
      between days 29 and 50 in 84 of 86 samples, with peak values 539 +/- 29 mg/ dl
      higher (P < 0.01) than those in nonpregnant dogs (188 +/- 8 mg/dl), higher values
      from days 21 to 50 (P < 0.01) than those in nonpregnant dogs, and values similar
      to those in nonpregnant dogs after day 50. Relaxin concentration was increased
      from days 26 to 30 and 0 to 4 days after fibrinogen concentration increased in
      pregnant dogs, and was not detectable in nonpregnant dogs. The CRP-LI
      concentration was higher in pregnant dogs at days 26 to 50, but values were
      inconsistent within and among dogs, and near the limit of sensitivity of the
      assay. CONCLUSIONS: Concentration of the acute-phase reactant protein fibrinogen
      increases after day 20 following implantation in dogs, at or just before the
      pregnancy-specific increase in relaxin concentration from days 26 to 30, and
      persists until day 50. CLINICAL RELEVANCE: Fibrinogen assay may be useful for
      pregnancy diagnosis in dogs.

PMID- 8874738
TI  - In vitro determination of equine third metacarpal bone unloading, using a full
      limb cast and a walking cast.
AB  - OBJECTIVE: To improve fracture treatment, in vitro experiments were performed to
      study the influence of a full limb cast and a walking cast on the loading regimen
      of bones in the distal portion of the equine forelimb. ANIMALS: 6 forelimbs of 6
      Shetland ponies. PROCEDURE: Loading of the third metacarpal bone was considered a
      representative measure for distal limb loading. Electrical resistance rosette
      strain gauges were attached to the dorsal, palmar, medial, and lateral surfaces
      of the midshaft of this bone in 6 forelimbs of 6 Shetland ponies. The limbs were
      tested in a pneumatic loading device to a maximal load of 1,500 N. RESULTS: Both
      casts decreased the amount of compressive forces acting on the metacarpal bone.
      Application of a full limb cast resulted in a variable and eccentric decrease,
      remaining strains ranging from 84 to 7% of the baseline value. A walking cast was
      superior in that it gave a centric and more uniform reduction of compressive
      loading to < 11% of the baseline value. Moreover, a walking cast neutralized the
      bending and torsion components of the loading. CONCLUSION: This study confirmed
      the clinical experience that a walking cast creates more reliable and favorable
      conditions for healing of fractures than does a full limb cast.

PMID- 8874739
TI  - Hematologic, hemostatic, and biochemical effects in dogs receiving an oral
      chondroprotective agent for thirty days.
AB  - OBJECTIVE: To evaluate the effect of a chondroprotective agent on hematologic,
      hemostatic, and biochemical variables in clinically normal dogs when administered
      over 30 days. ANIMALS: 13 clinically normal Beagles of either sex. PROCEDURE:
      Hematologic and hemostatic variables were assessed prior to treatment and on days
      3, 14, and 30 of treatment. Biochemical variables were assessed before treatment
      and on day 30 of treatment. RESULTS: Significant (P < 0.05) decreases were noted
      in hematocrit, hemoglobin, WBC, and segmented neutrophil variables on days 3 and
      14 of treatment. A significant decrease in red distribution width was noted on
      days 3 and 30, in RBC count on day 3, and in lymphocyte numbers on day 30. There
      were also significant reductions of aggregation in response to adenosine
      diphosphate and collagen on days 14 and 30. Significant decreases were noted in
      total ATP release in response to collagen on days 14 and 30, as well as
      significant decrease in platelet count on days 14 and 30. No changes were noted
      in prothrombin time, activated partial thromboplastin time, mucosal bleeding
      time, or biochemical variables during the study. CONCLUSIONS: Administration of
      this chondroprotective agent causes minor but not clinically important changes in
      hematologic and hemostatic variables in young, clinically normal dogs. CLINICAL
      RELEVANCE: Oral chondroprotective agents are widely prescribed in veterinary
      medicine for the treatment of degenerative joint disease; however, to date,
      little is known about safety of their use.

PMID- 8874740
TI  - Metabolic and histologic effects of recombinant canine somatotropin on bone
      healing in dogs, using an unstable ostectomy gap model.
AB  - OBJECTIVE: To investigate the effect of recombinant canine somatotropin (STH) on
      the metabolic and histologic aspects of bone healing in dogs, using an unstable
      ostectomy gap model. ANIMALS: 8 mature dogs. PROCEDURE: A 3-mm ostectomy of the
      mid portion of the radius was performed in all dogs. Implants designed to release
      STH at a rate of 4 mg/d were placed SC in 4 dogs (treated group [STHG]), and
      another 4 dogs received no implants (control group [CG]). Serum concentrations of
      STH, insulin-like growth factor I, and osteocalcin were determined before
      surgery, and weekly for 8 weeks. Scintigraphic evaluation of the ostectomy sites
      was performed before surgery, and at weeks 2, 4, 6, and 8 after surgery.
      Histologic evaluation ofthe ostectomy sites was performed at the conclusion of
      the study at week 8. RESULTS: Significant (P < 0.05) increases in serum STH,
      insulin-like growth factor I, and osteocalcin concentrations were observed in
      dogs of the STHG during the 8-week study period. Scintigraphic activity of the
      ostectomy sites was increased in dogs of both groups, but dogs of the STHG had
      significantly (P < 0.05) greater activity, compared with dogs of the CG.
      Coalescence of nuclear activity across the ostectomy site was observed in dogs of
      the STHG, whereas dogs of the CG maintained 2 distinct areas of metabolic
      activity. Histologically, dogs of the STHG had bridging calluses with areas of
      endochondral ossification and ongoing osteogenic activity, whereas dogs of the CG
      had nonossified fibrocartilage typical of nonunion fractures. CONCLUSION: Using
      the ostectomy gap model, recombinant canine STH enhanced the metabolic and
      histologic aspects of bone healing in dogs.

PMID- 8874742
TI  - Small, freshly arrived histiocytes in cutaneous and mucosal herpetic lesions.
AB  - We report on the predominance of a special type of small histiocyte in the
      inflammatory infiltrate accompanying herpetic bullae. These histiocytes, which
      have previously been taken to be neutrophils, are freshly arrived cells with a
      hitherto unknown function. Until now, they have been found only in Sweet's
      syndrome and erythema nodosum where they form Miesscher's radial granulomas.
      Similar small histiocytes were found in half of those herpetic lesions with
      intact bullae, and in over two-thirds of ulcerated lesions in which these cells
      formed a palisade in the fibrinoid material covering the floor of the ulcerated
      vesicles. Small histiocytes, admixed with neutrophils, were in close proximity to
      virally infected keratinocytes. Immunohistochemical analysis confirmed their
      histiocytic nature. With the exception of ecthyma contagiosum (orf), similar
      small histiocytes were not found in other viral infections or in nonspecific
      ulcers of the skin. In cases of herpetic folliculitis, small histiocytes showed
      massive epidermotropism towards hair follicle epithelium. We conclude that
      cutaneous and oral herpetic infections represent yet another disease in which
      small, freshly arrived histiocytes occur. They may be involved in antigen
      presentation, or in killing of infected keratinocytes.

PMID- 8874741
TI  - Reduced proliferative responses of peripheral blood mononuclear cells
      specifically to Candida albicans antigen in patients with atopic dermatitis-
      comparison with their normal reactivity to bacterial superantigens.
AB  - Although reduced cutaneous reactivities to Candida albicans have been reported in
      patients with atopic dermatitis (AD), there is still controversy as to whether
      the in vivo lymphocyte proliferation response is normal or reduced. We have also
      reported that patients with AD manifest a decreased cutaneous response only to C.
      albicans antigen in scarification patch tests. The purpose of this study was to
      examine whether patients with AD show normal lymphocyte transformation responses
      to C. albicans antigen. Peripheral blood leucocytes (PBL) from 21 patients with
      AD and 14 healthy control (HC) subjects were cocultured with optimal
      concentrations of C. albicans antigen and of superantigens (staphylococcal
      enterotoxin A and B). PBL from the patients with AD showed a significantly lower
      response to C. albicans antigen, but there was no statistically significant
      difference in PBL responses to superantigens between the patients with AD and the
      HC subjects. This decreased proliferative response of PBL was particularly
      noticeable in those whose RAST scores for C. albicans antigen were high. These
      results suggest the development of a specific anergy to C. albicans antigen in
      patients with AD.

PMID- 8874743
TI  - The majority of bullous pemphigoid and herpes gestationis serum samples react
      with the NC16a domain of the 180-kDa bullous pemphigoid antigen.
AB  - A series of previous studies have indicated that the NC16a domain of the 180-kDa
      bullous pemphigoid antigen (BP180) is the most immunogenic and probably
      pathogenic region in both bullous pemphigoid and herpes gestationis. To confirm
      these previous results by a large-scale study, we examined serum from 154 bullous
      pemphigoid and 43 herpes gestationis patients using an immunoblot technique with
      the BP180 NC16a domain fusion protein, which had been prepared using cDNA
      obtained from a human keratinocyte cDNA library by polymerase chain reaction
      amplification. This fusion protein was recognized by 90% of bullous pemphigoid
      and 79% of herpes gestationis serum samples, but not by any other disease or
      normal control serum samples. These results indicate that this system is very
      sensitive and specific for the detection of anti-BP180 antibodies and should be
      useful for the diagnosis of various subepidermal bullous diseases.

PMID- 8874744
TI  - The immunohistochemical effects of a single challenge with an intermediate dose
      of ultraviolet B on normal human skin.
AB  - Ultraviolet B (UVB) irradiation has extensively been advocated for use in the
      investigation of cutaneous inflammation in vivo. Mostly doses above the threshold
      of skin damage have been used. Therefore it is not clear whether the changes
      observed are specific effects of UVB or to a certain extent represent wound
      healing. In this study the dose-dependent effects of UVB on normal human skin
      were assessed using histology and immunohistochemistry. The dose of 1 MED was
      chosen as a dose unducing tissue changes with adequate morphology: no toxicity
      but evident immunohistochemical changes. The sequential effects of this 1 MED of
      UVB were studied for up to 14 days after irradiation, using immunohistochemistry
      with a panel of monoclonal antibodies. Substantial effects were observed, mainly
      on proliferation and differentiation; the markers for inflammation did not reveal
      major changes. This model might be a promising approach to evaluate the effect of
      drugs on epidermal proliferation and differentiation in vivo.

PMID- 8874745
TI  - Influence of topical photodynamic therapy with 5-aminolevulinic acid on porphyrin
      metabolism.
AB  - Photodynamic therapy (PDT) with topically applied 5-aminolaevulinic acid (5-ALA)
      is increasingly used for treating tumours. The efficacy of topical PDT is limited
      to superficial and initial tumours. The topically applied doses of 5-ALA vary
      from 0.02 to 7.0 g per session according to the type of lesion. There are no
      studies on the influence of topically applied 5-ALA on the systemic accumulation
      of porphyrins or porphyrin precursors. A group of 20 patients with actinic
      keratoses (AK) and basal cell carcinomas (BCC) were treated by topical PDT with 5
      ALA. Prior to and 6 and 24 h after PDT, 5-ALA and total porphyrin concentrations
      were determined in red blood cells and plasma, respectively. In addition, before
      and after 5-ALA treatment, 24-h urine samples were collected and porphyrins and
      porphyrin precursors were measured. There was no significant alteration in
      porphyrin metabolism. In some patients, a slight but insignificant increase in
      erythrocyte and plasma porphyrins was found 6 h after 5-ALA PDT. This
      investigation confirms clearly the safety of this treatment modality and
      demonstrates that 5-ALA application (up to 7 g) in the course of PDT has no
      influence on the concentrations of porphyrins and porphyrin precursors measured
      in various compartments.

PMID- 8874746
TI  - Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl
      5-methoxytryptamine). A dose response study.
AB  - Oxygen-centred free radicals play an important role in the pathogenesis of acute
      and chronic UV-induced skin damage as well as in skin aging. In this double-blind
      randomized study the efficacy of topically applied melatonin (N-acetyl-5
      methoxytryptamine), a potent free radical scavenger, in the suppression of UV
      induced erythema was assessed. A group of 20 healthy volunteers were irradiated
      with 0.099 J/cm2 UVB on four 5-cm2 areas on the lower back and topically treated
      with various concentrations of melatonin (0.05, 0.1, 0.5%) in a nanocolloid gel
      as carrier or with carrier alone. The UV-induced erythema was examined 8 and 24 h
      after irradiation by visual scoring and chromametry. A distinct dose response
      relationship was observed between the topical dose of melatonin and the degree of
      UV-induced erythema. Significant differences (P < 0.05) were found in redness
      (chromameter a-value and visual scoring) 8 h after irradiation between the areas
      treated with melatonin at 0.5% and those treated with melatonin at 0.05% or with
      the carrier. These results might open a new approach in the prevention and
      control of free radical-influenced skin diseases.

PMID- 8874747
TI  - Behaviour of laminin 1 and type IV collagen in uninvolved psoriatic skin.
      Immunohistochemical study using confocal laser scanning microscopy.
AB  - Previous studies have demonstrated the presence in psoriatic lesions of
      ultrastructural and molecular alterations of the basement membrane and an altered
      polarized distribution of the integrins; this latter alteration has also been
      observed in uninvolved skin. The aim of the present study was to determine, by
      means of immunolocalization with monoclonal antibodies directed against laminin 1
      and type IV collagen and using confocal scanning laser microscopy, whether there
      are also alterations of the main components of the basement membrane in
      uninvolved skin. The findings showed a discontinuous and fragmented staining of
      laminin 1 and a normal distribution of type IV collagen. Taking into account both
      these results and the results of studies on epithelial cell lines, the authors
      hypothesize the existence of a functional deficit in psoriatic keratinocytes
      affecting the synthesis of the alpha 1 subunit of laminin. This deficit would
      explain: (1) the incapacity to produce mature trimeric laminin; (2) the altered
      assembly into a distinct basal lamina; (3) the loss of keratinocyte adhesion to
      the basement membrane; (4) alterations in the polarized distribution of the
      integrins; and (5) the consequent total or partial block of the cell signals
      regulating the processes of cytomorphosis. Already present in uninvolved skin,
      and enhanced by various irritative stimuli, this situation could be decisive for
      the appearance of psoriatic lesions.

PMID- 8874748
TI  - Effects of Pityrosporum ovale on proliferation, immunoglobulin (IgA, G, M)
      synthesis and cytokine (IL-2, IL-10, IFN gamma) production of peripheral blood
      mononuclear cells from patients with seborrhoeic dermatitis.
AB  - The aetiology of seborrhoeic dermatitis (SD) is still unknown. An increased
      number of Pityrosposurm ovale in lesional skin of patients with SD has been
      suggested to play a crucial role in the pathogenesis of the disease since double
      blind trials with antifungal drugs (e.g. ketoconazole) have shown that these
      agents result in a significantly reduced disease intensity. The frequent
      association of HIV infection and SD may be due to a suppressed cell-mediated
      immunity. In order to characterize the role of the humoral and cellular immune
      response in patients with SD the effects of a P. ovale extract on the
      proliferation of, and interleukin-2 (IL-2), IL-10 by an interferon-gamma (IFN
      gamma) production, and immunoglobulin (IgA, IgG, IgM) synthesis by peripheral
      blood mononuclear cells (PBMC) from patients with SD were studied in vitro.
      Healthy volunteers served as controls. PBMC from normal donors responded with a
      significantly increased proliferation to P. ovale antigen, whereas cells from
      patients with SD did not. Additionally, IL-2 and IFN gamma production by PBMC
      from patients with SD was markedly depressed compared with normal cells after
      stimulation with P. ovale. However, stimulation of PBMC from SD patients with P.
      ovale antigen induced significantly increased IL-10 synthesis. IgA, IgG and IgM
      synthesis was significantly increased in cultures of PBMC from patients with SD
      whether the cells were antigen-stimulated or not. Our results support the
      assumption that strong skin colonization with P. ovale in SD is due to an altered
      cellular immunity, which may be induced by increased IL-10 secretion.

PMID- 8874749
TI  - Topical tretinoin increases dermal mast cells, induces epidermal mast cell growth
      factor (c-kit ligand) and modulates its distribution in hairless mice.
AB  - In previous studies we have noted that mast cells are increased in tretinoin
      treated photoaged hairless mouse skin. Because UV radiation is known to increase
      mast cell numbers, we were interested in whether tretinoin alone would modulate
      the mast cell population in unirradiated mice. Animals were treated topically
      with 0.05% tretinoin, 5 days a week, for 2, 4, 6, 8 and 10 weeks. Untreated and
      vehicle controls were included. Biopsies were processed for light microscopy and
      stained with toluidine blue. Mast cells in the upper and lower dermis were scored
      separately under high magnification. After 2 weeks of tretinoin, mast cells in
      the upper dermis were significantly increased, as indicated by the appearance of
      small, moderately metachromatically granulated cells near the dermal-epidermal
      junction. Mast cells in the lower dermis, the site of a granulomatous reaction,
      were large, densely granular and significantly increased after 6 weeks of
      treatment. Immunohistochemical evaluation for mast cell growth factor (MGF)
      revealed a marked increase in keratinocyte cytoplasmic staining by week 2. After
      4-6 weeks, membrane-associated or intercellular staining was evident. Cells in
      the upper dermis also showed membrane reactivity for MGF. By 8-10 weeks,
      epidermal MGF reactivity had dissipated in the more basal keratinocytes. These
      findings show that topical tretinoin can induce epidermal MGF along with an
      associated mast cell hyperplasia. It is suggested that the two populations of
      dermal mast cells may have different functions.

PMID- 8874750
TI  - Incidence and in-vivo relevance of anti-interferon antibodies during treatment of
      low-grade cutaneous T-cell lymphomas with interferon alpha-2a combined with
      acitretin or PUVA.
AB  - Interferon-alpha combined with retinoid or PUVA is used for the treatment of
      cutaneous T-cell lymphoma. Anti-IFN-alpha antibodies (IFN ab) occur regularly
      during IFN-alpha treatment. We investigated the incidence of neutralizing and
      binding IFN ab and analysed their relationship with clinical and immunological
      parameters. A group of 17 CTCL patients were treated with IFN alpha-2a three
      times weekly subcutaneously at a dose of 3 Mill. I.U. combined either with
      retinoid (acitretin, Neotigason; 0.5 mg/kg bodyweight) daily or with 5
      methoxypsoralen (1.2 mg/kg bodyweight) plus UVA radiation three times weekly.
      Prior to and during treatment we monitored stage, skin involvement by a tumour
      burden index, serum levels of beta 2-microglobulin, neopterin, binding and
      neutralizing IFN ab, Interleukin-6 (IL-6), soluble IL-2 receptors (sIL-2r) and
      the CD4/CD8 ratio of peripheral blood mononuclear cells. We observed two
      complete, two partial and six minor responses, four patients with stable disease
      and three patients with progressive disease. Of the 17 patients, 7 developed
      binding IFN ab, but only 2 had neutralizing IFN ab which were associated with
      high titres of binding IFN ab. IFN ab formation was more frequent in patients
      with normal CD4/CD8 ratios and a high tumour burden index and showed a trend to
      be more frequent in PUVA-cotreated patients than in retinoid-cotreated patients.
      Responses were more frequently seen in IFN ab-negative patients. IFN ab developed
      in patients treated with PUVA or retinoid combined with IFN. Binding as well as
      neutralizing IFN ab may have an impact on the treatment success in CTCL patients.

PMID- 8874751
TI  - Autoradiographic mapping of beta-adrenoceptors in human skin.
AB  - A high density of beta 2-adrenoceptors has been found in human skin. Using
      autoradiographic mapping we investigated the distribution of beta 1- and beta 2
      receptors in normal and diseased human skin. Cryostat sections of human skin
      obtained at biopsy were incubated with [125I]-iodocyanopindolol and nonspecific
      binding was identified by incubation of adjacent sections with 200 microM (-)
      isoproterenol; beta 2-receptors were visualized using CGP 20712A and beta 1
      receptors using ICI 118,551 as competing agents. The epidermis was densely
      labelled with an even distribution throughout all layers. Most of the beta
      receptors were of the beta 2-subtype, with practically no beta 1-receptors. beta
      Receptors were also localized to eccrine sweat glands, dermal blood vessels, and
      perivascular inflammatory cells, but there was no labelling of sebaceous glands.
      Topical glucocorticoids caused an increase in the density of epidermal beta
      receptors. We conclude that keratinocytes and eccrine sweat glands express high
      densities of beta 2-receptors, suggesting that they may have a physiological role
      in the regulation of these cells.

PMID- 8874752
TI  - Interleukin-1 beta upregulates tissue-type plasminogen activator in a
      keratinocyte cell line (HaCaT).
AB  - Human keratinocytes synthesize and secrete tissue-type plasminogen activator
      (tPA). tPA converts the inactive precursor enzyme plasminogen into the trypsin
      like proteinase plasmin. tPA is not found in normal epidermis, but in lesional
      epidermis from patients with a variety of cutaneous diseases, including
      psoriasis, pemphigus and pemphigoid. The presence of tPA is probably a reaction
      to the disease process rather than the initiating event in these etiologically
      and histopathologically diverse lesions. However, the factor(s) that upregulate
      tPA expression and secretion in keratinocytes have remained largely elusive. We
      sought to determine whether the inflammatory cytokine interleukin-1 beta (IL-1
      beta), which is commonly present in diverse epidermal lesions, influences tPA
      production. Accordingly, we studied the influence of IL-1 beta on secretion of
      tPA by cells of the human keratinocyte cell line HaCaT. We found that IL-1 beta
      increased tPA secretion in these cells. Given the observation that IL-1 beta is a
      common proinflammatory mediator in cutaneous diseases, our findings may explain
      the increase in tPA in clinically and etiologically diverse inflammatory
      epidermal lesions.

PMID- 8874753
TI  - Phenotypic alterations of neuropeptide Y, vasoactive intestinal peptide and
      choline acetyltransferase in rat cultured chromaffin cells as effected by nerve
      growth factor and glucocorticoid.
AB  - We assessed changes in neuropeptide Y (NPY), vasoactive intestinal peptide (VIP)
      and choline acetyltransferase (ChAT) immunoreactivities when neonatal rat
      chromaffin cells were cultured in a medium containing nerve growth factor (NGF),
      or the synthetic glucocorticoid dexamethasone (DEX), examining whether their
      expression was correlated with the morphological changes induced by NGF and DEX.
      All of the chromaffin cells in culture were tyrosine hydroxylase (TH)
      immunopositive regardless of whether they extended processes. TH-immunoreactive
      materials of NGF-treated chromaffin cells were distributed in all the cytoplasmic
      processes, even at the tips of growth cones. The percentage of NPY-positive
      chromaffin cells did not change markedly when treated with NGF or DEX throughout
      the 14 days in culture. The proportion of VIP-positive chromaffin cells increased
      gradually in the NGF-treated group and that of ChAT-positive cells in the group
      was similar to VIP. The morphological alterations induced by NGF were not
      correlated with the changes in proportions of NPY-, VIP- or ChAT-positive
      chromaffin cells. The percentages of VIP- or ChAT-immunopositive chromaffin cells
      in the NGF-treated group showed much greater increases than those in the DEX
      treated group. These findings suggest that NGF might modulate the phenotypic
      changes of neuropeptides and amines in rat chromaffin cells.

PMID- 8874754
TI  - Neurons with perineuronal sulfated proteoglycans in the mouse brain and spinal
      cord: their distribution and reactions to lectin Vicia villosa agglutinin and
      Golgi's silver nitrate.
AB  - This study demonstrates that many neurons in the somatosensory cortex, cingulate
      cortex, retrosplenial cortex and hippocampal subiculum of the mouse brain are
      covered by sulfated proteoglycans which are intensely negative-charged and
      stained with cationic iron colloid, while being digested with hyaluronidase.
      Neurons with similar perineuronal proteoglycans are also recognized in the
      extrapyramidal system (superior colliculus, red nucleus, reticular formation,
      vestibular nuclei and cerebellar nuclei), in the secondary auditory system
      (cochlear nuclei, nucleus of trapezoid body, inferior colliculus and nucleus of
      lateral lemniscus), in the vestibulo-ocular reflex system (vestibular nuclei and
      extraocular motor nuclei), and in the pupillary reflex system. The neurons with
      perineuronal sulfated proteoglycans in the cerebral cortices and hippocampal
      subiculum are usually labeled with the lectin Vicia villosa agglutinin, though
      those in the cerebellar, vestibular and cochlear nuclei may not be reactive to
      this lectin. Double staining of the retrosplenial cortex, hippocampal subiculum
      and cerebellar nuclei with Golgi's silver nitrate and cationic iron colloid
      indicates that the perineuronal sulfated proteoglycans are identical with the
      Golgi's reticular coating or glial nets.

PMID- 8874755
TI  - Perineuronal sulfated proteoglycans in the human brain are identical to Golgi's
      reticular coating.
AB  - Many neurons in the human somatosensory cortex (Area 7 of Brodmann) possess an
      intensely negative-charged surface coat consisting of perineuronal sulfated
      proteoglycans which were stained with cationic iron colloid. This surface coat
      was stained doubly with cationic iron colloid and Golgi's silver nitrate. The
      result indicates that the perineuronal sulfated proteoglycans are identical with
      Golgi's reticular coating, whose existence and nature have previously been
      controversial. The result also suggests that Golgi's silver nitrate stains the
      core proteins of proteoglycans.

PMID- 8874756
TI  - Studies of the choroid plexus and its associated epiplexus cells in the lateral
      ventricles of rats following an exposure to a single non-penetrative blast.
AB  - The choroid plexus in rats exhibited ultrastructural changes following a non
      penetrative blast. The immunophenotypic features of epiplexus cells associated
      with the choroid plexus epithelium were also altered. In rats killed at 1 and 7
      days after the blast, the intercellular spaces between the epithelial cells were
      greatly widened, coupled with the massive eruption and possible extrusion of the
      apical cytoplasm into the ventricular lumen. Associated with these changes was
      the passage of some monocytes/lymphocytes across the epithelium. The incidence of
      such a migratory phenomenon was more frequent in rats killed 7 days after the
      blast. In rats killed 14 days after the blast, the ultrastructural changes of the
      epithelial cells became less pronounced. At 21 and 28 days after the blast, the
      ultrastructure of the choroid plexus was comparable to that of normal specimens.
      The immunoreactivity of epiplexus cells in terms of their cell number and
      staining intensity with the monoclonal antibodies OX-42, OX-18, OX-6 and ED1 was
      noticeably augmented at 7 and 14 days after the blast; this, however subsided at
      21 and 28 days. It is concluded that the choroid plexus is extremely sensitive to
      a blast wave as manifested by its structural alterations and the vigorous
      expression of CR3 receptors and MHC antigens by the epiplexus cells. It is
      suggested that a possible immune response might have been triggered in the
      cerebrospinal fluid ventricular system following the blast.

PMID- 8874757
TI  - Lysosomal cysteine and aspartic proteinases and ubiquitin in rat and human
      urinary bladder epithelium.
AB  - To examine localization of cysteine and aspartic proteinases, and ubiquitin in
      rat and human urinary bladders, immunocytochemistry was applied to the tissues.
      In semi-thin sections, immunoreactivity for cathepsins B and D was densely
      localized throughout epithelial layers of rats and humans, while that for
      cathepsins H and L was mainly localized in rat superficial and human intermediate
      cells. Immunoreactivity for cathepsin C was relatively high in rat and human
      epithelia, especially in humans. Immunoreactivity for ubiquitin was detected in
      rat and human epithelial cells. By electron microscopy, vesicular or
      heterogeneously dense lysosomes labeled with immunogold particles indicating
      cathepsin B were seen in rat and human epithelial cells; particularly, they often
      appeared near fusiform vesicles in rat superficial cells and in human
      intermediate and superficial cells. By double immunostaining, lysosomes with or
      without vesicular structures were co-labeled with immunogold particles showing
      both cathepsin B and ubiquitin. The results suggest that cathepsins B, C, H, and
      L, and cathepsin D are involved in the lysosomal system of rat and human bladder
      epithelia. Moreover, considering that ubiquitin is a cofactor in the soluble ATP
      dependent proteolysis, the results may also indicate that epithelial cells
      actively form autophagolysosomes.

PMID- 8874759
TI  - Distribution of lymphatics in human palatine tonsils: a study by enzyme
      histochemistry and scanning electron microscopy of lymphatic corrosion casts.
AB  - The distribution of lymphatics in human palatine tonsils was studied by enzyme
      histochemistry for 5'-nucleotidase (5'-Nase) and scanning electron microscopy
      (SEM) of lymphatic corrosion casts. The palatine tonsils were found to possess
      lymphatics in the parafollicular area (i.e., interfollicular, interfolliculo
      septal, and folliculo-septal area), in the connective tissue septa, and in the
      capsules, but not in the subepithelial area between the follicles and the
      follicle-associated epithelia or within the follicles. The tubular lymphatics
      originated some 200-300 microns below the epithelium and formed a three
      dimensional network in the parafollicular area. Some lymphatics around the lower
      part of the follicle were flat, wide, and irregular in shape, and thus appeared
      to be lymphatic sinuses, referred to as perifollicular lymphatic sinuses. The
      lymphatics in the parafollicular area drained into the septal lymphatics, which
      ran rather straight in the connective tissue septa. The septal lymphatics finally
      gathered into the broader capsular lymphatics. Most of the septal and capsular
      lymphatics were endowed with valves. Our results indicate that lymphocytes and
      fluid from the follicles and the subepithelial region enter the perifollicular
      lymphatic sinuses and/or the interfollicular lymphatics, pass through the
      interfolliculo- and folliculo-septal lymphatics, and finally enter the septal and
      capsular lymphatics to leave the tonsil.

PMID- 8874758
TI  - Immunocytochemical localization of prohormone convertases PC1/PC3 and PC2 in rat
      pancreatic islets.
AB  - The prohormone convertases PC1/PC3 and PC2 are endoproteases involved in
      prohormone cleavage at pairs of basic amino acids. To determine the cellular and
      subcellular distribution of PC1/PC3 and PC2 in the rat pancreas, we generated
      their polyclonal antisera in rabbits, using as immunogens two synthetic peptide
      antigens corresponding to amino acids 442-459 (ST-28) of PC1/PC3 and 613-629 (ST
      29) of PC2 and two bacterially expressed antigens covering amino acids 145-414
      (KN-1) of PC1/PC3 and 385-637 (KN-2) of PC2. Western blot analysis revealed the
      presence of PC1/PC3 (87 and 68 kDa) and PC2 (75 and 70 kDa) in rat pancreatic
      islets, indicating that the antisera are specific for the corresponding antigens.
      Immunocytochemical staining of serial sections demonstrated that the antibody
      against PC1/PC3 immunostained only insulin-producing cells, whereas the PC2
      antibody stained insulin, glucagon-, somatostatin-, and pancreatic polypeptide
      producing cells. Double-immunolabeling of the prohormone convertases and
      pancreatic hormones with gold particles of different sizes revealed that insulin
      positive secretory granules were also immunolabeled with PC1/PC3 and PC2
      antibodies, whereas glucagon-, somatostatin-, or pancreatic polypeptide-positive
      granules were labeled only with the PC2 antibody. This differential localization
      of PC1/PC3 and PC2 provides a further problem on the substrate-specificity of
      these enzymes in the processing of pancreatic prohormones.

PMID- 8874760
TI  - Age-related changes in Meissner corpuscles in the mouse palate: a histochemical
      and ultrastructural study.
AB  - Meissner corpuscles in the palatine mucosae of ddY-mice of various ages were
      studied histochemically and electron microscopically. As the age of the animals
      advanced, regressive Meissner corpuscles with lessened or depleted activity of
      non-specific cholinesterase (ChE) increased in number. Immunohistochemistry for
      Na+/K(+)-ATPase showed that the complex ramification of axon terminals in
      Meissner corpuscles attained at maturation gradually changed to a sparse
      distribution as the animals aged. Only a few putative rudiments of Meissner
      corpuscles, which were completely devoid of nerve terminals, were encountered.
      Electron microscopy showed that the regressive Meissner corpuscles contained
      atrophic axons and lamellae in a disordered arrangement, although the severity of
      the atrophy differed depending on the degree of the regression. Furthermore, the
      Meissner corpuscles were found to progressively accumulate fibrous long-spacing
      fibers having a periodicity of 160 nm and unique spherical corpuscles 150-300 nm
      in diameter in their intercellular spaces. From these results we concluded that:
      1) the atrophy of the axon and lamellae proceeds almost simultaneously during the
      age-related regression of Meissner corpuscles; and 2) not only the atrophy of the
      axon and the lamellar cell but microenvironmental changes such as the
      accumulation of intercellular substances is also involved in the regression of
      these corpuscles.

PMID- 8874761
TI  - Different localizations of growth-associated protein (GAP-43) in mechanoreceptors
      and free nerve endings of adult rat periodontal ligament, dental pulp and skin.
AB  - Distributions of growth-associated protein-43 (GAP-43) in the periodontal
      ligament and dental pulp of adult rats were studied by light and electron
      microscopy. The mature periodontal ligament and dental pulp contained numerous
      GAP-43-positive neural elements, comprising periodontal Ruffini endings and thin
      nerve fibers, but expression patterns differed among the kinds of nerves. In the
      periodontal ligament of rat molars, immunoelectron microscopy revealed that GAP
      43 like immunoreactivity in the Ruffini ending, an essential mechanoreceptor, was
      confined to the Schwann sheaths around the axon terminals and was not in the axon
      terminals themselves, unlike free endings that revealed axonal GAP-43. However,
      the lamellar Schwann cells associated with the cutaneous receptors did not
      exhibit any GAP-43 like immunoreactivity though they were intensely reactive for
      low affinity nerve growth factor receptor (p75-NGFR), a marker for lamellar
      Schwann cells in mechanoreceptors. The characteristically uniform expression of
      GAP-43 in the Schwann lamellae that surround the Ruffini mechanoreceptors of rat
      molar ligament suggests that Schwann cells are involved in the GAP-43 mediated
      plasticity of these receptors. On the other hand, the pulpal nerves were filled
      with the reaction products in their axonal spaces, suggesting the potential for
      neuronal plasticity during normal function and after tooth injury.

PMID- 8874762
TI  - Professor Stefan Slopek (1914-1995).

PMID- 8874763
TI  - Cytokines in the treatment of hematological disorders: recent progress and
      perspectives.
AB  - Cytokines are involved in hematopoiesis by regulating proliferation,
      differentiation and cellular functions of various lineages of hematopoietic
      cells. There is an increasing range of clinical conditions in which cytokines are
      involved as therapeutic agents. One of the most advanced and successful
      applications is the stimulation of hematopoiesis by the colony stimulating
      factors (GM-CSF and G-CSF) and erythropoietin. Hematopoietic growth factors are
      effective in accelerating recovery from neutropenia after chemotherapy and bone
      marrow transplantation and in reducing incidence of infections. Interferon alpha
      (IFN-alpha) proved a useful therapeutic agent for chronic myelogenous and hairy
      cell leukemias as well as for multiple myeloma and non-Hodgkin's lymphoma.
      Interleukin 2 is the only cytokine apart from IFN-alpha accepted as
      antineoplastic agent. It may be useful as adjuvant therapy in the hematological
      malignancies. It may be supposed that in the near future new recombinant
      cytokines will be introduced in the treatment of blood diseases.

PMID- 8874764
TI  - Natural human interferon alpha may act differently when given parenterally or
      orally to patients chronically infected with hepatitis B virus.
AB  - A literature review of patients chronically infected with hepatitis B virus (HBV)
      treated with natural human interferon alpha (nHuIFN-alpha) given parenterally
      every day for 28 days revelated that even the daily dose of (5 x 10(6)IU) of IFN
      alpha inhibits cellular metabolism. As a result of metabolic block, the number of
      blood elements were diminished. Furthermore treated patients recorded several
      different adverse reactions. In contrast, among patients treated with the oral
      form of nHuIFN-alpha non metabolic block occurred and no adverse reactions were
      seen, even though the therapy lasted much longer. Two years after initiation of
      parenteral IFN-alpha therapy, the loss of HBV-BeAg was 53.8% and 28.8% of the
      patients had undergone seroconversion. In contrast, 77% of patients on oral
      interferon lost HBV-BeAg and 74% serconverted and normalized their biochemical
      liver function. The results suggest that the nHuIFN-alpha given orally and
      parenterally activate two different mechanisms responsible for virus elimination.

PMID- 8874765
TI  - Effect of a proline-rich polypeptide on IgG level in Chickens.
AB  - We have previously shown that a proline-rich polypeptide (PRP) from ovine
      colostrum expresses an immunoregulatory activity in mice on humoral and cellular
      immune response. The results presented in this communication show that PRP also
      modulates the immune response in chickens. PRP administered to the chickens in
      portions before, simultaneously or after the antigen, stimulated the antibody
      production. The enhancement of the immune response was also observed when a
      single dose was injected to the chicken before or simultaneously with the
      antigen. On the other hand, the single doses of PRP applied to the chickens after
      the immunization caused an inhibition of the production of antibodies.

PMID- 8874766
TI  - Interaction of human erythrocyte glycophorin with immunoglobulins G.
AB  - We have found that human glycophorin and asialoglycophorin interacted with human
      non-immune IgG. To characterize quantitatively the interaction between
      glycophorin and IgG we elaborated a direct solid-phase radioimmunoassay. We
      showed that the binding of IgG was reversible and saturable within the range of
      IgG concentrations used. Glycophorin bound higher amounts of aggregated than non
      aggregated immunoglobulins. The apparent association constant for non-aggregated
      human IgG was 5.45 +/- 0.93 x 10(5) M-1 and 1.13 +/- 0.78 x 10(6) IgG molecules
      were bound per 1 picogram of the glycophorin. The binding of glycophorin occurs
      within the F(ab)2 fragment of IgG, mainly.

PMID- 8874767
TI  - Antigenicity of human and horse myoglobins.
AB  - Rabbit antisera against human myoglobin and horse myoglobin cross-reacted with
      both myoglobins but only one of them recognized human hemoglobin. Two mouse
      monoclonal antibodies anti-human myoglobin were obtained, but only one of them
      (No. 49) cross-reacted with horse myoglobin. Antibody No. 49 and rabbit
      antibodies reacted also with apo-, FITC- and treated with hydrochloric acid or
      TPCK-trypsin horse myoglobin, but their binding to myoglobin pretreated with NaOH
      was reduced. Thirteen peptides overlapping sequence of human myoglobin were
      synthesized on polyethylene pins. Rabbit and mouse polyclonal antibodies reacted
      with some of these peptides but no reaction was noted with mouse monoclonal
      antibodies. Two monoclonal antibodies were applied for specific immunoassay of
      human myoglobin.

PMID- 8874768
TI  - Inhibition of mouse liver cytochrome P-450 by gram-negative bacteria
      lipopolysaccharides.
AB  - The ability of bacterial endotoxins, of different origin, to modify the level of
      mouse liver cytochrome P-450 was investigated. Endotoxins, (lipopolysaccharides,
      LPSs) were isolated from Proteus, Escherichia, Salmonella, Bacteroides and
      Coxiella strains. The most potent inhibitor of cytochrome P-450 activity was S.
      typhi 0101 LPS, which at a dose of 1 microgram/mouse reduced the cytochrome P-450
      activity to 59%. E. coli O55:B5, S. typhimurium, P. mirabilis O3, and C. burnetii
      LPSs, at dose 10 micrograms/mouse, decrease cytochrome P-450 level from 56 to
      69%. B. ovatus LPS significantly suppressed the expression of cytochrome P-450
      only at the highest dose used-100 micrograms/mouse. The comparison of inhibitory
      activity of P. mirabilis complete, S and R types of LPSs indicate that lipid A
      portion of LPSs are sufficient to decrease the cytochrome P-450 level. However,
      the core oligosaccharide of LPS significantly enhance that inhibition. The
      isolated O-specific polysaccharide part of P. mirabilis O3 LPS did not decrease
      cytochrome P-450 level. The comparison of biological activity of Proteus LPSs,
      tested by chromogenic Limulus amebocyte lysate (LAL) test, demonstrated the
      enhancement effect of O-polysaccharide part of tested LPSs.

PMID- 8874769
TI  - Haptoglobin concentration in serum and other body fluids measured by comparison
      of its reactivity with hemoglobin and concanavalin A.
AB  - Haptoglobin (Hp) concentration in normal human sera was determined either by
      means of the reaction with hemoglobin (Hb) or by reaction with the lectin
      concanavalin A (Con A). The ratio of Hp-Con A (1.02 +/- 0.68 g/l) to Hp-Hb (1.10
      +/- 0.58 g/l) equal 0.96 +/- 0.32 was found to be characteristic for sera from
      healthy subjects. Measurements were also carried out for some pathological body
      fluids. Values of the ratio Hp-Con A/Hp-Hb in ascitic fluid, pleural effusion and
      cerebrospinal fluid were 1.72 +/- 1.13, 0.42 +/- 0.23 and 0.15 +/- 0.18.
      respectively. Haptoglobin present in urine and saliva was not recognized by Con
      A, whereas could form a complex with hemoglobin. Hp concentration determined by
      this method reached 2 mg/l.

PMID- 8874771
TI  - Effect of exogenous tumor necrosis factor alpha, interleukin 6 and interferons on
      vesicular stomatitis virus replication in human placenta and amniotic membrane
      organ cultures.
AB  - Effects of exogenous cytokines on replication of vesicular stomatitis virus (VSV)
      in amniotic membrane and placental organ cultures (OC) were studied. We compared
      the effects observed in OC and established human carcinoma cell lines: A549 and
      HEp-2. Recombinant human tumor necrosis factor alpha (rHuTNF-alpha), added to
      amniotic membrane, villous, or decidual OC at concentrations of 30 to 3000 U/ml,
      potentiated VSV replication by 10-1000 fold. Addition of 5 to 10000 U/ml of
      recombinant human interleukin 6 (rHuIL-6) to OC from 5 placentas was without
      effect on VSV growth, except one culture in which enhanced VSV replication has
      been observed. rHuTNF-alpha was found to have no effect on VSV growth in HEp-2
      and A549 cell cultures. In contrast, the placental OC were sensitive to antiviral
      activity of natural interferons (IFNs): alpha, beta and recombinant IFN-gamma,
      although A549 cells were 5 to 10 fold more responsive to the cytokines.

PMID- 8874770
TI  - Lactoferrin inhibits proliferative response and cytokine production of TH1 but
      not TH2 cell lines.
AB  - Bovine (BLF) and human (HLF) lactoferrin inhibit proliferation and cytokine
      production by an antigen specific TH1 cell line stimulated with antigen
      presenting cells (APC) and antigen. Beside the inhibitory effects on TH1 cells we
      observed a decrease of interleukin 2 receptor (IL-2R) expression on these cells
      contacted with LF. Lactoferrin (LF) did not inhibit proliferation of indicator HT
      2 cells to IL-2 suggesting lack of interference with IL-2/IL-2R interaction by
      LF. No inhibitory effect was observed on proliferation and cytokine production by
      TH2 cell lines and no changes in interleukin 4 receptor (IL-4R) levels were found
      with regard to TH2 cell line. We conclude that LF has differential activity with
      regard to effector functions of antigen-specific T cells by inhibiting TH1 but
      not TH2-mediated immune responses.

PMID- 8874772
TI  - Serological confirmation of human herpesvirus type 6 infection in different age
      groups.
AB  - Human herpesvirus type 6 (HHV-6) infection was proved by IgG immunofluorescence
      method. 354 sera at various age groups were tested and 161 sera from children in
      more detail. There was no significant differences in our results and obtained by
      other authors, when testing sera from adults. Our investigation of younger
      children sera confirmed that mother antibodies are transferred, but also suggest
      the possibility of virus vertical infection. Our study also confirmed that
      antibodies are acquired very early in life in the same age group as exanthema
      subitum does.

PMID- 8874773
TI  - Seleno-organic compounds as immunostimulants: an approach to the structure
      activity relationship.
AB  - Our studies on the seleno-organic compounds were focused at their activities as
      the modest cytokine inducers in human peripheral blood leukocyte cultures. Our
      bioassays used in the screening methods were based on the quantitative
      determinations of mainly two types of cytokines: interferons (IFNs) and tumor
      necrosis factors (TNFs). More recently we have found that several of the
      compounds have direct immunotropic actions in vitro and in vivo, in mice and in
      chickens. The paper summarizes the data related to the cytokine-inducing activity
      of 65 seleno-organic compounds divided into 4 groups according to their chemical
      structures. The reference compound was ebselen, the well known experimental drug
      with various biological activities. Approximately 50% of the compounds were found
      to be active in our bioassays. The selected compounds induced also IL-6 and GM
      CSF. Their activities were clearly correlated with defined chemical structures as
      well as with the presence of selenium. We suggest that some of the selected by us
      compounds, other than ebselen, are interesting as immunostimulants and potential
      antiviral agents and cytokine inducers active in humans.

PMID- 8874774
TI  - Spontaneous motility and chemotaxis of neutrophils is influenced by
      glycocorticosteroid therapy.
AB  - The migration of neutrophils is an important part of the allergic inflammatory
      response. The aim of our study was to investigate the effect of
      glucocorticosteroids (GCS) on the stimulated and unstimulated migration of
      neutrophils. The study comprised 103 asthmatics including 44 subjects under GCS
      therapy (20 GCS resistant and 24 GCS sensitive) as well as 96 healthy control
      individuals. Unstimulated (random) motility as well as chemotactic response
      towards fMLP (10-8 mol/l) were determined after Boyden method. Neutrophil
      motility was determined by the distance of the leading front in filter. In both
      resistant and sensitive asthmatics under GCS therapy we observed significantly
      increased unstimulated motility as compared to normal controls (p < 0.001).
      However, this effect was not demonstrated in the GCS untreated group. Neutrophil
      chemotaxis towards fMLP was increased in GCS untreated group as compared to
      healthy controls (p < 0.05). In GCS sensitive subjects the chemotatic activity
      was decreased. In GCS resistant asthmatics it was moderately increased. We
      conclude that increased unstimulated neutrophil motility might be one of the
      immunosuppressive mechanisms of GCS by preventing the cell accumulation at the
      sites of inflammation.

PMID- 8874775
TI  - ACTH and growth hormone in myocardial LDH adaptation to hypoxia in rats.
AB  - The role of hypophysis in cardiac growth, and in myocardial lactic dehydrogenase
      (LDH) isoenzyme adaptations to hypobaric hypoxia (9.5% O2) during 3 weeks was
      studied in four groups of hypophysectomized rats: one group received no hormone,
      and the second, third, and fourth groups received, respectively, growth hormone,
      ACTH, and growth hormone+ACTH. One hypophysectomized and one non-surgical group
      maintained at sea-level and one non-surgical group exposed to hypoxia served as
      controls. Exposure of hypophysectomized rats to hypoxia produced a proportional
      loss of body and heart weight with an equal decrease in both LDH subunits, H
      (heart) and M (muscle). Growth hormone and/or ACTH did not reverse cardiac
      atrophy. ACTH given alone or with growth hormone enhanced M-subunit synthesis (2-
      to 4-fold) and corrected the H/M ratio to the level of the non-surgical controls
      exposed to hypoxia, but at the expense of a lower total level of LDH. The
      adaptative changes in LDH isoenzymes induced by hypoxia could be abolished with
      hypophysectomy, and partly restored by giving growth hormone and ACTH, but this
      restoration was not coupled with cardiac growth.

PMID- 8874776
TI  - Early proliferative changes in hearts of hypertensive Goldblatt rats: an
      immunohistochemical and flow-cytometrical study.
AB  - Hyperplasia of myocytes in cardiac adaptation is a rare event in the mammalian
      cardiac muscle. Recent findings support the concept that proliferation of
      myocytes in the adult mammalian heart may be induced after a prolonged increase
      in pressure load on the myocardium. To determine whether short-term hypertension
      leads to hyperplasia of myocyte nuclei in the rat heart renal hypertension was
      produced in 12 Wistar rats. As soon as hypertension occurred, bromodeoxyuridine
      (BrdU) (50 mg/kg/day) was injected intraperitoneally on three subsequent days.
      Twelve sham-operated rats served as controls. After 3 days, the left cardiac
      ventricle was excised and double-staining with anti-BrdU antibody and propidium
      iodide was performed to determine the phase of cell-cycle of the BrdU-positive
      cells by flow-cytometry. Immunohistochemical double-staining with desmin, smooth
      muscle actin, vimentin, and BrdU was done to classify the BrdU-positive cells.
      Most of the BrdU-positive cells were in the G0/G1-phase of the cell-cycle,
      suggesting cell proliferation or DNA-repair have taken place; polyploidy was not
      observed. In the hypertensive group (4.62% +/- 2.36) significantly more cells
      incorporated BrdU than in the control group (1.46% +/- 0.96).
      Immunohistochemically, the majority of the BrdU-positive cells consisted of
      fibrocytes, smooth muscle cells, and endothelial cells. Only 0.35% +/- 0.26 of
      cardiac myocytes in the normotensive group showed positive BrdU-staining compared
      to 0.48% +/- 0.32 in the hypertensive group. This difference was statistically
      not significant. This study showed that early after onset of hypertension
      proliferation of non-myocytes, but not of myocytes occurred. DNA synthesis is
      limited almost completely to the interstitial cells and does not occur in any
      significant extent in cardiac myocytes. In conclusion, hyperplasia of cardiac
      myocytes is not observed at early stages of hypertension, but it may develop at a
      late stage of cardiac adaptation.

PMID- 8874777
TI  - Regional distribution of HSP70 proteins after myocardial infarction.
AB  - Hypoxia and altered hemodynamic status, both components of myocardial infarction,
      have been shown to be potent inducers of the 70 kD family of heat shock proteins
      (HSP70). We hypothesized that after infarction, the surviving myocardium would
      synthesize HSP70 proteins in a temporally and regionally distinct pattern. We
      believed that there would be a lack of an HSP70 response in the infarcted area
      (I), reflecting the loss of viable cells. We further postulated that tissues
      bordering infarctions (M) would have a compromised HSP70 response. Conversely, we
      proposed that HSP70 would be induced in septal tissues (S) of the infarcted
      heart, as a hypertrophic adaptation. A rat model of myocardial infarction was
      used to examine the changes in relative concentration and distribution of three
      major HSP70 family proteins; cytoplasmic HSP72, mitochondrial HSP75, and
      endoplasmic reticular GRP78 (glucose regulated protein) during 21 days of
      recovery. While all three HSP70 family proteins investigated were detected in all
      hearts from all groups at all time periods, experimental treatment (infarction)
      induced changes in relative protein concentrations that varied with time and
      sample site location. Relative concentrations of HSP72 and GRP78 were unchanged
      in the 24 h following infarction while relative HSP75 concentrations were halved
      in M tissues during the same time period. Between days 5 and 7, several changes
      were noted. M samples displayed nearly twice the relative concentrations of HSP75
      and GRP78 after infarction, but showed no change in HSP72. S tissues showed two
      fold or larger increases in all three HSP70 family proteins. I samples showed
      unanticipated increases in HSP75 and GRP78 during this time period. After 14 to
      21 days of recovery, HSP70 family protein concentration levels in M, S, and I
      tissues from infarcted hearts had returned to levels similar to those seen in
      control animals. We conclude that the myocardium is unable to, or does not, mount
      an immediate HSP70 response after infarction but does recover such activity by 5
      7 days after infarction.

PMID- 8874778
TI  - Inhibition of granulocyte-derived proteases reduces the increase in plasma
      endothelin associated with myocardial ischemia in the pig.
AB  - Plasma endothelin (ET) is increased in association with myocardial infarction.
      The aim of the present study was to get insight into the mechanisms behind this
      ischemia-induced increase in plasma ET. Since granulocytes increase ET production
      in vitro, we examined to what extent inhibition of granulocyte-derived proteases
      could reduce the increase in plasma ET observed in association with myocardial
      ischemia. We infused Eglin C, a selective inhibitor of the granulocyte-derived
      proteases elastase, cathepsin G, and chymotrypsin, in pigs subjected to 90 min
      left anterior descending coronary artery occlusion followed by 210 min
      reperfusion (n = 7). Arterial plasma ET increased in an untreated control group
      (n = 7) from 5.0 +/- 0.6 (mean +/- SEM) fmol . ml-1 before myocardial ischemia to
      6.1 +/- 0.6 fmol . ml. at 90 min ischemia and reached a maximum of 6.8 +/- 0.9
      fmol . ml-1 at 90 min reperfusion. The increase in plasma ET associated with
      myocardial ischemia was almost completely abolished in the Eglin C treated group
      (p = 0.005). Plasma ET in the Eglin C treated animals was 4.7 +/- 0.4, 4.7 +/-
      0.4, and 4.6 +/- 0.4 fmol . ml-1 before myocardial ischemia, at 90 min ischemia,
      and at 90 min reperfusion, respectively. Our study suggests a role for
      granulocyte-derived proteases in the increase in plasma ET associated with
      myocardial ischemia. We have shown that the increase in plasma ET associated with
      myocardial ischemia was reduced by inhibition of granulocyte-derived proteases
      using the selective protease inhibitor Eglin C.

PMID- 8874779
TI  - Comparison of the effects of levosimendan, pimobendan, and milrinone on canine
      left ventricular-arterial coupling and mechanical efficiency.
AB  - We examined and compared the effects of levosimendan, a new myofilament calcium
      sensitizer with phosphodiesterase inhibiting activity, pimobendan, and milrinone
      on left ventricular-arterial coupling and mechanical efficiency in 21 experiments
      performed in open-chest, barbiturate-anesthetized dogs instrumented for
      measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped
      catheter), +dP/dt, and LV volume (conductance catheter). Myocardial contractility
      was assessed with the end-systolic pressure-volume relation (Ees) and preload
      recruitable stroke work (Msw) generated from a series of differentially loaded LV
      pressure-volume diagrams. LV-arterial coupling and mechanical efficiency were
      determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of
      end-systolic arterial pressure to stroke volume) and the ratio of stroke work
      (SW) to pressure-volume area (PVA), respectively. Levosimendan (0.75, 1.5, and
      3.0 micrograms.kg-1.min-1) significantly (p < 0.05) increased heart rate, +dP/dt,
      and ejection fraction (EF) and decreased mean arterial pressure (MAP), pressure
      work index (PWI; an estimate of myocardial-oxygen consumption), and LV systolic
      and end-diastolic pressures (LVSP and LVEDP) and volumes (EDV and ESV).
      Levosimendan-induced augmentation of myocardial contractility (Ees, Msw and
      +dP/dt) and reductions in LV afterload (Ea) caused increases in the Ees/Ea ratio
      (0.61 +/- 0.10 during control to 3.3 +/- 0.7 during the high dose) consistent
      with enhancement of LV-arterial coupling. Levosimendan increased SW/PVA (0.48 +/-
      0.05 during control to 0.84 +/- 0.04 during the high dose), indicating this drug
      improves the transfer of myocardial potential energy to external work.
      Levosimendan also increased the ratio of SW to PWI (109 +/- 18 during control to
      255 +/- 50 mmHg.min.100g during the high dose), suggesting that myocardial
      metabolic efficiency was improved as well. Like levosimendan, pimobendan and
      milrinone (10, 20, and 40 and 1.0, 2.0, and 4.0 micrograms.kg-1.min-1,
      respectively) increased HR, +dP/dt, EF, Ees, and Msw and decreased MAP, LVSP,
      LVEDP, EDV, ESV, and Ea. In contrast to levosimendan, neither agent reduced PWI.
      Pimobendan and milrinone caused dose-related increases in Ees/Ea, SW/PVA, and
      SW/PWI. The results indicate that levosimendan, pimobendan, and milrinone augment
      myocardial contractility, produce venous and arteriolar vasodilation, and enhance
      LV-arterial coupling and mechanical efficiency in open-chest, barbiturate
      anesthetized dogs.

PMID- 8874780
TI  - The oxygen wasting effect of isoproterenol is altered by chemical denervation and
      cardiac hypertrophy.
AB  - We tested the hypothesis that isoproterenol would increase myocardial work and O2
      consumption at reduced efficiency and that both left ventricular hypertrophy and
      chemical sympathectomy would lead to changes in this myocardial efficiency
      response. Left ventricular hypertrophy was produced by aortic valve plication in
      23 puppies. Six months later, sympathetic denervation (6-hydroxydopamine) was
      produced in 12 hypertrophied and 10 non-hypertrophied dogs, 5 days prior to acute
      experiments. Ten non-hypertrophied and 11 hypertrophied animals were not
      denervated. Measurements were made before and during an isoproterenol infusion
      (0.5 microgram/kg/ min). Regional myocardial work was calculated as the
      integrated product of force (miniature transducer) and segment shortening
      (ultrasonic crystals). Regional O2 consumption was calculated from regional blood
      flow (microspheres) and regional O2 saturations (microspectrophotometry). In all
      groups, regional O2 consumption increased with isoproterenol (non-hypertrophied,
      non-sympathectomized 6.5 +/- 0.8 to 20.3 +/- 5 ml O2/min/100 g, non
      hypertrophied, sympathectomized 5.0 +/- 0.7 to 10.0 +/- 1.5, hypertrophied, non
      sympathectomized 9.8 +/- 1.3 to 16.2 +/- 2.2, hypertrophied, sympathectomized 6.1
      +/- 0.5 to 13.3 +/- 1.6). Regional segment work also increased in all groups with
      isoproterenol stimulation (non-hypertrophied, non-sympathectomized 781 +/- 73 to
      1197 +/- 61 g.mm/min, non-hypertrophied, sympathectomized 996 +/- 221 to 2118 +/-
      412, hypertrophied, non-sympathectomized 1031 +/- 145 to 3262 +/- 753,
      hypertrophied, sympathectomized 721 +/- 116 to 1745 +/- 402). In the non
      hypertrophied, non-sympathectomized group, efficiency (work/O2 consumption) was
      significantly decreased from 122 +/- 17 to 76 +/- 9 g.mm/ml O2/100 g
      demonstrating an "oxygen wasting" effect. In the hypertrophied, non
      sympathectomized group, segment efficiency significantly increased from 94 +/- 19
      to 250 +/- 63. In both sympathectomized groups, efficiency was not altered by
      isoproterenol. Thus the oxygen wasting effect of beta-adrenergic stimulation was
      reversed by left ventricular hypertrophy and blocked by sympathectomy.

PMID- 8874781
TI  - Contribution of the ventricles and the atrial appendages to the elevation of
      plasma atrial natriuretic factor (ANF) during pacing-induced heart failure in
      conscious dogs.
AB  - The goal of our study was to determine whether the elevation in plasma ANF was
      produced by the atrial appendages or ventricular tissue during pacing-induced
      heart failure in chronically instrumented conscious dogs (sham) or dogs with
      bilateral atrial appendectomy. Acute volume expansion caused a significant
      elevation of plasma ANF from 80 +/- 8 to 149 +/- 26 pg/ml (p < 0.01) in sham
      dogs, but caused no significant change from 67 +/- 7 to 84 +/- 8 pg/ml in atrial
      appendectomized dogs. There were increases in left ventricular end-diastolic
      pressure (LVEDP) and left atrial pressure (LAP) in both groups of dogs. After
      rapid left ventricular pacing (210-240 beats/min) for 4 weeks to induce heart
      failure, dogs in both groups had tachycardia, elevated LVEDP and higher LAP.
      Plasma ANF was increased by 250% to 283 +/- 64 pg/ml (p < 0.01) in sham dogs, and
      only 40% to 94 +/- 15 pg/ml (p > 0.05) in atrial appendectomized dogs. In
      response to volume expansion, there were further increases in LVEDP and LAP in
      both groups of dogs, but plasma ANF was not elevated (288 +/- 39 pg/ml) in sham
      dogs and only slightly increased (132 +/- 7 pg/ml) in atrial appendectomized
      dogs. Our results suggest that, during pacing-induced heart failure, the atrial
      appendages are the major source of elevated plasma ANF, and the remaining atrial
      and ventricular tissue, even when maximally stretched, can only modestly increase
      plasma ANF.

PMID- 8874782
TI  - Short- and long-term effects of nisoldipine on cardiac function and exercise
      tolerance in patients with hypertrophic cardiomyopathy.
AB  - Nisoldipine is a second generation dihydropyridine calcium antagonist having
      characteristics of strong coronary artery dilating effect and less negative
      inotropic action. The purpose of this study was to evaluate the effect of
      nisoldipine on the cardiac function (systolic and diastolic) and the exercise
      tolerance, in patients with hypertrophic cardiomyopathy (HCM). SUBJECTS: Twenty
      three patients with HCM were studied. METHODS: We measured the following indices
      using M-mode and pulsed wave Doppler echocardiography before and after
      nisoldipine therapy; left ventricular fractional shortening (LVFS), isometric
      relaxation time (IRT), deceleration half-time (DHT) of early diastolic mitral (E)
      flow, late diastolic mitral (A) flow and A/E ratio. Symptom-limited treadmill
      exercise test was performed. Exercise tolerance (EX) time was measured.
      Nisoldipine of 10 mg/day was orally administered. Same tests were repeated on day
      14 and after 6 months. RESULTS: 1) Short-term effects; LVFS did not change (55.9
      +/- 5.9%-->57.0 +/- 7.4%, NS) after 2 weeks. However, LV diastolic function
      significantly improved (IRT; 92.1 +/- 7.7 ms-->85.2 +/- 11.6 ms, p < 0.05, DHT;
      70.7 +/- 16.2 ms-->63.3 +/- 3.7 ms, p < 0.05). EX time increased (8.9 +/- 2.6 min
      ->10.0 +/- 3.3 min, p < 0.05), 2) Long-term effects; LV diastolic function had a
      tendency toward improvement, but is statistically not significant (IRT; 91.1 +/-
      7.6-->83.8 +/- 11.6 ms, DHT; 73.1 +/- 23.4-->61.0 +/- 11.4 ms, A/E; 1.26 +/- 0.29
      ->1.11 +/- 0.36) after 6 months. EX time was significantly increased (9.4 +/- 1.7
      -> 10.1 +/- 1.7 min, p < 0.05). CONCLUSIONS: Nisoldipine improved LV diastolic
      dysfunction and exercise tolerance in patients with HCM. These effects were
      similar to the first generation calcium antagonists. LV diastolic dysfunction may
      be improved due to the reduction of intracellular calcium concentration and the
      relief of myocardial ischemia by strong coronary artery dilating effect. However,
      nisoldipine did not affect the LV systolic function because of its less negative
      inotropic effect.

PMID- 8874783
TI  - Reproductive stresses in undernourished and well-nourished women.

PMID- 8874785
TI  - Nutrition during lactation.

PMID- 8874784
TI  - Nutritional studies on pregnant women in Umbria (Italy).

PMID- 8874786
TI  - Composition of human milk: nutritional aspects.

PMID- 8874787
TI  - Linear growth in children.

PMID- 8874788
TI  - Children on adult diets.

PMID- 8874789
TI  - Growth in Italian children.

PMID- 8874790
TI  - The WHO growth chart: historical considerations and current scientific issues.

PMID- 8874791
TI  - Biochemical markers of skeletal growth in children.

PMID- 8874792
TI  - Body composition of Italian children.

PMID- 8874793
TI  - Relationship of nutritional status and functional development in preschool age
      children.

PMID- 8874794
TI  - Fat nutrition during infancy and childhood.

PMID- 8874795
TI  - Energy cost of growth in infants.

PMID- 8874796
TI  - Creatine kinase: the characteristics of the enzyme regenerated from the thio
      methylated creatine kinase reflect a differentiation in function between the two
      reactive thiols.
AB  - The activity of S-thiomethyl-modified creatine kinase is due to regeneration of
      the free thiol (Hou and Vollmer, Biochim Biophys Acta (1994) 1205, 83-88).
      Characteristics of enzyme regenerated from the S-thiomethyl-modified creatine
      kinase are reported in the present study. The intrinsic fluorescence of the
      regenerated enzyme is similar to that of the native enzyme in the presence or
      absence of the dead-end complex. Regenerated CK (rCK) with full activity has only
      one reactive thiol. The rate constant of the rCK-reactive thiol reacting with
      DTNB is close to that of the slow phase of the reactive thiols of the native
      enzyme. If the IAM-modified rCK is treated with the same method as that for
      obtaining the rCK, the thiol-methylated reactive thiol of the rCK is reduced to a
      free SH and a regenerated enzyme, RCK, is produced with about 10% of the rCK
      activity. Therefore, the different roles of the two reactive thiols of creatine
      kinase may stem from the characteristics of the rCK, which suggests that only one
      of the two reactive thiols is related to the activity of the enzyme and the
      slower phase thiol (the first SH) in the modification reaction with DTNB is
      directly related to the enzymatic activity, while the faster phase thiol (the
      second SH) assists the first SH. This compensatory mechanism is proposed in the
      present study to interpret the dispute on the reactive SH role in the enzymatic
      catalysis.

PMID- 8874797
TI  - RNase E can inhibit the decay of some degradation intermediates: degradation of
      Desulfovibrio vulgaris cytochrome c3 mRNA in E coli.
AB  - In Escherichia coli, ribonuclease E (RNase E) is a key endonuclease in mRNA
      decay. We have analysed the role of E coli RNase E on the degradation of a
      heterologous cytochrome c3 (cyc) mRNA from Desulfovibrio vulgaris Hildenborough.
      The decay of the cyc transcript in wild-type and mutant E coli cells was followed
      and the degradation intermediates analysed by Northern blotting and S1 protection
      analysis. The half-life of total cyc mRNA intermediates was increased in the
      RNase E mutant. A number of degradation intermediates were stabilised, and new
      species arose. However, some species decayed faster in the met5 mutant at the non
      permissive temperature, suggesting that RNase E might inhibit their degradation.
      The results indicate that RNase E is involved in cyc mRNA degradation, and,
      interestingly, decay of certain intermediates could be reduced by this enzyme
      activity. This may suggest a functional interaction between RNase E and
      exonucleases, like polynucleotide phosphorylase.

PMID- 8874798
TI  - Regulation of metallothionein gene expression. Studies in transfected primary
      cultures of chick embryo liver cells.
AB  - To study the regulation of expression of the metallothionein gene in normal liver
      cells, we transfected chick embryo liver cells in primary cultures with
      constructs containing luciferase or chloramphenicol acetyl transferase (as
      reporter genes) under the control of differing lengths of the 5'-promoter region
      of the chick metallothionein gene (containing 30, 122, 190, or 623 base pairs
      upstream of the transcriptional start site). We controlled for efficiency of
      transfection by co-transfections with a plasmid containing a bacterial beta
      galactosidase gene under the control of the SV 40 promoter and enhancer.
      Treatment of the transfected cells with transition metallic ions (cadmium,
      cobalt, and zinc) or sodium arsenite produced increases in activities of
      luciferase or chloramphenicol acetyl transferase, relative to beta-galactosidase,
      and this activity mapped to the first 122 base pairs of the promoter. Although
      heme has recently been reported to induce the endogenous metallothionein gene in
      chick embryo liver cells, 10-50 microM heme did not increase reporter gene
      activities in transfected cells. Nevertheless, the heme-dependent induction of
      endogenous heme oxygenase-1 in these cells was normal. We conclude that the heme
      dependent induction of the liver metallothionein gene depends upon DNA region(s)
      outside the regulatory region of the chick metallothionein gene studied here and
      that elements within the first 122 base pairs of the metallothionein promoter are
      sufficient to confer responsiveness to transition metals or sodium arsenite.

PMID- 8874799
TI  - Biochemical characterization of a new disintegrin, flavostatin, isolated from
      Trimeresurus flavoviridis venom.
AB  - We biochemically characterized a new disintegrin, flavostatin, isolated from
      Trimeresurus flavoviridis venom. Flavostatin inhibited ADP-, collagen-, and
      thrombin receptor agonist peptide-induced platelet aggregation in human platelet
      rich plasma (IC50 range: 59 to 111 nM) and blocked the binding of biotinylated
      human fibrinogen to purified GPIIb/IIIa with an inhibitory potency 31,000-fold
      higher than that of Arg-Gly-Asp-Ser (RGDS). Flavostatin strongly inhibited high
      shear-stress-induced platelet aggregation in platelet-rich plasma (PRP) with an
      IC50 value of 188 nM. Fluorescein isothiocyanate (FITC)-conjugated flavostatin
      saturably bound to unstimulated and ADP-stimulated washed platelets with high
      affinity (Kd values: 38 and 21 nM, respectively); the corresponding number of
      binding sites was 86460 and 79192 per platelet. In competition experiments with
      several glycoprotein IIb/IIIa antagonists, the binding of FITC-conjugated
      flavostatin to platelets was completely inhibited by ReoPro, triflavin, TP9201,
      MK383 and GR144053, but not by YM207, YM337 and B6A3.

PMID- 8874800
TI  - Deimination of glycogen phosphorylase b by peptidylarginine deiminase. Influence
      on the kinetical characteristics and dimer-tetramer transition.
AB  - The kinetics of the native glycogen phosphorylase b from rabbit skeletal muscle
      and of the enzyme specifically deiminated by peptidylarginine deiminase have been
      studied. One arginine residue per phosphorylase b monomer is transformed into
      citrulline after 3 h of incubation with peptidylarginine deiminase. The maximal
      velocity of the enzymatic reaction for the modified phosphorylase b is 7-20%
      higher than that for the native enzyme. Deiminated phosphorylase b, like the
      native enzyme, shows a positive kinetic cooperativity with respect to glucose-1
      phosphate. The affinity of the modified phosphorylase b for the allosteric
      activator AMP is one order of magnitude higher than that of the native enzyme.
      Deimination caused a pronounced reduction of the values of [I]0.5 for FMN and
      glucose, but the sensitivity of the deiminated enzyme to glucose-6-phosphate is
      much lower than that of the native phosphorylase b. Deiminated phosphorylase b,
      unlike the native enzyme, shows the positive cooperativity for FMN binding.
      Deiminated phosphorylase b, unlike the native enzyme, shows less capability to
      form tetramers in the presence of AMP as compared to the native enzyme.

PMID- 8874801
TI  - Allosteric regulation by Mg2+ of the vacuolar H(+)-PPase from Acer pseudoplatanus
      cells. Ca2+/Mg2+ interactions.
AB  - The tonoplast H(+)-PPase was previously characterized in Acer pseudoplatanus
      cells (Pugin et al (1991) Plant Sci 73, 23-34; Fraichard et al (1993) Plant
      Physiol Biochem 31, 349-359). Tonoplast vesicles were obtained from vacuoles
      isolated from protoplasts of A pseudoplatanus suspension cultures and used to
      study kinetic effects of Mg2+ and Ca2+ on PPi hydrolysis. The concentrations of
      ionic species (free Mg2+, free PPi, and MgPPi complexes) were calculated with
      apparent dissociation constants of 55.3 microM for MgPPi and 59.6 microM for
      CaPPi. Our results indicated that the substrate of the tonoplast PPase was a
      MgPPi complex and that free Mg2+ was essential for PPi hydrolysis. With fixed
      free Mg2+ concentrations, PPase activity showed Michaelis-Menten kinetics with
      respect to MgPPi. Moreover, free Mg2+ acted as an allosteric activator with a
      Hill coefficient of 2.4, indicating at least two Mg2+ binding sites on the
      enzyme. The Mg-imidodiphosphate complex was a competitive inhibitor of the
      substrate MgPPi but did not change significantly the allosteric activation by
      free Mg2+. This result confirmed the presence of Mg2+ regulatory sites. Ca2+
      acted as an uncompetitive inhibitor of MgPPi hydrolysis. Furthermore, the
      sensitivity of the H(+)-PPase to Ca2+ increased with decrease in free Mg2+
      concentration. Therefore, Ca2+ and Mg2+ may compete for a common binding site.
      Taken together, our results confirm that activation by free Mg2+ and inhibition
      by Ca2+ could be involved in the regulation of the PPase activity in vivo.

PMID- 8874802
TI  - Inhibition studies of S-adenosylhomocysteine hydrolase purified from
      Acinetobacter calcoaceticus ULA-501.
AB  - Adenosine analogs previously reported as reversible inhibitors of mammalian S
      adenosylhomocysteine hydrolase (SAHase) have been found to exert similar effects
      on Acinetobacter calcoaceticus ULA-501 enzyme. In addition, two metal
      coordination compounds, cis-platinum diammine dichloride (cis-DDP) and its trans
      isomer (trans-DDP), the former well known for its employment in anticancer
      chemotherapy, were assayed on both bacterial and mammalian SAHases. In our
      conditions, trans-DDP appeared to be the strongest inhibitor toward both SAHases.
      Finally, treatment of the bacterial enzyme with a mixture of ATP-Mg acetate and
      KC1 caused only a slight reversible inhibition, in contrast to the complete
      inactivation exerted on the mammalian SAHase.

PMID- 8874803
TI  - Use of elastase as an internal standard in immunoblotting techniques.
AB  - A non-radioactive method for relative, semi-quantitative analysis of immunoblots,
      based on the use of elastase as internal standard and conventional peroxidase
      staining was devised and applied to the immunoassay of Gs-proteins in crude
      membrane preparations of rat kidneys. We found that the coefficients of variation
      of samples, run within the same experiment or run within different experiments,
      are reduced to half or a quarter of their original value respectively when
      corrected for elastase as an internal standard, allowing meaningful comparison of
      these samples.

PMID- 8874804
TI  - Comparative analysis of the cya locus in enterobacteria and related gram-negative
      facultative anaerobes.
AB  - Comparison of the cya loci (cya codes for adenylyl cyclase (AC)) from a variety
      of phylogenetically divergent facultative anaerobic Gram-negative bacteria
      reveals conserved sequence features. The entire locus structure in enterobacteria
      is preserved, including two major promoters (a conserved cya strong promoter, P2,
      and a divergent promoter for a heme biosynthetic operon, hemCD) present in the
      upstream region of the cya gene. The region between hemC and cya is much longer
      in Proteus mirabilis than in other enterobacteria, and lacks the P1 upstream cya
      promoter. In Aeromonas hydrophila the cya promoter (the strong P2 promoter in E
      coli) is preserved, including a putative GATC methylation site situated
      immediately downstream from the -10 box. Each cya frame analyzed uses TTG as the
      translation start codon and is preceded by an unusual ribosome binding site. This
      suggests that a lower translation efficiency of the cya transcript could be the
      result of some selection pressure. This has been substantiated by in vitro
      mutagenesis and by selection of up mutations which all map at the cya ribosome
      binding site. In enterobacteria the cyaY frame is the only conserved reading
      frame downstream of cya, with the orientation opposite to that of cya. This
      organization is not preserved in Aeromonas. Experiments involving fusions with
      the lacZ gene demonstrated that cyaY is expressed. Finally, comparison of the
      different polypeptide sequences of ACs permits discussion of important features
      of the catalytic and regulatory centers of the protein.

PMID- 8874806
TI  - Polarity of cultured newborn rat skin basal cell layer.
AB  - Basal cells were prepared from the newborn rat skin epidermis and cultured on a
      type I collagen-coated filter. This cultured basal cell layer showed an amiloride
      sensitive polarity, and the apical surface of the cell layer was more acidic than
      the basal surface. When the basal cells were cultured with ascorbic acid, a
      polarity reverse of the cultured cell layer was observed. In this case,
      synthesized and accumulated type IV collagen was detected on the whole apical
      surface of the cultured cell layer. An inhibitor of collagen synthesis, cis
      hydroxyproline (cis-OH-Pro), suppressed the ascorbic acid-induced polarity
      reversal. Furthermore, when basal cells were cultured on a type IV collagen
      coated filter, the amiloride-sensitive polarity of the cultured cell layer
      resembled the cultivation on a type I collagen-coated filter. In this case, the
      polarity was reversed by the addition of ascorbic acid, and cis-OH-Pro suppressed
      this reversal. Based on these results, we concluded that cultured skin basal cell
      layer showed an amiloride-sensitive polarity. Moreover, newly synthesized and
      accumulated type IV collagen was deduced to affect the polarity reversal in the
      cultured basal cell layer.

PMID- 8874805
TI  - Cellular antioxidant defense by a ubiquinol-regenerating system coupled with
      cytosolic NADPH-dependent ubiquinone reductase: protective effect against carbon
      tetrachloride-induced hepatotoxicity in the rat.
AB  - We found that NADPH-dependent ubiquinone reductase (NADPH-UQ reductase) in rat
      liver cytosol reduces ubiquinone (UQ) to ubiquinol (UQH2) in lipid membranes and
      consequently inhibits lipid peroxidation [Takahashi T., et al., Biochem. J., 309,
      883-890 (1995)]. Here we examined whether or not this UQH2-regenerating system
      functions as a cellular antioxidant defense in animals. Rats were given UQ-10 for
      2 weeks, and were then exposed to carbon tetrachloride (CCl4). The UQ-10
      supplement increased only in the NADPH-UQ reductase and the UQH2-10 pool of rat
      liver without any appreciable change in the levels of other antioxidant factors.
      On the other hand, CCl4 markedly increased plasma aspartate aminotransferase and
      alanine aminotransferase, liver weight and thiobarbituric acid reacting
      substances formation, which are indicators of CCl4-hepatitis, and it decreased
      the liver levels of L-ascorbic acid, reduced form of glutathione (GSH), alpha
      tocopherol, NADPH-UQ reductase and glutathione S-transferase. However, all the
      above indicators of CCl4-induced hepatitis were significantly improved in rats
      given UQ-10. Furthermore, alpha-tocopherol, but neither L-ascorbic acid nor GSH,
      was significantly saved. UQ-10 supplement also was recovered glutathione S
      transferase and NADPH-UQ reductase activities slightly. These results indicated
      that UQ-10 given to rats increased the cellular UQH2-10 pool and cytosolic NADPH
      UQ reductase activity in their livers, resulting in the inhibition of lipid
      peroxidation in the biomembranes, and consequently protected the rats from the
      CCl4-hepatotoxicity.

PMID- 8874807
TI  - Estrogen receptor-mediated transcriptional activation by 17 beta-estradiol and
      its analogs.
AB  - We investigated the effects of natural and synthetic estrogens on estrogen
      receptor-mediated signal transduction and transcription. To assess estrogen
      receptor-dependent gene expression, we constructed a reporter plasmid that can
      express the luciferase gene under the control of the estrogen-responsive element.
      A transcriptional assay was performed by transfection of the reporter plasmid
      into estrogen-responsive MCF-7 cells. Transcription was completely dependent on
      the natural estrogen, 17 beta-estradiol (E2), in a dose-dependent manner.
      Retinoic acids and other steroid hormones had no effect on gene expression. The
      effect of synthetic estrogens on estrogen receptor-mediated signal transduction
      was also examined using the specific reporter assay system. A synthetic estrogen,
      diethylstilbestrol, exhibited higher activity than E2 at lower concentrations. In
      addition, transcriptional activities of the (+)- and (-)-enantiomers of
      indenestrol A, a metabolite of diethylstilbestrol, could be distinguished using
      the reporter assay system.

PMID- 8874808
TI  - A new method for permeabilization of the plasma membrane of cultured mammalian
      cells. III. Internalization of fluorescent dextrans into cultured mammalian cells
      by vortex-stirring in the presence of high molecular weight polyacrylic acid.
AB  - Using a new technique of vortex-stirring of cells with high molecular weight
      polyacrylic acid (A-119), non-permeant fluorescein isothiocyanate-labeled
      dextrans (FDs) of various molecular weights were tested to determine the degree
      of their internalization into cultured murine leukemia L1210 cells. Flow
      cytometric analyses of the treated cells revealed that FD4 with a molecular
      weight (MW) of 4400 was incorporated in an amount 13.2 times greater than that of
      the control and that FDs with MW of 19000 and 38260 were incorporated at levels
      several times greater than control levels, by vortex-stirring cells with A-119
      for 10 s followed by maintenance at 0 degree C for 10 min. Results of the present
      study indicate that this permeabilization procedure might be useful to introduce
      poorly permeable materials into cultured mammalian cells, which would be
      beneficial in various fields of biological research.

PMID- 8874809
TI  - Substrate specificity of recombinant osteoclast-specific cathepsin K from
      rabbits.
AB  - A cDNA clone encoding the rabbit cysteine proteinase cathepsin K, which is
      predominantly expressed in osteoclasts and is closely related to cathepsins L (EC
      3.4.22.15) and S (EC 3.4.22.27) [Tezuka K., Tezuka Y., Maejima A., Sato T.,
      Nemoto K., Kamioka H., Hakeda Y., Kumegawa M., J. Biol. Chem., 269, 1106 (1994)],
      was expressed at high levels in Escherichia coli in a T7 expression system. The
      insoluble recombinant enzyme was solubilized in urea and refolded at an alkaline
      pH. Cathepsin K (37-kDa) was purified by gel filtration and its enzymatic
      characteristics were determined. The enzymatic activity of cathepsin K was
      strongly inhibited by cysteine proteinase inhibitors and its optimal pH was pH
      5.5. Synthetic substrate benzyloxycarbonyl-Phe-Arg-7-(4-methyl)coumaryl-amide,
      which is hydrolyzed by cathepsins L and S, was also cleaved by cathepsin K. On
      the other hand, benzyloxycarbonyl-Gly-Pro-Arg-7-(4-methyl)coumaryl-amide was the
      most suitable substrate for cathepsin K, but was hardly hydrolyzed by cathepsin
      L. The substrate specificity of cathepsin K, as determined using various
      chemogenic substrates, showed different characteristics from cathepsins L and S.

PMID- 8874810
TI  - Potentiation by higenamine of the aconitine-induced positive chronotropic effect
      in isolated right atria of mice: the effects of cholera toxin, forskolin and
      pertussis toxin.
AB  - Aconitine and higenamine are the major cardioactive compounds obtained from
      processed aconite. The chronotropic interaction between these two compounds was
      investigated in isolated right atria of mice. Both aconitine and higenamine
      potentiated the action of the other. Practolol (1 nM), a selective beta 1
      adrenergic antagonist, but not butoxamine (1 microM), a beta 2-adrenergic
      antagonist, blocked the potentiation by higenamine (5 nM) of the aconitine
      induced positive chronotropic effect and, at high concentrations (30 and 300 nM)
      also shifted the aconitine concentration-response curves to the right. The
      potentiating interaction between aconitine and higenamine was reversed by
      pretreating with cholera toxin (CTX) and forskolin. In CTX (100 nM, 1 h)- and
      forskolin (30 and 100 nM)-treated atria, higenamine significantly depressed the
      aconitine-induced response, which was abolished by pertussis toxin (PTX, 150
      micrograms/kg, i.p., 3 d). Neither CTX (50 and 100 nM) nor forskolin (15-100 nM)
      significantly affected the aconitine-induced positive chronotropic effect, while
      PTX (150 micrograms/kg) depressed it. These results suggest that the potentiating
      interaction between aconitine and higenamine involves "cross-talk" between the
      beta 1-adrenergic signalling pathway and Gi-protein.

PMID- 8874811
TI  - 1-[[[5-(4-Nitrophenyl)-2-furanyl]methylene]imino]-2,4-imidazolidinedione
      (dantrolene), an inhibitor of intracellular Ca2+ mobilization, impairs avoidance
      performance and spatial memory in mice.
AB  - Effects of the intracerebroventricular administration of 1-[[[5-(4-nitrophenyl)-2
      furanyl]methylene]imino]-2,4-imidazolidinedi one (dantrolene, an inhibitor of
      intracellular Ca2+ mobilization) on learning/ memory were investigated in mice
      using step-through passive avoidance and radial-arm maze tests. In the passive
      avoidance test, the administration of 6 nmol of dantrolene shortened the response
      latency in the retention test. The number of times of acquisition training
      required to achieve the criterion latency (300 s) did not change in the
      acquisition test. Ten nmol of administration of dantrolene increased the number
      of times of acquisition training required to achieve the criterion latency in the
      acquisition test and shortened the response latency in the retention test. In the
      radial-arm maze tests, 20 nmol of administration of dantrolene disrupted maze
      choice accuracy and increased error numbers. These results suggest that
      intraneuronal Ca2+ mobilization plays important roles in learning and memory.

PMID- 8874812
TI  - Anti-inflammatory activities of 70% methanolic extract from Cinnamomi Cortex.
AB  - The effects of 70% methanolic extract (CC-ext) from Cinnamomi Cortex on acute and
      chronic inflammation were investigated. CC-ext inhibited the rise in vascular
      permeability induced by acetic acid and the increase of paw edema induced by
      carrageenin in mice. It was ineffective on edema derived by histamine or
      bradykinin, and exhibited only weak inhibitory effect on the edema derived by
      serotonin. CC-ext also showed inhibitory effects on the prekallikrein enzyme
      activity and ear edema induced by arachidonic acid. It also had an inhibitory
      effect on cotton pellet-induced granuloma but showed no atrophying action against
      the adrenal or thymus glands. Little effect was shown on secondary lesions in the
      development of adjuvant-induced arthritis (the arthritis reappeared from 11 to 27
      d after injection of the adjuvant). These results suggest that some active
      component having an inhibitory effect on acute inflammation is contained in
      Cinnamomi Cortex.

PMID- 8874813
TI  - Antiinflammatory effect of Trichosanthes kirilowii Maxim, and its effective
      parts.
AB  - This study was carried out to elucidate the antiinflammatory effect of 50%
      ethanol extract obtained from the fruit of Trichosanthes kirilowii Maxm, and its
      effective parts. The cut dried fruit was separated into the whole fruit, seeds
      and remaining parts, and each part was extracted with 50% ethanol. The
      antiinflammatory activity of these extracts was investigated on acetic acid
      induced vascular permeability in mice, carrageenin-induced edema and cotton
      pellet-induced granuloma formation in rats, as well as writhing symptoms in mice.
      The whole fruit and seed extractions showed an antiinflammatory activity and
      analgesic activity, but the other part did not when given perorally. These
      results suggest that the antiinflammatory effect and analgesic effect induced by
      ethanol extract of the fruit of T. kirilowii may be due to the seeds contained in
      the fruit.

PMID- 8874814
TI  - Dissociation of insulin oligomers and enhancement of percutaneous absorption of
      insulin.
AB  - This study was designed to evaluate the percutaneous absorption of insulin in an
      attempt to develop an efficient transdermal therapeutic system (system) for the
      treatment of diabetes. First, the dissociation of porcine insulin existing mainly
      as hexamers was examined. Next, enhancement of the percutaneous absorption of the
      hormone was studied by the combined use of two or more kinds of enhancers which
      exert their enhancement effects by different mechanisms, or by preparing the
      liposomal formulation of insulin. Porcine insulin dissociated in 0.1 M glycine
      HCl buffer (pH 4.0), probably to a dimer, this being demonstrated by the notable
      attenuation of the maxima at 221 and 274 nm of the circular dichroism (CD)
      spectra. Thus, 0.1 M (or partly 1 M) glycine-HCl buffer (pH 4.0) was selected for
      the preparation of all gel formulations. The in vivo absorption of insulin
      through Wistar rat skin was estimated by blood glucose level. System 3 containing
      liposomal insulin, D-limonen and taurocholate gave the greatest hypoglycemic
      response, out of the formulations used, with its response persisting over a 10 h
      period and resulting in the highest pharmacological availability (20.7 +/- 4.6%).
      The combination of n-octyl-beta-D-thioglucoside (OTG), cineol and deoxycholate
      (system 6) or D-limonen and OTG (system 5) also produced a high hypoglycemic
      effect. The in vitro penetration of insulin was investigated using system 5 and
      6. The percutaneous penetration of insulin was demonstrated by an in vitro
      experiment, but was small in quantity. Our data present unambiguous evidence that
      this hydrophilic macromolecule was absorbed through the stratum corneum of rat
      skin under selected conditions.

PMID- 8874815
TI  - Dipalmitoylphosphatidylcholine liposomes with soybean-derived sterols and
      cholesterol as a carrier for the oral administration of insulin in rats.
AB  - Dipalmitoylphosphatidylcholine (DPPC) liposomes with a soybean-derived sterol
      mixture (SS) or cholesterol (Ch) were examined as a carrier for the oral
      administration of insulin in rats. Four kinds of liposomes were prepared:
      liposomes containing SS or Ch (molar ratio of DPPC/X = 7:2 or 7:4, X = SS or Ch),
      respectively. The pharmacological availability was greater and the lag time for
      the glucose reduction was later in the order of DPPC/SS (7:4) > DPPC/SS (7:2) >
      DPPC/Ch (7:4) > > DPPC/Ch (7:2)-liposomes. This order appears to correspond well
      with that of the rigidity of the liposomal membrane. In particular, DPPC/SS (7:4)
      liposomes reduced blood glucose levels for up to 21 h in rats after oral
      administration. The highest absolute pharmacological availability was 31.6% at a
      dose of 20.0 IU/kg of DPPC/SS (7:4)-liposomes among the liposomes in comparison
      to intravenous administration.

PMID- 8874816
TI  - Pharmacodynamics and pharmacokinetics of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) after administration of a rectal dosage vehicle.
AB  - The pharmacodynamic activities (leukopoietic effect) and pharmacokinetics of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered
      rectally in various doses as hollow-type suppositories were investigated in
      rabbits. Three kinds of rhG-CSF hollow-type suppositories were employed:
      suppository I containing rhG-CSF (100-1000 micrograms/kg) in 10 mM acetate buffer
      solution (ABS) at pH 4.0, suppository II containing rhG-CSF in ABS with alpha
      cyclodextrin (alpha-CyD) as an absorption-enhancing agent, and suppository III
      containing lyophilized rhG-CSF powder. We found that the total count of
      leukocytes in peripheral blood (total blood leukocyte count) and serum
      granulocyte colony-stimulating factor (G-CSF) concentration showed a dose
      dependent increase. Consequently, the area under the increased total blood
      leukocyte count-time curve (AUI), an index of pharmacodynamic activity, and the
      area under the serum G-CSF concentration-time curve (AUC), a pharmacokinetic
      parameter, increased with an increase in the rhG-CSF dose administered rectally.
      Good correlation was found between AUL and AUC; thus, it is concluded that an
      increase in AUC leads to an increase in the effect of rhG-CSF in inducing
      leukopoiesis in rabbits following rectal administration. We report for the first
      time the rectal absorption of rhG-CSF using a new rectal dosage vehicle (rhG-CSF
      hollow-type suppository) and its leukopoietic effect. The rhG-CSF hollow-type
      suppository is found to be a promising drug delivery system.

PMID- 8874817
TI  - Pharmacodynamic activity (leukopoietic effect) of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) after rectal administration in rabbits with
      leukopenia induced by cyclophosphamide.
AB  - The pharmacodynamic activity (leukopoietic effect) and pharmacokinetics of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered in
      various doses as hollow-type suppositories were investigated in rabbits with
      leukopenia induced by cyclophosphamide (CPA-treated rabbits). We found that serum
      granulocyte colony-stimulating factor (G-CSF) concentration was increased
      following the rectal administration of rhG-CSF. Therefore, rhG-CSF could be
      absorbed from the rectal mucosa in leukopenic rabbits who received CPA at a dose
      of 30 mg/kg/d. When rhG-CSF of at least 300 micrograms/kg was administered
      rectally once a day for 3 d in CPA-treated rabbits 1 d after the induction of
      leukopenia (the total count of leukocytes in peripheral blood [total blood
      leukocyte count] was below 5000/microliter), decreased total blood leukocyte
      count returned to the normal physiological level and a maximum (7000
      16000/microliter) was obtained 3 d after the start of the rhG-CSF multiple-dosing
      regimen. We report for the first time that rhG-CSF administered rectally induces
      leukopoiesis in CPA-treated rabbits and reduces the period of leukopenia induced
      by CPA. Thus, the rhG-CSF hollow-type suppository offers a promising means of
      reducing the risk of leukopenia, an adverse side effect of CPA therapy.

PMID- 8874818
TI  - Absorption, distribution and excretion of beta-cyclodextrin and glucosyl-beta
      cyclodextrin in rats.
AB  - The absorption, distribution and excretion of intravenously and orally
      administered beta-cyclodextrin (beta-CD) and glucosyl (G)-beta-CD in rats were
      studied using HPLC with pulsed amperometric detection. Within 10 h after
      intravenous administration, unchanged beta-CD and G-beta-CD recovered in urine
      were about 90% of each dose. The nephritic accumulation of G-beta-CD after the
      intravenous administration of G-beta-CD was slightly lower than that of beta-CD
      using the same treatment. The maximum plasma concentrations of beta-CD and G-beta
      CD after the oral administration of CDs (500 mg/kg) were observed within 40 min.
      After oral administration, 0.6% of beta-CD and 0.3% of G-beta-CD were excreted in
      urine. The pharmacokinetic behaviour of both CDs after the intravenous
      administration of CDs (50 mg/kg) was almost the same. Furthermore, the inclusion
      complexes of estriol and betamethasone with CDs were prepared, and their
      absorption was evaluated after oral administration in rats. The plasma
      concentrations of CDs after oral administration of drug-CD complexes were
      significantly decreased in comparison with those after the oral administration of
      CDs alone. On the other hand, the plasma concentrations of drugs after the oral
      administration of drug-CD complexes were higher than those after the
      administration of drugs alone.

PMID- 8874819
TI  - Pharmaceutical studies for gene therapy: expression of human Cu, Zn-superoxide
      dismutase gene transfected by lipofection in rat skin fibroblasts.
AB  - To evaluate whether lipofection using Lipofectin is suitable for delivering
      foreign genes into skin fibroblasts as target cells, we performed experiments
      using human superoxide dismutase (hSOD) and neomycin-resistance (Neo) genes as
      models in rat skin fibroblasts (FR and primary cells) in vitro. The amounts of
      DNA used in the lipofection procedure significantly affected the transfection
      efficiencies, and the optimal amounts were determined for all cells used.
      However, the efficiencies in rat skin fibroblasts were about 20-fold higher than
      that in rat lung epithelial-like cells (L2 cells). The differences in plasmid
      vectors (pRc/RSV-SOD and pRc/CMV-SOD) hardly affected the transfection
      efficiencies. The amounts of Lipofectin significantly affected the transfection
      efficiencies, and the optimal amounts were determined for both types of skin
      fibroblasts. However, cytotoxic effects in both skin fibroblasts were observed
      with high doses of Lipofectin. On the other hand, with optimal amounts of DNA and
      Lipofectin, the reporter gene (NeoT) introduced into cells was mainly integrated
      into the host cell chromosome. Western blot analysis showed the continuous
      expression of hSOD protein for at least 45 d in skin fibroblasts transfected with
      the expression plasmid for hSOD by Lipofectin under the optimal conditions, and
      the cellular SOD activity fluctuated in parallel with the expression of hSOD
      protein. Differences in the type of cells also affected the expression of hSOD.
      These results indicate that it is necessary to set up optimal conditions for
      transfection using Lipofectin for each cell type, and that transfection with
      Lipofectin under optimal conditions may be an efficient method for introduction
      of foreign genes into skin fibroblasts for use as a clinical delivery system of
      therapeutic protein.

PMID- 8874820
TI  - Determination of hemoglobin A1C in normal and diabetic mice: neonatal
      streptozotocin-induced diabetic mice and KK-Ay mice.
AB  - We have determined Hemoglobin A1C (HbA1C) in normal, neonatal streptozotocin
      induced diabetic animals (NSZ), a model of lean-type non-insulin-dependent
      diabetes mellitus (NIDDM) with hypoinsulinaemia, and KK-Ay mice, a model of obese
      type NIDDM with hyperinsulinaemia. The HbA1C of NSZ mice was slightly increased
      from 5 to 20 weeks while the HbA1C of KK-Ay mice was markedly increased from 5 to
      10 weeks. Our findings showed a difference between experimentally-induced (NSZ)
      and genetically (KK-Ay) diabetic animals.

PMID- 8874821
TI  - Enzymatic activities of several K108 mutants of ribonuclease (RNase) Rh isolated
      from Rhizopus niveus.
AB  - We previously investigated the role of the Lys108 residue of ribonuclease (RNase)
      Rh from Rhizopus niveus, and suggested that Lys108 probably acts to stabilize the
      pentacovalent intermediate, and that an Arg residue could replace the role of
      Lys108. In RNase Le2 from Lentinus edodes, a homologous enzyme of RNase Rh,
      Lys108 is replaced by Thr. In this paper, the enzymatic properties of a K108T
      mutant and its analogous enzyme, K108S, were investigated to determine the effect
      of Thr and its analog, Ser at the 108th position on enzyme activity. The
      enzymatic properties of these mutant enzymes were compared with those of other
      mutant enzymes at this position (K108M, K108A, K108L). The results showed that
      Thr and Ser could replace Lys108 but resulted in only 2-20% of the activity of
      the native enzyme depending on the substrates used.

PMID- 8874822
TI  - Clinical application of basic arginine amidase in human male urine.
AB  - Basic human urinary arginine amidase (or esterase, called BHUAE) which is only
      found in male urine, was measured from normal volunteers between the age of 4 and
      70 years using D-valyl-L-leucyl-L-arginine-p-nitroanilide as a substrate. BHUAE
      increases during early adolescence, between 8 to 17 years of age. Then, BHUAE
      decreases in the twenties and takes a certain range of value in the mature age
      group, between the late thirties and fifties. In patients with prostate cancer, a
      significant increase in BHUAE was demonstrated in comparison with the healthy
      male group (control) over 55 years old. On the other hand, patients with benign
      prostatic hypertrophy showed no significant elevation of this enzyme activity. It
      would appear that the measurement of BHUAE in urine can be used as a marker of
      prostate cancer in an advanced age group.

PMID- 8874823
TI  - Genotypes and alkaloid contents of Datura metel varieties.
AB  - Datura metel L. var. muricata (BERNH.) DANERT was found to be double recessive
      with respect to the genes concerning the color and form of the corolla by
      breeding experiments involving four varieties, i.e. var. metel (white, simple
      corolla), var. rubra (purple, simple), var. fastuosa (purple, double or triple)
      and var. muricata (white, purple). The results support the proposal by Danert and
      others that these variants should be considered as varieties or forms of a single
      species, Datura metel. The analysis of tropane alkaloids in the seeds, flowers,
      and leaves of these four varieties showed that scopolamine was always dominant
      over hyoscyamine. The range of the scopolamine content (% of dry weight) of
      seeds, flowers, and leaves was 0.294 (var. rubra)-0.631 (var. fastuosa), 0.190
      (var. metel)-0.698 (var. rubra), and 0.042 (var. rubra)-0.255 (var.metel),
      respectively. These findings proved that all the varieties, including var.
      muricata, which exhibited medium scopolamine content among the varieties, can be
      utilized as sources of scopolamine.

PMID- 8874825
TI  - Variable glyceryl dinitrate formation as a function of glutathione S-transferase.
AB  - Nitroglycerin (GTN) has been used as the drug of choice in the treatment of
      angina pectoris. It has been shown that some glutathione S-transferases (GSTs)
      catalyze the metabolic conversion from GTN to glyceryl dinitrates (GDNs). In this
      study, we examined the substrate specificity of GSTs for GTN. Alpha and mu GSTs
      were isolated from porcine liver and intestinal mucosa by means of CM-cellulose
      and glutathione-affinity column chromatography. Mu GSTs degraded GTN time
      dependently and formed 1,3-GDN in preference to 1,2-GDN as a ratio (1,2-GDN/ 1,3
      GDN) of 0.61, whereas alpha GSTs formed twice as much 1,2-GDN as 1,3-GDN. These
      results showed that two GST families participate in the metabolic conversion of
      GTN at different hydrolyzing portions of the nitrogroups.

PMID- 8874824
TI  - The necessity of adjusting the dosage of zonisamide when coadministered with
      other anti-epileptic drugs.
AB  - Zonisamide (ZNS), a new anti-epileptic drug that exhibits a wide anti-epileptic
      spectrum, is commonly prescribed concomitantly with other anti-epileptic drugs.
      The interaction between ZNS and other anti-epileptic drugs was investigated in
      epileptic patients. The steady state plasma levels of all the anti-epileptic
      drugs were measured by high-performance liquid chromatography. The concomitant
      administration of phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ)
      with ZNS significantly decreased the ratio of the steady state plasma
      concentration to the administered dose (C/D ratio) of ZNS, whereas clonazepam
      (CZP) and valproic acid (VPA) when administered concomitantly with ZNS did not
      change the C/D ratio. Significant negative correlations were observed between the
      C/D ratio of ZNS and the doses of PB, PHT, CBZ, and VPA. On the other hand, the
      ratio of the plasma concentration of carbamazepine-10,11-epoxide (CBZ-E), the
      major active metabolite of CBZ, to the plasma concentration of CBZ was
      significantly decreased by concomitant administration with ZNS, indicating that
      ZNS inhibits the metabolism of CBZ. These findings show that when ZNS is
      administered concomitantly with these anti-epileptic drugs, it is necessary to
      monitor the plasma concentration of ZNS in order to adjust its dosage.

PMID- 8874826
TI  - In vitro-in vivo correlation of pharmacodynamics of felodipine in essential
      hypertensive patients based on an ion-channel binding model.
AB  - The relationship between the plasma drug concentration and the antihypertensive
      effect of felodipine was analyzed by an ion-channel binding model which takes
      into consideration the slow association/dissociation process of a drug at the
      calcium channel. The in vitro dissociation constant (Kd) of felodipine to the
      calcium channel in the heart of rats was determined, and was compared to the in
      vivo dissociation constant (Kd,calc) estimated by the pharmacodynamic analysis of
      the concentration-effect data in Japanese essential hypertensive patients
      obtained from literature. The relative relationship between Kd and Kd,calc of
      felodipine was substantially identical with eight other calcium channel blocking
      agents reported previously. This results suggested the possibility that we can
      predict the pharmacodynamic behavior of newly developed calcium channel blocking
      agents from the in vitro Kd value and plasma concentration-time profile in human
      using the ion-channel binding model.

PMID- 8874827
TI  - Effect of transfection with a superoxide dismutase expression plasmid on
      xanthine/xanthine oxidase-induced cytotoxicity in cultured rat lung cells.
AB  - We inserted human Cu, Zn-superoxide dismutase (hSOD) cDNA into the eukaryotic
      expression plasmid (pRc/CMV) under the control of the cytomegalovirus promoter.
      The hSOD expression plasmid (pRc/CMV-SOD) was transfected in L2 cells by mean of
      lipofection. The intracellular SOD activity in pRc/CMV-SOD transfected cells (CMV
      SOD cells) was about twice that in host cells. However the level of extracellular
      SOD activity was similar in CMV-SOD and host cells. When exposed to xanthine
      (X)/xanthine oxidase (XO) to generate active oxygen species, significantly more
      CMV-SOD cells than host cells survived. The production of lipid peroxidation in
      host cells significantly increased in the presence of X/XO, but that in CMV-SOD
      cells did not change. Thus, transfection with SOD gene effectively prevented X/XO
      induced cytotoxicity. The results indicated that increasing the level of
      intracellular SOD activity protected cells against extracellular superoxide anion
      stress.

PMID- 8874828
TI  - Effect of CYP2C polymorphisms on the pharmacokinetics of phenytoin in Japanese
      patients with epilepsy.
AB  - We examined the effect of CYP2C9/19 polymorphisms on the pharmacokinetics of
      phenytoin in 17 Japanese patients with epilepsy. The maximal elimination rate
      (Vmax) of phenytoin was slightly decreased (up to 14%) in patients with CYP2C19
      mutations for the defective allele. The Vmax values in patients with a CYP2C9
      mutation for the heterozygous Ile/Leu359 allele were 40% lower than those in
      patients with wild-type CYP2C9 for the homozygous Ile359 allele. These findings
      suggested that the genetic polymorphism of CYP2C isoenzymes plays an important
      role in the pharmacokinetic variability of phenytoin, and that the mutation in
      CYP2C9 proteins is a determinant of impaired metabolism of the drug.

PMID- 8874829
TI  - Effect of 3-deoxyglucosone on the activities of enzymes responsible for glucose
      metabolism in mouse liver.
AB  - Crude extracts containing the enzymes obtained from mouse liver were incubated
      with 3-deoxyglucosone (3-DG), and then subjected to assay of the activities of
      enzymes responsible for glucose metabolism. Hexokinase and glucose-6-phosphate
      dehydrogenase activities were decreased by 3-DG and hexokinase activity was
      strongly inhibited time and concentration dependently, while glucokinase, glucose
      6-phosphatase, and phosphofructokinase activities were scarcely affected. These
      results suggest that 3-DG inhibits the intake of glucose in the liver and a
      connection with development of diabetes.

PMID- 8874830
TI  - Inhibition of anandamide amidase activity in mouse brain microsomes by
      cannabinoids.
AB  - Mouse brain microsomes contain an amidase that catalyzes the hydrolysis of N
      arachidonylethanolamide to arachidonic acid and ethanolamine. The enzymatic
      activity is dependent on the protein concentration of the microsomes and observed
      over a wide range of pH, 7.4 to 9.5. Kinetic analysis indicated that K(m)
      (microM) and Vmax (nmol/min/mg protein) were 17.7 +/- 4.1 and 1.81 +/- 0.32,
      respectively. Cannabidiol (CBD), cannabinol (CBN) and delta 9
      tetrahydrocannabinol (delta 9-THC) significantly inhibited the hydrolysis of the
      amide by mouse brain microsomes. At a concentration of 160 microM, the inhibitory
      potency decreased in the following order, CBD (66%) > CBN (46%) > delta 9-THC
      (31%).

PMID- 8874831
TI  - Quantitative evaluation of passive cutaneous anaphylaxis (PCA) using a hand-held
      spectrophotometer.
AB  - A hand-held spectrophotometer was used for the quantitative evaluation of PCA
      caused by anti-TNP-IgE and TNP-BSA. A good relationship existed between the
      dilution of sera and the value of delta E*ab (a numerical expression of color)
      obtained by a hand-held spectrophotometer. In addition, the value of delta E*ab
      and the amount of Evans blue measured by the conventional colorimetric method
      correlated well. Because the method using a hand-held spectrophotometer provides
      a simple and objective analysis, it appears that the method is suitable as a
      substitute for the conventional method, which is time-consuming and requires
      killing animals cruelly.

PMID- 8874832
TI  - Genetic discoveries in human behavior: small effect genes loom large.

PMID- 8874833
TI  - The biobehavioral consequences of psychogenic stress in a small, social primate
      (Callithrix jacchus jacchus).
AB  - The biobehavioral consequences of psychogenic stress were examined using
      neuroendocrine and ethological methods in a captive colony of common marmosets
      (Callithrix jacchus jacchus). Specifically, hypothalamic-pituitary-adrenal (HPA)
      axis reactivity was evaluated as a function of gender and social status in four
      consecutive social environments [(1) stable heterosexual pairs; (2) isolation;
      (3) unstable peer groups; and (4) stable peer groups], by measuring both basal
      plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin
      concentrations and responsiveness of these hormones to dexamethasone, ovine
      corticotropin-releasing hormone (oCRH), and ACTH1-24. Socially stressful
      conditions, such as isolation and peer group formation, were associated with
      increased HPA axis function and behavioral arousal, and individual profiles were
      related to gender and social status. Hormonal levels prior to group formation
      predicted subsequent status in peer groups. Basal morning concentrations of
      plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression,
      were sensitive indices of HPA axis arousal during periods of social stress. The
      context-dependent development of hormonal and behavioral profiles, reminiscent of
      depression and/or anorexia nervosa, suggests that the common marmoset may be a
      useful model of psychiatric hypercortisolism.

PMID- 8874834
TI  - Rearing experience and biogenic amine activity in infant rhesus monkeys.
AB  - In this report we present evidence that early social experience influences
      aspects of the function of brain biogenic amine systems, most notably the
      noradrenergic system. Biogenic amine activity was studied in mother- vs. peer
      reared monkey infants over the first 6 months of life and in response to two
      housing transitions. Norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG),
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5
      hydroxyindoleacetic acid (5-HIAA) levels in cerebrospinal fluid (CSF) were
      measured. Peer-reared monkeys showed significantly higher CSF levels of
      norepinephrine and MHPG than mother-reared animals over early development, but
      showed an attentuated NE response to separation and group formation compared to
      mother-reared animals. Peer-reared monkeys showed a greater developmental decline
      in 5-HIAA levels than mother-reared monkeys. There were no rearing effects for
      DOPAC or HVA over early development; however, peer-reared monkeys showed
      significantly lower HVA and DOPAC concentrations at 6-8 months of age. The
      results add to evidence for the influence of primate mothers on the
      psychobiological development of central nervous system neurotransmitter systems
      in their infants, and suggest that the noradrenergic system is among the more
      sensitive of these to early experience.

PMID- 8874835
TI  - Cardiovascular, neuroendocrine, and monoaminergic responses to psychological
      stressors: possible differences between remitted panic disorder patients and
      healthy controls.
AB  - Both clinical symptomatology and stress research suggest that panic attacks might
      be partially attributable to exaggerated psychophysiological responses to
      environmental stressors. In the present study, we aimed to explicitly test this
      idea by measuring the physiological responses to a mild psychological stressor in
      both healthy controls (n = 8) and fully remitted, medication-free panic disorder
      patients (n = 8). One hour before the stressor, former patients, compared to
      healthy controls, exhibited higher diastolic blood pressure. From a blood sample
      taken 30 min before the stressor, patients, compared to controls, had lower
      paroxetine platelet binding site densities. During the stressor, patients,
      compared to controls, had greater increases in plasma levels of cortisol. These
      preliminary findings suggest that remitted panic disorder patients might have
      disturbed physiological responses to mild psychological stressors. These
      disturbances might be related to the development of future episodes.

PMID- 8874836
TI  - Fluoxetine treatment alters leukocyte trafficking in the intrathecal compartment
      of the young primate.
AB  - To evaluate possible long-term effects of exposure to monoaminergic drugs, blood
      and cerebrospinal fluid (CSF) samples were collected from adolescent monkeys that
      had been treated with desipramine and fluoxetine in infancy. This evaluation
      focused on the number and type of leukocytes in CSF as a reflection of cell
      trafficking in the intrathecal compartment. Monkeys administered fluoxetine 2
      years prior to the sample collection evinced significantly higher numbers of
      leukocytes in CSF than did either control or desipramine-treated subjects. The
      elevated cell count was accounted for primarily by increased numbers of CD4+ and
      CD8+ lymphocytes. The finding of higher cell numbers in CSF was replicated in a
      second sample from the fluoxetine-treated monkey obtained 1.5 years later.
      Because the cell profile in blood was unaffected by the prior drug treatments,
      these observations indicate a need for further study of serotonergic influences
      on regulation of the intrathecal compartment in the developing individual.

PMID- 8874837
TI  - Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress
      disorder: a study and replication.
AB  - Subjects on an addiction treatment unit who had been exposed to severe combat
      conditions in Vietnam were screened for posttraumatic stress disorder (PTSD). Of
      24 with PTSD, 58.3% carried the D2A1 allele. Of the remaining eight who did not
      meet PTSD criteria, 12.5% carried the D2A1 allele (p = 0.04). In a replication
      study of 13 with PTSD, 61.5% carried the D2A1 allele. Of the remaining 11 who did
      not meet criteria for PTSD, 0% carried the D2A1 allele (p = 0.002). For the
      combined group 59.5% of those with PTSD carried the D2A1 allele versus 5.3% of
      those who did not have PTSD (p = 0.0001). These results suggest that a DRD2
      variant in linkage disequilibrium with the D2A1 allele confers an increased risk
      to PTSD, and the absence of the variant confers a relative resistance to PTSD.

PMID- 8874838
TI  - Event-related potentials in post-traumatic stress disorder of combat origin.
AB  - Visual event-related potentials (ERPs) of primary interest in this study of post
      traumatic stress disorder (PTSD) were N1, N2, P2, and P3. Forty Israeli combat
      veterans consisting of 20 PTSD sufferers and 20 normal controls were evaluated.
      ERPs were recorded in response to three sets of computer-generated visual
      stimuli, presented in the form of a modified oddball paradigm. These stimuli
      included: domestic animal pictures (targets), emotionally neutral pictures of
      furnishings (nontargets), and combat-related pictures (nontarget probes).
      Subjects were required to discriminate between target and nontarget stimuli by
      pressing a button in response to target stimuli only. Subjects were instructed to
      ignore all nontarget stimuli. As expected, target stimuli evoked accentuated P3
      amplitudes in both controls and PTSD patients. The nontarget combat-related
      pictures elicited enhanced P3 and N1 amplitudes in the PTSD patients only. N2
      amplitudes were accentuated in PTSD patients for both targets and combat-related
      pictures. P3 latencies and reaction times to target stimuli were prolonged in
      PTSD patients. The same tendency was observed for N1 latencies. These results may
      indicate that an altered state of early and late cognitive selective attention
      processing exists in PTSD patients in addition to a vulnerability to traumatic
      reminiscences.

PMID- 8874839
TI  - Choline in the treatment of rapid-cycling bipolar disorder: clinical and
      neurochemical findings in lithium-treated patients.
AB  - This study examined choline augmentation of lithium for rapid-cycling bipolar
      disorder. Choline bitartrate was given openly to 6 consecutive lithium-treated
      outpatients with rapid-cycling bipolar disorder. Five patients also underwent
      brain proton magnetic resonance spectroscopy. Five of 6 rapid-cycling patients
      had a substantial reduction in manic symptoms, and 4 patients had a marked
      reduction in all mood symptoms during choline therapy. The patients who responded
      to choline all exhibited a substantial rise in the basal ganglia concentration of
      choline-containing compounds. Choline was well tolerated in all cases. Choline,
      in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid
      cycling patients in our series. A hypothesis is suggested to explain both lithium
      refractoriness in patients with bipolar disorder and the action of choline in
      mania, which involves the interaction between phosphatidylinositol and
      phosphatidylcholine second-messenger systems.

PMID- 8874840
TI  - Low birth weight and neurocognitive status at six years of age.
AB  - We examined the relationship between low birth weight (LBW) (< or = 2500 g) and
      specific neurocognitive abilities at 6 years of age in a large-scale
      nonconcurrent prospective study. In 1990-1992, we randomly selected and evaluated
      LBW and normal birth weight (NBW) children from the 1983-1985 newborn lists of
      two major hospitals in southeast Michigan, one serving an urban and the other a
      suburban population. LBW children (n = 473) scored significantly lower than NBW
      children (n = 350) on tests measuring language, spatial, fine motor, tactile, and
      attention abilities, controlling for population site, race, maternal IQ, and
      education. Gradient relationships were observed across levels of LBW with
      language, spatial, tactile, and attention tests. Exploratory analysis, using
      general additive models, revealed that test performance varied within birth
      weight levels and that performance continued to improve with increased birth
      weight well above 3000 g. Follow-up assessments as the children mature will shed
      light on the persistence of these associations and their implications for
      learning disorders.

PMID- 8874841
TI  - Tryptophan depletion in obsessive-compulsive patients.
AB  - Twelve patients with obsessive-compulsive disorder were studied after the
      administration of a mixture of amino acids devoid of tryptophan (TRP) or a
      mixture containing all the essential amino acids, in a double-blind, crossover
      design. The TRP-free mixture caused a marked depletion of plasma TRP. After TRP
      decrease, mean ratings of obsessions and compulsions, measured by Visual Analogue
      Scales (VAS) ratings, did not worsen. In contrast with other reports in
      literature, TRP depletion also failed to alter mood in our subjects.

PMID- 8874842
TI  - Prolactin and TSH responses to TRH and to ECT in pre- and postmenopausal women
      with major depression.
AB  - The patterns of prolactin and thyrotropin (TSH) release after thyrotropin
      releasing hormone (TRH) (0.4 mg i.v.) and during the first session of a course of
      electroconvulsive treatment (ECT) were studied in women with major depression, 16
      in pre- and 29 in postmenopausal status. The prolactin responses to both stimuli
      were lower in postmenopausal women, whereas the TSH responses were not different.
      The known correlation between the maximal prolactin response to ECT and the
      maximal response to TRH was significantly stronger in the group of premenopausal
      women (r = .8648, versus .4249 in the postmenopausal group, p < .02). A common
      underlying mechanism promoting prolactin release for both stimuli can be
      suggested, which diminishes after menopause, probably an influence of estradiol
      on the affinity of dopaminergic and serotonergic receptors. That mechanism does
      not interfere with the TSH release either by ECT or by TRH.

PMID- 8874843
TI  - Prospective study of FK506 side effects: anxiety or akathisia?
AB  - FK506 is a macrolide immunosuppressant agent used in solid organ and bone marrow
      transplantation and for autoimmune disorders. FK506 is reported to have a number
      of neuropsychiatric side effects, including anxiety and tremor. Because FK506 was
      implicated in causing akathisia in a case report, we did a prospective, cross
      sectional study of 25 renal transplant recipients to determine whether akathisia
      occurred and/or had a relationship to FK506 plasma levels. The Symptom Checklist
      90-R, Hamilton Anxiety (HAM-A), and Akathisia Rating (ARS) scales were
      administered. Higher FK506 plasma levels correlated with higher HAM-A scores. ARS
      scores did not correlate with FK506 plasma levels; however, when FK506 plasma
      levels were divided into "high" (> or = 0.9 ng/mL) and "low" (< 0.9 ng/mL)
      groups, total ARS and HAM-A scores were significantly higher in the "high" group.
      We discuss implications of these findings as well as management.

PMID- 8874844
TI  - TRH stimulation and dexamethasone suppression in borderline personality disorder.
AB  - The link between borderline personality disorder (BPD) and affective disorders is
      controversial. The dexamethasone suppression test (DST) and the thyrotropin
      releasing hormone (TRH) stimulation test, which are useful in the study of
      affective illness, might help to elucidate this possible link. This report
      assessed these endocrine tests in a sample of 20 borderline patients without a
      concomitant diagnosis of major depression (but showing depressive symptoms) in
      comparison to a group of sex- and age-matched patients with major depressive
      disorder (MDD) without BPD. Only 5 of our BPD patients were DST nonsuppressors
      compared to 13 MDD patients at a threshold of 50 micrograms/L. With a threshold
      of delta max TSH < 5 microU/mL following TRH, 1 BPD patient showed a blunted TSH
      response compared to 9 MDD patients. BPD patients displayed significantly less
      perturbed tests. These results show no evidence of an endocrine biological link
      between BPD and the MDD. The depressive symptoms observed in BPD patients might
      not have the same biological substrates as those found in patients with MDD.

PMID- 8874845
TI  - Association study between dopamine D1, D2, D3, and D4 receptor genes and
      schizophrenia defined by several diagnostic systems.

PMID- 8874846
TI  - A case of REM sleep behavior disorder with autopsy-confirmed Alzheimer's disease:
      postmortem brain stem histochemical analyses.

PMID- 8874847
TI  - Acute inositol induces anxiety in rats.

PMID- 8874848
TI  - The thyroid, magnesium and calcium in major depression.

PMID- 8874849
TI  - Osteoporosis demonstrated by dual energy x-ray absorptiometry in chronic
      schizophrenic patients.

PMID- 8874850
TI  - Neuroleptic malignant syndrome and catatonia: one entity or two?

PMID- 8874851
TI  - Monoamine oxidase, tobacco smoking, and psychiatric disorders.

PMID- 8874852
TI  - Seroquel and cognitive improvement in patients with schizophrenia.

PMID- 8874853
TI  - Evaluation of preparation, staining and microscopic techniques for counting
      incremental lines in cementum of human teeth.
AB  - Apposition of cementum occurs in phases resulting in two types of layers with
      different optical and staining properties that can be observed by light
      microscopy. Narrow, dark staining incremental lines are separated by wider bands
      of pale staining cementum. The distance from one line to the next represents a
      yearly increment deposit of cementum in many mammals, and counting these lines
      has been used routinely to estimate the age of the animals. Incremental lines in
      cementum have also been observed in sections of human teeth, and the object of
      the present investigation was to examine a number of methods for preparing and
      staining them for counting. Longitudinal and transverse sections, either ground
      or decalcified, were cut from formalin fixed human dental roots, paraffin
      embedded or frozen, and stained using several techniques. The cementum was
      investigated using conventional light, fluorescence, polarized light, confocal
      laser scanning, interference contrast, phase contrast, and scanning electron
      microscopy. Incremental lines in the cementum could be observed in ground
      sections and, following decalcification, in both frozen and paraffin embedded
      sections. Toluidine blue, cresyl violet, hematoxylin, or periodic acid Schiff
      (PAS) stained incremental lines allowing differentiation by conventional light
      microscopy. Contrast was best using fluorescence microscopy and excitation by
      green light since the stained cemental bands, but not the incremental lines,
      fluoresced after staining with cresyl violet, PAS or hematoxylin and eosin. The
      results with other microscopic techniques were unsatisfactory. Since incremental
      lines are not destroyed by acids and stain differently than the remaining
      cementum, it is likely that they possess an organic structure which differs from
      the cementum. Incremental lines in human dental cementum could be observed best
      using decalcified sections stained with cresyl violet excited by green light.

PMID- 8874854
TI  - Acidification and recovery results in nuclear accumulation of supravital dyes
      during interphase.
AB  - Recent studies using real time imaging demonstrated relative nuclear insulation
      for ion-size particles. We show here that acidification and recovery converted
      the insulated interphase nuclei of KB carcinoma and nontumorigenic Chang cells
      into intense nuclear accumulating states marked by sequestration of the exogenous
      supravital dyes neutral red, methylene blue, and brilliant cresyl blue. The
      phenomenon was not affected by Na(+)-free and HCO3(-)-free conditions nor by the
      presence of cationic and anionic antiport regulators of cytosolic pH.
      Cytological, microspectrophotometric, and flow cytometric evaluation of whole
      cell populations showed that the nuclear influx was abolished by omitting the pH
      recovery response, and by modulating the recovery response. The abolition of
      nuclear influx in the presence of the P-ATPase and Fzero-ATPase inhibitors,
      vanadyl(IV) ions and oligomycin, respectively, suggest that H(+)-translocating
      ATPase pumps are involved in regulating cytosolic acidification in Na(+)-free and
      HCO3-conditions vanadyl(IV) inhibited nuclear uptake of supravital dyes in a dose
      dependent manner. Nuclear uptake of dyes, however, was not affected by up to 1 mM
      of genistein even though tyrosine-specific phosphorylation and DNA synthesis were
      abolished. Upgradient nuclear influx involving proton pump is novel. KB cancer
      cells and nontumorigenic Chang cells had differential dye accumulations induced
      by acidification and recovery.

PMID- 8874855
TI  - Age associated changes in the distribution of lpr gene-induced B220-positive T
      cells in lymphoid organs of MRL/Mp-lpr/lpr mice using dual exposure
      microphotographs of double immunofluorescence staining.
AB  - Homozygous MRL/Mp-lpr/lpr [MRL/lpr] mice, which have an autosomal recessive
      mutant lpr gene and exhibit defects in Fas antigen, spontaneously develop
      autoimmune disease with progressive expansion and accumulation of characteristic
      abnormal CD4-CD8-double negative T cells that express B220 surface antigen, a B
      cell-specific surface marker in normal mice. We analyzed the distribution and age
      related changes of lpr gene-induced abnormal T cells (B220-positive lpr T cells)
      in the lymphoid organs of MRL/lpr mice. We studied cryostat sections of the
      spleen, peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches at
      different stages using FITC [fluorescein isothiocyanate)-conjugated monoclonal
      antibodies directed against B220 (RA3-6B2) and PE (phycoerythrin)-conjugated anti
      mouse CD3 (2C11) monoclonal antibody, examining dual-exposure microphotographs of
      double-immunofluorescence stained preparations. We observed that in aged MRL/lpr
      mice, B220-positive abnormal lpr T cells were not present in the thymus-dependent
      area, and the majority of the follicular area cells were displaced by lpr T
      cells. These findings suggest that the cellular trafficking of B220-positive lpr
      T cells differs from that of conventional T cells and that these lpr-derived T
      cells play a role in the follicle.

PMID- 8874856
TI  - Use of pH 9.5 Tris-HCl buffer containing 5% urea for antigen retrieval
      immunohistochemistry.
AB  - Successful antigen retrieval (AR) immunohistochemistry is dependent on the
      temperature, heating time, and pH value of the AR solutions. There is no single
      standardized AR solution, however, that is suitable for all antibodies
      "routinely" used in surgical pathology for immunostaining archival tissue
      sections. We tested a variety of AR solutions varying in pH value, chemical
      composition, and molarity. Based upon preliminary results, we compared three AR
      solutions: 0.1 M Tris-HCl buffer, pH 9.5, containing 5% urea, 0.1 M Tris-HCl
      buffer pH 9.5 without urea, and citrate buffer, pH 6.0. Each AR solution was
      tested with a panel of 34 antibodies using microwave heating for antigen
      retrieval. The heating conditions were standardized at 10 min and an automated
      stainer was used to standardize the immunostaining method. The Tris-HCl
      containing urea was superior to pH 6.0 citrate buffer for 22 antibodies. In 12
      cases, Tris-HCl with urea was also superior to Tris-HCl alone. In 12 cases, the
      intensity was similar for all three retrieval solutions. The staining obtained
      with Tris-HCl with urea was equal to or better than with pH 6.0 citrate buffer in
      all cases. The Tris-HCl with urea solution is satisfactory for AR of most
      antibodies employed in routine surgical pathology.

PMID- 8874857
TI  - Cytochemical assay for differential respiratory activity in roots and root hairs.
AB  - The study of the underground parts of plants is often difficult, and as a result
      roots are often treated as homogeneous physiological entities with respect to
      root respiration. In this study we demonstrate a partitioning of respiration
      within root tissues using nitro blue tetrazolium staining and an incident light
      optical system that permits detailed observations of intact roots. The assay is
      rapid and easy to perform, and reveals that respiratory activity in roots is not
      uniform in space and time. The results show that root hairs in particular may be
      regions of enhanced respiratory activity in some species or in certain
      developmental or physiological states. This fact has important implications for
      the role of root hairs in the overall respiratory budget of roots and the
      energetics of nutrient assimilation. The results suggest that root respiration
      studies should consider differential respiratory activities of root cell types
      within roots.

PMID- 8874858
TI  - Morphological analysis of an isolated fraction containing secretory granules from
      the submandibular gland of Trypanosoma cruzi infected and normal rats.
AB  - Normal and Trypanosoma cruzi infected submandibular glands from 42 male Holtzman
      rats were homogenized in 340 mM sucrose and 0.5 mM EDTA in 10 mM HEPES buffer at
      pH 7.4. The extract was centrifuged and filtered to prepare a granule rich
      fraction. Isolated secretory granules are similar morphologically to granules
      observed in whole submandibular gland preparations. Our results suggest that our
      isolation technic can be used for morphological and biochemical studies.

PMID- 8874859
TI  - RT-PCR analysis of MMP-9 expression in human articular cartilage chondrocytes and
      synovial fluid cells.
AB  - This report presents a method for analyzing matrix metalloproteinase-9 (92 kD
      gelatinase) MMP-9 mRNA expression using reverse transcription polymerase chain
      reaction (RT-PCR). With this method, chondrocytes isolated from small samples of
      osteoarthritic cartilage showed significantly elevated signal for MMP-9 mRNA
      compared to normal cartilage. In addition, cells of synovial fluid samples
      aspirated from osteoarthritic joints also exhibited MMP-9 expression using this
      technique. RT-PCR proved to be a sensitive method for assessing MMP-9 regulation
      in osteoarthritic and normal cartilage, and may provide a useful index of
      arthritic cartilage and synovial fluid cell metabolism when limited tissue is
      available.

PMID- 8874860
TI  - Optimal duration of oral anticoagulant therapy following deep vein thrombosis of
      lower limbs.
AB  - Deep vein thrombosis of the lower limbs is usually treated with an initial course
      of heparin or low-molecular-weight heparin associated with oral anticoagulants
      which are started simultaneously, thereby allowing heparin to be stopped after 4
      7 days. Although consensus conferences have proposed a uniform duration of oral
      anticoagulant therapy of 3 months, great uncertainties remain as to the optimal
      treatment duration in an individual patient. Two large-scale studies have
      recently demonstrated that short treatment durations (4 weeks or 6 weeks,
      respectively) are associated with about two-fold higher rates of thromboembolic
      recurrences over follow-up periods of 1-2 years compared with longer treatment
      durations (3 months or 6 months, respectively). However, because treatment
      duration is also a major determinant of the hemorrhagic risk on oral
      anticoagulants, it is essential to balance the protective effect of these agents
      against their bleeding risk. This paper reviews the literature on the
      antithrombotic effects and hemorrhagic risks of different durations of oral
      anticoagulant therapy following lower limb deep vein thrombosis and suggests
      tentative recommendations which range from a short anticoagulant course of 4
      weeks in a patient with a low risk of thromboembolic recurrence and a high
      hemorrhagic risk (e.g. postoperative distal vein thrombosis) to 6 months or more
      in a patient with a low hemorrhagic risk and a high risk of thromboembolic
      recurrence (e.g. idiopathic proximal vein thrombosis in a patient with inherited
      thrombophilia or malignancy).

PMID- 8874861
TI  - A proposed model to monitor heparin therapy using the concentrated thrombin time
      which allows standardisation of reagents and improved estimation of heparin
      concentrations.
AB  - The concentrated thrombin time (CTT), a thrombin time performed with a high
      concentration of thrombin, was evaluated as an alternative to the activated
      partial thromboplastin time (APTT) for monitoring of heparin therapy. Forty-nine
      plasmas from patients receiving unfractionated heparin therapy were tested. It
      was first demonstrated that CTTs using three commercial reagents could be
      standardised against CTTs performed with a reference reagent, MRC reagent 66/305.
      For comparison, APTTs were performed on the plasmas. As a benchmark of the degree
      of heparinisation, the heparin concentration of the plasmas was determined by
      chromogenic anti-IIa heparin assays, therapeutic range being 0.2-0.4 units/ml.
      The optimal relationships of the CTTs and APTT with the heparin concentration
      were established. These were used to predict the heparin concentrations of the
      plasmas from the results of the APTT, CTT performed with the reference reagent,
      and transformed CTT performed with each of the three commercial reagents. In
      predicting the assayed plasma heparin concentrations, the accuracy of the APTT
      was only 53%, while the CTT was from 78 to 82%. The CTT can be standardised and,
      subject to results of clinical trials, could provide an improved method of
      monitoring heparin therapy.

PMID- 8874862
TI  - Effects of endothelial cells on activity of staphylokinase.
AB  - Staphylokinase (SAK), produced by Staphylococcus aureus, induces fibrinolytic
      activity in circulation without systemic fibrinolytic activation. Since the
      effect of blood vessels on the activity of SAK has not yet been clarified,
      plasminogen activator (PA) activity of SAK in the presence or absence of
      endothelial cells was analyzed. The endothelial cells used in this experiment
      were of a cloned established cell line (TKM-33). In the expression of PA activity
      by SAK or streptokinase (SK), the kinetic constants revealed as Vmax/km were
      increased about 1.5-fold in the presence of endothelial cells. Furthermore, an
      initial lag phase which was observed during the plasminogen activation by SAK was
      markedly shortened in the presence of endothelial cells. In the case of SK, an
      initial lag phase was not observed in the absence or presence of endothelial
      cells. Although PA activity of SAK was inhibited by alpha 2-antiplasmin (alpha 2
      AP), the inhibitory effect of alpha 2-AP in the presence of endothelial cells was
      weaker than in the absence of endothelial cells. The cyanogen bromide digested
      fibrinogen fragment-2 (FCB-2) distinctly enhanced the PA activity of SAK in the
      absence and the presence of endothelial cells. However, alpha 2-AP and FCB-2 did
      not cause a significant alteration of PA activity of SK even in the absence or
      presence of endothelial cells. These findings suggest that PA activity of SAK is
      enhanced by endothelial cells, but inhibited by alpha 2-AP. Moreover, PA activity
      of SAK is further enhanced by fibrin clot in the presence of endothelial cells.

PMID- 8874863
TI  - Measurement of activated factor XII in health and disease.
AB  - We investigated a new ELISA for measuring activated factor XII (FXIIa) in plasma.
      The intra-assay coefficient of variation was 3.5% and 5.1% for plasma containing
      2.5 and 8.2 ng/ml FXIIa. The inter-assay coefficient of variation was 6.2% and
      6.6%. FXIIa correlated with age in women older than 55 years (r = 0.55, P =
      0.0003). Mean levels in the whole population of 160 healthy individuals included
      in this study were not different between men and women, but women younger than 55
      years had lower levels than older women and men of the corresponding age. In a
      group of 25 healthy centenarians FXIIa was significantly higher (3.2 ng/ ml, 95%
      CI 2.3-3.6) than in controls (2.1 ng/ml, 95% CI 1.8-2.4). Increased levels were
      also found in pregnancy, with higher levels in the third trimester (4.7 ng/ml,
      95% CI 3.9-5.5) than in the first trimester (2.9 ng/ml, 95% CI 2.2-3.9). FXIIa
      was unmeasurable in patients with FXII deficiency, but normal in patients with
      FXI deficiency and C1-inhibitor deficiency. FXIIa was significantly higher than
      in normal controls in patients with severe sepsis (3.9 ng/ml, 95% CI 2.8-5.4) and
      septic shock (5.4 ng/ml, 95% CI 3.7-7.7). After treatment with thrombolytic
      agents, a marked increase of FXIIa was found in patients with myocardial
      infarction. In conclusion, the immunoassay of FXIIa permits to study more
      directly the contact phase of blood coagulation in situations in which the
      involvement of this system may play a pathophysiological role.

PMID- 8874864
TI  - Fibrin deposition in primary and metastatic human brain tumours.
AB  - Extravascular, intratumoral fibrin deposition is frequently observed within and
      around neoplastic tissue and has been implicated in various aspects of tumour
      growth. This is the first report on the presence and distribution of
      fibrinogen/fibrin in primary (14 glioblastomas) and metastatic (nine samples of
      lung cancer origin) human brain tumours detected by immunofluorescent techniques.
      All tissue samples showed specific staining for fibrinogen/fibrin. In
      glioblastomas fibrin deposits could be detected within and around tumour foci,
      while in metastatic brain tumours the tumour cell nodules were surrounded by
      fibrin deposits localized almost exclusively in the connective tissue compartment
      of tumours. Double-labelling reactions for von Willebrand factor and
      fibrinogen/fibrin has revealed that fibrin deposition occurred throughout the
      tumour stroma independently of tumour vasculature. The overlapping reactions for
      fibrinogen/fibrin and factor XIII subunit A, as well as the urea-insolubility of
      the deposits indicate the crosslinked, highly stabilized nature of fibrin both
      within and around tumours. Staining with Ki M7 monoclonal antibody specific for
      phagocytosing macrophages showed these cells to be scattered in the nonnecrotic
      areas in glioblastomas and to be accumulated at the interface of tumorous
      parenchyma and connective tissue in both primary and metastatic tumours. The
      close association between fibrin deposition and macrophage accumulation strongly
      suggests the active participation of tumour associated macrophages in the
      formation of stabilized intratumoral fibrin network in human brain neoplasms.

PMID- 8874865
TI  - DDAVP infusion in haemophilia A carriers: different behaviour of plasma factor
      VIII and von Willebrand factor.
AB  - 1-desamino-8-D-arginine vasopressin (DDAVP) increases factor VIII (FVIII) and von
      Willebrand factor (vWF) levels in patients with haemophilia A and in some
      patients with von Willebrand disease. It is generally held that the increase of
      FVIII is a consequence of the increase of vWF. Carriers of haemophilia A
      generally, but not always, show plasma FVIII levels lower than vWF due to an
      abnormality in one of the two alleles of the FVIII gene. We investigated the time
      course of plasma FVIII:C and vWF:Ag levels in 25 obligate carriers of haemophilia
      A after DDAVP infusion. In carriers with a normal FVIII to vWF ratio (> 0.8),
      DDAVP induced a progressive ratio decrease that reached levels significantly
      lower than that taken as cut-off to discriminate between low and normal values
      (0.68 +/- 0.1 vs before 0.912 +/- 0.18). In carriers with a borderline (0.7-0.8)
      or reduced (< 0.7) ratio DDAVP induced a further decrease in the FVIII/vWF ratio,
      albeit with a different kinetic; after an initial increase, values were lower
      than pre-DDAVP figures. In all subjects, following the post-DDAVP peak, plasma
      FVIII progressively decreased while vWF contemporaneously continued to increase.
      In contrast, DDAVP did not induce significant changes in the FVIII/vWF ratio in
      normal females, and the two molecules appeared to increase similarly throughout
      the observation period. These findings indicate that after DDAVP, FVIII increases
      less or for a shorter time than vWF, also in haemophilia A carriers who have a
      normal FVIII/vWF ratio. Hence, DDAVP may help identify haemophilia A carriers,
      especially subjects with normal or borderline ratios. Even though molecular
      biology procedures at present are the best and more reliable tools to identify
      the carrier state, DDAVP seems to improve the accuracy of haemostatic parameters.

PMID- 8874866
TI  - Heparin cofactor II-dependent antithrombin activity of calcium spirulan.
AB  - Calcium spirulan (Ca-SP), a novel sulfated polysaccharide isolated from the blue
      green alga Spirulina platensis, enhanced the antithrombin activity of heparin
      cofactor II (HC II) more than 10000-fold. The apparent second-order rate constant
      of thrombin inhibition by HC II was calculated to be 4.2 x 10(4) M-1 min-1 in the
      absence of Ca-SP, and it increased in the presence of 50 micrograms/ml Ca-SP to
      4.5 x 10(8) M-1 min-1. Ca-SP effectively induced the formation of a thrombin-HC
      II complex in plasma. In the presence of Ca-SP, both the recombinant HC II
      variants Lys173-->Leu and Arg 189-->His, which are defective in interactions with
      heparin and dermatan sulfate, respectively, inhibited thrombin in a manner
      similar to native rHC II. This result indicates that the binding site of HC II
      for Ca-SP is different from the heparin- or dermatan sulfate-binding site. When
      we removed the calcium from the Ca-SP, the compound did not exert any
      antithrombin activity. Furthermore, Na-SP, which was prepared by replacement of
      the calcium in Ca-SP with sodium, accelerated the antithrombin activity of HC II
      as Ca-SP did. We therefore suggest that the molecular conformation maintained by
      Ca or Na is indispensable to the antithrombin activity of Ca-SP. The HC II
      dependent antithrombin activity of Ca-SP was almost totally abolished by
      treatment with chondroitinase AC I, heparinase or heparitinase, but not by
      treatment with chondroitinase ABC and chondroitinase AC II, suggesting that a
      heparin- or dermatan sulfate-like structure is not responsible for the activation
      of HC II by Ca-SP. Ca-SP is therefore thought to be a unique sulfated
      polysaccharide which shows a strong antithrombin effect in an exclusively HC II
      dependent manner.

PMID- 8874867
TI  - Interaction of reteplase with heparin. A comparison between reteplase and
      alteplase.
AB  - Reteplase is a protein consisting of the kringle-2 and protease domains of tissue
      type plasminogen activator (t-PA). Because intravenous heparin will be used as an
      adjunct to thrombolytic therapy with reteplase, we investigated the interactions
      in vitro between heparin and reteplase as well as between heparin and recombinant
      t-PA (alteplase) as a control. Reteplase and alteplase bound completely to a
      heparin-agarose column and eluted respectively at 0.39 M and 0.60 M in a NaCl
      gradient. Two-chain derivatives of reteplase and alteplase eluted at 0.31 M and
      0.52 M NaCl respectively. Plasminogen activation by the two-chain derivatives of
      reteplase and alteplase in a purified system at low ionic strength were
      stimulated by heparin up to 13- and 22-fold, respectively. However, reteplase
      required five times more heparin for maximal stimulation than alteplase. In
      addition, the heparin stimulation of reteplase was more salt sensitive than that
      of alteplase. In conclusion, both heparin binding and heparin stimulation
      experiments showed that heparin interacts with reteplase, but the interaction is
      weaker than with alteplase.

PMID- 8874868
TI  - Haemostatic changes in the pulmonary blood during cardiopulmonary bypass.
AB  - Pulmonary injury may result from the use of cardiopulmonary bypass (CPB). We
      investigated changes in the haemostatic system in the pulmonary vein during CPB
      compared with blood that circulated through the bypass circuit. Paired samples
      were taken from the pulmonary vein and central venous pressure (CVP) line during
      the peri-operative period from ten patients. Plasma levels of factor VII (P <
      0.001), prekallikrein (P < 0.05), antithrombin III (P < 0.001) and heparin
      cofactor II (P < 0.005) were decreased in the pulmonary vein after 20 min of
      bypass compared with pre-operative levels. In the pulmonary vein there was a
      significant increase in neutrophil expressed CD11b (P < 0.001), neutrophil
      elastase: alpha 1-antitrypsin complexes (P < 0.001), endothelin-1(P < 0.001) and
      thrombin-antithrombin complexes (P < 0.001) by the end of bypass compared with
      pre-operative levels. There was no significant change in monocyte expressed
      CD11b, factor XII or C1-esterase inhibitor in the pulmonary vein for the study
      period. None of these variables were significantly different in the pulmonary
      vein compared with CVP line. In the pulmonary vein plasma levels of activated
      factor VII decreased following heparin administration (P < 0.001) in the majority
      of patients which was coincidental to an increase (P < 0.001) in tissue factor
      pathway inhibitor (TFPI). This increase in TFPI was significantly higher in the
      pulmonary vein compared with CVP line (P < 0.05) There was a decrease in
      neutrophil count by 20 min on CPB in both the pulmonary vein and CVP line (P <
      0.001) and this did not return to pre-operative levels in the pulmonary vein.
      Soluble thrombomodulin levels decreased by 20 min on CPB in the CVP line (P <
      0.05) but tended to increase in the pulmonary vein, although this was not
      statistically significant. In conclusion we found evidence of thrombin generation
      and possible endothelial damage together with increased neutrophil activation and
      adhesion molecule expression in the pulmonary vein during CPB which may play an
      important role in the development of post-CPB pulmonary injury.

PMID- 8874869
TI  - A novel nonsense mutation in the antithrombin III gene (Cys-4-->stop) causing
      recurrent venous thrombosis.
AB  - We describe a novel mutation identified in the antithrombin III (AT-III)
      propeptide responsible for AT-III deficiency. This mutation, a C to A
      transversion in exon 2, converts the cysteine at position -4 into a stop codon
      (TGC-->TGA). In this family with severe thrombophilia, the mutation co-segregates
      with the clinical phenotype.

PMID- 8874870
TI  - Laboratory studies on the reliability of a commercial immunoassay for thrombin
      antithrombin complexes.

PMID- 8874871
TI  - Behaviour of the transgenic (mREN2)27 rat.
AB  - The first model of genetically engineered hypertension, the transgenic rat TGR
      (mREN2)27, provides a unique opportunity to study the behavioural effects of an
      altered brain renin-angiotensin system. The TGR (mREN2)27 rats, characterised by
      fulminant hypertension, show differences in both the peripheral and central
      angiotensin systems. The behaviour of male transgenic TGR (mREN2)27 and male
      Sprague-Dawley rats were determined by 4 behavioural tests. While on the elevated
      X-maze the TGR (mREN2)27 rat showed a greater 'anxiogenic' profile (fewer open
      arm entries) than the control Sprague-Dawley rats, this 'anxiogenic' profile
      increased further during a second exposure to the elevated X-maze 24 h later. In
      comparison the behaviour of the male Sprague-Dawley rats was not different
      between the two exposures to the elevated X-maze. Locomotor activity did not
      differ between either the TGR (mREN2)27 or Sprague-Dawley rats when placed in a 1
      m2 open-field for 10 min. A short period of fluid-deprivation (3 h) reversed the
      'anxiogenic' profile of the TGR (mREN2)27 on the elevated X-maze. Administration
      of captopril (20 mg . kg-1 body weight) in the drinking water of the TGR
      (mREN2)27 rats and Sprague-Dawley rats reversed the anxiogenic profile of the TGR
      (mREN2)27 rat on the elevated X-maze but did not alter the behaviour of the
      Sprague-Dawley rats.

PMID- 8874872
TI  - Opiate withdrawal increases ProTRH gene expression in the ventrolateral column of
      the midbrain periaqueductal gray.
AB  - The midbrain periaqueductal gray matter (PAG) has a critical role in the
      modulation of behavioral and autonomic manifestations of the opiate withdrawal
      syndrome. We report a nearly 5-fold increase in proTRH gene expression in neurons
      of the ventrolateral column of the PAG following naltrexone precipitated morphine
      withdrawal. The accumulation of immunoreactive proTRH-derived peptides, but not
      the mature TRH tripeptide was concomitantly observed in these cells. These
      findings indicate that proTRH-derived peptides synthesized in neurons of the
      ventrolateral PAG may function as modifiers of opiate withdrawal responses.

PMID- 8874873
TI  - Sexual motivation: involvement of endogenous opioids in the ventral tegmental
      area.
AB  - The sexual motivation and performance of male rats were observed in a bilevel
      testing chamber after bilateral infusion of 40 pmol beta-endorphin, 2.75 nmol
      naloxone or saline into the ventral tegmental area for four succeeding, weekly
      tests. In the 5 min prior to introduction of the female rat, the male rat
      explores the bilevel testing chamber. It was previously shown that the increase
      over tests of these anticipatory level changes is sexually motivated and a
      response to olfactory stimuli. Naloxone infusion into the VTA prevented the
      increase of anticipatory level changes. beta-Endorphin failed to affect the
      anticipatory level-changing behavior. The sexual performance was unaffected by
      naloxone or beta-endorphin treatment, but the number of ejaculating rats
      decreased with repeated testing after naloxone treatment. It is concluded that
      endogenous opioid systems in the ventral tegmental area contribute to the
      stimulation of sexual motivation and/or reward, presumably by stimulating the
      mesolimbic dopamine system in response to sex-related olfactory stimuli.

PMID- 8874874
TI  - Concurrent androgenic stimulation of the ventral tegmental area and medial
      preoptic area: synergistic effects on male-typical reproductive behaviors in
      house mice.
AB  - Cannulae containing testosterone proprionate (T) were bilaterally implanted into
      the medial preoptic area (MPO), the ventral tegmental area (VTA), or both areas
      concurrently (MPO/VTA) of castrated male house mice. A fourth group of castrates
      in which the intracranial implants missed their targets (MIMP) served as
      controls. In addition, other castrates were implanted subcutaneously with empty
      silastic capsules (BSIL) or silastic capsules containing T (TSIL). All subjects
      were examined for the following male-typical behaviors: mounting, attraction to
      female urine, ultrasonic mating vocalizations and urinary scent marking. In
      addition, the males were tested for activity levels to insure that they were not
      motorically impaired. In general, TSIL implants restored all male-typical
      behaviors to normal levels, whereas BSIL and MIMP implants were generally
      ineffective. Similar to previous findings, MPO implants alone completely restored
      ultrasonic vocalizations, partially restored urine marking, and had little or no
      effect upon mounting or urine preference. In contrast, VTA implants alone were
      ineffective at restoring any of these male-typical behaviors. However, the
      combined MPO/VTA implants were the most effective in restoring male-typical
      behaviors. In fact, a synergism between concurrent hormone action in the MPO and
      VTA was seen for mounting and urine preference. We interpret these data to
      indicate that androgen may act simultaneously in the MPO and VTA for more
      complete expression of some male-typical reproductive behaviors.

PMID- 8874875
TI  - Parvalbumin in the human anterior cingulate cortex: morphological heterogeneity
      of inhibitory interneurons.
AB  - The calcium-binding protein parvalbumin (PV) is a marker for a certain subset of
      GABAergic cortical interneurons. In the present study, indirect
      immunocytochemistry with an antibody against PV was performed on serial sections
      of human anterior cingulate cortex (Brodmann's area 24), an important relay
      centre of the limbic system. PV-positive structures are distributed in a layer-
      and cell type-specific manner. Based on morphological features and laminar
      distribution pattern, PV-immunoreactive interneurons are subdivided into eight
      different classes. PV immunoreactivity within the neuropil comprises dendritic
      and axonal processes. Area 24 contains two densely immunolabelled neuropil bands
      in layers III and Vb. Axon cartridges are preferably located in layers V and VI.
      The results provide a "PV immunoarchitecture' as a basis for further studies of
      PV immunoreactivity under pathological conditions. PV is assumed to play a role
      in maintaining calcium homeostasis in nerve cells, and to modulate neuronal
      excitability and resistance to biochemical damage. On the other hand, PV
      immunoreactivity has recently been shown to undergo characteristic changes during
      different stages of brain maturation. Therefore, examination of PV-positive
      structures will provide new insights into cortical circuitry in neurodegenerative
      as well as neurodevelopmental disorders.

PMID- 8874876
TI  - Relationship between cholinergic dysfunction and discrimination learning
      disabilities in Wistar rats following chronic cerebral hypoperfusion.
AB  - The effects of chronic hypoperfusion of cerebral blood flow (CBF) on central
      cholinergic indices and intellectual functions were investigated in rats. Male
      Wistar rats, aged 9 weeks, were anesthetized with pentobarbital, and the
      bilateral common carotid arteries were permanently ligated. Cortical CBF in the
      hypoperfused rats was markedly decreased at 6 weeks after the operation. In the
      hypoperfused group, cholinergic indices were changed to consist two phases after
      the operation, before (acute) and after (chronic) 6 weeks after the operation. At
      6 weeks, choline acetyltransferase activity was restored to the sham-operated
      level compared with the changes in the frontal cortex and thalamus + midbrain at
      3 weeks. On the other band, the maximum number of muscarinic acetylcholine
      receptors was reduced in the frontal cortex, hippocampus and striatum at 6 weeks
      and thereafter remained at this low level. In discrimination learning task, the
      percentage of correct responses in the hypoperfused rats was generally reduced in
      contrast with that of the sham-operated rats, although the number of total
      responses were not changed. As a consequence, cholinergic dysfunctions correlate
      with discrimination learning disabilities in the hypoperfused rats. These
      findings suggest that the hypoperfused rat may be useful for the cerebrovascular
      type dementia model to clarify pathophysiology.

PMID- 8874877
TI  - Effect of cerebral hypoxia on NMDA receptor binding characteristics after
      treatment with 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) in
      newborn piglets.
AB  - Previous studies have shown that hypoxia modifies the NMDA receptor/ion channel
      complex in cortical brain cell membranes of newborn piglets. The present study
      tests the hypothesis that blockade of the glutamate recognition site of the NMDA
      receptor with the competitive antagonist 3-(2-carboxypiperazin-4-yl)propyl-1
      phosphonic acid (CPP) prevents modification of the receptor during hypoxia.
      Twenty seven anesthetized, ventilated newborn piglets were randomized into four
      groups: 7 normoxic (Nx), 6 CPP-treated normoxic (CPP-Nx), 8 hypoxic (Hx) and 6
      CPP-treated hypoxic (CPP-Hx). Treatment groups received CPP 2 mg/kg i.v. The CPP
      Hx group received CPP 30 min prior to hypoxia, which was induced by lowering the
      FiO2 to 5-7% for 1 h. Physiologic data showed no change in heart rate, blood
      pressure, arterial blood gas values, glucose or lactate following CPP
      administration. During hypoxia there was a significant decrease in PaO2, pH and
      an increase in lactate compared to baseline values. The CPP-Hx group had
      significantly higher lactate levels than the Hx group during hypoxia. P2 membrane
      fractions were prepared and thoroughly washed. Characteristics of the NMDA
      receptor ion channel were determined by [3H]MK-801 binding assays and
      characteristics of the glutamate recognition site by specific NMDA-displaceable
      [3H]glutamate binding assays. Brain tissue ATP and PCr levels confirmed tissue
      hypoxia, and were not preserved by CPP administration. [3H]MK-801 binding assays
      revealed that CPP treatment attenuated the hypoxia-induced decrease in the number
      of receptors (Bmax) and receptor binding affinity (Kd) during hypoxia. CPP
      treatment also decreased receptor affinity (increased Kd) for [3H]MK-801 binding
      during normoxia and hypoxia. Assays of [3H]glutamate binding revealed that
      hypoxia decreased both the Bmax and the Kd of the NMDA receptor for [3H]glutamate
      and both were preserved by CPP treatment prior to hypoxia. CPP had no effect on
      [3H]glutamate Bmax or Kd during normoxia. We conclude that hypoxia decreases the
      Bmax and Kd of the NMDA receptor glutamate recognition site for [3H]glutamate and
      the ion channel site for [3H]MK-801 in newborn piglets. These changes are
      prevented by CPP administration prior to hypoxia. The different effects of CPP
      binding during normoxia and hypoxia suggest a use-dependent mechanism for CPP
      binding during hypoxia, possibly through an hypoxia-induced alteration of the
      high-affinity binding site for CPP. During both normoxia and hypoxia CPP binding
      appeared to induce a conformational change in the receptor causing a decrease in
      binding affinity for [3H]MK-801. CPP administration did not preserve brain tissue
      ATP or PCr levels during hypoxia and may alter cellular metabolism in addition to
      its action at the NMDA receptor. However, even with depletion of the energy
      precursors ATP and PCr, and with higher lactate levels in the CPP-Hx group, CPP
      was able to maintain NMDA receptor binding characteristics during hypoxia and may
      decrease excitotoxic cellular damage from hypoxia.

PMID- 8874878
TI  - The effect of central administration of prolactin on food intake in virgin female
      rats is dose-dependent, occurs in the absence of ovarian hormones and the latency
      to onset varies with feeding regimen.
AB  - Lactation in mammals is characterized by a marked hyperphagia and significantly
      elevated levels of prolactin (PRL). Several recent experiments in our laboratory
      have provided evidence for a causal relationship between PRL and hyperphagia. The
      present series of studies revealed that PRL injected intracerebroventricularly
      (i.c.v.) twice daily for ten days to free feeding virgin female rats produced a
      dose-dependent increase in food intake without disrupting vaginal cyclicity, that
      the hyperphagic effect of centrally administered PRL was not dependent on the
      presence of ovarian hormones, that it did not selectively potentiate feeding
      during the light or dark phase of the daily light cycle and that the latency of
      the feeding response to i.c.v. PRL administration was shorter in food restricted
      animals. Taken together, these results support the idea that PRL acts centrally
      to potentiate food intake.

PMID- 8874879
TI  - Neurocalcin immunoreactivity in the rat accessory olfactory bulb.
AB  - The distribution and morphology of neurocalcin-immunopositive neurons have been
      studied in the rat accessory olfactory bulb. Different subsets of neurons
      displaying neurocalcin immunoreactivity were found in the glomerular layer, the
      external plexiform layer and the internal plexiform layer. The most abundant
      staining was detected in the glomerular layer where neurocalcin-immunoreactive
      periglomerular cells and external tufted cells were observed in the lateral
      glomeruli, whereas the central region of this layer was practically devoid of
      immunopositive neurons. In the external plexiform layer, medial tufted cells and
      Van Gehuchten cells displayed neurocalcin immunoreactivity. In the internal
      plexiform layer, interneurons classified as horizontal cells and vertical cells
      of Cajal were neurocalcin-immunoreactivity. In the internal plexiform layer,
      interneurons classified as horizontal cells and vertical cells of Cajal were
      neurocalcin-immunostained. The staining pattern for neurocalcin in the accessory
      olfactory bulb showed similarities with the immunostaining described in this
      brain region for another EF-hand calcium binding protein, calbindin D-28k.
      However, after double immunohistochemical labeling, colocalization of both
      proteins in the same neuron was not observed, reflecting a biochemical
      heterogeneity within morphologically homogeneous neuronal groups.

PMID- 8874880
TI  - Histological and functional evaluation of experimental spinal cord injury:
      evidence of a stepwise response to graded compression.
AB  - Most experimental spinal cord injury studies described to date have relied on a
      limited number of injury gradations, and have tacitly assumed that outcome
      (functional, histological, and/or neurophysiological) is a monotonically graded
      function of injury severity. In contrast, the present study provides evidence
      that functional and morphological outcome after spinal cord compression injury
      may occur in a discontinuous, non-graded manner in response to linearly graded
      injury levels. The thoracic spinal cord of adult rats was transiently compressed
      to thicknesses from 1.8 to 0.8 mm in 0.2 mm steps, or sham injury was
      administered. Open field motor behavior and segmental reflexes were evaluated up
      to 21 days post injury and correlated with histological measures and injury
      level. The highest correlation was between histological outcome and open field
      motor scores. Among the six injury groups, only three significantly different
      outcomes were apparent in the open field, reflex, and histological measures,
      consisting of the injury group pairs 1.8/1.6, 1.4/1.2, and 1.0/0.8 mm. At day 21,
      the 1.8/1.6 mm injury groups were also indistinguishable from the sham injury
      group. The implications of these findings in terms of therapeutic studies are
      discussed. Comparison of the temporal outcome patterns among contusion and
      compression injuries in rats and other species also revealed a significant
      species difference: a period of delayed or secondary functional loss reported in
      the guinea pig was not present in the rat.

PMID- 8874881
TI  - Protein tyrosine kinase inhibitors suppress the production of nitric oxide in
      mixed glia, microglia-enriched or astrocyte-enriched cultures.
AB  - Nitric oxide (NO) produced by glial cells has been implicated in the
      neuropathogenesis of various diseases. However, the signaling transduction
      pathway(s) for the production of NO in these cells is not well understood. To
      test whether protein tyrosine kinases (PTKs) are required for signaling events of
      NO production in glial cells, this study examined the effects of genistein and
      tyrphostin A25, two potent inhibitors of PTKs, on the production of NO in mouse
      primary mixed glia, microglia-enriched or astrocyte-enriched cultures exposed to
      lipopolysaccharide (LPS) or a combination of LPS and interferon-gamma (IFN
      gamma). LPS induced a dose-dependent increase in NO production from the mixed
      glia cultures. The LPS-induced NO production was significantly enhanced by
      stimulating the cells with IFN gamma. Genistein or tyrphostin A25 inhibited the
      production of NO in both LPS- and IFN gamma/LPS-stimulated mixed glia cultures.
      The production of NO in the stimulated microglia-enriched or astrocyte-enriched
      cultures was also inhibited by tyrphostin A25. To verify the cellular sources of
      NO, immunocytochemical staining of inducible NO synthase (iNOS) was followed by
      staining with the microglia marker Mac-1 or the astrocyte marker glial fibrillary
      acid protein (GFAP) in microglia-enriched or astrocyte-enriched cultures. The
      expression of iNOS and the production of NO in microglia-enriched cultures were
      significantly higher than those in the identically stimulated astrocyte-enriched
      cultures. These results demonstrate that PTKs are involved in the signaling
      events of LPS-induced NO production in microglia and astrocytes, and that
      microglia are more responsive than astrocytes to stimuli which induce NO. These
      results may provide insights into therapeutic interventions in the pathway for NO
      production in the brain.

PMID- 8874883
TI  - A retrograde fluorescent-labeling study of direct relationship between the limbic
      (anterodorsal and anteroventral thalamic nuclei) and the visual system in the
      albino rat.
AB  - Injecting different fluorescent tracers into the right anterodorsal
      (AD)/anteroventral (AV) or AD/AV and the primary visual nuclei of dorsal lateral
      geniculate (dLGN) or superior colliculus (SC), a direct projection from the left
      retina to these anterior thalamic nuclei was ascertained in the central part of
      ventro-nasal retinal quadrant. Single-labeled cells were of small type. No double
      labeled cells were demonstrated.

PMID- 8874882
TI  - Opposite strain-dependent effects of post-training corticosterone in a passive
      avoidance task in mice: role of dopamine.
AB  - Post-training administration of corticosterone (0.1-1 mg/kg) dose-dependently
      improves retention of an inhibitory avoidance response in C57BL/6 mice, whilst
      impairing it in the DBA/2 strain. The effects on retention performance induced by
      the hormone in C57BL/6 and DBA/2 mice appear to be due to an effect on memory
      consolidation. In fact, they were observed when the drug was given at short, but
      not long, periods of time after training, i.e., when the memory trace is
      susceptible to modulation. In the absence of pharmacological manipulations, the
      two strains showed a significant increase of plasma corticosterone levels 15 min
      after passive avoidance training that disappeared within 30 min, and similar step
      through latencies on the test day. However, although no strain differences were
      observed for sensitivity to shock thresholds, the increase in plasma
      corticosterone levels elicited by passive avoidance training was more pronounced
      in mice of the DBA/2 strain (+160%) than in C57BL/6 mice (+52%). Moreover, DBA/2
      mice were characterised by a higher number of either Type I or Type II
      corticosteroid receptors in the hippocampus in comparison with C57BL/6 mice.
      Finally, the strain-dependent effects of an intermediate dose of corticosterone
      were enhanced by pretreatment with either the selective D1 or D2 dopamine (DA)
      receptor agonists SKF 38393 and LY 171555 and reversed by pretreatment with
      either selective D1 or D2 DA receptor antagonists SCH 23390 and (-)-sulpiride
      administered at per se non-effective doses. The present results indicate that
      studies in inbred strains of mice can dissect opposite effects of corticosterone
      on memory consolidation possibly due to its action at different steps or
      components of the multiphasic pathway of memory consolidation. Moreover, they
      suggest that some of these steps involve an interaction between the hormone and
      brain DA system.

PMID- 8874884
TI  - The neurotensin receptor antagonist SR 48692 decreases extracellular striatal
      GABA in rats.
AB  - Intracranial microdialysis was utilized to assess the effects of the novel
      neurotensin antagonist SR 48692 on extracellular gamma-amino-butyric acid (GABA)
      and glycine in the striatum. Subcutaneous injection of SR 48692 (0.2 mg/kg)
      significantly decreased extracellular striatal GABA levels, with peak decreases
      occurring 2-3 h post-injection. Injection of SR 48692 had no significant effect
      on glycine levels. These data suggest that endogenous neurotensin may modulate
      striatal GABA levels.

PMID- 8874885
TI  - Effects of exercise and fetal spinal cord implants on the H-reflex in chronically
      spinalized adult rats.
AB  - This study investigated the modulation of hindlimb reflex excitability after
      transection of the spinal cord in adult rats. After transection, the H-reflex
      exhibited decreased depression at high stimulation frequencies compared to intact
      animals. Groups of animals which received a spinal cord transection followed by
      either an exercise regimen for the hindlimbs or a fetal spinal cord implant,
      showed high stimulation frequency depression similar to controls. This suggests
      that each of these palliative strategies helped to "normalize' the excitability
      of specific spinal reflexes.

PMID- 8874886
TI  - Brain somatostatin depletion by cysteamine attenuates the penile erection induced
      by serotonergic and dopaminergic, but not by cholinergic, activation in rats.
AB  - To clarify the role of brain somatostatin in the expression of penile erection,
      the effects of cysteamine, a somatostatin depletor, on the penile erection
      induced by serotonergic, cholinergic and dopaminergic stimulants were
      investigated in rats. Fenfluramine (0.1-10 mg/kg, i.p.), pilocarpine (0.032-3.2
      mg/kg, i.p.) and apomorphine (0.01-1 mg/kg, i.p.) induced penile erection in
      rats, with bell-shaped dose-response curves. Pretreatment with cysteamine (200
      mg/kg, s.c.) significantly attenuated the penile erection induced by fenfluramine
      and apomorphine, but scarcely affected that induced by pilocarpine. Neurochemical
      measures revealed that cysteamine pretreatment significantly reduced the
      somatostatin content in all brain regions examined. These results provide the
      first pharmacological evidence that the brain somatostatin may play an important
      role in drug-induced penile erection.

PMID- 8874887
TI  - Occurrence of axons with certain immunohistochemical markers in teleost gingiva
      and teeth.
AB  - The occurrence of axons with certain neurochemical markers in gingiva and teeth
      in the lower jaw of the cichlid Tilapia mariae was examined by
      immunohistochemistry. It was found that gingival and pulpal axons can be labelled
      with antibodies against calcitonin gene-related peptide, substance P, tyrosine
      hydoxylase, neuropeptide Y, choline acetyl transferase and vasoactive intestinal
      polypeptide. It is concluded that both gingival and dental domains in T. mariae
      contain axons with sensory and autonomic chemical phenotypes, the occurrence and
      distribution of which are generally similar to the mammalian counterpart.

PMID- 8874888
TI  - Calcineurin inhibitors, FK506 and cyclosporin A, suppress the NMDA receptor
      mediated potentials and LTP, but not depotentiation in the rat hippocampus.
AB  - The effects of FK506, a Ca2+/calmodulin-dependent phosphatase 2B (calcineurin)
      inhibitor, on the NMDA receptor-mediated potentials and synaptic plasticity were
      investigated in the CA1 region of the rat hippocampus. Bath application of FK506
      (50 microM) produced a 45% inhibition on the NMDA receptor-mediated potentials.
      FK506 also inhibited the induction of long-term potentiation (LTP), but had no
      effect on the depotentiation in the CA1 hippocampus. Cyclosporin A (100 microM),
      another calcineurin inhibitor, mimicked the effects of FK506 on the NMDA
      responses and synaptic plasticity. These results suggest that FK506 inhibits the
      activity of NMDA receptors via the involvement of calcineurin. The differential
      effects of FK506 on LTP and depotentiation may attribute to the partial
      inhibition on the activity of NMDA receptors and the subsequent attenuation of
      intracellular Ca2+ increase.

PMID- 8874889
TI  - Decrease of (+)-3-[125I]MK-801 binding to NMDA brain receptors revealed at
      puberty in rats treated neonatally with monosodium glutamate.
AB  - Obesity, altered pattern of gonadal hormone secretion, advanced vaginal opening,
      irregular cycling, altered sexual behavior and infertility are the effects of the
      neonatal administration of monosodium glutamate (MSG) to rodents. These are the
      consequences of lesions located mainly in the hypothalamic region. It is believed
      that the receptors to N-methyl-D-aspartic acid (NMDA) actively participate in the
      onset and development of such lesions, on the other hand, they may be altered by
      neuronal dysfunction as well, seriously compromising the glutamatergic pathways
      that are involved in the neuroendocrine regulation. To clarify the scope of the
      lesion induced by MSG and its probable effects on the NMDA receptors, we measured
      them with a very sensitive ligand for autoradiography, (+)-3-[125I]MK-801.
      Coronal cuts at the level of the arcuate-median eminence of brains from 4-, 8-
      and 40-day-old rats treated neonatally with MSG (4 mg/g) or saline (controls)
      were examined. In the normal hypothalamus, NMDA receptor labelling was higher in
      the young animals than in the 40-day-old animals, and this was observed in both
      control and treated rats. NMDA receptor labelling of rats at puberty was very
      low, and no apparent differences were observed between groups. In contrast, in
      areas where an increase in NMDA binding sites normally occurs with development, a
      significant impairment of the normal augmentation of MK-801 binding was revealed.
      In the hippocampal layers, stratum radiatum and stratum oriens and in the
      cerebral cortex of 40-day-old rats treated with MSG a lower amount of binding was
      observed, of about 50% fewer sites compared to the untreated controls at the
      level of CA3 and in the outer layer of the parietal cortex. These results suggest
      that at an early stage of the MSG lesion the NMDA receptors located in the
      hypothalamus and other brain areas are apparently expressed normally, but at
      puberty the effects of the lesion are revealed in the hippocampus and cerebral
      cortex by a decrease in the density of binding. Thus, the abnormal neuroendocrine
      and behavioral responses displayed by the MSG-treated rats may be contributed
      partially by the alteration of the NMDA receptors in these areas.

PMID- 8874890
TI  - The prepubertal ontogeny of luteinizing hormone releasing hormone-like
      immunoreactivity in the diencephalon and telencephalon of the male Meishan pig
      brain.
AB  - Luteinizing hormone releasing hormone (LHRH) is a decapeptide that regulates
      reproductive function and behaviors in mammalian species. Because of the
      importance of proper reproductive function and efficiency in agricultural
      species, we have investigated the prepubertal ontogeny of LHRH-like
      immunoreactivity (IR) in the male Meishan pig. The Meishan is a Chinese breed
      known for reproductive traits including increased litter size and precocious
      puberty, but slow growth and obesity. Brains of animals from gestational day (g)
      30, 50, 70, 90 and 110 and postnatal day (pn) 1, 10, 20 and 50 (duration of
      pregnancy averaged 114 days) were processed using a standard immunohistochemical
      technique utilizing a commercially available rabbit anti-LHRH antibody. LHRH-IR
      in cell bodies and fibers was detected at g30 entering the brain via the terminal
      nerve and in the septal region of the basal telencephalon. The number of
      immunoreactive cells increased at g50 and cells were localized primarily to the
      septum, organum vasculosum of the lamina terminalis, preoptic area and lateral
      hypothalamus, whereas immunoreactive fibers were present throughout the septum
      and hypothalamus and had reached the median eminence. The density and
      distribution of immunoreactive fibers increased by g70 and g90, but did not
      change dramatically from g90 to pn50. These results indicate that LHRH may be
      present in the Meishan brain earlier during development and fibers containing
      LHRH-IR appear to reach the median eminence earlier than previously reported for
      the domestic pig. These results suggest a breed difference in the ontogeny of
      reproductive control systems in the pig. Future studies utilizing direct
      comparisons between domestic and Chinese breeds will be required to investigate
      the apparent differences in the ontogeny of LHRH-containing systems in the pig.

PMID- 8874892
TI  - Delayed neurogenesis in the albino retina: evidence of a role for melanin in
      regulating the pace of cell generation.
AB  - Melanin or an associated product in the retinal pigment epithelium (RPE)
      regulates retinal maturation, because in albino mammals the central retina is
      underdeveloped and there is a cell specific deficit in the rod population.
      Further, retinal projections through the chiasm are disrupted systematically.
      Here we test the hypothesis that melanin influences the birth dates of cells in
      the ganglion cell layer of the rat. [3H]Thymidine was injected at stages between
      E12 and E21 into mothers carrying both pigmented and albino fetuses. The animals
      were examined at maturity. Both pigmentation genotypes showed a centre to
      periphery pattern of cell production. Injections at E12 resulted in similar
      patterns of labelling in central regions. But from E14 labelled cells in the
      albinos were consistently closer to the central retina than those in their
      pigmented litter mates, suggesting a temporal lag in the centre to periphery
      pattern of cell production. By E21 there was little or no label in the pigmented
      animals, but it persisted in albinos, being similar in distribution to that in
      pigmented animals injected at E19. These results are consistent with the notion
      that melanin, or more likely an affiliated agent, in the RPE plays a role in
      regulating mitosis in the neural retina, possibly by influencing an aspect of the
      cell cycle. This may be the origin of the abnormalities found in the adult.

PMID- 8874891
TI  - Phenytoin pretreatment prevents hypoxic-ischemic brain damage in neonatal rats.
AB  - This study was performed to investigate whether the anticonvulsant phenytoin has
      neuroprotective effect in a model of hypoxia-ischemia with neonatal rats. The
      left carotid artery of each rat was ligated, followed by 3 h of hypoxic exposure
      (8% O2) in a temperature-regulated environment (36 degrees C). Two weeks later,
      brain damage was assessed by measuring loss of brain hemisphere weight. Phenytoin
      had no effect on body temperature or plasma glucose, but attenuated brain damage
      in a dose-dependent manner (3, 10, and 30 mg/kg i.p.) when administered before
      the hypoxic episode. Phenytoin administered during or after hypoxia did not alter
      hypoxic brain damage significantly. A parallel experiment using histological
      examination of frozen brain sections demonstrated less brain infarction after
      phenytoin treatment (30 mg/kg i.p.). In an additional experiment measuring
      breakdown of an endogenous brain calpain substrate, spectrin, phenytoin treatment
      reduced this measure of early cellular damage. Our results indicate that
      pretreatment with phenytoin is neuroprotective at a plasma phenytoin
      concentration of approximately 12 micrograms/ml. These results are consistent
      with the hypothesis that blockade of voltage-dependent sodium channels reduces
      brain damage following ischemia.

PMID- 8874893
TI  - Reinnervation of stratum lucidum by hippocampal mossy fibers is developmentally
      regulated.
AB  - Mossy fibers from dentate gyrus granule cells establish synapses on CA3 pyramidal
      neurons during the first 3 postnatal weeks in the rat. Mossy fiber synapses are
      primarily restricted to the stratum lucidum. When examined by Timm stain after 10
      14 days in vitro, cultured hippocampal slices from postnatal day 4 rat pups show
      a similar mossy fiber termination pattern in stratum lucidum. Thus, axon guidance
      cues used by mossy fibers in vivo appear to be preserved in these cultured
      slices. Three experimental manipulations were performed on hippocampal slice
      cultures to examine whether the axon guidance cues used by mossy fibers are
      developmentally regulated. First, mossy fibers were transected on the day of
      culture or day 7 in vitro. Mossy fibers transected on either day were able to
      reestablish their synaptic pattern in stratum lucidum of CA3. Second, dentates
      and hippocampi of same age or different age were co-cultured. Same age co
      cultures (P4 dentates to P4 hippocampi or P11 dentates to P11 hippocampi) showed
      good mossy fiber reinnervation of stratum lucidum, as did different age co
      cultures from P4 dentates to P11 hippocampi. However, P11 dentates to P4
      hippocampi co-cultures showed little mossy fiber reinnervation of stratum
      lucidum. Third, new P4 or P11 dentates were co-cultured onto hippocampal slices
      in which mossy fibers had been allowed to degenerate. New mossy fibers
      reinnervated these hippocampi, but did not reestablish their normal synaptic
      pattern in stratum lucidum. These three experimental manipulations suggest that
      mossy fiber axon guidance mechanisms are developmentally regulated, and that
      existing mossy fibers play a role in directing mossy fiber reinnervation of
      stratum lucidum.

PMID- 8874894
TI  - Distribution of FMRFamide-like immunoreactivity in the brain and pituitary of
      Rana esculenta during development.
AB  - Developmental aspects of the distribution of FMRFamide (Phe-Met-Arg-Phe-NH2)
      immunoreactivity (ir) were investigated by indirect immunofluorescence in the
      brain, pituitary and terminal nerve of the frog, Rana esculenta. Soon after
      hatching. FMRFamide neurons were found in the proximal terminal nerve, mediobasal
      olfactory bulb, caudal dorsolateral pallium, diagonal band of Broca, anterior
      preoptic area, suprachiasmatic area, thalamus, infundibulum, and developing
      pituitary. FMRFamide fibers were present in the olfactory epithelium, terminal
      nerve, olfactory bulbs, dorsal and midventral telencephalon, epiphysis,
      mediolateral thalamus, pretectal gray, optic tectum, infundibulum, posterior
      interpeduncular nucleus-tegmentum area, and rostral rhombencephalon. During
      successive developmental stages, ir neurons were no longer observed in the dorsal
      telencephalon and pituitary. In late larval stages, ir neurons appeared in the
      medial septal area, and ir fibers in the cerebellum and torus semicircularis. At
      the same time, the frequency of ir neurons increased progressively in the
      anterior preoptic area, suprachiasmatic area and infundibulum. FMRFamide-ir
      neurons were never revealed in mesencephalon and rhombencephalon. Numerous ir
      fibers terminated in the median eminence and intermediate lobe of the pituitary.
      The adult pattern of distribution of FMRFamide-ir elements in the brain was
      achieved during the postmetamorphic development. In light of the existing
      literature, the possible placodal origin of forebrain-located FMRFamide neurons
      is briefly discussed.

PMID- 8874895
TI  - Neurogenesis of cholinoceptive neurons in the chick retina.
AB  - Immunocytochemistry and [3H]thymidine autoradiography were combined in this study
      to determine the neurogenesis of cholinoceptive cells in the chick retina. After
      injections of [3H]thymidine between embryonic days 1 and 11, the time of birth of
      retinal neurons containing either the alpha 3 or the alpha 8 subunit of the
      nicotinic acetylcholine receptors was determined. The results indicate that the
      alpha 3-positive neurons in the ganglion cell layer leave the cell cycle from E2
      through E7, and those in the inner nuclear layer (amacrine and displaced ganglion
      cells) from E2 through E9. The alpha 8-positive cells in the ganglion cell layer
      were born from E1 through E7, and those in the inner nuclear layer (amacrine and
      bipolar cells) from E2 through E11. These data suggest that the time of birth of
      cholinoceptive neurons in the chick retina follows the general pattern of cell
      generation in the chick retina, and that alpha 8-positive cells in the ganglion
      cell layer start to leave the cell cycle almost one day earlier than the alpha 3
      positive cells in the same layer.

PMID- 8874896
TI  - Olivocochlear innervation of inner and outer hair cells during postnatal
      maturation: an immunocytochemical study.
AB  - Changes in the expression of several neurochemical markers associated with either
      axonal growth (GAP-43), synaptic vesicles (synaptophysin), or the cholinergic
      population of lateral olivocochlear (OC) efferents were investigated in the
      postnatal cochlea of hamsters. Growth-associated protein was expressed in the
      neonatal cochlea but not in the adult; immunoreactivity was found below inner
      hair cells (IHCs) from postnatal day (P) 2 through P14 and below outer hair cells
      (OHCs) from P5 to P14. In contrast, synaptophysin was expressed in both the
      neonate and adult cochlea; immunoreactivity was found below IHCs around P4 and
      below OHCs at P5. Both GAP-43 and synaptophysin immunoreactivities occurred first
      below IHCs in basal regions of the cochlea. Efferent fibers containing calcitonin
      gene-related peptide (CGRP) immunoreactivity were identified as early as P4
      within the cochlear nerve but were not observed underneath IHCs until P7. Similar
      to GAP-43 and synaptophysin immunoreactivity, CGRP expression followed a basal to
      apical gradient; however, expression below OHCs appeared restricted to apical
      regions. These data raise the possibility that efferents expressing growth
      proteins and efferents expressing synaptic vesicle proteins co-exist during the
      first postnatal week. Furthermore, it is hypothesized that CGRP-containing
      lateral OC neurons form part of a later, secondary innervation to the cochlea.

PMID- 8874897
TI  - Entactin immunoreactivity in immature and adult rat brain.
AB  - Entactin (nidogen) is a glycoprotein of 150 kDa mainly found in the basement
      membranes of peripheral tissues where it is co-localized and forms a very tight
      complex with the outgrowth-promoting molecule laminin. In the present report we
      tested by immunoblotting the specificity of polyclonal antibodies to laminin and
      entactin isolated from Engelbreth-Holm-Swarm (EHS) mouse sarcoma and investigated
      laminin and entactin immunoreactivities in the hippocampus of newborn, adult
      control and kainate-injured rats. The three polyclonal antibodies to laminin (two
      of them commercial) used in the present study stained somas of neurons, blood
      vessels and reactive glial cells, in agreement with previous reports.
      Nevertheless, all of them cross-reacted with entactin. The anti-entactin serum,
      which specifically recognized entactin protein, but not laminin or fibronectin,
      stained mainly the walls of blood vessels in rat brain slices. We observed a
      stronger entactin expression in immature than in adult brain, and a dramatic
      increase of vascular staining in kainate-injured hippocampus, suggesting a
      contribution of entactin to both development and reactive angiogenesis.

PMID- 8874898
TI  - Migration of GnRH-immunoreactive neurons from the olfactory placode to the brain:
      a study using avian embryonic chimeras.
AB  - Previous studies suggest that gonadotropin-releasing hormone (GnRH) neurons
      appear in the olfactory placode and subsequently migrate into the brain during
      embryonic development. The aim of the present study was to obtain direct evidence
      for migration of GnRH neurons from the olfactory placode into the brain.
      Olfactory placodes from quail embryos were transplanted isotopically and
      isochronically, to replace the unilaterally ablated olfactory placodes of chick
      embryos. The chimeric embryos were allowed to develop for several days until they
      reached the embryonic stages when GnRH neurons are seen in the brain in normal
      embryos. Quail olfactory epithelia were formed in the host chick embryos. Quail
      olfactory nerves were also formed and reached the olfactory bulb or primordial
      olfactory bulb. GnRH-immunoreactive cells of quail origin revealed by a triple
      staining method were observed in the quail olfactory epithelium, quail olfactory
      nerve, chick olfactory bulb, and septo-preoptic area. These results indicate that
      GnRH neurons originate in the olfactory placode and migrate into the
      telencephalon including the septo-preoptic area. A migratory route of GnRH
      neurons was well documented by the use of a quail neuron-specific antibody, QN.
      The migratory route in the brain is discussed with special reference to the
      terminal nerve. A GnRH-immunoreactive neuronal group of chick origin appeared in
      the diencephalon of chimeric embryos. These diencephalic neurons may be of non
      placodal origin. FMRFamide-immunoreactive neurons of quail origin were also found
      in the quail olfactory nerve and the host olfactory bulb, suggesting that
      FMRFamide neurons also originate in the olfactory placode and migrate into the
      brain.

PMID- 8874899
TI  - Developmental changes in axon terminals visualized by immunofluorescence for the
      growth-associated protein, GAP-43, in the robust nucleus of the archistriatum of
      the zebra finch.
AB  - Two afferents to the robust nucleus of the archistriatum (RA) are important for
      song learning by the zebra finch. The growth-associated protein-43 (GAP-43) has
      been used as a molecular marker for axonal growth. In these experiments, the axon
      terminals were visualized by immunofluorescence with antibodies against GAP-43
      and we studied the developmental processes in the zebra finch after the invasion
      of the RA by afferent fibers. After waiting at the dorsal border of the RA before
      invading the RA, the axon terminals from the higher vocal center (HVc) first
      contacted the soma, and then redistributed and established synapses on the
      dendrites. This initial contact with the soma may be closely related to the
      neurotrophic properties of the axon terminals from the HVc neurons.

PMID- 8874900
TI  - Absence of postnatal testosterone fails to demasculinize the male rat's corpus
      callosum.
AB  - We had previously shown that elimination of testosterone from embryonic day 17
      through adulthood reduced the midsagittal area of the male rat corpus callosum
      (CC). However, day 1 castration, performed after the 2-h post-birth testosterone
      surge, was without effect. To elucidate the contribution of this surge on the CC,
      male rats were delivered by cesarean section and castrated within 20 min. This
      procedure eliminated the 2-h postnatal rise in testosterone levels. The prenatal
      surge in testosterone, which occurs on embryonic day 18, remained intact. In
      adulthood, callosal area was examined in castrate males, sham males, and intact
      females. Castrate males and sham males had significantly larger CCs as compared
      to females. The two male groups did not differ from each other. Body weight was
      significantly higher in sham versus castrate males, establishing the
      effectiveness of the castration. These results show that hormonal organization of
      the CC in the male is the result of the independent action of prenatal testicular
      androgens, and suggest that the end of this period marks the end of callosal
      sensitivity to testicular hormone influence. In addition, this report documents
      sexual dimorphism of the CC in a third rat strain.

PMID- 8874901
TI  - Long-term effects of excitatory amino acid antagonists NBQX and MK-801 on the
      developing brain.
AB  - Because of the critical role of excitatory amino acids (EAAs) in epileptogenesis
      and seizure-induced brain damage, EAA antagonists are now being considered as a
      possible therapy for seizures. However, during development EAAs play a pivotal
      role in learning, memory, and brain plasticity. To evaluate the long-term effects
      of a short course of EAA antagonists on the developing brain, a non-NMDA
      antagonist, NBQX, or a NMDA antagonist, MK-801, were administered over 7 days by
      osmotic pumps stereotaxically implanted into the lateral ventricles of normal 10
      day old rats. Alternatively, 10 and 20 day old rats received a 7 day course of
      intraperitoneal (i.p.) NBQX. One month later, the NBQX-, MK-801-treated rats, and
      controls underwent a series of behavioral studies: handling test, open field, and
      Morris water maze. Flurothyl inhalation was used to test seizure susceptibility
      in all groups. Although all of the rats treated with NBQX via osmotic pumps has
      spontaneous seizure, rats surviving infusion of EAAs had no deficits in learning,
      memory, or behavior and did not differ from controls in seizure susceptibility
      with flurothyl. In the developing animal, a short-term course of EAA antagonists
      leads to no long-term adverse effects on behavior or seizure susceptibility.

PMID- 8874902
TI  - Spatiotemporal expression of CD15 in the developing chick retina.
AB  - The spatiotemporal distribution pattern of the carbohydrate epitope CD15 was
      examined in the developing chick retina. CD15 expression appeared for the first
      time at E13 in the INL and GCL. The developmental profile of the INL, from E13 to
      E16, showed increasing numbers of stratified amacrine cells, whereas diffuse
      amacrine subtypes appeared later, beginning at E15. Smaller populations of
      bipolar cells were seen at E17. Three types of CD15-positive ganglion cells could
      be differentiated by E15. A gradient in the appearance of identified
      immunoreactive amacrine cells extended from the dorsotemporal to the ventral and
      nasal retina. The adult-like pattern of CD15 expression did not become
      established until E19. Adult-like densities of immunoreactive cells were reached
      toward the end of the embryonic period between E18 in the dorsotemporal and
      ventral retina, and E19 in the dorsonasal retina. In the adult-like retina,
      labelled cells became particularly numerous at its greatest circumference, and
      were most densely packed in the dorsotemporal retinal quadrant. From E16 to P5,
      three membrane-bound, CD15-positive glycoproteins of 20, 32 and 34 kDa were
      identified by Western blots. The time course in the appearance of the membrane
      associated CD15 recognition molecule on differentiating amacrine, bipolar and
      ganglion cells is correlated to the establishment of synaptic contacts.

PMID- 8874903
TI  - Fluid percussion brain injury in the developing and adult rat: a comparative
      study of mortality, morphology, intracranial pressure and mean arterial blood
      pressure.
AB  - Changes in intracranial pressure (ICP) and mean arterial blood pressure (MABP)
      were measured for 30 min following an experimental fluid percussion traumatic
      brain injury in postnatal day 17 (P17), P28 and adult rats. Under enflurane
      anesthesia the left femoral artery was cannulated for MABP measurements and a 20
      gauge needle was stereotaxically positioned into the right lateral ventricle for
      ICP measurements. Three different injury severities (mild: 1.35-1.45 atm,
      moderate: 2.65-2.75 atm, severe: 3.65-3.75 atm) were delivered over the left
      parietal cortex to each of the age groups. The biomechanical/physiological
      results indicated that fluid percussion generated reproducible traumatic brain
      injuries in the developing rat. Furthermore, with increasing injury severity the
      physiological responses (in terms of ICP and MABP) became more pronounced,
      resulting in a corresponding increase in mortality (mild, moderate, severe,
      respectively, P17: 27%, 36%, 100%; P28: 33%, 30%, 75%; adult: 0%, 20%, 55%).
      Compared to adult animals, developing rats exhibited pronounced hypotension in
      response to closed head injury, which most likely explains the greater percent
      mortality among the younger animals. The utilization of this model will allow for
      future studies addressing the consequences of traumatic brain injury when it is
      sustained early in development.

PMID- 8874904
TI  - Recurrent seizures in immature rats: effect on auditory and visual
      discrimination.
AB  - The effect of recurrent seizures in developing rats on subsequent long-term
      behavior was studied. Fifteen day old rats received a convulsant dosage of
      flurothyl three times daily for five consecutive days. When the rats were fully
      mature, they underwent behavioral testing using the water maze and auditory
      quality or location discrimination. With serial flurothyl administration seizure
      duration increased progressively but latency to seizure onset did not change.
      Compared to controls, flurothyl-treated rats had impaired performance in the
      water maze and on auditory location, but not on quality discrimination.
      Histological examination showed no gross cell loss in the hippocampus. This study
      demonstrates that serial seizures in the developing brain cause detrimental
      effects on visual and auditory spatial learning.

PMID- 8874905
TI  - Comparison of sevoflurane/fentanyl and isoflurane/fentanyl during elective
      coronary artery bypass surgery. Sevoflurane Venture Group.
AB  - PURPOSE: Due to the progressive aging of the surgical population, the proportion
      of patients with coronary artery disease (CAD) is likely to increase. The effects
      of the new inhalational anaesthetic sevoflurane must be determined in patients
      with known CAD. METHODS: This multicentre, randomized, open-label study compared
      the haemodynamic and cardiovascular effects of sevoflurane and isoflurane with
      fentanyl in 284 ASA physical status II-IV patients undergoing elective coronary
      artery bypass graft (CABG). RESULTS: Satisfactory records were available in 272
      patients, 139 sevoflurane (Group S) and 133 isoflurane (Group I). There were no
      differences between groups for demographic data except that more patients in
      Group S were taking preoperative beta-blockers (P = 0.03). The mean end-tidal MAC
      and MAC.hr requirements between groups were not different (Group S received 0.63
      +/- 0.02 MAC and 1.00 +/- 0.05 MAC. hr while Group I received 0.58 +/- 0.02 MAC
      and 0.92 +/- 0.05 MAC. hr P = NS). The preCPB use of intravenous fentanyl was not
      different between groups. There was a similar decrease in haemodynamic variables
      in both groups after induction that persisted throughout the preCPB period. The
      incidence of preCPB myocardial ischaemia, adverse haemodynamic events and use of
      vasoactive drugs did not differ between groups. The incidence of postoperative
      myocardial infarction was 2.2% for Group S and Group I was 4.5% (P = NS). There
      were five postoperative deaths, one of which was attributed to a cardiac cause
      (Group I). CONCLUSION: In patients undergoing elective CABG with low risk
      factors, either sevoflurane or isoflurane, combined with fentanyl, provided an
      acceptable preCPB haemodynamic profile and cardiac outcomes.

PMID- 8874906
TI  - Oral clonidine reduces postoperative PCA morphine requirements.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of perioperative
      oral clonidine on postoperative analgesia and PCA morphine requirements in adult
      patients after major orthopaedic knee surgery. METHODS: In this prospective,
      double blind, placebo-controlled study 44 patients undergoing either total knee
      replacement or hemiarthroplasty of the knee were randomly assigned to receive
      oral placebo or clonidine (5 micrograms . kg-1) 1.5 hr before surgery, and at 12
      hr, and 24 hr after the initial dose. Five patients were subsequently withdrawn
      from study. No other preoperative drugs were given. Preoperative sedation score
      was recorded. A standardized general anaesthetic was administered to all
      patients. Postoperative blood pressure, heart rate, PCA morphine use, visual
      analogue score (VAS) for pain, sedation, nausea, and pruritus were recorded for
      36 hr postoperatively. RESULTS: The cumulative PCA morphine used was 37% lower
      after clonidine 57.3 +/- 26.8 mg (mean +/- SD) compared with placebo 91 +/- 31.6
      mg (P = 0.031). There was no difference in pain or sedation scores
      postoperatively but patients who received clonidine were more sedated
      preoperatively (P < 0.001) and had a lower mean arterial blood pressure
      throughout the period of study by 10 to 26 mmHg (P < 0.0001). Clonidine reduced
      the incidence of postoperative nausea (25% vs 74%) (P < 0.01) and vomiting
      compared with placebo (10% vs 53%) (P < 0.01) and required less antiemetic
      (dimenhydrinate 37.5 +/- 20.9 mg vs 82.1 +/- 49.4 mg) but not statistically
      significant (P = 0.065). CONCLUSIONS: Oral clonidine is a useful component to
      postoperative balanced analgesia as it decreases PCA morphine requirements and
      decreases the incidence of nausea and vomiting.

PMID- 8874907
TI  - Epidural administered buprenorphine in the perioperative period.
AB  - PURPOSE: To study the effect of epidural buprenorphine on minimum alveolar
      concentration (MAC) of volatile anaesthetics, duration of analgesia and
      respiratory function in the perioperative period. METHODS: One hundred and twenty
      patients, ASA I-II undergoing gynaecological surgery were randomly divided into
      three studies. The forty patients in each study were randomly divided into four
      groups depending on the dosage; Group I (control), Group II (80 micrograms. kg-1
      morphine), Group III (4 micrograms. kg-1 buprenorphine), Group IV (8 micrograms.
      kg-1 buprenorphine). The MAC of halothane was measured following epidural
      administration of the agents in each group. The duration of analgesia was
      assessed by the first request for pentazocine. Postoperative analgesic effects
      were assessed by the total dosage of pentazocine required for the 48 hr after
      surgery. Respiratory rate (RR), minute volume (MV), and PaCO2 were measured
      during surgery and the postoperative period. The MAC of halothane was reduced in
      Group IV (P < 0.01). The duration of analgesia was 10.0 +/- 5.1 hr (Mean +/- SE)
      in Group I, 37.7 +/- 4.7 hr in Group II, 27.1 +/- 7.1 hr in Group III, and 44.4
      +/- 4.1 hr in Group IV. Total dosage of pentazocine was lower in Group IV (P <
      0.05) than in the other groups. The decrease of RR, MV and the increase of PaCO2
      were observed within 60 min in Group III and IV dose dependently. CONCLUSION:
      Epidural buprenorphine administered in a dose of 4 or 8 micrograms. kg-1 provides
      postoperative analgesia that is no less effective than that of morphine.

PMID- 8874908
TI  - Wound infiltration with lidocaine prolongs postoperative analgesia after
      haemorrhoidectomy with spinal anaesthesia.
AB  - PURPOSE: There are few clinical data examining whether sensitization of
      peripheral nerves contributes to postoperative pain when the entry of noxious
      impulses to the central nervous system is blocked. We hypothesized that wound
      infiltration with lidocaine would provide better postoperative analgesia than
      with normal saline following haemorrhoidectomy with spinal blockade. METHODS: In
      a randomized, placebo-controlled, blinded study, 168 adults undergoing
      haemorrhoidectomy were allocated to two groups. In Group L (n = 88) local
      infiltration was provided with lidocaine 1% and in Group S (n = 80) with normal
      saline. Following spinal anaesthesia with lidocaine 3%, the surgeon infiltrated
      15 ml of either infiltration solution to the surgical area. Postoperative
      analgesia was obtained by continuous epidural administration of 90 mg eptazocine
      in normal saline for 48 hr. Supplemental analgesics were given on request.
      Postoperative pain control was assessed at rest and during coughing with a 10 cm
      VAS on the 1st, 2nd, and 3rd postoperative days (POD). RESULTS: The VAS scores at
      rest in Group L were lower than those in Group S throughout the postoperative
      period. During coughing, VAS scores in Group S were increased on the 3rd
      postoperative day, while those in Group L remained constant (4.42 +/- 0.27 vs
      3.14 +/- 0.28, P < 0.05). Fewer patients in Group L than in Group S required
      supplemental analgesics. CONCLUSION: Preoperative lidocaine infiltration to the
      surgical area provided prolonged postoperative analgesia in patients receiving
      haemorrhoidectomy with spinal anaesthesia.

PMID- 8874909
TI  - Patient maintained alfentanil target-controlled infusion for analgesia during
      extracorporeal shock wave lithotripsy.
AB  - PURPOSE: The purpose of this study was to determine whether alfentanil given by a
      pharmacokinetic-based target controlled infusion (TCI) system under patient
      control is a suitable analgesic technique for extracorporeal shock wave
      lithotripsy (ESWL). METHODS: The design was an open, unblinded, noncomparative,
      prospective study. Forty outpatients undergoing ESWL were given patient
      maintained alfentanil TCI. Pain, nausea and sedation were assessed every 300
      shocks. Vital signs were recorded every three minutes, pulse oximetry and
      electrocardiography being monitored continuously. Blood alfentanil concentration
      was measured for comparison with the predicted value. RESULTS: Alfentanil
      consumption (median 1.34 mg, range 0.8-3.6) and measured levels following
      treatment (median 60 ng.ml-1, range 15.6-134.3) varied widely. The precision of
      the TCI system and the median prediction error (bias) were both 49%. The median
      of pain scores recorded during treatment was 4 (range 0-8). The median
      respiration rate was 15 bpm (range 10-23), three patients required oxygen (SaO2 <
      92%) cardiovascular measurements were stable and there was no excessive sedation.
      The incidence of nausea was 15%. All patients were ready for hospital discharge
      within one hour following treatment. CONCLUSIONS: Patient maintained alfentanil
      TCI provides good analgesia for ESWL in the majority of patients with little
      sedation. Respiratory depression is uncommon but supplementary oxygen should be
      given prophylactically. There is considerable interindividual variation in demand
      for alfentanil indicating the usefulness of the patient control method. The TCI
      system underestimated alfentanil blood concentrations but this did not affect its
      clinical usefulness.

PMID- 8874910
TI  - Evaluation of cisatracurium, a new neuromuscular blocking agent, for tracheal
      intubation.
AB  - PURPOSE: The primary objective of this study was a blinded, randomized comparison
      of the recommended intubating dose of atracurium (0.5 mg. kg-1) with an
      approximately equipotent dose of cisatracurium (0.1 mg. kg-1) during
      N2O/O2/propofol/fentanyl anaesthesia. METHODS: Eighty ASA physical status 1 or 2
      patients, 18-70 yr of age, within 30% of ideal body weight, scheduled for
      elective low to moderate risk surgical procedures were studied. Adductor pollicis
      evoked twitch responses were measured with a Grass FT 10 force displacement
      transducer (Grass Instruments, Quincy, MA) and continuously recorded on a Gould
      multichannel polygraph (Gould Instrument Systems, Cleveland, OH) after induction
      of anaesthesia. RESULTS: Increasing the initial dose of cisatracurium (from 0.1
      to 0.15 and 0.2 mg. k-1, decreased mean time of onset (from 4.6 to 3.4 and 2.8
      min, respectively), and increased mean time of clinically effective duration (45
      to 55 and 61 min, respectively). Recovery to a T4:T1 ratio of 0.7 occurred
      approximately seven minutes following administration of the reversal agent
      neostigmine for all treatment groups. Intubation conditions were good or
      excellent in over 90% of patients in all treatment groups (two minutes after
      approximately 2 x ED95 doses of cisatracurium or atracurium and 1.5 minutes after
      3 x and 4 x ED95 doses of cisatracurium). CONCLUSION: The intubation results
      reported in this study together with the combination of predictable recovery from
      neuromuscular block and apparent haemodynamic stability make cisatracurium a
      potentially useful muscle relaxant in clinical practice.

PMID- 8874912
TI  - A comparison of ondansetron and prochlorperazine for the prevention of nausea and
      vomiting after tympanoplasty.
AB  - PURPOSE: To evaluate the effects on PONV and headache after tympanoplasty of
      prochlorperazine 0.2 mg.kg-1 i.m., ondansetron 0.06 mg.kg-1 i.v. or placebo
      (isotonic saline) 0.02 ml.kg-1 i.v. given immediately after induction of
      anaesthesia prior to tracheal intubation. METHODS: The study was randomised,
      double blind and prospective. One hundred and forty-eight patients, aged 9-61 yr,
      received a standardised balanced inhalational anaesthetic with controlled
      ventilation and induced hypotension. Postoperatively, the frequencies of retching
      and vomiting in the PACU and of nausea, retching, vomiting, headache, analgesic
      and antiemetic requirements in the surgical ward for 24 hr were recorded.
      RESULTS: The four test groups (n = 37 each) were comparable. The incidences of
      vomiting in the PACU were similar. During the first 24 hr after surgery the
      antiemetics produced no reductions in the incidence of nausea alone or of
      vomiting alone. However, the combination of nausea and vomiting was reduced from
      53% (placebo) to 16% (P < 0.0005), 19% (P < 0.0005) and 30% (P < 0.05) by i.m.
      prochlorperazine, i.v. ondansetron and i.v. prochlorperazine, respectively. The
      frequency of those experiencing no PONV was increased from 27% (placebo) by
      prochlorperazine i.m. to 57% (P < 0.01), by ondansetron i.v. to 62% (P < 0.005)
      and by prochlorperazine i.v. to 43% (P = NS). The onset of PONV was delayed in
      those given prochlorperazine im, and vomiting was less severe in those given
      ondansetron i.v. Headache occurred with similar frequency in each group.
      CONCLUSION: Prophylactic prochlorperazine 0.2 mg.kg-1 i.m. and ondansetron 0.06
      mg.kg-1 i.v. are similarly efficacious in reducing nausea with vomiting after
      tympanoplasty, while prochlorperazine 0.1 mg.kg-1 i.v. is less efficacious.
      Neither drug given as described appeared to reduce the frequency of postoperative
      nausea alone or vomiting alone.

PMID- 8874911
TI  - Optimum time for neostigmine reversal of atracurium-induced neuromuscular
      blockade.
AB  - PURPOSE: The aim of the study was to determine the optimum time for
      administration of neostigmine during recovery from atracurium-induced
      neuromuscular blockade. METHODS: The study comprised 103 patients anaesthetised
      with midazolam, fentanyl, thiopentone, halothane, and nitrous oxide. Relaxation
      was induced with atracurium 0.5 mg. kg-1 and maintained with supplements of 0.15
      mg. kg-1. The ulnar nerve was stimulated with train-of-four (TOF) and double
      burst stimulation (DBS). Evoked MMG responses were recorded. Patients were
      randomized to spontaneous recovery (n = 20) or to assisted recovery by
      neostigmine (0.07 mg.kg-1) at varying intervals (6-50 min) from the last
      atracurium dose (n = 83). RESULTS: The reversal time (time from administration of
      neostigmine to TOF ratio 0.7) was always < 13 min, when T1 (first twitch in TOF)
      was detectable or when D1 (first twitch in DBS) was > 5%. Total assisted recovery
      time (time from last supplemental atracurium dose to TOF ratio 0.7) increased
      with increasing T1 and D1 twitch heights (P < 0.05). The curve fitted to the
      scattergram with total assisted recovery time vs time from last atracurium
      supplement to neostigmine administration decreased to reach a minimum after which
      it increased to approach the line of identity. The minimum of the curve (total
      assisted recovery time 30.7 min) was reached when neostigmine was given 18.6 min
      after last atracurium supplement. At this time the T1 and D1 twitch height
      averaged 4 and 8% respectively. If prolongation of the minimum total recovery
      time of 2.5% is accepted, neostigmine can be given at T1 and D1 twitch height
      values of 0 to 8% and 4 to 15%, respectively. CONCLUSION: The optimum time for
      neostigmine administration, taking both the reversal time and total recovery time
      into consideration, is when 0 < T1 < 8% or when 5 < D1 < 15%. Giving neostigmine
      at more profound degrees of blockade prolongs reversal time, while giving
      neostigmine later in the recovery phase prolongs total recovery time.

PMID- 8874913
TI  - Midazolam and awareness with recall during total intravenous anaesthesia.
AB  - PURPOSE: A double-blind study was undertaken to evaluate the influence of graded
      doses of midazolam on propofol infusion requirements, recovery characteristics
      and the quality of recovery, associated with propofol/alfentanil/O2 total
      intravenous anaesthesia (TIVA). METHODS: Ninety ASA Class I and II subjects
      scheduled for arthroscopic knee surgery were randomly allocated to receive either
      placebo (Group PLAC), or midazolam doses of 15, 30 or 45 micrograms.kg-1 (Groups
      M-15, M-30 and M-45, respectively). Anaesthesia was induced and maintained with
      propofol (infused initially at 100 micrograms.kg-1.min-1, and adjusted there
      after according to anaesthetic depth) and alfentanil (loading dose of 20
      micrograms.kg-1, followed by infusion at 0.5 microgram.kg-1. min-1).
      Postoperatively, times to awakening, recovery, and discharge were evaluated, in
      addition to psychometric evaluations using the Trieger Dot Test (TDT). RESULTS:
      The study was discontinued prematurely, as six patients unexpectedly experienced
      intraoperative awareness with recall (4/21 = 19.1% of patients with PLAC vs 2/69
      = 2.9% of patients in the midazolam groups, P < 0.04). Induction requirements of
      propofol were found to be lower in the M-30 and M-45 groups when compared with
      PLAC (P < 0.05), whereas propofol infusion requirements were similar among
      groups. Times to awakening and discharge from the Recovery Room and Day Care
      Unit, as well as TDT scores, were no greater in any midazolam group than in PLAC.
      CONCLUSIONS: Midazolam 30-45 micrograms.kg-1 decreases the amount of propofol
      required for anaesthetic induction, without influencing recovery profiles or
      patient discharge times from the Day Care Unit. Despite careful modulation of the
      propofol infusion rate, six patients unexpectedly experienced intraoperative
      awareness with recall, with the lowest incidence occurring in those groups where
      patients had received midazolam.

PMID- 8874914
TI  - Dorsal penile nerve block in children undergoing circumcision in a day-care
      surgery.
AB  - PURPOSE: Circumcision is performed under general anaesthesia (GA) with dorsal
      penile nerve block (DPNB) as an analgesic technique for postoperative pain. The
      purpose of this study was to compare DPNB as the sole anaesthetic procedure vs GA
      and DPNB for circumcision in children as an outpatient procedure. METHODS: In a
      six-month prospective study, 250 boys aged 6 to 17 yr (mean age 11.5 +/- 3.5 yr)
      were randomized into two groups. Group A (n = 122) received DPNB only prior to
      circumcision, and Group B (n = 128) received GA + DPNB. The groups were compared
      for complications of the block, effectiveness of anaesthesia, operating room
      time, postoperative time and ease of recovery. RESULTS: There were no major
      operative complications in the two groups. Minor block complications, including
      oedema and haematoma, occurred in 16 (13.1%) boys in Group A and 27 (21.10%) boys
      in Group B (NS). At surgery, 3 (2.6%) from Group A received additional GA and 1
      (0.8%) received additional local anaesthesia. They represent a DPNB failure rate
      of 3.3%. Mean operating room time was 11 +/- 2.5 min in Group A and 19 +/- 3.5
      min in Group B, and post-anaesthesia care unit (PACU) time was 51 +/- 10 min in
      Group A and 101 +/- 14.5 min in Group B (P < 0.001). Nausea and vomiting in the
      PACU were noted in one patient in Group A and in 15 in Group B (P < 0.05). Only
      patients in Group B required additional analgesia and tranquilizers in the PACU
      (0 versus 20; P < 0.05). CONCLUSIONS: These data confirm that DPNB has advantages
      over GA + DPNB for paediatric circumcision in day-care surgery.

PMID- 8874915
TI  - Anaesthetic management of a parturient with severe muscular dystrophy, lumbar
      lordosis and a difficult airway.
AB  - PURPOSE: This case describes the management of a 19-yr-old wheelchair bound
      primigravida with severe muscular dystrophy who presented for Caesarean section
      after spontaneous rupture of membranes. Anaesthesia was influenced by several
      features of her systemic disease which were impediments to both neuraxial and
      general anaesthesia. CLINICAL FEATURES: Other than for a prenatal record and the
      history obtainable from the patient, little additional medical information was
      available. Physical examination showed diffuse muscular weakness and an
      anatomically abnormal airway. Examination of the spine showed slight 10-15
      degrees thoracolumbar scoliosis and > 45 degrees lumbar lordosis. Fetal
      assessment was normal. Echocardiography revealed mildly decreased left
      ventricular function and was consistent with pulmonary hypertension. After
      discussion with the patient and her obstetrician, elective Caesarean delivery was
      deemed the best management. Neuroaxial anaesthesia was at an increased risk of
      failure due to the profound lumbar lordosis. A plan for awake intubation and
      general anaesthesia was described to the patient in case regional anaesthesia
      could not be initiated. A fibreoptic bronchoscope and difficult intubation kit
      were made available. General anaesthesia was expected to have increased risk of
      postoperative pulmonary complications, hence epidural anaesthesia was attempted.
      After difficult catheter insertion, a sensory block was titrated to a T4 level.
      This was well tolerated by both mother and fetus. A healthy baby was delivered
      with Apgar scores of 9 and 9. Postoperatively the mother was transferred to the
      intensive care unit. After 72 hr, the patients respiratory status allowed
      transfer to the word. CONCLUSION: This case illustrates the use of epidural
      anaesthesia in the successful management of a severely compromised patient with
      limb-girdle muscular dystrophy undergoing elective Caesarean section.

PMID- 8874916
TI  - Supine approach to the sciatic nerve in the popliteal fossa.
AB  - PURPOSE: Sciatic nerve block in the popliteal fossa (popliteal nerve block, PNB)
      is an anaesthetic technique well-suited for operations below the knee. However,
      difficulty with positioning the patient in the prone position often precludes the
      classical, posterior approach to the block. In this report, an alternative
      approach to PNB that can easily be performed with a patient in the supine
      position is described. CLINICAL FEATURES: Three patients in whom the clinical
      circumstances precluded the use of the classical approach to PNB are described.
      In each case, PNB was performed using the alternative, supine approach. With a
      patient in the supine position, the leg is flexed at both the hip and knee, and
      supported by an assistant. After the anatomical landmarks of the popliteal fossa
      are identified, an insulated needle attached to a peripheral nerve stimulator is
      inserted 7 cm above the popliteal crease, 1 cm laterally to the midline and
      directed 45 degrees cephalad. Upon obtaining either dorsal or plantar flexion of
      the foot at the output current of 0.5 mAmp or less. 30-40 ml of local anaesthetic
      solution are injected. CONCLUSION: The supine approach to PNB allows the use of
      the block in patients that cannot be positioned in the prone position. Flexion of
      the leg at the knee greatly facilitates identification of the anatomical
      landmarks. When combined with a block of the femoral or saphenous nerve, this
      technique provides excellent anaesthesia for patients undergoing foot and ankle
      surgery.

PMID- 8874917
TI  - The anaesthetic management of a patient with Emery-Dreifuss muscular dystrophy.
AB  - PURPOSE: This case report presents a patient with Emery-Dreifuss Muscular
      Dystrophy and describes the anaesthetic considerations. CLINICAL FEATURES: The
      features of Emery-Dreifuss Muscular Dystrophy are contractures, humeroperoneal
      muscle weakness and cardiomyopathy. The anaesthetic considerations for this
      syndrome are difficult tracheal intubation, difficult spinal anaesthetic, heart
      block, gastric reflux, rhabdomyolysis, and unproved malignant hyperthermia
      susceptibility. CONCLUSION: The major anaesthetic problem for the patient with
      Emery-Dreifuss Muscular Dystrophy could be a life-threatening cardiomyopathy.

PMID- 8874918
TI  - Cardiac arrest during removal of a pulmonary artery catheter.
AB  - PURPOSE: This case report describes an asystolic cardiac arrest that occurred
      during removal of a pulmonary artery (PA) catheter. CLINICAL FEATURES: A 70-yr
      old man underwent elective hepatectomy because of hepatic carcinoma with a
      combination of thoracic epidural blockade and general anaesthesia. After the
      conclusion of the operation, the PA catheter was removed and immediately after,
      the patient developed profound sinus bradycardia and hypotension followed by
      asystolic cardiac arrest. Two minutes after the onset of asystole, cardiac rhythm
      was detected following the administration of epinephrine and atropine. He had no
      further episodes of bradycardia or neurological deficit. CONCLUSION: Removal of a
      PA catheter has the potential of inducing asystole requiring cardiac
      resuscitation and availability of emergency drugs.

PMID- 8874920
TI  - A simple method to decrease malposition of Robertshaw-type tubes.

PMID- 8874919
TI  - Antinociceptive synergistic interaction between morphine and n omega-nitro 1
      arginine methyl ester on thermal nociceptive tests in the rats.
AB  - PURPOSE: This study was conducted to demonstrate if subeffective dose of N omega
      Nitro L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor,
      interacts with morphine when given intrathecally (IT), epidurally (EP), and
      intravenously (IV) to produce a synergistic antinociceptive effect in normal
      rats. METHODS: Chronically catheterized 72 male Wistar rats were used in this
      study. We measured the tail flick latency in response to thermal stimulation of
      the tail on a hot plate (53 degrees C), and determined dose-response functions of
      IT, EP and IV morphine, L-NAME, and morphine co-administered with subeffective
      doses of L-NAME. The antinociceptive effect was evaluated using the doses for 50%
      maximum probable effect (ED50). The interaction between morphine and L-NAME was
      evaluated using an isobolographic approach. ANOVA was used for the statistical
      analysis. Significance was taken at P < 0.05. RESULTS: Morphine and L-NAME
      produced dose-related antinociceptive effects in the IT (ED50 = 1.23 +/- 0.18
      micrograms (Mean +/- SEM) and 76.0 +/- 14.5 micrograms), EP (ED50 = 32.6 +/- 2.4
      micrograms and 560 +/- 97 micrograms), and IV (ED50 = 563 +/- 71.8 micrograms and
      16.0 +/- 4.0 mg) groups, respectively. Co-administration of small doses of L-NAME
      and morphine produced reductions in the ED50 values for morphine (0.16 +/- 0.03
      microgram in IT, 1.18 +/- 0.32 micrograms in EP, and 50.5 +/- 11.4 micrograms in
      IV groups) (P < 0.01), suggesting a multiplicative interaction of L-NAME with
      morphine. CONCLUSION: L-NAME has a synergistic antinociceptive interaction with
      morphine in response to thermal stimulation when given intrathecally, epidurally
      or intravenously in rats.

PMID- 8874921
TI  - Graduated compression stocking prevents hypotension during spinal anaesthesia.

PMID- 8874922
TI  - Vitalert 3200 Capnometer alarm.

PMID- 8874923
TI  - Technique and strategy of rotational atherectomy.
AB  - Atherosclerotic plaque heterogeneity has created the need for the development of
      second generation devices aimed specifically at lesions where PTCA has been shown
      to be suboptimal. The Rotablator system represents one of the newer technologies
      which utilizes plaque ablation to achieve larger lumens. The device is a high
      speed "rotary sander," which requires the interventional cardiologist to be
      keenly aware of the mechanical implications while advancing the device through
      the coronary vasculature. The objective of this article is to review the most
      recent technique refinements and strategies for rotational atherectomy as well as
      the available clinical data and ongoing clinical trials.

PMID- 8874924
TI  - Coronary physiology of percutaneous rotational atherectomy.
AB  - Integration of coronary blood flow velocity measurements into interventional
      procedures has enhanced our understanding of coronary flow dynamics. The coronary
      physiology of rotational atherectomy, with and without adjunctive coronary
      angioplasty, has not been well-defined. This review describes the coronary
      physiology induced by rotational atherectomy. Serial coronary blood flow and
      translesional hemodynamics, measured following rotational atherectomy and again
      after adjunctive balloon angioplasty, indicate that coronary blood flow and flow
      reserve may not be normalized despite significant angiographic improvements after
      rotational atherectomy alone and after adjunctive balloon angioplasty.

PMID- 8874925
TI  - Incremental value of intravascular ultrasound during rotational coronary
      atherectomy.
AB  - During the last several years, major improvements in intravascular ultrasound
      image quality have led to new and important information about the clinical
      application of rotational atherectomy. Ultrasound is providing data on the
      mechanism of luman enlargement, burr sizing, and the effects of the procedure on
      different plaque morphologies. This information is often important for optimizing
      device selection and procedural success, as well as for minimizing complications.
      In this review we first discuss the currently available data regarding the
      mechanisms of lumen enlargement following rotational ablation and the
      implications of these findings for lesion and patient selection. We review how
      this data is modifying several of the technical aspects of the rotational
      ablation procedure in the interventional laboratory. We than assess the available
      data that suggest that preprocedural ultrasound examination may eventually help
      to identify lesions at high risk for adverse outcome with stand-alone balloon
      angioplasty or stent placement. These ultrasound data may help triage many of
      these targets to initial debulking with rotational ablation. Finally, we review
      data that suggest that ultrasound analysis has important implications for
      comparative trials of new devices, particularly trials of the Rotabalator.

PMID- 8874926
TI  - High-speed rotational atherectomy for chronic total coronary occlusions.
AB  - Treatment of chronic total occlusions remains a limitation of percutaneous
      revascularization and is associated with lower immediates success and higher long
      term restenosis rates compared to less severe stenoses. While part of the problem
      in dealing with total occlusions relates to successfully passing a wire across
      the occluded segment, most chronic occlusions contain large plaque burdens.
      Balloon dilatation sometimes falls to restore antegrade flow and often yields
      suboptimal angiographic results in these situations. Rotational atherectomy has
      proven useful in treating calcified and diffusely-diseased vessels and appears
      attractive for debulking lesions with large atheromatous plaques. We report our
      experience using rotational atherectomy in treating chronic total occlusions.

PMID- 8874927
TI  - Coronary hemodynamics before and after rotational atherectomy with adjunctive
      balloon angioplasty.
AB  - The phenomenon of "no-reflow" has been described frequently after rotational
      atherectomy. The aim of this study was to determine the coronary hemodynamic
      changes by Doppler flow wire before and after rotational atherectomy and
      adjunctive balloon angioplasty in 10 patients. All patients had TIMI-III flow at
      baseline. After rotational atherectomy alone, two patients had TIMI-I, four
      patients had TIMI-II, and four patients had TIMI-III flow. In addition, the
      number of Cineframes to Opacification of a preselected distal landmark increased
      twofold (from 49 +/- 12 to 118 +/- 27 frames; P < 0.05). Intracoronary
      nitroglycerin and verapamil was associated with return to baseline of both
      measurements. Following adjunctive balloon angioplasty, there was an increase in
      lumen diameter (1.29 +/- 0.1 vs. 2.6 +/- 0.1 mm; P < 0.05), coronary flow (81 +/-
      14 to 154 +/- 18 ml/min; P < 0.05), maximal absolute velocity (23 +/- 4 to 52 +/-
      4 cm/sec; P < 0.05), and vascular resistance decreased (1.74 +/- 0.4 to 0.74 +/-
      0.4 mm Hg/ml/min; P < 0.05). However, no change in coronary flow reserve was
      noted (1.24 +/- 0.1 vs. 1.5 +/- 0.3). Immediately after rotational atherectomy
      alone, there is a reduction in angiographically determined coronary flow,
      suggesting either distal microvascular spasm or distal microvascular obstruction.
      Regardless of the mechanism, the transient reduction of coronary flow was rapidly
      reversed by coronary vasodilators. Despite the significant improvement of
      coronary hemodynamics noted immediately after combined rotational atherectomy and
      balloon angioplasty, coronary flow reserve remained abnormal. Similarly, no
      change in coronary flow reserve has been reported immediately after balloon
      angioplasty alone. The lack of improvement in flow reserve after both balloon
      angioplasty and rotational atherectomy suggests that the mechanisms of improved
      flow reserve may be device independent, and remain unexplained.

PMID- 8874928
TI  - Safety and efficacy of elective stent implantation following rotational
      atherectomy in large calcified coronary arteries.
AB  - Rotational atherectomy is an effective transcatheter therapy for calcified
      coronary lesions. In large (> 3-mm) calcified coronary arteries, stent
      implantation following rotational atherectomy may further improve acute and
      especially, long-term benefit. To determine the safety and efficacy of this
      device synergy approach, we studied 24 consecutive patients undergoing this
      procedure electively in native coronary arteries. Procedural success was achieved
      in 100% without any major ischemic complications. There was also no incidence of
      subacute thrombosis or cardiac event during 30-day follow-up period. Thus, we
      conclude that elective stent implantation following rotational atherectomy in
      large, calcified coronary arteries is safe and results in excellent clinical
      benefit up to 30 days.

PMID- 8874929
TI  - Coronary perforation complicating rotational ablation: the U.S. multicenter
      experience.
AB  - This study retrospectively analyzed the data within the U.S. Multicenter Registry
      for Rotational Ablation to determine the incidence of coronary perforation during
      rotational ablation, its angiographic predictors and clinical outcomes during
      2953 consecutive patients, 3717 lesions. Patients were categorized into Group A
      (without perforation, N = 2931) and Group B (with perforation, N = 22 patients).
      Perforation occurred in 0.7% of procedures, and in 0.6% of lesions treated and
      was more frequent within the right (12/ 1105, 1.1%) and circumflex (9/761, 1.2%)
      arteries than the left anterior descending artery [1/1727, 0.06%; (P < 0.001)].
      Morphologic features associated with increased perforation rates were
      eccentricity, tortuousity, and lesion length > 10 mm. Group B was assessed with
      regard to major complications, including death, surgery, myocardial infarction,
      or tamponade (type I); and minor complications; sealing with balloon angioplasty
      and without clinical sequelae (type II). There were 15 type I: emergency surgery
      in nine, of whom two died, and six infarctions (5 non-Q wave and one Q wave); and
      7 type II patients. Coronary perforation, although a rare complication of
      rotational ablation, is seen more frequently in the right and circumflex coronary
      arteries than the left anterior descending artery, and occurs more frequently
      with lesion eccentricity, tortuousity, and length > 10 mm.

PMID- 8874930
TI  - Forward slide maneuver: a new method of advancing the Rotablator system.
AB  - In performing coronary rotational ablation, advancing the Rotablator (Heart
      Technology, Redmond, WA) out of the guiding catheter and through a tortuous, non
      compliant vessel to reach the target lesion may be difficult and sometimes
      impossible without activation of the drive proximal to the target lesion. We
      report a technique not previously described for advancing the Rotablator to the
      target lesion before activating the drive by simultaneously advancing the burr
      control knob (slide) and the Teflon catheter sheath. Ten of 14 burrs (71%)
      ranging in size from 1.5 to 2.15 mm were successfully advanced in nine of ten
      (90%) cases in which the burr could not be advanced in the usual fashion
      (traction on the guidewire while advancing the sheath).

PMID- 8874931
TI  - Guidewire bias: potential source of complications with rotational atherectomy.
AB  - The guidewire in rotational atherectomy is an integral component in the ablative
      process. It functions not only to deliver the device but sets the cutting vector
      when the burr advances. Since the guidewire is a stiff stainless steel
      monofilament and the vessels are frequently tortuous and angulated, the guidewire
      may not be centrally oriented, but may bias preferentially to one side of the
      arterial wall. This may result in tangential or radial cutting. The following
      cases illustrate the dependence of the ablative process on the lie of the
      guidewire and the importance of integrating this factor in proper use of the
      Rotablator system.

PMID- 8874932
TI  - Cocktail attenuation of rotational ablation flow effects (CARAFE) study: pilot.
AB  - Although rotational ablation has been successful in the treatment of complex
      coronary lesions, periprocedural complications of microvascular-mediated ischemia
      (slow flow or no reflow) and coronary vasospasm may occur. In an attempt to
      reduce such complications, a drug cocktail consisting of a combination of
      verapamil 10 micrograms/ml, nitroglycerin 4 micrograms/ml, and heparin 20 U/ml
      was infused in 21 consecutive patients with AHA/ACC Type B2 and C lesion
      morphology. A total of 27 lesions were treated, with a procedural success rate of
      95%. One patient required emergency bypass surgery. Coronary vasospasm occurred
      in 7% (2/27 lesions). Only one lesion (3.7%) was associated with a transient
      reduction in TIMI flow that resolved within 5 min, and none had classical no
      reflow. No patient developed intraluminal thrombus, and none had hypotension
      requiring inotropic support. All patients had prophylactic temporary pacemakers
      inserted. All RCA and circumflex lesions and 50% of LAD stenoses required
      transient pacing. A "cocktail" infusion of verapamil, nitroglycerin, and heparin
      mixed in pressurized saline delivered through the 4-French Teflon sheath of the
      Rotablator system during rotational ablation is associated with high success and
      low complication rates. Transient AV block is frequent, especially when treating
      RCA and circumflex arteries; therefore, prophylactic pacing is indicated.

PMID- 8874933
TI  - Rotational atherectomy for treatment of in-stent restenosis: role of
      intracoronary ultrasound guidance.
AB  - In-stent restenosis is becoming increasingly frequent as greater numbers of
      intracoronary stents are implanted, and may pose a particularly challenging
      management problem. Recurrent restenosis following balloon angioplasty for in
      stent restenosis is common, and thus the possible role of debulking has been
      considered. This report describes the successful treatment of severe restenosis
      within a Palmaz-Schatz stent with high-speed rotational atherectomy, using
      intracoronary ultrasound guidance.

PMID- 8874934
TI  - Urgent rotational ablation of a partially protected, totally occluded left main
      coronary artery.
AB  - Coronary artery by-pass surgery (CABG) is considered the treatment of choice for
      patients with significant stenosis of the left main coronary artery. However,
      with reduction of the flow post-CABG, the left main may become totally occluded.
      This may become important once graft failure occurs. This case describes a
      patient who had by-pass surgery for critical left main stenosis and was re
      admitted four months later with graft failure and total occlusion of his left
      main, necessitating urgent rotational ablation of this partially protected,
      totally occluded left main coronary artery. This case raises the question of
      "prophylactic" left main angioplasty soon after surgery for critical left main
      stenosis, in order to eliminate the need for redo operation once graft failure
      occurs.

PMID- 8874935
TI  - High-speed rotational atherectomy of tortuous coronary arteries with guidewire
      associated pseudostenosis.
AB  - A series of high-speed rotational atherectomy cases is discussed in which
      pseudostenosis was noted following initial guidewire placement. The results and
      technical considerations when using the Rotablator in the setting of guidewire
      induced pseudostenosis are discussed.

PMID- 8874936
TI  - Distal vessel pullback angiography and pressure gradient measurement: an
      innovative diagnostic approach to evaluate the no-reflow phenomenon.
AB  - The angiographic appearance of "no-reflow" in saphenous vein grafts or native
      coronary arteries has been described following administration of thrombolytic
      therapy or performance of percutaneous transluminal coronary angioplasty or
      atherectomy. Apparent occlusion may represent spasm, dissection, thrombosis, or
      competitive collateral circulation, all of which must be excluded to make the
      diagnosis of "no-reflow." We describe an innovative approach to the diagnostic
      dilemma created by the appearance of "no-reflow" at coronary angiography.
      Pressure gradient measurement with distal vessel pull-back (retrograde)
      angiography provides maximal information regarding the severity of disease and
      the etiology of "no-reflow," while exposing both the patient and angiographer to
      less risk compared to standard strategies.

PMID- 8874937
TI  - Understanding the "no-reflow" problem.

PMID- 8874938
TI  - Women fare no worse than men 10 years after attempted coronary angioplasty.
AB  - A retrospective review of cardiac events occurring in all patients who underwent
      attempted coronary angioplasty in the first 5 years of our experience (1980-1985)
      was undertaken. Follow-up data were obtained from the civil registry, hospital
      records, patient, family, and referring physician. Patient survival curves were
      constructed and the outcome of women and men was compared. Eight hundred fifty
      six patients, 172 women and 684 men with a mean age of 60.0 and 55.3 years,
      respectively, underwent attempted coronary angioplasty with an overall procedural
      success rate of 82%, 77.7% in women and 83.1% in men. Follow-up data were
      obtained in 837 patients (97.8%) with a mean period of 9.6 years (range 0-13.3
      years). The estimated 10 year survival in women was identical to men [79%, 95%
      confidence interval (CI) 72.6-85.4% vs. 78%, 95% CI 74.6-81.4%] as was the 10
      year event-free survival (men 36%, 95% CI 32.0-40.0% vs. women 37%, 95% CI 29.2
      44.8%), with a similar proportion of major cardiac events-death, myocardial
      infarction, coronary artery bypass surgery, and repeat angioplasty. When women
      were matched to men for age and previous myocardial infarction, factors found to
      be associated with an adverse outcome, there was no significant difference.
      Additionally, outcome was compared after patients were matched for maximum
      nominal balloon size as an estimate of vessel size, with no significant
      difference between women and men. At follow-up, women complained of significantly
      more anginal symptoms than men (59.2% vs. 44.0%, P < 0.05) and took significantly
      more antianginal medication.

PMID- 8874939
TI  - How does the fairer sex fare after PTCA?

PMID- 8874940
TI  - Improved technique for use of half-stents remounted on a stent delivery system.
AB  - The use of half-length intracoronary Johnson & Johnson stents has been described
      in a number of settings. Half-stents are useful for very short lesions, avoidance
      of bifurcations or side-branches, ostial stenosis, covering gaps between adjacent
      stents, and for dissection adjacent to stents caused by postdilatation.
      Previously described methods for use of half-stents have involved bare stents, or
      significant manipulation of either the stent or the delivery sheath for remounted
      half-stents. We describe a method for half-stent preparation and delivery that
      does not involve distortion of the stent or the delivery sheath. The risk of
      stent loss, as can occur with bare stents, is diminished. The geometry of the
      stent is preserved since it is not expanded and then recrimped, and the end of
      the delivery sheath is not flared or distorted, which may interfere with stent
      delivery.

PMID- 8874941
TI  - Angiographic evidence of long-axis rotation in addition to short-axis
      aortopulmonary rotation: its implication in transposition of the great arteries.
AB  - To assess the pattern of aortic sinus in varied aortopulmonary rotations and its
      clinical implications, three aortic sinuses at the diastolic phase in true
      lateral view are identified in 53 angiograms of complete transposition of the
      great arteries recorded between 1988 and 1993. The patients with the high takeoff
      of the coronary arteries found at surgery and in the literature were selected for
      additional investigation. Six regions were defined on the horizontal plane. From
      left anterior 89 degrees to 61 degrees, the non-facing sinus moved toward the
      anterior aspect (one patient). From left anterior 60 degrees to left anterior 1
      degree, the left-hand sinus moved gradually from an anterior toward a posterior
      location (two patients). From directly anterior 0 degree to right anterior 59
      degrees, the right-hand sinus moved from posterior toward an anterior position
      (30 patients). From right anterior 60 degrees to right posterior 105 degrees, the
      non-facing sinus moved posteriorly (20 patients). On approaching directly
      anterior 0 degree and toward right anterior 60 degrees, the left-hand sinus was
      the lowest in anterior transposition of the great arteries instead of the non
      facing sinus, as in left anterior 90 degrees and in posterior transposition of
      the great arteries. High takeoff occurred commonly above the lowest left-hand
      sinus in anterior transposition of the great arteries (2 cases here and 5 in the
      literature, 100%). In conclusion, aortopulmonary rotations about the short and
      long axes were both evident on identification of the aortic sinus in various
      rotations. The aortic sinus did not rotate along the long-axis in anterior
      transposition of the great arteries, thus making the left-hand sinus, the lowest
      of this group, vulnerable to the high takeoff of the coronary arteries in
      anterior transposition of the great arteries.

PMID- 8874942
TI  - Five year trends in cardiac catheterization: a report from the Registry of the
      Society for Cardiac Angiography and Interventions.
AB  - The Society for Cardiac Angiography and Interventions has maintained a registry
      of cardiac catheterizations since 1979 and of percutaneous cardiac interventions
      since 1990. Data from 392,923 procedures (317,592 diagnostic catheterizations,
      74,963 coronary interventions, and 368 valvuloplasties) for the years 1990-1994
      inclusive are presented. Over the 5 year period there was a trend toward same day
      and 23 hr discharges (19% in 1990 to 29% in 1994), and a decrease in combined
      right and left heart procedures from 38% to 26%. For cardiac catheterizations
      ionic contrast use declined from 26% of procedures to 13% in 1994. The use of
      ionic contrast was even lower in interventional procedures, with laboratories
      reporting use in 21% of procedures in 1990 dropping to 9% in 1994. Balloons were
      the first choice device in 92.5% of native arteries and 82.7% of grafts in 1994.
      For the first time in 1994 more mitral than aortic valvuloplasties were reported.

PMID- 8874943
TI  - Implantation of balloon-expandable stents for coarctation of the aorta:
      implantation data and short-term results.
AB  - We report the immediate results and the short-term follow-up in a group of
      selected patients with coarctation of the aorta who underwent endovascular stent
      implantation. Balloon-expandable stents were implanted in 6 patients (mean age
      19.8 +/- 5.1 years) with coarctation of the aorta (4 recurrent and 2 native) who
      underwent a total of 7 procedures (6 implantation and 1 further expansion). The
      systolic peak pressure gradient was decreased from 36.7 +/- 16.9 to 13.3 +/- 23.2
      mm Hg (P < 0.005). There was a 66% increase in the mean coarctation diameter from
      9.3 +/- 1.7 to 15.6 +/- 3.1 mm (P = 0.001) with the ratio of the coarctation to
      descending aorta diameter, measured at the level of the diaphragm, increasing
      from 0.49 +/- 0.1 to 0.81 +/- 0.2 (P < 0.005). The dilatation was successful in
      expanding the stent to an acceptable diameter in 5 of 6 patients. One patient
      underwent successful further expansion of a stent implanted 22 months previously.
      There were no immediate complications during balloon expansion and stent
      implantation. One patient suffered a femoral arterial bleed requiring surgical
      repair. There was one unrelated death. All patients were hypertensive (systolic
      blood pressure > 140 mm Hg) prior to stent implantation. At mean follow-up of 8
      months, 3 patients are normotensive. There was no recurrence of coarctation,
      aortic dissection, or aneurysm formation in the patients in whom stent
      implantation was successful. These findings indicate that balloon-expandable
      stent implantation for coarctation of the aorta in selected patients is a safe
      and effective alternative approach for relieving the obstruction with a low
      complication rate and no recoarctation at short-term follow-up.

PMID- 8874944
TI  - Stenting coarctation of the aorta: promising concept but primitive technology.

PMID- 8874945
TI  - Percutaneous closure of small patent ductus arteriosus: comparison of Rashkind
      double-umbrella device and occluding spring coils.
AB  - We compared our current practice of closing small patent ductus arteriosus (PDA)
      with coils with our previous experience of using double-umbrellas. Twelve
      patients underwent percutaneous closure of a small PDA with a coil. Selection
      criteria were a minimal diameter of < or = 2.5 mm and angiographic type A or E.
      The 12 most recent, non-consecutive patients who had undergone double-umbrella
      device closure of a PDA and would presently be considered suitable candidates for
      spring coil occlusion were retrospectively reviewed. The two groups were compared
      with regard to complications and immediate and midterm results. Eleven of the 12
      attempted PDA occlusions using spring coils were successful. The mean follow-up
      period was 5.8 +/- 4.6 months. Color-Doppler echocardiograms have shown no
      residual leaks, no turbulence in the descending aorta, and no left pulmonary
      artery stenosis. All 12 attempted double-umbrella device placements were
      successful. The mean follow-up period was 16.2 +/- 5.8 months. Color-Doppler
      echocardiograms have shown trivial residual leaks in four patients and mild
      turbulent flow in the left pulmonary artery in one patient. There was no
      significant difference between the two groups in demographic and hemodynamic
      data. Although the mean follow-up time was significantly longer in the patients
      who underwent double-umbrella closure, there was significantly more color-Doppler
      echocardiographic evidence of residual flow (P < 0.03). Small PDA closure with
      coils is effective, resulting in less residual leaks compared with the double
      umbrella device.

PMID- 8874946
TI  - Which method to use for transcatheter occlusion of patent ductus arteriosus?

PMID- 8874947
TI  - Coil occlusion of a residual ductus arteriosus remaining after implantation of a
      buttoned device.
AB  - A 20-mo-old boy presented with persistence of significant shunt 13 mo after
      patent ductus arteriosus closure using the Sideris buttoned device. This residual
      shunt through the ductus arteriosus was successfully occluded using a Gianturco
      coil.

PMID- 8874948
TI  - Management of pediatric patients with isolated valvar aortic stenosis by balloon
      aortic valvuloplasty.
AB  - Moderate to severe aortic stenosis in children requires an initial procedure to
      improve the stenosis and often additional procedures for recurrent stenosis or
      aortic insufficiency before adulthood. The purpose of this study was to evaluate
      children who underwent balloon valvuloplasty and were followed with a specific
      management plan. Twenty-two children with aortic stenosis underwent balloon
      valvuloplasty and were followed on a regular basis. Repeat valvuloplasty was
      performed if indicated. The initial gradient was reduced from 63 +/- 9 mmHg to 28
      +/- 8 mmHg (P < 0.001). There were no deaths and only one major complication,
      which had no sequelae. Average follow-up was 61 +/- 23 months. Three patients
      required valve replacement 39-76 months after valvuloplasty for progressive
      insufficiency. Seven patients underwent successful repeat valvuloplasty. The
      overall probability of survival without surgical intervention was 75% at 100
      months. Balloon valvuloplasty is an effective intermediate palliation for aortic
      stenosis and is an acceptable alternative to surgical valvotomy. Repeat
      valvuloplasty is successful without additional risk. In a subgroup of patients,
      aortic insufficiency is progressive and will require surgical intervention.

PMID- 8874949
TI  - Acute myocardial infarction with dynamic outflow obstruction precipitated by
      intra-aortic balloon counterpulsation.
AB  - Dynamic left ventricular outflow obstruction is associated with structural
      findings of asymmetric septal hypertrophy (less commonly concentric left
      ventricular hypertrophy) and systolic anterior motion of the anterior mitral
      valve leaflet. A patient who did not have this usual substrate for outflow
      obstruction presented with an acute anterior wall myocardial infarction
      complicated by congestive heart failure and cardiogenic shock. When an intra
      aortic balloon pump was placed, the patient rapidly deteriorated and a dynamic
      outflow gradient was detected.

PMID- 8874950
TI  - Anomalous right coronary artery from the left sinus of Valsalva: demonstration of
      extensive collateral circulation.
AB  - Anomalous right coronary artery from the left coronary sinus was associated with
      inferior wall ischemia. There were extensive left-to-right collaterals. This is
      the first documentation of collateral circulation in this anomaly, extending its
      pathophysiologic spectrum to include this response to ischemia that is well-known
      in atherosclerotic disease.

PMID- 8874951
TI  - Aortic coarctation: a rare and unexpected cause of secondary arterial
      hypertension in the elderly.
AB  - We present a 72-year-old man with long-standing moderate hypertension, due to an
      aortic coarctation, who presented with a myocardial infarction. In view of his
      advanced age the aortic coarctation was treated conservatively.

PMID- 8874952
TI  - Giant coronary artery aneurysms and myocardial infarction in a patient with
      systemic lupus erythematosus.
AB  - A 26-year-old woman with systemic lupus erythematosus and end-stage renal disease
      presented for renal transplantation. She had no findings of cardiac disease.
      Radiologic evaluation, cardiac magnetic resonance imaging, and coronary
      angiography showed giant aneurysms of the right and left anterior descending
      coronary arteries. Despite therapy, acute anterior myocardial infarction
      developed during follow-up. Giant coronary artery aneurysms associated with
      systemic lupus erythematosus are unusual and their management is controversial.
      Antithrombotic therapy probably should be considered for giant coronary artery
      aneurysms.

PMID- 8874953
TI  - Fistulous connection between the left pulmonary artery and the innominate vein.
AB  - A 66-yr-old woman was admitted to our clinic with signs and symptoms suggesting
      either pulmonary embolism or pneumonia. Subsequently she was diagnosed as having
      pneumonia, but since pulmonary artery pressure was high on echocardiography,
      pulmonary angiography was performed to exclude the possibility of pulmonary
      embolism. No findings suggestive of pulmonary embolism were evident on pulmonary
      angiogram, but there was a fistulous connection between the left pulmonary artery
      and the innominate vein. To our knowledge, this report represents the first case
      of a fistula between the pulmonary artery and a systemic vein.

PMID- 8874954
TI  - Percutaneous mitral valvuloplasty with the Inoue technique in a patient with
      heavily calcified interatrial septum.
AB  - A 75-year-old woman with severe rheumatic mitral stenosis was admitted for
      percutaneous mitral valvuloplasty. Two-dimensional echocardiography disclosed
      severe calcification of the posterolateral left atrial wall and interatrial
      septum. Percutaneous mitral valvuloplasty, using the inoue technique, was
      successfully performed after a transseptal puncture through the calcified
      interatrial septum, avoiding the need for surgical intervention.

PMID- 8874955
TI  - Specifics of technique in percutaneous mitral commissurotomy in a case of
      dextrocardia and situs inversus with mitral stenosis.
AB  - Percutaneous mitral commissurotomy (PMC) was successfully performed in a 48-year
      old woman with dextrocardia and situs inversus and a severe mitral stenosis.
      After PMC, the valve area increased from 0.97 to 1.89 cm2, and no complication
      occurred. This case shows that PMC is practicable in a case of dextrocardia with
      situs inversus. The procedure appears to be safer and easier when carried out
      with the inoue balloon, image inversion on the screen, and under transesophageal
      echocardiographic monitoring.

PMID- 8874956
TI  - Safety and effectiveness of the Arani curve guiding catheters in Palmaz-Schatz
      stenting of right coronary artery stenosis.
AB  - The purpose of this study was to evaluate the safety and efficacy of Arani curve
      guiding catheters in Palmaz-Schatz stenting of right coronary artery (RCA)
      stenosis. A total of 15 stents was implanted in 13 right coronary arteries. For
      stenting of the RCA with marked superior orientation and shepherd's crook
      configuration of the proximal segment, a catheter with a 75 degrees primary curve
      was used. A catheter with a 90 degrees primary curve was usually the best choice
      for stenting of the RCA with slight superior, horizontal, or interior orientation
      of the proximal segment. These catheters provided excellent support in 12 of 13
      cases (93%) and resulted in successful stent deployment in these patients. There
      was one dissection which occurred distal to the stent following poststent balloon
      dilatation, and which required emergency coronary artery bypass graft surgery.
      There were no complications attributed to these guiding catheters. An
      extraordinary formation of pseudostenosis occurred in one patient. We conclude
      that Arani curve guiding catheters provide strong support and are safe and
      effective in stenting of RCA stenosis.

PMID- 8874957
TI  - Risks and benefits of the Arani curve guiding catheter for stenting of the right
      coronary artery: the value of experience.

PMID- 8874958
TI  - Clinical evaluation of a microsample coagulation analyzer, and comparison with
      existing techniques.
AB  - A new microsample coagulation analyzer (Hemochron Jr.) has recently been
      developed which performs a modified activated clotting time (ACT+) and an aPTT by
      using different reagents. The Hemochron Jr. measures the clotting time of a 5
      microliter whole-blood sample by an optical detector and extrapolates the results
      to the activated clotting time (ACT+) or the plasma-activated partial
      thromboplastin time by using a validated regression analysis. We compared 124
      simultaneous ACT+ and Hemochron ACTs, and 53 paired Hemochron Jr. aPTTs and
      hospital laboratory aPTTs, in 44 patients during coronary intervention. The
      Hemochron Jr. aPTT closely correlated with the lab aPTT (r = .79, P < .0001), and
      the test results were available much more rapidly than the lab aPTT (3.5 +/- 1.1
      vs. 56.3 +/- 25.5 min, P = 0.0029). A comparison of duplicate ACT+ measurements
      did not identify a significant difference in the means (292 +/- 115 sec vs. 293
      +/- 112 sec, P = 0.72). The ACT+ closely correlated with the Hemochron ACTs (r =
      .85, P < .0001). At baseline, the mean ACT+ (175 +/- 43 sec) exceeded the
      Hemochron ACT (144 +/- 36 sec) by 22% (P < .001). After heparin administration,
      the mean ACT+ (378 +/- 74 sec) exceeded the Hemochron ACT (332 +/- 65) by 12% (P
      < .001). The Hemochron Jr. provides a fast and reproducible methodology for
      measuring ACT and aPTT, using a small blood volume. Further studies are required
      to determine the optimal anticoagulation range when using the Hemochron Jr.
      during or after interventional procedures.

PMID- 8874959
TI  - Successful repair of intimal dissection following coronary angioplasty with a 48
      hour inflation of spiral inflation coil and local delivery of heparin.
AB  - We report on an unusual patient with a threatened occlusive dissection, in whom
      prolonged (48-hr) inflation of a balloon catheter with localized heparin infusion
      proved successful. This intracoronary infusion catheter maintained distal
      coronary flow on a unique spiral coil design, and may provide an alternative or a
      bridge to emergency operation or stent implantation.

PMID- 8874960
TI  - Facilitated advancement of the Palmaz-Schatz stent delivery system with the use
      of an adjacent 0.018" stiff wire.
AB  - The 5.0 French Palmaz-Schatz stent delivery system is a relatively bulky, stiff
      system which can be advanced only over a 0.014" wire. Although crossing failure
      is rare, advancement of the delivery system through tortuous, rigid vessels may
      be unsuccessful. We report on four consecutive cases in which the initial
      advancement of the Palmaz-Schatz stent delivery system was unsuccessful due to
      vessel tortuosity or vessel angulation. The use of a 0.018" stiff wirer adjacent
      to the Palmaz-Schatz delivery system, to "straighten" the vessels and to give
      additional guide catheter support, allowed for the successful advancement and
      delivery of coronary stents in all four cases.

PMID- 8874961
TI  - Innovative use of a long sheath for removal of a knotted pacing electrode.

PMID- 8874962
TI  - L1, N-cadherin, and laminin induce distinct distribution patterns of cytoskeletal
      elements in growth cones.
AB  - Growth cones are highly motile extensions of growing neuronal processes that have
      a well-characterized cytoskeleton, which is necessary for motility and directed
      growth. In culture, neurons have been observed to extend processes on a variety
      of substrates made of cell adhesion molecules (CAMs) or extracellular matrix
      molecules (ECM molecules). We have previously shown that retinal ganglion cell
      (RGC) growth cones exhibit characteristic morphologies dependent on the substrate
      on which they are grown (Payne et al., 1992: Cell Motil. Cytoskel. 21:65-73).
      Upon contact with a sharp border between two substrates, the growth cones display
      rapid changes in morphology (Burden-Gulley et al., 1995: J. Neurosci. 15:4370
      4381) that may result from extensive restructuring of the cytoskeleton. In the
      present study, immunocytochemical methods were used to examine the distribution
      of three cytoskeletal elements in RGC growth cones growing on L1, N-cadherin, or
      laminin as well as on dishes coated with alternating lanes of these substrates.
      Distinct distribution patterns of f-actin, microtubules (MTs), and neurofilaments
      (NFs) were observed in growth cones growing on individual substrates. At border
      regions between two substrates, growth cones with extensive lamellipodial contact
      with the second substrate were observed to have f-actin and MT distribution
      patterns appropriate for the new substrate encountered. Contact via filopodia
      alone did not evoke this change. Redistribution of NFs was observed only after
      the majority of the growth cone had crossed onto the second substrate. These
      results suggest that actin and MTs, but probably not NFs, are directly influenced
      by CAMs and ECM molecules to produce changes in growth cone morphology. The
      distribution of two members of the protein tyrosine kinase family, pp60arc and
      p59fyn, and phosphorylated tyrosine residues was also examined. No differences
      were observed in the distribution patterns of the kinases and phosphorylated
      tyrosine residues in growth cones on any of the substrate molecules tested. In
      addition, the distribution patterns were unchanged in growth cones that contacted
      and crossed borders between two substrates. These results suggest that
      redistribution of pp60arc or p59fyn is not required to produce alterations in
      growth cone morphology induced by contact with L1, N-cadherin or laminin.

PMID- 8874963
TI  - Stimulation of microtubule dynamic turnover in living cells treated with okadaic
      acid.
AB  - We have examined the effects of okadaic acid, an inhibitor of protein
      phosphatases type 1 and 2A, on the dynamic instability behavior of individual
      microtubules in living cells. Addition of 1 microM okadaic acid to PtK1
      epithelial cells induced ruffling of lamellar regions; after 50 min in okadaic
      acid, many cells were observed to round up. Confocal microscopy of okadaic acid
      treated cells stained with an antibody to tubulin showed that microtubules were
      more densely packed near the periphery of the rounded cells, and in many cells, a
      reduction in the density of microtubules near the microtubule-organizing center
      was observed. The dynamic behavior of individual microtubules in cells previously
      injected with rhodamine-labeled tubulin was quantified by tracking individual
      microtubules from image sequences. Microtubule dynamic turnover was markedly
      stimulated in cells treated with 1 microM okadaic acid for 50-60 min: The average
      rates of both microtubule growing and shortening increased, and the average
      duration of pause, or attenuation, a phase in which neither growth nor shortening
      could be detected, was significantly decreased. Further, okadaic acid induced an
      approximately twofold increase in the frequency of catastrophe transitions and a
      threefold decrease in the frequency of rescue transitions. Dynamicity, a measure
      of the net gain and loss of polymer at microtubule plus ends, increased nearly
      threefold in okadaic acid-treated cells. These results demonstrate that
      microtubule turnover is stimulated in okadaic acid-treated cells and suggest that
      phosphorylation of molecules which interact with microtubules may result in
      increased microtubule dynamic turnover in vivo.

PMID- 8874964
TI  - Actin-based vesicle dynamics and exocytosis during wound wall formation in
      characean internodal cells.
AB  - Characean internodal cells readily form wound walls upon local membrane damage.
      In the present study we documented the dynamics of vesicles involved in wound
      wall secretion and compared them with actin organization in equivalent cells
      using immunofluorescence. Single exocytotic events (spreading of vesicle
      contents) could be visualized using image enhancement by video microscopy. In
      control unwounded cells vesicles moved unidirectionally along parallel actin
      bundles and rarely contacted the plasma membrane. The wound response started with
      (1) local inhibition of active cytoplasmic streaming (unidirectional movements)
      due to inactivation, depolymerization, or mechanical displacement of the
      subcortical actin bundles. Accordingly, vesicles performed only oscillating
      motions and moved slowly with the same velocity and direction as passive
      endoplasmic flow. (2) Several minutes after wounding, vesicles started to perform
      random saltatory movements with frequently changing velocities, punctuated by
      oscillating motion and periods of immobility (docking) at the plasma membrane.
      Vesicle trajectories correlated with a fine-meshed actin network at the wound
      site. (3) Several hours after wounding, vesicles moved again unidirectionally
      along regenerated subcortical actin bundles. Spreading of vesicles (vesicle
      contents) was observed during wound wall formation, i.e., during the period of
      saltatory movements when vesicles had access to the plasma membrane. Dependent on
      the type of wound wall being secreted, three variants could be distinguished: (1)
      slow and continuous spreading over a time period of several seconds up to 30 min
      near the plasma membrane, (2) fast spreading within 80 ms inside an already
      formed wound wall, and/or (3) fast spreading at the plasma membrane. We conclude
      from our study that wounding-induced changes in vesicle dynamics are due to
      transient reorganization of the actin cytoskeleton from parallel bundles to a
      fine-meshed network. Furthermore, our results indicate that spreading of vesicle
      contents varies considerably with time and may be delayed by vesicle docking
      and/or discharge.

PMID- 8874965
TI  - Differential expression of tubulin isotypes during the cell cycle.
AB  - Microtubules play an essential role in cell division. Little is known about
      possible variations of total tubulin and tubulin isotype expression during the
      cell cycle. We analyzed the total tubulin content, tubulin polymerization status
      and tubulin isotype content in resting and dividing human K562 leukemic cells and
      human MES-SA sarcoma cells. Although the total cellular tubulin content increases
      as the cells progress toward mitosis, the total tubulin/total protein ratio is
      stable during the cell cycle. Reverse transcriptase-polymerase chain reaction was
      applied to analyze the levels of expression of alpha, beta, and gamma-tubulin
      isotypes. Whereas alpha-tubulin isotype and gamma-tubulin transcripts were found
      to be expressed at constant levels throughout the cell cycle, some of the beta
      tubulin isotype transcripts were found to be more highly expressed in dividing
      then in resting cells. Both of the class IV beta-tubulin isotype transcripts
      (human 5 beta and beta 2, Class IVa and IVb, respectively) were expressed in
      dividing K562 and MES-SA cells at twice the levels found in resting cells.
      Increased expression of the class IV isotype proteins in dividing cells was
      confirmed by immunoblotting, both in K562 and in MES-SA cells. A larger fraction
      of total cell tubulin was found to be polymerized in dividing cells (36-40%) than
      in resting cells (27-30%). The degree of polymerization of class IV tubulin in
      dividing and resting cells was similar to that of total tubulin. These results
      show that total tubulin is expressed as constant levels throughout the cell cycle
      but that the degree of polymerization is increased as cells are committed to
      division. The relative overexpression of the two class IV beta-tubulin isotypes
      in dividing cells suggests functional specificity for these isotypes and a
      regulatory role of these isotypes on the microtubule network during mitosis.

PMID- 8874966
TI  - Dictyostelium cell shape generation requires myosin II.
AB  - Myosin II function has been implicated in non-muscle cell behaviors including
      movement, cytokinesis, and multicellular morphogenesis. Surprisingly, two
      dimensional morphology and behavior of Dictyostelium amoebae lacking myosin II
      (mhcA-) is not dramatically altered when cells are examined using conventional
      imaging techniques. We have observed amoebae from the side (side-view microscopy
      or SVM) and find that wild-type but not mhcA- cells undergo extensive three
      dimensional (3D) shape changes. These shape changes often occur above the plane
      of the substrate and are morphologically distinct from pseudopods. For example,
      unlike pseudopods, vertically extended cell regions are not enriched in F-actin
      and do not exclude organelles. In contrast, mhcA- cells generate F-actin-filled
      pseudopods and spread laterally but do not undergo vertical extension. When wild
      type cells are removed from the substrate and shaken in suspension, they retain
      their irregular three-dimensional shape. Suspended mhcA- cells, however, rapidly
      become spherical. Thus, cells lacking myosin appear to be incapable of generating
      or maintaining 3D shape independent of a substrate. When a substrate is
      available, these cells can attach and spread on the surface in a myosin
      independent manner. These previously undescribed defects of mhcA- cells reveal
      that 3D cell shape generation requires myosin II and is mechanistically distinct
      from pseudopod formation.

PMID- 8874967
TI  - Microfilament-membrane interactions in Xenopus myocytes.
AB  - We used quick-freeze, deep-etch, rotary-replication transmission electron
      microscopy to determine at molecular resolution the organization of
      microfilaments at the cytoplasmic surface of the sarcolemma of Xenopus myocytes.
      We demonstrate that actin microfilaments interact with the sarcolemma in two
      distinct ways. In one, which resembled focal contacts in Xenopus fibroblasts
      [Samuelsson et al., 1993: J. Cell Biol. 122:485-496], bundles of microfilaments
      approached the sarcolemma at sites containing aggregates of membrane-associated
      particles. Immunogold cytochemistry showed that these particle aggregates
      contained vinculin, talin and beta 1-integrin. In the second, which covered most
      of the cytoplasmic surface of the sarcolemma, individual actin microfilaments
      formed an extensive, lattice-like array. Particle aggregates associated with this
      array of actin microfilaments also labeled with antibodies to vinculin, talin and
      beta 1-integrin. The unique, lattice-like association of actin microfilaments
      with the membrane in Xenopus myocytes suggests that the organization of actin
      filaments over most of the sarcolemma is distinct from focal contacts, mediating
      widespread associations of the actin cytoskeleton with the cytoplasmic membrane
      face.

PMID- 8874968
TI  - Activity of east African medicinal plants against Helicobacter pylori.
AB  - The activity of extracts from the East African medicinal plants Entada abyssinica
      (stem bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots),
      Ximenia caffra (roots), Azadirachta indica (leaves and stem bark) and Spilanthes
      mauritiana (roots and flowers) were evaluated against 12 strains of Helicobacter
      pylori. The most active extracts were those derived from T. spinosa with an MIC50
      of 125 micrograms/ml, an MIC90 of 250 micrograms/ml and an MIC range of 62.5-500
      micrograms/ml. An MIC50 of 250 micrograms/ml and an MIC90 of > 4,000
      micrograms/ml was reached by H. abyssinica with a range of 125-->4,000
      micrograms/ml and by X. caffra with a range of 62.5-->4,000 micrograms/ml,
      respectively. It is concluded that these plants contain compounds with
      antimicrobial activity against H. pylori.

PMID- 8874969
TI  - In vitro susceptibility studies of Plasmodium falciparum isolates and clones
      against type II antifolate drugs.
AB  - Six clones were derived from each Plasmodium falciparum isolate obtained from
      Malaysia, Africa and Thailand and were characterized against type II antifolate
      drugs, cycloguanil and pyrimethamine using the modified in vitro microtechnique.
      Results showed that these isolates were of a heterogeneous population, with 50%
      inhibitory concentrations of Gombak A clones at 0.0151-0.1450 and 0.0068-0.1158
      microM, Gambian clones at 0.0056-0.1792 and 0.0004-0.0068 microM and TGR clones
      at 0.0103-0.0703 and 0.0776-0.3205 microM against cycloguanil and pyrimethamine,
      respectively. All clones displayed similar susceptibilities as their parent
      isolates except A/D3, A/D5, A/G4 and A/H7 clones which were sensitive to
      cycloguanil at 0.0735, 0.0151, 0.0540 and 0.0254 microM but Gm/B2 clone was
      resistant at 0.1792 microM, respectively. However, A/D3, TGR/B4, TGR/B7, TGR/C4,
      TGR/C7 and TGR/H2 clones were resistant to pyrimethamine at 0.1158, 0.1070,
      0.1632, 0.1580, 0.2409 and 0.3205 microM, respectively. Further results indicated
      that they were pure clones compared to their parent isolates as their drug
      susceptibility studies were statistically different (p < 0.05).

PMID- 8874970
TI  - In vitro activity of cefetamet against enterobacteria expressing an SHV-5-type
      beta-lactamase.
AB  - The in vitro activity of cefetamet against Escherichia coli, Klebsiella
      pneumoniae and Serratia marcescens strains expressing an SHV-5-type beta
      lactamase was evaluated. Most of the examined strains were susceptible to the
      antibiotic. Cefetamet was found to be considerably more active than ceftazidime
      and aztreonam. Its activity was comparable to that of cefotaxime. Cefetamet MIC
      values were related to the quantity of the enzyme expressed. The SHV-5-type
      enzyme hydrolysed cefetamet with an efficiency (Vmax/Km) similar to that of
      ceftazidime.

PMID- 8874971
TI  - Distribution of a methicillin-resistance gene in urinary isolates of methicillin
      resistant staphylococci examined by enzymatic detection of the polymerase chain
      reaction.
AB  - We tried to examine the susceptibility to various antimicrobial agents and to
      detect the mec A gene using enzymatic detection of the polymerase chain reaction
      in methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive
      Staphylococcus aureus (MSSA) and Staphylococcus epidermidis isolated from
      patients with complicated urinary tract infections (UTIs). All the strains of
      MRSA and MSSA showed a low sensitivity to imipenem (IPM), ceftazidime (CAZ),
      flomoxef (FMOX), amikacin (AMK), ciprofloxacin (CPFX) and ofloxacin (OFLX).
      Although all the strains of MRSA had the mec A gene, none of the MSSA strains had
      it. 74% of S. epidermidis had the mec A gene and strains resistant to methicillin
      were seen in 72% of them. The mec A-positive S. epidermidis showed a lower
      susceptibility to IPM, CAZ, FMOX, AMK, CPFX and OFLX than the mec A-negative
      strains. These results suggest that methicillin resistance was due to the mec A
      gene in MRSA and methicillin-resistant S. epidermidis (MRSE), and that MRSEs were
      very common among the bacteria causing complicated UTI. When we try to control
      nosocomial infections due to MRSA, it should also be noted that MRSE can be a
      reservoir of the mec A gene.

PMID- 8874972
TI  - Susceptibility of clinical isolates to expanded-spectrum beta-lactams alone and
      in the presence of beta-lactamase inhibitors.
AB  - Tazobactam and BRL 42715 are relatively new penems which inhibit a wide range of
      plasmid- as well as chromosomally mediated bacterial beta-lactamases that include
      Richmond and Sykes type I, II, III, IV and V beta-lactamases, staphylococcal
      penicillins and extended-spectrum beta-lactamases. However, clavulanic acid,
      which is a potent inhibitor of class III beta-lactamases, is one of the first
      discovered compounds. We used a total of 645 recent clinical isolates, consisting
      of 305 Enterobacteriaceae, 180 gram-positive cocci and 160 other gram-negative
      bacteria to evaluate the ability of beta-lactamase inhibitors for potentiation of
      piperacillin, ticarcillin and amoxycillin. Minimum inhibitory concentrations for
      all the 42 strains of methicillin-susceptible Staphylococcus aureus were reduced
      4- to 16-fold in the presence of beta-lactamase inhibitors. They were also highly
      effective in inhibiting the beta-lactamase of a wide variety of gram-negative
      bacteria, thereby changing their MIC values for amoxycillin, ticarcillin and
      piperacillin from a 'resistant' to a 'susceptible' range. Commonly resistant
      bacteria like Klebsiella, Enterobacter, Serratia, Acinetobacter and Pseudomonas
      were rendered susceptible to piperacillin and ticarcillin in the presence of
      clavulanic acid, tazobactam and BRL 42715. Of the commercially available
      formulations for clinical use, piperacillin/tazobactam (Tazocin) was found to be
      more inhibitory towards both gram-positive and gram-negative bacteria.

PMID- 8874973
TI  - Antagonism of teicoplanin and vancomycin activity by chocolatized Mueller-Hinton
      agar.
AB  - Chocolatized (80 degrees C, 13 min) Mueller-Hinton agar antagonized the
      inhibitory activities of teicoplanin and vancomycin against reference strains of
      Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae,
      Staphylococcus aureus, and Enterococcus faecalis. This antagonism was due to heat
      exposed sheep erythrocytes, sheep hemoglobin, and the supernatant fluid from
      lysed sheep erythrocytes, but not to sheep serum. Neither water-soluble
      cholesterol, bovine albumin, bovine serum, hematin, hemin nor egg yolk suspension
      antagonized teicoplanin and vancomycin.

PMID- 8874974
TI  - Survey of antibiotic susceptibility among gram-negative bacilli at a cancer
      center.
AB  - A survey of the susceptibility of gram-negative bacilli isolated from cancer
      patients to broad-spectrum antimicrobial agents was conducted. The organisms were
      isolated from all patient specimens submitted to the microbiology laboratory
      during a 3-month study period. Overall, the least resistance was observed against
      cefoperazone/sulbactam, ciprofloxacin, and imipenem. Of these,
      cefoperazone/sulbactam has had limited usage at our institution. Drugs used more
      frequently (piperacillin, aztreonam, cefoperazone, ceftazidime) were associated
      with greater levels of resistance. Imipenem and ciprofloxacin have enjoyed wide
      usage but the level of resistance remains low.

PMID- 8874975
TI  - Pharmacodynamic effects of ciprofloxacin, fleroxacin and lomefloxacin in vivo and
      in vitro.
AB  - The present study investigates the postantibiotic effect (PAE) in vivo, and the
      postantibiotic subinhibitory concentration effects (PA-SE) in vitro and SE in
      vivo of three 4-fluoroquinolones (ciprofloxacin, fleroxacin and lomefloxacin)
      against standard strains of Staphylococcus aureus and Escherichia coli. In vivo
      killing kinetics have also been performed using two different short
      administrations to study if the PAE duration could cover the time that the
      antibiotic was below the minimal inhibitory concentration (MIC) in serum. The
      results show that the three antimicrobial agents induced long PAEs (1.9-3.1 h)
      against the two microorganisms. Moderate but significant in vitro PA-SEs were
      also produced (1-->9 h). The in vivo SEs were not significant except when the
      effect of lomefloxacin on E. coli was assayed (0.54 h). Finally, the in vivo
      killing kinetics showed that the administrations that included the PAE duration
      were as effective as the schedule that maintained the antibiotic levels in serum
      above the MIC. Only when fleroxacin and S. aureus were assayed, this last
      administration was more effective (+0.9 log10 colony-forming units/thigh).

PMID- 8874976
TI  - Role of bacterial biofilms in the chemotherapy of cholangitis with brown pigment
      stones.
AB  - The purpose of the present study was to clarify the role of biofilms in the
      chemotherapy of cholangitis. In 1 case of recurrent cholangitis with intrahepatic
      stones, the patient underwent right hepatectomy after chemotherapy was performed
      for 42 weeks. In the other case, chemotherapy including ciprofloxacin was
      performed during an attack of recurrent cholangitis. Repeated culture of bile
      specimens yielded negative results, whereas culture of the choledochal stone
      yielded Pseudomonas aeruginosa. We observed an acute transient IgM response to a
      component of the biofilm of P. aeruginosa (alginate) in this case. In both cases,
      electron microscopy revealed viable bacteria covered with biofilm in the
      component of brown pigment stones. It was concluded that biofilm is a factor of
      drug resistance.

PMID- 8874977
TI  - Comparison of itraconazole and ketoconazole in HIV-positive patients with
      oropharyngeal or esophageal candidiasis. Human Immunodeficiency Virus
      Itraconazole Ketoconazole Project Group.
AB  - The efficacy of oral itraconazole and ketoconazole in the treatment of
      oropharyngeal and/or esophageal candidiasis, and the rate of post-treatment
      relapse, were compared in a multicenter, prospective, double-blind, double-dummy,
      randomized, parallel-group trial. A total of 143 adult HIV-positive patients with
      oropharyngeal and/or esophageal candidiasis were assigned to receive either
      itraconazole or ketoconazole (200 mg/day). Patients with oropharyngeal and
      esophageal candidiasis were treated for 2 and 4 weeks, respectively. Patients
      were evaluated clinically and mycologically after 1, 2 and 4 (for esophageal
      patients) weeks of therapy, and relapses were compared in a 6-week post-treatment
      follow-up period. Of 129 evaluable patients, 98 had oropharyngeal candidiasis and
      31 esophageal infection. CDC classification, CD4+ cell counts, and number of
      previous episodes of oropharyngeal or esophageal candidiasis were comparable in
      both groups. Oropharyngeal infection was cleared clinically at 21 days in 71% of
      patients receiving itraconazole and 60% receiving ketoconazole, and esophageal
      candidiasis was cleared at 41 days in 100% of patients receiving itraconazole and
      91% receiving ketoconazole. Marginally significant differences were found between
      itraconazole and ketoconazole in rates of clearing of infection clinically in
      patients with oropharyngeal and esophageal candidiasis (p = 0.0614 and 0.0781,
      respectively). Mean rates of infection relapse were not statistically different
      in the two treatment groups. Adverse events were generally mild and not
      considered drug related. Itraconazole is marginally more efficacious than
      ketoconazole in the treatment of oropharyngeal and esophageal candidiasis in HIV
      positive patients and both drugs appear safe and well tolerated.

PMID- 8874978
TI  - Antimicrobial prophylaxis with ceftriaxone in neurosurgical procedures. A
      prospective study of 100 patients undergoing shunt operations.
AB  - Shunt infection is a major complication of shunt implantation, with
      Staphylococcus epidermidis found in almost 45% of infected shunts. This pathogen
      produces an extracellular slime that enables it to adhere to implantable devices
      and resist antibiotic therapy. Antimicrobial prophylaxis can prevent slime
      production. In this paper we report the results of a prospective study involving
      100 shunt operations. The objective was to evaluate the efficacy of a single
      preoperative dose of ceftriaxone (2 g, i.v.) in preventing shunt infection.
      Ceftriaxone was chosen for its pharmacokinetic properties. No shunt infection was
      observed over a 4-year follow-up period. On the basis of these results we
      recommend prophylaxis with ceftriaxone as a safe and effective way of preventing
      shunt infection. In addition, one-shot prophylaxis with ceftriaxone is more cost
      effective than multiple-dose antibiotic regimens.

PMID- 8874979
TI  - Crab clockwork: the case for interactive circatidal and circadian oscillators
      controlling rhythmic locomotor activity of Carcinus maenas.
AB  - The circalunidian hypothesis that tidal rhythms in coastal animals are controlled
      by two lunar-day (c.24.8 h) oscillators coupled in antiphase is challenged.
      Rhythmic locomotor activity patterns of the shore crab Carcinus maenas, and
      probably of some other species too, are more economically explained by
      interacting circadian (c.24 h) and true circatidal (c.12.4 h) physiological
      oscillators. A testable hypothesis is proposed that combines a circadian promotor
      and a circatidal inhibitor of locomotor activity.

PMID- 8874980
TI  - Temporal variations of adenosine metabolism in human blood.
AB  - Eight diurnally active (06:00-23:00 h) subjects were adapted for 2 days to the
      room conditions where the experiments were performed. Blood sampling for
      adenosine metabolites and metabolizing enzymes was done hourly during the
      activity span and every 30 min during sleep. The results showed that adenosine
      and its catabolites (inosine, hypoxanthine, and uric acid), adenosine
      synthesizing (S-adenosylhomocysteine hydrolase and 5'-nucleotidase), degrading
      (adenosine deaminase) and nucleotide-forming (adenosine kinase) enzymes as well
      as adenine nucleotides (AMP, ADP, and ATP) undergo statistically significant
      fluctuations (ANOVA) during the 24 h. However, energy charge was invariable.
      Glucose and lactate chronograms were determined as metabolic indicators. The same
      data analyzed by the chi-square periodogram and Fourier series indicated
      ultradian oscillatory periods for all the metabolites and enzymatic activities
      determined, and 24-h oscillatory components for inosine, hypoxanthine, adenine
      nucleotides, glucose, and the activities of SAH-hydrolase, 5'-nucleotidase, and
      adenosine kinase. The single cosinor method showed significant oscillatory
      components exclusively for lactate. As a whole, these results suggest that
      adenosine metabolism may play a role as a biological oscillator coordinating
      and/or modulating the energy homeostasis and physiological status of erythrocytes
      in vivo and could be an important factor in the distribution of purine rings for
      the rest of the organism.

PMID- 8874981
TI  - The difference between activity when in bed and out of bed. II. Subjects on 27
      hour "days".
AB  - Nine healthy subjects have been studied while exposed to the normal alternation
      of light and dark, but with their sleep and activity pattern adjusted to a 27-h
      "day" for 17 imposed "days." Rectal temperature showed clearly the competing
      influences of 27-h and 24-h components, and these were separated by the method of
      "purification." The method indicated that the endogenous component had a constant
      amplitude throughout the experiment and remained entrained to solar (24-h) time;
      by contrast, the exogenous component followed the imposed 27-h "day" and
      increased rectal temperature in proportion to the amount of subjects' activity.
      Wrist movement was used to assess activity while in bed (attempting sleep) and
      out of bed (when naps were forbidden). While these results confirmed adherence of
      the subjects to the imposed 27-h "days," they also showed that the dichotomy
      between "out of bed" activity and "in bed" inactivity depended on the phase
      relationship between endogenous (24h) and exogenous (27h) components. Thus, the
      dichotomy was highest and was equal to that during control days (with a
      conventional 24-h life-style) when the two components were in phase and lowest
      when the solar and imposed day were in antiphase. This was due to changes in
      activity, both during time spent in bed and out of bed. We confirm that this
      protocol can produce valuable information about the properties of the circadian
      system in humans and the value of the process of purification of temperature
      data. We have established also that the very simple and noninvasive measurement
      of wrist movement, coupled with its use to calculate dichotomy indices, provides
      valuable information that both confirms and extends the results obtained from the
      more conventional (but also more invasive) measurement of rectal temperature.

PMID- 8874982
TI  - Delaying and extending sleep during weekends: sleep recovery or circadian effect?
AB  - There is a well-known tendency to delay and prolong our sleep during weekends
      (Saturday and Sunday), with an advance and reduction of sleep during workdays
      (Monday to Friday). The objective of this work was to determine if the changes of
      sleep during weekends are produced by a partial sleep deprivation or a lack of
      entraining of circadian rhythms to an advanced phase, during workdays. The
      subjects were 52 undergraduate female students, mean age = 17.5 years, SD = 1.32.
      All students attended school following a regular schedule, from Monday to Friday.
      Two groups of students were studied: one attended school from 07:00 to 12:00 h
      (morning group, n = 30); the other attended school from 14:00 to 18:00 (afternoon
      group, n = 22). None of the students worked or was engaged in other activity with
      a fixed schedule. All kept a sleep-wake diary for 2 weeks, in which they recorded
      their bedtimes, wakeup times, and sleep-onset latencies. The morning group
      delayed 47.4 min [t(29) = 4.72, p < 0.0001] and prolonged their sleep 118.2 min
      [t(29) = 9.4, p < 0.0001] during weekends. Although the afternoon group had the
      opportunity to maintain a delayed phase and a long sleep time throughout the
      week, they delayed their bedtime by 24 min [t(21) = 2.99, p < 0.01] during
      weekends, without changing their sleep duration. The findings suggest that the
      prolonged sleep during weekends is due to reduction of sleep during workdays,
      whereas the delay of bedtime seems to be associated with a tendency of the human
      circadian system to maintain a delayed phase with respect to the solar daylight
      period.

PMID- 8874984
TI  - Day-night differences in the kinetics and dynamics of insulin: diabetic versus
      normal Yucatan minipigs.
AB  - Time-dependent variations in the pharmacokinetics and pharmacodynamics of insulin
      were studied at two times, 10:30 and 20:30 during the same day in normal and
      streptozotocin (STZ)-induced diabetic minipigs housed in L(06:00):D(18:00) using
      the intravenous insulin tolerance test. Following intravenous insulin (0.1 IU/kg)
      administration in normal minipigs, the time for the glucose level to reach nadir
      (tnadir) was significantly longer in the evening than the morning [(A.M.; 30.4
      (+/- 2.4) vs. P.M.: 38.5 (+/- 3.3) min] (p < 0.01), although maximum reduction of
      glucose level (nadir) in the morning and evening was not significantly different
      [A.M.: (-70 (+/- 2) vs. P.M.: -65 (+/- 5) %]. The rate of glucose decline (Kin)
      was significantly decreased in the evening [A.M.: 5.33 (+/- 0.71) vs. P.M.: 4.44
      (+/- 0.54) %dBG/min] (p < 0.01), and the integrated glucose-lowering response
      (ABCB) was significantly higher in the evening than the morning [A.M.: 3.18 (+/-
      0.38) vs. P.M.: 4.52 (+/- 0.30) (g/dl)* min] (p < 0.01). The area under the
      plasma insulin concentration curve was increased significantly in the evening
      [A.M.: 2.26 (+/- 0.174) vs. P.M.: 2.74 (+/- 0.18) (mU/ml)* min], while the
      morning plasma insulin half-life did not differ significantly from that in the
      evening [A.M.: 4.79 (+/- 0.36) vs. P.M.: 5.47 (+/- 0.47) min]. After induction of
      diabetes by intravenous STZ injections, minipigs became diabetic, baseline blood
      glucose was observed to increase from the range of 45-55 to 200-250 mg/dl while
      plasma insulin levels decreased from 7-12 to 3-5 uU/ml. In the STZ-induced
      diabetic minipigs, a higher dose (0.2 IU/kg) was used in the intravenous insulin
      tolerance test in an attempt to normalize the high glucose levels. Following
      intravenous administration of insulin, the evening Kin and ABCB were
      significantly higher than they were in the morning [Kin = A.M.: 0.99 (+/- 0.25)
      vs. P.M.: 1.75 (+/- 0.44) %dBG/min (p < 0.01); ABCB = A.M.: 12.63 (+/- 1.91) vs.
      P.M.: 19.09 (+/- 5.43) (g/dl)* min (p < 0.01)]. However, there was no significant
      difference between tnadir and nadir values obtained in the morning and evening
      [tnadir = A.M.: 81.4 (+/- 9.2) vs. P.M.: 92.8 (+/- 13.7) min; nadir = A.M.: 39.6
      (+/- 5.2) vs P.M.: 48.0 (+/- 9.0) %]. The pharmacodynamics and pharmacokinetics
      of IV insulin both were found to be highly dose-dependent (r > 0.90).

PMID- 8874983
TI  - Oral contraceptives alter circadian rhythm parameters of cortisol, melatonin,
      blood pressure, heart rate, skin blood flow, transepidermal water loss, and skin
      amino acids of healthy young women.
AB  - Sixteen healthy women users and nonusers of oral contraceptives (OC) volunteered
      to document a set of circadian rhythms. Nine were taking OC providing ethynyl
      estradiol (0.03-0.05 mg/24h, 21 days/month) combined with DL- or L-norgestrel or
      norethisterone. There was no group difference (p > 0.05) in median age (22
      years), weight (57 kg), and height (162) cm). Data were obtained at fixed hours,
      5 times/24h, during a 48-h span, in November. (Day activity from approximately
      08:00 to approximately 23:00 h and night rest). Environmental conditions were
      controlled, using air-conditioned rooms of constant temperature (26 degrees +/-
      0.5) and relative humidity 45% +/- 1. Both cosinor and ANOVA were used for
      statistical analyses. All circadian rhythms were validated with one exception:
      that of salivary melatonin was not detected in OC users. The 24h mean (M)
      exhibited group differences for certain variables: M was greater in OC than non
      OC users for systolic blood pressure (p < 0.0001), heart rate (p < 0.01), skin
      blood flow (p < 0.04), and transepidermal water loss (p < 0.02). M was lower in
      OC than non-OC users in salivary cortisol (p < 0.04) and skin amino acids (p <
      0.003). No group difference was detected in any other documented rhythms:
      diastolic blood pressure, grip strength of both hands, oral temperature, self
      rated fatigue, and the skin variables of urea, lactate, triglycerides, and acid
      phosphatase activity.

PMID- 8874985
TI  - Temporal variation in the interaction between calcium channel blockers and
      morphine-induced analgesia.
AB  - Circadian variations in the interaction between calcium channel blockers and
      morphine-induced analgesia were determined by the mouse hot-plate test. Calcium
      channel blockers diltiazem, verapamil, or nicardipine alone did not display any
      significant analgesic effect, but all of them potentiated morphine-induced
      analgesia when injected 30 min prior to morphine at most of the injection times.
      In terms of percent absolute potentiation, they produced more potentiation during
      the light period than darkness. Their potentiating effects decreased abruptly
      during darkness, and around the midtime of the dark period no significant
      potentiation of morphine-induced analgesia was observed. It is concluded that
      these fluctuations in the magnitude of interaction between calcium channel
      blockers and morphine must be taken into consideration particularly in studies
      dealing with the role of calcium in analgesia.

PMID- 8874986
TI  - Monotherapy with HMG-CoA reductase inhibitors and secondary prevention in
      coronary artery disease.
AB  - Although thrombolytic drugs, percutaneous transluminal coronary angioplasty, and
      coronary artery bypass grafting have provided major advances in the treatment of
      coronary artery disease, the use of lipid-lowering drugs for secondary prevention
      has significantly reduced cardiovascular events in the population with coronary
      artery disease. Secondary prevention trials using HMG-CoA reductase inhibitors
      include the Familial Atherosclerosis Treatment Study (FATS), the Monitored
      Atherosclerosis Regression Study (MARS), the Canadian Coronary Atherosclerosis
      Intervention Trial (CCAIT), the Asymptomatic Carotid Artery Progression Study
      (ACAPS), the Multi Anti-Atheroma Study (MAAS), the Scandinavian Simvastatin
      Survival Study (4S), the Pravastatin Limitation of Atherosclerosis in Coronary
      Arteries (PLAC I), the Regression Growth Evaluation Statin Study (REGRESS), the
      Pravastatin Multinational Study, and the Pravastatin, Lipids, and Atherosclerosis
      in Carotids (PLAC II). Mean changes from baseline of lipid fractions in these
      trials included: total cholesterol 18 to 35% reduction; low-density lipoprotein
      (LDL) cholesterol 26 to 46% reduction; high-density lipoprotein (HDL) cholesterol
      5 to 15% increase; and triglyceride 7 to 22% reduction. Angiographic regression
      or lack of progression was statistically demonstrated in the FATS, MARS, CCAIT,
      MAAS, PLAC I, and REGRESS trials. Cardiovascular events decreased 25 to 92% in
      all trials, and there was a significant reduction in both cardiovascular and
      total mortality in the 4S. The greater reduction in cardiovascular events than in
      anatomic changes suggests that the HMG-CoA reductase inhibitors stabilized the
      surface of plaques. Monotherapy with HMG-CoA reductase inhibitors provides the
      clinical opportunity to modify the natural history of coronary artery disease.

PMID- 8874987
TI  - Systemic side effects of topical beta-adrenergic blockers.
AB  - Glaucoma, a disease that affects between 1 and 3% of the population above the age
      of 60, is most commonly treated by topical beta-adrenergic blockers. Although
      effective in lowering intraocular pressure and helping to preserve sight, beta
      blockers also may have adverse influences on the cardiac, pulmonary, and central
      nervous systems, and on endocrine functions. Clinicians' awareness that their
      patients may be treated with topical beta blockers will help them to elicit this
      information and the history, prescribe the medicine correctly, and be cognizant
      of a possible role this medicine may have in any deterioration of a patient's
      systemic clinical status.

PMID- 8874988
TI  - Hemodynamic effects of creatine phosphate in patients with congestive heart
      failure: a double-blind comparison trial versus placebo.
AB  - BACKGROUND: The use of metabolic drugs effective in addition to conventional
      therapy represents a significant challenge in patients with left ventricular
      dysfunction. HYPOTHESIS: The aim of this double-blind, placebo-controlled study
      was to investigate the hemodynamic effects of acute intravenous (i.v.)
      administration of creatine phosphate (CP) and of short-term treatment in patients
      with congestive heart failure (CHF) from ischemic heart disease (IHD) or dilated
      cardiomyopathy in addition to conventional therapy. METHODS: We compared the
      hemodynamic effects of exogenous creatine phosphate (CP) and placebo in a double
      blind, crossover design study in 13 hospitalized patients (12 men, 1 woman, mean
      age 52 +/- 8 years) with CHF. All patients were in New York Heart Association
      (NYHA) class II-III and received conventional pharmacologic therapy for CHF; this
      was not changed during the study period. The study design consisted of two
      treatment periods (CP or placebo and placebo or CP, respectively) of 4 days each,
      separated by a 2-day washout interval. The intravenous infusion consisted of 6 g
      CP or placebo (acute treatment) or 6 g CP or placebo daily for 4 days (short-term
      treatment) diluted in 50 ml of NaCl 0.9%; infusion duration was about 10 min.
      Mono-bidimensional echocardiographic examination (Hewlett Packard Sonos 1000,
      with a 2.5 MHz transducer) was performed at baseline, after acute infusion, and
      12 h after the end of short-term treatment. Data were analyzed by ANOVA and
      Student's t-test for paired data; the results obtained after acute and short-term
      therapy were compared with the baseline values. RESULTS: After placebo therapy,
      no significant change was observed. The results after treatment with CP showed a
      significant reduction of end-systolic diameter [baseline: 4.5 +/- 0.6; acute: 4.2
      +/- 0.5, (p < 0.001); short-term 4.3 +/- 0.6 cm, (p < 0.05)] and systemic
      vascular resistance (baseline: 1064.9 +/- 483.7; acute: 947.5 +/- 390.2 (p <
      0.05); short-term: 950.7 +/- 394.3 dyne-s-cm-5 (p < 0.05); moreover, a
      significant increase of percent ejection fraction [baseline: 48 +/- 12%; acute 53
      +/- 12% (p < 0.01); short-term 52 +/- 11% (p < 0.01)], and of percent fractional
      shortening [baseline: 25 +/- 7; acute 28 +/- 8 (p < 0.05); short-term 28 +/- 7%
      (p < 0.05)] was observed. CONCLUSION: CP was shown to improve cardiac function,
      even in the presence of a conventional CHF pharmacologic therapy.

PMID- 8874989
TI  - Pathophysiologic significance of left ventricular hypertrophy in dilated
      cardiomyopathy.
AB  - BACKGROUND AND HYPOTHESIS: Patients with dilated cardiomyopathy (DCM) with left
      ventricular hypertrophy (LVH) have been found to have a better prognosis than
      patients without LVH. However, the pathophysiologic mechanism for that has not
      been investigated. We sought to clarify the pathophysiologic significance of LVH
      in DCM. METHODS: We performed isoproterenol infusion echocardiography (0.02
      micrograms/kg/min) in 17 patients with DCM, and measured plasma epinephrine and
      norepinephrine levels at rest and at the end of ergometer exercise in 14 of the
      17 patients. Patients were classified into groups according to the presence (9
      patients) (LVH+) or absence (8 patients) (LVH-) of LVH. Left ventricular
      hypertrophy was defined as an inter-ventricular thickness or posterior wall
      thickness > or = 13 mm. RESULTS: Although there was no significant difference
      between groups in fractional shortening at rest during isoproterenol infusion,
      fractional shortening was significantly higher in the LVH(+) group than in the
      LVH(-) group (29 +/- 9 vs. 17 +/- 8%; p < 0.025). Although there was no
      significant difference in plasma norepinephrine level, it was significantly lower
      in the LVH(+) group than in the LVH(-) group (233 +/- 169 vs. 519 +/- 258 pg/ml;
      p < 0.05) at the end point of the exercise. CONCLUSION: Systolic reserve,
      represented by the response to isoproterenol, is greater in patients with DCM
      with LVH than in those without LVH, and a lower plasma level of norepinephrine is
      needed to activate the myocardium during exercise in patients with DCM with LVH.
      This pathophysiologic characteristic could be one of the mechanisms which explain
      a better prognosis in patients with DCM with LVH.

PMID- 8874990
TI  - Evaluation of left ventricular relaxation using the continuous-wave Doppler
      velocity profile of aortic regurgitation: noninvasive measurement of left
      ventricular negative dP/dt and time constant.
AB  - BACKGROUND: The maximal negative dP/dt [max (-)dP/dt] and time constant (T) are
      useful indices for evaluating left ventricular (LV) relaxation, but they require
      invasive procedures. HYPOTHESIS: The purpose of this study was to obtain max (
      )dP/dt and T using the continuous-wave Doppler aortic regurgitation velocity
      curve (AR-CW) noninvasively. Using the Bernoulli equation, the AR-CW allows
      accurate determination of the pressure gradients (PG) between the aorta and the
      left ventricle. METHODS: In 10 patients with trivial to mild AR, the rising
      segment of the AR-CW reflecting LV pressure decrease was digitized with the
      cardiac image analysis system. Transpulmonary contrast-enhanced Doppler
      echocardiography was used in three patients to obtain intense velocity envelope.
      The PG curve and the firs derivative curve were reconstructed and the maximal
      point of the first derivative curve, which is consistent with max(-)dP/dt, was
      termed as maximal rate of pressure fall (maxRPF). As T (calculated according to
      the method of Weiss) can be obtained from T=Pm/max(-)dP/dt [Pm: LV pressure at
      the phase of max(-)dP/dt], we calculated T from Pm/maxRPF (Pm=dicrotic notch
      pressure-4Vm2) (Vm: AR velocity at the phase of maxRPF). RESULTS: The Doppler
      derived maxRPF and T (TD) approximated the catheter-derived max(-)dP/dt and T (y
      = 0.85x + 245, r = 0.97, p < 0.001, y = 0.79x + 4, r = 0.87, p < 0.001). In
      addition, dobutamine echocardiography was performed in nine patients showing
      increased maxRPF and decreased TD, indicating improvement of LV relaxation.
      CONCLUSION: These Doppler-derived new indices are sufficiently useful to evaluate
      LV relaxation noninvasively.

PMID- 8874991
TI  - Hemodynamic time course of acute and chronic isosorbide dinitrate treatment at
      rest and during exercise in patients with stable ischemic heart disease.
AB  - HYPOTHESIS: The study was undertaken to establish differences between venous and
      arterial isosorbide dinitrate (ISDN) effects during acute and chronic treatment,
      hemodynamics at rest, and during supine exercise. METHODS: These effects were
      assessed invasively in 16 patients with stable ischemic heart disease before and
      at hourly intervals for 4 h after administration of peroral 30 mg ISDN. Eight
      patients were previously untreated (acute group), and eight were treated with 30
      mg ISDN asymmetrically b.i.d. for two weeks (chronic group). RESULTS: Prior to
      ISDN administration, right atrial, mean pulmonary artery, pulmonary artery wedge,
      and mean arterial pressure (RAP, MPAP, PAWP, and MAP) rose from normal resting to
      pathologic values during exercise. One h after ISDN administration, all exercise
      pressures were normalized (p < 0.001). During the following 3 h, exercise RAP
      rose similarly in both groups (p < 0.01), while MPAP rose particularly in the
      chronic group (p < 0.001). Exercise PAWP and MAP, however, remained low in the
      acute group, but increased markedly in the chronic group (p < 0.01), particularly
      from the third to the fourth hour after ISDN. CONCLUSION: The daily, asymmetric
      administration of 30 mg ISDN b.i.d. maintained beneficial, anti-ischemic effects
      for 2 to 3 h after a morning dose of the drug, but thereafter attenuation of the
      effects occurred in the arteries but not in the veins.

PMID- 8874992
TI  - High prevalence of repolarization abnormalities in children with simple
      ventricular ectopy.
AB  - BACKGROUND: Premature ventricular contractions (PVCs) may occur in 0.3 to 2.2% of
      routine resting electrocardiograms (ECGs) in children with structurally normal
      hearts. HYPOTHESIS: This study tests the hypothesis that repolarization
      abnormalities are present more frequently on the surface ECG in pediatric
      patients with benign ventricular ectopy. METHODS: A retrospective study was
      performed examining 32 children with benign ventricular ectopy and structurally
      normal hearts. The surface ECG was carefully reviewed, concentrating on
      repolarization abnormalities as evidenced by a prolonged QTc, a prolonged JTc,
      and/or an abnormal T-wave vector. QTc was calculated using Bazett's formula and
      considered prolonged if > 440 ms, and the JTc was calculated using a formula
      analogous to Bazett's formula and considered prolonged if > 340 ms. The T-wave
      vector was considered normal if between 0 to +90 degrees, concordant with the
      frontal QRS axis and within 60 degrees of the QRS axis. There were 13 females
      (41%) and 19 males (59%) with an average age of 9.1 years (range 1-16.1 years).
      These patients were then compared with age- and gender-matched controls. Fourteen
      of 32 study patients (44%) and 2 of 32 controls (6%) had evidence of
      repolarization abnormalities. RESULTS: Using chi 2 analysis, there was a
      significant difference between groups (p = 0.0005). No patient had an abnormal T
      wave vector and there were no other significant ECG abnormalities. There was no
      significant relationship between repolarization abnormalities and patient gender
      or age. CONCLUSION: A significant percentage (44%; P = 0.0005) of children with
      benign ventricular ectopy have associated repolarization abnormalities as
      evidenced by a prolonged QTc and/or JTc. This finding suggests that children with
      "benign PVCs" may have repolarization changes indicative of underlying substrate
      abnormalities.

PMID- 8874993
TI  - On-line evaluation of systolic performance by densitometry in digital left
      ventriculography.
AB  - The angiocardiographic evaluation of left ventricular end-diastolic (LVEDV) and
      end-systolic (LVESV) volumes and ejection fraction (EF) is routinely performed by
      the area-length method (ALM) but may lead to erroneous results. Digital imaging
      in real time allows densitometric procedures of determining left ventricular (LV)
      performance to be applied alternatively. In this study, we present densitometric
      algorithms for the analysis of LVEDV, LVESV, and EF from digital image data,
      establish accuracy and reproducibility, and determine value and limitations in
      comparison with ALM in single-plane 30 degrees right anterior oblique (RAO)
      projection. A linear relationship between iodine depth and measured densities is
      mainly burdened with scatter radiation and beam hardening which reduce primary
      radiation and suppress iodine depth. However, facilities such as deconvolution
      and correction algorithms are capable of reducing these sources of error. In the
      present study, computer-analyzed contrast images of iodine-filled wedges and
      spheres showed a near-linear relationship between iodine depth between 50-100
      mg/cm2 and measured densities. Contrast images of heart casts and LV angio-grams
      of 54 patients were obtained with a digital image acquisition and processing
      system, and evaluated by two independent observers. The phantom study resulted in
      significantly (p < or = 0.01) better densitometric standard errors of estimate
      for volumes [3.3 ml densitometry (DENS) vs. 8.9 ml (ALM)] and simulated EF [4.3%
      (DENS) vs. 7.8% (ALM)] than ALM. The standard error of estimate for the
      comparison between both methods was 8.4 ml for volumes and 7.5% for EF.
      Densitometric volumes tended to underestimate volumes calculated by ALM. The
      angiographic study of patients demonstrated significant correlations between both
      methods (LVEDV r = 0.78, LVESV r = 0.83, total volumes: r = 0.89; EF r = 0.88).
      The standard errors of estimate can be ascribed to systematic, method-related
      errors of both DENS and ALM (LVEDV +/- 28.9 ml, LVESV +/- 23.4 ml, total volumes
      (EDV and ESV) +/- 27.1 ml; EF +/- 8.1%). The intra- and interobserver
      variability, respectively, exhibited significantly smaller (p < or = 0.01 and p <
      or = 0.05, respectively) standard errors of estimate for densitometric EF [4.6%
      (DENS) vs. 8.5% (ALM) and 7.1% (DENS) vs. 10.3% (ALM), respectively]. Inclined
      but not significant differences were found for LVEDV and LVESV. In conclusion,
      the data presented indicate that the calculation of LV volumes and EF in digital
      left ventriculography may be performed accurately by densitometric calculation in
      single-plane 30 degrees RAO projection. Minor underestimations in densitometric
      volume determination may be anticipated in the evaluation of LV geometry.

PMID- 8874994
TI  - Pacing therapy for atrial tachyarrhythmias.
AB  - The use of pacing techniques for the treatment of atrial tachyarrhythmias has
      been advocated for more than 30 years. Although it has played a beneficial role
      in the management of paroxysmal supraventricular tachycardia (PSVT) in drug
      refractory patients, tachycardia acceleration and development of atrial
      fibrillation has been the major drawback. With the availability of radiofrequency
      catheter ablation therapy, the use of implantable antitachycardia devices for
      PSVT is currently negligible. From retrospective and small control studies it has
      been shown that atrial or dual-chamber pacing in patients with sick sinus
      syndrome has been associated with a lower incidence of paroxysmal atrial flutter
      or fibrillation than in those who received a ventricular pacemaker. Furthermore,
      recent studies have reported the potential benefit of reducing frequency of
      paroxysmal atrial flutter and fibrillation with multisite atrial pacing. As a
      result, there is a resurgence of research interest in antitachycardia pacing for
      prevention of atrial tachyarrhythmias. This paper briefly describes the basic
      aspects of antitachycardia pacing, reviews the data on the use of implantable
      antitachycardia devices for PSVT and the selection of patients, and assesses the
      current status of research on atrial pacing for prevention of paroxysmal atrial
      flutter and fibrillation.

PMID- 8874995
TI  - Coronary artery and saphenous vein graft remodeling: a review of histologic
      findings after various interventional procedures--Part I.
AB  - Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of
      acutely and chronically obstructed coronary artery vessels. It is also the
      centerpiece for various new intervention techniques. Their morphologic effects on
      the site of obstruction has been termed "remodeling." Part I of this six-part
      series focuses on mechanisms of remodeling after various interventional
      techniques, particularly balloon angioplasty.

PMID- 8874996
TI  - Echocardiographic assessment of wall motion in ST-segment alternans during
      coronary angioplasty.
AB  - ST alternans occurs in the setting of severe and extensive myocardial ischemia.
      In this particular case, ST alternans occurred well after the onset of ischemia
      induced left ventricular dysfunction. There is no echocardiographic evidence of
      beat-to-beat variation in contractility to correspond to this ST-segment
      phenomenon. Further studies of left ventricular function during ST alternans in
      patients are needed to determine whether this finding applies to all patients
      with ischemic heart disease.

PMID- 8874997
TI  - Radiofrequency catheter ablation of a right atriofascicular (Mahaim) and two
      atrioventricular (Kent) accessory pathways in a single session.
AB  - This report describes the case of a 19-year-old patient with Ebstein's anomaly,
      who had an unusual combination of a right atriofascicular (Mahaim) and two
      ipsilateral right atrioventricular (Kent) accessory pathways participating in
      three types of antidromic and orthodromic reciprocating tachycardias in the
      absence of retrograde conduction over the bundle of His-atrioventricular node
      axis. All three pathways were ablated in a single session using temperature
      guided radiofrequency current.

PMID- 8874998
TI  - Provocation of coronary spasm by dobutamine stress echocardiography in a patient
      with angiographically minimal coronary artery disease.
AB  - Dobutamine stress echocardiography (DSE) has been widely used for the noninvasive
      diagnosis of obstructive coronary artery disease. The ST-segment elevation during
      DSE has been reported as an infrequent event, caused by old myocardial infarction
      and/or critical coronary narrowings. The patient presented here was a 35-year-old
      man with a recent history of nonexertional chest pain. He had
      hypercholesterolemia and a history of heavy smoking as risk factors. The patient
      developed ST-segment elevation with chest pain during 40 mcg/min dobutamine
      infusion for the stress echocardiographic examination. Subsequent coronary
      angiograms revealed only mild coronary atherosclerosis. It is speculated that
      coronary spasm occurred in this patient as a paradoxical response to increased
      coronary blood flow with dobutamine administration.

PMID- 8874999
TI  - Elevated serum Lp(a) concentration and the rare apo(a) phenotype in a patient
      with myocardial infarction.
AB  - Lp(a) is considered to be an independent risk factor for the development of
      cardiovascular disease. A case of myocardial infarction with elevated serum Lp(a)
      concentration and the rare apo(a) phenotype and its successful recanalization
      using tissue plasminogen activator is reported.

PMID- 8875000
TI  - Marie-Francois-Xavier Bichat.

PMID- 8875001
TI  - Intubation of critically ill patients.
AB  - Airway management of critically ill patients has been enhanced by the recent
      introduction of several new types of artificial airways and laryngoscopes. New
      drugs for sedation and neuromuscular blockade have been developed to facilitate
      care of the intubated patient. Guidelines for management of the difficult airway
      have been introduced. Several new prospective studies have improved our
      understanding of complications of intubation and how to avoid these sometimes
      tragic events. A consensus is evolving that TLI and tracheotomy each have clear
      advantages and disadvantages in prolonged airway maintenance and that multiple
      factors, not simply the duration of TLI, must be considered in the optimal timing
      of tracheotomy for each patient. Complex medicolegal and ethical issues directly
      impact intubation, perhaps more so than any other practice in critical care
      medicine. Physicians who care for critically ill patients should be familiar with
      these recent developments and concepts in airway management.

PMID- 8875002
TI  - Auto-positive end-expiratory pressure and dynamic hyperinflation.
AB  - PEEP is indicated in patients with COPD only to unload the respiratory muscles
      from the auto-PEEP resulting from expiratory flow limitation. If auto-PEEP is not
      caused by flow limitation, application of PEEP will cause further hyperinflation,
      worsening respiratory mechanics, muscle activity, and hemodynamics. To assess the
      presence of expiratory flow limitation correctly, to measure auto-PEEP correctly,
      and to identify the maximal PEEP level to be used, measurements of flow and
      opening pressure must be obtained during a brief period of suspended respiratory
      muscle activity (obtained by sedation) with the patient's own breathing pattern
      reproduced accurately.

PMID- 8875003
TI  - Pressure-controlled and volume-cycled mechanical ventilation.
AB  - Pressure and volume modes of mechanical ventilation are available as options in
      the current generation of ventilators, giving clinicians many choices when
      managing a mechanically ventilated patient. In volume cycled ventilation, tidal
      volume is set and airway pressures are measured, whereas in pressure-controlled
      ventilation, pressure is set and volume is measured. This article reviews the
      characteristics of these two ventilatory modes and discusses in detail conversion
      from one mode to the other. Pertinent clinical studies and recent direct
      comparisons of volume-cycled and pressure-controlled ventilation are reviewed.

PMID- 8875004
TI  - New modes of mechanical ventilation.
AB  - Many new approaches to mechanical ventilation have been developed. This article
      discusses these new strategies and modes. These include lung protection
      conventional ventilation strategies, long inspiratory time strategies, pressure
      targeted breath enhancements, airway pressure-related release ventilation, and
      proportional-assist ventilation.

PMID- 8875005
TI  - Patient-ventilator interactions.
AB  - Patient-ventilator synchrony is important in the management of the ventilator
      dependent patient. Factors inherent to the patient and the ventilator influence
      patient-ventilator synchrony. Detection of patient-ventilator synchrony may
      require monitoring of airway pressure and flow waveforms.

PMID- 8875006
TI  - Complications of mechanical ventilation. A bedside approach.
AB  - Instead of cataloging complications reported to occur during mechanical
      ventilation, the authors have discussed the potential causes for several common
      scenarios in the management of ventilated patients. These include the new
      development of hypotension, acute respiratory distress (fighting the ventilator),
      repeated sounding of the ventilator's high-pressure alarm, hypoxemia, blood from
      the endotracheal tube, and the problem of diagnosing VAP. In the course of
      considering likely explanations for this group of circumstances for which the
      clinician is consulted or called to the bedside, virtually all reported
      ventilator-associated complications must be discussed. This new approach to an
      important aspect of ICU care may aid in clinical problem-solving and reduce the
      likelihood that a diagnosis will be missed or inappropriate measures taken in the
      absence of a systematic, pathophysiology-based approach.

PMID- 8875007
TI  - Monitoring during mechanical ventilation.
AB  - Approximately half of the patients admitted to an ICU are admitted for the
      purposes of monitoring rather than interventional therapy. In the last decade,
      significant technologic advances have enhanced monitoring capacities, and the
      understanding of the pathophysiology of respiratory failure has improved pari
      passu, allowing clinicians to employ monitors in a more intelligent manner. This
      article deals with new developments in arterial blood gas monitoring, pulse
      oximetry, capnometry, and monitoring of neuromuscular function and pulmonary
      mechanics, emphasizing issues most relevant to mechanical ventilation.

PMID- 8875008
TI  - Weaning from ventilatory support.
AB  - Resumption of spontaneous unassisted breathing after an episode of acute
      respiratory failure often is achieved without major difficulty. In a significant
      number of patients however, weaning from mechanical ventilation is a long and
      difficult process that markedly increases the duration of mechanical ventilation
      and consumes a significant fraction of critical care resources. Some criteria
      have been suggested to predict early and more accurately the moment the patient
      is ready to be separated from the ventilator. At the present time, the f/VT ratio
      (rapid shallow breathing index) appears to yield the best predictive power. None
      of these indices, however, is powerful enough to be relied on solely, and their
      use should be limited to that of aids to the critical care physician. The
      inability to sustain spontaneous ventilation usually is the consequence of an
      imbalance between respiratory demand and respiratory muscle capacity. Increased
      elastic workload, increased resistive workload, and increased VE are the main
      causes of excessive demand imposed on the respiratory system. Respiratory muscle
      pump failure usually relates to peripheral nerve dysfunction or muscular
      dysfunction. Left ventricular dysfunction also is an important cause of weaning
      failure. The usual methods of weaning from mechanical ventilation are T-piece
      trials with abrupt definitive discontinuation of mechanical ventilation if
      tolerated or with progressive intermittent trials, IMV, and PSV. All have their
      advantages and disadvantages, and the method of weaning per se is not the only
      critical factor. Although their conclusions were different regarding the best
      method of weaning, however, two recent clinical trials suggest that ventilatory
      management has a major influence on the outcome of weaning from mechanical
      ventilation in difficult-to-wean patients. The global management of such patients
      requires a systematic approach with consideration of all factors involved in the
      process of separation from the ventilator. New computer-assisted systems already
      are tested and, in the future, may provide a significant advantage in the
      management of weaning from mechanical ventilation.

PMID- 8875009
TI  - Adjuncts to mechanical ventilation.
AB  - Adjunctive ventilatory strategies have been developed to improve oxygenation and
      carbon dioxide (CO2) removal during mechanical ventilation of critically ill
      patients. These techniques allow clinicians to attain their clinical goals at
      lower levels of ventilatory support. In this article, the authors discuss
      extracorporeal CO2 removal, venovenous intravena caval oxygenator, and tracheal
      gas insufflation as adjuncts to CO2 removal and nitric oxide, surfactant
      replacement therapy, perfluorocarbon-associated gas exchange, and prone
      positioning as adjuncts to oxygenation.

PMID- 8875010
TI  - Noninvasive positive-pressure ventilation in patients with acute respiratory
      failure.
AB  - This article provides a systematic review of the literature on the application of
      noninvasive ventilation in various forms of hypercapnic and hypoxemic respiratory
      failures. A description of the underlying pathophysiology is followed by a review
      of physiologic data explaining the mechanisms of action of noninvasive
      ventilation. A critical review of clinical studies is presented with specific
      suggestions. The methodology of correctly implementing and monitoring noninvasive
      ventilation in patients with acute respiratory failure, critical to success, is
      detailed.

PMID- 8875011
TI  - Evolving concepts in the ventilatory management of acute respiratory distress
      syndrome.
AB  - With few modifications, a high tidal volume, normoxic, normocapnic ventilation
      paradigm developed as the standard approach to supporting most critically ill
      patients. Large tidal volumes, high end-tidal (plateau) alveolar pressures, and
      low levels of positive end-expiratory pressure are still common in many ICUs
      during ventilation of acute respiratory distress syndrome (ARDS). A body of
      scientific literature now suggests that this traditional approach may retard
      healing of the injured lung. A relatively small but growing number of
      practitioners are shifting their first priority from optimizing oxygen exchange,
      oxygen delivery, or respiratory system compliance to ensuring adequate lung
      protection. This article reviews the basis for concern about traditional
      ventilatory support in ARDS and develops an approach based on current evidence
      and newer options for management.

PMID- 8875012
TI  - Mechanical ventilation in obstructive lung disease.
AB  - This article reviews selected topics relevant to the use of mechanical
      ventilation in patients with severe airflow obstruction. Areas discussed include
      the bedside assessment of respiratory system mechanics, the ventilatory
      determinants of dynamic pulmonary hyperinflation, the role of controlled
      hypoventilation with permissive hypercapnia, and the delivery of bronchodilators
      during mechanical ventilation.

PMID- 8875013
TI  - Independent lung ventilation.
AB  - Situations in which independent lung ventilation may be of use include massive
      hemoptysis, pulmonary alveolar proteinosis, risk of interbronchial aspiration,
      unilateral lung injury, single lung transplant, and BPF. Any decision to attempt
      independent lung ventilation should take into consideration the many technical
      difficulties associated with the procedure. They include difficulties in the
      placement of DLTs and monitoring tube position, the risk of tube displacement,
      and the risk of airway trauma. The clinician also must consider the costs in
      terms of available manpower and resources. Maintaining a patient on independent
      lung ventilation requires highly skilled nursing care, specialized monitoring
      devices, and readily available FOB. Even with these limitations, independent lung
      ventilation may be of use in certain clinical situations when standard methods
      have failed.

PMID- 8875014
TI  - Mechanical ventilation of the newborn. An overview.
AB  - Mechanical ventilation of the newborn infant is an ever-changing area. Its
      evolution has been hampered and stimulated by problems of small size, inadequate
      technology, unexpected complications, and changing expectations. With
      synchronized ventilation, a new technique in the neonatal ICU, clinicians again
      are reassessing their assumptions. HFV, a "new" technique for 15 years, has found
      a niche in the treatment of infants failing CV. Its use as an initial therapy for
      RDS, advocated by some, remains controversial. Monitoring gas flow patterns,
      tidal and minute volumes, and lung mechanics has become a part of the CV, but
      complications still occur. The only thing certain is that change will continue.

PMID- 8875015
TI  - The OpenLabs Project.

PMID- 8875016
TI  - User requirements on the future laboratory information systems.
AB  - Today numerous information technology solutions exist for the clinical laboratory
      which operate either as stand-alone functionalities or with ad hoc integration
      solutions. The OpenLabs (A2028) AIM Project puts emphasis on the design and
      specification of a framework for the interoperability of existing systems and new
      advanced services, and consequently concentrates on the issue of integration. The
      purpose of the OpenLabs open architecture is to serve as a functional solution to
      this integration. A basic principle for this open architecture is that each of
      the advanced services shall be able to function individually or in any
      combination with an existing Laboratory Information System (LIS), and that it
      shall enable new modular functionalities to be incorporated in a 'plug-and-play'
      fashion. The synthesis of the main user needs and requirements implies that the
      future IT solutions: (a) must be highly flexible and maximally customizable--by
      the users themselves; (b) are based on the concept of open systems, both
      technically and functionally, which enables modular functionalities from
      different vendors to co-operate forming a global LIS functionality; (c) are
      future viable and able to incorporate already installed IT functionalities; (d)
      support management of failure prevention, of repair, of success, and of change.
      The establishment of an open architecture implies that a market will develop for
      modular, scaleable, and cost-effective LIS features without today's dependence on
      individual manufacturers and hardware/software platforms.

PMID- 8875017
TI  - Specifying an open clinical laboratory information system.
AB  - This paper presents an overview of the architectural infrastructure in which
      existing laboratory information systems can be made to interoperate with
      additional modules offering a range of advanced clinical laboratory
      functionalities. The infrastructure is based on an open distributed computing
      platform, and its specification is described using the open distributed
      processing reference model.

PMID- 8875018
TI  - Computational viewpoint of the OpenLabs architecture.
AB  - The computational viewpoint of the OpenLabs architecture specification
      concentrates on the definition of the functional interfaces between the logical
      modules that make up the clinical laboratory as defined in the enterprise and
      information viewpoints. A method is presented which transforms the information
      models into a specification written in Abstract Syntax Notation One (ASN.1). It
      is then shown how the specification can be translated into an Interface
      Definition Language (IDL) of a 'middleware' product which can then be compiled
      for implementation on a distributed system.

PMID- 8875019
TI  - Managing the operation of open distributed laboratory information systems.
AB  - This paper examines how the concepts and designs of workflow management systems
      and distributed systems management can be integrated and customized to manage
      open laboratory computing services. The paper outlines the objectives of managing
      laboratory computing services and identifies techniques and designs which
      facilitate this management. The paper also outlines the implementation of an open
      laboratory service management system.

PMID- 8875020
TI  - OpenLabs services for ordering laboratory investigations.
AB  - An automated system is described that screens requests for laboratory
      investigations from GPs and delivers feedback with respect to the adequacy of the
      requests. The system has to replace and extend the current system in which
      feedback is provided on a manual basis each half year, based on the tests
      requested during a period of one month, randomly selected from the previous half
      year. It has been reported elsewhere that the manual system reduced the number of
      tests requested considerably. The criteria used by the automated system and the
      manual system are based on guidelines and work agreements that GPs have agreed to
      follow when requesting investigations. It is concluded that the automated system
      is very user-friendly and that in the order of 4-17% of the requested tests could
      be identified as unnecessary, with a false negative rate in between 4% (for
      hyperthyroidism) and 23% (for hypothyroidism). The achieved reduction in the
      number of tests is in addition to the reduction obtained in the manual system.

PMID- 8875021
TI  - OpenLabs advanced instrument workstation services.
AB  - The advanced instrument workstation (AIW) is one of a number of system modules
      developed in the OpenLabs project, offering advanced services that complement the
      basic services available from laboratory information systems (LIS) in general.
      The AIW services relate to instrument interfacing, user interfacing, quality
      control, calibration verification, patient result validation, local and remote
      fault diagnosis and maintenance, and external quality assessment (EQA) by
      external organisations.

PMID- 8875022
TI  - Patient result validation services.
AB  - Patient result validation is a vital final stage of laboratory quality assurance
      and is usually the responsibility of senior laboratory staff. Computerised
      validation systems have recently been introduced to autovalidate data meeting
      certain pre-defined criteria, thereby allowing senior staff to focus on
      problematic cases. This article describes the patient results validation service
      module developed for an advanced instrument workstation in the OpenLabs project.
      Using knowledge-based techniques, the module provides a range of locally
      configurable advanced validation procedures (e.g., internal consistency checks,
      delta checks, and checks for selected specific errors) in addition to the
      standard reference range and pathological limits checks offered by many
      laboratory information systems.

PMID- 8875023
TI  - The research in semantics behind the OpenLabs coding system.
AB  - The OpenLabs coding system is an established, comprehensive, dynamic, flexible,
      open, multilingual European system which is tailored to meet the electronic data
      interchange (EDI) needs of medical laboratory users. The OpenLabs coding system,
      having many specific, independent classes and considerable flexibility, serves
      two different objectives: (i) unambiguous coding of entities present in messages
      used for EDI in clinical pathology; and (ii) interfacing with other nomenclatures
      and coding schemes to map concepts between different systems.

PMID- 8875024
TI  - Remote instrument telemaintenance.
AB  - In the past decade, great technological progress has been made in telemaintenance
      of mainframe and mini computers. As hardware technology is now available at an
      acceptable cost, computer aided trouble-shooting can be adapted to laboratory
      instrumentation in order to significantly improve repair time, avoid instrument
      downtime by taking advantage of predictive methods, and provide general
      diagnostic assistance. Depending on the size of the instrument, the
      telemaintenance facility can be dedicated to a single instrument or alternatively
      a telemaintenance server can manage multiple distributed small instruments
      through a Local Area Network. As complex failures can occur, the local diagnosis
      capabilities may be exceeded and automatic dialing for connection to computerized
      Remote Maintenance Centers is needed. The main advantages of such a centre, as
      compared to local diagnosis systems, are the increased access to more information
      and experience of failures from instrument installations, and consequently the
      provision of training data updates for Artificial Neural Networks and Knowledge
      Based Systems in general. When an abnormal situation is detected or anticipated
      by a diagnosis module, an automatic alert is given to the user, local diagnosis
      is activated, and for simple solutions, instructions are given to the operator.
      In the last resort, a human expert can be alerted who, with remote control tools,
      can attend to the failures. For both local and remote trouble-shooting, the data
      provided by the instrument and connected workstation is of paramount importance
      for the efficiency and accuracy of the diagnosis. Equally, the importance of
      standardization of telemaintenance communication protocols is addressed.

PMID- 8875025
TI  - Advanced management facilities for clinical laboratories.
AB  - As part of the OpenLabs (AIM 2028) programme a decision support system (DSS) for
      laboratory capacity management has been developed. This DSS contains a simulation
      module for determining the performance of planning rules given the equipment and
      staffing of the clinical laboratory and the demand for laboratory services. User
      requirements are discussed and a method is developed to (re-)define rules
      concerning various planning decisions. To show the functionality of the
      simulation module some simulation experiments are described.

PMID- 8875026
TI  - Cobalamin.
AB  - Cobalamin (vitamin B12) is an essential nutrient derived exclusively from
      bacterial sources. It is an essential cofactor for three known enzymatic
      reactions. Untreated deficiency, caused by either the autoimmune disease
      pernicious anemia or nutritional lack, results in a macrocytic anemia and/or
      subacute combined degeneration of the spinal cord and is eventually fatal.
      Cobalamin in serum is bound to two proteins, transcobalamin and haptocorrin. The
      former is responsible for the essential delivery of cobalamin to most tissues.
      Inadequate tissue availability of cobalamin results in increased concentration of
      methylmalonic acid and homocyst(e)ine due to inhibition of methylmalonyl-CoA
      mutase and methionine synthase, respectively. Strict vegetarians have long been
      known to be at risk of cobalamin deficiency, which develops insidiously over many
      years. It is now clear that a significant number of the elderly and HIV-positive
      individuals are also at increased risk of deficiency. Any individual with reduced
      ability to split cobalamin from food-protein may also become deficient even
      though intrinsic factor is present. Diagnosis of cobalamin deficiency has
      frequently relied on total serum cobalamin and the Schilling test. Newer
      approaches such as analysis of methylmalonic acid, homocyst(e)ine,
      holotranscobalamin, anti-intrinsic factor antibodies, and serum gastrin may
      provide more cost-effective testing, as well as identify those with a covert
      deficiency.

PMID- 8875027
TI  - Dynamics of the pulpo-dentin complex.
AB  - Dentin has a relatively high water content due to its tubular structure. Once
      dentin is exposed, this intratubular water is free to move in response to
      thermal, osmotic, evaporative, or tactile stimuli. Fluid shifts across dentin are
      thought to cause sufficient shear forces on odontoblasts, nerve endings, nearby
      fibroblasts, and blood vessels to cause significant mechanical irritation,
      disruption, or damage, depending on the magnitude of the fluid shift. Even in the
      absence of fluid shifts, the water-filled tubules provide diffusion channels for
      noxious (i.e., bacterial products) substances which diffuse inward toward the
      pulp, where they can activate the immune system, provide chemotactic stimuli,
      cytokine production, and produce pain and pulpal inflammation. Viewed from this
      perspective, dentin is a poor barrier to external irritants. However, pulpal
      tissues react to these challenges by increasing the activity of nerves, blood
      vessels, the immune system, and interstitial fluid turnover, to make the exposed
      dentin less permeable either physiologically, via increased outward fluid flow,
      or microscopically, by lining tubules with proteins, mineral deposits, or
      tertiary dentin, thereby enhancing the barrier properties of dentin, and
      providing additional protection to pulpal tissues. These reactions involve dentin
      and pulp, both in the initiation of the processes and in their resolution. These
      responses of the dental pulp to irritation of dentin demonstrate the dynamic
      nature of the pulpo-dentin complex.

PMID- 8875028
TI  - Recent advances in ceramics for dentistry.
AB  - For the last ten years, the application of high-technology processes to dental
      ceramics allowed for the development of new materials such as heat-pressed,
      injection-molded, and slip-cast ceramics and glass-ceramics. The purpose of the
      present paper is to review advances in new materials and processes available for
      making all-ceramic dental restorations. Concepts on the structure and
      strengthening mechanisms of dental ceramics are provided. Major developments in
      materials for all-ceramic restorations are addressed. These advances include
      improved processing techniques and greater mechanical properties. An overview of
      the processing techniques available for all-ceramic materials is given, including
      sintering, casting, machining, slip-casting, and heat-pressing. The most recent
      ceramic materials are reviewed with respect to their principal crystalline
      phases, including leucite, alumina, forsterite, zirconia, mica, hydroxyapatite,
      lithium disilicate, sanidine, and spinel. Finally, a summary of flexural strength
      data available for all-ceramic materials is included.

PMID- 8875029
TI  - Current concepts of autoimmune exocrinopathy: immunologic mechanisms in the
      salivary pathology of Sjogren's syndrome.
AB  - Sjogren's syndrome is a systemic autoimmune disorder characterized by symptoms of
      oral and ocular dryness and a chronic, progressive loss of salivary and lacrimal
      function. The exocrine involvement is the result of a focal, peri-ductal
      mononuclear cell infiltrate and the subsequent loss of secretory epithelial
      cells. The mechanisms of this autoimmune exocrinopathy are not understood fully.
      Many recent investigations have described alterations in a number of immune
      mediators within the salivary glands. These studies provide new insights into the
      immune regulation of normal salivary gland functions and the mechanisms of gland
      damage in Sjogren's syndrome.

PMID- 8875030
TI  - Neural control of pulpal blood flow.
AB  - Blood flow of mammalian dental pulp is under both remote and local control. There
      is evidence for the existence of parasympathetic nerves in the pulp, but
      functionally the cholinergic influence is weak, and the physiological
      significance of this autonomic system seems to be low. The evidence for
      sympathetic vasoconstrictor nerves in the pulp is robust, and there is convincing
      support for the contention that these nerves play a physiological role, operating
      via release of noradrenaline and neuropeptide Y. However, there is no significant
      functional evidence in support of sympathetic beta-adrenoceptor-mediated
      vasodilation in the pulp. The local control of blood flow involves a subset of
      intradental sensory nerves. By virtue of their neuropeptide content, these
      afferent fibers cause vasodilation and inhibit sympathetic vasoconstriction in
      response to painful stimulation of the tooth. Such locally governed control may
      serve to meet immediate demands of the pulp tissue. A locally triggered reflex
      activation of sympathetic nerves in the pulp may modulate this control and limit
      its magnitude. Thus, there are competitive interactions between local and remote
      vascular controls which may be put out of balance in the injured and inflamed
      dental pulp.

PMID- 8875031
TI  - Bioavailability of components of resin-based materials which are applied to
      teeth.
AB  - Chemical components of many materials used in dental practice can move into the
      local biophase, where they can have beneficial or adverse effects. The strongest
      indirect evidence that components of resin-based materials used in dentistry can
      move into the biophase are the many reports of allergic dermatitis in dental
      personnel. Direct measurement of component release has shown that triethylene
      glycol dimethacrylate (TEGDMA), hydroxyethyl methacrylate (HEMA), and, in the
      case of some orthodontic cements, bis-glycidyl methacrylate and benzoyl peroxide
      can move into an aqueous medium from a range of resin-based materials which are
      applied to teeth as part of oral care. In the case of resin composite
      restorations, HEMA and TEGDMA are available in microgram quantities via the
      salivary surface in the minutes and hours after clinical placement and via dentin
      and pulp in the hours and days after placement. Fortunately, moderate thickness
      of dentin protects pulp tissue against local toxicity. There are no data which
      suggest that systemic toxicity is a risk with any of these materials. There are
      some case reports of allergic responses to the monomers in patients, but the
      incidence of such responses appears at present to be much lower than that in
      dental personnel.

PMID- 8875032
TI  - Human oral microbial ecology and dental caries and periodontal diseases.
AB  - In the human oral cavity, which is an open growth system, bacteria must first
      adhere to a surface in order to be able to colonize. Ability to colonize a non
      shedding tooth surface is necessary prior to any odontopathic or periodontopathic
      process. Complex microbe-host relationships occur and must be studied before the
      commensal-to-pathogenic nature of the human indigenous oral flora can be
      understood. Medical pathogens, if present in the appropriate host, always produce
      specific disease. Caries and periodontal diseases are conditional diseases,
      requiring numbers of certain indigenous species at various sites, particularly
      the tooth surface. In the case of caries, the condition is related to sugar
      consumption. Periodontal disease/s may require certain host and environmental
      conditions, such as local environment or nutritional factors in gingival
      crevicular fluids. Nonetheless, critical numbers of certain indigenous species
      must be present in order for these diseases to occur. The aim of this review is
      to understand the acquisition of the indigenous oral flora and the development of
      human dental plaque. The role of the salivary pellicle and adherence of
      indigenous bacteria to it are critical first steps in plaque development.
      Bacterial interactions with saliva, nutritional factors, growth factors, and
      microbial physiologic processes are all involved in the overall process of
      microbial colonization.

PMID- 8875033
TI  - Endoscopic surgery: yes, but ...

PMID- 8875034
TI  - Hysteroscopy or ultrasound?
AB  - The methods of evaluation of the uterus and in particular of the endometrium are
      the subject of a heated debate, but only because those who argue are trying to
      establish one single technique which is all-encompassing and 100% accurate. Such
      specifications are very hard to identify in any technique and consequently we
      have to have an open mind as to what the patient needs and what combination of
      methods are to be used to achieve the diagnostic goal.

PMID- 8875035
TI  - Myomectomies by endo-uterine resection.
AB  - Endo-uterine resection is a true surgical act, well defined and atraumatic. To
      perform elective and complete one-stage hysteroscopic myomectomies, sparing
      normal myometrium, is not easy. Endometrial ablations provoking synaechie and
      adenomyosis should not be added to myomectomies. Complications of hysteroscopic
      surgery may be threatening and must be prevented.

PMID- 8875036
TI  - The role of salpingoscopy and falloposcopy in infertility.

PMID- 8875037
TI  - Laparoscopic surgery for ovarian cysts.
AB  - Laparoscopic surgery for ovarian cysts is one of the most frequent laparoscopic
      surgical procedures performed presently. The routine use of pelvic imaging
      (sonography), in the case of any gynaecological symptom or as a screening method
      in women at risk, explains why more and more ovarian cysts are encountered. The
      diagnostic and therapeutic challenge for the clinician to provide the best
      immediate and long-term benefits for the patient is to identify pre-operatively
      not only an ovarian malignancy (to be treated in a conventional way) but also
      functional cysts (usually disappearing spontaneously and requiring no form of
      treatment in most cases). Ideally, only benign 'organic' cysts should be treated
      laparoscopically. The technical aspects and the benefits of this approach have
      been documented extensively in recent years. The routine use of the 'closed
      technique' and of an impermeable bag for removal should limit the risk of
      spillage of the cyst contents with its inherent potential problems (chemical
      peritonitis, malignant cell dissemination and parietal implantation into the
      laparoscopic port sites). The adnexal torsion can be also properly managed by
      laparoscopic surgery.

PMID- 8875038
TI  - Surgical anatomy and dissection techniques for laparoscopic surgery.
AB  - All anatomically important pelvic structures lie embedded in the fatty-fibrous
      connective tissue of the retroperitoneum from which they may be freed by blunt
      dissection in the correct tissue planes. By relying on fixed laparoscopic
      landmarks, the correct surgical planes of dissection can be found, and all vital
      structures freed and identified by a systematic dissection consisting of a
      precise sequence of operative steps. Once the retroperitoneal dissection has been
      completed and all vital structures identified, most gynecologic operations can be
      carried out safely and without much difficulty laparoscopically. A nonanatomical
      approach to laparoscopic pelvic surgery may be easier to learn, but it is neither
      very versatile nor very safe except in the simplest of cases.

PMID- 8875039
TI  - Training and accreditation in endoscopic surgery.
AB  - Increasing concerns following the rapid uptake of endoscopic procedures into
      routine use and a small number of serious adverse patient outcomes have
      precipitated calls for guidelines on training and accreditation. A number of
      international colleges and societies have produced recommendations, although a
      number of inherent problems remain in the implementation of these. The published
      literature in the field is quite limited at present, but will undoubtedly expand
      rapidly.

PMID- 8875041
TI  - Outcomes-oriented research and managed care.

PMID- 8875040
TI  - Randomized studies in endoscopic surgery--where is the proof?
AB  - We have attempted to review the best available evidence for the commonest
      gynaecological endoscopic procedures. Controlled studies are the exception rather
      than the rule, and randomized studies are even rarer. Therefore, the results of
      large, uncontrolled series must be acknowledged. As a result, for most
      procedures, sufficient information is now available regarding indications,
      efficacy, and complications to determine their role in routine clinical practice.

PMID- 8875042
TI  - Audit in obstetrics.
AB  - Audit is developing both in theory and practice. This article highlights topics
      suitable for clinical audit across the whole range of pregnancy care. Many of the
      examples chosen specifically relate to recent publications that have attempted to
      set clear guidelines and standards, which can thus be audited. The topics have
      also been chosen to illustrate the different perspectives of audit, enabling
      hospitals to develop a varied, interesting and relevant audit programme.

PMID- 8875043
TI  - Infertility services in a managed care environment.
AB  - Managed care schemes are replacing traditional fee-for-service reimbursement to
      physicians and hospitals in the United States. Managed care schemes take the form
      of discounted fee-for-service, utilization review, global fee reimbursement, and
      capitated reimbursement schemes with funds to be distributed among providers.
      Reimbursement for infertility services has been excluded from many managed care
      plans as infertility is viewed as a social condition, not a medical condition,
      and coverage for infertility diagnosis and treatment is viewed as unnecessary in
      the bundle of services offered by insurers and other managed care organizations.
      However, some states mandate infertility coverage and some managed care
      organizations realize that provision of care for infertile couples makes their
      product more attractive. Large managed care organizations such as Blue Cross/Blue
      Shield of illinois and some entrepreneurial organizations are developing managed
      care plans that incorporate infertility services. Comprehensive services-
      including in-vitro fertilization--can be offered at a lower cost than traditional
      fee-for-service care. Newer technologies such as in-vitro fertilization are
      replacing fallopian tube surgery and surgical treatment for male infertility.
      These can be implemented at a lower cost and with better outcome for infertile
      couples than traditional services.

PMID- 8875044
TI  - Managed care of infertility.
AB  - Mandated managed care of infertility, as for other branches of medicine, demands
      cost-effectiveness, appropriate use of proven clinical methods, and audit of the
      services provided. Proper standards, and protocols of clinical diagnosis and
      selection of treatment need to be agreed, although allowing for valid
      alternatives. A diagnostic process and classification staged for primary,
      secondary, and tertiary care as appropriate, which has been derived by consensus,
      is offered in this paper. It is assumed that all couples would be allowed access
      to diagnostic services. A national estimate has attributed one-quarter of the
      costs of full infertility services to diagnostic procedures and three-quarters to
      treatments. It is assumed that any constraints owing to funding would apply only
      to access to treatment. One model proposed would limit treatment to those couples
      and methods which could achieve a 50% birthrate target within a reasonable time
      limit or number of cycles. Although there is as yet no existing model of managed
      care on which to base exact costing, it should be possible by initial over
      restrictiveness to leave room for annual adjustments of treatment provision and
      to allow for new developments. Other more equitable ways of sharing resources can
      be argued, and ethical standards should be agreed in any system of managed care
      for a population.

PMID- 8875046
TI  - Managed care in reconstructive pelvic surgery and urogynecology.
AB  - While demographic changes in future decades should expand the need for
      subspecialists in reconstructive pelvic surgery and urogynecology, managed care
      will probably limit access of patients to specialists in this field. Much of the
      evaluation and treatment for women with prolapse and incontinence will be
      provided by primary care providers.

PMID- 8875045
TI  - Managed care in benign gynecology.
AB  - Although managed care has been viewed by many as an intrusion into medical
      practice, the stated goals of its proponents are to improve practice outcomes in
      a cost-effective manner and change the focus of health care to disease prevention
      and rational clinical resource utilization. Because health care costs have risen
      consistently in excess of normal inflation, pressure has mounted to move away
      from traditional fee-for-service reimbursement and indemnity insurance to
      capitated payment and 'third party' managed care. Studies have shown that the
      number of providers of gynecologic care is currently in excess of demand based on
      a managed-care model. Success in managed care will therefore require an
      understanding of the new economics of health care and a commitment to the
      appropriate use of medical and surgical interventions. Research should focus on
      identifying and reducing the unintended and wasteful variation in practice style
      that currently exists for benign gynecology and all of health care. Clinical
      guidelines that are derived from actual measured outcomes and adjusted for
      severity of illness and co-morbid conditions should replace 'clinical opinion'
      and allow gynecologists to efficiently manage patients with a minimum of third
      party interference.

PMID- 8875047
TI  - Managed care in gynecologic oncology.
AB  - We review the recent literature on managed care and its application to
      gynecologic oncology. Although the literature is limited, we discuss professional
      agreement contracts, the role of primary care physicians and specialists in
      gynecologic cancer screening, changes in health care distribution, changes in
      physician-patient relationships, and cancer research.

PMID- 8875048
TI  - Managed care in obstetrics.
AB  - Managed care has evolved from an experiment in cost-containment to a major force
      in the health care industry in the United States. Obstetrics, as a high-volume,
      high-cost specialty, seems to have attracted considerable attention from the
      managed care industry. Wide variations in standards for treating common pregnancy
      complications as well as the keen interest expressed by regulatory agencies and
      employer groups have resulted in a variety of preventative practice and disease
      management guidelines in this field.

PMID- 8875049
TI  - Cytometry of cyclin proteins.
AB  - Cyclins are key components of the cell cycle progression machinery. They activate
      their partner cyclin-dependent kinases (CDKs) and possibly target them to
      respective substrate proteins within the cell. CDK-mediated phosphorylation of
      specific sets of proteins drives the cell through particular phases or
      checkpoints of the cell cycle. During unperturbed growth of normal cells, the
      timing of expression of several cyclins is discontinuous, occurring at discrete
      and well-defined periods of the cell cycle. Immunocytochemical detection of
      cyclins in relation to cell cycle position (DNA content) by multiparameter flow
      cytometry has provided a new approach to cell cycle studies. This approach, like
      no other method, can be used to detect the unscheduled expression of cyclins,
      namely, the presentation of G1 cyclins by cells in G2/M and of G2/M cyclins by G1
      cells, without the need for cell synchronization. Such unscheduled expression of
      cyclins B1 and A was seen when cell cycle progression was halted, e.g., after
      synchronization at the G1/S boundary by inhibitors of DNA replication. The
      unscheduled expression of cyclins B1 or E, but not of A, was also observed in
      some tumor cell lines even when their growth was unperturbed. Likewise, whereas
      the expression of cyclins D1 or D3 in nontumor cells was restricted to an early
      section of G1, the presentation of these proteins in many tumor cell lines also
      was seen during S and G2/M. This suggests that the partner kinase CDK4 (which
      upon activation by D-type cyclins phosphorylates pRB committing the cell to enter
      S) is perpetually active throughout the cell cycle in these tumor lines.
      Expression of cyclin D also may serve to discriminate G0 vs. G1 cells and, as an
      activation marker, to identify the mitogenically stimulated cells entering the
      cell cycle. Differences in cyclin expression make it possible to discriminate
      between cells having the same DNA content but residing at different phases such
      as in G2 vs. M or G2/M of a lower DNA ploidy vs. G1 cells of a higher ploidy. The
      expression of cyclins D, E, A and B1 provides new cell cycle landmarks that can
      be used to subdivide the cell cycle into several distinct subcompartments. The
      point of cell cycle arrest by many antitumor agents can be estimated with better
      accuracy in relation to these compartments compared to the traditional
      subdivision into four cell cycle phases. The latter applications, however,
      pertain only to normal cells or to tumor cells whose phenotype is characterized
      by scheduled expression of cyclins. As sensitive and specific indicators of the
      cell's proliferative potential, the cyclins, in particular D-type cyclins, are
      expected to be key prognostic markers in neoplasia.

PMID- 8875050
TI  - DiOC2(3) is not a substrate for multidrug resistance protein (MRP)-mediated drug
      efflux.
AB  - Multidrug resistance (MDR) is often related to expression of P-glycoprotein (Pgp)
      or Multidrug Resistance Protein (MRP). Pgp-mediated MDR can be evaluated by
      determining cellular retention of fluorescent substrates by flow cytometry. This
      study determined if agents used to evaluate Pgp function also can be used to
      evaluate MRP function. Cellular retention of doxorubicin (Dox), Rhodamine-123 (Rh
      123), and 3,3'-diethyloxacarbocyanine iodide (DiOC2(3)) were studied in MRP
      expressing cell lines (HL60/Adr and HT1080/DR4), whereas a Pgp expressing cell
      line (A2780/Dx5) served as a positive control. Overexpression of Pgp correlated
      inversely with retention of Dox, Rh-123, and DiOC2(3); however, under identical
      experimental conditions (1 h reincubation in drug-free medium), no retention
      difference of the three agents was detected between parental and MRP-expressing
      resistant cells. Upon extending the reincubation time to 4 h, an efflux of Rh-123
      and Dox in the resistant lines became apparent and even more pronounced after
      24h; however, still no efflux was detectable for DiOC2(3). Incubation of the
      cells with a modulator of MDR, PAK-104P, negated the observed drug efflux in Pgp
      and MRP expressing cells, which correlated with increased sensitivity of the MDR
      lines to doxorubicin. Thus both Dox and Rh-123 can be used to evaluate MRP
      function, but DiOC2(3) can not.

PMID- 8875051
TI  - Temperature-sensitive mutant p53 (ala143) interferes transiently with DNA
      synthesis and cell-cycle progression in Saos-2 cells.
AB  - It has been demonstrated that temperature-sensitive mutant p53 (val-->ala143)
      inhibits cell-proliferation at the permissive temperature, albeit to a lesser
      extent than wild-type p53 (Zhang et al.: EMBO J 13:2535-2544, 1994). We have
      studied its effect on the cell-cycle by dual-parameter flow cytometry, extended
      pulse-labeling, and pulse-chase experiments. p53ala143 interferes in Saos-2 cells
      at three levels with cell-cycle progression at permissive temperatures: it caused
      a G1-arrest, a reduced rate of DNA synthesis during S, and a prolonged G2/M.
      Strikingly, all these effects are transient. Continued culturing at 32 degrees C
      resulted in normal cell-cycle progression. Abrogation of the G1-block occurred
      even in the presence of high p21Waf1 protein levels, a negative cell-cycle
      regulator of which the expression is induced by wild-type p53.

PMID- 8875052
TI  - Toxic action of copper on the membrane system of a marine diatom measured by flow
      cytometry.
AB  - Flow cytometric measurements were used to investigate the toxic action of copper
      on some Phaeodactylum tricornutum membrane systems. Throughout the time of metal
      exposure, the percentage of viable cells decreased as copper concentration
      increased. The forward scatter signal increased as a result of copper exposure.
      After 72 h of metal exposure, cultures with 0.5 and 1 mg l-1 of copper showed an
      important increase in the peroxidase activity in comparison with control cells.
      Cells cultured with copper presented alterations in the membrane potential,
      increasing as copper concentration increased, after 96 h of metal exposure.
      Results obtained in this work showed that copper induced a degenerative process
      in P. tricornutum cells, closely related with alternations or disorders in
      membrane systems.

PMID- 8875053
TI  - Improved fetal nucleated erythrocyte sorting purity using intracellular antifetal
      hemoglobin and Hoechst 33342.
AB  - Fetal nucleated erythrocytes (FNRBC) flow sorted from maternal peripheral blood,
      using monoclonal antibodies (mAb) that bind fetal cell surface antigens, are a
      noninvasive source of fetal DNA for prenatal diagnosis. These mAbs, however, also
      bind antigens shared by maternal cells. In sorted populations, this results in
      maternal cell contamination and low fetal cell purities, which complicates
      genetic analysis by fluorescence in situ hybridization (FISH) and polymerase
      chain reaction (PCR). Fetal hemoglobin, (alpha 2 gamma 2), has been proposed as a
      useful fetal marker. To improve fetal cell enrichment from maternal blood, we
      developed an intracellular staining protocol that combines anti-gamma mAb with
      Hoechst 33342 to identify and flow sort FNRBC. Artificial mixtures of male
      umbilical cord cells (as a source of fetal hemoglobin) and female adult, non
      pregnant peripheral blood mononuclear cells were stained and flow sorted using
      this protocol. FISH analysis was performed using chromosome X and Y specific
      probes. Fetal cell purities were calculated by microscope confirmation of anti
      gamma staining and counting the number of X and Y signals present after FISH.
      Results from microscope analyses showed a fetal cell yield of 39-100% and fetal
      cell purities of 59-73%. These purities are significantly higher than the .001
      4.8% previously reported by us in maternal samples using cell surface staining
      protocols. FISH results demonstrated that 83-100% (mean = 98%) of anti-gamma
      positive cells were male, whereas 82-100% (mean = 92.5%) of anti-gamma negative
      cells were female. These results confirmed that the anti-gamma mAb is highly
      fetal specific. When applied to maternal blood samples, this protocol should lead
      to increased sensitivity for prenatal diagnosis.

PMID- 8875054
TI  - Surface antigen expression on CD34+ cord blood cells: comparative analysis by
      flow cytometry and limiting dilution (LD) RT-PCR of chymopapain-treated or
      untreated cells.
AB  - Expression of antigens coexpressed on cord blood (CB) CD34+ cells was evaluated
      by flow cytometry analysis and reverse transcriptase polymerase chain reaction
      (RT-PCR). Antigen expression was also comparatively analyzed by flow cytometry
      and limiting dilution (LD) RT-PCR to investigate effects of chymopapain on
      epitopes of several cell surface markers: LD RT-PCR allows detection of the
      expression of antigens degraded by chymopapain which are not identified by flow
      cytometry. Monoclonal antibodies (MoAbs) that recognize chymopapain resistant
      epitopes on several coexpressed cell surface markers were identified: these
      included MoAbs directed against CD11a, CD13, CD18, CD38, CD45RO, CD51, HLA-DR,
      Thy-1, c-kit, flt-3 (STK-1), and mdr-1. Interestingly, chymopapain treatment
      caused enhanced staining with MoAbs against HLA-DR, Thy-1, flt-3, mdr-1, and
      CD51. The frequency (LD RT-PCR) of CD18, CD38, Thy-1, and c-kit RT-PCR signals on
      pure sorted CD34+ CD18-, CD34+ CD38-, CD34+ Thy-1-, and CD34+ c-kit- cells,
      respectively, was similar in corresponding subsets treated or not with
      chymopapain. In contrast, the frequency of CD33 RT-PCR signals on sorted CD34+
      CD33- cells was higher in chymopapain-treated samples than in untreated samples
      and thus confirmed at the transcriptional level that the epitope recognized by
      anti-CD33 is chymopapain sensitive. Our findings extend data on the phenotypic
      profile of CB CD34+ cells and show that several key cell surface markers of
      hematopoietic progenitor cells are chymopapain resistant. In addition, the
      results of the present study demonstrate that the RT-PCR can be applied to the
      analysis of multiple RNA species in small numbers of hematopoietic progenitor
      cells and show that LD RT-PCR allows the identification and frequency
      determination of rare cells which are undetectable by flow cytometry.

PMID- 8875055
TI  - Rapid single-step method for flow cytometric detection of surface and
      intracellular antigens using whole blood.
AB  - Fixation/permeabilization methods used for the detection of intracellular
      antigens by flow cytometry often result in the destruction of cellular morphology
      and surface immunoreactivity, properties useful in flow cytometry for the
      characterization of cells in heterogeneous populations. In addition, a majority
      of these methods are incompatible with whole blood and require that peripheral
      blood leukocytes (PBLs) be purified prior to fixation. This article describes a
      new technique for the rapid detection of both intracellular and cell surface
      antigens, while preserving cell morphology, through the use of a single-step
      fixation/permeabilization reagent, ORTHO PermeaFix (OPF). OPF is compatible with
      whole blood, allowing for the direct preparation of PBLs without prior cell
      separation. An additional red blood cell lysing reagent was not required because
      RBC lysis occurred upon resuspension of OPF-treated whole blood samples in
      isotonic solution. Discrimination of leukocyte populations by light scatter after
      OPF treatment was comparable to matched unfixed live cells. In addition, absolute
      lymphocyte and white blood cell (WBC) counts were not significantly affected when
      OPF-treated cells were compared with unfixed cells. Treatment of whole blood from
      7 normal donors showed no significant difference in percentage of cells positive
      for CD2, CD3, CD4, CD8, CD16, or CD19 between fixed and unfixed samples when
      cells were stained before fixation, and no difference in CD3, CD4, CD8, CD16, or
      CD19 percentages when cells were stained following fixation. Monoclonal
      antibodies specific for intracellular antigens located at various sites within
      the cell were tested on fixed samples. OPF-treated peripheral blood lymphocytes
      showed greater than 95% reactivity for the inner mitochondrial membrane protein
      bcl-2, and the cytoskeletal cytoplasmic protein vimentin. TIA-1, a cytolytic
      granule-associated protein, showed differential reactivity within lymphocyte
      subsets, from a low of 8 +/- 2% in CD4+ cells to 89 +/- 6% in CD16+ cells, when
      whole blood from five normal donors was fixed and stained. Reh cells treated with
      OPF showed greater than 95% reactivity for the internuclear protein TdT. A
      comparison of OPF with two other fixation/permeabilization procedures, 1%
      paraformaldehyde followed by 45% ethanol and 0.25% paraformaldehyde followed by
      0.2% Tween 20, showed that only OPF could be used both prior to or following cell
      surface staining with no effect on antigen detection while allowing optimal
      detection of all of the intracellular antigens tested.

PMID- 8875056
TI  - Automatic multiparameter fluorescence imaging for determining lymphocyte
      phenotype and activation status in melanoma tissue sections.
AB  - A system has been developed that combines multiparameter fluorescence imaging and
      computer vision techniques to provide automatic phenotyping of multiple cell
      types in a single tissue section. This system identifies both the nuclear and
      cytoplasmic boundary of each cell. A routine based on the watershed algorithm has
      been developed to segment an image of Hoechst-stained nuclei with an accuracy of
      greater than 85%. Deformable splines initially positioned at the nuclear
      boundaries are applied to images of fluorescently labelled cell-surface antigens.
      The splines lock onto the peak fluorescence signal surrounding the cell,
      providing an estimate of the cell boundary. From measurements acquired at this
      boundary, each cell is classified according to antigen expression. The system has
      been piloted in biopsies from melanoma patients participating in a clinical trial
      of the antibody R24. Thin tissue sections have been stained with Hoechst and
      three different fluorescent antibodies to antigens that permit the typing and
      evaluation of activity of T-cells. Changes in the infiltrates evaluated by
      multiparameter imaging were consistent with results obtained by immunoperoxidase
      analysis. The multiparameter fluorescent technique enables simultaneous
      determination of multiple cell subsets and can provide the spatial relationships
      of each cell type within the tissue.

PMID- 8875057
TI  - DNA image cytometry on sections as compared with image cytometry on smears and
      flow cytometry in melanoma.
AB  - DNA measurements of 130 melanomas were carried out by flow cytometry (FCM) and
      image cytometry (ICM). ICM was applied to cytological preparations of fresh
      material (cICM) and to sections of formalin-fixed paraffin embedded tissue
      (sICM). The DNA ploidy, the DNA index of G0/G1 peaks (DI), and the proliferation
      index (PI) were used to compare all the methods. The following parameters
      reflecting malignancy were calculated only from ICM histograms: the 5c exceeding
      rate (5cER) and the malignancy grade (MG). In cases found to be DNA aneuploid by
      FCM, the PI values (FCM versus cICM) and the DIs (between all methods) showed a
      high correlation, and the concordance in relation to the DNA ploidy status was
      96% (FCM versus cICM) and 94% (FCM versus sICM). However, we ascertained
      essential differences between FCM and ICM in melanomas classified as DNA diploid
      by FCM. The concordance in DNA ploidy was only 66% (FCM versus cICM) and 64% (FCM
      versus sICM). In contrast, cICM and sICM yielded similar results in most cases.
      With the exception of the near diploid range, ICM is superior to FCM in detecting
      DNA aneuploidy. In particular, DNA tetraploid stem lines can easily be overlooked
      by FCM. Therefore, DNA measurements of tumours judged to be DNA diploid by FCM
      must be verified by ICM. ICM on sections proved to be applicable and yielded
      reliable results provided that a suitable thickness was used, and the measuring
      of sectioned and overlapping nuclei was largely avoided by careful focusing in
      either direction.

PMID- 8875058
TI  - Nuclear autoantigen p330d/CENP-F: a marker for cell proliferation in human
      malignancies.
AB  - p330d, also known as CENP-F, is a newly characterized cell cycle specific nuclear
      autoantigen which is associated both with the centromeres and the nuclear matrix.
      It is expressed in low amounts in G0/G1-cells and accumulates in the nuclear
      matrix during S-phase with a maximum expression in G2/M-cells. In the present
      study we have investigated if p330d/CENP-F could be used as a marker for
      proliferation in different human malignancies. A flow cytometric method was
      developed by which p330d/CENP-F expression and DNA-content could be assessed on
      hematopoietic and solid tumors. Twenty-four different human hematopoietic
      malignancies, 12 breast cancers, and several cell lines were analyzed and the
      number of p330d/CENP-F positive cells and the S-phase fraction were determined.
      The percentage of p330d/CENP-F positive cells correlated with the fraction of S
      phase cells in all human malignancies tested. Various cell lines revealed a
      similar cell cycle specific distribution. The association of p330d/CENP-F with
      the nuclear matrix facilitated the flow cytometric analysis of this protein due
      to its resistance to different preparation and fixation procedures. In summary,
      p330d/CENP-F seems to be a potentially valuable proliferation marker which can be
      applied to different tumors.

PMID- 8875059
TI  - Comparison of automated and manual analysis of interphase in situ hybridization
      signals in tissue sections and nuclear suspensions.
AB  - In this study we compared visual and automated analyses of interphase in situ
      hybridization (ISH) signals in five prostatic tumor specimens and one normal
      prostate sample, both in tissue sections and nuclear suspensions. The advantage
      of tissue sections is preservation of tissue morphology allowing precise analysis
      of tumor cells only. The advantage of nuclear suspensions is easier access to
      automated analysis, due to their disaggregated and dispersed cellular appearance.
      The samples were hybridized with probes for the (peri)centromeric regions of
      chromosome 1 and Y. The number of ISH signals per nucleus was counted both
      manually and automatically by means of a commercially available image analysis
      system. After image analysis the results were interactively corrected using a
      gallery display. The automatic and manual counts, before and after interactive
      correction, were then statistically evaluated. We found no significant
      differences in overall distributions between the automated and the manual counts,
      before as well as after correction. This was observed for both tissue sections
      and cellular suspensions. It is therefore concluded that automated analysis of
      ISH signals is feasible in both nuclear suspensions and in tissue sections,
      despite a low percentage of nuclei that could be measured on the latter.

PMID- 8875060
TI  - Comparison of Vindelov et al. and bromodeoxyuridine/DNA double-staining flow
      cytometry methods for analysis of cell cycle distribution in rat thymocytes.
AB  - This study compares the cell cycle distribution in rat thymocytes obtained by
      means of bromodeoxyuridine (BrdUrd) labeling of S-phase cells and the analysis of
      the S-phase fraction obtained according to the technique of Vindelov et al.
      (Cytometry 3:332-338, 1983). The proportion of BrdUrd-labeled cells was analyzed
      in single cell suspensions of adult rat thymocytes after in vivo injection of
      BrdUrd and the results then compared with those obtained after measuring the cell
      DNA contents according to the Vindelov et al. method. The percentage of BrdUrd
      positive cells was greater than the S-phase fraction obtained using the Vindelov
      et al. technique. By contrast, no major differences were observed between the
      percentage of BrdUrd-positive cells and the S-phase fraction obtained after
      analyzing the DNA histograms of the same data files with the RFIT mathematical
      model. The elimination of trypsin treatment used in the Vindelov et al. method
      did not alter the results, whereas the use of DNA denaturation with 2N HCl was
      shown to increase the percentage of S-phase rat thymocytes (calculated from DNA
      histograms) independently of whether trypsin treatment was used or not. However,
      the value of the S-phase fraction was not as great as that obtained after BrdUrd
      labeling. Thus when comparing BrdUrd-labeling and the Vindelov et al. technique,
      important differences in the percentage of S-phase adult rat thymocytes were
      observed. Selective G0/G1 cell loss during washing and centrifugation steps
      performed after the DNA denaturation used for BrdUrd detection was the main
      reason for these differences.

PMID- 8875061
TI  - Correction for antibody crosstalk.

PMID- 8875062
TI  - Education and the changing age pattern of American fertility: 1963-1989.
AB  - Using pooled data from the 1980, 1985, and 1990 Current Population Surveys, we
      describe fertility trends by age and education for the period 1963-1989. Interest
      focuses on whether the effects of education have changed across this period. We
      show that women with college degrees experienced dramatic shifts toward later
      ages of childbearing. This shift is consistent with arguments we develop about
      the increased opportunity for women to pursue careers and about changes in the
      availability of child care.

PMID- 8875063
TI  - The effects of temperature on human fertility.
AB  - Monthly birth and temperature data for a variety of states and countries are used
      to estimate the effect of short-run temperature fluctuations on fertility.
      Regressions of monthly births on a flexible specification of lagged monthly
      temperature show that temperature has quantitatively important effects on both
      seasonal and nonseasonal variation in births. Summer temperature extremes reduce
      conceptions in the southern United States, explaining a substantial part of the
      observed seasonal birth pattern. Extreme cold shows no evidence of affecting
      conceptions. The results also show significant seasonality in births even after
      accounting for temperature. Controls for monthly temperature do not explain the
      persistent spring peak in births in northern Europe. This finding suggests that
      other factors play an important role.

PMID- 8875064
TI  - The impact of state-level restrictions on abortion.
AB  - This research examines 23 different laws passed by state governments in an effort
      to restrict the number of abortions. It assesses both laws passed and laws
      actually enforced after the Supreme Court permitted states to restrict access to
      abortion in 1989. None of the policy actions by state governments has had a
      significant impact on the incidence of abortion from 1982 to 1992. Abortion rates
      continue to reflect past abortion rates, the number of abortion providers,
      whether the state funds abortions for Medicaid-eligible women, urbanism, and
      racial composition of the population. Recent restrictive policies have not
      affected these trends.

PMID- 8875065
TI  - Marital status and mortality: the role of health.
AB  - Prior literature has shown that married men live longer than unmarried men.
      Possible explanations are that marriage protects its incumbents or that healthier
      men select themselves into marriage. Protective effects, however, introduce the
      possibility of adverse selection: Those in poor health have incentive to marry.
      In this paper we explore the role of health in explaining mortality and marriage
      patterns, and distinguish protective effects from two types of selection effects.
      We find adverse selection on the basis of health (unhealthy men tend to (re)marry
      sooner) and positive selection on the basis of unmeasured factors that both
      promote good health and encourage marriage.

PMID- 8875066
TI  - Estimating the completeness of under-5 death registration in Egypt.
AB  - To evaluate the completeness of registration of infant and child deaths in Egypt,
      reinterviews were conducted with families who had reported a death of a child
      under age 5 in the five years before the survey for two national surveys recently
      conducted in Egypt: the United Nations PAPCHILD survey of 1990-1991 and the
      Egyptian Demographic and Health Survey (EDHS) of 1992. The survey instrument
      included questions regarding notification of the death at the local health
      bureau. If the family said the death had been notified, separate employees
      searched the health bureau records for the registration. Overall 57% of infant
      deaths were reported as notified and 68% of those death reports were found; the
      corresponding figures for child death were 89% and 74%. Using the percentage
      reported as notified as an estimate for completeness of registration, we adjusted
      upward the national infant and child mortality rates from registration data,
      giving values of 73 per 1,000 for infant mortality and 99 for 5qo for the period
      1987-1990. These values are approximately 20% above the corresponding direct
      estimates from the PAPCHILD and EDHS surveys.

PMID- 8875067
TI  - Cohort size and age-specific suicide rates: a contingent relationship.
AB  - Trends in age-specific suicide rates relate to debates about the consequences of
      population aging and changes in cohort size for social well-being. Easterlin
      argues that large cohort size increases suicide rates by reducing relative
      income; Preston claims that suicide rates fall in large cohorts with high levels
      of political and social power. To integrate these competing arguments, this paper
      uses aggregate data on 18 high-income nations from 1953 to 1986 to demonstrate
      that the direction and strength of the relationship between cohort size and
      suicide depend on (1) age of the cohort, (2) gender, (3) national context, and
      (4) time period. The results show that large cohort size raises suicide for the
      young and middle-aged, but reduces it for the elderly. Also, the effects of
      cohort size prove stronger for men than for women, for nations with less
      collectivist institutions than for nations with more collectivist institutions,
      and for the 1950s and 1960s than for the 1970s and 1980s.

PMID- 8875068
TI  - Economic opportunity in Mexico and return migration from the United States.
AB  - I analyze the influence of the economic characteristics of origin area on trip
      duration for Mexican migrants in the United States. I argue that migrants from
      economically dynamic areas in Mexico with favorable opportunities for employment
      and small capital investment have a larger incentive to stay in the United States
      longer and to withstand the psychic costs of separation from family and friends
      than do migrants from economically stagnant areas in Mexico, where the productive
      uses of savings are severely limited. In line with this argument we should expect
      investment opportunities in migrants' origin areas to be associated positively
      with migrants' trip duration in the United States. To test this hypothesis I use
      individual- and household-level data on U.S. migration experience collected in 13
      Mexican communities. Evidence from parametric hazards models supports the idea
      that economic characteristics of origin areas influence the motivations and
      strategies of Mexican migrants in the United States.

PMID- 8875069
TI  - Internal migration in China, 1950-1988.
AB  - This paper examines the long-term patterns of migration within China between 1950
      and 1988. The analysis uses data from China's 1988 2/1,000 Fertility and Birth
      Control Survey, which asks respondents about their most recent interprovincial
      move. The results suggest that long-term migration patterns can be explained by
      political and economic changes in China. We argue that the approaches we
      introduce can offer significant insight into long-term migration patterns for
      countries where historical data on migration are unavailable or unreliable.

PMID- 8875070
TI  - Reconsidering the increase in father-only families.
AB  - Previously reported estimates of rapid growth rates among father-only families
      did not account for cohabitation. An explicit treatment of cohabitation removes
      about half of the presumed growth. Nevertheless, we find that the number of
      father-only families grew at more than double the rate of mother-only families
      during the 1980s. Decomposition analyses show that the largest factor associated
      with the increase is that fathers now head a greater proportion of all formerly
      married single-parent families with children. Although the share of single-parent
      families headed by fathers is larger in 1990 than in 1980 even after controlling
      for cohabitation, it is smaller than in 1970.

PMID- 8875071
TI  - Regulation of flt-1 expression during mouse embryogenesis suggests a role in the
      establishment of vascular endothelium.
AB  - Flt-1 is a high affinity binding receptor for the vascular endothelial cell
      growth factor (VEGF) and is primarily expressed in endothelial cells. In this
      study we have investigated the temporal and spatial regulation of its expression
      by establishing mouse lines containing the lacZ gene targeted into the flt-1
      locus through homologous recombination in embryonic stem (ES) cells. In the yolk
      sac as well as in the embryo proper, lacZ expression faithfully reflected the
      endogenous expression pattern of the flt-1 gene. LacZ staining of heterozygous
      embryos led to the following observations: (1) the onset of flt-1 expression is
      detected at the early primitive streak stage in the extraembryonic mesoderm, and
      is strongly up-regulated thereafter, reaching a maximum by early to midsomite
      stages and declining subsequently; (2) while flt-1 is widely expressed within the
      developing vascular endothelium, its expression level is differentially regulated
      both spatially and temporally. The pattern of flt-1 expression suggests that it
      may play an important role in the initiation of endothelium development; and (3)
      flt-1 is expressed in essentially all the cells in early blood islands, but later
      its expression is gradually restricted to the endothelial lineage. Our results
      indicate that flt-1 is a marker for hemangioblasts, the presumed progenitor for
      both hematopoietic and angioblastic lineage. The flt-1 expression pattern also
      suggests that it may play important roles in both vasculogenesis and
      angiogenesis.

PMID- 8875072
TI  - Expression of mannose 6-phosphate receptors in chicken.
AB  - In mammals, the sorting of newly synthesized lysosomal enzymes is accomplished by
      two mannose 6-phosphate receptors (MPR) designated MPR46 and MPR300. MPR300 has
      an additional function in clearing the nonglycosylated insulin-like growth factor
      II (IGFII). The distinct expression pattern of the two MPR has been ascribed to
      the control of MPR300 expression by IGFII. In lower vertebrates, such as chickens
      or frogs, only MPR300 homologues have been described. These MPR300 homologues do
      not bind IGFII. In the present study, we examined whether lower vertebrates such
      as chickens also express two types of MPR and, if so, whether the expression
      pattern is distinct or similar. We were able to clone chicken cDNA fragments
      homologous to mammalian MPR46 and MPR300 and to show the synthesis of respective
      MPR polypeptides, thus establishing the existence of two types of MPR also in a
      nonmammalian species. Further, we analyzed the expression of the two MPR in
      chicken by Northern blotting and in situ hybridization. High levels of MPR46 and
      MPR300 RNA were detectable in epithelia, ganglia, and uropoietic system of
      chicken embryos. In a number of embryonic and adult tissues, varying ratios of
      MPR46 and MPR300 RNA were observed. The expression pattern for both MPR46 and
      MPR300 was distinct, although less pronounced than in mice. We conclude that
      functional differences unrelated to the additional function of the mammalian
      MPR300 as a receptor clearing IGFII are responsible for the distinct expression
      of the two MPR in nonmammalian, and probably also in mammalian, species.

PMID- 8875074
TI  - Transferrin and its receptor in the development of genetically determined neural
      tube defects in the mouse embryo.
AB  - The iron-binding growth factor transferrin is taken up and localised in the
      hindgut of midgestation mouse embryos. We investigated whether the distribution
      of transferrin may be disturbed in mutant curly tail embryos, a proportion of
      which exhibit a cell proliferation defect affecting the hindgut endoderm, as part
      of the pathogenetic sequence leading to development of neural tube defects.
      Immunostaining revealed a reduction in the binding and/or uptake of transferrin
      by hindgut epithelial cells in affected curly tail embryos compared with their
      unaffected littermates. There was no apparent difference between the two embryo
      types, however, in the distribution or level of expression of the transferrin
      receptor. The receptor is expressed specifically in the hindgut endoderm of the
      10.5-day embryo, although its mRNA is present in all tissues of the posterior
      neuropore region, suggesting posttranscriptional control of gene expression.
      These findings may indicate a role for transferrin binding and/or uptake in the
      regulation of cell proliferation in the hindgut endoderm, with a defect in this
      process in the curly tail mutant. However, an alternative explanation is
      suggested by our finding that transferrin immunostaining is more intense in the
      hindgut of unaffected curly tail embryos than in nonmutant CBA/Ca and CD-1
      embryos. Thus, mutant embryos may increase their uptake of transferrin in an
      attempt to compensate for defective cell proliferation in the hindgut resulting
      from a defect in another pathway. Only a proportion of embryos are able to mount
      this compensatory response leading to the observed partial penetrance of
      developmental defects in the curly tail mutant mouse.

PMID- 8875073
TI  - Expression of avian glypican is developmentally regulated.
AB  - An avian cDNA homologue of human and rat glypicans has been cloned from a stage
      17 chicken heart cDNA library and used to analyze the distribution of this
      proteoglycan during development by Northern analysis and whole mount in situ
      hybridization. At stages 7-12, strong signals were detected in the cephalic
      region of the neural folds, rostral portion of paraxial mesoderm, and newly
      formed epithelial somites. At stages 20-25, strong expression was observed in the
      mantle zone of the telencephalon, the apical epidermal ridge and proximal region
      of developing limb. Transcripts also were found in the truncus arteriosus and
      arteriovenous-canal region of the heart, but not in the myocardium. This
      distribution pattern suggests that the avian glypican may be involved in the
      morphogenesis of limb, somite, heart, and brain. The expression of glypican also
      overlaps FGFs in limb bud, FGF receptors in heart and somite, and NGF receptors
      in forebrain. The affinity of heparan sulfate proteoglycans for growth factors
      and the distribution of the avian glypican are consistent with a role for this
      molecule in growth factor-mediated signals.

PMID- 8875075
TI  - Retinoic acid alters the expression of pattern-related genes in the developing
      rat lung.
AB  - Exogenous retinoids alter pattern formation and differentiation in many
      developing systems, such as limb, vertebrae, and central nervous system. Many of
      these effects are mediated by changes in expression of patterning genes such as
      Hox genes and Sonic hedgehog. We have previously shown that exogenous retinoic
      acid, administered to the embryonic rat lung in culture alters the structural
      pattern of the developing lung, suppressing formation of distal lung and favoring
      growth of proximal tubules. To determine whether these retinoic acid-induced
      changes in lung development were linked to alterations in pattern-related genes,
      we characterized the expression of Hoxa-2, Hoxb-6, and Sonic hedgehog mRNAs in
      vivo and in vitro, with or without 10(-5)M retinoic acid, by in situ
      hybridization and quantitative polymerase chain reaction. Each of these genes
      demonstrated unique timing and distribution of expression that was similar in
      vivo and in control cultured embryonic lungs. Hoxb-6 and Sonic hedgehog mRNAs
      both decreased during lung development in vivo or in vitro. From the patterns of
      mRNA expression we propose that Hoxb-6 is involved in distal airway branching
      while Hoxa-2 is involved in differentiation of proximal mesenchymal derivatives
      and vasculogenesis in the lung. RA upregulated all three genes, changing their
      developmental pattern of distribution and preventing the developmental decrease
      in Sonic hedgehog expression. We propose that RA acts to maintain high levels of
      expression of these and likely other pattern-related genes in a fashion that is
      characteristic of the immature lung, promoting continued formation of proximal
      lung structures and preventing formation of typical distal lung structures of the
      mature lung.

PMID- 8875076
TI  - Analysis of MyoD, myogenin, and muscle-specific gene mRNAs in regenerating
      Xenopus skeletal muscle.
AB  - We have analyzed in adult Xenopus laevis, using in situ hybridization, the
      spatial and temporal expression patterns of MyoD, myogenin, and alpha-skeletal
      actin and fast myosin heavy chain mRNAs during muscle regeneration following
      cardiotoxin injury. MyoD transcripts could be detected in the satellite cells as
      early as the first stage of regeneration and were expressed persistently
      throughout the regeneration process. Myogenin mRNAs were transiently expressed in
      forming myotubes. alpha-Skeletal actin and fast myosin heavy chain mRNAs were
      detected precociously, before the young myotube stage. This work has shown, for
      the first time, the presence of myogenin transcripts during Xenopus myogenesis.

PMID- 8875077
TI  - Immunolocalization of osteonectin in avian tibial dyschondroplastic cartilage.
AB  - Osteonectin is an acidic calcium-binding protein found in cartilage, bone matrix,
      vascular endothelium, and areas of tissue repair. Using immunocytochemistry,
      osteonectin has been localized in all zones of the normal avian epiphyseal growth
      plate with notably high amounts in the hypertrophic zone. In the proximal portion
      of this zone the staining was intracellular, while in the distal calcifying
      portion of the hypertrophic zone staining was both intracellular and
      extracellular. Osteonectin was also detected in the growth plate associated with
      lesions of chickens with tibial dyschondroplasia (TD). Intense intracellular
      staining was observed in hypertrophic chondrocytes proximal to the lesion;
      staining was markedly diminished in the TD lesion; extracellular matrix was
      devoid of staining. Staining intensity was high along the peripheral edges of the
      lesion that were undergoing vascularization and resorption. This was the only
      area in the dysplastic cartilage where staining was observed in the extracellular
      matrix as well as intracellularly. Similar patterns were viewed in all TD lesions
      examined, whether they were spontaneous or induced by dietary treatments or
      genetic selection.

PMID- 8875078
TI  - Spatial and temporal activity of the alpha B-crystallin/small heat shock protein
      gene promoter in transgenic mice.
AB  - In order to study the spatial and temporal activity of the mouse alpha B
      crystallin/small heat shock gene promoter during embryogenesis, we generated mice
      harboring a transgene consisting of approximately 4 kbp of alpha B-crystallin
      promoter sequence fused to the Escherichia coli lacZ reporter gene. beta
      galactosidase activity was first observed in the heart rudiment of 8.5 days post
      coitum (d.p.c.) embryos. An identical expression pattern was obtained for the
      endogenous alpha B-crystallin gene by whole mount in situ hybridization. At 9.5
      d.p.c., beta-galactosidase activity was detected in the lens placode, in the
      myotome of the somites, in Rathke's pouch (future anterior pituitary), and in
      some regions of oral ectoderm. We also examined the stress inducibility of the
      alpha B-crystallin promoter in vivo. Injection of sodium arsenite into mice
      resulted in increased endogenous alpha B-crystallin expression in the adrenal
      gland and possibly the liver. Our results indicate that visualization of beta
      galactosidase activity provides an accurate reflection of endogenous alpha B
      crystallin expression and demonstrate that the complex developmental pattern of
      mouse alpha B-crystallin gene expression is regulated at the transcriptional
      level. This expression pattern, coupled with the present literature which
      addresses functions of the protein, suggests a role for the alpha B
      crystallin/small heat shock protein in intermediate filament turnover and
      cellular remodeling which occur during normal development and differentiation.

PMID- 8875079
TI  - Expression of the beta 4 integrin subunit in the mouse heart during embryonic
      development: retinoic acid advances beta 4 expression.
AB  - Using immunohistochemical techniques as well as in situ hybridization we were
      able to elicit the expression pattern of the beta 4 integrin subunit in the
      murine heart during development. We show that beta 4 is not expressed in the
      heart before E13 and is afterwards restricted to the endocardium of the
      atrioventricular canal, the outflow tract, and the venous valves in the right
      atrium. As these are all sites of high shear stress in the heart, we propose a
      role for alpha 6 beta 4 in the tight adhesion of the endocardial cells to their
      basement membranes in these segments. Moreover, mouse embryos were treated with
      all-trans retinoic acid, which was previously shown to induce congenital
      malformations, among which malformations of the heart. We show an advanced
      expression without ectopic localization of cardiac beta 4 after the
      administration of retinoic acid. This advanced appearance of beta 4 was also
      shown in extracardiac tissue like migrating neural crest cells. Several
      hypotheses on the mechanism of beta 4 up-regulation and a possible role for alpha
      6 beta 4 in the development of heart malformations after the administration of
      retinoic acid are discussed.

PMID- 8875080
TI  - Tight junctions in early amphibian development: detection of junctional cingulin
      from the 2-cell stage and its localization at the boundary of distinct membrane
      domains in dividing blastomeres in low calcium.
AB  - Although functional studies indicate that tight junctions (TJ) are present in
      Xenopus laevis embryos from the 2-cell stage onward, morphological studies have
      failed to identify typical TJ structures before the 32-cell stage. Nothing is
      known about the expression and localization of TJ proteins in early Xenopus
      development. Here we have investigated the formation and composition of TJ in
      developing Xenopus embryos by whole-mount immunoperoxidase staining of
      eggs/embryos and immunoblotting of extracts with an antiserum against the TJ
      protein cingulin. Immunoblot analysis of eggs and embryo extracts showed that the
      antiserum labeled a major polypeptide of apparent M(r) 160 kD. Maternal cingulin
      was distributed diffusely in the cytocortical region of eggs and early embryos.
      Intense cingulin labeling became localized in the junctional region starting from
      the first cell division (2-cell stage). During cytokinesis, cingulin labeling was
      accumulated into new junctions in a precise spatial/temporal relationship with
      the deepening of the cleavage furrow. In semithin sections of stained embryos,
      labeling was detected in the most apical portion of the region of cell-cell
      contact. In embryos incubated in low calcium medium for 30 min, newly divided
      blastomeres failed to completely adhere to each other. However, cingulin labeling
      was accumulated along a linear structure that was at the border between distinct
      membrane domains (apical and lateral). These observations provide the first
      description of assembly of a TJ protein at the earliest stages of Xenopus
      development and suggest that TJ occur from the 2-cell stage onward and are
      assembled with maternal stores of protein. The formation of cingulin-containing
      structures even when lateral cell-cell adhesion is greatly reduced suggests that
      the apical cytocortex may have a determinative influence on TJ assembly and
      establishment of cell polarity.

PMID- 8875081
TI  - Inhibition of in vitro limb cartilage differentiation by syndecan-3 antibodies.
AB  - The transmembrane heparan sulfate proteoglycan syndecan-3 is transiently
      expressed in high amounts during the cellular condensation process that
      characterizes the onset of limb cartilage differentiation. During condensation,
      limb mesenchymal cells become closely juxtaposed and undergo cell-cell and cell
      matrix interactions that are necessary to trigger cartilage differentiation and
      cartilage-specific gene expression. To test directly the possible involvement of
      syndecan-3 in regulating the onset of limb chondrogenesis, we examined the effect
      of polyclonal antibodies against a syndecan-3 fusion protein on the chondrogenic
      differentiation of chick limb mesenchymal cells in micromass culture. Syndecan-3
      antiserum elicits a dose-dependent inhibition of the accumulation of Alcian blue
      stainable cartilage matrix by high density limb mesenchymal cell micromass
      cultures (2 x 10(5) cells/10 microliters) and a corresponding reduction in steady
      state levels of mRNAs for cartilage-characteristic type II collagen and the core
      protein of the cartilage proteoglycan aggrecan. In preimmune serum-treated
      control cultures proliferating cells are limited to the periphery of areas of
      cartilage matrix deposition, whereas large numbers of proliferating cells are
      uniformly distributed throughout the undifferentiated cultures supplemented with
      syndecan-3 antiserum. Limb mesenchymal cells cultured at lower densities (1 x
      10(5) cells/10 microliters) in the presence of preimmune serum form extensive
      precartilage condensations characterized by the close juxtaposition of rounded
      cells by day 2 of culture. In contrast, in the presence of syndecan-3 antiserum,
      the cells fail to aggregate but rather remain flattened and spatially separated
      from one another, suggeting that syndecan-3 antibodies impair the formation of
      precartilage condensations. These results indicate that syndecan-3 plays an
      important role in regulating the onset of limb chondrogenesis, perhaps by
      mediating the cell-cell and cell-matrix interactions required for condensation
      and subsequent cartilage differentiation.

PMID- 8875082
TI  - Diabetes complications in NIDDM kindreds linked to the MODY3 locus on chromosome
      12q.
AB  - OBJECTIVE: To assess the prevalence of diabetes complications and the severity of
      diabetes in kindreds with NIDDM linked to the MODY3 locus (chromosome 12q) and to
      compare these parameters with data obtained in glucokinase (GCK)-deficient and
      other-MODY (unlinked to any of the three known loci) families, as well as with
      data from families with a late age of onset of NIDDM. RESEARCH DESIGN AND
      METHODS: Clinical and biological data were obtained from 667 affected members of
      7 MODY3, 25 GCK-deficient, 6 other-MODY, and 81 NIDDM families. Severity of
      diabetes (glucose tolerance status and insulin secretion) was assessed by an oral
      glucose tolerance test. Neurological examination and eye fundus examination were
      performed in 349 and 251 subjects, respectively, and proteinuria was tested with
      strips in 282 family members. RESULTS: A higher prevalence of proliferative
      retinopathy was observed in MODY3 (21%) and NIDDM subjects (23%) than in GCK
      deficient (3%) and other-MODY subjects (8%; P = 0.004). Proteinuria was detected
      in 19, 7, 5, and 0% (P = 0.07) of subjects, respectively. Prevalence of
      neuropathy was higher in NIDDM (17%; P = 0.005) than in MODY3 (4%), GCK-deficient
      (5%) and other-MODY (0%) subjects. MODY3 and NIDDM subjects had significantly
      higher fasting glucose levels than subjects in the other groups. Glucose levels
      after 2 h were significantly higher, and the ratios of insulin to glucose levels
      were significantly lower in MODY3 subjects than in the other three groups.
      CONCLUSIONS: The MODY3 subtype of NIDDM is characterized by a severe insulin
      secretory defect and by major hyperglycemia that progresses rapidly to overt
      diabetes. Microvascular complications of diabetes were frequently observed in the
      MODY3 subjects and the subjects with a late age of onset of NIDDM in this cohort.
      Both the duration and the severity of diabetes were independently associated with
      these complications.

PMID- 8875083
TI  - The effect of metformin on the metabolic abnormalities associated with upper-body
      fat distribution. BIGPRO Study Group.
AB  - OBJECTIVE: The constellation of anomalies associated with insulin resistance is a
      plausible additional cause of ischemic cardiovascular disease and of NIDDM. To
      test this hypothesis in a primary prevention trial, the effects of metformin as a
      potential candidate for intervention in the insulin resistance syndrome (IRS)
      were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH
      DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to
      hip ratio. They were randomly allocated to receive either metformin or placebo,
      following a double-blind procedure. After 1 year of treatment, the main clinical
      and biological parameters of the IRS were assessed and their evolution compared
      between treatment groups. RESULTS: Compared with placebo, metformin induced a
      significant weight loss, a better maintenance of fasting blood glucose, total and
      LDL cholesterol levels, and a greater decrease of fasting plasma insulin
      concentration. Moreover, tissue-type plasminogen activator antigen, a marker of
      fibrinolytic impairment, showed a significant decrease under metformin. By
      contrast, metformin treatment had no significant effect on blood pressure or
      serum triglyceride and HDL cholesterol concentrations. The main side effect of
      metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in
      Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate
      for long-term intervention for the prevention of diabetes but that its use in a
      trial of primary prevention of cardiovascular diseases requires either a
      reevaluation of its properties toward the most potentially atherogenic anomalies
      of the IRS or a better definition of the target population.

PMID- 8875084
TI  - A comprehensive assessment of the avoidability of long-term complications of
      diabetes. A case-control study. SID-AMD Italian Study Group for the
      Implementation of the St. Vincent Declaration.
AB  - OBJECTIVE: To identify and quantify risk factors for the development of long-term
      diabetic complications (i.e., critical limb ischemia, amputation, chronic renal
      failure [creatinine > 3 mg/dl], dialysis treatment, proliferative retinopathy,
      blindness), with particular emphasis on those variables that, being related to
      quality of care, can be considered avoidable. RESEARCH DESIGN AND METHODS: We
      designed a case-control study that enrolled 886 patients with long-term diabetic
      complications and 1,888 control subjects without complications from 35 diabetic
      outpatient clinics and 49 general practitioners offices during a 6-month period.
      Selected socioeconomic, pathophysiologic, self-care, health care, and lifestyle
      information were collected for all patients. RESULTS: A logistic regression
      analysis showed that several factors are related to the development of major
      diabetic complications. Among patient characteristics, male sex (odds ratio [OR]
      = 1.8, 95% CI 1.4-2.3) and age (OR = 1.7, 95% Cl 1.2-2.4 for patients between 50
      and 69 years of age as opposed to those younger than 50 years of age) were
      associated with an increased risk of complication. Among clinical variables, the
      type and the duration of diabetes were the most important predictors of diabetic
      complications. The presence of hypertension was also associated with the
      development of diabetic complications, particularly when it was poorly controlled
      by treatment (OR = 3.1, 95% CI 2.3-4.3). Patients who needed help to reach a
      health care facility and those who did not regularly attend such a facility were
      at higher risk of developing complications (OR = 1.5, 95% CI 1.2-1.9; OR = 1.7,
      95% CI 1.3-2.2, respectively). Educational aspects were also related to the
      outcome: patients who did not receive any kind of educational intervention had an
      increased risk of developing complications (OR = 4.1, 95% CI 1.7-9.7), while self
      management of insulin therapy had a protective effect (OR = 0.6, 95% CI 0.5-0.8).
      The summary attributable risk related to avoidable risk factors (i.e.,
      uncontrolled hypertension, poor compliance with visit scheduling, inadequate
      diabetes education, no self-management of insulin treatment) was 0.39.
      CONCLUSIONS: Our data suggest that, by removing avoidable risk factors, the
      number of diabetic complications considered could be reduced by more than one
      third. The case-control methodology represents an efficient way of monitoring
      clinical practice and relating it to important outcomes. It can be of help for
      policy makers in identifying the more effective strategies and in tailoring
      specific interventions aimed at improving the quality of the care delivered to
      diabetic patients.

PMID- 8875085
TI  - Metformin improves hemodynamic and rheological responses to L-arginine in NIDDM
      patients.
AB  - OBJECTIVE: The endothelium plays a pivotal role in the regulation of vascular
      tone by releasing nitric oxide (NO). Increased availability of L-arginine, the
      natural precursor of NO, induces vasodilatation and inhibits platelet activity.
      We studied the effect of metformin on hemodynamic and rheological responses to L
      arginine in patients with NIDDM. RESEARCH DESIGN AND METHODS: Ten newly diagnosed
      NIDDM patients with mild fasting hyperglycemia (7.5 +/- 0.3 mmol/l) and without
      evidence of both micro- and macrovascular complications were investigated. They
      received an intravenous infusion of L-arginine (1 g/min for 30 min) with
      evaluation of plasma glucose and insulin, systolic (sBP) and diastolic (dBP)
      blood pressure, heart rate and plasma catecholamines, platelet aggregation, and
      blood viscosity and filterability. The L-arginine test was repeated after an 8
      week treatment with metformin (850 mg b.i.d.). RESULTS: Metformin treatment
      significantly reduced basal fasting plasma glucose, HbA1c, and platelet
      aggregation to ADP (P < 0.05); the other parameters did not change. During
      pretreatment test, L-arginine infusion decreased sBP (from 137 +/- 4.1 to 129 +/-
      4.5 mmHg, P < 0.01) and dBP (from 79 +/- 1.9 to 75 +/- 1.2 mmHg, P < 0.01)
      without affecting heart rate or plasma catecholamines. Both platelet aggregation
      and blood viscosity showed significant decrements after L-arginine, while blood
      filterability did not change. After metformin treatment, the decrease in blood
      pressure after L-arginine infusion was significantly enhanced, with a maximal
      decrease of sBP of 12 +/- 3.4 mmHg (8 +/- 2.5 mmHg pretreatment, P < 0.05) and
      dBP of 9.5 +/- 2.4 mmHg (4.5 +/- 1.9 mmHg pretreatment, P < 0.01). Heart rate,
      plasma norepinephrine levels, and blood filterability also rose significantly (P
      < 0.05-0.01). The decrease in both platelet aggregation and blood viscosity after
      L-arginine was significantly amplified after metformin. CONCLUSIONS: We conclude
      that L-arginine infusion in newly diagnosed NIDDM patients without vascular
      complications produces relevant hemodynamic and theological changes, which are
      amplified by an 8-week treatment with metformin. Whether these vascular effects
      of metformin will improve the poor cardiovascular outlook of the diabetic patient
      is still unknown.

PMID- 8875086
TI  - Decreased serum 1,5-anhydroglucitol in nondiabetic subjects with a family history
      of NIDDM.
AB  - OBJECTIVE: To investigate the effect of a family history of NIDDM on HbAlc and
      serum 1,5-anhydroglucitol (AG) in nondiabetic subjects. RESEARCH DESIGN AND
      METHODS: A 75-g oral glucose tolerance test was performed; 258 subjects with
      normal glucose tolerance and 106 subjects with impaired glucose tolerance (IGT)
      were selected HbAlc and serum AG were compared between subjects with and without
      a family history of NIDDM. The relationships between age, BMI, HbAlc, serum AG,
      fasting and 2-h plasma glucose, and urinary glucose were also examined using
      principal component analysis with a varimax rotation. RESULTS: In the normal
      group, only serum AG was lower in subjects with a positive family history than in
      those with no family history. On the other hand, in the IGT group, subjects with
      a positive family history were younger and had a higher 2-h plasma glucose, a
      higher urinary glucose, and a lower serum AG than those with no family history,
      whereas there was no difference in HbAlc. Principal component analysis identified
      three factors. The first factor, a linear combination of HbAlc and fasting plasma
      glucose, was labeled an average glycemic factor. The second factor, which
      included serum AG, 2-h plasma glucose, and urinary glucose, was labeled an
      oscillatory glycemic factor. The third factor, which contrasted age against BMI,
      was labeled an environmental factor. CONCLUSIONS: Serum AG is related to
      glycosuria even among nondiabetic subjects, and its concentrations are decreased
      in those with a family history of NIDDM. Our results suggest that serum AG rather
      than HbAlc reflects early metabolic abnormalities in these subjects.

PMID- 8875087
TI  - Effects of the short-acting insulin analog [Lys(B28),Pro(B29)] on postprandial
      blood glucose control in IDDM.
AB  - OBJECTIVE: To establish the effects of the short-acting insulin analog Lispro
      versus human regular insulin (Hum-R) on postprandial metabolic control in IDDM.
      RESEARCH DESIGN AND METHODS: Four studies were performed in 10 C-peptide-negative
      IDDM patients. Lispro or Hum-R (0.15 U/kg) or Lispro + NPH (0.07 U/kg) or Hum-R +
      NPH were injected subcutaneously 30 min (Hum-R) or 5 min (Lispro) before lunch.
      Preprandial plasma glucose (PG) was maintained on all four occasions at
      approximately 7.3 mmol/l by intravenous insulin. RESULTS: After subcutaneous
      Lispro injection, plasma free insulin (FIRI) was greater between 0 and 2 h (233
      +/- 22 pmol/l) than after Hum-R (197 +/- 25 pmol/l) but lower between 2.25 and 7
      h (81 +/- 10 vs. 104 +/- 13 pmol/l, P < 0.05). After Lispro, PG was lower versus
      Hum-R for 3 h (7.4 +/- 0.6 vs. 8.3 +/- 0.9 mmol/l) but subsequently increased
      more than after Hum-R (3.25-7h, 11.3 +/- 1 vs. 9.6 +/- 1.2 mmol/l), resulting in
      a 7-h postprandial PG greater than Hum-R (9.4 +/- 0.5 vs. 8.8 +/- 0.6 mmol/l)
      (all P < 0.05). Addition of NPH to Lispro increased the 2.5-to 7-h FIRI to 110 +/
      11 pmol/l and decreased the 3.25- to 7-h PG to 7.7 +/- 0.8 pmol/l, resulting in
      0- to 7-h PG (7.3 +/- 0.3 mmol/l) lower than after Hum-R + NPH (7.9 +/- 0.5
      pmol/l) (P < 0.05). CONCLUSIONS: At meals, in order for Lispro to improve
      postprandial blood glucose not only at 2-h, but also over a 7-h period in C
      peptide-negative IDDM, basal insulin must be optimally replaced.

PMID- 8875088
TI  - The metabolic syndrome in Hong Kong Chinese. The interrelationships among its
      components analyzed by structural equation modeling.
AB  - OBJECTIVE: To examine the pattern of the metabolic syndrome in Chinese and the
      causal relationships among its components, including aging, obesity,
      hyperglycemia, hypertension, hypertriglyceridemia, and hyperinsulinemia in these
      subjects. RESEARCH DESIGN AND METHODS: Based on a 75-g oral glucose tolerance
      test, the World Health Organization criteria were used for the diagnosis of
      glucose intolerance in a population-based study involving 1.513 Chinese subjects
      in two work sites. Demographic data including age, family history of diabetes,
      BMI, waist-to-hip ratio (WHR), and sitting blood pressure (BP) were documented.
      Fasting plasma glucose, triglyceride (TG) and insulin concentrations, and spot
      urinary albumin concentration (Ualb) were also measured. Structural equation
      modeling incorporating factor analysis and path analysis was performed to examine
      the causal relationships among these variables and their interactions. RESULTS:
      Subjects who were treated with antidiabetic and/or antihypertensive drugs or who
      had a plasma creatinine level > or = 150 mumol/l were excluded (n = 52). The
      prevalence of diabetes and impaired glucose tolerance (IGT) were 3.9% (n = 34)
      and 7.2% (n = 63) in men (n = 881) and 3.1% (n = 18) and 6.7% (n = 39) in women
      (n = 580), respectively. In both groups, glucose intolerance was associated with
      increasing age, higher BMI, WHR, BP, Ualb, serum TG, and insulin levels as well
      as higher prevalence rates of positive family history of diabetes. Structural
      equation modeling showed that age was a significant determinant for both BMI and
      WHR. Age and obesity accounted for most of the variance of BP, Ualb, plasma
      glucose, insulin and TG levels either directly or indirectly. Plasma glucose was
      determined by a positive family history of diabetes, age, and BMI while TG was
      dependent on BMI and WHR. Serum insulin was mainly determined by a positive
      family history of diabetes, obesity, plasma glucose, and TG levels. Apart from
      age and obesity, BP was also determined by serum insulin, both of which had
      causal effects on Ualb. CONCLUSIONS: This model emphasizes the centrality of
      aging and obesity as well as a positive family history of diabetes as major
      determinants of the components of the metabolic syndrome. These components in
      turn had causal effects upon one another. Apart from a familial tendency, a
      central neurohormonal mechanism may account for these abnormalities mediated
      primarily through obesity and in close association with aging.

PMID- 8875089
TI  - Impact of disease duration on cardiovascular and pupillary autonomic nervous
      function in IDDM and NIDDM patients.
AB  - OBJECTIVE: To determine the age-independent impact of disease duration on
      autonomic nervous function in diabetic patients and to compare it with other
      disease-related complications. RESEARCH DESIGN AND METHODS: Of the patients with
      diabetes, 166 (66 IDDM, 100 NIDDM) were investigated using standardized
      cardiovascular and pupillary test procedures, which provide 10 age-independent
      percentile values for each patient. Sensorimotor neuropathy was assessed using a
      standardized clinical examination, retinopathy by fundoscopy, and nephropathy
      using daily urinary protein excretion and creatinine clearance. RESULTS: The
      duration of the disease did not correlate with the results of any one of six
      standard cardiovascular tests (P > 0.15). Pupillary parameters showed a weak
      negative correlation with disease duration (P < 0.04). Prevalence of
      cardiovascular autonomic dysfunction was not different in five different
      subgroups subdivided according to disease duration (0-6, 7-12, 13-18, 19-24, and
      > or = 25 years), whereas prevalence of pupillary dysfunction changed
      significantly with disease duration (P = 0.016). In contrast, the prevalence of
      sensorimotor neuropathy (P = 0.006), retinopathy (P < 0.001), and proteinuria (P
      = 0.010) was significantly higher in patients with long-standing disease. Disease
      duration was not significantly different in patients without overall
      cardiovascular dysfunction, as compared with patients with dysfunction (15.6 +/-
      1.0 vs. 16.5 +/- 1.5 years, P = 0.626). This was also found when considering
      overall pupillary dysfunction (14.5 +/- 1.4 vs. 17.2 +/- 1.0 years, P = 0.125).
      CONCLUSIONS: Disease duration was not correlated with cardiovascular autonomic
      nervous function, whereas a correlation was observed with pupillary autonomic
      nervous function, sensorimotor neuropathy, retinopathy, and proteinuria. This may
      indicate that cardiovascular autonomic nervous function does not markedly change
      during the course of the disease. The question arises whether cardiovascular
      autonomic neuropathy may be more a functional abnormality than a structural
      lesion of the autonomic nervous system, which may be already present at the
      beginning, or even before, the manifestation of diabetes.

PMID- 8875090
TI  - Familial aggregation of medial arterial calcification in Pima Indians with and
      without diabetes.
AB  - OBJECTIVE: Little is known about medial arterial calcification (MAC) other than
      its association with age, sex, diabetes, and diabetes complications. Familial
      aggregation of this disorder was studied to determine the importance of potential
      genetic factors and to assess whether such familial aggregation was independent
      of that of diabetes. RESEARCH DESIGN AND METHODS: Members of 1,256 Pima Indian
      nuclear families with 3,339 offspring were examined radiologically for MAC of the
      feet. Multiple logistic regression analyses were used to compare the presence of
      the disorder in a parent with the presence of MAC in an offspring and to
      determine whether familial aggregation of MAC was independent of parental
      diabetes. RESULTS: Controlled for age, sex, diabetes, serum cholesterol, and
      blood pressure, offspring of one parent with MAC had 3.3 (95% CI 1.5-7.6) times
      the odds of MAC as did offspring of parents without MAC, and offspring with both
      parents affected had an even higher risk (odds ratio, 8.1; 95% CI 3.4-18.8).
      Controlled for offspring age and sex and for parental age and diabetes, parental
      MAC was associated with the disorder in offspring (P < 0.001), but the effect of
      parental diabetes on MAC in the offspring was not significant when controlled for
      parental MAC (P = 0.36). Furthermore, offspring of nondiabetic parents with MAC,
      controlled for age, sex, diabetes, and diabetes duration, had 1.7 (95% CI 0.9
      3.1) times the odds of MAC than did offspring of diabetic parents with MAC.
      CONCLUSIONS: Independent of parental age and diabetes and offspring age, sex,
      diabetes, and diabetes complications, parental MAC confers an increased risk of
      MAC in offspring. These findings suggest that the factors responsible for the
      familial clustering of MAC may be different from those for diabetes.

PMID- 8875091
TI  - A two-step strategy for identification of high-risk subjects for a clinical trial
      of prevention of NIDDM.
AB  - OBJECTIVE: To evaluate 2-h plasma glucose (2HPG), fasting plasma glucose (FPG),
      glycosylated hemoglobin (HbA1), a combination of FPG and HbA1 (FPG-HbA1), and
      other factors as screening tests for identifying high-risk subjects for a
      clinical trial of prevention of NIDDM and to identify strategies to minimize the
      total number of oral glucose tolerance tests (OGTTs) required to recruit eligible
      subjects to the trial. RESEARCH DESIGN AND METHODS: One thousand, one hundred and
      eight nondiabetic Pima Indians aged 25-64 years were followed for up to 5 years,
      and factors predicting NIDDM, defined by World Health Organization criteria (2HPG
      > or = 11.1 mmol/l), were assessed using Cox's proportional hazards analysis.
      Various threshold values of FPG, HbA1, and FPG-HbA1 were determined, which, when
      combined with an OGTT, identified subjects with impaired glucose tolerance (IGT)
      (2HPG > or = 7.8 and < 11.1 mmol/l) at a number of specified risks for developing
      NIDDM in 5 years. The value of each of the three tests was then assessed by
      calculating (for each threshold) the numbers to be screened, the numbers
      requiring an OGTT, and the sample size of IGT subjects needed to detect a 33%
      reduction in NIDDM by an experimental intervention at a power of 80%. RESULTS:
      During a median of 4.3 years of follow-up, 91 (8.2%) of the 1.108 nondiabetic
      subjects developed NIDDM. The estimated 5-year cumulative incidence rate was
      13.5%. Each of the variables, 2HPG, FPG, HbA1, FPG-HbA1, BMI, IGT, and systolic
      (sBP), diastolic (dBP), and mean (MBP) blood pressures, predicted NIDDM (P < 0.05
      for each) when controlled for age and sex. In a stepwise proportional hazards
      analysis model, 2HPG and FPG-HbA1 (P < 0.001 for each) were selected as the best
      set of predictors of NIDDM and of fasting hyperglycemia (FPG > or = 7.8 mmol/l).
      CONCLUSIONS: A two-step strategy, in which high-risk individuals are first
      identified by FPG or FPG-HbA1 and then the OGTT is used to select subjects with
      IGT, requires fewer OGTTs than when using 2HPG as the initial screening test
      without substantially increasing the numbers that would need to be screened. Such
      a strategy also offers the advantage of reducing the necessary sample size and is
      therefore an effective, efficient, and convenient method of identifying eligible
      subjects for a clinical trial of prevention of NIDDM.

PMID- 8875092
TI  - Insulin antibodies do not preclude optimization of metabolic control in women
      with IDDM during pregnancy.
AB  - OBJECTIVE: To evaluate whether the presence of insulin antibodies (IAs) may
      preclude the optimization of metabolic control during pregnancy and affect
      outcome in women with IDDM. RESEARCH DESIGN AND METHODS: IAs were measured by
      radiobinding assay in 44 women with IDDM referred to the Diabetes and Pregnancy
      Outpatients' Clinic during 46 pregnancies. Age, duration of IDDM, metabolic
      control (HbA1c, mean pre- and postprandial capillary blood glucose, frequency of
      hypo- or hyperglycemia), insulin requirement at 1st and 3rd trimester of
      pregnancy, BM1, and weight gain were recorded. Neonatal variables such as
      gestational age, weight, length, and the presence at birth of either
      hypoglycemia, hypocalcemia, or jaundice requiring phototherapy were also
      considered. RESULTS: IAs correlated positively with insulin requirement (P <
      0.05) and negatively with HbA1c at term (P < 0.01). Patients with IA levels > or
      = 40% insulin binding (8 of 46) had a higher insulin requirement and lower
      preprandial capillary blood glucose at the beginning of pregnancy but not at term
      (P < 0.005), whereas they had lower HbA1c at term than did patients with low IA
      levels (P < 0.01). IA levels decreased slightly at term (P = 0.007). IA levels >
      or = 40% were not associated with a higher rate of hypo- or hyperglycemic
      episodes or with diabetic complications or thyreopathy. No correlation was found
      between 1A levels and any of the neonatal variables considered. CONCLUSIONS: The
      presence of IAs does not preclude optimization of metabolic control during
      pregnancy and is compatible with a favourable outcome.

PMID- 8875093
TI  - Seven-year changes in body fat and visceral adipose tissue in women. Association
      with indexes of plasma glucose-insulin homeostasis.
AB  - OBJECTIVE: To study the associations between changes in body fatness, visceral
      adipose tissue (AT), and indexes of plasma glucose-insulin homeostasis over a 7
      year follow-up period. RESEARCH DESIGN AND METHODS: A sample of 30 nondiabetic
      women aged 35.2 +/- 5.6 (SD) years at baseline was studied. RESULTS: Changes in
      visceral AT and in subcutaneous AT (measured by computed tomography) as well as
      changes in body fat mass (obtained by hydrostatic weighting) were significantly
      related to changes in fasting plasma insulin levels and in plasma insulin area
      measured after a 75-g oral glucose load (0.47 < or = r < or = 0.62; P < 0.01).
      Changes in visceral AT but not in body fat mass or in subcutaneous AT area were
      significantly associated with changes in plasma glucose area (r = 0.37; P <
      0.05). When two subgroups of women with similar mean increases in body fat mass
      but with either small or large increases in visceral AT were compared, the
      subgroup with the largest gain in visceral AT showed the greatest deterioration
      in indexes of plasma glucose-insulin homeostasis. On the other hand, when two
      subgroups with similar mean increases in visceral AT but with different changes
      in body fat mass were compared, both subgroups showed similar changes in plasma
      glucose and insulin concentrations. CONCLUSIONS: Results of this 7-year follow-up
      study in women suggest that changes in indexes of plasma glucose-insulin
      homeostasis are significantly associated with changes in visceral AT, even after
      control for changes in body fat mass.

PMID- 8875094
TI  - Drug use in patients with diabetes.
AB  - OBJECTIVE: To describe the use of pharmaceutical medications by patients with
      diabetes in Sweden. RESEARCH DESIGN AND METHODS: We analyzed the computerized
      Surveys of Living Conditions (SLC), performed regularly in Sweden, for the years
      1988 and 1989, among individuals aged 16-84 years. Drug use (during a 2-week
      period) and the use of health services (during a 3-month period) were registered
      for subjects with diabetes (n = 361) and compared with age- and gender
      standardized figures (using the diabetes group as the standard) in subjects with
      hypertension but without diabetes (n = 980), in subjects with a musculoskeletal
      condition but without diabetes (n = 2,187), in healthy subjects free from any
      medical condition (n = 6,664), and in the general population sample (n = 12,717).
      RESULTS: The reported use of medication was higher for subjects with diabetes
      compared with the general population regarding overall use (92.5 vs. 71.9%; P <
      0.001), the use of cardiovascular drugs (52.2 vs. 36.3%; P < 0.001), all use of
      analgesics (43.8 vs. 36.5%; P < 0.05), and use of psychoactive drugs (23.5 vs.
      15.3%; P < 0.01). Compared with the hypertension group, the use was lower
      regarding cardiovascular drugs (52.2 vs. 93.3%; P < 0.001), and compared with the
      musculoskeletal group, the use was lower regarding all use of analgesics (43.8
      vs. 56.5%; P < 0.01) and the use of herbal products (6.8 vs. 11.8%; P < 0.05),
      but was higher regarding cardiovascular drugs (52.2 vs. 37.8%; P < 0.001). The
      use was higher compared with the healthy individuals, regarding all groups of
      drugs with the exception of vitamins and herbal products. CONCLUSIONS: Diabetic
      subjects have a higher overall use of drugs compared with the general population.
      Compared with other chronic illnesses, the differences are small except for
      disease-specific drugs (cardiovascular drugs in the hypertension group and
      analgesics in the musculoskeletal group). The main difference concerns the
      comparison with healthy subjects who had a markedly higher drug rate among
      diabetic subjects, thus signifying a greater impact on health.

PMID- 8875095
TI  - Erythrocyte sodium-hydrogen exchange and microalbuminuria in type I diabetes.
AB  - OBJECTIVE: To evaluate the relationship between sodium-hydrogen (Na+/H+) exchange
      and microalbuminuria (an abnormal urinary albumin/creatinine ratio in morning
      collections) in IDDM patients. RESEARCH DESIGN AND METHODS: Amiloride-sensitive
      H+ efflux from cells acid loaded at pH 6.5 (defined as erythrocyte Na+/H+
      exchange) was measured in normotensive IDDM patients with microalbuminuria and
      normal renal function (n = 16, serum creatinine < 106.1 mumol/l) and compared
      with both matched uncomplicated normoalbuminuric diabetic subjects and normal
      subjects (n = 16 each). RESULTS: Erythrocyte Na+/H+ exchange was elevated to a
      similar extent in diabetic patients with and without microalbuminuria. Blood
      pressure and lipids were normal in both diabetic groups. Daily insulin
      requirement, blood glucose, and glycated hemoglobin were higher and retinopathy
      more frequent in microalbuminuric patients. CONCLUSIONS: The abnormal erythrocyte
      Na+/H+ exchange of type I diabetic patients was unrelated to microalbuminuria and
      could not be ascribed to hypertension or dyslipidemia. Furthermore, the degree of
      metabolic control seemed to influence the progression of diabetic nephropathy,
      but not the abnormal antiport activity. The data imply that Na+/H+ exchange is an
      unlikely marker of nephropathy in type I diabetic patients.

PMID- 8875096
TI  - High prevalence of hepatitis C virus infection in diabetic patients.
AB  - OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in
      diabetic patients and to investigate the influence of several epidemiological and
      clinical factors on HCV infection. RESEARCH DESIGN AND METHODS: A total of 176
      consecutive diabetic patients were compared with 6,172 blood donors, matched by
      recognized risk factors to acquire HCV infection. Serologic testing for anti-HCV
      was done using a second-generation commercial enzyme-linked immunosorbent assay
      (ELISA) and an immunoblot assay was performed in anti-HCV positive samples to
      confirm HCV specificity. Diabetic patients were divided in two groups according
      to their HCV antibody status and analyzed for the following variables: age, sex,
      type of diabetes, duration of disease, mode of therapy, late diabetic
      complications, previous blood transfusions, intravenous drug addiction, hospital
      admissions, major surgical procedures, and liver function tests (LFTs). RESULTS:
      A higher prevalence of HCV infection was observed in diabetic patients in
      comparison with blood donors (11.5 vs. 2.5%; P < 0.001; odds ratio 4.39; 95%
      Cl2.61-7.24). We did not detect any particular epidemiological factor for HCV
      infection in anti-HCV positive diabetic patients. In these patients, abnormal
      LFTs were observed in 72.3%, compared with only 24.7% of anti-HCV negative
      diabetic patients (P < 0.001). CONCLUSIONS: A high prevalence of HCV infection
      was detected in diabetic patients, and most of anti-HCV positive patients
      presented with abnormal LFTs. Therefore, testing for HCV infection of diabetic
      patients with an abnormal LFT is mandatory. The lack of any particular
      epidemiological factor for HCV infection in our diabetic population suggests that
      HCV may have a direct role in the development of diabetes.

PMID- 8875097
TI  - Cortical blindness and cerebral infarction associated with severe hypoglycemia.
AB  - OBJECTIVE: To describe a case of cortical blindness and cerebral infarction
      associated with severe hypoglycemia. CONCLUSIONS: The possible pathogenesis of
      the neurological defects is discussed.

PMID- 8875098
TI  - Glycemic effect of a single high oral dose of the novel sweetener sucralose in
      patients with diabetes.
AB  - OBJECTIVE: To examine the effect of a single high oral dose of the novel
      noncaloric sweetener sucralose on short-term glucose homeostasis in patients with
      IDDM or NIDDM. RESEARCH DESIGN AND METHODS: A total of 13 IDDM and 13 NIDDM
      patients with glycosylated hemoglobin levels < 10% completed this double-blind
      cross-over study. After an overnight fast, patients were administered opaque
      capsules containing either 1,000 mg sucralose or cellulose placebo, followed by a
      standardized 360-kcal liquid breakfast. Plasma glucose and serum C-peptide levels
      were measured over the next 4 h. RESULTS: Regardless of the type of diabetes,
      areas under the curves for changes of plasma glucose and serum C-peptide levels
      after sucralose administration were not significantly different from those after
      placebo. During test meals with sucralose, one episode of symptomatic
      hypoglycemia occurred in each of three IDDM patients, but these episodes were not
      considered the result of sucralose administration. CONCLUSIONS: The present
      results support the conclusion that sucralose consumption does not adversely
      affect short-term blood glucose control in patients with diabetes.

PMID- 8875099
TI  - Incidence of lower limb amputations and diabetes.
AB  - OBJECTIVE: We collected data on the incidence rates of amputations and their
      relative risk in diabetic subjects compared with the nondiabetic population.
      RESEARCH DESIGN AND METHODS: From all three hospitals in a city of approximately
      160,000 inhabitants, we obtained complete lists of nontraumatic lower limb
      amputations. From each patient record, diabetic status was determined. We
      estimated age-specific and standardized incidence rates of amputations in the
      diabetic and nondiabetic populations and in the entire population, as well as the
      relative and attributable risks due to diabetes. RESULTS: Nontraumatic lower limb
      amputations were performed on 106 residents of Leverkusen (Germany) in 1990 and
      1991. Of them, 82 (77.4%) had diabetes. Mean age was 72.0 years. In the case of
      multiple amputations, only the highest level was counted for the analysis. The
      following results were standardized to the German population. Incidence rates
      (100,000(-1) year-1) were determined to be as follows: for all amputations per
      total population, 33.8; for amputations in diabetic individuals per diabetic
      population, 209.2; for amputations in nondiabetic individuals per nondiabetic
      population, 9.4. Relative risk was 22.2; attributable risk among exposed, 0.96;
      population attributable risk, 0.72. When the study is repeated to monitor the St.
      Vincent targets (50% reduction), a reduction in the amputation rate in the
      diabetic population by 46% will be detected with 90% power. CONCLUSIONS: We found
      incidence rates similar to those in the non-Indian population of the U.S. Great
      relative and population-attributable risks indicate that improving foot care in
      diabetic individuals appears to be the main target for the reduction of
      amputations in the general population.

PMID- 8875100
TI  - Torsade de pointes in NIDDM with long QT intervals.

PMID- 8875102
TI  - Report of the International Workshop on types of Diabetes Peculiar to the
      Tropics.

PMID- 8875101
TI  - Eikenella corrodens infections. Case report in two adolescent females with IDDM.
AB  - OBJECTIVE: To alert physicians caring for patients with diabetes to the
      microorganism Eikenella corrodens and to discuss the appropriate preventive and
      therapeutic measures to take against this potentially morbid opportunistic Gram
      negative bacilli. CASES: We present two cases of extra-oral E. corrodens
      infections in adolescent females with IDDM. The first patient had diabetes of 4
      years' duration, which was moderately well controlled. Chronic finger biting
      resulted in a complex felon that evolved gradually and worsened while the patient
      received cephalexin orally. Delay in seeking further intervention resulted in
      necrosis of her distal fingertip and nail bed. The second patient had poorly
      controlled diabetes for 5 years. She developed an acute thigh abscess at an
      insulin injection site that resolved after drainage and intravenous antibiotics.
      CONCLUSIONS: E. corrodens commonly inhabits the human oral cavity and becomes a
      pathogen mostly when host defenses are impaired, causing abscesses and infections
      that are at times fatal. Patients with IDDM are compromised hosts and with daily
      microtrauma to their skin via glucose monitoring and insulin injections, are
      prone to develop E. corrodens infections that can be introduced through oral
      secretions by licking or biting their skin. Educational efforts aimed at
      preventing exposure of traumatized skin to oral secretions can minimize the risk
      of E. corrodens infections in compromised hosts. Early intravenous administration
      of antibiotics, bearing in mind E. corrodens resistance to clindamycin,
      metronidazole, and other antibiotics, coupled with prompt surgical intervention,
      is essential in successfully managing E. corrodens infections.

PMID- 8875103
TI  - Commentary: time to rethink malnutrition and diabetes in the tropics.

PMID- 8875104
TI  - Role of glucose effectiveness in the determination of glucose tolerance.

PMID- 8875105
TI  - GAD antibodies seldom disappear in slowly progressive IDDM.

PMID- 8875106
TI  - Evaluation of the performance of blood glucose meters in pregnant women.

PMID- 8875107
TI  - Ileus: a rare side effect of acarbose.

PMID- 8875108
TI  - Measurement of central adiposity. A bet each way?

PMID- 8875109
TI  - Genetic variation in the beta 3-adrenergic receptor in Japanese NIDDM patients.

PMID- 8875110
TI  - Absence of seasonal variation in the occurrence of IDDM. A study from southern
      India.

PMID- 8875111
TI  - Lipoprotein(a), apolipoprotein(a) phenotypes, and nephropathy in NIDDM patients.

PMID- 8875112
TI  - Conference report: renal disease, metformin, and the adipocyte.

PMID- 8875113
TI  - Sequencing and detection of polymorphisms in the 5' end of the human endogenous
      retroviral element, HRES-1.
AB  - Fragments of the 5' long terminal repeat (LTR) of the human endogenous retroviral
      element, HRES-1, were amplified. Single strand conformation analysis of these
      fragments in combination with sequencing revealed two polymorphic nucleotides,
      namely a HindIII and an Eco571 polymorphic site. Moreover, a number of
      differences from the previously published HRES-1 LTR sequence were detected. The
      linkage pattern of the two polymorphisms suggested the existence of three allelic
      forms of HRES-1. The frequencies of the genotypes and alleles of HRES-1 were
      determined in 158 individuals. The detection of HRES-1 markers may be useful to
      study associations between this endogenous retrovirus and various diseases.

PMID- 8875114
TI  - Serum soluble vascular-cell adhesion molecule-1 (VCAM-1) in patients with acute
      and chronic liver diseases.
AB  - Our aim was to ascertain the degree of variation of serum soluble vascular cell
      adhesion molecule-1 (VCAM-1) concentrations according to the nature and the
      severity of an underlying liver disease. One-hundred forty sera collected from
      123 patients (83 male, 40 female) with acute hepatitis (n = 14), mild chronic
      liver disease (n = 52) or cirrhosis (n = 57) of different etiologies as well as
      from 17 healthy blood donors (8 male, 9 female) were studied. Soluble VCAM-1
      concentration was measured immunoenzymatically. One-way analysis of variance
      revealed a significant variability of the mean values of soluble VCAM-1 among
      groups (F = 80.02, p < 0.0001). All groups of patients had higher soluble VCAM-1
      than controls; moreover, patients with acute hepatitis and patients with
      cirrhosis had higher soluble VCAM-1 levels than patients with mild chronic liver
      disease (Bonferroni's test, p < 0.01). These results did not change after
      stratification of patients according to the etiology (viral or toxic) of liver
      disease (two-way analysis of variance: grouping factor diagnosis, F = 60.39, p <
      0.0001; grouping factor etiology, F = 1.73, p NS). Cholinesterase, total
      bilirubin, circulating thrombocytes and blood area nitrogen were the independent
      predictors of the concentration of soluble VCAM-1. In conclusion, patients with
      liver disease have high serum soluble VCAM-1, which seems to reflect more the
      severity of impairment of liver function rather than the etiologic nature of the
      disease.

PMID- 8875115
TI  - Diagnostic value of serum lactate dehydrogenase isoenzyme and amino acid patterns
      in several schistosomal and non-schistosomal disorders as compared to other
      biochemical parameters.
AB  - Serum lactate dehydrogenase (LDH) isoenzyme and amino acid (a.a) patterns were
      evaluated in comparison to several other biochemical parameters for liver and
      renal function with the objective of clarifying the differential diagnosis of
      hepatic disorders and predicting the outcome of schistosomal infection in
      Egyptian patients. Patients examined included those with complicated hepatic
      disorders and others with different stages of schistosomal infestation, hepatoma
      or bladder cancer, in addition to a normal control group. Several biochemical
      parameters appeared to be useful in establishing consistent differences or
      similarities between the studied groups. Examples are; elevated serum AST/ALT
      ratio and methionine content in chronic schistosomiasis, elevated serum
      urea/creatinine ratio and leucine content in all schistosomal patients and
      extremely high levels of N-acetyl-beta-D-glucosaminidase (NAG) in the urine of
      non-schistosomal bladder cancer patients. In addition, characteristic LDH
      isoenzyme profiles distinguish between the studied groups, in particular
      separating chronic schistosomiasis from schistosomal bladder cancer and hepatoma
      from other hepatic disorders.

PMID- 8875116
TI  - Acid-stable serine proteinase inhibitors in the urine of Alzheimer disease
      subjects.
AB  - A comparative study of the levels of acid-stable proteinase inhibitors
      (kallikrein and trypsin inhibitors) in the urine of healthy and Alzheimer
      subjects, of both sexes, has been performed. A preliminary characterization of
      the purified inhibitors indicates that the urinary antitryptic activity is
      accounted for by the presence of the well known Urinary Trypsin Inhibitor (UTI)
      while an apparently new molecule appears to be responsible for the antikallikrein
      activity. The urinary levels of kallikrein inhibitors are very similar in healthy
      and sick subjects while the levels of trypsin inhibitors appear significatively
      increased in Alzheimer subjects of both sexes. The data presented here support
      the hypothesis that unpaired proteolytic processes could be involved in the
      pathogenesis of Alzheimer's disease and suggest that the levels of urinary acid
      stable inhibitors may prove to be useful markers of the disease.

PMID- 8875117
TI  - HLA-dependent TNF secretory response may provide an immunogenetic link between
      pre-eclampsia and type 1 diabetes mellitus.
AB  - Tumour necrosis factor (TNF) may be relevant to the pathogenesis of both pre
      eclampsia and type 1 diabetes, and there is evidence than human TNF alpha
      responses to stimuli are HLA-DR dependent. To test the hypothesis that pre
      eclampsia and diabetes may share a common immunogenetic susceptibility, 92 pre
      eclampsia patients were compared with 264 general population controls. The
      relative frequencies of individual HLA-DR antigens in pre-eclamptics were found
      to correlate with reported relative TNF alpha responses for those antigens.
      Moreover, putative high responder HLA-DR1, DR3 and DR4 alleles were significantly
      (p < 0.001) more frequent in pre-eclampsia patients (79%) than in controls (59%).
      This hypothesis could explain the weak association between pre-eclampsia and
      diabetes and may help resolve the apparently conflicting literature on HLA in pre
      eclampsia.

PMID- 8875118
TI  - A method for determining familial cancer risks in clinical practice.
AB  - There is interest in estimating familial cancer risks in clinical practice for
      counselling and determining patients' screening requirements. Empiric methods can
      be used to estimate an individual's risk, however, every family history is unique
      making such methods relatively non-specific. In contrast if an underlying genetic
      model can be assumed the risk of disease can be calculated for any individual
      using his or her family history. A method of estimating familial cancer risks
      based on segregation models and linkage data is presented and its implementation
      discussed.

PMID- 8875119
TI  - Dinucleotide repeat in the third intron of the FABP3/MDGI putative tumor
      suppressor gene.

PMID- 8875120
TI  - Unusual HLA typing in celiac disease.

PMID- 8875121
TI  - Conflicting findings in the association of maternal HLA-DR homozygosity and fetal
      loss.

PMID- 8875122
TI  - Eli K. Marshall, Jr. (1889-1966): from biochemistry and physiology to
      pharmacology and pharmacokinetics.

PMID- 8875123
TI  - The disposition of morphine and its 3- and 6-glucuronide metabolites in humans
      and animals, and the importance of the metabolites to the pharmacological effects
      of morphine.

PMID- 8875124
TI  - Application of metabolism and pharmacokinetic studies to the drug discovery
      process.

PMID- 8875125
TI  - Implications of the GUSTO trial for thrombolytic therapy.
AB  - This article discusses the impact of previous clinical observations on the
      development of the GUSTO-I protocol, particularly the absence of a survival
      benefit of alteplase (rt-PA) over streptokinase in the GISSI-2/International
      Study Group and ISIS-3 trials in spite of a higher efficacy for clot lysis. The
      demonstrated superiority of front-loaded alteplase in this large trial is
      translated into useful guidelines for the practising clinician. Risk-benefit
      analysis indicates that, in general, this thrombolytic regimen is most indicated
      in patients presenting with large amounts of jeopardized ischaemic myocardium in
      the absence of a particularly increased risk of haemorrhagic stroke. Finally, the
      impact of this study for future development in the field of acute coronary
      syndromes is evaluated, more specifically for the design of new trials with new
      fibrinolytic and antithrombotic agents. These include mutants of alteplase,
      staphylokinase, direct antithrombins and inhibitors of the glycoprotein IIb/IIIa
      platelet receptor.

PMID- 8875126
TI  - In vitro fertilisation. A review of drug therapy and clinical management.
AB  - Since the first in vitro fertilisation (IVF) pregnancy was delivered in 1978,
      this procedure has resulted in thousands of pregnancies and opened a vast new
      frontier of research and treatment for the infertile couple. Pregnancy rates with
      IVF improve as the number of high quality embryos available for transfer
      increases; therefore, ovarian stimulation agents to produce multiple oocysts for
      IVF are advantageous. Clomifene (clomiphene citrate), human menopausal
      gonadotrophin (hMG; menotropins), and subsequent generations of products are
      commonly used as stimulation agents. In conjunction with the stimulation agents,
      gonadotrophin-releasing hormone (GnRH) agonists and human chorionic gonadotrophin
      (hCG) serve as adjuvants for successful control of all events in the induction
      process. Clomifene, an estrogen agonists/antagonist, occupies the estrogen
      receptor for a longer period of time than estrogen (weeks versus hours). Because
      this signal is interpreted as low estrogen, GnRH is released, which produces a
      rise in circulating levels of follicle-stimulating hormone (FSH) and luteinising
      hormone (LH) and subsequent ovarian follicular development. Menotropins is
      collected by passing urine from menopausal donors over a Sepharose column,
      followed by removal of high molecular weight impurities by chromatography. The
      mixture of FSH and LH is biologically standardised. This product stimulates
      multiple ovarian follicular development. Urofollitrophin is produced using
      antibodies to hCG anchored to a separation column. LH then can be excluded from
      the eluate by binding to the hCG antibodies (LH immunoaffinity column). Highly
      purified FSH is obtained by passing menopausal urine over a column with
      monoclonal antibodies to FSH. The isolated FSH is then eluted from the column by
      a highly basic solution and crystallised. This product delivers FSH at a 90%
      purity and can be administered subcutaneously rather than intramuscularly. Dosage
      is standardised on a mg/kg basis. Recombinant human FSH is completely free of LH
      and offers the advantages of better batch consistency, greater purity, and
      absence of any human contaminants. It may be given both subcutaneously and
      intravenously. Genetically engineered FSH combines portions of the native protein
      with another protein (hCG) which enhances its potency and extends the half-life
      compared with wild-type FSH. Short, medium and ultra-long activity analogues of
      genetically engineered FSH may be used to tailor stimulation protocols in various
      clinical situations. Growth hormone is an adjuvant to ovarian stimulation which
      results in a decreased number of ampoules of menotropins being required to
      achieve ovulation in poor responders. Ovulation triggers include both hCG and
      GnRH agonists. Progesterone supplementation is generally used in the luteal phase
      of the IVF cycle and is administered by intramuscular injection or vaginal
      suppository. It appears that conscious sedation with midazolam, pethidine
      (meperidine) and fentanyl is nontoxic for oocyte recovery. If full anaesthesia is
      required for gamete intrafallopian tube transfer (GIFT) or zygote intrafallopian
      tube transfer (ZIFT), balanced anaesthesia with nitrous oxide and an opioid
      appears to be the most appealing option. Appropriate information on the clinical
      use of the drugs used in IVF greatly reduces patient stress associated with the
      complex multidrug regimens associated with the procedure.

PMID- 8875127
TI  - Aminoglycoside administration as a single daily dose. An improvement to current
      practice or a repeat of previous errors?
AB  - Despite the availability of newer and safer antibacterials, aminoglycosides
      continue to play a major role in the management of infections in hospitalised
      patients. The concept of single daily dose (SDD) regimens was introduced many
      years ago and is now receiving much attention as an alternative regimen for this
      class of drugs. To evaluate the rationale and clinical support for SDD schemes,
      we conducted a 'MEDLINE' search to locate relevant preclinical and clinical
      literature pertaining to this issue. The results of animal model and
      noncomparative clinical data tended to be variable and inconclusive. We were able
      to identify 28 prospective comparative clinical trials; however, only one was
      randomised, double-blind and of sufficient sample size to detect differences in
      efficacy between treatment arms, should any exist. Despite these flaws, our
      review suggests that SDD schemes appear to be no more efficacious and no less
      toxic, but may be less costly, than traditional multiple daily dose schemes. We
      also assessed the predicted disposition of tobramycin/gentamicin in 415 patients
      with known pharmacokinetic parameters. With doses of 7 mg/kg at intervals of
      between 24 and 60 hours (depending upon renal function), the maximum serum
      concentration at steady-state (Cmaxss) varied from 8.5 to 55.6 mg/L, while the
      Cminss was < 2.0 mg/L in the majority of patients. Mid-interval serum
      aminoglycoside concentrations were < 0.5 mg/L in up to 23% of patients,
      suggesting possible underdosage in certain patients with this scheme. More
      conclusive clinical evidence is necessary before SDD schemes should be adopted as
      standard clinical practice. Empirical weight-based dosage schemes appear to yield
      widely variable serum aminoglycoside concentrations which could be considered
      therapeutically inadequate or toxic.

PMID- 8875128
TI  - The therapeutic potential of neuropeptide Y. Analgesic, anxiolytic and
      antihypertensive.
AB  - Since its discovery in 1982, neuropeptide Y (NPY) has been shown to have numerous
      effects mediated by a growing number of NPY receptors in both the CNS and
      peripheral nervous system. Perhaps best appreciated is the role of NPY in the
      control of systemic blood pressure, together with its effects on feeding, anxiety
      and memory. However, recent evidence increasingly supports an important role for
      NPY in mediating analgesia and hyperalgesia by distinct central and peripheral
      mechanisms. In this review we concentrate on this important aspect of NPY
      pharmacology and consider mechanisms controlling the expression of NPY and its
      receptors. In addition, we also present the more recent data describing the other
      possible roles for NPY-NPY agonists and antagonists may be useful in the
      treatment of conditions as varied as anorexia, epilepsy, anxiety, depression,
      hypertension and heart failure.

PMID- 8875129
TI  - Combination antimicrobial therapy for bacterial infections. Guidelines for the
      clinician.
AB  - Therapy with antimicrobial combinations has been used as long as antimicrobials
      have been available. Combinations of antibiotics are often used to take advantage
      of different mechanisms of action and/or toxicity profiles. Well established
      indications for combination antimicrobial therapy include: (a) empirical
      treatment of life-threatening infections; (b) treatment of polymicrobial
      infections; (c) prevention of the emergence of bacterial resistance; and (d) for
      synergism. Disadvantages of combination therapy include: (a) increased expense;
      (b) increased risk of adverse effects; (c) antagonism; and (d) superinfection.
      Combination antimicrobial therapy should be considered for the treatment of
      serious Gram-negative infections caused by Enterobacter cloacae, Pseudomonas
      aeruginosa and Serratia marcescens, and certain Gram-positive infections caused
      by Enterococcus spp. and Staphylococcus spp. Selection of agents should be
      dependent upon local susceptibility patterns, clinical experience, site of
      infection, potential toxicities and cost.

PMID- 8875130
TI  - Quinupristin-dalfopristin.
AB  - Quinupristin-dalfopristin (RP 59500) is an injectable streptogramin antibiotic.
      It possesses a wide spectrum of activity against Gram-positive bacteria including
      methicillin-resistant staphylococci, glycopeptide-resistant. Enterococcus faecium
      and penicillin-resistant pneumococci. Quinupristin-dalfopristin has activity
      against some anaerobes and selected Gram-negative pathogens. Quinupristin
      dalfopristin, by way synergism of between its 2 components, is unaffected by most
      forms of bacterial resistance. Rare forms of macrolide-lincosamide-streptogramin
      group B resistance may affect its activity; however, at present the incidence of
      strains with this type of resistance remains low. Quinupristin-dalfopristin is
      bactericidal against streptococci and staphylococci but has weak or no
      bactericidal activity against enterococci. In a compassionate use programme, 67%
      of 95 evaluable patients with vancomycin-resistant Gram-positive infections or
      intolerant of vancomycin showed improvement with eradication of infection.

PMID- 8875131
TI  - Remifentanil.
AB  - Remifentanil is a new selective mu opioid receptor agonist of higher potency than
      alfentanil, with pharmacological effects that essentially parallel those of
      alfentanil and other opioids in this class. Unlike other opioids, remifentanil is
      rapidly hydrolysed by nonspecific plasma and tissue esterases: this imparts
      brevity of action, precise and rapidly titratable effects (due to rapid onset and
      offset), non-cumulative opioid effects and rapid recovery after cessation of
      administration. The onset of action of remifentanil is similar to that of
      alfentanil, although its offset is considerably more rapid and independent of the
      duration of infusion. Remifentanil also has a sparing effect on hypnotics and
      sedatives. Its brevity of action ensures not only a rapid resolution of adverse
      effects but also a rapid offset of analgesic effect. Therefore, appropriate
      postoperative analgesia, when necessary, should be established before
      discontinuation of remifentanil infusion. The unique pharmacokinetic profile of
      remifentanil facilitates 'real time' management of intraoperative stress, as well
      as provision of optimal intraoperative analgesia without compromising recovery
      for a variety of surgical procedures.

PMID- 8875132
TI  - Ropivacaine. A review of its pharmacology and therapeutic use in regional
      anaesthesia.
AB  - The enantiomerically pure (S-enantiomer) amide local anaesthetic drug ropivacaine
      blocked nerve fibres responsible for transmission of pain (A delta and C fibres)
      more completely than those that control motor function (A beta fibres) in in
      vitro studies. The drug shares the biphasic vascular effects common to the amide
      local anaesthetic drug class. In vitro studies indicate that ropivacaine is less
      cardiotoxic than equimolar concentrations of bupivacaine. Apart from one trial in
      women undergoing hysterectomy, clinical studies that compared the efficacy of
      different doses of epidurally administered ropivacaine in patients undergoing
      various surgical procedures did not reveal any consistent dose-related
      differences with respect to sensory blockade. However, motor blockade did become
      more intense as the dose of ropivacaine increased. Overall, direct comparisons
      show that epidural ropivacaine is less potent than epidural bupivacaine when the
      2 drugs are administered at the same concentration. However, this difference is
      less marked in terms of sensory blockade than motor blockade. The greater degree
      of separation between motor and sensory blockade seen with ropivacaine relative
      to bupivacaine is more apparent at the lower end of the dosage scale.
      Nevertheless, higher doses of ropivacaine than bupivacaine are generally required
      to elicit equivalent anaesthetic effects. Ropivacaine has been shown to induce
      successful brachial plexus anaesthesia when given at a concentration of 5 mg/ml,
      but not 2.5 mg/ml, and was as effective as bupivacaine in comparative studies in
      this indication. Limited data indicate that continuous epidural infusion of
      ropivacaine postoperatively reduces postsurgical pain in a dose-related manner.
      Morphine consumption was also reduced. Higher doses of ropivacaine were
      significantly more effective than placebo. Similarly, ropivacaine controlled
      postsurgical pain when infiltrated directly into surgical wound sites (i.e. would
      infiltration) and was as effective as bupivacaine, and more effective than
      placebo, in this regard. Adverse events associated with epidurally administered
      ropivacaine include hypotension, nausea, bradycardia, transient paraesthesia,
      back pain, urinary retention and fever. The drug appears to have an adverse event
      profile similar to that of bupivacaine. In animal studies, overdoses of
      ropivacaine were better tolerated than overdoses of bupivacaine but not lidocaine
      (lignocaine). Human volunteers tolerated a higher intravenous dosage of
      ropivacaine than bupivacaine before developing initial signs of toxicity. Thus,
      ropivacaine, according to animal data, is less cardiotoxic than bupivacaine.
      Based on available clinical data, ropivacaine appears to be as effective and well
      tolerated as bupivacaine when equianalgesic doses are compared. The greater
      degree of separation between motor and sensory blockade seen withropivacaine
      relative to bupivacaine at lower concentrations (approximately 5 mg/ml) will be
      advantageous in certain applications.

PMID- 8875133
TI  - Moclobemide. An update of its pharmacological properties and therapeutic use.
AB  - Unlike older monoamine oxidase inhibitors, which irreversibly and nonselectively
      bind monoamine oxidase (MAO), moclobemide is a reversible and selective inhibitor
      of the MAO-A isozyme. Moclobemide only weakly potentiates the pressor response
      induced by tyramine or other indirectly acting sympathomimetics; therefore, there
      is no need to avoid dietary tyramine or over-the-counter decongestants with
      moclobemide as there is with older MAO inhibitors. Recent clinical trials and
      meta-analyses have confirmed the efficacy of moclobemide in the treatment of
      depressive disorders. Moclobemide has been shown to have similar efficacy to
      tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs)
      and nonselective, irreversible MAO inhibitors. Long term follow-up studies of 6
      to 12 months' duration have demonstrated that the antidepressant efficacy of
      moclobemide is maintained. Moclobemide, given alone or in combination with
      another antidepressant, has shown some efficacy in patients with refractory
      depression; however, comparative trials are required to confirm these findings.
      Data are also available to show clinical efficacy of moclobemide in the
      management of social phobia. Comparative studies have established that
      moclobemide is better tolerated at therapeutic dosages and has less toxicity in
      overdose than TCAs and nonselective, irreversible MAO inhibitors. Moclobemide
      lacks the anticholinergic, sedative and cardiovascular effects associated with
      many of the older antidepressants. Compared with SSRIs, moclobemide has a similar
      overall tolerability, although it tends to cause fewer gastrointestinal effects
      than the SSRIs and has not been reported to interfere with sexual function. In
      summary, recent data which confirm and extend its comparative therapeutic
      efficacy and low potential for adverse effects have established moclobemide as an
      effective treatment in depressive disorders. The drug is also effective in
      patients with a primary diagnosis of social phobia. Its lack of adverse
      anticholinergic, cardiovascular, cognitive and psychomotor effects makes
      moclobemide a particularly useful option in the elderly or patients with cardiac
      disease.

PMID- 8875134
TI  - Relief of pain from osseous metastatic lesions.

PMID- 8875135
TI  - Androgen receptor phosphorylation.
AB  - Phosphorylation of transcription factors plays an important role in regulation of
      gene expression. DNA-binding, transactivation activity, and subcellular
      trafficking of specific transcription factors have been shown to be regulated by
      phosphorylation/dephosphorylation. Steroid hormone receptors are phospho
      proteins, and mutations in phosphorylation sites significantly affect the
      transactivation capacity of these ligand-dependent transcription factors. At
      present, it is unknown which amino acid residues of the human androgen receptor
      are phosphorylated and whether phosphorylation of particular sites is a
      prerequisite for proper androgen receptor function. The aim of our future
      research is to map all phosphorylation sites in the human androgen receptor, and
      to analyze their importance by mutational analysis in vitro and in vivo using a
      number of functional assays.

PMID- 8875136
TI  - Down-regulation of the mineralocorticoid receptor by dexamethasone in an
      amphibian kidney cell line (A6).
AB  - The A6 cell line, derived from Xenopus kidney, is an in vitro model of cortico
      steroid mediated transepitheial Na+ transport stimulation. We report the apparent
      down-regulation of mineralocorticoid receptor levels in A6 cells, in response to
      the presence of the synthetic glucorticoid dexamethasone in the culture medium.
      Mineralocorticoid receptor binding was suppressed to approximately 25% of control
      following 24-hour exposure to 10nM dexamethasone. Scatchard analysis of
      concentration-binding experiments show down-regulation of maximum binding
      capacity by Dex exposure with no alteration of MR affinity, i.e., alteration of
      MR number only. The effect is dose-responsive with half-maximal down regulation
      at 1nM. Maximal inhibition of binding occurred after 24-hours exposure to
      dexamethasone. The inhibitory effect of dexamethasone on MR binding was unique
      for the glucocorticoid, with no effect exhibited following similar treatment with
      an androgen, an estrogen, or a mineralocorticoid.

PMID- 8875137
TI  - Triiodothyronine-induced hyperthyroidism and reproduction in female rats.
AB  - The effect of L-triiodothyronine (L-T3)-induced hyperthyroidism on reproduction
      in female rats was studied. Treatment groups used were normal control, 1, 2, 4,
      8, and 16 micrograms L-T3/100 g body weight (b.w.)/day. Subcutaneous injections
      of L-T3 began the first day of estrus until day 1 or day 19 of lactation. All
      rats given 1, 2, or 4 micrograms L-T3 had regular estrous cycles and normal
      number of pregnancies. Levels of L-T3 at 8 or 16 micrograms results in abnormal
      estrous cycles. Only one pregnancy occurred in the 8 micrograms group and no rats
      became pregnant in the 16 micrograms group. While groups on 1 or 2 micrograms L
      T3 had normal parturition, groups on 4 micrograms or more showed signs of
      dystocia. Only the 1 microgram L-T3 group lactated to day 20, but at 67% of
      normal control. All levels above 1 micrograms showed loss of pups by day 2 of
      lactation due to lack of milk production, loss of maternal behavior, and
      cannibalism. Mammary gland wet and dried fat-free tissue (DFFT) weights were
      decreased in all treated groups except 1 microgram L-T3. The wet and DFFT weights
      of thyroids and uteri on days 2 or 20 of lactation were not altered by L-T3
      treatment, but levels above 1 microgram increased both wet and DFFT weights of
      adrenal glands and ovaries. The data indicate that the no observed adverse effect
      level (NOAEL) of L-T3 for female rat reproduction would be below 1 microgram/100
      g b.w./day. L-T3 treatment at 1 microgram/100 b.w./day or above is detrimental.
      These effects may be mediated through a hormonal imbalance due to the accelerated
      metabolic rate in reproductive tissues associated with hyperthyroidism.

PMID- 8875138
TI  - 24-hour secretion of growth hormone (GH), insulin-like growth factors-I and -II
      (IGF-I, -II), prolactin (PRL) and thyrotropin (TSH) in young adults of normal and
      tall stature.
AB  - Studies of the growth hormone (GH) secretory dynamics of children with normal and
      idiopathic short stature (ISS) have revealed that the regulation of the GH
      somatomedin (GHS) axis can differ significantly among normal individuals.
      Information on the GH secretion in idiopathic tall stature (ITS) is scarce. We
      previously showed that the GH response to stimulation with GH-releasing hormone
      (GHRH) in male, late adolescents and young adults with ITS is significantly
      greater than that of their sex and age-matched controls of average height. In the
      present study, we studied the 24-hour (hr) GH, insulin-like growth factor-I and 
      II (IGF-I and -II), prolactin (PRL) and thyroid-stimulating hormone (TSH)
      secretion by every 30 minutes (min) sampling in 12 young, healthy male Greek army
      recruits. Group I [n = 6, age 22 + 1.4 years (y.), mean + standard deviation
      (SD)] had a height of 198.5 + 4.2cm, at least 3 SD's above the mean of the Greek
      male population. Group II (n = 6, age 20.5 + 1.05 y.) had a height of 169.2 +
      3.4cm, within 2SD's of the normal mean. Serum IGF-I levels were determined in
      both unextracted and extracted samples. Our results indicated that the number of
      secretory bursts and the circadian panel of GH, IGF-I and -II, PRL and TSH were
      similar in the two groups. Both the amplitude of the secretory GH peaks (5.08 +
      3.07 vs. 3.3 + 0.8 ng/ml, p = 0.19,) and the area under the curve (AUC) of the 24
      hour GH secretion (9.8 + 5.5 vs. 6.6 + 1.3 ng/ml/hr, p = 0.2) were higher in
      group I than in group II, but the difference was not significant. A significant
      nocturnal increase of both IGF-I and -II levels was found only in extracted human
      plasma (p < 0.001), whereas measurements of IGF-I in unextracted samples failed
      to reveal circadian variation (p < 0.1). We conclude that no significant
      differences were found in this pilot study of the neurosecretory regulation of
      the GHS axis between individuals of tall and normal stature. A tendency for
      greater amount of GH secretion per secretory peak was found in persons with tall
      stature; however, this finding needs to be confirmed in a larger study. IGF-I and
      -II levels had a significant circadian variation with a large nocturnal surge,
      when measured in extracted plasma. The latter, might be explained by circadian
      variation of the circulating IGF-binding proteins and its detection appears to be
      method of extraction-dependent.

PMID- 8875139
TI  - TGF-beta 1 inhibits the cell proliferation stimulated by IGF-I by blocking the
      tyrosine phosphorylation of 175kDa substrate.
AB  - TGF-beta strongly inhibits the mitogenic effect of growth factors such as insulin
      like growth-I (IGF-I) on thyroid follicular cells. To study the mechanism of this
      inhibiting action, the effect of TGF-beta 1 on tyrosine phosphorylation of 175kDa
      substrate induced by IGF-I was investigated in FRTL-5 thyroid epithelial cells.
      After treatment with TGF-beta 1, tyrosine phosphorylation of 175kDa protein
      induced by IGF-I was inhibited in parallel with the degree of the inhibition of
      cell proliferation. However, TGF-beta 1 had no effect on tyrosine phosphorylation
      of 120kDa substrate. These results suggest that TGF-beta 1 blocks the mitogenic
      signal of IGF-I by inhibiting the tyrosine phosphorylation of 175kDa substrate in
      FRTL-5 cells.

PMID- 8875140
TI  - Acute effects of exercise at low altitude (350 meters below sea level) on
      hormones of the anterior pituitary & cortisol in athletes.
AB  - The purpose of this study was to examine the effects of exercise on anterior
      pituitary hormones (adrenocorticotropic hormone (ACTH), leutinizing hormone (LH)
      and growth hormone) as well as on cortisol at low altitude (350 meters below the
      sea level) and to compare these effects with those at a moderate level altitude
      (620 meters above the sea level). Ten male athletes with running experience
      participated in a 21-Km competitive race. Serum levels of ACTH, LH, growth
      hormone and cortisol were measured before and after the race at each of the
      altitudes. A significant increase in the serum levels of ACTH and growth hormone
      were observed in response to this exercise at low altitude. Similar exercise at
      620 meters above the sea level resulted in a significant increase only in the
      serum levels of growth hormone. Serum levels of LH were not affected by this kind
      of exercise at both altitudes. Serum cortisol levels were increased following
      exercise at both altitudes. Altogether, these observations show a differential
      response of the anterior pituitary to exercise at low and normal altitudes. These
      data suggest that ACTH may have a role in the acclimatization to exercise at low
      altitudes. The role of growth hormone and LH in this conditioning process seems
      to be insignificant. The changes in serum cortisol levels in response to exercise
      at both altitudes correlate well with the effect of exercise on energy
      metabolism.

PMID- 8875141
TI  - Effects of short-term treatment of a gonadotropin-releasing hormone agonist on
      the follicular development and gonadotropin secretion in the rat.
AB  - The gonadotropin-releasing hormone (GnRH) controls pituitary gonadotropin
      biosynthesis and secretion and therefore it is indispensable in regulating
      reproductive function. We have studied the effects of a short term treatment (7
      days) of a GnRH-agonist (GnRH-Ag) in vivo (a) on reproductive cyclicity and
      follicular development and (b) on peripheral gonadotropin secretion of normal
      cycling rat. GnRH-Ag (0.2, 1 or 5 micrograms/day), administered continuously
      through an osmotic minipump for 7-days, had a varied effect on ovarian cyclicity
      as is evident by vaginal cytology and it also decreased ovarian weight. A dose of
      1 as well as 5 micrograms/day for 7-days of GnRH-Ag caused the complete demise of
      early and late antral follicles, whereas a dose of 0.2 microgram/day of GnRH-Ag
      for 7-days caused a significant decrease in the number of late antral follicles.
      There was a remarkable increase in the number of atretic follicles in the ovary
      of rats that were treated with 5 micrograms/day of GnRH-Ag for 7-days. Ovarian
      histology showed the predominance of corpora lutea in rats treated with 1 or 5
      micrograms/day of GnRH-Ag and the interstitial cells in general appeared
      pycnotic. GnRH-Ag treatment significantly enhanced the serum LH secretion but FSH
      secretion remained unaffected. Serum PRL concentration diminished in rats that
      were treated with the highest dose (5 micrograms/day) of GnRH-Ag. Results from
      this study clearly demonstrate that GnRH-Ag treatment interferes with normal
      cyclicity of rats and it profoundly affects the follicular development.
      Therefore, it acts as an atretognic factor in the ovary.

PMID- 8875142
TI  - The possible role of endogenous substance P in the modulation of the response of
      rat pituitary-adrenal axis to stresses.
AB  - The role played by endogenous substance P (SP) in the regulation of hypothalamo
      pituitary-adrenal (HPA) axis was investigated in the rat. Normal and ether
      stressed (2 min ether-vapor inhalation) or cold-stressed (20 min at 4 degrees C)
      animals were given a bolus subcutaneous injection of 100 nmol spantide (SPA) a
      specific antagonist of SP; their blood concentrations of ACTH, aldosterone (ALDO)
      and corticosterone (B) were measured by specific RIA, 1, 2 or 4 h after the
      injection. SPA did not evoke significant changes in the basal plasma levels of
      the three hormones. Ether and cold stresses markedly raised the blood
      concentrations of ACTH, ALDO and B, being maximal response observed after 1 or 2
      h. SPA notably enhanced the responses of the three hormones to ether stress. SPA
      magnified ALDO and B responses to cold stress, but it notably depressed ACTH one.
      In light of these findings, it may be concluded that (i) endogenous SP does not
      affect basal activity of rat HPA axis, but it exerts an inhibitory action on its
      response to the stresses, especially the ether-inhalation one: and (ii) different
      mechanisms are involved in the cold and ether stress-induced activation of the
      HPA axis.

PMID- 8875143
TI  - Estrus stage-specific proteinase in uterine fluid of the rat.
AB  - An estrus stage-specific proteinase of an estimated molecular weight of 600 kDa
      was detected in uterine luminal fluid of the rat. Estradiol administrated sc to
      adult female ovariectomized and immature rats induced its production. The 600 kDa
      protein was stable to sodium dodecyl sulfate polyacrylamide electrophoresis under
      reducing conditions, and retained its proteolytic activity. The proteolytic
      activity was not inhibited by the following proteinase inhibitors: 1,10
      phenanthroline, leupeptin, phenylmethylsulfonyl fluoride and pepstatin A. The 600
      kDa proteinase was not detected in the uterus or in the spent medium in which
      uteri obtained from estrus stage of normal cycling rats or from estradiol-treated
      adult ovariectomized rats were cultured. Its presence in the uterine fluid
      suggests possible involvement in the fertilization process, viability of zygotes
      and/or implantation of blastocysts.

PMID- 8875144
TI  - Practicing safe modeling: GLP for biologically based mechanistic models.

PMID- 8875145
TI  - Estrogenicity of resin-based composites and sealants in dentistry.

PMID- 8875146
TI  - MTBE toxicity.

PMID- 8875147
TI  - Reactivity parameters in structure-activity relationship-based risk assessment of
      chemicals.
AB  - New approaches to the risk assessment process are needed that might be more
      definitive and satisfying to the scientific community, interest groups, and the
      public at large. This commentary examines an alternative approach that is based
      on understanding the relationships of chemical structure and reactivity
      properties to the toxicokinetic behavior of chemicals in biological systems. This
      approach is based on the likelihood that there is a limited number of triggering
      (reactivity) mechanisms by which chemicals can express their toxicity at the
      molecular level. The fundamental importance of electrophilic character of
      chemicals as a determinant of their critical molecular reactivities and
      interactions with biological material in the expression of toxicity is supported.
      Such an approach also takes advantage of the maturing field of
      theoretical/computational chemistry in understanding important molecular
      recognition and reactivity processes (both qualitatively and quantitatively) for
      chemicals that can underlie their biological/toxicological activity. A process
      that permits assessment of reaction equivalents delivered to biological systems
      may hold promise for grouping chemicals by common triggering mechanisms with
      clearly delineated toxicological endpoints.

PMID- 8875148
TI  - FHIT gene and cancer.

PMID- 8875149
TI  - New Persian Gulf possibilities.

PMID- 8875150
TI  - Deep sea microbes and DNA cloning.

PMID- 8875151
TI  - Free radicals and breast cancer.

PMID- 8875152
TI  - Environmental toxins and the brain.

PMID- 8875153
TI  - BRC criteria revised.

PMID- 8875154
TI  - Measuring mercury.

PMID- 8875155
TI  - The issue of amalgams.

PMID- 8875156
TI  - 2005: an EPA odyssey.

PMID- 8875157
TI  - Capturing Cryptosporidium.

PMID- 8875158
TI  - Health and respirable particulate (PM10) air pollution: a causal or statistical
      association?
AB  - Numerous studies have reported weak but statistically significant acute health
      effects of particulate air pollution. The associations are observed at levels
      below the current U.S. standard of 150 micrograms/m3 (24 hr). Health effects
      include acute increased mortality from cardiopulmonary conditions and acute
      morbidity such as hospital admissions for related diseases. We reviewed recent
      epidemiology studies to evaluate whether criteria for causality are met, and we
      conclude that they are not. The weak associations are as likely to be due to
      confounding by weather, copollutants, or exposure misclassification as by ambient
      particulate matter (PM). The results from the same metropolitan areas are
      inconsistent, and PM explains such a small amount of the variability in
      mortality/morbidity that the association has little practical significance.
      Finally, experimental chamber studies of susceptible individuals exposed to PM
      concentrations well above 150 micrograms/m3 provide no evidence to support the
      morbidity/mortality findings. None of the criteria for establishing causality of
      the PM/mortality hypothesis are clearly met at ambient concentrations common in
      many U.S. cities.

PMID- 8875159
TI  - Generation of glycolaldehyde from guinea pig airway epithelial monolayers exposed
      to nitrogen dioxide and its effects on sodium pump activity.
AB  - Pulmonary injury from nitrogen dioxide (NO2) may in part be related to the
      generation of aldehydic compounds, which bind with cellular proteins and
      subsequently impair or inhibit cell function. We examined the generation of
      aldehydes from guinea pig tracheobronchial epithelial (GPTE) cell monolayers
      exposed to NO2. With the use of dinitrophenylhydrazine (DNP) to derivatize
      aldehydic compounds, glycolaldehyde, a two carbon alpha-hydroxyaldehyde, was
      identified in elevated levels in the basolateral fluid from monolayers exposed to
      NO2. DNP-glycolaldehyde levels were 81.2 +/- 2.7 and 234.0 +/- 42.6 nM in
      response to a 1-hr exposure to 1 and 5 ppm NO2, respectively, as compared to an
      air-control value of 20.3 +/- 6.8 nM. Taking into account dilution and
      reactivity, cellular glycolaldehyde levels could have reached as high as 3 mM for
      the 60-min exposure period (i.e., 0.05 mM/min). The effects of exogenous
      glycolaldehyde on GPTE ouabain-sensitive basolateral 86Rb uptake (an index of
      Na+,K(+)-ATPase activity) were examined and compared with the actions of NO2
      exposure. Bolus addition of glycolaldehyde to the basolateral fluid at
      concentrations > or = 5 mM led to an inhibition of ouabain-sensitive 86Rb uptake,
      while lower concentrations had no effect. the effects of exogenous glycolaldehyde
      differ from NO2 exposure, which led to a sustained elevation of ouabain-sensitive
      86Rb uptake with presumed generation of glycolaldehyde at a continuous low level.
      Glycolaldehyde does not appear to play a significant role in the acute
      alterations of sodium pump activity, suggesting that the NO2-induced changes in
      Na+,K(+)-ATPase activity of GPTE monolayers probably are further mediated by
      other lipid peroxidation products/oxidation processes yet to be identified.

PMID- 8875161
TI  - Second moment method for evaluating human health risks from groundwater
      contaminated by trichloroethylene.
AB  - Pollutants in groundwater aquifers may constitute a significant human health
      risk. A large variation in response may result among human populations
      experiencing the same level and duration of exposure to pollutants. Variability
      in response, as a result of exposure to a carcinogenic contaminant such as
      trichloroethylene (TCE), can be represented by a distribution function of safe
      doses. Spatial variability in aquifer characteristics and contaminant transport
      parameters requires the use of stochastic transport models to quantify
      variability in exposure concentrations. A second moment method is used to
      evaluate the probability of exceeding safe dose levels for a contaminated
      aquifer. The name of this method stems from the fact that the formulation is
      based on the first and second moments of the random variables. With this method,
      the probability is a function of the variability of contaminant concentration
      (which incorporates variability in hydrogeologic parameters such as hydraulic
      conductivity) and the variability in response in the human population. In this
      manner, the severity of the health risk posed by a contaminated aquifer and the
      evaluation of appropriate strategies and technologies for aquifer remediation are
      a function of contaminant concentrations and human health risks. The
      applicability and limitations of this method are demonstrated with data on
      groundwater contaminated by TCE at Hill Air Force Base, Utah.

PMID- 8875160
TI  - PBPK modeling/Monte Carlo simulation of methylene chloride kinetic changes in
      mice in relation to age and acute, subchronic, and chronic inhalation exposure.
AB  - During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm; 6
      hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition
      coefficient determinations were conducted on female B6C3F1, mice after 1 day, 1
      month, 1 year, and 2 years of exposure. Using physiologically based
      pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap
      resampling for data analyses, a significant induction in the mixed function
      oxidase (MFO) rate constant (Vmaxc) was observed at the 1-day and 1-month
      exposure points when compared to concurrent control mice while decreases in
      glutathione S-transferase (GST) rate constant (Kfc) were observed in the 1-day
      and 1-month exposed mice. Within exposure groups, the apparent Vmaxc maintained
      significant increases in the 1-month and 2-year control groups. Although the same
      initial increase exists in the exposed group, the 2-year Vmaxc is significantly
      smaller than the 1-month group (p < 0.001). Within group differences in median
      Kfc values show a significant decrease in both 1-month and 2-year groups among
      control and exposed mice (p < 0.001). Although no changes in methylene chloride
      solubility as a result of prior exposure were observed in blood, muscle, liver,
      or lung, a marginal decrease in the fat:air partition coefficient was found in
      the exposed mice at p = 0.053. Age related solubility differences were found in
      muscle:air, liver:air, lung:air, and fat:air partition coefficients at p < 0.001,
      while the solubility of methylene chloride in blood was not affected by age (p =
      0.461). As a result of this study, we conclude that age and prior exposure to
      methylene chloride can produce notable changes in disposition and metabolism and
      may represent important factors in the interpretation for toxicologic data and
      its application to risk assessment.

PMID- 8875162
TI  - Monte Carlo results for the 3-poly test for animal carcinogenicity experiments.
AB  - By using a two stage model of carcinogenesis, we generated Monte Carlo studies to
      assess the efficiency and robustness of the 3-poly test for animal
      carcinogenicity experiments. The Monte Carlo results indicate that the 3-poly
      test is quite powerful for detecting the carcinogenic effects of complete
      carcinogens, moderate promoters, and initiators with moderate or large effect,
      but, in some cases, it is less powerful for weak initiators or weak promoters. As
      expected, the 3-poly test is insensitive to the toxicity of many agents.

PMID- 8875163
TI  - The three Rs: the way forward.

PMID- 8875164
TI  - Closure of muscular ventricular septal defects through a left ventriculotomy.
AB  - OBJECTIVE: To evaluate the results of closure of muscular ventricular septal
      defects through a left thoracotomy. METHODS: Records of 23 children operated
      consecutively between 1972 and 1990 were studied. Age of patients was 2.8 +/- 3
      years (2 months-10 years), weight 8.9 +/- 5.7 kg (2.6-22 kg). Ten patients (43%)
      had undergone one and 4 patients (17%) two previous cardiac operations. Late
      follow-up was obtained from direct examination of patients or from reports of
      their referring physicians. Bypass time was 89 +/- 28 min (66-167 min). The aorta
      was cross-clamped for 44 +/- 15 min (21-66 min). Until 1977 operations were
      performed with moderate hypothermia and intermittent aortic cross-clamping. After
      1978 deep hypothermia (20-25 degrees C) and cold crystalloid cardioplegia was
      used. Ventricular septal defects not accessible from other approaches were closed
      through a small fish-mouth incision in the apex of the left ventricle. Patients'
      data were sampled and stored in a computerised database. Risk factors were
      evaluated by stepwise logistic regression. RESULTS: Four patients died in the
      hospital (17%); two died later. Two required reoperation for residual/recurrent
      defects. All patients, except two from abroad, were available for follow-up,
      which ranged from 36 months to 18 years (mean 11.3 years). All were in NYHA class
      I. Only two risk factors were identified: the number of ventricular septal
      defects (P < 0.05) and associated atrial septal defect (P < 0.02). Early
      echocardiographic evaluation showed good LV size and function in all except one
      patient, who had a perioperative septal infarction. Late echocardiography
      performed in six patients demonstrated normal LV shortening without evidence of
      regional wall abnormality. CONCLUSIONS: Left ventriculotomy is a useful approach
      for closure of low muscular ventricular septal defects in selected patients.

PMID- 8875165
TI  - Relationships between the dimensions of the human aortic and pulmonary valve
      leaflets: implications on Ross' operation.
AB  - The technique of replacing the aortic valve with the patient's pulmonary valve
      and the implantation of a homograft in the pulmonary position was first
      introduced by D. Ross in 1967. Despite the many advantages and successes of this
      procedure, it frequently results in some degree of valve insufficiency. In order
      to optimize the results of Ross' operation, we carried out a comparative study (n
      = 22) of the relative dimensions of the human aortic and pulmonary valve leaflets
      using a digitizer. The digitizer supplies the spatial coordinates of a given
      point (in a pre-chosen reference frame), by the positioning of its sensor on that
      point. By digitizing relevant points marked on the arterial wall we were able to
      calculate the distance between the commissures and the perimeter of each leaflet.
      Analysing the values thus obtained, we found that in 17 of the 22 cases studied
      (77.3%) there was one orientation (out of the three anatomically possible
      orientations) of the pulmonary valve, relative to the configuration of the
      recipient aortic root, that was clearly better than the other two. This study led
      to the formulation of a "rule" that, in most of the cases studied (86.4%), led to
      the best fitting orientation of the autograft using the knowledge of the
      intercommissural distances.

PMID- 8875166
TI  - Anomalous origin of left coronary artery. Evolution of surgical treatment.
AB  - OBJECTIVE: To evaluate contemporary surgical techniques in the correction of
      anomalous origin of the left coronary artery from the pulmonary artery. METHODS:
      Eleven infants were operated upon during a ten year period by one surgeon. The
      anomalous coronary artery arose from the main pulmonary artery in ten and the
      right pulmonary artery in one patient. Direct reimplantation used in eight and
      the intra-pulmonary artery tunnel technique in three. Delayed sternal closure was
      used in the immediate post-operative period in five patients. RESULTS: There were
      no deaths within the 30 day post-operative period. At cardiac catheterisation and
      coronary angiography in seven patients, six showed normal left ventricular
      function and serial improvement of left ventricular shortening fractions.
      Pulmonary artery obstruction and aortopulmonary communications were observed in
      two patients in which the tunnel technique was used. One patient has required
      transplantation of the heart. CONCLUSION: Direct reimplantation is probably
      always possible and is the operation of choice. In the short and intermediate
      term there is improvement of left ventricular function in most patients.

PMID- 8875167
TI  - Allograft reconstruction of the right ventricular outflow tract.
AB  - OBJECTIVE: Evaluation of allograft reconstruction of the right ventricular
      outflow tract (RVOT). METHODS: From 1986 to April 1995, 201 allografts (146
      pulmonary, 55 aortic) were implanted in 189 patients for conduit reconstruction
      of the RVOT in congenital heart disease or in the pulmonary autograft procedure.
      The mean age at allograft implantation was 16 years (range 2 weeks - 54 years).
      The primary diagnoses of these patients were truncus arterious (n = 19, 10%),
      transposition of the great arteries (TGA) with ventricular septal defect (VSD)
      and pulmonary atresia (PA) or stenosis (PS) (n = 14, 7%), PA with VSD (n = 26,
      14%), PA or PS with intact septum (n = 7, 4%), tetralogy of Fallot (n = 44, 23%),
      corrected TGA with PA or PS (n = 11, 6%), tricuspid atresia (n = 9, 5%), aortic
      valve pathology for pulmonary autograft procedure (n = 55, 29%), and
      miscellaneous (n = 4, 2%). The allograft implantation was a reoperation in 54
      patients (29%). RESULTS: The mean follow-up was 2.5 years (range 4 weeks-9
      years). Six patients died in hospital (3.2%). Patient survival at 5 years was 91%
      (95% CL 86-95%). Freedom from all valve-related events (2 deaths, 17
      reoperations, one endocarditis), as determined during reoperation or autopsy at 5
      years was 78% (95% CL 65-86%). Freedom from structural allograft failure was 83%
      (2 deaths, 12 reoperations, 95% CL 70-90%). Allografts implanted for congenital
      right heart defects failed earlier than allografts used for pulmonary autograft
      procedures (P = 0.05). Aortic allografts showed structural failure more often
      than pulmonary allografts (P = 0.05). There were more valve-related events in
      patients of a younger age at implantation (P = 0.02) and in those allograft
      valves from younger donors (P = 0.004). CONCLUSIONS: Allograft RVOT
      reconstruction is an adequate surgical therapy. The allograft should preferably
      be pulmonary. A younger age at implantation is a risk factor for allograft
      failure. Donor age may be a thus-far underestimated risk factor for allograft
      degeneration.

PMID- 8875168
TI  - Gastrointestinal complications after orthotopic cardiac transplantation.
AB  - OBJECTIVE AND METHODS: A retrospective chart review was performed on all patients
      undergoing orthotopic cardiac allograft transplant at Oregon Health Sciences
      University. Our purpose was to evaluate the incidence of gastrointestinal
      complications in these patients, and to assess the effect of immunosuppression.
      RESULTS: From December, 1985, to June, 1994, 240 recipients underwent 250
      orthotopic cardiac allograft transplants at Oregon Health Sciences University
      with a 30 day mortality of 15 patients (6.3 +/- 3.0%). Of the 225 operative
      survivors, the follow-up ranges from 1.0 month to 8.8 years with a mean of 39.9
      +/- 1.9 months. In our population of late survivors, 21 recipients (9.3%) have
      had gastrointestinal complications (GIC). Hepatobiliary (29%), peptic ulcer
      (14%), and pancreatic (14%) complications were the most prevalent. Surgical
      intervention was required in 19 patients (90%). Twelve procedures (63%) were
      either emergently or urgently performed, and seven procedures (37%) carried out
      electively. Operative mortality was 33% in those patients with an emergent or
      urgent intervention. There was no operative mortality among those who had an
      elective procedure. CONCLUSION: Maintenance prednisone dose was higher in
      patients with GIC than in those patients without GIC, 16.1 +/- 2.5 mg versus 7.3
      +/- 0.2 mg (P = 0.001), respectively. However, immunosuppression therapy for
      rejection episodes (i.e., Solumedrol megapulse or OKT3 therapy) was not related
      to an increased incidence of GIC. We present a review of our 21 cardiac
      transplant recipients to emphasize the potential for severe GIC and their
      corresponding perioperative morbidity and mortality.

PMID- 8875169
TI  - Comparison of low potassium Euro-Collins solution and standard Euro-Collins
      solution in an extracorporeal rat heart-lung model.
AB  - OBJECTIVE: Euro-Collins solution (EC) is routinely used in lung transplantation.
      The high potassium of EC, however, may damage the vascular endothelium, thereby
      contributing to postischemic reperfusion injury. To assess the influence of the
      potassium concentration on lung preservation, we evaluated the effect of a "low
      potassium Euro-Collins solution" (LPEC), in which the sodium and potassium
      concentrations were reversed. METHODS: In an extracorporeal rat heart-lung model
      lungs were preserved with EC and LPEC. The heart-lung blocks (HLB) were perfused
      with Krebs-Henseleit solution containing washed bovine red blood cells and
      ventilated with room air. The lungs were perfused via the working right ventricle
      with deoxygenated perfusate. Oxygenation and pulmonary vascular resistance (PVR)
      were monitored. After baseline measurements, hearts were arrested with St.
      Thomas' solution and the lungs were perfused with EC or LPEC, or were not
      perfused (controls). The HLBs were stored for 5 min or 2 h ischemic time at 4
      degrees C. Reperfusion and ventilation was performed for 40 min. At the end of
      the trial the wet/dry ratio of the lungs was calculated and light microscopic
      assessment of the degree of edema was performed. RESULTS: After 5 min of ischemia
      oxygenation was significantly better in both preserved groups compared to the
      controls. Pulmonary vascular resistance was elevated in all three groups after 30
      min reperfusion at both ischemic times. After 2 h of ischemia PVR of the group
      preserved with LPEC was significantly lower than those of the EC and controls
      (LPEC-5 min: 184 +/- 65 dynes * sec * cm-5, EC-5 min: 275 +/- 119 dynes * sec *
      cm * cm-5, LPEC-2 h: 324 +/- 47 dynes * sec * m-5, EC-2 h: 507 +/- 83 dynes * sec
      * cm-5). Oxygenation after 2 h of ischemia and 30 min reperfusion was
      significantly better in the LPEC group compared to EC and controls (LPEC: 70 +/-
      17 mmHg, EC: 44 +/- 3 mmHg). The wet/dry ratio was significantly lower in the two
      preserved groups compared to controls (LPEC-5 min: 5.7 +/- 0.7, EC-5 min: 5.8 +/-
      1.2, controls-5 min: 7.5 +/- 1.8, LPEC-2 h: 6.7 +/- 0.4, EC: 6.9 +/- 0.4,
      controls-2 h: 7.3 +/- 0.4). CONCLUSIONS: We thus conclude that LPEC results in
      better oxygenation and lower PVR in this lung preservation model. A low potassium
      concentration in lung preservation solutions may help in reducing the incidence
      of early graft dysfunction following lung transplantation.

PMID- 8875170
TI  - Excellent outcome of cardiac transplantation using domino donor hearts.
AB  - OBJECTIVE: Domino cardiac transplantation affords flexible and optimal organ
      utilization, provides hearts unaffected by brain death, allows prospective tissue
      matching, and subsequent transplantation with short allograft ischemic times. A
      retrospective review of our experience with domino cardiac transplantation has
      been made. METHODS: Seventy-two of 119 patients who underwent heart-lung
      transplantation from 1988 on served as domino cardiac donors (40 males, 32
      females; mean age of 32 years; mean weight of 51 kg). The domino donor diagnoses
      were cystic fibrosis (n = 47), bronchiectasis (n = 9), primary pulmonary
      hypertension (n = 6), emphysema (n = 7), pulmonary fibrosis (n = 2) and
      Eisenmenger's syndrome (n = 1). Forty-seven domino hearts were transplanted at
      our institution and 25 were exported to other centres in the United Kingdom. The
      72 domino cardiac recipients were 62 males and 10 females, mean age of 47 years,
      mean weight of 60 kg, with ischemic heart disease (n = 32), cardiomyopathy (n =
      36) and other conditions (n = 4). RESULTS: There were four deaths (5.6%) at less
      than 30 days (2 from multiple organ failure, 1 from primary allograft failure and
      1 from acute rejection). Actuarial survival estimates and 1 and 5 years were 77
      +/- 5.2% nd 69 +/- 6.3%, respectively. This compared favourably with survival
      data obtained in 234 non-domino cardiac recipients. In the patients transplanted
      at Papworth, there was no difference in the incidence of rejection (0.6 +/- 0.05
      versus 0.7 +/- 0.03 events per 100 patient days for the first 12 months) or in
      the freedom from graft atherosclerosis (74 +/- 3% versus 70 +/- 3% at 5 years)
      between the domino and non-domino groups. CONCLUSIONS: The use of domino hearts
      donated by recipients of heart-lung transplants is beneficial and is associated
      with an excellent early and longer-term outcome.

PMID- 8875171
TI  - The relevance of abnormal motility patterns in intra-mural oesophageal
      leiomyomata.
AB  - OBJECTIVE: Abnormal oesophageal motility patterns of the obstructive type in
      patients with gastro-oesophageal reflux without clinical evidence of obstruction
      raise the possibility of some co-existing problem. METHODS: In order to elucidate
      the relevance of such motility we studied two patients who were diagnosed as
      manifesting gastro-oesophageal reflux without herniation on full oesophageal
      investigations including radiology, ambulatory pH metry and endoscopy. In both
      patients leiomyomata were enucleated from the gastro-oesophageal junction at the
      time of surgery for reflux and subsequent oesophageal motility studies showed a
      return to near normal patterns. We studied, in retrospect, the motility patterns
      of two other patients with dysphagia due to a leiomyoma in the middle and upper
      oesophagus, respectively, and in whom the diagnosis of an oesophageal leiomyoma
      was made on clinical and radiological criteria. One of these patients was also
      studied post-operatively. RESULTS: A detailed study of these motility patterns
      shows exaggerated oesophageal contractions without features specific to achalasia
      cardia or localised oesophageal spasm, and that these features are reversed by
      surgical enucleation of the tumour. CONCLUSIONS: In these four patients the
      abnormal motilities are attributable to the presence of the intramural tumours
      despite the absence of clinical evidence of obstruction.

PMID- 8875172
TI  - A prospective risk analysis of contemporary thoracic surgery.
AB  - OBJECTIVE: The results of surgical therapy can only be accurately judged if the
      patients' characteristics and their impact on the outcome are known. The purpose
      of this study was to identify the risk factors of contemporary thoracic surgery,
      which could serve as a basis for a risk-matched comparison of different surgical
      techniques. METHODS: The data of 15 patients' undergoing thoracic surgery were
      prospectively documented. The outcome of the various operative procedures applied
      was statistically correlated with the access procedure, sex, age, body mass,
      dignity of underlying disease and six concomitant diseases. RESULTS: Four
      patients died within 30 days of surgery (mortality: 2.6%). Morbidity comprising
      all complications (class I) and morbidity comprising only complications of
      consequence for postoperative therapy (class II) rose with the number of
      concomitant diseases (50%/0% with no concomitant disease, 89%/33% with more than
      three concomitant diseases). Univariate testing identified malignant disease (P =
      0.002), male sex (P = 0.003), body mass index of less than 20 and more than 27
      kg/m of the expected level according to the Quetelet rule (P = 0.013) and a
      combination of concomitant respiratory and cardiocirculatory disease (P = 0.022)
      as being associated with class I morbidity. Male sex was significantly coincident
      with class II morbidity (P = 0.020). Logistic regression analysis demonstrated
      that these characteristics also had independent influence on class I morbidity (P
      = 0.022, P = 0.001, P = 0.023, P = 0.028). CONCLUSION: It is concluded that these
      characteristics are important predictors of morbidity of thoracic surgery. If a
      non-randomized comparison of the outcome of thoracic operations or different
      access strategies like thoracotomy or thoracoscopy is intended, at least these
      patient features should be documented and used as a basis for matching pairs.

PMID- 8875173
TI  - Surgery for non-small cell lung cancer with unsuspected metastasis to ipsilateral
      mediastinal or subcarinal nodes (N2 disease).
AB  - OBJECTIVE: Although the results after surgery for N2 disease are disappointing,
      there seems to be a subgroup of patients which may benefit from primary
      resection. These patients have clinically unrecognized N2 involvement that is
      discovered only at the time of thoracotomy (unsuspected or unforeseen N2
      disease). It was the aim of this retrospective study to analyze the survival
      after resection for unforeseen N2 disease and to evaluate different prognostic
      factors. We were interested to see whether our strategy of rigorous staging of
      the mediastinum with mediastinoscopy or anterior mediastinotomy had an effect on
      the resectability rate and survival of unsuspected N2 disease. METHODS: Between
      1985 and 1990, 859 patients with potentially operable non-small cell lung cancer
      were referred to our surgical department. Despite rigorous preoperative staging
      with computed tomography scan and cervical mediastinoscopy and/or anterior
      mediastinotomy, 103 patients (14.5%) had unsuspected N2 disease at thoracotomy.
      The tumor could be completely resected in 90 patients (87.5%). RESULTS: The 5
      year survival after complete resection was 22%. Histology of the tumor, number of
      involved levels and extent of nodal disease had no effect on survival.
      CONCLUSION: We conclude that resection is justified in patients with unforeseen
      N2 disease. Rigorous staging of the mediastinum by cervical mediastinoscopy or
      anterior mediastinotomy results in a high resectability rate and avoids
      unnecessary thoracotomies. Mediastinoscopy plays a central role in the staging of
      patients with carcinoma of the lung.

PMID- 8875174
TI  - Surgical treatment of spontaneous pneumothorax by wedge resection without
      pleurodesis or pleurectomy.
AB  - OBJECTIVE: Evaluation of wedge resection of the lung without pleurodesis or
      pleurectomy as a method of surgical treatment for spontaneous pneumothorax in
      terms of complications, recurrence rate and postoperative complaints. METHODS:
      Retrospective study of 132 operations for spontaneous pneumothorax in 120
      patients (84 men and 36 women: mean age 34 years, range 14-77) performed between
      1974 and 1993. The mean observation time was 84 months (range 6-229) and a 100%
      follow-up rate of all survivors (97%) was achieved. RESULTS: The indications for
      surgery were recurrent pneumothorax (52%), persisting air leak during first
      episode (45%), or hemothorax (3%). Perioperative findings were single bullous
      disease (86%), 2-3 bullae (6%), diffuse bullous disease (5%) and no bullous
      disease in 3% of the cases. The overall complication rate was 16% (30-day
      mortality 1%, reoperation for postoperative bleeding 2%, bronchopneumonia 8%, new
      pneumothorax during hospital stay 5%). The late recurrence rate (operated lung)
      was 5%. All recurrences were successfully treated by drainage (n = 3),
      exsufflation (n = 1) or observation only (n = 3). Reoperation was not necessary.
      Thirty-seven percent of the patients had postoperative complaints which they
      associated with the operation. CONCLUSION: Lung resection without pleurodesis or
      pleurectomy is a simple, safe and effective method of the surgical treatment of
      spontaneous pneumothorax in terms of complications and recurrence rate in
      patients with limited bullous disease.

PMID- 8875175
TI  - Valve replacement with the ATS open pivot bileaflet prosthesis.
AB  - OBJECTIVE: We sought to evaluate the ATS open pivot bileaflet valve with respect
      to haemodynamics and thromboembolism. METHODS: We prospectively studied 200
      consecutive patients aged 13-80 years. One hundred and nineteen aortic, 103
      mitral and 11 tricuspid valves were replaced in 172 single, 23 double and 5
      triple valve procedures. Thirty-eight were re-operations and 51 underwent
      coronary bypass. Transvalvular gradients were determined by transoesophageal and
      transthoracic echocardiography. Patients were followed for 12 months to 3 years.
      RESULTS: There were four hospital (2%) and three late deaths, each non-valve
      related. Two patients were reoperated for partial valve dehiscence. One aortic
      reoperation patient suffered a potential transient thromboembolic event. One
      tricuspid prosthesis thrombosed after anticoagulation was discontinued but
      thrombolysis resolved this problem. There were no other thromboembolic events.
      Valve gradients were equivalent or better than those for other bileaflet valves.
      CONCLUSIONS: The ATS valve has excellent haemodynamic characteristics and a very
      low thromboembolic rate, probably related to the convex self-washing hinge
      mechanism. Consequently, we have reduced anticoagulant levels to INR
      (international normalised ratio) 1.5 to 2.0 for aortic valve patients in sinus
      rhythm. Early experience suggests that the ATS valve functions well in the
      tricuspid position.

PMID- 8875176
TI  - Balloon mitral commissurotomy: an intraoperative assessment.
AB  - OBJECTIVE: Advances in balloon catheter technology have revolutionized the
      management of obstructive cardiovascular diseases. For lesions like mitral
      stenosis, balloon commissurotomy has emerged as an alternative to surgical relief
      showing definite functional benefits in a few clinical trials, albeit with
      variable results. Such variability necessitated objective evaluation of the
      efficacy of balloon mitral commissurotomy. METHODS: The balloon mitral
      commissurotomy was carried out in 11 patients suffering from isolated mitral
      stenosis, under vision in a surgical setting. All patients were in NYHA class
      III/IV. Initially single balloon was used for mitral commissurotomy followed by
      double balloon, before completing the mitral valvotomy with surgical instruments
      whenever required. The commissural split was measured by firmly stretching the
      two commissures using nerve hooks and measuring the distance between the two
      hooks with the help of a caliper. Assessment of balloon dilation was made by
      calculating exact percentage of residual commissural split following balloon
      dilation as compared with completed mitral valvotomy. The exact percentage of
      commissural split was thus obtained by subtracting residual commissural split
      following balloon dilation from commissural split obtained after surgical open
      mitral valvotomy. RESULTS: Complete commissurotomy using the balloon technique
      was possible in two (18.2%) patients. In the remaining nine (81.8%) patients,
      balloon expansion provided only 50% to 80% of commissural split and required
      instrumental completion with good results. CONCLUSIONS: Balloon mitral
      commissurotomy, by virtue of its circumferential force, helps to develop a good
      cleavage and attains good hemodynamic improvement which may be life saving in
      critical mitral stenosis in selected group of patients with pliable mitral
      leaflets and minimal subvalvular pathology.

PMID- 8875177
TI  - Inter-observer reliability in the interpretation of coronary angiograms.
AB  - The interpretation of coronary angiograms is indispensable in determining
      procedure in coronary surgery. The aim of this study was to measure the overall
      reliability of a group of surgeons in the interpretation of coronary angiograms,
      surgical procedure and the evaluation of operative risk. Ten coronary angiograms
      were interpreted by eight cardiac surgeons at four different medical centers.
      Evaluation of coding discrepancies, in this case of multiple raters applying an
      ordinal-scale classification scheme (0, 1, 2) with no expert yardstick available
      for coding, was explored by a two-way random factor analysis of variance.
      Reliability was substantial for the assessment of stenosis irrespective of the
      artery (intraclass correlation coefficient (ICC) ranging from 0.92 to 1), and
      good for the distal part of the artery (ICC ranging from 0.83 to 0.86) as well as
      for the collateral provision (ICC ranging from 0.75 to 0.94). Agreement between
      surgeons was good with respect to the number of bypasses to be performed (ICC =
      0.88). The number of bypass per patient varied from 2.6 to 3.2 depending on the
      surgeon. Agreement as to whether or not to bypass was substantial for the right
      coronary artery (ICC = 0.92), good for the marginal artery (ICC = 0.87) and fair
      for the left anterior descending artery (ICC = 0.60) and the circumflex artery
      (ICC = 0.60). There was a higher rate of agreement concerning inferior wall
      motion (ICC = 0.98) than of the anterior wall motion (ICC = 0.78). Agreement was
      substantial for ejection fraction (ICC = 0.93), operative risk (ICC = 0.93) and
      the type of coronary tree (ICC = 0.85). With respect to the overall set of items,
      no one surgeon disagreed significantly with the rest of the group. Some
      disagreement regarding anatomy suitable for revascularization exists between
      surgeons. Surgical assessment of risk is similar. Cardiac surgeons quickly learn
      to assess risk in a similar manner, even though they might not always graft the
      same anatomic vessels or assess regional wall motion similarly.

PMID- 8875178
TI  - Vascular adhesion molecules and immunogenicity in blood vessels used as coronary
      artery bypass grafts.
AB  - OBJECTIVE: The performance of coronary bypass grafts can be affected by a variety
      of circulating cell types. The initial event in any biological effect of such
      cells is adherence to the vascular endothelium prior to migration into the
      perivascular space. We aimed to investigate the expression of molecules that
      regulate cell adhesion in blood vessels employed as bypass conduits. METHODS:
      Segments of human saphenous vein, internal mammary artery, gastroepiploic artery
      and inferior epigastric artery were stained using specific monoclonal antibodies
      against the endothelial workers EN-4, Pal-E, von Willebrand factor small (vWF),
      and the cell adhesion molecules platelet-endothelium cell adhesion molecule
      (PECAM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule-1 (VCAM-1), E-selectin, the leucocyte marker (CD45) and major
      histocompatibility complex (MHC) class I and II antigens, with visualisation by
      ABC immunoperoxidase method. RESULTS: All vessels had a strong expression of the
      endothelial specific antigens EN4, vWF, and PECAM as well as MHC class I.
      However, there was less expression of Pal-E, ICAM-1, E-Selectin and of the DR
      determinant of MHC class II. VCAM-1, DP and DQ determinants of MHC class II were
      expressed to a weaker extent. There were no marked differences in the expression
      of all the molecules examined between the four vessel types. CONCLUSION: Thus
      vessels used as bypass grafts are immunogenic and possess the potential to
      attract and interact with blood elements. Definition of the molecules responsible
      could offer opportunities for modulating the response to such interactions.

PMID- 8875179
TI  - Loss of endothelium-mediated vascular relaxation as a response to various
      clamping pressures.
AB  - The contraction/relaxation responses of thoracic aortal rings clamped with two
      clamping pressures to potassium chloride (KC1), noradrenaline and carbachol were
      studied using a scanning electron microscope (SEM) to ascertain endothelial
      lacerations. Clamp A had the tip pressure PA = 0.60 N/mm2 and clamp B PB = 5.16
      N/mm2. In 15 Wistar albino rats, weighing 328 +/- 19 g (mean +/- SD), the
      thoracic aorta was occluded for 15 min and then three vascular rings (2 mm wide)
      were excised. The proximal unclamped ring served as a control. The aorta diameter
      was calculated from the circumference of distal rings 1.61 +/- 0.01 mm (n = 15,
      dmin = 1.51 mm, dmax = 1.70 mm). The rings were challenged with cumulative
      additions of KC1 (10-80 mmol/l) to measure the contraction. Then cumulative
      relaxation on the administration of carbachol (0.01-100 mumol/l) as a response to
      noradrenaline precontraction (0.1 mumol/l) was determined. A significant loss (P
      < 0.05) of vascular relaxation in all clamped rings (clamped with PA and PB
      clamping pressures) was seen. No significant differences (P > 0.05) were observed
      for contraction between clamped and control rings clamped with clamp A, however
      the rings clamped with clamp B showed significantly reduction of contraction (P <
      0.05). No significant differences were seen from control rings between groups A
      and B (P > 0.05), as well as from clamped rings between groups A and B (P > 0.05)
      for both the contraction and relaxation parts of the experiments. With SEM, great
      endothelial lacerations with complete disruption of the endothelial layer in the
      rings clamped with the clamp B were seen, but no disruption in rings clamped with
      clamp A. Therefore endothelial vascular layers are much more susceptible to
      pressure injuries than was previously believed. The clamped vessel wall injuries,
      particularly in endothelial layers, depend on the momentary peak clamping
      pressure (MPCP) as well as on the lower stationary clamping pressure (SCP).

PMID- 8875180
TI  - Myocardial protection in chronic volume-overload hypertrophy of immature rat
      hearts.
AB  - OBJECTIVE: The benefit of cardioplegic cardiac arrest for protection of the
      immature myocardium is controversial. We therefore investigated the efficacy of
      (1) topical hypothermia alone (2) slow cooling by coronary perfusion hypothermia
      and (3) cardioplegic cardiac arrest plus topical cooling for protection of
      isolated immature rat hearts (age: 28 days). METHODS: The isolated perfused rat
      heart model was used. Hearts were subjected to 8 h of global ischemia at 10
      degrees C. The study was conducted after clinically relevant conditions of volume
      overload myocardial hypertrophy had been established non-invasively by lifelong
      feeding of a diet low in iron. Parameters of left ventricular function,
      endothelial function, the metabolic status and myocardial injury were measured.
      RESULTS: Topical hypothermia provided superior protection of hypertrophied hearts
      with recovery of maximum developed left ventricular pressure and rate of pressure
      rise at 41.2% +/- 22.3% and 34.5% +/- 20.7% (mean +/- standard deviation) of
      preischemic values (P < 0.05 versus slow cooling and versus cardioplegia plus
      topical hypothermia). The same pattern of recovery was observed among control
      hearts. The recovery of endothelial function following protection by topical
      hypothermia alone measured 55% +/- 41% in hypertrophied hearts and 62% +/- 37% in
      control hearts, but was not recordable in all other groups. In hypertrophied
      hearts post-ischemic myocardial high energy content was significantly improved
      with topical hypothermia alone for protection when compared to the other methods.
      Creatine kinase leakage during reperfusion did not differ significantly among the
      experimental groups. CONCLUSION: Rapid cooling by topical hypothermia along
      provides superior protection of hypertrophied- and non-hypertrophied-immature rat
      hearts to additional slow pre-arrest cooling. Use of St. Thomas' Hospital
      cardioplegic solution No.2 (STS 2) does not improve protection, and even hinders
      functional recovery in hypertrophied immature hearts. Endothelial injury caused
      by cold asanguinous perfusates, including cardioplegia, interferes with the
      recovery of vascular function, which in turn, may limit mechanical function.

PMID- 8875181
TI  - Arterial myocardial revascularization without cardiopulmonary bypass through a
      small thoracotomy.
AB  - The opportunity to obviate the risks associated with cardiopulmonary bypass (CPB)
      while maintaining the long-term survival previously demonstrated with the use of
      arterial grafts, led us to perform myocardial arterial revascularization without
      CPB, using a small left thoracotomy as the surgical approach. One patient was
      operated on with this technique grafting the left anterior descending artery with
      the left internal mammary artery and grafting sequentially the first diagonal
      branch and the first marginal branch with a T-graft of radial artery. A small
      anterolateral thoracotomy was performed and the proximal harvesting of the left
      internal mammary artery was video-assisted by thoracoscopy. No hemodynamic
      deterioration occurred during the procedure. The patient was discharged on
      postoperative day 5 and the postoperative course was uneventful.

PMID- 8875182
TI  - Severe mitral valve dysfunction due to unsuspected granulomatous myocarditis:
      successful cardiac transplantation following attempted mitral valve repair.
AB  - Granulomatous involvement of the myocardium is a rapidly fatal disease of
      uncertain aetiology rarely diagnosed premorbidly. We report a patient who
      presented with mitral valve incompetence and congestive cardiac failure who
      underwent a successful mitral valve repair but could not be weaned from
      cardiopulmonary bypass. Urgent heart transplantation was successfully performed
      and histological studies of the explanted heart revealed granulomatous
      myocarditis involving the mitral subvalvular apparatus. Endomyocardial biopsy may
      be necessary in young patients presenting with mitral valve disease of unknown
      aetiology.

PMID- 8875183
TI  - Spontaneous obliteration of a pseudo-aneurysm complicating an aortic homograft.
AB  - Pseudoaneurysm formation after aortic homograft replacement in patients with
      active endocarditis is a common observation and usually occurs at the site of a
      former abscess or paravalvular leak in case of prosthetic valve endocarditis. A
      53-year-old man with prosthetic endocarditis underwent aortic valve homograft
      replacement and developed a pseudoaneurysm at the right and noncoronary aortic
      sinus which was documented by Doppler echocardiography. Follow-up examination ten
      months after operation unexpectedly revealed a complete obliteration of the
      previously echo free space between the homograft and the native aortic root and,
      thus, spontaneous obliteration of the pseudoaneurysm.

PMID- 8875184
TI  - Evidence for a common origin of most Friedreich ataxia chromosomes in the Spanish
      population.
AB  - Haplotype analysis is a powerful approach to understand the spectrum of mutations
      accounting for a disease in a homogeneous population. We show that haplotype
      variation for 10 markers linked to the Friedreich ataxia locus (FRDA) argues in
      favor of an important mutation homogeneity in the Spanish population, and
      positions the FRDA locus in the region where it has been recently isolated. We
      also report the finding of a new single nucleotide polymorphism called FAD1. The
      new marker shows a very strong linkage disequilibrium with Friedreich ataxia (FA)
      in both the Spanish and French populations. suggesting the existence of an
      ancient and widespread FRDA mutations. Inclusion of FAD1 in the extended
      haplotype analysis has allowed to postulate that this main FRDA mutation could
      account for 50-90% of the disease chromosomes. The results indicate that FA,
      despite clinical heterogeneity, could have originated from a few initial
      mutations.

PMID- 8875185
TI  - Assignment of genes encoding GABAA receptor subunits alpha 1, alpha 6, beta 2,
      and gamma 2 to a YAC contig of 5q33.
AB  - A gene cluster consisting of the four gamma-aminobutyric acidA (GABAA) receptor
      subunit genes GABRA1, GABRA6, GABRAB2, and GABRG2 was assigned to a yeast
      artificial chromosome (YAC) contig of 5q33. Two of the 26 YACs of the contig are
      positive for all four subunit genes. The order of the GABR subunit genes with
      respect to known anonymous gene loci is cen-D5S380 - D5S403 - D5S529 - GABRB2 -
      GABRA1/A6 - GABRG2-D 5S422-tel. This novel YAC contig lies between known YAC
      contigs of 5q34/q35 and 5q31-q33.

PMID- 8875186
TI  - Relative frequency, heterogeneity and geographic clustering of PKU mutations in
      Norway.
AB  - We have analysed 236 Norwegian phenylketonuria (PKU) alleles by a combination of
      mutation scanning methods, restriction enzyme-based assays and DNA sequencing.
      Thirty-three different mutations constituted 99.6% of all mutant alleles (only 1
      allele remains unidentified), 23 of these have been identified also in other
      European countries. Twenty were predicted missense mutations, 6 splice mutations,
      4 nonsense mutations and 2 deletion mutations and 1 mutation disrupted the start
      codon. The 8 most common mutations represented 83.5% of the PKU alleles, with
      single allele frequencies ranging from 5.9 to 15.7%. Four of these mutations
      (R261Q, R408W, Y414C, and 1VS12nt1) are commonly occurring also in PKU patients
      in other European countries, while the other 4 (G46S, G272X, F299C, and R408Q)
      have higher frequencies in Norway than in any other country studied. Six
      mutations (I65T, L249F, P281L, Y356X, R158Q, and R252W) have frequencies between
      0.8% and 2.1%, and 19 mutations were encountered only once. The majority of PKU
      mutations were found on the same RFLP/VNTR haplotype backgrounds in Norway as in
      other European populations, suggesting that only a few of the mutations may
      represent recurrent mutations (< 3.4%). Among 10 mutations only reported for our
      population, we detected 2 de novo mutations (0.8%) arisen in Norway. From the
      birthplaces of the probands' grandparents, each mutation seemed to have an
      individual geographic distribution within Norway, with patterns of local mutation
      clustering. Our observations are compatible with multiple founder effects and
      genetic drift for the distribution of PKU mutations within Norway.

PMID- 8875187
TI  - Delineation of a 1-cM region on distal 5q containing the locus for corneal
      dystrophies Groenouw type I and lattice type I and exclusion of the candidate
      genes SPARC and LOX.
AB  - Granular Groenouw type I (CDGG1) and lattice type 1 (CDL1) corneal dystrophies
      are two distinct potentially blinding conditions. These two entities were
      recently mapped to a region on chromosome 5q. We have investigated 2 families of
      Swiss origin with CDGG1 and CDL1 by linkage analysis. Our data show a maximum lod
      score of 5.38 at theta = 0.00 for marker D5S393 in CDL1 and 4.17 at theta = 0.00
      for D5S658 in CDGG1. When combined, these families show a maximum low score of
      9.22 for D5S393 at theta = 0.00. This confirms previous reports. Furthermore, we
      describe a recombination centromeric to D5S399 in a member of the CDL1 family.
      Haplotype analysis in the 4 branches of the CDGG1 family demonstrated a common
      chromosomal region including D5S393 and D5S399 in all the affected members. By
      combining our data with previously reported mapping information and assuming that
      CDGG1 and CDL1 are allelic manifestations of the same gene, we can refine the
      location of the CDGG1/CDL1 gene to a 1-cM region on chromosome 5q. Using
      candidate genes in the 5q22-q32 interval, we investigated the possibility that
      mutations in the SPARC or LOX genes cause these corneal diseases. Several
      recombinations occurred between these two genes and CDGG1/CDL1 in our 2 families,
      thus excluding this hypothesis.

PMID- 8875188
TI  - Fabry disease: fourteen alpha-galactosidase A mutations in unrelated families
      from the United Kingdom and other European countries.
AB  - The nature of the molecular lesions in the alpha-galactosidase A gene causing
      Fabry disease in 12 unrelated families from the United Kingdom and 4 from other
      European countries was determined in order to provide precise heterozygote
      detection and prenatal diagnosis for these families. The entire alpha
      galactosidase A coding region and flanking intronic sequences were analyzed by
      amplification of genomic DNA and solid-phase direct sequencing or by SSCP
      analysis followed by solid-phase direct sequencing. Fourteen new mutations were
      identified including 10 missense mutations (M42V, R49S, C56Y, D92H, D93G, P205T,
      W236C, W287G, N298H, and W340R), 2 nonsense mutations (Q107X and Q119X) and 2
      small deletions (257del18 and 1087del1). Together with the previously reported
      mutations, a total of 33 lesions in the alpha-galactosidase A gene have been
      identified in unrelated British families, further documenting the molecular
      genetic heterogeneity of this disease.

PMID- 8875189
TI  - The majority of 22 Dutch high-risk breast cancer families are due to either BRCA1
      or BRCA2.
AB  - We have analyzed, by a combination of mutation and linkage analysis, the genetic
      basis of 22 breast cancer families in which at least 4 cases of either breast
      cancer diagnosed under the age of 60 or ovarian cancer had occurred. Chain
      terminating mutations in BRCA1 were evidenced in 6 families, and posterior
      probabilities of > 0.90 of being linked to BRCA1 in 3. The breast versus ovarian
      cancer ratio in these 9 families was approximately 2:1. Among the remaining 13
      families, significant linkage to markers flanking BRCA2 was established in the
      admixture test with a maximum multipoint lod score of 3.38, but there was no
      statistical evidence for genetic heterogeneity. The breast:ovarian cancer ratio
      in these families was 7:1, suggesting BRCA2 confers a much lower risk for ovarian
      cancer than does BRCA1. These results suggest that BRCA2 will explain a
      significant proportion of hereditary breast cancer in the Netherlands, and,
      together with BRCA1, account for the majority of all high-risk families.

PMID- 8875190
TI  - Prenatal prediction of spinal muscular atrophy. Experience with linkage studies
      and consequences of present SMN deletion analysis.
AB  - With the localisation of the gene for the autosomal recessive forms of proximal
      spinal muscular atrophies (SMA) to the chromosomal region 5q13 and the later
      detection of homozygous deletions of the SMN gene located in this region,
      prenatal prediction of SMA has become feasible and is widely applied now. In our
      experience with 77 prenatal predictions of SMA, follow-up of the 39 liveborn
      children from these pregnancies never led to a false-negative result. Application
      of SMN deletion analysis has consequences for prenatal prediction of SMA. When
      the index patient has a homozygously deleted exon 7 of the SMN gene, prenatal
      prediction and interpretation of results are straightforward. In families in
      which no DNA from the index patient is available, prenatal detection of a
      homozygous SMN deletion may be considered almost proof of SMA in the fetus.
      Absence of a deletion, however, will not guarantee an unaffected child. A real
      problem exists if the index patient does not show a homozygous deletion of SMN
      exon 7. In such cases with non-homozygous SMN deletions, one cannot be certain of
      5q linkage and autosomal recessive inheritance until other SMN mutations are
      detected. This is an argument to abstain from prenatal diagnosis by linkage
      analysis in these families.

PMID- 8875191
TI  - Assignment of genes coding for brown eye colour (BEY2) and brown hair colour
      (HCL3) on chromosome 15q.
AB  - Brown eye colour (BEY), or total brown iris pigmentation is one of the most
      common phenotypes of iris colour. Data of eye colour as well as hair colour were
      obtained for linkage analysis through an enquiry in our family material of 832
      families from Copenhagen area. By exclusion mapping with 80 markers in 120
      segregating families and 290 markers in 5 segregating families, we obtained some
      indication of a locus BEY2 for brown eye colour on chromosome 15. For possible
      confirmation, we selected a total of 45 families from our DNA bank segregating
      for BEY. All these were tested for chromosome 15 markers in the area between
      D15S11 and CYP19. We found a strong indication of tight linkage with the DNA
      polymorphism D15S165 (Z = 24.25; theta M = F = 0.010) and with the flanking
      markers D15S156 (Z = 14.04; theta M = F = 0.0.029) and D15S144 (Z = 12.99; theta
      M = F = 0.060). BEY2 is assigned to the region 15q11-15q21 by physically
      localized markers. A new locus for brown hair colour (HCL3) was localized by
      indication of linkage to BEY2 in our 45 families segregating for BEY (Z = 9.93;
      theta M = F = 0.10). The gene (DN10 or P) homologous to the pink-eye-dilution
      gene (p) in mice could be a candidate gene for BEY2 or for HCL3.

PMID- 8875192
TI  - A high-resolution radiation hybrid map of the region surrounding the Gorlin
      syndrome gene.
AB  - We have constructed a set of hybrid cell lines by irradiation of GM 64063 (human
      chromosome 9q only on hamster background) and fusion to hamster A23 Tk-, 109
      independent lines were tested by PCR with 24 markers from chromosome 9q. The
      marker density is highest in the 9q22.3-q31 region containing the gene for Gorlin
      syndrome, a familial predisposition to basal cell carcinoma. The resolution of
      our map in this region is significantly higher than other published maps and will
      enable accurate placing of new markers and genes within the 9q22.3-q3.1 region.
      This is important since yeast artificial chromosomes from the region are likely
      to contain deletions.

PMID- 8875193
TI  - Precursors of prostatic cancer: progression, regression and chemoprevention.

PMID- 8875194
TI  - Age and racial distribution of prostatic intraepithelial neoplasia.
AB  - AIMS: To study the prevalence, extent and evolution of high-grade prostatic
      intraepithelial neoplasia (HGPIN) in African-American and Caucasian men of a wide
      age range in order to help clarify the role this lesion may play in the racial
      differences of prostate cancer. METHODS: The lesion was documented in step
      sectioned, entirely submitted prostates of two study populations: 525 autopsied
      men who died of trauma and 1,000 patients who had retropubic radical
      prostatectomy for clinically localized carcinoma of the prostate. RESULTS: We
      found that HGPIN starts in young individuals and increases progressively with
      advancing age in both races but is more prevalent in African-Americans.
      Additionally, the more extensive form of HGPIN with multifocal or diffuse
      involvement of the gland appears at a younger age in African-Americans.
      CONCLUSIONS: Microscopic foci of HGPIN can be documented in males in the 3rd and
      4th decades with the lesion becoming more extensive in older men. The finding
      that HGPIN is both more prevalent and its more diffuse form appears earlier in
      African-Americans, indicates a potentially important role for this lesion in the
      race-related discrepancies associated with this disease.

PMID- 8875195
TI  - Progression of prostatic intraepithelial neoplasia to early invasive
      adenocarcinoma.
AB  - OBJECTIVE: High-grade prostatic intraepithelial neoplasia is the most likely
      precursor of adenocarcinoma. This report describes the diagnostic criteria for
      prostatic intraepithelial neoplasia, its clinical significance, and the evidence
      suggesting that it progresses to prostatic adenocarcinoma. METHODS: We reviewed
      the published evidence linking prostatic intraepithelial neoplasia and prostate
      cancer. RESULTS: Prostatic intraepithelial neoplasia has a high predictive value
      as a marker for adenocarcinoma, and its identification in biopsy specimens of the
      prostate warrants further search for concurrent invasive carcinoma. Most studies
      suggest that, if untreated, prostatic intraepithelial neoplasia will progress to
      early carcinoma, although only indirect evidence exists to support this
      hypothesis. Androgen deprivation therapy decreases the prevalence and extent of
      prostatic intraepithelial neoplasia, suggesting that this form of treatment may
      play a role in chemoprevention. Prostatic intraepithelial neoplasia does not
      appear to elevate serum PSA concentration. It is associated with progressive
      abnormalities of phenotype and genotype which are intermediate between normal
      prostatic epithelium and cancer, indicating impairment of cell differentiation
      and regulatory control with advancing stages of prostatic carcinogenesis.
      CONCLUSION: Virtually all data indicate that high-grade prostatic intraepithelial
      is premalignant, accounting for most if not all cases of prostate cancer.

PMID- 8875197
TI  - Molecular events in the early phases of prostate carcinogenesis.
AB  - Basal cells lining prostatic acini have unique morphologic and immunophenotypic
      characteristics. The role of these uncommitted cells in the genesis of cancer in
      the prostate is intriguing. Here, we discuss immunophenotypic and molecular
      features of basal cells of prostatic acini, and compare them with those of
      cytologically transformed cells of prostatic intraepithelial neoplasia (PIN) in
      both human tissues and animal models. Following a summary of the current concepts
      of molecular events in prostatic cancer, we will discuss the role of the ras
      dependent pathway in early prostate carcinogenesis with a special emphasis on
      mitogen-activated protein kinase phosphatase (MKP-1). We will also outline the
      importance of techniques such as differential display-polymerase chain reaction
      (ddPCR) followed by in situ hybridization in the characterization of genes which
      may have a critical role in early prostate carcinogenesis. Finally, we will
      underscore the role of animal models in understanding the early events leading to
      neoplastic transformation of prostate cells.

PMID- 8875196
TI  - Biomarker expression in prostatic intraepithelial neoplasia.
AB  - OBJECTIVE: This study was conducted to gain a better understanding of the
      underlying cellular events involved in the development of prostatic
      intraepithelial neoplasia (PIN) and to clarify the relationship of PIN to
      invasive prostatic adenocarcinoma (PCa). METHOD: This article reviews previous
      studies from our laboratory and others of biomarker expression in PIN and PCa.
      RESULTS: The development of PIN is characterized by increased expression of
      several biomarkers which may influence the proliferative potential of the
      dysplastic cells. Increased expression of the growth factor receptors P185erbB-2,
      p180erbB-3, as well as the product of the c-met proto-oncogene is frequently
      detected in the dysplastic luminal cells as well as malignant cells of the
      prostate. Likewise, the expression of the nm-23H1 gene product is strongly
      expressed in dysplastic and malignant cells. Increased proliferative potential of
      the dysplastic cells is directly reflected by increased expression of PCNA. In
      contrast to the enhanced expression of the biomarkers associated with
      proliferation, decreased expression of prostate-specific antigen (PSA), prostatic
      acid phosphatase (PAP) and Leu 7 by dysplastic luminal cells is indicative of an
      impairment of the process of cellular differentiation. Aberrant glycosylation as
      well as the inappropriate expression of glycosylated tumor antigens is
      demonstrated by enhanced binding of the lectin Ulex europaeus and increased
      expression of tumor-associated glycoprotein 72 (TAG-72) and the Lewis Y antigen
      in dysplastic and malignant cells. Finally, enhanced expression of proteolytic
      enzymes such as cathepsin D and the 72-kD form of collagenase IV by dysplastic
      cells may represent an integral event in the development of invasive PCa.
      CONCLUSION: The studies described in this review clearly demonstrate phenotype
      similarities of PIN to invasive PCa and furthermore support the concept that PIN
      represents a preinvasive lesion.

PMID- 8875198
TI  - Potential markers of aggressiveness in prostatic intraepithelial neoplasia
      detected by fluorescence in situ hybridization.
AB  - OBJECTIVE: High-grade prostatic intraepithelial neoplasia (PIN) represents the
      most likely precursor of prostatic adenocarcinoma. In this review, we discuss the
      utility of different techniques of interphase fluorescence in situ hybridization
      (FISH) in evaluating the genetic association between PIN and adenocarcinoma.
      METHODS AND RESULTS: Although the proportion of PIN and prostatic carcinoma foci
      that have chromosomal anomalies is similar, foci of carcinoma often have more
      alterations. This supports the hypothesis that PIN is a precursor of carcinoma.
      In some prostates, however, PIN foci have more alterations than matched carcinoma
      foci, suggesting that PIN foci can sometimes undergo more extensive chromosome
      evolution than carcinoma foci. Gain of chromosome 8 is the most common numerical
      alteration in prostatic carcinoma and PIN foci, and is associated with increasing
      cancer stage and grade. Thus, genes on chromosome 8 may play a role in the
      initiation and progression of prostatic carcinoma. One primary tumor focus
      usually shares chromosomal anomalies with associated lymph node metastases,
      implying that only one primary lesion acquires genetic alterations that allow it
      to escape the prostate. CONCLUSIONS: PIN and prostatic carcinoma have similar
      genetic changes. This supports the hypothesis that PIN is often a precursor of
      carcinoma. Genes on chromosome 8 may play a role in both initiation and
      progression of prostatic carcinoma.

PMID- 8875199
TI  - Neuroendocrine differentiation in the precursors of prostate cancer.
AB  - OBJECTIVES: To review neuroendocrine differentiation in the precursors of
      prostatic carcinoma (prostatic intraepithelial neoplasia). METHODS: Background
      information is given on the prostatic neuroendocrine cell and neuroendocrine
      differentiation in prostatic carcinoma. Neuroendocrine differentiation in
      prostatic intraepithelial neoplasia is reviewed. RESULTS: Neuroendocrine
      differentiation occurs in prostatic intraepithelial neoplasia and is intermediate
      in degree between normal (which has the most cells with neuroendocrine
      differentiation) and carcinoma. CONCLUSION: Neuroendocrine differentiation in the
      precursors of prostatic carcinoma may play a role in the pathogenesis of cancer
      but is speculative at this time. Methods to better assess neuroendocrine
      differentiation are needed.

PMID- 8875200
TI  - Analysis of the capillary architecture in the precursors of prostate cancer:
      recent findings and new concepts.
AB  - OBJECTIVE: To report on recent findings and new concepts in the remodeling of the
      capillary architecture in the precursors of prostate cancer. METHODS:
      Immunohistochemical methods have been adopted in prostate cancer and in its
      precursors (prostatic intra-epithelial neoplasia) to investigate capillary
      pattern changes-which were mainly analyzed as capillary frequency- and the degree
      of endothelial cell proliferation. Several features related to the capillary
      architecture have been considered. Manual, semiautomatic, and automatic (machine
      vision) types of evaluation have been used to quantify the features. RESULTS: The
      data available indicate that: (1) Going from normal prostate through prostatic
      intra-epithelial neoplasia up to invasive adenocarcinoma, an increasing
      proportion of capillaries becomes shorter, with open lumen and undulated external
      contour and with greater proliferation of the endothelial cells and greater
      expression of type IV collagenase. The highest proportion of touching capillaries
      is seen in normal prostate, while the lowest is found in invasive adenocarcinoma,
      being intermediate in prostatic intra-epithelial neoplasia. (2) When total
      androgen ablation is induced, there is no proliferation of the endothelium,
      whereas the capillaries are reduced in frequency and represented by small vessels
      lined by flat endothelial cells and with an open lumen. (3) Automation in the
      evaluation of the capillary architecture is feasible with a machine vision
      system. CONCLUSIONS: The progression in prostate carcinogenesis is associated
      with changes in the capillary architecture. There are some preliminary data
      indicating that total androgen ablation can inhibit the angiogenesis in
      precursors of prostate cancer.

PMID- 8875201
TI  - Role of the basal cells in premalignant changes of the human prostate: a stem
      cell concept for the development of prostate cancer.
AB  - OBJECTIVES: Prostatic intraepithelial neoplasias (PIN) result from abnormal
      differentiation and proliferation processes within the prostatic epithelial cell
      system. Recent data indicate that basal cells are essentially involved in normal
      and abnormal growth patterns of the human prostate. RESULTS: The basal cell layer
      represents the proliferative compartment and most probably houses the prostatic
      stem cell population. Basal cells are targets of several regulatory factors
      including estrogens, androgens, epidermal growth factor and other nonsteroidal
      growth factors. During the malignant transformation of the prostatic epithelium
      (PIN), the basal cell layer loses its proliferative function which is transferred
      to secretory luminal cell types. These proliferative abnormalities are attended
      by severe regulatory disorders of the programmed cell death within the prostatic
      epithelial cell system. The Bcl-2 oncoprotein which blocks the programmed cell
      death in the proliferative compartment (basal cell layer) in normal conditions,
      extends to the secretory luminal cell types in high-grade PIN lesions. This, in
      turn, may increase the genetic instability of the dysplastic epithelium. During
      the process of tumor invasion, the transformed cells lose their basal cell
      specific phenotype and acquire features of exocrine cell types which represent
      the major phenotype in common prostate cancer. At the point of stromal invasion,
      the transformed cells produce neoplastic basement membrane material which allows
      them to penetrate the extracellular matrix. CONCLUSION: These data provide
      theoretical bases for a stem cell concept in the development of prostate cancer
      and highlights the importance of basal cells in this multifactorial process.

PMID- 8875202
TI  - Atypical adenomatous hyperplasia of the prostate: a critical review.
AB  - AIMS: The aim of this report is to review the literature concerning atypical
      adenomatous hyperplasia (AAH) with specific regard to evidence in support of or
      refuting its role as a precursor lesion for prostatic adenocarcinoma. METHODS:
      The available literature was collected and critically reviewed. In addition,
      recently reported (abstract) but as yet unpublished data were included.
      Particular attention was focused on biological studies. RESULTS: There is
      considerable morphologic evidence suggesting that AAH is associated with low
      grade (Gleason patterns 1 and 2) adenocarcinoma arising in the transition zone.
      Only limited biologic studies have been performed. There is weak and limited data
      to indicate that AAH has a proliferation rate higher than hyperplasia but lower
      than adenocarcinoma. AAH is diploid, as are most examples of low-grade
      adenocarcinoma. A few markers (blood group antigens, peanut agglutinin) show
      similar patterns of expression in AAH and adenocarcinoma while others
      (carbohydrate D-galactose-N-acetyl-D-galactosamine) do not. Recent cytogenetic
      analyses have detected abnormalities of chromosome 8 in a very small proportion
      (4-6%) of cases of AAH studied. CONCLUSIONS: Presently, the only strong evidence
      linking AAH to adenocarcinoma is morphologic. The few biologic and
      molecular/cytogenetic studies performed have not provided convincing evidence to
      support or refute this possibility. Additional studies are required. Finally, in
      comparative studies of AAH with adenocarcinoma, the latter should include low
      grade transition zone tumors.

PMID- 8875203
TI  - Diagnostic limits in precursor lesions of prostatic cancer.
AB  - OBJECTIVE: Among prostatic lesions with atypical features, atypical adenomatous
      hyperplasia (AAH; microglandular proliferation with bland nuclei), and prostatic
      intraepithelial neoplasia (PIN; cellular atypia in preexisting large ducts and
      acini) are considered precursors of prostatic cancer, but these lesions are a
      continuum from the normal prostate to prostatic cancer. The objective of the
      paper is to bring attention to the pitfalls in the diagnosis of both lesions.
      MATERIAL AND METHODS: To describe the diagnostic limits in AAH and PIN, we used
      the literature information and our 76 cases of AAH and 169 patients with PIN at
      prostatic core biopsy. CONCLUSIONS: In the majority of cases, AAH appears in the
      transition zone and it is necessary to be very strict in the diagnosis in order
      to avoid confusion with microglandular BPH. One of the controversies is the
      biologic significance of prominent nucleoli in the AAH. Although the association
      of AAH with cancer is relatively scant, we have a higher incidence of cancer in
      cases with AAH than in classic BPH and we recommend complete study of the
      surgical specimen. Low-grade PIN does not need to be reported, but high-grade PIN
      should be and close follow-up is recommended if we find an isolated high-grade
      PIN. Because the clinical implications of high-grade PIN are so important,
      pathologists must be sure of the diagnosis avoiding interpretation in
      inflammatory areas. The high-molecular-weight cytokeratins may be useful in some
      cases, when the diagnosis of adenocarcinoma vs. high-grade PIN is seriously
      considered.

PMID- 8875204
TI  - Automated reasoning system in histopathologic diagnosis and prognosis of prostate
      cancer and its precursors.
AB  - OBJECTIVE: This article presents the rationale and options offered to diagnostic
      and prognostic decision support systems for prostate pathology by automated
      reasoning capabilities. METHODS: The symbolic information used in diagnostic
      decision-making is systematically ordered, compared, numerically assessed in its
      probability, and combined such that a conclusion can be drawn. The framework for
      the processing of such symbolic information may be an expert system, an inference
      network or a case-based reasoning system. Automated reasoning is implemented by
      the use of a rule base and information flow control modules. RESULTS: Automated
      reasoning allows decision support systems to follow highly adaptive decision
      sequences, capable of handling contradictory evidence, exceptions in diagnostic
      clue expression, and nonmonotonic decision-making. CONCLUSIONS: Automated
      reasoning capability in diagnostic and prognostic decision support systems allows
      highly flexible decision development, very close to human decision procedures.

PMID- 8875205
TI  - Knowledge-based image analysis in the precursors of prostatic adenocarcinoma.
AB  - OBJECTIVES: It is the objective of this study to present the use of knowledge
      guided procedures in quantitative image analysis and interpretation in
      histopathology. METHODS: The knowledge-guided procedures were implemented in the
      form of N-gram encoding methods for the search and detection of areas of
      atypicality or abnormality in histopathologic sections; they were implemented as
      expert system for automated scene segmentation based on an associative network
      with frames at each node. The extraction of histometric features from the basal
      cell layer of prostatic lesions is presented as an example of automated image
      interpretation. RESULTS: Rapid search algorithms for lesion detection were able
      to identify approximately 90% of areas labelled as atypical or abnormal by visual
      assessment, in lesions of colon, prostate and breast. Automated segmentation of
      very complex histopathologic imagery was possible with a success rate of
      approximately 80-90%, in sections of prostatic and colonic lesions. Histometry of
      the deterioration of the basal cell layer in prostatic lesions provided a
      monotonic trend curve suitable for the measurement of progression or regression.
      CONCLUSIONS: Knowledge-guided procedures bring external information, not offered
      by the imagery itself, to bear on image processing and image analytic methods.
      This has enabled automated analysis and interpretation of very complex imagery,
      such as from cribriform glands, resulting in quantitative diagnostic information.

PMID- 8875206
TI  - Animal models for the preneoplastic lesions of the prostate.
AB  - OBJECTIVES: Reliable and adequate animal models are required, not only for
      investigation of etiology, pathogenesis, and treatment of prostate cancer, but
      also for chemoprevention of prostatic carcinogenesis. METHODS: Animal models for
      the study of premalignant changes in the prostate are reviewed in the paper, with
      specific reference to the neonatally estrogenized mouse model. RESULTS: Neonatal
      treatment of newborn Han:NMRI mice with synthetic non-steroidal estrogen,
      diethylstilbestrol (DES; 2 micrograms/pup on days 1-3 after birth) promoted
      hyperplastic and dysplastic changes in the periurethral region of the prostate at
      the age of 9-18 months. Dietary soy partially inhibited the development of
      prostatic dysplasia in these neonatally estrogenized animals, which may be due to
      phytoestrogens contained in soy-rich food. CONCLUSION: Prostatic cancer and its
      possible precursors develop spontaneously, or can be induced by different
      chemical and hormonal manipulations in certain animal species and strains.
      Neonatal estrogenization of the mouse results in prostatic dysplasia, which can
      be partially prevented by dietary soy. There are morphological similarities
      between human prostatic intraepithelial neoplasia (PIN) and dysplastic changes in
      rodent prostates, but more data is needed before these dysplastic lesions can be
      considered equivalent to human PIN.

PMID- 8875207
TI  - Clinical prognostic criteria for later diagnosis of prostate carcinoma in
      patients with initial isolated prostatic intraepithelial neoplasia.
AB  - Prostatic intraepithelial neoplasia (PIN) is considered as a precursor of
      prostate cancer and is frequently associated with it. Diagnosis of PIN on a
      prostate needle biopsy without associated carcinoma is a difficult problem since
      high-grade PIN does not necessarily mean that prostate cancer is always present
      and low-grade PIN is associated with cancer as well. Definition of parameters
      predictive of the later finding of prostate cancer on repeat biopsy in patients
      with PIN is of evident interest and we have reviewed our experience and recent
      data from the literature on this topic. High grade is a strong predictor of later
      cancer found on repeat biopsy (50-100%) and in these patients, serum prostate
      specific antigen (PSA), digital rectal examination and transrectal ultrasound are
      predictors of later cancer found on repeat biopsy. High-grade PIN is, however,
      frequently associated with later cancer whatever PSA, even when < or = ng/ml. Low
      grade PIN seems to behave like BPH since the incidence of later cancer is
      extremely low when PSA is < 4 ng/ml and is high when PSA > 10 ng/ml. Patients
      with high-grade PIN should systematically be rebiopsied after 3-6 months to
      exclude cancer because they are likely to have undiagnosed cancer. Patients with
      low-grade PIN and low PSA seem to have a low risk of later cancer found on repeat
      biopsy. Patients with low-grade PIN and high serum PSA should have repeat
      biopsies because the incidence of subsequent cancer is high and comparable to
      high-grade PIN. Further investigations are needed to optimize the management of
      patients with low-grade PIN and intermediate PSA level.

PMID- 8875208
TI  - Follow-up of prostatic intraepithelial neoplasia.
AB  - Biopsy or fine-needle aspiration cytology are the only appropriate methods for
      detection of prostatic intraepithelial neoplasia (PIN). PIN has been suggested to
      be a principal precursor of invasive carcinoma of the prostate. Most reports on
      an association of PIN and invasive prostatic cancer have a follow-up of less than
      1 year, indicating that the successively diagnosed cancer most probably was
      present at the time of diagnosis of PIN. The natural history of PIN is unknown
      and detection of PIN should therefore not influence therapeutic decisions. If
      coexistent carcinoma is not found, close surveillance is recommended to identify
      a possible subsequent cancer at an early stage. Follow-up examinations should be
      performed at 6-month intervals for 2 years and thereafter annually.

PMID- 8875209
TI  - Influence of irradiation and androgen ablation on prostatic intraepithelial
      neoplasia.
AB  - OBJECTIVES: Although irradiation and endocrine therapy have been used in the
      treatment of prostatic carcinoma for several decades and the effects of such
      therapy on carcinoma and the normal prostate have been well described and
      although there is ample evidence linking prostatic intraepithelial neoplasia
      (PIN) to the origin of prostatic adenocarcinoma, there is little published
      information on the effect of such therapies on PIN. METHODS AND RESULTS: The
      extant literature on this subject is reviewed and analyzed. The literature on
      total androgen blockade is not extensive but adequate to draw conclusions. The
      literature on irradiation therapy is minimal and inadequate to draw definite
      conclusions. CONCLUSIONS: The available evidence indicates that the prevalence
      and extent of PIN in prostates that have been treated with endocrine therapy is
      reduced from what might otherwise be expected. Irradiation therapy may have
      little effect on the prevalence of PIN but might influence the extent of PIN.

PMID- 8875210
TI  - Androgen receptors in untreated and treated prostatic intraepithelial neoplasia.
AB  - OBJECTIVES: The effect of androgen deprivation therapy on the expression of
      androgen receptors (AR) and the proliferation-associated MIB-1 antigen in
      prostatic intraepithelial neoplasia (PIN) was investigated. METHODS:
      Immunohistochemistry was performed on tissue sections of prostatectomy specimens
      of patients with prostate cancer who either were not treated prior to surgery or
      received androgen blockade therapy for 3 months. Immunohistochemistry on slides,
      selected for the presence of PIN was performed with an AR-specific monoclonal
      antibody and MIB-1 using a microwave antigen-retrieval method. RESULTS: AR
      expression was present in a majority of cells in PIN of both untreated and
      treated prostatectomy specimens. In addition, a proportion of normal prostatic
      glandular cells retained AR expression. The basal cells in both untreated and
      treated PIN did not express AR. MIB-1-positive cells were identified in PIN of
      untreated and treated cases. CONCLUSIONS: PIN lesions that persist after 3 months
      of androgen deprivation therapy continue to express AR and may therefore retain
      the potential to expand after cessation of this therapy.

PMID- 8875211
TI  - Chemoprevention for prostatic intraepithelial neoplasia.
AB  - OBJECTIVES: To evaluate the potential application of chemoprevention strategies
      in prostatic intraepithelial neoplasia. METHODS: Review of relevant literature on
      chemoprevention with emphasis on prostate cancer and premalignant lesions.
      RESULTS: Chemoprevention represents a strategy designed to inhibit or reverse the
      process of carcinogenesis by administering one or several noncytotoxic chemical
      compounds. The epidemiology of prostate carcinoma indicates that this cancer is a
      prime candidate for a strategy aimed at prevention due to the extremely high
      prevalence rate, rising annual incidence, and long latent interval between the
      cancer-initiating events and the development of invasive disease. Chemopreventive
      agents may exert their inhibitory effects at different stages of the multistep
      carcinogenic process broadly categorized as initiation, promotion, and
      progression. The synthetic retinoids, polyamine synthesis inhibitors, and
      antiandrogens are among the compounds shown to have in vitro or in vivo
      chemopreventive effects in prostate carcinogenesis. A major limitation in the
      evaluation of such agents in a human prostate cancer is the long duration of
      clinical trials required to assess the efficacy with an endpoint of cancer
      development. Premalignant epithelial changes such as prostate intraepithelial
      neoplasia, or PIN, are highly associated with prostate cancer, and share many
      molecular features of invasive cancer. If the reversal or inhibition of
      intraepithelial neoplasia translates to a concomitant reduction in clinically
      relevant prostate cancer, then the pharmacological modulation of PIN may provide
      a rapid means to evaluate the effects and benefits of potential chemopreventive
      agents. CONCLUSION: Men with PIN may represent ideal candidates for
      chemoprevention protocols. The ideal agent and duration of therapy remains to be
      defined.

PMID- 8875212
TI  - Current experimental strategies for investigating human hematopoietic stem cell
      biology.
AB  - The currently available different experimental strategies for investigating the
      biology of the human hematopoietic stem cells are reviewed in this paper. There
      are discussed: (1) different approaches to isolate human hematopoietic stem
      cells, (2) available molecular techniques for investigating gene expression in
      isolated cells, and (3) functional tests evaluating their proliferative potential
      in in vitro cultures and in vivo in animal models. Important information
      regarding stem cell biology can be also gained from animal model involving: (1)
      overexpression of particular genes in transgenic mice or, (2) gene "knock-out"
      techniques using homologous recombination. The regulation of proliferation and
      differentiation of human hematopoietic stem cells can be also discerned after
      downregulation of expression of genes of interest in the early hematopoietic
      cells using antisense strategy.

PMID- 8875213
TI  - The influence of phosphorothioate oligodeoxynucleotides on various organs in
      vivo.
AB  - To characterize the distribution and toxicity of phosphorothioate antisense
      oligodeoxynucleotides ([S]ODNs) in vivo, the mice, previously injected with BV173
      leukemic cells (Philadelphia chromosome-positive chronic myeloid leukemia blast
      crisis), received intravenously 26-mer BCR-ABL antisense oligodeoxynucleotides (1
      mg/mouse/day) for 9 consecutive days. Our investigation revealed that [S]ODNs
      were distributed to almost all organs except the brain with the highest level in
      the liver, spleen and kidneys. They were also detected in CD10+ leukemic cells
      isolated from spleen and bone marrow. Intracellular distribution assay showed the
      presence of [S]ODNs most prominently in nuclear and cytoplasmic fractions. Our
      data demonstrated no significant toxicity of [S]ODNs except the increase in
      spleen weight.

PMID- 8875214
TI  - Thymocyte and splenocyte subpopulations in normal and leukemia-bearing mice after
      adrenalectomy.
AB  - Mice with i.p. inoculated leukemia L1210 cells had lower total number of
      thymocytes, and reduced number of CD4+8+ thymocytes, but increased CD4+8-
      subpopulation. Adrenalectomy reduced the CD4-8+ subset of thymocytes. Leukemia in
      adrenalectomized animals induced similar changes in the number of thymocyte
      subpopulations as observed in normal animals. However, a decrease in CD4+8-
      thymocytes was noted and the animals had decreased number of CD4-8- cells as
      well. Splenocytes of CD4+8- subpopulation were more numerous in adrenalectomized
      animals. Leukemia induced increase in the number of CD4+8- and CD4-8+ splenocytes
      in both normal and adrenalectomized animals.

PMID- 8875215
TI  - Formation of lamellar bone on the surface of woven bone is not prevented by BAPN.
AB  - To study the possible effect of collagen cross-link formation on the lamellar
      bone deposition, isolated mouse bone cells were transplanted in the syngeneic
      system and the formation of bone was followed in control and beta
      aminopropionitrile (BAPN) treated animals. Woven and lamellar bone were
      distinguished by shape of bone lacunae, PAS reaction and Sirius red staining of
      collagen fibers. BAPN was administered in various doses either subcutaneously or
      in drinking water. Bone formed in BAPN treated animals contained both woven and
      lamellar bone in similar proportion as in controls. Thus, cross-linking of
      collagen seems to be unnecessary for lamellar bone deposition.

PMID- 8875216
TI  - Distribution of some neuropeptides in the porcine inferior mesenteric ganglion.
AB  - The occurrence and distribution of vasoactive intestinal polypeptide, substance
      P, and bombesin/gastrin-releasing peptide in neuronal cell bodies and nerve
      fibers of the porcine inferior mesenteric ganglion were studied with the indirect
      immunohistochemical technique. Of all substances studied only vasoactive
      intestinal polypeptide was found in principal ganglionic neurons. The presence of
      nerve fibers immunoreactive to vasoactive intestinal polypeptide,
      bombesin/gastrin-releasing peptide, and substance P was also found in the
      ganglion. There were differences in the pattern of distribution and density of
      the nerve fibers immunoreactive to the particular peptides. Fibers containing
      vasoactive intestinal polypeptide and bombesin/gastrin-releasing peptide were
      numerous, while fibers containing substance P were comparatively scarce. The
      present results revealed both similarities and specific differences in the
      occurrence and localisation of various neuropeptides in the porcine inferior
      mesenteric ganglion in comparison with that of other mammalian species.

PMID- 8875217
TI  - Chromogranin A immunoreactivity in epithelial cells of the thymus.
AB  - We have examined the localisation of chromogranin A (CGA) in rat thymus using
      immunocytochemistry. In the adult female animals we found CGA-like
      immunoreactivity in the epithelial cells in the subcapsular zone, the outer part
      of medullary region and associated with Hassall bodies. In pregnant rats more
      epithelial cells were immunolabelled, suggesting an increase in CGA synthesis
      during pregnancy. Our results indicate that CGA may be colocalised with the
      thymic hormones in the epithelial cells of some regions of the thymus.

PMID- 8875218
TI  - Argyrophilic nucleolar organizer regions, bromodeoxyuridine labelling index and
      DNA ploidy in squamous cell carcinoma of the uterine cervix.
AB  - There is increasing evidence that rapidly proliferating tumours, i.e. those with
      a high bromodeoxyuridine labelling index (BrdUrdLI), could benefit from an
      accelerated course of radiotherapy. Also, DNA ploidy may be a prognostic factor
      in term of patients survival. Thus, measurements of cell kinetics and DNA ploidy
      might become part of routine characterization of tumours before treatment. It is
      supposed, that a simple and cheap argyrophilic nucleolar organizer regions
      (AgNOR) test reflects the proliferative status of the tumour and correlates with
      BrdUrdLI. The BrdUrdLI, AgNOR test and DNA ploidy were assessed in 49 squamous
      cell carcinoma (SCC) of the cervix (stage II B-III B) and 5 normal epithelium.
      The number of NORs per cell nucleus, the mean AgNOR particle area and the total
      AgNOR area per cell were evaluated. Significant differences in the proliferative
      rate were found within the examined groups of tumours assessed by the BrdUrdLI
      and AgNOR test. The mean BrdUrdLI values were significantly lower in normal than
      in carcinomatous cells, while for AgNOR values this was true for stage III B
      only. The mean number of AgNORs and total AgNOR area per cell were not
      significantly higher at stage III B than at stage II B, respectively. A high DNA
      aneuploidy was found in the examined tumours: 78% in stage II B and 77% in stage
      III B of disease. The results of proliferative markers were not significantly
      different in diploid than in aneuploid tumours. A significant correlation (p <
      0.0001) was found between the mean AgNOR values and BrdUrdLI, however the
      correlation coefficient was poor (r = 0.50). This was due to different fragments
      of the same tumours used in these tests. Therefore these techniques might be used
      as independent methods reflecting the proliferative rate of the tumour.

PMID- 8875219
TI  - Selective binding of Ca2+, Zn2+, Cu2+ and K+ by the physodes of the green alga
      Mougeotia scalaris.
AB  - Cells of the zygnematophycean green alga Mougeotia contain numerous globules with
      polyphenolic matrix, which resemble physodes. In order to analyse the capability
      of this compartment to sequester various ions, trichomes of Mougeotia scalaris
      were either fixed for X-ray microanalysis simultaneously in 2%
      glutardialdehyde/1% OsO4 in phosphate buffers of different K+/Na(+)-ratios, or
      embedded directly (fresh material) in Nanoplast resin. In addition, fixed
      material was treated with potassium antimonate and Ca2+ localization was examined
      by electron microscopic cytochemistry. A Ca(2+)-depletion upon fixation at
      different K+/Na(+)-ratios resulted in selective uptake of potassium, but not
      sodium. Consistent with earlier findings, calcium-binding by the polyphenolic
      physode matrix does not depend merely on electric charge but also on the presence
      of protonated/deprotonated phenolic groups, together with ester-linked carbonyl
      oxygen, which seem to be good candidates for a co-ordinate type of calcium
      binding. Nanoplast embedding turned out to be the most adequate and fastest
      preparation for X-ray microanalysis and, apart from retaining calcium, allowed
      the detection of zinc and copper inside the physodes.

PMID- 8875220
TI  - Gene therapy for thalassaemia.

PMID- 8875221
TI  - Recombinant adeno-associated virus (AAV-CFTR) vectors do not integrate in a site
      specific fashion in an immortalized epithelial cell line.
AB  - Adeno-associated virus-2 (AAV) can integrate in a site-specific manner to human
      chromosome 19 and is currently in phase I clinical trials for cystic fibrosis
      (CF) at Johns Hopkins Hospital. The goal of this study was to determine the fate
      of recombinant AAV containing the CFTR cDNA (AAV-CFTR) in an immortalized
      pseudotetraploid CF bronchial epithelial cell line (IB3-1) established from a
      patient with CF. Fluorescence in situ hybridization (FISH) and Southern blotting
      of DNA from IB3-1 cells infected with wild-type (wt) or recombinant AAV-CFTR were
      performed. CFRH2, an IB3-1 cell line with an estimated 15-20 integrated copies of
      CFTR cDNA, was used to test FISH sensitivity. All metaphase spreads had
      integrated copies: a single site in 36 of 56 (64.3%) and two sites within the
      same metaphase spread in 20 of 56 (35.7%). 3-CF-8, an IB3-1 cell line with
      integration of a partial CFTR cDNA (3.9 kb) was also analyzed by FISH.
      Integration was observed in 56 of 157 (35.7%) metaphase spreads examined. IB3-1
      cells infected with wild-type AAV showed integration in 51 of 86 (59%) metaphase
      spreads examined. Of 51 integrations, 48 (94%) were to chromosome 19. Examination
      of 67 metaphase chromosome spreads of IB3-1 cells infected with AAV-CFTR vector
      (Azero) identified four integrations (6%) to different chromosomes. No
      integration was to chromosome 19 which differs significantly (P < 0.0001) from
      wild-type AAV. We then analyzed the A35 cell line, a clone of Azero selected for
      stable CFTR expression. Genomic DNA from A35 cells did not show a single site of
      integration; however episomal AAV-CFTR sequences were abundant in the low
      molecular weight DNA fraction. Examination of 68 metaphase chromosome
      preparations identified eight distinct integrations, none to chromosome 19. These
      studies show that FISH is sensitive for the detection of a partial CFTR cDNA
      integration. Wild-type AAV integrates in a predominantly site-specific fashion.
      Recombinant AAV-CFTR integrates at low frequency in a nonspecific manner and
      persists in episomal form in this epithelial cell line.

PMID- 8875222
TI  - Production of increased titer retrovirus vectors from stable producer cell lines
      by superinfection and concentration.
AB  - Retrovirus vector titers could be increased by more than 50-fold after multiple
      superinfections of packaging cells with vector virus expressing a complementing
      host-range envelope glycoprotein. The high level of expression was stable for at
      least 90 passages in culture. The optimum conditions for density of cell seeding,
      length of incubation, and temporary storage of virus-containing medium was
      determined. This vector preparation was further concentrated by 20-fold or more
      in commercially available ultrafilters, which can be used with standard
      laboratory centrifuges. Ultrafilters from three different manufactures, with
      molecular weight cutoffs of 30-1000 kiloDaltons, were tested for concentrating
      ability and for toxicity of the concentrate on target cells. These methods can be
      used to produce vector virus containing retrovirus envelope proteins in
      milliliter volumes at titers in excess of 10(8) c.f.u./ml and in liter volumes at
      greater than 10(6) c.f.u./ml.

PMID- 8875223
TI  - Stromal cells maintain the radioprotective capacity of CFU-S during retroviral
      infection.
AB  - Retroviral vectors provide an efficient means to introduce genes into
      hematopoietic stem cells. In order to develop retroviral infection protocols
      which preserve the radioprotective capacity of CFU-S, we designed a clonal
      hematopoietic reconstitution assay. In this assay, single CFU-S-derived derived
      colonies from bone marrow cells of 5-FU-treated mice were tested for their
      capacity to prevent radiation-induced mortality. Three parameters which may
      modify stem cell potential were tested in infection protocols using a retroviral
      vector containing the gene for neomycin resistance: (1) the partition of stem
      cells between the adherent and nonadherent fraction; (2) the replacement of the
      packaging cell line by a "competent' stromal cell line; and (3) the effects of
      G418 selection. All CFU-S having radioprotective capacity were found in the
      adherent fraction when the packaging cell line or the stromal cell line (MS-5)
      chosen for its capacity to maintain long-term bone marrow culture were used
      during the co-culture. The neo resistance gene was transduced into CFU-S with the
      same efficiency using co-culture with the packaging cell line or co-culture with
      the MS-5 cell line plus viral supernatant. However, in the presence of MS-5, a
      much higher proportion of CFU-S (70% versus 30%) had radioprotective properties,
      suggesting an important role for the stromal cells in the maintenance of
      hematopoietic reconstituting ability. Finally, G418 selection, even for a limited
      period (24 h), significantly decreased the radioprotective capacities of CFU-S
      (56% versus 18%). Subsequently, hematopoietic reconstitution by single CFU-S was
      quantified in recipient mice. The progeny of CFU-S were found at a significant
      level in the blood, spleen and bone marrow in 38% and 15% of mice, 1 and 3 months
      after transplantation, respectively. These results demonstrate that we have
      substantially improved the infection protocol. Under these conditions of
      infection, it is possible to conserve CFU-S properties and to transduce a gene
      into a stem cell with short-term hematopoietic reconstitution potential.

PMID- 8875224
TI  - Restoration of hexosaminidase A activity in human Tay-Sachs fibroblasts via
      adenoviral vector-mediated gene transfer.
AB  - Tay-Sachs disease (TSD) is a lysosomal storage disease due to hexosaminidase A
      deficiency caused by mutations in the gene for alpha-chain (Hex alpha). A human
      Hex alpha cDNA was subcloned into the adenoviral plasmid pAdRSV. Hex alpha.
      Replication-deficient adenovirus was generated by homologous recombination in 293
      cells. Human fibroblasts from a patient suffering from TSD were infected with the
      recombinant adenovirus. TSD fibroblasts expressing the recombinant alpha-chain
      had an enzyme activity on the natural substrate ranging from 40 to 84% of the
      normal. The corrected cells secreted up to 25 times more Hex alpha than control
      fibroblasts. The Hex alpha encoded by the adenovirus was shown to be correctly
      transported into the lysosomes and to normalize the impaired degradation of GM2
      ganglioside in TSD fibroblasts.

PMID- 8875225
TI  - Surfactant enhances adenovirus-mediated gene expression in rabbit lungs.
AB  - The efficiency and localization of gene transfer for gene therapy in the lung
      will depend on vector selection and technique used to deliver the vector. We
      hypothesized that surfactant might facilitate gene transfer because of its
      biophysical properties that enhance spreading of saline suspensions in the
      airways. We used a replication defective adenovirus directing the expression of
      the luciferase reporter gene at different virus doses and surfactant
      concentrations and instilled 4 ml suspensions into the lungs of adult rabbits.
      Transgene expression measured as luciferase-dependent light units in tissue
      homogenates 3 days after instillation had similar lobar distributions for
      surfactant-viral suspensions and for phosphate-buffered saline viral suspensions.
      However, total light units were four- to six-fold increased for viral doses of <
      10(10) plaque forming units in 10 mg/ml or 25 mg/ml surfactant suspensions. The
      percentage of total transgene expression in the tracheacarina-bronchus decreased
      from over 50% to about 10% for virus instilled with surfactant concentrations of
      2 mg/ml or greater, indicating preferential expression in airway epithelial cells
      located more distally in the lung. Surfactant did not enhance persistence of
      transgene expression 7 or 14 days after instillation. Surfactant facilitates
      adenovirally mediated gene transfer in the peripheral lung and enhances transgene
      expression.

PMID- 8875226
TI  - Analysis of the relative level of gene expression from different retroviral
      vectors used for gene therapy.
AB  - We have analyzed the relative level of gene expression and viral titer from
      different types of retroviral vectors used for gene therapy, the LTR-based MFG
      vector and the internal promoter-containing vectors, LNCX, LNSX and LXSN. The CAT
      gene was used for comparison of retroviral vector gene expression in both
      transfected and transduced cells, while the neo gene was used to evaluate viral
      liter. In transfected cells, MFG-CAT expressed higher levels of CAT then the
      other vectors, LNC-CAT was next, while L-CAT-SN and LNS-CAT produced much lower
      levels. CAT expression from MFG-CAT was particularly high in the human T lymphoid
      cell lines CEM-SS and H9. In nonselected transduced cells. CAT expression from
      MFG was 10- to 50-fold higher than with the other vectors. Similar observations
      were made with retroviral constructs expressing human EPO and murine GM-CSF. In
      transient transfection assays, the titer of MFG was at least five-fold higher
      than the other vectors as determined by Southern analysis and G418 resistance.
      Analysis of the steady-state RNAs produced after transfection of the packaging
      cell lines showed that MFG expressed a significantly higher level of genomic RNA,
      which contains the packaging signal, than the other vectors while still
      expressing a high level of the subgenomic RNA encoding CAT. The high level of
      genomic RNA most likely contributes directly to the higher titer of MFG. We also
      compared viral titers from subcloned PA317 producer lines containing LNC-CAT and
      MFG-CAT-Neo, and confirmed that the titer of the MFG virus was higher than that
      of the LNCX. In selected subcloned transduced NIH3T3 cells, average levels of CAT
      activity were nine-fold higher from MFG-based vector. Our results suggest that
      there are significant differences in both the titer and the level of gene
      expression between retroviral vectors which are currently being used in gene
      therapy clinical trials.

PMID- 8875227
TI  - Effect of amniotic fluid on cationic lipid mediated transfection and retroviral
      infection.
AB  - In preparation for foetal gene therapy by intra-amniotic gene application, we
      have investigated the effect of amniotic fluid on several gene transfer systems.
      In vitro lipofection of embryonically derived 3T3 cells by several of the tested
      cationic lipids decreases in the presence of human amniotic fluid, while two
      formulations, Lipid 67 and Tfx-50, remain highly active. As some body fluids are
      known to inactivate most retroviral vectors, we investigated the influence of
      amniotic fluid on the efficiency of infection of 3T3 cells by murine leukaemia
      virus (MoMLV)-based vectors, including amphotropic and ecotropic retrovirus, and
      a vesicular stomatitis virus G (VSV-G) glycoprotein pseudotyped retroviral
      vector. All showed a decrease of infectivity from 21 to 56% in the presence of
      amniotic fluid. The ecotropic retrovirus is the most infectious under normal
      conditions as well as in amniotic fluid. Our results suggest that intra-amniotic
      injection may allow efficient gene transfer using either amniotic fluid-resistant
      cationic lipids or ecotropic retroviral vectors in a murine in vivo model for
      foetal gene therapy. The VSV-G-pseudotyped vector, although displaying a decrease
      of infectivity, remains of great interest for gene delivery, because of its broad
      host range and because of the high virus titers achievable. Finally, a
      baculovirus-based vector shows no decrease of its infectivity and does not seem
      to be affected by amniotic fluid but has only low infectivity on the tested
      foetal fibroblast cell line.

PMID- 8875228
TI  - A demonstration using mouse models that successful gene therapy for cystic
      fibrosis requires only partial gene correction.
AB  - Quantifying the level of transgene expression necessary for phenotypic effect is
      an important consideration in designing somatic gene therapy protocols. A
      nonlinear relationship between phenotype and gene activity is predicted by
      control analysis for any autosomal recessive condition. The unaffected phenotype
      of heterozygotes for autosomal recessive disorders demonstrates that 50% of the
      normal level of gene expression is sufficient to prevent disease. By extension,
      an exaggerated and positive effect on the mutant phenotype is predicted to arise
      from only a small addition of normal transgene expression delivered by gene
      therapy. We tested this expectation directly by intercrossing mice carrying
      different Cftr alleles which modulate Cftr gene expression from 0 to 100%. We
      demonstrate that 5% of the normal level of Cftr gene expression results in a
      disproportionately large correction of the chloride ion transport defect (50% of
      normal) and essentially complete rescue of the intestinal disease (100%
      survival). It follows that even modest levels of transgene expression and only
      partial correction of CFTR channel activity may have a significant clinical
      impact.

PMID- 8875229
TI  - Evaluation of promoter strength for hepatic gene expression in vivo following
      adenovirus-mediated gene transfer.
AB  - Transgene expression in studies of both gene function and gene therapy may be
      assisted considerably through the use of transcriptional regulatory elements
      which permit high-level, and/or tissue-specific gene expression. We have
      therefore evaluated the transcriptional activities of a series of viral and
      cellular enhancer/promoter elements, both in vitro and in vivo. The five
      enhancer/promoter elements showing either high-level or hepatocyte-specific
      expression following transient transfection into hepatoma cells were incorporated
      into recombinant adenoviruses expressing human alpha 1-antitrypsin (hAAT) for in
      vivo studies in the liver of immunodeficient and immunocompetent mice. The human
      elongation factor 1 alpha gene promoter produced 2 mg/ml serum level of hAAT,
      which is physiologic in humans and will be therapeutic for patients with AAT
      deficiency. This and all other enhancer/promoters except that of the CMV-IE gene
      yielded persistent hAAT expression in SCID mice. These findings demonstrate that
      adenovirus vectors provide an effective system for studies designed to evaluate
      enhancer/promoter activities in vivo. Several of the enhancer/promoters examined
      in this study will have significant utility in adenovirus-mediated gene therapy
      for alpha 1-antitrypsin deficiency and other genetic disorders.

PMID- 8875230
TI  - Gradient of RGD-dependent entry of adenoviral vector in nasal and intrapulmonary
      epithelia: implications for gene therapy of cystic fibrosis.
AB  - The efficiency with which adenoviral vectors infect airway epithelial cells in
      vivo is unclear despite extensive preclinical and clinical studies. Our
      hypothesis is that gene transfer is limited by vector internalization which is
      mediated by binding of a fiber with a cellular receptor and the RGD motif of the
      penton base of the virus with cellular alpha v beta integrin. Experiments in mice
      demonstrate an anatomical gradient of susceptibility to adenoviral vector
      mediated gene transfer with epithelia of proximal structures, such as nose and
      trachea, much less infectable than the distal noncartilaginous airway. Throughout
      the airway, gene transfer is dependent on RGD-mediated interactions which are
      rate limiting in the distal lung. A panel of tissues from cystic fibrosis and non
      cystic fibrosis patients was analyzed for expression of alpha v beta 5 integrin
      which is capable of mediating RGD-dependent uptake of vector. Luminal epithelial
      cells of the nose and trachea were void of alpha v beta 5 expression whereas
      abundant expression of this integrin was present in virtually all epithelial
      cells of distal conducting airway. These findings could explain difficulties we
      and others have had in correcting the functional deficit of cystic fibrosis nasal
      epithelia and suggest that gene transfer efficiency may be greater in distal
      human lung.

PMID- 8875231
TI  - Depletion of naive T cells of the peripheral lymph nodes abrogates systemic
      antitumor protection conferred by IL-2 secreting cancer vaccines.
AB  - It has been postulated that IL-2 secreting cancer vaccines establish antitumor
      immunity because the cytokine acting in a paracrine fashion would deliver a
      helper signal directly to the T cells making contact with the modified tumor
      cells at the site of vaccination. However, patterns of lymphocyte recirculation
      cannot be reconciled with the above direct interaction model: only primed memory
      T cells rather than naive T lymphocytes patrol the periphery, while naive T cells
      travel to the peripheral lymph nodes, where priming occurs. We have found that in
      vivo treatment of mice with the antibody MEL-14 directed against L-selectin,
      which is a molecule expressed at high levels on naive T cells, can completely
      abrogate protection against a mouse melanoma conferred by an IL-2 secreting
      vaccine. Since mouse memory CD4 and CD8 T cells are L-selectin-low, only
      migration of naive T cells is perturbed by the in vivo antibody blockade. Thus,
      priming of naive T cells in the draining lymph node is a critical step for the
      successful vaccination by IL-2 secreting cancer vaccines. Such priming is
      performed most efficiently by professional antigen presenting cells;
      consequently, these data also imply that allogeneic origin of tumor vaccines may
      not exclude successful vaccination.

PMID- 8875232
TI  - In vivo gene transfer to the human biliary tract.
AB  - The human biliary tract offers an excellent model for gene transfer studies for a
      variety of diseases localized to the liver. The aim of this study was to
      determine if a viable liver might be employed to study viral transfection of the
      human biliary system in order to mimic in vivo human experiments. Using a normal
      human liver initially procured for transplantation, but subsequently found
      unsuitable, and with an intact biliary tree, the hepatic vascular supply was
      accessed for continuous perfusion. The common and left hepatic biliary system was
      isolated by balloon catheterization. A replication defective adenoviral vector
      containing the Escherichia coli beta-galactosidase (lac Z) reporter gene
      (AdCMVLacZ) was injected into the catheter-isolated left and common bile duct
      lumen. Viral exposure to the right duct system was prevented by ligation. The
      bile duct segments were excised and prepared for enzymatic (X-gal) staining.
      Intense staining was observed in the biliary epithelium exposed to the adenoviral
      vector. No evidence of beta-galactosidase staining was noted in the unexposed
      biliary mucosa. We report direct transfection of biliary epithelial cells from
      normal human liver with a recombinant adenovirus. Our data suggest potential
      therapeutic applications for gene therapy of hepatobiliary disorders.

PMID- 8875233
TI  - Incorporation of nuclear matrix attachment regions into the herpes simplex virus
      type 1 genome does not induce long-term expression of a foreign gene during
      latency.
AB  - The nuclear matrix plays a critical role in DNA replication, gene transcription
      and RNA processing. Transcriptionally active genes are usually associated with
      the nuclear matrix through DNA sequences, matrix attachment regions or MARs,
      which tether looped DNA to the matrix. In stable transfection and in transgenic
      mice MAR elements placed at the flanks of genic constructs may enhance expression
      and insulate against position effect variability, suggesting that independent
      units of transcription are established insulated from the regulatory controls of
      their neighbors. Herpes simplex virus type 1 (HSV-1) establishes lifelong latency
      in the infected host. Latency repression of viral genes extends to foreign genes
      incorporated into the viral genome. We report here a test of the hypothesis that
      MAR elements, flanking a foreign gene in the HSV-1 genome, would act to insulate
      it from latency repression, achieving long-term expression. A recombinant virus
      was produced which has an expression construct inserted into the HSV-1 genome at
      the Us3 locus. The expression construct consists of the A MAR element on one
      flank, an HIV-LRT driving the lacZ gene and the B MAR element on the other flank.
      The A MAR element is a 3 kb pair fragment of the 5' portion of the chicken
      lysozyme gene and the B MAR element is a 2.6 kb pair fragment from the 5' end of
      the human beta-globin gene locus control region. The LTR is derived from a human
      immunodeficiency virus isolated from the brain of an AIDS patient. Virus was
      stereotactically injected in the hippocampus, olfactory bulb and striatum of rat
      brains. Intense blue reaction product indicating beta-galactosidase activity was
      found in cells in each injected area at 2 days after injection. At 14 days after
      injection beta-galactosidase activity was no longer detected at any of the
      injected sites. We conclude that the MAR element construct did not escape latency
      repression.

PMID- 8875234
TI  - Plasmid DNA molecules complexed with cationic liposomes are protected from
      degradation by nucleases and shearing by aerosolisation.
AB  - The cationic liposome DOTAP was complexed with plasmid DNA encoding beta
      galactosidase in various ratios. As the concentration of DOTAP increased, the DNA
      became increasingly refractory to staining with ethidium bromide, presumably
      because the DNA was becoming condensed and being encapsulated by the liposomes.
      Transfection by DNA-DOTAP complexes at all ratios tested was unaffected by
      treatment of the complexes with DNase I. This finding has relevance to clinical
      trials for gene therapy of cystic fibrosis, in which patients are normally
      removed from treatment with DNase before receiving administration of DNA. We
      additionally tested the effect of aerosolisation of the liposome-DNA complex and
      of the DNA alone on the efficiency of in vitro transfection. Aerosolised DNA
      complexed with fresh DOTAP led to much lower reporter gene expression in Cos 7
      cells than non-aerosolised complex, since aerosolisation appeared to destroy
      almost all of the plasmid. However, complexing the plasmid before passage through
      the nebuliser did protect most of the DNA from degradation, as reflected in the
      levels of transfection obtained. These findings contribute towards an overall
      understanding of both how DNA-cationic liposome complexes are formed and their
      fate following administration in vivo.

PMID- 8875235
TI  - Genomic instability in 1p and human malignancies.
AB  - Both cytogenetic and molecular genetic approaches have unveiled non-random
      genomic alterations in 1p associated with a number of human malignancies. These
      have been interpreted to suggest the existence of cancer-related genes in 1p.
      Earlier studies had employed chromosome analysis or used molecular probes mapped
      by in situ hybridization. Further, studies of the various tumor types often
      involved different molecular probes that had been mapped by different technical
      approaches, like linkage analysis, radioactive or fluorescence in situ
      hybridization, or by employing a panel of mouse x human radiation reduced somatic
      cell hybrids. The lack of maps fully integrating all loci has complicated the
      generation of a comparative and coherent picture of 1p damage in human
      malignancies even among different studies on the same tumor type. Only recently
      has the availability of genetically mapped, highly polymorphic loci at (CA)n
      repeats with sufficient linear density made it possible to scan genomic regions
      in different types of tumors readily by polymerase chain reaction (PCR) with a
      standard set of molecular probes. This paper aims at presenting an up-to-date
      picture of the association of 1p alterations with different human cancers and
      compiles the corresponding literature. From this it will emerge that the pattern
      of alterations in individual tumor types can be complex and that a stringent
      molecular and functional definition of the role that Ip alterations might have in
      tumorigenesis will require a more detailed analysis of the genomic regions
      involved.

PMID- 8875236
TI  - Role of telomeric sequences in murine radiation-induced myeloid leukaemia.
AB  - A previous study indicated that a highly inbred CBA/H mouse colony contained four
      genotypic variants for telomere-like repeat (TLR) sequence arrays and that one
      variant subpopulation that constituted 20% of the colony contributed the vast
      majority (> 90%) of radiation-induced acute myeloid leukaemias (AMLs). Through
      screening of a satellite CBA/H colony and rescreening of the original colony, we
      show that, whereas germline telomere sequence polymorphism is frequent in CBA/H
      mice, there is no genetic link between a specific TLR locus variant and
      susceptibility to AML. Studies on telomere-hybridising fragments between 200 bp
      and 150 kb revealed that the germline telomere mutation frequency was highest for
      restriction fragments > 50 kb. The hypervariability of these high-molecular
      weight fragments resulted in each CBA/H mouse from the highly inbred colony
      having a different genotype. Although it was not possible to ascribe a specific
      somatic telomere mutation to AML development, telomere rearrangements were common
      in induced AMLs. Some terminal telomere-hybridising restriction fragments were
      shortened in AML samples in comparison with normal tissue, but, insofar as the
      reduction in size was relatively small, it seems unlikely that telomere erosion
      is a major contributor to the molecular pathology of murine radiation-induced
      AML.

PMID- 8875237
TI  - Microsatellite analysis of recurrent chromosome 2 deletions in acute myeloid
      leukaemia induced by radiation in F1 hybrid mice.
AB  - Deletions and/or rearrangements involving one copy of chromosome 2 are consistent
      and early events in the development of murine acute myeloid leukaemia (AML) by
      radiation. More than 90% of AMLs induced in the CBA strain of mice express such
      cytogenetic alterations, with chromosome 2 breakpoints clustering in the C and F
      regions of the chromosome. In inbred mouse strains, the molecular resolution of
      these breakpoints is problematic. However, by using x-ray-induced AMLs in FI
      progeny of genetically divergent CBA/H x C57BI, it has been possible to show
      region-specific loss of heterozygosity (LOH) in genetically linked sets of
      chromosome 2 microsatellite alleles from one of the two parental chromosomes. In
      the majority of cases, an acceptable concordance was shown for AML chromosome 2
      deletion, as defined by microsatellites and as revealed by G-band cytogenetics. A
      degree of breakpoint clustering was found, but the identification of a number of
      deletion types, based on the position of proximal and distal breakpoints as
      defined by microsatellite analysis, strongly supports a leukaemogenic mechanism
      involving gene deletion. No bias towards loss of CBA or C57BI alleles was
      observed, and the gender of AML-presenting animals did not appear to influence
      the parental origin of the deletions. A molecular map of chromosome 2 breakpoints
      has now been established in FI AMLs as a first step towards the molecular cloning
      of breakpoint sequences.

PMID- 8875238
TI  - Long-range chromatin analysis of the human MYC locus by pulsed-field gel
      electrophoresis.
AB  - The identification of cis-acting regulatory elements has been greatly facilitated
      by the perception that nonnucleosomal regions of chromatin, including sites where
      transacting factors are bound, are hypersensitive to cleavage by nucleases.
      Hence, mapping of DNaseI-hypersensitive sites (HSs) has become particularly
      valuable for the detection of transcriptional control elements. The utility of
      this technique, however, may be constrained by the huge size of some eukaryotic
      gene domains or by the nonavailability of genomic probes. Apparently, both of
      these drawbacks hold true for the human protooncogene MYC. To overcome these
      limitations, we investigated the feasibility of mapping DNaseI-HSs in large
      restriction fragments. By using MYC-amplified cell lines, we devised a simple
      protocol that allowed for the detection of DNaseI-HSs at a distance of several
      hundred kb. In an attempt to identify additional regulatory elements required for
      MYC expression, we used this method to establish the long-range chromatin
      structure of four MYC amplicons. This method has potential benefits and
      applications.

PMID- 8875239
TI  - Detection of the t(2;13) chromosomal translocation in alveolar rhabdomyosarcoma
      using the reverse transcriptase-polymerase chain reaction.
AB  - Rhabdomyosarcoma, a small-, round-cell tumor of skeletal muscle, is the most
      common soft tissue sarcoma found in children. A specific and unique chromosomal
      translocation, t(2;13)(q35;q14), has been described cytogenetically in a subset
      of these tumors and is most often associated with the alveolar histologic
      subtype. The cloning and sequencing of complementary DNA from fusion transcripts
      expressed by both cell lines and tumors have shown that this chromosomal
      translocation results in the fusion of the PAX3 gene on chromosome 2 with a
      member of the forkhead gene family, FKHR, on chromosome 13. To detect this
      genetic abnormality we have developed a sensitive method which relies on a
      reverse transcriptase-polymerase chain reaction with primers designed to be
      specific for the chromosome 2 and chromosome 13 sides of the translocation. The
      utility of this approach was tested by analyzing a series of rhabdomyosarcoma
      cell lines and tumor samples. The data demonstrate that the transcripts derived
      from the t(2;13) were restricted to tumors having features of the alveolar
      subtype and that they could be detected with greater ease and sensitivity than
      with cytogenetic analysis. This approach will facilitate a large-scale group
      effort to determine the frequency as well as the prognostic and diagnostic
      significance of this chromosomal rearrangement.

PMID- 8875240
TI  - Successful use of the same slide for consecutive fluorescence in situ
      hybridization experiments.
AB  - The feasibility of using the same slide repeatedly for fluorescence in situ
      hybridization (FISH) experiments was systematically evaluated by applying
      standard procedures and various combinations of direct- and indirect-labeled
      probes to slides from patients with hematologic malignancies. Specific and
      distinct hybridization signals along with weak background signals and chromosome
      morphology of good to moderate quality could be obtained in up to three
      experiments performed consecutively on the same slide. Signals related to biotin-
      or digoxigenin-labeled probes applied in previous hybridizations were still
      visible with variable intensity, but interpretation problems that may result from
      this signal noise can be avoided by using adequate probes, detection systems and
      fluorochromes, and sequence of experiments.

PMID- 8875241
TI  - Role of genomic instability in meningioma progression.
AB  - Microsatellite length instability, probably resulting from defective DNA mismatch
      repair mechanisms, has been described in a variety of cancers. Such genetic
      instability may play a significant role in tumor formation and progression. To
      investigate the role of microsatellite alterations in meningioma tumorigenesis
      and progression, we examined 33 microsatellite markers on nine chromosomes for
      abnormalities in 18 benign, 15 atypical, and 11 malignant meningiomas. In each
      tumor, at least 15 markers were investigated. Microsatellite instability was not
      detected in any of the cases examined. However, loss of heterozygosity for
      markers from various chromosomes was seen frequently among atypical and malignant
      meningiomas. Although some of these chromosomal losses might represent random
      events, our data also indicate a role for specific loci on chromosome arms 14q,
      1p, 10q, and possibly 9p in the development of malignancy in meningiomas. Our
      results argue against a significant role for a generalized microsatellite
      instability phenotype in meningiomas, but they suggest that genomic instability
      resulting in frequent allelic deletions may contribute to meningioma progression.

PMID- 8875242
TI  - Treacher Collins syndrome.
AB  - Treacher Collins syndrome is an autosomal dominant disorder of craniofacial
      development, the features of which include conductive hearing loss and cleft
      palate. In the absence of a candidate gene, a positional cloning approach has
      been used to isolate the mutated gene which maps to chromosome 5q31.3-32.
      Flanking markers were identified and a yeast artificial chromosome and cosmid
      contig of the region defined by these markers was created as a prelude to the
      creation of a transcript map of the region. Analysis of genes isolated using this
      approach resulted in the identification of the mutated gene. While the function
      of the gene remains unknown, the identification of 20 mutations spread throughout
      the gene, all of which would result in the insertion of a premature termination
      codon into the reading frame, suggests that the mechanism underlying the disease
      is haploinsufficiency.

PMID- 8875243
TI  - Applications of gene therapy to the CNS.
AB  - Gene therapy is a new method with potential for treating a broad range of
      acquired and inherited neurologic diseases, where the causative gene defect or
      deletion has been identified. In addition to gene replacement the application of
      gene products that reduce cellular dysfunction or death represent new therapeutic
      options. Gene transfer techniques to express novel proteins using different viral
      vectors in vitro and in vivo, as well as animal models and human trials will be
      reviewed in this article. We will focus on a new lentiviral vector as a recent
      gene transfer method and degenerative disorders of the CNS, and their related
      model systems.

PMID- 8875244
TI  - Genetic analysis of atherosclerosis: a research paradigm for the common chronic
      diseases.
AB  - Rapid discoveries of novel and unexpected disease-associated genes for
      atherosclerotic coronary artery disease (CAD) are anticipated as genomic maps
      become more detailed and methods for mapping complex disease phenotypes become
      more refined. Although establishing association or linkage of a marker locus to a
      CAD susceptibility gene is an important first step, the long-term goal should be
      to define the underlying functional mutations and explore possible disease
      mechanisms, including the gene-environment interactions that culminate in
      clinically apparent disease. This review will define a contemporary research
      paradigm for study of the genetics of CAD and other common chronic diseases using
      the tools of modern molecular biology and human genetics.

PMID- 8875245
TI  - Down syndrome genetics: unravelling a multifactorial disorder.
AB  - Down syndrome is a common disorder affecting many tissues both during development
      and later on in adult life; the principle feature of all cases is a specific form
      of mental retardation, which is combined with a range of variable traits. Down
      syndrome is an aneuploidy syndrome that is caused by trisomy for human chromosome
      21. While the phenotype is most likely due to a subtle increase in gene dosage of
      only a small minority of the estimated 500-800 genes that are present on this
      chromosome, the molecular genetics of Down syndrome remains speculative. However,
      recent advances on a number of fronts, including chromosome studies, gene
      identification and mouse modelling, are giving us the tools to dissect this
      multifactorial gene dosage disorder.

PMID- 8875246
TI  - Myotonic dystrophy: will the real gene please step forward!
AB  - The mutation underlying myotonic dystrophy (DM) was identified at the end of 1991
      amidst great rejoicing from the patients supporting the research and, not least,
      from those who spent so long searching for it. Subsequently, the molecular
      genetic phenomena associated with DM have been clearly explained by the
      transmission behaviour of the expanding repeat, which remains the only mutation
      that has been described in patients. We understand the molecular basis of
      anticipation, why the severe congenital form is almost exclusively transmitted by
      affected mothers and we have widely accepted models of the population genetics of
      DM. Yet, despite all these clearly explained molecular events, we appear to be
      hardly any closer to understanding the molecular pathology of DM than when the
      mutation was first identified. To understand the reason for this, we have to look
      in detail at the mutation itself, and in particular at the locus and its complex
      nuances. In doing so, we begin to realise that DM is unique amongst the
      Mendelianly inherited disorders, in that the mutation, because of its location in
      a very gene-rich region of the genome, probably simultaneously renders several
      genes dysfunctional. The somatic heterogeneity of the repeat, coupled with the
      involvement of several genes, accounts for the pleiotropy observed in the
      phenotype. Added to this complexity is the uncertainty of the level at which gene
      dysfunction or gain of function is occurring. It is possibly at the level of
      DNA/chromatin structure and/or RNA regulation/processing, and all of these
      pathways may, in different tissues, contribute to the final phenotype.

PMID- 8875247
TI  - Unravelling the genetics of vesicoureteric reflux: a common familial disorder.
AB  - Primary vesicoureteric reflux (VUR) is one of the more common genetic disorders.
      Little is yet known about the genetics of this potentially manageable childhood
      condition, which is characterised by regurgitation of urine from the bladder to
      the kidney. The VUR phenotype is associated with shortness of the submucosal
      segment of the ureter due to congenital lateral ectopia of the ureteric orifice.
      VUR is found in 30-50% of infants and young children with a urinary tract
      infection. A serious concern in families with an affected patient is that
      approximately one half of siblings or offspring will be affected, but up to a
      half of these affected siblings and offspring may be asymptomatic in childhood.
      If left untreated, these patients may present later in life with proteinuria,
      hypertension or renal failure. VUR is the commonest cause of end-stage renal
      failure in children, and an important cause in adults. As the kidney damage
      resulting from severe VUR is preventable, early detection is desirable. The
      techniques for clinical diagnosis are invasive and costly, reinforcing the
      importance of identification of a gene for VUR to facilitate genetic screening.
      Although family studies suggest a major dominant gene, the inheritance pattern is
      still a matter of debate. In rare instances, VUR occurs in association with other
      diseases, such as the coloboma-ureteric-renal syndrome, which is caused by a PAX2
      gene mutation. In this review, we present evidence that this common disorder may
      be caused by mutations in the developmental pathway of which the PAX2 gene forms
      a part.

PMID- 8875249
TI  - Quality not quantity: the pufferfish genome.
AB  - The genome of the pufferfish, Fugu rubripes (Fugu) is compact. With a similar
      gene complement to mammals and a genome size of just 400 Mb, gene density is high
      averaging one every 6-7 kb. Initial characterization of this genome has shown
      that although genes are much smaller and more densely spaced, their intron/exon
      structure is conserved with the resulting introns being small. There is little
      repetitive DNA in the genome and this greatly facilitates comparative genomic
      studies. The coding content of genes is highly conserved as are critical
      regulatory elements of some genes. Other DNA is not, however, and this allows the
      identification of homologous coding sequence between Fugu and mammalian genes.
      Although the genome of Fugu is 7.5 times smaller than the human genome, not all
      genes are reduced proportionately. Some regions of the genome show conserved
      synteny with mammalian genomes, although at the present time only short physical
      distances have been examined. The structure of the genome is also being studied.
      Initial data suggest that this may be different to that found in mammals. It is
      not clear that the same kind of isochore structure is present in this early
      vertebrate genome. Patterns of methylation may be different resulting in a
      different distribution of CpG islands. An attempt is being made to centralize
      both resources and data from the genome of Fugu so that everything may be
      integrated into a single, publicly accessible database which in turn, may be
      integrated with databases from other organisms.

PMID- 8875248
TI  - Huntington disease: new insights into the relationship between CAG expansion and
      disease.
AB  - The mutation underlying Huntington disease (HD) is CAG expansion beyond 35
      repeats within a novel gene. Recently, new insights into the role of the HD
      protein (huntingtin) in the pathogenesis of HD have emerged. The CAG is
      translated and expression of mutant huntingtin is essential for neuronal death.
      Huntingtin is crucial for normal development and may be regarded as a cell
      survival gene. Huntingtin is specifically cleaved during apoptosis by a key
      cysteine protease, apopain, known to play a pivotal role in apoptotic cell death.
      The rate of cleavage is enhanced by longer polyglutamine tracts, suggesting that
      inappropriate apoptosis underlies HD. Recently, three proteins have been
      identified and have been shown specifically to interact with huntingtin, two of
      these interactions being influenced by CAG length. Several different approaches
      to develop an animal model for HD include cDNA and YAC transgenics, as well as
      'knock-in' strategies. Such a model will be critical for the understanding of the
      natural history of HD and for the testing of new therapeutic modalities.

PMID- 8875250
TI  - Panning for gold: genome-wide scanning for linkage in type 1 diabetes.
AB  - Genome-wide scans for linkage of chromosome regions to type 1 diabetes in
      affected sib pair families have revealed that the major susceptibility locus
      resides within the major histocompatibility complex (MHC) on chromosome 6p21
      (lambda S = 2.4). It is recognized that the MHC contains multiple susceptibility
      loci (referred to collectively as IDDM1), including the class II antigen receptor
      genes, which control the major pathological feature of the disease: T-lymphocyte
      mediated autoimmune destruction of the insulin-producing pancreatic beta cells.
      However, the MHC genes, and a second locus, the insulin gene minisatellite on
      chromosome 11p15 (IDDM2; lambda S = 1.25), cannot account for all of the observed
      clustering of disease in families (lambda S = 15), and the scans suggested the
      presence of other susceptibility loci scattered throughout the genome. There are
      four additional loci for which there is currently sufficient evidence from
      linkage and association studies to justify fine mapping experiments: IDDM4
      (FGF3/11q13), IDDM5 (ESR/6q22), IDDM8 (D6S281/6q27) and IDDM12 (CTLA-4/2q33).
      IDDM4, 5 and 8 were detected by genome scanning, and IDDM12 by a candidate gene
      strategy. Seven other named loci are not discounted but remain to be replicated
      widely. Multiple susceptibility loci were expected as genome-wide scans of the
      mouse model of type 1 diabetes had shown that although the MHC is the major mouse
      locus, at least 13 genes unlinked to the MHC are involved in the development of
      disease. Genome-wide scans using 1000 affected sibpair families will be required
      to be confident that all genes with effects on familial clustering equivalent to
      the insulin gene locus (lambda S = 1.25) have been detected. The identification
      of aetiological determinants requires exclusion of hitchhiking polymorphisms in
      regions of linkage disequilibrium, as demonstrated for the MHC and the insulin
      gene loci, and functional studies implicating the disease-associated variant in
      pathogenesis. Ultimately, targeting of specific candidate mutations in mice by
      homologous recombination and replacement will be necessary to prove the primary
      role of any candidate mutation.

PMID- 8875251
TI  - The presenilin genes: a new gene family involved in Alzheimer disease pathology.
AB  - A positional cloning approach has led to the identification of two closely
      related genes, the presenilins (PS), for autosomal dominant presenile Alzheimer
      disease (AD): PS-1 at 14q24.3 and PS-2 at 1q31-q42. The PS-1 gene was identified
      by direct cDNA selection of yeast artificial chromosomes containing the candidate
      chromosomal region. Subsequently, the PS-2 gene was identified due to its high
      sequence homology with PS-1 and its location within the candidate region defined
      by linkage studies. To date, 30 different missense mutations and one in-frame
      splice site mutation were described in PS-1, while only two missense mutations
      were detected in PS-2, suggesting that PS-1 mutations are more frequently
      involved in familial presenile AD. The PS transcripts encode novel proteins that
      resemble integral transmembrane proteins of roughly 450 amino acids and at least
      seven transmembrane domains. The genomic organization of the PS genes is very
      similar showing that full length PS-1 and PS-2 are encoded by 10 exons. However,
      different alternative splicing patterns have been observed for PS-1 and PS-2
      indicating that the corresponding proteins (ps-1 and ps-2) may have similar but
      not identical biological functions.

PMID- 8875252
TI  - Molecular genetics of Bloom's syndrome.
AB  - Mutation of the Bloom's syndrome (BS) gene, BLM, results in genomic instability.
      As the first step toward positional cloning of the gene, tight linkage of BLM and
      FES at 15q26.1 was detected by genotyping affected in families in which the
      parents are cousins, so-called homozygosity mapping. Linkage disequilibrium
      between BLM and FES was detected in Ashkenazi Jews with BS, confirming the
      linkage results and supporting the hypothesis that the increased frequency of the
      BS mutation in the Ashkenazim is due to founder effect. The mutated BLM gene is
      inherited identical by descent in BS persons whose parents are cousins or
      Ashkenazi Jewish; in persons whose parents do not share a common ancestor, BLM
      can be mutant at different positions within the gene. In such persons, crossing
      over within BLM can occur to form a functionally wild-type gene capable of
      correcting the mutant phenotype of BS cells. In half the cases in which such
      somatic intragenic recombination had occurred, reduction to homozygosity was
      detectable distal to BLM but not proximal to it. We localized the cross-over
      points in corrected cells to a 250 kb genomic segment and isolated therefrom a
      4437 bp cDNA that encodes a 1417 amino acid protein homologous to the RecQ
      subfamily of DExH box-containing DNA and RNA helicases. The identification of BLM
      as a putative DNA helicase provides a new and powerful tool to investigate the
      primary defect in BS and the function of the BLM gene product in maintaining the
      integrity of the genome.

PMID- 8875253
TI  - Genetics of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a paralytic disorder caused by
      degeneration of motor neurons in the brain and spinal cord. Identification of
      mutations in the gene for Cu,Zn superoxide dismutase (SOD1) in a subset of ALS
      families made it possible to develop a transgenic mouse model of ALS and to
      investigate its pathogenesis. These investigations suggest that mutant SOD1 acts
      through a toxic gain of function which may involve generation of free radicals.
      Conformational change in the mutant SOD1 protein, especially the distortion of
      the 'rim' of the electrostatic guidance channel may be central to this toxic gain
      of function and to the pathogenesis of ALS.

PMID- 8875254
TI  - Transcription factor genes and the developing eye: a genetic perspective.
AB  - We review the current knowledge of transcription factors in mammallan eye
      development. The 14 transcription factors presently known to be required for eye
      formation are examined in some detail, incorporating data from both humans and
      rodents. Aspects of the biochemistry, expression patterns, genetics, mutant
      phenotypes, and biological insights acquired from the examination of loss-of
      function mutations are summarized. The other 32 tissue-restricted transcription
      factors that are currently known to be expressed in the developing or mature
      mammallan eye are tabulated, together with the timing and site of their ocular
      expression; the requirement for most of these genes in the eye is unknown.
      Contributions to mammallan eye development from the study of the genetics of the
      Drosophila eye are discussed briefly. Identification of the entire cohort of
      transcription factors required for eye development is an essential first step
      towards understanding the mechanisms underlying eye morphogenesis and
      differentiation, and the molecular basis of inherited eye abnormalities in
      humans.

PMID- 8875255
TI  - Mismatch repair defects in human carcinogenesis.
AB  - Mismatch repair defects are carcinogenic. This conclusion comes some 80 years
      after the original description of a type of familial colorectal cancer in which
      mismatch repair defects are involved, and from decades of dedicated basic science
      research into fundamental mechanisms cells use to repair their DNA. Mismatch
      repair (MMR) was described first in bacteria, later in yeast and finally in
      higher eukaryotes. In bacteria, one of its roles is the rapid repair of
      replicative errors thereby providing the genome with a 100-1000-fold level of
      protection against mutation. It also guards the genome by preventing
      recombination between non-homologous regions of DNA. The information gained from
      bacteria suddenly became relevant to human neoplasia in 1993 when the RER
      phenotype of microsatellite instability was discovered in human cancers and was
      rapidly shown to be due to defects in mismatch repair. Evidence supporting the
      role of MMR defects in carcinogenesis comes from a variety of independent sources
      including: (i) theoretical considerations of the requirement for a mutator
      phenotype as a step in multistage carcinogenesis; (ii) discovering that MMR
      defects cause a 'mutator phenotype' destabilizing endogenous expressed genes
      including those integral to carcinogenesis; (iii) finding MMR defects in the
      germline of HNPCC kindred members; (iv) finding that such defects behave as
      classic tumor suppressor genes in both familial and sporadic colorectal cancers;
      (v) discovering that MMR 'knockout' mice have an increased incidence of tumors;
      and (vi) discovering that genetic complementation of MMR defective cells
      stabilizes the MMR deficiency-associated microsatellite instability. Models of
      carcinogenesis now must integrate the concepts of a MMR defect induced mutator
      phenotype (Loeb) with the concepts of multistep colon carcinogenesis (Fearon and
      Vogelstein) and clonal heterogeneity/selection (Nowell).

PMID- 8875256
TI  - Recombination and nondisjunction in humans and flies.
AB  - Recent studies of Drosophila and humans indicate that aberrant genetic
      recombination is an important component of nondisjunction in both species. In
      both, a proportion of nondisjunction is associated with failure to pair and/or
      recombine and in both, exchanges which are either too distal or too proximal
      increase the likelihood of malsegregation. In this review we provide two
      perspectives on these observations: first, a review of exchange and chromosome
      segregation in model organisms, focusing on Drosophila, and secondly an overview
      of nondisjunction in humans. This format allows us to describe the paradigms
      developed from studies of model organisms and to ask whether these paradigms
      apply to the human situation.

PMID- 8875257
TI  - The factor IX gene as a model for analysis of human germline mutations: an
      update.
AB  - The variation generated by germline mutation is essential for evolution, but
      individuals pay a steep price in the form of Mendelian disease and genetic
      predisposition to complex disease. Indeed, the health of a species is determined
      ultimately by the rate of germline mutation. Analysis of the factor IX gene in
      patients with hemophilia B has provided insights into the human germline
      mutational process. Herein, seven topics will be reviewed with emphasis on recent
      advances: (i) proposed mechanisms of deletions, inversions, and insertions; (ii)
      discordant sex ratios of mutation and associated age effects; (iii) somatic
      mosaicism; (iv) founder effects; (v) mutation rates; (vi) the factor IX gene as a
      germline mutagen test; and (vii) cancer as a possible mechanism for maintaining a
      constant rate of germline mutation.

PMID- 8875258
TI  - Recent advances in understanding of genetic susceptibility to breast cancer.
AB  - The breast cancer susceptibility gene, BRCA1, was isolated in 1994. Recent
      investigations into the genetic epidemiology of BRCA1 have revealed an
      unexpectedly high prevalence of mutations amongst Ashkenazi Jews. Analyses of
      BRCA1 function have indicated that it may act as an inhibitor of cell
      proliferation and is necessary for normal development in the mouse. The presence
      of a motif in BRCA1 characteristic of a family of proteins known as granins, has
      led to the suggestion that the protein is secreted into the extracellular space.
      The BRCA2 gene has recently been identified. BRCA2 encodes a large protein of
      3418 amino acids without strong homology to any other protein in the database.
      However, BRCA2 also contains a putative granin motif and a different eight times
      repeated motif of unknown function. In addition to breast and ovarian cancer,
      germline BRCA2 mutations probably confer a small risk of a wide range of cancers.
      Somatic mutations of BRCA2 in sporadic breast and ovarian cancer are very rare.
      The gene for Cowden syndrome has recently been located and it will now be
      possible to assess whether it is responsible for the set of families not
      accounted for by BRCA1 and BRCA2.

PMID- 8875259
TI  - Tumours of the skin.

PMID- 8875260
TI  - Tumours of the mammary gland.

PMID- 8875261
TI  - Tumours of the oral cavity, buccal pouch, oesophagus, forestomach and salivary
      glands.

PMID- 8875262
TI  - Tumours of the liver.

PMID- 8875263
TI  - Tumours of the gallbladder.

PMID- 8875264
TI  - Tumours of the glandular stomach.

PMID- 8875265
TI  - Tumours of the intestine.

PMID- 8875266
TI  - Tumours of the pancreas.

PMID- 8875267
TI  - Tumours of the nasal cavity.

PMID- 8875268
TI  - Tumours of the lower respiratory tract.

PMID- 8875269
TI  - Tumours of the kidney.

PMID- 8875270
TI  - Tumours of the urinary bladder, renal pelvis, ureter and urethra.

PMID- 8875271
TI  - Tumours of the testis and accessory male sex glands.

PMID- 8875272
TI  - Tumours of the female genital system.

PMID- 8875273
TI  - Tumours of the endocrine glands.

PMID- 8875274
TI  - Tumours of soft tissues.

PMID- 8875275
TI  - Ultrastructure of virus-induced soft-tissue tumours.

PMID- 8875276
TI  - Tumours of the haematopoietic system.

PMID- 8875277
TI  - Tumours of the bone.

PMID- 8875278
TI  - Tumours of the nervous system.

PMID- 8875280
TI  - Quantitation of HCV viraemia by branched DNA signal amplification in patients
      treated with alpha-interferon--a longitudinal study.
AB  - Using bDNA, the plasma viral load trend of HCV-infected patients undergoing IFN
      therapy was analyzed. Nine patients were enrolled, each assigned to one of three
      groups, based on IFN response as determined by ALT and AST level trend. HCV was
      genotyped using DEIA. Each patient's clinical stage was determined by liver
      biopsy analysis. In nonresponding patients elevated viral loads and biochemical
      parameters were observed. These values were not influenced by IFN treatment. In
      relapsed patients the cessation of IFN treatment increased viral load; this was
      associated with a rise in ALT and AST values. In responders ALT and AST levels
      remained normal; viral load was low. Patients with elevated HCV viral load showed
      a worsening in their liver histology during the follow-up period. These results
      confirm that plasma viral load is a good marker of biochemical change and disease
      progression.

PMID- 8875281
TI  - Evaluation of the Glasgow Coma Scale score in critically ill infectious disease
      patients.
AB  - In this prospective study the Glasgow Coma Scale (GCS) score was evaluated in 107
      critically ill infectious disease (ID) patients admitted to the Intensive Care
      Unit (ICU) during a 1-year period. Patients were separated into two groups: those
      affected by central nervous system (CNS) infections and those affected by
      infections other than of the CNS. There were no apparent differences in the first
      ICU day GCS score values between the two groups (11 +/- 4 vs. 11 +/- 4, p =
      0.5318). Univariate logistic regression analysis confirmed a significant
      relationship between the first ICU day GCS score and the subsequent ICU mortality
      in the group of patients with CNS infections (r = 0.3152, p = 0.0015) but not in
      the group with infections not affecting the CNS (r = 0.0919, p = 0.1106). Our
      preliminary results suggest that the prognostic value of the GCS score is valid
      only in patients with CNS infections but not in other ID patients.

PMID- 8875279
TI  - Immunomodulating effects of antibiotics: literature review.
AB  - Antibiotics can interact directly with the immune system. This is a review of the
      immunomodulating effects of antibiotics. The Medline database on CD-ROM was
      searched for the years 1987 to 1994 using the following search string: "thesaurus
      explode antibiotics/all AND (thesaurus explode immune-system/drug effects OR
      thesaurus immune-tolerance/drug effects)." Aspects of the immune system studied
      were aspects of phagocyte functions: phagocytosis and killing, and chemotaxis and
      aspects of lymphocyte functions: lymphocyte proliferation, cytokine production,
      antibody production, delayed hypersensitivity and natural killer-cell activity.
      In order to quantify and to compare immunomodulatory properties of antibiotics we
      calculated an "immune index," defined as: number of positive statements--number
      of negative statements/total number of statements. Concerning phagocytosis,
      positive effects were observed for cefodizime, imipenem, cefoxitin, amphotericin
      B and clindamycin and negative effects for erythromycin, roxithromycin,
      cefotaxime, tetracycline, ampicillin and gentamicin. Clindamycin, cefoxition and
      imipenem induce enhancement of chemotaxis, whereas cefotazime, rifampicin and
      teicoplanin decrease chemotaxis. Regarding lymphocyte proliferation, cefodizime
      has the strongest stimulating effect, whereas tetracycline has the strongest
      negative effect. Except for erythromycin and amphotericin B the number of
      statements reported is too small to be conclusive for the interpretation of
      effects on cytokine production. Erythromycin and amphotericin B appear to
      stimulate cytokine production. As to antibody production, cefodizime has the
      strongest positive effect, whereas josamycin, rifampicin and tetracycline have
      marked negative effects. For delayed hypersensitivity and the natural killer-cell
      activity the number of statements is too small for any single antibiotic to be
      conclusive. There are three markedly immuno-enhancing antibiotics (imipenem,
      cefodizime and clindamycin) and eight markedly immuno-depressing antibiotics
      (erythromycin, roxithromycin, cefotaxime, tetracycline, rifampicin, gentamicin,
      teicoplanin and ampicillin).

PMID- 8875283
TI  - Chlamydial antibodies in semen: search for "silent" chlamydial infections in
      asymptomatic andrological patients.
AB  - The importance of a serological diagnostic workup in male genitourinary
      infections with Chlamydia trachomatis and its relevance for male infertility is
      still under debate. In a prospective study, antichlamydial serum and seminal
      plasma antibodies of 131 consecutive patients (mean age 31: 20-57) without
      evidence of acute urethritis and with negative urethral chlamydial culture were
      investigated. The antibody determination was carried out with a genus specific
      rELISA. In patients with positive seminal plasma IgA, chlamydial genome was
      evaluated by polymerase chain reaction (PCR). The results were associated with
      standard semen parameters according to evaluated WHO guidelines. Specific serum
      IgG antibodies were found in 51 patients (38.9%), IgA in 39 (29.7%); both
      antibodies were present in 25 patients (19%). Seminal plasma IgG was demonstrable
      in seven patients (5.3%), IgA in 26 (19.9%), and five patients were positive for
      both antibody classes (3.8%). Of the 26 men positive for specific seminal plasma
      IgA antibodies 12 did not demonstrate a serum antibody reaction. Only two
      patients with positive IgA titers in their seminal plasma showed a positive
      chlamydial genome reaction in PCR (8%). Men with antichlamydial seminal plasma
      IgA and/or IgG did not differ significantly in any of the standard semen sperm
      parameters from men testing negative for antibodies, with the exception of
      peroxidase positive leukocytes (p < 0.01), nor was there an association between
      any of the ejaculate parameters and any of the antibody titers. The data of about
      40% antichlamydial serum antibody findings without a significant association with
      seminal plasma antibodies and no clinical signs of infection seem to reflect a
      history of urogenital infection. The unique presence of seminal plasma IgA in 12
      of 26 cases may be caused by a local antibody response due to a "silent"
      infection. Thus, seminal plasma IgA was associated with signs of inflammation,
      whereas, there was no association with genome or pathogen demonstration.
      Therefore, it appears to be necessary to reevaluate genus-specific seminal plasma
      IgA antibodies with a species-specific microimmunofluorescence test and to
      compare these results with a genome screening using PCR or in situ hybridization.

PMID- 8875282
TI  - Increased serum levels of soluble tumor necrosis factor receptors (sTNF-Rs) in
      children and adolescents with vertically and horizontally transmitted HIV
      infection.
AB  - Two different receptors exist for tumor necrosis factor-alpha (TNF-alpha),
      designated as p55 (TNF-RI) and p75 (TNF-RII). Soluble (= s) forms of TNF-Rs are
      secreted after proteolytic cleavage and block the effects of TNF-alpha. sTNF-RI,
      sTNF-RII and the soluble interleukin 2 receptor (sIL-2R) were determined by ELISA
      in serum samples of HIV-infected children and adolescents. Twelve children with
      vertical HIV infection (mean age +/- SD, 5.9 +/- 3.8 years) and 17 horizontally
      infected patients (16.1 +/- 7.3 years) were classified according to the revised
      CDC criteria. Twenty healthy control persons (6.4 +/- 5.8 years) showed the
      following receptor concentrations (median): sTNF-RI 888 pg/ml, sTNF-RII 1,741
      pg/ml, sIL-2R 94 pM. Compared to controls, horizontally HIV-infected patients had
      significantly (Mann-Whitney U test) higher levels for sTNF-RI (median 1,192
      pg/ml), sTNF-RII (3,481 pg/ml) and sIL-2R (128 pM). For vertically infected
      children only sTNF-RII (2,944 pg/ml) was significantly elevated compared to
      controls. There were no differences in soluble receptor levels between vertical
      or horizontal transmission. Surprisingly, no significant differences for sTNF-RI,
      sTNF-RII and sIL-2R occurred when 19 patients in stage CDC I were compared to ten
      patients in stages II or III. The clearly elevated sTNF-RII levels in patients
      with horizontal and vertical HIV infection indicate the activation of the
      monocyte/macrophage system in both groups.

PMID- 8875284
TI  - Tumor necrosis factor alpha (TNF-alpha) and sepsis: evidence for a role in host
      defense.
AB  - Serum levels of TNF-alpha were evaluated in 29 patients with sepsis, using TNF
      alpha sensitive L929 cells (sensitivity = 15 pg/ml). Blood samples were collected
      serially at the first 24-36 h of symptoms. Seventeen patients had severe
      underlying disease and 12 patients had mild or no underlying disease. Shock was
      present in 25 patients. Overall mortality was 62.1%. TNF-alpha was detected in
      nine patients (range: 57.7-3,169 pg/ml). There was a tendency to detect TNF-alpha
      in patients with mild or no underlying disease (p = 0.07). Detection of TNF-alpha
      was associated with survival (p = 0.0003) even when adjusted for severity of
      underlying disease (p = 0.005), shock (p = 0.0005), coagulation abnormality (p =
      0.002) and immunosuppressive therapy (p = 0.005), using a bivariate analysis. In
      this investigation, detection of circulating TNF-alpha was predictive of good
      outcome in septic patients, suggesting a role for this cytokine in host-defense
      against this kind of infection.

PMID- 8875285
TI  - Funguria in cancer patients: analysis of risk factors, clinical presentation and
      outcome in 50 patients.
AB  - Fifty cancer patients with funguria of > 10(5) CFU/ml, dysuria and leukocyturia
      were retrospectively analyzed for etiology, risk factors and outcome. In 72% of
      cases Candida albicans and in 28% non-albicans Candida spp. (Candida krusei,
      Candida tropicalis) and non-Candida spp. yeasts (Blastoschizomyces capitatus)
      were isolated. Torulopsis glabrata was not found among these patients. The most
      frequent risk factors were: antibiotic therapy with more than one antibiotic
      agent (96%), concomitant fungal infection in other localizations than the urinary
      tract (36%), colonization with the same species (48%), catheterization with
      urinary catheter or nephrostomy (46%), prophylaxis with quinolones (50%) and
      previous therapy with corticosteroids (72%). Structural or anatomic malformations
      of the urinary tract (26%), neutropenia (28%), antifungal prophylaxis with azoles
      (22%), and diabetes mellitus (12%) were less frequently seen. Thirty of 36
      patients treated with systemic antifungals were cured and six were not.

PMID- 8875286
TI  - Pyrimethamine alone as prophylaxis for cerebral toxoplasmosis in patients with
      advanced HIV infection.
AB  - Prophylaxis for toxoplasma encephalitis was performed with pyrimethamine alone
      (50 mg daily) in 56 patients with advanced HIV infection. Thirty-eight patients
      were at high risk for toxoplasma encephalitis (CD4+ counts < or = 200/microliter,
      and presence of serum IgG antibodies to Toxoplasma gondii). The overall treatment
      period was 697 months (mean 12.5 +/- 12.1). During prophylaxis, only one patient
      developed toxoplasma encephalitis, four patients discontinued treatment due to
      adverse reactions. Steady state pyrimethamine plasma concentrations were measured
      by gas chromatography. Mean plasma level was 1,887 +/- 1,161 ng/ml, during liver
      enzyme-inducing comedication plasma levels were significantly (p = 0.0001)
      reduced (1,488 +/- 884 ng/ml versus 1,978 +/- 1,196 ng/ml without comedication).
      All patients received a folinic acid supplement of 7.5 mg daily. Serum folate
      levels ranged from 5.7-105 (43.7 +/- 29.2) nmol/l; severe hematological side
      effects did not occur.

PMID- 8875287
TI  - Pulmonary cryptosporidiosis in the acquired immunodeficiency syndrome.
AB  - Since the beginning of the AIDS epidemic, Cryptosporidium has emerged as a
      pathogen responsible for diarrhea in humans. Cryptosporidiosis confined to the
      respiratory tract has been documented only rarely in humans. An HIV-infected
      patient is described here, who developed pulmonary and intestinal
      cryptosporidiosis. Lung involvement was proven by biopsy, which also revealed
      bronchiolitis but no other pathogens. The patient died of respiratory failure 2
      months after the onset of respiratory symptoms.

PMID- 8875289
TI  - Extraordinary localisation of Mycobacterium tuberculosis infection.

PMID- 8875288
TI  - Immediate immunosuppression caused by acute HIV-1 infection: a fulminant
      multisystemic disease 2 days post infection.
AB  - A healthy 19-year-old woman had vaginal intercourse on a single occasion with an
      HIV-1 positive male from Gambia. Two days later she developed an acute HIV
      infection presenting as a fulminant multisystem disease that lasted for 35
      hospital days and included: immediate immunosuppression with extreme CD4+
      lymphocytopenia and combined with CD8+ lymphocytosis, neutropenia and
      hypogammaglobulinemia; intermittent spiking fever; pneumonitis; hepatitis;
      changing skin rashes; peripheral neuropathy with myopathy, and panencephalitis.
      P24 antigen was detected by Western blot on day 23 and seroconversion was
      detected by ELISA on day 25. Cultured lymphocytes from peripheral blood and
      cerebrospinal fluid grew HIV-1.

PMID- 8875290
TI  - Emerging infectious diseases in the institutional setting: another hot zone.
AB  - During the closing years of the 20th century, there has been an unprecedented
      number of newly recognized infectious agents and a resurgence of infectious
      diseases only recently thought to be conquered. These problems have been
      compounded by the increasing number of pathogens that have evolved resistance to
      antimicrobial agents. Hospitals and other institutional settings occupy a pivotal
      niche in the emergence of infectious agents due to factors such as the large
      concentrations of ill and immuno-compromised persons, evolving technologies in
      healthcare settings, routine breeches of host defense mechanisms, and frequent
      use of antimicrobial agents. Any comprehensive strategy to address emerging
      infectious diseases must incorporate provisions for healthcare settings,
      including efforts to enhance surveillance, response capacity, training,
      education, applied research, and routine implementation of prevention measures.

PMID- 8875291
TI  - Preventing the emergence of multidrug-resistant microorganisms through
      antimicrobial use controls: the complexity of the problem.
AB  - Widespread use of antimicrobials in the inpatient and outpatient setting has been
      associated with the emergence of multidrug-resistant microorganisms. A variety of
      methods exist to improve the appropriateness of antimicrobial use in the
      inpatient setting, including guidelines, antimicrobial use evaluations,
      micribiology laboratory guidance, formulary development and antimicrobial
      restriction, use of antimicrobial order or automatic stop order forms, and
      antimicrobial audits. To decrease the selective pressure that leads to
      development of pathogen resistance and to reduce antimicrobial expenditures,
      infectious disease, infection control, pharmacy, and administrative staff need to
      improve clinician use of antimicrobials through development and implementation of
      antimicrobial use committees. Through the implementation of a comprehensive,
      multidisciplinary approach to antimicrobial use and development of clinician
      education programs, inappropriate antimicrobial use can be reduced, patient care
      can be improved, and substantial cost savings can be realized.

PMID- 8875292
TI  - Automatic alerts for methicillin-resistant Staphylococcus aureus surveillance and
      control: role of a hospital information system.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an escalating
      problem in hospitals worldwide. The hospital reservoir for MRSA includes
      recognized and unrecognized colonized or infected patients, as well as previously
      colonized or infected patients readmitted to the hospital. Early and appropriate
      infection control measures (ICM) are key elements to reduce MRSA transmission and
      to control the hospital reservoir. OBJECTIVE: To describe the role of an expert
      system applied to the control of MRSA at a large medical center (1,600 beds) with
      high endemic rates. METHODS: The University Hospital of Geneva has an extended
      hospital information system (HIS), DIOGENE, structured with an open distributed
      architecture. It includes administrative, medical, nursing, and laboratory
      applications with their relational databases. Among available patient databases,
      clinical microbiology laboratory and admission-discharge-transfer (ADT) databases
      are used to generate computer alerts. A laboratory alert (lab alert) is printed
      daily in the Infection Control Program (ICP) offices, listing all patients with
      cultures positive for MRSA detected within the preceding 24 hours. Patients might
      be either newly detected patients colonized or infected with MRSA, or previously
      recognized MRSA patients having surveillance cultures. The ICP nurses
      subsequently go to the ward or call the ward personnel to implement ICM. A second
      alert, the "readmission alert," detects readmission to the hospital of any
      patient previously colonized or infected with MRSA by periodic queries (q 1 min)
      to the ADT database. The readmission alert is printed in the ICP offices, but
      also forwarded with added guidelines to the emergency room. RESULTS: During the
      first 12 months of application (July 1994 to June 1995), the lab alert detected
      an average of 4.6 isolates per day, corresponding to 314 hospital admissions (248
      patients); the use of this alert saved time for the ICP nurses by improving work
      organization. There were 438 readmission alerts (1.2 alerts per day) over the
      study period; of 347 patients screened immediately upon readmission, 114 (33%)
      were positive for MRSA carriage. Delayed recognition of readmitted MRSA carriers
      decreased significantly after the implantation of this alert; the proportion of
      MRSA patients recognized at the time of admission to the hospital increased from
      13% in 1993 to 40% in 1995 (P < .001). CONCLUSIONS: Hospital information system
      based alerts can play an important role in the surveillance and early prevention
      of MRSA transmission, and it can help to recognize patterns of colonization and
      transmission.

PMID- 8875293
TI  - Methicillin-resistant Staphylococcus aureus epidemiology and control in Belgian
      hospitals, 1991 to 1995. Groupement pour le Depistage, l'Etude et la Prevention
      des Infections Hospitalieres.
AB  - OBJECTIVES: To describe the Belgian methicillin-resistant Staphylococcus aureus
      (MRSA) surveillance network, the evolution of methods used in Belgian hospitals
      for MRSA detection and control, and MRSA incidence from 1994 to 1995. DESIGN,
      SETTING, AND PARTICIPANTS: Questionnaire surveys; infection control physicians
      from acute-care hospitals in Belgium. INTERVENTION: Publication of national
      guidelines for MRSA control in 1993. RESULTS: The participation rate in surveys
      ranged from 42% to 57% of hospitals. In 1995, 88% of participants detected MRSA
      strains by disk diffusion tests, with little improvement in standardization since
      1991. More centers employed the oxacillin agar screen method (27%), automated
      systems (29%), or a combination of methods (29%) than in 1991 (P < .005). Between
      1991 and 1995, the proportion of hospitals reporting MRSA control measures
      increased from 68% to 95% (P < .01). Practices that were used increasingly
      included patient placement in private room (from 50% to 93%, P < .01) and hand
      decontamination with antiseptic (from 43% to 87%, P < .01). The proportion of
      centers that reported screening MRSA carriers and treating them topically
      increased two- and threefold, respectively (P < .05). Surveillance data from 1994
      to 1995 showed that MRSA represented a mean of 21.3% of S aureus clinical
      isolates (range, 1.6% to 62.4%). The median incidence of nosocomial MRSA
      acquisition was 2.8 per 1,000 admissions, with a wide range (0 to 13.7 per 1,000
      admissions) across hospitals of all sizes. The median incidence decreased over
      the first three semesters of surveillance in hospitals with continuous
      participation. CONCLUSION: MRSA detection and control measures have improved in
      Belgian hospitals after publication of national guidelines. However, MRSA
      incidence rates show the persistence of nosocomial transmission, with large
      variations between centers. The national MRSA surveillance network should
      indicate whether control efforts eventually will curb the problem.

PMID- 8875294
TI  - Methicillin-resistant Staphylococcus aureus control in hospitals: the French
      experience. Association des Pays de la Loire pour l'Eviction des Infections
      Nosocomiales.
AB  - The first cases of isolation of Staphylococcus aureus resistant to methicillin in
      France were published in 1962. However, until recently, very few epidemiological
      studies or attempts to control the epidemic have been done in France. In this
      article, we present the results of a prospective study performed during a 3-month
      period in 27 hospitals of the Region des Pays de la Loire. Among the 94,605
      hospitalized patients included in the study, 0.45% (427) developed methicillin
      resistant Staphylococcus aureus (MRSA) infections, the incidence rate ranging
      from 0% to 1.2%. Thirty-four percent of MRSA-infected patients were 80 years old
      or older, 30% had been transferred from another service and 19% from another
      hospital, 56% were hospitalized at least once during the previous year, MRSA had
      been isolated at least once previously in 18% of MRSA-infected patients, 19%
      died, 16% were transferred to another service and 11% to another hospital, and
      only 32% were discharged to their homes. A poor compliance to contact isolation
      precautions was observed in all hospitals: 46% of MRSA-infected patients were
      hospitalized in a private room; gloves, masks, and gowns were worn for the care
      of 63.4%, 14%, and 42.5% of MRSA-infected patients, respectively; and handwashing
      was feasible in the rooms of 52% of the patients.

PMID- 8875295
TI  - Methicillin-resistant Staphylococcus aureus control in hospitals: the Dutch
      experience.
AB  - The Netherlands is one of the few countries where methicillin-resistant
      Staphylococcus aureus (MRSA) still is uncommon. In 1988, the Werkgroep Infectie
      Preventie (Working Party on Infection Prevention) issued guidelines on the
      control of MRSA that could be applied nationwide. The mainstay of the guideline
      is that all patients who carry MRSA are strictly isolated in single rooms. In
      1989, a surveillance study was started by the National Institute of Public Health
      and the Environment. This study showed that approximately 200 new cases of MRSA
      colonization or infection occur each year. Small outbreaks of MRSA occur
      occasionally in The Netherlands, but the surveillance data confirm the success of
      the Dutch policy.

PMID- 8875296
TI  - Host-bacteria interactions in foreign body infections.
AB  - Persistent staphylococcal infections are a major medical problem, especially when
      they occur on implanted materials or intravascular catheters. This review
      describes some of the recently discovered molecular mechanisms of Staphylococcus
      aureus attachment to host proteins coating biomedical implants. These
      interactions involve specific surface proteins, called bacterial adhesins, that
      recognize specific domains of host proteins deposited on indwelling devices, such
      as fibronectin, fibrinogen, or fibrin. Elucidation of molecular mechanisms of S
      aureus adhesion to the different host proteins may lead to the development of
      specific inhibitors blocking attachment of S aureus, which may decrease the risk
      of bacterial colonization of indwelling devices.

PMID- 8875297
TI  - How to limit the spread of Creutzfeldt-Jakob disease.
AB  - Transmissible spongiform encephalopathies are rare lethal diseases induced in
      humans and animals by unconventional agents called transmissible spongiform
      encephalopathy agents (TSEAs), virions, or prions. Several cases of iatrogenic
      Creutzfeldt-Jakob disease (CJD) have been reported in the literature after
      neurosurgery, treatment with pituitary-derived hormones, corneal grafting, and
      use of dura mater lyophilisates. In a given infected individual, TSEA-associated
      infectiousness depends on the nature of the organ: the central nervous system has
      the highest infectiousness, spleen and lymph nodes a medium infectiousness, and
      organs such as bone, skin, or skeletal muscles do not harbor any detectable
      infectiousness in experimental models. Transmissible spongiform
      encephalopathy/prions have unconventional properties; in particular, they resist
      almost all the chemical and physical processes that inactivate conventional
      viruses. Therefore, prevention of CJD agent transmission must be taken into
      account in daily hospital practice. Efficient sterilization procedures should be
      determined. In tissue and blood donation, donors with a neurologic history must
      be excluded, and patients treated with pituitary-derived hormones should be
      considered potentially infected with TSEA and excluded.

PMID- 8875298
TI  - Operative precautions in HIV and other bloodborne virus diseases.
AB  - Mathematical means have suggested that the surgical team is at particular risk of
      acquiring HIV (or other bloodborne viruses) from a source patient. To reduce this
      risk, it is mandatory to avoid accidental injuries during operative procedures.
      The surgeon must handle tissues with instruments and must minimize finger use.
      Sharp instruments should be passed through a neutral zone to ensure that the
      surgeon and nurse do not touch the same instrument at the same time. Instruments
      should not be handled blindly, but instead should be accompanied by eye and
      verbal contact. We find these changes in surgical technique are necessary for
      present and future generations of surgeons.

PMID- 8875299
TI  - AIDS, emergency operations, and infection control.
AB  - Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency
      virus (HIV) may turn out to be the largest lethal epidemic of infection ever. The
      estimated global number of HIV-infected adults in 1993 was 13 million, with
      projections of up to 40 million by the year 2000. Human immunodeficiency virus
      infections and AIDS are relevant to surgeons with respect to the surgical
      management of AIDS patients in general, the treatment of the increasingly long
      list of surgical complications specific to AIDS patients in particular, and the
      risks of patient-to-surgeon and surgeon-to-patient HIV transmission. Because of
      migration of individuals and populations throughout the world, even surgeons
      practicing in relatively unaffected regions should be familiar with the potential
      surgical implications of AIDS. Ethical considerations arise, as well. Are
      surgeons obliged to operate on HIV-positive or AIDS patients? Some surgeons
      adhere strictly to the Hippocratic Oath, whereas others reserve the right to be
      selective on whom they operate, except in emergencies. Other common ethical
      considerations in the AIDS patient are similar to those arising in the terminal
      cancer case: whether to operate or not; whether to provide advanced support such
      as total parenteral nutrition or hemodialysis. Answers are not simple and require
      close collaboration between the surgeon, the AIDS specialist, and involved
      members of other specialties. Emergency operations become necessary to treat AIDS
      independent disease such as acute cholecystitis and appendicitis or AIDS-related
      life-threatening conditions such as gastrointestinal bleeding, obstruction,
      perforation, or ischemia complicating Kaposi's sarcoma, lymphoma, and
      cytomegalovirus or disseminated nontuberculous mycobacterial infections. Delays
      and errors in diagnosis are frequent. Poor nutritional state with weight loss,
      low serum albumin, and leukocyte count prevails in most patients requiring
      emergency operations and account for a high mortality. By applying solid judgment
      and selecting management appropriately, the surgeon has the ability to prolong
      life and to improve the quality of life for these unfortunate patients, and to do
      so with extremely minimal risk to himself and his team.

PMID- 8875300
TI  - Local antibiotic prophylaxis in surgery.
AB  - The perioperative use of antibiotics is an established and accepted technique for
      the prevention of postoperative infection. Intravenous administration often is
      preferred, and intramuscular administration is possible, although it has certain
      drawbacks. This article examines a variety of other routes of administration for
      delivering antibiotics locally to the surgical site. These techniques merit
      further study in prospectively randomized trials.

PMID- 8875301
TI  - Prevention of fungal infections in hematology patients.
AB  - Endogenous infections such as candidiasis can be minimized by oral fluconazole
      prophylaxis, although oral or intravenous amphotericin, or itraconazole, are
      suitable for certain patients. Exogenous fungal infections most commonly are
      transmitted by the airborne route, but the benefits of high-efficiency
      particulate air-filtered room air probably are diminishing as broad-spectrum
      prophylaxis against Aspergillus species and other fungi improves. However, high
      risk environmental sources such as construction work always must be avoided near
      neutropenic patients. Reactivation of quiescent pulmonary Aspergillus infection
      can be prevented by surgical resection during remission, or by systemic
      amphotericin prophylaxis during subsequent neutropenic episodes.

PMID- 8875302
TI  - Selected aspects of the socioeconomic impact of nosocomial infections: morbidity,
      mortality, cost, and prevention.
AB  - Approximately 2 million nosocomial infections occur annually in the United
      States. These infections result in substantial morbidity, mortality, and cost.
      The excess duration of hospitalization secondary to nosocomial infections has
      been estimated to be 1 to 4 days for urinary tract infections, 7 to 8.2 days for
      surgical site infections, 7 to 21 days for bloodstream infections, and 6.8 to 30
      days for pneumonia. The estimated mortalities associated with nosocomial
      bloodstream infections and pneumonia are 23.8% to 50% and 14.8% to 71% (overall),
      or 16.3% to 35% and 6.8% to 30% (attributable), respectively. The estimated
      average costs of these infections are $558 to $593 for each urinary tract
      infection, $2,734 for each surgical site infection, $3,061 to $40,000 for each
      bloodstream infection, and $4,947 for each pneumonia. Even minimally effective
      infection control programs are cost-effective. In countries with prospective
      payment systems based on diagnosis-related groups, hospitals lose from $583 to
      $4,886 for each nosocomial infection. As administrators focus on cost
      containment, increased support should be given to infection control programs so
      that preventable nosocomial infections and their associated expenditures can be
      averted.

PMID- 8875303
TI  - Epidemiology, diagnosis, and therapy of fungal infections in surgery.
AB  - Over the past decade, the incidence of hospital-acquired bloodstream infections
      caused by Candida strains has risen, while the implicated species have changed.
      Candida tropicalis, Candida parapsilosis, and Candida glabrata all have increased
      in incidence. Data from the Centers for Disease Control and Prevention reveal
      that, between 1980 and 1990, Candida emerged as the sixth most common nosocomial
      pathogen (7.2%) and was the fourth most common pathogen in nosocomial bloodstream
      infections, surpassed only by coagulase-negative staphylococci, Staphylococcus
      aureus, and enterococci. The incidence of candidemia is dramatically higher in
      high-risk critical-care units: 25% of cases occur in surgical intensive-care
      units (ICUs) versus 25% in bone marrow transplantation units, 20% in medical
      ICUs, 20% in general medical wards, and 10% in oncology-hematology units. Burns
      and gastrointestinal surgery predispose to nosocomial candidemia. Independent
      risk factors include prior therapy with multiple antibiotics, isolation of
      Candida from sites other than blood, and prior hemodialysis. Crude mortality
      exceeds 55% and is associated with older age and concomitant renal failure,
      hepatic failure, acute respiratory diseases, or postoperative shock. In addition
      to extreme vigilance for early recognition of Candida sepsis in critically ill
      surgical patients, the high risk for candidemia probably necessitates fungal
      surveillance cultures and initiation of preemptive antifungal therapy in high
      risk surgical patients.

PMID- 8875304
TI  - An unusual host-parasite relationship: the growth hormone-like factor from
      plerocercoids of spirometrid tapeworms.
AB  - Accelerated body growth is associated with experimental infections with the
      plerocercoid stage of the pseudophyllidean tapeworm, Spirometra mansonoides. The
      growth response is due to a protein that is synthesized and released by
      plerocercoids in the host. Plerocercoid growth factor (PGF) is transported by the
      blood, interacts with growth hormone (GH) receptors and mimics many of the
      biological actions of GH. Purification and characterization of PGF reveals that
      the GH-like factor is a 27.5 kDa cysteine proteinase. Sequencing of a cDNA for
      PGF revealed 40-50% homology to mammalian cysteine proteinases, but no homology
      to any GH. The GH-like factor/proteinase is found in abundance in the tegument of
      plerocercoids where the proteinase activity would be most effective in aiding
      tissue invasion, and possibly evasion, of the host's immune response to the
      parasite. The advantage of the GH-like activity is less clear, but it may affect
      the species survival by suppressing specific elements of the host's immune system
      and by improving the probability that the infected host will be eaten by a
      definitive host by increasing morbidity and/or mortality, conditions which are
      associated with long-term exposure to elevated levels of GH and PGF.

PMID- 8875305
TI  - Phylogenetic tree-building.
AB  - Cladistic analysis is an approach to phylogeny reconstruction that groups taxa in
      such a way that those with historically more-recent ancestors form groups nested
      within groups of taxa with more-distant ancestors. This nested set of taxa can be
      represented as a branching diagram or tree (a cladogram), which is an hypothesis
      of the evolutionary history of the taxa. The analysis is performed by searching
      for nested groups of shared derived character states. These shared derived
      character states define monophyletic groups of taxa (clades), which include all
      of the descendants of the most recent common ancestor. If all of the characters
      for a set of taxa are congruent, then reconstructing the phylogenetic tree is
      unproblematic. However, most real data sets contain incongruent characters, and
      consequently a wide range of tree-building methods has been developed. These
      methods differ in a variety of characteristics, and they may produce
      topologically distinct trees for a single data set. None of the currently
      available methods are simultaneously efficient, powerful, consistent and robust,
      and thus there is no single ideal method. However, many of them appear to perform
      well under a wide range of conditions, with the exception of the UPGMA method and
      the Invariants method.

PMID- 8875306
TI  - Leishmania infantum: infection of macrophages in vitro with promastigotes.
AB  - Leishmania infantum promastigotes in axenic culture exhibit limited infectivity
      for mouse peritoneal macrophages (M phi) in vitro using standard culture
      conditions (37 degrees C; 95% air/5% CO2) compared to Leishmania donovani
      promastigotes which induce notable infections. The infectivity of logarithmic
      (log) and stationary (stat) phase promastigotes of L. infantum was enhanced by
      the addition of fresh homologous serum, but no amastigotes were observed after 4
      days. Prolonged infections, including transformation and survival of
      intracellular amastigotes in BALB/c mouse and hamster resident peritoneal M phi
      and M phi cell line J774.G8 were obtained by incubating M phi for 48 h at 26
      degrees C prior to standard culture. Enhanced infectivity was observed in a
      number of L. infantum strains subject to this transient thermal change.

PMID- 8875307
TI  - The major excretory/secretory protease from Lucilia cuprina larvae is also a gut
      digestive protease.
AB  - The larvae of the fly Lucilia cuprina excrete or secrete a chymotrypsia (LCTb)
      onto the skin of sheep to facilitate the establishment of the larval infestation.
      A combination of immunoblotting and RT-PCR approaches has established that this
      protease is also a gut digestive protease. LCTb is synthesized primarily in the
      cardia, a small highly specialized organ located at the anterior end of the
      midgut and by midgut cells. There is also some expression by the hindgut but no
      expression by salivary glands. Excretion of LCTb with waste products or
      regurgitation of the gut contents of the larvae may explain how this protease is
      transferred from the larval gut onto ovine skin. LCTb is first expressed in eggs
      and constitutively expressed throughout each larval instar, but is not expressed
      in pupae or adult flies. It is concluded that LCTb could be involved in the
      establishment of larvae on sheep skin as well as acting as a general gut
      digestive enzyme.

PMID- 8875308
TI  - Photoperiodic response in the soft tick, Ornithodoros turicata.
AB  - The effects of photoperiod on the feeding, development and quiescent behavior of
      the burrow-dwelling soft tick, Ornithodoros turicata (Duges) were investigated.
      Ticks were assigned randomly to either continuous darkness (DD), a short-day
      photoperiod (L:D 10:14), a long-day photoperiod (L:D 14:10) or constant light
      (LL). Ticks reared under constant light succumbed to much higher mortality than
      those reared under the other conditions. However, photoperiod did not induce
      quiescent behavior in O. turicata; the ticks were active and fed regularly
      throughout the study. Also, ticks reared in continuous darkness developed more
      slowly than those reared under short-day or long-day conditions. In contrast, pre
      oviposition period was significantly longer for ticks reared in long-day
      conditions. Egg-hatch success was significantly higher for ticks reared in
      continuous darkness than for those reared under the photoperiods. The stage
      specific effects of photoperiod on O. turicata are adaptive; these ticks very
      likely utilize photoperiod information to predict seasonal conditions.

PMID- 8875309
TI  - Nucleic acid stains as indicators of Giardia muris viability following cyst
      inactivation.
AB  - A reliable viability assay for Giardia is required for the development of
      disinfection process design criteria and pathogen monitoring by water treatment
      utilities. Surveys of single-staining nucleic acid dyes (stain dead parasites
      only), and double-staining vital dye kits from Molecular Probes (stain live and
      dead parasites) were conducted to assess the viability of untreated, heat-killed,
      and chemically inactivated Giardia muris cysts. Nucleic acid staining results
      were compared to those of in vitro excystation and animal infectivity. Nucleic
      acid stain, designated as SYTO-9, was considered the best among the single
      staining dyes for its ability to stain dead cysts brightly and its relatively
      slow decay rate of visible light emission following DNA binding. SYTO-9 staining
      was correlated to animal infectivity. A Live/Dead BacLight was found to be the
      better of 2 double-staining viability kits tested. Logarithmic survival ratios
      based on SYTO-9 and Live/Dead BacLight were compared to excystation and
      infectivity results for G. muris cysts exposed to ozone or free chlorine. The
      results indicate that SYTO-9 and Live/Dead BacLight staining is stable following
      treatment of cysts with chemical disinfectants.

PMID- 8875310
TI  - Studies of Plasmodium falciparum cytoadherence using immortalized human brain
      capillary endothelial cells.
AB  - The cytoadherence of Plasmodium falciparum-infected erythrocytes was studied
      using immortalized human brain capillary endothelial cells. The immortalized
      cells, denoted as BB19, derived from the human brain endothelium, were
      transformed with the E6E7 genes of human papilloma virus and retained their
      endothelial nature, i.e. tubule formation occurred with Matrigel as a substratum
      and the cells stained positive for Factor VIII-related antigen, or
      vonWillebrand's factor. Surface expression of ICAM-1, VCAM, E-selectin, and CD36
      was demonstrated by immunofluorescence staining with monoclonal antibodies to
      these ligands. Exposure to cytokines (TNF, IFN gamma, IL-1 alpha, and IL-6) and
      lipopolysaccharide resulted in an increase in expression of ICAM-1, VCAM, E
      selectin, and CD36. The BB19 cells bound P. falciparum-infected red blood cells
      with both the FCR-3 and the ITO4 strains. Antibodies to CD36 and ICAM-1 partially
      inhibited the binding of the FCR-3 and the ITO4 lines, respectively. These
      findings suggest that BB19 cells may be useful in the analysis of receptor-based
      cytoadherence and sequestration, as well as in the cell biology of microvessel
      formation.

PMID- 8875311
TI  - The likelihood of detecting differences between groups of sheep following
      deliberate infection with Ostertagia circumcincta.
AB  - An examination of variation following deliberate infection with Ostertagia
      circumcincta suggested that even large parasitological differences among groups
      have little chance of being detected unless the number of sheep in each group is
      quite large. Tables that give the probability for various sample sizes are
      presented; these tables should aid the interpretation of previously published
      results and may assist in the design of future experiments.

PMID- 8875312
TI  - A comparison of the ectoparasite assemblage on snapper, Pagrus auratus, from
      different regions in Australia and from New Zealand.
AB  - Different species dominate the ectoparasite assemblage on P. auratus in Australia
      and New Zealand, although the same or similar species are available in both
      countries. The same species of parasite show different patterns of dominance
      among the same age classes in both countries. Diversity tends to decrease with
      increase in age class due to an increase in dominance by 1 species. Cluster
      analysis of per cent similarity data indicate consistent patterns by age class
      within locality as well as age class among locality. Samples taken a decade apart
      in the same or nearby locality show a consistent pattern of dominance, diversity
      and similarity that indicates an overall predictability in the structure of the
      assemblage within a region.

PMID- 8875313
TI  - Acute fulminating babesiosis in hamsters infected with Babesia microti.
AB  - In this study, Babesia microti (ATCC30222) from mice was adapted to golden
      hamsters. The parasite was passaged to immunosuppressed and then adapted to
      normal hamsters. When 30 normal hamsters were inoculated with this strain,
      parasitaemia increased to 74% of erythrocytes by day 7 and 70% of the hamsters
      died. By day 12, parasitaemia extended to 90%, with 97% mortality. Hearts and
      kidneys from infected animals were enlarged. Histopathology revealed acute
      myocarditis, hepatitis, pneumonitis, glomerulonephritis and splenomegaly. Giemsa,
      Acridine Orange and Rhodamine staining of the parasite were compared. Scanning
      electron microscopy of blood from infected hamsters revealed from 1 to 5 intra
      erythrocytic parasites.

PMID- 8875314
TI  - Comparison of 2 centrifugation procedures in the formalin-ethyl acetate stool
      concentration technique for the detection of Cryptosporidium oocysts.
AB  - A comparison between the standard formalin-ethyl acetate (FEA) stool
      concentration procedure (centrifugation at 400 g for 2 min) and a modification
      proposed to increase the recovery of Cryptosporidium oocysts (500 g for 10 min)
      was performed on 73 formalin-preserved stool specimens known to be positive for
      Cryptosporidium. False-negative results were obtained with both methods, but the
      increase in centrifugation time and force resulted in the detection of a higher
      number of oocysts and positive samples. The modified procedure had a sensitivity
      significantly higher than the standard method (99% compared to 86%, P = 0.0045).

PMID- 8875315
TI  - Developmentally regulated expression of a Haemonchus contortus surface antigen.
AB  - All life cycle stages of Haemonchus contortus were screened with antibody
      secreting cell (ASC) probes generated from immune sheep 5 days after a challenge
      infection. An antigen with an approximate molecular weight of 70-90 kDa was found
      to be predominantly expressed in the 3rd-stage larvae, while a molecule with an
      approximate molecular weight of 28-31 kDa was recognised by the ASC-probes in the
      earlier developmental stages. Antisera generated against the purified 70-90 kDa
      molecule and antibodies eluted from the 70-90 kDa region in the 3rd-stage larvae
      were found to react with the 28-31 kDa region in the 2nd-stage larvae. These
      results suggest that the 70-90 kDa antigen, previously identified as a major 3rd
      stage surface antigen, is synthesised as a lower molecular weight molecule in the
      earlier larval stages and assembled into a higher molecular weight complex
      through non-reducible covalent bonds.

PMID- 8875316
TI  - Time course and regional expression of C-FOS and HSP70 in hippocampus and
      piriform cortex following soman-induced seizures.
AB  - The time course of induction of the proto-oncogene c-fos and the inducible heat
      shock hsp70 gene was studied from 5 minutes to 24 hours at both transcriptional
      (c-fos and hsp70 mRNA) and translational levels (C-FOS and HSP72 proteins) in the
      rat hippocampus and piriform cortex (Pir) after soman-induced seizures. Induction
      of c-fos was noticed as early as 5 minutes after seizures onset in all fields of
      hippocampal formation (CA1, CA3, CA4, and dentate gyrus) and in piriform cortex.
      The most intense induction was observed in piriform cortex. A sustained
      activation of c-fos occurred in Pir and in CA1, CA3, and CA4 areas of
      hippocampus. Nevertheless, histological analysis showed rare affected neurons in
      CA4, whereas damage was severe in Pir and in CA1 and CA3 hippocampal subfields.
      Induction of hsp70 mRNA occurred but was delayed in all areas previously
      exhibiting c-fos expression. Nevertheless HSP72 protein was never expressed in
      the structures where injury was high (i.e., CA1 and piriform cortex) and mainly
      occurred in the less damaged structure (i.e., CA4 area of hippocampus). Regional
      expression of glial fibrillary acidic protein mRNA was also studied in order to
      exclude an astroglial origin of the c-fos and hsp70 gene inductions. Our results
      demonstrated that after soman induced-seizures 1) there was no strict correlation
      between time course or intensity of neuronal c-fos induction and subsequent
      neuropathology, and 2) the most lesioned areas did not express HSP72 protein in
      spite of intense mRNA induction, suggesting that transcriptional and
      translational events for hsp70 gene might vary according to the severity of
      seizure insult.

PMID- 8875317
TI  - Mapping the adhesive domains of the myelin Po protein.
AB  - The Po protein holds PNS myelin compact at the intraperiod line by homophilic
      interactions of its single immunoglobulin (Ig)-like domain. Using transfected
      Chinese hamster ovary (CHO) cells expressing Po we can monitor this adhesion in
      vitro and have shown that the cells expressing Po when incubated as a single-cell
      suspension form large aggregates, whereas control-transfected cells do not. To
      precisely map the domains of Po responsible for Po:Po-mediated membrane adhesion,
      the ability of a number of antibodies raised to peptides corresponding to
      segments of the Ig-domain of Po, and the ability of the Po-peptides themselves,
      to inhibit aggregation was assessed. Both antibodies to Po-peptide, SDNGT,
      corresponding to amino acids Po 91-95, and the peptide itself, were able to block
      adhesion completely. Furthermore, within this Po sequence, amino acids Asp 92 and
      Gly 94 are conserved in a large number of V-like Ig-domains. To determine if
      these two amino acids are important for Po-mediated adhesion, the nucleotides
      coding for Asp 92 and Gly 94 were mutated to encode glutamate and alanine,
      respectively. Although the mutated Po reached the surface in transfected CHO
      cells and was glycosylated, the cells did not aggregate. These results suggest
      that the sequence SDNGT in the extracellular domain of Po is important for
      adhesion. In addition, antibodies to a second sequence, Po 74-82, and the peptide
      itself, also partially inhibited Po: Po-mediated adhesion indicating that there
      is more than one adhesive domain on Po-protein.

PMID- 8875318
TI  - Rat oligodendrocytes and astrocytes preferentially express fibroblast growth
      factor receptor-2 and -3 mRNAs.
AB  - Fibroblast growth factors (FGFs) exert various effects on glial cells as well as
      on neurons in the brain. The mRNAs for four FGF receptors (FGFR-1-FGFR-4) are
      expressed in the brain. Although FGFR-1 and -4 mRNAs are preferentially expressed
      in neurons, FGFR-2 and -3 mRNAs are preferentially expressed in glial cells.
      However, the glial cells that express these receptors remained to be identified.
      In this study, we found that oligodendrocytes and astrocytes in the brain
      preferentially expressed FGFR-2 and FGFR-3 mRNAs, respectively. The isoforms of
      immunoglobulin-like domain III (IIIb and IIIc) of the receptors have crucial
      roles in ligand binding. We also determined the isoforms of FGFR-2 and FGFR-3
      expressed in glial cells to be of type IIIc. The expression of FGFR-2 IIIc and
      FGFR-3 IIIc with different ligand specificities might play important roles in the
      various effects of FGFs on oligodendrocytes and astrocytes.

PMID- 8875319
TI  - Induced expression of neurotrophins in transgenic mice overexpressing ornithine
      decarboxylase and overproducing putrescine.
AB  - Transgenic mice overexpressing ornithine decarboxylase (ODC) were recently
      generated (Halmekyto et al.: Biochem Biophys Res Commun 180:262-267, 1991). The
      dramatic ODC overexpression resulted in a very high accumulation of the polyamine
      putrescine in the brain. As elevated polyamine levels in the brain are believed
      to be associated with neuronal damage, we studied whether enhanced putrescine
      accumulation in the brain of these mice affects the expression of neurotrophins
      and their high affinity receptors. Northern blot analysis indicated that mRNA
      levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and
      neurotrophin-3 (NT-3) were significantly elevated about 1.5-fold in the
      hippocampus of ODC transgenic mice as compared with control animals. The levels
      of BDNF, NGF and NT-3 mRNA were also elevated in the kidneys of the transgenic
      mice. In eight other tissues examined there were no significant differences. The
      expression pattern of BDNF mRNA and of trkB and trkC (high affinity receptors for
      BDNF and NT-3 respectively) immunoreactivity in the hippocampal formation did not
      reveal significant differences. The induction of the expression of neurotrophins
      could belong to neuroprotective measures triggered by ODC overexpression.

PMID- 8875320
TI  - Effects of FGF-1 and FGF-2 on GD3 immunoreactive spinal neuroepithelial cells.
AB  - Embryonic central nervous system neuroepithelial cells are a transient population
      of cells that give rise to neuronal and glial progenitors. In the E12-E16
      embryonic rat spinal neural tube we have identified neuroepithelial cells as
      radially oriented cells expressing the GD3 ganglioside as recognized by the
      monoclonal anti-GD3 ganglioside antibodies, R24 and LB1. In vitro,
      neuroepithelial cells, which migrate from the ventral aspect of E12 rat
      lumbosacral neural tube explants, also express GD3 ganglioside immunoreactivity,
      thus permitting their distinction from neural crest cells (NCC) which migrate
      from the dorsal aspect of such explants. Fibroblast growth factor-1 (FGF-1,
      acidic FGF) and FGF-2 (basic FGF) increase the migration of neuroepithelial cells
      and the extent to which they incorporate the thymidine analogue bromodeoxyuridine
      (BrdU). They do not, however, alter the rate at which these migrating
      neuroepithelial cells undergo cell death. Previous observations established the
      actions of FGF-1 and FGF-2 on neuronal and glial cells. The present study
      indicates that these growth factors also influence the motility and proliferation
      of progenitor cells at a developmental stage which precedes their divergence into
      neuronal and glial lineages.

PMID- 8875321
TI  - Expansion of rat oligodendrocyte progenitors into proliferative "oligospheres"
      that retain differentiation potential.
AB  - The limited availability of enriched populations of oligodendroglial progenitors
      has impeded the exploration of the complex spatio-temporal mechanisms which
      dictate the chemical "language" of their biology. We have developed a technique
      to prepare homotypic aggregates of oligodendrocyte progenitors called
      "oligospheres." These were obtained using various approaches (sieving, Percoll
      gradient separation and differential adhesion) to purify oligodendroglial
      progenitors from newborn rat brain. Culturing cells in a mixture of N1 defined
      medium and conditioned medium from the B104 neuronal cell line in the absence of
      adhesive substrate allowed to expand routinely and extensively for several
      months, the oligodendrocyte progenitor population. Under these conditions, the
      resulting population consisted of 98% GD3-positive/GFAP-negative cells. After
      dissociation and plating on polyornithine coated substrates, in the presence of
      low (2%) or high (20%) serum, oligosphere-derived oligodendrocyte progenitors
      were induced to differentiate into GalC-positive oligodendrocytes or GFAP
      positive astrocytes, respectively. When transplanted into the newborn shiverer
      mouse brain, oligospheres were able to provide a focal reservoir of migrating and
      myelinating cells. Oligospheres are thus ideal tools for exploring the biological
      and molecular events of the oligodendrocyte lineage both in vitro and in vivo.

PMID- 8875322
TI  - Axonal growth-related cell surface molecule, neurin-1, involved in neuron-glia
      interaction.
AB  - We purified and characterized a novel axonal growth-related molecule, neurin-1,
      which is anchored to the surface membrane via a phosphatidylinositol (PI)
      linkage. This molecule was detected by a combination of phosphatidylinositol
      specific phospholipase C (PI-PLC) treatment from detergent-soluble mouse brain
      membranes and subsequent Western blot analysis with monoclonal antibody (MAb 2A).
      Neurin-1 is immunologically distinct from other known axonal growth associated
      surface glycoproteins. In immunoblots of embryonic mouse brain membrane, the MAb
      2A recognized a single band at approximately 68 kDa, and showed that neurin-1 is
      mainly associated with fiber-containing regions of developing embryonic mouse
      brain. Expression is immunohistochemically similar to that of cell adhesion
      molecule L1, but in comparison, neurin-1 appears somewhat later. Late in
      embryonic development, neurin-1 appeared to be more stage- and region-specific.
      Its precise localization at the neural cell surface membranes was confirmed by
      immuno-electron microscopy using labeled and cultured live nerve cells. Neurin-1
      was found only on the surface of the axon and growth cone. Neurin-1, otherwise
      termed PI anchor protein, corresponds closely in function to the other PI
      anchored cell adhesion molecules. Anti-neurin-1 antibody (MAb 2A), however,
      perturbs the axonal growth and neural cell migration from the astrocyte feeder
      layer cultures. These results suggest that neurin-1 is one of the important cell
      surface molecules mediated in the neuron and glial cell interaction.

PMID- 8875323
TI  - Effects of Schwann cell transplantation in a contusion model of rat spinal cord
      injury.
AB  - Cultured Schwann cells were transplanted at various delays into a spinal cord
      contusion injury performed at low thoracic level in adult female rats. The
      Schwann cells were purified from the dorsal root ganglia of adult syngeneic
      animals. the transplants were well tolerated, and the transplanted Schwann cells
      invaded the injured spinal cord. As quantified using video image analysis, the
      survival and growth of the transplanted cells were poor when the grafting
      procedure was performed 3-4 days after injury and very good when performed
      immediately or 10 days after injury, in which cases post-traumatic micro- and
      macrocavitation were strongly reduced. In animals grafted immediately after
      injury but not in animals grafted after 10 days, post-traumatic astrogliosis was
      much reduced. The Schwann cells transplanted area was invaded by numerous
      regenerating axons, the vast majority of which were, based on the
      neurotransmitter (CGRP and SP) profile, originating from dorsal root ganglion. No
      regeneration of the corticospinal tract as assessed after anterograde tracing or
      of descending aminergic fibers could be demonstrated.

PMID- 8875324
TI  - Substance P and neurokinin A variations throughout the rat estrous cycle;
      comparison with ovariectomized and male rats: I. Plasma, hypothalamus, anterior
      and posterior pituitary.
AB  - The concentrations of Substance P and Neurokinin A were measured in plasma, and
      the hypothalamo-pituitary complex of 4-day-cycling female, ovariectomized and
      male rats. Estrous cycle-related fluctuations were recorded for these two
      neurokinins. The patterns of plasma concentrations of Substance P and Neurokinin
      A, however, were not similar throughout the rat estrous cycle. The plasma
      concentration of Substance P increased on proestrus at 19.00 hr, while Neurokinin
      A decreased. The plasma concentration of Substance P was positively correlated
      with plasma 17 beta-estradiol levels. In the ovariectomized rat, the absence of
      ovarian steroids led to low levels of plasma Neurokinin A, but the plasma
      concentration of Substance P did not show any change as compared to the estrous
      cycle. In the male rat, a similar observation was made in the presence of a
      testosterone environment. The largest variations in tissue concentration of both
      peptides were observed in the anterior pituitary. Substance P and Neurokinin A
      contents were higher throughout the proestrous day than the 3 other days.
      However, the level fell at 18.00 hr on proestrus, and there were similar falls in
      the hypothalamic contents of Substance P and Neurokinin A at 19.00 hr. In the
      ovariectomized rat, with no gonadal steroids, the hypothalamic and/or anterior
      pituitary levels of Substance P were in the same range as during the estrous
      cycle. However, the hypothalamic levels of Neurokinin A were lower and Neurokinin
      A was undetectable in the anterior pituitary. Substance P and Neurokinin A
      concentrations in the posterior pituitary were stable throughout the estrous
      cycle, with the exception of rises for both peptides on estrous day. Substance P
      levels were much lower in ovariectomized and male rats. These results describe
      large fluctuations in hypothalamic and pituitary Substance P and Neurokinin A
      contents through the estrous cycle in the female rat. They also strongly suggest
      the involvement of gonadal steroids in the differential regulation of Substance P
      and Neurokinin A in the female and male rat.

PMID- 8875325
TI  - Substance P and neurokinin A variations throughout the rat estrous cycle;
      comparison with ovariectomized and male rats: II. Trigeminal nucleus and cervical
      spinal cord.
AB  - Substance P and neurokinin A were assayed in the trigeminal nucleus and cervical
      spinal cord of 4-day cycling female, ovariectomized, and male rats. During the
      estrous cycle, levels were largely stable in the trigeminal nucleus. In
      ovariectomized rats, the levels differed from those on any day of the estrous
      cycle suggesting a weak effect of ovarian steroids. In males, the variations in
      the substance P and neurokinin A contents in the trigeminal nucleus were not
      similar to those in either cyclic or ovariectomized rats. The levels fluctuated
      substantially in the cervical spinal cord. During the first 3 days of the estrous
      cycle, the substance P and neurokinin A contents fell concomitant with the 17
      beta-estradiol surge, suggesting a downregulation of substance P and neurokinin A
      contents by 17 beta-estradiol. Furthermore, on estrus, progesterone seemed to
      inhibit the accumulation of both neurokinins. Testosterone may stimulate
      accumulation of substance P and neurokinin A in the cervical spinal cord, with a
      marked circadian rhythm. These results are in favor of the neurokinin content of
      the spinal cord being regulated by the gonadal steroids. In the trigeminal
      nucleus, only testosterone has an effect.

PMID- 8875326
TI  - Characterization of two distinct populations of detergent resistant membrane
      complexes isolated from chick brain tissues.
AB  - We report the isolation of two distinct populations of detergent resistant
      membrane complexes (DRMCs) from 1-day-old chick brain, utilizing a procedure
      involving Triton X-100 insolubility and sucrose density gradient centrifugation.
      The first population is abundant (1.8% of the total homogenate protein), highly
      enriched for two glycosylphosphatidylinositol (GPI)-anchored proteins (Thy-1 and
      AvGp50), and not enriched for caveolin. The second population is of relatively
      low abundance (0.2% of the total homogenate), contains relatively low levels of
      Thy-1 and AvGp50 enrichment, and is highly enriched in caveolin. Both populations
      of DRMCs are enriched for cholesterol, ganglioside GM1, total kinase and tyrosine
      kinase activities, and c-Src and c-Fyn. However, there are differences in the
      Coomassie-stained protein profiles, phosphoprotein components, tyrosine kinase
      activity, and electron microscopic morphology when the Thy-1 and AvGp50-enriched
      DRMCs are compared to the caveolin-rich DRMCs. In addition, the GPI-enriched
      DRMCs contain CaM kinase type II immunoreactivity, whereas this molecule was
      undectable in the caveolin-rich DRMCs. The isolation of two distinct DRMC
      fractions may be representative of unique plasma membrane signaling domains
      involved in GPI-anchored protein or other receptor-mediated signal transduction
      within the avian nervous system. Further, we have demonstrated for the first time
      that nervous system tissue, in particular the hatch chick cerebellum, contains
      caveolin immunoreactivity.

PMID- 8875327
TI  - Selective toxicity of the general anesthetic propofol for GABAergic neurons in
      rat brain cell cultures.
AB  - The intravenous, short-acting general anesthetic propofol was applied to three
      dimensional (aggregating) cell cultures of fetal rat telencephalon. Both the
      clinically used formulation (Disoprivan, ICI Pharmaceuticals, Cheshire, England)
      and the pure form (2,6-diisopropylphenol) were tested at two different periods of
      brain development: immature brain cell cultures prior to synaptogenesis and at
      the time of intense synapses and myelin formation. At both time periods and for
      clinically relevant concentrations and time of exposure (i.e., concentrations >
      or = 2.0 micrograms/ml for 8 hr), propofol caused a significant decrease of
      glutamic acid decarboxylase activity. This effect persisted after removal of the
      drug, suggesting irreversible structural changes in GABAergic neurons. The gamma
      aminobutyric acid type A (GABAA) blocking agents bicuculline and picrotoxin
      partially attenuated the neurotoxic effect of propofol in cultures treated at the
      more mature phase of development. This protective effect was not observed in the
      immature brain cells. The present data suggest that propofol may cause
      irreversible lesions to GABAergic neurons when given at a critical phase of brain
      development. In contrast, glial cells and myelin appeared resistant even to high
      doses of propofol.

PMID- 8875328
TI  - Characterization of the activation of glutaminase induced by N-methyl-D-aspartate
      and potassium in cerebellar granule cells.
AB  - Chronic stimulation of cerebellar granule cells with N-methyl-D-aspartate (NMDA)
      or KCI induces a specific activation of the enzymes directly involved in
      glutamate neurotransmitter synthesis. Phosphate-activated glutaminase (PAG)
      activity is enhanced in cultured granule neurons incubated with 150 microM NMDA
      or 25 mM KCI. Other enzymes are not affected by this treatment like lactate
      dehydrogenase (LDH) and glutamate dehydrogenase (GLDH), which is also a
      mitochondrial enzyme but not directly involved in neurotransmitter synthesis.
      This effect is dependent on protein synthesis and is induced after 12 hr of NMDA
      or KCI stimulation. Kinetics of PAG activity showed that Km values were
      unaffected, in contrast to Vmax values that were increased approximately 70% and
      215% over control by NMDA and KCI treatment, respectively. For GLDH, we found two
      isoforms that were affected differentially by the experimental conditions.
      Western blot analysis clearly evidenced an increase of approximately 120-180% in
      the amount of PAG in NMDA- and KCI-treated cells, whereas GLDH was not
      significantly modified. These results demonstrate that the NMDA- and KCI-induced
      activation of PAG are not due to the modification of the preexisting enzyme, but
      to an increase in the synthesis of this enzyme. This suggests that NMDA receptor
      stimulation during critical periods of the cerebellar granule cell development
      leads to the activation of gene expression involved in the process of cell
      differentiation.

PMID- 8875329
TI  - Tear EGF concentration following corneal epithelial wound creation.
AB  - The effect of corneal epithelial wound creation on epidermal growth factor (EGF)
      concentration in tears was evaluated in order to better understand the effects of
      EGF on the wound healing process. The tears of New Zealand white rabbits were
      sampled by micropipette one day prior to wounding, immediately prior to the
      creation of a 7.5 mm diameter anterior keratectomy wound, immediately following
      wound creation, and at 1, 2, 3, 7, and 14 days following wounding. A volume of 50
      microL was taken at each sampling time, and all tear samples were assayed for EGF
      by an enzyme linked immunosorbent assay (ELISA). The results demonstrated that
      the concentration of EGF in the tear layer rises dramatically immediately
      following wound creation. The basal measured EGF concentration was approximately
      600 pg/mL; immediately following wound creation, this rose to approximately 1600
      pg/mL. By 1 day following creation of the wound, the concentration of EGF in the
      tears had returned to the basal level. A second, marginally significant increase
      in the tear concentration was noted at 3 days post wounding. The EGF
      concentration in the tears were not significantly different at any other time.
      The measured dramatic rise in EGF concentration in the tears in response to the
      creation of a corneal epithelial wound provides further evidence of the
      importance of tear EGF in the wound healing process. The concentrations in all
      cases were on the order of ng/mL, suggesting that the intercellular
      concentrations in this range result in optimal cell stimulation.

PMID- 8875330
TI  - Ocular mini-tablets for controlled release of timolol: evaluation in rabbits.
AB  - Topical delivery of timolol by inserts or similar controlled-release devices may
      offer distinct advantages over administration by eyedrops. The purpose of this
      investigation was the evaluation in rabbits of ophthalmic inserts (denominated
      mini-tablets, MT) for sustained/controlled release of timolol maleate (TiM). The
      MTs (diameter 3.5 mm, thickness 1.5 mm, average TiM content 0.34 or 0.68 mg) were
      prepared by compressing appropriate mixtures of powders with a standard
      tabletting machine. A thin, rate-controlling membrane was applied over the
      devices by spraying aqueous dispersions of acrylic copolymers. A first series of
      different (uncoated and coated) MTs were tested for release of TiM to the
      lacrimal fluid, using commercial eyedrops (Timoptol 0.5%) as a reference
      standard. Two MTs (one of which was coated) and the same reference solution were
      then selected for an ocular absorption study. Analysis of TiM in the aqueous
      humor indicated that the coated MT was capable of maintaining low and steady
      levels of TiM for at least 19 h, while the other device, identical but uncoated,
      produced a prolonged-pulse effect lasting about 8 h. The apparent mean residence
      time (MRT) of TiM in the aqueous humor was 1.3 h for the reference solution, 3.2
      h for the uncoated MT, and 5.7 h for the coated one. The present preliminary
      results point to the potential validity of coated mini-tablets as simple systems
      for controlled ocular delivery of timolol.

PMID- 8875331
TI  - Transepithelial transport of ascorbic acid by the isolated intact ciliary
      epithelial bilayer of the rabbit eye.
AB  - The purpose of these experiments was to test whether the isolated intact
      epithelial bilayer derived from rabbit ciliary processes transports ascorbic acid
      and to what degree the transport rate in vitro corresponds to the in vivo
      process. The intact ciliary epithelial bilayer of the rabbit eye isolated by
      perfusion was mounted in a particularly constructed Ussing type chamber. Fluxes
      were measured by additions of 14C ascorbate to the hemichamber on either the
      pigmented epithelium (PE) or the nonpigmented epithelium (NPE) side where equal
      concentrations of ascorbate from .02 to 2.0 mM were present. Samples were taken
      at intervals thereafter and counted in a liquid scintillation counter. The
      experiments were done under short circuit conditions to avoid the possible
      influence of fluctuating currents upon the movement of ascorbate. Like the
      earlier iris ciliary body preparations, separation of ascorbate fluxes is also
      done by the isolated intact ciliary epithelial bilayer, and the transport of
      ascorbic acid proceeds by saturation kinetics. The uptake process is accomplished
      entirely by the pigmented epithelium (PE). The Km of the process is 0.97 mM, and
      Vmax was valued at 130 nM/L/hr. Thus, assuming an aqueous flow rate of 2
      microliters/min, the transfer of ascorbic acid across the bilayer occurs at a
      rate required to maintain the ordinary millimolar concentration of ascorbic acid
      in the aqueous humor found in vivo.

PMID- 8875332
TI  - Characterization of the muscarinic receptor subtypes in the bovine corneal
      epithelial cells.
AB  - Muscarinic receptor subtypes in the bovine corneal epithelial cells (BCE) were
      characterized on the basis of their: 1) ligand binding properties, 2) linkage to
      Ca2+ and cAMP cell signaling pathways, and 3) gene transcripts. Receptor
      subtypes, m1 and m2, are indicated by competition experiments using subtype
      selective muscarinic receptor ligands. [3H]N-methylscopolamine ([3H]-MS) binding
      was displaced with IC50s of: 1) 1 microM for the m1 antagonist, pirenzipine; 2)
      51 microM for the competitive m2 antagonist, AFDX-116; 3) 100 microM for the
      competitive m3 antagonist, 4-DAMP. In fural2 loaded BCE, carbachol (0.001 - 100
      microM) increased intracellular Ca2+ concentration ([Ca2+]i), and these responses
      were significantly suppressed if they were preincubated with either atropine (1
      microM) or 1 microM pirenzipine. In the absence of extracellular Ca2+, these
      carbachol-induced increases in [Ca2+]i were depressed. A considerable fall
      occurred with the presence of extracellular Ca2+ and 1 microM verapamil, an L
      type Ca2+ channel blocker. These responses suggest that carbachol increases Ca2+
      influx through an L-type Ca2+ channel in the plasma membrane, in addition to
      mobilizing Ca2+ from an intracellular store. BCE also possessed muscarinic
      receptors which were negatively linked to cAMP production insofar as: 1)
      preincubation with 10 microM carbachol significantly suppressed the increases in
      cAMP accumulation induced by isoproterenol (1 - 25 microM); 2) this blunting
      effect of carbachol on cAMP production was eliminated when the BCE were
      preincubated with either 1 microM AFDX-116, or 100 ng/ml pertussis toxin. The
      results of probing for muscarinic receptor gene expression are partially
      consistent with the ligand binding and functional assays. Reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis revealed the presence of m2 but not
      m1, m3 or m4 gene transcripts. In summary, we obtained pharmacological and
      functional evidence for m1 and m2 receptors in BCE. However, only the m2 gene
      transcript could be detected.

PMID- 8875333
TI  - Natural complex of cytokines is a potent stimulant to posttraumatic regeneration
      in rabbit cornea.
AB  - We elaborated an original technique based on local application of natural complex
      of cytokines (NCC) secreted by autologous peripheral leukocytes. In this study,
      we evaluated NCC influence on the healing of penetrating corneal wounds. NCC was
      derived from supernatants of PHA-stimulated rabbit peripheral leukocytes.
      Biological tests revealed the presence of IL-1, TNF, IL-6, MIF, and LIF in the
      complex. Chinchilla rabbits with standard penetrating corneal wounds received
      daily NCC instillation. The controls were instilled with cultural media 199 with
      antibiotics. At 24 hours, 3, 7, 14 and 30 days post-wounding, the rabbits were
      euthanized. We performed morphometry of corneal cross-sections stained with
      hematoxylin and eosin. In NCC-treated animals, we observed more vigorous
      migration and activation of neutrophils and macrophages followed by augmented
      resorption of fibrin. The later post-injury period (14-30 days) was marked with
      complete healing of the endothelial defect (in the controls, the mass of
      proliferating cells projected into the anterior eye chamber) and mature scar
      tissue with a higher content of fibrous component. NCC-treated eye scars were 1.6
      fold thinner than the controls'. Local application of NCC promotes effective
      healing of posttraumatic cornea. It regulates all stages of regeneration and
      prevents rude scarring.

PMID- 8875334
TI  - Cyclic AMP modulation of active ion transport in the pigmented rabbit
      conjunctiva.
AB  - This study was conducted to determine whether active ion transport in the
      pigmented rabbit conjunctiva was subjected to cyclic AMP modulation. 8-BrcAMP and
      compounds that may affect intracellular cAMP levels were tested for their effects
      on the conjunctival short-circuit current (Isc) following mucosal application.
      Conjunctival Isc was increased by 1 mM 8-BrcAMP, 0.001-20 microM forskolin, 0.01
      2 mM theophylline, 2 microM 1-epinephrine, and 20 microM terbutaline in a Cl(-)
      containing but not in a Cl(-)-free medium. The increase in Isc induced by 1 mM 8
      BrcAMP was reversed by 1 mM N-phenylanthranilic acid, suggesting enhancement of
      Cl- secretion by cAMP. Similarly, the increase in Isc induced by 20 microM
      terbutaline was blunted by 1 microM timolol, suggesting a role for beta 2
      adrenergic modulation of Cl- secretion. Collectively, these results are
      consistent with the notion of cAMP modulation of conjunctival active ion
      transport.

PMID- 8875335
TI  - Antiproliferative activity of a liposomal delivery system of mitoxantrone on
      rabbit subconjunctival fibroblasts in an ex-vivo model.
AB  - Wound healing is the main cause of the failure of filtering surgery in glaucoma.
      We developed a liposomal delivery system of mitoxantrone (MITX), an anthracyclin
      derivative, to allow a single adjuvant administration and to lessen ocular side
      effects of the drug. In order to evaluate the antiproliferative activity of
      liposomal MITX, an ex vivo model consisting in the culture of subconjunctival
      tissue explants from rabbits pretreated with subconjunctival injections of free
      or liposomal MITX was used. We found that both forms of MITX decreased the growth
      rate as well as the explant proliferation surfaces 15 days or 1 month after a
      single administration of the drug in vivo. A morphometric analysis of the cells
      showed that the surface of the fibroblasts exposed to both forms of MITX was from
      10 to 12 times as important as that of the control cells exposed to the empty
      liposomes and to the control buffer. A radioautographic study showed that more
      than 95% of the fibroblasts exposed to both forms of MITX were in the G1 phase of
      the cell cycle, while the control cell population was equally distributed among
      the different phases of the cell cycle.

PMID- 8875336
TI  - The renin-angiotensin system in the rabbit eye.
AB  - We analyzed the components of the renin-angiotensin system (RAS) in ocular
      tissues of normal rabbit eyes and compared the results with those measured in
      rabbit eyes with proliferative vitreoretinopathy and ocular hypertension.
      Proliferative vitreoretinopathy was induced by injection of human platelets into
      the vitreous humor, and ocular hypertension was induced by injection of alpha
      chymotrypsin into the posterior chamber. Angiotensinogen, renin, angiotensin
      converting enzyme (ACE), angiotensin II (Ang II), and Ang II receptors were
      assessed using conventional biochemical techniques. The vascularized tissues of
      normal eyes contained high renin and ACE activities concomitant with low
      concentration of angiotensinogen and Ang II. In general, in the ocular humors,
      the opposite was found. The Ang II receptor density was highest in the uveal
      tract [range 35-190 fmol/mg protein]. The AT1 receptor subtype predominated [>
      80%]. The RAS was only minimally different in the two pathological models except
      that, in ocular hypertension, the renin activity in the uveal tract was reduced [
      50%]. Also, the ratio of AT1 to AT2 receptors changed as compared to control,
      although the total receptor density remained unaltered. In conclusion, we present
      evidence for the presence of a complete local RAS in the rabbit eye, which is
      only marginally affected by the two pathological models studied.

PMID- 8875337
TI  - Actions of imidazolines on bovine ciliary artery.
AB  - A segment of bovine ciliary artery exhibits nonlinear biphasic contractile
      responses to agonists. The maximal responses of oxymetazoline (OMZ) and
      norepinephrine (NE) were 55% and 45%, respectively (KCl = 100%). The relative
      potency comparison based on the ED50 of the first component of the dose-response
      curve was OMZ; 1 > NE; 1/7 > phenylephrine; 1/72. At equipotent doses of NE and
      OMZ, the t1/2 duration of response of the latter agonist was 43 times greater
      than that of the former and, after 3 hrs, responses were 95% reproducible.
      Naphazoline, tetrahydrozoline and para-aminoclonidine did not produce significant
      contraction of the blood vessel but did antagonize the action of the agonists. As
      compared to that of NE, naphazoline was selective in blocking responses of OMZ.
      Phentolamine blocking action of NE was greater than that of OMZ. Nifedipine, 100
      nM, reduced the second component of OMZ response. Although the vascular action of
      NE was blocked by prazosin, the contractile action of OMZ was totally resistant
      to block by 1 microM of prazosin. These results indicate that ciliary artery
      contains a subtype of alpha-adrenoceptors (alpha 11) with low sensitivity to
      prazosin. The tissue also contains a unique OMZ sensitive site or imidazoline
      receptors which exhibit low affinity to alpha-adrenoceptor blockers.

PMID- 8875338
TI  - Tetrandrine inhibits breakdown of blood-aqueous barrier induced by endotoxin and
      interleukin-1 alpha in rats.
AB  - Tetrandrine was shown to significantly inhibit uveitis induced by endotoxin and
      interleukin-1 alpha (IL-1 alpha) in rats. The dose-response curve of IL-1 alpha
      induced uveitis was inhibited in a non-competitive manner. The maximum
      inflammation induced by IL-1 alpha was suppressed to 58.4%, 38.3% and 18.3% of
      the control peak by 5 mg/kg, 10 mg/kg and 20 mg/kg t.i.d. of tetrandrine,
      respectively. The maximum inflammation induced by endotoxin was suppressed to
      56.5% and 38.0% by 5 mg/kg and 10 mg/kg t.i.d. of tetrandrine, respectively. The
      mechanism of tetrandrine's anti-inflammation could involve numerous pathways of
      inflammation processes and multiple inflammatory mediators. The results of this
      study indicate that tetrandrine appears to be a broad spectrum, non-steroidal,
      novel ocular anti-inflammatory agent.

PMID- 8875339
TI  - Inhibitory effects of tetrandrine on intracellular free Ca2+ increase induced by
      glutamate, serotonin and histamine in dissociated retina cells.
AB  - The effects of tetrandrine (Tet) on the elevation of intracellular free Ca2+
      concentration ([Ca2+]i) induced by glutamate, serotonin and histamine in
      dissociated rabbit retina cells were studied. The changes of [Ca2+]i were
      reflected by the fluorescent indicator, Fura-2/AM, employed. In the presence of
      extracellular Ca2+ (1.3 mM), glutamate, serotonin and histamine significantly
      increased the [Ca2+]i in a dose-dependent manner. Glutamate (100 microM),
      serotonin (100 microM) and histamine (200 microM) markedly increased the [Ca2+]i
      of retina cells by 165%, 126% and 58%, respectively. Tet 30 microM significantly
      inhibited the increase of [Ca2+]i induced by glutamate (100 microM), serotonin
      (100 microM) and histamine (200 microM) by 28.0%, 46.8% and 29.0%, respectively.
      A lower concentration (10 microM) of Tet also produced an inhibitory effect on
      the increase of [Ca2+]i but was less effective than the Tet 30 microM. In Ca(2+)
      free Hank's solution, Tet did not produce a significant inhibitory effect on the
      increase of [Ca2+]i caused by serotonin and histamine. These results indicate
      that Tet exercises blocking Ca2+ influx from the extracellular site via NMDA, 5
      HT2 and H1-receptor operated Ca2+ channels and has no obvious effect on the Ca2+
      release from intracellular Ca2+ stores.

PMID- 8875340
TI  - Differential effect of ischemia/reperfusion on pigmented and albino rabbit
      retina.
AB  - The purpose of the study was to compare the retinal sensitivity of pigmented and
      albino rabbits to ischemia/reperfusion-induced electroretinogram (ERG)
      alterations and optic nerve morphological changes. High intraocular pressure
      (HIOP) was induced by applying a suction-cup on the eye and a depression with an
      ophthalmodynamometer. HIOP was maintained for lengths of time (30-75 min). Flash
      ERGs were recorded in dark-adapted animals for ischemia and 2 h reperfusion
      periods. Two weeks later, histological examination of the retinas and optic
      nerves was done. Albino rabbits submitted to 45 min HIOP failed to recover b-wave
      ERG amplitude after 2 h reperfusion, whereas pigmented animals presented a total
      ERG recovery even if ischemia was maintained as long as 75 min. Intravenous
      treatment of albino animals with Lazaroid U74389G led to significant ERG recovery
      at reperfusion. Histological studies show that pigmented rabbit optic nerves
      suffered less damage than the albino ones. These results emphasize the role of
      the pigmentary status of the animals in the retinal sensitivity to ischemia.
      Neuroprotection afforded by the antioxidant U74389G suggests that ocular pigments
      could also protect the retinal functional integrity through a free radical
      scavenging activity.

PMID- 8875341
TI  - Effect of prostaglandins on cultured porcine iris sphincter muscle cells.
AB  - Porcine iris sphincter muscle strips contracted in response to carbachol. The
      tissue contraction was inhibited by prostaglandin (PG) E2 but not by PGF2 alpha.
      In order to investigate the effect of PGs on the iris cells, the porcine
      sphincter muscle cells were grown in culture to a confluence and characterized.
      Using the secondary culture of cells, the effect of PGs on carbachol-induced cell
      contraction was investigated. Both PGE2 and PGF2 alpha at 100 microM blocked cell
      contraction completely. The concentration required to inhibit 50% of the maximum
      contraction in 15 minutes was 10(-6) M for PGE2 and 10(-6)-10(-7) M for PGF2
      alpha. Using PGE2 receptor subtype agonists (EP2 agonist, 11-deoxy-16, 16
      dimethyl PGE2 and EP3 agonist, sulprostone), PGE2 receptor involved in the
      inhibition of carbachol-induced contraction was identified to be of the EP2
      subtype. In support of this characterization, the addition of PGE2 to cultured
      porcine sphincter muscle cells increased intracellular cAMP level. The
      discrepancy in PGF2 alpha effect on carbachol-induced sphincter muscle
      contraction between iris tissue strips and cultured cells suggests that
      nonmuscular cells may be involved in the modulation of the PGF2 alpha effect on
      sphincter muscle cells in vivo.

PMID- 8875342
TI  - Inhibition of cell-induced vitreous contraction by synthetic peptide derived from
      the collagen receptor binding sequence.
AB  - Cell-mediated tractional retinal detachment (TRD) is the end result of various
      intraocular proliferative disorders. Interactions between cells and extracellular
      matrix via cellular surface receptors, integrins, play an important role. Anti
      adhesion therapy has been suggested as a promising way to treat the integrin
      dependent pathological events. We tested three synthetic peptides, Gly-Arg-Gly
      Asp-Ser (GRGDS), derived from the fibronectin receptor binding domain; Try-Ile
      Gly-Ser-Arg (YIGSR), from the laminin receptor binding domain, and Ala-Asp-Gly
      Glu-Ala (ADGEA), from the collagen receptor binding domain, to evaluate their
      inhibitory effect on cell-mediated matrix attachment and vitreous contraction in
      vitro, and on cell-induced TRD in rabbit eyes in vivo. Indirect immunofluorescent
      stain demonstrated both bovine retinal pigment epithelial (RPE) cells and rabbit
      dermal fibroblasts expressed the alpha 2 beta 1, alpha 5 beta 1 and alpha 6 beta
      1 integrins, the collagen, fibronectin, and laminin receptors, respectively.
      GRGDS exhibited a broad spectrum of inhibitory activity on RPE cell attachment to
      extracellular matrices. YIGSR specifically inhibited RPE cell attachment to
      laminin, whereas ADGEA inhibited RPE cell attachment to collagen type I and IV.
      ADGEA inhibited RPE cell-induced vitreous contraction in a dose-dependent manner,
      whereas GRGDS and YIGSR had no effect. ADGEA (1250 micrograms/mL) delayed the
      development of TRD but did not prevent it. ADGEA was nontoxic to cells and
      retina, as demonstrated by cytotoxicity tests and histological examination. The
      synthetic peptide, ADGEA, and its analogs may be potential candidates for the
      treatment of cell-mediated collagenous contraction in the ocular tissues.

PMID- 8875343
TI  - The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic
      anhydrase inhibitor.
AB  - Dorzolamide hydrochloride (S,S-5,6-dihydro-4H-4-ethylamino-6-methylthieno [2,3
      b]thiopyran-2-sulfonamide-7,7-dioxide HCl; MK-507; L-671,152) is a water-soluble,
      potent inhibitor of human carbonic anhydrase isoenzymes II and IV in vitro, the
      respective IC50 values being 0.18 nM and 6.9 nM. In contrast, it was found to be
      a much weaker inhibitor of human carbonic anhydrase isoenzyme I (IC50 value of
      600 nM). The topical administration of one 50 microliters drop of 0.5%, 1% and 2%
      solutions of dorzolamide maximally lowered the intraocular pressure (IOP) of
      glaucomatous monkeys by 22%, 30% and 37%, respectively. Good ocular hypotensive
      activity was also observed in ocular normotensive and hypertensive rabbits. Its
      site of action was within the eye, and the reductions in IOP in both species was
      achieved via decreased aqueous humor inflow. The duration of action of 2%
      dorzolamide was shorter than that of 0.5% timolol in glaucomatous monkeys. The
      IOP lowering activity of timolol in this paradigm was enhanced by the concomitant
      instillation of dorzolamide. Both acutely and repeatedly administered 2%
      dorzolamide did not decrease regional ocular blood flow in the rabbit, and the
      topical instillation of the drug had no adverse effects on the eye of rabbits,
      dogs and monkeys. Dorzolamide has been approved in a number of countries for use
      in patients with ocular hypertension or open-angle glaucoma.

PMID- 8875344
TI  - Effects of Chinese herbal products on mammalian retinal functions.
AB  - Ocular ischemia and inflammation are two major factors which induce retinal
      degeneration. Treatment of these diseases has been difficult, though numerous
      agents have been tried. Natural products could be a good field to venture into
      because various medicinal plants have been used for centuries to treat
      circulation stasis, inflammation, visual disturbances, and eyesight failure.
      Tetramethyl-pyrazine, coumarin, methyl tyramine, rescinnamine, apocynin, and
      hesperetin are some natural products isolated from Chinese herbs for improving
      ocular blood flow, particularly in the choroid and retina. For ocular
      inflammation, at least a dozen natural products are reviewed in this article.
      Among those, matrine, tetrandrine and osthole draw particular attention, because
      they are effective mainly as interleukin-1 blockers, but not as arachidonate
      blockers. As a result, these agents are potent anti-inflammatory agents and are
      even more potent than the prototype corticosteroid, prednisolone. It is hoped
      that all aforementioned agents can be used to treat retinopathies resulting from
      ocular ischemia and/or ocular inflammation. Scoparone, corylifolinin,
      epigallocatechin-3-0-gallate, esculetin, and lespedezaflavanone A are some
      natural products which can improve retinal functions measured with
      electroretinogram's b-wave recovery. Further research should be carried out to
      relate natural products which can improve ocular blood flow and inflammation to
      retinal function and vice versa.

PMID- 8875345
TI  - A population pharmacokinetic model for docetaxel (Taxotere): model building and
      validation.
AB  - A sparse sampling strategy (3 samples per patient, 521 patients) was implemented
      in 22 Phase 2 studies of docetaxel (Taxotere) at the first treatment cycle for a
      prospective population pharmacokinetic evaluation. In addition to the 521 Phase 2
      patients, 26 (data rich) patients from Phase I studies were included in the
      analysis. NONMEM analysis of an index set of 280 patients demonstrated that
      docetaxel clearance (CL) is related to alpha 1-acid glycoprotein (AAG) level,
      hepatic function (HEP), age (AGE), and body surface area (BSA). The index set
      population model prediction of CL was compared to that of a naive predictor (NP)
      using a validation set of 267 patients. Qualitatively, the dependence of CL on
      AAG, AGE, BSA, and HEP seen in the index set population model was supported in
      the validation set. Quantitatively, for the validation set patients overall, the
      performance (bias, precision) of the model was good (7 and 21%, respectively),
      although not better than that of the NP. However, in all the subpopulations with
      decreased CL, the model performed better than the NP; the more the CL differed
      from the population average, the better the performance. For example, in the
      subpopulation of patients with AAG levels > 2.27 g/L (n = 26), bias and precision
      of model predictions were 24 and 32% vs. 53 and 53%, respectively, for the NP.
      The prediction of CL using the model was better (than that of the NP) in 73% of
      the patients. The population model was redetermined using the whole population of
      547 patients and a new covariate, albumin plasma level, was found to be a
      significant predictor in addition to those found previously. In the final model,
      HEP, AAG, and BSA are the main predictors of docetaxel CL.

PMID- 8875346
TI  - Tissue distribution kinetics as determinant of transit time dispersion of drugs
      in organs: application of a stochastic model to the rat hindlimb.
AB  - A stochastic theory of drug transport in a random capillary network with
      permeation across the endothelial barrier is coupled with a model of tissue
      residence time of drugs assuming radial intratissue diffusion. Axial diffusion is
      neglected both in tissue as well as in the radially well-mixed vascular phase.
      The convective transport through the microcirculatory network is characterized by
      an experimentally determined transit time distribution of a nonpermeating
      vascular indicator. This information is used to identify three adjustable model
      parameters characterizing permeation, diffusion, and steady-state distribution
      into tissue. Predictions are made for the influence of distribution volume,
      capillary permeability, and tissue diffusion on transit time distributions. The
      role of convection (through the random capillary network), permeation, and
      diffusion as determinants of the relative dispersion of organ transit times has
      been examined. The relationship to previously proposed models of capillary
      exchange is discussed. Results obtained for lidocaine in the isolated perfused
      hindleg in rats indicate that although the contribution of intratissue diffusion
      to the dispersion process is relatively small in quantitative terms, it has a
      pronounced influence on the shape of the impulse response curve. The theory
      suggests that the rate of diffusion in muscle tissue is about two orders of
      magnitude slower than in water.

PMID- 8875347
TI  - Pulmonary distribution of alfentanil and sufentanil studied with system dynamics
      analysis.
AB  - We applied a system dynamics approach to the study of the pulmonary distribution
      of alfentanil and sufentanil in anesthetized pigs and patients, respectively.
      This method allows estimation of the mean transit time through the lungs and
      calculation of the volume of distribution of alfentanil in the lungs. In the
      first part of the study the pulmonary distribution of alfentanil was studied in
      six anesthetized pigs during three hemodynamic states (control, partial clamping
      of the inferior vena cave, and complete clamping of the right pulmonary artery).
      In the second part of the study the pulmonary distribution of sufentanil was
      studied in 10 patients, scheduled for elective CABG, during and after a constant
      rate infusion of 10 min. Pulmonary passage of the opioids was characterized by
      functions of transit times, derived from the pulmonary arterial and systemic
      arterial concentration curves. Pulmonary distribution volumes were calculated
      from the mean transit time and pulmonary blood flow. Pulmonary distribution
      volume of alfentanil during the control measurement was significantly higher (486
      +/- 88 ml) than during either partial caval clamping (346 +/- 89 ml, p < 0.05) or
      right pulmonary artery clamping (336 +/- 56 ml, p < 0.05). There was no change in
      the extravascular volume of distribution of alfentanil with each hemodynamic
      state. Pulmonary volume of distribution of sufentanil in the patients was 22.6
      (10.9) L. Pulmonary distribution of opioids can be studied using system dynamics
      analysis, both after bolus injection and during and after infusion. This method
      can be used for periods beyond the initial passage of the drug through the lungs.

PMID- 8875348
TI  - Hepatic conjugation/deconjugation cycling pathways. Computer simulations
      examining the effect of Michaelis-Menten parameters, enzyme distribution
      patterns, and a diffusional barrier on metabolite disposition.
AB  - Conjugation/deconjugation cycling plays an important role in the physiologic
      regulation of the concentration of endogenous compounds that form conjugated
      metabolites. Less is known concerning the deconjugation of xenobiotics. The model
      compound p-nitrophenol (pNP) is conjugated to sulfate and glucuronide metabolites
      which can also undergo hydrolysis, via separate enzyme systems, to regenerate
      pNP. In the present investigation, computer simulations were performed using
      literature values for the KM and Vmax for each of the four enzyme systems
      involved in net pNP conjugation. The apparent sulfation rate, apparent
      glucuronidation rate, and the extraction ratio (E) of pNP were each examined (i)
      as a function of pNP concentration, (ii) following alterations in the KM and Vmax
      values for the deconjugation enzymes, (iii) after modulating the enzyme
      distribution patterns along the liver flow path for both the conjugating and
      deconjugating enzymes, and (iv) in the presence of drug metabolite diffusional
      barriers for membrane transport. Results of these simulations demonstrated that
      changes in the KM or Vmax for deglucuronidation produced changes not only in net
      glucuronidation but also in net sulfation. Overall extraction (E) of the parent
      compound was only affected when glucuronidation was an important pathway, i.e.,
      at higher pNP concentrations. Similar results were observed with changes in
      desulfation, with desulfation having the greatest effects at low pNP
      concentrations where sulfation represents the predominant metabolic pathway.
      Changes in the enzyme distribution patterns for the deconjugation pathways showed
      that the greatest influence on net conjugation rates occurred when hydrolase
      enzyme activity was distributed downstream from the respective forward reaction.
      In the presence of a diffusional barrier for metabolite transport (i.e., when the
      diffusional clearance was one tenth of blood flow), net metabolism of parent was
      diminished with E decreasing from 0.74, in the absence of a barrier, to 0.23,
      since the generated metabolite remained, to a great extent, within hepatocytes
      and underwent a more pronounced hydrolysis. In the presence of diffusional
      barriers for uptake of the conjugated metabolites, the lowest drug extraction and
      metabolite formation rates were observed when the distribution of the conjugation
      and deconjugation pathways across the liver were the same. Therefore, the effects
      of deconjugation on hepatic drug removal and metabolite formation are highly
      dependent on the enzymatic parameters of both the forward and reverse reactions,
      the parent drug concentration, the enzyme distribution patterns, and the presence
      of diffusional barriers for metabolite membrane transport. Since a change in the
      deconjugation of one metabolite can influence the net formation of not only
      itself but also other metabolites, and overall drug extraction, evaluation of
      conjugation/deconjugation cycling represents an important consideration in
      pharmacokinetic studies involving physiological-, pathological-, or
      pharmacological-induced alterations in conjugate formation.

PMID- 8875349
TI  - Comparison of some practical sampling strategies for population pharmacokinetic
      studies.
AB  - Using population analysis, sparsely sampled Phase 3 clinical data can be utilized
      to determine the pharmacokinetic characteristics of the target population. Data
      arising from such studies are likely to be constrained to certain sampling
      windows, i.e., the visiting hours at the study clinic. When the sampling window
      is narrow compared to the half-life of the drug, the advantage of taking more
      than one sample is not obvious. Study designs with one or two samples per visit
      have been compared with respect to (i) precision and bias of the population
      parameter estimates, (ii) the ability to identify the underlying pharmacokinetic
      model, and (iii) the estimation of individual parameter values. The first point
      was assessed using simulated data while the latter two were studied using a real
      data set. Results show: (i) Parameter estimates are more biased and imprecise
      when only one sample is taken compared to when two samples are obtained, this is
      true irrespective of the time span between the two samples. (ii) Ability to
      identify a more complex model is increased if two samples are taken.
      Specifically, the variability between occasions can be quantified. (iii) Two
      sample designs are generally better with respect to prediction of individual
      parameter values. Even minor changes to commonly employed study designs, in this
      case the addition of one sample at each study occasion, can improve quality and
      quantity of the information obtained.

PMID- 8875350
TI  - Inadvertent prostatectomy as a complication of cryptorchidectomy.

PMID- 8875351
TI  - Dorsal laminectomy.

PMID- 8875352
TI  - Deep mycotic infections in cats.
AB  - A review of deep mycotic infections assessed incidence, signalment, clinical
      presentation, and outcome in 571 feline cases. Pertinent findings included a
      predisposition in young, male cats for Sporothrix schenckii and Blastomyces
      dermatitidis. There was an increased incidence of feline leukemia virus infection
      in cases with histoplasmosis and of feline panleukopenia virus infection in cases
      with either aspergillosis or mucoralosis. Few other predisposing conditions were
      identified. Cryptococcosis, coccidioidomycosis, and sporotrichosis had better
      prognoses for recovery. Blastomycosis, histoplasmosis, and aspergillosis commonly
      were disseminated infections and were associated with guarded-to-poor prognoses.

PMID- 8875353
TI  - Persistent papillomavirus infection in a cat.
AB  - A seven-year-old, neutered male, crossbred Persian was diagnosed as having
      persistent, cutaneous papillomavirus infection. The skin lesions consisted of
      round, multifocal-to-confluent, raised, black plaques on the neck, thorax,
      shoulders, and forelegs. Papillomavirus virions were demonstrated in negative
      stained, electron microscopic preparations of homogenized skin lesions and within
      the nuclei of cells from the stratum granulosum. Avidin-biotin immunoperoxidase
      stains were positive for papillomavirus in the same cells. The cat was euthanized
      due to a clinical diagnosis o concurrent, severe, chronic pancreatitis.

PMID- 8875354
TI  - Evaluation of a saliva test kit for feline leukemia virus antigen.
AB  - An enzyme-linked immunosorbent assay (ELISA) test kit for the detection of feline
      leukemia virus (FeLV) antigen in saliva was evaluated in 150 cats. Saliva and
      blood samples from all cats were tested for FeLV using the saliva ELISA kit and a
      plasma ELISA kit, respectively. These results were compared with indirect
      immunofluorescent antibody (IFA) testing of blood smears also obtained from each
      cat. The proportion of cats that tested positive were 10%, 7%, and 8% for each
      test, respectively. Using the IFA test as the gold standard, the saliva FeLV test
      had a sensitivity of 91.7% and specificity of 97.1%, while the plasma ELISA test
      had a sensitivity of 91.7% and specificity of 100%.

PMID- 8875355
TI  - The use of a synthetic prostaglandin E1 analog as a gastric protectant against
      aspirin-induced hemorrhage in the dog.
AB  - Misoprostol prevented gastric hemorrhage in dogs, each of which received aspirin
      (35 mg/kg body weight, orally q 8 hrs for 10 days). All dogs receiving aspirin
      alone had gastroscopic and histopathological lesions. No lesions were noted in
      four of five dogs given aspirin plus misoprostol (15 micrograms/kg body weight, q
      8 hrs for five days; then 7.5 micrograms/kg body weight, q 8 hrs for five days).
      Four of 10 dogs receiving 15 micrograms/kg body weight of misoprostol developed
      diarrhea. The misoprostol dose was reduced to 7.5 micrograms/kg body weight, and
      the diarrhea subsided.

PMID- 8875356
TI  - Pleural effusion as a complication of extrahepatic biliary tract rupture in a
      dog.
AB  - Bile pleural effusion associated with traumatic rupture of the extrahepatic
      biliary tract and bile peritonitis in a dog is described. Pleural and abdominal
      fluids were identical cytologically and chemically despite a grossly intact
      diaphragm. Transfer of peritoneal fluid across the diaphragm via lymphatics and
      subsequent leakage into the pleural space is the likely cause of effusion.
      Pleural and abdominal fluid accumulation resolved spontaneously with repeated
      abdominocenteses and supportive care.

PMID- 8875357
TI  - A retrospective study of canine hip dysplasia in 116 military working dogs. Part
      I: Angle measurements and orthopedic foundation for animals (OFA) grading.
AB  - The progression of hip dysplasia was investigated in 116 military working dogs.
      Serial pelvic radiographs were graded for degree of dysplasia and degenerative
      joint disease (DJD). Norberg angles, angles of inclination, and joint space
      widths were measured. There was a significant correlation between the Norberg
      angle and the degree of dysplasia (p less than 0.0001). Angles of inclination and
      joint space width measurements did not demonstrate a correlation to canine hip
      dysplasia. Dysplastic dogs had a significant estimated risk for development of
      DJD compared to normal dogs (p less than 0.0001; odds ratio of 70.2). Dogs with
      normal hip conformation at 24 months of age or older did not develop moderate nor
      severe DJD.

PMID- 8875358
TI  - A retrospective study of canine hip dysplasia in 116 military working dogs. Part
      II: Clinical signs and performance data.
AB  - The progression of hip dysplasia was investigated in 116 military working dogs.
      Medical records were reviewed for any clinical history of hind-limb lameness.
      Pelvic radiographs were studied for evidence and degree of hip dysplasia,
      degenerative joint disease, or both. The number of months each dog worked was
      determined. Each dog's age at termination from service and cause of death (or
      euthanasia) were recorded. The mean months of work for normal and dysplastic dogs
      were evaluated using the Student's t-test. No significant difference was found in
      the total number of months worked between normal and dysplastic dogs (p greater
      than 0.05).

PMID- 8875359
TI  - Obstructive tracheal mass due to an inflammatory polyp in a cat.
AB  - A 13-year-old, male domestic shorthair was presented for a 1.5-year history of
      progressive dyspnea. Multiple intratracheal masses were seen on thoracic
      radiographs and during bronchoscopy. A diagnosis of an inflammatory polyp
      infiltrated with lymphocytes and plasma cells was made on histopathological
      examination of the largest mass following excisional biopsy.

PMID- 8875360
TI  - Treatment of Oslerus osleri infestation in a dog: case report and literature
      review.
AB  - Oslerus osleri (O. osleri), found throughout the world, reportedly is the most
      common respiratory nematode of wild and domestic dogs. Oslerus osleri infestation
      was diagnosed in a 1.5-year-old Scottish terrier presenting with a seven-week
      history of progressive cough. Diagnosis was based upon visualization of
      characteristic lesions on bronchoscopic evaluation and recovery of O. osleri
      larvae from tracheal and bronchoalveolar lavage samples on fecal analyses.
      Therapy was successful using anti-inflammatory doses of prednisone (0.5 mg/kg
      body weight, per os [PO] every other day) and thiabendazole (35 mg/kg body
      weight, PO q 12 hrs for five days; then 70 mg/kg body weight, PO q 12 hrs for 21
      days).

PMID- 8875361
TI  - Ligneous conjunctivitis in four Doberman pinschers.
AB  - Ligneous conjunctivitis (LC) was diagnosed in four unrelated Doberman pinschers.
      Thick, opaque membranes of the palpebral conjunctivae and nictitating membranes
      were present bilaterally. Three dogs had concurrent signs of multisystemic
      disease. A thick, amorphous, eosinophilic, hyaline-like material in the
      substantia propria of the conjunctiva--containing a moderate, mononuclear cell
      infiltrate--was evident on histological examination. A predominance of T
      lymphocytes, few macrophages, and weak positive staining for immunoglobulin G
      (IgG) and immunoglobulin A (IgA) were evident by immunohistochemical staining.
      The clinical and histological appearance of LC in Doberman pinschers and humans
      is similar.

PMID- 8875362
TI  - Ceruminous gland tumors in dogs and cats: a review of 124 cases.
AB  - The histological features of 124 ceruminous gland tumors from canine and feline
      biopsy submissions were reviewed. The tissues, which represented submissions from
      private veterinary practices and a veterinary college, included ceruminous gland
      adenocarcinomas and adenomas as well as a single, mixed ceruminous gland
      adenocarcinoma. A majority of the masses from both dogs and cats were identified
      as malignant processes.

PMID- 8875363
TI  - Spirituality in the chronos of AIDS.

PMID- 8875364
TI  - Radiation treatment of oral epidemic Kaposi's sarcoma lesions: potential adverse
      effects.
AB  - Epidemic Kaposi's sarcoma, which has consistently been the most prevalent
      malignancy in people with HIV disease, frequently presents with lesions in the
      oral cavity. Guidelines for treating oropharyngeal lesions with radiotherapy are
      ubiquitous in the literature. Treatment indications include pain, dysphagia, and
      obstruction. Radiotherapy dosage and fractionation differ from that prescribed
      for non HIV-infected people. Current literature reveals better treatment outcomes
      for people infected with HIV if treatment is managed by practitioners experienced
      in HIV care. This article presents a review of the literature and a case study of
      a HIV-infected patient who experienced severe adverse effects of irradiation.

PMID- 8875365
TI  - Nursing care models increase care quality while reducing costs.
AB  - Unique models of care delivery, such as the Nursing Care Partnership model for
      practice used at the Denver Nursing Project in Human Caring, have demonstrated a
      reduction in inpatient admissions, mean length of stay, and total charges. This
      descriptive study identified and described clients' (N = 75) perceptions of care
      and explored the cost-effectiveness of this model. Findings suggest nursing care
      partnerships play a key role in reducing healthcare costs by providing services
      in a more cost-efficient setting and by having an impact on client utilization of
      services. Savings in potential hospital costs were estimated at $1,590,384 for
      1993.

PMID- 8875366
TI  - Gaining a new perspective on life as a consequence of uncertainty in HIV
      infection.
AB  - HIV infection affects the lives of hundreds of thousands of North Americans. The
      experience of those infected is one of enormous upheaval. An HIV diagnosis can
      disrupt both daily life and the ability to plan for the future. Central to this
      experience is the uncertainty of a disease with vague symptomatology, changing
      medical management, and social stigma. This qualitative study explores the
      experience and consequences of uncertainty in the lives of 10 people with HIV
      infection. In-depth focused interviews were conducted to explore uncertainty
      after HIV diagnosis. Findings reveal that individuals living with HIV infection
      form a new perspective on life, which is maintained through five core
      experiences: surviving the HIV diagnosis, taking care, living in the present,
      seeking support, and appreciating the positive. Each core experience is comprised
      of a number of actions used by the individual to formulate and maintain the new
      perspective on life.

PMID- 8875367
TI  - Saquinavir.

PMID- 8875368
TI  - Drug interactions: how they affect people living with HIV/AIDS.
AB  - Given the diversity and increasing life span of HIV-positive people, medical
      management of the associated complications is becoming more complex. This
      complexity is compounded by the growing number of drugs available to treat people
      with HIV/AIDS. Information regarding the adverse reactions and/or interactions of
      these drugs in combination is limited. The purpose of this paper is to review
      what is currently known about synergistic, antagonistic, and potentially toxic
      interactions. Included is a table containing side effects and interactions among
      drugs commonly used to treat clients with HIV/AIDS.

PMID- 8875369
TI  - Subjective global assessment in HIV-infected patients.
AB  - The Subjective Global Assessment (SGA) tool is utilized by multiple disciplines
      to determine the nutritional status of a patient. In this study, the SGA was
      revised for specific use with patients infected with HIV. The revised SGA was
      used with 36 HIV-infected patients (35 males, 1 female) in a clinic setting for
      assessment of nutritional status. The authors describe the results of each
      section of the SGA (weight changes, dietary intake, gastrointestinal symptoms,
      functional impairment, and physical examination). The most severely malnourished
      HIV-infected patients presented with a higher frequency of weight loss and
      gastrointestinal symptoms, a greater degree of functional impairment and wasting,
      and lower albumin and CD4 lymphocyte values. The revised SGA is useful in
      identifying which patients need referral to a registered dietitian for further
      nutritional intervention, education, and follow-up. Utilization of the SGA
      represents a key opportunity for nurses and dietitians to work collaboratively
      for the benefit of the patient.

PMID- 8875370
TI  - Getting the word out: expanding the association of nurses in AIDS care networking
      potential among nurses in clinical practice.

PMID- 8875371
TI  - Calman cometh.

PMID- 8875373
TI  - Staff grade education and training--a way forward. Review of the impact of The
      Royal College of Physicians' Report on staff grade doctors, with further
      recommendations.

PMID- 8875372
TI  - Clinical genetics services into the 21st century. Summary of a report of the
      Clinical Genetics Committee of the Royal College of Physicians.

PMID- 8875374
TI  - Clinical guidelines for cystic fibrosis care. Summary of guidelines prepared by a
      working group of the Cystic Fibrosis Trust, the British Paediatric Association
      and the British Thoracic Society.

PMID- 8875375
TI  - Valvular heart disease: recommendations for investigation and management. Summary
      of guidelines produced by a working group of the British Cardiac Society and the
      Research Unit of the Royal College of Physicians.
AB  - Despite the decline of rheumatic fever, valvular heart disease remains a common
      and important problem. The investigation and treatment of patients have been
      revolutionised by the widespread availability of echocardiography, which provides
      information about disease aetiology, accurate and non-invasive assessment of
      severity and a means of monitoring progression. These advances have facilitated
      progress in reconstructive valve surgery and the application of balloon
      valvuloplasty. Improved valve prostheses and reduction in peri-operative
      mortality have also broadened the indications for valve replacement surgery. A
      working party convened by the British Cardiac Society and the Royal College of
      Physicians of London have reviewed current practice and provided guidelines,
      summarised in this article, for the investigation and management of adults with
      valvular heart disease in primary care, district general hospitals and tertiary
      referral centres.

PMID- 8875376
TI  - Confidential enquiry into counselling for genetic disorders.

PMID- 8875377
TI  - The development of a clinical skills centre.
AB  - Guidelines produced by the General Medical Council of Great Britain have
      emphasised the importance of the development of the skills and attitudes
      appropriate for a junior doctor. Medical schools are in the process of reforming
      their curricula accordingly. The development of these skills is made increasingly
      difficult by changes such as short admissions to hospital, increased care in the
      community, and reduced resources. This article outlines the development of a
      clinical skills centre as a multidisciplinary unit to improve clinical skills
      teaching with the aid of up-to-date technology and educational practices. By
      sharing our experience we aim to provide a practical guide for the development of
      such units in other medical and nursing colleges.

PMID- 8875378
TI  - Dying from heart disease.
AB  - OBJECTIVES: To describe the symptoms experienced in the last year of life by
      people with heart disease, their relation to quality of life, and informal
      carers' satisfaction with hospital services. METHODS: Interview survey of
      informal carers of 600 patients aged 15 and over, approximately ten months after
      their death from heart disease in 1990 in 20 English health districts. The
      districts, while self-selected, were nationally representative in social
      characteristics and indicators of health service provision and use. RESULTS:
      Pain, dyspnoea and low mood were reported to have been experienced by more than
      half the patients in their last year of life. Anxiety, constipation,
      nausea/vomiting, urinary incontinence and faecal incontinence, although not
      suffered by the majority of patients, also caused much distress. Hospital symptom
      control was reported to be limited: little or no symptom relief was reported for
      35% patients with pain, 31% with constipation, 24% with dyspnoea and 24% with
      nausea/vomiting. Nevertheless, high levels of satisfaction with hospital staff
      were reported. CONCLUSIONS: Patients dying from heart disease experience a wide
      range of symptoms, which are frequently distressing, and often last for more than
      six months. There is room for an improvement in palliative care for patients with
      heart disease in hospital.

PMID- 8875379
TI  - Garlic powder in the treatment of moderate hyperlipidaemia: a controlled trial
      and meta-analysis.
AB  - OBJECTIVE: To determine the effect of 900 mg/day of dried garlic powder
      (standardised to 1.3% allicin) in reducing total cholesterol. DESIGN: Double
      blind, randomised six-month parallel trial. SUBJECTS: 115 individuals with a
      repeat total cholesterol concentration of 6.0-8.5 mmol/l and low-density
      lipoprotein (LDL) cholesterol of 3.5 mmol/l or above after six weeks of dietary
      advice. INTERVENTION: The active treatment group received dried garlic tablets
      (standardised to 1.3% allicin) at a dosage of 300 mg three times daily. The
      control group received a matching placebo. OUTCOME MEASURES: Primary end-point:
      total cholesterol concentration; secondary end-points: concentrations of LDL and
      high-density lipoprotein cholesterol, apolipoproteins (apo) A1 and B, and
      triglycerides. RESULTS: There were no significant differences between the groups
      receiving garlic and placebo in the mean concentrations of serum lipids,
      lipoproteins or apo A1 or B, by analysis either on intention-to-treat or
      treatment received. In a meta-analysis which included the results from this
      trial, garlic was associated with a mean reduction in total cholesterol of -0.65
      mmol/l (95% confidence intervals: -0.53 to -0.76). CONCLUSIONS: In this trial,
      garlic was less effective in reducing total cholesterol than suggested by
      previous meta-analyses. Possible explanations are publication bias,
      overestimation of treatment effects in trials with inadequate concealment of
      treatment allocation, or a type 2 error. We conclude that meta-analyses should be
      interpreted critically and with particular caution if the constituent trials are
      small.

PMID- 8875380
TI  - Use of standardised assessment scales in elderly hip fracture patients.
AB  - Standardised scales recommended by a joint working party from the Royal College
      of Physicians (RCP) and The British Geriatrics Society (BGS) in 1992 for the
      assessment of elderly hospitalised patients were employed in an elderly hip
      fracture population to investigate their feasibility and usefulness in this
      group. Patients were assessed at the time of their fracture and one, six and 12
      months later. An informant was invited to provide information on behalf of
      patients (39%) who were classified as having significant memory and cognitive
      impairment (Abbreviated Mental Test score < 7) or if they had some other
      communication difficulty. Patients and informants found the format and content of
      the scales acceptable as well as the administration time of around one hour.
      Difficulties with the depression (Geriatric Depression Scale) and quality of life
      (Philadelphia Geriatric Center Morale Scale) scales were due to some patients'
      digressions, and the fact that little change was noted in the scores over the one
      year period of follow-up questions their sensitivity. In the cohort of survivors
      31% were classified as being depressed at baseline (score > 5) and this rose to
      36% at one year. Ten per cent of the surviving patients were classed as dependent
      by the Barthel Index at the time of their fracture (score < 12) and this
      increased to 24% at one year. Despite exhibiting a ceiling effect, this scale was
      the most responsive of the scales at all time points. The social checklist
      highlighted important aspects for the management of hip fracture patients.

PMID- 8875381
TI  - The role of cytokines in rheumatoid arthritis. The Croonian Lecture 1995.

PMID- 8875382
TI  - Tuberculosis--out of control? The Mitchell Lecture 1995.

PMID- 8875383
TI  - Tobacco: the Third World War advice from General Sun Tzu. The Lilly Lecture 1996.

PMID- 8875385
TI  - Diagnostic logic and validity for the 'short' case.

PMID- 8875384
TI  - Epithelial development and differentiation: the role of desmosomes. The Watson
      Smith Lecture 1996.

PMID- 8875386
TI  - Science and medicine.

PMID- 8875387
TI  - Thrombotic disorders.
AB  - The causes and consequences of thrombosis are of interest and concern to a wide
      range of clinicians and scientists. Accordingly, the Royal College of Physicians
      joined with the Haemostasis and Thrombosis Task Force of the British Society for
      Haematology to hold a conference on thrombotic disorders in October 1995. The aim
      of the conference was to highlight and discuss recent advances in identifying
      patients at risk of thrombosis and ways of inhibiting the coagulation cascade and
      platelet function.

PMID- 8875388
TI  - The general physician in the 1990s.

PMID- 8875389
TI  - College report on neurological services. Future of general medicine.

PMID- 8875390
TI  - Ward based x-rays.

PMID- 8875392
TI  - Chaos in the case notes a case for prevention, not treatment.

PMID- 8875393
TI  - Elderly patients excluded from resuscitation discussion.

PMID- 8875391
TI  - Inequitable variation.

PMID- 8875394
TI  - Magnetic field gradient system for nuclear magnetic resonance microimaging.
AB  - In this study we present an orthogonal magnetic field gradient system for nuclear
      magnetic resonance (NMR) microimaging applications. The construction details are
      given for a prototype assembly for proton microscopy inside a 50-mm vertical bore
      magnet, which is designed to fit into a commercial 300-MHz NMR probe. This system
      has been used to acquire images of the human spinal cord in vitro. Its
      performance has been evaluated and compared to that predicted by computer
      simulation.

PMID- 8875395
TI  - Breathhold imaging of the upper abdomen using a circular polarized-array coil:
      comparison with standard body coil imaging.
AB  - Current studies emphasize the use of array coils to decrease noise and increase
      the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). We applied T1
      weighted and T2-weighted standard nonbreathhold spin echo (SE) sequences and T1
      weighted FLASH, TurboFLASH, T2-weighted spin-echo time (TSE), and heavily T2
      weighted half Fourier acquisition single-shot TSE (HASTE) sequences during
      breathhold for abdominal imaging in 15 normal volunteers. The breathhold scans
      were performed using both a standard coil and a circular polarized array coil. We
      analyzed the signal intensity (SI), SNR, and CNR of abdominal organs in all
      sequences. SNRs increased in all cases by an overall factor of approximately 3
      due to an 8% increase in overall SIs and a 50% decrease in noise when applying
      the array coil. Although the array-coil FLASH sequence performed at least as well
      as the respective SE sequence, the SNRs of the array-coil TurboFLASH, TSE
      breathhold, and HASTE sequences were generally lower. We conclude that array-coil
      imaging significantly improves fast imaging of the abdomen.

PMID- 8875396
TI  - Effects of partial volume and phase shift between fat and water in gradient-echo
      magnetic resonance-mammography.
AB  - The signal modulations caused by partial volume effect and phase shift between
      fat and water signal in gradient-echo magnetic resonance mammography (GRE MR
      mammography) have been calculated. Based on this, the theoretical sensitivity and
      specificity of GRE MR-mammography has been investigated considering different
      evaluation methods for the gadolinium-diethylenetriamine penta-acetic acid (Gd
      DTPA)-based signal enhancement. The results show that both in- and out-of-phase
      sequences suffer from partial volume effects in voxels that contain both fat and
      water. This can decrease sensitivity to Gd-DTPA uptake in small, fat-embedded
      lesions or in pathology that contains fat interspersed histologically.
      Additionally, out-of-phase sequences can suffer from phase cancellation effects
      that can further decrease their sensitivity to Gd-DTPA uptake. In the worst case
      signal can actually decrease during Gd-DTPA influx. Determination of enhancement
      relative to the baseline value can decrease the specificity of GRE MR-mammography
      in the out-of-phase condition and decrease the sensitivity in the in-phase
      condition. These effects are less pronounced when enhancement is calculated
      relative to fat. These effects need to be understood since Gd-DTPA uptake is the
      prime indicator of malignancy in MR-mammography.

PMID- 8875397
TI  - Knee extension dynamometer: a new device for dynamic isokinetic magnetic
      resonance spectroscopy experiments.
AB  - In the present study we introduce a new device for exercise magnetic resonance
      spectroscopy (MRS). It operates in a standard whole-body scanner. Mechanical
      exertion unit allows maximal 10 degrees to 15 degrees short-arc knee extensions.
      The device operates hydraulically and is based on isokinetic movement. The force
      and work conducted are automatically controlled by the electronic control and
      computer unit. A small surface coil placed on the vastus medialis muscle allows
      the collection of spectra without interfering spectra from nearby resting
      muscles. The force used for the extensions can be followed simultaneously as a
      curve on the screen in the operator's room and the data is transferred to a
      personal computer for later analysis. Total work and fatigue percentage are also
      calculated by the device. It also allows the use of different isokinetic exercise
      protocols. The measurements of force proved reliable in repeat measurements using
      an isokinetic test device as a control. This device has been used clinically for
      over a year, is easy to operate, and offers reliable measurements. It is well
      suited to trials where muscle energy states versus time are followed since it
      allows noninvasive simultaneous quantification of muscle performance and
      collecting MRS spectra at rest, during exercise, and in the recovery phase.

PMID- 8875398
TI  - Left ventricular radial tagging acquisition using gradient-recalled-echo
      techniques: sequence optimization.
AB  - Myocardial tagging with magnetic resonance (MR) imaging offers unique
      possibilities for noninvasive left ventricular (LV) strain analysis. True three
      dimensional strain analysis can be achieved with tags implemented in cardiac
      short axis and long axis images. Spin-echo (SE) techniques have been used for
      these studies. However, this approach is time-consuming: images at different
      phases of the cardiac cycle have to be obtained in successive measurements and
      hence the total number of measurements equals the number of time frames.
      Moreover, the images are often degraded by flow and motion artifacts. The purpose
      of this study was to optimize a faster and more robust MR tagging sequence for
      use on a clinical whole-body 1 T MR system with optimal persistence of the tags
      during the entire cardiac cycle. The tagging pulses were implemented in gradient
      recalled-echo (GRE) sequences and compared to SE-based acquisitions. The effects
      of the use of flow-compensating gradients, the excitation angles, and the angles
      of the saturation pulses have been studied with MR signal simulations and in
      comparative measurements in volunteers. GRE acquisitions with flow-compensating
      gradients are robust techniques for myocardial tagging acquisitions. Use of
      optimized flip angles and saturation pulses can significantly improve delineation
      of the tag and can be used up to at least 700 ms after the R-wave. Therefore, LV
      tagging with GRE acquisitions using optimized MR parameters is a robust and
      promising technique.

PMID- 8875399
TI  - Magnetization transfer of pure DNA and purified sperm nuclei.
AB  - Magnetization transfer (MT) imaging provides a novel opportunity to characterize
      interactions between tissue water and macromolecules. Although several in vitro
      investigations have shown that proteins and lipids are important determinants of
      MT, the contribution of DNA is still unknown. This study was designed to
      determine whether DNA and cell nuclear material exhibit MT. We measured the
      magnetization transfer effect of pure DNA strands and purified bovine sperm head
      nuclei. Although no transfer of magnetization could be detected in samples of
      pure DNA strands, the sperm head nuclei exhibited a strong MT effect that
      increased with increasing solid content of the samples. Since the purified bovine
      sperm head samples consist of large nuclei with only minor traces of perinuclear
      matrix, the measured MT effect arises from the chromatin of the nuclei. The DNA
      fills 90% of the nuclear volume and it is extremely tightly packed as chromatin
      fibers by nucleoproteins. We hypothesize that the numerous intra- and
      intermolecular disulfide bonds that stabilize the chromatin fibers restrict the
      movement of the surface water binding sites of both DNA and protamines and thus
      facilitate the transfer of magnetization. Therefore, the results indicate that
      the amount of nuclear material may positively contribute to MT in tissues.

PMID- 8875401
TI  - Quantitation of automated single-voxel proton MRS using cerebral water as an
      internal reference.
AB  - Data from a previously published, multi-site trial (P.G. Webb, N. Sailasuta, S.J.
      Kohler, T. Raidy, R.A. Moats, R.E. Hurd. Automated single-voxel proton MRS:
      technical development and multisite verification. Magn. Reson. Med. 31, 365-373
      (1994)) of a fully automatic, single-voxel, proton spectroscopy package
      (PROBE/SV, GE Medical Systems) was re-analyzed in terms of absolute metabolite
      concentrations using the cerebral water signal as an internal reference. In 100
      spectra from parietal white matter in normal volunteers ranging in age from 22 to
      34 years at eight sites, overall concentrations of choline (Cho) creatine (Cr),
      and N-acetyl-aspartate (NAA) resonances were found to be 2.00 +/- 0.50, 8.43 +/-
      1.28, and 12.55 +/- 1.76 mumol/g wet weight, respectively. These values are in
      good general agreement with previously published values from quantitative, single
      voxel studies. Metabolite concentrations for NAA, Cr, and Cho across all sites
      had standard deviations of 14.1%, 14.9%, and 25.1%, respectively. Quantitation of
      PROBE data sets is routinely possible by using the cerebral water signal as an
      internal reference.

PMID- 8875400
TI  - Proton chemical shift imaging, metabolic maps, and single voxel spectroscopy of
      glial brain tumors.
AB  - Seventeen patients with presumed glial brain tumors were examined with proton
      chemical shift imaging and single voxel spectroscopy that used different echo
      times. Metabolite resonances were evaluated by metabolic ratios and absolutely by
      correcting for coil load and comparison to phantom measurements. Metabolic images
      were created to visualize the metabolic changes. All patients showed spectra that
      were different from those measured in healthy control subjects. Spectral changes
      were also present in normal-appearing matter (NAM) that was distant from lesions.
      The resonance at 3.55 ppm which is usually assigned to both myo-inositol and
      glycine, was the only one to allow a discrimination between healthy volunteers,
      astrocytoma grade II, and glioblastoma multiforme (GBM) (p < 0.02). From the
      different echo times used we conclude that an increase in this resonance has to
      be assigned to glycine rather than myo-inositol. This resonance might be used to
      grade human gliomas more reliably. Total creatine (Cr) decreased more drastically
      with malignancy than N-acetylated metabolites (NA). This led to a higher NA/Cr
      ratio in GBM compared to astrocytoma grade II. NA/Cr was thus pseudonormal in GBM
      due to a change in both nominator and denominator. This study reveals the
      importance of comparing magnetic resonance spectroscopy data of lesions to
      spectra measured in identical localizations in healthy control subjects instead
      of NAM and the importance of quantifying single metabolic peaks instead of
      creating metabolic ratios in clinical magnetic resonance spectroscopy.

PMID- 8875403
TI  - Time-resolved contrast-enhanced 3D MR angiography.
AB  - An MR angiographic technique, referred to as 3D TRICKS (3D time-resolved imaging
      of contrast kinetics) has been developed. This technique combines and extends to
      3D imaging several previously published elements. These elements include an
      increased sampling rate for lower spatial frequencies, temporal interpolation of
      k-space views, and zero-filling in the slice-encoding dimension. When
      appropriately combined, these elements permit reconstruction of a series of 3D
      image sets having an effective temporal frame rate of one volume every 2-6 s.
      Acquiring a temporal series of images offers advantages over the current contrast
      enhanced 3D MRA techniques in that it I) increases the likelihood that an
      arterial-only 3D image set will be obtained. II) permits the passage of the
      contrast agent to be observed, and III) allows temporal-processing techniques to
      be applied to yield additional information, or improve image quality.

PMID- 8875402
TI  - Determinants of tissue delivery for 129Xe magnetic resonance in humans.
AB  - Magnetic resonance imaging using laser-polarized 129Xe is a new technique first
      demonstrated by Albert et. al. (Nature 370, 1994) who obtained a 129Xe image of
      an excised mouse lung. This paper describes the factors influencing the
      accumulation of inhaled, polarized 129Xe in human tissue. The resulting model
      predicts the 129Xe magnetization in different tissues as a function of the time
      from the start of inhalation, the tissue perfusion rate and partition coefficient
      for xenon, and the relevant T1 decay times. The relaxation times of 129Xe in
      biological tissues are not yet known precisely. Substitution of estimated values
      for these parameters results in an expected signal-to-noise ratio (SNR) from
      polarized 129Xe MR in the brain of approximately 2% of the equivalent SNR from
      proton MR.

PMID- 8875404
TI  - Quantification of citrate concentration in the prostate by proton magnetic
      resonance spectroscopy: zonal and age-related differences.
AB  - A commercial phased-array multicoil was used to acquire water-suppressed
      localized proton spectra of the two major anatomical regions of the prostate. The
      signal-to-noise ratio and spectral resolution allowed identification of peaks
      from choline and creatine, as well as a major peak from citrate. Quantification
      of the citrate peak using experimentally determined relaxation parameters with
      tissue water as an internal concentration reference revealed a marked variability
      between different volunteers. Nevertheless, in each case, the citrate
      concentration was up to fourfold greater in the peripheral zone than in the
      central gland. Furthermore, the difference in citrate concentration between these
      two regions was positively correlated with the subjects age. The results indicate
      a consistent difference in cellular function between the major anatomical regions
      within the prostate and may have important consequences for the application of
      magnetic resonance spectroscopy to the diagnosis of prostatic pathology.

PMID- 8875405
TI  - A computational strategy for the deconvolution of NMR spectra with multiplet
      structures and constraints: analysis of overlapping 13C-2H multiplets of 13C
      enriched metabolites from cell suspensions incubated in deuterated media.
AB  - A computational strategy for the deconvolution of complex spectra involving
      scalar multiplet patterns is presented. This approach fits spectra that can be
      composed of single resonances as well as scalar coupling multiplets for which
      resonance frequencies, intensities, and lineshape parameters can be optimized.
      For multiplets, the coupling constant also is optimized. Any external information
      about the optimizable parameters can be taken into account as external
      constraints. A lineshape described by absorptive and dispersive Lorentzian and
      Gaussian contributions and the baseline with up to 40 Fourier and polynomial
      terms can likewise be optimized. The effectiveness of the procedure is assessed
      on the basis of computer simulated deconvolutions of a composite of 1J(13C-2H)
      multiplets arising from a mixture of all possible 13C-2H isotopomers of
      deuterated L-[3-13C]lactate generated from cell preparations incubated with D-[1
      13C]glucose in D2O, which was analyzed previously with a manual deconvolution
      procedure (R. Willem, M. Biesemans, F. Kayser, W. J. Malaisse, Magn, Reson. Med.
      31, 259-267 (1994)). The use of constraints is shown to lead to an improvement in
      the results. The fitting strategies and the importance of the baseline as an
      origin of bias are discussed.

PMID- 8875406
TI  - An evaluation of the effects of susceptibility changes on the water chemical
      shift method of temperature measurement in human peripheral muscle.
AB  - Divergencies between chemical shift measurements of temperature and directly
      measured values using optical sensors have been studied in vivo in human
      peripheral muscle with the assistance of a variety of experimental and
      theoretical techniques. These include the modelling of both thermal and
      susceptibility changes using two- and three-dimensional finite element methods,
      as well as the use of multi-wavelength near-infrared observations. The conclusion
      of these studies is that a simple temperature calibration is not accessible, with
      results affected by the complex response of the tissue itself.

PMID- 8875407
TI  - A method to improve the B0 homogeneity of the heart in vivo.
AB  - A homogeneous static (B0) magnetic field is required for many NMR experiments
      such as echo planar imaging, localized spectroscopy, and spiral scan imaging.
      Although semi-automated techniques have been described to improve the B0 field
      homogeneity, none has been applied to the in vivo heart. The acquisition of
      cardiac field maps is complicated by motion, blood flow, and chemical shift
      artifact from epicardial fat. To overcome these problems, an ungated three
      dimensional (3D) chemical shift image (CSI) was collected to generate a time and
      motion-averaged B0 field map. B0 heterogeneity in the heart was minimized by
      using a previous algorithm that solves for the optimal shim coil currents for an
      input field map, using up to third-order current-bounded shims (1). The method
      improved the B0 homogenelty of the heart in all 11 normal volunteers studied.
      After application of the algorithm to the unshimmed cardiac field maps, the
      standard deviation of proton frequency decreased by 43%, the magnitude 1H
      spectral linewidth decreased by 24%, and the peak-peak gradient decreased by 35%.
      Simulations of the high-order (second- and third-order) shims in B0 field
      correction of the heart show that high order shims are important, resulting for
      nearly half of the improvement in homogeneity for several subjects. The T2* of
      the left ventricular anterior wall before and after field correction was
      determined at 4.0 Tesis. Finally, results show that cardiac shimming is of
      benefit in cardiac 31P NMR spectroscopy and cardiac echo planar imaging.

PMID- 8875408
TI  - Improved centric phase encoding orders for three-dimensional magnetization
      prepared MR angiography.
AB  - New centric phase encoding orders are introduced for transient state three
      dimensional MR imaging. Unlike previous centric orders, these variants are not
      fixed with respect to differences in the relative y and z fields of view, but are
      tailored to account for the, differential degrees of gradient dephasing in the Ky
      and Kz phase encoding directions and thus maintain the highest weighting for the
      most central k-space values. The new centric orders are compared with previous
      methods in both simulation and experimental magnetization-prepared MR angiography
      of the carotid and renal arteries. In comparison with other tested centric
      orders, the new methods provided better retention of true vessel shape caused by
      isotropic blurring across the phase encoding plane. In addition, the new methods
      provided increased contrast, with the degree of improvement over previous methods
      depending on vessel orientation, size, and degree of inflow.

PMID- 8875409
TI  - Apparent diffusion coefficients in benign and secondary progressive multiple
      sclerosis by nuclear magnetic resonance.
AB  - The diffusion characteristics of water in brain white matter were studied in
      patients with benign and secondary progressive multiple sclerosis (MS), and also
      in normal controls. In the MS patients, both lesions and normal-appearing white
      matter (NAWM) were examined to assess whether pathological differences might be
      evident from the diffusion behavior. A volume-selective technique was used to
      reduce data acquisition time and improve the reliability and precision of the
      measurements. This also allowed the time-dependence of apparent diffusion
      coefficients to be assessed. While lesions from both patient groups showed an
      elevated diffusion coefficient, no differences between the two groups were found.
      In addition, NAWM was elevated for both patient groups compared with the control
      group, although this was only statistically significant for patients with a
      benign disease course. The degree of elevation of the diffusion coefficient
      within the individual lesions measured was not related to the disability of the
      patient. Pathological differences between lesions in patients with different
      disease courses, if they exist, have not been detected in this study of brain
      water diffusion.

PMID- 8875410
TI  - Design of adiabatic selective pulses using optimal control theory.
AB  - Optimal control theory has been applied in the past for the design of RF pulses
      for selective excitation. This was the outcome of having established the
      controllability of the MR spin system for the selective excitation problem.
      "Minimum distance" was the main formulation used for the solution. Because of
      their robust behavior in the presence of inhomogeneous RF fields, adiabatic
      pulses play an important role in spin inversion and excitation. In this study, we
      present a method for incorporating adiabaticity into the optimal control problem
      by enhancing the cost functional with an appropriate term. Two different types of
      adiabatic terms are proposed. Furthermore, two methods are used to solve the
      optimal control problem, namely the Hamiltonian approach and the solution by
      mathematical programming. Design examples include both a frequency selective
      pulse for performing fat suppression by inversion and a regular inversion pulse.
      It is shown that, in the course of optimization, the pulse designer can trade-off
      slice resolution against pulse adiabaticity.

PMID- 8875411
TI  - Recordings of eye movements for stimulus control during fMRI by means of electro
      oculographic methods.
AB  - A method for monitoring eye movements in humans during functional MRI is
      presented. It is based on the acquisition of electro-oculographic (EOG) signals
      near one eye. EOG potentials were amplified and converted into an optical signal
      just outside the head coil. An optical fiber was used for signal transmission
      from inside the magnet bore to the control room. The EOG sensor was tested during
      EPI sequences at 1.5 Tesla without contamination of the MR signal. Some flow
      related artifacts on the EOG were observed inside the magnet, but no additional
      interactions from the MR sequence. An analysis of the latency, direction, and
      amplitude of the saccadic eye movements was possible.

PMID- 8875412
TI  - Contribution of Sinerem used as blood-pool contrast agent: detection of cerebral
      blood volume changes during apnea in the rabbit.
AB  - The authors suggest that ultra-small paramagnetic iron oxide (USPIO) particles
      used as blood pool contrast agents may increase the sensitivity of midfield MRI
      (i.e., less than 1.5 Tesla) to physiological variations in cerebral blood volume.
      This hypothesis was tested on a rabbit model of apnea which increases pCO2 and
      cerebral blood volume. Using Sinerern as the USPIO at a blood concentration of 60
      mumol Iron/kg body weight, an 8% T2*-weighted signal decrease could be observed
      at 1.0 T with 25-33% increase in pCO2. Comparatively, in the absence of USPIO,
      T2*-weighted signal dropped only 4% during apnea and after mild hyperoxygenation
      beforehand, due to increased deoxyhemoglobin content. These preliminary data
      suggest that USPIOs could play an important role in functional MRI at midfield
      strength, by sensitizing the signal to cerebral blood volume changes.

PMID- 8875413
TI  - Influence of membrane lipid packing on T2-weighted magnetic resonance images:
      study of relaxation parameters in model membrane systems.
AB  - The detailed mechanisms leading to soft tissue contrast in MRI are not known. To
      explore the physical basis for this phenomena, the effect of acyl chain packing
      of phospholipid model membranes on water proton relaxation were investigated at
      20 MHz at 40 degrees C. Three variables affecting lipid packing were examined:
      chain composition, toluene concentration, and pH/ionic strength. It is
      demonstrated that the T2 of water protons is strongly influenced by changes in
      lipid packing, while T1 is generally insensitive to these variables. It is also
      shown that small changes in water content (7 wt%) altered both T1 and T2 in all
      systems studied. The results suggest that the physical properties of biological
      membranes in tissues are an important factor in determining T2.

PMID- 8875414
TI  - A comparison of phase encoding ordering schemes in T2-weighted GRASE imaging.
AB  - Gradient and spin echo (GRASE) imaging is an echo train imaging sequence that
      combines gradient and RF refocusing. This combination introduces phase
      modulations into the echo train. If the phase encoding order is linear with echo
      time, these modulations cause severe ghosting artifacts. Changing the order of
      phase encoding can greatly reduce these artifacts. Several phase encoding orders
      for T2-weighted sequences are compared in this paper, linear, partially
      randomized, standard GRASE ordering, and k-banded (kb) GRASE ordering. Different
      possible implementations of GRASE and kbGRASE are also considered. Computer
      simulation is used to compare resolution and artifact levels. Phantom and
      volunteer images are presented. The linear order is most sensitive to ghosting
      artifacts associated with chemical shift, susceptibility differences and static
      field inhomogeneities. The standard GRASE order is least sensitive to these but
      most vulnerable to artifacts associated with short T2 signals, kb-GRASE is a good
      intermediate between linear and standard GRASE and generally shows the lowest
      artifact levels. The partially randomized order gives the most diffuse artifacts.
      Computer simulations show that spatial resolution and contrast with all phase
      encoding orders are similar.

PMID- 8875415
TI  - Real-time adaptive motion correction in functional MRI.
AB  - Functional magnetic resonance imaging (fMRI) of the brain is often degraded by
      bulk head motion. Algorithms that address this by retrospective re-registration
      of images in an fMRI time series are all fundamentally limited by any motion that
      occurs through-plane. Here, a technique is described that can account for such
      motion by prospective correction in real time. A navigator echo is used before
      every image acquisition to detect superior/inferior displacements of the head.
      The displacement information is then used to adjust the plane of excitation of
      the ensuing single-shot echo-planar fMRI axial image. These correction updates
      can be completed in 100 mm with motion sensitivity at least as small as 0.5 mm.
      The efficacy of this method is documented in phantom and human studies.

PMID- 8875416
TI  - 5-Fluorouracil metabolite patterns in viable and necrotic tumor areas of murine
      colon carcinoma determined by 19F NMR spectroscopy.
AB  - High-resolution 19F NMR spectroscopy at 9.4 T was used to study the difference in
      the metabolite pattern of 5-fluorouracil (5-FU) between viable and necrotic
      tissues of C38 murine colon tumors grown in C57BI/6 mice. Studies were performed
      on perchloric acid extracts of these tumor fractions after 5-FU treatment. The
      19F nuclear magnetic resonance spectra exhibited resonances representing 5-FU,
      the catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta
      alanine, as well as several fluoronucleotide anabolites. The absolute
      concentrations of anabolites and catabolites and the anabolite-to-catabolite
      ratio were significantly lower in the necrotic fraction than in the viable tumor
      fraction 50 min after administration of 5-FU, whereas the absolute concentration
      of 5-FU was the same. Therefore, in 5-FU metabolism studies with NMR
      spectroscopy, it is important to consider the necrotic contribution to the tumor
      volume.

PMID- 8875417
TI  - Oxidation of acetate in rabbit skeletal muscle: detection by 13C NMR spectroscopy
      in vivo.
AB  - The results of a proton-decoupled and Overhauser-enhanced 13C NMR study of
      acetate metabolism in skeletal muscle are reported. [2-13C]Acetate was infused
      intravenously over 2 h into anesthetized rabbits, and skeletal muscle in the
      lateral thigh was monitored by 13C NMR spectroscopy at 4.7 T. Stable 13C
      enrichment in carbons 2, 3, and 4 of glutamate was observed at the end of the
      infusion, and the half-time for enrichment was 17 min for glutamate C4 and 50 min
      for glutamate C2 and C3. The contribution of exogenous acetate to acetylcoenzyme
      A was nearly equal in skeletal muscle and heart in vivo (83-87%, measured in
      tissue extracts), comparable with earlier perfused heart studies in which acetate
      was the sole available substrate. Although relative flux through the combined
      anaplerotic pathways (relative to citric acid cycle flux) was higher in quiescent
      skeletal muscle (28%) compared with hearts (3%) from the same animals, actual
      anaplerotic flux was estimated to be substantially higher in heart than in
      skeletal muscle after correcting for differences in citric acid cycle flux in the
      two tissues.

PMID- 8875418
TI  - A technique for detecting GABA in the human brain with PRESS localization and
      optimized refocusing spectral editing radiofrequency pulses.
AB  - A proton magnetic resonance spectral editing technique is presented that uses
      PRESS excitation to achieve spatially localized measurements of brain gamma
      aminobutyric acid (GABA). The homonuclear difference spectroscopy technique
      employs a frequency selective inversion pulse to suppress the creatine resonance
      at 3.0 ppm. The timing of this pulse is optimized to maximize the suppression of
      creatine by minimizing the effect of the editing pulse on the 3.0 ppm resonances.
      The PRESS excitation achieves three dimensional spatial localization in a single
      acquisition making it less sensitive to patient motion than multiple acquisition
      techniques. The performance and utility of this technique were evaluated by
      phantom experiments and by in vivo measurements of brain GABA concentration in 10
      normal subjects.

PMID- 8875419
TI  - Elimination of artifacts in short echo time H MR spectroscopy of the frontal
      lobe.
AB  - Localized 1H spectra from the frontal part of the human brain are often distorted
      by "ghost" artifacts, especially with short echo time PRESS sequences. These
      artifacts are caused by insufficient dephasing of unwanted coherences involving
      magnetization in the sinuses and the mouth. Because the various unwanted
      coherences of a PRESS sequence are dephased differently, the order of the slice
      gradients has a pronounced effect on the spectral quality. For frontal voxels,
      the last slice gradient has to be applied in the axial direction. With this slice
      order, the major metabolites can be quantified with an interindividual
      variability of about 10%.

PMID- 8875420
TI  - Comparison of k-space sampling schemes for multidimensional MR spectroscopic
      imaging.
AB  - For clinical 31P MR spectroscopic imaging (MRSI) studies, where signal averaging
      is necessary, some improvement of sensitivity and spatial response function may
      be achieved by acquiring data over a spherical k-space volume and varying the
      number of averages acquired in proportion to the desired spatial filter. Eight
      different k-space sampling schemes are compared through simulations that provide
      graphs of the spatial response functions (SRF), and tabulations of voxel volumes,
      relative signal-to-noise ratios (SNR), and relative data collection efficiencies
      (SNR per unit volume over the same time). All schemes were based on practical
      experiments, each of which could be implemented in the same length of time. The
      results show that in comparison with cubic k-space sampling with the same number
      of signal averages at each point, spherical and acquisition-weighted k-space
      sampling can be used to achieve reduced Gibbs ringing along the principal axes
      directions, and thus reduced contamination from adjacent tissue in these
      directions, without degradation of voxel volume or SNR.

PMID- 8875421
TI  - Phosphorus nuclear magnetic resonance spectroscopy: in vivo magnesium
      measurements in the skeletal muscle of normal subjects.
AB  - 31P nuclear magnetic resonance spectroscopy was used to study the skeletal muscle
      of 33 normal males and 32 females. Free intracellular magnesium levels and the
      ratios of the phosphorus metabolites were determined. Males had significantly
      lower free magnesium levels (499.8 microM +/- 26.3 microM vs. 530.7 microM +/-
      36.0 microM, P = 0.001, d.f. = 63, analysis of variance). The free magnesium
      level (rs = -0.5431, P = 0.001) and the phosphocreatin/Inorganic phosphate ratio
      in males (rs = -0.4102, P = 0.018), and the phosphocreatine/Inorganic phosphate
      ratio in females (rn = -0.4759, P = 0.009) fell with the increasing Minnesota
      Heart Health Program Questionnaire score.

PMID- 8875422
TI  - Power efficient on-resonance saturation pulses for magnetization transfer in
      magnetic resonance imaging.
AB  - A family of new on-resonance saturation pulses for magnetization transfer in MRI
      is proposed. These pulses can be represented as a product of a shaped function
      and a cosine function. The shaped function can have many different forms, one of
      which is a Gaussian function. The experimental results on a 1.0 T whole body
      scanner show that the new on-resonance pulses are more efficient for
      magnetization transfer than either on-resonance binomial sequence pulses or off
      resonance Gaussian pulses at the same power level.

PMID- 8875423
TI  - Practical implementation of single-voxel double-quantum editing on a whole-body
      NMR spectrometer: localized monitoring of lactate in the human leg during and
      after exercise.
AB  - The classical double-quantum editing sequence 90 degrees,x-tau-180 degrees y-tau
      90 degrees x-t1-90 degrees x-tau-180 degrees y-tau-AQ (tau = 1/4J) was rendered
      volume selective, by making slice selective the first 90 degrees pulse and the
      two 180 degrees pulses. Using simple rules to ensure optimum radio frequency
      phase coherence, this single-voxel editing sequence, reminiscent of a basic PRESS
      localization technique, was implemented on a whole-body 3 T spectrometer, and in
      vitro editing of lactate methyl protons was demonstrated without any significant
      loss in intrinsic sensitivity. The effectiveness of the proposed approach in vivo
      was also illustrated through the localized monitoring of lactate in the human leg
      during and after exercise.

PMID- 8875424
TI  - Tuned fiducial markers to identify body locations with minimal perturbation of
      tissue magnetization.
AB  - A fiducial marker is described in which a small cell containing a short T1
      solution is surrounded by single- or quadrature-tuned windings. It is shown how
      these can be used to enhance small externally applied RF pulses, which do not
      significantly perturb the magnetization of the tissue, to excite the fiducial
      sample, and get substantial signals from it. The fiducials can be used to mark
      locations on the body unambiguously for, for example, frameless stereotaxy, and
      to identify coils, catheters, or other inserted devices.

PMID- 8875425
TI  - Noise in MRI.
AB  - This study analyzes the signal-to-noise ratio (SNR) in magnetic resonance
      imaging. The factors that determine the SNR are derived starting from basic
      principles. The SNR, for a given object, is shown to be proportional to the voxel
      volume and the square root of the acquisition time. The noise generated by the
      body is derived using a cylindrical model and is shown to be proportional to the
      square of the radius and the square root of the length.

PMID- 8875426
TI  - 29Si NMR and blood silicon levels in silicone gel breast implant recipients.

PMID- 8875427
TI  - Are neurotrophins synaptotrophins?

PMID- 8875428
TI  - Dynamics of synaptic vesicles in cultured spinal cord neurons in relationship to
      synaptogenesis.
AB  - The dynamics of synaptic vesicles (SVs) during the development of presynaptic
      specializations in cultured Xenopus spinal cord neurons was studied with the
      fluorescent vesicular probe FM1-43. In naive neurons that have not contacted
      synaptic targets, packets of SVs are distributed along the entire neurite and are
      quite mobile. The interaction with the synaptic target, such as a muscle cell or
      a latex bead coated with basic fibroblast growth factor, results in the
      localization and immobilization of SV packets at the contact site. Depolarization
      resulted in exocytosis of SVs in both naive and target-contacted neurites.
      Okadaic acid, a phosphatase inhibitor, caused a dispersal of SV packets in both
      naive and target-contacted neurites. Thus, prior to target contact, SVs are
      already organized into packets capable of release and recycling by a
      phosphorylation-dependent mechanism. Target interaction then recruits and anchors
      these functional SV packets into forming the presynaptic nerve terminal. With
      fluorescent phalloidin as a probe, F-actin was found to colocalize with SV
      clusters at bead-neurite contacts. Although okadaic acid caused a dispersal of
      SVs at the beads, F-actin localization there was relatively resistant to this
      drug treatment. This suggests that SVs become localized at the target by
      interacting with an actin-based cytoskeletal specialization in a phosphorylation
      sensitive manner. The induction of this cytoskeletal specialization by the target
      may be an early event in presynaptic differentiation.

PMID- 8875429
TI  - Overexpression of 2',3'-cyclic nucleotide 3'-phosphodiesterase in transgenic mice
      alters oligodendrocyte development and produces aberrant myelination.
AB  - The function of the intracellular protein 2',3'-cyclic nucleotide 3'
      phosphodiesterase (CNP) of oligodendrocytes (ODC) is unknown. We have now
      generated several homozygous transgenic mouse lines in which the human CNP gene
      is overexpressed up to sixfold, revealing new insights into early stages of
      myelinogenesis. Although no behavioral phenotype is immediately apparent,
      abnormalities of ODC and their myelin sheaths are striking. These are manifested
      as redundant myelin membrane and intramyelinic vacuoles, as well as lack of
      myelin compaction concordant with failure of the cytoplasmic leaflets of compact
      myelin to fuse. Further, ODC that overexpress CNP appear to mature earlier in
      development, resulting in earlier maximum gene expression for myelin basic
      proteins and proteolipid protein. These results indicate that CNP is an early
      expressed regulator of cellular events that culminate in CNS myelination.

PMID- 8875430
TI  - Molecular cloning of a novel type I receptor serine/threonine kinase for the TGF
      beta superfamily from rat brain.
AB  - Growth factors belonging to the TGF beta superfamily bind to and signal through a
      receptor complex comprising two transmembrane serine/threonine kinases, called
      type I and type II. Each receptor is responsible for the signaling of the
      individual TGF beta superfamily members. So far, five type II and six type I
      receptors have been cloned from mammalian sources. We report here the molecular
      cloning of a novel type I receptor serine/threonine kinase, ALK7 (activin
      receptor-like kinase 7), from rat brain. ALK7 shows a significant sequence
      similarity with TGF beta RI and ActRIB in the intracellular kinase domain and is
      quite distinct from other type I receptors in the extracellular domain. ALK7 mRNA
      is expressed in embryonic and in adult rat brain, where it was localized in
      superficial layers of the forebrain, the CA3 pyramidal subfield of hippocampus,
      the basal ganglia, the thalamus, and the cerebellar cortex. The functionality of
      the receptor was demonstrated by the identification of a constitutively active
      point mutant of ALK7 that activates the TGF beta/activin-responsive reporter
      without any ligand stimulation. Although the endogenous ligand for ALK7 has yet
      to be identified, its extensive anatomic distribution in brain, gut, spleen, and
      lung suggests important roles for this orphan receptor.

PMID- 8875431
TI  - TNF alpha inhibits Schwann cell proliferation, connexin46 expression, and gap
      junctional communication.
AB  - Schwann cell responses to nerve injury are stimulated, in part, by inflammatory
      cytokines. This study compares changes in the phenotype of cultured Schwann cells
      after exposure to the cytokine tumor necrosis factor (TNF)-alpha or the mitogen
      neu differentiation factor (NDF)-beta. TNF alpha inhibited proliferation in a
      dose-dependent manner without altering Schwann cell survival. TNF alpha also
      reduced both gap junctional conductance and Lucifer yellow dye coupling between
      Schwann cells. Moreover, both Po and glial fibrillary acidic protein (GFAP)
      immunoreactivity were reduced. By contrast, NDF beta initially had little effect
      on cell division although it reduced junctional coupling within 8 h. However, by
      48 h, NDF beta stimulated proliferation with a concomitant increase in coupling.
      Dividing Schwann cells (BrdU+) were preferentially dye coupled compared to
      nondividing cells, indicating an association between proliferation and coupling.
      Moreover, cultured Schwann cells expressed connexin46 mRNA and protein, and
      changes in the levels of the protein correlated with the degree of proliferation
      and coupling. The data thus provide evidence for cytokine-induced modulation of
      Schwann cell antigenic phenotype, proliferation, and gap junction properties.
      These observations suggest that enhanced gap junctional communication among
      Schwann cells after nerve injury could help to coordinate cellular responses to
      the injury, and that TNF alpha may be a signal which terminates proliferation as
      well as junctional communication.

PMID- 8875432
TI  - Altered connexin expression after peripheral nerve injury.
AB  - The identification of connexin32 (Cx32) in myelinating Schwann cells and the
      association of Cx32 mutations with peripheral neuropathies suggest a functional
      role for gap junction proteins in the nerve. However, after nerve crush injury,
      Cx32 expression dramatically decreases in Schwann cells in the degenerating
      region, returning to control levels at newly formed nodes of Ranvier and Schmidt
      Lantermann incisures by 30 days. The present study examined increases in
      expression of other connexins that occur after peripheral nerve injury. A 56/58
      kDa connexin46 (Cx46) protein species was detected in adult rat sciatic nerve,
      along with very low levels of Cx46 mRNA. However, by 3 days after crush injury,
      coincident with changes in Schwann cell phenotype, Cx46 mRNA rapidly increased in
      the degenerating regions. Additionally, the 56/58-kDa Cx46 protein species
      present in adult nerve decreased and a 53-kDa Cx46 species, which was also
      present in cultured Schwann cells, became apparent. Connexin43 (Cx43) mRNA and
      protein, which was localized to perineurial cells in adult nerve, dramatically
      increased in endoneurial fibroblasts in the crush and distal regions by 3 days,
      coincident with macrophage infiltration. By 12 days after injury, Cx43 decreased
      and was comparable to normal nerve. These results suggest that enhanced
      expression of Cx46 and Cx43, by nonneuronal cells, may be important for the
      injury and regenerative responses of peripheral nerves.

PMID- 8875433
TI  - "Expression patterns of two murine homologs of Drosophila single-minded suggest
      possible roles in embryonic patterning and in the pathogenesis of Down
      syndrome.".

PMID- 8875434
TI  - Chronic administration of a new potent agonist of growth hormone- releasing
      hormone induces compensatory linear growth in growth hormone-deficient rats:
      mechanism of action.
AB  - To assess the efficacy of a potent agonist analog of GH-releasing hormone (GH
      RH), [Dat1,Gln8,Orn12,21,Abu15,Nle27,Asp28,A gm29]hGH-RH(1-29) (JI-38), we
      investigated the effects of its chronic administration on growth responses in
      monosodium glutamate (MSG)-lesioned and normal young rats. Body weight (BW), body
      length (BL), tibia length (TIL), and tail length (TAL) were monitored. Basal
      serum GH concentrations, GH responses to bolus injections of GH-RH, pituitary GH
      and serum IGF-I concentrations were measured by RIA. Pituitary GH-RH receptor
      concentration and binding affinity was also evaluated after the treatment.
      Neonatal treatment with MSG resulted, as expected, in blunted growth and a
      decrease in serum and pituitary GH concentration and serum IGF-I levels. A
      reduction in GH-RH receptor concentration, associated with increased binding
      affinity of the GH-RH receptor was also found. Chronic administration of GH-RH
      agonist JI-38 in doses of 2 micrograms at 12-hour intervals for 2 weeks markedly
      increased the GH responsiveness to GH-RH and stimulated growth, with MSG-treated
      animals achieving the growth rate of normal controls. Acceleration of growth was
      associated with stimulated GH synthesis and IGF-I secretion, although basal serum
      GH levels did not change. Pituitary GH-RH receptor concentration and binding
      affinity were not significantly modified by the treatment. Treatment of normal
      young growing rats with agonist JI-38 did not further increase the normal growth
      acceleration in these rats, but stimulated the GH synthesis and augmented the GH
      secretory responsiveness. The treatment of MSG-lesioned rats with GH-RH agonist
      was generally more effective in female than in male animals, and in some cases
      masked the sex differences in growth rate. Our findings provide the first
      evidence that the blunted growth rate of the MSG-lesioned rats is associated with
      a decreased pituitary GH-RH receptor concentration. Our work demonstrates that
      administration of GH-RH agonist JI-38 is able to restore the normal growth rate
      of the GH-deficient rats by stimulating GH synthesis and IGF-I secretion.

PMID- 8875435
TI  - Pituitary growth hormone-releasing factor receptor expression in normal and dwarf
      rats.
AB  - Growth hormone-releasing factor (GRF) regulates GH release and somatotrope
      proliferation via a specific G-protein-coupled receptor. Little is known about
      the endocrine factors that regulate the expression of the GRF receptor (GRF-R) in
      the pituitary gland. We have developed a sensitive solution hybridization/RNAse
      protection assay for GRF-R mRNA in rat pituitary extracts. GRF-R transcripts were
      readily detectable in similar amounts in normal male and female rats, but were
      markedly reduced in extracts from age-matched growth hormone (GH)-deficient dwarf
      (dw) rats of either sex. The reduced GRF-R expression would appear to reflect
      somatotrope hypoplasia rather than GH deficiency per se since a similar reduction
      in GRF-R expression was seen in a transgenic model of dominant dwarfism, whereas
      GRF-R expression was significantly elevated in rats with GH deficiency induced by
      hypothyroidism. We were unable to demonstrate significant effects on GRF-R
      expression with infusions of human GH (hGH) or insulin-like growth factor 1,
      which stimulate growth in dw rats, but dexamethasone treatment induced a
      significant, time-related increase in GRF-R mRNA levels. We conclude that this
      assay can usefully quantify pituitary GRF-R expression in normal rats, and its
      reduction in two different strains of mutant dwarf rats with somatotrope
      hypoplasia.

PMID- 8875436
TI  - Sex-related alterations in hypothalamic growth hormone-releasing hormone mRNA-but
      not somatostatin mRNA-expressing cells in genetically obese Zucker rats.
AB  - The possibility that the growth hormone (GH) suppression associated with obesity
      is due to alterations in hypothalamic GH-releasing hormone (GHRH) and/or
      somatostatin (SRIH) has been considered, but the data are not consistent. In the
      present study, we sought to clarify the roles of GHRH and SRIH in obesity by
      using in situ hybridization to localize and quantify the level of expression of
      GHRH mRNA- and SRIH mRNA-containing neurons in the hypothalamus of male and
      female lean and obese Zucker rats (12 weeks of age; n = 6 per group). In lean
      animals, the number of GHRH mRNA-expressing cells in the arcuate nucleus and SRIH
      mRNA-containing neurons in the periventricular nucleus was 2- to 3-fold higher in
      males compared to females. The obese phenotype in the male was associated with a
      striking reduction in arcuate GHRH mRNA expression, both in terms of number of
      cells (-71%; p < 0.01) and grains/cell (-44%; p < 0.05). In contrast, in obese
      females, there was a marked augmentation (+ 175%; p < 0.05) in the number of GHRH
      mRNA-containing cells in the arcuate nucleus compared to their lean littermates.
      The small population of GHRH mRNA-containing neurons of the ventromedial nucleus
      was not modified in male obese rats, while it was considerably increased (p <
      0.05) in obese females. Neither the number of labeling density of SRIH mRNA
      containing neurons in the periventricular and arcuate nuclei of obese rats of
      either sex was changed when compared to their sex-matched lean counterparts.
      These results demonstrate that: (1) the obese male Zucker rat exhibits a marked
      diminution in hypothalamic GHRH mRNA expression, while a reverse pattern is
      evident in the obese female; (2) hypothalamic SRIH mRNA-containing neurons are
      not significantly altered in obese rats of both sexes. Our findings suggest that
      the impaired GH secretion of the obese Zucker rat is due, at least in part, to
      alterations in hypothalamic GHRH gene expression and that SRIH does not play a
      major role.

PMID- 8875437
TI  - Increased galanin and neuropeptide-Y immunoreactivity within the hypothalamus of
      ovariectomised ewes following a prolonged period of reduced body weight is
      associated with changes in plasma growth hormone but not gonadotropin levels.
AB  - Manipulation of diet is known to affect the secretion of the gonadotropins and
      growth hormone (GH). The former are under the direct regulation of hypothalamic
      gonadotropin-releasing hormone (GnRH) and the latter is under the dual control of
      GH-releasing hormone (GHRH) and somatostatin (SRIH). At the level of the
      hypothalamus, both galanin (GAL) and neuropeptide Y (NPY) are thought to regulate
      the secretion of the above releasing and inhibiting factors. Both peptides are
      also potent orexigenic agents. We have studied ovariectomised ewes that were
      either well-fed (HIGHs) or underfed (LOWs) and used immunocytochemistry and image
      analysis to measure the levels of GAL and NPY in hypothalamic nuclei in which
      GnRH, GHRH and SRIH are found and which are also involved in the regulation of
      appetite and feeding. The sheep were given a normal diet or a restricted diet for
      15 months. Four pairs of ewes were then blood-sampled to measure GH, luteinising
      hormone (LH), and follicle-stimulating hormone (FSH) and then killed for recovery
      of the brains. After perfusion, cryostat sections were cut through the entire
      hypothalamus, mounted, and stained fro NPY or GAL. All treatments and analyses
      were performed in pairs. The number of immunoreactive cells, density of terminals
      and total immunoreactivity (IR) were quantified by image analysis by sampling 6
      16 subareas (depending on region) on sections through the pre-optic area (POA),
      paraventricular nucleus (PVN), arcuate nucleus (ARC) and median eminence (ME).
      Mean (+/- SEM) live weight of the LOWs was significantly (p < 0.0001) lower than
      that of the HIGHs (37.6 +/- 0.6 kg vs. 60.6 +/- 0.5 kg). There was no difference
      in the plasma levels of LH and FSH but the area under the GH curve (ng/ml/h) was
      significantly (p < 0.0001) greater in the LOWs (320 +/- 40.9 vs. 67.3 +/- 16.1).
      There was an increased number of cells staining for NPY but not GAL in the ARC/ME
      of the LOWs. Nevertheless, the oveall level of immunostaining for both peptides
      was increased in the LOWs. GAL IR was restricted to the mediobasal hypothalamus.
      In the LOWs, the density of NPY terminal fields in each area of the ARC was
      significantly (p < 0.05) increased. Food restriction also increased the density
      of NPY terminals in the POA and PVN (p < 0.025) but not in the ME. These data
      indicate that a dietary manipulation which affects GH secretion but not the
      gonadotropins may be mediated by NPY and GAL neuronal systems in specific brain
      regions within the hypothalamus.

PMID- 8875438
TI  - Stimulatory effects of vasoactive intestinal peptide and pituitary adenylate
      cyclase-activating peptide on tuberoinfundibular dopaminergic neuron activity in
      estrogen-treated ovariectomized rats and their correlation with prolactin
      secretion.
AB  - The effects of central administration of vasoactive intestinal peptide (VIP) and
      pituitary adenylate cyclase-activating peptide (PACAP) on hypothalamic
      tuberoinfundibular dopaminergic neuron activity and serum prolactin (PRL) levels
      were reported. Adult female Sprague-Dawley rats overiectomized for 2 weeks,
      implanted with subcutaneous estrogen-containing capsules and
      intracerebroventricular (i.c.v.) cannulae for 6 days were used for experiments.
      I.c.v. injections of VIP or PACAP were performed in conscious rats in the
      morning, and the injected rats were decapitated at various times afterwards.
      Serum sample and the median eminence tissue were collected from each rat. The
      levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4
      dihydroxyphenylalanine (DOPA) in the median eminence were determined by high
      performance liquid chromatography with electrochemical detection. Serum PRL
      levels were determined by radioimmunoassay. I.c.v. administration of VIP (1
      microgram/3 microliter) significantly increased median eminence DOPAC/DA ratio at
      30 min, and serum PRL level at 15 min. The same dose of VIP (1 microgram), but
      not higher (10 micrograms) or lower (0.1 microgram), was also effective in
      stimulating the median eminence DOPA accumulation 35 min after the injection. The
      effect of VIP (1 microgram) on median eminence DOPA could be blocked by
      coadministration of a VIP antagonist, VIP6-28 in 10- and 30-, but not in 1- or
      0.1-microgram doses. On the other hand, i.c.v. administration of PACAP (10
      micrograms) stimulated median eminence DOPAC and lowered serum PRL levels at 30
      min. All doses of PACAP used (0.1, 1 and 10 micrograms/ rat, i.c.v.)
      significantly increased median eminence DOPA concentrations at 60 min. The
      stimulatory effect of PACAP (0.1 microgram) on median eminence DOPA could also be
      blocked by coadministration of a PACAP antagonist, PACAP6-38 (in 10 to 100 x
      higher doses). In summary, central administration of either VIP or PACAP
      exhibited a stimulating effect on TIDA neuron activity through specific
      receptors. Serum PRL levels, however, were stimulated and inhibited by VIP and
      PACAP, respectively.

PMID- 8875439
TI  - Colocalization of progesterone receptor and somatostatin immunoreactivities in
      the hypothalamus of the male and female guinea pig.
AB  - A double-label immunofluorescence technique was used to determine whether
      progesterone receptor (PR)-containing neurons in the preoptic area and
      hypothalamus also contain somatostatin (SOM) in both the male and female guinea
      pig. Animals were gonadectomized, primed by estradiol to induce PR and injected
      intracerebroventricularly with colchicine to visualize SOM-immunoreactive (SOM
      IR) neurons. The only sites of significant overlap between the two
      immunoreactivities were the medial preoptic nucleus, the periventricular preoptic
      and hypothalamic regions, the arcuate nucleus (Ar) and the ventrolateral nucleus
      (VL). No sex differences were detected at this level. In the preoptic area and
      the periventricular regions, no SOM-IR neurons were shown to have PR. In the Ar,
      only very few SOM-IR perikarya were found to be also PR-IR. SOM varicosities
      appeared in close proximity to neurons with PR-containing nuclei. Within the VL,
      in the female as well as in the male, many SOM-IR cells were also IR for PR. This
      colocalization persisted throughout the rostrocaudal extent of the nucleus but
      our quantification revealed a significant sex difference in the percentage of PR
      IR neurons with SOM in the caudal VL. These results provide neuroanatomical
      evidence that progesterone may exert its effect directly upon more than one third
      of SOM-synthesizing cells in the medial and caudal regions of VL, a site which
      plays a key role in the control of sexual behavior.

PMID- 8875440
TI  - The luteinizing hormone but not the cortisol response to arginine vasopressin is
      prevented by naloxone and a corticotropin-releasing hormone antagonist in the
      ovariectomized rhesus monkey.
AB  - In the primate, arginine vasopressin (AVP) is known to activate the hypothalamo
      pituitary-adrenal axis and to inhibit LH secretion. In the present study, we
      investigate the role of the endogenous opioid peptides and corticotropin
      releasing hormone (CRH) in these processes. Adult ovariectomized rhesus monkeys
      bearing a chronic cannula in the lateral ventricle for intraventricular (i.c.v.)
      infusion were used. In experiment 1, the effects of 5-hour i.c.v. infusions of
      saline (n = 7), AVP (50 micrograms/h, n = 7), naloxone (2 mg bolus + 2 mg/h i.v.,
      n = 4) and AVP plus naloxone (n = 4) on LH and cortisol secretion were
      investigated. As compared to saline and naloxone alone, LH pulse frequency was
      significantly decreased by AVP (p < 0.05) and by 5 h, the mean LH expressed as a
      percentage from the 3-hour baseline was also significantly reduced (saline 100.9
      +/- 5.1%; naloxone 112.3 +/- 2.9%; AVP 63.3 +/- 8.2%). Coadministration of
      naloxone abolished the effects of AVP on LH (107.3 +/- 12.1% of baseline). AVP
      increased cortisol secretion (p < 0.05 vs. baseline), but naloxone did not
      prevent the increase. In experiment 2, the LH and cortisol responses to AVP were
      compared in the absence and presence of a CRH antagonist. The antagonist was
      infused intraventricularly at two doses: 60 and 180 micrograms/h. At both doses,
      the inhibitory effect of AVP on LH was significantly attenuated (at 4 h, 86.9 +/-
      3.2% of baseline; NS vs. saline). However, the CRH antagonist did not block the
      AVP-induced increase in cortisol. The results confirm previous evidence in the
      primate of a role of vasopressin in inhibiting the hypothalamo-pituitary-gonadal
      axis and demonstrate a role of hypothalamic opioid peptides in this process. They
      also demonstrate that, although CRH is a prerequisite for AVP's action on the
      hypothalamo-pituitary-gonadal axis, AVP can stimulate the adrenal axis in the
      primate in the presence of decreased CRH activity.

PMID- 8875441
TI  - Age-dependent suppression of nocturnal growth hormone levels during sleep
      deprivation.
AB  - Although the major daily peak in plasma growth hormone (GH) level normally occurs
      during the early part of nocturnal sleep, it is known that in about one quarter
      of young healthy men, peaks in circulating human GH occur before sleep onset.
      Possible factors associated with these nocturnal peaks were investigated in the
      absence of sleep, including subjectively defined sleepiness,
      electroencephalographically defined drowsiness and short lapses into sleep,
      measures of cortisol and temperature. Healthy men between the ages of 20 and 34
      years were studied in a between-subjects design, 16 assigned to a sleep
      deprivation group, and 16 age matched and assigned to a group permitted to sleep.
      The average GH peak level in the sleeping subjects was 19.9 micrograms/l (+/- 8.4
      SD). In the sleep-deprivation group there was a wide range of nocturnal GH
      patterns, from no detectable rise to normal nocturnal levels (average peak of
      10.5 +/- 10.0 micrograms/l). Within the narrow age range sampled, age, body mass
      index, temperature and cortisol failed to predict nocturnal GH peak in the
      sleeping group, but regression analysis found age to be a significant negative
      predictor of nocturnal GH peak level in sleep-deprived subjects. All sleep
      deprived subjects who had peak GH levels over 7 micrograms/l were 24 years of age
      or less. Subjective sleepiness and electroencephalographically defined drowsiness
      failed to predict either the peak level of GH during sleep deprivation or the
      cumulative amount measured across the night. These results suggest that the well
      known suppressive effect of sleep deprivation on GH secretion is an age-dependent
      phenomenon which evolves during early adulthood.

PMID- 8875442
TI  - Effects of intravenously infused pituitary adenylate cyclase-activating
      polypeptide on adenohypophyseal Hormone secretion in normal men.
AB  - The possible stimulatory effects of an intravenous infusion of increasing amounts
      of pituitary adenylate cyclase-activating polypeptide (PACAP) on anterior
      pituitary hormone secretions were evaluated in humans. Successively increasing
      doses of PACAP-38 (2, 4 and 8 pmol.kg-1.min-1; each dose for 20 min) were infused
      i.v. in 7 normal male subjects. On a different occasion, the same subjects were
      tested with vasoactive intestinal peptide (VIP; 4 pmol.kg-1.min-1 for 60 min).
      Circulating GH, ACTH, PRL, TSH and gonadotropin concentrations were measured
      before PACAP infusion and every 20 min, just before increasing the infusion dose
      of PACAP. Blood samples were taken before and every 15 min after the beginning of
      VIP administration. Serum levels of GH, TSH and gonadotropins did not change
      during PACAP or VIP infusion. Circulating ACTH and PRL concentrations were not
      modified by the infusion of the lowest dose of PACAP, whereas they were
      significantly increased in a dose-response fashion when higher amounts of PACAP
      were given. PRL, but not ACTH levels were significantly increased by VIP
      infusion. These data show for the first time in humans that ACTH and PRL
      secretions from the anterior pituitary gland are stimulated by the systemic
      administration of PACAP. In addition, since VIP stimulated only PRL secretion,
      PACAP-induced ACTH release appears to be mediated by specific receptors.

PMID- 8875443
TI  - Contour of the GnRH pulse independently modulates gonadotropin secretion in the
      human male.
AB  - GnRH pulse frequency, amplitude, and interpulse interval have all been
      demonstrated to regulate gonadotropin secretion individually. We tested the
      hypothesis that the contour of the GnRH pulse also modulates gonadotropin output
      in 10 men with isolated GnRH deficiency in whom a fixed GnRH dose was
      administered at a constant physiologic frequency by either instantaneous bolus or
      by 1-, 5-, or 30-min infusions. LH, FSH and free alpha subunit (FAS) responses
      were also compared to spontaneous gonadotropin secretion in normal adult men.
      While the LH and FAS pulses following the instantaneous bolus and 1-min infusion
      of GnRH were indistinguishable, further increases in the duration of gonadotrope
      stimulation by GnRH were associated with progressive decreases in all parameters
      of gonadotropin secretion (mean levels, amplitude, peak levels, AUC). FSH
      secretion was also decreased following variations in the contour of the GnRH
      pulse, although overall changes were less dramatic than for LH and FAS. The LH
      pulses following the bolus GnRH stimulation were indistinguishable from
      spontaneous LH pulses occurring in normal men whereas those stimulated by the 1-,
      5-, and 30-min infusions of GnRH became progressively blunted with the lowest
      levels of secretion occurring after the longest infusion. In sharp contrast, FAS
      pulse parameters in the GnRH-deficient subjects greatly exceeded those of normal
      men regardless of the contour of the GnRH stimulus, whereas mean FSH levels were
      all modestly (although significantly) higher than those of normal adult men.
      These results demonstrate that the pituitary is sensitive to subtle changes in
      the contour of the GnRH stimulus, with a more prolonged duration of GnRH
      stimulation resulting in a diminished pituitary response. Alterations of the
      contour of endogenous GnRH secretion may represent an additional mechanism for
      altering gonadotrope function and provide additional evidence for the
      differential regulation of LH, FAS, and FSH by GnRH. However, the previously
      reported elevated levels of FAS secretion in GnRH-deficient men undergoing long
      term GnRH replacement are not explained by abnormalities of GnRH contour.

PMID- 8875444
TI  - Decreased senile plaque density in Alzheimer neocortex adjacent to an omental
      transposition.
AB  - Post-mortem studies of the brain of an Alzheimer patient indicate fewer senile
      plaques in the crests of cortical gyri underneath an omental transposition than
      in neighboring cortical areas.

PMID- 8875445
TI  - CNS immunological modulation of neural graft rejection and survival.
AB  - Neural transplantation therapy as a possible alternative treatment for
      neurological movement disorders, such as in Parkinson's disease (PD), has
      accentuated research interest on the immune status of the central nervous system
      (CNS). Most animal studies concerned with neural transplantation for the
      treatment of PD have utilized dopamine (DA) neurons from tissues of the embryonic
      ventral mesencephalon. Rat embryonic DA neurons, grafted either as solid blocks
      or dissociated into a cell suspension and stereotaxically injected
      intraparenchymally into a rat lesion model of PD, have been shown to survive and
      form connections with the host brain, and ameliorate the behavioral deficits of
      PD. Similarly, studies on nonhuman primate models of PD provide considerable
      support for neural transplantation of DA neurons as an experimental clinical
      procedure for the treatment of PD. To this end, experimental clinical trials have
      been centered upon transplantation of the embryonic ventral mesencephalic cells
      for PD patients. Although not conclusive, the findings from clinical studies have
      provided some evidence that most patients with marked increases in fluorodopa
      uptake (indicating graft survival) have been immunosuppressed. Furthermore,
      immune reactions have been observed in rats xenografted with human embryonic
      tissue. Of note, embryonic ventral mesencephalic tissues compared to adult
      tissues produce better morphological and long-lasting behavioral amelioration of
      the neurobehavioral deficits of PD, thus advocating the use of grafts from young
      donors (embryo) to circumvent the CNS immune rejection. The possible graft
      rejection due to CNS immune reactions, coupled with the social and ethical
      problems surrounding the use of embryonic neural tissue, and the logistical
      problems concerning tissue availability have prompted the development of
      alternative sources of DA-secreting cells. To circumvent these obstacles, several
      methods have been suggested including the use of immunosuppressants such as
      Cyclosporine-A, transplantation of autografts, polymer-encapsulated DA-secreting
      cells, co-culturing and co-transplantation of DA-secreting cells with
      microcarrier beads, with Sertoli cells, or with fragments of a monoclonal
      antibody that can mask the MHC class I antigens, and genetically modifying cells
      that can withstand CNS immune reactions. Some of these techniques allow
      transplantation of allograft (same species transplantation), or even xenograft
      (cross species transplantation) without immunosuppression of the recipient. We
      discuss recent CNS immunosuppression techniques that pose some promise for
      enhanced survival of neural grafts. When possible, advantages and disadvantages
      of each method are presented. Hopefully, such critical analysis of different
      immunosuppression techniques will produce innovated ideas that will lead to a
      better understanding of CNS immune response and its modulatory function on graft
      rejection and survival.

PMID- 8875446
TI  - Microsurgical anatomy of the arachnoidal trabecular membranes and cisterns at the
      level of the tentorium.
AB  - A clear and thorough understanding of the neuroanatomical structures of the
      subarachnoid cisterns is important because they provide natural pathways to
      intracranial arteries, veins, and nerves during microvascular procedures without
      disturbing surrounding important brain structures. Using a surgical microscope,
      we examined the microsurgical anatomy of the trabecular membranes and
      subarachnoid cisterns in 20 adult cadaver brains. The brains were immersed in
      Ringer's solution and air was injected into the subarachnoid cisterns while the
      brains remained submerged in solution. We identified seven trabecular membranes
      that limit six cisterns. We specifically looked at the anatomical relationship
      between the trabecular membranes and cisterns and their corresponding vessels and
      cranial nerves. The cistern divisions and the dispositions of trabecular
      membranes were closely related to the vascular division patterns of the principal
      brain arteries.

PMID- 8875447
TI  - Transcranial Doppler and systemic hemodynamic studies in septic shock.
AB  - The present study outlines the relationship between cerebral and systemic
      hemodynamics in patients with septic shock. Sepsis is an immune mediated systemic
      disease in which the systemic vascular resistance (SVR) often decreases as a
      result of a Gram negative sepsis. The result is a hyperdynamic systemic
      circulation with redistribution phenomena in different organ systems. In order to
      study the effect of sepsis on cerebral vessels 20 patients with septic shock (12
      men, 8 women, mean age 57.9 years) were subjected to both pulmonary artery
      catheter and transcranial Doppler (TCD) monitoring. The data were correlated to
      the APACHE II score and outcome. The study showed that cerebral mean and end
      diastolic blood flow velocities (BFV) in the middle cerebral arteries
      significantly enhanced if the SVR-index decreases. In some patients a severely
      reduced SVRI (below 500 dynes.s/cm5.m2) was observed in combination with a
      downstroke latent steal phenomenon. TCD abnormalities were strongly related to
      disease severity and outcome. The increased BFV are explained by a mild vasospasm
      of the basal cerebral arteries. TCD appears to be a valuable tool to monitor the
      cerebral hemodynamics in these patients. They are particularly at risk for
      ischemic brain damage if they are subjected to therapeutic or spontaneous
      hyperventilation, which can potentially be detected by TCD.

PMID- 8875448
TI  - Neurosarcoidosis following augmentation mammoplasty with silicone.
AB  - We report a patient with neurosarcoidosis, which developed 22 years after
      augmentation mammoplasty by the injection of silicone gel. She presented with
      bilateral hilar lymphadenopathy, left-sided lower cranial nerve palsies (8th,
      9th, and 10th), and vestibular ataxia, which improved following the
      administration of prednisolone. Biopsy of the breast nodules showed granulomatous
      changes identical with those of sarcoidosis, while infrared spectrophotometry
      disclosed that the nodules contained polydimethylsiloxane, a major component of
      the silicone gel injection. This is the first report of neurosarcoidosis
      following silicone mammoplasty.

PMID- 8875449
TI  - Prognostic value of complete response after the initial treatment for malignant
      astrocytoma.
AB  - To evaluate prognostic value of complete disappearance of the tumor mass in
      contrast enhanced computerized tomography after initial treatment, 81 patients
      with supratentorial malignant astrocytomas (57 anaplastic astrocytomas and 24
      glioblastomas) were divided into two groups. All complete response CR patients
      received the gross total resection (more than 95% resection). Average age of this
      group was significantly younger than that of noncomplete response patients (38.4
      vs. 49.7 years old, p < 0.05; Student t-test). In the complete response group,
      median survival duration was 58 months, 2-year survival rate was 77%, and 5-year
      survival rate was 34% compared to 12 months, 29%, and 10%, respectively, in the
      noncomplete response group. The outcome of CR group was significantly better (p <
      0.001; Wilcoxon test). Therefore, complete response at completion of the initial
      treatment is an important predictor of longer survival. Gross total resection is
      essential to obtain complete response and thus plays a crucial role in the
      initial treatment of malignant astrocytomas.

PMID- 8875450
TI  - Effects of nilvadipine (a dihydropyridine-type calcium entry blocker) on cerebral
      blood flow in acute experimental brain ischemia in rats.
AB  - The purpose of the present study was to examine the effect of nilvadipine (a
      dihydropyridine-type calcium entry blocker) on the cerebral circulation,
      experimental models of cerebral ischemia were used to measure abrupt changes in
      the cortical cerebral blood flow (CBF) at the 'penumbra' (the boundary region
      between the anterior cerebral artery (ACA) and the middle cerebral artery (MCA)).
      Left middle cerebral artery occlusion (MCAO) was performed in Sprague--Dawley
      rats, and then 8 or 16 micrograms kg-1 of nilvadipine was administered to two
      groups of the rats. The former group was referred to as the 8-MCAO(+) group (n =
      8), and the latter group, the 16-MCAO(+) group (n = 8). To a control group (n =
      8), only the solvent of nilvadipine was administered. After the administration in
      each group, CBF and the mean arterial blood pressure (MAP) were continuously
      measured for 60 min. The MAP in both the 8-MCAO(+) and 16-MCAO(+) groups was
      significantly lower than in the control group for 25 min after nilvadipine
      administration (Wilcoxon 2 sample test, p < 0.05). Also, the CBF in the 16
      MCAO(+) group was significantly lower (about 20%) for 55 minutes than that in the
      control group. On the other hand, the CBF in the 8-MCAO(+) group three minutes
      after nilvadipine administration was not significantly lower than in the control
      group (Wilcoxon 2 sample test). Our findings confirmed that nilvadipine (8
      micrograms kg-1) maintained CBF while lowering the blood pressure in the
      experimental model of acute cerebral ischemia.

PMID- 8875451
TI  - Molecular cloning of the rat NADH:ubiquinone oxidoreductase subunit and its up
      regulation in the facial muscle after denervation: detected by means of
      differential display.
AB  - The differential display method was applied to identify gene expression which is
      especially up-regulated in the rat denervated skeletal muscle. Total RNA from
      normal and denervated facial muscles was isolated, amplified by PCR using certain
      primers, and separated by electrophoresis on polyacrylamide gel. PCR products
      which were apparently higher in the operated than in the control side were cut
      out from the gel and subsequently sequenced. One of the cDNA fragments obtained
      in the present study showed about 80% identity in nucleotide sequence and about
      84% identity in amino acid sequence to one of the NADH: ubiquinone oxidoreductase
      (complex I) subunits from the bovine heart mitochondria (813). Complex I, the
      first and largest enzyme of the mitochondrial respiratory chain, transfers
      electrons from NADH to ubiquinone-10 (UQ-10). B13 is a 13 kDa subunit; deficiency
      of which causes incomplete or incorrect assembly of a functional complex I,
      resulting in one of the types of human mitochondrial myopathy. Northern blot
      analysis and in situ hybridization histochemistry confirmed that rat B13 mRNA
      expression was up-regulated after denervation and was distributed throughout
      whole muscle cell body. These findings suggest that up-regulation of the rat B13
      mRNA expression after denervation plays an important role in the effective
      electron transfer from NADH to UQ-10 in skeletal muscle cells, resulting in
      restriction of lipid peroxidation and biological tissue damage.

PMID- 8875452
TI  - Sphingomyelin changes in rat cerebral cortex during focal ischemia.
AB  - To better define the sphingolipid metabolism during focal brain ischemia, levels
      of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat
      cerebral cortex during focal ischemia produced by occlusion of the middle
      cerebral artery. Sphingomyelin began to decrease at 2 hours of ischemia and
      continued to decrease for 96 hours. In contrast, ceramide increased at 6 hours
      and increased to 4.2-fold at 96 hours after ischemia, and the fatty acid
      composition of ceramide was solely nonhydroxylated fatty acid similar to
      sphingomyelin. Hydroxylated fatty acid-linked cerebroside decreased at 6 hours of
      ischemia, whereas any significant decrease of nonhydroxylated fatty acid-linked
      cerebroside didn't occur for 96 hours of ischemia. There were no measurable
      changes in the levels of gangliosides. These results suggested that ceramide was
      produced in the cerebral cortex by the breakdown of sphingomyelin during early
      ischemia.

PMID- 8875453
TI  - Thrombolytic therapy with tissue plasminogen activator for prevention of
      vasospasm in experimental subarachnoid hemorrhage: its efficacy and problems.
AB  - We investigated the efficacy of two different tissue plasminogen activators (t
      PA) for preventing vasospasm after experimental subarachnoid hemorrhage (SAH) in
      rabbits. Intrathecal injection of Silteplase and Alteplase showed significant
      preventive action against vasospasm following SAH and thrombolytic effect. The
      low dose groups with both t-PA showed more preventive action on day 1 than the
      high dose groups. The data suggest that the determination of optimum dose of t-PA
      is essential in clinical use of t-PA.

PMID- 8875454
TI  - The effects of 2-chloroadenosine and deoxycoformycin on the ATP level, Na-K
      ATPase activity in experimental brain ischemia of gerbil.
AB  - The effect of 2-chloroadenosine, stable adenosine analog, and deoxycoformycin,
      adenosine deaminase inhibitor on brain ATP level and Na-K ATPase activity in
      ischemia were studied. The brain ATP level was increased after we administered
      both 2-chloroadenosine and deoxycoformycin, but Na-K ATPase activity did not
      change after deoxycoformycin. The results suggest that 2-chloroadenosine
      treatment influenced both the ATP production and membrane permeability due to
      cerebral ischemia. Deoxycoformycin did not protect the membrane permeability,
      although it increased the ATP production.

PMID- 8875455
TI  - Tyrosine phosphorylation and [Ca2+]i elevation induced by hemolysate in bovine
      endothelial cells: implications for cerebral vasospasm.
AB  - Endothelial cells are affected in the cerebral vasospasm that occurs at the time
      of erthyrocyte lysis in a subarachnoid clot. A red blood cell lysate was added to
      bovine pulmonary artery endothelial cells in vitro to determine whether
      hemolysate can trigger tyrosine kinase mediated cell signalling and if so,
      whether this signal is independent of the elevation of intracellular free calcium
      levels, [Ca2+]i induced by hemolysate. Hemolysate was found by Western blotting
      to induce a dose dependent increase in the level of tyrosine phosphorylation of
      two proteins, approximately 60 and 110 kD, that was maximal between 1 and 2 min.
      The biphasic increase in [Ca2+]i induced by hemolysate consists of a peak
      complete within 1 min which is the result of release of intracellular calcium
      stores and a plateau phase due to an influx of extracellular Ca2+. Addition of
      hemolysate to cells in the presence of EGTA indicated that an extracellular Ca2+
      influx is not required for the increases in tyrosine phosphorylation. Release of
      intracellular Ca2+ stores by thapsigargin, a Ca(2+)-ATPase inhibitor, was,
      however, found to increase the phosphotyrosine content of the same 60 and 110 kD
      proteins. Endothelial cells pretreated with tyrosine kinase inhibitors,
      tyrphostin 25 or genistein, before exposure to hemolysate blocked the plateau
      phase of the [Ca2+]i response indicating that tyrosine kinase activity is
      required for the influx. Ca2+ and phosphotyrosine mediated cell signalling
      induced by hemolysate in endothelial cells may be activated by a single component
      but represent distinct targets for possible control of the cerebral vasospasm
      response.

PMID- 8875456
TI  - Construction of 3-D arterial volume meshes from magnetic resonance angiography.
AB  - Finite element methods are well-suited for solving problems in arterial fluid
      dynamics, primarily due to their ability to handle flows in complex geometries.
      However, in order to use these computational methods to develop realistic models
      of pulsatile flow in intracranial arteries and associated aneurysms, it is
      necessary to construct a 3-D mesh, or grid, that accurately duplicates the
      arterial geometry of interest. In this paper, we present an efficient method to
      accurately develop realistic 3-D computational meshes of human intracranial
      arteries and aneurysms from serial magnetic resonance angiography images.
      However, these techniques may be applied to any other form of imaging data
      including computed tomographic angiography. First, raw grayscale images are
      segmented, converted to their binary form and arterial contours are extracted at
      each image slice. Next, the arterial contours are stacked and cubic splines are
      computed along the axial direction. This creates an affect similar to smooth
      integration in the axial direction and provides a set of points that define the 3
      D arterial surface geometry. Then, surface patches are constructed and merged. A
      surface mesh is then computed with the ability to locally vary the mesh density
      as desired. Finally, nodal points on the surface mesh are used to compute the
      finite element volume mesh. The 3-D volume mesh accurately describes the arterial
      geometry and is used to develop patient-specific computational fluid dynamic
      models of flow phenomena in intracranial arteries and aneurysms. These flow
      models are then suitable for investigating the hemodynamics of intracranial
      aneurysm formation and test the end-effects of various medical and surgical
      treatments.

PMID- 8875457
TI  - Mathematical modeling of AVM physiology using compartmental network analysis:
      theoretical considerations and preliminary in vivo validation using a previously
      developed animal model.
AB  - The development of computer modeling technique of cerebral arteriovenous
      malformations using circuit network analysis, validated with a previously
      developed animal model is presented. Such a malformation and its vascular
      connections are rendered into a complex system of interconnecting tubes, which is
      then simulated by an analogous electrical circuit using commercially available
      computer software. This methodology was tested using a swine model, of which a
      detailed computer model was constructed from anatomic and angiographic
      measurements of the cranial vessels. Flow conditions, before and after creation
      of the in vivo model, were predicted from the computer model and compared with
      previously reported in vivo measurements. Detailed analysis of flow within the
      CAVM nidus was also performed. There was a good correlation between the computer
      and in vivo models regarding changes in flow and pressure drop across the rete.
      Flow mapping within the nidus showed localized directional flow that was
      determined by global inputs, consistent with functional compartmentalization.
      This method of computer modeling appears promising for studying clinically
      relevant aspects of cerebral arteriovenous malformation pathophysiology. To our
      knowledge it is the first computer model to demonstrate functional
      compartmentalization.

PMID- 8875458
TI  - Repetitive hypoxic exposure of brain slices and electrophysiological responses as
      an experimental model for investigation of cerebroprotective measurements.
AB  - An in vitro hippocampal (CA 1 region, guinea pig) slice technique using repeated
      hypoxia was employed to model electrophysiological changes (DC-potentials and
      evoked potentials (EP) by stimulation of Schaffer-collaterals) occurring in the
      hypoxic CA1 pyramidal layer. A standardized neuronal response under repeated
      hypoxic conditions was observed in this model, consisting of disappearance of EP
      and a trend towards partially reversible, but progressive synaptic failure
      subsequent anoxic depolarisation (AD). Slices treated with the calcium antagonist
      nimodipine showed a prolongation of AD latency between the first and following
      hypoxias. So it seems possible to simulate hypoxic lesions of the brain tissue by
      using this in vitro slice model.

PMID- 8875459
TI  - Microdialytic monitoring during cerebrovascular surgery.
AB  - Using microdialysis, levels of metabolites in the extracellular fluid of the
      cerebral cortex were monitored during neurovascular surgery (9 aneurysm and 5
      extra-intracranial bypass operations). Our aim was to use microdialysis to detect
      any local ischemia which might be caused by brain retraction or temporary
      clipping. Parameters were therefore quantified whose levels in the dialysate are
      known to be influenced by ischemia (on-line pH, ascorbic acid, uric acid,
      glutathione, cysteine, glucose, lactate, glucose:lactate ratio). In the aneurysm
      series, on-line pH fell after introduction of the retractor, and in the majority
      of cases the other parameters also showed changes in accordance with ischemic
      conditions in the region of the probe. These changes disappeared at the end of
      retraction, or sometimes even before. During the bypass operations, there were no
      marked changes in on-line pH or in any of the measured parameters. However, in
      some of these patients values for the glucose:lactate ratio, ascorbic acid and
      uric acid lay outside the suggested basal levels for minimally disturbed cortex,
      indicating possible changes in metabolism caused by inadequate perfusion (carotid
      artery occlusion). We conclude that microdialysis is a sensitive method of
      detecting intraoperative changes in cerebral metabolism.

PMID- 8875460
TI  - Pulsation-pressure relationship in experimental aneurysms: observation of
      aneurysmal hysteresis.
AB  - In this study the pulsation-pressure relationship in an experimental model of
      aneurysms was analyzed. In addition, we have examined pulsatility of the
      aneurysmal wall reinforced by Guglielmi Detachable Coils (GDC). Bifurcation
      (BAn), aneurysms (LAn) and bilobar (BiA) aneurysms were produced in 15 mongrel
      dogs. The aneurysmal dome was constructed from a segment of the external jugular
      vein which was sutured to the window performed on the apex of bifurcation of the
      ECA and lingual artery (BAn) or on the ECA (LAn). One set of the GDC (diameter 5
      mm, length 20 cm) were inserted into the aneurysm. Intra-aneurysmal pressure,
      aneurysmal pulsation, ECG and femoral artery pressure were recorded. Results
      showed that an experimental aneurysm pulsates in synchrony with the intra
      aneurysmal pressure and aneurysmal pulsation is proportional to the aneurysmal
      size. Pulsation profile also depends on the aneurysmal type (BAn, LAn, BiA). The
      looped pressure-pulsation curve indicates that aneurysms exhibit property of
      hysteresis. For the same pressure the aneurysm is smaller during the ascending
      (systolic) portion of the blood pressure wave. Insertion of catheter into the
      aneurysm and subsequent release of the GDC did not elicit any measurable changes
      of the intra-aneurysmal pressure. Aneurysm reinforced by GDC showed smaller
      pulsation and the hysteresis was reduced as well. It was concluded that
      aneurysmal hysteresis could be an important factor resulting in degeneration of
      aneurysmal wall since it is known that hysteresis accelerates degeneration of all
      fibrous elements, predominantly of elastic fibers. GDC seems to buffer the intra
      aneurysmal hemodynamic forces and hence they might have a stabilizing effect on
      the aneurysmal wall.

PMID- 8875461
TI  - The pathology of charcot-marie-tooth disease and related disorders.
AB  - Approximately a quarter of a century ago, the disorders originally designated as
      Charcot-Marie-Tooth disease and Dejerine-Sottas disease were shown by combined
      clinical, electrophysiological and nerve biopsy studies to be genetically
      complex. In pathological terms they could be broadly classified into
      demyelinating neuropathies and axonopathies. Advances in the molecular genetics
      of these disorders, particularly for those with a demyelinating basis, have
      recently produced substantial new insights. The identification of mutations in
      genes for myelin proteins has provided the opportunity for investigating the
      precise mechanisms of these neuropathies, including the use of spontaneous and
      genetically engineered animal models.

PMID- 8875462
TI  - Prion protein genotype and pathological phenotype studies in sporadic Creutzfeldt
      Jakob disease.
AB  - A comparative semi-automated morphometric study was performed on the distribution
      of prion protein, spongiform change and astrocytosis in the brains of nine cases
      of sporadic Creutzfeldt-Jakob disease of differing genotype at the methionine
      valine polymorphism at codon 129 of the prion protein gene. Custom-designed image
      analysis software was used to produce objective figures for each of the different
      pathological features throughout 13 different areas of the brain used for
      analysis. A significant positive correlation was observed between prion protein
      deposition and astrocytosis in all cases and no significant correlation was
      observed between spongiform change and prion protein deposition. Different
      patterns of pathology were found to relate to codon 129 genotype; valine
      homozygosity favoured the targeting of pathology to deep grey matter structures,
      while methionine homozygosity favoured cortical targeting of pathology. These
      results provide evidence that prion protein deposition is closely associated with
      an astrocytic reaction and suggest that codon 129 genotype may influence the
      pathological phenotype.

PMID- 8875463
TI  - Parvalbumin and calbindin D-28 k immunoreactivity in dorsal root ganglia in
      acquired immunodeficiency syndrome.
AB  - Various degrees of neuronal degeneration have been found in lumbosacral dorsal
      root ganglia of patients with acquired immunodeficiency syndrome (AIDS). To
      characterize the subpopulations of primary sensory neurons affected in AIDS, we
      immunostained dorsal root ganglion tissues from 11 AIDS patients and six controls
      using antibodies to the calcium binding proteins, parvalbumin and calbindin D-28
      k. In controls, the proportion of neurons containing parvalbumin and calbindin
      was 18.0% and 22.4%, respectively. The majority of parvalbumin-positive neurons,
      which are thought to be proprioceptive neurons, were of medium to large size,
      while calbindin was found in both large- and small-sized neurons. The density of
      parvalbumin-immunoreactive neurons was reduced by 7.3% in AIDS patients, but the
      density of calbindin-immunoreactive neurons was preserved. Furthermore, in AIDS
      cases, the number of parvalbumin-positive neurons was reduced more in dorsal root
      ganglia in which human immunodeficiency virus (HIV) antigen was detected than in
      HIV-negative ganglia. These results suggest that specific subpopulations of
      sensory neurons positive for parvalbumin may be differentially affected over the
      course of AIDS, and that this could be related to peripheral neuropathy which
      frequently occurs in the late stages of AIDS.

PMID- 8875464
TI  - Plastic phenotype of human oligodendroglial tumour cells in vitro.
AB  - Human oligodendroglioma cells cultured in serum-supplemented media lose their
      oligodendrocytic antigenic markers and acquire astrocytic markers. However, after
      reimplantation in rodent brain, these cells re-express oligodendrocytic markers.
      This switch in human oligodendroglioma cell phenotype could result from the
      interplay of different stimuli in vitro vs in vivo The in vitro differentiation
      into astrocytes might result from non-physiological culture conditions. It is
      shown that human oligodendroglioma cells behave in a way similar to that of
      rodent bipotential 0-2 A progenitor cells which can be driven to differentiate
      into either oligodendrocytes or type 2-astrocytes depending on the culture
      medium. Indeed, in serum-supplemented medium, human oligodendroglioma cells
      proliferated and expressed the GFAP astrocytic marker. In chemically defined
      medium containing insulin, human oligodendroglioma cells were quiescent and
      expressed the OI oligodendrocyte-specific marker. In both media, human
      oligodendroglioma cells expressed the A2B5 membrane marker as well as the SCIP
      transcription factor specific of 0-2 A cells, further confirming their
      oligodendrocytic origin. Replacement of insulin by platelet-derived growth factor
      (PDGF) and basic fibroblast growth factor (bFGF), known to maintain 0-2 A
      progenitors in a proliferative state, stimulated DNA replication of human
      oligodendroglioma cells cultured in chemically defined medium.

PMID- 8875465
TI  - Cyclin D1 in astrocytic tumours: an immunohistochemical study.
AB  - Forty-eight astrocytic tumours were stained immunohistochemically with antibodies
      to the cell cycle-regulating protein, cyclin D1, and to the proliferation marker
      MIB1 (Ki-67) using formalin fixed paraffin embedded tissue and a microwave
      antigen retrieval system. Cases were classified by the WHO system (1993). The
      labelling indices (LI) for both antibodies were compared with each other and with
      the tumour type. The mean labelling indices for both antibodies increased with
      the degree of malignancy, and a significant difference was seen between the
      pilocytic astrocytoma and diffuse astrocytoma together vs anaplastic astrocytoma
      and glioblastoma together. However, within each tumour type there was
      considerable variation in the labelling indices and a clear cut off value could
      not be demonstrated. There was a strong positive correlation between labelling
      indices for cyclin D1 and MIB1 in diffuse astrocytoma, but this correlation broke
      down increasingly in anaplastic astrocytoma and glioblastoma. There was poor
      correlation between cyclin D1 and MIB1 in pilocytic astrocytoma, a feature which
      appeared to separate them from the diffuse astrocytoma. Average labelling indices
      for cyclin D1 were higher than those of MIB1, which suggests that cyclin D1
      positive cells represent a pool of cells from which proliferation and hence MIB1
      expression can take place. In conclusion, cyclin D1 is overexpressed in
      astrocytic tumours, more so with increasing grade of malignancy and in a way
      which approximately correlates with MIB1 expression.

PMID- 8875466
TI  - Effect of histamine and the H2 antagonist cimetidine on the growth and migration
      of human neoplastic glia.
AB  - Histamine is known to act, at least in part, as a growth factor, as production of
      this neurotransmitter has been found to accelerate the rate of tissue
      proliferation in wound repair, embryogenesis and malignant growth. Histamine
      favours in vivo tumour cell proliferation via H2 receptors. Cimetidine is an H2
      blocker and has been shown to inhibit tumour cell growth. In the present study,
      the growth modulating effects of histamine and cimetidine were assessed on five
      cell lines derived from human brain tumours of different histological types and
      grades of malignancy. Each cell line was treated with either cimetidine or
      histamine for 24 h before kinetic analyses, with PCNA, or motility assays, using
      Transwell migration chambers incorporating a microporous membrane, were carried
      out. Cimetidine significantly inhibited cell proliferation in three out of the
      five cell lines, which may indicate the dependence of proliferation of these cell
      lines on stimulation of the H2 receptor. With regard to migration, it was
      observed that in the majority of cell lines, cimetidine induced migration whilst
      histamine inhibited it. It was concluded that the link between effects of
      histamine on proliferation and its effects on migration must be clarified using a
      larger sample of cell lines.

PMID- 8875467
TI  - Drainage of CSF through lymphatic pathways and arachnoid villi in sheep:
      measurement of 125I-albumin clearance.
AB  - We investigated lymphatic drainage pathways of the central nervous system in
      conscious sheep and quantified the clearance of a cerebrospinal fluid (CSF)
      tracer into lymph and blood. In the first group of studies, 125I-HSA was injected
      into the lateral ventricles of the brain or into lumbar CSF and after 6 h,
      various lymph nodes and tissues were excised and counted for radioactivity.
      Multiple lymphatic drainage pathways of cranial CSF existed in the head and neck
      region defined by elevated 125I-HSA in the retropharyngeal/cervical, thymic, pre
      auricular and submandibular nodes. Implicated in spinal CSF drainage were mainly
      the lumbar and intercostal nodes. In a second group of experiments, multiple
      cervical vessels and the thoracic duct were cannulated and lymph diverted from
      the animals. Transport of tracer through arachnoid villi was taken from
      recoveries in venous blood. Following intraventricular administration, the 6 h
      recoveries of 125I-HSA in the lymph (sum of cervical and thoracic duct) and blood
      were 8.2% +/- 3.0 and 12.5% +/- 4.5 respectively and at 22 h, 25.1% +/- 6.9 and
      20.8% +/- 4.1 respectively. When 125I-HSA was injected into lumbar CSF, the 6 h
      recoveries of tracer in thoracic duct and blood were 11.6% +/- 2.7 and 16.3% +/-
      3.7 respectively. Total lymph and blood recoveries were not significantly
      different in any experiment. We conclude that the clearance of 125I-HSA from the
      CSF is almost equally distributed between lymphatic and arachnoid villi pathways.

PMID- 8875468
TI  - Apolipoprotein E distribution among different plaque types in Alzheimer's
      disease: implications for its role in plaque progression.
AB  - We sought to determine the pattern of ApoE immunoreactivity in mesial temporal
      lobe tissue from 12 Alzheimer patients, age 66-88, and to determine the
      distribution of this immunoreactivity among different plaque types representing
      hypothesized stages of plaque evolution. In these patients, the cortical area of
      ApoE immunoreactivity was 30% that of beta-amyloid. Only 6% of diffuse non
      neuritic amyloid deposits were even weakly ApoE immunoreactive (ApoE+). This is
      in contrast to our previous demonstration that microglia overexpressing
      interleukin-1 (IL-1) are present in most diffuse non-neuritic deposits. Eighty
      three per cent of diffuse neuritic plaques and 86% of dense-core neuritic plaques
      were highly ApoE+, consistent with IL-1-induced astrocyte activation and
      synthesis of ApoE resulting in the appearance of ApoE immunoreactivity in
      neuritic plaques. Dense-core non-neuritic ('burned out') plaques were only rarely
      (6%) ApoE+. These results, together with the known trophic and toxic effects of
      ApoE on neurites, suggest that plaque-associated ApoE contributes to the
      formation of overgrown degenerating (dystrophic) neurites in plaques. However,
      the fact that some neuritic plaques are not ApoE+ suggests contributions by
      additional trophic and toxic factors. Our results are also consistent with a role
      for ApoE in the condensation of diffuse amyloid deposits into a beta-pleated
      sheet form that occurs concomitant with dystrophic neurite formation in the
      neuritic beta-amyloid plaques of Alzheimer's disease.

PMID- 8875469
TI  - Selective alterations in the cellular distribution of apolipoprotein E
      immunoreactivity following transient cerebral ischaemia in the rat.
AB  - The aim of this study was to examine the cellular localization and alterations of
      apolipoprotein E (apoE) following a transient ischaemic insult using
      immunohistochemistry. Transient cerebral ischaemia was induced in Wistar rats by
      occlusion of both carotid arteries with hypotension followed by reperfusion for 4
      h (n = 5), 24 h (n = 5) or 72 h (n = 6). In sham-operated animals (n = 9), the
      carotids were not occluded. In this model, ischaemia for 15 min results in
      selective neuronal damage in the caudate nucleus and neocortex (24 h after
      reperfusion) and the hippocampal CA1 pyramidal cells (72 h after reperfusion)
      while there is minimal damage in other areas such as the CA3 hippocampal region.
      In sham animals apoE immunoreactivity was confined to astrocytes and their
      processes. ApoE immunoreactivity was not altered at 4 h post-ischemic
      reperfusion. At 24 h reperfusion, intense apoE staining of the cytoplasm of
      astrocytes and neuropil within the caudate and neocortex was observed and at 72 h
      reperfusion apoE stained neuronal cell bodies within these regions. Within the
      CA1 region at 24 h reperfusion, there was increased immunoreactivity of the
      cytoplasm of astrocytes and the neuropil was more intensely stained compared with
      sham animals. At 72 h reperfusion, intense apoE staining of pyramidal cell bodies
      and dendrites was consistently observed in the CA1 region of the hippocampus. In
      contrast, at 72 h reperfusion, apoE staining of astrocytic processes was
      dramatically reduced in the CA1 region although GFAP staining indicated their
      preservation. The results demonstrate that following an ischaemic insult apoE is
      localized to degenerating neurons and their processes. This may indicate an
      inherent protective response of cells to injury. Alternatively, the results are
      consistent with the hypothesis that apoE is synthesized and released by
      astrocytes and taken up by neurons following injury.

PMID- 8875470
TI  - Hyperbaric oxygenation prevents delayed neuronal death following transient
      ischaemia in the gerbil hippocampus.
AB  - The mechanism of the neuroprotective effect of hyperbaric oxygenation remains
      unclear although its clinical benefits have been well recognized for human
      ischaemic neuronal disease. The preventive effect of hyperbaric oxygenation
      against delayed neuronal death was investigated in the gerbil following transient
      forebrain ischaemia. Delayed neuronal death in the gerbil was produced by clips
      on both the common carotid arteries (10 min). Morphological examination was
      carried out after several protocols of hyperbaric oxygenation, modified from the
      protocols for human ischaemic neuronal disease. Neurons in the hippocampal CA1
      were well preserved in the gerbils treated with hyperbaric oxygenation, more so
      than in the gerbils with no hyperbaric oxygenation. Moreover, more neurons were
      preserved in the CA1 treated with hyperbaric oxygenation within 6 h of the
      ischaemia, than when the hyperbaric oxygenation was started 24 h after the
      ischaemia. The induction of heat shock proteins (HSP72 and HSP27) became weaker
      in the gerbils with hyperbaric oxygenation than in those without hyperbaric
      oxygenation, as seen immunohistochemically. We also observed an increase in dense
      bodies, that were shown to be lysosomes and myelinoid structures in the cytoplasm
      of the neurons ultrastructurally, in the hippocampus with hyperbaric oxygenation.
      However, no oxygen toxicity to the neurons was detected, up to at least two
      atmospheres absolute. This experimental system was useful to investigate the
      preventive mechanism of hyperbaric oxygenation against delayed neuronal death in
      the gerbil, and to determine the clinical indications and the most effective
      protocol for hyperbaric oxygenation for ischaemic neuronal damage in the human
      brain.

PMID- 8875471
TI  - Differentiation of Purkinje cells in cerebellar slice cultures: an
      immunocytochemical and Golgi EM study.
AB  - In the rat central nervous system, the cerebellar cortex has a stereotypical
      cytoarchitecture and a characteristic connectivity pattern, both mainly formed
      post-natally. Organotypic cultures of immature cerebellar tissue were used to
      study the formation of the cerebellar lamination and the differentiation of
      Purkinje cells in the absence of their extracerebellar afferents. The lamination
      was retained in the majority of the cerebellar cultures and most Purkinje cells
      were aligned. Axonal profiles of Purkinje cells, immunolabelled for UCHT1 or anti
      calbindin D-28 k, followed pathways similar to those in vivo cerebellum. The
      dendrites were orientated towards the superficial layer except of those neurons
      which were ectopically positioned. Unlike in vivo, the dendritic arborization of
      Golgi-impregnated/gold-toned or immunostained Purkinje cells was reduced and the
      dendritic spines were often elongated. Somatic spines, a morphological feature of
      immature Purkinje cells persisted even after 4 weeks in culture. We conclude that
      the Purkinje cells in organotypic cultures send their axon to the correct target
      region independent of their local position. In contrast, the dendritic
      orientation and differentiation is influenced by the cellular environment and by
      specific synaptic interaction.

PMID- 8875472
TI  - Perimesencephalic nonaneurysmal subarachnoid hemorrhage: review of the
      literature.
AB  - OBJECTIVE: A critical review of the literature on the incidence, presentation,
      diagnosis, and prognosis of perimesencephalic nonaneurysmal subarachnoid
      hemorrhage. METHODS: Review of the relevant literature. CONCLUSION: The
      importance of early computed tomography (< 3 d), anatomy of the perimesencephalic
      and neighboring cisterns, and adequate four-vessel angiography are discussed.
      Treatment strategies, including the avoidance of repeated angiographic studies
      and surgical exploration, are presented.

PMID- 8875473
TI  - Clinical grading and outcome after early surgery in aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: We propose a modification to the currently prevailing grading systems
      in patients with subarachnoid hemorrhage. The changes will make them correlate
      more strongly with the surgical results. METHODS: The relationship between
      preoperative clinical grades and management outcome was retrospectively
      investigated in a series of 304 patients with ruptured cerebral aneurysms on the
      anterior circle of Willis. Preoperatively, every patient was evaluated with the
      Hunt and Kosnik grading system, the World Federation of Neurological Surgeons
      Scale, and the Glasgow Coma Scale. All the patients underwent surgical treatment
      on the aneurysms within 72 hours of the first onset of symptoms. Hyperdynamic
      therapy was performed after the surgery was evaluated with the Glasgow Outcome
      Scale. RESULTS: In the Hunt and Kosnik system, the outcome was significantly
      different between the patients with Grades II and III and those with Grades III
      and IV, but there was no significant difference among the adjacent grades except
      between patients with Glasgow Coma Scale scores of 13 and 14. The outcome of
      oriented patients was significantly better than that of confused patients.
      Neither eye opening nor presence of focal deficit was a significant prognostic
      factor. CONCLUSION: To grade patients with subarachnoid hemorrhage objectively,
      three responses should be recorded separately in the Glasgow Coma Scale score.
      Patients with confused verbal responses should be graded lower than those who are
      oriented, even when they have the same total score.

PMID- 8875474
TI  - Embolization of cerebral arteriovenous malformations: Part I--Technique,
      morphology, and complications.
AB  - OBJECTIVE: The aim of this two-part study is to give a full account of all
      patients referred for embolization of arteriovenous malformations (AVMs) from
      1987 to 1993. This article (Part I of II) presents the patient study, including
      angiographic features and their relation to the immediate outcome of
      embolization. METHODS: Of the 192 patients referred, 150 were subsequently
      treated. Most patients were referred by neurosurgeons, and 85% of the AVMs were
      Spetzler-Martin Grade > or = 3. We have accounted for the 42 patients who did not
      undergo embolization. RESULTS: Occlusion from embolization alone (total
      embolization) was obtained in 13% of patients. Full treatment (total embolization
      or embolization and then stereotactic radiation or surgery) was achieved in two
      thirds of all patients (n = 100, 66%), and combined treatment with stereotactic
      gamma radiation was the most important part of the treatment strategy. The
      procedural mortality was 1.3%. The total incidence of complications after
      embolization was high (40%), but only 6.7% of cases were labeled severe. Of all
      angiographic features that were considered, large size and the presence of deep
      feeders were predictors of failure to achieve full treatment. Thirty-four
      patients with AVMs < 8 cc were included in the study. These could have been
      irradiated as the sole treatment. In this group of small AVMs, the results of
      embolization were far better than in the whole group. Fourteen of the AVMs had
      volumes of < 4 cc, and 10 of these (71%) were totally embolized. One patient had
      a hemianopsia. Among AVMs 4 to 8 cc in volume (n = 20), the total embolization
      rate was 15%, the full treatment rate in combination with gamma treatment was
      75%, and 10% of the patients were operated on after embolization. Severe
      complications occurred in 15% of patients, but no complications occurred after
      November 1990. CONCLUSION: In a series of AVMs, most of which were regarded as
      unsuitable for surgical excision, two-thirds were reduced to a size suitable for
      gamma knife treatment or totally occluded by embolization alone. The total
      complication rate was high, but the combined rate of death and complications
      affecting lifestyle was 8.0%, equal to approximately 3.2 years of natural
      history.

PMID- 8875475
TI  - Embolization of cerebral arteriovenous malformations: Part II--Aspects of
      complications and late outcome.
AB  - OBJECTIVE: From 1987 through 1993, we performed embolizations on 150 patients
      with cerebral arteriovenous malformations (AVMs) at Sahlgrenska University
      Hospital. The patients ranged in age from 5 to 70 years (35.5 +/- 14.8 yr, mean
      +/- standard deviation) and were selected by neurosurgeons in Scandinavia. We
      analyzed the risk of complications and late outcome to have a better basis for
      the decision to perform embolization. METHODS: The follow-up was a personal
      clinical examination of all surviving patients by a neurologist. Files for all
      patients were also studied. RESULTS: In 34 patients, the AVMs were eliminated by
      embolization alone (20 patients) or by supplementary surgery (14 patients). In 66
      patients, the AVMs were embolized to a size suitable for supplementary
      stereotactic radiation. The clinical course was stable for those 100 patients.
      Another group of 50 patients who had undergone embolization was only partially
      treated, and as a group, those patients had less favorable outcomes. The
      manifestations or symptoms leading to diagnosis were in concordance with other
      studies. Headache and epilepsy showed a positive response to treatment in
      patients whose AVMs had been eliminated as well as in those who received only
      partial treatment. A history of cerebral bleeding did not influence the prognosis
      of recurrent bleeding. Conversely, AVMs with feeder or nidus aneurysms were
      related to an increased risk of bleeding. If there was a history of bleeding in a
      patient with large, partially treated AVMs, the prognosis for survival was
      diminished. CONCLUSION: The indication for treatment increases with the
      occurrence of AVMs with associated aneurysms. For patients with large AVMs, a
      history of bleeding justifies a more aggressive approach to treatment. The
      reduced risk of complications during the last years of the study also increases
      the indication for embolization.

PMID- 8875477
TI  - A phase I study of an anti-epidermal growth factor receptor monoclonal antibody
      for the treatment of malignant gliomas.
AB  - OBJECTIVE: Epidermal growth factor receptor (EGFR) is an operationally specific
      antigen in malignant gliomas; it is overexpressed in > 60% of these tumors,
      whereas its expression is very low in normal brain. This study aimed to evaluate
      whether an adequate amount of an anti-EGFR monoclonal antibody (MAb) could reach
      a tumor after a single intravenous administration. METHODS: This study was open,
      nonrandomized, and uncontrolled. Single doses (20, 40, 100, 200, or 400 mg) of
      the murine MAb EMD55900 (MAb 425) were administered intravenously before surgery
      to 30 patients with malignant brain tumors. Serum samples were taken at defined
      time intervals during infusion, to determine EMD55900 concentrations, and 10, 21,
      and/or 42 days after infusion, to evaluate the development of human anti-mouse
      antibodies. Tumor samples were investigated for EGFR and EMD55900 contents.
      RESULTS: Tolerance to EMD55900 was good. Increased liver transaminase levels were
      noted for three patients with Grade 1 toxicity. Twenty patients developed
      significant human anti-mouse antibody titers, without correlation with the
      administered dose. The median half-life of EMD55900 in serum ranged from 6 hours
      for 20 mg to 24 hours for 400 mg. In the membrane fractions of the tumors, EGFR
      saturation by EMD55900 varied with the injected dose of MAb. No binding was
      detected after a 20-mg dose. After doses of 40, 100, 200, and 400 mg, the mean
      saturation levels were 33, 73, 89, and 71%, respectively. CONCLUSION: This study
      indicates that a single intravenous administration of EMD55900 is well tolerated
      and produces substantial in vivo tumor binding with doses > 100 mg.

PMID- 8875476
TI  - Prognostic value positron emission tomography with [18F]fluoro-2-deoxy-D-glucose
      in the low-grade glioma.
AB  - OBJECTIVE: The natural history of the supratentorial low-grade glioma (LGG) of
      the adult is variable, and its malignant transformation is hardly predictable.
      Because positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG) has
      prognostic value in high-grade gliomas, this study was designed to search for a
      possible relationship between glucose metabolism and risk of malignant evolution
      in LGGs. METHODS: Positron emission tomography with FDG was performed in 28
      patients with LGGs (22 at the time of diagnosis and 6 after the diagnosis). A
      metabolic grading system based on the visual inspection of the positron emission
      tomographic images was used. RESULTS: In 19 patients, no area of FDG uptake
      higher than in the white matter was detected (metabolic Grade 1). All of those
      patients were alive at the end of the follow-up period. Only one of the patients
      presented a histological modification 7 months after the diagnosis. Nine patients
      presented areas of increased FDG uptake (metabolic Grade 2 or 3). Those areas
      were found in the tumor area in eight patients and in an area of radionecrosis in
      one. Of the nine patients with FDG "hot spots," six died, two had recurrence but
      were alive at the end of the follow-up period, and the patient with radionecrosis
      had no signs of recurrence. CONCLUSIONS: The presence of areas of increased FDG
      uptake in a histologically proven LGG predicts, in most cases, a deleterious
      evolution. This metabolic feature, detectable with a noninvasive procedure, may
      provide a clue to cellular changes, announcing malignant transformation in a
      tumor that retains the histological features of an LGG. Protocols with aggressive
      therapeutic strategies in this situation should be considered for evaluation.

PMID- 8875478
TI  - Transnasal microsurgery in children and adolescents with Cushing's disease.
AB  - OBJECTIVE: Transnasal adenomectomy is the treatment of choice for Cushing's
      disease. We review the diagnostic peculiarities, specific surgical problems, and
      outcome of children and adolescents with Cushing's disease. METHODS: We report on
      our series of 55 consecutive children and adolescents (range, 4.2-18.9 yr [mean
      age, 14.4 yr]; female:male = 1.1:1.0; mean follow-up, 54.5 +/- 38.6 mo [standard
      deviation]) with Cushing's disease on whom we performed surgery since 1980. The
      indication for transsphenoidal surgery is based on endocrinological parameters
      and not on neuroradiological findings. RESULTS: Detection rate of the tumor site
      was 22% using computed tomography and 33% using magnetic resonance imaging. Only
      7 of 13 interpetrosal adrenocorticotropic hormone gradients obtained during
      inferior petrosal sinus sampling correctly lateralized the tumor site
      preoperatively (53.8%). In cases of incomplete sphenoid pneumatization, adequate
      exposure is achieved by drilling. The tumor finding rate is 98%. The remission
      rate is 100% when two early subsequent operations are included. The recurrence
      rate for 45 primary operations with follow-up of at least 1 year is 15.5%. Seven
      of nine subsequent operations for recurrent hypercortisolism were successful. One
      patient needed three more operations until hypercortisolism subsided; one patient
      achieved remission after additional pituitary irradiation. The surgical morbidity
      was low in this series, which consisted of two cerebrospinal fluid fistulas. The
      incidence of hypopituitarism after primary operations (10.3%) is significantly
      lower than after subsequent operations (45.5%). CONCLUSION: Direct transnasal
      submucosal surgery for Cushing's disease is successful, and pituitary function
      can be preserved in most of these young patients.

PMID- 8875479
TI  - Operative treatment of spontaneous spinal epidural hematomas: a study of the
      factors determining postoperative outcome.
AB  - OBJECTIVE: We clarify the factors affecting postoperative outcomes in patients
      who have suffered spontaneous spinal epidural hematomas. METHODS: We review 330
      cases of spontaneous spinal epidural hematomas from the international literature
      and three unpublished cases of our own. Attention was focused on sex, age,
      medical history, mortality, size and position of the hematoma, vertebral level of
      the hematoma, preoperative neurological condition, operative interval, and
      postoperative result. RESULTS: Sex, age, and size and position of the hematoma
      did not correlate with postoperative outcome. Mortality correlated highly with
      cervical or cervicothoracic hematomas, especially in patients with cardiovascular
      disease and those undergoing anticoagulant therapy. Incomplete preoperative
      sensorimotor deficit correlated highly with favorable outcomes (P < 0.0005), and
      recovery was significantly better when decompression was performed in < or = 36
      hours in patients with complete sensorimotor loss (P < 0.05) and in < or = 48
      hours in patients with incomplete sensorimotor deficit (P < 0.005). CONCLUSION:
      The critical factors for recovery after spontaneous spinal epidural hematoma are
      the level of preoperative neurological deficit and the operative interval. The
      vertebral level of the hematoma did not correlate with postoperative results,
      which suggests that local compression, rather than vascular obstruction, is the
      main factor in producing neurological deficit.

PMID- 8875480
TI  - Neuropsychological functioning and recovery after mild head injury in collegiate
      athletes.
AB  - OBJECTIVE: This study prospectively examined neuropsychological functioning in
      2300 collegiate football players from 10 National Collegiate Athletic Association
      Division A universities. The study was designed to determine the presence and
      duration of neuropsychological symptoms after mild head injury. METHODS: A
      nonequivalent repeated measures control group design was used to compare the
      neuropsychological test scores and symptoms of injured players (n = 183) with
      those of gender, age, and education matched controls. A number of
      neuropsychological tests, including the Paced Auditory Serial Addition Test, the
      Digit Symbol Test, and the Trail Making Test, as well as a symptom checklist were
      used. TECHNIQUE: Players and controls were assessed before engaging in game
      activity and 24 hours, 5 days, and 10 days after injury, using the standardized
      test battery and symptom checklist. RESULTS: Players with head injuries displayed
      impaired performance and increased symptoms in comparison to controls, but this
      impairment resolved within 5 days in most players. Players with head injuries
      showed significant improvement between 24 hours and 5 days, as well as between 5
      and 10 days. CONCLUSION: Although single, uncomplicated mild head injuries do
      cause limited neuropsychological impairment, injured players generally experience
      rapid resolution of symptoms with minimal prolonged sequelae.

PMID- 8875481
TI  - Functional magnetic resonance imaging mapping of the motor cortex in patients
      with cerebral tumors.
AB  - OBJECTIVE: The purpose of this study was to determine the usefulness of
      functional magnetic resonance imaging (FMRI) to map cerebral functions in
      patients with frontal or parietal tumors. METHODS: Charts and images of patients
      with cerebral tumors or vascular malformations who underwent FMRI with an
      echoplanar technique were reviewed. The FMRI maps of motor (11 patients), tactile
      sensory (12 patients), and language tasks (4 patients) were obtained. The
      location of the FMRI activation and the positive responses to intraoperative
      cortical stimulation were compared. The reliability of the paradigms for mapping
      the rolandic cortex was evaluated. RESULTS: Rolandic cortex was activated by
      tactile tasks in all 12 patients and by motor tasks in 10 of 11 patients.
      Language tasks elicited activation in each of the four patients. Activation was
      obtained within edematous brain and adjacent to tumors. FMRI in three cases with
      intraoperative electrocortical mapping results showed activation for a language,
      tactile, or motor task within the same gyrus in which stimulation elicited a
      related motor, sensory, or language function. In patients with > 2 cm between the
      margin of the tumor, as revealed by magnetic resonance imaging, and the
      activation, no decline in motor function occurred from surgical resection.
      CONCLUSIONS: FMRI of tactile, motor, and language tasks is feasible in patients
      with cerebral tumors. FMRI shows promise as a means of determining the risk of a
      postoperative motor deficit from surgical resection of frontal or parietal
      tumors.

PMID- 8875482
TI  - Use of lumbar periosteal turnover flaps in myelomeningocele closure.
AB  - OBJECTIVE: We report our experience with a previously undescribed method of
      myelomeningocele closure, which is the use of bilateral lumbar periosteal flaps
      as an additional tissue layer in complex cases. These flaps reinforce the dural
      repair, act to protect the spinal cord, and may help to contain any potential
      cerebrospinal fluid leak from the primary repair of the cord, thereby preventing
      pseudomeningocele formation. METHODS: The repair involves the development of
      bilateral thoracolumbar fascial flaps in conjunction with periosteal flaps, which
      are elevated from adjacent lumbar pedicles and transverse processes, thus forming
      a composite tissue flap. These periosteally based flaps may be closed in a "pants
      over vest" fashion to completely cover the spinal defect, reinforcing the
      neurosurgical repair. The flap anatomy and dissection are detailed. RESULTS: Two
      representative cases in which the lumbar periosteal turnover flap procedure was
      used are reported. One patient was operated on during the early neonatal period
      for primary myelomeningocele repair; the other was operated on at age 5 years
      after a tethered cord release. Durable, stable soft tissue coverage of the spinal
      cord was obtained in both patients, with a postoperative follow-up period of at
      least 12 months. There was no recurrence of the pseudomeningocele noted
      preoperatively in the second patient. CONCLUSION: The lumbar periosteal turnover
      flap may be used to reinforce tenuous spinal cord and dural repairs in the
      myelomeningocele patient. This method provides a secure and watertight closure
      over the primary repair of the cord, may help to contain potential cerebrospinal
      fluid leaks, and adds an additional autologous tissue layer to standard skin or
      muscle flap repairs.

PMID- 8875483
TI  - Meningeal architecture of the cavernous sinus: clinical and surgical
      implications.
AB  - OBJECTIVE: The meningeal structure of the cavernous sinus (lateral sellar
      compartment) was anatomically and histologically studied. We discuss the clinical
      and surgical significance and present clinical examples of cranial base tumors.
      METHODS: Ten adult cadaveric heads were used for microsurgical dissection or
      histological studies. Specimens of the cavernous sinus were continuously
      sectioned in three dimensions and stained by Masson's trichrome method. The
      findings are anatomically discussed as they pertain to presented clinical cases.
      RESULTS: The cavernous sinus, located in an interdural space between periosteal
      and meningeal dura, is properly accessed by detachment of the periosteal bridge
      between the superior orbital fissure and the middle fossa. The lateral meningeal
      dura is dissected under minimal hemorrhage from the sinus, with a surgically
      important cleaving plane between the "deep layer," a semitransparent meningeal
      sheath with which the cranial nerves are covered and protected. It has various
      degrees of meningeal pockets, of which Meckel's cave is the largest example.
      Adventitia of the carotid artery in the sinus, uncovered with protective
      meninges, is considered to contact directly with tumors of the sinus origin. The
      meningeal wall of the cavernous sinus anatomically has three weak points as far
      as tumor invasion and extension are concerned: the venous plexus around the
      superior orbital fissure, the loose texture of the medial wall around the
      pituitary body, and dural pockets of the IIIrd and Vth cranial nerves. The dural
      wall is extremely thin or missing at those points. CONCLUSION: A surgical
      technique based on the meningeal anatomy is important for cavernous sinus
      surgery. The cavernous apex and Meckel's cave, which are spaces of convergence of
      cranial nerves, however, are weak points for surgical dissection. The presence or
      absence of tumor invasion into those areas may influence the microsurgical
      results.

PMID- 8875485
TI  - Molecular methods of enhancing lumbar spine fusion.
AB  - OBJECTIVE: An optimal method for spinal fusion would induce rapid growth of bone
      via an osteoconductive and osteoinductive implant. This study examines the spinal
      fusion enhancement potential of some osteoconductive and osteoinductive
      biomaterials. METHODS: Four similar canines received unilateral posterolateral
      fusions on the left side at T13-L1 and L4-L5 and on the right side at L2-L3 and
      L6-L7. The experiments were grouped as follows: Group A, autogenous bone
      harvested from the iliac crest; Group B, autogenous bone and collagen; Group C,
      no implant; and Group D, autogenous bone, collagen, and recombinant human bone
      morphogenetic protein-2. Radiographic assessment, three-dimensional computed
      tomographic volumetric analysis, and biomechanical testing were performed at each
      level. RESULTS: For Groups A and B, the fusions demonstrated moderate bone
      formation at 6 and 12 weeks postoperatively. Group D fusions exhibited earlier
      and more dramatic increases in volume and radiodensity and eventually were
      comparable in size to the vertebral bodies. Average fusion volumes computed from
      three-dimensional computed tomographic analysis were: Group A = 1.243 cc, Group B
      = 0.900 cc, Group C = 0.000 cc, and Group D = 6.668 cc (P = 0.003 compared to
      Group A). Group D exhibited flexion and extension biomechanical properties much
      greater than controls. The addition of recombinant human bone morphogenetic
      protein-2 consistently yielded the strongest fused segments and, on average,
      enhanced extension stiffness by 626% and flexion stiffness by 1120% over
      controls. CONCLUSION: The most advantageous spinal fusion implant matrix
      consisted of recombinant human bone morphogenetic protein-2, autogenous bone, and
      collagen. Future investigators, however, need to examine the appropriate
      quantities of the individual components and clarify the efficacy of the matrix
      for the various types of spinal fusion approaches.

PMID- 8875484
TI  - Expression of angiogenesis factors and selected vascular wall matrix proteins in
      intracranial saccular aneurysms.
AB  - OBJECTIVE: Little is known about the biological mechanisms associated with the
      genesis, growth, and rupture of intracranial saccular aneurysms. It is postulated
      that the vascular wall pathological response of aneurysmal disease is associated
      with abnormal angiogenesis factor expression. METHODS: We have examined the
      expression and distribution of immunoreactivity to angiogenesis growth factors
      (vascular endothelial growth factor and basic fibroblast growth factor) and
      selected vascular wall matrix proteins (fibronectin, Type IV collagen, and alpha
      smooth muscle actin) in the walls of human intracranial aneurysms from surgical
      biopsy or autopsy specimens. Double antibody immunohistochemical stains were
      performed in contiguous fixed sections from three control circle of Willis
      arteries, five berry aneurysms, four giant aneurysms, and one mycotic aneurysm
      (three unruptured and seven ruptured lesions). RESULTS: The aneurysmal wall
      exhibited diffuse disorganized expression of matrix proteins as compared to their
      organization in control vessels. There was strong patchy expression of vascular
      endothelial growth factor within the walls of all aneurysms, including marked
      staining of capillaries and small vessels within the thickened walls of giant
      lesions. The expression of basic fibroblast growth factor was more diffuse and
      occurred around the fibrocytes and myocytes within the disrupted media of 9 of 10
      aneurysms. CONCLUSIONS: These results confirm the gross architectural molecular
      disruption in the walls of intracranial aneurysms and illustrate an apparent
      biological response involving angiogenesis factors. Further research should
      elucidate the time course and possible causal relationships of these changes to
      aneurysm growth and rupture with the aim of possible therapeutic manipulation.

PMID- 8875486
TI  - The fetal spinal cord does not regenerate after in utero transection in a large
      mammalian model.
AB  - OBJECTIVE: Regeneration and functional recovery after spinal cord transection do
      not occur in mammalian animals and humans postnatally. The goal of this study was
      to test whether in utero transection of the fetal spinal cord is succeeded by
      anatomic healing and functional recovery. METHODS: In five sheep fetuses, at 60
      days of gestation and 75 days of gestation (term = 150 d), the spinal cord was
      completely transected at T10. The animals were delivered near term by cesarean
      section for clinical evaluation, measurement of cortical somatosensory evoked
      potentials, and morphological assessment. RESULTS: The newborn lambs demonstrated
      sensory-motor paraplegia, were incontinent of urine and stool, and exhibited a
      spinally generated, ambulatory pattern of the hindlimbs. No cortical
      somatosensory evoked potentials could be recorded in response to posterior tibial
      nerve stimulation, although potentials from the ulnar nerve, which enters the
      cord rostral to the lesion, were normal in all animals. Histologically, no
      neuronal connections across the transection site were identified. The cord
      proximal to the lesion was grossly normal, whereas distal to the transection, it
      appeared slightly smaller but with the cytoarchitecture preserved. CONCLUSIONS:
      Unlike in lower vertebrate and avian species, the fetal ovine spinal cord has no
      detectable spontaneous regenerative capabilities when transected during
      midgestation. Gap formation after transection, secondary posttraumatic cell
      death, and missing guiding channels for sprouting axons may be factors involved
      in the absence of any regenerative response.

PMID- 8875487
TI  - Changes in endothelial nitric oxide synthase mRNA during vasospasm after
      subarachnoid hemorrhage in monkeys.
AB  - OBJECTIVE: We attempt to determine whether changes in messenger ribonucleic acid
      (mRNA) for nitric oxide synthase (NOS) and soluble guanylate cyclase, enzymes
      that mediate endothelium-dependent vasodilation in cerebral arteries, occur after
      subarachnoid hemorrhage (SAH) in monkeys. METHODS: Baseline cerebral angiograms
      were obtained, and right-sided SAH was induced by microsurgically placing
      autologous blood clot against the right anterior circle of Willis in seven
      monkeys. Seven days later, angiographic studies were repeated and the animals
      were killed. Right (vasospastic) and left (control) middle cerebral arteries and
      underlying cortex were removed. The competitive reverse transcriptase polymerase
      chain reaction was used to quantify mRNA for soluble guanylate cyclase and two
      isoforms of constitutive NOS in these tissues. RESULTS: Comparison of angiograms
      at baseline and after 7 days showed a 41 +/- 7% (mean +/- standard error of the
      mean, P < 0.05, Wilcoxon test) decrease in diameter of the right middle cerebral
      artery. After the animals were killed, comparison of right and left middle
      cerebral arteries showed a 56 +/- 11% decrease (P < 0.005, paired t test) in
      endothelial NOS mRNA. There was a 142 +/- 39% (P < 0.05) increase in right cortex
      endothelial NOS mRNA compared to the left cortex. There were no significant
      differences between right and left sides in mRNAs for soluble guanylate cyclase
      or brain NOS. CONCLUSION: Decreased endothelial NOS mRNA in cerebral arteries 7
      days after SAH may be caused by endothelial cell damage and could contribute to
      vasospasm after SAH. Increased endothelial NOS in brain tissue may reflect a
      compensatory vasodilator mechanism of the brain against the cerebral ischemia
      associated with vasospasm and SAH.

PMID- 8875488
TI  - Relationship between protein kinase C and adenylyl cyclase activity in the
      regulation of growth hormone secretion by human pituitary somatotrophinomas.
AB  - OBJECTIVE: To determine the potential role of protein kinase C (PKC) and its
      relationship to adenylyl cyclase activity in controlling growth hormone (GH)
      secretion by human pituitary somatotrophinomas. METHODS: Twenty-eight
      somatotrophinomas were placed into cell culture, and the in vitro effects of the
      PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA) and the PKC inhibitor
      staurosporine on basal and GH-releasing hormone (GHRH)-stimulated GH secretion
      were examined. In addition, the influence of chronic exposure of cultured
      somatotrophinoma cells to TPA on the rate of inositol 1,4,5-trisphosphate
      production was determined. Each tumor was assessed for the presence of gsp
      oncogenes, and thus constitutive adenylyl cyclase activity, by direct sequence
      analysis of polymerase chain reaction-generated deoxyribonucleic acid. GH
      secretory responses of tumors with and without these oncogenes were compared.
      RESULTS: TPA consistently stimulated GH secretion by cultured somatotrophinoma
      cells. There was no difference in response between somatotrophinomas with and
      without gsp oncogenes, and the effects did not correlate with the variable
      stimulation exerted by GHRH. Tumors in which GHRH had no significant effect
      nevertheless responded to TPA. In combination, TPA and GHRH exerted additive
      stimulation. TPA treatment of cultured somatotrophinoma cells eventually resulted
      in suppression of inositol 1,4,5-trisphosphate production, probably reflecting
      down-regulation of membrane phosphatidylinositol hydrolysis, a second messenger
      system that also generates the endogenous PKC activator diacylglycerol. GHRH had
      no effect on phosphatidylinositol hydrolysis. In contrast to the effects of TPA,
      the PKC inhibitor staurosporine tended to reduce GH secretion, although this
      effect was not observed in all tumors examined. As with TPA, the effects of
      staurosporine did not correlate with presence or absence of gsp oncogenes.
      Furthermore, staurosporine did not reduce the stimulatory effects exerted by GHRH
      on GH secretion. CONCLUSION: These results demonstrate a role for the
      phosphatidylinositol-PKC second messenger cascade in controlling GH secretion by
      human pituitary somatotrophinomas. The results also show that the system operates
      relatively independent of intracellular adenylyl cyclase and, thus, protein
      kinase A.

PMID- 8875490
TI  - Neurological surgery at the University of Vienna.
AB  - ANTON VON EISELSBERG was the first to resect a cerebral tumor at the First
      Surgical Clinic at the General Hospital in Vienna in 1904. He successfully
      removed a cerebral glioma, the first of no fewer than 15,000 tumors operated on
      at that hospital to date. von Eiselsberg and his successors, Egon Ranzi and
      Leopold Schonbauer, as heads of the First Surgical Clinic, devoted themselves
      intensively to brain surgery, and neurosurgery developed to be an integral part
      of Viennese surgery. During the first decades, a prominent neurologist, Otto
      Marburg, and a world-famous anatomist, Julius Tandler, were members of the
      neurosurgical operating team. This approach changed in the 1950s, when the brain
      surgeons aimed at becoming independent of the basic sciences. The founding of an
      independent neurosurgical department at the University of Vienna in 1964 under
      Herbert Kraus also marked the beginning of the formation of specialized sections
      for pediatric and stereotactic neurosurgery. After 1968, the operating microscope
      was greatly emphasized. As of 1970, cerebral tumors and cerebrovascular lesions
      were treated microneurosurgically. Many operations were performed by surgeons who
      were experienced in neurosurgery. This again changed in 1978 under the new head
      of the department, Wolfgang Koos, who regarded the neurosciences as the basis for
      neurosurgical training as well as neurosurgical activity. The reorganization of
      the neurosurgical institution coincided with the construction of a large modern
      building with state-of-the-art equipment for microneurosurgery, radiosurgery
      (gamma knife), neurodiagnostics, laboratories, etc. Many details of the
      construction plans, the equipment, and the organization of the department have
      their roots in the years that the present head of the department spent in the
      United States; this is also the reason for the close connection and cooperation
      of Vienna neurosurgery with many neurosurgeons in the United States.

PMID- 8875489
TI  - Isolated cerebral hypothermia by single carotid artery perfusion of
      extracorporeally cooled blood in baboons.
AB  - OBJECTIVE: Hypothermia has been demonstrated to protect the brain from ischemic
      or traumatic injury. Previous efforts to induce cerebral hypothermia have relied
      on techniques requiring total body cooling that have resulted in serious
      cardiovascular derangements. A technique to selectively cool the brain, without
      systemic hypothermia, may have applications for the treatment of neurological
      disease. METHODS: After induction of general anesthesia in 12 baboons, the right
      common carotid artery and ipsilateral femoral artery were each occlusively
      cannulated and joined to a centrifugal pump. In a closed-circuit system, blood
      was continually withdrawn from the femoral artery, cooled by water bath, and
      infused through the common carotid artery with its external branches occluded.
      Pump flow was varied so that right carotid pressure approximated systemic blood
      pressure. In six animals, perfusate was cooled to decrease right cerebral
      temperature to < 19 degrees C for 30 minutes. In six animals, right cerebral
      temperature was decreased to < 25 degrees C for 3 hours. In those six animals,
      133Xe was injected into the right carotid artery before, during, and after
      hypothermia. Peak radioactivity and washout curves were recorded from bilateral
      cranial detectors. Systemic warming was accomplished by convective air and warm
      water blankets. Esophageal, rectal, and bilateral cerebral temperatures were
      continuously recorded. RESULTS: In animals cooled to < 19 degrees C, right
      cerebral temperature decreased from 34 degrees C to 18.5 +/- 1.1 degrees C (mean
      +/- standard deviation), P < 0.01, in 26 +/- 13 minutes. Simultaneously, left
      cerebral temperature decreased to 20.7 +/- 1.6 degrees C. During 30 minutes of
      stable cerebral hypothermia, esophageal temperature decreased from 35.1 +/- 2.3
      degrees C to 34.2 +/- 2.2 degrees C, P < 0.05. In animals cooled to < 25 degrees
      C, right cerebral temperature decreased from 34 degrees C to 24.5 +/- 0.6 degrees
      C in 12.0 +/- 6.0 minutes, P < 0.01. Simultaneously, left cerebral temperature
      decreased to 26.3 +/- 4.8 degrees C. After 3 hours of stable cerebral
      hypothermia, esophageal temperature was 34.4 +/- 0.5 degrees C, P < 0.05. Right
      hemispheric cerebral blood flow decreased during hypothermia (26 +/- 16
      ml/min/100 g) compared to values before and after hypothermia (63 +/- 29 and 51
      +/- 34 ml/min/100 g, respectively; P < 0.05). Furthermore, hypothermic perfusion
      resulted in a proportionally increased radioactivity peak detected in the left
      cerebral hemisphere after right carotid artery injection of 133Xe (0.8 +/- 0.2:1,
      left:right) compared to normothermia before and after hypothermia (0.3 +/- 2 and
      0.3 +/- 1, respectively; P < 0.05). Normal heart rhythm, systemic arterial blood
      pressure, and arterial blood gas values were preserved during hypothermia in all
      animals. CONCLUSION: Bilateral cerebral deep or moderate hypothermia can be
      induced by selective perfusion of a single internal carotid artery, with minimal
      systemic cooling and without cardiovascular instability. This global brain
      hypothermia results from profoundly altered collateral cerebral circulation
      during artificial hypothermic perfusion. This technique may have clinical
      applications for neurosurgery, stroke, or traumatic brain injury.

PMID- 8875491
TI  - A mucopyocele of the clivus: case report.
AB  - OBJECTIVE AND IMPORTANCE: There are increasing reports of nasal sinus
      mucopyoceles eroding the base of the cranium and causing the rapid onset of
      neurological complications. Uncommon presentations can mimic tumors, but the
      infectious nature mandates an urgent surgical decompression. It is important to
      document these uncommon presentations. CLINICIAL PRESENTATION: A mucopyocele of
      the clivus is reported in a patient with a frequent history of sinusitis.
      Diplopia caused by an acute sixth nerve palsy prompted the radiological diagnosis
      with computed tomography and magnetic resonance imaging. INTERVENTION:
      Transsphenoidal drainage of the lesion lead to marked improvement in the patient.
      CONCLUSION: This is the third reported case of a clival mucocele. Mucoceles of
      nasal sinuses can erode intracranially, causing neurological sequalae, and clival
      involvement is extremely rare. Early drainage leads to marked improvement.

PMID- 8875492
TI  - Xanthogranuloma with massive hematoma in the third ventricle: case report.
AB  - OBJECTIVE AND IMPORTANCE: Symptomatic xanthogranulomas of the ventricular system
      are rare entities. No case of a massive hematoma in the xanthogranuloma, which
      may cause sudden deterioration, has been reported. This is the first report of a
      massive hematoma arising from a xanthogranuloma in the third ventricle. CLINICAL
      PRESENTATION: A 35-year-old woman was referred to our hospital with a 1-month
      history of progressively deteriorating consciousness. Neuroradiological findings
      revealed a mass in third ventricle and obstructive hydrocephalus. INTERVENTION:
      Bilateral external ventricular drainage was performed as an emergency treatment.
      Two weeks later, the mass was removed totally via the transcallosal
      transforaminal approach. The disturbance of consciousness completely disappeared
      2 weeks after the second operation. The pathological diagnosis was
      xanthogranuloma causing massive hematoma. CONCLUSION: The pathogenesis, clinical
      and radiological features, differential diagnosis, and treatment of this rare
      benign tumor are discussed. The hypothalamic dysfunction caused by a massive
      hematoma in the lesion of the third ventricle may cause sudden deterioration and
      death, whether the obstructive hydrocephalus exists. The risk of hemorrhage and
      hydrocephalus still remains after aspiration alone because of the presence of the
      cyst wall. Radical extirpation should be the choice of treatment for
      xanthogranulomas or colloid cysts of the third ventricle.

PMID- 8875493
TI  - Intramedullary neuroma of the cervical spinal cord: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intramedullary neuromas are rare tumors; only 37 cases
      have been described in the literature since 1931. CLINICAL PRESENTATION: The case
      of a 36-year-old woman presenting with an 8-month history of a progressive
      cervical myelopathy is reported. A diagnosis of a cervical intramedullary tumor
      was made by magnetic resonance imaging. INTERVENTION: A C3-C7 laminectomy and a
      near total resection were performed. Pathological examination revealed a neuroma;
      the various operative and pathological findings are presented. CONCLUSION: The
      existence of intraparenchymal neuromas is difficult to explain. Various
      pathogenic hypotheses are discussed. Microsurgical resection is considered the
      therapeutic option of choice for these entities.

PMID- 8875494
TI  - Hemianopic visual field defects in children with intracranial shunts: report of
      two cases.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial shunts are commonly placed in children and
      frequently require replacement during the child's growing years. Severe signs of
      increased intracranial pressure often are the first indication of shunt
      displacement and malfunction. Subtle neuro-ophthalmic signs in children are
      usually overlooked. CLINICAL PRESENTATION: Two cases are described in which
      homonymous hemianopsia resulted from unsuspected movement of the shunt catheter
      in growing children. In one male patient, the catheter tip impaled the optic
      tract, and in the other male patient the shunt became embedded in the midbrain
      tegmentum and shunt failure led to compression of the posterior cerebral artery.
      INTERVENTION: In the presence of optic atrophy, papilledema may go unnoticed
      without serial examinations. This stresses the importance of detecting other
      early warning signs of shunt displacement and increased intracranial pressure,
      including visual field changes and subtle abnormalities of motility. CONCLUSION:
      Because early diagnosis and shunt revision may allow visual recovery, children
      with shunts should be followed with visual fields and serial disc photographs.

PMID- 8875495
TI  - Optic nerve compression by a dolichoectatic internal carotid artery: case report.
AB  - OBJECTIVE AND IMPORTANCE: Compression of the optic nerve by a dolichoectatic
      internal carotid artery is a rare and correctable cause of visual loss. CLINICAL
      PRESENTATION: A young woman presented with right eye visual loss without obvious
      cause and was found to have compression of the right optic nerve by the
      ipsilateral internal carotid artery, as revealed by magnetic resonance imaging.
      INTERVENTION: Pterional craniotomy and decompression of the optic nerve by
      unroofing the optic canal resulted in improvement of vision in the affected eye.
      CONCLUSION: Compression of the optic nerve by a dolichoectatic internal carotid
      artery may produce visual loss. The disorder is well demonstrated by magnetic
      resonance imaging, and timely intervention can improve vision.

PMID- 8875496
TI  - Physiological diagnosis and surgical treatment of recurrent limb shaking: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Although recurrent limb shaking has been observed in
      patients with carotid occlusion, its cause, method of diagnosis, and definitive
      treatment have yet to be fully elucidated. This report examines the
      cerebrovascular physiology of a patient with recurrent limb shaking by means of
      xenon-enhanced computed tomographic (XeCT) scanning. By measuring cerebral blood
      flow (CBF) and cerebrovascular reserve capacity, we were able to confirm both the
      clinical diagnosis and the response to treatment on physiological grounds.
      CLINICAL PRESENTATION: The patient is a 49-year-old man who presented with
      frequent brief attacks of left arm and leg shaking that occurred at standing or
      coughing. After cervical radiation therapy for a laryngeal carcinoma, he was
      found to have bilateral carotid occlusion with minimal collateral development.
      XeCT scans revealed borderline ischemic perfusion and lack of cerebrovascular
      reserve in response to an acetazolamide vasodilatory challenge. INTERVENTION: The
      patient underwent a right superficial temporal artery to middle cerebral artery
      bypass to augment cerebral perfusion. CONCLUSION: After the procedure, the
      patient's limb shaking attacks ceased. The postoperative XeCT scan showed
      improved CBF and a return of cerebrovascular reserve capacity. Recurrent limb
      shaking is a manifestation of decreased CBF. Quantitative XeCT CBF studies
      coupled with vasodilatory challenge is an important way to assess patients with
      cerebrovascular disorders and thus identify individuals who will benefit from
      cerebral revascularization.

PMID- 8875497
TI  - The Axis Fixation System for posterior instrumentation of the cervical spine.

PMID- 8875498
TI  - Harvey Cushing (1869-1939).

PMID- 8875499
TI  - Hemispherical deafferentation: an alternative to functional hemispherectomy.

PMID- 8875500
TI  - Third ventricular cysticercal cyst mimicking a colloid cyst: case report.

PMID- 8875501
TI  - Hemangioblastomas of the spinal cord and the brainstem: diagnostic and
      therapeutic features.
AB  - Hemangioblastomas of the spinal cord and the brainstem make up 4% of all spinal
      tumors and are less common than cerebellar hemangioblastomas. CT and MRI are
      essential for preoperative diagnosis. Nevertheless, cerebral and spinal
      angiography are also mandatory, since they allow a detailed study of the vascular
      situation, which is decisive for exact planning of a surgical strategy. The
      purpose of this study was to evaluate the diagnostic and therapeutic factors
      which influence surgical morbidity and postoperative outcome. Twelve patients
      harbouring spinal(8 cases) or medullary (4 cases) hemangioblastomas, all
      symptomatic with sensorimotor deficits corresponding to the level of the lesion
      were evaluated. All patients were treated in our department between December 1989
      and September 1994. Complete resection of the lesion was achieved in each case.
      Postoperatively, none of the patients showed deterioration. Nine patients had
      immediate postoperative improvement of neurological signs and symptoms; in three
      patients the initial neurological deficits remained unchanged during the in
      patient period. Late postoperative outcome demonstrated a clear improvement; in
      only one patient was there no change of the clinical signs, while in the other 11
      patients a significant improvement of pre-existing neurological deficits was
      experienced. We conclude that microsurgical resection of spinal and medullary
      hemangioblastomas with low morbidity is feasible.

PMID- 8875502
TI  - Cranioplasty with bone flaps preserved under the scalp.
AB  - Cranial bone defects in 27 patients were repaired with bone flaps preserved under
      the scalp. Head trauma (thirteen patients), cerebrovascular disorder (five
      patients), postoperative brain swelling (seven patients), and cerebral infective
      disease (two patients) accounted for the cranial defects. The bone flaps are
      reimplanted after 14-98 days. The follow-up period was 6 to 26 months. We have
      encountered no complications related to this technique in 27 consecutive cases.

PMID- 8875504
TI  - Rhinological complications of sublabial transseptal transsphenoidal surgery for
      sellar and suprasellar lesions: prevention and management.
AB  - Transseptal transsphenoidal surgery is the most widely accepted operative
      procedure for sellar and suprasellar lesions. About 35% out of fifty-four cases
      operated by this procedure at our centre had rhinological complications. Possible
      mechanism involved and their prevention and management is discussed herewith.

PMID- 8875503
TI  - Lumbar spinal surgery for sciatica due to intervertebral disc disease in the
      elderly.
AB  - This report reviews 36 patients aged 71 to 93 years who had lumbar spinal surgery
      for sciatica pain some with motor and or sensory disturbances and with no motor
      and sensory disturbances. Even though we found soft disc herniations, these
      patients should have a thorough circumferential decompression because of bony
      osteophytes and facet hypertrophy. Special attention is drawn to the removal of
      herniated discs associated with massive spondylotic degenerative changes.

PMID- 8875505
TI  - The effect of immediate decompression on the optic nerve in retrobulbar hematoma.
AB  - We produced retrobulbar hematoma in both orbits of 10 pigs in order to assess the
      effects of blood elements and pressure created by the hematoma on the optic
      nerves. Ten other pigs were used as a control group. Following decompression in
      the right orbits, ocular movements, fundi, and intraocular pressure were
      evaluated for 6 weeks. At the end of the 6th week the optic nerves of 20 pigs
      were dissected bilaterally for measurements of ATP-ase activity and
      ultrastructural examination. The results of the ultrastructural examination of
      the optic nerves of the control group were normal. Optic nerves with decompressed
      retrobulbar hematoma showed minimal degeneration, whereas the nerves subjected to
      retrobulbar hematoma with no decompression showed significant degenerative
      changes. For all groups ATP-ase activities were measured and evaluated. Na+, K+
      ATP-ase activities decreased, while Ca+2, Mg+2 ATP-ase activities increased with
      the extent of degeneration. Optic nerve damage can develop after trauma.
      Decompression procedures are not among the causes of optic nerve degeneration but
      retrobulbar hematoma can result in optic neuropathy caused by the compression
      from the hematoma and the direct effect of blood waste products on the optic
      nerve.

PMID- 8875506
TI  - Spinal accessory nerve palsy due to neurovascular compression. Report of a case
      diagnosed by magnetic resonance imaging and magnetic resonance angiography.
AB  - The case of a young patient with left accessory nerve paralysis is reported. He
      had slight tilting of the head to the right side, developed over a period of
      about 6 months. On neurological examination hypotrophy of the left
      sternocleidomastoid and trapezius muscles was observed. MRI and MR-angiography
      imaged the presence of a neurovascular compression between the medulla oblungata,
      at the level of the nerve entry zone, and a vessel loop of an elongated left
      vertebral artery. In spite of the absence of a surgical demonstration it is our
      opinion that the neurovascular conflict is the cause of the accessory nerve
      palsy.

PMID- 8875507
TI  - Epidermoid cyst of the brain stem. Case report.
AB  - Brain stem epidermoid cysts are extremely rare lesions. Only nine cases have been
      reported. Management of the epidermoid cyst is decompression of cyst contents and
      removal of cyst capsule. But in some cases resection of the cyst may result in a
      poor outcome because of cyst wall adhesion into the brain stem.

PMID- 8875508
TI  - Local invasivity of glioblastoma multiforme with destruction of skull bone. Case
      report and review of the literature.
AB  - Primary tumors originating from cells of the glial lineage usually affect
      predominantly the white matter of the brain. Only rarely do gliomas destroy the
      surrounding bone by invasion of the extracellular matrix, especially without
      prior surgery. This paper describes the unusual case of a 66-year-old female
      patient with a left-sided intra- and extracranial tumor involving the temporal
      lobe, destroying the underlying skull base, and growing into the paranasal
      sinuses, orbit, and temporal bone. Biopsy revealed glioblastoma multiforme with
      strong GFAP positivity. Molecular biologic investigations of the p53, EGFR, and
      mdm2 genes showed functional inactivation of the p53 gene but no overexpression
      of oncogenes. Because the tumor was considered inoperable, palliative irradiation
      was carried out. The patient died 7 months after diagnosis. The causes of this
      phenomenon are discussed and the literature reviewed.

PMID- 8875509
TI  - Congenital cholesteatoma with spontaneous epidural abscess, sinus thrombosis and
      cutaneous fistula.
AB  - A congenital cholesteatoma or epidermoid is a benign mass that causes devastating
      effects if left untreated. An unusual case with a congenital cholesteatoma
      located in the mastoid region complicated by epidural abscess, sinus thrombosis,
      and cutaneous fistula is presented. The patient had normal otologic findings and
      had no neurologic deficit. A review of the literature found no report of a
      similar case.

PMID- 8875510
TI  - Cerebral salt wasting syndrome.
AB  - Hyponatremia following acute or chronic central nervous system injury which is
      due to excessive Na+ loss in the urine without an increase in the body fluid, has
      been described as Cerebral Salt Wasting Syndrome (CSWS). This syndrome is often
      confused with dilutional hyponatremia secondary to inappropriate ADH secretion.
      Accurate diagnosis and management are mandatory for to improve the course of the
      disease. In this study a patient with CSW Syndrome is presented and the treatment
      and diagnosis of this syndrome are discussed in view of the literature.

PMID- 8875511
TI  - Primary intraosseous meningioma of the temporal bone in an infant. A case report.
AB  - Primary intraosseous meningioma of the skull bone is a very rare entity. Although
      it can occur at any age, it is very rare in children. We present a case and
      review the literature.

PMID- 8875512
TI  - Spinal metastases of cerebral glioma. Case report.
AB  - We report a case of multiple spinal leptomeningeal metastases from an
      intracerebral glioblastoma and the original tumor having been an oligoastrocytoma
      (WHO II). Three time resection of this right frontal tumor with opening of the
      lateral ventricle preceded intraventricular spread. Diagnosis of spinal
      dissemination was based on the previous history and Gadolineum-DTPA enhanced MR.

PMID- 8875513
TI  - Bacterial products and the control of ingestive behavior: clinical implications.
AB  - Bacterial products such as lipopolysaccharides (LPS) and muramyl peptides are
      delivered in the course of infections. They trigger the host's acute phase
      responses to bacterial infections and are probably involved in the accompanying
      hypophagia because LPS and muramyl dipeptide (MDP, the minimal immunologically
      active muramyl peptide) reduce food intake after parenteral administration in
      animals. LPS and MDP inhibit feeding synergistically through separate but
      interacting mechanisms. The hypophagic effects of LPS and MDP are presumably
      mediated by the combined actions of interleukin-1, tumor necrosis factor, and
      other cytokines. More work is required to understand the interactions between
      these cytokines, and between bacterial products and cytokines, before cytokine
      antagonists can be used for treatment of the hypophagia during bacterial
      infections. As the hypophagia seems to be an early mechanism of host defense, a
      treatment should be carefully considered. If an intervention is indicated because
      of a patient's poor condition, inhibitors of eicosanoid synthesis and
      glucocorticoids may hold more promise for therapy because such substances block
      LPS and MDP hypophagia. Although LPS can reduce food intake by direct action on
      the brain, presently available evidence indicates that systemic LPS acts
      primarily in the periphery to generate a neural signal that is transmitted to the
      brain and inhibits feeding through the vagus. The exact site where LPS acts on
      peripheral nerves remains to be identified. LPS hypophagia is conditionable, but
      conditioning cannot solely account for LPS hypophagia under most test conditions.
      Whether MDP hypophagia is also conditionable and mediated by vagal afferents is
      not yet known. All in all, the putative mediators and mechanisms of LPS and MDP
      hypophagia suggest some options for a treatment of the hypophagia during
      bacterial infection, but present knowledge about the mechanisms and interactions
      of the involved substances is still fragmentary and requires further
      investigation.

PMID- 8875514
TI  - Effect of parenteral L-glutamine on muscle in the very severely ill.
AB  - Glutamine (Gln)-supplemented perioperative total parenteral nutrition (TPN) has
      been reported to reduce the loss of intramuscular glutamine following routine
      surgery. This study investigates whether glutamine-supplemented TPN can alter
      muscle biochemistry acutely in the very severely ill patient. Thirty-eight
      patients (age 19-77 yr; mean 55 yr), critically ill (APACHE II range 8-31; median
      17) admitted to the intensive care unit (ICU) were recruited to receive either
      conventional TPN (CTPN) or an isonitrogenous, isoenergetic feed supplemented with
      25 g crystalline L-glutamine per 24 h (GTPN) in a prospective, double blind,
      block-randomized study. In a representative sample of these patients, relatives
      consented to a paired muscle biopsy taken before feeding (10 GTPN/9 CTPN
      patients; ICU Day 2-4) and repeated 5 days later (16 patients; ICU Day 7-9).
      Muscle biopsies and matching plasma samples were analyzed using a coupled
      glutaminase-glutamate dehydrogenase enzymatic assay. A correction was made using
      sodium to account for the massive changes in extracellular fluid volume. The
      average muscle Gln content before feeding was very low. Between biopsies no
      consistent pattern of change was seen with or without exogenous Gln. It also
      proved difficult in these very sick patients to correct a low plasma Gln with L
      Gln-TPN during the initial phase of the severe illness. TPN supplementation with
      25 g/24 h, L-glutamine appears inadequate in the acute period to counteract the
      muscle and plasma biochemical changes seen in these patients. It is unknown
      whether any larger dose could alter this state.

PMID- 8875515
TI  - Nutrition and learning in Chilean school age children: Chile's Metropolitan
      Region Survey 1986-1987.
AB  - The objective of this study was to determine the interrelationship between the
      scholastic achievement (SA) test and nutritional status of a representative
      sample of 4,509 elementary and high school children from Chile's Metropolitan
      Region. Percentages of weight/age (W/A), height/age (H/A), and weight/height
      (W/H) were compared to WHO (World Health Organization) Tables, head
      circumference/age (HC/A) to the Tanner Tables, and brachial anthropometry to
      Frisancho's norms. Socioeconomic status (SES) was measured by means of Graffar's
      Modified Method; SA by means of a language and mathematics test. Statistical
      analysis included correlation, regression, and WHO risk-approach methodology.
      Results showed that HC/A was the anthropometric parameter with the greatest
      explanatory power in SA variance and was significantly greater in high school
      graduates who were 17 y old (r = 0.350; p < 0.001; r2 = 0.122) than in elementary
      school children, who were 6 y old (r = 0.227; p < 0.001; r2 = 0.049), with a
      relative risk of 2.1 and 1.5, respectively. The explanatory power of W/A and H/A
      in SA variance was significantly decreased, and no significant differences were
      observed among high school students. These findings confirm that HC/A is the most
      important anthropometric parameter associated with SA. Educational selectivity
      apparently relates to HC/A, and not to W/A or H/A. These results may be useful in
      planning nutritional and educational policies.

PMID- 8875516
TI  - Hypermetabolism and increased peripheral release of amino acids after
      subarachnoidal hemorrhage and its operative treatment.
AB  - The metabolic response to surgery for acute subarachnoidal hemorrhage and its
      modification by amino acid infusions was studied. Thirty patients with acute
      subarachnoidal hemorrhage were randomly assigned to receive for 12 h either an
      infusion of glucose and a balanced amino acid solution (1.68 MJ = 400 kcal/d and
      0.15 gN.kg-1.d-1; group AA) or a glucose and a solution containing 20% of total
      nitrogen as alanyl-glutamine (1.68 MJ = 400 kcal/d and 0.15 gN.kg-1.d-1; group
      ALAGLN). A separate control group received glucose alone (1.68 MJ = 400 kcal/d).
      The infusions started 12 h after operation. All patients received
      corticosteroids. Despite a higher arterial glutamine concentration in the ALAGLN
      group (791 +/- 195 mumol/L vs. AA 581 +/- 112 mumol/L, and control 571 +/- 82
      mumol/L; p < 0.05) the net release of glutamine from the leg was similar in all
      groups (ALAGLN: 39 +/- 47 mumol/min, AA: 26 +/- 18 mumol/min, and control: 24 +/-
      14 mumol/min, NS). Also the release of alanine (ALAGLN: 35 +/- 24 mumol/min, AA:
      34 +/- 24 mumol/min, and control: 30 +/- 18 mumol/min) and total amino acids
      (ALAGLN: 133 +/- 131 mumol/min, AA: 125 +/- 98 mumol/min, and control: 112 +/- 72
      mumol/min) were similar in all groups. All groups were characterized by a pattern
      of preoperative hypermetabolism that persisted after the operation. The
      hypermetabolism was not related to increased peripheral oxygen consumption, since
      femoral oxygen consumption (VO2) represented only 3% of the whole body VO2-.

PMID- 8875517
TI  - The use of an intravenous fish oil emulsion enriched with omega-3 fatty acids in
      patients with cystic fibrosis.
AB  - The effects of parenteral nutrition supplemented with a lipid emulsion enriched
      with the omega-3 fatty acids (FA), eicosapentaenoate (20:5n-3) and
      docosahexaenoate (22:6n-3), derived from fish oil were compared to a standard
      lipid emulsion containing omega-6 FA in patients with cystic fibrosis (CF).
      Patients were randomized to receive either Omegavenous 10%, which contains fish
      oil (IFO), or Liposyn III 10% (control) daily for 1 mo at a dose of 150 mg/kg.
      There were no observed allergic or toxic reactions, no abnormalities in liver
      function tests or coagulation parameters. To assess the bioavailability of the
      lipid administered, measurement of plasma free fatty acid (FFA) levels were made
      of the essential FA. There were no adverse changes in plasma levels of the omega
      6 FA (18:2n-6, 18:3n-6, 20:3n-6, and 20:4n-6), and plasma levels of the omega-3
      FA (20:5n-3 and 22:6n-3) increased significantly during the 1-mo study. There
      were no significant changes in plasma FFA profiles of the essential FA for the
      patients receiving the control lipid. The effect of treatment on pulmonary
      function was also investigated. There were no significant changes in FVC, FEV1,
      PEFR, FEV1/ FVC, or FEF25-75 (absolute value or percentage) over the 4 weeks of
      study in the group receiving IFO or control. This preliminary investigation
      suggests that intravenous administration of fish oils enriched with long chain
      omega-3 FA to patients with CF is safe and bioavailable.

PMID- 8875518
TI  - Necrotizing enterocolitis and total parenteral nutrition-associated cholestasis.
AB  - The proportion of patients with total parenteral nutrition (TPN)-associated
      cholestasis (TPN-AC) who have necrotizing enterocolitis (NEC) has increased
      markedly in the past ten years. Little is known about how these diseases affect
      each other. We retrospectively studied 24 patients with NEC and bowel necrosis or
      perforation who required surgical intervention. Patients were divided into two
      groups: those who had received TPN (NEC + TPN, n = 17) and those who had not
      (NEC, n = 7). As cholestasis was present clinically, or prolonged TPN was
      anticipated, liver biopsy was done. Bile acid levels were measured in both serum
      and bile in 13 patients. Six patients, who underwent bowel resection and
      enterostomy, had a second liver biopsy and measurement of bile acid levels at
      stoma closure. Our results showed that in 13 patients for whom bile acid levels
      were measured (NEC + TPN, n = 6) (NEC, n = 7), serum bile acid level was
      significantly elevated in both groups over normal for age. Biliary bile acid
      levels were correspondingly depressed in both groups suggesting a failure of bile
      acid transport. All patients had abnormal liver histology, but the pattern of
      injury differed between the two groups. Those in the NEC group had biliary stasis
      and mild hepatocyte degeneration. In contrast, 15 of 17 in the NEC + TPN group
      had advanced injury specific for TPN-AC. All six patients managed on TPN and
      partial enteral feeding before a second biopsy had no change in bile acid levels
      and progression of histologic injury. We conclude that NEC alone can cause
      functional cholestasis and histologic liver injury but does not cause the
      specific progressive damage caused by TPN. NEC may make the liver more
      susceptible to the effects of TPN. Partial enteral feeding does not halt or
      reverse this injury.

PMID- 8875519
TI  - Zinc status and serum testosterone levels of healthy adults.
AB  - Zinc deficiency is prevalent throughout the world, including the USA. Severe and
      moderate deficiency of zinc is associated with hypogonadism in men. However, the
      effect of marginal zinc deficiency on serum testosterone concentration is not
      known. We studied the relationship between cellular zinc concentrations and serum
      testosterone cross-sectionally in 40 normal men, 20 to 80 y of age. In four
      normal young men (27.5 +/- 0.5 y), we measured serum testosterone before and
      during marginal zinc deficiency induced by restricting dietary zinc intake. We
      also measured serum testosterone in nine elderly men (64 +/- 9 y) who were
      marginally zinc deficient before and after 3 to 6 mo of supplementation with 459
      mumol/ d oral zinc administered as zinc gluconate. Serum testosterone
      concentrations were significantly correlated with cellular zinc concentrations in
      the cross-sectional study (lymphocyte zinc versus serum testosterone, r = 0.43, p
      = 0.006; granulocyte zinc versus serum testosterone, r = 0.30, p = 0.03). Dietary
      zinc restriction in normal young men was associated with a significant decrease
      in serum testosterone concentrations after 20 weeks of zinc restriction (baseline
      versus post-zinc restriction mean +/- SD, 39.9 +/- 7.1 versus 10.6 +/- 3.6
      nmol/L, respectively; p = 0.005). Zinc supplementation of marginally zinc
      deficient normal elderly men for six months resulted in an increase in serum
      testosterone from 8.3 +/- 6.3 to 16.0 +/- 4.4 nmol/L (p = 0.02). We conclude that
      zinc may play an important role in modulating serum testosterone levels in normal
      men.

PMID- 8875521
TI  - Acute niacin deficiency.

PMID- 8875520
TI  - Effect of L-glutamine supplementation on impaired glucose regulation during
      intravenous lipid administration.
AB  - In contrast to L-glutamine, lipid emulsions are routinely administered to
      patients receiving nutritional support. The provision of fat during intravenous
      feeding is essential, but the potentially toxic byproducts of fatty acid
      oxidation may have adverse metabolic consequences. In the present study, we have
      examined the effect of L-glutamine, an inhibitor of fatty acid oxidation, on the
      development of defective blood glucose regulation caused by a 48-hour infusion of
      10% intralipid in rats. Male Sprague-Dawley rats (200-290 g) were anesthetized
      with sodium pentobarbital, the right femoral vein cannulated, and baseline blood
      samples were taken. Each rat was placed in a metabolic cage with access to water,
      in the presence or absence of rodent chow. Two hours after waking, the rats were
      infused with 10% intralipid with either saline (control), 2% L-glutamine, or 2% L
      alanine. After 48 hours, all animals were sacrificed and blood samples were again
      obtained. The mean +/- SEM plasma glucose levels before and after lipid infusion
      at the rate of 1 mL/hr in control rats fed ad libitum, were 125 +/- 13 and 170 +/
      5 mg/dL (p < 0.01, n = 7). Similarly, plasma free fatty acids (FFA) in these
      animals rose from 0.74 +/- 0.11 to 1.34 +/- 0.32 mmol/L (p < 0.05). Plasma
      insulin levels also increased from 337 +/- 44 to 1278 +/- 88 pg/mL (p < 0.01).
      Reduction of intralipid dose infusion did not prevent insulin resistance
      characterized by hyperglycemia and hyperinsulinemia. However, addition of L
      glutamine to the high-dose lipid infusion with chow feeding prevented changes in
      plasma glucose, insulin levels, and FFA but not triglyceride levels. Also,
      glutamine but not alanine supplementation in intralipid infused rats without chow
      feeding prevented changes in plasma glucose, insulin, and malondialdehyde levels.
      In conclusion, these data show that glutamine supplementation during intravenous
      lipid administration in rats prevents the development of impaired glucose
      regulation associated with hyperlipidemia.

PMID- 8875522
TI  - Nutritional issues in cancer management.
AB  - The objective of this article was to investigate the relationship between
      nutrition and cancer, as it relates to the initiation, promotion, and treatment
      of tumor growth. English-language studies published in the last 25 years were
      retrieved using MEDLINE, bibliographies, and consultation with experts. MEDLINE
      search terms included "cancer", "malnutrition," and "nutritional support." In
      vitro and in vivo controlled studies addressing the impact of nutritional factors
      on cancer prevention and treatment were selected. Approximately 30% of cancers in
      the Western countries are diet-related. The presence of malignancy affects
      patients' nutritional status negatively, leading to increased morbidity and
      mortality. Standard nutritional support (both enteral and parenteral) is not
      always effective in significantly improving outcome in malnourished cancer
      patients, due to characteristic changes in host metabolism. Preliminary studies
      suggest that newer nutritional-pharmacologic agents may be beneficial in
      counteracting the derangement of host metabolism, and consequently in
      ameliorating cancer patients' nutritional status and outcome of malnourishment.
      This review suggests that dietary manipulations and nutritional-pharmacologic
      therapy might be highly effective adjuncts in controlling the symptoms of
      patients with neoplastic disease.

PMID- 8875523
TI  - Fish oil as a therapy for lung disease.

PMID- 8875524
TI  - Another potential clinical role for glutamine-supplemented parenteral nutrition?

PMID- 8875525
TI  - Nutrition and coronary heart disease in the elderly: low fat or laissez-faire?

PMID- 8875526
TI  - Antioxidants, dietary fat saturation, lipoprotein oxidation and atherogenesis.

PMID- 8875527
TI  - Making the public and pediatric community aware of the importance of fatty acids
      in infant nutrition.

PMID- 8875529
TI  - Clinical practice improvement: a new methodology for outcomes research.

PMID- 8875528
TI  - Nutrition labeling to prevent deficiency, promote health, and avert toxicity.

PMID- 8875530
TI  - Nutritional epidemiology: methods and innovations used in a central European
      community-based program.

PMID- 8875531
TI  - Organic phosphates in parenteral nutrition: pouring fresh water into an old
      bucket.

PMID- 8875532
TI  - Afferent discharges from osmoreceptors in the liver of the guinea pig. 1969.

PMID- 8875533
TI  - Update: NIH consensus conference. Gastrointestinal surgery for severe obesity.
AB  - The 1991 Consensus Development Panel was instrumental both in establishing
      criteria for selection of patients for surgical treatment and in recognition of
      operations that have been shown to be safe and reasonably effective in the long
      term. The Panel may have been premature in endorsement of any form of banded
      gastroplasty because the long-term weight loss results of these procedures are
      frequently disappointing. It seems likely that a consensus panel on the same
      subject would be worthwhile in the next decade to carefully evaluate such
      procedures as biliopancreatic bypass and the various laparoscopic techniques for
      gastric banding. In 1996 surgery remains the only effective treatment for
      patients with medically severe (morbid) obesity.

PMID- 8875534
TI  - Studies on nutritional status in general surgery patients by clinical,
      anthropometric, and laboratory parameters.
AB  - We assessed the nutritional status of general surgery patients with and without
      cancer from a western European population in this prospective study. Anamnestic
      (weight development, abdominal complaints) and anthropometric (fat tissue
      measurements) data were collected on six groups of patients: cancer of the
      stomach (n = 13), pancreas (n = 13), colorectal (n = 23), breast (n = 12), and
      two control groups with benign diseases, ages 20-45 and 50-75 y. From these data,
      body mass index and ideal body weight were calculated. Concentrations of albumin,
      transferrin, retinol-binding protein, prealbumin, and creatinine height index
      were determined by biochemical tests. A weight loss of more than 10% was found in
      only 31% of gastric and 61% of pancreatic cancer patients. Significant values
      from anthropometric data were also found only in these groups. In biochemical
      tests, only the creatinine height index was reduced in all patients with
      pancreatic cancer. The remaining laboratory changes were so unspecific in all
      other parameters that no conclusions could be drawn as to the status of the
      patient's nutritional condition. For the evaluation of nutritional status, only
      relatively simple and inexpensive anamnestic and anthropometric measurements are
      necessary.

PMID- 8875536
TI  - Body mass index at different ages and its association with height at age 14 and
      with the whole growing process.
AB  - The relevance of the association of the body mass index (BMI) at 1,4,6, and 12
      years of age with the growing process and its capacity for predicting height at
      age 14 was investigated in a sample of 354 adolescents (182 boys and 172 girls).
      Regression analysis showed that body bulk at various ages, as expressed by the
      BMI is closely related with the height attained at age 14, and longitudinal
      principal components analysis suggested that it is also associated with the whole
      growing process. The way in which BMI affects height could be related with the
      stage of sexual development, which seems to play an intermediate role in the
      pathway linking body bulk and height.

PMID- 8875535
TI  - Effect of iron-supplemented total parenteral nutrition in patients with iron
      deficiency anemia.
AB  - Iron deficiency anemia is common among hospitalized patients, and blood losses
      from diagnostic phlebotomy increase the likelihood of a negative iron balance.
      The role for iron supplementation of total parenteral nutrition (TPN) in these
      patients is unclear. Twenty-three patients with iron deficiency anemia were
      identified. Twelve patients were randomized to receive TPN without iron (group 1)
      and 11 received TPN supplemented with 10 mg of iron as iron dextran daily (group
      2). Both groups were matched for age, serum iron studies, red cell indices, and
      hemogram. After a 7-d period, the mean serum iron in group 2 increased from 10 to
      26 micrograms/dL, with an increased transferrin saturation from 7.3 to 15.3%
      (each, p < 0.05). No changes in total iron binding capacity, ferritin,
      reticulocyte count, hemoglobin, hematocrit, or mean corpuscular volume were
      observed in the two groups. The incidence of infectious complications was not
      different between both groups. We conclude that iron supplementation of TPN
      appears safe and is effective in increasing serum iron levels. The use of iron
      supplemented short-term TPN needs to be further studied given no change in red
      cell indices, hemoglobin, hematocrit, or transfusion requirement.

PMID- 8875537
TI  - Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids,
      and nucleotide-enriched enteral feeding: a randomized prospective comparison with
      standard enteral and low calorie/low fat i.v. solutions.
AB  - In a prospective randomized trial in patients undergoing major abdominal surgery,
      the impact of a new enteral formula supplemented with arginine, omega-3 fatty
      acids, and nucleotides (A, n = 14) on immunological parameters was compared with
      a standard enteral formula (B, n = 14) and a low calorie/low fat intravenous
      solution (C, n = 13). Four days postoperatively, a statistically significant
      decrease in total leukocyte count (A, 9.0 +/- 2.9; B, 8.0 +/- 2.4; C, 11.1 +/-
      3.5 x 10(6) cells/mL; A versus C, B versus C; p < 0.05), higher percentage of
      lymphocytes (A, 14.3 +/- 4.9; C, 8.2 +/- 6.1; p < 0.05), and decreased median CRP
      levels (A, 80.4 [69.9]; B, 70 [74]; C, 88.5 [142] in mg/L; A versus C, p < 0.05;
      B versus C; p < 0.05) were observed in the enteral nutrition groups. The
      expression of activated surface antigen HLA-DR was diminished on CD14+ cells over
      4 d (A, 58.2 [39.2]; B, 52.2 [36.2]; C, 76.6 [25.2] in %; A versus C, p < 0.05; B
      versus C, p < 0.05) and 8-10 d (A, 37.9 [31.4]; C, 58.5 [37.6]; p < 0.05)
      postoperatively. Significantly enhanced median phagocytic activity of CD14+
      monocytes and granulocytes was observed in group C 8-10 days postoperatively (A,
      83.3 [11.8]; B, 71.6 [34.1]; C, 87.4 [10.8]; A versus B, B versus C, p < 0.05;
      and A, 75.7 [10.0]; B, 69.0 [37.8]; C, 80.0 [10.1] in %, B versus C, p < 0.05,
      respectively). Postoperative hospital and intensive care unit stay was similar
      among the three groups; however, infectious complications were less frequent in
      group A (A versus C, p = 0.15). Thus, a modified enteral nutritional support and
      supplementation may influence the immune competence toward a more efficient
      defense response.

PMID- 8875538
TI  - Weighed dietary intakes in patients with chronic liver disease.
AB  - Poor dietary intake is assumed to be a major causal factor in the malnutrition
      observed in patients with chronic liver disease. However, the dietary habits of
      this patient population are poorly documented. The aim of this study was to
      assess weighed dietary intakes in hospitalized patients with chronic liver
      disease. Twenty patients with liver disease (10 men, 10 women; mean +/- SD age,
      46.2 +/- 10.9 yr, mean weight, 63.3 +/- 8.0 kg, mean body mass index, 22.1 +/-
      2.8 kg/m2; 10 alcoholic, 10 nonalcoholic) and 20 general medical patients,
      matched for age and sex, underwent a 3-d weighed assessment of dietary intake. No
      significant differences were observed in food intake or dietary composition
      between the patients with liver disease and the hospital controls. Patients with
      alcoholic liver disease showed significant differences in dietary energy,
      protein, and carbohydrate intakes compared with the patients with nonalcoholic
      liver disease when data were expressed in absolute terms but not when expressed
      relative to body weight; dietary composition was similar in both groups. Overall,
      patients with chronic liver disease, especially those with alcohol-related
      injury, consume a diet comparable with that ingested by other hospital patients
      both in amount and composition.

PMID- 8875539
TI  - Effect of a parenteral nucleoside-nucleotide mixture on hepatic metabolism in
      partially hepatectomized cirrhotic rats.
AB  - After hepatectomy, purine and pyrimidine metabolism is a key process in synthesis
      of DNA and RNA and in energy metabolism. To supply nucleosides for salvage
      synthesis, nucleoside-nucleotide mixture solutions have been developed, and they
      have been found to improve protein metabolism and hepatic regeneration after
      partial hepatectomy in normal rats. However, the effect of the solution in
      cirrhotic liver, common in patients with hepatocellular carcinoma, has not been
      reported. The aim of this study was to evaluate the metabolic effect of the
      nucleoside-nucleotide mixture on cirrhotic rats after partial hepatectomy.
      Seventy percent partial hepatectomy was performed in thioacetamide-administered
      cirrhotic rats. The fractional protein synthetic rate, nitrogen balance, hepatic
      content of nucleic acid, and blood chemistry after the administration of the
      nucleoside-nucleotide mixture solution (OG-VI) with total parenteral nutrition
      was evaluated at 7 d after partial hepatectomy. OG-VI increased hepatic RNA level
      and hepatic fractional protein synthetic rate (p < 0.05). It is concluded that
      the nucleoside-nucleotide mixture solution is an effective nutritional supplement
      to the metabolism of cirrhotic rats after partial hepatectomy.

PMID- 8875540
TI  - Gastroduodenal decompression and simultaneous nasoenteral nutrition:
      "extracorporeal gastrojejunostomy".
AB  - The term "extracorporeal gastrojejunostomy" is being proposed to connote the
      process of refeeding gastric aspirates along with enteral nutritional support
      administered distally into the duodenum or jejunum. Although the procedure itself
      is common and known to clinicians, it is believed that the introduction and
      popularization of this unusual expression will heighten awareness of this
      approach. This can be achieved by using one multilumen tube or two tubes, one for
      gastric aspiration and one for distal feeding.

PMID- 8875542
TI  - Vitamin D3 and chemotherapy-induced alopecia.

PMID- 8875541
TI  - Influence of nutrition on liver oxidative metabolism.
AB  - The liver plays a major role in the disposition of the majority of drugs. This is
      due to the presence of several drug-metabolizing enzyme systems, including a
      group of membrane-bound mixed-function oxidative enzymes, mainly the cytochrome
      P450 system. Hepatic oxidative capacity can be assessed by changes in antipyrine
      metabolism. Different drugs and other factors may induce or inhibit the
      cytochrome P450-dependent system. This effect is important in terms of the
      efficacy or toxicity of drugs that are substrates for the system. Microsomal
      oxidation in animals fed with protein-deficient diets is depressed. The mixed
      function oxidase activity recovers after a hyperproteic diet or the addition of
      lipids. Similar findings have been reported in patients with protein-calorie
      malnutrition, although results in the elderly are conflicting. Different studies
      have revealed that microsomal oxidation is impaired by total parenteral nutrition
      and that this effect is absent when changing the caloric source from
      carbohydrates to a conventional amino acid solution or after lipid addition,
      especially when administered as medium-chain/long-chain triglyceride mixtures.
      Peripheral parenteral nutrition appears to increase antipyrine clearance.

PMID- 8875543
TI  - Cooked food mutagens and breast cancer.

PMID- 8875545
TI  - The right weight: body fat, menarche, and fertility.

PMID- 8875544
TI  - Update on monosodium glutamate: sensory properties and safety.

PMID- 8875546
TI  - To be or not to be (for-profit).

PMID- 8875548
TI  - Survival analysis.

PMID- 8875547
TI  - Muscle mass, survival, and the elderly ICU patient.

PMID- 8875549
TI  - Clinical delivery of nutritional therapy: automated compounders and patient
      specific feeding.

PMID- 8875550
TI  - The role of industry-based dietitians in translating science to practice: a
      personal view.

PMID- 8875551
TI  - Phytoestrogen content of foods--a compendium of literature values.
AB  - Plant compounds with estrogenic activity may play a role in cancer prevention,
      moderation of menopausal symptoms, and other health effects. To facilitate
      research on these possible actions, the literature was reviewed for quantitative
      data on the levels of known phytoestrogens (daidzein, genistein, coumestrol,
      formononetin, and biochanin A) in food plants. For comparative purposes, all
      phytoestrogen levels were recalculated on a wet weight basis. Details on analytic
      procedures are given as well. High-performance liquid chromatography was the
      method most often used to analyze these compounds in foods. Most significant
      sources of isoflavone and coumestan phytoestrogens include soybeans, soy flour,
      soy flakes, isolated soy protein, traditional soy foods such as tofu and soy
      drinks, second-generation say foods, sprouts, and other legumes. Finally, medians
      among reported values of phytoestrogen content are provided for some of the most
      commonly eaten foods with quantitative data available. These may be used to
      calculate dietary intake of daidzein, genistein, coumestrol, formononetin, and
      biochanin A.

PMID- 8875552
TI  - Dietary conjugated linoleic acid modulation of phorbol ester skin tumor
      promotion.
AB  - The fatty acid derivative conjugated dienoic linoleate (CLA) has been shown to
      inhibit initiation and postinitiation stages of carcinogenesis in several
      experimental animal models. The goal of the present study was to determine the
      role of increasing levels of dietary CLA in mouse skin tumor promotion elicited
      by 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed control (no CLA)
      diet during initiation, then switched to diets containing 0.0%, 0.5%, 1.0%, or
      1.5% (wt/wt) CLA during skin tumor promotion by TPA. Body weights of mice fed
      0.5%, 1.0%, or 1.5% CLA were similar to each other but were significantly lower
      (p < 0.05) than weights of mice fed no CLA (0.0%) throughout promotion. A
      reduction in papilloma incidence was observed in mice fed 1.5% CLA from Weeks 8
      to 24 compared with mice fed diets containing 0.0-1.0% CLA (p < 0.05). Twenty
      four weeks after tumor promotion was begun, diets containing 1.0% and 1.5% CLA
      inhibited tumor yield (4.94 and 4.35 tumors/mouse, respectively) compared with
      diets without CLA (0.0% CLA, 6.65 tumors/mouse, p < 0.05) or 0.5% CLA (5.92
      tumors/mouse, p < 0.05). These data indicate that CLA inhibits tumor promotion in
      a manner that is independent of its anti-initiator activity. Further studies are
      warranted in identifying cellular mechanisms that are likely to be involved with
      the antipromoter effects of CLA.

PMID- 8875553
TI  - Antitumorigenic effect of a mammalian lignan precursor from flaxseed.
AB  - Secoisolariciresinol diglycoside (SD), a mammalian lignan precursor found in high
      fiber foods, was isolated from flaxseed and tested for effects on mammary
      tumorigenesis in rats fed a high-fat (20%) diet. Ingestion of purified SD at 1.5
      mg/day for 20 weeks starting 1 week after treatment with the carcinogen
      dimethylbenzanthracene resulted in a 37% reduction (p < 0.05) in the number of
      tumors per tumor-bearing rat and a 46% reduction (p < 0.05) in the number of
      tumors per tumor-bearing rat and a 46% reduction (p < 0.05) in the number of
      tumors per number of rats in each group. Urinary mammalian lignan excretion
      significantly increased (p < 0.0001) with SD treatment, indicating the conversion
      of SD to mammalian lignans. No enlargement or gross abnormalities of the major
      organs were observed in the SD-treated rats. This study showed, for the first
      time, that SD has an antitumor effect when provided at the early promotion stage
      of tumorigenesis and may contribute to the health benefits of high-fiber foods.

PMID- 8875554
TI  - Inhibition of human breast cancer cell proliferation and delay of mammary
      tumorigenesis by flavonoids and citrus juices.
AB  - Two citrus flavonoids, hesperetin and naringenin, found in oranges and
      grapefruit, respectively, and four noncitrus flavonoids, baicalein, galangin,
      genistein, and quercetin, were tested singly and in one-to-one combinations for
      their effects on proliferation and growth of a human breast carcinoma cell line,
      MDA-MB-435. The concentration at which cell proliferation was inhibited by 50%
      (IC50), based on incorporation of [3H]thymidine, varied from 5.9 to 140
      micrograms/ml for the single flavonoids, with the most potent being baicalein.
      IC50 values for the one-to-one combinations ranged from 4.7 micrograms/ml
      (quercetin + hesperetin, quercetin + naringenin) to 22.5 micrograms/ml
      (naringenin + hesperetin). All the flavonoids showed low cytotoxicity (> 500
      micrograms/ml for 50% cell death). Naringenin is present in grapefruit mainly as
      its glycosylated form, naringin. These compounds, as well as grapefruit and
      orange juice concentrates, were tested for their ability to inhibit development
      of mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female
      Sprague-Dawley rats. Two experiments were conducted in which groups of 21 rats
      were fed a semipurified diet containing 5% corn oil and were given a 5-mg dose of
      DMBA intragastrically at approximately 50 days of age while in diestrus. One week
      later, individual groups were given double-strength grapefruit juice or orange
      juice or fed naringin or naringenin at levels comparable to that provided by the
      grapefruit juice; in the second experiment, the rats were fed a semipurified diet
      containing 20% corn oil at that time. As expected, rats fed the high-fat diet
      developed more tumors than rats fed the low-fat diet, but in both experiments
      tumor development was delayed in the groups given orange juice or fed the
      naringin-supplemented diet compared with the other three groups. Although tumor
      incidence and tumor burden (grams of tumor/rat) were somewhat variable in the
      different groups, rats given orange juice had a smaller tumor burden than
      controls, although they grew better than any of the other groups. These
      experiments provide evidence of anticancer properties of orange juice and
      indicate that citrus flavonoids are effective inhibitors of human breast cancer
      cell proliferation in vitro, especially when paired with quercetin, which is
      widely distributed in other foods.

PMID- 8875555
TI  - Importance of the form of topical vitamin E for prevention of
      photocarcinogenesis.
AB  - With increasing solar ultraviolet (UV)-B radiation reaching the Earth's surface
      and the incidence of skin cancer rising steadily, there is an ever-increasing
      need to determine agents that modulate photocarcinogenesis and to understand the
      mechanisms underlying this modulation. Our laboratory has demonstrated that
      topical application of the dl-alpha-tocopherol form of vitamin E to mice prevents
      skin cancer and the immunosuppression induced by UVB irradiation. However, dl
      alpha-tocopherol has limited stability at room temperature. The current study was
      designed to ask whether the thermostable esters of vitamin E, alpha-tocopheryl
      acetate, or alpha-tocopheryl succinate prevent skin cancer and immunosuppression
      induced in mice by UV radiation. In the alpha-tocopheryl acetate study, skin
      cancers developed in 70% of UVB-irradiated control mice and in 90%, 73%, and 90%
      of mice receiving topical applications of 12.5, 25, and 50 mg of dl-alpha
      tocopheryl acetate, respectively. In the alpha-tocopheryl succinate study, skin
      cancer developed in 59.3% of control UVB-irradiated mice and in 82%, 100%, and
      81.5% of mice treated with 2.5, 12.5, and 25 mg d-alpha-tocopheryl succinate,
      respectively. Thus neither alpha-tocopheryl acetate nor alpha-tocopheryl
      succinate prevented photocarcinogenesis. At 12.5 and 25 mg/treatment, alpha
      tocopheryl acetate and alpha-tocopheryl succinate, respectively, enhanced
      photocarcinogenesis (p = 0.0114 and 0.0262, respectively, log rank test). On the
      basis of high-performance liquid chromatography analysis at 16-17 weeks after the
      first vitamin E treatment, the esterified forms of vitamin E applied
      epicutaneously accumulated in the skin, but the levels of free alpha-tocopherol
      remained low. Neither alpha-tocopheryl acetate nor alpha-tocopheryl succinate
      prevented the induction by UV radiation of immunosusceptibility to implanted
      syngeneic antigenic UV-induced tumor cells. Thus alpha-tocopheryl acetate or
      alpha-tocopheryl succinate not only failed to prevent photocarcinogenesis, but
      may have enhanced to process. Considering that alpha-tocopherol esters are
      included in many skin lotions, cosmetics, and sunscreens, further studies are
      needed to determine the conditions under which topical alpha-tocopheryl acetate
      and alpha-tocopheryl succinate enhance photocarcinogenesis.

PMID- 8875556
TI  - Disposition and metabolism of topically administered alpha-tocopherol acetate: a
      common ingredient of commercially available sunscreens and cosmetics.
AB  - Skin cancers are a serious health problem in the United States. One common method
      of skin cancer primary prevention is use of sunscreens. Research has been
      conducted to ascertain the role of active ingredients of sunscreen products in
      photoprotection and possible carcinogenesis. In contrast, little is known about
      the "other ingredients", listed or unlisted, on sunscreen product labels. One
      such ingredient is vitamin E. usually in the form of alpha-tocopherol acetate.
      Results of recent studies of skin carcinogenesis in an ultraviolet (UV) B mouse
      carcinogenesis model suggest that topically applied alpha-tocopherol acetate does
      not prevent and, under some conditions, enhances skin cancer development and
      growth, whereas the free unesterified from of alpha-tocopherol significantly
      reduces experimental UVB carcinogenesis. We have performed a Phase II cancer
      prevention study to evaluate whether topically applied alpha-tocopherol acetate
      is absorbed in human skin and metabolizes to the free or other forms. In this
      double-blind study, 19 men and women > 30 years of age who had at least three
      actinic keratoses on their forearms were randomly assigned to apply alpha
      tocopherol acetate (125 mg/g) or difluoromethylornithine cream to their arms
      twice daily for three months. Blood samples and photographs and punch biopsies of
      actinic keratoses were obtained before and at the end of the study (Month 4).
      Plasma and skin concentrations of free alpha-tocopherol, alpha-tocopherol
      acetate, and gamma-tocopherol were analyzed by high-performance liquid
      chromatography at Month 4. The results of this report focus only on data obtained
      from the 11 participants randomized to the alpha-tocopherol acetate arm of the
      study. Topically applied alpha-tocopherol acetate was substantially absorbed in
      skin, with no evidence of conversion within skin to its unesterified form (i.e.,
      free alpha-tocopherol). There was no evidence of systemic availability or
      biotransformation of topically applied alpha-tocopherol acetate. In summary, we
      have determined that alpha-tocopherol acetate is not metabolized to the free form
      of alpha-tocopherol in plasma or skin.

PMID- 8875557
TI  - Suppression of mouse skin papilloma by canthaxanthin and beta-carotene in vivo:
      possibility of the regression of tumorigenesis by carotenoids without conversion
      to retinoic acid.
AB  - Using mouse skin papilloma as a model system, we examined whether the
      antitumorigenic activity of carotenoids was related to their provitamin A
      activity. Oral administration of canthaxanthin (CX) or beta-carotene at 200
      mg/kg/day for 14 days significantly reduced the cumulative size of papillomas
      induced on the skin by 9,10-dimethyl-1,2-benzanthracene (p < 0.05), after the
      accumulation of these carotenoids in the tumors. The levels of a protooncogene, c
      myc, were simultaneously suppressed in papillomas in carotenoid-treated mice.
      Because CX cannot be converted metabolically to retinoids, these results
      suggested that CX directly inhibited the growth of papillomas. Neither the
      accumulation of retinoids nor the expression of a retinoic acid-inducible gene,
      retinoic acid receptor-beta, was found in papillomas of CX- and beta-carotene
      treated mice, suggesting that, like CX, beta-carotene might exert the tumor
      suppressing effect without being converted to retinoids. Thus a certain
      antitumorigenic activity of carotenoids appears not necessarily to require their
      provitamin A activity.

PMID- 8875558
TI  - Effects of the Bowman-Birk protease inhibitor on survival of fibroblasts and
      cancer cells exposed to radiation and cis-platinum.
AB  - The Bowman-Birk inhibitor (BBI) is a soybean-derived anticarcinogenic protease
      inhibitor with anti-inflammatory activity. To assess the possibility of utilizing
      BBI for alleviating the side effects associated with lung cancer radiation and
      chemotherapy, we have determined the effects of BBI and a soybean concentrate
      enriched in BBI (known as BBIC) on radiation- and cis-platinum-induced
      cytotoxicity in A549 human lung cancer cells. The results demonstrated that
      neither BBI nor BBIC protected A549 cells from radiation- and cis-platinum
      induced cytotoxicity. In fact, BBI and BBIC potentiated the cell-killing effects
      induced by cis-platinum alone, and BBIC treatment led to significantly enhanced
      cell killing by cis-platinum in combination with radiation treatment in the lung
      carcinoma cells. BBI conferred a significant protective effect onto mouse
      fibroblasts (10T1/2 cells) treated with cis-platinum in combination with 6 Gy of
      X-ray irradiation. These results suggest that BBI and BBIC, when given to lung
      cancer patients, are unlikely to interfere with cancer treatment utilizing
      radiation and cis-platinum.

PMID- 8875559
TI  - Anthropometric measures and risk of cancers of the upper digestive and
      respiratory tract.
AB  - Data from a case-control study on the upper digestive and respiratory tract
      cancers were analyzed to investigate the relationship with anthropometric
      measures. The data set included 538 oropharyngeal, 410 esophageal, and 388
      laryngeal cancer cases and 2,102 controls in hospital for acute nonneoplastic
      diseases, unrelated to tobacco or alcohol use, recruited in the same catchment
      areas as the cases. Lower body weight appeared to be an indicator of
      oropharyngeal and esophageal cancer and, more moderately, of laryngeal cancer.
      The multivariate odds ratio (OR) for oropharyngeal cancer was 5.0 for subjects in
      the lowest compared with the highest quartile of weight. The corresponding ORs
      were 6.2 for esophageal and 2.2 for laryngeal cancer. When quartiles of body mass
      index (BMI) were considered, the ORs in the lowest quartile were 4.0 for
      oropharyngeal, 6.3 for esophageal, and 2.4 for laryngeal cancer. Subjects in the
      lowest quartile of height had ORs of 2.0 for oropharyngeal, 1.6 for esophageal,
      and 1.4 for laryngeal cancer. When all the upper digestive and respiratory tract
      neoplasms were considered together, the OR for subjects with lower BMI who were
      also current smokers compared with never-smokers with higher BMI was 11.4. The OR
      was 5.0 for those consuming six or more drinks/day and with low BMI. Although the
      nature of the association needs to be clarified, these data suggest that leanness
      may be involved in the process of upper digestive and respiratory tract
      carcinogenesis.

PMID- 8875560
TI  - Glutathione inhibits experimental oral carcinogenesis, p53 expression, and
      angiogenesis.
AB  - Previous studies have shown that reduced glutathione (GSH) inhibits experimental
      oral carcinogenesis in the hamster buccal pouch model. To gain further
      understanding of molecular mechanisms in the anticancer effect of GSH, these
      studies examined levels of p53 protein expression. 7,12-Dimethylbenz[a]anthracene
      (DMBA) was applied to the buccal pouches of 20 Syrian Golden hamsters
      (Mesocricetus auratus) in a 0.5% solution in mineral oil thrice weekly for 14
      weeks. In 10 animals, 10 mg/kg reduced glutathione (GSH) in 0.5 ml of mineral oil
      was administered by mouth thrice weekly on days alternate to the DMBA painting.
      An additional 20 animals served as DMBA-untreated and GSH controls. At the
      termination of the experimental period, there were fewer tumors in the DMBA-GSH
      than in the DMBA tumor control group, and the tumors were smaller (tumor burden
      315 vs. 3,040 mm3). Histologically, the DMBA-GSH group showed a marked reduction
      in dysplasia, carcinoma in situ, and invasive epidermoid carcinoma sites.
      Immunohistochemically, by use of monoclonal antibodies for wild-type p53 (PAb
      246), changes were observed in protein expression levels at dysplastic sites and
      within the malignant tumors. Staining for p53 protein was slightly increased in
      dysplasia and squamous cell carcinoma in the tumor control animals (painted with
      DMBA) compared with the untreated controls that were free of tumors. In the GSH
      and DMBA treatment group, p53 protein expression levels were strongly increased
      in dysplastic and tumor sites. The significant inhibition of oral carcinogenesis
      associated with the administration of GSH was correlated with the increased
      levels of the wild-type p53 tumor suppressor gene, suggesting its possible use as
      a biomarker for GSH chemoprevention. The inhibition of oral carcinogenesis by
      reduced GSH was also related to a very significant inhibition of tumor
      angiogenesis, defined by factor VIII staining. Thus angiogenesis inhibition may
      be an additional mechanism for antioxidant chemoprevention, and this suggests
      another possible biomarker for antioxidant chemoprevention.

PMID- 8875561
TI  - RRR-alpha-tocopheryl succinate enhances TGF-beta 1, -beta 2, and -beta 3 and TGF
      beta R-II expression by human MDA-MB-435 breast cancer cells.
AB  - The proliferation of MDA-MB-435 human breast cancer cells was inhibited by RRR
      alpha-tocopheryl succinate (vitamin E succinate, VES). Conditioned media (CM)
      from VES growth-inhibited cells contained potent antiproliferative activity, part
      of which is contributed by transforming growth factor-beta (TGF-beta) isoforms.
      Antibody neutralization analysis, employing TGF-beta isoform-specific antibody
      reagents, showed that TGF-beta 1, -beta 2, and -beta 3 were present in the CM
      from VES-treated cells. Culturing MDA-MB-435 cells with VES did not alter the
      levels of constitutively expressed 2.4-kb TGF-beta 1, 3.0- and 4.0-kb TGF-beta 2,
      or 1.2- and 3.5-kb TGF-beta 3 mRNA transcripts. Inhibition of DNA synthesis by
      MDA-MB-435 cells was increased by combinations of suboptimal levels of VES and
      purified TGF-beta 1. VES-treated MDA-MB-435 cells exhibited enhanced binding of
      radiolabeled TGF-beta 1, and Western immunoblotting analyses showed that VES
      treatment enhanced TGF-beta type II receptor protein expression. TGF-beta type I
      receptor protein levels were not modified by VES treatments. Although the mRNA
      transcript for the 5.5-kb TGF-beta type II receptor was upregulated after four
      hours of treatment with VES, this treatment did not modify the 6.5-kb TGF-beta
      type I or the 6.5-kb TGF-beta type II receptor mRNAs. Results demonstrate that
      biologically active TGF-beta 1, -beta 2, -beta 3 and levels of TGF-beta type II
      receptor expressed by human breast cancer cells are enhanced by VES treatment.

PMID- 8875562
TI  - Rapid expulsion of the intestinal trematodes Echinostoma trivolvis and E. caproni
      from C3H/HeN mice after infection with Nippostrongylus brasiliensis.
AB  - The number of goblet cells in the small intestines of C3H/HeN mice increased
      rapidly following their infection with about 500 third-stage larvae (L3) of the
      intestinal nematode Nippostrongylus brasiliensis. The number of goblet cells
      reached its peak on day 9 postinfection (p.i.). Worm burdens in the hosts' small
      intestines were determined following a challenge infection with encysted
      metacercariae of the intestinal trematodes Echinostoma trivolvis or E. caproni on
      days 8 and 16 after primary infections with N. brasiliensis. All metacercariae of
      E. trivolvis or E. caproni used to challenge the hosts on day 8 p.i. were
      expelled. Considerable numbers of E. trivolvis (48.6%) and E. caproni (67.1%)
      remained in the intestines of hosts challenged with these echinostomes on day 16
      p.i. All the controls used for E. trivolvis and E. caproni infections without
      primary infections with N. brasiliensis showed recovery rates greater than 70%.
      An enzyme-linked immunosorbent assay (ELISA) showed that the IgM titer rose
      remarkably and plateaued on day 11 p.i. No marked rise in the IgG or IgA titer
      occurred during the experiment. These results indicate that mucins increased by
      hyperplastic goblet cells associated with primary infections with N. brasiliensis
      are responsible for a rapid expulsion of the worms of the challenge infection
      with E. trivolvis or E. caproni from the mouse host.

PMID- 8875563
TI  - Control of Oesophagostomum dentatum and Hyostrongylus rubidus in outdoor-reared
      pigs by daily feeding with the microfungus Duddingtonia flagrans.
AB  - An investigation of pasture-reared pigs experimentally infected with
      Oesophagostomum dentatum and Hyostrongylus rubidus showed that daily doses in the
      feed with the microfungus Duddingtonia flagrans over a 2-month period led to
      lowered herbage larval infectivity of both species. This was further
      substantiated by low worm recoveries in initially parasite-naive tracer pigs that
      were later introduced to the pasture plot. The control setup comprised the
      release of similarly infected but nondosed pigs on a plot of the same area,
      followed by a group of tracer pigs. This paper discusses the potentials for using
      this biological control principle in the pig industry and emphasizes the research
      required, primarily regarding production technology and elaboration of feasible
      epidemiology-based dosing regimens, before such control can be implemented in
      practice.

PMID- 8875564
TI  - Differentiation of Entamoeba histolytica and E. dispar DNA from cysts present in
      stool specimens by polymerase chain reaction: its field application in the
      Philippines.
AB  - It has been established that two distinct species exist within what was
      originally known as Entamoeba histolytica. These are E. dispar and E.
      histolytica, for the nonpathogenic and pathogenic forms, respectively.
      Differentiation of these two organisms is of great clinical importance since they
      are morphologically indistinguishable and both forms can infect the human
      intestinal cavity to different degrees. A simple and rapid DNA-extraction method
      that can be used directly on formalin-fixed stool specimens has been developed.
      The extracted DNA was used for the identification of the species existing in the
      stools by polymerase chain reaction (PCR). A total of 72 randomly collected stool
      samples from the Philippines were analyzed. In all, 19 samples reacted with E.
      dispar primers, resulting in the expected 101-bp PCR products; however, none
      reacted with E. histolytica primers. Furthermore, sensitivity assay suggests that
      genomic DNA from as few as five cysts can be used as a template for PCR. These
      observations imply that the use of genomic DNA directly extracted from formalin
      fixed stool specimens for PCR amplification is a useful tool for obtaining a
      sensitive and accurate diagnosis that can be applied even in epidemiology
      studies.

PMID- 8875565
TI  - Immunosuppression and inhibition of inflammation in mice induced by a small
      Taenia solium RNA-peptide to implanted T. solium metacestodes.
AB  - Subcutaneous implantation of Taenia solium metacestodes in mice induces an
      inflammatory reaction made up mainly of neutrophils and eosinophils after 12
      days. Administration of a small RNA-peptide (metacestode factor, MF) purified
      from T. solium metacestodes significantly reduces the inflammatory site in both
      size and composition, yielding a very low number of eosinophils. The metacestodes
      implanted in control mice were completely destroyed and their remnants were
      surrounded by an intense inflammation predominantly made up of neutrophils and
      eosinophils. In contrast, metacestodes implanted in mice treated with MF showed
      apparently intact suckers, rostellum, hooks, and tegument. Inhibition of
      inflammation around the parasites was also observed in mice immunized with T.
      solium metacestode antigens and inoculated simultaneously with MF. Mice immunized
      only with T. solium metacestode antigens produced a granulomatous process around
      metacestodes that destroyed most of the large metacestode structures: suckers,
      rostellum, hooks, and tegument-wall tissues. Furthermore, treatment of mice with
      MF or implanted metacestodes decreased the antibody (P < 0.05) and cellular
      responses (P < 0.05) to metacestode antigens. The antibody responses was even
      lower when both of these treatments were given simultaneously. These findings
      support the idea that MF plays a key role in the down-regulation of the host
      immune response, contributing to the parasite's survival.

PMID- 8875566
TI  - Influence of cytokines on Toxoplasma gondii growth in human astrocytoma-derived
      cells.
AB  - The effects of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF
      alpha), interleukin 1-alpha (IL-1-alpha), and interleukin 6 (IL-6) on the growth
      of the Toxoplasma gondii RH strain were studied in vitro using a human
      astrocytoma-derived cell line. Cells were treated with cytokines at different
      concentrations at 24 h prior to infection with T. gondii tachyzoites. IFN-gamma
      did not induce any modification in T. gondii growth, whatever the concentration
      used. TNF-alpha induced a significant decrease in the total number of
      tachyzoites, whereas IL-1-alpha surprisingly induced an increase in the number of
      tachyzoites. Our results show that the effects of cytokines on T. gondii growth
      may be of great importance in the control of cerebral toxoplasmosis but that they
      can vary, depending on the cell type considered.

PMID- 8875568
TI  - Malaria diagnosis: standardization of a polymerase chain reaction for the
      detection of Plasmodium falciparum parasites in individuals with low-grade
      parasitemia.
AB  - In Brazil, no study has been done concerning the detection of malaria parasites
      by polymerase chain reaction (PCR) related to the diagnosis of Plasmodium
      falciparum malaria. In the present report we describe a highly sensitive
      methodology for malaria diagnosis using a nested PCR method based on
      amplification of the p126 P. falciparum gene detected by simple ethidium bromide
      staining. The P. falciparum Palo Alto strain (culture samples) was serially
      diluted in blood from an uninfected donor to a final level of parasitemia
      corresponding to 10(-8)% and was processed for PCR amplification. In each of
      these dilutions a parasitological examination was performed to compare the
      sensitivity with that of PCR amplification. Blood samples (field samples) were
      obtained from 51 malarious patients with positive thick blood smears (TBS) who
      were living in endemic regions of the Brazilian Amazon. They corresponded to 42
      P. falciparum and 9 P. vivax cases, with parasitemia levels ranging from only 16
      to 20,200 parasites/microliter for P. falciparum disease and from 114 to 11,000
      parasites/microliter for P. vivax malaria. We demonstrate that the use of nested
      PCR allows the detection of 0.005 parasites/microliter without the use of
      radioactive material. The use of a 1-ml sample volume and the organic DNA
      extraction method should be suitable in blood banks and for the evaluation of
      patients during and after drug treatment.

PMID- 8875567
TI  - Cell-mediated immune response and T-like cells in thymectomized Oncorhynchus
      mykiss (Walbaum) infected with or vaccinated against the pathogenic
      haemoflagellate Cryptobia salmositica Katz, 1951.
AB  - T-cell-mediated delayed-type hypersensitivity (TDTH) reaction was detected in
      Cryptobia salmositica-infected intact and thymectomized (2 months post
      thymectomy) Oncorhynchus mykiss (Walbaum). Both groups of fish showed significant
      induration at the site of C. salmositica antigen injection at 8, 12 and 16 weeks
      post-infection. A significant difference was not observed in TDTH reactions
      between the thymectomized and intact (control) infected fish. The total numbers
      of circulating leucocytes detected in infected thymectomized fish were
      significantly lower than those found in infected shamthymectomized fish. The
      numbers of T-like cells determined (using alpha-naphthyl acid esterase assay) in
      thymectomized fish (9 months post-thymectomy) were similar to those seen in
      intact fish prior to and at 4 weeks after vaccination with an avirulent strain of
      C. salmositica. At 2 weeks after challenge with the pathogen the numbers of T
      like cells in intact vaccinated fish increased significantly (P < 0.01) and
      remained high for the duration of the study (15 weeks). However, in vaccinated
      thymectomized fish the numbers of T-like cells remained low after parasite
      challenge. These results suggest that thymectomy in adult rainbow trout did not
      lower T-cell-mediated delayed-type hypersensitivity; however, it reduced the
      numbers of circulating leucocytes and retarded the proliferation of T-like cells
      after antigenic stimulation.

PMID- 8875569
TI  - Free and bound biotin molecules in helminths: a source of artifacts for avidin
      biotin-based immunoassays.
AB  - The avidin-biotin molecular recognition system is widely used in parasite
      immunology. However, the presence of biotin and/or biotin-containing molecules
      (BCMs) in samples may lead to erroneous results. In the work reported herein we
      investigated the extent to which biotin and BCMs present in helminth extracts may
      interfere in avidin/biotin-based immunoassays and developed an enzyme-linked
      immunosorbent assay (ELISA) for quantification of these components. In avidin
      based ELISA using antinematode monoclonal antibodies, an extract of the nematode
      Anisakis simplex showed very high background reactivity due to biotin/BCMs,
      whereas the background reactivity in an extract of the nematode Trichinella
      spiralis was negligible. To investigate interspecies differences further, we
      performed Western-blot analyses (with avidin as the detector) of extracts from
      seven nematodes (A. simplex, Ascaris suum, Toxocara canis, Hysterothylacium
      aduncum, T. spiralis, and Trichuris muris) and the cestode Bothriocephalus
      scorpii. Even within superfamilies there was considerable variation in the
      banding patterns obtained. The above-mentioned results confirm that biotin and
      BCMs may be a significant source of interference in ELISA and immunoblotting, two
      of the techniques most widely used in parasitological immunodiagnosis. A
      competition ELISA designed to allow accurate quantification of biotin and BCMs in
      helminth extracts likewise indicated very considerable interspecies variation.
      Both A. simplex and H. aduncum had very high biotin/BCM contents. Microdialysis
      of extracts in the presence of dimethylsulfoxide to remove free biotin prior to
      ELISA indicated that the high biotin/BCM content of the H. aduncum extract (but
      not the A. simplex extract) was very largely due to free biotin. Taken together,
      these results indicate that extreme caution should be exercised in the use of
      avidin/biotin-based immunoassays for the detection of helminth antigens and that
      in many cases it may be better to use an alternative recognition system.

PMID- 8875570
TI  - Paramphistomum daubneyi and Fasciola hepatica: the redial burden and cercarial
      shedding in Lymnaea truncatula subjected to successive unimiracidial cross
      exposures.
AB  - The development of redial burden and cercarial shedding were studied in two
      groups of Lymnaea truncatula subjected to successive cross-exposures to one
      miracidium of Paramphistomum daubneyi and one of Fasciola hepatica per snail, or
      vice versa. The results were compared with those obtained in controls subjected
      to two unimiracidial exposures to the same trematode species. The infection rate
      was 61% in the group cross-exposed to P. daubneyi/F. hepatica and 37% in that
      cross-exposed to F. hepatica/P. daubneyi; it was 37% in the control group exposed
      to F. hepatica and 21% in that exposed to P. doubneyi. Snails harboring larval
      forms of both trematodes were few in number in cross-exposed groups and the
      redial burden was low, with one trematode dominating over the other. Free
      cercariae of F. hepatica and those of P. daubneyi were significantly more
      numerous at day 35 in the group cross-exposed to P. daubneyi/F. hepatica than in
      the controls or the other cross-exposed group. Mixed cercarial sheddings were
      obtained from 40% of snails with emission in the group cross-exposed to P.
      daubneyi/F. hepatica and from 21% of those in the F. hepatica/P. daubneyi group.
      The numbers of P. daubneyi metacercariae were significantly greater in the group
      cross-exposed to P. daubneyi/F. hepatica than in the other cross-exposed group,
      whereas no significant difference in mean numbers was noted for the F. hepatica
      cysts. Repartition of metacercariae over the patent period was clearly more
      irregular for P. daubneyi than for the other trematode.

PMID- 8875571
TI  - Relationship of the virulence of Trichomonas vaginalis and the major
      histocompatibility complex in murine trichomonad infection.
AB  - A biological assay based upon the induction of abscesses in mice injected
      subcutaneously with Trichomonas vaginalis was shown to be a valid method for
      comparing the virulence of two isolates of T. vaginalis cultured from two
      patients, one suffering from severe vaginitis and the other exhibiting only mild
      disease. The data showed excellent correlation between the physical dimensions of
      abscesses in mice injected with each trichomonad isolate and the severity of
      vaginitis produced in the women from whom the isolates were obtained. The assay
      employed in our study incorporated measurement of the mean abscess volumes from
      day 1 to day 6 post-inoculation with T. vaginalis. We found that the abscess
      assay was clearly superior to a murine intraperitoneal assay for virulence
      evaluation of trichomonad isolates. We then used the murine abscess assay to
      determine the susceptibility of different strains of mice to infection with a
      virulent T. vaginalis isolate so as to test whether the genetic constitution of
      the host would influence the pathogenesis of the disease. BALB/c (H-2d) mice were
      susceptible to infection with T. vaginalis, but both CBA/CaH (H-2k) and BALB/c-H
      2k mice were shown to be resistant. The quantitation of abscess formation in
      these inbred and congeneic resistant mouse strains demonstrates that the severity
      of infection with T. vaginalis is governed by genes mapping within the major
      histocompatibility complex.

PMID- 8875572
TI  - Allium sativum-induced death of African trypanosomes.
AB  - The effect of Allium sativum (Liliacea) on trypanosome-infected mice was
      examined. At a dose of 5.0 mg/ml, the oily extract from the pulp completely
      suppressed the ability of the parasites to be infective in the host. Column
      chromatography of the extract gave four fractions: ethylacetate/methanol,
      ethylacetate/ethanol, benzene/methanol, and acetic acid/methanol. Among these
      fractions, the acetic acid/methanol fraction retained the trypanocidal features
      of the crude extract. It cured experimentally infected mice of trypanosomiasis in
      4 days when given at a dose of 120 mg/kg per day. The extract also manifested
      inhibition of procyclic forms of Trypanosoma brucei brucei and phospholipases
      from T. congolense, T. b. brucei, T. vivax. The extract appears to be diallyl
      disulfide (DAD) and may interfere with the parasites' synthesis of membrane
      lipids.

PMID- 8875574
TI  - A preliminary study on the attenuation of Tunisian schizont-infected cell lines
      of Theileria annulata.
AB  - Four Theileria annulata cell lines were characterised at low passage levels using
      two polymorphic markers and then used to infect calves. Their virulence seemed to
      be related to the number of genotypes present within the cell line. In all, 3 of
      the 4 cell lines were cultured up to passage 100 or 200 and inoculated into
      calves. Their characterisation using the same markers indicated that the
      attenuation was related to a reduction in the parasite polymorphism down to a
      single genotype. The immunogenicity of the three attenuated cell lines was
      assessed in calves using two types of challenge. Optimal protection was observed
      against homologous challenges. The level of immunity to heterologous challenges
      appeared to decrease with attenuation and seemed to depend on the cell line used.

PMID- 8875573
TI  - Ultrastructure of the surface structures and electron immunogold labeling of
      peptide immunoreactivity in the nervous system of Pseudothoracocotyla indica
      (Polyopisthocotylea: Monogenea).
AB  - Transmission electron microscope studies of the tegument of the tropical marine
      fish monogenean parasite Pseudothoracocotyla indica describe surface
      specialisations and detail the ultrastructure of the tegument and the haptor. The
      tegument consists of a syncytium, numerous electron-dense granules, electron
      lucent vesicles and large multivesicular bodies. The posterior tegumental
      syncytium is infolded to form tegumental ridges that are present on both the
      ventral and dorsal surfaces. A thin coat of glycocalyx is present on the tegument
      surface. In contrast, the tegumental syncytium of the haptor is relatively thin,
      containing electron-dense granules and various-sized electron-lucent vesicles.
      Exocytosis of the electron-dense and electron-lucent vesicles apparently occurs
      in the syncytium of the haptor and general body surface. Tegumental damage was
      observed on the dorsal surface in the mid-body region and may possibly have been
      due to natural mechanical forces. The haptor consists of electron-dense clamp
      sclerites embedded within a matrix covered by the tegumental syncytium. The
      sclerites are connected to each other and to the basal lamina by radially
      oriented muscle fibres. The haptor is richly supplied with non-myelinated nerve
      axons. Both uniciliated and non-ciliated presumed sensory structures are present
      on the body surface and haptor. Uniciliated sensory structures were found mainly
      around the oral sucker. Groups of neurons and nerve processes containing
      neurosecretory vesicles were frequently observed in the vicinity of the clamps.
      Electron immunogold labelling studies demonstrated that neuropeptide F [NPF
      (Moniezia expansa)] immunoreactivity was confined to electron-dense-cored
      neurosecretory vesicles in nerve fibres from the posterior and haptor regions of
      the fluke.

PMID- 8875575
TI  - The stage-conversion time of Toxoplasma gondii: interpretation of chemical
      biologic data out of parasitologic or host context.
AB  - Several published biologic times for the stage conversion of Toxoplasma gondii
      from tachyzoite to bradyzoite in mice are critically examined. There are several
      reports of 3 days and many of longer times. Possible errors, related to delay
      from dissemination of the infection, are pointed out. The time to the appearance
      of the 36-kDa surface antigen, sometimes used for the diagnosis of bradyzoites,
      should be compared with the biologic attribute of bradyzoites, inducing the short
      prepatent period in cats. It is recalled that the development of acid pepsin
      resistance is not exclusively correlated with the biologic definition of
      bradyzoites. Reactivation of toxoplasmosis in mice does not necessarily follow
      the administration of a corticosteroid. The daily dose, the type of
      corticosteroid, its solubility, whether alcohol or ester, the route of
      administration, the host, and, probably, other factors are important in giving
      rise to sufficient immunosuppression for reactivation to occur. The plea is made
      to examine biologic measurements in the context of parasitologic and host
      factors.

PMID- 8875576
TI  - Pediatric thoracoscopy.

PMID- 8875577
TI  - From laboratory to the "field".

PMID- 8875578
TI  - Diagnosis of interstitial lung disease.

PMID- 8875579
TI  - Is a CT guided needle better than a knife?

PMID- 8875580
TI  - The six-minute walking test in children with cystic fibrosis: reliability and
      validity.
AB  - There is a need to judge general exercise tolerance in children with cystic
      fibrosis (CF) under normal daily activity conditions and -when more extensive
      testing is required-in an exercise laboratory in a specialized center. We
      investigated the reproducibility, validity, and criterion for a 6-minute walking
      test, which simulates normal childhood activities. In Part A, we evaluated the
      reproducibility of a 6-minute walking test in 23 children (12 girls and 11 boys;
      ages 11.1 +/- 2.2 years; range, 8.2 15.6 years) with mild symptoms of CF [forced
      expiratory volume in 1 second (FEV1) 94.4 +/- 16.5% of predicted values (range,
      60.6-129.7); body weight Z-score -0.71 +/- 0.81 (range, -1.73-0.93)]. The
      subjects performed two standardized 6-minute walking tests with 1 week between
      tests. There was no significant difference between the two walking distances
      reached (737 +/- 85 versus 742 +/- 90 meters; P = 0.56), and there was a strong
      correlation between the two walking distances reached by the individuals (r =
      0.90, P < 0.0001). In Part B, the validity of the walking test was evaluated in
      15 children (6 girls and 9 boys; ages 14.5 +/- 2.0 years; range, 10.2-16.9 years)
      with moderate symptoms of CF [FEV1 = 58 +/- 16.0% of predicted values, (range,
      41.1-89.4); RV/TLC ratio = 46.3 +/- 6.5% (range, 31.6-57.2); body weight Z-score:
      -1.29 +/- 0.60 (range, -2.20-0.14)]. They underwent standardized maximum
      incremental exercise testing on a cycle ergometer and a 6-minute walking test.
      Postexertional lactate values exceeded threshold values (as described in the
      literature) in all patients but one. Correlation analysis (Pearson) showed a
      significant correlation between the walking distance reached (WD = 697 +/- 104
      meters), and the maximum workload (Wmax = 118 +/- 44 watt; r = 0.76, P < 0.001)
      or the maximum oxygen uptake (1,688 +/- 495 ml; r = 0.76, P < 0.001), the latter
      two being determined on a cycle ergometer, RV/TLC% showed a significant negative
      correlation (r = -0.72, P < 0.01) with WD. Stepwise multiple regression analysis
      showed a multiple regression coefficient of R = 0.84 (P < 0.001) for Wmax and
      RV/TLC % as the independent variables vs. WD as the dependent variable. We
      conclude that the 6-minute walking test is a valid and useful test in children
      with mild to moderate symptoms of CF to assess their exercise tolerance and
      endurance. Exercise test results correlated negatively with pulmonary
      hyperinflation expressed by the RV/TLC ratio.

PMID- 8875581
TI  - Anabolic effect of biosynthetic growth hormone in cystic fibrosis patients.
AB  - The purpose of this study was to determine whether GH treatment of cystic
      fibrosis (CF) patients can result in an anabolic effect, i.e., increased weight
      gain, improved growth rate, nitrogen retention, and improved pulmonary function.
      Nine prepubertal endocrinologically normal CF patients (3 girls, 6 boys;
      chronological age (CA) 5.5-9.8 years, and bone age (BA) 4.5-9.0 years), received
      recombinant human growth hormone (rhGH) 0.3 mg/kg/week subcutaneously for a
      period of 12 months (N = 8) or 9 months (N = 1). Normal glucose tolerance was
      determined before treatment. Pulmonary function studies and anthropometric
      measurements were done every 3 months. Thyroid status, somatomedin C (SmC), BA,
      and routine chemistries were evaluated every 6 months. The pretreatment growth
      velocity averaged 5.7 +/- 0.3 (SE) cm/year and significantly increased to 7.8 +/-
      0.4 (SE) cm/year during therapy, (P < 0.01). Standard deviation scores (SDS) for
      height significantly increased during rhGH therapy as compared with pretreatment,
      (P < 0.05). Weight of the patients during rhGH therapy did not significantly
      change during or after rhGH therapy. After therapy, all patients showed a
      significant increase in arm muscle area (AMA) and a significant decrement in arm
      fat area (AFA) (P < 0.01). Net nitrogen anabolism was negative in all subjects
      before therapy but became more positive in five patients during rhGH therapy.
      Three patients achieved positive nitrogen retention. SmC values significantly
      increased from a mean value of 0.62 +/- 0.1 (SE) U/ml to 1.6 +/- 0.6 (SE) U/ml
      after therapy. BA advanced 1.0 +/- 0.1 SE per year after treatment. Of the seven
      patients able to perform adequate pulmonary function testing, improvement
      occurred in FVC, FEV1.0, and PEFR in 5, 5, and 4 patients, respectively, but
      these changes did not reach statistical significance. We conclude that
      biosynthetic rhGH therapy had a significant anabolic effect in CF patients as
      shown by increased growth velocity, SmC values, increased protein and decreased
      fet stores, and a positive or less negative net nitrogen retention in five of the
      patients.

PMID- 8875582
TI  - Consequences of hypogammaglobulinemia and steroid therapy in severe
      bronchopulmonary dysplasia.
AB  - We retrospectively studied the relation between corticasteroid therapy,
      hypogammaglobulinemia (HG), and recurrent infections in 37 infants with moderate
      to severe bronchopulmonary dysplasia (BPD). Nineteen of the 37 patients had
      tracheostomies because of chronic respiratory failure. We hypothesized that
      recurrent infections were most prevalent in infants whose IgG levels remained low
      at one year of age (persistent HG) and in infants receiving high doses of
      corticosteroids during the first year of life. We further hypothesized that the
      duration of HG was strongly correlated with the cumulative first year steroid
      dose. We also studied the response to intravenous gammaglobulin (IVIG)
      replacement therapy in this population of BPD infants. Our results showed an
      association between first year corticosteroid dose, duration of HG (r = 0.49, p <
      0.003), and frequency of infections (r = 0.51, p < 0.001). We noted a relatively
      strong correlation between frequency of infections and duration of HG (r = 0.84,
      p < 0.0001). Twenty-four of 37 (65%) infants showed persistent HG and 49% had
      evidence of abnormal specific antibody production. Sixty-four percent of infants
      studied had reduced lymphocyte responsiveness to mitogen stimulation. Nineteen of
      37 (51%) infants required IVIG for an average duration of 17.9 months due to
      recurrent infections. The average number of infections per year decreased from
      10.6 to 2.8 (t = 12.32, p < 0.0001). There were no complications associated with
      IVIG therapy, but one infant died of bronchiolitis obliterans following heart
      lung transplantation. Eight of 37 (22%) infants have persistent immunologic
      dysfunction requiring ongoing IVIG at four years or more of follow-up. We
      conclude that a substantial number of ill infants with BPD will have immune
      dysfunction characterized by persistently low IgG levels and reduced specific
      antibody responsiveness to protein antigens. We speculate that these findings are
      related to the cumulative dose of corticosteroids received in the first year of
      life and to the severity of underlying disease.

PMID- 8875583
TI  - Polysomnographic studies in children with adenotonsillar hypertrophy and
      suspected obstructive sleep apnea.
AB  - Upper airway obstruction causes many sleep-related respiratory disorders that can
      culminate in obstructive sleep apnea syndrome (OSAS). Polysomnography is
      routinely used to define OSAS in adults, but problems remain in diagnosing
      children by this method. The current study was designed to analyze the
      polysomnographic patterns in children with symptomatic adenotonsillar hypertrophy
      and to determine whether obstructive respiratory events shorter than 10 sec could
      have pathophysiological significance. Furthermore, we analyzed the correlation
      between clinical data on children with adenotonsillar hypertrophy and
      polysomnographic findings. Twelve children (mean age, 4.5 +/- 1.5 years) with
      airflow obstruction due to adenotonsillar hypertrophy were observed in our Sleep
      Laboratory. Prior to study, a questionnaire was used to score symptom severity.
      Overnight polysomnography was then performed to measure total sleep time, sleep
      efficiency, desaturation index, minimal arterial oxygen saturation (SaO2),
      apneahypopnea (AH) episodes < or = 5 sec and those > or = 10 sec, and AH index,
      AH percentage of total test time, and number of spontaneous and respiratory event
      associated desaturations were recorded. Respiratory events of 5 sec or longer
      resulted in increases in the AH index and an increase in the number of
      oxyhemoglobin desaturations due to respiratory events. A significant relationship
      was found between the AH index and AH episodes > or = 5 sec and > or = 10 sec.
      There was, however, no association between polysomnographic parameters and
      symptom severity scores. An appraisal of AH recordings > or = 10 sec showed that
      desaturation episodes were more frequent than respiratory events, and the
      desaturation index was closely related to spontaneous and respiratory event
      associated desaturations. When considering all obstructive episodes > or = 5 sec,
      the number of desaturations did not exceed the number of respiratory events. The
      correlation between the desaturation index and spontaneous or respiratory event
      associated desaturations was similar. The occurrence of short AH episodes that
      lead to hemoglobin desaturation are important in the evaluation of OSAS in
      children.

PMID- 8875584
TI  - Dose response to inhaled terbutaline powder and peak inspiratory flow through
      Turbuhaler in children with mild to moderate asthma.
AB  - The purpose of this study was to investigate the relative effectiveness of 0.25
      mg, 0.5 mg, and 1.0 mg of terbutaline, administered via Turbuhaler, in children
      with mild to moderate asthma, and to register peak inspiratory flow rates through
      Turbuhaler (PIFTBH). Thirty-seven children in Portugal (one center) and 45
      children in Sweden (one center) aged 3-10 years participated in two separate,
      double-blind, placebo-controlled, crossover, and randomized studies of the same
      design. Because of differences in other therapies for asthma and climate,
      combination of the two studies into one metanalysis did not appear appropriate.
      The children inhaled 0.25 mg, 0.5 mg, and 1.0 mg terbutaline sulfate and placebo
      t.i.d. for consecutive 2-week periods without washout periods. Peak expiratory
      flow rates (PEF) were measured at home before and 15 minutes after each
      inhalation in the morning, afternoon, and evening. PIFTBH was measured twice at
      each of four clinic visits. At the Portuguese center the increases in mean
      morning PEF from before to after inhalation were 32 L/min after 0.25 mg, 35 L/min
      after 0.5 mg, and 40 L/min after 1.0 mg. The corresponding figures in Sweden were
      26 L/min, 31 L/min, and 29 L/min after 0.25 mg, 0.5 mg, and 1.0 mg, respectively.
      For children 3-6 years, mean values for PIFTBH were 60 L/min in Portugal (n =
      15), and 58 L/min in Sweden (n = 23). In the 7-10 year group the mean PIFTBH was
      72 L/min (n = 22) in Portugal, and 68 L/min (n = 22) in Sweden. We conclude that
      inhalation of terbutaline sulfate via Turbuhaler at a small dose of 0.25 mg
      resulted in good bronchodilation and was comparable to inhalations of 0.5 mg and
      1.0 mg in children aged 3-10 years with mild to moderate asthma. PIFTBH were
      comparable to values previously recorded in healthy 6-year-old and older children
      and in adult asthmatic patients.

PMID- 8875586
TI  - A new microtransducer catheter for measuring esophageal pressure in infants.
AB  - Measurement of esophageal pressure, as a reflection of pleural pressure, is
      essential for assessment of dynamic lung mechanics in neonates and infants.
      Conventionally, an esophageal balloon or a fluid-filled catheter is used, but
      considerable skill is required to obtain accurate results. Both devices have
      problems, and failure to achieve valid occlusion tests have been reported,
      particularly in small infants with lung disease. Recently, a flexible #3 French
      gauge (FG) microtransducer catheter (MTC, Drager Netherlands) has become
      available for medical monitoring. We have assessed the accuracy and feasibility
      of using this device for measuring lung mechanics in 51 spontaneously breathing
      infants and small children aged 1 day to 24 months (weight 1.35 to 12.0 kg), 9 of
      whom were healthy neonates, the remainder suffering from a variety of cardio
      respiratory diseases, and in 18 sick ventilated infants (weight 0.6 to 4.0 kg).
      Positioning of the catheter was well tolerated by all infants. The ratio of
      esophageal to airway opening pressure changes (delta Pes:delta Pao) ranged from
      0.94 to 1.09 [mean (SD) 1.013 (0.03)] for the spontaneously breathing infants and
      from 0.98 to 1.06 [mean (SD) 1.003 (0.02)] In the ventilated infants with no
      significant difference in this ratio between the two groups (p = 0.16). This new
      generation of catheter tip pressure transducers may provide a simpler and more
      reliable tool for assessing transpulmonary pressure changes in infants than has
      previously been available.

PMID- 8875585
TI  - Combined percutaneous lung biopsy and high-resolution computed tomography in the
      diagnosis and management of lung disease in children.
AB  - Computed tomography-guided percutaneous lung biopsy is a well-recognized
      procedure for obtaining tissue for diagnosis in adults with interstitial lung
      diseases. Recently this methodology has been extended to pediatric practice. We
      have further refined this technique by employing high-resolution computed
      tomography (HRCT) under general anesthesia to obtain maximum anatomical detail.
      High-quality images are obtained that accurately define the extent of disease,
      and percutaneous biopsies are then taken from a suitable area of radiological
      abnormality using an 18G Monopty needle. Twenty-six investigations have been
      performed on 24 patients. The diagnosis was established from 14 biopsies, and
      histological and/or radiological information that contributed to patient
      management was obtained from a further 4 procedures. In 4 patients the
      histological findings were inconclusive, and the final diagnosis was only
      confirmed by open lung biopsy and/or other investigations. The procedure was
      generally well tolerated, although chest drainage for pneumothorax was required
      in two patients. HRCT-guided percutaneous lung biopsy is a useful initial
      approach to the diagnosis of interstitial lung disease in selected patients; the
      necessity of more invasive procedures such as open, thoracoscopic, or
      transbronchial lung biopsy can thus generally be avoided.

PMID- 8875587
TI  - Humidification of oxygen with unheated humidifiers in tropical climates.
AB  - In developing countries, oxygen therapy in hospitals is frequently humidified
      with unheated bubble-through humidifiers. We assessed the efficacy of
      humidification under such circumstances. The water temperature in the humidifier
      and the ambient air temperature were measured and compared to the oxygen flow
      rate. It was calculated that oxygen was cooled in the humidifier by 6.12 degrees
      C (95% CI: 5.88; 6.35) per liter of flow for flow rates up to 2 l/min. Using the
      average temperatures on the hospital ward in January and August, and the WHO
      recommended flow rates of 0.5 l/min and 1 l/min, the relative humidity of the
      oxygen delivered to a child was estimated to be between 34% and 56%. We conclude
      that unheated bubble-through humidifiers achieve low humidity in oxygen in
      tropical climates. Some of the complications associated with the use of
      nasopharyngeal catheters for the delivery of oxygen might be explained by this,
      as oxygen of low humidity and temperature is delivered directly into the
      posterior nasopharynx.

PMID- 8875588
TI  - Pediatric thoracoscopy: a new vista.

PMID- 8875589
TI  - Optimized preparation of deca(L-alanyl)-L-valinamide by 9
      fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis on polyethylene glycol
      polystyrene (PEG-PS) graft supports, with 1,8-diazobicyclo [5.4.0]-undec-7-ene
      (DBU) deprotection.
AB  - Deca(L-alanyl)-L-valinamide is known to be a challenging model target for
      solidphase peptide synthesis, due to its hydrophobicity and its tendency to form
      secondary structures which inhibit acylation and deprotection. Here we report
      systematic studies on the synthesis of this peptide on an automated continuous
      flow instrument, using the 9-fluorenylmethyloxycarbonyl (Fmoc) group for N alpha
      amino protection and a polyethylene-glycol polystyrene (PEGPS) graft support. The
      optimal deprotection reagent proved to be DBU-piperidine-DMF (1:1:48,
      vol/vol/vol). The synthetic peptides were analyzed and characterized by high
      performance liquid chromatography and several mass spectrometric techniques.

PMID- 8875591
TI  - Mass spectrometric sequencing of synthetic peptides containing alpha, alpha
      dialkylated amino acid residues by MALDI post-source decay analysis.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS), a method well-suited for mass determination of biomolecules, has
      been used to analyze fragment ions generated by post-source decay (PSD) of
      synthetic peptaibols containing high proportions of the sterically hindered amino
      acids alpha-amino isobutyric acid (Aib) and isovaline (Iva). Since peptaibols do
      not have a free N-terminal amino group or side chains subject to protonation, the
      analyzed peptides saturnisporin SA III, trichotoxin A-50 and chrysospermin B were
      shown to provide preferred N-terminal and C-terminal a, b, and y fragments as
      sodium adduct. Additionally, a cleavage of the labile Aib-Probond was observed
      for all peptides investigated. The fragmentation pattern allowed confirmation of
      the primary structure and, therefore, demonstrated the usefulness of MALDI-PSD
      mass spectrometry for sequence analysis of the peptaibols.

PMID- 8875590
TI  - Syntheses and biological activities of parallel and antiparallel homo and hetero
      bis-cystine dimers of oxytocin and deamino-oxytocin.
AB  - New methods have been developed for the synthesis of disulfide-bridged homo and
      hetero peptide dimers (both parallel and antiparallel), as exemplified in the
      oxytocin and deamino-oxytocin families. The linear sequences were assembled by 9
      fluorenyl-methyloxycarbonyl (Fmoc) solid-phase synthesis techniques, with
      orthogonal protection for the two beta-thiols by appropriate combinations of S
      [(N'-methyl-N'-phenylcarbamoyl)sulfernyl] (Snm), S-acetamido-methyl (Acm) and S
      2, 4, 6-trimethoxybenzyl (Tmob) groups. Two octapeptide-resins gave rise to four
      different nonapeptide amides, which were brought together in defined ways to
      provide access to four of the six possible dimeric products. For each dimer, the
      first disulfide bond was formed in solution by a directed method, and then the
      second disulfide bond was formed, without purification of the intermediates, by
      iodine oxidation. Final isolated yields of the desired pure dimers were in the
      20% to 40% range. Biological activities ranged from 0.2% to 6% that of oxytocin,
      depending on the assay, and were in some cases considerably protracted. These
      data are consistent with the hypothesis that dimers revert slowly to monomers
      under the testing conditions.

PMID- 8875592
TI  - Tandem use of PCR and synthetic peptides to map helper T-cell epitopes on 27-kDa
      sexual stage antigen of Plasmodium falciparum.
AB  - Monoclonal antibodies recognizing two overlapping linear epitopes (amino acid
      residues 10 to 25) on the 27-kDa sexual stage antigen of Plasmodium falciparum
      (Pfg 27) effectively reduce the infectivity of the parasites to mosquitoes.
      Although malaria transmission-blocking immunity is largely antibody-mediated, T
      cells play critical roles in the regulation of antibody-secreting B cells. In
      order to facilitate the development of a malaria transmission-blocking subunit
      vaccine, studies were undertaken to map epitopes on Pfg 27 recognized by T-helper
      lymphocytes. Pfg27-specific T-cell hybridoma clones were produced from rPfg27
      immunized BALB/c (H-2d) and C57BL/6 (H-2b) mice, and used in studies to map
      antigenic determinants using PCR-generated Pfg27 gene fragments expressed in E.
      coli and synthetic peptides based on the Pfg27 sequence. We identified and mapped
      five distinct T-cell epitopes that are recognized by major histocompatibility
      complex (MHC) class II-restricted T-cell hybridoma clones. A single peptide (21
      residues) was shown to contain two tandem or partially overlapping epitopes
      recognized by T-cell hybridomas in the context of I-Ad and I-Ab, respectively.
      Synthetic peptides representing epitopes recognized by T-cell hybridoma clones
      elicited strong IgG responses in immunized mice, suggesting that T-cells of the
      helper phenotype were stimulated in vivo by these peptides. These studies
      represent the first detailed T-cell epitope analysis of a malaria sexual-stage
      antigen.

PMID- 8875593
TI  - Comparison of the immune response elicited by a free peptide and a lipopeptide
      construct.
AB  - Among the synthetic peptides derived from the 28-kDa Schistosoma mansoni
      gluthatione-S-transferase (Sm28GST), the C-terminal peptide, comprising amino
      acid residues 190 to 211, represents a major T-cell epitope in both infected
      humans and Sm28GST-immunized mice. The aim of this study was to determine the
      nature of the immune response induced by the 190-211 peptide coupled to a fatty
      acid (lipopeptide construction) in comparison to the free form. We explored B-
      and T-cell responses elicited by these two peptidic constructions in three
      different mouse strains (BALB/c, CBA/N and C57B1/6). For all strains, the
      addition of a lipid chain to the 190-211 peptide greatly modified its
      immunogenicity. The lipopeptide, compared to the free form, induced a greatly
      reduced antibody response against the peptide, whereas the production of
      messenger for cytokines was greatly increased after immunization with the
      lipopeptide. Immunization with peptide led mainly to a Th1-type cytokine profile
      following antigenic restimulation in vitro, while lipopeptide, in general,
      induced a mixed profile, and that occurred most significantly with the production
      of messengers for the protective cytokines IFN-gamma and IL-2, even without
      antigenic restimulations. This modification of immunogenicity of a peptide by the
      addition of a lipid chain could be of value in the development of efficient
      peptide vaccines.

PMID- 8875594
TI  - Sandostatin labeled with 99mTc: in vitro stability, in vivo validity and
      comparison with 111In-DTPA-octreotide.
AB  - Sandostatin, a synthetic octapeptide analog of a native hormone somatostatin, was
      labeled with a commonly available, inexpensive radionuclide, 99mTc, and evaluated
      for its suitability for in vivo imaging. Labeling was accomplished by reduction
      of the cystine bridge, which provided two sulfhydryl groups for chelation with
      99mTc. The complex was examined for thermodynamic stability in vitro and in
      experimental animals. Receptor specificity of the complex was determined using
      rat brain cortex membrane rich in somatostatin receptors, and its tissue
      distribution was studied in nude mice bearing human prostate cancer. In these
      studies, 99mTc-labeled oxytocin, a nonspecific peptide with similar molecular
      weight, served as a control and 111In-DTPA-octreotide served as a standard. The
      labeling method was simple, did not require protecting and deprotecting
      functional groups and yields were high (ca. 70%). The in vitro and in vivo
      stability was excellent, and Kd values were in the nanomolar range, similar to
      those of 111In-DTPA-octreotide. At 24 hours post-injection, the tumor uptake for
      99mTc-Sandostatin, expressed as percent of injected dose per gram (% ID/g), was
      higher, but the tumor/blood and tumor/muscle ratios were lower than those for
      111In-DTPA-octreotide. This agent, with its improved target-to-nontarget ratios,
      should prove to be of value for imaging somatostatin receptor-positive tumors.

PMID- 8875596
TI  - Nimodipine does not increase cerebral blood flow during subarachnoid hemorrhage
      in the rat.
AB  - The purpose of this study was to determine the effects of nimodipine, a calcium
      antagonist, on regional cerebral blood flow (CBF) in experimental subarachnoid
      hemorrhage (SAH) rats. Regional CBF was measured by the radioactive microspheres
      method. Experimental SAH was induced by a single injection of autologous arterial
      blood (0.3 ml) into the cisterna magna in anesthetized rats. Rats subjected to
      SAH showed an immediate and marked reduction of CBF in all brain regions
      throughout the experimental period. The infusion of nimodipine (1
      microgram/kg/min) was started 30 min before the induction of the experimental SAH
      and continued during the experiments. Nimodipine did not prevent the reduction of
      regional CBF after SAH. It is concluded that nimodipine only increases regional
      CBF in normal animals, but dose not affect the reduction of CBF after
      experimental SAH.

PMID- 8875595
TI  - Improved performances of spot multiple peptide synthesis.
AB  - We have developed a new software for the design of peptides to be prepared by the
      manual Spot synthesis method. It covers most of the common protocols for epitope
      mapping and offers flexibility for planning the experiment. We have also
      quantified the coupling efficiencies of three different coupling methods for the
      synthesis of four model decapeptides. The DIC/HOBT procedure was superior (mean
      coupling yield per cycle: 87% to 91%) to methods using pentafluorophenyl esters
      of Fmoc amino acids. All four peptides prepared by the three different coupling
      protocols were reactive with their cognate monoclonal antibody. Finally, using
      the best coupling method, we synthesized peptides of increasing length (10 to 29
      residues) bearing the model epitope AcPGK at the N terminus and showed that
      peptides of up to 29 residues were immunoreactive.

PMID- 8875598
TI  - Pharmacological characteristics of BDTI, a new isoquinoline-derived beta 2
      adrenoceptor agonist, in canine trachea and rat heart.
AB  - The tracheal relaxing effects and beta 2-selectivity of BDTI (1-benzyl-6,7
      dihydroxy-1,2,3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea
      and rat heart by radioligand binding assay and pharmacological experiments in
      comparison with those of other beta-adrenoceptor agonists, salbutamol and
      isoprenaline. The potency of relaxing effect on carbachol-induced contraction in
      isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 +/- 0.08) >
      BDTI (6.11 +/- 0.06) approximately salbutamol (6.14 +/- 0.08). ICI-118,551 (a
      selective beta 2-antagonist) and atenolol (a selective beta 1-antagonist)
      inhibited the relaxant action of BDTI with pKB values of 8.4 and 5.3,
      respectively, corresponding to high affinity for ICI-118,551 and low affinity for
      atenolol in antagonizing this response. The Kd values of radioligand ([3H]
      CGP12177) were 453.3 +/- 30.8 and 563.4 +/- 96.7 pmol/l in cultured canine
      tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and
      the Bmax values were 64.6 +/- 10.7 and 245.7 +/- 44.5 fmol/mg protein,
      respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]
      CGP12177 in a concentration-dependent manner in cultured canine TSMCs (Ki 0.73 +/
      0.15, 0.75 +/- 0.21 and 0.24 +/- 0.05 mumol/l, respectively) and rat
      cardiomyocytes (Ki 2.76 +/- 0.36, 2.31 +/- 0.26 and 0.22 +/- 0.03 mumol/l,
      respectively). These results demonstrated that BDTI possessed moderate
      selectivity (3.8-fold) to beta 2-adrenoceptors as judged from the Ki (heart)/Ki
      (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and
      salbutamol also stimulated cAMP formation in a concentration-dependent manner in
      cultured canine TSMCs (EC50 0.5 +/- 0.2 and 0.4 +/- 0.1 mumol/l, respectively)
      and rat cardiomyocytes (EC50 6.2 +/- 0.5 and 5.7 +/- 0.6 mumol/l, respectively).
      The selectivity of BDTI and salbutamol for beta 2-adrenoceptors on the cAMP
      response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a
      beta 2-selective adrenoceptor agonist.

PMID- 8875597
TI  - Chlorpromazine and diltiazem effects in muscle: blockage of acetylcholine-evoked
      contractures, membrane currents and tracer calcium uptake.
AB  - Contractures evoked by 0.1 mmol/l acetylcholine (ACh) in bundles from mouse
      soleus muscles denervated for 3-7 days were partly inhibited for more than 1 h
      following 2- to 10-min exposure to 10-100 mumol/l chlorpromazine (CP). The effect
      was stronger in sucrose than in Na+ solutions. A prolonged ACh-contracture
      blockage by diltiazem (20 mumol/l) was found only in the sucrose solution.
      Membrane currents evoked by ACh in the absence of Na+ were blocked by both the
      drugs, but recovered to more than 60% within 1 min of drug washout. ACh-evoked
      retention of tracer 45Ca2+ was decreased by more than 90 or 70% when CP or
      diltiazem, respectively, were applied and washed away 10 min before addition of
      45Ca2+ and ACh. The results suggest that the prolonged contracture blockage was
      not related to the blockage of ionic currents through the ACh-receptor channel
      but to a drug-induced loss of Ca(2+)-storing capacity.

PMID- 8875599
TI  - Effects of aldosterone and spironolactone on the isolated perfused rat heart.
AB  - Aldosterone antagonists are used in the treatment of hypertension. However, the
      cardiac influences of aldosterone and its antagonists have not been thoroughly
      investigated. In the present study, we investigated the effects of aldosterone
      and spironolactone on an isolated rat working heart model. Aldosterone (10(-8)
      mol/l) decreased the coronary flow and increased aortic flow and cardiac output.
      Spironolactone (10(-5) mol/l) inhibited these effects. These results suggest that
      aldosterone directly influences the cardiac function. Spironolactone appears able
      to inhibit the adverse cardiac effects of aldosterone. The exact mechanisms
      remain to be elucidated, but the early effects of aldosterone under our
      experimental conditions on the functional parameters of the heart suggest a
      nongenomic response including activation of receptors different from those
      transmitting genomic steroid actions.

PMID- 8875600
TI  - Transcytosis of lipid microspheres by human endothelial cells.
AB  - Human endothelial cells were cultivated on microporous membranes mimicking the
      luminal and basal spaces of blood vessels. When fluorescence-labeled lipid
      microspheres (LM) were added to the upper chambers of the model cultures,
      confluent monolayers of endothelial cells transported considerable levels of
      fluorescence to lower chambers. The transport was time dependent and was
      diminished by the addition of cytochalasin B. The uptake of LM into the
      endothelial cytoplasm was confirmed by electron microscopy and laser scanning
      confocal imaging. The amounts of fluorescence in the lower chamber were reduced
      when the endothelial cell layer was fixed with formaldehyde. These observations
      suggest that endothelial cells can transport LM by transcytosis. Endothelial
      cells seem to carry the LM without processing, since only minimal amounts of free
      fluorescence were detected even after longer cultivation periods. The
      fluorescence in the lower chambers of cell cultures treated with interleukin 1
      beta was 3.7-fold higher than that of untreated cells; interleukin 2 and tumor
      necrosis factor alpha treatments had no discernible effect on LM transport. The
      interleukin 1 beta induced increase of transcytosis in endothelial cells would
      explain why LM preferentially accumulate in inflammatory tissues.

PMID- 8875601
TI  - Characterization of CCKA receptor mediated pepsinogen secretion in porcine chief
      cells.
AB  - Cholecystokinin octapeptide (CCK-8s) is an endogenous stimulus of gastric
      pepsinogen secretion. Previous studies with isolated guinea pig chief cells
      indicated that this process is mediated through the CCKA receptor subtype, with
      an additional contribution from CCKB receptors. For comparison, we examined the
      mechanism of CCK-8s stimulated pepsinogen secretion in a larger nonrodent
      species, using highly enriched porcine chief cells as a functional in vitro
      model. Porcine chief cells responded weakly to stimulation by CCK-8s alone, but
      the efficacy was markedly enhanced in the presence of 10 mumol l-1 forskolin.
      Under these conditions, pepsinogen secretion was potently stimulated by CCK-8s
      and the CCKA receptor selective heptapeptide, A-71,378 (EC50 = 4.7 and 33 nmol l
      1), but not by CCKB receptor selective agonists. The prototype CCKA receptor
      selective antagonist L-364,718 blocked pepsinogen secretion with approximately
      2,000-fold higher affinity than the CCKB receptor selective analogue, L-365,260.
      This functional profile was consistent with the affinity rank order of all tested
      compounds at CCKA-receptor-like [125I]-BH-CCK-8s binding sites in the porcine
      gastric mucosa. Comparison with cloned CCKA receptors from other species revealed
      that the receptors mediating pepsinogen secretion in the pig have similar
      pharmacology, possibly with slight differences in agonist potencies. In contrast
      to the guinea pig, porcine CCKB receptors appear to have no direct role in
      pepsinogen secretion.

PMID- 8875602
TI  - Role of protein kinase C in duodenal mucosal bicarbonate secretion in the guinea
      pig.
AB  - Since duodenal bicarbonate secretion (DBS) is increased by m-cholinoceptor
      agonists, it was postulated that protein kinase C (PKC) has a role in this
      secretion. This premise was examined in guinea pigs, using 12-O-tetradecanoyl
      phorbol 13-acetate (TPA) to stimulate bicarbonate production in the perfused
      duodenum in vivo, and to activate PKC in isolated duodenal enterocytes. TPA (10(
      7) mol.kg-1) infused intravenously stimulated active DBS from basal values of
      3.64 +/- 0.66 to 8.73 +/- 1.59 mumol.cm-1.10 min-1. This effect was completely
      blocked by verapamil (4 x 10(-7) mol.kg-1). PKC activity in duodenal enterocytes
      in the basal state was most abundant in the cytosolic fraction (2,221 +/- 444
      U/mg protein) and very low in the particulate fraction (227 +/- 51 U/mg protein).
      TPA (10(-7) mol.kg-1) caused a time-dependent translocation of the cytosolic,
      lipid-dependent activity of PKC into the particulate fraction. The effect was
      maximal at 5 min incubation and was reversed by 30 min. In the particulate
      fraction, this activity was no longer lipid-dependent, but could be stimulated by
      Ca2+ alone. These data support the hypothesis that translocation of PKC may
      contribute to DBS.

PMID- 8875603
TI  - Bladder dysfunction in the spontaneously diabetic male Abyssinian-Hartley guinea
      pig.
AB  - The spontaneously diabetic adult male Abyssinian-Hartley guinea pig develops
      bladder hypertrophy and voiding dysfunction. In contrast to animals with
      chemically induced diabetes, this animal demonstrates changes in bladder function
      in the absence of diuresis. The diabetic guinea pigs void a total daily volume
      similar to that of control animals, but have a greater mean volume per void and a
      longer interval between voiding. Cystometry demonstrates that the diabetic guinea
      pig produces greater intraluminal bladder pressure, but maintains voiding
      pressure for a shorter interval. A significantly decreased contractile response
      of the diabetic bladder base may be responsible for the bladder hypertrophy and
      voiding dysfunction.

PMID- 8875604
TI  - Hepatitis C and its sequelae: the biology of hepatitis C virus and implications
      for its control.
AB  - Hepatocellular carcinoma is one of the most important cancers worldwide and at
      least two hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV)
      appear to be etiologically associated with its development. Regardless of the
      nature of this association, control of these two viruses would likely be
      effective in the prevention of hepatocellular carcinoma. The control of HBV is
      achievable through proper utilization of highly effective vaccines against HBV.
      However, the development of useful vaccines against HCV will require more
      knowledge about the genetic and serologic heterogeneity of this virus and the
      nature of the host's immune response to it.

PMID- 8875605
TI  - HCV and liver cancer: the epidemiological evidence.
AB  - Hepatitis C virus (HCV) is a major cause of liver cancer in the developed areas
      of the world. It is estimated that over 100 million individuals are chronically
      infected with the virus worldwide and are at high risk of progression to liver
      disease and liver cancer. Exposure to contaminated blood and blood products,
      mother-to-child transmission, and exposure to infected household contacts are
      risk factors for infection. About half of the community-acquired infections are
      acquired by uncertain routes.

PMID- 8875606
TI  - Hepatitis C virus in chronic liver disease and hepatocellular carcinoma in
      Taiwan.
AB  - Hepatitis B virus (HBV) has long been known to be the major etiologic factor of
      chronic liver diseases and hepatocellular carcinoma (HCC), and in Taiwan 80-90%
      of chronic liver diseases and HCC are caused by HBV. Assays for antibody to
      hepatitis C virus (HCV) and to detect its viral genome (HCV-RNA) have revealed
      HCV as the next most common cause of these diseases in Taiwan. The prevalence of
      antibody to HCV (anti-HCV) in hepatitis B surface antigen (HBsAg)-negative
      patients is around 70-80%, and most of the patients are viremic. Anti-HCV is
      found in 0.5-1.0% of healthy adults. The epidemiology of HCV infection in Taiwan
      is similar to other areas of the world, with horizontal transmission as the major
      route of infection. Blood transfusion was an important route of transmission,
      accounting for 30-40% of chronic HCV infection. After screening for anti-HCV in
      blood donors was instituted, this infection route was effectively controlled. The
      nucleotide sequences of a Taiwanese isolate of HCV are similar to Japanese
      isolates (homology of > 90%) and less similar to the prototype U.S. isolate (78%
      homology). The predominant genotype is type II/lb, being detected in 66-71% of
      patients with chronic hepatitis C and in 83% of those with cirrhosis or HCC.
      Analysis of serum HCV cDNA levels by competitive polymerase chain reaction showed
      that the levels ranged from 10(1) to 10(7) copies/ml and did not correlate with
      the gender of the patients, past blood transfusion, serum aminotransferase
      activities, or histologic severity. However, the serum HCV levels were higher in
      patients with genotype II/lb than those with type III/2a or type IV/2b (p <
      0.005), indicating genotype as an important determinant of levels of HCV viremia.
      Mixed infections of multiple genotypes of HCV may contribute to the acute
      exacerbations of chronic hepatitis C; among 20 patients with exacerbations, 11
      (55%) had evidence indicating the emergence of a different predominant HCV
      genotype; among 26 without exacerbations, this was found in only 2 (8%) (p <
      0.005). The incidence of HCC was studied by prospective follow-up of patients
      with cirrhosis by regular hepatic ultrasound examinations and serum alpha
      fetoprotein surveillance in the following four groups: i) HBsAg-positive, 300
      patients; ii) anti-HCV positive, 151 patients; iii) both positive, 144 patients;
      and iv) both negative, 62 patients. Each year, 3-5% developed HCC, and the
      difference in incidence between the four groups was not statistically
      significant. The mean age when HCC was detected was 56 +/- 10, 63 +/- 9, 55 +/-
      11 and 60 +/- 14 years in each group, respectively. The results indicate a high
      incidence of HCC in cirrhotic patients in Taiwan, whether the cirrhosis was
      related to HBV or HCV; dual infections of both viruses did not accelerate the
      occurrence of HCC. Although most anti-HCV-positive patients with HCCs had
      cirrhosis, HCC did occur in some patients without cirrhosis. Studies of these two
      groups of HBsAg-negative, anti-HCV-positive HCC patients revealed less frequent
      detection of HCV-RNA in serum and lower titers of HCV RNA in HCC without
      cirrhosis. In fact, 10/20 (50%) non-cirrhotic HCC patients were actually positive
      for serum HBV DNA by PCR, indicating the possible role of HBV in the etiology of
      HCC in these patients.

PMID- 8875608
TI  - Association of hepatitis C virus and hepatocellular carcinoma in the United
      States.
AB  - Hepatocellular carcinoma (HCC) is a common cause of death from cancer on a
      worldwide basis. Chronic hepatitis B virus (HBV) infection is a well-documented
      pathogenic factor in the etiology of HCC, accounting for the majority of cases in
      certain geographic areas where HBV chronic-infection rates are high. Recent
      studies have implicated hepatitis C virus (HCV) infection as another major
      etiologic agent of hepatitis B surface antigen (HBsAg)-negative HCC. Studies in
      Europe have demonstrated that HCV infection is commonly associated with HCC; the
      prevalence rates of HCV ranged from 39% to 77% of HCC patients in these studies.
      In areas where HBV infection is endemic, such as Africa and Japan, the prevalence
      rates of anti-HCV in individuals with HCC have been reported at 29% and 68%,
      respectively. The significance of HCV and HBV infections in contributing to the
      occurrence of HBsAg-negative HCC has not been well established in the United
      States. The clinical consequences of infection with different genotypes of HCV
      (defined by nucleotide sequence divergence) are largely unknown: several studies
      have suggested differences among genotypes in terms of clinical expression,
      disease progression, and response to treatment with interferon. Our recent
      studies demonstrated that HCV and occult HBV infections account for the majority
      of cryptogenic HCC cases in the United States. Preliminary studies on the
      prevalence of HCV genotypes in patients with or without HCC but otherwise matched
      for hepatic histology did not reveal any association of specific genotype(s) with
      development of HCC.

PMID- 8875607
TI  - Hepatitis C virus infection in black patients with hepatocellular carcinoma in
      southern Africa.
AB  - Chronic hepatitis C virus (HCV) infection is implicated in the etiology and
      pathogenesis of a relatively small proportion of hepatocellular carcinomas (HCC)
      in black residents of southern Africa. The major risk factor for the tumor in
      this population is chronic hepatitis B virus (HBV) infection acquired early in
      life. Only 13.2% of black patients with HCC are currently infected with HCV (as
      judged by the presence of HCV RNA in serum) alone, and another 4.3% are infected
      with both HCV and HBV. Antibody to HCV can be detected with second generation
      assays in 19.5% of HCC patients. Fifty percent of the HCC patients have only
      current HBV infection and a further 35.9% show markers of past HBV infection
      (including 9.1% who also are currently infected with HCV). The prevalence of
      current HBV infection is significantly lower in HCV RNA-positive than in HCV RNA
      negative patients, and this difference is independent of the sex, age, or
      geographical location of the patients. Only 5.4% of HCC patients are not infected
      with either HBV or HCV. Patients with HCV-associated HCC are appreciably older
      than those with tumors not associated with HCV and those with tumors associated
      with HBV, and the differences are independent of geographical location of the
      patients. Patients with HCV-associated HCC are more likely to be urban dwellers
      and less likely to be rural dwellers than are those with HBV-related tumors.
      Differences in sex distribution and alpha-fetoprotein levels just fail to reach
      statistical significance between patients with HCV-related and HBV-related HCC.
      The pathogenesis of HCV-related HCC in black Africans, as in all populations, is
      uncertain. A direct carcinogenic effect appears unlikely, and the available
      evidence favors an indirect effect mediated via chronic necroinflammatory hepatic
      disease. Because very few of our patients undergo surgery or have a necropsy
      performed, the relationship between HCV-associated HCC and cirrhosis in black
      Africans has not been analyzed.

PMID- 8875609
TI  - Molecular and genetic epidemiology of hepatocellular carcinoma: studies in China
      and Senegal.
AB  - To identify environmental, viral, and genetic factors that may influence the risk
      of developing hepatocellular carcinoma (HCC), large prospective studies are being
      conducted in Haimen City, China and Senegal, and a case-control study of genetic
      variation in the detoxification of aflatoxin-B1 was carried out in Shanghai,
      China. Analysis of 78 HCCs that have occurred among 51,020 men enrolled in a
      large prospective study in Haimen City, China showed a strong association of HCC
      with chronic hepatitis B virus (HBV) infection. There were also significant
      associations of HCC risk with occupation (farming), history of a clinical episode
      of hepatitis in adulthood, and a family history of HCC. Study of 52 HCC cases and
      116 controls for genetic polymorphisms and HCC risk showed a significant
      association with epoxide hydrolase (EPHX) mutant alleles (1/2, 2/2) and a
      borderline association with homozygous deletion of the glutathione-S-transferase
      mu (GSTM1) gene. There was a multiplicative interaction of these polymorphisms
      with chronic HBV infection such that HBsAg-positive persons who were GSTM1 null
      and were EPHX 1/2 or 2/2 had 135 times the risk of HCC as HBsAg-negative persons
      with the wild type genotypes for GSTM1 and EPHX. The risk of HCC is not uniform
      among persons with chronic HBV or HCV infections. Studies of genetic, viral, and
      environmental interactions may permit identification of those individuals at
      highest risk within groups at increased risk of HCC. Prevention strategies could
      then be targeted at those individuals.

PMID- 8875610
TI  - Hepatocellular carcinoma and infections with multiple hepatitis viruses.
AB  - Hepatitis B virus (HBV) plays a major role in liver carcinogenesis. HBV-DNA
      integration into cellular DNA provides some molecular basis for understanding the
      mechanisms of neoplastic transformation of the liver cell. Persistence of HBV-DNA
      episomic forms, necro-inflammation in the liver, and cirrhosis appear to be
      additional promoting factors. We studied the possible association between
      hepatocellular carcinoma (HCC) and the defective hepatitis D virus (HDV), a virus
      that requires the helper function of HBV. Patients infected with HDV and HBV
      develop HCC about 10 years earlier than those infected with HBV alone.
      Persistence of active HDV disease and low levels of "wild-type" HBV (i.e.,
      secreting the hepatitis B surface antigen [HBsAg]) are associated with
      progressive liver disease and HCC. Therefore, HBV replication, in spite of being
      inhibited by HDV, appears to play a major role sustaining HDV pathogenicity.
      Detection of antibody to the hepatitis C virus (HCV) in many HCC patients raises
      the important question whether HCV has oncogenic potential. Clinico
      epidemiological data show that the most severe forms of liver disease in patients
      with multifactorial liver damage occur in those infected with HCV. The prevalence
      of HBV markers in patients with cirrhosis, HCC, and HCV infection is higher than
      in individuals with comparable age and other diseases. HBV-DNA integration
      occurring early during HBV infection can persist in those with and without
      detectable HBsAg in their serum. Therefore, one can speculate that in patients
      with integrated HBV-DNA and concurrent HCV infection, cirrhosis and HCC may
      develop more easily than in patients without HBV-DNA integration. HCV hampering
      the immune system also might play a role in the genesis of HCC. The evidence that
      multiple hepatitis viruses are more frequently associated with HCC than
      infections of one virus alone has important practical consequences. It warrants
      the identification of high risk patients so that they can be monitored frequently
      for early diagnosis and treatment.

PMID- 8875611
TI  - Clinical pathoepidemiology of hepatocellular carcinoma in Japan.
AB  - There has been a rapid increase in the number of patients with hepatocellular
      carcinoma (HCC) in Japan. This may be the result of an increased number of
      patients with hepatitis C virus (HCV)-related liver disease, and of prolonged
      survival of these patients due to improvement in the management of cirrhosis.
      Indeed, 96% of recent HCC patients admitted to our hospital were related to viral
      hepatitis B or C, and HCV infection accounted for three-fourths of these cases.
      Since most HCCs develop in the course of chronic liver disease, it is important
      to identify high risk groups for HCC development and to detect small HCCs early.
      We have established a screening method by combining various imaging studies and
      the measurement of serum alpha-fetoprotein; this combination has markedly
      increased the detection of small HCCs less than 2 cm in diameter. Multiple HCCs
      can occur in the same patient, either simultaneously or successively. Partly for
      this reason, the cumulative recurrence rate of HCC is very high even after
      surgical resection. In order to determine whether such HCCs arise from the common
      or different clonal origins, we have utilized the restriction landmark genomic
      scanning method. It remains to be clarified whether HCV plays a direct role in
      hepatocarcinogenesis, and whether antiviral treatments such as interferon
      eventually will decrease the incidence of HCC among patients with chronic HCV
      infection.

PMID- 8875612
TI  - Genetic heterogeneity of the hepatitis C virus.
AB  - Hepatitis C virus (HCV) is an important etiological agent in the development of
      chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular
      carcinoma (HCC). The virus, identified only recently, contains a single-stranded
      RNA genome of positive polarity, is distantly related to pestiviruses and
      flaviviruses, and has been classified as the first member of a third genus within
      the family Flaviviridae. Extensive analysis of HCV genomic sequences demonstrated
      that this virus possesses significant genetic heterogeneity. Different regions of
      the viral genome demonstrate a varying degree of heterogeneity; the regions
      coding for the putative envelope proteins are the most variable sites between
      different isolates. Furthermore, HCV circulates as a quasispecies in the host.
      During the course of acute and chronic infection, the sequence composition of the
      HCV population in one patient has been found to change sequentially with an
      extremely high rate of nonconserved nucleotide changes in the hypervariable
      region I (HVR1) of HCV. Such sequence changes alter the antigenicity of the
      epitopes coded within HVR1 so that these are not always recognized by preexisting
      antibodies. It has been suggested that this could represent one mechanism by
      which HCV evades host immune surveillance and may account for the high rate of
      chronicity observed in such infections. Continuous viral replication may, in
      turn, lead to the development of chronic liver disease, including HCC, in
      infected individuals. To date, at least nine major genetic groups (genotypes 1-9)
      and more than 30 subgroups of HCV have been recognized based on genetic
      differences. A distinct difference has been observed in the genotype distribution
      in Africa compared with other continents. Recent data have suggested a difference
      in pathogenesis and in the outcome of interferon therapy in individuals infected
      with HCV of certain genotypes. For example, genotype 1b (II) seems to be
      associated with more severe liver disease, including HCC, and with a poorer
      response to interferon therapy. The extensive genetic heterogeneity of HCV may
      have serious implications for the diagnosis, treatment and prevention of
      hepatitis C as well as in understanding the biology of infection by this
      important human pathogen.

PMID- 8875613
TI  - Characterization of hepatitis C virus core protein.

PMID- 8875614
TI  - Translation of hepatitis C virus genome.
AB  - Translation of the human hepatitis C virus (HCV) RNA genome occurs by internal
      ribosome entry through the 5' end (5' noncoding region) in a cap-independent
      fashion. The relatively long stretch of this noncoding region contains multiple
      initiation codons that are apparently not used for translation. Translation of
      the HCV polyprotein is initiated instead from an AUG located at nt 342. Using
      computer-assisted analysis (and subsequently substantiated by enzymatic probing),
      a complex secondary and tertiary structure of the 5' noncoding region (5'NCR) has
      been predicted. Based on an RNA folding model proposed by Brown et al. (1992), a
      detailed mutational analysis carried out identified the key secondary structural
      regions that are of functional significance in translational control. Maintenance
      of a helical structural element relevant to an oligopyrimidine tract is essential
      for internal initiation. A putative coaxial stacking or a pseudoknot structure
      upstream of the initiator AUG seems to be central to an internal ribosome entry
      site (IRES)-mediated translation of the HCV RNA genome.

PMID- 8875616
TI  - Processing of hepatitis C virus precursor polyprotein.
AB  - To elucidate the possible involvement of hepatitis C virus protein in the
      development of hepatocellular carcinoma. viral proteins produced from the largest
      open reading frame of the viral genome were analyzed. The function of each
      protein in virus replication was also examined. Virus proteins are produced by
      proteolytic cleavage by cellular and virus encoded proteinases. One of the viral
      proteins is a phosphoprotein, and the degree of phosphorylation is regulated by
      another viral protein. This regulation of phosphorylation may play an important
      role in modulating the proliferation of virus-infected cells.

PMID- 8875615
TI  - Mechanism of translation initiation on hepatitis C virus RNA.
AB  - In vitro translation experiments involving reticulocyte and HeLa cell lysates
      have demonstrated that translation initiation on hepatitis C virus (HCV) RNA
      occurs by entry of ribosomes to the internal sequence (internal ribosomal entry
      site [IRES]) within the 5' noncoding region (5'NCR). Specific binding factors
      that bind to the HCV IRES were examined by UV cross-linking tests. A protein p57
      (polypyrimidine tract binding protein [PTB]), known to be a binding factor that
      binds to picornavirus IRES, was found to bind to the HCV IRES. To investigate
      functions of this PTB in IRES-dependent translation initiation, hyperimmune
      antibodies to PTB (anti-PTB) were prepared by immunizing rabbits with purified
      recombinant PTB produced in E. coli. Anti-PTB IgGs were purified and used to
      deplete PTB in a cell-free protein synthesis system prepared from HeLa cells. In
      vitro translation experiments using PTB-depleted lysates suggested that host
      factor dependency of IRES is different in individual IRESs. As we showed
      previously, function of the IRES typical of group II HCV is more efficient than
      the IRES typical of group I HCV in a cell-free protein synthesis system from HeLa
      cells. Recombinant HCV IRESs were constructed and tested for their function in
      the in vitro system. Most recombinant IRESs showed an initiation activity of the
      more efficient typical group II IRES level or higher. This observation, together
      with the fact that group I HCV is the most common isolate of HCV worldwide,
      suggests that the efficiency of the IRES function of HCV may be generally
      suppressed in nature, and that the replication ability of HCV that permits its
      persistent infection in humans may require a delicate balance at a molecular
      level.

PMID- 8875617
TI  - Expression of HCV envelope proteins and the serological utility of the anti-E2
      immune response.
AB  - The 5' end of the hepatitis C virus (HCV) genome encodes structural proteins of
      the virion. The first gene encodes a highly basic core protein. Immediately
      downstream of the core gene are regions which encode the envelope proteins (E1
      and E2) of the virus. Artificial expression and secretion of immunologically
      active envelope proteins have proven to be a substantial challenge due to the
      high degree of glycosylation and the existence of certain hydrophobic domains
      contained within these sequences. Bacterial cell expression of recombinant HCV
      envelope proteins results in products that are not glycosylated and are poorly
      immunogenic. Emphasis has shifted to the use of mammalian cell lines (human
      embryonic kidney [HEK] and Chinese hamster ovary [CHO] cells) for the expression
      of glycosylated, immunologically active envelope proteins. Using HEK cells, E1 is
      expressed intracellularly but is not secreted from the cells. When E1 is cloned
      in fusion with a C-terminal truncated E2 protein, both proteins are detected
      intracellularly; however, only E2 is secreted. When the E1/E2 processing site is
      interrupted by constructing deletion mutants, the unprocessed E1/E2 fusion
      protein can be secreted from the cells. Quantifiable expression and secretion of
      a truncated E2 protein is now possible using CHO cells and SV40-based vectors.
      The HCV E2 glycoprotein expressed from CHO cells is highly antigenic; a strong
      humoral response to this antigen develops in persons infected with HCV.
      Antibodies to E2 are found in 95% of patients with detectable HCV RNA in their
      sera. The presence of antibodies to E2 is not indicative of viral clearance and
      therefore the role these antibodies play in protective immunity, if any, is
      unclear.

PMID- 8875618
TI  - Correlation of in vivo infectivity of hepatitis C virus to in vitro infectivity
      and to virion properties.
AB  - Serum from an individual who was chronically infected with hepatitis C virus
      (HCV) was inoculated into chimpanzees and a human T cell line. The serum
      contained a quasispecies population of HCV consisting of at least six genetic
      sequences. However, only two sequences (the same two sequences) were recovered
      both in chimpanzees and in cultured human T cell line, indicating that infection
      of the culture system reflects infection in vivo.

PMID- 8875620
TI  - Hepatocarcinogenesis: hepatitis viruses and altered tumor suppressor gene
      function.
AB  - Two different processes appear to be involved in the initiation of
      hepatocarcinogenesis by chronic hepatitis B virus (HBV) infection and by chronic
      hepatitis C virus (HCV) infection. Initiation of hepatocellular carcinoma (HCC)
      by chronic HBV infection usually occurs early in life; most patients have had
      onset of HBV infection before the end of childhood, although rare cases of HCC
      have been reported following HBV infections acquired in adulthood. In contrast,
      HCV-associated HCC in many cases probably develops after a chronic HCV infection
      that was acquired during adulthood. HBV-DNA usually is integrated in the tumor
      DNA of HBV-associated HCC; it produces two proteins that can transactivate known
      oncogenes in vitro and that theoretically could affect genes at distant sites in
      vivo. HCV is a nonintegrating virus and no transactivating HCV proteins have been
      identified so far. In the later stages of hepatocarcinogenesis, "tumor promotion"
      and "tumor progression," HBV-associated HCC may share certain features with those
      of HCV-associated HCC. Chronic inflammation and cirrhosis, accompanied by
      regenerative processes, may function as a tumor promoter, providing a common
      pathway from chronic HBV or HCV infection to HCC. Tumor progression may be
      brought about in HCC by mutations of the p53 tumor suppressor gene. Mutations of
      this gene are common in HCCs, and they are found more often in advanced human
      HCCs than in small, well-differentiated HCCs. The prevalences of p53 mutations
      are similar in HBV-associated and HCV-associated HCCs (30-50%). Even in the
      absence of a p53 mutation, the functions of normal p53 can be inactivated as a
      result of binding by viral or by cellular proteins. It is not known yet whether
      this type of binding contributes to the development of HCC, but p53 binding by
      the HBV X protein in vitro has been reported. Abnormalities of the RB tumor
      suppressor gene also have been found frequently in HCC patients, particularly in
      HCCs that contain p53 mutations.

PMID- 8875619
TI  - In vivo transfection of rat liver with hepatitis C virus cDNA using cationic
      liposome-mediated gene delivery.
AB  - The lack of a small animal model for hepatitis C virus (HCV) infection has
      impeded elucidation of the pathogenesis of this virus. The aim of this study was
      to develop an HCV-expressing animal model using cationic liposome-mediated in
      vivo gene transfer. To examine the feasibility of this strategy, an expression
      vector composed of the LacZ gene driven by the beta-actin promoter, pActLacZ, was
      injected retrogradely into the common bile ducts of adult rats. X-Gal
      histochemical staining clearly showed that the LacZ gene was expressed in
      hepatocytes. Maximal expression was observed at a DNA:lipofectin ratio of 1:4.
      Based on this observation, an expression vector containing the full-length of HCV
      cDNA, pAGS3M091, was evaluated in adult rats. Two days after intrabiliary
      administration of pAGS3M091, PCR amplification of reverse-transcribed liver RNA
      demonstrated the 5' and 3' portions of HCV transcripts derived from pAGS3M091.
      Immunohistochemical analysis revealed the HCV core protein in a small number of
      hepatocytes scattered in the lobules. Thus, the full-length of the HCV genome was
      successfully expressed in adult rat liver using liposome-mediated in vivo gene
      transfer.

PMID- 8875621
TI  - Target cell populations in virus-associated hepatocarcinogenesis.
AB  - Studies on the natural course of virus-associated hepatocellular carcinoma (HCC)
      in high risk areas, particularly hepatitis B virus (HBV), have shown a stage of
      persistent liver cell hyperplasia characterized by a low level elevation of serum
      alpha-fetoprotein (AFP). We have recently identified a population of epithelial
      cells with distinct structure and expression of cytokeratin and AFP in non
      neoplastic liver tissues from humans with HBV-associated HCC. These cells were
      characterized by oval nuclei, scant pale cytoplasm, small cell size, and cross
      reactivity to a monoclonal antibody against rat oval cells. These human
      epithelial cells, putative human oval-type cells, stained strongly positive for
      cytokeratin 19 and displayed considerable heterogeneity in AFP and albumin
      expression. These findings suggest that a cell population structurally and
      phenotypically similar to oval cells seen in the early stages of chemical
      hepatocarcinogenesis in the rat is also present in humans in regenerating liver
      lesions observed in HBV-associated HCC. Hepatitis B surface antigen (HBsAg) was
      detected in 69, 81, and 85% of oval-type cells, transitional cells, and
      hepatocytes, respectively, but not in bile ducts or ductular cells. Also, high
      levels of expression of transforming growth factor alpha (TGF-alpha) were
      frequently seen in oval-type and transitional cells expressing HBsAg. These data
      suggest the possibility that oval-type cells are a target cell population for HBV
      infection; in the presence of elevated TGF-alpha expression, these cells may
      constitute a progenitor population for human HCC.

PMID- 8875622
TI  - Preneoplastic lesions in chronic hepatitis C.
AB  - A significant proportion of patients with hepatocellular carcinoma (HCC) are
      infected with hepatitis C virus (HCV). This finding suggests that HCV infection
      is a major risk factor for the development of HCC. It is presently unclear
      whether HCV has a direct oncogenic effect on infected hepatocytes or whether
      continuous cell regeneration due to the chronic necroinflammatory process
      predisposes hepatocytes to mutations and malignant transformation. Except for
      rare cases, HCC in chronic HCV infection is always associated with cirrhosis. We
      examined a series of 138 consecutive cirrhotic livers with chronic hepatitis C
      that had been removed during transplantation for evidence of macroregenerative
      nodules (MRNs), liver cell dysplasia of large and small cell types, and HCC. MRNs
      and liver cell dysplasia are currently considered to be precursors of HCC. HCCs
      were present in 38 livers (28%) and were multifocal in half of the cases. MRNs
      were identified in 34 livers (25%). The number of MRNs ranged from 1 to 5 in 28
      patients and was greater than 5 in 6 patients. In 14 of 34 livers with MRNs,
      there were associated HCCs (41%). Eight MRNs contained microscopic HCC. No
      microscopic HCC was found outside of MRNs; however, grossly apparent HCCs might
      have arisen from MRNs. Large liver cell dysplasia (LLCD) was frequently observed.
      It was present in 97 livers (70%) with or without MRNs and/or HCCs. Small liver
      cell dysplasia (SLCD) was seen in 8 livers with MRNs and/or HCCs and in 1 liver
      without MRN and HCC. These findings suggest that in chronic HCV infection,
      multifocal HCC is often found. MRN may represent one pathway in
      hepatocarcinogenesis. LLCD, similar to that found in chronic hepatitis B virus
      (HBV) infection, is a common finding in HCV-infected livers with cirrhosis, and
      appears not to be directly related to the development of HCC. SLCD is rarely
      seen, but may represent an important step in malignant transformation.

PMID- 8875623
TI  - Pathomorphologic comparison of hepatitis C virus-related and hepatitis B virus
      related cirrhosis bearing hepatocellular carcinoma.
AB  - A morphologic comparison between hepatitis C virus-related cirrhosis (HCV
      cirrhosis) and hepatitis B virus-related cirrhosis (HBV cirrhosis) was performed.
      The materials consisted of 37 surgical specimens obtained from patients with
      hepatocellular carcinoma (HCC) positive for antibodies to HCV (anti-HCV) and
      negative for HBV serologic markers, and 21 specimens from patients positive only
      for hepatitis B surface antigen (HBsAg). In addition, the evolution of the type
      of cirrhosis associated with HCC was studied in 43 autopsy cases from 1970 to
      1975 and 44 cases from 1989 to 1994. The histological features of HCV cirrhosis
      are characterized by broadly expanded fibrous septa, small regenerative nodules,
      and a relatively strong inflammatory reaction with prominent lymphoid aggregation
      and mild regenerative activity of the hepatocytes. HBV cirrhosis is characterized
      by larger regenerative nodules, a weak inflammatory reaction, and marked
      regenerative activity of the hepatocytes. In a comparison of the types of
      cirrhosis associated with HCC during the six-year period from 1970 to 1975 with
      the six-year period from 1989 to 1994 at Kurume University School of Medicine,
      macronodular cirrhosis (which was mostly HBsAg-positive) declined from 38.8% to
      13.6%; by 1989-1994, most of the associated cirrhosis was mixed macronodular and
      micronodular type with anti-HCV in serum (in 84%). The morphologic type of
      cirrhosis associated with HCC reflected the proportion of viral hepatitis due to
      HBV or HCV involved.

PMID- 8875624
TI  - Viral co-factors in liver cancer: lessons from hepatitis B virus.
AB  - Hepatitis B virus (HBV) is a co-factor in some hepatocellular carcinomas (HCC).
      Chronic infection with HBV is a risk factor for tumor development, suggesting the
      accumulation of cellular genetic changes. HBV DNA is frequently found integrated
      at random sites in HCC, with chromosomal deletions and rearrangements being
      common at the sites of viral integration. Tumor suppressor gene p53 is frequently
      altered in HCC. Environmental carcinogens are factors in HCC development in
      certain geographic locations. HBV encodes a protein (X) known to transactivate
      viral and cellular genes; the X gene is often retained in HCC. To learn more
      about X gene function. We employed the yeast two-hybrid genetic system to seek X
      interactive proteins. A cellular protein, designated XAP-1, was recovered that
      interacts specifically with the X protein. XAP-1 is the human homologue of the
      monkey UV-damaged DNA-binding protein (UV-DDB); the UV-DDB protein functions in
      DNA repair and is defective in some xeroderma pigmentosum group E patients. The
      interaction between XAP-1 and HBV X protein was confirmed by several independent
      methods. This suggests that cellular DNA repair processes may be affected by HBV
      and that the resulting genetic instability may contribute to hepatocellular
      carcinogenesis. A unifying model of the molecular basis of HBV involvement in HCC
      development is presented. Fundamental components of the model are chronic
      infection by HBV and viral effects on cellular DNA repair. This model has
      implications for the possible role of HCV infection in the induction of HCV
      associated HCC.

PMID- 8875625
TI  - Hepatitis B and C viruses in hepatitis B surface antigen negative hepatocellular
      carcinoma patients.
AB  - Hepatitis B virus (HBV) has been recognized for a long time as a major
      etiological factor in hepatocellular carcinoma (HCC) in endemic regions. HCCs
      occurring in Europe, an area with a low prevalence of HBV infections, are in fact
      also linked to chronic HBV infection, as revealed by the detection of the viral
      genome and HBV X gene transcripts in the tumor. There is also a significant
      association with hepatitis C virus (HCV) infection and a complex interplay may
      occur between HBV, HCV, and other environmental factors such as alcohol, as well
      as genetic factors. Preliminary evidence exists for a role of HCV in liver
      carcinogenesis even without the pre-existing cirrhosis.

PMID- 8875626
TI  - Structure and selection of hepatitis B virus variants during the natural course
      of infection and interferon therapy.
AB  - The consequences of hepatitis B virus (HBV) infection range from asymptomatic
      transient and chronic infections to mild and severe forms of hepatitis up to the
      development of liver cirrhosis and hepatocellular carcinoma. Immune-mediated
      destruction of infected liver cells plays a major role in HBV pathogenesis.
      Escape from immune-recognition by changing the antigenic make-up of HBV or by
      preventing the expression of some viral proteins leads to the emergence of viral
      variants. Variants can harbor mutations in the pre-core/core gene (pre C/C) or
      the preS/S gene, either of which can play a role in immune escape, viral
      persistence, and pathogenesis. A novel method has been developed to facilitate
      identification and functional analysis of full-length variant genomes of HBV,
      with implications for HBV diagnosis and therapy.

PMID- 8875627
TI  - Cytotoxic T lymphocyte responses in hepatitis C virus infection.
AB  - To clarify whether abnormal cytotoxic T lymphocyte (CTL) responses to hepatitis C
      virus (HCV) contribute to viral persistence and the development of subsequent
      chronic liver disease, we studied CTL responses of peripheral blood lymphocytes
      (PBLs) to HCV in patients with human leukocyte antigen (HLA) B44. CTLs were
      generated from PBLs by repeated stimulation with a synthetic HCV nucleoprotein
      peptide. The recognition of the peptide by CTLs was not strong and was restricted
      by an HLA B44 molecule. The minimal optimal epitope was a 9-mer peptide of HCV
      nucleoprotein residues 88 to 96. The CTLs also recognized an HCV antigen produced
      by a recombinant vaccinia virus construct. The CTLs could be induced from PBLs in
      4 of 9 patients with past or ongoing HCV infection. Two of the 4 patients who
      demonstrated the CTL responses had cleared HCV from the circulation. In one of
      the 4 patients, the infecting strain of HCV was a mutant: this patient's CTLs
      recognized the variant peptide less efficiently than the wild-type peptide. In
      the remaining one patient, the amino acid sequence of serum HCV nucleoprotein
      residues 88 to 96 was that of a wild-type HCV but the titer of HCV RNA in serum
      was low. All 5 patients who did not demonstrate the CTL responses had high titers
      of a wild-type HCV in their serum. Thus, insufficient CTL responses to HCV and
      emergence of HCV variants that escape recognition by CTLs or otherwise prevent
      the CTL response may contribute to HCV persistence resulting in the subsequent
      development of chronic liver disease.

PMID- 8875628
TI  - Association of cytotoxic T lymphocyte (CTL) escape mutations with persistent
      hepatitis C virus (HCV) infection.
AB  - Mechanisms by which HCV evades the cellular immune response in persistently
      infected humans and chimpanzees are poorly defined, but could involve mutations
      in epitopes recognized by class I MHC restricted CTLs. To investigate this
      possibility, we identified an epitope in the NS3 protein of HCV that was
      recognized by intrahepatic CTLs from a chimpanzee that developed persistent HCV
      infection after experimental challenge with the virus. Fine mapping studies with
      truncated synthetic peptides revealed that the epitope was 9 amino acids in
      length, encompassing residues 1445 to 1454 (GDFDSVIDC) of NS3. This sequence was
      completely conserved in all full-length NS3 genomes described to date. In view of
      the fact that the major genotypes of HCV may differ by up to -30% in overall
      amino acid homology, it appears in contrast that this epitope is highly
      conserved. The role of CTL escape mutations in HCV persistence was assessed in
      the virus inoculum used to infect this chimpanzee and in post-inoculation plasma
      samples. Sequencing of 6-10 M13 clones containing a 232-nucleotide fragment
      amplified with NS3-specific primers revealed that the epitope in the challenge
      inoculum and a post-inoculum plasma sample obtained at week 4 were identical to
      the published sequence of HCV-I. In contrast, all molecular clones sequenced from
      week 16, 25 and 28 plasma samples contained a single Asp--> Glu (D-->E) amino
      acid substitution at residue 1449. Significantly, four independently derived CTL
      clones established from the liver of this chimpanzee at various times up to two
      years after infection recognized target cells pulsed with a nonameric peptide
      representing the wild-type HCV-I sequence, but not those pulsed with a peptide
      containing the D-->E mutation. These data suggest that CTL escape mutations may
      play a role in viral persistence.

PMID- 8875629
TI  - Prospects for prophylactic and therapeutic hepatitis C virus vaccines.

PMID- 8875630
TI  - The present status of treatments for hepatocellular carcinoma.
AB  - In Japan, hepatocellular carcinoma (HCC) has developed almost exclusively in
      patients with chronic liver diseases associated with hepatitis B virus (HBV) or
      hepatitis C virus (HCV). Small HCCs have been found in considerable numbers when
      following up such patients. Percutaneous ethanol injection therapy (PEIT) has
      become an important therapy for small HCCs, with a 5-year survival rate of > 50%,
      similar to that of surgical resection. Such patients must be followed every 3
      months even after the initial successful treatment in order to detect newly
      developed lesions. For nodular HCCs, transcatheter chemoembolization (TAE) is the
      treatment of choice for advanced disease, but it is not a curative treatment; it
      can be given with PEIT with better results. Very advanced HCCs are usually
      treated with intra-arterial chemotherapy and the prognosis has been improved by
      using an implantable injection port system. The search continues for a means to
      prevent the recurrence of HCC after successful treatment.

PMID- 8875631
TI  - Treatment of unresectable hepatocellular carcinoma: targeted therapies using
      iodized oil.
AB  - Arterially administered iodized oil (Lipiodol) localizes selectively in HCCs for
      prolonged periods. Lipiodol-based intra-arterial chemotherapy and
      chemoembolization have yielded tumor response rates and survival benefits better
      than those offered by other therapies for unresectable Okuda Stage I and II HCC.
      Further trials are indicated to compare the different Lipiodol-cytotoxic-embolic
      regimens available. Early results of Lipiodol-targeted radiotherapy are
      available. This is a promising therapeutic development, and warrants comparison
      with chemoembolization in a large prospective randomized trial.

PMID- 8875632
TI  - Surgical treatment of hepatocellular carcinoma.

PMID- 8875633
TI  - Survival after liver transplantation in patients with hepatocellular carcinoma.
AB  - During a 12-year period (1981-1992), 3,029 patients, including 220 with
      hepatocellular carcinoma (HCC), received their first orthotopic liver
      transplantation (OLTX) for various liver diseases. One-, three- and five-year
      survivals of these 220 patients with HCC were 68%, 46%, and 37%, respectively,
      and those of the 2,809 patients without HCC were 78%, 71%, and 67.0%,
      respectively. Among the 220 patients with HCC, the following factors were
      associated with a poor prognosis: multiple tumors, HCC in two lobes of the liver
      ("bilobar tumors"), micro- and macroscopic vascular invasion, lymph node
      metastasis, tumor within the surgical margin, Stage IV HCC, and male gender.
      Cirrhosis and detection of hepatitis B surface antigen (HBsAg) or antibody to
      hepatitis C virus (anti-HCV) did not influence the survival rates after OLTX in
      the presence of HCC. By multivariate analysis, the negative prognostic value of
      only vascular invasion, bilobar distribution, and lymph node metastasis reached
      significance. As vascular invasion of HCC was the most significant prognostic
      factor after OLTX, its incidence was examined according to the following three
      radiologic measurements of the HCC before operation: (1) size, (2) lobar
      distribution, and (3) number of HCC nodules. Fifty percent of the HCCs of greater
      than 5 cm diameter had macroscopic vascular invasion, and 1-, 3- and 5-year
      survivals of the patients with these HCCs were 60%, 30%, and 18%, respectively,
      after OLTX. Nearly 50% of the bilobar HCCs also had macroscopic vascular
      invasion, and 1-, 3- and 5-year survivals were 56%, 29%, and 15%, respectively,
      after OLTX. One-third of multiple tumors had macroscopic vascular invasion, and 1
      , 3- and 5-year survivals were 64%, 38%, and 27%, respectively. However, survival
      after OLTX in patients with bilobar HCCs of < or = 2 cm diameter (even when these
      were Stage IV) was as good as in patients without HCC who had OLTX. The 5-year
      survival rate of the patients with unilobar, multiple HCCs without macroscopic
      vascular invasion, lymph node invasion and distant metastasis was 60%. These data
      indicate that HCCs of up to 5 cm diameter without macroscopic vascular invasion
      and nodal or distant metastasis can be effectively treated by OLTX.

PMID- 8875634
TI  - Urinary excretion of 2,3-dinor-6-keto-PGF1 alpha and 11-dehydro-TXB2 by the
      gravid spontaneously hypertensive rat.
AB  - Little is known about the pathophysiological processes leading to superimposed
      preeclampsia. We present an animal model where the uteroplacental blood flow in
      spontaneously hypertensive rats (SHR) was reduced by a silver clip. Thus, a
      superimposed preeclampsia-like syndrome could be studied under defined
      conditions. Urinary excretion of 2,3-dinor-6-keto PGF1 alpha and 11-dehydro-TxB2
      were measured by enzyme immunoassays at day 16 and 20 of pregnancy. In gravid,
      sham-operated animals excretion of 2,3-dinor-6-keto-PGF1 alpha was largely
      elevated compared to non gravid control animals (day 16: 1259 vs. 258 ng/kg 24h;
      day 20: 471 vs. 269 ng/kg.24h). However, in the gravid rats with reduced
      uteroplacental blood flow urinary excretion of 2,3-dinor-6-keto-PGF1 alpha
      decreased to non gravid levels (day 16: 335 ng/kg.24h; day 20: 238 ng/kg.24h). By
      antihypertensive therapy with dihydralazin this effect was largely abolished.
      Only minor alterations were found in the excretion of 11-dehydro-TxB2. Our
      findings suggest, that a reduction of uteroplacental blood flow in the
      spontaneously hypertensive rat decreases the systemic prostacyclin synthesis.

PMID- 8875635
TI  - Differential expression of cyclooxygenase-1 and -2 proteins in rat uterus and
      cervix during the estrous cycle, pregnancy, labor and in myometrial cells.
AB  - The synthesis of prostaglandins in the uterus at term are modulated by two
      isoforms of the enzyme cyclooxygenase (COX): constitutive COX-1 and inducible COX
      2. This study aims to characterize the expression of the protein for COX-1 and -2
      in the rat uterus and cervix during the estrous cycle, pregnancy, and labor, and
      in cultured myometrial cells. Western immunoblotting of proteins was performed
      and quantitation of protein was obtained densitometrically. Results indicate: 1)
      the rat uteri, cervix, and isolated myometrial cells express both COX-1 and COX-2
      proteins, 2) during pregnancy, both COX-1 and -2 increase, with a dramatic
      increase at parturition (250%-280%), 3) a 2-fold increase of cervical COX-2 is
      seen at spontaneous labor, 4) during proestrus and estrus, uterine expression of
      COX-2 is elevated, 5) both COX-1 and -2 were expressed by rat myometrial cells
      and treatment with IL-1 beta (10 ng/mL) produced a significant increase in COX-2,
      and 6) immunocytochemical studies show that both COX-1 and -2 were primarily
      localized to the epithelial cells of the endometrium and smooth muscle cells in
      the circular layers of the myometrium in the uterus and to the epithelial cells
      and smooth muscle cells in the cervix. Thus, we propose that increased expression
      of COX-2 may be involved at term in increased uterine contractility and cervical
      ripening.

PMID- 8875636
TI  - Multiplicity of rat liver 15-ketoprostaglandin delta 13-reductases.
AB  - Five kinds of 15-keto-PG delta 13-reductases (enzymes I, II, III, IV and V) were
      separated and purified from rat liver cytosol. Four (enzymes I,II, III and IV)
      out of these enzymes were homogeneous by the criterion of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The molecular weights of enzymes I, II, III
      and IV were estimated to be 40,000, 25,000, 64,000 and 70,000 by the
      electrophoresis, and 42,000, 23,000, 66,000 and 72,000 by gel filtration on a
      Sephadex G-200 column, respectively. All of these enzymes exhibited the NADPH
      dependent activities. In the cases of enzymes I, III and V, NADH was also
      effective as an electron donor, but to a lesser extent in enzymes I and III. The
      apparent K(m) values of enzymes I, II, III, IV and V for 15-keto-PGF2 alpha with
      NADPH were 276, 875, 842, 948 and 2767 nM. The enzymes had isoelectric points at
      4.5, 4.9, 6.2, 6.4 and 5.4, respectively. Enzyme I exhibited the double bond
      reductase activities toward alpha, beta-ketoalkenes such as trans-benzylidene
      acetone and trans-phenyl-1-propenylketone. Enzymes III and IV also catalyzed the
      double bond reduction of trans-phenyl-1-propenyl-ketone. All of these enzymes
      were markedly inhibited by various chemicals such as dicumarol, quercitrin, p
      chloromercuri-benzoic acid, 5,5'-dithio-bis(2-nitrobenzoic acid) and so on.

PMID- 8875637
TI  - Cyclosporin A inhibits prostaglandin E2 production by fetal amnion cells in
      response to various stimuli.
AB  - Use of cyclosporin A as part of an immunosuppressive regimen in pregnant
      transplant patients is not uncommon. Although successful pregnancies have been
      reported with the use of various immunosuppressive agents including cyclosporin
      A, the concern for fetal outcome still remains. Our purpose was to evaluate the
      effects of immunosuppressive cyclosporin A on prostaglandin E2 (PGE2) production
      by human fetal amnion. Amnion cells were isolated from term placentae obtained at
      elective cesarean section before the onset of labor. Cells were grown to
      confluence and then incubated for 16 hours with cyclosporin A (1-1000 ng/ml) in
      the presence and absence of interleukin 1 beta (IL-1 beta, 1 ng/ml), phorbol 12
      myristate 13-acetate (PMA, 10(-7) M) and ionomycin (0.5 microM). PGE2 was
      measured by radioimmunoassay and cellular protein determined. IL-1 beta, PMA and
      ionomycin all stimulated amnion cell PGE2 production as expected. However, these
      stimulatory actions were attenuated by at least 50% when cells were co-incubated
      with cyclosporin A (1000 ng/ml). Concentrations of cyclosporin A tested included
      the therapeutic range (250-1000 ng/ml). Our results indicate that cyclosporin A
      does not stimulate amnion cell PGE2 production and is probably unrelated to
      preterm labor and delivery in allograft recipients.

PMID- 8875638
TI  - Cytoprotective activity of cisapride on experimental gastric mucosal lesions
      induced by ethanol. Role of endogenous prostaglandins.
AB  - The antiulcer effects and protective mechanisms of cisapride, a prokinetic
      benzamide agonist of 5-HT3 and antagonist of 5-HT4 receptors, were investigated
      in gastric mucosal injury induced by pretreatment with 50% v/v ethanol in rats.
      The duration of the protective effect was also studied and the results were
      compared with those of 5-HT. 240 min after administration of cisapride (10, 25
      and 50 mg/kg) the total area of gastric lesions decreased significantly, in
      macroscopical and histological evaluations, and the mucus, hexosamine, and
      sulphated glycoprotein content were significantly increased. Indomethacin
      partially reversed cisapride protection suggesting that the beneficial antiulcer
      effects of this drug could be mediated in part by prostaglandins. This study
      confirms that this benzamide, in this experimental model, enhances gastric PGE2
      production. We also investigated the time course of action of 5-HT, 30-240 min
      before ethanol administration, and our study not only demonstrates the
      ulcerogenic action of the amine (30 min of pretreatment) but also its protective
      nature, shown macroscopic and microscopically, after 240 min of its
      administration, without any effect on PGs production. These findings suggest a
      new gastroprotective feature of cisapride partly explained through a
      prostaglandin-dependent mechanism and possibly independent of its 5-HT activity.

PMID- 8875639
TI  - Enzyme thermostability and thermoactivity.

PMID- 8875640
TI  - The subunit structure of human macrophage migration inhibitory factor: evidence
      for a trimer.
AB  - The subunit structure of human macrophage migration inhibitory factor (MIF) has
      been studied by preliminary X-ray analysis of wild-type and selenomethionine-MIF
      and dynamic light scattering. Crystal form I of MIF belongs to space group
      P2(1)2(1)2(1) and is grown from 2 M ammonium sulfate at pH 8.5. A native data set
      has been collected to 2.4 A resolution. Self-rotation studies and Van values
      indicate that three molecules per asymmetric unit are present. A data set to 2.8
      A resolution has been collected for crystal form II, which belongs to space group
      P3(1)21 or P3(2)21 and grows from 2 M ammonium sulfate, 2% polyethylene glycol
      (average molecular mass 400) 0.1 M HEPES, pH 7.5. Three, four, five or six
      monomers in the asymmetric unit are consistent with Van values for this crystal
      form. Analysis of crystal form II containing selenomethionine-MIF indicates nine
      selenium sites are present per asymmetric unit. Dynamic light scattering of MIF
      suggests that the major form of the protein in solution is a trimer. The results
      of these studies are in contrast to previous reports indicating that MIF is a
      monomer or dimer. The subunit arrangement of MIF is similar to that of tumor
      necrosis factor and suggests that signal transduction might require trimerization
      of receptor subunits.

PMID- 8875641
TI  - Evaluation of atomic level mean force potentials via inverse folding and inverse
      refinement of protein structures: atomic burial position and pairwise non-bonded
      interactions.
AB  - Two atomic level knowledge-based mean force interaction potentials (KBPs), a
      centrosymmetric burial position term and a long-range pairwise term, were
      developed. These were tested by comparing multiple configurations of three
      structurally unrelated proteins and were found successfully to (i) discriminate
      native state proteins from grossly misfolded structures in inverse folding tests,
      (ii) rank identify, using the KBP energy/r.m.s.d. correlation, native from
      progressively less native-like (compact and dilated) structures generated via
      molecular dynamics sampling, providing an energy gradient sloping from partially
      unfolded structures towards near-native states in inverse refinement tests (iii)
      smooth the overall potential energy surface in the region of dilated non-native
      structures by countering local minima of the in vacuo molecular mechanical
      potential and (iv) serve as a local minimum detector during simulated temperature
      quenching studies. These atomic KBPs discriminated native from non-native
      structures with greater overall sensitivity than did either a residue-based
      pairwise interaction potential or an effective solvation potential based on
      atomic contact volume occupancy. The KBPs presented here are immediately useful
      as a tool for selecting "good refinement candidates' from an arbitrary collection
      of protein configurations and may play a role in dynamic computational protein
      refinement.

PMID- 8875642
TI  - Predicting leucine zipper structures from sequence.
AB  - The leucine zipper structure is adopted by one family of the coiled coil
      proteins. Leucine zippers have a characteristic leucine repeat: Leu-X6-Leu-X6-Leu
      X6-Liu (where X may be any residue). However, many sequences have the leucine
      repeat, but do not adopt the leucine zipper structure (we shall refer to these as
      non-zippers). We have found and analyzed residue pair patterns that allow one to
      identify correctly 90% of leucine zippers and 97% of non-zippers. Simpler
      analyses, based on the frequency of occurrence of residues at certain positions,
      specify, at most, 65% of zippers and 80-90% of non-zippers. Both short and long
      patterns contribute to the successful discrimination of leucine zippers from non
      zippers. A number of these patterns involve hydrophobic residues that would be
      placed on the solvent-exposed surface of the helix, were the sequence to adopt a
      leucine zipper structure. Thus, an analysis of protein sequences has allowed us
      to improve discrimination between leucine zippers and non-zippers, and has
      provided some further insight into the physical factors influencing the leucine
      zipper structure.

PMID- 8875643
TI  - Relationship between thermal stability and 3-D structure in a homology model of 3
      isopropylmalate dehydrogenase from Escherichia coli.
AB  - To reveal the structural basis of the increased thermal stability of 3
      isopropylmalate dehydrogenase (IPMDH) from Thermus thermophilus, an extreme
      thermophile, the homology-based structural model of one mesophilic (Escherichia
      coli) counterpart, was constructed. Both IPMDHs are homodimeric proteins. We
      built a model of one subunit using the 3-D structures of the Th. thermophilus
      IPMDH and the homologous E.coli isocitrate dehydrogenase. Energy minimization and
      molecular dynamics simulated annealing were performed on the dimer, including a
      surrounding solvation shell. No serious errors were detected in the refined model
      using the 3-D profile method. The resulting structure was scrutinized and
      compared with the structure of the Th.thermophilus IPMDH. Significant differences
      were found in the non-specific interactions including the hydrophobic effect. The
      model predicts a higher number of ion pairs in the Th.thermophilus than in the
      E.coli enzyme. An increase was observed in the stabilities of alpha-helical
      regions in the thermophilic protein. The preliminary X-ray coordinates of the
      E.coli IPMDH were received after the completion of this work, allowing an
      assessment of the model in terms of the X-ray structure. The comparison proved
      that most of the structural features underlying the stability differences between
      the two enzymes were predicted correctly.

PMID- 8875644
TI  - Normal-mode analysis suggests important flexibility between the two N-terminal
      domains of CD4 and supports the hypothesis of a conformational change in CD4 upon
      HIV binding.
AB  - Human CD4 is the receptor for human immunodeficiency virus (HIV). It is well
      established that the first domain of CD4 binds with high affinity to gp120, an
      envelope protein of HIV, but it has also been demonstrated that amino acids
      located in its second domain, within or close to residues 120-127 or 163-166
      (lying 15 A away from the binding site), play a role in virus infectivity. We
      show here that these two stretches of amino acids happen to be important for the
      largest amplitude motion obtained with the normal-mode theory for the two N
      terminal domains of human CD4: an overall rigid-body displacement of one domain
      with respect to the other. Such a 'hinge-bending' motion is unexpected since
      these two domains were found by crystallographers to be tightly abutting. On the
      other hand, since for several proteins the hinge-bending motion experimentally
      observed upon ligand binding was found to be similar to the largest amplitude
      motion obtained with the normal-mode theory for these proteins, our results
      suggest that CD4 may undergo such a kind of conformational change upon HIV
      binding.

PMID- 8875645
TI  - Molecular mechanics calculations on HIV-1 protease with peptide substrates
      correlate with experimental data.
AB  - Molecular models of HIV-1 protease and 21 peptide substrates with single amino
      acid substitutions at positions from P4 to P3' were built and compared with
      kinetic measurements. The crystal structure of HIV-1 protease with a peptidic
      inhibitor was modified to model the peptide substrate Pro-Ala-Val-Ser-Leu-Ala-Met
      Thr for the starting geometry. Models were built of two reaction intermediates,
      HIV protease with peptide substrate and with its tetrahedral intermediate. The
      energy minimization used a new algorithm that increased the speed and eliminated
      a cut-off for non-bonded interactions. After minimization the models for
      substrate and tetrahedral intermediate both had root mean square deviations of
      0.48 A for all atoms of the HIV protease compared to the starting crystal
      structure. Differences in the model structures and interaction energies for HIV
      protease with different substrates were analyzed. The calculated interaction
      energies for the 21 HIV protease-tetrahedral intermediate models gave a
      correlation coefficient of 0.64 with the kinetic measurements. The eight
      substrates with changes in the P1 and P1' residues next to the scissile bond gave
      the highest correlation of 0.93, while the 14 substrates with changes in P2-P2'
      gave a correlation coefficient of 0.86. The catalytic mechanism and factors
      influencing the catalytic efficiency of the different substrates are discussed in
      relation to the models. The predictive ability of molecular mechanics
      calculations is discussed in the context of the statistical mechanics analysis of
      the differences in free energy.

PMID- 8875646
TI  - The active site of Trichoderma reesei cellobiohydrolase II: the role of tyrosine
      169.
AB  - Trichoderma reesei cellobiohydrolase II (CBHII) is an exoglucanase cleaving
      primarily cellobiose units from the non-reducing end of cellulose chains. The
      beta-1,4 glycosidic bond is cleaved by acid catalysis with an aspartic acid,
      D221, as the likely proton donor, and another aspartate, D175, probably ensuring
      its protonation and stabilizing charged reaction intermediates. The catalytic
      base has not yet been identified experimentally. The refined crystal structure of
      CBHII also shows a tyrosine residue, Y169, located close enough to the scissile
      bond to be involved in catalysis. The role of this residue has been studied by
      introducing a mutation Y169F, and analysing the kinetic and binding behavior of
      the mutated CBHII. The crystal structure of the mutated enzyme was determined to
      2.0 A resolution showing no changes when compared with the structure of native
      CBHII. However, the association constants of the mutant enzyme for cellobiose and
      cellotriose are increased threefold and for 4-methylumbelliferyl cellobioside
      over 50-fold. The catalytic constants towards cellotriose and cellotetraose are
      four times lower for the mutant. These data suggest that Y169, on interacting
      with a glucose ring entering the second subsite in a narrow tunnel, helps to
      distort the glucose ring into a more reactive conformation. In addition, a change
      in the pH activity profile was observed. This indicates that Y169 may have a
      second role in the catalysis, namely to affect the protonation state of the
      active site carboxylates, D175 and D221.

PMID- 8875647
TI  - Activation of E350A mutant maltodextrin phosphorylase by exogenously added
      acetate.
AB  - Site-directed mutagenesis of E350 to alanine in Escherichia coli maltodextrin
      phosphorylase reduced both enzyme activity (100-fold) and apparent binding of the
      oligosaccharide substrate (10-fold), suggesting a participation of this residue
      in binding of the substrate in the ground and transition states. The E350A mutant
      enzyme was found to be activated up to 20-fold by exogenous acetate ions which
      substitute for the deleted side chain. In contrast, apparent binding was not
      affected by acetate ions, indicating a dual role for the carboxylic group of this
      residue in catalysis and binding. Formate also appears to activate the E350A
      mutant enzyme, but this effect is obscured by the strong inhibitory effect of
      formate on the wild-type enzyme. For propionate ions, a weak 2-fold activation
      was noticed, while other compounds like trifluoroacetate and acetamide had no
      effects on the catalytic properties of either the E350A mutant enzyme or wild
      type enzyme. If E350 was substituted by a glutamine, no activation was observed
      upon the addition of acetate ions. However, a weak activation by formate was
      found, confirming that activation by acetate is caused by specific binding at the
      mutated site.

PMID- 8875648
TI  - Recombinant C-terminal domain of pancreatic lipase retains full ability to bind
      colipase.
AB  - The organization of the pancreatic lipase in two well defined domains has been
      correlated to a specific function for each domain, catalytic activity for the N
      terminal domain and colipase binding for the C-terminal domain. In order to see
      if such an organization implies that the two domains can behave as separate
      entities, we expressed the N- and C-terminal domains in insect cells. The
      recombinant proteins secreted in the cell supernatants present the expected
      molecular properties. However, whereas the C-terminal domain retains its function
      of colipase binding, the N-terminal domain appears to be unable to ensure
      catalysis. The lack of activity of the recombinant N-terminal domain could result
      either from a (partially) incorrect folding or from an incapacity to function by
      itself. These results suggest that, although both are structurally well defined,
      the two domains of the pancreatic lipase behave differently when they are
      expressed as separate entities.

PMID- 8875649
TI  - Expression of recombinant alpha Ains-crystallin and not alpha A-crystallin
      inhibits bacterial growth.
AB  - alpha A-Crystallin and alpha Ains-crystallin are derived from the alpha A
      crystallin gene via alternative splicing. They are identical except for the
      presence of a polypeptide, 23 amino acids long, encoded by the 'insert' exon.
      Evolutionary logic would suggest that the insertion of a 23 amino acid peptide in
      the middle of alpha A-crystallin, a protein evolving more slowly than either
      histone H1, cytochrome c or hemoglobin, would lead to appreciable structural and
      functional changes. However, based on physico-chemical studies, it is presently
      believed that alpha A-crystallin and alpha Ains-crystallin are functionally
      equivalent and that the presence of the 'insert' peptide in alpha Ains-crystallin
      is inconsequential. We report here that the independent expression of recombinant
      alpha Ains-crystallin, and not alpha A-crystallin, inhibits growth of the
      bacterial host. These observations were confirmed in coexpression experiments,
      wherein both the proteins were expressed in the same cell. Interestingly, growth
      inhibition is reversible. Importantly, the data demonstrate that it is catalytic
      amounts and not the gross accumulation of alpha Ains-crystallin which causes
      growth inhibition. Given the prior knowledge that alpha A-crystallin and alpha
      Ains-crystallin differ by a peptide of 23 amino acids, these data suggest that
      the "insert peptide' in alpha Ains-crystallin imparts properties on this protein
      that are different from alpha A-crystallin.

PMID- 8875650
TI  - How much care? Or is that the real question?

PMID- 8875652
TI  - Managed care: IV. Some helpful resources.

PMID- 8875651
TI  - Closing the gap between alcoholism research and practice: the case for
      pharmacotherapy.

PMID- 8875653
TI  - The dialectical approach to understanding and treating borderline personality
      disorder.

PMID- 8875654
TI  - Maximizing abilities: occupational therapy's role in geriatric psychiatry.

PMID- 8875655
TI  - Consumers as employees in mental health: bridges and roadblocks.

PMID- 8875656
TI  - Alcoholism among elderly persons.

PMID- 8875657
TI  - Practice of psychology in a psychiatric hospital.

PMID- 8875658
TI  - Comorbidity and the need for physical examinations among patients seen in the
      psychiatric emergency service.

PMID- 8875659
TI  - A ten-year review of the effect of OBRA-87 on psychotropic prescribing practices
      in an academic nursing home.
AB  - OBJECTIVE: The Omnibus Budget Reconciliation Act of 1987 (OBRA-87) included
      provisions for regulating the use of psychotropic medication, particularly
      antipsychotics, in long-term-care facilities. The study examined the effect of
      OBRA-87 on patterns of prescribing of psychotropic medication in a 514-bed
      nursing home affiliated with a large medical school. METHODS: Computerized
      pharmacy records for the ten-year period from March 1984 through July 1994 were
      retrospectively reviewed to identify orders written for psychotropic medications
      and to determine the percentage of nursing home residents who received
      prescriptions for those agents and the average daily dose of the most frequently
      prescribed agents. RESULTS: During the period before implementation of the
      regulations, the percentages of residents who received antidepressants,
      anxiolytic and sedative-hypnotic medications, and antipsychotic medications were
      stable. After implementation, prescription of antidepressants increased
      significantly, coinciding with a reduction in prescription of anxiolytics and
      sedative-hypnotics and a substantial decrease in prescription of antipsychotics.
      The total number of residents who received any type of psychotropic medication
      decreased, and over time a trend toward prescription of agents recommended for
      geriatric use, such as short-acting benzodiazepines and tertiary tricyclic
      antidepressants, emerged. CONCLUSIONS: The changes that resulted from the OBRA-87
      regulations reffect both the restrictions placed on classes of medication and the
      prevalence of psychiatric disorders in the nursing home. In this facility, OBRA
      87 appears to have served as an impetus for clinical review and change in
      practice style.

PMID- 8875661
TI  - Ten-year use of hospital-based services by geriatric veterans with schizophrenia
      and bipolar disorder.
AB  - OBJECTIVE: To increase understanding of the needs of elderly patients with
      serious mental illness, the study analyzed and compared use of hospital-based
      services by geriatric patients with bipolar disorder and schizophrenia. METHODS:
      The sample consisted of 23 patients with bipolar disorder and 49 patients with
      schizophrenia age 65 or older admitted to the Cleveland Veterans Affairs Medical
      Center over a two-year period. Patients' charts were reviewed to assess
      psychiatric and medical hospitalizations over the past ten years. Comorbid
      medical diagnoses, prescription patterns, and competency status were also
      reviewed. RESULTS: Patients in both diagnostic groups used inpatient services
      relatively frequently, with a mean of four hospitalizations in ten years. Length
      of stay among patients with schizophrenia (mean = 58.2 days) was almost twice as
      long as that of patients with bipolar disorder. Hospitalization for medical
      reasons was infrequent. Mood-stabilizing medications, usually lithium, were
      prescribed to most patients with bipolar disorder, and antipsychotics were
      prescribed to most patients with schizophrenia and less than half of the patients
      with bipolar disorder. More than half of the patients with schizophrenia had
      legal guardians, but few patients with bipolar disorder did so. CONCLUSIONS:
      Findings of this and other studies suggest that although the prognosis for
      persons with serious mental illnesses may have improved over the last several
      decades, these illnesses do not "burn out" in older adults. Elderly patients
      continue to make frequent use of inpatient psychiatric hospitalization and
      pharmacological interventions.

PMID- 8875660
TI  - Clinicians' judgement of capacity of nursing home patients to give informed
      consent.
AB  - OBJECTIVE: The study determined the rate of incapacity to give informed consent
      for medical treatment among patients admitted to a nursing home and assessed
      whether clinical staff members recognized this incapacity and whether they used
      alternative means to provide surrogate decision making for their patients'
      treatment. METHODS: After 44 patients admitted to a nursing home affiliated with
      a major teaching hospital gave oral consent, two standardized tests, the Hopkins
      Competency Assessment Test (HCAT) and the Mini Mental State Examination (MMSE)
      were administered to them. Later a researcher blind to the test results reviewed
      subjects' clinical records to determine whether staff recognized any incapacity
      in giving informed consent for medical treatment. RESULTS: Twenty of 44 subjects
      were identified by the HCAT as incompetent to give informed consent for medical
      treatment. Clinical staff had identified 13 of those subjects as clinically
      incompetent. None of the subjects whom clinical staff identified as clinically
      incompetent was provided with surrogate decision makers in accordance with
      procedures outlined in state law. CONCLUSIONS: The prevalence of incapacity to
      give informed consent in the nursing home population was high. Clinical screening
      by staff did not identify all clinically incompetent patients, and staff had
      unresolved conflicting opinions about individual patients' capacity to give
      informed consent. Even when staff recognized a patient's incapacity to give
      informed consent, proper legal procedures for appointing surrogate decision
      makers were not followed.

PMID- 8875662
TI  - Is psychotherapy ever medically necessary?
AB  - The concept of medical necessity has its roots in payers' fear that mental health
      care will be overused by those with access to it. The author argues that such a
      fear was reinforced by practice patterns that were dominant before the advent of
      managed care, when large amounts of treatment were given to few patients, and
      receipt of such care was poorly correlated with clinical need. He reviews
      differences between traditional models of care and those that have emerged since
      the advent of managed care and prospective payment. Care is medically necessary
      when a diagnosable disorder exists and the patient has impaired function or is
      clinically unstable as a result and when treatment is demonstrably efficacious in
      restoring normalcy or reducing disability. The author describes how psychotherapy
      meets these criteria under three circumstances: when used as an adjunct to
      treatment strategies with demonstrated efficacy, when its efficacy alone is
      established for a given disorder, and as a "holding operation" when no effective
      treatment exists or is agreed to exist. New approaches, including brief or
      intermittent focused treatment, that reduce reliance on the use of treatment as a
      holding operation are described.

PMID- 8875663
TI  - Does managed care permit appropriate use of psychotherapy?
AB  - The author reviews the history of the development of managed care, the
      restrictions it has placed on psychiatric treatments, including psychotherapy,
      and the concerns it has raised about access to and quality of care. He discusses
      research studies documenting that psychotherapy is a fundamental component of
      psychiatric treatment and that it must be included in all health plans and
      organized systems of care. Several false beliefs about the use and cost of
      psychotherapy are considered, such as that dyadic psychotherapy is based on
      abreaction, a technique that Freud abandoned, and that costs for psychotherapy
      will skyrocket if it becomes universally accessible. Research has indicated that
      inappropriate limitations on psychotherapy in prepaid settings lead to poor
      mental health outcomes. The author emphasizes that cost-based constraints on
      established psychiatric treatments are not acceptable until carefully constructed
      scientific outcome studies demonstrate that the use of such constraints does not
      lead to adverse consequences.

PMID- 8875664
TI  - Physical disorders among Southeast Asian refugee outpatients with psychiatric
      disorders.
AB  - OBJECTIVE: The study assessed the prevalence and duration of axis III physical
      disorders and the resulting level of disability among Southeast Asian refugee
      outpatients with axis I psychiatric disorders. METHODS: A total of 266
      consecutive patients who were evaluated in a psychiatric outpatient clinic were
      assessed for the presence of axis III conditions through questions about physical
      symptoms, a medical history and review of records, physical examination, and
      laboratory screening. The sample included 158 Hmong, 58 Laotian, 43 Vietnamese,
      and seven Cambodian patients. RESULTS: Fifty-five percent of the patients had one
      or more axis III disorders, most of which were chronic and were not associated
      with extreme disability. Neurological conditions were most common, and the
      sequelae of war-related trauma were prominent. No associations were found between
      the presence of axis III conditions and age, gender, marital status, or ethnic
      group. In 48 cases, the axis III condition may have caused or exacerbated the
      axis I condition. CONCLUSIONS: Routine medical history and a physical
      examination, including a neurological examination, are recommended for all
      psychiatric patients, including outpatients.

PMID- 8875665
TI  - Substance abuse, community service use, and symptom severity of urban and rural
      residents with schizoprhenia.
AB  - OBJECTIVE: This study examined the relationships of substance abuse, use of
      community-based services, and symptom severity among rural and urban residents
      with schizophrenia in the six months after discharge from short-term inpatient
      care. METHODS: At baseline and six-month follow-up, symptom severity of 139
      subjects was assessed using the Brief Psychiatric Rating Scale (BPRS), and
      substance abuse status was determined using the Structured Clinical Interview for
      DSM-III-R (SCID). Subjects' reports of mental health service use were confirmed
      by record review. RESULTS: Although, on average, BPRS scores indicated symptom
      improvement between baseline and follow-up, symptoms worsened for 27 percent of
      subjects. Multivariate analysis, adjusted for baseline symptom severity,
      indicated poorer outcomes for rural residents, substance abusers, and subjects
      who did not use community services. Symptoms of rural substance abusers who used
      no community services were worse at follow-up than those of any other subgroup.
      Nearly half of all subjects had less than monthly contact with community
      services. The greater likelihood of symptom worsening among rural residents was
      attributed to their less frequent use of community services. CONCLUSIONS: The
      findings reinforce the importance of ensuring involvement in community-based
      services for individuals with comorbid schizophrenia and substance use disorders.
      Promotion of service use by persons with a dual diagnosis may be particularly
      critical to the well-being of rural residents with schizophrenia.

PMID- 8875666
TI  - Length of inpatient stay and recidivism among patients with schizophrenia.
AB  - OBJECTIVE: The study examined whether length of hospital stay is related to
      recidivism among psychiatric patients. A quasi-experimental approach was used to
      address limitations of controlled and epidemiological research. METHODS: Three
      matched groups, each consisting of 55 inpatients with schizophrenia, were
      selected from public psychiatric units with different mean lengths of stay.
      Regression models were used to compare the groups on three variables: time to
      first readmission (survival analysis), number of readmissions (ordinal logit
      regression), and total time in the community in the postdischarge year (multiple
      linear regression). RESULTS: An analysis based on the units with different
      lengths of stay, which was similar to that typically used in controlled studies,
      found no differences in the three outcome measures. However, a second analysis
      that examined data for all patients irrespective of their unit assignment found
      that inpatients treated for 30 days or less relapsed sooner than those with stays
      longer than 30 days. The disparity in results was largely due to overlapping
      quasi-experimental conditions: many patients on the short-stay units had a long
      lengths of stay, and vice versa. The first analysis supports an administrative
      policy of short stays. The second reinforces previous findings that a group of
      patients, primarily young males with onset of illness at an early age and
      multiple previous hospitalizations, is at greater risk of relapse with short-term
      treatment. CONCLUSIONS: The apparent contradiction between a unit- or patient
      based analysis suggests that unit-based results should be interpreted with
      caution when used to make clinical or utilization review decisions.

PMID- 8875667
TI  - Tardive dyskinesia associated with fluoxetine.
AB  - Three cases in which patients who were taking fluoxetine for relief of depression
      showed patterns of abnormal movements suggestive of tardive dyskinesia are
      presented. In the first case, abnormal facial movements began four weeks after
      fluoxetine was added to doxepin and lithium and remitted after fluoxetine was
      discontinued. In the second case, abnormal movements of the mouth and hands were
      noticed four years after the patient started taking fluoxetine and continued to
      be present a year after withdrawal of the medication. In the third case,
      orofacial dyskinesia that had remitted after withdrawal of sertraline and
      paroxetine and reappeared with fluoxetine was still present eight months after
      fluoxetine was withdrawn.

PMID- 8875668
TI  - Help seeking by immigrant Indochinese psychiatric patients in Sydney, Australia.
AB  - To better understand factors contributing to underutilization of mental health
      treatment services by Asian immigrants in English-speaking countries, the authors
      compared the pathways to treatment of 30 psychiatric patients born in Indochina
      who currently resided in Australia and 30 Australian-born patients. A
      semistructured interview was used to gather data on time between onset of
      psychiatric symptoms and treatment in the first and most recent illness episodes.
      Indochinese patients took longer to receive psychiatric treatment for their first
      episode and tended to receive initial help from family members or traditional
      healers. This effect had disappeared by the time of the patient's current
      episode. The results suggest the need for culturally relevant psychiatric
      services for recent immigrants.

PMID- 8875669
TI  - Shortening length of stay without increasing recidivism on a university
      affiliated inpatient unit.
AB  - The impact of reducing length of stay on readmission rates was examined for
      privately insured patients treated on a traditional inpatient unit or in an
      alternatives program with a shorter stay and a continuum of acute care. Billing
      data were analyzed for length of stay and readmission rates for all admissions
      between 1985 and 1992 (N = 1,363). The traditional unit was reorganized in 1990
      into the alternatives program. Although the program decreased mean length of stay
      from 20.2 days to 6.2 full-day equivalents, overall readmission rates did not
      increase (17.2 percent, compared with 18.6 percent for the traditional unit).
      Rates increased for a subgroup of patients with psychotic disorders (from 13.7 to
      35.2 percent).

PMID- 8875670
TI  - Feigned psychiatric symptoms in the emergency room.
AB  - Psychiatrists providing emergency services at an urban general hospital completed
      questionnaires on 227 patients evaluated over a two-month period to assess
      whether they suspected the patient of malingering or of having secondary gains,
      and whether the patient was confronted about the suspicions. Thirteen percent of
      patients were strongly or definitely suspected of feigning symptoms; none
      received a primary diagnosis of malingering, and less than half were confronted.
      Suspected secondary gains included food and shelter, medications, financial
      gains, and avoidance of jail, work, or family responsibilities.

PMID- 8875671
TI  - Memories of Metropolitan.

PMID- 8875672
TI  - Psychiatric evaluation in a second language.

PMID- 8875673
TI  - Biomedicine: key to parity coverage?

PMID- 8875674
TI  - Survey finds two-thirds of insured Americans are enrolled in managed behavioral
      health programs.

PMID- 8875675
TI  - CMHS report traces dramatic growth in staffing in mental health organizations
      over two decades.

PMID- 8875676
TI  - Joseph Trueta: Catalan surgeon and medical researcher.

PMID- 8875677
TI  - Lipid peroxidation and antioxidant defense mechanisms in rat renal tissue after
      daunorubicin administration.
AB  - Redox cycling compounds such as daunorubicin have been assumed to be toxic
      because they stimulate reactive oxygen-mediated lipid peroxidation. Furthermore,
      both DT-diaphorase and glutathione (GSH) have been regarded as protective
      cellular compounds against daunorubicin cardiotoxicity, but their role in
      daunorubicin nephrotoxicity remains unclear. To investigate this issue, 10 adult
      Wistar rats were twice injected with a single dose of 20 mg/kg body weight
      daunorubicin into the tail vein; the interval between injections was 48 h. A
      control group of 10 rats were injected with normal saline. One day after the
      second injection, all the animals were sacrificed and their kidneys were analyzed
      for malondialdehyde (MDA) as an index of lipid peroxidation, DT-diaphorase
      activity, and GSH and glutathione disulphide (GSSG) content. A significant
      increase of MDA concentration (2.41 vs. 1.64 p < 0.001) and DT-diaphorase
      activity (0.2 vs. 0.12, p < 0.001) was found in the renal tissue of daunorubicin
      injected rats. In contrast, GSH and GSSG levels were decreased in those animals
      (566 vs. 1282, p < 0.001 and 115 vs 187, p < 0.01, respectively). The results of
      this study give evidence that a high dosage of daunorubicin induces lipid
      peroxidation in renal tissue of rats stimulating the activation of DT-diaphorase
      and the detoxificative depletion of GSH.

PMID- 8875678
TI  - Lipid peroxidation after acute renal ischemia and reperfusion in rats: the effect
      of trimetazidine.
AB  - Lipid peroxidation is a critical pathway of reactive oxygen species inducing
      tissue injury in postischemic acute renal failure. In order to evaluate the
      effect of renal ischemia reperfusion on kidneys, renal tissue malondialdehyde
      (MDA, nmol/g wet weight) concentration was measured in 29 male Wistar rats
      subjected to a midline abdominal incision and 60 min occlusion of the left renal
      artery. A right nephrectomy was performed at the beginning of the ischemic
      period. The animals were separated in four groups. Groups 1 (n = 7) and 3 (n = 7)
      underwent 60 min of ischemia and 15 min of reperfusion, respectively. Groups 2 (n
      = 8) and 4 (n = 7) were subjected to the same procedure but, in addition, they
      received 2.5 mg/kg TMZ into the tail vein 2 h prior to the left renal artery
      occlusion. A significant elevation of MDA after 60 min of ischemia (1.43 vs. 2.1,
      p < 0.001), which was augmented after 15 min of reperfusion (1.4 vs. 3.72, p <
      0.001) was observed. Furthermore, there was a significant reduction of renal
      tissue MDA in ischemic rats treated with TMZ (group 3) (2.1 vs. 1.52, p < 0.001).
      The maximum reduction of renal tissue MDA was observed in ischemic-reperfused
      rats (group 4) that had received TMZ (3.72 vs. 1.36, p < 0.001). It is suggested
      that lipid peroxidation is a critical event in postischemic acute renal failure,
      and TMZ is a useful protective agent of renal damage from oxygen free radicals.

PMID- 8875679
TI  - Endothelin-1 in acute renal failure.
AB  - To study the pathological significance of circulating endothelin (ET) in ARF, we
      measured plasma ET in seven children (mean age 8.8 +/- 4.4 years) with ARF in the
      most severe phase and 3.7 +/- 3.5 months later in the recovery period. Twenty
      seven healthy children were included in the study as controls. Plasma ET level
      was measured by highly sensitive and specific radioimmunoassay for ET-1 and ET-2
      (ET-1/2, Biomedica, Vienna). Plasma ET was significantly higher in the most
      severe phase of ARF (4.75 +/- 4.08 fM/ml) than in the recovery period (0.78 +/-
      0.24 fM/ml; p < 0.01), but comparing to plasma ET in the healthy children, the
      difference was only of borderline statistical significance (Pf, 0.0573). Since
      plasma concentrations of creatinine did not correlate with plasma ET in patients,
      either in acute or in the recovery phase of disease, we concluded that decreased
      GFR is not the main factor determining an increased ET in ARF. We suggest that
      elevated plasma ET in ARF may be secondary to vascular endothelial dysfunction
      and speculate that enhancement synthesis of endothelial relaxing factor (EDRF)
      inhibits ET synthesis during the recovery period. We did not find any
      relationship between plasma ET and blood pressure (BP) in patients with ARF, so
      we conclude that circulating ET is not the main factor determining BP in ARF.

PMID- 8875680
TI  - Renal dysfunctions in glomerulonephropathy with rapidly declined renal failure.
AB  - Eight patients aged between 5 and 26 years developed rapid deterioration of renal
      function and became oliguric/anuric with duration ranging from 1 to 21 days. The
      initial functional assessment revealed severe degree of glomerular, tubular, and
      vascular dysfunctions. The magnitude of renal dysfunction was quantified and
      expressed in terms of a clinical score. The degree of glomerular and tubular
      dysfunctions were inversely proportional to the renal plasma flow and peritubular
      capillary blood flow (PTCB), respectively. Similar findings have been observed in
      a variety of severe glomerulonephropathies. In this aspect, it is likely that the
      reduction of peritubular capillary blood flow and tubulointerstitial disease are
      interrelated. Further evidence to support the primary role of reduction of PTCB
      in inducing tubulointerstitial disease is provided by the following: (a)
      Reduction of PTCB is documented in mesangial proliferative nephrosis with steroid
      resistance prior to the detection of tubulointerstitial disease. (b) Ischemic
      insult can induce tubulointerstitial disease in experimental setting of renal
      artery occlusion in animal, (c) Improved tubular function can be achieved
      following the increase in PTCB with the enhanced renal perfusion therapy.

PMID- 8875681
TI  - Scleroderma renal crisis is still a life-threatening syndrome.
AB  - Scleroderma renal crisis (SRC) was known as a rare and catastrophic syndrome
      responsible for acute renal failure (ARF) in a context of widespread
      microvascular disease occurring in progressive systemic sclerosis (PSS).
      Following pathogenetic hypoteses, angiotensin converting enzyme (ACE) inhibitors,
      plasma infusions (PI), and plasma-exchange (PE) have been employed in SRC with
      favorable results. Our purpose was to verify whether these therapies have
      consistently changed the fatal prognosis of SRC, even in our experience. In the
      last 10 years, SRC was diagnosed in eight patients (all eight with histologic
      data). The first five cases were treated with steroids, antihypertensive
      cocktail, and PI: all five died, two within 48 hours, three after 10, 15, and 300
      days, respectively. Three other patients were treated with ACE inhibitors, PI,
      and PE: all three died after 1, 9, and 12 months of HD. Clinical-histological
      correlations showed a strong relationship between the extent of glomerular
      involvement and the degree of renal failure, while arterial lesions seem to be
      more related to the past history of PSS, independently from the previous
      existence of hypertension. We conclude that "true" SRC diagnosed by restrictive
      criteria is still a rare life-threatening syndrome, and, unfortunately, no clear
      predictive biochemical or clinical signs could be identified; vascular renal
      involvement correlates to the duration of PSS independently of previous clinical
      evidence of renal failure or hypertension; a glomerular pattern similar to that
      reported for hemolytic-uremic syndrome (HUS)/thrombotic thrombocytopenic purpura
      (TTP) syndrome is directly related to the degree of acute renal involvement; SRC
      may occur even in the absence of hypertension, mainly if cardiomyopathy is
      present: in our experience. ACE inhibitors and plasma therapies have changed the
      short-time prognosis of SRC, but they may be unable to provide recovery from
      dialysis and do not avoid further evolution of extrarenal PSS exiting in late
      death.

PMID- 8875682
TI  - Is pregnancy-related acute renal failure a disappearing clinical entity?
AB  - The actual disappearance of pregnancy-related acute renal failure (PR-ARF) is a
      common "feeling" for nephrologists. The aim of this study was to exactly quantify
      this event by evaluating epidemiology and the extent of renal damage in PR-ARF.
      From 1958 to 1994, 84 cases of PR-ARF were observed (5.8% of total number of ARF
      needing dialysis). In four successive periods (1956-67, 1968-77, 1978-87, 1988
      94), the incidence of PR-ARF fell from 43% to 0.5% with respect to the total
      number of ARF, and from 1/3000 to 1/18,000 with respect to the total number of
      pregnancies. Maternal mortality in the past was high (31%), but no cases of death
      in the last period were seen. Irreversible renal damage was recorded in 11.1% of
      PR-ARF, and, in particular, in 18.7% of cases of preeclampsia-eclampsia (PE-E).
      The worst maternal and renal prognosis occurred in PE-E that was complicated by
      abruptio placentae (AP). Neither disseminated intravascular coagulation (DIC),
      microangiopathic hemolytic anemia, nor prostacyclin imbalance were significantly
      related to the severity of renal damage. Heparin therapy did not modify DIC
      evolution and renal outcome and was aggravated by severe hemorragic
      complications. Support therapy with plasma infusion, antithrombin III, and
      antiplatelet agents seems to be helpful. In conclusion, PR-ARF has become a rare
      occurrence and, in our experience, no cases of death or irreversible renal damage
      were observed in the last 7 years. The most important reasons for this favorable
      evolution seem to be an improved medical care and more effective measures of
      careful prevention, mainly regarding tempestive delivery.

PMID- 8875683
TI  - A simple prognostic index for patients with acute renal failure requiring
      dialysis. French Multicentric Prospective Study on Furosemide in Acute Renal
      Failure Requiring Dialysis.
AB  - The probability of death in patients with acute renal failure (ARF) remains high.
      A valid prognostic index available on patient admission and during follow-up
      could be helpful for decision making. In this study, 94 ARF patients requiring
      dialysis (not responding to a previous single dose of furosemide 15 mg/kg) were
      included. On admission, patients were classified according to a Simplified Acute
      Physiology Score (SAPS) of < or = 15 or > 15. The prognostic value of 11 risk
      factors was analyzed. Only 6 in 11 risk factors were significant by univariate
      analysis: age (> 55 years) (0.02), mechanical ventilation (0.008), oliguria (<
      500 mL/day during the first 5 days) (0.02), sepsis (0.001), shock (0.007), and
      serum bilirubin (> 30 mumol) (0.001). Only oliguria and sepsis were significant
      risk factors by multivariate analysis. Overall mortality rate was 41%. Mortality
      rate was higher in patients with SAPS > 15 (65%) than in those with SAPS < or =
      15 (22%) (0.001). Patients with > 3 risk factors showed a significantly higher
      mortality rate than patients with < 3 risk factors (all patients disregarding
      SAPS) (0.001). Considering the worst combination of risk factors by univariate
      analysis, mortality prediction was 56% if oliguria, sepsis, and high serum
      bilirubin were present, and reached 80% if an older age was added (four risk
      factors). Ventilation increased probability of death to 92% (five risk factors).
      If all six risk factors were present, the probability rose to 96%. The
      corresponding observed mortality rate was 32% for three risk factors, 70% for
      four, 81% for five and 100% for six risk factors. The results suggest that
      probability of death in ARF requiring dialysis can be correctly estimated when
      more than three significant risk factors are present. If confirmed, they could
      avoid using a more complex severity scoring system in patients with ARF requiring
      dialysis.

PMID- 8875684
TI  - Etiology and prognosis in 438 patients with acute renal failure.

PMID- 8875685
TI  - Mortality in elderly patients with acute renal failure.
AB  - In a retrospective study, we identified 55 elderly patients with acute renal
      failure (ARF) admitted to our hospital during an 8-year period from 1985 to 1993.
      Information about the etiology, complications, laboratory data, and treatment
      course were obtained from the clinical history. Of the 200 patients with ARF
      admitted to the hospital during this period, 28% were patients more than 60 years
      old (41 male and 14 female) with an average age of 68.5 +/- 7 years. The main
      causes of ARF were sepsis, volume depletion, low cardiac output, arterial
      hypotension, nephrotoxicity by antibiotics, and obstructive uropathy. The global
      mortality of elderly patients with ARF was 53%. The mortality rate of the
      different types of the ARF were: prerenal 35%, intrinsic 64% (oliguric 76%,
      nonoliguric 50%), and postrenal 40%. Mortality as a result of sepsis occurred in
      18 patients (62%), by cardiovascular disease in 4 patients (13%), by acute
      respiratory failure in 2 patients (7%), and by other causes in 5 patients (18%).
      In the cases of sepsis, Pseudomonas was detected in 7 cases (39%), Escherichia
      coli in 2 cases (11%), Gram-negative nonspecific in 3 cases (17%), Klebsiella in
      1 case (5%), and in 5 cases (16%), the hemoculture was negative. The patient
      survival rate was 47% (26 of 55 patients). Of these patients, 19 recovered their
      normal renal function (73%), but 7 patients remained with renal failure (27%). In
      conclusion, the global mortality in the elderly patients without considering the
      types of ARF was 53%. The oliguric form had the highest mortality rate with 76%.
      The main causes for mortality were sepsis with 62%, cardiovascular disease with
      13%, and other causes 18%.

PMID- 8875686
TI  - Acute renal failure in polytraumatized patients: prediction of outcome.
AB  - Prediction of outcome of acute renal failure (ARF), particularly in patients with
      multisystem organ failure (MSOF), is a very important issue and a very difficult
      task. In patients with ARF as a consequence of severe polytrauma, frequent
      complications (e.g., sepsis, respiratory insufficiency, DIC, hepatic
      insufficiency, etc.) contribute to a hyperbolic state, and in the case of
      synergistic action, they start the mechanism of MSOF. In 33 patients (1 female,
      32 male, 38.61 +/- 8.79 years) with severe polytrauma acquired in war combat, ARF
      developed requiring hemodialysis (HD) treatment. Seventeen out of 33 (51.4%)
      recovered renal function. In 12 out of 33 patients, MSOF occurred with less
      successful recovery results. The analysis of pathophysiologic mechanisms of MSOF
      appearance and ARF outcome has shown the importance of blast injuries, bowel
      injury, respiratory insufficiency requiring assisted ventilation, and sepsis.
      Although severe hemorrhage and shock are the common mechanism of ARF appearance
      in these patients, it seems that wounds by themselves can be of great importance,
      as abdominal wounds are more frequently associated with ARF and MSOF than in
      other types.

PMID- 8875687
TI  - Validity of prediction scores in acute renal failure due to polytrauma.
AB  - During a 36-month period from 1992 to 1994, 33 patients with severe polytrauma
      acquired in war combat (1 female, 32 male, 38.61 +/- 8.79 years) developed acute
      renal failure (ARF) which required hemodialysis (HD) treatment. In 12 patients,
      multiple system organ failure (MSOF) occurred as a complication of either general
      conditions or septic complications. In 17 patients (51.4%), and in 3 patients
      with MSOF, recovery of renal function occurred. We compared the outcome of ARF
      and several predictive scores (APACHE II and ATNISS). The APACHE II score did not
      correlate with the outcome of ARF, and ATNISS significantly correlated with the
      outcome of ARF. The maximum value of ATNISS in the patients with lethal outcome
      was 1.004, and the minimal value with the same outcome was 0.182. Although ATNISS
      is a very good score of severity, it seems to underestimate very influential
      factors in patients with severe polytrauma with ARF (MSOF, mechanism of trauma).

PMID- 8875688
TI  - Acute renal failure complicating severe acute pancreatitis.
AB  - The records of 563 patients admitted to the hospital with diagnosis of acute
      pancreatitis have been studied retrospectively. The aim of the study was to
      investigate the prevalence of acute renal failure (ARF) in these patients, and to
      evaluate the most important risk factors for ARF development and mortality. The
      prevalence of ARF in studied population was 14%, but only 3.8% of ARF patients
      with acute pancreatitis had isolated renal failure. Other patients had additional
      failure of other organ systems, 68.4% of whom had multiorgan failure (MOF) before
      the onset of ARF. In only 8.9% of ARF patients was the renal system the first
      organ system to fail. Patients with ARF were significantly older, had more
      preexisting chronic diseases (including chronic renal failure), usually had MOF,
      and local pancreatic complications relative these in the group with normal renal
      function. The development of ARF was directly influenced by severity of acute
      pancreatitis. The mortality rate in ARF patients was 74.7%, compared to an 7.4%
      mortality of patients with acute pancreatitis and normal renal function.
      Preexisting chronic disease, the presence of MOF and their number, local
      pancreatic complications, and older age of the patients increased mortality in
      ARF patients. The prognosis of patients with oliguric ARF requiring renal
      replacement therapy was extremely poor, indicating the importance of prevention
      of ARF in the patients with acute pancreatitis.

PMID- 8875689
TI  - Acute renal failure as a complication of acute pancreatitis.
AB  - To assess the prevalence of acute renal failure (ARF) in patients with acute
      pancreatitis, as well as the factors predictive of a lethal outcome, we
      retrospectively studied the data of all patients admitted to our hospital over a
      5-year period. Between 1989 and 1993, 554 patients presented with acute
      pancreatitis, of which 24 (4.4%) subsequently developed ARF. Death occurred in
      14/24 (58%) of patients with ARF, and was associated with an increased incidence
      of multiorgan failure. There was no statistically significant difference in the
      age, admission blood pressure, or admission pulse rate of the patients who
      survived and those who died. In contrast, death was associated with a higher
      Ranson score, and the increased prevalence of multiorgan failure. The length of
      hospitalization of the nonsurviving group was significantly shorter. Acute renal
      failure is not a common finding in patients with acute pancreatitis. However,
      when it occurs, it is associated with a poor prognosis, and is predicted by a
      higher Ranson score and the presence of multiorgan failure.

PMID- 8875690
TI  - Acute renal failure due to hemorrhagic fever with renal syndrome.
AB  - The aim of our study was to analyze the clinical course and outcome of acute
      renal failure (ARF) in patients with hemorrhagic fever with renal syndrome
      (HFRS). From 1983 to 1995, we treated 33 patients (27 males, 6 females) aged from
      16 to 71 years. Half of patients were connected with work at a farm or in a
      forest. The disease was confirmed serologically with indirect immunofluorescence
      test (IFT) and enzyme-linked immunosorbent assay (ELISA). In 18 patients
      percutaneous kidney needle biopsies were analyzed. In 85% of the cases, the
      disease broke out from June to October. The most frequently expressed clinical
      signs and symptoms were fever, nausea/vomiting, headache, backache, abdominal
      pain, myalgia, diarrhea, conjunctival injection, and hemorrhages. Four patients
      had concomitant pancreatitis. In 25 patients, oliguria was present, and transient
      hemodialysis treatment was needed in 19 patients. Infection with Hantaan virus
      was established in 20 patients and with Puumala virus in 13 patients. At renal
      biopsy, acute interstitial nephritis accompanied with hemorrhages and necrosis
      was found, and at a later biopsy there were also signs of interstitial fibrosis.
      All patients were cured, but renal function was not completely recovered in some.
      We conclude that ARF is a serious complication in patients with HFRS. Although
      not lethal in our group of patients, many of them showed severe signs and
      symptoms of illness. Transient hemodialysis was necessary in two-thirds of the
      patients. Some degree of functional defects and morphological changes might
      persist.

PMID- 8875691
TI  - Protection from the nephrotoxicity of contrast dye.
AB  - Previous studies have reported a 4%-50% incidence of acute renal failure (ARF)
      following the use of radiocontrast media in patients with preexisting chronic
      renal insufficiency. In these studies, ARF was defined as a rise of the serum
      creatinine of at least 1 mg/dl above baseline. Using the same criteria, we
      studied 214 patients undergoing various intravascular radiocontrast media
      procedures. Patients were infused with a specially prepared cocktail solution
      (NSMF) containing 1000 ml half-normal saline, 12.5 g of mannitol (M), I ampule
      NaHCO3, and 200 mg of furosemide (F) at 100 ml/h from one hour prior to two hours
      after the procedure. Urinary output was replaced with normal saline for at least
      6 h after the procedure. Seven percent of the patients developed acute renal
      insufficiency. Only 3% of the patients had a rise in serum creatinine greater
      than 2 mg/dl. No patient required dialysis therapy after the procedure. There was
      one unrelated death caused by acute myocardial infarction postangioplasty. Risk
      factors for development of ARF despite cocktail administration included the
      presence of diabetes mellitus and angiotensin converting enzyme (ACE) inhibitor
      therapy. We concluded that the properly administered NSMF solution protects
      against radiocontrast dye induced renal failure. In select patients with chronic
      renal insufficiency, consideration should be given to withholding ACE inhibitor
      therapy for 24-48 h prior to administration of intravenous radiocontrast dye. A
      large controlled trial will be required to establish whether the NSMF solution
      offers benefit beyond that of saline hydration alone.

PMID- 8875692
TI  - Tubular toxicity is the main renal effect of contrast media.
AB  - The aim of this study is to evaluate the effects of contrast media on both
      tubular and glomerular function. Different parameters of tubular and glomerular
      function were determined before and at 1, 3, and 5 days after the intravascular
      administration of contrast media in 100 adult renal patients (plasma creatinine
      0.6-10.8 mg/dL, mean: 1.3). Urinary activities of five tubular enzymes (alanine
      aminopeptidase, gamma-glutamyltransferase, alkaline phosphatase, lactate
      dehydrogenase, N-acetyl-beta-D-glucosaminidase) increased significantly on the
      first day after the administration of contrast media, indicating a tubular
      damage. Glomerular filtration rate and the conventional tests of glomerular
      function (plasma creatinine, creatinine clearance, and urinary proteins)
      presented only slight variations after the administration of contrast media. In
      conclusion, contrast media principally affected the renal tubule (as demonstrated
      by enzymuria), while their effects on glomerular function were very mild.

PMID- 8875693
TI  - Glomerular and tubular effects of contrast media diatrizoate and iopromide.
AB  - The aim of this study is to evaluate the nephrotoxicity of two contrast media
      (CM), with different physicochemical characteristics: diatrizoate (ionic high
      osmolar), iopromide (nonionic low-osmolar). Intravenous urography was performed
      in 34 patients: 17 were examined with diatrizoate and 17 with iopromide, randomly
      assigned. Different parameters of glomerular and tubular function were measured
      before and at 6, 24, and 48 h after urography. Both contrast media induced a
      reversible increase of urine enzymes, which was significantly higher after
      diatrizoate. In particular, diatrizoate determined a relevant increase of brush
      border enzymes gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) and
      of cytosolic enzyme lactate dehydrogenase (LDH), while, after iopromide increases
      of urinary enzymes were less evident and were significant only for GGT and ALP.
      In addition, diatrizoate affected other tubular functions (clearances of
      phosphorus and uric acid) and slightly decreased glomerular function in a few
      patients. In no case did these glomerular and tubular effects have a clinical
      relevance. In conclusion, the nonionic low-osmolar contrast medium iopromide
      appeared less nephrotoxic than diatrizoate. The cost-benefit ratio needs further
      examination.

PMID- 8875694
TI  - Prognostic indexes and mortality in critically ill patients with acute renal
      failure treated with different dialytic techniques.
AB  - The objective of this study was to compare the evolution of patients with acute
      renal failure (ARF) treated conservatively or with different dialytic techniques
      in an intensive care unit (ICU). From June 1992 to November 1994, 1087
      consecutive patients were admitted in our ICU. Two hundred and twenty of these
      presented with ARF, and were divided into three groups; group I (control group):
      156 patients with ARF who did not receive substitutive techniques; group II: 21
      patients under intermittent hemodialysis (IHD) or peritoneal dialysis (PD); group
      III: 43 patients under continuous hemodiafiltration (CHDF). The studied variables
      were age, etiology of renal failure, requirement of dialysis, type of dialysis,
      length of ICU and hospital stay, and renal function outcome. APACHE II and SAPS
      scores were recorded on admission and analyzed for hospital mortality. Chi-square
      test and the analysis of variance were used for the statistical analysis. Results
      are presented as mean +/- SD. A p value below 0.05 was considered statistically
      significant. Although etiology of ARF was multifactorial, we found a high
      frequency of ARF due to sepsis (56.8%), hypoperfusion (58.7%), and acute tubular
      necrosis (62.5%). Sepsis and heart failure were clinical conditions associated to
      a greater mortality. We did not find any statistical difference between the two
      dialyzed groups for all the studied variables, nor between the three groups
      regarding APACHE II and hospital stay. Significant differences were found between
      dialyzed and non-dialyzed patients respect to age, group I: 64.1 +/- 13.6, group
      II: 56.4 +/- 19.7, and group III: 56.0 +/- 14.1 (p < 0.001), creatinine peak
      serum levels, group I: 260 +/- 130, group II: 494 +/- 209, and group III: 441 +/-
      170 mumol/L (p < 0.0001), and mortality, group I: 46.9%, group II: 66.7%, and
      group III: 76.2% (p < 0.002). SAPS score showed differences between the control
      group and the CHDF group 13.9 +/- 4.8 and 16.4 +/- 5.4 (p < 0.007), respectively.
      The use of dialytic techniques in critically ill ARF patients is associated with
      greater mortality. Prognostic indexes on admission did not correctly classify our
      patients with ARF. Continuous hemodiafiltration does not involve greater
      mortality or length of stay as compared to conventional dialysis.

PMID- 8875695
TI  - Acute renal failure due to traumatic rhabdomyolysis.
AB  - Between 1990 and 1993, we studied 14 cases of acute renal failure due to
      prolonged muscular exercise (e.g., squat jumping, sit-ups) and blunt trauma
      inflicted by law enforcement personnel using sticks or leather belts. None of the
      patients had a prior history of myopathy, neuropathy, or renal disease. All were
      critically ill and required renal support in the form of dialysis. Although the
      morbidity was high, 13 of the patients recovered normal renal function. One
      patient expired due to sepsis.

PMID- 8875696
TI  - Acute renal failure of obstetrical origin during 1994 at one center.
AB  - Although preventable, acute renal failure (ARF) of obstetrical origin continues
      to be common in developing countries. During the year 1994, we treated a total of
      238 cases of ARE. Of these cases, 43 (18%) were of obstetrical origin. All of the
      patients were known to be previously healthy. Acute renal failure occurred in
      association with antepartum hemorrhage in 15, postpartum hemorrhage in 10,
      intrauterine death of fetus in 11, preeclampsia or eclampsia in 9, and septic
      abortions or puerperal sepsis in 7. Thirty-six patients required dialysis therapy
      because of moderate to severe azotemia. Renal histology was studied in 12 cases.
      Acute cortical necrosis was present in 9, extensive tubular necrosis in 2, and 1
      patient had membranoproliferative glomerulonephritis. Twenty-two (51%) patients
      recovered normal renal function, while 11 (26%) developed irreversible renal
      dysfunction and 10 (23%) expired. Mortality and morbidity in this region is still
      quite high in obstetrical situations. Poor health infrastructure and lack of
      antenatal health clinics leads to development of major complications at the time
      of childbirth, which is mostly conducted at home by untrained personnel in quite
      a few cities of the country.

PMID- 8875697
TI  - Predictors of outcome in malarial renal failure.
AB  - We studied 38 patients with acute renal failure (ARF) due to malaria over a 5
      year period between 1990 and 1994 at the Institute of Urology and
      Transplantation. There were 30 males and 8 females who ranged in age from 13 to
      75 years. Most were critically ill on presentation with blood urea levels between
      116 and 587 mg% and serum creatinine concentrations between 3 and 30 mg%. Anemia
      accompanied by hyperbilirubinemia was a result of severe hemolysis. Antimalarial
      therapy consisted of quinine sulfate, chloroquine, or both. Of the 38 patients,
      32 required hemodialysis and eventually recovered normal (n = 29) or near normal
      (n = 3) function. Six patients died.

PMID- 8875698
TI  - Acute renal failure in a patient with bilateral aneurysms of iliac common
      arteries.

PMID- 8875699
TI  - Prevention of cis-platinum nephrotoxicity in a high-risk patient.
AB  - A 64-year-old woman, affected by stage IIIc epithelial ovarian cancer,
      experienced acute renal failure after the first cycle of chemotherapy with
      cyclophosphamide and cis-platinum, despite standard prophylactic measures of
      hydration-diuresis. In this paper we report data obtained during 5 additional
      cycles of chemotherapy. The schedule of treatment was modified by dividing
      standard dose of cis-platinum by three and administering this divided dose for 3
      days. The following five cycles of treatment did not cause a clinically relevant
      impairment of glomerular function or evident tubular toxicity. A high-risk
      patient was treated safely combining hydration-diuresis measures with lengthening
      of cis-platinum administration over 3 days.

PMID- 8875700
TI  - Evidence that both ETA and ETB receptor subtypes are involved in the in vivo
      aldosterone secretagogue effect of endothelin-1 in rats.
AB  - Endothelins (ET) are a family of vasoconstrictor peptides, secreted by vascular
      endothelium, which act through two main subtypes of receptors: ETA and ETB. ET-1
      is known to stimulate aldosterone (ALDO) secretion by adrenal zona glomerulosa
      (ZG), and in vitro its effect was recently found to be exclusively mediated by
      ETB receptors. In this study the involvement of ETA and ETB in the mediation of
      the in vivo acute ALDO secretagogue action of ET-1 was investigated by the use of
      their selective antagonists BQ-123 and BQ-788, respectively. The bolus
      intraperitoneal administration of ET-1 dose-dependently raised both basal and
      angiotensin II (ANG II)-enhanced plasma ALDO concentration (PAC) in rats. Both
      antagonists counteracted the stimulatory effect of ET-1 on basal PAC, and when
      administered together completely annulled it. Conversely, only BQ-788 reversed
      the effect of ET-1 on ANG II-enhanced PAC. ET-1 increased systolic blood pressure
      (BP) in normal rats, but not in animals simultaneously administered ANG II. The
      hypertensive effect of ET-1 was completely abolished by BQ-123, and not affected
      by BQ-788. In light of these findings the following conclusions can be drawn: (i)
      the in vivo ALDO secretagogue action of ET-1 is mediated by both ETA and ETB,
      this latter subtype of ET receptors playing a major role; and (ii) the mechanism
      whereby ETA participates in this in vivo effect of ET-1 is indirect, and probably
      connected with the ET-1-induced rise in BP and adrenal blood flow.

PMID- 8875701
TI  - Time-course changes in serum cytokine levels in two experimental acute
      pancreatitis models in rats.
AB  - Activated leukocytes and cytokines have important roles in the multi-system
      involvement during acute pancreatitis. The changes in the serum level of tumor
      necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) over time were
      investigated in two experimental acute pancreatitis models in rats. Mild
      edematous pancreatitis was induced with an overdose of cholecystokinin
      octapeptide (CCK-8), while a severe hemorrhagic form of pancreatitis was induced
      by ligation of the common bilio-pancreatic duct. The rats were examined 2, 4, 8,
      16, 24 and 48 h after pancreatitis induction. The severity of the inflammation
      was assessed by measurement of the serum amylase activity, quantification of the
      edema, and histological examination. Serum TNF-alpha and IL-6 were determined by
      bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines,
      respectively. In CCK-8-induced acute pancreatitis, the pancreatic weight/body
      weight ratio (pw/bw) and amylase level were significantly elevated at 2 h, and
      the maximum levels were observed at 4 h (8.19 +/- 1.13 mg/g and 69.4 +/- 12.8 x
      10(3) U/ml, respectively). Both parameters subsequently decreased continuously
      during the observation period. The serum IL-6 level was significantly increased
      at 4 h relative to the controls (123.3 +/- 5.8 vs 37.5 +/- 15 pg/ml), and then
      decreased continuously. In this model, only a moderate level of serum TNF-alpha
      was observed at 2 h. In the biliary type of acute pancreatitis, the ratio pw/bw
      increased continuously during the study and reached the maximum level at 48 h
      relative to the sham-operated control (8.8 +/- 1.4 vs 5.3 +/- 0.8 mg/g). The
      serum amylase level was significantly elevated at 2 h (43.2 +/- 13 x 10(3) U/ml),
      but then decreased continuously. The serum IL-6 reached its maximum level at 16 h
      (3800 +/- 447 pg/ml). In this model, increased TNF-alpha levels (75-300 U/ml)
      were measured 8, 16 and 24 h after pancreatitis induction. The results led to
      correlations between the serum IL-6 levels and the biochemical and morphological
      severity of acute pancreatitis in both experimental models. The data suggest that
      IL-6 and TNF-alpha may participate in the pathogenesis of these types of acute
      pancreatitis.

PMID- 8875702
TI  - Histomorphological confirmation of bone loss in the femoral-metaphyseal tissues
      of rats with skeletal unloading.
AB  - The alteration of mineral content in the femoral metaphysis of rats with skeletal
      unloading was investigated using a model of hindlimb suspension. Animals were fed
      for 4 days during the unloading. The femoral length, femoral dry weight and
      femoral mineral density were significantly decreased by the unloading. The
      calcium, phosphorus and zinc contents in the femoral metaphysis were appreciably
      reduced by the unloading, although, except for zinc, similar decreases were not
      seen in the femoral diaphysis. Moreover, the trabecular bone at the femoral
      metaphysis was clearly reduced by the unloading. Skeletal unloading caused a
      decrease in osteoid tissue in the primary and secondary spongiosa, indicating
      that osteoblastic bone formation may be inhibited. The present results clearly
      demonstrate that skeletal unloading can induce bone loss in the femoral
      metaphysis.

PMID- 8875703
TI  - Effect of vitamin K2 (menaquinone-7) on bone metabolism in the femoral
      metaphyseal tissues of normal and skeletal-unloaded rats: enhancement with zinc.
AB  - The effect of vitamin K2 (menaquinone-7) on bone metabolism in the femoral
      metaphyseal tissues of normal and skeletal-unloaded rats was investigated.
      Skeletal unloading was designed using a model of hindlimb suspension; the rats
      were fed for the 4 days of unloading. The metaphyseal tissues obtained from
      normal and skeletal-unloaded rats were cultured for 48 h in medium containing
      either vehicle or vitamin K2 (10(-6) and 10(-5) M). The presence of vitamin K2
      (10(-5) M) caused a significant increase in alkaline phosphatase activity and
      calcium content in the metaphyseal tissues from normal rats. Such an effect was
      not seen in the bone tissues from skeletal-unloaded rats. Additionally, the
      presence of zinc sulfate (10(-5) M) in effective concentration produced a
      significant increase in alkaline phosphatase activity and calcium content in the
      metaphyseal tissues from normal and skeletal-unloaded rats. In the presence of
      vitamin K2 (10(-5) M), the stimulatory effect of zinc sulfate on bone calcium
      content was appreciably enhanced; although this effect was completely abolished
      by cycloheximide (10(-6) M), an inhibitor of protein synthesis. This study
      demonstrates that the effect of vitamin K2 (menaquinone-7) on trabecular bone
      calcification in rats with skeletal unloading-induced osteopenia is enhanced by
      zinc in vitro. The enhancement with zinc may be based on a newly synthesized
      protein in the bone tissues.

PMID- 8875704
TI  - Combined effects of caffeine and alcohol during pregnancy on bones in newborn
      rats.
AB  - The combined effects of caffeine and alcohol on mineral contents of fetal
      mandibles and femurs were studied. Pregnant rats were divided into four groups:
      group 1, control; group 2, caffeine; group 3, alcohol; and group 4, caffeine-plus
      alcohol. Alcohol (1.0 g ethanol/kg body weight) was intubated twice daily,
      beginning at day 9 of gestation. Caffeine (2 mg/100 g body weight) was given as a
      dietary supplement. Groups 1 and 2 were intubated with isocaloric sucrose
      solution. At birth, randomly selected pups were killed and the mandible and femur
      were removed and dried. Ca, P, Mg, Zn and hydroxyproline in these bones were
      measured. Notwithstanding the dams' intake of caffeine and alcohol administered
      separately, the present results suggest that the combination of caffeine and
      alcohol exhibited the most detrimental effects.

PMID- 8875705
TI  - Effect of aluminum on regional brain antioxidant defense status in Wistar rats.
AB  - This investigation gives a detailed analysis of oxidative stress conditions
      generated following chronic aluminum exposure (10 mg Al/kg body weight per day)
      for a period of 4 weeks. We observed a significant enhancement in the levels of
      lipid peroxidation at the completion of aluminium treatment. The antioxidant
      enzymes, superoxide dismutase, catalase and glutathione peroxidase were seen to
      decrease following aluminum exposure. A significant decrease in the nonprotein
      sulfhydryl (NPSH) group status was also observed along with a decreased
      NPSH:disulfide ratio, thus further accentuating the oxidative insult to tissue.
      In vitro addition of desferrioxamine was shown to reverse aluminum induced lipid
      peroxidation, suggesting the probable therapeutic role of the drug against
      aluminum neurotoxicity.

PMID- 8875706
TI  - Small round cell tumors of bone and soft tissue. Introduction.

PMID- 8875707
TI  - Histology, immunohistochemistry, and electron microscopy of small round cell
      tumors of bone.
AB  - Small round cell tumors (SRCTs) of the bone make up a family of primary bone
      sarcomas with morphologically, biologically, and clinically specific features.
      Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties
      such as atypical ES, large cell ES, and ES with neuroectodermal differentiation
      (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of
      the bone) have been identified recently. Histology and electron microscopy
      together with the variable expression of several epitopes (as shown by
      immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for
      characterizing the group within the context of neuroectodermal-derived neoplasms.
      A number of other ES-like tumors with small round cells, mimicking those
      previously described, have been characterized; Askin's tumor of the
      thoracopulmonary region will be considered as an ES similar to those already
      described, but within a particularly anatomic location. On the other hand, the
      presence of an endothelial appearance within a poorly differentiated neoplasm may
      be present in some ES-like SRCTs (atypical ES with endothelial features). The
      differential diagnosis with other sarcomas defined by small round to spindle cell
      contours might prove difficult. Particular attention must be paid to small cell
      osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of
      bone" is considered in this study because it is a very rare neoplasm differing
      from the formerly discussed types; its pluripotentiality provides this tumor a
      blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's
      lymphoma is an unusual presentation when primary to the bone, previous to any
      other anatomic location. Several subtypes have been considered within a histology
      that encompasses that seen in lymph nodes.

PMID- 8875708
TI  - Cytogenetics and tissue culture of small round cell tumors of bone and soft
      tissue.
AB  - The variety of tumor-specific cytogenetic and genetic alterations among small
      round cell tumors (Ewing family of tumors, rhabdomyosarcoma, neuroblastoma, and
      lymphoma) increases the possibility of genotypic diagnosis of them. In Ewing's
      sarcoma and related peripheral primitive neuroectodermal tumors, a
      (11;22)(q24;q12) translocation is associated with hybrid transcripts of the EWS
      gene with the FLIl gene. In alveolar rhabdomyosarcoma, a (2;13)(q35;qt4)
      translocation is associated with a chimeric gene between PAX3 and FKHR. Specific
      genetic alterations of the short arm of chromosome 1 and amplification of the
      MYCN gene are diagnostically useful in neuroblastomas as the immunoglobulin or T
      cell receptor gene rearrangements and chromosome translocations in lymphomas.
      Thus, cytogenetics and genetics provide an essential adjunct to diagnostic
      surgical pathology in the case of small round cell tumors, which often present
      substantial diagnostic challenges. Likewise, in vitro culture studies represent
      another approach in determining histogenetic origin, novel genes, novel
      mechanisms of gene dysregulation, and the biological characteristics of small
      round cell tumors.

PMID- 8875709
TI  - Soft tissue small round cell tumors: morphological parameters.
AB  - Soft tissue small round cell tumors (SRCTs) comprise a heterogeneous group of
      neoplasms that predominate in childhood and adolescence and share similar
      morphological features, consisting of dense cellular proliferation of small round
      cells with a primitive appearance. Rhabdomyosarcomas, peripheral
      neuroepitheliomas, Ewing's sarcomas, and lymphomas/leukemias are the prototypic
      SRCT; other recently described tumors that should be added to the list are the
      desmoplastic SRCT and the rhabdoid tumor of soft tissues. In addition, several
      other primary soft tissue neoplasms and metastatic tumors have occasionally been
      considered in the differential diagnosis of SRCT. The precise identification of a
      given SRCT is important because of its clinical relevance. However, it may be
      difficult because the diagnostic criteria are sometimes subtle and several
      histologic and immunohistochemical features are not specific and/or may be
      simulated by different tumor types. We discuss the morphological clues that in
      our opinion are most useful for their diagnosis, the criteria for distinguishing
      between peripheral neuroepithelioma and Ewing's sarcoma, and the main diagnostic
      pitfalls.

PMID- 8875710
TI  - Desmoplastic small round cell tumor.
AB  - Desmoplastic small round cell tumor is an undifferentiated tumor associated with
      serosal surfaces, especially the peritoneum. It is found predominantly in
      adolescents and young adults and is much more common in males than in females.
      The tumor has a characteristic histology, with extensive stromal tissue around
      islands of small and undifferentiated cells revealing the desmoplastic
      appearance. The coexpression of epithelial and mesenchymal antigens distinguishes
      this entity from other small round and blue cell tumors of this age group.
      Cytogenetic studies showed a t(11;22) translocation that differs from the Ewing's
      tumor translocation and seems to be specific to this entity. The involvement of
      the WT1 and EWS genes in the translocation makes this tumor an interesting
      subject for research on histogenesis and differentiation in small round and blue
      cell tumors.

PMID- 8875711
TI  - Differential diagnosis of small round cell tumors.
AB  - The differential diagnosis of small round cell tumors includes not only the small
      round cell tumors of infancy and childhood, but a variety of mesenchymal,
      cutaneous, and lymphoreticular neoplasms that may occur in adults as well as
      children. Moreover, lesions considered to be the classical small round cell
      tumors of childhood may occasionally occur in adults, and lesions
      characteristically seen in adults may at times occur in children. An awareness of
      the diverse lesions that may present as small round cell tumors is critical to
      arrive at the correct diagnosis. Immunohistochemical techniques and
      ultrastructural studies have now become indispensable in the diagnosis of small
      round cell tumors. With recent developments in cytogenetic and molecular genetic
      techniques, the pathologist has acquired an even more powerful and precise
      armamentarium of diagnostic tools. Judicious use of these methods, with knowledge
      of their significance and limitations, is the responsibility of the pathologist
      and laboratory coworkers who play a pivotal role in patient care and treatment.
      The differential diagnosis of small round cell tumors, including adult-type
      sarcomas, lymphoreticular malignancies, and neuroectodermal tumors of skin and
      viscera that simulate classical small round cell tumors, is briefly reviewed with
      this perspective. Specific cytogenetic and molecular markers are covered in
      addition to the typical immunohistochemical and ultrastructural features of
      several diverse lesions.

PMID- 8875712
TI  - Molecular genetics of small round cell tumors.
AB  - The small round cell tumors of children and young adults constitute part of a
      group of undifferentiated tumors, the precise diagnosis of which is often a
      challenge for the pathologist because of their uniform morphological appearance.
      Diagnostic cytogenetic analysis and identification of specific chromosomal
      abnormalities have been especially useful for the classification of some of these
      tumors. The cloning of the genes and molecular characterization of the associated
      genetic anomalies have led to the discovery of the mechanisms involved in their
      neoplastic transformation and identified a variety of tumor-specific molecular
      genetic markers. Information has also been provided regarding the histogenetic
      origin and mechanisms of differentiation in these tumors. This review focuses on
      the tumor-specific genetic markers, particularly those of clinical relevance, and
      the recently identified genes and deregulation mechanisms associated with them.
      The availability of these markers provides auxiliary methods with increasingly
      improved resolution for primary diagnosis and classification of histologically
      similar tumors and tools for monitoring patients and identifying potential
      antineoplastic therapy targets.

PMID- 8875713
TI  - Small round blue cell tumors in bone: prognostic factors correlated to Ewing's
      sarcoma and neuroectodermal tumors.
AB  - Ewing's sarcoma and peripheral neuroectodermal tumors are the most common small
      round blue cell tumors of bone. Accurate prognostic factors are required to
      define guidelines to standardize the treatment modalities and to adapt these
      modalities to the potential evolution of the disease. The various factors that
      have emerged in the literature as influences on the outcome of patients with
      Ewing's sarcoma or peripheral neuroectodermal tumors of bone are considered in
      this review. The presence of metastases at the clinical onset of the disease
      represents the most adverse prognostic factor. For nonmetastatic patients, axial
      location appears to be the most unfavorable factor, despite initial tumor volume,
      by showing that the tumor burden could be a more appropriate indicator of patient
      outcome. The importance of a local control of the disease by surgery has been
      emphasized, and the value of the histopathologic evaluation of the response to
      chemotherapy has been stressed.

PMID- 8875714
TI  - Sensory innervation to the anterior portion of lumbar intervertebral disc.
AB  - STUDY DESIGN: The level of dorsal root ganglia that receives sensory afferent
      nerves from the anterior portion of the lower lumbar intervertebral disc was
      investigated in rats using a retrograde transport method. OBJECTIVES: Sometimes
      patients with lower lumbar disc lesions complain of inguinal pain that does not
      correspond to the dermatome of the injured nerve roots. To investigate the origin
      of the pain, the authors studied the sensory innervation to the anterior portion
      of the lumbar intervertebral disc. SUMMARY OF BACKGROUND DATA: The innervation to
      the posterior portion of the lumbar disc has been extensively investigated and
      has been reported to be segmental. However, little is known about the nerve
      supply to the anterior portion of the lumbar disc. METHODS: The retrograde
      transport method was used in rats. As tracers, horseradish peroxidase and
      choleratoxin B subunit were used. Horseradish peroxidase crystals were placed on
      the anterior portion of the L5-L6 disc, and choleratoxin B subunit was injected
      into the L5-L6 disc. The bilateral dorsal root ganglia were histologically
      examined. RESULTS: Labeling of L1 and L2 dorsal root ganglia neurons was
      recognized. No neurons were labeled in dorsal root ganglia of other levels,
      including the segmentally corresponding L5. CONCLUSIONS: Using the retrograde
      transport method, the authors demonstrated that the anterior portion of the L5-L6
      lumbar intervertebral disc was innervated from L1 or L2 spinal nerves in rats.
      These results appear to explain the reason why patients with lower lumbar disc
      lesions sometimes complain of inguinal pain corresponding to the L1-L2 dermatome.

PMID- 8875715
TI  - Vulnerability of great medullary artery.
AB  - STUDY DESIGN: The present study describes anatomic observations on great
      medullary artery and intercostal arteries pertinent to thoracolumbar spinal
      surgery. OBJECTIVES: This study reveals the vulnerable course of the great
      medullary artery and its relationship to the lateral or posterolateral approach
      to thoracic spine. SUMMARY OF BACKGROUND DATA: There are no previous anatomic
      data on the length of the great medullary artery, its intradural course, its
      relationship with the anterior spinal artery, and the distance between two
      adjacent intercostal arteries. METHODS: The location of the intercostal arteries
      was defined, and the distance between two adjacent arteries was measured at a
      point on the lateral surface of the vertebra midway between its anteroposterior
      diameter. The intradural length of the great medullary artery and the angle it
      formed with the anterior spinal artery at the point of anastomosis were also
      measured. RESULTS: The mean intradural length of the great medullary artery was
      3.6 cm (range, 1.7-8.1 cm), and it passed over 1-3 disc spaces before joining the
      anterior spinal artery at a mean angle of 20.1 degrees (range, 12-28 degrees).
      The average distance between two adjacent intercostal arteries from T6 to L2 was
      3.6 cm (range, 2.8-4.0 cm), which provides a safe window through which a
      herniated thoracic disc may be approached if surgery is indicated. CONCLUSIONS:
      The acute angle between the great medullary artery and anterior spinal artery
      indicates that these two arteries are in close proximity for considerable length
      and are liable to be compressed together with the intervening vascular
      collaterals by a space-occupying lesion, such as disc herniation or a fractured
      fragment. The longer the intradural course of the great medullary artery, the
      more vulnerable it is to compression by disc herniation or fracture. The
      intercostal and lumbar arteries are located at the midportion of the lateral
      aspect of the vertebral bodies rather than at the level of intervertebral discs.
      Discectomy or decompression of the anterior thoracic canal may be accomplished
      through a lateral or posterolateral extracavitary approach between two
      intercostal or lumbar arteries.

PMID- 8875716
TI  - Prevalence, morphology, and topography of blood vessels in herniated disc tissue.
      A comparative immunocytochemical study.
AB  - STUDY DESIGN: Ninety disc herniations removed during surgery were studied by
      immunocytochemistry, using two different endothelial cell markers, to study the
      prevalence, morphology, and topography of blood vessels in disc herniations.
      OBJECTIVES: To increase the specific localization of even very small blood
      vessels present in disc herniations by using specific antibodies to endothelial
      cells; to study blood vessels comparatively with two different endothelial cell
      antibodies, comparing their prevalence; and to study blood vessel morphology and
      topographic relationships of blood vessels to other tissue elements, particularly
      disc cells. SUMMARY OF BACKGROUND DATA: In many previous macroscopic studies and
      in studies using conventional histologic methodology, blood vessels have been
      observed in degenerated and injured intervertebral discs. In a smaller patient
      sample, the authors previously observed blood vessels in approximately 80% of
      disc herniations by immunocytochemistry, the blood vessels co-localizing with
      macrophage cells. Many of these blood vessels are the product of very active
      neovascularization after disc tissue injury. The presence of such blood vessels
      has not, however, been studied in greater detail or in larger patient samples.
      Immunocytochemistry offers superior visualization and more specific localization
      and was thus used in the present study. METHODS: Thin frozen sections from 90
      disc herniations were immunostained in parallel with von Willebrand factor and
      Ulex europaeus antibodies, both of which localize endothelial cells specifically.
      Indirect immunocytochemistry by avidin-biotin-peroxidase complex or alkaline
      phosphatase-antialkaline phosphatase were used for immunolocalization. Blood
      vessels were classified as being: +, abundant: (+), very few; or +, totally
      absent. RESULTS: The prevalence of blood vessels in disc herniations was found in
      82 of 90 (91%) disc herniations with von Willebrand factor antibody and in 75 of
      90 (83%) disc herniations with Ulex europaeus antibody. In 59 disc herniations
      (66%), blood vessels were observed with both antibodies in parallel, whereas they
      were observed with neither antibody in only six of 90 disc herniations.
      Furthermore, the ratio of abundant to very few blood vessels was 73:9 with von
      Willebrand factor antibody and 63:12 with Ulex europaeus antibody, further
      supporting the abundance of blood vessels in disc herniations. Blood vessels were
      most prevalent in sequestrated discs, but they were also observed in six of eight
      protrusions. Dense blood vessel networks were observed to penetrate the disc
      tissue, and blood vessels were also present in areas of inflammatory cell
      infiltration. Topographically, blood vessels were, on several occasions and with
      both antibodies, seen to pass close by or to surround disc cells. CONCLUSIONS: By
      immunocytochemistry with endothelial cell markers, blood vessels can be observed
      to be numerous, and their prevalence in herniated discs is very high, presumably
      as a result of a very intense neovascularization process after the disc injury. A
      close apposition to disc cells may suggest attempts to increase the nutrition of
      these cells and will influence the metabolism of the cells.

PMID- 8875717
TI  - Immunocytochemical localization of immunoglobulins in disc herniations.
AB  - STUDY DESIGN: Disc herniation and control discs were studied for the presence of
      immunoglobulins immunocytochemically. OBJECTIVES: To study a possible presence of
      immunoglobulin complexes in herniated disc tissue and to locate them at the
      tissue level by immunocytochemistry; to compare immunohistologic findings with
      those obtained in control disc tissue; and to compare the prevalences of
      immunoglobulin M and immunoglobulin G. SUMMARY OF BACKGROUND DATA: In herniated
      disc tissue, high activity of inflammatory phospholipase A2 was previously
      demonstrated, and inflammatory cells were noted immunohistochemically.
      Immunoglobulins G and M were observed biochemically but have not been located at
      the tissue level. METHODS: Fifty-two disc herniations and three macroscopically
      normal fresh cadaver discs were managed by an identical immunocytochemical
      protocol, using monoclonal antihuman antibodies to immunoglobulins M and G.
      RESULTS: In 29 of 52 disc herniations (56%), immunoglobulin M deposits were
      observed, and in 18 of 52 disc herniations (35%) immunoglobulin G could be
      demonstrated. Almost all the disc herniations where immunoglobulin G was present
      also contained immunoglobulin M deposits (except for two). In the control discs
      studied, neither immunoglobulin could be observed immunohistochemically. The
      immunoglobulin deposits were noted in areas where blood vessels were also
      present. Morphologically, immunoglobulin immunoreactivity resembling immune
      complexes was observed. CONCLUSIONS: The results lend support to previous
      suggestions of inflammation and immune reaction in disc herniations, including
      previous biochemical studies suggesting immunoglobulin deposition. The exact role
      of the demonstrated immunoglobulins in disc tissue pathophysiology will have to
      be clarified further.

PMID- 8875718
TI  - The effects of nonsteroidal anti-inflammatory drugs on posterior spinal fusions
      in the rat.
AB  - STUDY DESIGN: This was a prospective study to determine the potential effects of
      indomethacin on spinal fusions in the rat. OBJECTIVES: To determine if
      indomethacin exerts a deleterious effect on spinal fusions in the rat model.
      SUMMARY OF BACKGROUND DATA: Nonsteroidal anti-inflammatory drugs are a class of
      compound that affect bone osteogenesis during fracture healing and heterotopic
      ossification. Spinal fusion is a process that occurs via osteogenesis and,
      therefore, may be similarly affected. METHODS: Thirty-nine adult, Sprague-Dawley
      rats underwent a three-level posterior spinal fusion. Fusion was performed using
      morselized autogenous vertebral bone graft obtained via caudectomy and stabilized
      using a cerclage wiring technique. The 39 rats were divided into two groups
      consisting of 17 study animals and 22 control animals. The control group was
      injected with 1.5 cc of 0.9 normal saline subcutaneously for 12 weeks, whereas
      the test animals were injected on an identical schedule using 3 mg/kg of
      indomethacin sodium salt. Two control animals died, and three animals in the
      treatment group died of drug-related complications. Twelve weeks after surgery,
      all animals were killed, and the involved spinal segments were evaluated by
      direct manual examination. A fusion was probable if the spinal segments exhibited
      decreased scaled micromotion. RESULTS: Sixty segmental levels in 20 control
      animals were assessed. Overall, 27 of 60 levels (45%) achieved fusion. In the
      indomethacin-treated group, 42 levels in 14 animals were evaluated. Overall, four
      of 42 levels (10%) achieved a fusion. Chi-square analysis demonstrated a
      significant difference (P < 0.001) between the control and indomethacin-treated
      groups. CONCLUSIONS: This study raises serious questions about the inhibitory
      effects of nonsteroidal anti-inflammatory drugs on spinal fusion. Clinically, the
      widespread use of nonsteroidal anti-inflammatory drugs in the postoperative
      period after spinal fusion may need to be avoided.

PMID- 8875719
TI  - Nonoperative management of herniated cervical intervertebral disc with
      radiculopathy.
AB  - STUDY DESIGN: A longitudinal cohort study design was used. All patients underwent
      a systematically and uniformly applied treatment program with increasing
      intervention as further pain control was needed. All patients were followed up by
      questionnaire evaluating function and symptoms. OBJECTIVES: The role of surgical
      versus nonsurgical treatment of patients with cervical disc herniation has not
      been adequately studied. The majority of published data reflects surgical
      outcomes, with little available data regarding the outcome of nonoperatively
      treated patients. Frequently, these patients are treated surgically if they have
      neurologic loss or radiculopathy that persists after rest or minimal
      intervention. In the authors' clinic, patients with cervical herniated nucleus
      pulposus and radiculopathy are treated with an aggressive physical rehabilitation
      program. SUMMARY OF BACKGROUND DATA: All patients treated by the authors during a
      specified time period with a clearly defined diagnosis of cervical herniated
      nucleus pulposus were evaluated for outcome. METHODS: Twenty-six consecutive
      patients with cervical herniated nucleus pulposus and radiculopathy were
      evaluated by an investigator other than the treating physician. The follow-up
      time was more than 1 year in all patients. Data analyzed included symptom level,
      activity and function level, medication and ongoing medical care, job status, and
      satisfaction. Inclusion criteria included a focal cervical disc protrusion of
      less than 4 mm identified on magnetic resonance imaging and a major complaint of
      extremity pain compatible with cervical radiculopathy. Exclusion criteria
      included severe central canal stenosis, symptomatic cervical myelopathy, or
      condition that precluded participation in the rehabilitation program. Management
      consisted of traction, specific physical therapeutic exercise, oral anti
      inflammatory medication, and patient education. The majority of patients
      presented with neurologic loss. RESULTS: Twenty-four patients were successfully
      treated without surgery. Twenty patients achieved a good or excellent outcome of
      these 19 had disc extrusions. Two patients underwent cervical spine surgery.
      Twenty-one patients returned to the same job. One patient retired. CONCLUSION:
      Many cervical disc herniations can be successfully managed with aggressive
      nonsurgical treatment (24 of 26 in the present study). Progressive neurologic
      loss did not occur in any patient, and most patients were able to continue with
      their preinjury activities with little limitation. High patient satisfaction with
      nonoperative care was achieved on outcome analysis.

PMID- 8875720
TI  - Convex spinal epiphysiodesis in the management of progressive infantile
      idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective review of patient records with current clinical and
      radiographic assessment. OBJECTIVE: To evaluate the long-term result of anterior
      and posterior convex spinal growth arrest, with or without instrumentation, in
      managing infantile idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: There were
      12 male and 10 female patients studied, with a mean follow-up period of 10 years,
      9 months. The mean Cobb angle before surgery was 65 degrees. All had a rib
      vertebral angle difference more than 20 degrees. The mean age at surgery was 6
      years. Nine patients had epiphysiodesis alone; nine patients also underwent
      Harrington instrumentation simultaneously, and four underwent Harrington
      instrumentation 2-4 years later. METHOD: Clinical evaluation and sequential
      measurements of Cobb angle were done. RESULTS: The epiphysiodesis-only group had
      a mean preoperative Cobb angle of 72 degrees, mean progression of curves of +12
      degrees, and mean rate of progression of +2.5 degrees per year: the group's
      postoperative figures were 92 degrees, +15 degrees, and +3 degrees per year,
      respectively. The epiphysiodesis and late Harrington rod group had a mean
      preoperative Cobb angle of 56 degrees, mean progression of +12 degrees, and a
      mean rate of progression of +5 degrees per year; the group's postoperative Cobb
      angle averaged 62 degrees, progression +6 degrees, and rate of progression +1
      degree per year. The epiphysiodesis with simultaneous Harrington rod group had a
      preoperative mean Cobb angle of 60 degrees, mean progression of +18 degrees, and
      mean rate of progression of +6 degrees per years. After surgery, these improved
      to 58 degrees, correction of 2 degrees, and rate of correction of 0.5 degree per
      year. CONCLUSION: Combined anterior and posterior convex spinal growth arrest
      alone does not prevent progression of deformity in infantile idiopathic
      scoliosis. The addition of posterior instrumentation can slow or arrest deformity
      progression but not reverse it.

PMID- 8875721
TI  - Results of sacroiliac joint double block and value of sacroiliac pain provocation
      tests in 54 patients with low back pain.
AB  - STUDY DESIGN: This prospective study consisted of the evaluation of a double
      sacroiliac block in patients with low back pain. OBJECTIVES: To determine the
      prevalence of sacroiliac pain in a selected population of patients suffering from
      low back pain, and to assess certain pain provocation tests. SUMMARY OF
      BACKGROUND DATA: Previous studies have implicated the sacroliac joint as a
      potential etiology of back and leg pain, but none has tested double anesthetic
      blocks in a prospective fashion. METHODS: Fifty-four patients with unilateral low
      back pain, pain mapping compatible with a sacroiliac origin, tenderness over the
      sacroiliac joint, and no obvious source of pain in the lumbar spine were selected
      for a double anesthetic block. The procedure consisted of a through clinical
      examination with a visual analog scale, testing of sacroiliac pain provocation
      tests followed by a first screening block with a short-acting anesthetic. A
      second examination consisting of the same tests assessed the efficacy of the
      first block. If results were positive, a confirmatory block was performed. All
      blocks were performed under fluoroscopic guidance. RESULTS: Nineteen patients had
      a positive response to the first block. Among them, 10 (18.5%) were temporarily
      relieved by the confirmatory block. No pain provocation test reached statistical
      significance. CONCLUSION: The present study suggests the sacroiliac joint is an
      uncommon but real source of low back pain. The accuracy of some of the presumed
      "sacroiliac pain provocations tests" is questioned.

PMID- 8875722
TI  - Are postoperative activity restrictions necessary after posterior lumbar
      discectomy? A prospective study of outcomes in 50 consecutive cases.
AB  - STUDY DESIGN: A prospective clinical trial was conducted. OBJECTIVES: To
      determine if removing activity restrictions after surgery and encouraging early
      return to work would affect clinical outcomes after lumbar discectomy. SUMMARY OF
      BACKGROUND INFORMATION: Current practice usually recommends several weeks to
      months of restricted activities after lumbar discectomy. No formal studies have
      been done to determine the optimal period of restriction, if any, after surgery.
      METHODS: Fifty consecutive patients undergoing limited open discectomy for
      herniated lumbar intervertebral disc were prospectively treated with no
      restrictions at all after surgery and were urged to return to full activities as
      soon as possible. The patients were followed for a minimum of 2 years. At follow
      up evaluation, an independent examiner evaluated each patient. RESULTS: The mean
      time from surgery to return to work was 1,7 weeks. Eleven of 44 (25%) patients
      returned to work on the next work day. Ninety-seven percent of patients who were
      working before surgery returned to their previous work. Forty-three of 44 (97%)
      patients had returned to full duty by 8 weeks after surgery. At follow-up
      evaluation (3.8 years), five patients had changed work; three patients increased
      their work level, and two decreased their work level. No patient changed
      employment because of back or leg pain. There were three reherniations at the
      operative level (6%), all occurring more than 1 year after surgery. One patient
      required reoperation. Back and leg pain scores at follow-up evaluation were very
      low. CONCLUSION: Lifting of postoperative restrictions after limited discectomy
      allowed shortened sick leave without increased complications. Postoperative
      precautions in these patients may not be necessary.

PMID- 8875723
TI  - Duration of antituberculosis chemotherapy in conjunction with radical surgery in
      the management of spinal tuberculosis.
AB  - STUDY DESIGN: The effectiveness of duration of antituberculous chemotherapy in
      conjunction with radical surgery for tuberculosis of the spine is reported. One
      hundred fourteen patients were followed prospectively for a mean period of 14.6
      years after radical resection of the tuberculous lesion and reconstruction of the
      resultant gap with bone graft. OBJECTIVE: To evaluate the efficacy of short
      course antituberculous chemotherapy in relation to the standard 18-month
      chemotherapy in conjunction with radical surgery for tuberculosis of the spine.
      SUMMARY OF BACKGROUND DATA: One hundred fourteen patients who were subjects of
      the Medical Research Council's (London, UK) prospective study underwent radical
      resection of the lesion and anterior arthrodesis of the spine. These patients
      received 6, 9, and 18 months of antituberculous chemotherapy. Those who received
      6- and 9-month chemotherapy received streptomycin, rifampicin, and isoniazid.
      Streptomycin was given for the first 3 months, and the other two drugs were
      continued for 6 or 9 months. Those who received 18 months of chemotherapy were
      given streptomycin (first 3 months), sodium para-aminosalicylic acid, and
      isoniazid. METHODS: These patients were followed longitudinally, and at each
      visit, clinical and radiologic data were collected at 1-month intervals up to 3
      months postoperatively, at 3-month intervals to 30 months postoperatively, at 6
      month intervals up to 5 years postoperatively, and at 12-month intervals to the
      conclusion of study (minimum, 10 years). For assessment of spinal deformity, the
      "deformity angle" was measured on lateral spinal radiographs obtained at each
      visit. RESULTS: Six-month, 9-month, and 18-month chemotherapeutic regimens in
      association with radical surgery produced similar clinical results with no
      recurrence or reactivation of tuberculosis. The changes in deformity angles at
      final follow-up evaluation compared with 6-month postoperative values were not
      statistically significantly different in the groups who underwent 6 months, 9
      months, and 18 months of chemotherapy. CONCLUSIONS: The authors' findings show
      that a 6-month chemotherapeutic regimen combined with surgical excision and bone
      grafting is adequate for management of tuberculosis of the spine, as it produced
      clinical and radiologic results comparable with the 18-month chemotherapeutic
      regimen.

PMID- 8875724
TI  - The use of implantable direct current stimulation in multilevel spinal fusion
      without instrumentation. A prospective clinical and radiographic evaluation with
      long-term follow-up.
AB  - STUDY DESIGN: A prospective study with long-term follow-up of 143 patients who
      underwent spinal fusion with direct current stimulation and no instrumentation.
      OBJECTIVES: To assess the effects of direct current stimulation on fusion
      success, clinical outcome, and return to work in multilevel lumbar spinal fusion
      procedures. SUMMARY OF BACKGROUND DATA: Efforts to ensure higher fusion success
      rates in multilevel procedures have resulted in the use of surgical adjuncts,
      such as spinal instrumentation systems and electrical stimulation. METHODS:
      Patients were assessed 3, 6, 12, 18, and 24 or more months after surgery (long
      term follow-up). Fusion was determined by anteroposterior and lateral radiographs
      and lateral bending films and was considered successful if there was evidence of
      bony fusion and the absence of motion between the operated vertebrae. Surgical
      technique included either a posterior facet or posterolateral fusion. RESULTS:
      There were no significant differences (P > 0.05) in fusion success between 12
      month results and the long-term results. The median length of the long-term
      follow-up period was 5.0 years (range, 2-9 years) Nineteen patients were lost to
      follow-up; five were unwilling to return for assessment, and one patient died.
      Fusion success among the remaining 118 patients was 91.5%. Two-level procedures
      (90) had a fusion rate of 93%. Three-level procedures (22) had a fusion rate of
      91%. Eighty-five patients (72%) had no pain; 27 patients (23%) had mild pain
      occasionally, and six patients (5%) had some degree of moderate pain. One hundred
      patients (85%) returned to work; 12 (10%) retired; five (4%) were not working
      before the surgery, and one patient (1%) was unable to return to work. There were
      no worker's compensation patients, and there were no major surgical complications
      in this series. CONCLUSIONS: Multilevel fusion in this series with long-term
      follow-up evaluation of direct current stimulated patients without
      instrumentation showed clinical and radiographic success higher than in recent
      studies without instrumentation and comparable with recent studies using
      instrumentation.

PMID- 8875725
TI  - The outcome of posterolateral fusion in highly selected patients with discogenic
      low back pain.
AB  - STUDY DESIGN: A prospective analysis of the clinical outcome of a consecutive
      series of patients treated with posterior lumbar arthrodesis. Preoperative data
      were collected retrospectively by chart review. OBJECTIVES: To measure by
      independent review the clinical outcome of posterolateral intertransverse fusion
      as a treatment for discogenic low back pain in a highly selected group of
      patients. SUMMARY OF BACKGROUND DATA: Although numerous studies have reported on
      the surgical management of degenerative disc disease, they have been difficult to
      interpret because they lack patient-oriented outcome assessment and objective
      pain measurement criteria, independent review, and include patients with
      diagnoses other than degenerative disc disease. METHODS: Between 1991 and
      February 1993 all patients seen by a single surgeon, evaluated with magnetic
      resonance imaging and discography, and treated with posterolateral lumbar fusion
      were reviewed by independent investigation. Outcome was assessed in the areas of
      radiographic fusion, pain, function, and patient satisfaction. RESULTS: Twenty
      three patients (12 women, 11 men; 100% follow-up an average of 47 months after
      surgery [range, 24-84 months]) met the inclusion criteria. Overall, 39% had a
      good or excellent result, 13% fair, and 48% poor. Nine of 10 patients receiving
      worker's compensation had a poor result, four of five patients with radiographic
      pseudarthrosis had a poor result. Statistically significant improvement in the
      visual analogue scale was noted in the good and excellent group (P = 0.0001) and
      the fair group (P = 0.002) with no change in the poor group. Patients out of work
      more than 3 months before surgery tended to have poor results. Overall, 56% of
      patients were extremely satisfied with the result of their surgery. CONCLUSION:
      Posterolateral intertransverse fusion can be used to successfully manage chronic
      discogenic back pain. However, patient selection remains a challenge, and
      successful outcome appears to be limited in the subset of patients receiving
      worker's compensation and those chronically disabled. Prospective and randomized
      study with objective pain criteria, independent review, and patient-oriented
      outcome is recommended.

PMID- 8875726
TI  - Semirigid instrumentation in the management of lumbar spinal conditions combined
      with circumferential fusion. A multicenter study.
AB  - STUDY DESIGN: Patients with the diagnosis of degenerative disc conditions or
      spondylolisthesis undergoing circumferential fusion with posterior pedicle screw
      fixation using a semirigid rod were reviewed. OBJECTIVES: To determine the
      effectiveness of this approach in achieving a spinal fusion and satisfactory
      clinical outcome, and to determine the complications associated with the
      procedure. SUMMARY OF BACKGROUND DATA: The use of instrumentation to stabilize
      the lumbar motion segments and thereby enhance the fusion rate has been proposed
      in a number of studies. Semirigid fixation was believed to be effective in
      achieving these objectives without concern for stress-shielding, which was
      suggested by some authors using rigid fixation systems. METHODS: Patients who
      required spinal fusion with anterior and posterior approaches because of specific
      lumbar pathology or previous surgeries were selected. The surgery consisted of an
      anterior interbody fusion using allograft, followed by a posterolateral fusion
      and pedicle screw fixation. Fusion was determined by continuity of trabecular
      bridging, and outcomes were determined by pain reduction and return to previous
      levels of activity. Fusion was considered solid if the two posterolateral areas
      were fused (Zones one and two), if the anterior interbody area was fused (Zone
      three), or if all three zones were fused. Complications were documented during
      and after surgery. RESULTS: Sixty-two percent of patients had previous surgery
      with 25% of these patients having a diagnosis of pseudarthrosis. Fifty-five
      percent of patients had two or more levels fused, and 43% were heavy smokers.
      Ninety-seven percent of patients had successful fusions. Pain was significantly
      reduced on a pain analogue scale from 7.1 to 2.1 in the back and from 5.8 to 1.5
      in the leg (p < 0.006 and 0.0001, respectively). Fifty-nine percent of patients
      returned to their previous level of activity, and 18% returned to lighter work or
      job retraining, for a total of 77% returning to the same or lighter levels of
      activity. Complications included metal failure, 4.9%; neurologic deficit, 1.2%;
      deep infection, 1.2%; deep venous thrombosis, 4.9%; and vascular injury, 2.4%.
      Fatal pulmonary embolus occurred in one patient. CONCLUSION: This technique
      produces a satisfactory fusion rate (97%) and a good clinical outcome based on
      pain reduction and return to a satisfactory level of activity (77%). It is
      associated with few, but significant, complications that compare well with other
      reported series in a difficult group of patients. This procedure should be
      reserved for patients who are considered to be at high risk for not achieving
      spinal fusion.

PMID- 8875727
TI  - En bloc resections of bone tumors of the thoracolumbar spine. A preliminary
      report on 29 patients.
AB  - STUDY DESIGN: Twenty-nine patients with primary bone tumors and solitary
      metastases of the thoracolumbar spine treated with en bloc resection are reviewed
      retrospectively. OBJECTIVE: To demonstrate the possibility to apply in the spine
      the same principles of surgical oncology adopted for primary bone tumors of the
      limbs. SUMMARY OF BACKGROUND DATA: The surgical oncologic staging systems
      currently applied in limb tumor surgery are difficult to apply to spinal tumors.
      The anatomic conditions make extralesional surgery difficult or impossible, which
      has restrained a more common use of resection surgery in the spine. Focus is put
      on a new surgical staging system and en bloc vertebral resection. METHODS: Twenty
      five primary malignant and aggressive benign bone tumors and four solitary
      metastases were treated. The patients were submitted to oncologic and surgical
      staging for surgical planning. The primary tumors were classified according to
      Enneking system: three Stage IA, six Stage IB, eight Stage IIB, eight Stage 3
      benign. Staging according to the Weinstein-Boriani-Biagini system was also done.
      Thirteen lesions involved the vertebral body; nine lesions developed in the
      posterior arch, or part of it, and seven lesions occupied part of the body and
      part of the arch. A careful anesthesiologic evaluation was performed as well as a
      continuous intraoperative on-line monitoring of the vital parameters. The en bloc
      resections (multisegmental in five patients) were performed in 10 thoracic, in 16
      lumbar, in two thoracolumbar lesions, and in one lumbosacral lesion.
      Reconstruction was performed, aiming to replace the resected columns. The
      specimens were submitted to histologic study of the margins. All the patients
      were followed, and their status was defined on clinical and imaging studies.
      RESULTS: In 20 patients, a wide margin was achieved, in eight a marginal margin,
      in one an intralesional margin. The margin was contaminated in seven patients.
      Surgical time was 3-21 hours (average, 12 hours). No patient died during surgery
      or from surgical complications. Three mechanical failures of the implants
      required additional surgery. One deep infection arose. The only neurologic
      problems observed were related to the nerve roots sectioned for oncologic
      purpose. No local recurrence was found at follow-up evaluation after 6-134 months
      (average, 30 months). CONCLUSIONS: En bloc resection can be performed in selected
      tumors of the spine; the indication to such major surgery must be based on the
      oncologic stage, and the procedure must be carefully planned. For this purpose,
      the Weinstein-Boriani-Biagini system could be a helpful tool. Long-term results
      must be weighed before a definitive statement of the indications can be made.

PMID- 8875728
TI  - Quadriplegia after lumbar disc surgery. A case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a case of quadriplegia after
      surgery in the prone position for a herniated lumbar disc. SUMMARY OF BACKGROUND
      DATA: Ischemia in the vascular territories of the vertebral arteries after back
      surgery in the prone position is rare. Degenerative changes of the cervical spine
      or decreased blood flow to the head with mechanical vessel obstruction during
      extreme neck movements, systemic hypotension, and thromboembolism have mostly
      been implicated in the pathogenesis. METHODS: The case of a 33-year-old man
      undergoing surgery for an unilateral single level disc herniation at L4-L5 is
      presented. Within a few hours after surgery he developed quadriplegia and signs
      of occipital lobe dysfunction. He underwent magnetic resonance imaging
      investigation. Therapy included arterial blood pressure control, low molecular
      dextran, dexamethasone, bladder catheterization, and physiotherapy. RESULTS:
      Magnetic resonance imaging demonstrated intramedullary ischemic changes in the
      cervical spinal cord and at the borderline between anterior and posterior
      circulation. Outcome after 2 years is fair regarding the severe initial deficit
      the patient walks alone with a cane and bladder function is under control. He is
      employed in a sedentary job. CONCLUSIONS: The authors believe that a temporary
      mechanical occlusion of a vertebral artery led to stasis, formation of thrombi,
      and subsequent embolism in the vertebrobasilar vascular territory. Extreme head
      rotation and neck extension is to be avoided in the prone position.

PMID- 8875729
TI  - Warfarin-induced spondyloarthropathy with pseudotumor-like appearance. A case
      report.
AB  - STUDY DESIGN: This case report illustrates an unusual complication of chronic
      warfarin administration. OBJECTIVES: The presurgical determination that the
      destructive process at L1-L2 was not infection or neoplasm involved the
      recognition that there was instability at this level resulting from chronic
      stress fractures. SUMMARY OF BACKGROUND DATA: Periosteal or osseous hemorrhagic
      masses (pseudotumors) have been well described in patients with hemophilia. To
      the authors' knowledge, this is the first reported case of this well-known
      phenomenon occurring in the axial skeleton as a consequence of warfarin
      administration. METHODS: Serial radiographic studies of the lumbar spine were
      available showing a progressive destructive lesion at L1-L2 and coinciding with
      the initiation of warfarin anticoagulation after aortic valve replacement.
      RESULTS: The destructive mass was demonstrated surgically to represent a large
      partially solidified chronic hematoma. CONCLUSIONS: Patients with stress
      fractures of the posterior arch and subsequent instability may be subject to
      development of such a spondyloarthropathy. Recognition of this unusual potential
      complication of warfarin therapy would prevent an incorrect diagnosis of tumor or
      infection. Early recognition of its occurrence could lead to early spinal
      stabilization.

PMID- 8875730
TI  - Minnesota Multiphasic Personality Inventory (MMPI)

PMID- 8875731
TI  - Why did maternal mortality decline in Matlab?
AB  - In 1991, an article on the Maternity Care Program in Matlab, Bangladesh, reported
      a substantial decline in direct obstetric deaths in the intervention area, but
      not in the control area. The decline was attributed primarily to the posting of
      midwives at the village level. In this article, data are presented from the same
      period and area on a variety of intermediate events. They indicate that the
      decline in deaths was probably due to the combined efforts of community midwives
      and the physicians at the Matlab maternity clinic. Their ability to refer
      patients to higher levels of care was important. The data further indicate that
      the decline in deaths depended upon the functioning of the government hospital in
      Chandpur, where cesarean sections and blood transfusions were available. Midwives
      might also have made a special contribution by providing early termination of
      pregnancy, which is legal in Bangladesh.

PMID- 8875732
TI  - Evaluating the program effects of a radio drama about AIDS in Zambia.
AB  - This study describes an approach to the analysis of data that is designed to
      isolate program effects for evaluations and applies that approach to a program in
      Zambia designed to disseminate AIDS information. Evidence is considered that a
      radio drama broadcast for nine months had an impact on knowledge and behavior
      related to AIDS among Bemba speakers in northern Zambia. Using results from large
      sample surveys (1,600 men and women), conducted before and after the drama was
      broadcast, the analyses compare changes in knowledge and behavior in those most
      likely and least likely to have listened to the broadcast. While the population
      as a whole had improved its knowledge substantially, and some people reported
      having reduced risky behavior, attributing these changes to the program itself
      was not possible.

PMID- 8875733
TI  - The long-term demographic role of community-based family planning in rural
      Bangladesh.
AB  - Experimental studies demonstrating the effectiveness of nonclinical distribution
      of contraceptives are typically conducted in settings where contraceptive use is
      low and unmet need is extensive. Determining the long-term role of active
      outreach programs after initial demand is met represents an increasingly
      important policy issue in Asia, where contraceptive prevalence is high and fixed
      service points are conveniently available. This article examines the long-term
      rationale for household family planning in Bangladesh-where growing use of
      contraceptives, rapid fertility decline, and normative change in reproductive
      preferences are in progress, bringing into question the rationale for large-scale
      deployment of paid outreach workers. Longitudinal data are analyzed that record
      outreach encounters and contraceptive use dynamics in a large rural population.
      Findings demonstrate that outreach has a continuing impact on program
      effectiveness, even after a decade of household visitation. The policy
      implications of this finding are reviewed.

PMID- 8875734
TI  - Confidence intervals and sample-size calculations for the sisterhood method of
      estimating maternal mortality.
AB  - The sisterhood method is an indirect method of estimating maternal mortality that
      has, in comparison with conventional direct methods, the dual advantages of ease
      of use in the field and smaller sample-size requirements. This report describes
      how to calculate a standard error to quantify the sampling variability for this
      method. This standard error can be used to construct confidence intervals and
      statistical tests and to plan the size of a sample survey that employs the
      sisterhood method. Statistical assumptions are discussed, particularly in
      relation to the effective sample size and to effects of extrabinomial variation.
      In a worked example of data from urban Pakistan, a maternal mortality ratio of
      153 (95 percent confidence interval between 96 and 212) deaths per 100,000 live
      births is estimated.

PMID- 8875735
TI  - More evils of CYP.

PMID- 8875736
TI  - Haiti 1994-95: results from the Demographic and Health Survey.

PMID- 8875737
TI  - Evaluation of oral exposure to Polnoks R for female rats in developmental
      toxicity studies.
AB  - This study was performed to evaluate the effects of prenatal development of rats
      exposed to Polnoks R, an antioxidant in elastomer processing. Pregnant female
      rats were exposed to Polnoks R by gavage every day on days 6-15 of gestation at
      doses of 170, 340, and 670 mg/kg body weight (b,w) (6%, 13%, and 25% LD50).
      Clinical observations, maternal body weights, and food and water consumption were
      recorded throughout gestation. At scheduled necropsy on 20 day of gestation
      maternal animals were evaluated for body weight, liver, spleen, ovarjan kidney,
      and adrenal weights, number of ovarian corpora lutea, and status of uterine
      implantation sites. Fetuses were counted, weighed, and examined for external,
      skeletal, and visceral alterations. Maternal weight gain was reduced in the group
      receiving Polnoks R at the 670 mg/ kg dose. In all groups the daily food and
      water consumptions were similar to controls. The relative weights of the
      adrenals, ovaries, spleen, and liver of the females intoxicated with the highest
      dose of Polnoks R were significantly higher than control organs. Polnoks R is an
      embryotoxic and fetotoxic agent. It produced a significant increase in the
      average number of postimplantation losses and a decrease in both the weight and
      body length of the fetuses from the pregnant female rats exposed to the highest
      dose. This chemical also produced birth defects-absent or short tail, cleft
      palate, and internal hydrocephalus-but only at doses toxic to the mother.

PMID- 8875738
TI  - Induction of chromosomal aberrations by 2,4-dichloro-6-aminophenol in cultured
      V79 cells.
AB  - 2,4-Dichloro-6-aminophenol (DCAP) is a major metabolite of the herbicide 2,4
      dichloro-6-nitrophenol ammonium (DCNPA). In our previous studies this metabolite,
      but not the parent compound, was found to induce sister chromatid exchanges
      (SCEs) and micronucleus (MN) formation in Chinese hamster lung fibroblasts (V79
      cells). Further studies were carried out to determine whether DCAP can also
      induce structural chromosomal aberrations (CAs) in cultured V79 cells. The assay
      was performed under three different treatment conditions: 1) 3 h treatment
      followed by 17 h post-treatment incubation. 2) 12 h treatment, and 3) 20 h
      treatment with multiple sampling times. Results showed that CAs were induced by
      DCAP in V79 cells. The aberrations were mainly chromatid types (gaps, breaks, and
      deletions), triradials, quadriradials, and complex rearrangements. However,
      induction of CAs appears to be dependent on the treatment condition. The 3 h
      treatment following a 17 h post-treatment incubation gave rise to 24% aberrant
      cells (excluding gaps) and a total of 44 aberrations per 100 metaphases, while
      the 12 h treatment only gave a borderline response and the 20 h treatment did not
      yield a significant increase of CAs at any concentration tested. It seems that a
      short-term treatment with higher concentrations is a better treatment protocol
      for genotoxicity studies of certain cytotoxic chemicals such as DCAP. Results of
      this study further indicate that the herbicide DCNPA is potentially hazardous to
      the exposed population.

PMID- 8875739
TI  - Postnatal effect of arecoline on chlorophyllin-modulated hepatic
      biotransformation system enzymes in suckling neonate and lactating mice.
AB  - The present study evaluates the potential of arecoline alkaloid on chlorophyllin
      (CHL) modulated levels of hepatic biotransformation system enzymes in suckling
      neonate and lactating mice. CHL [50, 100, or 200 mg/kg body weight (b.w.)/day]
      induced significant increases in the hepatic levels of glutathione S-transferase
      (GST) and sulfhydryl (-SH) in lactating dams and suckling pups of 14 or 21 days.
      The depleted level of hepatic Cytochrome (Cyt.) P-450 was observed only in
      lactating dams given 200 mg/kg b.w. CHL. Arecoline (20 mg/kg b.w.) could depress
      the CHL-induced levels of hepatic GST and -SH, while Cyt. P-450 and Cyt. b5
      levels remained unaltered by arecoline alone or arecoline plus CHL treatment. In
      lactating dams the modulated levels of hepatic biotransformation system enzymes
      potentially could affect the detoxication efficacy of administered chemicals
      besides influencing the rate and extent of passage of metabolites to suckling
      neonate.

PMID- 8875740
TI  - Teratogenic effects of sodium valproate in mice and rats at midgestation and at
      term.
AB  - This experiment was carried out with the aims of comparing the embryotoxic
      potential of valproic acid (VPA) in rats and mice, better defining the
      malformation pattern in these species, and comparing the embryotoxic effects
      detectable in mid-pregnancy to those observed in fetuses at term. Pregnant CD:Crl
      rats were treated subcutaneously (s.c.) at 08:00, 16:00, and 00:00 on day 9 of
      gestation with 0, 150, or 300 mg/ kg VPA; pregnant NMRI mice were treated s.c. at
      00:00 on day 7 of gestation, and at 08:00 and 16:00 on day 8 of gestation with
      0,75, 150, or 300 mg/kg VPA. Groups of females were killed on day 9 (mice) or day
      11 (rats) of pregnancy and their embryos were carefully examined under a
      dissecting microscope. The remaining females were killed 1 day before parturition
      and their fetuses were examined for external, visceral, and skeletal
      malformations. A very high frequency (84%) of malformed embryos was recorded in
      the group of mice treated with 300 mg/kg, including open brain folds (73%),
      somite defects (36%), and heart malformations (20%). The rat embryos were less
      sensitive: only 43% of them were malformed after treatment with 300 mg/ kg,
      however, the pattern of malformations was quite similar to that observed in mice.
      The treatment with 150 mg/kg produced about 32% malformed embryos in mice and
      only 8.5% in rats. More than 84% of mouse fetuses from mothers treated with the
      highest dose showed a severe form of exencephaly. The axial skeleton was also
      severely affected. The postimplantation loss reached 52%. Exencephaly and
      skeletal malformations were also recorded in mouse fetuses from mothers exposed
      to 150 mg/kg. The dose of 75 mg/kg was without effects. Exencephaly was not
      observed in rat fetuses at term. In this species the axial skeleton was the most
      severely affected region at 300 mg/kg, while the lowest dose produced only
      sporadic malformations. These results confirm that the mouse is the more
      sensitive species for the teratogenic effects of VPA. Furthermore, it has been
      shown that, in both species, the axial skeleton is a system which is very
      sensitive to the teratogenic effects of VPA. The observed alterations show a
      possible link between axial specification and VPA and suggest further studies of
      embryos exposed to VPA for the expression of genes controlling the identity of
      vertebral segments.

PMID- 8875741
TI  - Developmental toxicity of carboxylic acids to Xenopus embryos: a quantitative
      structure-activity relationship and computer-automated structure evaluation.
AB  - The developmental toxicity for each of 45 carboxylic acids was determined for
      Xenopus embryos. Acids tested included 12 unbranched, saturated aliphatics, 12
      branched, saturated aliphatics, 12 unsaturated aliphatics, and 9 aromatics.
      Embryos were collected following hormone-induced breeding and exposed to at least
      eight concentrations of the acid, along with a control. For each concentration,
      25 properly developing embryos were exposed to the acid solution for 96 h. Each
      acid was tested on at least three separate occasions and the data were pooled to
      calculate 96-h LC50 (lethality), 96-h EC50 (malformation), and DHI (developmental
      hazard index = 96-h LC50/96-h EC50) values. The endpoint data were subjected to
      quantitative structure-activity relationship (QSAR) analyse: and computer
      automated structure evaluation (CASE). Variation in acid-induced lethality was
      effectively explained by partitioning and ionizability of the acids, while
      partitioning alone was somewhat effective in explaining variation for acid
      induced malformation. The results indicated that developmental hazard of the
      acids to Xenopus embryos is primarily dependent on carbon-chain length, with
      acids containing five carbon atoms in the chain tending to be the most potent.
      Unsaturation reduced the hazard in comparison with the corresponding unbranched
      saturated acid. Developmental hazard was highest for 2-position branched
      compounds with a 5- or 6-C chain, but was reduced for 2-position branched acids
      with a 3- or 4-C chain. Hazard of the non-2 position branched acids was variable.
      Valproic (2-propylpentanoic) acid showed the highest developmental hazard with
      Xenopus, twice that of any other acid tested.

PMID- 8875742
TI  - An investigation of some Turkish herbal medicines in Salmonella typhimurium and
      in the COMET assay in human lymphocytes.
AB  - Medicinal plants play a major role in the life of Turkish people and of late
      medicinal plant usage has increased in many countries. Green plants in general
      contain mutagenic and carcinogenic substances, but there is little information
      about the biological activities of herbal medicine. In the present study,
      therefore, various Turkish medicinal herbs were investigated for their genotoxic
      potential in the Salmonella typhimurium microsomal activation assay and the
      alkaline single cell gel electrophoresis (COMET) assay. Extracts from these
      medicinal herbs and some fractions of these extracts were examined. The species
      investigated were Arctium minus, Ecballium elatterium, Momordica charantia,
      Plantago major, Urtica dioica, Viscum album, Salvia triloba, Euphorbia rigida,
      Stachys lavandulifolia, Acteoside, Abies nordmannia. They are used for various
      immune disorders and are applied either topically or taken orally as a herbal
      tea. Of the 19 samples of the extracts and fractions investigated, none produced
      a positive response in strains TA98 and TA100 with or without metabolic
      activation, but all produced an increase above negative control values in the
      COMET assay. Some extracts were investigated further and produced dose-related
      increases. In the case of Urtica and Euphorbia species, where two fractions from
      these plants were examined, one fraction produced a greater response than the
      other. It is suggested that the lesser response of the fractions might be due to
      less DNA strand-breaking agents in the fractions or they may have antigenotoxic
      properties. The breaks that are detected in the COMET assay could be alkali
      labile AP-sites and intermediates in base- or nucleotide-excision repair and are
      difficult to interpret in terms of hazard for man. Further studies with
      additional genotoxicity assays would be required to make such a prediction.

PMID- 8875743
TI  - Direct determination of free triiodothyronine (T3) in undiluted serum by
      equilibrium dialysis/radioimmunoassay (RIA).
AB  - We have devised a practical, sensitive, and reliable assay for measurement of
      free T3 concentration in serum. The assay employs a convenient and disposable
      plastic equilibrium dialysis cell and a buffer that resembles the in vivo
      biochemical environment (Nelson JC, Tomei RT 1988 Clin Chem 34:1737). A 200
      microliters aliquot of serum was dialyzed against 2.4 mL buffer at 37 degrees C
      for 18 +/- 2 h and T3 was quantified by RIA of about 1.0-mL aliquot of the
      dialysate buffer. The detection threshold of the RIA approximated 2 pg/ml
      permitting accurate measurement of > 200 pg/dL of free T3 directly. Serum
      specimens that contained less free T3 were spiked with 200 ng/dL of non
      radioactive T3 prior to dialysis. Free T3 in the dialysate of these samples was
      divided by total T3 in serum (after spiking) to determine percent free T3. Free
      T3 was calculated by multiplying percent free T3 and serum total T3 (before
      spiking). Free T3 concentration (pg/dL) did not differ appreciably in a serum
      pool when tested both with and without spiking with exogenous T3. The between
      assay coefficient of variation of three specimens tested over an 8-month period
      averaged 20%. Serum free T3 concentration (pg/dL) was [mean +/- SD (n), range, p]
      [293 +/- 12 (39), 154-440] in normal subjects. It was significantly increased
      [742 +/- 87 (13), 525-1700, p < 0.001] in hyperthyroidism and significantly
      decreased in nonthyroidal illness [NTI, 138 +/- 26 (9), 53-320, p < 0.001], cord
      blood serum [124 +/- 7.5 (11), 93-353, p < 0.001], and third trimester of
      pregnancy [214 +/- 26 (8), 93-253, p < 0.02]. Serum free T3 concentration varied
      widely in hypothyroidism 274 +/- 92 (10), 10-923, NS]. CONCLUSIONS: We have
      described a practical method and initial results of direct measurements of free
      T3 concentration in health and disease.

PMID- 8875744
TI  - Multivariate analysis of HLA loci in conjunction with a thyrotropin receptor
      codon 52 polymorphism in conferring risk of Graves' disease.
AB  - Recent reports have suggested that the HLA alleles DRB3*0101 or DQA1*0501 confer
      greater susceptibility to Graves' disease than does the DR3 allele. We have
      reported previously that a non-HLA-linked allele, a polymorphism in codon 52 of
      the human thyrotropin receptor gene, is highly associated with Graves' disease in
      females. To determine which of these four susceptibility alleles confers greater
      independent risk for the development of Graves' disease, we analyzed the alleles
      in 134 North American Caucasian females who have Graves' disease (n = 69) or are
      normal controls (n = 65) in a logistic regression model. While we found each of
      these alleles to be associated with Graves' disease when analyzed independently
      (corrected p < 0.01 for each of 4 alleles tested), only DR3 (p = 0.0001) and the
      thyrotropin receptor polymorphism (p = 0.0060) maintained a statistically
      significant independent association when assessed in conjunction with each of the
      other alleles in a logistic model. We conclude that DR3 confers the greatest
      susceptibility to Graves' disease (odds ratio = 7.6) of the alleles within the
      HLA locus, and that any association between DRB3*0101 or DQA1*0501 and Graves'
      disease may be a result of the tight linkage disequilibrium between these alleles
      and DR3. In addition, we found the non-HLA-linked thyrotropin receptor codon 52
      polymorphism to confer significant independent risk of Graves' disease (odds
      ratio = 9.0). Further, because 6 of 6 individuals who possessed both DR3 and the
      thyrotropin receptor polymorphism had Graves' disease, while no individual in the
      normal control group possessed both alleles, study of a larger population to
      assess the potential synergism between these 2 alleles is warranted.

PMID- 8875745
TI  - Antibody to gp39, the ligand for CD40 significantly inhibits the humoral response
      from Graves' thyroid tissues xenografted into severe combined immunodeficient
      (SCID) mice.
AB  - Experimental evidence suggests that interference with gp39-CD40 interactions may
      have therapeutic potential in prevention of certain autoimmune disorders (i.e.,
      collagen-induced rheumatoid arthritis). The binding between CD40 expressed on
      mature B cells and CD40 ligand (CD40L, gp39) transiently expressed on activated T
      helper cells (Th) further stabilizes the interactions (between Th and B cells)
      and co-ordinates the responses of the interacting cells during antigen
      presentation, and is essential for thymus-dependent humoral immunity. Graves'
      disease is the most common form of hyperthyroidism, in which hyperactivity of the
      thyroid gland is due to an autoantibody directed against the thyrotropin receptor
      (TSHR). The main objective of our study was to determine the role of interactions
      between gp39 and CD40 in "an established" human Graves' disease (GD). Severe
      combined immunodeficient (SCID) mouse served as a vehicle for human Graves'
      thyroid tissue. This experimental setting allows us to study, observe, and
      immunomodulate human autoimmune tissue in so called in vivo condition. We studied
      the effects of ip administration of anti-gp39 mAb on humoral response, thyroid
      function tests, expression of adhesion molecules, and HLA-DR on human thyrocytes
      and histopathological changes from human GD thyroid tissue xenografts. GD thyroid
      tissue from 4 patients was xenografted into 20 SCID mice (0.8 g/mouse). Human
      immunoglobulin G (IgG) levels became detectable in SCID mice 1 week after
      xenograftment. Ten SCID mice were sequentially administered anti-gp39 mAb (250
      micrograms/mouse/ dose) ip every 4 days until the end of the experiment. Ten
      control animals were injected with vehicle (PBS) in similar fashion. Blood
      samples were taken every 2 weeks from the tail veins for measurement of the
      humoral response [human IgG, thyroid-stimulating antibody (TSAb),
      antithyroperoxidase (anti-TPO), and antithyroglobulin (anti-Tg), Abs], and
      thyroid function tests. After 8 weeks, animals were sacrificed and thyroid tissue
      was examined histologically. The humoral response from the intrathyroidal
      lymphocytes was measured and the tissue morphology of GD was preserved during the
      8-week period in phosphate-buffered saline (PBS)-treated SCID mice xenografted
      with GD xenografts. However, administration of anti-gp39 mAb completely blocked
      or significantly decreased the humoral response in all treated animals. On the
      other hand, no significant histological changes were associated with the
      administration of anti-gp39 mAb. The degree of lymphocytic infiltration in
      thyroid tissue xenografts was comparable in both groups. Serum thyroxine values
      were normal in both groups. In spite of a profound immunosuppressive effect on
      the humoral response by directly blocking CD40-gp39 interactions in vivo, this
      did not result in complete deletion of the responding Th in the thyroid
      specimens.

PMID- 8875746
TI  - Studies of retroorbital tissue xenografts from patients with Graves'
      ophthalmopathy in severe combined immunodeficient (SCID) mice: detection of
      thyroid-stimulating antibody.
AB  - The pathogenesis of Graves' ophthalmopathy (GO) is still unclear and the possible
      role of TSH receptor antibody in the development of GO is controversial. However,
      the recent availability of severe combined immunodeficient (SCID) mice has
      provided a means to study of human autoimmune thyroid disease in an in vivo
      environment. In the present study, we xenografted human retroorbital (RO) tissues
      from 9 patients with GO into 9 SCID mice and the autologous peripheral blood
      mononuclear cells (PBMC) from 5 of 9 GO patients were engrafted into 5 separate
      SCID mice to reconstitute the immunological environment of human GO. Mice blood
      samples were taken every 2 weeks for the measurements of human IgG, thyroglobulin
      antibody (Tg-Ab), thyroperoxidase (TPO)-Ab, thyroid-stimulating antibody (TSAb),
      and interferon-gamma (IFN-gamma). Eight weeks after xenografting, mice were
      killed; RO tissues were analyzed histologically, SCID mice with RO tissues from 2
      of 9 GO patients produced human IgG peaking at 6-8 weeks after xenografting. TPO
      Abs and TG-Abs were detectable in low titer in mice with RO tissue xenografts
      from 3/9 and 4/9 GO patients, respectively. The mean level of IFN-gamma in SCID
      mice with GO RO xenografts was higher than that of a control subject (RO tissue
      from a non-GO patient). TSAbs were actually produced from 7 of 9 mice xenografted
      with GO RO tissues, and reached their peaks at 2-8 weeks after xenografting;
      autologous PBMC (alone, without RO tissues)-engrafted SCID mice did not produce
      any detectable level of TSAb. The control mouse did not produce any detectable
      levels of human IgG, TPO-Ab, Tg-Ab, or TSAb. Immunohistochemical analysis of
      orbital mononuclear cell infiltrates revealed a predominance of T lymphocytes,
      with a small percentage of B lymphocytes in GO RO tissue graft. In conclusion, we
      have successfully reconstituted the SCID mice with human lymphocytes of RO
      tissues from patients with GO. Autoreactive B cell clones responsible for
      secreting TSAb exist in GO RO tissue and may be a key factor in the initiation
      and/or the progression of GO.

PMID- 8875747
TI  - Effects of octreotide treatment on Graves' ophthalmopathy and circulating sICAM-1
      levels.
AB  - Efficacy of octreotide treatment for Graves' ophthalmopathy (GO) and the effects
      of this treatment on the serum levels of the circulating intercellular adhesion
      molecule-1 (sICAM-1) were evaluated. Ten patients with GO were treated with
      octreotide three daily SC injections of 100 micrograms, for 3 months. Octreotide
      treatment was initiated after restoration of euthyroidism with antithyroid drugs.
      All patients were treated with methimazole to maintain euthyroidism during the
      study. Sera were collected from all patients before and 3 months after initiation
      of the study, and from 20 age- and sex-matched healthy subjects for sICAM-1
      measurement. sICAM-1 was measured by a sandwich ELISA method. Proptosis in all
      patients was evaluated by orbital CT scan before and 3 months after initiation of
      the study. Two of 10 patients did not respond to octreotide therapy, while the
      remaining eight patients showed regression or improvement after therapy.
      Octreotide therapy was particularly successful in patients with soft tissue
      involvement of GO (class II or III disease). Mean proptosis and ophthalmopathy
      index scores were significantly decreased after 3 months of octreotide therapy.
      Mean sICAM-1 levels were significantly higher in patients before octreotide
      therapy (470.5 +/- 52.6 ng/mL, p < 0.0001) when compared to normal subjects
      (186.5 +/- 53.3 ng/mL). Mean sICAM-1 levels were significantly decreased 3 months
      after octreotide therapy (from 478.7 +/- 52.6 to 415 +/- 42.8 ng/mL, p = 0.012)
      in the 8 patients who responded to therapy. In contrast, sICAM-1 levels remained
      unchanged or increased in two patients with poor response to octreotide therapy.
      Our results suggest that octreotide therapy could be a treatment modality in
      patients with GO. The mechanism by which octreotide acts on GO is not clear. The
      observed decrease in sICAM-1 levels during octreotide therapy suggests that
      octreotide may have immunomodulatory properties. Further investigation is needed
      to determine the optimal dose and duration of octreotide therapy.

PMID- 8875748
TI  - Sympathetic overactivity of intraocular muscles evaluated by accommodation in
      patients with hyperthyroidism.
AB  - Sympathetic overactivity occurs in Graves' disease, but little is known about
      autonomic nervous function in the eyes of subjects with this disease. We examined
      this function of the intraocular muscles in 12 patients with hyperthyroid Graves'
      disease and 12 healthy controls. Pupil size, pupillary unrest, and accommodation
      were measured with a computer-assisted infrared optometer and pupillometer. The
      mean and the coefficient of variation of the areas of the pupils were used to
      express pupil size and the degree of pupillary unrest, respectively.
      Accommodation was measured with the target light beam moving slowly and steadily,
      or instantaneously, and the results are expressed as the change in the eye's
      refractive power in response to these movements. The mean pupil size of the
      patients was not different from that of the controls. Pupillary unrest in the
      patients was smaller than in the controls. Accommodation in the patients was
      lower than that of the controls. Five patients were examined again 3 months later
      when they became euthyroid; pupillary unrest and accommodation had improved in
      all five patients. There were no significant differences in the activity of
      sympathetic nerves governing intraocular muscles in patients with or without
      eyelid retraction. These results indicate that intraocular muscles are
      sympathetically overactive in patients with hyperthyroidism, and suggest that
      eyelid retraction is not caused by sympathetic overactivity alone, but by another
      factor or factors, in addition.

PMID- 8875749
TI  - Precise determination of TSH receptor antibody activity in serum containing
      bovine TSH (bTSH) binding antibody by absorption using denatured bTSH or sheep
      FSH.
AB  - A previous report demonstrated that sera with bovine TSH (bTSH) binding antibody
      showed abnormally negative TSH receptor antibody (TRAb) activity in the standard
      TRAb assay method. The corrected TRAb activity calculated by the determination of
      the nonspecific binding of the labeled bTSH for each test serum [NSB(T)] resulted
      in positive TRAb activity. However, the precise calculation was difficult because
      NSB(T) level was significantly higher than the nonspecific binding in normal pool
      serum [NSB(N)] level. In the present experiment the determination of the TRAb
      activity was performed after absorption of bTSH binding antibodies by the heat
      denatured bTSH to obtain more precise TRAb activity. In addition, absorption by
      sheep FSH (sFSH) was performed because almost all bTSH binding antibodies showed
      specific binding to the alpha-subunit of mammalian pituitary glycoprotein
      hormones in our previous study. Three days absorption of test serum using 1 mU of
      the heat-denatured bTSH (100 degrees C for 1 h) or 5 mU of sFSH was chosen as
      optimal because NSB(T) decreased remarkably to NSB(N) levels. The corrected TRAb
      determined after these absorptions decreased significantly compared to the
      corrected TRAb activity without the absorption. When the complete absorption of
      bTSH binding antibody was performed by the decrease of the NSB(T) level to the
      NSB(N) level, the TRAb activity determined by these two different absorptions was
      almost similar (difference was less than 10%). However, it was difficult to
      obtain the precise TRAb activity in the cases with extremely high bTSH binding
      antibody, because the NSB(T) level was higher than the NSB(N) level by the
      incomplete absorption of bTSH binding antibody.

PMID- 8875750
TI  - Radioiodine treatment of thyroid carcinoma in patients on maintenance
      hemodialysis.
AB  - To deliver optimal radioiodine activity in hemodialyzed patients with thyroid
      carcinoma, the behavior of radioiodine was followed during six treatments. During
      hemodialysis, blood activity decreases with a half-life of 3.4 +/- 0.5, (1SD) h.
      The whole body dose was calculated from the total activity determined during 10
      days after 131I administration. A reasonable strategy may consist in delivering
      25% of the currently prescribed activity (925 MBq-25 mCi) and to perform the
      first dialysis session after 24 h to reduce total body irradiation.

PMID- 8875751
TI  - Medullary thyroid cancer: analyses of survival and prognostic factors and the
      role of radiation therapy in local control.
AB  - Records of 73 patients with medullary thyroid cancer were reviewed to assess
      prognostic factors and the role of external beam radiation therapy. Patients were
      treated between 1954 and 1992. The median age was 49 years (range 15-85), M:F
      ratio 1.6:1, and the median follow-up was 7.9 years. (2.5-34.6). The primary
      tumor size was < 1 cm in 10%, 1-4 cm in 53%, and > 4 cm in 37%. Multifocality was
      noted in 32%, and 23% had metastasis at presentation. Eight patients presented
      with inoperable tumors, 40% had gross, and 37% microscopic residual disease
      postthyroidectomy. Extraglandular extension was present in 56%, and 74% had
      pathologically involved lymph nodes. Treatment was by total or near total
      thyroidectomy in 41 patients; 37 had a lymph node dissection. Forty-six patients
      were irradiated, the dose of radiation ranging from 20 to 75.5 Gy; median was 40
      Gy, treatment time median was 28 days and the median number of fractions was 20.
      The overall cause specific survival (CSS) was 70% and 57% at 5 and 10 years,
      respectively. In a univariate analysis, the following factors predicted for lower
      CSS: age as a continuous variable (p = 0.003), male gender (p = 0.008), presence
      of distant metastasis (p < 0.0001), lymph node involvement (p = 0.03), gross
      residual disease (p < 0.0001), tumor size > 4 cm (p = 0.05), extraglandular
      invasion (p < 0.004), vascular invasion (p = 0.007), diarrhea (p < .0007), and
      abnormal postoperative calcitonin (p = 0.02). On multivariate analysis only two
      factors were significant: the presence of extraglandular invasion, and
      postoperative gross residual disease. There was no difference in local/regional
      relapse free rate between patients receiving external radiation and those that
      did not, but in 40 high risk patients (microscopic residual disease,
      extraglandular invasion, or lymph node involvement), the local/regional relapse
      free rate was 86% at 10 years with postoperative external beam radiation (25
      patients), and 52% for those with no postoperative external radiation (p =
      0.049). To optimize local/regional tumor control, we therefore continue to advise
      external beam radiation in patients at high risk of local/regional relapse.

PMID- 8875752
TI  - A new mutation in the thyroid hormone receptor (TR) beta gene (V458A) in a family
      with resistance to thyroid hormone (RTH).

PMID- 8875753
TI  - Alterations in TNF-alpha signal transduction in resistant human papillary thyroid
      carcinoma cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) inhibit
      the growth of the human papillary thyroid carcinoma (PTC) cell line, NP. Exposure
      of NP cells to TNF-alpha resulted in the development of several PTC cell lines
      (R30, R45, and R60) with graded loss to the TNF-alpha-induced antiproliferation,
      termed resistance. In contrast, the NP cells and the resistant cells were equally
      sensitive to the antiproliferative action of interferon-gamma. Utilizing TNF
      alpha receptor-specific agonist monoclonal antibodies, we demonstrated that the
      TNF-alpha receptor p55 mediated the antiproliferative action of TNF-alpha, while
      the p75 receptor did not affect cell proliferation in the NP cell line. The
      resistant PTC cell lines, however, showed a graded loss of p55 receptor-mediated
      antiproliferation and a concomitant activation of a p75 receptor-mediated growth
      stimulation. Shedding of TNF receptors is an important mechanism of TNF-alpha
      receptor metabolism. The p55 receptor mediated the TNF-alpha-induced up
      regulation of the shedding of the p75 TNF-alpha receptor. The p75 receptor
      mediated the TNF-alpha-induced down-regulation of the shedding of the p55
      receptor. However, the shedding of the p75 receptor was decreased and the
      shedding of the p55 receptor was increased in the resistant R60 cell line
      compared with the NP cell line, in the presence and absence of TNF-alpha. In
      contrast, IFN-gamma increased shedding of both p55 and p75 TNF-alpha receptors in
      NP and R60 cell lines with equal potency. Furthermore, the resistant PTC cell
      lines have increased basal manganous superoxide dismutase (MnSOD) expression and
      blunted induction of MnSOD mRNA upon short-term. TNF-alpha treatment (less than 2
      h of treatment). The results indicate that a decrease in signal transduction via
      the p55 TNF-alpha receptor and concomitant increase in signal transduction via
      the p75 TNF-alpha receptor are involved in the development of PTC cell
      resistance.

PMID- 8875754
TI  - Effects of iodide on thyroglobulin biosynthesis in FRTL-5 cells.
AB  - Iodide inhibits several thyroid parameters through an organic intermediate, and
      this process has been related to thyroid autoregulation. The aim of this study
      was to determine the effect of iodine on thyroglobulin (Tg) synthesis in the rat
      thyroid cell line FRTL-5. TSH stimulated amino acid incorporation into the cells
      by 400% and iodine had no effect on this parameter. No effect of TSH or iodide on
      [35S] methionine incorporation into protein was found under our experimental
      conditions (approximately 80% of total [35S]methionine incorporated was found in
      TCA-precipitable material). TSH caused an increase in Tg synthesis, after 1 h,
      while iodide partially blocked the effect of TSH (control 6.4% of TCA
      precipitable radioactivity; TSH 10.7%; iodide 8.4%). After 24 h, the protein
      released into the medium was measured. TSH stimulated total protein liberation
      and iodide inhibited this parameter. TSH stimulated total RNA content, and iodide
      caused an inhibition. Northern analysis did not show inhibition by iodide of TSH
      stimulated Tg mRNA levels. The present results show an inhibitory effect of
      excess iodide on TSH-stimulated thyroglobulin biosynthesis in FRTL-5 cells.

PMID- 8875755
TI  - Is there a negative TRE in the luciferase reporter cDNA?
AB  - Transient expression assays using a luciferase (LUC) reporter gene are often used
      in studies of positive and negative thyroid hormone response elements (TREs) or
      of wild-type and mutated thyroid hormone receptors (TRs). However, unliganded TR
      (the beta isoform > than the alpha) increases LUC expression from 2 different TK
      LUC vectors in several cell types, especially JEG-3 cells, and 3,5,3'
      triiodothyronine (T3) reduces that expression by as much as 80% in a TR-dependent
      manner. The TR effects require an intact TR DNA-binding domain and the results
      suggest that there may be a negative TRE in the LUC cDNA. We conclude that great
      care must be used in the interpretation of studies of thyroid hormone action
      using LUC expression plasmids especially when these are performed in JEG-3 cells.

PMID- 8875756
TI  - Long-standing goiter and hypothyroidism: an unusual presentation of a TSH
      secreting adenoma.
AB  - A 63-year-old female patient was referred to our hospital in February 1994 for a
      pituitary tumor. On a previous examination, in 1973, she had a goiter,
      nonspecific symptoms and only an elevated serum T3. In 1984 she had become
      hypothyroid, her goiter had increased, serum T4 was 69 nmol/L, TSH 34.4 mU/L, and
      TPO antibodies were positive. Hypothyroidism due to autoimmune thyroiditis was
      diagnosed and she received L-T4 100 micrograms/day. In 1985 and 1986, serum TSH
      had decreased but remained slightly elevated, while T4 was at the upper limits of
      normal. From 1987 to 1989 her serum TSH rose from 9 to 20 mU/L and remained at
      that level for the ensuing 4 years in spite of increasing L-T4 up to 150
      micrograms/day. In October 1993, after discontinuing L-T4 for 6 weeks, TSH was
      23.7 mU/L, T4 170 nmol/L, 131I thyroid uptake 52%, and the CT scan showed a large
      pituitary tumor with suprasellar extension. On preoperative investigation TSH was
      40-51 mU/L with no response to TRH or GnRH. The alpha-subunit was increased at
      6.33 micrograms/L with the alpha-TSH/TSH molar ratio of 1.23. Prolactin was
      elevated, but plasma cortisol, FSH, and LH were low. At surgery, we found a large
      chromophobe adenoma with few PAS-positive granules and with immunostaining
      positive for TSH and prolactin. From the clinical and biological data, we can
      conclude that the patient had probably a TSH-secreting adenoma since the goiter
      was first detected. The development, however, of autoimmune thyroiditis with
      hypothyroidism considerably modified the presentation of the disease and may have
      accelerated the growth of the tumor.

PMID- 8875757
TI  - Hyperthyroidism caused by an ectopic TSH-secreting pituitary tumor.
AB  - A woman developed what appeared to be typical Graves' disease in 1965 at the age
      of 45 years. After 9 years of antithyroid drug therapy, she was treated with
      radioiodine. Ten years later (1985) she developed postablative hypothyroidism.
      Despite replacement doses of thyroxine that resulted in thyroid hormone levels
      that were in the hyperthyroid range, TSH levels remained elevated. Initial
      biochemical studies, including a high alpha-subunit to TSH ratio, suggested a
      pituitary TSH-secreting tumor, but a CT scan of the sella turcica was normal. In
      1994, while undergoing an otolaryngologic examination, the patient was found to
      have a nasopharyngeal mass lesion, which was ultimately shown histologically and
      immunohistochemically to be an ectopic pituitary tumor. Resection of the mass
      restored TSH and alpha-subunit levels to normal. This patient probably represents
      the first ectopic TSH-secreting pituitary tumor to be reported.

PMID- 8875758
TI  - Graves' disease occurring after subacute thyroiditis: report of a case and review
      of the literature.
AB  - A 57-year-old woman with no previous personal or family history of thyroid
      disease developed typical subacute thyroiditis, with pain and tenderness in the
      anterior cervical region, fever, mild thyrotoxicosis; thyroid autoantibodies were
      negative, serum thyroglobulin (TG) levels were increased, radioactive iodine
      uptake (RAIU) values were decreased, urinary iodine excretion was normal, and
      erythrocyte sedimentation rate (ESR) elevated. Symptoms subsided with
      glucocorticoid treatment, with normalization of serum thyroid hormone and TG
      levels. Four months later, while still on a low dose of glucocorticoid, she had
      recurrence of hyperthyroidism, with no thyroid pain or tenderness, high RAIU
      values, positive thyroid-directed autoantibodies including TSH-receptor antibody.
      HLA typing showed positivity for B35 and DR3, suggesting a genetic susceptibility
      for both subacute thyroiditis and Graves' disease. The development of Graves'
      disease after subacute thyroiditis is extremely rare, suggesting that a genetic
      susceptibility to the disease must exist in such an instance.

PMID- 8875759
TI  - Onset of Graves' thyrotoxicosis after an attack of allergic rhinitis.
AB  - We previously reported that allergic rhinitis was an aggravating factor for
      Graves' disease and that thyrotoxicosis relapsed 2 months after an allergic
      attack. In this paper, we report a patient who showed onset of Graves'
      thyrotoxicosis after an attack of allergic rhinitis. The patient, a 30-year-old
      woman, was initially diagnosed with subclinical autoimmune thyroiditis.
      Interestingly, the patient showed weak activity of thyroid-stimulating antibody
      (TSAb), while TSH-binding inhibitory immunoglobulin (TBII) was negative and her
      thyroid function tests, including TSH, were completely normal. The patient
      developed severe allergic rhinitis in response to Japanese cedar pollen lasting
      from February until April in 1995 with an increase in serum antigen-specific
      immunoglobulin E and peripheral blood eosinophils. Two months later, she
      developed thyrotoxicosis in association with increase in TSAb and TBII. These
      findings suggest that allergic rhinitis not only aggravates Graves' disease but
      also induces the clinical onset of Graves' thyrotoxicosis.

PMID- 8875760
TI  - Serum antibodies reactive with eye muscle antigens and the TSH receptor in a
      euthyroid subject who developed ophthalmopathy and Graves' hyperthyroidism.
AB  - Serum antibodies reactive with eye muscle autoantigens, in particular a 64-kDa
      protein that is also expressed in the thyroid, and the TSH receptor, are
      associated with the ophthalmopathy that occurs in about 50% of patients with
      Graves' hyperthyroidism. We have had the opportunity to study a euthyroid,
      apparently normal, 35-year-old woman with a family history of thyroid
      autoimmunity and "colitis" but no clinical or biochemical evidence for thyroid
      disease or ophthalmopathy, who developed Graves' hyperthyroidism and
      ophthalmopathy together 18 months later. Serum taken when the patient was first
      seen was positive for antibodies reactive with (i) 9 different eye muscle
      proteins ranging in size from 15 to 130 kDa, notably those of 64, 55, and 50 kDa,
      by immunoblotting with eye muscle membranes, (ii) eye muscle and Muller's muscle
      cell membrane antigens in antibody-dependent cell-mediated cytotoxicity (ADCC),
      (iii) an eye muscle cytoplasmic antigen in indirect immunofluorescence, and (iv)
      the TSH receptor as measured in a radioreceptor binding inhibition assay. When
      she developed Graves' disease, serum concentration of antibodies to the 55-kDa
      protein had decreased from +2 to +/-, those reactive with other eye muscle
      antigens had not changed significantly, and TSH receptor antibodies had increased
      3-fold. This case report suggests that antibodies reactive with eye muscle
      antigens and the TSH receptor are markers of the ophthalmopathy and able to
      predict its development in predisposed subjects. The significance of these
      findings needs to be confirmed in a prospective study of first-degree relatives
      of patients with thyroid-associated ophthalmopathy and patients with Graves'
      hyperthyroidism without eye signs.

PMID- 8875761
TI  - Different regulation of thyroid hormone transport in liver and pituitary: its
      possible role in the maintenance of low T3 production during nonthyroidal illness
      and fasting in man.
AB  - Nonthyroidal illness (NTI) and fasting in man are characterized by a low serum
      concentration of T3 and an increased serum concentration of rT3. Since the serum
      level of T3 is one of the most important factors that determine the metabolic
      rate, the low serum T3 during NTI or fasting results in reduction of the energy
      consumption of the body. This can be regarded as an adaptive mechanism to save
      energy, and thus to conserve protein and to protect organ function. The low serum
      T3 concentration should preferentially be maintained until recovery from illness
      or adequate calorie supply. This implies that the low serum T3 should not result
      in a rise in serum TSH. We postulate that different regulation of thyroid hormone
      transport into the relevant tissues, i.e., liver and pituitary, may play a role
      in maintenance of the low T3 production during NTI and fasting. This hypothesis
      is further elaborated in this paper by comparing (i) the properties of the
      thyroid hormone uptake mechanism in rat and human hepatocytes, perfused rat
      liver, and rat anterior pituitary cells, and (ii) the effects of fasting and
      conditions that mimic NTI on thyroid hormone transport in the same preparations.
      In addition, the consequences of changes in thyroid hormone transport and
      peripheral thyroid hormone metabolism during fasting and NTI for the serum level
      of rT3 and for TSH secretion are discussed. The data are compatible with the
      existence of different transport systems for thyroid hormone in liver and
      pituitary. We suggest that these different thyroid hormone carriers allow tissue
      specific regulation of the intracellular availability of T3.

PMID- 8875762
TI  - Histomorphological aspects of the development of thyroid autoimmune diseases:
      consequences for our understanding of endocrine ophthalmopathy.
AB  - In this short review we will first evaluate the histomorphological aspects of the
      human and spontaneous animal thyroid autoimmune diseases. These diseases include
      Hashimoto goiter, primary myxedema, Graves' disease, and the spontaneous forms of
      thyroiditis in the Bio Breeding (BB) rat, the nonobese diabetic (NOD) mouse, and
      the obese strain (OS) of chicken. Based on sequential histomorphological events
      in the animal models of thyroid autoimmune disease, a mechanism for the
      pathogenesis of thyroid autoimmune disease is proposed. Since one of the human
      thyroid autoimmune diseases, specifically Graves' disease, is often associated
      with ophthalmopathy, the histomorphological aspects of the ophthalmopathic
      process are also evaluated to consider its possible autoimmune character.

PMID- 8875763
TI  - Biological markers for the clinical diagnosis of Alzheimer's disease.
AB  - There is a compelling need to develop biological marker(s) to confirm a clinical
      diagnosis of Alzheimer's disease (AD) during life in order to unequivocally
      identify AD patients for emerging therapeutic interventions. This review
      describes recent advances in the development of diagnostic marker(s) for AD. They
      include polymorphism of apolipoprotein E (ApoE) and alpha 1-antichymotrypsin as
      well as cerebrospinal fluid (CSF) tau and CSF-amyloid beta-protein levels, skin
      biopsy, and pupil dilatation assay by anti-cholinergic agent. In conclusion, ApoE
      genotyping should not be used as a sole diagnostic test for AD, and that
      monitoring of CSF-tau appeared to be most promising and reliable diagnostic aid.

PMID- 8875764
TI  - Lung microvascular pressure profile in acute lung injury.
AB  - To clarify the role of microvessels in the development of pulmonary hypertension
      of acute lung injury, we induced lung edema by oleic acid (OA) in ten
      artificially perfused cat lungs and measured microvascular pressure. Pulmonary
      artery pressure (Ppa) and pressure of 30-50 microns arteriole (Parteriole)
      increased from 19.2 +/- 1.4 and 15.7 +/- 1.0 cmH2O before to 30.5 +/- 5.0 cmH2O
      and 22.7 +/- 2.4 cmH2O after edema, respectively. Pressure of 30-50 microns
      venule (Pvenule) and venous occlusion pressure (Pvo) did not change significantly
      after edema. Double occlusion pressure (Pdo) which represents pulmonary
      microvascular pressure increased from 14.5 +/- 0.6 to 17.7 +/- 2.0 cmH2O.
      Pressure gradient in the artery, i.e., between Ppa and Parteriole and in the
      microvessels, i.e., between Parteriole and Pvenule increased when lung became
      edematous. Pressure gradient in vein, i.e., between Pvenule to left atrium was
      not affected by edema. Pdo was in the midst of Parteriole and Pvenule in both
      edematous and non-edematous lung. In acute lung injury, increase of microvascular
      resistance was followed by an increase of arterial resistance and caused
      pulmonary hypertension.

PMID- 8875765
TI  - Early gastric cancer in young adults.
AB  - The clinicopathological features of 31 young patients with early gastric cancer,
      defined as under 40 years of age, were reviewed retrospectively from hospital
      records between 1969 and 1993. The results were compared with those for 549
      patients 40 years of age or older. Early gastric cancer was found in 36.0% of the
      younger patients with gastric cancers and in 36.3% of the older patients with
      those. The gender ratio of m/f was 1.21 for the younger patients and 2.37 for the
      older patients. The macroscopic characteristics of early gastric cancer for the
      younger patients were superficial depressed lesions and a larger tumor size. The
      distinguished histologic features of early gastric cancer for the younger
      patients were a diffuse type of cancer and infiltrative tumor growth with a
      scirrhous stroma. More extensive lymph node dissection was performed on the
      younger patients than on the older patients. The younger patients had a prognosis
      similar to that of the older patients. We conclude that early gastric cancer in
      young patients possesses histological aggressiveness, but those patients rather
      show a similar survival to older patients.

PMID- 8875766
TI  - Effect of carnitine administration on glycine metabolism in patients with
      isovaleric acidemia: significance of acetylcarnitine determination to estimate
      the proper carnitine dose.
AB  - In isovaleric acidemia (IVA), accumulated isovaleryl-CoA in the mitochondrion
      induces variable metabolic disturbances. To remove intramitochondrial isovaleryl
      groups, glycine therapy has been advocated primarily. On the other hand,
      secondary carnitine deficiency has been documented in this disorder and carnitine
      supplementation alone has been reported to be effective. In the present study, we
      administered carnitine and glycine to patients with IVA, and investigated serum
      carnitine and urinary excretion of total and free carnitine, acylcarnitine
      profile (i.e., isovalerylcarnitine and acetylcarnitine), and isovalerylglycine.
      By adding carnitine to glycine supplementation, more isovalerylglycine, not only
      isovalerylcarnitine, was excreted in the urine. Acetylcarnitine was detected in
      the urine only when sufficient carnitine was supplemented. We concluded that
      combined therapy of glycine and carnitine is more effective and safer to
      eliminate isovaleryl-CoA in IVA than conventional therapy using either glycine or
      carnitine. Urinary acetylcarnitine concentration might be a good marker
      indicating the optimal dose of L-carnitine supplementation.

PMID- 8875767
TI  - The incidence of respiratory tract pathogens and antimicrobial susceptibilities
      of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella)
      catarrhalis isolated between 1990 and 1993.
AB  - Using a quantitative culture of sputum, the incidence of pathogenic bacteria in
      respiratory infection in our laboratory between 1990 and 1993 were investigated.
      While Haemophilus influenzae, Streptococcus pneumoniae and Moraxella
      (Branhamella) catarrhalis were isolated at high rates (67-78%) from the specimens
      of outpatients throughout the study period, the incidence of S pneumoniae has
      increased gradually. The antimicrobial susceptibilities of these three pathogens
      were examined with the agar dilution method. A marked increase of penicillin (PC)
      resistant S. pneumoniae (MIC > or = 0.1 microgram/ml) was observed with a
      resistance rate of 2.1% in 1990 and 25% in 1993. Resistance to erythromycin (EM,
      MIC > or = 1.56 micrograms/ml) was 8.5% in 1990 but then increased to 34% in
      1992. Most of the PC resistant isolates were resistant to multidrugs such as EM,
      minocycline and clindamycin. The MICs of all beta-lactams examined for S.
      pneumoniae increased along with the MICs of PC, though the level varied between
      drugs. The rates of beta-lactamase positive H. influenzae gradually decreased,
      being 14.3% in 1990 and 7.4% in 1993, whereas those of M. (B) catarrhalis were
      consistently high (> 90%) every year. In addition to beta-lactamase production,
      the emergence of strains of H. influenzae and M. (B) catarrhalis resistant to new
      quinolone drugs should be noted.

PMID- 8875768
TI  - Bilateral aldosterone-producing adenomas in two patients diagnosed by
      immunohistochemical analysis of steroidogenic enzymes.
AB  - Bilateral adrenal aldosterone-producing adenomas (APA) are rare. It is important
      to distinguish bilateral APA from idiopathic hyperaldosteronism (IHA) which is
      due to bilateral hyperplasia of the adrenal cortex. We present two patients with
      bilateral APA in whom the diagnosis was made histochemically by analyzing
      steroidogenic enzymes. They showed hypokalemia, high plasma aldosterone
      concentration (PAC) and suppressed plasma renin activity (PRA). Bilateral adrenal
      tumors were represented by computed tomography, and surgical resection was
      performed. In both cases, cytochrome P-450 and other enzymes that were involved
      in aldosterone synthesis were found mainly in tumor, but little in the zona
      glomerulosa of the adjacent adrenals, which showed paradoxical hyperplasia. Such
      cases are difficult to distinguish from IHA. The two disorders were
      differentiated by immunohistochemical analysis of steroidogenic enzymes.

PMID- 8875769
TI  - Scanning electron microscopy of fragmentary marker chromosomes observed by light
      microscopy.
AB  - To study the fine structure of fragmentary marker chromosomes, we performed
      scanning electron microscopy (SEM) on samples isolated from two carriers (Case 1:
      46, XY/47, XY, +mar/48, XY, +mar, +mar; Case 2: 47, XY, +mar). In both cases,
      light microscopic observation revealed that marker chromosomes lacked a
      centromere and were fragmented in appearance. However, SEM observation of the
      metaphasic cells in both cases showed three variations. One variation was a
      structure that seemed to be metacentric, another was a structure that seemed to
      be submetacentric, and the remaining one was essentially fragmentary. However,
      neither the usual chromatid nor centromere formations were observed in the
      metacentric-like and submetacentric-like structures, even when both cases were
      observed by SEM. Moreover, the marker chromosomes of the boy of Case I, who
      suffered from various clinical troubles, included a greater population of
      metacentric-like or submetacentric-like structures than of essentially
      fragmentary structures. The marker chromosomes of the fetus of Case 2, who
      suffered from no clinical problems, included a much greater population of
      essentially fragmentary structures than metacentric-like or submetacentric like
      structures. Therefore, SEM observation of fragmentary marker chromosomes that are
      visible on light microscopy might be used to define specific structures.
      Moreover, SEM observation might provide clinical criteria relating to the
      pathogenesis of fragmentary marker chromosomes found on light microscopy.

PMID- 8875770
TI  - Phospholipase A2--a structural review.
AB  - Phospholipases A2 (PLA2) are widely distributed in nature and are well
      characterized proteins with respect to their catalytic and pharmacological
      activities. A wealth of structural information has recently become available both
      from X-ray diffraction and NMR studies, and although a detailed model of the
      catalytic mechanism of PLA2 has been proposed, the structural bases of other
      aspects of PLA2 function, such as interfacial activation and venom PLA2
      pharmacological activities, are still under debate. An appreciation of the PLA2
      protein structure will yield new insights with regard to these activities. The
      salient structural features of the class I, II and III PLA2 are discussed with
      respect to their functional roles.

PMID- 8875771
TI  - Fab fragments of the monoclonal antibody BCF2 are capable of neutralizing the
      whole soluble venom from the scorpion Centruroides noxius Hoffmann.
AB  - BCF2 is a murine hybridoma cell line that produces a neutralizing antibody
      against toxin 2 (Cn2) from the scorpion Centruroides noxius Hoffmann of Mexico.
      In this communication we report the preparation and use of the BCF2 antibody and
      its antigen binding fragments (Fab) in experiments aiming at obtaining protection
      of experimental albino mice (strain CD1) challenged with purified toxin Cn2, as
      well as, with whole soluble venom from C. noxius. The monoclonal antibody BCF2 in
      amounts of 1 mg neutralizes 28 LD50 of soluble venom of C. noxius, whereas the
      Fab fragments of BCF2 (1 mg) are capable of neutralizing 43 LD50 dose of the same
      venom. To reach the same level of neutralization, with the commercially available
      horse antiserum [F(ab')2], we need to use about ninefold more material.

PMID- 8875772
TI  - Protonophore antagonism of botulinum toxin in mouse muscle.
AB  - Botulinum neurotoxins (BoNT) are thought to enter cells through endocytotic
      vesicles where acidification is required for release of these toxins into the
      cytoplasm. Two ionophores, nigericin and monensin, that increase membrane
      permeability to H+ and K+ or H+, Na+ and K+, respectively, block vesicle
      acidification by acting as H+ shunts to neutralize pH gradients. Nanomolar
      concentrations of nigericin or monensin delayed development of blockade in BoNT-A
      or BoNT-B treated muscles two-to threefold over onset times in unprotected
      muscles. However, higher concentrations of the ionophores directly blocked
      synapses. Thus, nigericin and monensin could delay onset of BoNT paralysis only
      over a narrow range of concentrations.

PMID- 8875773
TI  - Toxic effects of blooms of marine species of Oscillatoriales on farmed prawns
      (Penaeus monodon, Penaeus japonicus) and brine shrimp (Artemia salina).
AB  - Benthic and planktonic blooms of species of Oscillatoriales coincided with
      mortalities of Penaeus monodon during four episodes at Australian prawn farms.
      Oscillatoria corakiana was the dominant planktonic species at 65-90,000 cells/ml,
      but Spirulina sp., Lyngbya sp., Oscillatoria sp. and Nodularia sp. were also
      identified from the water column, benthic layers or surface mats. The levels and
      variety of Vibrionaceae in prawn tissue, suggest that mortalities were caused by
      secondary infections of bacteria. However, experimental results indicate that
      toxicity of the blooms of Oscillatoriales was the primary cause of disease. Pond
      water and extracts from a tank culture of benthic Oscillatoriales caused
      mortalities when injected into P. monodon and P. japonicus. Immersion of artemia
      in extracts from the tank culture also caused mortalities, with L.D50 values for
      the supernatant extract of 70 mg/litre for artemia cysts and 50 mg/litre for
      adult artemia, and LD50 values for the pellet extract of 110 mg/litre for artemia
      cysts and 200 mg/litre for adult artemia. Experiments with artemia suggested the
      blooms of Oscillatoriales produced water-soluble, heat-labile toxin/s.
      Mortalities may have been caused by a neurotoxin because: (a) there was a lack of
      histopathological evidence of damage to the digestive tracts of prawns during
      each episode; and (b) artemia cysts immersed in extracts of Oscillatoriales died
      before they developed digestive tracts. PSP toxin, anatoxin-a, homoanatoxin-a and
      microcystins were not detected when pond water from a diseased pond was tested.
      It is proposed that sub-lethal levels of toxin weakened the prawns, causing
      reduced feeding behaviour and an impaired immune system. As a result, prawns were
      prone to secondary infection by pathogenic bacteria. Because Oscillatoriales are
      ubiquitous in prawn farms, the findings have significant implications for the
      assessment of disease in the prawn farming industry.

PMID- 8875774
TI  - Purification of anticoagulant factor from the spine venom of the crown-of-thorns
      starfish, Acanthaster planci.
AB  - The fraction with anticoagulant activity was purified from the spine venom of
      Acanthaster planci by fractionation with ammonium sulfate followed by column
      chromatography and designated plancinin. Its molecular weight determined by
      tricine-SDS polyacrylamide gel electrophoresis was about 7500 in native form and
      about 3000 in reduced conditions. Plancinin showed neither platelet aggregation
      nor an enhancement of vascular permeability. Fibrin formation time was prolonged
      by 25 micrograms of plancinin which was comparable to 0.08 units of heparin. 2
      Mercaptoethanol inhibited the anticoagulant activity of plancinin with a 50%
      inhibition concentration of 5.6 x 10(-3) M. The bleeding time of mice was
      significantly prolonged by i.v. administration of plancinin and this effect was
      lost when plancinin was given orally or s.c. These data indicate that plancinin
      is a peptide with disulfide bond which is essential for the anticoagulant
      activity.

PMID- 8875775
TI  - Toxicological biotest on Diptera larvae to detect ciguatoxins and various other
      toxic substances.
AB  - A toxicological test was developed using a new animal sensitive to various
      toxins, especially ciguatoxin (CTX), which poisons humans who eat tropical
      fishes. The larvae of Parasarcophaga argyrostoma (Diptera, Sarcophagidae) were
      selected for their marked ability to consume spontaneously large quantities of
      various proteins; meat, fish flesh or liver, mussels, etc. Larvae grown on meat
      overnight can easily be observed without requiring optical instruments. Ten
      larvae were placed on 5 g of the sample to be tested, and left for 3-24 hr.
      Samples containing > 1 ng of CTX/g of flesh (moray.eel CTX) killed the larvae in
      about 3 hr; samples with lower concentrations inhibited larval growth, which can
      be noted with the marked eye. These readings were rendered objective by weighing
      the larvae before and after their being placed on the test sample and comparing
      the result to that of the control. The reading with the naked eye seems to be
      satisfactory up to 0.2 ng of CTX/g, while that by weighing was acceptable up to
      0.10-0.15 ng/g. The coefficient of variation in the sensitive zone (approximately
      50% of normal growth) was about 25% for a series of 11 experiments. P.
      argyrostoma larvae are sensitive to various other toxic substances, such as
      tetrodotoxin, okadaic acid, aflatoxin B1 and amanitin. The test is extremely
      simple in its theory and practice. It does not require complex materials or
      equipment and it is very inexpensive. It could be used to detect ciguatera toxins
      in the monitoring of fishing areas and for the commercialization of big-sized
      fish.

PMID- 8875776
TI  - Effect of Habu (Trimeresurus flavoviridis) antivenom on changes of hemostatic
      parameters following administration of crude venom from T. flavoviridis in
      rabbits.
AB  - We carried out experiments to examine the efficacy of Habu antivenom in relation
      to variations of hemostatic parameters induced by the administration of crude
      venom to rabbits. For neutralization of the crude venom by Habu antivenom, the
      correlation between the concentrations of Habu antivenom (Y) and crude venom (X)
      was expressed by the equation: Y = -0.473 + 0.539X. We examined the variations in
      hemostatic parameters in the state which crude venom was neutralized by Habu
      antivenom following the administration of crude venom (1 mg/kg) from Trimeresurus
      flavoviridis. Although the hemostatic parameters [level of fibrinogen,
      antithrombin III (AT-III) activity and alpha 2-plasmin inhibitor (alpha 2-PI)
      activity] underwent decreases after the administration of crude venom, they
      revealed fluctuations within the normal range after the Habu antivenom
      administration. The AT-III activity, however, decreased gradually until 90 min
      after the antivenom administration. These results suggested that Habu antivenom
      was effective in improving the abnormal coagulant activity induced by crude
      venom. However, the neutralization effect towards the coagulant activity of crude
      venom by the Habu antivenom did not continue for a long time and did not lead to
      recovery of the AT-III activity. Since excessive doses of antivenom can induce
      serious medical problems, we expect that simultaneous use of antivenom and AT-III
      preparation, instead of excessive and single use of Habu antivenom could provide
      a useful therapy for snake bites from the present study.

PMID- 8875777
TI  - Alpha 2-macroglobulin of rabbits inhibits the habutobin activity.
AB  - We have investigated whether alpha 2-macroglobulin (alpha 2M) of rabbits inhibits
      the activity of habutobin, a thrombin-like enzyme from Trimeresurus flavoviridis
      venom. Rabbit alpha 2M was purified with ultracentrifugation, gel filtration on
      Sepharose 6B and ion exchange chromatography on DEAE-Sephacel. Inhibitory effects
      of rabbit alpha 2M on habutobin was determined by the fibrin forming activity,
      digestion of A alpha chain of fibrinogen, and the release of fibrinopeptide A
      from fibrinogen. As a results, purified alpha 2M showed a single band with high
      molecular weight, around 800,000 mol. wt by means of polyacrylamide gel
      electrophoresis using PhastSystem. Besides inhibiting amidolytic and caseinolytic
      activity of porcine trypsin, it has inhibited the activity of habutobin: that is,
      in the presence of rabbit alpha 2M, fibrin forming activity of habutobin was
      decreased and habutobin-induced digestion of A alpha chain was inhibited. In
      addition, rabbit alpha 2M reduced habutobin-induced release of fibrinopeptide A
      from rabbit fibrinogen.

PMID- 8875778
TI  - Noxiustoxin 2, a novel K+ channel blocking peptide from the venom of the scorpion
      Centruroides noxius Hoffmann.
AB  - A novel peptide called Noxiustoxin 2 (NTX2) was purified from the venom of the
      scorpion Centruroides noxius and characterized chemically and functionally. It is
      composed of 38 amino acid residues linked by three disulfide bridges and its
      primary structure is 61% identical to that of Noxiustoxin (NTX). It is not toxic
      to mice (using up to 200 micrograms/20 g mouse weight) and crustaceans (up to 30
      micrograms/g of crayfish), but has a paralysing effect on crickets (30
      micrograms/g animal). It displaces the binding of [125I]NTX to rat brain
      synaptosome membranes with a Ki of 0.1 microM, in comparison NTX has a Ki of 100
      pM. Similarly, using single Ca2+ activated K+ channels of small conductance
      obtained from cultured bovine aortic endothelial cells it was shown that NTX2 is
      over two logarithm units less potent than NTX in producing 50% blockade of the
      probability of opening the channels. NTX2 is not recognized by a panel of six
      distinct monoclonal antibodies against NTX, however it is recognized by
      polyclonal antibodies raised in mouse, with native NTX. Primary structure
      comparison of both NTX and NTX2 suggests that the N-terminal segments of these
      peptides are important for channel affinity.

PMID- 8875779
TI  - First report of pectenotoxin-2 (PTX-2) in algae (Dinophysis fortii) related to
      seafood poisoning in Europe.
AB  - Pectenotoxin-2 (PTX-2), a polyether-lactone included in the neutral class of
      diarrhoetic shellfish poisoning (DSP) toxins, has been unambiguously detected in
      Dinophysis fortii collected in the northern Adriatic Sea (Emilia Romagna coasts).
      This is the first report of such a toxin in Europe. This lipid soluble toxin was
      identified both in crude methanolic phytoplankton extract and in the neutral
      fraction obtained by extract chromatography on a basic alumina column. The
      techniques used were reversed phase high-performance liquid chromatography
      followed either by UV diode-array detection (LC-UV-DAD) or by mass spectrometry
      (LC-MS) and tandem mass spectrometry (LC-MS-MS) using an atmospheric-pressure
      ionization source and an ionspray interface. Okadaic acid (OA) was also found in
      the D. fortii specimens and quantified as 15 pg/cell. Although quantitation of
      PTX-2 was not possible due to the lack of pure toxin, the high PTX-2:OA ratio
      suggested PTX-2 was significant in the D. fortii specimens. The presence of PTX-2
      in a region with no previous report of DSP neutral toxic compounds may indicate a
      risk of human poisoning. Serious efforts should therefore be made to develop
      suitable routine methods capable of detecting the presence of PTXs in biological
      materials of marine origin, in order to assure the wholesomeness of seafood
      products.

PMID- 8875780
TI  - Okadaic acid induces changes in the organization of F-actin in intestinal cells.
AB  - Okadaic acid, a polyether fatty acid associated with diarrhetic seafood
      poisoning, is capable of inhibiting protein phosphatases 1 and 2A which are
      considered among the major protein phosphatases in the cytosol of mammalian
      cells. One of the substrates for these phosphatases has been reported to be the
      cytoskeleton. In this paper, we focused on the effects of okadaic acid in
      intestinal cells, the more physiological target for this toxin. By fluorescence
      and scanning electron microscopy, we evidenced a dose- and time-dependent effect
      on F-actin which preceded any detectable change of tubulin and vimentin network.
      By a flow cytometric approach, we observed that plasma membrane permeability and
      transmembrane potential, two indicators of early cell damage or activation,
      respectively, remained unaffected in intoxicated cells. The present data strongly
      support the theory that actin is one of the main cytosolic targets for the
      phosphatases inhibited by okadaic acid in intestinal cells.

PMID- 8875781
TI  - Determination of okadaic acid content of dinoflagellate cells: a comparison of
      the HPLC-fluorescent method and two monoclonal antibody ELISA test kits.
AB  - Total okadaic acid (okadaic acid plus methylokadaic acid) in acclimated clones of
      the dinoflagellates Prorocentrum hoffmannianum and P. lima was determined using
      the HPLC-fluorescent method, UBE ELISA test kit, and Rougier ELISA test kit. The
      nonokadaic acid-producing species. Amphidinium klebsii, Prorocentrum mexicanum,
      P. micans, P. cassubicum, and Gambierdiscus toxicus were examined using the same
      methods of analysis. All three methods yielded consistent results for P.
      hoffmannianum which produces only okadaic acid. However, results of the three
      methods were not consistent for P. lima which produces both okadaic acid and
      methylokadaic acid. The UBE ELISA demonstrated little or no cross-reactivity with
      methylokadaic acid; whereas, the Rougier ELISA demonstrated varying degrees of
      cross-reactivity with that analog. Analyses of nonokadaic acid producing-species
      yielded negative results, with one exception. The Rougier ELISA demonstrated
      reactivity with extracts of G. toxicus. Since outbreaks of DSP may be caused by
      okadaic acid, methylokadaic acid, or a combination of these toxins, both ELISA
      kits may underestimate total toxin present in toxic shellfish.

PMID- 8875782
TI  - Resistance and vulnerability of crustaceans to cytolytic sea anemone toxins.
AB  - Crustaceans (Mithraculus, Neopetrolisthes, Periclimenes, Stenorhynchus sp.)
      living in association with sea anemones, shore crabs (Metopograpsus oceanicus)
      and brine shrimps (Artemia salina) were found to be resistent to the exposure of
      cytolytic sea anemone toxins (up to 100 micrograms/ml) and to other membrane
      active compounds such as gramicidin A and saponin. The gill filaments of the
      crustaceans were not affected, indicating that the chitin layer protects the
      epithelium from the action of the cytolytic toxins. However, crustaceans are
      highly susceptible to sea anemone toxins when injected parenterally.

PMID- 8875783
TI  - Effect of fasciculin on hydrolysis of neutral and choline esters by
      butyrylcholinesterase, cobra venom and chicken acetylcholinesterases.
AB  - Acetylcholinesterases (AChEs) very sensitive to fasciculin inhibition (KiS in
      picomolar range) have a distinctive group of aromatic amino acids in the
      peripheral region (Y70, Y121, W279 in Torpedo AChE). Enzymes that lack these
      amino acids like butyrylcholinesterases (BChEs) or one or two of them like cobra
      venom, insect and chicken AChEs are 1000 to 1,000,000 times less sensitive.
      Fasciculin is a non-competitive inhibitor of the hydrolysis of choline and
      neutral esters by very sensitive AChEs. For the other group of enzymes,
      differences arise according to the type of substrate. Fasciculin still behaves as
      a non-competitive inhibitor with choline esters. In contrast, hydrolysis of
      phenylacetate was unaffected or slightly increased with BChEs and a partial
      competitive inhibition was observed with cobra venom and chicken enzymes.

PMID- 8875784
TI  - Bibliography of Toxinology.

PMID- 8875785
TI  - Epstein-Barr virus DNA in serum after liver transplantation--surveillance of
      viral activity during treatment with different immunosuppressive agents.
AB  - In immunocompromised HIV-infected and transplanted patients, there is a risk of
      developing Epstein-Barr virus (EBV)-associated lymphoproliferative disorders
      (LPD) and lymphomas. EBV has previously been detected by the polymerase chain
      reaction (PCR) in cerebrospinal fluid from all AIDS patients with EBV-associated
      cerebral lymphomas. We therefore thought it would be of interest to determine
      whether transplant patients with extracerebral EBV-associated LPD have detectable
      EBV genomes in serum. Nested PCR (nPCR) showed that 58% (18/31) of liver
      transplant (LTX) patients had EBV DNA in 17% (21/125) of serum samples obtained
      within the first 3 months after LTX. In 39% (7/18) of the patients, the first EBV
      nPCR-positive sample was found within 2 weeks post-LTX. Basic immunosuppression
      with cyclosporin A or FK506 did not seem to influence the frequency of detectable
      EBV genomes in serum. In contrast, positive EBV nPCR correlated to secondary OKT3
      treatment for severe acute rejection (P = 0.009). EBV-associated malignant
      lymphoma developed in three patients 2-6 months post-LTX. In all of them, EBV DNA
      was amplifiable within 12-14 days after LTX. The EBV antibody titers were not
      directly related to detectable EBV DNA in serum. We conclude that monitoring of
      LTX patients receiving increased immunosuppression by nPCR for EBV DNA in serum
      may help in the early identification of those at risk of developing EBV
      associated LPD.

PMID- 8875786
TI  - Hyaluronic acid uptake in the assessment of sinusoidal endothelial cell damage
      after cold storage and normothermic reperfusion of rat livers.
AB  - The uptake of hyaluronic acid (HA) was used to assess preservation damage to
      sinusoidal endothelial cells (SEC) during cold storage and subsequent
      normothermic reperfusion of rat livers. After 8, 16, 24, and 48 h storage in
      University of Wisconsin (UW) solution, livers were gravity-flushed via the portal
      vein with a standard volume of cold UW solution containing 50 micrograms/l HA.
      The effluent was collected for analysis of HA, aspartate aminotransferase (AST),
      and lactate dehydrogenase (LDH). The mean uptake of HA at 0 h was 59.1% +/- 4.6%
      (mean +/- SEM). After 8 h of storage, HA uptake was similar (55.5% +/- 7.3%),
      whereas after 16 h of storage it was reduced to 34.7% +/- 5.8%. At 24 and 48 h of
      storage, no uptake of HA was found. In a second series of experiments, livers
      were stored in UW solution and subsequently reperfused for 90 min with a Krebs
      Henseleit solution (37 degrees C) in a recirculating system containing 150
      micrograms/l HA. Following 8 h of storage, 34.6% +/- 8.0% of the initial HA
      concentration was taken up from the perfusate. After 16 and 24 h of storage, no
      uptake of HA was found. The results of this study indicate that damage to SEC
      occurs progressively during storage, leading to zero uptake of HA by the rat
      livers at 24 h of cold ischemia time. Additional reperfusion injury to the SEC
      was demonstrated by the reduced ability of the SEC to take up HA following
      normothermic reperfusion. The uptake of exogenous HA in preserved livers, used as
      a tool to assess SEC injury, enables the detection of early preservation damage.

PMID- 8875787
TI  - Impact of adhesion molecules of the selectin family on liver microcirculation at
      reperfusion following cold ischemia.
AB  - We investigated the role of adhesion molecules in the early phase of reperfusion
      following cold ischemia. Livers of male Lewis rats were preserved for 0 h (group
      A) or 24 h in University of Wisconsin (UW) solution without additives (group B)
      or in UW solution with anti-ICAM-1 antibody (group C) or anti-E-selectin-1,
      SLe(x) and SLe(a) antibodies (group D). The livers were then reperfused with
      diluted rat whole blood (DWB; groups A and B). DWB containing anti-ICAM-1 and LFA
      1 antibodies (group C) or DWB containing anti-L-selectin, SLe(x) and SLe(a)
      antibodies (group D). The reperfusion was performed at 37 degrees C for 1 h at 5
      cm H2O of perfusion pressure. During reperfusion, hepatic microcirculation was
      assessed by monitoring portal and peripheral tissue blood flow. Bile production
      was significantly reduced in group B livers compared with those in group A. Anti
      ICAM-1 and LFA-1 antibodies failed to improve hepatic microcirculation, whereas
      anti-LECAM-1, SLe(x) and SLe(a) antibodies significantly improved the
      microcirculation. Bile production in group C and D livers was comparable to that
      in group B livers. Preservation for 24 h significantly increased the release of
      TNF-alpha from 0.207 to 43.7 pg/g per hour during reperfusion. Monoclonal
      antibodies to the adhesion molecules did not suppress the release of TNF-alpha in
      groups C and D. Histological examination demonstrated a lack of leukocyte
      infiltration or thrombus in hetapic microvessels. The extent of hepatocyte
      necrosis did not differ among groups B, C, and D. We conclude that the
      microcirculatory disturbance in the early phase of reperfusion occurs as a result
      of the tethering of leukocytes through the interaction of the selectin family and
      their ligands, and that the ICAM-1-LFA-1 pathway is not involved in this step.
      The lack of improvement in bile production with antibodies to the selectin family
      and their ligands strongly suggests that other mechanisms participate in the
      deterioration of hepatic function.

PMID- 8875788
TI  - Intravital studies on beneficial effects of warm Ringer's lactate rinse in liver
      transplantation.
AB  - This quantitative in vivo fluorescence microscopy study investigated the impact
      of warm versus cold Ringer's lactate (RL) graft rinse on various microvascular
      manifestations of ischemia-reperfusion injury after liver transplantation in the
      rat. Syngeneic orthotopic liver transplantation, including arterial
      revascularization, was performed in male Lewis rats following 24 h of cold
      storage in University of Wisconsin (UW) solution. In one group (n = 8) liver
      grafts were rinsed with 4 degrees C (cold) RL, whereas in the other group (n = 8)
      grafts were rinsed with 37 degrees C (warm) RL immediately prior to
      revascularization. Hepatic microvascular perfusion, leukocyteendothelium
      interaction, and Kupffer cell activation were quantified 30-90 min after graft
      reperfusion by direct visualization with intravital fluorescence microscopy.
      Moreover, biliary excretory graft function was analyzed by determination of bile
      flow and bile salt excretion during the first 90 min after reperfusion. Compared
      to grafts rinsed with cold RL, acinar and sinusoidal perfusion were found to be
      significantly increased after rinsing the grafts with warm RL. The amount of
      nonperfused acini declined from 18.1% +/- 4.0% to 7.4% +/- 1.6% (P < 0.05), and
      the total percentage of perfused sinusoids increased from 80.1 +/- 1.4 to 88.4 +/
      1.2 (P < 0.001) after cold and warm rinse, respectively. After rinsing the graft
      with warm RL, WBC adherence in sinusoids and especially in postsinusoidal venules
      decreased significantly by 28% (P < 0.001) and 33% (P < 0.001), respectively.
      Kupffer cell activation was markedly reduced after rinsing with RL at 37 degrees
      C, as indicated by a decelerated adherence of latex particles injected 80 min
      after reperfusion. Excretory graft function was dramatically increased following
      warm RL rinse during the 90-min observation period. Bile flow was enhanced from
      1.04 +/- 0.5 to 3.9 +/- 0.8 ml/100 g liver per 90 min (P < 0.01), with a parallel
      rise in bile salt excretion from 24.3 +/- 5.8 to 128.0 +/- 19.8 mmol/ 100 g liver
      per 90 min (P < 0.05) when compared to cold RL. These data strongly suggest that
      rinsing liver grafts with warm RL prior to reperfusion represents a simple and
      inexpensive way to reduce the incidence of primary graft failure secondary to
      ischemia and reperfusion injury in liver transplantation.

PMID- 8875789
TI  - A single center evaluation of the Collaborative Transplant Study (CTS) DNA
      project.
AB  - Historical HLA class II serological typing results of transplantations performed
      in "The Leuven Collaborative Group for Transplantation" were subjected to
      retrospective Restriction Fragment Length Polymorfism (RFLP) DNA control typing
      by the Collaborative Transplant Study (CTS) DNA project using Polymerase Chain
      Reaction (PCR)-based DNA methods. We re-evaluated the serology/ RFLP-discrepant
      CTS DNA data for our local patients transplanted during a historical period
      (January 1988 until May 1992) before any class II DNA typing was performed in our
      tissue typing laboratory. These retyping results confirm both the CTS data for
      patient typing and the Eurotransplant data for donor typing. A confirmed high
      discrepancy rate of 19.0% (after exclusion of 2.2% transcription errors) was
      found in the patient population. A low discrepancy rate of 6.8% (after exclusion
      of 2.2% transcription errors) for the donor population is concordant with the
      Eurotransplant donor data. Only 4 of the 588 individuals were found to be
      incorrectly typed by the RFLP method; all involving the specificities DRB1*1102.
      This indicates that RFLP typing, as performed by the CTS DNA project, can be
      considered a valid, retrospective DNA typing system for the accurate
      interpretation of class II matching in organ transplantation. A second conclusion
      to be drawn from this study is the need for prospective DNA typing for kidney
      transplant recipients, as the discrepancy rate in this cohort is high. Our
      results suggest that with good quality serological HLA-DR typing, prospective
      donor DNA typing is not urgently needed.

PMID- 8875790
TI  - Pharmacokinetics of a new microemulsion formulation of cyclosporin A (Neoral) in
      young patients after renal transplantation.
AB  - Pharmacokinetics of the new galenic formulation of cyclosporin A, Neoral,
      (Sandoz) was examined in 12 stable young patients after renal transplantation.
      Six of these patients were tested before and 4 weeks after switching from the
      standard formulation Sandimmun to Neoral. No significant changes were observed in
      trough levels, Lmax, Cmax, and AUC0-12 h, but the absorption rate constant (Ka)
      increased (P = 0.03). Glomerular filtration rate, as assessed by inulin
      clearance, increased by more than 10% in three patients and decreased in two, and
      was usually associated with a respective drop and rise in Cmax and AUC0-12 h of
      cyclosporin A. The large interindividual variability in the response to the
      conversion to the new formulation points to a need for close monitoring of
      cyclosporin A trough levels and renal function after switching from Sandimmun to
      Neoral in this age group in order to avoid nephrotoxicity.

PMID- 8875791
TI  - Lipids, lipoprotein (a) and coronary artery disease in patients following cardiac
      transplantation.
AB  - Cardiac allograft vascular disease (CAVD) is the most important cause of late
      mortality in cardiac transplant recipients. While the pathogenesis of the disease
      is believed to be immunological, other factors like hyperlipidaemia may
      contribute. Total cholesterol, LDL cholesterol. HDL cholesterol, triglycerides,
      apolipoprotein A1 and B and Lp(a) levels were measured in 174 cardiac transplant
      recipients attending our clinic for routine follow-up. Univariate and
      multivariate logistic regression analysis was carried out to assess the
      relationship of the variables studied to the presence of CAVD diagnosed with
      coronary angiography. CAVD was present in 42 of the 174 patients. The group with
      CAVD had a higher total cholesterol (6.8 vs 6.3 mmol/l), lower HDL cholesterol
      (0.8 vs 0.9 mmol/l), higher triglyceride (2.8 vs 2.0 mmol/l) and higher Lp(a)
      level (317.5 vs 95 mg/l) than the group without CAVD. In multivariate analysis,
      after adjusting for gender, hypertension, time from transplantation, preoperative
      diagnosis and lipid-lowering therapy, Lp(a), total cholesterol, HDL cholesterol
      and triglycerides remained significantly correlated with CAVD. The results
      indicate a significant association between hyperlipidaemia, Lp(a) levels and
      allograft vascular disease. Further studies are needed to show whether treatment
      of hyperlidaemia in this population delays the onset or slows the progression of
      CAVD.

PMID- 8875792
TI  - Combined liver and kidney transplantation.
AB  - Patients with end-stage renal and hepatic failure may be treated with combined
      liver and kidney transplantation (CLKTx). We reviewed the indications and
      outcomes of 16 CLKTx performed at the University of Minnesota between 1980 and
      1994. The majority of the recipients (87.5%) were young patients affected by
      congenital hepatic anomalies and concomitant end-stage renal failure. Fourteen
      were treated with cyclosporin-based immunosuppression and had an excellent
      outcome: with an average of 6 years of follow-up, patient survival was 85.7%,
      liver graft survival 85.7%, and kidney graft survival 72%. The incidence of
      rejection episodes was similar to the rate of rejection in our solitary kidney
      and liver transplants. In conclusion, our experience supports the value of CLKTx
      in treating patients with simultaneous failure of both organs or with congenital
      enzymatic hepatic deficits leading to renal failure.

PMID- 8875793
TI  - Renal fibrosis in cyclosporin A-treated renal allograft recipients: morphological
      findings in relation to renal hemodynamics.
AB  - Nineteen nondiabetic kidney graft patients treated with cyclosporin A for 2 years
      underwent percutaneous renal allograft biopsy as well as renal hemodynamic
      examination. Renal allograft fibrosis was quantitatively evaluated as the
      relative volume of the renal cortical interstitium (VV %) and as the
      interstitium/tubuli ratio (I/T ratio). The histological changes were then
      classified into four groups, depending on the degree of interstitial fibrosis.
      The glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow
      (RBF), filtration fraction (FF), and fractional clearance of sodium, potassium,
      phosphate, chloride, osmoles, and free water clearance were determined in all
      patients and in 13 healthy controls. Kidney graft recipients had significantly
      lower GFR, lower RPF, and lower RBF than the healthy controls (P < 0.001 for all
      comparisons) while FF was similar in patients and controls. Transplant recipients
      had a significantly higher fractional excretion of sodium, potassium, chloride,
      and phosphate than controls. All except one patient had clearly increased VV
      values, indicating increased interstitial fibrosis. The mean VV in renal
      allograft patients was 35% +/- 10% (normal < 16% +/- 5%) and the I/T ratio was
      1.07 +/- 0.60 (normal < 0.24 +/- 0.08). No correlation was found between the
      quantitative or semiquantitative biopsy analysis and any renal hemodynamic
      parameter measured. We conclude that renal function is significantly decreased in
      kidney graft recipients, but that adaptive tubular changes occur in the graft.
      Interstitial renal fibrosis was common but did not correlate to any renal
      functional parameter.

PMID- 8875794
TI  - Liver allograft rejection in rats depleted of CD8+ cells.
AB  - The mechanism(s) of rejection or tolerance induction is a competitive, complex
      process that presumably involves interactions between multiple subpopulations of
      T lymphocytes. We investigated the roles of CD8+ cytolytic and CD4+ helper T
      cells in rat strains that tolerate liver allografts and that differ at both the
      major histocompatibility complex (MHC) (RT1) and minor histocompatibility genes.
      Orthotopic liver transplantation (OLT) with arterial reconstruction was performed
      with Brown Norway (BN) (RT1n) donors and Lewis (RT1(1)) recipients, some of which
      were untreated, others treated with anti-CD8 antibody, and still others treated
      with anti-CD4 antibody. Liver graft rejection was monitored for 28 days on the
      basis of two criteria: (1) serum levels of AST enzyme at 3-day intervals and (2)
      liver biopsies at weekly intervals and at the time of sacrifice at the end of the
      study period. In the untreated control group, an elevation of AST was found to
      peak at day 6 after grafting, and it remained elevated until day 28 (AST 542 +/-
      72 U/l). Histologically, signs of severe rejection were first observed on day 9;
      these changed to moderate rejection about day 21 and to mild rejection by day 28,
      when the animals were sacrificed. Recipients pre-treated with anti-CD8
      demonstrated a significant elevation of AST within 6 days that, unlike in the
      control recipients, continued to rise sharply through the observation period (AST
      1127 +/- 181 U/l, P = 0.009 vs control group). Liver biopsies showed mild
      rejection at day 9 and moderate rejection at days 21 through 28. Recipients
      pretreated with anti-CD4 showed a time course of enzyme elevation and severity of
      rejection that was not significantly different from that observed in the control
      group. However, anti-CD4 treatment resulted in only 75% depletion of CD4+ cells
      in peripheral blood as compared to complete elimination of CD8+ cells following
      anti-CD8 treatment. Functional studies of spleen and liver-infiltrating
      lymphocytes obtained after 28 days showed low proliferative response in mixed
      lymphocyte culture with both BN and PVG stimulator spleen and lymph node cells.
      These results suggest that in this donor/recipient combination, removal of CD8+
      cells increases the severity of rejection as demonstrated by a progressive rise
      in AST and histology. Moreover, OLT in this combination results in a profound,
      nonspecific inhibition of proliferative T-cell responses to MHC alloantigens.

PMID- 8875795
TI  - Pure red cell aplasia after major ABO-incompatible bone marrow transplantation:
      two case reports of treatment with recombinant human erythropoietin.
AB  - A 34-year-old man with acute myelocytic leukemia (AML: MO) and a 32-year-old
      woman with AML: M2 developed pure red cell aplasia (PRCA) after receiving a major
      ABO incompatible bone marrow transplant (BMT). The first patient responded to
      recombinant human erythropoietin (rhEPO) therapy, while the second did not. The
      second patient also received methylprednisolone (m-PSL) but developed
      reticulocytosis and hemolysis after the administration of m-PSL. Plasmapheresis
      was then performed and the patient promptly recovered from hemolysis and PRCA. We
      conclude that close attention must be paid when treating PRCA following major ABO
      incompatible BMT with rhEPO and m-PSL, as there is always the potential for
      massive hemolysis.

PMID- 8875796
TI  - Successful management of hemolysis in ABO-nonidentical orthotopic liver
      transplantation by steroid therapy: a case report.
AB  - Hemolysis due to donor-derived B lymphocytes has been reported in patients who
      have undergone ABO-nonidentical orthotopic liver transplantation (OLT). Yet,
      until now, little was known about the management of this transplantation-induced
      hemolysis. In this report we describe our experience with hemolysis in a patient
      after OLT. In addition, based on theoretical assumption, we hypothesize that
      corticosteroids can be helpful in the management of ABO-nonidentical OLT-induced
      hemolysis.

PMID- 8875797
TI  - Venous thrombectomy in patients presenting with iliofemoral vein thrombosis after
      renal transplantation.
AB  - In this study 14 patients presented with 15 episodes of iliofemoral vein
      thrombosis after renal transplantation. Seven patients (group 1) had viable renal
      grafts and were treated with conventional anticoagulation. Eight patients (group
      2) had non-viable renal grafts and were subjected to graft nephrectomy and
      simultaneous venous thrombectomy without anticoagulation. The patients in group 2
      had rapid resolution of the signs and symptoms of the iliofemoral vein
      thrombosis, and noninvasive vascular investigation at follow-up revealed
      competent and patent deep veins in all patients. In contrast, only 50% of the
      patients in group 1 had normal venous studies at follow-up. We recommend that
      renal transplant recipients who develop iliofemoral vein thrombosis and nonviable
      allograft postoperatively should be subjected to venous thrombectomy at the time
      of graft nephrectomy.

PMID- 8875798
TI  - Pulmonary aspergillosis masquerading as progressive post-transplant lymphoma.
AB  - We report a patient with post-transplant lymphoma who was treated by renal
      allograft nephrectomy, discontinuation of immuno-suppressive therapy, and
      initiation of acyclovir administration. Despite these measures he appeared to
      have progressive lymphoma. Had a biopsy and cultures not been done, the diagnosis
      of aspergillosis would have been missed and the patient might have been treated
      with chemotherapy, with a potentially lethal outcome. Data from the Cincinnati
      Transplant Tumor Registry indicate that of 662 patients treated for
      posttransplant lymphoma, 277 patients died of cancer and 137 died of other
      causes, of which infection was a major factor. This case emphasizes the
      importance of proper work-up of patients with apparently progressive lymphomas.

PMID- 8875799
TI  - A quick technique for en bloc liver and pancreas procurement.

PMID- 8875800
TI  - Haemolytic uraemic syndrome associated with OKT3.

PMID- 8875801
TI  - Liver retransplantation for alcoholic cirrhosis recurring within a 21-month
      period.

PMID- 8875802
TI  - Experimental study of alleviation of hypertension, diabetes and pain by radon
      inhalation.
AB  - Indications for treatment at the Misasa Hot Spring, a radon producing radioactive
      spring, include hypertension, diabetes mellitus and pain. To clarify its
      mechanisms of action on these conditions, we evaluated dynamic changes in blood
      components such as vasoactive substances after radon inhalation. Vasodilation,
      alleviation of diabetic symptoms and morphine-like analgesic effects were
      observed, suggesting that these changes constitute part of the mechanisms of the
      radon spring therapy on the above conditions.

PMID- 8875803
TI  - Enhanced proliferation and IL-1 production of mouse splenocytes by low-dose whole
      body X-irradiation.
AB  - To elucidate the stimulative effect of low-dose whole-body X-irradiation on the
      immune system, in vivo, we studied its effects on some immune functions of mouse
      splenocytes. Results show that Concanavalin A (Con A) and phytohemagglutinin
      (PHA) responses of splenocytes were significantly increased by irradiation of 2.5
      cGy and 5 cGy, whereas lipopolysaccharide (LPS) response was significantly
      depressed by irradiation of 5 cGy. By irradiation of 2.5 cGy, Con A response was
      significantly accelerated at each concentration of Con A, but the optimum
      concentration of Con A shifted to a higher value of 4 micrograms/ml from 2
      micrograms/ml in the control group. When blood plasma obtained from 2.5 cGy
      irradiated mice was added into the medium at 0.005-1%, the Con A response of
      splenocytes in another un-irradiated mouse was significantly accelerated over
      that where the plasma added came from the sham-irradiated control mice.
      Furthermore, 2.5 cGy whole-body irradiation also enhanced the biological activity
      of intracellular interleukin-1 (IL-1) of LPS-stimulated splenocytes.

PMID- 8875804
TI  - Viruses--a conundrum.
AB  - To understand the pathophysiology of a disease, it is important to know the
      origin, causes and effects. This also helps to control and to treat the disease.
      In virus infections, it is difficult and confusing when the origin is sought. In
      this article it is hypothesized that the viruses, which are nucleoproteins, arise
      as fragments or broken segments of DNA or RNA. Various factors, such as
      radiation, toxic chemicals, pollution, are listed as possible causes of such
      fragmentations. It is logical that these DNA or RNA fragments must come from the
      genomes or the genes essential for the proliferation or cell division. The
      symbiotic and parasitic interrelationships of bacteria, plants and animals make
      the problem more complex and confusing, because all of them thrive and grow in
      each other cells, thus producing more nucleoproteins of each. Virions contain a
      small quantum of energy as the initial source of bioenergy to ignite and initiate
      the complex chemical reactions needed to use the potential energy reservoirs from
      the host. In this respect viruses can be considered as borderline between the
      living and the non-living. If one has to develop an effective drug or method for
      treating virus infections or cancers, the drug must have an antimitotic activity
      without affecting other normal functions. Such seems to be the case of globin
      derivatives of sickle cell and thalassemia red blood cells.

PMID- 8875806
TI  - Pump it up. A new implant sustains heart patients waiting for transplants.

PMID- 8875805
TI  - The effect of mefloquine and quinine on the relaxation times of water protons in
      human erythrocytes, as revealed by NMR.
AB  - Effects of mefloquine and quinine on human erythrocyte membranes were
      investigated by 1H-NMR spectroscopy. The observed spin-spin relaxation time (T2)
      of intracellular water protons was found to reflect water permeability of the
      membrane. The effects of these drug treatments on the erythrocytes were
      determined by the ratio of the T2 of control and experimental samples. Comparing
      the results of quinine and mefloquine treatments, quinine decreased the T2 ratio
      to 0.79 at 5 mM and mefloquine increased the ratio to 1.14 at 0.5 mM. These
      results demonstrated that quinine increases water permeability through the
      membranes whereas mefloquine decreases it.

PMID- 8875807
TI  - Profile: Thereza Imanishi-Kari.

PMID- 8875808
TI  - Immunity and the invertebrates.

PMID- 8875809
TI  - Sharks and the origins of vertebrate immunity.

PMID- 8875810
TI  - Dyslexia.

PMID- 8875811
TI  - Three-dimensional distortion correction applied to tomographic reconstructions of
      sectioned crystals.
AB  - Unaveraged tomograms of embedded and sectioned insect flight muscle show not only
      structural variation within the individual unit cells but also defects in the
      filament lattice such as lack of straightness of the filaments and wrinkling of
      the sections. Adaptation of conventional 2D crystal image processing methods
      usually average out these structural variations and lattice defects thereby
      reducing the resolution and information content of the 3D reconstructions. We
      present here a computational method to correct the reconstructed 3D object for
      these distortions to make it suitable for further analysis. The correction is an
      extension of conventional 2D cross-correlation techniques applied to a 3D image.
      These procedures determine the unit cell positions of the distorted crystal and
      use a spline-fitting approach to calculate a mapping function from the observed
      positions that is subsequently used to reinterpolate the image onto a regular
      grid. The resulting reinterpolated image is corrected for both filament
      straightening as well as section wrinkling.

PMID- 8875813
TI  - Planned Activities Training for mothers of children with developmental
      disabilities. Community generalization and follow-up.
AB  - Planned Activities Training (PAT) teaches mothers to plan and structure
      activities to prevent challenging child behaviors. PAT was evaluated with four
      mothers of children with developmental disabilities, including autism, Down
      Syndrome, and ADHD. PAT was used independent of any other behavior management
      techniques to examine its impact on mother and child behaviors, which were
      examined in addition to "fidelity" data on the mothers' implementation of PAT
      techniques. A multiple probe experimental design across two families with a
      replication across two more families demonstrated that PAT produced marked
      improvements in mother and child behavior in three generalization settings. In
      most cases, mothers' use of PAT procedures more than doubled. Three mothers'
      appropriate behavior increased from 25% to 40%. Improvements in child behavior
      ranged from 20% to more than 50%. Intervention gains were maintained at 1, 3, and
      6 months. These results suggest that PAT is a useful technique for promoting
      durable generalization of mother child skills.

PMID- 8875812
TI  - Violent assault, posttraumatic stress disorder, and depression. Risk factors for
      cigarette use among adult women.
AB  - Cigarette smoking may be conceptualized as a strategy to cope with negative
      affect. Therefore, rates of cigarette use might be expected to be greater in
      individuals experiencing events that produce negative affect, such as assault. To
      test this hypothesis, a national sample of 3,006 women aged 18 and older was
      assessed for lifetime and current cigarette use, previous history of physical and
      sexual assault, lifetime and current incidence of depression, and lifetime and
      current incidence of PTSD. Results indicated that the odds of active smoking in
      women with a lifetime history of assault were 1.82 times those of women with no
      previous history of assault. Similarly, risk of active cigarette use in women
      with a previous history of depression or PTSD was 2.22 and 1.34 times those of
      women with no depressive or PTSD history, respectively. Recent assault, current
      PTSD, or current depression status were not associated with increased cigarette
      use.

PMID- 8875814
TI  - Methylphenidate and attentional training. Comparative effects on behavior and
      neurocognitive performance in twin girls with attention-deficit/hyperactivity
      disorder.
AB  - The effectiveness of four doses (5-mg, 10-mg, 15-mg, 20-mg) of methylphenidate
      (MPH) and attentional training (AT) were evaluated using neurocognitive
      instruments (Continuous Performance Test; Matching Unfamiliar Figures Test),
      narrow- and broad-band rating scales in the context of a double-blind, placebo
      control, within-subject reversal design for dizygotic twin girls with Attention
      Deficit/Hyperactivity Disorder (ADHD). Both interventions proved effective for
      improving neurocognitive test performance and behavior, although broad-band
      ratings revealed dose-response curves different from those obtained from the
      neurocognitive tests. Implications for clinical management of girls with ADHD are
      discussed.

PMID- 8875815
TI  - Acquisition and functional use of voice output communication by persons with
      profound multiple disabilities.
AB  - The acquisition and subsequent functional use of communication skills by persons
      with profound mental and physical impairment using a voice output communication
      aid (VOCA) was evaluated. Initially, a graduated guidance and time delay
      procedure was used to teach three individuals to use a VOCA in response to a
      trainer's specific request. Results indicated that all participants increased
      their correct VOCA activations in response to specific requests following
      training. Probes also indicated that participants effectively used the VOCA after
      training to request preferred items in a variety of settings. The functional
      utility of VOCA skills was supported by a survey of individuals unfamiliar with
      the participants. This survey indicated that those surveyed could better
      understand the participants when they used a VOCA. Results are discussed as to
      potential advantages of VOCAs relative to other augmentative communication
      options for persons with multiple disabilities. Future research directions are
      discussed, focusing on strategies for promoting a broader set of communicative
      interactions using VOCAs.

PMID- 8875816
TI  - A biobehavioral approach toward managing encopresis.
AB  - The purpose of this study was to evaluate the effectiveness of a biobehavioral
      treatment approach for two encopretic children. Both subjects were evaluated and
      treated by a pediatric gastroenterologist, with behavioral interventions
      occurring subsequent to, and in conjunction with, the medical intervention.
      Results showed that the biobehavioral approach resulted in significant
      improvements for both subjects, and that the use of response cost may be a
      necessary intervention component for some children. A model is also presented to
      clarify the relationship between organic and nonorganic factors and their
      relationship to encopresis.

PMID- 8875817
TI  - On volume changes accompanying conformational transitions of biopolymers.

PMID- 8875818
TI  - Elastin dehydration through the liquid and the vapor phase: a comparison of
      osmotic stress models.
AB  - The swelling and viscoelastic behaviors of samples of purified arterial elastin
      were investigated to develop a model for studying the viscoelastic behavior of
      elastin. Two osmotic stress models were used: the vapor phase model (VPM), in
      which the stress on the elastin sample was applied through the vapor phase by
      equilibrating the sample over a saline solution, and the liquid phase model
      (LPM), in which the stress was applied through the liquid phase by equilibrating
      the sample in aqueous solutions of large molecular weight polymers. The elastin
      in the VPM showed a highly varied viscoelastic response, and was slightly stiffer
      and had a slightly higher damping coefficient than the elastin in the LPM at
      equivalent nominal relative humidities. We believe the difference in behavior of
      the elastin in the two models was due to geometric distortions of the elastin
      that occur during dehydration in the VPM. In the LPM, the spaces between the
      elastin fibrils are filled with water, and in the VPM these spaces collapse when
      the water is removed. Removal of only the interfibrillar water deswelled the
      tissue and increased its stiffness and damping coefficient. Viscoelastic spectra
      obtained at different levels of osmotic stress in the LPM were reducible to one
      master curve, indicating that the dominant effect of dehydration is a nonspecific
      reduction of molecular mobility. We conclude that the LPM is a better model than
      the VPM for studying the effects of dehydration on the mechanical behavior of
      elastin.

PMID- 8875819
TI  - Swelling and viscoelastic properties of osmotically stressed elastin.
AB  - The swelling and viscoelastic properties of purified elastin were studied in
      aqueous solutions of superswelling agents or osmotic deswelling agents to develop
      models to study the behavior of elastin at frequencies not easily accessible by
      direct measurement. Increasing the concentration of any of the deswelling solutes
      (glucose, sucrose, sodium chloride, ammonium sulphate, dextran, and polyethylene
      glycol) increased the tensile storage and loss moduli. The viscoelastic behavior
      was independent of solute when compared on the basis of swelling behavior. The
      data collected at various solute concentrations at 37 degrees C could be reduced
      to one master curve, and the master curves for elastin in each of the deswelling
      solutes were themselves superposable. The ability to reduce the data indicates
      that dehydration can be used to model elastin's viscoelastic behavior at high
      frequencies or over short times. The viscoelastic behavior of elastin in the
      superswelling agents [potassium thiocyanate (KSCN), dimethyl sulfoxide (DMSO),
      and ethylene glycol (EG)] depended on the solute and was independent of swelling
      behavior. In KSCN the behavior of elastin seemed to be a continuation of the
      pattern established by the deswelling agents in that an increase in swelling was
      accompanied by a decrease in both moduli, and the viscoelastic spectra were
      reducible to one master curve. In high concentrations of DMSO and EG the spectra
      were not reducible. KSCN appears a suitable superswelling solute to model
      elastin's viscoelastic behavior at low frequencies or over long times.

PMID- 8875821
TI  - Monte Carlo simulation of multiple attack mechanism of alpha-amylase.
AB  - Porcine pancreatic alpha-amylase (EC 3.2.1.1) produces short
      maltooligosaccharides from a single enzyme-substrate complex without dissociation
      by multiple or repetitive attack. Multiple attack is caused by relative sliding
      of the enzyme along the product chain of the enzyme-product complex without
      dissociation to form another productive complex. The Monte Carlo method was
      applied to the multiple attack mechanism to predict product distribution from
      amylose and amylopectin molecules of arbitrary sizes. The position of the initial
      attack to make the enzyme-substrate complex and branched reaction paths from the
      enzyme-product complex were selected by random numbers and probabilities. A
      simulated product distribution from 100,000 samples of amylose of chain length
      greater than 80 agreed completely with experimental data at the early stage of
      hydrolysis of amylose of mean chain length 90. On the other hand, the simulated
      product distribution from amylopectin agreed with experimental data of potato
      amylopectin when the effective chain length of the A chain was 9. Since the mean
      chain length of the A chain of potato amylopectin is 15, it is possible that
      amylopectin is partially compact in solution, so that the enzyme can recognize
      and act only on the outer side of the A chain at the early stage of digestion.

PMID- 8875820
TI  - CD and NMR structural characterization of ceratotoxins, natural peptides with
      antimicrobial activity.
AB  - Antibacterial properties of the secretion from the female reproductive accessory
      glands of medfly Ceratitis capitata are mostly ascribed to the presence of two
      peptides, ceratotoxin A and B, which exhibit a strong activity against gram
      positive and gram-negative bacterial strains, and show sequence and function
      homology with cecropins, melittin, and magainins. CD experiments performed in
      different solvents indicate the presence of a significant content of helical
      structures in organic solvent. Two-dimensional nmr results for ceratotoxin A in
      methanol show a helical behavior for the 8-25 region of the peptide. A
      ramachandran classification of each residue for the structures obtained from
      distance geometry calculations lead to the definition of four structural families
      in which the central segment 10-19 is always helical and differences refer to
      residues 8-9 and 19-23. A sequence analysis of the two ceratotoxins and a
      systematic search on the protein data bank revealed the occurrence of a KX
      hydrophobic-hydrophobic-P motif that seems to be important for helix
      stabilization.

PMID- 8875823
TI  - Use of graph theory for secondary structure recognition and sequential assignment
      in heteronuclear (13C, 15N) NMR spectra: application to HU protein from Bacillus
      stearothermophilus.
AB  - A computer-assisted procedure, based upon a branch of mathematics known as graph
      theory, has been developed to recognize secondary structure elements in proteins
      from their corresponding nuclear Overhauser effect spectroscopy (NOESY)-type
      spectra and to carry out their sequential assignment. In the method, NOE
      connectivity templates characteristic of regular secondary structures are
      identified in the spectra. Resonance assignment is then achieved by connecting
      these NOE patterns of secondary structure together, and thereby matching
      connected spin systems to specific parts of the primary sequence. The range of
      NOE-graph templates of secondary structure motifs, incorporating alpha-helices
      and beta-strand motifs, has been examined for reliability and extent of secondary
      structure identification in a data base composed of the high resolution
      structures of 20 proteins. The analysis identified several robust NOE-graph
      templates and supports the implementation of an ordered search strategy. The
      method, known as SERENDIPITY, has been applied to the analysis of nuclear
      Overhauser effect data from a three-dimensional time-shared nuclear Overhauser
      effect spectroscopy (13C, 15N) heteronuclear single quantum correlation spectrum
      of the (alpha + beta) type protein HU from Bacillus stearothermophilus. The
      arrangement of the elucidated elements of secondary structure is very similar to
      that of the x-ray and nmr structures of HU. In addition, our analysis revealed a
      pattern of interstrand nuclear Overhauser effect in the beta-arm region (residues
      53-76) of HU, which suggest irregularities, not reported in the x-ray structure,
      in both strands of the beta-arm at Ala57 and Pro72, respectively. At these
      residues, both strands of the beta-arm appear to flip inside out before
      continuing as a regular antiparallel beta-sheet.

PMID- 8875824
TI  - Physicochemical studies on xylinan (acetan). I. Characterization by gel
      permeation chromatography on sepharose Cl-2B coupled with static light scattering
      and viscometry.
AB  - Laboratory-made samples of the polysaccharide xylinan (acetan) were fractionated
      on Sepharose Cl-2B using 0.1M NaCl as eluant. The weight average molar masses and
      intrinsic viscosities were estimated in the fractions by multiangle laser light
      scattering (off-line) and capillary viscometry, respectively. The Mark-Houwink
      Sakurada plot was found to be indicative of semiflexible coils (a = 0.90). The
      angular dependence of scattered light was interpreted by fitting with
      theoretically calculated "Master Curves" in terms of a wormlike chain model. The
      ambiguity of the interpretation of scattering curves owing to the overlapping
      effects of chain stiffness and polydispersity is discussed in detail. The
      experimental data is found to be consistent with a persistence length of Lp = 100
      nm. The main proportion consists of double-stranded chains (consistent with a
      robust double-helix), but single- and multistranded chains also are present. Our
      results suggest a fractionation according to the contour length rather than the
      molar mass.

PMID- 8875828
TI  - Is daily mortality associated specifically with fine particles?
AB  - Recent epidemiologic studies have consistently reported increased daily mortality
      associated with exposures to particulate air pollution. Currently, particulate
      mass is measured as particles smaller than 10 microns (PM10). Fine (PM2.5) and
      coarse (PM10-PM2.5) mass and sulfate particle concentrations were measured in six
      eastern U.S. cities for eight years, and aerosol acidity concentrations were
      measured for approximately one year. Daily mortality for these metropolitan areas
      was combined with particulate air pollution and weather measurements. City
      specific associations with each measure of particle pollution were estimated by
      Poisson regression, adjusting for time trends and weather by nonparametric
      methods. Combined effect estimates were calculated as the inverse variance
      weighted mean of the city-specific estimates. PM10, PM2.5, and SO4= were each
      significantly associated with increased daily mortality, while no associations
      were found with coarse mass nor with aerosol acidity (H+) concentrations. The
      strongest association was found with PM2.5. A 10 micrograms/m3 increase in two
      day mean PM2.5 was associated with a 1.5% (95% CI 1.1% to 1.9%) increase in total
      daily mortality. Somewhat larger increases were found for deaths caused by
      chronic obstructive pulmonary disease (+3.3%) and by ischemic heart disease
      (+2.1%). These data suggest that increased daily mortality is specifically
      associated with particle mass constituents found in the aerodynamic diameter size
      range under 2.5 microns, that is, with combustion-related particles.

PMID- 8875830
TI  - Annual variation of insecticides in precipitation in rural Japan.

PMID- 8875831
TI  - Organophosphate Flame Retardants in Needles of Pinus ponderosa in the Sierra
      Nevada Foothills

PMID- 8875832
TI  - N-nitroso compounds in the ambient air of metal factories using metal-working
      fluids.

PMID- 8875833
TI  - Mechanism of chromium detoxification in Pseudomonas fluorescens is dependent on
      iron.

PMID- 8875835
TI  - Liming, reacidification, and the mobilization of cadmium from sediments.

PMID- 8875834
TI  - Identification of final biodegradation product of nonylphenol ethoxylate (NPE) by
      river microbial consortia.

PMID- 8875836
TI  - Feminization of male common tern embryos is not correlated with exposure to
      specific PCB congeners.

PMID- 8875837
TI  - Effects of methyl parathion on reproduction in the Japanese quail.

PMID- 8875838
TI  - Accumulation of chlordanes in adipose tissues of mice caused by long-term
      exposure of low level technical chlordane.

PMID- 8875839
TI  - Metal Uptake by Agricultural Plant Species Grown in Sludge-Amended Soil Following
      Ecosystem Restoration Practices

PMID- 8875840
TI  - Effects of Nematicides on Pratylenchus penetrans, Soil Nitrification, and Growth
      of Flue-Cured Tobacco

PMID- 8875841
TI  - Distribution of lead, cadmium, and zinc in tissues of hens and chickens from
      Slovenia.

PMID- 8875842
TI  - Comparison of the pesticide capture efficiency of potential passive dosimeter
      materials.

PMID- 8875843
TI  - Semiquantitative evaluation of dermal exposure to granulated insecticides in
      coffee (Coffea arabica L.) crop and efficiency of individual protective
      equipment.

PMID- 8875844
TI  - Lead content in human scalp hair of rural and urban residents in Taiwan.

PMID- 8875846
TI  - Metal Bioaccumulation by Sea Urchin (Echinometra mathaei) from the Saudi Coastal
      Areas of the Arabian Gulf: 2. Cadmium, Copper, Chromium, Barium, Calcium, and
      Strontium

PMID- 8875845
TI  - Metal contents in the tissues of Lutjanus fulviflamma (Smith 1949) and
      Epinephelus tauvina (Forskal 1775) collected from the Arabian Gulf.

PMID- 8875847
TI  - Effects of monosodium glutamate wastewater on the fish Ctenopharyngodon idellus
      and the cabbage Brassica capestris.

PMID- 8875848
TI  - Acetylcholinesterase activity in juveniles of Daphnia magna Straus.

PMID- 8875849
TI  - Chlorella vulgaris Growth on Pretreated Cane Sugar Mill Waste

PMID- 8875850
TI  - Bioconcentration and Uptake of a Pyrethroid and Organophosphate Insecticide by
      Selected Aquatic Insects

PMID- 8875852
TI  - Response of Lemna minor to Sodium Chloride and a Statistical Analysis of
      Continuous Measurements for EC50 and 95% Confidence Limits Calculation

PMID- 8875851
TI  - Toxic effects of synthetic pyrethroids on Cyprinus carpio Linn. eggs.

PMID- 8875853
TI  - Influence of poultry litter on the toxicity of cadmium to aquatic organisms.

PMID- 8875854
TI  - Chiral symmetry breaking during the self-assembly of monolayers from achiral
      purine molecules.
AB  - Scanning tunneling microscopy was used to investigate the structure of the two
      dimensional adsorbate formed by molecular self-assembly of the purine base,
      adenine, on the surfaces of the naturally occurring mineral molybdenite and the
      synthetic crystal highly oriented pyrolytic graphite. Although formed from
      adenine, which is achiral, the observed adsorbate surface structures were
      enantiomorphic on molybdenite. This phenomenon suggests a mechanism for the
      introduction of a localized chiral symmetry break by the spontaneous
      crystallization of these prebiotically available molecules on inorganic surfaces
      and may have some role in the origin of biomolecular optical asymmetry. The
      possibility that purine-pyrimidine arrays assembled on naturally occurring
      mineral surfaces might act as possible templates for biomolecular assembly is
      discussed.

PMID- 8875855
TI  - Divalent cations modify adsorption of 5'-AMP onto precipitated calcium phosphate:
      a model for cation modulation of adsorptive processes in primitive aqueous
      environments.
AB  - The adsorption of 5'-AMP onto precipitated calcium phosphate (CaPi) requires the
      presence of soluble calcium and this dependence exhibits a Michaelian-like
      behavior. This result suggests that the formation of a complex between 5'-AMP and
      free Ca2+ (CaAMP) is a prelude to the adsorption of the nucleotide in the solid
      matrix. At concentrations one order of magnitude higher, Mn2+ and Mg2+ can
      substitute for soluble Ca2+ in the adsorption of 5'-AMP onto solid CaPi. However,
      when added simultaneously with 5'-AMP to a heterogeneous mixture that contains
      CaPi and soluble Ca2+, Mn2+ and Mg2+ inhibit the adsorption of 5'-AMP in a
      concentration-dependent manner. This suggests the formation of complexes that are
      much less effective for 5'-AMP adsorption than the CaAMP complex. On the other
      hand, Mn2+ and Mg2+ cannot promote desorption of the nucleotide attached to the
      precipitate in the presence of soluble Ca2+ if they are added after adsorption
      has attained equilibrium. Although desorption of 5'-AMP can be obtained by a
      sequential dilution of the soluble phase with buffer and no nucleotide in a
      process that obeys a Langmuir equation, the lack of effect of Mn2+ or Mg2+ when
      adsorption has attained its maximal value suggests strong interactions between
      the CaAMP complex and the solid matrix when adsorption equilibrium is reached.
      The divalent cations present in the matrix also participate with different
      selectivity in the attachment of the CaAMP complex, indicating that a cation
      exchange mechanism could have acted in the modulation of adsorptive/desorptive
      processes involving biomonomers and phosphate surfaces in primitive aqueous
      environments.

PMID- 8875856
TI  - The mitochondrial DNA molecule of Sumatran orangutan and a molecular proposal for
      two (Bornean and Sumatran) species of orangutan.
AB  - The complete mitochondrial DNA (mtDNA) molecule of Sumatran orangutan, plus the
      complete mitochondrial control region of another Sumatran specimen and the
      control regions and five protein-coding genes of two specimens of Bornean
      orangutan were sequenced and compared with a previously reported complete mtDNA
      of Bornean orangutan. The two orangutans are presently separated at the
      subspecies level. Comparison with five different species pairs-namely, harbor
      seal/grey seal, horse/donkey, fin whale/blue whale, common chimpanzee/pygmy
      chimpanzee, and Homo/common chimpanzee-showed that the molecular difference
      between Sumatran and Bornean orangutan is much greater than that between the
      seals, and greater than that between the two chimpanzees, but similar to that
      between the horse and the donkey and the fin and blue whales. Considering their
      limited morphological distinction the comparison revealed unexpectedly great
      molecular difference between the two orangutans. The nucleotide difference
      between the orangutans is about 75% of that between Homo and the common
      chimpanzee, whereas the amino acid difference exceeds that between Homo and the
      common chimpanzee. On the basis of their molecular distinction we propose that
      the two orangutans should be recognized as different species, Pongo pygmaeus,
      Bornean orangutan, and P. abelii, Sumatran orangutan.

PMID- 8875858
TI  - Evolution of the nad3-rps12 gene cluster in angiosperm mitochondria: comparison
      of edited and unedited sequences.
AB  - We have analyzed the nad3-rps12 locus for eight angiosperms in order to compare
      the utility of mitochondrial DNA and edited mRNA sequences in phylogenetic
      reconstruction. The two coding regions, containing from 25 to 35 editing sites in
      the various plants, have been concatenated in order to increase the significance
      of the analysis. Differing from the corresponding chloroplast sequences, unedited
      mitochondrial DNA sequences seem to evolve under a quasi-neutral substitution
      process which undifferentiates the nucleotide substitution rates for the three
      codon positions. By using complete gene sequences (all codon positions) we found
      that genomic sequences provide a classical angiosperm phylogenetic tree with a
      clear-cut grouping of monocotyledons and dicotyledons with Magnoliidae at the
      basal branch of the tree. Conversely, owing to their low nucleotide substitution
      rates, edited mRNA sequences were found not to be suitable for studying
      phylogenetic relationships among angiosperms.

PMID- 8875857
TI  - The complete mitochondrial DNA (mtDNA) of the donkey and mtDNA comparisons among
      four closely related mammalian species-pairs.
AB  - The nucleotide sequence of the complete mitochondrial genome of the donkey, Equus
      asinus, was determined. The length of the molecule is 16,670 bp. The length,
      however, is not absolute due to pronounced heteroplasmy caused by variable
      numbers of two types of repetitive motifs in the control region. The sequence of
      the repeats is (a) 5'-CACACCCA and (b) 5'-TGCGCGCA, respectively. The order of
      (a) and (b) can be expressed as {n[2(a)+(b)]+m(a)}. In 32 different clones
      analyzed the number of n and m ranged from 0 to 9 and 1 to 7. The two rRNA genes,
      the 13 peptide-coding genes, and the 22 tRNA genes of the donkey and the horse,
      Equus caballus, were compared in detail. Total nucleotide difference outside the
      control region was 6.9%. Nucleotide difference between peptide-coding genes
      ranged from 6.4% to 9.4% with a mean of 8.0%. In the inferred protein sequences
      of the 13 peptide-coding genes the amino acid difference was 0.2-8.8%, and the
      mean for the 13 concatenated amino acid sequences was 1.9%. In the 22 tRNA genes,
      the mean difference was 3.5%, and that in the two rRNA genes was 4.1%. The mtDNA
      differences between the donkey and the horse suggest that the evolutionary
      separation of the two species occurred approximately 9 million years ago.
      Analyses of differences among the mtDNAs of three other species-pairs, harbor
      seal/grey seal, fin whale/blue whale, and Homo/common chimpanzee, showed that the
      relative evolutionary rate of individual peptide-coding genes varies among
      different species-pairs and modes of comparison. The findings show that the
      superimposition of sequence data of one lineage for resolving and dating
      evolutionary divergences of other lineages should be performed with caution
      unless based on comprehensive data.

PMID- 8875859
TI  - Transkingdom transfer of the phosphoglucose isomerase gene.
AB  - Previous analysis of the gene encoding phosphoglucose isomerase (Pgi) suggests
      that this gene may have been transferred between a eukaryote and a bacterium.
      However, excluding the alternative hypothesis of ancient gene duplication has
      proven difficult because of both insufficient sampling of taxa and an earlier
      misidentification of a bacterial Pgi sequence. This paper presents a phylogenetic
      analysis of published complete Pgi sequences together with analysis of new
      partial Pgi sequences from six species of bacteria. The data identify a group of
      bacterial Pgi sequences, including sequences from Escherichia coli and
      Haemophilus influenzae, which are more closely related to eukaryotic Pgi
      sequences than to other bacterial sequences. The topology of gene trees
      constructed using several different methods are all consistent with the
      hypothesis of lateral gene transfer and not ancient gene duplication.
      Furthermore, an estimate of a molecular clock for Pgi dates the divergence of the
      E. coli and H. influenzae sequences from the animal sequences to between 470 and
      650 million years ago, well after other estimates of the divergence between
      eukaryotes and bacteria. This study provides the most convincing evidence to date
      of the transkingdom transfer of a nuclear gene.

PMID- 8875860
TI  - Structural analysis of the rDNA intergenic spacer of Brassica nigra: evolutionary
      divergence of the spacers of the three diploid Brassica species.
AB  - EcoRI restriction of the B. nigra rDNA recombinants, isolated from a lambda
      genomic library, showed that the 3.9-kb fragment corresponded to the Intergenic
      Spacer (IGS), which was sequenced and found to be 3,928 bp in size. Sequence and
      dot-matrix analyses showed that the organization of the B. nigra rDNA IGS was
      typical of most rDNA spacers, consisting of a central repetitive region and
      flanking unique sequences on either side. The repetitive region was composed of
      two repeat families-RF 'A' and RF 'B.' The B. nigra RF 'A' consisted of a tandem
      array of three full-length copies of a 106-bp sequence element. RF 'B' was
      composed of 66 tandemly repeated elements. Each 'B' element was only 21-bp in
      size and this is the smallest repeat unit identified in plant rDNA to date. The
      putative transcription initiation site (TIS) was identified as nucleotide
      position 3,110. Based on the sequence analysis it was suggested that the present
      organization of the repeat families was generated by successive cycles of
      deletions and amplifications and was being maintained by homogenization processes
      such as gene conversion and crossing-over.A detailed comparison of the rDNA IGS
      sequences of the three diploid Brassica species-namely, B. nigra, B. campestris,
      and B. oleracea-was carried out. First, comparisons revealed that B. campestris
      and B. oleracea were close to each other as the repeat families in both showed
      high sequence homology between each other. Second, the repeat elements in both
      the species were organized in an interspersed manner. Third, a 52-bp sequence,
      present just downstream of the repeats in B. campestris, was found to be
      identical to the B. oleracea repeats, thereby suggesting a common progenitor. On
      the other hand, in B. nigra no interspersion pattern of organization of repeats
      was observed. Further, the B. nigra RF 'A' was identified as distinct from the
      repeat families of B. campestris and B. oleracea. Based on this analysis, it was
      suggested that during speciation B. campestris and B. oleracea evolved in one
      lineage whereas B. nigra diverged into a separate lineage. The comparative
      analysis of the IGS helped in identifying not only conserved ancestral sequence
      motifs of possible functional significance such as promoters and enhancers, but
      also sequences which showed variation between the three diploid species and were
      therefore identified as species-specific sequences.

PMID- 8875861
TI  - Nucleotide sequence and presumed secondary structure of the 28S rRNA of pea
      aphid: implication for diversification of insect rRNA.
AB  - Determination of the entire nucleotide sequence of the aphid 28S ribosomal RNA
      gene (28S rDNA) revealed that it is 4,147 bp in length with a G + C content of
      60.3%. Based on the nucleotide sequence, we constructed a presumed secondary
      structure model of the aphid 28S rRNA which indicated that the aphid 28S rRNA is
      characterized by the length and high G + C content of its variable regions. The G
      + C content of the aphid's variable regions was much higher than that of the
      entire sequence of the 28S rRNA, which formed a striking contrast to those of
      Drosophila with the G + C content much lower than the entire 28S molecule. In
      this respect, the aphid 28S rRNA somewhat resembled those of vertebrates. This is
      the third report of a complete large-subunit rRNA sequence from an arthropod, and
      the first 28S rRNA sequence for a nondipterous insect.

PMID- 8875862
TI  - Large-subunit rRNA sequence of the chytridiomycete Blastocladiella emersonii, and
      implications for the evolution of zoosporic fungi.
AB  - The 5.8S and 28S ribosomal RNA sequences of the chytridiomycete Blastocladiella
      emersonii were determined. These data were combined with 18S rRNA sequences in
      order to carry out a phylogenetic analysis based on distance matrix, parsimony,
      and maximum likelihood methods. The new data confirmed that chytridiomycetes are
      true fungi and not protists, as was already suggested on the basis of
      biochemical, ultrastructural, and 18S rRNA data. Within the fungal clade, B.
      emersonii formed the first line of divergence. The position of the fungi within
      the eukaryotic "crown" taxa was also reassessed, and the alveolate-stramenopile
      cluster appeared as their sister group. The stramenopiles also comprise a number
      of zoosporic fungi, which resemble chytridiomycetes in so many respects, e.g.,
      production of motile spores, thallus morphology, and absorptive nutrition, that
      they have been classified together with them in the past. This suggests that the
      possible common ancestor of the fungi, stramenopiles, and alveolates may have
      been a zoosporic fungus, which would mean that zoosporic fungi are paraphyletic
      instead of polyphyletic as previously suggested.

PMID- 8875864
TI  - Phylogenetic analysis of Veneridae (Bivalvia): comparison of molecular and
      palaeontological data.
AB  - An approximately 400-bp-long portion of the 16s rRNA gene sequence has been
      determined for the venerid clams Chamelea gallina (Chioninae), Dosinia lupinus
      (Dosiniinae), Pitar rudis, Callista chione (Pitarinae), Tapes decussatus, T.
      philippinarum, Venerupis (= Paphia) aurea (Tapetinae), and Venus verrucosa
      (Venerinae). Neighbor-joining and maximum parsimony trees support the results of
      traditional classification methods at the subfamily level but do not support the
      concept of a genus Tapes. The transversion divergence rate estimated on the basis
      of the palaeontological record for the C. gallina/V. verrucosa separation and for
      the Pitarinae is very close (0.14-0.16% per Myr, respectively) to that of
      ungulates and cetaceans, while the Tapetinae exhibit a much higher (0.36% per
      Myr) rate.

PMID- 8875865
TI  - The ruminant digestion model using bacteria already employed early in evolution
      by symbiotic molluscs.
AB  - The purification and some molecular properties of six lysozymes from the gills of
      different mytilids and vesicomyids are described: they belong to the previously
      described Invertebrate lysozyme family. The predominance of the bacterial
      nutrition in these organisms seems to necessitate the presence of a lysozyme as
      in the case of the ruminant digestion model.

PMID- 8875863
TI  - Classification and phylogeny of the MADS-box multigene family suggest defined
      roles of MADS-box gene subfamilies in the morphological evolution of eukaryotes.
AB  - The MADS-box encodes a novel type of DNA-binding domain found so far in a diverse
      group of transcription factors from yeast, animals, and seed plants. Here, our
      first aim was to evaluate the primary structure of the MADS-box. Compilation of
      the 107 currently available MADS-domain sequences resulted in a signature which
      can strictly discriminate between genes possessing or lacking a MADS-domain and
      allowed a classification of MADS-domain proteins into several distinct
      subfamilies. A comprehensive phylogenetic analysis of known eukaryotic MADS-box
      genes, which is the first comprising animal as well as fungal and plant homologs,
      showed that the vast majority of subfamily members appear on distinct subtrees of
      phylogenetic trees, suggesting that subfamilies represent monophyletic gene
      clades and providing the proposed classification scheme with a sound evolutionary
      basis. A reconstruction of the history of the MADS-box gene subfamilies based on
      the taxonomic distribution of contemporary subfamily members revealed that each
      subfamily comprises highly conserved putative orthologs and recent paralogs. Some
      subfamilies must be very old (1,000 MY or more), while others are more recent. In
      general, subfamily members tend to share highly similar sequences, expression
      patterns, and related functions. The defined species distribution, specific
      function, and strong evolutionary conservation of the members of most subfamilies
      suggest that the establishment of different subfamilies was followed by rapid
      fixation and was thus highly advantageous during eukaryotic evolution. These gene
      subfamilies may have been essential prerequisites for the establishment of
      several complex eukaryotic body structures, such as muscles in animals and
      certain reproductive structures in higher plants, and of some signal transduction
      pathways. Phylogenetic trees indicate that after establishment of different
      subfamilies, additional gene duplications led to a further increase in the number
      of MADS-box genes. However, several molecular mechanisms of MADS-box gene
      diversification were used to a quite different extent during animal and plant
      evolution. Known plant MADS-domain sequences diverged much faster than those of
      animals, and gene duplication and sequence diversification were extensively used
      for the creation of new genes during plant evolution, resulting in a relatively
      large number of interacting genes. In contrast, the available data on animal
      genes suggest that increase in gene number was only moderate in the lineage
      leading to mammals, but in the case of MEF2-like gene products,
      heterodimerization between different splice variants may have increased the
      combinatorial possibilities of interactions considerably. These observations
      demonstrate that in metazoan and plant evolution, increased combinatorial
      possibilities of MADS-box gene product interactions correlated with the evolution
      of increasingly complex body plans.

PMID- 8875866
TI  - The primary structure of a chondrichthyan protamine: a new apparent contradiction
      in protamine evolution.
AB  - We have determined the primary structure of protamine R3 from ratfish (Hydrolagus
      colliei), a species belonging to the order Chimaeriformes (an old phylogenetic
      line among the chondrichthyes). Protamine R3 contains 48 residues organized as
      follows: ARRRH SMKKK RKSVR RRKTR KNQRK RKNSL GRSFK (Q/A)HGFL KQPPR FRP.
      Comparison of this sequence with both protamine Z3 from Scyliorhinus canicula (a
      chondrichthyan) and typical protamines from bony fish generates an apparent
      contradiction: Two relatively close species (H. colliei and S. canicula, both
      chondichthyes) display different protamines, whereas species more distant in
      evolution (S. canicula and bony fish) contain very similar protamine molecules.
      We note that this is not an isolated case in the evolution of sperm nuclear basic
      proteins (SNBPs) and discuss the possible significance of this fact.

PMID- 8875867
TI  - A modular domain of NifU, a nitrogen fixation cluster protein, is highly
      conserved in evolution.
AB  - hnifU, a gene exhibiting similarity to nifU genes of nitrogen fixation gene
      clusters, was identified in the course of expressed sequence tag (EST) generation
      from a human fetal heart cDNA library. Northern blot of human tissues and
      polymerase chain reaction (PCR) using human genomic DNA verified that the hnifU
      gene represented a human gene rather than a microbial contaminant of the cDNA
      library. Conceptual translation of the hnifU cDNA yielded a protein product
      bearing 77% and 70% amino acid identity to NifU-like hypothetical proteins from
      Haemophilus influenzae and Saccharomyces cerevisiae, respectively, and 40-44%
      identity to the N-terminal regions of NifU proteins from several diazatrophs
      (i.e., nitrogen-fixing organisms). Pairwise determination of amino acid
      identities between the NifU-like proteins of nondiazatrophs showed that these
      NifU-like proteins exhibited higher sequence identity to each other (63-77%) than
      to the diazatrophic NifU proteins (40-48%). Further, the NifU-like proteins of
      non-nitrogen-fixing organisms were similar only to the N-terminal region of
      diazatrophic NifU proteins and therefore identified a novel modular domain in
      these NifU proteins. These findings support the hypothesis that NifU is indeed a
      modular protein. The high degree of sequence similarity between NifU-like
      proteins from species as divergent as humans and H. influenzae suggests that
      these proteins perform some basic cellular function and may be among the most
      highly conserved proteins.

PMID- 8875868
TI  - Preoperative endosonographic staging of cancer of the cardia.
AB  - BACKGROUND: To evaluate the diagnostic accuracy of endosonography (ES) in a
      prospective series of cancer of the cardia. METHODS: Thirty-five patients with
      cancer of the cardia were investigated by ES; 29 underwent surgery. ES staging
      for the surgery patients was compared with histopathologic findings. Tumors were
      staged according to the 1987 TNM classification. RESULTS: ES had a diagnostic
      accuracy of 79% for the T category, 79% for the N category, 89% for the M
      category, and 72% for prognostic TNM staging. CONCLUSION: ES is an excellent
      paraclinical modality for the staging of local-regional spread of cancer of the
      cardia and a useful complement to computed tomography for evaluation of these
      tumors.

PMID- 8875869
TI  - Plain and gadolinium-DTPA-enhanced MR imaging of hepatocellular carcinoma treated
      with transarterial chemoembolization.
AB  - BACKGROUND: To assess unenhanced and gadolinium-enhanced magnetic resonance (MR)
      imaging patterns of hepatocellular carcinoma (HCC) treated with transarterial
      chemoembolization (TACE). METHODS: Thirty-two patients with 48 HCC lesions
      underwent MR imaging before and 15 days after TACE. Fifteen lesions were then
      surgically resected. The remaining 33 lesions were not removed and were followed
      up with MR imaging at 3, 6, 12, and 18 months after treatment. Spin echo (SE) T1-
      and T2-weighted and gadolinium-enhanced SE T1-weighted sequences were employed.
      Qualitative evaluation of signal intensity pattern of the treated lesions was
      performed in all cases. Histological evaluation and selective hepatic
      arteriography were considered the gold standard of the study for the 15 resected
      lesions and the 33 unresected lesions, respectively. RESULTS: On follow-up
      enhanced T1-weighted images of the 15 resected lesions, seven showed no area of
      enhancement corresponding to complete necrosis at histologic examination. The
      remaining eight resected lesions showed areas of enhancement; in six of these
      cases, viable tumor tissue was found at histology; in the other two lesions,
      histologic examination revealed the presence of complete tumor necrosis. In the
      group of resected lesions, T2-weighted images showed no pattern characteristic of
      necrosis. In 24 of 33 unresected lesions, loss of enhancement on follow-up
      enhanced T1-weighted images was a characteristic finding, which correlated to
      devascularization at arteriography. Of these 24 lesions, 17 were completely
      hypointense on follow-up T2-weighted images; the remaining seven showed small
      foci of hyperintensity. The other nine unresected lesions showed enhanced
      portions on follow-up enhanced T1-weighted images, which corresponded to
      hyperintense areas on T2-weighted images. These findings correlated to
      persistence of hypervascular areas at arteriography. CONCLUSION: Gadolinium
      enhanced T1-weighted MR imaging is a reliable method for evaluating the outcome
      of TACE treatment and is more accurate than unenhanced T2-weighted MR imaging.

PMID- 8875870
TI  - Preoperative assessment of the portal vein and hepatic artery in children with
      end-stage liver disease: is selective angiography still necessary?
AB  - BACKGROUND: Selective angiography involves increased risk for children and may
      cause vascular complications. The aim of this study was to determine whether
      selective angiography is still necessary for viewing the portal vein and hepatic
      artery. METHODS: Doppler ultrasound, abdominal aortography, and selective
      angiography were performed and interpreted independently in 62 children (median
      age = 1 year 3 months), with end-stage liver disease, who were candidates for
      orthotopic liver transplantation. RESULTS: Selective angiography agreed with the
      Doppler ultrasound findings of patency, flow direction, and diameter of the
      extrahepatic portal vein in 84%, 73%, and 79% of the children, respectively.
      Important additional information was obtained from selective angiography in only
      five of the 62 children (8%). Selective angiography showed an anomaly of the
      hepatic artery in 21 of the 62 children (33%). In 18 out of these 21 children
      (85%), an anomaly of the hepatic artery was already visible on the abdominal
      aortogram. CONCLUSION: Selective angiography did not play any significant role in
      the detection of an anomaly of the hepatic artery and should only be done if the
      Doppler ultrasound findings of the portal vein are inconclusive or if abdominal
      aortography cannot provide reliable information about the hepatic artery. For the
      evaluation of the portal vein and hepatic artery, we recommend Doppler ultrasound
      and abdominal aortography, a less invasive angiographic procedure.

PMID- 8875871
TI  - Venous return by the paraumbilical and hepatic veins in case of superior vena
      cava obstruction.
AB  - Pseudolesion in segment IV of the liver is a well-known diagnostic pitfall during
      arterial portography or even spiral computed tomography (CT) of the liver. It has
      suggested that this pseudolesion is the result of an abnormality in subsegmental
      perfusion. We report a case of an early dense contrast enhancement of segment IV
      of the liver by epigastric and paraumbilical veins in a patient with a superior
      vena cava obstruction. A pseudolesion in segment IV was observed in this patient
      on a spiral CT of the liver obtained during the portal phase.

PMID- 8875872
TI  - Gallbladder opacification 12-24 h after angiography by CT examination: a
      multivariate analysis.
AB  - BACKGROUND: To examine the incidence and predisposing factors of gallbladder
      opacification in delayed computed tomography (CT) after angiography. METHODS: CT
      examination 12-24 h after angiography was performed in 389 patients. Univariate
      and multivariate analyses were made. RESULTS: Two hundred thirty-three of 389
      patients (60%) revealed gallbladder opacification. Type of contrast medium (P <
      0. 01), total bilirubin (P < 0.01), and serum creatinine (P < 0.01) were
      significant and independent factors relating to gallbladder opacification.
      Ioxaglate (70%, relative odds = 2.86) and iohexol (63%, relative odds = 2.03)
      showed higher gallbladder opacification rates than that of iopamidol (45%,
      relative odds = 1.43) and diatrizoate (30%). Patients with a lower serum
      bilirubin level (relative odds = 1.67) and a raised serum creatinine level
      (relative odds = 2.01) showed higher incidence of gallbladder opacification.
      CONCLUSION: Gallbladder opacification after angiography is not an abnormal
      finding on delayed CT in patients with not only abnormal renal function but also
      normal hepatobiliary and normal renal function, especially for modern contrast
      media.

PMID- 8875873
TI  - Evolution of the infected abdominal aortic aneurysm: CT observation of early
      aortitis.
AB  - Infected aortic aneurysm is an uncommon, life-threatening disease. Early surgical
      treatment is crucial to survival. An early diagnosis could be made on CT in
      suspected cases, although CT features of infectious aortitis overlap with
      retroperitoneal fibrosis, hemorrhage, and lymphadenopathy. We report the case of
      an infected abdominal aortic aneurysm and describe the additional potentially
      useful CT finding of early infectious aortitis, which helps localize the
      abnormality to the aortic wall.

PMID- 8875874
TI  - Three-dimensional CT imaging of an isolated dissecting aneurysm of the superior
      mesenteric artery.
AB  - A case of an isolated dissecting aneurysm of the superior mesenteric artery is
      presented with findings of three-dimensional CT imaging. False lumen, intimal
      flap, entry, and re-entry are clearly identified on three-dimensional CT imaging.

PMID- 8875875
TI  - Helical CT anatomy of pancreatic arteries.
AB  - BACKGROUND: To assess the frequency of visualization of pancreatic arteries in
      the arterial phase of helical computed tomography (CT). METHODS: The visibility
      of pancreatic and peripancreatic arteries in helical CT images was evaluated in
      20 consecutive patients who had no evidence of pancreatic disease. CT
      examinations were performed by using a continuously rotating CT scanner and
      intravenous injection of contrast media. The scans were taken 35 s after the
      start of injection and with a table speed of 3 mm/s. Images were reconstructed in
      3-mm section increments. RESULTS: Frequently visualized arteries were the
      gastroduodenal, anterior and posterior superior pancreaticoduodenal, and right
      gastroepiploic arteries. Infrequently visualized arteries were the dorsal
      pancreatic, pancreatica magna, caudal pancreatic, transverse pancreatic, and
      common, anterior, and posterior inferior pancreaticoduodenal arteries.
      CONCLUSION: Helical CT enabled us to recognize small pancreatic arteries, and the
      evaluation of these arteries should be considered in the staging of pancreatic
      carcinoma.

PMID- 8875876
TI  - Lipoma-induced jejunojejunal intussusception: US and CT diagnosis.
AB  - A case study of a patient who presented with abdominal pain and a palpable
      mesogastric mass is discussed. Ultrasound and computed tomography (CT)
      demonstrated that the palpable mass was jejunojejunal intussusception of the
      small intestine. The lead point of the intussusception was a lipoma that appeared
      in the CT scan as a small intramural mass with an attenuation coefficient of fat.

PMID- 8875877
TI  - Saline-filled appendiceal ultrasonography in clinically equivocal acute
      appendicitis.
AB  - BACKGROUND: To establish the value of saline-filled appendiceal ultrasonography
      in the the diagnosis of clinically equivocal acute appendicitis. METHODS: Saline
      filled ultrasonography was performed in 43 patients with an equivocal clinical
      diagnosis of acute appendicitis. RESULTS: Sonography diagnosed 31 of 32 patients
      without acute appendicitis (97%). A normal appendix was visualized in 15 patients
      (47%), and we identified a normal appendix in 15 of 22 patients (68%) in whom the
      colon was cleansed with Golytely(R). Sonography diagnosed 10 of 11 patients with
      acute appendicitis (91%). In three of 10 patients, the findings corresponded to
      sonographic pitfalls. CONCLUSION: Saline-filled appendiceal ultrasonography
      enables the detection of a normal appendix and may overcome sonographic pitfalls
      in acute appendicitis.

PMID- 8875878
TI  - Giant colonic diverticulum: presentation of one case and review of the
      literature.
AB  - Since the first case described in 1946, fewer than 100 cases of giant colonic
      diverticula have been reported in the literature. We discuss the clinical,
      radiologic, and pathologic findings in a case of giant colonic diverticulum and
      review the etiology and differential diagnosis.

PMID- 8875879
TI  - Neurogenic bladder in infants and children--a new challenge for the radiologist.

PMID- 8875880
TI  - The renal axes in spina bifida: issues of confusion and fusion.
AB  - The occurrence of horseshoe kidneys in myelodysplasia has been suggested to be
      overestimated because of the concurrent prevalence of kyphotic spine in the spina
      bifida population. Pseudohorseshoe kidneys result from the actual medial
      migration and apposition of the lower renal poles in the deep fossa created by
      the gibbus deformity. The presence of a lumbosacral kyphosis, however, does not
      imply there is not a true horseshoe kidney. In our myelodysplasia population of
      189 patients, occurrence of true horseshoe kidneys (13 patients) and
      pseudohorseshoe kidneys (14 patients) was increased. The finding of lumbosacral
      kyphosis was twice as common in the pseudohorseshoe population as in the true
      horseshoe population. True horseshoe kidneys were three times more commonly seen
      in association with congenital vertebral anomalies cephalad to the dysraphic
      spine. Diagnosis in this study was predominantly based on renal cortical
      scintigraphy with the posterior pin-hole magnification technique.

PMID- 8875881
TI  - Perirenal fat necrosis secondary to hemorrhagic pancreatitis, mimicking
      retroperitoneal liposarcoma: CT manifestation.
AB  - A case of resolving hemorrhagic pancreatitis resulting in massive left perirenal
      fat necrosis is reported. CT revealed a huge fat-containing mass that was thought
      to be retroperitoneal liposarcoma before operation. Pancreatitis with perirenal
      involvement is rarely encountered as a retroperitoneal mass.

PMID- 8875882
TI  - Intrarenal varices in portal hypertension: demonstration by color Doppler
      imaging.
AB  - The gray-scale ultrasonographic appearances of dilated intrarenal vascular
      structures may mimic peripelvic cysts or hydronephrosis. We report a patient with
      portal hypertension in whom color Doppler ultrasound was found to be a very
      practical imaging technique in demonstrating varices of the renal segmental
      veins.

PMID- 8875883
TI  - Transrectal color Doppler ultrasonography for postejaculation hematuria.
AB  - A case involving an adult man with postejaculation hematuria (PEH) is described.
      We used transrectal color Doppler ultrasonography to evaluate periprostatic or
      intraprostatic vascular anomalies. We confirmed a vascular anomaly by angiography
      and embolized it. Periprostatic vascular anomaly may be a cause of PEH, and color
      Doppler ultrasonography is helpful for the initial studies of this entity.

PMID- 8875884
TI  - Vaginal arteriovenous malformation: MR imaging.
AB  - Vaginal arteriovenous malformations (AVMs), although rare, can lead to life
      threatening complications. We report the first case of a vaginal AVM whose
      diagnosis and follow-up were performed by magnetic resonance imaging (MRI). MRI
      findings of the AVM are the blood flow-related features within the tumor, such as
      the phase-shift artifact, paradoxical enhancement, and flow voids.

PMID- 8875885
TI  - A new mouse mutation causing male sterility and histoincompatibility.
AB  - Male sterility and histoincompatibility, mshi, is an autosomal recessive mutation
      in BALB/cBy mice that causes reduced testis size and sterility in homozygous
      males. The testes of homozygous mutants are highly disorganized and appear to
      have a block in the regulation of male germ cell proliferation. No heterozygous
      effect is detectable. Reproduction is unaffected in females carrying the
      mutation. The mutation also affects histocompatibility; most homozygous males and
      females reject sex-matched skin grafts from BALB/cBy mice. We used an intercross
      between BALB/cBy and CAST/Ei to map the mshi mutation to the proximal end of
      Chromosome (Chr) 10. The most likely gene order places the mutation between
      D10Mit80 and D10Mit16, near the interferon gamma receptor locus, Ifgr, which may
      be a candidate gene for this mutation.

PMID- 8875886
TI  - Scrambler, a new neurological mutation of the mouse with abnormalities of
      neuronal migration.
AB  - A novel spontaneous neurological mutation, scrambler (scm), appeared in the
      inbred mouse strain DC/Le (dancer) in 1991. Mice homozygous for this recessive
      mutation are recognized by an unstable gait and whole-body tremor. The cerebella
      of 30-day-old scrambler homozygotes are hypoplastic and devoid of folia; however,
      neither seizures nor abnormal brain wave patterns have been observed. Homozygous
      scrambler mutants have an ataxic gait which in the male may be a contributory
      factor in the failure to mate. Female homozygotes mate and breed. Life span is
      not reduced in either sex. Scrambler is similar to the reeler mutation in
      phenotype and pathology and, like reeler, probably results from defective
      neuronal migration. We mapped the scrambler mutation to Chromosome (Chr) 4,
      proving that it is distinct from the recently cloned reeler gene on Chr 5. We
      also determined the map position of the agrin gene, Agrn, on Chr 4, and on this
      basis eliminated it as a candidate for scm. Currently there is no known homology
      of scrambler with human lissencephalies or other human disorders caused by
      abnormal neuronal migration.

PMID- 8875887
TI  - Mouse USF1 gene cloning: comparative organization within the c-myc gene family.
AB  - Upstream stimulatory factors (USF/MLTF) belong to the c-myc family of
      transcription factors. Through binding to target DNA as dimers, the ubiquitous
      USF proteins regulate a variety of genes. USF proteins are encoded by two genes,
      USF1 and USF2. Protein sequences of USF1 and 2 are highly homologous across
      species, suggesting functional conservation. To determine whether the genomic
      organization was conserved between USF1 and USF2, we isolated the murine USF1
      gene and characterized its genomic structure. Both genes are similarly organized
      in 10 exons spanning over 10 kbp. By the 5'-rapid amplification of cDNA ends and
      S1 nuclease mapping methods, exon 1 was defined and the transcription initiation
      sites were mapped. The sequence of 8 kb of the gene, including 1.75 kb of 5'
      flanking DNA, was determined. The promoter region is GC rich and lacks a typical
      TATA or CCAAT element. Strikingly, a comparison of the murine and human
      untranslated sequences reveals regions that exhibit greater than 73% sequence
      identity. A genomic alignment of the dimerization and DNA binding domains is
      presented for five genes of the c-myc family, suggesting a hypothetical common
      ancestor gene.

PMID- 8875888
TI  - Isolation of a cDNA encoding the rat MAP-kinase homolog of human p63mapk.
AB  - Using a combination of screening, RACE, and RT-PCR, we have isolated a new rat
      brain cDNA, we refer to as rMNK2, that showed strong homology to known MAP
      kinases. The deduced amino acid sequence of rMNK2 indicated that it is the rat
      homolog of human p63(mapk), showing 94.5% identity. rMNK2 showed 77% homology
      with rat ERK3 and its human homolog p97(mapk), and 43% homology with both rat
      genes rMNK1(ERK1) and ERK2, within the kinase domain. This suggest that rMNK2 and
      ERK3 belong to a separate subfamily within the rat MAP-kinase multigene family.
      The most interesting difference lies in subdomain VIII, where this new subfamily
      contain a SEG/SPR motif instead of the TEY/APE found in the ERK subfamily, the
      TPY/APE found in the JNK/SAPK subfamily or the TGY/APE found in the p38/RK
      subfamily. The human homologs of ERK3 and rMNK2 (p97(mapk) and p63(mapk)) also
      show this significant change. Expression of rMNK2 has been detected in brain and
      to a lesser extent in lung by reverse transcription/PCR (RT-PCR). In situ
      hybridization of rat brain slices demonstrated a restricted expression of rMNK2
      in the choroid plexus and hippocampus. This is interesting because the human
      homolog p63(mapk) maps to 18q12-21, a region that might be implicated in manic
      depressive illness.

PMID- 8875889
TI  - Swine cytosolic malic enzyme: cDNA cloning, sequencing, and localization.
AB  - A highly significant genetic association has been found between some alleles of
      the swine Major Histocompatibility Complex SLA (Swine Leukocyte Antigen genetic
      complex) and the cytosolic malic enzymatic activity level in muscles. The aim of
      this study was to find out whether this genetic association was due to a close
      linkage of the SLA region and the gene coding for the enzyme. Since no swine
      cytosolic malic enzyme sequence (ME1) was available, we isolated several
      overlapping fragments that spanned the almost entire malic enzyme transcript both
      by screening of a swine cDNA library and by RT-PCR. The results indicated the
      existence of two transcripts of 2. 0 and 3.1 kb, which probably correspond to two
      alternative forms of one gene. The sequence of the transcript was highly similar
      to the other published mammalian cytosolic NADP+-dependent malic enzyme cDNA,
      especially within the four functional domains. Two major bands at 3.7 and 2.4 kb
      were detected on Northern blots containing the RNA from 25 tissues from fetuses
      and adult pigs. A high expression level was found in the adrenal gland, muscle,
      liver, and peripheral nerves. The analysis of malic enzyme RFLPs in five SLA
      informative families revealed an independent segregation of the ME1 gene from the
      SLA region. In situ hybridization results localized the cytosolic malic enzyme on
      the swine Chromosome (Chr) 1p1.2, except that the association between SLA and the
      malic enzyme activity level was due to a physical genetic linkage. Thus, the
      mechanisms underlying this association remain to be elucidated.

PMID- 8875891
TI  - Synteny mapping in river buffalo.
AB  - The cosegregation of ten coding loci has been investigated, in a panel of 37
      somatic cell hybrids resulting from the fusion of a hamster cell line and river
      buffalo lymphocytes, by use of Southern hybridization technique. Five syntenic
      groups, TCRB-PGY3, ASS-ABL, FUCA1P-CRYG, MBP-YES1, and CGN1-ACTA1, previously
      assigned to cattle as U13, U16, U17, U28, and U29 respectively, were also found
      to be syntenic in buffalo. Based on the extensive syntenic conservation and
      banding homology between cattle and river buffalo, comparative mapping predicts
      the localization of these syntenic groups on river buffalo Chromosomes (Chrs)
      :BBU7, BBU12, BBU2q, BBU22, and BBU4q respectively as they have been previously
      localized on cattle Chrs BTA4, BTA11, BTA2, BTA24 & BTA28.

PMID- 8875890
TI  - Pigs with the dominant white coat color phenotype carry a duplication of the KIT
      gene encoding the mast/stem cell growth factor receptor.
AB  - Comparative mapping data suggested that the dominant white coat color in pigs may
      be due to a mutation in KIT which encodes the mast/stem cell growth factor
      receptor. We report here that dominant white pigs lack melanocytes in the skin,
      as would be anticipated for a KIT mutation. We found a complete association
      between the dominant white mutation and a duplication of the KIT gene, or part of
      it, in samples of unrelated pigs representing six different breeds. The
      duplication was revealed by single strand conformation polymorphism (SSCP)
      analysis and subsequent sequence analysis showing that white pigs transmitted two
      nonallelic KIT sequences. Quantitative Southern blot and quantitative PCR
      analysis, as well as fluorescence in situ hybridization (FISH) analysis,
      confirmed the presence of a gene duplication in white pigs. FISH analyses showed
      that KIT and the very closely linked gene encoding the platelet-derived growth
      factor receptor (PDGFRA) are both located on the short arm of Chromosome (Chr) 8
      at band 8p12. The result revealed an extremely low rate of recombination in the
      centromeric region of this chromosome, since the closely linked (0.5 cM) serum
      albumin (ALB) locus has previously been in situ mapped to the long arm (8q12).
      Pig Chr 8 shares extensive conserved synteny with human Chr 4, but the gene order
      is rearranged.

PMID- 8875892
TI  - Degeneracy in human multicopy RBM (YRRM), a candidate spermatogenesis gene.
AB  - In order to search for mutations in the multicopy RBM genes that might be
      associated with male infertility, we have used sequence data from the reported
      cDNA clone to determine the intron exon boundaries of the YRRM 1 gene. This gene
      has 12 exons, three of which encode the putative RNA binding domain of the
      protein. Different copies of the gene contain sequence variations and,
      additionally, give rise to transcripts with different numbers of copies of the
      repeated SRGY motif. Since mutations in the RNA binding domain would seem likely
      to have an effect on the activity of the protein, we have scanned these exons for
      mutations by SSCP on DNA from normal and infertile men. Sequence differences in
      the exon encoding the N-terminal part of the RNA binding domain account for at
      least four different classes of the gene and give rise to different SSCP
      conformers. Sequence analysis shows that one of these classes is a pseudogene and
      that the members of another class are nonfunctional. RT-PCR shows that all
      classes are transcribed and that the A class is most abundant. We have found a
      point mutation that alters the highly conserved RNP2 motif in one infertile
      patient. This mutation is also found in his father. We have used PCR followed by
      SSCP analysis to map RBM on a Y Chromosome (Chr) YAC contig and have demonstrated
      a distribution that spans a major part of this chromosome's euchromatin.

PMID- 8875893
TI  - Molecular analysis of two new Steel mutations in mice shows a transversion or an
      insertion.

PMID- 8875894
TI  - The mouse gene (Mobp) encoding myelin-associated oligodendrocytic basic protein
      maps to distal chromosome 9.

PMID- 8875895
TI  - Localization of human and mouse N-ethylmaleimide-sensitive factor (NSF) gene: a
      two-domain member of the AAA family that is involved in membrane fusion.

PMID- 8875896
TI  - Intrachromosomal telomere-like DNA sequences in Chinese hamster.

PMID- 8875897
TI  - Genomic cloning and genetic mapping of the rat Nramp1 (Bcg) gene on chromosome 9.

PMID- 8875898
TI  - Mapping the ovine genes encoding IL3, IL4, IL5, and CSF2 to sheep chromosome 5q13
      q15 by FISH.

PMID- 8875899
TI  - Chromosome localization of the genes for growth hormone, somatostatin peptide,
      ornithine transcarbamylase, and prion protein in silver fox (Vulpes fulvus).

PMID- 8875900
TI  - Sequence of a fourth human CALM II-related pseudogene (CALM II psi4).

PMID- 8875901
TI  - The methylenetetrahydrofolate reductase (Mthfr) gene maps to distal mouse
      chromosome 4.

PMID- 8875902
TI  - A major polymorphism in the rat SA gene caused by the insertion of a LINE
      element.

PMID- 8875903
TI  - Localization of the vasopressin gene to rat chromosome 3.

PMID- 8875904
TI  - Genetic mapping of the laminin gamma 2 gene on sheep chromosome 12.

PMID- 8875905
TI  - Fluorescent in situ localization of the bovine activin receptor type IIA locus on
      chromosome 2 (2q2.3-2.4).

PMID- 8875906
TI  - Clostripain linker deletion variants yield active enzyme in Escherichia coli: a
      possible function of the linker peptide as intramolecular inhibitor of
      clostripain automaturation.
AB  - The clostripain core protein is composed of the light and heavy chain subunits
      linked by a nonapeptide into a single polypeptide chain [Mol. Gen. Genet. 240:
      140, 1993]. Linker removal is due to autocatalytic processing yielding active
      heterodimeric enzyme. We have expressed mutationally altered core protein
      variants in the heterologous host Escherichia coli to gain further insight into
      the process of clostripain automaturation. In a mutationally created Cys231 -->
      Ser variant, heterodimer formation was largely impaired, providing molecular
      evidence that the capacity for automaturation is attributed to the active site
      cysteine, Cys231, of the native enzyme. Artificially generated deletions of the
      linker peptide did not prevent the formation of active enzyme. One variant gave
      rise to a single-chain molecule devoid of the authentic processing sites while
      retaining enzymatic activity. Experiments performed with linker substitution
      variants suggested that the efficacy of automaturation depends on a proper
      configuration of the linker region. According to computerized predictions, the
      formation of a turn-structured protein loop or hinge with hydrophilic
      characteristics in the linker region is probably a prerequisite for the
      interaction of the active site cysteine with the processing sites, Arg181 and
      Arg190. We propose that the clostripain linker nonapeptide serves as an important
      transient intramolecular inhibitor in the cellular self-defense program evolved
      by the natural host Clostridium histolyticum.

PMID- 8875907
TI  - The naturally transformable marine bacterium WJT-1C formally identified as
      "Vibrio" is a pseudomonad.
AB  - A marine bacterial isolate, previously identified as Vibrio WJT-1C (ATCC 55351)
      and used as a model for investigating the process of natural transformation in
      the marine environment, has been further examined to determine its taxonomic
      identity. API 20E test strips, phenotypic testing, and flagellar staining had
      previously assigned the strain to the genus Vibrio, most closely related to V.
      campbelli. 16S rRNA analysis indicated that WJT-1C was in the Pseudomonas
      subgroup of the gamma proteobacteria. Bacteriophage typing and natural
      transformation with chromosomal DNA indicated that it was distinct from
      previously described marine transforming pseudomonads including Pseudomonas
      stutzeri strain JM300. The importance and abundance of the Pseudomonas subgroup
      of the gamma proteobacteria in the environment suggest that these marine strains
      are well suited as model organisms for describing the process and importance of
      natural transformation in nature.

PMID- 8875908
TI  - Accelerated Biodegradation of High and Low Concentrations of p-Nitrophenol (PNP)
      by Bacterial Inoculation in Industrial Wastewater: The Role of Inoculum Size on
      Acclimation Period
AB  - The effect of inoculum size on the acclimation period and rate and extent of p
      nitrophenol (PNP) degradation at high (1-10 mg/L) and low (26 &mgr;g/L)
      concentrations for two bacteria was determined in defined media as well as
      industrial wastewater. Increased inoculum size did not affect the acclimation
      period of either bacterium at high (1-10 mg/L) PNP concentrations. At low PNP
      concentrations (26 &mgr;g/L), the two bacteria behaved differently. The
      acclimation period was shortened and both the rate and extent of mineralization
      of PNP were enhanced by increasing the Corynebacterium sp. inoculum size from 3 x
      10(5) to 3 x 10(6) cells/ml. Addition of phosphate or elimination of predators
      also reduced the acclimation period. Conversely, increasing the inoculum size
      from 3 x 10(5) to 5 x 10(6) cells/ml of Pseudomonas putida lengthened the
      acclimation period and reduced both the rate and extent of mineralization. It is
      suggested that, in a given environment, the success of an introduced species to
      enhance the degradation of a chemical depends upon (i) concentration of the
      chemical, (ii) selection of an appropriate microorganism, and (iii) utilization
      of a suitable inoculum size.

PMID- 8875909
TI  - Purification and Characterization of an Extracellular beta-Glucosidase from the
      Wood-Grown Fungus Xylaria regalis
AB  - Xylaria regalis, a wood-grown ascomycete isolated in Taiwan, produces beta
      glucosidase (EC 3.2.1.21) extracellularly. The beta-glucosidase was purified to
      homogeneity by ammonium sulfate precipitation, ion-exchange, and gel filtration
      chromatography. The molecular mass of the purified enzyme was estimated to be 85
      kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With p
      nitrophenyl beta-D-glucopyranoside (PNPG) as the substrate at pH 5.0 and
      50&deg;C, the Km was 1.72 mM and Vmax was 326 &mgr;mol/min/mg. Optimal activity
      with PNPG as the substrate was at pH 5.0 and 50&deg;C. The enzyme was stable at
      pH 5.0 at temperatures up to 50&deg;C. The purified beta-glucosidase was active
      against PNPG, cellobiose, sophorose, and gentiobiose, but did not hydrolyze
      lactose, sucrose, Avicel, and o-nitrophenyl beta-D-galactopyranoside. The
      activity of beta-glucosidase was stimulated by Ca2+, Mg2+, Mn2+, Cd2+ and beta
      mercaptoethanol, and inhibited by Ag+, Hg2+, SDS, and p-chloromercuribenzoate
      (PCMB).

PMID- 8875910
TI  - Influence of Carbohydrates on the alpha-Galactosidase Activity of Lactobacillus
      fermentum
AB  - The influence of soybean galactosaccharides (stachyose, raffinose, melibiose) as
      well as galactose and glucose on the synthesis and activity of alpha
      galactosidase (alpha-gal) from Lactobacillus fermentum CRL 251 was studied.
      Stachyose was the most effective inducer, followed by melibiose, raffinose, and
      galactose; scarce activity was detected with glucose. Exogenously supplied
      glucose inhibited the synthesis of the enzyme in cultures of L. fermentum growing
      on galactose. This effect was reversed by the addition of cyclic adenosine-3',5'
      monophosphate (cAMP), which suggests that this compound could be involved in the
      regulation of alpha-gal synthesis.

PMID- 8875911
TI  - In vitro metabolism of the stereoisomers of 2,6-diaminopimelic acid by mixed
      rumen protozoa and bacteria.
AB  - Formation of lysine from stereoisomers (SI) of 2,6-diaminopimelic acid (DAP) and
      the epimerization between the three SI of DAP (DAP-SI) by rumen protozoa and
      bacteria were examined. Mixed rumen protozoa (P) and bacteria (B) were isolated
      from the rumen of goats given a concentrate and hay cubes and incubated
      separately with and without a mixture and a single one of the three DAP-SI. In P
      suspensions, mixed DAP-SI decreased by 10.59% as a whole and converted mainly to
      lysine by 8.41% during 12 h incubation. When meso-, L- and D-DAP were added
      singly to the media, the results showed that each DAP-SI interconverted and
      produced lysine. This means that mixed rumen protozoa have an ability to
      synthesize lysine from not only meso-DAP but also from D- and L-DAP, though
      probably via meso-DAP, and hence have DAP epimerase activities for the reversal
      conversion of each DAP-SI. This is the first discovery to show the
      interconversion of DAP-SI and synthesis of lysine from them by protozoa. In B
      suspensions, mixed DAP-SI decreased by 10.92% as a whole and converted to lysine
      by 4.20% during 12 h incubation. When a single DAP-SI was added to the media,
      meso-, L- and D-DAP were interconverted and then converted to lysine by the rumen
      bacteria as well as the protozoa. This also means that mixed rumen bacteria have
      DAP epimerase activities to interconvert DAP-SI and have an ability to synthesize
      lysine from not only meso-DAP but also from L- and D-DAP, and this is also the
      first finding in rumen bacteria.

PMID- 8875912
TI  - Methods for increasing survivability during storage of exponentially growing
      bacteria.
AB  - A protocol has been developed for storing Gram (-) bacterial cells at 0 degrees
      C, which allows greater than 90% of stored cells to retain colony-forming ability
      for up to 60 days. The protocol, which yields essentially identical results when
      used with Escherichia coli or Pseudomonas aeruginosa, does not enhance
      survivability of Bacillus cereus. The greatest and longest survival is enjoyed
      when exponentially growing cells in minimal-glucose medium are deprived of carbon
      for about 9 h, supplemented with 750 microg/ml chloramphenicol, and immediately
      placed at 0 degrees C. By decreasing the period of carbon starvation from 9 to 5
      h, or increasing the period of carbon starvation from 9 to 12 h, both the
      ultimate survival rate and kinetics of loss of culturability are affected.
      Survival enhancement induced by chloramphenicol is not similarly induced by
      kanamycin.

PMID- 8875913
TI  - Inhibition of spiralin processing by the lipopeptide antibiotic globomycin.
AB  - The cyclic lipopeptide globomycin, a specific inhibitor of signal-peptidase II
      (Lsp A), proved toxic for the mollicute Spiroplasma melliferum with a minimal
      inhibitory concentration (MIC) in the range 6.25-12.5 microM, about one order of
      magnitude higher (that is, less efficient) than bee-venom mellitin. SDS-PAGE
      analysis of cell proteins followed by immunolabeling ("Western blotting") and by
      crossed immunoelectrophoresis demonstrated that the cleavage of the prespiralin
      leader peptide was prevented by globomycin. Cell fractionation experiments showed
      that prespiralin was membrane bound and did not accumulate in the cytoplasm or in
      the culture medium. Furthermore, the use of the potential-sensitive fluorescent
      dye 3,3'-dipropyl-2,2'-thiadicarbocyanine iodide (diS-C3-[5]) revealed that, in
      contrast to valinomycin and mellitin, globomycin up to 30 microM has no effect on
      the electrical transmembrane potential of S. melliferum. This indicates that the
      toxicity of globomycin for spiroplasma cells is mainly if not exclusively owing
      to the inhibition of spiralin processing. Added to previously published data,
      these results suggest that spiralin and probably other lipoproteins of mollicutes
      are acylated and membrane targeted by a mechanism involving notably the
      processing of the prelipoprotein precursor by a type II, globomycin-sensitive
      signal peptidase.

PMID- 8875914
TI  - Extranuclear expression of the bacterial xylose isomerase (xylA) and the UDP
      glucose dehydrogenase (hasB) genes in yeast with Kluyveromyces lactis linear
      killer plasmids as vectors.
AB  - On the basis of the linear killer plasmid pGKL1 from Kluyveromyces lactis, two
      new linear hybrid plasmids were constructed. One of these, pRSC126, carried the
      xylA gene from Streptomyces rubiginosus encoding the xylose isomerase. The other
      linear hybrid molecule, pRSC128, carried the hasB gene of Streptococcus pyogenes
      encoding the UDP glucose dehydrogenase. Construction was performed in a way that
      the putative cytoplasmic promoter element of ORF5 of pGKL2 was fused to the
      coding region of the heterologous genes. After transformation, in vivo
      recombination led to the establishment of linear hybrid vectors. Though
      efficiency of expression was low when compared with bacterial systems,
      cytoplasmic expression of both genes was clearly demonstrated.

PMID- 8875915
TI  - Proposed topology of the glucitol permeases of Escherichia coli and Clostridium
      acetobutylicum.

PMID- 8875916
TI  - Isolation of Ewingella americana from the cultivated mushroom, Agaricus bisporus.
AB  - The isolation of Ewingella americana, an unusual Enterobacteriaceae, is reported
      here for the first time in a non-animal reservoir. Thirty-five strains of E.
      americana have been recovered from the cultivated mushroom, Agaricus bisporus.
      The biochemical characteristics of these strains are consistent with previously
      published descriptions of this species recovered from clinical specimens and from
      molluscs. DNA reassociation analysis was used to confirm the identity of mushroom
      derived E. americana, and restriction fragment length polymorphism was used to
      reliably differentiate strains that otherwise demonstrated little phenotypic
      variation.

PMID- 8875917
TI  - Clinical and pathological features of ovarian cancer in women with germ-line
      mutations of BRCA1.
AB  - BACKGROUND: We tested the hypothesis that ovarian cancers associated with germ
      line mutations of BRCA1 have distinct clinical and pathological features as
      compared with sporadic ovarian cancers. METHODS: We reviewed clinical and
      pathological data on patients with primary epithelial ovarian cancer found to
      have germ-line mutations of BRCA1. Survival among patients with advanced-stage
      cancer and such mutations was compared with that in control patients matched
      stage, grade, and histologic subtype of the tumors. A combination of single
      strand conformation and sequencing analyses was used to examine the 22 coding
      exons and intronic splice-donor and splice-acceptor regions of BRCA1 for
      mutations in pathological specimens. Alternatively, some patients were known to
      be obligate carriers of the mutant BRCA1 gene because of their parental
      relationships with documented mutant-gene carriers. RESULTS: We identified 53
      patients with germ-line mutations of BRCA1. The average age at diagnosis was 48
      years (range, 28 to 78). Histologic examination in 43 of the 53 patients showed
      serous adenocarcinoma. Thirty-seven tumors were of grade 3, 11 were of grade 2, 2
      were of grade 1, and 3 were of low malignant potential. In 38 patients, the
      tumors were of stage III; 9 patients (including those with tumors of low
      malignant potential) had stage I disease, 5 had stage IV, and 1 had stage II. As
      of June 1996, with a median follow-up among survivors of 71 months from
      diagnosis, 20 patients had died of ovarian cancer, 27 had no evidence of the
      disease, 4 were alive with the disease, and 2 had died of other diseases.
      Actuarial median survival for the 43 patients with and advanced-stage disease was
      77 months, as compared with 29 months for the matched controls (P<0.001).
      CONCLUSIONS: As compared with sporadic ovarian cancers, cancers associated with
      BRCA1 mutation appear to have a significantly more favorable clinical course.

PMID- 8875918
TI  - Clinical outcome of mitral regurgitation due to flail leaflet.
AB  - BACKGROUND: Mitral regurgitation due to flail leaflet is difficult to manage,
      because it is frequently asymptomatic yet carries a high risk of left ventricular
      dysfunction and because the natural history of the condition is poorly defined.
      METHODS: We obtained clinical follow-up data through 1994-1995 in 229 patients
      with isolated mitral regurgitation due to flail leaflet; this condition was first
      diagnosed by echocardiography between 1980 and 1989. RESULTS: The 86 patients who
      were treated medically had a mortality rate significantly higher than expected
      (6.3 percent yearly, P=0.016 for the comparison with the expected rate in the
      U.S. population according to the 1990 census). Independent determinants of
      mortality were an older age, the presence of symptoms, and a lower ejection
      fraction. Patients who were even transiently in New York Heart Association
      functional class III or IV had a high mortality rate (34 percent yearly), but the
      rate was also notable (4.1 percent yearly) among those in class I or II. At 10
      years, the mean (+/- SE) rates of heart failure, atrial fibrillation, and death
      or surgery were 63 +/- 8, 30 +/- 12, and 90 +/- 3 percent, respectively. In a
      multivariate analysis, surgical correction of mitral regurgitation (performed in
      143 patients) was associated with a reduced mortality rate (hazard ratio, 0.29;
      95 percent confidence interval, 0.15 to 0.56; P<0.001). CONCLUSIONS: When treated
      medically, mitral regurgitation due to flail leaflet is associated with excess
      mortality and high morbidity. Surgery is almost unavoidable within 10 years after
      the diagnosis and appears to be associated with an improved prognosis; this
      finding suggests that surgery should be considered early in the course of the
      disease.

PMID- 8875919
TI  - An echocardiographic study of valvular heart disease associated with systemic
      lupus erythematosus.
AB  - BACKGROUND: Valvular heart disease is the most important cardiac manifestation of
      systemic lupus erythematosus. We performed a study to determine the relation of
      valvular disease to other clinical features of lupus, whether or not the valve
      disease progresses, and the associated morbidity and mortality. METHODS: We
      performed transesophageal echocardiography and rheumatologic evaluations in 69
      patients with systemic lupus erythematosus. The echocardiographic findings were
      compared with those in 56 healthy volunteers. Fifty-eight patients (84 percent)
      had second evaluations a mean (+/-SD) period of 29 +/- 13 months later. The
      patients and controls were followed for 57 months. RESULTS: Valvular
      abnormalities were common on the initial and the follow-up echocardiograms (in 61
      and 53 percent of the patients, respectively). Valvular thickening was the
      predominant finding initially and on follow-up (in 51 and 52 percent of the
      patients, respectively), followed by vegetations (in 43 and 34 percent), valvular
      regurgitation (in 25 and 28 percent), and stenosis (in 4 and 3 percent). Valvular
      abnormalities frequently resolved, appeared for the first time, or persisted but
      changed in appearance or size between the two studies. Mild or moderate valvular
      regurgitation did not progress to become severe, and new stenoses did not
      develop. Neither the presence of valvular disease nor changes in the
      echocardiographic findings were temporally related to the duration, activity, or
      severity of lupus or to its treatment. The combined incidence of stroke,
      peripheral embolism, heart failure, infective endocarditis, and the need for
      valve replacement was 22 percent in the patients with valvular disease, but only
      8 percent in those without it. A total of seven patients died during follow-up,
      in most cases as a result of valvular disease. Valvular abnormalities and
      complications were uncommon in the controls (occurring in 9 and 2 percent,
      respectively). CONCLUSIONS: Valvular heart disease is common in patients with
      systemic lupus erythematosus, frequently changes over time, appears to be
      temporally unrelated to other clinical features of lupus, and is associated with
      substantial morbidity and mortality.

PMID- 8875920
TI  - Early progression of disease in HIV-infected infants with thymus dysfunction.
AB  - BACKGROUND: Infants with congenital thymic deficiency (the DiGeorge syndrome)
      have immunodeficiency and a characteristic pattern of low CD4+ and CD8+ T
      lymphocyte counts and low CD5+ B-lymphocyte counts. Because the thymus is
      essential for the generation of CD4+ cells, we sought evidence of thymus
      dysfunction in infants infected perinatally with the human immunodeficiency virus
      (HIV). METHODS: We studied the immunophenotypes of 59 infants with maternally
      transmitted HIV, 5 infants with the DiGeorge syndrome, and 168 infants exposed to
      HIV but not infected. The criteria for a presumed thymic defect were reductions
      in both the CD4+ and CD8+ T-cell subgroups during the first six months of life
      that were confirmed in a subgroup of infants by low counts of CD4+CD45RA+ and
      CD4+CD45RO+ T cells and CD5+ B cells. RESULTS: Of the 59 HIV-infected infants, 17
      had immunophenotypes similar to those of infants with the DiGeorge syndrome. The
      risks of the acquired immunodeficiency syndrome (AIDS) by the ages of 12 and 24
      months were 75 percent and 92 percent in these 17 infants, as compared with 14
      and 34 percent in the other 42 infants (P<0.001). Nine of the HIV-infected
      infants with the DiGeorge-like immunophenotype (53 percent) died within six
      months of the progression to AIDS, as compared with only three of the other
      infants (7 percent, P=0.006). CONCLUSIONS: In some infants infected perinatally
      with HIV, a pattern of lymphocyte depletion develops that resembles the pattern
      in congenital thymic deficiency. Since HIV disease progresses rapidly in such
      infants, they may be candidates for early antiviral therapy and attempts at
      immune reconstitution.

PMID- 8875921
TI  - Images in clinical medicine. Klebsiella pneumoniae.

PMID- 8875922
TI  - Injuries due to firearms in three cities.
AB  - BACKGROUND: To describe the incidence and outcome of injuries due to firearms, we
      conducted a population-based study of fatal and nonfatal gunshot wounds in three
      cities: Memphis, Tennessee; Seattle; and Galveston, Texas. METHODS: Records of
      the police, medical examiners, ambulance crews, and hospital emergency
      departments and hospital admissions were monitored to identify all injuries
      caused by firearms that were severe enough to prompt emergency medical treatment.
      These records were linked to generate a complete picture of each event. Census
      data were used to calculate rates of injury for various population groups.
      RESULTS: A total of 1915 cases of injury due to firearms were identified between
      November 16, 1992, and May 15, 1994. The crude rate of firearm injury per 100,000
      person-years was 222.6 in Memphis, 143.6 in Galveston, and 54.1 in Seattle.
      Approximately 88 percent of the injuries were incurred during confirmed or
      probable assaults; 7 percent were sustained in the course of suicide or attempted
      suicide; unintentional injuries accounted for 4 percent of the cases. Handguns
      were used in 88 percent of the cases in which the type of weapon was recorded.
      Five percent of the 1677 victims who were brought to a hospital emergency
      department could not be resuscitated; 53 percent were hospitalized, and 42
      percent were treated and released. Ninety-seven percent of the deaths occurred
      within 24 hours of the injury. Emergency department and inpatient charges
      exceeded $16.5 million. CONCLUSIONS: Injuries due to firearms, most involving
      handguns, are a major cause of morbidity and mortality in U.S. urban areas. The
      incidence varies greatly from city to city.

PMID- 8875923
TI  - Antimicrobial-drug resistance.

PMID- 8875924
TI  - Genetics in clinical cancer care--the future is now.

PMID- 8875925
TI  - The timing of surgery for severe mitral regurgitation.

PMID- 8875926
TI  - Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of
      53BP2.
AB  - Mutations in the p53 tumor suppressor are among the most frequently observed
      genetic alterations in human cancer and map to the 200-amino acid core domain of
      the protein. The core domain contains the sequence-specific DNA binding activity
      and the in vitro 53BP2 protein binding activity of p53. The crystal structure of
      the p53 core domain bound to the 53BP2 protein, which contains an SH3 (Src
      homology 3) domain and four ankyrin repeats, revealed that (i) the SH3 domain
      binds the L3 loop of p53 in a manner distinct from that of previously
      characterized SH3-polyproline peptide complexes, and (ii) an ankyrin repeat,
      which forms an L-shaped structure consisting of a beta hairpin and two alpha
      helices, binds the L2 loop of p53. The structure of the complex shows that the
      53BP2 binding site on the p53 core domain consists of evolutionarily conserved
      regions that are frequently mutated in cancer and that it overlaps the site of
      DNA binding. The six most frequently observed p53 mutations disrupt 53BP2 binding
      in vitro. The structure provides evidence that the 53BP2-p53 complex forms in
      vivo and may have a critical role in the p53 pathway of tumor suppression.

PMID- 8875927
TI  - U1-mediated exon definition interactions between AT-AC and GT-AG introns.
AB  - A minor class of metazoan introns has well-conserved splice sites with 5'-AU-AC
      3' boundaries, compared to the 5'-GU-AG-3' boundaries and degenerate splice sites
      of conventional introns. Splicing of the AT-AC intron 2 of a sodium channel
      (SCN4A) precursor messenger RNA in vitro did not require inhibition of
      conventional splicing and required adenosine triphosphate, magnesium, and U12
      small nuclear RNA (snRNA). When exon 3 was followed by the 5' splice site from
      the downstream conventional intron, splicing of intron 2 was greatly stimulated.
      This effect was U1 snRNA-dependent, unlike the basal AT-AC splicing reaction.
      Therefore, U1-mediated exon definition interactions can coordinate the activities
      of major and minor spliceosomes.

PMID- 8875928
TI  - Nonstationary Phase of the Plio-Pleistocene Asian Monsoon
AB  - Paleoclimate records indicate that the strength of the Asian summer monsoon is
      sensitive to orbital forcing at the obliquity and precession periods (41,000 and
      23,000 years, respectively) and the extent of Northern Hemisphere glaciation.
      Over the past 2.6 million years, the timing (phase) of strong monsoons has
      changed by approximately 83 degrees in the precession and approximately 124
      degrees in the obliquity bands relative to the phase of maximum global ice volume
      (inferred from the marine oxygen isotope record). These results suggest that one
      or both of these systems is nonstationary relative to orbital forcing.

PMID- 8875930
TI  - Dynamical Instabilities and the Formation of Extrasolar Planetary Systems
AB  - The existence of a dominant massive planet, Jupiter, in our solar system,
      although perhaps essential for long-term dynamical stability and the development
      of life, may not be typical of planetary systems that form around other stars. In
      a system containing two Jupiter-like planets, the possibility exists that a
      dynamical instability will develop. Computer simulations suggest that in many
      cases this instability leads to the ejection of one planet while the other is
      left in a smaller, eccentric orbit. In extreme cases, the eccentric orbit has a
      small enough periastron distance that it may circularize at an orbital period as
      short as a few days through tidal dissipation. This may explain the recently
      detected Jupiter-mass planets in very tight circular orbits and wider eccentric
      orbits around nearby stars.

PMID- 8875929
TI  - Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor
      transactivation domain.
AB  - The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that
      it can bind the transactivation domain of p53 and downregulate its ability to
      activate transcription. In certain cancers, MDM2 amplification is a common event
      and contributes to the inactivation of p53. The crystal structure of the 109
      residue amino-terminal domain of MDM2 bound to a 15-residue transactivation
      domain peptide of p53 revealed that MDM2 has a deep hydrophobic cleft on which
      the p53 peptide binds as an amphipathic alpha helix. The interface relies on the
      steric complementarity between the MDM2 cleft and the hydrophobic face of the p53
      alpha helix and, in particular, on a triad of p53 amino acids-Phe19, Trp23, and
      Leu26-which insert deep into the MDM2 cleft. These same p53 residues are also
      involved in transactivation, supporting the hypothesis that MDM2 inactivates p53
      by concealing its transactivation domain. The structure also suggests that the
      amphipathic alpha helix may be a common structural motif in the binding of a
      diverse family of transactivation factors to the TATA-binding protein-associated
      factors.

PMID- 8875931
TI  - Controlled Deposition of Size-Selected Silver Nanoclusters
AB  - Variable-temperature scanning tunneling microscopy was used to study the effect
      of kinetic cluster energy and rare-gas buffer layers on the deposition process of
      size-selected silver nanoclusters on a platinum(111) surface. Clusters with
      impact energies of </=1 electron volt per atom could be landed nondestructively
      on the bare substrate, whereas at higher kinetic energies fragmentation and
      substrate damage were observed. Clusters with elevated impact energy could be
      soft-landed via an argon buffer layer on the platinum substrate, which
      efficiently dissipated the kinetic energy. Nondestructive cluster deposition
      represents a promising method to produce monodispersed nanostructures at
      surfaces.

PMID- 8875932
TI  - Thermally Switchable Periodicities and Diffraction from Mesoscopically Ordered
      Materials
AB  - Two switchable, mesoscopically periodic materials were created by combining
      crystalline colloidal array (CCA) self-assembly with the temperature-induced
      volume phase transition of poly(N-isopropylacrylamide) (PNIPAM). Body-centered
      cubic CCAs of hydrated, swollen PNIPAM particles Bragg-diffract infrared,
      visible, and ultraviolet light weakly, whereas arrays of compact shrunken
      particles diffract efficiently. A tunable diffracting array was also created by
      embedding a CCA of polystyrene spheres within a PNIPAM hydrogel that swells and
      contracts with temperature; thus the array lattice constant varies with
      temperature, and the diffracted wavelength was thermally tunable across the
      entire visible spectrum. These materials may find applications in many areas of
      optics and materials science.

PMID- 8875933
TI  - Mg/Ca Thermometry in Coral Skeletons
AB  - The magnesium-to-calcium (Mg/Ca) ratio of coral skeletons from Ishigaki Island,
      Ryukyu Islands, Japan, closely tracked sea surface temperature (SST) over an 8
      year period. Measurements were made with the fast technique of inductively
      coupled plasma-atomic emission spectrometry. The variation of the coral Mg/Ca
      ratio with SST change is about four times that of the current, widely used coral
      strontium-to-calcium ratio. The temporal and geographic variation of the seawater
      Mg2+/Ca2+ ratio probably has little influence on coral Mg/Ca variation. Results
      indicate that the coral Mg/Ca ratio has the potential to provide fast, precise,
      high-resolution proxies for past tropical SSTs.

PMID- 8875934
TI  - Anisotropy in the Inner Core: Could It Be Due To Low-Order Convection?
AB  - A recently assembled data set of inner core-sensitive free oscillation splitting
      measurements and body wave differential travel times provides constraints on the
      patterns of anisotropy in the Earth's inner core. Applying a formalism that
      allows departures from radial symmetry and cylindrical anisotropy results in
      models with P-wave velocity distributions whose strength and pattern are
      incompatible with frozen-in anisotropy, but rather suggest a simple large-scale
      convection regime in the inner core.

PMID- 8875935
TI  - Three-dimensional imaging of single molecules solvated in pores of
      poly(acrylamide) gels.
AB  - Individual fluorescent molecules and individual singly labeled proteins were
      observed in the water-filled pores of poly(acrylamide) gels by far-field
      microscopy. Brownian motion was markedly reduced by the gel framework, thus
      enabling extended study of single fluorophores in aqueous environments. A highly
      axially dependent laser field was used both to excite the fluorophores and to
      image the molecules in three dimensions. Single molecules were followed as they
      moved within and through the porous gel structure. In contrast to dry polymeric
      hosts, these water-based gels may form a useful medium for single-molecule
      studies of biological systems in vitro.

PMID- 8875936
TI  - Rate Constants for Charge Transfer Across Semiconductor-Liquid Interfaces
AB  - Interfacial charge-transfer rate constants have been measured for n-type Si
      electrodes in contact with a series of viologen-based redox couples in methanol
      through analyses of the behavior of these junctions with respect to their current
      density versus potential and differential capacitance versus potential
      properties. The data allow evaluation of the maximum rate constant (and therefore
      the electronic coupling) for majority carriers in the solid as well as of the
      dependence of the rate constant on the driving force for transfer of delocalized
      electrons from the n-Si semiconducting electrode into the localized molecular
      redox species in the solution phase. The data are in good agreement with existing
      models of this interfacial electron transfer process and provide insight into the
      fundamental kinetic events underlying the use of semiconducting photoelectrodes
      in applications such as solar energy conversion.

PMID- 8875937
TI  - Maturation of a central glutamatergic synapse.
AB  - Whole-cell recordings from optic tectal neurons in Xenopus tadpoles were used to
      study the maturation of a glutamatergic synapse. The first glutamatergic
      transmission is mediated only by N-methyl-D-aspartate (NMDA) receptors and is
      silent at resting potentials. More mature synapses acquire transmission by alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. This
      maturational program is mimicked by postsynaptic expression of constitutively
      active calcium-calmodulin-dependent protein kinase II (CaMKII). Newly formed
      synapses may be silent unless sufficient depolarization is provided by coincident
      activity that could activate postsynaptic CaMKII, resulting in the appearance of
      AMPA responses.

PMID- 8875938
TI  - Distinct mechanisms for synchronization and temporal patterning of odor-encoding
      neural assemblies.
AB  - Stimulus-evoked oscillatory synchronization of neural assemblies and temporal
      patterns of neuronal activity have been observed in many sensory systems, such as
      the visual and auditory cortices of mammals or the olfactory system of insects.
      In the locust olfactory system, single odor puffs cause the immediate formation
      of odor-specific neural assemblies, defined both by their transient synchronized
      firing and their progressive transformation over the course of a response. The
      application of an antagonist of ionotropic gamma-aminobutyric acid (GABA)
      receptors to the first olfactory relay neuropil selectively blocked the fast
      inhibitory synapse between local and projection neurons. This manipulation
      abolished the synchronization of the odor-coding neural ensembles but did not
      affect each neuron's temporal response patterns to odors, even when these
      patterns contained periods of inhibition. Fast GABA-mediated inhibition,
      therefore, appears to underlie neuronal synchronization but not response tuning
      in this olfactory system. The selective desynchronization of stimulus-evoked
      oscillating neural assemblies in vivo is now possible, enabling direct functional
      tests of their significance for sensation and perception.

PMID- 8875939
TI  - Antibacterial agents that inhibit lipid A biosynthesis.
AB  - Lipid A constitutes the outer monolayer of the outer membrane of Gram-negative
      bacteria and is essential for bacterial growth. Synthetic antibacterials were
      identified that inhibit the second enzyme (a unique deacetylase) of lipid A
      biosynthesis. The inhibitors are chiral hydroxamic acids bearing certain
      hydrophobic aromatic moieties. They may bind to a metal in the active site of the
      deacetylase. The most potent analog (with an inhibition constant of about 50 nM)
      displayed a minimal inhibitory concentration of about 1 microgram per milliliter
      against Escherichia coli, caused three logs of bacterial killing in 4 hours, and
      cured mice infected with a lethal intraperitoneal dose of E. coli.

PMID- 8875940
TI  - CKI1, a histidine kinase homolog implicated in cytokinin signal transduction.
AB  - Although cytokinin plays a central role in plant development, little is known
      about cytokinin signal transduction. Five Arabidopsis thaliana mutants that
      exhibit typical cytokinin responses, including rapid cell division and shoot
      formation in tissue culture in the absence of exogenous cytokinin, were isolated
      by activation transferred DNA tagging. A gene, CKI1, which was tagged in four of
      the five mutants and induced typical cytokinin responses after introduction and
      overexpression in plants, was cloned. CKI1 encodes a protein similar to the two
      component regulators. These results suggest that CKI1 is involved in cytokinin
      signal transduction, possibly as a cytokinin receptor.

PMID- 8875941
TI  - Quantitative image analysis of HIV-1 infection in lymphoid tissue.
AB  - Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular
      level in tissue reservoirs provides opportunities to better understand the
      pathogenesis of infection and to rationally design and monitor therapy. A
      quantitative technique was developed to determine viral burden in two important
      cellular compartments in lymphoid tissues. Image analysis and in situ
      hybridization were combined to show that in the presymptomatic stages of
      infection there is a large, relatively stable pool of virions on the surfaces of
      follicular dendritic cells and a smaller pool of productively infected cells.
      Despite evidence of constraints on HIV-1 replication in the infected cell
      population in lymphoid tissues, estimates of the numbers of these cells and the
      virus they could produce are consistent with the quantities of virus that have
      been detected in the bloodstream. The cellular sources of virus production and
      storage in lymphoid tissues can now be studied with this approach over the course
      of infection and treatment.

PMID- 8875943
TI  - Conditional Manipulation of Sex Ratios by Ant Workers: A Test of Kin Selection
      Theory
AB  - Variable queen mating frequencies provide a unique opportunity to study the
      resolution of worker-queen conflict over sex ratio in social Hymenoptera, because
      the conflict is maximal in colonies headed by a singly mated queen and is weak or
      nonexistent in colonies headed by a multiply mated queen. In the wood ant Formica
      exsecta, workers in colonies with a singly mated queen, but not those in colonies
      with a multiply mated queen, altered the sex ratio of queen-laid eggs by
      eliminating males to preferentially raise queens. By this conditional response to
      queen mating frequency, workers enhance their inclusive fitness.

PMID- 8875942
TI  - Signal transduction by DR3, a death domain-containing receptor related to TNFR-1
      and CD95.
AB  - Tumor necrosis factor receptor-1 (TNFR-1) and CD95 (also called Fas or APO-1) are
      cytokine receptors that engage the apoptosis pathway through a region of
      intracellular homology, designated the "death domain." Another death domain
      containing member of the TNFR family, death receptor 3 (DR3), was identified and
      was shown to induce both apoptosis and activation of nuclear factor kappaB.
      Expression of DR3 appears to be restricted to tissues enriched in lymphocytes.
      DR3 signal transduction is mediated by a complex of intracellular signaling
      molecules including TRADD, TRAF2, FADD, and FLICE. Thus, DR3 likely plays a role
      in regulating lymphocyte homeostasis.

PMID- 8875944
TI  - Hypertension induced in pregnant mice by placental renin and maternal
      angiotensinogen.
AB  - Maternal hypertension is a common complication of pregnancy and its
      pathophysiology is poorly understood. This phenomenon was studied in an animal
      model by mating transgenic mice expressing components of the human renin
      angiotensin system. When transgenic females expressing angiotensinogen were mated
      with transgenic males expressing renin, the pregnant females displayed a
      transient elevation of blood pressure in late pregnancy, due to secretion of
      placental human renin into the maternal circulation. Blood pressure returned to
      normal levels after delivery of the pups. Histopathologic examination revealed
      uniform enlargement of glomeruli associated with an increase in urinary protein
      excretion, myocardial hypertrophy, and necrosis and edema in the placenta. These
      mice may provide molecular insights into pregnancy-associated hypertension in
      humans.

PMID- 8875945
TI  - Laser capture microdissection.
AB  - Laser capture microdissection (LCM) under direct microscopic visualization
      permits rapid one-step procurement of selected human cell populations from a
      section of complex, heterogeneous tissue. In this technique, a transparent
      thermoplastic film (ethylene vinyl acetate polymer) is applied to the surface of
      the tissue section on a standard glass histopathology slide; a carbon dioxide
      laser pulse then specifically activates the film above the cells of interest.
      Strong focal adhesion allows selective procurement of the targeted cells.
      Multiple examples of LCM transfer and tissue analysis, including polymerase chain
      reaction amplification of DNA and RNA, and enzyme recovery from transferred
      tissue are demonstrated.

PMID- 8875946
TI  - Molecular basis of hair growth control.

PMID- 8875947
TI  - Photothermally induced vessel-wall necrosis after pulsed dye laser treatment:
      lack of response in port-wine stains with small sized or deeply located vessels.
AB  - The optimal treatment of port-wine stains is laser-induced selective
      photothermolysis. Lesion color and location and the age of the patient are
      reported to influence the therapeutic outcome. This study was initiated to
      analyze the outcome not only by the clinical response of lightening, but also in
      terms of photothermally induced necrosis to the vessel wall. Punch biopsy
      specimens were taken from 51 patients before treatment. Post-treatment biopsies
      were taken after exposure to a pulsed dye laser (585-nm wavelength, 0.45-ms pulse
      length) with an irradiant fluence of 6.5 J/cm2. Vessel diameter, depth, and wall
      thickness were measured in all histologic slides. The viability of the vessel
      walls was evaluated using an enzyme histochemical method. Port-wine stains with
      good blanching had significantly more superficially located vessels than the
      moderate and poor responders (p < 0.000). The moderate and good responding
      lesions consisted of moderate-sized vessels with diameters of 38 +/- 17
      micrometers and 38 +/- 19 micrometers (mean +/- SD), respectively. The lesions
      showing poor blanching had significantly smaller vessels, with a diameter of 19
      +/- 6.5 micrometers < 0.000). Analyses of the post-treatment specimens showed
      that coagulated vessels were superficially located and of moderate size, whereas
      the viable vessels were small with a median diameter of 14 micrometers. The
      probability of coagulation correlated with the thickness of the vessel wall.
      These data indicate that the therapeutic outcome of port-wine stains can be
      improved by using the lesional vessel parameters to select the optimal laser
      wavelength, pulse duration, and dose.

PMID- 8875948
TI  - Syndecans-1 and -4 are induced during wound repair of neonatal but not fetal
      skin.
AB  - Syndecans are a family of four cell surface proteoglycans that bind to various
      components of the extracellular environment and can regulate many cellular
      behaviors including growth, adhesion, and movement. To determine whether
      syndecans can function during wound repair, we have examined expression of the
      syndecans during wound repair of adult mouse and neonatal or fetal human skin.
      Syndecan-1 and -4 were induced in the dermis within 12 h after incisional injury
      of murine or neonatal human skin. Syndecan-1 was induced primarily on
      endothelium, and syndecan-4 was present throughout the dermis at the site of
      injury. Following re-epithelialization, expression of the syndecans return to
      their baseline level. In marked contrast to these observations, wounded human
      fetal skin showed no increase in expression of syndecans. This lack of increase
      in the expression of syndecans by cells of the dermis correlates with prior
      observations that fetal skin heals without a polymorphonuclear cell infiltrate,
      appreciable fibrosis, or clinically apparent scar. Thus, induced expression of
      syndecans is not an absolute requirement for wound repair but does correlate with
      the occurrence of fibrosis in mature skin. These findings support the role of
      syndecans as regulators of cell behavior and suggest that syndecan-1 and -4
      induction in the dermis may contribute to events that lead to inflammation and
      fibrosis.

PMID- 8875949
TI  - Ex vivo study of skin phototypes.
AB  - We studied skin phototypes ex vivo to validate a model of epidermal
      reconstruction with melanocytes. We made autologous epidermal reconstructs with
      keratinocytes and melanocytes of healthy donors of skin phototypes I to VI.
      Keratinocytes and melanocytes were seeded on a dead de-epidermized dermis
      (Prunieras type) at a 1:20 melanocyte/keratinocyte ratio. Reconstructed epidermis
      was grown for 15 d at the air-liquid interface with or without ultraviolet B
      irradiation. A macroscopic, chromometric. histologic, and ultrastructural
      evaluation was performed. Reconstructs reproduced the initial phototype with few
      modifications. The intensity of melanin transfer correlated with the in vivo
      situation and was stimulated after ultraviolet B irradiation in reconstructs of
      all categories of skin phototypes.

PMID- 8875950
TI  - Regulation of tyrosinase mRNA in mouse melanoma cells by alpha-melanocyte
      stimulating hormone.
AB  - Cloudman S-91 mouse melanoma cells respond to alpha-melanocyte-stimulating
      hormone) by demonstrating a marked increase in tyrosinase activity (O-diphenol-O2
      oxidoreductase, EC 1.14.18.1). This increase is the result of increased levels of
      tyrosinase mRNA with a subsequent increase in tyrosinase abundance. Our studies
      were carried out to determine the effect of melanocyte-stimulating hormone on
      tyrosinase gene transcription and to measure the kinetics of the hormone-induced
      increase in tyrosinase mRNA. When melanoma cells were exposed continuously to
      melanocyte-stimulating hormone for 6 d, a large but transient increase in both
      tyrosinase mRNA abundance and enzyme activity were observed. The maximum increase
      in tyrosinase mRNA occurred 60 h after melanocyte-stimulating hormone stimulation
      and was followed by a decline in message levels even though cells were
      continuously exposed to hormone. Results of nuclear run-off transcription assays
      showed that melanocyte-stimulating hormone caused a slow increase in the rate of
      transcription of the tyrosinase gene with a maximal 6-fold stimulation occurring
      at 48 h. In cells treated with the ribonucleic acid synthesis inhibitor, 5,6
      dichloro-1-beta-D-ribofuranosylbenzimidazole, tyrosinase mRNA levels decayed with
      a half-life of 4-5 h. This decay rate was unaffected by treatment of cells with
      melanocyte-stimulating hormone, indicating that the hormone does not act to
      stabilize tyrosinase ribonucleic acid. Inhibition of protein synthesis by
      treatment with cycloheximide had no effect on the melanocyte-stimulating hormone
      induced increase in tyrosinase messenger ribonucleic acid levels suggesting that
      ongoing protein synthesis is not required for, at least, the initial stimulation
      of tyrosinase gene transcription by melanocyte-stimulating hormone.

PMID- 8875951
TI  - Excess of nevi related to immunodeficiency: a study in HIV-infected patients and
      renal transplant recipients.
AB  - To assess the relationship between immune system and nevi, we studied two models
      of immunodeficiency caused by different mechanisms, i.e., virus and drug. Our
      rationale was that if an excess of nevi was found in these two epidemiologic
      models, it could be concluded that the excess was due to immunodeficiency itself
      rather than its cause. One hundred ten renal transplant recipients (RTR) were
      compared with age-, sex-, and phenotype-matched controls. Eighty four HIV
      positive patients (HIV+) were compared with similarly matched controls. Nevi < 5
      mm (N < 5) or > or = 5 mm (N > or = 5) were counted in three sites representative
      of regularly, intermittently, and never sun-exposed sites. The number of N < 5
      was higher in RTR (p < 0.001) and in HIV+ (p < 0.001) than in respective
      controls. N > or = 5 were significantly higher only in RTR. These differences
      tended to be the same for all sites and persisted after adjustment for possible
      confounding factors. The incidence of atypical nevus was higher in RTR than in
      controls. Immunodeficiency seems to promote the occurrence of nevi. This supports
      the concept of immune surveillance of nevi and raises the question of whether sun
      induced immune suppression plays a role in the development of nevi. As nevi are
      risk markers for melanoma, a higher incidence of melanoma could be expected in
      immunocompromised patients.

PMID- 8875952
TI  - Cysteine deprivation promotes eumelanogenesis in human melanoma cells.
AB  - Melanocytic cells can produce two types of pigment, pheomelanin or eumelanin. We
      used two types of human melanoma cell lines to explore the regulation of
      pigmentation by biochemical and enzymatic studies. These two cell lines were
      previously designated as either pheomelanotic or of mixed type when cultured in a
      medium rich in cysteine. We analyzed the effects of L-cysteine depletion on
      melanin synthesis and the involvement of the tyrosinase-related proteins in the
      production of both eumelanin and pheomelanin. Cultures were exposed to L-cysteine
      concentrations ranging from 206 to 2.06 microM, and the following parameters were
      measured: tyrosine hydroxylase activity, intracellular L-cysteine and glutathione
      concentrations, eumelanin and pheomelanin formation, and tyrosinase-related
      protein-1 and -2 mRNA levels. Extracellular L-cysteine depletion significantly
      increased tyrosine hydroxylase activity and promoted both eumelanogenesis and
      visible pigmentation in both lines. In contrast, pheomelanogenesis was increased
      only in the pheomelanotic cell line. Whereas eumelanogenesis was apparent upon L
      cysteine depletion, tyrosinase-related protein-1 expression was not induced in
      the pheomelanotic cells, and tyrosinase-related protein-2 expression remained
      unchanged. Thus, tyrosinase-related protein-1 mRNA expression seems to be
      concomitant with eumelanogenesis when the L-cysteine concentration is high, but
      does not appear essential for eumelanogenesis at low L-cysteine concentrations.
      The mechanisms governing pheomelanin to eumelanin balance are dependent on L
      cysteine, glutathione, and tyrosinase-related protein-1 expression, but none of
      these factors alone appears to be dominant in directing the synthesis of a
      particular type of melanin.

PMID- 8875953
TI  - Mutations in the ligand-binding domain of the kit receptor: an uncommon site in
      human piebaldism.
AB  - Heterozygous mutations in the gene for the Kit transmembrane receptor have been
      identified recently in human piebaldism and mouse "dominant spotting."
      Interestingly, all of the 14 known missense mutations that cause depigmentation
      in these species map to the tyrosine kinase domain of the receptor, whereas none
      have involved the extracellular ligand-binding domain. In an attempt to detect
      these uncommon mutations, we screened the nine exons encoding the extracellular
      portion of Kit for single-strand conformation polymorphisms (SSCP) in eight
      piebald subjects previously reported to be negative for kinase mutations. Four of
      these eight kindreds proved to carry novel mutations. The first mutation, found
      in two apparently unrelated probands with mild piebaldism and English ancestry,
      substitutes an arginine for a highly conserved cysteine at codon 136. This
      substitution disrupts a putative disulfide bond required for formation of the
      second Ig-like (D2) loop of the Kit ligand-binding domain. The second mutation,
      detected in a piebald kindred characterized by unusually limited depigmentation,
      substitutes a threonine for an alanine at codon 178, a site just proximal to
      conserved cysteines at codons 183 and 186. The third mutation, occurring in a
      kindred with more extensive depigmentation, is a novel four-base insertion in
      exon 2 that results in a proximal frameshift and premature termination. The data
      strongly suggest that piebaldism can result from missense mutations in the Kit
      ligand-binding domain, although the resulting phenotype may be milder than that
      observed for null or kinase mutations. The apparent clustering of these uncommon
      mutations at or near the conserved cysteines for the D2 Ig-like loop further
      suggests a critical role for this region in Kit receptor function.

PMID- 8875954
TI  - Skindex, a quality-of-life measure for patients with skin disease: reliability,
      validity, and responsiveness.
AB  - To measure the effects of skin disease on patients' quality of life, we developed
      a 61-item self-administered survey instrument called Skindex. Skindex has eight
      scales, each of which addresses a construct, or an abstract component, in a
      comprehensive conceptual framework: cognitive effects, social effects,
      depression, fear, embarrassment, anger, physical discomfort, and physical
      limitations. Item responses are standardized from 0 (no effect) to 100 (maximal
      effect); a scale score is the average of responses to items addressing a
      construct. In 201 patients seen by dermatologists, mean scale scores (+/-SD)
      ranged from 14 (+/-17) for physical limitations to 31 (+/-22) for physical
      discomfort. Scale scores were reproducible after 72 h (r = 0.68-0.90) and were
      internally consistent (Cronbach's alpha = 0.76-0.86). Construct validity was
      assessed in two ways: (i) in a comparison of patients with inflammatory
      dermatoses and patients with isolated lesions, patients with inflammatory
      dermatoses had higher scale scores, and (ii) in an exploratory factor analysis,
      78% of the common variance was explained by seven factors that correlated with
      the scale scores of Skindex. Most of the a priori scale scores changed in the
      expected direction in patients who reported that their skin conditions had
      improved or worsened after 6 mo. Finally, physicians' judgments of disease
      severity did not consistently correlate with Skindex scores. These preliminary
      data suggest that Skindex reliably and responsively measures the effects of skin
      disease on patients' quality of life and may supplement clinical judgments of
      disease severity.

PMID- 8875955
TI  - Topical retinaldehyde increases skin content of retinoic acid and exerts biologic
      activity in mouse skin.
AB  - Retinaldehyde, a natural metabolite of beta-carotene and retinol, has been
      proposed recently for topical use in humans. Because retinaldehyde does not bind
      to retinoid nuclear receptors, its biologic activity should result from enzymatic
      transformation by epidermal keratinocytes into ligands for these receptors, such
      as all-trans retinoic acid and 9-cis-retinoic acid. In this study, we analyzed by
      high performance liquid chromatography the type and amounts of tissue retinoids
      as well as several biologic activities resulting from topical application of
      either retinaldehyde or all-trans retinoic acid on mouse tail skin. Biologic
      activities of all-trans retinoic acid and retinaldehyde were qualitatively
      identical in metaplastic parameters (induction of orthokeratosis, reduction of
      keratin 65-kDa mRNA, increase in filaggrin and loricrin mRNAs) and hyperplastic
      parameters (increase in epidermal thickness, increase in bromodeoxyuridine (BrdU)
      positive cells, increase in keratin 50-kDa mRNA, and reduction in keratin 70-kDa
      mRNA). Some quantitative differences, not all in favor of all-trans retinoic
      acid, were found in several indices. Cellular retinoic acid-binding protein II
      and cellular retinol-binding protein I mRNAs were increased by both topical
      retinaldehyde and all-trans retinoic acid. Whereas all-trans retinoic acid, 9-cis
      retinoic acid, and 13-cis-retinoic acid were not detectable (limit 5 ng/g) in
      vehicle-treated skin, 0.05% retinaldehyde-treated skin contained 13 +/- 6.9 ng/g
      wet tissue of all-trans retinoic acid (mean +/- SD), 12.6 +/- 5.9 ng/g 13-cis
      retinoic acid, and no 9-cis-retinoic acid. In contrast, 9-cis-retinoic acid was
      detectable in 0.05% of all-trans retinoic acid-treated skin, which also contained
      25-fold more all-trans retinoic acid and 5-fold more 13-cis-retinoic acid than
      retinaldehyde-treated skin. Our results show that topical retinaldehyde is
      transformed in vivo into all-trans retinoic acid by mouse epidermis. The small
      amounts of ligand for retinoic acid nuclear receptors thus produced are
      sufficient to induce biologic effects similar to those resulting from the topical
      application of the ligand itself in much higher concentration.

PMID- 8875956
TI  - Role of mitochondria in tributyltin-induced interleukin-1alpha production in
      murine keratinocytes.
AB  - Tributyltin (TBT) salts are well known skin irritants in rodents and humans. TBT
      induced both the intracellular production of interleukin-1alpha (IL-1alpha) and
      its release into culture medium in a murine keratinocyte cell line (HEL30). Here,
      we report that mitochondria are important for TBT-induced IL-1alpha production.
      Confluent cells were treated with increasing concentrations of TBT (0--2.5
      microM) or dimethylsulfoxide as vehicle control. At different times thereafter (0
      -24 h), nuclear extracts were analyzed for nuclear factor-(kappa)B (NF-(kappa)B)
      binding activity by electrophoretic mobility shift assay, and the released and
      cell-associated IL-1alpha was measured by enzyme-linked immunosorbent assay. TBT
      induced a direct and concentration-related activation of NF-(kappa)B, which
      peaked at 2 h and was blocked by pyrrolidinedithiocarbamate, a potent NF-(kappa)B
      inhibitor, and rotenone, an inhibitor of the electron entry from complex I to
      ubiquinone. Rotenone also induced a concentration-related inhibition of IL-1alpha
      synthesis induced by TBT, but rotenone did not completely abrogate TBT-induced IL
      1alpha production, which suggests that other transcription factors may be
      involved in IL-1alpha production. Prolonged treatment with ethidium bromide, an
      inhibitor of mitochondrial DNA and RNA synthesis, was used to partially deplete
      cells of functional mitochondria. After 5 d of treatment, mitochondrial
      conversion of tetrazolium bromide to formazan was reduced by 50%, and IL-1alpha
      release was decreased by 65%, whereas no induction of intracellular IL-1alpha was
      observed. This effect was not due to inhibition of protein synthesis, because
      identical incorporation of [3H]leucine into protein in control and ethidium
      bromide-treated cells was identical. This impairment of mitochondrial metabolism
      inhibited NF-(kappa)B activation by TBT. These findings indicate that
      mitochondria may be the source of second messenger molecules important for TBT
      induced IL-1alpha production.

PMID- 8875957
TI  - Prostaglandin H-synthase-2 is the main enzyme involved in the biosynthesis of
      octadecanoids from linoleic acid in human dermal fibroblasts stimulated with
      interleukin-1beta.
AB  - This study was focused on the characterization of the metabolism of linoleic acid
      by human dermal fibroblasts and the effect of interleukin-1 on the biosynthesis
      of octadecanoids. Dermal fibroblasts untreated and treated with recombinant IL
      1beta were incubated with exogenous labeled linoleic acid. A combination of high
      performance liquid chromatography and gas chromatography-mass spectrometry was
      used as the analytic technique. We found that dermal fibroblasts convert linoleic
      acid mainly into 13-hydroxy-9-cis,11-trans-octadecadienoic acid (13-HODE) and 9
      hydroxy-10-trans,12-cis-octadecadienoic acid (9-HODE), 13(S)-HODE and 9(R)-HODE
      being the predominant enantiomers. IL-1beta increased the formation of both 13
      HODE and 9-HODE in a concentration-dependent manner with similar EC50 values as
      for prostanoid formation. This effect of IL-1beta on HODEs formation was
      concomitant with the expression of prostaglandin H-synthase-2. Formation of
      octadecanoids was inhibited in a concentration-dependent manner by
      acetylsalicylic acid and indomethacin. Dexamethasone, actinomycin D, and
      cycloheximide abolished the effect of IL-1beta on HODEs biosynthesis.
      Octadecanoid biosynthetic activity was associated with the microsomal fraction.
      Dermal fibroblasts incorporated [14C]-9-HODE and [14C]-13-HODE into
      phospholipids, mainly into phosphatidylcholine. IL-1beta increased significantly
      the esterification of 13-HODE in all glycerophospholipids, the major increase
      being observed in phosphatidylinositol. These results indicate that prostaglandin
      H-synthase-2 is the enzyme responsible for the increase in the ability to form
      HODEs of dermal fibroblasts stimulated with IL-1beta.

PMID- 8875958
TI  - 8-hydroxy-2'-deoxyguanosine is increased in epidermal cells of hairless mice
      after chronic ultraviolet B exposure.
AB  - 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a mutation-prone (G:C to T:A
      transversion) DNA base-modified product generated by reactive oxygen species or
      photodynamic action. G:C to T:A transversions are observed in the p53 and ras
      genes of UVB-induced skin cancers of mice and in squamous and basal cell
      carcinomas of human skin exposed to sunlight. In the current study, 8-OHdG
      formation was evaluated in the epidermis of hairless mice after repeated exposure
      to UVB, and possible mechanisms involved were studied. Exposure of hairless mice
      to either 3.4 [2 minimal erythema dose (MED)] or 16.8 (10 MED) kJ/m2 of UVB three
      times a week for 2 wk induced a 2.5- or 6.1-fold increase, respectively, in the
      levels of 8-OHdG in DNA, compared to the unexposed controls. An
      immunohistochemical method using a monoclonal antibody specific for 8-OHdG showed
      stronger and more extensive staining in the nuclei of UV-irradiated epidermal
      cells than in those of nonirradiated cells. Western blots probed with antibodies
      against 4-hydroxy-2-nonenal-modified proteins confirmed the involvement of
      reactive oxygen species in the epidermal damage induced by chronic UVB exposure.
      3-Nitro-L-tyrosine was detected in western blots in a concentration-dependent
      manner, suggesting that peroxynitrite derived from the reaction of nitric oxide
      and superoxide, both of which were probably released from inflammatory cells, was
      involved in modifying the DNA bases. Therefore, the formation of 8-OHdG after UVB
      exposure appears to be regulated by at least three pathways: photodynamic action,
      lipid peroxidation, and inflammation and may play a role in sunlight-induced skin
      carcinogenesis.

PMID- 8875959
TI  - Functional roles for granzymes in murine epidermal gamma(delta) T-cell-mediated
      killing of tumor targets.
AB  - Granzymes, a family of serine proteases contained in cytoplasmic granules of
      cytotoxic T lymphocytes and natural killer cells, play a critical role in killing
      tumor targets by triggering rapid breakdown of DNA and subsequent apoptosis. We
      have reported previously that dendritic epidermal T cells, which are skin
      specific members of the tissue-type gamma(delta) T-cell family in mice, are
      capable of killing selected tumor cell lines. Here we report that short-term
      cultured dendritic epidermal T-cell lines contain significant N-alpha
      benzyloxycarbonyl-L-Lys-thiobenzyl esterase activity, produce granzyme A protein,
      and express constitutively mRNA for granzymes A and B. Messenger RNA expression
      for granzyme B was also confirmed in freshly procured Thy-1+ epidermal cells
      (i.e., dendritic epidermal T cells). Finally, preincubation of dendritic
      epidermal T cell lines with a granzyme inhibitor, dichloroisocoumarin, but not
      with a cysteine protease inhibitor, E-64, abrogated completely their capacity to
      trigger DNA breakdown in YAC-1 target cells. These results reinforce the concept
      that dendritic epidermal T cells represent skin-resident killer cells that share
      several functional properties with conventional killer leukocytes, thereby
      playing a local immunosurveillance role against tumor development.

PMID- 8875960
TI  - Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase
      levels and activity compared to surgical wound fluids.
AB  - Fluid from acute surgical wounds and from nonhealing pressure ulcers was examined
      for the presence of several matrix metalloproteinases. Gelatin zymography
      demonstrated the presence of two major gelatinases with apparent molecular masses
      of 72 kDa and 92 kDa and two minor gelatinases with apparent mobilities of 68 kDa
      and 125 kDa. Antigen-specific sera identified the 72-kDa protein as matrix
      melloproteinase-2. The same sera also reacted with the 68-kDa protein, which is
      consistent with it being an activated form of matrix metalloproteinase-2. Antigen
      specific sera identified the 92-kDa and 125-kDa proteins as matrix
      metalloproteinase-9. Levels of matrix metalloproteinase-2 and matrix
      metalloproteinase-9 were elevated more than 10-fold and 25-fold, respectively, in
      fluids from pressure ulcers compared with fluids from healing wounds. Examination
      of total potential and actual collagenolytic activity revealed that fluid from
      pressure ulcers contained significantly greater levels of both total and active
      collagenase compared with that of acute surgical wounds. In addition, an enzyme
      linked immunosorbent assay demonstrated that fluids from pressure ulcers
      contained significantly more collagenase complexed with the inhibitor, tissue
      inhibitor of metalloproteinases. Together, these observations suggest that an
      imbalance exists between levels of matrix metalloproteinases and their inhibitors
      in the fluids of pressure ulcers and that this is primarily the result of
      elevated levels of the matrix metalloproteinases. The presence of excessive
      levels of activated forms of matrix-degrading enzymes at the wound surface of
      pressure ulcers may impede the healing of these wounds and may be relevant to the
      development of new rationales for treatment.

PMID- 8875961
TI  - Thapsigargin induces phosphorylation of the 27-kDa heat shock protein in human
      keratinocytes.
AB  - In the human keratinocyte line HaCaT, the nonphosphorylated 27-kDa heat shock
      protein (HSP27) isoform A (pI 6.5) is constitutively expressed. Application of
      thapsigargin, which inhibits Ca2+-ATPase in the endoplasmic reticulum, results in
      the rapid formation of the phosphorylated HSP27 isoform B (pI 6.0) and reduction
      of HSP27 A without affecting the synthesis of HSP27. The thapsigargin-dependent
      HSP27 isoform change is similar to that induced by 43 degrees C heat shock, but
      different from that induced by arsenite, where the biphosphorylated isoform HSP27
      C (pI 5.7) is observed. The receptor agonist bradykinin, which increases
      intracellular Ca2+ (Ca(i)) level, shows no effect on the distribution of HSP27
      isoforms. The responses of HSP27 isoforms to thapsigargin are independent of
      Ca(i) concentration in HaCaT cells. These observations suggest that the
      thapsigargin-induced change in HSP27 isoforms is dependent on the depletion of
      internal Ca2+ stores rather than on the increase in Ca(i) concentration. The
      thapsigargin-induced change in HSP27 isoforms is reduced by the tyrosine kinase
      inhibitor, genistein, but not the protein kinase C inhibitor, H-7. We propose
      that the modulation of HSP27 phosphorylation status by Ca(i) homeostasis may be
      mechanistically linked to control of keratinocyte growth and differentiation and
      responses of keratinocytes to extracellular stresses.

PMID- 8875962
TI  - Temporal correlation between UV radiation locally-inducible tolerance and the
      sequential appearance of dermal, then epidermal, class II MHC+CD11b+
      monocytic/macrophagic cells.
AB  - We performed a time course study in order to define the in vivo relationship
      between the induction of active suppression of contact sensitization and the
      presence of various cells in ultraviolet-exposed dermis and epidermis implicated
      in locally inducible immune tolerance: class II major histocompatibility complex
      (MHC)+CD11b(lo)Gr-1- Langerhans cells (LC), class II MHC-CD45+CD3+ dendritic
      epidermal T cells, class II MHC+CD11b+Gr-1- monocytes or class II MHC+CD11b+Gr-1+
      monocytic/macrophagic cells. Partial tolerance (50%) was first detectable 6 h
      after a single 72 mJ/cm2 ultraviolet B exposure and maximum tolerance at 48 h
      post-ultraviolet exposure. By flow cytometry, a low granularity LC subset had
      disappeared from the epidermis within 6 h after ultraviolet exposure, followed by
      a slower decrease in the high granularity Langerhans cells subset. Within the
      dermis at the 6-h time point, small numbers of infiltrating monocytic/macrophagic
      cells are already apparent. By 24 h post-ultraviolet exposure, at which time
      tolerance has increased to 70%, the infiltrating monocytic/macrophagic population
      had risen to 1.2% of the total dermal cell population and was observed for the
      first time in the epidermis along with other infiltrating leukocytes (i.e.,
      polymorphonuclear leukocytes). By 48 h post-ultraviolet exposure, when a state of
      maximum tolerance is obtained, both constitutive epidermal and dermal antigen
      presenting cell populations were at or near their nadir of depletion. The
      infiltrating monocyte/macrophage population, however, exhibited a dramatic
      increase in the epidermis at 48 and 72 h. Thus, the ability to locally induce a
      state of in vivo tolerance is closely associated with the expansion of class II
      MHC+CD11b+Gr-1+ and -monocytic/macrophagic cells in the dermis and epidermis.

PMID- 8875963
TI  - Effects of keratin 14 ablation on the clinical and cellular phenotype in a
      kindred with recessive epidermolysis bullosa simplex.
AB  - We studied a kindred with recessive epidermolysis bullosa simplex in which the
      affected members lacked expression of the basal cell keratin 14. The patients had
      severe generalized skin blistering that improved slightly with age. The basal
      cells of the patients did not express keratin 14 and contained no keratin
      intermediate filaments. The expression of keratin 5, the obligate copolymer of
      keratin 14, was slightly reduced. The expression of keratin 15, the alternative
      basal cell keratin, was increased, suggesting upregulation or stabilization to
      compensate for the lack of keratin 14. The expression of keratin 16, keratin 17,
      and keratin 19 in the patient's skin was not different from controls.
      Immunoelectron microscopy showed a loose network of keratin 5/keratin 15
      protofilaments in the basal cells. Keratin 15 filaments did not aggregate into
      higher order bundles. Sequence analysis of genomic DNA revealed a homozygous
      mutation in the 3'-acceptor splice site of intron 1 (1840 A-->C) in the affected
      individuals. This mutation led to the skipping of exon 2 in 24% of the KRT14
      transcripts and to the use of a cryptic splice site in 76% of the transcripts.
      Premature termination codons were generated in all transcripts (codons 175+1 or
      175+29), leading to a truncated keratin 14 protein within the helical 1B rod
      domain. The disorder was associated with circumscribed hyperkeratotic lesions
      with the histology of epidermolytic hyperkeratosis. The prognosis of keratin 14
      ablation is much better in the human than in the mouse.

PMID- 8875964
TI  - Involvement of platelet-derived growth factor receptor-alpha in hair canal
      formation.
AB  - Hair follicles develop and are maintained by multiple rounds of inductive events
      involving interactions among various cell types within the follicles and the
      adjacent mesenchyme. Although evidence suggests that several growth factors, cell
      adhesion molecules, and transcriptional regulators are involved in those cell
      cell interactions, the molecular mechanisms regulating each pivotal step of hair
      follicle development, such as formation of the hair germ, root sheath, sebaceous
      gland, and hair canal, remain largely unknown. In this study, we established the
      antagonistic monoclonal antibody APA5 against platelet-derived growth factor
      (PDGF) receptor-alpha (PDGFR-alpha) and used it to investigate the role of PDGFR
      alpha in neonatal skin development. In addition to the dermal mesenchyme, a known
      site of PDGFR-alpha expression, immunohistologic staining of neonatal skin
      detected transient expression of PDGFR-alpha in the perinatal epidermis for
      several days. On the other hand, ligands for PDGFR-alpha were detected in
      epithelial cells and sebaceous glands of hair follicles. To determine whether
      this contiguous expression of PDGF and PDGFR-alpha in neonatal skin plays a
      functional role, we injected APA5 into neonates to block the function of PDGFR
      alpha. Consistent with the PDGF/PDGFR-alpha expression in the neonatal skin, two
      defects were induced by this procedure. First, hair canal formation in the
      epidermis was severely suppressed. Second, the growth of dermal connective
      tissues and of hair follicles of pelage hairs was suppressed. These results
      indicate that PDGF signals are involved in both the epidermis-follicle
      interaction and the dermal mesenchyme-follicle interaction required for hair
      canal formation and the growth of the dermal mesenchyme, respectively.

PMID- 8875966
TI  - HTLV-I and CTCL: the link is missing.

PMID- 8875965
TI  - Differential expression of GRO-alpha and IL-8 mRNA in psoriasis: a model for
      neutrophil migration and accumulation in vivo.
AB  - Dense focal accumulation of neutrophils in the upper epidermis is a hallmark of
      psoriasis. Because the signals for neutrophil diapedesis and migration in vivo
      are not fully understood, psoriatic lesions with pronounced migration of
      neutrophils may serve as an important model for studying neutrophil chemotaxis.
      In this study, we present evidence for differential expression of the neutrophil
      chemotactic cytokines growth-related oncogene alpha, interleukin-8, and ENA-78
      (epithelial cell derived and neutrophil-activating properties, 78 amino acids) in
      psoriatic lesions. In situ hybridization and immunohistochemistry of serial
      sections were employed to identify and microanatomically localize the cells
      producing these chemokines. High levels of focal interleukin-8 message were found
      to be expressed in the upper epidermis by keratinocytes and, most importantly,
      neutrophils themselves. Growth-related oncogene alpha transcripts were detected
      in clusters of keratinocytes of the upper epidermis at the same sites where
      interleukin-8 mRNA was abundant. In contrast to interleukin-8, growth-related
      oncogene alpha was also detected in the papillary dermis produced by vessel
      associated cells. Sites of interleukin-8 and growth-related oncogene alpha mRNA
      expression were associated with infiltration of neutrophils. Interestingly, mRNA
      expression of the highly homologous chemokine ENA-78 was quiescent. In
      conclusion, our data indicate that growth-related oncogene alpha is an important
      chemoattractant for neutrophil diapedesis in vivo, whereas further migration of
      neutrophils and formation of micropustules appears to be influenced by the
      cooperative action of both growth-related oncogene alpha and interleukin-8.

PMID- 8875967
TI  - Symposium on Epidermolysis Bullosa: Molecular Genetics of the Cutaneous Basement
      Membrane Zone, Jefferson Medical College, Philadelphia, Pennsylvania, April 29
      and 30, 1996.

PMID- 8875968
TI  - Current concepts in the management of hypercholesterolemia with an update on
      fluvastatin. Introduction.

PMID- 8875969
TI  - Rationale for effective treatment of hypercholesterolemia.
AB  - The primary objective of treating hypercholesterolemia is to reduce the patient's
      risk of developing coronary artery disease (CAD). Reducing low-density
      lipoprotein (LDL) cholesterol levels to achieve National Cholesterol Education
      Program (NCEP) goal lipid levels greatly reduces this risk. Treatment of
      additional risk factors for CAD (high blood pressure, diabetes, smoking) should
      be addressed and modified as part of appropriate patient management, but a high
      LDL cholesterol level is a major risk factor. Therefore, to effectively modify
      morbidity and mortality, reaching and maintaining NCEP target lipid levels should
      be the goal of lipid-lowering therapy. Epidemiologic data indicate that most
      adults in the United States need <30% reduction in LDL cholesterol level to
      achieve their NCEP goal. Regardless of the intervention or therapeutic agent
      used, the results of numerous studies have demonstrated that reducing LDL
      cholesterol levels to NCEP goals will result in significant reduction of CAD
      risk.

PMID- 8875970
TI  - Review of the major intervention trials of lowering coronary artery disease risk
      through cholesterol reduction.
AB  - Results of primary and secondary prevention trials have shown that lowering total
      cholesterol and low-density lipoprotein (LDL) cholesterol leads to a reduction in
      both fatal and nonfatal ischemic events. The reduced coronary artery disease
      (CAD) risk associated with cholesterol lowering appears to be unrelated to the
      intervention used, whether it be a low-fat/low-cholesterol diet, partial ileal
      bypass surgery, or pharmacologic intervention with an agent such as a bile resin,
      a fibrate, or niacin. Data emerging on the 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitors have shown that this newest class of cholesterol
      lowering agents also reduces the risk for CAD. The studies provide increasing
      evidence that high LDL cholesterol levels not only contribute to atherosclerotic
      plaque formation but also interfere with normal endothelial control of arterial
      vasomotor tone. Because the small amount of plaque regression observed on
      angiographic studies is not sufficient to explain the magnitude of CAD risk
      reduction associated with lowered levels of LDL cholesterol, these studies
      suggest that vasomotor control and plaque stabilization may have a greater impact
      on clinical events than the stenosis caused by atherosclerotic plaques.

PMID- 8875971
TI  - A review of current clinical findings with fluvastatin.
AB  - Fluvastatin, the newest member of the class of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors, is structurally different from the
      fungal metabolites (lovastatin, pravastatin, and simvastatin) and is wholly
      synthetic. Fluvastatin has a distinct biopharmaceutical profile, including a
      short systemic exposure time (half-life of 1.2 hours) and virtually no active
      circulating metabolites. Fluvastatin is targeted to the liver, where it is
      rapidly metabolized; 98% of fluvastatin is protein bound. Double-blind, placebo
      controlled studies have demonstrated that fluvastatin at daily dosages of 20-40
      mg produces significant decreases from baseline in low-density lipoprotein (LDL)
      cholesterol on the order of 22-31% in patients with severe primary
      hypercholesterolemia (mean baseline LDL cholesterol 227 mg/dL) and decreases of
      19-25% in patients with familial hypercholesterolemia (mean baseline LDL
      cholesterol 270 mg/dL). Interim results of a titrate-to-goal, 20-week study in
      patients with moderate hypercholesterolemia (LDL cholesterol >= 160 mg/dL and
      triglycerides <= 350 mg/dL) demonstrate that fluvastatin, 20 mg/day, lowers LDL
      cholesterol by 21% within 6 weeks. Long-term results indicate that the lipid
      lowering effects of fluvastatin are sustained for 96 weeks. Further, 1 study has
      shown that the combination of low-dose fluvastatin plus niacin decreased LDL
      cholesterol levels 40% without untoward adverse events, suggesting that this
      combination is effective and safe for patients needing intensive lipid-lowering
      therapy. Asymptomatic, reversible increases in hepatic transaminase levels occur
      in fluvastatin-treated patients at a frequency comparable to that reported for
      other HMG-CoA reductase inhibitors. The 20-30% reduction in LDL cholesterol
      required by the majority of patients with hypercholesterolemia can be achieved
      with fluvastatin at 20 or 40 mg/day as well as with the other available HMG-CoA
      reductase inhibitors at their most commonly prescribed doses. Fluvastatin, priced
      40% lower than other statins, provides the most cost-effective means of safely
      achieving goal LDL cholesterol levels in these patients.

PMID- 8875972
TI  - Meeting national cholesterol education goals in clinical practice--a comparison
      of lovastatin and fluvastatin in primary prevention.
AB  - The available clinical data for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase inhibitors demonstrate their efficacy and safety in treating
      hypercholesterolemia and improving long-term morbidity and mortality related to
      coronary artery disease. Comparative studies among agents in this class support
      the general perception that, at the most commonly prescribed doses, all these
      drugs reduce low-density lipoprotein (LDL) cholesterol levels by about 20-30%.
      The primary measure of efficacy in the current study was the percentage of
      patients achieving goal levels for LDL cholesterol of < 160 mg/dL, as proposed by
      the National Cholesterol Education Program (NCEP). This study compares the most
      widely prescribed agent in this class, lovastatin, with the newest agent,
      fluvastatin. Patients enrolled had previously been satisfactorily treated with
      lovastatin 20 mg every evening. Following a placebo washout period, patients were
      randomized to receive lovastatin 20 mg with the evening meal (69 patients) or
      fluvastatin 20 mg at bedtime (68 patients) for 4 weeks of open-label therapy. In
      a second 4-week period, patients on lovastatin continued on the initial dosage
      while patients receiving fluvastatin had their daily dosage increased to 40 mg at
      bedtime to evaluate the range of efficacy from 20-40 mg/day. In both treatment
      arms, the majority of patients achieved the goal lipid level. Approximately 85%
      of patients on fluvastatin 20 mg and 90% of patients on lovastatin 20 mg achieved
      the goal within 4 weeks. This small difference was not statistically significant.
      Increasing the dosage to 40 mg at bedtime in the fluvastatin arm produced goal
      LDL cholesterol levels in about 90% of patients. Both agents were well tolerated;
      no patients discontinued therapy because of adverse events.

PMID- 8875973
TI  - Cost-effectiveness of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitor therapy in the managed care era.
AB  - More than $100 billion is spent in the United States each year on cardiovascular
      disease, primarily for hospitalizations and revascularization procedures. This is
      more than for any other disease state. As the clinical practice of medicine
      shifts from the paradigm of private practice to the managed care environment,
      cost-effectiveness is becoming increasingly important. A primary measure in
      analyzing cost-effectiveness is the cost-effectiveness ratio, or the dollar cost
      per unit of improvement for a given expenditure. This measure allows healthcare
      planners to compare completely different interventions. With approximately 52
      million adult U.S. citizens having elevated low-density lipoprotein (LDL)
      cholesterol levels, lipid-lowering therapy---with diet or 3-hydroxy
      3methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors---is an important
      consideration for primary care physicians and managed care providers. The
      National Health and Nutrition Examination Survey (NHANES) III indicates that 75
      88% of adults who have coronary artery disease (CAD) risk factors or CAD require
      only a moderate (20--30%) reduction in LDL cholesterol levels to reach National
      Cholesterol Education Program goals. The clinical literature shows that all 4 of
      the currently available HMG-CoA reductase inhibitors can provide appropriate,
      moderate LDL cholesterol reductions within their recommended dosage ranges. For
      the majority of patients who need a 20--30% reduction in LDL cholesterol,
      fluvastatin 20 or 40 mg once daily provides the most cost-effective HMG-CoA
      therapy, expressed as cost of therapy per 1% LDL cholesterol reduction. For
      patients who need a >30% LDL cholesterol reduction, a high-dose HMG-CoA reductase
      inhibitor (e.g., simvastatin 20 or 40 mg/day) or a combination of a lower-dose
      HMG-CoA reductase inhibitor and a bile acid resin is the preferred initial
      therapy. Although a true cost-effectiveness analysis would incorporate morbidity
      and mortality data from clinical trials, analysis using intermediate endpoints,
      such as LDL cholesterol reduction, suggests that fluvastatin is the preferred
      initial HMG-CoA reductase inhibitor for the treatment of moderate hyperlipidemia.

PMID- 8875974
TI  - Rel/NF-kappaB/IkappaB proteins and cancer.

PMID- 8875975
TI  - Proline-rich sequences mediate the interaction of the Arg protein tyrosine kinase
      with Crk.
AB  - Arg is a ubiquitously expressed member of the Abelson family of nonreceptor
      protein-tyrosine kinases. Defining the Arg sequences that mediate its interaction
      with other proteins is essential to elucidating its role in cellular signaling.
      In this report we demonstrate that Arg associates with c-Crk, an adaptor protein
      composed of an SH2 domain and two SH3 domains, and examine the molecular
      mechanism of the interaction. In vitro experiments revealed that three proline
      rich sequences with distinct specificities for SH3 domains are located in the Arg
      C-terminal domain, just C-terminal to the kinase domain, and that two of these
      sequences bind to the Crk N-terminal SH3 domain. These two sequences conform to
      the PxLPxK/R motif that has been observed in other proteins that bind the Crk N
      terminal SH3 domain. The interaction of Arg with c-Crk in living cells was
      confirmed by the detection of coimmunoprecipitation in coinfected Sf9 cells. In
      addition, increased phosphorylation of c-Crk was observed in cotransfected COS
      cells, indicating that Crk is an Arg substrate. The site of c-Crk phosphorylation
      by Arg was identified as tyrosine 221, a residue whose modification has been
      shown to result in an intramolecular SH2 interaction and a folded conformation.
      These experiments extend the known Arg protein interacting motifs to include SH3
      binding sites and suggest that Arg may function as an effector as well as a
      regulator of Crk activity.

PMID- 8875976
TI  - p53 N-terminus-targeted protein kinase activity is stimulated in response to wild
      type p53 and DNA damage.
AB  - The p53 tumour suppressor protein plays a central role in the cellular defence
      against agents which cause genetic damage. The activity of p53 is regulated at
      different levels and is subject to multi-site phosphorylation by a variety of
      different protein kinases. In this paper we have characterised p53 N-terminus
      targeted protein kinase (p53NK) activities, present in a range of cell lines,
      following fractionation of cellular lysates by ion exchange chromatography on
      HiTrap Q and Mono Q resins. Three peaks of p53NK activity were observed following
      fractionation of HeLa cell lysates; these activities were each able to catalyse
      phosphorylation of up to three residues (serines 4, 6 and 9 in murine p53) within
      the N-terminus of the p53 protein. Similarly, multiple p53NK activities were
      detected in the MethAp53(ts) cell line (which expresses the valine 135
      temperature-sensitive p53 protein). Strikingly, when these cells were shifted
      from 38 degrees C (the non-permissive temperature) to 28 degrees C, at which the
      p53 adopts a wild type conformation, a fivefold stimulation of kinase activity
      was detected. Moreover, when the DNA damage-inducing drugs etoposide or
      camptothecin were added to the cells, a further stimulation of kinase activity
      was observed following growth at 28 degrees C, but not 38 degrees C. These data
      are consistent with a regulatory model in which p53 is sensitive to stress or DNA
      damage through phosphorylation at its N-terminus.

PMID- 8875977
TI  - Effects of ectopic overexpression of p21(WAF1/CIP1) on aneuploidy and the
      malignant phenotype of human brain tumor cells.
AB  - p21WAF1/CIP1 is a downstream effector of the p53 tumor suppressor gene and a
      universal cyclin-dependent kinase (CDK) inhibitor. To determine the ability of
      p21WAF1/CIP1 to function as a tumor suppressor, we constructed a replication
      defective adenovirus vector containing p21WAF1/CIP1 (Adp21WAF1/CIP1) to effect
      ectopic overexpression in a p53-defective human astrocytoma cell line, U-373MG.
      We observed a marked decrease in CDC2 and CDK2 kinase activity associated with a
      corresponding decrease in the amount of CDC2 but not CDK2 protein; a decreased
      growth potential of Adp21WAF1/CIP1-infected cells demonstrated by diminished
      [3H]thymidine incorporation, increased cell doubling time and G1-arrested cell
      cycle; an association between Adp21WAF1/CIP1-infected cells and inhibition of
      aneuploid cell accumulation; and an alteration of the malignant phenotype of
      cells was evidenced by the loss of anchorage-independent growth in soft agar and
      the failure to induce tumorigenesis in both peripheral and intracerebral
      xenograft models, including the prevention of tumor formation Adp21WAF1/CIP1
      infection 2 days post tumor cell implantation. Adp21WAF1/CIP1. Adp21WAF1/CIP1
      appears to be a strong candidate for gene therapy studies based on these studies
      indicating that Adp21WAF1/CIP1 inhibits proliferation, tumorigenicity and
      aneuploidy in human brain tumor cells.

PMID- 8875978
TI  - Inhibition of intratracheal lung cancer development by systemic delivery of E1A.
AB  - Amplification or overexpression of HER-2/neu in human lung cancer has been
      correlated with poor prognosis and chemoresistance. We have previously reported
      that the adenovirus type 5 early region 1A (E1A) gene product can suppress HER
      2/neu-mediated transformation phenotypes through inhibition of HER-2/neu
      expression. To find an efficient way to treat HER-2/neu-overexpressing lung
      cancer with E1A, a replication-deficient adenovirus containing the E1A gene,
      Ad.E1A(+), was used to transduce E1A into HER-2/neu-overexpressing and low
      expressing human lung cancer cell lines. Tumour cell growth in vitro and colony
      formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction in HER
      2/neu-overexpressing lung cancer cell lines. In HER-2/neu low expressing cell
      lines, E1A could not inhibit cell growth in vitro but could reduce the colony
      formation ability in soft agarose, indicating different effects of E1A in these
      two types of cancer cells. To test the therapeutic efficacy of E1A to lung cancer
      by systemic delivery in vivo, tumor-bearing mice were established by
      intratracheal injection of lung cancer cells and treated by i.v. tail injections
      of Ad.E1A(+). As a result, Ad.E1A(+) suppressed HER-2/neu overexpression and
      inhibited intratracheal lung cancer growth. However, no significant tumor
      suppression effect of Ad.E1A(+) was observed in mice bearing HER-2/neu low
      expressing cell line when the same therapeutic procedure was followed. Thus, we
      conclude that systemic delivery of Ad.E1A(+) can efficiently achieve therapeutic
      effect in HER-2/neu-overexpressing lung cancer in vivo.

PMID- 8875979
TI  - Epstein-Barr virus exploits the normal cell pathway to regulate Rb activity
      during the immortalisation of primary B-cells.
AB  - Infection of human primary B-lymphocytes with Epstein-Barr virus (EBV) drives
      quiescent cells into continual proliferation and results in the outgrowth of
      immortal cell lines. This requires re-programming of the mechanisms that, in the
      absence of appropriate antigenic stimulation, normally prevent the proliferation
      of B-lymphocytes. Since the Retinoblastoma protein (pRb) and its relatives, p107
      and p130, play critical roles in controlling the mammalian cell division cycle,
      we have investigated the expression and phosphorylation status of these proteins
      following EBV immortalisation of primary B-lymphocytes. In this report, we show
      that EBV drives the hyperphosphorylation of pRb. This is achieved by a strategy
      involving the altered expression of several components of the signal transduction
      pathway that normally regulates the phosphorylation status of pRb, including the
      up regulation of a number of cyclins and cyclin-dependent kinases and the down
      regulation of a subset of cyclin-dependent kinase inhibitors. The net result is
      the formation of active cyclin-dependent kinase complexes that are capable of
      phosphorylating and inactivating pRb. The results presented here identify the
      activation of a normal signal transduction pathway as an important component of
      the strategy used by EBV to drive cell proliferation.

PMID- 8875981
TI  - Constitutive expression of the Wilms tumor suppressor gene WT1 in F9 embryonal
      carcinoma cells induces apoptotic cell death in response to retinoic acid.
AB  - The product of the Wilms tumor suppressor gene, WT1, is thought to be a tissue
      specific transcription factor regulating cell growth and differentiation. To
      elucidate the function of WT1 in cellular differentiation, we examined the
      changes in the level of WT1 expression during retinoic acid induced
      differentiation of embryonal carcinoma F9 cells into parietal endoderm cells. We
      found that, in response to retinoic acid addition, the expression of WT1
      increased significantly after 12--24 h of incubation, then decreased and finally
      disappeared after 4 days, by which time most of the cells had differentiated into
      primitive endoderm cells. To examine the significance of these changes in WT1
      expression, we established cell lines constitutively expressing one of the WT1
      splicing variants. These cell lines showed a phenotype very similar to parental
      F9 cells in the absence of retinoic acid. However, in the presence of retinoic
      acid, they failed to differentiate into primitive endoderm cells and underwent
      apoptotic death 36 h after the addition of retinoic acid. These results suggest
      that downregulation of WT1 expression is necessary for normal differentiation of
      F9 cells into parietal endoderm cells.

PMID- 8875980
TI  - Chromosome end-to-end associations and telomerase activity during cancer
      progression in human cells after treatment with alpha-particles simulating radon
      progeny.
AB  - Chromosome end-to-end associations seen at metaphase involve telomeres and are
      commonly observed in cells derived from individuals with ataxia telangiectasia
      and most types of human tumors. The associations may arise because of short
      telomeres and/or alterations of chromatin structure. There is a growing consensus
      that telomere length is stabilized by the activity of telomerase in immortal
      cells; however, it is not clear why some immortal cells display chromosome end-to
      end associations. In the present study we evaluated chromosome end-to-end
      associations, telomere length and telomerase activity with the tumorigenic status
      of human bronchial epithelial cells immortalized with human papillomavirus.
      Oncogenic transformation was initiated using radon simulated alpha-particles and
      cells evaluated as primary, secondary and metastatic transformants. The fewest
      chromosome end associations and lowest telomerase activity were observed in the
      parental immortalized cells. However, increased levels of telomerase activity
      were detected in alpha-particle survivors while robust telomerase activity was
      seen in the tumorigenic cell lines. The tumorigenic cells that were telomerase
      positive and had the highest frequency of cells with chromosome end-to-end
      associations were also metastatic. No correlation was found between telomere
      length and the different stages of carcinogenicity.

PMID- 8875982
TI  - The product of the v-src-inducible gene nr-13 is a potent anti-apoptotic factor.
AB  - Tumorigenesis can be induced either by activating cell proliferation or by
      inhibiting metabolic pathways regulating programmed cell death (apoptosis). There
      is evidence suggesting that p60(v-src) and other tyrosine kinases protect cells
      against apoptosis. This effect could contribute to cell transformation by the
      Rous sarcoma virus. Mechanism of cell death inhibition by p60(v-src) remains
      largely unknown. We have recently reported that in avian cells p60(v-src)
      activates the expression of nr-13, a bcl-2-related gene. In this paper, we
      demonstrate, using the bone marrow derived cell line Baf-3 as an experimental
      model, that the product of this avian gene (nr-13) is a potent anti-apoptotic
      factor. In addition, we report that, in quail neuroretinal cells, nr-13
      expression is activated upon infection by the Rous sarcoma virus (RSV) but not by
      other oncogenic retroviruses like FSV or MH2, suggesting that nr-13 is a specific
      target of v-src. Activation of nr-13 expression may be a key step in cellular
      transformation by v-src.

PMID- 8875983
TI  - Human cyclin B1 is targeted to the nucleus in G1 phase prior to its accumulation
      in the cytoplasm.
AB  - The immunolocalisation patterns of cyclin B1 have been investigated in various
      tumour-derived and untransformed human cells, using one polyclonal (B7/B8) and
      two different monoclonal anti-human cyclin B1 antibodies, GNS1 and GNS11. In
      actively dividing cell populations, GNS11 reveals uniquely a cytoplasmic pool of
      cyclin B1 that rapidly increases after the onset of S phase; yet, B7/B8 and GNS1
      detect, besides this cytoplasmic cyclin B1 population, a moderate but clear
      nuclear concentration of the protein in cells that have not yet entered S phase.
      As for confluent populations of untransformed and tumour cells, they become
      enriched in G1- and G2-arrested cells that characteristically display a discrete
      nuclear or an intense cytoplasmic GNS1 immunostaining respectively. Altogether,
      our immunofluorescence data conjugated with the results of a detailed biochemical
      analysis suggest that human cyclin B1 would exist in situ as two distinguishable
      molecular entities differentially susceptible to in vitro degradation and
      exhibiting different timing, kinetics and site of accumulation during the cell
      cycle: one form (recognized by the polyclonal and GNS1 antibodies but apparently
      not by GNS 11) starts to build up inside the nucleus prior to entry in S phase
      and the other (in which both the GNS11 and GNS1 epitopes are readily accessible)
      emerges and accumulates in the cytoplasm beyond the G1/S boundary.

PMID- 8875984
TI  - A novel target for the Wilms' tumour suppressor protein (WT1) is bound by a
      unique combination of zinc fingers.
AB  - All isoforms of the Wilms' tumour suppressor protein, WT1, contain four
      consecutive zinc fingers which facilitate DNA binding. The predominant WT1
      transcript contains a 9 base pair insertion resulting in an additional three
      amino acids, lysine-threonine-serine (KTS), between zinc fingers 3 and 4. WT1
      zinc fingers 2, 3 and 4 are highly homologous to the zinc fingers of the early
      growth response gene, EGR1. However, only WT1--KTS is capable of binding an EGR1
      consensus site. In contrast, the previously described genomic fragment, +P5
      (D1S3309E), is bound by both WT1--KTS and WT1 + KTS. In this study, the region
      within + P5 to which both WT1 -- KTS and WT1 + KTS bind was defined as 5'
      GGAGAGGGAGGATC-3'. EGR1 did not bind + P5. By creating zinc finger deletions, we
      demonstrate that zinc finger 1, but not zinc finger 4, is critical for + P5
      binding; whereas zinc finger 4, but not 1, is necessary for the binding of WT1
      target sites within EGR1, PDGF A chain and IGF2 promoters. Thus, zinc finger
      usage can vary with target and + P5 may represent a novel type of WT1 binding
      site, the physiological relevance of which must be investigated.

PMID- 8875985
TI  - Early occurrence of metastatic differentiated thyroid carcinomas in transgenic
      mice expressing the A2a adenosine receptor gene and the human papillomavirus type
      16 E7 oncogene.
AB  - We report here the characterization of a transgenic mouse model (Tg-A2aR/Tg-E7)
      resulting from the coexpression of two oncogenic transgenes in the thyroid. The
      two transgenes (Tg-A2aR and Tg-E7) were placed under control of the thyroid
      specific thyroglobulin gene promoter, and directed the expression of either the
      A2a adenosine receptor that constitutively activates the cAMP pathway, or the E7
      protein of the human papillomavirus type 16, that binds and inactivates the
      retinoblastoma susceptibility gene product (Rb1). Transgenic mice expressing both
      transgenes were generated by interbreeding the Tg-A2aR and Tg-E7 transgenic
      lines, generated and characterized previously (Ledent et al., 1992, 1995). These
      mice develop a larger goiter than that of the two parental lines, and a severe
      hyperthyroidism comparable to that observed in the Tg-A2aR parental line. The
      main feature of the Tg-A2aR/Tg-E7 mice is the rapid occurrence of malignant
      lesions, and the dissemination of malignant thyroid tissue through the blood
      stream, generating multiple differentiated and functional metastases in the lung.
      These metastases appeared as early as 2 months after birth and their frequency
      increased to 75% over 3 months. They were associated with the presence of large
      vascular lakes in the thyroid. Electron microscopy of the malignant cells
      revealed nuclear features similar to those of human thyroid papillary carcinoma.
      These mice, in which two oncogenes are co-expressed in the thyroid, represent the
      first genetic animal model developing metastatic differentiated carcinomas of the
      thyroid with a high frequency.

PMID- 8875986
TI  - BRCA1 germline mutational spectrum in Italian families from Tuscany: a high
      frequency of novel mutations.
AB  - BRCA1 germline mutations confer susceptibility to familial breast and ovarian
      cancer. Mutational hot spots have never been detected in BRCA1 cDNA. Some
      mutations have been reported several times whereas some others appear to be
      population-related. In this study a group of 36 Italian families were analysed
      for BRCA1 germline mutations. All of them were screened by allele-specific
      oligonucleotide hybridization (ASO) for three recurrent mutations (185delAG,
      5382insC, nt332-T>G). Twenty families, selected because of their high risk of
      carrying BRCA1 mutations, were subjected to analysis of the entire coding
      sequence of the gene. A total of eight mutations were found. ASO screening
      demonstrated only one known mutation in one patient, whereas cycle sequencing
      revealed five new mutations. Three of these new mutations were frameshifts: one
      occurred in exon 11 (1499insA), one in exon 16 (4873delCA) and one in the splice
      site of exon 3 (252delAAgt). Two were missense mutations (Cys64Arg; Asn158Tyr).
      The same frameshift mutation, 1499insA, was detected in three unrelated families.
      Haplotype analysis supported the hypothesis that two of these families may have
      had common ancestors, whereas in the third family the analysis was uninformative.
      BRCA1 germline mutations were found in one out of two families with ovarian
      cancer, in five out of eight families with breast-ovarian cancer, and in two out
      of 11 families with breast cancer. All three families with 1499insA mutations
      included at least one case of ovarian cancer. The majority of the ovarian cancers
      (4/5) associated with detectable BRCA1 germline mutations were of serous
      histotype.

PMID- 8875987
TI  - Suppression of apoptosis by Bcl-2 or Bcl-xL promotes susceptibility to
      mutagenesis.
AB  - Bcl-2 appears to contribute to neoplasia primarily by promoting cell survival,
      rather than by stimulating cellular proliferation. Bcl-2, and the related protein
      Bcl-xL, each suppress apoptosis induced by a wide variety of stimuli in many
      different cell types. Here we report that suppression of apoptosis by Bcl-2 or
      Bcl-xL markedly elevates the levels of radiation-induced mutations. This enhanced
      mutagenesis is the result of an increase in mutation frequency (mutations per
      survivor) together with a moderate increase in viability. Ectopic expression of
      either Bcl-2 or Bcl-xL enhances radiation mutagenesis in cells with wtp53.
      Surprisingly, we found that ectopic expression of Bcl-xL also promotes
      mutagenesis in p53- cells. These results support the hypothesis that apoptosis
      plays a crucial role in maintaining genomic integrity by selectively eliminating
      highly mutated cells from the population.

PMID- 8875988
TI  - p120-v-Abl expression overcomes TGF-beta1 negative regulation of c-myc
      transcription but not cell growth.
AB  - Transformation of interleukin-3 dependent (IL-3) 32D-123 myeloid cells by p120-v
      Abl produced the factor-independent 32D-abl cell line. In 32D-abl cells, myc
      expression was found to be significantly higher than in the parental cells and
      was correlated with increased E2F-1 protein expression and DNA binding ability.
      Surprisingly, in 32D-abl cells, TGF-beta1, a potent G1/S inhibitor of 32D-123 and
      32D-abl cell growth, increased E2F transactivation as shown by increased c-myc
      promoter-CAT and GAL4-E2F-1 activity. In addition, TGF-beta1 was also found to
      increase E2F-1 protein levels but had no effect on steady-state retinoblastoma
      (RB) protein levels or phosphorylation state. In the absence of TGF-beta1,
      transient expression of RB in v-Abl expressing cells resulted in decreased c-myc
      transcription, inhibition of GAL4-E2F-1 driven transactivation and inhibition of
      cellular proliferation. RB and v-Abl were found to physically associate in vivo
      and in vitro via v-Abl's ATP binding region. In summary, these studies
      established that in myeloid cells: (1) v-Abl binds RB resulting in increased E2F
      1-driven c-myc transcription, and (2) an alternative pathway exists for TGF-beta1
      mediated growth inhibition of v-Abl-transformed cells, in which increased rather
      than decreased E2F-mediated c-myc transcription is observed.

PMID- 8875989
TI  - Bcl-2 has a cell cycle inhibitory function separable from its enhancement of cell
      survival.
AB  - Myeloid maturation appears to require exit from the cell cycle and leads to
      activation of apoptosis in the differentiated cells. The level of Bcl-2, which is
      known to promote cell survival, is shown here to influence both these critical
      steps. Bcl-2 function during myelomonocytic differentiation was investigated by
      introducing a deregulated bcl-2 gene into HL60 promyelocytic leukemia cells,
      which can be induced to exit the cell cycle and differentiate into granulocytes
      or monocytes. Deregulated Bcl-2 expression did not itself promote differentiation
      but extended the lifespan of mature cells elicited by granulocytic or monocytic
      inducers. Unexpectedly, in response to induction, Bcl-2 overexpression markedly
      potentiated and hastened cell cycle withdrawal into G(0). Enhanced survival
      cannot account for the elevated numbers of G(0) cells, because they arose under
      induction conditions that did not kill control cells. Since the cell cycle status
      and growth of uninduced cells was not affected by Bcl-2-overexpression, its cell
      cycle inhibitory activity must require an induction signal. While cell cycle
      withdrawal may be necessary for maturation, it was not sufficient, implicating a
      requirement for specific differentiative signals. These results identify, for the
      first time, a function for the bcl-2 proto-oncogene that is separable from its
      enhancement of cell survival.

PMID- 8875990
TI  - The amplicons in HL60 cells contain novel cellular sequences linked to MYC locus
      DNA.
AB  - We have previously determined that the amplified DNA present in the HL60
      promyelocytic leukaemia cell line contained 70 kb of continuous DNA sequences
      around the c-myc gene. In the work presented here we have further defined the
      HL60 amplicon and find it to be of the order of 160 kb and to contain a large
      region of DNA from chromosome 8q24 that is located at least 260 kb telomeric to
      the c-myc gene, joined to the 70 kb of DNA from the c-myc gene region. The novel
      chromosome 8 DNA coamplified sequences are not lost during multiple passage of
      HL60 cells since the composition of the chimeric amplicon is the same in both
      early passage HL60 cells containing only double minutes (DMs) and late passage
      isolates containing homogeneous staining regions (HSRs) at different chromosomal
      locations. This shows that the HL60 HSRs found in late passage cells are not
      generated anew but are directly derived from the precursor DMs. The HL60 cells
      contain two copies of chromosome 8, each with different polymorphic markers. Both
      these chromosome 8 homologues retain a c-myc gene as well as the region
      containing the coamplified DNA sequences indicating that the HL60 amplicons were
      not generated by simple DNA deletion. The constraint to maintain the novel DNA
      sequences coamplified with c-myc gene DNA suggests that these sequences may play
      some role in maintaining the growth potential and/or differentiation capacity of
      the HL60 cells.

PMID- 8875991
TI  - Phosphorylation-dependent targeting of c-Jun ubiquitination by Jun N-kinase.
AB  - Ubiquitination of key cellular regulatory proteins marks them for efficient
      degradation via the proteasome pathway. The delta domain of c-jun is essential
      for its ubiquitination and also for the activating phosphorylation of neighboring
      serines by the stress activated jun-N-terminal kinases (JNK). Using an in vitro
      model system we demonstrate that JNK is among the hydrophobic binding proteins
      that target c-jun for efficient ubiquitination. Immunodepletion of JNK markedly
      inhibits c-jun ubiquitination. Conversely, c-jun ubiquitination is increased by
      adding purified JNK2 or extracts prepared from cells transfected with JNK2.
      Although c-jun ubiquitination is enhanced by JNK, the phosphorylation of c-jun on
      Ser73 by JNK protects c-jun from ubiquitination and prolongs its half-life. The
      dual activity of JNK in targeting c-jun for ubiquitination or in protecting c-jun
      from entering this pathway via phosphorylation points to the role of JNK in the
      control of c-jun stability in cells exposed to environmental stress or
      inflammatory cytokines.

PMID- 8875992
TI  - Murine Wnt10a and Wnt10b: cloning and expression in developing limbs, face and
      skin of embryos and in adults.
AB  - Wnt genes encode a family of secreted proteins having oncogenic potential and
      important roles in developmental processes. We report the isolation of cDNAs for
      a novel murine Wnt gene, Wnt10a, and for two alternatively spliced transcripts of
      Wnt10b, as well as analyses of the expression patterns of these genes in adult
      and embryonic tissues. Wnt10a and full length Wnt10b encode relatively closely
      related (62% identity) Wnt proteins containing the 24 cysteines characteristic of
      most Wnt proteins. The deduced protein encoded by the alternatively spliced
      Wnt10b transcript lacks a central region encompassing 25% of the full length
      isoform. Both Wnt genes were widely expressed in the adult, although the levels
      of expression varied significantly. Wnt10a RNA was most abundant in adult brain
      with a high concentration in the pituitary gland, and expression of Wnt10b was
      highest in adult lung and uterus. RNAs of both genes were detected in thymus and
      spleen, tissues not previously reported as sites for Wnt gene expression. Wnt10a
      and Wnt10b expression broadly peaked at approximately 13.5 and 15.5 days of
      gestation, respectively, and Northern blot analyses of RNAs from dissected
      embryos revealed that expression of both genes was strongest in the face, limbs
      and skin and that Wnt10a was also expressed in the liver, the major site of
      hematopoiesis in the embryo. These expression patterns suggest that Wnt10a and
      Wnt10b may function in various tissues of the adult and embryo with notable
      expression in tissues responsible for the formation and maturation of blood
      cells, in the pituitary gland (Wnt10a), and in the face, limbs and skin of
      developing embryos.

PMID- 8875993
TI  - The serine protease inhibitors TLCK and TPCK inhibit the in vitro immortalization
      of primary human keratinocytes by HPV-18 DNA.
AB  - The human papillomaviruses (HPV) which are commonly found in anogenital
      malignancies express a viral E7 oncoprotein which possesses both immortalizing
      and transforming activities. The E7 protein forms a complex with the cellular
      tumor suppressor protein Rb and alters its interaction with transcription factor
      E2F, presumably interfering with cell cycle control and contributing to cellular
      transformation/immortalization. We demonstrated earlier that the serine protease
      inhibitors tosyl-L-phenylalanine chloromethyl ketone (TPCK) and tosyl-L-lysine
      chloromethyl ketone (TLCK) modified the HPV type 18 E7 protein in cell extracts
      as well as in living cells and abrogated its ability to form a complex with Rb.
      In the present study we evaluated the effect of TLCK or TPCK treatment on the
      immortalization of primary keratinocytes by transfected HPV-18 DNA. Supplementing
      the medium of primary foreskin keratinocytes with TLCK or TPCK during their
      immortalization with HPV 18 DNA demonstrated that either TLCK (5--10 microM) or
      TPCK (0.25 microM) could inhibit cellular immortalization by 50-100% without
      altering keratinocyte proliferation, suggesting that the topical application of
      these reagents in vivo could significantly interfere with HPV-mediated cellular
      transformation.

PMID- 8875994
TI  - High prevalence of a 30-base pair deletion and single-base mutations within the
      carboxy terminal end of the LMP-1 oncogene of Epstein-Barr virus in the Japanese
      population.
AB  - The presence of 30-base pair (bp) deletion mutants within the carboxy terminal
      end of the LMP-1 oncogene (BNLF-1 gene) of Epstein-Barr virus (EBV) has been
      reported in EBV-associated neoplasms. We analysed the 30-bp deletion and the
      single-base mutations of the LMP-1 gene in 13 spontaneously established
      lymphoblastoid cell lines (LCLs) from peripheral blood mononuclear cells of three
      healthy children, four patients with EBV-unrelated acute febrile illnesses, three
      patients with infectious mononucleosis (IM), and three patients with chronic
      active EBV infection (CEBV), and six frozen samples from four patients with CEBV
      and two patients with EBV-associated hemophagocytic syndrome (EBV-AHS). For
      molecular analysis of the carboxy terminal end of the LMP-1 gene, PCR was
      performed using primers spanning the carboxy terminal region of the LMP-1 gene.
      Direct sequence analysis of the PCR products revealed identical 30-bp deletion in
      14 of 19 samples (74%). Six point mutations at nucleotide positions 168357,
      168355, 168320, 168308, 168295, and 168225 were frequently identified regardless
      of disease status. Our findings revealed the carboxy terminal end of the LMP-1
      gene was mutational hot spots. The 30-bp deletion mutant is widely spread in the
      Japanese population and is not implicated in EBV-associated lymphoproliferative
      diseases.

PMID- 8875995
TI  - Human neural tissues express a truncated Ror1 receptor tyrosine kinase, lacking
      both extracellular and transmembrane domains.
AB  - Human heart, lung and kidney express a 6 kb mRNA encoding Ror1, a member of the
      receptor tyrosine kinase (RTK) family with as yet unknown ligand specificity. We
      used a Ror1 cDNA probe to screen a cDNA library prepared from the human
      neuronogenic teratocarcinoma line, NTera2, and cloned a 2373 nucleotide
      transcript. This transcript contains an open reading frame that encodes a 388
      amino acid protein identical with the cytosolic, C-terminal region of ror1 but
      lacking the ror1 transmembrane and entire extracellular domains. Northern blots
      demonstrate that mRNA encoding this truncated Ror1 ('t-Rorl') is abundantly
      expressed in fetal and adult human CNS, in human leukemia, lymphoma cell lines,
      and in a variety of human cancers derived from neuroectoderm. While previous
      studies have documented alternative splicing patterns within 5' and 3' regions of
      mRNAs encoding various RTKs altering their ligand binding specificity or their
      intracellular signaling, the present report is the first to demonstrate tissue
      specific alternative mRNA splicing causing loss of the entire extracellular and
      transmembrane regions of an RTK.

PMID- 8875996
TI  - Physical mapping of the DDX1 gene to 340 kb 5' of MYCN.
AB  - One of the most important prognostic factors in neuroblastoma is amplification of
      the MYCN gene, which is strongly associated with advanced stages of disease and a
      poor prognosis. Although the MYCN amplicon sometimes spans more than 1 Mb, no
      other consistently expressed sequences from the MYCN amplicon have been reported.
      However, DDX1, a gene encoding a DEAD box protein, was recently mapped to
      chromosome 2p24 and is frequently co-amplified with MYCN. Therefore, we performed
      genomic mapping with YACs to determine the physical relationship between DDX1 and
      MYCN, and whether DDX1 was contained within the core region of amplification.
      Based on YAC restriction mapping and content analysis, DDX1 maps 340 kb 5' of
      MYCN, outside the core domain of consistent amplification. Interestingly, we also
      determined by sequence analysis and detailed restriction mapping that G21,
      previously isolated as a 'neuroblastoma-specific' cDNA clone from an MYCN
      amplicon, is a partial cDNA of DDX1. Our data confirm that DDX1 is amplified in
      some but not all MYCN-amplified tumors, and that it is rearranged in other cases.
      This suggests that the co-amplification of DDX1 is due to its proximity to MYCN.

PMID- 8875997
TI  - Cloning and characterization of PTP-K1, a novel nonreceptor protein tyrosine
      phosphatase highly expressed in bone marrow.
AB  - A novel nonreceptor protein tyrosine phosphatase (PTP), PTP-K1, was identified
      using a consensus polymerase chain reaction-based approach. The full length cDNA
      encompasses an open reading frame of 1362 base pairs, predicting a protein of 453
      amino acid residues with a molecular mass of 54 kDa. The PTP domain is located in
      the N-terminal portion of the molecule and shares approximately 50% amino acid
      identify with two other nonreceptor PTPs: PEP and PTP-PEST. PTP-K1 is
      preferentially expressed in mouse bone marrow with transcripts of 1.7 kb, 1.9 kb
      and 3.5 kb. The 1.7 kb transcript was also detected in kidney, lung and ovary.
      The PTP domain of PTP-K1 was expressed as a fusion protein in bacteria and had
      intrinsic PTP catalytic activity. Indirect immunofluorescence microscopy in COS-7
      cells showed that PTP-K1 was localized to the cytoplasm. Ptp-k1 was mapped to
      mouse chromosome 1, and was closely linked to the interleukin-1 receptor gene.
      The high level expression of PTP-K1 mRNA in bone marrow suggests that PTP-K1 may
      be involved in signal transduction in growth and differentiation of hematopoietic
      cells.

PMID- 8875998
TI  - Primary structure, expression and chromosomal locus of a human homolog of rat
      ERK3.
AB  - We report the cloning and characterization of a human cDNA encoding a novel
      homolog of rat extracellular signal-regulated kinase 3 (ERK3). The cDNA encodes a
      predicted protein of 721 amino acids which shares 92% amino acid identity with
      rat ERK3 over their shared length. Interestingly, the human protein contains a
      unique extension of 178 amino acids at its carboxy terminal extremity. The human
      ERK3 protein also displays various degrees of homology to other members of the
      MAP kinases family, but does not contain the typical TXY regulatory motif between
      subdomains VII and VIII. Northern blot analysis revealed that ERK3 mRNA is widely
      distributed in human tissues, with the highest expression detected in skeletal
      muscle. The human ERK3 gene was mapped by fluorescence in situ hybridization to
      chromosome 15q21, a region associated with chromosomal abnormalities in acute
      nonlymphoblastic leukemias. This information should prove valuable in designing
      studies to define the cellular function of the ERK3 protein kinase.

PMID- 8875999
TI  - Clinical rehabilitation of the amputee: a retrospective study.
AB  - The aim of this study was to determine the rehabilitation outcome of lower limb
      amputee patients after clinical rehabilitation. Altogether 183 amputee patients
      admitted for clinical rehabilitation in the years 1987-1991 were reviewed by
      retrospective analysis of medical record data. Three groups of amputee patients
      were identified by reason for amputation. The vascular group: (N = 132), mean age
      67 years, mean admission time 119 days, 85% prosthetic fitting. The oncology
      group (N = 15), mean age 55 years, mean admission time 77 days, 60% prosthetic
      fitting. The traumatic amputee group: (N = 14), mean age 41 years, mean stay 134
      days and 100% prosthetic fitting. Some 22 patients were bilateral amputees and
      were assessed separately. The most important reasons for not fitting a prosthesis
      were oncological metastases, stump and wound healing problems. After
      rehabilitation 86% of all patients could be discharged home. These results are
      more favourable than those seen in previous studies.

PMID- 8876000
TI  - Functional outcome of lower-limb amputees: a prospective descriptive study in a
      general hospital.
AB  - This paper describes functional outcome of a population of lower limb amputees
      five months after amputation compared with their preoperative functional
      abilities and studies the relationship between potential determinants and
      functional outcome. Twenty out of 26 patients who underwent a lower limb
      amputation between December 1993 and August 1994 in a general hospital in
      Amsterdam were included in the study. Their functional abilities before
      amputation were retrospectively assessed using an ICIDH (International
      Classification of Impairments, Disabilities and Handicaps)-based questionnaire.
      Functional outcome was assessed after amputation of the lower limb using ICIDH
      based and SIP (Sickness Impact Profile)-questionnaires. The mean SIP scores were
      high (referring to a low functional outcome). Disabilities were spread over the
      five disability fields of the ICIDH. The functional outcome of the diabetic
      versus the non-diabetic group was lower on the physical, activities of daily
      living (ADL), psychological and communicative categories of the ICIDH. In most
      patients, functional outcome decreased. The diabetic patients compared to the non
      diabetics showed more diversity in functional outcome, compared with their
      preoperative functional abilities. Increasing age is significantly associated
      with a low functional outcome on the SIP scores. Diabetes is age-related for this
      sample. Co-morbidity and motivation are strongly age-related for this sample. It
      was concluded that lower-limb amputees appear quite disabled in all disability
      categories of the ICIDH and as assessed by the SIP scores. In most patients,
      functional abilities decrease after lower limb amputation. Age seems to be a
      significant factor related to functional outcome.

PMID- 8876001
TI  - Statistical analysis of amputations and trends in Korea.
AB  - Epidemiological research on amputees is being continued extensively world wide,
      but there are different epidemiologic reports from country to country. This study
      undertakes an epidemiologic report of the medical records of amputees in Korea
      which has developed very rapidly, when compared with other countries. This study
      included 4258 amputees who either had an amputation and/or received prosthetic
      training at Yonsei University College of Medicine, Severance Hospital from
      January 1970 to June 1994. The most common cause of amputation was trauma
      (66.7%), and the second most common cause was peripheral vascular disease. While
      amputations due to infection or trauma were the most common in the 1950's,
      amputations due to peripheral vascular disease have gradually increased until
      they now make up 23.5% of all amputations in the 1990's. Lower limb amputation,
      more common than upper limb amputation, accounted for 68.7% of all amputation.
      Multiple amputation accounted for 9.3% of all amputations, and the occurrence
      rate of multiple amputation was relatively higher in cases of burn injuries,
      train accidents, frostbite, and Buerger's disease than in cases brought about by
      other causes. The various amputation causes change according to the circumstances
      of the times, as can be seen in this study.

PMID- 8876002
TI  - Stump length as related to atrophy and strength of the thigh muscles in trans
      tibial amputees.
AB  - Stump length and the thigh muscles strength of the amputated limb are among the
      major factors influencing outcome of prosthetic rehabilitation of trans-tibial
      amputees. In the present study the authors evaluated and compared the strength of
      quadriceps and hamstrings muscles of both limbs in trans-tibial amputees, as
      measured by means of an electrical dynamometer. The obtained results showed that
      the thigh muscles of the sound limbs are significantly stronger than those of the
      amputated limbs (p < 0.01). The results obtained for amputees with shorter stumps
      were compared with those with longer stumps. In the group of amputees (n = 9)
      with a stump shorter than 15.1 cm, values of peak torque (in isokinetic
      contraction) and maximal average torque (in isometric contraction) were
      significantly (p < 0.5) weaker when compared to those (n = 9) with a stump longer
      than 15.1 cm. The results obtained for amputees with a higher rate of thigh
      muscle atrophy were compared to those with lesser atrophy. In the group of
      amputees where muscle atrophy was accompanied by decrease in thigh girth of over
      5.9 cm, muscles strength did not significantly decrease (p < 0.5) as compared to
      amputees where thigh girth decrease was less than 5.9 cm. It is concluded that
      atrophy of the thigh muscles of trans-tibial amputees is accompanied with a
      significant decrease in strength. In amputees with a short stump, the short lever
      action provided by the stump interferes with the ability of the thigh muscles to
      control the prosthesis efficiently during daily activities such as standing and
      walking.

PMID- 8876003
TI  - Use of an instrumented treadmill for real-time gait symmetry evaluation and
      feedback in normal and trans-tibial amputee subjects.
AB  - The purpose of this research was to evaluate a newly developed system for
      assessing and providing feedback of gait symmetry information in real time to
      subjects walking on a motorised treadmill (the CCF Treadmill). The advantages of
      the system are that it allows the rapid collection and comparison of temporal and
      kinetic parameters of gait for multiple successive strides, at a constant known
      speed, without forcing subjects to target their footsteps. Gait asymmetries of
      six normal (mean age 42.7 years) and six unilateral transtibial amputee subjects
      (mean age 41.7, and average 6.0 years using a prosthesis) were quantified. The
      amputee group was the reevaluated after receiving five minutes of training with
      each of three different types of real-time visual feedback (RTVF). Asymmetries in
      the measured parameters before feedback were 4.6 times greater in the amputee
      population than in the normal group, and were consistent with the finding of
      previous authors. Significant decreases in gait asymmetry were demonstrated for
      all forms of feedback after amputees received feedback training. Results,
      however, indicated that gait asymmetries for different variables are not
      necessarily related, and that more work needs to be done to identify those
      variables for which attaining a more symmetrical gait pattern is most beneficial.
      Further work also needs to be done to determine the long term effects of such
      RTVF training. The CCF Treadmill and RTVF were shown to be potentially useful
      tools both for defining rehabilitation targets and for quantifying patients'
      progress towards those goals.

PMID- 8876004
TI  - Outcome of fitting an ICEROSS prosthesis: views of trans-tibial amputees.
AB  - A report of the outcome of fitting ICEROSS prostheses to trans-tibial amputees
      from a subregional amputee rehabilitation centre is presented. This work has
      mainly concentrated on obtaining patients' own views to judge advantages and
      disadvantages of ICEROSS compared to their previous patellar-tendon-bearing (PTB)
      prostheses. Sixty-nine patients were entered for this study, but the results of
      the study are based on 54 patients who responded. Fifteen patients (27.7%) had
      rejected their ICEROSS prosthesis at the time of the study. Provision of ICEROSS
      prostheses did not improve indoor and outdoor walking abilities in terms of
      distance or use of other walking aids, nor were they more comfortable to wear. An
      increase in sweating in the first 3 months of wearing ICEROSS was significant,
      but settled afterwards. The amputees considered that the rate of stump skin
      breakdown with ICEROSS compared to their PTB prostheses was significantly less.
      Walking up and down stairs was more comfortable and in general overall rating of
      ICEROSS prostheses they were scored significantly higher by the amputees
      themselves. It is concluded that appropriate patient selection is vital and in
      certain cases ICEROSS will provide considerable benefits to the amputees.

PMID- 8876005
TI  - A comparison of energy expenditure by a high level trans-femoral amputee using
      the Intelligent Prosthesis and conventionally damped prosthetic limbs.
AB  - Comparisons were made between the Intelligent Prosthesis (IP), Mauch and
      pneumatic swing phase control damping systems on the same prosthesis worn by a
      high level trans-femoral amputee. Speeds self selected by corridor walking (4.4
      5.5 kmh-1) proved not to be sustainable for treadmill walking. Comfortable speeds
      were attained when the subject walked on a treadmill at 2.0, 2.6 and 3.2 kmh-1 in
      two tests for each prosthesis type. Oxygen uptake (VO2), cadence and heart rate
      were measured over 5 minute walks interspersed with rest periods. Spearman's
      correlation was used to test for differences between prosthesis types at each
      speed. At the two slower speeds no significant difference was found, but at the
      higher speed of 3.2 kmh-1, the IP was associated with a significantly lower VO2
      (p < 0.05). A two way analysis of variance with replication (ANOVA) demonstrated
      a significant difference between VO2 for different limb types (p = 0.015). A
      square law function was fitted to the mean VO2 for each prosthesis type by the
      method of least squares regression. ANOVA demonstrated a significant difference
      between velocity coefficients for the different prosthesis types (p < 0.05).
      Cadence was almost constant during the period of each walk, varying by 1 step min
      1 at most. However the test-retest differences in cadence were considerable. It
      is concluded that there was little difference in energy expenditure between
      prosthesis types at slower speeds, but at higher speeds (==> 3.2km h-1) the IP
      gave a lower oxygen uptake by about 10%.

PMID- 8876006
TI  - The potential for ambulation by severely handicapped cerebral palsy patients.
AB  - Whereas walking for paraplegic patients is now a routine clinical option,
      ambulation for heavily handicapped cerebral palsy patients is less well
      established. There are good reasons for supposing that therapeutic benefits
      similar to that achieved with paraplegic patients are possible for this group.
      However, the biomechanical problems which must be overcome are different and in
      many ways more difficult to address. The most important factors are identified as
      appropriate truncal support, control of abduction/adduction, rotation and flexion
      range at the hip, and of knee flexion. A means of applying these controls is
      described as being a combination of a walking frame and orthosis. The special
      walking frame provides adjustable support at thoracic, abdominal and sacral
      levels and incorporates castor steering and upper limb support. Controls on lower
      limb movements are applied through a special orthosis which has a readily
      available variation of specification to accommodate the wide range of conditions
      met in cerebral palsy. Practical application of a prototype system has shown that
      it can enable patients to walk unaided. However, in most cases it was used
      indoors only. Evaluation of the experience in applying the system has enabled the
      fundamental principles to permit more practical applications to be defined.

PMID- 8876007
TI  - Stiffness control in posterior-type plastic ankle-foot orthoses: effect of ankle
      trimline. Part 1: A device for measuring ankle moment.
AB  - A device was developed to measure the dorsi- and plantar flexion moment of
      plastic ankle-foot orthoses when deflected. It is operated by manually
      controlling a lever which is used to apply a nearly static force. Various
      orthoses can be classified according to the characteristics of the correcting
      force measured by this device. Simplicity and high reproducibility are the major
      advantages. However, to obtain measurements approximating the characteristics of
      orthoses under wearing conditions its use is restricted to orthoses made of low
      viscosity materials.

PMID- 8876008
TI  - Stiffness control in posterior-type plastic ankle-foot orthoses: effect of ankle
      trimline. Part 2: Orthosis characteristics and orthosis/patient matching.
AB  - The hingeless plastic ankle-foot orthosis (AFO) changes stiffness largely
      depending on how much plastic is trimmed around the ankle. To support proper
      selection of the orthosis and final adjustment of the orthotic stiffness, the
      correlation between the posterior upright width and the resistance to dorsi- and
      plantar flexion movements was measured in 30 posterior-type plastic AFOs. The
      posterior upright width was varied by regularly trimming around the ankle in nine
      stages. The resistance to dorsi- and plantar flexion movements was measured by
      bending the plastic AFOs 15 degrees with the measuring device described in Part
      1. All the plastic AFOs decreased in their resistance to both movements in
      proportion to the reduction of the posterior upright width. The maximum
      resistance to plantar flexion movement was about 28 Nm, which was strong enough
      to assist dorsiflexion in patients with severe spasticity. On the other hand, the
      maximum resistance to dorsiflexion movement measured was about 10 Nm, which was
      insufficient to stabilise the ankle in patients who lacked in plantar flexion
      strength. These findings suggested that this type of plastic AFO should be
      prescribed for patients who predominantly require dorsiflexion assist, and that
      the orthotic stiffness could be finally adjusted by trimming to exactly meet
      individual requirements.

PMID- 8876009
TI  - A CAD CAM digitizing adapter for spinal casts.
AB  - An adapter was designed to hold a negative cast of a torso in position for
      mechanical digitization. Once a spinal shape is digitized, the data file can be
      loaded into a CAD CAM system for modification and manufacturing of a positive
      model for an orthosis. The adapter currently fits a Seattle Digitizer (M+IND,
      Seattle, WA); however, the interface unit can be changed to accommodate other
      commercial digitizers. By using this adapter, current lower limb prosthetic CAD
      CAM systems can be used to design and manufacture spinal orthoses.

PMID- 8876010
TI  - Single photon emission computed tomography with iodoamphetamine-123 and
      neuropsychological studies in long-term abstinent alcoholics.
AB  - Ten long-term abstinent alcoholics (mean abstinence = 7.7 years) were compared
      with 13 recently detoxified substance-dependent inpatients (mean abstinence = 25
      days) and 8 nonalcoholic control subjects on global end regional measures of
      cortical cerebral blood flow (CBF), and on neuropsychological measures. CBF was
      assessed using 123iodoamphetamine (IMP) single photon emission computed
      tomography (SPECT) under conditions of behavioral challenge (Raven's Progressive
      Matrices). CBF and neuropsychological test performance were worse in the recently
      detoxified inpatients. Of greater interest, there was a dissociation in the long
      term abstinent group, which, while neuropsychologically indistinguishable from
      controls, showed significantly decreased mean cortical IMP uptake. We conclude
      that there may be persistent physiologic abnormalities in long-term abstinent
      alcoholics who have achieved full behavioral recovery. Smoking on the day of
      SPECT scanning was also identified to be a significant confound to understanding
      CBF changes in alcoholism.

PMID- 8876011
TI  - Multilead quantitative EEG profile of clozapine in resting and vigilance
      controlled conditions.
AB  - Clozapine is the prototype of a new class of drugs, referred to as 'atypical
      antipsychotics'. As a matter of fact, the antipsychotic activity of the drug was
      not predicted by the first studies with quantitative electroencephalography
      (QEEG), which actually reported an antidepressant pattern. All previous QEEG
      studies carried out in healthy subjects used a maximum of four leads, exploring
      only the posterior quadrants of the scalp. The present article reports findings
      of a multilead QEEG study carried out in 16 healthy men under resting and
      vigilance-controlled conditions. Increases in slow (delta, theta, and alpha1) and
      decreases in fast (alpha2 and beta) activities were found, corresponding to
      changes described for chlorpromazine-type antipsychotics. These results are
      compared with those of earlier studies. It is suggested that changes in the beta
      frequency range vary across subjects, whereas changes in slow and alpha activity
      are more consistent and critical for defining the QEEG profile of the drug.

PMID- 8876012
TI  - Increased prefrontal sulcal prominence in relatively young patients with unipolar
      major depression.
AB  - Although several studies have reported ventricular enlargement and sulcal
      prominence in mixed samples of patients with affective disorders (unipolar and
      bipolar subtypes), it is not established if these findings extend to a
      homogeneous sample of relatively young patients with unipolar major depression
      ventricular:brain ratio (VBR) and prefrontal sulcal prominence (PSP). In the
      present study, measures of ventricle-brain ratio (VBR) and prefrontal sulcal
      prominence (PSP) were compared in patients with affective disorders (n = 24, mean
      age = 39), medical control subjects (n = 40), patients with schizophrenia (n =
      101) on ventricular : brain ratio (VBR) and prefrontal sulcal prominence (PSP).
      No statistically significant differences were noted in VBR in the three groups.
      Both patient groups had significantly greater PSP than the medical control
      subjects but did not differ significantly from each other. The results of the
      present study extend the finding of prefrontal sulcal prominence, but not
      ventricular enlargement, to relatively young patients with unipolar depression.
      Furthermore, the results of the present study suggest that patients with
      schizophrenia and patients with affective disorders differ only slightly or not
      at all in brain morphology, at the level of resolution studied.

PMID- 8876013
TI  - Confirmation of reduced temporal limbic structure volume on magnetic resonance
      imaging in male patients with schizophrenia.
AB  - A structural deficit in the temporal lobes has been implicated in the
      pathogenesis of schizophrenia. A prospective magnetic resonance imaging (MRI)
      study was carried out in 20 young male patients with schizophrenia and 20 age
      matched healthy male volunteers. Volumetric measurements were performed in all
      slices with temporal lobe cross-sections from the temporal pole to the tip of the
      Sylvian fissure. Volumetric assessment included the temporal lobe as a whole,
      hippocampal formation and amygdala complex, temporal horn and cella media of the
      lateral ventricle, the third ventricle, and hemispheric volume in all slices that
      showed temporolimbic structures. Brain structural deficit in the patients was
      most conspicuous in the posterior portion of the hippocampal formation.
      Significant effects of diagnosis were also found for the total temporal lobe and
      the third ventricle. Multiple regression analysis revealed posterior hippocampal
      volume to be significantly determined by diagnosis, but not by age or by temporal
      lobe or hemispheric volume. Significant correlations of morphologic and clinical
      parameters were restricted to negative correlations of temporal lobe volume with
      the global rating and sum score of the Scale for the Assessment of Negative
      Symptoms. The study confirms subtle temporolimbic deficit reported in previous
      MRI studies in patients with schizophrenia.

PMID- 8876014
TI  - Landmark-based registration and measurement of magnetic resonance images: a
      reliability study.
AB  - We report a magnetic resonance imaging (MRI) study in a large number of subjects
      that examines various analytic techniques for anatomical landmark information.
      The initial issue involved interrater reliability in locating landmarks along the
      midsagittal plane. Another issue dealt with using landmarks to register (linear)
      individual scans for subsequent analyses or more sophisticated registration
      techniques. We next explore the use of interlandmark distances as indices of
      brain size. Twenty-seven landmarks were chosen from the midsagittal slice of 101
      abnormal subjects. Interrater reliability estimates on a subset of the scans were
      excellent overall. Rotating to anterior-posterior commissure points was the best
      of the tested two-point registrations, although an average angular rotation was
      better. Reliability and validity for landmark-derived measures of size were
      excellent. Landmark-based analyses offer opportunities to explore shape and size
      questions, although they are not appropriate for addressing all questions. Under
      specific conditions, landmark data can be generated quickly and accurately.

PMID- 8876015
TI  - Striatal dopamine D2 receptor quantification and superior temporal gyrus: volume
      determination in 14 chronic schizophrenic subjects.
AB  - Chronic schizophrenic (n = 14) and normal subjects (n = 15) were studied with
      resonance imaging (MRI) and positron emission tomography (PET). Two PET scans
      were carried out to estimate caudate dopamine D2 receptor densities. MRI was used
      to measure the volume of the superior temporal gyrus. Average striatal D2
      receptor density (Bmax) was significantly higher in the schizophrenic group than
      in the normal group. Average left superior temporal gyral volume was
      significantly smaller in the schizophrenic group than in the normal group, and
      the same tendency was found for the right superior temporal gyrus. Thus, the main
      finding of this combined analysis of functional and structural neuroimaging
      techniques was an inverse relationship between reduced superior temporal gyral
      volume and elevated striatal D2 receptor Bmax values. These preliminary findings
      require confirmation in larger groups of patients and control subjects.

PMID- 8876016
TI  - In schizophrenia, some dopamine D2-like receptors are still elevated.

PMID- 8876017
TI  - Contralateral turning elicited by unilateral stimulation of dopamine D2 and D1
      receptors in the nucleus accumbens of rats is due to stimulation of these
      receptors in the shell, but not the core, of this nucleus.
AB  - The goal of this study was to determine whether dopamine D2 and/or D1 receptors
      in the shell and the core of the nucleus accumbens of rats have a differential
      role in turning behaviour. Unilateral injection of a mixture of the dopamine D2
      receptor agonist quinpirole (10 micrograms) and the dopamine D1 receptor agonist
      1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7, 8-diol (SKF 38393, 5 micrograms)
      into the shell of the nucleus accumbens produced contralateral turning, when
      doses which per se were ineffective were injected. This effect was far greater
      than that found after similar injections into the core of the nucleus accumbens.
      The effect elicited from the shell was significantly attenuated by prior
      administration of either the dopamine D2 receptor antagonist l-sulpiride (25
      mg/0.5 microliters) or the dopamine D1 receptor antagonist (8-chloro-2,3,4,5
      tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH 23390, 0.5 micrograms/0.5
      microliters) into the same region. These data together with the fact that l
      sulpiride is known to be a valid tool to differentiate the involvement of
      distinct regions within the shell underlie the conclusion that dopamine D2 and D1
      receptors in the shell, but not the core, of the nucleus accumbens play a
      critical role in the contralateral turning induced by unilateral injection of
      dopamine receptor agonists into this nucleus. The results are discussed in view
      of the known output pathways of the shell.

PMID- 8876018
TI  - Evidence for dissociable mechanisms of amphetamine- and stress-induced behavioral
      sensitization: effects of MK-801 and haloperidol pretreatment.
AB  - The present study examined the ability of pretreatment with MK-801 or haloperidol
      to block the induction of behavioral sensitization to amphetamine challenge by
      repeated immobilization stress in male Sprague-Dawley rats. Fifteen minutes
      before each of ten 30-min restraint sessions, rats were administered saline, MK
      801 (0.01, 0.10 or 0.25 mg/kg i.p.) or haloperidol (0.10 or 0.25 mg/kg i.p.).
      Control rats received the same injection regimen without restraint. An additional
      experiment examined the ability of MK-801 to block the induction of sensitization
      by repeated d-amphetamine. In this experiment, rats were administered saline or
      MK-801 (0.25 mg/kg i.p.) 15 min before each of ten amphetamine injections (1.0
      mg/kg i.p., administered under the same regimen as immobilization stress). Four
      days after the final immobilization or amphetamine injection, rats were tested
      for locomotor response to novelty, saline and d-amphetamine (1.5 mg/kg i.p.).
      Exposure to repeated immobilization stress significantly enhanced the locomotor
      response to amphetamine challenge but not to saline challenge whether rats were
      pretreated with saline, MK-801 or haloperidol. Secondary analysis of dose effects
      in each pretreatment group revealed that at 0.25 mg/kg, repeated MK-801 in itself
      induced sensitization to the response to amphetamine in control rats and
      potentiated stress-induced sensitization in restrained rats. In contrast, the
      sensitization induced by repeated amphetamine was attenuated by MK-801
      pretreatment. Neither dose of haloperidol affected the locomotor response to
      saline or amphetamine in control or stressed rats. These results indicate that
      the effects of MK-801 on the induction of sensitization are complex and suggest
      that amphetamine- and stress-induced behavioral sensitization may arise through
      different mechanisms.

PMID- 8876019
TI  - Effects of the delta opioid against BW373U86 in pigeons trained to discriminate
      fentanyl, bremazocine and water in a three-choice drug discrimination procedure.
AB  - The delta opioid agonist BW373U86 was examined alone and in combination with mu
      agonists in pigeons trained to discriminate the mu agonist fentanyl (0.056
      mg/kg), the kappa agonist bremazocine (0.017 mg/kg), and distilled water in a
      three-choice drug discrimination procedure. BW373U86 (0.01-10 mg/kg) produced a
      dose-dependent increase in fentanyl-appropriate responding and complete
      generalization to fentanyl in four of five subjects. BW373U86 did not elicit
      bremazocine-appropriate responding in any of the subjects. Fentanyl-appropriate
      responding elicited by BW373U86 was antagonized by the delta selective antagonist
      naltrindole (0.1-10 mg/kg) but not by the mu selective antagonist naloxone (0.1
      30.0 mg/kg). When BW373U86 was administered in combination with the mu agonists
      fentanyl, morphine and nalbuphine, a low dose of BW373U86 (0.01 mg/kg) that
      elicited primarily water-appropriate responding when administered alone did not
      produce a significant change in the ED50 values for fentanyl, morphine or
      nalbuphine. Higher doses of BW373U86 (0.1-1.0 mg/kg) increased levels of fentanyl
      appropriate responding elicited by low doses of fentanyl, morphine and nalbuphine
      to levels similar to those produced by BW373U86 alone. These results indicate
      that BW373U86 shares discriminative stimulus properties with the mu agonist
      fentanyl in pigeons, possibly by acting at delta opioid receptors. However,
      BW373U86 does not potentiate the discriminative stimulus effects of mu agonists
      or share discriminative stimulus effects with the kappa agonist bremazocine.

PMID- 8876020
TI  - Effects of the selective angiotensin II receptor antagonists losartan and
      PD123177 in animal models of anxiety and memory.
AB  - There is increasing interest in the potential functional role of the octapeptide
      angiotensin II (AII) in psychiatric and cognitive disorders. The novel
      angiotensin II (AII) receptor antagonists, losartan and PD123177, selective for
      the AT1 and AT2 receptor subtypes respectively, constitute important
      pharmacological tools for the assessment of the behavioural consequences of
      modulation of AII function. The present series of studies investigated the
      effects of each compound in two animal models of anxiety, the rat elevated zero
      maze and mouse light/dark box, and two models of working memory in the rat, the
      operant delayed matching to position (DMTP) task and the spatial reinforced
      alternation test in the T-maze. Our data indicate that both compounds (0.01-10
      mg/kg s.c.) were without significant effect in any of the behavioural assays.
      Using the present methods and strains of laboratory rodents, these findings
      provide no support for the involvement of AII receptor function in the mediation
      of anxiety of working memory.

PMID- 8876021
TI  - Effect of sensitization of stereotypy on the acquisition and retention of
      tolerance to amphetamine hypophagia.
AB  - The purpose of this study was to determine whether prior sensitization of
      stereotypy interferes with the development and retention of tolerance to
      amphetamine-induced hypophagia. Rats were given intermittent injections of either
      amphetamine (2.5 mg/kg) to induce sensitization of stereotypy, or saline.
      Subgroups from each group then received daily injections of either amphetamine (2
      mg/kg) or saline and access to milk for 30 min. Both sensitized and nonsensitized
      groups became tolerant to drug-induced hypophagia at about the same rate and to
      about the same extent. Such tolerance was accompanied by a decrease in the
      frequency of stereotyped movements while milk was available. The rats were then
      given daily milk tests for 4 weeks without injections. Subsequent tests with
      amphetamine revealed that both groups lost tolerance to drug-induced hypophagia
      and displayed more intense stereotypy than they had prior to drug withdrawal. We
      conclude that sensitization of stereotypy produced by intermittent injections of
      amphetamine (2.5 mg/kg) does not retard the development of tolerance to drug
      induced hypophagia and does not alter the rat's ability to suppress stereotyped
      movements. However, the loss of tolerance following drug withdrawal may have been
      due to the development of more intense stereotypy and/or the "unlearning" of
      previously acquired strategies for suppressing stereotypy.

PMID- 8876022
TI  - Cigarette smoking and psychophysiological stress responsiveness: effects of
      recent smoking and temporary abstinence.
AB  - Studies comparing the cardiovascular function and stress responsiveness of
      regular smokers and non-smokers have produced mixed results, possibly because of
      variable intervals between stress tests and recency of smoking. This experiment
      compared the cardiovascular, cortisol and affective responses to a problem
      solving task of non-smoking young men (n = 16) and regular smokers randomised to
      overnight abstinence (n = 14) and smoking 30 min prior to testing (n = 19).
      Smoking status was validated biochemically. Overnight abstinence was associated
      with reduced diastolic blood pressure at rest and with enhanced diastolic
      pressure and emotional responses to the task compared with other conditions.
      Recent smokers showed elevated heart rates, suppressed cardiac baroreceptor
      reflex sensitivity and reduced cortisol responsiveness, but did not differ from
      non-smokers in blood pressure responses. The behavioral performance of the
      abstinent group was impaired, and their craving was greater than that of recent
      smokers. Both groups of smokers reported more dysphoric mood than non-smokers,
      and showed only limited recovery of emotional equilibrium following tests. The
      results are discussed in relation to mechanisms linking smoking, stress
      responsiveness and cardiovascular disease risk. The methodological implications
      for including regular smokers in psychophysiological studies are also considered.

PMID- 8876023
TI  - Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c
      receptor.
AB  - Interactions of the selective serotonin reuptake inhibitors (SSRIs) citalopram,
      fluoxetine and its main metabolite norfluoxetine, and the tricyclic
      antidepressant (TCA) imipramine with the rat serotonin 5-HT2C receptor in a
      clonal cell line and in the rat choroid plexus were investigated by radioligand
      binding and phosphoinositide (PI) hydrolysis assays. For comparison, the
      affinities of a variety of other antidepressants of different chemical classes
      for the cloned rat 5-HT2C and 5-HT2A receptors were also determined by
      radioligand binding assays. Fluoxetine displayed relatively high affinity for the
      5-HT2C receptor in the choroid plexus, with a Ki value for inhibition of
      [3H]mesulergine binding of 55.4 nM. The Ki values for imipramine, norfluoxetine
      and citalopram were 136 nM, 203 nM, and 298 nM, respectively. Similar rank order
      of potency was detected in PI hydrolysis assays, which showed that these drugs
      are antagonists at the 5-HT2C receptor without exhibiting inverse agonist
      activity. [3H]Ketanserin (5-HT2A) binding assays revealed that the SSRIs
      fluoxetine, norfluoxetine and citalopram show 10- to 23-fold selectivity for the
      5-HT2C receptor in vitro, whereas the TCA imipramine does not. Many other TCAs
      also had high to intermediate affinity for both 5-HT2A and 5-HT2C receptors. The
      present data provide evidence that fluoxetine, norfluoxetine and citalopram,
      along with many other antidepressant compounds, interact directly with the 5-HT2C
      receptor.

PMID- 8876024
TI  - Pharmacokinetics and bioavailability of midazolam after intravenous,
      subcutaneous, intraperitoneal and oral administration under a chronic food
      limited regimen: relating DRL performance to pharmacokinetics.
AB  - The effects of midazolam on animal behavior often are evaluated under a
      chronically food-limited regimen, which is used to implement food-reinforced
      performance, but the corresponding pharmacokinetics are lacking. The present
      study investigated the pharmacokinetics of midazolam after i.v., s.c., i.p., and
      p.o. administration in food-limited rates. A two-compartment model best described
      the concentration-time profiles for the four routes of administration. The rate
      of midazolam absorption was rapid, and peak concentrations were attained in less
      than 7 min for the three extravascular routes. The mean volume of distribution of
      the central compartment and clearance were 0.77 l/kg and 2.03 l/h per keg,
      respectively. Midazolam elimination half-lives for the four routes of
      administration ranged from 23.1 to 49.5 min, and metabolites could not be
      detected. The mean absolute bioavailability was route-dependent: 39.3% (s.c.)
      19.2% (i.p.) and 4.6% (p.o.). The markedly low oral bioavailability found in food
      limited rats contrasted to the value reported for free-feeding rates (45%).
      Although the i.p. route yielded the highest maximum concentration on occasion,
      serum midazolam concentration-time profiles were variable, but did correspond to
      respective sedative responses. DRL 45-s performance after s.c., i.p., and p.o.
      administration further supported the advisability of using the s.c. route of
      administration, as opposed to the i.p. route, for studying midazolam dose
      response relations. The bioavailability values assessed from DRL performance also
      agree with the measured pharmacokinetic values.

PMID- 8876025
TI  - AMPA antagonists differ from NMDA antagonists in their effects on operant DRL and
      delayed matching to position tasks.
AB  - The effects of NBQX (1.56-7.5 mg/kg, i.p.), a competitive antagonist at the AMPA
      type of glutamate receptor, were studied in two operant behavioural paradigms,
      differential reinforcement of low response rates (DRL), and delayed matching to
      position (DMTP), which have been shown to be sensitive to the antagonists of the
      NMDA type of glutamate receptor. Additionally, the non-competitive AMPA
      antagonist, GYKI 52466 (7.5-15 mg/kg, i.p.), was studied in the DRL procedure. As
      a positive control, the non-competitive NMDA antagonist, MK 801 (0.0125-0.1
      mg/kg, i.p.) was studied in both procedures. During performance of the DRL
      schedule, MK 801 increased response rates in a dose dependent manner, and
      decreased the number of reinforcers obtained. The increase in response rates
      could be attributed to both a shift in the median inter-response time (IRT) to
      shorter intervals, and to a marked, dose dependent increase in the occurrence of
      bursts of responses (responses occurring within 3 s of a previous response). In
      contrast, NBQX and GYKI 52466 both decreased response rates in a dose dependent
      fashion, and did not shift the distribution of the IRTs, or increase the
      occurrence of burst responding. In the DMTP procedure, accuracy of matching
      decreased with increasing delay (up to 30 s, between presentation of sample and
      opportunity to respond). NBQX disrupted responding at a dose of 7.5 mg/kg, but
      lower doses were ineffective in influencing accuracy of performance of the
      discrimination. In contrast, MK 801 (0.1 and 0.2 mg/kg) reduced accuracy of
      matching at all delays, while tending to increase the speed of responding. These
      data demonstrate differences in the effects of AMPA and NMDA antagonists on
      performance of well trained operant behaviour.

PMID- 8876026
TI  - Lorazepam impairs perceptual integration of visual forms: a central effect.
AB  - Previous studies have shown a lorazepam effect on visual perception. We tested
      whether this impairment resulted from a peripheral effect induced by
      benzodiazepines. A first experiment showed that a single dose of lorazepam
      induces an oculomotor imbalance without impairing visual acuity or accommodation.
      In a second experiment, we tested whether the impairment induced by lorazepam on
      visual perception still occurred in monocular vision. Subjects matched incomplete
      forms controlled on the spacing and alignment of their local contour elements. A
      reference object was first displayed and followed by two laterally displayed
      objects, a target and a distractor. The distractor was the mirror-reversed
      version of the target. Performance was impaired in the lorazepam group when the
      reference was an incomplete form with a spacing of 10.8' or 22.2' of arc. These
      results were not correlated with sedation. They confirm that lorazepam has a
      central deleterious effect on visual perception. A post-hoc analysis also
      suggested that lorazepam-treated subjects used asymmetry in the stimuli as a
      compensatory strategy. This result is discussed in relation to previous
      hypotheses about the physiological mechanisms that determine the effects of
      lorazepam on visual perception.

PMID- 8876027
TI  - Persisting changes in brain glucose uptake following neurotoxic doses of
      phencyclidine which mirror the acute effects of the drug.
AB  - Phencyclidine (PCP) can induce a model psychosis which has a number of
      similarities to dementias and schizophrenia. In some cases the psychosis persists
      for prolonged periods after drug discontinuation. N-Methyl-D-aspartate (NMDA)
      antagonists such as PCP induce increases in glucose metabolism in a variety of
      brain structures but most notably in limbic regions such as retrosplenial,
      piriform, and entorhinal cortex, hippocampus, and olfactory tubercle. When given
      continuously for several days, these NMDA antagonists induced neural degeneration
      in these same critical limbic areas. In the present study regional 2
      fluorodeoxyglucose (FDG) uptake was measured in rats at both 24 h and 10 days
      after neurotoxic, 5-day "binge" PCP administration. At 24 h after minipump
      removal there were persisting and large increases in glucose uptake in many brain
      regions, with maximal changes in the same limbic structures in which
      neurotoxicity has been observed. Surprisingly, many of these regions still showed
      elevated glucose metabolism after 10 days of recovery. These findings suggest an
      anatomical and neurochemical substrate for the persisting psychosis which can
      occur following PCP.

PMID- 8876028
TI  - Pharmacokinetic responses to caffeine in volunteers with higher scores for
      neuroticism.

PMID- 8876030
TI  - Design of novel cholecystokinin-B receptor ligands based on the 'double-ring
      system' approach.
AB  - A structurally novel series of cholecystokinin-B (CCK-B) receptor ligands has
      been designed and synthesized based on the 'double ring system' theory of
      receptor recognition. Compounds 2b-cis and 2g-cis from this 1-amino-2
      benzyltetralin series show modest CCK-B receptor affinity, with IC50 values of
      48.5 nM and 39.0 nM, respectively. The results are discussed in the context of
      ongoing efforts to identify the CCK-B receptor binding site for nonpeptide
      ligands.

PMID- 8876029
TI  - Novel CCK-B receptor agonists: diketopiperazine analogues derived for CCK4
      bioactive conformation.
AB  - Recently, we proposed a CCK-B agonist bioactive conformation characterized by an
      'S' shape of the peptidic backbone which was derived from structure-activity
      relationships and conformational analysis of CCK4 (Trp-Met-Asp-Phe-NH2)
      analogues. Using this template, we report here the synthesis of cyclic CCK4
      analogues which contain, in place of the Trp-Met dipeptide, a diketopiperazine
      moiety resulting from a cyclization between Nle and N-substituted (D)Trp residues
      and coupled with a small linker to Asp-Phe-NH2. Some of these compounds displayed
      good affinities and selectivities for the CCK-B receptor. The results are
      discussed in terms of size, hydrophobicity and spatial orientation of the side
      chains on the diketopiperazine ring. The most potent ligand exhibited potent and
      full CCK-B receptor agonist properties in promoting the hydrolysis of inositol
      phosphates (EC50 = 8 nM) in CHO cells, stably transfected with the rat brain CCK
      B receptor. This compound was also shown to be a potent selective CCK-B/gastrin
      receptor agonist since, it increased gastric acid secretion measured in
      anesthetized rats on i.v. administration. These compounds provide a rigid
      template for the design of non-peptide CCK-B agonists, by modification of the
      remaining peptide moiety.

PMID- 8876031
TI  - Characterization of novel peptoid agonists for the CCK-A receptor.
AB  - The successful design of peptoid CCK-B receptor antagonists using rational
      approaches suggested that it might be feasible to develop similar non-peptide
      small molecule agonists with potential therapeutic applications. We now report
      the characterization of such a compound with full agonist activity at CCK-A
      receptors on rat exocrine pancreatic acinar cells. The compound, PD149164,
      stimulated a similar maximal response to CCK8 from the exocrine pancreas in
      anaesthetized rats in vivo, and from isolated pancreatic acini in vitro it also
      generated intracellular Ca2+ oscillations similar to those evoked by CCK8. These
      effects were inhibited by the CCK-A antagonist L-364,718. Interestingly, the
      enantiomer of PD149164, PD151932, was a CCK-A antagonist and blocked PD149164
      stimulated effects on the exocrine pancreas. The data indicate that it is
      possible to develop both agonist and antagonist activities in enantiomers of
      small non-peptide molecules.

PMID- 8876032
TI  - The role of cholecystokinin in nociception, neuropathic pain and opiate
      tolerance.

PMID- 8876033
TI  - Are radioligand antagonist/agonist binding ratios in rat pancreas predictive of
      functional efficacy of cholecystokinin receptor agonists and antagonists?
AB  - Radioligand binding assays have been previously used to predict the relative
      efficacy of novel ligands. In the present study we have investigated whether for
      the cholecystokinin CCK-A receptors in the rat pancreas, the ratio of binding
      affinities for compounds for antagonist and agonist radioligands are predictive
      of functional activity. A number of classical cholecystokinin agonists, such as
      CCK-8S, caerulein, CCK-8DS, pentagastrin and CCK-4 had antagonist/agonist binding
      ratios of 4-fold or greater. All compounds behaved as full agonists in the
      stimulation of phosphatidylinositol (PI) turnover and increase in amylase
      secretion in rat pancreas. In contrast, compounds such as the benzodiazepine
      derivatives devazepide and L-365,260 had binding ratios of less than one and
      lacked agonist activity in either functional assay. Interestingly, the dipeptide
      derivative CI-988, which has been described as a selective CCK-B antagonist, was
      found to have an antagonist/agonist binding ratio of 1.5 for the CCK-A receptors
      in rat pancreas which was sufficiently high for this compound to behave as a full
      agonist in the amylase assay, although CI-988 did not exhibit agonist activity in
      the PI assay. These results suggest that the effective receptor reserve in the
      amylase assay is greater than that required to stimulate PI turnover, and that
      the selective peptoid CCK-B antagonist CI-988 has weak agonist activity at CCK-A
      receptors.

PMID- 8876034
TI  - The influence of guanyl nucleotide on agonist and antagonist affinity at guinea
      pig CCK-B/gastrin receptors: binding studies using [3H]PD140376.
AB  - The novel radioligand [3H]PD140376 was used to label receptors that bind
      cholecystokinin (CCK) and related peptides in membranes prepared from guinea-pig
      brain and gastric glands. Under control conditions, measurements of the apparent
      affinity of 11 agonist and 16 antagonist ligands in both tissues revealed a
      strong positive relationship between the affinity of a compound in either tissue
      (slope of the regression line = 0.89, r2 = 0.908). Agonists consistently showed
      higher affinity for sites in gastric glands compared to brain. If agonists were
      excluded from the analysis, the degree of correspondence between affinities
      measured in each tissue was almost perfect (slope = 0.93, r2 = 0.986). In the
      presence of the guanyl nucleotide 5'-guanylimidodiphosphate (GppNHp), agonist
      affinity in gastric glands, but not brain, was reduced such that there was a
      direct relationship between binding affinity in each tissue. These data are
      consistent with the notion that the receptor sites in brain and gastric glands,
      which recognise CCK and gastrin related compounds, are the same and of the CCK
      B/gastrin subtype. The receptors in the two respective tissues, however, do
      appear to differ in the degree of post-receptor coupling. These findings may
      explain previously reported differences between gastrin and CCK-B receptors that
      were based upon binding studies using agonist ligands.

PMID- 8876035
TI  - GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor,
      and potent broad-spectrum anti-emetic activity.
AB  - It has been demonstrated recently that antagonists of the tachykinin NK1
      receptor, specifically CP-99,994 and GR203040, possess anti-emetic activity in a
      range of species. To optimise this activity, a series of analogues based around
      the structure of GR203040 have been synthesised and their affinity at the human
      tachykinin NK1 receptor determined. In addition, the potency of these analogues
      to inhibit emesis induced in the ferret by whole-body X-irradiation has been
      examined. A range of substitution at the C-1 position of the tetrazole moiety in
      GR203040 were explored in vitro and in vivo. The trifluoromethyl compound,
      GR205171, was the most potent antagonist with regard to the ability to inhibit
      emesis induced by X-irradiation. This compound was demonstrated to have a broad
      spectrum of anti-emetic activity, inhibiting emesis in the ferret induced by
      cisplatin, cyclophosphamide, morphine, ipecacuanha and copper sulphate.
      Furthermore, emesis was also inhibited in the house-musk shrew, Suncus murinus,
      when induced by either motion or cisplatin, and in the dog when induced by
      ipecacuanha. GR205171 has the most potent anti-emetic activity of any tachykinin
      NK1 receptor antagonist described to date. The compound is orally active in the
      ferret and dog, long-lasting, and warrants further investigation as a potential
      broad-spectrum anti-emetic agent.

PMID- 8876036
TI  - A review of the design, synthesis and biological activity of the bicyclic
      hexapeptide tachykinin NK2 antagonist MEN 10627.
AB  - We review the reported data on the design, the conformational features and the
      pharmacological properties of the bicyclic peptide tachykinin NK2 receptor
      antagonist MEN 10,627 or cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta). MEN
      10,627 possesses a highly constrained structure characterized by two consecutive
      beta-turns, as confirmed by the almost coincident results of NMR and X-ray
      analyses. The compound has been efficiently synthesized by solid-phase
      methodology using either Boc or Fmoc strategies. It is quite stable to metabolic
      degradation and is endowed with high affinity and selectivity for NK2 receptor
      expressed in various species. At the hamster NK2 receptor MEN 10,627 is about 30
      fold more potent than the nonpeptide NK2 receptor antagonist, SR 48,968, while
      the converse is true for the rabbit NK2 receptor. MEN 10,627 and SR 48,968 show
      comparable affinities for the human NK2 receptor. MEN 10,627 produces a long
      lasting inhibition of the response to the selective NK2 receptor agonist [beta
      Ala8]NKA(4-10) in the rat urinary bladder in vivo after intravenous, intranasal
      and intraduodenal administration. Therefore different administration routes are
      possible for this compound that overcomes the usual drawbacks for the application
      of peptides as drugs.

PMID- 8876037
TI  - Structure-affinity studies of C-terminally modified analogs of neuropeptide Y led
      to a novel class of peptidic Y1 receptor antagonist.
AB  - A novel type of C-terminally modified analogs of the 36-mer peptide hormone
      neuropeptide Y has been synthesized, characterized and tested with respect to
      receptor affinity and biological activity in various systems. The compounds were
      obtained by synthesizing the fully protected peptide fragment NPY 1-35 or analogs
      of this, and coupling it in solution to various amines, alcohols, and modified
      tyrosine residues. It could be confirmed, that the C-terminal tyrosineamide of
      NPY is essential for its affinity to the Y1 receptor subtype. Obviously, the
      amino group of the amide part is more important than the oxygene atom of the
      carbonyl group, as NPY 1-35-tyrosinol has a lower affinity than NPY 1-35
      tyrosinethioamide. NPY 1-35-tyramide could be shown to act as an antagonist in a
      Ca2+ release assay in human neuroblastoma cells. Analogs of NPY 1-35-tyramide
      showed the same structure-affinity relationships as NPY itself, suggesting, that
      there exists the same binding mode for the agonist and the antagonist.

PMID- 8876038
TI  - BIBP 3226, the first selective neuropeptide Y1 receptor antagonist: a review of
      its pharmacological properties.
AB  - Based on the assumption that the pharmacophoric groups interacting with the Y1
      receptor are located in the C-terminal part of neuropeptide Y, low molecular
      weight compounds with high affinity and selectivity for the Y1 receptor were
      designed and synthesized. The prototype BIBP 3226 possesses affinity for the Y1
      receptor in the nanomolar range. In addition, this compound is selective
      displaying rather low affinity for Y2, Y3, Y4 and a set of 60 other receptors.
      Both biochemical and pharmacological studies showed that BIBP 3226 behaves as a
      competitive antagonist. Using BIBP 3226 it was possible to investigate the role
      of NPY and/or Y1 receptors in blood pressure regulation. The interesting
      observation was that antagonism to Y1 receptors had no major influence on the
      basal blood pressure but attenuated stress induced hypertension. This strongly
      supports the hypothesis that NPY is mainly released during stress involving
      intense sympathetic nervous system activation. Moreover, BIBP 3226 can be used to
      characterize NPY receptor subtypes. For instance, we were able to show that
      presynaptic NPY receptors mediating catecholamine release do not solely belong to
      the Y2 subtype, but that presynaptic Y1 receptors also exist. In conclusion, BIBP
      3226 has been shown to be an important tool for the elucidation of the
      physiological role of Y1 receptors in the cardiovascular system.

PMID- 8876039
TI  - Novel scaffolds for non-peptide mimetics of delta opioid receptor agonists based
      on peptide leads.

PMID- 8876040
TI  - Bradykinin receptors and receptor ligands (with special emphasis on vascular
      receptors).

PMID- 8876041
TI  - JMV641: a potent bombesin receptor antagonist that inhibits Swiss 3T3 cell
      proliferation.
AB  - The peptides of the bombesin family are involved in stimulation of mitogenesis in
      various cell lines, including cancerous cell lines. Bombesin receptor antagonists
      are of great interest to inhibit this proliferation. We have synthesized a potent
      bombesin receptor antagonist, e.g., compound JMV641 [H-DPhe-Gln-Trp-Ala-Val-Gly
      His-NH-*CH[CH2-CH(CH3)2]-**CHOH- (CH2)3-CH3 [*(S); **92% of (S) isomer], in which
      a pseudopeptide bond mimicking the transition state analogue replaced the peptide
      bond between the two C-terminal residues. This compound was highly potent to dose
      dependently inhibit binding of 125I-GRP to Swiss 3T3 cells (IC50 = 0.85 +/- 0.15
      nM) and bombesin-stimulated Swiss 3T3 proliferation (pA2 = 8.78). However,
      compound JMV641 can inhibit bombesin-induced AP-1 regulated genes that are
      nuclear messengers mediating the actions of signal transduction pathways
      stimulated by growth factors.

PMID- 8876042
TI  - Effects of amino acids on development in vitro of cleavage-stage bovine embryos
      into blastocysts.
AB  - Effects of amino acids on early bovine embryo development in vitro were examined
      using a chemically-defined, protein-free culture medium. Bovine embryos produced
      in vitro were cultured from 18 h to 72 h post insemination in a simple medium
      containing lactate as the only energy source except for the amino acid
      treatments. Subsequently, embryos were transferred to TCM-199 supplemented with
      serum for blastocyst development to substantiate their developmental competence.
      Treatments were: (1) non-essential amino acids from TCM-199 (NEA); (2) essential
      amino acids from TCM-199 (EA); (3) NEA+EA; (4) Eagle's minimum essential medium
      amino acids (MEM AA); (5) 11 amino acids present in HECM-6 (11 AA); and (6) 0.2
      mM glutamine (GLN). A higher proportion of embryos (percentage of inseminated
      ova) cleaved to the > or = 8-cell stage by 72 h post insemination in NEA (56.7%),
      EA (41.2%), 11 AA (40.3%) and GLN (51.1%) than in either NEA+EA (30.0%) or MEM AA
      (33.1%). However, after transfer to complex medium, embryos that had developed in
      EA, as well as those in MEM AA or NEA+EA, produced significantly fewer
      blastocysts (37.1%, 34.4% and 25.6% respectively) than those in NEA (56.7%), GLN
      (48.9%) or 11 AA (37.7%). The ability of blastocysts to hatch from their zonae
      pellucidae was also affected by amino acid treatment during cleavage stages. The
      present study indicated that the addition of NEA or GLN or 11 AA to a chemically
      defined culture medium during the cleavage phase of bovine embryo development
      increases their subsequent ability to reach the blastocyst stage. These data have
      implications for understanding the nutritional needs of bovine embryos produced
      in vitro and for optimizing the composition of culture media to support their
      development.

PMID- 8876043
TI  - Effects of interferon-tau and progesterone on oestrogen-stimulated expression of
      receptors for oestrogen, progesterone and oxytocin in the endometrium of
      ovariectomized ewes.
AB  - The effects of recombinant ovine interferon-tau (IFN-tau) and progesterone on
      oestrogen-stimulated expression of endometrial receptors for oestrogen (ER),
      progesterone (PR) and oxytocin (OTR) were determined in ovariectomized ewes.
      Cyclic ewes (n = 16) were ovariectomized and fitted with uterine catheters on Day
      4 of the oestrous cycle (Day O, oestrous) and assigned randomly in 2 x 2
      factorial arrangement to receive daily intrauterine injections of either
      recombinant ovine IFN-tau (roIFN-tau; 2 x 10(7) anti-viral units) or control
      proteins from Day 11 to Day 15 and 50 mg progesterone from either Day 4 to Day 10
      (E-P) or Day 4 to Day 15 (E+P). All ewes received 50 micrograms oestradiol-17
      beta on Days 13, 14 and 15 and were hysterectomized on Day 16. In control ewes,
      endometrial ER mRNA, PR protein and OTR density were greater in E-P- than E+P-
      treated ewes. In E-P ewes, roIFN-tau decreased oestrogen-stimulated increases in
      ER and OTR, but not PR expression compared with control ewes. In E+P ewes,
      endometrial ER mRNA and protein, PR mRNA and protein, and OTR levels were lower
      in roIFN-tau-treated ewes than control ewes. Immunoreactive ER and PR were absent
      in the endometrial luminal and superficial glandular epithelium of roIFN-tau
      compared with control ewes, but were present in the deep glandular epithelium and
      stroma regardless of steroid or protein treatment. These results indicate that
      progesterone affects oestrogen-induced increases in endometrial ER, PR and OTR
      expression in the PR+ deep glandular epithelium and stroma, whereas IFN-tau
      suppresses oestrogen-induced increases ER, PR and OTR expression in the PR-
      luminal and superficial glandular epithelium. These combined actions of IFN-tau
      and progesterone to suppress oestrogen-induced increases in endometrial OTR
      formation would prevent pulsatile production of luteolytic prostaglandin F2 alpha
      by the endometrium during early pregnancy.

PMID- 8876044
TI  - Interactions between nutrition, testosterone and inhibin in the control of
      gonadotrophin secretion in mature rams.
AB  - The role of negative feedback by two testicular hormones, testosterone and
      inhibin, in the gonadotrophin responses of mature male sheep to changes in
      nutrition was tested. Six days after castration, 24 Merino rams were assigned to
      groups that were fed either a diet that maintained their initial liveweight
      (Intermediate diet), or about half of the Intermediate diet (Low diet), or the
      Intermediate diet with a supplement of lupin grain (High diet). One week after
      the change of diet, all animals were given subcutaneous testosterone implants,
      providing plasma testosterone concentrations of 3.06 +/- 0.14 ng mL-1 (mean +/-
      s.e.m.; n = 24). The implants were left in place for 7 days, during which time
      all the rams were also injected subcutaneously with 2 mL steroid-free bovine
      follicular fluid (bFF) every 8 h, to provide inhibin at mean plasma
      concentrations of 0.40 +/- 0.04 ng mL-1 (n = 24; compared with 1.50 +/- 0.12 ng
      mL-1 when the animals were intact). Five days after castration, there were
      significant increases in the frequency of luteinizing hormone (LH) pulses (from
      1.83 +/- 0.23 to 17.3 +/- 0.96 pulses per 12 h; mean +/- s.e.m.; n = 24) and
      concentrations of FSH (from 0.45 +/- 0.07 to 14.19 +/- 2.7 ng mL-1; n = 24).
      Dietary treatment did not significantly affect these responses. Treatment with
      bFF and testosterone for 7 days reduced LH-pulse frequencies and follicle
      stimulating hormone (FSH) concentrations in all groups. The degree of reduction
      was least in the group on the High diet, for which the FSH concentration (6.49 +/
      1.96 ng mL-1) and frequency of LH pulses (7.00 +/- 2.31 pulses per 24 h) were
      significantly higher than those observed in the other groups. The mean frequency
      of LH pulses did not differ significantly between the Intermediate group (0.88 +/
      0.61 pulses per 24 h) and the Low group (0.25 +/- 0.25 pulses per 24 h).
      Similarly, FSH concentrations did not differ significantly between these two
      groups (1.78 +/- 0.46 for the Intermediate group v. 1.33 +/- 0.26 ng mL-1 for the
      Low group). It is concluded that there is no response to diet in the absence of
      testicular hormones and the effects of nutrition on LH secretion in castrated
      rams given exogenous testosterone and inhibin are similar to those observed in
      intact rams.

PMID- 8876045
TI  - Patterns of hormone secretion throughout pregnancy in the one-humped camel
      (Camelus dromedarius).
AB  - Peripheral serum samples were collected from 8 pregnant dromedary camels and
      hormone secretion patterns were examined at specific time intervals. Mean serum
      progesterone concentrations began to rise 3-4 days after ovulation and remained
      reasonably constant at 3-5 ng mL-1 for the first 90-100 days of gestation.
      Concentrations then showed a definite fall, but thereafter remained constant
      again at 2-4 ng mL-1 throughout the rest of pregnancy. In contrast, serum
      oestrogen concentrations showed pronounced fluctuations during the first 100 days
      of gestation. Mean oestradiol-17 beta concentrations increased at around Day 50
      to about 100 pg mL-1 and then remained relatively constant from Day 90 to Day
      300. Mean oestrone sulfate concentrations, however, showed two definite peaks in
      early gestation, each reaching about 10 ng mL-1, with the first peak occurring
      around Day 25 and the second peak around Day 75. Oestrogen production then
      remained fairly constant until around Day 300, after which concentrations of both
      oestrone sulfate and free oestradiol-17 beta rose steeply over the next 80 days
      to reach mean peak values of 46 ng ML-1 and 518.7 pg mL-1, respectively, at the
      time of parturition. Concentrations of 13,14 dihydro-15-keto prostaglandin F2
      alpha (PGFM) remained low and reasonably steady at 100-200 pg mL-1 during the
      first 320 days of pregnancy; thereafter, PGFM concentrations rose steeply over
      the next 50 days, before an explosive further increase to a peak of 1900 +/- 141
      pg mL-1 mean +/- sem on the day of calving. These results suggest that, as in the
      cow, a major change in steroid synthetic capability and/or enzyme content of the
      placenta may occur at around 80% (Day 300) of gestation in the pregnant camel.

PMID- 8876046
TI  - Effect of copper ion on the motility, viability, acrosome reaction and
      fertilizing capacity of human spermatozoa in vitro.
AB  - The objective of this study is to provide additional information on the effect of
      copper ion (Cu2+) in preventing pregnancy. Human spermatozoa, selected by the
      swim-up method, were incubated for 0, 5 or 24 h in the presence of 10 ng, 1
      microgram, 10 micrograms or 100 micrograms of Cu2+ mL-1 in BWW culture medium,
      and then evaluated in terms of their motility, viability, acrosome reaction (AR)
      and the capacity to penetrate zona-free hamster eggs. AR and penetration in zona
      free hamster eggs were assessed at 5 h of incubation. Motility, viability and AR
      in sperm incubated for 5 h were significantly affected by Cu2+ at a concentration
      of 100 micrograms mL-1, but not at the lower concentrations. Incubation for 24 h
      did not affect motility and viability of sperm incubated in the presence of
      concentrations of Cu2+ ranging from 10 ng mL-1 to 10 micrograms mL-1, but a
      concentration of 100 micrograms mL-1 caused a significant decrease in both
      parameters. In contrast, the penetration rate of zona-free hamster oocytes
      significantly decreased compared with that of controls, when only sperm were
      incubated in the presence of concentrations of Cu2+ ranging from 10 ng mL-1 to 10
      micrograms mL-1, and no penetration was observed in the presence of 100
      micrograms mL-1 of Cu2+ . When only oocytes were exposed to Cu2+, the penetration
      rate dropped to 50% of that of the controls. Finally, when both gametes were
      exposed to Cu2+ before co-incubation, the penetration rate fell to zero for every
      concentration tested. Results showed that copper, at concentrations similar to
      those released from intrauterine devices (IUD), affects the fertilizing capacity
      of human gametes in vitro and interferes with the sperm-oocyte interaction
      leading to fertilization. These effects suggest that the principle action of Cu2+
      released from Cu-IUD is to act as a preconception contraceptive agent when
      delivered in endometrial and oviducal fluids.

PMID- 8876047
TI  - Aromatase activity of ovine follicular walls: technical validation and
      physiological control.
AB  - Since aromatase activity quickly disappears in cultured sheep granulosa cells,
      its control is poorly understood. As a result, an aromatase assay was developed
      using cultures of follicular walls and measuring the amount of 3H2O generated
      from 3H-testosterone. Chromatography and mass spectrometry analysis demonstrated
      that 3H2O production was indeed associated with the production of oestradiol-17
      beta. Optimization of the assay demonstrated: (1) a steady increase in the amount
      of 3H2O produced over at least 12 h; and (2) highly significant correlations
      between the amounts of 3H2O measured and the weight of the follicular wall or the
      amount of 3H-testosterone provided. Furthermore, a highly significant correlation
      (r = 0.82) was observed between the amount of 3H2O produced and the concentration
      of oestradiol in the same samples. The effects of follicle-stimulating hormone
      (FSH), luteinizing hormone (LH) and oestradiol on aromatization by follicles at
      two specific stages of maturation (recruitment, 12 h after luteolysis; dominance,
      36 h after luteolysis) were then assessed. At recruitment and dominance, FSH was
      able to modulate aromatase activity similarly, increasing and decreasing the
      activity at low concentrations and high concentrations respectively. At
      recruitment and dominance, oestradiol had no stimulatory effect on basal
      aromatase activity and even blocked the stimulatory effects of FSH on aromatase
      at recruitment. LH significantly inhibited the FSH-stimulated aromatase activity
      of dominant follicles. It is concluded that: (1) FSH may induce the recruitment
      of follicles by increasing aromatase activity; and (2) neither oestradiol nor LH
      stimulate the aromatase activity of follicles which could explain maintenance of
      the dominant follicle.

PMID- 8876048
TI  - The collagen skeleton of the human umbilical cord at term. A scanning electron
      microscopy study after 2N-NaOH maceration.
AB  - The organization of the collagen fibrils in the human umbilical cord at term is
      directly visualized by means of a scanning electron microscopy cell maceration
      method. This technique clearly reveals that there is a much more extensive
      collagen fibrillar architecture within the umbilical cord than that reported in
      the classical histological descriptions. The Wharton's jelly, in fact, appears as
      a spongy network of interlacing collagen fibres and small woven bundles
      apparently arranged at random and forming a continuous soft skeleton that encases
      the umbilical vessels. The collagen fibrillar network shows the presence of a
      wide system of interconnected cavities consisting of canalicular-like structures
      as well as cavernous and perivascular spaces. This system of cavities might play
      a mechanical role allowing the storing of the ground substance of the jelly and
      its diffusion during twisting or compression. Furthermore, it may have an
      important role facilitating the diffusion throughout the jelly of diffused
      materials (i.e. water and trophic metabolites) either from or to the umbilical
      vessels and the amniotic cavity, thus overcoming the lace of a proper vasculature
      with the jelly.

PMID- 8876049
TI  - Urinary excretion of prostacyclin in a rat model of uteroplacental vasculature
      occlusion: implications for fetal growth retardation.
AB  - An experimental model was devised in the pregnant rat to study by a combined high
      pressure liquid chromatography and radioimmunoassay technique the accumulation of
      prostanoids (PNs) in the urine after transient-complete or permanent-partial
      interruption of the maternal-fetal blood flow. After 8 min of complete
      restriction of the blood flow in the pregnant rat at 18 days of gestation, the
      urinary concentration of 6-keto-prostaglandin F1 alpha (6k-PGF1 alpha, the stable
      prostacyclin metabolite) increased from 4.97 +/- 1.27 ng mg-1 creatinine to 8.09
      +/- 2.47 ng mg-1 creatinine and 13.02 +/- 4.5 ng mg-1 creatinine after the second
      and third post-operative day respectively. The urinary concentration of the 2,3
      dinor derivative of prostacyclin reached 12.35 +/- 5.44 ng mg-1 creatinine after
      the second post-operative day and was reduced to 4.71 +/- 1.94 ng mg-1 creatinine
      after the third post-operative day. The concentration of thromboxane B2 (TxB2,
      the stable thromboxane A2 metabolite) increased approximately 7-fold and 13-fold
      over that of the control after the second and third post-operative day
      respectively. The urinary concentration of the 2,3-dinor derivative of TxB2 (d
      TxB2) increased from about 1.42 +/- 0.3 ng mg-1 creatinine to 4.49 +/- 0.9 ng mg
      1 creatinine and 7.76 +/- 2.63 ng mg-1 creatinine under the same experimental
      conditions. Increases in the urinary concentrations of 6k-PGF1 alpha and d-TxB2
      to 94 +/- 27.76 ng mg-1 creatinine and 12.05 +/- 2.26 ng mg-1 creatinine,
      respectively, were observed on the second post-operative day, after the
      restriction time was increased to 30 min. Permanent-partial occlusion of the
      maternal fetal circulation resulted in excretion of PNs in the urine to similar
      levels produced after transient-complete restriction. High concentrations of
      prostacyclin (range, 0.8 ng min-1 mg-1 wet weight) were produced in vitro by
      uterine preparations from restricted animals after the second post-operative day.
      Placenta preparations from restricted animals generally exhibited a lower ability
      to synthesize PNS (up to 0.006 ng min-1 mg-1 wet weight) compared with uterine
      tissue but produced more thromboxane than their sham counterparts. The data
      suggest that the uterus constitutes the main source for urinary PN excretion
      following short episodes of maternal-fetal blood flow interruption.

PMID- 8876050
TI  - Morphological changes in the oesophagus of newborn pigs: effects of age, diet and
      oral insulin-like growth factor I (IGF-I) or IGF-II.
AB  - It has been reported in the literature that the stomach and the intestine in
      newborns undergo profound growth and functional maturation during the immediate
      postnatal period and diet ingestion has a significant impact on these changes.
      The present paper examines oesophageal development in newborn pigs during the
      first three postnatal days and the effects of diet and oral insulin-like growth
      factor I (IGF-I) or IGF-II on oesophageal morphology. It was observed that marked
      changes, including reduction in thickness of the epithelium, accelerated
      proliferation and migration of basal epithelial cells and increased accumulation
      of mucus in the glandular cells, occurred during the first postnatal day
      following onset of natural suckling. Bottle-feeding with various liquid diets
      (i.e. porcine colostrum, bovine colostrum, bovine milk, and infant milk formula),
      induced marked morphological changes which were similar to those induced by
      natural suckling. However, bottle-feeding with water did not result in marked
      reduction in the thickness of the epithelium nor did it accelerate basal
      epithelial cell proliferation and migration. Oral IGF-I, but not IGF-II,
      increased basal epithelial cell proliferation up to 81%. Owing to a large inter
      animal variation, the increment did not reach a significant level (P = 0.071).
      The results suggest that chemical constituents in the diet and physical
      stimulation of food ingestion, which cause sloughing off of luminal surface
      tissue, are two major stimuli or epithelial cell proliferation in the new born
      oesophagus.

PMID- 8876051
TI  - Intracellular pH monkey embryos at various stages of organogenesis estimated by
      dimethadione distribution.
AB  - Previous experiments using the transplacental distribution of 14C-DMO (5,5
      dimethyloxazolidine-2,4-dione or commonly known as dimethadione) have
      demonstrated that the pH of rat embryos and fluids progressively decreases during
      organogenesis. The aim of the present experiments was to similarly evaluate pH
      changes during organogenesis in the cynomolgus monkey, which is a model for human
      embryogenesis. Using DMO quantitated by gas chromatography-mass spectrometry as
      opposed to the counting of radiolabelled compound, cynomolgus monkey embryos were
      determined to undergo a similar decrease in embryonic pHi over an approximately
      comparable period of development (Days 24-36 of gestation). The ratio of DMO in
      chorionic fluid to DMO in maternal plasma in the cynomolgus monkey also displayed
      a decrease with advancing gestational age indicative of a pH decrease. The DMO
      transplacental distribution was found to be significantly slower in the
      cynomolgus monkey than that in rodents. The present investigation indicates that
      the magnitude of the reduction of pH in embryonic cells and in extra-embryonic
      fluids over a period of organogenesis in the cynomolgus monkey is similar to the
      reduction detected in rodent embryos and fluids over a comparable developmental
      period, but the relative gradient between maternal blood pH and embryonic
      intracellular pH is different. The difference in the pH gradient between the two
      species may lead to differential transplacental distribution of exogenous and
      endogenous substances.

PMID- 8876052
TI  - Effects of calcium channel blockers on spontaneous electrical activity of freshly
      isolated three-day-old embryonic chick ventricle.
AB  - The effects of four major types of organic Ca2+ channel blockers, verapamil,
      nifedipine, diltiazem and fendiline and of tetrodotoxin (TXX), a fast Na+ channel
      blocker, on the action potential (AP) of freshly isolated 3-day-old embryonic
      chick ventricle (3d ECV) were investigated to resolve the controversy about the
      ionic basis of upstroke. The APs were characterized by a maximum diastolic
      potential (MDP) of -60 mV, an overshoot (Eov) of 16 mV and a maximum upstroke
      velocity (+Vmax) of 42 V s-1. All four Ca2+ channel blockers (0.1-40 microM) and
      TTX (0.1-80 nM) produced a dose-dependent reduction in +Vmax and Eov. MDP was
      also reduced by Ca2+ channel blockers in a dose-dependent manner but was
      unaffected by TTX. A significant linear correlation between MDP and +Vmax was
      observed for verapamil (r = 0.99), nifedipine (r = 0.99), diltiazem (r = 0.96)
      and fendiline (r = 0.98). Surprisingly, all Ca2+ channel blockers produced a dose
      dependent positive chronotropic effect leading to cessation of firing at high
      doses (20-40 microM). In preparations becoming quiescent with high doses of
      verapamil (20-40 microM), elevated extracellular concentrations of Ca2+ (up to
      9.6 nM) and isoproterenol (0.5-40 microM) failed to restore spontaneous APs.
      Electrical stimulation also failed to elicit APs in preparations inhibited by
      verapamil, diltiazem and fendiline. The inhibition of +Vmax by TTX demonstrates
      that fast Na+ channels were involved in the upstroke of AP in 3d ECV. Voltage
      dependent inactivation of fast Na+ channels during depolarization (reduction in
      MDP) by the Ca2+ channel blockers explains their inhibitory effect on +Vmax and
      indicates that L-type Ca2+ channels had no significant role in the upstroke. A
      positive chronotropic effect of the Ca2+ channel blockers further suggests that
      slow Ca2+ channels are not involved in automaticity in freshly isolated 3d ECV.

PMID- 8876053
TI  - Localization by indirect immunofluorescence of nitric oxide synthase in mouse and
      human spermatozoa.
AB  - The localization of nitric oxide synthase was studied in mouse epididymal
      spermatozoa and freshly ejaculated human sperm. A rabbit antiserum against the
      neuronal isoform of the enzyme was used, and antibody binding was detected with a
      fluorescein isothiocyanate-conjugated polyclonal antibody specific for rabbit
      IgG. In mouse spermatozoa, the percentage of cells staining specifically ranged
      from 88% to 98%. Samples were examined after 0-, 90- and 150-min incubations in
      vitro. Three different patterns of staining were observed: (a) Pattern I, intense
      fluorescent staining localized in the acrosome and in a segment of the tail; (b)
      Pattern II, fluorescent staining localized only in the tail; and (c) Pattern III,
      faint fluorescent staining localized in the acrosomal cap and in the tail. The
      potential physiological significance of these patterns is discussed. Nitric oxide
      synthase was also localized in the acrosome of freshly ejaculated human sperm.

PMID- 8876054
TI  - Introduction: novel specific immunity functioning alongside classical specific
      immunity.

PMID- 8876055
TI  - Origin and evolution of the class I gene family: why are some of the mammalian
      class I genes encoded outside the major histocompatibility complex?

PMID- 8876056
TI  - Evidence foe antigen presentation by the class Ib molecule, Qa-1.

PMID- 8876057
TI  - Multiple products of class Ib Qa-2 genes which ones are functional?

PMID- 8876058
TI  - Antigen-presenting function(s) of the non-classical HLA-E, -F and -G class I
      molecules: the beginning of a story.

PMID- 8876059
TI  - Crystal structure of the MHC class Ib molecule H2-M3.

PMID- 8876060
TI  - CD1: clues on a new antigen-presenting pathway.

PMID- 8876061
TI  - The MIC gene family.

PMID- 8876062
TI  - The structure and evolution of FcRn.

PMID- 8876063
TI  - Stimulation of gamma delta T cells by phosphoantigens.

PMID- 8876064
TI  - Direct presentation of non-peptide prenyl pyrophosphate antigens to human gamma
      delta T cells.

PMID- 8876065
TI  - Review of the functional anatomy of the cartilages and muscles of the nose.
AB  - This paper reviews the anatomy of the nasal cartilages and muscles. Accurate
      anatomical knowledge of these structures may facilitate the design of a model to
      study the mobility and support of the lateral nasal wall and ala and may thus
      provide information on the dynamics of valve area. It is concluded that a uniform
      description of nasal cartilages and muscles is still lacking. This is especially
      true for the attachments of the nasal cartilages to neighbouring structures, as
      well as the location and function of the muscles influencing the valve area. The
      use of uniform, preferably anatomical, terminology is encouraged.

PMID- 8876066
TI  - The effect of changes in ambient temperature on the reliability of acoustic
      rhinometry data.
AB  - The effect of changing ambient temperature on the reliability of acoustic
      rhinometer data was examined. The acoustic rhinometer was set up in a climate
      chamber, and connected to a simple cylindrical model containing a constriction.
      This constriction was at 22.5 cm from the microphone. This would be the position
      of the tip of a 7.5-cm nose piece, relative to the microphone, when attached to
      the rhinometer. The ambient temperature was increased from 10 degrees C to 40
      degrees C. The position of the constrictions as recorded by the acoustic
      rhinometer was compared in the same stable model at intervals during the
      temperature increase. The point of identification of the constriction varied with
      ambient temperature and the change almost perfectly followed the expected changes
      in the readings given the relationship of the speed of sound in air to ambient
      temperature. A shift of approximately 1 mm along the X-axis per 2.5 degrees C
      change in temperature is seen for this constriction. In a human subject the whole
      acoustic rhinometry trace would shift along the X-axis to the same degree when
      using a 7.5-cm nose piece. Volume estimates are calculated between two fixed
      points on the X-axis and may be profoundly affected by even a small shift of the
      acoustic reading along this axis. Acoustic rhinometry data should always be
      collected under the same stable environmental conditions.

PMID- 8876067
TI  - Growth characteristics of the human nasal septum.
AB  - Using a specially designed algorithm for the measurement of the surface area of
      shapes with highly irregular contours, growth curves were developed for post
      natal septal growth in humans using post-mortem specimens of a study population
      of 30 cases, distributed over the age range from birth to 62 years. From the
      results a rapid growth phase for the total septum is evident immediately after
      birth, lasting until the second year of life. Then, a gradual deceleration of
      growth is recognized with a plateau eventually being reached at the age of 36
      years. Mathematical analysis of the growth curve shows that the curve for the
      total septum is the sum of two separate mathematical equations, representing the
      cartilaginous and bony contribution, respectively. It is demonstrated that the
      cartilaginous septum reaches adult dimensions (lateral surface area) at the age
      of two years. Subsequent growth of the septum is due to expansion of the
      perpendicular plate, i.e. the bony parts of the septum.

PMID- 8876068
TI  - A probe holder for precise intranasal microcirculation measurements.
AB  - A probe holder for long-term measurements of intranasal microcirculation by laser
      Doppler flowmetry is described. It is adjustable to any physiognomy and allows
      precise intranasal probe insertion. It is based on a commercially-available
      shooting-spectacles frame and might also be useful for other measurements such as
      intranasal temperature, humidity and pO2.

PMID- 8876069
TI  - Nasal provocation test in the diagnostics of occupational allergic rhinitis.
AB  - The diagnosis of occupational rhinitis (OR) must be better confirmed than in
      allergic rhinitis of other aetiology. A provocation test is required to confirm
      the causality between the disease and the work exposure. The purpose of this
      study has been to examine the feasibility of active anterior rhinomanometry and
      visual analogue scale in the diagnostics of OR, and to compare the results of
      these measurements to a nasal status change score. The study subjects have been
      50 consecutive patients suspected of having OR. Altogether 148 bilateral nasal
      provocation tests (NPTs), 55 placebo- and 93 allergen-NPTs, have been done. Based
      on the change in the nasal status and change in the nasal airway resistance
      (NAR), there are 42 positive NPTs. Although overlapping between placebo and
      allergen provocations exists, an increase of > 50% in NAR is recommended to
      regard the result as positive in NPT. The evaluation of the nasal reaction in the
      NPT is mainly based on anterior rhinoscopy and the change in the status score,
      but OR diagnostics should also include some physiological measurement.

PMID- 8876070
TI  - Cetirizine and pseudoephedrine retard alone and in combination in the treatment
      of perennial allergic rhinitis: a double-blind multicentre study.
AB  - We compared the efficacy and safety of 5 mg cetirizine (CTZ), 120 mg
      pseudoephedrine retard (PER) and their combination (COM), given twice daily for
      three weeks, for the treatment of perennial allergic rhinitis. Two hundred and
      ten evaluable patients (97 males and 113 females) were included in the study and
      randomly allocated to one of three treatment groups, each of 70 patients. Nasal
      obstruction, sneezing, rhinorrhoea, nasal and ocular pruritus were scored each
      day throughout the study by patients using a symptom scale ranging from 0 (no
      symptom) to 3 (severe). The mean proportion of days without symptoms was higher
      in the COM group (11.8%) than in the CTZ (6.8%) and PER (5.1%) groups, but the
      differences were not statistically significant. The mean percentage of days when
      symptoms were absent or at most mild was significantly higher in the COM group
      (64.8%) than in either CTZ (45.5%; p = 0.003) or PER groups (40.6%; p = 0.0001).
      In addition, evaluation of symptoms by investigators and their global evaluation
      at the end of treatment showed statistically significant differences in favour of
      COM compared, to both CTZ and PER. The most frequent adverse events were
      somnolence in the CTZ and COM groups (8.6% and 12.9%, respectively) while
      insomnia was most frequent in the PER group. No clinically significant
      abnormalities were found in haematological or biochemical tests. These results
      indicate that the combined treatment was more effective than and as well
      tolerated as treatment with each individual agent.

PMID- 8876071
TI  - An international comparison of characteristics of the sensation of nasal
      obstruction between Canadian and Japanese patients.
AB  - To determine differences in perception of nasal obstruction in Canadians and
      Japanese, we assessed subjective and objective nasal patency of 48 patients in
      Canada and 43 patients in Japan. Mean severity of the sensation of nasal
      obstruction in Canadian patients was significantly higher than in Japanese
      patients, while no significant differences in nasal resistances were found.
      Complaints of nasal obstruction in Canadian patients were directly concerned with
      nasal breathing, while Japanese patients complained of indirect matters, such as
      "unable to concentrate on job or study" or "nasal obstruction or nasal speech
      pointed out by other persons." The differences might be due to national
      characteristics.

PMID- 8876072
TI  - Comparison of mizolastine with loratadine in the treatment of perennial allergic
      rhinitis.
AB  - Mizolastine is a new, non-sedating antihistamine providing satisfactory
      symptomatic relief in seasonal allergic rhinitis. The purpose of this study has
      been to compare mizolastine to loratadine in perennial allergic rhinitis. This
      multicentre, double-blind study has involved 68 patients, randomly allocated,
      after a one-week placebo run-in, to 10 mg mizolastine or 10 mg loratadine, both
      given on a once-daily basis, for four weeks. Comparable symptom relief occurs in
      both groups resulting, respectively for mizolastine and loratadine, in a 66.6%
      and a 61.3% decrease in total nasal score, to a 74.8% and a 76.4% decrease in
      total ocular score, and to a 69.0% and a 64.8% decrease in global total score.
      Safety is satisfactory in both groups. Mizolastine is at least as effective as
      loratadine in relieving perennial allergic rhinitis symptoms and its safety
      profile allows its use in the treatment of this disease.

PMID- 8876073
TI  - Exudation into the nasal cavity of carbon particles injected into nasal polyps.
AB  - A colloidal carbon solution was prepared by dissolving 50 mg of ultra fine carbon
      particles (diameter: 21-50 nm) and polyvinylpyrrolidone-- for stabilizing the
      dispersion--in 1 ml physiological saline, and injected into the nasal polyps of
      allergic patients. Two hours after injection, the nasal polyps were removed and
      examined by transmission electron microscopy. Notably, carbon particles could not
      pass through the epithelial basement membrane and were therefore not observed
      between the epithelial cells, where no inflammatory cells infiltrated the
      epithelial layer. However, they passed through the fissure in the basement
      membrane, which was formed by the penetration of inflammatory cells (eosinophils)
      into the epithelial layer. Many carbon particles were observed in the
      interstitial space of the epithelial layer, where a large number of inflammatory
      cells accumulated. Furthermore, they passed into the nasal cavity along with the
      interstitial mucous fluid through the opened epithelial junction. A wide pathway
      from the submucosa to the nasal cavity, through which large-sized particles can
      pass, was demonstrated in the polyp's mucosa. Moreover, as carbon particles
      exhibit no chemotaxis, they must move according to the interstitial fluid flow,
      which suggests that the interstitial fluid flows outwardly from the mucosa during
      allergy.

PMID- 8876074
TI  - Radical or partial maxillary sinus surgery: a dilemma today? An experimental
      study.
AB  - To evaluate partial or radical surgical removal of the maxillary sinus mucosa, 20
      New-Zealand albino rabbits were used. After three months, specimens were taken
      for examination. Bacteriological cultures, light- and electron microscopy were
      performed, and mucociliary transport was studied. These experimental findings add
      further support to the concept of performing a conservative sinus procedure
      rather than a radical removal as a first procedure.

PMID- 8876075
TI  - Inverted papilloma: incidence and late results of surgical treatment.
AB  - The 452,000 inhabitants of the County of Funen are considered to constitute a
      representative section of the population of Denmark. The county is geographically
      well-defined, surrounded by sea. Specimens from the two Departments of Pathology
      in the county have been histologically reviewed. Our incidence material consists
      of 96 patients suffering from inverted papillomas, during a 14-year period, which
      corresponds to 1.5 cases per 100,000 inhabitants per year. During the same 14
      year period, 67 patients have been operated upon at the ENT Department of Odense
      University Hospital. In 1992, a clinical re-examination was performed regarding
      late surgical results. Fourteen per cent (9/67) have developed recurrences from 6
      to 56 months after the first operation. No major late surgical complications have
      been observed. It is our experience that lesions limited to the nasal septum and
      minor lesions on the lateral nasal wall can be treated primarily by an intranasal
      procedure. Large lesions on the lateral wall with best results have been treated
      by lateral rhinotomy.

PMID- 8876076
TI  - Combined endonasal and percutaneous endoscopic approach to Pott's puffy tumour.
AB  - The most favourable management of frontal sinus disease and its complications
      involves the choice of the least invasive operative technique likely to eradicate
      the disease process. With the introduction of endonasal endoscopic surgery,
      examination of the frontal recess and removal of obstructive ethmoidal cells or
      diseased mucosa becomes feasible. Percutaneous frontal sinus endoscopy
      facilitates sinus irrigation, thorough inspection of the frontal sinus, removal
      of diseased mucosa within the frontal sinus, and evacuation of subperiosteal
      abscesses. Six cases of Pott's puffy tumour secondary to frontal sinusitis
      treated by combined endonasal and percutaneous endoscopic surgery are presented.
      CT scan is diagnostic for associated complication and underlying pathology.
      Complications are minimal. Combined endonasal and percutaneous endoscopic surgery
      is a good approach which can be carried out for the treatment of frontal sinus
      diseases and its complications.

PMID- 8876077
TI  - Diagnosis and treatment of sinusitis by YAMIK sinus catheters.

PMID- 8876078
TI  - The first naso-sinus laboratory for cadaver preparation in Thailand.
AB  - The first naso-sinus laboratory has been set up in Siriraj Hospital for better
      training of rhinosurgeons. The specimens used for practice operation are the
      entire nasal cavities with all paranasal sinuses, taken from cadavers and
      preserved in 95% ethanol. The "Siriraj" sinus holder is specially designed and
      constructed to hold various sizes of specimens. It is made of plastic board and
      stainless steel screws; it is an inexpensive and simple device which can be
      afforded by every centre. With this naso-sinus laboratory, ENT residents and
      rhinosurgeons can achieve their skills in performing nasal endoscopy, endoscopic
      or microscopical sinus surgery and all kinds of sinus operations at their
      convenience.

PMID- 8876079
TI  - Effects of physical exertion on task performance in modern manufacturing: a
      taxonomy, a review, and a model.
AB  - Modern manufacturing systems have the characteristic of demanding human cognitive
      task performance in an environment where sudden physical demands are also
      possible. There is little research addressing the effects of physical work on
      cognitive task performance and it is not well organized for application to
      manufacturing systems design. This paper uses an initial three-dimensional
      taxonomy to review the literature. Some clear findings emerge, but many studies
      produced contradictory results. While part of the contradiction was due to
      experimental technique, some was also due to the lack of a detailed structure to
      guide future research. Such a model is thus proposed, using the concept of
      limited resources for both the cognitive and physical aspects of tasks. In
      addition, specific predictions of research needs for modern manufacturing systems
      arise.

PMID- 8876080
TI  - Rating of acceptable load in manual sorting of postal parcels.
AB  - The psychophysical test, the rating of acceptable load (RAL) were used to assess
      acceptable weights for dynamic lifting in postal workers engaged in sorting
      parcels. The standard test (RALSt) and a work-simulating test (RALW) were
      administered to 103 volunteers: all experienced male sorters. In the RALSt,
      subjects selected the weight which would be acceptable for lifting in a box with
      handles from table to floor and back to the table once every 5 min for the
      working day. for the RALW, the box was without handles and the weight was chosen
      to be acceptable for transfer 4-6 times/min from a table to the parcel container
      and back to the table. Both tests were made during normal working hours at postal
      sorting centres. The overall means for RALSt and RALW were 16.4 kg and 9.4 kg
      respectively (p < 0.001): both being substantially higher than the average parcel
      weight of 4 kg. The RALSt and RALW tests proved to be repetitive and sensitive
      for differentiating the effects of load and task variable in actual manual
      material handling. Thus they appear to be applicable to the evaluation of manual
      materials handling problems.

PMID- 8876081
TI  - Congenital anterior abdominal wall defects.

PMID- 8876082
TI  - Intracoronary stents.

PMID- 8876083
TI  - Lactational amenorrhoea method for family planning.

PMID- 8876084
TI  - Barriers to evidence based policy.

PMID- 8876085
TI  - Drug delivery from inhaler devices.

PMID- 8876086
TI  - Cancer registration: integrate or disintegrate?

PMID- 8876087
TI  - Widow backed in legal fight for husband's sperm.

PMID- 8876088
TI  - Flu jab cuts hospital admissions by two thirds.

PMID- 8876089
TI  - Shooting the messenger.

PMID- 8876090
TI  - Congenital anterior abdominal wall defects in England and Wales 1987-93:
      retrospective analysis of OPCS data.
AB  - OBJECTIVES: Analysis of incidence and characteristics of congenital abdominal
      wall defects, with special reference to the differences between the incidence of
      gastroschisis and exomphalos (omphalocele). DESIGN: Retrospective analysis using
      data from the Office of Population Censuses and Surveys (recoded to differentiate
      exomphalos and gastroschisis) and the National Congenital Malformation
      Notification Scheme. SETTING: England and Wales, 1987 to 1993. RESULTS: 1043
      congenital anterior abdominal wall defects were notified within the seven year
      study period. Of these, 539 were classified as gastroschisis, 448 as exomphalos,
      19 as "prune belly syndrome," and 37 as "unclassified." Gastroschisis doubled in
      incidence from 0.65 in 1987 to 1.35 per 10,000 total births in 1991, with little
      further change; the incidence of exomphalos decreased from 1.13 to 0.77 per 10000
      births. The overall incidence of notified congenital abdominal wall defects was
      2.15 per 10000 total births. Gastroschisis was associated with a lower overall
      maternal age than exomphalos and with a significantly lower proportion of
      additional reported congenital malformations (5.0%) than in the cohort with
      exomphalos (27.4%) (odds ratio 0.14, 95% confidence interval 0.09 to 0.22; P <
      0.001). The sex ratio of the two cohorts was the same. The incidence of
      gastroschisis and exomphalos was higher in the northern regions of England than
      in the south east of the country. CONCLUSIONS: The national congenital
      malformation notification system showed an increasing trend in the incidence of
      fetuses born with gastroschisis and a progressive decreasing incidence of
      exomphalos in England and Wales between 1987 and 1993. Although the reasons for
      this are likely to be multifactorial, a true differential change seems likely.
      The observed increase in incidence of gastroschisis relative to exomphalos and
      the differentiation in maternal age have implications for resource management
      within the NHS and warrant further epidemiological monitoring. Regional
      differences may be due to a dietary or environmental factor, which requires
      further study.

PMID- 8876091
TI  - Life expectancy in men who have never smoked and those who have smoked
      continuously: 15 year follow up of large cohort of middle aged British men.
AB  - OBJECTIVE: To estimate the life expectancy in a representative sample of men who
      have never smoked and of those who have smoked all their adult lives. DESIGN: 15
      year follow up of a large representative cohort of British men in the British
      regional heart study and use of national mortality statistics for 1992. SUBJECTS:
      7735 middle aged British men aged 40-59 at the time of screening (between 1978
      and 1980). MAIN OUTCOME MEASURES: Mortality from all causes and from smoking
      related causes. RESULTS: 1624 men had never smoked at the time of screening and
      did not take up smoking during the study. 127 of them died during follow up. 3151
      men began smoking before they were 30 and were still smoking at the time of
      screening. Of these, 751 had stopped smoking five years after screening; they
      were excluded from the analysis five years after the date they had stopped. 560
      of the lifelong smokers died during follow up. When study estimates were combined
      with those from national mortality statistics for men aged 20-40, only an
      estimated 42% (95% confidence interval 36% to 50%) of lifelong smokers alive at
      the age of 20 would be alive at 73, compared with 78% (74% to 82%) of lifelong
      non-smokers. CONCLUSION: These estimates present the effects of smoking on
      mortality in a way that is easily communicated to patients and the general public
      in health promotion initiatives.

PMID- 8876092
TI  - Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila,
      the Philippines: non-comparative prospective trail.
AB  - OBJECTIVE: To determine the contraceptive efficacy of the lactational amenorrhoea
      method. DESIGN: Non-comparative prospective trial. SETTING: Urban Manila, the
      Philippines. SUBJECTS: 485 lower income, educated women with extensive experience
      of breast feeding. INTERVENTION: Women were offered all available contraceptives
      for use after birth. Those who chose the lactational amenorrhoea method were
      taught the method, screened for the study, and followed for 12 months to
      determine the risk of pregnancy when the method was used. MAIN OUTCOME MEASURES:
      Life table pregnancy rates during correct and incorrect use of the method,
      censored monthly in the event of sexual abstinence or the use of another
      contraceptive method. RESULTS: The lactational amenorrhoea method was 99%
      effective when used correctly (that is, during lactational amenorrhoea and full
      or nearly full breast feeding for up to six months). At 12 months the
      effectiveness during amenorrhoea dropped to 97%. CONCLUSIONS: The lactational
      amenorrhoea method provided as much protection from pregnancy as non-breast
      feeding women experience with non-medicated intrauterine devices and barrier
      methods. The contraceptive effect of lactation cannot be attributed to
      lactational or postpartum abstinence.

PMID- 8876093
TI  - Effectiveness of the BBC's 999 training roadshows on cardiopulmonary
      resuscitation: video performance of cohort of unforewarned participants at home
      six months afterwards.
AB  - OBJECTIVE: To examine the competence of a cohort trained in cardiopulmonary
      resuscitation by the BBC's 999 training roadshows. DESIGN: Descriptive cohort
      study applying an innovative testing procedure to a nationwide systematic sample.
      The test sample received an unsolicited home visit and without warning were
      required to perform cardiopulmonary resuscitation on a manikin while being
      videoed. The videos were then analysed for effectiveness and safety using the new
      test. SETTING: Nine cities and surrounding areas in the United Kingdom. SUBJECTS:
      280 people aged between 11 and 72. RESULTS: Thirty three (12%) trainees were able
      to perform effective cardiopulmonary resuscitation, but of these 14 (5%)
      performed one or more elements in a way that was deemed to be potentially
      injurious. Thus only 19 (7%) trainees were able at six months to provide safe
      cardiopulmonary resuscitation. In addition, large numbers of subjects failed to
      shout for help, effectively assess the status of the patient, or alert an
      ambulance. Significantly better performances were recorded by those under 45
      years old (31 (14%) v 2 (4%) gave effective performances respectively, P < 0.05),
      those who had attended a subsequent cardiopulmonary resuscitation course (8 (40%)
      v 25 (10%) gave effective performances respectively, P < 0.0001), and those
      confident in their initial ability (26 (20%) v 7 (6%) gave effective performances
      respectively, P < 0.005). Females were significantly less likely than males to
      perform procedures in a harmful way (117 (62%) v 10 (12%) performed safely
      respectively, P < 0.005). CONCLUSION: Television is an effective means of
      generating large training cohorts. Volunteers will cooperate with unsolicited
      testing in their home, such testing being a realistic simulation of the stress
      and lack of forewarning that would surround a real event. Under such conditions
      the performance of cardiopulmonary resuscitation was disappointing. However,
      retraining greatly improves performance.

PMID- 8876094
TI  - House dust mite allergen in pillows.

PMID- 8876095
TI  - Improving uptake of prophylaxis for venous thromboembolism in general surgical
      patients using prospective audit.

PMID- 8876096
TI  - Continuing medical education and training for associate specialists: results of a
      survey in Yorkshire.

PMID- 8876097
TI  - Postal questionnaire study of disability in the community associated with
      psoriasis.
AB  - OBJECTIVE: To study the disability caused by psoriasis in patients recorded as
      having psoriasis by their general practitioner. DESIGN: Postal questionnaire
      survey using the psoriasis disability index and SF-36. SETTING: Five general
      practices in Cleveland. SUBJECTS: Of 767 patients identified, 546 completed the
      questionnaire and 435 were eligible and gave informed consent. MAIN OUTCOME
      MEASURES: Scores on SF-36 and psoriasis disability index. RESULTS: The psoriasis
      disability index score was highly negatively correlated with all eight of the SF
      36 health measures (P < 0.0001 for each), and the manual social classes scored
      higher than the non-manual social classes (P < 0.0001). The manual social class
      group scored significantly lower scores than the controls on all the SF-36
      scales, and the non-manual group scored significantly lower for physical and
      mental role limitation (P < 0.0004 and P = 0.026), mental health (P < 0.0001),
      energy and vitality (P < 0.0004), and health perception (P < 0.0001). Also, the
      manual group had poorer health perception on five of the SF-36 variables when
      compared with the non-manual group. CONCLUSIONS: Patients with psoriasis have an
      overall lower perception of their quality of life than healthy controls, and
      those in the lower social classes suffer a greater degree of disability from
      their disease than the higher social classes.

PMID- 8876098
TI  - Relation between general practitioners' prescribing of antibacterial drugs and
      their use of laboratory tests.

PMID- 8876099
TI  - Collecting ethnic group data for inpatients: is it useful?
AB  - Since April last year British hospitals have had to collect data on the ethnic
      group of every patient. Patients must categorise their own ethnic group using the
      categories of the 1991 census. Claire Hilton argues that such data collection is
      unhelpful and will not meet its stated aim of helping to provide equitable access
      to NHS services for all ethnic groups. Self categorisation is unreliable, and the
      number of ethnic groups available is inadequate, in particular for the white
      population. Additional data on the size of each ethnic group in the local
      population and on rates of illness in particular groups are necessary to assess
      whether services are being provided equitably. Moreover, ethnicity is a
      multidimensional concept, and information on patients' language and cultural and
      religious practices, as well as their place of origin, is necessary if services
      are to be culturally sensitive.

PMID- 8876100
TI  - Methadone maintenance and tuberculosis treatment.

PMID- 8876101
TI  - Aids to compliance with medication.
AB  - Elderly people may need to take several forms of medication, including tablets
      and capsules, inhalers, insulin, and eye drops. This article describes various
      aids that are designed to facilitate compliance.

PMID- 8876102
TI  - Passive smoking and health: should we believe Philip Morris's "experts"?

PMID- 8876103
TI  - ABC of work related disorders. Assessing fitness for work.

PMID- 8876104
TI  - Home ventilation of a child with motor and sensory neuropathy. Life does have a
      price, and the rest of us have to pay it.

PMID- 8876105
TI  - Home ventilation of a child with motor and sensory neuropathy. Central funding
      and a central resource providing information are needed.

PMID- 8876106
TI  - Home ventilation of a child with motor and sensory neuropathy. Study aims to set
      up national database of children receiving ventilatory support.

PMID- 8876107
TI  - GPs need to be more proactive in providing health care to teenagers.

PMID- 8876108
TI  - Survival of patients initially resuscitated from out of hospital cardiac arrest.
      Study did not include patients admitted for intensive care.

PMID- 8876109
TI  - Data on eligibility for thrombolytic treatment cannot be generalised.

PMID- 8876110
TI  - Sunscreens, suntans, and skin cancer. Local councils should remove sunbeds from
      leisure centres.

PMID- 8876111
TI  - Sunscreens, suntans and skin cancer. People do not apply enough sunscreen for
      protection.

PMID- 8876112
TI  - Sunscreens, suntans and skin cancer. Knowledge about sunscreens is inadequate.

PMID- 8876113
TI  - Much effort is spent on treating drug misusers in prison.

PMID- 8876114
TI  - Community leg ulcer clinics. Data were missing from paper.

PMID- 8876115
TI  - Community leg ulcer clinics. Early vascular assessment should be carried out.

PMID- 8876116
TI  - Reference range for potassium concentration is lower in Barbados than Europe.

PMID- 8876117
TI  - Misdiagnosing the persistent vegetative state. Persistent vegetative state should
      not be diagnosed until 12 months from onset of coma.

PMID- 8876118
TI  - Misdiagnosing the persistent vegetative state. Misdiagnosis certainly occurs.

PMID- 8876119
TI  - Young female doctors report achieving fewer surgical skills than young male
      doctors.

PMID- 8876120
TI  - Advertisement for toremifene. Playing on women's fears is unethical.

PMID- 8876121
TI  - Community pharmacists are increasingly supervising treatments.

PMID- 8876122
TI  - Septic arthritis in osteoarthritic hips. Authors' interpretation of radiograph
      was wrong.

PMID- 8876123
TI  - More emergency insulin distribution projects should be set up.

PMID- 8876124
TI  - Stress in general practice. Stressed doctors should take time to recover before
      deciding on their future.

PMID- 8876125
TI  - Stress in general practice. General practitioners must educate patients in the
      appropriate use of services.

PMID- 8876126
TI  - American guidelines on managed care are not the answer.

PMID- 8876127
TI  - Genetic engineering of viruses and of virus vectors: a preface.

PMID- 8876128
TI  - Site-specific integration by adeno-associated virus.
AB  - Adeno-associated virus (AAV) has attracted considerable interest as a potential
      vector for gene delivery. Wild-type virus is notable for the lack of association
      with any human disease and the ability to stably integrate its genome in a site
      specific manner in a locus on human chromosome 19 (AAVS1). Use of a functional
      model system for AAV DNA integration into AAVS1 has allowed us to conclude that
      the recombination event is directed by cellular DNA sequences. Recombinant
      junctions isolated from our integration assay were analyzed and showed
      characteristics similar to those found in latently infected cell lines. The
      minimal DNA signals within AAVS1 required for targeted integration were
      identified and shown to contain functional motifs of the viral origin of
      replication. A replication mediated model of AAV DNA integration is proposed.

PMID- 8876129
TI  - Oncogenic potential of the adenovirus E4orf6 protein.
AB  - The group C adenovirus E4orf6 protein has previously been shown to bind to the
      p53 cellular tumor suppressor protein and block its ability to activate
      transcription. Here we show that the E4orf6 protein blocks the induction of p53
      mediated apoptosis when AT6 cells, which harbor a temperature-sensitive p53, are
      shifted to the permissive temperature. The E4orf6 protein does not, however,
      prevent the induction of apoptosis in p53-deficient H1299 cells by treatment with
      tumor necrosis factor alpha and cycloheximide. The E4orf6 protein also cooperates
      with the adenovirus E1A protein to transform primary baby rat kidney cells, and
      it cooperates with the adenovirus E1A plus E1B 19-kDa and E1B 55-kDa proteins to
      increase the number of baby rat kidney cell transformants and enhance the rate at
      which they arise. The level of p53 is substantially reduced in transformed cells
      expressing the E4orf6 protein in comparison to adenovirus transformants lacking
      it. The E4orf6 gene also accelerates tumor formation when transformed baby rat
      kidney cells are injected subcutaneously into the nude mouse, and it converts
      human 293 cells from nontumorigenic to tumorigenic in nude mice. In addition to
      the well-studied E1A and E1B oncogenes, group C adenoviruses harbor a third
      oncogene, E4orf6, which functions in some respects similarly to the E1B oncogene.

PMID- 8876131
TI  - The function of herpes simplex virus genes: a primer for genetic engineering of
      novel vectors.
AB  - Herpes simplex virus vectors are being developed for delivery and expression of
      human genes to the central nervous system, selective destruction of cancer cells,
      and as carriers for genes encoding antigens that induce protective immunity
      against infectious agents. Vectors constructed to meet these objectives must
      differ from wild-type virus with respect to host range, reactivation from
      latency, and expression of viral genes. The vectors currently being developed are
      (i) helper free amplicons, (ii) replication defective viruses, and (iii)
      genetically engineered replication competent viruses with restricted host range.
      Whereas the former two types of vectors require stable, continuous cell lines
      expressing viral genes for their replication, the replication competent viruses
      will replicate on approved primary human cell strains.

PMID- 8876130
TI  - Adenovirus-mediated interleukin-12 gene therapy for metastatic colon carcinoma.
AB  - Recombinant adenoviral mediated delivery of suicide and cytokine genes has been
      investigated as a treatment for hepatic metastases of colon carcinoma in mice.
      Liver tumors were established by intrahepatic implantation of a poorly
      immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in BALB/c
      mice. Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase
      (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic
      tumor regression, induced an effective systemic antitumoral immunity in the host
      and prolonged the median survival time of the treated animals from 22 to 35 days.
      The antitumoral immunity declined gradually, which led to tumor recurrence over
      time. A recombinant adenovirus expressing the mIL-12 gene was constructed and
      tested in the MCA-26 tumor model. Intratumoral administration of this cytokine
      vector alone increased significantly survival time of the animals with 25% of the
      treated animals still living over 70 days. These data indicate that local
      expression of IL-12 may also be an attractive treatment strategy for metastatic
      colon carcinoma.

PMID- 8876133
TI  - Replication-defective herpes simplex virus vectors for gene transfer in vivo.

PMID- 8876132
TI  - The application of genetically engineered herpes simplex viruses to the treatment
      of experimental brain tumors.
AB  - Due to lack of effective therapy, primary brain tumors are the focus of intense
      investigation of novel experimental approaches that use vectors and recombinant
      viruses. Therapeutic approaches have been both indirect, whereby vectors are
      used, or direct to allow for direct cell killing by the introduced virus.
      Genetically engineered herpes simplex viruses are currently being evaluated as an
      experimental approach to eradicate malignant human gliomas. Initial studies with
      gamma (1)34.5 mutants, R3616 (from which both copies of the gamma (1)34.5 gene
      have been deleted) and R4009 (a construct with two stop codons inserted into the
      gamma (1)34.5 gene), have been assessed. In a syngeneic scid mouse intracranial
      tumor model, recombinant herpes simplex virus can be experimentally used for the
      treatment of brain tumors. These viruses and additional engineered viruses were
      subsequently tested in human glioma cells both in vitro and in vivo. Using a
      xenogeneic scid mouse intracranial glioma model, R4009 therapy of established
      tumors significantly prolonged survival. Most importantly, long-term survival was
      achieved, with histologic evidence that R4009 eradicated intracranial tumors in
      this model. Furthermore, the opportunity to evaluate gamma (1)34.5 mutants that
      have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the
      gamma (1)34.5 gene has been replaced by the murine homologue, MyD116, are
      considered.

PMID- 8876134
TI  - A deletion mutant in the human cytomegalovirus gene encoding IE1(491aa) is
      replication defective due to a failure in autoregulation.
AB  - Human cytomegalovirus (CMV) replication begins with the expression of two
      regulatory proteins, IE1(491aa) and IE2(579aa), produced from differentially
      spliced transcripts under control of the ie1/ie2 promoter-enhancer. A deletion
      mutation removing all 406 IE1(491aa)-specific amino acids was engineered into the
      viral genome and this mutant (RC303 delta Acc) was propagated on an IE1(491aa)
      expressing human fibroblast cell line (ihfie1.3). RC303 delta Acc failed to
      replicate on normal human fibroblasts at low multiplicities of infection (mois).
      At mois > 3 plaque-forming units per cell, virus replication and production of
      progeny were comparable to wild type. However, at mois between 0.01 and 1, mutant
      virus replicated slowly on normal fibroblasts, a pattern that suggested
      initiation of productive infection required multiple hits. Replication of RC303
      delta Acc correlated with the ability to express IE2(579aa), consistent with a
      role for IE1(491aa) in positive autoregulation of the ie1/ie2 promoter-enhancer
      and with data suggesting that virion transactivators compensate for the lack of
      IE1(491aa) under high moi conditions. ie1-deficient CMV should be completely
      avirulent, suggesting its utility as a gene therapy vector for hematopoietic
      progenitors that are normal sites of CMV latency.

PMID- 8876135
TI  - Human cytomegalovirus US3 impairs transport and maturation of major
      histocompatibility complex class I heavy chains.
AB  - The human cytomegalovirus (HCMV) early glycoprotein products of the US11 and US2
      open reading frames cause increased turnover of major histocompatibility complex
      (MHC) class I heavy chains. Since US2 is homologous to another HCMV gene (US3),
      we hypothesized that the US3 gene product also may affect MHC class I expression.
      In cells constitutively expressing the HCMV US3 gene, MHC class I heavy chains
      formed a stable complex with beta 2-microglobulin. However, maturation of the N
      linked glycan of MHC class I heavy chains was impaired in US3+ cells. The
      glycoprotein product of US3 (gpUS3) occurs mostly in a high-mannose form and
      coimmunoprecipitates with beta 2-microglobulin associated class I heavy chains.
      Mature class I molecules were detected at steady state on the surface of US3+
      cells, as in control cells. Substantial perinuclear accumulation of heavy chains
      was observed in US3+ cells. The data suggest that gpUS3 impairs egress of MHC
      class I heavy chains from the endoplasmic reticulum.

PMID- 8876136
TI  - Epstein-Barr virus vectors for gene delivery to B lymphocytes.
AB  - Basic research in Epstein-Barr virus (EBV) molecular genetics has provided means
      to maintain episomes in human cells, to efficiently deliver episomes with up to
      150 kbp of heterologous DNA to human B lymphocytes, and to immortalize human B
      lymphocytes with EBV recombinants that can maintain up to 120 kbp of heterologous
      DNA. Episome maintenance requires an EBV nuclear protein, EBNA1, whereas
      immortalization of cells with EBV recombinants requires EBNA1, EBNA2, EBNA3A,
      EBNA3C, EBNALP, and LMP1. EBV-derived vectors are useful for experimental genetic
      reconstitution in B lymphocytes, a cell type frequently used in establishing
      repositories of human genetic deficiencies. The ability of EBV-infected cells to
      establish a balanced state of persistence in normal humans raises the possibility
      that cells infected with EBV recombinants could be useful for genetic
      reconstitution, in vivo.

PMID- 8876138
TI  - Applications of pox virus vectors to vaccination: an update.
AB  - Recombinant pox viruses have been generated for vaccination against heterologous
      pathogens. Amongst these, the following are notable examples. (i) The engineering
      of the Copenhagen strain of vaccinia virus to express the rabies virus
      glycoprotein. When applied in baits, this recombinant has been shown to vaccinate
      the red fox in Europe and raccoons in the United States, stemming the spread of
      rabies virus infection in the wild. (ii) A fowlpox-based recombinant expressing
      the Newcastle disease virus fusion and hemagglutinin glycoproteins has been shown
      to protect commercial broiler chickens for their lifetime when the vaccine was
      administered at 1 day of age, even in the presence of maternal immunity against
      either the Newcastle disease virus or the pox vector. (iii) Recombinants of
      canarypox virus, which is restricted for replication to avian species, have
      provided protection against rabies virus challenge in cats and dogs, against
      canine distemper virus, feline leukemia virus, and equine influenza virus
      disease. In humans, canarypox virus-based recombinants expressing antigens from
      rabies virus, Japanese encephalitis virus, and HIV have been shown to be safe and
      immunogenic. (iv) A highly attenuated vaccinia derivative, NYVAC, has been
      engineered to express antigens from both animal and human pathogens. Safety and
      immunogenicity of NYVAC-based recombinants expressing the rabies virus
      glycoprotein, a polyprotein from Japanese encephalitis virus, and seven antigens
      from Plasmodium falciparum have been demonstrated to be safe and immunogenic in
      early human vaccine studies.

PMID- 8876137
TI  - Genetically engineered poxviruses for recombinant gene expression, vaccination,
      and safety.
AB  - Vaccinia virus, no longer required for immunization against smallpox, now serves
      as a unique vector for expressing genes within the cytoplasm of mammalian cells.
      As a research tool, recombinant vaccinia viruses are used to synthesize and
      analyze the structure-function relationships of proteins, determine the targets
      of humoral and cell-mediated immunity, and investigate the types of immune
      response needed for protection against specific infectious diseases and cancer.
      The vaccine potential of recombinant vaccinia virus has been realized in the form
      of an effective oral wild-life rabies vaccine, although no product for humans has
      been licensed. A genetically altered vaccinia virus that is unable to replicate
      in mammalian cells and produces diminished cytopathic effects retains the
      capacity for high-level gene expression and immunogenicity while promising
      exceptional safety for laboratory workers and potential vaccine recipients.

PMID- 8876139
TI  - Negative-strand RNA viruses: genetic engineering and applications.
AB  - The negative-strand RNA viruses are a broad group of animal viruses that comprise
      several important human pathogens, including influenza, measles, mumps, rabies,
      respiratory syncytial, Ebola, and hantaviruses. The development of new strategies
      to genetically manipulate the genomes of negative-strand RNA viruses has provided
      us with new tools to study the structure-function relationships of the viral
      components and their contributions to the pathogenicity of these viruses. It is
      also now possible to envision rational approaches--based on genetic engineering
      techniques--to design live attenuated vaccines against some of these viral
      agents. In addition, the use of different negative-strand RNA viruses as vectors
      to efficiently express foreign polypeptides has also become feasible, and these
      novel vectors have potential applications in disease prevention as well as in
      gene therapy.

PMID- 8876140
TI  - Foreign glycoproteins expressed from recombinant vesicular stomatitis viruses are
      incorporated efficiently into virus particles.
AB  - In a previous study we demonstrated that vesicular stomatitis virus (VSV) can be
      used as a vector to express a soluble protein in mammalian cells. Here we have
      generated VSV recombinants that express four different membrane proteins: the
      cellular CD4 protein, a CD4-G hybrid protein containing the ectodomain of CD4 and
      the transmembrane and cytoplasmic tail of the VSV glycoprotein (G), the measles
      virus hemagglutinin, or the measles virus fusion protein. The proteins were
      expressed at levels ranging from 23-62% that of VSV G protein and all were
      transported to the cell surface. In addition we found that all four proteins were
      incorporated into the membrane envelope of VSV along with the VSV G protein. The
      levels of incorporation of these proteins varied from 6-31% of that observed for
      VSV G. These results suggest that many different membrane proteins may be co
      incorporated quite efficiently with VSV G protein into budding VSV virus
      particles and that specific signals are not required for this co-incorporation
      process. In fact, the CD4-G protein was incorporated with the same efficiency as
      wild type CD4. Electron microscopy of virions containing CD4 revealed that the
      CD4 molecules were dispersed throughout the virion envelope among the trimeric
      viral spike glycoproteins. The recombinant VSV-CD4 virus particles were about 18%
      longer than wild type virions, reflecting the additional length of the helical
      nucleocapsid containing the extra gene. Recombinant VSVs carrying foreign
      antigens on the surface of the virus particle may be useful for viral targeting,
      membrane protein purification, and for generation of immune responses.

PMID- 8876141
TI  - Specific infection of CD4+ target cells by recombinant rabies virus pseudotypes
      carrying the HIV-1 envelope spike protein.
AB  - A recombinant rabies virus (RV) mutant deficient for the surface spike
      glycoprotein (G) gene was used to study the incorporation of envelope proteins
      from HIV-1 expressed from transfected plasmids. A hybrid HIV-1 protein in which
      the cytoplasmic domain was replaced with that of RV G was incorporated into the
      virus envelope and rescued the infectivity of the RV mutant. The RV(HIV-1)
      pseudotype viruses could infect only CD4+ cells, and their infectivity was
      neutralized specifically by anti-HIV-1 sera. In contrast to the chimeric protein,
      wild-type HIV-1 envelope protein or mutants with truncated cytoplasmic domains
      failed to produce pseudotyped particles. This indicates the presence of a
      specific signal in the RV G cytoplasmic domain, allowing correct incorporation of
      a spike protein into the envelope of rhabdovirus particles. The possibility of
      directing the cell tropism of RV by replacement of the RV G with proteins of
      defined receptor specificity should prove useful for future development of
      targetable gene delivery vectors.

PMID- 8876142
TI  - Alphavirus-based expression vectors: strategies and applications.
AB  - Alphaviruses are positive-strand RNA viruses that can mediate efficient
      cytoplasmic gene expression in insect and vertebrate cells. Through recombinant
      DNA technology, the alphavirus RNA replication machinery has been engineered for
      high-level expression of heterologous RNAs and proteins. Amplification of
      replication-competent alpha-virus RNAs (replicons) can be initiated by RNA or DNA
      transfection and a variety of packaging systems have been developed for producing
      high titers of infectious viral particles. Although normally cytocidal for
      vertebrate cells, variants with adaptive mutations allowing noncytopathic
      replication have been isolated from persistently infected cultures or selected
      using a dominant selectable marker. Such mutations have been mapped and used to
      create new alphavirus vectors for noncytopathic gene expression in mammalian
      cells. These vectors allow long-term expression at moderate levels and complement
      previous vectors designed for short-term high-level expression. Besides their use
      for a growing number of basic research applications, recombinant alphavirus RNA
      replicons may also facilitate genetic vaccination and transient gene therapy.

PMID- 8876143
TI  - Early events in poliovirus infection: virus-receptor interactions.
AB  - The interaction of poliovirus with its cell receptor initiates conformational
      changes that lead to uncoating of the viral RNA. Three types of genetic analyses
      have been used to study the poliovirus-receptor interaction: (i) mutagenesis of
      the poliovirus receptor (PVR), (ii) selection of viral mutants resistant to
      neutralization with soluble PVR, and (iii) selection of viral variants adapted to
      use mutant PVRs. The results of these studies show that a small portion of the
      first immunoglobulin-like domain of PVR contacts viral residues within a deep
      depression on the surface of the capsid that encircles the fivefold axis of
      symmetry. Viral capsid residues that influence the interaction with PVR are also
      found in locations such as the capsid interior that cannot directly contact PVR.
      These mutations might influence the ability of the capsid to undergo receptor
      mediated conformational transitions that are necessary for high-affinity
      interactions with PVR.

PMID- 8876144
TI  - Efficient transfer, integration, and sustained long-term expression of the
      transgene in adult rat brains injected with a lentiviral vector.
AB  - We describe the construction of a safe, replication-defective and efficient
      lentiviral vector suitable for in vivo gene delivery. The reverse transcription
      of the vector was found to be a rate-limiting step; therefore, promoting the
      reaction inside the vector particles before delivery significantly enhanced the
      efficiency of gene transfer. After injection into the brain of adult rats,
      sustained long-term expression of the transgene was obtained in the absence of
      detectable pathology. A high proportion of the neurons in the areas surrounding
      the injection sites of the vector expressed the transduced beta-galactosidase
      gene. This pattern was invariant in animals sacrificed several months after a
      single administration of the vector. Transduction occurs by integration of the
      vector genome, as it was abolished by a single amino acid substitution in the
      catalytic site of the integrase protein incorporated in the vector. Development
      of clinically acceptable derivatives of the lentiviral vector may thus enable the
      sustained delivery of significant amounts of a therapeutic gene product in a wide
      variety of somatic tissues.

PMID- 8876145
TI  - Use of virion DNA as a cloning vector for the construction of mutant and
      recombinant herpesviruses.
AB  - We have developed improved procedures for the isolation of deletion mutant, point
      mutant, and recombinant herpesvirus saimiri. These procedures take advantage of
      the absence of NotI and AscI restriction enzyme sites within the viral genome and
      use reporter genes for the identification of recombinant viruses. Genes for
      secreted engineered alkaline phosphatase and green fluorescent protein were
      placed under simian virus 40 early promoter control and flanked by NotI and AscI
      restriction sites. When permissive cells were cotransfected with herpesvirus
      saimiri virion DNA and one of the engineered reporter genes cloned within
      herpesvirus saimiri sequences, recombinant viruses were readily identified and
      purified on the basis of expression of the reporter gene. Digestion of
      recombinant virion DNA with NotI or AscI was used to delete the reporter gene
      from the recombinant herpesvirus saimiri. Replacement of the reporter gene can be
      achieved by NotI or AscI digestion of virion DNA and ligation with a terminally
      matched fragment or, alternatively, by homologous recombination in cotransfected
      cells. Any gene can, in theory, be cloned directly into the virion DNA when
      flanked by the appropriate NotI or AscI sites. These procedures should be widely
      applicable in their general form to most or all herpesviruses that replicate
      permissively in cultured cells.

PMID- 8876146
TI  - Development of HIV vectors for anti-HIV gene therapy.
AB  - Current gene therapy protocols for HIV infection use transfection or murine
      retrovirus mediated transfer of antiviral genes into CD4+ T cells or CD34+
      progenitor cells ex vivo, followed by infusion of the gene altered cells into
      autologous or syngeneic/allogeneic recipients. While these studies are essential
      for safety and feasibility testing, several limitations remain: long-term
      reconstitution of the immune system is not effected for lack of access to the
      macrophage reservoir or the pluripotent stem cell population, which is usually
      quiescent, and ex vivo manipulation of the target cells will be too expensive and
      impractical for global application. In these regards, the lentivirus-specific
      biologic properties of the HIVs, which underlie their pathogenetic mechanisms,
      are also advantageous as vectors for gene therapy. The ability of HIV to
      specifically target CD4+ cells, as well as non-cycling cells, makes it a
      promising candidate for in vivo gene transfer vector on one hand, and for
      transduction of non-cycling stem cells on the other. Here we report the use of
      replication-defective vectors and stable vector packaging cell lines derived from
      both HIV-1 and HIV-2. Both HIV envelopes and vesicular stomatitis virus
      glycoprotein G were effective in mediating high-titer gene transfer, and an HIV-2
      vector could be cross-packaged by HIV-1. Both HIV-1 and HIV-2 vectors were able
      to transduce primary human macrophages, a property not shared by murine
      retroviruses. Vesicular stomatitis virus glycoprotein G-pseudotyped HIV vectors
      have the potential to mediate gene transfer into non-cycling hematopoietic stem
      cells. If so, HIV or other lentivirus-based vectors will have applications beyond
      HIV infection.

PMID- 8876147
TI  - A stable human-derived packaging cell line for production of high titer
      retrovirus/vesicular stomatitis virus G pseudotypes.
AB  - We have generated a human 293-derived retroviral packaging cell line (293GPG)
      capable of producing high titers of recombinant Moloney murine leukemia virus
      particles that have incorporated the vesicular stomatitis virus G (VSV-G)
      protein. To achieve expression of the retroviral gag-pol polyprotein, the precise
      coding sequences for gag-pol were introduced into a vector which utilizes totally
      nonretroviral signals for gene expression. Because constitutive expression of the
      VSV-G protein is toxic in 293 cells, we used the tetR/VP 16 transactivator and
      teto minimal promoter system for inducible, tetracycline-regulatable expression
      of VSV-G. After stable transfection of the 293GPG packaging cell line with the
      MFG.SnlsLacZ retroviral vector construct, it was possible to readily isolate
      stable virus-producing cell lines with titers approaching 10(7) colony-forming
      units/ml. Transient transfection of 293GPG cells using a modified version of
      MFG.SnlsLacZ, in which the cytomegalovirus IE promoter was used to drive
      transcription of the proviral genome, led to titers of approximately 10(6) colony
      forming units/ml. The retroviral/VSV-G pseudotypes generated using 293GPG cells
      were significantly more resistant to human complement than commonly used
      amphotropic vectors and could be highly concentrated (> 1000-fold). This new
      packaging cell line may prove to be particularly useful for assessing the
      potential use of retroviral vectors for direct in vivo gene transfer. The design
      of the cell line also provides at least theoretical advantages over existing cell
      lines with regard to the possible release of replication-competent virus.

PMID- 8876148
TI  - Cell-surface receptors for retroviruses and implications for gene transfer.
AB  - Retroviruses can utilize a variety of cell-surface proteins for binding and entry
      into cells, and the cloning of several of these viral receptors has allowed
      refinement of models to explain retrovirus tropism. A single receptor appears to
      be necessary and sufficient for entry of many retroviruses, but exceptions to
      this simple model are accumulating. For example, HIV requires two proteins for
      cell entry, neither of which alone is sufficient; 10A1 murine leukemia virus can
      enter cells by using either of two distinct receptors; two retroviruses can use
      different receptors in some cells but use the same receptor for entry into other
      cells; and posttranslational protein modifications and secreted factors can
      dramatically influence virus entry. These findings greatly complicate the rules
      governing retrovirus tropism. The mechanism underlying retrovirus evolution to
      use many receptors for cell entry is not clear, although some evidence supports a
      mutational model for the evolution of new receptor specificities. Further study
      of factors that govern retrovirus entry into cells are important for achieving
      high-efficiency gene transduction to specific cells and for the design of
      retroviral vectors to target additional receptors for cell entry.

PMID- 8876149
TI  - Immunization with DNA vaccines encoding glycoprotein D or glycoprotein B, alone
      or in combination, induces protective immunity in animal models of herpes simplex
      virus-2 disease.
AB  - DNA vaccines expressing herpes simplex virus type 2 (HSV-2) full-length
      glycoprotein D (gD), or a truncated form of HSV-2 glycoprotein B (gB) were
      evaluated for protective efficacy in two experimental models of HSV-2 infection.
      Intramuscular (i.m.) injection of mice showed that each construction induced
      neutralizing serum antibodies and protected the mice from lethal HSV-2 infection.
      Dose-titration studies showed that low doses (< or = 1 microgram) of either DNA
      construction induced protective immunity, and that a single immunization with the
      gD construction was effective. The two DNAs were then tested in a low-dosage
      combination in guinea pigs. Immune sera from DNA-injected animals had antibodies
      to both gD and gB, and virus neutralizing activity. When challenged by vaginal
      infection with HSV-2, the DNA-immunized animals were significantly protected from
      primary genital disease.

PMID- 8876150
TI  - Fusigenic viral liposome for gene therapy in cardiovascular diseases.
AB  - To improve the efficiency of liposome-mediated DNA transfer as a tool for gene
      therapy, we have developed a fusigenic liposome vector based on principles of
      viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ;
      also Sendai virus) are complexed with liposomes that encapsulate
      oligodeoxynucleotide or plasmid DNA. Subsequent fusion of HVJ-liposomes with
      plasma membranes introduces the DNA directly into the cytoplasm. In addition, a
      DNA-binding nuclear protein is incorporated into the HVJ-liposome particle to
      enhance plasmid transgene expression. The fusigenic viral liposome vector has
      proven to be efficient for the intracellular introduction of
      oligodeoxynucleotide, as well as intact genes up to 100 kbp, both in vitro and in
      vivo. Many animal tissues have been found to be suitable targets for fusigenic
      viral liposome DNA transfer. In the cardiovascular system, we have documented
      successful cytostatic gene therapy in models of vascular proliferative disease
      using antisense oligodeoxynucleotides against cell cycle genes, double-stranded
      oligodeoxynucleotides as "decoys" to trap the transcription factor E2F, and
      expression of a transgene encoding the constitutive endothelial cell form of
      nitric oxide synthase. Similar strategies are also effective for the genetic
      engineering of vein grafts and for the treatment of a mouse model of immune
      mediated glomerular disease.

PMID- 8876151
TI  - A speed limit for protein folding.

PMID- 8876152
TI  - On the failure of de novo-designed peptides as biocatalysts.
AB  - While the elegance and efficiency of enzymatic catalysis have long tempted
      chemists and biochemists with reductionist leanings to try to mimic the functions
      of natural enzymes in much smaller peptides, such efforts have only rarely
      produced catalysts with biologically interesting properties. However, the advent
      of genetic engineering and hybridoma technology and the discovery of catalytic
      RNA have led to new and very promising alternative means of biocatalyst
      development. Synthetic chemists have also had some success in creating nonpeptide
      catalysts with certain enzyme-like characteristics, although their rates and
      specificities are generally much poorer than those exhibited by the best novel
      biocatalysts based on natural structures. A comparison of the various approaches
      from theoretical and practical viewpoints is presented. It is suggested that,
      given our current level of understanding, the most fruitful methods may
      incorporate both iterative selection strategies and rationally chosen small
      perturbations, superimposed on frameworks designed by nature.

PMID- 8876153
TI  - Mirror symmetry breaking at the molecular level.
AB  - Reasoning from two basic principles of molecular physics, P invariance of
      electromagnetic interaction and the second law of thermodynamics, one would
      conclude that mirror symmetry retained in the world of chiral molecules. This
      inference is fully consistent with what is observed in inorganic nature. However,
      in the bioorganic world, the reverse is true. Mirror symmetry there is definitely
      broken. Is it possible to account for this phenomenon without going beyond
      conventional concepts of the kinetics of enantioselective processes? This study
      is an attempt to survey all existing hypotheses containing this phenomenon.

PMID- 8876154
TI  - Rapid preparation of giant unilamellar vesicles.
AB  - We report here a rapid evaporation method that produces in high yield giant
      unilamellar vesicles up to 50 microns in diameter. The vesicles are obtained
      after only 2 min and can be prepared from different phospholipids, including L
      alpha-phosphatidylcholine (lecithin), dipalmitoleoyl L-alpha-phosphatidylcholine,
      and beta-arachidonoyl gamma-palmitoyl L-alpha-phosphatidylcholine. Vesicles can
      be produced in distilled water and in Hepes, phosphate, and borate buffers in the
      pH range of 7.0 to 11.5 with ionic strengths up to 50 mM. The short preparation
      time allows encapsulation of labile molecular targets or enzymes with high
      catalytic activities. Cell-sized proteoliposomes have been prepared in which
      gamma-glutamyltransferase (EC 2.3.2.2) was functionally incorporated into the
      membrane wall.

PMID- 8876155
TI  - Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits
      prevents diet-induced atherosclerosis.
AB  - Lecithin:cholesterol acyltransferase (LCAT) is a key plasma enzyme in cholesterol
      and high density lipoprotein (HDL) metabolism. Transgenic rabbits overexpressing
      human LCAT had 15-fold greater plasma LCAT activity that nontransgenic control
      rabbits. This degree of overexpression was associated with a 6.7-fold increase in
      the plasma HDL cholesterol concentration in LCAT transgenic rabbits. On a 0.3%
      cholesterol diet, the HDL cholesterol concentrations increased from 24 +/- 1 to
      39 +/- 3 mg/dl in nontransgenic control rabbits (n = 10; P < 0.05) and increased
      from 161 +/- 5 to 200 +/- 21 mg/dl (P < 0.001) in the LCAT transgenic rabbits (n
      = 9). Although the baseline non-HDL concentrations of control (4 +/- 3 mg/dl) and
      transgenic rabbits (18 +/- 4 mg/dl) were similar, the cholesterol-rich diet
      raised the non-HDL cholesterol concentrations, reflecting the atherogenic very
      low density, intermediate density, and low density lipoprotein particles observed
      by gel filtration chromatography. The non-HDL cholesterol rose to 509 +/- 57
      mg/dl in controls compared with only 196 +/- 14 mg/dl in the LCAT transgenic
      rabbits (P < 0.005). The differences in the plasma lipoprotein response to a
      cholesterol-rich diet observed in the transgenic rabbits paralleled the
      susceptibility to developing aortic atherosclerosis. Compared with nontransgenic
      controls, LCAT transgenic rabbits were protected from diet-induced
      atherosclerosis with significant reductions determined by both quantitative
      planimetry (-86%; P < 0.003) and quantitative immunohistochemistry (-93%; P <
      0.009). Our results establish the importance of LCAT in the metabolism of both
      HDL and apolipoprotein B-containing lipoprotein particles with cholesterol
      feeding and the response to diet-induced atherosclerosis. In addition, these
      findings identify LCAT as a new target for therapy to prevent atherosclerosis.

PMID- 8876157
TI  - Whole body nitric oxide synthesis in healthy men determined from [15N] arginine
      to-[15N]citrulline labeling.
AB  - The rates of whole body nitric oxide (NO) synthesis, plasma arginine flux, and de
      novo arginine synthesis and their relationships to urea production, were examined
      in a total of seven healthy adults receiving an L-amino acid diet for 6 days. NO
      synthesis was estimated by the rate of conversion of the [15N] guanidino nitrogen
      of arginine to plasma [15N] ureido citrulline and compared with that based on
      urinary nitrite (NO2-)/nitrate (NO3-) excretion. Six subjects received on dietary
      day 7, a 24-hr (12-hr fed/12-hr fasted) primed, constant, intravenous infusion of
      L-[guanidino-15N2]arginine and [13C]urea. A similar investigation was repeated
      with three of these subjects, plus an additional subject, in which they received
      L-[ureido-13C]citrulline, to determine plasma citrulline fluxes. The estimated
      rates (mean +/- SD) of NO synthesis over a period of 24 hr averaged 0.96 +/- 0.1
      mumol .kg-1.hr-1 and 0.95 +/- 0.1 mumol.kg-1.hr-1, for the [15N]citrulline and
      the nitrite/nitrate methods, respectively. About 15% of the plasma arginine
      turnover was associated with urea formation and 1.2% with NO formation. De novo
      arginine synthesis averaged 9.2 +/- 1.4 mumol. kg-1.hr-1, indicating that
      approximately 11% of the plasma arginine flux originates via conversion of plasma
      citrulline to arginine. Thus, the fraction of the plasma arginine flux associated
      with NO and also urea synthesis in healthy humans is small, although the plasma
      arginine compartment serves as a significant precursor pool (54%) for whole body
      NO formation. This tracer model should be useful for exploring these metabolic
      relationships in vivo, under specific pathophysiologic states where the L
      arginine-NO pathway might be altered.

PMID- 8876156
TI  - A novel cationic lipid greatly enhances plasmid DNA delivery and expression in
      mouse lung.
AB  - Effective gene therapy for lung tissue requires the use of efficient vehicles to
      deliver the gene of interest into lung cells. When plasmid DNA encoding
      chloramphenicol acetyltransferase (CAT) was administered intranasally to BALB/c
      mice without carrier lipids, CAT activity was detected in mouse lung extracts.
      Plasmid DNA delivered with optimally formulated commercially available
      transfection reagents expressed up to 10-fold more CAT activity in lung than
      observed with naked DNA alone. Liposome formulations consisting of (+/-)-N-(3
      aminopropyl)-N,N-dimethyl-2,3-bis (dodecyloxy)-1-propanaminium bromide (GAP
      DLRIE) plus the neutral colipid dioleoylphosphatidylethanolamine (DOPE) enhanced
      CAT expression by more than 100-fold relative to plasmid DNA alone. A single
      administration of GAP-DLRIE liposome-CAT DNA complexes to mouse lung elicited
      peak expression at days 1-4 posttransfection, followed by a gradual return to
      baseline by day 21 postadministration. Readministration of GAP-DLRIE liposome CAT
      complexes at day 21 led to another transient peak of reporter gene expression.
      Histological examination of lungs treated with GAP-DLRIE complexed beta
      galactosidase DNA revealed that alveolar epithelial cells were the primary locus
      of expression and that up to 1% of all alveoli contained epithelial cells
      expressing the transgene.

PMID- 8876158
TI  - Cloning of human acetyl-CoA carboxylase-beta and its unique features.
AB  - Acetyl-CoA carboxylase, which has a molecular mass of 265 kDa (ACC-alpha),
      catalyzes the rate-limiting step in the biosynthesis of long-chain fatty acids.
      In this study we report the complete amino acid sequence and unique features of
      an isoform of ACC with a molecular mass of 275 kDa (ACC-beta), which is primarily
      expressed in heart and skeletal muscles. In these tissues, ACC-beta may be
      involved in the regulation of fatty acid oxidation, rather than fatty acid
      biosynthesis. ACC-beta contains an amino acid sequence at the N terminus which is
      about 200 amino acids long and may be uniquely related to the role of ACC-beta in
      controlling carnitine palmitoyltransferase I activity and fatty acid oxidation by
      mitochondria. If we exclude this unique sequence at the N terminus the two forms
      of ACC show about 75% amino acid identity. All of the known functional domains of
      ACC are found in the homologous regions. Human ACC-beta cDNA has an open reading
      frame of 7,343 bases, encoding a protein of 2,458 amino acids, with a calculated
      molecular mass of 276,638 Da. The mRNA size of human ACC-beta is approximately 10
      kb and is primarily expressed in heart and skeletal muscle tissues, whereas ACC
      alpha mRNA is detected in all tissues tested. A fragment of ACC-beta cDNA was
      expressed in Escherichia coli and antibodies against the peptide were generated
      to establish that the cDNA sequence that we cloned is that for ACC-beta.

PMID- 8876159
TI  - Association of RNase mitochondrial RNA processing enzyme with ribonuclease P in
      higher ordered structures in the nucleolus: a possible coordinate role in
      ribosome biogenesis.
AB  - RNase mitochondrial RNA processing enzyme (MRP) is a nucleolar ribonucleoprotein
      particle that participates in 5.8S ribosomal RNA maturation in eukaryotes. This
      enzyme shares a polypeptide and an RNA structural motif with ribonuclease P
      (RNase P), a nuclear endoribonuclease originally described in the nucleus that
      processes RNA transcripts to generate their mature 5' termini. Both enzymes are
      also located in mitochondria. This report further characterizes the relationship
      between RNase MRP and RNase P. Antisense affinity selection with biotinylated 2'
      O-methyl oligoribonucleotides and glycerol gradient fractionation experiments
      demonstrated that small subpopulations of RNase MRP and RNase P associate with
      each other in vivo in macromolecular complex, possibly 60-80S preribosomes. This
      latter notion was supported by fluorescence in situ hybridization experiments
      with antisense oligonucleotides that localized that RNA components of RNase MRP
      and RNase P to the nucleolus and to discrete cytoplasmic structures. These
      findings suggest that small subpopulations of RNase MRP and RNase P are
      physically associated, and that both may function in ribosomal RNA maturation or
      ribosome assembly.

PMID- 8876160
TI  - Engineering human immunodeficiency virus 1 protease heterodimers as
      macromolecular inhibitors of viral maturation.
AB  - Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers
      is an essential prerequisite for viral proteolytic activity and the subsequent
      generation of infectious virus particles. Disruption of the dimer interface
      inhibits this activity as does formation of heterodimers between wild-type and
      defective monomers. A structure-based approach was used to identify amino acid
      substitutions at the dimer interface of HIV-1 PR that facilitate preferential
      association of heterodimers and inhibit self-association of the defective
      monomers. Expression of the designed PR monomers inhibits activity of wild-type
      HIV-1 PR and viral infectivity when assayed in an ex vivo model system. These
      results show that it is possible to design PR monomers as macromolecular
      inhibitors that may provide an alternative to small molecule inhibitors for the
      treatment of HIV infection.

PMID- 8876161
TI  - Structure and function in rhodopsin: expression of functional mammalian opsin in
      Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae has been investigated for expression of
      mammalian opsin as an alternative to the currently used expression in COS-1
      mammalian cells. The synthetic opsin gene was placed under the control of the
      inducible promoter GAL1 in the multicopy yeast/ Escherichia coli shuttle vector
      YEpRF1. Transformation of a GAL+ S. cerevisiae strain with the vector and growth
      of galactose-induced cultures to saturation showed the production of 2.0 +/- 0.5
      mg of opsin from about 10(10) cells by ELISA. The addition of 11-cis-retinal to
      either cell spheroplasts or lysed cells showed that a fraction (2-4%) of the
      total expressed opsin reconstituted to rhodopsin. This fraction was purified to
      homogeneity and was shown to be fully functional and indistinguishable from
      bovine rhodopsin by the following criteria: (i) UV-visible absorption spectra,
      (ii) the formation of metarhodopsin II and its rate of decay, and (iii) initial
      rate of transducin activation as measured by the formation of a complex between
      transducin (alpha subunit) and guanosine 5'-[gamma-[35S]thio]triphosphate. The
      purified fraction was homogeneously glycosylated. However, glycosylation was
      distinct from that of bovine rhodopsin as judged by mobility on SDS/PAGE and
      endoglycosidase H sensitivity.

PMID- 8876162
TI  - Structure and function in rhodopsin: high level expression of a synthetic bovine
      opsin gene and its mutants in stable mammalian cell lines.
AB  - Stable mammalian cell lines harboring a synthetic bovine opsin gene have been
      derived from the suspension-adapted HEK293 cell line. The opsin gene is under the
      control of the immediate-early cytomegalovirus promoter/enhancer in an expression
      vector that also contains a selectable marker (Neo) governed by a relatively weak
      promoter. The cell lines expressing the opsin gene at high levels are selected by
      growth in the presence of high concentrations of the antibiotic geneticin. Under
      the conditions used for cell growth in suspension, opsin is produced at saturated
      culture levels of more than 2 mg/liter. After reconstitution with 11-cis-retinal,
      rhodopsin is purified to homogeneity in a single step by immunoaffinity column
      chromatography. Rhodopsin thus prepared (> 90% recovery at concentrations of up
      to 15 microM) is indistinguishable from rhodopsin purified from bovine rod outer
      segments by the following criteria: (i) UV/Vis absorption spectra in the dark and
      after photobleaching and the rate of metarhodopsin II decay, (ii) initial rates
      of transducin activation, and (iii) the rate of phosphorylation by rhodopsin
      kinase. Although mammalian cell opsin migrates slower than rod outer segment
      opsin on SDS/polyacrylamide gels, presumably due to a different N-glycosylation
      pattern, their mobilities after deglycosylation are identical. This method has
      enabled the preparation of several site-specific mutants of bovine opsin in
      comparable amounts.

PMID- 8876163
TI  - Mechanism of oligonucleotide release from cationic liposomes.
AB  - We propose a mechanism for oligonucleotide (ODN) release from cationic lipid
      complexes in cells that accounts for various observations on cationic lipid
      nucleic acid-cell interactions. Fluorescent confocal microscopy of cells treated
      with rhodamine-labeled cationic liposome/ fluorescein-labeled ODN (F-ODN)
      complexes show the F-ODN separates from the lipid after internalization and
      enters the nucleus leaving the fluorescent lipid in cytoplasmic structures. ODN
      displacement from the complex was studied by fluorescent resonance energy
      transfer. Anionic liposome compositions (e.g., phosphatidylserine) that mimic the
      cytoplasmic facing monolayer of the cell membrane released ODN from the complex
      at about a 1:1 (-/+) charge ratio. Release was independent of ionic strength and
      pH. Physical separation of the F-ODN from monovalent and multivalent cationic
      lipids was confirmed by gel electrophoresis. Fluid but not solid phase anionic
      liposomes are required, whereas the physical state of the cationic lipids does
      not effect the release. Water soluble molecules with a high negative linear
      charge density, dextran sulfate, or heparin also release ODN. However, ATP,
      spermidine, spermine, tRNA, DNA, polyglutamic acid, polylysine, bovine serum
      albumin, or histone did not release ODN, even at 100-fold charge excess (-/+).
      Based upon these results, we propose that the complex, after internalization by
      endocytosis, induces flip-flop of anionic lipids from the cytoplasmic facing
      monolayer. Anionic lipids laterally diffuse into the complex and form a charged
      neutralized ion-pair with the cationic lipids. This leads to displacement of the
      ODN from the cationic lipid and its release into the cytoplasm.

PMID- 8876164
TI  - Nitric oxide production in SJL mice bearing the RcsX lymphoma: a model for in
      vivo toxicological evaluation of NO.
AB  - SJL mice spontaneously develop pre-B-cell lymphoma that we hypothesized might
      stimulate macrophages to produce nitric oxide (NO.). Transplantation of an
      aggressive lymphoma (RcsX) was used to induce tumor formation. Urinary nitrate
      excretion was measured as an index of NO. production and was found to increase 50
      fold by 13 days after tumor injection. NO. production was prevented by the
      addition of a nitric oxide synthase (NOS) inhibitor. The expression of inducible
      NOS (iNOS) in various tissues was estimated by Western blot analysis and
      localized by immunohistochemistry. The synthase was detected in the spleen, lymph
      nodes, and liver of treated but not control mice. To assess whether the iNOS
      staining cells were macrophages, spleen sections from ResX-bearing animals were
      costained with anti-iNOS antibody and the anti-macrophage antibody moma-2.
      Expression of iNOS was found to be limited to a subset of the macrophage
      population. The concentration of gamma-interferon, a cytokine known to induce NO.
      production by macrophages, in the serum of tumor-bearing mice, was measured and
      found to be elevated 25-fold above untreated mice. The ability of ResX-activated
      macrophages to inhibit splenocyte growth in primary culture was estimated and
      macrophage-derived NO. was found to inhibit cell division 10-fold. Our findings
      demonstrate that ResX cells stimulate NO. production by macrophages in the spleen
      and lymph nodes of SJL mice, and we believe this experimental model will prove
      useful for study of the toxicological effects of NO. under physiological
      conditions.

PMID- 8876165
TI  - Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state:
      conformational disorder mediates binding diversity.
AB  - The cyclin-dependent kinase (Cdk) inhibitor p21Waf1/Cip1/Sdi1, important for p53
      dependent cell cycle control, mediates G1/S arrest through inhibition of Cdks and
      possibly through inhibition of DNA replication. Cdk inhibition requires a
      sequence of approximately 60 amino acids within the p21 NH2 terminus. We show,
      using proteolytic mapping, circular dichroism spectropolarimetry, and nuclear
      magnetic resonance spectroscopy, that p21 and NH2-terminal fragments that are
      active as Cdk inhibitors lack stable secondary or tertiary structure in the free
      solution state. In sharp contrast to the disordered free state, however, the p21
      NH2 terminus adopts an ordered stable conformation when bound to Cdk2, as shown
      directly by NMR spectroscopy. We have, thus, identified a striking disorder-order
      transition for p21 upon binding to one of its biological targets, Cdk2. This
      structural transition has profound implications in light of the ability of p21 to
      bind and inhibit a diverse family of cyclin-Cdk complexes, including cyclin A
      Cdk2, cyclin E-Cdk2, and cyclin D-Cdk4. Our findings suggest that the
      flexibility, or disorder, of free p21 is associated with binding diversity and
      offer insights into the role for structural disorder in mediating binding
      specificity in biological systems. Further, these observations challenge the
      generally accepted view of proteins that stable secondary and tertiary structure
      are prerequisites for biological activity and suggest that a broader view of
      protein structure should be considered in the context of structure-activity
      relationships.

PMID- 8876166
TI  - Increased histone H1 phosphorylation and relaxed chromatin structure in Rb
      deficient fibroblasts.
AB  - Fibroblasts derived from embryos homozygous for a disruption of the
      retinoblastoma gene (Rb) exhibit a shorter G1 than their wild-type counterparts,
      apparently due to highly elevated levels of cyclin E protein and deregulated
      cyclin-dependent kinase 2 (CDK2) activity. Here we demonstrate that the Rb-/-
      fibroblasts display higher levels of phosphorylated H1 throughout G1 with the
      maximum being 10-fold higher than that of the Rb+/+ fibroblasts. This profile of
      intracellular H1 phosphorylation corresponds with deregulated CDK2 activity
      observed in in vitro assays, suggesting that CDK2 may be directly responsible for
      the in vivo phosphorylation of H1. H1 phosphorylation has been proposed to lead
      to a relaxation of chromatin structure due to a decreased affinity of this
      protein for chromatin after phosphorylation. In accord with this, chromatin from
      the Rb-/- cells is more susceptible to micrococcal nuclease digestion than that
      from Rb+/+ fibroblasts. Increased H1 phosphorylation and relaxed chromatin
      structure have also been observed in cells expressing several oncogenes,
      suggesting a common mechanism in oncogene and tumor suppressor gene function.

PMID- 8876167
TI  - CDP/cut is the DNA-binding subunit of histone gene transcription factor HiNF-D: a
      mechanism for gene regulation at the G1/S phase cell cycle transition point
      independent of transcription factor E2F.
AB  - Transcription of the genes for the human histone proteins H4, H3, H2A, H2B, and
      H1 is activated at the G1/S phase transition of the cell cycle. We have
      previously shown that the promoter complex HiNF-D, which interacts with cell
      cycle control elements in multiple histone genes, contains the key cell cycle
      factors cyclin A, CDC2, and a retinoblastoma (pRB) protein-related protein.
      However, an intrinsic DNA-binding subunit for HiNF-D was not identified. Many
      genes that are up-regulated at the G1/S phase boundary are controlled by E2F, a
      transcription factor that associates with cyclin-, cyclin-dependent kinase-, and
      pRB-related proteins. Using gel-shift immunoassays, DNase I protection, and
      oligonucleotide competition analyses, we show that the homeodomain protein
      CDP/cut, not E2F, is the DNA-binding subunit of the HiNF-D complex. The HiNF-D
      (CDP/cut) complex with the H4 promoter is immunoreactive with antibodies against
      CDP/cut and pRB but not p107, whereas the CDP/cut complex with a nonhistone
      promoter (gp91-phox) reacts only with CDP and p107 antibodies. Thus, CDP/cut
      complexes at different gene promoters can associate with distinct pRB-related
      proteins. Transient coexpression assays show that CDP/cut modulates H4 promoter
      activity via the HiNF-D-binding site. Hence, DNA replication-dependent histone H4
      genes are regulated by an E2F-independent mechanism involving a complex of
      CDP/cut with cyclin A/CDC2/ RB-related proteins.

PMID- 8876168
TI  - Rescue of abasic hammerhead ribozymes by exogenous addition of specific bases.
AB  - We have synthesized 13 hammerhead ribozyme variants, each containing an abasic
      residue at a specific position of the catalytic core. The activity of each of the
      variants is significantly reduced. In four cases, however, activity can be
      rescued by exogenous addition of the missing base. For one variant, the rescue is
      300-fold; for another, the rescue is to the wild-type level. This latter abasic
      variant (G10.1X) has been characterized in detail. Activation is specific for
      guanine, the base initially removed. In addition, the specificity for guanine
      versus adenine is substantially altered by replacing C with U in the opposite
      strand of the ribozyme. These results show that a binding site for a small,
      noncharged ligand can be created in a preexisting ribozyme structure. This has
      implications for structure-function analysis of RNA, and leads to speculations
      about evolution in an "RNA world" and about the potential therapeutic use of
      ribozymes.

PMID- 8876169
TI  - Mutant LexA proteins with specific defects in autodigestion.
AB  - In self-processing biochemical reactions, a protein or RNA molecule specifically
      modifies its own structure. Many such reactions are regulated in response to the
      needs of the cell by an interaction with another effector molecule. In the system
      we study here, specific cleavage of the Escherichia coli LexA repressor, LexA
      cleaves itself in vitro at a slow rate, but in vivo cleavage requires interaction
      with an activated form of RecA protein. RecA acts indirectly as a coprotease to
      stimulate LexA autodigestion. We describe here a new class of lexA mutants, lexA
      (Adg-; for autodigestion-defective) mutants, termed Adg- for brevity. Adg-
      mutants specifically interfered with the ability of LexA to autodigest but left
      intact its ability to undergo RecA-mediated cleavage. The data are consistent
      with a conformational model in which RecA favors a reactive conformation capable
      of undergoing cleavage. To our knowledge, this is the first example of a mutation
      in a regulated self-processing reaction that impairs the rate of self-processing
      without markedly affecting the stimulated reaction. Had wild-type lexA carried
      such a substitution, discovery of its self-processing would have been difficult;
      we suggest that, in other systems, a slow rate of self-processing has prevented
      recognition that a reaction is of this nature.

PMID- 8876170
TI  - A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and
      type I topoisomerases.
AB  - The covalent joining of topoisomerases to DNA is normally a transient step in the
      reaction cycle of these important enzymes. However, under a variety of
      circumstances, the covalent complex is converted to a long-lived or dead-end
      product that can result in chromosome breakage and cell death. We have discovered
      and partially purified an enzyme that specifically cleaves the chemical bond that
      joins the active site tyrosine of topoisomerases to the 3' end of DNA. The
      reaction products made by the purified enzyme on a variety of model substrates
      indicate that the enzyme cleanly hydrolyzes the tyrosine-DNA phosphodiester
      linkage, thereby liberating a DNA terminated with a 3' phosphate. The wide
      distribution of this phosphodiesterase in eukaryotes and its specificity for
      tyrosine linked to the 3' end but not the 5' end of DNA suggest that it plays a
      role in the repair of DNA trapped in complexes involving eukaryotic topoisomerase
      I.

PMID- 8876171
TI  - p300 is a component of an estrogen receptor coactivator complex.
AB  - The estrogen receptor (ER) is a ligand-dependent transcription factor that
      regulates expression of target genes in response to estrogen in concert with
      other cellular signaling pathways. This suggests that the mechanism by which ER
      transmits an activating signal to the general transcription machinery may include
      factors that integrate these diverse signals. We have previously characterized
      the estrogen receptor-associated protein, ERAP160, as a factor that complexes
      with ER in an agonist-dependent manner. We have now found that the
      transcriptional coactivator p300 associates with agonist bound ER and augments
      ligand-dependent activation by ER. Our studies show that an ER coactivator
      complex involves a direct hormone-dependent interaction between ER and ERAP160,
      resulting in the recruitment of p300. In addition, antibodies directed against
      the cloned steroid receptor coactivator 1 (SRC1) recognize ERAP160. The known
      role of p300 in multiple signal transduction pathways, including those involving
      the second messenger cAMP, suggests p300 functions as a point of integration
      between ER and these other pathways.

PMID- 8876172
TI  - Detecting the conformational change of transmembrane signaling in a bacterial
      chemoreceptor by measuring effects on disulfide cross-linking in vivo.
AB  - Transmembrane signaling by bacterial chemoreceptors is thought to involve
      relative movement among the four transmembrane helices of the homodimer. We
      assayed that movement by measuring effects of ligand occupancy on rates of
      oxidative cross-linking between cysteines introduced into neighboring helices of
      the transmembrane domain of chemoreceptor Trg from Escherichia coli. Measurements
      were done on chemoreceptors in their native environment, intact cells that were
      motile and chemotactically responsive. Receptor occupancy did not appear to cause
      drastic rearrangement of the four-helix structure since, among 67 cysteine pairs
      tested, the same 19 exhibited oxidative cross-linking in the presence or absence
      of saturating chemoattractant. However, occupancy did cause subtle changes that
      were detected as effects on rates of cross-linking. Among the seven disulfides
      appropriate for measurements of initial rates of formation, ligand occupancy had
      significant and different effects on all three cross-links that connected the two
      helices within a subunit but had minimal effects on the four that spanned the
      packing interface between subunits. This constitutes direct evidence that the
      conformational change of transmembrane signaling involves significant movement
      within a subunit and minimal movement between subunits, a pattern deduced from
      several previous studies and now documented directly. Among possible modes of
      movement between the two helices of a subunit, axial sliding of one helix
      relative to the other was the conformational change that best accounted for the
      observed effects on cross-linking.

PMID- 8876173
TI  - In vitro characterization of mutant yeast RNA polymerase II with reduced binding
      for elongation factor TFIIS.
AB  - We have reported previously the isolation and genetic characterization of
      mutations in the gene encoding the largest subunit of yeast RNA polymerase II
      (RNAPII), which lead to 6-azauracil (6AU)-sensitive growth. It was suggested that
      these mutations affect the functional interaction between RNAPII and
      transcription-elongation factor TFIIS because the 6AU-sensitive phenotype of the
      mutant strains was similar to that of a strain defective in the production of
      TFIIS and can be suppressed by increasing the dosage of the yeast TFIIS-encoding
      gene, PPR2, RNAPIIs were purified and characterized from two independent 6AU
      sensitive yeast mutants and from wild-type (wt) cells. In vitro, in the absence
      of TFIIS, the purified wt polymerase and the two mutant polymerases showed
      similar specific activity in polymerization, readthrough at intrinsic
      transcriptional arrest sites and nascent RNA cleavage. In contrast to the wt
      polymerase, both mutant polymerases were not stimulated by the addition of a 3
      fold molar excess of TFIIS in assays of promoter-independent transcription,
      readthrough or cleavage. However, stimulation of the ability of the mutant
      RNAPIIs to cleave nascent RNA and to read through intrinsic arrest sites was
      observed at TFIIS:RNAPII molar ratios greater than 600:1. Consistent with these
      findings, the binding affinity of the mutant polymerases for TFIIS was found to
      be reduced by more than 50-fold compared with that of the wt enzyme. These
      studies demonstrate that TFIIS has an important role in the regulation of
      transcription by yeast RNAPII and identify a possible binding site for TFIIS on
      RNAPII.

PMID- 8876174
TI  - RNA replication by Q beta replicase: a working model.
AB  - Two classes of RNA ligands that bound to separate, high affinity nucleic acid
      binding sites on Q beta replicase were previously identified. RNA ligands to the
      two sites, referred to as site I and site II, were used to investigate the
      molecular mechanism of RNA replication employed by the four-subunit replicase.
      Replication inhibition by site I- and site II-specific ligands defined two
      subsets of replicatable RNAs. When provided with appropriate 3' ends, ligands to
      either site served as replication templates. UV crosslinking experiments revealed
      that site I is associated with the S1 subunit, site II with elongation factor Tu,
      and polymerization with the viral subunit of the holoenzyme. These results
      provide the framework for a three site model describing template recognition and
      product strand initiation by Q beta replicase.

PMID- 8876175
TI  - Selective response of ternary complex factor Sap1a to different mitogen-activated
      protein kinase subgroups.
AB  - Mitogenic and stres signals results in the activation of extracellular signal
      regulated kinases (ERKs) and stress-activated protein kinase/c-Jun N-terminal
      kinases (SAPK/JNKs), respectively, which are two subgroups of the mitogen
      activated protein kinases. A nuclear target of mitogen-activated protein (MAP)
      kinases is the ternary complex factor Elk-1, which underlies its involvement in
      the regulation of c-fos gene expression by mitogenic and stress signals. A second
      ternary complex factor, Sap1a, is coexpressed with Elk-1 in several cell types
      and shares attributes of Elk-1, the significance of which is not clear. Here we
      show that Sap1a is phosphorylated efficiently by ERKs but not by SAPK/JNKs. Serum
      response factor-dependent ternary complex formation by Sap1a is stimulated by ERK
      phosphorylation but not by SAPK/JNKs. Moreover, Sap1a-mediated transcription is
      activated by mitogenic signals but not by cell stress. These results suggest that
      Sap1a and Elk-1 have distinct physiological functions.

PMID- 8876176
TI  - The Ku-like protein from Saccharomyces cerevisiae is required in vitro for the
      assembly of a stable multiprotein complex at a eukaryotic origin of replication.
AB  - We have previously shown that three distinct DNA-binding activities, in crude
      form, are necessary for the ATP-dependent assembly of a specific and stable
      multiprotein complex at a yeast origin of replication. Here we show the
      purification of one of these DNA binding activities, referred to as origin
      binding factor 2 (OBF2). The purified protein is a heterodimer composed of two
      polypeptides with molecular mass values of 65 and 80 kDa as determined by
      SDS/PAGE. Purified OBF2 not only binds DNA but also supports the formation of a
      protein complex at essential sequences within the ARS121 origin of replication.
      Interestingly, OBF2 binds tightly and nonspecifically to both duplex DNA and
      single-stranded DNA. The interaction with duplex DNA occurs at the termini. N
      terminal sequencing of the 65-kDa subunit has revealed that this polypeptide is
      identical to the previously identified HDF1 peptide, a yeast homolog of the small
      subunit of the mammalian Ku autoantigen. Although the potential involvement of Ku
      in DNA metabolic events has been proposed, this is the first requirement for a Ku
      like protein in the assembly of a protein complex at essential sequences within a
      eukaryotic origin of replication.

PMID- 8876177
TI  - Trans-activation by human immunodeficiency virus Tat protein requires the C
      terminal domain of RNA polymerase II.
AB  - Human immunodeficiency virus (HIV)-encoded trans-activator (Tat) acts through the
      trans-activation response element RNA stem-loop to increase greatly the
      processivity of RNA polymerase II. Without Tat, transcription originating from
      the HIV promoter is attenuated. In this study, we demonstrate that
      transcriptional activation by Tat in vivo and in vitro requires the C-terminal
      domain (CTD) of RNA polymerase II. In contrast, the CTD is not required for basal
      transcription and for the formation of short, attenuated transcripts. Thus, trans
      activation by Tat resembles enhancer-dependent activation of transcription. These
      results suggest that effects of Tat on the processivity of RNA polymerase II
      require proteins that are associated with the CTD and may result in the
      phosphorylation of the CTD.

PMID- 8876178
TI  - Identification of the coding region for a second poly(A) polymerase in
      Escherichia coli.
AB  - We had earlier identified the pcnB locus as the gene for the major Escherichia
      coli poly(A) polymerase (PAP I). In this report, we describe the disruption and
      identification of a candidate gene for a second poly(A) polymerase (PAP II) by an
      experimental strategy which was based on the assumption that the viability of E.
      coli depends on the presence of either PAP I or PAP II. The coding region thus
      identified is the open reading frame f310, located at about 87 min on the E. coli
      chromosome. The following lines of evidence support f310 as the gene for PAP II:
      (i) the deduced peptide encoded by f310 has a molecular weight of 36,300, similar
      to the molecular weight of 35,000 estimated by gel filtration of PAP II; (ii) the
      deduced f310 product is a relatively hydrophobic polypeptide with a pI of 9.4,
      consistent with the properties of partially purified PAP II; (iii) overexpression
      of f310 leads to the formation of inclusion bodies whose solubilization and
      renaturation yields poly(A) polymerase activity that corresponds to a 35-kDa
      protein as shown by enzyme blotting; and (iv) expression of a f310 fusion
      construct with hexahistidine at the N-terminus of the coding region allowed
      purification of a poly(A) polymerase fraction whose major component is a 36-kDa
      protein. E. coli PAP II has no significant sequence homology either to PAP I or
      to the viral and eukaryotic poly(A) polymerases, suggesting that the bacterial
      poly(A) polymerases have evolved independently. An interesting feature of the PAP
      II sequence is the presence of sets of two paired cysteine and histidine residues
      that resemble the RNA binding motifs seen in some other proteins.

PMID- 8876179
TI  - UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in
      Cockayne syndrome cells.
AB  - Damage to actively transcribed DNA is preferentially repaired by the
      transcription-coupled repair (TCR) system. TCR requires RNA polymerase II (Pol
      II), but the mechanism by which repair enzymes preferentially recognize and
      repair DNA lesions on Pol II-transcribed genes is incompletely understood. Herein
      we demonstrate that a fraction of the large subunit of Pol II (Pol II LS) is
      ubiquitinated after exposing cells to UV-radiation or cisplatin but not several
      other DNA damaging agents. This novel covalent modification of Pol II LS occurs
      within 15 min of exposing cells to UV-radiation and persists for about 8-12 hr.
      Ubiquitinated Pol II LS is also phosphorylated on the C-terminal domain. UV
      induced ubiquitination of Pol II LS is deficient in fibroblasts from individuals
      with two forms of Cockayne syndrome (CS-A and CS-B), a rare disorder in which TCR
      is disrupted. UV-induced ubiquitination of Pol II LS can be restored by
      introducing cDNA constructs encoding the CSA or CSB genes, respectively, into CS
      A or CS-B fibroblasts. These results suggest that ubiquitination of Pol II LS
      plays a role in the recognition and/or repair of damage to actively transcribed
      genes. Alternatively, these findings may reflect a role played by the CSA and CSB
      gene products in transcription.

PMID- 8876180
TI  - Random circular permutation of genes and expressed polypeptide chains:
      application of the method to the catalytic chains of aspartate transcarbamoylase.
AB  - Recent studies on proteins whose N and C termini are in close proximity have
      demonstrated that folding of polypeptide chains and assembly of oligomers can be
      accomplished with circularly permuted chains. As yet no methodical study has been
      conducted to determine how extensively new termini can be introduced and where
      such termini cannot be tolerated. We have devised a procedure to generate random
      circular permutations of the catalytic chains of Escherichia coli aspartate
      transcarbamoylase (ATCase; EC 2.1.3.2) and to select clones that produce active
      or stable holoenzyme containing permuted chains. A tandem gene construct was
      made, based on the desired linkage between amino acid residues in the C- and N
      terminal regions of the polypeptide chain, and this DNA was treated with a
      suitable restriction enzyme to yield a fragment containing the rearranged coding
      sequence for the chain. Circularization achieved with DNA ligase, followed by
      linearization at random with DNase I, and incorporation of the linearized,
      repaired, blunt-ended, rearranged genes into a suitable plasmid permitted the
      expression of randomly permuted polypeptide chains. The plasmid with appropriate
      stop codons also contained pyrI, the gene encoding the regulatory chain of
      ATCase. Colonies expressing detectable amounts of ATCase-like molecules
      containing permuted catalytic chains were identified by an immunoblot technique
      or by their ability to grow in the absence of pyrimidines in the growth medium.
      Sequencing of positive clones revealed a variety of novel circular permutations.
      Some had N and C termini within helices of the wild-type enzyme as well as
      deletions and insertions. Permutations were concentrated in the C-terminal domain
      and only few were detected in the N-terminal domain. The technique, which is
      adaptable generally to proteins whose N and C termini are near each other, can be
      of value in relating in vivo folding of nascent, growing polypeptide chains to in
      vitro renaturation of complete chains and determining the role of protein
      sequence in folding kinetics.

PMID- 8876181
TI  - p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear
      antigen into the DNA replication complex.
AB  - Fen1 or maturation factor 1 is a 5'-3' exonuclease essential for the degradation
      of the RNA primer-DNA junctions at the 5' ends of immature Okazaki fragments
      prior to their ligation into a continuous DNA strand. The gene is also necessary
      for repair of damaged DNA in yeast. We report that human proliferating-cell
      nuclear antigen (PCNA) associates with human Fen1 with a Kd of 60 nM and an
      apparent stoichiometry of three Fen1 molecules per PCNA trimer. The Fen1-PCNA
      association is seen in cell extracts without overexpression of either partner and
      is mediated by a basic region at the C terminus of Fen1. Therefore, the
      polymerase delta-PCNA-Fen1 complex has all the activities associated with
      prokaryotic DNA polymerases involved in replication: 5'-3' polymerase, 3'-5'
      exonuclease, and 5'-3' exonuclease. Although p21, a regulatory protein induced by
      p53 in response to DNA damage, interacts with PCNA with a comparable Kd (10 nM)
      and a stoichiometry of three molecules of p21 per PCNA trimer, a p21-PCNA-Fen1
      complex is not formed. This mutually exclusive interaction suggests that the
      conformation of a PCNA trimer switches such that it can either bind p21 or Fen1.
      Furthermore, overexpression of p21 can disrupt Fen1-PCNA interaction in vivo.
      Therefore, besides interfering with the processivity of polymerase delta-PCNA,
      p21 also uncouples Fen1 from the PCNA scaffold.

PMID- 8876182
TI  - Silver ion high pressure liquid chromatography provides unprecedented separation
      of sterols: application to the enzymatic formation of cholesta-5,8-dien-3 beta
      ol.
AB  - We report that silver ion HPLC provides remarkable separations of C27 sterols
      differing only in the number or location of olefinic double bonds. This technique
      has been extended to LC-MS, analysis of purified components by GC, GC-MS, and 1H
      NMR, and to its use on a semipreparative scale. The application of this
      methodology for the demonstration of the catalysis, by rat liver microsomes, of
      the conversion of 7-dehydrocholesterol to cholesta-5,8-dien-3 beta-ol is also
      presented.

PMID- 8876183
TI  - Intrinsic compressibility and volume compression in solvated proteins by
      molecular dynamics simulation at high pressure.
AB  - Constant pressure and temperature molecular dynamics techniques have been
      employed to investigate the changes in structure and volumes of two globular
      proteins, superoxide dismutase and lysozyme, under pressure. Compression (the
      relative changes in the proteins' volumes), computed with the Voronoi technique,
      is closely related with the so-called protein intrinsic compressibility,
      estimated by sound velocity measurements. In particular, compression computed
      with Voronoi volumes predicts, in agreement with experimental estimates, a
      negative bound water contribution to the apparent protein compression. While the
      use of van der Waals and molecular volumes underestimates the intrinsic
      compressibilities of proteins, Voronoi volumes produce results closer to
      experimental estimates. Remarkably, for two globular proteins of very different
      secondary structures, we compute identical (within statistical error) protein
      intrinsic compressions, as predicted by recent experimental studies. Changes in
      the protein interatomic distances under compression are also investigated. It is
      found that, on average, short distances compress less than longer ones. This
      nonuniform contraction underlines the peculiar nature of the structural changes
      due to pressure in contrast with temperature effects, which instead produce
      spatially uniform changes in proteins. The structural effects observed in the
      simulations at high pressure can explain protein compressibility measurements
      carried out by fluorimetric and hole burning techniques. Finally, the calculation
      of the proteins static structure factor shows significant shifts in the peaks at
      short wavenumber as pressure changes. These effects might provide an alternative
      way to obtain information concerning compressibilities of selected protein
      regions.

PMID- 8876184
TI  - Diffusion-limited contact formation in unfolded cytochrome c: estimating the
      maximum rate of protein folding.
AB  - How fast can a protein fold? The rate of polypeptide collapse to a compact state
      sets an upper limit to the rate of folding. Collapse may in turn be limited by
      the rate of intrachain diffusion. To address this question, we have determined
      the rate at which two regions of an unfolded protein are brought into contact by
      diffusion. Our nanosecond-resolved spectroscopy shows that under strongly
      denaturing conditions, regions of unfolded cytochrome separated by approximately
      50 residues diffuse together in 35-40 microseconds. This result leads to an
      estimate of approximately (1 microsecond)-1 as the upper limit for the rate of
      protein folding.

PMID- 8876185
TI  - Electric-field-induced Schiff-base deprotonation in D85N mutant
      bacteriorhodopsin.
AB  - The application of an external electric field to dry films of Asp-85-->Asn mutant
      bacteriorhodopsin causes deprotonation of the Schiff base, resulting in a shift
      of the optical absorption maximum from 600 nm to 400 nm. This is in marked
      contrast to the case of wild-type bacteriorhodopsin films, in which electric
      fields produce a red-shifted product whose optical properties are similar to
      those of the acid-blue form of the protein. This difference is due to the much
      weaker binding of the Schiff-base proton in the mutant protein, as indicated by
      its low pK of approximately 9, as compared with the value pK approximately 13 in
      the wild type. Other bacteriorhodopsins with lowered Schiff-base pK values should
      also exhibit a field-induced shift in the protonation equilibrium of the Schiff
      base. We propose mechanisms to account for these observations.

PMID- 8876186
TI  - Interplay of structure and disorder in cochaperonin mobile loops.
AB  - Protein-protein interactions typically are characterized by highly specific
      interfaces that mediate binding with precisely tuned affinities. Binding of the
      Escherichia coli cochaperonin GroES to chaperonin GroEL is mediated, at least in
      part, by a mobile polypeptide loop in GroES that becomes immobilized in the
      GroEL/GroES/nucleotide complex. The bacteriophage T4 cochaperonin Gp31 possesses
      a similar highly flexible polypeptide loop in a region of the protein that shows
      low, but significant, amino acid similarity with GroES and other cochaperonins.
      When bound to GroEL, a synthetic peptide representing the mobile loop of either
      GroES or Gp31 adopts a characteristic bulged hairpin conformation as determined
      by transferred nuclear Overhauser effects in NMR spectra. Thermodynamic
      considerations suggest that flexible disorder in the cochaperonin mobile loops
      moderates their affinity for GroEL to facilitate cycles of chaperonin-mediated
      protein folding.

PMID- 8876187
TI  - An iterative method for extracting energy-like quantities from protein
      structures.
AB  - We present a method (ENERGI) for extracting energy-like quantities from a data
      base of protein structures. In this paper, we use the method to generate pairwise
      additive amino acid "energy" scores. These scores are obtained by iteration until
      they correctly discriminate a set of known protein folds from decoy
      conformations. The method succeeds in lattice model tests and in the gapless
      threading problem as defined by Maiorov and Crippen [Maiorov, V. N. & Crippen, G.
      M. (1992) J. Mol. Biol. 227, 876-888]. A more challenging test of threading a
      larger set of test proteins derived from the representative set of Hobohm and
      Sander [Hobohm, U. & Sander, C. (1994) Protein Sci. 3, 522-524] is used as a
      "workbench" for exploring how the ENERGI scores depend on their parameter sets.

PMID- 8876188
TI  - Transbilayer inhibition of protein kinase C by the lipophosphoglycan from
      Leishmania donovani.
AB  - Lipophosphoglycan (LPG), the predominant molecule on the surface of the parasite
      Leishmania donovani, has previously been shown to be a potent inhibitor of
      protein kinase C (PKC) isolated from rat brain. The mechanism by which LPG
      inhibits PKC was further investigated in this study. LPG was found to inhibit the
      PKC alpha-catalyzed phosphorylation of histone in assays using large unilamellar
      vesicles composed of 1-palmitoyl, 2-oleoyl phosphatidylserine and 1-palmitoyl, 2
      oleoyl phosphatidylcholine either with or without 1% 1,2 diolein added. The
      results also indicated that while PKC binding to sucrose-loaded vesicles was not
      substantially reduced in the presence of LPG at concentrations of 1-2%, the
      activity of membrane-bound PKC was inhibited by 70%. This inhibition of the
      membrane-bound form of PKC is not a consequence of reduced substrate availability
      to the membrane. However, Km shifted from approximately 31 +/- 4 microM to 105 +/
      26 microM in the presence of 5% LPG. LPG caused PKC to bind to membranes without
      inducing a conformational change as revealed by the lack of an increased
      susceptibility to trypsin. An LPG fragment containing only one repeating
      disaccharide unit was not as effective as the entire LPG molecule or of larger
      fragments in inhibiting the membrane-bound form of the enzyme. The shorter
      fragments were also less potent in raising the bilayer to hexagonal phase
      transition temperature of a model membrane. LPG is also able to inhibit the
      membrane-bound form of PKC alpha from the inner monolayer of large unilamellar
      vesicles, the opposite monolayer to which the enzyme binds in our assay.
      Inhibition is likely a result of alterations in the physical properties of the
      membrane. To our knowledge, this is the first example of a membrane additive that
      can inhibit the membrane-bound form of PKC in the presence of other lipid
      cofactors.

PMID- 8876189
TI  - Profluorescent protease substrates: intramolecular dimers described by the
      exciton model.
AB  - Xanthene dyes are known to form dimers with spectral characteristics that have
      been interpreted in terms of exciton theory. A unique aspect of H-type dimers is
      the fluorescence quenching that accompanies their formation. Using the principles
      of exciton theory as a guide, a series of protease substrates was synthesized
      with a xanthene dye on each side of the cleavage site. To bring the attached dyes
      into spatial proximity to form a dimer, the molecular design included structure
      determinant regions in the amino acid sequence. In addition, chromophores were
      chosen such that changes in absorption spectra indicative of exciton splitting
      were anticipated. Cleavage of the peptides by a protease resulted in disruption
      of the dimers and indeed significant absorption spectral changes were observed.
      Furthermore, substrate cleavage was accompanied by at least an order of magnitude
      increase in fluorescence intensity. This has allowed determination of
      intracellular elastase activity using a fluorescence microscope equipped with
      standard optics.

PMID- 8876190
TI  - Transposition of DNase hypersensitive chromatin to the nuclear periphery
      coincides temporally with nerve growth factor-induced up-regulation of gene
      expression in PC12 cells.
AB  - To test the hypothesis that the nonrandom organization of the contents of
      interphase nuclei represents a compartmentalization of function, we examined the
      relative, spatial relationship of small nuclear ribonucleoproteins (snRNPs) and
      of DNase I hypersensitive chromatin (DHC) in rat pheochromocytoma cells. In
      controls, DHC and snRNPs colocalized as pan-nuclear speckles. During nerve growth
      factor-induced differentiation, both snRNPs and DHC migrated to the nuclear
      periphery with the migration of DHC preceding that of snRNPs, resulting in their
      transient separation. The formation of DHC shells temporally coincided with an up
      regulation of neurofilament light chain mRNA. This indicates that the expression
      of this sequence may be associated with its spatial transposition to the nuclear
      periphery.

PMID- 8876191
TI  - Single residue substitutions that change the gating properties of a
      mechanosensitive channel in Escherichia coli.
AB  - MscL is a channel that opens a large pore in the Escherichia coli cytoplasmic
      membrane in response to mechanical stress. Previously, we highly enriched the
      MscL protein by using patch clamp as a functional assay and cloned the
      corresponding gene. The predicted protein contains a largely hydrophobic core
      spanning two-thirds of the molecule and a more hydrophilic carboxyl terminal
      tail. Because MscL had no homology to characterized proteins, it was impossible
      to predict functional regions of the protein by simple inspection. Here, by
      mutagenesis, we have searched for functionally important regions of this
      molecule. We show that a short deletion from the amino terminus (3 amino acids),
      and a larger deletion of 27 amino acids from the carboxyl terminus of this
      protein, had little if any effect in channel properties. We have thus narrowed
      the search of the core mechanosensitive mechanism to 106 residues of this 136
      amino acid protein. In contrast, single residue substitutions of a lysine in the
      putative first transmembrane domain or a glutamine in the periplasmic loop caused
      pronounced shifts in the mechano-sensitivity curves and/or large changes in the
      kinetics of channel gating, suggesting that the conformational structure in these
      regions is critical for normal mechanosensitive channel gating.

PMID- 8876192
TI  - Production of infectious recombinant Moloney murine leukemia virus particles in
      BHK cells using Semliki Forest virus-derived RNA expression vectors.
AB  - We describe a heterologous, Semliki Forest virus (SFV)-driven packaging system
      for the production of infectious recombinant Moloney murine leukemia virus
      particles. The gag-pol and env genes, as well as a recombinant retrovirus genome
      (LTR-psi (+)-neoR-LTR), were inserted into individual SFV1 expression plasmids.
      Replication-competent RNAs were transcribed in vitro and introduced into the
      cytoplasm of BHK-21 cells using electroporation. The expressed Moloney murine
      leukemia virus structural proteins produced extracellular virus-like particles.
      In these particles the gag precursor was processed into mature products,
      indicating that the particles contained an active protease. The protease of the
      gag-pol fusion protein was also shown to be active in a trans-complementation
      assay using a large excess of Pr65gag. Moreover, the particles possessed reverse
      transcriptase (RT) activity as measured in an in vitro assay. Cotransfection of
      BHK-21 cells by all three SFV1 constructs resulted in the production of
      transduction-competent particles at 4 x 10(6) colony-forming units (cfu)/ml
      during a 5-hr incubation period. Altogether, 2.9 x 10(7) transduction-competent
      particles were obtained from about 4 x 10(6) transfected cells. Thus, this system
      represents the first RNA-based packaging system for the production of infectious
      retroviral particles. The facts that no helper virus could be detected in the
      virus stocks and that particles carrying the amphotropic envelope could be
      produced with similar efficiency as those that carry the ecotropic envelope make
      the system very interesting for gene therapy.

PMID- 8876193
TI  - Microtubules mediate mitochondrial distribution in fission yeast.
AB  - The Schizosaccharomyces pombe mutant, ban5-4, displays aberrant mitochondrial
      distribution. Incubation of this conditional-lethal mutant at the nonpermissive
      temperature led to aggregated mitochondria that were distributed asymmetrically
      within the cell. Development of this mitochondrial asymmetry but not
      mitochondrial aggregation required progression through the cell division cycle.
      Genetic analysis revealed that ban5-4 is an allele of atb2 encoding alpha 2
      tubulin. Consistent with this finding, cells with the cold-sensitive nda3
      mutation in beta-tubulin displayed aggregated and asymmetrically distributed
      mitochondria after incubation at lowered temperatures. These results indicate
      that microtubules mediate mitochondrial distribution in fission yeast and provide
      the first genetic evidence for the role of microtubules in mitochondrial
      movement.

PMID- 8876194
TI  - Maspin acts at the cell membrane to inhibit invasion and motility of mammary and
      prostatic cancer cells.
AB  - Maspin, a novel serine protease inhibitor (serpin), inhibits tumor invasion and
      metastasis of mammary carcinoma. We show here that recombinant maspin protein
      blocks the motility of these carcinoma cells in culture over 12 h, as
      demonstrated by time-lapse video microscopy. Lamellopodia are withdrawn but
      ruffling continues. Both exogenous recombinant maspin and maspin expressed by
      tumor transfectants exhibit inhibitory effects on cell motility and cell invasion
      as shown in modified Boyden chamber assays. In addition, three prostatic cancer
      cell lines treated with recombinant maspin exhibited similar inhibition of both
      invasion and motility, suggesting a similar mode of maspin action in these two
      glandular epithelial cancers. When mammary carcinoma cells were treated with
      recombinant maspin, the protein was shown by immunostaining to bind specifically
      to the cell surface, suggesting that maspin activity is membrane associated. When
      pretreated with antimaspin antibody, maspin loses its inhibitory effects on both
      invasion and motility. However, when maspin is added to these cells preceding
      antibody treatment, the activity of maspin is no longer inhibited by subsequent
      addition of the antibody. It is concluded therefore that the inhibition of
      invasion and motility by maspin is initially localized to the cell surface.

PMID- 8876195
TI  - Identification of a c-fos-induced gene that is related to the platelet-derived
      growth factor/vascular endothelial growth factor family.
AB  - Using a mRNA differential screening of fibroblasts differing for the expression
      of c-fos we isolated a c-fos-induced growth factor (FIGF). The deduced protein
      sequence predicts that the cDNA codes for a new member of the platelet-derived
      growth factor/vascular endothelial growth factor (PDGF/VEGF) family. Northern
      blot analysis shows that FIGF expression is strongly reduced in c-fos-deficient
      cells. Transfection of exogenous c-fos driven by a constitutive promoter restores
      the FIGF expression in these cells. In contrast, both PDGF and VEGF expression is
      unaffected by c-fos. FIGF is a secreted dimeric protein able to stimulate
      mitogenic activity in fibroblasts. FIGF overexpression induces morphological
      alterations in fibroblasts. The cells acquire a spindle-shaped morphology, become
      more refractive, disorganized, and detach from the plate. These results imply
      that FIGF is a downstream growth and morphogenic effector of c-fos. These results
      also suggest that the expression of FIGF in response to c-fos activation induces
      specific differentiation patterns and its aberrant activation contributes to the
      malignant phenotype of tumors.

PMID- 8876196
TI  - The cytokine-activated tyrosine kinase JAK2 activates Raf-1 in a p21ras-dependent
      manner.
AB  - JAK2, a member of the Janus kinase superfamily was found to interact functionally
      with Raf-1, a central component of the ras/mitogen-activated protein kinase
      signal transduction pathway. Interferon-gamma and several other cytokines that
      are known to activate JAK2 kinase were also found to stimulate Raf-1 kinase
      activity toward MEK-1 in mammalian cells. In the baculovirus coexpression system,
      Raf-1 was activated by JAK2 in the presence of p21ras. Under these conditions, a
      ternary complex of p21ras, JAK2, and Raf-1 was observed. In contrast, in the
      absence of p21ras, coexpression of JAK2 and Raf-1 resulted in an overall decrease
      in the Raf-1 kinase activity. In addition, JAK2 phosphorylated Raf-1 at sites
      different from those phosphorylated by pp60v-src. In mammalian cells treated with
      either erythropoietin or interferon-gamma, a small fraction of Raf-1
      coimmunoprecipitated with JAK2 in lysates of cells in which JAK2 was activated as
      judged by its state of tyrosine phosphorylation. Taken together, these data
      suggest that JAK2 and p21ras cooperate to activate Raf-1.

PMID- 8876197
TI  - Cell cycling and patterned cell proliferation in the Drosophila wing during
      metamorphosis.
AB  - In metamorphosing wing discs, progression through the cell cycle takes place, as
      in larval discs, in nonclonally derived clusters of cells synchronized in the
      same cell cycle stage. Contrary to early discs, there are temporal and spatial
      heterogeneities in cell proliferation associated with wing margin, vein,
      intervein, and middle intervein territories. Within these territories, there are
      no indications of a wave progression of the cell cycle. Mitotic orientations are,
      as in early discs, at random but there is a preferential allocation of
      postmitotic cells along the proximodistal axis, thus explaining the elongated
      shape of the resulting clones along this axis. Shapes of clones in mature discs
      and in evaginated wings are similar, thus excluding major morphogenetic movements
      during evagination. After the proliferative period, all the cells are arrested in
      G1 phase. The final number of cells of the wing is fixed independently of
      experimental perturbations that alter the cell division schedule. These results
      are discussed in the context of a model of wing morphogenesis.

PMID- 8876201
TI  - Nocturnality and species survival.
AB  - Surveys of butterfly and moth diversity in tropical forest fragments suggest that
      nocturnality confers a dispersal, and possibly a survival, advantage. The
      butterfly faunas of smaller fragments were depauperate; in contrast, the species
      richness of nocturnal moths was similar in all fragments and even in pasture. The
      lack of correlation between butterfly and moth species richness among fragments
      (r2 = 0.005) is best explained by movements of moths at night when ambient
      conditions in forest and pasture are most similar; butterflies face substantial
      daytime temperature, humidity, and solar radiation barriers. This interpretation
      is supported by information on birds, beetles, and bats.

PMID- 8876199
TI  - Oxytocin is required for nursing but is not essential for parturition or
      reproductive behavior.
AB  - Oxytocin, a neurohypophyseal hormone, has been traditionally considered essential
      for mammalian reproduction. In addition to uterine contractions during labor and
      milk ejection during nursing, oxytocin has been implicated in anterior pituitary
      function, paracrine effects in the testis and ovary and the neural control of
      maternal and sexual behaviors. To determine the essential role(s) of oxytocin in
      mammalian reproductive function, mice deficient in oxytocin have been generated
      using embryonic stem cell technology. A deletion of exon 1 encoding the oxytocin
      peptide was generated in embryonic stem cells at a high frequency and was
      successfully transmitted in the germ line. Southern blot analysis of genomic DNA
      from homozygote offspring and in situ hybridization with an exonic probe 3' of
      the deletion failed to detect any oxytocin or neurophysin sequences,
      respectively, confirming that the mutation was a null mutation. Mice lacking
      oxytocin are both viable and fertile. Males do not have any reproductive
      behavioral or functional defects in the absence of oxytocin. Similarly, females
      lacking oxytocin have no obvious deficits in fertility or reproduction, including
      gestation and parturition. However, although oxytocin-deficient females
      demonstrate normal maternal behavior, all offspring die shortly after birth
      because of the dam's inability to nurse. Postpartum injections of oxytocin to the
      oxytocin deficient mothers restore milk ejection and rescue the offspring. Thus,
      despite the multiple reproductive activities that have been attributed to
      oxytocin, oxytocin plays an essential role only in milk ejection in the mouse.

PMID- 8876198
TI  - Nuclear LIM interactor, a rhombotin and LIM homeodomain interacting protein, is
      expressed early in neuronal development.
AB  - LIM domain-containing transcription factors, including the LIM-only rhombotins
      and LIM-homeodomain proteins, are crucial for cell fate determination of
      erythroid and neuronal lineages. The zinc-binding LIM domains mediate protein
      protein interactions, and interactions between nuclear LIM proteins and
      transcription factors with restricted expression patterns have been demonstrated.
      We have isolated a novel protein, nuclear LIM interactor (NLI), that specifically
      associates with a single LIM domain in all nuclear LIM proteins tested. NLI is
      expressed in the nuclei of diverse neuronal cell types and is coexpressed with a
      target interactor islet-1 (Isl1) during the initial stages of motor neuron
      differentiation, suggesting the mutual involvement of these proteins in the
      differentiation process. The broad range of interactions between NLI and LIM
      containing transcription factors suggests the utilization of a common mechanism
      to impart unique cell fate instructions.

PMID- 8876203
TI  - Common endocrine and genetic mechanisms of behavioral development in male and
      worker honey bees and the evolution of division of labor.
AB  - Temporal polyethism is a highly derived form of behavioral development displayed
      by social insects. Hormonal and genetic mechanisms regulating temporal polyethism
      in worker honey bees have been identified, but the evolution of these mechanisms
      is not well understood. We performed three experiments with male honey bees
      (drones) to investigate how mechanisms regulating temporal polyethism may have
      evolved because, relative to workers, drones display an intriguing combination of
      similarities and differences in behavioral development. We report that behavioral
      development in drones is regulated by mechanisms common to workers. In experiment
      1, drones treated with the juvenile hormone (JH) analog methoprene started flying
      at significantly younger ages than did control drones, as is the case for
      workers. In experiment 2, there was an age-related increase in JH associated with
      the onset of drone flight, as in workers. In experiment 3, drones derived from
      workers with fast rates of behavioral development themselves started flying at
      younger ages than drones derived from workers with slower rates of behavioral
      development. These results suggest that endocrine and genetic mechanisms
      associated with temporal polyethism did not evolve strictly within the context of
      worker social behavior.

PMID- 8876204
TI  - Sex ratio adjustment in relation to paternal attractiveness in a wild bird
      population.
AB  - When the relative fitness of sons and daughters differs, sex-allocation theory
      predicts that it would be adaptive for individuals to adjust their investment in
      different sexes of offspring. Sex ratio adjustment by females in response to the
      sexual attractiveness of their mate would be an example of this. In vertebrates
      the existence of this form of sex ratio adjustment is controversial and may be
      confounded with sex-biased mortality, particularly in sexually size-dimorphic
      species. Here we use PCR amplification of a conserved W-chromosome-linked gene to
      show that the sex ratio within broods of a natural population of sexually size
      monomorphic collared flycatchers Ficedula albicollis is related to the size of
      their father's forehead patch, a heritable secondary sexual character implicated
      in female choice. Experimental manipulations of paternal investment, which
      influence the size of his character in future breeding attempts, result in
      corresponding changes in the sex ratio of offspring born to males in those
      breeding attempts. In contrast, manipulations of maternal investment have no
      effect on future sex ratios, and there is no relationship between variables
      predicting the reproductive value of the brood and nestling sex ratio. Analysis
      of recruitment of offspring reveals similar patterns of sex ratio bias. The
      results suggest that female collared flycatchers be able to adjust the sex ratio
      of eggs ovulated in response to the phenotype of their mate. This finding is most
      consistent with "genetic quality" models of sexual selection.

PMID- 8876205
TI  - Molecular clock or erratic evolution? A tale of two genes.
AB  - We have investigated the evolution of glycerol-3-phosphate dehydrogenase (Gpdh).
      The rate of amino acid replacements is 1 x 10(-10)/site/year when Drosophila
      species are compared. The rate is 2.7 times greater when Drosophila and Chymomyza
      species are compared; and about 5 times greater when any of those species are
      compared with the medfly Ceratitis capitata. This rate of 5 x 10(-10)/site/year
      is also the rate observed in comparisons between mammals, or between different
      animal phyla, or between the three multicellular kingdoms. We have also studied
      the evolution of Cu,Zn superoxide dismutase (Sod). The rate of amino acid
      replacements is about 17 x 10(-10)/site/year when comparisons are made between
      dipterans or between mammals, but only 5 x 10(-10) when animal phyla are
      compared, and only 3 x 10(-10) when the multicellular kingdoms are compared. The
      apparent decrease by about a factor of 5 in the rate of SOD evolution as the
      divergence between species increases can be consistent with the molecular clock
      hypothesis by assuming the covarion hypothesis (namely, that the number of amino
      acids that can change is constant, but the set of such amino acids changes from
      time to time and from lineage to lineage). However, we know of no model
      consistent with the molecular clock hypothesis that would account for the
      increase in the rate of GPDH evolution as the divergence between species
      increases.

PMID- 8876206
TI  - Evolution of alcohol dehydrogenase genes in the palm and grass families.
AB  - The alcohol dehydrogenase (Adh; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene
      family has two or three loci in a broad array of angiosperm species. The relative
      stability in the number of Adh loci led Gottlieb [Gottlieb, L. D. (1982) Science
      216, 373-380] to propose that the Adh gene family arose from an ancient gene
      duplication. In this study, the isolation of three loci from the California fan
      palm (Washingtonia robusta) is reported. The three loci from palm are highly
      diverged. One palm Adh gene, referred to here as adhB, has been completely
      sequenced, including 950 nucleotides of the upstream regulatory region. For the
      second locus, adhA, 81% of the exon sequence is complete. Both show the same
      basic structure as grass Adh genes in terms of intron number and intron location.
      The third locus, adhC, for which only a small amount of sequence is available
      (12% of exon sequence) appears to be more highly diverged. Comparison of the Adh
      gene families from palms and grasses shows that the adh1 and adh2 genes of
      grasses, and the adhA and adhB genes of palms, arose by duplication following the
      divergence of the two families. This finding suggests that the multiple Adh loci
      in different monocot lineages are not the result of a single ancestral
      duplication but, rather, of multiple duplication events.

PMID- 8876207
TI  - Island colonization and evolution of the insular woody habit in Echium L.
      (Boraginaceae).
AB  - Numerous island-inhabiting species of predominantly herbaceous angiosperm genera
      are woody shrubs or trees. Such "insular woodiness" is strongly manifested in the
      genus Echium, in which the continental species of circummediterranean
      distribution are herbaceous, whereas endemic species of islands along the
      Atlantic coast of north Africa are woody perennial shrubs. The history of 37
      Echium species was traced with 70 kb of noncoding DNA determined from both
      chloroplast and nuclear genomes. In all, 239 polymorphic positions with 137
      informative sites, in addition to 27 informative indels, were found. Island
      dwelling Echium species are shown to descend from herbaceous continental
      ancestors via a single island colonization event that occurred < 20 million years
      ago. Founding colonization appears to have taken place on the Canary Islands,
      from which the Madeira and Cape Verde archipelagos were invaded. Colonization of
      island habitats correlates with a recent origin of perennial woodiness from
      herbaceous habit and was furthermore accompanied by intense speciation, which
      brought forth remarkable diversity of forms among contemporary island endemics.
      We argue that the origin of insular woodiness involved response to counter
      selection of inbreeding depression in founding island colonies.

PMID- 8876208
TI  - Resistance gene analogs are conserved and clustered in soybean.
AB  - Sequences of cloned resistance genes from a wide range of plant taxa reveal
      significant similarities in sequence homology and structural motifs. This is
      observed among genes conferring resistance to viral, bacterial, and fungal
      pathogens. In this study, oligonucleotide primers designed for conserved
      sequences from coding regions of disease resistance genes N (tobacco), RPS2
      (Arabidopsis) and L6 (flax) were used to amplify related sequences from soybean
      [Glycine max (L.) Merr.]. Sequencing of amplification products indicated that at
      least nine classes of resistance gene analogs (RGAs) were detected. Genetic
      mapping of members of these classes located them to eight different linkage
      groups. Several RGA loci mapped near known resistance genes. A bacterial
      artificial chromosome library of soybean DNA was screened using primers and
      probes specific for eight RGA classes and clones were identified containing
      sequences unique to seven classes. Individual bacterial artificial chromosomes
      contained 2-10 members of single RGA classes. Clustering and sequence similarity
      of members of RGA classes suggests a common process in their evolution. Our data
      indicate that it may be possible to use sequence homologies from conserved motifs
      of cloned resistance genes to identify candidate resistance loci from widely
      diverse plant taxa.

PMID- 8876209
TI  - Isolation of a superfamily of candidate disease-resistance genes in soybean based
      on a conserved nucleotide-binding site.
AB  - The tobacco N and Arabidopsis RPS2 genes, among several recently cloned disease
      resistance genes, share highly conserved structure, a nucleotide-binding site
      (NBS). Using degenerate oligonucleotide primers for the NBS region of N and RPS2,
      we have amplified and cloned the NBS sequences from soybean. Each of these PCR
      derived NBS clones detected low-or moderate-copy soybean DNA sequences and
      belongs to 1 of 11 different classes. Sequence analysis showed that all PCR
      clones encode three motifs (P-loop, kinase-2, and kinase-3a) of NBS nearly
      identical to those in N and RPS2. The intervening region between P-loop and
      kinase-3a of the 11 classes has high (26% average) amino acid sequence similarity
      to the N gene although not as high (19% average) to RPS2. These 11 classes
      represent a superfamily of NBS-containing soybean genes that are homologous to N
      and RPS2. Each class or subfamily was assessed for its positional association
      with known soybean disease-resistance genes through near-isogenic line assays,
      followed by linkage analysis in F2 populations using restriction fragment length
      polymorphisms. Five of the 11 subfamilies have thus far been mapped to the
      vicinity of known soybean genes for resistance to potyviruses (Rsv1 and Rpv),
      Phytophthora root rot (Rps1, Rps2, and Rps3), and powdery mildew (rmd). The
      conserved N- or RPS2-homologous NBS sequences and their positional associations
      with mapped soybean-resistance genes suggest that a number of the soybean disease
      resistance genes may belong to this superfamily. The candidate subfamilies of NBS
      containing genes identified by genetic mapping should greatly facilitate the
      molecular cloning of disease-resistance genes.

PMID- 8876210
TI  - Switch from monoallelic to biallelic human IGF2 promoter methylation during aging
      and carcinogenesis.
AB  - We have previously linked aging, carcinogenesis, and de novo methylation within
      the promoter of the estrogen receptor (ER) gene in human colon. We now examine
      the dynamics of this process for the imprinted gene for insulin-like growth
      factor II (IGF2). In young individuals, the P2-4 promoters of IGF2 are methylated
      exclusively on the silenced maternal allele. During aging, this promoter
      methylation becomes more extensive and involves the originally unmethylated
      allele. Most adult human tumors, including colon, breast, lung, and leukemias,
      exhibit increased methylation at the P2-4 IGF2 promoters, suggesting further
      spreading during the neoplastic process. In tumors, this methylation is
      associated with diminished or absent IGF2 expression from the methylated P3
      promoter but maintained expression from P1, an upstream promoter that is not
      contained within the IGF2 CpG island. Our results demonstrate a remarkable
      evolution of methylation patterns in the imprinted promoter of the IGF2 gene
      during aging and carcinogenesis, and provide further evidence for a potential
      link between aberrant methylation and diseases of aging.

PMID- 8876211
TI  - A cytoplasmic male sterility-associated mitochondrial protein causes pollen
      disruption in transgenic tobacco.
AB  - In higher plants, dominant mitochondrial mutations are associated with pollen
      sterility. This phenomenon is known as cytoplasmic male sterility (CMS). It is
      thought that the disruption in pollen development is a consequence of
      mitochondrial dysfunction. To provide definitive evidence that expression of an
      abnormal mitochondrial gene can interrupt pollen development, a CMS-associated
      mitochondrial DNA sequence from common bean, orf239, was introduced into the
      tobacco nuclear genome. Several transformants containing the orf239 gene
      constructs, with or without a mitochondrial targeting sequence, exhibited a semi
      sterile or male-sterile phenotype. Expression of the gene fusions in transformed
      anthers was confirmed using RNA gel blotting, ELISA, and light and electron
      microscopic immunocytochemistry. Immunocytological analysis showed that the
      ORF239 protein could associate with the cell wall of aberrant developing
      microspores. This pattern of extracellular localization was earlier observed in
      the CMS common bean line containing orf239 in the mitochondrial genome. Results
      presented here demonstrate that ORF239 causes pollen disruption in transgenic
      tobacco plants and may do so without targeting of the protein to the
      mitochondrion.

PMID- 8876212
TI  - Multiple paternity in two natural populations (orchard and vineyard) of
      Drosophila.
AB  - Male mating success is an important fitness component in Drosophila. The seminal
      fluid conveyed with the sperm inhibits the proclivity of the female to remate and
      reduces her fitness. Nevertheless, females may remate before they have exhausted
      the sperm from the first male and consequently use sperm from both males. We have
      studied concurrent multiple paternity (CMP) in two Drosophila melanogaster
      populations, from an apple orchard and a vineyard just after harvest. CMP is high
      in both populations, somewhat greater than 50%; but it is not significantly
      higher in the vineyard, where the population density is much greater than in the
      orchard. Population density had been thought to be an important determinant of
      CMP incidence. We have used four gene loci coding for enzymes as independent
      markers for detecting CMP.

PMID- 8876213
TI  - T-cell alpha beta + and gamma delta + deficient mice display abnormal but
      distinct phenotypes toward a natural, widespread infection of the intestinal
      epithelium.
AB  - Vertebrate immune systems contain T cells bearing either alpha beta or gamma
      delta T-cell antigen receptors (TCRs). alpha beta T cells perform all well
      characterized T-cell effector functions, while the biological functions of gamma
      delta + cells remain unclear. Of particular interest is the role of gamma delta +
      cells during epithelial infections, since gamma delta + cells are commonly
      abundant within epithelia. Eimeria spp. are intracellular protozoa that infect
      epithelia of most vertebrates, causing coccidiosis. This study shows that in
      response to Eimeria vermiformis, mice lacking alpha beta T cells display defects
      in protective immunity, while mice lacking gamma delta + cells display
      exaggerated intestinal damage, apparently due to a failure to regulate the
      consequences of the alpha beta T cell response. An immuno-downregulatory role
      during infection, and during autoimmune disease, may be a general one for gamma
      delta + cells.

PMID- 8876214
TI  - Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and
      differentiation.
AB  - Herein we describe the molecular characterization of the human leukocyte
      activation antigen CD100 and identify it as the first semaphorin, to our
      knowledge, in the immune system. Semaphorins have recently been described as
      neuronal chemorepellants that direct pioneering neurons during nervous system
      development. In this study we demonstrate that CD100 induces B cells to aggregate
      and improves their viability in vitro. We show that CD100 modifies CD40-CD40L B
      cell signaling by augmenting B-cell aggregation and survival and down-regulating
      CD23 expression. Thus, these results suggest that semaphorins as exemplified by
      CD100 also play a functional role in the immune system.

PMID- 8876215
TI  - Major histocompatibility class I presentation of soluble antigen facilitated by
      Mycobacterium tuberculosis infection.
AB  - Cell-mediated immune responses are essential for protection against many
      intracellular pathogens. For Mycobacterium tuberculosis (MTB), protection
      requires the activity of T cells that recognize antigens presented in the context
      of both major histocompatibility complex (MHC) class II and I molecules. Since
      MHC class I presentation generally requires antigen to be localized to the
      cytoplasmic compartment of antigen-presenting cells, it remains unclear how
      pathogens that reside primarily within endocytic vesicles of infected
      macrophages, such as MTB, can elicit specific MHC class I-restricted T cells. A
      mechanism is described for virulent MTB that allows soluble antigens ordinarily
      unable to enter the cytoplasm, such as ovalbumin, to be presented through the MHC
      class I pathway to T cells. The mechanism is selective for MHC class I
      presentation, since MTB infection inhibited MHC class II presentation of
      ovalbumin. The MHC class I presentation requires the tubercle bacilli to be
      viable, and it is dependent upon the transporter associated with antigen
      processing (TAP), which translocates antigenic peptides from the cytoplasm into
      the endoplasmic reticulum. The process is mimicked by Listeria monocytogenes and
      soluble listeriolysin, a pore-forming hemolysin derived from it, suggesting that
      virulent MTB may have evolved a comparable mechanism that allows molecules in a
      vacuolar compartment to enter the cytoplasmic presentation pathway for the
      generation of protective MHC class I-restricted T cells.

PMID- 8876216
TI  - The natural killer cell receptor Ly-49A recognizes a peptide-induced
      conformational determinant on its major histocompatibility complex class I
      ligand.
AB  - Natural killer (NK) cells are inhibited from killing cellular targets by major
      histocompatibility complex (MHC) class I molecules. In the mouse, this can be
      mediated by the Ly-49A NK cell receptor that specifically binds the H-2Dd MHC
      class I molecule, then inhibits NK cell activity. Previous experiments have
      indicated that Ly-49A recognizes the alpha 1/alpha 2 domains of MHC class I and
      that no specific MHC-bound peptide appeared to be involved. We demonstrate here
      that alanine-substituted peptides, having only the minimal anchor motifs,
      stabilized H-2Dd expression and provided resistance to H-2Dd-transfected,
      transporter associated with processing (TAP)-deficient cells from lysis by Ly
      49A+ NK cells. Peptide-induced resistance was blocked only by an mAb that binds a
      conformational determinant on H-2Dd. Moreover, stabilization of "empty" H-2Dd
      heavy chains by exogenous beta 2-microglobulin did not confer resistance. In
      contrast to data for MHC class I-restricted T cells that are specific for
      peptides displayed MHC molecules, these data indicate that NK cells are specific
      for a peptide-induced conformational determinant, independent of specific
      peptide. This fundamental distinction between NK cells and T cells further
      implies that NK cells are sensitive only to global changes in MHC class I
      conformation or expression, rather than to specific pathogen-encoded peptides.
      This is consistent with the "missing self" hypothesis, which postulates that NK
      cells survey tissues for normal expression of MHC class I.

PMID- 8876217
TI  - Effect of interleukin 12 on tumor induction by 3-methylcholanthrene.
AB  - Interleukin (IL)-12 has strong antitumor activity in transplantable tumor systems
      in the mouse. The present study was designed to determine whether tumor induction
      by 3-methylcholanthrene (3-MC), a carcinogenic hydrocarbon, can be inhibited by
      IL-12. BALB/cBy mice were injected subcutaneously with 25 micrograms or 100
      micrograms of 3-MC and treated with 100 ng, 10 ng, or 1 ng of IL-12 for 5 days a
      week for 18 weeks, with a schedule of 3 weeks on and 1 week off. In mice injected
      with 25 micrograms of 3-MC, treatment with 100 ng of IL-12 delayed tumor
      appearance and reduced tumor incidence. Tumor appearance was also delayed in mice
      injected with 100 micrograms of 3-MC and treated with 100 ng of IL-12, but the
      final tumor incidence was the same as in non-IL-12-treated mice. In contrast to
      the characteristically round, hard, well-circumscribed, and protruding tumor
      induced by 3-MC, a percentage of tumors induced in IL-12-treated mice had
      atypical characteristics: flat, soft, and invasive. Atypical tumors had a longer
      latent period and were more frequently seen in mice injected with 100 micrograms
      of 3-MC and treated with 100 ng of IL-12. Interferon gamma, IL-10, and tumor
      necrosis factor could be induced throughout the treatment period by IL-12,
      indicating that repeated injections of IL-12 do not induce a state of
      tachyphylaxis. High production of interferon gamma by CD8 T cells and a TH2-->TH1
      or TH0 shift in the cytokine secretion profile of CD4 T cells were also seen in
      the IL-12-treated mice. IL-12 provides a powerful new way to explore the
      defensive role of the immune system in tumorigenesis.

PMID- 8876218
TI  - Human prostate tumor growth in athymic mice: inhibition by androgens and
      stimulation by finasteride.
AB  - When the human prostate cancer cell line, LNCaP 104-S, the growth of which is
      stimulated by physiological levels of androgen, is cultured in androgen-depleted
      medium for > 100 passages, the cells, now called LNCaP 104-R2, are
      proliferatively repressed by low concentrations of androgens. LNCaP 104-R2 cells
      formed tumors in castrated male athymic nude mice. Testosterone propionate (TP)
      treatment prevented LNCaP 104-R2 tumor growth and caused regression of
      established tumors in these mice. Such a tumor-suppressive effect was not
      observed with tumors derived from LNCaP 104-S cells or androgen receptor-negative
      human prostate cancer PC-3 cells. 5 alpha-Dihydrotestosterone, but not 5 beta
      dihydrotestosterone, 17 beta-estradiol, or medroxyprogesterone acetate, also
      inhibited LNCaP 104-R2 tumor growth. Removal of TP or implantation of
      finasteride, a 5 alpha-reductase inhibitor, in nude mice bearing TP implants
      resulted in the regrowth of LNCaP 104-R2 tumors. Within 1 week after TP
      implantation, LNCaP 104-R2 tumors exhibited massive necrosis with severe
      hemorrhage. Three weeks later, these tumors showed fibrosis with infiltration of
      chronic inflammatory cells and scattered carcinoma cells exhibiting degeneration.
      TP treatment of mice with LNCaP 104-R2 tumors reduced tumor androgen receptor and
      c-myc mRNA levels but increased prostate-specific antigen in serum- and prostate
      specific antigen mRNA in tumors. Although androgen ablation has been the standard
      treatment for metastatic prostate cancer for > 50 years, our study shows that
      androgen supplementation therapy may be beneficial for treatment of certain types
      of human prostate cancer and that the use of 5 alpha-reductase inhibitors, such
      as finasteride or anti-androgens, in the general treatment of metastatic prostate
      cancer may require careful assessment.

PMID- 8876220
TI  - Studies on locus content mapping.
AB  - Locus content maps are derived from monosomic or disomic chromosomes broken by
      radiation, shearing, or other clastogen, the fragments being distributed among
      clones by dilution or incorporation into the cells of another species and scored
      for segregation of markers. Locus content maps provide evidence about
      radiosensitivity of chromosome regions, support for order, and approximate
      location. Omission of the most aberrant and least informative clones increases
      efficiency of localization. Correct analysis must allow for preferential
      retention of certain sequences, monosomy or polysomy of donor chromosomes, and
      error filtration. Combination of these refinements extracts substantially more
      information from fewer clones. Because of unmodeled peculiarities in the data,
      the best analysis does not recover the physical map but roughly localizes markers
      that may be monomorphic and therefore unsuitable for linkage mapping. As with
      linkage for polymorphic loci, distance in the composite map should be confirmed
      by physical methods.

PMID- 8876219
TI  - Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial
      cell adhesion molecule 1.
AB  - Platelet-endothelial cell adhesion molecule 1 (PECAM-1, CD31) is a 130-kDa member
      of the immunoglobulin gene superfamily expressed on endothelial cells, platelets,
      neutrophils, and monocytes and plays a role during endothelial cell migration.
      Phosphoamino acid analysis and Western blot analysis with anti-phosphotyrosine
      antibody show that endothelial PECAM-1 is tyrosine-phosphorylated.
      Phosphorylation is decreased with endothelial cell migration on fibronectin and
      collagen and with cell spreading on fibronectin but not on plastic. Cell adhesion
      on anti-integrin antibodies is also able to specifically induce PECAM-1
      dephosphorylation while concurrently inducing pp125 focal adhesion kinase
      phosphorylation. Inhibition of dephosphorylation with sodium orthovanadate
      suggests that this effect is at least partially mediated by phosphatase activity.
      Tyr-663 and Tyr-686 are identified as potential phosphorylation sites and mutated
      to phenylalanine. When expressed, both mutants show reduced PECAM-1
      phosphorylation but Phe-686 mutants also show significant reversal of PECAM-1
      mediated inhibition of cell migration and do not localize PECAM-1 to cell
      borders. Our results suggest that beta 1-integrin engagement can signal to
      dephosphorylate PECAM-1 and that this signaling pathway may play a role during
      endothelial cell migration.

PMID- 8876221
TI  - Identification of a functionally important sequence in the cytoplasmic tail of
      integrin beta 3 by using cell-permeable peptide analogs.
AB  - Integrins are major two-way signaling receptors responsible for the attachment of
      cells to the extracellular matrix and for cell-cell interactions that underlie
      immune responses, tumor metastasis, and progression of atherosclerosis and
      thrombosis. We report the structure-function analysis of the cytoplasmic tail of
      integrin beta 3 (glycoprotein IIla) based on the cellular import of synthetic
      peptide analogs of this region. Among the four overlapping cell-permeable
      peptides, only the peptide carrying residues 747-762 of the carboxyl-terminal
      segment of integrin beta 3 inhibited adhesion of human erythroleukemia (HEL)
      cells and of human endothelial cells (ECV) 304 to immobilized fibrinogen mediated
      by integrin beta 3 heterodimers, alpha IIb beta 3, and alpha v beta 3,
      respectively. Inhibition of adhesion was integrin-specific because the cell
      permeable beta 3 peptide (residues 747-762) did not inhibit adhesion of human
      fibroblasts mediated by integrin beta 1 heterodimers. Conversely, a cell
      permeable peptide representing homologous portion of the integrin beta 1
      cytoplasmic tail (residues 788-803) inhibited adhesion of human fibroblasts,
      whereas it was without effect on adhesion of HEL or ECV 304 cells. The cell
      permeable integrin beta 3 peptide (residues 747-762) carrying a known loss-of
      function mutation (Ser752Pro) responsible for the genetic disorder Glanzmann
      thrombasthenia Paris I did not inhibit cell adhesion of HEL or ECV 304 cells,
      whereas the beta 3 peptide carrying a Ser752Ala mutation was inhibitory. Although
      Ser752 is not essential, Tyr747 and Tyr759 form a functionally active tandem
      because conservative mutations Tyr747Phe or Tyr759Phe resulted in a nonfunctional
      cell permeable integrin beta 3 peptide. We propose that the carboxyl-terminal
      segment of the integrin beta 3 cytoplasmic tail spanning residues 747-762
      constitutes a major intracellular cell adhesion regulatory domain (CARD) that
      modulates the interaction of integrin beta 3-expressing cells with immobilized
      fibrinogen. Import of cell-permeable peptides carrying this domain results in
      inhibition "from within" of the adhesive function of these integrins.

PMID- 8876222
TI  - G protein-coupled cholecystokinin-B/gastrin receptors are responsible for
      physiological cell growth of the stomach mucosa in vivo.
AB  - Many peptide hormone and neurotransmitter receptors belonging to the seven
      membrane-spanning G protein-coupled receptor family have been shown to transmit
      ligand-dependent mitogenic signals in vitro. However, the physiological roles of
      the mitogenic activity through G protein-coupled receptors in vivo remain to be
      elucidated. Here we have generated G protein-coupled cholecystokinin (CCK)
      B/gastrin receptor deficient-mice by gene targeting. The homozygous mice showed a
      remarkable atrophy of the gastric mucosa macroscopically, even in the presence of
      severe hypergastrinemia. The atrophy was due to a decrease in parietal cells and
      chromogranin A-positive enterochromaffin-like cells expressing the H+,K(+)-ATPase
      and histidine decarboxylase genes, respectively. Oral administration of a proton
      pump inhibitor, omeprazole, which induced hypertrophy of the gastric mucosa with
      hypergastrinemia in wild-type littermates, did not eliminate the gastric atrophy
      of the homozygotes. These results clearly demonstrated that the G protein-coupled
      CCK-B/gastrin receptor is essential for the physiological as well as pathological
      proliferation of gastric mucosal cells in vivo.

PMID- 8876223
TI  - Transcription factor EGR-1 suppresses the growth and transformation of human HT
      1080 fibrosarcoma cells by induction of transforming growth factor beta 1.
AB  - The early growth response 1 (EGR-1) gene product is a transcription factor with
      role in differentiation and growth. We have previously shown that expression of
      exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces
      growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1
      expression by antisense RNA eliminates protein expression, enhances growth, and
      promotes phenotypic transformation. However, the mechanism of these effects
      remained unknown. The promoter of human transforming growth factor beta 1 (TGF
      beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR
      1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically
      active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1
      expressed and addition of recombinant human TGF-beta 1 is strongly growth
      suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to
      EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects
      of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1
      promoter was activated 4- to 6-fold relative to a control reporter in either HT
      1080 cells that stably expressed or parental cells cotransfected with an EGR-1
      expression vector. Expression of delta EGR-1, a mutant that cannot interact with
      the corepressors, nerve growth factor-activated factor binding proteins NAB1 and
      NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation
      of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter
      construct reflected the appropriate in vivo regulatory context. The EGR-1
      stimulated transactivation was inhibited by expression of the Wilms tumor
      suppressor, a known specific DNA-binding competitor. These results indicate that
      EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF
      beta 1.

PMID- 8876224
TI  - Molecular cytogenetic delineation of a novel critical genomic region in
      chromosome bands 11q22.3-923.1 in lymphoproliferative disorders.
AB  - Aberrations of the long arm of chromosome 11 are among the most common chromosome
      abnormalities in lymphoproliferative disorders (LPD). Translocations involving
      BCL1 at 11q13 are strongly associated with mantle cell lymphoma. other nonrandom
      aberrations, especially deletions and, less frequently, translocations, involving
      bands 11q21-923 have been identified by chromosome banding analysis. To date, the
      critical genomic segment and candidate genes involved in these deletions have not
      been identified. In the present study, we have analyzed tumors from 43 patients
      with LPD (B-cell chronic lymphocytic leukemia, n = 40; mantle cell lymphoma, n =
      3) showing aberrations of bands 11q21-923 by fluorescence in situ hybridization.
      As probes we used Alu-PCR products from 17 yeast artificial chromosome clones
      spanning chromosome bands 11q14.3-923.3, including a panel of yeast artificial
      chromosome clones recognizing a contiguous genomic DNA fragment of approximately
      9-10 Mb in bands 11q22.3-923.3. In the 41 tumors exhibiting deletions, we
      identified a commonly deleted segment in band 11q22.3-923.1; this region is
      approximately 2-3 Mb in size and contains the genes coding for ATM (ataxia
      telangiectasia mutated), RDX (radixin), and FDX1 (ferredoxin 1). Furthermore, two
      translocation break-points were localized to a 1.8-Mb genomic fragment contained
      within the commonly deleted segment. Thus, we have identified a single critical
      region of 2-3 Mb in size in which 11q14-923 aberrations in LPD cluster. This
      provides the basis for the identification of the gene(s) at 11q22.3-923.1 that
      are involved in the pathogenesis of LPD.

PMID- 8876225
TI  - Efficient infection of a human T-cell line and of human primary peripheral blood
      leukocytes with a pseudotyped retrovirus vector.
AB  - Peripheral blood lymphocytes (PBLs) are an important target for gene transfer
      studies aimed at human gene therapy. However, no reproducibly efficient methods
      are currently available to transfer foreign, potentially therapeutic genes into
      these cells. While vectors derived from murine retroviruses have been the most
      widely used system, their low infection efficiency in lymphocytes has required
      prolonged in vitro culturing and selection after infection to obtain useful
      numbers of genetically modified cells. We previously reported that retroviral
      vectors pseudotyped with vesicular stomatitis G glycoprotein (VSV-G) envelope can
      infect a wide variety of cell types and can be concentrated to titers of greater
      than 10(9) infectious units/ml. In this present study, we examined the ability of
      amphotropic and pseudotyped vectors expressing a murine cell surface protein, B7
      1, to infect the human T-cell line Jurkat or human blood lymphocytes. Limiting
      dilution analysis of transduced Jurkat cells demonstrated that the pseudotyped
      vector is significantly more efficient in infecting T cells than an amphotropic
      vector used at the same multiplicity of infection (moi). To identify the
      transduction efficiency on PBLs, we examined the levels of cell surface
      expression of the B7-1 surface marker 48 to 72 hr after infection. The
      transduction efficiency of PBLs with the pseudotyped vector increased linearly
      with increasing moi to a maximum of approximately 16-32% at an moi of 40. This
      relatively high efficiency of infection of a T-cell line and of blood lymphocytes
      with VSV-G pseudotyped virus demonstrates that such modified pseudotyped
      retrovirus vectors may be useful reagents for studies of gene therapy for a
      variety of genetic or neoplastic disorders.

PMID- 8876226
TI  - Reactive oxygen species are downstream mediators of p53-dependent apoptosis.
AB  - Reactive oxygen species (ROS) have been implicated as potential modulators of
      apoptosis. Conversely, experiments under hypoxic conditions have suggested that
      apoptosis could occur in the absence of ROS. We sought to determine whether a
      central modulator of apoptosis, p53, regulates the levels of intracellular ROS
      and whether a rise in ROS levels is required for the induction of p53-dependent
      apoptosis. We transiently overexpressed wild-type p53, using adenoviral gene
      transfer, and identified cell types that were sensitive or resistant to p53
      mediated apoptosis. Cells sensitive to p53-mediated apoptosis produced ROS
      concomitantly with p53 overexpression, whereas cells resistant to p53 failed to
      produce ROS. In sensitive cells, both ROS production and apoptosis were inhibited
      by antioxidant treatment. These results suggest that p53 acts to regulate the
      intracellular redox state and induces apoptosis by a pathway that is dependent on
      ROS production.

PMID- 8876227
TI  - Nitration and inactivation of manganese superoxide dismutase in chronic rejection
      of human renal allografts.
AB  - Inflammatory processes in chronic rejection remain a serious clinical problem in
      organ transplantation. Activated cellular infiltrate produces high levels of both
      superoxide and nitric oxide. These reactive oxygen species interact to form
      peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine.
      We identified enhanced immunostaining for nitrotyrosine localized to tubular
      epithelium of chronically rejected human renal allografts. Western blot analysis
      of rejected tissue demonstrated that tyrosine nitration was restricted to a few
      specific polypeptides. Immunoprecipitation and amino acid sequencing techniques
      identified manganese superoxide dismutase, the major antioxidant enzyme in
      mitochondria, as one of the targets of tyrosine nitration. Total manganese
      superoxide dismutase protein was increased in rejected kidney, particularly in
      the tubular epithelium; however, enzymatic activity was significantly decreased.
      Exposure of recombinant human manganese superoxide dismutase to peroxynitrite
      resulted in a dose-dependent (IC50 = 10 microM) decrease in enzymatic activity
      and concomitant increase in tyrosine nitration. Collectively, these observations
      suggest a role for peroxynitrite during development and progression of chronic
      rejection in human renal allografts. In addition, inactivation of manganese
      superoxide dismutase by peroxynitrite may represent a general mechanism that
      progressively increases the production of peroxynitrite, leading to irreversible
      oxidative injury to mitochondria.

PMID- 8876228
TI  - Critical role of reverse transcriptase in the inhibitory mechanism of CNI-H0294
      on HIV-1 nuclear translocation.
AB  - HIV-1 replication requires the translocation of viral genome into the nucleus of
      a target cell. We recently reported the synthesis of an arylene bis(methyl
      ketone) compound (CNI-H0294) that inhibits nuclear targeting of the HIV-1 genome
      and thus HIV-1 replication in monocyte cultures. Here we demonstrate that CNI
      H0294 inhibits nuclear targeting of HIV-1-derived preintegration complexes by
      inactivating the nuclear localization sequence of the HIV-1 matrix antigen in a
      reaction that absolutely requires reverse transcriptase. This drug/reverse
      transcriptase interaction defines the specificity of its antiviral effect and is
      most likely mediated by the pyrimidine side-chain of CNI-H0294. After binding to
      reverse transcriptase, the carbonyl groups of CNI-H0294 react with the nuclear
      localization sequence of matrix antigen and prevent its binding to karyopherin
      alpha, the cellular receptor for nuclear localization sequences that carries
      proteins into the nucleus. Our results provide a basis for the development of a
      novel class of compounds that inhibit nuclear translocation and that can, in
      principle, be modified to target specific infectious agents.

PMID- 8876229
TI  - On the molecular mechanism of chloroquine's antimalarial action.
AB  - Chloroquine is thought to exert its antimalarial effect by preventing the
      polymerization of toxic heme released during proteolysis of hemoglobin in the
      Plasmodium digestive vacuole. The mechanism of this blockade has not been
      established. We incubated cultured parasites with subinhibitory doses of
      [3H]chloroquine and [3H] quinidine. These [3H]quinoline compounds became
      associated with hemozoin as assessed by electron microscope autoradiography and
      subcellular fractionation. In vitro, binding of [3H]quinoline inhibitors to the
      hemozoin chain depended on the addition of heme substrate. These data counter
      previous conclusions regarding the lack of quinoline association with hemozoin,
      explain the exaggerated accumulation of quinolines in the plasmodium digestive
      vacuole, and suggest that a quinoline heme complex incorporates into the growing
      polymer to terminate chain extension, blocking further sequestration of toxic
      heme.

PMID- 8876230
TI  - Improved retroviral gene transfer into murine and Rhesus peripheral blood or bone
      marrow repopulating cells primed in vivo with stem cell factor and granulocyte
      colony-stimulating factor.
AB  - In previous studies we showed that 5 days of treatment with granulocyte colony
      stimulating factor (G-CSF) and stem cell factor (SCF) mobilized murine
      repopulating cells to the peripheral blood (PB) and that these cells could be
      efficiently transduced with retroviral vectors. We also found that, 7-14 days
      after cytokine treatment, the repopulating ability of murine bone marrow (BM)
      increased 10-fold. In this study we examined the efficiency of gene transfer into
      cytokine-primed murine BM cells and extended our observations to a nonhuman
      primate autologous transplantation model. G-CSF/SCF-primed murine BM cells
      collected 7-14 days after cytokine treatment were equivalent to post-5
      fluorouracil BM or G-CSF/SCF-mobilized PB cells as targets for retroviral gene
      transfer. In nonhuman primates, CD34-enriched PB cells collected after 5 days of
      G-CSF/SCF treatment and CD34-enriched BM cells collected 14 days later were
      superior targets for retroviral gene transfer. When a clinically approved
      supernatant infection protocol with low-titer vector preparations was used,
      monkeys had up to 5% of circulating cells containing the vector for up to a year
      after transplantation. This relatively high level of gene transfer was confirmed
      by Southern blot analysis. Engraftment after transplantation using primed BM
      cells was more rapid than that using steady-state bone marrow, and the fraction
      of BM cells saving the most primitive CD34+/CD38- or CD34+/CD38dim phenotype
      increased 3-fold. We conclude that cytokine priming with G-CSF/SCF may allow
      collection of increased numbers of primitive cells from both the PB and BM that
      have improved susceptibility to retroviral transduction, with many potential
      applications in hematopoietic stem cell-directed gene therapy.

PMID- 8876231
TI  - In vivo tracking of platelets: circulating degranulated platelets rapidly lose
      surface P-selectin but continue to circulate and function.
AB  - To examine the hypothesis that surface P-selectin-positive (degranulated)
      platelets are rapidly cleared from the circulation, we developed novel methods
      for tracking of platelets and measurement of platelet function in vivo. Washed
      platelets prepared from nonhuman primates (baboons) were labeled with PKH2 (a
      lipophilic fluorescent dye), thrombin-activated, washed, and reinfused into the
      same baboons. Three-color whole blood flow cytometry was used to simultaneously
      (i) identify platelets with a mAb directed against glycoprotein (GP)IIb-IIIa
      (integrin alpha 11b beta 3), (ii) distinguish infused platelets by their PKH2
      fluorescence, and (iii) analyze platelet function with mAbs. Two hours after
      infusion of autologous thrombin-activated platelets (P-selectin-positive, PKH2
      labeled), 95 +/- 1% (mean +/- SEM, n = 5) of the circulating PKH2-labeled
      platelets had become P-selectin-negative. Compared with platelets not activated
      with thrombin preinfusion, the recovery of these circulating PKH2-labeled, P
      selectin-negative platelets was similar 24 h after infusion and only slightly
      less 48 h after infusion. The loss of platelet surface P-selectin was fully
      accounted for by a 67.1 +/- 16.7 ng/ml increase in the plasma concentration of
      soluble P-selectin. The circulating PKH2-labeled, P-selectin-negative platelets
      were still able to function in vivo, as determined by their (i) participation in
      platelet aggregates emerging from a bleeding time wound, (ii) binding to Dacron
      in an arteriovenous shunt, (iii) binding of mAb PAC1 (directed against the
      fibrinogen binding site on GPIIb-IIIa), and (iv) generation of procoagulant
      platelet-derived microparticles. In summary, (i) circulating degranulated
      platelets rapidly lose surface P-selectin to the plasma pool, but continue to
      circulate and function; and (ii) we have developed novel three-color whole blood
      flow cytometric methods for tracking of platelets and measurement of platelet
      function in vivo.

PMID- 8876232
TI  - Polyadenylylated nuclear RNA encoded by Kaposi sarcoma-associated herpesvirus.
AB  - A newly recognized gamma herpesvirus known as Kaposi sarcoma-associated
      herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is present in Kaposi sarcomas
      and body-cavity-based lymphomas. Here we identify a novel abundant 1.2-kb RNA,
      polyadenylated nuclear RNA (PAN RNA), encoded by the virus. The majority of cDNAs
      produced from poly(A)-selected RNA isolated from a human body cavity lymphoma
      cell line 48 hr after butyrate induction of KSHV lytic replication represented
      PAN RNA. Within PAN RNA were two 9 and 16 nt stretches with 89% and 94% identity
      to U1 RNA. A third stretch of 14 nt was 93% complementary to U1. The 5' upstream
      region of PAN RNA contained both proximal and distal sequence elements
      characteristic of regulatory regions of U snRNAs, whereas the 3' end was
      polyadenylylated. PAN RNA was transcribed by RNA polymerase II, lacked a
      trimethylguanosine cap, and did not associate with polyribosomes. PAN RNA formed
      a speckled pattern in the nucleus typical of U snRNAs and colocalized with Sm
      protein. Therefore, PAN represents a new type of RNA, possessing features of both
      U snRNA and mRNA.

PMID- 8876233
TI  - Comparison of circumsporozoite proteins from avian and mammalian malarias:
      biological and phylogenetic implications.
AB  - The circumsporozoite (CS) protein of malaria parasites (Plasmodium) covers the
      surface of sporozoites that invade hepatocytes in mammalian hosts and macrophages
      in avian hosts. CS genes have been characterized from many Plasmodium that infect
      mammals; two domains of the corresponding proteins, identified initially by their
      conservation (region I and region II), have been implicated in binding to
      hepatocytes. The CS gene from the avian parasite Plasmodium gallinaceum was
      characterized to compare these functional domains to those of mammalian
      Plasmodium and for the study of Plasmodium evolution. The P. gallinaceum protein
      has the characteristics of CS proteins, including a secretory signal sequence,
      central repeat region, regions of charged amino acids, and an anchor sequence.
      Comparison with CS signal sequences reveals four distinct groupings, with P.
      gallinaceum most closely related to the human malaria Plasmodium falciparum. The
      5-amino acid sequence designated region I, which is identical in all mammalian CS
      and implicated in hepatocyte invasion, is different in the avian protein. The P.
      gallinaceum repeat region consists of 9-amino acid repeats with the consensus
      sequence QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which
      is associated with targeting the invasion of liver cells, is also conserved in
      the avian protein. Phylogenetic analysis of the aligned Plasmodium CS sequences
      yields a tree with a topology similar to the one obtained using sequence data
      from the small subunit rRNA gene. The phylogeny using the CS gene supports the
      proposal that the human malaria P. falciparum is significantly more related to
      avian parasites than to other parasites infecting mammals, although the biology
      of sporozoite invasion is different between the avian and mammalian species.

PMID- 8876234
TI  - Synergistic up-regulation of the myeloid-specific promoter for the macrophage
      colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may
      contribute to leukemogenesis.
AB  - AML1 is involved in the (8;21) translocation, associated with acute myelogenous
      leukemia (AML)-type M2, which results in the production of the AML1-ETO fusion
      protein: the amino-terminal 177 amino acids of AML1 and the carboxyl-terminal 575
      amino acids of ETO. The mechanism by which AML1-ETO accomplishes leukemic
      transformation is unknown; however, AML1-ETO interferes with AML1 transactivation
      of such AML1 targets as the T-cell receptor beta enhancer and the granulocyte
      macrophage colony-stimulating factor promoter. Herein, we explored the effect of
      AML1-ETO on regulation of a myeloid-specific AML1 target, the macrophage colony
      stimulating factor (M-CSF) receptor promoter. We found that AML1-ETO and AML1
      work synergistically to transactivate the M-CSF receptor promoter, thus
      exhibiting a different activity than previously described. Truncation mutants
      within the ETO portion of AML1-ETO revealed the region of ETO necessary for the
      cooperativity between AML1 and AML1-ETO lies between amino acids 347 and 540.
      Endogenous M-CSF receptor expression was examined in Kasumi-1 cells, derived from
      a patient with AML-M2 t(8;21) and the promonocytic cell line U937. Kasumi-1 cells
      exhibited a significantly higher level of M-CSF receptor expression than U937
      cells. Bone marrow from patients with AML-M2 t(8;21) also exhibited a higher
      level of expression of M-CSF receptor compared with normal controls. The
      upregulation of M-CSF receptor expression by AML1-ETO may contribute to the
      development of a leukemic state in these patients.

PMID- 8876235
TI  - A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter
      is a heterodimer of two half ATP-binding cassette transporters.
AB  - The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane
      protein (PMP70) are half ATP-binding cassette (ABC) transporters in the human
      peroxisome membrane. ALDP and PMP70 share sequence homology and both are
      implicated in genetic diseases. PXA1 and YKL741 are Saccharomyces cerevisiae
      genes that encode homologs of ALDP and PMP70. Pxa1p, a putative ortholog of ALDP,
      is involved in peroxisomal beta-oxidation of fatty acids while YKL741 is an open
      reading frame found by the yeast genome sequencing project. Here we designate
      YKL741 as PXA2 and show that its protein product, Pxa2p, like Pxa1p, is
      associated with peroxisomes but not required for their assembly. Yeast strains
      carrying gene disruption of PXA1, PXA2, or both have similar and, in the case of
      the latter, nonadditive phenotypes. We also find that the stability of Pxa1p, but
      not Pxa2p, is markedly reduced in the absence of the other. Finally, we find that
      Pxa1p and Pxa2p coimmuno-precipitate. These genetic and physical data suggest
      that Pxa1p and Pxa2p heterodimerize to form a complete peroxisomal ABC
      transporter involved in fatty acid beta-oxidation. This result predicts the
      presence of similar heterodimeric ABC transporters in the mammalian peroxisome
      membrane.

PMID- 8876236
TI  - A novel clade of protistan parasites near the animal-fungal divergence.
AB  - Sequences of nuclear-encoded small-subunit rRNA genes have been determined for
      representatives of the enigmatic genera Dermocystidium, Ichthyophonus, and
      Psorospermium, protistan parasites of fish and crustaceans. The small-subunit
      rRNA genes from these parasites and from the "rosette agent" (also a parasite of
      fish) together form a novel, statistically supported clade. Phylogenetic analyses
      demonstrate this clade to diverge near the animal-fungal dichotomy, although more
      precise resolution is problematic. In the most parsimonious and maximally likely
      phylogenetic frameworks inferred from the most stably aligned sequence regions,
      the clade constitutes the most basal branch of the metazoa; but within a limited
      range of model parameters, and in some analyses that incorporate less well
      aligned sequence regions, an alternative topology in which it diverges
      immediately before the animal-fungal dichotomy was recovered. Mitochondrial
      cristae of Dermocystidium spp. are flat, whereas those of Ichthyophonus hoferi
      appear tubulovesiculate. These results extend our understanding of the types of
      organisms from which metazoa and fungi may have evolved.

PMID- 8876237
TI  - Haemophilus influenzae pili are composite structures assembled via the HifB
      chaperone.
AB  - Haemophilus influenzae is a Gram-negative bacterium that represents a common
      cause of human disease. Disease due to this organism begins with colonization of
      the upper respiratory mucosa, a process facilitated by adhesive fibers called
      pili. In the present study, we investigated the structure and assembly of H.
      influenzae pili. Examination of pili by electron microscopy using quick-freeze,
      deep-etch and immunogold techniques revealed the presence of two distinct
      subassemblies, including a flexible two-stranded helical rod comprised of HifA
      and a short, thin, distal tip structure containing HifD. Genetic and biochemical
      studies demonstrated that the biogenesis of H. influenzae pili is dependent on a
      periplasmic chaperone called HifB, which belongs to the PapD family of
      immunoglobulin-like chaperones. HifB bound directly to HifA and HifD, forming
      HifB-HifA and HifB-HifD complexes, which were purified from periplasmic extracts
      by ion-exchange chromatography. Continued investigation of the biogenesis of H.
      influenzae pili should provide general insights into organelle development and
      may suggest novel strategies for disease prevention.

PMID- 8876238
TI  - The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved
      in cell wall arabinan biosynthesis that is the target for the antimycobacterial
      drug ethambutol.
AB  - The antimycobacterial compound ethambutol [Emb; dextro-2,2'-(ethylenediimino)-di
      1-butanol] is used to treat tuberculosis as well as disseminated infections
      caused by Mycobacterium avium. The critical target for Emb lies in the pathway
      for the biosynthesis of cell wall arabinogalactan, but the molecular mechanisms
      for drug action and resistance are unknown. The cellular target for Emb was
      sought using drug resistance, via target overexpression by a plasmid vector, as a
      selection tool. This strategy led to the cloning of the M. avium emb region which
      rendered the otherwise susceptible Mycobacterium smegmatis host resistant to Emb.
      This region contains three complete open reading frames (ORFs), embR, embA, and
      embB. The translationally coupled embA and embB genes are necessary and
      sufficient for an Emb-resistant phenotype which depends on gene copy number, and
      their putative novel membrane proteins are homologous to each other. The
      predicted protein encoded by embR, which is related to known transcriptional
      activators from Streptomyces, is expendable for the phenotypic expression of Emb
      resistance, but an intact divergent promoter region between embR and embAB is
      required. An Emb-sensitive cell-free assay for arabinan biosynthesis shows that
      overexpression of embAB is associated with high-level Emb-resistant arabinosyl
      transferase activity, and that embR appears to modulate the in vitro level of
      this activity. These data suggest that embAB encode the drug target of Emb, the
      arabinosyl transferase responsible for the polymerization of arabinose into the
      arabinan of arabinogalactan, and that overproduction of this Emb-sensitive target
      leads to Emb resistance.

PMID- 8876239
TI  - The Drosophila Numb protein inhibits signaling of the Notch receptor during cell
      cell interaction in sensory organ lineage.
AB  - Specification of unequal daughter cell fates in the Drosophila external sense
      organ lineage requires asymmetric localization of the intrinsic determinant Numb
      as well as cell-cell interactions mediated by the Delta ligand and Notch
      receptor. Previous genetic studies indicated that numb acts upstream of Notch,
      and biochemical studies revealed that Numb can bind Notch. For a functional assay
      of the action of Numb on Notch signaling, we expressed these proteins in cultured
      Drosophila cells and used nuclear translocation of Suppressor of Hairless [Su(H)]
      as a reporter for Notch activity. We found that Numb interfered with the ability
      of Notch to cause nuclear translocation of Su(H); both the C-terminal half of the
      phosphotyrosine binding domain and the C terminus of Numb are required to inhibit
      Notch. Overexpression of Numb during wing development, which is sensitive to
      Notch dosage, revealed that Numb is also able to inhibit the Notch receptor in
      vivo. In the external sense organ lineage, the phosphotyrosine binding domain of
      Numb was found to be essential for the function but not for asymmetric
      localization of Numb. Our results suggest that Numb determines daughter cell
      fates in the external sense organ lineage by inhibiting Notch signaling.

PMID- 8876240
TI  - Regulation of striatal D1A dopamine receptor gene transcription by Brn-4.
AB  - Brn-4 is a member of the POU transcription factor family and is expressed in the
      central nervous system. In this study, we addressed whether Brn-4 regulates
      expression of the D1A dopamine receptor gene. We found a functional Brn-4
      responsive element in the intron of this gene by means of cotransfection
      chloramphenical acetyltransferase assays. This region contains two consensus
      sequences for binding of POU factors. Gel mobility-shift assays using glutathione
      S-transferase-Brn-4 fusion protein indicated that Brn-4 binds to these sequences.
      Both these sites are essential for transactivation by Brn-4 because deletion of
      either significantly reduced this enhancer activity. In situ hybridization
      revealed colocalization of Brn-4 and D1A mRNAs at the level of a single neuron in
      the rat striatum where this dopamine receptor is most abundantly expressed. Gel
      mobility-supershift assay using rat striatal nuclear extract and Brn-4 antibody
      confirmed the presence of Brn-4 in this brain region and its ability to bind to
      its consensus sequences in the D1A gene. These data suggest a functional role for
      Brn-4 in the expression of the D1A dopamine receptor gene both in vitro and in
      vivo.

PMID- 8876241
TI  - Differential synaptic localization of two major gamma-aminobutyric acid type A
      receptor alpha subunits on hippocampal pyramidal cells.
AB  - Hippocampal pyramidal cells, receiving domain specific GABAergic inputs, express
      up to 10 different subunits of the gamma-aminobutyric acid type A (GABAA)
      receptor, but only 3 different subunits are needed to form a functional
      pentameric channel. We have tested the hypothesis that some subunits are
      selectively located at subsets of GABAergic synapses. The alpha 1 subunit has
      been found in most GABAergic synapses on all postsynaptic domains of pyramidal
      cells. In contrast, the alpha 2 subunit was located only in a subset of synapses
      on the somata and dendrites, but in most synapses on axon initial segments
      innervated by axo-axonic cells. The results demonstrate that molecular
      specialization in the composition of postsynaptic GABAA receptor subunits
      parallels GABAergic cell specialization in targeting synapses to a specific
      domain of postsynaptic cortical neurons.

PMID- 8876242
TI  - Phosphorylation of synaptic vesicle proteins: modulation of the alpha SNAP
      interaction with the core complex.
AB  - We analyzed whether synaptic membrane trafficking proteins are substrates for
      casein kinase II, calcium/calmodulin-dependent protein kinase II, and cAMP
      dependent protein kinase (PKA), three kinases implicated in the modulation of
      synaptic transmission. Each kinase phosphorylates a specific set of the vesicle
      proteins syntaxin 1A, N-ethylmaleimide-sensitive factor (NSF), vesicle-associated
      membrane protein (VAMP), synaptosome-associated 25-kDa protein (SNAP-25), n-sec1,
      alpha soluble NSF attachment protein (alpha SNAP), and synaptotagmin. VAMP is
      phosphorylated by calcium/calmodulin-dependent protein kinase II on serine 61.
      alpha SNAP is phosphorylated by PKA; however, the beta SNAP isoform is
      phosphorylated only 20% as efficiently. alpha SNAP phosphorylated by PKA binds to
      the core docking and fusion complex 10 times weaker than the dephosphorylated
      form. These studies provide a first glimpse at regulatory events that may be
      important in modulating neurotransmitter release during learning and memory.

PMID- 8876243
TI  - Targeted deletion of the mouse POU domain gene Brn-3a causes selective loss of
      neurons in the brainstem and trigeminal ganglion, uncoordinated limb movement,
      and impaired suckling.
AB  - The Brn-3 subfamily of POU domain genes are expressed in sensory neurons and in
      select brainstem nuclei. Earlier work has shown that targeted deletion of the Brn
      3b and Brn-3c genes produce, respectively, defects in the retina and in the inner
      ear. We show herein that targeted deletion of the Brn-3a gene results in
      defective suckling and in uncoordinated limb and trunk movements, leading to
      early postnatal death. Brn-3a (-/-) mice show a loss of neurons in the trigeminal
      ganglia, the medial habenula, the red nucleus, and the caudal region of the
      inferior olivary nucleus but not in the retina and dorsal root ganglia. In the
      trigeminal and dorsal root ganglia, but not in the retina, there is a marked
      decrease in the frequency of neurons expressing Brn-3b and Brn-3c, suggesting
      that Brn-3a positively regulates Brn-3b and Brn-3c expression in somatosensory
      neurons. Thus, Brn-3a exerts its major developmental effects in somatosensory
      neurons and in brainstem nuclei involved in motor control. The pheno-types of Brn
      3a, Brn-3b, and Brn-3c mutant mice indicate that individual Brn-3 genes have
      evolved to control development in the auditory, visual, or somatosensory systems
      and that despite differences between these systems in transduction mechanisms,
      sensory organ structures, and central information processing, there may be
      fundamental homologies in the genetic regulatory events that control their
      development.

PMID- 8876244
TI  - A model of multiplicative neural responses in parietal cortex.
AB  - Visual responses of neurons in parietal area 7a are modulated by a combined eye
      and head position signal in a multiplicative manner. Neurons with multiplicative
      responses can act as powerful computational elements in neural networks. In the
      case of parietal cortex, multiplicative gain modulation appears to play a crucial
      role in the transformation of object locations from retinal to body-centered
      coordinates. It has proven difficult to uncover single-neuron mechanisms that
      account for neuronal multiplication. Here we show that multiplicative responses
      can arise in a network model through population effects. Specifically, neurons in
      a recurrently connected network with excitatory connections between similarly
      tuned neurons and inhibitory connections between differently tuned neurons can
      perform a product operation on additive synaptic inputs. The results suggest that
      parietal responses may be based on this architecture.

PMID- 8876245
TI  - Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and
      mismatch negativity generation: implications for schizophrenia.
AB  - Working memory refers to the ability of the brain to store and manipulate
      information over brief time periods, ranging from seconds to minutes. As opposed
      to long-term memory, which is critically dependent upon hippocampal processing,
      critical substrates for working memory are distributed in a modality-specific
      fashion throughout cortex. N-methyl-D-aspartate (NMDA) receptors play a crucial
      role in the initiation of long-term memory. Neurochemical mechanisms underlying
      the transient memory storage required for working memory, however, remain
      obscure. Auditory sensory memory, which refers to the ability of the brain to
      retain transient representations of the physical features (e.g., pitch) of simple
      auditory stimuli for periods of up to approximately 30 sec, represents one of the
      simplest components of the brain working memory system. Functioning of the
      auditory sensory memory system is indexed by the generation of a well-defined
      event-related potential, termed mismatch negativity (MMN). MMN can thus be used
      as an objective index of auditory sensory memory functioning and a probe for
      investigating underlying neurochemical mechanisms. Monkeys generate cortical
      activity in response to deviant stimuli that closely resembles human MMN. This
      study uses a combination of intracortical recording and pharmacological
      micromanipulations in awake monkeys to demonstrate that both competitive and
      noncompetitive NMDA antagonists block the generation of MMN without affecting
      prior obligatory activity in primary auditory cortex. These findings suggest
      that, on a neurophysiological level, MMN represents selective current flow
      through open, unblocked NMDA channels. Furthermore, they suggest a crucial role
      of cortical NMDA receptors in the assessment of stimulus
      familiarity/unfamiliarity, which is a key process underlying working memory
      performance.

PMID- 8876246
TI  - Identification of metabolic pathways of brain angiotensin II and III using
      specific aminopeptidase inhibitors: predominant role of angiotensin III in the
      control of vasopressin release.
AB  - Angiotensin (Ang) II and Ang III are two peptide effectors of the brain renin
      angiotensin system that participate in the control of blood pressure and increase
      water consumption and vasopressin release. In an attempt to delineate the
      respective roles of these peptides in the regulation of vasopressin secretion,
      their metabolic pathways and their effects on vasopressin release were identified
      in vivo. For this purpose, we used recently developed selective inhibitors of
      aminopeptidase A (APA) and aminopeptidase N (APN), two enzymes that are believed
      to be responsible for the N-terminal cleavage of Ang II and Ang III,
      respectively. Mice received [3H]Ang II intracerebroventricularly (i.c.v.) in the
      presence or absence of the APN inhibitor, EC33 (3-amino-4-thio-butyl sulfonate)
      of the APN inhibitor, EC27 (2-amino-pentan-1,5-dithiol). [3H]Ang II and [3H]Ang
      III levels were evaluated from hypothalamus homogenates by HPLC. EC33 increased
      the half-life of [3H]Ang II 2.6-fold and completely blocked the formation of
      [3H]Ang III, whereas EC27 increased the half-life of [3H]Ang III 2.3-fold. In
      addition, the effects of EC33 and EC27 on Ang-induced vasopressin release were
      studied in mice. Ang II was injected i.c.v. in the presence or absence of EC33,
      and plasma vasopressin levels were estimated by RIA. While vasopressin levels
      were increased 2-fold by Ang II (5 ng), EC33 inhibited Ang II-induced vasopressin
      release in a dose-dependent manner. In contrast, EC27 injected alone increased in
      a dose-dependent manner vasopressin levels. The EC27-induced vasopressin release
      was completely blocked by the coadministration of the Ang receptor antagonist
      (Sar1-Ala8) Ang II. These results demonstrate for the first time that (i) APA and
      APN are involved in vivo in the metabolism of brain Ang II and Ang III,
      respectively, and that (ii) the action of Ang II on vasopressin release depends
      upon the prior conversion of Ang II to Ang III. This shows that Ang III behaves
      as one of the main effector peptides of the brain renin-angiotensin system in the
      control of vasopressin release.

PMID- 8876247
TI  - Adenovirus-mediated gene delivery into neuronal precursors of the adult mouse
      brain.
AB  - Precursor cells found in the subventricular zone (SVZ) of the adult brain can
      undergo cell division and migrate long distances before differentiating into
      mature neurons. We have investigated the possibility of introducing genes stably
      into this population of cells. Replication-defective adenoviruses were injected
      into the SVZ of the lateral ventricle of adult mice. The adenoviruses carried a
      cDNA for the LacZ reporter or the human p75 neurotrophin receptor, for which
      species-specific antibodies are available. Injection of the viruses into the SVZ
      led to efficient labeling of neuronal precursors. Two months after viral
      injection, infected cells were detected in the olfactory bulb, a significant
      distance from the site of injection. Labeled periglomerular and granular neurons
      with extensive dendritic arborization were found in the olfactory bulb. These
      results demonstrate that foreign genes can be efficiently introduced into
      neuronal precursor cells. Furthermore, adenovirus-directed infection can lead to
      long-term stable gene expression in progenitor cells found in the adult central
      nervous system.

PMID- 8876248
TI  - The effects of stress on social preferences are sexually dimorphic in prairie
      voles.
AB  - Prairie voles (Microtus ochrogaster) are monogamous rodents that form pair bonds
      characterized by a preference for a familiar social partner. In male prairie
      voles, exposure to either the stress of swimming or exogenous injections of
      corticosterone facilitate the development of a social preference for a female
      with which the male was paired after injection or swimming. Conversely,
      adrenalectomy inhibits partner preference formation in males and the behavioral
      effects of adrenalectomy are reversed by corticosterone replacement. In female
      prairie voles, swim stress interferes with the development of social preferences
      and corticosterone treatments inhibit the formation of partner preferences, while
      adrenalectomized females form preferences more quickly than adrenally intact
      controls. Because sex differences in both behavior and physiology are typically
      reduced in monogamous species, we initially predicted that male and female
      prairie voles would exhibit similar behavioral responses to corticosterone.
      However, our findings suggest an unanticipated sexual dimorphism in the
      physiological processes modulating social preferences. This dimorphic involvement
      of stress hormones in pair bonding provides a proximate mechanism for regulating
      social organization, while permitting males and females to adapt their
      reproductive strategies in response to environmental challenges.

PMID- 8876249
TI  - Modeling back propagating action potential in weakly excitable dendrites of
      neocortical pyramidal cells.
AB  - Simultaneous recordings from the soma and apical dendrite of layer V neocortical
      pyramidal cells of young rats show that, for any location of current input, an
      evoked action potential (AP) always starts at the axon and then propagates
      actively, but decrementally, backward into the dendrites. This back-propagating
      AP is supported by a low density (-gNa = approximately 4 mS/cm2) of rapidly
      inactivating voltage-dependent Na+ channels in the soma and the apical dendrite.
      Investigation of detailed, biophysically constrained, models of reconstructed
      pyramidal cells shows the following. (i) The initiation of the AP first in the
      axon cannot be explained solely by morphological considerations; the axon must be
      more excitable than the soma and dendrites. (ii) The minimal Na+ channel density
      in the axon that fully accounts for the experimental results is about 20-times
      that of the soma. If -gNa in the axon hillock and initial segment is the same as
      in the soma [as recently suggested by Colbert and Johnston [Colbert, C. M. &
      Johnston, D. (1995) Soc. Neurosci. Abstr. 21, 684.2]], then -gNa in the more
      distal axonal regions is required to be about 40-times that of the soma. (iii) A
      backward propagating AP in weakly excitable dendrites can be modulated in a
      graded manner by background synaptic activity. The functional role of weakly
      excitable dendrites and a more excitable axon for forward synaptic integration
      and for backward, global, communication between the axon and the dendrites is
      discussed.

PMID- 8876250
TI  - An inhibitor of the microsomal triglyceride transfer protein inhibits apoB
      secretion from HepG2 cells.
AB  - The microsomal triglyceride (TG) transfer protein (MTP) is a heterodimeric lipid
      transfer protein that catalyzes the transport of triglyceride, cholesteryl ester,
      and phosphatidylcholine between membranes. Previous studies showing that the
      proximal cause of abetalipoproteinemia is an absence of MTP indicate that MTP
      function is required for the assembly of the apolipoprotein B (apoB) containing
      plasma lipoproteins, i.e., very low density lipoproteins and chylomicrons.
      However, the precise role of MTP in lipoprotein assembly is not known. In this
      study, the role of MTP in lipoprotein assembly is investigated using an inhibitor
      of MTP-mediated lipid transport, 2-[1-(3, 3-diphenylpropyl)-4-piperidinyl]-2,3
      dihydro-1H-isoindol-1-o ne (BMS-200150). The similarity of the IC50 for
      inhibition of bovine MTP-mediated TG transfer (0.6 microM) to the Kd for binding
      of BMS-200150 to bovine MTP (1.3 microM) strongly supports that the inhibition of
      TG transfer is the result of a direct effect of the compound on MTP. BMS-200150
      also inhibits the transfer of phosphatidylcholine, however to a lesser extent
      (30% at a concentration that almost completely inhibits TG and cholesteryl ester
      transfer). When BMS-200150 is added to cultured HepG2 cells, a human liver
      derived cell line that secretes apoB containing lipoproteins, it inhibits apoB
      secretion in a concentration dependent manner. These results support the
      hypothesis that transport of lipid, and in particular, the transport of neutral
      lipid by MTP, plays a critical role in the assembly of apoB containing
      lipoproteins.

PMID- 8876251
TI  - Correction of hypertension by normalization of endothelial levels of fibroblast
      growth factor and nitric oxide synthase in spontaneously hypertensive rats.
AB  - Acidic and basic fibroblast growth factors (FGFs) share a wide range of diverse
      biological activities. To date, low levels of FGF have not been correlated with a
      pathophysiologic state. We report that blood vessels of spontaneously
      hypertensive rats are shown to be associated with a marked decrement in
      endothelial basic FGF content. This decrement correlates both with hypertension
      and with a decrease in the endothelial content of nitric oxide synthase.
      Restoration of FGF to physiological levels in the vascular wall, either by
      systemic administration or by in vivo gene transfer, significantly augmented the
      number of endothelial cells with positive immunostaining for nitric oxide
      synthase, corrected hypertension, and ameliorated endothelial-dependent responses
      to vasoconstrictors. These results suggest an important role for FGFs in blood
      pressure homeostasis and open new avenues for the understanding of the etiology
      and treatment of hypertension.

PMID- 8876252
TI  - Estradiol stimulates tyrosine phosphorylation of the insulin-like growth factor-1
      receptor and insulin receptor substrate-1 in the uterus.
AB  - The signaling pathways associated with estrogen-induced proliferation of
      epithelial cells in the reproductive tract have not been defined. To identify
      receptor tyrosine kinases that are activated in vivo by 17 beta-estradiol (E2),
      uteri from ovariectomized mice were examined for enhanced tyrosine
      phosphorylation of various receptors and a receptor substrate following treatment
      with this hormone. Within 4 hr after hormone exposure, extracts showed increased
      phosphotyrosine (P-Tyr) immunoreactivity at several bands, including 170- and 180
      kDa; these bands were still apparent at 24 hr after E2. Analysis of
      immunoprecipitates from uterine extracts revealed that E2 enhanced tyrosine
      phosphorylation of the insulin-like growth factor-1 receptor (IGF-1R) and insulin
      receptor substrate-1 (IRS-1) by 6 hr. Comparison of supernatants from IRS-1 and
      control rabbit IgG immunoprecipitates indicated that the 170-kDa P-Tyr band in
      extracts was equivalent to IRS-1. The receptors for epidermal growth factor,
      platelet-derived growth factor, and basic fibroblast growth factor did not
      exhibit an E2-induced increase in P-Tyr content. The nonestrogenic steroid
      hormones examined did not stimulate the P-Tyr content of IGF-1R or IRS-1.
      Immunolocalization of P-Tyr and IRS-1 revealed strong reactivity in the
      epithelial layer of the uterus from E2-treated mice, suggesting that the majority
      of P-Tyr bands observed in immunoblots originate in the epithelium. Since
      hormonal activation of IRS-1 is epithelial, estrogen-specific, and initiated
      before maximal DNA synthesis occurs following treatment with hormone, this
      protein, as part of the IGF-1R pathway, may be important in mediating estrogen
      stimulated proliferation in the uterus.

PMID- 8876253
TI  - Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach.
AB  - The structural relationships between interstitial cells of Cajal (ICC), varicose
      nerve fibers, and smooth muscle cells in the gastrointestinal tract have led to
      the suggestion that ICC may be involved in or mediate enteric neurotransmission.
      We characterized the distribution of ICC in the murine stomach and found two
      distinct classes on the basis of morphology and immunoreactivity to antibodies
      against c-Kit receptors. ICC with multiple processes formed a network in the
      myenteric plexus region from corpus to pylorus. Spindle-shaped ICC were found
      within the circular and longitudinal muscle layers (IC-IM) throughout the
      stomach. The density of these cells was greatest in the proximal stomach. IC-IM
      ran along nerve fibers and were closely associated with nerve terminals and
      adjacent smooth muscle cells. IC-IM failed to develop in mice with mutations in c
      kit. Therefore, we used W/W(V) mutants to test whether IC-IM mediate neural
      inputs in muscles of the gastric fundus. The distribution of inhibitory nerves in
      the stomachs of c-kit mutants was normal, but NO-dependent inhibitory neuro
      regulation was greatly reduced. Smooth muscle tissues of W/W(V) mutants relaxed
      in response to exogenous sodium nitroprusside, but the membrane potential effects
      of sodium nitroprusside were attenuated. These data suggest that IC-IM play a
      critical serial role in NO-dependent neurotransmission: the cellular mechanism(s)
      responsible for transducing NO into electrical responses may be expressed in IC
      IM. Loss of these cells causes loss of electrical responsiveness and greatly
      reduces responses to nitrergic nerve stimulation.

PMID- 8876254
TI  - Depletion of intracellular polyamines relieves inward rectification of potassium
      channels.
AB  - Two different approaches were used to examine the in vivo role of polyamines in
      causing inward rectification of potassium channels. In two-microelectrode voltage
      clamp experiments, 24-hr incubation of Xenopus oocytes injected with 50 nl of
      difluoromethylornithine (5 mM) and methylglyoxal bis(guanylhydrazone) (1 mM)
      caused an approximate doubling of expressed Kir2.1 currents and relieved
      rectification by causing an approximately +10-mV shift of the voltage at which
      currents are half-maximally inhibited. Second, a putrescine auxotrophic,
      ornithine decarboxylase-deficient Chinese hamster ovary (O-CHO) cell line was
      stably transfected with the cDNA encoding Kir2.3. Withdrawal of putrescine from
      the medium led to rapid (1-day) loss of the instantaneous phase of Kir2.3 channel
      activation, consistent with a decline of intracellular putrescine levels. Four
      days after putrescine withdrawal, macroscopic conductance, assessed using an
      86Rb+ flux assay, was approximately doubled, and this corresponded to a +30-mV
      shift of V1/2 of rectification. With increasing time after putrescine withdrawal,
      there was an increase in the slowest phase of current activation, corresponding
      to an increase in the spermine-to-spermidine ratio over time. These results
      provide direct evidence for a role of each polyamine in induction of
      rectification, and they further demonstrate that in vivo modulation of
      rectification is possible by manipulation of polyamine levels using genetic and
      pharmacological approaches.

PMID- 8876255
TI  - Autocrine signaling through ATP release represents a novel mechanism for cell
      volume regulation.
AB  - Recovery of cell volume in response to osmotic stress is mediated in part by
      increases in the Cl- permeability of the plasma membrane. These studies evaluate
      the hypothesis that ATP release and autocrine stimulation of purinergic (P2)
      receptors couple increases in cell volume to opening of Cl- channels. In HTC rat
      hepatoma cells, swelling induced by hypotonic exposure increased membrane Cl-
      current density to 44.8 +/- 7.1 pA/pF at -80 mV. Both the rate of volume recovery
      and the increase in Cl- permeability were inhibited in the presence of the ATP
      hydrolase apyrase (3 units/ml) or by exposure to the P2 receptor blockers suramin
      and Reactive Blue 2 (10-100 microM). Cell swelling also stimulated release of
      ATP. Hypotonic exposure increased the concentration of ATP in the effluent of
      perfused cells by 170 +/- 36 nM in the presence of a nucleotidase inhibitor (P <
      0.01). In whole-cell recordings with ATP as the charge carrier, cell swelling
      increased membrane current density approximately 30-fold to 16.5 +/- 10.4 pA/pF.
      These findings indicate that increases in cell volume lead to efflux of ATP
      through opening of a conductive pathway consistent with a channel, and that
      extracellular ATP is required for recovery from swelling. ATP may function as an
      autocrine factor that couples increases in cell volume to opening of Cl- channels
      through stimulation of P2 receptors.

PMID- 8876257
TI  - Discovery of an algal mitochondrial carbonic anhydrase: molecular cloning and
      characterization of a low-CO2-induced polypeptide in Chlamydomonas reinhardtii.
AB  - In green unicellular algae, several polypeptides are induced upon exposure to
      limiting CO2. We report here on the localization and characterization of one of
      these, a 22-kDa polypeptide in Chlamydomonas reinhardtii. This nuclear-encoded
      polypeptide is induced in the mitochondria by a lowering of the partial pressure
      of CO2 in the growth medium from 5% to air CO2 levels. Sequencing of two
      different cDNA clones coding for the polypeptide identified it as a 20.7-kDa beta
      type carbonic anhydrase (CA; carbonate dehydratase, carbonate hydro-lyase, EC
      4.2.1.1). The two clones differ in their nucleotide sequences but code for
      identical proteins, showing that this CA is encoded by at least two genes.
      Northern blot hybridization reveals that mRNA transcripts are only present in
      cells transferred to air CO2 levels. A comparison of the deduced amino acid
      sequence with those of other beta-CAs shows the largest degree of similarity with
      CA from the cyanobacterium Synechocystis (50% identity and 66% similarity). To
      our knowledge, this is the first identification and characterization of a
      mitochondrial CA from a photosynthetic organism.

PMID- 8876258
TI  - Paternal and maternal DNA lineages reveal a bottleneck in the founding of the
      Finnish population.
AB  - An analysis of Y-chromosomal haplotypes in several European populations reveals
      an almost monomorphic pattern in the Finns, whereas Y-chromosomal diversity is
      significantly higher in other populations. Furthermore, analyses of nucleotide
      positions in the mitochondrial control region that evolve slowly show a decrease
      in genetic diversity in Finns. Thus, relatively few men and women have
      contributed the genetic lineages that today survive in the Finnish population.
      This is likely to have caused the so-called "Finnish disease heritage"-i.e., the
      occurrence of several genetic diseases in the Finnish population that are rare
      elsewhere. A preliminary analysis of the mitochondrial mutations that have
      accumulated subsequent to the bottleneck suggests that it occurred about 4000
      years ago, presumably when populations using agriculture and animal husbandry
      arrived in Finland.

PMID- 8876259
TI  - Activation of memory circuits during cue-elicited cocaine craving.
AB  - Evidence accumulated over more than 45 years has indicated that environmental
      stimuli can induce craving for drugs of abuse in individuals who have addictive
      disorders. However, the brain mechanisms that subserve such craving have not been
      elucidated. Here a positron emission tomographic study shows increased glucose
      metabolism in cortical and limbic regions implicated in several forms of memory
      when human volunteers who abuse cocaine are exposed to drug-related stimuli.
      Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial
      temporal lobe (amygdala), and cerebellum with self-reports of craving suggest
      that a distributed neural network, which integrates emotional and cognitive
      aspects of memory, links environmental cues with cocaine craving.

PMID- 8876260
TI  - Faithful representation of similarities among three-dimensional shapes in human
      vision.
AB  - Efficient and reliable classification of visual stimuli requires that their
      representations reside a low-dimensional and, therefore, computationally
      manageable feature space. We investigated the ability of the human visual system
      to derive such representations from the sensory input-a highly nontrivial task,
      given the million or so dimensions of the visual signal at its entry point to the
      cortex. In a series of experiments, subjects were presented with sets of
      parametrically defined shapes; the points in the common high-dimensional
      parameter space corresponding to the individual shapes formed regular planar (two
      dimensional) patterns such as a triangle, a square, etc. We then used
      multidimensional scaling to arrange the shapes in planar configurations, dictated
      by their experimentally determined perceived similarities. The resulting
      configurations closely resembled the original arrangements of the stimuli in the
      parameter space. This achievement of the human visual system was replicated by a
      computational model derived from a theory of object representation in the brain,
      according to which similarities between objects, and not the geometry of each
      object, need to be faithfully represented.

PMID- 8876261
TI  - Sequence verification of human creatine kinase (43 kDa) isozymes by high
      resolution tandem mass spectrometry.

PMID- 8876262
TI  - Reproductive parameters of older compared to younger men of infertile couples.
AB  - In order to evaluate possible age-dependent influences on male infertility, semen
      parameters, sex hormone levels and pregnancy rates were compared retrospectively
      in three groups of men attending our fertility clinic: group A: 39 patients > 50
      years. Group B (39 patients < 30 years) was established as the 'standard
      infertile patient' seen in our Institute. These patients were matched with
      patients of group A according to the year of their first visit to the clinic.
      Group C: 39 young patients (< 30 years) who were selected on the basis of their
      wives' advanced age. The frequency of sexual intercourse in group A was
      significantly lower compared to group C. The period of sexual abstinence was
      longer in group A than in group B. Ejaculate volume and sperm motility in group A
      were lower compared to groups B and C. The differences in other semen parameters
      were only minor. The differences in serum levels of testosterone and FSH were
      significant between group A and groups B and C. Pregnancies were reported in 6 of
      26 couples from group A (duration of infertility: mean 79 months, range 16-187),
      in 17 of 28 couples from group B (duration of infertility; mean 54 months, range
      16-104) and in nine of 30 couples from group C (duration of infertility; mean 66
      months, range 25-125). Since the infertility pattern of the older patients
      desiring offspring was not significantly different from that of younger patients,
      it is concluded that the age of the female partner, rather than the age of the
      husband, is most important in determining the fertility chances of couples
      presenting with infertility.

PMID- 8876263
TI  - The effect of bradykinin and the bradykinin antagonist Hoe 140 on kinematic
      parameters of human spermatozoa.
AB  - Bradykinin (BK) has been suggested to be an active substance in the disputed
      therapeutic use of kallikrein to improve semen quality. The effects of exogenous
      BK and its antagonist Hoe 140, which acts on one of the bradykinin receptors
      (BK2), were examined in two groups of patients attending the fertility clinic:
      those with asthenozoospermia (group I) and normozoospermia (group II). Bradykinin
      (10nM-1 microM) added to washed human spermatozoa had no effect on most kinematic
      parameters and caused only a marginal increase (7%) in curvilinear velocity at 50
      nM in group I patients; however, this increase was not suppressed by concomitant
      addition of the BK antagonist. The bradykinin antagonist itself had no effect on
      the percentage motility or kinematic motility parameters of washed human
      spermatozoa in either group of patients. The motility of spermatozoa in semen was
      also unaffected by the presence of the bradykinin antagonist. It is concluded
      that bradykinin does not act exogenously on washed spermatozoa nor endogenously
      on spermatozoa in semen to stimulate motility via BK2 receptors, regardless of
      the initial quality of the sperm motility.

PMID- 8876264
TI  - A placebo-controlled flow cytometric study of the effect of low-dose prednisolone
      treatment on sperm-bound antibody levels.
AB  - In this placebo-controlled study the effect of short term, low-dose prednisolone
      treatment on sperm-bound antibody levels was investigated using an objective flow
      cytometric (FCM) measurement. Twenty infertile men, positive for antisperm
      antibodies by the mixed antiglobulin reaction (MAR) test, were treated with
      either 20 mg/day prednisolone (n = 10) or placebo (n = 10) for 3 weeks. The two
      groups were similar with respect to sperm count, motility and antibody levels.
      The proportion of spermatozoa positive for IgG and IgA antibodies and the
      antibody load, expressed as the number of IgG and IgA antibody molecules bound
      per spermatozoa were measured by FCM. The study showed that, overall, the
      antibody levels measured before and after treatment with low-dose prednisolone or
      with placebo were not statistically different. However, in the prednisolone group
      a marked decrease in the proportion of spermatozoa positive for IgG and IgA
      antibodies was observed in two of the patients. An examination of the FCM data of
      these two patients revealed that, in their ejaculates, only the spermatozoa with
      low to moderate amounts of sperm-bound antibodies had responded to prednisolone
      treatment, while spermatozoa with high levels of sperm antibodies had remained
      resistant to prednisolone. These results point to the existence of an as-yet
      undefined subset of prednisolone-responsive, antibody--positive spermatozoa.

PMID- 8876265
TI  - Glutathione S-transferase-M1 'null' genotype and alcohol-induced disorders of
      human spermatogenesis.
AB  - The association between alcohol-induced disorders of human spermatogenesis and
      glutathione S-transferase-M1 genotype was investigated in an autopsy study
      comprising 271 subjects, including interviews with relatives or close
      acquaintances on the alcohol consumption of the deceased. Of the 50 moderate
      drinking men (reported mean daily alcohol consumption < 40 g), 21 (42.0%) had
      normal spermatogenesis, whereas 24 men (48.0%) had partial, and five (10.0%)
      complete arrest of spermatogenesis. Of the 21 men with normal spermatogenesis,
      nine (42.9%) had GST M1 'null' genotype, while this genotype was found in 13
      (44.8%) of the 29 men with partial or complete spermatogenic arrest. Of 212 heavy
      drinking men (reported mean daily alcohol consumption > 80 g), only 45 (21.2%)
      had normal spermatogenesis, whereas 77 (36.3%) had partial spermatogenic arrest.
      Complete arrest of spermatogenesis was found in 81 men (38.2%) and nine men had
      Sertoli-cell-only syndrome (4.2%). Of the 45 heavy drinkers with normal
      spermatogenesis, 27 (60%) men had GST M1 'null' genotype (OR 2.7 with 95%
      confidence intervals: 1.0-4.0, when compared to those with disorders of
      spermatogenesis). The frequency of GST M1 'null' genotype in heavy drinkers with
      normal spermatogenesis also differed from that of corresponding moderate
      drinkers, whereas the frequency of GST M1 'null' genotype in heavy drinkers with
      disorders of spermatogenesis was similar to moderate drinkers with or without
      disorders of spermatogenesis. The finding that > 20% of men in the heavy-drinking
      group had normal spermatogenesis suggests individual variations in sensitivity to
      alcohol-induced disorders of this process. Heavy drinkers with GST M1 'null'
      genotype were slightly less prone to develop disorders of spermatogenesis. Thus,
      the GST M1 locus may be associated with susceptibility to develop alcohol-induced
      disorders of spermatogenesis.

PMID- 8876266
TI  - Testicular gamma-aminobutyric acid and circulating androgens in Syrian and
      Djungarian hamsters during sexual development.
AB  - Several factors, besides luteinizing hormone (LH), participate in the modulation
      of testicular function. A number of neurotransmitters are reported to be involved
      in this process, including a stimulatory action of gamma-aminobutyric acid (GABA)
      on steroidogenesis in the rat testis. The purpose of this study was to
      investigate the testicular pattern of GABA and glutamic acid, one of its main
      precursors, during sexual maturation in two seasonally breeding species: Syrian
      (golden) and Djungarian hamsters. Plasma androgen levels were also measured. The
      animals were maintained under long-day photoperiod (16:8, L:D) and were killed at
      23, 30, 36, 46, 60, and 90 days of age. A different pattern of developmental
      changes in body and testicular weight was observed in these two species. GABA was
      present in the testes at all ages studied. GABA concentration and content showed
      a sharp elevation in the prepubertal period in golden as well as Djungarian
      hamsters. However, glutamic acid concentrations remained nearly constant during
      development in both species. Glutamic acid content increased gradually with age
      in the golden hamster, while a marked peak at 36 days of age was detected in the
      Djungarian hamster. Plasma testosterone and dihydrotestosterone levels were
      maximal at pubertal age in both species. The plasma levels of 5 alpha-androstane
      3 alpha, 17 beta-diol increased significantly at 30 days of age in the golden
      hamster while in Djungarian hamsters this steroid remained unchanged. These
      results suggest that glutamic acid may serve as a precursor for GABA biosynthesis
      in the testis. In addition, changes in testicular GABA and plasma androgen levels
      might reflect a modulatory effect of this neurotransmitter in the acquisition of
      steroidogenic capability during development.

PMID- 8876267
TI  - Influence of photoinhibition on GABA and glutamic acid levels, and on glutamate
      decarboxylase activity in the testis and epididymis of the golden hamster.
AB  - Gamma-aminobutyric acid (GABA) is found in the gonads and accessory reproductive
      organs, and a direct effect on steroidogenesis and sperm viability and motility
      has been described. The golden (Syrian) hamster is a seasonal breeder, and a
      pattern of regression-recrudescence in their reproductive organs is observed when
      adult animals are exposed to less than 12.5 h daylight for an extended period of
      time. The purpose of this study was to investigate: (1) the presence of GABA in
      the testis and epididymis of golden hamsters undergoing regression and
      spontaneous recrudescence; (2) glutamic acid levels and glutamate decarboxylase
      (GAD) activity in both tissues, and (3) testicular and epididymal testosterone,
      dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol concentrations.
      Adult golden hamsters were exposed to long (LP 14L:10D) or short (SP 6L:18D)
      photoperiods for 9, 12, 14, 16, 18 or 22 weeks. When animals were exposed to SP
      for 14-16 weeks, the testis and epididymis reached maximal involution. Testicular
      and epididymal androgen levels showed a marked decrease (p < 0.05) during the
      regression period, and after 18-22 weeks, values began to recover. Between 12 and
      18 weeks in SP, the testicular and epididymal content of GABA and glutamic acid
      was reduced significantly. The concentration of GABA in both tissues showed a
      sharp rise (p < 0.05), while the concentration of glutamic acid diminished during
      the period of maximal involution (p < 0.05). In the testis, GAD activity was
      increased (p < 0.001) after 14 weeks in SP, with no change in the epididymis. In
      conclusion, glutamic acid via GAD activity could be the main source of GABA in
      the testis, but not in the epididymis. Furthermore, the presence of GABA in
      testicular cells and its subsequent photoperiodic variations might act as an
      important autocrine and/or paracrine modulatory signal in gonadal processes.

PMID- 8876268
TI  - Infection with Trypanosoma brucei potentiates the antifertility effect of
      gossypol, especially in the protein-malnourished male rat.
AB  - Reproductive parameters were investigated in gossypol-treated male rats that had
      been infected experimentally with Trypanosoma brucei and then place on one of two
      diets of differing (low and normal) protein content. The endpoints assessed were
      reproductive organ weights, semen epididymal sperm counts, serum testosterone and
      histological, stereological and histomorphometric evaluation of the testis and
      accessory reproductive organs. Most of the parameters studied were lowest in the
      protein-malnourished, gossypol-treated, trypanosome-infected animals, when
      compared to those obtained from the corresponding animals that were only gossypol
      treated or trypanosome-infected. Mean testicular size and the diameter and the
      total length of seminiferous tubules were especially reduced, indicating that the
      overall volume of the seminiferous epithelium in these animals was smaller. These
      findings suggest that reproductive capacity could be impaired in protein
      malnourished, trypanosome-infected animals fed on gossypol-containing products,
      even when there are no obvious clinical signs of disease. This could translate
      into increased production costs in a farm enterprise. Screening for
      haemoparasitism would also seem to be worthwhile prior to evaluation and/or use
      of gossypol (or perhaps other potential contraceptives) in human subjects,
      especially in communities that are confronted with severe food shortages.

PMID- 8876269
TI  - Sertoli cell barrier dysfunction and spermatogenetic cycle breakdown in the human
      testis: a lanthanum tracer investigation.
AB  - The introduction of nitrate of lanthanum in fixative solutions for testicular
      biopsies improves ultrastructural observations of the blood-testis barrier. In
      complete (normal) spermatogenesis, junctional specializations impede the
      diffusion of lanthanum into the adluminal compartment. They clearly exhibit a
      three-storied disposition in orthogonal sections. In maturation arrest, lanthanum
      passes easily through the junctional specializations surrounding the germ cells
      and up to the lumen. In irregular hypospermatogenesis, the Sertoli cell barrier
      is permeable, but diffusion of the tracer is less significant and variable.
      Unexpectedly, in germ cell aplasia, the barrier remains efficient

PMID- 8876270
TI  - Occurrence of desmoid tumours in familial adenomatous polyposis and results of
      treatment.
AB  - Desmoids are of major concern in patients with familial adenomatous polyposis
      (FAP) besides the cancer risk. We estimated the risk for desmoid tumours and the
      results of their treatment in the Finnish Polyposis Registry. The analysis
      included 202 FAP patients, of whom 169 had undergone colectomy. Desmoids were
      observed in 29 cases: 15 in the mesentery, 10 in the abdominal wall and 4 in
      other sites. There were 12 male and 17 female patients with a mean age of 28.2
      years (range 7 months to 59 years). The cumulative life-time risk was 21%; 1.5,
      3.0, 8.9, 16 and 18% at ages of 10, 20, 30, 40 and 50 years, respectively. The
      risk of postcolectomy desmoids was 17% after ileorectal anastomosis and 12% after
      proctocolectomy. There were no deaths due to desmoids. One abdominal scar desmoid
      disappeared spontaneously and all the other abdominal wall desmoids could be
      excised without complications, but recurrence occurred in five (45%) cases.
      Excision was possible in only nine mesenteric desmoids (56%); in these cases
      recurrence was less common (two cases, 22%) but two others had life-threatening
      complications (bleeding, short bowel). We conclude that the desmoid problem
      concerns more than 20% of all FAP patients in long-term. Despite high recurrence
      rates and surgical hazards surgery remains a useful option for most desmoid
      tumours in FAP patients considering that other treatments are often ineffective
      or hazardous as well.

PMID- 8876271
TI  - Clinical, manometric and sonographic assessment of the anal sphincters. A
      comparative prospective study.
AB  - One hundred patients with various anorectal disorders but intact anal sphincters
      were evaluated prospectively by three independent observers to determine the
      specificity, sensibility and accuracy of digital exploration and anal ultrasound
      compared to anal manometry, in assessing internal and sphincter hypertonicity
      (IH) and the relaxation of sphincters on straining (SR). Accuracy of the digital
      examination in evaluating IH was 80 vs 74%, while the SR was detected by the
      three observers in 82, 71 and 65% of cases. The thickness of internal sphincter
      increased with age (r = 0.37, P = 0.01), whereas the resting tone decreased with
      age (r = 0.27, P = 0.06). There was an inverse correlation between the
      sonographic thickness of the internal sphincter and the manometric resting tone
      (r = 0.29, P = 0.004). The internal sphincter thickness was 1.97 +/- 0.41 mm in
      constipated patients, 2.06 +/- 0.39 in the others (P = 0.03). In conclusion, IH
      and SR may be assessed by digital exploration with a good accuracy and the
      thickness of internal sphincter at ultrasound may change according to its
      functional state.

PMID- 8876272
TI  - Is digitation associated with proctographic abnormality?
AB  - Constipated patients referred for evacuation proctography were questioned as to
      the need for digital manoeuvres to assist evacuation, to determine the frequency
      of digitation, and to investigate whether any proctographic feature was
      associated with this symptom. Seventy one percent of patients interviewed
      admitted to digitation. Proctographic findings in 20 constipated patients who
      digitated per vagina and 20 who digitated per anum were compared to 20 who did
      not. There was no significant difference between groups with respect to pelvic
      floor descent, anal canal width or any anrectal angle measurement. Rectocoele
      depth and area were significantly greater in patients who digitated per vagina,
      compared to the other two groups. Evacuation time was prolonged and a
      proctographic diagnosis of anismus more frequent, in patients who digitated per
      anum. Anal digitation is associated with prolonged evacuation, suggesting a
      proctographic diagnosis of anismus and vaginal digitation to assist rectal
      evacuation is significantly associated with large anterior rectocoele.

PMID- 8876273
TI  - Clinico-physiological results after sphincter-saving resection for rectal
      carcinoma.
AB  - In this study, we evaluated the postoperative functional results after resection
      of rectal carcinoma. A questionnaire and anal manometry were used to evaluate the
      severity of the symptoms. The patients were divided into the three groups of
      anterior resection (AR, 38 patients), low anterior resection (LAR, 34 patients)
      and stapled colo-anal anastomosis (SCA, 20 patients). Manometric examination and
      questionnaire evaluation were performed 1, 3, 6, and 12 months after the
      operation. The SCA group showed by far the poorest outcome in terms of soiling
      and urgency at 12 months. Anal sensation was recovered by 12 months in each
      group. Incomplete evacuation was frequently observed in the SCA and LAR groups.
      Each anal manometric parameter recovered in the AR group, but the maximum
      tolerable volume of the neorectum did not recover in either the SCA or LAR group.
      The threshold volume of the SCA group was lower than those in the other two
      groups. The reservoir function of the neorectum, which is composed of the
      colorectal muscle layer and nervous components, plays a role in maintenance of
      bowel function.

PMID- 8876274
TI  - Suprapubic versus transurethral catheterisation of males undergoing pelvic
      colorectal surgery.
AB  - A prospective, randomised double-blind trial of suprapubic (SPC) versus
      transurethral (TUC) catheterisation was undertaken in fifty consecutive male
      patients of median age 66 (range 32-81) years undergoing pelvic colorectal
      surgery. Twenty-four patients were randomised to SPC. Catheter removal times were
      comparable between the two groups: SPC = mean 7.2 (3-14) days; TUC = man 7.5 (2
      13) days; P > 0.5. Acute urinary retention was recorded in 5 patients with SPC
      and 6 in the TUC group. Chronic retention with overflow was recorded in one TUC
      patient. Frequent voiding after catheter removal occurred in two SPC, and in
      eleven TUC patients (P < 0.05). Re-catheterization was required in two SPC, and
      seven TUC patients. One culture positive urinary tract infection occurred in the
      SPC, and three in the TUC groups. It is concluded that suprapubic catheterisation
      allows comparable controlled return of normal voiding with fewer bladder and
      urethral symptoms when compared with transurethral catheterisation.

PMID- 8876275
TI  - Intestinal haemorrhage after strictureplasty for Crohn's disease.
AB  - Between 1978 and 1995, a total of 52 patients have undergone 241 small intestinal
      strictureplasties at 76 operations in one surgical unit. The post-operative
      course was complicated by intestinal haemorrhage in 4 patients. In 3, the
      bleeding settled with conservative management. The 4th patient required
      laparotomy on two occasions to control bleeding from duodenal Crohn's disease and
      the proximal jejunal strictureplasty site, respectively. Strictureplasty is a
      relatively safe operation, but has a low incidence of potentially life
      threatening post-operative haemorrhage.

PMID- 8876276
TI  - Comparison of two techniques of transrectal ultrasonography for the assessment of
      local extent of polypoid tumours of the rectum.
AB  - The capability of transrectal ultrasonography (TRUS) to differentiate between
      benign and malignant rectal polyps was evaluated. Digital palpation and
      sigmoidoscopy were followed by TRUS with a 7.5-MHz linear-array transducer, in a
      blinded design. In the second part of the study the procedure was extended with
      an acoustic window system (AWS), preventing compression of the polyp.
      Pathological examination after surgical resection was used for definitive
      diagnosis in 110 polyps. Digital examination detected 10 of 22 carcinomas with
      adenomas, compared with 19 by TRUS (P < 0.01). However, TRUS falsely indicated 20
      of 49 adenomas to be carcinomas, compared with 4 out of 49 by digital examination
      (P < 0.001). TRUS combined with AWS detected 23 of 24 carcinomas, and gave a
      false positive result in only 3 of 26 benign polyps. The results suggest that the
      best way to discriminate between benign and malignant rectal polyps is to combine
      TRUS with AWS.

PMID- 8876277
TI  - Biofeedback for anismus in 15 sexually abused women.
AB  - This work aimed to see whether (1) biofeedback is useful and (2) whether it needs
      to be combined with psychotherapy in sexually abused patients with anismus.
      Fifteen women aged 41.2 +/- 4.1 years who had experienced sexual abuse in
      childhood (9 cases) or adulthood (6 cases) and complained of symptoms of
      irritable bowel disease were studied. Anismus was recorded during anorectal
      manometry in all cases. Patients were free to choose biofeedback and/or group
      psychotherapy and/or individual psychotherapy. When necessary, psychoactive drugs
      were prescribed after a psychiatric evaluation. Initially all the patients chose
      biofeedback and none accepted psychotherapy. Eight patients accepted
      psychotherapy after several weeks of biofeedback. Thirteen patients completed the
      study: 5 treated by biofeedback alone, 5 with biofeedback and group therapy, and
      3 with biofeedback and individual psychotherapy. Eight women recovered completely
      from their symptoms, only two of whom had had biofeedback without psychotherapy.
      CONCLUSION: Biofeedback alone was not always sufficient to cure abused patients,
      but was chose initially by all the patients. It could initially be a middle path
      between somatic treatment and psychotherapy, at a time when patients are not yet
      ready to undertake the latter.

PMID- 8876278
TI  - Anterior resection: do the patients perceive any clinical benefit?
AB  - PURPOSE: Functional results following anterior resection of the rectum have been
      sparsely reported. Results concerning stool frequency and continence vary widely.
      These variations may represent several areas of bias, but one of the main
      concerns is study design. Many studies are focused on physiological results and
      even when a control population is included in the study design, it is not used to
      compare the clinical functional outcome. the aims of this prospective study were:
      (1) to study serially before and 1 year after low anterior resection for
      carcinoma the changes in clinical function; and (2) to study if these changes
      could be attributable to the characteristics of the population, comparing the
      results with sex-matched and age-matched controls. MATERIAL AND METHODS: Sample
      size was previously established according the prevalence of continence disorders
      fund in two previous studies carried out in our country, 36% for anterior
      resection, and 6% among general population in our community. Thirty-eight
      consecutive patients (mean age 63.9 years, range 41-77 years) with a diagnosis of
      rectal carcinoma were invited to participate in the study. The lower margin of
      the tumor was located between 4 and 15 cm from the anal margin (median of level
      tumor 6.0 cm). A control group of 25 volunteers matched for sex and age with
      patients who were questioned 1 year after the anterior resection were also
      studied. Median level of anastomosis was 6.2 +/- 2.7 cm (range 2-11) above the
      anal margin. In six patients with an anastomosis less than 4 cm from the anal
      margin, a loop ileostomy was constructed and closed 3 months later. Patients were
      interviewed by a research assistant before and 1 year after operation or 1 year
      after closure of the temporary defunctioning loop ileostomy. Patients were
      questioned about bowel frequency over 24 h, urgency, tenesmus, erratic defecatory
      patterns, discrimination of bowel content and continence. RESULTS: Clinical
      function of patients before and after operation. Compared with pre-operative,
      bowel frequency of 3.9/day (range 0.3-14) did not differ significantly 1 year
      after operation at 2.3/day (range 0.5-6). Frequency of erratic defecatory
      patterns (44%), urgency (40%) and obstructed defecation (20%) did not differ
      between the preoperative and postoperative period. Forty-eight percent of
      patients suffered tenesmus and 20% were unable to discriminate between flatus and
      feces before operation, whereas these troublesome symptoms were present in 24%
      and 16%, respectively, after the operation. Before the operation 32% of patients
      reported fecal leaks while in the postoperative period 52% patients complained of
      this alteration. Clinical function of patients compared with controls. Patients
      had a mean stool frequency per day of 2.3 (range 0.5-6) and controls 1.3 (range
      0.3-5). Forty-four percent of patients had erratic defecatory patterns, 24%
      suffered tenesmus and 40% urgency, whereas these troublesome symptoms were
      present in 12% in the control population. Moreover, obstructed defecation was
      present in 20% and 4%, respectively. All controls and 84% of patients maintained
      discrimination of flatus, liquid and solid feces. Fifty-two percent of patients
      and 8% of controls suffered from altered continence. CONCLUSIONS: One year after
      low anterior resection patients had poor bowel function when compared with a
      control population of the same age and sex. A distinct anterior resection
      syndrome exists consisting of increased bowel frequency, erratic defecatory
      patterns, urgency, tenesmus, obstructed defecation, and minor fecal leakage.
      Furthermore, these disturbances in defecatory function did not differ
      significantly from symptoms produced by the rectal carcinoma, and patients
      experienced no major benefit from surgery from a functional point of view.

PMID- 8876279
TI  - Digital ischemia and occult malignancy.
AB  - Since the early transcript by Raynaud and Trousseau, there has been wide
      acceptance of the association of occult malignancy and peripheral vascular
      disease. Recently, there have been a few case reports of acute onset monophasic
      digital ischemia heralding an occult malignancy. It appears that the site and
      tumor types seem unimportant in the development of ischemia; tumor resection
      however, usually results in rapid improvement of the affected digit. The
      mechanism remains to be established.

PMID- 8876280
TI  - An unusual presentation of intestinal lymphangiectasia.
AB  - Intestinal lymphangiectasia is a rare disorder, usually presenting with protein
      losing enteropathy leading to oedema and ascites. We describe a case that
      presented as an acute surgical emergency with pain and a mass in the right iliac
      fossa, which was successfully treated by resection of the involved segment of
      ileum.

PMID- 8876281
TI  - "Fistula in ano: a surgical audit".

PMID- 8876282
TI  - Abdominal resection rectopexy versus Delorme's procedure for rectal prolapse:
      comparison of clinical and physiological outcomes.

PMID- 8876283
TI  - Target of skin tumorigenesis: cyclin D1-cdk4.

PMID- 8876284
TI  - Chronic dermatophytosis syndrome due to Trichophyton rubrum.

PMID- 8876285
TI  - Epidemiology of Behcet's syndrome in Turkey.

PMID- 8876286
TI  - "I will use my power to help the sick to the best of my ability and judgement"
      (Hippocratic oath)

PMID- 8876287
TI  - Behcet's disease: clinical study of Jordanian patients.
AB  - BACKGROUND: Behcet's disease is a chronic, recurrent, inflammatory disorder
      characterized by the triad of oral and genital ulcers and ocular lesions. The
      etiology is unknown. This is the first report giving details of the clinical
      manifestations of Behcet's disease in Jordanian patients. METHODS: Twenty
      patients with Behcet's disease were studied to determine the clinical pattern in
      the North of Jordan. The patients were seen in Princess Basma Teaching Hospital
      in North Jordan. They presented to various clinics and underwent full clinical
      examination. Data for each patient on all features of Behcet's disease were
      recorded on a standard form. A comparison was made between Behcet's disease in
      Jordan and other countries in the region. RESULTS: Of the 20 patients, 14 were
      men and six women, giving a ratio of 2.3:1. Their ages ranged from 14 to 58
      years. All had mouth ulcers, 65% genital ulcers, 65% ocular involvement, 55%
      joint involvement, 35% skin lesions, 20% vascular lesions, and 5%
      gastrointestinal involvement. The oral ulcers were the first manifestation of the
      disease process in 70% of our patients. Skin lesions, genital ulcers, and
      involvement of the central nervous system and the pulmonary system were less
      frequent in our study. CONCLUSIONS: Although it is difficult to obtain figures as
      to the incidence and prevalence of Behcet's disease in Jordan, the clinical
      manifestations, with a few exceptions, are similar to those in other countries in
      the region.

PMID- 8876288
TI  - Papular-purpuric gloves-and-socks syndrome.
AB  - BACKGROUND AND OBJECTIVE: Papular-purpuric gloves-and-socks syndrome (PPGSS) is a
      recently described dermatosis in which human parvovirus B19 (HPV B19) has been
      implicated as etiologic agent; however, it is suspected that PPGSS may be caused
      by various agents. This study was designed to survey the general characteristics
      of PPGSS and to determine the role of HPV B19 in its etiology. METHODS: We
      analyzed data from 21 patient and examined serum samples from three new cases for
      various viruses. RESULTS: The PPGSS displays a striking uniform clinical pattern.
      Histologic and immunofluorescence findings are non-specific. Seroconversion of
      HPV B19 was reported in six cases and confirmed in two of our patients. In only
      one case was a possible causative role of Coxsackie virus B6 suggested
      consistently. CONCLUSIONS: The PPGSS represents a distinctive dermatosis and a
      manifestation of HPV B19 infection. Unlike erythema infectiosum, anti-HPV B19
      antibodies seem to develop later after onset of the skin eruption and while
      viremia is still present.

PMID- 8876289
TI  - Skin disease and socioeconomic conditions in rural Africa: Tanzania.
AB  - BACKGROUND: Many skin diseases in developing countries are associated with
      socioeconomic factors. It is generally agreed that a public health approach to
      dermatology in this setting is particularly appropriate; but, there has been
      little epidemiologic research done to examine which particular socioeconomic
      factors are important determinants of the prevalence of skin disease. This is
      especially true in sub-Saharan Africa. METHODS: A survey of two villages in Ngara
      district, North West Tanzania, involved 254 randomly selected households using a
      questionnaire, measurements of houses and water quality, and examination of the
      skin of 1114 household members. RESULTS: Significant skin disease was encountered
      in 300 individuals (26.9%). Transmissible diseases comprised the bulk of skin
      disease (73.9%) with younger age groups being affected most. Socioeconomic
      conditions were poor, with low quality, crowded housing, low levels of literacy,
      unsatisfactory water sources, and few households with a regular cash income.
      Household density was significantly associated with transmissible skin disease.
      Other indicators of poverty (e.g., no regular cash income and illiteracy) did not
      correlate with the prevalence of skin disease. CONCLUSIONS: Skin disease as
      highly prevalent in the villages surveyed, especially transmissible diseases in
      the younger age groups. Household density was the only socioeconomic factor
      significantly associated with skin disease. Reduction of household density is an
      attainable intervention that could reduce the prevalence of skin disease in rural
      African populations. Simple studies like this one should be the first step in
      community dermatology, assessing the burden of skin disease in communities and
      looking for particular factors with which public health interventions could
      effectively reduce the prevalence of skin disease.

PMID- 8876290
TI  - Skin disease in rural Tanzania.
AB  - BACKGROUND: Skin disease is a common problem, accounting for significant
      morbidity in developing countries. Knowledge about the prevalence of different
      skin conditions allows appropriate planning for provision for these health needs.
      There are currently few data about the needs in rural areas; therefore, this
      study was set up to investigate skin abnormalities found in a village population
      in Tanzania. MATERIALS AND METHODS: A village with a population of 2,876 was
      chosen and one-third of the population was examined for cutaneous abnormalities.
      RESULTS: During the survey, 97.7% of the target population was examined. Signs of
      nutritional deficiency were common with koilonychia affecting 18.1% of the
      population examined and signs of hypoproteinemia being present in 3.4% of them.
      Infections and infestations were also frequently seen. Scabies was observed in
      6.0% and pediculosis capitis in 5.3%. Dermatophyte infection was present in 5.1%.
      These were all most common in prepubertal children. Leg sores were seen in 5.1%
      and leg ulcers in 3.0% of the population. CONCLUSIONS: The survey reveals that
      easily treatable skin infections and infestations are common in a rural Tanzian
      population. Signs of nutritional deficiency are also frequently seen.

PMID- 8876291
TI  - Chloracne in the 1990s.
AB  - BACKGROUND: Chloracne is a disease associated with toxicity of halogenated
      compounds used in some industrial processes. A patient affected by chloracne led
      us to study a total of nine cases from a single factory. METHODS: We studied the
      clinical features of nine patients exposed chronically to chlorobenzenes. On all
      of them blood samples were drawn and biopsies of affected skin and liver were
      taken. Their work environment was visited and studied. RESULTS: All nine patients
      were men and had polymorphic skin lesions, characterized mainly by comedones and
      cysts. They had chronic conjunctivitis and seven had cysts in the Meibomian
      glands. All of them had polyneuropathy and liver damage and seven had
      hypertriglyceridemia. Compounds known to cause chloracne were found in
      exceedingly high concentrations in the water used in the workplace. CONCLUSIONS:
      Every patient exposed to halogenated compounds with the cutaneous manifestations
      of chloracne should be carefully investigated for systemic complications (such as
      ophthalmic, neuropathic, hepatic, and lipoprotein abnormalities).

PMID- 8876292
TI  - Disseminated cryptococcosis presenting as molluscum-like lesions as the first
      manifestation of AIDS.

PMID- 8876293
TI  - Multiple painful keratoacanthomas.

PMID- 8876294
TI  - Neutrophilic eccrine hidradenitis in an HIV-infected patient.

PMID- 8876295
TI  - Papular mucinosis associated with human-immunodeficiency-virus infection.

PMID- 8876296
TI  - Linear and whorled nevoid hypermelanosis in a boy with mental retardation and
      congenital defects.

PMID- 8876297
TI  - Sclerodermatous changes of chronic graft-versus-host-disease treated with puva.

PMID- 8876298
TI  - Dyskeratosis congenita in an ethnic Chinese girl.

PMID- 8876299
TI  - Subungual nodule as manifestation of multiple myeloma.

PMID- 8876301
TI  - Herpes zoster: treatment with Clinacanthus nutans cream.

PMID- 8876300
TI  - Amyopathic dermatomyositis associated with malignancy.

PMID- 8876302
TI  - Econazole 1% shampoo versus selenium in the treatment of tinea versicolor: a
      single-blind randomized clinical study.

PMID- 8876303
TI  - Treatment of skin aging with topical estrogens.
AB  - BACKGROUND: The coincidence of climacteric symptoms and the beginning of skin
      aging suggests that estrogen deficiency may be a common and important factor in
      the perimenopausal woman. Often hormones have been considered important in
      endogenous aging of the skin, but their role has not been clearly defined.
      Therefore, we investigated, whether topical treatment of the skin with estrogen
      could reverse some of the changes in the aging skin. MATERIAL AND METHODS: The
      effects of 0.01% estradiol and 0.3% estriol compounds were compared in 59
      preclimacteric women with skim aging symptoms. Monthly determinations of
      estrodiol (E2), follicle-stimulating hormone (FSH), and prolactin (PRL) were done
      and the monthly clinical monitoring was supplemented by measurements of skin
      hydration by corneometry and profilometry. In 10 patients, skin biopsies were
      taken for immunohistochemical determination of collagen types I and III. RESULTS:
      After treatment for 6 months, elasticity and firmness of the skin had markedly
      improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both
      groups. Furthermore, skin moisture had increased and the measurement of wrinkles
      using skin profilometry, revealed significant, or even highly significant,
      decreases of wrinkle depth in the estradiol and the estriol groups, respectively.
      On immunohistochemistry, significant increases of Type III collagen labeling were
      combined with increased numbers of collagen fibers at the end of the treatment
      period. As to hormone levels, only those of PRL had increased significantly and
      no systemic hormonal side effects were noted.

PMID- 8876304
TI  - Whither dermatology?

PMID- 8876305
TI  - The golden rule of health care: he who has the gold makes the rule.

PMID- 8876306
TI  - Drug reactions in patients with acute HIV infection.

PMID- 8876307
TI  - Photosensitivity and autoantibodies to Sm, Ro, and La in a patient with
      silicosis.

PMID- 8876308
TI  - Epidermal changes are not unusual in lupus erythematosus profundus.

PMID- 8876309
TI  - Allergic contact dermatitis from leather strap of wrist watch.

PMID- 8876310
TI  - HLA-associated susceptibility to chronic onychomycosis in Brazilian Ashkenazic
      Jews.

PMID- 8876311
TI  - Exfoliative dermatitis and malignant melanoma: coincidence or association.

PMID- 8876312
TI  - Intralesional chloroquine for the treatment of cutaneous sarcoidosis.

PMID- 8876313
TI  - Tinea versicolor with generalized anhidrosis.

PMID- 8876314
TI  - The distinction between lacerations and cuts in ligaments and tendons.
AB  - In contrast to skin wounds the characteristic forensic features of lesions of
      ligaments and tendons have rarely been investigated. However, in a suspected
      homicide the question became crucial whether an isolated discontinuity of the
      posterior atlanto-occipital membrane was caused by a rupture mechanism or by a
      cut. In order to reevaluate the associated criteria experimental lesions were
      made in ligaments and tendons and examined histologically. From these experiments
      the following criteria could be established: Lacerations exhibit complete
      destruction of the tissue texture with microruptures and splitting of fibres in
      the adjacent region. Such would edges have an irregular structure and fibres near
      the rupture site exhibit variable thicknesses due to traction. Incisions exhibit
      smooth wound edges with no disturbance of the tissue texture. The thickness of
      fibres near the rupture site is regular. These results were obtained by light
      microscopical examination and confirmed using electron microscopy. Under
      controlled experimental conditions the forces necessary to rupture tendons with a
      diameter of 1 mm varied between 50-70 Newton (N). In the suspected homicide, the
      lesion of the posterior atlanto-occipital membrane was examined visually and
      histologically and was compared with the experimentally established criteria.
      Based on these criteria the lesion could be identified as an incision which had
      probably been caused accidentally while severing the medulla during the first
      autopsy and was therefore not connected with the cause of death.

PMID- 8876315
TI  - French Caucasian population data obtained from fluorescently detected HUMvWFA31/A
      and HUMF13A01 short tandem repeat loci.
AB  - Allele and phenotype frequencies for two tetranucleotide STR (short tandem repeat
      or microsatellite) systems, HUMvWFA31/A and HUMF13A01, were obtained from a
      sample of approximately 240 unrelated individuals randomly selected from the
      French Caucasian population. PCR (polymerase chain reaction) products were
      analysed on 6% polyacrylamide denaturing gels and visualized using fluorescently
      labelled primers on the automated 373A ABI DNA sequencer (Applied Biosystems
      Inc.). French Caucasian allele frequencies were compared to other published
      Caucasian data. Conditions were optimised for the quadruplex PCR amplification of
      these two STR loci together with the HUMFESFPS and HUMTH01 loci and the
      quadruplex PCR was also performed on various forensic DNA samples.

PMID- 8876316
TI  - The forensic value of the immunohistochemical detection of oestrogen receptors in
      vaginal epithelium.
AB  - This study investigated whether oestrogen receptors can be immunohistochemically
      detected in paraffin-embedded vaginal mucosa samples using monoclonal antibodies
      and whether the method would be suitable for the identification of vaginal cells
      in cytological smears. Samples of vaginal mucosa were obtained from living
      females and female corpses, as vaginal smears. For comparison purposes, resected
      prepuce samples and samples of postmortem male urethral mucosa were also
      investigated. Nuclear oestrogen receptors could be regularly detected in the
      basal, parabasal and deeper intermediate epithelium layers of freshly fixed
      vaginal mucosa but proved to be highly sensitive to autolytic changes. In the
      cytological smears obtained from living subjects, no oestrogen receptors were
      detectable. Oestrogen receptors were also detected in the basal epidermal cells
      of the male prepuce.

PMID- 8876318
TI  - Induction of apoptotic cell death in rat thymus and spleen after a bolus
      injection of methamphetamine.
AB  - We examined whether methamphetamine (MAP) induced apoptotic cell death in vivo.
      Male Wistar rats were injected intraperitoneally with 25 mg MAP/Kg body weight
      and were sacrifice at 4, 8 and 24 h. As early as 4 h after a single dose of MAP,
      DNA ladder bands representing DNA fragmentation into multiples of the
      internucleosomal DNA length of about 180 by were observed by gel electrophoresis
      in thymic and splenic DNA. DNA from control rats injected with 1 ml physiological
      saline/Kg body weight showed no ladder band patterns. The proportion of
      fragmented DNA from the thymus increased in a time-dependent manner up to 8 h and
      faint ladder band patterns were observed at 24 h, indicating that cell death via
      apoptosis occurred at an early stage and then apoptotic bodies were scavenged.
      DNA fragmentation in the thymus and spleen induced with MAP was also confirmed by
      the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) method in situ. In control thymus samples, stained cells were numerous in
      the cortex but sparse in the medulla. At the boundary area between the cortex and
      medulla, stained cells were seen as a layer. In the MAP-treated rats, stained
      cells were increased and dispersed equally in the cortex and medulla. In control
      spleen samples, stained cells were numerous in all areas excluding the germinal
      centers. Cells at the germinal centers were stained intensively in MAP-treated
      rat spleen. Light microscopical analyses allowed us to identify lymphocytes
      during the course of apoptotic cell death. Electron microscopic studies showed
      morphological landmarks for the process of cellular apoptosis in both organs e.g.
      lymphocytes with chromatin condensed into crescents at the periphery of the
      nuclei and apoptotic bodies. These result indicate that MAP induced cell death of
      the thymic and splenic lymphocytes via apoptosis.

PMID- 8876317
TI  - A new method of STR interpretation using inferential logic--development of a
      criminal intelligence database.
AB  - A short tandem repeat (STR) system consisting of seven multiplexed loci has
      recently been introduced in the UK to support a National strategy to create large
      DNA databases for criminal intelligence purposes. The process uses automated
      sequencers, employing dye-labelled primers. Identification of tetrameric loci
      such as HUMTH01 are straightforward. Sizing windows are estimated by running a
      series of control allelic ladders on several gels and 'unknown' samples are
      designated if they fall within a defined window. However, utilisation of complex
      STRs (eg. D21S11) characteristically have common variants which differ by just 2
      bp. In addition, rare alleles are encountered which may differ by just 1 bp from
      a common variant. To assist with the identification of alleles, we have
      introduced a series of allelic ladders, so that direct comparisons with 'unknown'
      samples can be made on the same gel. To designate an allele, it should be within
      0.5 bp of an allelic ladder marker. Not all alleles (in particular rare alleles)
      can be included within an allelic ladder, however their expected positions can be
      easily calculated by reference to existing alleles in the ladder. Measurement of
      band shift is also a useful diagnostic tool. A series of guidelines are described
      to enable reliable allelic identification. These guidelines can be converted into
      computer programmes which form the basis of an expert system.

PMID- 8876319
TI  - Macrophage subtyping in the determination of age of injection sites.
AB  - Determination of the age of injection marks in skin may be of particular interest
      in the investigation of drug abuse-related fatalities. The aim of our study was
      to assess the value of macrophage subtyping by antibody-based markers in the
      determination of the age of injection marks. Immunohistochemical investigations
      were performed with the antibodies Ki-M1P, 27E10, MRP14, MRP8 and 25F9.
      Monocytes/macrophages in acute lesions (several hours to 2 days old) expressed
      proteins detectable with the antibodies 27E10 and MRP14 and showed acute
      erythrophagia. An additional reaction with the antibody MRP8 was seen in lesions
      a few days old. An antigen recognized by the antibody 25F9 was found in tissue
      macrophages, multinucleated giant cells of active granulomas and siderophages.
      The expression of the 25F9 detectable antigen was absent in inactive granulomas
      and siderophages, whereas the macrophages were always detectable with the pan
      macrophage marker Ki-M1P.

PMID- 8876320
TI  - Analysis of the STR loci HUMF13A01, HUMFXIIIB, HUMLIPOL, HUMTH01, HUMTPOX and
      HUMVWFA31 in a Japanese population.
AB  - Population studies on six short tandem repeat loci, HUMF13A01, HUMFXIIIB,
      HUMLIPOL, HUMTH01, HUMTPOX and HUMVWFA31 were carried out in a sample of
      unrelated Japanese individuals (n = 337-545) living in Gifu Prefecture (central
      region of Japan). Five alleles could be identified for HUMFXIIIB, six for
      HUMF13A01, HUMLIPOL, HUMTH01 and HUMTPOX, and eight for HUMVWFA31. For all/six
      loci no deviations from the Hardy-Weinberg equilibrium hypothesis were detected.
      The mean exclusion chance ranged from 0.22 to 0.60, the power of discrimination
      from 0.63 to 0.93, and the expected heterozygosity from 0.43 to 0.80. Allele
      frequency distributions for the loci in the Japanese sample were not similar to
      those in samples from other racial or ethnic groups except for the Chinese (for
      HUMTPOX). The results demonstrate that HUMTH01, HUMTPOX and HUMVWFA31 are more
      useful for forensic investigations in the Japanese population that the other
      three loci.

PMID- 8876321
TI  - E. coli endotoxin enhances cardiomyopathy in rats with chronic alcohol
      consumption.
AB  - The purpose of the study was to show whether it was possible to produce alcoholic
      cardiomyopathy by short-term alcohol ingestion combined with an infinitesimally
      low endotoxin injection. Wistar rats were fed an alcoholic liquid diet according
      to the formula of Lieber and Decarli, and challenged with an injection of E. coli
      lipopolysaccharide (LPS) endotoxin (1.0 microgram/g body weight per day for ten
      weeks). After ten weeks alcohol diet combined with LPS challenge, light
      microscopical examination showed changes commonly seen in alcoholic
      cardiomyopathy such as hypertrophy, oedema and disarray of myofibers. By electron
      microscopy, degeneration of mitochondria and degeneration of myocardial fibers
      were observed, the latter showing disturbance of the myofibrilla arrangement and
      interstitial fibrosis. Rats on an alcoholic liquid diet and rats challenged with
      a single identical doses of LPS did not show characteristic histological findings
      of alcoholic cardiomyopathy. These results suggest that short-term alcohol
      ingestion combined with an infinitesimally low endotoxin injection experimentally
      produces alcoholic cardiomyopathy, and may support the idea that endotoxin plays
      an important role in the aetiology of alcoholic cardiomyopathy.

PMID- 8876322
TI  - A case of drowning linked to ingested sulfides--a report with animal experiments.
AB  - An adult male was found dead beneath a pool of sewage in the pump room of a fish
      market. Autopsy revealed the cause of death to be suffocation after aspirating
      sewage into the respiratory tract. Since hydrogen sulfide gas was detected in the
      atmosphere at the scene of the accident, gas poisoning was suspected and
      toxicological analysis of sulfides in body tissues was performed. The
      concentrations of sulfides in the blood, lung and kidney were 0.95 mumol@ml, 0.22
      and 0.38 mumol/g, respectively. These values were remarkably higher than those in
      previously reported cases involving exposure to hydrogen sulfide gas. Therefore,
      oral intake of sulfides was assumed and the distribution of sulfides in tissues
      following oral administration of sodium sulfide solution was examined by means of
      animal experiments using rats. The concentration of sulfides in the blood from
      rats following oral intake was much higher than that seen following gas exposure.
      Based on these results, we concluded that the victim had been exposed to hydrogen
      sulfide gas and had then collapse into a pool of sewage containing sulfides. The
      sulfides which were distributed throughout the body tissues had mainly issued
      from the alimentary tract prior to death by drowning.

PMID- 8876323
TI  - Population genetic study of the AmpFLP system APO B in an Austrian population
      sample.
AB  - Allele frequencies of the AmpFLP system APO B were determined in an Austrian
      population sample consisting of 210 unrelated Caucasian individuals living in the
      Salzburg region. A total of 25 different alleles could be observed. The allele
      distributions were in accordance with Hardy-Weinberg equilibrium. No new
      mutations were found in 184 meioses and seven "interalleles" and four alleles <
      29 could be detected.

PMID- 8876324
TI  - Evaluation of 7 DNA markers (D1S80, HLA-DQ alpha, LDLR, GYPA, HBGG, D7S8 and GC)
      in a Japanese population.
AB  - A Japanese population was tested for the 7 DNA markers D1S80, HLA-DQ alpha, low
      density lipoprotein receptor (LDLR), glycophorin A (GYPA), hemoglobin G
      gammaglobin (HBGG), D7S8 and group specific component (GC). Each of these 7
      markers was found to be useful for paternity testing and individual
      identification in a Japanese population.

PMID- 8876325
TI  - Forensic evaluation of HUMCD4: an Italian database.
AB  - The YTTTC pentanucleotide short tandem repeat polymorphism HumCD4 was studied in
      an Italian population sample. PCR products were compared to an allelic ladder by
      manual PAGE and silver staining. A total of 6 alleles ranging from 5 to 12
      repeats were represented in the analysed sample, of which 3 alleles (10, 6 and 5
      repeats) were predominant and displayed a combined frequency of 0.91. Successful
      amplification was obtained from different sources such as blood and urine stains,
      teeth and paraffin embedded tissues. Results were also determined in cases of
      severely degraded DNA. We consider that the HUMCD4 polymorphism may be a useful
      tool for individual identification, paternity testing, population studies and
      have also employed this locus to monitor engraftment of bone marrow
      transplantation.

PMID- 8876326
TI  - Phallus, penis and mental space.
AB  - In this paper the author suggests that it is insufficient simply to make a
      distinction, as Laplanche & Pontalis do, between penis to denote the male organ
      in its bodily reality and phallus to describe the symbolic aspect. She suggests
      that there is an important symbolic function for which the word phallus is not
      appropriate and which she calls penis-as-link. She suggests that it is the
      introjection of the penis-as-link which has a structuring function and promotes
      mental space and thinking, in that it recognises the full oedipal situation
      including the parental relationship (and mental bisexuality). With clinical
      material she shows that the lack of internalisation of the penis-as-link leads to
      the search for the phallus as a fantasy and she illustrates the relationship
      between the internalisation of the penis-as-link and mental space and thinking.

PMID- 8876327
TI  - The concept of psychic reality--how useful?
AB  - The author argues that Freud coined the phrase 'psychic reality' to indicate how
      neurotic patients and others treat unconscious psychic concepts and fears as if
      they were real. They respond to the challenges of everyday life not in terms of
      objective reality, but rather in keeping with their inner 'psychic' reality. With
      the development of different schools of thought in psychoanalysis, opinions as to
      precisely what constitutes the contents and character of unconscious mental
      functioning differ enormously, to the extent that there is no general agreement
      as to the nature and quality of unconscious mental elements. Psychoanalysts do
      not have a shared view of what constitutes psychic reality, with the result that
      genuine scientific interchange has become increasingly difficult and attenuated.
      The author considers that what is required is the exploration and enunciation of
      an agreed upon methodological approach to the interpretation of clinical data and
      thence to the formulation of mutually acceptable psychoanalytic concepts.

PMID- 8876328
TI  - 'Listening to listening'.
AB  - The author links the function of analytic listening to Freud's concept of
      Nachtraglichkeit, which she defines as the retroactive assignment of meaning
      rather than mere deferred action, and derives the notion of 'listening to
      listening' from their combination. A dialectical conception of time is proposed,
      with interpretation involving three logical phases, respectively incumbent on the
      analyst, on the patient and on both. Two clinical examples are given, showing how
      the patient speaks and listens from a position dictated by his unconscious
      identifications, which also cause him to reinterpret the analyst's
      interpretations and his silences. By listening to the patient's reassignment of
      meaning to his interpretations, the analyst can discover the patient's
      unconscious identifications and, together with the patient, thereby facilitate
      the process of psychic change. The author contends that by the function of
      'listening to listening' it is possible to overcome the dilemma of whether the
      analyst with his interpretation or the patient with his own reinterpretation of
      it is right.

PMID- 8876329
TI  - 'How can we know the dancer from the dance?': hyperbole in hysteria.
AB  - In this paper the author discusses histrionic or hyperbolic behaviour, which she
      regards as specific to a certain type of hysterical character. Histrionic
      hysteria she sees as a pathological organisation. With the use of two clinical
      examples she examines the phenomenon of hyperbole or exaggeration and suggests
      that they convey a picture of the patient's internal objects and his relationship
      to them. Exaggeration can also be used by the patient to distance himself from
      what is going on in his mind and yet to make the object--the analyst in the
      session--aware of unrecognised emotions. To study hyperbolic behaviour the author
      constructs a model in which she divides manifestations of this type of behaviour
      into three parts; 'the observing self, the acting self and the audience' and
      examines the different identifications that are at the basis of each part. She
      considers that these areas of the personality encapsulate fragmenting processes
      that are continually active and threatening the patient. An exploration of this
      division into three areas should facilitate and deepen understanding of the
      processes involved in histrionic behaviour.

PMID- 8876330
TI  - Learning theory and intrapsychic conflict.
AB  - This paper is one in a series (Gillett, 1990, 1994) attempting to explore the
      implications of modern ideas about learning for psychoanalytic theories of
      treatment and pathogenesis. The key concept is that of learned expectations,
      which establishes links with Freud's 1926 theory of neurotic anxiety as caused by
      the expectation of danger. The new understanding of classical Pavlovian
      conditioning entails changes in the basic theory of intrapsychic conflict
      described in previous papers (1990, 1994). The relationship of learning theory to
      Freud's 1926 theory of intrapsychic conflict has received insufficient attention
      in the psychoanalytic literature because of insufficient familiarity with the
      repudiation of behaviourism by psychologists in favour of a representational
      theory of the mind.

PMID- 8876331
TI  - Subjectivity and intersubjectivity of clinical facts.
AB  - The author has learned a great deal from the IJPA 75th Anniversary Issue,
      particularly regarding ways in which psychoanalysts across the world are
      consensually re-defining psychoanalysis as a quintessentially subjective and
      intersubjective endeavour. In summarising her response to the Issue, she
      addresses the ways in which its focus on psychoanalytic subjectivity and
      intersubjectivity helps to define the nature of psychoanalysis as a scientific
      endeavour. In addition, she identifies an area that she wished had been more
      developed in the Issue: some further specification of the cognitive and
      communicative processes that make for psychoanalytic subjectivity and
      intersubjectivity. She speculates that, as we continue our attempts further to
      understand those processes, we may find it valuable to look towards a body of
      research that is absent from consideration in the 75th Anniversary Issue (and is,
      for that matter, absent from serious and scientific consideration by
      psychoanalysts in general): research on mental effects currently considered
      'anomalous', or outside the bounds of conventionally defined human mental
      function and capacity. She describes briefly some of that research in the context
      of its possible relevance to issues of psychoanalytic subjectivity and
      intersubjectivity. She takes up the specific relevance of that research to
      phenomena we have traditionally subsumed under categories of experience like
      intuition, empathic attunement and unconscious communication.

PMID- 8876332
TI  - My experience of analysis with Fairbairn and Winnicott. (How complete a result
      does psychoanalytic therapy achieve?) 1975.

PMID- 8876333
TI  - The case of Harry Guntrip.
AB  - The author describes Harry Guntrip (1901-1975), who was well known for his
      expositions of psychoanalytic theory. His personal symptoms had led him to seek
      psychoanalytic help. Before his death he wrote an account of his analysis with
      Fairbairn and his psychotherapeutic sessions with Winnicott. Both of them had
      helped him but not cured his basic problems. The author argues from Guntrip's own
      accounts that he reached a deep unconscious resistance to the process of
      analysis, as Fairbairn believed, and that Winnicott came near to interpreting the
      source of this resistance. Freud's paper of 1917 on anal erotism is used to
      suggest an approach by which it might have been interpreted and analysed.

PMID- 8876334
TI  - Some personal recollections and impressions of Harry Guntrip.
AB  - Harry Guntrip will be known to most readers, and a generation of students, as the
      author of 'Personality Structure and Human Interaction', and of 'Schizoid
      Phenomena, Object Relations and the Self'. These books are still an extremely
      clear and well argued presentation of the development of psychoanalytic theory.
      The first was an enormous labour of digesting, criticising and organising all the
      major psychoanalytic contributions into a theoretical whole that was a statement
      of faith by the author. The second linked some of the papers that continuously
      flowed from him throughout life. Both are a witness to his drive and his
      intellect. This paper is a memoir of almost thirty years' friendship, and shows
      something of the man and the therapist who made the books possible. It gives some
      picture of his life, his personality and his problems with health. In conclusion
      Guntrip's paper on his analysis with Fairbairn and Winnicott is discussed. The
      author considers that Guntrip's forte, an understanding of the schizoid problem,
      has its roots in a personal limitation revealed in his experience of analysis. He
      needed to be in intellectual control, and had great difficulty in emotional
      letting go.

PMID- 8876335
TI  - Transference and countertransference in the analysis of a child with autistic
      nuclei.
AB  - The author stresses the importance of using the countertransference when working
      with autistic and borderline children, in whom severe disorders of cognitive and
      emotional development have not permitted the establishment of an internal three
      dimensional space whereby emotions can be contained, meaning can be assigned to
      those emotions and symbols can be formed. She argues that the transference will
      arise gradually in response to the analyst's countertransference. Great
      importance is attached to the setting in both its material and psychic aspects,
      the stability of the former being essential because of the patient's two
      dimensional mode of functioning, in which he lacks any representation of space
      and time. After a review of the theoretical background to the treatment of
      autistic children with particular reference to the work of Houzel and Tustin and
      a brief discussion of general aspects of the transference in the light of the
      views of Freud, Klein and Bion, the author turns to the clinical material proper,
      presenting vignettes from a number of sessions in the analysis of an autistic
      boy. These show how she utilises her own emotions, sensations and associations to
      gain information about the patient's state and, by assigning meaning to these
      manifestations and communicating it to him, to impart motion to his frozen
      internal world. The author reports that, after several years of analysis, the
      patient has introjected a stable object that will lead to healthier development
      and a sense of security.

PMID- 8876336
TI  - Fixation of asthma and sexual impotence at different pregenital stages.
AB  - Most psychoanalytic writers believe that both asthma and sexual impotence depend
      on fixations at the early stages of the Oedipus complex. Through psychoanalytic
      study of patients with both disorders, the author believes that this problem may
      be considered from another angle whereby the fixation of sexual impotence is
      situated at the early stages of the Oedipus complex, while asthma depends on
      fixations at the level of the breast although its character is also triangular.
      It is the author's opinion that in studying the psycho-pathogenesis of these
      afflictions it is important to distinguish between basic and defensive
      phantasies, since it is the former which reveals the level of object relations
      where the malady is situated. Defensive phantasies include, owing to regressive
      and progressive movements, objects and defences from other levels and therefore
      cannot be used for the investigation of levels of fixation. In the cases
      presented, the aim of the psychosomatic symptom is, in asthma, to avoid the
      collapse of the self while, in impotence, it is to avoid castration anxieties,
      when the introjected object does not provide sufficient cohesion to the self or
      is experienced as persecutory. At first the patient uses manic defences but
      should these fail, further defences are resorted to (contraction of the
      bronchioles in asthma and inhibition in sexual impotence), and these give rise to
      the psychosomatic symptom.

PMID- 8876337
TI  - The fate of training cases.
AB  - The authors regard the treatment of analytic patients as a crucial, formative and
      ultimately integrative experience in a candidate's development that has received
      remarkably little direct attention as an aspect of analytic education. From 1983
      to 1992 a questionnaire was sent to all graduates of the Columbia University
      Psychoanalytic Center for Training and Research asking for information on
      training cases, both those terminated before graduation and those still ongoing
      at the time of graduation. The authors report data on pre-graduation candidate
      case experience, treatment duration of training cases, the impact of graduation
      on the course of analysis and on a global assessment of the outcome. 70 per cent
      of the 71 who graduated between 1983 and 1992 returned the questionnaire. The
      survey showed that before graduation the average candidate had a cumulative nine
      year experience of treating training cases. 35 per cent of cases terminated
      before graduation and were invariably considered to have an unsuccessful outcome.
      Thus the 'failed case' was a common event and should be anticipated as part of a
      candidate's education. There was no evidence of precipitous termination of cases
      after graduation; in fact the data suggest that graduation has no discernible
      effect on the timing of termination. The vast majority of candidates at Columbia
      continue to be supervised after graduation, which suggests that graduation is
      only a marker in the training of an analyst, rather than the point of completion.
      With respect to outcome, 23 per cent of the 151 terminated cases were rated
      successful. Though this finding is consistent with previous reports, the
      methodological limitations of this study limit the confidence in this result. One
      of the important issues raised by these results is the impact of training
      requirements on the candidate's education and the Fate of Training Cases.

PMID- 8876338
TI  - The multiple functions of the supervisor: a summary of the seventh IPA conference
      of training analysis.

PMID- 8876339
TI  - Panel report: History of psychoanalysis on the West Coast.

PMID- 8876341
TI  - The effect of oral creatine monohydrate supplementation on running velocity.
AB  - Creatine supplementation has been shown to augment muscle PCr content and
      increase the rate of ATP resynthesis. Thus, we hypothesized that creatine
      supplementation might enhance sprinting performance. Eighteen subjects completed
      both of two testing sessions (control and postsupplement) 1 week apart, wherein
      they sprinted three 60-m distance trials that were recorded with videotape.
      Following the control session, for 7 days, subjects in the treatment group
      ingested a creatine-glucose mixture, while the placebo group consumed a glucose
      powder, followed by the postsupplementation session. Velocities of the subjects
      through three testing zones within the 60-m sprint were calculated from the
      videotape. Resultant velocities were analyzed using a MANOVA with a 2 x 2 x 3 x 3
      (Group x Session x Trial x Zone) design. Results indicated that there were no
      statistically significant main or interaction effects on velocity between groups
      for session, trial, or zone. These data do not support the hypothesis that
      supplementary creatine ingestion will enhance velocity during the early or latter
      segments of a 60-m sprint.

PMID- 8876342
TI  - Effect of oral creatine supplementation on single-effort sprint performance in
      elite swimmers.
AB  - Oral supplementation with creatine monohydrate (Cr.H2O) has been reported to
      increase muscle creatine phosphate levels. The aim of the present study was to
      determine the effect of such supplementation on performance of a single-effort
      sprint by elite swimmers. Thirty-two elite swimmers (M = 18, F = 14; age = 17-25
      years) from the Australian Institute of Sport were tested on two occasions, 1
      week apart. Tests performed were 25-m, 50-m, and 100-m maximal effort sprints
      (electronically timed with dive start, swimmers performing their best stroke),
      each with approximately 10 min active recovery. A 10-s maximal leg ergometry test
      was also undertaken. Swimmers were divided into two groups matched for sex,
      stroke/event, and sprint time over 50 m, and groups were randomly assigned to 5
      days of Cr.H2O supplementation (4 . day-1 x 5 g Cr.H2O + 2 g sucrose, n = 16) or
      placebo (4 . day-1 x 5 g Polycose + 2 g sucrose, n = 16) prior to the second
      trial. Results revealed no significant differences between the group means for
      sprint times or between 10-s maximal leg ergometry power and work. This study
      does not support the hypothesis that creatine supplementation enhances single
      effort sprint ability of elite swimmers.

PMID- 8876343
TI  - Effects of ingesting supplements designed to promote lean tissue accretion on
      body composition during resistance training.
AB  - This study examined the effects of ingesting nutritional supplements designed to
      promote lean tissue accretion on body composition alterations during resistance
      training. Twenty-eight resistance-trained males blindly supplemented their diets
      with maltodextrin (M), Gainers Fuel 1000 (GF), or Phosphagain (P). No significant
      differences were observed in absolute or relative total body water among groups.
      Energy intake and body weight significantly increased in all groups combined
      throughout the study with no group or interaction differences observed. Dual
      energy x-ray absorptiometry-determined body mass significantly increased in each
      group throughout the study with significantly greater gains observed in the GF
      and P groups. Lean tissue mass (excluding bone) gain was significantly greater in
      the P group, while fat mass and percent body fat were significantly increased in
      the GF group. Results indicate that total body weight significantly increased in
      each group and that P supplementation resulted in significantly greater gains in
      lean tissue mass during resistance training.

PMID- 8876344
TI  - Nutritional status and lipid profiles of trained steroid-using bodybuilders.
AB  - Fourteen trained male anabolic steroid-using bodybuilders (SBBs) (19-41 years)
      were recruited for the study. Three-day diet records were obtained from SBBs and
      analyzed. A resting venous blood sample was drawn, and serum/plasma was
      subsequently analyzed for various nutritionally related factors. Results showed
      that mean dietary energy (4,469 +/- 1,406 kcal), protein 252 +/- 109 g), and
      vitamin and mineral intakes of SBBs greatly exceeded U.S. Recommended Dietary
      Allowances. Dietary cholesterol intake was 2.8 times the recommended levels. Mean
      serum/plasma nutrient concentrations of SBBs were within normal range. However,
      individual SBBs had a number of serum/plasma values outside of the normal or
      recommended range, the most notable of which was hypercalcemia, which was present
      in 42% of SBBs. Serum/plasma lipids were such as to increase the risk of
      cardiovascular disease in these subjects.

PMID- 8876345
TI  - Comparison of Eating Disorder Inventory (EDI-2) scores of male bodybuilders to
      the male college student subgroup.
AB  - The intensity and effort of bodybuilding training suggest an overinvestment in
      body shape and physical appearance, which has been suggested to be a risk factor
      for developing eating disorders. The purpose of this study was to investigate the
      prevalence of eating disorder tendencies among a sample of collegiate male
      bodybuilders (BB, n = 68) and controls (C, n = 50) (nonbodybuilders), using the
      Eating Disorders Inventory 2 (EDI-2). T tests were used to test the hypothesis
      that bodybuilders' scores would be higher than those of controls. The mean scores
      on the EDI-2 did not indicate the presence of eating disorder tendencies for
      either group. Controls scored significantly higher than bodybuilders on the Body
      Dissatisfaction scale. Results indicate that when the EDI-2 is used, college-age
      male bodybuilders are not shown to be more likely to have eating disorders than a
      group of college-age male controls.

PMID- 8876346
TI  - No ergogenic effect of ginseng ingestion.
AB  - The purpose of this study was to examine the effects of ginseng extract ingestion
      on physiological responses to intense exercise. Subjects performed a control ride
      (CN) on a cycle ergometer, followed by placebo (PL) and ginseng (GS) treatments.
      Ginseng was ingested as 8 or 16 mg/kg body weight daily for 7 days prior to trial
      GS. Venous blood was sampled for FFA, lactate, and glucose analyses. Due to
      similar findings for both dose groups, the subjects were considered as one group.
      Lactate, FFA, VO2, VE, and RPE increased significantly from 10 through 40 min.
      RER increased during the first 10 min of exercise and then remained stable, with
      no intertrial differences. Glucose did not vary significantly from 0 to 40 min or
      among treatments. RPE was significantly greater and time to exhaustion was
      significantly less during trial CN than PL or GS, while PL and GS trials were
      similar. The data indicated that with 1 week of pretreatment there is no
      ergogenic effect of ingesting the ginseng saponin extract.

PMID- 8876347
TI  - Diet and muscle glycogen concentration in relation to physical performance in
      Swedish elite ice hockey players.
AB  - The effects of carbohydrate (CHO) loading on physical characteristics including
      muscle fiber distribution, muscle glycogen concentration, and physical
      performance were studied in two top Swedish ice hockey teams. Players were
      randomly allocated to two groups: those consuming a CHO-enriched diet (CHO group)
      and those consuming a mixed diet (controls). Biopsies from the vastus lateralis
      muscle were taken three times: after Game 1, before Game 2, and after Game 2.
      Muscle fiber distribution averaged 50 +/- 2% slow twitch fibers (mean +/- 1 SEM).
      Muscle glycogen concentrations (measured in mmol glucose units . kg-1 wet muscle)
      were as follows: after Game 1, 43 +/- 4 (all players); before Game 2, 99 +/- 7
      (CHO group) and 81 +/- 7 (controls); and after Game 2, 46 +/- 6 (CHO group) and
      44 +/- 5 (controls). Distance skated, number of shifts skated, amount of time
      skated within shifts, and skating speed improved with CHO loading. It was
      concluded that individual differences in performance could be related to muscle
      glycogen metabolism.

PMID- 8876348
TI  - Short-term changes in body composition and metabolism with severe dieting and
      resistance exercise.
AB  - The primary aim was to investigate whether the reduction in resting metabolic
      rate (RMR) and fat free mass (FFM) associated with a short-term very low
      kilojoule diet (VLKD) is altered by concurrent resistance exercise. Twenty
      overweight, premenopausal women were pair matched on body surface area and
      randomly assigned to either diet only (3,400 kJ/day) or diet combined with
      resistance training. Before and after 4 weeks of treatment, RMR was assessed by
      indirect calorimetry; total body mass (TBM), FFM, and fat mass (FM) by dual
      energy x-ray absorptiometry; total body water (TBW) by bioelectrical impedance;
      and strength by a weight-lifting test. Both groups had significantly lower TBM,
      FFM, FM, TBW, absolute RMR, and RMR, with FFM as the covariate, in the posttests
      than the pretests with no significant differences between groups. It was
      concluded that 4 weeks of resistance training did not prevent or reduce the
      decline in FFM and RMR observed with a VLKD.

PMID- 8876349
TI  - Branched-chain amino acid supplementation during repeated prolonged skiing
      exercises at altitude.
AB  - This study was conducted to test the hypothesis that a branched-chain amino acid
      (BCAA) supplementation would minimize changes in body composition and alterations
      in plasma amino acid profile induced by prolonged exercises at altitude. Twenty
      four highly trained subjects participated in six successive sessions of ski
      mountaineering (6-8 hr duration, altitude 2,500-4,100 m). Twelve subjects took a
      dietary supplement of BCAA (BCAA group) and 12 took a dietary supplement that was
      98% carbohydrate (C group). Body weight decreased in C subjects (-2.1%, p < .01),
      while the body weight loss recorded in the BCAA group was not statistically
      significant (-1.2%, NS). Changes in body composition that resulted from repeated
      skiing exercise at altitude were not significantly minimized by BCAA
      administration. Peak power output recorded during an incremental bicycle exercise
      decreased in C subjects but did not change significantly in BCAA subjects.
      Results of this study demonstrate that neither changes in body composition
      related to the ski mountaineering program nor muscular performance during
      isometric contraction was significantly affected by BCAA administration.

PMID- 8876350
TI  - Body weight changes and voluntary fluid intakes during training and competition
      sessions in team sports.
AB  - Fluid losses (measured by body weight changes) and voluntary fluid intakes were
      measured in elite basketball, netball, and soccer teams during typical summer and
      winter exercise sessions to determine fluid requirements and the degree of fluid
      replacement. Each subject was weighed in minimal clothing before and immediately
      after training, weights, and competition sessions; fluid intake, duration of
      exercise, temperature and humidity, and opportunity to drink were recorded. Sweat
      rates were greatest during competition sessions and significantly lower during
      weights sessions for all sports. Seasonal variation in dehydration (%DH) was not
      as great as may have been expected, particularly in sports played indoors.
      Factors influencing fluid replacement during exercise included provision of an
      individual water bottle, proximity to water bottles during sessions,
      encouragement to drink, rules of the game, duration and number of breaks or
      substitutions, and awareness of personal sweat rates. Guidelines for optimizing
      fluid intakes in these three sports are provided.

PMID- 8876351
TI  - Asymptomatic shedding of herpes simplex virus from the genital tract: uncertainty
      and its consequences for patient management. The Herpes Simplex Virus Advisory
      Panel.
AB  - A frequent component of the management of patients with genital herpes concerns
      the possibility of asymptomatic shedding and potential sexual transmission of the
      virus. Approaches intended to provide supportive counselling and reassurance of
      patients about these issues need now to be modified in the light of increasing
      data of the frequency of asymptomatic detection of virus and the effects of
      antiviral therapy on this phenomenon. Further studies to delineate the
      relationship between asymptomatic detection of HSV in the genital tract and the
      mechanism of sexual transmission of this virus need to be conducted before
      clinicians instigate antiviral suppressive treatment primarily to prevent sexual
      transmission of HSV. However, it is important that the new data and our greater
      understanding of the natural history of genital herpes is translated into
      accurate and comprehensible information for our patients.

PMID- 8876352
TI  - Defining bacterial vaginosis: to BV or not to BV, that is the question.
AB  - The history of bacterial vaginosis (BV), now extending over more than 40 years,
      has been remarkable not only in terms of repeatedly changing the name of the
      bacterium that we now know as Gardnerella vaginalis but also in relation to what
      is thought to constitute the condition, what it should be called and how the
      diagnosis can best be made. The composite clinical criteria are often confusing
      for the nonspecialist, provide room for inter-observer error, and
      misinterpretation of just one criterion can lead to considerable over or under
      diagnosis. There is no doubt that diagnosis should be through a Gram-stained
      vaginal smear, allowing detection not only of 'full blown' BV but also patterns
      of vaginal flora that while not in this category are nevertheless abnormal.
      Accurate diagnosis is important in view of the ever-growing list of other
      important conditions that may occur as a consequence of the abnormal flora. In
      addition to this, we raise the question of whether the name and abbreviation BV
      is the best either scientifically or from the point of view of the lay public.
      While recognizing that it now may be too ingrained for further change, is it
      possible to have a better term, at least for lay use?

PMID- 8876353
TI  - AIDS in rural Africa: a paradigm for HIV-1 prevention.
AB  - Networks of concurrent sexual partnerships may be the primary cause of epidemic
      spread of HIV-1 in parts of sub-Saharan Africa. This pattern of sexual behaviour
      increases the likelihood that individuals experiencing primary HIV-1 infection
      transmit the virus to other persons. Networks of concurrent partnerships are
      likely to be important in both the early ('epidemic') and late ('endemic') phases
      of HIV-1 transmission. Interventions should aim to break the sexual networks,
      whatever the stage of the epidemic. However, prevention of transmission in the
      endemic phase also requires a greater awareness of early clinical manifestations
      of HIV-1 infection in the general population. Such awareness, coupled with the
      availability of condoms and access to HIV-1 testing facilities, may reduce
      transmission in discordant couples.

PMID- 8876354
TI  - The management of mycobacterial infections in HIV seropositive individuals.
      Jefferiss Wing Therapeutics and Protocols Group.

PMID- 8876355
TI  - AIDS defining diseases in the UK: the impact of PCP prophylaxis and twelve years
      of change.
AB  - We examined all reports of adult AIDS cases made to the 2 national surveillance
      centres in the UK for changes in AIDS defining conditions between January 1982
      and September 1994. Differences and changes among persons diagnosed since January
      1988 who had and had not been aware of their HIV infection prior to their AIDS
      diagnosis were of particular interest. Pneumocystis carinii pneumonia (PCP) is
      the AIDS defining disease most often reported at the initial AIDS diagnosis. Its
      proportion of all AIDS cases has increased significantly between January 1982 and
      December 1987 and decreased markedly thereafter. Since January 1988 a significant
      decrease in the proportion of cases diagnosed with cryptosporidial infection was
      also observed while increases were observed in the proportion of cases diagnosed
      with: HIV wasting (chi(1)(2) = 5.56) PML (chi(1)(2) = 19.47), mycobacterium avium
      complex (chi(1)(2) = 35.76) and pulmonary tuberculosis (chi(1)(2) = 144.0). For
      cases diagnosed between January 1988 and September 1994, PCP was more likely to
      be diagnosed in patients previously unaware of their HIV infection (P < 0.01) as
      was extrapulmonary TB (P < 0.01). In contrast, the following diseases were more
      likely to be diagnosed in patients already aware of their HIV infection prior to
      the diagnosis of AIDS: oesophageal candidiasis (P < 0.001), HIV wasting (P =
      0.07), mycobacterium avium complex (P = 0.0001), cytomegalovirus disease (P <
      0.001), HIV encephalopathy (P = 0.0009) and cryptosporidial infection (P = 0.02).
      Prophylaxis and anti-retroviral therapy appear to have had a significant impact
      on the temporal changes of the most frequently diagnosed AIDS diseases. While PCP
      prophylaxis has substantially reduced the likelihood of a PCP diagnosis at AIDS,
      the corresponding increase in other opportunistic infections suggests that there
      may be a need for improved prophylaxis for these conditions.

PMID- 8876356
TI  - Clinical features, outcome and survival from cerebral toxoplasmosis in Edinburgh
      AIDS patients.
AB  - Nineteen cases of cerebral toxoplasmosis (CTOX) are reported from a group of
      Edinburgh AIDS patients. All patients were severely immunodeficient at the time
      of presentation with CD4 count < 50 cells/mm3. Thirteen patients had suffered a
      previous AIDS-defining illness. In Edinburgh, CTOX has developed in 48% of
      patients who are seropositive for toxoplasma and have a CD4 count < 50 cells/mm3.
      It is estimated that at least half of the toxoplasma seropositive patients will
      develop CTOX if they survive for 21 months after reaching a time in their illness
      when the CD4 count = 50 cells/mm3. The incidence of CTOX in toxoplasma
      seronegative patients with a CD4 count < 50 cells/mm3 is 1.3%. All patients
      showed improvement on treatment and there was no correlation between clinical or
      radiological features and patient survival. Those patients unable to tolerate
      first choice anti-toxoplasma therapy had a significantly shorter survival than
      the remainder but there was no single therapeutic regimen which conferred a
      survival advantage. Eighteen patients had died at the time of study and the
      median survival following diagnosis of cerebral toxoplasmosis was 10 months
      (range 3-38 months). Postmortem examination of the brain was available in 8, 4 of
      whom had concomitant cerebral lymphoma. The survival from AIDS or CD4 count = 50
      cells/mm3 did not differ significantly between those with treated CTOX and a
      control group who had no toxoplasma infection, suggesting that treatment is
      reasonably effective. CTOX is a disease associated with severe HIV-related
      immunodeficiency and, in those with a CD4 count < 50 cells/mm3, occurs more than
      35 times as frequently in toxoplasma-seropositive than toxoplasma-seronegative
      patients. Treatment is effective but the outcome of treated disease cannot be
      predicted from presenting clinical or radiological features. Concomitant space
      occupying cerebral pathology is evident in 50% of post-mortem examinations.

PMID- 8876357
TI  - HIV infection among pregnant women in Lindi, Tanzania, 1989-1993.
AB  - One obstacle to contain the HIV-1 epidemic in the general population in Africa is
      a lack of knowledge about how it is spread in rural areas. We examined 683
      pregnant women in 1989 and 484 in 1993 who attended antenatal clinics in Lindi
      district, Tanzania to determine changes in the prevalence of HIV-1 in a remote
      area in East Africa. The prevalence rose from 0.44% in 1989 to 8.7% in 1993.
      Women with more than 1 partner (17.25% vs 2.78%), STD patients (42.4% vs 6.2%),
      women from urban areas (10.2% vs 3.57%) and patients younger than 21 years were
      more likely to have HIV antibodies. By logistic regression analysis, 1993 as year
      of testing was associated with the greatest risk for HIV seropositivity (P <
      0.00002) followed by clinical signs of STD (P < 0.00005) and urban residence (P =
      0.0275). Teaching of all women attending antenatal care how to minimize their
      future risk of acquiring HIV is urgently needed as one tool to prevent a fast
      spread of HIV throughout the continent.

PMID- 8876358
TI  - Sexually transmitted diseases: a survey of case management in Malawi.
AB  - A national survey of sexually transmitted disease (STD) case management was
      carried out at 39 health care facilities in Malawi in 1994. Fifty-four health
      care providers were observed managing 150 patients presenting with selected STD
      syndromes and 103 providers were interviewed. STD case management was assessed by
      calculation of WHO/GPA prevention indicators (PIs) from observation data. The
      overall rate for PI-6, which measures correct assessment and treatment of STD
      patients was 11% (81% for history taking, 46% in physical examination, and 13%
      correct antibiotic treatment according to national guidelines). The score for PI
      7, which measures overall patient counselling was 29% (65% for partner
      notification and 40% for condom advice). Although Haemophilus ducreyi is at least
      as common as Treponema pallidum as the causative agent for genital ulcers, only
      16% of patients with genital ulcers were treated effectively for chancroid vs 56%
      for syphilis. Female patients received less comprehensive care than male STD
      patients. Only 20% of STD patients were offered condoms. Overall, the survey
      results support the policy decision to adopt syndromic management of STDs, and
      provide baseline information for planning and evaluation of a national control
      programme.

PMID- 8876359
TI  - Efficacy of inosine pranobex oral therapy in subclinical human papillomavirus
      infection of the vulva: a randomized double-blinded placebo controlled study.
AB  - A randomized double-blind placebo controlled study was carried out to assess the
      efficacy of inosine pranobex (1 g orally 3 times a day for 6 weeks) in the
      treatment of symptomatic subclinical human papillomavirus infection of the vulva.
      In a series of 55 women, 22 patients in the inosine pranobex group and 24
      patients in the placebo group were suitable for analysis. A total of 14 (63.5%)
      of the inosine pranobex treated patients and 4 (16.7%) of the placebo treated
      patients showed significant vulval epithelial morphological improvement (P =
      0.005) at 2 months after initiation of treatment. Whereas 13 (59.1%) and 9
      (37.5%) patients in the respective groups showed significant improvement in the
      severity of pruritus vulvae (P = 0.435). Twelve (66.7%) of 18 patients with
      morphological improvement compared to 10 (35.7%) of 28 patients with no
      morphological improvement experienced significant symptomatic alleviation of
      pruritus vulvae (P = 0.041). Similar results were seen at the second assessment 4
      months after the initiation of treatment. Adverse drug reactions were reported by
      2 patients in the treatment group and by 2 patients (skin rash) in the placebo
      group. These adverse reactions were mild and self limiting. It is concluded that
      inosine pranobex demonstrated a significant pharmacological activity in
      subclinical HPV infection of the vulva and should be considered an alternative
      treatment for the condition.

PMID- 8876360
TI  - Men with repeated episodes of gonorrhoea 1990-1992.
AB  - Patients who acquire repeated infections of gonorrhoea are well described. A
      study was undertaken of male patients attending a central London clinic in an
      attempt to identify features of those acquiring repeated infections to facilitate
      risk reduction strategies. During the 3 years 1990 to 1992, 18.8% of patients
      contributed 35.8% of episodes with a mean time between episodes of 10.5 weeks.
      Those with repeat infections were more likely to be black and to have had more
      than one episode of gonorrhoea prior to the study period. They are also more
      likely to have had 3 or more recent partners. While those with repeated
      infections do not form a homogeneous group there are certain characteristics that
      should enable targeting of a subgroup.

PMID- 8876361
TI  - Recurrent bacterial vaginosis--an old approach to a new problem.
AB  - Bacterial vaginosis (BV) is a common cause of abnormal malodorous vaginal
      discharge and can be frustrating to manage in its recurrent form. Metronidazole
      is the standard treatment, but is unacceptable to many women when given
      repeatedly. Results of treating recurrent BV using a single vaginal washout with
      3% hydrogen peroxide are analysed. A total of 30 symptomatic women with
      clinically confirmed recurrent BV in the absence of other genital infections were
      recruited after informed consent. Hydrogen peroxide (3%) was instilled into the
      vagina, left for 3 minutes and drained. Reassessment was at 3 weeks after
      treatment. A total of 23 women completed the study. Symptoms cleared completely
      in 78% (18/23), improved in 13% (3/23) and remained unchanged in 9% (2/23). All
      the 3 women with improved symptoms had a mild vaginal discharge, but only one of
      them was still able to perceive the malodour. The amine test was negative in all
      23 women including the 2 (9%) who felt no change in their symptoms following
      treatment. Mixed anaerobes isolated in all women before treatment were not re
      isolated, and microscopy did not show 'clue cells' in the vaginal discharge
      following treatment. Vaginal acidity was restored to normal in all but one (96%).
      No side-effects were observed in the treated women. Hydrogen peroxide (3%) used
      as a single vaginal wash was as effective as any other agent in current use in
      clearing the vaginal malodour of bacterial vaginosis at 3 weeks after treatment.

PMID- 8876363
TI  - Penile implant as a risk factor for sexually acquired gonococcal and chlamydial
      urethritis in the elderly.

PMID- 8876362
TI  - Determination of T-lymphocyte subsets on site in rural Tanzania: results in HIV-1
      infected and non-infected individuals.
AB  - With the FACSCount flow cytometer, counts of CD4, CD8 and CD3 lymphocytes and
      CD4/CD8 ratios were performed in a rural hospital in Tanzania. A total of 168
      subjects (21 HIV-1 seropositive and 147 HIV-1 seronegative) were tested as part
      of a population-based serosurvey and AIDS education programme; 134 other subjects
      were hospitalized patients who had signs and symptoms suggestive of AIDS (69 HIV
      1 seropositive and 65 HIV-seronegative). Mean values for the 147 HIV-1
      seronegative subjects from the local population were 980 CD4 cells (95% CI 930,
      1031), 598 CD8 cells (560, 635) and CD4/CD8 ratio 1.78 (1.68, 1.89). Seropositive
      subjects from the local population had significantly lower CD4 cell counts,
      higher CD8 counts and a lower CD4/CD8 ratio. CD4 cells were significantly lower
      and CD8 cells significantly higher in HIV-1 seropositive hospital patients
      compared to HIV-1 seronegative patients. However, 23 (35%) seronegative hospital
      patients had CD4 counts lower than 600. These results establish baseline values
      for the lymphocyte subsets in this population and indicate that this technique
      can be used in remote areas to monitor progress of HIV-infected individuals.

PMID- 8876364
TI  - Systemic strongyloidiasis complicating HIV: a promising response to ivermectin.

PMID- 8876365
TI  - Arsenical pessaries in the successful elimination of metronidazole-resistant
      Trichomonas vaginalis.

PMID- 8876366
TI  - National standards for the management of gonorrhoea.

PMID- 8876367
TI  - National standards for contact tracing in gonorrhoea. Royal College of
      Physicians, National Audit Development Programme in Sexual Health.

PMID- 8876368
TI  - Atovaquone as prophylaxis for Pneumocystis carinii.

PMID- 8876369
TI  - The importance of transmission of HIV-1 in discordant couples in the population
      dynamics of HIV-1 infection in rural Africa.

PMID- 8876370
TI  - Sex, lies, and genitourinary medicine.

PMID- 8876371
TI  - Clinical aspects of erectile dysfunction.

PMID- 8876372
TI  - Autonomic nervous system disorders and erectile dysfunction.

PMID- 8876373
TI  - Psychological management of erectile dysfunction and related disorders.

PMID- 8876374
TI  - Intrapenile drug delivery systems.

PMID- 8876375
TI  - Oral treatments for erectile dysfunction.

PMID- 8876376
TI  - Surgical management of erectile dysfunction.

PMID- 8876377
TI  - Financial implications of an erectile dysfunction clinic in a Trust hospital.

PMID- 8876378
TI  - The treatment of patients with diabetes.

PMID- 8876379
TI  - Cloning and high expression of rabbit FKBP25 in cornea.
AB  - Rabbit 25 kDa FK-506/rapamycin binding protein (FKBP25) cDNA was isolated during
      a screening of rabbit corneal endothelial cDNA library. The cDNA clone was a 955
      bp fragment with a 670 bp open reading frame and a 285 bp 3' non-coding region.
      The cDNA and deduced amino acid sequences were 91.7 and 96.4% identical,
      respectively, to previously reported human FKBP25B sequences. The lysine-rich
      region KK(X)7KK(X)26KKKK, which plays an important role in nuclear translocation
      in rabbit FKBP25, was recognized. Reverse transcription-polymerase chain reaction
      (RT-PCR) amplification of rabbit FKBP25 and FKBP12 in selected rabbit organs,
      including total cornea, showed higher expressions in cornea, retina, cerebrum and
      cerebellum than other compared tissues. RT-PCR amplification in rabbit cultured
      corneal cells showed expressions in all cultured corneal epithelial, stromal,
      endothelial, and especially in SV40-adenovirus vector-immortalized epithelial
      cells. The higher expressions of FKBP25 and FKBP12 suggest significant roles for
      FKBPs in those tissues.

PMID- 8876380
TI  - Membrane-bound carbonic anhydrase activity in the rat corneal endothelium and
      retina.
AB  - Localization of carbonic anhydrase (CA) was investigated in the rat eye by light
      and electron microscopy, and the inhibitory effects on CA distribution in the rat
      eye were compared between dorzolamide and acetazolamide. The cobalt sulfide
      histochemical method was used to study the CA localization. Acidic osmification
      was carried out for postfixation of the electron microscopic observations. The
      inhibition of CA activity was examined with different concentrations of
      acetazolamide and dorzolamide. The cytoplasm, lateral cell membranes and
      karyoplasm of the corneal endothelium showed CA activity. In the retina, the
      processes and cell bodies of Muller cells, the tips of the outer segments of the
      rods, and apical villi and basolateral membranes of the pigment epithelium
      indicated CA activity. CA activity was inhibited by dorzolamide at lower
      concentrations than needed for acetazolamide and only the CA activity of the
      nerve fiber layer remained at 10(-6) M of acetazolamide and 5 x 10(-7) M of
      dorzolamide. The presence of membrane-bound CA activity was confirmed in the
      corneal endothelium and Muller cells. CA activity was also demonstrated in the
      apices of rod outer segments and scleral fibroblasts. The CA inhibition test
      revealed that dorzolamide was a stronger CA inhibitor than acetazolamide and that
      the CA activity of the nerve fiber layer was strongest in the rat eye.

PMID- 8876381
TI  - Excimer laser corneal surgery and free oxygen radicals.
AB  - Corneal photoablation with 193 nm argon fluoride excimer laser is a new technique
      for the treatment of refractive errors and for removing corneal opacities and
      irregularities. Ultraviolet radiation and thermal injury induce free radical
      formation in the tissues. The aim of this study was to confirm the production of
      free radicals by excimer laser photoablation in rabbits. The thermal changes of
      the posterior corneal surface were recorded during excimer laser photoablation.
      The lipid peroxide (LPO) levels and superoxide dismutase (SOD) activities of
      aqueous humour were measured after excimer laser keratectomy. The aqueous LPO
      levels were not changed after excimer laser ablation, but both the thermal
      increase in the cornea during the photoablation and the decreased aqueous SOD
      activities suggest that free radicals are formed in the cornea during excimer
      laser keratectomy, and that they may be responsible for some of the complications
      of excimer laser corneal surgery.

PMID- 8876382
TI  - Possible roles of AMPA/KA receptor in cultured Muller cells.
AB  - In order to identify the function of the AMPA/KA (alpha-amino-3-hydroxy-5-methyl
      4-isoxazole propionate/kainate) receptor in cultured Muller cells, we studied the
      difference in the affinity of this receptor for cultured Muller cells and retinal
      neurons (neurons), comparing these to the characteristics of cultured Muller
      cells exposed to kainate (KA), a neurotoxic amino acid. The difference in the
      cellular responses of Muller cells and neurons to AMPA was evaluated by measuring
      the rapid change in intracellular calcium ions. Results showed that neurons were
      more sensitive to AMPA than Muller cells; the percentage of cells responding to
      AMPA was always higher for neurons. When Muller cells were exposed to 0.5 mM KA,
      the morphology of the cells was not affected and the concentration of lactate
      dehydrogenase in the culture solution did not increase. However, the percentage
      of cells responding to a high concentration of AMPA was higher in the Muller
      cells exposed to KA than in those not exposed. These findings indicated that the
      affinity of the AMPA receptor was lower in Muller cells than in neurons, and that
      Muller cells were resistant to neurotoxic amino acids. It was also suggested that
      when an extremely large amount of neurotoxic amino acid was released into the
      retina as a result of ischemia, Muller cells actively protected the neurons.

PMID- 8876383
TI  - Topical SDZ GLC-756, a novel dopamine D-1 antagonist and D-2 agonist, lowers
      intraocular pressure in conscious rabbits.
AB  - This investigation was carried out to evaluate the effect of SDZ GLC-756, a novel
      dopamine D-1 antagonist and D-2 agonist, on intraocular pressure (IOP) in
      rabbits. A randomized, placebo-controlled, double-masked, crossover study with
      topical application of SDZ GLC-756 eyedrops [0.015% (n = 10), 0.03% (n = 10),
      0.0625% (n = 10), 0.125% (n = 9), 0.25% (n = 10), 0.5% (n = 14)] and vehicle
      alone (placebo-control) to the right eye was performed in New Zealand White
      rabbits. The contralateral eye received no treatment. IOP was measured using a
      pneumatonometer. Topical SDZ GLC-756 significantly lowered IOP in a dose
      dependent manner (maximal IOP-lowering effect 1 approximately 2 hours after
      administration) in the treated eye and, to a lesser extent, in the contralateral
      eye. The duration of action was approximately 4 hours. The simultaneous D-1
      antagonistic and D-2 agonistic properties of SDZ GLC-756 may provide a new
      pharmacological approach to the treatment of glaucoma, which deserves further
      investigation.

PMID- 8876384
TI  - Role of ICAM-1 and LFA-1 in endotoxin-induced uveitis in mice.
AB  - The effect of monoclonal antibodies against adhesion molecules on the development
      of endotoxin-induced uveitis (EIU) and interleukin-1 (IL-1)-enhanced EIU were
      studied. When endotoxin or IL-1 was injected into C3H/HeN mice, the expression of
      intercellular adhesion molecule-1 (ICAM-1) on the ciliary body was up-regulated
      as determined by immunohistochemical assay. However, these agents did not alter
      lymphocyte function-associated antigen-1 (LFA-1) expression on leukocytes when
      whole blood cells were analyzed with flow cytometry. Monoclonal anti-ICAM-1
      antibody or anti-LFA-1 antibody was intraperitoneally administered to C3H/HeN
      mice simultaneously with endotoxin, and the effect on the development of EIU was
      studied. The cell number in aqueous humor and frequency of posterior synechiae
      were markedly decreased in EIU when either antibody was administered. However,
      protein concentration in the aqueous humor was not statistically reduced by the
      injection of these antibodies. In the model of IL-1 enhanced EIU, not only the
      cell number and frequency of posterior synechiae but also protein concentration
      were decreased. Moreover, there were no differences between these two antibodies
      in the effect on EIU, whereas anti-LFA-1 antibody was more effective than anti
      ICAM-1 antibody in IL-1-enhanced EIU.

PMID- 8876385
TI  - Membranous nature of premacular vitreous cortex in the human eye.
AB  - To characterize the morphologic nature of the premacular vitreous, we examined
      the posterior vitreous of 24 normal autopsy eyes without posterior vitreous
      detachment (PVD) by biomicroscopy and scanning electron microscopy (SEM). For
      biomicroscopic observation, the vitreous was stained with fluorescein and
      immersed in water. The posterior portion of the eyeball was then desiccated and
      examined by SEM. The vitreous cortex was extremely thin in the premacular area,
      and premacular liquefied lacuna was invariably seen in front of the thin vitreous
      cortex by biomicroscopic observations. In SEM the premacular vitreous cortex
      appeared to be a cellophane-like membrane overlying the retina at x40
      approximately 100 magnification. A meshwork structure could be seen in the
      cellophane-like membrane at the magnification of approximately x1000. The
      diameter of fibers in the meshwork was compatible with that of vitreous collagen.
      We confirmed that the premacular vitreous cortex was of a membranous nature
      distinct from the vitreous gel in eyes without PVD.

PMID- 8876386
TI  - Immunohistochemical localization of cytosolic sialidase in photoreceptor cells.
AB  - The binding sites of the antibody to cytosolic sialidase on the rat and monkey
      photoreceptor cells were examined immunohistochemically using the avidin
      biotinylated peroxidase method. In the rat photoreceptor cells, the antibody
      bound diffusely to the inner segment and the outer nuclear layers which are
      composed chiefly of rod cells. In the monkey photoreceptor cells, the antibody
      bound to the rod inner segments which were clearly distinct, morphologically,
      from the cone inner segments. The antibody also bound to the rod cell bodies in
      the outer nuclear layer. These binding patterns show that the antibody bound
      preferentially to rod photoreceptor cells. This observation is consistent with
      previous lectin histochemical findings that sialoglycans are preferentially
      present on the surfaces of rod photoreceptors, and in the rod-associated
      interphotoreceptor matrix. Sialidase in rod inner segments may function by
      balancing with sialyltransferase, also preferentially expressed in rod inner
      segments, to form sialyl residues on the termini of sugar chains in the rod
      associated sialoglycoconjugates.

PMID- 8876387
TI  - Immunohistochemical proof of origin of macrophages in laser photocoagulation
      lesion in the retina.
AB  - The origin of the macrophages which appear in the subretinal space after laser
      photocoagulation on the rat retina was investigated using immunohistochemistry.
      The majority of macrophages located in laser lesions were found to be positive to
      staining for the specific rat monocyte/macrophage marker (ED1). The number of
      macrophages and activated macrophages were abundant after intense laser
      photocoagulation in which choroidal neovascularization was induced. After the
      retinal pigment epithelium (RPE) was damaged by intravenous administration of
      sodium iodate, the number of migrating macrophages in the subretinal space of
      lasered areas significantly decreased to a level comparable to the level found in
      control animals. These results suggested that the macrophages were derived mainly
      from monocytes in the blood, not from RPE cells, and that they may play a role in
      the development of the choroidal neovascularization.

PMID- 8876388
TI  - Time-course of changes in nicardipine effects on microcirculation in retina and
      optic nerve head in living rabbit eyes.
AB  - The effects of intravenous administration of a calcium antagonist, nicardipine,
      on microcirculation in the retina and optic nerve head (ONH) of rabbit eyes were
      investigated using a laser speckle microcirculation analyzer. The rabbit fundus
      was illuminated by an argon (blue) laser spot to measure the retina or by a diode
      laser spot to measure the ONH, and the image speckle was detected by an image
      sensor. The difference between the average of the speckle intensity (Imean) and
      the speckle intensity for successive scannings was calculated, and the ratio of
      Imean to this difference was defined as normalized blur (NB); a quantitative
      index of blood velocity in tissue. The average NB over the field measured (0.62 x
      0.62 mm in the retina and 0.42 x 0.42 mm in the ONH) was calculated to give NBav,
      which was found to show a significant correlation with the retinal blood flow
      rate determined using a microsphere technique. In Dutch rabbits for measurement
      in the retina and in albino rabbits for measurement in the ONH (nicardipine
      group), 0.4 mL/kg of 0.01% nicardipine hydrochloride dissolved in physiological
      saline was injected intravenously into anesthetized animals. To serve as control,
      other groups of Dutch or albino rabbits were injected with 0.4 mL/kg of
      physiological saline. Mean femoral arterial blood pressure (FABPm) in the
      nicardipine group dropped to the minimum at 1 minute post-injection and this
      level remained significantly lower than that in the control group up to 15
      minutes post-injection. The pulse rate, pH, Pco2 and Po2 of arterial blood, body
      temperature and the intraocular pressure did not show any significant changes
      during the experiment. The NBav obtained from the retina in the nicardipine group
      showed a significant transient decrease, probably due to the initial drop in the
      FABPm, followed by a significant increase after the FABPm returned to the
      baseline. The time-course of NBav obtained from the ONH in the nicardipine group
      showed little change. These results suggest that nicardipine may have
      considerable potential in the treatment of ocular diseases associated with
      insufficient retinal blood flow. The nicardipine effects observed here deserve to
      be studied further in human eyes.

PMID- 8876389
TI  - The effectiveness of two ciprofloxacin formulations for experimental Pseudomonas
      and Staphylococcus keratitis.
AB  - Ciprofloxacin is a fluoroquinolone antibiotic with broad spectrum bactericidal
      activity. A commercially available form of ciprofloxacin contains benzalkonium
      chloride (BAC) (0.006%) and EDTA (0.05%) as preservatives. Since BAC has been
      shown to cause adverse changes in corneal epithelial cells, a formulation of
      ciprofloxacin devoid of BAC and EDTA but with the same effectiveness would be
      valuable. We present here the results of experiments designed to assess the
      efficacy of a BAC-free and EDTA-free formulation of ciprofloxacin, Ciprofloxacin
      polystyrene sulfonate (PSS), in experimental models of Pseudomonas aeruginosa and
      Staphylococcus aureus keratitis. Both formulations of ciprofloxacin sterilized
      corneas infected with P aeruginosa, and both formulations showed equal
      bactericidal activity for S aureus. Normal eyes treated with either formulation
      showed mild conjunctival irritation compared to untreated normal eyes. The
      bactericidal activities of both formulations of ciprofloxacin were excellent.
      Therefore, the Ciprofloxacin-PSS formulation could serve as an effective single
      drug therapy for ocular infections.

PMID- 8876390
TI  - Effects of local hypothermia on ischemic eyes in vitrectomy.
AB  - The effects of local hypothermia on postoperative inflammation, electroretinogram
      (ERG) and histological changes of the retina were evaluated in experimental
      vitrectomy in pressure-induced ischemic rabbit eyes. The solutions used for
      intraocular perfusion were maintained at 8 degrees C, 22 degrees C or 38 degrees
      C. Following closed vitrectomy, the vitreous cavities of the rabbit eyes were
      irrigated for 30 minutes with the perfusion pressure set at 70 mmHg. The blood
      flow in the posterior area of the eye was reduced to about one-sixth of the
      preoperative level during ischemia. Aqueous protein concentrations showed no
      significant diversities among the different temperature groups on postoperative
      days 1 and 7. Recovery of ERG was investigated after a given time of ischemia.
      There were no significant differences in the recovery of either a-wave or b-wave
      amplitudes among the different temperature groups; although the average b-wave
      amplitude in the 38 degrees C group alone failed to return to the preoperative
      level on the 7th postoperative day. Light microscopy showed an irregular
      distribution of retinal damage in all groups. The damaged regions showed
      significantly greater histologic impairment in the 38 degrees C group than in
      either the 8 degrees C or 22 degrees C group. The results of our experiments
      suggest that local hypothermia during vitrectomy in ischemic eyes decreases
      retinal damage and, therefore, it seems inadvisable to use intraocular solutions
      warmed to body temperature.

PMID- 8876392
TI  - Long-term results of surgery for superior oblique palsy.
AB  - The results one month after surgery in 159 cases of superior oblique palsy were
      compared according to the method of surgery with the results 4 years or longer
      after surgery. There were 141 cases of congenital palsy and 18 cases of acquired
      palsy, for a total of 159 cases. Our study showed that surgery on the oblique
      muscle provided long-lasting effects, while recession of the superior rectus
      muscle or recession of the contralateral inferior rectus muscle could cause late
      overcorrection. When performing surgery on the rectus muscle, careful attention
      must be paid to suturing the muscle.

PMID- 8876391
TI  - Results of surgery for paralytic esotropia due to abducens palsy.
AB  - The surgical effects of three methods, transposition of the vertical rectus
      muscles, Jensen's procedure, and resection (advancement) of the lateral rectus
      muscle, were compared among 109 cases of paralytic esotropia due to abducens
      palsy. These procedures were combined with recession of the medial rectus muscle
      in about half the cases. Of the 109 cases, 22 were followed up for 4 years or
      longer. Results were similar, provided that the following protocols for surgery
      were adhered to: in cases of complete paralysis, transposition of the vertical
      rectus muscles was done, and in cases of incomplete paralysis, resection
      (advancement) of the lateral rectus muscle was performed. With both procedures,
      results were improved if recession of the medial rectus muscle was carried out at
      the same time.

PMID- 8876393
TI  - Evaluation of pupillary block component in angle-closure glaucoma.
AB  - To evaluate the amount of the pupillary block component in primary angle-closure
      glaucoma, the dark-room prone-position test was carried out in 30 eyes of 20
      primary angle-closure glaucoma patients, before and one month after argon laser
      iridotomy. The pupillary block component in the prone position (5.8 +/- 5.6
      mmHg), which is the amount of reduction in IOP rise in the post-laser dark-room
      prone-position test, composed 67.8% of the IOP rise in the pre-laser dark-room
      prone-position test (8.6 +/- 5.6 mmHg). The amount of the pupillary block
      component correlated significantly with the IOP rise in the pre-laser dark-room
      prone-position test (r = 0.880, P < 0.001). The amount of the non-pupillary block
      component was relatively constant and correlated poorly with the IOP rise in the
      pre-laser dark-room prone-position test (r = 0.163, P = 0.386). The pupillary
      block component was significantly larger than the non-pupillary block component
      in the eyes with an IOP rise of > or = 7 mmHg in the pre-laser dark-room prone
      position test (P < 0.01). The dark-room prone-position test could be useful in
      evaluating the pupillary block component in angle-closure glaucoma eyes and
      helpful in making a decision for laser iridotomy.

PMID- 8876394
TI  - Non-rubeotic angle-closure glaucoma associated with ciliary medulloepithelioma.
AB  - Non-rubeotic angle-closure glaucoma associated with ciliary medulloepithelioma
      was reported in a 3-year-old boy. On the first visit, a free-floating white mass
      was observed in the anterior chamber of his right eye. The mass disappeared
      spontaneously after 5 months of observation. One year later, angle-closure
      glaucoma with peripheral anterior synechia occurred in the same eye and
      intraocular pressure rose to 55 mmHg. After glaucoma surgery, the white mass
      appeared again in the anterior chamber of his right eye. By cycloscopy, numerous
      small grayish-white masses could be seen on the ciliary body and in the posterior
      chamber. Histopathological examination of one mass confirmed medulloepithelioma
      and the eye was enucleated. Disseminated tumor cells in the anterior chamber had
      caused the cornea and the peripheral iris to adhere to each other, resulting in
      the formation of peripheral anterior synechia.

PMID- 8876395
TI  - Lectin-histochemical study of O-linked glycoconjugates in dysplastic retina of
      Norrie disease.
AB  - The carbohydrate chains of O-linked glycoconjugates in dysplastic retina from a
      Japanese female infant with Norrie disease were examined by lectin
      histochemistry. The avidin-biotinylated peroxidase method was used. The retina
      was highly dysplastic and composed of undifferentiated embryonic tissues
      containing a number of rosettes of varying sizes. The lumina of the rosettes were
      stained by peanut agglutinin, which recognizes the Gal beta 1,3GalNAc sequence of
      O-linked glycans. However, the lumina were not labeled by wheat germ agglutinin,
      which reacts with sialic acid and/or N-acetylglucosamine. These observations
      suggest that the O-linked glycoconjugates in the lumina of rosettes were not
      sialylated in the present case. Their lack of terminal sialic acids may be
      related to the rosette formation.

PMID- 8876396
TI  - Familial occurrence of Behcet's disease.
AB  - The familial occurrence of Behcet's disease in the 564 Behcet's patients treated
      in the Uveitis Survey Clinic of the Hokkaido University Hospital between 1967 and
      1992 was investigated. Familial occurrence of Behcet's disease was found in 18
      patients from 9 families. The male-to-female ratio was 3.5 in the familial cases,
      which was significantly higher than in the sporadic cases. Familial occurrence
      was most frequently seen among siblings. Most patients, including all female
      patients, had the complete type. They had typical ocular lesions, and exhibited
      bilateral uveoretinitis with poor visual prognosis, particularly the female
      patients. Frequency of HLA-B5 was 92% in the familial patients, which was much
      higher than in both the controls and the sporadic cases. It seems probable that
      patients with familial occurrence of this disease have a poorer prognosis with
      more susceptible immunogenetic backgrounds.

PMID- 8876397
TI  - Ocular manifestations in patients with HTLV-I associated infection--a clinical
      study of 93 cases.
AB  - The purpose of this study was to confirm that ophthalmological features seen in
      patients in Martinique, French West Indies, could be linked to infection by HTLV
      I. The authors studied 93 HTLV-I infected patients divided into 70 patients with
      HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 23
      asymptomatic HTLV-I carriers. They did a complete ophthalmological examination
      with an assessment of lacrymal secretion by means of three tests: Shirmer 1,
      break-up time and rose Bengal. Some patients had a biopsy of secondary salivary
      glands. When possible, detection of HTLV-I antibodies was carried out in the
      aqueous humor. In 45 of the 93 patients (48.4%) the presence of dry
      keratoconjunctivitis was recorded. In 22 of these 45 cases, a biopsy of the
      secondary salivary glands showed the presence of lymphoplasmocytoid infiltrations
      comparable to the glandular changes that occur with Gougerot-Sjogren syndrome.
      Among the 93 patients, 15 cases of uveitis were noted (16.1%) with 13 cases of
      anterior uveitis and 11 cases of vitritis. The inflammation was bilateral in 9
      cases (9/15 = 60%). Two cases of cotton wool spots, 3 cases of abnormalities in
      the distribution of the retinal pigment and 7 cases of corneal lesions were also
      noted. Higher levels of anti-HTLV-I antibodies were detected in the aqueous humor
      of 3 patients with uveitis. The coexistence of dry eye (keratoconjunctivitis),
      uveitis and retinal microangiopathy in patients who are suffering from HAM/TSP
      could suggest the involvement of an autoimmune or immunological mechanism in the
      physiopathology of the illness.

PMID- 8876398
TI  - Corneal endothelial cell proliferation and migration after penetrating
      keratoplasty in rabbits.
AB  - The proliferation of the host endothelial cells during healing after penetrating
      keratoplasty (PKP) was investigated by exchange PKP in two groups of adult
      rabbits. After the endothelia of group A rabbits were selectively damaged by
      intracameral injection of benzalkonium chloride (BAK), grafts were made and
      transplanted to group B, untreated normal rabbits (damaged graft group). Grafts
      from group B rabbit eyes had already been made and these subsequently were
      transplanted to group A rabbits (normal graft group). Corneas were excised 4, 7,
      14 and 28 days postoperatively, labeled with 3H-thymidine and subjected to
      autoradiography. The results indicated that in corneas with grafts damaged with
      BAK (damaged graft group), normal host endothelial cells proliferated and
      migrated into the damaged graft 4 days after surgery. In the normal graft group,
      the endothelial cells of the graft did not migrate to the damaged host cornea. On
      day 28, a monolayered apparently normal endothelium was regenerated in the
      damaged graft group. These results suggest that the proliferation of host corneal
      endothelial cells is vital in the endothelial healing of the graft after PKP in
      rabbits.

PMID- 8876400
TI  - Addiction nursing and substance misuse: a slow response to partial accommodation.

PMID- 8876399
TI  - Serotyping of Chlamydia trachomatis from inclusion conjunctivitis by polymerase
      chain reaction and restriction fragment length polymorphism analysis.
AB  - A molecular biological method of detecting and serotyping Chlamydia trachomatis
      (C. trachomatis) directly from conjunctival specimens by polymerase chain
      reaction (PCR) was developed and applied to the diagnosis of inclusion
      conjunctivitis. We amplified 1.2 kbp DNA fragments of ompA gene from 15 reference
      strains of C. trachomatis by two-step PCR using two pairs of primers. Restriction
      fragment length polymorphism analysis using a combination of three endonucleases
      (HinfI, HindIII and HhaI) completely differentiated 13 of the 15 serovars; the
      exceptions were B and Ba. We then used this method for 18 strains of C.
      trachomatis isolated from Japanese patients with inclusion conjunctivitis,
      serotyping them into six groups: D (5/18), G (5/18), E (3/18), H (2/18), F
      (1/18), and K (1/18). In our comparison of cell culture isolation with PCR
      analysis of 38 conjunctival swabs from 35 patients in Sapporo with follicular
      conjunctivitis, 8 were positive in culture isolation and were also positive in
      two-step PCR. Twenty-five of 26 strains (the 18 isolated strains and 8 strains
      amplified by two-step PCR) were genotyped to D, G, H, E, F, and K. One isolated
      strain could not be identified. The C. trachomatis which causes inclusion
      conjunctivitis in Japan appears to have a distribution of serovars similar to
      that of the sexually transmitted diseases.

PMID- 8876401
TI  - Maternal thinking in dementia care.
AB  - Carers of demented people living in a group dwelling were interviewed and
      observed individually and together. The aim of the study was to illuminate the
      thinking of pre-identified good dementia carers and to make explicit their means
      of understanding demented people. The tape-recorded and transcribed interviews
      were interpreted using a phenomenological hermeneutic method. The findings showed
      that these carers explicitly referred to the concept of mother, used when
      explaining their ability to understand demented people. They created a home-like
      atmosphere together with the inhabitants. The findings were interpreted
      metaphorically as maternal love, thinking and practice in creating an
      understanding relationship with the demented people they cared for. This
      metaphorical aptitude considered the fulfilment of life for these demented people
      and included partly unconscious tools that the carers used to compensate for the
      loss of abilities suffered by the demented people. The carers' attitudes towards
      the inhabitants of the ward and each other were based on respect as in a
      functioning family. Their ambition was interpreted as an attempt to create an
      atmosphere that functioned not only as an institution, but as an incubator for
      human lives, which had become dependent on others for their survival and the
      preservation of their human dignity throughout their physical existence.

PMID- 8876402
TI  - Effects of an environmental manipulation emphasizing client-centred care on
      agitation and sleep in dementia sufferers in a nursing home.
AB  - This study was designed to determine whether a change from a task-oriented care
      approach to a client-oriented care approach affects (a) the level of agitation
      and (b) 24-hour sleep in residents suffering from dementia in a nursing home. The
      levels of dementia and sleep of 33 nursing home residents were measured four
      times over 12 weeks (twice before and twice after the change in care approach)
      using the Cohen-Mansfield agitation inventory and the dementia mood assessment
      scale. Verbal agitation levels significantly decreased 6 to 8 weeks following the
      change, whereas more infrequent agitated behaviours, which were classified as
      'other', significantly increased. Daytime sleep increased initially after the
      change but then returned to baseline levels after 6 weeks. While the main focus
      of the study was on residents' behaviour following an environmental manipulation,
      anecdotal observations of staff members interactions with residents indicated
      that they felt less rushed and were more tolerant of residents' behaviour
      following the intervention.

PMID- 8876403
TI  - Nursing attitudes to the care of elderly patients at risk of continuing hospital
      care.
AB  - This study assesses changes in nurses' attitudes to the process of decision
      making regarding the care of elderly patients identified as being at risk of
      continuing (long-term) hospital care. It was undertaken during the course of an
      evaluation of an intervention programme which involved a new approach to decision
      making concerning the long-term care of dependent elderly patients. Complementary
      components of the intervention programme were: (a) an early discharge planning
      service; and (b) an extended home care programme. The programme involved close
      liaison of specially trained community health nurses with staff members of the
      general medical wards of a large general hospital. At the onset of the
      evaluation, it was perceived by management that the staff of the general medical
      wards favoured continuing hospital care for very dependent elderly patients
      rather than community care. It was hypothesized that the intervention programme
      would result in a change in ward staffs' attitudes concerning the feasibility of
      home-based care and how decisions about care should be made. To test this,
      attitude changes of community health nurses and ward nurses were assessed over
      the period of implementation of the programme. Following the introduction of the
      programme, the study found that some of the ward nurses' attitudes became closer
      to those of community health nurses. There was a shift in ward nurses' attitudes
      away from a professional approach to decisions about the care and placement of
      very dependent elderly patients to a 'patient choice' approach. Nurses felt more
      strongly that they had an important role in patient care. Implications of the
      research are considered in relation to the process of discharge planning.

PMID- 8876404
TI  - Functional status of the oldest-old in a home setting.
AB  - The purpose of this cross-sectional study was to examine six domains of
      functioning: physical, mental, social, spiritual, economic and activities of
      daily living. The primary inclusion criteria at the time of recruitment were that
      participants be over the age of 85, be cognitively intact, and be living in a
      home setting. Instruments used for the study included the Older Americans
      Resource Survey (OARS), Mini-Mental Status Examination (MMSE), Geriatric
      Depression Scale (GDS), Spiritual Well Being Scale (SWBS). Fifty subjects, mean
      age 89 years, lived alone (65%) or with their spouse (22%) in their homes.
      Person's correlation analysis found significant relationships among physical,
      mental, social, economic and activities of daily living. Good to excellent
      functioning was found in the mental (82%) and social (82%) domains. Highest
      functional impairments were identified with ability to carry out activities of
      daily living (72%) and in the domains of physical functioning (55%). Common
      chronic illnesses reported were arthritis (56%), hypertension (46%) and cardiac
      problems (30%). The average daily use of prescribed drugs was three times and
      over-the-counter use was once per day. Eleven per cent of subjects were mildly
      (7%) or moderately (4%) depressed. Subjects reported that they needed visiting
      nurses (29%), home health aids (20%) and help with shopping (24%) and
      transportation (24%). The data suggest that multidimensional assessment is
      necessary to identify nursing interventions that will regain, maintain or enhance
      functioning among oldest-old people.

PMID- 8876405
TI  - Health within illness: experiences of chronically ill/disabled people.
AB  - The concept of health within illness is beginning to gain recognition in nursing.
      However, there has been little research to explore and describe this phenomenon.
      The results of a recent study investigating the meaning of the experience of
      feeling healthy for people living with a chronic illness and/or disability are
      presented. An interpretive phenomenological study was undertaken with eight
      participants living with a variety of different chronic conditions. The results
      provide a rich mosaic of themes describing the participants' health experiences.
      These themes include: (a) honouring the self; (b) seeking and connecting with
      others; (c) creating opportunities; (d) celebrating life; (e) transcending the
      self; and (f) acquiring a state of grace. The significance of these results is
      that they provide for a reconceptualization of health and illness. Such a
      reconceptualization calls for a transformation in nursing care, from a problem
      focus and a deficit perspective, to one which focuses on the client's capacity
      and the promotion of health and healing.

PMID- 8876406
TI  - Expressed emotion on long-stay wards.
AB  - We examined the influence of an educational programme on nurses' level of
      expressed emotion (EE), on ward climate and on social functioning and
      psychopathology of hospitalized schizophrenic patients. Nurses and patients were
      from long-stay wards of six Dutch psychiatric hospitals. Despite an increase of
      nurses' knowledge about schizophrenia we did not find measurable effects on
      nurses' levels of EE. According to the five minute speech sample method, a third
      of the nurses participating in this study had a high level of expressed emotion,
      mainly consisting of criticism. This was a rather stable pattern. Patients,
      however, were reluctant to give their nurses high EE ratings on the level of
      expressed emotion scale. Psychopathology was not influenced by the educational
      programme, but social functioning of patients was related to EE in nurses.
      Moreover, we found a significant decline in the number of restrictive ward rules
      at follow-up. We conclude that, while it may be difficult to detect changes in EE
      level after an educational programme for nurses, there nevertheless appear to be
      measurable benefits for patients.

PMID- 8876407
TI  - General satisfaction and satisfaction with nursing communication on an adult
      psychiatric ward.
AB  - A client satisfaction survey was undertaken on an adult psychiatric admission
      ward in Sheffield, England, being sent to all clients discharged from the ward
      over 12 months. The questionnaire consisted of a general satisfaction element,
      and two questions asking about satisfaction with nursing communication. The
      response rate was 81 from 199 forms sent. General satisfaction levels were lower
      than for a sample of 3120 mainly out-patient psychiatric clients in the USA.
      Satisfaction with nursing communication was significantly correlated with general
      satisfaction. The survey allowed the number of dissatisfied clients to be
      identified, and their views highlighted. One aspect often reported by
      dissatisfied clients was a perceived lack of time from staff. The importance of
      nursing communication with respect to client satisfaction is highlighted by the
      study.

PMID- 8876408
TI  - Establishing good practices in continuing care: a descriptive study of community
      nursing services for people with HIV infection.
AB  - This paper presents findings from a 2-year study of community nursing services
      for people affected by HIV infection in six health authorities in England. The
      research, commissioned by the Department of Health, England, aimed to identify
      the main bridges and barriers to effective home nursing care, focusing on
      discharge co-ordination, district nursing and multi-agency collaboration. Using a
      triangulated, case study approach, the main methods of data collection included
      non-participant observation, case note analysis, semi-structured staff
      interviews, a postal questionnaire of district nurses and a series of focus
      groups with service users. Study sites included three cities and surrounding
      districts in the north west, north and south east of England. Findings suggest
      there is considerable room for improvement in discharge planning and that good
      practice is not the preserve of specialist units. District nurses are shown to be
      willing providers of the majority of home nursing care to this client group, but
      there is a need for more focused training, greater use of care co-ordinators and
      more emotional and managerial support.

PMID- 8876410
TI  - The family interview: exploring experiences of family health and well-being.
AB  - Health and well-being are basic concepts to nursing science and also important to
      practical nursing care: to provide effective nursing we need to have a good
      understanding of both health and well-being. Experienced health has been studied
      quite extensively at the individual level, but the family's point of view has
      been very much neglected. This study collected data on families' views on health
      and well-being in interviews with nine families. The interviews were held in a
      group situation, with all family members present, and they were structured around
      the three core themes identified by Astedt-Kurki in her doctoral dissertation:
      'doing, knowing, feeling'. The emotional bonds that tie together family members
      may be a factor in the family's tendency to produce rich and detailed knowledge
      about their well-being in interview situations. On the other hand it is also
      possible that the family will try to convey as positive an image of itself as
      possible. For reasons of reliability the nine families taking part in this study
      were interviewed twice.

PMID- 8876409
TI  - Negotiating the role of the practice nurse in general practice.
AB  - The debate about the role of the practice nurse is not only about practice
      nursing per se, but raises broader issues about the organization of primary
      health care. Two related issues emerge as significant: the role of the practice
      nurse in providing primary health care; and the effective use of the practice
      nurse resource in the 'new' National Health Service. This paper, by drawing on
      material from a qualitative study, specifically examines the type of work
      performed by practice nurses and the factors that influence this. The responses
      of practice nurses, general practitioners, Family Health Service Authority (FHSA)
      advisers, community nurse purchasers and managers of community nursing provider
      units suggest that a consensus on the future development of practice nursing is
      unlikely. The different stakeholders emphasized different issues, reflecting
      their own priorities and backgrounds. Practice nurses' accounts of the future,
      for example, focused on professional issues. General practitioners stressed the
      importance of role development which met their General Medical Service
      responsibilities. Purchasing agencies, provider units and FHSAs adopted a wider
      perspective and were more concerned to develop an effective and integrated
      primary health care service. The tensions generated by their different interests
      and perspectives, and the subsequent organizational and policy initiatives that
      emerge, will provide the context in which the role of practice nurses will be
      negotiated.

PMID- 8876411
TI  - An exploration of parental perception of the nature and level of support needed
      to care for their child with special needs.
AB  - This paper is part of a study attempting to identify parental perception of
      support necessary to care for their child with special needs. The existing
      literature has been analysed, revealing a paucity of studies relating to the
      parents' perception. The study gathered data from questionnaires administered to
      25 randomly selected parents who have children with special needs, exploring
      multi-disciplinary support. The other method used was conducting three semi
      structured interviews, with parents known to the paediatric team in the locality
      being studied. The health professionals input, respite care and overall level of
      support have been studied from the questionnaires. The interviews highlighted
      many areas where the paediatric community nurse could fulfil some of the parents'
      support needs. The response rate was 19 questionnaires returned, covering 21
      children, as two families had two children with special needs. The results
      indicate that half the parents were satisfied with the support they received,
      with the main groups giving support being education and relatives, followed by
      health and social services.

PMID- 8876412
TI  - Perceived professional support and the use of blocking behaviours by hospice
      nurses.
AB  - A prospective study of the impact of training 41 hospice nurses in assessment
      skills was used to test hypotheses that blocking behaviours would be used more
      when patients disclosed feelings and used less when nurses perceived that they
      had satisfactory professional support. Each nurse was asked to assess a patient's
      current problems before and after feedback training and 8 months later. Audiotape
      recordings of these interviews were rated by trained raters. They determined the
      frequency of nurses' responses which had the function of blocking patient
      disclosure and the emotional level of patient disclosure. Before each patient
      assessment each nurse was interviewed and questionnaires administered to measure
      her perceptions of the support she received. Blocking behaviours were most
      evident when patients disclosed their feelings (Kendalls r = 0.36, P < 0.001). In
      interviews containing most patient disclosure of feeling, blocking was
      significantly less (r = -0.24, P < 0.5) when the nurse felt that practical help
      would be available if needed and when the nurse felt that her direct supervisor
      was concerned about the nurse's own welfare (r = -0.37, P < 0.005).

PMID- 8876413
TI  - Making information accessible: developing plain English discharge instructions.
AB  - Discharge education has always been an important role for nurses working in acute
      care contexts. With the advent of case mix funding and subsequent trends towards
      early discharge from hospital, this educational role is assuming increasing
      importance. This paper addresses one aspect of a participatory action research
      study where a group of nurses, working in a paediatric orthopaedic ward, explored
      their discharge education practices and resources. The seemingly large number of
      post-discharge telephone queries received from parents of children treated on the
      ward prompted these nurses to question whether their discharge teaching practices
      were effective. Data collected on these telephone queries identified parental
      concerns regarding the care of their child at home in a plaster. This finding
      prompted group members to explore the ways that written information relating to
      care of the plaster at home might be implicated in the situation. An analysis of
      an existing 'home cast care' discharge instruction sheet raised issues concerning
      the content and language used in such resources. The paper describes the
      subsequent development of a plain English 'plaster care' discharge instruction
      sheet and argues the importance of using plain English in such resources.

PMID- 8876414
TI  - Professional nursing care in Tanzania: a descriptive study of nursing care in
      Ilembula Lutheran Hospital in Tanzania.
AB  - The purpose of this ethnonursing study is to find new knowledge of the
      professional nursing care practised in a Bantu cultural context in Tanzania. The
      main questions are: How do Bantu nurses describe nursing? What components are
      there in professional nursing care in Ilembula Lutheran Hospital? The data were
      collected through participant observation, interviews and personal working
      diaries in Ilembula Lutheran Hospital. Six Tanzanian nurses were interviewed. The
      findings indicated that nursing was based on formal training on one hand, and on
      a natural mother-child relationship on the other hand. The idea of respect
      towards life, which is central to the Bantu philosophy of life, guided nursing
      care. In professional nursing care there emerged curing and caring components.
      Protection, encouragement and comfort were distinguished as the main constructs
      of caring.

PMID- 8876415
TI  - Effects of critical care unit noise on the subjective quality of sleep.
AB  - Nurse researchers have provided evidence that hospital critical care unit (CCU)
      noise may put patients at risk for sleep problems. Technological advances in this
      setting have been described as contributing to this problem. Although data on the
      negative effects of CCU noise on physiological sleep are available, less
      attention has been given to self-reports of the subjective quality of sleep
      following exposure to this stressor. This study hypothesized that subjects
      exposed to CCU sound levels would report poorer subjective sleep than subjects in
      a quieter environment. Sixty female subjects, attempting to sleep overnight in a
      laboratory, were randomly assigned to an experimental group, where they heard an
      audiotape recording of CCU sounds throughout the night, or to a quiet group where
      the audiotape recording of CCU sounds was withheld. A self-rating questionnaire
      was used to assess subjective sleep. The noise condition subjects reported taking
      longer to fall asleep, less time sleeping, more awakenings, poorer quality of
      sleep compared to home, as well as fewer positive and more negative adjectives
      descriptive of sleep. Self-reports of the time spent sleeping and the number of
      negative adjectives descriptive of sleep yielded the greatest number of
      significant correlations with scores for the other measures of sleep, indicating
      that these measures may be more accurate. Data on the quality of dreams yielded
      no difference between groups. The results provide support for the hypothesis that
      CCU sound levels impact negatively on subjective sleep. It was recommended, now
      that CCU sound levels were isolated in the laboratory as a potential stressor,
      that future research should attempt to replicate this study in a hospital CCU.

PMID- 8876416
TI  - Qualified nurses lack adequate knowledge related to oral health, resulting in
      inadequate oral care of patients on medical wards.
AB  - This study tested the theoretical proposition that qualified nurses lack adequate
      knowledge related to oral health, resulting in inadequate oral care of patients
      on medical wards. The research was undertaken in a local district general
      hospital during January 1995. The project aimed to look at local practices of
      qualified nurses related to oral care of patients hospitalized in medical wards.
      Extent of knowledge and current practice of care was examined using a
      questionnaire. Open and closed style questions were used. The sample comprised
      nurses on one elderly care ward and three general medical wards and the sample
      size was 34. The results revealed gaps in knowledge of oral care procedures. In
      particular, a lack of assessment and documentation was highlighted. However, the
      nurses indicated a high level of interest at updating themselves in this area of
      nursing. The limitations of this study are discussed.

PMID- 8876417
TI  - Patient participation: a concept analysis.
AB  - The purpose of this paper is to present an in-depth analysis of the concept of
      patient participation. The analysis was undertaken using the method described by
      Walker and Avant. Patient participation is defined and the critical attributes
      are identified. Model, borderline and contrary cases illustrate what the concept
      is and is not. The meaning of patient participation is compared with patient
      partnership, patient collaboration and patient involvement, three related cases.
      The antecedents and consequences of patient participation are investigated to
      further refine the critical attributes. Empirical referents are illuminated. The
      value of concept analysis in relation to precise communication, critical thinking
      and the advancement of the knowledge base of nursing is discussed.

PMID- 8876418
TI  - How not to clarify concepts in nursing.
AB  - Concept analysis and conceptual clarification form an identifiable genre within
      the nursing literature, with most recent examples drawing on the model proposed
      by Walker & Avant (1988). This paper argues that the Walker & Avant model is
      based on untenable assumptions, and that the writings of those who adopt it
      inevitably contain a serious flaw that vitiates the procedure and renders the
      results arbitrary. In particular, the relationship between concept and theory, a
      topic to which the philosophy of science has devoted much attention, has been
      misunderstood by these authors. Concepts are not the 'building blocks' of theory,
      but the niches created by theory; and any 'conceptual clarification' that
      anticipates theoretical commitment becomes a vacuous exercise in semantics.

PMID- 8876419
TI  - The politics of phenomenological concepts in nursing.
AB  - This paper challenges those nurses who champion Heideggerian phenomenology, by
      outlining some of the possible political consequences of that philosophy. Some
      relationships between phenomenology and fascism are discussed, with special
      reference to anti-humanism and authenticity. Heidegger's commitment to Nazism is
      affirmed and, following the lead of other recent contributions to the debate, it
      is suggested that this was the likely, if not inevitable, result of his
      phenomenological philosophy. It is concluded that, because of its immanent
      fascism, Heideggerian phenomenology is at odds with the general value orientation
      publicly espoused by the nursing profession, and that this may render it not only
      unsuitable as a means of understanding and elaborating nursing knowledge, but
      also actively counter-productive to the conventional aspirations of nurses.

PMID- 8876420
TI  - The concept of hardiness: a brief but critical commentary.
AB  - This paper is a brief critique of the concept of hardiness. While the concept is
      appealing in its potential to elucidate the relationships between stress, health
      and illness, I argue that there are problems with how the concept is defined,
      measured and applied. In particular, the usefulness of the concept is diminished
      through class and gender bias.

PMID- 8876421
TI  - Humans, information and science.
AB  - The use of information forms the basis of nursing policies, standards and
      professional codes of conduct. Although used intuitively, nurses must now also
      grapple empirically with information needs often defined by others, and with the
      technology used to capture and process it. Even the briefest contemplation of
      'information' reveals a truly pervasive concept. Information is ubiquitous. In
      order to care effectively in the so-called 'information age' health care
      professionals need to understand information. This paper is a small contribution
      to that effort, attempting to conjoin the disparate fields of health and the
      information sciences; and the basic sciences upon which they are based. This
      paper explores how definitions of information formulated in computing and
      communication theory relate to health and other aspects of human experience. The
      strategy adopted to achieve this is threefold. First, there is the vexed question
      of defining data, information and knowledge. Second, I consider how communication
      -that essential nursing activity--relates to information, meaning and the
      messages people seek to convey to each other. Thirdly, clinical situations are
      described in an information-oriented manner, using the concepts of 'redundancy'
      and 'entropy'. The conclusion provides an historical perspective.

PMID- 8876422
TI  - CINAHL: an exploratory analysis of the current status of nursing theory
      construction as reflected by the electronic domain.
AB  - Since the 1980s the electronic domain has become the primary method for academic
      and professional communication of research and information. Papers relating to
      theory construction in nursing are a frequently occurring phenomenon within the
      electronic domain. Theory construction provides the underpinning for the
      advancement of professional nursing, facilitating the conceptualization of
      nursing actions leading to theory-based practice and research. The purpose of
      this study was to address the research question, 'What are the similarities and
      differences among theory construction papers that are accessible electronically
      in nursing literature today?' The Cumulative Index to Nursing and Allied Health
      Literature (CINAHL) was accessed to obtain a listing of papers from which an
      overall description of the type of theory construction papers being published in
      the nursing literature today could be determined. A literature search was
      conducted using the description 'theory construction'. Papers were limited to
      publication years from 1990 onwards. A total of 125 papers were obtained and read
      by one of the six authors. Using grounded theory, categories emerged by
      identification of similarities and differences among the papers. The findings are
      discussed here along with suggestions for further study. A second purpose of this
      paper was to present both traditional and non-traditional methods of tapping into
      the electronic domain when searching for assistance with theory construction.

PMID- 8876423
TI  - Concerns of nurse educators regarding the implementation of a major curriculum
      reform.
AB  - This comparative descriptive study used the self-administered stages of concern
      questionnaire, a diagnostic dimension of the Concerns Based Adoption Model, to
      measure the stages of concern of nurse educators (n = 93) at four nursing
      colleges regarding implementation of a new comprehensive basic nursing programme
      (CBNP). Data were analysed using the guidelines from the manual designed by Hall
      et al. The MANOVA was used to measure variations between colleges in high and low
      stages of concern by (a) timing of adoption, (b) perceived level of experience
      with the CBNP and (c) training in use. Differences between colleges in timing of
      adoption were significant in intensity of lower stages of concern (awareness,
      informational, personal and management) only. Concerns of inexperienced users
      were significantly higher than those of experienced users on both lower and
      higher stages of concern. Training in teaching a comprehensive basic nursing
      programme failed to effect significant differences in intensity of concerns among
      nurse educators.

PMID- 8876424
TI  - The study of biology as a cause of anxiety in student nurses undertaking the
      common foundation programme.
AB  - The subject of biology was identified as a cause of anxiety amongst student
      nurses on the common foundation programme (CFP), both verbally and in each of the
      written course evaluations, at a college of nursing and midwifery in the South of
      England. The aim of this study was to identify the major causes of anxiety and
      identify methods of reducing this anxiety in the present students, as well as
      minimizing anxiety in those students commencing their nurse education. Action
      research was considered the most appropriate design for this study. Student nurse
      participation was encouraged throughout the study (n = 66). A modified Delphi
      technique was used to identify and prioritize the causes of anxiety and a student
      quality circles group was formed for the purpose of problem solving by the
      students. This stimulated some of the biology teachers to form biology sub-groups
      to consider the students' proposals. Many changes were implemented. A focus group
      data collection method was used to evaluate the effectiveness of the relevant
      changes for the present students. The meeting was recorded and the tape examined
      for relevant data. The data indicated that although the students perceive biology
      as a subject that causes anxiety they did acknowledge that many of the changes
      made by the teachers were a positive step towards reducing the anxiety. Although
      the results were encouraging, it is noted that to gain a true understanding of
      the effect of the changes, further evaluation would need to be completed. The use
      of triangulation may be considered more appropriate to enhance the quality of the
      data obtained.

PMID- 8876425
TI  - Student evaluation: a performance indicator of quality in nurse education.
AB  - This study, which forms part of a doctoral thesis, is derived from the increasing
      demand for economic models of nurse education as a process within a wider
      economic agenda which converts inputs (e.g. training costs) into outputs (e.g.
      registered nurses). In such a climate the pursuance and determination of quality
      in nurse education should be of fundamental concern to the nursing profession.
      The development of models for evaluation and measurement of quality must take due
      cognisance of the stakeholders' interests and concerns, and student nurses, as
      the consumers of nurse education, must be regarded as major stakeholders. This
      paper describes the use of the course experience questionnaire, an instrument
      designed to investigate the students' perspective on teaching and learning. The
      study incorporates a comparative analysis between Project 2000 students in
      Northern Ireland and students in the apprenticeship programme in the Republic of
      Ireland, from general, psychiatric, sick children's and mental handicap nursing.
      This comparative analysis does provide the nursing profession with a level of
      feedback on which to make decisions in the interest of quality. Nurse teachers
      should examine potential reasons why their programmes are poorly or highly rated
      and the actions that may be required to remedy imperfections on the one hand and
      the actions that may be taken to promote excellence on the other. As nurse
      education continues to forge links with universities, nurse teachers, by adopting
      student evaluation as a performance indicator, can maximize an essential element
      in the web of public accountability.

PMID- 8876427
TI  - A contribution to the emergency care debate in the United Kingdom by the King's
      Fund.

PMID- 8876426
TI  - Managing policy research in nursing.
AB  - This paper draws on the author's experience as a liaison officer in the
      Department of Health, England, to explore the topic of using research in policy
      making. The relationship between the worlds of the researcher and the policy
      maker is discussed, and an example, the research initiative on human resources
      and effectiveness, is chosen to illustrate how research topics are formulated.

PMID- 8876428
TI  - Effect of exposure time on the survival of immature pigs in a confined
      atmosphere.
AB  - Our purpose if to develop a survival strategy for man trapped in a confined
      space. A previous study showed that in the rat there is a critical exposure time
      beyond which hypoxic survival improves. To evaluate the general applicability of
      these findings in the rat and the influence of body size, the effect of exposure
      time on hypoxic survival was studied in immature pigs (26 kg). The pig consumed
      the oxygen in a sealed chamber until hypoxic collapse. We measured blood
      pressure, oxygen consumption, inspired O2 and CO2, minute ventilation, ECG, body
      temperature, and PO2, PCO2 and pH in arterial and venous blood. Five groups of
      pigs were confined in different initial volumes of air, producing total exposure
      times of 0.5, 1.3, 2.3, 4.8 and 6.7 h. There was no significant difference
      between the experimental groups for any of the parameters measured during the
      exposure. Unlike the rat, in the pig there was no "adjustment time" beyond which
      the animal could survive to a lower PIO2. Terminal inspired PO2 increased as a
      function of exposure time. This was related to either hypoventilation or lung
      edema. There was a correlation between the level of carbon dioxide in the blood
      at 60-70 torr inspired oxygen and the terminal PO2. Pigs which failed to clear
      the carbon dioxide succumbed early to hypoxia. In a confined space it is
      preferable to maintain normoxic conditions for as long as possible.

PMID- 8876429
TI  - Multiparameter monitoring and analysis of in vivo ischemic and hypoxic heart.
AB  - We describe a unique in vivo technique which addresses the multifactorial
      function of the heart, i.e., simultaneous measurement of myocardial ion transport
      (two mini-electrode systems to measure K+e and Ca2+e), energy metabolism (NADH
      fluorescence to measure NADH redox state), and coronary flow (laser-Doppler
      perfusion) using a multiprobe assembly (MPA) which contains transducers for all
      measurements. The MPA (which is 6 mm in diameter) was applied to the external
      surface of the heart in an open chest dog model. To test MPA function, myocardial
      ischemia was produced by application of a balloon occluder to the left anterior
      descending coronary (LAD) artery, and hypoxia was produced by changing the
      inspired O2-N2 ratio until the PaO2 was 20-30 torr. The MPA simultaneously
      monitored changes in ion flux, heart metabolism, and tissue perfusion during
      pathophysiological intervention.

PMID- 8876430
TI  - Urinary zinc levels in patients with superficial bladder cancer.
AB  - Urinary zinc levels were determined in 30 healthy people and 42 patients with
      bladder cancer on admission to hospital. There was a significant difference in
      values between the two groups (p < 0.001). The patient group was classified
      according to stage, grade, multiplicity and recurrence. No significant difference
      was found between these groups but each group showed a significant difference in
      comparison with the control group. Patients were treated by transurethral
      resection (TURT) and then classified according to intravesical chemotherapy
      [epirubicin (n = 12), BCG (n = 20), interferon alpha-2 (n = 10)]. One month after
      treatment, 24-h urinary zinc excretion was determined. When this value was
      compared to the excretion of patients before treatment a significant decrease was
      observed (p < 0.001). However, no significant differences were found between the
      treatment groups. The increase in urinary zinc excretion may be related to the
      activity of the tumor and determination may be of value during follow up.

PMID- 8876431
TI  - Characterization of a nucleotide stimulated aspartic proteinase in rat liver
      plasma membranes.
AB  - Inositol phosphoglycan molecules are believed to mediate multiple intracellular
      actions of insulin. They are released from plasma membranes in response to
      insulin binding and are transported into the cell. Release of insulin mediators
      is stimulated by MnATP and MgATP and is inhibited by p-aminobenzamidine. Inositol
      phosphoglycan mediators may be released by a poorly characterized mechanism
      requiring proteolytic cleavage of an attached protein from the mediator and
      phospholipase cleavage of the mediator from its membrane anchor. We examined rat
      liver plasma membranes for proteinase activity stimulated by insulin and MnATP.
      Although we could not demonstrate insulin stimulation, we have found and
      characterized a nucleotide-stimulated aspartic proteinase bound to rat liver
      plasma membranes. We also detected and separated a soluble activating factor for
      the proteinase. The activating factor appears to be a protein with M(r)
      approximately 70 kDa.

PMID- 8876432
TI  - Cadmium induced alterations in somatosensory evoked potentials.
AB  - Pregnant Swiss albino rats were divided into three groups: control (C), cadmium
      (Cd) and non-cadmium (NCd) groups. Control animals received tap water; the Cd
      rats received Cd as CdCl2 in their drinking water during the experimental period,
      while the NCd group was given Cd during pregnancy, and given tap water after
      birth. Twenty-two days after birth, 15 rats (for each group) were taken from
      their mothers and continued to be treated with Cd (Cd group) or tap water (C and
      NCd groups) for an additional 38 days. After the treatment period, somatosensory
      evoked potentials (SEPs) of the three groups were recorded from central (Cz)
      referenced to frontal (Fz) following left posterior tibial nerve (PTN)
      stimulation. Amplitude spectra of SEPs were computed by fast Fourier transform
      (FFT) algorithm. There was a significant amplitude decrease in 1-3.5 Hz in the
      NCd group and 1-3.5 and 14-20 Hz frequency bands of the Cd group compared with
      the control group.

PMID- 8876433
TI  - Membrane properties of complex spike firing neurons of the mouse dorsal cochlear
      nucleus in vitro.
AB  - Intracellular recordings were made from complex spike firing neurons of the mouse
      dorsal cochlear nucleus (DCN) in vitro. The whole cochlear nucleus was dissected
      out and maintained submerged in rapidly flowing artificial cerebrospinal fluid
      (CSF). Recordings were made with current clamp techniques in the presence or
      absence of ion channel blocking drugs tetrodotoxin (TTX, 1 microM),
      tetraethylammonium (TEA, 20 mM), 4-aminopyridine (4-AP, 5 mM) or verapamil (50,
      100, 150, 250 microM). The cells showed both spontaneous firing and responses to
      injections of depolarising current consisting of a mixture of a tall single
      action potential and complexes of 2 to 3 smaller wider action potentials
      superimposed on a plateau depolarisation. The membrane properties were: resting
      membrane potential -68.8 +/- 8.5 mV, cell resistance 54.1 +/- 26.5 M omega, time
      constant 9.6 +/- 5.4 ms and capacitance 0.25 +/- 0.5 nF; the first three
      variables had bimodel distributions. The current/voltage (I/V) relationship at
      membrane below resting was non-linear. Previously published histological evidence
      from the mouse DCN has shown that both cartwheel cells and Purkinje-like neurons
      are present. Both DCN cartwheel cells and cerebellar Purkinje cells are known to
      fire both tall single action potentials and complexes of smaller wider action
      potentials. It is therefore possible that the recordings shown here were made
      from these neuron types. TTX (1 microM) abolished both the tall single and the
      complexes of smaller action potentials, suggesting that the tall single action
      potentials are sodium dependent and possibly that a TTX sensitive sodium channel
      is responsible for the plateau as is suggested for Purkinje cells in the
      cerebellum. Verapamil (100 microM) abolished only the complex action potentials
      and the plateau leaving the tall narrow action potentials intact, which is
      consistent with the smaller complexes being calcium dependent. Higher
      concentrations abolished all spiking activity. TEA and 4-AP used separately both
      caused marked depolarisation to around -20 mV, suggesting that there is a large
      potassium current active at and near resting.

PMID- 8876434
TI  - Probing soft polymeric coatings of a capillary by atomic force microscopy.
AB  - Atomic force microscopy (AFM) has been used to probe the surface of a capillary
      after coating with "soft" polymers, notably polyacrylamides. The aim was the
      investigation of the efficiency of coverage of the silica surface, so as to
      reduce or eliminate the electroosmotic flow (EOF), particularly noxious in the
      separation of macromolecules. The quality of such coating is strongly dependent
      on two variables: temperature and pH. In the first case, progressively higher
      temperatures produce open silica patches, where no polymer seems to be bound. The
      transition from coated to largely uncoated surfaces occurs at 50 degrees C. Also
      the pH of the polymerizing solution strongly affects the coating efficiency.
      Since in all coating procedures the monomer solution is not buffered, addition of
      accelerator (TEMED, N,N,N'N'-tetramethylethylendiamine) induces polymer growth at
      pH 10-11. These pH values generate hydrolysis of the siloxane bridge anchoring
      the bifunctional agent (Bind Silane, onto which the polymer chain should grow) to
      the wall. Thus, coating and de-coating occur simultaneously. Low temperatures
      during polymer growth (typically 10 degrees C) and buffered solutions (pH 7,
      titrated after TEMED addition) ensure a most efficient and thorough coating, with
      virtual elimination of EOF: well coated capillaries exhibit residual EOF values,
      at pH 10, of the order of 10(-7) cm2 V-1 s-1 vs. a standard value for uncoated
      capillaries of the order of 10(-4) cm2 V-1 s-1. The AFM data have been fully
      confirmed by direct measurement of EOF in coated and uncoated capillaries under
      an electric field.

PMID- 8876435
TI  - Enantiomeric separations of basic pharmaceutical drugs by micellar electrokinetic
      chromatography using a chiral surfactant, N-dodecoxycarbonylvaline.
AB  - A novel surfactant with a chiral head group, (R)- or (S)-N-dodecoxycarbonylvaline
      (DDCV), was used to achieve enantiomeric separations of twenty basic
      pharmaceutical compounds by micellar electrokinetic chromatography (MEKC). Most
      of these compounds were beta-agonists (anti-asthmatic, bronchodilators) or beta
      antagonists (anti-hypertension, anti-angina). DDCV can separate polar as well as
      more hydrophobic chiral analytes in the same buffer system. The selectivities for
      these enantiomeric pairs range from 1.03 to 1.23 with good efficiencies.
      Separations utilizing DDCV are easy to optimize and allow for exact enantiomeric
      migration order reversal by switching the enantiomeric form of the surfactant.
      Buffer systems were assessed to minimize Joule heating and to optimize the
      repeatability of parameters such as migration time, relative migration time,
      selectivity, peak areas and area ratios. An electrolyte system consisting of 25
      mM DDCV, 100 mM zwitterionic CHES (2-[N-cyclohexylamino]ethanesulfonic acid) and
      10 mM triethylamine (TEA) was most effective for these runs. The precision for
      migration times, relative migration times and selectivities was better than 1%,
      0.1% and 1% R.S.D., respectively, while the precision for the area ratios ranged
      from 1% to 4%. The possible effect of analyte structure on selectivity,
      efficiency and precision of peak area was studied.

PMID- 8876436
TI  - Micellar electrokinetic chromatography in zero-electroosmotic flow environment.
AB  - Micellar electrokinetic chromatography (MEKC) is conducted in polyacrylamide
      coated capillaries under almost complete suppression of electroosmotic flow. The
      equations of migration and resolution for neutral solutes in this mode of MEKC
      operation are presented. The technique is termed reversed-flow MEKC (RF-MEKC)
      because, in contrast to MEKC in bare-silica capillaries (N-MEKC), solute
      migration order is reversed and solute migration time is inversely proportional
      to micelle concentration. This presents an advantage for the high-efficiency
      separation of extremely and moderately hydrophobic solutes in a short analysis
      time. Examples of the separation of polycyclic aromatic hydrocarbons, aflatoxins
      and dansylated-amino acids are presented using sodium dodecyl sulfate (SDS)
      surfactant. Polycyclic aromatic hydrocarbons are separated using a relatively low
      micelle concentration. The detection sensitivity for these compounds is enhanced
      in two ways. First, the peaks are sharp because of the short analysis time and
      the inertness of the column surface. Second, the fluorescence background and
      Joule's heating are minimal because of the low concentration of SDS and other
      additives needed to affect the separation. While N-MEKC is mainly conducted with
      basic buffers, RF-MEKC can be conducted in basic as well as acidic media as
      illustrated in the separation of 15 dansylated-amino acids at pH 4.2.

PMID- 8876437
TI  - Effects of bile salt structure on chiral separations with mixed micelles of bile
      salts and polyoxyethylene ethers using micellar electrokinetic capillary
      chromatography.
AB  - The chiral resolving abilities of micellar solutions of four different bile salts
      alone and in mixtures with polyoxyethylene-4-dodecyl ether (C12E4) and methanol
      were investigated using MECC. The four bile salts investigated were the
      unconjugated sodium salts of cholic, deoxycholic, chenodeoxycholic and
      ursodeoxycholic acids. The test solutes included verapamil, norverapamil,
      gallopamil, bi-2-naphthol, atenolol and BAYK8644. The relative hydrophobicities
      of the micellar aggregates formed in solutions of binary mixtures of each bile
      salt with C12E4 were investigated by fluorescence spectroscopy using pyrene as a
      probe molecule. The observed enantiomeric resolution for the test compounds using
      these binary mixtures as MECC pseudo-stationary phases was determined.
      Correlations between micellar hydrophobicity for these solutions and chiral
      resolution of these test solutes are presented. The addition of C12E4 with or
      without methanol to solutions of sodium cholate and sodium deoxycholate enhanced
      the chiral resolution observed for compounds containing a longer hydrocarbon
      chain separating some of the major functional groups from the chiral center. The
      pure bile salt solutions generally provided better chiral resolution for the
      compounds where the major functional groups, such as aromatic rings, were closer
      to the chiral center.

PMID- 8876438
TI  - Investigation of a pulsed-laser thermo-optical absorbance detector for the
      determination of food preservatives separated by capillary electrophoresis.
AB  - Thermo-optical absorbance (TOA) detection using a KrF excimer waveguide laser for
      detection of benzoic acid, dehydroacetic acid and sorbic acid separated by
      capillary electrophoresis (CE) was studied. Detection limits were, on average,
      ten times better than those for on-column UV absorbance methods with CE, and two
      or more times better than those for UV absorbance with HPLC. The influence of
      increased laser power on TOA detection sensitivity was found to be strong for
      benzoic and dehydroacetic acids but quite weak for sorbic acid. It was discovered
      that photoisomerization of sorbic acid (2,4-hexadienoic acid) occurred readily in
      the detection volume at moderate laser powers (P(ave) = 3 mW) and increased with
      slow electroosmotic flows (< 6 cm/min). The TOA method described here shows
      improved detection sensitivity for CE analyses of compounds having only weak
      absorptivities (< 5% of maximum) at lambda = 248 nm, and thus demonstrates its
      utility for determination of a variety of analytes in a single separation.

PMID- 8876439
TI  - Capillary electrophoresis for clinical problem solving: analysis of urinary
      diagnostic metabolites and serum proteins.
AB  - Many clinical laboratories employ gas chromatography-mass spectrometry (GC-MS)
      and high-performance liquid chromatography (HPLC) to detect abnormal compounds
      occurring in urine and serum due to disease. The methods, particularly GC-MS,
      often require laborious sample pre-treatment, and separation times may exceed an
      hour. We describe the use of capillary electrophoresis (CE) equipped a with a
      diode-array detector in an attempt to improve the efficiency of an analytical
      system routinely used for diagnosis of human metabolic disease. It was found that
      urine samples could be injected directly onto the CE instrument without any pre
      treatment, and over 50 metabolites were separated in 15 min. Identification of
      abnormal metabolites was based on migration times and characteristic diode-array
      spectra. The method readily diagnosed adenolysuccinase deficiency, 5
      oxoprolinuria, propionic acidemia and disorders have orotic acid as diagnostic
      metabolite (e.g. the HHH-syndrome). The results show that CE may become a useful
      additional tool for diagnosis of metabolic disease. In a different project CE was
      used to study sera from the Janus-bank. This large serum bank comprises samples
      collected at intervals from nearly 300,000 blood donors. As the sera are stored
      at -25 degrees C and not at a lower temperature, a major concern has been the
      stability of the specimens. GC-MS, 2D-protein electrophoresis, certain
      immunological assays and enzyme measurements have previously been used to
      evaluate the stability of the sera. We can now also show that the protein
      profile, as determined by CE, is remarkably stable even after 22 years of
      storage. The results moreover confirmed that the CE-method and traditional gel
      electrophoresis gave almost identical results, except for small amounts of
      fibrinogen which did not show up on the CE-pattern.

PMID- 8876440
TI  - Drug identification in biological matrices using capillary electrophoresis and
      chemometric software.
AB  - Drugs and their metabolites in biological specimens are analyzed by a variety of
      techniques. Capillary electrophoresis could provide another useful approach
      because of its unique selectivity and high resolving power. For routine use,
      however, rugged methods must be developed and combined with detection that
      confirms peak purity and identity in difficult sample matrices, such as, urine.
      In this study, capillary electrophoresis is used with diode array detection, and
      chemometric software is employed for spectral analysis. The software includes a
      series of chemometric tools. Principle Component Analysis and Iterative Target
      Transform Factor Analysis are used to inspect each electropherogram for spectral
      homogeneity of the peaks and to deconvolute comigrations. These algorithms are
      used to confirm the assay results. This approach is tested and demonstrated for
      the analysis of amphetamine and common interferences in human urine.

PMID- 8876441
TI  - Design and optimization of a capillary electrophoretic mobility shift assay
      involving trp repressor-DNA complexes.
AB  - An investigation of DNA-protein interactions by capillary electrophoresis (CE)
      with laser fluorometric detection is performed that combines the rapid and
      minimal sample consumption methods of CE with the selective separation influence
      of mobility shift assays. An inspection of the well characterized interaction
      between the trp repressor of Escherichia coli and the trp operator (DNA) is the
      basis of the assay. The use of fluorescently tagged operator not only lends
      itself to laser-induced fluorescence detection but also precludes the use of
      radiolabeled detection. It is demonstrated that composition and pH of the running
      buffer are critical for maximized efficiency and resolution of operator from the
      repressor-operator complex. Quantitative studies showed reaction of repressor
      with operator resulted in the diminishing of free operator signal and the
      simultaneous creation of the repressor-operator peak that is well resolved from
      the free operator. Also examined was the ability to perform qualitative studies
      involving non-specific interactions between the operator and a complex protein
      sample. It is shown that the specificity of operator for repressor can be used to
      selectively separate the repressor from a complex sample that includes non
      specific proteins.

PMID- 8876442
TI  - Measurement of 60Co-gamma ray-induced DNA damage by capillary electrophoresis.
AB  - Capillary electrophoresis was employed in this study to monitor 60Co-gamma ray
      induced damage to a 1 kb DNA ladder which consists of restriction fragments
      ranging from 75 to 12,000 bp. DNA samples (0.5 mg/ml) were exposed to 0-60 Gy of
      gamma-radiation in the presence and absence of 110 mumol/l ethidium bromide (EB).
      The analysis showed peak broadening without significant changes in the size
      distribution of irradiated fragments. Radiation-induced conformational changes
      may account for this peak broadening. EB addition caused small increases in the
      retention times of DNA fragments without affecting the overall DNA damage. This
      indicates that the presence of intercalated EB during radiation will not
      stabilize the DNA against 60Co-gamma ray-induced damage.

PMID- 8876443
TI  - Analysis of laser-induced plasmic DNA photolysis by capillary electrophoresis.
AB  - Capillary electrophoresis (CE) was used to monitor the laser-induced conversion
      of supercoiled pKOL8UV5 plasmid DNA into nicked conformers. The plasmid samples
      (0.1 mg/ml) were incubated in the absence or presence of 110 mumol/l ethidium
      bromide (EB) and then exposed to 100 J of argon laser radiation (488 nm). The
      nicked, open circular conformers were separated from the supercoiled DNA by a 15%
      increase in retention time. Approximately 90% of the control DNA was in the
      supercoiled form. Laser radiation in the presence of EB caused complete
      conversion of the supercoiled plasmid DNA into nicked conformers. Laser-induced
      fluorescence CE (LIF-CE) was about 100-fold more sensitive than UV-CE in the
      detection of these conformers. Agarose gel electrophoresis confirmed these
      findings and showed the presence of the nicked plasmid conformers. Based on these
      comparisons, CE is an efficient analytical tool for the identification of laser
      induced conformational changes in plasmid DNA.

PMID- 8876444
TI  - Use of capillary zone electrophoresis for analysis of imidodipeptides in urine of
      prolidase-deficient patients.
AB  - Prolidase deficiency (PD) is characterized by massive urinary excretion of
      imidodipeptides X-Pro and X-Hyp. We report the applicability of capillary zone
      electrophoresis to urinary imidodipeptide determination. The protocol is fast,
      simple, reliable, only small amounts of sample are required and there is minimal
      sample preparation. Electropherograms of urine samples from control subjects and
      four patients with prolidase deficiency were compared. The presence of
      imidodipeptides normally absent in urine was evident in patients' urine. Further
      analysis of urine samples enabled identification of excreted imidodipeptides and
      the pattern of excretion appeared to be heterogeneous for different patients.
      This method appears to be useful for identification of imidodipeptides in
      biological samples, as an efficient aid in diagnosis of PD, and as a method for
      providing more information about this disease.

PMID- 8876445
TI  - Automated polymerase chain reaction product sample preparation for capillary
      electrophoresis analysis.
AB  - The analysis of crude polymerase chain reaction (PCR) products by capillary
      electrophoresis (CE) is often compromised due to the presence of a high
      concentration of salt. Salt interferes with the electrokinetic injection and
      induces localized heating within the column; hence, PCR products must be desalted
      or cleaned-up prior to CE analysis. A variety of commercial clean-up systems are
      available that have been traditionally used to prepare PCR products for cloning,
      sequencing and digestion with restriction enzymes. These systems were tested for
      their effectiveness in preparing PCR products for CE analysis and were evaluated
      based on CE resolution, salt removal, DNA recovery, processing time and cost. One
      particularly effective clean-up system, membrane dialysis, was automated using a
      robotic workstation.

PMID- 8876446
TI  - Analysis of ibuprofen in serum by capillary electrophoresis.
AB  - A rapid method for analysis of the analgesic drug ibuprofen in serum by capillary
      zone electrophoresis in a borate buffer 160 mmol/l pH 8.5 is described. The
      method involves deproteinization with acetonitrile to remove serum proteins
      followed by direct injection on the capillary. The recoveries of standards added
      to the serum were 84-92%. The method is suited for analysis of samples with
      concentrations > 10 mg/l. Many other analgesics such as ketoprofen, daypro and
      salicylates can also be determined by this method.

PMID- 8876447
TI  - Serum lamotrigine analysis by capillary electrophoresis.
AB  - Lamotrigine, a new antiepileptic drug, is analyzed by capillary zone
      electrophoresis. Samples were deproteinized with acetonitrile containing an
      internal standard, acidified with dilute acetic acid and injected into the
      capillary. The drug migrated rapidly with the cationic compounds in about 3.5 min
      far from any interfering substances. The test was linear between 0.5-10 mg/l. The
      analysis time was about 5 min. The CE values correlated well with an HPLC method
      (r = 0.97; n = 35). The mean serum concentration of 121 patients on this drug was
      3.7 mg/l. Incubating the serum with beta-glucuronidase for 1 h increased the peak
      height of lamotrigine by about 24%.

PMID- 8876448
TI  - Analysis of cathepsin D from breast tissues by capillary electrophoresis.
AB  - A rapid and simple method for analyzing cathepsin D in breast tissue based on
      capillary zone electrophoresis (CZE) is described. After incubating the tissue
      extracts with hemoglobin as a substrate, a specific peptide is cleaved and
      separated by CZE in less than 5 min. This peptide is not produced by the action
      of pepsin or trypsin. It is inhibited by the addition of pepstatin, a specific
      inhibitor for cathepsin D. Human hemoglobin acted as a better substrate than
      bovine hemoglobin. The test compared well to a radioimmunoassay. We have shown
      that peptides can be stacked by the use of acetonitrile. The method demonstrates
      the advantages of CZE for assay of proteolytic enzymes in general.

PMID- 8876449
TI  - GABAergic synapses in the antennal lobe and mushroom body of the locust olfactory
      system.
AB  - To help elucidate the role of inhibitory feedback in the genesis of odour-evoked
      synchronization of neural activity, we investigated the distribution of gamma
      aminobutyric acid (GABA)ergic synaptic terminals in the antennal lobes (AL) and
      mushroom bodies (MB) of the locust olfactory system. Electron-microscopy,
      intracellular horseradish peroxidase labelling, and immunocytochemistry were
      combined to assess the distribution of GABAergic synapses, using established
      methods (Leitch and Laurent [1993] J. Comp. Neurol. 337:461-470). In the AL, GABA
      immunoreactive presynaptic terminals contacted both immunoreactive and
      immunonegative profiles. Conversely, GABA-immunoreactive profiles received direct
      input from both reactive and negative terminals. The tract containing the axons
      of the projection neurons that run from the AL to the MB contained about 830
      axons of fairly uniform size, none of which was immunoreactive for GABA. In the
      calyx of the MB, large immunoreactive terminals contacted very-small-diameter
      profiles thought to belong to the Kenyon cells (KCs). This was confirmed by
      combining immunocytochemistry with intracellular HRP-labelling of KCs. KCs were
      not immunoreactive for GABA. Although some GABAergic contacts were made onto the
      spiny profiles of KCs, others were made onto their dendritic shafts. Large GABA
      immunoreactive profiles were also found to contact large negative profiles that
      were presynaptic to KC terminals. This suggests that KC dendrites can be both pre
      and post-synaptically inhibited in the calyx. The MB pedunculus contained ca.
      50,000 tightly packed KC axons, showing conspicuous en passant and often
      reciprocal synaptic contacts between neighbouring axons. KC axons were
      immunonegative, but received direct input from, and contacted directly, large
      immunoreactive profiles running across or along the KC axons. In the alpha- and
      beta-lobes of the MB, connections similar to those in the pedunculus were seen
      with two main differences: (1) The density of synaptic profiles was higher,
      giving on occasion numerous serially connected profiles in a single section; (2)
      large immunonegative profiles with dense-core vesicles were abundant and were
      frequently presynaptic to GABAergic processes and to very-small-diameter profiles
      which possibly belong to KCs. These results are discussed in the context of the
      known physiological data on olfactory processing in these complex circuits.

PMID- 8876451
TI  - Afferent and efferent connections of the habenula in the rainbow trout
      (Oncorhynchus mykiss): an indocarbocyanine dye (DiI) study.
AB  - The habenula is a conserved structure in the brain of vertebrates. With the aim
      of further understanding of the evolution of the habenular system in vertebrates,
      we studied the afferent and efferent connections of the habenula of the rainbow
      trout. Experiments included application of the carbocyanine dye 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) into the habenula,
      telencephalon, pineal organ, posterior tubercle, and interpeduncular nucleus
      (IPN). The results obtained reveal a consistent pattern of habenular connections.
      Most afferents originate from three nuclei, one extending from the preoptic
      region to the rostral thalamus (the entopeduncular nucleus), the second located
      in the region of the hypothalamus-posterior tubercle and consisting of large
      bipolar cells (tuberculohabenular nucleus), and the third in the preoptic region
      (preoptic nucleus). A few large neurons of the locus coeruleus appeared to be
      labeled in some cases. The trout habenula also receives pineal and parapineal
      projections. Small labeled glial cells were observed in the thalamus around the
      fasciculus retroflexus and, sometimes, around the IPN. The most conspicuous
      efferents coursed in the fasciculus retroflexus to the IPN, the isthmal raphe,
      and the central gray. The existence of olfactohabenular or habenulotelencephalic
      projections is discussed.

PMID- 8876450
TI  - Mechanisms underlying the neuropathological consequences of epileptic activity in
      the rat hippocampus in vitro.
AB  - Blockage of gamma-aminobutyric acid (GABA)ergic synaptic transmission in mature
      hippocampal slice cultures for a period of 3 days with convulsants was shown
      previously to induce chronic epileptiform activity and to mimic many of the
      degenerative changes observed in the hippocampi of epileptic humans. The cellular
      mechanisms underlying the induction of this degeneration were examined in the
      present study by comparing the effects of GABA blockers with the effects produced
      by the K+ channel blocker tetraethylammonium (2 mM). Both types of convulsant
      caused a comparable decrease in the number of Nissl-stained pyramidal cells in
      areas CA1 and CA3. No significant cell loss was induced by tetraethylammonium
      when epileptiform discharge was reduced by simultaneous exposure of cultures to
      tetrodotoxin (0.5 microM) or to the anticonvulsants pentobarbital (50 microM) or
      tiagabine (50 microM). We conclude that this degeneration was mediated by
      convulsant-induced epileptiform discharge itself. The hypothesis that N-methyl-d
      aspartate (NMDA) receptor-mediated excitotoxicity underlies cell death in this
      model was tested by applying convulsants together with specific antagonists of
      glutamate receptors. Whereas coapplication of antagonists of both non-NMDA and
      NMDA receptors strongly reduced the degeneration induced by the convulsants,
      application of either class of antagonist alone did not. Application of exogenous
      NMDA produced potent cell death, and this degeneration was blocked by the NMDA
      receptor antagonist methyl-10,11-dihydro-5-H-dibenzocyclohepten-5,10-imine (MK
      801). Convulsants also induced a loss of dendritic spines that could be partially
      prevented by NMDA or non-NMDA receptor antagonists. We conclude that NMDA
      receptor activation is not solely responsible for the neuronal pathology
      resulting as a consequence of epileptiform discharge.

PMID- 8876452
TI  - Detection of jun but not fos protein during developmental cell death in
      sympathetic neurons.
AB  - A large proportion of neurons die during normal development of the nervous system
      via an active process known as apoptosis. We counted the total number of neurons
      and apoptotic neurons in the superior cervical ganglion of the GH Wistar rat
      strain, which possesses a neurotrophic deficit leading to excessive perinatal
      cell death, and in its normal counterpart (N) by using the optical disector
      method to quantify the extent of apoptosis during postnatal development. Total
      neuron numbers fell between postnatal days 3 and 14 by 10 and 40% in N and GH,
      respectively. In GH ganglia, 1.5% of neurons were apoptotic at any given time, as
      determined by the presence of condensed chromatin clumps. Some types of cell
      death have been associated with expression of the immediate-early genes c-fos and
      c-jun. Therefore, we used histological and immunocytochemical techniques to
      characterise individual neurons and to detect the products of these immediate
      early genes during developmental cell death. All apoptotic cells were
      immunopositive for c-jun protein, whereas no c-jun protein was detected in
      nonapoptotic cells. Conversely, members of the fos family of transcription
      factors were detected in the nucleus of 60% of nonapoptotic cells but in only a
      minor proportion of cells undergoing apoptosis. These results indicate that c-jun
      occurs in neurons that are committed to die. This is the first situation in which
      the presence of jun protein has been correlated with normal programmed cell death
      in individual apoptotic neurons.

PMID- 8876453
TI  - Thalamic collaterals of corticostriatal axons: their termination field and
      synaptic targets in cats.
AB  - Branched cortical projections to the thalamus and striatum were investigated in
      cats by injecting the retrograde-anterograde tracer biotinylated-dextran amine
      (BDA) into the caudate nucleus. These injections gave rise to plexuses of labeled
      fibers and varicosities in widespread thalamic territories. For instance, the
      lateroposterior nucleus and pulvinar (LP-PUL) mostly contained thick axons that
      contributed clusters of large-sized varicosities, each forming multiple
      asymmetric synapses, usually with vesicle-filled dendrites. In contrast, the
      intralaminar nuclei mostly contained thin axonal segments that emitted small en
      passant varicosities that formed single asymmetric synapses with spines. Because
      the caudate nucleus does not project to the thalamus, this labeling had to arise
      from a neuronal population with branching axons to both structures. Previous
      findings pointed to three possible sources: brainstem monoaminergic cells,
      intralaminar thalamic neurons, and corticostriatal cells. The first candidate
      could be ruled out because monoaminergic neurons contribute small-sized terminals
      that usually lack membrane specializations. The second possibility was discarded
      because retrograde tracer injections into the LP-PUL did not give rise to
      retrograde labeling in the intralaminar nuclear complex but to massive retrograde
      labeling in deep layers of cortical areas 5 and 7. Therefore, we concluded that
      the thalamic anterograde labeling originated from corticostriatal neurons, with
      axons branching to the thalamus. In keeping with this conclusion, Phaseolus
      vulgaris-leucoagglutinin (PHA-L) injections into cortical areas 5-7 labeled a
      group of thick corticothalamic fibers that ended in clusters of large boutons in
      the LP-PUL. These PHA-L-positive terminals were indistinguishable from those
      labeled after injections of BDA into the caudate nucleus, but they were easy to
      distinguish from the typical corticothalamic fibers. These findings indicate that
      the cerebral cortex could coordinate the activity of the striatum and the
      thalamus via a rich axonal network that collateralizes to both structures. The
      extent and synaptic organization of this branched projection impose a revision of
      the traditional scheme of thalamic connectivity.

PMID- 8876454
TI  - Secondary vestibulo-oculomotor projections in larval sea lamprey: anterior
      octavomotor nucleus.
AB  - The ventral octavolateral area of lampreys contains three nuclei: the anterior,
      intermediate and posterior octavomotor nuclei, formed of large neurons that are
      contacted by thick primary vestibular fibres. We used horseradish peroxidase
      (HRP) or fluorescein-dextran-amine (FDA) labelling to study the projections of
      the anterior octavomotor nucleus (AON) in the larval sea lamprey, Petromyzon
      marinus. The tracers were injected either in the AON, the oculomotor nucleus or
      the rostralmost spinal cord. HRP injection in the AON labelled thick axons that
      coursed to the basal mesencephalic tegmentum, where most decussate and project to
      the oculomotor nucleus and the third Muller cell. Electron microscopy confirmed
      that AON axons contact with the contralateral third Muller cell and with
      oculomotor neurons. Some AON axons run in the mesencephalic tegmentum and the
      ventral diencephalon. An AON axon was observed to run close to the axon of the
      contralateral third Muller cell, establishing what appeared to be en passant
      contacts. HRP injection in the AON also revealed commissural fibres projecting to
      the contralateral octavolateral area. HRP or FDA injections in the oculomotor
      nucleus labelled both large and small neurons of the AON, mostly contralateral to
      the injection site, as well as of cells in the intermediate octavomotor nucleus,
      mainly ipsilateral. HRP injection in the AON or in the rostral spinal cord did
      not reveal any projections from the AON to the spinal cord. Our results indicate
      that the pattern of octavo-oculomotor connections in the lamprey is different
      from that observed in other vertebrates.

PMID- 8876456
TI  - Distribution and coverage of beta cells in the cat retina.
AB  - We have reexamined the retinal distribution and dendritic field dimensions of
      beta cells in the cat retina. Beta cells were labeled by retrograde transport
      from the A-layers of the lateral geniculate nucleus and distinguished from alpha
      cells on the basis of soma size. Dendritic fields of beta cells were visualized
      by intracellular staining in vitro. The fraction of cat ganglion cells that were
      beta cells varied with retinal location. Except near the area centralis, beta
      cells represented about half of all ganglion cells in the nasal hemiretina. They
      contributed as heavily as the other major ganglion cell classes to the nasal
      visual streak. In and near the area centralis and in the temporal retina, beta
      cells represented about two-thirds of all ganglion cells. The areas of beta cell
      dendritic fields were reciprocally related to beta cell density. For example,
      they were 3-fold smaller within the visual streak than at matched eccentricities
      outside it. For many cells, we could estimate both local beta cell density and
      dendritic field area. Coverage factor (dendritic field area x local density)
      remained constant at about 4 despite 100-fold variations in beta cell density,
      and was independent of eccentricity, nasotemporal location, or position relative
      to the visual streak. Analysis in terms of sampling theory suggests that the beta
      cell array is matched to X-cell spatial resolution so as to optimize acuity. The
      beta cell distribution and its systematic reflection in dendritic architecture
      predict acuity levels that apparently correlate well with actual visual
      performance across the cat's visual field.

PMID- 8876455
TI  - Embryonic development of the enteric nervous system of the grasshopper
      Schistocerca americana.
AB  - The enteric nervous system (ENS) of the grasshopper Schistocerca americana is
      organized into four ganglia located in the foregut (the dorsal unpaired frontal
      and hypocerebral ganglia, and the paired ingluvial ganglia), and two plexuses
      that innervate the foregut and midgut. A dorsomedial recurrent nerve and two
      lateral esophageal nerves connect the ganglia. The midgut plexus is arranged in
      four nerves running along the midgut surface. In this study, we have focused on
      the embryonic development of the grasshopper ENS; we have studied the
      proliferation pattern, morphogenesis, and some aspects of neuronal
      differentiation by using a number of specific molecular markers. The grasshopper
      ENS develops early in embryogenesis (25-30%) from three neurogenic zones (NZs)
      located on the roof of the stomodeum. These NZs slightly invaginate from an
      epithelial placode. The expression pattern of specific cell surface proteins and
      the analysis of the mitotic activity showed that NZs cells delaminate from the
      epithelium, become neuronal precursors, divide symmetrically, and then actively
      migrate to their final position in the enteric ganglia or plexuses. The
      grasshopper enteric ganglia are composed of mixed populations of cells from
      different NZs. The foregut and midgut plexuses are formed by the dispersal of
      cells from the developing hypocerebral and ingluvial ganglia. The main ENS nerves
      are pioneered by axons extending anteriorly from hypocerebral and ingluvial
      neurons. The insect ENS exhibits an enormous variation in design. Several
      features of the grasshopper program of neurogenesis and pattern of cell migration
      are compared to other insects, and some evolutionary implications are discussed.

PMID- 8876457
TI  - Structural features of crayfish phasic and tonic neuromuscular terminals.
AB  - We examined the fine structure of terminals of the phasic and tonic excitatory
      axon to the crayfish limb extensor muscle. The phasic terminals are known to
      release 50-100 times more transmitter for a small length of terminal for a single
      impulse. Phasic terminals labeled with horseradish peroxidase (HRP) were
      relatively thin and contained a single unbranched mitochondrion; tonic terminals
      were much thicker, and their varicosities contained several multibranched
      mitochondria. Tonic terminals devoted a larger proportion of their total volume
      to mitochondria. The percentage volume of clear synaptic vesicles was slightly
      higher in phasic axon terminals, but as the tonic axon terminals were fivefold
      larger in volume, the total synaptic volume is much greater in tonic than phasic
      terminals. The number of synapses per length of terminal, and the total number of
      active zones per length of terminal, were greater for tonic terminals, and
      individual synapses were, on average, slightly larger in surface contact area for
      tonic terminals. In contrast, individual active zones were, on average, longer in
      phasic synapses. A higher proportion (50%) of phasic synapses had multiple active
      zones than was the case for tonic synapses (16%), and pairs of closely spaced
      active zones were more frequently found on phasic synapses. These findings
      clearly rule out synapse and active zone number as a factor contributing to
      higher transmitter output, but suggest that active zone size and synaptic
      complexity, as evidenced by multiple closely spaced active zones in a single
      synapse, are likely to play a causal role in the greater transmitter release of
      the phasic terminal. Even synapse complexity would not be enough to account fully
      for the large difference in terminal transmitter output, and additional factors
      may include electrical and biochemical differences.

PMID- 8876458
TI  - Initial formation and secondary condensation of nerve pathways in the medicinal
      leech.
AB  - Invertebrates have proved to be important experimental systems for examining
      questions related to growth cone navigation and nerve formation, in large part
      because of their simpler nervous systems. However, such apparent simplicity can
      be deceiving because the final stereotyped patterns may be the result of multiple
      developmental mechanisms and not necessarily the sole consequence of the pathway
      choices of individual growth cones. We have examined the normal sequence of
      events that are involved in the formation of the major peripheral nerves in leech
      embryos by employing (1) an antibody directed against acetylated tubulin to label
      neurons growing out from the central nervous system, (2) the Lan3-2 antibody to
      label a specific population of peripheral neurons growing into the central
      nervous system, and (3) intracellular dye filling of single cells. We found that
      the mature pattern of nerves was characterized by a pair of large nerve roots,
      each of which branched into two major tracts. The earliest axonal projections did
      not, however, establish this pattern definitively. Rather, each of the four
      nerves initially formed as discrete, roughly parallel tracts without bifurcation,
      with the final branching pattern of the nerve roots being generated by a
      secondary condensation. In addition, we found that some of the nerves were
      pioneered in different ways and by different groups of neurons. One of the nerves
      was established by central neurons growing peripherally, another by peripheral
      neurons growing centrally. These results suggest that the formation of common
      nerves and neuronal pathfinding in the leech involves multiple sets of growth
      cone guidance strategies and morphogenetic mechanisms that belie its apparent
      simplicity.

PMID- 8876459
TI  - Three classes of inhibitory amino acid terminals in the cochlear nucleus of the
      guinea pig.
AB  - Electron microscopic postembedding immunocytochemistry was used to analyze and
      assess the synaptic distribution of glycine (GLY) and gamma-amino butyric acid
      (GABA) immunoreactivities in the guinea pig cochlear nucleus (CN). Three classes
      of endings were identified containing immunolabeling for glycine, GABA, or both
      glycine and GABA (GLY/GABA). All classes were similar in that the terminals
      contained pleomorphic vesicles and formed symmetric synapses with their
      postsynaptic targets. A fourth class, which labeled with neither antibody,
      contained round vesicles and formed asymmetric synapses. Glycine endings
      predominated in the ventral CN, while GLY/GABA endings were prevalent in the
      dorsal CN. GABA endings were the least common and smallest in size. Glycine,
      GLY/GABA, and GABA endings differed in their proportions and patterns of
      distribution on the different classes of projection neurons in the CN, including
      spherical bushy, type I stellate/multipolar, and octopus cells in the ventral CN
      and fusiform cells in the dorsal CN. The vast majority of anatomically-defined,
      putative inhibitory endings contain GLY, GABA, or both, suggesting that most of
      the inhibition in the cochlear nucleus is mediated by these three cytochemically
      and, probably, functionally distinct classes of endings. The results of this
      study also suggest that a large proportion of the GABA available for inhibition
      in the CN coexists in terminals with glycine.

PMID- 8876460
TI  - Immunolocalization of muscarinic acetylcholine subtype 2 receptors in rat
      cochlear nucleus.
AB  - It has been suggested that cholinergic effects in the rat cochlear nucleus (CN)
      are mediated by muscarinic acetylcholine receptors. In this study,
      immunohistochemistry for muscarinic subtype 2 (m2) receptors using a monoclonal
      subtype-specific antibody (Levey et al. [1995] J. Comp. Neurol. 351:339-356)
      revealed an m2-like system in the rat CN. A prominent lamina of m2-immunoreactive
      fibers and puncta was located in a subgranular layer of the caudal anteroventral
      cochlear nucleus (AVCN) and the posteroventral cochlear nucleus (PVCN). The
      superficial granular layer of the rostral AVCN and the medial sheet region also
      contained notable immunoreactivity for m2. Some labeled somata and their
      processes were found in magnocellular regions of the ventral CN. A network of
      neurites and puncta was located in the fusiform soma and deep layers of the
      dorsal CN. The olivocochlear bundle and its branches to the CN were also m2
      immunoreactive and possibly contributed m2-labeled fibers and terminals to the
      CN. Some similarities and some differences were found between this m2 receptor
      distribution pattern and previous results for choline acetyltransferase (ChAT),
      acetylcholinesterase (AChE), and muscarinic acetylcholine receptor
      immunohistochemistry and binding in the CN. The results suggest that m2 receptors
      that are located both pre- and postsynaptically mediate many cholinergic effects
      in the rat CN.

PMID- 8876461
TI  - Structure, development, and maintenance of the nerve net of the body column in
      Hydra.
AB  - The anatomy and developmental dynamics of the nerve net in the body column of
      Hydra viridissima were examined immunocytochemically with a monoclonal antibody
      (CC04) that recognizes an antigen in nerve cells and with an antiserum against
      vasopressin. CC04+ neuron cell bodies, their neurites, and vasopressin-like
      immunoreactive (VLI+) neurites could be clearly visualized on whole-mount
      preparations. All neurites of the CC04+ neurons in the body column were VLI+.
      However, only half of the VLI+ neurites in the body column were CC04+.
      Immunocytochemical analysis of macerated preparations showed that half of the
      neurons in the gastric region of the body column were CC04+. These results
      suggest that most of the neurons in the gastric region are VLI+. The density of
      the VLI+ neurites was uniform along the entire length of the body column. The
      CC04+ neuron density in the gastric region remained constant at all stages of
      asexual development and during foot regeneration. After pulse-labeling with 5
      bromo-2'-deoxyuridine (BrdU), CC04+ neurons with labeled nuclei appeared in the
      body column. We conclude that neuron density in the gastric region is maintained
      at a constant value by insertion of new neurons in parallel with continuous
      epithelial cell division.

PMID- 8876462
TI  - Increased vulnerability to demyelination in streptozotocin diabetic rats.
AB  - Demyelination is a prominent feature in nerve biopsies of patients with diabetic
      neuropathy. The mechanism is unknown because diabetic rodents, unlike humans, do
      not consistently develop segmental demyelination. We examined how diabetes
      influences toxicant-induced demyelination, remyelination, Schwann cell nerve
      growth factor receptor (p75) expression, and endoneurial macrophage
      apolipoprotein E (apo E) synthesis in diabetic rats. Postnatal day 17 (P17) rats
      were given 110 mg/kg streptozotocin intraperitoneally and then fed a diet
      containing metallic tellurium (Te) from P20 to P27 to induce demyelination.
      Transverse electron micrographs and immunostained longitudinal cryosections were
      prepared from sciatic nerve during demyelination and remyelination. Diabetic rats
      had a mean serum glucose concentration of 490 mg/dl and consumed equivalent doses
      of peroral Te. The number of demyelinated fibers in electron micrographs was
      increased significantly by 17% (P < .0011). Endoneurial density of p75-stained
      Schwann cells was increased in diabetic rats in proportion to the increased
      number of injured internodes. Density of apo E- and ED1-positive macrophages also
      was significantly increased in diabetes. There was no delay in macrophage myelin
      clearance. and remyelination was not compromised. Increased Schwann cell
      vulnerability to stress, by increasing the turnover rate of myelinated units, may
      explain why myelin defects accumulate after long-standing diabetes.

PMID- 8876463
TI  - Monosynaptic projections from the nucleus tractus solitarii to C1 adrenergic
      neurons in the rostral ventrolateral medulla: comparison with input from the
      caudal ventrolateral medulla.
AB  - The rostral ventrolateral medulla (RVL) contains reticulospinal adrenergic (C1)
      neurons that are thought to be sympathoexcitatory and that form the medullary
      efferent limb of the baroreceptor reflex pathway. The RVL receives direct
      projections from two important autonomic regions, the caudal ventrolateral
      medulla (CVL) and the nucleus tractus solitarii with immunocytochemical
      identification of C1 adrenergic neurons in the RVL to compare the morphology of
      afferent input from these two autonomic regions into the RVL. NTS (n = 203) and
      CVL (n = 380) efferent terminals had similar morphology and vesicular content,
      but CVL efferent terminals were slightly larger than NTS efferent terminals.
      Overall, efferent terminals from either region were equally likely to contact
      adrenergic neurons in the RVL (21% for NTS, 25% for CVL). Although efferents from
      both regions formed both symmetric and asymmetric synapses, NTS efferent
      terminals were statistically more likely to form asymmetric synapses than CVL
      efferent terminals. CVL efferent terminals were more likely to contact adrenergic
      somata than were NTS efferents, which usually contacted dendrites. These findings
      1) support the hypothesis that a portion of NTS efferents to the RVL may be
      involved in sympathoexcitatory, e.g., chemoreceptor, reflexes (via asymmetric
      synapses), whereas those from the CVL mediate sympathoinhibition (via symmetric
      synapses); and 2) provide an anatomical substrate for differential postsynaptic
      modulation of C1 neurons by projections from the NTS and CVL. With their more
      frequent somatic localization, CVL inhibitory inputs may be more influential than
      excitatory NTS inputs in determining the discharge of RVL neurons.

PMID- 8876464
TI  - Cellular distribution of neurotensin receptors in rat brain: immunohistochemical
      study using an antipeptide antibody against the cloned high affinity receptor.
AB  - Receptors for the neuropeptide, neurotensin, were localized by
      immunohistochemistry in the rat brain by using an antibody raised against a
      sequence of the third intracellular loop of the cloned high affinity receptor.
      Selective receptor immunostaining was observed throughout the brain and
      brainstem. This immunostaining was totally prevented by preadsorbing the antibody
      with the immunogenic peptide. The regional distribution of the immunoreactivity
      conformed for the most part to that of [3H]- or [125I]-neurotensin binding sites
      previously identified by autoradiography. Thus, the highest levels of
      immunostaining were observed in the islands of Calleja, diagonal band of Broca,
      magnocellular preoptic nucleus, pre- and parasubiculum, suprachiasmatic nucleus,
      anterodorsal nucleus of the thalamus, substantia nigra, ventral tegmental area,
      pontine nuclei and dorsal motor nucleus of the vagus, all of which had previously
      been documented to contain high densities of neurotensin binding sites. There
      were, however, a number of regions reportedly endowed with neurotensin binding
      sites, including the central amygdaloid nucleus, periaqueductal gray, outer layer
      of the superior colliculus and dorsal tegmental nucleus, which showed no or
      divergent patterns of immunostaining, suggesting that they might be expressing a
      molecularly distinct form of the receptor. At the cellular level, neurotensin
      receptor immunoreactivity was predominantly associated with perikarya and
      dendrites in some regions (e.g., in the basal forebrain, ventral midbrain, pons
      and rostral medulla) and with axons and axon terminals in others (e.g., in the
      lateral septum, bed nucleus of the stria terminalis, neostriatum, paraventricular
      nucleus of the thalamus and nucleus of the solitary tract). These data indicate
      that neurotensin may act both post- and presynaptically in the central nervous
      system and confirm that some of its effects are exerted on projection neurons.
      There were also areas, such as the cerebral cortex, nucleus accumbens and para-
      and periventricular nucleus of the hypothalamus, which contained both
      immunoreactive perikarya/dendrites and axon terminals, consistent with either a
      joint association of the receptor with afferent and efferent elements or its
      presence on interneurons. Taken together, these results also suggest that the
      neurotensin high affinity receptor protein is associated with a neuronal
      population that is more extensive than originally surmised from in situ
      hybridization studies.

PMID- 8876465
TI  - Efferent pathways of the nucleus of the optic tract in monkey and their role in
      eye movements.
AB  - To clarify the role of the pretectal nucleus of the optic tract (NOT) in ocular
      following, we traced NOT efferents with tritiated leucine in the monkey and
      identified the cell groups they targeted. Strong local projections from the NOT
      were demonstrated to the superior colliculus and the dorsal terminal nucleus
      bilaterally and to the contralateral NOT. The contralateral oculomotor complex,
      including motoneurons (C-group) and subdivisions of the Edinger-Westphal complex,
      including motoneurons (C-group) and subdivisions of the Edinger-Westphal complex,
      also received inputs. NOT efferents terminated in all accessory optic nuclei
      (AON) ipsilaterally; contralateral AON projections arose from the pretectal
      olivary nucleus embedded in the NOT. Descending pathways contacted precerebellar
      nuclei: the dorsolateral and dorsomedial pontine nuclei, the nucleus reticularis
      tegmenti pontis, and the inferior olive. Direct projections from NOT to the
      ipsilateral nucleus prepositus hypoglossi (ppH) appeared to be weak, but
      retrograde tracer injections into rostral ppH verified this projection;
      furthermore, the injections demonstrated that AON efferents also enter this area.
      Efferents from the NOT also targeted ascending reticular networks from the
      pedunculopontine tegmental nucleus and the locus coeruleus. Rostrally, NOT
      projections included the magnocellular layers of the lateral geniculate nucleus
      (lgn); the pregeniculate, peripeduncular, and thalamic reticular nuclei; and the
      pulvinar, the zona incerta, the mesencephalic reticular formation, the
      intralaminar thalamic nuclei, and the hypothalamus. The NOT could generate
      optokinetic nystagmus through projections to the AON, the ppH, and the
      precerebellar nuclei. However, NOT also projects to structures controlling
      saccades, ocular pursuit, the near response, lgn motion sensitivity, visual
      attention, vigilance, and gain modification of the vestibulo-ocular reflex. Any
      hypothesis on the function of NOT must take into account its connectivity to all
      of these visuomotor structures.

PMID- 8876466
TI  - Estradiol increases the frequency of multiple synapse boutons in the hippocampal
      CA1 region of the adult female rat.
AB  - The effect of estradiol to increase the density of dendritic spines and
      axospinous synapses on hippocampal CA1 pyramidal cells in the adult female rat
      has been well-documented. However, presynaptic involvement in this process of
      synapse elimination and formation in the adult is unknown. To address this issue,
      we have reconstructed 410 complete presynaptic boutons through coded serial
      electron micrographs of CA1 stratum radiatum to determine the: (1) frequency of
      multiple (MSB) vs. single (SSB) synapse boutons; (2) number of synaptic contacts
      per MSB; (3) bouton volume and surface area; and (4) types of spines in synaptic
      contact with MSBs and SSBs in ovariectomized, estradiol-treated animals (OVX + E)
      versus ovariectomized oil-treated controls (OVX + O). Quantitative analysis of
      this tissue revealed that, in OVX + E animals, 45.0% of presynaptic boutons form
      multiple synaptic contacts with dendritic spines compared to 27.3% in controls (P
      < 0.01); the average number of synapses per dendritic spines compared to 27.3% in
      controls (P < 0.01); the average number of synapses per MSB was 2.7 in OVX + E
      animals compared to 2.3 in controls (P < 0.05). This represents a 25.5% increase
      in the number of synapses formed by a given number of presynaptic boutons in
      estradiol-treated animals (P < 0.01) which largely accounts for the previously
      observed estradiol-induced increase in axospinous synapse density. There was no
      treatment effect on bouton size; however, because MSBs are larger than SSBs, the
      increased frequency of MSBs in estradiol-treated tissue results in a trend toward
      an estradiol-induced increase in average bouton size. Additionally, MSBS were
      found to be more irregular in shape, i.e., significantly less spherical, than
      SSBs. Our results indicate that estradiol-induced dendritic spines form synapses
      primarily with preexisting boutons in stratum radiatum and that these boutons
      enlarge and change shape as they accommodate new synapses. Such findings suggest
      a relatively active role for dendrites in the process of adult synapse formation.

PMID- 8876467
TI  - Glial cells stabilize axonal protoglomeruli in the developing olfactory lobe of
      the moth Manduca sexta.
AB  - Odor information is processed in spherical structures called glomeruli, which in
      all animals with differentiated olfactory systems are sites of densely spaced
      synaptic contacts between olfactory sensory axons and target central nervous
      system (CNS) neurons. Glomerulus development in the antennal (olfactory) lobe of
      the moth brain, which is initiated by the arrival of antennal receptor axons,
      requires interaction among three elements: glial cells, receptor axons, and their
      targets, the antennal-lobe neurons. Receptor axons form an array of
      protoglomeruli that become surrounded by glia and serve as a template for mature
      glomeruli. Previous experiments showed that when the number of glial cells is
      sharply reduced during development either by irradiation or by an anti-mitotic
      agent, receptor axons form protoglomeruli, but in the mature lobes, glomeruli are
      absent and central neurons lack the characteristic glomerular tufting of their
      arbors. The current investigation was conducted to determine which cellular
      events in the process of glomerulus formation are disrupted by severe reduction
      in glial-cell number. The branching patterns of receptor axons and antennal-lobe
      neurons were examined in animals that had been irradiated to produce glia
      deficient antennal lobes at stages during which glomeruli normally would develop.
      We found that the receptor axons did form protoglomeruli, but that the
      protoglomeruli quickly disintegrated in glia-deficient antennal lobes; the
      receptor axons branched diffusely, except where several neighboring glia survived
      irradiation and together formed a wall of processes that appeared to block the
      passage of neuronal processes. Multi-glomerular antennal-lobe neurons never
      developed tufted arbors even at early stages. These results suggest that
      maintenance of protoglomeruli depends on the border of glia that forms around
      each protoglomerulus and that the subsequent tufting of antennal-lobe neurons
      depends on maintenance of the protoglomerular template during the period of
      dendritic growth.

PMID- 8876468
TI  - Differential localization of putative amino acid receptors in taste buds of the
      channel catfish, Ictalurus punctatus.
AB  - The taste system of catfish, having distinct taste receptor sites for L-alanine
      and L-arginine, is highly sensitive to amino acids. A previously described
      monoclonal antibody (G-10), which inhibits L-alanine binding to a partial
      membrane fraction (P2) derived from catfish (Ictalurus punctatus) taste
      epithelium, was found in Western blots to recognize a single band, at apparent MW
      of 113,000 D. This MW differs from the apparent MW for the presumed arginine
      receptor identified previously by PHA-E lectin affinity. In order to test whether
      PHA-E lectin actually reacts with the arginine-receptor, reconstituted membrane
      proteins partially purified by PHA-E affinity were used in artificial lipid
      bilayers. These reconstituted channels exhibited L-arginine-activated activity
      similar to that found in taste cell membranes. Accordingly, we utilized the PHA-E
      lectin and G-10 antibody as probes to differentially localize the L-alanine and L
      arginine binding sites on the apical surface of catfish taste buds. Each probe
      labels numerous, small (0.5-1.0 micron) patches within the taste pore of each
      taste bud. This observation suggests that each bud is not tuned to a single taste
      substance, but contains putative receptor sites for both L-arginine and L
      alanine. Further, analysis of double-labeled tissue reveals that the PHA-E and G
      10 sites tend to be separate within each taste pore. These findings imply that in
      catfish, individual taste cells preferentially express receptors to either L
      arginine or L-alanine. In addition, PHA-E binds to the apices of solitary
      chemoreceptor cells in the epithelium, indicating that this independent
      chemoreceptor system may utilize some receptor sites similar to those in taste
      buds.

PMID- 8876469
TI  - Mitochondrial- and nuclear-encoded subunits of cytochrome oxidase in neurons:
      differences in compartmental distribution, correlation with enzyme activity, and
      regulation by neuronal activity.
AB  - Cytochrome oxidase (CO), a mitochondrial energy-generating enzyme, contains both
      mitochondrial- and nuclear-encoded subunits. In neurons, local levels of CO
      activity vary among different neuronal compartments, reflecting local demands for
      energy. The goals of the present study were to determine if compartmental
      distribution of CO subunit proteins from the two genomes was correlated with
      local CO activity, and if their expression was regulated proportionately in
      neurons. The subcellular distributions of mitochondrial-encoded CO III and
      nuclear-encoded CO Vb proteins were quantitatively analyzed in mouse cerebellar
      sections subjected to postembedding immunocytochemistry. Local levels of subunit
      proteins were also compared to local CO activity, as revealed by CO
      cytochemistry. In order to study the regulation of subunit protein expression, we
      assessed changes in immunoreactivity of the two CO subunits as well as changes in
      CO activity in mouse superior colliculus after 1 to 7 days of monocular
      enucleation. We found that immunoreaction product for both CO III and CO Vb
      existed almost exclusively in mitochondria, but their compartmental distributions
      were different. CO III was nonhomogeneously distributed among different neuronal
      compartments, where its local level was positively correlated with that of CO
      activity. In contrast, the subcellular distribution of CO Vb was relatively
      uniform and did not bear a direct relationship with that of CO activity.
      Moreover, the two subunit proteins were disproportionately regulated by neuronal
      activity. CO III and CO activity exhibited parallel decreases after the
      deprivation of afferent input, and their changes were earlier and to a greater
      degree than that of CO Vb proteins. Thus, the present findings indicate that the
      local expression and/or distribution of CO subunit proteins from the two genomes
      may involve different regulatory mechanisms in neurons. Our data also suggest
      that the activity-dependent regulation of mitochondrial-encoded CO subunits is
      likely to play a major role in controlling the local levels of CO content and its
      activity.

PMID- 8876470
TI  - Elevated systolic blood pressure: increased cardiovascular risk and rationale for
      treatment.

PMID- 8876471
TI  - Gender considerations in hypertension pathophysiology and treatment.
AB  - Cardiovascular disease is the leading cause of death among women, yet clinical
      trials have not evaluated specific treatment strategies for women. Recently,
      there has been an expansion of scientific literature exploring differences
      between women and men with hypertension and cardiovascular disease. The
      cardioprotective effects of estrogen have been well demonstrated, and the loss of
      endogenous estrogens with aging contributes to the rapid increase in the
      incidence of coronary artery disease after menopause. Many of the adverse effects
      of estrogen deficiency are reversible with estrogen replacement. Estrogen
      improves lipoprotein profiles, has vasodilatory effects on the endothelium, and
      inhibits vascular smooth muscle cell growth and constriction. These effects
      likely all contribute to the reduction in coronary artery disease in the presence
      of estrogen, and the clinical benefits are not attenuated by concurrent
      progestins. There are gender-specific differences in the epidemiology of
      hypertension and coronary artery disease, as well as differences in the
      pathophysiology and clinical manifestations of disease. Given important
      experimental interactions between estrogens and the major classes of
      antihypertensive agents, as well as secondary benefits such as a possible
      reduction in bone loss with certain agents, a gender-specific approach to
      hypertension appears to be warranted. Future clinical trials will need to address
      gender-specific differences in treatment approaches.

PMID- 8876472
TI  - The impact of ethnicity on response to antihypertensive therapy.
AB  - The aim of this review is to assess the prevalence of complications and responses
      to various antihypertensive drug therapies in ethnic minority groups in the
      United States. In some instances, these comments are extended to responses of
      citizens in their countries of origin. The incidence of hypertension, mortality
      from hypertensive heart disease, stroke, and hypertensive renal disease are
      higher in African Americans. Although some Hispanic Americans have a lesser risk
      for hypertension, they have a greater risk for other risk factors such as
      diabetes and dyslipidemia. There is a similar association between income and
      mortality for both African Americans and Hispanic Americans. When compared to
      European Americans and other ethnic minorities, African Americans respond less
      favorably to beta blockers and angiotensin-converting enzyme (ACE) inhibitors.
      Nevertheless, the observed response in African Americans to ACE inhibitors and
      beta blockers is clinically significant. The available literature indicates that
      Asian American responses to calcium antagonists seem to be more favorable than
      responses to ACE inhibitors and equivalent to their responses to diuretic and
      beta blocker therapy. Although there are few published studies of drug efficacy
      in Hispanic Americans, there appears to be no hierarchy in response to the
      various antihypertensive drug classes. Ethnicity is not an accurate criterion for
      predicting poor response to any class of antihypertensive therapy. Thus, there is
      little justification to use racial profiling as a criterion for the avoidance of
      selected drug classes because of presumed lack of efficacy. Observed differences
      in the incidence of hypertension and its poor outcomes have led some
      investigators to postulate that the etiology of hypertension in ethnic minority
      groups is intrinsically different from whites. Awareness of racial differences in
      hypertension outcomes evolved in the United States within a historical context
      that does not fully appreciate that race is often a surrogate for many social and
      economic factors that influence health status and healthcare delivery. Poor
      outcomes in ethnic minority groups occur in many diseases, not only hypertension.
      The goal of ethnicity-related research should be to describe the diversity of
      disease expression in humans and to target at-risk groups for prevention and
      early intervention. The use of racial descriptors to explain genetic differences
      in ethnic groups should take a lesser priority.

PMID- 8876473
TI  - Therapeutic challenges in the obese diabetic patient with hypertension.
AB  - Obesity, diabetes mellitus, and hypertension are common and interrelated medical
      problems in Westernized, industrialized societies. These medical conditions are
      associated with an increased risk of cardiovascular disease and are more
      prevalent among minorities, such as African-American and Hispanic populations.
      The associated cardiovascular risks of these problems are more thoroughly
      addressed in another review in this supplement. Obesity markedly enhances the
      development of type II diabetes. Moreover, it enhances the cardiovascular risk
      associated with other risk factors, such as hypertension and dyslipidemia. Weight
      reduction in association with an aerobic exercise program improves metabolic
      abnormalities and reduces blood pressure in individuals with diabetes and
      hypertension. Frequently, however, pharmacologic treatment is required to lower
      blood pressure. Individual therapy with an angiotensin-converting enzyme (ACE)
      inhibitor is preferred initially in these individuals, with the addition of
      either a low dose diuretic or a nondihydropyridine calcium antagonist if
      additional blood pressure reduction is required. These additive agents are
      recommended, since each has been shown individually to reduce cardiovascular
      morbidity and to preserve renal function among diabetic patients. Other issues,
      such as aggressive therapy of lipids and adequate glycemic control, are also
      important strategies for reducing cardiovascular and renal morbidity and
      mortality in this very high-risk population.

PMID- 8876474
TI  - The evolution of low-dose diuretic therapy: the lessons from clinical trials.
AB  - Safe and effective antihypertensive therapy became available in the 1950s with
      the introduction of thiazide diuretics. Prior to that time, we did have agents
      that lowered blood pressure but they often needed to be given parenterally and
      were too poorly tolerated to be used for the treatment of any but those with life
      threatening elevations of blood pressure. When thiazide diuretics-first
      chlorothiazide and then hydrochlorothiazide-became available, it was possible to
      lower blood pressure in most hypertensives and assess whether that reduction
      would lead to a reduction in cardiovascular morbidity and mortality. The results
      of 17 large trials have now made it clear that antihypertensive therapy with
      regimens based on diuretics and beta blockers reduces cardiovascular events and
      saves lives. When first introduced, thiazide diuretics were prescribed at doses
      we now know are excessively high (100-200 mg of hydrochlorothiazide/day), and we
      have learned that much lower doses, even as little as 12.5 mg of
      hydrochlorothiazide, are effective. These lower doses will reduce blood pressure
      and do so with considerably less in the way of metabolic effects. This article
      will trace the development of antihypertensive therapy and review how data from
      clinical trials have influenced the recommendations of the Joint National
      Committees on the Detection, Evaluation and Treatment of Hypertension.

PMID- 8876475
TI  - Evidence for the efficacy of low-dose diuretic monotherapy.
AB  - Diuretic monotherapy has been recommended by the fifth report of the Joint
      National Committee on Detection, Evaluation and Treatment of High Blood Pressure
      (JNC-V) as a preferred initial treatment for hypertension. Thiazide diuretics are
      commonly used to treat hypertension because of their demonstrated efficacy,
      favorable safety profile, low acquisition cost, and their proven ability to
      reduce blood pressure-related morbidity and mortality. Once-daily low-dose
      hydrochlorothiazide (12.5 mg/ day) or chlorthalidone (15 mg/day) effectively
      reduces blood pressure in patients with stage 1 or stage 2 hypertension in
      comparison with placebo. Blood pressure reductions with low-dose
      hydrochlorothiazide and chlorthalidone are comparable to that achieved with
      higher doses (25 and 50 mg/day). Additional blood pressure reductions can be
      attained with concomitant use of once-daily low-dose hydrochlorothiazide or
      chlorthalidone with an angiotensin-converting enzyme (ACE) inhibitor, a beta
      blocker, or a calcium antagonist. Once-daily low-dose hydrochlorothiazide
      provides clinically meaningful blood pressure lowering while minimizing adverse
      effects, such as electrolyte disturbances, cholesterol elevations, and increases
      in serum uric acid levels.

PMID- 8876476
TI  - Combination therapy with diuretics: an evolution of understanding.
AB  - One of the current recommendations for the treatment of hypertension is a stepped
      care approach in which a second drug is added to a first-line agent when adequate
      blood pressure control has not been achieved. It has been well demonstrated in
      multiple studies that the response rate to any single class of antihypertensive
      agent, given as monotherapy, is approximately 45-55%. Thus, in approximately half
      of the hypertensive population, a second drug will be required. This is not
      surprising, since it is now well recognized that hypertension is a multifaceted
      disease process. The use of combination therapy with low-dose diuretics (< 25mg
      hydrochlorothiazide [HCTZ] or its equivalent) has become a very attractive
      alternative choice to first-line therapy. The data from clinical trials clearly
      demonstrate that 6.25 mg or 12.5 mg HCTZ has an additive or synergistic effect on
      blood-pressure reduction when used in combination with most drugs. At low doses,
      the side-effect profile with diuretics is similar to placebo. Furthermore,
      metabolic side effects are significantly reduced when diuretics are used in low
      doses. The use of low-dose diuretics in combination with other first-line agents
      significantly enhances blood-pressure control and reduces the likelihood of
      adverse events and alteration in carbohydrate, lipid, and electrolyte metabolism.
      Thus, combination therapy with low-dose diuretics provides an attractive
      alternative approach to first-line treatment of essential hypertension.

PMID- 8876477
TI  - Metabolic manifestations of low-dose diuretics.
AB  - Hypertension has been defined and treated as a disease of abnormal systolic and
      diastolic blood pressure. Recent data have, however, demonstrated that effective
      blood-pressure control has not resulted in the expected decrease in coronary
      artery disease. These findings are probably a result of hypertension being a
      complex inherited syndrome of cardiovascular risk factors, all of which are
      genetically linked and all of which contribute to the development of
      cardiovascular disease in these patients. Included in the hypertension syndrome
      are abnormalities of lipid profile, insulin resistance, changes in renal
      function, left ventricular hypertrophy and reduced arterial compliance. In many
      patients, high blood pressure is a late manifestation of this disease process.
      Since all cardiovascular risk factors contribute to heart disease in these
      patients, they should all be considered in the management of this disease
      process. Diuretics and beta blockers, when used at high doses, negatively impact
      lipid metabolism and insulin sensitivity, while angiotensin converting enzyme
      (ACE) inhibitors and calcium antagonists tend to have a neutral effect on these
      metabolic risk factors. These findings have resulted in decreased use of
      diuretics and beta blockers in favor of newer agents such as ACE inhibitors and
      calcium antagonists. However, recent data have demonstrated that when used at low
      doses (6.25 or 12.5 mg of hydrochlorothiazide), diuretics lack significant
      metabolic side effects while bringing about significant reductions in blood
      pressure. Thus, at these doses, hydrochlorothiazide is a useful drug in the
      treatment of hypertension, both as monotherapy and in combination therapy.

PMID- 8876478
TI  - Tolerability, safety, and quality of life and hypertensive therapy: the case for
      low-dose diuretics.
AB  - The safety and tolerability of antihypertensive therapies are an important
      clinical concern, because the demonstrated benefits of successful blood pressure
      lowering depend on long-term compliance with pharmacologic treatments. Thiazide
      diuretics and beta blockers have been specifically recommended as preferred
      initial drug therapy by the Fifth Joint National Committee on Detection,
      Evaluation, and Treatment of High Blood Pressure (JNC-V), unless their use is
      contraindicated by concomitant disease, there is intolerance to these agents, or
      there is a specific indication for another drug class. These recommendations are
      a result of the lengthy clinical experience with these drugs and the results of
      long-term clinical trials that have demonstrated significant reductions in
      cardiovascular morbidity and mortality. However, data from these same clinical
      studies have also shown that diuretics (and beta blockers) can cause
      abnormalities in carbohydrate, electrolyte, and lipid metabolism and also may
      influence quality of life. The safety of diuretics was evaluated with regard to
      effects on carbohydrate, electrolyte, and lipid metabolism by seeking references
      from a MEDLINE search of documents published from 1966 to 1994 based on the
      search terms "hypertension," "human," and "hydrochlorothiazide" (HCTZ) dosed in a
      range of 12.5-25 mg daily. Two long-term clinical trials using low-dose (12.5-15
      mg/day) chlorthalidone-the Systolic Hypertension in the Elderly Program (SHEP)
      and the Treatment of Mild Hypertension Study (TOMHS)-were also included. During
      the course of treatment with HCTZ in these studies, serum potassium was reduced
      and uric acid was increased in a dose-dependent manner. Although low doses of
      HCTZ elevated serum glucose, cholesterol, and triglycerides, the magnitude of
      effect was small in most cases and was probably of no clinical significance.
      Other laboratory parameters were not adversely affected, and subjective reporting
      of clinical adverse events was generally lower with low-dose HCTZ than with
      placebo or standard HCTZ dosing. The literature on the effects of low-dose
      diuretic therapy on quality of life is not large, although the results from the
      SHEP and TOMHS studies support the concept that diuretics either do not interfere
      with, or may actually improve, quality of life in hypertensive patients. Low-dose
      thiazide treatment is a well-tolerated, excellent first-line choice for
      hypertensive patients, especially older patients. However, diuretics should
      probably be avoided, whenever possible, in patients with preexisting diabetes,
      gout, and in men with erectile dysfunction.

PMID- 8876479
TI  - Comment on the fundamental orthodontic principles.

PMID- 8876480
TI  - Change and integrate--the time is now.

PMID- 8876481
TI  - The business of orthodontics.

PMID- 8876482
TI  - The inclined biteplane--a useful tool.
AB  - A technique is described to help maintain overjet and overbite reduction achieved
      with a functional appliances, while waiting to proceed with definitive treatment
      or for use after a definitive course of fixed appliance therapy to help maintain
      the achieved result.

PMID- 8876483
TI  - Orthodontic-surgical correction of a Class II, Division 2 malocclusion.
AB  - The incorporation of the total subapical osteotomy as an alternative surgical
      technique to augment standard bilateral sagittal split osteotomy in facilitating
      establishment of the profile objectives in the surgical-orthodontic treatment of
      a patient with skeletal sagittal discrepancy, is presented in this case report.
      Esthetic considerations, as well as risks involved in this type of a combined
      surgical approach, are also discussed.

PMID- 8876484
TI  - Resolution of mandibular arch crowding in growing patients with Class I
      malocclusions treated nonextraction.
AB  - The purpose of this study was to determine the manner in which mandibular arch
      crowding was resolved in Class I growing patients who were treated nonextraction.
      A retrospective study was completed with 30 patients from a postgraduate
      orthodontic clinic, treated with a variety of treatment modalities. Eight study
      models and six cephalometric parameters were examined before treatment and at the
      end of active treatment (posttreatment). The results showed that statistically
      significant increases in arch width occurred at the canine (0.9 mm), first
      premolar (1.6 mm), second premolar (1.8 mm), and first molar (1.2 mm). The
      incisors were advanced an average of 2.1 mm and proclined 6.1 degrees. The molars
      showed no anteroposterior movement. Arch perimeter increased 2.3 mm and arch
      depth increased 1.6 mm. Multiple linear regression analysis revealed that 52% of
      the variance in crowding resolution was accounted for by an increase in arch
      perimeter. It was concluded that the resolution of crowding, in this group of
      patients with Class I malocclusions, was achieved by generalized expansion of the
      buccal segments, along with advancement of the lower incisors. In some cases,
      these changes may be consistent with treatment objectives; in others, they may be
      undesirable. It is therefore important for practitioners to carefully evaluate
      treatment outcome irrespective of the treatment modality, to determine whether
      treatment objectives are being met.

PMID- 8876485
TI  - Three-dimensional dental cast analyzing system using laser scanning.
AB  - The purpose of this article is to introduce the outline of our newly developed
      three-dimensional dental cast analyzing system with laser scanning, and its
      preliminary clinical applications. The system is composed of a measuring device
      with a slit-ray laser projector and two sets of coupled charged devised video
      cameras, an image processing unit, a 16-bit personal computer as a controller,
      and an engineering workstation as a post processor. The dental cast is projected
      and scanned with a slit-ray laser beam. The raster coordinates of the target are
      determined with an image processor. Triangulation is applied to determine the
      location of each point. Generation of three-dimensional graphics of the dental
      cast takes approximately 40 minutes. About 90,000 sets of X, Y, Z coordinates are
      stored in the main memory of the microcomputer. The measurement error is less
      than 0.05 mm. Besides the conventional linear and angular measurements of the
      dental cast, we are also able to demonstrate the size of the palatal surface area
      and the volume of the oral cavity. The advantage of this system is that it
      facilitates the otherwise complicated and time-consuming mock surgery necessary
      for treatment planning in orthognathic surgery.

PMID- 8876486
TI  - Perceived orthodontist behaviors that predict patient satisfaction, orthodontist
      patient relationship, and patient adherence in orthodontic treatment.
AB  - Orthodontist-patient relationships have significant effects on the success of
      orthodontic treatment. The purpose of this study was to evaluate the effects of
      patient-perceived orthodontist behaviors on (a) patient perceived orthodontist
      patient relationship, (b) patient satisfaction, and (c) orthodontist-evaluated
      patient adherence or compliance in orthodontic treatment. The sample consisted of
      199 orthodontic patients, 94 boys and 105 girls, ages 8 to 17 years, who were
      recruited at the beginning of orthodontic treatment by a member of the research
      team who was not involved in treating the patients. The patients were asked to
      complete standardized questionnaires in a room away from the orthodontic clinic,
      8 to 12 months into treatment. At the same time, the orthodontic resident
      treating each patient completed a standard instrument that evaluated patient
      compliance. Orthodontist behavior items such as politeness, friendliness,
      communicativeness, and empathy were evaluated by the patients. Stepwise multiple
      regression analyses (p < 0.05) showed that eight behaviors predicted perception
      of the orthodontist-patient relationship (final model R2 = 0.7930 and 0.7333) as
      well as patient satisfaction (final model R2 = 0.7952) and two behaviors
      predicted patient compliance (final model R2 = 0.0986). Of the 24 orthodontist
      behaviors, 22 were significantly correlated (p < 0.0001) with favorable
      orthodontist-patient relationship and patient satisfaction. Of the 24 behaviors,
      10 were significantly correlated (five at p < 0.01 and five at p < 0.05) with
      patient compliance. Patient-perceived orthodontist behaviors are related to and
      predict (1) patient perceived orthodontist-patient relationship, (2) patient
      satisfaction, and (3) orthodontist-evaluated patient adherence or compliance.

PMID- 8876487
TI  - Time-related bond strengths of light-cured and chemically cured bonding systems:
      an in vitro study.
AB  - The immediate bond strengths achieved with a light-cured bonding system and those
      at selected time intervals over a 24-hour period were assessed and compared with
      the bond strengths produced by a chemically cured system over a similar period.
      Mesh-backed metal orthodontic brackets were bonded with the light-cured system to
      60 teeth, and 50 teeth had similar brackets bonded with a chemically cured
      system. Shear/peel bond strengths for each were determined with the instron
      Universal testing machine (Instron Corp., Canton, Mass.) and these were compared
      statistically. The bond strengths for the chemically cured system were initially
      low, but these increased with time. The light-cured sample displayed initial bond
      strengths of sufficient magnitude to withstand the immediate application of
      orthodontic forces, and these bond strengths also increased with time. There was
      no significant difference between the bond strengths achieved by the chemically
      cured and light-cured systems at the 10-minute, 60-minute, and 24-hour intervals.

PMID- 8876488
TI  - Determination of fluoride from fluoride-releasing elastomeric ligature ties.
AB  - Unaesthetic white spot lesions or larger unsightly areas of decalcification
      around orthodontic brackets remain a significant problem during fixed appliance
      treatment. This study determined the in vitro fluoride release from 200 fluoride
      containing elastomeric ligature ties. With the potentiometric analytic method,
      the fluoride release was determined in distilled water, for 10 groups of 20
      elastomerics, representing the clinical usage in a patient. Readings were taken
      every 24 hours for 5 days and then every second week for 6 months. The data were
      analyzed with the Wilcoxon matched pairs signed ranks test. Fluor-I-Ties (Ortho
      Arch Company Inc., Hoffman Estates, III.) released significant amounts of
      fluoride compared with the control readings. The fluoride release was
      characterized by an initial burst of fluoride during the first day and second
      day, followed by a logarithmic decrease. By the end of the second week 88% of the
      total fluoride had been leached from the elastomerics, but adequate magnitudes of
      fluoride were released over the remainder of the test period to aid theoretically
      in the prevention of demineralization and enhance remineralization of enamel
      through calcium fluoride and fluorapatite formation. For optimum clinical
      benefit, Fluor-I-Ties should be replaced monthly. Future prospective longitudinal
      clinical studies are indicated.

PMID- 8876489
TI  - Ceramic bracket debonding with the carbon dioxide laser.
AB  - The conventional removal of ceramic brackets can be complicated by bracket
      fracture or enamel loss. To ease this ceramic bracket removal, lasers have been
      previously investigated for thermally softening thermally the bonding resin. This
      conversion of laser light to heat can also threaten the vitality of the debonded
      teeth. Pilot studies and computer modeling suggest that for commonly used
      polycrystalline brackets debonded with the carbon dioxide laser, some form of
      mechanical assistance is needed during the lasing process to keep the intrapulpal
      temperature below the 5.5 degrees C safety threshold. One type of polycrystalline
      bracket was bonded to lower anterior bovine incisor teeth with one type of resin
      adhesive. A ceramic bracket debonding plier was modified to accommodate a laser
      waveguide so that a tensile debonding force could be applied simultaneously
      during lasing. A control group and three experimental groups were tested (n =
      10). The three experimental groups were debonded with the carbon dioxide laser at
      20 W and a static tensile force of 3 pounds, 1.5 pounds, or 0.75 pounds. The
      length of lasing time for the static force to remove the bracket was measured
      along with the increase in intrapulpal temperature. The mean debonding times and
      mean increases in intrapulpal temperature for each group were: 3 pound group,
      1.64 seconds and 1.80 degrees C; 1.5 pound group, 1.83 seconds and 3.01 degrees
      C; and 0.75 pound group, 3.42 seconds and 4.47 degrees C.

PMID- 8876490
TI  - Masseter muscle activity during the whole day in young adults.
AB  - This study was conducted to evaluate the biting function during the entire day in
      young adults by measuring the masseter muscle activity with a 24-hour
      electromyography (EMG) system. With this system, the masseter muscle activity for
      24 hours was recorded in 20 male and 10 female young adult subjects with
      acceptable occlusion. For the male subjects, means of the number and total
      duration of bursts over level 2, which is one-fourth of the maximum discharge
      voltage during maximum clenching, were 1938 times and 357 seconds. For the female
      subjects, the values were 2356 times and 419 seconds. A large percentage of such
      high amplitude bursts as level 3 or 4 was observed during meals in both groups.
      These results indicated that most of the strong bursts of the masseter muscle
      appeared only during meals and a number of low amplitude bursts were observed
      during the entire day, although masseter muscle activity during the entire day in
      young adults was less than expected. It is anticipated that the nature of
      masticatory muscle activity revealed in this study might provide valuable
      information about the association between the biting function and the
      craniofacial structure or malocclusion.

PMID- 8876491
TI  - Interleukin-1 beta and tumor necrosis factor-alpha production by human monocytes
      cultured with L-thyroxine and thyrocalcitonin: relation to severe root
      shortening.
AB  - The objectives of this study were to determine whether L-thyroxine (T4) and
      thyrocalcitonin (TCA) influence monocyte production of interleukin-1 beta (IL-1
      beta) and tumor necrosis factor-alpha (TNF-alpha) and to examine IL-1 beta and
      TNF-alpha production in monocytes from a group of orthodontic patients with
      severe root shortening. Human monocytes were incubated with varying
      concentrations of T4 and TCA for 24 hours, and IL-1 beta and TNF-alpha levels
      were measured by ELISA. At a concentration of 0.1 microgram/ml, T4 and TCA
      induced significantly more IL-1 beta than untreated controls, and T4 induced more
      IL-1 beta than TCA. Neither hormone induced significant TNF-alpha release,
      conversely, TCA had an inhibitory effect on unstimulated monocyte release of TNF
      alpha. TCA was also shown to inhibit, but not reverse, the activational effect of
      lipopolysaccharide on monocyte TNF-alpha release. T4 and TCA concentrations as
      low as 0.1 pg/ml caused monocytes to release significant amounts of IL-1 beta.
      The highest concentration of T4 tested (1.0 microgram/ml) induced significantly
      less IL-1 beta production than lower concentrations. T4- and TCA-treated
      monocytes bound more labeled IL-1 beta than untreated controls, which suggests
      that these hormones increase IL-1 receptor expression. There was a wide range of
      unstimulated and stimulated IL-1 beta and TNF-alpha production by root resorption
      subject monocytes with no significant differences between resorption and
      nonresorption group means. This data suggest that patient monocytes did not
      differ from control monocytes in regard to these cytokine parameters, and
      therefore in vitro IL-1 beta and TNF-alpha levels could not distinguish
      resorption subjects.

PMID- 8876492
TI  - Application of a classical model of competitive business strategy to orthodontic
      practice.
AB  - This study explored how market forces might affect the business aspects of
      orthodontic practices; in particular, profitability. The forces identified were
      (1) intensity of rivalry, (2) threat of new entrants, and (3) bargaining power of
      buyers and suppliers. A mail survey instrument was used to collect the data.
      Results showed that more than half the surveyed practices show an increase in new
      case starts despite weak economic conditions. Although satellite offices and
      marketing increase the overhead, they do not add to net profit. New entrants are
      a threat to existing practices, as are the substitute discretionary spending by
      the consumer. Interestingly, while some orthodontic practices have joined the
      managed care programs, a majority of them realize neither increased patient load
      nor profit. Our data seem to indicate that orthodontic practices have not been
      successful in "cost containment" with their marketing, number of employees,
      computerization or inventory. Collectively, the results of this study suggest
      that success in an orthodontic office is primarily dependent on the
      practitioner's personality traits, rather than rigidly applied business
      principles.

PMID- 8876493
TI  - Comparing and contrasting two orthodontic indices, the Index of Orthodontic
      Treatment need and the Dental Aesthetic Index.
AB  - This article compares and contrasts two orthodontic indices, the Index of
      Orthodontic Treatment Need (IOTN), and the Dental Aesthetic Index (DAI). Both
      contain esthetic and clinical criteria. Both accept the premise that a
      significant benefit of orthodontic treatment is improved esthetics and, by
      inference, social and psychological well-being. Both have as their goal the
      identification of children most in need of orthodontic treatment subsidized by
      public funds. The first part of this article describes the IOTN, its development,
      reliability, and validity. The second section describes the DAI, its development,
      reliability, and validity. The third part of the article compares and contrasts
      the indices. There are a number of differences between the IOTN and the DAI. In
      the IOTN, the esthetic component is a separate instrument from the dental health
      component. The unique aspect of the DAI is its linking of people's perceptions of
      esthetics with anatomic trait measurements by regression analysis to produce a
      single score obviating the need, as in the IOTN, for two separate scores that
      cannot be combined. Both components of the IOTN have only three grades, "no
      need," "borderline need," and "definite need." The IOTN cannot rank order cases
      with greater or lesser need for treatment within grades. In contrast, DAI scores
      can be rank ordered on a continuous scale and can differentiate cases within
      severity levels. With the IOTN, about a third of British schoolchildren would be
      found eligible for treatment in public programs. Providing publicly funded
      orthodontic care to as many as a third of the schoolchildren would not be
      feasible in the United States.

PMID- 8876494
TI  - Role of posterior transverse interarch discrepancy in Class II, Division 1
      malocclusion during the mixed dentition phase.
AB  - Posterior transverse interarch discrepancy (PTID), measured as the difference
      between the maxillary and mandibular intermolar widths, was investigated in a
      sample of 60 Class II, Division 1 subjects during the mixed dentition phase. Two
      main groups were detected: Class II group 1 (30 subjects) with PTID and Class II
      group 2 (30 subjects) without PTID. A sample of 30 Class I subjects in the mixed
      dentition phase was used as a control group. In Class II group 1, PTID was found
      to be due to a significantly narrower maxillary arch. The craniofacial skeletal
      features of both Class II groups and of the Class I group were assessed. The
      Class II group with PTID showed mandibular retrusion associated with a
      posteriorly displaced mandible of normal size (functional mandibular retrusion).
      The Class II group without PTID had mandibular retrusion due to a micrognathic
      mandible (anatomic mandibular retrusion). The relevance of these findings for
      treatment planning in Class II, Division 1 malocclusion in the mixed dentition
      was stressed.

PMID- 8876495
TI  - Cephalometric A point changes during and after maxillary protraction and
      expansion.
AB  - The purpose of this study was to analyze the treatment and posttreatment
      maxillary changes achieved with maxillary protraction therapy. The cephalometric
      records of 25 consecutively treated Chinese children with Class III malocclusions
      (mean age 8.4 years) were analyzed for cephalometric A point changes, which were
      then compared with an untreated, age and sex matched Class III control sample. A
      cephalometric maxillary superimposition technique was used to differentiate
      between the skeletal and the local contributions to the total A point change.
      Results showed that 6 months of maxillary protraction therapy produced a mean A
      point advancement of 2.4 mm compared with 0.2 mm in the control group. Of this
      advancement, 75% was found to be due to skeletal maxillary advancement and 25%
      was attributed to local remodeling. Significantly less downward movement of A
      point was found with treatment compared with the controls, which could be related
      to the direction of force application. No significant differences were found in
      the horizontal and the vertical movements of A point between the treatment and
      the control groups during the 12-month posttreatment period, indicating stability
      of early maxillary protraction in patients with Class III malocclusions.

PMID- 8876496
TI  - Craniofacial structure of Japanese and European-American adults with normal
      occlusions and well-balanced faces.
AB  - The purpose of this study is to compare two groups of adults from different races
      who were selected on the basis of having normal ("ideal") occlusions and well
      balanced faces. The lateral cephalometric radiographs of 54 Japanese adults (26
      men and 28 women) were compared with a sample of 125 adults (44 men and 81 women)
      of European-American ancestry. The samples were chosen by orthodontists of the
      same racial background as the sample selected. Each lateral cephalogram was
      traced and digitized, and differences between cephalometric measurements between
      groups were analyzed with completely randomized t tests. In comparison to the
      European-American sample, the Japanese sample, in general, was smaller in
      anteroposterior facial dimensions and proportionately larger in vertical facial
      dimensions. The facial axis angle was more vertical in Japanese subjects,
      indicating a more downward direction of facial development. On average, the
      subjects in the Japanese sample were more protrusive dentally, with a more acute
      nasolabial angle and a greater tendency toward bilabial protrusion. These
      differences, evident even in groups with so-called "well-balanced faces",
      indicate that fundamental variation exists in the craniofacial structure of
      Japanese and European-Americans. The results of this study support the premise
      that a single standard of facial esthetics is not appropriate for application to
      diverse racial and ethnic groups.

PMID- 8876498
TI  - The eighty/twenty rule.

PMID- 8876497
TI  - Prevalence of tooth agenesis and peg-shaped maxillary lateral incisor associated
      with palatally displaced canine (PDC) anomaly.
AB  - Fifty-eight nonsyndromic North American white orthodontic patients with palatal
      displacement of one or both maxillary canine teeth were studied for associated
      tooth agenesis and peg-shaped maxillary lateral incisors. Agenesis of permanent
      teeth was identified by x-ray film analysis. Conical crown-size reduction (peg
      shape anomaly) of the maxillary lateral incisor (l2) was determined by direct
      observation. Increases in absence of third molars and second premolars associated
      with the palatally displaced canine (PDC) anomaly were statistically very highly
      significant compared with normative data for tooth-agenesis prevalence. In
      contrast, the prevalence of l2 agenesis in the PDC sample showed no difference
      statistically compared with reference values. Reasons for this posterior site
      specific suppression of tooth formation are not clear. The l2 peg-shape anomaly
      exceeded a 10-fold elevation in expression in the PDC sample, a very highly
      significant increase from normal prevalence. The findings are consistent with a
      hypothesis that the anomalies of tooth agenesis, tooth-size reduction, and PDC
      are biologic covariables in a complex of genetically related dental disturbances.

PMID- 8876499
TI  - Orthodontic resources on the World Wide Web.

PMID- 8876500
TI  - Beyond mortality--residential placement and quality of life among children with
      mental retardation.

PMID- 8876501
TI  - Social class and asthma--distinguishing between the disease and the diagnosis.

PMID- 8876502
TI  - Comment: recent twists and turns in American Indian health care.

PMID- 8876503
TI  - Public health and primary care: a framework for proposed linkages.

PMID- 8876504
TI  - Racial discrimination and blood pressure: the CARDIA Study of young black and
      white adults.
AB  - OBJECTIVES: This study examined associations between blood pressure and self
      reported experiences of racial discrimination and responses to unfair treatment.
      METHODS: Survey data were collected in year 7 (1992/93) of the Coronary Artery
      Risk Development in Young Adults (CARDIA) study, a prospective multisite
      community-based investigation. Participants included 831 Black men, 1143 Black
      women, 1006 White men, and 1106 White women 25 to 37 years old. RESULTS: Systolic
      blood pressure among working-class Black adults reporting that they typically
      accepted unfair treatment and had experienced racial discrimination in none of
      seven situations was about 7 mm Hg higher than among those reporting that they
      challenged unfair treatment and experienced racial discrimination in one or two
      of the situations. Among professional Black adults, systolic blood pressure was 9
      to 10 mm Hg lower among those reporting that they typically challenged unfair
      treatment and had not experienced racial discrimination. Black-White differences
      in blood pressure were substantially reduced by taking into account reported
      experiences of racial discrimination and responses to unfair treatment.
      CONCLUSIONS: Research on racial/ ethnic distributions of blood pressure should
      take into account how discrimination may harm health.

PMID- 8876505
TI  - Judging hospitals by severity-adjusted mortality rates: the influence of the
      severity-adjustment method.
AB  - OBJECTIVES: This research examined whether judgments about a hospital's risk
      adjusted mortality performance are affected by the severity-adjustment method.
      METHODS: Data came from 100 acute care hospitals nationwide and 11880 adults
      admitted in 1991 for acute myocardial infarction. Ten severity measures were used
      in separate multivariable logistic models predicting in-hospital death. Observed
      to-expected death rates and z scores were calculated with each severity measure
      for each hospital. RESULTS: Unadjusted mortality rates for the 100 hospitals
      ranged from 4.8% to 26.4%. For 32 hospitals, observed mortality rates differed
      significantly from expected rates for 1 or more, but not for all 10, severity
      measures. Agreement between pairs of severity measures on whether hospitals were
      flagged as statistical mortality outliers ranged from fair to good. Severity
      measures based on medical records frequently disagreed with measures based on
      discharge abstracts. CONCLUSIONS: Although the 10 severity measures agreed about
      relative hospital performance more often than would be expected by chance,
      assessments of individual hospital mortality rates varied by different severity
      adjustment methods.

PMID- 8876506
TI  - Decreasing disability in the 21st century: the future effects of controlling six
      fatal and nonfatal conditions.
AB  - OBJECTIVES: This study assessed the effects of reducing fatal and nonfatal health
      conditions on the number of functionally limited older Americans in the coming
      decades. METHODS: Data from the 1990 census and the Longitudinal Study of Aging
      were used to project the number of functionally limited older Americans from 2001
      to 2049, assuming 1% biennial reductions in five conditions that shorten life
      expectancy (coronary artery disease, stroke, cancer, diabetes, and confusion) and
      one condition that decreases functional ability (arthritis). RESULTS: Decreasing
      the prevalence of arthritis by 1% every 2 years would lead to a much greater
      reduction in functional limitation between 2001 and 2049 (4 million person-years)
      than would decreasing any of the other conditions by the same amount. Decreases
      in two fatal conditions (cancer and coronary artery disease) would lead to
      increases in functional limitation (0.9 and 0.1 million person-years,
      respectively). CONCLUSIONS: Advances against common nonfatal disabling conditions
      would be more effective than advances against fatal conditions in blunting the
      large increase in the functionally limited older population anticipated in the
      21st century.

PMID- 8876507
TI  - Do beliefs, knowledge, and perceived norms about diet and cancer predict dietary
      change?
AB  - OBJECTIVES: We hypothesized that belief in an association between diet and
      cancer, knowledge of dietary recommendations and food composition, and perceived
      norms would predict healthful dietary changes. METHODS: Data are from a
      population-based sample of Washington State residents (n = 607). Psychosocial
      constructs measured at baseline (1989/90) were used to predict changes in dietary
      practices, fat intake, fiber intake, and weight over 3 years. RESULTS: Adults who
      strongly believed in a diet-cancer connection decreased the percentage of energy
      consumed from fat by 1.20 percentage points and increased fiber intake by 0.69 g,
      compared with decreases of 0.21 percentage points and 0.57 g among those with no
      belief (P < .05). Adults with knowledge of the National Cancer Institute fat and
      fiber goals decreased their percentage of energy from fat by 1.70 points compared
      with an increase of 0.27 points among those with little knowledge (P < .05). Food
      composition knowledge and perceived pressure to eat a healthful diet were not
      significant predictors of changes in fat intake, fiber intake, or weight.
      CONCLUSIONS: Interventions that increase the public's beliefs in diet and health
      associations and communicate diet recommendations can encourage healthful dietary
      change.

PMID- 8876508
TI  - The effects of poverty, race, and family structure on US children's health: data
      from the NHIS, 1978 through 1980 and 1989 through 1991.
AB  - OBJECTIVES: This study investigated the independent and relative effects of
      family structure, race, and poverty on the health of US children and youth under
      20 years of age at two time periods, 1978 through 1980 and 1989 through 1991.
      METHODS: Data were from the National Health Interview Surveys. Multivariate logit
      regression methods were used to analyze the effects of family structure, poverty,
      and race on children's health. RESULTS: Children in families headed by single
      mothers, Black children, and those living below 150% of the poverty index were
      much more likely to be in poor or fair health than children in two-parent
      families, White children, or those in more affluent families. Poverty had the
      strongest effect on child health in both time periods. CONCLUSIONS: The
      association between children's health and living below 150% of the poverty index
      is not explained by race or family structure. The disparity in child health by
      family income has serious consequences for both the child and society.

PMID- 8876509
TI  - Race, asthma, and persistent wheeze in Philadelphia schoolchildren.
AB  - OBJECTIVES: Many studies show asthma to be more common in Black than in White
      children. This study assessed how much of this difference remains after
      adjustment for other potentially race-associated predictors of asthma. METHODS:
      We assessed the predictors of active diagnosed asthma and persistent wheeze in
      1416 Black and White Philadelphia children aged 9 to 11 years, as reported by
      parents. RESULTS: Black race remained a significant predictor of active diagnosed
      asthma (odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.3, 4.1) but not
      of persistent wheeze (OR = 1.0; 95% CI = 0.6, 1.8). The excess risk of asthma in
      Black children was not appreciably altered by adjustment for other demographic
      and environmental factors. CONCLUSIONS: Black race is an important risk factor
      for active diagnosed asthma in these urban children, a relationship not explained
      by social factors. This finding and the lack of an association of race with
      persistent wheeze after adjustment for social factors suggest that race may be
      more important to the acquisition of an asthma diagnosis than to the prevalence
      of the symptoms.

PMID- 8876510
TI  - Factors associated with emergency department visits by children with asthma:
      implications for health education.
AB  - OBJECTIVES: This study investigated the relationship between psychosocial and
      behavioral factors and the frequency of emergency department visits for childhood
      asthma. METHODS: Data obtained from a survey of parents of 445 children who were
      being treated for asthma in the emergency room of a large urban hospital were
      examined. RESULTS: Factors associated with high emergency department use included
      the child's being of younger age, a greater number of days with symptoms of
      asthma, a higher number of asthma medicines prescribed, a prior hospitalization
      for asthma, a lower level of parental confidence in the efficacy of medicines,
      and a failure to use a criterion for deciding to seek emergency care.
      CONCLUSIONS: Younger children with asthma and children with previous
      hospitalization for asthma are at high risk for using emergency care. Families
      who use the emergency department frequently need to be further educated in the
      inflammatory nature of the disease, in the efficacy of proper use of medicine, in
      the need for ongoing care, and in criteria to distinguish those symptoms that can
      be handled at home from those requiring emergency care.

PMID- 8876511
TI  - Lead-contaminated house dust and urban children's blood lead levels.
AB  - OBJECTIVES: This study assessed the relationship between lead-contaminated house
      dust and urban children's blood lead levels. METHODS: A random-sample survey was
      used to identify and enroll 205 children, 12 to 31 months of age, who had resided
      in the same house since at least 6 months of age. Children's blood and household
      dust, water, soil, and paint were analyzed for lead, and interviews were
      conducted to ascertain risk factors for elevated blood lead (> or = 10
      micrograms/dL). RESULTS: Children's mean blood lead level was 7.7 micrograms/dL.
      In addition to dust lead loading (micrograms of lead per square foot),
      independent predictors of children's blood lead were Black race, soil lead
      levels, ingestion of soil or dirt, lead content and condition of painted
      surfaces, and water lead levels. For dust lead standards of 5 micrograms/sq ft,
      20 micrograms/sq ft, and 40 micrograms/sq ft on noncarpeted floors, the estimated
      percentages of children having blood lead levels at or above 10 micrograms/dL
      were 4%, 15%, and 20%, respectively, after adjusting for other significant
      covariates. CONCLUSIONS: Lead-contaminated house dust is a significant
      contributor to lead intake among urban children who have low-level elevations in
      blood lead. A substantial proportion of children may have blood lead levels of at
      least 10 micrograms/dL at dust lead levels considerably lower than current
      standards.

PMID- 8876512
TI  - Predictors of mortality in children with severe mental retardation: the effect of
      placement.
AB  - OBJECTIVES: This study was undertaken to assess the predictors of mortality in
      severely disabled children with mental retardation, and to compare risk-adjusted
      mortality rates for those living in institutions with rates for those living in
      the community. METHODS: Statistical analysis was performed on a set of 24,469
      person-years, derived from a population of all children with severe mental
      retardation and a fragile medical condition who are registered with the
      California Department of Developmental Services. Variables included age, several
      measures of mobility, the presence or absence of tube feeding, the level of
      retardation, and certain adaptive skills. RESULTS: Reduced mobility and the use
      of tube feeding were associated with a large increase in mortality risk. Own home
      residence and community care facilities have an estimated 25% higher risk
      adjusted odds on mortality than institutions and health facilities. CONCLUSIONS:
      The differential mortality in the placements points to a possible effect of
      quality of care. One consequence of the current trend toward
      deinstitutionalization may be an increased mortality rate in children with severe
      developmental disability.

PMID- 8876513
TI  - The recovery of Guatemalan children with mild to moderate wasting: factors
      enhancing the impact of supplementary feeding.
AB  - OBJECTIVES: The purpose of this study was to identify factors that enhance the
      recovery due to supplementary feeding in wasted children. METHODS: Recovery rates
      were obtained in mild to moderately wasted 6- to 48-month-old rural Guatemalan
      children living in four villages. Children in two villages received a high
      protein-energy supplement (supplemented children), while children in the other
      villages received a low protein-energy supplement (nonsupplemented children). The
      difference in recovery rates between the groups was the attributable benefit. The
      net supplementation amounted to 11% of the recommended energy intake and its
      associated nutrients. RESULTS: Attributable supplement benefits were achieved in
      younger children (6 to 24 months old) and increased with decreasing weight for
      length, longer duration of supplementation, and duration of diarrhea, but not
      with chronicity of wasting. CONCLUSIONS: Supplementation's effectiveness can be
      improved in similar populations by programs targeted according to these findings.

PMID- 8876514
TI  - Detecting risk drinking during pregnancy: a comparison of four screening
      questionnaires.
AB  - OBJECTIVES: This study investigated the efficacy of screening for risk drinking
      during pregnancy with two brief questionnaires, TWEAK and T-ACE. Both include an
      assessment of tolerance based on the number of drinks women report they can hold.
      METHODS: Subjects were disadvantaged African-American obstetric patients in
      Detroit, Mich. Traditional alcoholism screens (Michigan Alcohol Screening Test
      [MAST], CAGE) and the tolerance question were administered (n = 2717); TWEAK and
      T-ACE were constructed from tolerance and embedded MAST and CAGE items. In a
      separate sample (n = 1420), only the T-ACE was administered. Periconceptional
      risk drinking was the gold standard. Screen evaluations were based on receiver
      operating characteristic analyses. RESULTS: At the cutpoint of 2,
      sensitivity/specificity for embedded screens were 91/77 for TWEAK and 88/79 for T
      ACE; comparable values for T-ACE alone were 67/86. TWEAK and T-ACE screened more
      effectively than CAGE or MAST. CONCLUSIONS: Embedded versions of TWEAK and T-ACE
      were both highly sensitive to periconceptional risk drinking in this population.
      Administering T-ACE alone reduced its sensitivity; this suggests that MAST and
      CAGE administration improves its performance.

PMID- 8876515
TI  - The risk of myocardial infarction among Finnish farmers seeking medical care for
      an infection.
AB  - OBJECTIVES: This study determined whether people visiting a doctor because of
      infection had an increased risk of myocardial infarction. METHODS: For 83 case
      patients and 249 matched control patients nested in a cohort of 3172 Finnish male
      farmers, comparisons were made on the basis of visits to a doctor because of
      infection. RESULTS: Infections of the upper respiratory tract were statistically
      significantly associated with coronary artery disease. The odds ratio was 3.2
      (95% confidence interval = 1.2, 8.5) for patients visiting a doctor four or more
      times because of infection of upper respiratory tract compared with patients with
      three or fewer visits. CONCLUSION: Men in this sample with recurrent or chronic
      infections of the upper respiratory tract exhibited a pronounced risk for
      myocardial infarction.

PMID- 8876516
TI  - Preventing HIV/AIDS among high-risk urban women: the cost-effectiveness of a
      behavioral group intervention.
AB  - OBJECTIVES: A human immunodeficiency virus (HIV) intervention trial for women at
      high risk for acquired immunodeficiency syndrome and attending an urban clinic
      was reported previously. The behavioral group intervention was shown to increase
      condom use behaviors significantly. This study retrospectively assessed the
      intervention's cost-effectiveness. METHODS: Standard methods of cost and cost
      utility analysis were used. RESULTS: The intervention cost was just over $2000
      for each quality-adjusted life-year saved; this is favorable compared with other
      life-saving programs. However, the results are sensitive to changes in some model
      assumptions. CONCLUSIONS: Under most scenarios, the HIV prevention intervention
      was cost-effective.

PMID- 8876517
TI  - HIV test-seeking before and after the restriction of anonymous testing in North
      Carolina.
AB  - OBJECTIVES: This study assessed the impact on HIV test-seeking of North
      Carolina's restriction of anonymous testing to 18 of its 100 counties as of
      September 1, 1991. METHODS: Trends from 4 months prerestriction to the 16-month
      restriction period in counties retaining vs counties eliminating anonymous
      testing were compared. RESULTS: HIV testing increased throughout the state, but
      more rapidly where anonymous testing was retained than elsewhere: 64% vs 44%.
      These differences held for all sociodemographic subgroups and were most
      pronounced among adolescents and African Americans and other non-Whites.
      CONCLUSIONS: The data are consistent with a detrimental effect of elimination of
      anonymous testing, although confounding from differences in AIDS awareness or in
      repeat tests is possible.

PMID- 8876518
TI  - Alcohol and drug use, abuse, and dependence among welfare recipients.
AB  - OBJECTIVES: This paper presents national estimates of heavy drinking, drug use,
      and alcohol and drug abuse and/or dependence among recipients of selected welfare
      programs. METHODS: Data from the 1992 National Longitudinal Alcohol Epidemiologic
      Survey were analyzed. RESULTS: The percentages of welfare recipients using,
      abusing, or dependent on alcohol or drugs were relatively small and consistent
      with the general US population and those not receiving welfare benefits.
      CONCLUSIONS: Although a minority of welfare recipients have alcohol or drug
      problems, substance abuse prevention and treatment services are needed among high
      risk subgroups.

PMID- 8876519
TI  - Spina bifida and cleft lip among newborns of Norwegian women with epilepsy:
      changes related to the use of anticonvulsants.
AB  - OBJECTIVES: This study examined the connection between the use of anticonvulsants
      for epilepsy during or before pregnancy and the risk of spina bifida and cleft
      lip in newborns. METHODS: Among mothers registered from 1967 to 1992 by the
      Medical Birth Registry of Norway, 7588 who had epilepsy were identified and their
      newborns' prevalence of spina bifida and cleft lip examined. RESULTS: The odds
      ratio of spina bifida in children of mothers with epilepsy compared with other
      children increased from 1.5 in 1967 through 1980 (95% confidence interval [CI] =
      0.3, 4.5) to 4.4 in 1981 through 1992 (95% CI = 2.0, 8.5). The odds ratio of
      cleft lip, however, decreased from 3.0 before 1981 (95% CI = 1.6, 5.1) to 1.1
      after 1981 (95% CI = 0.4, 2.3). CONCLUSIONS: This shift toward more serious birth
      defects is consistent with the different teratogenic effects of newer and older
      anticonvulsants.

PMID- 8876520
TI  - Lower respiratory tract infections among Norwegian infants with siblings in day
      care.
AB  - OBJECTIVES: The purpose of this study was to assess the role of siblings in day
      care as a determinant of infants' risk of lower respiratory tract infections.
      METHODS: A total of 3238 children (86%) out of 3754 Oslo, Norway, newborns
      recruited in 1992/93 were followed for 1 year. RESULTS: In logistic regression
      analysis, the risk of infection was increased in (1) infants with one or more
      siblings compared with infants without siblings (adjusted odds ratio [OR] = 2.3;
      95% confidence interval [CI] = 1.84, 2.85) and (2) infants with one or more
      siblings in day care compared with infants with siblings not in day care
      (adjusted OR = 1.7; 95% CI = 1.21, 2.26). CONCLUSIONS: The results suggest that
      siblings in day care outside the home increase infants' risk of lower respiratory
      tract infections.

PMID- 8876521
TI  - Racial differences in Urban children's environmental exposures to lead.
AB  - OBJECTIVES: This study explored whether differences in environmental lead
      exposures explain the racial disparity in children's blood lead levels. METHODS:
      Environmental sources of lead were identified for a random sample of 172 urban
      children. RESULTS: Blood lead levels were significantly higher among Black
      children. Lead-contamination of dust was higher in Black children's homes, and
      the condition of floors and interior paint was generally poorer. White children
      were more likely to put soil in their mouths and to suck their fingers, whereas
      Black children were more likely to put their mouths on window sills and to use a
      bottle. Major contributors to blood lead were interior lead exposures for Black
      children and exterior lead exposures for White children. CONCLUSIONS: Differences
      in housing conditions and exposures to lead-contaminated house dust contribute
      strongly to the racial disparity in urban children's blood lead levels.

PMID- 8876522
TI  - The history and politics of US health care policy for American Indians and
      Alaskan Natives.
AB  - This paper traces the development of the US federal government's program to
      provide personal and public health services to American Indians and Alaska
      Natives since the 1940s. Minimal services had been provided since the mid 19th
      century through the Bureau of Indian Affairs of the Department of the Interior.
      As a result of attempts by western congressmen to weaken and destroy the bureau
      during the 1940s, responsibility for health services was placed with the US
      Public Health Service. The transfer thus created the only US national health
      program for civilians, providing virtually the full range of personal and public
      health services to a defined population at relatively low cost. Policy changes
      since the 1970s have led to an emphasis on self-determination that did not exist
      during the 1950s and 1960s. Programs administered by tribal governments tend to
      be more expensive than those provided by the Indian Health Service, but
      appropriations have not risen to meet the rising costs, nor are the appropriated
      funds distributed equitably among Indian Health Service regions. The result is
      likely to be an unequal deterioration in accessibility and quality of care.

PMID- 8876523
TI  - Measuring access to prenatal care in New York City: a telephone survey of
      prenatal clinics.

PMID- 8876524
TI  - Community health promotion via local minority youth: a model for academic medical
      centers.

PMID- 8876525
TI  - The persistence of a high maternal mortality rate in the Ivory Coast.

PMID- 8876526
TI  - Lead poisoning among US Hispanic children.

PMID- 8876527
TI  - Trends in restraint prevalence in US nursing homes, 1990 through 1994.

PMID- 8876528
TI  - The scope of the data available in the AMA's Physician Masterfile.

PMID- 8876529
TI  - State health agencies' role in a more balanced and sophisticated tobacco control
      program.

PMID- 8876530
TI  - The value of the population attributable risk percentage.

PMID- 8876531
TI  - Carbohydrate recognition by Mycoplasma pneumoniae and pathologic consequences.
AB  - Mycoplasma pneumoniae infection in the human is often followed by a transient
      autoimmune hemolytic disorder characterized by high titer autoantibodies to a
      carbohydrate antigen, the I antigen. Because the major host cell receptor for the
      Mycoplasma is the sialylated form of this antigen, it is likely that the
      immunologic disorder is initiated by the microbe-saccharide interaction. Here we
      review briefly knowledge on the autoantibodies and the structures and
      distribution of the saccharide antigens and receptors. We discuss possible
      mechanisms for the triggering of autoantibody production and consider ways in
      which perturbation of various glycoprotein carriers of the carbohydrate ligands
      may elicit a variety of pathobiologic responses. We conclude by highlighting
      ideas on further molecular dissections of the elements of the microbe-host
      interaction.

PMID- 8876532
TI  - Interplay between mycoplasma surface proteins, airway cells, and the protean
      manifestations of mycoplasma-mediated human infections.
AB  - Adherence of mycoplasmas to specific tissue surfaces is a crucial step in the
      establishment of infection. Several pathogenic mycoplasmas are flask-shaped and
      possess specialized tips that permit a highly oriented surface parasitism of host
      target cells. Mycoplasma pneumoniae, which causes primary atypical pneumonia in
      humans, requires a network of interactive adhesins and accessory proteins to
      cytadhere. The adhesins must cluster at the mycoplasma tip organelle in close
      association with cytadherence-related accessory proteins and a naplike structure,
      which together appear to comprise a primitive cytoskeleton-like system. Proline
      rich regions associated with these proteins play critical roles in the
      maintenance of the structural and functional integrity of the tip. Mycoplasma
      genitalium, originally isolated from the human urogenital tract of patients with
      nongonococcal urethritis, also colonizes airway cells along with M. pneumoniae.
      The molecular basis for cytadherence of these mycoplasmas is discussed in terms
      of the identification, cloning, and sequencing of the implicated mycoplasma
      genes, their common DNA and amino acid homologies and structural and functional
      domains, and the organizational similarities in their cytadherence-related
      operons. In addition, the multiorgan protean manifestations of mycoplasma
      infection are discussed in terms of the role that mycoplasma adhesins may play in
      molecular mimicry, postinfectious autoimmunity, and immune-mediated damage.

PMID- 8876533
TI  - Pertussis antigens that abrogate bacterial adherence and elicit immunity.
AB  - Infectious disease processes follow the initial steps of adherence of the
      organism to host tissues and subsequent colonization of the target tissues that
      can occur through specific adhesion-receptor systems. Bordetella pertussis, the
      human pathogen that causes whooping cough, has evolved a genetically controlled
      system whereby adhesins are expressed when they enter the human host. Two
      adhesins, filamentous hemagglutinin (FHA) and pertactin, mediate the adherence of
      the bacterium to eukaryotic cells through varied attachment mechanisms, including
      lectin-like binding sites that interact with sulfated sugars on cell surface
      glycoconjugates and the ARG-GLY-ASP binding sequence, which recognizes a family
      of integrins found on the cell surface. The differential expression of relevant
      receptors by various eukaryotic cells likely plays a role in the pathogenesis and
      immune response to the bacterium by the host, directing the organism to specific
      cell types and to specific tissue sites. Substantial evidence exists that the B.
      pertussis adhesins, FHA and pertactin, elicit immune responses that are
      protective in animal models for the disease, including serum antibody production
      and local immune responses in the respiratory tract following nasal
      administration of encapsulated antigens. Both of these adhesins are components of
      new acellular pertussis vaccines that have proven safe and highly effective for
      prevention of serious disease in infants.

PMID- 8876534
TI  - Genetic regulation of airway colonization by Bordetella species.
AB  - Bordetella species are respiratory pathogens that infect humans and other
      animals. A majority of the virulence factors expressed by these bacteria are
      regulated by a master control locus, BvgAS, a member of the two-component family
      of signal transduction systems. BvgAS senses environmental signals and mediates
      signal transduction by a phosphorylation cascade that leads to a biphasic
      transition between the Bvg+ and Bvg- phases. From natural host studies using
      Bordetella bronchiseptica, we have found that expression of Bvg+ phase factors,
      which include adhesins and toxins, is required for successful colonization of the
      mammalian respiratory tract. Suppression of the Bvg- phase motility phenotype is
      necessary for a successful interaction with the host. Although the Bvg- phase
      does not appear to be required in vivo, it does confer the ability to survive
      under conditions of severe nutrient deprivation. We hypothesize that the Bvg+
      phase is necessary and sufficient for respiratory tract colonization and the Bvg-
      phase is adapted for survival in environments encountered during transmission
      between hosts.

PMID- 8876535
TI  - Receptors in the Pseudomonas aeruginosa adherence to injured and repairing airway
      epithelium.
AB  - In the normal respiratory tract, the airway epithelial surface is protected from
      pathogenic bacterial colonization by the mucociliary clearance. The mucins
      present in the gel mucus layer exhibit a high diversity of carbohydrate receptors
      that allow specific bacterial recognition followed by bacterial and mucus
      elimination. As soon as the mucociliary clearance mechanism is impaired, the
      bacterial attachment to mucins in association with mucus stasis represent
      critical pathways for bacterial colonization of the airway epithelium. Several
      sources of injury may damage the epithelial integrity and induce partial or
      complete epithelial shedding, exposing cellular receptors and unmasked
      extracellular matrix (ECM) components that can be recognized by bacterial
      adhesins. Laminin and type I and IV collagens represent sites of Pseudomonas
      aeruginosa attachment to the ECM components. During airway epithelium repair
      after injury, particularly in cystic fibrosis (CF), the repairing cells exhibit
      apical receptors such as asialylated gangliosides (asialo GM1) to which P.
      aeruginosa adheres. The identification of the different receptors for P.
      aeruginosa, present either on the ECM proteins or on the apical surface of the
      remodeled airway epithelium, particularly in repairing respiratory CF epithelial
      cells, is a prerequisite to further therapeutic strategies to prevent airway
      colonization by P. aeruginosa.

PMID- 8876536
TI  - Interactions between glycoconjugates from human respiratory airways and
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa binds to different glycoconjugates in vitro. As six other
      bacteria, it binds to several glycolipids, mainly asialo GM1 and asialo GM2.
      Asialo GM1 has been reported to exist at the surface of cystic fibrosis cells.
      The binding of P. aeruginosa to asialo GM1 involves the pili, especially the C
      terminal part of pilin that recognizes the GaINAc(beta 1,4) Gal sequence of
      asialo GM1.P. aeruginosa may also bind to sialylated membrane-bound
      glycoproteins. Human salivary and respiratory mucins are also recognized by P.
      aeruginosa. Mucins represent the main components of mucus. The peptide part
      (apomucin) of this broad family of secreted glycoproteins is encoded by several
      mucin genes. The apomucins are covered by a large number of carbohydrate chains
      that can be remarkably different and represent a mosaic of sites for attachment
      of microorganisms. The binding of P. aeruginosa to mucins involves outer membrane
      proteins and mucin carbohydrate chains that are structurally different from the
      carbohydrate recognized by pillin. Airway and salivary mucins secreted by
      patients suffering from cystic fibrosis (CF) show alterations in their
      carbohydrate moiety. The increased sulfation of airway mucins seems to correspond
      to a primary defect. Other abnormalities such as increased sialylation or
      fucosylation have also been detected. The binding of P. aeruginosa to airway or
      salivary mucins is increased in CF. However, the precise link between the
      carbohydrate alterations and the increased binding of P. aeruginosa to CF mucins
      remains to be elucidated.

PMID- 8876537
TI  - Recognition of mucin by the adhesin-flagellar system of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa colonizes the mucus of patients with chronic lung diseases
      by a specific mechanism involving an adhesin-receptor system. Several adhesins
      have been implicated in the adhesion of P. aeruginosa to cells, but the identity
      of the principal adhesin(s) involved in adhesion to mucin is unknown. Mutagenesis
      studies have indicated that P. aeruginosa adhesion is under the control of the
      rpoN gene, which also regulates pilin synthesis, flagellum formation, and other
      functions. Mutagenesis of certain flagellar genes that are not controlled by
      RpoN, e.g., flif, also indicates a close relationship between adhesion and
      flagellar genes and not necessarily an independent effect of rpoN on adhesion.
      Mutants of certain early flagellar genes lead to the loss of both adhesion and
      motility, whereas mutants of certain late genes, e.g., fliC, the gene for
      flagellin, lose motility but retain adhesion. Recent studies indicate that both
      motility and adhesion are regulated by a two-component regulatory system called
      fleS-R, which in turn is controlled by another regulator in a cascade that
      involves rpoN. A fleR mutant possessing pili adheres poorly to mucins,
      definitively showing that pili do not play a major role in adhesion to mucin. It
      is unclear whether the adhesin is a flagellar protein or another protein that
      uses the flagellar export apparatus for localization or both. Finding the gene
      under control of rpoN may provide answers to these questions.

PMID- 8876538
TI  - How mutant CFTR may contribute to Pseudomonas aeruginosa infection in cystic
      fibrosis.
AB  - Patients with cystic fibrosis (CF) have a pronounced hypersusceptibility (80 to
      90%) to Pseudomonas aeruginosa infection. We hypothesized that airway epithelial
      cell ingestion of bacteria followed by cellular desquamation may protect the lung
      from infection, and epithelial cells expressing mutant forms of the cystic
      fibrosis transmembrane conductance regulator (CFTR) may be defective in this
      function. We found that transformed human airway epithelial cells homozygous for
      the delta F508 allele of CFTR were significantly defective in uptake of P.
      aeruginosa compared with the same cell line complemented with the wild-type
      allele of CFTR. Partial membrane expression of the delta F508 CFTR protein occurs
      in cells grown at 26 degrees C, and under these conditions uptake of P.
      aeruginosa occurred at levels comparable to cells with a wild-type allele of
      CFTR. Epithelial cell ingestion assays using isogenic bacterial strains differing
      in lipopolysaccharide (LPS) phenotype, along with inhibition studies, identified
      the LPS-core oligosaccharide as the bacterial ligand for epithelial cell
      invasion. Inhibition of epithelial cell ingestion of P. aeruginosa in a neonatal
      mouse lung infection model led to increased levels of bacteria in the lungs 24
      and 48 h after infection. Defective epithelial cell internalization of P.
      aeruginosa may be a critical factor in hypersusceptibility of CF patients to
      chronic lung infections.

PMID- 8876539
TI  - Differential gene expression by Pseudomonas aeruginosa during interaction with
      respiratory mucus.
AB  - Pseudomonas aeruginosa is a common respiratory tract pathogen that causes serious
      infections in patients with cystic fibrosis. A number of putative virulence
      factors have been characterized in several laboratories, and some have been
      implicated in human infections, based on criteria such as the phenotype of
      isolates from infected patients, an immune response to a particular antigenic
      factor, and the effect of a virulence factor on infectivity in an animal model.
      We have developed a series of genetic tools to study the selective regulation of
      expression of P. aeruginosa genes during interactions of the pathogen with host
      tissues. These tools are based on direct enrichment of bacteria, when a
      particular promoter is induced or repressed. We have found that interaction of
      bacteria with mucus from patients with cystic fibrosis results in marked
      induction of expression of several genes, including one that encodes a
      lipopolysaccharide biosynthetic enzyme, a gene for a protein responsible for
      uptake of the ferric pyochelin siderophore, and a new gene homologous with a
      class of iron-responsive repressors. The tools described here are useful for
      identification of induced or repressed genes in various animal models of
      infection or in controlled laboratory conditions that mimic natural infections of
      humans. Such genes might not be detectable when bacteria are cultured in
      laboratory conditions, and these tools are therefore useful for general probing
      of a bacterial genome for genes regulated during different stages of infection.

PMID- 8876540
TI  - Aspects on the interaction of Streptococcus pneumoniae and Haemophilus influenzae
      with human respiratory tract mucosa.
AB  - Haemophilus influenzae and Streptococcus pneumoniae are common causes of
      respiratory tract infections. H. influenzae attach to receptor epitopes in mucins
      and in epithelial cell membranes. Attachment is followed by an epithelial cell
      cytokine response. Secreted cytokines then initiate inflammation, upset the
      integrity of the mucosal barrier, and lead to disease. S. pneumoniae do not bind
      to mucins but attach to respiratory tract epithelial cells. Attachment is
      increased by viral infection of the epithelial cells. Unlike H. Influenzae, S.
      pneumoniae induce apoptosis in epithelial cells, thus disrupting the mucosal
      barrier. Attachment and persistence is counterbalanced by antiadhesive as well as
      bactericidal molecules in secretions such as human milk. These examples
      illustrate the balance between host defenses and microbial virulence as it has
      coevolved to maintain the health of the respiratory mucosa.

PMID- 8876541
TI  - Molecular determinants of the interaction between Haemophilus influenzae and
      human cells.
AB  - Haemophilus influenzae is a human-specific pathogen that must colonize the human
      upper respiratory tract to avoid extinction. On occasion, organisms penetrate the
      epithelial barrier and cause bacteremic disease or spread within the respiratory
      tract to produce localized disease. Attachment to host epithelium is fundamental
      to the process of colonization and to the pathogenesis of disease. Accordingly,
      H. influenzae has evolved to express a number of factors that promote interaction
      with human epithelial cells. Our current understanding of H. influenzae type b
      and nontypable H. influenzae adhesins is reviewed in this report. In addition,
      models are proposed for the interrelationship of these molecules.

PMID- 8876542
TI  - The effects of bacterial products on airway cells and their function.

PMID- 8876543
TI  - Autotoxicity of nitric oxide in airway disease.
AB  - Though nitric oxide (NO) plays a role in many normal pulmonary functions and is
      involved in inflammatory and immune responses, it also has cytopathologic
      potential if not tightly controlled. In Bordetella pertussis infection, NO
      mediates the respiratory epithelial pathology that is a hallmark of the pertussis
      syndrome. Tracheal cytotoxin (TCT) released by B. pertussis triggers the
      production of an inducible NO synthase (iNOS) within tracheal epithelial cells,
      which produce the NO ultimately responsible for their destruction. The induction
      of iNOS is most likely due to the cytokine interleukin-1, which is generated
      intracellularly in response to TCT; this cytokine, like TCT, can reproduce the
      pathology caused by B. pertussis infection. Similar epithelial destruction is
      observed in asthma, but the precise mechanism of damage remains incompletely
      defined. It is possible that NO induced by proinflammatory cytokines in the
      asthmatic respiratory epithelium plays a central role in the observed epithelial
      damage in asthma as it does in pertussis.

PMID- 8876544
TI  - Training Program Directors Committee position statement on Health Care Reform.
      American Academy of Allergy, Asthma and Immunology.

PMID- 8876545
TI  - Origin of late phase histamine release.

PMID- 8876546
TI  - A placebo- and active-controlled randomized trial of prophylactic treatment of
      seasonal allergic rhinitis with mometasone furoate aqueous nasal spray.
AB  - BACKGROUND: Topical nasal corticosteroids have become a mainstay of treatment for
      the symptoms of seasonal allergic rhinitis (SAR). It is likely that topical
      corticosteroids, by blocking an initial influx of inflammatory cells in the nasal
      mucosa induced by aeroallergens, may have a preventive effect on nasal allergy
      symptoms when administered before the pollen season. OBJECTIVE: This study was
      designed to assess the efficacy and safety of an 8-week course of mometasone
      furoate nasal spray (MFNS), 200 micrograms once daily, in the treatment of SAR
      compared with beclomethasone dipropionate aqueous nasal spray (BDP), 168
      micrograms twice daily, and placebo vehicle, when treatment is initiated before
      the anticipated onset of the ragweed season. METHODS: Three hundred forty-nine
      patients with SAR to ragweed pollen from nine centers in the Northeast and
      Midwest of the United States were randomized to one of the three intranasal study
      medications (MFNS, 200 micrograms once daily, BDP, 168 micrograms twice daily, or
      placebo vehicle), starting 4 weeks before the estimated start of the ragweed
      season. RESULTS: The proportion of "minimal symptom" days (total nasal symptom
      score < or = 2) was statistically significantly higher in both the MFNS and BDP
      groups when compared with the placebo vehicle group (p < 0.01). The two active
      treatment groups were not statistically significantly different from each other.
      MFNS and BDP displayed a similar safety profile that did not differ from placebo.
      CONCLUSIONS: This suggests that MFNS, 200 micrograms (once daily), is a useful
      therapy in the prophylactic treatment of SAR.

PMID- 8876547
TI  - Contact allergy: another occupational risk to Tetranychus urticae.
AB  - BACKGROUND: Tetranychus urticae is a phytophagous, macroscopic mite ubiquitous to
      warm climates, which causes occupational allergic symptoms in farm workers.
      OBJECTIVE: This study was designed to investigate the cause and mechanisms of an
      otherwise "undetermined" recurrent and occupational dermatitis on the hands of
      farm workers and to obtain a better diagnostic profile of the urticaria that many
      farm workers who are allergic to T. urticae experience. METHODS: Fifty-six farm
      workers with occupational cutaneous and/or respiratory symptoms and 10 healthy
      farm workers underwent in vivo and in vitro diagnostic trials by skin prick
      testing, serum-specific IgE determination, and three different types of
      epicutaneous tests. RESULTS: Four of the 10 patients with recurrent dermatitis
      had a positive IgE reaction to T. urticae, and five of the 10 had a positive
      patch test response. The percentage of positive patch test responses between
      subjects with positive T. urticae IgE and those with negative T. urticae IgE was
      similar. The diagnostic trial allowed the diagnosis of immune-mediated contact
      dermatitis in seven of the 10 patients with recurrent occupational dermatitis on
      the hands. The result of the epicutaneous open test on healthy skin with no
      history of eczema was positive in almost all patients with IgE to T. urticae and
      episodes of occupational urticaria. CONCLUSIONS: Urticaria frequently occurring
      in farm workers allergic to T. urticae is an allergic contact urticaria. T.
      urticae is also directly responsible for recurrent dermatitis, caused by a
      different immune-mediated mechanism, in farm workers.

PMID- 8876548
TI  - The isolation and characterization of a novel collagenolytic serine protease
      allergen (Der p 9) from the dust mite Dermatophagoides pteronyssinus.
AB  - BACKGROUND: Dust mites have been shown to contain a serine protease distinct from
      the previously reported trypsin and chymotrypsin. The latter enzymes have been
      shown to be allergens, but the allergenic importance of the former is unknown.
      OBJECTIVE: This study was performed to isolate and characterize the novel mite
      serine protease and determine its allergenicity. METHODS: The mite serine
      protease was isolated from feces-enriched extracts of Dermatophagoides
      pteronyssinus by ion-exchange chromatography and affinity chromatography, and its
      physicochemical properties were determined. The allergenicity of the protease was
      assessed by using the RAST. RESULTS: The protease was enzymatically similar to
      chymotrypsin and cathepsin G-like enzymes from a variety of sources and was shown
      to cleave collagen. It had a molecular mass of 23,780 d. N-terminal sequence
      analysis (18 residues) indicated homology with the mite tryptic allergen, Der p
      3, and the chymotryptic allergen, Der p 6. RAST analyses showed that the
      frequencies of reactivity to the novel allergen and to Der p 1, Der p 2, Der p 3,
      and Der p 6 were 92%, 97%, 100%, 97%, and 65%, respectively (n = 35). RAST
      inhibition studies showed some cross-reactivity between the protease and Der p 3
      but not Der p 6. CONCLUSIONS: A novel mite serine protease was isolated from D.
      pteronyssinus and found to be a major allergen. This allergen has been
      tentatively designated Der p 9.

PMID- 8876549
TI  - The safety of astemizole in pregnancy.

PMID- 8876550
TI  - Aspirin desensitization treatment of aspirin-sensitive patients with
      rhinosinusitis-asthma: long-term outcomes.
AB  - BACKGROUND: Aspirin-sensitive patients with asthma experience continuous
      inflammation of their nasal and sinus tissues, complicated by recurrent
      sinusitis, which frequently leads to asthma attacks. Systemic corticosteroid
      therapy and sinus or polyp surgery are currently required to control underlying
      rhinosinusitis, and bursts of corticosteroids are used for asthma control.
      OBJECTIVE: After aspirin desensitization therapy, objective measures of
      respiratory disease activity, linked to the need for systemic corticosteroids and
      sinus surgery, were studied to determine whether any changes occurred. METHODS:
      Sixty-five aspirin-sensitive patients with asthma underwent aspirin challenge,
      followed by aspirin desensitization and daily treatment with aspirin over 1 to 6
      years (mean, 3.1 years). Clinical outcome measurements before aspirin
      desensitization treatment and during follow-up were analyzed for the larger group
      of 65 patients and subgroups (29 patients receiving therapy for 1 to 3 years and
      36 patients receiving therapy for 3 to 6 years). RESULTS: In the larger group of
      65 patients, there were significant reductions in numbers of sinus infections per
      year (median, 6 to 2), hospitalizations for treatment of asthma per year (median,
      0.2 to 0), improvement in olfaction (median, 0 to 2), and reduction in use of
      systematic corticosteroids (mean, 10.2 to 2.5 mg) with p values less than 0.0001.
      Numbers of sinus and polyp operations per year were significantly reduced
      (median, 0.2 to 0; p = 0.004), and doses of nasal corticosteroids (in micrograms)
      were significantly reduced (mean dose, 139 to 106 micrograms, p = 0.01).
      Emergency department visits and use of inhaled corticosteroids were unchanged.
      CONCLUSIONS: The results support a role for aspirin desensitization treatment of
      aspirin-sensitive patients with rhinosinusitis-asthma.

PMID- 8876551
TI  - Paroxysmal atrial fibrillation after insect sting.

PMID- 8876552
TI  - Reduced pulmonary function in multiple food-induced, exercise-related episodes of
      anaphylaxis.

PMID- 8876553
TI  - Detection of the chemokine RANTES and endothelial adhesion molecules in nasal
      polyps.
AB  - BACKGROUND: To better understand the mechanisms of eosinophil recruitment into
      the upper airways, we examined human nasal polyps for the expression of the
      chemotactic cytokine RANTES and the endothelial adhesion molecules E-selectin and
      vascular cell adhesion molecule-1 (VCAM-1). METHODS: Routine histologic
      examination and immunostaining with antibodies to RANTES, E-selectin, and VCAM-1
      were performed on three types of tissues: nasal polyps, sinus mucosa, or
      turbinates from patients undergoing other elective procedures (S/T), and nasal
      biopsy specimens from nonallergic volunteers (NA). To further quantify the
      expression of endothelial adhesion molecules, some tissue samples were
      homogenized, and the resulting supernatants were assayed with sandwich ELISAs for
      VCAM-1 and E-selectin. RESULTS: Polyp eosinophil counts ranged from 19/mm2 to
      1818/mm2 (763 +/- 120/mm2, mean +/- SEM) and were significantly higher than those
      found in the control tissues (5 +/- 2 in S/T samples and 20 +/- 9 in NA samples,
      p < 0.002). Immunochemical staining for RANTES was observed in 11 of 14 polyps;
      intense staining for RANTES (grade 3) was observed in six of 14 polyps. None of
      nine S/T samples or five NA samples demonstrated grade 3 staining. Staining with
      anti-RANTES was largely localized to airway and glandular epithelium. There was
      no significant correlation between counts of eosinophils or the combined total of
      eosinophils plus mononuclear cells and the intensity of epithelial RANTES
      staining in all nasal tissues. Staining for VCAM-1, as well as for E-selectin,
      was detected in 11 of 14 polyps and eight of 13 control tissues. VCAM-1 detected
      by ELISA in polyp tissues (6.8 +/- 1.3 micrograms/gm) was higher than that found
      in six S/T samples (1.2 +/- 0.3 micrograms/gm, p < 0.005) and in two NA samples
      (1.8 +/- 0.02 micrograms/gm, p = 0.08). E-selectin values in polyps (1.4 +/- 0.3
      micrograms/gm) were not statistically different from those detected in six S/T
      samples (0.5 +/- 0.2 microgram/gm) or two NA samples (1.6 +/- 0.4 microgram/gm).
      Counts of eosinophils and eosinophils plus mononuclear cells displayed a strong
      correlation with VCAM-1 ELISA values (p < 0.005 and p < 0.004, respectively) but
      not with VCAM-1 staining. VCAM-1 staining correlated with EG2-positive
      eosinophils in nasal polyp tissues (p < 0.01). E-selectin staining did not
      correlate with either neutrophil or eosinophil counts. CONCLUSIONS: These studies
      demonstrate that the chemokine RANTES is produced in vivo predominantly to nasal
      epithelium. Endothelial activation, as indicated by adhesion molecule expression,
      occurs in human nasal polyp tissues and in control tissues, possibly reflecting
      the continued antigen exposure of the nasal mucosa. The correlations found in
      this study suggest that expression of VCAM-1 plays a role in the selective
      recruitment of eosinophils and mononuclear cells into nasal polyp tissues and
      that RANTES may be more important in localizing eosinophils to the epithelium.

PMID- 8876554
TI  - The threshold for immune cell reactivity to milk antigens decreases in cow's milk
      allergy with intestinal symptoms.
AB  - BACKGROUND: In cow's milk allergy (CMA) with intestinal symptoms, peripheral
      blood mononuclear cells (PBMCs) secrete tumor necrosis factor-alpha (TNF-alpha),
      altering intestinal function. However, the type of cow's milk protein (CMP) that
      triggers symptoms (intact or intestinally processed) is not known, and neither is
      the minimal amount required. METHODS: PBMCs were isolated from infants with
      active CMA or cured infants just before a new challenge and stimulated with
      intact or intestinally processed CMP. Supernatants were tested for cytokine
      content and for their ability to perturb intestinal barrier capacity, measured in
      Using chambers in HT29-19A intestinal cells. RESULTS: PBMCs from infants with
      active CMA secreted more TNF-alpha, when they were stimulated with intact rather
      than intestinally processed CMPs, and more TNF-alpha than PBMCs from cured
      infants. Accordingly, supernatants from PBMCs stimulated with intact but not
      intestinally processed CMPs significantly increased intestinal permeability. The
      CMP concentration required to trigger TNF-alpha secretion capable of altering
      intestinal function was very small in infants with active CMA (approximately 2
      micrograms/ml), but about 300 times higher in cured infants. CONCLUSION: Intact
      rather than intestinally processed proteins stimulate PBMCs to release TNF-alpha
      and alter intestinal barrier capacity. The threshold for PBMC reactivity to milk
      antigens drops considerably during active CMA with intestinal symptoms.

PMID- 8876555
TI  - Histamine release in intact human skin by monocyte chemoattractant factor-1,
      RANTES, macrophage inflammatory protein-1 alpha, stem cell factor, anti-IgE, and
      codeine as determined by an ex vivo skin microdialysis technique.
AB  - BACKGROUND: The chemokines monocyte chemoattractant factor-1, RANTES, and
      macrophage inflammatory protein-1 alpha release histamine from human basophils,
      as well as rat and mouse mast cells. The purpose of this investigation was to
      determine whether these chemokines release histamine from human skin mast cells
      in situ. METHODS: A microdialysis technique was used to measure histamine release
      in skin. First, the model was validated by using anti-IgE, codeine, and stem cell
      factor (SCF); then the histamine-releasing effects of the chemokines were
      investigated. A total of 47 skin specimens from 41 donors were investigated.
      Hollow microdialysis fibers were inserted intradermally, and each fiber was
      slowly perfused (3 microliters/min). Anti-IgE, codeine, SCF, or chemokines were
      injected intradermally above individual fibers, and dialysate was collected at 2
      minute intervals for 20 minutes. Each series of investigations comprised five to
      eight single experiments. RESULTS: Anti-IgE (4 to 4000 U/ml), codeine (0.001 to 1
      mg/ml), and SCF (5.4 x (10(-11) to 10(-8) mol/L)) released histamine in a dose
      dependent manner; maximum histamine release was 97.4, 116.3, and 9.5 pmol/20 min,
      respectively. Monocyte chemoattractant factor-1, RANTES, and macrophage
      inflammatory protein-1 alpha in concentrations of 10(-10) to 10(-6) mol/L did not
      release histamine; histamine release by 10(-6) mol/L chemokine was less than 0.2
      pmol/20 min. None of the chemokines modulated anti-IgE-induced histamine release.
      In contrast, SCF significantly potentiated anti-IgE-induced histamine release by
      33%. All chemokines, but not SCF, released histamine from human basophils.
      CONCLUSION: We conclude that the chemokines monocyte chemoattractant factor-1,
      RANTES, and macrophage inflammatory protein-1 alpha do not release histamine from
      human skin mast cells.

PMID- 8876556
TI  - Cross-reactivity between Cupressus arizonica and Cupressus sempervirens pollen
      extracts.
AB  - BACKGROUND: Cupressus arizonica and C. sempervirens, two species belonging to the
      Cupressaceae family, are recognized as an important cause of respiratory
      allergies in countries with a Mediterranean climate. OBJECTIVE: The relationship
      between pollen extracts from these two species was studied by evaluating the
      reactivity with polyclonal rabbit antisera and human IgE. METHODS: The two
      extracts were analyzed by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis. Cross-reactivity was evaluated by ELISA and immunoblotting
      inhibition experiments. RESULTS: The electrophoretic patterns of the two extracts
      are quite different, although some components display identical molecular
      weights. The immunoblotting developed with human IgE from subjects allergic to
      members of the Cupressaceae family indicated that two major IgE-reactive
      components, displaying molecular weights of about 43,000 and 36,000 d, were
      similarly detected in both extracts. Inhibition experiments showed a high degree
      of crossreactivity between the two extracts when tested with rabbit polyclonal
      antibodies against C. arizonica and C. sempervirens. When tested with human IgE
      inhibition methods, both extracts were able to reciprocally inhibit all of the
      IgE-reactive bands, although C. arizonica extract was always a better inhibitor.
      CONCLUSIONS: C. arizonica and C. sempervirens extracts are highly cross-reactive
      at the IgE level and share a number of common epitopes also identified by
      polyclonal rabbit antisera.

PMID- 8876557
TI  - Ubiquitous structures responsible for IgE cross-reactivity between tomato fruit
      and grass pollen allergens.
AB  - The simultaneous presence of IgE reactivity to tomato fruit and grass pollen
      allergens is evident in many patients with allergy and may be caused by cross
      reactivity. Using sera from polysensitized patients with a positive enzyme
      allergosorbent test (EAST) result (score > 2), we tested reactivity to both
      allergen sources. IgE reactivity against both extracts was demonstrated in eight
      serum samples, and cross-reactivity was confirmed by the EAST inhibition assay.
      The structures responsible for this cross-reactivity were identified by Western
      blotting: five of the eight sera demonstrated a 16 kd protein in both extracts,
      which was identified as profilin. Additionally, seven of the eight sera showed
      IgE binding to epitopes on carbohydrate moieties, which contained alpha 1, 3
      fucosylations. To determine the allergens of tomato fruit extract, we performed
      two-dimensional polyacrylamide gel electrophoresis blotting. We were able to
      demonstrate one highly concentrated and about 20 weaker proteins possessing
      terminal fucose residues. These are similarly found in grass pollen extracts. It
      is therefore postulated that the cross-reactivity is affected by profilins and
      similar carbohydrate determinants. If carbohydrate structures can provoke IgE
      cross-reactivity between phylogenetically distant species, such structures may
      play an important role in sensitization and mediator release. The ubiquitous
      nature of the IgE-binding determinants was studied by additional EAST inhibition
      tests with tomato allergen disks and extract from birch pollen, mugwort pollen,
      apple, and celery, leading to significant inhibitions among all these allergen
      sources. Epitopes exclusive to grass pollen and tomato have not been detected.

PMID- 8876558
TI  - Induction of allergen-specific IL-2 responsiveness of lymphocytes after
      respiratory syncytial virus infection and prediction of onset of recurrent
      wheezing and bronchial asthma.
AB  - BACKGROUND: In pediatric patients with bronchial asthma and/or atopic dermatitis,
      peripheral lymphocytes are activated if they are stimulated with the responsible
      antigen, resulting in induction of responsiveness to IL-2. Because some nursing
      infants experience recurrent wheezing after respiratory syncytial virus (RSV)
      infection, attention is being directed to progression of the disease to bronchial
      asthma. OBJECTIVE: The study was designed to elucidate the mechanism of the onset
      of allergic diseases after RSV infection. METHODS: We examined allergen-specific
      IL-2 responsiveness induced in lymphocytes in the peripheral blood of infants
      after infection by RSV. The relationship between the onset of recurrent wheezing
      and antigen-specific IL-2 responsiveness was analyzed in 25 pediatric patients
      who could be followed up for 3 years after RSV infection. RESULTS: Stimulation of
      lymphocytes with ovalbumin, alpha-casein, and mite (Dermatophagoides farinae)
      antigens induced significantly higher responsiveness to IL-2 in the RSV-infected
      infant group than in the healthy infant and disease control groups of the same
      age. There was no clear correlation between the IgE RAST scores for D. farinae,
      ovalbumin, and alpha-casein and IL-2 responsiveness. The families of RSV-infected
      infants had a high incidence of history of allergy (67%), but there was no
      significant difference in the incidence of patients with positive test results
      for IL-2 responsiveness between the groups with and without a familial history of
      allergy. The D. farinae-specific IL-2 responsiveness was significantly increased
      in the group with the symptom (16 patients) for a value of 1.64 +/- 0.13 (mean +/
      SEM) compared with the value of 1.31 +/- 0.21 in the asymptomatic group (9
      patients). The incidence of patients with positive test results for IL-2
      responsiveness was 68.8% in the symptomatic group and 44.4% in the asymptomatic
      group. Similarly, the ovalbumin-specific IL-2 responsiveness was significantly
      increased in the symptomatic group (1.63 +/- 0.17) compared with the asymptomatic
      group (1.12 +/- 0.26). The incidence of patients with positive test results was
      62.5% and 22.2%, respectively. alpha-Casein-specific IL-2 responsiveness was also
      higher in the symptomatic group than in the asymptomatic group, but the
      difference was not statistically significant. In the patient groups without RSV
      infection, on the other hand, the D. farinae-, ovalbumin-, and alpha-casein
      specific IL-2 responsiveness in the symptomatic group were all similar to that in
      the asymptomatic group; no significant increases were detected. CONCLUSION: The
      results indicated that after RSV infection, lymphocytes acquire specific
      susceptibility to D. farinae, a mite antigen, and food antigens, particularly
      ovalbumin. Hence, it is thought that positive IL-2 responsiveness specific for D.
      farinae and/or ovalbumin, detected several months after RSV infection, can be a
      prediction factor for the onset of allergic diseases, such as recurrent wheezing
      and bronchial asthma.

PMID- 8876559
TI  - Immune complexes from HIV-1+ patients contain infectious virus able to infect
      normal lymphocytes.
AB  - It has been suggested that circulating immune complexes containing HIV-1 could be
      involved in enhancement of the infection through Fc receptors. To test this
      hypothesis, immune complexes precipitated from the sera of 25 HIV-1-seropositive
      individuals, at different stages of the disease, were assayed for the presence of
      infectious virus. When added to phytohemagglutinin-activated peripheral blood
      lymphocytes, seven of 25 complexes were able to sustain a productive infection.
      This was demonstrated by release of HIV-p24 antigens in the supernatant of
      activated but not resting peripheral blood lymphocytes after several days of
      culture. Moreover, peripheral blood lymphocytes cultured with complexes from HIV
      1+ patients but not from control subject, contained integrated HIV-1 provirus in
      their DNA. These results demonstrated the presence of infectious virus in immune
      complexes from HIV-1+ patients.

PMID- 8876560
TI  - The presence of membrane-bound stem cell factor on highly immature
      nonmetachromatic mast cells in the peripheral blood of a patient with aggressive
      systemic mastocytosis.
AB  - BACKGROUND: Systemic mastocytosis is characterized by mast cell infiltration of
      bone marrow and tissues in the absence of identified circulating bone marrow
      derived progenitors. A 58-year-old man was first seen with aggressive systemic
      mastocytosis manifested by urticaria pigmentosa, hepatosplenomegaly, generalized
      bone lesions, anemia, thrombocytopenia, monoclonal gammopathy, and increased
      urine histamine levels. OBJECTIVES AND METHODS: A rapidly progressive anemia and
      thrombocytopenia dictated a splenectomy. We sought to identify the mast cell
      progenitors in the peripheral blood and to provide evidence of their maturation
      in tissues with immunohistochemical and ultrastructural analyses. RESULTS: The
      peripheral blood contained 1% to 3% nonmetachromatic mononuclear cells with
      eccentric nuclei that expressed the mast cell proteases, tryptase and
      carboxypeptidase A, along with c-kit, stem cell factor (SCF), and high-affinity
      IgE receptor (Fc epsilon RI), but not chymase. Similar mononuclear cells
      colocalized in the spleen and lymph nodes with mature, metachromatic mast cells
      that expressed tryptase, chymase, carboxypeptidase A, c-kit, SCF, and Fc epsilon
      RI. Electron microscopy disclosed, at each site, a mature mast cell population
      with electron-dense, scroll-poor granules. CONCLUSIONS: The peripheral blood of a
      patient with aggressive systemic mastocytosis contained immature mononuclear
      cells of the mast cell lineage that express c-kit, SCF, tryptase,
      carboxypeptidase A, and Fc epsilon RI. These cells were also found in the skin,
      spleen, and lymph nodes where they presumably expand, differentiate, and mature,
      assuming the mast cell phenotype for those tissues characterized by
      metachromasia, expression of a full range of mast cell-related secretory granule
      proteases, and ultrastructural appearance. The presence of SCF on the surface
      membrane of the circulating, highly immature mast cells suggests an autocrine
      regulation of the c-kit-SCF interaction.

PMID- 8876561
TI  - A modified, prolonged desensitization protocol in carboplatin allergy.

PMID- 8876562
TI  - Interpretation of rhinoconjunctivitis quality of life questionnaire data.

PMID- 8876563
TI  - Desensitization for fluconazole hypersensitivity.

PMID- 8876564
TI  - Familial cholinergic urticaria.

PMID- 8876565
TI  - Cefazolin specific side chain hypersensitivity.

PMID- 8876566
TI  - Oral allergy syndrome after ingestion of salami in a subject with
      monosensitization to mite allergens.

PMID- 8876567
TI  - Failure of a breath-actuated bronchodilator inhaler to deliver aerosol during a
      bout of near fatal asthma.

PMID- 8876568
TI  - Mite allergen (Der p 1) on children's clothing.

PMID- 8876569
TI  - Absence of modification of endogenous soy allergens.

PMID- 8876570
TI  - Hand dermatitis: a risk factor for latex hypersensitivity.

PMID- 8876571
TI  - Innominate osteotomy in adolescents and adults who have acetabular dysplasia.
AB  - The results were evaluated for twenty-eight adolescents and adults (thirty-one
      hips) who had had a Salter innominate osteotomy because of acetabular dysplasia
      and pain in the hip. The mean age at the time of the index operation was twenty
      two years, and the mean duration of radiographic follow-up was seventy-one
      months. Radiographs were available for twenty-five patients (twenty-eight hips)
      at the most recent follow-up evaluation. The radiographic evaluation included
      determination of the acetabular angle, the center-edge angle, the coverage of the
      femoral head, the height of the joint space, and the Shenton line. Compared with
      the preoperative measurements, the acetabular angle had decreased by a mean of
      10.0 degrees, the center-edge angle had increased by a mean of 13.2 degrees, and
      the coverage of the femoral head had increased by a mean of 15 per cent (p <
      0.001 for all three values). The height of the joint space had decreased but,
      with the numbers available, this change was not significant. The Harris hip
      scores, determined for twenty patients (twenty-one hips), improved from a mean of
      71.2 points preoperatively to a mean of 88.3 points at the latest follow-up
      evaluation (p < 0.001). A questionnaire, completed by twenty-seven patients
      (thirty hips), revealed that twenty-one patients (78 per cent) were satisfied
      with the result of the operation; twenty-two patients (81 per cent) said that
      they would recommend this procedure to others who had a similar condition. The
      pain score (with 1 point indicating mild pain and 5 points indicating severe
      pain) improved from a mean of 3.7 points preoperatively to a mean of 2.5 points
      at the latest follow-up evaluation (p < 0.001). There were six postoperative
      complications. One patient had a non-union; one, an infection; one, heterotopic
      bone; and three, numbness. Two of these patients subsequently had a total hip
      arthroplasty at ninety-eight and 150 months, and one patient had a Chiari
      osteotomy at twenty-two months. Our findings demonstrate that the Salter
      innominate osteotomy provides notable clinical improvement as well as
      improvements in the radiographic measurements of the hip in patients who have
      acetabular dysplasia.

PMID- 8876572
TI  - Isolated proximal femoral osteotomy for treatment of residua of congenital
      dysplasia or idiopathic osteoarthrosis of the hip. Five to ten-year results.
AB  - We retrospectively reviewed the five to ten-year results of an isolated proximal
      femoral osteotomy in two groups of patients. One group consisted of seventeen
      patients (eighteen hips) who had a residual deformity resulting from congenital
      dysplasia of the hip; there were fifteen women and two men, and the mean age was
      thirty-three years (range, twenty-four to fifty-eight years). The other group
      included sixteen patients (sixteen hips) who had idiopathic osteoarthrosis; there
      were three women and thirteen men, and the mean age was forty-eight years (range
      thirty-eight to fifty-seven years). Both groups were evaluated clinically and
      radiographically, at a mean of 6.1 years (the patients who had residua of
      congenital dysplasia) and 6.7 years (the patients who had idiopathic
      osteoarthrosis). Of the seventeen patients who had residual deformity resulting
      from congenital dysplasia, eight (eight hips) were completely satisfied with the
      result of the osteotomy at least five years postoperatively; the joint space was
      improved in five of these patients (five hips) at the latest radiographic
      evaluation. Nine patients (ten hips) were not satisfied with the result of the
      osteotomy at the time of the most recent follow-up; four of the (four hips) had a
      subsequent total hip arthroplasty. Of the sixteen patients who had idiopathic
      osteoarthrosis, six were completely satisfied with the result of the osteotomy at
      least five years postoperatively. The joint space was improved in only two
      patients at the latest radiographic evaluation. The osteotomy did not provide
      lasting pain relief for seven patients, all of whom had a subsequent total hip
      arthroplasty. In both diagnostic groups, the most enduring clinical improvement
      occurred in hips that had the least evidence of osteoarthrotic changes on the
      preoperative radiographs. In addition, in the group that had residual deformity
      resulting from congenital dysplasia, the best outcomes were seen in hips with the
      least degree of acetabular dysplasia.

PMID- 8876573
TI  - Analysis of the gait of adults who had residua of congenital dysplasia of the
      hip.
AB  - Twenty-one adult subjects who had symptomatic residua of unilateral congenital
      dysplasia of the hip, with various degrees of degenerative changes, were studied
      with respect to the physical and radiographic findings and gait performance.
      Three-dimensional body reconstruction; the Trendelenburg sign; spatiotemporal
      parameters of stride; ground-reaction forces; kinematics of the hip, knee, and
      ankle; moments of forces; and joint powers were evaluated bilaterally. The
      kinematic and kinetic parameters of the affected limb were compared with those of
      the unaffected limb and with those of the limbs of normal control subjects.
      Correlations between changes in selected gait parameters and the clinical and
      radiographic signs of impairment of the hip were demonstrated. The results are
      discussed in relation to the possible mechanisms underlying the observed
      alterations and in view of possible operative interventions.

PMID- 8876574
TI  - The Ilizarov method for correction of complex deformities. Psychological and
      functional outcomes.
AB  - We reviewed the psychological profile and functional ability of forty-five
      children (fifty-two extremities) who had had correction of deformities of the
      lower extremities with the Ilizarov method. Psychological changes were evaluated
      with the Post-Hospitalization Behavior Questionnaire and the Children's
      Depression Inventory, and the functional status was measured with the Children
      Health Information Service Rand Scale. The over-all satisfaction of the patient
      with regard to the outcome of the operation was assessed as well. The operations
      were performed between 1988 and 1992. The average age at the time of the
      operation was twelve years (range, three to eighteen years), and the average
      duration of follow-up was thirty-six months (range, twenty-four to seventy-two
      months). The lengthening index, duration of lengthening, and average number of
      complications were similar to those reported in other studies. All of the
      children had a normal psychological score, forty-two had no limitations in daily
      activities, and thirty-seven were satisfied with the over-all result.

PMID- 8876575
TI  - Failure of a non-porous-coated acetabular component inserted without cement in
      primary total hip arthroplasty.
AB  - Thirty-four patients (thirty-eight hips) had a primary total hip arthroplasty
      with insertion of a non-porous-coated titanium-alloy acetabular component without
      cement. This component is initially stabilized with use of a central acetabular
      polyethylene peg, which is inserted into the pelvis, as well as supplementary
      cortical-bone screws inserted into the ilium. The original diagnosis was
      degenerative joint disease in thirty-four hips and avascular necrosis in four
      hips. Twenty-five femoral components were inserted with cement, and thirteen non
      porous-coated femoral implants were inserted without cement. The acetabulum was
      prepared with so-called line-to-line reaming. Thirty-five hips in thirty-one
      patients were available for clinical and radiographic follow-up at a mean of 4.5
      years (range, two to seven years). Serial measurements of the position of the
      acetabular component revealed that eighteen cups (51 per cent) had migrated. Of
      these, eleven had been revised. Radiolucent lines of at least one millimeter in
      thickness at the bone-prosthesis interface were noted adjacent to all but six of
      the acetabular components. Although this series was small, it demonstrates an
      unacceptably high rate of failure of non-porous-coated acetabular components
      after a relatively short duration. We question the efficacy of this acetabular
      component, inserted without cement, as part of a primary total hip arthroplasty.

PMID- 8876576
TI  - Pain in the posterior aspect of the ankle in dancers. Differential diagnosis and
      operative treatment.
AB  - A retrospective review was performed of the results of operative treatment of
      stenosing tenosynovitis of the flexor hallucis longus tendon or posterior
      impingement syndrome, or both, in thirty-seven dancers (forty-one operations).
      The average duration of follow-up was seven years (range, two to thirteen years).
      The results were assessed with use of a questionnaire for all patients, and a
      clinical evaluation was performed for twenty-one patients (twenty-two ankles).
      Twenty-six operations were performed for tendinitis and posterior impingement;
      nine, for isolated tendinitis; and six, for isolated posterior impingement
      syndrome. A medial incision was used in thirty-three procedures; a lateral
      incision, in six; an anterior and a medial incision, in one; and a lateral and a
      medial incision, in one. Thirty ankles had a good or excellent result; six, a
      fair result; and four, a poor result. (The result of the second procedure on an
      ankle that was operated on twice was not included.) The result was good or
      excellent for twenty-eight of the thirty-four ankles in professional dancers,
      compared with only two of the six ankles in amateur dancers.

PMID- 8876577
TI  - Continuous postoperative infusion of a regional anesthetic after an amputation of
      the lower extremity. A randomized clinical trial.
AB  - We performed a prospective, randomized clinical trial to determine whether
      continuous infusion of bupivacaine hydrochloride decreased the use of narcotics
      for the relief of pain after an amputation. Twenty-one patients who were to have
      an amputation of the lower extremity because of ischemic necrosis secondary to
      peripheral vascular disease were divided into two groups with use of a table of
      random numbers. Group A (the treatment group) included nine patients who were to
      have a transtibial amputation, one patient who was to have a disarticulation at
      the knee, and one patient who was to have a transfemoral amputation. Group B (the
      control group) included seven patients, two patients, and one patient,
      respectively. After the amputation had been performed, a Teflon catheter was
      placed adjacent to the transected end of the sciatic or posterior tibial nerve.
      Postoperatively, the patients received continuous infusion of either bupivacaine
      (Group A) or normal saline solution (Group B) for seventy-two hours. Intravenous
      administration of morphine with use of a patient-controlled pump also was
      permitted during this period. The amount of morphine that was used was recorded
      meticulously. The patients in Group A used less morphine during the first and
      second days after the operation than did those in Group B. There was no
      difference between the groups with regard to the amount of morphine used on the
      third postoperative day. Over-all, eleven of fourteen patients who completed
      questionnaires reported a decrease in pain between the three and six-month
      evaluations. We concluded that continuous perineural infusion of an anesthetic
      appears to be a safe, effective method for the relief of postoperative pain but
      that it does not prevent residual or phantom-limb pain in patients who have had
      an amputation of the lower extremity because of ischemic changes secondary to
      peripheral vascular disease.

PMID- 8876578
TI  - Gait pattern in the early recovery period after stroke.
AB  - The gait patterns of eighteen patients who had had a single infarct due to
      obstruction of the middle cerebral artery were evaluated within one week after
      the patients had resumed independent walking and before a gait rehabilitation
      program had been initiated. Gait was analyzed with use of motion analysis, force
      plate recordings, and dynamic surface electromyographic studies of the muscles of
      the lower extremities. The patterns of motion of the lower extremity on the
      hemiplegic side had a stronger association with the clinical severity of muscle
      weakness than with the degree of spasticity, balance control, or phasic muscle
      activity. There was a delay in the initiation of flexion of the hip during the
      pre-swing phase, and flexion of the hip and knee as well as dorsiflexion of the
      ankle progressed only slightly during the swing phase. During the stance phase,
      there was decreased extension of the hip that was related to decreased muscle
      effort and a coupling between flexion of the knee and dorsiflexion of the ankle.
      The abnormal patterns of motion altered the velocity, the length of the stride,
      the cadence, and all phases of the gait cycle. The duration of the pre-swing
      phase was prolonged for the patients who had the slowest gait velocities. There
      also were abnormal movements of the upper extremity, the trunk, the pelvis, and
      the lower extremity on the unaffected side in an effort to compensate for the
      decreased velocity on the hemiplegic side. As velocity improved, these abnormal
      movements decreased. Therefore, the goal of therapy should be to improve muscle
      strength and coordination on the hemiplegic side, especially during the pre-swing
      phase.

PMID- 8876579
TI  - Compartment syndromes of the hand.
AB  - We retrospectively reviewed the records of nineteen patients who had been managed
      with fasciotomy because of compartment syndrome of the hand. The patients were
      five months to sixty-seven years old and included ten adults and nine children.
      Seventeen patients were followed for an average of twenty-one months (range, one
      to fifty-eight months), one patient was lost to follow-up after discharge, and
      one patient died four days postoperatively. All of the patients had a tense,
      swollen hand and elevated pressure in at least one interosseous compartment.
      Eight patients also had a compartment syndrome of the forearm. The compartment
      syndromes developed after intravenous injections (eleven patients); after a
      gunshot wound, a crush injury, or a complication related to the use of an
      arterial line (two patients each); and after a complication related to an
      arthrodesis of the wrist or a crush injury due to prolonged pressure on the upper
      extremity secondary to a drug overdose (one patient each). Fifteen patients had
      an obtunded sensorium-either because of a serious illness or injury or secondary
      to prolonged anesthesia-when the compartment syndrome was recognized. In thirteen
      of these patients, including eight children and five adults, the compartment
      syndrome developed because of a complication related to the intravenous or intra
      arterial administration of drugs. Carpal tunnel release and decompression of the
      involved compartments led to a satisfactory result for thirteen of the seventeen
      patients who were followed. The remaining four patients (including two children
      who had an amputation, one child who had impaired function of the hand secondary
      to brain damage, and one adult who had extensive involvement of the forearm and
      complete loss of function of the hand) had a poor result. All four of these
      patients had been obtunded when the compartment syndrome developed. The treating
      physician should maintain a high index of suspicion for a compartment syndrome of
      the hand when managing seriously ill, obtunded patients-particularly children-who
      are receiving multiple intravenous or intra-arterial injections.

PMID- 8876580
TI  - Differentiation of the bone-tissue remodeling response to axial and torsional
      loading in the turkey ulna.
AB  - The ability of bone tissue to differentiate between axial and torsional loading
      was determined with use of a functionally isolated turkey-ulna model of bone
      adaptation. Surface modeling and intracortical remodeling were quantified after
      four weeks of 5000 cycles per day of axial loading sufficient to cause 1000
      microstrain normal to the long axis of the bone (five ulnae), 5000 cycles per day
      of torsional loading sufficient to cause 1000 microstrain of shear strain (five
      ulnae), or disuse (six ulnae). Of these three distinct regimens, only disuse
      caused a significant change in gross areal properties (12 per cent loss of bone;
      p < 0.05) as compared with those in the contralateral, intact control ulnae
      (sixteen ulnae). This finding suggested that both axial and torsional loading
      conditions were suitable substitutes for functional signals normally responsible
      for bone homeostasis. However, the intracortical response was strongly dependent
      on the manner in which the bone was loaded. Axial loading increased the number of
      intracortical pores by a factor of seven as compared with that in the controls
      (246 +/- 40.5 compared with 36 +/- 8.5 pores); it also increased the area lost
      because of porosis as compared with that in the controls (1.39 +/- 0.252 compared
      with 0.202 +/- 0.062 square millimeter); however, the mean size of the individual
      pores was similar to that in the controls (0.00565 +/- 0.0019 compared with
      0.00561 +/- 0.0029 square millimeter). Conversely, torsional loading failed to
      increase substantially the number of pores (67 +/- 22.6 pores), the area of bone
      lost because of porosis (0.352 +/- 0.114 square millimeter), or the size of the
      pores (0.00525 +/- 0.0035 square millimeter) as compared with those in the
      controls. Although disuse failed to increase substantially the number of
      intracortical pores (59 +/- 22.4 pores), significant area (1.05 +/- 0.35 square
      millimeters; p < 0.05) was lost within the cortex because of a threefold increase
      in the mean size of each pore (0.0178 +/- 0.0126 square millimeter). It appears
      that bone tissue can readily differentiate between distinct components of the
      strain environment, with strain per se necessary to retain coupled formation and
      resorption, shear strain achieving this goal by maintaining the status quo, and
      axial strain increasing intracortical turnover but retaining coupling. While it
      is clear that load influences bone mass and morphology, it is also clear that
      specific parameters within the strain environment have distinct strategic roles
      in defining this architecture.

PMID- 8876581
TI  - Transfer of the levator scapulae, rhomboid major, and rhomboid minor for
      paralysis of the trapezius.
AB  - Twenty-two patients who had paralysis of the trapezius muscle secondary to injury
      of the spinal accessory nerve had transfer of the levator scapulae and rhomboid
      major and minor muscles. In each patient, function of the trapezius had failed to
      improve with either physical therapy or an operative attempt at neurolysis or
      reconstruction of the spinal accessory nerve. The etiology of the injury was
      biopsy of a cervical node in thirteen patients, trauma in seven, and radical
      dissection in the neck in two. All patients had pain, visible deformity, and
      dysfunction of the shoulder girdle. Physical examination revealed asymmetry of
      the neckline, drooping of the shoulder girdle with lateral displacement of the
      scapula, and weakness of active elevation. Fourteen patients had had an incorrect
      clinical diagnosis, and twelve patients had had an inaccurate or incomplete
      electromyographic examination. A long thoracic nerve palsy developed in three
      patients. At an average of seven and a half years (range, two to fourteen years),
      the result of the operative procedure, as determined with the American Shoulder
      and Elbow Surgeons Shoulder Evaluation Form, was excellent for thirteen patients,
      satisfactory for six, and unsatisfactory for three. All but three patients had
      adequate relief of pain and demonstrable functional improvement.

PMID- 8876582
TI  - Results of total elbow arthroplasty after excision of the radial head and
      synovectomy in patients who had rheumatoid arthritis.
AB  - We compared the results of twenty-three consecutive capitellocondylar total elbow
      arthroplasties in twenty-three patients in whom an excision of the radial head
      and synovectomy for rheumatoid arthritis had failed with those of twenty-three
      non-consecutive primary capitellocondylar total elbow arthroplasties in twenty
      three patients who had rheumatoid arthritis. The two groups were matched for age,
      gender, duration of follow-up, side of the operation, type of prosthesis, and
      operative approach. The average duration of follow-up was four years (range, two
      to fourteen years). At the most recent follow-up examination, use of a 100-point
      rating system demonstrated an improvement from an average preoperative score of
      21 points (range, 12 to 42 points) to an average postoperative score of 87 points
      (range, 17 to 97 points) for the group in whom an excision of the radial head and
      synovectomy had failed. The group that had primary arthroplasty demonstrated an
      improvement from an average preoperative score of 22 points (range, 7 to 42
      points) to an average postoperative score of 94 points (range, 85 to 100 points).
      The group that had primary arthroplasty had a significantly greater improvement
      in terms of relief of pain (p < 0.05), functional status (p < 0.01), and the
      elbow-rating score (p < 0.03) than the other group. Four patients who had had
      failure of an excision of the radial head and synovectomy and none of those who
      had primary arthroplasty needed an additional operative procedure. Six of the
      patients who had had a failed excision and synovectomy and none of the patients
      who had primary arthroplasty had instability of the elbow components. We
      concluded that, although excision of the radial head and synovectomy is a
      conservative and effective method of treating a painful rheumatoid elbow,
      conversion to a capitellocondylar total elbow arthroplasty is more difficult
      after such an operation and the results at a minimum of two years are inferior to
      those for primary capitellocondylar total elbow arthroplasty.

PMID- 8876583
TI  - The use of erythropoietin in the management of Jehovah's Witnesses who have
      revision total hip arthroplasty.
AB  - Five Jehovah's Witnesses (one man and four women) were managed with revision
      total hip arthroplasty. The average age of the patients at the time of the index
      operation was 66.4 years (range, fifty-eight to seventy-eight years). All of the
      patients received subcutaneous injections of recombinant human erythropoietin
      before the operation, at an initial dose of 100 international units per kilogram
      of body weight three times a week. The duration of preoperative treatment was
      determined by the hematocrit at the time of presentation. The hematocrit was
      monitored weekly, beginning with the second week of treatment, and the dose was
      adjusted accordingly until the time of the operation. Erythropoietin therapy was
      discontinued if the hematocrit exceeded 0.45 at any time. The hematocrit before
      the erythropoietin therapy was begun, at the time of admission to the hospital
      (one or two days preoperatively), immediately postoperatively, and at the time
      that the patient was discharged were recorded for this study. All five revision
      total hip arthroplasties were performed successfully without a blood transfusion.
      No patient had any complications associated with an excessive loss of blood or a
      low hematocrit. The average hematocrit was 0.395 (range, 0.317 to 0.447) before
      the erythropoietin therapy was begun and was 0.476 (range, 0.431 to 0.509) after
      treatment with erythropoietin and before the operation (that is, at the time of
      admission to the hospital). The average duration of erythropoietin therapy was
      twenty-six days preoperatively and 3.6 days postoperatively. The average
      hematocrit was 0.368 (range, 0.272 to 0.424) immediately after the operation and
      was 0.308 (range, 0.294 to 0.327) at the time of discharge from the hospital. No
      patient had evidence of deep venous thrombosis. This study illustrates that it is
      possible and apparently safe to optimize the hematocrit, by use of
      erythropoietin, in a patient who is scheduled for an operation. This may be
      particularly beneficial to a patient with anemia who has failure of a total hip
      arthroplasty. A relatively high hematocrit (0.45 to 0.50) preoperatively provides
      a relative margin of safety to a procedure that frequently involves a great deal
      of intraoperative blood loss. The use of erythropoietin preoperatively is
      particularly suited to joint replacements and revisions because of their elective
      nature and the moderately flexible timing associated with these procedures.

PMID- 8876584
TI  - The reliability of analysis of intraoperative frozen sections for identifying
      active infection during revision hip or knee arthroplasty.
AB  - A prospective study was performed to determine the reliability of analysis of
      intraoperative frozen sections for the identification of infection during 175
      consecutive revision total joint arthroplasties (142 hip and thirty-three knee).
      The mean interval between the primary and the revision arthroplasty was 7.3 years
      (range, three months to twenty-three years). To reduce selections bias, tissue
      was obtained for frozen sections during all revisions in patients who did not
      have active drainage from the wound or a sinus tract. Of the 175 patients, twenty
      three had at least five polymorphonuclear leukocytes per high-power field on
      analysis of the frozen sections and were considered to have an infection. Of
      these twenty-three, five had five to nine polymorphonuclear leukocytes per high
      power field and eighteen had at least ten polymorphonuclear leukocytes per high
      power field. The frozen sections for the remaining 152 patients were considered
      negative. On the basis of cultures of specimens obtained at the time of the
      revision operation, nineteen of the 175 patients were considered to have an
      infection. Of the 152 patients who had negative frozen sections, three were
      considered to have an infection on the basis of the results of the final
      cultures. Of the twenty-three patients who had positive frozen sections, sixteen
      were considered to have an infection on the basis of the results of the final
      cultures; all sixteen had frozen sections that had demonstrated at least ten
      polymorphonuclear leukocytes per high-power field. The sensitivity and
      specificity of the frozen sections were similar regardless of whether an index of
      five or ten polymorphonuclear leukocytes per high-power field was used. Analysis
      of the frozen sections had a sensitivity of 84 per cent for both indices, whereas
      the specificity was 96 per cent when the index was five polymorphonuclear
      leukocytes and 99 per cent when it was ten polymorphonuclear leukocytes. However,
      the positive predictive value of the frozen sections increased significantly (p <
      0.05), from 70 to 89 per cent, when the index increased from five to ten
      polymorphonuclear leukocytes per high-power field. The negative predictive value
      of the frozen sections was 98 per cent for both indices. The current study
      suggests that it is valuable to obtain tissue for intraoperative frozen sections
      during revision hip and knee arthroplasty. At least ten polymorphonuclear
      leukocytes per high-power field was predictive of infection, while five to nine
      polymorphonuclear leukocytes per high-power field was not necessarily consistent
      with infection. Less than five polymorphonuclear leukocytes per high-power field
      reliably indicated the absence of infection.

PMID- 8876585
TI  - Varus malalignment of the talar neck. Its effect on the position of the foot and
      on subtalar motion.
AB  - We performed an in vitro study on twelve specimens of the foot and ankle from
      cadavera to determine whether varus malalignment of the talar neck alters the
      position of the foot and subtalar motion. An osteotomy of the talar neck was
      performed, and the specimens were studied with and without removal of a medially
      based wedge of bone. Removal of the wedge produced an average varus malalignment
      of the talar neck of 17.1 +/- 2.4 degrees (range, 12.5 to 21.0 degrees). In the
      coronal plane, the average arc of motion of the subtalar joint decreased from
      17.2 +/- 3.3 degrees before the osteotomy to 11.7 +/- 2.9 degrees after the
      osteotomy and removal of the wedge. In the transverse plane, it decreased from
      17.5 +/- 2.9 degrees to 11.9 +/- 2.4 degrees. In the sagittal plane, it decreased
      from 8.9 +/- 2.4 degrees to 6.8 +/- 2.3 degrees. The decrease in subtalar motion
      was characterized by an inability to evert the foot; inversion was not limited,
      however. The malalignment produced an average of 4.8 +/- 1.2 degrees of varus
      deformity and 8.7 +/- 2.3 degrees of internal rotation of the hindfoot and an
      average of 5.5 +/- 2.0 degrees of varus deformity and 11.5 +/- 2.4 degrees of
      adduction of the forefoot. A linear correlation analysis was used to compare the
      change in subtalar motion and the position of the foot with the degree of varus
      malalignment at the talar neck. The correlation coefficient was 0.90 (p < 0.01)
      for subtalar motion, 0.76 (p < 0.01) for internal rotation of the calcaneus, and
      0.81 (p < 0.01) for adduction of the forefoot. This indicated a direct
      correlation between the degree of varus malalignment at the talar neck and the
      change in the position of the foot and in subtalar motion.

PMID- 8876586
TI  - Kienbock disease in a child who has cerebral palsy. A case report.

PMID- 8876587
TI  - Aneurysmal bone cyst of the atlas: operative removal through an anterolateral
      approach. A case report.

PMID- 8876588
TI  - Acute ischemia of the upper limb fifteen years after anterior dislocation of the
      glenohumeral joint and a modified Bristow procedure. A case report.

PMID- 8876589
TI  - Update on the genetic bases of disorders with orthopaedic manifestations.

PMID- 8876591
TI  - Treatment of idiopathic clubfoot. A thirty-year follow-up note.

PMID- 8876592
TI  - Treatment of idiopathic clubfoot. A thirty-year follow-up note.

PMID- 8876593
TI  - Antimicrobials in dentistry: with knowledge comes responsibility.

PMID- 8876594
TI  - The experimental gingivitis studies: the microbiological perspective.

PMID- 8876595
TI  - Variations in the social impact of oral conditions among older adults in South
      Australia, Ontario, and North Carolina.
AB  - Previous studies among older adults have demonstrated that oral disease
      frequently leads to dysfunction, discomfort, and disability. This study aimed to
      assess variations in the social impact of oral conditions among six strata of
      people aged 65 years and older: residents of metropolitan Adelaide and rural Mt
      Gambier, South Australia; residents of metropolitan Toronto-North York and non
      metropolitan Simcoe-Sudbury counties, Ontario, Canada; and blacks and whites in
      the Piedmont region of North Carolina (NC), United States. Subjects were
      participants in three oral epidemiological studies of random samples of the
      elderly populations in the six strata. Some 1,642 participants completed a 49
      item Oral Health Impact Profile (OHIP) questionnaire which asked about impacts
      caused by problems with the teeth, mouth, or dentures during the previous 12
      months. The percentage of dentate people reporting impacts fairly often or very
      often was greatest among NC blacks for 41 of the OHIP items. Two summary
      variables of social impact were used as dependent variables in bivariate and
      multivariate least-squares regression analyses. Among dentate people, mean levels
      of social impact were greatest for NC blacks and lowest for NC whites, while
      people from South Australia and Ontario had intermediate levels of social impact
      (P < 0.01). Missing teeth, retained root fragments, root-surface decay,
      periodontal pockets, and problem-motivated dental visits were associated with
      higher levels of social impact (P < 0.05), although there persisted a two-fold
      difference in social impact across the six strata after adjustment for those
      factors Among edentulous people, there was no statistically significant variation
      in social impact among strata. The findings suggest that there are social and
      cultural factors influencing oral health and its social impact, and that those
      factors differ most between dentate blacks and whites in NC.

PMID- 8876596
TI  - Total fluoride intake in children aged 3 to 4 years--a longitudinal study.
AB  - Several previous studies using food consumption tables or diet records have
      estimated that children aged 1 to 12 years resident in fluoridated (1 ppm) areas
      receive, on average, between 0.05 and 0.07 mg fluoride/kg body weight from foods
      and drinks alone. In this study, the duplicate-diet approach, which is a more
      accurate method of determining nutrient intake, was used to determine if levels
      of fluoride intake from foods and drinks are similar to those estimated from food
      consumption tables or diet records. Duplicate portions of all foods and drinks
      consumed over 24 hours by 66 children aged 3 to 4 years resident in fluoridated
      and low-fluoride areas of New Zealand were collected on three separate days over
      a period of 12 months and analyzed for fluoride. Fluoride intake from the use and
      ingestion of toothpastes and fluoride supplements was also determined for each
      child. It was hypothesized that the total amount of fluoride received by children
      in low-fluoride areas from diet, toothpastes, and fluoride supplements was
      similar to that received by children in fluoridated areas from diet and
      toothpastes. The mean fluoride intake from foods and drinks alone in the low
      fluoride areas was 0.008 +/- 0.003 mg/kg body weight (0.15 +/- 0.06 mg/day; n =
      34) and in the fluoridated areas was 0.019 +/- 0.009 mg/kg body weight (0.36 +/-
      0.17 mg/day; n = 32). The mean fluoride intake from foods and drinks and
      toothpastes in the low-fluoride areas was 0.027 +/- 0.012 mg/kg body weight (0.49
      +/- 0.25 mg/day) and in the fluoridated areas was 0.036 +/- 0.015 mg/kg body
      weight (0.68 +/- 0.27 mg/day). Fluoride intake from diet alone did not exceed
      0.04 mg/kg body weight (0.74 mg/day), and fluoride intake from diet and
      toothpaste did not exceed 0.07 mg/kg body weight (1.31 mg/day). The results
      suggest that levels of fluoride intake from foods and drinks alone as estimated
      by the duplicate-diet approach are much lower than previously estimated from food
      consumption tables or diet records. It was calculated that if all children in the
      low-fluoride areas were to take currently recommended dosages of fluoride
      tablets, which have been based on dietary surveys and diet records, then the
      total fluoride intake of some children in the low-fluoride areas would exceed
      that of their counterparts in the fluoridated areas. The results suggest that
      currently recommended dosages of fluoride tablets need to be further reduced if
      dental fluorosis in children is to be avoided.

PMID- 8876597
TI  - Use of the Weibull hazard model to estimate age-specific probability of permanent
      tooth loss.
AB  - In analysis of the probability of tooth loss with age, the exact time of tooth
      loss is often unknown, although it is clear whether a tooth remains or has been
      lost. That is, left censoring is inevitable during data sampling. This may
      provide a biased estimate if such data are dealt with by the product-limit
      method, which is a common method of survival analysis. To reduce such a bias in
      estimating the age-specific probability of tooth loss, we developed a survival
      analysis method taking left censoring into consideration. Four hundred and forty
      six panoramic radiographs obtained in a daily clinical practice were used. The
      frequency of tooth loss with age was assumed to follow the Weibull hazard model,
      and a likelihood function taking left censoring into consideration was defined to
      estimate the probability of tooth loss. The estimate obtained from our method was
      compared with that from the product-limit method to examine whether the effect of
      left censoring was reduced. We found that the probability of tooth loss estimated
      by the product-limit method was biased by left-censored data, and that the bias
      was reduced when our method was used. A Monte Carlo simulation study, in which
      the true tooth loss time was given, also showed that our method provided an
      estimate closer to the true value. Our method is considered to be more accurate
      in estimating the probability of tooth loss, since it reduces the bias caused by
      left-censored data.

PMID- 8876598
TI  - Form difference computations in restorative dentistry utilizing the macroelement
      method.
AB  - The comparison between the size and shape (form) of two structures or the
      analysis of one object under differing conditions is important in restorative
      dentistry. Despite rapid advances in digitizing technologies, form comparison is
      still mainly limited to scalar measurements. The objective of this study was to
      test the potential use of a newly developed tensorial morphometric difference
      technique, the macroelement method, in a model restrative system where the
      processing and materials properties are known duplication of a denture anchor in
      stone via polysulfide, addition silicone, and polyether impression materials.
      Nine machined landmarks were utilized to construct a nine-sided element for
      macroelement analysis. Macroelement results compared well with the known
      impression materials properties of polymerization shrinkage and incomplete
      recovery in terms of: (1) larger die diameter, (2) smaller die (vertically), (3)
      horizontal direction of maximum expansion, and (4) vertical direction of maximum
      contraction. Also, macroelement results along boundary lines were equal to the
      traditional form difference measure of change in length/length of those lines.
      The macroelement method provided results which are superior to those of
      traditional methods in that both (1) the magnitude and direction of difference at
      any point on the structure could be determined, and (2) the graphical
      representation of the results provides an intuitive appreciation of how and where
      the forms differ Therefore, since macroelement results: (1) compare well with
      known materials properties and traditional measures, and (2) have the above
      stated advantages, tensorial techniques such as the macroelement method, used in
      conjunction with new digitizing technologies, can be used better to describe the
      kinematics of form difference. With the description of the kinematics provided by
      the technique, the dynamic cause of the form difference can be ascertained with
      the investigators knowledge of materials. The investigators can then suggest
      changes to be made in materials and/or techniques that would enable the desired
      size and shape to be obtained.

PMID- 8876599
TI  - Finite element stress analysis of three filling techniques for class V light
      cured composite restorations.
AB  - An important disadvantage of current dental resin composites is polymerization
      shrinkage. This shrinkage has clinical repercussions such as sensitivity,
      marginal discoloration, and secondary caries. The objective of this study was to
      compare three filling techniques in terms of the transient stresses induced at
      the resin composite/tooth interface during polymerization. The techniques were:
      bulk filling (B), three horizontal increments (HI), and three wedge increments
      (WI). A simple Class V cavity preparation was modeled in finite element analysis.
      Polymerization shrinkage was simulated by a thermal stress analogy, thereby
      causing 1% shrinkage due to an arbitrary coefficient of thermal expansion.
      Interface normal and shear stresses were calculated at nine steps during
      polymerization, proceeding from 0% to 100% volume of cured resin. The importance
      of the interface transient stresses was revealed by the finding that, in most
      cases, their peak values exceeded the final or residual stress. Also, the WI and
      B techniques consistently exhibited the highest and lowest maximum transient
      stresses, respectively. These results from the simple model of a Class V
      restoration suggest that bulk filling of light-cured resin composites should be
      used in restorations which are sufficiently shallow to be cured to their full
      depth.

PMID- 8876600
TI  - Microcracks in dental porcelain and their behavior during multiple firing.
AB  - Dental porcelains rely on the high-thermal-expansion mineral leucite to elevate
      their bulk thermal expansion to levels compatible with dental PFM alloys. The
      microcracks that form around these leucite particles when cooled during porcelain
      manufacture are a potential source of change in bulk porcelain thermal expansion
      during fabrication of porcelain-fused-to-metal crowns and bridges. The purpose of
      the present study was to determine whether multiple firings of commercial dental
      porcelains could produce changes in microcrack density. Specimens of six
      commercial porcelains and the "Component No. 1" of the Weinstein patent were
      fabricated and subjected to 1, 2, 4, 8, and 16 firings. The microcrack densities
      were determined by quantitative stereology, whereby intersections of microcracks
      were counted with a test grid. The microcrack data were subjected to linear
      regression analysis and analysis of variance. The microcrack densities of four of
      the six porcelains and the Component No. 1 frit were not significantly affected
      by the number of firings (p > 0.05). One porcelain exhibited a weak but highly
      significant positive correlation between microcrack density and multiple firings
      (r2 = 0.24, p = 0.0003), while the remaining porcelain exhibited a weak but
      statistically significant negative correlation between microcrack density and
      multiple firings (r2 = 0.15, p = 0.006). The results of this study indicate that
      even for porcelains that exhibit a measurable change in microcrack density as a
      function of multiple firings, the magnitude of the increase or decrease in
      microcrack density after several firings is sufficiently small to cause only
      negligible shifts in porcelain bulk thermal expansion.

PMID- 8876601
TI  - Trial production of titanium orthodontic brackets fabricated by metal injection
      molding (MIM) with sintering.
AB  - Safety and esthetics are two indispensable factors to consider when fabricating
      orthodontic brackets. However, these factors are not easily achieved when
      conventional techniques (including forging and casting) are used in the mass
      production of titanium brackets, albeit the brackets exhibit excellent
      biocompatibility. In the present study, orthodontic brackets were manufactured by
      metal powder injection molding with sintering. Brackets with three different base
      designs were made and subjected to compression shear tests for evaluation of
      their bonding strength to enamel substrate. The shapes given to the dimple of the
      base were spherical, oval, and grooved. The maximum shear forces for each type
      were 11.1 kgf, 7.6 kgf, and 18.5 kgf, respectively. The bonding strengths of the
      titanium bracket were equivalent to those obtained with conventional stainless
      steel brackets. Moreover, uniform distribution of Vickers hardness values
      (average, 240 +/- 40 Hv) measured at three locations indicated that the titanium
      bracket was uniformly sintered. Accordingly, titanium brackets thus fabricated
      exhibit a potential for clinical application.

PMID- 8876602
TI  - Microstructure and segregation behavior of palladium in silver-copper-palladium
      alloys.
AB  - It has been reported that the addition of palladium can modify the microstructure
      and improve the properties of Ag-Cu eutectic alloy as well as admixed Cu-rich
      amalgam. The purpose of this work was to study the microstructure and segregation
      behavior of palladium in a series of Ag-Cu-Pd alloys. All microstructural and
      microchemical results consistently indicated a strong tendency for palladium to
      form the ordered Cu3Pd superlattice in the copper-rich phase of the present
      ternary alloys. Transmission electron microscopic examination indicated that, in
      addition to the large Cu-rich particles, numerous small (typically tens of
      nanometers) Cu-rich particles were distributed in the Ag-rich phase. In the
      alloys containing 10 and 15 wt% Pd, the Cu3Pd superlattice had an L1(2)-type
      crystal structure. In the alloy containing 20 wt% Pd, the Cu3Pd had a periodic
      (regular) APB structure. The solubility of palladium in the Cu-rich phase was
      always much larger than that in the Ag-rich phase. The ratio of the palladium
      concentration in the copper-rich phase to that in the silver-rich phase decreased
      with the overall palladium content.

PMID- 8876603
TI  - Microvascular luminal volume changes in aged mouse periodontal ligament.
AB  - Data for the microvascular bed in the aged periodontal ligament have not been
      established. This investigation tested the hypothesis that the luminal
      microvascular volume decreased in the aged ligament. Mice 35 days old and one
      year old were vascular-perfused and the mandibular first molar periodontal
      ligament processed for electron microscopy. Tissue quadrats from each
      circumferential third ligament region were recorded at 150-microns intervals from
      the alveolar crest to the apex for randomized sampling of blood vessel lumina.
      The data were analyzed with a generalized linear model at the p < 0.01 level for
      the interaction of the aging effect with differences across regions.
      Stereological parameters were established for vessel lumen volume, and for
      surface and length densities. Mean ligament width decreased from 119.9 +/- 16.94
      (micron +/- SE) in young mice to 60.0 +/- 10.58 (micron +/- SE) in aged mice. The
      luminal volume of 8.63 +/- 1.37 (% +/- SE) in young ligament increased to 9.83 +/
      2.14 (% +/- SE) in aged ligament. Collecting venules and the combined group of
      arterio-venous anastomoses with terminal arterioles showed a two-fold increase in
      luminal volume density (p < 0.01). In aged ligament, regional shifts affected the
      microvascular bed distribution, but these changes were not consistent across
      regions, or with depth. The average cross-sectional tissue area served per
      capillary decreased from 2117 microns 2 to 1451 microns 2 for young and old.
      Average ligament thickness served per capillary dropped from 52.5 microns to 27.5
      microns. These reductions in average diffusion distances indicated a change in
      the quality of the diffusion barrier with age.

PMID- 8876604
TI  - Expression of laminin 5, fibronectin, and epithelium-associated integrins in
      recurrent aphthous ulcers.
AB  - Recurrent aphthous ulceration (RAU) is characterized by an ulcerated lesion that
      persists longer than traumatic ulcers of similar size. This delayed healing phase
      of the lesion was investigated for extracellular matrix components and matrix
      receptors (integrins). The hypothesis tested was that aphthous ulcers may lack
      key extracellular matrix components, or their receptors, that are necessary for
      the migration of marginal keratinocytes from the ulcer edge. We
      immunocytochemically stained biopsy specimens of RAUs and non-involved mucosal
      specimens from HIV+ and non-infected individuals to investigate the presence and
      distribution of molecules reported to be associated with reepithelialization of
      mucosal and cutaneous wounds. Fibronectin, laminin type 5 (kalinin), and integrin
      subunits beta 1, beta 4, alpha 6, and alpha v were consistently found at the
      margins of RAU, as they are in traumatic ulcers. The alpha 5 and beta 6 subunits
      were not always present. We also found alpha v in the intact stratified squamous
      epithelium adjacent to ulcers. Immunohistochemical stains showed distruption in
      the deposition of laminin 5 and an apparent lack of fibronectin at the edges of
      some ulcers. Although these tissue results do not determine which integrin
      subunits are paired with each other, they do show some alterations in their
      expression in RAU. Absence of one or more of these molecules at the migrating
      front may contribute to delayed epithelial regeneration. It is likely that the
      absence or inappropriate expression of keratinocyte integrins or their
      extracellular matrix receptors occurs after the causative factors (currently
      unknown) of the lesion are gone. The reason for the altered expression of these
      molecules may be related to the secretory products (including lymphokines and
      proteinases) of the lymphocytic infiltrate.

PMID- 8876606
TI  - Treatment of human fetuses and induction of immunological tolerance in humans by
      in utero transplantation of stem cells into fetal recipients.
AB  - Since 1976, we have performed more than 240 fetal tissue transplants (FLTs) to
      treat 63 patients with severe immunodeficiency disease (IDD), with inborn errors
      of metabolism (IEM), or with severe aplastic anemia. In both IDD and IEM, FLT
      into postnatal recipients has demonstrated beneficial effects (67%) of the
      patients were either cured or improved significantly). In 1988, we developed in
      utero FLT into human fetuses, taking advantage of the immunological tolerance of
      young fetuses. The transplants have involved fetuses suffering from various
      diseases at 12-28 weeks postfertilization with 2 of the 6 cases eventually
      resulting in abortion. With the 4 other fetuses, a favorable outcome was
      observed: 3 children are now more than 4 years old, and are alive and well with
      evidence of engraftment, reconstitution of immunity, and partial correction of
      beta zero thalassemia. In the fourth case, the fetus is alive and well and birth
      is expected soon. In utero transplantation of stem cells is a therapy with
      remarkable advantages: (a) tolerance induction due to the immune immaturity of
      the host, (b) lack of graft-versus-host disease due to the immaturity of the
      donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) an
      optimal environment for donor fetal cell development in the vicinity of host
      fetal cells and growth factors.

PMID- 8876605
TI  - Expression of bone morphogenetic proteins by osteoinductive and non
      osteoinductive human osteosarcoma cells.
AB  - Freeze-dried Saos-2, human osteosarcoma cells, and extracts of Saos-2 cells
      contain all components necessary to induce ectopic new bone and marrow when
      implanted into athymic Nu/Nu nuce. On the other hand, human osteosarcoma cells of
      the U-2 OS strain failed to induce bone formation under the same experimental
      conditions. Our aim was to compare the relative expressions of known
      osteoinductive factors including bone morphogenetic proteins (BMPs) and
      transforming growth factor-beta (TGF-beta) in these two cell lines in an attempt
      to explain the unique bone-inducing ability of the Saos-2 cells. Saos-2 cells
      expressed mRNA for BMP-1, -2, -3, -4,-6, and TGF-beta 1. The non-osteoinductive U
      2 OS cells expressed BMP-2, -4, -5, -6, and -7 as well as TGF-beta 1 mRNA, while
      levels of BMP-1 and BMP-3 mRNA were either not detectable or detectable at a very
      low level in U-2 OS cells. The presence of BMP-1 and -4 protein was confirmed in
      Saos-2 cells by immunofluorescence, and TGF beta protein was demonstrated by
      bioassay in both cell types. These findings suggest that Saos-2 cells are endowed
      qualitatively and quantitatively with sufficient amounts of many bone
      morphogenetic proteins-especially BMP-1, -3, and -4-to confer osteoinductivity
      upon these cells. However, the absence of osteoinductivity in U-2 OS cells,
      despite significant mRNA expression levels of several bone morphogenetic
      proteins, suggests that, even though expression of one or more bone morphogenetic
      proteins may be present, it may not necessarily be sufficient to confer
      osteoinductivity upon U-2 OS cells. U-2 OS cells may be non-osteoinductive
      because (1) they contain inhibitors to the BMPs or secrete inhibitory binding
      proteins, (2) they do not process BMPs correctly, or (3) the BMPs are
      inappropriately localized and sequestered within the U-2 OS cells. Saos 2 cells
      may be osteoinductive because (1) they uniquely express BMP-1, (2) they express
      an appropriate combination of interactive BMPs at appropriate levels, and/or (3)
      the Saos-2 cells elaborate as-yet-unidentified osteoinductive factor(s).

PMID- 8876607
TI  - The gray zone between malignant and reactive processes in lymphoproliferative
      diseases.
AB  - The differences between reactive and malignant processes are sometimes blurred.
      Homogeneity is no longer a requisite for the diagnosis of lymphoma, as witnessed
      in mucosa-associated lymphatic tissue lymphoma and T-cell-rich B cell lymphoma,
      which are composed of an admixture of neoplastic clonal B cells and reactive T
      cells which occasionally are very prominent in the histological picture.
      Infectious mononucleosis, anaplastic large cell lymphoma, composite lymphoma and
      Hodgkin's disease, all share many similarities and may actually represent a
      continuous spectrum of pathological conditions. Immunodeficiency states, whether
      primary or acquired, are commonly associated with clonal lymphatic malignancies
      preceded by a polyclonal lymphoproliferative stage, which is usually reversible
      by reducing immunosuppression. The distinction between these stages is sometimes
      difficult to assess. Immunologists have so far failed to find a lymphatic tumor
      specific antigen, hence, monoclonality is usually based on a constellation of
      factors, namely homogeneity of the phenotypic expression of few antigens,
      aberrant expression of antigens and restricted expression of kappa- or lambda
      chains in malignancies expressing surface immunoglobulins. Nonrandom chromosomal
      translocations as well as other aberrations, usually important in the diagnosis
      of malignancy, are sometimes of limited value. This is mainly due to the
      existence of translocations [like t(14;18) and t(2;5)] in nonmalignant states,
      and their non-specificity [the existence of t(8;14) in Burkitt's lymphoma and
      large cell lymphoma, t(2;5) in Hodgkin's disease and anaplastic large cell
      lymphoma, and t(14;18) in large cell lymphoma evolving from follicular lymphoma
      and Burkitt's lymphoma]. The diagnostic tools available in 1995, although usually
      sufficient, are sometimes unable to distinguish between malignancy and
      reactivity. Some problematic cases will be more accurately defined as lying in
      the gray zone, or as belonging to a spectrum ranging between reactivity and
      malignancy.

PMID- 8876608
TI  - Chemotherapy with MECOP-B for intermediate-grade and high-grade non-Hodgkin's
      lymphoma in Saudi Arabia: clinical results and analysis of prognostic factors.
AB  - Between August 1985 and January 1994, 73 evaluable adult patients with bulky
      localized or advanced-stage, intermediate- and high-grade de novo non-Hodgkin's
      lymphoma (NHL) were treated with MECOP-B (methotrexate and leucovorin rescue,
      epirubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Over a
      median follow-up of 32 months (range, 4-98 months), 55 patients (75%) achieved
      complete remission (CR) (95% confidence interval, 81-69%) and 3 attained partial
      remission (PR) (4%) for an overall response rate of 79%. Using a multiple
      regression analysis where the dependent variable was response to therapy (CR vs.
      PR + treatment failure), poor performance status, and the presence of a bulky
      disease were negatively associated with the likelihood of achieving CR. Survival
      analysis showed that 49 (67%) patients (95% confidence interval, 74 and 60%) were
      alive, of whom 47 (64%) were disease-free. While the median survival has not been
      reached, the actuarial survival probability at 5 years +/- SE was 64 +/- 6%. Time
      to treatment failure for those attaining CR was also estimated. While the median
      survival has not been reached, probability of freedom from treatment failure at 5
      years +/- SE was estimated as 74 +/- 7%. However, the long-term CR (CR rate times
      disease-free survival rate) was only 48%, and the 'measurement of efficacy' was
      53%. These results were inferior to those from our earlier reports. The
      proportional hazards model of Cox identified poor performance status, older age,
      and high lactate dehydrogenase as factors with an adverse effect on survival.
      Using the results of the model, patients were categorized into three predefined
      risk groups with significant differences in outcome. Toxicity of the regimen was
      high, but comparable to that reported in the literature with a toxic death rate
      of 8%. We conclude that MECOP-B is an effective therapy for patients with
      aggressive NHL; however, based on the current results as compared with our
      earlier analysis, besides the emergence of prognostic factors, therapy of NHL
      should be individualized. Less expensive, less toxic regimens should be used for
      lower-risk patients, while the use of more intense, more toxic, more expensive
      programs should only be offered to those with a predicted poor outcome.

PMID- 8876609
TI  - Comparative study of three methods to detect free plasma antiplatelet antibodies.
AB  - We have compared three techniques for the detection of plasma circulating
      antiplatelet antibodies, i.e., the platelet suspension immunofluorescence test
      (PSIFT), the platelet radioactive antiglobulin test (PRAT), and the monoclonal
      antibody immobilization of platelet antigens (MAIPA). Frozen plasma samples from
      patients with idiopathic thrombocytopenic purpura or HIV-associated
      thrombocytopenia were used in the study. The PSIFT and PRAT showed the
      appropriate ease of performance necessary for screening purposes. The PSIFT is
      free of radioactivity hazards, but seemed to be less sensitive than the PRAT. The
      MAIPA is a useful tool to detect antibodies against glycoproteins (GPs) Ib/IX and
      IIb/IIIa. However, in comparison to PSIFT and PRAT, MAIPA is more time consuming,
      requires considerable technical expertise, and the identification of antiplatelet
      activity is highly dependent on the selection of an appropriate primary anti-GP
      monoclonal antibody. This could explain the lower prevalence of antiplatelet
      activity detected by MAIPA, in comparison to the frequency provided by the PSIFT
      and PRAT.

PMID- 8876610
TI  - In situ hybridization studies of cytomegalovirus and Epstein-Barr virus in
      reactive histiocytic hyperplasia with hemophagocytosis.
AB  - We studied 14 adult patients presenting with fever and cytopenia of the
      peripheral blood and histiocytic hyperplasia with hemophagocytosis (HHH) in the
      bone marrow regarding an association of cytomegalovirus (CMV) and Epstein-Barr
      virus (EBV) by using in situ hybridization (ISH) and also evaluated the clinical
      and laboratory findings according to the encountered organisms. ISH using a CMV
      RNA probe demonstrated infected cells in 6 out of 14 cases (43%), and ISH using
      an EBV EBER RNA probe demonstrated infected nuclei in 5 out of the same 14 cases
      (36%) of HHH. No cases showed a positive reaction with both probes. Three cases
      showed a negative reaction with both probes. The mean age of all patients was 29
      years; and that of the CMV-positive patients was 27 years and that of the EBV
      positive patients was 36 years. Organomegaly was found in 3 out of 6 CMV-positive
      patients (1 hepatomegaly, 1 splenomegaly, 1 hepatosplenomegaly), and 4 out of 5
      EBV-positive patients (lymphadenopathy in all 4 cases, hepatosplenomegaly in 2
      cases). One of the CMV-positive case had acute myeloblastic leukemia, and 2 EBV
      positive cases had underlying malignancy (1 Hodgkin's disease, 1 non-Hodgkin's
      lymphoma). Seven out of the 14 HHH cases (50%) died within several months after
      diagnosis. Nucleic acid hybridization methods can be used for the routine
      examination of the association of CMV or EBV.

PMID- 8876611
TI  - Erythrocyte production in iron deficiency anemia.
AB  - Erythrocyte production was measured in 21 iron deficiency anemia patients after
      therapy with parenteral iron. The red cell mass was measured twice with 51Cr and
      red blood cell survival by labeling with 51Cr. In all cases, erythrocyte
      production increased in the 12 h following parenteral iron administration
      (dextran or polysaccharide-iron oxide). Production increased sharply for 3 to 6
      days, remained high for 2 or 3 days and fell sharply thereafter. It is suggested
      that this fall is not due to a lack of available iron.

PMID- 8876612
TI  - Morbidity, beta S haplotype and alpha-globin gene patterns among sickle cell
      anemia patients in Kuwait.
AB  - Admission records of children with sickle cell anemia (SS), in the two main
      teaching hospitals in Kuwait, were reviewed for a 1-year period. The haplotypes
      of 92 beta s chromosomes (from 39 SS, 11 AS, 2 S beta-thalassemia [S beta-thal]
      and 1 SD individuals) were determined using an allele-specific oligonucleotide
      (ASO) hybridization technique, while the alpha-globin gene status of 27 SS and 33
      AS individuals, i.e. 120 chromosomes, was determined with a combination of
      polymerase chain reaction and AS techniques. A vasooclusive crisis was the most
      common (60.0%) cause of hospitalization, followed by infections (20%). Hospital
      admissions were most common during the hottest month of the year (July). Few
      complications of the disease were seen among patients on follow-up; however,
      splenomegaly was present in 24.0%, hepatomegaly in 15.2%, gallstones in 15.2% and
      aseptic necrosis of the femoral head in 6.1%. Haplotype 31 (Saudi Arabia/India)
      is the most frequent in this community, being present in 80.4% of the chromosomes
      tested; Benin haplotype 19 was found in 12.0% and Bantu haplotype 20 in 6.5%. Hb
      F in the haplotype 31 homozygotes and heterozygotes ranged from 11.4 to 35.1%
      (mean 22.5 +/- 5.2%). The frequency of alpha-thal determinants in the study was
      40.0%, the commonest being the -alpha 3.7-kb deletion (27.5%), the alpha 2
      polyadenylation signal (AATAAA-> AATAAG) mutation (10.2%) and the IVS-I 5' end
      GAGGT-GAGG->GAGG pentanucleotide (5 nt) deletion (3.3%). SS patients with
      coexistent alpha-thal trait did not have severe recurrent infections and none had
      gallstones. The high frequencies of the Saudi Arabia/India beta s haplotype and
      alpha-thalassemia trait contribute to the mild nature of SS disease among Kuwaiti
      Arabs comparable to that in eastern Saudi Arabia.

PMID- 8876613
TI  - Effects of hematopoietic growth factors on interleukin 6 secretion by blast cells
      derived from acute myelogenous leukemia patients.
AB  - Interleukin 6 (IL6) secretion by blast cells derived from peripheral blood of
      patients with acute myelogenous leukemia (AML) was characterized. IL6 secretion
      showed a wide variation both when AML blasts were cultured in medium alone and in
      the presence of exogenous cytokines. The level of IL6 secretion was significantly
      correlated to secretion of other cytokines (IL1 alpha, IL1 beta, granulocyte
      colony-stimulating factor, granulocyte-macrophage colony-stimulating factor,
      tumor necrosis factor alpha). IL1 beta, granulocyte-macrophage colony-stimulating
      factor, macrophage colony-stimulating factor and stem cell factor increased IL6
      secretion, whereas IL4 caused decreased IL6 secretion together with increased
      release of IL1 receptor antagonist.

PMID- 8876614
TI  - Globin mRNA in beta-thalassemia heterozygotes with different beta-thalassemia
      alleles and in heterozygotes for hereditary persistence of fetal hemoglobin.
AB  - Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine
      the alpha 2/alpha 1-, alpha/beta-, and gamma/beta-mRNA ratios in subjects with
      beta-thalassemia (beta-thal), hereditary persistence of fetal hemoglobin (HPFH),
      and normal adults. The alpha- and beta-globin gene mutations were characterized
      with gene mapping, PCR, and DNA sequencing. The average alpha 2/alpha 1-mRNA
      ratio was the same in normal adults and beta-thal heterozygotes with four alpha
      globin genes (2.61-2.63) or with an alpha-thal-2 trait (1.48-1.55). The average
      alpha/beta-mRNA ratios were 4.47 and 3.84 in normal adults with four alpha-globin
      genes and with alpha-thal-2 trait (-alpha/alpha alpha), respectively. There was
      an increase of approximately 50% in beta-thal heterozygotes with transcriptional
      mutants [-88 (C-->T) and -29 (A-->G)] with lower values (approximately 25%) in
      those with alpha-thal-2 trait (-alpha/alpha alpha). High alpha/beta ratios were
      also observed for heterozygotes for nonsense or frameshift mutants located in
      exon 1 or exon 2. Increases of approximately 150-165% were seen in subjects with
      RNA processing defects; an exception was the IVS-1-110 (G-->A) mutation with a
      normal value in the heterozygote. The increases were also less pronounced in
      heterozygotes for the codon (CD) 121 (G-->T) mutation and the CDs 134-137
      insertion/deletion. Normal alpha/(gamma + beta) values were seen in 3
      heterozygotes each with a different deletion involving part of the beta-globin
      gene. The presence of the silent beta-thal allele, -101 (C-->T), in trans to a CD
      8 (-AA) allele has a minor effect on the alpha/beta-mRNA ratio. The alpha/beta
      mRNA ratio in HPFH heterozygotes was approximately 145% of normal, but with a
      gamma-mRNA level of 35.4-44.7% the calculated alpha/(gamma + beta) ratio became
      as in normal adults. The RT-PCR methodology appears useful in expression studies
      in beta-thal (and HPFH) and values of mRNA appear to correspond to the type of
      prevailing mutation(s) and concomitant alpha-thal.

PMID- 8876615
TI  - Epstein-Barr-virus-associated lymphoproliferative syndrome in severe combined
      immunodeficiency: establishment of a lymphoblastoid cell line as an in vitro
      model for biological and therapeutic studies.
AB  - Patients with primary or secondary immunodeficiency are at high risk for B cell
      lymphoproliferative syndromes (LPS) that are generally Epstein-Barr virus (EBV)
      associated. We established a cell line, termed JuWa, from an immunoblastic
      lymphoma that developed in a child with severe combined immunodeficiency. JuWa
      cells were representative of the original lymph node as shown by a similar IgH
      gene rearrangement pattern. The cell line exhibited the typical features of a
      lymphoblastoid cell line (LCL): (1) growth pattern in large clumps, (2) lack of
      structural chromosome abnormalities, (3) type III latency with expression of EBV
      associated EBNA2 and LMP, as well as B cell activation markers CD23 and CD30,
      thereby showing characteristics of an EBV producer cell line, i.e. a latent
      infection with a small subpopulation of cells spontaneously entering the lytic
      cycle, (4) inducibility of the lytic cycle by IdU and TPA, leading to an increase
      of early antigen and viral capsid antigen-positive cells from 1 to 15-20%, and
      (5) elimination of the linear viral genomes by treatment with acyclovir (ACV),
      without affecting the circular episomal genomes. After withdrawal of ACV, viral
      replication resumed within 7 days. Thus, JuWa cells support the concept of the
      LCL-like features of LPS and lymphomas occurring in the setting of
      immunodeficiency. In our in vitro model, ACV treatment could effectively suppress
      the viral replication but not cure EBV infection of B cells.

PMID- 8876616
TI  - Modified oral anticoagulant potency in an amitriptyline-treated patient?
AB  - We report the case of a 74-year-old female patient who received the antide
      pressant amitriptyline because of a major depression. Incidence of acute lower
      extremity venous thrombosis required an additional oral anticoagulant therapy
      with phenprocoumon. During the simultaneous adjustment of both substances, the
      Quick value displayed great fluctuations which only disappeared after
      discontinuation of the amitriptyline medication. This finding is discussed as an
      aspect of a possible drug-drug interaction between amitriptyline and
      phenprocoumon.

PMID- 8876617
TI  - Thrombolytic therapy in pulmonary embolism of Behcet's disease.
AB  - We report the case of a patient with Behcet's disease who presented with deep
      vein thrombosis and pulmonary embolism. In spite of being treated initially with
      anticoagulants, corticosteroid and oral cyclophosphamide, the patient presented
      again with a new pulmonary embolism. This critical situation made us initiate
      thrombolytic therapy with a urokinase "bolus' followed by continuous infusion
      through a catheter into the pulmonary artery. Treatment response was good and 2
      years later there was no evidence of new thrombotic episodes.

PMID- 8876618
TI  - Report of a case of primary skeletal muscle lymphoma and review of the
      literature.
AB  - Primary extranodal lymphoma arising from skeletal muscle is rare. We describe a
      case of primary skeletal muscle lymphoma, diffuse large B-cell type. A review of
      the literature showed that it mostly involves the extremities, especially the
      thighs, in the elderly and has an aggressive histology of the B-cell
      immunophenotype. Different pathogenetic mechanisms for the occurrence of
      malignant lymphoma in extranodal sites are discussed.

PMID- 8876619
TI  - Soluble CD44 is not elevated in blood products.

PMID- 8876620
TI  - Expression of different forms of the heat-shock factor during the life cycle of
      the parasitic helminth Schistosoma mansoni.
AB  - HSE-HSF complexes from different stages of the life cycle of schistosome were
      analyzed by pore exclusion electrophoresis (estimates the size of the native DNA
      protein complex), and by U.V.-cross-linking followed by SDS-PAGE (estimates the
      size of the monomeric heat shock factor, HSF). The apparent M(r) values of the
      native and monomeric HSE-HSF complexes from schistosomula were 80,000 and 60,000,
      respectively. In adult worms M(r) values were 70,000 for the native HSE-HSF
      complex, 60,000 and 80,000 for the monomeric form. These findings indicate that:
      (1) schistosome express two (maybe three) forms of HSF, (2) different forms of
      HSF are expressed at different developmental stages. The findings that the native
      HSE-HSF complex and the monomeric HSF are of a similar size indicates that the
      complex contains a single HSF, or that the complex is a labile oligomer of HSF
      that decomposes into monomers during electrophoresis in a nondenaturing gel.

PMID- 8876621
TI  - Increased macrophage uptake of irreversibly glycated albumin modified-low density
      lipoproteins of normal and diabetic subjects is mediated by non-saturable
      mechanisms.
AB  - Diabetes mellitus is known as an independent risk factor in atherosclerosis.
      Among the prominent biochemical changes that occur in diabetic state, are the
      enhanced formation of advanced glycosylation end products (AGE) (especially
      linked to albumin and collagen) and the impaired oxidative-antioxidative balance.
      Previously, we have shown that AGE-albumin (AGE-Alb) significantly alters the
      physico-chemical characteristics of low density lipoproteins of normal (nLDL) and
      diabetic (dLDL) subjects. In this study we tried to establish if incubation of
      nLDL or dLDL, with AGE-Alb in autoxidative conditions, modifies the rate and/or
      the pathway of their uptake by macrophages. To this purpose, nLDL and dLDL were
      exposed to AGE-Alb, and after re-isolation and radiolabeling the lipoproteins
      were incubated with U937 or peritoneal macrophages (for various time and
      concentrations), in the absence or presence of different competitors (native LDL,
      acetylated LDL, AGE-Alb, mannan) or cytochalasin D. As controls, nLDL and dLDL,
      maintained in similar conditions, but without AGE-Alb, were used. The results
      showed that preincubation for 24 h and 72 h with AGE-Alb augmented the macrophage
      uptake for both nLDL and dLDL (1.7-fold). Either pre-incubated or not with AGE
      Alb, dLDL was taken up at a constantly higher rate than nLDL; the difference
      appeared more prominent at 72 h (1.5 vs. 4 micrograms LDL protein/mg cell
      protein). The increased level of glycation of native dLDL as compared to native
      nLDL (266 +/- 35 vs. 160 +/- 24 mmol HMF/mol apoB) as well as of the lipid
      peroxides (1.34 +/- 0.47 vs. 0.3 +/- 0.09 nmol MDA/mg apoB) could account for the
      greater uptake of dLDL at any preincubation time. Competition experiments
      indicated that, generally, incubation with AGE-Alb diminished the apo B100,E
      receptor-mediated uptake in favour of 'scavenger' receptor pathway and
      phagocytosis. Macrophage uptake of AGE-Alb modified dLDL was reduced
      approximately 30% by native nLDL, approximately 70% by acetylated LDL and
      approximately 38% by cytochalasin D. Together, these data suggest that the
      consequence of the alterations induced by AGE-Albumin on LDL is the increased
      macrophage uptake, via non-saturable pathways, that ultimately may lead to
      accelerated formation of atherosclerotic plaques in diabetics.

PMID- 8876622
TI  - Aging and polyamine acetylation in rat kidney.
AB  - The acetylation of polyamines was investigated in rat kidney as a function of
      age. The activity of cytosolic spermidine/spermine N1-acetyltransferase, the rate
      limiting enzyme in polyamine interconversion, increased from 3 to 36 months of
      age. The activity of cytosolic spermidine N8-acetyltransferase, an enzyme
      probably related to polyamine excretion, also increased. The activity of
      polyamine oxidase, which catalyzes the oxidative cleavage of polyamine N1-acetyl
      derivatives into putrescine, decreased until 24 months, when an accumulation of
      N1-acetylspermidine occurred. Subsequently, at 36 months, polyamine oxidase
      activity returned toward high values, in concomitance with the disappearance of
      N1-acetylspermidine, an increase in spermidine and putrescine, and a decline in
      spermine was observed. Our results show that in rat kidney during aging there is
      an activation of the acetylation and interconversion of higher polyamines into
      putrescine, which is considered an alternative pathway of spermidine and
      putrescine formation.

PMID- 8876623
TI  - Concentration of unsulfated lithocholic acid in portal and systemic venous
      plasma: evidence that lithocholic acid does not down regulate the hepatic
      cholesterol 7 alpha-hydroxylase activity in gallstone patients.
AB  - It has been proposed that lithocholic acid may have a physiological role for the
      regulation of bile acid synthesis in humans. In this study, the portal
      concentration and hepatic uptake of unsulfated lithocholic acid was determined in
      21 gallstone patients-untreated, cholestyramine-treated and chenodeoxycholic acid
      treated-at cholecystectomy. Lithocholic acid was analyzed by a combined gas
      liquid mass-fragmentographic technique. In most of the patients a liver biopsy
      was obtained for assay of the cholesterol 7 alpha-hydroxylase activity. The
      portal venous concentration of unsulfated lithocholic acid averaged 0.32 mumol/l
      in untreated patients, constituting about 4% of the total bile acids. The
      apparent hepatic uptake of lithocholic acid averaged 78%, being as high as that
      of cholic acid. No significant correlation was obtained between the portal venous
      concentration of unsulfated lithocholic acid and the hepatic cholesterol 7 alpha
      hydroxylase activity. This study thus confirms an enterohepatic circulation of
      lithocholic acid in humans. No evidence was obtained that the portal venous
      inflow of small amounts of lithocholic acid to the liver is of regulatory
      importance for the cholesterol 7 alpha-hydroxylase activity.

PMID- 8876624
TI  - Disorganization of microtubular network in postischemic liver dysfunction: its
      functional and morphological changes.
AB  - Microtubules in the hepatocytes have been implicated to serve as lines of
      cytoplasmic transport of secretory materials, but are highly labile structures
      sensitive to pathological conditions in the cytosol. We examined the role of
      ischemia/reperfusion-induced cytoskeletal alterations in postischemic liver
      dysfunction. Rabbit livers were subjected to 60-min warm ischemia followed by 1 h
      or 24 h of reperfusion. Liver function was assessed by directly measuring hepatic
      clearance of indocyanine green (ICG), an organic anion whose cytoplasmic
      transport is assumed to depend on intact microtubules, using near-infrared
      spectroscopy. Structural alterations of microtubules were observed
      immunohistochemically using tissue sections stained with monoclonal anti-beta
      tubulin antibody. ICG removal from hepatocytes into bile canaliculi deteriorated
      1 h but reversed 24 h after reperfusion. Immunohistochemistry showed
      fragmentation of microtubules at the end of liver ischemia. This cytoskeletal
      alteration was evident 1 h but was not observed 24 h after reperfusion. Treatment
      with prostaglandin E1 exerted its beneficial effect by preserving ICG clearance
      and microtubular network. These results demonstrate that liver ischemia and
      subsequent reperfusion both affect the organization of microtubular network and
      suggest that structural disruption of microtubules may be a cause of postischemic
      liver dysfunction.

PMID- 8876625
TI  - Translocation of protein kinase C-alpha, delta and epsilon isoforms in ischemic
      rat heart.
AB  - To explore the spatial and temporal localization of PKC isoforms during ischemia,
      we quantified PKC isoforms in the subcellular fractions in perfused rat heart by
      immunoblotting using specific antibodies against PKC isoforms. PKCs-alpha and
      epsilon translocated from the 100000 x g supernatant (S, cytosolic) fraction to
      the 1000 x g pellet (PI, nucleus-myofibril) and the 1000-100000 x g pellet (P2,
      membrane) fractions during 5-40 min of ischemia. PKC-delta redistributed from the
      P2 to the S fraction. A 50-kDa fragment of PKC-alpha appeared during ischemia
      possibly through calpain action. Immunohistochemical observations showed the
      different localizations of PKC-alpha, delta, and epsilon in the myocytes. The PKC
      assay displayed high basal levels of Ca(2+)-independent PKC, the activation of
      Ca(2+)-dependent PKC in the P1 and P2 fractions, and the activation of Ca(2+)
      independent PKC in the P1 fraction after 20 min of ischemia. These observations
      show that ischemia induces different patterns of translocation of the three PKC
      isoforms, suggesting differences in their roles.

PMID- 8876626
TI  - The formation of insoluble immune complexes between ovalbumin and anti-ovalbumin
      IgG occurs in at least two distinct phases dependent on reactant concentration
      and ionic strength.
AB  - The mechanism regulating the formation of insoluble immune complexes (IIC) in
      serum in certain disease states is not well understood. Ovalbumin and rabbit anti
      ovalbumin IgG was used to study the formation of IIC in vitro in a stirred
      reaction vessel; and the radii of IIC that formed was determined by light
      scattering techniques. Using an initial IgG concentration of 1 mg/ml at
      equivalence antigen:antibody ratio IIC formation was detected within 5 s, and the
      complexes increased in radii to approx. 100 nm after 20-30 s (phase 1). This was
      followed by a phase (phase 2) in which the complexes rapidly increased in radii
      to the point where Mie scattering was reached (approximately 200 nm). The time of
      onset of the second phase decreased with increasing initial IgG concentrations at
      a fixed antigen:antibody ratio; and was at a minimum at equivalence
      antigen:antibody ratio, but increased at both antigen and antibody excess ratios.
      Immune complexes formed using F(ab')2 fragment showed a similar pattern to those
      formed using IgG. A similar pattern was seen in the presence of the complement
      component C1q which potentiated IIC formation in phase 2, and human serum (1:10
      dilution) which attenuated IIC formation in both phases. For complex formation
      using IgG and ovalbumin the presence of NaC1 at concentrations up to 0.6 M led to
      a progressive increase in the time of onset of phase 2; potencies of inhibition
      by other sodium halides followed the lyotropic series NaF < NaC1 < NaI. The
      results suggest that formation of IIC occurs in at least two distinct phases, and
      that the second phase leading to the generation of very large insoluble complexes
      is associated with a rapid polymerisation of the complexes by a mechanism that is
      not dependent on Fc:Fc interactions.

PMID- 8876628
TI  - Unconjugated bilirubin inhibits in vitro cytotoxic T lymphocyte activity of human
      lymphocytes.
AB  - Septic complications have been major problems in the management of patients with
      obstructive jaundice and neonatal jaundice. This study investigates effects
      bilirubin on human T lymphocyte responses against allogeneic mixed lymphocyte
      reaction. In vitro exposure of human peripheral blood mononuclear cells (PBMNC)
      with unconjugated bilirubin at pathological levels (6 to 12 mg/dl) did not alter
      the subsets of CD3, CD4, CD8, CD14, CD19 and CD56 positive populations, or
      expression of costimulatory surface molecules CD2, CD3, CD4 and CD8. Further
      incubation of bilirubin-treated PBMNC with irradiated B lymphoid Raji cells after
      removal of the extracellular bilirubin resulted in a dose-dependent decrease of
      cytotoxic T lymphocyte (CTL) activity, DNA synthesis, and expression of Tac
      antigen (CD25) and transferrin receptor (CD71). However, no significant change of
      interleukin-2 (IL-2) production was observed after this incubation between
      bilirubin-treated and -untreated PBMNC. These results suggest that bilirubin
      inhibits the induction of CTL activity, and this defect may result from the
      impaired responsiveness against IL-2. These observations may help explain the
      increased infection observed in hyperbilirubinemic patients.

PMID- 8876627
TI  - Fibronectin fragments induce the expression of stromelysin-1 mRNA and protein in
      bovine chondrocytes in monolayer culture.
AB  - Addition of proteolytically generated fibronectin fragments (Fn-f) to cultured
      cartilage tissue causes greatly enhanced release of metalloproteinases (MMPs),
      such as pro-stromelysin-1 (proSln-1), and suppression of proteoglycan (PG)
      synthesis, through release of catabolic cytokines, while native fibronectin is
      ineffective. We have investigated whether enhanced release of proSln-1 was due to
      up-regulation of pro-Sln-1 mRNA. We report the addition of a 29-kDa (amino
      terminal heparin-binding Fn-f) or a 140-kDa (central cell-binding Fn-f) to bovine
      chondrocytes in monolayer culture causes a dose dependent increase in the
      expression of pro-Sln-1 mRNA and the greatly enhanced release of pro-Sln-1
      protein into the culture media. Up to 700 nM pro-Sln-1 was found in the
      conditioned media and metabolic labeling showed that it constituted a major
      portion of newly synthesized protein. A potential activator of pro-Sln-1,
      urokinase (u-PA), was released at elevated levels in the presence of the Fn-f
      while other activators, tissue plasminogen activator (t-PA) and plasmin
      activities were not detected. Addition of these activators to conditioned media
      did not allow conversion of pro-Sln-1 to active Sln-1. However, aminophenyl
      mercuric acid activated pro-Sln-1 to a 48-kDa Sln-1 form capable of degrading PG
      when added to cartilage suspensions. Gelatinase A mRNA was also enhanced,
      suggesting that the Fn-f may induce MMPs in general. However, the major regulator
      of Sln-1 activity, tissue inhibitor of MMPs form 1 (TIMP-1), was not induced at
      the gene level. Thus, a major effect of Fn-f on chondrocytes is to up-regulate
      pro-Sln-1 expression at the gene level, resulting in pro-Sln-1 as a major protein
      product.

PMID- 8876629
TI  - The enzymatic hydrolysis of 6-acylamino-4-methylumbelliferyl-beta-D-glucosides:
      identification of a novel human acid beta-glucosidase.
AB  - Fluorogenic 6-acylamino-4-methylumbelliferyl-beta-D-glucosides were found to be
      poor substrates for the three known human beta-glucosidases, i.e., lysosomal and
      non-lysosomal glucocerebrosidases and cytosolic broad-specificity beta
      glucosidase. However, homogenates of human tissues and human cell types showed
      significant enzymatic hydrolysis of 6-ethanoylamino-4-methylumbelliferyl-beta-D
      glucoside (EMGlc) due to the activity of a hitherto undescribed beta-glucosidase,
      called here EMGlc-ase. It was shown that the isozyme is hardly active towards 4
      methylumbelliferyl-beta-D-glucoside or glucosylceramide. EMGlc-ase exhibits
      maximal activity at pH 4.5 and 5.0 in the absence and presence of sodium
      taurocholate respectively. It is a soluble lysosomal enzyme with a discrete
      isoelectric point of about 5.0. EMGlc-ase is not inhibited by conduritol B
      epoxide, is activated by sodium taurocholate and binds strongly to Concanavalin
      A. This enzyme is not deficient in relation to Gaucher disease.

PMID- 8876630
TI  - DCC: is there a connection between tumorigenesis and cell guidance molecules?
AB  - Based on the findings reviewed above, DCC remains a strong candidate for the
      tumor suppressor gene in the 18q21 region that is presumed to be frequently
      inactivated in colorectal and a number of other cancer types. Although little is
      known of the specific mechanisms that account for the loss of its expression in
      most cancers, the recent studies demonstrating an association between loss of DCC
      expression in colorectal cancers and poor prognosis imply that DCC inactivation
      may have very significant effects on the cancer cell phenotype. DCC function in
      normal and cancer cells is still relatively poorly understood. However, recent
      studies have begun to provide some insights. Based on the results of a number of
      recent studies, DCC appears likely to have a role in significant role in
      differentiation, cell fate determination, and migration in the nervous system and
      perhaps other tissues as well. Though many additional studies are needed to
      characterize DCC function more definitively, it seems reasonable to predict that
      such studies are likely to provide new insights into growth control pathways in
      normal and cancer tissues.

PMID- 8876631
TI  - The role of nitric oxide (NO.) in the carcinogenic process.
AB  - The inflammatory process has long been known to be a risk factor for human
      cancers, particularly of the lung, bladder, colon, stomach, and female breast.
      Earlier hypothesis cited production of oxygen radicals, release of cytokines, and
      synthesis of prostaglandins and leukotrienes as biochemical modulators of the
      carcinogenic process. The discovery of NO. as a product of cells in the immune
      system has implicated this chemical in the mechanism of carcinogenesis,
      particularly when NO. is overproduced over a long period of time. After briefly
      reviewing the important chemical reactions of NO. under physiological conditions,
      we examine how the chemistry of its key reactants toward biologically important
      molecules relate to DNA damage and cytotoxicity. In these two processes, NO may
      play an important role in currently accepted models of multistage carcinogenesis.

PMID- 8876632
TI  - P-glycoprotein multidrug resistance and cancer.

PMID- 8876633
TI  - Papillomavirus infections--a major cause of human cancers.
AB  - The papillomavirus family represents a remarkably heterogeneous group of viruses.
      At present, 77 distinct genotypes have been identified in humans and partial
      sequences have been obtained from more than 30 putative novel genotypes.
      Geographic differences in base composition of individual genotypes are generally
      small and suggest a low mutation rate and thus an ancient origin of today's
      prototypes. The relatively small size of the genome permitted an analysis of
      individual gene functions and of interactions of viral proteins with host cell
      components. Proliferating cells contain the viral genome in a latent form, large
      scale viral DNA replication, as well as translation and functional activity of
      late viral proteins, and viral particle assembly are restricted to
      differentiating layers of skin and mucosa. In humans papillomavirus infections
      cause a variety of benign proliferations: warts, epithelial cysts,
      intraepithelial neoplasias, anogenital, oro-laryngeal and -pharyngeal papillomas,
      keratoacanthomas and other types of hyperkeratoses. Their involvement in the
      etiology of some major human cancers is of particular interest: specific types
      (HPV 16, 18 and several others) have been identified as causative agents of at
      least 90% of cancers of the cervix and are also linked to more than 50% of other
      anogenital cancers. These HPV types are considered as 'high risk' infections.
      Their E6/E7 oncoproteins stimulate cell proliferation by activating cyclins E and
      A, and interfere with the functions of the cellular proteins RB and p53. The
      latter interaction appears to be responsible for their mutagenic and
      aneuploidizing activity as an underlying principle for the progression of these
      HPV-containing lesions and the role of high risk HPV types as solitary
      carcinogens. In non-transformed human keratinocytes transcription and function of
      viral oncoproteins is controlled by intercellular and intracellular signalling
      cascades, their interruption emerges as a precondition for immortalization and
      malignant growth. Recently, novel and known HPV types have also been identified
      in a high percentage of non-melanoma skin cancers (basal and squamous cell
      carcinomas). Similar to observations in patients with a rare hereditary
      condition, epidermodysplasia verruciformis, characterized by an extensive
      verrucosis and development of skin cancer, basal and squamous cell carcinomas
      develop preferentially in light-exposed sites. This could suggest an interaction
      between a physical carcinogen (UV-part of the sunlight) and a 'low risk' (non
      mutagenic) papillomavirus infection. Reports on the presence of HPV infections in
      cancers of the oral cavity, the larynx, and the esophagus further emphasize the
      importance of this virus group as proven and suspected human carcinogens.

PMID- 8876634
TI  - A new concept in (adenoviral) oncogenesis: integration of foreign DNA and its
      consequences.
AB  - A new concept for viral oncogenesis is presented which is based on experimental
      work on the chromosomal integration of adenovirus DNA into mammalian genomes. The
      mechanism of adenovirus DNA integration is akin to non-sequence-specific
      insertional recombination in which patch homologies between the recombination
      partners are frequently observed. This reaction has been imitated in a cell-free
      system by using nuclear extracts from hamster cells and partly purified fractions
      derived from them. As a consequence of foreign DNA insertion into the mammalian
      genome, the foreign DNA is extensively de novo methylated in specific patterns,
      presumably as part of a mammalian host cell defense mechanism against inserted
      foreign DNA which can be permanently silenced in this way. A further corollary of
      foreign (adenovirus or bacteriophage lambda) DNA integration is seen in extensive
      changes in cellular DNA methylation patterns at sites far remote from the locus
      of insertional recombination. Repetitive cellular, retrotransposon-like sequences
      are particularly, but not exclusively, prone to these increases in DNA
      methylation. It is conceivable that these changes in DNA methylation are a
      reflection of a profound overall reorganization process in the affected genomes.
      Could these alterations significantly contribute to the transformation events
      during viral or other types of oncogenesis? These sequelae of foreign DNA
      integration into established mammalian genomes will have to be critically
      considered when interpreting results obtained with transgenic, knock-out, and
      knock-in animals and when devising schemes for human somatic gene therapy. The
      interpretation of de novo methylation as a cellular defense mechanism has
      prompted investigations on the fate of food-ingested foreign DNA. The
      gastrointestinal (GI) tract provides a large surface for the entry of foreign DNA
      into any organism. As a tracer molecule, bacteriophage M13 DNA has been fed to
      mice. Fragments of this DNA can be found in small amounts (about 1% of the
      administered DNA) in all parts of the intestinal tract and in the feces.
      Furthermore, M13 DNA can be traced in the columnar epithelia of the intestine, in
      Peyer's plaque leukocytes, in peripheral white blood cells, in spleen, and liver.
      Authentic M13 DNA has been recloned from total spleen DNA. If integrated, this
      DNA might elicit some of the described consequences of foreign DNA insertion into
      the mammalian genome. Food-ingested DNA will likely infiltrate the organism more
      frequently than viral DNA.

PMID- 8876635
TI  - Pattern of T-cell receptor delta gene rearrangement by Southern blotting and
      polymerase chain reaction technique in Hong Kong Chinese patients with non-T-cell
      hematological malignancies.
AB  - It has been recognized that clonal T-cell receptor delta (TCR delta) gene
      rearrangement is present in both T-and B-cell malignancies. The highly sensitive
      polymerase chain reaction (PCR) technique may be applicable to cases of leukemia
      and lymphoma of non-T-cell origin for detection of minimal residual disease
      (MRD). A PCR technique was used in this study to investigate the pattern of
      clonal TCR delta gene rearrangement in Hong Kong Chinese patients with non-T-cell
      hematological malignancies. Seventy-three patients with the diagnosis of acute
      leukemia and non-Hodgkin's lymphoma of non-T-cell origin were included in this
      study. There were 20 patients with common ALL (cALL), seven precursal B-cell ALL
      (PreB-ALL), 23 acute myeloid leukemia (AML), and 23 non-Hodgkin's lymphoma of B
      lineage (B-NHL). Clonal rearrangement was detectable by Southern analysis using a
      J delta 1 probe in 41 per cent of ALL of B-lineage but in none of the B-NHL or
      AML. The samples were also studied further by monoclonal PCR amplification for
      TCR delta gene rearrangement. Three different sets of primers were employed to
      detect clonal rearrangement of the TCR delta gene. The V delta 1(D)J delta 1
      recombination typically seen in T-cell malignancies were not seen in any of the
      of the non-T-cell malignancies. The V delta 2 (D) D delta 3 recombination was
      found exclusively in ALL of B-lineage and was seen in 73 per cent of the Southern
      positive cases. Although clonal TCR delta gene rearrangement was undetectable by
      Southern analysis in our AML cases, 26 per cent had a V delta 2(D)J delta 1
      recombination found by the PCR technique. Sensitivity of the PCR technique was
      determined by serial mixing and was up to 5-10 leukemic cells per 10(4) nucleated
      cells. It was apparent from this study that it was feasible to detect clonal TCR
      delta gene rearrangement by the PCR technique in a proportion of the cases of non
      T-cell hematological malignancies. The PCR technique can be applied to detect
      residual leukemic cells in marrow of patients in an apparent morphological
      complete remission. The value of this application requires further clinical
      evaluation and correlation.

PMID- 8876636
TI  - Modelling human leukemia and lymphoma in severe combined immunodeficient (SCID)
      mice: practical applications.

PMID- 8876637
TI  - Monoclonal antibody WGM1 directed against proteinase 3: an immunohistochemical
      marker for naphthol ASD chloroacetate.
AB  - Enzyme histochemistry for naphthol ASD chloroacetate (NASDCA, 'Leder's stain') is
      used to identify the granulocyte lineage ranging from promyelocytes to mature
      neutrophils and is an additional tool for the characterization of leukemias. We
      demonstrated for the first time that NASDCA activity can be detected by routine
      immunohistochemistry and immunocytochemistry using the monoclonal antibody WGM1
      directed against proteinase 3 (PR3; synonyms: Wegener's autoantigen,
      myeloblastin). Immunohisto- and immunocytochemical staining with WGM1 against PR3
      and enzyme histochemistry for NASDCA produced identical staining patterns in
      normal myelomonocytic cells and cells of myeloid leukemia. This was additionally
      proven by double immunostainings. We have also shown that PR3 is one of the
      specific proteinases responsible for hydrolysis of NASDCA.

PMID- 8876638
TI  - Detection of human T lymphotrophic virus type I (HTLV-I) DNA and mRNA in
      individual cells by polymerase chain reaction (PCR) in situ hybridization (ISH)
      and reverse transcription (RT)-PCR ISH.
AB  - Human T lymphotrophic virus type I (HTLV-I) proviral DNA and mRNA in the blood
      obtained directly from HTLV-I infected adult T cell leukemia (ATL) patients were
      amplified by the polymerase chain reaction (PCR), and reverse transcription (RT)
      PCR, and then were hybridized to fluorescein-labelled probes by means of in situ
      hybridization (ISH). Before the cytospin samples were prepared, heterogenous cell
      populations were reproducibly resolved into HTLV-I-positive and -negative
      distributions. Immunohistochemical staining was performed, using anti-fluorescein
      monoclonal antibody. Microscopic observations demonstrated a preserved cellular
      morphology. The intranuclear localization of amplified DNA products of proviral
      HTLV-I by PCR/ISH, and intracytoplasmic localization of amplified DNA of HTLV-I
      tax/rex mRNA by RT-PCR/ISH were maintained. In this study, about one in 10 HTLV-I
      provirus integrated cells expressed low copies of tax/rex mRNA. In HTLV-I
      negative cell lines, amplified DNA was not observed by either PCR/ISH or RT
      PCR/ISH. With the use of this technique it is thus possible to detect single-copy
      DNA and a few copies of mRNA, and it is therefore possible to study, not only
      suspended materials, but also other tissue materials for further
      characterization, in association with the localization of the HTLV-I infected
      cells.

PMID- 8876639
TI  - The mechanism of autoprocessing of the propeptide of prosubtilisin E:
      intramolecular or intermolecular event?
AB  - The propeptide of subtilisin, an alkaline serine protease, is known to be
      required for the folding of subtilisin, functioning as an intramolecular
      chaperone. Upon folding of prosubtilisin, the propeptide of 77 amino acid
      residues is autocatalytically cleaved. A histidine-tag was added to the N
      terminal end of prothiolsubtilisin E, or prosubtilisin(S221C), in which the
      active site serine residue at position 221 was substituted with cysteine. The
      histidine-tagged prosubtilisin(S221C) was denatured and immobilized on Ni-NTA
      resin. The denatured protein was then refolded on the resin, and the efficiency
      of the renaturation was determined by the efficiency of the propeptide cleavage.
      It was found that the cleavage of the propeptide was independent of the
      concentration of prosubtilisin(S221C), indicating that the autoprocessing is an
      intramolecular reaction. We also showed that prosubtilsin(S221A) can be
      autoprocessed if it is mixed with histidine-tagged prosubtilsin(S221C). These
      results demonstrate that prosubtilisin is intrinsically capable of being
      autoprocessed in an intramolecular manner, while it can also be processed in an
      intermolecular manner if it exists at higher concentrations.

PMID- 8876640
TI  - Evidence for intramolecular processing of prosubtilisin sequestered on a solid
      support.
AB  - Subtilisin E is synthesized in Bacillus subtilis as a preprosubtilisin. The
      prepeptide is removed by a signal peptidase, and the propeptide is cleaved from
      the mature protein by the catalytic domain of subtilisin itself in an
      autocatalytic fashion. A six residue histidine-tag was attached to the C terminus
      of prosubtilisin and mature subtilisin to enable immobilization on a metal
      chelating resin. Guanidine-HC1 denatured histidine-tagged subtilisin and
      prosubtilisin were immobilized on Co2+ charged Talon resin, then renatured by
      dialysis of the resin against renaturation buffer. Refolding of the immobilized
      prosubtilisin resulted in its quantitative autoprocessing and the formation of
      active enzyme. Mature subtilisin on the other hand refolded into an active
      conformation with very low efficiency, and at the same concentration the steady
      state rate attained was at least a 1000 times lower than that from prosubtilisin.
      The results give very strong support for an intramolecular autoprocessing pathway
      for prosubtilisin, in addition to an intermolecular one demonstrated before. The
      results also demonstrate rather convincingly the very much higher yield of active
      enzyme refolded from prosubtilisin than from mature protein under sequestered
      unimolecular conditions.

PMID- 8876641
TI  - Protein and DNA requirements for the transcription factor IIIA-induced distortion
      of the 5 S rRNA gene promoter.
AB  - Transcription factor-induced DNA distortion has become a common theme in
      eukaryotic gene regulation. A number of techniques have been applied to the study
      of transcription factor-induced DNA bending and flexibility including electron
      microscopy, circular permutation gel analysis, helical phasing gel analysis and
      cyclisation kinetics in solution. We have applied these techniques in order to
      assess the role that specific DNA sequences and protein domains of transcription
      factor IIIA (TFIIIA) play in the TFIIIA-induced distortion of the Xenopus 5 S
      ribosomal RNA gene promoter. Electron spectroscopic imaging analysis of
      TFIIIA:DNA complexes indicate that TFIIIA binding involves compaction of the 5 S
      promoter into a precise three-dimensional hairpin-shaped structure. This
      compaction can be detected utilising circular permutation gel analysis and the
      distortion results in an apparent bend angle of 55 to 60 degrees near the centre
      of the TFIIIA binding site. Helical phasing analysis demonstrates that the 60
      degrees bend angle as measured by circular permutation can be detected as a
      static bend directed towards the minor groove between bases +63 and +64 of the 5
      S rRNA gene. The amplitude of the TFIIIA:5 S gene phasing signal is similar to
      the phasing signal obtained utilising bacterial CAP:DNA complexes with bend
      angles of approximately 90 degrees. These results are supported by phased ligase
      mediated cyclisation kinetics in solution. Analysis of DNA deletion constructs
      indicate that the 5' A block of the internal 5 S gene promoter, which is required
      for transcriptional activity, is also required for TFIIIA-induced distortion of
      the 5 S gene promoter. Analysis of the N-terminal papain fragment of TFIIIA
      indicates that the 34 kDa zinc finger DNA binding domain is sufficient for
      compaction of the 5 S gene promoter. These results are discussed in relation to
      the modular model of TFIIIA:DNA interaction in which individual zinc fingers
      contribute to the protein-induced distortion of the DNA helix and overall DNA
      binding affinity in a complex, non-additive fashion.

PMID- 8876642
TI  - Identification of the bases in the ompF regulatory region, which interact with
      the transcription factor OmpR.
AB  - Expression of the outer membrane protein OmpF of Escherichia coli K-12 is
      influenced by a variety of environmental signals. Most of the signals are thought
      to regulate OmpF expression at the level of transcription initiation. A key
      element of this regulation is the interaction between the transcriptional factor
      OmpR and the cis-acting regulatory region of ompF. In this study, we used a
      combination of DNase I, dimethyl sulfate and hydroxyl radical footprinting
      analysis and DNA migration retardation assays to identify the bases within the
      ompF regulatory region that are in contact with OmpR. Our results indicate that
      the -107 to -39 region of ompF contains three individual binding sites and that a
      single OmpR-binding site is capable of interacting with two OmpR molecules. We
      also establish that a single OmpR-binding site is composed of two half-sites and
      that both half-sites are required for the formation of stable OmpR/DNA complexes.
      Comparisons of the sequences protected by OmpR indicate that an OmpR-binding site
      spans approximately 18 bp and has two highly conserved G/C base-pairs that are
      separated by three nucleotides. Although the three OmpR-binding sites we
      identified exhibit limited sequence similarity, this may reflect the fact that
      two of the sites are incapable of binding OmpR independently and can bind OmpR
      only if adjacent to another OmpR-binding site. Finally, our DNA migration
      retardation assays suggest that phosphorylation stimulates the cooperative
      interactions between OmpR molecules bound at neighboring sites. Therefore, this
      study provides a detailed understanding of how OmpR interacts with its binding
      sites immediately upstream of ompF and serves as a foundation for studying how
      phosphorylation of OmpR results in the regulation of ompF expression in response
      to environmental signals.

PMID- 8876643
TI  - The mechanism of recruitment of the lactate dehydrogenase-B/epsilon-crystallin
      gene by the duck lens.
AB  - In duck, the housekeeping enzyme lactate dehydrogenase B (LDH-B) and the lens
      structural protein epsilon-crystallin are encoded by the same single copy gene.
      Transcription of the gene is initiated from two closely spaced start sites, at 
      28 and +1. The usage of the downstream site is greatly enhanced in lens. Deletion
      mapping of the promoter shows that the region -70/+18 specifies the enhanced
      promoter activity in the lens. A critical role is played by the consensus Sp1
      binding site at -50; mutation of this site abolishes lens-preferred expression.
      Deletion of the +1 transcription initiation site also leads to a decrease in lens
      preferred expression, which can be restored by moving the -28 transcription
      initiation site downstream. By band shift experiments, supershift mobility assays
      and methylation interference assays, Sp1 was shown to bind to the Sp1 consensus
      binding site at -50 using either heart or lens nuclear extracts. Co-expression of
      Sp1 or Sp1-like factors inhibited the activity of an LDH-B/epsilon-crystallin
      promoter construct by approximately 60% in lens and by 40% in heart cells. Co
      expression of Pax-6, a transcription factor shown to be involved in the lens
      enhanced expression of a number of other crystallin genes, did not influence the
      promoter activity of the -130/+650 LDH-B/epsilon-crystallin promoter construct.
      In contrast to other crystallin promoters, the LDH-B/epsilon-crystallin promoter
      does not appear to contain a lens-specific element, rather our data lead to a
      model in which a factor transmitting the effect of Sp1, bound at -50, to the
      transcription initiation complex is responsible for the lens-preferred expression
      of the LDH-B/epsilon-crystallin promoter.

PMID- 8876644
TI  - Human immunodeficiency virus (HIV) Nef is an RNA binding protein in cell-free
      systems.
AB  - The function of human immunodeficiency virus nef gene product has been much
      debated but the precise activity of this protein in the HIV replication cycle
      remains unknown. HIV-1 Nef was obtained as a fusion protein with maltose binding
      protein (MBF), purified by amylose column chromatography and separated from MBP
      by cleavage with factor Xa. Purified HIV-1 Nef protein, but not the fusion
      protein MBP-Nef, binds to RNA in vitro as tested by three different assays,
      radioactive or non-radioactive. North-western analysis, UV cross-linking or band
      shift analysis. This activity was lost in a deletion mutant lacking 22 amino
      acids from the amino terminus of HIV-1 Nef, while a deletion of 44 residues from
      the carboxy terminus of the protein does not impair the RNA binding activity.
      Moreover, a single amino acid replacement, Arg to Gly at position 22 produces a
      Nef variant deficient in its ability to interact with RNA. Different Nef proteins
      from HIV-1, HIV-2 or SIV were fused to MBP and cleaved with factor Xa. The
      different Nef proteins were all endowed with RNA-binding capacity. Sequence
      similarities between several RNA binding proteins, including picornavirus 2C and
      different Nef proteins are observed. The function of Nef during the HIV
      replication cycle is discussed on the basis of the present findings.

PMID- 8876645
TI  - Secondary structure probing of potato spindle tuber viroid (PSTVd) and sequence
      comparison with other small pathogenic RNA replicons provides evidence for
      central non-canonical base-pairs, large A-rich loops, and a terminal branch.
AB  - Using PCR and in vitro transcription, linear (non-circular) unit-length (+)strand
      RNA molecules of a lethal PSTVd variant were produced which are able to initiate
      typical disease symptoms when inoculated into tomato. Non-denaturing gel
      electrophoresis shows that these transcripts can adopt the same two conformations
      as circular PSTVd molecules, namely a fast migrating rod-like and a slowly
      migrating cruciform structure. The rod-like conformer of two end-labelled
      transcripts was probed with nucleases and dimethyl sulphate, revealing that in
      solution its right part is identical to computer prediction. In the left part,
      however, three unique features could be substantiated. (1) In the central region
      a UV-cross-linkable loop is closed and thus contains non-canonical base-pairs
      ("loop E structure"). (2) Three large "pre-melting loops" are present at 25
      degrees to 37 degrees C. The structure of the leftmost one, which is A-rich and
      conserved in most viroids, correlates with pathogenicity. (3) Two small stem
      loops instead of an unbranched structure are found at the left terminus. These
      hairpins can form in all "large" viroids (approximately 300 nucleotides or
      longer), thus placing the dodecamer conserved among these viroids, GGUUCCUGUGGU,
      within the upper helix and the branch junction. A large viroid from Iresine lacks
      one of these hairpins, whereas all "small" viroids (approximately 300 nucleotides
      or smaller) lack both. In several plant virus satellite RNAs and the newt
      satellite RNA, the motif GAUUU(U) and dodecamer remnants appear in an equivalent
      structure comprising two or three hairpins. Using lead- and terbium-induced
      cleavage of the RNA, metal binding sites were found, mostly in loops. Thus,
      probing of PSTVd RNA and comparison with other.

PMID- 8876646
TI  - Minor groove binding ligands alter the rotational positioning of DNA fragments on
      nucleosome core particles.
AB  - We have used hydroxyl radical and DNase I footprinting to examine the interaction
      of four AT-selective minor groove binding ligands (Hoechst 33258, distamycin,
      netropsin and berenil) with DNA fragments which have been reconstituted with
      nucleosome core particles. Hydroxyl radical footprints of reconstituted tyrT DNA
      show that all four ligands induce changes in the phased cleavage pattern,
      consistent with the suggestion that they cause the DNA to rotate by 180 degrees
      on the nucleosome surface. This observation was confirmed by a series of hydroxyl
      radical and DNase I footprinting experiments on a synthetic DNA fragment
      containing five different (A/T)4 sites spaced ten bases apart, in phase with the
      nucleosomal repeat. This fragment produces a phased cleavage pattern when bound
      to the nucleosome cores, with minima in the AT regions, suggesting that these
      regions are positioned with their narrow minor grooves facing towards the protein
      surface. In the presence of the minor groove binding ligands the hydroxyl radical
      cleavage maxima are shifted by about five base-pairs. It appears that the ligands
      have caused the DNA to rotate by about 180 degrees on the protein surface; those
      DNA regions which were facing out are turned in and vice versa. Regions to which
      the ligands are bound are turned away from the protein surface, thereby
      minimising electrostatic repulsion between the cationic charges on the ligand and
      protein. The absence of any observable footprints in the AT-regions suggests that
      these changes are induced at low levels of occupancy.

PMID- 8876647
TI  - The structure of a phytocyanin, the basic blue protein from cucumber, refined at
      1.8 A resolution.
AB  - The crystal structure of the cucumber basic protein (CBP), a type 1 or blue
      copper protein, has been refined at 1.8 A resolution. The molecule resembles
      other blue copper proteins in having a Greek key beta-barrel structure, except
      that the barrel is open on one side and is better described as a "beta-sandwich"
      or "beta-taco". The Cu atom has the normal blue copper NNSS' co-ordination with
      bond lengths Cu-N(His39) = 1.93 A, Cu-S(Cys79) = 2.16 A, Cu-N(His84) = 1.95 A, Cu
      S(Met89) = 2.61 A. The Cu-S(Met) bond is the shortest so far observed in a blue
      copper protein. A disulphide link, (Cys52)-S-S-(Cys85), appears to play an
      important role in stabilising the molecular structure. It is suggested that the
      polypeptide fold is typical of a sub-family of blue copper proteins
      (phytocyanins) as well as a non-metalloprotein, ragweed allergen Ra3, with which
      CBP has a high degree of sequence identify. The proteins currently identifiable
      as phytocyanins are CBP, stellacyanin, mavicyanin, umecyanin, a cucumber peeling
      cupredoxin, a putative blue copper protein in pea pods, and a blue copper protein
      from Arabidopsis thaliana. In all except CBP and the pea-pod protein, the axial
      methionine ligand normally found at blue copper sites is replaced by glutamine.
      The structure of CBP was originally solved by the multiple wavelength anomalous
      scattering method, using data recorded at four wavelengths. All these data were
      included in the restrained least squares refinement. The final model comprises 96
      amino acid residues, 122 solvent molecules and a copper atom. Several residues
      are modelled as having more than one conformation. The residual R is 0.141 for
      41,910 observations (including Bijvoet-related observations) of 8.142 unique
      reflections in the resolution range 7 to 1.8 A.

PMID- 8876648
TI  - The three-dimensional structure of mammalian ribonucleotide reductase protein R2
      reveals a more-accessible iron-radical site than Escherichia coli R2.
AB  - The three-dimensional structure of mouse ribonucleotide reductase R2 has been
      determined at 2.3 A resolution using molecular replacement and refined to an R
      value of 19.1% (Rfree = 25%) with good stereo-chemistry. The overall tertiary
      structure architecture of mouse R2 is similar to that from Escherichia coli R2.
      However, several important structural differences are observed. Unlike the E.
      coli protein, the mouse dimer is completely devoid of beta-strands. The sequences
      differ significantly between the mouse and E. coli R2s, but there is high
      sequence identity among the eukaryotic R2 proteins, and the identities are
      localized over the whole sequence. Therefore, the three-dimensional structures of
      other mammalian ribonucleotide reductase R2 proteins are expected to be very
      similar to that of the mouse enzyme. In mouse R2 a narrow hydrophobic channel
      leads to the proposed binding site for molecular oxygen near to the iron-radical
      site in the interior of the protein. In E. coli R2 this channel is blocked by the
      phenyl ring of a tyrosine residue, which in mouse R2 is a serine. These
      structural variations may explain the observed differences in sensitivity to
      radical scavengers. The structure determination is based on diffraction data from
      crystals grown at pH 4.7. Unexpectedly, the protein is not iron-free, but
      contains one iron ion bound at one of the dinuclear iron sites. This ferric ion
      is bound with partial occupancy and is coordinated by three glutamic acids (one
      bidentate) and one histidine in a bipyramidal coordination that has a free apical
      coordination position. Soaking of crystals in a solution of ferrous salt at pH
      4.7 increased the occupancy on the already occupied site, but without any
      detectable binding at the second site.

PMID- 8876649
TI  - Crystal structure of R-phycoerythrin from Polysiphonia urceolata at 2.8 A
      resolution.
AB  - The structure of R-phycoerythrin (R-PE) from Polysiphonia urceolata was
      determined at 2.8 A resolution. The crystals belong to space group R3 with unit
      cell dimensions of a = b = 189.8 A, c = 60.1 A. The subunit composition of R-PE
      is (alpha 2 beta 2)3 gamma. The three-dimensional structure of R-PE was solved by
      the multiple isomorphous replacement method. After several cycles of model
      building and refinement, the crystallographic R-factor of the final model is
      18.0% with data from 10.0 to 2.8 A resolution. The four phycoerythrobilin
      chromophores alpha 84, alpha 140a, beta 84 and beta 155 in an (alpha beta) unit
      are each covalently bound to a cysteine residue through ring A. The phycourobilin
      chromophore is bound to cysteine beta 50 by ring A and bound to cysteine beta 61
      by ring D. The ring A and ring D of phycourobilin deviate from the conjugate
      plane formed by ring B and ring C and the four rings form a boat-shaped
      structure. R-PE contains a 34 kDa gamma subunit that is assumed to lie in the
      central channel of the molecular disc (alpha 2 beta 2)3. The energy transfer and
      relationship between cysteine residues and chromophores are discussed.

PMID- 8876650
TI  - Antibody-antigen interactions: contact analysis and binding site topography.
AB  - We have analysed antigen-contacting residues and combining site shape in the
      antibody Fv and Fab crystal structures now available from the Protein Data Bank.
      Antigen-contacting propensities are presented for each antibody residue, allowing
      a new definition for the complementarity determining regions (CDRs) to be
      proposed based on observed antigen contacts. Contacts are more common at CDR
      residues which are located centrally within the combining site; some less central
      CDR residues are only contacted by large antigens. Non-contacting residues within
      the CDRs coincide with residues identified by Chothia and co-workers as important
      in defining "canonical" conformations. An objective means of classifying protein
      surfaces by gross topography has been developed and applied to the antibody
      combining site surfaces. The surfaces have been clustered into four topographic
      classes: concave and moderately concave (mostly hapten binders), ridged (mostly
      peptide binders) and planar (mostly protein binders). We have determined the
      topographic classes for ten pairs of complexed and uncomplexed antibody-antigen
      crystal structures; four change topographic class on complexation. The results
      will be of use in antibody engineering, antigen docking and in clinical
      immunology. To demonstrate one application, we show how the data can be used to
      locate the antigen binding pocket on antibody structures.

PMID- 8876651
TI  - Glycinamide ribonucleotide transformylase undergoes pH-dependent dimerization.
AB  - Glycinamide ribonucleotide transformylase (GART) exhibits closely packed dimers
      in all crystal forms (pH 6.75), but was demonstrated to be monomeric in solution
      under conditions of optimal catalytic efficiency (pH 7.5). We undertook a study
      of the pH-dependent behavior of GART in solution to determine whether side-chain
      ionization is responsible for the observed difference in association state. In
      the pH range 6.8 to 7.5, dimeric GART reversibly dissociates into a monomeric
      form as demonstrated by dynamic light scattering. The data give a best fit to a
      cooperative three-proton transfer mechanism: [formula: see text] A comparison of
      normalized data obtained from difference UV-absorption spectroscopy with the
      dynamic light scattering data indicates that two or more tyrosine residues per
      monomer undergo a local conformational change concomitant with dimerization.
      Fluorescence studies show that the environment of one or both of the tryptophan
      residues distal to the dimer interface are also perturbed by dimerization.
      Fitting of the normalized titration curves yields an apparent pKa = 7.16(+/-0.02)
      and a subnanomolar KD for the transition. Examination of the dimer interface in
      the crystal structure indicates that there are two histidine residues, H54 and
      H73, that are likely responsible for the pH-dependent dimerization. There are
      also two tyrosine residues, Y67 and Y78, which are adjacent to the interface and
      which may be exposed during dimerization. Our study indicates that under
      physiological pH conditions, GART exists as a mixture of monomer and dimer in
      solution. Taken together, the fact that the monomer-dimer transition displays a
      sharp pH dependence, and the fact that the enzyme activity is maximal under
      conditions where it is fully monomeric, suggest that enzyme activity may be
      modulated by subtle pH changes in the cell.

PMID- 8876652
TI  - Structure-based calculation of the equilibrium folding pathway of proteins.
      Correlation with hydrogen exchange protection factors.
AB  - A new statistical thermodynamic formalism has been developed in order to describe
      the equilibrium folding pathway of proteins. The resulting formalism allows
      calculation of the probabilities that individual amino acid residues will be in a
      native or native-like conformation for any given degree of folding of the protein
      molecule. The residue probabilities are defined by the probability distribution
      of conformational states and can be used to calculate experimental quantities
      like native-state, hydrogen exchange protection factors. A combinatorial
      algorithm aimed at generating a large ensemble of conformational states (10(4) to
      10(6)) using the native structure as a template has been developed. The Gibbs
      energy and corresponding probability of each conformational state is estimated by
      using a previously developed structural parametrization of the energetics. The
      approach has been applied to five different proteins: hen egg-white lysozyme,
      equine lysozyme, bovine pancreatic trypsin inhibitor, staphylococcal nuclease and
      turkey ovomucoid third domain. The validity of the approach has been tested by
      comparing predicted and experimental hydrogen exchange protection factors. It is
      shown that for the above proteins 76%, 73%, 74%, 78% and 81% of all observed
      protection factors are predicted correctly. Furthermore, on average, the
      magnitude of the predicted protection factors, expressed as apparent free
      energies per residue deviate less than 1 kcal/mol from those obtained
      experimentally. These results represent the first attempt at predicting both the
      location and magnitude of hydrogen exchange protection factors from the high
      resolution structure of a protein. The good agreement between experimental and
      predicted values has permitted a close examination of the nature of the
      equilibrium folding intermediates existing under conditions of maximal stability
      of the native state.

PMID- 8876653
TI  - Human exposure to mercury: a critical assessment of the evidence of adverse
      health effects.
AB  - The ubiquitous nature of mercury in the environment, its global atmospheric
      cycling, and its toxicity to humans at levels that are uncomfortably close to
      exposures experienced by a proportion of the population are some of the current
      concerns associated with this pollutant. The purpose of this review is to
      critically evaluate the scientific quality of published reports involving human
      exposures to mercury and associated health outcomes as an aid in the risk
      evaluation of this chemical. A comprehensive review of the scientific literature
      involving human exposures to mercury was performed and each publication evaluated
      using a defined set of criteria that are considered standards in epidemiologic
      and toxicologic research. Severe, sometimes fatal, effects of mercury exposure at
      high levels were primarily reported as case studies. The disasters in Minamata,
      Japan, in the 1950s and in Iraq in 1971-1972 clearly demonstrated neurologic
      effects associated with ingestion of methylmercury both in adults and in infants
      exposed in utero. The effects were convincingly associated with methylmercury
      ingestion, despite limitations of the study design. Several well-conducted
      studies have investigated the effects of methylmercury at levels below those in
      the Iraq incident but have not provided clear evidence of an effect. The lower
      end of the dose-response curve constructed from the Iraq data therefore still
      needs to be confirmed. The studies of mercury exposure in the workplace were
      mainly of elemental or inorganic mercury, and effects that were observed at
      relatively low exposure levels were primarily neurologic and renal. Several
      studies have investigated effects associated with dental amalgam but have been
      rated as inconclusive because of methodologic deficiencies. In our overall
      evaluation, 29 of 110 occupational studies and 20 of 54 studies where exposure
      occurred in the natural environment provided at least suggestive evidence of an
      exposure-related effect.

PMID- 8876654
TI  - Comparative assessment of DNA adduct formation, Salmonella mutagenicity, and
      chromosome aberration assays as short-term tests for DNA damage.
AB  - DNA adduct formation assay (DAFA) was carried out to compare dose responses with
      the Ames test and chromosomal aberration test using aflatoxin B1 (AFB1) and
      benzo[a]pyrene (BaP). In the bacterial mutation test, AFB1 and BaP (0-1
      microgram/plate) were all positive in TA97a and TA100 with dose-related
      revertants. However, the slopes of the dose-response curves were gradual (slope
      0.55-3.73, r = .84-.98). In the chromosome aberration test, a significant
      increase in the percentage of chromosomal aberrations was obtained from male ICR
      mouse spleen cells treated with AFB1 and BaP, but a dose-related increase was
      insensitive (slope 0.09-0.23, r = .75-.78). The incidence of chromosomally
      aberrant spleen cells treated with BaP was significantly increased compared with
      AFB1. DAFA was performed in vitro with [3H]-AFB1 and [3H]BaP. These two
      carcinogens were able to induce genotoxicity and showed good dose-related
      increases in terms of DNA adduct formation (slope 0.78-1.28, r = 1.00).
      Coefficients of variation (CV) for the slope of each dose-response curve were
      much lower in DAFA in vitro (CV 15.09- 18.34%) than those in any other test (CV
      19.69-99.33%, Ames test; 18.89-44.58%, chromosome aberration test). Furthermore,
      DAFA in vivo was performed to investigate organotropic DNA adduct formation and
      persistence in Sprague-Dawley rats ip or orally treated with AFB1 and BaP. DNA
      adducts were monitored for 48-96 h by enzyme-linked immunosorbent assay (ELISA)
      using corresponding monoclonal antibodies, 6A10 and 8E11. DAFA in vivo
      demonstrated that the liver and kidney might be the probable target organs for
      AFB1 with the highest formation and persistence of DNA adducts and the lung and
      liver for BaP regardless of the route of administration. The results suggest that
      DAFA in vitro could be useful for detecting genotoxic compounds, and DAFA in vivo
      should also be considered as a good alternative method for the screening of organ
      specific chemical carcinogens.

PMID- 8876655
TI  - Ketone potentiation of haloalkane-induced hepatotoxicity: CCl4 and ketone
      treatment on hepatic membrane integrity.
AB  - Previous results in male Sprague-Dawley rats indicate that acetone (A), methyl
      ethyl ketone (MEK), and methyl isobutyl ketone (MiBK) pretreatments (3 d, p.o.)
      at a dosage of 6.8 mmol/kg potentiate CCl4 hepatotoxicity. The potentiation
      potency profile observed was MiBK > A > MEK. In the present study, male Sprague
      Dawley rats were treated for 3 d with 6.8 mmol/kg (p.o.) of A, MEK, or MiBK using
      Emulphor as vehicle (10 ml/kg). Rats were either killed 18 h after the last
      pretreatment or treated with CCl4 (prepared in corn oil) and then killed 48 h
      later. Livers were perfused; purified plasma membrane (PM), sinusoidal (SM) and
      basal canalicular membrane (BCM) fractions were prepared. Membrane fluidity was
      monitored by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH)
      or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). The
      following membrane enzymes were measured to monitor membrane purity and treatment
      effects: 5'-nucleotidase (5N), leucine aminopeptidase (LAP), and alkaline
      phosphatase (AP). Our results suggest that CCl4 modifies membrane integrity as
      indicated by a decrease in liver membrane 5N, LAP, and AP activity. CCl4 also
      increased the fluidity of the lipid and protein portions of the liver membranes
      as measured by the DPH and TMA-DPH fluorescence probes, respectively. Of the
      three ketones, only A altered CCl4 effects on plasma membrane enzymes and
      decreased BCM fluidity. The data only partially support increased susceptibility
      of liver membranes by ketone pretreatment as a factor implicated in the mechanism
      of potentiation of CCl4-induced hepatotoxicity.

PMID- 8876656
TI  - Toxicity of 2,4,4'-trichlorobiphenyl in rats following 90-day dietary exposure.
AB  - The toxicity of 2,4,4'-trichlorobiphenyl (PCB 28) was investigated in rats after
      a 90-d dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley
      rats were administered PCB 28 in the diet at 0, 0.05, 0.50, 5.0, or 50.0 ppm for
      13 wk. Growth rate and food consumption were not affected by treatment, and no
      clinical signs of toxicity were observed. Mottled liver was noted in both control
      and PCB-treated males, but was found with increased incidence in the highest
      treatment group. Increased urinary ascorbic acid and hepatic microsomal
      ethoxyresorufin O-deethylase activity were observed in the 50.0 ppm group of both
      sexes. The vitamin A content in liver, lung, and kidney was not significantly
      affected by treatment. Analysis of brain biogenic amines showed a decreased
      dopamine concentration in the substantia nigra region of female rats receiving
      0.5 ppm PCB 28 and higher doses. Female rats appeared to be more sensitive than
      males to the neurochemical effects of PCB 28. Dose-dependent histologic changes
      were observed in the thyroid and liver, with biologically significant changes
      occurring at 5.0 ppm and above. Based on these data, the no observable-adverse
      effect level (NOAEL) for this PCB congener was considered to be 0.5 ppm in diet
      or 36 micrograms/kg body weight/d.

PMID- 8876657
TI  - Effects of 3,3',4,4'-tetrachlorobiphenyl, 2,3,3',4,4'-pentachlorobiphenyl, and
      3,3',4,4',5-pentachlorobiphenyl on the developing chicken embryo when injected
      prior to incubation.
AB  - Great Lakes waterbird populations have experienced less-than-expected
      hatchability of eggs and a greater-than-expected incidence of developmental
      abnormalities. Such deleterious effects have been attributed to polyhalogenated
      hydrocarbons such as polychlorinated biphenyls (PCBs). PCBs are of primary
      concern since they are present in significant quantities in the environment.
      Specific PCB congeners, 3,3',4,4',5-pentachlorobiphenyl (IUPAC number 126),
      3,3',4,4'-tetrachlorobiphenyl (IUPAC number 77), and 2,3,3',4,4'
      pentachlorobiphenyl (IUPAC number 105), were injected (singly or in combination)
      into the yolks of White Leghorn chicken (Gallus domesticus) eggs prior to
      incubation. Teratogenicity was assessed in dead embryos and in hatchlings.
      Hatchlings were raised for 3 wk to assess body weight gain and mortality. At the
      end of the 3-wk period, chicks were subjected to necropsy and the brain, bursa,
      heart, liver, spleen, and testes were removed and weighed. All 3 congeners caused
      increased embryo mortality, with approximately 50% mortality occurring at 0.6,
      8.8, and 5592 micrograms/kg egg for congeners 126, 77, and 105, respectively. All
      three congeners also produced significantly more abnormalities than the vehicle.
      Chicks from PCB-injected eggs had lower body weights at wk 2 and 3 of age.
      Congener 126 caused lower relative bursa weights, congener 77 caused greater
      relative spleen weights and lower relative liver weights, and all three congeners
      caused relative heart weights to be greater when compared to control.

PMID- 8876658
TI  - Immunodominant Entamoeba histolytica antigens recognized by serum and intestinal
      antibodies after local or systemic immunization of mice with glutaraldehyde fixed
      trophozoites.
AB  - We performed an immunoblot analysis of the main E. histolytica proteins
      recognized by immune sera and intestinal fluids of Balb/c mice immunized with
      glutaraldehyde fixed trophozoites (GFT) by intragastric, rectal and
      intraperitoneal routes, to determine if there were differences in the amebic
      antigens immunodominantly recognized at mucosal and systemic levels. The antigen
      patterns recognized by mice immunized via intraperitoneal and rectal routes were
      complex and similar suggesting that the immunization route (systemic or local),
      does not influence the recognition pattern elicited at mucosal or systemic
      levels. However, the number of amebic bands recognized after intragastric
      immunization was very low. The molecular weights of the principal amebic proteins
      recognized by serum antibodies were 150-130, 116, 104, 84, 56, 42, 18, and 16
      kDa. The intestinal fluids of mice immunized via intraperitoneal and rectal
      routes contained antibodies that recognized five bands of 220-200, 150-134, 93
      84, 43-41, and 16-14 kDa. These results suggest that there are differences in the
      number of immunodominant amebic antigens recognized at mucosal and systemic
      levels. Moreover we found that the bands of 150, 39 and 19 kDa. were mainly
      recognized by IgG, whereas the bands of 116, 93, and 16 were mainly recognized by
      IgM, indicating differences between the antigens immunodominantly recognized by
      serum antibodies from different isotypes.

PMID- 8876659
TI  - The effect of tilsuprost on the liver mitochondria in taurocholate pancreatitis
      in rats with antecedent acute ethanol abuse.
AB  - The damage to the liver appears to be an important aspect of multisystem organ
      failure in acute pancreatitis with poor prognosis. The objective of this study
      was to evaluate the protective effect of stable prostacyclin analogue--tilsuprost
      on the liver energy metabolism in taurocholate pancreatitis in rats preceded by
      acute ethanol intake. The respiratory control ratio (RCR) and ADP/O ratio of
      liver mitochondria with glutamate+malate as substrates and mitochondrial DNP
      (uncoupler)-dependent ATPase activity were significantly depressed after 12 h of
      taurocholate pancreatitis-the effects that were not significantly aggravated by
      antecedent acute ethanol intake. Tilsuprost (0.3 mg/kg i.g.) given just before
      induction of pancreatitis partly prevented the impairment of mitochondrial
      oxidative and phosphorylative functions, however these positive effects were
      limited in acute pancreatitis preceded by acute ethanol intake. These results
      suggest that prostacyclin analogues could be effective in the treatment of
      hepatic complications in acute pancreatitis, however their effectiveness could be
      limited in the case of acute ethanol antecedent abuse.

PMID- 8876660
TI  - Cerebrospinal fluid distribution of opioids after intraventricular & lumbar
      subarachnoid administration in sheep.
AB  - The study of opioid distribution in blood and cerebrospinal fluid (CSF) is
      required to understand pharmacokinetic-pharmacodynamic relationships following
      lumbar intrathecal (it) and intracerebroventicular (i.c.v.) administration, and
      to investigate the contributions of spinal or supraspinal sites of action. The
      sheep model developed for pharmacokinetic study of analgesics allows atraumatic
      sampling of plasma and CSF after drug administration by the intravenous (i.v.),
      i.c.v., and it routes in an unanesthetized animal. Five adult female sheep were
      prepared with femoral vascular catheters, lumbar it and epidural cannulae, i.c.v.
      cannulae, and cisterna magna cannulae. Hydromorphone, methadone, naloxone, and
      [14C] sucrose were injected and collected by two methods: 1) injection into the
      i.c.v. cannula with lumbar CSF samples collected via the lumbar cannula and 2)
      injection into the lumbar cannula and cisternal CSF samples collected via
      ventriculocisternal cannula. Hydromorphone, morphine, and [14C] sucrose were
      detected at 90-105 min in lumbar CSF after i.c.v. injection. Hydromorphone and
      [14C] sucrose were detected in i.c.v. cerebrospinal fluid at 50 min after lumbar
      i.t. injection. Methadone was not detected in i.c.v. cerebrospinal fluid after
      i.t. injection, nor was methadone significantly detected in lumbar CSF after
      i.c.v. injection. These data indicate that i.c.v. and i.t. administration of
      lipophilic opioids produces CSF distributions different from those of hydrophilic
      opioids. This suggests that lipophilic opioids such as methadone or naloxone
      exert their effects predominantly on tissues near the site of injection. The
      study of i.t. and i.c.v. opiate administration and CSF pharmacokinetics may
      therefore have direct clinical implications.

PMID- 8876661
TI  - The protective role of zinc and N-acetylcysteine in modulating zidovudine induced
      hematopoietic toxicity.
AB  - The role of zinc and N-acetylcysteine (NAC) has been investigated in protecting
      the hematopoietic progenitor cells from zidovudine (AZT)-induced toxicity. Murine
      bone marrow progenitor cells (BMPC, 1x10(6)) were exposed to various
      concentrations (0.1-50 microM) of AZT in the presence and absence of zinc acetate
      (100 microM) or NAC (100 microM). The cell survival was determined by the colony
      forming assays of erythroid (CFU-E) and granulocytic (CFU-GM) lineage. The IC50
      values of AZT in the presence of zinc were increased approximately 3-fold (from
      3.0 to 9.5 microM) in the CFU-E assay and 7-fold (from 4.3 to 28.8 microM) in the
      CFU-GM assay whereas in the presence of NAC, the IC50 values were increased by 2-
      and 4-fold, respectively. To delineate the mechanism of significant protection of
      BMPC by zinc, the mRNA levels of metallothionein (MT) were monitored by using a
      31-mer cDNA probe. Zinc produced a concentration-dependent increase in the MT
      mRNA levels in BMPC. These results suggest that zinc and NAC dietary
      supplementation can be conveniently used to reduce AZT-induced bone marrow
      toxicity.

PMID- 8876662
TI  - Solubilization and characterization of binding sites for [3H]NE-100, a novel and
      potent sigma 1 ligand, from guinea pig brain.
AB  - The binding sites for [3H]NE-100, a newly defined sigma 1 ligand, was solubilized
      from guinea pig brain, using zwitterionic detergent 3-[(3-c holamidopropyl)
      dimethylamino]-1-propanesulfonate (CHAPS), and the properties of the solubilized
      binding sites were compared to those for [3H](+)-pentazocine, a selective sigma 1
      ligand. The pharmacological selectivity of solubilized sites for both [3H]NE-100
      and [3H](+)-pentazocine was identical to that obtained from membrane
      preparations. Stereoselectivity of benzomorphan such as pentazocine and SKF10,047
      was preserved in displacing [3H]NE-100 binding in solubilized preparations as
      observed in membrane preparations. The inhibitory potencies of several sigma
      ligands on [3H]NE-100 binding were similar to those on [3H](+)-pentazocine
      binding, indicating that the pharmacological characteristics of the binding sites
      for [3H]NE-100 are retained after solubilization. Phenytoin augmented the binding
      of [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine hydrochloride (3-PPP) to
      solubilized sigma binding sites while it had no effect on the binding of [3H]NE
      100. Furthermore, the inhibitory effect of putative sigma receptor agonists such
      as (+)-3-PPP and dextromethorphan were enhanced by phenytoin; the effects of
      haloperidol, a putative sigma receptor antagonist, were unaltered. Molecular
      weight of [3H]NE-100 binding protein was estimated to be 440KDa by Sepharose CL
      6B gel filtration chromatography, and the value was identical to that of [3H](+)
      pentazocine binding protein, a putative sigma 1 binding protein. These findings
      indicate that [3H]NE-100 binding sites are putative sigma 1 binding sites, and
      that NE-100 may act as an antagonist at sigma 1 binding sites.

PMID- 8876663
TI  - Localization of monoamine oxidases in human peripheral tissues.
AB  - Localization of monoamine oxidases (MAO) A and B and beta-adrenoceptors, was
      studied in aged human peripheral tissues (age 68-80 years) by quantitative
      autoradiography. The tissues analyzed were heart, lung, liver, kidney, spleen and
      duodenum. [3H]Ro41-1049 and [3H]lazabemide, two recently characterized selective
      radioligands were used to map MAO-A and MAO-B respectively. The regional pattern
      of distribution of MAO-A and MAO-B did not differ markedly, except in kidney and
      especially in duodenum. Highest levels of MAOs were measured in liver, and lowest
      in spleen. MAO-A was more abundant than MAO-B in lung and duodenal mucosa, and
      the reverse was true in myocardium. These results show marked differences in the
      abundance and patterns of distribution of MAOs, particularly MAO-B, in human and
      rodent peripheral tissues.

PMID- 8876664
TI  - The effects of atrial natriuretic peptide (ANP1-28) on corticotropin releasing
      factor in brain of rats.
AB  - We have shown that ANP has anxiolytic-like effects in behavioral studies. Since
      CRF is thought to be involved in emotional state of the brain, the present study
      was undertaken to follow the possible alterations in corticotropin-releasing
      factor-like immunoreactivity (CRF-LI) in different regions of the brain in rats
      following ANP treatment. CRF-LI immunoreactivity was determined in hypothalamic
      and extrahypothalamic brain areas after central injection of atrial natriuretic
      peptide 1-28 (ANP1-28) in rats. After various doses of ANP1-28 administration the
      CRF-LI significantly increased in the hypothalamus, the hippocampus and the
      frontal cortex. In the amygdala, ANP caused a marked but nonsignificant CRF-LI
      enhancement. In the basal forebrain, the CRF-LI decreased. These results suggest
      that ANP1-28 may moderate activation of the CRF-ergic system in the brain which
      could be related to the neuroendocrine and behavioral action.

PMID- 8876665
TI  - Salivary monoamine oxidase A and B inhibitory activities correlate with stress.
AB  - MAO A and B inhibitory activities were determined, for the first time, in saliva
      samples. Saliva was collected on 4 occasions from 11 normal subjects (students)
      before and after delivering an important assessed oral presentation, a
      naturalistic stress inducing procedure. The first sample was collected 30 minutes
      before the presentation and 3 more within 40 minutes of finishing the
      presentation. At each collection a mood adjective checklist was completed. Mean
      MAO A inhibitory activity correlated with mean MAO B inhibitory activity (r =
      0.872, p < 0.001, n = 11). Within subject analysis revealed a positive
      correlation between MAO A and B inhibitory activity and stress (r = 0.400, p <
      0.01, n = 44 and r = 0.255, NS, n = 38 respectively). Mean MAO A and B inhibitory
      activity correlated with mean stress (r = 0.535, NS, n = 11 and r = 0.673, p <
      0.05, n = 11 respectively). Peak MAO A and B inhibitory activities correlated
      with peak stress (r = 0.636, p < 0.05, n = 11 and r = 0.754, p < 0.01, n = 11,
      respectively). Salivary MAO A and B inhibitory activities were independent of
      salivary flow rate. We conclude that measurement of MAO A and B inhibitory
      activities in saliva is preferable to traditional urinary measures as sampling is
      less invasive and also supports a clear relationship to stress in normal
      individuals.

PMID- 8876666
TI  - Overexpression of bovine growth hormone in transgenic mice is associated with
      changes in hepatic insulin receptors and in their kinase activity.
AB  - Transgenic mice expressing a hybrid gene produced by linking the promoter
      regulatory region of phosphoenolpyruvate carboxykinase (PEPCK) gene to the bovine
      growth hormone (bGH) gene, were used to investigate the effects of GH on insulin
      binding and insulin dependent tyrosine kinase activity of hepatic insulin
      receptors. Transgenic mice had normal levels of blood glucose, despite
      hyperinsulinemia, indicating that these animals were insulin resistant. The
      number of insulin receptors in the liver of transgenic mice was significantly
      decreased in both the particulate fraction (25%) and the solubilized membranes
      (40%) indicating that expressed (functional) and non-expressed (cryptic)
      receptors were affected. Scatchard analysis of competitive binding curves for
      insulin indicated that the affinity of the receptor did not differ between
      transgenic and normal mice. Insulin dependent tyrosine kinase activity in insulin
      receptors partially purified by wheat germ agglutin (WGA) agarose chromatography
      from solubilized liver membranes, was measured. The stimulatory action of insulin
      on phosphorylation of the synthetic substrate (a copolymer Glu-Tyr, 4:1) was
      increased 100% in transgenic, as compared to normal mice, using the same binding
      activity. Since transgenic mice are hyperinsulinemic, it is likely that the
      decreased insulin binding in this group reflects down regulation of the expressed
      and non-expressed insulin receptors, and the increased kinase activity represents
      a compensatory mechanism. We conclude that alterations in the insulin receptor
      number and in the tyrosine kinase activity develop in response to changes in
      insulin levels. Thus, insulin resistance detected in the liver of transgenic mice
      overexpressing GH may be due to post receptor defects.

PMID- 8876667
TI  - Inhibition by bosentan, an endothelin antagonist, of the hypersensitivity to Ca2+
      channel activator evoked by salt-loading in basilar artery of stroke-prone
      spontaneously hypertensive rats.
AB  - High salt diet dramatically decreases the life time of spontaneously hypertensive
      stroke-prone rats (SHRSP). This has been related to an increase in the incidence
      of stroke. We have investigated the influence of high salt diet on the reactivity
      to the Ca2+ channel activator Bay K 8644 of basilar artery isolated from SHRSP.
      The results show that the sensitivity of basilar artery to Bay K 8644 was
      increased by salt load and that this hypersensitivity was blunted by bosentan, an
      ETA/ETB antagonist.

PMID- 8876668
TI  - Interactions between cAMP- and cGMP-dependent protein kinase inhibitors and
      phosphodiesterase IV inhibitors on arachidonate release from human monocytes.
AB  - The effects of specific inhibitors of cAMP-dependent protein kinase (PKA) and
      cGMP-dependent protein kinase (PKG) on the inhibitory activity of
      phosphodiesterase (PDE) type IV inhibitors and of the cell permeable analogue of
      cAMP, db-cAMP, were investigated on fMLP-induced arachidonate release from human
      monocytes. When monocytes were preincubated with the combined PKA/PKG inhibitor
      H8 (10(-6) to 10(-4) M) or the selective PKG inhibitor Rp-8-cpt-cGMPs (10(-6) to
      10(-4) M) a concentration-dependent reduction of the inhibitory effect of db-cAMP
      (10(-3) M), rolipram (10(-5) M) and Ro 20-1724 (10(-5) M) was noted. When
      monocytes were preincubated with the selective PKA inhibitor H89 (10(-6) to 10(
      4) M), only a small inhibition of the effect of db-cAMP and no inhibition of the
      effects of rolipram and Ro 20-1724 were observed. The present data indicate that
      db-cAMP and PDE IV inhibitors elicit an in vitro anti-inflammatory activity by a
      PKA-independent mechanism, which do not appear to be mainly mediated via the PKG
      activation.

PMID- 8876669
TI  - Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and
      adjacent non-neoplastic brain.
AB  - Nucleotide excision repair (NER) is an ordered process in nonmalignant cells, in
      both human and nonhuman systems. We previously reported that in human brain there
      is discordant mRNA expression of excision repair cross-complementing (ERCC) 1 and
      ERCC2 in malignant tissues, concurrent with excellent concordance of these genes
      in nonmalignant tissues from the same patients. Here we have extended these
      studies to compare low-grade tumors to high-grade tumors and to include ERCC3
      (which links DNA repair with DNA transcription) and ERCC6 (which is essential for
      gene-specific repair). Glial tumor and adjacent normal brain specimens from 19
      individuals were studied. Paired malignant and nonmalignant tissues were obtained
      from 12 of these patients. For ERCC3, there was excellent concordance of mRNA
      expression between malignant and nonmalignant tissues from the same individuals
      (P = 0.003). For ERCC6, no concordance was observed (P = 0.314). Tumor tissue
      from patients with high-grade gliomas exhibited marked discordance of mRNA
      expression patterns in situations in which good concordance was observed in tumor
      tissue from low-grade gliomas. We previously established that malignant brain
      tumors show increased disorder of genes in the NER process, as compared with
      nonmalignant tissues. These data suggest that increasing disorder in the NER
      process may occur as cells move from low-grade to high-grade malignancy.

PMID- 8876670
TI  - Changes in jun N-terminal kinase activation by stress during aging of cultured
      normal human fibroblasts.
AB  - The molecular changes associated with the aging process include the reduced
      activity of transcription factors (such as AP-1) and an impaired response to
      stress, which has been well documented in the case of the heat-shock (HS)
      response. Using human diploid fibroblasts of early and late passages as an in
      vitro model for aging, we elucidated changes in the activation of jun N-terminal
      kinases (JNKs), which play an important role in the mammalian stress response. We
      found that early-passage cells exhibited a greater degree of JNK activation in
      response to HS and ultraviolet (UV) C light treatments than did late-passage
      cells. Decreased JNK activation was dependent on the number of passages but was
      not affected by varying doses of UV irradiation. Analysis of protein kinase A,
      mitogen-activated protein kinase, and src-related tyrosine kinases revealed no
      decreased activities in aged cells, indicating a selective rather than
      generalized decrease in kinase activities during aging. A further understanding
      of this impaired activation of JNK may provide insights into the mechanisms of
      stress response and cellular aging.

PMID- 8876671
TI  - Protection against malignant conversion in SENCAR mouse skin by all trans
      retinoic acid: inhibition of the ras p21-processing enzyme farnesyltransferase
      and Ha-ras p21 membrane localization.
AB  - Many studies have shown that all trans retinoic acid (RA) exhibits significant
      protective effects against mouse skin tumor promotion and spontaneous as well as
      enhanced malignant conversion. In a recently completed study, we showed that
      under treatments in which papillomas on SENCAR mouse skin are induced at low and
      high probabilities to convert to malignant carcinomas, RA affords significant
      protection against both tumor promotion and subsequent malignant conversion. More
      than 95% of these mouse skin papillomas and carcinomas have been shown to contain
      point mutation at the 61 codon of Ha-ras oncogene. The ras oncogene encodes a p21
      protein that, in its mutated form, transforms mammalian cells only when p21 is at
      the inner surface of the plasma membrane, by a series of enzymatic reactions in
      which the initial step is catalyzed by farnesyltransferase (FTase). In this
      study, we assessed whether the protective effect of RA against malignant
      conversion involves the inhibition of ras p21 processing in those tumors that
      contain the activated ras oncogene. The FTase activity and the levels of
      cytosolic and membrane-bound Ha-ras p21 were determined in all papillomas and
      carcinomas obtained from acetone- or RA-treated animals. No matter how the data
      were analyzed and what comparisons were considered, in all the protocols used,
      compared with controls, papillomas and carcinomas obtained from RA-treated groups
      showed significantly decreased (P < 0.01-0.001) FTase activity. Furthermore, the
      tissue samples from RA-treated groups in different protocols also showed
      significantly diminished membrane localization of Ha-ras p21, with a concomitant
      increase in cytosolic Ha-ras p21 levels. The analysis of these data also showed
      that in all the protocols used, the increased FTase activity and membrane
      localization of Ha-ras p21 were associated with the induction of papillomas and
      their subsequent malignant conversion to squamous cell carcinomas. Taken
      together, these results indicate a strong correlation between the inhibition of
      ras p21 farnesylation because of a decrease in FTase activity by RA and its
      protective effect against malignant conversion of papillomas to carcinomas. Based
      on the results of this study, it is tempting to suggest that clinical trials
      evaluating the preventive or therapeutic potential of retinoids may be directed
      more toward those clinical malignancies that are known to contain the activated
      ras oncogene.

PMID- 8876672
TI  - ras downregulation of protein kinase C mRNA in C3H 10T1/2 fibroblasts.
AB  - C3H 10T1/2 fibroblasts transformed by oncogenic ras have lower levels of protein
      kinase C (PKC) activity and protein. It was previously suggested that elevated
      levels of diacylglycerol in ras-transformed fibroblasts lead to activation
      induced proteolysis of cellular PKC. We found that stable expression of T24ras in
      C3H 10T1/2 fibroblasts resulted in a significant decrease in levels of PKC alpha
      and PKC epsilon mRNA. Using C3H 10T1/2 cell lines in which the levels of
      activated ras can be exogenously regulated (by addition of zinc to induce the
      expression of a metallothionein-promoted human Ha-ras oncogene), we examined the
      temporal dependence of oncogenic ras expression on PKC downregulation. In these
      cells, downregulation of PKC protein and activity was induced but was not
      preceded by activation of PKC. The downregulation of PKC levels correlated with
      the appearance of a highly transformed morphology and was seen only at high
      levels of ras expression. In the inducible cells, the decrease in levels of PKC
      alpha mRNA had the same dependence on the levels of ras expression as did protein
      downregulation. These experiments provide evidence that downregulation of PKC
      protein levels by expression of oncogenic Ha-ras in C3H 10T1/2 fibroblasts is
      primarily due to altered transcriptional regulation. Because the downregulation
      of PKC was coupled with the onset of morphological transformation, the data
      suggest that this downregulation is involved in or facilitates the maintenance of
      a ras-transformed phenotype in C3H 10T1/2 fibroblasts.

PMID- 8876673
TI  - Restoration of responsiveness to phorbol ester by reconstitution of a functional
      Na/K/Cl cotransporter in cotransporter-deficient BALB/c 3T3 cells.
AB  - Previous studies in this laboratory have implicated the membrane transport
      protein Na/K/Cl cotransporter (NKCC1) as an important component of the signaling
      pathways activated by phorbol esters in BALB/c 3T3 cells. The NKCC1 protein
      functions as a Na/K/Cl cotransporter in BALB/c 3T3 cells and many other cell
      types. Loss of NKCC1 function has been associated with loss of mitogenic
      responsiveness to phorbol ester. Here we report that expression of a cloned NKCC1
      cDNA fused to a tetracycline-regulated promoter in BALB/c 3T3 cells deficient in
      Na/K/Cl cotransport activity (clone E12a cells) restored cotransport function.
      Compared with parental cotransport-deficient cells, transfected clones expressing
      the exogenous NKCC1 gene responded like typical BALB/c 3T3 cells to 12-O
      tetradecanoylphorbol-13-acetate: loop diuretic-sensitive 86Rb+ flux was
      inhibited, cell volume was decreased, and cell growth was stimulated. These
      results support our previous conclusion that the loss of responsiveness of E12a
      cells to phorbol ester is caused by mutation of the endogenous NKCC1 gene.

PMID- 8876674
TI  - Large deletions at the HPRT locus associated with the mutator phenotype in a
      Bloom's syndrome lymphoblastoid cell line.
AB  - Bloom's syndrome (BS) is an autosomal recessive disorder with a high cancer
      incidence. BS cells exhibit increased chromosomal instability and sister
      chromatid exchange. The rate of spontaneous mutation at the locus encoding
      hypoxanthine phosphoribosyltransferase (HPRT) in a lymphoblastoid cell line
      derived from a BS patient, GM3403, was 1.39 x 10(-6) mutations/cell/generation,
      whereas that in TK6, a lymphoblastoid cell line derived from an individual who is
      not suffering from BS, was 1.75 x 10(-8) mutations/cell/generation. Molecular
      analysis of the HPRT gene in mutant clones by multiplex polymerase chain reaction
      revealed that 83.3% of the spontaneous mutants from GM3403 cells contained
      deletions at the HPRT locus, whereas 30.8% of mutants from TK6 cells had
      deletions. Approximately half of the BS mutants had lost the entire gene. Some
      mutant clones of GM3403 had also lost markers near the HPRT locus, although no
      mutant clones from TK6 cells had lost these markers. These results indicate that
      the mutator phenotype of BS cells is mainly due to an increase in large DNA
      alterations, reflecting the remarkable genomic instability that could be
      responsible for cancer proneness in this disease.

PMID- 8876675
TI  - Base analog N6-hydroxylaminopurine mutagenesis in Escherichia coli: genetic
      control and molecular specificity.
AB  - We have studied the molecular specificity of the base analog N6
      hydroxylaminopurine (HAP) in the E. coli lacI gene, as well as the effects of
      mutations in DNA repair and replication genes on HAP mutagenesis. HAP induced
      base substitutions of the two transition types (A . T-->G . C and G . C-->A . T)
      at equal frequency. This bi-directional transition specificity is consistent with
      in vitro primer extension experiments with the Klenow fragment of DNA polymerase
      I in which we observed that either dTTP or dCTP were incorporated opposite HAP in
      an oligonucleotide template. The spectrum of HAP-induced transitions was
      different from the spontaneous transitions in either a wild-type or a mismatch
      repair-defective (mutL) strain. Mutations in genes controlling excision repair,
      exonucleolytic proofreading, mismatch correction, error-prone (SOS) repair and 8
      oxo-guanine repair did not affect HAP-induced mutagenesis substantially. However,
      an extensive deletion of several genes in the uvrB-bio region conferred
      supersensitivity to the lethal and mutagenic effects of HAP, perhaps due to an
      effect on HAP metabolism. dnaE antimutator alleles reduced HAP-forward
      mutagenicity in allele-specific manner: dnaE911 reduced it several fold, while
      dnaE915 abolished it almost completely. The results obtained are consistent with
      the idea that HAP is mutagenic in E. coli via a pathway generating replication
      errors.

PMID- 8876676
TI  - In vivo dosimetry of ethylene oxide and propylene oxide in the cynomolgus monkey.
AB  - In mammals, including the cynomolgus monkey, a striking difference between the
      potencies of ethylene oxide (EO)* and propylene oxide (PO) with respect to
      induction of certain clastogenic effects has previously been observed. In order
      to clarify to what extent such differences can be ascribed to a difference in
      detoxification rate, cynomolgus monkeys were administered an equimolar mixture of
      the two epoxides at two dose levels, and the blood doses were determined by
      measurement of the degree of alkylation of N-terminal valines in hemoglobin (Hb).
      For the highest exposure a saturation in the detoxification of PO was evident
      from a marked increase in adduct level. At the lower exposure, the dose in blood
      resulting from exposure to PO was about one fourth of that from EO. Although
      playing a great role, differences in detoxification rate, therefore, cannot fully
      account for the much lower clastogenic potency of PO, which has been found in
      earlier studies. Furthermore, the determination of doses in blood gives data on
      relationship between in vivo dose and exposure dose (accounting for
      detoxification), with relevance for risk estimation.

PMID- 8876677
TI  - Effects of reactive oxygen species (ROS) modulators, TEMPOL and catalase, on
      methoxyacetaldehyde (MALD) -induced chromosome aberrations in Chinese hamster
      ovary (CHO)-AS52 cells.
AB  - Methoxyacetaldehyde (MALD), a metabolite of 2-methoxyethanol, has been shown to
      be clastogenic and mutagenic in CHO-AS52 cells. PCR-based-deletion screening of
      MALD induced CHO-AS52 mutants indicates that MALD induces large deletion
      mutation. Since MALD has an aldehyde as its reactive functional group, it can
      react with aldehyde oxidase to produce superoxide. The generation of these
      reactive oxygen species (superoxide, hydrogen peroxide and hydroxyl radical) may
      be the mechanism for genotoxicity of MALD. In the present study, TEMPOL and
      catalase which are ROS modulators were used to study the effects on MALD-induced
      chromosome damage in CHO-AS52 cells. The results showed that neither TEMPOL nor
      catalase can protect cells from MALD-induced chromosome aberrations. Therefore,
      the generation of reactive oxygen species may not be the primary mechanism of
      action of MALD.

PMID- 8876678
TI  - Distinct difference in relative biological effectiveness of 252Cf neutrons for
      the induction of mitotic crossing over and intragenic reversion of the white
      ivory allele in Drosophila melanogaster.
AB  - The relative biological effectiveness (RBE) of 252Cf neutrons was determined for
      two different types of somatic mutations, i.e., loss heterozygosity for wing-hair
      mutations and reversion of the mutant white-ivory eye-color, in Drosophila
      melanogaster. Loss of heterozygosity for wing-hair mutations results
      predominantly from mitotic crossing over induced in wing anlage cells of larvae,
      while the reverse mutation of eye color is due to an intragenic structural change
      in the white locus on the X-chromosome. For a quantitative comparison of RBE
      values for these events, we have constructed a combined mutation assay system so
      that induced mutant wing-hair clones as well as revertant eye-color clones can be
      detected simultaneously in the same individuals. Larvae were irradiated at the
      age of 80 +/- 4 h post-oviposition with 252Cf neutrons or 137Cs gamma-rays, and
      male adult flies were examined under the microscope for the presence of the two
      types of clonal mosaic spots appearing. The induction of wing-hair spots per dose
      unit was much greater for 252Cf neutrons than for 137Cs gamma-rays, whereas the
      frequencies of eye-color reversion were similar for neutrons and gamma-rays. The
      estimated RBE values of neutrons were 8.5 and 1.2 for the induction of mutant
      wing-hair spots and revertant eye-color spots, respectively. These results
      indicate that the RBE of neutrons is much greater for mitotic crossing over in
      comparison to the intragenic white-ivory reversion events. Possible causes for
      the difference in RBE are discussed.

PMID- 8876679
TI  - The selection-induced His+ reversion in Salmonella typhimurium.
AB  - It was previously shown that spontaneous reversion to His+ of the allele hisG46
      Salmonella typhimurium occurs under the influence of histidine starvation. No pre
      existing His+ revertants arisen in rich medium were observed. We have now shown
      that the pre-existing His+ revertants are seen under increased cell concentration
      (10(10) cells/ml). At the same time, it was established that the selection
      induced His+ reversion events of hisG46 begin to occur after 2-3 h of incubation
      on histidine starvation plates, and this process continues for about 4 days. In
      parallel, considerable DNA synthesis was observed for the initial hours of
      starvation. Chloramphenicol and novobiocin inhibited this DNA synthesis, whereas
      the addition of trace of histidine as well as novobiocin produced the delay of
      adaptive His+ reversion. It was found that adaptive reversion of hisG46 is recA
      independent, although it requires some activity of RecA on the mucAB genetic
      background. Based on these data, we suggest that the cause of adaptive His+
      reversion is the DNA replication operating under histidine starvation. Using a
      number of mutation models, we showed that histidine starvation did not increase
      the general mutation rate. It was also demonstrated that intragenic revertants
      and extragenic ochre suppressors of the allele hisG428 arise under the influence
      of histidine deprivation.

PMID- 8876680
TI  - A novel lacI transgenic mutation-detection system and its application to
      establish baseline mutation frequencies in the scid mouse.
AB  - To assess DNA mutations in vivo, we have established a new transgenic mouse line,
      BC-1, carrying a lacI target gene for mutation detection within a bacteriophage
      shuttle-vector. The lacI gene was positioned within sequences derived from a
      rearranged murine immunoglobulin gene locus, a feature that distinguishes the BC
      1 transgene from other shuttle vector systems. As mutations in lacI transgenes
      likely reflect mutations occurring throughout the genome, these systems have been
      successfully used to investigate spontaneous and induced mutations in a variety
      of tissues. An important additional application of the transgenic systems is the
      characterization of lacI mutations occurring in murine strains having specific
      DNA repair defects. For this study, scid (severe combined immunodeficiency) mice
      were selected as animals with this mutation have a defect in double-strand DNA
      break repair. To determine what impact the scid mutation might have on
      spontaneous mutation frequencies within DNA recovered from various tissues, these
      mice were crossed with the BC-1 line. Interestingly, mutation frequencies within
      BC-1/scid mouse DNA were not significantly different from those of BC-1 control
      mice. Furthermore, spontaneous lacI mutations obtained from BC-1 and from BC
      1/scid liver DNA were similar in spectrum. As spontaneous BC-1 liver mutations
      were similar to those reported previously for other lacI systems, such as the Big
      Blue transgenic line, this suggested that the nature of the DNA sequences
      flanking the reporter gene did not modify lacI mutation rate or character.

PMID- 8876681
TI  - Radiosensitivity of haplont yeast cells irradiated with sparsely and densely
      ionizing radiations.
AB  - Five haploid and three diploid yeast strains of various species (Yarrowia
      lipolytica, Pichia pinus and Pichia guilliermondii) were irradiated with alpha
      particles from 239Pu and gamma-rays from 137Cs or 60Co in the stationary phase of
      growth. A common feature of these species is that they exhibit a haploid state as
      a normal vegetative state in natural conditions. It was shown that the transition
      from the haploid to the diploid state is not accompanied by increased
      radioresistance, and diploid strains were unable to perform liquid-holding
      recovery. The absence of diploid-specific recovery in diploid strains was also
      supported by the fact that the RBE of alpha-particles was almost identical for
      haploid and the corresponding diploid strains being much smaller than that
      observed in typical wild-type diploid strains capable of diploid-specific
      recovery. The results suggest that haplont yeast may have evolved to diplont
      yeast via the development of a specific repair system conferring specific
      resistance in the diploid state.

PMID- 8876682
TI  - Modulating factors of individual sensitivity to diepoxybutane: sister chromatid
      exchanges induced in vitro in human lymphocytes.
AB  - Spontaneous and diepoxybutane (DEB)-induced sister chromatid exchanges (SCEs)
      were examined in cultured peripheral lymphocytes (PBL) from 122 healthy donors.
      SCE-inducing activity under defined experimental conditions and individual
      sensitivity to genotoxic stress were assessed. SCE means distribution appeared
      asymmetrical, identifying about 22% of subjects characterized by a 'high
      respondent' phenotype with more than 111 SCEs/cell. Confounding factors, such as
      smoking habit, wine and coffee consumption, work activity and hematological
      factors, showed a limited capacity to affect individual SCE responsiveness,
      however hemoglobin and uric acid seemed to antagonize DEB genotoxicity.

PMID- 8876683
TI  - Oxygen is not required for degradation of DNA by glutathione and Cu(II).
AB  - Previous studies by others have shown that thiols, such as glutathione, cause
      cleavage of DNA in the presence of Cu(II) ions and that the hydroxyl radical
      derived from molecular oxygen is the major cleaving species. In this paper, we
      present several lines of evidence that strongly suggest that molecular oxygen is
      not essential for DNA cleavage and that thiyl radicals may also be involved.
      Indirect evidence is presented to indicate that glutathione may substitute oxygen
      as an electron acceptor. In addition, DNA degradation occurs to a significant
      extent under anaerobic conditions and no inhibition of single-strand cleavage of
      supercoiled plasmid DNA is seen in the presence of superoxide dismutase and
      catalase. In view of the ubiquitous presence of glutathione, these results could
      be of interest under certain diseased conditions where copper concentrations are
      elevated.

PMID- 8876684
TI  - Lymphocyte mutant frequency in relation to DNA adduct formation in rats treated
      with tumorigenic doses of the mammary gland carcinogen 7,12
      dimethylbenz[a]anthracene.
AB  - The ability of the rat lymphocyte hprt assay to detect tissue-specific
      carcinogens was evaluated using 7,12-dimethylbenz[a]anthracene (DMBA)
      administered under conditions that result in mammary gland tumors. Fifty-day-old
      female Sprague-Dawley rats were given single doses of 5 and 20 mg/kg DMBA by
      gavage, and the frequency of 6-thioguanine-resistant (TGr) T-lymphocytes was
      measured over a period of 21 weeks. A time- and dose-dependent increase in mutant
      frequency was found, with a maximum frequency found 9-15 weeks after treatment
      with 20 mg/kg of DMBA. Rats were also dosed with 1, 2.5, 5, 10, 15 and 20 mg/kg
      of DMBA and assayed for TGr mutant frequency 10 weeks after treatment. A
      significant linear dose-response was found, with all the DMBA doses resulting in
      significant increases in mutant frequency. To determine whether or not DMBA
      induced mutants in rat lymphocytes reflected the DNA damage in the target tissue,
      rats were treated with 5 and 20 mg/kg of DMBA and spleen lymphocytes and mammary
      gland tissue were assayed for DNA adduct formation 1, 3 and 7 days later. A
      similar pattern of 32P- postlabeled adducts, involving both dG and dA
      nucleotides, was found in DNA from both the target tissue and the surrogate
      lymphocytes. Adduct formation was dose responsive in both tissues, with a 2.3- to
      4-fold higher concentration in mammary gland as compared with lymphocytes. These
      results indicate that the rat lymphocyte hprt assay is sensitive to a mammary
      gland carcinogen and that similar types of DNA adducts are associated with both
      the lymphocyte mutants and the mammary gland tumors induced by DMBA.

PMID- 8876685
TI  - Radiosensitivity of blood lymphocytes from basocellular carcinoma patients, as
      detected by the micronucleus assay.
AB  - Cytogenetic techniques, the micronucleus (MN) assay, in particular, have been
      widely used in population monitoring, biological dosimetry and early detection of
      groups susceptible to cancer. Individuals respond differently to several
      environmental agents. The efficiency of the cellular repair mechanisms would be
      responsible, at least to some extent, for individual differences in sensitivity
      to neoplasia. In order to determine the sensitivity of cancer patients to
      ionizing radiation, blood cultures from untreated individuals with basocellular
      carcinoma, young healthy subjects and older healthy subjects, were irradiated in
      vitro with 60Co at doses ranging from 0 to 500 cGy and submitted to the cyto-B
      micronucleus assay; the frequency of cells and distribution of MN and dose
      response relationships were analyzed. Results showed that cancer patients had a
      lower frequency of cells with spontaneous MN than older healthy subjects. The
      frequency of micronucleated cells was not different in patients and healthy
      subjects, but not the distribution of MN per radiation dose: for the carcinoma
      group, while the proportion of cells with one MN decreases drastically, the
      proportion of the cells with two or more MN increases with the same intensity.
      Our results show that the proportion of damaged cells is similar in patients with
      basocellular carcinoma and healthy subjects, but the magnitude of radiation
      induced lesion is greater in the cancer patients.

PMID- 8876686
TI  - Similarity of in vivo somatic mutations at an autosomal adenine
      phosphoribosyltransferase locus between T- and B-cells in human peripheral blood.
AB  - In vivo somatic mutations have been detected at several human loci by using
      clonal cultures of peripheral blood T-cells. It has not been fully understood
      whether or not the somatic mutations in T-cells are similar to those of other
      cell types. To address this issue, we cloned, from human peripheral blood, T- and
      B-cells with mutations at an autosomal adenine phosphoribosyltransferase (APRT)
      locus. For the efficient detection of somatic mutations at the APRT locus, a
      blood sample from a human individual heterozygous for germline APRT deficiency
      was used. T- and B-cells deficient in APRT enzyme activity were cloned from
      peripheral blood mononuclear cells using a selecting agent, 2,6-diaminopurine.
      The APRT-deficient mutant frequencies were on the order of 10(-4) in both T- and
      B-cells. The single-strand conformation polymorphism analysis of the APRT DNA of
      mutant B-cell clones suggested that the molecular mechanisms leading to the APRT
      deficiency in B-cells were similar to those in T-cells. Our observations suggest
      that both the frequency and the mode of in vivo somatic mutations occurring
      spontaneously at general autosomal loci in B-cells are similar to those in T
      cells.

PMID- 8876687
TI  - Effect of hydroxyurea and normal plasma on DNA synthesis in lymphocytes from
      Fanconi anemia patients.
AB  - Fanconi anemia (FA) is characterized at the cellular level by a high frequency of
      spontaneous chromosomal aberrations; crosslinking agents cause an abnormal
      increase in the frequency of chromosomal damage, and semiconservative DNA
      synthesis is severely inhibited. Deoxyribonucleotides are needed in both
      semiconservative and repair DNA synthesis. To investigate the involvement of
      deoxyribonucleotide pools in the inhibition of DNA synthesis in FA, we evaluated
      the effect on FA lymphocytes of hydroxyurea (HU), an inhibitor of ribonucleotide
      reductase which is known to alter the intracellular levels of
      deoxyribonucleotides. To achieve this goal, lymphocyte cultures of 4 FA patients
      and 4 normal individuals were used. Cultures were treated with HU and/or
      mitomycin C and normal human plasma. All cultures were processed to detect the
      number of DNA synthesizing nuclei by autoradiography. Scoring of 2000 nuclei for
      each kind of culture every 6 h in the last 24 h of incubation showed that, in
      long incubation periods, DNA synthesis in FA is largely inhibited by HU and this
      hypersensitivity may be partially decreased by addition of normal human plasma.
      It is known that recovery from damage induced by HU involves several enzymes such
      as flavin oxido-reductase, superoxide dismutase and catalase which are involved
      in the production or scavenging of O2 radicals; FA cells are deficient in the
      detoxification of oxygen and this could explain the response of FA cells to HU.

PMID- 8876688
TI  - Induction of chromosomal aberrations in cultured human fibroblasts by inorganic
      and organic arsenic compounds and the different roles of glutathione in such
      induction.
AB  - Clastogenic effects of a variety of arsenic compounds were examined on cultured
      human fibroblasts. The following compounds were tested: inorganic arsenicals
      (arsenite and arsenate), the major metabolites of inorganic arsenicals in human
      and experimental animals [methylarsonic acid (MAA), dimethylarsinic acid (DMAA)
      and trimethylarsine oxide (TMAO)], and water-soluble organoarsenic derivatives
      [2', 3'-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-beta-D-riboside (arsenosugar),
      arsenocholine, arsenobetaine and tetramethylarsonium iodide] found in marine
      organisms. Arsenic compounds induced mainly chromatid gaps and chromatid breaks.
      The rank order of compounds in terms of clastogenic potency was arsenite >
      arsenate > DMAA > MAA > TMAO. DMAA was very potent and caused chromosome
      pulverizations in most metaphases when present at doses higher than 7 x 10(-3) M.
      Arsenosugar, arsenocholine, arsenobetaine and tetramethylarsonium iodide were
      less effective. Depletion of cellular glutathione (GSH) with L-buthionine-SR
      sulfoximine (BSO), increased the incidence of chromosomal aberrations induced by
      arsenite, arsenate and MAA, and markedly suppressed the clastogenic effects of
      DMAA. DMAA was highly clastogenic even in GSH-depleted cells when the cells were
      incubated with DMAA in the presence of GSH (5 and 10 mM). These results suggest
      that GSH might play a role in protecting cells against the clastogenic effects of
      arsenite, arsenate and MAA. GSH might be involved in the expression of
      clastogenic actions of DMAA.

PMID- 8876689
TI  - Adaptive and synergistic effects of a low-dose ENU pretreatment on the frequency
      of chromosomal aberrations induced by a challenge dose of ENU in human peripheral
      blood lymphocytes in vitro.
AB  - N-Ethyl-N-nitrosourea (ENU) is an alkylating agent whose mutagenic and
      carcinogenic potential has been extensively studied but its ability to induce
      cytogenetic adaptive responses in normal human cells has not been investigated so
      far. The aim of our present experiments was to study the effect of a pretreatment
      with a low concentration of ENU (2 x 10(-5) M) on the frequency of chromosomal
      aberrations induced by a subsequent 50 times higher concentration of ENU (10(-3)
      M) in human lymphocytes isolated from buffy coats of 4 donors. Two different
      inter treatment times and three harvesting times were applied to the lymphocytes
      from each donor. A cytogenetic adaptive response was shown by the lymphocytes of
      one donor only when the time span between the low adapting and the higher
      challenging concentration was 4 h. The other three donors did not respond with
      significant differences in the yield of cells with aberrations. The complex
      interaction between the ENU-induced multiple primary DNA lesions and various DNA
      repair mechanisms as well as the influence of cell cycle effects on the induction
      of clastogenic adaptive response are discussed.

PMID- 8876690
TI  - A role for apoptosis in the toxicity and mutagenicity of bleomycin in AHH-1 tk+/-
      human lymphoblastoid cells.
AB  - The chromosomal mutagen, bleomycin, is also noted for its toxic properties,
      although the mechanism of cell death is not fully understood. In order to
      determine if cell death occurred by apoptosis or necrosis, AHH-1 tk+/- cells were
      exposed to bleomycin and the percentage of viable, apoptotic and necrotic cells
      quantified by flow cytometry. Logistic regression analysis indicated that the
      primary manner of cell death was through the apoptosis pathways, that apoptosis
      was delayed, and that apoptosis was accompanied by an arrest in the G2 phase of
      the cell cycle. Once apoptosis was established as a mechanism for cell death, the
      efficiency with which these pathways removed damaged cells from the population
      was evaluated with the use of specific-locus mutation assays (tk and hprt) as
      indicators of cells with DNA damage that maintained viability and clonogenicity.
      Linear regression analysis detected a significant, concentration-dependent
      increase in the numbers of TFTr clones with the slow-growth phenotype. This
      suggests that a proportion of cells with bleomycin-induced DNA damage did not
      undergo cell death by apoptosis and that apoptosis, a mechanism for the
      destruction of damaged cells, is not fully efficient in the AHH-1 tk +/- cell
      line.

PMID- 8876691
TI  - The estimation of in vivo mutation rate and frequency from samples of human
      lymphocytes.
AB  - In vivo mutation assays usually involve enumeration of mutant cells in samples
      drawn from individuals or populations, and inferences concerning quantitative
      aspects of mutation are made from the results. Individual cells within the
      samples may show clonal relationships with each other. For populations of
      constant size, which do not obey Luria-Delbruck kinetics, mutation frequency
      should be calculated from the number of mutant cells and not from the number of
      mutant clones. The change in mutation frequency/unit time provides the best
      estimate of the mutation rate, which for human T lymphocytes is approx. 2.0 x 10(
      9) mutations/cell/day, a rate higher than that explicable by proliferation alone.
      Since lymphocyte populations in vivo contain uncommon large clones, the
      statistics of rare events results in all measured mutant frequencies for
      individuals being affected by discontinuous variation. The presence or absence of
      a large mutant clone in an individual results in the measured MF being either a
      large overestimate of the population MF in a minority of individuals or a small
      underestimate in the majority of individuals. An adjusted mutation frequency can
      be calculated to eliminate this source of variation but this is rarely necessary.

PMID- 8876692
TI  - Involvement of antipain-sensitive protease activity in the interferon-beta
      induced UV-refractoriness of Cockayne syndrome fibroblasts.
AB  - Fibroblast cells obtained from two siblings and a female patient with Cockayne
      syndrome (CS), when pretreated with human interferon (HuIFN)-beta prior to
      irradiation with UV light (254 nm wavelength), exhibited transiently induced
      fibrinolytic protease activity immediately after the irradiation in association
      with increased refractoriness to UV cell-killing. A protease inhibitor, antipain,
      inhibited the induction of protease activity in lysates of the CS fibroblasts
      from these 3 cases after the combination of HuIFN-beta pretreatment and UV
      irradiation, whereas elastatinal and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)
      inhibited the activity less than antipain did. Antipain also suppressed the
      increase in UV-refractoriness of HuIFN-beta-pretreated CS fibroblasts, as
      revealed by culturing cells for 24 h in medium containing the inhibitor
      immediately after UV exposure and thereafter evaluating the ability of colony
      formation by the cells. Thus, an antipain-sensitive protease may be involved in
      the UV-refractoriness induced by HuIFN-beta in CS fibroblast strains.

PMID- 8876693
TI  - Spontaneous and mitomycin-C-induced micronuclei in lymphocytes from subjects
      affected by Turner's syndrome.
AB  - Peripheral blood lymphocytes from 15 subjects affected by Turner's syndrome (TS)
      and aged between 2 and 24 years (mean age 10.40 +/- 6.25) were tested to evaluate
      the spontaneous and Mitomycin-C-induced (MMC) micronucleus (MN) frequency. A
      group of 15 healthy subjects, in the same range of age (mean age 14.67 +/- 8.30),
      was also tested as control. As expected, statistically significant differences
      between spontaneous and MMC-induced MN were found either in TS and in healthy
      subjects. Unexpectedly, when the two groups of donors were compared, TS subjects
      showed a lower spontaneous and MMC-induced MN frequency, in comparison with
      healthy subjects. Cell proliferation kinetic and cytotoxicity were also measured
      applying the cytokinesis-block proliferation index (CBPI): the results show that
      MMC, at the employed concentration, does not induce cell cycle delay both in
      healthy and in TS donors. Whereas, when CBPI from TS and healthy donors were
      compared, a faster proliferation was found in TS patients in both untreated and
      MMC-treated cultures.

PMID- 8876694
TI  - Comparison of the frequency of T-cell receptor mutants and thioguanine resistance
      induced by X-rays and ethylnitrosourea in cultured human blood T-lymphocytes.
AB  - We have investigated two assays for measuring the induction of mutations using
      human T-lymphocytes isolated from leukocyte residue buffy coats obtained from
      normal donors. Variant cell frequency of T-cells defective in the T-cell receptor
      (TCR) gene expression was measured using a 2-color flow cytometry, and 6
      thioguanine-resistant (TGr) cells were determined using a cloning technique at
      the HPRT gene after treatment with 250 kVp X-rays or ethylnitrosourea (ENU). The
      frequencies of TCR mutant cells as well as those of TGr cells increased with
      increasing doses of X-rays or concentrations of ENU studied. For TCR mutants, the
      induced mutation frequencies at D37 (giving 37% survival) were 31.7 x 10(-4) and
      11.0 x 10(-4) for X-rays and ENU, respectively. For TGr T-cells, the induced
      mutation frequencies at D37 for the same mutagens were 14.4 x 10(-6) and 75.5 x
      10(-6), respectively. Over the dose range studied the relationship appears to be
      linear between the mutation induction of TCR and that of TGr for X-rays or ENU.
      However, X-rays may induce more TCR mutants against less induction TGr T-cells,
      and ENU may cause a reverse result. The sensitivity of the assay of each
      biological endpoint in human blood T-lymphocytes may be different.

PMID- 8876695
TI  - The mutational specificity of furazolidone in the lacI gene of Escherichia coli.
AB  - The mutational specificity of the 5-nitrofuran derivative furazolidone was
      determined in the lacI gene of Escherichia coli. E. coli strain TC3960 (delta
      uvrB, pKM101) was treated with 10 microM furazolidone, yielding an induced
      mutation frequency of 30 times over the spontaneous frequency. Mutations from 88
      furazolidone-induced mutants were analyzed by DNA sequencing: 74 were base
      substitutions, 7 were frameshift mutations, 3 were tandem base substitutions, 3
      were complex mutations and 1 deletion was detected. The specificity of mutation
      was compared to that of furylfuramide (AF2). Differences were observed in both
      the site specificity and the mutagenic specificity of the two 5-nitrofuran
      derivatives. (1) Furazolidone-induced point mutations were observed at both G:C
      and A:T base pairs; 93% of AF2-induced point mutations were targeted to G:C
      sites. (2) At G:C sites approximately equal numbers of G:C-->T:A transversions
      and G:C-->A:T transversions and G:C-->A:T transitions were induced by
      furazolidone; AF2-induced G:C-->T:A transversions outnumbered G:C-->A:T
      transitions 76:49. (3) There was no observable preference for particular
      sequences of furazolidone-induced mutations; the prominent hotspots for AF2
      induced G:C-->T:A transversions, G:C-->A:T transitions and -(G:C) frameshifts
      were at 5'-TGC-3' sequences in the lacI gene. (4) Furazolidone-induced
      frameshifts occurred at homopolymeric sequences suggesting that the mutations
      arose through a strand slippage mechanism; AF2-induced frameshifts occurred at a
      nonreiterated G:C base pair and could be templated, through formation of a
      palindrome, by a sequence 110 base pairs upstream from the site of mutation. The
      significant differences that we observe between the two spectra do not support
      the notion that structurally different 5-nitrofuran derivatives might react in a
      similar manner with DNA to produce premutational lesions with similar
      characteristics.

PMID- 8876696
TI  - Mutational spectra vary with exposure conditions: benzo[a]pyrene in human cells.
AB  - The AHH-1 human lymphoblastoid line was exposed to benzo[a]pyrene under markedly
      different conditions: a single toxic exposure of 30 microM for 28 h, a nontoxic
      exposure of 0.5 microM for 6 days and an exposure approximating estimates of BP
      concentration in the human lung of 20 nM for 20 days. Duplicate cultures
      containing 2 x 10(9) cells each were used to assure the statistical quality of
      the mutational spectra. Point mutational hotspots were observed in bp 215 to 318
      of the third exon of the hprt gene after mutants were selected en masse with 6
      thioguanine, using a combination of denaturing gradient gel electrophoresis and
      high fidelity polymerase chain reaction. The spectra were highly reproducible in
      replicate experiments but varied dramatically among treatment conditions. These
      data demonstrate that mutational spectra were critically dependent upon
      conditions of exposure. The results significantly extend prior reports on this
      subject and clarify an important issue for the use of mutational spectra obtained
      in vitro to create hypotheses about what spectra may be expected in humans in
      vivo. We conclude that commonly used protocols of short-term exposure to
      mutagenic chemicals at high concentrations should not be used to define such
      expectations. Rather, the more difficult protocols of long-term and low
      concentration mutation studies are justified as conditions necessary, although
      perhaps not sufficient, to approximate human in vivo mutational pathways.

PMID- 8876697
TI  - Dose-dependent induction of recessive mutations with N-ethyl-N-nitrosourea in
      primordial germ cells of male mice.
AB  - Using a specific locus test, we previously found that N-ethyl-N-nitrosourea (ENU)
      induces recessive mutations at a relatively high rate in male mouse primordial
      germ cells (PGC) at 8.5, 10.5 and 13.5 days of development (G8.5, G10.5 and
      G13.5). A large difference was observed on the induced mutation rate between 30
      and 50 mg/kg ENU in 10.5-day PGC. We therefore carried out specific locus tests
      to ascertain whether ENU induces recessive mutations in a dose-dependent manner
      in G8.5 and G10.5 PGC. We also gave multiple doses of 25 mg/kg ENU using an 18-h
      interval, the approximate doubling time of PGC at these developmental stages, to
      test for an additive effect on the induced mutations rate. A dose-dependent
      induction of recessive mutations by ENU was observed in both G8.5 and G10.5 PGC,
      and multiple dosing of 25 mg/kg ENU showed an additive effect. Comparing these
      results to data on spermatogonial stem cells, we conclude the capacity to repair
      ENU-induced premutagenic damages is less effective in male mouse PGC at these
      developmental stages than in spermatogonial stem cells.

PMID- 8876698
TI  - Susceptibility of hepatocytes to cell death induced by single administration of
      cycloheximide in young and old F344 rats. Effect of dietary restriction.
AB  - We evaluated the effect of a single dose of 1.0 mg/100 g body weight of
      cycloheximide (CHX) on the susceptibility of hepatocytes to cell death in young
      (6 months old) and old (24 months old) F344 rats fed ad libitum (AL) or on
      dietary restriction (DR), using terminal dUTP nick end labeling (TUNEL). The
      proportion of TUNEL-positive hepatocytes (TPH) at baseline (without
      administration of CHX) was significantly higher in advanced age. However, dietary
      intake did not influence the proportion of TPH at baseline irrespective of age
      Hepatocytes cell death, detected by TUNEL, was induced in the animal by a single
      intravenous injection of CHX. The proportion of TPH increased with time and
      reached a plateau 2.5 h after the administration of CHX in young AL and DR rats
      and old DR rats, but continued to significantly increase 4 hours after the
      administration of CHX in old AL rats. Our results indicate that the death of
      hepatocytes at baseline and susceptibility to cell death was enhanced by CHX in
      hepatocytes of senile rats. Our results also suggest that dietary restriction
      does not suppress the enhancement of cell death at baseline, but prevents age
      associated increase in the susceptibility to cell death.

PMID- 8876699
TI  - The rate of adaptive mutagenesis in Escherichia coli is enhanced by oxygen
      (superoxide).
AB  - Adaptive mutagenesis is that which occurs in non-dividing cells and which allows
      growth under the selective conditions imposed. We now report that reversion of
      amino acid auxotrophies in E. coli fits that definition and is enhanced under
      conditions conducive to oxidative damage to DNA. Thus adaptive mutagenesis was
      approximately 4-fold more frequent in a sodA sodB strain than in the superoxide
      dismutase-replete parental strain and this mutagenesis was suppressed under
      anaerobic conditions. Moreover, a cell permeant manganic porphyrin, capable of
      catalyzing the dismutation of O2-, diminished the rate of occurrence of these
      mutations. Repair of oxidative damage to DNA, in the non-dividing cells, appears
      to provide the opportunity for adaptive mutagenesis.

PMID- 8876700
TI  - Neoplastic transformation of mouse C3H10T1/2 cells following exposure to neutrons
      does not involve mutation of ras gene as analyzed by SSCP and cycle sequencing.
AB  - About 25% of human tumors contain a mutated member of the ras gene family.
      Neutron exposure is an occupational risk in several work places and while we know
      that cells exposed to neutrons can become transformed, the molecular basis of
      this process is not understood. To determine whether neutron-induced cellular
      transformation involves ras mutation, C3H10T1/2 cells were exposed to a single
      dose of 5.9 MeV neutrons. Type II and type III foci were isolated and established
      as cell lines. A total of 34 foci were selected and expanded for analysis of
      tumorigenicity, chromosomal aberrations and mutations in members of the ras gene
      family. The presence of mutations in genomic DNA in N-ras or K-ras of each focus
      was examined by either single-strand conformational polymorphism (SSCP) analysis
      or by asymmetric PCR coupled cell cycle sequence analysis. Although chromosomal
      aberrations were detected at metaphase, no alterations in either ras gene were
      detected. We conclude that in vitro neutron-induced transformation must occur
      through a mechanism other than ras mutation.

PMID- 8876701
TI  - Identification of a DinB/UmuC homolog in the archeon Sulfolobus solfataricus.
AB  - To date, eight closely related homologs of the Escherichia coli UmuC protein have
      been identified. All of these homologs appear to play critical roles in damage
      inducible mutagenesis in enterobacteriaceae. Recently, a distantly related UmuC
      homolog, DinB, has also been identified in E. coli. Using the polymerase chain
      reaction together with degenerate primers designed against conserved regions
      found in UmuC-like proteins, we have identified a new member of the UmuC
      superfamily in the archeon Sulfolobus solfataricus. This new homolog shows high
      sequence similarity to DinB and a lower level of similarity to UmuC. As a
      consequence, we have called this new gene dbh (dinB homolog). Analysis of
      approximately 2.7 kb DNA encompassing the dbh region revealed several open
      reading frames (orfs). One, encoding a putative ribokinase, was located
      immediately upstream of dbh. This orf overlaps the dbh gene by 4 bp suggesting
      that both proteins might be coordinately expressed. Further upstream of the
      ribokinase-dbh locus was another orf encoding a potential ATPase homologous to
      two uncharacterized S. cerevisiae proteins (YD9346.02c and SC38KCXVI_20) and
      another E. coli DNA repair protein, RuvB. While this is the first report of a
      UmuC-like homolog in an archeon, we detected additional homologs using protein
      sequence comparisons in Gram-positive bacteria, cyanobacteria, and among
      potential human EST products, indicating that UmuC-related proteins comprise a
      ubiquitous superfamily of proteins probably involved in DNA repair and
      mutagenesis.

PMID- 8876702
TI  - A place for statistics in the generation and analysis of genetic toxicity data: a
      response to 'rodent mutation assay data presentation and statistical assessment'.

PMID- 8876703
TI  - Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia:
      results of a double-blind, placebo-controlled, randomized clinical trial using
      two doses of the aromatase-inhibitor atamestane. Atamestane Study Group.
AB  - BACKGROUND: The concept of estrogen withdrawal by an aromatase inhibitor in the
      treatment of benign prostatic hyperplasia (BPH) was assessed in a prospective,
      randomized, double-blind, placebo-controlled multicenter trial. METHODS: Two
      hundred and ninety-two patients with clinical symptoms of BPH were randomly
      allocated to one of the following treatments for 48 weeks: placebo or the
      selective aromatase inhibitor, atamestane, at a daily dose of 100 mg or 300 mg.
      Both doses of atamestane significantly reduced serum concentrations of estradiol
      and estrone, and produced a slight, dose-dependent, counter-regulatory increase
      in peripheral androgen concentration. RESULTS: Clinical symptoms improved during
      treatment in all three groups. Even after 48 weeks, the effect of active
      treatment did not exceed the effect seen with placebo. Overall tolerance of 100
      mg atamestane was excellent, but 300 mg showed a slightly increased incidence of
      side effects compared with placebo. CONCLUSIONS: The conclusion from this study
      is that the reduction in estrogen concentration using the selective aromatase
      inhibitor atamestane has no effect on clinically established BPH.

PMID- 8876704
TI  - Expression of transforming growth factor-beta 1 in rat ventral prostate and
      Dunning R3327 PAP prostate tumor after castration and estrogen treatment.
AB  - BACKGROUND: In normal prostate, TGF-beta 1 is associated to castration induced
      apoptosis. Combined castration and estrogen treatment, but not castration alone,
      induces apoptosis in the Dunning R3327 PAP adenocarcinoma. METHODS: TGF-beta 1
      expression in rat ventral prostate (VP) and Dunning R3327 PAP tumor was studied
      after castration and estrogen treatment, using competitive RT-PCR, in situ
      hybridization and immunohistochemistry. RESULTS: TGF-beta 1 mRNA level was 6
      times higher in the tumor than in the VP. Combined castration and estrogen
      treatment increased TGF-beta 1 mRNA levels in the tumor from day 3, while
      castration did not. The TGF-beta 1 expression was located in the epithelial
      cells. CONCLUSIONS: The Dunning R3327 PAP tumor contains high levels of TGF-beta
      1, which are further increased by combined castration and estrogen treatment.
      However, since this increase is not apparent until day 3, TGF-beta 1 probably
      does not contribute to the known induction of apoptosis in the tumor at day 1
      after combined castration and estrogen treatment.

PMID- 8876705
TI  - Effects of the lipidosterolic extract of Serenoa repens (Permixon) on human
      prostatic cell lines.
AB  - BACKGROUND: Permixon is a drug used in the treatment of benign prostatic
      hyperplasia. We studied its androgenic and antiandrogenic effects in the
      prostatic cell lines LNCaP and PC3, respectively responsive and unresponsive to
      androgen stimulation. METHODS: We performed FACScan analysis to investigate
      toxicity, 3H thymidine and 35S methionine incorporation to determine
      antiproliferative and metabolic effects, electron microscopy to study
      ultrastructural changes and cotransfection experiments to elucidate the role of
      wild type androgen receptor. RESULTS: In LNCaP cell line, Permixon induced a
      double proliferative/differentiative effect, not observed in PC3 cells. In PC3
      cells cotransfected with wild-type androgen receptors and CAT reporter genes
      under the control of a androgen responsive element, the drug inhibited androgen
      induced CAT transcription. CONCLUSIONS: Our data indicate a role of the androgen
      receptor in mediating the effects of Permixon in LNCaP cells. Cotransfection
      experiments in PC3 cells support a clear antiandrogenic action of the drug.

PMID- 8876706
TI  - Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign
      prostate hyperplasia: a randomized international study of 1,098 patients.
AB  - BACKGROUND: Controversy regarding the relative efficacy of treatments for the
      relief of the symptoms of benign prostatic hyperplasia (BPH). METHODS: This was a
      6-month double-blind randomized equivalence study that compared the effects of a
      plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg
      finasteride) in 1,098 men with moderate BPH using the International Prostate
      Symptom Score (IPSS) as the primary end-point. RESULTS: Both Permixon and
      finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of
      life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P =
      0.035), with no statistical difference in the percent of responders with a 3
      ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and
      serum PSA levels (-41%); Permixon improved symptoms with little effect on volume
      (-6%) and no change in PSA levels. Permixon fared better than finasteride in a
      sexual function questionnaire and gave rise to less complaints of decreased
      libido and impotence. CONCLUSIONS: Both treatments relieve the symptoms of BPH in
      about two-thirds of patients but, unlike finasteride, Permixon has little effect
      on so-called androgen-dependent parameters. This suggests that other pathways
      might also be involved in the symptomatology of BPH.

PMID- 8876707
TI  - Development of anemia and recovery in prostate cancer patients treated with
      combined androgen blockade and radiotherapy.
AB  - BACKGROUND: The objective of this study was to document previously unreported
      anemia in prostate cancer patients treated with neoadjuvant combined androgen
      blockade (CAB) and pelvic radiotherapy (XRT). METHODS: Four institutions treated
      141 patients (mean age +/- SD, 70.9 +/- 6.5 years) with zoladex 3.6 mg injection
      subcutaneous depot monthly and flutamide 250 mg orally three times per day for 2
      months (CAB), followed by zoladex and flutamide with concurrent XRT (65-70 Gy)
      for 7-8 weeks. RESULTS: After the XRT, the patients were randomized to receive no
      further treatment (Z- group, 71 patients) or zoladex alone (Z+ group, 70
      patients) for 2 years. Hemoglobin (Hb) levels decreased > or = 1 g/dl (mean +/-
      SE, 2.1 +/- 0.1 g/dl) in 98/131 patients (75%) after 2 months of CAB, and > or =
      2 g/dl (3.1 +/- 0.1 g/dl; range, 0.1-6.8 g/dl) in 106/131 patients (81%) after an
      additional 2 months of CAB with concurrent XRT. The decrease in Hb levels
      paralleled the decreased in testosterone levels. No evidence of blood loss or
      hemolysis was found. CONCLUSIONS: There was no association between incidence or
      rate of Hb decrease and race, age, or pretreatment prostate-specific antigen
      (PSA) levels. However, the recovery from anemia after completion of CAB in
      African-Americans was slower than in Whites in the Z+ group (P < 0.04). Whereas
      grade 1 hematologic toxicity may occur in < 5% of the patients with zoladex
      alone, and approximately 6% with flutamide alone, in our study 81% showed mild to
      pronounced anemia. Since anemia has not been observed after treatment with XRT
      alone or XRT followed by zoladex, we conclude that the anemia was due to CAB.
      Recognition of this side effect should avoid unnecessary diagnostic evaluations.

PMID- 8876708
TI  - Prostate cancer and smoking: a review of case-control and cohort studies.
AB  - BACKGROUND: The purpose of this study was to undertake a systematic analysis of
      the relation between smoking and prostate cancer. METHODS: All published case
      control and cohort studies including relevant data on this topic were collected.
      The magnitude of potential sources of divergent results among case-control
      studies was estimated comparing current, former, and ever to never smokers,
      stratified by type of controls (hospital vs. population) and by race. Cohort
      studies were discussed individually. RESULTS: Neither a clinically nor a
      statistically significant association between smoking and prostate cancer seems
      likely, but it cannot be ruled out entirely. The association between other
      purported risk factors and prostate cancer is not likely to be confounded by the
      incomplete measurement and control for smoking habits because smoking and
      prostate cancer are not related. CONCLUSIONS: For a valid assessment of other
      risk factors in prostate cancer patients the collection of complete smoking
      information is therefore less critical than in patients with other diseases. For
      a definitive assessment of the effect of smoking on prostate cancer incidence and
      mortality however, future studies need to focus on the collection of information
      on lifetime smoking habits, including tar exposure.

PMID- 8876709
TI  - Differential expression of 5 alpha-reductase isoenzymes in the human prostate and
      prostatic carcinomas.
AB  - BACKGROUND: Steroid 5 alpha-reductase is essential for the intracellular
      accumulation of dihydrotestosterone (DHT), which mediates androgen effects on
      target tissue. METHODS: In the present study, we describe the differential
      expression and cellular localization of 5 alpha-reductase 1 and 2 isoenzymes in
      the human prostate, and untreated and hormone-resistant prostatic carcinomas. The
      secretory epithelium of normal and hyperplastic glands showed strong nuclear 5
      alpha-reductase 1 reactivity. Accordingly, the DHT forming 5 alpha-reductase
      process in secretory luminal cell types may be mediated predominantly by the type
      1 isoenzyme. The androgen-independent basal cell layer variably expressed type 1
      and 2 isoenzymes in nuclear and cytoplasmatic compartments. This suggests that
      circulating androgens are involved to control the basal cell layer, which
      represents the proliferative compartment of the human prostate. RESULTS: When
      compared with benign prostate tissue, increased 5 alpha-reductase reactivity was
      detected in prostate cancer, particularly in high-grade tumors and androgen
      insensitive states of the disease. In cancerous lesions, the type 1 isoenzyme
      tended to shift to the cytoplasm, while the nuclear staining remained unchanged
      or slightly increased. Referring to the type 2 isoenzyme, increased cytoplasmatic
      and nuclear enzyme activity was detected in malignant cells when compared with
      adjacent benign prostate tissue. Even endocrine differentiated tumor cells that
      consistently lacked the nuclear androgen receptor variably expressed 5 alpha
      reductase immunoreactivity. CONCLUSIONS: Although the functional significance of
      the differential subcellular localization of type 1 and 2 isoenzymes is currently
      unknown, the present data suggest that prostate cancer retains the DHT forming 5
      alpha-reductase process in high-grade lesions and recurrent disease. Accordingly,
      circulating androgens may be still significant in these hormone-refractory
      malignancies.

PMID- 8876710
TI  - Radical resection of intramedullary spinal cord tumors without cavitron
      ultrasonic aspirator or CO2 laser: a "two stage" technique.
AB  - A simple and efficient procedure called the "two stage" technique for total
      removal of intramedullary tumors is described. MRI, CUSA, and CO2 laser have
      revolutionized the diagnosis and treatment of spinal cord tumors, allowing
      precise demonstration of the lesions and safe removal without exacerbating
      neurosurgical deficit. These useful and efficient apparatus are not only
      expensive, they are still not yet available in many neurosurgical centers
      throughout the world. Neurosurgeons deprived of these important tools can,
      however, approach or even equate the current clinical results. The "two stage"
      technique is not meant to substitute for CUSA, CO2 laser, and MRI.

PMID- 8876711
TI  - Neurosurgery in Zimbabwe.

PMID- 8876712
TI  - Aggressive surgery for intramedullary tumor of cervical spinal cord.
AB  - BACKGROUND: Intramedullary tumors of the cervical spinal cord are common and many
      believe they are amenable to an aggressive approach. However, surgical removal of
      intramedullary tumors of the cervical spinal cord is still controversial because
      of the great risk of respiratory dysfunction or quadriplegia or both upon
      resection of the tumor. METHODS: We present a consecutive series of 58 patients
      who underwent surgical treatment for intramedullary tumors of the cervical spinal
      cord. Surgical results are analyzed to refine our indications for surgery and its
      timing. The roles of preoperative radiotherapy and posttherapeutic cord
      appearance and function are discussed. RESULTS: Tumors were totally resected in
      50 (86.2%), subtotally in seven and partially in one patient. Forty-five (77.6%)
      patients had improved neurologic status postoperatively. Intramedullary tumors in
      the cervical area have better results from surgery than intramedullary tumors in
      other levels of the spine. Patients with moderate neurologic deficits can recover
      remarkably well after total tumor removal. Laser surgery is especially helpful
      for lipoma. Preoperative radiotherapy should be avoided because it is associated
      with difficult surgery and poor clinical outcome. The thin spinal cord can
      function surprisingly well. CONCLUSIONS: We conclude that intramedullary tumors
      of the cervical spinal cord are amenable to total surgical removal. Surgery is
      suitable when a patient presents with a moderate neurologic deficit. Proficient
      surgical technique for total tumor resection is necessary for good results.
      Preoperative radiotherapy contributes to difficult surgery and poor prognosis,
      and is not recommended.

PMID- 8876713
TI  - Intramedullary spinal cord metastasis: report of three cases and review of the
      literature.
AB  - BACKGROUND: Intramedullary spinal cord metastasis is rare; but it is being
      encountered with increasing frequency. Optimal treatment after diagnosis remains
      controversial. METHODS: In the last 3 years, we have encountered three cases of
      intramedullary metastasis presenting as focal mass lesions with minimal systemic
      evidence of cancer. We present our results in these patients and review the
      literature in an effort to more optimally define both the natural course of this
      disease, as well as a potential subset of patients who might benefit from more
      aggressive treatment. RESULTS: With the availability of more sensitive imaging
      techniques, these tumors are being diagnosed with increasing frequency. Magnetic
      resonance imaging is sensitive, but nonspecific, in distinguishing intramedullary
      spinal cord metastases from primary cord tumors. Urgent biopsy is often necessary
      prior to definitive treatment. Radiation with chemotherapy significantly prolongs
      survival. Radical subtotal resection may offer additional quality survival,
      especially in cases of metastatic melanoma with an occult primary. CONCLUSIONS:
      Regardless of treatment, many patients survive less than 1 year. Intramedullary
      spinal cord metastasis is a devastating condition, but with appropriate diagnosis
      and aggressive treatment, selected patients may have substantially increased
      survival.

PMID- 8876714
TI  - Primary spinal epidural non-Hodgkin's lymphomas: a clinical study.
AB  - BACKGROUND: The spinal epidural space is an uncommon presenting site in primary
      non-Hodgkin's lymphoma. The occurrence of spinal epidural disease ranges from
      0.1%-6.5% among patients with non-Hodgkin's lymphoma. METHODS: We report a
      retrospective study regarding 19 patients with primary epidural non-Hodgkin's
      lymphomas analyzing the factors influencing prognosis of this tumor with emphasis
      on treatment. RESULT: Ten patients were females and nine males. The neurologic
      conditions of patients were assessed preoperatively and postoperatively according
      to Shaw's classification for neurologic disability. All cases underwent surgery
      accompanied by radiotherapy in 16 cases as well as chemotherapy in 13 cases.
      Histologically, the tumor proved to be a low-grade non-Hodgkin's lymphoma in
      three cases, intermediate-grade in four cases and, high-grade in 12 cases. At
      average follow-up of 7.2 years (range 5-15 years), 15 patients had died after an
      average interval of 31 months from treatment (range 3-130 months) and four
      patients are alive after an average interval of 61 months (range 32-86 months).
      CONCLUSION: It appears that the outcome in these patients depends on the gravity
      of preoperative deficits, whereas the survival is influenced by the type of
      treatment.

PMID- 8876715
TI  - Acute spontaneous spinal epidural hematoma: the influence of magnetic resonance
      imaging on diagnosis and treatment.
AB  - BACKGROUND: Acute spontaneous spinal epidural hematoma (ASSEDH) is rare and its
      treatment standard were set prior to the era of magnetic resonance imaging (MRI).
      Recent data provided by this new technique necessitate a critical review of these
      standards. METHODS: A case of ASSEDH diagnosed by MRI and confirmed at surgery is
      presented. In addition, all cases of ASSEDH reported in the pertinent literature
      since 1987 were reviewed and compared with those cases described earlier.
      RESULTS: Since the introduction of MRI, the mean incidence of ASSEDH cases
      reported in the literature has increased from 2.2 to 6.4 new cases per year, with
      a remarkable rise in the percentage of those cases that did not require surgical
      treatment from 1.5% before the era of MRI to 29% thereafter. CONCLUSION: ASSEDH
      runs a benign course more often than previously estimated and, therefore, the
      choice of the treatment should be decided for each case individually. Urgent
      surgical decompression remains the treatment method of choice for patients with
      ASSEDH presenting with disabling neurologic deficit.

PMID- 8876716
TI  - The effects of taxol, methylprednisolone, and 4-aminopyridine in compressive
      spinal cord injury: a qualitative experimental study.
AB  - BACKGROUND: Taxol is a diterpene alkaloid that stimulates tubulin production in
      cells. It may be effective in preserving the cytoskeleton of spinal cord axons
      after injury. METHODS: Thirty-nine rats were submitted to spinal cord
      compression. The animals were divided into three groups that received taxol
      (18.75 mg/m2), methylprednisolone (30 mg/kg), or 4-aminopyridine (1 mg/kg). Taxol
      was administered as one dose immediately after injury and two additional doses on
      days 14 and 21. Methylprednisolone was given as a single injection immediately
      postinjury. Four-aminopyridine was administered on days 25, 26, and 27. A group
      of nine injured animals served as a control without any treatment. Evoked
      potentials were recorded before, during, and 4 weeks postinjury. Behavioral tests
      were measured to evaluate recovery of motor function. RESULTS: The taxol and
      methylprednisolone-treated animals demonstrated a significant improvement in
      comparison with the control group. No functional improvement was found at 1 mg/kg
      treatment of 4-aminopyridine in rats. CONCLUSIONS: We conclude that taxol and
      methylprednisolone given shortly after the compression injury improve functional
      outcome after an incomplete spinal cord injury.

PMID- 8876717
TI  - Microvascular decompression for trigeminal neuralgia in patients with multiple
      sclerosis.
AB  - BACKGROUND: Microvascular decompression (MVD) of the trigeminal nerve is a well
      established procedure for the treatment of idiopathic trigeminal neuralgia.
      Multiple sclerosis (MS) has long been considered a contraindication for this
      procedure, due to the known polycentric nature of the disease. Medical treatment
      followed by percutaneous procedures provide relief for the great majority of
      these patients. There exists a small subgroup of patients with trigeminal
      neuralgia who are diagnosed with MS only after a microvascular decompression
      procedure has been performed. Furthermore, management of the patient with known
      MS whose pain continues to recur, despite maximal medical therapy and multiple
      percutaneous procedures, can be exceedingly difficult. METHODS: Five patients
      with MS, three who had undergone multiple unsuccessful percutaneous procedures
      and two in whom the diagnosis of MS had not been established, underwent
      exploration of the cerebellopontine angle. Three patients underwent MVD alone,
      and two (both with known MS) underwent MVD and partial section of the trigeminal
      nerve. RESULTS: Patients who underwent microvascular decompression alone did not
      have satisfactory relief of pain. Patients who underwent partial sectioning of
      the nerve did better. CONCLUSIONS: Patients with MS and symptoms of typical
      trigeminal neuralgia may benefit from exploration of the cerebellopontine angle
      and partial sectioning of the nerve. MVD alone fails to provide adequate or
      reliable relief of pain.

PMID- 8876718
TI  - Spinal cord stimulation for chronic pain in peripheral neuropathy.
AB  - BACKGROUND: Spinal cord stimulation (SCS) has been used for the relief of
      chronic, intractable pain for over 2 decades. Recent technologic improvements in
      hardware have resulted in improved clinical outcome. We report our experience
      with epidural spinal cord stimulation for pain control of peripheral neuropathy
      for the past 15 years. METHODS: An analysis of our series of 276 patients
      revealed 30 patients diagnosed with peripheral neuropathy. The mean age of the 16
      men and 14 women in the study was 62.4 years. The anatomic sources of pain
      included thorax, as well as upper and lower limbs. Causes of intractable pain
      included postherpetic neuralgia, intercostal neuralgia, causalgic pain, diabetic
      neuropathy, and idiopathic neuropathy. RESULTS: Nineteen patients reported relief
      of pain on trial stimulation and had their systems permanently implanted. At an
      average of 87 months' follow-up, 14 of these patients achieved long-term success
      in control of chronic pain (47% of all patients included in this study). Six
      patients reported excellent pain relief (> 75% pain relief), eight described good
      results (> 50% pain relief), and six had poor pain relief (< 50% pain relief).
      CONCLUSION: SCS is an effective therapy for pain syndromes associated with
      peripheral neuropathy. Causalgic and diabetic neuropathic pain seem to respond
      relatively well. whereas postherpetic pain and intercostal neuralgia syndromes
      seem to respond less favorably to the long-term beneficial effects of SCS. This
      information will be useful in the selection of patients with peripheral
      neuropathic pain who could be helped by SCS.

PMID- 8876719
TI  - A comparison of children with suprasellar germ cell tumors and
      craniopharyngiomas: final height, weight, endocrine, and visual sequelae after
      treatment.
AB  - BACKGROUND: Although treatment results of craniopharyngiomas and germ cell tumors
      in children have been reported extensively, the relationship between various
      posttreatment sequelae and the nature of the tumor is not well understood.
      METHODS: From 1968-94, 47 children with 23 suprasellar germ cell tumors and 24
      craniopharyngiomas were treated at Gunma University Hospital, Japan. Forty
      survivors were assessed with regard to Karnofsky scores, visual scores, final
      height, final weight, and other endocrine sequelae as long-term functional
      prognostic indicators. RESULTS: Kaplan-Meier life-table estimates and Karnofsky
      scores were not significantly different between the two histologic groups. The
      visual function of survivors did not differ significantly at diagnosis. However,
      the final visual function following treatment in the germ cell tumor group was
      better than in the craniopharyngioma group (p < 0.05). Antidiuretic hormone
      secretion was significantly impaired at diagnosis in the germ cell tumor group (p
      < 0.0001). However, there was only a marginally significant difference in
      posttreatment persistent diabetes insipidus. Craniopharyngioma children were
      shorter and more obese at diagnosis (p < 0.02), and became much more obese than
      germinoma children with the same hormone therapy (p < 0.003), although the height
      difference became insignificant following growth hormone treatment. CONCLUSIONS:
      Children with craniopharyngiomas tended to have more visual disturbances,
      increased dwarfism and obesity, and less diabetes insipidus than patients with
      germ cell tumors despite adequate therapy. The method of quantifying visual
      function may in itself be useful.

PMID- 8876720
TI  - Subdural-peritoneal shunt: treatment for bilateral chronic subdural hematoma.
AB  - BACKGROUND: Various modalities have been advocated and practiced to maximize the
      effectiveness of treatment for chronic subdural hematoma. Most patients with
      chronic subdural hematoma are successfully treated with simple burr-hole
      evacuation and external drainage. Hematomas with thick membranes have been found
      to persist or recur, sometimes necessitating reoperation or major surgery;
      however, they have been satisfactorily treated by repeated drainage or tapping as
      well. Chronic subdural hematoma can sometimes become an intractable and difficult
      problem. In recurring chronic collections, subdural-peritoneal shunts have been
      used as a mode of treatment. Treatment of recurrent subdural collection in
      infants has been successfully achieved by using subdural-peritoneal shunts. There
      is also literature to support a similar treatment for recurrent chronic subdural
      hematoma in older patients. CASE DESCRIPTION: We report a case of recurrent
      bilateral chronic subdural hematoma in an adult, which was successfully managed
      by repeated burr-hole evacuation initially, followed by insertion of a subdural
      peritoneal shunt. The patient did well clinically, and computerized axial
      tomography did not reveal any subdural collection on follow-up. CONCLUSION:
      Treatment of recurrent chronic subdural hematoma is usually straightforward;
      however, it can sometimes be refractory to regular treatment. In managing such
      cases, we recommend placement of a subdural-peritoneal shunt in preference to a
      more complicated craniotomy and membranectomy.

PMID- 8876721
TI  - Cyclosporine-A increases locomotor activity in rats with 6-hydroxydopamine
      induced hemiparkinsonism: relevance to neural transplantation.
AB  - BACKGROUND: The immunosuppressant cyclosporine-A (CsA) is the primary drug for
      neural transplantation in Parkinson's disease. However, little is known of its
      direct effects on movement disorders. Our previous observation of increased
      locomotor activity in normal rats injected with CsA prompted us to investigate
      further the effects of CsA on hemiparkinsonian rats. METHODS: We examined the
      effects of CsA with 6-hydroxydopamine-induced hemiparkinsonism. The animals were
      randomly assigned to either intraperitoneal injections of CsA (15 mg/kg) or olive
      oil (the vehicle used for CsA) for 32 days. All animals were tested using the
      elevated body swing test, and the spontaneous and the amphetamine-induced
      rotational tests prior to and following the 32-day drug regimen. RESULTS: As
      revealed by the elevated body swing test, CsA-treated rats had significantly
      higher mean percent contralateral (to the lesion) swings compared to their
      pretreatment level (p < 0.01) or to vehicle-treated rats at posttreatment (p <
      0.005). In the spontaneous rotational test, CsA-treated rats displayed
      ipsilateral (to the lesion) rotations which were significantly higher than their
      pretreatment rotational behavior (p < 0.005) or the posttreatment rotational
      behavior of olive oil-treated rats (p < 0.0001). Similarly, CsA-treated rats
      displayed significantly more amphetamine-induced ipsilateral rotations compared
      to their or the olive oil-treated rats pretreatment level (p < 0.05). CONCLUSION:
      Our present observations extend our previous findings on motor alterations
      produced by CsA on normal rats to hemiparkinsonian rats. These results taken
      together would suggest that CsA may interact with the locomotor effects observed
      following neural transplantation with adjunctive CsA immunosuppression.

PMID- 8876722
TI  - Histology after dural grafting with small intestinal submucosa.
AB  - BACKGROUND: The search for the ideal dural substitute continues, inasmuch as
      available materials have significant limitations. Xenogeneic porcine small
      intestinal submucosa (SIS) has been successfully used as a soft tissue graft in
      several body organ systems, and it was logical to evaluate its use as a dural
      replacement. METHODS: Twenty rats underwent bihemispheric craniectomy with dural
      resection. SIS onlay grafting on one side was performed. Histologic assessment
      was obtained at 7 and 28 days after dural grafting and included descriptive
      evaluation and quantitative scoring of graft-site thickness, vascularity, and
      cellular density. The total scores for the respective groups were compared using
      the Student's t test, significance being accepted for a p value < 0.05. RESULTS:
      Histologic evaluation showed graft infiltration by spindle-shaped mononuclear
      cells, deposition of connective tissue, and neovascularity. This pattern is
      consistent with the previously described incorporation and remodeling of the SIS
      graft at other sites. A significant difference between the histologic scores of
      the SIS graft site and control site was found at 7 days (3.4 +/- 0.8 versus 0.1
      +/- 0.1) and at 28 days (4.6 +/- 1.1 versus 2.2 +/- 0.5). No evidence of adverse
      effect on the underlying cortex was observed. CONCLUSIONS: The results of this
      preliminary study utilizing porcine SIS as a dural substitute are promising and
      therefore justify further chronic studies.

PMID- 8876723
TI  - Ossification of the ligamentum flavum with myelopathy.

PMID- 8876724
TI  - A place for neurosurgery in a developing country?

PMID- 8876725
TI  - EBV-B cell interactions: immortalization, rescue from apoptosis, tumorigenicity
      (a short review).
AB  - Translocation of the c-myc gene to an immunoglobulin locus is a rate-limiting
      step in the genesis of three B-cell derived tumors: Burkitt lymphoma (BL) in
      humans, mouse plasmacytoma (MPC) and rat immunocytoma. Its consequences have been
      best analyzed in BL. They involve a non-immunological and an immunological
      component. The former acts by preventing the B cell from leaving the cycling
      compartment and entering the resting stage when programmed to do so. The latter
      acts by the down regulation of certain HLA class I polymorphic specificities,
      adhesion molecules and EBV encoded proteins. According to our interpretation, the
      translocation fixes the BL cell in a phenotypic window that can be referred to as
      "a resting cell that is not resting". The linking of c-myc to immunoglobulin
      sequences in a B cell leads to constitutive myc expression. In spite of its
      switch to a "resting phenotype", the cell is therefore unable to leave the
      cycling compartment. Normally, EBV-carrying B-blasts face immune controls. They
      can only proliferate in immunodefectives, as in XLP or transplant lymphoma. Due
      to its "resting" rather than B-blast phenotype and the correlated defective
      expression of certain EBV, HLA and adhesion molecules, the BL cell is not
      rejected by the EBV-specific immune response, however. The down-regulation of
      EBNA 2-6 in the BL cell may be also considered in relation to viral latency. The
      exclusive expression of EBNA 1 in the BL cell reflects the adaptation of the
      virus to prolonged persistence in long lived resting B cells, an important if not
      exclusive reservoir of the latent virus. Normal B cells that fail to be activated
      by appropriate mitogens or antigens within a limited period of time undergo
      apoptosis, as a rule. EBV may protect resting B cells. The role of the only
      virally encoded protein they are known to express, EBNA 1, remains to be explored
      in this respect. EBV infected immunoblasts are protected from apoptosis by the
      LMP 1 induced elevation of bcl-2 expression. During the lytic cycle when cellular
      protein synthesis is switched off by the early viral proteins, a member of the
      early protein group, a bcl-2 homologous protein encoded by the BHRF1 gene, takes
      over the function to protect against untimely apoptosis.

PMID- 8876726
TI  - Antibiotics and the host-parasite relationship (a short review).
AB  - The last twenty years have witnessed an increasing interest in the concomitant
      action that an antibiotic may have on cells other than its primary target, the
      bacterial or fungal cell. It is now recognized that some may exert direct
      immunomodulatory effects (positive and negative) on cells of the host's immune
      response (polymorphonuclear neutrophils, macrophages and T lymphocytes). Others
      may concentrate within phagocytic cells, remain bioactive therein and be
      transported involuntarily to sites of infection. In addition, there is evidence
      that a number of antibiotics, primarily those which act by inhibition of
      bacterial protein synthesis, interfere with the expression of structural
      virulence factors rendering the producer bacteria more or less susceptible to
      phagocytic ingestion and killing. It remains likely that some of all of these
      activities may occur in vivo during therapy.

PMID- 8876728
TI  - Alternaria mycotoxins in black rot lesion of tomato fruit: conditions and
      regulation of their production.
AB  - Alternaria represents the most colon decay organism of the post-harvest tomato
      fruit. The prevalent type of decay, black rot lesion, is caused by Alternaria
      alternata which may invade tomato tissue damaged by sun scald. The mainly natural
      mycotoxins produced in rotted tomato are alternariol (AOH), alternariol
      monomethyl ether (AME), and tenuazonic acid (TA). Whereas, altertoxin-I and -II
      (AT-I and -II), in addition to AOH, AME and TA were produced by local A.
      alternata in a synthetic medium. The optimum temperature for toxin production by
      A. alternata IMI 89344 was 28 degrees C for AOH and AME, 21 degrees C for TA and
      14 degrees C for AT-I and -II. The growth and toxin were produced in a noticeable
      amount at 7 degrees C but drop at 35 degrees C. Significant inhibition in these
      toxins was attained at 500 ppm cinnamon oil in YES-Czapek's medium and in
      homogenate of tomato.

PMID- 8876727
TI  - Identification of different circulating autoantibodies in patients with bullous
      pemphigoid and pemphigus vulgaris by means of immunoblotting.
AB  - Immunoblotting studies with salt-split human epidermis were performed on sera
      from 15 patients with pemphigus vulgaris and 20 patients with bullous pemphigoid
      by using peroxidase-labelled antihuman IgG and IgA. Eleven sera of pemphigus
      vulgaris antigen. Most of the sera gave additional specific bands at 210 and 80
      kD, with lower intensity. The sera of 4 patients, 3 of them were in clinical
      remission, did not yield specific bands. Seventeen sera of the 20 bullous
      pemphigoid patients yielded a 220-230 kD protein band against the major bullous
      pemphigoid antigen and 4 of them gave another specific band at 160-180 kD. Five
      sera produced multiple bands (220, 130, 100 and 75 kD). IgA antibodies against
      the major bullous pemphigoid antigen were demonstrated in 2 cases with IgA
      deposits along their basement membrane, as revealed by direct immunofluorescence.
      The immunoblot patterns correlated only weakly with the clinical findings in
      bullous pemphigoid. There was a considerable diversity in both clinical findings
      and immunoblot patterns.

PMID- 8876729
TI  - Activity of nitrogen fixation and nitrogen assimilation enzymes in soybean plants
      inoculated with Bradyrhizobium japonicum strains.
AB  - In studying the symbiotic associations of 8 Bradyrhizobium japonicum strains with
      two soybean varieties (NS-10 and NS-21), we determined the activity of nitrogen
      fixing (nitrogenase, NG) and nitrogen assimilation (glutamine synthetase, GS) and
      glutamate dehydrogenase (GDH) enzymes and the content of soluble proteins. The
      number of nodules was not in correlation with dry matter mass and nitrogen
      content. Dry matter mass and nitrogen content in the nodules of the soybean
      varieties in association with Bradyrhizobium strains 1, 1a, 2b, 2/1, 1003 and 8k
      turned out to be significantly higher than mass and nitrogen content of those in
      association with B. japonicum strains 17z and 2k. The results obtained indicate
      that the activity of the enzymes NG and GS in plants correlates with nitrogen
      fixation for both varieties on average, while the activity of GDH enzyme is
      conditioned by the specificity of variety and the Bradyrhizobium japonicum
      strains.

PMID- 8876730
TI  - Timing of first restorations before, during, and after a preventive xylitol
      trial.
AB  - An independent longitudinal retrospective analysis of the timing, number, and
      cost of tooth restorations was conducted for all subjects (n = 313) in the age
      cohort of a municipal health center, in which two consecutive field trials of up
      to 3 years on the caries-preventive effect of the use of xylitol chewing gum were
      conducted (Ylivieska study, 1982-85). A computer program calculated the post
      eruptive timing of the first restorations on each permanent tooth surface, and
      survival analysis methods were applied before, during, and after the trials. The
      cost of restorations was then calculated. The total number of new restored
      surfaces was 4.0 per child in the xylitol group and 9.3 in the controls during
      the decade after onset of the trial. The number of restorations on the occlusal
      surfaces of the first molars leveled off at 40-50% in the xylitol group and at
      about 60-70% in the control group. Plateaus for the second molars were at 30-40%
      and 60-70%, respectively. The time lag for the first restorations was longer in
      the xylitol group for the proximal and other smooth surfaces. A marked difference
      in favor of the xylitol group was observed in the proximal surfaces of the upper
      incisors (for example, the mesial surface of the upper mesial incisor for girls:
      log-rank chi-square = 11.1, p < 0.001). The preventive effect was most pronounced
      in teeth that had erupted during the trial. This analysis indicated that
      participation of subjects in the xylitol chewing gum trials resulted in a
      significant reduction in the number of first restorations and hence in costs
      during the decade after the onset of gum use.

PMID- 8876731
TI  - Oral mucosal changes and associated factors among male industrial workers with or
      without access to subsidized dental care.
AB  - Oral mucosal changes and associated factors were studied among male industrial
      workers in southern Finland. Two groups, with or without access to an employer
      provided dental benefit scheme, were compared. A multiple-choice questionnaire
      followed by clinical examinations was completed by 325 (81%) subsidized workers
      and 174 (69%) controls. In both groups 52% of the subjects had some oral mucosal
      change, and there were no significant differences between the groups in the
      location distribution of the changes. Smoking was significantly associated with
      redness of the oral mucosa (p < 0.001), coating (p < 0.001), and leukoplakia (p <
      0.01), whereas denture wearing was associated with ulcers (p < 0.05), hyperplasia
      (p < 0.001), and redness (p < 0.001). Among denture wearers non-acceptable
      dentures were significantly associated with hyperplasia (p < 0.001). The
      subsidized group had better dentures, although this did not significantly benefit
      their oral mucosal status.

PMID- 8876732
TI  - Fluoride release and uptake in vitro from a composite resin and two orthodontic
      adhesives.
AB  - The aim of this study was to investigate the fluoride release and uptake
      characteristics of a composite resin (Tetric) and two orthodontic adhesives (VP
      862 and Saga Bond), with a type-II glass ionomer cement (Ketac Fil) as a control.
      Test specimens in 2 ml deionized water released fluoride over a period of 33
      days. Ketac Fil released 54 and 15 times more fluoride than Tetric after 24 h and
      1 month, respectively, whereas the two adhesives released amounts between these
      values. Specimen exposure to 1000-ppm NaF solution increased the 24-h fluoride
      release from all materials, with near pre-exposure levels reached after 2-3 days.
      Ketac Fil had a tendency to recharge not seen with the other materials. The
      ytterbium trifluoride filler in Tetric has a very low water solubility, and it is
      therefore suggested that the increases in fluoride release from Tetric after
      exposure to fluoride were most probably due to release of surface-retained
      fluoride.

PMID- 8876733
TI  - Can frontal sinus development be used for the prediction of skeletal maturity at
      puberty?
AB  - The precision of a new procedure predicting skeletal maturity on the basis of
      frontal sinus development was tested in 59 boys with an Angle class-II division-1
      malocclusion. Lateral head films were used for the analysis of frontal sinus
      development, and handwrist radiographs were used for the assessment of skeletal
      maturity. The results showed that skeletal maturity could be predicted with a
      certainty of about 85% when using a 1-year prediction interval and with a
      certainty of about 75% when using a 2-year prediction interval. In conclusion,
      the study showed that skeletal maturity can be predicted with rather high
      accuracy by means of the analysis of frontal sinus development as imaged on
      lateral headfilms.

PMID- 8876734
TI  - The effect of parental dental health behavior on that of their adolescent
      offspring.
AB  - This study was designed to investigate the effect of parental dental health
      behavior on that of their adolescent offspring. The data stemmed from The
      Norwegian Longitudinal Health Behavior Study performed in 1993 in the County of
      Hordaland in Norway and comprised separate questionnaires for both parents and a
      16-year-old child in 436 family units. A compound measure of parental dental
      health behavior was applied in logistic regression analyses. The results showed
      that there were statistically significant associations of use of dental floss,
      tooth brushing, and drinking of non-sugared mineral water among parents and their
      adolescent offspring. No significant gender interaction in the association
      between same- or different-sex parent-adolescent dyads was observed. These
      findings indicate that parents function as social models for their offspring well
      into the adolescent period with regard to several dental health behaviors.

PMID- 8876735
TI  - Dental health in 14- to 17-year-old Estonian schoolchildren in Tartu and Tallinn.
AB  - The dental health of 392 Estonian schoolchildren aged 14-17 years (197 in Tartu
      and 195 in Tallinn) was studied. In Tartu only 1 child had lost teeth because of
      caries, as against 30 in Tallinn. Clinically caries-free dentitions were found in
      15% of the children in Tartu and in 3% in Tallinn. The mean DMFT value was 3.7 in
      Tartu and 7.0 in Tallinn, being higher among girls in both cities. The mean DT
      value was 1.0 in Tartu and 2.6 in Tallinn. All subjects examined had a gingival
      bleeding index (GBI) higher than zero. The mean GBI was 20% in Tartu and 18% in
      Tallinn.

PMID- 8876736
TI  - Prevalence of gingivitis in 6-year-olds in Reykjavik, Iceland.
AB  - As part of a wider investigation of malocclusion, the aim of this study was to
      determine the prevalence of gingivitis in 6-year-olds in Reykjavik. Parents and
      guardians of the 401 children in 8 schools were invited by letter to have their
      children take part. There were 230 positive replies (57%). The Gingival Bleeding
      Index was used to determine the condition of the gingiva on mesiobuccal and
      buccal surfaces of 6 selected teeth (totaling 12 surfaces). The results showed
      that 26% had healthy gingivae, 23% showed bleeding from one surface, 20% from
      two, 17% from three, and 15% from four to eight surfaces. There were no
      statistically significant differences in the number of bleeding surfaces between
      boys and girls. The mean GBI for the whole group was 16%. Gingivitis in this
      group was therefore prevalent but usually slight.

PMID- 8876737
TI  - Caries prevalence and associated predisposing conditions in recently hospitalized
      elderly persons.
AB  - The prevalence of caries and caries risk factors was studied among 120
      consecutively hospitalized elderly persons. Coronal caries was recorded using the
      WHO criteria, and active and inactive root caries in accordance with Fejerskov et
      al. The CPITN was used to evaluate the periodontal state and plaque accumulation
      in accordance with Loe & Silness. Of the 1212 teeth examined 5% had active
      coronal caries (2% inactive), 14% active root caries (2% inactive), and 10%
      fillings with recurrent caries. No relationship was found between caries
      prevalence, degree of dependence, number of medicaments, age, and gender.
      Patients with psychiatric diseases had increased caries prevalence (P < 0.01),
      and lower caries prevalence was associated with frequent tooth brushing (P <
      0.05). At the tooth level root caries was associated with high plaque scores (P <
      0.001), degree of gingival recession (P < 0.001), presence of coronal caries (P <
      0.001), and increased pocket depth (P < 0.01). The results strongly indicate that
      oral hygiene measures should be introduced immediately after hospitalization of
      these patients.

PMID- 8876738
TI  - Prevalence of some oral complaints and their relation to oral health variables in
      an adult Swedish population.
AB  - The aim of the study was to determine, in a randomly selected 20- to 70-year-old
      Swedish population, the prevalence of oral burning sensations and taste
      disturbances and their possible correlation to salivary factors, the presence of
      mandibular dysfunction, the prevalence of teeth, restorative procedures, caries
      and periodontal disease, and smoking habits. Of a total of 533 dentate
      individuals, 112 reported a total of 139 symptoms. Eleven of the 40 edentulous
      individuals reported a total of 14 symptoms. Burning sensations were reported by
      18 (3.4%) of the dentate and 1 (2.5%) of the edentulous individuals. The symptoms
      of pricking and burning were significantly correlated to mandibular dysfunction
      and negatively correlated to the number of teeth. The symptom of bad taste was
      correlated to the number of amalgam-filled surfaces and to cigarette smoking. No
      other statistically significant correlation could be found.

PMID- 8876739
TI  - Incisal and occlusal tooth wear in children and adolescents in a Swedish
      population.
AB  - The material consisted of 527 randomly selected children and adolescents from the
      community of Jonkoping, Sweden, who in 1983 reached the age of 3, 5, 10, 15, or
      20 years. The degree of incisal or occlusal tooth wear was evaluated for each
      single tooth in accordance with the following criteria: score 0 = no wear or
      negligible wear of enamel; score 1 = obvious wear of enamel or wear through the
      enamel to the dentin in single spots; score 2 = wear of the dentin up to one
      third of the crown height; and score 3 = wear of the dentin more than one-third
      of the crown height. In the age groups 3 and 5 years the primary dentition was
      studied, and in the age groups 10, 15, and 20 years the permanent dentition. In
      the 3-year-old children 63% and in the 5-year-olds 19% had no or slight incisal
      or occlusal wear in the primary dentition. In the permanent dentition the
      corresponding figures for the 10-, 15-, and 20-year-olds were 78%, 51%, and 35%,
      respectively. The 5-year-olds had the highest percentage of primary teeth with
      incisal or occlusal wear related to existing teeth in accordance with criteria 1
      3 (32.2%), and the 10-year-olds had the lowest score for permanent teeth (2.5%).
      There were small or no differences in tooth wear between the sexes in these age
      groups. Eighteen children (17%) among the 5-year-olds had one or more teeth with
      wear scored 2 in the primary dentition, and one individual had 4 primary teeth
      scored 3. The corresponding figures for the 3-, 10-, 15-, and 20 year-olds were
      2%, 1%, 7% and 6%, respectively. No permanent teeth with wear scored 3 were found
      in these age groups. The number of teeth with incisal or occlusal wear increased
      with age both in the primary and in the permanent dentition.

PMID- 8876740
TI  - Signs and symptoms of temporomandibular disorders in adolescent violin players.
AB  - Signs and symptoms of temporomandibular disorders (TMDs) and the frequency of
      radiologically observed abnormalities in the condyles of temporomandibular joints
      (TMJs) of adolescent violin players (VP group) were investigated in a group of 31
      music students and in their age- and sex-matched controls (C group). All subjects
      underwent a routine clinical stomatognathic examination, a standardized
      interview, and radiography of the condyles. The VP group reported a higher
      frequency of the subjective symptoms: pain in the TMJ when chewing, a feeling of
      stiffness in the TMJ, and clenching of the teeth. Clinically, the VP group showed
      a greater range of maximal protrusion and of maximal laterotrusion to the right,
      and a greater frequency of deviation to the right on opening. They also showed
      more palpatory tenderness in the masticatory muscles and pain in the TMJ on
      maximal opening. The number of playing years and the number of weekly playing
      hours correlated with several signs and symptoms of TMDs. In terms of radiologic
      findings in the condyles of the TMJs there was no difference between the groups.
      It is concluded that intense violin playing may have a predisposing role in the
      etiology of TMDs in adolescence.

PMID- 8876741
TI  - Studies on cutaneous blood flow in the mammary gland of lactating rats.
AB  - The mechanisms that regulate mammary blood flow during lactation are not fully
      understood. In the present study laser Doppler flowmetry (LDF) was used to
      measure blood flow in the cutaneous microvessels of the mammary gland of
      lactating rats. The effects of suckling on blood flow were examined, as were
      those of local injection of oxytocin (0.5-5 mU) and the vasoactive peptides
      calcitonin gene-related peptide (CGRP; 0.1-10 pmol), vasoactive intestinal
      polypeptide (VIP; 0.4-20 pmol) and neuropeptide Y (NPY; 1-40 pmol). Blood flow
      responses to suckling varied depending on how much time had lapsed since the
      previous suckling. In rats with milk in the gland, suckling caused an initial
      increase in blood flow. In connection with milk let-down, the blood flow
      decreased, but was followed by a second increase. In recently suckled rats with
      no milk in the gland the increase in blood flow corresponded to the number of
      pups suckling. Oxytocin injections also had varying effects on mammary blood flow
      depending on how recently suckling had taken place. In non-suckled rats with milk
      in the gland, oxytocin injections caused a rise in blood flow that was
      interrupted by a fall during milk ejection. In recently suckled rats, all doses
      of oxytocin caused an increase in blood flow of similar magnitude. However, the
      effect of the higher doses had a longer duration. CGRP and VIP injections caused
      a dose-dependent increase in mammary blood flow regardless of when suckling last
      occurred. NPY injections caused a dose-dependent decrease in blood flow.

PMID- 8876742
TI  - Sustained forearm vasodilation in humans during mental stress is not
      neurogenically mediated.
AB  - To evaluate the possible neurogenic influence on forearm vasodilation during
      mental stress (Stroop's colour word conflict test), haemodynamic and
      catecholamine responses were registered in 12 healthy men after axillary
      blockade. Forearm blood flow was measured with venous occlusion plethysmography
      and forearm vascular resistance was calculated, with intraarterial blood pressure
      data. Blood samples for arterial and venous adrenaline and noradrenaline
      determinations were collected. Basal forearm blood flow increased markedly after
      axillary blockade, but the relative responses of forearm blood flow and forearm
      vascular resistance to mental stress were the same as in previously studied
      unblocked individuals (about +125% and about -40%, respectively). There was no
      increase in noradrenaline overflow from the forearm during mental stress in the
      nerve blocked arm. Heart rate and arterial systolic pressure responses as well as
      catecholamine responses to mental stress were augmented in the nerve blocked
      group, presumably due to a certain arousal caused by the experimental procedure.
      Increases in forearm blood flow and decreases in forearm vascular resistance
      during infusion of adrenaline were similar in the nerve blocked and in the
      control arm. In conclusion, vasodilation in the forearm during mental stress
      occurs in the absence of nervous control of the vascular bed. The reactivity of
      the vascular bed to an exogenous vasodilator (adrenaline) remains unchanged after
      axillary blockade.

PMID- 8876743
TI  - Ageing reduces sympatho-suppressive response to head-out water immersion in
      humans.
AB  - Muscle sympathetic nerve activity (MSNA) is suppressed during thermoneutral head
      out water immersion (HOI) in humans. In this study, the effects of ageing on the
      suppressive response of MSNA to HOI were determined. MSNA was recorded
      microneurographically from the tibial nerve in 16 healthy men, 10 of whom were
      aged 19-30 years (young group) and six aged 45-67 years (older group). MSNA was
      suppressed in all the subjects during HOI. The suppressive response was
      significantly less prominent in the older group than in the young group. A
      significant negative correlation between age and the suppressive response of MSNA
      induced by HOI (r = -0.53, P < 0.05) was found. We conclude that suppressive
      response of sympathetic nerve activity to HOI is reduced with age.

PMID- 8876744
TI  - The effects of hexamethonium on cerebral blood flow and cerebral function during
      relative cerebral ischaemia in rats.
AB  - Cerebral blood flow in either the cortex, thalamic region or the brain stem, as
      well as somatosensory evoked potentials were measured in a model of moderate
      cerebral ischaemia in three groups of anaesthetized spontaneously hypertensive
      rats. The rats were bled to reduce evoked potential amplitudes to approximately
      50-60% of pre-haemorrhage control. The consequent blood pressure fall reduced
      blood flow to approximately 65, 80 and 85% of pre-haemorrhage control in the
      cortical, thalamic and brain stem regions, respectively, as measured with a laser
      Doppler flowmeter. Hexamethonium (10 mg kg-1 i.v.), an autonomic ganglion
      blocker, caused vasodilation and a slight (7-13 units of prebleeding control)
      increase in blood flow in all the three regions, and the somatosensory evoked
      potentials normalized. In addition, the latency of the first evoked potential
      component decreased toward prebleeding values. Heart rate decreased and a
      transient decrease was also observed in mean arterial pressure despite an attempt
      to keep it constant with a pressure regulating reservoir. It is possible that the
      slightly increased regional cerebral blood flow after hexamethonium injection can
      explain the improved cerebral function as indicated by the enhanced somatosensory
      evoked potentials. However, the results might also indicate an autonomic
      regulation of afferent sensory pathways.

PMID- 8876745
TI  - Effects of angiotensin-converting enzyme inhibition on arterial, venous and
      capillary functions in cat skeletal muscle in vivo.
AB  - The aim of the present study was to analyse quantitatively, on a cat
      gastrocnemius muscle preparation in vivo, the effects of local angiotensin
      converting enzyme (ACE) inhibition by enalaprilat on total regional vascular
      resistance (tone) and its distribution to the large-bore arterial resistance
      vessels (> 25 microns), the small arterioles (< 25 microns) and the veins.
      Associated effects on capillary pressure and fluid exchange were also studied.
      Close-arterial infusion of enalaprilat (0.05-0.20 mg kg muscle tissue min-1)
      elicited a moderate dilator response in all three consecutive sections of the
      muscle vascular bed, an increase in capillary pressure and transcapillary fluid
      filtration. This dilation could be abolished by the selective bradykinin B2
      receptor antagonist Hoe 140 (2 mg kg-1 min-1, i.a.), indicating that the dilator
      mechanism of ACE inhibition was an increased local concentration of bradykinin,
      and hardly at all a decreased concentration of angiotensin (AT) II. The
      generalized dilator response to ACE inhibition along the vascular bed suggested a
      relatively uniform distribution of ACE from artery to vein and this was further
      supported by the finding that a close-arterial infusion of AT I (0.04-0.32
      microgram kg-1 min-1), which was vasoactive only after conversion to AT II by
      local ACE, elicited a generalized constrictor response in all three vascular
      sections. In contrast, infused AT II (0.01-0.16 microgram kg-1 min-1) constricted
      almost selectively the large-bore arterial vessels. The specific angiotensin AT1
      receptor antagonist losartan (2 mg kg-1 min-1, i.a.) abolished the constrictor
      response to AT II but did not affect vascular tone under control conditions,
      indicating that AT II is not involved in the initiation of basal vascular tone in
      muscle. These results, taken together, indicate that under basal conditions
      vascular ACE contributes to the local control of vascular tone in skeletal muscle
      by degrading the endogenous dilator bradykinin, and not by converting AT I into
      vasoconstrictor AT II.

PMID- 8876746
TI  - High afterload during 10 min of regional ischaemia affects diastolic creep but
      not systolic function in reperfused (stunned) myocardium.
AB  - The effect of afterload during regional ischaemia on myocardial stunning was
      studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left
      anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload
      was decreased by intravenous infusion of nitroglycerine 3-8 micrograms kg-1 min-1
      in group I (n = 8); left ventricular peak systolic pressure (LVSP) 84 +/- 4 mmHg
      (mean +/- SEM) during coronary artery occlusion. In group II (n = 7) LVSP was
      increased to 188 +/- 10 mmHg by inflating an intraaortic balloon during coronary
      artery occlusion. Regional function in the LAD perfused region was evaluated by
      cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by
      radio-labelled microspheres. Afterload alterations did not affect regional
      systolic shortening (10.8 +/- 2.0% vs. 11.0 +/- 1.5% in group I and II,
      respectively, after 60 min of reperfusion). However, increased end-diastolic
      dimensions (diastolic creep) in both the circumferential and longitudinal
      segments were markedly more pronounced in the high afterload group (group II).
      Also important, the markedly increased myocardial tissue blood flow during
      reperfusion in group II as compared with group I (2.30 +/- 0.18 vs. 1.34 +/- 0.08
      mL min-1 g-1 and 2.58 +/- 0.23 vs. 1.49 +/- 0.07 mL min-1 g-1 in subepicardial
      and subendocardial layers in the LAD perfused region) suggests that increased
      diastolic creep increased metabolic demands. This study indicates that passive
      stretching of the ischaemic area during coronary artery occlusion is an important
      mechanism behind diastolic creep.

PMID- 8876747
TI  - Comparative study of the effects of nitric oxide synthase and cyclo-oxygenase
      inhibition on duodenal functions in rats anaesthetized with inactin, urethane or
      alpha-chloralose.
AB  - This study was undertaken to investigate the effects of a cyclo-oxygenase and a
      nitric oxide synthase (NOS) inhibitor on duodenal mucosal alkaline secretion
      (DMAS), motility and mucosal permeability in inactin-, urethane- and alpha
      chloralose anaesthetized rats. Proximal duodenum was perfused with a 150 mM NaCl
      solution and DMAS was determined by back titration. Mucosal permeability was
      assessed by measuring blood to lumen clearance of 51Cr-EDTA and duodenal motility
      by measuring intraluminal pressure. Mean arterial blood pressure and mucosal
      permeability were significantly lower in urethane- than in inactin- or alpha
      chloralose anaesthetized rats (urethane: 90 +/- 2 mm Hg and 0.15 +/- 0.02 mL min
      1 100 g-1; inactin: 112 +/- 5 mm Hg and 0.62 +/- 0.15 mL min-1 100 g-1; alpha
      chloralose: 111 +/- 4 mm Hg and 0.61 +/- 0.06 mL min-1 100 g-1, respectively).
      Basal (pre-drug) DMAS was significantly lower in urethane rats (6.2 +/- 1.0 mumol
      cm-1 h-1) than in alpha-chloralose (9.3 +/- 1.2 mumol cm-1 h-1), but not
      different from that in inactin-anaesthetized rats (7.5 +/- 0.8 mumol cm-1 h-1).
      No or very few spontaneous duodenal contractions occurred under the control (pre
      drug) conditions in any group. All animals responded to the cyclo-oxygenase
      inhibitor indomethacin or the NOS inhibitor N-nitro-L-arginine-methyl-ester (L
      NAME) with induction of duodenal motility and an increase in DMAS. The effect of
      indomethacin or L-NAME on mucosal permeability was similar in all anaesthetic
      groups except that L-NAME induced a transient increase in the inactin and alpha
      chloralose groups but a sustained increase in urethane-anaesthetized animals. It
      is concluded that inactin- and alpha-chloralose anaesthetized rats do not differ
      regarding the studied basal values. Urethane-anaesthetized animals differed from
      rats given the other two anaesthetics in that basal mucosal permeability and mean
      arterial blood pressure were lower. Endogenous prostaglandins and NO contribute
      to the postoperative ileus and the low rate of DMAS also in urethane- and alpha
      chloralose.

PMID- 8876748
TI  - Characteristics of fasting and fed myoelectric activity in rat small intestine:
      evaluation by computer analysis.
AB  - Evaluation of gastrointestinal myoelectric activity has been limited by the
      assessment techniques and the complexity of the recorded myoelectric signal.
      Commonly, myoelectric activity is evaluated as motor patterns, which only gives a
      semiquantitative measure of myoelectric events within the bowel wall. Using
      myoelectric recordings from the proximal small intestine in rats, a computerized
      system for acquisition, storage, display and calculation of characteristics for
      the myoelectric activity was developed. The software was tested in myoelectric
      recordings from nine rats in fasting and fed states. All migrating myoelectric
      complexes (MMCs) during fasting and fed myoelectric patterns were recognized in
      both digital and analog recordings. Reproduction of myoelectric recordings by the
      computerized system was indistinguishable from that of the analog system.
      Employing an appropriate cut-off trigger level and a high sampling frequency,
      spike potentials were recorded in the proximal jejunum with 0.4 (0.3-0.5) spikes
      10 s-1 during phase 1 of MMC, 19.5 (15.1-23.9) (P < 0.001) during phase 2, and
      103.8 (97.2-110.5) (P < 0.001) during phase 3. In fasted state, MMCs were most
      frequent in the proximal jejunum whereas fewer were found in the duodenum and
      distal jejunum. To achieve stable values for MMC cycle length at least four MMCs
      had to be calculated. After feeding in phase 1, the myoelectric activity
      increased to 23.8 (13.6-33.9) spikes 10 s-1 (P < 0.001), whereafter the spiking
      activity decreased over a period of 2 h until a fasting motor pattern was
      resumed. It is concluded that computerized technology enables evaluation not only
      of myoelectric patterns, but also of spiking activity per time unit, i.e. the
      intensity of myoelectric activity in the gut.

PMID- 8876749
TI  - Pancreastatin modulates glucose-stimulated insulin secretion from the perfused
      rat pancreas.
AB  - Pancreastatin is known to be produced in islet B cells and to inhibit insulin
      secretion. In this study, we examined whether the peptide affects insulin
      secretion from the perfused rat pancreas during raising or lowering the glucose
      concentration within the physiological range. We found that synthetic porcine
      pancreastatin (15 nmol L-1) significantly inhibited the first phase (5 min) of
      insulin release induced by raising the glucose concentration from 4.2 to 8.3 mmol
      L-1 (P < 0.05) without affecting the second phase. Furthermore, the fall in
      insulin secretion induced by lowering the glucose concentration from 8.3 to 5.5
      mmol L-1 was significantly exaggerated in presence of pancreastatin during the
      first 5 min (P < 0.05). In contrast, pancreastatin did not affect the inhibition
      of insulin secretion induced by either the alpha 2-adrenoceptor agonist,
      clonidine (2 nmol L-1), or the P1-purinoceptor (A1-subtype) agonist, N6 (+)
      phenylisopropyladenosine (D-PIA) (1.65 mumol L-1). In conclusion, our results
      show that pancreastatin is a modulator of the early changes in insulin secretion
      after increase or decrease of the glucose concentration within the physiological
      range. This suggests that pancreastatin is a modulator of glucose-stimulated
      insulin secretion.

PMID- 8876750
TI  - Perchlorate is hypoglycaemic by amplifying glucose-stimulated insulin secretion
      in mice.
AB  - The chaotropic anion perchlorate (ClO4-) is a potent amplifier of stimulated
      insulin secretion in vitro. Acute effects of perchlorate on serum glucose and
      insulin levels were investigated in normal mice. Intraperitoneal injection of
      single doses of NaClO4 at 10-300 mg kg-1 body wt showed only a slight, reducing
      effect on the basal serum glucose level, reaching statistical significance only
      at 300 mg kg-1 body wt. However, a single dose of NaClO4 (300 mg kg-1 body wt)
      given together with a glucose load (0.9 g kg-1 body wt) significantly
      counteracted the increase in serum glucose and reduced the serum glucose/insulin
      ratio 20 min after administration. The perchlorate effect was transient and at 60
      and 90 min after administration the serum insulin and glucose levels were
      comparable with those of the glucose-treated control animals. The results suggest
      that perchlorate enhances glucose-stimulated insulin secretion in mice in vivo
      and thereby reduces the serum glucose level after a glucose load but does not
      much affect the basal serum glucose level.

PMID- 8876751
TI  - Neuromuscular adaptations during bilateral versus unilateral strength training in
      middle-aged and elderly men and women.
AB  - Twelve middle-aged men and 12 middle-aged women in the 50-year-old age group
      (M50; range 44-57 years; W50; 43-57), and 12 elderly men and 12 elderly women in
      the 70-year-old age group (M70; 59-75; W70; 62-75) volunteered as subjects in
      order to examine effects of 12-week progressive heavy resistance strength
      training on electromyographic activity (EMG), muscle cross-sectional area (CSA)
      of the quadriceps femoris and maximal concentric force in a one repetition
      maximum (1 RM) test of the knee extensor muscles. One half of the subjects in
      each group performed the knee extension (and flexion) exercises only bilaterally
      (BIL), while another half performed the exercises only unilaterally (UNIL). None
      of the subject groups demonstrated statistically significant changes in any of
      the 1 RM values during the 2 week control period with no training (between week 
      2 and 0) preceding the actual experimental training. However, the 12-week
      training resulted in increases (P < 0.05-0.001) in 1 RM values in each group so
      that the average relative increase of 19 +/- 12% (P < 0.001) in bilateral 1 RM in
      all BIL trained subjects was greater (P < 0.05) than that of 13 +/- 8% (P <
      0.001) recorded for all UNIL trained subjects. The average relative increases of
      17 +/- 11% (P < 0.001) and 14 +/- 14% (P < 0.001) in unilateral 1 RM values of
      the right and left leg in all UNIL trained subjects were greater (P < 0.05) than
      those of 10 +/- 18% (P < 0.001) and 11 +/- 11% (P < 0.001) recorded for all BIL
      trained subjects, respectively. The relative average increase of 19 +/- 19% (P <
      0.001) observed in the maximum averaged IEMG of both legs during the bilateral
      actions in all BIL trained subjects was greater (P < 0.05) than that of 10 +/-
      17% (P < 0.05) recorded for all UNIL trained subjects. The relative increases of
      14 +/- 12% (P < 0.001) and 11 +/- 6% (P < 0.001) recorded for the CSA in all BIL
      and UNIL trained subjects did not differ significantly from each others. The
      present findings suggest that progressive heavy resistance strength training
      leads to great increases in maximal dynamic strength of the trained subjects
      accompanied by both considerable neural adaptations and muscular hypertrophy not
      only in middle-aged but also in elderly men and women. Both bilateral and
      unilateral exercises are effective to produce functional and structural
      adaptations in the neuromuscular system, although the magnitude of functional
      strength increase seems to be specific to the type of exercise used, further
      supporting the principle of specificity in the design of strength programmes.

PMID- 8876752
TI  - Changes in fibre types in rat soleus and plantaris muscles following
      hypophysectomy and compensatory overload.
AB  - We investigated whether hypophysectomy could modify the change in muscle fibre
      types caused by compensatory overload. Male Wistar strain rats were assigned to
      groups of either normal control (NC), hypophysectomized control (HC), normal
      compensatory overloaded (NO), or hypophysectomized compensatory overloaded (HO).
      Compensatory overload was induced by the bilateral removal of the gastrocnemius
      muscle. Five weeks later, there were losses in the soleus and plantaris muscle
      weights as a result of hypophysectomy. Compensatory overload increased muscle
      weights independently of the hypophysectomy. Growth hormone and 3,5,3'
      triiodothyronine levels were significantly decreased following hypophysectomy. In
      the soleus, hypophysectomy increased the percentage of type I fibres at the
      expense of type IIA fibres. Compensatory overload decreased type IIA fibres under
      the hypophysectomized condition. In the plantaris, the percentage of type IIC
      fibres was increased at the expense of both type IIA and IIB fibres following
      hypophysectomy. The decrease in type IIB fibres cause by compensatory overload
      was induced irrespective of hypophysectomy. The changes in muscle fibre types in
      the HO group were equal to the sum of the changes in the HC and NO groups. These
      results suggest that after a period of 5 weeks hypophysectomy may induced
      decrease in type IIA and IIB fibres in association with the lack of pituitary and
      thyroid hormones, and that the hypophysectomy could not modify the change in
      muscle fibre types caused by compensatory overload.

PMID- 8876754
TI  - 1 alpha,25-dihydroxyvitamin D3 stimulated alkaline phosphatase activity in
      cultured pig kidney epithelial LLC-PK1 cells.
AB  - The effects of 1 alpha,25-dihydroxyvitamin D3 (1,25 (OH)2D3) and human growth
      hormone (hGH) on the activity of alkaline phosphatase (ALP) were evaluated in pig
      kidney LLC-PK1 cultured cells. 1,25(OH)2D3 (10(-9)-10(-6) mol L-1) and hGH (10(
      7) mol L-1) increased ALP activity in these cells while no hormonal effect was
      detected on two other enzyme activities: gamma-glutamyl transferase and acid
      phosphatase. ALP activity was maximally increased after 4.5-6 h incubation with
      both hormones. The hormonal induction of ALP activity was prevented by a
      pretreatment of cells with actinomycin D. Thus, 1,25 (OH)2D3 and may be hGH could
      stimulate ALP activity via a transcription of some gene.

PMID- 8876753
TI  - Neuropeptide Y regulates rat renal tubular Na,K-ATPase through several signalling
      pathways.
AB  - Neuropeptide Y (NPY) has at least three receptors (Y1, Y2, and Y3) through which
      it influences different mechanisms in many cell types. Previous data suggest that
      the Y2 receptor may be divided into prejunctional and postjunctional subgroups.
      We have examined the intracellular signalling pathways of the postjunctional Y2
      receptor in rat renal proximal tubules. The results indicate that NPY regulates
      Na+,K(+)-ATPase through several signalling pathways: (1) In proximal tubule (PT)
      cells NPY increased intracellular calcium. The response was blocked by removing
      extracellular calcium and was also blocked by using nifedipine. This suggests
      that calcium was increased by influx from the extracellular space through L-type
      calcium channels. (2) NPY increased Na+,K(+)-ATPase activity in PT segments and
      this effect was also blocked by nifedipine. CaMKII-Ala286[281-302] a blocker of
      Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibited the NPY-stimulated
      Na+,K(+)-ATPase activity. This implies that increased intracellular calcium
      activates CaMKII which subsequently increases Na+,K(+)-ATPase activity. CaMKII
      thus appear to act similar to what has been proposed for protein phosphatase 2B.
      (3) Calphostin C, an inhibitor of protein kinase C (PKC), did not inhibit NPY
      stimulated Na+,K(+)-ATPase activity. PKC is, therefore, unlikely to be involved.
      (4) Y2 receptors are negatively coupled to the cAMP pathway. NPY attenuated
      forskolin-stimulated cAMP production in renal tubules and exogenous cAMP
      counteracted the NPY-stimulated Na+,K(+)-ATPase activity. This illustrated the
      importance of NPY for the regulation of renal sodium handling. We also propose
      that the renal tubule cell is a good model for studying the function and
      mechanisms of postjunctional Y2 receptors.

PMID- 8876755
TI  - Airborne nitric oxide: inflammatory marker and aerocrine messenger in man.
AB  - 1. In healthy subjects, exhaled NO originates mainly from the upper airways with
      only a minor contribution from the lower airways and the lungs. A large NO
      production takes place in the epithelium of the paranasal sinuses and this NO
      contributes considerably to the levels of NO found in nasally exhaled air.
      Immunohistochemical and mRNA in situ hybridisation studies suggest that sinus NO
      synthase is identical or very closely related to the human iNOS. Furthermore, the
      NOS activity in sinus mucosa is mostly Ca(2+)-independent. However, the
      regulation of sinus NOS expression seems to differ fundamentally from what has
      earlier been described for iNOS. Thus, sinus NOS is constitutively expressed and
      seems resistant to steroids. The high local NO concentrations in the nasal
      airways and the sinuses may help to protect against airborne infectious agents.
      Thus, airborne NO may represent the very first line of defence in the airways,
      possibly acting on pathogens even before they reach the mucosa. 2. Nasal
      concentrations of NO are markedly reduced in children with Kartagener's syndrome
      and in patients with CF. A simple chemiluminescence test test could be of help in
      early non-invasive diagnosis of these chronic airway diseases. 3. Inhaled
      endogenous NO, derived from the upper airways, may be involved in regulation of
      pulmonary function in man. NO will reach the lower airways and the lungs with the
      inspired air and at levels that are especially high during nasal breathing. This
      NO may act by enhancing blood flow preferentially in well ventilated areas of the
      lung, thus optimizing ventilation/perfusion matching. The involvement of
      autogenous NO in regulation of pulmonary function may represent a novel
      physiological principle, namely that of an enzymatically produced airborne
      messenger. The term "aerocrine" may be appropriate for this action of NO in the
      airways. These findings may also help to explain one biological role of the
      enigmatic human paranasal sinuses, the major sources of NO in the upper airways.
      4. A continuous production of NO takes place in the acidic stomach through
      chemical reduction of nitrite present in swallowed saliva. This is the first
      evidence of non-enzymatic NO production in humans. Stomach NO may be involved in
      local defence against swallowed pathogens and in regulation of superficial
      mucosal blood flow and mucus production. 5. Luminal concentrations of NO are
      increased in the lower airways of asthmatic children, in the colon of patients
      with inflammatory bowel disease, and in the urinary bladder of patients with
      cystitis. Local steroid treatment reduces orally exhaled NO levels in asthmatic
      children. Nasal NO levels did not differ between controls and asthmatic children
      with or without concomitant allergic rhinitis. In conclusion, nitric oxide found
      in exhaled air originates mainly in the upper airways. A large production of NO
      takes place in the paranasal sinuses from a constitutively-expressed, steroid
      resistant "inducible-like" NO synthase in the epithelial cells. Sinus NO
      contributes substantially to levels of NO found in nasally exhaled air. Sinus NO
      may have a dual function. First, the very high concentrations in the sinuses may
      contribute to local host defence. Second, when diluted in the inhaled air, sinus
      derived NO may act as an "aerocrine" messenger, with distal effects on pulmonary
      blood flow and oxygen uptake. Intubated patients are deprived of autogenous NO
      from the upper airways and might benefit from substitution. Measurements of local
      NO production in hollow organs may be done easily by analysing the concentrations
      of NO gas in luminal air. Such noninvasive methods may be useful not only to
      explore the role of NO in inflammation and host defence, but also in the
      diagnosis and monitoring of inflammatory mucosal diseases such as asthma,
      ulcerative colitis and cystitis. Thus, airborne NO may be looked upon as a marker
      of inflammation and as an aerocrine messenger in humans.

PMID- 8876756
TI  - Quantitative sensory examination of epidural anaesthesia and analgesia in man.

PMID- 8876757
TI  - Illness severity and self-efficacy as course predictors of DSM-IV alcohol
      dependence in a multisite clinical sample.
AB  - Illness severity and self-efficacy are two constructs of growing interest as
      predictors of clinical response in alcoholism. Using alternative measures of
      illness severity (DSM-IV symptom count, Alcohol Dependence Scale, and Addiction
      Severity Index) and self-efficacy (brief version of the Situational Confidence
      Questionnaire) rigorously controlled for theoretically important background
      variables, we studied their unique contribution to multiple indices of relapse,
      relapse latency, and use of alternative coping behaviors in a large,
      heterogeneous clinical sample. The Alcohol Dependence Scale contributed to the
      prediction of 4 of 5 relapse indicators. The SCQ failed to predict relapse
      behavior or its precursor, coping response. The findings emphasize the predictive
      validity of severity of dependence as a course specifier and underline the need
      for more sensitive and externally valid measures of cognitive processes such as
      self-efficacy for application in future studies of posttreatment behavior.

PMID- 8876758
TI  - A criterion measurement model for health behavior change.
AB  - Researchers in the field of health behavior change have traditionally relied on a
      univariate criterion measure to evaluate the efficacy of an intervention. Such
      measures have superficial face validity but suffer from a number of problems: (a)
      lack of precise definitions; (b) poor statistical power; and (c) a lack of
      meaningfulness for some aspects of the problem. As an alternative, a theoretical
      model is developed that attempts to define more appropriate multivariate sets of
      dependent variables for the study of health behavior change. The model involves
      three separate constructs: Positive Evaluation Strength, Negative Evaluation
      Strength, and Habit Strength. The pattern of change for each construct is
      described across four stages of change: Precontemplation, Contemplation, Action,
      and Maintenance. For each construct, two thresholds are proposed representing the
      ability of the environment to modify the construct. Four tests of the model are
      provided from existing data sets. First, a structural model analysis was used to
      test if the proposed measurement model adequately fits the data. Second, a
      dynamic typology approach produced profiles of change that are consistent with
      the model. Third, a time series analysis provided support for the assumed model.
      Fourth, longitudinal, five-wave panel design was employed to test if the relation
      between the two cognitive variables (Pros and Cons) and the behavioral measure
      (Habit Strength) was consistent with the model. Implications for alternative
      intervention strategies are discussed.

PMID- 8876759
TI  - Measurement of alcohol and tobacco availability to underage students.
AB  - Communities Mobilizing for Change on Alcohol (CMCA) and Tobacco Policy Options
      for Prevention (TPOP) are randomized multicommunity trials designed to reduce the
      availability of alcohol (CMCA) and tobacco (TPOP) products to underage youth. We
      assessed the test-retest reliability and internal consistency of perceived
      availability measures developed for surveys of middle and high school students.
      Two questionnaires were administered twice, each to separate student populations
      (CMCA: 9th graders; TPOP; 8th graders) 21 to 26 days apart. A total of 111 (CMCA)
      and 70 (TPOP) subjects participated at both times (participation rate of 93.3%
      and 84.3%, respectively). There were no statistically significant differences in
      the distribution of demographic variables, alcohol or tobacco use variables, or
      availability variables across administrations. The scales assessing perceived
      access to alcohol or tobacco had high internal consistency (Cronbach's alpha of
      0.84 for alcohol and 0.77 for tobacco), but moderate to low test-retest
      correlations (0.58 and 0.13, respectively). Single-item measures of sources of
      alcohol and tobacco and reported buy attempts also had moderate to low test
      retest correlates (0.10-0.65). We recommend that items assessing tobacco and
      alcohol availability to underage youth be further developed.

PMID- 8876760
TI  - Mediators of drug treatment outcomes.
AB  - Treatment for drug use, like the process by which a person comes to use illicit
      drugs, may be seen to be at least in part a psychosocial process involving
      emotional, cognitive, and relationship domains. Treatment programs attempt to
      improve the psychosocial functioning of clients with the ultimate goal of
      effecting change in drug-use behaviors. In a longitudinal study of clients in an
      intensive outpatient treatment program using a cognitive behavioral model to
      treat crack cocaine use, it was found that length of treatment was directly
      associated with improvement in emotional well-being, cognitive functioning, and
      relationships. Of the three psychosocial domains, improvement in relationships
      had the strongest effect on self-reported decreases in cocaine usage, verified by
      urinalysis. Improvement in cognitive functioning had a small impact on cocaine
      use, whereas improvement in emotional well-being had almost no independent effect
      in this cognitive behavioral treatment program.

PMID- 8876761
TI  - Perception of friends' use of alcohol, cigarettes, and marijuana among urban
      schoolchildren: a longitudinal analysis.
AB  - Relations between adolescents' substance use and perceptions of their friends'
      substance use were examined cross-sectionally and longitudinally in a
      predominantly African-American school district. Fourth- and fifth-grade students
      were surveyed and tracked for 4 consecutive years. Cross-sectional samples
      included 3,073, 5,955, 7,701, and 6,616 students in years 1 to 4, respectively;
      the longitudinal sample included 1,802 students surveyed in every year. Self
      reported substance use of friends and classmates also was assessed. Perceived
      friends' substance use had a stronger association with prior substance use than
      friends' self-reported substance use in every year. Perceived family use and
      classmates' self-reported use also made independent contributions to regression
      models. Longitudinal structural equation analyses indicated that perceived
      friends' use is more likely to be a product of an adolescent's previous substance
      use than a precursor of subsequent substance use. The findings contradict
      prevailing theories on the influence of peers on substance use.

PMID- 8876762
TI  - The relationship of social context of drinking, perceived social norms, and
      parental influence to various drinking patterns of adolescents.
AB  - An anonymous questionnaire was administered to a sample of over 890 adolescent
      drinkers. The questionnaire contained measures of their social context of
      drinking, perceived social norms, and perceived parental behaviors regarding
      drinking. These measures were related to a variety of alcohol problem behaviors
      including binge drinking, driving while alcohol-impaired, riding with an alcohol
      impaired driver, and experiencing one or more negative consequences because of
      drinking. Results indicated that drinking frequently in a social context of
      social facilitation, stress control or school defiance, as well as having close
      friends engage in these behaviors, tended to separate alcohol abusers from
      nonabusers. The implications for program development are discussed.

PMID- 8876763
TI  - The impact of behavior and addiction on psychological models of cigarette and
      alcohol use during pregnancy.
AB  - This prospective study of 241 women investigated the impact of past behavior and
      psychological factors on cigarette and alcohol use during pregnancy. Smokers'
      cigarette use was compared with their alcohol consumption during pregnancy, and
      drinking among smokers was compared with that of nonsmokers. Only prior smoking
      directly predicted smokers' cigarette use later in pregnancy, whereas smokers'
      alcohol use was related to both their previous drinking and their drinking self
      efficacy. Among nonsmokers, neither drinking before nor early in pregnancy was
      related to alcohol use later in pregnancy; only subjects' self-efficacy and their
      beliefs about the consequences of drinking during pregnancy predicted their
      subsequent alcohol use. These results are consistent with the notion that greater
      addictive potential lessens the direct impact of psychological factors on
      substance use during pregnancy. Further implications of these findings for
      interventions and other health-related behaviors are also discussed.

PMID- 8876764
TI  - Self-concept changes over time in cognitive-behavioral treatment for smoking
      cessation.
AB  - A smoker self-concept and an abstainer self-concept are individual difference
      variables that have been shown to predict smoking cessation. We examined whether
      these self-concept constructs changed as a function of participating in a clinic
      based smoking cessation program and, specifically, whether these changes occurred
      differentially between posttreatment smokers and abstainers. Subjects completed
      the Smoker Self-concept scale and the Abstainer Self-concept scale at three time
      points: pretreatment, posttreatment, and 3 months' posttreatment. Smoking status
      was assessed and biochemically verified directly after quit day and 3 months'
      posttreatment. Results indicated that abstainers' smoker self-concept decreased
      more precipitously over time compared to smokers'. Abstainers showed consistent
      increases over time in their abstainer self-concept, and smokers showed increases
      followed by decreases to pretreatment levels. Clinical implications are
      discussed.

PMID- 8876765
TI  - Enrollment in a drug-free detention program: the prediction of successful
      behavior change of drug-using inmates.
AB  - Factors predicting the behavior change of drug-using detainees were investigated
      in detainees in two penitentiaries in The Netherlands. Subjects attended either a
      standard program or a Drug-Free Detention Program (DFDP) and were assessed at the
      beginning of detention, at release/transfer, and at 2 years after the end of
      detention. Predictors of postprogram contact with treatment agencies and changes
      in criminal recidivism, substance abuse, and psychosocial functioning were
      investigated using regression analysis. Detainees who started drug use early,
      without previous DFDP detention, and who frequently expressed self-esteem and who
      had many family problems realized meetings with drug treatment agencies more
      often. Those with a legal source of income showed decreases in addiction severity
      and in the number of days in which hard drugs were used. Comparison of the normal
      program and the DFDP showed that only for the normal wing could changes in
      substance use and psychosocial functioning be predicted. Results show the value
      of multiple-outcome criteria in criminal recidivism research and call for more
      studies investigating change processes.

PMID- 8876766
TI  - Seasons and depression: the influence of cigarette smoking.
AB  - The seasonality of depressive illness has been documented since antiquity. A
      review of 611 patients, who were consecutively admitted to the adult inpatient
      psychiatric unit of a mid-Michigan general hospital, examined the influence of
      cigarette smoking and psychiatric diagnosis upon the seasonal variation of
      admissions. Among the smokers, admissions for depressive disorders (n = 151)
      peaked in the springtime (z = 2.1, p < .05) and declined in summer. Admissions
      for the nonsmokers failed to demonstrate a substantial seasonal rhythm.
      Admissions for smokers and nonsmokers in other diagnostic groups did not show any
      seasonal variation. These findings parallel numerous studies regarding the
      influence of seasons upon rates of hospitalization for depressive disorder, and
      completed suicide. Therapeutic implications related to the bidirectional
      relationship between cigarette smoking and depression are discussed.

PMID- 8876767
TI  - The accuracy of self-report of smoking status in pregnant women.
AB  - Little is known about the accuracy of usual-care providers' detection of pregnant
      smokers. This study explored the proportion of pregnant women misclassified as
      nonsmokers by midwives in a public antenatal clinic. A sample of 204 women whom
      midwives classified as nonsmokers were asked to complete a self-administered
      questionnaire and to provide a urine specimen for cotinine analysis. Results
      indicate that midwives failed to detect a significant proportion of smokers. The
      conservative estimate of the proportion of midwife-identified nonsmokers who
      could be reclassified as smokers on the basis of the questionnaire and urinalysis
      procedures was 7.4% (95% CI 3.8-10.9%), the medium estimate was 8.8% (95% CI 4.9
      12.7%) and the worst-case estimate was 15.2% (95% CI 10.3-20.1%). To increase the
      coverage achieved by smoking-cessation programs, antenatal clinics should
      consider incorporating biochemical measurements into routine screening
      procedures. Future studies examining smoking status in pregnancy should detail
      the methods used to classify subjects and document response rates in relation to
      each self-report and biochemical measurement.

PMID- 8876768
TI  - The immune system and major depression.
AB  - This paper reviews research literature on the links between human immune
      functioning and mood disorders. It summarizes the initial steps of this fledgling
      research area since its inception in the late 1970s, and outlines a range of
      studies that are needed to increase our neuroimmunological sophistication. Future
      investigations will require greater specificity in several interrelated realms of
      inquiry: diagnostic, epidemiologic, and physiologic. In particular, this paper
      highlights basic physiological studies needed in both neurophysiology and
      immunology to provide a foundation for meaningful examination of their interface.
      Among the areas that require more specific investigation in both immunologic and
      mood disorders research is that of temporal organization. Just as psychiatric
      researchers have begun to scrutinize temporal cycles of mood, behavior, and
      neurophysiology, so too exploration of immune functioning must take into account
      predictable temporal cycles such as circadian and ultradian rhythms, as they
      shape responses to unanticipated external perturbations. Clarification of the
      temporal dimension will add significantly to our analysis of the links between
      immune functioning and mood disorders. The basic science of psychoneuroimmunology
      continues to mature, bringing new discoveries and revealing hitherto unknown
      mechanisms and interactions. This is a field of study in many ways still on the
      frontier, and explication of the long suspected links between mood disorders and
      immune functioning continues to beckon.

PMID- 8876769
TI  - Neuroimmunologic implications in coronary artery disease.
AB  - In this review, the role of the macrophage in the pathophysiology of coronary
      artery disease (CAD) is examined. The central interaction of macrophage,
      endothelial cell and smooth muscle cell in the context of hyperlipidemia is
      considered. The macrophage appears to be at the beginning of a chain of events
      that starts with elevated low density lipoprotein (LDL). Stress, particularly in
      those with a core hostility, may be associated not only with higher catecholamine
      levels but also with higher serum lipid levels. These lipids will in turn be
      processed to oxidized LDL by macrophage and endothelial cells. Oxidized LDL
      molecules will contribute to atherosclerotic plaquing. A side effect of such
      plaque formation may be a diminished vasodilatory response to the nitric oxide
      (NO) produced by macrophages and endothelium. Indeed, paradoxical
      vasoconstriction occurs in atherosclerosis in response to neurotransmitters such
      as serotonin and acetylcholine, which under normal circumstances cause
      vasodilation. There also is evidence that both macrophages and endothelial cells
      can regulate NO production through a specific mu 3 morphine receptor, an effect
      that can be blocked by naloxone. The clinical effectiveness of morphine and
      nitroglycerin in CAD patients may relate to these mechanisms. More research will
      be needed to elucidate the neuroimmunologic basis for atherosclerosis with
      prospects for better treatment and management in future.

PMID- 8876770
TI  - The neuroimmunology of multiple sclerosis.
AB  - The aim of this clinical review is to highlight recent advances in immunology, as
      well as new information from selected other areas, which have led to a better
      appreciation of the neuroimmunologic mechanisms involved in Multiple sclerosis
      (MS). New data on immunopathology, the cytokine network, and the role of
      oligodendrocytes, lymphocytes, and endothelial cells in this disease, have
      produced novel therapeutic approaches. New information on clinical course and
      neuroimaging disease features, as well as the role of genetic factors and
      infectious agents, have also improved our understanding of the immune basis for
      MS.

PMID- 8876771
TI  - Neuroimmune and neuropsychiatric aspects of chronic fatigue syndrome.

PMID- 8876772
TI  - Psychoneuroimmunology of autoimmune disorders.
AB  - The interactions between the immune system and psychological states are both
      intricate and intriguing. Research at a molecular level has thrown considerable
      light on the previously ill-defined area of psychoneuroimmunology. In this
      report, we explore the psychoneuroimmunology of autoimmune disorders,
      particularly rheumatoid arthritis and lupus erythematosus. Animal models of these
      diseases have provided a particularly useful window on complex
      psychoneuroimmunological interactions. Observations about the effect of stress on
      the onset and course of autoimmune disorders has added to our understanding of
      psychoneuroimmunological interactions. These interactions are bi-directional, as
      reflected in the autoimmune-mediated neuropsychiatric manifestations of systemic
      lupus. Exploring the role of various neurotransmitters and neuromodulators in the
      stress response may have important therapeutic implications for autoimmune
      disorders.

PMID- 8876773
TI  - Psychoneuroimmunology and cancer: historical perspectives and current research.
AB  - The belief that cancer might be related to temperament or distress has been
      emphasized throughout the history of medicine. The field of psychoneuroimmunology
      has its origins in psychosomatic medicine, and has evolved to the investigations
      of complex interactions between the psyche and the nervous, immune, and endocrine
      systems. Such interactions may have implications in both cancer risk and
      survival.

PMID- 8876774
TI  - Molecular mechanisms of microglial activation.
AB  - Microglial cells are brain macrophages which serve specific functions in the
      defense of the central nervous system (CNS) against microorganisms, the removal
      of tissue debris in neurodegenerative diseases or during normal development, and
      in autoimmune inflammatory disorders of the brain. In cultured microglial cells,
      several soluble inflammatory mediators such as cytokines and bacterial products
      like lipopolysaccharide (LPS) were demonstrated to induce a wide range of
      microglial activities, e.g. increased phagocytosis, chemotaxis, secretion of
      cytokines, activation of the respiratory burst and induction of nitric oxide
      synthase. Since heightened microglial activation was shown to play a role in the
      pathogenesis of experimental inflammatory CNS disorders, understanding the
      molecular mechanisms of microglial activation may lead to new treatment
      strategies for neurodegenerative disorders, multiple sclerosis and bacterial or
      viral infections of the nervous system.

PMID- 8876775
TI  - Double-blind, placebo-controlled study of metrifonate, an acetylcholinesterase
      inhibitor, for Alzheimer disease.
AB  - Fifty patients with probable Alzheimer disease (AD) completed a 3-month double
      blind study to compare metrifonate to placebo. We dosed metrifonate to achieve a
      40-60% inhibition of red blood cell acetylcholinesterase activity. The Alzheimer
      Disease Assessment Scale cognitive subscale score (ADAS-C) served as the primary
      outcome measure. At the completion of 3 months of treatment, the metrifonate
      group ADAS-C score differed significantly from the placebo group score by 2.6
      points (p < 0.01). A 0.75-point trend toward improvement occurred during
      treatment in the ADAS cognitive performance of the metrifonate group (p = 0.15),
      and a 1.10-point deterioration in cognitive performance was found in the placebo
      group (p < 0.02). On the Global Improvement Scale (GIS), the two groups differed
      significantly on their changes from baseline to treatment phase (p < 0.02).
      Significant deterioration occurred in GIS scores (p < 0.01) and in Mini Mental
      State Examination (MMSE) scores (p < 0.03) in the placebo-treated group. Adverse
      effects were uncommon and did not require adjustment of the dose of metrifonate
      or discontinuation of treatment. We achieved a mean of 52.3% decrease in red
      blood cell acetylcholinesterase activity. During up to 18 months of subsequent
      open metrifonate treatment of patients, we found a deterioration of 1.68 points
      per year in MMSE performance. These findings support further study of the effects
      of metrifonate on deterioration rate in AD.

PMID- 8876776
TI  - Rationale and design of a multicenter study of selegiline and alpha-tocopherol in
      the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer's
      Disease Cooperative Study.
AB  - This report describes the rationale and design of a clinical trial using
      selegiline (10 mg/day) and alpha-tocopherol (2,000 IU/day) to slow the
      progression of dementia in Alzheimer disease (AD). This study was developed by
      the Alzheimer's Disease Cooperative Study (ADCS), a consortium of clinical
      research centers actively involved in AD research. The major goal of the
      consortium is to design and conduct clinical investigations leading to the
      development of treatments for AD. This study uses a randomized double-blind,
      placebo-controlled, 2 x 2 factorial, parallel group design to test two drugs for
      the treatment of AD. The primary outcome of the study is the time to reach any
      one of the following four endpoints: death, institutionalization, loss of two of
      three basic activities of daily living, and progression of Clinical Dementia
      Rating (CDR) stage from 2 to 3. Patients with moderately severe disease (CDR = 2)
      were enrolled and evaluated 10 times over a period of 2 years to determine if
      these agents reduce the time to reach any endpoint. A database from the
      Consortium to Establish a Registry for Alzheimer's Disease indicated adequate
      power analyses to observe a treatment effect on this clinically meaningful
      outcome measure. Recruitment and baseline characteristics of the population are
      provided. The rationale for the choice of a factorial design, the use of a novel,
      clinically meaningful endpoint, and the selection of a cohort of patients with AD
      of moderate severity are discussed.

PMID- 8876777
TI  - Positron emission tomography metabolic data corrected for cortical atrophy using
      magnetic resonance imaging.
AB  - The correct interpretation of clinical positron emission tomography (PET) data
      depends largely on the physical limits of the PET scanner. The partial volume
      effect (PVE) is related to the size of the studied object compared to the spatial
      resolution. It represents one of the most important limiting factors in
      quantitative data analysis. This effect is increased in the case of atrophy, as
      in patients with Alzheimer disease (AD), and it influences measurement of the
      metabolic reduction generally seen in cerebral degeneration. In this case,
      interpretation can be biased, because cortical activity will be underestimated
      due to the atrophy. In general, anatomical images of AD patients have shown
      diffuse atrophy, while PET studies have found widespread hypometabolism affecting
      the parietal and temporal lobes. Although hypometabolic areas usually correspond
      to atrophic regions, they also occur without such changes. Thus, the aim is to
      differentiate authentic hypometabolism (decrease of glucose consumption per unit
      volume of gray matter) from that due to PVE from atrophy (cell loss).
      Consequently, we are using a method for three-dimensional (3D) correction of
      human PET data with 3D magnetic resonance imaging (MRI). We measured atrophy and
      metabolism by using both T1-weighted MR images and high and medium resolution PET
      scans. We injected 12 patients and controls with [18F]fluorodeoxyglucose for
      glucose consumption measurements. Atrophy was estimated in the following way. We
      isolated the cerebral structures, using a segmentation technique on the MRI
      scans, into gray matter (GM), white matter, and cerebrospinal fluid. We
      superimposed the PET images onto the MR images to obtain anatomo-functional
      correlations. We degraded the segmented MR images to the resolution of the PET
      images by a convolution process to create a PET image correction map. We
      corrected the metabolic PET data for the PVE. We studied the cerebral metabolic
      rate of glucose in the GM where metabolic variation is the most relevant to AD.
      By dealing with problems relating to the sensitivity to the segmentation and to
      the PET-MRI coregistration, computation of MRI convolution processes provided the
      degree of PVE on a pixel-by-pixel basis, allowing correction of hypometabolisms
      contained in GM PET values. Global cortical metabolism increased after correction
      for PVE by, on average, 29 and 24% for tomographs acquired with medium (TTV03
      LETI) and high (ECAT 953B CTI/Siemens) resolution, respectively, whereas the
      cortical metabolism increased by 75 and 65% for the respective tomographs in AD
      patients. The difference of metabolism between scans after correction for PVE was
      less than before correction, decreasing from 31 to 17%. This difference was most
      marked in the frontal and temporal lobes. Fusion imaging allowed correction for
      PVE in metabolic data using 3D MRI and determination of whether a change in the
      apparent radiotracer concentration in PET data reflected an alteration in GM
      volume, a change in radiotracer concentration per unit volume of GM, or both.

PMID- 8876778
TI  - Content of brain aluminum is not elevated in Alzheimer disease.
AB  - Several studies have reported that the bulk aluminum (Al) concentration is
      increased in the brain in Alzheimer disease (AD), while other studies have failed
      to demonstrate an increase. Most of these investigations have had one or more
      methodological deficiencies, including lack of adequate neuropathological
      assessment; failure to age-match the control samples; small sample sizes, lacking
      statistical power; and geographical heterogeneity in the AD and control
      populations. The present population-based study of 92 clinically and
      histopathologically diagnosed AD patients and normal elderly nursing home
      residents was designed to avoid these potential biases. When a subsample of AD
      cases with the most severe brain pathology was compared with controls having no
      or minimal pathology, no statistically significant differences were found in the
      bulk aluminum concentration measured by graphite furnace atomic absorption
      spectrometry in frontal cortex (1.8 +/- 0.7 vs. 1.7 +/- 0.7 micrograms/g dry wt),
      temporal cortex (1.4 +/- 0.3 vs. 1.5 +/- 0.5 micrograms/g dry wt), liver (2.0 +/-
      1.3 vs. 2.0 +/- 1.2 micrograms/g dry wt), or head of femur (2.4 +/- 1.6 vs. 2.2
      +/- 1.0 micrograms/g ash wt). Within the whole series of 92 cases, there was no
      difference in the bulk aluminum concentration of the frontal cortex between
      individuals diagnosed as definite, probable, and possible cases of AD using the
      CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. The
      density of senile plaques and neurofibrillary tangles in frontal and temporal
      cortex showed no correlation with the bulk aluminum concentration. Logistic
      regression analyses, which controlled for age and sex, did not influence outcome
      for any of the comparisons. The data show conclusively that in AD, bulk aluminum
      concentration is not increased in two cortical brain regions that are selectively
      vulnerable to the neuropathological changes associated with this disorder.

PMID- 8876779
TI  - Fisher symposium: strategies for the prevention of Alzheimer disease--overview of
      research planning meeting III.
AB  - Even though the prospect for preventing Alzheimer disease seems remote now, a
      plan must be developed to reach this goal in order to avoid a fiscal crisis in
      the health care system. The goals of delaying Alzheimer disease and eventually
      preventing it will become possible as more is learned about the brain mechanisms
      and risk factors involved. In response to a 1994 Congressional report, the
      National Institute on Aging in cooperation with the Zachary and Elizabeth M.
      Fisher Medical Foundation sponsored a workshop to address potential strategies
      for the prevention of Alzheimer disease. The workshop helped to identify the
      necessary resources and the types of technical problems involved in developing
      methods to prevent Alzheimer disease. This volume presents the position papers
      which served as the springboard for the discussions at the workshop, out of which
      developed a number of specific recommendations including new epidemiological
      studies for well defined population groups, identification of high risk
      populations for treatment and prevention studies, and coupling of new questions
      and add-on investigations to in-progress studies.

PMID- 8876780
TI  - Potential prevention strategies for Alzheimer disease.
AB  - Primary prevention trials for Alzheimer disease (AD) should be considered because
      of the substantial cost of caring for AD patients. Current clues to possible
      treatments include the potential use of antioxidants, estrogens, anti
      inflammatory drugs, drugs designed to alter apolipoprotein E4 status, and
      compounds altering amyloid metabolism. Because of the expense of primary
      prevention trials, resources should be devoted to developing epidemiological
      clues for environmental loss in vivo and searching for additional epidemiological
      clues for environmental factors that may protect individuals from AD. A primary
      prevention trial would involve the recruitment of 4,000-5,000 subjects followed
      for 3-5 years at a cost of approximately $20 million. Alternatively, a primary
      prevention trial could be performed as an "add on" study to an existing clinical
      trial of a compound of interest currently being tested in an elderly population
      at substantially less cost.

PMID- 8876781
TI  - Prevention of Alzheimer disease: a perspective based on successes in the
      prevention of other chronic diseases.
AB  - Alzheimer disease, like other common chronic diseases, likely has genetic and
      environmental risk factors. Prevention of arteriosclerotic vascular disease has
      occurred based on efforts to reduce risk factors demonstrated in epidemiologic
      and more basic science research. At present, there are no known risk factors for
      Alzheimer disease which could form the basis of a preventive strategy. To make
      progress in the prevention of Alzheimer disease, new findings from epidemiology
      and basic science will be needed. The current state of the art of epidemiologic
      studies of dementia is well enough developed to test credible hypotheses. The
      availability of reliable biomarkers along with cooperative efforts between
      molecular biologists and clinical epidemiologists should allow us to pursue
      promising fields in clinical research.

PMID- 8876782
TI  - Potential prevention of Alzheimer disease and dementia.
AB  - The prevention of dementia is of critical importance. The increasing population
      of high-risk older individuals will result in an increasing prevalence of
      dementia. Primary prevention of dementia and Alzheimer disease can take either a
      public health or high-risk preventive medicine approach. At the present time,
      there is little evidence to support a specific primary public health approach
      such as a specific nutrient. The possible association of vascular disease with
      dementia may offer the best preventive high-risk approach. The identification of
      individuals with clinical and subclinical vascular disease is possible. There is
      a very high prevalence of subclinical cerebral infarction in older individuals.
      Specific treatments can prevent clinical disease such as stroke and coronary
      heart disease. Whether therapies will prevent some dementia can be determined.

PMID- 8876783
TI  - Approaches to the prevention of Alzheimer disease.
AB  - Once preventive measures for Alzheimer disease are identified, there will be
      great pressure to implement programs to reduce the impact of the disease. The
      development of effective programs will require detailed information on the
      characteristics of the disease, which can be collected now, and on the
      characteristics of the intervention which should be collected during the
      intervention trial. Without this information, the implementation of an effective
      prevention program would be needlessly delayed.

PMID- 8876784
TI  - Outcome variables in presymptomatic individuals at higher risk of developing
      Alzheimer disease.
AB  - The treatment of individuals at risk of Alzheimer disease is feasible in well
      designed, placebo-controlled, double-blind studies. The favored design would be
      life survival for cognitive impairment, alterations in instrumental ADL, and
      selected biological variables.

PMID- 8876785
TI  - The use of genetic information in large-scale clinical trials: applications to
      Alzheimer research.
AB  - A great deal of secondary, or covariable, information is often collected during
      the course of large-scale clinical trials. This information typically includes
      demographic and anthropometric data but often also includes more elaborate
      laboratory-based measures that might be used to screen for adverse reactions to
      the preventive agent or treatment being tested. This information can be and often
      is used to identify individuals or, more likely, subgroups of individuals who
      appear to respond better (or worse) to the compound of relevance. Such
      heterogeneity in response is to be expected, since the basic biological
      constitution of individuals differs widely and since it is well known from simple
      pharmacokinetic assays that such differences can affect drug responses. Since
      genes influence the biological constitution of individuals, it is easy to argue
      that genetic differences between individuals could explain differential
      responsiveness to certain drugs, as pharmacogeneticists have suggested for years.
      In this article, it is argued that by collecting relevant genetic data on
      participants in large-scale clinical trials as though these data merely provided
      additional covariables, one might not only be in a position to identify
      responders and nonresponders to the compound being tested but could also be in a
      position to address fundamental questions about the nature and pathogenesis of
      the disease for which the compound was designed. Although we exemplify this
      simple argument by referring to antihypertensive compounds and research, this
      reference is made merely for reasons of convenience, since there are numerous
      compounds designed expressly for the prevention and treatment of hypertension,
      but rather few for Alzheimer disease. It is hoped that by adopting some of the
      guidelines and principles outlined herein, better and more appropriate compounds
      for the prevention and treatment of Alzheimer disease will be tested and
      ultimately made available to the patients for whom they work best.

PMID- 8876786
TI  - Statistical issues in prevention and therapeutic trials of Alzheimer disease.
AB  - Relatively little attention has been given to the proper design and statistical
      analysis of prevention and therapeutic trials of Alzheimer disease (AD). A number
      of important methodological issues arise in studies of AD that do not typically
      arise in studies of other chronic diseases. These issues include: the definition
      of the primary study endpoint that is simple to measure and easy to interpret;
      proper design of trials that take into account that the patient population is
      very old; and the proper statistical analysis that addresses the high drop out
      rate and the multiple ways of measuring disease severity. Addressing these issues
      will speed the progress of the evaluation of promising compounds to prevent and
      treat AD.

PMID- 8876787
TI  - Observations and suggestions on antidementia drug development.
AB  - Recent advances in the theoretical neurosciences have suggested a number of novel
      strategies that might be applied to prevent and/or retard the progression of
      Alzheimer disease. Whether or not these interventions will succeed cannot be
      determined on theoretical grounds, however; the value of each new stratagem must
      be evaluated in patients with Alzheimer disease. How best to conduct clinical
      studies of disease-modifying treatments remains a controversial subject. The
      author reviews and compares two clinical trial designs that may prove useful in
      assessing whether or not a putative treatment actually modifies the course of
      dementia.

PMID- 8876788
TI  - Issues in accelerating the pace of development for neuroprotective agents.
AB  - Accelerating the pace of development for neuroprotective agents requires a number
      of advances in the therapeutics of Alzheimer disease. Identification of patients
      who are presymptomatic, by discovering early markers of Alzheimer disease will be
      essential. Clinical trials methodology must be devised to accommodate atypical
      outcome measures, prolonged trials, and large sample sizes without posing serious
      ethical considerations regarding placebo administration. Finally, regulatory
      issues that discourage development of drugs that will be in complicated,
      expensive and lengthy clinical trials need to be addressed. This paper reviews
      these issues, and offers some suggestions.

PMID- 8876789
TI  - Development of a national prospective study of Alzheimer disease.
AB  - The purpose of this commentary is briefly to review the genetic, social,
      demographic, and environmental factors associated with Alzheimer disease with the
      specific purpose of planning an intervention to prevent or possibly delay the
      onset of disease. Complex disorders such as Alzheimer disease are the result of
      one or more genes and other contributing risk factors. For example,
      apolipoprotein E (APOE) genotypes can indicate a degree of susceptibility, but
      the gene is neither "necessary nor sufficient" to cause the disease. Thus, many
      potential risk factors remain to be identified. The association between Alzheimer
      disease and APOE also varies with age, genetic background, and ethnic group.
      While the use of APOE genotyping has provided a method to identify individuals at
      greatest risk of Alzheimer disease, how other factors modify the degrees of the
      APOE-related risk needs to be further investigated. Moreover, the effect of APOE
      on disease course and various noncognitive manifestations warrant scrutiny.
      Because risk prediction is not straightforward, practical issues related to
      developing a national strategy to prevent or delay the onset of Alzheimer disease
      require careful consideration, planning, and an organized interdisciplinary
      effort.

PMID- 8876790
TI  - Is a randomized trial of antioxidants in the primary prevention of Alzheimer
      disease warranted?
AB  - Alzheimer disease is a common condition that severely affects both persons with
      the illness and their families. Prevention of Alzheimer disease is an urgent
      priority, but study of potentially modifiable risk factors for the illness is at
      an early stage. Laboratory studies suggest that oxidative mechanisms may be
      involved in the pathogenesis of Alzheimer disease and raise the possibility that
      antioxidant nutrients could be used in disease prevention. Observational studies
      suggest that antioxidant nutrients may have protective effects against a number
      of other common chronic diseases, including cardiovascular disease and cancer.
      Because the protective effects, if any, of antioxidant nutrients are likely to be
      small to moderate in magnitude, large-scale randomized trials of primary
      prevention will likely be necessary to resolve this issue, and a major question
      is how quickly to progress to expensive and time consuming trials needed to
      provide more definitive evidence. This is a difficult question, but the severity
      of the disease, the current absence of preventive strategies and the likelihood
      that observational studies alone will not provide clear resolution of the issue
      all suggest that it may be prudent to strongly consider such trials in the near
      future.

PMID- 8876791
TI  - Screening for asbestos-induced diseases in Finland.
AB  - Screening for asbestos-induced diseases in Finland was carried out in 1990-1992
      as a part of the Asbestos Program of the Finnish Institute of Occupational
      Health. The aim of the present study was to find the workers who had developed an
      asbestos-induced disease in certain occupations. Examination of active or retired
      workers included a personal interview on work history and asbestos exposure, and
      a chest X-ray. The target group for the screening comprised workers under 70
      years of age who had worked at least for 10 years in construction, 1 year in a
      shipyard or in the manufacture of asbestos products. A preliminary questionnaire
      was sent to 54,409 workers, 18,943 of whom finally participated in the screening
      examination. The mean age of the workers was 53 years; 95% were employed in
      construction, 2% in shipyards, and 3% in the asbestos industry. The criteria for
      a positive screening result were (1) a radiographic finding clearly indicating
      lung fibrosis (at least ILO category 1/1), (2) a radiographic finding indicating
      mild lung fibrosis (ILO category 1/0) with unilateral or bilateral pleural
      plaques, (3) marked abnormalities of the visceral pleura (marked adhesions with
      or without pleural thickening), or (4) bilateral pleural plaques. The positive
      cases totalled 4,133 (22%) and were sent for further investigation. In addition
      to the screening, information on the presence of asbestos in the work
      environment, prevention of asbestos exposure, as well as on the health effects of
      asbestos exposure and smoking were given to the participating workers. The
      screening acted as a preliminary survey to prompt further national follow-up of
      asbestos-induced diseases among the workers who have been exposed to asbestos.
      This article presents the material, methods, and overall results of the
      screening.

PMID- 8876792
TI  - Chrysotile asbestos is the main cause of pleural mesothelioma.
AB  - In contrast to amphibole forms of asbestos, chrysotile asbestos is often claimed
      to be only a minor cause of malignant pleural mesothelioma, a highly fatal cancer
      of the lining of the thoracic cavity. In this article we examine the evidence
      from animal and human studies that relates to this issue. Reported data do not
      support widely quoted views regarding the relative inertness of chrysotile fibers
      in mesothelioma causation. In fact, examination of all pertinent studies makes it
      clear that chrysotile asbestos is similar in potency to amphibole asbestos. Since
      asbestos is the major cause of mesothelioma, and chrysotile constitutes 95% of
      all asbestos use world wide, it can be concluded that chrysotile asbestos is the
      main cause of pleural mesothelioma in humans.

PMID- 8876793
TI  - Colorectal cancer in asbestos cement workers in Denmark.
AB  - Recent data on the risk of colorectal cancer following exposure to chrysotile are
      conflicting. We report on colorectal cancer morbidity in a large cohort of
      asbestos cement workers from Denmark mainly exposed to chrysotile. The total
      cohort had an SIR of 1.23 (95% CI 1.01-1.48). With a latency period of 15 years,
      men employed in the early (1928-1950) production period had an SIR of 1.47 (95%
      CI 1.05-2.01). With the observation of excess risks of colorectal cancer
      morbidity among chrysotile exposed asbestos cement workers in both Sweden and
      Denmark the question on the role of chrysotile in the etiology of colorectal
      cancer remains open.

PMID- 8876794
TI  - Respiratory health services reported by U.S. mining facilities in the National
      Occupational Health Survey of Mining (1984-1989).
AB  - This report describes the involvement of mine management personnel at U.S. mines
      in providing environmental and medical services related to respiratory health.
      The data were obtained by means of a questionnaire that was administered to mine
      management personnel at 491 mines and mills during May 1984 to August 1989. The
      data indicate that 62% of U.S. miners worked at facilities that provided at least
      a portion of workers with chest X-rays, and 41% worked at facilities that
      provided at least a portion of workers with pulmonary function tests. Eighty-five
      percent of miners worked at facilities in which the company required a medical
      examination of all new employees; the majority were required by company policy to
      have a medical examination before returning to work after an illness. However,
      only 2% of miners were required by company policy to have an exit medical
      examination when their employment ended. This report underscores the need for
      respiratory health to remain a primary concern of all persons who provide
      occupational health services to miners.

PMID- 8876795
TI  - Decrease in selenium status in relation to coal dust exposure.
AB  - Selenium (Se) plasma levels were studied in 222 coal miners to assess whether
      selenium is decreased in relation to coal dust exposure, taking age, alcohol, and
      tobacco consumption into account. Selenium levels decreased significantly with
      age and current tobacco consumption, among miners aged 34-50. Long-term and
      current exposure to coal dust were studied. The lowest Se values were observed
      for those with both long-term and current exposure (60.2 ng/ml), the highest for
      those never or slightly exposed (64.1 ng/ml); those with long-term exposure not
      currently exposed fell in an intermediate position (61.3 ng/ml). No relation was
      observed with alcohol consumption. The association of coal dust with low selenium
      remained significant after adjustment for age and smoking.

PMID- 8876796
TI  - Case-control study of exposure to carbon black in the occupational setting and
      risk of lung cancer.
AB  - Although it has been hypothesized that carbon black exposure may carry an excess
      risk of lung cancer, evidence to date is insufficient to assess the hypothesis
      properly. The relationship between workplace exposure to carbon black and lung
      cancer risk was examined in a population-based case-control study carried out in
      Montreal, Canada. Detailed job histories were elicited from 857 incident cases
      with histologically confirmed lung cancer as well as from 1,360 cancer controls
      and 533 population controls. Job histories were evaluated by a team of hygienists
      and chemists for evidence of exposure to a host of occupational substances,
      including carbon black. Logistic regression analyses adjusting for smoking and
      other nonoccupational and occupational potential confounders suggested no
      significant increase in risk with relatively low exposure to carbon black. Some
      increase in risk for all lung cancers was apparent with relatively high exposure
      using cancer controls (OR = 2.17; 95% CI = 0.95-4.91) and population controls (OR
      = 1.52; 95% CI = 0.58-3.97). Individuals with relatively high exposure had a
      significantly greater risk of oat-cell carcinoma using either control series (OR
      = 5.05; 95% CI = 1.72-14.87 using cancer controls and OR = 4.82; 95% CI = 1.36
      17.02 using population controls). These results provide some evidence for an
      association between exposure to carbon black and lung cancer.

PMID- 8876797
TI  - Respiratory symptoms and pulmonary function in mill workers exposed to wood dust.
AB  - This study surveyed wood dust exposure levels and pulmonary hazards among wood
      mill workers. Dust concentrations as measured by six-stage cascade impactors were
      high in work areas of grinding and screening. Total dust concentrations for these
      dusty activities ranged from 4.4 to 22.4 mg/m3, and the respirable proportions
      were between 2.4% and 50.2%. The dust level in the sawing work was 2.9 mg/m3.
      Although symptoms of cough and phlegm were higher in smoking workers than in
      nonsmoking workers, the prevalence of respiratory symptoms in the exposed workers
      was not significantly higher than in the controls. However, the incidence of
      symptoms such as chronic phlegm and chronic bronchitis in the nonsmoking high
      exposure workers was significantly higher than in nonsmoking controls. The mean
      values of MMF, PEFR, and FEF25% were significantly lower in the exposed workers
      than in controls for both smokers and nonsmokers. The pulmonary function
      deficits, with the exception of FEV1.0/FVC, also showed a significant trend with
      increasing levels of wood dusts exposure classified by job titles for both
      smokers and nonsmokers. After adjustment for age, sex, height, and smoking
      status, all parameters of pulmonary function were significantly lower in exposed
      workers than in controls and showed a declining trend with increasing exposure
      levels classified by job titles. These results indicate that high level of wood
      dust exposure in the wood mill industries may lead to pulmonary hazards.
      Engineering control and industrial hygiene are mandatory for dusty activities.

PMID- 8876798
TI  - Cancer incidence among alachlor manufacturing workers.
AB  - A historical cohort study was conducted to evaluate cancer incidence among
      chemical workers with occupational and environmental exposure to alachlor, the
      active ingredient in a family of pre-emergent acetanilide herbicides. The study
      followed 943 workers with at least 1 year of cumulative employment at the
      Monsanto plant in Muscatine, Iowa, from startup of the alachlor manufacturing
      process in March 1968 through December 1990. Approximately 96% of all workers
      were successfully traced to determine their last known residence and cancer
      status. Eighteen workers were diagnosed with cancer during the follow-up period,
      based on pathology information from the statewide cancer registry maintained by
      the State Health Registry of Iowa. The standardized incidence ratio for all
      cancers was 1.5 (95% CI 0.9-2.4) for all workers exposed to alachlor, which was
      due primarily to elevated rates for colorectal cancer and chronic myeloid
      leukemia. Workers with 5 or more years in estimated high alachlor exposure jobs
      had elevated rates of colorectal cancer (3 cases, SIR = 5.2, 95% CI 1.1-15.1).
      Interpretation of the study results is limited by the small size of the study
      population, minimal length of follow-up, and current information concerning
      alachlor metabolism in primates and humans. Nonetheless, the findings suggest the
      need for continued evaluation of this and other alachlor-exposed cohorts.

PMID- 8876799
TI  - Male and female employment in the textile industry in relation to miscarriage and
      preterm delivery.
AB  - To address potential reproductive hazards in textile manufacturing, we conducted
      a community-based case-control study in central North Carolina. Miscarriage cases
      were identified from medical records (280 interviewed cases): preterm delivery
      cases and term, normal birth weight controls (454 and 605, respectively) were
      identified from area hospitals. Exposures were based on job title, an interview
      concerning textile-related exposures, expert imputation of exposure based on job
      titles and interviews, and self-reported exposures by women. Relative to women
      and men working in nonhazardous occupations, workers in the textile industry were
      not at increased risk of miscarriage or preterm delivery, with the possible
      exception of preterm delivery among women and men employed in sectors other than
      knitting and yarn mills and men employed in yarn mills. Inferred exposures to
      specific agents were also not associated with adverse pregnancy outcome. Subject
      to uncertainty in exposure assessment and nonresponse, these data indicate an
      absence of adverse effects of the textile workplace environment on these
      pregnancy outcomes.

PMID- 8876800
TI  - Genotoxic effects in workers exposed to low levels of benzene from gasoline.
AB  - To study genotoxic effects of exposure to low levels of benzene, single-strand
      breaks (SSB) in DNA of leukocytes and urinary levels of the oxidative DNA adduct
      8-hydroxydeoxyguanosine (8OHdG) were determined in 33 men occupationally exposed
      to benzene from gasoline and in 33 controls. The average exposure to benzene over
      a shift was determined by personal air sampling in the breathing zone. The 8-hr
      time-weighted average exposure to benzene was 0.13 ppm (mean value, range 0.003
      0.6 ppm). Exposed workers had a significant increase of SSB (p = 0.04) over the
      shift compared with controls. Storage time of the samples seemed to affect the
      results. An analysis of samples with the same storage time showed a
      nonsignificant increase among the workers compared with controls. Urinary 8OHdG
      increased over the shift among the exposed workers but not among the controls.
      The highest values among the exposed workers were seen in late evening, with a
      slight decrease the next morning. Multiple linear analysis adjusting for smoking
      habits showed a significant association between the exposure level of benzene
      during the shift and the increase of 8OHdG in the urine over the shift among
      exposed workers (p = 0.02). These findings indicate a genotoxic effect in humans
      of benzene at relatively low exposure levels, that is, about 0.1 ppm (0.3 mg/m3).

PMID- 8876801
TI  - Fatalities in the construction industry in the United States, 1992 and 1993.
AB  - To improve the estimates of occupational fatality rates for persons employed in
      the construction industry, several sources of data on the number of fatalities
      (the numerator) and the number of persons engaged in construction work (the
      denominator) were examined. Based on this examination, the Census of Fatal
      Occupational Injuries (CFOI), complied by the Bureau of Labor Statistics (BLS),
      was used to obtain numerators and the Current Population Survey, conducted by the
      Bureau of the census for the BLS, was used to obtain denominators. Adjustments
      were made in the numerator to include only occupations that were included in the
      denominator. Occupations were divided into two groups-those in the construction
      trades and those in other occupations within construction (e.g., clerical,
      sales). The analysis found fatality rates of 14.2 and 13.3 per 100,000 person
      years, respectively, for 1992 and 1993, with wide variation in rates among the
      different trades. There were also major differences among the trades in the types
      of fatal injuries. Self-employed workers had much lower death rates overall than
      wage workers, but this is largely due to much lower proportions of high hazard
      trades among the self-employed. There have been wide variations in the
      occupational fatality rates reported for construction workers each year due to
      the differing methods of estimating the number of fatalities by the different
      data sources. This study provides a baseline of fatality rates using the best
      available current data. It compares the results from these data sources with
      those from other sources that have been used and discusses some of the problems
      inherent in the data from other sources. This study provides a significantly
      improved protocol for the calculation of fatality rates against which later rates
      can be compared consistently. Nevertheless, many deficiencies in the data sources
      used are identified. There remains ample room for continued improvement.

PMID- 8876803
TI  - Chlorinated hydrocarbon solvents and biliary-pancreatic cancer: report of three
      cases.
AB  - This paper describes three men, aged 45 years or younger, who developed
      cholangio, ampullary, and pancreatic cancer after prolonged heavy exposure to
      trichlorinated hydrocarbon solvents. Two of these patients had exposure to other
      potential carcinogens, and one had a strong family history of cancer. The
      association between chlorinated hydrocarbons and biliary-pancreatic cancer has
      also been suggested by other reports in the recent literature. Exposure to
      trichlorinated hydrocarbon solvents is a risk factor for the development of
      biliary and pancreatic cancer.

PMID- 8876802
TI  - Risk factors for coronary heart disease among firefighters in Cincinnati.
AB  - Since 1984, coronary heart disease (CHD) risk factors have been prospectively
      assessed among Cincinnati firefighters free of CHD at study entry. In total, 806
      firemen with a mean age of 37 years at entry have been followed for 6.4 years on
      average, contributing 5,173 person-years. CHD risk factors were measured every 1
      4 years and included weight, blood pressure, cigarette use, fasting glucose, and
      lipid profile. When, in aggregate, these CHD risk factors were found to be in a
      high risk range, suggestions were made serially to reduce CHD risk. A composite
      high CHD risk factor score led to an exercise electrocardiogram (ECG) with
      thallium scan, which was repeated every 1-4 years. Myocardial infarction (MI)
      occurred in 7 men, with 1.35 MIs/1,000 man-years; 15 others developed CHD, with
      4.25 MI + CHD/1,000 man-years. The firefighters' MI event rate (1.35 MIs/1,000
      man-years) was lower (but not significantly, p > 0.1) than that for employed 30-
      to 39-year-old men free of CHD at entry (2.07/1,000 man years), who had an
      average follow-up of 5.4 years in the NHANES I study. At study entry, the 22 men
      who later developed CHD (vs. the 784 who did not develop CHD) were older (p =
      .0001), smoked more (p = .0001), and were more likely to have first degree
      relatives with CHD before age 60 (p = .017). After covariance adjusting for age,
      race, and Quetelet index, men with CHD (vs. those CHD free) had higher systolic
      and diastolic blood pressures (p = .0001, .0001), higher LDL cholesterol (p =
      .04), higher total cholesterol (p = .014), and higher triglycerides (p = .03). By
      Poisson regression, significant independent predictors of CHD events were age (p
      = .0007), cigarette smoking (p = .001), diastolic blood pressure (p = .056), and
      family history of CHD at age < or = 60 (p = .048). Men who later developed CHD
      and those without CHD did not differ by history of smoke inhalation (p > 0.3).
      The calculated ratio of savings to cost attributable to the program per year was
      5.9/1 ($258,500/$43,600). In the current study, firefighting as an occupation was
      not associated with increased CHD event rates. CHD events that did develop were,
      for the most part, associated with modifiable CHD risk factors.

PMID- 8876804
TI  - Exposures and health effects: an evaluation of workers at a sodium azide
      production plant.
AB  - Sodium azide is the principal gas-generating agent used to inflate automobile
      supplemental restraint systems, more commonly called airbags. Although sodium
      azide is known to affect the cardiovascular system by causing peripheral
      vasodilation, there is no published literature describing occupational exposures
      to sodium azide in the rapidly growing automobile airbag industry. In 1994-1995,
      the National Institute for Occupational Safety and Health (NIOSH) conducted a
      cross-sectional study of health complaints reported by sodium azide production
      workers at the only continuous sodium azide production facility in the United
      States. The NIOSH evaluation consisted of a plant industrial hygiene survey, a
      symptom questionnaire, ambulatory blood pressure monitoring, and blood azide
      analysis. Personal breathing zone air monitoring revealed exposures to sodium
      azide and hydrazoic acid (a reactant product) at levels greater than the NIOSH
      Recommended Exposure Limits (RELs). In some cases, exposures exceeded the REL
      despite the use of air-supplied respirators. The questionnaire revealed that most
      workers reported headache (10 of 11 [91%]), episodes of low blood pressure (9 of
      11 [82%]), and palpitations (8 of 11 [73%]) occurring in the production areas
      within the 6 months preceding the study. Mild headache (4 of 11 [36%]) was the
      only symptom reported during our 24-hr medical survey. Ambulatory blood pressure
      monitoring revealed one asymptomatic employee with a drop in blood pressure
      (defined as a drop in systolic [at least 20 mm Hg] and diastolic [at least 10 mm
      Hg] blood pressure) during a period of exposure to sodium azide at a level five
      times the NIOSH REL. Improvements in plant engineering controls, increased
      attention to employee hygiene practices, and a more comprehensive respiratory
      protection program were recommendations made by NIOSH to reduce exposures at the
      plant. All facilities handling sodium azide should be aware of the potential
      toxicity of sodium azide and hydrazoic acid.

PMID- 8876805
TI  - Lead poisoning in telephone cable strippers: a new setting for an old problem.
AB  - Lead poisoning among workers processing lead sheathed telephone cable was
      identified at five worksites. High blood lead levels (BLLs) were identified
      during the medical evaluation of symptomatic workers following employer mandated
      air monitoring and through employer mandated blood lead levels. Once high BLLs
      were identified, governmental agencies became involved at every site, either as a
      result of worker complaints to OSHA or as a registry reporting mechanism.
      Workplace evaluation revealed significant overexposure to lead, particularly
      among workers mechanically stripping the lead sheaths. After intervention by a
      government agency, four of the workplaces chose to stop lead cable processing.
      Because the ongoing replacement of lead sheathed telephone cable with fiber
      optics may be continuing in many areas of the country, there is concern that the
      clusters we have identified represents a widespread and little recognized setting
      for lead overexposure. Recommendations for preventing overexposure to lead in
      this setting are given.

PMID- 8876806
TI  - Prevalence of abnormal median nerve conduction in applicants for industrial jobs.
AB  - There has been much debate regarding the work relatedness of carpal tunnel
      syndrome (CTS) and whether workers diagnosed with CTS had pre-existing disease at
      the time they were hired. To elucidate the latter issue, we examined the
      prevalence of abnormal median nerve conduction within the carpal tunnel in
      applicants for industrial jobs. Nerve conduction studies (NCS) were performed on
      both hands of 1,021 applicants following a conditional offer of employment. Each
      applicant completed a self-administered symptom survey specific to the upper
      extremity. Applicants had worked previously for an average of 4.4 (range 0-33)
      years and had a mean age of 30.1 (S.D. 8.9) years. Nerve conduction studies were
      performed in a private medical clinic. Sensory palmar latencies were determined
      over an 8 cm segment for the median and ulnar nerves. The difference between the
      median and ulnar sensory latencies was the primary electrophysiologic measurement
      used to determine median neuropathy. Using a very conservative criterion for
      abnormal median nerve conduction, 17.5% of the applicants were classified with
      neuropathy in at least one hand. Despite the relatively high prevalence of median
      neuropathy, relatively few (10%) with positive NCS acknowledged symptoms
      associated with CTS. Males had a higher percentage of median neuropathy than did
      females. We conclude that a large percentage of industrial workers have objective
      evidence of abnormal median nerve conduction within the carpal tunnel when hired.
      The high prevalence of abnormal median nerve conduction without corresponding
      symptoms may suggest a subclinical entity associated with CTS.

PMID- 8876807
TI  - Self-reported carpal tunnel syndrome: predictors of work disability from the
      National Health Interview Survey Occupational Health Supplement.
AB  - The objective of this study was to identify risk factors for work disability
      among persons with carpal tunnel syndrome (CTS). The study was designed to
      analyze data from the Occupational Health Supplement of the National Health
      Interview Survey, a nationwide, population-based survey. Subjects included 544
      survey respondents with self-report of CTS and 32,688 survey respondents without
      CTS, all aged 18-64 years, and with a history of labor force participation.
      Measurements were as follows: Dependent variables were work disability, defined
      either as cessation of employment without attribution of cause or, alternatively,
      as cessation of employment or job change specifically attributed to CTS by the
      survey respondent. Independent variables were ergonomic risk of work disability,
      defined by minutes of workplace repetitive hand and wrist bending for the most
      recent job held. This measure was derived from responses categorized by an
      occupation and industry matrix independent of CTS status. Socio-demographic and
      health status risk factors for work disability were based on the respondent
      report. The main results were as follows: Among 544 persons with CTS, 58 (11%, CI
      8-13%) reported work disability specifically attributed to CTS, representing an
      estimated national prevalence of 240,578 persons with this limitation. Workplace
      ergonomic risk, measured as repetitive hand or wrist bending in the occupation
      and industry of last employment, was a significant factor predictive of CTS
      attributed work disability (per 120 min of daily exposure, OR 1.7, CI 1.1-2.6),
      even after taking into account socio-demographic factors and health status. The
      conclusions were that work disability among persons with CTS is common. For those
      with CTS, working conditions characterized by repetitive bending of the hand or
      wrist may increase the risk of work disability associated with this condition.

PMID- 8876808
TI  - The asbestos TLV: early evidence of inadequacy.

PMID- 8876810
TI  - HLA class II alleles in Ainu living in Hidaka District, Hokkaido, northern Japan.
AB  - The Ainu people are considered to be the descendants of preagricultural native
      populations of northern Japan, while the majority of the population of
      contemporary Japan (Wajin) is descended mainly from postneolithic migrants.
      Polymorphisms of the HLA-DRB1, DRB3, and DQB1 alleles were investigated in DNA
      samples of 50 Ainu living in Hidaka district, Hokkaido. Unique features of the
      Ainu in this study were high incidences of DRB1*1401, DRB1*1406, and a newly
      described allele, DRB1*1106 (20%, 17%, and 5%, respectively). On the other hand,
      several common alleles in Wajin (DRB1*1502, 1302, 0803, and 1501) were found at
      relatively low frequencies (1-2%) in Ainu. Previously DRB1*1406 was described as
      a characteristic allele of some Native American or northeast Asian ethnic groups,
      and DRB1*1106 had been found in only two Singapore Chinese and one Korean.
      Principal component analysis of various populations based on HLA class II allele
      frequencies places the Ainu population midway between other east Asian
      populations, including Wajin, and Native Americans. These observations may
      support the hypothesis that the Ainu people are the descendants of some Upper
      Paleolithic populations of northeast Asia from which Native Americans are also
      descended.

PMID- 8876811
TI  - Anemia, genetic diseases, and malaria in prehistoric mainland Southeast Asia.
AB  - The analysis of a sample of skeletons from the 4,000-year-old site of Khok Phanom
      Di on the coast of central Thailand has identified a number of individuals with
      skeletal evidence suggestive of severe anemia. The differential diagnosis of the
      lesions is discussed and the presence of one of the thalassemia syndromes is
      proposed. The implications of this for southeast Asian prehistory are discussed.
      The presence of these conditions has been suggested in previous analyses of
      prehistoric southeast Asian populations, but this is the first population in
      which the evidence, including postcranial responses, is presented in detail.

PMID- 8876812
TI  - Heterogeneity of mitochondrial DNA haplotypes in Pre-Columbian Natives of the
      Amazon region.
AB  - We report the first study of mitochondrial DNA (mtDNA) sequencing from ancestral
      Amerindian populations of the South American continent. Sequencing of the D-loop
      region of mtDNA was carried out for bone fragments from 18 skeletons of Pre
      Columbian Amerinidians. The skeletons were excavated in different archeological
      sites of the Brazilian Amazon region, with dating estimated at 500-4,000 years
      before the present. The sequencing of at least 354 bases permitted the
      identification of 13 haplotypes defined by variation of 26 nucleotide positions.
      Two haplotypes were shared by more than one sample, while 11 haplotypes were
      observed for a single sample. Seven haplotypes observed in 11 individuals (61% of
      the sample) belong to the four haplogroups described by Horai et al. (1993).
      Three samples that shared the transition C-->T in positions 16,223 and 16,278
      formed a fifth haplogroup, which has been previously described in present-day
      Indian populations. Finally, four samples formed a heterogeneous group but each
      haplotype had at least one mutation typically detected in Asian or Mongoloid
      populations. Thus, although only haplotypes shared by Asian populations were
      detected, a wide haplotype variability was observed. If our sample is
      representative of Pre-Columbian South America, the percentage of haplotypes (39%)
      not belonging to the four haplogroups described by Horai is much greater than in
      contemporary indigenous populations. This permits us to suggest that, in addition
      to the postulated bottleneck effect during the migration from Asia to the
      Americas, the depopulation effect started by European colonization in the 16th
      century contributed to the reduction in genetic variability of Amerindians.

PMID- 8876813
TI  - Gender-related factors affecting primate social behavior: grooming, rank, age,
      and kinship in heterosexual and all-male groups of stumptail macaques.
AB  - The structure of grooming relations was studied in three captive groups of
      stumptail macaques, two heterosexual (consisting mainly of females) and one all
      male. Compared to the heterosexual groups, social hierarchy in the all-male group
      was less linear, and agonistic and peaceful activity of low-ranking individuals
      toward high-ranking ones was higher. In addition, in the all-male group received
      grooming was more variable than performed grooming and showed stronger dependence
      on age. No effect of maternal kinship was found in the all-male group, and
      individual preferences were also less marked in this group than in heterosexual
      groups. These differences tend to be related to dominance style and dispersal
      patterns.

PMID- 8876814
TI  - Climbing, brachiation, and terrestrial quadrupedalism: historical precursors of
      hominid bipedalism.
AB  - The vertical-climbing account of the evolution of locomotor behavior and
      morphology in hominid ancestry is reexamined in light of recent behavioral,
      anatomical, and paleontological findings and a more firmly established phylogeny
      for the living apes. The behavioral record shows that African apes, when
      arboreal, are good vertical climbers, and that locomotion during traveling best
      separates the living apes into brachiators (gibbons), scrambling/
      climbing/brachiators (orangutans), and terrestrial quadrupeds (gorillas and
      chimpanzees). The paleontological record documents frequent climbing as an
      ancestral catarrhine ability, while a reassessment of the morphology of the torso
      and forelimb in living apes and Atelini suggests that their shared unique
      morphological pattern is best explained by brachiation and forelimb suspensory
      positional behavior. Further, evidence from the hand and foot points to a
      terrestrial quadrupedal phase in hominoid evolution prior to the adoption of
      bipedalism. The evolution of positional behavior from early hominoids to hominids
      appears to have begun with an arboreal quadrupedal-climbing phase and proceeded
      though an orthograde, brachiating, forelimb-suspensory phase, which was in turn
      followed by arboreal and terrestrial quadrupedal phases prior to the advent of
      hominid bipedality. The thesis that protohominids climbed down from the trees to
      become terrestrial bipeds needs to be reexamined in light of a potentially long
      history of terrestriality in the ancestral protohominid.

PMID- 8876815
TI  - The crescent of foramina in Australopithecus afarensis and other early hominids.
AB  - The crescent of foramina of the cerebral surface of the sphenoid bone (superior
      orbital fissure, foramen rotundum, foramen ovale, foramen spinosum) differs
      morphologically in the African great apes and modern humans. New discoveries of
      Australopithecus afarensis at Hadar, Ethiopia, draw attention to the similarity
      of the crescent, particularly the "foramen" shape of the superior orbital fissure
      and its close proximity to the foramen rotundum, in this species, the African
      apes, and many other primates. Australopithecus africanus also shows this
      primitive pattern, whereas "robust" australopiths and humans share a
      configuration in which a true, laterally extended superior orbital fissure
      intervenes between the greater and lesser wings of the sphenoid and a broad
      bridge of bone separates the fissure from the foramen rotundum. This shared
      morphology may be added to the list of putative "robust" australopith-Homo
      synapomorphies.

PMID- 8876816
TI  - Phytolith analysis on dental calculus, enamel surface, and burial soil:
      information about diet and paleoenvironment.
AB  - Silica phytoliths (microscopic remains originating in plant tissues) have been
      identified on the enamel surface and dental calculus of a sample of teeth
      selected from well preserved skeletons from a Late Roman necropolis in Tarragona
      (Spain). Phytoliths were observed by scanning electron microscopy (SEM) and their
      siliceous nature was confirmed by X-ray microanalysis. The phytoliths were
      compared to those of soil samples from both the areas of the tombs corresponding
      to the abdomen and the periphery of the skeletons, and were classified
      taxonomically by comparison with a large collection of silica particles from
      modern plants in the Mediterranean area. Most of the phytoliths identified on the
      enamel and the dental calculus belong to the family of Poaceae, while the
      phytoliths from the abdominal area belong to Poaceae, Leguminosae, Cyperaceae,
      and Chenopodiaceae. Results are concordant with archaeological, ecological, and
      historical data from the same site, and with the human Mediterranean diet. If
      done properly, the study of phytoliths can provide direct information about the
      vegetable diet of past human populations, and could be applied to the study of
      human fossils.

PMID- 8876817
TI  - Transverse (Harris) lines in Irish archaeological remains.
AB  - Transverse lines were examined in 633 long bones from 73 individuals exhumed from
      two burial sites in the Republic of Ireland: Waterford City and Tintern Abbey.
      The burials cover four distinct periods between the 11th and 17th centuries.
      Lines were most numerous in the tibia, especially in the distal segment, and were
      not seen in the humerus nor the proximal part of the femur. The number of lines
      varied between the proximal and distal segments of each long bone, and though
      apparently equal in number across the midline, there were significant differences
      in the incidence of lines between corresponding pairs of bones. Thus, it is
      unwise to rely on the results of a single bone or one type of long bone alone
      either to indicate the health status of an individual, or as the basis for
      assessing the health status of a small population. Such results should be used
      only in association with other indicators.

PMID- 8876818
TI  - The anatomy of the heart revisited.
AB  - BACKGROUND: There is a marked conservative tendency to be found in anatomic
      descriptions, with a seeming reluctance on the part of acknowledged experts to
      test new theories by returning to direct studies of gross anatomy. This tendency
      has become manifest to us during recent attempts to review the structure and
      function of the heart. METHODS: We have reviewed our recent experience in trying
      to describe the structure and development of the atrial septum and arterial
      roots, attempting at the same time to establish the place of semantic as opposed
      to morphologic factors in disagreements on these topics. RESULTS: Dissection of
      the structures separating the right atrium from the left atrium shows a
      fundamental difference between the infolded superior rim of the oval foramen,
      made up of the atrial walls, versus the make up of the sinus and atrioventricular
      septums, which are true septal structures. Analysis of the arterial roots shows
      that the major feature is the semilunar attachment of the valvar leaflets, an
      arrangement not ideally described in terms of an annulus. CONCLUSIONS:
      Understanding of details of cardiac anatomy, as set out in standard textbooks, is
      hindered by a reluctance on the part of some to accept material presented on the
      basis of straightforward gross dissection. Instead, there is a seeming desire to
      depend on conventional wisdom, often unsupported by anatomic fact. Such
      controversies can be ameliorated by appropriate recognition to contributions of
      gross morphology and by using simple words to describe the observed anatomic
      features.

PMID- 8876819
TI  - Ultrastructural recognition of gap junctions between melanocytes in human
      vestibular organs by tannic acid containing fixative preparation and freeze
      fracture technique.
AB  - BACKGROUND: The purpose of the present study was to obtain additional information
      about the ultrastructural characteristics of gap junctions between melanocytes in
      human vestibular organs by using various ultrastructural techniques. METHODS: All
      materials were obtained from patients with vestibular schwannoma. Glutaraldehyde
      fixed specimens and specimens treated with fixative containing glutaraldehyde and
      tannic acid were processed for conventional ultrathin transmission electron
      microscopic (TEM) examination. Others were prepared for freeze-fracture replica
      and examined by TEM. RESULTS: Gap junctions were present between adjacent
      subepithelial melanocytes. The gaps between the inner leaflets of the apposed
      plasma membranes at the gap junctions were 10-12 nm, and the gaps between the
      outer leaflets were 2-4 nm. The intercellular space between the apposed plasma
      membranes of gap junctions showed the deposition of high electron-dense material
      in specimens prepared with fixative containing glutaraldehyde and tannic acid. At
      the highest magnification specimens fixed by glutaraldehyde with or without
      tannic acid and cut obliquely to the plasma membranes showed periodic
      substructures with constant repeating lattices or a small porous structure at the
      junctions. Study by freeze fracture revealed that these gap junctions between
      melanocytes consisted of 100-200 aggregations of connexon particles that were
      approximately 8.8 nm in diameter. CONCLUSIONS: We suggest that melanocytes may
      construct a cellular network involved in the maintenance of the homeostasis of
      human vestibular organs through the intimate transmission of various signals or
      intercellular informations via well-developed gap junctions.

PMID- 8876820
TI  - Skin morphology and cytology in marine eels adapted to different lifestyles.
AB  - BACKGROUND: Moray eels (Muraenidae, Pisces) are among the largest benthic
      predators of littoral habitats, particularly in warm seas and coral reefs. They
      seek food either by olfaction or visually, moving across the pebbles and rocks.
      Their skin forms a strong, protective layer. This study examines the comparative
      morphology and cytology of the skin of moray eels adapted to such lifestyles.
      METHODS: The studied eels were collected in the Gulf of Aqaba, Red Sea and
      sacrificed by an overdose of MS222. Skin selections from different body sites
      were dissected and fixed for light and electron microscopy. RESULTS: The skin of
      moray eels (Siderea grisea, Lycodontis nudivomer, Gymnothorax undulata, G.
      hepaticus, Rhinomuraena amboensis) and the heterocongrid garden eel (Gorgasia
      sillneri) reveal considerable adaptation of the integument to their different
      lifestyles, on and within the various bottom substrata. All the eels studied
      featured skin comprising a multilayered, stratified epidermis and a compact,
      collagenous dermis, with thickness of up to 2 mm, much thicker than that observed
      in their free-swimming relatives. The thickness and cytology of the two skin
      layers differ in the various species on different body sites within the same
      species and also changes with age. Pronounced differences were observed in the
      number and type of mucus-producing cells in the epidermis. In S. grisea, the
      entire body is covered by a multiple layer of goblet cells, whereas in G.
      sillneri, sacciform cells predominate, particularly on the caudal part of the
      body where they form an uninterrupted layer, replacing the supporting cells that
      surround them. These cells are also dominant in R. amboensis. The two latter
      species are sand-dwelling and the copious production of slime from these cells
      enables the adhesion of sand granules to their burrow walls. In Gorgasia, a
      special morphological adaptation was also observed in its pointed tail-end where
      the very strong dermal collagen forms a rigid device for digging tail-first into
      the sand. CONCLUSION: The differing thicknesses and cytological developments in
      the skin of marine eels protect these crawling and digging creatures against
      abrasive interaction with their sea bottom habitat.

PMID- 8876821
TI  - Effects of caffeine on bone cells and bone development in fast-growing rats.
AB  - BACKGROUND AND METHODS: Caffeine exerts harmful effects on fetal and suckling
      rats. To elucidate the effects of caffeine on bone in growing rats further, dams
      were fed normal laboratory chow until delivery. At birth, the litters were
      combined and eight pups were randomly assigned to each dam. Dams with the
      combined litters were divided into two groups. Dams of group 1 received a 20%
      protein diet as a control, and dams of group 2 received the 20% protein diet
      supplemented with caffeine (4 mg/100 g b.w.). Pups from both groups were killed
      on days 11, 15, 22, and 50. Parameters studied were ultrastructure of femoral
      osteoblasts, osteocytes, and osteoclasts; the number of osteocytes per area of
      bone in femoral histological cross sections; structural remodeling and shape of
      the lateral tibial metaphysis as revealed by scanning electron microscopy; and
      plasma Cu and Zn concentrations. RESULTS: Rats in the caffeine groups had
      significantly fewer osteocytes per area of femoral cross section, retarded
      structural remodeling of the lateral tibial metaphysis, osteoblasts and
      osteocytes with disrupted swollen mitochondria, and decreased plasma Cu and Zn
      levels when compared with controls. CONCLUSIONS: These results indicate that if
      young, rapidly growing rats are exposed to caffeine, disruption of osteoblasts
      and retarded bone development occur, which could be related to the decreased
      plasma Cu level in the young animals.

PMID- 8876822
TI  - Trabecular and endocortical bone surfaces in the rat: modeling or remodeling?
AB  - BACKGROUND: There is conflicting evidence as to whether bone resorption and bone
      formation are coupled in the site-specific manner that is typical of bone
      remodeling in the rat. The aim of this study was to elucidate this controversy
      further by analysis of tibial and vertebral cancellous and endocortical bone in
      rats of different age groups with a combination of in vivo fluorochrome labeling
      with cement line staining. METHODS: After multiple in vivo fluorochrome labeling,
      groups of female Fischer-344 rats were killed at 3, 6, 9, and 12 months of age,
      and the first lumbar vertebrae and the proximal tibiae were processed
      undecalcified for bone histomorphometry. By comparing fluorochrome labeling and
      the contour of cement lines in serial sections, cancellous and endocortical bone
      formation sites were classified as "remodeling," "modeling," or "uncertain."
      RESULTS: In vertebral cancellous bone, remodeling was the main turnover activity
      in all age groups, increasing from 70.4 +/- 2.2% (mean +/- SEM) in 3-month-old
      rats to 91.0 +/- 2.4% in 12-month-old rats. The percentage of modeling sites
      decreased from 17.1 +/- 1.7% at age 3 months to 4.67 +/- 1.84% at age 12 months.
      In the proximal tibial metaphysis of 3-month-old rats, 61.6 +/- 3.6% of all
      trabecular bone-forming sites were classified as modeling and 21.1 +/- 3.1% as
      remodeling sites. In the 12-month-old rats, 66.3 +/- 3.4% were classified as
      remodeling and 16.0 +/- 3.1% as modeling sites. A similar trend toward augmented
      portions of remodeling with increasing age was observed in tibial and vertebral
      endocortical bone-formation sites. CONCLUSIONS: The present study suggests that,
      similar to higher mammals, the prevailing activity in vertebral and tibial
      cancellous bone of aged rats is remodeling. In the rapidly growing proximal tibia
      of 3-month-old rats, however, most of the cancellous bone-forming sites were
      minimodeling sites.

PMID- 8876823
TI  - Evidence of structural and material adaptation to specific strain features in
      cortical bone.
AB  - BACKGROUND: Functionally induced strains provide epigenetic signaling for bone
      modeling and remodeling activities. Strain gauge documentation of the equine
      third metacarpal reveals a neutral axis passing through the craniolateral cortex,
      resulting in a narrow band of cortex loaded predominantly in tension, with the
      remainder of the cortex experiencing a wide range of compression strain
      magnitudes that are maximal in the caudomedial cortex. This predictable strain
      pattern provides a model for examining the hypothesis that strain mode,
      magnitude, and strain energy density are potential correlates of compact bone
      structural and material organization. METHODS: Structural and material variables
      were quantified in nine equine (standard breeds) third metacarpals for comparison
      with the in vivo strain milieu that was evaluated in thoroughbred horses. The
      variables quantified included secondary osteon population density (OPD),
      fractional area of secondary bone (FASB), fractional area of porous spaces,
      collagen fiber orientation, mineral content (% ash), and cortical thickness. Each
      bone was sectioned transversely at 50% of length, with subsequent quantification
      of eight radial sectors and three intracortical regions (periosteal, middle,
      endosteal). Linear regression analysis compared these variables to magnitudes of
      corresponding regional in vivo longitudinal strain, shear strain, and strain
      energy density values reported in the literature. RESULTS: The craniolateral
      ("tension") cortex of this bone is distinguished by its 30% lower FASB and with
      the lateral cortex exhibits 20% darker gray level (more longitudinal collagen)
      compared with the average of all other locations. Conversely, the remaining
      ("compression") cortices as a group have a high OPD, are more extensively
      remodeled, and contain more oblique-to-transverse collagen. The caudal cortices
      (caudomedial, caudal, caudolateral) are significantly thinner (P < 0.01) and have
      4% lower mineral content (P < 0.05) than all other locations. Moderately strong
      correlations exist between collagen fiber orientation and normal strain (r =
      0.752) and shear strain (r = 0.555). When normal and shear strains were
      transformed to their respective absolute values, thus eliminating the effects of
      strain mode (tension vs. compression), these correlation coefficients decreased
      markedly. CONCLUSIONS: Collagen fiber orientation is related to strain mode and
      may function to accentuate rather than attenuate bending. These differences may
      represent adaptations that function synergistically with bone geometry to promote
      a beneficial strain distribution and loading predictability during functional
      loading.

PMID- 8876824
TI  - Immunocytochemical colocalization of desmin and vimentin in human fetal skeletal
      muscle cells.
AB  - BACKGROUND: Desmin and vimentin are the major intermediate filaments in muscle.
      They have been extensively studied in animal experiments. This study is the first
      to identify the distribution and to analyse the correlation of desmin and
      vimentin in human fetal skeletal muscle. Vimentin might be replaced by or
      transformed into desmin during myogenesis in chick embryo, although the precise
      process remains to be elucidated. The aim of this report is to evaluate the ratio
      of desmin to vimentin in human fetal muscle. METHODS: By double-labeling
      immunoelectron microscopy, desmin and vimentin intermediate filaments were
      localized in developing skeletal muscles of 20-29-week-old human fetuses. The
      ratio of desmin and vimentin was analyzed statistically. RESULTS: Two sizes of
      colloidal gold particles, 5 nm (vimentin) and 10 nm (desmin), were distributed
      along the intermediate filaments. The commonest distance between gold particles
      was approximately 40-50 nm. Desmin and vimentin labeled with gold particles were
      arranged very close together in the same intermediate filament. The ratio of
      vimentin to desmin varied but the amount of vimentin decreased progressively from
      the undifferentiated myoblast to the differentiated myocytes. As the fetuses
      developed, desmin increased and vimentin decreased. Desmin and vimentin
      intermediate filaments were identified in the intermyofibrils of differentiated
      myocytes, in subsarcolemmal space, and in myoblast. CONCLUSIONS: Desmin and
      vimentin were colocalized in the same intermediate filaments. More vimentin
      existed in the less differentiated myocytes, although a small number of desmin
      filaments were already found in undifferentiated myoblasts. These intermediate
      filaments may not only connect myofibril bundles, cell organelles, and cell
      membrane but also provide a basis for myofibrillogenesis that is similar to
      relation between connective fibers and parenchymal cells.

PMID- 8876825
TI  - Actin-binding proteins undergo major alterations during the plasma membrane
      transformation in uterine epithelial cells.
AB  - BACKGROUND: The apical surface of uterine epithelial cells undergoes a dramatic
      transformation during early pregnancy. Previous studies have shown that
      cytoskeletal actin microfilaments are associated with this transformation, but
      little is known of the role played by actin-binding proteins or which of the many
      described in other cell types are present in uterine epithelial cells. METHODS:
      Immunohistochemical staining using monoclonal antibodies raised against four
      different actin-binding proteins (alpha-actinin, tropomyosin, gelsolin, and
      vinculin) was used to study the changing distribution of these proteins in
      uterine epithelium during early pregnancy in the rat. RESULTS: Findings indicated
      the presence of all four of the actin-binding proteins in the uterine epithelium.
      The distribution of tropomyosin remained unchanged over the period of early
      pregnancy. Gelsolin and alpha-actinin displayed similarity in distribution. Day 1
      showed an apicobasal localisation of reaction product, which by day 6 of
      pregnancy had concentrated into a thick band across the luminal surface of the
      cells. Vinculin staining was a diffuse band at the level of the basal plasma
      membrane at day 1 and became a diffuse faint band across the apical part of the
      cells on day 6. CONCLUSIONS: This study confirms the presence of actin-binding
      proteins in uterine epithelial cells, and these findings are discussed in light
      of known ultrastructural alterations in the uterine epithelium during early
      pregnancy. Elucidation of the role of the actin-based cytoskeleton in the uterine
      epithelium may further our understanding of the dynamics of this unique
      environment that allows the implantation of a blastocyst.

PMID- 8876826
TI  - Human complement regulator expression by the normal female reproductive tract.
AB  - BACKGROUND: The membrane-associated proteins that regulate human complement
      activation are ubiquitously expressed and function cooperatively to protect cells
      from autologous complement damage. For classical and alternative pathways, the
      primary regulators at the stage of C3 proteolysis and deposition are membrane
      cofactor protein (MCP; CD46) and decay-accelerating factor (DAF;CD55), whereas
      protectin or CD59 regulates terminal component assembly. There is increasing
      awareness in reproductive, tumor, and transplantation immunology of the
      conventional and non-complement roles of these proteins. The human reproductive
      system may serve as a model of the non-complement functions. METHODS: We
      performed immunohistochemical analyses of multiple normal ovaries, fallopian
      tubes, cervices, and uterine corpi by using well-characterized monoclonal
      antibodies to provide a detailed, direct comparison of complement regulator
      expression. RESULTS: Membrane cofactor protein was diffusely and strongly
      expressed on all epithelia and vascular endothelium and was the predominant
      regulator on oocytes. In contrast, decay-accelerating factor had variable
      expression in intensity and distribution on epithelia and was notably absent on
      certain epithelia and oocytes. It was the only regulator present on the
      connective tissue between muscle bundles in the myometrium and the cervix and was
      found on most stroma. CD59, although staining intensity varied, was present on
      virtually all epithelia, vascular tissue, and stroma. CONCLUSIONS: Distinct
      reproducible patterns of complement regulator expression are found throughout the
      female reproductive tract. Differential expression on certain epithelia and
      oocytes may suggest non-complement activities. This comprehensive study should
      provide a basis for further characterization of pathological tissues and
      mechanisms of cellular localization.

PMID- 8876827
TI  - Pulmonary macrophages in birds (barn owl, Tyto tyto alba), domestic fowl (Gallus
      gallus f. domestica), quail (Coturnix coturnix), and pigeons (Columbia livia).
AB  - BACKGROUND: Birds have a limited number of resident macrophages in the normal
      steady-state respiratory tract. The discovery of phagocytes in lavages of lung
      from birds contrasts with findings that phagocytes are seldom seen in
      investigations in situ. An electron microscopic study was performed in the
      respiratory units, the parabronchi, and air capillaries in particular in several
      adult bird species to localize the seat of respiratory macrophages. METHODS: Lung
      tissue of barn owl, domestic fowl, quail, and town and homing pigeons was
      subjected to standard processing for light and electron microscopy after
      immersion fixation, intratracheal instillation, and intravascular perfusion.
      RESULTS: Clusters of macrophages were predominantly housed in the loose
      connective tissue at the floor of atria at the entrance to the infundibula and
      gas-exchange tissue proper. Scattered solitary phagocytes were also found in
      connective tissue of air sacs, interatrial septa, and adventitia of inter- and
      intraparabronchial arteries and veins and in peribronchial lymphoid tissue.
      Phagocytized foreign particulate material mostly consists of hard, dense,
      crystalline formations surrounded by a limiting membrane. The transport of small
      airborne particles occurs via the squamous atrial epithelium to the underlying
      macrophages. The macrophages are often accompanied by mast cells. CONCLUSIONS:
      The present results demonstrate that avian respiratory macrophages are
      predominantly located in atrial connective tissue compartments and do not seem to
      migrate to the airway surfaces.

PMID- 8876828
TI  - Modulation of autotransplanted adrenal gland by endothelin-1: a morphological and
      biochemical study.
AB  - BACKGROUND: Adrenal gland autotransplantation, a model of cortical tissue
      regeneration, provides the reconstruction of distinct functional and
      morphological zonae. A morphological and biochemical study of the adrenal gland
      of adult male rats after autotransplantation and endothelin-1 (ET-1)
      administration was made. METHODS: The technique involved bilateral adrenalectomy
      and placement of pieces of the adrenal gland in a dorsal plane between the skin
      and muscle. The animals were killed 90 days after the autotransplantation and 1
      hr after intravenous ET-1 administration (0.5 microgram/kg body weight). The
      autotransplanted pieces were removed, fixed, and processed for light and electron
      microscopic morphologic studies. Trunk blood was collected for steroid assay.
      RESULTS: Saline-treated control autotransplanted animals showed no remarkable
      differences in adrenal organization; grafts exhibiting a mass of regenerated
      cortical tissue were arranged in nests of glandular cells surrounded by a fibrous
      capsule and intersected by layers of connective tissue. The adrenal medulla was
      systematically absent. Ultrastructure of ET-1-treated animals revealed an inner
      area in the graft, consisting mainly of fasciculatalike cells. Cytoplasmic
      changes were evident, with high variations in mitochondrial size and arrangement.
      Profiles of smooth endoplasmic reticulum sometimes exhibited evidence of
      hypertrophy. Glandular cells in the graft outer area (subcapsular) were almost
      invariably like glomerulosa; however, some of them showed mitochondria with a
      peculiar arrangement of the cristae. "Hybrid" cells with mitochondria resembling
      those of the zona reticularis were also observed in the subcapsular environment.
      ET-1-stimulated animals showed significant increases in plasma corticosterone and
      aldosterone concentrations. CONCLUSIONS: Endothelin-1, previously reported to
      stimulate acutely the aldosterone secretion by the adrenal zona glomerulosa in
      the rat, seems to exert a modulator role on the physiology of adrenal
      autotransplants, their regeneration and secretion.

PMID- 8876829
TI  - Origin of the pulmonary venous orifice in the mouse and its relation to the
      morphogenesis of the sinus venosus, extracardiac mesenchyme (spina vestibuli),
      and atrium.
AB  - BACKGROUND: Human embryology textbooks indicate that the trunks of the pulmonary
      vein and artery originate from the left atrium and aortic sac, respectively,
      based on histological analyses of limited human specimens. However, our studies
      show that the pulmonary venous trunk in the mouse as in other nonhuman
      vertebrates originates from a vascular "sac" at the venous pole, the sinus
      venosus. METHODS: Mouse embryos of 9-11 days gestation were obtained and staged
      according to Theiler's criteria and fixed in Carnoy's solution. Samples were
      embedded in paraffin and serial sections were prepared. RESULTS: Histological
      analysis showed that at day 9.5 the pulmonary venous rudiment was initially
      observed along the left margin in the extracardiac mesenchyme that separated the
      venous pole of the heart from the lung buds. The endothelium of the pulmonary
      vein was continuous, with a vascular sac we identified as sinus venosus based on
      its location immediately posterior to the left sinoatrial fold. The sinus venosus
      became incorporated into the left atrium (days 10-10.5) to form part of the
      posterior atrial wall. Similarly, the pulmonary vein and associated extracardiac
      mesenchyme were "drawn" into the atrium. This extracardiac mesenchyme of the
      venous pole, also called "spina vestibuli" and containing the pulmonary vein at
      its left margin, formed a wedge-shaped invagination within the atrium that
      contributed nonmuscular tissue to the primary atrial septum. CONCLUSIONS: We
      propose that the orifice of the pulmonary vein establishes a link with the left
      side of the atrium as a consequence of a venous sac, the sinus venosus, and its
      associated mesenchyme (in which the root of the pulmonary vein is embedded) being
      incorporated into the atrium.

PMID- 8876830
TI  - Immunohistochemical localization of cell adhesion molecules and cell-cell contact
      proteins during regeneration of the rat optic nerve induced by sciatic nerve
      autotransplantation.
AB  - BACKGROUND: The central nervous system neurons of adult mammals are known to
      regenerate into peripheral nerve autograft. The localization of cell adhesion
      molecules and cell-cell contact proteins were studied during axonal regeneration
      induced by sciatic nerve autotransplantation. METHODS: A sciatic nerve autograft
      was anastomosed to the proximal stump of the transected rat optic nerve.
      Immunofluorescence microscopy, thin sectioning, and immunoelectron microscopy
      with the preembedding method and ultrathin cryosections were used to localize
      cell adhesion molecules (L1; neural cell adhesion molecule, NCAM; myelin
      associated glycoprotein, MAG) and cell-cell contact proteins (connexins 32, 43,
      ZO-1) at 3 days to 4 weeks postoperation. RESULTS: Most regenerating axons
      contacted astrocytes in the optic nerve and Schwann cells in the graft.
      Immunoreactivity of NCAM was widely distributed along the surface of axons,
      astrocytes, Schwann cells, and perineurial cells. The L1 immunoreactivity was
      confined to the interface of axon-astrocyte and of axon-Schwann cell. MAG
      immunoreactivity was seen at the interface of axon and myelin within the graft.
      Connexins 32, 43, and ZO-1 immunoreactivities were observed at contact sites
      between axons and Schwann cells within the graft. CONCLUSIONS: Cell adhesion
      molecules (L1, NCAM, MAG) are localized at the cell surface of regenerating
      axons, astrocytes, and Schwann cells during optic nerve regeneration elicited by
      peripheral nerve graft. Cell-cell contact proteins (connexins 32, 43, ZO-1) are
      present at the interface between axons and Schwann cells in the graft. Our
      results suggest that these molecules are involved in cell adhesion events during
      optic nerve regeneration.

PMID- 8876831
TI  - The sensorineural specializations of the trunk tip (finger) of the Asian
      elephant, Elephas maximus.
AB  - BACKGROUND: The dorsal extension of the tip of the trunk of Asian elephants
      (Elephas maximus), often referred to as "the finger," possesses remarkable
      mechanical dexterity and is used for a variety of special behaviors including
      grasping food and tactile and ultimately chemosensory recognition via the
      vomeronasal organ. The present study describes a unique sensory innervation of
      this specialized region of the trunk. METHODS: The tip of the dorsal aspect of
      the trunk is referred to as the trunk tip finger and has been studied grossly in
      13 living elephants. One tip from a male Asian elephant was obtained for
      histologic study when it was accidentally severed. The tissue was fixed in 10%
      neutral buffered formalin, and portions were either sectioned frozen or embedded
      in paraffin and serial sectioned. Sections were stained with silver in both
      cases. RESULTS: The skin of the trunk tip finger differs from that of the
      surrounding areas; it contains a high density of free nerve endings, numerous
      convoluted branched small corpuscles, and vellus vibrissae that resemble vellus
      hairs, which do not protrude beyond the skin surface. The finger is thus densely
      innervated with three distinctive types of sensory terminals. Corpuscular
      receptors consist of small Pacinian corpuscles and convoluted branched simple
      corpuscles. Both are present in the superficial dermis. Abundant regular
      vibrissae are present in the skin surrounding the trunk tip finger. Short
      vibrissae that do not protrude from the skin surface, referred to as vellus
      vibrissae, are abundant in the finger tip. Both types of vibrissae are innervated
      by hundreds of axons resembling the mystacial vibrissae of rodents. Free nerve
      endings are numerous in the superficial dermis, often making intimate contact
      with the basal cells of rete pegs. CONCLUSIONS: The dorsal finger of the trunk
      tip of Asian elephants has a unique sensory innervation that resembles aspects of
      sensory innervation of mystacial skin of rodents or lip tissue of monkeys. This
      dense sensory innervation can be correlated with the tactile ability of these
      animals to use the trunk finger to grasp small objects for feeding and to insert
      chemically active samples into the ductal orifices of the vomeronasal organ for
      subsequent chemosensory processing.

PMID- 8876832
TI  - Ultrastructure of the crotaline snake infrared pit receptors: SEM confirmation of
      TEM findings.
AB  - BACKGROUND: Crotaline snakes possess a pair of infrared-sensing pit organs that
      aid the eyes in the detection and apprehension of prey. The morphology of the
      receptors in the pit organs has been studied by light and transmission electron
      microscopy, and the ultrastructure of the receptors has been inferred from the
      results of this work. But this theoretical reconstruction has never been
      confirmed by any kind of three-dimensional imaging. METHODS: We treated the
      receptor-containing membrane of the pit organs with potassium hydroxide to remove
      collagen and expose the receptors, which we then viewed by scanning electron
      microscopy. RESULTS: We were able to obtain three-dimensional views of all
      structures previously reported to exist within the receptor-containing membrane:
      terminal nerve masses formed from free nerve endings, supporting Schwann cells
      within the nerve masses, unmyelinated and myelinated nerve fibers, a capillary
      bed, and vacuole cells. CONCLUSIONS: By providing the first three-dimensional
      views of the infrared receptors, we have confirmed that previous theoretical
      reconstructions of the receptors were substantially correct and have provided new
      evidence of the spatial arrangement of the receptors in a monolayer array.

PMID- 8876833
TI  - Sectional anatomy of connective tissue structures in the hindfoot of the newborn
      child and the adult.
AB  - BACKGROUND: The knowledge of the normal anatomy of the newborn hindfoot is
      essential for the understanding of foot deformities. In the present study, we
      investigated tendons, ligaments, and soft tissue structures in the newborn foot.
      METHODS: The sectional anatomy of eight newborn feet was studied in 300-500
      microns-thick sections processed by plastination histology. For comparison, 3-5
      mm-thick plastinated sheets of adult feet were investigated. RESULTS: Our
      specimens show obvious differences of the newborn compared with the adult foot.
      In the subcutaneous adipose tissue, the heel pad and the fat pad of the Achilles
      tendon and the relative size and topography of adipose tissue pads are different.
      Moreover, the course of the flexor hallucis tendon and the insertion pattern of
      the Achilles tendon are distinct. Finally, there are differences in the course
      and in the relative length of some plantar ligaments. CONCLUSIONS: Our data
      reveal that the differences between the newborn foot and the adult foot result
      mainly from the different shape and position of the tarsal bones. Our findings
      are of clinical importance for the evaluation of magnetic resonance imaging in
      the normal infant's foot and in foot deformities.

PMID- 8876834
TI  - Coronary heart disease, stroke, and hypertension in a U.S. national cohort: the
      NHANES I Epidemiologic Follow-up Study. National Health and Nutrition Examination
      Survey.

PMID- 8876835
TI  - Socioeconomic status, ethnicity and obesity in women.

PMID- 8876836
TI  - Race, socioeconomic status, and obesity in 9- to 10-year-old girls: the NHLBI
      Growth and Health Study.
AB  - The purpose of this investigation was to determine whether measures of
      socioeconomic status (SES) are inversely associated with obesity in 9- to 10-year
      old black and white girls and their parents. Subjects were participants in the
      Growth and Health Study (NGHS) of the National Heart, Lung, and Blood Institute.
      Extensive SES, anthropometric, and dietary data were collected at baseline on
      2379 NGHS participants. The prevalence of obesity was examined in the NGHS girls
      and parents in relation to SES and selected environmental factors. Less obesity
      was observed at higher levels of household income and parental education in white
      girls but not in black girls. Among the mothers of the NGHS participants who were
      seen, lower prevalence of obesity was observed with higher levels of income and
      education for white mothers, but no consistent patterns were seen in black
      mothers. Univariate logistic models indicated that the prevalence of obesity was
      significantly and inversely associated with parental income and education and
      number of parents in the household in white girls whereas caloric intake and TV
      viewing were significantly and positively associated with obesity. Among black
      girls, only TV viewing was significantly and positively associated with the
      prevalence of obesity. Multivariate logistic regression models revealed that
      lower parental educational attainment, one-parent household, and increased
      caloric intake were significantly associated with the prevalence of obesity in
      white girls; for black girls, only increased hours of TV viewing were significant
      in these models. It is concluded that socioeconomic status, as measured by
      education and income, was related to the prevalence of obesity in girls, with
      racial variation in these associations. A lower prevalence of obesity was seen at
      higher levels of socioeconomic status in white girls, whereas no clear
      relationship was detected in black girls. These findings raise new questions
      regarding the correlates of obesity in black girls.

PMID- 8876837
TI  - A prospective study of colon and rectal cancer among Hawaii Japanese men.
AB  - The goals of this study were to assess the association of diet, alcohol, smoking,
      and other life-style factors with the risk of colon and rectal cancer and to
      examine the differences in the risk factors associated with each cancer site.
      Information on diet, alcohol, smoking, and other life-style factors was obtained
      from 7945 Japanese-American men who were living in Hawaii and examined from 1965
      through 1968. After 174,514 person-years of observation, 330 incident cases of
      colon cancer and 123 incident cases of rectal cancer were diagnosed by histology.
      The risk of both colon and rectal cancer increased with age, alcohol intake, and
      pack-years of cigarette smoking. For colon cancer, there was also a direct
      association with body mass index and heart rate, while an inverse association was
      observed with serum cholesterol, intake of monounsaturated fatty acid, and
      percentage of calories from fat. For rectal cancer, the risk decreased with an
      increase in the intake of carbohydrates as percentage of calories. These findings
      suggest that some of the risk factors for colon cancer are different from those
      for rectal cancer.

PMID- 8876838
TI  - The lack of association of marijuana and other recreational drugs with
      progression to AIDS in the San Francisco Men's Health Study.
AB  - We evaluated the associations of specific recreational drugs and alcohol with
      laboratory predictors of AIDS at entry into the San Francisco Men's Health Study
      (SFMHS) in 1984 and with the development of the acquired immunodeficiency
      syndrome (AIDS) during 6 years of follow-up. Marijuana use was associated with a
      decreased rate of progression to AIDS in the univariate analysis (RR = 0.7; P =
      0.01). Marijuana use was more common among individuals with elevated HIV viral
      core protein antibody (p24Ab) titer (> 1:16) at baseline (P = 0.03); this finding
      suggests that marijuana users were healthier at baseline. When the data were
      adjusted for p24 Ab and other laboratory parameters, no association with
      progression to AIDS was observed for marijuana, suggesting that the observed
      univariate result was due to a difference in HIV-related disease at the time of
      enrollment. No statistically significant associations were observed for nitrites,
      methylene dioxyamphetamines, ethyl chloride, downers, cocaine, stimulants,
      narcotics, or psychedelic drugs. These data suggest no substantial association
      between use of these drugs and the development of AIDS among HIV-infected men.

PMID- 8876839
TI  - The role of socioeconomic status and serum fatty acids in the relationship
      between intake of animal foods and cardiovascular risk factors.
AB  - Little is known regarding the relationship of serum fatty acids to cardiovascular
      risk factors in Nigerian populations. Civil servants with higher socioeconomic
      status (SES) in Nigeria appear to be in cultural transition toward a more
      Westernized lifestyle. For this study the food intakes of 397 civil servants were
      estimated from two 24-h recalls. Fatty acids in serum total lipids were measured
      in both absolute weight concentration and percentage composition. Daily meat
      intake was 43.5 g, and fish intake was 70.5 g. The intakes of meat, eggs, and
      milk were higher in high SES Nigerians than in low SES Nigerians. The
      concentration of total fatty acids (TFA, the sum of 12 serum fatty acids) was
      also higher in high SES men and women, as compared with low SES men and women
      (2064, 2060, 1831, and 1776 mg/L, respectively). There were significant direct
      associations between meat intake and serum level of arachidonic acid, and between
      fish intake and serum levels of eicosapentaenoic acid and docosahexaenoic acid.
      TFA was positively associated with cholesterol, low-density-lipoprotein
      cholesterol (LDLc), and triglycerides across gender and SES groups after
      adjustment for body mass index, fasting insulin level, and age. Nigerian women
      were compared with two groups of American women. We concluded that fatty acids in
      absolute weight concentration reflected the amount of fat intake. The level of
      TFA was directly related to cardiovascular risk factors in Nigerians. Follow-up
      of such populations in cultural transition can facilitate the understanding of
      the true roles of animal food intake in the early evolution of atherosclerosis.

PMID- 8876840
TI  - Cigarette smoking and leukocyte subpopulations in men.
AB  - Because of previously reported associations among the total leukocyte count,
      cigarette smoking, and risk of cardiovascular disease, we examined the relation
      of cigarette smoking to various leukocyte subpopulations among 3467 men aged 31
      to 45 years. The median total leukocyte count was 36% higher (7840 vs. 5760
      cells/mL) among current cigarette smokers than among men who had never smoked,
      and both stratification and regression analyses were used to examine independent
      associations with leukocyte subpopulations. At equivalent counts of other
      subpopulations, CD4+ lymphocytes and neutrophils were the cell types most
      strongly associated with cigarette smoking; each standard deviation change in
      counts of these subpopulations increased the odds of current (vs. never) smoking
      by approximately threefold. Furthermore, whereas 15% of the 238 men with
      relatively low (< 25 percentile) counts of both neutrophils and CD4+ lymphocytes
      were cigarette smokers, 96% of the 249 men with relatively high counts of both
      subpopulations were current smokers. Counts of T lymphocytes also tended to be
      higher among the 32 men with self-reported ischemic heart disease than among
      other men. These results, along with previous reports of immunologically active T
      lymphocytes in atherosclerotic plaques, suggest that this subpopulation may be of
      particular interest in studies examining the relation of leukocytes to
      cardiovascular disease.

PMID- 8876841
TI  - Migration status, socioeconomic status, and mortality rates in Mexican Americans
      and non-Hispanic whites: the San Antonio Heart Study.
AB  - It has been claimed that Mexican Americans have a favorable mortality experience
      despite their low socioeconomic status (SES). The present study compared all
      cause mortality of non-Hispanic whites with that of United States-born and
      foreign-born (i.e., born in Mexico) Mexican Americans. Subjects were 3735
      residents of San Antonio, TX, who were followed-up for 7-8 years. The sex-age
      adjusted death rates per 1000 person-years were higher for United States-born
      Mexican Americans (5.7) than for non-Hispanic whites (3.8) or for foreign-born
      Mexican Americans (3.6). Foreign-born Mexican Americans had the lowest
      socioeconomic status (SES), and non-Hispanic whites had the highest SES. After
      adjustment for SES, the mortality ratio for United States-born Mexican Americans
      compared with foreign-born Mexican Americans was 1.9 (95% confidence interval,
      1.0-3.5), while the ratio for United States-born Mexican Americans compared with
      non-Hispanic whites was 1.0 (95% confidence interval, 0.7-1.6). Stratified
      analysis revealed that those in the lowest SES tertiles had threefold greater
      risk of death than those in the highest tertiles among both United States-born
      Mexican Americans and non-Hispanic whites (test for trend, P < 0.001). These data
      suggest that lower SES is strongly associated with increased mortality. After
      adjustment for SES, mortality rates were similar for United States-born Mexican
      Americans and non-Hispanic whites. Foreign-born Mexican Americans had the lowest
      mortality rates of the three groups.

PMID- 8876842
TI  - Current estrogen-progestin and estrogen replacement therapy in elderly women:
      association with carotid atherosclerosis. CHS Collaborative Research Group.
      Cardiovascular Health Study.
AB  - The cardioprotective effects of combined estrogen/progestin replacement therapy
      have been questioned. Therefore, we have compared carotid arterial wall
      thickening and the prevalence of carotid stenosis in elderly women (> or = 65
      years old) currently using replacement estrogen/progestins (E + P) with arterial
      pathology and its prevalence in women using unopposed estrogens (E). This cross
      sectional study used baseline data from all 2962 women participating in the
      Cardiovascular Health Study, a population-based study of coronary heart disease
      and stroke in elderly adults. Users of hormone replacement therapy (HRT) were
      categorized as never (n = 1726), past (n = 787), current E (n = 280), or current
      E + P (n = 73). Maximal intimal-medial thicknesses of the internal and common
      carotid arteries and stenosis of the internal carotid arteries were measured by
      ultrasonography. Current E + P users resembled current E users in most respects,
      although some lifestyle factors were more favorable among E + P users. Current E
      + P use and current E use (as compared with no use) were associated with smaller
      internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05,
      respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03;
      and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid
      stenosis (> or = 1% vs. 0%); OR = 0.61; 95% confidence interval [CI]: 0.36 to
      1.01; and OR = 0.91, 95% CI: 0.67 to 1.24, respectively), after adjustment for
      current lifestyle and risk factors. When both groups of current HRT users were
      compared, there were no significant differences in carotid wall thicknesses or
      prevalence of carotid stenosis. For this sample of elderly women, both current E
      + P therapy and current E therapy were associated with decreased measures of
      carotid atherosclerosis. These measures did not differ significantly between the
      two groups of HRT users.

PMID- 8876843
TI  - Lipoprotein(a) and its correlates in Japanese and U.S. population samples.
AB  - To examine whether serum levels of lipoprotein(a) [Lp(a)], a potential coronary
      risk factor, are higher in Caucasian-Americans than in Japanese, a circumstance
      that would correspond to the higher mortality from coronary heart disease in the
      United States than in Japan, we analyzed serum Lp(a) levels in 300 nonsmoking men
      and women aged 47-69 years. Participants were drawn from two population-based
      samples: rural Japanese living in Akita and Caucasians living in Minneapolis-St.
      Paul, MN. Geometric mean and median serum Lp(a) concentrations were higher (P <
      0.05) in Japanese than in Caucasians for both men (difference in geometric mean =
      3.2 mg/dL) and women (difference = 5.3 mg/dL). There was however, no racial
      difference in the proportion of elevated Lp(a) concentrations (i.e., > or = 30
      mg/dL) in either sex. Alcohol intake was inversely correlated with Lp(a) levels
      in Japanese men, who had a high average alcohol intake, but not in other sex and
      racial groups. Serum Lp(a) was nonsignificantly but consistently correlated with
      plasma fibrinogen and LDL-cholesterol for all sex and racial groups. With
      adjustment for alcohol intake, LDL-cholesterol, and plasma fibrinogen, the
      Japanese-Caucasian difference in geometric mean Lp(a) values was even larger for
      men and was not changed for women. Results of the present study do not support
      the hypothesis that racial differences in Lp(a) concentrations contribute to the
      higher mortality rate from coronary heart disease in the United States than in
      Japan.

PMID- 8876844
TI  - Correlates of uric acid and its association with asymptomatic carotid
      atherosclerosis: the ARIC Study. Atherosclerosis Risk in Communities.
AB  - The correlates of serum uric acid and the association of uric acid with carotid
      intimal-medial thickness (an early measure of atherosclerosis) were investigated
      in participants of the baseline examination of the Atherosclerosis Risk in
      Communities (ARIC) Study. The study sample included 6522 women (74% white) and
      4966 men (79% white) who were aged 45 to 64 years at baseline (1986-1989). Those
      with prevalent coronary heart disease or previous stroke and those taking
      uricosuric medication were excluded. The mean (SD) uric acid concentration was
      5.9 (1.5) mg/dL. It was highest among black men 45-54 years old (6.9 [1.5]
      mg/dL), and lowest in white women aged 45-54 years old (5.0 [1.2] mg/dL). The
      uric acid level was positively correlated in both sexes with a variety of health
      related factors, most notably body mass index, creatinine, triglycerides,
      diuretic use, alcohol intake, hypertension, diabetes, and insulin levels. In a
      linear regression model adjusting for age and ARIC center, the level of uric acid
      was directly and significantly associated with B-mode ultrasound carotid intimal
      medial thickness in women and white men (but not in black men). However, when
      known risk factors for atherosclerotic disease and relevant behavioral and
      biological correlates of uric acid were controlled for in multivariate analysis,
      the association of uric acid with this early measure of atherosclerosis became
      negligible in white women and much weaker and not statistically significant in
      black women and white men. Thus, uric acid itself may not be a risk factor for
      atherosclerosis. Future analysis of cardiovascular events in the ARIC Study will
      further elucidate the role of uric acid in atherosclerotic disease.

PMID- 8876845
TI  - Western blot banding patterns of HIV rapid progressors in the U.S. Navy
      Seropositive Cohort: implications for vaccine development. Navy Retroviral
      Working Group.
AB  - Although human immunodeficiency virus (HIV) infection is progressive, the rate of
      decline in CD4+ lymphocyte counts varies. The role of immune system components in
      limiting HIV infection has yet to be defined, but a previous report on the U.S.
      Navy HIV Seropositive Cohort reported that strong reactivity in the anti-p55
      (core precursor), p24 (core) and p53 (reverse transcriptase) Western blot bands
      was associated with higher CD4+ lymphocyte counts at the first clinical
      evaluation for HIV. The previous report examined the cross-sectional association
      between Western blot banding patterns and initial CD4+ lymphocyte counts. This
      report examines the association between these banding patterns in individuals who
      progressed rapidly as compared with patterns of patients who did not, based on
      their trends in repeated CD4+ lymphocyte counts as a marker of progression. Rapid
      and slower progressors were identified from a cohort of 3414 Navy and Marine
      Corps personnel who had a first positive HIV Western blot during 1986-1991. For
      purposes of this study, rapid progressors were defined as individuals whose CD4+
      lymphocyte counts declined to < 500 cells/mm3 within 1 year of seroconversion. A
      total of 325 individuals met these criteria. A comparison group of 63 slower
      progressors also was identified; this group consisted of those whose CD4+
      lymphocyte counts remained at > or = 500 cells/mm3 for a minimum of 5 years of
      follow-up after their first positive Western blot. Rapid progressors were
      slightly younger than slower progressors and were more likely to be never married
      but did not differ significantly from slower progressors in race or sex. Rapid
      progressors had weaker reactivity in the anti-p55 core precursor (P < 0.0001),
      p15 core (P < 0.01), gp41 transmembrane (P < 0.01) and p31 endonuclease (P <
      0.05) bands on the Western blot. The odds ratio for rapid progressor status
      associated with weak or absent reactivity was 7.8 in the anti-p55 band and ranged
      from 2.0 to 3.2 in the anti-p31, p15, and gp41 bands. These associations remained
      significant after adjustment for age, race, and sex. The p55 association
      persisted in repeated Western blots during routine clinical evaluation during a
      period of 5 years after the first positive Western blot. It was concluded that
      several possible explanations may account for the weaker reactivity of rapid
      progressors: (i) weak anti-p55 reactivity might have been a marker of early
      immune system damage; (ii) high concentrations of p55 or related proteins in the
      serum may have bound the available anti-p55 antibodies in rapid progressors,
      making them difficult to identify on the Western blot; or (iii) lack of anti-p55,
      p15, gp41, or p31 reactivity might have allowed more rapid progression.

PMID- 8876846
TI  - Trends in cardiovascular disease incidence and survival in the elderly.
AB  - This study compared the age-specific incidence, postdiagnostic survival, and
      mortality for cardiovascular disease (CVD) in two cohorts of people aged 65 years
      and older. All subjects were members of a large prepaid health maintenance
      organization. The influence of changes in CVD risk factors on these rates also
      was evaluated. Trends in prevalence, incidence, postdiagnostic survival, and
      mortality for CVD were examined in both cohorts in 1971 and 1980. Myocardial
      infarction (MI), angina pectoris, stroke, and congestive heart failure (CHF) were
      included as CVD outcomes in this analysis. Nine-year prospective data on these
      diagnoses were abstracted from medical records and computerized hospitalization
      records for both cohorts. Age-sex-adjusted cardiovascular mortality was lower for
      both sexes by approximately 20% in the 1980 cohort. Overall survival did not
      change, whereas cancer mortality increased by 76% in women and 36% in men. With
      the exception of stroke, there was no increase in age-adjusted or age-specific
      prevalence. In men, the age-adjusted prevalence of stroke in men was 24% higher
      in the 1980 cohort. Age-adjusted 9-year incidence of MI, angina pectoris, stroke,
      and CHF did not change between cohorts in either sex Postdiagnostic, age-adjusted
      mortality for men with incident stroke was 24% lower in the 1980 cohort, and
      Postdiagnostic, age-adjusted mortality for men with incident angina was 35% lower
      in the 1980 cohort. Adjustment for risk factors measured at or before baseline
      had little influence on cohort differences in CVD incidence or duration of
      survival after CVD diagnosis. This study confirms other research showing a
      decline in CVD mortality over the past 20 years. These findings suggest that
      prevalent angina pectoris is increasing in men, and that survival with stroke and
      with angina is improving in men. Later diagnosis of incident CHF in men suggests
      that prevention and early detection may be postponing the development of more
      serious disease.

PMID- 8876847
TI  - Safer sex behavior and alcohol consumption. Research Group of the Swiss HIV
      Prevention Study.
AB  - To test the hypothesis that safer sex procedures are less consistently observed
      by persons under the influence of alcohol, data from the Swiss human
      immunodeficiency virus (HIV) Prevention Study (HIPS) were evaluated. HIPS is a
      large prospective cohort study involving 724 HIV-negative and mainly heterosexual
      subjects who entertain casual sexual contacts. Of the 724 participants, 36%
      reported that they had had sex while under the influence of alcohol. Of this
      group, 31% indicated that safer sex procedures were neglected owing to the
      influence of alcohol. No significant differences with regard to unprotected
      sexual intercourse were found between subjects who combine sex and alcohol and
      those who do not. The same was found to be true among subjects with different
      levels of general alcohol consumption. However, a significant correlation was
      found between the intensity of alcohol consumption (i.e., the quantity of alcohol
      intake per sitting) and the incidence of unprotected sexual intercourse. These
      findings show that the relationship between alcohol consumption and safer sex is
      complex; they also emphasize the need for preventive efforts to reinforce safer
      sexual behavior, for example through individual counseling of persons at risk for
      HIV-infection.

PMID- 8876848
TI  - Low antituberculosis drug concentrations in patients with AIDS.
AB  - OBJECTIVE: To determine the frequency and magnitude of below normal apparent peak
      serum concentrations for antituberculosis drugs in patients with AIDS and CD4
      cell counts less than 200 cells/mm3. We also explored the data for potential
      relationships between response variables and patient characteristics. DESIGN:
      Prospective study of consecutive patients seen in tuberculosis clinics. SETTING:
      Five urban tuberculosis clinics in four major metropolitan areas. PARTICIPANTS:
      Twenty-six patients diagnosed with HIV infection and receiving treatment for
      active tuberculosis were eligible. MAIN OUTCOME MEASURES: After 2 weeks or more
      of therapy, blood was collected 2 hours after observed doses of the
      antituberculosis drugs. Serum samples were frozen, shipped to National Jewish
      Center in Denver, and analyzed by HPLC or GC. Serum concentrations were compared
      with the proposed normal ranges. Data were analyzed to determine correlations
      between antituberculosis drug serum concentrations and patient characteristics.
      RESULTS: Low-2-hour serum concentrations were common for antituberculosis drugs,
      particularly rifampin and ethambutol. Absorption of isoniazid was generally high.
      Potential drug-drug interactions were found between rifampin and fluconazole
      (fluconazole appears to increase rifampin concentrations) and between
      pyrazinamide and zidovudine (zidovudine may lower pyrazinamide concentrations).
      Patients receiving pyrazinamide had lower rifampin concentrations than those not
      receiving pyrazinamide. CONCLUSIONS: Low antituberculosis drug serum
      concentrations occur frequently during the treatment of tuberculosis in patients
      with AIDS. Additional research is required for patients with drug-resistant
      tuberculosis, and to clarify the nature of the potential drug-drug interactions.

PMID- 8876849
TI  - Quantifying the clinical significance of drug-drug interactions: scaling
      pharmacists' perceptions of a common interaction classification scheme.
AB  - OBJECTIVE: To develop a precise, interval level scale of the clinical
      significance of drug-drug interactions that reflects the professional judgments
      of practicing pharmacists. PARTICIPANTS: A convenience sample of 63 practicing
      pharmacists representing hospital (clinical and staff) and retail (chain and
      independent) practice settings. METHOD: Pharmacists judged the similarity among
      15 interaction categories that have been commonly used to classify drug-drug
      interactions. A multidimensional scaling technique produced a spatial
      representation (i.e., a psychological map) of the structure inherent in those
      similarity judgments. Pharmacists' ratings of clinical significance were
      projected onto that same spatial representation using a multiple regression
      procedure, and the resulting information was used to develop a scale of clinical
      significance. RESULTS: The clinical significance scale developed from
      pharmacists' judgments was substantially different from a comparison scale
      published in a popular reference. The new scale was more precise than the
      comparison scale, and it also approximated an interval level of measurement. The
      judgments used to produce the new clinical significance scale were not reliably
      influenced by pertinent demographic characteristics of the sample. CONCLUSIONS:
      Inconsistencies between published clinical significance scales and the
      professional judgments of practitioners could affect patient care to the degree
      that a summary measure of clinical significance affects a practitioner's response
      to a potential drug-drug interaction. The clinical significance scale developed
      in this study has good measurement characteristics and reflects the professional
      judgments of practicing pharmacists. Use of the new scale is recommended on these
      grounds, although further assessment of its generality is warranted.

PMID- 8876850
TI  - Serum concentrations of salicylic acid following topically applied salicylate
      derivatives.
AB  - OBJECTIVE: To compare the rate and extent of systemic salicylate absorption
      following single and multiple applications of two topically applied analgesics,
      one containing methyl salicylate and the other containing trolamine salicylate.
      DESIGN: Two-period, two-treatment, randomized, crossover, multiple-dose study in
      healthy men and women volunteers. PARTICIPANTS: Six men and six women volunteers,
      21-44 years of age. INTERVENTIONS: Subjects applied 5 g of an ointment containing
      12.5% methyl salicylate twice daily for 4 days (8 doses) or a cream containing
      trolamine 10% twice daily for two doses, to a 10-cm2 area on the thigh. Treatment
      order and leg (right or left) were assigned randomly. Subjects were crossed over
      to the alternate treatment on the other leg after a minimum washout period of 7
      days. MAIN OUTCOME MEASURES: The total amount of salicylate recovered in the
      urine during two dosing intervals (24 hours) on each study day, relative to the
      applied dose, was used to calculate the bioavailability of each product. Mean
      standard pharmacokinetic parameters including area under the curve, maximum
      concentration (Cmax), time to maximum concentration, and minimum concentrations
      at steady-state were determined from serum concentrations. Serum concentrations
      were fit to three pharmacokinetic models and the suitability of each model was
      evaluated. Estimates of absorption rate constant, clearance, volume, and fraction
      absorbed on day 1 were estimated by using the best-fitting model. RESULTS:
      Salicylic acid could not be detected in serum after trolamine application.
      However, concentrations between 0.31 and 0.91 mg/L were detected within 1 hour of
      the first application of methyl salicylate and Cmax between 2 and 6 mg/L were
      observed following the seventh application on day 4. Both the extent and rate of
      absorption changed after the first 24 hours. The absorption rate constant
      increased significantly from the first to the seventh dose (first dose absorption
      rate constant: 0.16 h-1, seventh dose: 0.28 h-1; p < 0.035). Urinary recovery of
      total salicylate (salicylic acid and principal metabolites of salicylic acid)
      during the first 24 hours of the methyl salicylate phase averaged 175.2 mg,
      exceeding the 6.9 mg (p < 0.05) recovered during the trolamine phase. The
      recovery of salicylate in the urine in the first 24 hours after application of
      methyl salicylate was significantly greater than the 1.4% recovered after
      application of trolamine (p < 0.05). Furthermore, the fraction of methyl
      salicylate recovered in the urine increased significantly from 15.5% on day 1 to
      approximately 22% on the second, third, and fourth days. CONCLUSIONS: A
      considerable amount of salicylic acid may be absorbed through the skin after
      topical application of methyl salicylate products and this may increase with
      multiple applications. Caution is warranted in patients for whom systemic
      salicylate may be hazardous or problematic.

PMID- 8876851
TI  - Evaluation of symptom distress in a bone marrow transplant outpatient
      environment.
AB  - OBJECTIVE: To measure patient perceptions of autologous bone marrow
      transplantation (ABMT)-associated symptoms in the outpatient setting, assess the
      efficacy of the established antiemetic protocol, evaluate patient satisfaction,
      and report patient medication compliance. DESIGN: A prospective, descriptive
      study of patients with breast cancer who were enrolled in an outpatient ABMT
      program. SETTING: Duke University Autologous Bone Marrow Transplantation Program.
      METHODS: Patient perceptions of 12 symptoms were measured by the Symptom Distress
      Scale (SDS) on the day of admission to the hospital, the day of discharge to the
      outpatient clinic, after bone marrow reinfusion, and before patient release from
      the clinic. The number of retching and vomiting episodes was recorded by each
      patient daily. Patient satisfaction was determined by a standardized personal
      interview conducted prior to discharge. Patient compliance was assessed by a
      review of patient medication documentation. RESULTS: Twenty-eight patients were
      enrolled over 5 months. The median SDS scores for each symptom evaluated revealed
      that anorexia, nausea, fatigue, insomnia, and bowel problems were the most
      distressing symptoms patients experienced in the outpatient ABMT program. Scores
      for pain, negative outlook, cough, diminished concentration, and change in
      appearance indicated only mild distress associated with these variables. The
      total number of vomiting episodes ranged from 1 to 33 total episodes per patient
      per outpatient stay. The percentage of patients experiencing a complete
      antiemetic response ranged from 24% to 48% over the 4 days after chemotherapy but
      steadily improved thereafter to a peak of 90% 1 week later. Patient satisfaction
      results showed that patients preferred being out of the hospital and reported
      their anxiety controlled although most had some problems with the outpatient
      clinic or medications required. CONCLUSIONS: Loss of appetite, fatigue, and
      insomnia have been identified as symptoms that are frequently present during the
      course of the outpatient ABMT program. Mild, intermittent nausea persists in the
      outpatient setting for up to 9 days after bone marrow transplant despite
      continuous combination antiemetic therapy. Patient interviews confirmed the
      belief that patients enjoy being out of the hospital. Medication compliance is
      more than 90% in this structured outpatient setting.

PMID- 8876852
TI  - Polypharmacy among nursing home geriatric Medicaid recipients.
AB  - OBJECTIVE: To determine the factors that influence the number of different drugs
      prescribed to geriatric Medicaid recipients residing in Louisiana's intermediate
      care facilities I (ICFs I). DESIGN: Observational and cross-sectional with
      descriptive and analytic components. PARTICIPANTS: All geriatric Medicaid
      recipients in Louisiana ICFs I during 1994 (n = 19932). METHODS: Relevant data on
      sex, age, race, geographic region of a recipient, number of prescribing
      physicians, number of pharmacies used, and the number of drugs prescribed to a
      recipient were extracted from the state Medicaid files. Frequencies for the seven
      study variables were calculated. Regression analysis was used to evaluate the
      influence of the six predictor variables on the number of drugs prescribed.
      RESULTS: The study population was 73.63% women, 60.07% 81 years of age and older,
      70.65% white, 23.21% African-American, 6.14% other races, and 29.83% from
      predominantly rural north Louisiana. A total of 44.60% of the residents received
      prescriptions from one physician, 8.41% of the residents were single pharmacy
      users, and 45.65% were prescribed more than 10 drugs during the year. The
      regression model accounted for 20.53% of the total variation in the number of
      drugs prescribed to a recipient. Race, geographic region, number of prescribing
      physicians, and number of pharmacies used by a recipient influenced the number of
      drugs prescribed. CONCLUSIONS: To reduce the number of drugs prescribed and
      polypharmacy among geriatric Medicaid recipients, Louisiana's ICFs I should
      minimize the number of physicians and pharmacies used in this population.

PMID- 8876853
TI  - Azathioprine and allopurinol: the price of an avoidable drug interaction.
AB  - OBJECTIVE: To report the price of a drug interaction between azathioprine and
      allopurinol that resulted in pancytopenia in a patient who had undergone a heart
      transplant. CASE SUMMARY: A 63-year-old white man who received an orthotopic
      heart transplant in 1987 was hospitalized in June 1991 with a diagnosis of
      pancytopenia. His immunosuppressive medications on admission included
      cyclosporine 125 mg bid, azathioprine (AZA) 200 mg/d, and prednisone 2.5 mg/5 mg
      every other day. Six weeks prior to admission, the patient's local physician
      prescribed allopurinol for left wrist pain suspected to be gout. It was
      determined that the pancytopenia was caused by the drug interaction between AZA
      and allopurinol, both of which were withheld on admission. During
      hospitalization, the patient's white blood cell count dropped to 1.1 x 10(3)/mm3
      with an absolute neutrophil count of less than 0.5 x 10(3)/mm3, a platelet count
      of less than 20 x 10(3)/mm3, and a hemoglobin of 3.7 g/dL. Four units of packed
      red blood cells were transfused and regramostim (GM-CSF) therapy was begun on
      hospital day 3 to speed the marrow recovery process. The patient was discharged
      on hospital day 8 and AZA, which had been withheld since admission, was
      restarted. The dosage was titrated to 200 mg/d over the following 2 weeks. The
      price of this patient's hospital stay was $13,042. DISCUSSION: Not included in
      this price was the effect this drug interaction had on the patient's quality of
      life. Even after discharge from the hospital, it was estimated that it would take
      up to 3 months for the patient to fully recover his previous level of strength
      and functional capability. This interaction between AZA and allopurinol could
      easily have been avoided. Both the physician and the pharmacist missed this well
      documented and potentially life-threatening drug interaction. Also, the patient
      failed to notify the transplant team when allopurinol was prescribed by his local
      physician. The importance of patient responsibility for medication therapy must
      be stressed to help avoid unnecessary drug interactions. CONCLUSIONS: Undetected
      drug interactions can be life-threatening to patients as well as costly to the
      healthcare system. Drug interactions also can have a profound negative effect on
      the patients' quality of life, the price of which cannot be measured in dollars
      alone. It is vital that the physician, pharmacist, and patient work together to
      optimize therapeutic outcomes and avoid unnecessary drug interactions.

PMID- 8876854
TI  - Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant.
AB  - OBJECTIVE: To describe a novel treatment for perianal excoriation in an infant
      receiving a promotility agent. CASE SUMMARY: A 2-month-old boy with reflux, and
      regurgitation was treated with cisapride. Shortly after cisapride therapy he
      developed a rash on his buttocks and anal irritation that progressed in severity
      despite the use of numerous topical products and extended diaper-free periods. A
      topical cholestyramine ointment compound was prepared and administered, resulting
      in complete resolution within 3 days. DISCUSSION: Cisapride can decrease the
      gastrointestinal transit time, which can lead to less time for bile acid
      reabsorption in the distal ileum. If high concentrations of bile acids are
      contained in the stool, they can irritate the anus and buttocks in a manner
      similar to the skin irritation experienced by patients with ostomies.
      Cholestyramine, a bile acid sequestrant, can irreversibly bind the bile when
      applied topically and bring relief to the patient. CONCLUSIONS: Topical
      cholestyramine ointment may be a safe and efficacious treatment option for
      perianal irritation due to bile acids.

PMID- 8876855
TI  - Acute dystonic reaction to methotrimeprazine in hypoparathyroidism.
AB  - OBJECTIVE: To report a case of acute dystonic reaction to methotrimeprazine in a
      patient with untreated hypoparathyroidism, emphasizing the potential increased
      sensitivity of hypocalcemic patients to the extrapyramidal adverse effects of
      antipsychotic drugs. CASE SUMMARY: An 80-year-old man who had untreated
      hypoparathyroidism and chronic hypocalcemia developed an acute dystonic reaction
      20 minutes after ingestion of methotrimeprazine 25 mg. His medical history
      included an ill-defined psychiatric disorder for which he had been treated with
      methotrimeprazine several years earlier. The patient denied having any other
      diseases or taking any other medications. After 4 days, the disorientation,
      psychomotor restlessness, dystonic grimacing, protrusion of the tongue, and
      speech difficulties disappeared, despite a remaining low serum calcium
      concentration. DISCUSSION: A possible mechanism, by which striatal calmodulin
      mediated adenylate cyclase activation is inhibited by the combined effects of
      phenothiazines and hypocalcemia, is discussed. CONCLUSIONS: In this patient, it
      is not possible to ascertain whether the dystonic reaction was due to
      hypocalcemia, phenothiazine administration, or both. However, it is suggested
      that patients with hypocalcemia may be sensitive to the extrapyramidal adverse
      effects of antipsychotics. In addition, acute unexpected dystonic reactions to a
      small dose of antipsychotics warrants measurement of the patient's serum calcium
      concentration.

PMID- 8876856
TI  - Propylthiouracil-induced hepatic damage.
AB  - OBJECTIVE: To report a case of propylthiouracil-induced hepatic damage. CASE
      SUMMARY: A 64-year-old white woman with hyperthyroidism received propylthiouracil
      250 mg/d for 1 year. She developed hepatitis after 1 year of therapy. Alcohol and
      drug abuse were ruled out and all serologic tests for hepatitis A, B, and C were
      negative. Cytomegalovirus and Epstein-Barr virus infection were also ruled out.
      Antinuclear antibody, antimitochondrial antibody, and antismooth muscle antibody
      were negative. The clinical picture was similar to that of viral hepatitis
      characterized by nausea, vomiting, and jaundice. Histologic examination of a
      liver biopsy specimen showed chronic active hepatitis. The patient developed
      cirrhosis during follow-up. DISCUSSION: Propylthiouracil is widely used in the
      treatment of hyperthyroidism. Despite its widespread use, there have been only a
      few reported cases of propylthiouracil-induced hepatotoxicity. The precise
      mechanism of the injury is unknown, although immunologic factors are suggested.
      CONCLUSIONS: Hepatic damage induced by propylthiouracil is a rare complication.
      However, the danger of permanent hepatic damage should be kept in mind. The best
      way of preventing propylthiouracil hepatotoxicity is careful screening of
      patients considered for treatment.

PMID- 8876857
TI  - Antiviral drug development: the road less taken.

PMID- 8876858
TI  - The past as prelude to the future: history, status, and future of antiviral
      drugs.
AB  - OBJECTIVE: To review the first generation of antiviral agents (e.g., idoxuridine,
      amantadine, vidarabine) that paralleled discovery of antineoplastic agents. DATA
      SOURCES: A MEDLINE search (1962 to 1996) of the English-language literature
      pertaining to antiviral agents was performed. DATA EXTRACTION: All articles were
      considered for this review. Pertinent references on antiviral therapy, as judged
      by the author, were selected. DATA SYNTHESIS: Acyclovir, the first second
      generation antiviral agent, has a known selective mechanism of action and
      provides the model for development of future antiviral therapies. Despite the
      safety and clinical value of acyclovir, therapy does not prevent establishment of
      latency or decrease frequency of occurrences, resistance has been documented, and
      outcome is frequently poor. With the emergence of the HIV/AIDS epidemic, several
      antiretroviral agents have been developed and approved. However, none of the four
      available nucleoside analogs provides a cure. CONCLUSIONS: Viral resistance has
      emerged as an important component of antiviral therapy. Improved therapies for
      cytomegalovirus are needed. Several new therapies for herpes zoster, including
      prodrugs, are licensed or in Phase III clinical trials. Future directions include
      the use of molecular biologic techniques to identify enzymes unique to viral
      replication and to accelerate diagnosis of viral diseases.

PMID- 8876859
TI  - Pharmacologic considerations for antiviral drug development.
AB  - OBJECTIVE: To discuss pharmacologic considerations for the development of
      antiviral agents. DATA SOURCES: English-language literature pertaining to the
      development and clinical evaluation of antiviral compounds, primarily agents
      targeted against herpes group viruses and HIV. STUDY SELECTION AND DATA
      EXTRACTION: Pertinent information, as judged by the author, was selected for
      discussion. DATA SYNTHESIS: Drug development of antiviral agents presents unique
      problems compared with that of antimicrobial and other agents. Understanding the
      mechanism of action and both pharmacokinetic and pharmacodynamic considerations
      is critical to developing a rational dosing strategy and safe, effective use. The
      lack of standardized methods for antiviral susceptibility testing and the
      influence of factors such as strain of virus, host cell type, culture medium,
      inoculum size, end point, and method of measurement on the results obtained
      illustrate factors that complicate preclinical pharmacologic analysis of
      antiviral agents. Acyclovir offers a model for clinical drug development. Its
      mechanism of action, pharmacokinetics, and pharmacodynamics have been studied
      extensively. Rational guidelines for usage are available, including guidelines in
      special patient populations such as kidney transplant recipients and neonates. A
      pregnancy registry has allowed evaluation of the incidence of birth defects in
      fetuses exposed to systemic acyclovir. Several pitfalls in antiviral drug
      development are associated with inadequate pharmacologic information. The
      development of dextran sulfate and fialuridine provides two examples. Integration
      of pharmacokinetic and pharmacodynamic analyses using modern sampling and
      analysis techniques may facilitate more rapid development of antiviral agents and
      more informed dosage regimens to achieve the highest probability of therapeutic
      success.

PMID- 8876860
TI  - Famciclovir for treatment of herpesvirus infections.
AB  - OBJECTIVE: To discuss the antiviral activity, pharmacokinetics, clinical
      efficacy, and adverse effect profile of famciclovir, the oral prodrug of
      penciclovir (PCV), and to compare these features of famciclovir with those of
      acyclovir in the treatment of herpesvirus infections. DATA SOURCES: Literature
      was identified by MEDLINE search, and abstracts from recent meetings were
      included where relevant. Data provided by the manufacturer were also used. STUDY
      SELECTION: Data regarding antiviral activity were included if accepted and widely
      used methods were followed. Clinical trials in which a comparison with acyclovir
      or placebo was performed were given the highest priority. DATA SYNTHESIS: In
      comparison with acyclovir, PCV has similar antiviral activity although its mode
      of action is not identical. When administered orally, faMciclovir, the oral
      prodrug of PCV, is better absorbed than acyclovir, yielding an absolute
      bioavailability of PCV of 77%. The predominant route of PCV elimination is via
      the kidneys, with a half-life of approximately 2.5 hours. In trials comparing
      famciclovir with acyclovir for the treatment of herpes zoster in immunocompetent
      individuals, comparable results were obtained. Famciclovir is also effective as
      therapy for recurrent episodes of genital herpes and may prove useful for chronic
      suppressive therapy. The most common adverse effects of famciclovir are headache
      and gastrointestinal upset. The dosage of famciclovir for herpes zoster in
      immunocompetent individuals is 500 mg po tid for 7 days; for recurrent genital
      herpes a dosage of 125 mg po bid for 5 days is recommended. Dosage adjustments
      are necessary in patients with renal dysfunction. CONCLUSIONS: Given its
      comparable efficacy, similar adverse effect profile, and less frequent dosing
      schedule than acyclovir, famciclovir represents a viable alternative for
      treatment of herpes zoster and for episodic therapy of recurrent genital herpes
      in immunocompetent adults. Specific recommendations for other uses of famciclovir
      await the publication of recent clinical trial results.

PMID- 8876861
TI  - What is the role of angiotensin-converting enzyme inhibitors in congestive heart
      failure and after myocardial infarction?
AB  - OBJECTIVE: To discuss the controversies surrounding the choice of angiotensin
      converting enzyme (ACE) inhibitor, and the timing, dosage, and duration of ACE
      inhibitor therapy for congestive heart failure (CHF) and after myocardial
      infarction (MI). The beneficial effects of ACE inhibition in patients with CHF
      and after MI are reviewed. Human clinical trials are reviewed and their clinical
      implications are discussed. DATA SOURCES: MEDLINE searches (1985-1995) identified
      human clinical trials and review articles. DATA EXTRACTION: Landmark human
      clinical trials with morbidity and mortality end points were included. The
      validity of the study data were assessed on the basis of study methods,
      population characteristics, and statistical power. DATA SYNTHESIS: ACE inhibitors
      exert beneficial effects in patients with CHF by hemodynamic and neurohormonal
      mechanisms. The attenuation of ventricular remodeling that occurs with ACE
      inhibition does not fully explain the results of clinical trials in patients
      after MI. Routine determination of ejection fraction to guide ACE inhibitor
      therapy is not as important as the patient's clinical status. Clinicians should
      titrate the chosen ACE inhibitor on the basis of hemodynamic response to target
      doses used in major clinical trials. Because the beneficial effects of ACE
      inhibitors appear to be a class effect, choice of an agent should include cost
      considerations and the results of clinical trials. CONCLUSIONS: ACE inhibitor
      reduce morbidity and mortality in selected CHF and post-MI patients. Patients
      with symptomatic CHF benefit most from ACE inhibitor therapy, and it should be
      continued indefinitely. Treatment effects in asymptomatic patients are delayed.
      The role of ACE inhibitor therapy in preventing morbidity and morality in
      asymptomatic patients with preserved ventricular function requires further study.

PMID- 8876862
TI  - Syncope: pathophysiology, diagnosis, and pharmacotherapy.
AB  - OBJECTIVE: To review the pathophysiology, diagnosis, and pharmacotherapy of
      syncope, with emphasis placed on neurocardiogenic syncope. DATA SOURCES: A
      MEDLINE search (1980-1995) using the term syncope and cross-referencing selected
      articles. STUDY SELECTION: Articles selected were those considered to assist in
      providing the reader with a basic introduction the pathophysiology, diagnosis,
      and pharmacotherapy of syncope, with emphasis placed on neurocardiogenic syncope.
      DATA SYNTHESIS: Syncope is a common disorder with many different etiologies. The
      patient's history and physical examination are extremely important in making the
      diagnosis. The recent availability of head-upright tilt testing and
      electrophysiologic studies of the myocardium have helped define the etiology in
      many patients in whom an etiology would not have been found in the past. When the
      cause of syncope has been diagnosed, the appropriate therapy to prevent future
      attacks will be defined in many instances. One form of syncope, known as
      neurocardiogenic syncope, can be difficult to treat. Recent trials have suggests
      the use of beta-blockers, fludrocortisone, disopyramide, or selective serotonin
      reuptake inhibitors may be helpful in some patients.

PMID- 8876863
TI  - Nefazodone: its place among antidepressants.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, adverse
      effects, and drug interactions of nefazodone as well as to determine its place
      among currently available antidepressants. DATA SOURCES: A search of European and
      American literature using EMBASE and MEDLINE was completed. Nefazodone was the
      search term. DATA SYNTHESIS: Nefazodone is an antidepressant that blocks
      serotonin type 2 (5-HT2) receptors in addition to inhibiting the reuptake of
      serotonin and norepinephrine. In double-blind, placebo-controlled studies,
      nefazodone demonstrates antidepressant activity at dosages ranging from 400 to
      600 mg/d. Sedation, dry mouth, nausea, and dizziness are the more common adverse
      effects of nefazodone. Nefazodone, an analog of trazodone, has not been
      associated with priapism at this time, and may have fewer sexual adverse effects
      than other antidepressants. More studies are needed to determine the potential
      role of nefazodone in treating anxiety, pain, and premenstrual syndrome. STUDY
      SELECTION: Only double-blind, placebo-controlled studies designed to establish
      the efficacy of nefazodone as an antidepressant were reviewed. CONCLUSIONS: Based
      on placebo-controlled, double-blind, comparative trials, nefazodone demonstrates
      greater efficacy than placebo, and equivalent efficacy to imipramine. Somnolence,
      dry mouth, nausea, dizziness, and constipation are the most common adverse
      effects. Nefazodone appears to have a milder adverse effect profile than the
      tricyclic antidepressants, causes fewer sexual dysfunctions than the serotonin
      selective reuptake inhibitors, and may cause less dizziness than trazodone.
      Nefazodone at dosages of at least 300 mg/d provides another option for the
      treatment of depression.

PMID- 8876864
TI  - Placebo response in anxiety disorders.
AB  - OBJECTIVE: To review literature on placebo response in anxiety, to discuss
      sources and levels of placebo response in various anxiety disorders, and to
      suggest methods to prevent high placebo response rates in clinical research
      trials. DATA SOURCE: Data from scientific literature were identified using a
      MEDLINE search, and were extracted and summarized for this review. STUDY
      SELECTION: Representative findings were selected from clinical and epidemiologic
      studies, review articles, letters to the editor, book chapters, and proceedings.
      DATA EXTRACTION: Data from English-language reports of studies on humans were
      included. Only the most representative conclusions drawn from review articles
      were used. DATA SYNTHESIS: Anxiety disorders in general are thought to be
      extremely susceptible to a variety of influences, including patient
      characteristics and environmental variables. Reported placebo response levels in
      clinical studies of anxiolytics for generalized anxiety disorder and panic
      disorder vary widely, with a tendency to be rather high, although studies in
      social phobia and obsessive compulsive disorder appear to have consistently low
      placebo response rates. Comparisons of anxiety studies with studies of other
      indications, such as depression, show similar overall placebo response rates. To
      determine efficacy, drug response rates and placebo response rates must be
      clearly differentiated. CONCLUSIONS: Examination of the literature suggests that
      placebo response rates in studies of anxiolytics are influences by a number of
      factors, including both endogenous and exogenous variables. High placebo response
      rates may mask true drug response rates and may result from poor study design or
      lack of procedural standardization. The use of certain design methods may help to
      prevent high placebo response rates in anxiolytic clinical trials.

PMID- 8876865
TI  - Quinolones for the treatment and prophylaxis of tuberculosis.
AB  - Quinolones possess enormous potential as antimycobacterial agents, and have been
      proven to have excellent in vitro activity against M. tuberculosis, as well as
      limited in vivo efficacy. These drugs appear to be safe and well tolerated even
      when taken for an extended period. This is important considering that one of the
      most significant factors contributing to resistance is compliance. Quinolones
      exhibit great promise for initial treatment and retreatment of MDRTB, a rapidly
      growing problem, as well as for prevention. They have shown to be as effective as
      some of the first-line agents currently used in treating TB. There appears to be
      overwhelming need to further study these agents and determine their role in the
      treatment of TB. In the future, quinolones may emerge as first-line therapy for
      TB.

PMID- 8876866
TI  - Nicotine therapy for ulcerative colitis.
AB  - Smoking has been associated with a decreased frequency of UC. Currently, the role
      of nicotine for the treatment of UC is not established. Several studies have
      evaluated nicotine gum and transdermal patches as supplemental therapy for stable
      UC, but nicotine has not been compared with other treatment modalities. Nicotine
      dosages in the studies have varied from 5 to 30 mg/d without apparent dose
      related therapeutic effects, and many patients have found relief from placebo
      treatment. Patients often do not tolerate nicotine therapy's adverse effects,
      which can include nausea, light-headedness, and headache. Due to the cyclic
      disease course of UC and the potential addictiveness of nicotine, further large
      studies are warranted to assess the benefits of nicotine therapy for UC. These
      studies should be conducted using a randomized, double-blind design with an
      extensive follow-up period. Until further trials are conducted, nicotine should
      generally not be recommended for UC treatment.

PMID- 8876867
TI  - AUIC--a general target for the optimization of dosing regimens of antibiotics?
AB  - OBJECTIVE: To present a systematic evaluation of the are under the inhibitory
      curve (AUIC) approach for the optimization of antibiotic dosing schedules for
      three major antibiotic classes (beta-lactams, quinolones, aminoglycosides). It
      has been proposed that an AUIC over 24 hours of at least 125 may be an applicable
      target parameter for the optimization of antibiotic dosing schedules across these
      antibiotic classes. Some limitations of this approach are presented and
      discussed. METHODS: A precise equation for the calculation of AUIC is derived.
      Moreover, a specific equation is derived for the situation that results in a
      trough concentration at the end of the dosing interval equal to the minimum
      inhibitory concentration (MIC). With the same three drugs used for deriving the
      target AUIC value (tobramycin, cefmenoxime, ciprofloxacin), different dosing
      regimens are simulated to obtain the target AUIC of 125. RESULTS: Very different
      serum concentration profiles can result in the same AUIC. In an example for
      cefmenoxime, dosing regimens of 1 g q6h and 4.2 g q24h resulted in equal AUIC
      values of 125, whereas the respective time above MIC differed dramatically (99%
      of the dosing interval for q6h vs. 36% for q24h). CONCLUSIONS: It does not seem
      valid to accept the proposed breakpoint AUIC target of at least 125 as an
      applicable value for determining the appropriate dosing schedule of these classes
      of antibiotics. Based on the limitations discussed about the AUIC approach, the
      same conclusion also holds for any other fixed AUIC breakpoint target value.

PMID- 8876868
TI  - AUIC--the universal parameter within the constraint of a reasonable dosing
      interval.

PMID- 8876869
TI  - New regulations for pediatric labeling of prescription drugs.

PMID- 8876870
TI  - Quinolones and tuberculosis.

PMID- 8876871
TI  - Acute renal failure with amphotericin B in lipid emulsion.

PMID- 8876872
TI  - Anaphylactic reaction to liposomal amphotericin B in children.

PMID- 8876873
TI  - Precipitation of lorazepam infusion.

PMID- 8876874
TI  - Vancomycin removal by plasmapheresis.

PMID- 8876875
TI  - Hepatitis A, B, C, D, and E: making sense of the alphabet soup.

PMID- 8876876
TI  - Monitoring the safety of Chinese herbal medicines in Hong Kong.

PMID- 8876877
TI  - Drug package inserts in India.

PMID- 8876878
TI  - Diflunisal cross-reactivity with the Trinder method for salicylate determination.

PMID- 8876879
TI  - Comment: opioid-induced muscle activity.

PMID- 8876880
TI  - Correction: chemical structures of serotonin and serotonin-receptor antagonists.

PMID- 8876881
TI  - Preoperative radiotherapy for rectal cancer: benefits and controversies.

PMID- 8876882
TI  - Postoperative radiotherapy for locally advanced colon cancer.

PMID- 8876883
TI  - Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm
      Colorectal Cancer Study Group.
AB  - BACKGROUND: A population based prospective randomized trial on preoperative
      radiotherapy in operable rectal cancer was conducted in Stockholm, Sweden. Five
      hundred fifty-seven patients from 12 institutions were included with
      histologically proven, clinically resectable rectal adenocarcinoma. Patients
      planned for local excision or previously irradiated to the pelvis were excluded.
      METHODS: A total of 272 patients were allocated to preoperative irradiation with
      25 Gy in five cycles during 5-7 days to the rectum and the pararectal tissues
      (RT+ group) and 285 patients were allocated to surgery only (RT- group). The
      median follow-up time was 50 months. No patient was lost to follow-up. Surgery
      was considered curative in 479 patients (86%). RESULTS: Locoregional recurrence
      occurred in 10% of the patients in the RT+ group versus 21% in the RT- group (p <
      0.01). Among the curatively operated patients, distant metastases occurred in 19%
      in the RT+ group versus 26% in the RT- group (p = 0.02). The overall survival was
      improved in the irradiated patients (p = 0.02). Postoperative complications were
      more common after irradiation but were usually mild. The postoperative mortality
      was low in both groups. CONCLUSION: Preoperative short-term, high-dose
      radiotherapy as given in this trial reduces the risk of local and distant
      recurrence and improves survival after curative surgery for rectal carcinoma.

PMID- 8876884
TI  - Postoperative radiotherapy for locally advanced colon cancer.
AB  - BACKGROUND: The role of adjuvant postoperative radiotherapy for locally advanced
      colon cancer is not well documented. METHODS: Seventy-eight patients who
      underwent a complete resection of B2-C colon cancer received postoperative
      radiotherapy. Twenty-eight patients received < or = 45 Gy; 50 patients received
      50-55 Gy. Twenty-seven patients received adjuvant fluorouracil-based
      chemotherapy. All patients were followed for a minimum of 3 years; no patients
      were lost to follow-up. RESULTS: The overall local control rate was 88%. The 5
      year actuarial rate of local control was 96% after 50-55 Gy postoperative
      radiotherapy compared with 76% after < 50 Gy (p = 0.0095). Multivariate analysis
      of local control showed that only radiotherapy dose significantly influenced this
      end point. Cause-specific survival rates at 5 years were B2, 67%; B3, 90%; C1,
      100%; C2, 61%; C3, 36%; and overall, 63%. Multivariate analysis of cause-specific
      survival showed that only stage significantly influenced this end point. Bowel
      obstruction caused by adhesions developed in three patients and required a
      laparotomy; radiation-induced sarcoma developed in one additional patient.
      CONCLUSIONS: Postoperative radiotherapy appears to reduce the risk of local
      recurrence in patients with locally advanced colon cancer. The optimal dose is
      probably 50-55 Gy at 1.8 Gy per fraction. Postoperative radiotherapy may improve
      cause-specific survival for patients with stages B3 and C2 cancers.

PMID- 8876885
TI  - Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma:
      an immunologic survival model.
AB  - BACKGROUND: Our polyvalent, allogeneic melanoma cell vaccine (MCV) induces
      immunoglobulin M (IgM) and immunoglobulin G (IgG) class antibodies to a 90-kDa
      glycoprotein melanoma-associated antigen (MAA). Additionally, MCV induces delayed
      type hypersensitivity (DTH) responses that we previously correlated with
      survival. We hypothesized that early DTH responses to MCV and early humoral
      responses to the 90-kDa MAA expressed on MCV cells may be predictive of overall
      survival. We tested this hypothesis by monitoring immunologic profiles in 59
      patients with melanoma who were receiving MCV after surgical resection of
      regional lymph node or soft-tissue metastases. METHODS: Blood was drawn before
      vaccine administration, biweekly for 6 weeks, and then monthly. DTH to MCV was
      recorded at 0, 2, 4, and 8 weeks of MCV therapy. Mean antibody titers during the
      first 6-week interval were calculated. Changes in DTH were calculated as the
      difference between peak and prevaccine values (delta DTH). RESULTS: At a median
      follow-up of 75.6 months (range 5-138), univariate analysis assigned prognostic
      significance to gender (p = 0.046), lymph node involvement (p = 0.024), delta DTH
      (p = 0.044), mean anti-90-kDa MAA IgG (p = 0.0009), and mean anti-90-kDa MAA IgM
      (p = 0.0014). In multifactorial analysis, only the three immunologic variables
      significantly impacted survival (p = 0.046, 0.0005, and 0.0053, respectively). A
      mathematical model based on delta DTH and mean anti-90-kDa MAA IgG and IgM titers
      closely approximated the observed individual and overall survival rates.
      CONCLUSIONS: The correlation between overall survival and initial
      humoral/cellular immune responses to MCV immunotherapy may be useful in selecting
      patients most likely to benefit from prolonged adjuvant immunotherapy.

PMID- 8876886
TI  - Local recurrence in malignant melanoma: long-term results of the
      multiinstitutional randomized surgical trial.
AB  - BACKGROUND: In the past, radical margins of excision were prescribed for
      cutaneous melanoma based on preconceived notions rather than on hard clinical
      evidence. METHODS: In a prospective study of 742 patients with intermediate
      thickness melanoma (1-4 mm), 470 patients with trunk or proximal extremity
      lesions were randomized into a 2- or 4-cm margin. Patients with distal extremity
      or head and neck lesions (n = 272) received uniformly a 2-cm margin. RESULTS: The
      overall rate of local recurrence was 3.8%. This rate in the randomized portion (n
      = 470) was 2.1% for the 2-cm margin and 2.6% for the 4-cm margin (p = 0.72). A
      progressive increase in local recurrence rates was observed with thickness: 2.3%
      for lesions 1.0-2.0 mm, 4.2% for those 2.01-3.0 mm, and 11.7% for those 3.01-4.0
      mm thick (p = 0.001). Local recurrence occurred in 1.5% of those without
      ulceration and in 10.6% of those with ulceration of the primary lesion (p =
      0.001). The local recurrence rate was not significantly affected by the margin of
      resection even among the thicker or ulcerated lesions. It also was not affected
      significantly by the method of closure of the primary site or management of the
      regional nodes, or the age or gender of the patients. CONCLUSIONS: A 2-cm margin
      is as effective as a 4-cm margin in local control and survival of intermediate
      thickness melanomas. The local recurrence rate is significantly affected by the
      thickness of the primary lesion and the presence or not of ulceration.

PMID- 8876887
TI  - Colorectal carcinoma and brain metastasis: distribution, treatment, and survival.
AB  - BACKGROUND: Brain metastasis from colorectal cancer is rare. The present study
      reports the nature of this disease and analyzes factors correlated with survival
      in patients harboring such disease. PATIENTS AND METHODS: One hundred patients
      diagnosed between 1980 and 1994 with metastatic brain tumors secondary to
      colorectal adenocarcinoma were retrospectively reviewed. Of these patients, 36
      underwent surgery, 57 underwent radiotherapy alone, and the remaining seven
      received steroids. RESULTS: The most common primary sites were the sigmoid colon
      and rectum (65%). Brain metastases with concomitant liver and/or lung metastases
      were seen more frequently than brain metastases alone. The median interval
      between the diagnosis of primary cancer and the diagnosis of brain metastasis was
      26 months (95% confidence interval = 22-30). The median survival time after the
      diagnosis of brain metastasis was 1 month for patients who received only
      steroids, 3 months for those who received radiotherapy (p = 0.1), and 9 months
      for those who underwent surgery (p < 0.0001). The extent of noncerebral systemic
      disease was not correlated with survival (p > 0.05), but early onset of brain
      metastasis was significantly associated with poor prognosis (p = 0.04).
      CONCLUSION: Surgical removal of colorectal metastatic brain lesions results in
      significantly increased survival time, regardless of the status of the
      noncerebral systemic disease.

PMID- 8876888
TI  - Routine compared with nonscheduled follow-up of patients with "curative" surgery
      for colorectal cancer.
AB  - BACKGROUND: The main rationale for follow-up of colorectal cancer patients
      resected for "cure" is that early detection and treatment of recurrence and
      metachronous disease should result in improved survival. Our purpose was to
      assess in a prospective fashion the impact on survival of a follow-up program
      versus that of undergoing nonscheduled visits. METHODS: Within the 14-year period
      from 1975 through 1988, a prospective study was carried out on 800 patients with
      colorectal adenocarcinoma radically resected with no evidence of synchronous
      cancers of the colon and rectum or in other organs, of whom 322 patients were to
      attend a 5-year follow-up, and 478 patients were free to make nonscheduled visits
      on account of symptoms. RESULTS: Asymptomatic recurrence was found at follow-up
      in 92 (28%) of 322 patients, whereas 175 (36%) of 478 patients had a symptomatic
      recurrence detected at a nonscheduled visit. Diagnosis of resectable recurrence
      was established within a median time of 21.5 months. Surgical resection of
      recurrence was performed in 30 (32%) of 92 and in 13 (7%) of 175 patients (32 vs.
      7%; p < 0.001). Resection was curative in 13 (14%) of 92 and in two (1%) of 175.
      Five-year survival of resected recurrence was 10% in 30 of 92 patients and 0.8%
      in 13 of 175 (10 vs. 0.8%; p < 0.01). Two patients are alive with no evidence of
      disease or two (2%) of 92. Metachronous colorectal lesions were treated for cure
      in 63 (19.5%) of 322 patients. The effectiveness of scheduled follow-up was 4%
      (13 of 322 patients). CONCLUSIONS: These results underline the rationale for a
      follow-up program in early detection and surgical treatment of recurrent disease
      in patients operated on for colorectal cancer.

PMID- 8876889
TI  - Cost-effective analysis of surgical palliation versus endoscopic stenting in the
      management of unresectable pancreatic cancer.
AB  - BACKGROUND: Ductal carcinoma of the pancreas is unresectable for cure in the
      majority of patients. We reviewed our results and cost effectiveness of surgical
      and endoscopic biliary bypass for unresectable pancreatic cancer to evaluate the
      comparable outcomes. METHODS: Between 1990 and 1992, 136 patients were managed
      operatively or endoscopically for pancreatic carcinoma. Excluding potentially
      curative resections and patients without follow-up, 34 patients endoscopically
      stented and 32 patients surgically bypassed were evaluated. RESULTS: Mean patient
      age was older (72.1 vs. 69.3 years) but average performance status was comparable
      (0.8 vs. 0.9 Eastern Cooperative Oncology Group grading) in the medical treatment
      group. The initial hospital stay was significantly longer for surgical patients
      (mean 14 vs. 7 days, p < 0.001), with higher average charges ($18,325 vs.
      $9,663). Twelve stented patients required rehospitalization (average charge of
      $4,029), and eight surgical patients were readmitted (average charge of $6,776).
      An average of 1.7 stent changes (average charge $1,190) were required. Mean
      survival was longer for the stented group (9.7 vs. 7.3 months, p = 0.13).
      CONCLUSIONS: Endoscopic stenting for unresectable pancreatic cancer provides
      equivalent duration of survival at reduced cost and shorter hospital stay,
      although subsequent stent changes are necessary. When curative resection is not
      possible, endoscopic biliary drainage should be considered a good first choice
      for palliative management.

PMID- 8876890
TI  - Ultrasound-guided biopsy of nonpalpable breast masses by surgeons.
AB  - BACKGROUND: Recently, ultrasound (US)-guided needle biopsy has been proposed as
      an acceptable alternative to open biopsy in women with nonpalpable breast masses.
      This study evaluated the accuracy of US-guided needle biopsy of nonpalpable
      breast masses performed by surgeons at the time of the initial clinical
      examination. METHODS: Ultrasound-guided aspiration and/or core biopsy (US-GAB)
      was performed on 103 patients presenting with a nonpalpable, new, or increasing
      size mass detected on mammography. Study patients included those whose US was
      classified as: fibroadenoma (FA) (n = 26), complex cyst (n = 32), indeterminate
      (complex cyst versus solid; N = 24), or suspect (n = 21). RESULTS: Of the 32
      patients with diagnostic US of complex cyst, US-GAB confirmed 27 to be cysts.
      Twelve additional cysts were aspirated among the 24 indeterminate lesions.
      Sixteen FA were diagnosed on US-GAB; 11 of these underwent open biopsy and each
      was demonstrated to be a FA. Fibrocystic/benign-breast change (FBC) was diagnosed
      on 26 US-GAB; 15 of these underwent open biopsy, which demonstrated three FA and
      12 FBC. Nine atypical lesions were diagnosed on US-GAB; six FBC, one papilloma,
      one FA, and one cancer were demonstrated on open biopsy. Seven cancers were
      diagnosed on US-GAB and all were confirmed on open biopsy. There were six
      insufficient specimens from US-GAB; four of these underwent open biopsy, which
      demonstrated two FA and two FBC. CONCLUSION: Ultrasound-guided aspiration and/or
      core biopsy performed by surgeons in conjunction with the initial clinical
      examination can accurately diagnose nonpalpable, mammographically detected breast
      masses.

PMID- 8876891
TI  - Surgical biopsy findings in patients with atypical hyperplasia diagnosed by
      stereotaxic core needle biopsy.
AB  - PURPOSE: To correlate the stereotaxic core needle biopsy results with those of
      surgical biopsy in patients with atypical lobular or ductal hyperplasia (atypical
      hyperplasia) diagnosed at stereotaxic core needle biopsy (SCNB). METHODS: We
      retrospectively reviewed the mammograms and pathology reports of 358 consecutive
      SCNBs performed in 323 patients. The results of SCNBs of 22 lesions reported as
      atypical hyperplasia were correlated with histologic findings at surgical biopsy.
      RESULTS: A histologic diagnosis of atypical hyperplasia at SCNB was found to be a
      poor predictor of the final surgical results. In the 19 patients with 22 lesions,
      surgical biopsy and SCNB results were in disagreement in 16, partial agreement in
      two, and complete agreement in only four lesions. Furthermore, five cases of
      atypical hyperplasia were shown to have invasive carcinoma on open biopsy, and
      five had ductal carcinoma in situ in the surgical biopsy, none of which was
      present on SCNB. CONCLUSION: Given the frequent occurrence of malignancy in
      patients diagnosed with atypical hyperplasia by SCNB, it is recommended that all
      such patients undergo excisional biopsy.

PMID- 8876892
TI  - Laparoscopy: an important tool in the staging of malignant pleural mesothelioma.
AB  - BACKGROUND: The current standard for the noninvasive staging of patients with
      malignant pleural mesothelioma is computed tomography (CT). However, CT often
      cannot determine whether a tumor is unresectable because of direct extension
      through the diaphragm to the peritoneal cavity. The aim of this prospective study
      was to determine whether laparoscopy detected transdiaphragmatic tumor extension
      when CT findings were equivocal. METHODS: From June 1993 to July 1994, 12 of 36
      patients considered for possible thoracotomy and surgical resection had equivocal
      CT findings of diaphragmatic invasion. All underwent laparoscopy using a
      multiport technique with diaphragmatic and peritoneal biopsies. RESULTS: The mean
      operative time was 83 min. There were no perioperative complications. The median
      hospital stay was 1 day. Six patients had biopsy-proven transdiaphragmatic
      extension, or peritoneal studding of tumor. The other six patients subsequently
      underwent thoracotomy: three had a complete resection, and three had unresectable
      tumor due to chest wall (N = 2) or mediastinal (N = 1) invasion. In no case was
      transdiaphragmatic extension of a tumor seen. CONCLUSIONS: This preliminary
      experience demonstrates that laparoscopy is a safe and accurate method for
      detecting transdiaphragmatic tumor extension when CT fails to do so. Laparoscopy
      should be considered a standard part of prethoracotomy staging in this subset of
      patients.

PMID- 8876893
TI  - Results of a phase I trial of a recombinant vaccinia virus that expresses
      carcinoembryonic antigen in patients with advanced colorectal cancer.
AB  - BACKGROUND: The inadequacy of systemic treatments of advanced colorectal cancer
      has aroused interest in biologic therapy. Recent animal models have demonstrated
      the efficacy and safety of a recombinant vaccine that contains vaccinia and the
      gene for carcinoembryonic antigen (rV-CEA). METHODS: A phase I clinical trial of
      rV-CEA was conducted to assess vaccine toxicities, the maximum tolerated dosage,
      resulting immune activities, and tumour responses. A dose-escalation protocol was
      devised for three concentrations. Six patients per dosage were each to receive
      three vaccinations. RESULTS: Seventeen patients with advanced colorectal cancer
      received a total of 44 vaccinations. Mild local and systemic reactions-comparable
      to those seen with vaccinia alone-were observed and were typically associated
      with the first vaccination. No significant complications or deaths were caused by
      the rV-CEA. In particular, no autoimmune colitis developed, nor did leukopenia
      occur, despite some homology between CEA and leukocyte antigens. All three
      vaccine concentrations were equally well tolerated. Most patients demonstrated
      tumor progression by clinical and radiographic parameters and by CEA levels.
      Immune assays are pending. CONCLUSIONS: This phase I trial demonstrated the
      safety of rV-CEA in patients with advanced colorectal cancer. Future clinical
      studies are warranted and will likely be influenced by investigations of the
      immune responses to the vaccine.

PMID- 8876894
TI  - Increased L-arginine transport in a nitric oxide-producing metastatic colon
      cancer cell line.
AB  - BACKGROUND: Little is known about amino acid transport in human neoplastic cells.
      We previously characterized L-arginine transport in the primary human colon
      cancer cell line, SW480, and found it is principally mediated by the sodium
      independent system y+. In this study, we characterized L-arginine transport in
      the metastatic cell line, SW620, and compared it with that in the primary cell
      line, SW480. METHODS: Transport of 3H-L-arginine in cell monolayers was analyzed
      in the presence and absence of sodium. Kinetic studies were performed over a
      range of L-arginine concentrations to determine transporter affinity (Km) and
      maximal transport velocity (Vmax). Transport was further characterized through
      blockade with known amino acids. In addition, the effect of cell age (i.e., time
      in culture) on arginine transport was examined at 2 and 9 days after seeding.
      Cellular proliferation was assessed by using the colorimetric 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. RESULTS: L
      Arginine uptake was primarily sodium independent in the SW620 cell line. Kinetic
      and amino acid-inhibition studies revealed a single high-affinity, sodium
      independent L-arginine transporter (Vmax = 1286.3 +/- 158.3 pmol/mg protein/30 s;
      Km = 46.8 +/- 4.2 microM). Sodium-independent transport was blocked by system y+
      substrates L-homoarginine, L-ornithine and L-lysine. Sodium-dependent uptake
      occurs through a single transporter with system BO,+ characteristics (Km = 16.15
      +/- 2.1 microM; Vmax = 329.94 +/- 29.7 pmol/mg protein/30 s). Arginine transport
      increased with time in culture with day 2 cells transport velocity = 241.7 +/-
      33.6 pmol/mg protein/30s, whereas day 9 cells transport velocity = 377 +/- 15.4
      pmol/mg protein/30 s (p < 0.01). Cellular-proliferation studies revealed a
      doubling time of 3.2 days for SW620 and 5.4 days for SW480 (p < 0.05).
      CONCLUSIONS: L-Arginine transport in these neoplastic cell lines occurs primarily
      through sodium-independent, high-affinity system y+. Vmax was increased 180% in
      the metastatic variant (SW620), suggesting upregulation of the Y+ transporter.
      The increased Y+ activity may be a mechanism to provide continuous substrate for
      tumor growth.

PMID- 8876895
TI  - Radiation oncology: of men and machines.

PMID- 8876896
TI  - Measuring quality of life in different cultures: translation of the Functional
      Living Index for Cancer (FLIC) into Chinese and Malay in Singapore.
AB  - Quality-of-life assessment has become an accepted method of evaluation in
      clinical medicine. The technique is based on a patient's self-assessment of
      physical, psychological, and social function, as well as the effects of
      distressing physical symptoms. The most important aspect of quality-of-life
      assessment is that it brings into focus a patient-centred view of health outcome,
      which is broader than the physiologic measures which predominate in Western
      medicine. Strategies for the development and use of assessment questionnaires
      have evolved over the past 15 years, and numerous questionnaires have been
      created. Most originate in Western societies, with English as the most common
      language of development. Adapting such questionnaires for use in other language
      and cultural settings is an imprecise practice. Language translation and
      equivalent cultural meaning must both be addressed. This paper reports on the
      language translation process and results for the Functional Living Index for
      Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a
      step-wise process beginning with translation/back translation, followed by
      structured pilot field trials and population sampling. Taped versions of the
      questionnaire were devised to meet illiteracy problems in the sample population.
      Paired comparisons of the Chinese and Malay versions of individual questions with
      their English counterparts show good correlations and similar means most of the
      time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98
      English speaking) with cancers of minimal, extensive or palliative extent is
      convergent with that obtained on a North American population. However, a separate
      analysis of the Chinese questionnaires showed some differences in factor pattern.
      Specific language and cultural translation difficulties are discussed. Of note is
      the predicted significant decrease in total FLIC scores with extent of disease
      within each of the language preference populations, which provides some evidence
      for the validity for each language version in the Singapore culture(s). Thus, the
      FLIC translations into Malay and Chinese in Singapore can be considered for use
      in local trials, subject to ongoing evaluation.

PMID- 8876897
TI  - Altered fractionated radiation therapy for head and neck carcinomas--A
      Massachusetts General Hospital experience.
AB  - This paper discusses the various forms of altered fractionated radiation therapy
      programmes which were used in the past and at present. Treatment programmes
      employing large fraction sizes and prolonged treatment course result in severe
      late complication of the normal tissues and inferior local tumour control
      respectively, and are no longer advised. The current radiobiologic concepts of
      altered fractionationated treatment are briefly discussed. The experiences of
      using accelerated hyperfractionated radiation therapy programme for the treatment
      of oropharyngeal and laryngeal carcinomas at the Massachusetts General Hospital
      (MGH) from 1979 through 1994 are presented. The programme consists of 1.6 Gy/f
      twice-daily (BID) for approximately 67.2-70.4 Gy in 6 weeks with a short 'break'
      after the initial 38.4 Gy. The local control and disease specific survival rates
      after BID are reported related to the various stages of the lesions and compared
      with historical control of once-daily (QD) radiation therapy at the MGH. The data
      thus far indicated higher local control and disease specific survival after BID
      radiation therapy for advanced carcinomas (T2-3 lesions). The therapeutic gains,
      however, did not occur significantly for early lesions (T1 disease). The
      importance of the effects of the total doses and total treatment time, related to
      the treatment outcome, is discussed.

PMID- 8876898
TI  - Patient profile and survival in 270 computer tomography-staged patients with
      nasopharyngeal cancer treated at the Singapore General Hospital.
AB  - This is a report analysing the patient profile and survival results in 270
      patients with nasopharyngeal carcinoma treated with radiation therapy between
      July 1987 and December 1988. The patients had a median age of 52.6 months, and a
      male-female ratio of 2.5:1. Ninety-four percent of patients were Chinese. The
      commonest presentation was that of a neck mass (found in approximately 65% of
      patients). Approximately two-thirds presented with disease more advanced than
      Ho's stage II. At a median follow-up of 52.6 months, the 5-year actuarial
      survival rate was 53% and the freedom from relapse rate was 57%. One hundred and
      seven patients died within the observation period. Of these, 46 patients had
      disease in the post nasal space, 41 in the neck and 60 in sites outside the head
      and neck.

PMID- 8876899
TI  - Preliminary experience of infusional brachytherapy using colloidal 32P.
AB  - In the past, we have clinically evaluated radiolabelled antibodies in Hodgkin's
      disease and hepatocellular cancer. Increased tumour pressure, reduced vascularity
      and poor diffusion has limited significant radiolabelled antibody tumour dose
      deposition. Using intratumoural infusion of macroaggregated albumin to blockade
      exiting vasculature followed by colloidal chromic 32Phosphorous, we have been
      able to achieve 75% to 100% tumour dose deposition by interstitial tumour
      infusion under computerised tomographic guidance. Phase I studies in a variety of
      solid tumours indicate extremely high doses may be achieved without toxicity
      (i.e. non-resectable pancreas 900,000 cGy to 1.7 million cGy) with tumour control
      and remission. This is a review of those studies and how the technique was
      applied.

PMID- 8876900
TI  - Kyoto University experience with intraoperative radiation therapy.
AB  - To date, intraoperative radiotherapy has been performed at Kyoto University
      Hospital in a total of 480 patients with malignancies various sites. Among these,
      patients with disease of 4 major sites were selected for prognostic analysis. For
      gastric cancer patients survival was improved by the adjuvant intraoperative
      radiotherapy compared with gastrectomy alone in those with advanced nodal or
      serosal involvement [P < 0.05 for n2 + n3' 0.1 > P > 0.05 for s(+)]. Also, the
      survival for the adjuvant radiotherapy group was significantly improved in
      patients with stage II-III pancreatic cancer who underwent non-curative resection
      (P < 0.001). For patients with soft tissue sarcomas of the extremities,
      intraoperative radiotherapy was performed after the tumours were surgically
      removed to the greatest e* possible. Operation curability had a great impact on
      the local tumour control rate (82% for curative resection versus 18% for non
      curati resection) and on the long-term survival rates (65% versus 8%,
      respectively). In patients with osteosarcoma, a large single do* 50-55 Gy was
      applied to the affected limb in an attempt to achieve local control and limb
      salvage. By this method, good local control attained, and a 10-year survival rate
      showed improvement following the introduction of cisplatinum into intensive
      chemotherapy.

PMID- 8876901
TI  - Localised nodal non-Hodgkin's lymphoma--a study of 42 cases treated by
      radiotherapy.
AB  - The records of 42 patients with stage I and II nodal non-Hodgkin's lymphoma
      treated by radiotherapy with and without chemotherapy were analysed with regards
      to clinical presentation, investigations, treatment, radiotherapy techniques and
      results. The 5-year overall survival rates for all, low grade, intermediate grade
      and high grade histology types are 69.5%, 100%, 64.4% and 46.9% respectively. The
      5-year relapse-free survival rates of those treated by initial radiotherapy alone
      for all, low grade and intermediate-high grade histology types are 54.8%, 46.9%
      and 59.4% respectively.

PMID- 8876902
TI  - Testicular seminoma--the results of treatment by radiotherapy in Singapore.
AB  - A retrospective analysis was done of 49 patients treated for testicular seminoma
      over a 15-year period between January 1980 and April 1995 at the Department of
      Therapeutic Radiology, Singapore General Hospital. Their mean age was 39 years
      and their median period of follow-up was 67 months. Using the Royal Marsden
      Staging classification, 35 (71.4%) were stage I, 10 (20.4%) were stage II, I (2%)
      was stage III, and 3 (6.1%) were stage IV. Five (10.2%) arose in undescended
      testes. Thirty-six patients were treated with inguinal orchidectomy and
      postoperative radiotherapy to the para-aortic and ipsilateral iliac nodes. Eight
      had para-aortic and bilateral iliac irradiation, and 2 had ipsilateral pelvic,
      para-aortic, mediastinal and supraclavicular lymph node irradiation. Six of the
      patients had, in addition, irradiation of the inguinal-scrotal area. Nine
      received both chemotherapy as well as radiotherapy. The median dose of radiation
      given was 30.67 Gy and where a boost was required, the median total tumour dose
      was 35.75 Gy. The actuarial relapse-free survival at 10 years was 88.9% and the
      actuarial overall survival at 10 years was also 88.9%. Long-term treatment
      toxicities were uncommon.

PMID- 8876903
TI  - Radical radiotherapy for carcinoma of the uterine cervix using high dose rate
      brachytherapy--a preliminary report.
AB  - From April 1992 to December 1994, a total of 61 patients with carcinoma of the
      cervix were treated with curative intent using initially external beam therapy
      followed by high dose rate brachytherapy. On reviewing 57 patients with adequate
      follow-up data, the local failure rate was found to be 12.3% and metastatic
      failure rate was 15.8%. Local pelvic failure rates for stage II and III patients
      were 10% and 13.6% respectively, but for stage I disease, there was one local
      failure out of 5 patients, at a rate of 20%. This is probably due to the small
      number in this subgroup. Complication rate was low with only one patient with
      grade IV problems, giving a serious complication rate of 1.7% only. Overall
      actuarial rate in this group was 50.1%. These results are encouraging but further
      review on achieving adequate follow-up is needed before firm conclusions can be
      drawn.

PMID- 8876904
TI  - The role of radiotherapy in the management of cancer--an overview.
AB  - Artificial X-rays were first produced in Germany in 1895 and used for cancer
      almost immediately. During the century since this remarkable discovery, radiation
      therapy has now become the most imporantant non-surgical modality in cancer: over
      50% of all cancer patients now receive radiotherapy at some point during the
      illness. Radiation therapy has increasingly replaced surgical resection for
      primary control of a variety of solid tumours, particularly where surgical
      excision is accompanied by severe long-term tissue loss or psychological
      morbidity. Frequent examples include cancers of the breast, head and neck
      (especially larynx, naso- and other pharyngeal sites), and locally advanced
      cancer of the cervix. Combinations of surgery and radiotherapy are increasing
      used, for example in the preferred management of most cancers of the breast, by
      wide local surgical excision, breast preservation and postoperative radiotherapy.
      In rectal carcinoma as well, there is clear evidence of survival improvement in
      locally advanced cases when surgical excision is followed by routine pelvic
      irradiation. In other circumstances, radiation is routinely combined with
      chemotherapy, as for example in the standard management of small cell lung
      cancer. Anal carcinoma is also best treated by radical radiochemotherapy,
      avoiding surgical excision (with permanent colostomy) in the majority of
      patients. In both the developed and developing world, these are all common
      tumours, with the result that in 1990, almost half a million patients were
      treated with radiation therapy in the United States of America. Recent technical
      advances, both in imaging and therapy beam precision, have greatly improved the
      therapeutic ratio and accuracy of modern radiotherapy. Radiation therapy
      continues to progress on a rational scientific basis, with a secure clinical role
      for the foreseable future.

PMID- 8876905
TI  - Oncological problems in AIDS--a review of the clinical features and management.
AB  - Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic in
      the early 1980s, several malignant conditions have been recognised to be
      associated with this syndrome which affect up to 40% of AIDS patients at some
      stage of their illness. They include Kaposi's sarcoma, systemic non-Hodgkin's
      lymphoma, primary central nervous system lymphoma and invasive cervical cancer.
      Kaposi's sarcoma and primary central nervous system lymphoma were tumours rarely
      seen below the age of 50 prior to the epidemic and therefore were recognised
      early to be AIDS-related conditions. However, systemic non-Hodgkin's lymphoma and
      invasive cervical cancer were only recognised when sufficient epidemiological
      evidence became available to indicate an increased incidence of these conditions
      amongst the HIV-infected population. In the presence of immunosuppression, the
      biological behaviour of these conditions are significantly altered with a more
      advanced stage at presentation, a more aggressive disease course and poorer
      responses to treatment. There is evidence that in each of these malignant
      conditions, an additional viral infection may be responsible for their
      pathogenesis. Kaposi's sarcoma-associated herpes virus is implicated in the
      development of Kaposi's sarcoma, Epstein-Barr virus in systemic non-Hodgkin's
      lymphoma as well as primary central nervous system lymphoma and human papilloma
      virus in invasive cervical cancer. Developing effective treatment strategies with
      minimal toxicity for these patients remains the greatest challenge as they often
      have serious coexisting illnesses and tolerate chemotherapy poorly because of
      insufficient bone marrow function reserve.

PMID- 8876906
TI  - Supratentorial low-grade glioma: is there a role for radiation therapy?
AB  - The supratentorial low-grade gliomas are a heterogeneous group of central nervous
      system tumours. Knowledge of their biology, primarily based on histologic subtype
      and patient age, is helpful in determining prognosis and guiding therapeutic
      recommendations. The pilocytic tumours usually occur in younger patients and
      carry a favourable prognosis. Recurrence following gross total excision is rare,
      and approximately 80% of patients undergoing subtotal removal with or without
      postoperative radiation therapy (RT) will survive 10 years or longer. In
      contrast, non-pilocytic, supratentorial low-grade tumours (including the diffuse
      fibrillary, protoplasmic and gemistocytic subtypes), as well as mixed
      oligoastrocytomas and oligodendrogliomas are infrequently cured, even with gross
      total excision. Survival benefit with postoperative RT has been suggested by
      several retrospective studies. When RT is prescribed, localized treatment fields
      are suggested for total doses of 4500 to 6500 cGy. Ongoing prospective,
      randomized studies hopefully will clarify the role of RT in these neoplasms, as
      well as the optimal dose.

PMID- 8876907
TI  - Hypoxic sensitizer and cytotoxin for head and neck cancer.
AB  - Tumour hypoxia is well recognised as a major factor contributing to
      radioresistance. This article examines the role of hypoxia in influencing the
      treatment outcome following radiotherapy (RT), and reviews the rationale and
      results of clinical trials that utilise hypoxic sensitizers or cytotoxins in the
      treatment of head and neck carcinoma. Histologic evidence for tumour hypoxia in
      human neoplasms was first reported in 1955. Since then, direct measurement by
      microelectrodes has revealed heterogeneity in intratumoural oxygen
      concentrations, and low oxygen concentrations are associated with poor local
      regional control by RT. These findings coupled with the result of nuclear imaging
      studies employing radiolabelled imidazoles, provide strong evidence for the
      existence of tumour hypoxia which influences RT treatment outcome. Hyperbaric
      oxygen (HBO) trials for head and neck cancer, conducted in the early 1970s,
      demonstrated that HBO improved local control and survival rates in patients with
      head and neck cancer receiving radiotherapy (RT). Since the mid-1970s, clinical
      research in overcoming tumour hypoxia was mainly centred on the use of nitro
      imidazoles as hypoxic cell sensitizers. However, the results from several major
      clinical trials remain inconclusive. Specifically, the Radiation Therapy Oncology
      Group (RTOG) misonidazole head and neck trial (298 patients) showed no benefit.
      The Danish misonidazole trial (626 patients) showed no overall benefit, however
      positive results were observed in a subgroup (304 pharyngeal cancer patients).
      Although the European Organisation for Research and Teaching of Cancer (EORTC)
      misonidazole trial with hyperfractionated RT showed no benefit, the Danish
      nimorazole trial demonstrated an overall benefit in survival as well as local
      control. The European etanidazole (ETA) trial (374 patients) showed no advantage
      of adding the drug to RT. The RTOG ETA trial (504 patients) showed no global
      benefit. However, positive results were observed in a subset of patients with
      early nodal disease (197 patients). In addition, a recent meta-analysis by
      Overgaard, utilising pooled results in the literature demonstrated that
      modification of tumour hypoxia significantly improved local-regional control in
      head and neck cancers with an odds ratio of 1.23 (95% confidence limits 1.09 to
      1.37). Hypoxic cytotoxins, such as tirapazamine, represent a novel approach in
      overcoming radioresistant hypoxic cells. Tirapazamine is a bioreductive agent
      which, by undergoing one electron reduction in hypoxic conditions, forms
      cytotoxic free radicals that produce DNA strand breaks causing cell death. In
      vitro and in vivo laboratory studies demonstrate that tirapazamine is 40 to 150
      times more toxic to cells under hypoxic conditions as compared to oxygenated
      conditions and that tirapazamine is superior to ETA in enhancing fractionated
      irradiation in mouse SCCVII and other tumour types with an enhancement ratio of
      1.5 to 3.0. Phase I studies demonstrated that therapeutic doses of tirapazamine
      can be given safely. A multi-institutional phase II trial using tirapazamine with
      concurrent RT for head and neck cancer is now in progress.

PMID- 8876908
TI  - Multidisciplinary management controversies in laryngeal cancer.
AB  - While the primary goal of laryngeal cancer management is to save life, the
      preservation of structure and function also holds a very prominent position in
      the decision making for this disease. Although the therapeutic options to achieve
      these goals exist for most patients presenting with laryngeal carcinoma, they are
      not applied to a significant number of patients. In this paper we will summarise
      some of the disagreements which exist about optimal management and demonstrate
      that the opinions of experts trained to treat this disease have been shaped by
      non-evidence based approaches. In large part the specialty of practice and the
      geographic location of specialists have the greatest influence on the type of
      treatment recommended to an individual patient with a given stage of disease;
      medical knowledge, or more correctly the lack of it when comparing treatment
      options, seems to have a lesser influence on the decision process. We will
      consider the principal opportunities available to attempt to resolve
      controversies in laryngeal cancer. The discussion will include attention to
      randomised clinical trials, patient preferences, economic issues, and techniques
      to avoid the problems of selection bias when comparing outcomes for different
      treatments.

PMID- 8876909
TI  - Radiotherapy in the management of thyroid cancer.
AB  - Surgery is the definitive and potentially curative treatment for the slow growing
      well-differentiated papillary and follicular carcinomas. Total (or near-total)
      thyroidectomy is required, together with excision of adjacent lymph nodes when
      involved, or a modified block dissection if there is extensive lymphatic
      involvement. Ablation of residual normal thyroid with radioactive iodine usually
      follows as this will permit subsequent whole-body I-131 scanning to exclude the
      presence of residual or metastatic disease. Normally such patients have an
      excellent prognosis and can be followed simply with serum thyroglobulin
      estimations. Occasionally therapeutic radioactive iodine is necessary to
      eradicate metastatic disease. The anaplastic carcinomas grow and metastasise with
      explosive rapidity. They are typically inoperable at presentation and have no
      ability to concentrate iodine. Prognosis is appalling with external beam
      radiotherapy providing only palliation. Medullary carcinoma is different again as
      it arises from the parafollicular or C-cells. Total thyroidectomy must be
      undertaken as these tumours may be multifocal; a central compartment neck
      resection is ideally undertaken at the same time, together with a formal block
      dissection if lymph node disease is found to be present. External beam
      radiotherapy is often required. These tumours can be inherited and produce the
      tumour marker calcitonin. The rarest group of thyroid cancer is the lymphomas.
      Like the anaplastic carcinomas, they grow very rapidly but, unlike the former,
      are radio-responsive. The additional use of chemotherapy is necessary when they
      are of advanced stage or demonstrate poor prognostic factors.

PMID- 8876910
TI  - The present status of hyperthermia in Japan.
AB  - The research on hyperthermia in Japan was started by the Hyperthermia Study Group
      in 1978. Six years later, in 1984, the Japanese Society of Hyperthermic Oncology
      (JSHO) was established. More and more research has been conducted since then. At
      present, 215 units of heating equipment are installed for use. Among these, 24%
      are microwave heating equipment, and 66% are radiofrequency (RF) capacitive
      heating equipment. A nation-wide survey has revealed that about 60% of
      hyperthermia therapy involves the treatment of deep-seated tumours by RF
      capacitive heating and RF intracavitary heating. The treatment of superficial
      tumours by microwave heating represents another 12.5%. Most of the clinical
      application in the United States and in Europe is microwave heating of
      superficial tumours. The different modalities of treatment were
      thermoradiotherapy in 57.5%, thermochemotherapy in 22.6% and
      thermochemoradiotherapy in 14.5% of the cases surveyed. Compared to other
      countries, Japan has the highest number of hyperthermia equipment installed, and
      the most doctors involved in hyperthermia therapy. The main reasons for the
      advanced state of hyperthermia research in Japan include the development of
      excellent heating equipment, high membership in JSHO, grant-in-aid by the
      Japanese government, and coverage by insurance for this form of therapy. Based on
      33 papers selected from two books which the author had edited, the optimal
      protocol, effectiveness and indication for the use of hyperthermia has been
      established.

PMID- 8876911
TI  - Radiotherapy in Wilms' tumour.
AB  - Radiotherapy in the treatment of Wilms' tumour has had a long and distinguished
      history. In the pre-chemotherapy era, it was shown that radiotherapy given
      postoperatively increased the survival of patients with this disease. As Wilms'
      tumour is highly chemosensitive, the use of radiotherapy has been modified and it
      is now clear that it is not necessary for patients with stage I and II favourable
      histology (approximately 60% of all patients with Wilms' tumour). No dose
      response has been demonstrated for radiotherapy in Wilms' tumour; therefore, the
      National Wilms' Tumor Study protocols use 10 Gy. Results from the International
      Society of Pediatric Oncology and United Kingdom Children's Cancer Study Group
      have shown that radiotherapy must continue to be used in certain circumstances.

PMID- 8876912
TI  - Is there a place for whole abdominal radiotherapy in the management of ovarian
      cancer?
AB  - Most patients with ovarian cancer require further therapy with chemotherapy or
      radiotherapy because of the high recurrence risk following surgery alone.
      Radiotherapy directed to the whole abdomen and pelvis is capable of producing
      survival rates of 70% in carefully selected patients. Such patients have no more
      than microscopic residual disease in the abdomen, and small volume residual
      disease in the pelvis. They are selected based on a prognostic matrix which
      considers grade, stage and the presence of pelvic residual disease. With optimal
      radiotherapy technique, long term serious toxicity occurs in less than 5% of
      patients. Patients with macroscopic residual disease are treated with
      chemotherapy. Patients who obtain a complete response have been treated with
      consolidative whole abdominal radiotherapy, although the benefit of such an
      approach is unclear.

PMID- 8876913
TI  - The role of radiotherapy in endometrial carcinoma.
AB  - The purpose of this work is to describe the role of radiotherapy in endometrial
      carcinoma. Endometrial carcinoma is a common, invasive gynaecologic malignancy
      that kills thousands of women throughout the world each year. This tumour is
      especially common in developed countries. The use of radiotherapy in these
      patients may consist of preoperative irradiation, irradiation alone or
      postoperative irradiation. The use of irradiation has changed significantly over
      time and the use of a specific radiotherapy modality depends on many factors,
      including local geographic practice patterns. The evolving use of pre and
      postoperative irradiation will be described. Whole abdominal irradiation and the
      use of irradiation alone in medically inoperable patients will be discussed.
      Current prospective randomised studies within the United States will be presented
      and discussed.

PMID- 8876914
TI  - Organ preservation approaches with radiation therapy in muscle-invasive bladder
      carcinoma.
AB  - Combined modality treatments with organ preservation intent have become standard
      oncological treatment in many tumour sites. Although radical cystectomy had been
      considered to be the standard treatment, combined modality treatment has been
      used in muscle-invasive bladder carcinoma with excellent results, especially in
      patients with T2-3a disease without obstructed ureters. The components of the
      combined treatment are usually transurethral resection of bladder tumour (TURBT)
      followed by concurrent chemotherapy and radiation. Interim cystoscopic assessment
      after the initial portion of radiation is often utilised to identify patients at
      high risk of local failure, ie. those who do not achieve a complete response, and
      these patients are then recommended to undergo immediate salvage cystectomy.
      Delaying cystectomy does not appear to decrease the survival or increase the
      incidence of distant metastasis. The local control rates for TURBT alone,
      chemotherapy alone and radiation therapy alone are only 20%, 20% and 30% to 45%
      respectively. When the above three are combined together, a complete response
      rate of 75% can be achieved and 85% of these remain free from invasive
      recurrence. Combined modality treatment offers an overall survival rates which is
      comparable with modern radical cystectomy series: about 50% at 5 years, and in
      addition, it offers a 5-year survival rate with an intact bladder of 41% to 43%.
      With the close collaboration among urologists, medical oncologists and radiation
      oncologists, organ preservation approaches can achieve excellent results in
      muscle-invasive bladder carcinoma and this option should be presented to patients
      as an alternative to radical cystectomy.

PMID- 8876915
TI  - Indications for and results of irradiation +/- chemotherapy for rectal cancer.
AB  - With mobile rectal cancers, surgery alone is insufficient treatment for most
      patients with high-risk factors of tumour extension beyond the rectal wall, node
      involvement, or both in conjunction. While single modality adjuvant treatment
      with pre- or postoperative irradiation can reduce the incidence of local relapse,
      a statistically significant impact on survival has not been achieved. Combined
      modality postoperative chemoirradiation has resulted in both improved disease
      control (local and distant) and improved survival (disease free and overall).
      Randomized trials are underway in high-risk patients to determine the most
      optimal combinations of postoperative chemoirradiation and to compare
      preoperative versus postoperative chemoirradiation. Standard therapy with
      surgery, external irradiation, and chemotherapy is often unsuccessful for
      patients with locally advanced primary cancers that are unresectable for cure or
      locally recurrent cancers. When intraoperative electron irradiation is combined
      with standard treatment, encouraging trends are seen with regard to improvements
      in local control and survival in separate analyses from the Mayo Clinic and the
      Massachusetts General Hospital. More standard use of systemic therapy is needed
      as a component of treatment, however, in view of high rates of systemic failure
      in spite of the locally aggressive treatment regimens.

PMID- 8876916
TI  - Anal canal cancer: current treatment and results.
AB  - Combined radiation and chemotherapy is established as the preferred treatment for
      primary epidermoid cancer of the anal canal. This approach allows preservation of
      anorectal function without any apparent decrease in the survival rates obtained
      in the past with radical surgery. Most experience has been gained with radiation,
      5-Fluorouracil (5-FU) and mitomycin C, but radiation, 5-FU and cisplatin are also
      effective. Regional lymph node metastases can be eradicated by radiation and
      chemotherapy, but cancers which have metastasized to regional nodes or to
      extrapelvic organs carry a poor prognosis. Extrapelvic metastases and recurrent
      pelvic cancer respond poorly to systemic chemotherapy, and to combinations of
      radiation and chemotherapy. Cisplatin combined with 5-FU is the most effective
      treatment presently available in such situations. No effective systemic adjuvant
      therapy has yet been devised.

PMID- 8876917
TI  - Nuclear energy facilities and cancers.
AB  - Workers employed in the nuclear energy industry and members of the general public
      living near nuclear facilities are exposed to low levels of ionising radiation as
      a result of the routine operation of these facilities. For the purposes of
      radiological protection, it is assumed that low doses of radiation confer a small
      increased risk of cancer upon the exposed individual and this is a major
      consideration in setting dose limits for workers and the general public.
      Quantitative estimates of radiation risk have been derived from epidemiological
      studies of groups exposed, on average, to high or moderate doses of radiation
      (such as the Japanese atomic bomb survivors), and appropriate assumptions are
      made for the application of such estimates to low dose conditions. There have
      been claims that the risks of cancer in nuclear industry workers, in their
      children, and in populations living around nuclear facilities have been grossly
      underestimated. Substantial evidence is now available from the epidemiological
      study of these groups. Studies of nuclear industry workforces demonstrate that
      currently accepted risk estimates are at about the right level, although a
      positive trend of leukaemia mortality with radiation dose, of a magnitude which
      is compatible with predictions, can be detected in the most statistically
      powerful workforce studies. The hypothesis that irradiation of fathers before the
      conception of their children materially increases the risk of childhood leukaemia
      has been largely discounted since it is biologically implausible and has found no
      support in studies using data independent of the study which generated the
      hypothesis. Increased levels of childhood leukaemia have occurred near certain
      nuclear facilities in the United Kingdom, but it is most unlikely that these are
      related to exposure to ionising radiation. Recent evidence suggests that these
      excesses are caused by a rare response to an infectious agent, which is enhanced
      under the unusual conditions of population mixing found in these communities.
      Similar excesses of childhood leukaemia have been found in other communities
      which have experienced unusual population mixing, but are not near nuclear
      facilities.

PMID- 8876918
TI  - Laparoscopic applications for abdominal trauma injuries.
AB  - Laparoscopy has been shown to be an effective diagnostic and therapeutic modality
      for trauma patients. The benefits of laparoscopic intervention include the
      avoidance of negative laparotomy procedures, decreased patient morbidity rates,
      shorter hospital stays, and lower costs. Laparoscopic limitations are discussed
      in this article as well as the perioperative nursing considerations in all phases
      of trauma patients' care. Five case studies in which patients' care was enhanced
      by the use of laparoscopy are presented.

PMID- 8876919
TI  - Management of retrohepatic venous injuries with atrial caval shunts.
AB  - Retrohepatic inferior vena caval injuries resulting from blunt or penetrating
      abdominal trauma are rare but devastating events that remain formidable
      challenges to even the most experienced Level I trauma center team members.
      Prepackaged atrial caval shunts have improved emergency medical treatments, and
      prior planning and coordination by perioperative nurses allow for rapid response
      by surgical team members. These efforts provide an optimal level of care required
      to increase patient survival. This article provides a general overview of
      abdominal trauma and retrohepatic inferior vena caval injuries and a proactive
      plan to meet the needs of patients with these injuries.

PMID- 8876920
TI  - Perioperative nursing care of patients with craniofacial injuries.
AB  - Craniofacial injuries are the result of deceleration, blunt, or penetrating
      trauma. Depending on the mechanism of injury, craniofacial fractures can be minor
      and go undetected, or they can produce devastating facial deformities. With the
      advent of intermaxillary fixation devices, surgeons can manipulate facial bone
      structures and repair soft tissue damage in the majority of patients with
      craniofacial trauma injuries. Most patients experience optimal results from their
      craniofacial surgical procedures and return to normal lives after surgery.

PMID- 8876921
TI  - Choreographing trauma resuscitation in the OR.
AB  - Survival rates are enhanced if severely injured trauma patients are admitted
      directly to the OR for resuscitation and surgical intervention. To increase the
      survivability and decrease the morbidity of trauma patients with penetrating
      trauma to the chest or abdomen, a hospital in La Jolla, Calif, developed a
      "direct to the OR" resuscitation program. This program substantially increased
      the survival rate of these trauma patients. Perioperative nurses respond to all
      major trauma situations and assist with surgical procedures completed in a trauma
      resuscitation room or in the OR.

PMID- 8876922
TI  - Intraoperative progress reports decrease family members' anxiety.
AB  - The researcher used a four-group quasi-experimental posttest design to examine
      the effect of intraoperative progress reports on 200 family members' anxiety.
      Group one (ie, control group) received standard perioperative care, which did not
      include intraoperative progress reports. Group two received in-person progress
      reports from perioperative nurses. Group three received an "attention" protocol
      (ie, checklist explaining hospital routines, waiting room procedures). Group four
      received progress reports delivered by telephone. The researcher compared family
      members' state anxiety scores, mean arterial pressures (MAPs), and heart rates
      measured halfway during their relatives' surgical procedures, measuring these
      dependent variables after providing the interventions. The in-person
      intraoperative progress report group reported lower state anxiety scores (P <
      .001) and had significantly lower MAPs and heart rates (P < .05) than the other
      three groups. In-person progress reports appear to be the most beneficial
      perioperative nursing intervention for reducing family members' anxiety during
      the intraoperative waiting period.

PMID- 8876923
TI  - Preparing an OR for level II trauma designation.

PMID- 8876924
TI  - Nursing Research Committee replicates 1988 staffing study in the summer of 1995,
      finds little change at that time.

PMID- 8876925
TI  - Abusive behavior in the perioperative setting.

PMID- 8876926
TI  - Protease inhibitor approved for AIDS treatment.

PMID- 8876927
TI  - Reporting requirements under the Safe Medical Devices Act.

PMID- 8876928
TI  - Nurses' guide to the Internet--professional and personal benefits.

PMID- 8876930
TI  - Cerebral blood flow effects of piracetam, pentifylline, and nicotinic acid in the
      baboon model compared with the known effect of acetazolamide.
AB  - In normal aging humans there is a progressive decrease of oxygen and glucose
      consumption with a reduction of cerebral blood flow (CBF), which could be
      responsible for age-related changes in cognitive functions. A baboon model under
      anaesthesia using single photon emission computed tomography (SPECT) of the brain
      and the radiopharmaceutical hexamethylpropylene amine oxime (99mTc-HMPAO) has
      been developed and found to be sensitive to the effects of drugs that are known
      to increase CBF. In the present study, the effect of two haemorrheologically
      active drugs, viz a combination of pentifylline (CAS 1028-33-7) and nicotinic
      acid (CAS 59-67-6) vs. piracetam (CAS 7491-74-9) were compared with the known
      effect of acetazolamide (CAS 59-66-5) on CBF in the baboon model using the 99mTc
      HMPAO split dose method. Acetazolamide (p < 0.05) and the combination of
      pentifylline and nicotinic acid (p < 0.01) increased the CBF when compared with
      the control baseline. The CBF was not significantly increased upon treatment with
      piracetam, pentifylline alone and nicotinic acid alone, when compared with the
      control values for total brain ratios (p > 0.05). However, an increased regional
      effect was observed for piracetam. These results indicate that the above
      haemorrheologically active drugs exhibit specific but different effects on
      cerebral blood flow with possible clinical implications.

PMID- 8876929
TI  - Absorption of the anxiolytic pazinaclone in animals as a criterion for species
      selection for toxicity studies.
AB  - In rats, mice, hamsters, and guinea pigs given a 5 mg/kg oral dose of pazinaclone
      (CAS 103255-66-9), unchanged drug concentration in plasma was highest in mice
      (AUC; 90 ng.h/ml), followed in decreasing order by guinea pigs (AUC; 41 ng.h/ml),
      hamsters (AUC; 18 ng.h/ml), and rats (AUC; 17 ng.h/ml). In terms of plasma drug
      concentrations and toxicological background data, there was no better alternative
      rodents than mice and rats for the toxicity studies. Among rabbits, dogs, and
      monkeys, the dogs had the highest plasma drug concentrations: AUCs of pazinaclone
      in dogs and monkeys were 1035 and 458 ng. h/ml, respectively (drug concentration
      in rabbit plasma was very low). Of the two polymorphs, forms 1 and 2 with
      particle size of < or = 5 microns, the oral absorption of form 2 in rats was more
      efficient than that of form 1 at 1000 mg/kg: AUCs of pazinaclone after dosing of
      form 1 and 2 were 489 and 965 ng.h/ml, respectively. However, form 1 was selected
      for the toxicity studies because of the poor physico-chemical properties of forms
      2. Form 3 was not included in this study, because this form was relatively
      unstable and contained relatively large amount of impurities. The absorption of
      pazinaclone in dogs was improved by decreasing its particle size: AUCs of
      pazinaclone after dosing of the drug having particle size of 5.5, 20.8, and 79.3
      microns were 1361, 822, and 297 ng.h/ml, respectively. Since large-scale
      preparation of bulk pazinaclone with a particle size of 5 microns or smaller was
      not feasible, the drug having a particle size of about 20 microns was used in the
      toxicity studies. The absorption of pazinaclone was more extensive when the drug
      was given to fed animals as suspension. Thus, the toxicity studies were performed
      using form I of pazinaclone with a particle size of about 20 microns primarily in
      rats, mice, and dogs.

PMID- 8876931
TI  - Synthesis and pharmacological profile of some chloroxanthone-1, 4-dihydropyridine
      derivatives.
AB  - A series of xanthone-1,4-dihydrophyridine derivatives bearing a chlorine atom in
      the xanthone nucleus was prepared. The compounds were evaluated for inotropic,
      chronotropic and calcium antagonist properties. The chlorine introduction in the
      xanthone moiety slightly affected affinity for cardiac vs. vascular tissues
      improving to some extent selectivity.

PMID- 8876933
TI  - Comparative antioxidant and cardioprotective effects of ceruloplasmin, superoxide
      dismutase and albumin.
AB  - The antioxidant effects of ceruloplasmin (CAS 9031-37-2) against oxygen free
      radicals (.O2-, .OH, 1O2) and their by-products (H2O2, HOCl), generated by
      electrolysis of Krebs-Henseleit buffer, were determined in vitro by the DPD (N,N
      diethyl-p-phenylenediamine) colorimetric method and ex vivo by quantifying
      cardiodynamic variables of the isolated perfused rat heart. Purified
      ceruloplasmin (1 mumol/l) displayed a high antioxidant capacity in vitro (89.2%),
      while the scavenging capacity of superoxide dismutase (SOD) in equimolar
      concentrations was 38.1%. A relatively high scavenging activity (72.1%) was
      observed with bovine serum albumin (BSA). A control group of Langendorff isolated
      rat hearts (n = 8) was submitted to electrolysis (10 mA, for 1 min) without
      treatment, whereas the treated groups were perfused with ceruloplasmin, SOD or
      BSA (1 mumol/l) in the inflow cannula for 5 min before, during, and 5 min after
      electrolysis. The cardioprotective effect afforded by ceruloplasmin (83-89%) was
      higher than that observed with the same optimal dose of 1 mumol/l SOD (20-45%).
      With BSA, no protection was observed ex vivo. Particularities in scavenging
      specificities and mechanisms seem to explain the important differences between in
      vitro and ex vivo antioxidant capacities for these proteins.

PMID- 8876932
TI  - Effects of efonidipine, nicardipine and captopril on proteinuria in aged
      spontaneously hypertensive rats.
AB  - Previous studies have shown that antihypertensive drugs attenuate the progression
      of proteinuria by their treatments from young age, but few have examined their
      effects on impaired renal function in older age. In the present study the calcium
      antagonists efonidipine ((+/-)-2-[benzyl (phenyl)amino]ethyl 1,4-dihydro-2,6
      dimethyl-5-(5,5-dimethyl-2-oxo-1,3, 2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3
      pyridinecarboxyla te hydrochloride ethanol, CAS 111011-76-8, NZ-105) and
      nicardipine, and an angiotensin-converting enzyme inhibitor, captopril, were
      examined for their effects on heavy proteinuria in aged spontaneously
      hypertensive rats (SHR). Efonidipine (20 mg/kg), nicardipine (20 mg/kg) and
      captopril (30 mg/kg) were orally administered once a day for 4 weeks. The urinary
      protein excretion (UproE) increased with age (54.9 mg/kg/day at 24 weeks of age
      to 170.8 mg/kg/day at 36 weeks). The increased UproE was significantly suppressed
      by daily administration of efonidipine or captopril as compared to that in the
      non drug treated control group. The UproE in the nicardipine group was maintained
      at a slightly lower level than in the control. The histological examination
      showed that the damages of the kidneys were slightly suppressed by efonidipine
      and captopril. These findings indicate that efonidipine as well as captopril
      reduce proteinuria in aged SHR and the effect was stronger than that of
      nicardipine. This beneficial effect of efonidipine on proteinuria suggests its
      usefulness in antihypertensive therapy.

PMID- 8876934
TI  - Effects of the new calcium antagonist efonidipine hydrochloride on resting and
      exercise hemodynamics in patients with stable effort angina.
AB  - The action of efonidipine hydrochloride ((+/-)-2-[benzyl(phenyl)-amino]ethyl 1,4
      dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1, 3,2-dioxaphosphorinan-2-yl)-4-(3
      nitrophenyl)-3-pyridinecarboxy late hydrochloride ethanol, CAS 1110011-76-8, NZ
      105) a new dihydropyridine calcium antagonist, on cardiac hemodynamics at rest
      and during exercise as well as plasma concentration and pharmacokinetic
      parameters were studied in 9 patients with angina pectoris. NZ-105 was
      administered 40 mg once daily for a week and cardiac hemodynamics parameters were
      measured at rest and during exercise using a bicycle ergometer before and after
      treatment. All patients showed anginal symptoms during exercise before treatment,
      while only 4 showed anginal symptoms during exercise after treatment. Improvement
      on electrocardiograms (ECG) (> 0.1 treatment mV) was detected in 4 out of 9, and
      NZ-105 was recognized to have an anti-anginal action. The mean plasma
      concentration of NZ-105 at the time was 14.5 ng/ml. At rest, reduction in blood
      pressure and decrease in total peripheral vascular resistance were observed,
      however, NZ-105 showed no effect on heart rate, cardiac index, pulmonary arterial
      pressure and central venous pressure. During maximum exercise, a decrease in
      total peripheral vascular resistance, reduction in pulmonary arterial pressure
      and central venous pressure, increasing tendency of left ventricular ejection
      fraction, and increase in cardiac index were observed. However, NZ-105 showed no
      effect on heart rate and blood pressure. Based on the results mentioned above,
      cardiac hemodynamics of NZ-105 during exercise, featured primarily, reduction of
      afterload and improvement of cardiac functional deterioration due to exercise. In
      conclusion, NZ-105 is useful in patients with ischemic cardiac diseases by
      improving hemodynamics and ECG findings during exercise in patients with effort
      angina.

PMID- 8876935
TI  - Short-term clinical trial of 1-(1-[4-(3-acetylaminopropoxy)-benzoyl]-4-piperidyl)
      3, 4-dihydro-2(1H)-quinolinone in patients with diabetic nephropathy. Possible
      effectiveness of the specific vasopressin V1 receptor antagonist for reducing
      albuminuria in patients with non-insulin dependent diabetes mellitus.
AB  - We investigated the role of arginine vasopressin (AVP) in the development of
      diabetic nephropathy and the effect of specific vasopressin V1 receptor
      antagonist of 1-(1-[4-(3-acetylaminopropoxy)-benzoyl]-4-piperidyl)-3, 4-dihydro
      2(1H)-quinolinone (CAS 131631-89-5, OPC-21268) on albuminuria in patients with
      non-insulin dependent diabetes mellitus. Basal levels of AVP in diabetic patients
      showing microalbuminuria were significantly high compared to diabetics without
      any complications, suggesting that in those patients abnormally high amounts of
      AVP seem to be secreted. Three-week treatment with OPC-21268 demonstrated that
      albuminuria significantly decreased without affecting renal function. Increased
      secretion of AVP may induce proliferation of renal mesangial cells and modify
      blood flows in the glomerular capillaries. The present data suggest that OPC
      21268 may be useful for preventing the development of diabetic nephropathy,
      although its long-term effects should be examined. In conclusion, AVP may play a
      crucial role in the pathophysiology of diabetic nephropathy and that OPC-21268
      seems to prevent further progression of nephropathy in non-insulin dependent
      diabetes mellitus.

PMID- 8876937
TI  - Pharmacologic modulation of delayed-type hypersensitivity in mice.
AB  - In order to determine the mast cell requirements in murine delayed-type
      hypersensitivity (DTH), the effects of the antihistamine chlorpheniramine, the
      inhibitor of mast cell degranulation repirinast (CAS 73080-51-0, MY-5116), the
      lipoxygenase and cyclooxygenase inhibitor BW-755C (3-amino-1-[m
      (trifluoromethyl)phenyl]-2-pyrazoline), and the cyclooxygenase inhibitors
      ibuprofen, diclofenac and phenylbutazone on murine DTH reactions were examined.
      When chlorpheniramine (50 mg/kg) was administered orally immediately after, 5 h,
      or 9 h after antigen challenge, it did not show any effect on sheep red blood
      cells (SRBC)-induced delayed footpad reaction (FPR) in mice. On the other hand,
      when chlorpheniramine was administered orally 16 h after antigen challenge, it
      significantly inhibited SRBC-induced delayed FPR (p < 0.01). When repirinast (30,
      100 mg/ kg) was administered orally 16 h after antigen challenge, it
      significantly inhibited delayed FPR in a dose-dependent manner. BW-755C (50
      mg/kg) showed no significant effect on delayed FPR when it was administered 1 h,
      7 h, or 13 h after challenge. However, it significantly inhibited delayed FPR
      when it was administered 16 h after antigen challenge (p < 0.01). Ibuprofen,
      diclofenac, or phenylbutazone showed no significant effect on delayed FPR even if
      it was administered 16 h after antigen challenge. These results demonstrate that
      mast cells could be involved in DTH reactions and that histamine and leukotrienes
      may play an important role in DTH reactions in mice.

PMID- 8876936
TI  - Effect of fluvastatin or bezafibrate on the distribution of high density
      lipoprotein subpopulations in patients with familial hypercholesterolemia.
AB  - In eight patients with familial hypercholesterolemia the effects of two lipid
      reducing drugs on subpopulations of high density lipoproteins (HDL) were
      examined. After a 14-week period of diet and diet/placebo a 12-week therapy
      followed with either bezafibrate (CAS 41859-67-0) or fluvastatin (CAS 93957-55
      2). Throughout both treatments a significant decrease of total and low density
      lipoprotein (LDL)-cholesterol, apolipoprotein B and triglycerides during both
      therapies were noted as well as an insignificant increase of HDL-cholesterol
      during bezafibrate. The nondenaturating gradient gel electrophoresis is a valid
      method for the investigation of the behaviour of HDL and was therefore chosen for
      this investigation. The individual HDL pattern and HDL diameters did not change
      in these subjects. The effect on the amounts of HDL 3b and HDL 3c was
      significantly more extensive during fluvastatin (+2.4% resp. + 2.9%) as compared
      to during bezafibrate therapy (+1.7% resp. + 2.9%). The changes noted in the HDL
      subclasses are probably due to a variable lipoprotein metabolism, for example
      increased activity of lipoprotein lipase, hepatic triglyceride lipase, lecithin
      cholesterol acyltransferase and cholesterol ester transfer protein.

PMID- 8876938
TI  - Effects of dimethindene maleate on psychomotor performance in the oculodynamic
      test compared with placebo and loratadine.
AB  - The effects of dimethindene maleate (CAS 3614-69-5) on the central nervous system
      as sustained release pellets (Fenistil OAD; OAD = once a day) and sustained
      release tablets (Fenistil retard) with an immediate release fraction-were
      investigated by means of the oculodynamic test (ODT) and visual analogue scales
      and compared to loratadine (CAS 79794-75-5) and placebo. In the confirmatory part
      of the study 18 healthy volunteers were included in a single-blind, randomised, 3
      way change-over design with Fenistil OAD, loratadine, and placebo. An additional,
      fourth exploratory arm with Fenistil retard was run in 6 (out of the 18) subjects
      after completing the main part of the study. The ODT includes electro
      oculography, choice reaction task, and cardiologic parameters under workload.
      Visual analogue scales were used for subjective ratings on well-being and drug
      effects concerning wakefulness (sedation), excitation, dizziness, performance,
      effort, and dry mouth. The results show no relevant differences between either of
      the active drugs and placebo. Therefore it can be stated that after a single dose
      there is no sedating effect of dimethindene maleate compared to loratadine or
      placebo.

PMID- 8876939
TI  - Synthesis of some 2-arylpropionic acid amides as prodrugs.
AB  - The synthesis of amide prodrugs of some 2-arylpropionic acids (ibuprofen,
      naproxen, diclofenac and ketorolac) and the enantiomeric separation of these
      compounds are reported in this paper. The compounds were prepared from the
      corresponding 2-arylpropionic acids and (R-(-)-2-amino-1-butanol in the presence
      of N,N'-dicyclohexylcarbodiimide (DCC). Enantiomers were separated by preparative
      chromatography or crystallisation. The structure were confirmed by infrared,
      nuclear magnetic resonance and elementary analysis. The compounds prepared in the
      study have significant analgesic activity.

PMID- 8876940
TI  - Studies on the chronic oral toxicity of an analgesic drug combination consisting
      of acetylsalicylic acid, paracetamol and caffeine in rats including an electron
      microscopical evaluation of kidneys.
AB  - The analgesic drug combination Thomapyrin consisting of acetylsalicylic acid (CAS
      50-78-2, ASA), paracetamol (CAS 103-90-2, NAPAP) and caffeine (CAS 58-08-2) in
      the ratio 5:4:1 was investigated for its chronic toxicity in rats. For comparison
      the individual drugs ASA and NAPAP as well as the double combination ASA+NAPAP
      were tested in equipotent doses. 20 male and 20 female rats per group
      (Chbb:THOM/SPF) received doses of 50, 100 and 200 mg/kg of the combination
      ASA+NAPAP+caffeine, 45 and 180 mg/kg of the combination ASA+NAPAP, and 50 and 200
      mg/kg of the individual drugs ASA or NAPAP over a period of 6 months. The daily
      dose was splitted into two parts and administered 3 h apart. The rats were single
      housed under standardized conditions with free access to food and drinking water.
      Plasma concentrations were measured in four additional animals of all high dose
      groups after the last dosing at seven time points. Besides the usual routine
      toxicological investigations the kidneys of five females per group were
      investigated by transmission electron microscopy. All investigations were
      performed according to GLP regulations. All animals behaved unobtrusively
      throughout the study with only minor impairment of general conditions in some
      animals of all ASA, ASA+NAPAP+caffeine and the high dose NAPAP groups. Dose
      related mortality was observed in the groups receiving ASA alone or in
      combination, partly with rales and tonic convulsions immediately prior to death.
      Body weight gain was decreased in males but not in females of the ASA+NAPAP+
      caffeine and ASA groups. No consistent drug- and dose-dependent changes in
      hematological, clinico-chemical or urinanalytical parameters were observed,
      except for a slight increase in excretion of epithelial cells in both genders of
      the ASA groups. Plasma drug level monitoring demonstrated that the
      pharmacokinetics of ASA were not altered by co-administration of caffeine or
      NAPAP or vice versa. In males, maximum plasma concentrations (Cmax) and areas
      under the curve (AUC) for ASA and NAPAP tended to be slightly lower than in
      females. The plasma concentrations reached in the study represent a low multiple
      (2.2-7.9) of therapeutic plasma levels. Therefore, the results reported in the
      study can be considered representative for normal therapeutic use of the
      analgesic combination ASA+NAPAP+caffeine. Gastric erosions in the ASA and
      ASA+NAPAP+caffeine groups, increased kidney weights in females given 200 mg/kg
      ASA+NAPAP+caffeine, and dose-dependently increased liver weights in females given
      200 mg/kg ASA and decreased liver weights in males at 100 and 200 mg/kg ASA
      NAPAP+caffeine were the only consistent drug-induced changes observed at
      necropsy. Except for the above mentioned ulcer, all histopathological findings
      were iatrogenic or spontaneous lesions. The kidneys demonstrated initial stages
      of age-associated nephropathy at comparable incidence and severity in all groups
      including controls. Semi-thin section evaluation and transmission electron
      microscopy showed only minor changes. Taking all tubular and vascular changes
      together (total mean), the animals of the NAPAP group were slightly more affected
      than those of the other groups. Summing up it can be concluded that the
      nephrotoxic potential of the combination ASA+NAPAP+caffeine, if existing at all,
      was marginal even after prolonged administration, and that it does not exceed
      that of the monosubstances when given at pharmacologically equipotent doses and
      clinically relevant exposures.

PMID- 8876941
TI  - A new series of 6-chloro-2,3-dihydro-4(1H)-quinazolinone derivatives as
      antiemetic and gastrointestinal motility enhancing agents.
AB  - New 6-chloro-2,3-dihydro-4(1H)-quinazolinones (24-27) have been synthesized and
      evaluated for gastrointestinal prokinetic and antiemetic activities in comparison
      with structurally related benzamides (21-22) and 6-chloro-2,3-dihydro-(1H)-1,3
      benzoxazolin-4-ones (28). Their key pharmacophoric element has been defined as a
      6-membered ring replacing the "virtual ring" arising from the hydrogen bond
      between amidic nitrogen and methoxy group in metoclopramide (1) and structurally
      related benzamides (2-10). Variations of heterocycle linking groups have pointed
      out that a lipophilic aromatic group in position 1 plays an important role for
      pharmacological properties, while the steric restriction and the modification of
      the side-chain nucleophilicity are uneffective both for the in vitro and in vivo
      activity. Some of these compounds very effectively enhance gut peristaltic
      activity in vitro (rabbit jejunum), increase gastric emptying of a semisolid meal
      (in rats), and inhibit cisplatin-induced emesis (in pigeons), favourably
      comparing with cisapride.

PMID- 8876942
TI  - Anti-gastric acid secretory mechanism of 1,6-dihydro-2-[2-(2
      methylpropoxy)anilino]-6-oxo-5-pyrimidinecarboxylic acid. Effect on mucosal mast
      cell.
AB  - To clarify the anti-gastric acid secretory mechanism of 1,6-dihydro-2-[2-(2
      methylpropoxy)anilino]-6-oxo-5-pyrimidinecarbo xylic acid (CAS 98772-05-5, MAR
      99), the relationship between gastric acid secretion and gastric mucosal mast
      cell (MMC) was studied and the effect of this compound on these parameters was
      examined and compared with anti-allergic drugs (mast cell stabilizers) and anti
      ulcer drugs. The release of histamine from MMC cultured from bone marrow and
      connective tissue mast cell (CTMC) isolated from peritoneal cavity was found to
      be induced by the addition of ethanol (final conc. 17.5%), and the inhibitory
      effect on histamine release from MMC is closely associated with the anti-gastric
      secretory effect. That is to say, MAR-99 (10(-9)-10(-7) mol/l) inhibited
      histamine release from MMC induced by ethanol in a concentration-dependent
      manner. The action of MAR-99 on MMC was more sensitive than that of CTMC. In
      addition, MAR-99 (100 mg/kg i.d.) suppressed gastric acid secretion. On the other
      hand, anti-allergic drugs (mast cell stabilizers), such as DSCG and tranilast
      (both 10(-7) mol/l), markedly inhibited histamine release from CTMC induced by
      ethanol, but these drugs (10(-8)-10(-7) mol/l) showed only a tendency to prevent
      the release of histamine from MMC. Furthermore these drugs (both 100 mg/ kg i.d.)
      had no effects on gastric acid secretion. Equally anti-ulcer drugs, such as
      cetraxate, teprenone and sofalcone, had no effects on histamine release from mast
      cells of two types and gastric acid secretion. From these results, it was
      suggested that MMC is closely correlated with gastric acid secretion, and the
      anti-gastric secretory effect of MAR-99 may mainly contribute to prevent the
      degranulation of MMC.

PMID- 8876943
TI  - Role of nitric oxide in gastrokinetic effects of the new benzoxepine derivative
      exepanol hydrochloride.
AB  - The gastrokinetic effects of exepanol hydrochloride (rac. 3,5-cis-2,3,4,5
      tetrahydro-3-methyl-amino-1-benzoxepine-5-ol hydrochloride, CAS 77416-65-0, KC
      2450) on gastrointestinal motility were studied both in vivo and in vitro.
      Exepanol-HCl accelerated the gastrointestinal (GI) transit in vivo in mice. This
      effect of exepanol-HCl was reduced by atropine, hemicholinium-3, morphine and MCN
      A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyl trimethyl ammonium chloride). In
      guinea pig (GP) ileum, exepanol-HCl facilitated the peristaltic reflex to
      threshold pressures and restored the reflex in fatigued preparations. These
      effects of exepanol-HCl were compared with metoclopramide (MCP) which was used as
      reference compound in both in vivo and in vitro experiments. Exepanol-HCl also
      partially reversed the L-arginine induced tonic "hump' responses of GP ileum to
      transmural stimulation. These findings suggest a cholinergic involvement and a
      partial role of nitric oxide in the mechanism of action of exepantol-HCl on GI
      motility.

PMID- 8876944
TI  - Mammary excretion and placental transfer of cis-malonato[(4R,5R)-4,5
      bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II) in rats.
AB  - The mammary excretion and placental transfer of cis-malonato[(4R,5R)-4,5
      bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II) (CAS 146665-77-2, SKI
      2053R), a new potential anticancer agent, were investigated in the lactating or
      pregnant rats after a single intravenous administration of 14C-SKI 2053R (20
      mg/kg, 100 microCi/kg). The radioactivity of the milk declined in a biexponential
      fashion with an initial half-life of 0.39 h and with a terminal half-life of
      14.05 h in the lactating rats. The radioactivity of the milk was lower than that
      of plasma until 1 h after dosing, but was higher than that of plasma from 4 h
      after dosing. 14C-SKI 2053R was well distributed to most tissues including uterus
      and placenta in the pregnant rats, but the levels of radioactivity in the
      amniotic fluid and fetuses were markedly lower than that in the maternal plasma.
      Therefore, it is concluded that SKI 2053R scarcely passes the blood-placenta
      barrier, which was confirmed by the whole-body autoradiography study.

PMID- 8876945
TI  - Toxicity and enzyme-inducing effect of the antiviral compound mopyridone in mice.
AB  - Mopyridone (CAS 82822-14-8, MP) is a new antiviral compound with low acute
      toxicity in mice. Phenobarbital (PB) induction did not alter MP oral acute
      toxicity, while methylcholanthrene (MC) and dexamethasone (DEX) induction
      increased it. MP (1/10 of LD50, 5 days) increased aniline hydroxylase activity
      (by 158%) and cytochrome P-450 content (by 43%), but has no significant effect on
      liver N-demethylase activity (ethylmorphine N-demethylase, amidopyrine N
      demethylase and benzphetamine N-demethylase) in mouse liver 10,000 x g
      supernatant. The inducing effect of MP was similar to the effect of MC and
      differed from the effect of PB. The combination MP + PB exerted an additive
      inducing effect on aniline hydroxylase (by 390%) and cytochrome P-450 content (by
      183%) without affecting PB induced N-demethylases. The character of the MP + PB
      interaction was similar to that of the MC + PB interaction and suggested
      different inducing mechanisms of MP and PB. The participation of some cytochrome
      P-450 isozymes, induced by MC and DEX, in biotransformation of MP to more toxic
      product(s) was suggested.

PMID- 8876946
TI  - In vitro synergistic activity of ketoconazole with valproic acid against Candida
      species.
AB  - The susceptibility of 148 strains of Candida albicans and 20 strains of Candida
      species from patients was tested against ketoconazole (CAS 65277-42-1, KTZ),
      valproic acid (CAS 99-66-1, VPA) and the combination of KTZ and VPA, using
      Sabouraud's and YNB (yeast nitrogen base) media. Minimal inhibitory
      concentrations (MIC) with regard of C. albicans determined on diagnostic plates
      which contained Sabouraud's medium gave values of 49.84 +/- 5.83 mg/l (KTZ) and
      202.97 +/- 17.70 mg/l (VPA), and on plates which contained YNB agar, values of
      8.06 +/- 0.99 mg/l (KTZ) and 122.57 +/- 12.08 mg/l (VPA). The combination of KTZ
      and VPA in various ratios (1:1, 1:2, 2:1) was found to exert synergistic effects
      against C. albicans on Sabouraud's medium and the mean values of the combinations
      were: 4.29 +/- 0.37, 5.29 +/- 0.37, 5.02 +/- 0.38 mg/l. These results were
      significantly different (p < 0.001) compared with KTZ. The findings indicate that
      VPA, an antiepileptic drug, increases the antifungal activity of KTZ against C.
      albicans and Candida species in vitro.

PMID- 8876947
TI  - Methylotrophic yeast hansenula polymorpha as production organism for recombinant
      pharmaceuticals.
AB  - Since the onset of genetic engineering, yeasts belong to the preferred host cells
      for the production of heterologous proteins. They combine ease of genetic
      manipulation and cultivation with the ability to process and to modify the
      produced compounds according to a general eukaryotic scheme. Since yeasts do not
      contain pathogens, pyrogens or viral inclusions they constitute attractive
      production systems for proteins considered for therapeutic administration. At the
      beginning of gene technology the attention of biotechnologists focussed on the
      use of the best characterized species Saccharomyces cerevisiae. Insulin and
      hepatitis B vaccines are examples for S. cerevisiae-derived therapeutics. In
      recent years alternative yeast have become accessible for the techniques of
      modern molecular genetics and thus for potential applications in biotechnology.
      In this respect the methylotrophic yeast Hansenula polymorpha offers especially
      advantageous characteristics as host for the production of pharmaceutical
      proteins. As a consequence, production systems based on this yeast have been
      established for serum proteins, vaccines and other therapeutically important
      compounds. Some H. polymorpha-derived products are under preclinical or clinical
      trials at present and are expected to reach the market within the near future. In
      the following article the current status of this system is presented and
      discussed comparing it with other expression systems.

PMID- 8876949
TI  - Quantitative radiography in osteoarthritis: plain radiographs.
AB  - Radiological assessment of joint space width on plain radiographs is the most
      frequently used primary outcome criterion in clinical trials of disease modifying
      drugs. Changes in measurement over time are slow. Therefore, in order to improve
      the capacity of measurement to detect changes, the sources of variability (i.e.
      radiographic procedure, joint positioning, process of measurements, etc.) must be
      limited. Precise guidelines concerning radiographic procedure, joint positioning
      and methods of reading are required to achieve this goal.

PMID- 8876948
TI  - Diagnostic radiography in rheumatoid arthritis: benefits and limitations.
AB  - In the light of more modern techniques such as sonography and magnetic resonance
      imaging, the reader may well ask if plain radiography has still a role in the
      diagnostic work-up of rheumatoid arthritis. However, in daily routine, the value
      of diagnostic radiography in support of the clinical and laboratory diagnosis of
      rheumatoid arthritis is unrivaled. It allows differentiation from other joint
      diseases, such as osteoarthritis or crystal arthropathies, when the ARA criteria
      are not conclusive for the diagnosis of rheumatoid arthritis. Further, plain
      radiography is part of the basic documentation of the disease in measuring
      disease progression. Therapeutic decisions, such as systemic versus local
      therapy, and selection of drugs, as well as the form of local therapy, are
      heavily dependent on radiographs. However, the limitations of radiography in
      evaluating disease progression have to be recognized. Ultrasonography, as a
      'bedside method', and MRI are indispensable adjuncts to radiography, because they
      are superior in detecting synovitis, early forms of cartilage damage as well as
      bone reaction such as erosions and cysts. A superior assessment of the degree of
      synovial changes is also possible with MRI.

PMID- 8876950
TI  - Quantitative radiography in osteoarthritis: microfocal radiography.
AB  - Quantitative macroradiography of patients with hand and knee OA, employing
      standardized radiographic and mensural procedures, permit: accurate and
      reproducible measurements of all radiographic features. significant changes in
      JSW and osteophyte number and size to be detected within as short a period as 18
      months. therapeutic effects upon articular cartilage to be determined from
      changes in JSW. a better understanding of the disease process from an evaluation
      of the relative changes in the different radiographic features of OA.

PMID- 8876951
TI  - Quantitative radiography in osteoarthritis: analysis.
AB  - This article has reviewed the use of semiquantitative individual feature scales
      based on standard photographs in published atlases, and quantitative techniques,
      including chondrometry, high-definition microfocal radiography, and computerized
      digital image analysis, and commented on their use in longitudinal studies of
      osteoarthritis where data are obtained from the reading of serial radiographs.
      For investigators planning future studies involving the reading of already
      available radiographs, the use of computerized digital image analysis, if
      available, is recommended for measurement of joint space because of its superior
      reliability; if this is not available, then chondrometry should be used. Other
      individual features should be scored using a standard atlas. For investigators
      planning new studies, especially therapeutic trials, recent guidelines
      recommended by a World Health Organization Satellite Workshop on 'The
      standardization of methods for the assessment of articular cartilage changes in
      osteoarthritis of the knee and hip joint' should be followed (Dieppe, 1995).

PMID- 8876952
TI  - Quantitative radiography in osteoarthritis: computerized measurement of
      radiographic knee and hip joint space.
AB  - Radiographic joint space narrowing is the hallmark of progression in
      osteoarthritis (OA). An accurate measure of progression for OA requires a precise
      quantitative method. New techniques have been designed to quantitatively assess
      knee and hip joint space using computer analysis of digitally stored radiographs.
      The interobserver coefficient of variation of the technique ranges from 1% to
      3.3% and is clearly better than that obtained by the use of dividers and rule. A
      precise standardization of the radiological procedure as well as use of films of
      good quality are required for a good reproducibility of the method. The
      computerized measurement of joint space size from standard radiographs is
      applicable to monitor progression of hip and knee OA, and appears to be of value
      in the evaluation of disease-modifying therapies for OA.

PMID- 8876953
TI  - Plain X-rays in rheumatoid arthritis: overview of scoring methods, their
      reliability and applicability.
AB  - Radiographs are a suitable outcome measure in patients with rheumatoid arthritis.
      They reflect the history of the joint pathology and provide a permanent record
      necessary for serial evaluation of the disease. Great care should be taken to
      overcome technical problems with radiographs to ensure that good quality films
      are available to score. Many scoring methods have been described ranging from a
      global score for the whole patient to the more sophisticated methods of scoring
      erosions and joint space narrowing in a selected number of joints. These latter
      abnormalities give additive information and are the most important features in
      scoring radiographs in rheumatoid arthritis. An overview of the most important
      methods is given with an emphasis on four selected methods: the Larsen method, a
      modification of this by Rau and Herborn, the Sharp method and a modification of
      this by van der Heijde. All four methods produce sufficient intra- and inter
      observer reliability. Although data are scarce, the Sharp method and its
      modifications seem the most sensitive methods for detecting changes over time.
      However, these are more time-consuming than the Larsen method or its
      modifications. Depending on the type of study a choice can be made between the
      two types of methods. For clinical trials where small differences are important,
      the (modified) Sharp method seems the most appropriate. In working with large
      data sets, time might be a more crucial factor and, therefore, the (modified)
      Larsen method could be chosen.

PMID- 8876954
TI  - Radiology and spondylarthritis.
AB  - Radiographs are characteristically required to define the nature of the disease
      process in spondylarthritis. They need rarely be repeated, except for
      complications or unusual manifestations of the underlying disease. To date, new
      techniques of radio-imaging have provided only minimal advantages, if any.
      (Berkowitz et al, 1991; Docherty et al, 1992; Gibbon, 1992; Ralston et al, 1992;
      Deyo, 1994; Jensen et al, 1994). The plain radiograph is still pivotal to our
      understanding of the disease.

PMID- 8876955
TI  - Diagnostic and quantitative arthroscopy: quantitative arthroscopy.
AB  - Arthroscopy still remains the 'gold standard' for the assessment of articular
      cartilage and synovium because it provides direct and magnified evaluation of
      these anatomical structures. Thus, alongside the use of arthroscopy as a
      diagnostic or therapeutic procedure in knee disorders, a further function of knee
      arthroscopy, performed under local anaesthesia on an outpatient basis, has been
      proposed: the monitoring and follow-up of knee chondropathy and synovitis
      conducted for research purposes on patients suffering from knee osteoarthritis or
      chronic synovitis. This function is used in order (1) to evaluate the natural
      history of these diseases, (2) to assess 'de visu' the effect on chondral or
      synovial lesions of medical treatments or surgical interventions, and (3) to
      validate non-invasive imaging techniques such as plain radiographs or magnetic
      resonance imaging. The development of this arthroscopic outcome measurement of
      chondropathy and synovitis required the establishment and validation of systems
      for scoring the severity of chondral and synovial lesions. The author reviews
      both earlier and newer arthroscopic classifications and underlines the need for a
      quantitative description of cartilage and synovial abnormalities, either global
      and based on the investigator's overall assessment by using a visual analogue
      scale of severity, or, more analytically, taking into account the baseline
      parameters of the lesions, i.e. depth/intensity, extent and location.

PMID- 8876956
TI  - Diagnostic arthroscopy.
AB  - Arthroscopy has served a diagnostic role for most of this century, but found
      widespread popularity only when operative interventions were coupled with the
      procedure. The untapped potential inherent in directly observing the pathoanatomy
      underlying various rheumatologic disorders is being unlocked by developments on
      several fronts that have taken arthroscopy away from the operating room
      environment. Information from arthroscopy can influence diagnosis and treatment
      in certain non-traumatic knee disorders, particularly when the cause of synovitis
      is not evident from other clinical features and when knee symptoms are
      accompanied by bland synovial fluid and X-rays that are normal or show only
      minimal changes of osteoarthritis. Other joints can now be arthroscoped, which
      may prove useful for rheumatological diagnosis and evaluation, particularly for
      the smaller joints of the upper extremity commonly affected in 'early' disease
      states.

PMID- 8876957
TI  - Synovial fluid cell analysis.
AB  - Arthrocentesis has to be considered as a part of the clinical examination. A
      reasonable amount of aspirated synovial fluid is the best argument in favour of
      an objective articular disorder. Moreover some very simple evaluations are very
      helpful to make a diagnosis and to distinguish some particularities of rheumatic
      diseases. Such evaluations have to include both bacterial and synovial fluid
      analysis. Moreover, when performing synovial fluid analysis, a search for
      microcrystals is also performed. Haemarthrosis can easily be distinguished from a
      traumatic tap if the investigator is observing carefully the synovial fluid
      entering in the syringe. The diseases responsible for haemarthrosis differ with
      the age of patients: chondrocalcinosis, together with osteoarthrosis, is the most
      frequent aetiology in the elderly; disorders of haemostasis and synovial tumours
      are mostly observed in children and young adults. Paucicellular (< 1000
      cells/mm3) synovial fluid is observed in different 'mechanical' disorders. In the
      case of purulent synovial fluid the primary diagnosis is septic arthritis.
      However, the most common aetiology is probably crystal-induced acute arthritis.
      Differential cell count analysis performed in case of 'inflammatory' (> 1000 or
      2000 cells/mm3) synovial fluid usually shows a predominance of polymorphonuclear
      cells. However, high cellularity may sometimes be associated with a predominance
      of other cells, i.e. lymphocytes, monocytes, eosinophils. In this situation, such
      a simple evaluation (differential cell count analysis) is very helpful in making
      a diagnosis, e.g. eosinophilic arthritis, or to distinguish some particularities
      of rheumatic diseases, e.g. absence of cartilage breakdown in case of lymphocytic
      arthritis.

PMID- 8876958
TI  - Percutaneous needle biopsy and synovial histology.
AB  - Percutaneous needle biopsies of synovium are successfully used for diagnosis and
      investigation of joint disease by an increasing number of groups around the
      world. This procedure can be done in the office with little morbidity; a large
      number of samples can minimize the potential limitation of sampling error.
      Clinical indications for 'imaging the joint' by looking at morphological and
      other features of the actual tissue include undiagnosed acute or chronic mono- or
      oligoarthritis, haemarthrosis, suspected deposition diseases, new developments in
      previous stable disease and less often unexplained polyarthritis. Research into
      any joint disease can be helped by study of synovium especially using newer
      immunohistochemical, EM and molecular techniques. This report has reviewed other
      methods used for obtaining synovium, described the different percutaneous biopsy
      needles, detailed the methods used for biopsy with the Parker-Pearson needle and
      described how our group handles tissue so as to obtain maximal impact. The very
      few side effects of needle biopsy include haemarthrosis and, rarely, needle
      breakage. Finally, we have provided a brief overview of normal synovium and some
      aspects of synovium in a variety of joint diseases.

PMID- 8876959
TI  - A simple procedure for large-scale purification of 9-cis beta-carotene from
      Dunaliella bardawil.
AB  - For experiments designed to obtain reliable data on the metabolic pathway and
      biological function of 9-cis beta-carotene, sufficient quantity of this substance
      in pure form is needed. For this purpose, we decided to purify 9-cis beta
      carotene from the dry powder of the alga Dunaliella bardawil. By use of both
      silica gel and ODS open column chromatography and high-performance liquid
      chromatography (HPLC) on an ODS column and by treatment of the sample with
      ethanol, we could obtain this carotenoid as fine needle-shaped orange crystals.
      They were found to be highly pure as judged by analytical HPLC, absorption
      spectrum, and nuclear magnetic resonance analysis.

PMID- 8876960
TI  - Effects of IFN-beta and 1,25-dihydroxyvitamin D3 on cellular proliferation,
      induction of 2',5'-oligoadenylate (2-5A) synthetase and changes in immunoreactive
      pRB/p53 in human prostatic JCA-1 cells.
AB  - The combined antimitogenic effects of IFN-beta and 1,25-dihydroxyvitamin D3 (vit.
      D3) were investigated by treating the androgen-independent JCA-1 cells,
      established from the primary prostatic tumor site prior to anti-hormonal therapy,
      with IFN-beta (1000 IU/ml), vit. D3 (100 nM), and both agents. Cell growth,
      changes in overall RNA and protein contents, and cell cycle regulatory proteins
      pRB/p53 were determined. After a 24 h exposure, a significant reduction in cell
      proliferation was observed in all three conditions. IFN-beta, vit D3, and their
      combination elicited, respectively, a 1.7-, 1.6- and 2.5-fold increase in total
      RNA and a corresponding 1.4-, 1.2- and 1.7-fold increase in soluble proteins. The
      IFN-inducible 2-5A synthetase activity was elevated by 15-, 1.4- and 21-fold,
      respectively. No differences in cell cycle phase distribution were found between
      control and treated samples. However, a significant change in pRB and p53
      expression was observed upon exposure to these agents. A progressive increase in
      total pRB was observed in untreated JCA-1 cells, with the 48 h culture showing a
      1.9-fold increase over the 6 h culture. The ratio of phosphorylated to the
      nonphosphorylated forms of pRB, however, decreased from 3.00 at 6 h to 1.2 at 48
      h. The overall pRB increase as well as the modified:unmodified protein ratio
      change were both markedly decreased when the cells were treated with IFN-beta,
      vit. D3, or their combination. With p53, a similar progressive increase was also
      observed in control cells, which was largely abolished by IFN-beta but only
      partially blocked by vit. D3. The combination of IFN-beta and vit. D3 gave
      results similar to samples receiving vit. D3 alone suggesting that the effects of
      IFN-beta, insofar as p53 modulation is concerned, is distal to the effects of
      vit. D3.

PMID- 8876961
TI  - Enhancement of in vitro renaturation of recombinant human pro-urokinase by
      ampicillin.
AB  - Ampicillin was used in in vitro renaturation process of recombinant human
      prourokinase and it can obviously improve the yield of the renaturation, although
      not as well as arginine. When ampicillin was used together with arginine or
      lysine, it decreased the yield of the renaturation comparing with the yield when
      arginine or lysine used alone.

PMID- 8876962
TI  - Inhibition of estradiol-17 beta secretion in ovarian granulosa cells by an
      extract from the submandibular gland of the rat.
AB  - The submandibular salivary gland (SMG) in the rodent is a rich source of growth
      factors. The estradiol-17 beta (E2) secretions were studied in the primary
      cultures of ovarian granulosa cells from sialoadenectomized (surgical removal of
      SMG, SDX) immature rats. The secretions of luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) were also studied in the primary cultures of anterior
      pituitary cells from SDX rats. E2 secretion from the ovarian granulosa cells of
      SDX rats was not affected by male and female SMG extracts. FSH-stimulated E2
      secretion, however, was inhibited by the SMG extracts. Substances in the SMG
      extract, which inhibited FSH-stimulated E2 secretion in the cells, were heat and
      urea stable, and were not stripped by charcoal. SMG extracts did not affect the
      secretions of LH and FSH in the anterior pituitary cells, with or without
      luteinizing hormone-releasing hormone. The present findings suggest that male and
      female rat SMG contain the E2 modulating factor which affect ovarian granulosa
      cells.

PMID- 8876963
TI  - Translation initiation region plays an important role in the expression of human
      thrombopoietin in Escherichia coli.
AB  - A mutant human thrombopoietin (TPO) gene with a modified translation initiation
      region (TIR) sequence was created by site-specific mutagenesis based on the PCR
      technique. This mutant TPO gene encoded the same amino acid sequence as wild-type
      TPO gene. The wild-type TPO gene was expressed in E. coli with very low
      efficiency. The mutant TPO gene could reach an expression level of up to 10% of
      total cellular proteins in E. coli, which was much higher than the wild-type
      gene. The recombinant protein was mainly in the form of inclusion body which
      could acquire in vitro activities of human thrombopoietin after refolding.

PMID- 8876964
TI  - Identification of a cAMP-dependent protein-DNA interaction at a sequence near the
      yeast mitochondrial rRNA genes.
AB  - We have shown that expression of yeast mitochondrial (mt) rRNA genes (S.
      cerevisiae) is controlled in a cAMP-dependent manner via PKA, suggesting a trans
      activation process involving phosphorylation-dependent protein-mt DNA
      interaction. We used filter-binding assays, mt protein extracts, and mt DNA from
      a rho-mutant strain retaining the 21S rRNA gene to demonstrate such an
      interaction. Competition assays with the cloned 21S-related mt DNA fragment
      undergoing interaction showed that a sequence in that fragment is present in mt
      DNA from a rho-strain retaining the 16S mt rRNA gene, but not in a VAR1-retaining
      rho-strain that lacks cAMP-mediated mt transcription. The sequence of the 21S
      related mt DNA fragment undergoing protein interaction includes a GC cluster;
      that GC cluster sequence is also present near the 16S gene but not near VAR1.
      These and other data are consistent with a role for the GC cluster in cAMP
      mediated expression of mt rRNA genes.

PMID- 8876965
TI  - Indole-3-carbinol as a scavenger of free radicals.
AB  - The ability of indole-3-carbinol (indole-3-methanol) to trap a metastable
      synthetic-free radical is presented. Indole-3-carbinol is capable of acting as a
      scavenger of free radicals in an in vitro system. The presence of indole-3
      carbinol determines the disappearance of the free radicals, the reaction being
      time- and concentration-dependent. The scavenging activity of different indoles
      is compared. Indole-3-carbinol and indole-3-acetic acid are both able to scavenge
      free radicals, but indole-3-carbinol is more effective. Other indoles such as
      indole-3-aldehyde and indole-3-carboxylic acid do not show the ability to trap
      free radicals. Indole-3-aldehyde appears as a product of indole-3-carbinol
      reaction with free radicals. The formation of an adduct between the free radical
      generated in vitro and indole-3-carbinol has also been detected. Stability of
      indole-3-carbinol in buffered media at different pH values and formation of 3,3'
      diindolylmethane from indole-3-carbinol is also studied. The scavenging activity
      of indole-3-carbinol and its implications on the anti-carcinogenesis process is
      discussed.

PMID- 8876966
TI  - Coenzyme Q depletion in rat plasma after partial hepatectomy.
AB  - Coenzyme Q content was monitored in blood plasma and regenerating liver
      mitochondria of hepatectomized rats, using as controls either sham-operated or
      non-operated animals. Mitochondrial CoQ9 content increased in sham-operated rats,
      whilst it was significantly lower in hepatectomized in comparison with non
      operated animals at all considered times. On the other hand plasma CoQ9 levels
      dramatically decreased in hepatectomized animals, while strongly increased in
      sham-operated in comparison with non-operated rats. The quinone decrease in
      hepatectomized animals is likely to be due to the attainment of a rate-limiting
      step in CoQ biosynthesis.

PMID- 8876967
TI  - Organization and nucleotide sequence of genes for hemagglutinin components of
      Clostridium botulinum type B progenitor toxin.
AB  - The genes for hemagglutinin components (33 kD, 17 kD, and 21.5 kD) of Clostridium
      botulinum type B progenitor toxin were cloned and sequenced. Analysis of the
      nucleotide sequence showed that the 33 kD, 17 kD, and 21.5 kD hemagglutinin genes
      were organized into an operon in the 5'upstream region of the toxin gene and
      their ORF orientation were opposite to that of the toxin gene. A comparison of
      amino acid sequences between the hemagglutinin components in type B and type C
      progenitor toxin showed significant homology. Northern blot analysis also
      revealed that all of the genes for the hemagglutinin components were transcribed
      as a polycistronic RNA.

PMID- 8876968
TI  - Purification of pepsinogens from human urine and electrophoretic analysis by
      caseogram print.
AB  - Pepsinogen (PG) A and C were purified from human urine, and analyzed by a highly
      sensitive detection method, "caseogram print". Purification was achieved by a
      series of conventional chromatographies and FPLC. A relatively large amount (13.2
      mg) of PGA was purified from about 20 liters of urine. Purified PGA was separated
      by a Mono-Q column into each of its isozymogens. The elution order (PGA-5, 4+3,
      2) corresponded to the order of electrophoretic migration. Although the
      concentration of urinary PGC was very low, a trace amount was purified and
      visualized by electrophoresis. The urinary and mucosal PGCs migrated at the same
      position, and urinary PGC was detected as two isozymogens similarly to mucosal
      PGC, suggesting that urinary and mucosal PGCs may be essentially identical.

PMID- 8876969
TI  - Purification of an alpha,beta-ketoalkene double bond reductase from Salmonella
      typhimurium.
AB  - An alpha, beta-ketoalkene double bond reductase was purified from the cell-free
      extract of Salmonella typhimurium. The purified enzyme was homogeneous by the
      criterion of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      molecular weight of the enzyme was estimated to be 24,700 by the electrophoresis
      and 23,900 by HPLC gel filtration, respectively. The isoelectric point is pH 7.2.
      The enzyme in the presence of NAD(P)H exhibited double bond reductase activity
      toward alpha, beta-ketoalkenes such as trans-phenyl-1-propenyl ketone, trans
      benzylideneacetophenone and 15-ketoprostaglandins. The enzyme activity was
      markedly inhibited by dicumarol.

PMID- 8876970
TI  - The specificity of the neuroendocrine convertase PC3 is determined by residues
      NH2- and COOH-terminal to the cleavage site.
AB  - The Kex2-like convertase PC3 (PC1) has been implicated in the processing of a
      number of prohormones and proneuropeptides. In order to be able to more
      accurately predict substrates for PC3 its specificity was defined using
      recombinant proalbumins and synthetic peptide substrates. P2P1 and P4P1 dibasic
      sites were cleaved with similar efficiencies however there were specific
      restrictions on amino acids NH2- and COOH-terminal to the cleavage site. His was
      disallowed at P2 and basic residues were forbidden at P1. The presence of a
      charged residue at P2 either completely prevented (Arg) or seriously impaired
      (Glu) cleavage by PC3 and the presence of a P4 Arg did not significantly increase
      its activity.

PMID- 8876971
TI  - Cytochrome P-450 and free radical generation in rat liver microsomes under the
      influence of prostaglandin E1.
AB  - There is evidence to suggest that the mechanism of antioxidant effect of
      prostaglandin E1 (PGE1) is due to decrease of radical species generation by
      cytochrome P-450 in rat liver microsomes. Chronic alcohol intoxication increased
      NADPH oxidation, cytochrome P-450 content and NADPH-stimulated chemoluminiscence
      of microsomes. Ethanol also raised superoxide dismutase (SOD) activity in
      microsomes. PGE1 decreased cytochrome P-450 content, normalized NADPH oxidation,
      NADPH-induced chemoluminiscence and SOD activity in the liver of alcohol-treated
      rats. PGE developed the similar effect after microsomal induction by both acetone
      combined with starvation and phenobarbital normalizing all the above parameters.
      Therefore, PGE1 affects on both, ethanol-inducible IIE1 and phenobarbital
      inducible IIB1 isoforms.

PMID- 8876972
TI  - Asporogenic Bacillus megaterium mutant 27-36 degrades intrinsically short-lived
      proteins but fails to convert most of other proteins to a short-lived fraction.
AB  - Asporogenic mutant blocked in the 0-II sporulation stage degraded pulse-labelled
      proteins in the sporulation medium at the same rate as the parental strain for
      the first two hours. The degraded fraction was mostly composed of intrinsically
      short-lived proteins which were degraded even after enriching the medium with
      amino acids and growth resumption. Proteins accessible to degradation because of
      nutritional shift down formed a lesser proportion of this fraction. The
      acceleration of protein turnover in the parent strain during the irreversible
      sporulation phase was not developed in the mutant. A first order kinetic model of
      protein degradation was used for parameter estimation. Ca(2+)-dependent
      intracellular serine proteinase was synthesized in an inactive form, which was
      activated by increasing Ca2+ concentration to 30 mM.

PMID- 8876973
TI  - ATP-induced calcium mobilization in glomerular mesangial cells is mediated by P2U
      purinoceptor.
AB  - To identify the functional P2 purinoceptor subtype in glomerular mesangial cells
      (GMC), polymerase chain reaction coupled with reverse transcription (RT-PCR) were
      performed, and cytosolic free calcium concentration ([Ca2+]i) was determined. RT
      PCR analysis revealed that the molecular identity of P2 purinoceptor localized to
      GMC was both P2U and P2Y. The rank order of potency in stimulating [Ca2+]i was
      ATP [symbol: see text] UTP > 2-methylthio-ATP > ADP [symbol: see text] adenosine
      [symbol: see text] AMP. In addition, cross-desensitization between ATP and UTP
      occurred. In conclusion, ATP induces increase in [Ca2+]i via P2U purinoceptor in
      GMC.

PMID- 8876974
TI  - Oxidized low density lipoprotein induces activation of the transcription factor
      NF kappa B in fibroblasts, endothelial and smooth muscle cells.
AB  - The effect of cupric ions or endothelial cell-oxidized LDL on the transcription
      factor NF kappa B activation was investigated by electrophoretic mobility shift
      assay. Oxidized LDL induced NF kappa B activation in fibroblasts, endothelial and
      smooth muscle cells. The extent of NF kappa B activation was proportional to the
      degree of LDL oxidation, as assessed by the lipid peroxidation product and the
      conjugated diene level. A similar activation was observed with the lipid extract
      of copper-oxidized LDL, which indicates that lipid peroxidation products are
      involved in the activation mechanism. Furthermore, alpha-tocopherol, a lipophilic
      free radical scavenger, partially inhibited the stimulatory effect of Cu(2+)
      oxidized LDL. Since NF kappa B is considered as an oxidative stress-responsive
      transcription factor, our study supports the evidence that the stress induced by
      oxidized LDL causes NF kappa B activation in different cell types, and that this
      effect can be ascribed to the lipid peroxidation products.

PMID- 8876975
TI  - Organization and nucleotide sequences of ten ribosomal protein genes from the
      region equivalent to the S10 operon in the archaebacterium, Halobacterium
      halobium.
AB  - A determination was made of the nucleotide sequence of the 7340-bp region of a
      ribosomal protein gene cluster of Halobacterium halobium, which is equivalent to
      the S10 operon of Escherichia coli. The sequence was analyzed with the
      codonpreference program deduced from the halobacterial codon usage table that
      showed a very high GC content of the third codon position. The sequence was
      comprised of a string of 13 tightly linked ORFs. Most of the ORFs were homologous
      with ribosomal protein genes (ORF1-ORF2-rpl3-rpl4-rpl23--rpl2- rps19-rpl22-rps3
      rpl29-ORF11-rps17-r pl14). The 13-gene string was preceded by three putative AT
      rich promoter sequences. The order of the genes in H. halobium essentially agreed
      with that of the corresponding genes of E. coli (S10-operon), except for certain
      deletions or insertions of additional protein genes.

PMID- 8876976
TI  - Specific guanylation of Lupinus luteus 5S rRNA at its 3' end in HeLa cell
      extract.
AB  - We have found that Lupinus luteus 5S ribosomal RNA is post-transcriptionally
      modified at its 3' end by addition of pG catalysed by HeLa cells extract. This
      extra nucleotide is not encoded within Lupinus luteus 5S rRNA gene. A similar
      reaction has been previously observed for eukaryotic histidine tRNAs. However an
      additional guanosine residue was ligated post-transcriptionally at the 5' end of
      that tRNA.

PMID- 8876977
TI  - Streptozotocin at low doses induces apoptosis and at high doses causes necrosis
      in a murine pancreatic beta cell line, INS-1.
AB  - The ability of beta cells to endure assaults by various environmental agents,
      including toxins and viruses, may be relevant to the development of diabetes. We
      have examined the mode of cell death caused by streptozotocin (STZ) in a murine
      pancreatic beta cell line, INS-1. Apoptosis was identified by detection of
      initial endonuclease-mediated DNA strand breaks by DNA gel electrophoresis.
      Apoptosis and necrosis were distinguished morphologically by light and electron
      microscopy. Higher rates of apoptosis, as compared to necrosis, were observed
      when cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery
      period. Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22%) as
      well as apoptosis (17%). These results suggest that the cytotoxic effect of STZ,
      at low doses, on beta cells involves the activation of the apoptotic pathway,
      whereas, at high doses, the mode of beta cell death is predominantly necrosis.

PMID- 8876978
TI  - Mitogenic activity of peptides related to the sequence of human fibroblast growth
      factor-1.
AB  - Linear synthetic peptides related to the human Fibroblast Growth Factor-1 (hFGF
      1) segment [112-147] were tested for their capacity of mimicking FGF mitogenic
      activity, binding to heparin-Sepharose columns, stimulating DNA synthesis and
      competing with hFGF-1 for the cellular receptors. The results obtained indicated
      that the activity of these compounds is dependent on the presence of the sequence
      WFVGLK in their structures. The affinity for the cellular receptors increased
      when this sequence was elongated in order to incorporate amino acid residues that
      are important for FGF-heparin binding.

PMID- 8876979
TI  - Studies on receptor binding site of insulin: the hydrophobic B12Val can be
      substituted by hydrophilic thr.
AB  - [B12Thr]human insulin and [B12Leu]human insulin were obtained by means of site
      directed random mutagenesis. [B12Thr]human insulin retain total biological
      activity but [B12Leu]human insulin has much lower biological activity. Receptor
      binding activities of [B12Thr]human insulin and [B12Leu]human insulin are 56% and
      3%, respectively, as that of native porcine insulin. The results suggest that the
      hydrophobic property of the residue side chain at B12 may not be necessary.

PMID- 8876980
TI  - Pb2+ and Hg2+ binding to alpha-lactalbumin.
AB  - Interactions of human alpha-lactalbumin with Pb2+ and Hg2+ were studied by
      intrinsic protein fluorescence. Lead ions bind to the strong Ca2+ binding site of
      alpha-lactalbumin (association constant Kass approximately 2 x 10(6) M-1) with
      concomitant spectral changes which are similar to those induced by the binding of
      Ca2+. Pb2+ also binds to the strong Zn2+ site with Kass approximately 10(5) M-1
      and some secondary binding site(s) (which probably contain histidine residues)
      with apparent Kass approximately 10(4) M-1, causing pronounced aggregation of the
      protein. Mercury ions bind to alpha-lactalbumin at the primary Zn2+ sites with
      Kass approximately (1-4) x 10(4) M-1, although the stoichiometry of the binding
      depends on the conformational state of the protein. Secondary Hg2+ binding sites
      were suggested to contain histidines, while the strong Hg2+ site contains
      carboxylates in the coordination sphere and seems to coincide with the strong
      Zn2+ site. The binding of both Pb2+ and Hg2+ decreases the thermal stability of
      the Ca(2+)-loaded protein and in some conditions causes pronounced protein
      aggregation.

PMID- 8876981
TI  - Inhibition of mitochondrial cytochrome C oxidase by dicarbanonaborates.
AB  - Dicarbanonaborates inhibit the mitochondrial cytochrome c oxidase activity. In
      contrast to mitochondrial ATPase or glycerol phosphate dehydrogenase, inhibition
      of cytochrome c oxidase was not competitive and the residual, drug-insensitive
      activity was higher. These results indicate that dicarbanonaborates inhibit
      various mitochondrial membrane-bound enzymes through different mechanisms.

PMID- 8876982
TI  - The selective GABAB antagonist CGP-35348 blocks spike-wave bursts in the
      cholesterol synthesis rat absence epilepsy model.
AB  - Slow IPSPs, which are believed to be involved in generation of the wave of spike
      wave epileptiform discharges, are mediated by the GABAB receptor. We therefore
      examined the effect of the GABAB antagonist, Ciba Geigy Product, CGP-35348, in
      the cholesterol synthesis inhibitor model of absence epilepsy in rat. Rats
      received Ayerst-9944 (AY-9944), from 6-45 mg i.p. in the first few weeks of life.
      By 2 months after AY-9944 administration these rats exhibited recurrent spike
      waves and behavioral arrests. In 10 such animals CGP-35348 was administered
      intraperitoneally in doses of 0 (vehicle), 10, 25 or 100 mg/kg. EEG recordings
      were obtained via previously implanted bone screws. Technologists blinded to
      treatment group counted spike-waves over a 4 h period post-injection. The average
      number of spike-wave burst seconds per 4 h of recording for all dosages and times
      was 52.4 +/- 81.4 (mean +/- S.D.) s. Mean burst times (seconds) were vehicle =
      93.5 +/- 106.5; 10 mg/kg = 69.9 +/- 79.7; 25 mg/kg = 30.8 +/- 46.9; 100 mg/kg =
      15.2 +/- 54, a mean 84% reduction at 100 mg/kg (ANOVA regression significant at
      0.0001). Spike-waves were suppressed for at least 4 h after injection of CGP
      35348. These findings supplement similar findings in other absence models, and
      support a potential role for GABAB antagonists in treatment of absence seizures.

PMID- 8876983
TI  - DNA fragmentation and nuclear endonuclease activity in rat brain after severe
      closed head injury.
AB  - Previous studies have suggested that brain cells undergo apoptotic cell death
      during several neurodegenerative disorders such as Alzheimer's disease,
      Parkinsonism and ischemic stroke. In the present study, apoptotic DNA
      fragmentation and activation of nuclear endonuclease were evaluated in rat brain
      cells after head trauma. Severe closed head injury was induced in rats by the
      impact of a 450-g weight dropped from a height of 2 m. A 12% mortality was
      experienced after head trauma. Brain cell nuclei and DNA were isolated at
      intervals of 3, 10, 24 h, 3 and 10 days after head trauma. DNA fragmentation was
      measured by the random oligonucleotide-primed synthesis (ROPS) assay and was
      significantly increased with the maximum level of DNA fragmentation occurring at
      10 h after trauma. The DNA and nuclei yields decreased 10 h after injury and
      remained at a reduced level at all subsequent sampling intervals. The DNA
      fragmentation induced after severe head trauma was accompanied by an increase in
      the activity of the Ca/Mg-dependent endonuclease associated with apoptosis. These
      data indicate that severe head injury is associated with significant brain cell
      death by apoptosis.

PMID- 8876984
TI  - Dopamine D2, receptor-mediated modulation of the GABAergic inhibition of
      substantia nigra pars reticulata neurons.
AB  - Neurons of the substantia nigra pars reticulata can be readily and fully
      inhibited by endogenously released or iontophoretically applied GABA. We have
      previously shown that co-application of dopamine or the D2-like agonist
      quinpirole causes a current-dependent attenuation of the inhibitory response of
      these neurons to GABA. To determine if the modulation of GABA responsiveness was
      mediated by activation of D2 receptors, effects of iontophoretic quinpirole were
      examined after various treatments which block or inactivate D2 receptors, or
      uncouple D2 receptors from their G-proteins. Results showed that the GABA
      attenuating effect of quinpirole could be attributed to stimulation of D2
      receptors, and not a non-specific effect of the drug, since (1) co-iontophoresis
      of the D2 antagonist YM 09151-2 antagonized the GABA-modulatory effect of
      quinpirole, (2) prior intranigral injection of the receptor inactivator N-ethoxy
      carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 50 nmol/0.5 ml one day before
      recording) prevented the response to quinpirole, and (3) prior intranigral
      injection of the Gi-Go-protein inactivator pertussis toxin (1 mg/ml 0.9% NaCl 24
      h before recording) completely abolished the ability of quinpirole to lessen the
      inhibitory response to GABA. The location of the involved D2 receptors was
      examined using selective lesioning approaches. Kainic acid lesions of the
      striatonigral pathway did not prevent the ability of quinpirole to attenuate
      responses of pars reticulata neurons to GABA. Similarly, in previous studies
      [59], 6-hydroxydopamine lesions of the adjacent pars compacta dopamine neurons
      were found not to abolish the GABA-attenuating effect of dopamine. Thus, it
      appears that the receptors mediating the response are not localized to either
      striatonigral terminals nor to the adjacent dopamine neurons, leaving open the
      possibility that the response is mediated by D2 receptors located on pars
      reticulata neurons. Collectively these results suggest that dendritically
      released dopamine may act via nigral D2 receptors, perhaps located on pars
      reticulata neurons themselves, to regulate basal ganglia output from the
      substantia nigra.

PMID- 8876985
TI  - Rapid eye movement (REM) sleep deprivation in 6-OHDA nigro-striatal lesioned rats
      with and without transplants of dissociated chromaffin cells.
AB  - Since both REM sleep deprivation and unilateral 6-OHDA lesions induce
      supersensitivity of DA receptors, the purpose of this study was to determine
      whether the response of rats with such lesions would be modified by REM sleep
      deprivation. In addition, the effect of grafts of dissociated chromaffin cells
      was also tested. Rats with 6-OHDA lesions were subjected to 24 or 72 h of REM
      sleep deprivation and tested with various doses of apomorphine to determine
      turning behavior frequencies. At end of those experiments, the animals were
      transplanted with dissociated chromaffin cells and turning behavior was tested
      again. The results showed that REM sleep deprivation nearly doubled the turning
      behavior frequency, that chromaffin cell grafts decreased it, but that REM
      deprivation in grafted animals still seemed to produce an increase of post
      synaptic supersensitivity independent of denervation. The results were discussed
      in terms of the possible relationship of sleep with Parkinson's disease through
      the DA system.

PMID- 8876986
TI  - Calcium homeostasis in cultured embryonic rat septohippocampal neurons is altered
      by ethanol and nerve growth factor before and during depolarization.
AB  - Ethanol and nerve growth factor (NGF) affect the survival of septohippocampal
      (SH) neurons. The effect of ethanol and NGF on calcium (Ca2+) homeostasis in
      these neurons was investigated in this study. Changes in intracellular-free Ca2+
      concentration ([Ca2+]i) were measured using indo-1 in cultured embryonic (E21) SH
      neurons before stimulation (basal) and during stimulation with 30 mM potassium
      cloride (KCl+). SH neurons were treated with 0, 100, 200, 400, or 800 mg% ethanol
      with NGF (+NGF) or without NGF (-NGF). NGF treatment decreased, while ethanol did
      not affect basal [Ca2+]i. The combination of ethanol and NGF treatment led to
      increases in basal [Ca2+]i. While [Ca2+]i was lower during stimulation with KCl+
      following ethanol or NGF treatment, ethanol and NGF treatment together led to
      significantly greater increases or decreases in [Ca2+]i compared to similarly
      treated NGF neurons. Responses of SH neurons were compared to those of medial
      septal (MS) neurons. Changes in [Ca2+]i during treatment with ethanol and/or NGF
      were reduced in SH neurons compared with MS neurons. We conclude that changes in
      Ca2+ homeostasis can occur in SH neurons in the presence of ethanol and/or NGF.
      The changes following ethanol treatment are enhanced by NGF. By altering Ca2+
      homeostasis, NGF may enhance the survival of SH neurons during ethanol-induced
      neurotoxicity.

PMID- 8876987
TI  - Changes in apomorphine pharmacodynamics following repeated treatment in 6
      hydroxydopamine-lesioned rats.
AB  - Rats with 6-OHDA lesions were repeatedly treated with apomorphine and dose
      response relationships compared before and after treatment to better understand
      the pharmacological mechanisms which result in sensitization. A progressive
      increase in the magnitude and duration of rotational behavior was observed
      following repeated treatment and was associated with a nonparallel (upward) shift
      in apomorphine dose-response curves. These changes are inconsistent with simple
      shifts in drug potency, and instead are more consistent with changes in the
      ability of apomorphine to stimulate postsynaptic, striatal efferent pathways
      which result from repeated drug administration.

PMID- 8876988
TI  - Diazoxide and cyclothiazide convert AMPA-induced dark cell degeneration of
      Purkinje cells to edematous damage in the cerebellar slice.
AB  - Using the in vitro cerebellar slice preparation from young rats (8-12 days old),
      AMPA produced in addition to dark cell degeneration (DCD), an edematous type of
      toxicity (edematous damage; ED) in a minority (35%) of Purkinje cells. The intent
      of this study was to evaluate whether AMPA receptor desensitization is a primary
      factor that governs the type of toxicity induced by AMPA in the in vitro
      cerebellar slice preparation. Both the competitive and noncompetitive AMPA
      antagonists CNQX and GYKI 52466, respectively, blocked ED when given during the
      entire protocol (30 min AMPA exposure followed by 90 min of recovery).
      Cyclothiazide (100 microM) and diazoxide (500 microM), two antagonists of AMPA
      receptor desensitization reversed DCD and unveiled a fulminating ED. Lowering Na+
      and lowering Cl- proved effective in blocking ED, whereas removal of Ca2+ proved
      to be ineffective. Kainate (KA) (30-100 microM) produced only 50% as much ED as
      AMPA. This study indicates that AMPA can elicit more than one type of
      degeneration in the same neuronal population and that a primary governing factor
      in determining which toxicity is expressed seems to be the ability of AMPA
      receptors to desensitize.

PMID- 8876989
TI  - Do nitric oxide synthase, NMDA receptor subunit R1 and cytochrome oxidase co
      localize in the rat central nervous system?
AB  - The activation of nitric oxide synthase (NOS) has been linked to excitatory input
      via NMDA receptors. We hypothesized that NOS-positive neurons that have NMDA
      receptors on their surface would have high levels of cytochrome oxidase (C.O.) as
      energy generator for membrane repolarization. In order to compare the
      distribution of these markers on the same section, we reacted rat brain sections
      for C.O. histochemistry followed by NOS immunogold silver staining (IGSS).
      Adjacent sections were reacted for NOS IGSS followed by indirect immunoperoxidase
      for NMDA receptor subunit R1 (NMDAR1). We found that the staining pattern varied
      among regions but were consistent within each region examined. There are three
      types of NOS immunoreactive (NOS-ir) cells: (1) NOS-ir neurons that had moderate
      to high levels of both NMDAR1 and C.O. staining, such as the pontine reticular
      nuclei, motor and mesencephalic nuclei of the trigeminal nerve, and some motor
      neurons in the spinal cord. (2) NOS-ir neurons that were immunoreactive for
      NMDAR1 (NMDAR1-ir) but had low levels of C.O. activity in thei- somata. Their
      dendrites, however, were both NMDAR1-ir and rich in C.O. Examples of this type
      include neurons in the caudate and putamen, and periglomerular cells in the
      olfactory bulb. (3) We also found that some NOS-ir neurons were not NMDAR1-ir and
      had low C.O. activity. In addition to postsynaptic neurons, C.O. and NOS levels
      were both high in the inner segments of retinal photoreceptor cells where energy
      demanding active ion transport maintains the dark current and where NO presumably
      activates guanylate cyclase for the production of cGMP, which keeps the Na+
      channels open in the dark. Our findings suggest that NMDA receptors are available
      for the majority of NOS-ir neurons, which comprise a heterogenous population with
      varying energy demands.

PMID- 8876990
TI  - The alteration of glucocorticoid receptor-immunoreactivity in the rat forebrain
      following short-term and long-term adrenalectomy.
AB  - To examine the effect of short-term and long-term adrenalectomy (ADX) on the
      glucocorticoid receptor (GR) expression, we performed an immunohistochemical
      study on the rat forebrain. One day after ADX, the GR-immunoreactivity
      significantly decreased or disappeared in most forebrain structures, while
      relatively strong GR-immunoreactivity was still found within the hypothalamus
      especially in the arcuate nucleus (ARC) and the parvocellular paraventricular
      nucleus (PVN). Two weeks following ADX, GR-immunoreactive cells disappeared in
      many structures of the forebrain including most parts of hypothalamus while
      moderate GR-immunoreactivity was still observable in the ARC and PVN. More than 3
      months after ADX, the rats still survived when they received replacement of
      corticosterone during the first 2 weeks following the operation. Moderate GR
      immunoreactivity in the ARC and PVN of the hypothalamus was exhibited whereas no
      immunoreactive cells remained in the cerebral cortex, thalamus and other
      forebrain structures when these animals showed obvious cell death in the granule
      cells of the dentate gyrus, identified with the silver impregnation method for
      degenerating cells. Massive cell loss in this hippocampal region is an indicator
      of a complete ADX, in addition to the blood corticosterone level. These results
      demonstrate topographic differences of GR expression in the rat forebrain after
      ADX with only continuous immunoreactivity in the ARC and PVN of the hypothalamus,
      suggesting that some neurons in the ARC and PVN could keep active GR probably in
      order to maintain their survival after removing the adrenal gland.

PMID- 8876991
TI  - Weight loss in rats treated with intracerebroventricular cobalt protoporphyrin is
      not specific to the neuropeptide Y system.
AB  - Cobalt protoporphyrin (CoPP) reduces food intake and body weight following
      intracerebroventricular (i.c.v.) administration in rats. We injected 0.2 mumol
      CoPP per kg body weight i.c.v. and monitored body weight and daily food intake
      for 7 days. The body weight and 24 h food intake of CoPP-treated animals was
      significantly lower than that of vehicle-treated animals in all studies (P <
      0.01) from day 2 to day 7. The 2 h feeding response (CoPP vs. vehicle-treated) to
      10 micrograms neuropeptide Y (NPY) (4.0 vs. 7.1 g; P < 0.05), the 1 h feeding
      response to 10 micrograms galanin (1.3 vs. 3.2 g; P < 0.05) and 30 micrograms
      norepinephrine (0.6 vs. 1.9 g; P < 0.05) in CoPP-treated animals were all reduced
      compared to the vehicle-treated group. In addition there was no change in
      hypothalamic NPY mRNA in CoPP-treated animals. I.c.v. CoPP decreases sensitivity
      to exogenous NPY, galanin and norepinephrine. The effect of CoPP is not specific
      to NPY as previously described.

PMID- 8876992
TI  - Dynamics of ethanol-induced transmitter packet release in the frog neuromuscular
      junction.
AB  - Intervals of spontaneous miniature endplate potentials (MEPPs) are usually
      thought to follow random kinetics because number vs. interval size plots can fit
      a Poisson distribution such that the largest number of intervals are found in the
      smallest interval bin. Even though several studies report that MEPPs have a
      tendency to clump together, an alternative dynamic has not gained acceptance. We
      found that spontaneous MEPP interval plots with commonly used bin sizes (10 ms or
      larger) from muscle fibers of diameters usually studied (20 microns) also skew to
      the smallest interval bin. In order to study very small junctions which do not
      generate enough intervals for a detailed analysis of high resolving power (small
      bin width) at normal frequencies of 0.05 MEPPs/s we increased MEPP frequencies
      with ethanol to obtain large samples. Ethanol accentuated the normal clustering
      of MEPPs and number vs. interval plots of 0.5 ms show periodic peaks at 400 Hz. A
      periodogram of power vs. frequency also showed a preferred frequency of 400 Hz.
      The first peak indicates a refractory period and the 400 Hz oscillation
      demonstrates that MEPPs are not independent. A release channel with a rhythmical
      nature is discussed as a possible molecular process which generates clusters of
      MEPPs.

PMID- 8876993
TI  - A lateral hypothalamic D1 dopaminergic mechanism in conditioned taste aversion.
AB  - The aim of this study was to elucidate the role of the neuropil located in the
      LHA in the acquisition of the association between a taste (conditioned stimulus =
      saccharin) and a visceral distress (unconditioned stimulus = lithium chloride)
      leading to long delayed learning of a conditioned taste aversion (CTA). In 82
      male rats guide-cannulae were directed bilaterally into the basolateral LHA where
      bilateral microinjections were made after the conditioned stimulus and before the
      unconditioned stimulus. We found that: (1) tetrodotoxin, a non-specific blocker
      of neuronal activity disrupted the acquisition of the CTA; (2) SCH 23390, a
      specific D1 receptor blocker also disrupted learning of the CTA, while sulpiride,
      a D2 receptor blocker, did not; (3) neither the specific blockade of D1 nor of D2
      receptors could prevent the visceral distress-induced decrease in water intake,
      showing that the visceral distress was actually experienced; and (4) the sham
      taste aversion learning (i.e. without visceral distress) revealed that neither
      the D1 nor the D2 receptors blockade induced by themselves either a taste
      preference or a taste aversion towards saccharin, indicating that the impaired
      acquisition of the CTA was not due to a superimposed taste preference that could
      have been induced by the intra-LHA D1 receptors blockade. It is concluded that
      the neuropil in the LHA is necessary in the process of the acquisition of long
      delayed learning and that it uses a D1 receptor specific mechanism.

PMID- 8876994
TI  - Developmental and stimulus-specific expression of the immediate-early gene zif268
      in rat spinal cord.
AB  - Expression of the cellular immediate-early gene, zif268, was investigated using
      immunocytochemical methods in cervical spinal cord of neonatal and adult rats.
      The postnatal expression of zif268 follows a specific temporal and spatial
      sequence in the spinal dorsal horn. Neurons immunoreactive for Zif268 protein
      were not present in cervical spinal cord before postnatal day (P) 6. At P6 they
      were occasionally observed in Rexed's lamina 1. By P11, a few additional, faintly
      labeled, Zif268-positive neurons appeared in lamina III Around P16, however, many
      immunoreactive neurons were found in laminae I-III and a few in laminae IV-VII.
      The number of Zif268-immunoreactive neurons decreased markedly by P21 and was
      further reduced by P26 to become virtually absent in adult rats. In adults,
      surgical exposure of peripheral nerves alone enhanced Zif268 expression, but this
      effect largely disappeared in less than 6 h. Electrical stimulation of the nerves
      with high-frequency long trains, typical of those known to elicit long-term
      neural plasticity, induced a marked increase in Zif268 expression in the dorsal
      horn. Stimulation with single pulses had a much weaker effect, Zif268 may thus
      play a role in stimulus-induced, long-term neural plasticity in the spinal cord.

PMID- 8876995
TI  - Non-invasive imaging of neuronal population dynamics in human thalamus.
AB  - Waveforms for early thalamic and cortical population responses to unilateral
      median nerve stimulation at the wrist were determined non-invasively for six
      subjects from 122-channel magnetoencephalographic data. Biphasic responses in
      contralateral ventral thalamus were obtained in 9 hemispheres similar to depth
      electrode results reported for patients. Thalamic responses occurred at 15.1-17.4
      and at 19.2-24 ms. Responses in contralateral sensorimotor cortex began at 16.3
      18.8 ms.

PMID- 8876996
TI  - Immunoelectron microscopic study on neuropeptide Y in the periodontal ligament of
      the incisor following peripheral nerve injury to the inferior alveolar nerve in
      the rat.
AB  - Immunoelectron microscopic analysis was carried out to examine whether
      neuropeptide Y (NPY)-like immunoreactivity (-LI) is localized in mechanoreceptors
      in the lingual periodontal ligament of the rat incisor following peripheral nerve
      injury to the inferior alveolar nerve (IAN). In the lingual periodontal ligament
      of normal animals, no NPY-like immunoreactive (-IR) primary afferents were
      observed, except for a very few sympathetic perivascular nerve fibers which
      showed NPY-LI. Fourteen days following chronic constriction injury to the IAN
      combined with sympathectomy of the superior cervical ganglion, thick NPY-IR nerve
      fibers showing tree-like raminifications were detected in the shear zone between
      the tooth-related part and alveolus-related part as well as in the alveolus
      related part. Immunoelectron microscopy revealed that expanded NPY-IR nerve
      terminals were covered with several Schwann sheaths and that a part of the
      axoplasm expanded to the surrounding tissues. These ultrastructural features of
      NPY-IR structures were identical to those of periodontal Ruffini endings,
      categorized as slowly adapting mechanoreceptors. Thick (6-8 microns in diameter)
      NPY-IR axons were also observed without any apparent myelin sheath. The present
      results provide further evidence that NPY is closely associated with thick axons,
      probably myelinated nerves and Ruffini endings, following peripheral nerve
      injury.

PMID- 8876998
TI  - Inhibitory effects of cocaine on NGF-induced neuronal differentiation: incomplete
      reversibility after a critical time period.
AB  - We extend our findings showing dose-dependent cocaine inhibition of
      differentiation in NGF-stimulated PC-12 cells without affecting cell viability by
      demonstrating that neurite extension is severely limited after 24 h, maximal
      effect is reached at 36 h and recovery is only partial. Cocaine metabolites lack
      these effects. A similar process may occur following human prenatal exposure,
      perhaps through cocaine-induced changes in gene expression or other intracellular
      signalling events.

PMID- 8876997
TI  - Poly(ADP-ribose) polymerase inhibitors protect against MPTP-induced depletions of
      striatal dopamine and cortical noradrenaline in C57B1/6 mice.
AB  - Treatment of C57B1/6 mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) reduced striatal dopamine and cortical noradrenaline levels by 77-83% and
      43-46%, respectively, at 7 days post-treatment. Co-treatments with five different
      inhibitors of poly(ADP-ribose) polymerase (PARP), including benzamide,
      significantly prevented the MPTP-induced catecholamine depletions. Benzamide was
      present in the striatum, 30 min after single i.p. injection, at low millimolar
      concentrations known to selectively inhibit PARP in vitro. The protective
      activities of benzamide and its derivatives paralleled their in vitro efficacies
      and potencies both as neuroprotective agents and as inhibitors of PARP, while the
      activity of 1,5-dihydroxyisoquinoline, a structurally-unrelated compound, did
      not. In naive animals, the PARP inhibitors by themselves did not alter striatal
      dopamine levels at 7 days post-treatment. However, in acute studies, 1,5
      dihydroxyisoquinoline and nicotinamide caused marked alterations in striatal
      dopamine metabolite levels; on the contrary, benzamide and its amino-derivatives
      showed little or no effect on dopamine metabolism. These results indicate that,
      although these compounds might act at other sites in addition to PARP, PARP
      inhibitors possess neuroprotective potential in vivo and suggest a role for PARP
      in MPTP neurotoxicity.

PMID- 8876999
TI  - Heat stress reduces glutamate toxicity in cultured neurons without hsp70
      expression.
AB  - Consistent with known cytoprotective effects, mild heat stress reduced the
      vulnerability of cultured cortical neurons to glutamate-induced cell death.
      However, this neuroprotective effect occurred without expression of the inducible
      heat stress protein, hsp70, as detected by immunocytochemistry, immunoblotting,
      or metabolic labeling. Present data suggest that the anti-excitotoxic effect of
      mild heat stress is mediated outside of the traditional hsp70 mechanism.

PMID- 8877000
TI  - Enhancement of dopamine release from the striatum through metabotropic glutamate
      receptor activation in methamphetamine sensitized rats.
AB  - An intracerebral microdialysis technique was applied to study the effect of
      metabotropic glutamate receptor (mGluR) agonist on dopamine release in the
      striatum of methamphetamine (MAP)-sensitized rats. Rats were treated with MAP (1
      mg/kg, i.p.) once daily for 6 consecutive days, followed by a 6-day withdrawal.
      Perfusion of 0.1 mM (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic acid
      through a microdialysis probe placed in the striatum enhanced the extracellular
      dopamine level, and induced stereotyped behavior in MAP-sensitized rats. The
      enhancement of dopamine release and the stereotyped behavior were attenuated by
      co-perfusion of 0.4 mM RS-alpha-methyl-4-carboxyphenyl-glycine, a mGluR
      antagonist. The present results suggest that mGluRs may be involved in the
      expression of MAP-induced sensitization.

PMID- 8877001
TI  - Distribution and characterisation of the [3H](S)-zacopride labelled 5-HT3
      receptor in pig forebrain.
AB  - The present study demonstrates the presence and distribution of [3H](S)-zacopride
      labelled 5-HT3 (5-hydroxytryptamine3) receptors in pig forebrain. The
      pharmacological characterisation of 5-HT3 receptor recognition sites in
      homogenates of pig cerebral cortex provides further evidence for inter-species
      variation in the pharmacology of the 5-HT3 receptor.

PMID- 8877002
TI  - Peripherally administered GM-CSF interferes with scopolamine-induced amnesia in
      mice: involvement of interleukin-1.
AB  - We studied the effects of granulocyte-macrophage colony stimulating factor (GM
      CSF) on the classical behavioral test of scopolamine-induced amnesia for a
      passive avoidance response in the mouse. Pre-training intraperitoneal
      administration of this cytokine (1.25, 2.5, 5.0 or 10 micrograms/mouse)
      partially, although significantly, reduced the amnesic action of the muscarinic
      receptor antagonist. The peripheral administration of a specific interleukin-1
      receptor antagonist (IL-1 ra, 50 micrograms/mouse i.p.) blocked the effect of GM
      CSF. Our results suggest that GM-CSF is able to exert neuromodulatory actions and
      that it is involved (probably via IL-1) in the interactions between the immune
      system and the central nervous system.

PMID- 8877003
TI  - Prolonged subordination stress increases Calbindin-D28k immunoreactivity in the
      rat hippocampal CA1 area.
AB  - Previously we observed that corticosteroids alter Calbindin-D28k immunoreactivity
      in the rat hippocampus. In the present study we investigated whether prolonged
      subordination stress, presumably producing elevated plasma corticosterone levels
      (1) altered the immunocytochemical distribution of the Ca(2+)-binding proteins
      Calbindin-D28k (CBir) and Parvalbumin (PVir) in the rat hippocampus, and (2)
      induced ongoing neurodegenerative changes using a silver impregnation method.
      Eight days of subordination stress reduced body weight, increased adrenal weight
      corrected for body weight and reduced thymus weight, indicating its effectiveness
      to produce a stressful situation. Stress increased CBir selectively in the CA1
      pyramidal cell layer whereas PVir was not altered. Silver-impregnation revealed
      no ongoing neurodegenerative changes in any of the hippocampal subfields.

PMID- 8877004
TI  - Extracellular dopamine in the rat ventral tegmental area and nucleus accumbens
      following ventral tegmental infusion of cocaine.
AB  - Rats were implanted with dual dialysis probes, one in the ventral tegmental area,
      and another one ipsilateral in the nucleus accumbens. Infusion of cocaine (10,
      100, 1000 mM) into the ventral tegmental area gradually increased extracellular
      dopamine to 164, 329 and 991% of baseline in the ventral tegmental area, but
      reduced dopamine to 76, 47 and 38% of baseline in the nucleus acumbens. These
      results are consistent with cocaine-induced feedback regulation of dopamine cell
      activity involving somatodendritic impulse regulating dopamine D2 autoreceptors.

PMID- 8877005
TI  - Long-term culture of primary breast cancer in defined medium.
AB  - Over a period of 6 1/2 years between January 1986 and May 1992, 135 unselected
      primary breast cancers were cultured and of these 10 developed into cell lines.
      Six of the lines grew in defined serum-free medium, while the other four required
      supplementation with 0.5% fetal calf serum. Two of the lines are from the same
      breast, being derived from a local excision specimen and from a mastectomy
      specimen 12 months later. In addition, 12 lymph nodes containing metastatic
      breast cancer were cultured; one of these cultures became permanent in a defined
      serum-free medium. Oestrogen receptor (ER) status was negative in all but one of
      the tumours which grew successfully, and even in this case the derived cell line
      is ER negative. The epithelial nature of the lines has been confirmed by
      immunocytochemistry and by electron microscopy (EM), while their malignant nature
      is shown by morphology, unattached growth, chromosome analysis, and, in the case
      of the line from a lymph node metastasis, the absence of any benign source of
      epithelial cells.

PMID- 8877006
TI  - An evaluation of the quality of life among long-term survivors of breast cancer.
AB  - Attention to the quality of life (QOL) among long-term of breast cancer is long
      overdue. Modest improvements in overall survival have led to a greater emphasis
      on how women are living with the disease. The purpose of this paper is to report
      the results of a descriptive study that evaluated the quality of life of 294
      breast cancer survivors, and to review the continuum of positive and negative QOL
      outcomes in this population. Members of the National Coalition for Cancer
      Survivorship (NCCS) were surveyed and received two QOL instruments: the Quality
      of Life-Cancer Survivors Tool (QOL-CS) and the Functional Assessment of Cancer
      Therapy (FACT-G), and a demographic data tool. The main research variables were
      the subscales (Physical, Psychological, Social, and Spiritual Well-being) and
      individual items of the QOL-CS and the FACT-G. Results indicated that: a)
      fatigue, aches and pains, and sleep problems were persistent after treatment
      ended; b) psychological distress from cancer diagnosis and treatment, and fear of
      recurrent, metastatic, and recurrent disease were problematic over time; c)
      family distress, sexuality, and family burden issues were of greatest social
      concern; and d) uncertainty over the future plagued breast cancer survivors long
      term. Breast cancer survivors also reported good outcomes in hopefulness, having
      a life purpose, and having a positive change after the treatment. CONCLUSIONS:
      breast cancer survivors experienced long-term changes after completion of
      treatment which affected overall quality of life. However, many positive benefits
      were also gained which helped to balance the worse outcomes.

PMID- 8877007
TI  - Circulating levels of the macrophage colony stimulating factor CSF-1 in primary
      and metastatic breast cancer patients. A pilot study.
AB  - Earlier results [1], suggesting an autocrine tumor cell stimulation by CSF-1, are
      in agreement with data by Fildermann et al. [2], showing an enhanced motility and
      invasiveness in the CSF-1 receptor expressing BT20 breast cancer cell line upon
      stimulation with recombinant CSF-1. Tumor-cell secreted CSF-1 has also been shown
      to cause monocyte recruitment, but not cytotoxicity [3]. Down-regulation of
      monocyte class II antigen expression after exposure to high concentrations of CSF
      1 [4] may decrease macrophage-mediated tumor cytotoxicity and favor tolerance.
      Raised CSF-1 serum levels may thus increase tumor metastatic behavior as well as
      cause immune suppression in advanced stage disease. We set out to evaluate serum
      CSF-1 levels in primary and metastatic breast cancer. Serum samples from one
      hundred and eighteen primary breast cancer patients and seventy-five patients
      with metastatic disease were assayed by radio-immuno-assay (RIA) for circulating
      colony-stimulating factor 1. Mean serum levels were significantly higher in the
      metastatic population (9.7 ng/ml +/- 0.8) as compared to the patients with
      primary tumors (4.2 +/- 0.2) (p = 0.0001). Patients with early stage tumors
      (T0/T1/T2) had significantly lower levels than patients with tumors of larger
      size (T3/T4) (p = 0.0001). Relapse and survival statistics were analyzed using
      Kaplan-Meier estimates. Samples from 118 primary breast cancer patients were
      available to study. The median follow up was 85 months (range: 1-108). An
      elevated CSF-1 concentration (> 6.6 ng/ml or > 550 Units/ml) was associated with
      a shorter disease free interval (p = 0.03). In a multivariate analysis, including
      T (clinical tumor size), N (clinical node status), histological grade, and
      hormone receptor status, CSF-1 remained significantly associated with a poorer
      outcome (relative risk of relapse: RR: 3.3 [1.3-8.5]), together with tumor size
      (RR: 2.8[1-8.2]) and clinically involved nodes (RR: 4.1[2.1-8]). These results
      were not modified following adjustment for type of treatment. We conclude that
      raised circulating CSF-1 levels may be an indicator of early metastatic relapse.

PMID- 8877008
TI  - Vinorelbine: an active, non cross-resistant drug in advanced breast cancer.
      Results from a phase II study.
AB  - PURPOSE: To evaluate efficacy and toxicity of vinorelbine and to investigate its
      cross-resistance with other current drug treatments for metastatic breast cancer.
      PATIENTS AND METHODS: From July 1992 to December 1993, 57 histologically proven
      breast cancer patients entered this Phase II study. Patients were stratified
      according to their status of previous treatment, namely, no prior chemotherapy or
      relapse more than 12 months since the end of adjuvant chemotherapy (Group A) and
      other patients (Group B). RESULTS: Fifty three patients were evaluable for
      response, 27 in Group A and 26 in Group B. All patients were evaluable for
      toxicity. Vinorelbine was initially administered at the dose of 30 mg/sqm weekly
      by i.v. infusion in 100 ml of normal saline over 20 minutes. A frequency analysis
      of drug administration in the first 20 cases revealed two main treatment
      periodicities, corresponding to one week and to three weeks. Thereafter the drug
      was administered at 30 mg/sqm on day 1 and 8, every 3 weeks. With the new drug
      schedule, the mean dose intensity increased from 19.7 to 21.1 mg/sqm per week.
      Overall, an objective response rate of 47% (95% C.I. 33%-61%) was documented.
      Four patients achieved complete response (7%, CI: 2%-18%) and 21 partial response
      (40%, CI: 26%-54%). Fifty nine percent of patients in Group A and 35% in Group B
      showed objective tumor response. The analysis of response rate in previously
      treated patients failed to show evidence of cross-resistance with vinorelbine.
      Main side effects, i.e. neutropenia, local pain, and gastrointestinal and flu
      like symptoms, were moderate and short lasting. CONCLUSION: Vinorelbine has
      clinically significant activity in metastatic breast cancer, and no cross
      resistance with prior anthracyclines and CMF treatments. The drug schedule of 30
      mg/sqm iv bolus on day 1 and 8 every 3 weeks was found effective and tolerable.

PMID- 8877010
TI  - Phase II study of intensive chemotherapy with autologous bone marrow
      transplantation in patients in complete remission of disseminated breast cancer.
AB  - BACKGROUND: This trial studied the disease-free survival after high-dose
      chemotherapy in patients in complete remission of metastatic breast cancer.
      PATIENTS AND METHODS: Thirty women, mean age 42.2 years (range 33-55) with
      metastatic breast cancer, received high-dose chemotherapy in a phase II study.
      Patients were eligible if they were < or = 55 years of age, had achieved complete
      remission within 6 months of the initiation of chemotherapy, and had a WHO
      performance scale of 0 or 1. The high-dose regimen consisted of melphalan 180
      mg/m2 and mitoxantrone 60 mg/m2 both divided over 3 days. On day 7 bone marrow
      and/or peripheral stem cells were infused. After bone marrow recovery, external
      beam radiation was administered to sites of previous metastatic disease in 15
      patients. RESULTS: Apart from leuko- and thrombocytopenia, mucositis was the
      major side effect. One patient died during the bone marrow transplant period due
      to an aspergillus infection. The median follow-up since high-dose chemotherapy is
      25 months (range 13 to 56 months). The median disease-free survival since high
      dose chemotherapy is 27 months and the disease free survival is still 43% with an
      overall survival of 53% at 3 years. In two patients tumor relapse occurred only
      in the brain; in one patient the only relapse sign was a meningeal carcinosis. At
      the moment 17 patients are disease-free (13(+)-56+) months after high-dose
      chemotherapy. CONCLUSION: Until now this high-dose regimen in selected patients
      with complete remission after induction chemotherapy for metastatic breast cancer
      has a promising disease free survival.

PMID- 8877009
TI  - Structure-activity relations of S-adenosylmethionine decarboxylase inhibitors on
      the growth of MCF-7 breast cancer cells.
AB  - SAMDC is a key enzyme in the biosynthesis of spermidine and spermine, 2
      polyamines that are essential for cell proliferation. Inhibition of polyamine
      biosynthesis is often targeted as a therapeutic strategy to suppress cancer cell
      growth as these cells contain elevated levels of polyamines. We examined the
      effect of a new group of SAMDC inhibitors, CGP33829, CGP35753, CGP36958,
      CGP39937, and CGP48664, (obtained from Ciba-Geigy, Basel, Switzerland), and their
      parent compound, MGBG, on the proliferation of MCF-7 breast cancer cells. MGBG
      had minimal effects on the proliferation of MCF-7 cells up to 6 microM
      concentration. In contrast, CGP48664 and CGP39937, containing 2 aromatic rings
      that delocalize the pi electron system of the backbone of MGBG, were potent
      inhibitors with 50% growth inhibition at 0.5 microM concentration. Other CGP
      compounds were less effective in inhibiting cell growth. The ability of CGP48664
      to inhibit MCF-7 cell proliferation was related to its ability to inhibit SAMDC
      and to consequently deplete spermidine and spermine levels in the cell. Exogenous
      spermidine and spermine could reverse the growth inhibitory effects of this
      compound. CGP compounds also increased the activity of ODC, another enzyme
      involved in polyamine biosynthesis. Northern blot analysis of mRNA from MCF-7
      cells progressing in cell cycle after G1 synchronization did not show an increase
      in ODC mRNA level by CGP48664. These data demonstrate structure-activity
      relationships of a series of MGBG derivatives on cell growth, enzyme activities,
      and polyamine biosynthesis in a hormone-responsive breast cancer cell line and
      suggest potential application of SAMDC inhibitors as therapeutic agents.

PMID- 8877011
TI  - Birth season and breast cancer risk in Japan.
AB  - Recent studies suggest that prenatal or early post-natal factors may influence
      future breast cancer risk. To investigate whether month of birth is a risk factor
      for breast cancer, we analyzed the distribution of month of birth for 81,162
      women died of breast cancer and 1,334,650 women died of cancers at all sites, who
      were reported to the Ministry of Health and Welfare from 1972-90 in Japan. After
      considering each birth year seasonal variations in month of birth were not shown
      statistically significant in any age-group through using chi 2 test (df = 11).
      The negative results were also confirmed in residential area and period category.

PMID- 8877012
TI  - Femoral fractures in postmenopausal breast cancer patients treated with adjuvant
      tamoxifen.
AB  - The anti-estrogen tamoxifen is the prevalent endocrine treatment in
      postmenopausal breast cancer patients. However, nothing is known about the long
      term effects of the drug on the skeleton as assessed by the occurrence of
      fractures. We investigated the occurrence of fractures of the femur in patients
      from a Danish Breast Cancer Cooperative Group (DBCG) trial initiated in 1977 by a
      linkage of data from the Danish National Registry of Patients with data from the
      DBCG registry. 1716 postmenopausal women with high-risk breast cancer were
      randomized to local radiotherapy with or without tamoxifen, 30 mg daily for 1
      year. Fifty-one patients in the control group had one femoral fracture and 64
      tamoxifen treated patients had one femoral fracture. Eleven patients in the
      control group had one trochanteric fracture compared to 27 patients in the
      tamoxifen group (logrank = 5.28. P = 0.022; hazard ratio = 2.12, 95% CL 1.12,
      4.01). The results could not be explained by a longer survival in the tamoxifen
      group nor by bone metastases with pathological fractures. In conclusion, our
      study suggests that tamoxifen does not seem to offer protection against fractures
      in old age and may even increase the risk of fractures at particular sites. This
      hypothesis needs to be disproved or confirmed in other trials.

PMID- 8877013
TI  - Protein tyrosine kinase activity in 350 T1/T2, N0/N1 breast cancer. Preliminary
      results.
AB  - Protein tyrosine kinases (PTKs) are a family of enzymes sharing a highly
      conserved catalytic domain which phosphorylates substrate proteins on tyrosine
      residues. PTKs play a major role in the transduction of the mitogenic signal and
      are involved in the control of cell proliferation, differentiation, and
      transformation processes. PTKs can be subdivided into two major types: membrane
      associated PTKs consisting essentially of growth factor receptors (receptor
      tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular
      transduction of mitogenic and differentiation signals. From January 1988 to
      January 1992, PTK activity was assayed in cytosolic fractions prepared from 350
      T1-T2, N0-N1 M0, breast carcinomas. Enzymatic activity was measured using
      phosphate transfer from [32P]-ATP to poly-Glu-Tyr as an artificial substrate.
      According to our previously reported pilot study, we chose a cut-off value of 12
      pmol 32P incorporated min-1 mg-1 protein, corresponding to the median value. We
      found positive PTK levels (> or = 12 pmol/min/mg) to be correlated with a loss of
      differentiation according to Scarff-Bloom grade (p < 0.001), negative PR (p =
      0.03) and ER status (p = 0.04). With a median follow-up of 30 months (0-82),
      patients with a positive PTK level presented a smaller 3-year disease free
      survival than in the PTK negative group of patients (p = 0.07). In Cox
      multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK
      activity does not emerge as a significant prognostic factor.

PMID- 8877014
TI  - Influence of plasma estrogen levels on the length of the disease-free interval in
      postmenopausal women with breast cancer.
AB  - The influence of plasma estrogen levels on disease-free interval (time from
      primary treatment to first relapse, DFI) in breast cancer patients is not known.
      Any relation between plasma estrogens and the outcome in breast cancer patients
      may have implications considering use of hormone replacement therapy (HRT) in
      patients treated for breast cancer. We measured plasma estradiol (E2), estrone
      (E1), and estrone sulfate (E1S) in 92 postmenopausal women with breast cancer
      relapse and correlated plasma estrogen levels to the length of their disease-free
      interval (DFI1) and the length of the DFI in the subgroup of patients in whom
      this extended a time period of more than 2 years (DFI2). The length of DFI2
      correlated negatively to plasma level of E1S (p < 0.025) and E2 (p < 0.05) and to
      the E2/E1 and E1S/E1 ratios (p < 0.05), while the length of DFI1 correlated
      negatively to plasma level of E1S (p < 0.025) and the E1S/E1 ratio (p < 0.005).
      We also analyzed for possible correlations between DFIs and plasma estrogen
      levels in subgroups based on tumor stage at diagnosis and previous therapy. In
      general, these subgroup analyses revealed negative correlations of statistical
      significance or borderline significance between the DFI1 and DFI2 and E2 and the
      E2/E1 ratio and non-significant negative correlations between plasma levels of
      E1S and DFI1 and DFI2. In particular, strong negative correlations between plasma
      estrogen levels and the length of DFI1 and DFI2 were found among patients
      responding to first line endocrine treatment for relapse and among patients with
      primar stage III tumors. Our findings suggest plasma E2 and E1S to stimulate the
      growth of micrometastases in patients treated for breast cancer.

PMID- 8877015
TI  - Cytogenetic studies on a patient with prepubertal breast cancer: a case report.
AB  - Cytogenetic studies were carried in a 10 year old girl with prepubertal breast
      cancer for assessing inherited genetic susceptibility to chromosome breakage. The
      girl presented with a tumour in the left breast. Histologically it was diagnosed
      as secretory carcinoma (SC). Chromosome anomalies observed in phytohemagglutinin
      (PHA-P) stimulated lymphocytes were del(2)(q33), del(3)(p24), del(7)(q22) and
      dup(12)(p11p12). The regions involved have been reported in breast tumors. These
      loci, detected in peripheral blood lymphocytes (PBL), could be the sites
      susceptible to breakage, its subsequent effect being manifested in the target
      (breast) tissue.

PMID- 8877016
TI  - Comment on 'when can stereotactic core biopsy replace excisional biopsy'?

PMID- 8877017
TI  - Estimating impossible curves using NONMEM.
AB  - 1. On fitting model equations to experimental data, the situation may arise that
      individual subjects provide insufficient information to obtain adequate parameter
      estimates due to the fact that not all aspects are exhibited by all subjects or
      that the models are simply too complex. This may be solved by applying nonlinear
      mixed effect modelling to the data, which integrates the information provided by
      different subjects. 2. We aim to provide insight into the methodology and its use
      in these situations, illustrated by three examples: determination of
      pharmacokinetics in a rising dose design, where the lower doses provide
      insufficient information (due to assay limitations) to estimate terminal half
      life; determination of the kinetics of the low molecular weight heparin
      enoxaparine (Clexane) using anti-Xa activity, effectively dealing with lingering
      low/basal activity; simultaneous estimation of the pharmacokinetics and
      pharmacodynamics of the low molecular weight heparin dalteparin (Fragmin) after
      subcutaneous and intravenous administration.

PMID- 8877018
TI  - Clinical pharmacology of beta 3-adrenoceptors.
AB  - 1. An atypical non beta 1/beta 2-adrenoceptor (AR) subtype (beta 3-AR) has been
      identified which is selectively stimulated by a group of ligands which mediate
      lipolytic and thermic responses in brown and white adipose tissue. 2. Molecular
      studies have shown that beta 3-AR in man are mainly expressed in visceral
      adipocytes, and to a lesser extent in gall-bladder and colon. In vitro studies
      with beta 3-AR agonists have shown activity at other sites including skeletal
      muscle and myocardium. 3. Regulation of beta 3-AR may differ from beta 1/beta 2
      AR subtypes in that continuous agonist exposure does not result in receptor down
      regulation. 4. A polymorphism of the human beta 3-AR gene (Trp64Arg) has been
      identified which is associated with obesity, insulin resistance and an earlier
      onset of non-insulin-dependent diabetes mellitus (NIDDM). Studies are required to
      establish whether expression of the mutant gene results in altered metabolic
      responses to beta 3-AR stimulation in man. 5. There is accumulating evidence to
      support a therapeutic role of beta 3-AR agonists in NIDDM because of anti-obesity
      and anti-diabetic activity, as a consequence of thermogenic effects as well as
      increased insulin sensitivity and glucose tolerance. 6. Selectivity studies with
      BRL35135 and isoprenaline in humans have demonstrated a beta 3-AR mediated
      component to thermogenesis which is dissociated from beta 1/beta 2-mediated
      effects on carbohydrate and fat metabolism. Similar studies have suggested a
      functional beta 3-AR mediating cardiac but not airway responses in humans. An
      evaluation of beta 3-AR agonists in irritable bowel syndrome may be warranted in
      view of colonic antimotility properties in vitro.

PMID- 8877019
TI  - The effect of age on the pharmacokinetics of the opioid antagonist nalmefene.
AB  - 1. The disposition of nalmefene was evaluated in young and elderly normal healthy
      volunteers. Subjects received either a single 1 mg (n = 18 young; n = 11 elderly)
      or 2 mg (n = 8 young; n = 15 elderly) intravenous bolus dose of nalmefene. 2.
      Following the administration of nalmefene, the initial plasma concentrations were
      significantly higher in elderly vs young subjects. The higher concentrations were
      the result of the 30 to 40% smaller central compartment apparent volume of
      distribution that was observed in the elderly subjects as compared with the young
      volunteers (2.8 +/- 1.1 vs 3.9 +/- 1.11 kg-1 for 1 mg dose). The elderly
      volunteers also had a significantly shorter distributional half-life (t1/2 lambda
      1) than young volunteers (0.7 +/- 0.7 vs 1.3 +/- 0.8 h for 1 mg dose). No
      significant differences between groups were observed for the elimination half
      life, clearance or steady-state apparent volume of distribution. 3. Although
      transiently higher nalmefene plasma concentrations were observed in the elderly
      immediately following drug administration, there was no association between this
      observation and adverse events. We conclude that no dosage alteration is
      warranted in elderly patients.

PMID- 8877020
TI  - A randomized, double-blind, placebo-controlled trial comparing pethidine to
      metamizol for treatment of post-anaesthetic shivering.
AB  - 1. Shivering is frequent during the post-anaesthetic recovery period, and there
      is no clear consensus about the best strategy for its treatment. We tested the
      efficacy of two commonly used analgesic drugs, pethidine and metamizol. 2. A
      randomized, double-blind, placebo-controlled clinical trial was performed,
      including 104 adult patients who presented with post-anaesthetic shivering during
      the recovery from general anaesthesia. They were randomized to receive placebo (n
      = 32), metamizol 25 mg kg-1 (n = 37), or pethidine 0.4 mg kg-1 (n = 35). The
      response to treatment was assessed 5, 15 and 45 min after drug administration,
      and the main outcome variable was complete suppression of shivering. 3. The
      efficacy at 5, 15 and 45 min was as follows: placebo 6%, 16% and 37%; metamizol
      13.5%, 32% and 76%, and pethidine 89%, 91% and 89%. With both active drugs the
      efficacy at all three time intervals was significantly higher than that with
      placebo (P < 0.05). The differences (at 5 and 15, but not at 45 min) between
      pethidine and metamizol were statistically significant (P < 0.05). Both drugs
      were well tolerated. 4. The persistence of shivering at 45 min in two thirds of
      placebo-treated patients indicates that drug treatment is worthwhile; metamizol
      produces a better postanaesthetic shivering response than placebo, especially 15
      and 45 min after drug administration; the efficacy of pethidine was the highest
      and the response to it appeared more quickly; however, at 45 min it was similar
      to that observed with metamizol. 5. Both metamizol and pethidine suppress
      postanaesthetic shivering, but the latter induces a quicker and more reliable
      response.

PMID- 8877021
TI  - Taste loss to terbinafine: a case-control study of potential risk factors.
AB  - 1. To identify risk factors associated with taste loss to terbinafine, we
      performed a case-control study of 87 reports of probably terbinafine-induced
      taste loss and 362 controls on terbinafine without taste loss, who had filled
      prescriptions from the same pharmacy and GP. Data on general health, diet,
      alcohol, smoking, drug use and medical history were collected by means of a self
      administered questionnaire. 2. The mean latent period between first intake of
      terbinafine and taste loss was 35 days. Most patients recovered within 4 months
      after discontinuation. Cases were significantly older than controls. The odds
      ratio of taste loss in patients of 65 years and older was 4.4 in comparison with
      persons younger than 35 years of age (95% CI: 1.4-16.1). The risk in persons with
      a body mass index (BMI) below 21 kg m-2 was 4.4 times higher than in those with a
      BMI of more than 27 kg m-2 (95% CI: 1.6-14.2). The risk of taste loss in patients
      of 55 years and older with a BMI below 21 kg m-2 was 12.8 times higher than that
      in patients below 35 years of age (95% CI: 1.9-88.6). 3. A low BMI, a history of
      taste loss, and ageing are risk factors for developing taste loss to terbinafine.
      Prescription of this drug to elderly patients with low BMI and low daily intake
      of nutrients requires careful follow-up.

PMID- 8877022
TI  - A prospective study of adverse drug reactions as a cause of admission to a
      paediatric hospital.
AB  - 1. A total of 512 consecutive paediatric hospital admissions of children 2 years
      old or less were evaluated to assess the extent and pattern of admission caused
      by suspected adverse drug reactions (ADRs). the proportion of suspected ADRs
      related to hospital admissions was 4.3%. 2. The organ-systems most commonly
      implicated were the central nervous system (40.5%), digestive system (16.7%), and
      skin and appendages (14.3%). Together, they accounted for 71.5% of admissions
      attributed to ADRs. The most common clinical manifestations inducing admission
      were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever,
      itching and apnoea (2 cases each). 3. The four classes of drugs most frequently
      suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective
      agents (25%), drugs active on the central nervous system (15%) and drugs used in
      dermatology (10%). The most common drugs related to ADRs were a combination of
      chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid
      (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and
      antipolio vaccine (2 cases each). 4. There were no significant differences
      between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37
      2.17) or between the sexes as regards hospital admittance due to suspected ADRs
      (odds ratio 1.94; 95% CI 0.72-5.42). 5. The results of this kind of study may be
      influenced by patterns of drug utilization. Nevertheless, the lack of specific
      studies of drug effects in young children makes it desirable to carry out
      pharmacoepidemiological studies in this age group.

PMID- 8877023
TI  - Single-dose pharmacokinetics of ampicillin and tobramycin administered by
      hypodermoclysis in young and older healthy volunteers.
AB  - 1. To test the feasibility of administering antibiotics by subcutaneous infusion
      to the elderly, we compared the pharmacokinetics of tobramycin (single dose of 80
      mg) given by hypodermoclysis (HDC) with the kinetics of the antibiotic injected
      intravenously (i.v.) in 10 young (< 50 years old) and 10 elderly (> 65 years old)
      healthy volunteers. Similar studies were performed with ampicillin (single dose
      of 1 g) in 12 young and 10 older healthy volunteers. 2. Compared with the i.v.
      route, HDC delayed the time to reach the maximal plasma concentration (tmax) of
      tobramycin in young volunteers: 32 +/- 6 (s.d.) min vs 88 +/- 46, P < 0.005, and
      older volunteers: 27 +/- 4 min vs 89 +/- 15, P < 0.005. Administration of the
      antibiotics by HDC was well tolerated. The plasma concentration of tobramycin 30
      min after the end of infusion (C60) was lower (P < 0.05) following HDC than after
      the i.v. route in both young, 2.2 +/- 0.7 vs 3.5 +/- 0.8 micrograms ml-1, and
      elderly subjects, 2.2 +/- 0.8 vs 3.8 +/- 0.9. micrograms ml-1. 3. The area under
      the curve (AUC) of tobramycin given by HDC was slightly smaller than when given
      i.v., i.e. in young subjects: 740 +/- 225 (s.d.) vs 893 +/- 223 micrograms ml-1
      min, NS, and in the elderly: 980 +/- 228 vs 1056 +/- 315 micrograms ml-1 min, NS.
      4. When ampicillin was administered by HDC, the tmax was also delayed in young
      volunteers: 45 +/- 18 vs 23 +/- 6 min, and in the elderly: 49 +/- 18 vs 27 +/- 4
      min, P < 0.005, the AUC was greater by HDC than i.v. in the young volunteers:
      4527 +/- 1658 micrograms ml-1 min vs 3810 +/- 1033 micrograms ml-1 min and in the
      elderly: 6795 +/- 2094 micrograms ml-1 min vs 4217 +/- 1518 micrograms ml-1 min,
      and the C60 was higher by HDC in the young: 27 +/- 7 vs 24 +/- 9 micrograms ml-1,
      and in the elderly: 32 +/- 9 vs 23 +/- 11 micrograms ml-1, P < 0.05. 5. In
      conclusion, HDC delays the entry of the antibiotic into the systemic circulation,
      but did not affect the amount available. HDC was well tolerated and could become
      an adequate method for antibiotic administration to the elderly.

PMID- 8877024
TI  - Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase
      inhibitors on serum ubiquinone and blood lactate/pyruvate ratio.
AB  - 1. Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a
      central compound of the mitochondrial respiratory chain. The main adverse effect
      of statins is a toxic myopathy possibly related to mitochondrial dysfunction. 2.
      This study was designed to evaluate the effect of lipid-lowering drugs on
      ubiquinone (coenzyme Q10) serum level and on mitochondrial function assessed by
      blood lactate/pyruvate ratio. 3. Eighty hypercholesterolaemic patients (40
      treated by statins, 20 treated by fibrates, and 20 untreated patients, all 80
      having total cholesterol levels > 6.0 mmol l-1) and 20 healthy controls were
      included. Ubiquinone serum level and blood lactate/pyruvate ratio used as a test
      for mitochondrial dysfunction were evaluated in all subjects. 4. Lactate/pyruvate
      ratios were significantly higher in patients treated by statins than in untreated
      hypercholesterolaemic patients or in healthy controls (P < 0.05 and P < 0.001).
      The difference was not significant between fibratetreated patients and untreated
      patients. 5. Ubiquinone serum levels were lower in statin-treated patients (0.75
      mg l-1 +/- 0.04) than in untreated hypercholesterolaemic patients (0.95 mg l-1 +/
      0.09; P < 0.05). 6. We conclude that statin therapy can be associated with high
      blood lactate/ pyruvate ratio suggestive of mitochondrial dysfunction. It is
      uncertain to what extent low serum levels of ubiquinone could explain the
      mitochondrial dysfunction.

PMID- 8877025
TI  - Racial differences in propranolol enantiomer kinetics following simultaneous i.v.
      and oral administration.
AB  - 1. Racial differences in propranolol enantiomer kinetics following oral dosing
      were previously documented in our laboratory. The purpose of this study was to
      more completely describe propranolol kinetics in black and white subjects with
      the goal of gaining a better understanding of the mechanism(s) responsible for
      racial differences in oral propranolol kinetics. 2. Twelve white and 13 black
      healthy males were included in the study. Poor metabolizers of dextromethorphan
      and mephenytoin were excluded. Subjects took oral propranolol 80 mg every 8 h for
      16 doses and received an intravenous dose of radiolabelled propranolol with the
      16th dose. Serum and urine samples were collected for 24 h after the 16th dose.
      Serum concentrations of R- and S-propranolol and urine concentrations of its
      three primary metabolites were determined by h.p.l.c. 3. Apparent oral clearances
      of R- and S-propranolol were higher (P < 0.05) in blacks than whites (R
      propranolol: 5036 +/- 4175 ml min-1 vs 2854 +/- 879 ml min-1; S-propranolol 3255
      +/- 1723 ml min-1 vs 2125 +/- 510 ml min-1; blacks vs whites). 4. R- and S
      propranolol clearances were higher in blacks than whites (R-propranolol 1069 +/-
      316 ml min-1 vs 841 +/- 161 ml min-1; S-propranolol 947 +/- 271 ml min-1 vs 771
      +/- 142 ml min-1; blacks vs whites, P < 0.05). 5. There were trends (P > 0.05 <
      0.10) toward higher side chain oxidation, 4-hydroxylation and R-propranolol
      glucuronidation in blacks compared with whites. Ethnic differences in the
      enantiomeric ratios of partial metabolic clearance values were not observed. 6.
      We conclude the higher propranolol oral clearances in black subjects are
      explained by blacks having slightly higher hepatic metabolism via all three of
      its major metabolic pathways. Higher propranolol clearances among black subjects
      were also observed and we conclude this finding is explained largely by the
      higher hepatic metabolism, but also by slightly higher liver blood flow among
      black subjects.

PMID- 8877026
TI  - The effect of fluconazole and ketoconazole on the metabolism of
      sulphamethoxazole.
AB  - 1. Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine
      has been implicated in the hypersensitivity reactions associated with co
      trimoxazole administration. Inhibiting the formation of the hydroxylamine may be
      one method of preventing the high frequency of toxicity which is observed in HIV
      infected patients. Therefore, in this study, we have investigated the ability of
      fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the
      formation of sulphamethoxazole hydroxylamine. 2. Ten healthy male volunteers were
      given co-trimoxazole (800 mg sulphamethoxazole and 160 mg trimethoprim) alone or
      1 h after either fluconazole (150 mg) or ketoconazole (200 mg) in a randomized
      fashion with a washout period of at least 1 week between each phase. Urine was
      collected for 24 h, and sulphamethoxazole and its metabolites were quantified by
      electrospray LC-MS. 3. Ketoconazole had no effect on the urinary recovery of
      sulphamethoxazole or any of its metabolites. In contrast, fluconazole
      significantly (P < 0.001) inhibited the formation of sulphamethoxazole
      hydroxylamine by 50.0 +/- 15.1%. Fluconazole also inhibited the oxidation of
      sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites
      by 69.9 +/- 15.8% and 64.0 +/- 12.0%, respectively, but had no effect on the
      amount of sulphamethoxazole, N4-acetyl sulphamethoxazole, or sulphamethoxazole N1
      glucuronide excreted in urine. 4. The potential clinical benefit of using
      fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS
      needs to be assessed in a prospective study using both metabolite formation and
      the clinical occurrence of adverse reactions as end-points.

PMID- 8877027
TI  - Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in
      athletes. Blood sampling and doping control.
AB  - 1. The pharmacokinetics of recombinant human erythropoietin (rHuEpo) were
      initially determined in two healthy volunteers after a single subcutaneous dose
      (50 u kg-1). Twenty subjects then received repeated subcutaneous administrations
      of high dose (200 u kg-1) rHuEpo and 10 subjects received placebo. An
      immunoradiometric assay was used to measure the concentrations of erythropoietin
      (Epo) in serum and urine. 2. Serum Epo concentration-time profiles were best
      described by a one-compartment open model with zero-order input. The mean
      elimination half-life (+/- s.d.) was 42.0 +/- 34.2 h. Clearance, uncorrected for
      bioavailability, was 0.05 +/- 0.011 h-1 kg-1. Erythropoietin concentrations
      returned to normal values in serum and urine, 7 and 4 days after the last
      administration, respectively. 3. The recombinant hormone was well tolerated.
      Significant changes in reticulocytes and red blood cells, haemoglobin
      concentrations and haematocrit were observed after administration of rHuEpo. In
      the control group, these parameters remained unchanged. 4. The change in
      reticulocytes was used as an index of the therapeutic effect of rHuEpo. The
      concentration-effect relationship was best described by an exponential model. 5.
      These data show the limitations of the measurement of Epo concentrations in blood
      and urine samples, collected in athletes during competition, for antidoping
      control. Epo doping can be detected only during or within 4 to 7 days of ending a
      course of rHuEpo.

PMID- 8877028
TI  - gamma-L-glutamyl-5-hydroxy-L-tryptophan, but not gamma-L-glutamyl-L-tryptophan,
      causes sodium retention in normal man.
AB  - 1. This randomized, placebo-controlled, cross-over study compared the relative
      effectiveness of gamma-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP) and gamma-L
      glutamyl-L-tryptophan (glu-TRP) in terms of their ability to act as substrates
      for renal 5-hydroxytryptamine (5-HT) synthesis and their actions on urinary
      sodium excretion. 2. Urinary excretion of 5-HT and sodium were determined before,
      during and after 1 h intravenous infusion of an equimolar amount (45 nmol kg-1
      min-1) of glu-5-HTP or glu-TRP or placebo in nine healthy male subjects. 3.
      Cumulative urinary 5-HT excretion over the 4 h after the start of glu-5-HTP
      infusion was 350-fold greater than that after placebo, and this was associated
      with a reduction in the urinary excretion of sodium. 4. In contrast, the urinary
      excretion values of 5-HT and sodium after administration of glu-TRP were not
      significantly different from those observed on the placebo day. 5. The marked
      increase in urinary 5-HT excretion and the retention of sodium after
      administration of glu-5-HTP have been demonstrated in previous studies and result
      from increased intrarenal generation of 5-HT. The absence of a rise in urinary
      excretion of 5-HT after glu-TRP infusion suggests that there was no significant
      conversion of this glutamyl compound to 5-HT within the kidney. As a result,
      there was no effect on urinary sodium excretion.

PMID- 8877029
TI  - Suppression of vagus-mediated pancreatic polypeptide release by the mu-opiate
      receptor agonist loperamide in man.
AB  - 1. Morphine suppresses the release of pancreatic polypeptide, a hormone under
      vagal cholinergic control. The intention of the study was to detect whether the
      mu-opiate receptor agonist loperamide is also able to inhibit pancreatic
      polypeptide release, and to define its site of action. 2. In groups of healthy
      subjects (n = 6 each) stimulation of pancreatic polypeptide was assessed in five
      different tests: (i) insulin-hypoglycaemia; (ii) modified sham feeding; (iii)
      intravenous infusion of the cholecystokinin analogue ceruletide; (iv) injection
      of corticotropin releasing hormone; (v) infusion of the muscarinic acetylcholine
      agonist bethanechol. All tests were performed after oral application of either a
      placebo or loperamide (16 mg), tests (ii) and (iii) were repeated with loperamide
      in smaller doses (2 and 6 mg), with loperamide plus naloxone, with naloxone
      alone, and with infusion of atropine. Plasma concentrations of pancreatic
      polypeptide were measured radioimmunologically. 3. Release of pancreatic
      polypeptide in test (i) to (iv) was completely blocked by 16 mg loperamide,
      whereas bethanechol-stimulated release (test 5) was not influenced. Tests (ii)
      and (iii) showed that the inhibition was dose-dependent and could be attenuated
      by naloxone. The inhibitory effect of loperamide was comparable with that of
      atropine. 4. We conclude that loperamide causes a dose-dependent inhibition of
      pancreatic polypeptide release mediated by vagal-cholinergic pathways, but does
      not have an atropine-like peripheral action.

PMID- 8877030
TI  - Pharmacokinetics, pharmacodynamics, long-term efficacy and safety of oral 1
      deamino-8-D-arginine vasopressin in adult patients with central diabetes
      insipidus.
AB  - 1. The pharmacokinetics and pharmacodynamics of intranasal (IN) and oral 1
      deamino-8-D-arginine vasopressin (DDAVP) were compared in 10 Chinese adults with
      central diabetes insipidus previously controlled on IN DDAVP. This was followed
      by comparison of the acute pharmacodynamics of commonly used oral preparations
      (containing 100, 200 and 400 micrograms per tablet) and a 1 year prospective
      evaluation of the long-term safety and efficacy of oral DDAVP. 2. Following 20
      micrograms IN and 200 micrograms orally, respective plasma DDAVP concentrations
      peaked after 45.6 +/- 7.3 and 93.3 +/- 3.3 (mean +/- s.e.mean) min, reaching 24.1
      +/- 4.7 and 15.1 +/- 3.2 pmol 1(-1) and respective terminal half-lives were 2.2
      +/- 0.1 and 2.0 +/- 0.1 h. Based on the area under the concentration-time-curve,
      the bioequivalent IN/oral ratio was 1:16. 3. As judged by changes in urine flow
      rate and osmolality after IN or oral (100, 200 or 400 micrograms) DDAVP,
      antidiuretic activity increased rapidly during the second hour and peaked at 4 h.
      The antidiuresis duration and magnitude correlated with the oral dose (P < 0.001
      and < 0.05 respectively), and was least following 100 micrograms (P < 0.01 vs 200
      or 400 micrograms). Increasing the dose from 200 to 400 micrograms did not
      increase maximal antidiuretic activity significantly, but there was a trend
      towards a longer duration of action (P = 0.076). 4. During the 1-year prospective
      study with oral DDAVP 300-600 micrograms per day in two to three doses, stable
      and satisfactory antidiuresis (comparable with that on previous IN therapy) was
      maintained; tablets were well-tolerated and no side-effect warranted drug
      withdrawal. 5. These findings suggest that the 100 and 200 micrograms
      preparations of oral DDAVP are adequate for the long-term control of central
      diabetes insipidus in our population, and that the 400 micrograms preparation may
      have a role if the frequency of administration is to be reduced.

PMID- 8877031
TI  - Expression of CYP3A4, CYP3A5 and CYP3A7 in human duodenal tissue.
AB  - The essential role of cytochrome P450 3A4 (CYP3A4) in human small intestine is
      well established, and CYP3A5 seems also to be present in most subjects. However,
      the role of CYP3A7 in the small intestine remains poorly characterized. We have
      therefore studied the expression of these CYP3A enzymes in the duodenal tissue
      from 19 patients, using a specific RT-PCR (reverse transcriptase-polymerase chain
      reaction) method. CYP3A4 and CYP3A5 were present at the mRNA level in the
      duodenum of 18 and 19 of the 19 patients studied, respectively. In contrast, mRNA
      for CYP3A7 was not found in the duodenum in any of the patients. These findings
      strongly suggest that, unlike CYP3A4 and CYP3A5, CYP3A7 is not expressed in human
      duodenum.

PMID- 8877032
TI  - Variable contribution of CYP2D6 to the N-dealkylation of S-(-)-propranolol by
      human liver microsomes.
AB  - Recombinant cDNA expression systems for CYP2D6 have been shown to have
      significant catalytic activity with respect to the N-dealkylation of propranolol.
      However, the involvement of CYP2D6 in this reaction in human liver is
      inconclusive. We have re-evaluated the role of CYP2D6 in the dealkylation of S-(
      )-propranolol using a bank of 10 human livers characterized for their specific
      CYP2D6 and CYP1A2 activities, the latter enzyme being known to be involved
      substantially in the formation of N-desisopropylpropranolol. Using quinidine (1
      microM) or LKM-1 antibodies as selective inhibitors of CYP2D6, the contribution
      of this enzyme to net N-desisopropylation of S-(-)-propranolol (10 microM) by
      microsomes from the range of livers was found to vary from nil (poor metabolizer
      genotype) to 60%. N-desisopropylpropranolol formation inhibitable by quinidine
      was highly correlated with specific CYP2D6 activity, as measured by the alpha
      hydroxylation of metoprolol (rs = 0.90; P < 0.001). The two livers with the
      highest proportion of CYP2D6-mediated N-dealkylation had relatively high ratios
      of specific CYP2D6 to CYP1A2 activity. These findings emphasize that data
      obtained using microsomes from single human livers or pooled microsomes from
      several livers may be misleading inasmuch as the relative contribution of
      different isoenzymes to the same metabolic reaction may show considerable between
      subject variation.

PMID- 8877033
TI  - Influence of liver cirrhosis on sertraline pharmacokinetics.
AB  - Sertraline is a serotonin reuptake inhibitor. The enhancement of serotoninergic
      transmission is associated with antidepressant activity. In order to determine
      the pharmacokinetics of sertraline in patients with chronic stable hepatic
      insufficiency, 10 patients were matched (age, weight, sex) with 10 healthy
      subjects in an open study. Each participant received a single capsule containing
      the equivalent of 100 mg sertraline base. Blood samples were taken during 264 h
      after administration for measurement of plasma concentrations of sertraline. The
      results confirm that the oral clearance of sertraline is reduced with a 1.7-fold
      increase in Cmax and a significant prolongation in elimination half-life in
      hepatically impaired patients.

PMID- 8877034
TI  - Drug-induced QT interval prolongation.

PMID- 8877035
TI  - Cross over trials.

PMID- 8877036
TI  - Parenteral administration of 8-methoxypsoralen.

PMID- 8877037
TI  - An ethicist's commentary on the case of the veterinarian who euthanized an animal
      thinking that he had received owner permission.

PMID- 8877038
TI  - Good production practices in the feedlot.

PMID- 8877039
TI  - Nonsteroidal anti-inflammatory analgesics in pain management in dogs and cats.

PMID- 8877040
TI  - Postoperative use of analgesics in dogs and cats by Canadian veterinarians.
AB  - Four hundred and seventeen Canadian veterinarians were surveyed to determine
      their postoperative use of analgesics in dogs and cats following 6 surgical
      procedures, and to determine their opinions toward pain perception and perceived
      complications associated with the postoperative use of potent opioid analgesics.
      Three hundred and seventeen (76%) returned the questionnaire. The percentage of
      animals receiving analgesics postoperatively ranged from 84% of dogs and 70% of
      cats following orthopedic surgery to 10% of dogs and 9% of cats following
      castration. In general, with the exception of orthopedic surgery, roughly equal
      percentages of dogs and cats received postoperative analgesics. Opioids were used
      almost exclusively to provide postoperative analgesia, with butorphanol the most
      commonly administered drug to both dogs and cats. Analgesics were usually
      administered either once or twice postoperatively. With regard to the
      administration of potent opioid agonists, the 3 major concerns included
      respiratory depression, bradycardia, and sedation in dogs, and excitement,
      respiratory depression, and bradycardia in cats. Seventy-seven percent of
      veterinarians considered their knowledge of issues related to the recognition and
      control of postoperative pain to be inadequate. Experience in practice is
      currently the major source of knowledge, with undergraduate veterinary school and
      research articles in journals ranked as the least important sources. Lectures or
      seminars delivered at the regional level were the preferred format for continuing
      education.

PMID- 8877041
TI  - Factors influencing the postoperative use of analgesics in dogs and cats by
      Canadian veterinarians.
AB  - Four hundred and seventeen Canadian veterinarians were surveyed to determine
      their postoperative use of analgesics in dogs and cats following 6 categories of
      surgeries, and their opinion toward pain perception and perceived complications
      associated with the postoperative use of potent opioid analgesics. Three hundred
      and seventeen (76%) returned the questionnaire. An analgesic user was defined as
      a veterinarian who administers analgesics to at least 50% of dogs or 50% of cats
      following abdominal surgery, excluding ovariohysterectomy. The veterinarians
      responding exhibited a bimodal distribution of analgesic use, with 49.5% being
      defined as analgesic users. These veterinarians tended to use analgesics in 100%
      of animals following abdominal surgery. Veterinarians defined as analgesic
      nonusers rarely used postoperative analgesics following any abdominal surgery.
      Pain perception was defined as the average of pain rankings (on a scale of 1 to
      10) following abdominal surgery, or the value for dogs or cats if the
      veterinarian worked with only 1 of the 2 species. Maximum concern about the risks
      associated with the postoperative use of potent opioid agonists was defined as
      the highest ranking assigned to any of the 7 risks evaluated in either dogs or
      cats. Logistic regression analysis identified the pain perception score and the
      maximum concern regarding the use of potent opioid agonists in the postoperative
      period as the 2 factors that distinguished analgesic users from analgesic
      nonusers. This model correctly classified 68% of veterinarians as analgesic users
      or nonusers. Linear regression analysis identified gender and the presence of an
      animal health technologist in the practice as the 2 factors that influenced pain
      perception by veterinarians. Linear regression analysis identified working with
      an animal health technologist, graduation within the past 10 years, and
      attendance at continuing education as factors that influenced maximum concern
      about the postoperative use of opioid agonists.

PMID- 8877042
TI  - Papillomatosis of a farmed black cod in British Columbia.

PMID- 8877043
TI  - A comparison of ketorolac with flunixin, butorphanol, and oxymorphone in
      controlling postoperative pain in dogs.
AB  - Ketorolac tromethamine, a nonsteroidal anti-inflammatory analgesic, was compared
      with flunixin and butorphanol for its analgesic efficacy and potential side
      effects after laparotomy or shoulder arthrotomy in dogs. Sixty-four dogs were
      randomly assigned to receive butorphanol 0.4 mg/kg body weight (BW) (n = 21),
      flunixin 1.0 mg/kg BW (n = 21), or ketorolac 0.5 mg/kg BW (n = 22), in a double
      blind fashion. The analgesic efficacy was rated from 1 to 4 (1 = inadequate, 4 =
      excellent) for each dog. The average scores after laparotomy were ketorolac, 3.4;
      flunixin, 2.7; and butorphanol, 1.6. After shoulder arthrotomy, the average
      scores were ketorolac, 3.5; flunixin, 3.0; and butorphanol, 1.4 (5/11 dogs). As
      butorphanol was unable to control pain after shoulder arthrotomy, oxymorphone,
      0.05 mg/kg BW, replaced butorphanol in a subsequent group of dogs and had a score
      of 2.0 (6/11 dogs). Serum alanine aminotransferase and creatinine were
      significantly elevated above baseline at 24 hours postoperatively in dogs
      receiving flunixin. One dog in each group developed melena or hematochezia. One
      dog receiving ketorolac had histological evidence of gastric ulceration. We
      concluded that ketorolac is a good analgesic for postoperative pain in dogs.

PMID- 8877044
TI  - Clinical pathology interpretation.

PMID- 8877045
TI  - Breast cancer and oral contraceptives--the evidence so far.

PMID- 8877046
TI  - Smoking habits and risk of cancers other than lung cancer: 28 years' follow-up of
      26,000 Norwegian men and women.
AB  - The impact of tobacco smoking on lung cancer risk has been investigated
      thoroughly since the 1950s, but other types of cancer also have been associated
      with smoking. In the present study, the aim was to explore the variation in risk
      connected with cigarette, cigar, and pipe smoking of suspected smoking-associated
      cancers other than lung cancer. Data were obtained from a survey of a random
      sample of the Norwegian population. A self-administered mailed questionnaire,
      which included questions about smoking habits, was completed by 26,000 men and
      women in 1965 (response rate: 76 percent). The cohort was followed from 1966
      through 1993, including registration of all incident cancer cases. A dose
      response relationship of cigarette smoking to the risk of urinary bladder cancer
      and cancers of the upper digestive and respiratory tract was observed. For the
      latter forms of cancer, a dose-response relationship of pipe smoking also was
      observed. In cancer of the pancreas, a stronger association between cigarette
      smoking and cancer risk was observed when the analysis was confined to
      histologically confirmed cases only. Current cigarette smokers at baseline had a
      significantly higher risk of cervical cancer than those who never smoked
      cigarettes. In cancers of the stomach, colon, rectum, breast, corpus uteri,
      ovary, and prostate, and in leukemia, no association between smoking and cancer
      risk was observed.

PMID- 8877047
TI  - Lifestyle changes during adolescence and risk of breast cancer: an ecologic study
      of the effect of World War II in Norway.
AB  - There are biologic reasons to believe that the period between the larche and the
      first full-term pregnancy is a particularly sensitive period in a woman's life
      regarding the development of breast cancer. In this ecologic study, data provided
      by the Norwegian Cancer Registry were analyzed to compare risk of breast cancer
      among women who experienced this sensitive period before, during, or after World
      War II. An ordinary age-cohort model and a model where the cohort was described
      by exposure by calendar period and sensitivity to this exposure at different
      ages, were fitted to the data. The incidence of breast cancer was lower than
      expected among women who experienced puberty during the war. The estimated
      configuration of the exposure variable showed an increase in exposure up to the
      start of WWII to twice the level in 1916, dropped by 13 percent during the war,
      and increased again after the war. The level in 1975 was approximately 2.7 times
      higher than the level in 1916. The results indicate that one or more lifestyle
      factors that changed among adolescent women during the war, influenced their risk
      of breast cancer. Dietary intake of energy, fat, meat, milk, fish, fresh
      vegetables, and potatoes, in addition to physical activity level and height, are
      important factors to consider in relation to breast cancer risk.

PMID- 8877048
TI  - Progestogen-only oral contraceptives and risk of breast cancer in New Zealand.
AB  - Little is known about the influence of progestogen-only oral contraceptives on a
      woman's risk of breast cancer. This issue was examined in a national population
      based case-control study in New Zealand. A total of 891 women aged 25 to 54 years
      with a first diagnosis of breast cancer and 1,864 control subjects, randomly
      selected from the electoral rolls, were interviewed. Use of progestogen-only
      pills was reported by 8.7 percent of all control subjects (and by 17.3 percent of
      those aged 25 to 34 years). The relative risk (RR) of breast cancer in women who
      had ever used progestogen-only pills was estimated to be 1.1 (95 percent
      confidence interval [CI] = 0.73-1.5). In women aged 25 to 34 years, the RR was
      2.3 (CI = 1.2-4.3). Women who had started using progestogen-only pills within the
      last 10 years were at increased risk of breast cancer (RR = 1.6, CI = 1.0-2.4),
      whereas those who had first used them earlier were at significantly reduced risk
      (RR = 0.44, CI = 0.22-0.90). These findings are similar to results for depot
      medroxyprogesterone acetate, and a possible analogy with the influence of
      pregnancy is also suggested.

PMID- 8877049
TI  - Cervical cancer screening in Tamilnadu, India: a feasibility study of training
      the village health nurse.
AB  - Uterine cervical cancer is the most common malignancy among females in developing
      countries, including India. The success of cervical cancer screening programs in
      North America and Western Europe has been the result of centralized cervical
      cytology screening. This is not possible in the villages (n = 17,000) of
      Tamilnadu where 58 percent of females in rural areas are illiterate, health
      infrastructure is mediocre, and cervical cytology is unknown. The present study
      was undertaken to examine if the village health nurse (VHN) could be trained
      quickly to identify a cervical abnormality by visual inspection so that we could
      'down stage' the cancer to earlier stages, more amenable to treatment. VHNs also
      would be trained to take an adequate Pap smear. A total of 101 VHNs were trained
      in batches and returned to their villages. Within two years, 6,459 eligible women
      in the study area were screened. The agreement between the gynecologists and the
      VHNs in identifying cancer among those with abnormal cervix was 95 percent, and
      80 percent of the Pap smears taken by VHNs were adequate by WHO criteria, making
      the feasibility study highly successful.

PMID- 8877051
TI  - Maternal risk of breast cancer following multiple births: a nationwide study in
      Sweden.
AB  - The association between multiple births and subsequent maternal breast cancer
      risk was explored in a nested case-control study in Sweden encompassing 19,368
      parous women with breast cancer diagnosed up to age 65 years, and 100,459 parous
      controls. Among cases and controls, there were 329 and 2,031 women, respectively,
      with a history of at least one live multiple birth. Compared with singleton
      mothers, breast cancer risk was 12 percent lower (odds ratio = 0.88, 95 percent
      confidence interval = 0.78-0.99) in women who had had a multiple birth. After
      stratification for age at diagnosis, evidence of a significant inverse
      association was found only in women aged 54 years or younger. Birth order of the
      multiple pregnancy had no apparent risk-modifying effect. Age at earliest
      multiple birth was unrelated to breast cancer risk. The inverse association
      between twinning and breast cancer risk may reflect protective physiological
      features of twin pregnancies. Further research is needed to investigate the role,
      if any, of increased levels of steroid hormone-binding globulins in mothers of
      twins and the proposed inhibitory effects of human chorionic gonadotropin and
      alpha-fetoprotein, both of which are increased during multiple gestations, on
      breast carcinogenesis. Breast feeding patterns in mothers of twins also may
      modify their risk of developing breast cancer.

PMID- 8877050
TI  - Recent oral contraceptive use and risk of breast cancer (United States)
AB  - We examined the association between recent oral contraceptive (OC) use and the
      risk of breast cancer in data from a large population-based case-control study in
      the United States. Cases (n = 6,751) were women less than 75 years old who had
      breast cancer identified from statewide tumor registries in Wisconsin,
      Massachusetts, Maine, and New Hampshire. Controls (n = 9,311) were selected
      randomly from lists of licensed drivers (if aged under 65 years) and from lists
      of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use,
      reproductive experiences, and family and medical history was obtained by
      telephone interview. After adjustment for parity, age at first delivery, and
      other risk factors, women who had ever used OCs were at similar risk of breast
      cancer as never-users (relative risk [RR] = 1.1, 95 percent confidence interval
      [CI] = 1.0-1.2). Total duration of use also was not related to risk. There was a
      suggestion that more recent use was associated with an increased risk of breast
      cancer; use less than two years ago was associated with an RR of 1.3 (CI = 0.9
      1.9). However, only among women aged 35 to 45 years at diagnosis was the increase
      in risk among recent users statistically significantly elevated (RR = 2.0, CI =
      1.1-3.9). Use prior to the first pregnancy or among nulliparous women was not
      associated with increased risk. Among recent users of OCs, the risk associated
      with use was greatest among non-obese women, e.g., among women with body mass
      index (kg/m2) less than 20.4, RR = 1.7, CI = 1.1-2.8. While these results suggest
      that, in general, breast cancer risk is not increased substantially among women
      who have used OCs, they also are consistent with a slight increased risk among
      subgroups of recent users.

PMID- 8877052
TI  - Laterality of breast cancer in the United States.
AB  - Breast cancer laterality of over 250,000 cases from the Surveillance,
      Epidemiology, and End Results (SEER) program in the United States was studied in
      relation to gender, race, tumor stage, histology, age at diagnosis, year of
      diagnosis, estrogen receptor status, and marital status. The data, which include
      all invasive and in situ breast cancer cases in the SEER program during the years
      1973-92, confirm results from other studies of an overall five percent excess of
      left-sided disease in women. The excess occurs for all races and stages of
      disease, and for invasive disease, the excess increases with age. There was no
      significant variation in the laterality of invasive disease over time, though for
      in situ tumors, the left-sided excess was significantly greater during the years
      1978-82 than in other periods. No excess of left-sided breast cancer was observed
      among men. There is no evidence that detection bias plays a major role, and
      although the left breast is slightly larger, on average, than the right, there is
      little evidence that breast size is associated with breast cancer risk. The
      reason for the left-sided excess among women remains unclear.

PMID- 8877053
TI  - Risk-adjusted cancer-incidence rates (United States).
AB  - A risk-adjusted method is proposed for estimating cancer incidence rates from
      data collected by the Surveillance, Epidemiology, and End Results (SEER) program
      of the US National Cancer Institute. Unlike the conventional incidence-rate
      estimates reported by SEER, this method considers only the first primary cancer,
      and adjusts for population-based cancer prevalence, as well as for surgical
      procedures which remove an individual from risk of developing a given cancer.
      Thus, risk-adjusted incidence-rates more accurately reflect the average cancer
      risk for individuals in the cancer-free, at-risk population. The results of the
      analysis indicate that, in general, incidence-rate estimates are fairly similar
      between the conventional and risk-adjusted methods. However, this is not the case
      for certain cancer sites which may have: (i) a high number of subsequent primary
      cancers (e.g., melanomas-skin); (ii) a high cancer prevalence proportion (e.g.,
      prostate cancer); (iii) a high number of subsequent primary cancers and
      prevalence proportion (e.g., female breast); or (iv) a high prevalence of removal
      of the organ in question (e.g., cervical and uterine cancers). For example, by
      applying the risk-adjusted incidence method for in situ and invasive cervical
      cancer, we found that in the period 1990-92 the age-adjusted incidence-rate
      estimate increased from 57.8 to 66.3 (15 percent) per 100,000 person-years; the
      greatest increase in the incidence-rate estimate occurred for women aged 65 to 69
      years, from 40.1 to 63.2 (58 percent) per 100,000 person-years; and the lifetime
      risk of developing cervical cancer increased from 4.6 (1 in 22) to 5.5 (1 in 18)
      percent.

PMID- 8877055
TI  - Consensus conference: smoking and prostate cancer.

PMID- 8877054
TI  - Big babies and infant leukemia: a role for insulin-like growth factor-1?
AB  - Several epidemiologic studies have demonstrated that high birthweight is
      associated with an increased risk of infant leukemia; however, the reason for
      this relationship is unclear. Biologic data demonstrate that birth weight is
      correlated positively with circulating levels of insulin-like growth factor-1
      (IGF-1). IGF-1 is important in blood formation and regulation and has been shown
      to stimulate the growth of both myeloid and lymphoid cells in culture. Since
      infants who develop leukemia are likely to have had at least one transforming
      event occur in utero, we hypothesize that high levels of IGF-1 may both produce a
      larger baby and contribute to leukemogenesis.

PMID- 8877056
TI  - Fruit and vegetable consumption and cancer mortality in the Caerphilly Study.
AB  - We investigated whether the consumption of fruit and vegetables lowered cancer
      mortality in a cohort of 2112 Welsh men ages 45-69 years (The Caerphilly Study),
      which was followed-up for 13.8 years. At baseline (between 1979 and 1983),
      participants completed a 56-item food frequency questionnaire from which the
      consumption of fruit and vegetables was calculated. Relative risks (RR) were
      estimated with Cox proportional hazard analysis, with death from various types of
      cancer as a dependent variable, and fruit, vegetables, vitamin C, beta-carotene,
      dietary fiber, and potential confounders as independent variables. Mean
      consumption of vegetables and fruit at baseline was 118 g/day and 83 g/day,
      respectively. During follow-up 114 men died from cancer, including 51 men who
      died from respiratory tract cancer and 45 men who died from digestive tract
      cancer. Fruit consumption and the intake of dietary fiber were inversely related
      to respiratory tract cancer, but after adjustment for potential confounders
      including age, smoking, and social class, the association with fruit consumption
      became nonsignificant. Vegetable and fruit consumption was, independently from
      other risk factors, inversely related to mortality from cancer of the digestive
      tract (P for trend = 0.021), mainly due to an inverse association with fruit
      consumption (RR for the highest quartile versus the lowest was 0.3; 95% CI, 0.1
      0.8). Vitamin C, beta-carotene, and dietary fiber were not significantly
      associated with cancers of the digestive tract. Vegetable and fruit consumption
      was also inversely related to all-cause cancer mortality, and the strongest
      association was observed for fruit consumption (RR in the highest versus lowest
      quartile was 0.5; 95% CI, 0.3-1.0). Consumption of vegetables and particularly
      the consumption of fruit could considerably lower the risk of dying from cancer
      in middle-aged men.

PMID- 8877057
TI  - Dietary nitrosodimethylamine and the risk of lung cancer: a case-control study
      from Uruguay.
AB  - Evidence from animal studies indicates that various N-nitroso compounds are
      carcinogenic. We investigated whether consumption of nitrosodimethylamine (NDMA)
      and foods and beverages containing NDMA are carcinogenic for the lung. In a
      hospital-based case-control study in Uruguay, dietary intake of NDMA and its food
      sources was measured in 320 cases of lung cancer and 320 controls afflicted with
      diseases not related with tobacco use and diet. After adjusting for tobacco
      smoking and total energy intake, NDMA displayed a significant dose-response
      pattern, with a 3-fold increase in risk for the higher category of intake. The
      risks were slightly more elevated for adenocarcinoma of the lung. Also, salted
      meat consumption and beer intake were associated with an increased risk of lung
      cancer.

PMID- 8877058
TI  - Effects of CYP2D6 activity and tobacco on larynx cancer risk.
AB  - The genetically determined capacity of the cytochrome P450 CYP2D6 is suspected to
      be involved in the activation of tobacco carcinogens. From a multicentric case
      control study carried out to analyze the interaction between host and
      environmental factors on tobacco-related cancers, we reported recently that the
      effect of tobacco on lung cancer risk rose with increasing CYP2D6 activity, and
      the effect of CYP2D6 activity rose with increasing tobacco consumption. The aim
      of the present report was to investigate whether results on lung cancer could be
      observed for larynx cancer, from a study on 140 cases and 157 controls. A weak
      interaction between increasing levels of both CYP2D6 activity and average daily
      consumption of tobacco was found (P = 0.12). The only significant interaction
      between these two factors was observed when CYP2D6 activity was considered with
      the two conventional phenotypes (P < 0.05). A dose-response effect of tobacco on
      larynx cancer risk was found only among one-third of the smokers with the highest
      level of CYP2D6 activity, and CYP2D6 was a risk factor only among heavy smokers.
      The highest risk for larynx cancer was then observed among smokers having both
      the highest levels of CYP2D6 activity and daily consumption of tobacco. The
      interaction between CYP2D6 activity and tobacco was weaker for larynx cancer than
      that reported previously for lung cancer. However, the similarities in the
      results found for these two cancers, i.e., a greater effect of tobacco among
      smokers with the highest CYP2D6 activity, reinforce the hypothesis that this
      activity could modify the effect of tobacco on cancer risk.

PMID- 8877059
TI  - Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility.
AB  - We conducted a case-control study of 207 lung cancer patients and 283 controls to
      estimate the association of the MspI polymorphism in the cytochrome P450 CYP1A1
      gene with lung cancer. The analysis of the CYP1A1 gene polymorphism was performed
      by RFLP analysis of PCR-amplified DNA. The association of the CYP1A1 polymorphism
      with lung cancer was assessed by logistic regression using the generalized
      additive modeling technique to adjust for race, education, smoking status, pack
      years, time since quitting smoking, asbestos exposures, and family cancer
      history. The frequencies of the MspI homozygote and heterozygote variant
      genotypes of CYP1A1 were 1% and 17%, respectively, in both lung cancer patients
      and controls. A significant association was found between the combined
      heterozygous and homozygous MspI variant of the CYP1A1 gene and lung cancer; the
      estimated odds ratio was 2.08 (95% confidence interval, 1.15-3.73). The
      association remained significant when we excluded the homozygous MspI variant
      individuals, the non-Caucasians, or the long-time tobacco quitters, and it was
      not modified by gender or cumulative cigarette consumption. In a specific
      histological cell type analysis, a positive association was found for each
      subtype of lung cancer, with no appreciable difference between cell types. In
      summary, our study demonstrated that the MspI variant CYP1A1 genotype is
      significantly associated with an increased risk of lung cancer among Caucasians
      with the odds ratio approximately, equivalent to 2 after controlling for
      important confounding factors. These results are similar to those obtained from
      reanalysis of published data on the combined CYP1A1 genotypes in a Japanese
      population (combined odds ratio, 1.95; 95% confidence interval, 1.17-3.28).
      Moreover, the elevated risk is noted in heterozygotes, i.e., individuals who
      carry only one copy of the variant gene.

PMID- 8877060
TI  - Cytochrome P4501A2: enzyme induction and genetic control in determining 4
      aminobiphenyl-hemoglobin adduct levels.
AB  - Cytochrome P4501A2 (CYP1A2) activity may be related to bladder cancer risk
      through metabolic activation of aromatic amines, such as 4-aminobiphenyl (ABP),
      to reactive intermediates that can form DNA and hemoglobin (Hb) adducts. In the
      context of a study on smoking and bladder cancer risk, 97 healthy male volunteers
      were investigated. CYP1A2-dependent N-oxidation activity was measured using a
      molar ratio of urinary caffeine metabolites [(paraxanthine + 1,7-dimethyluric
      acid)/caffeine] obtained between the fourth and fifth h after drinking a
      standardized cup of coffee. N-Oxidation activity was induced by blond tobacco
      smoke, meat consumption the dinner before the test, or more than four cups of
      coffee a day. The regular use of medication appeared associated with a decrease
      in N-oxidation levels. Age and alcohol consumption were not related with CYP1A2
      activity. A polymorphic distribution of the CYP1A2 and N-acetyltransferase-2
      (determined by the caffeine metabolite ratio 5-acetylamino-6-formylamino-3
      methyluracil:1-methylxanthine) phenotypes was examined in relation to
      susceptibility to ABP-Hb adduct formation. Rapid oxidizers and subjects with the
      combined slow acetylator-rapid oxidizer phenotype showed the highest ABP-Hb
      adduct levels at a low smoking dose. Blond tobacco smokers exhibited higher
      adduct levels compared with black tobacco smokers, after adjustment for the
      quantity of cigarettes smoked. At the highest levels of smoking exposure, no
      major difference in ABP-Hb adduct levels was found among the different
      combinations of CYP1A2 and N-acetyltransferase-2 phenotypes. In a subset of only
      45 available samples, no association was seen between the ABP-Hb adduct levels
      and the glutathione S-transferase M1 genotype.

PMID- 8877061
TI  - Differential patterns of serum biomarkers of immune activation in human T-cell
      lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and
      adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with
      differing patterns of immune dysfunction. Biomarkers of immune activation may
      correlate with perturbations of immune function associated with these diseases.
      We conducted a pilot cross-sectional study to assess four candidate biomarkers of
      immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine
      levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus
      type I (HTL V-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+)
      individuals, and ATL and HAM/TSP patients previously enrolled in
      seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin,
      neopterin, and kynurenine were significantly elevated among ATL patients compared
      to the other study groups. Mean tryptophan levels were significantly lower among
      ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant
      differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups.
      Among HAM/TSP patients, a significant association was found between elevated
      neopterin levels and symptoms of less than 4 years duration. In Cox proportional
      hazards regression modeling, neopterin and tryptophan were found to be
      independent predictors of survival among ATL patients. This study demonstrates a
      differential pattern of biomarkers of immune activation among ATL and HAM/TSP
      patients compared to HTLV-I- and HTLV-I+ individuals. Neopterin and tryptophan
      may be useful clinical indicators of disease severity and prognosis among HAM/TSP
      and ATL patients.

PMID- 8877062
TI  - Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast
      tissues.
AB  - The etiology of the majority of human breast cancers is unknown; however,
      oxidative stress and lipid peroxidation have been suggested to play a role in
      breast carcinogenesis. To address this possibility, DNA adducts induced by
      malondialdehyde (MDA), an end product of lipid peroxidation, were analyzed in
      surgical specimens of normal breast tissues of 51 breast cancer patients using
      the nuclease P1-enhanced version of the 32P-postlabeling assay. Normal breast
      tissue samples from 28 noncancer patients receiving reduction mammoplasty served
      as controls. Two previously characterized putative MDA-deoxyadenosine (dA) and
      one MDA-deoxyguanosine adduct were detected in all tissue samples examined.
      Normal breast tissues from cancer patients exhibited significantly higher levels
      of the putative MDA adducts [median (42.5) and range (2.2-202.8) of relative
      adduct labeling x 10(9) values] than those found in noncancer controls (median,
      15.67; range, 2.4-382.1; P = 0.0001, Mann-Whitney U test). Ten of the 51 cancer
      patients and 1 of the 28 controls were found to contain the putative MDA adducts
      at the level of > 1/10(7) nucleotides, a frequency comparable to that found in
      human liver. Age and body mass did not significantly influence the levels of
      these adducts. However, the presence of a previously detected benzo(a)pyrene-like
      DNA adduct in the breast tissues was associated with higher levels of the
      putative MDA-dA adducts in cancer patients (P = 0.012). The level of the putative
      MDA-dA adducts was significantly lower in smokers and former smokers compared to
      nonsmokers among cases after adjusting for age, body mass index, and status of
      the benzo(a)pyrene-like adduct (P = 0.009). Tumor tissues (n = 11) displayed
      significantly lower levels of the putative MDA adducts (median, 10.2; range, 5.3
      20.6) than their corresponding normal adjacent tissues (median, 25.5; range, 10.5
      138; P < 0.01). These findings provide evidence that lipid peroxidation products
      can accumulate in human breast tissues and reach relatively high levels in the
      breast tissues of women with breast cancer. There seems to be an interaction
      between these endogenous DNA modifications and carcinogen exposure-induced DNA
      adducts. Detection and quantitation of the putative MDA-DNA adducts may
      potentially be a useful tool in the understanding of breast cancer etiology.

PMID- 8877063
TI  - The quantitation of metabolites of quercetin flavonols in human urine.
AB  - The flavonoid quercetin, or its metabolites, inhibit chemical carcinogenesis in
      rodents and may have a role in the prevention of human cancers. Quercetin
      exposure in human populations results from the dietary intake of various plant
      foods; high concentrations of quercetin are found in apples, onions, tea, and red
      wine. Determination of the relationship between dietary intake and cancer risk
      depends on the characterization of quercetin intake. The development and use of
      biomarkers for quercetin intake may provide a basis for the objective
      classification of this exposure. One possible biomarker is metabolic products of
      quercetin. We report the development of a high-performance liquid chromatography
      (HPLC)-based assay for quantitation of quercetin metabolites in human urine. The
      metabolites include 3,4-dihydroxyphenylacetic acid (homoprotocatechuic acid),
      metahydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid
      (homovanillic acid). The assay has only two major steps, ether extraction and
      HPLC analysis, and is suitable for analysis of large sample numbers. Analytical
      characteristics of the assay include a sensitivity of less than 1 microgram,
      precision with coefficients of variation < 10%, and metabolite recoveries > 90%.
      The mean concentrations of 3,4-dihydroxyphenylacetic acid,
      metahydroxyphenylacetic acid, and homovanillic acid in two human urine samples
      are approximately 0.7, 4.8, and 2.8 micrograms/ml, respectively. The
      identification of each metabolite is confirmed by HPLC, UV absorbance scans, and
      gas chromatography-mass spectrometry analysis. These results verify the
      occurrence of quercetin metabolites in human urine and the feasibility of
      quercetin metabolite quantitation, by the assay described herein, for
      epidemiological studies. Development of the analytical procedure is an essential
      first step for validation of the metabolites as biomarkers of quercetin intake.

PMID- 8877064
TI  - Validation of self-reported breast and cervical cancer screening tests among low
      income minority women.
AB  - The objective of the Forsyth County Cancer Screening Project is to assess
      barriers to breast and cervical cancer screening among low-income women and to
      develop an educational program to address these barriers. To properly assess the
      barriers, it was first necessary to determine if self-reported rates of breast
      and cervical cancer screening were accurate. All women who participated in the
      baseline survey (n = 555) were asked to provide information regarding if, where,
      and when they had obtained mammograms and Pap smears. Identified health care
      facilities were then contacted to verify this information. Approximately 80% of
      responses were verified for at least one of the exams with the information
      provided. For mammography, 77% of self-reports were correct, whereas 67% of self
      reports of Pap smear screening were correct (kappa = 0.54 and 0.15,
      respectively). For both tests, women thought they had received them more recently
      than they actually had, by an average of 3 months for mammography and 23 months
      for Pap smears. Using validated reports of screening did not substantially change
      identified predictors of screening for mammography. For Pap smear screening,
      however, most of the identified predictors of screening became nonsignificant
      when medical chart reports were used instead of self-reports, suggesting that
      caution should be used in relying on self-reports to design programs to improve
      cervical cancer screening practices.

PMID- 8877065
TI  - Measurement of urinary estrogen metabolites using a monoclonal enzyme-linked
      immunoassay kit: assay performance and feasibility for epidemiological studies.
AB  - We evaluated an enzyme-linked immunoassay kit (Estramet 2/16) for the measurement
      of 2-hydroxyestrone (2-OH E1) and 16-alpha hydroxyestrone (16 alpha-OH E1), major
      metabolites of estradiol. Urine samples from 14 healthy premenopausal women on
      days 1, 8, 15, and 22 of their menstrual cycle were assayed along with standards,
      kit controls, and in-house controls. The intra-assay percentage CVs of 2-OH E1,
      16 alpha-OH E1, and the 2-OH E1: 16 alpha-OH E1 ratio were 6.8, 7.4, and 1.8,
      respectively; the interassay percentage CVs were 15.3, 30.7, and 23.3,
      respectively. The assay linearity was between 0 and 40 ng/ml. The mean 2-OH E1:16
      alpha-OH E1 ratio was relatively constant throughout the day, but it increased by
      around 50% between the follicular and luteal portions of the menstrual cycle.
      Individual reagent kits within each lot for 16 alpha-OH E1 were stable for 2
      weeks. There was considerable lot-to-lot variation over a 5-month period. In lots
      used during the last 2 months of the study, values of 2-OH E1 from in-house
      controls increased by 30-50%, and those of 16 alpha-OH E1 by 50-100%, relative to
      values obtained initially on the same samples. Depending on the lot, the ratio of
      the two metabolites ranged from 2 to 5.5. These data suggest that the assay is
      useful for studies where samples can be assayed with the same kit lot over a
      period of not more than 2 weeks, but that it is not now suitable for studies that
      extend over a long enough period of time so that multiple kit lots are required.

PMID- 8877066
TI  - Epidemiological studies on brassica vegetables and cancer risk.
AB  - This paper gives an overview of the epidemiological data concerning the cancer
      preventive effect of brassica vegetables, including cabbage, kale, broccoli,
      Brussels sprouts, and cauliflower. The protective effect of brassicas against
      cancer may be due to their relatively high content of glucosinolates. Certain
      hydrolysis products of glucosinolates have shown anticarcinogenic properties. The
      results of 7 cohort studies and 87 case-control studies on the association
      between brassica consumption and cancer risk are summarized. The cohort studies
      showed inverse associations between the consumption of cabbage, cauliflower, and
      broccoli and risk of lung cancer; between the consumption of brassicas and risk
      of stomach cancer; between broccoli consumption and risk of all cancers taken
      together; and between brassica consumption and the occurrence of second primary
      cancers. Of the case-control studies, 67% showed an inverse association between
      consumption of total brassica vegetables and risk of cancer at various sites. For
      cabbage, broccoli, cauliflower, and Brussels sprouts, these percentages were 70,
      56, 67, and 29%, respectively. Although the measured effects might have been
      distorted by various types of bias, it is concluded that a high consumption of
      brassica vegetables is associated with a decreased risk of cancer. This
      association appears to be most consistent for lung, stomach, colon, and rectal
      cancer and least consistent for prostatic, endometrial, and ovarian cancer. It is
      not yet possible to resolve whether associations are to be attributed to brassica
      vegetables per se or to vegetables in general. Further epidemiological research
      should separate the anticarcinogenic effect of brassica vegetables from the
      effect of vegetables in general.

PMID- 8877067
TI  - Alaska Native cancer update: incidence rates 1989-1993.
AB  - Five-year average annual age-adjusted cancer incidence rates for Alaska Natives
      (Eskimos, Indians, and Aleuts) for the most recent period (1989-1993) are
      compared to rates of 20 years earlier. Rates for all cancers combined increased
      28 and 25% in men and women, respectively, during the 25-year interval. Increases
      were seen in men in cancers of the lung, prostate, and colon and in women for
      cancers of the lung, breast, and corpus uteri. Rates are also compared to data
      from the the National Cancer Institute's Surveillance, Epidemiology, and End
      Results (SEER) program for United States whites. Rates for all cancers combined
      in Alaska Native women are now similar to those of United States whites, whereas
      rates in Alaska Native men are lower than the United States, but only 10% lower.
      Significant site-specific differences previously reported between Alaska Natives
      and United States whites persist.

PMID- 8877068
TI  - Measurement of organochlorine levels in postprandial serum or in blood collected
      in serum separator tubes.
AB  - Whether organochlorine blood levels in fasting and postprandial specimens provide
      equivalent measures of exposure and the extent to which collecting blood in tubes
      containing material to separate serum and blood cells corrupts the specimen are
      unclear. In this paper, we present data from two studies that address both of
      these issues. In the first study, 27 women provided fasting blood in plain,
      silicone-coated Vacutainer tubes (red-topped) and in similar tubes containing
      serum separator gel (SSTs), as well as a postprandial specimen in a red-topped
      tube. The specimens collected in SSTs were left to stand overnight, with the gel
      in contact with the sample. In the second study, the blood of 12 industrial
      incinerator workers was collected in red-topped tubes and in SSTs. Blood in SSTs
      was left in contact with the gel for 5 days. Serum organochlorine residue levels
      ([1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] (DDE)) and polychlorinated
      biphenyls) in samples collected in red-topped tubes were highly correlated with
      levels measured in samples collected in SSTs (all Pearson r values were > or =
      0.79). Postprandial and fasting organochlorine levels were also highly correlated
      (Pearson r values > or = 0.89). Our results indicate that timing of the
      collection of blood in relation to meals and use of SSTs to collect blood
      specimens did not greatly affect the relative classification of subjects with
      respect to serum level of DDE or polychlorinated biphenyls. The longer the
      specimen was in contact with the SST gel, however, the lower the level of
      organochlorine that was detected and, at least for DDE, the greater the
      misclassification caused.

PMID- 8877069
TI  - Correspondence re: letter to the editor by B. K. Tang and W. Kalow on CYP1A2
      phenotyping using caffeine. Cancer Epidemiol. Biomarkers & Prev., 5: 231, 1996.

PMID- 8877071
TI  - Does magnesium supplementation have any role in acute myocardial infarction? No.

PMID- 8877070
TI  - Magnesium in acute myocardial infarction: scientific, statistical, and economic
      rationale for its use.

PMID- 8877072
TI  - Does magnesium supplementation have any role in acute myocardial infarction? Yes.

PMID- 8877073
TI  - Renin inhibitors: cardiovascular drugs of the future?
AB  - This review explores whether the therapeutic attractiveness of renin inhibitors
      compared with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
      receptor antagonists, is sufficient to warrant continued interest in their
      development for the treatment of cardiovascular disease. Clinical and
      experimental data available to date indicate that patients with hypertension and
      congestive heart failure will benefit from renin inhibition. However, clinical
      experience is very limited, and extra benefits of renin inhibitors compared with
      the other blockers of the renin-angiotensin system (RAS) have yet to be
      demonstrated. Some experimental data in animals and humans point to a greater
      effect of acute renin inhibition on renal blood flow than other modes of
      interference with the RAS. Again, the clinical benefits of such an effect, and
      particularly after long-term treatment, in hypertension and renal disease need to
      be determined. In today's cost-conscious health setting, only new drugs that
      bring additional clinical benefits have a good chance of being commercially
      viable. It remains to be seen whether renin inhibitors will fulfill these
      criteria.

PMID- 8877074
TI  - An inpatient trial of the safety and efficacy of losartan compared with placebo
      and enalapril in patients with essential hypertension.
AB  - The antihypertensive activity and safety of losartan, a specific and selective
      antagonist of angiotensin II (subtype 1) receptors, was evaluated in 100
      inpatients with mild to moderate essential hypertension. After a 2-week, single
      blind, out patient placebo lead-in period, the last 2 days of which included
      inpatient monitoring of baseline blood pressure, the patients were assigned
      randomly to receive once-daily doses of either placebo; 50, 100, or 150 mg
      losartan; or 10 mg enalapril. Patients were treated double blind for 5 days,
      followed by a day for the study of drug withdrawal. Beginning with the first
      dose, the three doses of losartan and enalapril significantly decreased peak and
      trough systolic and diastolic blood pressures compared with placebo (p < or =
      0.05). The area under the blood pressure curve was analyzed as an assessment of
      total blood pressure change throughout the day. On day 1, total blood pressure
      reduction with losartan (50-150 mg) was slightly less than with enalapril. By day
      5 of double-blind treatment, the reduction in blood pressure in these groups was
      similar, suggesting that losartan has a slower onset of action than enalapril. No
      rebound hypertension was observed after study-drug discontinuation. Losartan was
      well tolerated in this trial, with an adverse event profile similar to placebo
      and enalapril.

PMID- 8877075
TI  - Left ventricular diastolic function during adrenergic stress in essential
      hypertension: acute and chronic effects of ACE inhibition.
AB  - We studied the changes in left ventricular (LV) diastolic function induced by
      angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic
      stimulation and their relation to blood pressure (BP) variations to determine
      whether reductions in the renin-angiotensin system may improve diastolic function
      irrespective of BP reduction. Echocardiographic indices of systolic and diastolic
      function, plasma catecholamines as estimated by high-pressure liquid
      chromatography, and BP variations (Dynamap) were determined at rest and during
      the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition
      (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential
      hypertension. Blood Pressure was significantly reduced after both 6 hours and 20
      days of therapy. The cold pressor test induced similar increases in BP in both
      basal conditions and after acute and chronic treatment. Catecholamine levels were
      unchanged by the therapy. Systolic function, evaluated by fractional shortening,
      ejection fraction, and systolic dV/dt, was normal and unchanged during CPT and
      after treatment. Diastolic function, assessed by volume curve analysis, showed a
      reduced percentage contribution of rapid filling to total diastolic filling, an
      increase in the contribution of the atrial systole, and an increase in the
      isovolumetric relaxation time. During CPT these parameters deteriorated further
      in response to increased afterload. Lisinopril therapy induced significant
      increases in end-diastolic volume (p < 0.005) with a progressive increase in the
      rapid filling dV/dt (p < 0.005 at rest; p < 0.001 during CPT) and a reduction in
      isovolumetric relaxation (p < 0.0001 at rest and p < 0.01 during CPT). The
      correlation between systolic BP (afterload) and the rapid filling dV/dt, both at
      rest and during CPT, was modified by treatment with the ACE inhibitor, with
      significantly higher rapid filling dV/dt values, and with the pressure loads
      equal (reduction of the slope and rightward shift of the correlation line). The
      improvement in diastolic function achieved by ACE inhibition at rest and during
      CPT appears unrelated to plasma catecholamines and only partly ascribable to the
      reduced pressure load. The tissue angiotensin II reduction might by itself
      improve the myocardial response to the pressure load and adrenergic stimulation.

PMID- 8877077
TI  - Protection from preconditioning can be reinstated at various reperfusion
      intervals.
AB  - The aim of this study was to evaluate the way in which short-term protection
      declines and is eventually lost in preconditioning and to determine the efficacy
      of a second preconditioning at various reperfusion intervals. Male rabbits were
      divided into six groups. Forty-five minutes (sustained) ischemia followed by 120
      minutes reperfusion was applied 60, 65, 70, 75, and 80 minutes after a 5 minute
      preconditioning (groups A, B, C, D, and E) and in a control group (F) after no
      preconditioning. The infarct to risk ratio (I/R) was 38.3 +/- 3.5% in group A,
      46.0 +/- 7.8% in B, 61.6 +/- 9.7% in C, 68.1 +/- 4.2% in D, 64.5 +/- 7.8% in E,
      and 61.0 +/- 7.7% in F. Group A had a smaller I/R compared with groups C, D, E,
      and F (p < 0.05). In another series, groups G, H, and I were exposed to two 5
      minute preconditioning stimuli, separated, respectively, by 45, 60, and 75
      minutes of reperfusion; 10 minutes after the last preconditioning, the animals
      were exposed to 45-minutes ischemia and 120 minutes reperfusion. Groups A and D
      (with the smaller and higher I/R ratio) were also incorporated into this protocol
      in order to compare the effect of the additional preconditioning with the single
      one. The I/R ratio was 25.4 +/- 8.5% in group G, 22.8 +/- 7.0% in group H, and
      14.7 +/- 4.0% in group I (p = NS). Group D showed a higher I/R compared with
      groups G, A, and H (p < 0.01), and group I had a smaller I/R compared with groups
      A (p < 0.01) and D (p < 0.001). Cardioprotection after a first preconditioning
      declines gradually and is eventually lost. An additional preconditioning is
      always effective, and the longer the interval from the first preconditioning, the
      more potent is the effect.

PMID- 8877076
TI  - EUK-8 a synthetic catalytic scavenger of reactive oxygen species protects
      isolated iron-overloaded rat heart from functional and structural damage induced
      by ischemia/reperfusion.
AB  - The effects of EUK-8, a synthetic, catalytic scavenger of reactive oxygen
      species, on isolated iron-overloaded rat hearts submitted to ischemia-reperfusion
      were studied. In the absence of EUK-8, functional parameters (systolic and
      diastolic pressures, oxygen consumption as estimated by the product heart rate
      times left ventricular diastolic pressure) were severely impaired 1 minute and 15
      minutes after reperfusion following a 15 minute ischemic episode.
      Dimethylthiourea (10 mM), a hydroxyl radical scavenger, had a minimally
      protective effect. In contrast, EUK-8 at a concentration of 50 microM in the
      perfusion medium maintained these parameters at close to their preischemia
      values. Electron microscopic analysis of heart tissues after 15 minutes ischemia
      followed by 15 minutes reperfusion showed extensive damage to mitochondria and
      sarcomeres in untreated hearts, while the extent of damage was significantly
      lower in EUK-8-treated hearts. The functional and structural protection afforded
      by EUK-8 were significantly better than those induced by dimethylthiourea. These
      data suggest that EUK-8 may be therapeutically useful in preventing heart damage
      induced by ischemia-reperfusion, for example, during thrombolytic treatment of
      myocardial infarction.

PMID- 8877078
TI  - Attenuation of regional myocardial stunning by felodipine.

PMID- 8877079
TI  - Reversal of Borrelia burgdorferi associated dilated cardiomyopathy by antibiotic
      treatment?
AB  - It is suggested that Borrelia burgdorferi infection could be associated with
      dilated cardiomyopathy (IDC). Stanek et al. were able to cultivate Borrelia
      burgdorferi from myocardial biopsy tissue of a patient with longstanding dilated
      cardiomyopathy. Here we present a study in which we examined the effect of
      standard antibiotic treatment on the left ventricular ejection fraction (LVEF) in
      patients with dilated cardiomyopathy associated with Borrelia burgdorferi
      infection. In this study we assessed the serum (IgG, IgM Elisa) and history of 46
      IDC patients with specific regard to Borrelia burgdorferi infection (mean LVEF
      30.4 +/- 1.3%, measured by cardiac catheterization and echocardiography with the
      length-area-volume method). All 46 patients received standard treatment for
      dilated cardiomyopathy: ACE inhibitors, digitalis, and diuretics. Eleven (24%)
      patients showed positive serology and a history of Borrelia burgdorferi
      infection; nine of these also had a typical history of tick bite and erythema
      chronicum migrans (ECM) and/or other organ involvement, and two had no
      recollection of tick bite or ECM but showed other Borrelia burgdorferi-associated
      disorders (neuropathy, oligoarthritis). These 11 patients with Borrelia
      burgdorferi infection received standard antibiotic treatment with intravenous
      ceftriaxone 2 g bid for 14 days. Six (55%) recovered completely and showed a
      normal LVEF after 6 months, three (27%) improved their LVEF, and two (18%) did
      not improve at all. This amounts to nine (82%) patients with recovery/improvement
      in the Borrelia burgdorferi group. The 35 patients who did not show positive
      serology or a history of Borrelia burgdorferi infection did not receive
      antibiotic treatment. In this group without Borrelia burgdorferi infection 12
      (26%), showed recovery/improvement following the standard treatment of dilated
      cardiomyopathy (see earlier). Our results indicate that Borrelia burgdorferi
      infection could play a decisive role in the development of dilated
      cardiomyopathy, especially in a geographical region such as Graz, where Borrelia
      burgdorferi is endemic. While we are aware of the small number of Borrelia
      burgdorferi patients in this study, we nevertheless conclude that in a remarkable
      number of patients with signs of Borrelia burgdorferi infection, dilated
      cardiomyopathy could be reversed and LVEF improved.

PMID- 8877080
TI  - Quality of life on treatment with metoprolol in dilated cardiomyopathy: results
      from the MDC trial. Metoprolol in Dilated Cardiomyopathy trial.
AB  - Quality of life in heart failure patients is receiving increased attention as a
      reflection of a treatment's potential secondary benefit of general well-being and
      daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was
      conducted as a large, multicenter trial to establish the effects of metoprolol on
      mortality and need for heart transplantation in patients with symptomatic
      idiopathic cardiomyopathy. It was found that metoprolol was well tolerated,
      improved symptoms and cardiac function, and prevented clinical deterioration in
      patients with symptomatic idiopathic dilated cardiomyopathy. Quality of life was
      evaluated as a secondary endpoint in 345 out of 383 randomized patients using a
      disease-specific questionnaire, the Quality of Life in Heart Failure
      Questionnaire, depicting physical activity, somatic symptoms, emotions, and life
      satisfaction. In a comparison of patients treated with metoprolol or placebo,
      patients treated with metoprolol noted a significantly more favorable response
      than those treated with placebo in terms of the overall treatment evaluation (p <
      0.05). Additionally, an analysis of the changes from baseline to 18 months, using
      95% confidence intervals, revealed that patients treated with metoprolol showed a
      significant improvement from baseline to 18 months in life satisfaction, physical
      activity, and the total score, while patients treated with placebo did not change
      at all. The improvement in quality of life was supported by the correlations with
      improvement in traditional clinical parameters.

PMID- 8877081
TI  - Effects of hypothyroidism on the vulnerability to ventricular fibrillation in
      dogs: a comparative study with amiodarone.
AB  - It has been shown that thyroid hormone has a significant effect on the heart and
      that suppression of thyroid function may contribute to the antiarrhythmic effect
      of amiodarone. The study was aimed at investigating the effects of
      hypothyroidism, compared with those of amiodarone, on vulnerability to
      ventricular fibrillation in dogs. In this study, 25 adult dogs were randomly
      divided into three groups: a hypothyroid group following total thyroidectomy (n =
      9), an amiodarone group (n = 8, 400 mg per day, 4 weeks), and a control group (n
      = 8). Both amiodarone and control groups were subjected to sham surgery. Five to
      8 weeks after surgery, ventricular fibrillation threshold and other
      electrophysiological parameters were determined. Right ventricular effective
      refractory period, monophasic action potential duration, and ventricular
      fibrillation threshold were significantly increased in both the thyroidectomized
      and amiodarone-treated animals. There was no significant change in monophasic
      action potential duration dispersion. The incidence of ventricular fibrillation
      during ischemia and reperfusion was significantly reduced in both treated groups
      compared with the sham-operated euthyroid controls. These observations suggest
      that hypothyroidism has a significant antifibrillatory effect in dogs.
      Homogeneous prolongation of repolarization and refractoriness may contribute to
      the antifibrillatory action of hypothyroidism.

PMID- 8877083
TI  - Cavitation at radiolucent areas on proximal surfaces of posterior teeth.
AB  - To investigate the factors that influence the probability of clinical cavitation
      at radiolucent areas of proximal surfaces of posterior teeth, 108 molars and
      premolars with varying depths of proximal radiolucency were examined clinically,
      after cavity preparation on the carious contiguous tooth surfaces. The data
      obtained were subjected to logistic regression analysis with cavitation as the
      dependent variable, while age, tooth type and past caries experience (DMFT and
      DFS) were independent variables. When proximal radiolucency was confined to the
      outer half of enamel, there was no cavitation, but when it extended to the
      amelodentinal junction and the outer and inner half of dentine, there was
      cavitation in 19.3, 79.1 and 100% of cases, respectively. Moreover, there was a
      statistically significant relationship between the probability of cavitation,
      depth of radiolucency and age, suggesting that these should be among the main
      factors considered when restorative management of a radiolucent proximal surface
      of a posterior tooth is contemplated.

PMID- 8877082
TI  - Effect of dietary supplementation with fish oil on cyclosporine A-induced
      vascular toxicity.
AB  - We wished to determine whether dietary supplementation with fish oil prevents the
      vascular toxicity of cyclosporine (Cx). In a first set of experiments, we
      assessed the endothelial function of aortas isolated from rats supplemented for 6
      weeks with fish oil (FO), administered by gavage, and providing 150 mg/kg/day of
      eicosapentaenoic acid and 100 mg/kg/day of docosahexaenoic acid. FO treatment
      altered neither acetylcholine- and histamine-induced relaxations, nor serotonin
      induced contractions (NS vs. control group). Thereafter, three groups of rats
      were treated in parallel. Group 1 received FO supplementation (by gavage) for 6
      weeks, and Cx (10 mg/kg/day po) was added during the last 2 weeks, group 2
      received Cx only (10 mg/kg/day po) for 2 weeks, and group 3 served as a control.
      Both acetylcholine-and histamine-induced relaxations were reduced in group 2
      compared with the control group, as indicated by the area under the curve (AUC),
      which was significantly higher: 296 +/- 17 vs. 138 +/- 32, and 392 +/- 38 vs. 318
      +/- 25 for acetylcholine and histamine, respectively. In group 1, AUC for
      acetylcholine remained significantly different from the control (241 +/- 31 vs.
      138 +/- 32), whereas AUC for histamine was 367 +/- 28 (NS vs. control). The
      serotonin-induced contractions were also enhanced in group 2 compared with those
      of the control group, and this alteration was not attenuated in group 1. After
      mechanical removal of the endothelium, the increased responsiveness to serotonin
      persisted in groups 1 and 2, suggesting this functional alteration to be located
      in the smooth muscle cells. Thus, in the rat the attenuation of Cx-induced
      vascular toxicity by fish oil supplementation is only partial, that is, it
      involves a slight improvement in endothelial function, but with persistence of
      functional changes in smooth muscle.

PMID- 8877084
TI  - Measurement of enamel demineralization using microradiography and confocal
      microscopy. A correlation study.
AB  - Substantial amounts of tooth minerals are lost during dental caries formation.
      Transversal microradiography, a well-accepted method used to quantify mineral
      loss, is a time-consuming technique which requires a thin enamel section (100
      microns) and involves the use of x-rays. In an attempt to solve these
      difficulties, a procedure has been developed in which a human tooth specimen with
      demineralized enamel is cut in half (HT), stained with a fluorescent dye
      (rhodamine B) and analyzed using a laser scanning confocal microscope. A series
      of three studies was conducted to correlate measurements of enamel
      demineralization obtained from enamel thin (100 microns) sections (TS) using
      transversal microradiography with three parameters (area of the lesion; total and
      average dye fluorescence intensities) measured on the same TS or on a thicker
      section (HT) of the same specimen by laser scanning confocal microscopy. Results
      showed that a 0.1 mM rhodamine B solution provided the most adequate imaging
      conditions for confocal microscopy. Pearson's correlation coefficients,
      calculated between microradiography and confocal microscopy data obtained using a
      0.1 mM rhodamine B solution, were: delta Z vs. HT lesion area = 0.95; delta Z vs.
      HT total fluorescence = 0.80; delta Z vs. HT average fluorescence = 0.74; delta Z
      vs. TS lesion area = 0.95; delta Z vs. TS total fluorescence = 0.74; delta Z vs.
      TS average fluorescence = 0.55. All these correlations coefficients were
      statistically significant (p < 0.01). It is concluded that in enamel
      demineralization studies statistically significant correlations exist between
      parameters measured using transversal microradiography and parameters quantified
      using confocal microscopy.

PMID- 8877085
TI  - A method to monitor dental demineralisation in vitro.
AB  - This paper presents an in vitro method for monitoring the progression of dental
      hard tissue demineralisation using consecutive, standardised radiographs.
      Reliability and factors affecting the reproducibility of this method were
      established by replicate measurements and comparison to histological evaluation.
      Whereas assessment of the extent of the lesions by measuring linear distances was
      highly reproducible, reproducibility of measurements of the central depth of a
      lesion is affected by the superficial extension and the surrounding hard tissue.
      Radiographic imaging underestimates the extent of demineralisation as compared to
      histological analysis.

PMID- 8877086
TI  - Changes in caries prevalence in children and young adults of Dutch and Turkish or
      Moroccan origin in The Netherlands between 1987 and 1993.
AB  - In 1987, an epidemiological study was started with the aim to evaluate the
      development of dental health in young people insured by "Health Insurance Funds'.
      In The Netherlands, insurance by such funds is compulsory for individuals earning
      less than some income criterion (in 1995 59,000 Dutch florins) and their
      families, together approximately 60% of the Dutch population. Dental health care
      is included in the insurance. Caries data were obtained in subjects aged 5-23
      years in 1987, 1990 and 1993. Mean DMFS scores of groups aged 11, 17 or 23 years
      in 1993 were about 40% lower than in 1987. No significant differences in mean
      number of dmfs of 5-year-olds in 1987 and 1993 could be observed. A breakdown by
      country of birth of the mother showed that the difference between indigenous
      Dutch juveniles and juveniles of Turkish or Moroccan origin depended on year of
      birth. Caries prevalence of Turkish or Moroccan children born in 1982 or later
      was higher than that of Dutch children of equal age; no significant difference in
      DMFS could be demonstrated between ethnic categories in juveniles born in 1976.
      In cohorts born before 1976, DMFS scores of Turkish/Moroccan juveniles were much
      lower than those of Dutch juveniles. It is suggested that these opposite trends
      were caused by the fact that subjects in the youngest cohorts had been born in
      The Netherlands, while the oldest cohorts spent the first years of their life in
      those parts of Turkey or Morocco where caries prevalence of children is low.
      Between 1987 and 1993 caries prevalence in 5-year-old children of Turkish or
      Moroccan origin decreased significantly.

PMID- 8877087
TI  - Comparison of the plaque pH response to an acidogenic challenge in children and
      adults.
AB  - This study investigated differences in the response of dental plaque pH after a
      carbohydrate challenge in children and adults. A 10% (w/v) sucrose solution and a
      blackcurrant drink containing 7% carbohydrate (w/v) were assessed for their
      ability to depress plaque pH in vivo in 10 adults aged between 16 and 35 years
      and 10 children aged between 4 and 6 years using the plaque harvesting technique.
      The results showed that the plaque pH response was significantly less acidic in
      children. The maximum pH drop and area under the curve below pH 6.0 (+/- SD) with
      sucrose was: children 1.10 +/- 0.35 and 0.98 +/- 0.31 and adults 1.43 +/- 0.24
      and 6.25 +/- 2.10, respectively. The plaque pH also stayed below pH 6.0 for a
      longer period in adults. Similar results were obtained for the blackcurrant drink
      where the responses were lower than with 10% sucrose. When the acidogenic
      potential index (API) for the blackcurrant drink was calculated based on the data
      from the adult volunteers, it was twice as high as compared with the API score
      calculated from the data from children. It was concluded that the as plaque pH
      responses were significantly less acidic in children as compared with adults,
      acidogenicity studies of children's foods and drinks should be carried out in
      children rather than adults.

PMID- 8877088
TI  - Caries incidence in relation to salivary mutans streptococci and fluoride varnish
      applications in preschool children from low- and optimal-fluoride areas.
AB  - Caries incidence during a 2-year period was studied in 4- to 5-year-old children
      from three areas with contrasting levels of natural fluoride (F) in the drinking
      water and different regimens of topical fluoride varnish applications; group A (n
      = 448) was from an area with a low level of F (0.1 ppm) and semi-annual
      applications of fluoride varnish; group B (n = 374) was from a low F area (0.1
      ppm) and no fluoride varnish treatments; group C (n = 206) was from an area with
      optimal F (1.2 ppm) and fluoride varnish treatments. All children were clinically
      assessed at baseline and after 2 years according to WHO criteria. The number of
      salivary mutans streptococci was estimated and scored at baseline and after 2
      years with the Strip mutans method. The varnish containing 0.1% F was applied
      every 6 months on all accessible tooth surfaces after cleaning with a pumice
      paste. Basic preventive care was given to all children and restorative treatment
      on individual indications. Higher levels (p < 0.05) of salivary mutans
      streptococci were found in the low-fluoride areas compared to the optimal
      fluoride area at baseline and after 2 years. The caries incidence (mean dft +/-
      SD) in the different groups was A: 0.65 +/- 1.40; B: 1.09 +/- 1.85; C: 0.53 +/-
      1.09. The difference between group B and groups A and C was statistically
      significant (p < 0.05). A positive relationship (p < 0.05-0.001) between salivary
      mutans streptococci scores at baseline and caries incidence was found in all
      three groups. This study confirms the close association between salivary mutans
      streptococci and caries incidence in preschool children and suggests a caries
      reducing effect of topical applications of the fluoride silane varnish.

PMID- 8877089
TI  - Characterization of glucosyltransferase of human saliva adsorbed onto
      hydroxyapatite surfaces.
AB  - Activities of glucosyltransferases (Gtf)-B, -C and -D adsorbed on the surface of
      saliva-coated hydroxyapatite were compared with those of Gtfs of donor whole
      saliva. Antiserum raised against a mixture of the three Gtfs reduced the activity
      of GtfB only, and had no effect on donor Gtf activities. GtfB, and not the Gtfs
      of the donors, was stimulated in the presence of starch hydrosylates. GtfD and
      GtfC activities were enhanced on the surfaces, as were the Gtf activities of
      donor salivas. The activities of GtfD and GtfB, but not GtfC, were stimulated by
      dextran. The donor Gtf activities were unaffected by dextran. Therefore, Gtf
      activity in pellicles has properties similar to those of GtfC.

PMID- 8877090
TI  - Salivary factors in vomiting bulimics with and without pathological tooth wear.
AB  - The increased occurrence of dental erosion from self-induced vomiting in bulimia
      nervosa is not linearly associated with the frequency or the duration of
      vomiting. Possible changes in the buffering and lubricating role of saliva in
      bulimia nervosa and their relationship to erosion have not been previously
      investigated. Chewing-gum-stimulated salivary flow rate, pH, bicarbonate
      concentration and viscosity were compared between two groups of vomiting bulimics
      and with 10 healthy controls. One bulimic group (n = 9) had pathological tooth
      wear present according to the criteria of the Tooth Wear Index and the other
      bulimic group (n = 10) did not. The influence of salivary pellicle on enamel acid
      dissolution by perchloric acid was also assessed by an enamel biopsy method.
      Bicarbonate was measured in a Natelson microgasometer. Both the bulimic groups
      had mean initial 3-min flow rates and overall 9-min flow rates significantly
      lower (p < 0.01) than the healthy subjects. The mean pH values were not
      significantly different between the two bulimic groups or the control group.
      However, the mean bicarbonate concentration in both bulimic groups was
      significantly less (p < 0.01) than in the control group. The mean salivary
      viscosity of 7.4 centipoise (cP), measured by a DV1 Brookfield viscometer, was
      significantly greater (p < 0.05) in the pathological tooth-wear-present group
      than in the tooth-wear-absent group (4.5 cP) and the control group (4.1 cP).
      Slightly more calcium was released from the pellicle-free surface in both groups
      but this was not statistically significant, whilst the dissolved calcium in
      enamel biopsies was significantly lower (p < 0.05) in the tooth-wear-present
      group.

PMID- 8877091
TI  - Effect of copper co-crystallized with sugar on caries development in desalivated
      rats.
AB  - The purpose of the present study was to explore the effects of varying levels of
      copper incorporated in sucrose by co-crystallization on caries development in the
      desalivated rat model and to examine the retention of copper in the oral cavity
      and its influence on protein and carbohydrate composition of plaque. Forty-eight
      Sprague-Dawley rats were infected by Streptococcus sobrinus 6715 and desalivated
      when aged 26 days. Four groups were placed in a Konig-Hofer programmed feeder and
      received 17 meals daily at hourly intervals, and essential nutrition (NCP No. 2)
      by gavage twice daily. The control group (1) received meals of plain sucrose, and
      groups 2, 3, and 4 received sucrose co-crystallized with 300 ppm Cu2+(2), 150
      Cu2+(3), and 75 Cu2+(4). After 3 weeks, the animals were killed, and blood was
      collected for determination of copper. The lower jaw was removed and sonicated in
      0.9% saline solution. Microbial assessment and copper, protein and carbohydrate
      assays were performed for each animal. Smooth-surface and [sulcal] caries scores
      were: (1) 92.0[41.4]; (2) 6.1[34.2]; (3) 16.7[32.0]; (4) 24.0[36.0]. Copper in
      sucrose drastically affected the population of S. sobrinus when compared with the
      control. Also, Cu2+ sucrose groups had significantly more copper per unit of
      protein and carbohydrate in jaw suspension than the control group. Concentration
      of copper in the blood was apparently unaffected by any dietary regimen. It is
      concluded that Cu2+ in a range of concentrations (75-300 ppm Cu2+) when delivered
      co-crystallized with sucrose is an effective cariostatic agent. The co
      crystallization of a cariostatic agent with sucrose may be an effective method to
      decrease the cariogenic potential of sucrose.

PMID- 8877092
TI  - In vitro study of enamel erosion caused by soft drinks and lemon juice in
      deciduous teeth analysed by stereomicroscopy and scanning electron microscopy.
AB  - The erosion caused in vitro by cola-type and guarana-type beverages (the latter
      is a soft drink sold in Brazil), and a canned lemon juice on the enamel of human
      deciduous teeth was analyzed. Morphological analysis of affected enamel was done
      using stereomicroscopy and scanning electron microscopy (SEM). The harmful effect
      of all test products on deciduous enamel was clearly demonstrated.
      Stereomicroscopy showed loss of gloss and an alteration in normal color of
      enamel, with irregular loss of dental tissue in variable degrees. Such a loss
      became more serious as the time of incubation increased. Different degrees of
      solubilization of enamel prisms were demonstrated by SEM, affecting initially the
      sheaths and the heads of prisms and later their tails. Areas of erosion increased
      in proportion to the time of incubation. All the products showed a great erosive
      potential on human deciduous dental enamel.

PMID- 8877093
TI  - Differentiation induced by the c-Mpl cytokine receptor is blocked by mutant Shc
      adaptor protein.
AB  - c-Mpl, a member of the cytokine receptor superfamily, induces both proliferative
      and differentiation responses when stimulated with its ligand thrombopoietin
      (TPO). To examine signal transduction pathways associated with differentiation
      versus proliferation, 32D clone 3 cells, a murine interleukin 3-(IL-3)-dependent
      cell line capable of granulocytic differentiation, were engineered to express
      human c-Mpl (designated 32DM.2). Human TPO-containing medium was produced by
      transient transfection of 293 cells. Treatment of 32DM.2 cells with human TPO
      induced cellular aggregates within 12 h of exposure to ligand. 32DM.2 cells
      maintained in the presence of TPO did not change in cell number over a 72-h
      period and acquired characteristics of granulocytic differentiation as evidenced
      by metamyelocytic cellular morphology. The differentiation effect of TPO was
      observed in the absence and presence of the mitogen IL-3. Evaluation of protein
      tyrosine phosphorylation following exposure to ligand revealed that TPO
      stimulation induced an elevated level of tyrosine phosphorylation of the adaptor
      protein Shc when compared with IL-3. However, treatment of 32DM.2 cells with TPO
      did not result in the phosphorylation of mitogen-activated protein kinase (MAPK).
      To evaluate the potential role of Shc in c-Mpl differentiation, we transfected
      32DM.2 cells with a mutant Shc gene that lacked the region coding for the
      phosphotyrosine interaction domain (delta PI-Shc). Expression of the delta PI-Shc
      protein in 32DM.2 cells blocked the TPO differentiation response with no effect
      on IL-3-stimulated proliferation. These studies demonstrate that c-Mpl-induced
      differentiation results from the activation of signal transduction pathways that
      are dominant to the IL-3 proliferative response and independent of the Ras/MAPK
      signal transduction pathway. The ability of the delta PI-Shc protein to block TPO
      induced differentiation implicates Shc as a mediator of signal transduction
      pathways leading to differentiation, which is distinct from its role as a
      mediator in activating the Ras/MAPK pathway.

PMID- 8877094
TI  - Tec protein tyrosine kinase is involved in the signaling mechanism of granulocyte
      colony-stimulating factor receptor.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a critical cytokine to promote
      the growth, differentiation, and functional activation of myeloid cells. Despite
      its important roles, little is still understood how one cytokine can trigger such
      pleiotropic effects. By using mouse cell lines which can grow or differentiate in
      response to G-CSF, we investigated whether Tec protein tyrosine kinase is
      involved in either of the signaling pathways. Interestingly, Tec is shown to be
      tyrosine phosphorylated and activated by the G-CSF stimulation in both cell
      growth and differentiation mechanisms. Vav is also shown to be associated with
      Tec and tyrosine phosphorylated in response to G-CSF. Tec is a good candidate for
      protein-tyrosine kinases involved in both growth and differentiation mechanisms
      of myeloid cells.

PMID- 8877095
TI  - Isoform-specific functions of c-abl: type I is necessary for differentiation, and
      type IV is inhibitory to apoptosis.
AB  - The c-abl proto-oncogene is expressed ubiquitously during development. There are
      two predominant isoforms, type I and type IV. Their biological functions in cell
      growth and development are unknown. To examine their respective biological roles,
      we transduced 70Z/3 lymphoid cells with antisense sequences specific to each
      respective isotype. When the cells were incubated with antisense oligonucleotides
      against type IV c-abl but not against type I c-abl, induction of apoptosis was
      observed, as measured by either DNA fragmentation, cell proliferation, or colony
      formation. Immunoprecipitation showed that antisense-treated cells had reduced
      amounts of c-abl as compared to the untreated cells. When stimulated with
      lipopolysaccharide (LPS), 70Z/3 cells underwent proliferation and
      differentiation. When antisense oligonucleotides against type IV were added to
      the cell cultures, with LPS stimulation, induction of apoptosis continued to
      occur. When antisense oligonucleotides against type I were added in the cultures,
      in the presence of LPS, cell differentiation was inhibited, but cell
      proliferation continued to occur. This inhibition of differentiation was evident
      by a lack of immunoglobulin light chain production by cells that otherwise would
      produce immunoglobulin when they are stimulated with LPS. These data therefore
      show that type I c-abl allows cell differentiation to occur, whereas type IV c
      abl suppresses apoptosis.

PMID- 8877096
TI  - Cell-substratum interactions mediate oncogene-induced phenotype of lung cancer
      cells.
AB  - In vivo and in vitro studies have linked small cell lung cancer (SCLC) and non
      small cell lung cancer (NSCLC) cells along a differentiation continuum. The
      transition of a SCLC toward a NSCLC phenotype is modeled in culture by the
      simultaneous overexpression of myc and ras genes in cultured SCLC cells. A major
      phenotypic distinction between SCLC and NSCLC in culture is that SCLC cells
      usually grow in floating aggregates, whereas NSCLC cells and myc- plus ras
      expressing SCLC cells grow as adherent spreading monolayers like other epithelial
      cells. The present studies examine how myc, ras, cell aggregation, and attachment
      to laminin may interact to modulate transitions between the SCLC and NSCLC
      phenotypes. We find that myc-expressing SCLC cells, which normally grow as
      anchorage-independent cells in plastic flasks, will adhere to laminin and exhibit
      an epithelial morphology. In this setting, the cells express both NSCLC and SCLC
      markers, thus resembling a tumor type previously termed NSCLC with neuroendocrine
      features. Anchorage-dependent SCLC cells simultaneously expressing the myc family
      and an exogenous ras oncogene move further toward the NSCLC phenotype than the
      above myc-expressing cells. However, forced suspension of such cells restores the
      expression of neuroendocrine SCLC features. These studies indicate that cell
      environment, as much as gene expression events, profoundly affects aspects of the
      SCLC cell phenotype.

PMID- 8877097
TI  - Effect of decreased fte-1 gene expression on protein synthesis, cell growth, and
      transformation.
AB  - The fte-1 gene, previously cloned in our laboratory as a putative v-fos
      transformation effector gene (C.J. Kho and H. Zarbl, Proc. Natl. Acad. Sci. USA,
      89: 2200-2204, 1992), has been shown to encode ribosomal protein S3a. Comparison
      of fte-1 expression in a variety of normal and transformed cells indicated that
      elevated expression of fte-1 mRNA was frequently associated with transformation
      of rodent and human cells. In an effort to understand how monoallelic disruption
      of fte-1 is able to block v-fos-induced cell transformation, we examined the
      pattern of fte-1 expression during cell cycle progression and determined its
      effects on protein synthesis and cell growth. In synchronously cultured human
      fibroblasts, fte-1 mRNA was found to accumulate in cells undergoing DNA
      synthesis, suggesting that its expression is correlated with S-phase progression.
      fte-1 does not function as a dominant oncogene because ectopic overexpression of
      fte-1 in normal Rat-1 fibroblasts failed to induce cell transformation. However,
      the expression of antisense fte-1 resulted in growth inhibition. Monoallelic
      disruption of the fte-1 gene in v-fos-transformed Rat-1 fibroblasts resulted not
      only in loss of the transformed phenotype but also in a decreased rate of protein
      synthesis due to decreased polysome formation. Taken together, these results
      indicate that the accumulation of ribosomal subunits and the rate of protein
      synthesis are important modulators of neoplastic transformation and cell growth.

PMID- 8877098
TI  - Modification of growth and tumorigenicity in epidermal cell lines by DNA-mediated
      gene transfer of M(r) 27,000 heat shock protein (hsp27).
AB  - In the present communication, the role of the M(r) 27,000 human small heat shock
      protein (hsp27) in tumorigenicity was examined. Stable transfectants of a
      melanoma cell line (A375) and an epidermal squamous carcinoma cell line (A431),
      isolated by cotransfection of a hsp27 expression vector (pSG-2711) and a neomycin
      resistant plasmid, were obtained. Clones expressing high levels of hsp27 were
      analyzed using immunohistochemistry and immunoblotting. Cells transfected with
      only the plasmid for neomycin were used as control cells. Growth analysis of
      transfectants in A375 and A431 tumor cells showed in vitro a lower proliferation
      rate than control clones derived from both lines. To investigate the correlation
      of hsp27 expression and tumorigenicity, transfectants of each cell type and
      control cells were injected into nude mice. A delay in tumor development was
      detected in animals inoculated with cells overexpressing hsp27. However, after
      this initial delay, tumors appeared in some of these animals and no difference
      could be observed in their growth dynamics compared to control tumors. When
      tumors transfected with the hsp27 construct were analyzed using
      immunohistochemistry and PCR, no evidence for hsp27 expression was obtained which
      implicates instability of the transduced foreign DNA when maintained under
      nonselective conditions. The present study shows that genetic manipulation of
      tumor cells may provide valuable information on the role of hsp27 in tumor
      growth.

PMID- 8877099
TI  - Inhibition of cell growth and sensitization to oxidative damage by overexpression
      of manganese superoxide dismutase in rat glioma cells.
AB  - The effects of overexpression of human manganese superoxide dismutase (MnSOD) on
      cell proliferation and response to oxidative stress in rat glioma cells were
      studied. MnSOD-overexpressing cells had a 2- to 14-fold increase in MnSOD
      activity, but did not have consistent changes in the activities of CuZnSOD,
      catalase, or glutathione peroxidase. Cells with more than a 5-fold increase in
      MnSOD activity became more sensitive to radiation, 1,3-bis(2-chloroethyl)-1
      nitrosourea, and buthionine sulfoximine and had a lower growth rate than parental
      and vector control cells. The sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea
      was partially reduced by pyruvate, a H2O2 scavenger. Our results suggest that
      overexpression of MnSOD can cause an imbalance of antioxidant enzymes, which we
      hypothesize results in an elevation of intracellular H2O2. Overexpression of
      MnSOD can either inhibit cell proliferation or increase cell death by oxidative
      agents, depending on the levels of peroxide-removing enzymes.

PMID- 8877100
TI  - Induction of a less aggressive breast cancer phenotype by protein kinase C-alpha
      and -beta overexpression.
AB  - To address the isoenzyme-specific involvement of protein kinase C (PKC) in breast
      cancer biology, hormone-responsive MCF-7 breast cancer cells were infected with
      either PKC-alpha or -beta 1 cDNAs subcloned in the retroviral expression vector
      pMV7. Several stable clones of PKC-overexpressing cells were generated. Western
      analysis revealed cross-regulation between the alpha and beta isoforms, because
      induction of overexpression of one up-regulated the other. Overexpression of the
      alpha and beta isoenzymes, on the other hand, did not affect the already high
      endogenous expression of the novel delta, epsilon, eta, and zeta isoforms.
      Compared with control clones, PKC-alpha- and -beta-overexpressing MCF-7 cells
      exhibited more drastic morphological changes in response to phorbol 12-myristate
      13-acetate administration characterized by cellular flattening and vacuolization.
      More importantly, induction of PKC-alpha and -beta overexpression induced a less
      aggressive biological behavior, which was characterized by reduced in vitro
      invasiveness and markedly diminished tumor formation and growth in nude mice.
      These in vivo findings can probably best be explained by the dramatic down
      regulation of estrogen receptor levels observed in tumors derived from PKC-alpha
      infected MCF-7 cells. Our data clearly show that it is possible to induce a less
      aggressive breast cancer phenotype by altering PKC isoenzyme expression.

PMID- 8877101
TI  - Okadaic acid induces cellular hypertrophy in AKR-2B fibroblasts: involvement of
      the p70S6 kinase in the onset of protein and rRNA synthesis.
AB  - At low concentrations (50 nM), okadaic acid (OA), an inhibitor of phosphatases 1
      and 2A, inhibits platelet-derived growth factor-induced cell proliferation in
      late G1 (A. Simm et al., Exp. Cell Res., 210: 160-165, 1994). This inhibition is
      caused by the interference of OA in the induction and activation of the cell
      division protein kinases cdk1 and cdk2. OA alone has no effect on cell number,
      but induces a pronounced increase in cell size. The OA-induced hypertrophy can be
      divided into two phases. The first phase is characterized by a swelling of the
      cells. This increase in cellular volume is not accompanied by a change in the
      level of cellular macromolecules, i.e., protein and RNA. Inhibitor studies
      indicated a possible role of the Na+/H+ antiporter and Cl- channels in this
      process. In the second phase, an increase in the cellular protein and RNA content
      was observed along with a minor change in cell volume. To delineate a possible
      signaling pathway, the involvement of numerous protein kinases was analyzed. Low
      concentrations of OA lead to pronounced and sustained activation of the p70S6
      kinase. There was little or no effect on various other kinases that can be
      activated by extracellular signals, e.g., mitogen-activated kinase, ribosomal S6
      kinase, or other S6 peptide kinases. Likewise, at these concentrations, OA did
      not activate the genes for fos, myc, or ornithine decarboxylase. At very low
      concentrations (ED50, 0.5 nM), rapamycin, a specific inhibitor of the activation
      of p70S6 kinase, reversed the activation of the p70S6 kinase and the enhancement
      of RNA synthesis and partially the increase in cell volume and protein synthesis.
      The OA-induced hypertrophy of AKR-2B fibroblasts may serve as a model system for
      investigations aimed at the identification of signaling pathways leading to
      hypertrophy of differentiated nonproliferating cells.

PMID- 8877102
TI  - Cell cycle-dependent regulation of nuclear p53 traffic occurs in one subclass of
      human tumor cells and in untransformed cells.
AB  - We have analyzed the regulation of subcellular compartmentation of mutant and
      wild-type (WT) p53 proteins as a function of the cell cycle using
      immunofluorescence microscopy and referring to different markers of position in
      the cell cycle in different human cells expressing either mutated (KHOS-240, A
      431, and T47-D cells) or WT (WI 38 and MCF-7 cells) p53. The mutant p53 proteins
      present in the KHOS-240, A 431, and T47-D tumor-derived cell lines enter very
      rapidly in the nucleus in early postmitotic cells before the chromosomes have
      fully decondensed; they continue accumulating in this location without any
      obvious cytoplasmic retention throughout the cell cycle until prophase. Such
      behavior is similar to that observed for the WT p53 associating with SV40 large T
      antigen in human WI 38 cells transformed by SV40, but it is in contrast to the
      behavior of the WT p53 protein present in both the untransformed WI 38 and the
      tumor-derived MCF-7 cells. In these latter systems, the highest nuclear
      concentrations of the WT protein are always found in G1 cells that still fail to
      exhibit a high rate of nuclear cyclin A; past the G1-S transition, the nuclear
      level of WT p53 tends to decrease, possibly to the benefit of cytoplasmic
      expression, whereas that of cyclin A concomitantly increases, suggesting that the
      nuclear accumulation of WT p53 becomes restricted during the phase of DNA
      replication. As for Saos-2 cells stably transfected with the temperature
      sensitive p53Ala-143 mutant, they become arrested before the G1-S transition with
      a heavy pool of nuclear p53 at 32.5 degrees C, the temperature at which the
      transcriptional activity of p53Ala-143 is restored. All these data are compatible
      with the presently acknowledged primary role for WT p53, which would be to brake
      transit through the G1-S border possibly by directly transactivating the p21cip1
      protein.

PMID- 8877103
TI  - Localization of sequences that influence basal and cell type-specific activity of
      the murine mdr2 promoter.
AB  - The mdr2 gene is highly expressed in liver and is involved in the translocation
      of phospholipid. To study the regulation of mdr2 expression, the promoter of the
      mdr2 gene has been isolated from a murine vinblastine-resistant cell line, J7.V2
      1, and characterized. The 5' flanking region of this gene is GC-rich, has
      multiple transcription initiation sites as mapped by primer extension, and does
      not contain either TATA or CCAAT boxes. To test promoter activity, a 1.9-kb (
      1867 to +37) DNA fragment was cloned in front of the luciferase reporter gene and
      transient transfection assays were done in a variety of cell lines. The promoter
      luciferase construct displayed a 20- to 120-fold increase in activity compared to
      the promoterless vector. 5' and 3' deletion analysis using transient
      transfections revealed two major regulatory regions in the promoter, one located
      upstream and one situated downstream of the transcription start sites. The
      upstream region may be involved in basal expression and the downstream sequence
      may be involved in cell type-specific expression of the mdr2 gene. Gel mobility
      shift and DNA footprinting assays have identified a 29-bp sequence (-78 to -50)
      to which nuclear protein binds. Methylation interference analysis using this
      fragment has further determined that CTGGCAGCTCGCCC, within the 29-mer, contains
      the core sequence with which nuclear protein directly interacts. Mutation of the
      core sequence reduced basal promoter activity, indicating that it is involved in
      the basal expression of the mdr2 gene. Mutagenesis studies also suggested that
      the upstream and downstream sequences act independently in regulation of cell
      type-specific mdr2 expression.

PMID- 8877104
TI  - Vitamin D3- and retinoic acid-induced monocytic differentiation: interactions
      between the endogenous vitamin D3 receptor, retinoic acid receptors, and retinoid
      X receptors in U-937 cells.
AB  - Retinoic acid (RA) and 1,25 alpha-dihydroxycholecalciferol (VitD3) are potent
      regulators of hematopoletic differentiation. Yet, little is known as to how the
      RA and VitD3 receptor network operates in hematopoietic cells, and whether
      receptor interactions can explain the interplay between the RA- and VitD3
      signaling pathways during differentiation. Therefore, we analyzed the expression,
      DNA binding, and transcriptional activity of the endogenous RA and VitD3
      receptors [retinoic acid receptors (RARs), retinoid X receptors (RXRs), and VitD3
      receptor (VDR)] in the U-937 cell line, in which RA and VitD3 induce distinct
      monocytic differentiation pathways. VitD3 induction resulted in the formation of
      VDR/RXR DNA-binding complexes on both VitD3 response elements and RA response
      elements (RAREs). However, transcriptional activation was only observed from a
      VitD3 response element-driven reporter construct. Several DNA-binding complexes
      were detected on RAREs in undifferentiated cells. Stimulation by RA resulted in
      increased RAR beta/RXR DNA binding, activated RARE-dependent transcription, and
      increased expression of RAR-beta. Concomitant stimulation by VitD3 inhibited the
      RA-stimulated formation of RAR beta/RXR heterodimers, favoring VDR/RXR binding to
      the RARE. Also, VitD3 inhibited the expression of CD23 and CD49f, characteristic
      markers of retinoid-induced U-937 cell differentiation. In contrast, neither the
      RA-stimulated, RARE-mediated transcription nor the induced RAR-beta expression
      was suppressed by VitD3, suggesting that VitD3 selectively inhibited the retinoid
      induced differentiation program but not the RARE-mediated signal. These results
      demonstrate a complex role for VitD3 in modifying the retinoid differentiation
      pathway and may have implications for differentiation-inducing therapy of
      hematopoietic tumors.

PMID- 8877105
TI  - p21ras induced differentiation-related gene expression in fetal brown adipocyte
      primary cells and cell lines.
AB  - Transfection of primary rat fetal brown adipocytes with constructs of SV40 large
      T antigen, alone and together with lys12-mutated H-ras gene, gave permanent cell
      lines showing an immortalized or transformed phenotype, respectively, all of them
      selected by the expression of the uncoupling protein (UCP), a tissue-specific
      marker. Primary brown adipocytes and immortalized cell lines respond to insulin
      like growth factor I (IGF-I) by increasing their lipid content and the mRNA
      expression of both the adipogenic marker fatty acid synthase (FAS) and the
      thermogenic marker UCP. IGF-I-induced differentiation-related gene expression at
      24 h in both primary and immortalized brown adipocytes was mediated by an
      increase in p21ras.GTP active protein content. Transformed cell lines
      overexpressing exogenous p21ras (mainly in its ras.GTP active form)
      constitutively showed a higher lipid content and a higher FAS and UCP mRNA
      expression compared to primary and immortalized cells. These transformed cells
      were IGF-I independent with respect to their studied differentiation-related
      parameters. Additionally, transient transfection of primary brown adipocytes with
      the transforming ras gene induced UCP and FAS mRNA expression as well as
      cotransactivated UCP-chloramphenicol acetyltransferase fusion gene. Moreover, IGF
      I transactivation of UCP promoter was partially precluded by cotransfection with
      the dominant-negative ras gene. Our results strongly suggest that IGF-I/p21ras
      induces adipogenic- and thermogenic-related gene expression in brown adipocytes.

PMID- 8877106
TI  - A comparative study of the hepatic mitogen-activated protein kinase and Jun-NH2
      terminal kinase pathways in the late-gestation fetal rat.
AB  - Mitogen-activated protein kinases (MAPKs) and Jun-NH2-terminal kinases (JNKs) are
      considered members of parallel but separate signal transduction cascades. We have
      compared the regulation and, indirectly, the role of these two pathways in
      hepatic development during late gestation in the rat. Our initial experiments
      showed that the two pathways crossed over to a significant degree. Both could be
      activated in primary cultures of fetal rat hepatocytes by exposure to
      transforming growth factor alpha (TGF-alpha), a potent MAPK activator, or tumor
      necrosis factor alpha (TNF-alpha), a potent JNK activator. Fractionation of fetal
      hepatocyte lysates showed that the same MAPKs were stimulated by TGF-alpha as by
      TNF-alpha. In contrast, TGF-alpha activated only one JNK, whereas TNF-alpha
      stimulated multiple kinases with activity toward Jun. JNKs were found to be
      active under normal conditions in 19-day fetal liver compared with adult liver,
      whereas MAPK was not. Moreover, although JNKs could be activated further by
      intraperitoneal injection of TNF-alpha to the intact 19-day fetus, MAPKs could
      not be activated in vivo by i.p. injection of epidermal growth factor (EGF),
      which, like TGF-alpha, acts via the EGF receptor. EGF could not activate fetal
      hepatic MAPKs even though signal initiation was intact, as indicated by tyrosine
      phosphorylation of the adaptor protein Shc and Shc/Grb2 complex formation. These
      results indicate that the JNK-signaling pathway may support fetal hepatocyte
      proliferation in vivo. In contrast, MAPK signaling is uncoupled, possibly
      indicating that it is not involved in maintaining hepatocyte proliferation in the
      late-gestation rat.

PMID- 8877107
TI  - Characterization of the mouse transforming growth factor alpha gene: its
      expression during eyelid development and in waved 1 tissues.
AB  - The spontaneous mouse waved 1 (wa1) mutation is allelic with the transforming
      growth factor alpha (TGF-alpha) gene and produces phenotypes similar to those of
      TGF-alpha knockout mice. Here, we show that TGF-alpha mRNA and protein levels are
      measurable in wa1 tissues but reduced 5- to 30-fold relative to wild type.
      Because the wa1-coding sequence is identical to that of the normal mRNA, wa1 is
      not a null mutation. Nuclear run-on analyses revealed decreased transcription of
      the TGF-alpha gene in wa1 tissues, but the sequence of a 3.2-kb 5' flanking
      fragment containing the promoter was unaltered. Moreover, pulsed field gel
      electrophoresis analysis did not reveal alterations within 750 kb upstream or 350
      kb downstream of the gene, and chromosome 6 was karyotypically normal. Hence, we
      speculate that the wa1 mutation may be subtle and/or reside at a greater distance
      from the TGF-alpha gene. TGF-alpha deficiency elicits a spectrum of variably
      penetrant eye anomalies in wa1 and knockout mice that are associated with open
      eyes at birth. We found that late-gestation wa1 and TGF-alpha-null embryos
      display a significant delay in eyelid closure, although the eyes of most embryos
      fuse prior to birth. In situ hybridization localized TGF-alpha expression to the
      advancing margins of the eyelid epithelium and epidermal growth factor receptor
      expression throughout the eyelid and corneal epithelia. These results suggest
      that eye problems observed in TGF-alpha-deficient adult mice arise from premature
      exposure and trauma to open eyes during or following parturition.

PMID- 8877108
TI  - Gene localization and expression of thienamycin cyclase gene in Streptomyces
      lividans TK24.
AB  - Transformants of S. lividans TK24 were obtained by transforming a recombinant
      plasmid p6BC12 harboring the thienamycin cyclase gene into it. An antibacterial
      substance could be detected by the conversion of fermentation broth of the Y3
      block mutant and the purified Y3 mutant intermediate with a cell-free extract of
      S. lividans TK24 transformant. Paper chromatographic analysis showed that the
      conversion product of Y3 fermentation broth with cell-free extract of S. lividans
      TK24 was thienamycin and an unstable antibacterial substance was a product of Y3
      intermediate with cell-free extract of the transformants. This result indicated
      that the thienamycin cyclase gene was expressed in S. lividans TK24 and
      complemented the deficiency in the Y3 block mutant. Restriction analysis of
      p6BC12 was carried out and the restriction map was constructed. The thienamycin
      cyclase gene was localized on a 0.9 kb PstI-HinCII fragment from a bioconversion
      result. The 1.0 kb IPNS homologous DNA fragment in plasmid p6BC12 was excluded
      from the cyclase activity.

PMID- 8877109
TI  - YAC cloning and identification of rice (Oriza sativa L.) genomic DNA.
AB  - Construction of the genomic library by using yeast artificial chromosomes (YAC)
      has been an approach to a map-based gene cloning strategy. We have obtained more
      than 2000 YAC clones for the construction of a rice (Oriza sativa L.) genomic
      library through a procedure that could be summarized as follows: a fractionate by
      the pulsed-field gel electrophoresis (PFGE), the rice nucleic high molecular
      weight (HMW) DNA which is partially digested with EcoRI, and recovered fragments
      larger than 200 kb; ligate the fragments to the EcoRI digested YAC vector pairs
      pJS97 and pJS98; transform competent spheroplasts prepared from yeast strain
      YPH252; and select transformants directly on Ura-Trp-double selective media.
      Southern hybridization results indicated that the sizes of inserts were in the
      range of 200-820 kb.

PMID- 8877110
TI  - High level expression of oryzacystatin in Escherichia coli.
AB  - A rice cDNA library of immature seeds has already been constructed, from which
      colonies carrying oryzacystatin cDNA were isolated. The coding region of the
      oryzacystatin (a thiol proteinase inhibitor) gene was amplified by the Polymerase
      Chain Reaction (PCR) and inserted downstream of lambdaPRPL promoter of E. coli
      thermal-inducible expression vector pBV220. An oryzacystatin expression plasmid
      pBVC9 was therefore obtained. Shifting the culture temperature of E. coli DH5
      alpha (pBVC9) from 30 degrees C to 42 degrees C led to a high level expression of
      oryzacystatin. The result of SDS-PAGE showed a distinct band of 12.0 kDa which
      accounts for at least 10% of the total soluble proteins. The inhibitory activity
      of the total soluble proteins of E. coli DH5 alpha (pBVC9) toward papain was
      confirmed by using that of E. coli DH5 alpha (pBV220) as a control.

PMID- 8877111
TI  - Study on the production of human interferon alpha-2b expressed in Escherichia
      coli.
AB  - The production process of human interferon alpha-2b was established in our
      institute. The human interferon alpha-2b was expressed in E. coli by using PL
      promotor. The production process consists of high cell density fermentation,
      refolding of the inclusion bodies, chromatography with Sephadex G-50 and DEAE,
      without using monocloning antibody affinity chromatography. After purification,
      about 500 mg of the human interferon alpha-2b was obtained from 1 kg wet cell
      harvested from 10 L fermentation broth. The biological activity shows 1-2 x 10(8)
      IU/mg protein. This production process is very simple and easy to scale-up. If
      this process adapted, it will save a lot of facility investment, space, and
      labor. Therefore, the cost will be reduced.

PMID- 8877112
TI  - An attempt on using the method of R-Q double-factor analysis to identify and
      group fusants.
AB  - A subsequent numeric taxonomy method for identifying and grouping the fusants was
      explored on the basis of characterization of the protein profiles of the fusants.
      By these two means, several typical excellent candidates of recombinants could be
      searched out quickly. Among the fusants from a definite fusion-cross, the
      different sister-strains were regarded as the samples of observation (n = N), the
      positions of the all bands of protein profiles as the objects (p = P), and the
      photometer-scanning area of the specific band as the experimental value (X) (zero
      was taken when the specific band of a certain strain was absent). The genetic
      multirelationships among the inter- and intra-sister-strains in terms of the
      positions and contents of the protein bands after fusion recombination occurred
      from this definite fusion-cross could therefore be determined on the same
      orientational factor-plate by using the computer program of the R-Q double-factor
      method to analyze this data matrix (Xnxp). These sister-strains could then be
      identified and grouped from the deduced heredity relationship between the fusants
      and parents.

PMID- 8877113
TI  - Agrobacterium tumefaciens mediated transformation of Orychophragmus violaceus
      cotyledon and regeneration of transgenic plants.
AB  - Excised cotyledons of Orychophragmus violaceus were used as explants for tissue
      culture. They were cultured on the MS medium supplemented with BA (3 mg/L) and
      NAA (0.2 mg/L). When the regenerated buds were 2 cm long, they were excised and
      transferred onto 1/2 MS medium with IBA (0.03 mg/L), then the whole plants were
      regenerated. The frequency of plant regeneration was 100%. Subsequently, the
      genetic transformation of O. violaceus was studied. After 2-3 days of
      cocultivation with Agrobacterium tumefaciens strain A208se (pTiT37, pROA93), the
      cotyledons were transferred onto the selection medium containing 25 mg/L Km and
      250 mg/L Ap. After shoots emerged, they were excised and transferred onto the
      rooting medium containing 25 mg/L Km and 100 mg/L Cef. The roots were formed
      within 4-5 weeks. The whole plants were transplanted into pots and grew well. The
      frequency of plant regeneration was about 51%. The regenerated plants showed high
      enzymatic activities of beta-glucuronidase and neomycine phosphotransferase II.
      Southern blot analysis confirmed that NPTII gene had been stably integrated into
      the chromosomal genome of O. violaceus. The transformation frequency was 5.6%.
      The first transgenic plant of O. violaceus is being reported.

PMID- 8877114
TI  - Transformation of Pleurotus sapidus protoplasts by electroporation.
AB  - The total DNA of Pleurotus ostreatus was successfully transferred into the
      protoplasts of monokaryotic mycelia of Pleurotus sapidus by electroporation. The
      transformants were selected by their clamp connection of dikaryocyte, and the
      transformation frequency and transformation rate were 8.2 x 10(-5) and 3.6%,
      respectively. Analyzing the esterase isozyme, it was found that the transformants
      showed some isozyme bands of P. ostreatus and P. sapidus, and new non-parental
      bands. This proved that the recombination occurred between the DNAs of P. sapidus
      and P. ostreatus. The fruit bodies of the transformants showed morphological
      changes.

PMID- 8877115
TI  - Studies on the transfer techniques of three maize genes.
AB  - Maize transformation has been carried out through microprojectile bombardment,
      ultrasonication in a DNA buffer, and ovary-injection with a self-made
      microinjector. The plasmid pB48.415, which carries a 3'-truncated Bt-toxin
      protein gene and a hygromycin phosphotransferase (hpt) gene, was used in the
      transformation. Transgenic maize plants were obtained from immature embryos and
      embryogenic calli bombarded with a particle gun, embryogenic calli ultrasonicated
      under different conditions of ovaries injected 10-20 hours after pollination. The
      results of Dot blotting and Southern blotting analyses proved the integration of
      the Bt gene into maize genome.

PMID- 8877116
TI  - A study of the optimum bacteriostatic action of a synthetic medicine on bacteria
      using a microcalorimetric method.
AB  - The growth thermograms of strain 6, 2b, 3b, 5b, 1a, x, and y of Shigella flexneri
      with the inhibitory action of a synthetic medicine were determined by using the
      2277 thermal activity monitor. Using a microorganism growth model with inhibitory
      conditions, the specific growth rate (mu) at different concentrations (c) of a
      synthetic medicine were calculated and the mu approximately c equations were
      established. From these mu approximately c equations, the concentration of the
      synthetic medicine with which the specific growth rate was minimum could be
      calculated. Therefore, we can analyze the bacteriostatic action of the synthetic
      medicine on these bacteria.

PMID- 8877117
TI  - The expression of locomotor circadian rhythm in female German cockroach,
      Blattella germanica (L.).
AB  - Fifteen percent of intact female German cockroaches (n = 13), Blattella germanica
      (L.) (Dictyoptera: Blattellidae), had weak free-running locomotor rhythmicity
      under 28 degrees C and constant darkness conditions. However, 86% of
      ovariectomized females (n = 14) showed a strong free-running rhythm under the
      same conditions with a circadian period of 23.60 +/- 0.15 h, similar to the
      male's period of 23.45 +/- 0.03 h. In addition, the locomotory activities
      occurred mainly during the subjective night under DD conditions as was the case
      in males. These results indicated that female locomotion was under the control of
      a circadian oscillator, which was masked by the existence of ovaries. This
      internal masking effect could be removed by the existence of males, but females
      had no effect on the locomotor pattern of another female. Since the male failed
      to entrain female locomotion, its role as a zeitgeber was excluded. That the
      locomotory pattern of the females still coincided with their reproductive cycle
      when exposed to male odor suggests that exposure to a male only partially removed
      the internal masking effects.

PMID- 8877118
TI  - Circadian pattern of cercarial emergence in Schistosoma mansoni
      (Platyhelminthes:Digenea) from isolated Biomphalaria glabrata.
AB  - The present work aimed to compare the acrophases (peak hours) of emergence of
      Schistosoma mansoni cercariae among isolated individuals of the snail
      Biomphalaria glabrata. Laboratory stocks of melanic B. glabrata from the same
      biotope as the S. mansoni strain (Belo Horizonte, Minas Gerais) were used. Twenty
      two snails individually exposed to five miracidia were tested. Chronobiological
      trials were performed outdoors after an acclimation period of at least a week.
      Three groups of snails were tested between November 1989 and April 1991.
      Cercarial emergence from individual isolated snails was quantified every 3 h for
      3 consecutive days. In all trials, most cercariae were found to emerge during
      daytime (94.9%). Time series and chronograms showed recurrent peaks during the
      daytime. The periodogram suggested that 24 h was the period that best fitted
      cercarial emergence data in 90.9% of the snails. The single cosinor analysis
      confirmed 24-h rhythms in 95.5% of the snails. Acrophases of cercarial emergence
      among individual snails occurred between 14:15 and 17:02. They did not differ
      significantly. The population cosinor analysis indicated greater homogeneity in
      the 24-h rhythms of cercarial emergence than in the snail groups of each
      chronobiological trial. Acrophases of cercarial emergence occurred between 14:53
      and 15:27 and did not differ significantly among all trials. Data from the three
      trials were pooled and analyzed using the population cosinor. This statistical
      method indicated a homogeneity in the 24-h rhythms of cercarial. emergence from
      all snails, with acrophase occurring around 15:00. Results showed that the
      acrophases of cercarial emergence of S. mansoni are similar among isolated B.
      glabrata specimens. Data support the hypothesis of a "gate" rhythm in the
      dynamics of cercarial production and emergence. It is suggested that the adaptive
      importance of the "gate" mechanism is associated with the concentration of
      cercariae in the water at times when the vertebrate is present, optimizing the
      contact between the parasite and the host. The emergence of some cercariae at
      night (5.1% of the total number of emerged cercariae) suggests a flexible "gate"
      that could be associated with a residual light effect or with experimental
      procedures in the laboratory.

PMID- 8877119
TI  - Responses of the circadian locomotor activity rhythm of Mus booduga to shifts in
      LD schedules.
AB  - The responses of the field mouse Mus booduga to shifts in schedules of LD cycles
      were monitored and the results were interpreted with the help of a PRC
      constructed for the same species. The results reveal that, M. booduga reentrained
      faster with a lesser number of transients after delay shifts than advance shifts,
      thus exhibiting "asymmetry effect." A positive correlation was observed between
      the number of transients and the number of hours of shift. In most of the shifts,
      the sign of the transients (negative for delaying transients and positive for
      advancing transients) coincided with the direction of the shift. Interestingly,
      11 and 12 h of advance shifting resulted in delaying transients. An 11-h advance
      shift can also be interpreted as a 13-h delay. Reentrainment through delaying
      transients is faster as compared to reentrainment through advancing transients.
      Thus, this animal might have taken a "shorter route," as proved by the fact that
      an 11-h advance shift has evoked delaying transients. But a 13-h advance shift
      evoked only advancing transients. This prompts us to speculate that there may be
      a "phase jump" in M. booduga. Further, irrespective of whether L or D has been
      doubled in a 12-h shift, both evoked only delaying transients.

PMID- 8877120
TI  - Day-night treatment difference of tobramycin serum and intrarenal drug
      distribution and nephrotoxicity in rats: effects of fasting.
AB  - The effects of short-term food deprivation on the serum and renal distribution
      and nephrotoxicity of tobramycin were studied in female Sprague-Dawley rats
      maintained on a 14-h light/10-h dark cycle (light on: 06:00). For the
      distribution study, a single injection of tobramycin (40 mg/kg, i.p.) was
      administered at 14:00 or 02:00 to normally fed animals or to animals fasted for
      12 h before tobramycin injection; these treatment times correspond to the peak
      and trough of tobramycin nephrotoxicity as previously determined in other
      studies. The serum and cortical levels of tobramycin were significantly higher
      60, 120, and 240 min after the injection in fasted animals treated at 02:00
      compared with normally fed animals treated at the same time (p < 0.05). In
      animals injected at 14:00, similar levels of tobramycin were measured in both
      fasted and fed rats. In the nephrotoxicity study, female Sprague-Dawley rats were
      fasted for 12 h before and 24 h after the timed single injection of tobramycin
      (150 mg/kg, i.p.). The 24-h urinary excretion of beta-galactosidase was
      significantly higher in fasted animals treated at 02:00 than in fed rats treated
      at the same time of day. Seventy-two hours following tobramycin injection, serum
      creatinine levels and cortical levels of tobramycin were significantly higher in
      fasted rats treated at 14:00 than at 02:00 and in fed rats treated at 14:00.
      These data suggest that a short period of food deprivation modulates the temporal
      variations of tobramycin nephrotoxicity.

PMID- 8877121
TI  - Circadian determinants of the postlunch dip in performance.
AB  - This study compared rectal temperature rhythms in groups of subjects who either
      did (n = 5) or did not (n = 7) show a clear postlunch dip in performance at a
      monotonous (25-30 min) vigilance task. Performance was tested every 2h in a
      standardized routine with lunch replaced by hourly liquid food supplements. Those
      showing the postlunch performance dip had a higher amplitude and later peaking
      12h component to their rectal temperature rhythm that those who did not,
      resulting in flat, rather than rising, temperatures over the 10:00-15:00 time
      interval. The effect could not be explained by intergroup differences in prior
      sleep, morningness, or gender, although there was a trend (p = 0.09) for the
      "dip" group to be slightly younger (21.8y vs. 24.2y). The postlunch dip appears
      to be an endogenous phenomenon individually determined, but related to the
      strength of the (12h) harmonic of the circadian system.

PMID- 8877122
TI  - Diurnal rhythm of the muscular performance of elbow flexors during isometric
      contractions.
AB  - The influence of time of day on elbow flexion torque was studied. Thirteen
      physical education students, 7 males and 6 females, made maximal and submaximal
      isometric contractions at 90 degrees of elbow flexors using a dynamometer. The
      torque developed was measured on each contraction. The myoelectric activity of
      the biceps muscle was also measured at the same time by surface electromyography
      (EMG) and quantified from the root mean square (RMS) activity. Torque and surface
      EMGs were measured at 6:00, 9:00, 12:00, 15:00, 18:00, 21:00, and 24:00 h over
      the same day. Oral temperature before each test session was measured on each
      occasion after a 30-min rest period. We observed a diurnal rhythm in elbow flexor
      torque with an acrophase at 18:00 h and a bathyphase at 6:00 h, in phase with the
      diurnal rhythm in oral temperature. However, the diurnal rhythm of temperature
      did not appear to have any influence on the torque. Links between neuromuscular
      efficiency and RMS/torque ratio were evaluated by measuring muscle activity along
      with torque. We also assessed variations in the level of maximal activity of the
      muscle under maximal voluntary contraction. Neuromuscular efficiency fluctuated
      during the day, with maximal and minimal efficiency at 18:00 h and 9:00 h,
      respectively, whereas activation level was maximal at 18:00 h and minimal at 9:00
      h. The diurnal rhythm of torque was accounted for by variations in both central
      nervous system command and the contractile state of the muscle.

PMID- 8877123
TI  - Immunoblot analysis of anti-Ureaplasma urealyticum antibody in pregnant women and
      newborn infants.
AB  - The purpose of the present study was to determine the frequency in which antibody
      reactive to Ureaplasma urealyticum could be detected in a population of pregnant
      women and newborn infants. Serum samples from a prospective cohort of 80 healthy,
      U. urealyticum culture-positive and culture-negative pregnant women and a
      retrospective cohort of 522 infants born at between 25 and 42 weeks of gestation
      were studied by immunoblot analysis. Cultures of specimens from the lower genital
      tract were positive for U. urealyticum for 83% of the pregnant women, and serum
      immunoglobulin G (IgG) antibody which reacted to U. urealyticum was detectable in
      93% of the pregnant women. Samples from five women (8%) had increases in the
      number of anti-U. urealyticum IgG bands over the course of the pregnancy. Samples
      from four of these five women had corresponding increases in the number of
      antibody bands present in IgA immunoblots. Six of the 522 samples from newborns
      or cord blood (1.1%) were positive for anti-U. urealyticum IgA; 5 of these 6
      samples were also positive for IgM. The six anti-U. urealyticum IgA-positive
      infants were distributed as follows; 3 of 67 (4.5%) infants were delivered at 25
      to 30 weeks of gestation, 3 of 176 (1.7%) infants were delivered at 31 to 34
      weeks of gestation, and 0 of 279 infants were delivered at > or = 35 weeks of
      gestation. An antibody response to U. urealyticum can be detected in pregnant
      women and preterm infants and may serve as a marker of infection.

PMID- 8877124
TI  - Type 1 and type 2 cytokine profiles in children exposed to or infected with
      vertically transmitted human immunodeficiency virus.
AB  - In human immunodeficiency virus (HIV)-infected adults, cytokine production
      profiles switch from predominantly type 1 (interleukin-2 [IL-2] and gamma
      interferon [IFN-gamma]) to type 2 (IL-4 and IL-10) cytokines with disease
      progression. To test this hypothesis in vertically HIV-infected children, we
      measured cytokine transcription and production in rapid progressors (RPs),
      seroreverters (SRs), and those children exposed to HIV in utero (P0s). Production
      of type 1 and type 2 cytokines was measured in peripheral blood mononuclear cell
      cultures of 8 SR, 25 P0, and 11 RP children. Unstimulated cultures, irrespective
      of infection and stage of disease, produced similar levels of IL-2, IFN-gamma, IL
      4, and IL-10. Upon stimulation with phytohemagglutinin (PHA) plus phorbol-12
      myristate-13-acetate (PMA), RP children produced less IL-2 (P < 0.01) and IFN
      gamma (P < 0.02) than SR children and also expressed significantly less IFN-gamma
      mRNA (P < 0.01) than SR children. RP children expressed significantly higher
      levels of IL-4 mRNA than P0 children (P < 0.03). There were no differences in the
      production of IL-10 by PHA-PMA-stimulated peripheral blood mononuclear cell
      cultures among the three groups of children. Our data with these pediatric
      patients suggest that a deficiency in mitogen-stimulated type 1 cytokine
      production and excess type 2 cytokine (IL-4) transcription correlate with disease
      progression. Additional studies with larger sample sizes are needed to test
      further the hypothesis of the type 1-to-type 2 cytokine switch in children
      infected with HIV.

PMID- 8877125
TI  - Antibody responses against the G and F proteins of bovine respiratory syncytial
      virus after experimental and natural infections.
AB  - Antibodies against the two major surface glycoproteins of bovine respiratory
      syncytial virus (BRSV), G and F, play a role in protection against BRSV
      associated disease, but only the antibody response against the F protein has been
      well described. Therefore, we used a novel peptide-based enzyme-linked
      immunosorbent assay (G peptide-ELISA) to compare immunoglobulin G (IgG) and IgG
      subclass antibody responses against the G protein with the antibody response
      against the F protein, as measured by a conventional BRSV ELISA (F-ELISA).
      Experimental infection of cattle induced significantly lower antibody titers than
      did natural infection. After natural primary infection, G peptide-specific
      antibodies declined more rapidly and to lower levels than the F protein-specific
      antibodies. As a consequence, the G peptide-ELISA detected more reinfections than
      did the F-ELISA. Ratios of G- and F-specific IgG1/IgG2 antibody titers did not
      differ markedly after infection or vaccination. Interestingly, after natural
      infection calves did not develop an IgG2 response to the complete G protein. In
      contrast, adult cattle had high IgG2 titers against this protein. Vaccination
      with a live vaccine induced low antibody titers, similar to the titers after
      experimental infection, whereas vaccination with an inactivated vaccine induced
      high titers. The results indicate that the kinetics of the G- and F-specific
      antibody responses differ. Furthermore, the IgG subclass response against the
      unglycosylated central region of the G protein is similar to the IgG subclass
      response to the F protein, but the IgG subclass response differs from the
      response to the complete G protein.

PMID- 8877126
TI  - Increasing doses of purified influenza virus hemagglutinin and subvirion vaccines
      enhance antibody responses in the elderly.
AB  - The reactogenicities and immunogenicities of two influenza virus vaccines were
      compared in a placebo-controlled clinical trial among healthy ambulatory persons
      > or = 65 years old (mean age, 72 years). Volunteers were assigned randomly to
      receive 15-, 45-, or 135-micrograms doses of monovalent influenza A/Taiwan (H1N1)
      hemagglutinin (HA) or subvirion (SV) vaccine intramuscularly or a placebo.
      Increasing doses of SV vaccine were associated with a higher rate of injection
      site discomfort (P < 0.05; chi-square test for linear trend), but all doses of
      both vaccines were well tolerated. Increasing the dose of the HA or the SV
      vaccine resulted in increasingly higher postimmunization levels of serum
      hemagglutination inhibition and neutralizing antibody levels (P < 0.001; multiple
      linear regression). Mean serum antibody titers at 1 month increased two- to
      threefold with a ninefold increase in dose; the frequencies of fourfold or
      greater rises in titer likewise increased. An increase in the dose of the HA or
      the SV vaccine also resulted in increased frequencies of rises in immunoglobulin
      A or G antibody titers in nasal wash specimens. The frequencies increased
      approximately twofold for each vaccine with a ninefold increase in the dose.
      These data suggest that increasing the HA vaccine dose is a promising approach to
      the development of improved influenza virus vaccines for use in elderly people.

PMID- 8877127
TI  - Neuraminidase-specific antibody responses to inactivated influenza virus vaccine
      in young and elderly adults.
AB  - Little information is available on the potential role of antibody to influenza
      virus neuraminidase (NA) in vaccine-induced immunity. In the present study,
      serologic responses to the N1Texas/91 and N2Beijing/92 NA components of trivalent
      inactivated influenza virus vaccine were measured by NA inhibition (NI) and
      enzyme-linked immunosorbent assay (ELISA), and the results for adults aged 18 to
      45 (young) or > or = 65 (elderly) years were compared. The two age groups had
      comparable rates (32 to 50%) of NI response. In contrast, ELISA immunoglobulin G
      (IgG) antibody responses to N1 and N2 NAs occurred in 70 to 71 and 67 to 83%,
      respectively, of young subjects but in only 3 to 18 and 18 to 35%, respectively,
      of elderly subjects. prevaccination mean ELISA IgG and IgA NA antibody titers
      were generally lower for the young adults than they were for the elderly, whereas
      the corresponding NI titers were comparable. In young adults, plaque size
      reducing NA antibody increases were positively associated with ELISA but not with
      NI antibody increases. There were no apparent age-related differences in the
      immunoglobulin isotype distribution of the anti-NA response, with IgG being the
      dominant class and IgG1 the dominant subclass of serum antibody. Anti
      hemagglutinin antibody responses to H1Texas/91 and H3Beijing/92 were greater in
      magnitude and frequency than the corresponding NA-specific responses to
      N1Texas/91 and N2Beijing/92 when measured by hemagglutination inhibition and NI,
      respectively, but not when measured by ELISA. The discordance between NI and
      ELISA for measurement of NA-specific vaccine responses may reflect the relative
      insensitivity of NI in discriminating differences when initial antibody titers
      are low.

PMID- 8877129
TI  - Mapping of the H7-serospecific domain of Escherichia coli flagellin.
AB  - The amino acid sequences responsible for H7 and H23 flagellum serology have been
      identified by using a genetic approach. The H7-specific domain was located
      between amino acids 352 and 374 of the H7 flagellin. The sequencing data also
      demonstrated that the difference between the H7 and H23 flagellins in this region
      results from a single substitution at amino acid 366 (Ser-->Thr). The common
      epitopes for H7 and H23 were located between amino acids 284 and 366.

PMID- 8877128
TI  - Clonal diversity of Streptococcus mitis biovar 1 isolates from the oral cavity of
      human neonates.
AB  - The clonal diversity of 101 isolates of the pioneer bacterium Streptococcus mitis
      biovar 1 obtained from the oral cavities of 40 human neonates 1 to 3 days, 2
      weeks, and 1 month postpartum was examined by using rRNA gene restriction
      patterns. There was a high degree of genetic diversity, with the 101 isolates
      comprising 93 unique PvuII ribotypes. There were eight identical pairs of
      ribotype patterns, and seven of the eight pairs were obtained from individual
      neonates. Only one identical pair comprised isolates obtained from different
      neonates. In all but two cases, isolates with matching ribotypes were obtained at
      one visit. Two pairs of isolates with matching ribotype patterns were obtained
      from neonates on successive visits. The ribotype patterns of the isolates were
      examined by cluster analysis. The isolates forming each cluster were very
      similar, yet each cluster was well separated from its neighbors. When several
      isolates were obtained from individual neonates at a particular visit, in some
      instances they were contained in a single cluster, whereas in other cases each
      isolate was contained in a separate cluster. Isolates obtained from individual
      neonates on successive visits tended to be contained in different clusters. This
      high degree of diversity, which has been observed in other mucosal commensal
      bacteria, may serve as a mechanism for avoiding immune elimination of these
      bacteria.

PMID- 8877130
TI  - Chemiluminescent and flow cytometric analysis of gamma interferon preincubation
      on neonatal and adult rat polymorphonuclear leukocytes.
AB  - Gamma interferon (IFN-gamma) has multiple immunomodulating effects and has been
      postulated as a possible immunopotentiating agent for the prevention or treatment
      of neonatal infections. This report describes the effect of rat recombinant IFN
      gamma on the oxidative burst activity and CD11b expression of neonatal and adult
      rat polymorphonuclear leukocytes (PMNL). Oxidative burst activity was assessed by
      chemiluminescence and dihydrorhodamine flow cytometry. Neonatal PMNL exhibited
      significantly less oxidative burst activity than did adult PMNL. IFN-gamma mildly
      enhanced the chemiluminescence response of PMNL from both the rat pups and
      adults, but this effect was not statistically significant when analyzed by a
      multivariate model of repeated-measures analysis of variance for both
      chemiluminescence and dihydrorhodamine flow cytometry. CD11b expression was also
      not significantly enhanced by IFN-gamma.

PMID- 8877131
TI  - Physical mapping of the Borrelia miyamotoi HT31 chromosome in comparison with
      that of Borrelia turicatae, an etiological agent of tick-borne relapsing fever.
AB  - We report the construction of physical maps of chromosomes for Borrelia miyamotoi
      HT31 (a new species of Borrelia) and Borrelia turicatae (relapsing fever agent)
      by pulsed-field gel electrophoresis of DNA fragments generated by digestion of
      chromosomal DNA with rare-cutting restriction endonucleases and reciprocal
      hybridization. The size of the B. miyamotoi HT31 chromosome was calculated to be
      approximately 925 kilobase pairs, and the chromosome for B. turicatae was
      estimated to be 951 kilobase pairs. The chromosomes of B. miyamotoi HT31 and B.
      turicatae consisted of single linear molecules. The locations of several genes
      have been assigned to the chromosome maps by Southern hybridization by using
      specific gene probes. Comparison of the genetic maps of the two species of
      Borrelia provided evidence that the gene order on the chromosomes is quite
      similar to that of Borrelia burgdorferi sensu lato strains and is highly
      conserved in the genus Borrelia.

PMID- 8877132
TI  - Purification of Mycobacterium bovis BCG Tokyo antigens by chromatofocusing,
      lectin-affinity chromatography, and hydrophobic interaction chromatography.
AB  - A combination of chromatofocusing, lectin-affinity chromatography, and
      hydrophobic interaction chromatography resulted in a simple purification of
      protein antigens of Mycobacterium bovis BCG Tokyo culture filtrate.
      Identification was established on the basis of chromatographic separation, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis determination of molecular
      weights, and N-terminal amino acid determination. Chromatofocusing on PBE 94
      accomplished the separation of BCG85B from other BCG85 complex antigens and
      partial separation of MPB64 and MPB70 antigens. Subsequently, MPB64 and MPB70
      were completely separated on a high-performance liquid chromatography TSK Phenyl
      5PW hydrophobic interaction chromatography column. This column also separated
      BCG85B from a 17-kDa protein with an N-terminal amino acid sequence of A-V-P-I-T
      G-K-L-G-S-E-L-T-M-T-D-( )-V-G-Q, which is similar to the sequence of MPT63.
      Concanavalin A-Sepharose-affinity chromatography separated MPB64 from a 43- and
      47-kDa doublet with an amino acid sequence of D-P-E-P-A-P-P-V-P-P-V-P-A-( )-A-A-S
      P, which is similar to the sequence of MPT32 and which appears to be
      glycosylated.

PMID- 8877133
TI  - Differential effects of interleukin-12, interleukin-15, and interleukin-2 on
      human immunodeficiency virus type 1 replication in vitro.
AB  - Cytokines may have clinical utility as therapeutic agents for human
      immunodeficiency virus type 1 (HIV-1) infection and as an adjuvant for vaccines.
      The effect of interleukin-12 (IL-12) and IL-15 on in vitro HIV-1 replication was
      investigated. IL-12 and IL-15 at doses up to 10 ng/ml had little effect on basal
      HIV-1 p24 antigen production by chronically HIV-infected T (ACH-2) and monocytic
      (U1) cell lines. For ACH-2 cells stimulated with phorbol 12-myristate 13-acetate
      (PMA; 50 ng/ml), IL-12 and IL-15 significantly increased p24 antigen production
      by 20 and 30%, respectively (n = 6). In contrast, IL-12 and IL-15 (10 ng/ml)
      treatment of PMA-stimulated U1 cells decreased p24 antigen production by 16 and
      15%, respectively (n = 6). We next studied the effect of IL-12 and IL-15 on HIV
      infected peripheral blood mononuclear cells (PBMCs). In 10 HIV-seropositive
      patients' PBMCs cocultured with mitogen-activated HIV-seronegative donor cells,
      two patterns of p24 antigen production were observed in response to IL-2: low
      (p24 antigen production < 10(3) pg/ml; n = 8) and high (p24 antigen production >
      10(3) pg/ml; n = 2) response. For the low-response pattern, IL-12 and IL-15
      increased viral replication by 97-fold and 100-fold, respectively (P = 0.05 and
      0.004, respectively). For the high-response pattern, both IL-12 and IL-15
      suppressed HIV replication. The effect of IL-2, IL-12, and IL-15 on acute in
      vitro infection by HIV-1JRCSF was also examined. IL-12 did not increase p24
      antigen production above basal levels while IL-2 and IL-15 significantly enhanced
      p24 antigen production (by approximately 2-fold). In conclusion, IL-12 and IL-15
      may have differential effects on latent and acute HIV infection, and their
      ability to enhance HIV production may depend on cell activation. Thus, the use of
      these cytokines may be dictated by the clinical state of the patient.

PMID- 8877135
TI  - Comparison of two 2,3-diacyl trehalose antigens from Mycobacterium tuberculosis
      and Mycobacterium fortuitum for serology in tuberculosis patients.
AB  - Immunoglobulin G antibodies against two 2,3-diacyl trehalose (DAT) antigens from
      Mycobacterium tuberculosis (DATT) and Mycobacterium fortuitum (DATF) were studied
      by enzyme-linked immunosorbent assay of 356 serum samples. The sera were obtained
      from non-tuberculosis-infected individuals (282 serum samples) and tuberculosis
      patients (74 serum samples). Non-tuberculosis-infected individuals were healthy
      people (120 serum samples; positive purified-protein-derivative skin test, 60
      patients; negative purified-protein-derivative skin test, 60 patients) patients
      with nontuberculosis lung disease (59 serum samples), contacts of sputum-smear
      positive tuberculosis patients (57 serum samples), and human immunodeficiency
      virus-infected patients with nontuberculosis lung disease (46 serum samples). Of
      the 74 patients with tuberculosis, 14 were human immunodeficiency virus infected.
      The sensitivity of the method using DATT was 44.5%, and that with DATF was 48.6%.
      The specificities with both antigens were 99.1%. There were no significant
      differences between the mean values for both antigens (P = 0.2815). We therefore
      concluded that both antigens were interchangeable. As M. fortuitum, a fast
      growing mycobacterium, could be a good source of antigen DAT, these results
      deserve consideration in the serology of tuberculosis.

PMID- 8877134
TI  - Prevalence of antibodies to feline parvovirus, calicivirus, herpesvirus,
      coronavirus, and immunodeficiency virus and of feline leukemia virus antigen and
      the interrelationship of these viral infections in free-ranging lions in east
      Africa.
AB  - While viral infections and their impact are well studied in domestic cats, only
      limited information is available on their occurrence in free-ranging lions. The
      goals of the present study were (i) to investigate the prevalence of antibodies
      to feline calicivirus (FCV), herpesvirus (FHV), coronavirus (FCoV), parvovirus
      (FPV), and immunodeficiency virus (FIV) and of feline leukemia virus (FeLV)
      antigen in 311 serum samples collected between 1984 and 1991 from lions
      inhabiting Tanzania's national parks and (ii) to evaluate the possible biological
      importance and the interrelationship of these viral infections. Antibodies to
      FCV, never reported previously in free-ranging lions, were detected in 70% of the
      sera. In addition, a much higher prevalence of antibodies to FCoV (57%) was found
      than was previously reported in Etosha National Park and Kruger National Park.
      Titers ranged from 25 to 400. FeLV antigen was not detectable in any of the serum
      samples. FCoV, FCV, FHV, and FIV were endemic in the Serengeti, while a transient
      elevation of FPV titers pointed to an outbreak of FPV infection between 1985 and
      1987. Antibody titers to FPV and FCV were highly prevalent in the Serengeti (FPV,
      75%; FCV, 67%) but not in Ngorongoro Crater (FPV, 27%; FCV, 2%). These
      differences could be explained by the different habitats and biological histories
      of the two populations and by the well-documented absence of immigration of lions
      from the Serengeti plains into Ngorongoro Crater after 1965. These observations
      indicate that, although the pathological potential of these viral infections
      seemed not to be very high in free-ranging lions, relocation of seropositive
      animals by humans to seronegative lion populations must be considered very
      carefully.

PMID- 8877136
TI  - Humoral antibody to Mobiluncus curtisii, a potential serological marker for
      bacterial vaginosis.
AB  - While bacterial vaginosis (BV) is a polymicrobial syndrome, Mobiluncus spp. are
      the organisms most highly associated with this condition. It is possible that
      serum antibody to Mobiluncus spp. could be used as a serological marker for BV.
      Using immunofluorescence techniques, we studied the prevalence of antibody to M.
      curtisii among three cohorts-pregnant women, pediatric patients, and sexually
      inexperienced women. The prevalence of antibody in each of these three groups was
      75, 6, and 0%, respectively. Of the three pediatric patients with antibody to
      Mobiluncus curtisii, two were neonates, and the only class of antibody detected
      was immunoglobulin G. Among the cohort of pregnant women, the presence of
      antibody could not be correlated with a clinical history of BV. Serum antibody to
      M. curtisii could be a useful serological marker for BV. The lack of correlation
      of antibody positivity to historical information regarding BV suggests that
      unrecognized or undiagnosed episodes of BV may be common.

PMID- 8877137
TI  - Extracellular proteinase activity of Cryptococcus neoformans.
AB  - Extracellular proteinase activity was studied for eight strains of Cryptococcus
      neoformans var. neoformans and two strains of Cryptococcus neoformans var.
      gattii. Proteinase activity was measured by protein agar clearance, azoalbumin
      hydrolysis, gelatin liquefaction, and protein substrate polyacrylamide gel
      electrophoresis. All strains of C. neoformans produced extracellular proteolytic
      activity. Maximal extracellular proteinase activity in supernatants of C.
      neoformans cultures was associated with late logarithmic- and stationary-phase
      cultures. C. neoformans was able to utilize murine immunoglobulin G1, bovine
      immunoglobulin G, and human complement factor 5 for growth in media containing
      these proteins as the sole sources of carbon and nitrogen, suggesting a capacity
      to degrade immunologically important proteins. Protein substrate polyacrylamide
      gel electrophoresis revealed several bands with proteolytic activity at apparent
      molecular masses of 200, 100, and 50 kDa. The results confirm the existence of
      extracellular proteinase activity for C. neoformans.

PMID- 8877138
TI  - Investigation of immunofluorescence cross-reactions against Trichinella spiralis
      by western blot (immunoblot) analysis.
AB  - Immunofluorescence cross-reactions in Trichinella spiralis serodiagnosis are
      sometimes difficult to identify. We compared the results of an indirect
      immunofluorescence assay and the profiles obtained by Western blot (immunoblot)
      analysis for three groups of patients: 10 T. spiralis-infected patients, 10
      patients with autoimmune diseases, and 7 patients with parasitic diseases other
      than trichinellosis. The degree of immunofluorescence cross-reaction was
      variable. Western blotting allowed us to differentiate Trichinella infection from
      other parasitic diseases. In 3 of 10 serum samples from patients with autoimmune
      diseases, bands which had the same sizes as Trichinella bands were observed, and
      they could correspond to shared epitopes such as heat shock proteins.

PMID- 8877139
TI  - Effect of nicotine on secretory component synthesis by secretory epithelial
      cells.
AB  - Previously, we reported that secretory component (SC), lactoferrin (LF), and
      lysozyme (LY) levels were significantly lower in saliva from smokeless tobacco
      (ST) users than in saliva from control non-tobacco users. However, the levels of
      salivary immunoglobulin A were significantly higher, albeit with an altered
      attachment of SC, in ST users than in control subjects. SC, LF, and LY are
      synthesized by secretory epithelial cells at mucosal sites adjacent to lymphocyte
      regions. In the present report, HT-29 human epithelial cells, cultured with
      various concentrations of an ST aqueous extract or pure nicotine (0 to 1 mg/ml)
      or cotinine (0 to 5 mg/ml), exhibited significantly lower levels of cell
      associated cell lysate (CL) and secreted culture supernatant (CS) SC, LF, and LY
      than cells cultured without ST components. Nicotine significantly decreased (P <
      or = 0.05) the synthesis of SC by 20 to 100%, LF by 20 to 60%, and LY by 5 to 75%
      of CL and CS control values. Studies also indicated significant decreases (P < or
      = 0.05) in SC, LF, and LY levels in both CL and CS of cells cultured with ST
      aqueous extract or cotinine. Total cell numbers and metabolic activity
      significantly decreased primarily when cells were incubated with higher
      concentrations of ST extract, nicotine, or cotinine. The addition of human
      recombinant interleukin-4 or gamma interferon diminished the effects ST had on HT
      29 cell synthesis of SC, LF, and LY. Our data indicate that nicotine, cotinine,
      and ST have an adverse effect on synthesis and secretion of SC, LF, and LY. These
      effects were below ST concentrations found to be cytotoxic for secretory
      epithelial cells. Furthermore, addition of interleukin-4 or gamma interferon
      reduced the suppressive effect of ST on synthesis or secretion of SC, LF, or LY.

PMID- 8877140
TI  - Specificity of monoclonal antibodies elicited by mucosal infection of BALB/c mice
      with virulent Shigella flexneri 2a.
AB  - Protective immunity against shigellosis is thought to be determined by the O
      antigen side chains of the lipopolysaccharide (LPS) molecule. To study possible
      common protective epitopes, monoclonal antibodies reacting with Shigella flexneri
      2a LPS were generated from BALB/c mice infected ocularly with the virulent
      serotype 2a strain S. flexneri 2457T and tested against a panel of S. flexneri
      LPSs by enzyme-linked immunosorbent and immunoblot assays. Four monoclonal
      antibodies were identified, all of which showed restricted specificity patterns.
      Three different patterns of reactivity to LPS possessing the 3,4 group antigen
      were seen: (i) 2a only, (ii) 2a and 5a, and (iii) 2a, 4a, 5a, and Y. These
      results have implications for designing a Shigella vaccine that will be
      protective against related serotypes. Electron microscopy studies showed that the
      monoclonal antibodies bind to the bacterial surface in a patchy pattern,
      suggesting their potential use for examining the LPS distribution on the surface
      of the bacteria.

PMID- 8877141
TI  - Unusually high seroprevalence of Borna disease virus in clade E human
      immunodeficiency virus type 1-infected patients with sexually transmitted
      diseases in Thailand.
AB  - The seroprevalence of Borna disease virus (BDV) in human immunodeficiency virus
      type 1-infected individuals in Thailand was examined by using recombinant BDV
      p24. A high (38 to 48%) rate of seroprevalence of BDV was observed in clade E
      infected patients with sexually transmitted diseases, compared with those in
      clade E-infected prostitutes (8.3%), pregnant women (0%), clade B-infected
      intravenous-drug users (0%), and human immunodeficiency virus type 1-negative
      blood donors (1.9%).

PMID- 8877142
TI  - Identification of serum and urine proteins responsible for enhanced pigment
      production by group B streptococci as amylases.
AB  - The serum and urine proteins responsible for enhanced pigment production in
      Streptococcus agalactiae in culture media were purified by chromatography and
      were identified as amylases by comparison of their amino acid composition with
      that calculated for proteins with known sequences. Similar pigment-enhancing
      activity was displayed by other amylases of nonanimal origin and by
      maltooligosaccharides.

PMID- 8877143
TI  - Detection of serum immunoglobulin M to human cytomegalovirus by western blotting
      correlates better with virological data than detection by conventional enzyme
      immunoassay.
AB  - Western blotting (immunoblotting) with proteins separated from purified human
      cytomegalovirus (HCMV) particles (viral WB) has repeatedly been shown to be a
      reliable and sensitive method for detecting HCMV-specific immunoglobulin M (IgM).
      The aim of the present work was to determine whether IgM detected by viral WB
      correlates with virological diagnosis better than conventional enzyme immunoassay
      (conv-EIA). The presence of an active HCMV infection was documented on the basis
      of isolation of virus from urine and/or saliva and on the basis of antigenemia
      and/or PCR with polymorphonuclear leukocytes for immunocompetent and
      immunocompromised subjects, respectively. The agreement observed between IgM
      detected by viral WB and the results obtained by virological detection of HCMV
      was significantly higher (88.7%) than the agreement of IgM detected by conv-EIA
      and virological results (67.5%).

PMID- 8877144
TI  - A rapid and gentle method for isolation of genomic DNA from pathogenic Nocardia
      spp.
AB  - The lack of simple and efficient methods for extraction of DNA from Nocardia spp.
      has hampered molecular manipulation of the DNA for diagnostic purposes. In the
      present study, a method for the rapid extraction of undegraded genomic nocardial
      DNA was established. Briefly, 14 pathogenic Nocardia strains were grown at 37
      degrees C for 3 to 5 days in Sauton broth containing 0.05% Tween 80.
      Subsequently, the cultures were treated for 48 h with 1.2 mg of cycloserine per
      ml (final concentration). Cells were then harvested by centrifugation and treated
      with a lysis solution containing 3 mg of lysozyme per ml. This was followed by
      the addition of proteinase K and sodium dodecyl sulfate to final concentrations
      of 0.2 mg/ml and 0.5%, respectively, and incubation for 1 h at 50 degrees C. DNA
      was precipitated with isopropanol after phenol-chloroform-isoamyl alcohol
      extractions and RNase treated before being quantitated and analyzed by agarose
      gel electrophoresis. The average undegraded DNA yields obtained were 101
      micrograms for Nocardia brasiliensis and 121 micrograms for N. asteroides. This
      DNA was suitable for restriction endonuclease digestion and PCR amplification,
      which are methods being applied to the characterization and diagnosis of slowly
      growing organisms such as Nocardia spp.

PMID- 8877145
TI  - Effect of Clostridium difficile toxin A on CD11/CD18 expression in vitro.
AB  - Clostridium difficile toxin A is chemotactic for neutrophils and induces their
      emigration into the colonic mucosae of rodents. We found that toxin A did not
      upregulate neutrophil beta 2 integrins on isolated human neutrophils. These data
      support the hypothesis that in C. difficile colitis, these adhesion molecules are
      upregulated by endogenous mediators.

PMID- 8877146
TI  - Monoclonal antibodies to the enterotoxin of Bacteroides fragilis: production,
      characterization, and immunodiagnostic application.
AB  - A monoclonal antibody, ICT11, specific for the toxin of enterotoxigenic
      Bacteroides fragilis (ETBF) neutralized the cytotoxic effect of the toxin on
      human colonic cell line HT-29/C1. In an evaluation using 115 diarrheal stool
      specimens and culture as the "gold standard," the assay showed a sensitivity of
      85% and a specificity of 100%. An ICT11-based sandwich enzyme-linked
      immunosorbent assay showed a sensitivity of 100% and a specificity of 98% for
      direct detection of toxin from stool samples compared with those of culture.
      Thus, ICT11-based assays will be useful for screening for ETBF.

PMID- 8877147
TI  - Lymphocyte subset diversity in idiopathic CD4+ T lymphocytopenia.
AB  - The clinical and public health importance of CD4+ T lymphocytopenia without human
      immunodeficiency virus infection is still unclear. We describe herein two new
      human immunodeficiency virus-negative patients with low numbers of peripheral
      CD4+ T cells and opportunistic infections (cerebral toxoplasmosis and
      tuberculosis plus extrapulmonary histoplasmosis). The low numbers of CD4+ CD29+
      memory cells, the high percentage of gamma delta T-cell receptor cells, and the
      recovery of CD4+ cells after treatment were remarkable.

PMID- 8877148
TI  - False-positive serologic test resulting from a probable yeast infection in a
      chimpanzee.
AB  - Sera used to identify putative hepatitis E viral proteins expressed in Pischia
      pastoris produced a false-positive reaction because of antibodies to a yeast
      protein. This report illustrates a potential problem when serological reagents
      are used in combination with recombinant proteins expressed in yeast.

PMID- 8877149
TI  - Selective gamma-chain T-cell receptor gene rearrangements in a patient with
      Omenn's syndrome: absence of V-II subgroup (V gamma 9) transcripts.
AB  - Only gamma-chain T-cell receptor transcripts utilizing V-1 subgroup gene segments
      were found in peripheral blood lymphocytes from a patient with Omenn's syndrome.
      gamma-Chain T-cell receptor transcripts utilizing the V gamma 9 (V-II subgroup)
      gene segment were absent in peripheral blood lymphocytes from this patient. V
      gamma 9 J gamma 1.2 C gamma 1 rearrangements are those primarily found in
      peripheral blood lymphocytes (70 to 85%) from normal donors.

PMID- 8877150
TI  - Evidence for and against chromosome 5q as a region of interest in asthma and
      atopy.

PMID- 8877151
TI  - The characterization of allergens.

PMID- 8877152
TI  - Signal transduction in eosinophils.

PMID- 8877153
TI  - Absence of linkage between 5q markers and serum IgE levels in four large atopic
      families.
AB  - BACKGROUND: Both genetic and environmental influences have been suggested to
      control the immunoglobulin (Ig)E response to allergens and, as a result, provide
      susceptibility to atopic disease. Two recent reports suggested that a major gene
      controlling basal IgE levels in humans was transmitted in a pattern consistent
      with autosomal recessive inheritance and was located on the long arm of
      chromosome 5 in the interleukin (IL)-4 gene complex. OBJECTIVE: The purpose of
      this report is to evaluate evidence for linkage of IgE with polymorphic genetic
      markers in the candidate region of 5q in four large pedigrees originally selected
      for studies of atopy. METHOD: Four large, highly characterized pedigrees in which
      IgE levels had been determined and genotypes at markers in the 5q candidate
      region were evaluated using both lod score and sib pair methods of analysis.
      RESULTS: In these pedigrees, we reject close to moderate linkage (up to 5 cM) of
      an IgE locus with markers on 5q. CONCLUSION: The genetic aspects of IgE
      regulation and its role in atopy remain controversial. The data suggest that
      should major genes be involved in the inheritance of atopy susceptibility, they
      are likely to be multiple in number and likely to involve interaction with other
      (exogenous) environmental exposures.

PMID- 8877154
TI  - Design of an optimally-diagnostic skin test solution for diagnosis of sensitivity
      to timothy grass (Phleum pratense) pollen.
AB  - BACKGROUND: Although most of the common allergen extracts that are used for
      diagnosis of type 1 hypersensitivity are now well standardized, this gives no
      assurance that they are within the concentration range that gives the best chance
      of a true diagnosis. OBJECTIVE: The objective of this study was to identify the
      most appropriate concentration range of timothy grass pollen Phleum pratense
      extract to diagnose sensitivity to this pollen correctly through skin-testing.
      METHODS: Dilutions of a well-standardized extract were made and used to skin test
      "true' positive and "true' negative populations of subjects as identified by case
      history, challenge tests and radioallergosorbent test (RAST). Weal diameters were
      measured and the data were submitted to receiver operating characteristics (ROC)
      analysis. For any particular weal size cut-off, the optimal diagnostic
      concentration (ODC) range was thus calculated. RESULTS: A 3 mm weal diameter cut
      off was chosen as an appropriate size for routine diagnosis. Therefore the ODC
      range at this diameter was used to establish a product target concentration and
      specification for formulation of the diagnostic reagent. This method of allergen
      extract standardization can lead to a true-biological unitage that can be used
      for labelling purposes. CONCLUSION: The optimum concentration range at which to
      formulate an allergen extract, in terms of an in vitro immunologically based
      assay, can be determined by carrying out ROC analysis of the results of clinical
      studies as described in this communication. Diagnostic units (DU), are now used
      by us for labelling of such final formulations which conveys the information that
      the product is at the most appropriate concentration for diagnosis.

PMID- 8877155
TI  - Relationship between nasal hyperreactivity, mediators and eosinophils in patients
      with perennial allergic rhinitis and controls.
AB  - BACKGROUND: In perennial allergic rhinitis, patients are almost daily exposed to
      aeroallergens. This ongoing allergic reaction results in increased sensitivity to
      allergens and non-specific stimuli. It is generally known that inflammatory cells
      and mediators are involved in the pathogenesis of the allergic reaction.
      OBJECTIVES: To study the relationship between nasal hyperreactivity and nasal
      inflammation during natural allergen exposure. METHODS: In 48 patients with
      perennial allergic rhinitis and in 11 volunteers a nasal brush, a nasal lavage
      and a histamine challenge were performed. Nasal inflammation was estimated by the
      number of eosinophils, levels of albumin, tryptase, prostaglandin D2 (PGD2),
      eosinophil cationic protein (ECP) and leukotriene C4/D4/E4 (LTC4/D4/E4). RESULTS:
      In contrast to PGD2 and tryptase, eosinophils (1.9 vs 0%, P = 0.0023), LTC4/
      D4/E4 (17.51 vs 1.43 pg/mL, P < 0.0001) and albumin (8.61 vs 2.37 mg/mL, P =
      0.0008) were significantly increased in rhinitis patients as compared with
      controls. Patients also showed increased responses to nasal histamine challenge
      assessed using a composite symptom score (21.5 vs 4 points, P < 0.0001). The
      nasal response to histamine was weakly correlated with the total number of
      eosinophils in the cytospin (correlation coefficient r = 0.38, P = 0.009).
      CONCLUSION: Nasal hyperreactivity is correlated with the percentage of
      eosinophils in patients with perennial rhinitis. The patients' mediator profiles
      suggest that eosinophils are important in the ongoing allergic reaction and nasal
      hyperreactivity.

PMID- 8877156
TI  - A comparison of the effects of oral cetirizine and inhaled beclomethasone on
      early and late asthmatic responses to allergen and the associated increase in
      airways hyperresponsiveness.
AB  - BACKGROUND: Cetirizine is a non-sedating H1 antihistamine which is effective in
      the treatment of allergic rhinitis and urticaria. It inhibits eosinophil and
      basophil chemotaxis in late cutaneous allergic reactions in skin windows. Its
      effect on early (EAR) and late asthmatic reactions (LAR) is less certain.
      METHODS: We examined the effect on EAR and LAR of 3 days treatment with oral
      cetirizine (15 mg twice daily) compared with a single dose of inhaled
      beclomethasone 10 min prior to allergen challenge in a placebo-controlled (oral
      and inhaled) double-blind cross-over design with three treatment arms separated
      by 14 days. RESULTS: Cetirizine did not significantly inhibit either the EAR or
      LAR documented by maximum percentage fall in FEV1 (0-3 and 6-9 h) or as area
      under the curve (AUC between 0 and 3 and 6-9 h). Beclomethasone inhibited the LAR
      compared with placebo (P = 0.02) when expressed as AUC (6-9 h). This did not
      quite reach statistical significance (P = 0.06) when expressed as maximal
      percentage late fall in FEV1 between 6 and 9 h. A greater than twofold increase
      in airways responsiveness to methacholine was observed 3 h after challenge which
      was significantly reduced by beclomethasone compared with placebo (P < 0.02) and
      cetirizine (P < 0.05). The data suggest that oral cetirizine does not
      significantly inhibit either the EAR or LAR. Beclomethasone inhibited both the
      early increase in airways responsiveness and the subsequent LAR. Our study also
      confirms the view that early increases in airway responsiveness precede the late
      response and suggests that these associated events are not dissociable by the
      pharmacological treatments employed in this study.

PMID- 8877157
TI  - Comparison of basophil histamine release, eosinophil cationic protein and non
      specific airway responsiveness between mite-sensitive asthmatic and non-asthmatic
      children and non-allergic controls.
AB  - To understand the relevance of allergy to the development of asthma in children,
      we examined basophil histamine release (HR) with Df antigen, blood eosinophil
      counts, serum eosinophil cationic protein (ECP) levels, and bronchial
      responsiveness to methacholine (PC20) in three groups of children, including 36
      asthmatics with high RAST titre for Df (group 1), 36 non-asthmatics with
      similarly high RAST titre for Df (group 2) and 21 non-asthmatics with negative
      RAST titre for Df (group 3). The amount of Df antigen inducing 50% HR from
      basophils did not vary significantly between group 1 and 2 (P > 0.05), while none
      of the cells responded to higher concentrations of Df in group 3. The mean number
      of blood eosinophils and level of serum ECP were highest in group 1, and lowest
      in group 3, with group 2 being intermediate, and the differences were significant
      between all three groups (P < 0.01). The mean PC20 value was the lowest in group
      1, intermediate in group 2, and the highest in group 3, and the differences were
      significant between all three groups (P < 0.01). While correlation studies showed
      that PC20 values of group 2 subjects significantly correlated with their
      eosinophil numbers (r = -0.48, P < 0.01) and ECP levels (r = -0.49, P < 0.01),
      such correlations were not found in group 1 subjects. These results suggest that
      the degree of the eosinophilic inflammation caused by the allergic reaction to
      mites is an important factor in determining the clinical expression of asthma in
      atopic subjects.

PMID- 8877158
TI  - Further characterization of histamine releasing chemokines present in
      fractionated supernatants derived from human mononuclear cells.
AB  - BACKGROUND: Histamine releasing factors (HRF) are members of the beta chemokine
      family of cytokines and have been characterized using recombinant proteins.
      Mononuclear cell and/or platelet supernatants have been shown to contain HRF and
      the initial void peak obtained using Mono Q anion exchange chromatography
      possesses such activity, as do two later peaks eluted from the column. OBJECTIVE:
      We wished to further characterize the activity present in the void peak and
      determine which of the chemokines present are responsible for the activity
      measured. METHODS: We fractionated the void peak obtained from Mono Q
      chromatography on Mono S. The elution profile of individual chemokines was
      determined and the fractions were assayed for histamine releasing capability. We
      used monospecific antisera to inhibit the activity and quantitate the
      contribution of each protein. RESULTS: The fractions contained MCP-1/MCAF,
      CTAPIII/NAP-2, IL8, and a small quantity of RANTES. About 90-95% of the total
      histamine containing capability was attributable to MCP-1/MCAF. There was a small
      contribution by CTAPIII/NAP-2, and RANTES, and no activity associated with IL8.
      CONCLUSION: MCP-1/MCAF is the critical HRF present in the initial void peak
      obtained by anion exchange chromatography of supernatants derived from human
      mononuclear cells and platelets. The alpha chemokine CTAPIII/NAP-2 has relatively
      weak activity and IL8 has none although they are prominent in this fraction and
      overlap with MCP-1/MCAF. RANTES makes a minor contribution but most of it is
      eluted in a later peak.

PMID- 8877159
TI  - Risk factors for latex allergy in patients with spina bifida.
AB  - OBJECTIVE AND METHODS: In order to study risk factors for latex allergy in
      patients with spina bifida, we investigated 165 patients with spina bifida (mean
      age 9 years). Besides answering a questionnaire, patients underwent skin-prick
      testing and determination of specific serum IgE to latex as well as a screening
      test for specific IgE to environmental allergens. A total of 80 patients (49%)
      were sensitized to latex according to the presence of specific IgE to latex.
      RESULTS: Skin-prick tests (SPT) with high ammonia latex milk were performed in 81
      of our patients with spina bifida and were positive in 36 patients (46%).
      Concordance of SPT with specific IgE in serum was good. Nineteen out of 165
      patients suffered from a clinically relevant latex allergy: five patients had a
      history of systemic reactions to latex (e.g. severe bronchospasm, anaphylactic
      reactions), mostly during surgery. Fourteen patients reported clinical symptoms
      while inflating a balloon; all these 19 patients were sensitized to latex. Number
      of operations ranged from one to 26 (mean 5 operations). Concentration of
      specific IgE to latex in serum correlated well with increasing numbers of
      operations. Some 32/76 patients (41%) with spina bifida who were sensitized to
      latex showed an atopic disposition, while 21 out of 81 latex-negative patients
      (26%) were atopic. Of 300 consecutive sera (mean age of patients 9 years) sent to
      our laboratory for routine determination of specific IgE, 144 (48%) were positive
      in terms of specific IgE to environmental allergens, of which 247144 (17%) were
      sensitized to latex. CONCLUSIONS: From our data we conclude that in order to
      minimize risk of severe systemic clinical reactions, all patients with spina
      bifida should be screened for their individual risk of latex allergy to plan
      preventive measures before operations. Main risk factors for latex allergy seem
      to be: more than five operations, atopic predisposition, history of clinical
      symptoms while inflating a balloon, and a sensitization with a CAP-class of > or
      = 4.

PMID- 8877160
TI  - Inhalative occupational and ingestive immediate-type allergy caused by chicory
      (Cichorium intybus).
AB  - We report a first case of occupational allergy to chicory (Cichorium intybus) in
      a vegetable wholesaler. Symptoms occurred after oral, cutaneous or inhalatory
      exposure. The patient also reported reactions after ingestion of botanically
      related endive (Cichorium endivia) and lettuce (Lactuca sativa). We identified
      the responsible allergen by SDS-PAGE and immunoblot to be a 48-kDa protein,
      confined to the non-illuminated parts of the plants. No cross-reactivity was
      found with mugwort (Artemisia vulgaris), ryegrass (Lolium perenne), and birch
      (Betula verrucosa) pollen, which suggests that the vegetable is the primary
      allergenic material.

PMID- 8877161
TI  - Mite control with low temperature washing. I. Elimination of living mites on
      carpet pieces.
AB  - BACKGROUND: Washing of delicate textiles at low temperature combined with mite
      control is one of the important aims for domestic mite prevention. OBJECTIVES:
      Estimation or assessment of mite numbers without and after the application of
      detergents or detergents with mite control additive. Trials at low temperature,
      detergents and washing as usual at household conditions (programme of a household
      washing machine). METHODS: The domestic mite Dermatophagoides farinae can be
      cultured on carpet samples under favourable conditions, and the breeding success
      monitored in terms of population and distribution using the free mite mobility
      test. The mite containing carpets were cut into pieces in order to investigate
      the effects of washing at low temperature with different commercial detergents
      with and without an additive for mite control. The heat escape method was used to
      assess the number of mites remaining on the carpet pieces. RESULTS: The
      estimation of the mite populations on different carpet pieces before and after
      washing showed that between 40 and 60% of the mites were able to resist washing,
      rinsing, spinning and drying. The allergen containing dust, however, was flushed
      out. In contrast, complete mite control was achieved by the application of the
      same detergents together with an additive. CONCLUSION: Mite control by low
      temperature washing is possible with a mite control additive provided that a
      concentration of benzyl benzoate of about 0.03% is achieved in the washing suds.

PMID- 8877162
TI  - Determination of the stability of diluted allergen extracts using a concentration
      step prior to EAST inhibition.
AB  - BACKGROUND: Generally the stability of diluted allergen extracts, as used for
      skin testing, provocation testing and immunotherapy can not be measured using a
      normal enzyme allergosorbent test (EAST) inhibition method. OBJECTIVE: The aim of
      this study was to determine the stability of diluted allergen extracts using an
      ultrafiltration step prior to the standard EAST inhibition procedure, in which
      the allergen extract was concentrated 100-fold. METHODS: This concentration
      procedure was validated for Dermatophagoides pteronyssinus, timothy pollen, birch
      pollen and cat dander extracts and used in a stability study in which three
      batches were stored for 1 year at 6 degrees C and 25 degrees C. RESULTS: There
      was no difference in relative potency before and after concentration of birch and
      timothy pollen extracts. D. pteronyssinus and cat dander extracts showed a
      significant decrease of 25% and 35% of the relative potency after concentration.
      The mean coefficient of variation of 12 determinations of the stability study was
      11.8%. CONCLUSION: For all allergens the 30 BU/mL or approximately 0.00025 mg/mL
      solution was stable for 12 months at both temperatures, except for D.
      pteronyssinus which declined rapidly at 25 degrees C.

PMID- 8877163
TI  - Airway hyperresponsiveness to acetylcholine induced by aerosolized arachidonic
      acid metabolites in guinea-pigs.
AB  - BACKGROUND AND OBJECTIVE: To investigate the role of arachidonic acid (AA)
      metabolites in airway hypersensitivity. METHOD: We studied the change in airway
      responsiveness to acetylcholine (ACh) after inhalation of some AA metabolites in
      guinea-pigs. RESULTS: Exposure to prostaglandin (PG) D2, thromboxane (TX) A2
      mimetic U-46619, leukotriene (LT) D4 or LTE4 at concentrations which did not
      influence bronchial tone and blood pressure dose-dependently caused airway
      hyperresponsiveness. However, the change was not observed after challenge with a
      high concentration of PGF2 alpha. Furthermore, PGD2 and U-46619 induced an acute
      and short-lived increase in responsiveness, while LTD4 and LTE4 induced a slow
      onset and longer-lived increase. In the tachyphylaxis study, although the
      tachyphylaxis for airway hyperresponsiveness provoked by PGD2 and U-46619 was not
      observed, airway hyperresponsiveness induced by the second LTD4 tended to
      decrease, and the second LTE4-induced airway hyperresponsiveness obviously
      diminished. In the study using antagonists and inhibitors, TX-receptor antagonist
      BM-13177 inhibited PGD2- and U-46619-, but not LTD4- and LTE4-induced airway
      hyperresponsiveness. TX synthase inhibitor OKY-046 had no effect on PGD2-, U
      46619- and LTD4-induced airway hyperresponsiveness, while LTE4-induced airway
      hyperresponsiveness tended to be inhibited by these inhibitors. However, the LT
      receptor antagonist ONO-1078 inhibited both LTD4- and LTE4-, but not PGD2- or U
      46619-induced airway hyperresponsiveness. 5-lipoxygenase inhibitor AA-861 tended
      to prevent LTE4-induced airway hyperresponsiveness, but had no effect on PGD2-, U
      46619- and LTD4-induced enhanced responses. CONCLUSION: These findings indicate
      that the local existence of PGD2, TXA2, LTD4 and LTE4 in the guinea-pig airway
      may act as an airway hyperresponsiveness-inducing factor rather than as a
      bronchoconstrictor. In addition, PGD2/U-46619 may stimulate the TX receptor to
      induce an acute and short-lived airway hyperresponsiveness, and LTD4 and LTE4,
      which may involve secondary mediator release, may act at the LT receptor to
      induce a slow-onset and longer-lived airway hyperresponsiveness, which may be
      associated with the induction, the development and the long duration of airway
      hyperreactivity.

PMID- 8877164
TI  - Rat basophil leukaemia (RBL) cells sensitized with low affinity IgE respond to
      high valency antigen.
AB  - BACKGROUND: The very low concentrations of IgE antibodies in serum make
      investigations of the affinity of allergen-specific antibodies extremely
      difficult. In the absence of such studies, the fact that low IgE concentrations
      are capable of inducing powerful effector function has encouraged the view that
      IgE antibodies are typically high affinity antibodies. Yet the phenomenon of
      allergic cross-reactivity suggests that lower affinity IgE antibodies may
      sometimes be of clinical significance. OBJECTIVES: To investigate the effect of
      antibody affinity upon mast cell sensitivity in an in vitro model. METHODS: Rat
      basophil leukaemia (RBL) cells were sensitized with one of three monoclonal IgE
      antibodies which bind to trinitrophenylated proteins with varying affinity.
      Serotonin release was measured after challenge of sensitized cells with
      trinitrophenylated human serum albumin (TNP-HSA). RESULTS: Low valency TNP3-HSA
      failed to stimulate degranulation of RBL cells sensitized with SPE-7 anti-DNP
      IgE, which binds TNP with low affinity. However, upon challenge with high
      concentrations (1250 ng/mL) of TNP8-HSA, or as little as 10 ng/mL of highly
      substituted TNP23-HSA, low levels of degranulation were seen. A similar
      relationship between antigen valency and cell sensitivity was seen with cells
      sensitized with the H-l epsilon-DNP anti-DNP IgE, which binds with moderate
      affinity to TNP proteins. CONCLUSION: High valency antigen is capable of
      activating RBL cells sensitized with low affinity antibody. This has important
      implications for our understanding of allergic sensitization. It also suggests
      that the long-recognized relationship between antigen valency and RBL cell
      sensitivity may partly reflect the high functional affinity of cell-bound IgE
      when directed against multivalent antigen.

PMID- 8877165
TI  - Inhibition of airways inflammation by dexamethasone is followed by reduced
      bronchial hyperreactivity in BP2 mice.
AB  - BACKGROUND: Infiltration of inflammatory cells in the airways is a constant
      characteristic of asthma and is considered to result in bronchial hyperreactivity
      (BHR). We have recently developed a model of BHR using a selection of mice, named
      BP2, which display eosinophil-dependent BHR following antigen challenges. An anti
      IL-5 antibody suppressed antigen-induced eosinophil recruitment to the airways
      and BHR in BP2 mice. OBJECTIVE: To investigate the implication of infiltrated
      inflammatory cells in the induction of BHR in mice. METHODS: The effects of
      glucocorticosteroid dexamethasone on airways eosinophilia and BHR were observed.
      RESULTS: Administration of dexamethasone at the dose of 1.25 mg/kg i.p. 1 h
      before each of four antigen provocations suppressed the airways eosinophilia and
      BHR in response to intravenous 5-HT and to aerosolized methacholine, as well as
      IL-5 production in the BALF and in the serum. By contrast, dexamethasone failed
      to reduce anaphylactic bronchoconstriction. CONCLUSIONS: These results suggest
      that dexamethasone exerts its inhibitory effects on antigen-induced airways
      eosinophilia in mice by inhibiting IL-5 production, but that it does not block
      the liberation of anaphylactic mediators in mice.

PMID- 8877166
TI  - Cerebral venous angiomas associated with hemorrhagic lesions. Their MRI
      manifestations.
AB  - Using two 1.5-T magnetic resonance (MR) scanners, 82 venous angiomas (VAs) were
      imaged. There were 13 (16%) VAs associated with hemorrhagic lesions. Ten of the
      13 hemorrhagic lesions were considered hematomas in the subacute or chronic
      stage, caused by VAs or coexisting cavernous hemangiomas. Two of the 13 were
      subacute intracerebral hematomas; the remaining one was a sequela of a
      hemorrhagic venous infarct. After analysis of our data, it was concluded that
      infratentorial VAs and deeply draining supratentorial VAs in relatively young
      adults, especially females, are relatively frequently associated with
      intracerebral hemorrhagic lesions. MR imaging proved useful for diagnosing VAs
      and associated hemorrhagic lesions.

PMID- 8877167
TI  - Fast inversion recovery for myelin suppression (FIRMS). A new MRI pulse sequence
      for highlighting cerebral gray matter.
AB  - The purpose of this study is to test a new pulse sequence, fast inversion
      recovery for myelin suppression (FIRMS) for its ability to improve the
      conspicuity of gray matter. Twenty-six seizure patients were scanned with FIRMS
      as well as standard sequences. Gray matter conspicuity was evaluated objectively
      using region-of-interest calculations, including image contrast, contrast ratios,
      and contrast:noise (C/N). In evaluation of the hippocampus and cortex, all
      objective measurements of conspicuity were highest for FIRMS. In five clinical
      cases of suspected cortical dysplasia, FIRMS improved delineation of pathology in
      positive cases and ruled out the diagnosis in negative cases. In a case of
      hippocampal sclerosis, FIRMS was able to demonstrate atrophy of the alveus. Fast
      inversion recovery for myelin suppression holds promise for its ability to
      highlight the cerebral cortex and hippocampus.

PMID- 8877168
TI  - MR imaging of multiple sclerosis simulating brain tumor.
AB  - Multiple sclerosis may sometimes present as a mass lesion that is
      indistinguishable from brain tumor both clinically and radiologically. We
      describe two cases of multiple sclerosis simulating brain tumor on computed
      tomography (CT) scans and magnetic resonance (MR) images, one of which was proved
      and another was suggestive to be demyelinating disease by biopsy. Steroid therapy
      produced regression of the lesions of MR images and CT scans. Our cases and
      others in the literature suggest strategies for detecting multiple sclerosis
      presenting as a mass lesion.

PMID- 8877169
TI  - Acquired intralobar bronchopulmonary sequestration secondary to occluding
      endobronchial carcinoid tumor.
AB  - We present the imaging findings of a 29-year-old man with an intralobar
      sequestration of the posterior segment of the left lower lung lobe, occurring
      distal to and sharing parasitized blood supply with a proximal occluding
      endobronchial carcinoid tumor. The etiology and pathogenesis of intralobar
      bronchopulmonary sequestration are discussed.

PMID- 8877170
TI  - Primary pulmonary chondrosarcoma mimicking bronchogenic cyst on CT and MRI.
AB  - Pulmonary chondrosarcoma is a rarely encountered primary tumor of the lung. We
      present a case with computed tomography and magnetic resonance imaging features
      mimicking a bronchogenic cyst.

PMID- 8877171
TI  - Detection of occult esophageal narrowing with a barium tablet during chest
      radiography.
AB  - Dysphagia is a delayed symptom of esophageal constriction and often appears after
      the luminal diameter is reduced to less than 10 mm. Earlier diagnosis of benign
      or malignant strictures while clinically silent would be desirable; hence we
      investigated the detectability of occult esophageal lesions with the aid of an
      ingested barium tablet during routine chest radiography. We prospectively
      examined 300 patients older than 40 years, who were referred for chest films
      because of indications unrelated to the upper gastrointestinal tract. Each
      patient was instructed to swallow a 12.5-mm barium tablet with 100 mL of water
      immediately prior to the exposure of posteroanterior and lateral chest films.
      Radiographs of 17 patients (5.6%) revealed intraesophageal retention of the
      tablet, and their prompt evaluation with double-contrast esophagrams confirmed
      various structural or functional abnormalities in 15 patients. Therefore, the
      oral administration of a barium tablet during routine chest radiography is a
      simple efficacious method to assess esophageal patency and detect occult
      narrowings from structural or functional causes.

PMID- 8877172
TI  - Inflammatory pseudotumor of the terminal ileum mimicking malignancy in a patient
      with Behcet's disease. CT and pathological findings.
AB  - Behcet's disease is an idiopathic, recurrent multisystem syndrome characterized
      by oral aphthous ulcers, genital ulcers, and ocular inflammation. Small bowel
      involvement may occur in 1% of patients with aphthous ulceration which may mimic
      Crohn's disease. We report a case of a patient with Behcet's disease with small
      bowel pathology which simulated a mass and at surgery was an inflammatory
      pseudotumor. Inflammatory pseudotumors can be mistaken for a malignancy as was
      the case in this patient.

PMID- 8877173
TI  - Intrauterine low density in women over 50. Assessment of significance and
      recommendations for follow-up.
AB  - Patients over 50 years old with intrauterine low density on enhanced computed
      tomography were analyzed. Uterine volume and volume of intrauterine low density
      were calculated. Intrauterine low density was expressed as a percent of uterine
      volume. At 1-year follow-up, 23 (63.9%) had uterine malignancy and 13 (36.2%) had
      benign findings. All patients whose intrauterine low density exceeded 35% of the
      total uterine volume had a malignancy (p < 0.001). If intrauterine low density
      exceeds 35% of uterine volume, evaluation of uterine malignancy should be
      performed regardless of symptoms.

PMID- 8877174
TI  - Color Doppler flow imaging of hepatocellular carcinomas. Comparison with
      metastatic tumors and hemangiomas by three-step grading for color hues.
AB  - The role of color Doppler imaging was evaluated in differentiating hepatocellular
      carcinomas (HCCs) from metastases and hemangiomas by the amount of tumoral color
      signals. Intratumoral and peritumoral color signals were analyzed by a three-step
      grading system (grade 1 to 3) in 51 patients (32 HCCs, seven metastases, and 12
      hemangiomas). Correlation of grading scores for intratumoral and peritumoral
      color signals was evaluated with the size of the tumors as well. HCCs
      demonstrated a higher grade of intratumoral color signals than did metastases or
      hemangiomas in all (p < 0.05) and biopsy-proved lesions (p = 0.0084); there was
      no significant difference in the degree of peritumoral color signals in all (p >
      0.05) or 17 biopsy-proved HCCs (p = 0.2078) from the other tumor groups. In
      addition, the grade of both intratumoral and peritumoral color signals was not
      related with the tumor size in all groups (p > 0.05). In conclusion, color
      Doppler imaging provided a valuable role in the diagnosis of HCCs based on the
      qualitative analysis of the intratumoral color signals.

PMID- 8877175
TI  - Magnetic resonance of the disk of the temporomandibular joint. MR imaging
      protocol.
AB  - Disk displacement can be well detected using proton density-weighted and T2*
      weighted two-dimensional gradient-echo sequences. In uncertain cases, especially
      if the bilaminar zone is not sufficiently represented, a contrast-enhanced T1
      weighted spin-echo sequence should also be performed. Also in patients with disk
      degeneration and osteoarthritis of the temporomandibular joint, proton density
      weighted and T2*-weighted two-dimensional gradient-echo sequences are of great
      diagnostic value. In this collective, however, T1-weighted contrast-enhanced spin
      echo sequences should be generally performed, to demonstrate inflammatory
      reaction of the synovia.

PMID- 8877176
TI  - Magnetic resonance imaging in pachydermoperiostosis.
AB  - Pachydermoperiostosis is a rare inherited disorder that is manifest clinically by
      digital clubbing, extremity enlargement, painful and swollen joints, hypertrophic
      skin changes, and periosteal bone formation. This report illustrates the skeletal
      findings that may be seen with long-standing disease as evaluated with
      conventional radiography and with magnetic resonance (MR) imaging, with emphasis
      on the MR appearance of periosteal reaction in this disorder. There are features
      that suggest pachydermoperiostosis may represent a generalized enthesopathy.

PMID- 8877177
TI  - MR demonstration of anomalous muscles about the volar aspect of the wrist and
      forearm.
AB  - Magnetic resonance (MR) examination of 42 normal wrists was performed for
      evaluation of anomalous musculature. A total of 23 muscle variations were found.
      An accessory abductor digiti minimi was found in 10 wrists (24%), an absent
      palmaris longus was found in seven wrists (16%), a muscular palmaris longus
      tendon was found in three wrists (7%), a muscular flexor digitorum superficialis
      was found in two wrists (5%), and an aberrant lumbrical muscle originating from
      within the carpal tunnel was found in one wrist (2.4%). Such muscle variations
      can be distinguished by MR from other mass lesions at the wrist and a knowledge
      of their frequency, appearance, and location can be of help in this regard.

PMID- 8877178
TI  - Trends in ENT training--a cause for concern.

PMID- 8877179
TI  - Cholesteatoma surgery today.
AB  - Four present-day surgical techniques are reviewed to assess their respective
      merits in surgery for cholesteatoma. The oldest method with an open cavity in
      ears with mastoid extension of cholesteatoma if combined with partial
      obliteration is still suitable for less experienced surgeons. Transcanal
      atticotympanotomy is suitable for limited epitympanic and tympanic cholesteatomas
      as long as it provides a direct view of the operative field. In similar ears,
      canal wall up surgery is employed if, additionally, mastoidectomy is needed
      because of chronic inflammation. Canal wall down surgery with full cavity
      obliteration with a musculoperiosteal flap, bone chips and bone pate should be
      the method of choice for all cholesteatomas extending beyond the facial nerve
      canal. The canal skin is kept as an intact tube and provides quick healing. Open
      cavities should be revised using similar obliteration techniques but, because of
      the lack of an intact canal skin tube, making use of a large modified Korner skin
      flap.

PMID- 8877180
TI  - Dehiscence of the greater palatine nerve. A risk factor in inferior turbinectomy?
AB  - Inferior turbinectomy, often combined with septal surgery, is frequently
      performed in the surgical treatment of nasal obstruction. A patient with post
      operative greater palatine anaesthesia occurring after this procedure prompted a
      study of the anatomy of the greater palatine nerve in the region of the inferior
      turbinate. Sixty-four lateral nasal walls were examined in cadavers. A dehiscence
      rate of 22% was noted, and in an additional 55% there was only a minimal bony
      covering to the nerve. Dehiscences occurred exclusively in the inferior meatus,
      anterior to the posterior bony end of the inferior turbinate. The narrow antero
      posterior extent of the dehiscence, the hard dense lateral nasal wall bone and
      the lateral position of the nerve in the canal help to protect the nerve from
      surgical trauma during turbinate surgery.

PMID- 8877181
TI  - Structure and origin of middle ear corpuscles.
AB  - The incidence, origin, structure and composition of middle ear corpuscles (MEC)
      were studied by dissection microscopy, by special stains and immunocytochemistry
      of histological sections and by transmission electron microscopy. MEC are formed
      within fibrous bands derived from transparent fibrous sheets which appear mainly
      in the mastoid antrum in the middle-aged and elderly. MEC are covered by a layer
      of epithelial cells with a normal basal lamina, and are largely composed of
      concentric layers of collagen which display alternating positive and negative
      birefringence. Pulmonary and prostatic corpora amylacea show a similar light
      microscopical structure and age relationship, but contain amyloid. It is
      suggested that MEC and the other bodies may be organized foci of epithelial
      basement membrane expansion perhaps derived from an in vivo counterpart of the
      "domes' seen in vitro in some monolayer epithelial cultures.

PMID- 8877182
TI  - Imaging of ear deformities in Treacher Collins syndrome.
AB  - Conductive deafness is a common feature of the Treacher Collins syndrome. The
      bilateral, essentially symmetrical hypoplastic deformities of middle and external
      ears, are characteristic. Improved imaging of the deformities using high
      resolution computed tomography (HRCT) has accompanied a present reluctance to
      explore surgically these middle ears because of poor results and the increasing
      success of bone anchored hearing aids. We describe the results of HRCT in 13
      patients with Treacher Collins syndrome. An unpneumatized mastoid and a greatly
      reduced attico-antral region are almost constant findings, but a proportion of
      patients have a patent external auditory meatus, and, only in these is
      exploratory surgery feasible. Correction of ossicular deformities may be
      possible. Patients with atresia of the external auditory meatus are not suitable
      for exploration and need bone anchored hearing aids. Imaging for these children
      should be limited with regard to radiation dose and sedation.

PMID- 8877183
TI  - The incidence and role of actinomyces in recurrent acute tonsillitis.
AB  - Although actinomyces has been identified in between 1.77% and 37% of resected
      tonsils its possible role in recurrent acute tonsillitis has received little
      attention. A histological and bacteriological study of 129 pairs of tonsils from
      patients with recurrent acute tonsillitis showed actinomyces to be present in
      29.5%. The organism, however, was also present in 40% of tonsils from 10 patients
      with no history of tonsillar disease. In neither of these groups was there any
      specific evidence of tissue reaction to actinomyces nor was there a male
      preponderance as in clinical actinomycosis. The presence of actinomyces in the
      tonsil was not favoured by the concurrence of beta-lactamase producing bacteria.
      These data indicate that actinomyces does not have a causal role in recurrent
      acute tonsillitis.

PMID- 8877184
TI  - Acoustic rhinometry in pre-school children.
AB  - Acoustic rhinometry was performed in 35 normal nose-breathing children between 3
      and 6 years. The average cross-sectional areas at the nasal valve, at the
      anterior end of the turbinates, and in the nasopharynx were 0.34 +/- 0.06 cm2,
      0.35 +/- 0.08 cm2 and 1.37 +/- 0.48 cm2 respectively. The average minimal cross
      sectional area was 0.29 +/- 0.06 cm2. The minimal cross-sectional area was
      located at the nasal valve in 14 and at the anterior end of nasal turbinates in
      21 of the 35 children. As would be expected, the cross-sectional areas at
      different sites of the nasal cavity increased with increasing age of the
      children. But, whereas the minimal cross-sectional area increased by 0.024 cm2
      per year, the nasopharyngeal cross-sectional area increased by 0.20 cm2 per year.
      No significant differences were found between boys and girls. Measurements of the
      posterior nasal and nasopharyngeal cross-sectional areas were unreliable,
      whenever the minimal cross-sectional area was less than 0.2 cm2. Furthermore,
      assessment of the nasopharynx may be difficult because of involuntary movements
      of the soft palate.

PMID- 8877185
TI  - Electromagnetic stimulation as a treatment of tinnitus: a pilot study.
AB  - This paper reports the results of a study to determine whether pulsed
      electromagnetic stimulation, applied over the mastoid bone, caused an improvement
      in the level of tinnitus in long-standing tinnitus sufferers. Fifty-eight
      patients from the Liverpool Tinnitus Association volunteered to take part in a
      double-blind placebo controlled trial. Active and placebo devices were randomly
      allocated to these patients on their first visit. At the end of one week of
      treatment, each patient noted whether their tinnitus had completely disappeared,
      was improved, unchanged or made worse by the treatment Forty-five per cent of the
      patients who completed the trial were improved by the active device, but only 9%
      by placebo (P = 0.0013, Mann-Whitney test). We suggest that electromagnetic
      stimulation may be an effective treatment in some tinnitus sufferers.

PMID- 8877186
TI  - Assessment of sequelae at home following adenotonsillectomy. A basis for day-case
      management?
AB  - Adenotonsillectomy is traditionally performed as an in-patient procedure.
      Although day-case adenotonsillectomy is practised in some units in the USA,
      Canada, Finland and Israel, it is rarely practised in the UK. This study looks at
      a cohort of 100 consecutive children admitted for adenotonsillectomy and follows
      their progress after discharge. It also assesses parental attitudes to day-case
      surgery. The results highlight parental anxiety associated with day-case
      adenotonsillectomy. Only 28% of parents would have liked the procedure to be
      carried out on a day-case basis with 46% of parents considering a single night
      stay to be too short. More support must be given to parents in the UK if day-case
      adenotonsillectomy is to become an acceptable procedure.

PMID- 8877187
TI  - Effect of topical beclomethasone on histamine-induced increases in nasal airflow
      resistance and secretion in perennial rhinitis.
AB  - The effects of topical beclomethasone dipropionate on changes in nasal resistance
      and secretion induced by topical histamine were studied in eight patients with
      perennial rhinitis. Patients were studied at enrollment, after 3 weeks of
      beclomethasone (100 micrograms spray to each nasal cavity twice daily), and after
      3 weeks of placebo (saline) treatment administered in a double-blind cross-over
      trial. Nasal airflow resistance (Rnaw) and total protein, albumin, lysozyme and
      glycoconjugate secretion in nasal lavage fluids were measured after topical
      application of histamine to the nasal mucosa. Resistance measurements and
      secretory parameters were similar for the initial study and after placebo
      treatment. In those studies, histamine (1 and 10 mg) increased both nasal
      resistance and secretion of total protein, albumin and glycoconjugates. After
      beclomethasone treatment the rise in respiratory resistance in response to
      histamine was significantly attenuated (delta Rnaw, +11.57 cm H2O/l/s with
      placebo, +5.80 with beclomethasone, P < 0.05). Beclomethasone had no effect on
      histamine-induced secretion. Because nasal resistance is determined mainly by
      vascular processes, beclomethasone treatment appears to have a prominent action
      on the vascular bed to reduce mediator-induced vasodilatation in perennial
      rhinitis.

PMID- 8877188
TI  - Tubomanometry. Values in ears with traumatic and chronic perforations.
AB  - The tubal function of 68 patients with a unilateral traumatic perforation of the
      tympanic membrane and 116 ears of 94 patients with chronic otitis media were
      examined by equalization manometry. The values obtained in the traumatic group
      are regarded as being characteristic of normal tubal function: the patients were
      able to equalize +/- 30 hPa difference in pressure with between three and seven
      swallows. Only 25% of the ears with a dry central perforation and none with an
      infected central perforation were able to fulfil this requirement.

PMID- 8877189
TI  - Tinnitus in pregnancy.
AB  - The presence of tinnitus in pregnancy was investigated by a postal questionnaire
      survey. A group of pregnant women attending the ante-natal clinic and a control
      group of non-pregnant members of the nursing staff at the Royal United Hospital
      in Bath were studied. The prevalence of tinnitus in the pregnant and non-pregnant
      women was compared. Both groups were similar in age, previous noise exposure and
      the presence of ear disease or operations. Twenty-five per cent of the pregnant
      women reported tinnitus compared with 11% of the control group. Chi-square
      analysis of this data gives a value of chi 2 = 4.07, d.f. = 1, P < 0.05. The
      result of our survey shows that there is significantly increased prevalence of
      tinnitus in pregnant women compared with a similar non-pregnant control group.
      This association has not been previously reported.

PMID- 8877190
TI  - The urban/rural divide in head and neck cancer--the effect of atmospheric
      pollution.
AB  - Inter-district variations in the incidence of head and neck squamous carcinoma in
      the period 1978-1987 have been identified from records at the West Midlands
      Cancer Registry, England. Analysis of the records reflect the national and
      international trend of higher urban cancer rates compared with neighbouring rural
      communities. Atmospheric pollution data (mean sulphur dioxide and smoke
      concentrations) from a national survey are positively correlated with squamous
      cancer of the larynx and pharynx. The correlation is most significant between
      laryngeal cancer rates and atmospheric sulphur dioxide levels. The periods 1950
      1970 and 1970-1990 have been analysed separately to reflect the reduction in
      atmospheric pollution that has occurred over these years and thus avoid missing a
      latent effect that this might have on cancer rates.

PMID- 8877191
TI  - The gag reflex and aspiration: a retrospective analysis of 120 patients assessed
      by videofluoroscopy.
AB  - An absent gag reflex is often employed clinically as an indicator of aspiration
      risk. Dysphagia clinic records of 120 neurological patients who had undergone
      speech therapy and ENT assessment, followed by videofluoroscopy, were
      retrospectively analysed to ascertain if any link between an absent gag reflex
      and aspiration could be demonstrated. No association between an absent gag reflex
      and aspiration or laryngeal overspill was found (Mann-Whitney U-test; 2-tailed P
      = 0.11). Abnormalities on indirect laryngoscopy were seen in 34/120 patients
      (28%), and these were more closely related to aspiration risk (Mann-Whitney U
      test: 2-tailed P = 0.06). An absent gag reflex is not a useful predictor of
      aspiration, and assessment of the gag reflex should not be relied upon to predict
      airway safety. However, indirect laryngoscopy is a useful adjunct to standard
      speech therapy assessment of the dysphagic patient.

PMID- 8877192
TI  - The relationship between middle ear pressure and deviated nasal septum.
AB  - The deviated nasal septum may be associated with middle ear problems,
      particularly on the side of nasal obstruction. This study aims to find out
      whether middle ear pressure (MEP) correlates with the degree of nasal obstruction
      secondary to a deviated nasal septum, and to examine changes in MEP following
      septal surgery. Patencies of the nasal passages (measured with a peak nasal
      inspiratory flowmeter) and MEP (measured with a tympanometer) of 55 patients were
      obtained prior to surgery and 7.5 (6-10) months post-operatively [median
      (range)]. Forty patients completed the study. Results were analysed by linear
      regression. In the ear on the side of nasal blockage, MEP was -25.7 +/- 28.4 mm
      water pre-operatively, and following surgery increased significantly to -2.9 +/-
      30.4 mm water (mean +/- SD) (P < 0.001). Pre-operatively, it was inversely
      related to the difference in patencies between the two nasal passages (r = -0.32,
      P < 0.02). Post-operatively, its improvement correlated with the degree of
      reduction of asymmetry of airway patency (r = 0.56, P < 0.001).

PMID- 8877193
TI  - Non-squamous malignancy in lymph nodes: the occult primary.
AB  - The present study presents 105 patients seen at a head and neck specialist clinic
      with a neck gland which subsequently proved to be a non-squamous malignancy. Of
      the 105 patients, 50 patients were eventually found to have a tumour in the head
      and neck region, 30 to have a distant primary and in 25 no primary site was ever
      found. The majority of patients were diagnosed in the clinic after careful
      examination and most of the remainder were diagnosed during endoscopy/biopsy.
      Chest radiography was the most useful investigation for diagnosing primary
      tumours of the lung. The 5-year-survival for the whole group of 105 patients was
      28% (95% CI 17-39). The 5-year-survival for the head and neck primary tumour
      group was 44% (95% CI 25-60). The median survival of patients with a distant
      primary tumour was only a 6 months, there was one 5-year-survivor. The median
      survival for those in whom the primary was never discovered was 18 months.
      However, a reasonable proportion of these patients survived, five being alive at
      5 years. The difference between survival for the three groups was statistically
      significant (P < 0.001). The most common histological type was
      undifferentiated/anaplastic tumours (37 out of 105) and this was followed by
      adenocarcinoma (33 out of 105). There was a significant difference in the
      survival between these two groups (chi 2 = 2.02, d.f. = 1, P = NS). Multi-variate
      analysis suggested that survival was better in the older age group and was
      affected by histology (P = 0.0093, P = 0.0332 respectively). The present study
      suggests that the treatment of patients in whom the primary site is eventually
      found to be in the head and neck region is rewarding with the same survival as a
      similar group of patients with squamous cell carcinoma. Sixty of the group of 105
      patients had excision biopsies of the neck node and this did not affect survival.

PMID- 8877194
TI  - Aural symptoms as primary presentation of Langerhan's cell histiocytosis.
AB  - Langerhan's cell histiocytosis is an uncommon granulomatous disease,
      characterized by the idiopathic proliferation of Langerhan's cells or their
      marrow precursors. It encompasses the diseases previously associated with
      histiocytosis X-eosinophilic granuloma, Hand-Schuller-Christian syndrome and
      Letterer-Siwe syndrome. A series of 54 patients were diagnosed with this
      condition in Dublin over a 33-year-period (1959-1992). Twenty-seven patients had
      aural symptoms, of whom 15 had no other lesions at the time of presentation.
      Otorrhoea was the most frequent otological symptom, followed by lesions in the
      temporal bone. LCH may mimic common aural conditions such as otitis externa,
      otitis media or acute mastoiditis and a high index of suspicion is required to
      recognize it on clinical presentation. The clinical presentation of multi-focal
      disease may be so dramatic that the otologic findings may be initially
      overlooked. The mortality rate was 14.8%. Therapeutic regimes included no
      treatment, curettage, chemotherapy, radiotherapy or multi-modality treatment.

PMID- 8877196
TI  - Dilation of the cochlear aqueduct--another otological myth?

PMID- 8877195
TI  - Retroviral p15E-related serum factors and recurrence of head and neck cancer.
AB  - Surgical removal of head and neck squamous cell carcinoma (HNSCC) restores the
      defective monocyte polarization found in patients with HNSCC. Since HNSCC contain
      p15E-like low molecular weight factors < 25 kD (LMWF) capable of suppressing N
      formyl-methionyl-leucylphenylalanine (fMLP)-induced monocyte polarization, it is
      likely that HNSCC removal eradicates the production site of p15E-like factors.
      This report describes a prospective follow-up study on the levels of bioactive
      p15E-like serum factors for a period of 2 years in nine patients with HNSCC who
      had no recurrence and 11 patients with HNSCC who showed residual or recurrent
      disease after treatment. In the group of patients without recurrent disease p15E
      like bioactivity gradually decreased and eventually became negative. In patients
      with recurrent/residual disease p15E-like bioactivity remained high or even
      became positive before or at the time of diagnosing tumour recurrence. This study
      strongly supports the concept that HNSCC tumours are the production site of p15E
      like immuno-suppressive factors and indicates that serum p15E-like factors may be
      used for future studies on early serum markers for recurrent/residual disease
      developing in the first year after treatment.

PMID- 8877197
TI  - Tympanosclerosis.

PMID- 8877198
TI  - Computerized tomography of acute, tender peritonsillar swellings.
AB  - A randomized trial involving 40 consecutive patients with an acute painful
      peritonsillar swelling was set up to determine if an enhanced computerized neck
      tomogram was cost-effective or improved patient management. Each patient was
      placed into one of two groups. The first group had enhanced computerized
      tomography (CT) which allowed precise identification of a quinsy and this was
      aspirated with an 18G needle aspiration at the site directed by the scan. The
      second group of patients had 3-point permucosal 18G needle aspirations. A
      proportion of patients from each group, but primarily from the second, required
      immediate or delayed admission to hospital after aspiration, for persistent or
      recurrent symptoms. Costing each groups treatment, including the scan and
      hospitalization on intravenous antibiotics, we conclude that CT scanning prevents
      the morbidity associated with unsuccessful attempts at drainage in the patient
      with cellulitis and ensures complete drainage of pus, thereby optimizing patient
      treatment and it is cost-effective.

PMID- 8877199
TI  - Doppler ultrasonography as a pre-operative aid to base the forearm flap on the
      radial or ulnar artery.
AB  - The elevation of a forearm flap based on the ulnar artery has been described as
      an alternative to a flap based on the radial artery. Despite the fact that 15-30%
      of operated patients complain of symptoms in the hand due to impaired
      circulation, this flap is still regularly raised upon the radial artery. Using
      Doppler ultrasonographic examination before elevating the forearm flap, the
      dominant artery to the hand can be determined. The preliminary experience in 11
      patients operated upon (the flap has been based upon the ulnar artery five times)
      is satisfactory. None complained of weakness of the hand, a feeling of coldness
      or cold intolerance.

PMID- 8877200
TI  - Vocal rehabilitation after total laryngectomy using the Provox voice prosthesis.
AB  - Vocal rehabilitation in laryngectomized patients can be attained by surgical
      (tracheoesophageal speech) or conservative methods (oesophageal speech or
      artificial larynx). We prospectively studied voice restoration in 37 patients who
      underwent total laryngectomy in the period from February 1991 to February 1993.
      The patients were given the opportunity to assess both non-shunt oesophageal
      speech and shunt oesophageal speech using the Provox voice prosthesis. The Provox
      low resistance, self-retaining voice prosthesis is a biflanged device made of
      silicon rubber. A primary tracheoesophageal puncture was made in 28 patients,
      while a secondary puncture was performed in another nine patients. The results
      were assessed according to criteria established at the 'Third International
      Congress on Voice Prosthesis' in Groningen (1988). Functional tracheoesophageal
      speech after primary puncture was achieved in 95% of patients 12 months after
      puncture, while oesophageal voice was acquired by 55%. Only minor surgical and
      prosthesis-related complications were encountered during this follow-up period in
      29% of the patients. The device lifetime varied from 3 months to at least 2 years
      (mean 5.4 months).

PMID- 8877201
TI  - Bilateral acoustic neuromas.
AB  - This article reviews 12 patients with bilateral acoustic neuromas. The sex
      incidence was equal and the mean age at diagnosis was 26.2 years. The family
      history was positive in nine of the patients. Five patients have had incomplete
      surgical removal of acoustic neuromas on both sides. Two of them are completely
      deaf and the other three have severe sensorineural hearing loss in one ear and no
      hearing in the other ear. In five patients the tumour on one side has been
      operated on and the other side is being observed with at least short-term
      preservation of good hearing. The remaining two patients died of intra-cranial
      complications, one of them post-operatively. Four patients developed facial palsy
      immediately following surgery and one developed facial weakness 6 months after
      surgery. Guidelines are discussed for the care of these patients including the
      timing of surgery and alternative treatment options (observation, radio-surgery
      and chemotherapy). This is essentially a group of young individuals who have had
      multiple operations for bilateral acoustic tumours and associated manifestations
      and for whom the disease and the sequelae of treatment can be tragic.

PMID- 8877202
TI  - Out-patient management by junior staff: the value of consultant supervision.
AB  - The effect of consultant supervision on management of patients by junior staff
      was assessed. Supervision was exercised by pre-reading the notes with the
      consultant at the start of the clinic. The principle finding was that less
      patients were brought back for another appointment. For new patients, the
      proportion fell from 40% to 19%, and for follow-up patients it fell from 49.5% to
      29%. The overall rate fell from 46% to 23.5%. This has major implications with
      respect to use of resources and, in the unit studied, this change would make
      available 38 extra clinic appointments for each registrar per month. The study
      also raises issues regarding the use of out-patient clinics for post-graduate
      training and consultant supervision of patient management in general.

PMID- 8877203
TI  - Natural frequencies of vibration of a fibre supported human tympanic membrane
      analysed by the finite element method.
AB  - A finite element programme developed previously to calculate the natural
      frequencies of vibration of the human tympanic membrane, has been modified to
      take into account both natural and geometric rigidities. The natural rigidities
      take the form of internal membrane stress/strain parameters, while the geometric
      rigidities are the flexural and membrane stress resultants. The first six natural
      frequencies calculated are similar to those measured by Laser holography on
      cadaver membranes and analysed recently by interference techniques. Using a
      generalized stress/strain constitutional relationship, the natural frequencies
      were found to be linearly related to the square root of the forces within the
      membrane. It was proposed in our earlier work, that these internal stresses as
      well as maintaining the complex shape of the tympanic membrane, serve to enhance
      its frequency range and response. The role of the radial and circular fibres
      embedded within the ground substance of the membrane on the frequencies and mode
      shapes have also been examined by super-imposing beam elements on the semi-loof
      membrane elements. It was found that the modes of vibration of the membrane are
      restricted to a fairly simple pattern up to beam moduli values of approximately
      50 MPa. Above this beam modulus, the normal mode shape was observed with a
      gradually increasing complex vibration pattern as the frequency increases. This
      new treatment of membrane re-enforcement suggests a non-Hookean behaviour of the
      drum displacements. In order to account for the earlier measured frequencies of
      Tonndorf & Khanna, the previously proposed internal stress/strain parameters are
      believed to be less important and have been calculated to be small compared with
      the membrane modulus.

PMID- 8877204
TI  - The vascular supply of the lenticular and long processes of the incus.
AB  - Previous reports of the blood supply to the lenticular and long processes of the
      incus have failed to consider the potential contribution of the periosteal
      vascular plexus. This scanning electron microscopic study of vascular foramina on
      the cortical bone surface demonstrates that there is no statistical difference
      between the numbers of vascular foramina on the lenticular and long processes, as
      opposed to the body and short process. These results suggest that the blood
      supply to this portion of the ossicular chain may not be as tenuous as has been
      thought.

PMID- 8877205
TI  - Speech changes following uvulopalatopharyngoplasty.
AB  - Velopharyngeal function, voice and speech changes following
      uvulopalatopharyngoplasty (UPPP) were studied prospectively and compared with
      those in an age and sex matched group undergoing tonsillectomy. The fundamental
      frequency of voice was significantly lower in those undergoing UPPP. All the
      other changes studied were not significantly different in the two groups.

PMID- 8877206
TI  - Current practice of stapedectomy in Great Britain.
AB  - Since the introduction of stapedectomy with reconstruction of the ossicular chain
      to Great Britain, many modifications in practice have taken place. The changes
      include patient selection, operative technique and the type of prosthesis used,
      as well as the number of operations performed yearly. The aim of this study is to
      attempt to establish the actual practice among British otolaryngology consultants
      by means of a simple questionnaire. Two hundred (50.3%) forms were analysed
      anonymously. The study confirms the decrease in the number of operations
      performed annually, the absence of centralization for this type of surgery in
      Great Britain and also demonstrated the trends towards stapedotomy and the
      practice of bilateral surgery amongst younger consultants.

PMID- 8877207
TI  - Does the type of middle ear aspirate have any prognostic significance in otitis
      media with effusion in children?
AB  - Two hundred and twenty-two children with chronic, bilateral middle ear effusions
      were assessed during a 2 year follow-up period. At initial myringotomy the middle
      ear aspirate was found to be serous in 44 children and mucoid in 178 children.
      Evaluation at 1 and 2 years post-operatively showed no difference in otoscopic
      fluid clearance or mean hearing threshold at either follow-up time in relation to
      either type of fluid. There was no greater need for ventilation tube reinsertion
      in either group during the overall follow-up period. There was found to be no
      significant difference between the children with serous or mucoid effusions in
      relation to a range of pre-operative and operative variables. The study suggests
      that outcome in terms of fluid clearance and hearing thresholds is independent of
      the fluid type and there appears no greater need for revision ventilation tube
      insertion in relation to the findings at myringotomy. The type of effusion found
      on aspiration prior to ventilation tube insertion has no prognostic value.
      Children with serous fluid should be managed in an identical manner to those in
      which the fluid is thicker and mucoid in character.

PMID- 8877208
TI  - The effect of N-acetylcysteine on the in vitro growth of normal rabbit middle ear
      fibroblasts.
AB  - In the present study the effect of N-acetylcysteine on the growth pattern and
      collagen synthesis of cultures of rabbit middle ear fibroblasts was determined.
      The growth pattern was evaluated by cell counting, measurements of the total
      content of cell protein and mitotic activity by incorporation of 3H-thymidine.
      Collagen synthesis was estimated by incorporation of 3H-proline. The results
      demonstrate a dose-dependent reduction in both normal cell proliferation and
      collagen production. Thus, N-acetylcysteine seems to possess properties desirable
      and useful in the treatment of secretory otitis media.

PMID- 8877209
TI  - Day-case adenoidectomy--is it safe?
AB  - A controlled prospective study was performed on 429 consecutive children
      undergoing adenoidectomy, of which 263 were day-cases. Adenoidectomy was done
      alone, or in combination with other minor procedures. There was only one
      reactionary haemorrhage in each group, and these were early and easily recognized
      by the recovery staff. No other significant complication was seen. Adenoidectomy
      in children as a day-case procedure is safe and cost-effective.

PMID- 8877210
TI  - Lens tube vs Donaldson tube: results of a prospective study comparing a new with
      a conventional ventilation tube.
AB  - A prospective study was undertaken in 72 children comparing a new type of
      tympanostomy tube, the Lens tube, in one ear, and a Donaldson tube in the contra
      lateral ear as a control. The average survival times of the tubes differed
      significantly: 17.20 months for the Lens tube, and 11.31 months for the Donaldson
      tube (P < 0.001). By contrast, the relapse rate (22% with the Lens tube vs 21%
      with the Donaldson tube) after extrusion or extraction, and the residual
      perforation rate (3% with the Lens tube vs 6% with the Donaldson tube) were not
      significantly different. Otorrhea was not significantly different either: 25%
      with the Lens tube vs 16% with the Donaldson tube.

PMID- 8877211
TI  - Pre-admission assessment clinics: an answer to non-attendance for ENT operations.
AB  - Non-attendance by patients for elective surgery with insufficient time to find
      replacement leads to wasted theatre time and wasted resources. The introduction
      of pre-admission clinics at the North Riding Infirmary, Middlesbrough has
      alleviated this problem and has led to considerable financial savings. A 12 month
      prospective study has shown an increase in operations performed from 3738 to
      3944. Financial savings have not been taken into consideration in this
      publication.

PMID- 8877212
TI  - Peripheral facial palsy: antibody levels to Borrelia in serum and CSF.
AB  - Serum antibodies to Borrelia burgdorferi antigen were determined in 71
      consecutive patients with an acute peripheral facial palsy. The study was
      conducted for one year in a south western coastal region in Sweden. Twenty-one
      per cent of the patients had significantly elevated serum levels of antibodies to
      Borrelia burgdorferi antigen. CSF was examined in 13 of the sero-positive
      patients. In three of these (23%) Borrelia antibodies were found. Another five
      patients had a pathological protein and cell pattern in the CSF. No seasonal
      differences were observed. Four of the sero-positive patients had a long-term
      history of dermatological neurological manifestations compatible with the late
      third stage of the disease.

PMID- 8877213
TI  - Acoustic rhinometry: validation of volume changes following intra-nasal
      polypectomy.
AB  - Acoustic rhinometry measures nasal cavity geometry by analysis of reflected
      acoustic impulses. Previously, the technique has been applied to normals,
      patients with septal deviations and rhinitis and to monitor the medical treatment
      of nasal polyps. To date, no study has been published to validate the application
      of this technique where nasal polyps are present. In this study, acoustic
      rhinometry has been used to assess the change in nasal cavity volume following
      intra-nasal polypectomy in 20 subjects. The volumes of the polyps removed
      surgically were measured by displacement and compared with the volume change
      recorded by acoustic rhinometry. A correlation of r = 0.59 (P = < 0.01) has been
      obtained. Therefore, it is possible to apply acoustic rhinometry as a method of
      assessing non-surgical treatment of nasal polyps given certain conditions.

PMID- 8877214
TI  - Throat pain and pharyngeal packing: a controlled randomized double-blind
      comparison between gauze and tampons.
AB  - In order to determine whether patients having pharyngeal packing experience more
      or less post-operative throat pain when tampons were used, 80 patients were
      randomized into two groups to receive either gauze or tampon pharyngeal packing.
      A third control group of 40 patients were intubated but did not have any throat
      packs. Post-operative throat pain was subjectively rated at both 6 hours and at
      24 hours by an independent observer. Thirty-eight per cent of patients had
      moderate or severe throat pain in the gauze group, whilst in the tampon and
      control groups these amounted to only 15% and 1% respectively. A significantly
      higher proportion of patients also had a moderate or severe sore throat at 24
      hours in the former group. Intubation alone resulted in a sore throat post
      operatively in 50% of patients, but 85% of those had a mild sore throat only. No
      differences in pain ratings in any group could be shown between men or women or
      between age groupings. Endotracheal intubation often causes post-operative throat
      pain which is exacerbated by the use of pharyngeal packing. The results presented
      suggest that tampons are a safe, effective alternative to gauze and result in
      less severe post-operative throat pain.

PMID- 8877215
TI  - Sex and grommet operations.
AB  - Sex differences in patients having grommet operations in Scotland were analysed
      to provide further evidence on whether girls should be managed differently from
      boys. In children treated at less than one year, 64% were boys, but this
      proportion declined with age and, after the age of 13 years, became less than
      50%. The median age at treatment and the repeat operation rate were similar for
      both sexes. Different management according to the sex of the patient does
      therefore not appear to be justified.

PMID- 8877216
TI  - Peri-umbilical superficial fascial graft myringoplasty--a simple alternative.
AB  - We present new material in the surgical repair of the perforated tympanic
      membrane. Forty-two patients with a unilateral tympanic membrane perforation and
      eight patients with bilateral perforations had their perforations closed with
      peri-umbilical superficial fascia via a transtympanic route. Of the 58 tympanic
      membranes repaired, 51 were successful while seven failed. The technique is cost
      effective and quick, making bilateral repairs possible under the same
      anaesthetic.

PMID- 8877217
TI  - The clinically N(0) neck: investigation and treatment.

PMID- 8877218
TI  - Cartilage grafts for the nasal tip.
AB  - Control over nasal tip projection is essential in rhinoplasty. Nasal projection
      is defined as the length of the perpendicular drawn from the anterior facial
      plane to the tip-defining point. The nasal lobule shield-type graft, made of
      autologous cartilage, is one of the most important methods to maintain
      projection. The graft may also control length, (counter)rotation of the nose and
      refinement of the tip. The external approach facilitates in-situ suturing and
      sculpting of the graft. Between 1989 and 1991, 300 patients underwent an external
      rhinoplasty. In 94 (31%) an autologous graft for the nasal tip was used. The
      aesthetic result was pleasing to the vast majority of the patients. Nasal tip
      rigidity resolved in all patients within one year post-operatively. One patient
      needed revision surgery, because of graft resorption.

PMID- 8877219
TI  - The effects of grommet insertion on Eustachian tube function.
AB  - A prospective study on the effect of grommet insertion on the passive Eustachian
      tube opening pressure was undertaken in children's ears with otitis media with
      effusion. After an initial immediate improvement following aspiration of the
      middle ear no further change in Eustachian tube function occurred over 4
      subsequent weeks. Grommet insertion probably has no effect on Eustachian tube
      function.

PMID- 8877220
TI  - Value of computed tomography (CT) in the diagnosis of cochlear otosclerosis.
AB  - The temporal bones of 40 patients with surgically confirmed otosclerosis were
      studied with high-resolution CT. The hearing of these patients was re-examined 5
      years later. Foci of demineralization in the cochlear capsule were detected in
      36% of operated ears and in 44% of otosclerotic ears not operated on. Mean bone
      conduction (BC) thresholds of ears with positive radiological findings did not
      differ significantly from those of otosclerotic ears with normal CT, either at
      the time of CT examination or 5 years later. Over 5 years, elevation of BC
      thresholds by 10 dB or more was observed significantly more often in operated
      ears with abnormal CT than in operated ears with normal CT, but in otosclerotic
      ears not operated on the corresponding difference was non-significant. It was
      concluded that CT examination is of little value in predicting sensorineural
      hearing loss in patients with otosclerosis.

PMID- 8877221
TI  - Hearing protection for motorcyclists.
AB  - An investigation to ascertain the most suitable earplug and its efficacy for use
      by motorcyclists was undertaken. To qualify for testing the earplugs had to be
      both easily available and cost less than 10 Pounds. Consequently, three types of
      earplugs ('Silisoft', EARfit and AQUAfit [both Cabot Safety Ltd]) were tested for
      sound attenuation scores using an 'insertion loss' technique both with and
      without a motorcycle helmet and scored for comfort by the test subjects. The
      optimal plug was then assessed as to its effect on the temporary threshold shift
      occurring in motorcyclists after prolonged high speed riding. There were no
      significant differences between the sound attenuation scores of the three plugs
      tested, with all three earplugs providing approximately 15 dB of sound
      attenuation at the low frequencies (250, 500, 1000 Hz) when worn under a helmet.
      The soft yellow foam earplug was felt to be the optimal plug for motorcyclists as
      it was significantly more comfortable (Wilcoxon paired: P < 0.01), readily
      available (chi 2 = 15.2, P < 0.001) and the cheapest. After one hour of high
      speed riding (80 mph), riders suffered a mean maximal temporary threshold shift
      of 11 dB at 1000 Hz which was abolished by wearing these earplugs. Earplugs
      appear to provide useful protection against the excessive noise levels
      experienced by motorcyclists. The soft yellow foam plug (EARfit, Cabot Safety
      Ltd) would appear to be the most suitable, on the grounds of its low cost,
      comfort and ease of availability.

PMID- 8877222
TI  - Human papillomavirus in laryngeal papillomas and in adjacent normal epithelium.
AB  - Eleven adults with laryngeal papillomas were studied for the presence of human
      papillomavirus (HPV) DNA by in situ hybridization. As well as from the
      papillomas, three additional biopsies were taken from the normal-appearing mucosa
      as follows: the involved vocal cord, the opposite vocal cord (when the papilloma
      was unilateral), and from the ventricular fold on the side of the lesion. These
      normal tissues were analysed by polymerase chain reaction (PCR) to detect HPV
      DNA. All except one of the 11 papillomas contained HPV DNA; nine were HPV 6/11
      DNA positive and one positive for HPV 16 DNA. The normal-appearing laryngeal
      mucosa harboured HPV DNA in eight out of 11 patients. The present results
      strongly support the concept that the adult-type laryngeal papilloma is an HPV
      induced lesion, mostly due to HPV types 6 and 11. The persistence of HPV DNA in
      the adjacent normal epithelium is consistent with the frequent recurrence of
      these lesions.

PMID- 8877223
TI  - Paediatric cochlear implantation: how reliable is computed tomography in
      assessing cochlear patency?
AB  - This study investigates the accuracy of pre-operative high resolution computed
      tomographic (CT) scans in predicting the patency of the cochlea in children
      undergoing cochlear implantation. The first 26 children on the Nottingham
      Paediatric Cochlear Implant Programme were reviewed. CT scans were performed
      utilizing 1 mm contiguous sections and these were then assessed by a
      neuroradiologist. In patients who had normal inner ears on CT a high degree of
      accuracy in predicting a patent cochlear was achieved (87%). However, in 15% of
      cases the degree of ossification was significantly under-estimated causing major
      difficulties at the time of surgery. Although high resolution CT offers great
      clarity and fine detail, it has its limitations. Further information may be
      provided by magnetic resonance imaging.

PMID- 8877224
TI  - A grading system for patients with obstructive sleep apnoea--based on sleep
      nasendoscopy.
AB  - One of the most important parts of the management of patients with the
      obstructive sleep apnoea syndrome is the assessment of the level of obstruction
      in order to allow the appropriate choice of treatment. We have recently developed
      the technique of sleep nasendoscopy which allows direct visualization of the site
      of obstruction in the sleeping patient. Having performed over a hundred of these
      investigations we are able to suggest a grading system for these patients
      dividing them into five grades. Grade 1 = simple palatal level snoring; grade 2 =
      single palatal level obstruction; grade 3 = palatal level obstruction with
      intermittent orohypopharyngeal involvement; grade 4 = sustained multi-segment
      involvement; grade 5 = tongue-base level obstruction. We feel that this grading
      system will help in deciding which patients are suitable for surgery and which
      are not; hence avoiding unnecessary operations and allowing a more logical
      decision on the appropriate form of treatment. Results of the first 90 patients
      to have sleep nasendoscopy are presented.

PMID- 8877225
TI  - Is there a relationship between the degree of nasal obstruction and snoring?
AB  - The possible connection between snoring and nasal obstruction was studied in
      three groups of adult patients. In group 1, comprising 112 unselected patients,
      36% snored, and 50% of the snorers suffered from nasal obstruction. The other two
      groups consisted of selected patients: group 2 (n = 41) and group 3 (n = 40) all
      of whom suffered from nasal obstruction. In group 2 nasal airway resistance was
      normal both before and after decongestant treatment, and in group 3 nasal airway
      resistance was pathologically high even after decongestant treatment. No
      difference was found between groups 2 and 3 regarding snoring. Sixty-six per cent
      in group 2 and 78% in group 3 snored. There was a correlation between snoring and
      the subjective nasal obstruction, but none between snoring and the degree of
      nasal obstruction expressed as nasal airway resistance.

PMID- 8877226
TI  - A longitudinal pilot study on phonetograms/voice profiles in pre-pubertal choir
      boys.
AB  - The phonetogram or voice profile, measuring frequency combined with intensity of
      the voice, has replaced simple measurement of tone ranges for analysis of
      professional boys choirs. Knowledge of the relationship between pubertal, sex
      hormones, and phonetogram development has been established in stratified studies.
      The connection between the singing voice in puberty and other pubertal phenomena
      needs documentation in longitudinal studies also. Therefore, a pilot study was
      carried out, where three boys aged 13-15 years were analysed at intervals of 2
      months. Measurement of phonetograms, free and total serum testosterone and sex
      hormone binding globulin (SHBG) showed a significant relationship between SHBG
      and lowering of the lowest tones in the phonetograms (P < 0.01) confirming
      earlier stratified studies.

PMID- 8877227
TI  - The use of the rat facial nerve model to assess the effect of differing nerve
      anastomotic agents on the facial nerve.
AB  - There are relatively few papers which prove that one nerve anastomotic agent for
      the facial nerve is superior to any other. Previous experiments on the division
      and anastomosis of the facial nerve have failed to consider the indeterminate
      variables involved, i.e. operator variability, controls and the reaction of the
      materials on normal nerve tissue. In this experiment, a variety of anastomotic
      agents were tested to see if the anastomotic agents themselves affected the extra
      temporal facial nerve function. The absorbable suture, non-absorbable suture,
      glue and tube wrap used had no effect on normal nerve tissue or on the
      anastomosis of the sectioned facial nerve of the rat compared with simple laying
      together of the divided ends of the divided nerve.

PMID- 8877228
TI  - Otorrhoea via ventilation tubes in adults and children.
AB  - A prospective investigation of 127 children and 41 adults undergoing ventilation
      tube (grommet) insertion has been carried out. One or more episodes of discharge
      via a ventilation tube occurred in 14% of the children and 27% of the adults
      during the in situ lifetime of the tube. So far, 44 of the children have
      undergone insertion of a second ventilation tube, and of these, 7% have had
      discharge from one or both tubes. In the paediatric group, discharge was more
      likely if the child had a history of atopy (Chi-squared, P < 0.03, multiple
      regression P < 0.03). No other risk factors were identified, but two patients
      with cholesteatoma were identified in the group with discharge via a tube. In
      patients with otorrhoea via a tube, which does not settle after removal of the
      tube, mastoid exploration should be considered.

PMID- 8877229
TI  - An assessment of the reproducibility of combined glottography in a clinical
      setting.
AB  - Although combined glottography has potential as a clinical tool, it has had
      limited use in the monitoring of laryngeal function before and after treatment.
      There is no data about the standardization nor reproducibility of the procedure.
      An indication of the reproducibility of combined glottography is paramount if
      changes in laryngeal function are to be measured accurately. Using a standardized
      technique, two complimentary studies examined the reproducibility of combined
      glottography within one sitting (Study 1) and over time (Study 2). The components
      of variance were analysed (ANOVA). In Study 1 the variance under controlled
      conditions for Open Quotient (OQ) and Speed Quotient (SQ) was only 13% and 18%
      respectively of the total, whilst in Study 2 the variance over time for OQ and SQ
      was 55% and 58% respectively. Under controlled conditions combined glottography
      is a reproducible technique.

PMID- 8877230
TI  - A comparison of combined glottography in men and women.
AB  - Out-patient combined glottography has shown potential in the assessment of the
      vocal cord cycle in laryngeal abnormality. We compared this technique in men and
      women with normal laryngeal function, to evaluate the influence of patient sex on
      the results. Ten adult men were compared with 10 age matched women. The open
      quotient was significantly greater in women. This indicates the woman's glottis
      is open for a greater proportion of the glottic cycle, as a result of the
      anatomical and physiological differences of the larynx between the sexes.
      Analyses are made of the glottic cycle differences which may account, in part,
      for the different quality of the female voice. Interpretation of results using
      this technique must take account of the patient's sex.

PMID- 8877231
TI  - Hypochondriasis in ENT practice.
AB  - In this study the incidence of hypochondriasis among new ENT out-patients was
      investigated. A validated questionnaire, which was administered twice with an
      interval of 3 months, was used to make the diagnosis. Medical information also
      played a part in the assessment. The diagnosis hypochondriasis applied to 13% of
      the patients who completed the entire diagnostic procedure. This group made very
      frequent use of a range of medical services and took a large amount of medicine.
      Compared with the non-hypochondriacal ENT group, the hypochondriacal group had a
      more negative opinion about their own health, although those in the latter group
      were less ill, measured by objective criteria. In order to be able to diagnose
      hypochondriasis in ENT practice, psychological or psychiatrical consultation is
      necessary.

PMID- 8877232
TI  - Effect of pre-operative antibiotic treatment on the bacterial content of the
      tonsil.
AB  - The impact of 7 days pre-tonsillectomy antibiotics on the aerobic bacterial
      content of the tonsil was studied in 70 consecutive patients. One group received
      no antibiotic, one group received pre-operative amoxycillin and the final group,
      pre-operative cefaclor. The qualitative bacteriology was similar in the three
      groups Haemophilus influenzae was the predominant isolate present in the centre
      ('core') of the resected tonsil. Similar numbers of beta-lactamase producers
      including H. influenzae and Straphylococcus aureus were found in all three
      groups. Quantitative bacteriology of the tonsil core demonstrated that there was
      a significant reduction in core tonsil pathogens associated with antibiotic
      therapy. The most statistically significant difference was between the untreated
      control group and the cefaclor treated group. We conclude that in patients with
      established recurrent acute tonsillitis, oral antibiotics penetrate the diseased
      tonsil and influence the predominant core aerobic microflora.

PMID- 8877233
TI  - Long-term results of vocal rehabilitation after total laryngectomy with the low
      resistance, indwelling Provox voice prosthesis system.
AB  - A low-resistance indwelling prosthesis for vocal rehabilitation after total
      laryngectomy, Provox was developed in the Netherlands Cancer Institute 5 years
      ago. The long-term results in 132 patients using this prosthesis are now
      reported. The mean and median device life of the prosthesis in the 75 patients in
      long-term follow-up are 235 and 141 days respectively. Good to fair vocal
      rehabilitation was achieved in 92% of the patients. Statistical analysis revealed
      a significant relationship of the device life with the original tumour site (P =
      0.0078). Radiotherapy had a borderline (P = 0.0652) negative influence on the
      device life but not on prosthesis-related complications. Increasing follow-up
      time has a positive influence on the device life of the prosthesis (P < 0.0001).

PMID- 8877234
TI  - The effect of budesonide (Rhinocort) in the treatment of small and medium-sized
      nasal polyps.
AB  - The objectives of this study were to determine if the size of nasal polyps could
      be assessed in a reproducible way and to study the effect of budesonide in
      patients suffering from eosinophilic nasal polyposis with small and medium sized
      polyps. Ninety-one patients entered the study. Budesonide 200 micrograms b.i.d.
      (aerosol or aqua) and placebo (aerosol or aqua) were compared in a 3-month double
      blind, multi-centre, randomized study. Efficacy was measured by an assessment of
      polyp size, nasal peak-flow index and the patient's assessment of nasal symptoms.
      The conclusions were that the size of polyps could be assessed in a reproducible
      way, and that budesonide delivered either as a water-based suspension or as an
      aerosol is effective in the treatment of patients with small and medium sized
      polyps.

PMID- 8877235
TI  - Primary lymphoma of mucosa associated lymphoid tissue (MALT) in the parotid
      gland.
AB  - Malignant lymphoma of the parotid gland is a rare condition. In a series of 365
      malignant lymphomas of the head and neck seven cases (1.9%) presented with a
      stage I/II MALT lymphoma of the parotid gland, originating from Mucosa Associated
      Lymphoid Tissue (MALT) and exhibiting the histological criteria of a centrocyte
      like cell proliferation, surrounding reactive B-cell follicles. There were six
      men and one woman with a mean age of 50.1 years. In four patients the parotid
      mass was present for more than one year. Complete remission was obtained by
      radiotherapy (40 Gy). Prognosis for this group was found to be favourable with a
      follow-up ranging from 1.5 to 10 years.

PMID- 8877236
TI  - Can audit improve the quality of care for routine tonsillectomy?
AB  - Tonsillectomy is the most commonly performed operation in otolaryngology
      practice. In order to assess outcome and improve quality of care, 65 patients
      were asked to answer a post-operative questionnaire. The questionnaire was then
      audited and patient management changed. Following this, another group of 65
      patients revealed, in the same questionnaire, a significant improvement in care.

PMID- 8877237
TI  - T3 laryngeal cancer, primary surgery vs planned combined radiotherapy and
      surgery.
AB  - The Dutch Co-operative Head and Neck Oncology Group performed a retrospective,
      nationwide study of laryngeal cancer between 1975 and 1984. The results for T3
      laryngeal cancer treated with primary laryngectomy (n = 137) with post-operative
      radiotherapy when indicated or planned combined (pre-operative) radiotherapy with
      laryngectomy (n = 113) are analysed. The disease-free survival independent
      prognostic factors were treatment modality (planned combined treatment fared
      better, P = 0.001), incomplete resection of disease (P = 0.006), positive lymph
      nodes in the neck dissection specimen (P = 0.03) and poor differentiation (P =
      0.04). Local control (95% vs. 85%, P = 0.01) as well as regional control (96% vs.
      79%, P = 0.0001) was improved in the combined group compared with the primary
      laryngectomy group. Regional control was 69% for N0 patients if the neck nodes
      were not treated electively, compared with 98% for the planned combined treatment
      group. It is concluded that elective treatment of the neck nodes in T3 laryngeal
      cancer is mandatory. Radiotherapy is preferred, since as well as regional
      control, local control will also improve.

PMID- 8877238
TI  - Royal College of Surgeons comparative ENT audit 1990.
AB  - The Royal College of Surgeons Comparative Audit Service was set up in 1990 so
      that surgeons could pool their audit data, to provide 'standards' with which to
      compare their own figures. A total of 405 consultant otolaryngologists were
      circularized in December 1991 inviting them to return data about their resources,
      workload, case-mix and complications, and about two specific audit topics
      Myringoplasty and Carcinoma of the Larynx--for the calendar year 1990. A total of
      65 consultants returned proformas with data on 52208 admissions and 31240
      surgical procedures. The 'average' respondent admitted 829 patients in the year
      (19% of these day cases and 14% emergencies) and performed 744 surgical
      procedures with a mean complication rate of 1.39% using three theatre sessions
      per week. Cancelled theatre sessions per annum per consultant ranged from 0 to
      71. The mean known success rate after myringoplasty was 65%, with hearing
      improvement in 53%. The 'average' ENT surgeon saw 3.5 new cases of invasive
      carcinoma of the larynx and treated 69% of these with radiotherapy alone,
      compared with 14% surgery alone. As well as allowing a profile to be drawn up of
      the 'average' respondent, this audit allowed individual consultants returning
      data to compare their own figures in detail with the pooled data, which were
      presented graphically at a meeting in April 1992.

PMID- 8877239
TI  - Treatment of acute gastroenteritis: too much and too little care.
AB  - This paper reviews the health services literature regarding care for
      gastroenteritis in children. United States health care utilization, use of oral
      rehydration therapy (ORT), and quality of care considerations are described. The
      literature suggests that some US children may receive too much care while others
      may not be getting enough and that physician practices continue to differ from
      expert recommendations.

PMID- 8877240
TI  - Etiology and outcome of outpatient fevers in pediatric heart transplant patients.
AB  - We reviewed 74 outpatient febrile episodes in 22 pediatric heart transplant
      patients in order to determine etiologies, rates of serious and nonserious
      illness, and factors predictive of serious disease. Twenty-two febrile episodes
      (30%) resulted in hospital admission. Only three variables were predictive of
      serious illness: longer duration of fever, shorter time since transplant, and
      lower febrile episode number. We conclude that at least 70% of outpatient febrile
      episodes are nonserious and can be managed safely in an outpatient setting. The
      duration of fever may be predictive of serious disease but is not useful at
      initial presentation.

PMID- 8877241
TI  - Sweeteners, dyes, and other excipients in vitamin and mineral preparations.
AB  - Multivitamins and mineral preparations are widely used for infants and children.
      All of these preparations contain a variety of excipients ("inert ingredients").
      Excipients are generally safe; however, adverse effects have been attributed to
      them. Complete information about the excipients in various preparations is not
      readily available. The information about sweeteners, dyes, and other excipients
      (flavorings, preservatives, stabilizers, and fillers) for 41 chewable/liquid
      multivitamin and mineral preparations was obtained and tabulated. Sucrose was
      present in 63% (26/41) of preparations followed by lactose in 29% (12/41) of
      preparations. On average, a preparation contained two sweeteners. The FD&C yellow
      #6 (sunset yellow) was the most common dye, present in 46% (19/41) of the
      preparations followed by FD&C Red #40 in 29% (12/41). For 34% (14/41) of the
      preparations, no color or dye was identified by the manufacturers. The tables
      listing excipients and their adverse effects are presented and should be helpful
      to health care providers in selecting preparations containing individual
      excipients when an adverse reaction occurs or there exists a contraindication for
      using the excipient. The mandatory listing of all excipients is the only way to
      assure that physicians and consumers will be fully informed about the hidden
      ingredients.

PMID- 8877242
TI  - Ranitidine therapy for esophagitis in children with developmental disabilities.
AB  - Esophagitis is common in children with cerebral palsy. Because histamine2
      receptor antagonists such as ranitidine have not been uniformly effective, we
      treated disabled children with esophagitis with greater than usual doses.
      Endoscopy and pH monitoring were used to monitor dose and response to treatment.
      A dose of 9.3 +/- 0.9 mg/kg/day did not improve visual or microscopic esophagitis
      after 3 months. A dose of 14.8 +/- 3.9 mg/kg/day resulted in only slight
      microscopic improvement, but symptoms were improved. There was no correlation
      between esophageal reflux index at enrollment and either severity of esophagitis
      or response to treatment. Elevation of gastric pH by ranitidine was infrequent.
      These results affirm that pH monitoring does not reliably identify disabled
      children with reflux esophagitis nor does ranitidine reliably heal this disorder.

PMID- 8877243
TI  - A double-blind, placebo-controlled trial of decongestant-antihistamine for the
      treatment of sinusitis in children.
AB  - We studied the effectiveness of nasal decongestant-antihistamine in treating
      acute sinusitis in children. All subjects received oral amoxicillin for 14 days.
      Subjects randomized to the decongestant-antihistamine group received nasal
      oxymetazolone and oral syrup containing brompheniramine and phenylpropanolamine.
      Controls received placebo nasal saline and oral syrup. In both groups symptoms
      resolved quickly, and radiographs improved significantly. Responses to treatment
      were similar between the two groups. Water's radiographs of the maxillary sinuses
      proved reliable in the assessment of the degree of sinus involvement. We conclude
      that decongestant-antihistamine need not be given to the child with acute
      maxillary sinusitis.

PMID- 8877244
TI  - Evaluation and treatment of the deformed and malformed auricle.
AB  - Auricular malformations begin within the first few weeks of intrauterine growth.
      Less severe deformational abnormalities occur from abnormal fetal positioning.
      They can be corrected early after birth by simple reshaping and molding. No
      longer should the pediatrician wait for minor deformities to resolve
      spontaneously. The protruding ear may not be present at birth but may develop and
      worsen during the first year. The most severe anomalies require complex
      multistage reconstructions after other concomitant anomalies are excluded. The
      pediatrician must be an integral part of this reconstructive team.

PMID- 8877245
TI  - Tourette's syndrome: the school experience.

PMID- 8877246
TI  - Pulmonary effects of household bleach ingestion in children.

PMID- 8877247
TI  - Integrating pharmacokinetics into point-of-care information systems.
AB  - Computer-based patient care information systems (PCIS) have emerged as an
      integral component of healthcare organisations. Currently, 4 models of PCIS
      exist: the centralised model, the hub-and-spoke model, the network model, and the
      distributed model. The centralised model has the advantage of a central patient
      database; however, a major disadvantage of this model is the inability to easily
      interface with other software packages. The hub-and-spoke model links satellite
      or feeder systems into a mainframe computer; thus, each satellite has the ability
      to work independently. This system is limited by the ability to interface
      satellite systems with the mainframe computer. The network model works via a
      local area network (LAN) using client server technology which allows for high
      speed data access and transfer. The network model does not provide an integrated
      view of patient information and can access only 1 host system at a time. The
      distributed model is similar to the network model in design but provides for data
      and system integration via relational databases. This allows for the creation of
      a central data repository and support for decision-support tools. Computer
      assisted decision support has the potential to significantly improve clinical
      decision-making. Six types of computer-assisted decision-support have been
      defined: alerting, interpreting, assisting, critiquing, diagnosing and managing.
      Software representing each type of decision-support software has been
      incorporated into clinical practice; however, with the exception of drug
      interaction programs, widespread incorporation of decision-support software into
      PCIS is uncommon. Clinical pharmacokinetic programs are a category of pharmacy
      related decision-support software, and current clinical pharmacokinetic software
      systems can be categorised as interpreting, assisting or critiquing decision
      support. Despite the potential for significant clinical contributions, the
      integration of clinical pharmacokinetic software into PCIS is uncommon. Most
      packages are available only as stand alone programs or as a module of a pharmacy
      information system. These packages usually maintain their own centralised
      database and require special file transfer protocols for integration. Although
      PCIS are becoming more commonplace, the integration of commercial clinical
      pharmacokinetic packages into PCIS is limited. New technology using standardised
      and relational databases should allow for easier integration in the future.

PMID- 8877248
TI  - Clinical pharmacokinetics of rocuronium bromide.
AB  - A new aminosteroidal neuromuscular blocking agent, rocuronium bromide, has
      recently been introduced into clinical practice. Its main advantage over other
      currently used drugs of this kind is its fast onset of action, which could render
      rocuronium the muscle relaxant of choice for rapid facilitation of tracheal
      intubation. A further advantage of the new compound over vecuronium bromide is
      the less extensive formation of breakdown products, reducing the contribution of
      active metabolites to the neuromuscular blocking effects of the parent compound.
      Thorough knowledge of the pharmacokinetics of any new drug is highly desirable
      for the anaesthesiologist because absorption, distribution to the tissue, as well
      as elimination by biotransformation and excretion, are closely related to its
      effects. Due to its chemical relationship to other aminosteroidal neuromuscular
      blocking agents such as pancuronium bromide or vecuronium, rocuronium is expected
      to display pharmacokinetic behaviour similar to that of its predecessors. Hepatic
      and renal disease may prolong the effect of rocuronium, but to a lesser extent
      than seen with pancuronium or vecuronium, because the plasma clearance of
      rocuronium is not significantly influenced by dysfunction of the liver or
      kidneys. On the contrary, in elderly or hypothermic patients the reduction in
      plasma clearance results in a prolonged duration of the action of rocuronium. All
      information on the pharmacokinetics of this new nondepolarising neuromuscular
      blocking agent which has been made available to date is presented in this review,
      with a discussion of the significance of these data for clinical use of the drug.

PMID- 8877249
TI  - Clinical pharmacokinetics of vinorelbine.
AB  - Vinorelbine (5'-noranhydrovinblastine) is a recently developed semisynthetic
      anticancer drug which belongs to the Catharanthus alkaloid family. Its mechanism
      of action is only partially known but it is assumed that it acts, like
      vinblastine and vincristine, as an antimicrotubule agent arresting cell division
      in mitosis. Clinically, vinorelbine has mainly shown activity in the treatment of
      advanced non-small-cell lung cancer and the treatment of metastatic breast
      cancer. Early pharmacokinetic data were obtained with radioactive assays (radio
      immunoassay or 3H-labelled vinorelbine), then with more selective high
      performance liquid chromatographic techniques. Vinorelbine is usually
      administered intravenously but there has also been some experimentation with an
      oral formulation. The bioavailability of a liquid filled gelatin capsule ranges
      between 12 and 59% with a mean value of 27% [standard deviation (SD) 12%].
      Vinorelbine is rapidly absorbed with peak serum concentration reached within 2
      hours. In vitro, vinorelbine is mainly distributed into the blood cells,
      especially platelets (78%) and lymphocytes (4.8%) The unbound blood fraction is
      around 2%. In lung tissue vinorelbine concentrations are much higher than in
      serum, by up to 300-fold 3 hours after administration. Little is known about the
      biotransformation of vinorelbine. Desacetylvinorelbine is considered to be a
      minor metabolite and is only found in urine fractions, representing 0.25% of the
      injected dose. Urinary excretion of vinorelbine is low, accounting for less than
      20% of the dose. Faecal elimination has been demonstrated in 2 patients who were
      administered 3H-labelled vinorelbine; the amount of radioactivity recovered in
      the faeces was 33.9 and 58.4% for the 2 patients, respectively. The
      pharmacokinetic profile of vinorelbine is often described as a 3-compartment
      model characterised by a long terminal half-life (t1/2) that varies between 20
      and 40 hours and a large apparent volume of distribution (Vd) of around 70 L/kg.
      Systemic clearance ranges between 72.54 and 89.46 L/h (1209 and 1491 ml/min) when
      determined by high performance liquid chromatography and is higher than that
      reported by radioimmunoassay [46.2 L/h (770 ml/min)]. This could be due to the
      greater specificity of the chromatographic method. Vinorelbine has been
      administered by continuous intravenous infusion over 4 days. Steady-state was
      reached and the concentrations obtained were above the in vitro IC50
      (concentration of drug causing 50% inhibition). The effect of liver disease on
      vinorelbine pharmacokinetics has been studied in patients with breast cancer.
      Patients with massive secondary liver disease had a lower systemic clearance than
      those who have no liver disease or a lesser invasion. In children, vinorelbine
      seems to display a shorter t1/2 (14.7 hours) than that found in adults. In
      addition, the systemic clearance is highly variable [from 12 to 93.96 L/h/m2 (200
      to 1566 ml/min/m2)]. Vinorelbine is often co-administered with cisplatin in the
      treatment of advanced non-small-cell lung cancer. The disposition of the alkaloid
      is not altered by concurrent administration of cisplatin.

PMID- 8877252
TI  - Pharmacokinetic rationale for chemotherapeutic drugs combined with intra-arterial
      degradable starch microspheres (Spherex).
AB  - To enhance the effectiveness of regional treatment in patients with liver
      carcinoma, cytotoxic drugs may be combined with alternative therapeutic
      strategies such as partial vascular blockade using degradable starch microspheres
      (DSM). When DSM combined with a cytotoxic drug are infused through the hepatic
      artery, the steep drug concentration gradient to the tumour tissue results in
      higher tissue drug concentrations which may elicit an increased antitumour
      response. The co-injected drug should therefore possess an extensive
      extravascular distribution and possess a suitable dose-response relationship.
      Furthermore, the drug of choice should also have a high total body clearance with
      a large component of clearance outside the target compartment, should not
      interact with the spheres and should be given without inducing any back-flow.
      Under these assumptions, a reduced systemic exposure of a co-injected drug could
      be translated into an increased regional extraction ratio induced by the blood
      flow reduction.

PMID- 8877253
TI  - The clinical investigator as target.

PMID- 8877251
TI  - Idiosyncratic drug reactions. Metabolic bioactivation as a pathogenic mechanism.
AB  - The metabolism of drugs to chemically reactive metabolites may play a pivotal
      role in the pathogenesis of idiosyncratic drug toxicity. A large number of in
      vitro studies and a limited number of in vivo studies have demonstrated that many
      drugs are not toxic per se, but produce toxicity after undergoing enzyme-mediated
      bioactivation to chemically reactive species. Such reactive species may inflict a
      toxic insult on the cell either directly or indirectly by acting as a hapten and
      initiating an immune-mediated reaction. The enzymes responsible for bioactivation
      have been widely studied, both quantitatively and qualitatively, the most
      important being the enzymes of the cytochrome P450 (CYP) mixed function oxidase
      system. CYP enzymes are the most predominant drug metabolising enzymes in the
      liver and are also present in most other tissues of the body. The diversity of
      this enzyme system means that a wide range of xenobiotic substrates can be
      bioactivated by either a single CYP isoform or multiple isoforms of this enzyme
      superfamily. Other enzymes do, however, play an important role in drug
      bioactivation. In white blood cells, for example, myeloperoxidase has been shown
      to bioactivate a wide range of drugs. In other tissues low in CYP activity,
      prostaglandin H synthase may also be responsible for bioactivation; e.g. in the
      kidney paracetamol (acetaminophen) toxicity is though to result from activation
      via this enzyme. The phase II or conjugation enzymes may also be important in the
      ultimate bioactivation of drug molecules. Whilst activation by these enzymes is,
      to date, apparently confined to chemicals, most drugs are also substrates for
      these enzymes and bioactivation by them must remain a possibility.

PMID- 8877250
TI  - Clinically significant pharmacokinetic drug interactions with carbamazepine. An
      update.
AB  - Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is
      also used in the treatment of trigeminal neuralgia and psychiatric disorders,
      particularly bipolar depression. Because of its widespread and long term use,
      carbamazepine is frequently prescribed in combination with other drugs, leading
      to the possibility of drug interactions. The most important interactions
      affecting carbamazepine pharmacokinetics are those resulting in induction or
      inhibition of its metabolism. Phenytoin, phenobarbital (phenobarbitone) and
      primidone accelerate the elimination of carbamazepine, probably by stimulating
      cytochrome P450 (CYP) 3A4, and reduce plasma carbamazepine concentrations to a
      clinically important extent. Inhibition of carbamazepine metabolism and elevation
      of plasma carbamazepine to potentially toxic concentrations can be caused by
      stiripentol, remacemide, acetazolamide, macrolide antibiotics, isoniazid,
      metronidazole, certain antidepressants, verapamil, diltiazem, cimetidine, danazol
      and (dextropropoxyphene) propoxyphene. In other cases, toxic symptoms may result
      from elevated plasma concentrations of the active metabolite carbamazepine-10,11
      epoxide, due to the inhibition of epoxide hydrolase by valproic acid (sodium
      valproate), valpromide, valnoctamide and progabide. Carbamazepine is a potent
      inducer of CYP3A4 and other oxidative enzyme system in the liver, and it may also
      increase glucuronyltransferase activity. This results in the acceleration of the
      metabolism of concurrently prescribed anticonvulsants, particularly valproic
      acid, clonazepam, ethosuximide, lamotrigine, topiramate, tiagabine and
      remacemide. The metabolism of many other drugs such as tricyclic antidepressants,
      antipsychotics, steroid oral contraceptives, glucocorticoids, oral
      anticoagulants, cyclosporin, theophylline, chemotherapeutic agents and
      cardiovascular drugs can also be induced, leading to a number of clinically
      relevant drug interactions. Interactions with carbamazepine can usually be
      predicted on the basis of the pharmacological properties of the combined drug,
      particularly with respect to its therapeutic index, site of metabolism and
      ability to affect specific drug metabolising isoenzymes. Avoidance of unnecessary
      polypharmacy, selection of alternative agents with lower interaction potential,
      and careful dosage adjustments based on serum drug concentration monitoring and
      clinical observation represent the mainstays for the minimisation of risks
      associated with these interactions.

PMID- 8877254
TI  - Randomized clinical trials in the presence of diagnostic uncertainty:
      implications for measures of efficacy and sample size.
AB  - Diagnostic uncertainty, particularly prior to the receipt of test results, is
      common in medicine. When randomized trials are being conducted to evaluate
      therapies in these situations, patients must be randomized in the absence of a
      definitive diagnosis. This article explores some of the implications of
      diagnostic uncertainty for the design and analysis of randomized clinical trials,
      using specific therapeutic examples to illustrate the important points.

PMID- 8877255
TI  - Ethical and cross cultural questions concerning pediatric clinical trials.
AB  - During a clinical trial of recombinant growth hormone in a population of short
      stature but otherwise healthy children the following ethical problems were
      confronted: What are the prospective benefits compared with the foreseeable risks
      associated with this therapy? Can the doctor really inform the parent and/or the
      child about the outcomes of the treatment? Who must make the decision about
      participation in the trial? From which age can the child himself decide about
      continuing or dropping out? Since the treatment requires frequent check-ups for
      years, to what extent does the child become psychologically dependent upon the
      medical profession? Given this possibility, is the child really free to withdraw
      from the treatment? Is there a conflict between the doctor's autonomy to propose
      the treatment and the patient's autonomy to decide about participation? Is there
      a clear threshold between life-threatening problems and minor, cosmetic problems?
      These dilemmas are discussed in a cross-cultural context.

PMID- 8877256
TI  - A factorial survey study to assess the acceptability of HIV vaccine trial
      designs.
AB  - To aid in the design of human immunodeficiency virus (HIV) vaccine trials that
      maximize volunteer participation, factorial surveys were administered to 73 gay
      men who were participants in a larger study assessing HIV vaccine trial
      feasibility. Factorial surveys are "vignettes" that are randomly constructed
      through the combination of descriptive statements (dimensions) that reflect
      essential features. In this study, the dimensions define components of clinical
      trials to assess the efficacy of hypothetical HIV vaccines. Regression analysis
      shows that anticipated participation was decreased by a sustained vaccine-induced
      antibody response lasting 3 years, absence of gay men as research subjects in
      earlier phase trials for the products being tested, and rectal vaccine
      administration. Three years of scientific experience with the vaccine encouraged
      participation. We conclude that willingness to participate in vaccine trials
      varies systematically with some of their characteristics. Where there are design
      alternatives for identified negative components, these should be considered. If
      this is not possible, options for decreasing aversion to such features will need
      to be evaluated, including appropriate education regarding both the benefits and
      the risks associated with negatively evaluated features.

PMID- 8877257
TI  - Sample size calculations for within-patient comparisons with a binary or survival
      endpoint.
AB  - Formulae are derived for the required number of failures needed in a randomized
      clinical trial with a binary or survival endpoint in which treatments are
      compared using multiple units within each patient. Calculation of the required
      total numbers of units and patients are illustrated by examples. These show that
      naive use of conventional calculations could underestimate the number of units
      and patients required, particularly if the number of units per patient is small.

PMID- 8877258
TI  - Organizational structure and communication strategies of the bypass angioplasty
      revascularization investigation: a multicenter clinical trial.
AB  - Efficient communication is a challenge for the many operating components of a
      multicenter randomized clinical trial. Traditional management theory states that
      communications generally flow along a path established by a hierarchical
      organizational structure. A multicenter clinical trial does not fit traditional
      organizational models well and requires modification of traditional communication
      techniques. While the scientific community typically views a clinical trial as
      one large and cohesive enterprise, at each site the trial may actually be
      conducted as a small project related to the medical specialty of the
      investigator. Therefore overall trial management must be accomplished through
      collaboration rather than through direct management. In the Bypass Angioplasty
      Revascularization Investigation (BARI), the BARI clinical coordinating center has
      designed and utilized several mechanisms that facilitate effective communication
      and administrative control of a multicenter clinical trial. These mechanisms
      provide a framework of communication techniques that accommodate the specific
      needs of a complex organization.

PMID- 8877259
TI  - Development of a prospective register of smoking cessation trials.

PMID- 8877260
TI  - Baseline characteristics of participants in the Appropriate Blood Pressure
      Control in Diabetes trial.
AB  - The ABCD (Appropriate Blood Pressure Control in Diabetes) trial is a large,
      prospective, randomized clinical trial designed to compare the effects of
      intensive with moderate blood pressure control on the prevention and progression
      of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in
      non-insulin-dependent diabetes (NIDDM). The secondary objective is to determine
      equivalency of the effects of a calcium channel blocker (nisoldipine) and of an
      angiotensin-converting enzyme inhibitor (enalapril) as a first-line
      antihypertensive agent in the prevention and/or progression of these diabetic
      vascular complications. The study consists of two study populations: a
      hypertensive one (diastolic blood pressure of > or = 90.0 mm Hg at the time of
      randomization) and a normotensive one (diastolic blood pressure of 80.0-89.0 mm
      Hg at the time of randomization). A total of 950 men and women aged 40-74 years
      were randomized and are being followed for 5 years at a single center. There were
      470 randomized participants in the hypertensive population and 480 randomized
      participants in the normotensive population. This report summarizes the
      demographic, biochemical, and clinical characteristics of the randomized patients
      at the time of entry into the trial and evaluates the balance between the
      treatment groups within each population.

PMID- 8877261
TI  - Differences in basal nocturnal, meal-stimulated, and pentagastrin-stimulated
      gastric secretion values in a sample of healthy volunteers in basal conditions
      and under ranitidine influence.
AB  - The gastric secretion values from 16 healthy male volunteers are reported. A
      nasogastric tube was positioned in the gastric antrum and 10-min gastric
      secretion samples were obtained hourly by continuous suction. Basal nocturnal,
      meal-stimulated, and pentagastrin-stimulated gastric acid secretion were
      measured. Experimental sessions were carried out in control conditions and
      repeated after a 7-day treatment with placebo and ranitidine (150 mg b.i.d.) in a
      double-blind procedure. We found six subjects (group I) with basal nocturnal,
      meal-stimulated, and pentagastrin-stimulated gastric secretion values
      statistically lower than then rest of the group (group II). Basal nocturnal
      secretion mean values were 3.99 +/- 6.6 mmol/L (group I) and 59.2 +/- 22.1 mmol/L
      (group II) (p < 0.01). Meal-stimulated gastric acidity mean values were 33.1 +
      17.3 mmol/L (group I) and 65.6 +/- 30.6 mmol/L (group II) (p < 0.05).
      Pentagastrin-stimulated gastric secretion mean values were 8 +/- 2 mmol/h (group
      I) and 19.2 +/- 2.7 mmol/h (group II) (p < 0.01). Ranitidine significantly
      inhibited basal nocturnal, meal-stimulated, and pentagastrin-stimulated gastric
      acidity values mostly in group II. These results suggest that there are two
      different patterns of gastric secretion in the healthy male population.

PMID- 8877262
TI  - Sudden cardiac death: lessons from multicenter clinical trials.

PMID- 8877263
TI  - Clinical trials of arrhythmia management: methods or madness.
AB  - Some randomized controlled clinical trials (RCTs) involving antiarrhythmic agents
      have recently reported unexpected findings. Cardiologists have tried to explain
      these unforeseen results by pointing to possible inadequacies of trial design.
      Details of the design and the conduct of RCTs are essential for the proper
      interpretation of the data that emerge from the trial. Unless an RCT is carefully
      designed and meticulously conducted, the results may be difficult to interpret.
      Some trials of antiarrhythmic drugs and management strategies have had design
      faults that have complicated the interpretation of the trial data. Clinical trial
      results are only one component of the body of knowledge that clinicians must use
      when they plan patient management and prescribe therapies. Data from the basic
      sciences, other branches of medicine, personal experience, and clinical trials
      must all be available in order to reach the best decision. It is inappropriate to
      rely exclusively on the results of clinical trials because individual patients
      and their problems rarely, if ever, fully match the characteristics of patients
      enrolled into clinical trials. However, data from good RCTs should form an
      important base for clinical decision making.

PMID- 8877264
TI  - Post-myocardial infarction trials: beta blockers, antiarrhythmics, thrombolytics.
AB  - This paper reviews trials of postmyocardial infarction therapies including beta
      adrenergic blockers, antiarrhythmic agents other than amiodarone, and
      thrombolytic drugs. The results of certain beta blockers on overall
      cardiovascular mortality and sudden death mortality after myocardial infarction
      are discussed, along with the results of CAST and subgroup analyses on patients
      at high risk for death. The effects of thrombolysis during acute myocardial
      infarction on subsequent arrhythmic mortality are also reviewed.

PMID- 8877265
TI  - Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM): a
      critical appraisal.
AB  - This paper reviews the Electrophysiologic Study versus Holter Monitoring (ESVEM)
      trial, addressing several areas of concern including potential enrollment bias,
      an inadequate electrophysiologic testing protocol during drug therapy, and an
      unexpectedly high recurrence rate in patients deemed to be controlled by either
      method. The paper concludes that there are insufficient data to warrant
      extrapolation of the ESVEM results to survivors of cardiac arrest.

PMID- 8877266
TI  - Major clinical trials assessing the prophylactic use of amiodarone in patients
      with ventricular tachyarrhythmias.
AB  - The purpose of this article is to summarize and critique recently completed and
      ongoing clinical trials assessing the prophylactic use of amiodarone in patients
      with potentially life-threatening ventricular arrhythmias. Three of the trials
      compare amiodarone with an implantable cardioverter defibrillator.

PMID- 8877267
TI  - Ongoing risk stratification trials: the primary prevention of sudden death.
AB  - This paper reviews three ongoing risk stratification trials: the Coronary Artery
      Bypass Grafting-Patch Trial (CABG-Patch), the Multicenter Automatic Implantable
      Defibrillator Trial (MADIT), and the Multicenter Unsustained Tachycardia Trial
      (MUSTT).

PMID- 8877268
TI  - Nuclear magnetic resonance (NMR) analysis of ligand receptor interactions: the
      cholinergic system--a model.
AB  - Elucidation of the molecular mechanisms that govern ligand-receptor recognition
      is essential to the rational design of specific pharmacological reagents. Whereas
      often the receptor and its binding site are the target of investigation, study of
      the ligand in its free and bound state can also reveal important information
      regarding this recognition process. Nuclear magnetic resonance (NMR) spectroscopy
      can be extremely useful for such studies. In this review, we discuss the
      attributes of NMR in the study of ligand receptor interactions. The cholinergic
      receptor and its binding to the neurotransmitter, acetylcholine, and cholinergic
      antagonists serve as a model system, illustrating the power of ligand analysis by
      NMR. The results discussed prove that the region of residues alpha 180-205 of the
      nicotinic acetylcholine receptor are an essential component of the cholinergic
      binding site and that ligand binding involves a positively charged hydrophobic
      motif.

PMID- 8877269
TI  - The chloride pump: a Cl(-)-translocating P-type ATPase.
AB  - Three widely documented mechanisms of chloride transport across plasma membranes
      are anion-coupled antiport, sodium-coupled symport, and an electrochemical
      coupling process. No direct genetic evidence has yet been provided for primary
      active chloride transport despite numerous reports of cellular Cl(-)-stimulated
      adenosine triphosphate (ATP)ases coexisting in the same tissue with uphill
      chloride transport that could not be accounted for by the three common chloride
      transport processes. Cl(-)-stimulated ATPases are a common property of
      practically all biological cells, with the major location being of mitochondrial
      origin. It also appears that plasma membranes are sites of Cl(-)-stimulated
      ATPase activity. Recent studies of Cl(-)-stimulated ATPase activity and chloride
      transport in the same membrane system, including liposomes, suggest a mediation
      by the ATPase in net movement of chloride up its electrochemical gradient across
      plasma membranes. Further studies, especially from a molecular biological
      perspective, are required to confirm a direct transport role to plasma membrane
      localized Cl(-)-stimulated ATPases.

PMID- 8877270
TI  - Dyslipidemia in diabetes mellitus.
AB  - Patients with diabetes mellitus have a higher rate of mortality than the general
      population. This higher mortality may be attributed mainly to cardiovascular
      disease. A high prevalence of dyslipidemia in diabetics can be one of the reasons
      for this. The most commonly recognized lipid abnormality in non-insulin-dependent
      diabetics (NIDDM) is hypertriglyceridemia, which is known to be an independent
      risk factor for coronary heart disease in diabetics. Hypertriglyceridemia can be
      produced by two mechanisms, increased synthesis of very-low-density lipoprotein
      (VLDL) triglyceride and removal defect of plasma triglyceride. It has been a
      matter of debate whether insulin always stimulates hepatic VLDL secretion but it
      is generally accepted that insulin deficiency results in an impairment of plasma
      triglyceride clearance. Considerable attention has recently been focused on the
      atherogenecity of postprandial hyperlipidemia, remnant lipoproteins, small, dense
      LDL, lipoprotein (a) [Lp(a)] and isolated hypo-alphalipoproteinemia in NIDDM
      subjects. Several reports suggested that these atherogenic lipoprotein
      abnormalities are present in NIDDMs even if they are apparently normolipidemic.
      Association of visceral fat obesity, insulin resistance and nephropathy may
      aggravate the atherogenic lipoprotein profile. Therefore, we propose here that
      plasma lipid levels of diabetic subjects must be more strictly controlled than
      for the non-diabetic population in order to avoid an increased risk for coronary
      heart disease. If they are obese or associated with insulin resistance or
      nephropathy, these conditions should be carefully controlled.

PMID- 8877271
TI  - Acarbose partially prevents the development of diabetes mellitus by multiple low
      dose streptozotocin administration.
AB  - Prophylactic insulin treatment prevents the development of hyperglycemia in
      animal models of insulin-dependent diabetes mellitus. Acarbose is a new
      antidiabetic drug which improves hyperglycemia by inhibiting alpha-glucosidase.
      In the present study, we determined the preventive effect of acarbose against
      multiple low-dose streptozotocin (MLDSTZ)-induced diabetes mellitus. The male ICR
      mice were fed acarbose (40 mg/100 g) containing powdered chow before the start of
      STZ administration. The mice were sacrificed at 3 and 10 days after the final STZ
      injection. MLDSTZ decreased serum immunoreactive insulin (IRI) levels and
      increased plasma glucose levels. Acarbose administration tended to decrease
      plasma glucose and serum IRI levels were significantly reduced in vehicle-treated
      mice. Acarbose administration significantly attenuated the degree of inflammation
      and destruction in pancreatic islets after MLDSTZ administration. In conclusion,
      acarbose-induced attenuation of acute hyperglycemia following MLDSTZ partially
      prevents the severity of pancreatic islet damage.

PMID- 8877272
TI  - Studies on the impact of dietary fat composition on proteinuria in diabetic rats.
AB  - Rats with streptozotocin diabetes were pair-fed diets containing 20% beef tallow
      (BT), fish oil (FO), or safflower oil (SO) for up to six months. After one month,
      differences in glucose control were not observed but rats fed FO had more renal
      hypertrophy. FO reduced glomerular prostaglandin E2 and 6-keto F1 alpha, and BT
      increased thromboxane B2 production, but there were no differences in glomerular
      filtration rate (GFR) or renal plasma flow (RPF). Animals fed BT needed more
      insulin after two months than rats fed FO followed by SO. After six months,
      diabetic rats fed FO had larger relative kidney weights than SO or BT, but a
      similar pattern was present in non-diabetic controls fed the same diets. Diabetic
      rats fed BT had more proteinuria than diabetic rats fed SO but not FO. However,
      FO-fed controls had more proteinuria than controls fed SO and similar levels of
      proteinuria as diabetic rats fed FO. The composition of dietary fat alters
      glucose tolerance in diabetic rats after two months. BT increases glomerular
      thromboxane production and hastens proteinuria compared to SO. FO enhances renal
      growth and proteinuria, but this effect is independent of the diabetic condition.

PMID- 8877273
TI  - Increased white cell aldose reductase mRNA levels in diabetic patients.
AB  - This paper examines the question of whether diabetes in humans is associated with
      changes in aldose reductase and sorbitol dehydrogenase gene expression. The
      polyol pathway, which comprises the enzymes aldose reductase and sorbitol
      dehydrogenase, is recognised to play a central role in the pathogenesis of the
      diabetic complications. Whilst it is known that experimental diabetes in the rat
      is associated with increased aldose reductase gene expression, possibly as an
      osmoregulatory response to hyperglycaemia, little is known about aldose reductase
      and sorbitol dehydrogenase gene expression in diabetes in humans. White cell
      aldose reductase mRNA levels were increased in patients with insulin-dependent
      (by 135%, P < 0.05) and non-insulin-dependent (by 132%, P < 0.05) diabetes
      compared to levels in healthy volunteers. Levels of glycosylated haemoglobin were
      also increased (P < 0.001) in diabetes but there was no correlation between white
      cell aldose reductase mRNA and glycosylated haemoglobin levels. In contrast to
      aldose reductase, levels of white cell sorbitol dehydrogenase mRNA were not
      affected by diabetes. These results establish for the first time that diabetic
      patients show increases in white cell aldose reductase mRNA levels, possibly
      consistent with increased aldose reductase gene expression. This finding may have
      implications for the use of aldose reductase inhibitors in the treatment of the
      diabetic complications.

PMID- 8877274
TI  - No evidence of increased fetal haemoglobin in an adult diabetic population.
AB  - Increased fetal haemoglobin levels, which could interfere with glycohaemoglobin
      assessment, have been observed in some diabetic populations, especially in
      insulin-treated patients. In this study, we have consecutively examined 1042
      adult (aged > 18 y) diabetic subjects (102 IDDM patients, 263 insulin-treated
      NIDDM patients and 677 non-insulin-treated NIDDM patients) and 156 sex-and age
      matched control subjects. Fetal haemoglobin was assessed with a fully automated
      high performance liquid chromatography (HPLC) device. Its average levels were
      0.19% +/- 0.28% in the control group, 0.17% +/- 0.23% in IDDM patients, and 0.19%
      +/- 0.25% in insulin-treated NIDDM patients; these differences were not
      significant. Also the percentage of patients with fetal haemoglobin exceeding the
      95th percentile of normal values (0.75%) was not different in the various
      subgroups. In conclusion, in our large cohort of adult diabetic patients, fetal
      haemoglobin levels are within the normal range, including those who have IDDM or
      insulin-treated NIDDM. Genetic factors could explain this difference with other
      reports.

PMID- 8877275
TI  - Effect of manidipine and delapril on insulin sensitivity in type 2 diabetic
      patients with essential hypertension.
AB  - The open trial was designed to evaluate the effects of long-term antihypertensive
      treatment with the calcium-channel blocker, manidipine and the angiotensin
      converting enzyme (ACE) inhibitor, delapril on insulin sensitivity in Japanese
      non-insulin dependent diabetes mellitus (NIDDM) patients with essential
      hypertension. We measured the insulin sensitivity index (SI) and the glucose
      effectiveness (SG) by the use of Bergman's minimal model method in 18
      hypertensive NIDDM patients before and after administration of manidipine (group
      A) or delapril (group B) for 3 months. Manidipine treatment for 3 months
      significantly improved SI in group A from 3.35 +/- 0.61 (x 10(-4) min-1 microU-1
      ml-1) to 4.70 +/- 1.34 (P < 0.05). Delapril treatment for 3 months also
      significantly improved SI in group B from 3.56 +/- 1.04 to 5.00 +/- 0.87 (P <
      0.05). Manidipine significantly improved SG in group A from 1.60 +/- 0.64 (x 10(
      2) min) to 2.19 +/- 0.38 (P < 0.05). Delapril treatment also significantly
      improved SG in the group B from 1.41 +/- 0.56 to 1.91 +/- 0.35 (P < 0.05).
      Manidipine and delapril did not affect urinary C-peptide excretion for 24 h in
      the hypertensive NIDDM patients. Treatment with manidipine or delapril
      significantly reduced systolic and diastolic blood pressures in the hypertensive
      NIDDM patients. There were no differences between plasma glucose, serum total
      triglycerides, and cholesterol or lipoprotein cholesterol fractions, heart rate
      and body weight after 3 months on manidipine or delapril. This study confirmed
      the improving effects on SI and SG by long-term treatment with manidipine or
      delapril in the hypertensive NIDDM patients.

PMID- 8877276
TI  - Different effect of acute and chronic oral metformin administration on glucose
      and insulin response to bread and to pasta in non-insulin dependent diabetic
      patients.
AB  - The aim of the study was to evaluate whether acute and chronic metformin
      administration may influence differently the glycaemic and insulin response to
      foods with high and low glycaemic index (bread and pasta) in twelve non-insulin
      dependent diabetic (NIDDM) patients. Thirty minutes after a random oral
      administration of either a placebo or a single 850 mg metformin dose, glycaemic
      and insulin responses to 90 g white bread or 68 g pasta (corresponding to 50 g
      carbohydrates) were evaluated within 4 h. All the patients were subsequently
      treated with metformin (850 mg twice a day) for a month and then glycaemic and
      insulin responses were evaluated again. The acute administration of metformin
      lowered glycaemic response to bread at 60 and 90 min (P < 0.02 and P < 0.05,
      respectively) but not to pasta, without affecting insulin response. Chronic
      metformin treatment significantly lowered glycaemic and insulin response to both
      bread and pasta. In conclusion, an acute antihyperglycaemic effect of metformin
      was demonstrable only when a food with high glycaemic index, such as bread, was
      eaten. On the contrary, the effect of chronic treatment was always present,
      independent from the glycaemic index of foods, together with a reduction in
      insulin response, indicating an enhanced sensitivity to endogenous insulin.

PMID- 8877277
TI  - Effect of nifedipine, captopril and prazosin on secretory function of pancreatic
      beta-cells in hypertensive patients with type-2 (non-insulin-dependent) diabetes
      and in hypertensive non-diabetics.
AB  - The aim of our study was to compare the effect of captopril--the angiotensin
      converting enzyme inhibitor, nifedipine--the calcium antagonist, and prazosin-
      the alpha blocker, on the secretory function of pancreatic beta-cells in
      hypertensive patients with NIDDM and with normal glucose tolerance. The effect of
      a 2-week treatment with nifedipine, captopril and prazosin upon glycaemia, serum
      insulin (IRI) and C-peptide (CP) following oral and intravenous glucose load were
      investigated in three groups, each including 10 non-diabetic patients with
      essential hypertension (h) and 10 hypertensive type 2 (non-insulin-dependent)
      diabetics (h + d), aged 32-63 years. Nifedipine produced increase in glycaemia in
      the oral test in both groups. In the (h) group, but not in the (h + d) group, the
      drug caused reduction of the glucose-dependent increases in serum IRI and CP,
      more marked with respect to CP, as expressed by the decrease in the molar serum
      CP/IRI ratio. These results indicate that in non-diabetic patients, nifedipine
      reduces the early response of beta-cells to glucose, but this effect is partly
      compensated by a decreased insulin uptake by the liver. In patients with type 2
      diabetes, this phenomenon does not become manifest because of absence or
      reduction in the early glucose-dependent insulin release. After captopril, lower
      values of glycaemia and serum IRI and CP were observed in both groups suggesting
      an improvement of insulin sensitivity. In conclusion, nifedipine has a small
      influence, and captopril and prazosin are devoided of any influence on the
      secretory function of pancreatic beta-cells. These drugs may be recommended for
      the treatment of hypertension in patients with type 2 (non-insulin-dependent)
      diabetes.

PMID- 8877278
TI  - Induction of beta-cell neogenesis by islet injury.

PMID- 8877279
TI  - The BB/Wor rat and the balance hypothesis of autoimmunity.

PMID- 8877280
TI  - Superantigens of mouse mammary tumour virus: implications for diabetes?

PMID- 8877281
TI  - The use of immunological markers in IDDM after more than 20 years from ICA
      description.

PMID- 8877282
TI  - Prevention of insulin-dependent diabetes: where are we now?

PMID- 8877283
TI  - Islet transplantation: an update.

PMID- 8877285
TI  - Endothelin-1 stimulates insulin secretion by direct action on the islets of
      Langerhans in mice.
AB  - Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, is
      secreted in response to insulin. Elevated circulating ET-1 levels have been found
      in patients with diabetes mellitus and vascular dysfunction. The question arises
      whether ET-1 acts as a direct modulator of insulin secretion. To test this, we
      studied the effects of ET-1 on isolated mouse islets of Langerhans. ET-1 (1
      nmol/l-1 mumol/l) dose-dependently stimulated insulin secretion from islets
      incubated in the presence of 16.7 mmol/l glucose (p < 0.05). The effect of ET-1
      is glucose-dependent since no potentiation was found at 3.3 mmol/l glucose.
      Furthermore, ET-1 induced a large, transient increase in glucose-stimulated
      insulin secretion during islet perifusion in the presence (p < 0.001), but not in
      the absence, of extracellular Ca2+. The rate of 45Ca(2+)-efflux from 45Ca(2+)
      prelabelled islets was transiently stimulated by ET-1 during perifusion at 16.7
      mmol/l glucose in the presence of extracellular Ca2+ (p < 0.001). A short-lived
      increase in 45Ca(2+)-efflux was also observed in the absence of extracellular
      Ca2+ (p < 0.05). It is suggested that the effects of ET-1 on insulin secretion
      are critically dependent on influx via Ca(2+)-channels. In addition, ET-1
      transiently enhanced 86Rb(+)-efflux from 86Rb(+)-prelabelled islets both in the
      presence (p < 0.001) and in the absence (p < 0.001) of extracellular Ca2+
      suggesting that ET-1 does not elicit insulin secretion by inhibition of the
      potassium permeability. Our study provides evidence that ET-1 stimulates insulin
      secretion via a direct effect on the islets of Langerhans.

PMID- 8877286
TI  - Nitric oxide in ischaemic acute renal failure of streptozotocin diabetic rats.
AB  - Changes in nitric oxide (NO) levels were determined in ischaemic acute renal
      failure in streptozotocin-induced diabetes mellitus rats. Two weeks after
      streptozotocin administration and immediately after right nephrectomy, the left
      renal artery was occluded for 60 min. Similar procedures were carried out in non
      diabetic rats. The nitrite (NO2) + nitrate (NO3) levels were measured in plasma
      and urine. The effects of chronic oral supplementation with L-arginine and an NO
      synthase inhibitor (N-omega-nitro-L-arginine) were also studied in both diabetic
      and non-diabetic rats before and after renal artery clamping. The rats with
      diabetic acute renal failure had a much lower creatinine clearance (90 +/- 22
      microliters.min-1. 100g body weight-1, p < 0.005), and higher fractional
      excretion of sodium (FENa)% (10.90 +/- 4.2, p < 0.001) and protein excretion
      (2078 +/- 69 micrograms/ml creatinine clearance, p < 0.001) compared with the
      respective values in the non-diabetic groups (163 +/- 30; 1.46 +/- 86; 453.3 +/-
      31). The plasma and urine NO2 + NO3 levels were significantly higher in the
      untreated diabetic rats compared with the untreated normal rats before ischaemia
      (p < 0.001). The ischaemic acute renal failure in non-diabetic rats increased the
      plasma and urinary NO2 + NO3 excretion after ischaemia. The urinary excretion of
      these metabolites decreased significantly and their plasma levels remained
      unchanged in the ischaemic diabetic rats. The L-arginine administration resulted
      in a small but significantly higher creatinine clearance after clamping in the
      non-diabetic rats. The NO synthase inhibitor caused deterioration in renal
      function in all ischaemic and non-ischaemic groups. In summary, the greater
      vulnerability to ischaemia of the diabetic kidney seems to be associated with
      both impaired response to and impaired production of NO.

PMID- 8877287
TI  - Teratogenic effects of diabetes mellitus in the rat. Prevention by vitamin E.
AB  - We wanted to determine whether administration of vitamin E could reduce the
      production of free radicals which could play a role in the teratogenic effects of
      diabetes mellitus. Diabetes was induced in Wistar rats by the intravenous
      administration of streptozotocin. The animals were divided into six groups: one
      with no supplement (D) and two, supplemented during pregnancy either with oral
      vitamin E (150 mg/day) (D + E) or with a placebo (safflower oil) (D + O). Three
      other groups were kept under the same conditions, but were treated with insulin:
      D + I, D + I + E and D + I + O. There were three groups of matched controls: C, C
      + E and C + O. All animals were killed on day 11.5 of pregnancy. In C animals the
      percentages of reabsorptions and malformations were 1.3 and 2%, respectively,
      compared with 23.6, 24.3, 6.2 and 13.2%, respectively in D and D + I groups. The
      crown-rump length, number of somites, and protein and DNA content were higher in
      C animals than in the diabetic rats, independent of insulin treatment. When
      vitamin E was administered no changes in these parameters were observed in C and
      D + I animals; however, in the D mothers it reduced the rate of embryo
      malformations to 4.6% and increased the crown-rump length and the number of
      somites. However, vitamin E did not modify the protein and DNA content and the
      percentage of reabsorptions. In conclusion, administration of vitamin E to
      diabetic animals decreases the rate of embryo malformations and increases their
      size and maturation, supporting a role for free radicals in the teratogenic
      effects of diabetes.

PMID- 8877288
TI  - Comparison of the effects of ascorbyl gamma-linolenic acid and gamma-linolenic
      acid in the correction of neurovascular deficits in diabetic rats.
AB  - Essential fatty acid metabolism is impaired by diabetes mellitus and gamma
      linolenic acid rich treatments such as evening primrose oil correct deficits in
      nerve conduction and endoneurial blood flow in diabetic rats. Other
      mechanistically unrelated treatments, such as antioxidants and aldose reductase
      inhibitors have a similar effect and there may be positive interactions with
      multiple treatments. Our aim was to compare the efficacy of a novel essential
      fatty acid derivative, ascorbyl gamma-linolenic acid, with that of gamma
      linolenic acid in correcting diabetic neurovascular deficits. Eight weeks of
      diabetes caused 20.4 and 48.2% reductions in sciatic motor conduction velocity
      and nutritive endoneurial blood flow, respectively. Treatment was given for the
      last 2 weeks with gamma-linolenic acid (100 mg.kg-1.day-1) either in pure form or
      as ascorbyl gamma-linolenic acid, an equivalent dose of ascorbate (21 mg.kg-1.day
      1) or jointly with ascorbate and gamma-linolenic acid. Conduction velocity was
      corrected by 39.8, 87.4, 13.2 and 66.8% with gamma-linolenic acid, ascorbyl gamma
      linolenic acid, ascorbate and gamma-linolenic acid plus ascorbate, respectively.
      Corresponding ameliorations of the nutritive blood flow deficit were 44.0, 87.4,
      87.4, 13.2 and 65.7%. For the gamma-linolenic acid plus ascorbate combinatin, and
      especially for ascorbyl gamma-linolenic acid, the magnitude of correction for
      conduction velocity and blood flow was greater than expected for simple addition
      of ascorbate and gamma-linolenic acid, indicating a synergistic interaction.
      Thus, with an efficacy 40 times that of evening primrose oil in rats, ascorbyl
      gamma-linolenic acid may be a suitable candidate for clinical trials of diabetic
      neuropathy.

PMID- 8877284
TI  - The role of interleukin-1 in the pathogenesis of IDDM.

PMID- 8877289
TI  - Regulatory role of eicosanoids in extracellular matrix overproduction induced by
      long-term exposure to high glucose in cultured rat mesangial cells.
AB  - Accumulation of extracellular matrix in the mesangium and altered renal
      eicosanoid synthesis are two prominent features of diabetic glomerular disease.
      We investigated the relationship between eicosanoid and extracellular matrix
      production in rat mesangial cells cultured under high glucose vs normal glucose
      conditions. Long-term exposure of rat mesangial cells to high glucose, but not to
      iso-osmolar mannitol, significantly increased extracellular matrix accumulation
      and gene expression and transforming growth factor-beta (TGF-beta) mRNA levels,
      and decreased prostaglandin (PG) E2 synthesis without affecting production of
      either thromboxane (TX) B2 or PGF2 alpha, with respect to cells incubated in
      normal glucose. Addition of exogenous PGE2 resulted in a dose-dependent reduction
      of matrix protein and mRNA levels and TGF-beta gene expression in cells cultured
      in either normal or high glucose conditions, whereas exposure to exogenous PGF2
      alpha produced a significant increment in matrix production and matrix and TGF
      beta gene expression in cells grown in normal glucose, but only a slight increase
      in those cultured in high glucose. Stimulation of endogenous endoperoxide
      metabolism towards PGE2 and PGF2 alpha synthesis with FCE-22,178, a drug
      originally developed as TXA2 synthase inhibitor, resulted in a dose-dependent
      decrease in matrix accumulation and matrix and TGF-beta gene expression which was
      suppressed by coincubation with the cyclo-oxygenase inhibitor fenoprofen blocking
      the FCE-22,178-enhanced PG production. In both cell lines, the rate of synthesis
      of TXA2 was very low and the selective blockade of its synthesis (by two other
      TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor
      antagonist BM-13,177) did not alter matrix production or TGF-beta mRNA levels.
      These results suggest that the cyclo-oxygenase pathway is involved in the
      regulation of matrix changes induced by high glucose in rat mesangial cells; the
      reduced production of PGE2 may enhance the synthesis or potentiate the effect of
      stimulators of ECM formation such as TGF-beta, whereas TXA2 does not appear to be
      involved. These data also indicate that glucose-enhanced mesangial matrix
      accumulation may be prevented by exogenous PGE2 or by drugs capable of increasing
      endogenous PGE2 synthesis.

PMID- 8877291
TI  - Comparison of National Diabetes Data Group and World Health Organization criteria
      for detecting gestational diabetes mellitus.
AB  - We compared the criteria for diagnosis of gestational diabetes mellitus (GDM) of
      the National Diabetes Data Group (NDDG) and the World Health Organization (WHO)
      and studied the outcomes of pregnancy. A 50-g glucose screening test and 75-g
      oral glucose tolerance test (OGTT) were scheduled for 709 pregnant women in the
      same week between the 24th and 28th week of pregnancy. Blood glucose was measured
      1 h after the 50-g glucose screening test and if found to be 7.8 mmol/l or more,
      a 100-g OGTT was scheduled within 7 days after a 75-g OGTT. The prevalence of GDM
      was found to be 1.4% (10/709) and 15.7% (111/709) by NDDG and WHO criteria (2 h >
      or = 7.8 mmol/l), respectively. Using NDDG criteria, all the GDM patients had
      abnormal 75-g OGTT by WHO criteria. NDDG and WHO criteria were significantly
      different when compared with normal OGTT by each criteria for age, BMI, pregnancy
      induced hypertension, Caesarian delivery, macrosomia and neonatal hypoglycaemia.
      Of 14 women with macrosomic infants 6 had an abnormal WHO test while only 3 of 14
      had an abnormal NDDG test. These findings suggest that WHO criteria GDM patients
      had significantly worse outcomes of pregnancy and fewer perinatal complications
      were missed than with the more cumbersome NDDG criteria, and no case of GDM as
      diagnosed by NDDG criteria was missed.

PMID- 8877290
TI  - Epidemiology of childhood IDDM in Northern Ireland 1989-1994: low incidence in
      areas with highest population density and most household crowding. Northern
      Ireland Diabetes Study Group.
AB  - During the period 1989-1994, 462 cases of insulin-dependent diabetes mellitus
      were registered among children from Northern Ireland aged under 15 years. The
      estimated completeness of the register was 98.8% (95% confidence interval (CI)
      97.7%, 99.9%). A standardised rate of 19.6 (95% CI 17.8, 21.4) per 100 000 person
      years was obtained, placing Northern Ireland near the top of the range of
      published incidence in the United Kingdom, with a rate close to that reported for
      Scotland. In an analysis based on 217 postcode sectors, areas with a high
      population density and the most material deprivation were observed to have the
      lowest incidence rates. After inclusion of population density in a Poisson
      regression analysis, the component of deprivation which was found to be most
      significant was household crowding. Relative to children living in areas of low
      population density, there was a reduced risk for children in medium (relative
      incidence 0.85 (95% confidence limits CI 0.67, 1.09)) and high (0.62 (95% CI
      0.48,0.80)) population density areas. Similarly, relative to children living in
      areas with low levels of household crowding, there was a reduced risk for
      children in medium (relative incidence 0.73 (95% CI 0.58,0.93)) and high (0.67
      (95% CI 0.53, 0.83)) levels of household crowding. Tests for space-time
      clustering at diagnosis and at birth were negative. A possible explanation for
      the differences in incidence rate observed in this study is that exposure to
      infections very early in childhood is a protective factor. Later infections may
      act as either initiators or promoters of diabetes, but the absence of space-time
      clustering suggests that no single specific infectious agent is responsible.

PMID- 8877292
TI  - Effects of insulin and lipid emulsion on renal haemodynamics and renal sodium
      handling in IDDM patients.
AB  - To evaluate the role of insulin and hypertriglyceridaemia in the regulation of
      renal haemodynamics and sodium handling in insulin-dependent diabetes mellitus
      (IDDM), 11 IDDM patients without microalbuminuria and 13 weight-, age-, protein
      intake- and sex-matched healthy control subjects were studied. Clearances of
      inulin (Cin), para-amino-hippuric acid (CPAH), sodium (CNa), and lithium (CLi)
      were measured in four 60-min clearance periods (periods I, II, III and IV) during
      isoinsulinaemia with lipid emulsion infusion (study 1), a hyperinsulinaemic
      isoglycaemic clamp with Intralipid infusion (study 2), and during time-controlled
      isoinsulinaemia (study 3). We found that Cin, CPAH and filtration fraction were
      comparable in IDDM and control subjects, whereas CNa was decreased in diabetic
      subjects (2.01 +/- 1.11 vs 3.03 +/- 1.32 ml/min; p < 0.05) due to elevations of
      proximal tubular fractional and absolute reabsorptions of sodium (p < 0.05).
      Insulin infusion did not affect Cin, increased CPAH (p < 0.05) and, consequently,
      lowered the filtration fraction (p < 0.01) in both groups. While acute
      hyperinsulinaemia resulted in increases in distal tubular fractional and absolute
      reabsorptions of sodium (p < 0.01) contributing to a fall in CNa (p < 0.01) in
      control subjects, in diabetic subjects the sodium-retaining effect of insulin was
      not significant. The lipid emulsion did not alter any of the estimated
      parameters. We conclude that IDDM without microalbuminuria is associated with a
      tendency to sodium retention which is not aggravated by insulin when compared to
      control subjects. Acutely induced hypertriglyceridaemia does not alter renal
      haemodynamics or renal sodium handling.

PMID- 8877293
TI  - Interaction of sulphonylurea derivatives with vascular ATP-sensitive potassium
      channels in humans.
AB  - Cardiovascular adenosine-5'-triphosphate-sensitive potassium (KATP) channels have
      been reported to play an important role in endogenous cardioprotective
      mechanisms. Sulphonylurea derivatives can inhibit these cardioprotective
      mechanisms in animal models. We investigated whether therapeutic concentrations
      of sulphonylurea derivatives can block vascular KATP channels in humans. The
      forearm vasodilator responses to administration of the specific KATP channel
      opener diazoxide into the brachial artery of healthy male volunteers were
      recorded by venous occlusion plethysmography. This procedure was repeated with
      concomitant intraarterial infusion of:1) the sulphonylurea derivative
      glibenclamide (0.33 or 3.3 micrograms. min-1. dl-1, both n = 12), 2) the new
      sulphonylurea derivative glimepiride (2.5 micrograms.min-1. dl-1, n = 12) or 3)
      placebo (n = 12). The effects of glibenclamide on the vasodilator responses to
      sodium nitroprusside were also studied (n = 12). Glibenclamide significantly
      inhibited the diazoxide-induced increase in forearm blood flow ratio (ANOVA with
      repeated measures: p < 0.01). During the highest diazoxide dose this ratio (mean
      +/- SEM) was lowered from 892 +/- 165 to 449 +/- 105%, and from 1044 +/- 248 to
      663 +/- 114% by low- and high-dose glibenclamide, respectively. In contrast,
      neither glimepiride nor placebo attenuate diazoxide-induced vasodilation.
      Furthermore, glibenclamide did not affect nitroprusside-induced vasodilation. We
      conclude that therapeutic concentrations of the classical sulphonylurea
      derivative glibenclamide result in significant blockade of vascular KATP channels
      in humans. The newly developed glimepiride seems to be devoid of these
      properties.

PMID- 8877294
TI  - Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase
      (GAD65) autoantibodies in childhood IDDM.
AB  - The prevalence and titre of epitope-specific autoantibodies to glutamic acid
      decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65
      antibody (Ab)-positive healthy children were determined using four GAD65/67
      chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C
      terminal (C) epitopes of GAD65. Radioligand binding assays for IgGAb used
      immunoprecipitation of in vitro translated 35S-GAD. We found autoantibodies to
      GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p < 0.0001) and to the
      GAD65-N-67 chimaera in 25 of 155 (16%) (p < 0.0001) IDDM sera. GAD67Ab were found
      almost exclusively (17 of 19, 89%) in GAD65Ab-positive sera and the levels of
      GAD67Ab correlated with those of GAD65Ab (r2 = 0.5913; p = 0.009). GAD65Ab
      directed to GAD65-M were found in 104 of 155 (67%), to GAD65-C in 104 of 155
      (67%) and to GAD65-M + C in 116 of 155 (75%) of IDDM sera, and indicated
      reactivity to at least two distinct epitopes. Among the nine GAD65Ab-positive
      healthy children, two (22%) were also positive with GAD67, nine (100%) with GAD65
      M + C, seven (78%) with GAD65-M, eight (89%) with GAD65-C and two (22%) with
      GAD65-N-67. Titres of GAD65Ab (p = 0.007), GAD65-C-Ab (p = 0.002) and GAD65-C + M
      Ab (p = 0.003), but not of GAD65-M-Ab (p = 0.101) were significantly higher in
      IDDM than in healthy children. We conclude that GAD65Ab in IDDM and healthy
      children are directed to middle and C-terminal epitopes, and propose that levels
      of antibodies specifically directed to the carboxy-terminal end of GAD65 may
      distinguish IDDM from healthy children.

PMID- 8877295
TI  - Failure to adequately adapt reduced insulin sensitivity with increased insulin
      secretion in women with impaired glucose tolerance.
AB  - To study the islet adaptation to reduced insulin sensitivity in normal and
      glucose intolerant post-menopausal women, we performed a euglycaemic,
      hyperinsulinaemic clamp in 108 randomly selected women, aged 58-59 years. Of the
      20 women with the lowest insulin sensitivity, 11 had impaired glucose tolerance
      (IGT) whereas 9 had normal glucose tolerance (NGT). These women together with 15
      women with medium insulin sensitivity and 16 women with high insulin sensitivity
      and NGT were further examined with arginine stimulation at three glucose levels
      (fasting, 14 and > 25 mmol/l). In NGT, the acute insulin response (AIR) to 5 g
      i.v. arginine at all three glucose levels and the slopeAIR, i.e. the glucose
      potentiation of insulin secretion, were markedly increased in the women with the
      lowest insulin sensitivity and NGT compared to those with medium or high insulin
      sensitivity. In contrast, in low insulin sensitivity, AIR was significantly lower
      in IGT than in NGT (at glucose 14 mmol/l p = 0.015, and at > 25 mmol/l p =
      0.048). The potentiation of AIR induced by low insulin sensitivity in women with
      NGT was reduced by 74% (AIR at 14 mmol/l glucose) and 57% (AIR at > 25 mmol/l
      glucose), respectively, in women with IGT. Also the slopeAIR was lower in IGT
      than in NGT (p = 0.025); the increase in slope AIR due to low insulin sensitivity
      was abolished in IGT. In contrast, glucagon secretion was not different between
      women with IGT as opposed to NGT. We conclude that as long as there is an
      adequate beta-cell adaptation to low insulin sensitivity with increased insulin
      secretory capacity and glucose potentiation of insulin secretion, NGT persists.

PMID- 8877296
TI  - Examination of two genetic polymorphisms within the renin-angiotensin system: no
      evidence for an association with nephropathy in IDDM.
AB  - Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM)
      patients who develop diabetic nephropathy. Genetic polymorphism within the renin
      angiotensin system has been implicated in the aetiology of a number of
      cardiovascular disorders; these loci are therefore candidate genes for
      susceptibility to diabetic renal disease. We have examined the angiotensin
      converting enzyme insertion/deletion polymorphism and angiotensinogen methionine
      235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and
      diabetic nephropathy. Patients were classified as having nephropathy by the
      presence of persistent dipstick positive proteinuria (in the absence of other
      causes), retinopathy and hypertension (n = 242). Three groups were examined for
      comparison: ethnically matched non-diabetic subjects (n = 187); a geographically
      defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients
      with long duration of disease (> 15 years) and no evidence of overt nephropathy
      (n = 166). No significant difference was seen in distribution of angiotensin
      converting enzyme or angiotensinogen genotypes between IDDM patients with
      nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584,
      respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701
      and 0.190, respectively). We conclude that these genetic loci are unlikely to
      influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.

PMID- 8877297
TI  - Association of aldehyde dehydrogenase with inheritance of NIDDM.
AB  - To investigate the influence of the mitochondrial aldehyde dehydrogenase 2
      (ALDH2) genotype on the clinical features of diabetes, 212 Japanese patients with
      non-insulin-dependent diabetes mellitus (NIDDM) (154 males and 58 females aged 17
      83 years; mean age 58.2 years) were investigated. Genotyping of ALDH2 was
      performed by the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method. The pattern of inheritance of diabetes and
      various clinical parameters was compared between active and inactive ALDH2
      groups. Of the 212 subjects, 120 had active ALDH2 and 92 had inactive ALDH2. The
      percentage of patients with a diabetic mother was higher in the inactive ALDH2
      group (32.6%) than in the active ALDH2 group (19.2%) (p < 0.05). The prevalence
      of proliferative retinopathy was lower in the inactive ALDH2 group than in the
      active ALDH2 group (p < 0.05). However, other clinical parameters showed no
      difference. We conclude that maternal inheritance of diabetes was common in the
      inactive ALDH2 group. The finding is suggestive of a relationship between alcohol
      intolerance and inheritance of diabetes. We speculate that the interaction
      between mitochondrial DNA and ALDH2 inactivity causes an increase of
      mitochondrial DNA mutations or deletions, thereby inducing the maternal
      inheritance of diabetes. The relationship of the ALDH2 genotype with
      proliferative retinopathy is interesting, because it resembles that of
      chlorpropamide alcohol flushing with severe diabetic retinopathy. The interaction
      of aldehyde dehydrogenase isoenzymes might have an aetiological role, since
      aldehyde dehydrogenase 1 plays an important part in oxidation of retinal to
      retinoic acid. However, the number of affected patients with proliferative
      retinopathy was small, hence, our result should be considered as a preliminary
      finding.

PMID- 8877298
TI  - Insulin resistance as a programmed response to fetal undernutrition.

PMID- 8877299
TI  - Lifelong consequences of metabolic adaptations in utero?
AB  - Dr. Phillips argues that insulin resistance in adult life may be the price the
      developing fetus has to pay in return for a short-term successful adaptation to
      undernutrition in utero. The concept is interesting, and, indeed, challenging.
      There is, however, a strong need for expansion of the existing knowledge of the
      possible developmental mechanisms involved, especially against the background of
      the obvious diagnostic and therapeutic gains in this particular group of
      patients.

PMID- 8877300
TI  - Influences of the intrauterine metabolic environment on adult disease: what may
      we infer from size at birth?

PMID- 8877301
TI  - European Dimension of Diabetes Research.

PMID- 8877302
TI  - Outcomes of assistive technology use on quality of life.
AB  - The results from many research efforts on the use of assistive devices are
      reviewed and summarized. Further, conceptual and methodological issues related to
      the use and abandonment of assistive technologies are discussed. Overall, this
      review should be helpful to professionals making device recommendations,
      documenting the need for a device, and assessing short- and long-term device
      utilization. The available literature lends support to a model of matching person
      and technology that considers environments of device use, characteristics of the
      user's preferences and expectations, and device features and functions. To ensure
      that assistive technologies enhance users' quality of life, future emphases
      should focus on consumer involvement in the selection and evaluation of
      appropriate assistive technology, and ways to make technologies more widely
      available and affordable.

PMID- 8877303
TI  - Relationship between occupation and life satisfaction in people with multiple
      sclerosis.
AB  - Activity is essential for all human beings, and provides a means through which
      human beings develop, gain recognition, and fulfil life's goals. The focus for
      this study was on activities performed by people with a chronic disease and their
      effects on experienced life satisfaction. Thirty subjects with multiple sclerosis
      (MS) were interviewed with regard to activities of daily living (ADL), and
      checklists were used for activity preferences and levels of satisfaction with
      life as a whole and with nine domain-specific forms of life satisfaction. The
      results of the study reveal 14 of the subjects to be satisfied and 16 to be
      dissatisfied. The main differences between the two groups were that the satisfied
      were less tired, and that they were more independent in self-care. Those in the
      satisfied group reported being more satisfied with leisure situation (57%, cf.
      25% in the dissatisfied group) and housekeeping ability (36%, cf. 6% in the
      dissatisfied group). Leisure and housekeeping appear to have an impact on
      subjects' experienced satisfaction, and are factors to be taken into
      consideration by occupational therapists when treating MS patients.

PMID- 8877304
TI  - The Frenchay Activities Index in stroke patients: agreement between scores by
      patients and by relatives.
AB  - The aim of the study was to compare stroke patients' own scorings of the Frenchay
      Activities Index with scorings based on interviews with their nearest relatives.
      Fifty-two patients and relatives were interviewed separately 1 year after the
      stroke. The mean sumscore based upon information from the patients was 29.0, and
      that based upon the relatives' replies was 27.7 (mean difference 1.4, 95%
      confidence interval (CI) -0.1 to 2.8). The Kendall tau B correlation between the
      two sumscores was 0.72 (95% CI 0.63 to 0.81). In half of the patients the two
      sumscores differed by four points or more, and in every fourth the two sumscores
      differed by six points or more. The weighted kappa for the single items varied
      between 0.36 and 0.89. No characteristics of patients or relatives were
      identified that were related to disagreement between the two scores.

PMID- 8877305
TI  - The 'PRESTON Profile'--the first disease-specific tool for assessing quality of
      life in patients with malignant glioma.
AB  - This study seeks to assess the quality of life in patients with malignant glioma,
      using as its measuring tool the disease-specific "PRESTON Profile' designed by
      the author. Twenty patients took part in the project. Following completion of the
      questionnaire, semi-structured interviews were conducted with each subject to
      further explore issues raised by their responses to the "PRESTON Profile'.
      Results showed that the "PRESTON Profile' was perceived as a most pertinent tool
      for ascertaining quality of life in patients with malignant glioma. However, it
      was apparent that a questionnaire alone is not the ideal way of assessing quality
      of life in these patients, as the concentration required to reach each statement,
      and then to make a considered decision, sometimes proved too demanding.
      Interviewing patients (alone or with their spouse/carer)- utilizing information
      gained from their responses to the "PRESTON Profile' elicited considerably more
      information. Thus the "PRESTON Profile' can be used successfully as both an
      assessment of quality of life, and as a "launching pad' for more in-depth
      counselling, for patients with malignant glioma.

PMID- 8877306
TI  - Dynamic and static physical training in patients with rheumatoid arthritis:
      application of a self-appraisal and coping model.
AB  - A self-appraisal and coping model was examined using a longitudinal data set
      involving 56 classical or definite rheumatic arthritis patients randomly assigned
      to either dynamic (n = 28) or static (n = 28) physiotherapeutic training. The
      model considers both adaptational consequences and antecedents of training
      (muscular endurance, pain, self-appraisal, and coping through avoidance or
      painful problem-solving). Measures were obtained prior to and after a 6-week
      training period (partly supervised and partly self-training) at a health-care
      centre, and after an additional 3 months of self-training only. Path analysis
      supported the mediating role of self-appraisal and of avoidance in influencing
      muscular endurance in dynamic training patients. Regression analyses likewise
      supported these conclusions, suggesting some patients in dynamic training to be
      caught in a vicious circle of avoidance and low self-appraisal. Theoretical
      issues are discussed, and suggestions made for developing more effective
      interventions in rheumatic patients.

PMID- 8877307
TI  - A community-oriented programme for rehabilitation of persons with arthritis.
AB  - A community-oriented programme for rehabilitation of persons with arthritis is
      described. It combines an 8-week ambulatory rehabilitation course (including
      patient education) at a rehabilitation institution, with long-term self
      rehabilitation (at patients' homes), supervised by primary-care nurses. Sixty
      persons (mean age 54; 80% females) with a 13-year average duration of arthritis,
      were suffering pain, physical limitations, difficulties in social activities,
      tension and a tendency to depression. They had completed the course and a 12
      month self-rehabilitation at home, and were assessed with the Arthritis Impact
      Measurement Scales (AIMS) questionnaire on admission to the course, at its
      completion and 1 year thereafter. Assessment upon completion of the course showed
      improvement in all areas studied. Measurements at follow-up showed that the
      majority carried out self-rehabilitation activities and preserved the improved
      functional status. The programme provided a much-needed service to arthritis
      sufferers living in the community, and promoted both the reorientation of
      institution-based rehabilitation professionals towards the community and self
      rehabilitation and the cooperation between the institution and primary care.

PMID- 8877308
TI  - Traumatic mutism in severe head injury relieved by oral diazepam.
AB  - A 34-year-old woman with a severe closed-head injury had many impairments
      including apparent global aphasia. After a diazepam premedication for a motor
      point block she was heard to speak a few words. A trial of oral diazepam
      succeeded in restoring speech adequate to make her needs known, which persisted
      on a maintenance dose of 5 mg t.d.s. The possible diagnoses and reasons for this
      phenomenon are discussed. We suggest that diazepam may be useful in assessing
      speech in selected people with severe head injuries.

PMID- 8877309
TI  - Potential of opioid antagonists in the treatment of levodopa-induced dyskinesias
      in Parkinson's disease.
AB  - Current treatments for Parkinson's disease (PD) rely on dopamine-replacing
      strategies, and centre around dopamine precursors (e.g. levodopa) or directly
      acting dopamine agonists. With long-term therapy these agents lose much of their
      clinical utility due to the appearance of adverse effects such as dyskinesias
      and/or a wearing off of efficacy. Although dyskinesias in Huntington's disease,
      hemiballism and experimental animals are thought to be associated with reductions
      in amino acid transmission within the lateral and medial segments of the globus
      pallidus, the neural mechanisms underlying treatment-related dyskinesias in PD
      are poorly understood. Recent evidence suggests that, within these regions of the
      brain, the opioid peptides enkephalin and dynorphin, acting at delta and kappa
      opioid receptors, respectively, can reduce the release of amino acid
      transmitters. Furthermore, the synthesis of these peptides appears to be enhanced
      in neurons projecting to the pallidal complex in animal models of PD following
      repeated treatment with dopamine-replacing agents that also cause dyskinetic
      adverse effects (e.g. levodopa and apomorphine). In contrast, dopamine receptor
      agonists such as bromocriptine and lisuride do not cause dyskinetic adverse
      effects following long-term treatment, and do not elevate peptide synthesis when
      given de novo. These data, together with recent data on the behavioural effects
      of opioid antagonists in a rodent model of levodopa-induced dyskinesia in PD,
      suggest the possibility that antagonists of opioid receptors may prove useful as
      adjuncts to levodopa. By limiting the severity of dyskinetic adverse effects,
      these drugs may help extend the time for which the antiparkinsonian effects of
      such compounds can be usefully exploited.

PMID- 8877310
TI  - Early detection of Parkinson's disease. Implications for treatment.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      worldwide and is characterised by cardinal clinical features and specific
      pathological findings. It is possible to detect PD early on in the course of the
      disease, and certain laboratory studies may identify preclinical stages. Based on
      this information, and the hypothesis that there is a long preclinical period,
      there appears to be a window of opportunity to influence the natural course of
      the disease. Postulates regarding pathogenesis, such as oxidative stress and
      excitotoxicity, have led to the discovery of abnormal mitochondrial function in
      PD and a search for biochemical markers. Functional imaging studies have detected
      subclinical nigral dopaminergic dysfunction in individuals at risk of developing
      PD. Current symptomatic therapies are aimed at enhancing dopaminergic
      transmission. However, some commonly used PD medications may have alternative
      actions with both symptomatic and neuroprotective consequences. Bromocriptine has
      been postulated to have antioxidant effects and amantadine to have N-methyl-D
      aspartate (NMDA) receptor antagonistic properties. Both have been reported to be
      associated with improved survival in PD. Additionally, monoamine oxidase type B
      inhibitors may provide neuroprotection. Recent new medications are also under
      study with regard to neuroprotection. Despite these advances, until there is a
      better understanding of the aetiology and pathogenesis of PD, there will be no
      definitive long-term benefit of early diagnosis and treatment of PD.

PMID- 8877312
TI  - Adjuvant therapy in breast cancer. Optimal use in the elderly.
AB  - Breast conservation surgery may replace mastectomy in patients with small,
      localised breast tumours of up to 4 cm in diameter. Clear surgical margins
      (microscopically defined) are desirable. Radiotherapy to the conserved breast is
      recommended for all patients, although it may be relatively safe to withhold it
      in some better-risk T1 patients. This decision must frequently be taken in the
      elderly and infirm. Adjuvant tamoxifen has an established place in the systemic
      management of all elderly patients with invasive breast cancer. In contrast,
      adjuvant chemotherapy has no established role in the elderly.

PMID- 8877311
TI  - New directions in the drug treatment of Parkinson's disease.
AB  - Parkinson's disease, a clinical syndrome with 4 cardinal features (bradykinesia,
      resting tremor, increased muscular rigidity and impaired postural balance), is
      mainly caused by the loss of dopaminergic neurons in the substantia nigra pars
      compacta. Although levodopa remains the 'gold standard' in the treatment of the
      disease, several emerging strategies are currently being developed. The first
      concerns new symptomatic drugs that either potentiate the effects of levodopa
      (e.g. slow-release preparations of levodopa, catechol-O-methyltransferase
      inhibitors and new dopamine agonists) or target clinical symptoms resistant to
      dopaminergic drugs (e.g. glutamate antagonists). The second strategy is to find
      drugs that are able to prevent or delay the neuronal death observed in
      Parkinson's disease. Several neuroprotective drugs are now in development in
      experimental research, but clinical trials in this area are still lacking. The
      development of these new drugs also depends on the validation of new clinical
      methodologies.

PMID- 8877313
TI  - Optimal management of anxiety in older patients.
AB  - Although the incidence of anxiety disorders diminishes with age, the prevalence
      of anxiety symptoms among older patients is substantial. These symptoms, which
      include cognitive and somatic manifestations, are a source of diminished quality
      of life. The many potential sources of illness- and medication-induced anxiety
      must be excluded before instituting treatment. The general principles of
      antianxiety medication treatment in older patients include: (i) symptom relief
      with minimum sedation; (ii) improvement in sleep; (iii) freedom from autonomic
      and cognitive toxicities; and (iv) freedom from physical dependence and drug
      interactions. Older compounds such as the tricyclic antidepressants should be
      avoided, since more modern agents (e.g. benzodiazepines and buspirone) are well
      tolerated and effective. Modern antidepressants have also been used to reduce
      anxiety symptoms, although there is a potential for the opposite effect to occur.
      The selective serotonin reuptake inhibitors appear to be better suited to
      treating syndromes such as panic and obsessive-compulsive disorder, whereas
      nefazodone would be a better choice for generalised anxiety complicated by
      depression.

PMID- 8877315
TI  - Unoprostone (isopropyl unoprostone)
AB  - Unoprostone (isopropyl unoprostone) is a docosanoid compound which is related to
      a metabolite of prostaglandin (PG)F2 alpha. Unoprostone has oculo-hypotensive
      effects. The drug is thought to lower intraocular pressure (IOP) by increasing
      aqueous humour outflow. Aqueous humour production remains unaffected. Marked
      reductions in IOP have been demonstrated in healthy volunteers and patients with
      glaucoma or ocular hypertension after instillation of unoprostone 0.12%.
      Unoprostone 0.12% appears to have similar efficacy to timolol 0.5% in patients
      with primary open-angle glaucoma or ocular hypertension. In phase II and III
      clinical studies, adverse events observed with unoprostone were predominantly
      local; systemic effects occurred less frequently.

PMID- 8877314
TI  - Amylin, amyloid and age-related disease.
AB  - Amylin, a 37-amino acid peptide, is cosecreted with insulin from the beta-cells
      of the pancreatic islets in normal response to physiological stimuli. It is the
      major protein of islet amyloid, which is usually present in the pancreases of
      people with non-insulin-dependent (type II) diabetes mellitus. Amylin elicits
      potent effects on carbohydrate metabolism in rodent tissues, causing insulin
      resistance in skeletal muscle and liver. A close structural relationship exists
      between amylin and the 2 calcitonin gene-related peptides, which are widely
      distributed neuropeptides and potent vasodilators. These exert biological effects
      similar to those of amylin on the organs primarily responsible for the regulation
      of carbohydrate metabolism. All 3 peptides are thought to cause their biological
      actions by binding to similar cell surface receptors. This article reviews the
      field of amylin and its role in the physiological regulation of carbohydrate
      metabolism, and in disease mechanisms associated with insulin resistance in
      diabetes mellitus, impaired glucose tolerance and essential hypertension.
      Potential therapeutic applications are also discussed.

PMID- 8877316
TI  - Scapuloperoneal muscular atrophy: Davidenkow's syndrome. Family report.
AB  - The nosology of scapuloperoneal syndrome remains controversial. Is it a variant
      of Charcot-Marie-Tooth's disease, a form of myopathy, or of spinal muscular
      atrophy is still unknown. A family with a scapuloperoneal syndrome caused by
      anterior horn cell involvement is described. Data for sensory involvement were
      also found. In addition one member of the family had motor nerves and
      corticospinal tract involvement. The distribution of weakness and muscle wasting
      was unusual--only lower limbs were involved. However, electromyographic data for
      both upper and lower limbs involvement were evident. The combination of
      scapuloperoneal syndrome with sensory loss has been described by Davidenkow, but
      was not proved by neurographic investigation. Later only one case with proved
      sensory disturbances was reported. Patients with motor nerves involvement in
      addition were reported, but not received satisfactory explanation. Probably in
      some patients the disease could be manifested only with anterior horn cell
      involvement, while in other both motor and sensory nerves could be involved. In
      conclusion we suppose that the scapuloperoneal muscular atrophy is a form of
      spinal muscular atrophy which could be manifested by different symptoms.

PMID- 8877317
TI  - Application of the method of spectral-statistical analysis EMG for evaluating the
      influence of medication on the treatment of Parkinson's disease.
AB  - The results of using of the new method analysis EMG in the evaluation of the
      influence of single pharmacological tests (PhT) for Parkinson's disease are
      described in this article. PhT applied for investigation of the group 41 patients
      diagnosed with Parkinson's disease of different etiologies, forms and stages. The
      study was carried out before taking the medicine and 40-60 minutes after taking
      the medicine. Patients were prescribed a single, habitual, individualized doses
      of anti-Parkinson's medicine. Analysis of the materials show that in the PhT, in
      23% of the cases, for the group of muscles under study change in the tremor
      frequency in the direction of normality was observed. In 2% of the cases,
      reduction in the magnitude of tremor was observed. In 10% of the cases, both
      frequency and magnitude of tremors were registered. In 65% of the cases, no
      change what soever was indicated. For those patients for which the effectiveness
      of the medicine was manifested independently in certain groups of muscles,
      corrective medical therapy was recommended.

PMID- 8877318
TI  - Changes of motor evoked potential amplitudes following magnetic stimulation after
      hyperventilation.
AB  - The influence of hyperventilation on amplitudes of motor evoked potentials (MEP)
      following cortical and root magnetic stimulations was tested in ten healthy
      volunteers. Hyperventilation significantly increased MEP amplitude following
      cortical stimulation (p < 0.01) but failed to change MEP amplitude following root
      stimulation. This finding is compatible with the concept of hyperventilation as a
      promoter of greater excitability at the level of cortical structures. The
      provoking method applied during magnetic cortical stimulation might be a useful
      procedure in studying some functional affections associated with
      hyperventilation, such as hyperventilation tetany or panic disorder.

PMID- 8877319
TI  - Abnormalities in motor conduction in vitamin B12 deficiency.
AB  - Three patients with vitamin B12 deficiency were studied to determine the extent
      of the disturbance of nerve conduction. All had small or absent sural potential
      and in addition all had some abnormalities of F response. Motor nerve conduction
      in legs was borderline or abnormal and in two patients there were some features
      of a mononeuritis multiplex syndrome. Abnormalities of motor conduction are thus
      part of the changes in vitamin B12 deficiency in addition to the involvement of
      the sensory nerves.

PMID- 8877320
TI  - Comparison of sensory mid-palm studies to other techniques in carpal tunnel
      syndrome.
AB  - This prospective study was done to assess a technique of comparing Median-Ulnar
      sensory latency differences across the wrist (Sensory Palm [M-U]) to diagnose
      carpal tunnel syndrome (CTS) and to compare the relative sensitivities of other
      previously reported techniques: Median-Radial sensory difference (Sensory Thumb
      [M-R]), Median-Ulnar mixed palm difference (Mix Palm [M-U]) and Median-Ulnar
      sensory digit difference (Sensory Digits [M-U]). 90 Hands met the
      electrodiagnostic (EDX) criteria for mild CTS. The Sensory Thumb (M-R) was
      abnormal in 90% of the hands followed in order by Mix Palm (M-U) 61%, Sensory
      Digits (M-U) 42% and Sensory Palm (M-U) 33%. All differences were statistically
      significant (p < .01). Sensory Palm (M-U) did not significantly add to the
      diagnosis of CTS. The Sensory Thumb (M-R) was relatively the most sensitive
      followed by Mix Palm (M-R) was relatively the most sensitive followed by Mix Palm
      (M-U), Sensory Digits (M-U) and Sensory Palm (M-U).

PMID- 8877321
TI  - Early onset cerebellar ataxia with retained tendon reflexes (EOCA): an
      electromyographic study.
AB  - This prospective study was undertaken to characterize better
      electrophysiologically the newly described clinical entity of "Early onset
      cerebellar ataxia with retained tendon reflexes (EOCA)" and compare it with
      Olivopontocerebellar atrophy (OPCA) and Friedreich's ataxia (FA). Concentric
      needle electromyography and motor (median, common peroneal and posterior tibial)
      and sensory (median, sural and posterior tibial) nerve conduction studies were
      carried out in 14 patients of EOCA. The results were compared with those of 10
      and 16 patients of FA and OPCA respectively. All patients of EOCA had either
      motor or sensory conduction abnormalities, motor being slightly more frequent
      than sensory (87.7% versus 78.6%). The neuropathy was distal and symmetrical,
      lacked correlation with duration or clinical stage of the disease, even between
      patients of the same family. Electrophysiological studies helped to detect
      subclinical motor and sensory neuropathy in most of the patients. No
      characteristic electrophysiologic abnormalities separated patients of EOCA from
      those of OPCA or FA, though the overall incidence of abnormalities was higher in
      the latter two groups. It is concluded that subclinical peripheral neuropathy is
      often present in patients of EOCA. The impaired proprioceptive sensation noted
      among these patients may be due to large fiber neuropathy rather than posterior
      column involvement alone. A subgroup of them, who have severe sensory neuropathy,
      may be difficult to differentiate clinically from patients of FA. The clinical
      entity of EOCA is indistinguishable electrophysiologically from FA and OPCA.

PMID- 8877322
TI  - Reciprocal inhibition in the forearm during voluntary contraction and thinking
      about movement.
AB  - The regulatory mechanism for the interaction of agonist and antagonist muscles is
      not still clear. In these studies we investigated reciprocal inhibition during
      voluntary contraction and thinking about movement by using transcranial magnetic
      stimulation (TMS) and the H reflex technique. Magnetic stimuli, with intensities
      10% above threshold, were delivered at the scalp under 3 experimental conditions;
      at rest, during voluntary isometric weak contraction and during thinking about
      movement. Surface EMG responses were taken from extensor carpi radialis (ECR) and
      flexor carpi radialis (FCR) muscles in 14 normal subjects. Inhibitions of
      antagonist muscles induced by thinking about agonist movement occurred in 8 ECR
      and 10 FCR muscles, but most of them were not statistically significant. H
      reflexes were obtained from the FCR muscles in 10 normal subjects under the same
      conditions. Voluntary wrist extension and thinking about wrist extension produced
      inhibition of the H reflex in the FCR muscles. Reciprocal inhibition of
      antagonist muscles may occur at the cortical and spinal cord levels. The
      excitability of motoneurons has effects on the H reflex amplitude. Motor evoked
      potential (MEP) response to TMS might be affected by the combination of input
      from the motor cortex and the spinal cord. TMS may evoke simultaneous
      facilitatory and inhibitory volleys to antagonist muscles. This may explain why
      the inhibitions in the TMS study were weaker than those in the H reflex study.

PMID- 8877323
TI  - Clinical usefulness of electrically elicited pain-related evoked potentials.
AB  - In 14 patients with sensory disturbance, the clinical usefulness of electrical
      pain-related evoked potentials (EPREPs) were studied. In four patients with deep
      sensation disturbance, conventional somatosensory evoked potentials (SEPs) were
      abnormal. However, EPREPs were abnormal only in one of the patients. In nine
      patients with pain-temperature sensation disturbance, SEPs were normal except for
      only one patient and EPREPs were abnormal in seven of the nine patients. In a
      patient with herpes zoster myelitis, EPREPs elicited by electrical stimulation
      below the disturbed spinal level were delayed. After symptomatic improvement,
      EPREPs recovered. EPREPs are useful in the clinical field.

PMID- 8877324
TI  - The effects of age, height and gender on the somatosensory evoked potentials in
      man.
AB  - Somatosensory evoked potentials (SEPs) reflect the activity of somatosensory
      pathways mediated through the dorsal columns of the spinal cord and the specific
      somatosensory cortex. In this study we aimed to demonstrate the effects of
      physiologic parameters such as height, age and gender on N9, N13, N20 SEP
      components and the central conduction time (CCT) to median nerve stimulation in
      Turkish population. The results revealed a statistically significant correlation
      between height, gender and SEP latencies (p < 0.05 and p < 0.0005 respectively)
      whereas no significant age related changes was found in SEPs. In all groups CCT
      was not influenced by these parameters.

PMID- 8877325
TI  - Fasciculation frequency changes at different length of relaxed muscle.
AB  - We have studied, in chronically denervated muscles, fasciculation potentials
      (FPs) which were clearly identified when the muscles were either relaxed or
      passively stretched. The frequency of 10 FPs was determined in both positions in
      seven patients. In stretched muscles, two FPs were no longer recorded, and the
      mean FP frequency decreased significantly (P < .01). There was also a decrease of
      the FP amplitude. As FPs are frequently associated with ordinary muscle cramps,
      stretching of the muscle may lessen the frequency of FPs by the same mechanism
      which stops cramps.

PMID- 8877326
TI  - Developing an integrated epidemiologic approach to emerging infectious diseases.

PMID- 8877327
TI  - Impact of technology on the emergence of infectious diseases.
AB  - Not all new threats from microorganisms result from changes within the
      microorganisms themselves. Innovative, progressive changes introduced by humans
      can provide advantages to microbes which, in turn, threaten the population. In
      most cases, advantages are provided unwittingly as a by-product of technology,
      and can be corrected when the problem is recognized. An end to progress is
      neither a practical nor desirable solution. Alertness (i.e., surveillance) for
      the emergence of new diseases and to changes in disease patterns will continue to
      be critical to ensure timely implementation of public health measures.

PMID- 8877328
TI  - Child-care practices: effects of social change on the epidemiology of infectious
      diseases and antibiotic resistance.
AB  - The increasing number of mothers of young children in the work force and the
      resultant escalated use of child-care facilities has had a marked effect on the
      epidemiology of infectious diseases in young children. Children attending child
      care are at high risk for respiratory and gastrointestinal tract illnesses. The
      high prevalence of infectious diseases in the child-care setting is accompanied
      by high usage of antibiotics, which in turn has resulted in spread of antibiotic
      resistant organisms. The infectious disease standards of the American Public
      Health Association/American Academy of Pediatrics guidelines were developed to
      prevent and limit transmission of infectious diseases in the child-care setting.
      Adherence to these standards is essential but will not completely eliminate the
      increased risk of infectious diseases in child-care settings. New challenges need
      to be addressed to assure that optimal health promotion and disease prevention is
      practiced in child-care settings. We approach the 21st century with a vast amount
      of medical knowledge, molecular technology, highly effective vaccines, and
      powerful antimicrobial agents. However, at the same time we face many unsolved
      serious problems, such as preventing or controlling the emergence and spread of
      antibiotic-resistant organisms that adversely affect our ability to treat
      infectious diseases. Further research is needed concerning the relations between
      child care, the use of antibiotics, and transmission of antibiotic-resistant
      organisms in order to design and implement the most effective strategies for
      preventing or controlling antibiotic resistance. The potential risk for
      transmission of HIV in the child-care setting also needs to be recognized, and
      procedures to prevent transmission of blood-borne pathogens need to be followed.
      Monitoring compliance with national standards for child-care facilities,
      dissemination of information concerning infectious diseases and use of
      antibiotics, and development and use of new vaccines are strategies which should
      be used to help protect the health of children in child-care environments.

PMID- 8877329
TI  - Emerging foodborne pathogens: Escherichia coli O157:H7 as a model of entry of a
      new pathogen into the food supply of the developed world.
AB  - There would appear to be little argument that the large outbreaks of E. coli
      O157:H7 which have occurred since the early 1980s represent a distinct, new
      phenomenon. The number of reported cases have increased dramatically, starting
      from zero in 1981; however, it is also clear that this increase in reported cases
      is in part an artifact of improved surveillance and reporting. Available data
      suggest that E. coli O157:H7 infections were present prior to 1982, although
      numbers appear to have been small. At a molecular level, the organism shows
      evidence of clonal origin, but there is not the striking clonality, with
      virtually identical pulsed-field gel electrophoresis and ribotyping patterns,
      which has been seen in situations such as the emergence of Vibrio cholerae O139
      Bengal in the Indian subcontinent in 1992 or the introduction of V. cholerae O1
      into naive populations in South America in 1991 (127-129). Findings are more
      consistent with the image of an organism which arose from a common ancestor, but
      which has had time to become distributed geographically and to show some evidence
      of genetic divergence. While this is an "emerging" infection, at least in terms
      of its distribution and public recognition, it is unlikely that it will be
      possible to identify the "first" O157:H7 case or to track the clonal spread of
      the organism through cattle or human populations.

PMID- 8877330
TI  - Tuberculosis control: the relevance of classic principles in an era of acquired
      immunodeficiency syndrome and multidrug resistance.

PMID- 8877331
TI  - Emerging infections: pandemic influenza.

PMID- 8877332
TI  - Malaria as a reemerging disease.

PMID- 8877333
TI  - Molecular epidemiology: applications of nucleic acid amplification and sequence
      analysis.

PMID- 8877334
TI  - Interaction of oxidized low density lipoprotein with macrophages in
      atherosclerosis, and the antiatherogenicity of antioxidants.
AB  - Macrophage cholesterol accumulation and foam cell formation, the hallmark of
      early atherosclerosis, is the result of enhanced cellular uptake of plasma low
      density lipoprotein (LDL). Native LDL, has to undergo oxidative modifications in
      order to be taken up at an enhanced rate by macrophages, leading to foam cell
      formation. Macrophage uptake of oxidized LDL involves its binding to scavanger
      receptors (including cellular proteoglycans) and this is followed by an impaired
      cellular cholesterol metabolism. Cells of the arterial wall including macrophages
      can oxidize LDL in a process that involves activation of cellular oxygenases,
      such as NADPH oxidase and 15-lipoxygenase. This process, however, also depends on
      the macrophage antioxidant environment, where glutathione peroxidase and reduced
      glutathione play an important protective role against cell-mediated oxidation of
      LDL. Macrophage phospholipids peroxidation under oxidative stress can also
      contribute to macrophage-mediated oxidation of LDL. Evidence for the occurrence
      of oxidized LDL in vivo is as follows: 1) In the atherosclerotic lesion [in
      humans, as well as in the transgenic, apolipoprotein E-deficient mice], LDL is
      oxidized (and as a result, it is also aggregated), in comparison to plasma LDL
      which is normally not oxidized. 2) Plasma LDL from patients at high risk for
      atherosclerosis (such as hypercholesterolaemic, hypertensive, diabetic and renal
      failure patients), as well as from the apolipoprotein E-deficient mice,
      demonstrates increased susceptibility to oxidation in comparison to normal LDL.
      In some groups of these patients LDL is minimally oxidized already in plasma. 3)
      Supplementation of nutritional antioxidants, which are rich in polyphenols (red
      wine, licorice, olive oil), or of selenium to humans or to the apolipoprotein E
      deficient mice, as well as therapy with beta-hydroxy-beta-methyl-glutaryl-CoA
      reductase inhibitors (so-called "statins") in hyperocholesterolaemic patients,
      were shown to reduce the susceptibility of LDL to oxidation. This effect could be
      associated with a reduction in the size of the atherosclerotic lesion and may
      thus contribute to attenuation of the atherosclerotic process.

PMID- 8877335
TI  - Absence of gastrointestinal absorption or urinary excretion of aluminium from an
      allantoinate complex contained in two antacid formulations in patients with
      normal renal function.
AB  - We studied the plasma and urinary excretion levels of aluminum (Al) on day 0, 10
      and 30 in 79 patients with gastrointestinal symptoms and normal renal function
      who were receiving a complex based on Al allantoinates [C4H5N4 O3 Al (OH)2] and
      [C4H5N4 O3 Cl Al2 (OH)4]. We evaluated the extent of Al absorption after repeated
      administration of this complex in two antacid formulations, Ulfon Lyoc in
      lyophilised tablet form (group 1; n = 40) and Ulfon suspension (group 2; n = 39).
      The total Al load for each antacid and patient was 512 mg daily for a total of
      15360 mg during the 30-day treatment. No significant rise in plasma Al
      concentration was noted with either formulation between day 0 and 10, day 0 and
      30 or day 10 and 30, nor was there any significant increase in urinary excretion
      levels. Al absorption was not increased and no toxic effects were noted,
      indicating that such formulations are suitable for long-term therapy in patients
      with gastrointestinal symptoms.

PMID- 8877336
TI  - Heterogeneity of acute intermittent porphyria: a subtype with normal erythrocyte
      porphobilinogen deaminase activity in Germany.
AB  - Patients with acute intermittent porphyria can be subdivided into three groups,
      according to the porphobilinogen deaminase activity in their erythrocytes. The
      first group has lowered, the second overlapping and the third normal
      porphobilinogen deaminase activity. Of 385 acute intermittent porphyria patients
      5% had normal porphobilinogen deaminase activity. Gene carriers of acute
      intermittent porphyria, which have normal porphobilinogen deaminase activity but
      display slight, moderate or high aberrations of excretion, are recognized by
      analysis of urinary haem precursors and faecal porphyrins. Six individuals
      suffering from acute intermittent porphyria were detected in three families with
      normal porphobilinogen deaminase. There were no differences in the latent and
      clinical phases of acute intermittent porphyria between patients with lowered and
      those with normal porphobilinogen deaminase. One female with normal activity in
      erythrocytes, in which the porphyria disease process is triggered by barbiturates
      and carbamazepine, is presented. After therapy with high doses of glucose and
      omission of inducing agents, this woman was free of symptoms, and the excretion
      of different urinary porphyrin precursors and porphyrins decreased by between 65
      and 93%.

PMID- 8877337
TI  - Arginase activity determination. A marker of large bowel mucosa proliferation.
AB  - Arginase activity of the intestinal mucosa was tested as a proliferative marker
      in the adenoma-carcinoma sequence. The enzyme activity was determined by an end
      point colorimetric method with L-arginine as substrate. Arginase activity was
      evaluated in 430 biopsy samples of large bowel mucosa, polyps and cancer tissue.
      The activities (U/g protein, mean +/- SE; n) were: normal mucosa 83.2 +/- 7.3;
      25, adenomas 199.4 +/- 19.1; 40, carcinomas 1269.7 +/- 174.9; 40, inflammatory
      bowel disease 1210.7 +/- 247.1; 34. The arginase activity differs significantly
      in the adenoma-carcinoma sequence according to the Duncan's test (p < 0.05).

PMID- 8877339
TI  - Determination of plasma protein-bound malondialdehyde by derivative
      spectrophotometry.
AB  - We describe a method for the measurement of protein-bound malondialdehyde with
      the thiobarbituric acid reaction in human plasma using second-derivative
      spectrophotometry. Calibration was done by spectrum height measurement from the
      baseline at 532 nm. The data were compared with those obtained by using
      conventional absorbance and fluorimetric measurements. The results were linear
      from 0.2 to 80 mumol/l and the detection limit was 0.19 mumol/l. Within-run and
      between-run precision, evaluated by analysing pooled normal plasma, were 8 and
      14% respectively. The method was tested for the influence of bilirubin,
      haemoglobin, glucose, urea, uric acid, sucrose and N-acetyl-neuraminic acid which
      interfered in the colorimetric method but not in the technique proposed here. The
      mean (+/-SD) malondialdehyde concentration determined in 59 healthy blood donors
      with the new assay was 0.34 (+/-0.14) mumol/l. This assay procedure could
      represent an alternative to high-performance liquid chromatography for the
      measurement of malondialdehyde in biological media.

PMID- 8877338
TI  - The effects of long term high environmental temperature on cellular enzyme
      activities from different organs.
AB  - The effect of long term hyperthermia on enzyme levels in the chicken heart and
      breast muscles, brain, kidney, liver and lung were studied. Three weeks old
      chickens were exposed to environmental temperature of 24 degrees C (control
      group) and 32 degrees C (experimental) for a duration of 5 weeks, after which the
      birds were sacrificed, organs removed, homogenized and centrifuged at 22,000 g
      for 30 minutes. Enzyme activities in the supernatant were measured. The following
      enzymes were analysed: alanine and aspartate aminotransferase, alkaline
      phosphatase, creatine kinase, lactic dehydrogenase and gamma-glutamyltransferase.
      Significant changes in cellular enzyme activities were seen in the organs
      studied. Based on the percentage of changes compared to the controls, large and
      significant changes were seen in the creatine kinase from heart muscle (mean
      increase of 328%), aspartate aminotransferase from the brain (mean increase of
      148%) and gamma-glutamyltransferase from the kidney (mean increase of 105%). The
      organs showing the smallest changes were breast muscle and liver.

PMID- 8877340
TI  - Detection of short-term fluctuations in measurement systems by determination of
      extreme values and range.
AB  - In the new draft, in preparation, of the guidelines of the German Medical Council
      (Richtlinien der Bundesarztekammer, RiLiBAK) for quality management of clinical
      laboratory measurement systems, particular emphasis is placed on the
      establishment of a lower and upper limit for each control value in a control
      cycle. In the present study, an attempt is made to show that this approach alone
      does not detect even relatively large short-term changes in a measurement system.
      A substantial improvement is possible with modest outlay, by also examining the
      difference between the largest and smallest individual control values, i.e. by
      determining the current range. Appropriate practical limits for this procedure
      are derived from the theoretical behaviour of extreme values, based initially on
      the usual assumption of a normal distribution. Furthermore, it is shown that
      these limits are also meaningful for other assumed appropriate distributions.

PMID- 8877341
TI  - Analytical and clinical implications of soluble transferrin receptors in serum.
AB  - In this study the analytical performances of two recently introduced assays for
      soluble transferrin receptors in serum were tested. The Ramco transferrin assay
      was compared with the Eurogenetics assay. In a small clinical study serum samples
      from patients with anaemia of chronic disease, iron deficiency and
      myelodysplastic syndrome were analysed, as well as sera from healthy volunteers.
      The analytical performances of the Ramco assay were found to be acceptable. In
      the Eurogenetics test however, inter-assay imprecision and the end of run drift
      were unacceptably high. We were able to confirm that in patients with
      uncomplicated iron deficiency the concentration of soluble transferrin receptors
      is higher than in healthy volunteers. In cases of anaemia of chronic and
      inflammatory disease, the levels of soluble transferrin receptors in serum are
      slightly, but not significantly, higher than in normal subjects. Measurement of
      soluble transferrin receptors in serum provides a good differentiation between
      anaemia of chronic disease and iron deficiency.

PMID- 8877343
TI  - Audit in laboratory medicine.
AB  - Laboratory medicine is at a crossroads that provides great opportunities to
      improve the efficacy of the service and its role in healthcare. Many of the new
      roles for laboratory staff will be outside the boundaries of the traditional
      laboratory. These roles include increased emphasis on consultative activities,
      participation in interdisciplinary teams, and efforts to assure appropriate test
      utilization. Audit in laboratory medicine may be defined as a process of review
      and assessment of laboratory performance, and its purpose should be to improve
      patient care by enhancing laboratory performance and making better use of
      resources. Here we discuss the rationale of audit in laboratory medicine, its
      goals as well as its topics. The suggested conduct for an audit and the
      involvement of personnel are also reviewed.

PMID- 8877342
TI  - Interferences of glycerol, propylene glycol, and other diols in the enzymatic
      assay of ethylene glycol.
AB  - As an alternative to gas chromatography, the enzymatic UV assay of ethylene
      glycol is often used by emergency laboratories. Many variants of this technique
      have been published, all based on the reaction between NAD(+) and ethylene glycol
      in the presence of glycerol dehydrogenase (EC 1.1.1.6). We show that other alpha
      diols interfere in this reaction. Some of them, like 2,3-butanediol, give false
      positive reactions; whereas other diols, e.g. glycerol and propylene glycol,
      interfere only when ethylene glycol is present in the sample and lower the
      ethylene glycol response; these interferents are of particular concern because
      some parenteral drugs used in emergency situations contain glycerol or propylene
      glycol in their vehicle. This drawback has hitherto been largely underestimated,
      and we think that ethylene glycol results obtained with these enzymatic
      techniques should be interpreted with caution, even if the sample is pre-treated
      with glycerokinase (EC 2.7.1.30); this pre-treatment effectively corrects the
      glycerol interference but not that of propylene glycol.

PMID- 8877344
TI  - Centrosome dynamics during the meiotic progression in the mouse oocyte.

PMID- 8877345
TI  - Searching for an international name for an old discipline.

PMID- 8877346
TI  - Characterization and classification of external quality assessment schemes (EQA)
      according to objectives such as evaluation of method and participant bias and
      standard deviation. External Quality Assessment (EQA) Working Group A on
      Analytical Goals in Laboratory Medicine.
AB  - Within the scope of this paper, the Working Group has attempted to place external
      quality assessment (EQA) within the whole context of quality management in
      laboratory medicine. First, the objectives of EQA schemes are defined and current
      EQA schemes evaluated. In most schemes, the objectives are not defined a priori
      and do not allow the definition of the origin of unacceptable individual results
      from participants. There is an ongoing trend for making traditional EQA schemes
      more interesting for the participants. Analysis of the factors involved in
      analytical quality allow the definition of the essential analytical tasks of
      educational EQA schemes. Beside these quality control tasks, educational EQA also
      includes quality assurance elements. EQA today has not only an important role to
      play in the assessment of each participant's performance but also in the
      assessment of the method. Efficiency of the schemes and educational impact can be
      improved by appropriate scheme designs according to objectives. After this
      theoretical approach, some practical examples of problem related EQA designs are
      given.

PMID- 8877347
TI  - Methodological and clinical evaluation of two automated enzymatic immunoassays as
      compared with a radioimmunoassay for neuron-specific enolase.
AB  - We evaluated the clinical and methodological features of the neuron-specific
      enolase radioimmunoassay (NSE RIA) (Pharmacia = Ph) with the neuron-specific
      enolase enzyme immunoassay (NSE EIA) on the ES 700 (Boehringer Mannheim = BM) and
      the NSE EIA on the Cobas Core System (Roche = Ro). A total of 253 serum samples
      obtained from 37 healthy persons, 45 patients with benign lung diseases, 124
      patients with lung cancer (42 with small cell lung cancer, 23 with
      adenocarcinoma, 21 with squamous cell carcinoma, 11 with large cell carcinoma,
      and 27 with unknown histology), 34 with lung metastases, 7 patients with sarcoma
      and 6 patients with malign lymphatic diseases were stored at -80 degrees C and
      assayed retrospectively. The intra- and inter-assay imprecisions were lower for
      the automatized test systems than for the RIA. Correlation between the EIA's and
      the RIA was better for NSE (Ro) than for NSE (BM) (BM/Ph: r = 0.93 and slope =
      0.54; Ro/Ph: r = 0.95, slope = 0.79), but weaker than the correlation between the
      two EIA's: over the whole range r = 0.96, neuron-specific enolase < 50
      micrograms/l: r = 0.97, neuron-specific enolase < 20 micrograms/l: r = 0.92.
      Fixing the specificity at 95% versus benign lung diseases we found a cut off
      value of 11.9 micrograms/l for NSE RIA (Ph), 15.9 micrograms/l for NSE EIA (BM)
      and 13.5 micrograms/l for NSE EIA (Ro). Based on this specificity of 95% versus
      benign lung diseases as the clinically relevant reference group, the sensitivity
      for NSE RIA was 32% for all lung cancer and 45% for small cell lung cancer, for
      NSE EIA (BM) 35% for all lung cancer and 43% for small cell lung cancer, the NSE
      EIA (Ro) had a sensitivity of 42% for all lung cancer and 57% for small cell lung
      cancer. In a follow-up study of two patients with small cell lung cancer a good
      comparability for all three assays in the kinetics, but a marked difference in
      the neuron-specific enolase value levels was found. The results show that the NSE
      EIA (Ro) on Cobas Core system is the most sensitive assay for the detection of
      small cell lung cancer.

PMID- 8877348
TI  - The use of omeprazole for resistant oesophagitis in children.
AB  - Following failure of conventional therapy for reflux oesophagitis, 15 children
      were treated with omeprazole 20 mg daily for a period of up to three months
      initially. Treatment resulted in a marked symptomatic improvement as measured by
      incidence of pain, vomiting, dysphagia and haematemesis. Four children failed
      treatment and required fundoplication. No complications from the use of
      omeprazole were recorded and some children have continued long-term treatment.

PMID- 8877349
TI  - Effects of prednisolone and dexamethasone in children with alkali burns of the
      oesophagus.
AB  - We compared the efficacies of prednisolone and dexamethasone for treatment of
      children with oesophageal burns due to ingestion of caustic substances. The
      criteria of efficacy used were a) stricture severity by 3 weeks post-ingestion,
      b) reduction in burn severity by 3 weeks post-ingestion and c) number of
      dilatations required over the first year post-ingestion. Thirty-six children (24
      boys and 12 girls; mean age 23.6 +/- 7.4 months) were selected from a total of 63
      patients admitted over a ten-year period to the General Hospital of Galicia with
      second- or third-degree oesophageal burns due to accidental ingestion of liquid
      alkali preparations. The patients were divided into two groups of 18, one group
      for treatment with prednisolone (2 mg/kg/day) and the other for treatment with
      dexamethasone (1 mg/kg/day). Strictures developed in 12 (66.7%) of the children
      in the prednisolone-treated group and only 7 (38.9%) of the children in the
      dexamethasone-treated group. Severe strictures developed in 10 (55.6%) of the
      children in the prednisolone-treated group and only 5 (27.8%) of the children in
      the dexamethasone treated group. However, there was no significant difference
      between the groups in the posttreatment distribution of stricture-severity
      ratings. Burn healing was significantly better in the dexamethasone-treated
      group. Similarly, the number of dilatations necessary during the first year of
      treatment was significantly lower in the dexamethasone-treated group. Our results
      thus indicate that, by comparison with prednisolone, dexamethasone leads to
      improved burn healing and reduced need for dialatations during the first year
      post-injury.

PMID- 8877350
TI  - Motor function of the esophagus after caustic burn.
AB  - During the subacute and chronic phases of esophagitis due to ingestion of a
      caustic substance, the patient commonly displays stricture, esophageal rigidity
      and dysphagia. We used esophageal manometry, radiology, pH monitoring and 99mTc
      scintigraphy to investigate esophageal motor function in 25 children (mean age 24
      +/- 7 months) with chronic esophagitis after second- and/or third-degree caustic
      burns. The results were compared with those for a control group of 12 children
      (mean age 32 +/- 19 months) under surveillance for suspected gastroesophageal
      reflux (GER) but for whom this pathology was later ruled out. Seventeen (68%) of
      the lesioned-group children showed esophageal dysfunction as revealed by
      monitoring of pH over a 24-hour period. Over this period, the mean percentage of
      time with pH below 4 was 19 +/- 10%, the mean number of reflux episodes was 48 +/
      52, the mean number of reflux episodes lasting longer than 5 min was 10 +/- 5,
      and the mean duration of the longest reflux episode was 51 +/- 21 min. Manometry
      indicated that, in the lesioned group, an average of 77 +/- 18% of peristaltic
      waves were nonpropulsive, while the mean Esophageal Work Index (number of
      propulsive waves per hour x mean maximum pressure developed during propulsive
      waves) was 227 +/- 192 units. All of the above means were significantly different
      (p < 0.01) from the corresponding control-group means. Esophageal strictures were
      observed in 60% (15) of the children. In 2 cases it was minimal, 2 cases moderate
      and 11 cases had severe strictures. 99mTc scintigraphy indicated that esophageal
      transit was slightly delayed in four, moderately delayed in five and severely
      delayed in 16 of the lesioned-group subjects. There was close correspondence
      between the results of manometry and scintigraphy as regards severity of
      esophageal dysfunction. These results indicate that motility disturbances and GER
      are very frequent sequelae of caustic burns of the esophagus, and should be taken
      into account when evaluating symptoms and deciding on the therapeutic strategy
      (including diet) to be followed.

PMID- 8877351
TI  - Bladder exstrophy in Sweden--a long-term follow-up study.
AB  - A retrospective review of all new cases of bladder exstrophy in Sweden in 1970
      through 1989 is presented. The aim was to evaluate management of the malformation
      in Sweden and possibly identify factors that might improve the outlook. The
      incidence was 1:33,500 births. Records were reviewed of the 61 children (37 males
      and 24 females) treated at Sweden's four specialist centers of pediatric surgery.
      There was one perinatal death. Primary management was mainly early bladder
      closure (within 72 hours), late closure or perinatal urinary diversion.
      Subsequent measures included augmentation cystoplasty, bladder neck
      reconstruction, provision of continent urinary reservoir and penile
      reconstruction. The follow-up time was 4-19 years. In 15 cases renal scarring
      developed, though with impairment of total function in only three. Ten patients
      achieved continence, defined as 3-hour dry intervals, of whom four had urinary
      reservoirs with continent stoma. Urinary tract infections were recorded during
      follow-up in 43% of the surviving patients, though the true incidence of
      infection presumably was higher. To improve management of bladder exstrophy in
      sparsely populated Sweden, a nation-wide strategy of ongoing interhospital
      collaboration has been adopted. Results will be continuously presented.

PMID- 8877352
TI  - One-stage reconstruction of bladder exstrophy.
AB  - From 1984 to 1990 a primary one-stage reconstruction of bladder exstrophy was
      performed at our hospital on 15 consecutive infants. Reconstruction included
      Cohen's ureteral reimplantation, bladder neck reconstruction according to Young
      Dees, bladder closure, symphyseal bone approximation, abdominal wall closure, and
      repair of epispadias in females. Postoperatively, all patients were immobilized
      by overhead extension. Iliac osteotomy was done in 9 children, but was abandoned
      in recent years for infants less than one month old Follow-up examinations
      included an interview with the parents, clinical examinations, blood and urine
      analyses, uroflowmetry, and ultrasound scan of the abdomen. Nuclear renal scan,
      i.v. pyelography, and cystography were carried out as indicated. At the time of
      last evaluation the children were between 3 and 9 years of age. The cosmetic
      results were satisfactory in all cases. Eight of 15 children were dry day and
      night with micturition intervals more than 3 hours during day time (complete
      continence). Five children were dry during day time with micturition intervals up
      to 3 hours, but occasionally wet their beds (partial continence). Two children
      were incontinent. Eleven of 15 children had a bladder capacity of more than 100
      ml. Renal function was normal in all patients. Two children showed a mild VUR,
      and no other abnormalities of the upper urinary tracts were found. Iliac
      osteotomy did not influence the functional or cosmetic results, but in two
      patients asymmetry of pelvic bones with consecutive lumbar scoliosis was found.
      Comparing these results with reports on staged reconstructive procedures, we
      conclude that by primary complete one-stage reconstruction a well acceptable
      success rate is achieved, and that by this method possibly some advantages are
      offered to patients with bladder exstrophy.

PMID- 8877353
TI  - Extravesical detrusor tunneling: a variant of antireflux procedure.
AB  - Detrusor tunneling procedure is an extravesical technique, which provides
      antireflux implantation of different tube systems (ureter, appendix, tubularized
      preputial flap, tapered ileum). The main characteristic of the technique is the
      formation of extravesical submucosal tunnel by creating a bridge from the
      unresected bladder muscle under which the tube is passed. During the period from
      January 1987 to July 1995, the technique was performed on 442 different tube
      systems: 402 ureters, 12 appendices, 26 tubularized preputial flaps and 2 tapered
      ileums. Patients were aged from 15 days to 42 years (mean 39 months). Follow-up
      was from 2 months to 8 years (mean 2.9 years). Postoperative complications
      occurred in 11 cases. There were 3 stenoses and 5 refluxes in
      ureteroneocystostomies, and one stenosis and 2 urine leakages in continent
      cutaneous vesicostomies. The extravesical detrusor tunneling procedure could be a
      very useful method for antireflux implantation of various tube systems.

PMID- 8877354
TI  - Long-term bladder dysfunction in boys with posterior urethral valves.
AB  - We report a series of 60 children operated on for posterior urethral valve (PUV)
      before the age of 5 years and followed up for 10 years. This work aims to study
      the vesico-sphincteric sequelae of this malformation. 38 patients showed early
      urinary incontinence post-operatively. Of them, 20 were re-evaluated 10 years
      later by pelvic ultrasonography, pressure flow studies combined with EMG and
      assessment of renal function. 8 patients refused to undergo these investigations
      and 10 were lost to follow-up. Of the 28 evaluable patients, 22 are currently
      continent and a complete urodynamic study was performed for the 6 (10%)
      incontinent patients. Of them, 3 showed uninhibited detrusor contractions. The
      vesical compliance was frequently within the normal limits. No case of detrusor
      sphincteric dyssynergy or urethral hypotony was found. 2 were successfully
      treated by oxybutinin and biofeedback reeducation, 2 were partially improved but
      their prostates are still in growth and the possibility of implanting an
      artificial sphincter was discussed in the remaining 2. The urodynamic evaluation
      of those patients in the long-term is encouraging.

PMID- 8877355
TI  - Escalator injuries in Genevan children: a report of 6 cases.
AB  - We present a retrospective survey of the mechanism and the lesions caused by
      escalators in Genevan children. Though these accidents are rare, they are often
      very serious. They occur primarily among children around the age of three and
      affect especially the hand. It is not economically feasible to replace or modify
      current escalators. It is therefore important that the current warning signs on
      escalators be improved. As there is a specific risk to children of catching
      fingers in the escalator and most parents are unaware of this type of danger, a
      warning sign with an explicit illustration could be of value. Also an insertion
      of a plastic bar just above the moving stairs on each lateral wall would block
      any potential extremities from being caught in the gap between the steps and the
      side of the staircase.

PMID- 8877356
TI  - Ectopic cervical thymus: case report.
AB  - Ectopic cervical thymus is rarely considered in the differential diagnosis of
      cervical masses: this lesion is essentially asymptomatic and generally occupies a
      position in the neck along the carotid sheath, underneath the sterno-cleido
      mastoid muscle. It is supposed that most of these masses arise as a consequence
      of migration defects during glandular embryogenesis. Ectopic thymus rarely
      invades contiguous structures but in the literature some cases of malignant
      transformation of aberrant cervical thymus have been reported. Some non-invasive
      investigations (MRI, ultrasonography) are useful but accurate diagnosis depends
      eventually on surgical excision and histologic examination.

PMID- 8877357
TI  - Management of thoracolaryngopelvic dysplasia.
AB  - We report a family in which three members have thoracolaryngopelvic dysplasia
      (Barnes' syndrome). This family illustrates the phenotypic variability seen in
      this rare clinical entity and highlights the medical and surgical management
      necessary in such cases.

PMID- 8877358
TI  - Early infantile hypertrophic pyloric stenosis: surgery at 26 hours of age.
AB  - A newborn baby with hypertrophic pyloric stenosis on the first day of life is
      presented with a review of the literature regarding this early age of onset. The
      average age at onset of symptoms is usually 3.5 weeks. Very rarely symptoms start
      at birth or are sometimes delayed until 3 months of age or more (20). There are
      several reports (2, 3, 5, 6, 11, 14, 18, 19) of infants with onset of symptoms
      and eventual operation within the first day or two of life and indeed with
      vomiting from birth (2, 3, 5, 6, 11, 14, 18, 19). To our knowledge this case
      report documents the youngest baby ever operated upon for infantile hypertrophic
      pyloric stenosis at 26 hours of age.

PMID- 8877359
TI  - Splenic leiomyoma: an uncommon localization.
AB  - Muscle cell tumors are very uncommon in the spleen as they are in ataxia
      telangiectasia. The increased frequency of chromosome breaks probably because of
      a defect in DNA repair favors the development of benign or malignant tumors in
      the patient. A case of leiomyoma of the spleen in an 8-year-old boy with ataxia
      telangiectasia is reported. The literature on the splenic masses and the
      localization of leiomyoma is reviewed.

PMID- 8877360
TI  - Solid and cystic tumor of the pancreas--case report.
AB  - Pancreatic tumors are rarely present in childhood. The authors present a case of
      papillary-cystic tumor in a 13-year-old girl, treated by partial
      pancreatoduodenectomy, with preservation of the pylorus. The histologic pattern
      was of a papillary cystic tumor without evident atypical nuclei. One year after
      operation, the girl is well without any finding of disease.

PMID- 8877361
TI  - Post-traumatic vulvar endometriosis.
AB  - We report a case of vulvar endometriosis presenting as a vulvar mass following
      trauma in a 12 years old, 3 months post-menarcheal girl. The presumptive etiology
      is the direct implantation of endometrial cells. Painful swelling of the vulvar
      mass appeared gradually during menses. Excision of suspected vulvar endometriosis
      is suggested as the definite treatment.

PMID- 8877362
TI  - Total tubular duplication of the colon and distal ileum combined with
      transmesenteric hernia: surgical management and long-term-results.
AB  - A two-year-old male with total tubular duplication of the colon and distal ileum
      combined with transmesenteric hernia is presented. Recurrent abdominal pain,
      distention of the abdomen and chronic constipation were the main complaints. A
      side-to-side anastomosis created through the lowermost part of the common wall of
      the duplication and colon proper, plus closure of the mesenteric defect and
      excision of the duplicated ileal loops relieved the patient of all symptoms.
      Postoperative stagnation of the stool in the closed hollow end of the duplication
      caused distention developing into a prolapsing pouch which required excision by
      transanal approach six years after the laparotomy.

PMID- 8877363
TI  - Waardenburg-Hirschsprung disease in two sisters: a possible clue to the genetics
      of this association?
AB  - A Tunisian infant of consanguineous parents had pigmentary disorders, congenital
      deafness and long-segment Hirschsprung disease. Her elder sister had the same
      disorders but with short-segment aganglionosis. Their father, mother and two
      brothers are healthy without history of deafness, constipation or pigmentary
      disorder. We confirm that this Waardenburg-Hirschsprung association seems to be a
      distinct clinical entity with a possible autosomal recessive mode of inheritance.
      Linkage analyses performed in this family support the view that neither the RET
      locus (candidate for familial dominant Hirschsprung disease) nor the HuP2 locus
      (candidate for Waardenburg syndrome type I) are involved in the disease
      phenotype. We suggest that Waardenburg-Hirschsprung complex is a distinct genetic
      entity and at least one additional locus altering cranial neural crest cell
      development is responsible for pleiotropic features observed in this association.

PMID- 8877364
TI  - Proteus syndrome associated with a sacrococcygeal teratoma; a rare combination.
AB  - We report on an 5-year-old boy with a Proteus syndrome known since his second
      year of life. Hidden in a lipomatous tumor we excised a sacrococcygeal teratoma
      which must have been present since birth. This is the first case, out of about 50
      published Proteus cases, of a patient with Proteus syndrome and sacrococcygeal
      teratoma.

PMID- 8877365
TI  - Regarding the specificity of Newcastle disease virus sialidase.

PMID- 8877366
TI  - Workshop to establish databases of carbohydrate spectra.

PMID- 8877367
TI  - Preparation of radiolabeled gangliosides.

PMID- 8877368
TI  - Brain extracellular matrix.
AB  - The extracellular matrix of the adult brain tissue has a unique composition. The
      striking feature of this matrix is the prominence of lecticans, proteoglycans
      that contain a lectin domain and a hyaluronic acid-binding domain. Hyaluronic
      acid and tenascin family adhesive/anti-adhesive proteins are also abundant.
      Matrix proteins common in other tissues are nearly absent in adult brain. The
      brain extracellular matrix appears to have trophic effects on neuronal cells and
      affect neurite outgrowth. The unique composition of this matrix may be
      responsible for the resistance of brain tissue toward invasion by tumors of non
      neuronal origin.

PMID- 8877369
TI  - Isolation of the ALG6 locus of Saccharomyces cerevisiae required for
      glucosylation in the N-linked glycosylation pathway.
AB  - N-Linked protein glycosylation in most eukaryotic cells initiates with the
      transfer of the oligosaccharide Glc3Man9GlcNAc2 from the lipid carrier dolichyl
      pyrophosphate to selected asparagine residues. In the yeast Saccharomyces
      cerevisiae, alg mutations which affect the assembly of the lipid-linked
      oligosaccharide at the membrane of the endoplasmic reticulum result in the
      accumulation of lipid-linked oligosaccharide intermediates and a
      hypoglycosylation of proteins. Exploiting the synthetic growth defect of alg
      mutations in combination with mutations affecting oligosaccharyl transferase
      activity (Stagljar et al., 1994), we have isolated the ALG6 locus. alg6 mutants
      accumulate lipid-linked Man9GlcNAc2, suggesting that this locus encodes an
      endoplasmic glucosyltransferase. Alg6p has sequence similarity to Alg8p, a
      protein required for glucosylation of Glc1Man9GlcNAc2.

PMID- 8877370
TI  - Specificity of xenoreactive anti-Gal alpha 1-3Gal IgM for alpha-galactosyl
      ligands.
AB  - The transplantation of organs from lower animals such as pigs into humans is
      prevented by a severe rejection reaction initiated by complement fixing
      xenoreactive natural antibodies. Most anti-pig xenoreactive natural antibodies in
      humans are thought to recognize Gal alpha 1-3Gal beta 1-4GlcNAc and are also
      thought to recognize, albeit less avidly, Gal alpha 1-6Glc. Gal alpha 1-6Glc has
      been used as a ligand for purification of 'anti-Gal alpha 1-3Gal antibodies' and
      as a therapeutic or reagent to prevent the binding of these antibodies to porcine
      organs or cells. We tested the specificity of anti-Gal alpha 1-3Gal IgM for Gal
      alpha 1-6Glc and related saccharides. Based on inhibition of binding of
      xenoreactive anti-Gal alpha 1-3Gal IgM to porcine cells by soluble saccharides,
      anti-Gal alpha 1-3Gal IgM in a human serum was found to consist of a mixture of
      antibodies which have a similar affinity for Gal alpha 1-3Gal but varying
      affinities for Gal alpha 1-6Glc and other structures. Twenty to 40% of the anti
      Gal alpha 1-3Gal IgM from the population tested did not recognize Gal alpha 1
      6Glc. The binding of anti-Gal alpha 1-3Gal IgM to Gal alpha 1-6Glc varied widely
      from individual to individual, some samples lacking almost entirely anti-Gal
      alpha 1-3Gal IgM which bound to Gal alpha 1-6Glc.

PMID- 8877371
TI  - Structure of the N-linked oligosaccharide of the main diagnostic antigen of the
      pathogenic fungus Paracoccidioides brasiliensis.
AB  - The major diagnostic antigen of Paracoccidioides brasiliensis is the
      exocellularly secreted 43,000 Da glycoprotein (gp43) which contains a single N
      linked oligosaccharide chain. This oligosaccharide, although poorly immunogenic
      in man, is responsible for the cross-reactivity of the gp43 with sera from
      patients with histoplasmosis, and may have a role in fungal virulence. It
      contains a neutral high-mannose core (Man7GlcNAc2) to which a (1-->6)-linked
      alpha-D-Manp chain of variable length, substituted at the 2-O positions by single
      alpha-D-Manp residues, is attached. A terminal unit of beta-D-galactofuranose is
      (1-->6)-linked to one of the (1-->2)-linked mannosyl residues, either in the C or
      in the A arm of the oligosaccharide. The heterogeneity of the oligosaccharide is
      determined by the different sizes of the A arm and the sites of insertion of the
      beta-galactofuranosyl unit. The complete structure was determined by methylation
      analysis, 1H-NMR, mass spectrometry, acetolysis and mannosidase degradation.
      Electrospray mass spectrometry showed that the oligosaccharide comprises several
      subtypes ranging from Hex18GlcNAc2 to Hex10GlcNAc2 which accounts for the diffuse
      migration of the gp43 in polyacrylamide gels. The average size of the most
      frequent subtype is Hex13.6GlcNAc2. Dilute acid treatment to remove beta-D-Galf
      reduced the molecular masses of the majority of the subtypes by a single sugar
      unit.

PMID- 8877372
TI  - Hapten inhibitors of the endogenous galactose binding lectins and anti-lectin
      antibodies inhibit primitive streak formation in the early chick embryo.
AB  - The early chick blastoderm expresses two endogenous galactose-binding lectins of
      14 kDa and 16 kDa. We have studied the effect the lectin hapten inhibitors
      thiodigalactoside and the synthetic neoglycoprotein lactosyl-bovine serum albumin
      as well as polyclonal anti-lectin antibodies on the development of early chick
      embryos cultured in a defined medium. Controls consisted of maltose, maltosyl
      bovine serum albumin and rabbit IgG. Embryos treated at the onset of cell
      migration during early gastrulation underwent blastoderm retraction with decrease
      in surface area. In addition, they exhibited a lack of demarcation between the
      presumptive embryonic area (area pellucida) and the presumptive extraembryonic
      area (area opaca). These blastoderms also lacked a primitive streak, that is, the
      structure that forms in the area pellucida during gastrulation as cell migrate to
      form the endodermal and mesodermal layers of the embryo. Embryos treated at later
      stages of gastrulation showed development similar to that of controls in that
      they were able to undergo early organogenesis. The results suggest that lectin
      mediated mechanisms are essential for the migratory movements of early
      gastrulation and that, at late gastrulation, other mechanisms exist in the embryo
      to compensate for lectin function.

PMID- 8877374
TI  - Crystal and molecular structure of a histo-blood group antigen involved in cell
      adhesion: the Lewis x trisaccharide.
AB  - This work describes the first crystal structure ever reported of a histo-blood
      group carbohydrate antigen: Le(x). This study provides a detailed description of
      the conformation of two crystallographic independent molecules in a highly
      hydrated environment along with their hydrogen bonding properties and packing
      features. Some interactions observed between adjacent trisaccharides can provide
      the basis for involvement of Le(x)-Le(x) interactions in cell-cell adhesion.

PMID- 8877373
TI  - Purification, biochemistry and molecular cloning of an insect
      glycosylasparaginase from Spodoptera frugiperda.
AB  - Glycosylasparaginase (EC 3.5.1.26) from Sf9 cells (Spodoptera frugiperda) was
      purified to homogeneity with a specific activity of 2.1 unit/mg. The enzyme is
      composed of two non-identical alpha/beta subunits joined by strong non-covalent
      forces and has one glycosylation site located in the alpha subunit. Molecular
      masses of the subunits were determined to be 28 kDa and 17 kDa by SDS-PAGE.
      Native enzyme existed in quaternary structures of either heterodimer (alpha beta)
      or heterotetramer (alpha 2 beta 2). These forms exhibited different ionic
      characteristics during DE52 anion exchange chromatography, and their molecular
      masses were determined to be 47 kDa and 101 kDa by gel filtration. The enzyme was
      thermostable, requiring 65-70 degrees C to be denatured, and it had a broad pH
      optimum from 4-10.5 with a pKa around 6. SDS easily inactivated the enzyme. The
      K(m) of glycosylasparaginase for its normal substrate GlcNAc-Asn was 0.88 mM. The
      enzyme also exhibited asparaginase activity with a K(m) of 3.0 mM for asparagine.
      N-terminal amino acids of the denatured subunits were sequenced and degenerate
      primers were designed for cloning its cDNA using PCR and 5' and 3' RACE.
      Glycosylasparaginase cDNAs from bovine and rat were also cloned using similar
      strategies, and primary structures of glycosylasparaginases from six species
      (human, bovine, rat, mouse, Sf9 cells and Flavobacterium) have been compared and
      related to a recent crystal structure of the human enzyme.

PMID- 8877375
TI  - Characterization of two mannose-binding protein cDNAs from rhesus monkey (Macaca
      mulatta): structure and evolutionary implications.
AB  - Mannose-binding proteins (MBPs), members of the collectin family, have been
      implicated as lectin opsonins for various viruses and bacteria. Two distinct but
      related MBPs, MBP-A and MBP-C, with approximately 55% identity at the amino acid
      level, have been previously characterized from rodents. In humans, however, only
      one form of MBP has been characterized. In this paper we report studies
      elucidating the evolution of primate MBPs. ELISA and Western blot analyses
      indicated that rhesus and cynomolgus monkeys have two forms of MBP in their sera,
      while chimpanzees have only one form, similar to humans. Two distinct MBP cDNA
      clones were isolated and characterized from a rhesus monkey liver cDNA library.
      Rhesus MBP-A is closely related to the mouse and rat MBP-A, showing 77% and 75%
      identity at the amino acid level, respectively. Rhesus MBP-A also has three
      cysteines at the N-terminus, similar to mouse and rat MBP-A and human MBP. Rhesus
      MBP-C shares 90% identity with the human MBP at the amino acid level and has
      three cysteines at the N-terminus, in contrast to two cysteine residues found in
      rodent MBP-C. A stretch of nine amino acids close to the N-terminus, absent in
      both mouse and rat MBP-A, but present in rodent MBP-C, chicken and human MBPs, is
      also found in the rhesus MBP-A. The phylogenetic analysis of rhesus and other
      mammalian MBPs, coupled with the serological data suggest that at least two
      distinct MBP genes existed prior to mammalian radiation and the hominoid ancestor
      apparently lost one of these genes or failed to express it.

PMID- 8877376
TI  - Differential ligand binding by two subunits of the rat liver asialoglycoprotein
      receptor.
AB  - The rat liver asialoglycoprotein receptor consists of two types of subunits, a
      predominant polypeptide designated rat hepatic lectin 1 (RHL-1) and a minor
      polypeptide, RHL-2/3, that comes in two differentially glycosylated forms. The
      exact stoichiometry and arrangement of the subunits in the RHL oligomer are not
      known. The carbohydrate-recognition domain of RHL-2/3 has been prepared by
      limited proteolysis of the liver receptor so that its properties can be compared
      with those of the corresponding domain of RHL-1 previously produced in a
      bacterial expression system. Binding studies indicate that while RHL-1 binds N
      acetylgalactosamine with approximately 60-fold higher affinity than it binds
      galactose, RHL-2/3 has only 2-fold selectivity for N-acetylgalactosamine. In
      general, the pattern of monosaccharide-binding specificity for RHL-2/3 is similar
      to RHL-1, but the discrimination of various sugars relative to galactose is
      reduced substantially. Limited proteolysis and crosslinking studies demonstrate
      that RHL-2/3 is easily removed from the RHL oligomer in detergent solution and
      that RHL-1 remains at least trimeric following removal of RHL-2/3. These studies
      suggest that RHL-1 forms a ligand-binding core while RHL-2/3 acts more as an
      accessory subunit contributing to selective binding of certain oligosaccharide
      structures.

PMID- 8877377
TI  - RNA molecules lighting up under the microscope.
AB  - RNA in situ hybridization is a useful method for localizing specific mRNAs and
      studying the spatial and temporal organization of RNA transcription, processing
      and transport in cells. In this review, I describe methods of RNA in situ
      hybridization for tissue sections and cell preparations. Special emphasis is
      placed on the application of non-radioactive-labeled probes for multiparameter
      cell analysis. In addition, a summary of RNA in situ hybridization studies on RNA
      transport in the cytoplasm as well as in the nucleus of cells is given.

PMID- 8877379
TI  - Standardized AgNOR analysis: its usefulness in surgical oncology.
AB  - Recent improvements both in the staining quality and computer-aided quantitation
      of silver-stained nucleolar organizer region (AgNOR)-associated proteins offer
      the possibility to reliably investigate these proteins on routinely processed
      archival material. This article deals with the historical background, the recent
      introduction of a standardized quantitation, the clinical relevance, and future
      perspective for AgNOR evaluation. It is specifically emphasized that AgNOR
      analysis after both standardized staining and computer-aided quantitation (as
      recommended by the Committee on AgNOR Quantitation of the European Society of
      Pathology) is now regarded as the gold standard whenever routinely formalin-fixed
      and paraffin-embedded material is investigated.

PMID- 8877378
TI  - Multiparameter microscopic analysis of nucleolar structure and ribosomal gene
      transcription.
AB  - A survey of novel microscopic approaches for structural and functional analysis
      of subnucleolar compartments will be presented. Research on nucleolar structure
      and function concentrates predominantly on two distinct types of nucleoli: (1)
      nucleoli present during the interphase of the cell cycle in somatic tissue
      culture cells and (2) nucleoli present in meiotic cells, e.g. oocytes of
      amphibians. These nucleoli are found during meiotic prophase of oogenesis and are
      functional during several months of the diplotene stage of oogenesis. A further
      characteristic is the fact that these nucleoli are extrachromosomal, since they
      originate by selective ribosomal DNA (rDNA) amplification during the early
      pachytene stage of oogenesis. Miller-type chromatin spread preparations using
      transcriptionally active nucleoli, to a major part, contributed to our
      understanding of the structural organization of polymerase I directed pre-rRNA
      transcription. Although the structural organization of the template-associated
      pre-rRNA transcript is known in some detail from chromatin spreads, relatively
      little is known about structural aspects of pre-rRNA processing. In order to
      investigate this intriguing question in more detail, we have developed a computer
      based densitometry analysis of both template-associated and template-dissociated
      pre-rRNA transcripts in order to follow the structural modification of pre-rRNA
      transcripts during processing. Another line of experiments is devoted to the in
      situ structure of actively transcribing genes in the nucleolus. In order to
      bridge the gap between light microscopy and electron microscopy we started video
      enhanced light microscopical analysis of actively transcribing genes. Although
      the dimensions of individual spread genes are critical for detection by optical
      microscopy, we succeeded in obtaining the first series of images of transcribing
      genes in their "native' hydrated state. An additional promising type of
      microscopy is transmission X-ray microscopy. Recent progress in instrumentation
      as well as in sample preparation has allowed us to obtain the first images of
      density distribution within intact, fully hydrated nucleoli using amplitude
      contrast and/or phase-contrast X-ray microscopy of non-contrasted, fully hydrated
      nucleoli at different states of transcriptional activity. Whereas the above
      mentioned investigations using video microscopy and X-ray microscopy are
      predominantly applicable to the analysis of amplified nucleoli in amphibian
      oocytes, which are characterized by an extremely high transcription rate of 80
      90% of rDNA genes per individual nucleolus, structural analysis of the in situ
      arrangement of actively transcribing genes in somatic nucleoli as present in the
      interphase nucleus is far more difficult to perform, mainly due to the much lower
      number of simultaneously transcribed active genes per individual nucleolus.
      Visualization of actively transcribed gene clusters is approached by an
      integrated experimental assay using video microscopy, confocal laser scan
      microscopy, and antibodies against specific nucleolar proteins.

PMID- 8877380
TI  - Thomsen-Friedenreich-related carbohydrate antigens in normal adult human tissues:
      a systematic and comparative study.
AB  - A broad variety of normal human tissues were examined for the expression of
      Thomsen-Friedenreich (TF)-related histo-blood group antigens, TF (Gal beta 1
      3GalNAc alpha 1-R), Tn (TF precursor, GalNAc alpha 1-R), sialosyl-Tn (NeuAc alpha
      2-6GalNAc alpha 1-R), considered to be useful in cancer diagnosis and
      immunotherapy, and sialosyl-TF, the cryptic form of TF. These antigens or, more
      correctly, glycotopes, were determined by immunohistochemistry with at least two
      monoclonal antibodies (mAbs) each (except sialosyl-TF) as well as by lectin
      histochemistry. For a better dissection of sialosyl-TF and TF glycotopes, tissue
      sections were pretreated with galactose oxidase or the galactose oxidase-Schiff
      sequence. Staining with mAbs appeared to be more restricted than with the lectins
      used. Distribution patterns among normal epithelia were different for all four
      antigens. These antigens were also detected in some non-epithelial tissues. They
      can be classified in the following sequence according to the frequency of their
      occurrence in normal tissues: sialosyl-TF > > sialosyl-Tn > Tn > TF. Most of the
      positively staining sites for TF, Tn, and sialosyl-Tn are located in
      immunologically privileged areas. The complex results obtained with anti-TF mAbs
      (after treatment of the tissue sections with sialidase from Vibrio cholerae) and
      the lectins amaranthin and jacalin revealed a differential distribution of the
      subtypes of sialosyl-TF [NeuAc alpha 2-3Gal beta 1-3GalNAc alpha 1-R and Gal beta
      1-3 (NeuAc alpha 2-6)GalNAc alpha 1-R] in normal human tissues. From our data it
      can be inferred that TF, Tn, and sialosyl-Tn are promising targets for a cancer
      vaccine.

PMID- 8877381
TI  - Connexin 43 and the glucose transporter, GLUT1, in the ciliary body of the rat.
AB  - To investigate the relationship between the gap junction protein connexin 43 and
      the glucose transporter GLUT1, their localization was visualized by double
      immunofluorescence microscopy using frozen sections as well as immunogold
      staining of ultrathin frozen sections. In pigmented epithelial cells, most of the
      GLUT1 was localized along the plasma membrane facing the blood vessels, whereas
      in non-pigmented epithelial cells, it was present along the plasma membrane
      facing the aqueous humor. Connexin 43 was abundant in the ciliary body and
      localized mainly in the gap junctions connecting the pigmented and non-pigmented
      epithelial cells. Localization of GLUT1 and connexin 43 in the blood-aqueous
      barrier suggests that GLUT1, connexin 43, and GLUT1 disposed in this order could
      be a machinery responsible for the transport of glucose across the blood-aqueous
      barrier.

PMID- 8877382
TI  - Ion microscopic imaging of calcium during 1,25-dihydroxyvitamin D-mediated
      intestinal absorption.
AB  - A combination of ion microscopic and conventional radionuclide techniques was
      employed to investigate the temporal-spatial dynamics of 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3]-stimulated intestinal calcium (Ca) absorption. At varying times
      following the administration of a single intravenous dose of 1,25(OH)2D3 to
      vitamin D-deficient chicks, transepithelial transport and tissue retention of Ca
      were quantitated in vivo, using the ligated duodenal loop technique and 47Ca as
      the tracer. The localization of Ca in the intestinal tissue during absorption was
      monitored by ion microscopy, using the stable Ca isotope, 44Ca, as the absorbed
      species. There was little transepithelial absorption of Ca in the vitamin D
      deficient animals despite a substantial tissue accumulation of luminally derived
      Ca, the latter localizing predominantly in the brush border region of the
      enterocyte, as shown by the 44Ca-ion microscopic images. The early (30 min-1 h)
      response to 1,25(OH)2D3 was an increased tissue uptake of luminal 47Ca, which
      also primarily associated with the brush border region, again as shown by ion
      microscopy. At 2-4 h after the 1,25(OH)2D3 dose, there was a progressive
      redistribution of Ca from the brush border region throughout the cytoplasm and
      into the lamina propria. At 8-16 h, 47Ca absorption was maximal and 44Ca was
      sparsely distributed in the intestinal tissue. 47Ca absorption gradually declined
      and reached pre-dose levels by 72 h. At this time, tissue 44Ca was again largely
      limited to the brush border region. These results provide support for the
      multiple actions of 1,25(OH)2D3 on the intestinal Ca absorption process. The ion
      microscopic images provided unique information on the specific time-dependent
      changes in the tissue localization of Ca during the process of its intestinal
      absorption as affected by 1,25(OH)2D3.

PMID- 8877383
TI  - Histochemical staining of cadmium with 2-(8-quinolylazo)-4,5-diphenylimidazole.
AB  - In order to develop a stain with increased sensitivity and selectivity for
      cadmium (Cd), we synthesized and characterized 2-(8-quinolylazo)-4,5
      diphenylimidazole (QAI). This chelating agent was more than twice as sensitive
      for Cd than the best conventional staining agents, including benzothiazolylazo
      beta-naphthol. Differentiation between Cd and zinc (Zn) was achieved by immersing
      tissue sections in TRIS(2-aminoethyl)amine before they were stained with QAI.
      This pretreatment made it possible to selectively stain for Cd by blocking Zn.

PMID- 8877384
TI  - Fluorescence in situ hybridization with cosmid clones for the detection of human
      cytomegalovirus DNA in peripheral blood leukocytes.
AB  - Radioactive in situ hybridization techniques or enzymatic detection procedures of
      hapten-modified human cytomegalovirus (HCMV) probes have been widely used for
      studying the infection of peripheral blood leukocytes with HCMV. This report
      describes significant improvements in terms of signal resolution which can be
      obtained by applying a highly sensitive fluorescence in situ hybridization (FISH)
      technique in conjunction with a large subgenomic HCMV DNA probe. Three cosmid
      clones spanning 119.1 kb of the HCMV genome (230 kb) were used to construct the
      digoxigenin-11-dUTP-labeled probe which was found to be superior to a total HCMV
      probe representing the entire genome. Crucial hybridization parameters were
      analyzed systematically in order to ensure optimal resolution power and
      sensitivity. The protocol was successfully applied to HCMV-infected fibroblasts
      and peripheral blood leukocytes of 12 transplant patients and unambiguously
      facilitated the precise intracellular localization of HCMV genomes in infected
      cells. Because of its excellent resolution properties, accompanied by the virtual
      absence by any background staining, we recommend the use of this protocol as a
      sensitive approach for further virological analyses of the interactions between
      HCMV and peripheral blood leukocytes at the single-cell level.

PMID- 8877385
TI  - Ontogeny of GTP-binding proteins, Gi and G(o), in rat retina.
AB  - The distribution and the levels of Gi1 (plus Gi3), Gi2, and G(o) in rat retina
      were studied immunohistochemically and immunochemically during development. At
      embryonic day (E) 15, Gi1 alpha/Gi3 alpha was observed in the inner layer of the
      neural retina, the future nerve fiber layer (NFL), while Gi2 alpha was observed
      both in the inner and outer layers of the neural retina. No immunoreactivity for
      G(o) alpha was observed. At E18, Gi1 alpha/Gi3 alpha and Gi2 alpha appeared in
      the inner plexiform layer (IPL), while G(o) alpha was faintly immunoreactive only
      in the NFL. At birth, Gi2 alpha/Gi3 alpha and G(o) alpha appeared in the ganglion
      cell layer. Gi2 alpha was intensely immunoreactive in the NFL and IPL. At
      postnatal day (P) 10, the inner portions of the retina, from the NFL to the outer
      plexiform layer, were immunoreactive to Gi1 alpha/Gi3 alpha, Gi2 alpha, and G(o)
      alpha. Gi1 alpha/Gi3 alpha and G(o) alpha were distributed characteristically in
      a laminated pattern in the IPL, but Gi2 alpha was present homogeneously in the
      IPL. At P12, Gi2 alpha appeared in the outer nuclear layer. As the postnatal days
      advanced, the laminated pattern of immunoreactivity to G(o) alpha in the IPL
      became diffuse, but immunoreactivity to Gi1 alpha/Gi3 alpha remained. The results
      of enzyme immunoassays showed that the concentration of G(o) alpha increased
      rapidly from P10 to P15 and reached almost the adult level at P20-P30, while Gi2
      alpha decreased until P15 and was almost constant thereafter. These results
      showed that the distribution of Gi1 alpha/Gi3 alpha, Gi2 alpha, and G(o) alpha
      differs during development, suggesting that each G protein in the developing
      retina has a unique function.

PMID- 8877386
TI  - Analysis of DNA and morphometry in breast carcinoma.
AB  - Feulgen-stained imprints and smears from 730 cases of invasive breast cancer were
      investigated using an image analysis system. From each tumor sample 100 cells
      were randomly scanned and several DNA and morphometrical parameters evaluated.
      Their prognostic value for a prediction of distant metastases within 5 years was
      investigated with the multivariate Cox regression analysis, which was performed
      for all consecutive cases, as well as for node-negative and node-positive
      patients separately. The multivariate analyses showed a strong prognostic value
      of the anisonucleosis (variation of nuclear radius) and the DNA histogram type in
      addition to the nodal status, the tumor size (pT), and the histological tumor
      grade. However, performing this analysis for both node-positive patients and for
      those without lymph node metastases demonstrated a different prognostic meaning
      of the variables. The combination of each of the group-specific variables led to
      a prognostic factor, which allowed an assignment of patients to several subgroups
      with significantly different risk for distant metastases. Thus, both a low-risk
      group of node-negative patients with a 5-year distant recurrence rate of only
      5.8%, and a higher risk group of node-negative patients with a recurrence rate of
      38.6% could be identified. Among the node-positive patients, a low-risk group
      with a distant recurrence rate of 8.6%, and also a high risk group with 69%
      distant recurrence, could be identified.

PMID- 8877387
TI  - Expression of the mouse testicular histone gene H1t during spermatogenesis.
AB  - The testicular H1 histone variant, H1t, is synthesized during spermatogenesis in
      mammalian male germ cells. In situ hybridization and immunohistochemical
      techniques were used to assign the expression of either the H1t mRNA or the H1t
      protein to specific cell stages of spermatogenesis. Our results show the presence
      of the H1t mRNA only in the late and mid-pachytene stages, whereas the protein
      occurs first in pachytene spermatocytes, and persists until later stages from
      round up to elongated spermatids.

PMID- 8877388
TI  - Evaluation of five green fluorescence-emitting streptavidin-conjugated
      fluorochromes for use in immunofluorescence microscopy.
AB  - Fluorescein isothiocyanate (FITC) is largely used in immunofluorescence methods.
      We propose to analyse the quality of some recent fluorochromes using image
      analysis. Fluorochromes tested include FITC and dichlorotriazinylaminofluorescein
      (DTAF), dipyrrometheneboron difluoride (BODIPY), Rhodol Green and cyanine 2.
      RAMOS cells were immunolabelled against the proliferating cell nuclear antigen
      (PCNA) revealed by the biotin-streptavidin technique. Slides were mounted in
      anhydrous glycerol or in buffered glycerol (pH 7.0 or pH 8.5). No antifading
      medium was added. Cell fluorescence emission intensity and bleaching
      characteristics were measured. Rhodol Green exhibited the highest fluorescence
      intensity and the best photobleaching resistance. Although BODIPY also resisted
      well during the photobleaching assay, its fluorescence intensity was weak. FITC,
      DTAF and cyanine 2 showed intermediate fluorescence intensity and a fast decay of
      fluorescence. Among the green emitting fluorochromes tested, Rhodol Green
      appeared to be the best.

PMID- 8877390
TI  - Cyclophosphamide-induced immunological tolerance: an overview.
AB  - A cyclophosphamide (CP)-induced tolerance system in mice that primarily consists
      of donor cell injection followed by CP-treatment was found useful for inducing a
      long-lasting allo- or xeno-tolerance to various solid organs. In the cells
      followed-by-CP system, the sequential mechanisms of tolerance were clarified
      using the specific correlation between superantigens and certain T cell receptor
      (TCR) V beta segments. Those include the clonal destruction of antigen-stimulated
      mature T cells, the peripheral clonal deletion associated with peripheral
      chimerism, the intrathymic clonal deletion associated with intrathymic chimerism,
      and the clonal anergy. The generation of suppressor T cells was another important
      mechanism of tolerance in the late stage. Special care was taken to overcome the
      " hard" barriers of allo- or xeno-combinations by reducing the "split tolerance"
      produced through the clonal destruction mechanism. For this purpose, the
      tolerogen, antimitotic drugs, their doses, timing, route of administration,
      combined immunosuppressants, and supportive treatment were all crucial for
      successful induction of a long-lasting skin tolerance. This system may be
      applicable to human transplantation.

PMID- 8877389
TI  - Histochemical localization of carbonic anhydrase in the trachea of the guinea
      pig.
AB  - Tissue specimens from guinea pigs were examined using an enzyme-histochemical
      reaction to explore the presence of carbonic anhydrase (CA) activity in the
      trachea. CA activity was detected in a group of morphologically distinct
      epithelial cells, in goblet cells, and in glands of the tracheal mucosa. The
      epithelial cells showing CA activity were distributed singly and sparsely
      throughout the entire trachea. These cells showed a wide morphological
      variability and were clearly different from those forming the pseudostratified
      ciliated epithelium. Their number was higher in sections closer to the tracheal
      bifurcation than in those near the larynx. Although the nature of these cells is
      unknown, based on their morphological and histochemical characteristics and their
      distribution, they may represent a specialized chemoreceptor. To our knowledge,
      this is the first report of CA localized in tracheal epithelial cells.

PMID- 8877391
TI  - Expression of activation-related molecules on regional lymph node lymphocytes in
      human lung cancer.
AB  - Using two- and three-color flow cytometry, we investigated the surface makers of
      regional lymph node lymphocytes (RLNL) in 54 patients with primary lung cancer in
      order to determine whether or not RLNL are in an activation state when compared
      with the corresponding peripheral blood lymphocytes (PBL) for the purpose of
      clarifying the characteristics of RLNL. RLNL showed a cell composition that was
      different from the corresponding PBL with a high proportion of CD3+ cells, CD4+
      cells and CD20+ (B) cells as well as a low proportion of CD8+ cells and CD16+
      (NK) cells. RLNL also contained a significantly higher proportion of CD45RO+ T
      cells and a lower proportion of CD45RA+ T cells in comparison to the
      corresponding PBL. Furthermore, we explored the activation-related molecules such
      as the interleukin-2 receptor (IL-2R) alpha chain, the IL-2R beta chain, HLA-DR
      and leukocyte function-associated antigen 1 (LFA-1) on CD4+ and CD8+ cells. The
      data showed that the expression of CD45RO, the IL-2R alpha chain, HLA-DR on CD4+
      cells, and those of CD45RO and HLA-DR on CD8+ cells were significantly higher in
      RLNL than in PBL. On the other hand, PBL showed a higher expression of the IL-2R
      beta chain and LFA-1 only on CD8+ cells, which are thought to include CD8+ NK
      cells. When these activation related molecules were analyzed on CD45RO+ T cells,
      which are thought to be memory T cells, then the expression of the IL-2R alpha
      chain, HLA-DR on CD4+CD45RO+ cells and HLA-DR on CD8+CD45RO+ cells were
      significantly higher in RLNL than in PBL. Lastly, we analyzed the surface
      molecules according to such clinical factors as metastasis to the lymph nodes and
      the stage of lung cancer. Interestingly, RLNL with lymph node metastasis showed
      an increase in the percentage of CD20+ cells and a decrease in the percentage of
      CD4+ cells in comparison to those with benign lung disease, while these
      differences were not observed in PBL. The expression of ++CD45RO and LFA-1 on
      CD4+ and LFA-1 on CD8+ cells on RLNL in stage I + II is significantly higher in
      comparison with benign lung disease. Furthermore, RLNL in stage III + IV revealed
      the reduced expression of CD45RO, HLA-DR and LFA-1 on both CD4+ and CD8+ cells
      compared with those in stage I + II. These results thus demonstrated that RLNL
      were in a more activated state, particularly in stages I + II, than PBL. Whether
      these activation states in RLNL are directed against autologous tumor cells or
      not can hopefully be elucidated after the completion of further ongoing studies.

PMID- 8877392
TI  - Unrepresentative behavior of T cell receptor-transgenic CD4+ T cells upon
      adoptive transfer: lack of need for priming and an extended booster dose
      response.
AB  - The response of CD4+ T cells taken from DO11.10 alpha beta TCR-transgenic mice to
      their specific antigen, ovalbumin, was examined in an adoptive transfer system.
      Read out was the % frequency of KJI-26.1+ (clonotype positive) cells within the
      Thy-1.2+ (T cell) population in lymph nodes. Control experiments indicated that
      these cells were uniformly CD4+. Immunizing the transgenic mice had no detectable
      effect on this frequency. Furthermore, the frequency in recipients of adoptively
      transferred lymph node cells was not affected by priming of the donors with
      ovalbumin by various procedures. Transfers were into syngeneic SCID recipients,
      except in one experiment, where irradiated recipients were shown to behave in the
      same way. Examining the effect of varying the amount of booster antigen, the
      response increased slowly with dose, up to a plateau in the range of 10-100 mg
      ovalbumin. The lack of need for priming is unusual, in comparison with an
      adoptive transfer of non-transgenic cells, as is the extended dose response range
      with such a high optimum dose. This enhanced responsiveness is interpreted in
      terms of a lack of down-immunoregulation in these transgenic mice.

PMID- 8877393
TI  - Immunosuppression by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies of free and
      vascularized skin allograft rejection.
AB  - Immunosuppression by anti-adhesion molecule antibody of free or vascularized skin
      allograft rejection was investigated in rats. Lewis (LEW, RT11) rats were used as
      donors and Fisher (F344, RT11v1) rats as the recipients. When F344 rats were
      treated intraperitoneally (i.p.) with anti-intercellular adhesion molecule-1
      (ICAM-1) mAb (1A29) (3 mg/kg/day) and anti-leukocyte function-associated antigen
      1 (LFA-1) mAb (WT.1) (3 mg/kg/day) one day prior to grafting and daily after
      grafting for nine days, free skin graft survival was prolonged only slightly
      compared with that in control rats which were injected i.p. with a daily dose of
      6 mg/kg of anti-TNP mAbs (H1-6-2) one day prior to grafting and daily after
      grafting for nine days. (Mean survival time [MST] of the free skin graft was 11.2
      +/- 0.6 days in the control group and 13.4 +/- 0.3 days in the 1A29 + WT-1
      treated group [p < 0.01], respectively.) On the other hand, the vascularized
      graft survival was prolonged significantly in anti-ICAM-1/LFA-1 mAbs-treated F344
      rats as compared with that in control rats. (The mean vascularized graft survival
      time was 14.2 +/- 0.7 days in the control group and 21.5 +/- 1.9 days in 1A29 +
      WT-1 treated group [p < 0.002]). Our results suggest that interaction with ICAM-1
      and LFA-1 is more important in the rejection of vascularized skin allografts than
      that of free skin allografts.

PMID- 8877394
TI  - The opposite effect of tumor-infiltrating natural killer cells on in vivo priming
      of tumor-specific CD8+ T cells and CD4+ T cells.
AB  - Natural killer (NK) cells, which infiltrated the tumor site, were examined for
      their effects on the in vivo priming of tumor-specific CD8+ and CD4+ T cells.
      CD8+ T cells were responsible for the activity of B16 melanoma-specific cytotoxic
      T lymphocytes (CTL). The in vivo depletion of NK cells with anti-NK1.1 monoclonal
      antibody (mAb), prior to B16-immunization, significantly decreased the capacity
      of the spleen cells (s.c.) to generate B16-specific CTL after in vitro
      restimulation. However, the CD8+ T cells of the s.c. from NK cell-depleted and
      subsequently B16-immunized mice increased their potential to become B16-specific
      CTL compared with those from the B16-immunized mice. The tumor-infiltrating NK
      cells showed a low but significant degree of CTL activity against B16. In
      addition, the disrupted B16 melanoma cells demonstrated less of an ability to in
      vivo prime the tumor-specific CD8+ T cells. These findings thus suggest the
      possibility that the quick disruption of tumor cells by tumor-infiltrating NK
      cells consequently interfered with the in vivo priming of the tumor-specific CD8+
      T cells. On the other hand, the CD4+ T cells of the s.c. from NK cell-depleted
      and subsequently B16-immunized mice showed less of a capacity to induce the tumor
      specific CTL compared with those from B16-immunized mice. In addition, the
      delayed-type hypersensitivity response against B16 was significantly diminished
      by the in vivo depletion of NK cells prior to B16-immunization. These findings
      thus suggest that NK cells have a promoting effect on the in vivo priming of CD4+
      T cells. Overall, however, our findings indicate that early-appearing tumor
      infiltrating NK cells have an opposite effect on the in vivo priming of CD8+ and
      CD4+ T cells.

PMID- 8877395
TI  - Monoclonal nonspecific suppressor factor beta (MNSF beta) inhibits the production
      of TNF-alpha by lipopolysaccharide-activated macrophages.
AB  - The monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by a
      murine T cell hybridoma, shows a pleiotropic antigen-nonspecific suppressive
      function. Most recently, a cDNA encoding a subunit of MNSF (MNSF beta) has been
      isolated and characterized. Recombinant form of MNSF beta (rMNSF beta) inhibits
      lymphokine functions, as does native MNSF. In this study, we investigated whether
      rMNSF beta also affects macrophage function in terms of LPS-induced TNF-alpha
      production by a mouse macrophage cell line, J774. rMNSF beta suppressed the TNF
      alpha production in a dose-dependent manner. This suppressive effect was
      remarkably reduced when rMNSF beta was added after 6 h of LPS stimulation. In
      addition, enhancement of TNF-alpha production by IFN-gamma was also suppressed by
      rMNSF beta. The suppressive effect was partly neutralized by the addition of the
      serine/threonine phosphatase inhibitor, okadaic acid. This finding suggests that
      serine/threonine protein phosphatases type 1 and/or 2A may be implicated in the
      mechanism of action of MNSF.

PMID- 8877396
TI  - The proliferation of human T lymphocytes stimulated by Helicobacter pylori
      antigens.
AB  - Fractionated mononuclear cells (MNCs) were obtained from peripheral blood of
      healthy human volunteers, seronegative for H. pylori antibodies. The MNCs were
      stimulated in culture with whole live or heat-killed H. pylori cells or with
      bacterial cell surface (SA) or cytoplasmic (CA) antigens. There was a marked
      proliferative response of T cells in cultures stimulated with 10(5) cells/well of
      live H. pylori, 5 micrograms/well of CA or 5-20 micrograms/well of SA. However,
      no proliferation was observed in MNC cultures containing higher "doses" of live
      H. pylori organisms (10(7)/well) or CA (20 micrograms/well). Moreover, higher
      "doses" of the bacteria or CA entirely inhibited the response of T cells to PHA.

PMID- 8877397
TI  - Increased plasma concentrations of circulating intercellular adhesion molecule-1
      (cICAM-1) in patients with necrotizing pancreatitis.
AB  - The intercellular adhesion molecule-1 (ICAM-1), a membrane glycoprotein, is
      important in the adhesion of cytokine-stimulated leukocytes to the endothelium of
      microvessels and their transendothelial migration. Circulating isoforms of ICAM-1
      (cICAM-1) are known to be elevated in human serum as an indirect consequence of
      inflammatory responses. The aim of this study was to investigate whether cICAM-1
      levels are elevated in patients with acute pancreatitis within 48 h of the onset
      of abdominal pain and whether cICAM-1 levels correlate with the severity of the
      tissue damage. Twenty-five consecutive patients admitted to a medical ICU had
      elevated cCAM-1 concentrations of 548 +/- 68 ng/ml, significantly different when
      compared to a control group of 18 healthy subjects (343 +/- 29; p = 0.018).
      According to the findings of contrast-enhanced CT or laparotomy patients were
      further divided in a group with acute edematous pancreatitis and a group with
      acute necrotizing pancreatitis. Pancreatic necrosis was associated with cICAM-1
      levels of 729 +/- 106 ng/ml, significantly different from patients with mild
      disease (367 +/- 48) and controls (p < 0.001). Plasma cICAM-1 levels were not
      significantly different between healthy subjects and patients with mild
      pancreatitis. A significant correlation was found between cICAM-1 and C-reactive
      protein, an acute phase reactant and marker of necrotizing pancreatitis (r =
      0.62; p < 0.01). The sensitivity and specificity for the detection of edematous
      or necrotizing pancreatitis of cICAM-1 plasma concentrations (cutoff point at 500
      ng/ml) were 75% and 85%, respectively. These results suggest an enhanced release
      of ICAM-1 into plasma in the early stage of acute necrotizing pancreatitis.
      Leukocyte-endothelial cell adhesion may be associated with the inflammatory
      process of necrotizing tissue damage in acute pancreatitis. It could thus serve
      as a marker or predictor of a severe clinical course of pancreatitis.

PMID- 8877398
TI  - Anti-candidial activity of natural killer (NK) and lymphokine activated killer
      (LAK) lymphocytes in vitro.
AB  - The natural cytotoxic effects of peripheral blood lymphocytes (PBL) on Candida
      stellatoidea and several other Candida species were examined by a colony forming
      inhibition (CFI) assay. Peripheral blood mononuclear cells (PBMC), were incubated
      with C. stellatoidea yeast cells. After the incubation period the colony-forming
      ability of the yeast was significantly reduced. In similar experiments, six
      different Candida species (C. albicans, C. krusei, C. stellatoidea, C.
      tropicalis, C. pseudotropicalis, C. guillermondii) were used as target cells.
      There was no statistically significant difference in the anticandidial activities
      of PBL against the Candida species used. It was demonstrated that a fraction of
      lymphocytes, natural killer cells (NK), had the major natural anti-candidial
      activity by using anti-Leu M1 (CD 15) and anti-Leu 11b (CD 16) monoclonal
      antibodies (mAbs) plus complement (C'). It was observed that inhibition of colony
      forming ability of C. stellatoidea was significantly (78-96%) reduced when anti
      Leu 11b plus C' were used. In addition, the colony formation inhibition capacity
      of NK cells was increased by recombinant human interleukin-2 (rhIL-2) while anti
      interferon-gamma (IFN-gamma) had no effect. Besides the fact that NK cells are
      among those responsible for natural immunity against Candida species, this colony
      forming inhibition assay performed with C. stellatoidea yeast cells as target and
      monocyte-depleted PBMC as effector cells, is a simple method to assess NK cell
      activity.

PMID- 8877399
TI  - Brefeldin A inhibits antigen- or calcium ionophore-mediated but not PMA-induced
      phospholipase D activation in rat basophilic leukemia (RBL-2H3) cells.
AB  - Recent reports have indicated that ADP-ribosylation factor (ARF) plays a role in
      the regulation of phospholipase D (PLD) activity in the in vitro assay system.
      Since a fungal metabolite brefeldin A (BFA) is known to interfere with ARF
      function, the effect of BFA on antigen-induced PLD activation was examined in rat
      basophilic leukemia (RBL-2H3) cells. BFA inhibited the antigen-induced formation
      of phosphatidylbutanol (PBut), a specific and stable metabolite produced by PLD
      activity in a concentration-dependent manner. The maximal inhibition obtained at
      10 micrograms/ml of the drug was nearly 70% and further inhibition was not
      observed at higher concentrations. Ca(2+)-ionophore A23187-mediated PLD
      activation was also prevented by BFA. In contrast, BFA failed to inhibit PLD
      activation in response to 4 beta-phorbol 12-myristate 13-acetate (PMA), an
      activator of protein kinase C (PKC). This indicates that there are BFA-sensitive
      and BFA-insensitive pathways leading to PLD activation in RBL-2H3 cells and also
      that the PKC-mediated pathway may be insensitive to BFA treatment, suggesting the
      existence of PLD isozymes. BFA inhibited Ag-induced serotonin release at a
      concentration 20-fold lower than that needed for the inhibition of PLD. Moreover,
      PMA caused a marked production of PBut, but it failed to elicit secretory
      response. This implies that PLD may be not a crucial element for secretory
      responses.

PMID- 8877400
TI  - Leishmania major infection in major histocompatibility complex class II-deficient
      mice: CD8+ T cells do not mediate a protective immune response.
AB  - In order to evaluate the role of CD8+ T cells in cutaneous leishmaniasis, major
      histocompatibility complex (MHC) class II-deficient mice of C57BL/6 background
      lacking functional CD4+ T cells were infected with Leishmania major. In contrast
      to C57BL/6 wild-type mice which are resistant to infection with L. major, these
      mice developed severe skin lesions that did not heal. In comparison to
      susceptible BALB/c mice, however, lesion development in MHC class II-deficient
      mice was very much retarded, even though the increase in the parasite load in
      lymphoid organs was only slightly delayed. Lymph node cells from L. major
      infected MHC class II-deficient mice produced very low levels of interferon-gamma
      upon stimulation with L. major antigen, whereas the response to the mitogen
      concanavalin A was not impaired. Interestingly, they did not release lymphokines
      associated with disease exacerbation (interleukin 4 and interleukin 10) either,
      suggesting that the delayed lesion development is caused by the lack of disease
      promoting CD4+ cells rather than by the presence of protective CD8+ cells. The
      lack of L. major-reactive immunoglobulins in the serum of infected MHC class II
      deficient mice indicates that B cells also cannot respond to parasite antigens in
      the absence of MHC class II-mediated helper signals. The data demonstrate that
      MHC class II-deficient mice are unable to restrict the spreading of L. major,
      although they contain highly increased proportions of CD8+ T cells. Thus, MHC
      class II-restricted immune responses, most likely mediated by functional CD4+ T
      cells, are essential for the control of primary infections with L. major.

PMID- 8877401
TI  - Allogeneic recognition of HLA-DRB1*0406 by T cells with HLA-DRB1*0403: role of
      amino acid residue 37 on the beta sheet in T cell recognition.
AB  - Five T cell clones reactive with allogeneic HLA-DR molecules were obtained by
      stimulating CD4+ T cells (DRB1*0403) with DRB1*0406-homozygous KT13 cells whose
      DR beta chain differed by a single amino acid residue (37) on the beta sheet from
      the DRB1*0403 product. Except for one T cell clone which had both auto- and
      alloreactivities, these clones proliferated by stimulation with KT13 but not with
      autologous cells, indicating that the single substitution at position 37 on the
      HLA-DR molecule was sufficient to alter the alloantigenicity of the DR molecule
      and to elicit an allogeneic T cell response. Two clones reacted with some but not
      all B cell lines with DRB1*0406, suggesting the possible involvement of a certain
      peptide whose distribution is restricted to some cells which form the
      alloantigenic structure recognized by these clones. The two remaining clones
      showed broad but distinct anti-DR specificity in addition to anti-DRB1*0406
      reactivity, suggesting that they recognize the DRB1*0406-peptide complex whose
      antigenic structures also occur in some combinations of other DRB1 alleles with
      certain peptides bound to these alleles. The T cell clone with both auto- and
      alloreactivity was found to react with autologous monocytes but not with
      autologous B or T cells and to express lower TCR alpha beta than other T cell
      clones which showed no autoreactivity. The possible recognition molecule for this
      autoreactive T cell clone is discussed.

PMID- 8877402
TI  - Immunosuppressive activity of bovine seminal ribonuclease and its mode of action.
AB  - Two preparations of dimeric BS RNase-native and recombinant proteins caused
      identical immunosuppressive effects on MLC-stimulated human lymphocytes. The
      monomers of RNase A and BS RNase were ten times less active. The inhibitory
      effect on MLC-stimmulation was followed by 90% inhibition of cell-mediated
      lympholysis (CML) caused by BS RNase (10 micrograms/ml). This effect indicated
      that BS RNase suppressed the recognition phase of the cytotoxic reaction,
      resulting in inhibition of generation of cytotoxic effector cells. BS RNase
      exerted a similar effect on generation of cytotoxic LAK cells. Cytotoxic activity
      of LAK cells or CTLs against K562 target cells was abrogated only when BS RNase
      was added at the beginning of the sensitizing phase, but the cytotoxicity of
      effector cells in the destruction phase was not influenced. The effect of RNase A
      on the generation of cytotoxic cells was much less pronounced. To get more
      information about the site of action, the effect of BS RNase on early lymphocyte
      stimulation by PHA was investigated by using fluorescein cell probes. BS RNase
      (100 micrograms/ml) prevented a shift in fluorescein emission occurring within
      one hour of activation using fluorescein diacetate as a marker for changes in the
      cytoplasmic matrix. On the contrary, it did not block the shift in fluorescence
      emission when tested with diphenylhexatrien as a marker for changes in membrane
      fluidity. Furthermore the effect of BS RNase on expression of membrane antigens
      expressed on activated human lymphocytes was estimated. BS RNase significantly
      inhibited the expression of CD25, CD38 and CD71 antigens on PHA-, Con A- and MLC
      stimulated human T and B lymphocytes. No substantial change in expression of
      these antigens was observed on IL-2-stimulated cells, but DNA synthesis was
      totally abrogated. These results indicate that the mode of action of BS RNase on
      activated T and B lymphocytes is based mainly on the suppressed expression of
      receptors for interleukin-2-alpha-chain and transferrin.

PMID- 8877403
TI  - The role of MHC class I expression in rat NK cell-mediated lysis of syngeneic
      tumor cells and virus-infected cells.
AB  - In this study the role of MHC class I antigen expression in rat natural killer
      (NK) cell-mediated lysis was investigated. Various rat tumor cell lines and two
      Adenovirus (Ad)-transformed rat cell lines were tested for their expression
      levels of total MHC class I and two MHC class I alleles, RT1.A and RT1.C, by flow
      cytometry. Their susceptibility to NK cell-mediated lysis in relation to MHC
      class I expression was determined by 51Cr release assays. IFN-gamma is know to
      increase the expression of MHC class I. Therefore target cell with and without
      prior IFN-gamma treatment were examined for MHC class I expression and its effect
      on NK lysis. An significant inverse exponential relationship was found. To
      investigate the effect of virus infection on MHC class I expression and target
      cell lysis by NK cells, rat embryonal fibroblasts (REF) were infected with
      cytomegalovirus (CMV) and used as target cells for NK cell-mediated lysis.
      Results showed that these virus-infected cells were less susceptible to NK lysis
      than non-infected cells. Moreover, the non-infected cells expressed less MHC
      class I than the infected cells, indicating that also in this case, there was an
      inverse correlation between MHC class I expression and susceptibility to lysis by
      NK cells. Subsequently, we showed that sorted subsets of predominantly CD8
      positive and CD8-negative NK cells lysed a MHC class I-positive tumor cell line
      at the same level. This suggests that CD8 is not likely to participate as a
      receptor for MHC class I in NK cell-mediated lysis in a syngeneic rat model.

PMID- 8877404
TI  - Effects of macrophage colony-stimulating factor (M-CSF) on lipopolysaccharide
      (LPS)-induced mediator production from monocytes in vitro.
AB  - M-CSF is a macrophage-lineage-specific growth factor that causes proliferation
      and differentiation of progenitor cells in the bone marrow. To investigate the
      effects of M-CSF on more matured cells, human monocytes were cultured in the
      presence or absence of M-CSF for 6 days. Addition of M-CSF at more than 10(2)
      U/ml resulted in higher viability and caused morphological differentiation to
      large macrophage-like cells. LPS-induced mediator production was also compared
      between M-CSF-treated and control cell. Monocytes were incubated with or without
      M-CSF for 3 days, and were stimulated with 1 microgram/ml of LPS for 2 days. IL-1
      beta was not detected in the both culture supernatants, and PGE2 production was
      not influenced by M-CSF. However, amounts of G-CSF, GM-CSF, IL-6, and TNF-alpha
      produced in response to 1 microgram/ml of LPS were 1.5 to 2 times greater from
      monocytes treated with 10(4) U/ml of M-CSF than from control cells. The priming
      effect of M-CSF on LPS-induced cytokine production was found to require 3-day
      preincubation, and reached a maximum at the concentration of 10(4) U/ml. M-CSF
      treated cells responded to a 10 times lower concentration of LPS than control
      cells in terms of cytokine production. M-CSF was also shown by flowcytometric
      analysis to influence the expression of CD14, a receptor for LPS, which might
      render monocytes more sensitive to LPS.

PMID- 8877405
TI  - Streptococcal erythrogenic toxins induce neopterin formation in human peripheral
      blood mononuclear cells but not in the human myelomonocytoma cell line THP-1.
AB  - We tested whether the exposure of human monocytic cells to streptococcal
      erythrogenic toxins A, B, C and a streptococcal-derived Mitogert BX is associated
      with synthesis of neopterin in vitro. Neopterin production was not induced when
      the human myelomono-cytoma cell line THP-1 was stimulated with these toxins, and
      there was only a slight co-stimulatory effect of streptococcal erythrogenic toxin
      A together with interferon-gamma stimulation. However, these toxins induced
      interferon-gamma and further neopterin production in peripheral blood mononuclear
      cells of three healthy individuals. This neopterin formation could be blocked by
      anti-human interferon-gamma. From our investigations we conclude that there is no
      direct effect of streptococcal erythrogenic toxins on neopterin production by
      monocytic cells. However, the data obtained in peripheral blood mononuclear cell
      culture imply that these toxins are able to stimulate neopterin production in
      humans via the induction of huge amounts of interferon-gamma.

PMID- 8877406
TI  - Monocyte-derived macrophages prime peripheral T cells to undergo apoptosis by
      cell-cell contact via ICAM-1/LFA-1-dependent mechanism.
AB  - We designed the present study to clarify the mechanism of superantigen-induced
      apoptosis of human mature T cells and to elucidate the pivotal roles of monocyte
      derived macrophages in induction of T cell apoptosis. Exposure of unfractionated
      human peripheral blood mononuclear cells to SEA, SEB or PHA elicited apoptosis in
      T cells after 5-day culture. In purified T cell preparations, SEB was unable to
      induce apoptosis, but was inductive when the purified T cells were cocultured
      with monocyte-derived macrophages adhering to plastic culture dishes. Placing the
      T cells in the insert wells which physically separated them from the adhering
      macrophages resulted in a complete loss of SEB-induced apoptosis. The addition of
      blocking antibodies against LFA-1, ICAM-1 and CD2 to the cocultures significantly
      inhibited the SEB-induced T cell apoptosis. We concluded therefore that direct
      contact of macrophages with T cells is critical in SEB-induced T cell apoptosis,
      and that adhesion molecules such as LFA-1/ICAM-1 and CD2 may be involved in the
      mechanism of this effect.

PMID- 8877407
TI  - Complement activation by myeloperoxidase products released from stimulated human
      polymorphonuclear leukocytes.
AB  - Purified human myeloperoxidase (MPO) converted human C5 to an activated form,
      i.e. the C5 protein adopted a configuration expressing a binding site for C6; the
      resulting C56 complex then reacted with C7, C8 and C9 forming a hemolytic C5-9
      complex. For the activation by myeloperoxidase chloride and hydrogen peroxide
      were essential. This indicates that the peroxidase acted through the generation
      of HOCl which had been shown earlier to oxidize and activate C5. Human
      polymorphonuclear leukocytes (PMN) were stimulated in vitro by incubation with
      opsonized zymosan; thereafter the supernatants were tested for C5 activating
      potency. Stimulated PMN release H2O2 and MPO that produces hypochlorite and
      secondarily various chloramines. As a trap for the labile hypochlorite generated
      excess taurine was added to the PMN suspensions during the incubation.
      Hypochlorite is then stoichiometrically converted to the relatively stable
      taurine chloramine. In order to rule out interfering activities of proteolytic
      enzymes released from the PMN and known to attack C5, the supernatants were
      ultracentrifuged, and the ultrafiltrates, containing only low molecular weight
      compounds, were used for the further studies. They contained taurine chloramine,
      estimated photometrically, and they activated C5 upon incubation, assayed
      functionally by reactive lysis. Azide, an inhibitor of myeloperoxidase, and
      catalase which destroys H2O2, essential for MPO-catalyzed oxidations, prevented
      the generation of C5 activating potency and of chloramines. Unstimulated PMN
      produced neither oxidants nor C5 activating potency. When taurine was omitted
      from the PMN suspensions during stimulations much less oxidant was found in the
      supernatants and less C5 activating potency. These findings indicate that the C5
      activating agent was produced by stimulated PMN through MPO-generated
      hypochlorite, trapped as taurine chloramine. In the absence of added taurine the
      hypochlorite formed by MPO oxidized endogenous amines that also activated C5.
      Further studies suggested that among these was some monochloramine derived from
      endogenous ammonia. Activation of the terminal complement reaction sequence by
      MPO released from stimulated PMN may represent a third pathway to complement
      activation contributing to and reinforcing complement and PMN functions at the
      site of inflammation or tissue injury.

PMID- 8877408
TI  - Phenylarsine oxide (PAO)-mediated activation of phospholipase D in rat basophilic
      leukemia (RBL-2H3) cells: possible involvement of calcium and protein kinase C.
AB  - Addition of phenylarsine oxide (PAO) to [3H]oleic acid-labeled rat basophilic
      leukemia (RBL-2H3) cells gave rise to the remarkable formation of
      [3H]phosphatidylbutanol (PBut), a specific product of phospholipase D (PLD)
      activation. Preincubation of cells with 2,3-dimercaptopropanol (DMP) or
      dithiothreitol (DTT), compounds containing sulfhydryls, prevented PAO-stimulated
      [3H]PBut formation, indicating that PAO-stimulated PLD through interacting with
      vicinal thiol groups. Treatment of cells with PAO resulted in increase in
      intracellular Ca2+ concentration without significant production of inositol
      phosphates. Removal of extracellular free Ca2+ by chelating with EGTA was found
      to inhibit [3H]PBut formation by PAO. Incubation of cells with 20 nM phorbol 12
      myristate 13-acetate (PMA) for 6 h caused down-regulation of protein kinase C
      (PKC) alpha and beta isozymes, whereas it had no effect on PKC delta, epsilon and
      zeta isozymes. Under this condition, decrease in PAO-stimulated [3H]PBut
      formation was observed to occur with a concomitant decrease in the level of PKC
      alpha and beta isozymes. These results suggest that a covalent bridge between
      vicinal thiol groups of cell surface proteins induced by PAO potentiates PLD
      activation and that PAO-induced PLD activation is regulated by Ca2+ and PKC alpha
      and/or beta isozymes.

PMID- 8877409
TI  - A promising model of primary human immunization in human-scid mouse.
AB  - The engraftment of human peripheral blood mononuclear cells (Hu-PBMC) from adult
      donors in scid mice has been published by MOSIER et al. in 1988. The possibility
      to obtain a secondary human immune response in human-scid mice has also been
      reported but attempts to induce a primary human immune response still remain
      difficult to achieve. In this work, an antigen (Canine albumin) or a hapten (DNP)
      was coupled with tetanus toxoid, an antigenic protein against which our human
      donors already had memory T cells through vaccination. In this way, hu-scid mice
      immunized with coupled DNP-tetanus toxoid (TT-DNP) or coupled Canine albumin
      Tetanus toxoid (Calb-TT) mounted a specific human immune response anti-DNP or
      anti-Canine albumin (Calb) respectively. A secondary human immune response anti
      tetanus toxoid was also detected in the sera of hu-scid mice immunized with
      product containing TT but not in the sera of those injected with PBS alone. The
      scid mice grafted with Hu-PBMC from a TT naive donor and challenged with Calb-TT
      or Calb alone failed to produce specific anti-Calb antibodies. These observations
      demonstrate that memory T cells can give a substantial help to naive B cells
      which interact with them for obvious B cell activation and differentiation into
      plasma cells. This model of immunization might be useful for other antigens of
      choice, allowing the production of human monoclonal antibodies, in combination
      with a suitable system of immortalization. Attempts to immunize human cells in
      scid mice against DNP coupled to LO-BM2 (a rat monoclonal antibody anti-human
      IgM) failed to induce a specific human response either anti-rat immunoglobulins
      (Igs), or anti-DNP and led to a decrease of human Ig production in hu-scid. We
      also immunized hu-scid mice against ovalbumin alone but, only in some cases, a
      low specific human immune response was observed, so this system seems to be
      unreliable.

PMID- 8877410
TI  - CD4 expression is important but not essential for infection with exogenous mouse
      mammary tumor virus.
AB  - We studied local events in the popliteal lymph nodes of CD4-deficient mice
      following foot pad injection with an MMTV strain which carries the gene for a V
      beta 14-specific superantigen. Injection of the V beta 14-specific MMTV induced
      vigorous expansion of V beta 14+ CD4+ T cells and B cells in their lymph nodes of
      CD4+/- heterozygous control mice. On the other hand, CD4-/- mice injected with
      the MMTV showed a proliferation of V beta 14+ T cells among the population of TCR
      alpha beta + CD4-CD8- T cells, although to a lesser extent. This phenomenon was
      not accompanied by vigorous B cell expansion. A PCR assay revelated that the MMTV
      definitely infected the lymph nodes cells of the CD4-/- mouse. However, the
      infectivity of the MMTV in CD4-/- mice was approximately 20 times lower than that
      in CD4+/- mice. These findings indicate that, in MMTV infection of CD4-deficient
      mice, the superantigen-reactive T cells among the population of TCR alpha beta
      +CD4-CD8- T cells substitute for the superantigen-reactive CD4- T cells of normal
      mice, and that the absence of CD4 molecules decreased the infectivity of MMTV
      because of insufficient expansion of the superantigen-reactive T cells.

PMID- 8877411
TI  - Induction of nitric oxide synthase in bovine mononuclear phagocytes is
      differentiation stage-dependent.
AB  - Bovine monocytes and monocyte-derived macrophages (MDM) activated by various
      means were assessed for induction of inducible nitric oxide synthase (iNOS),
      using the Griess assay, Northern blotting and reverse transcription/polymerase
      chain reaction (RT-PCR). Interferon-gamma (IFN-gamma) induced little, if any,
      iNOS expression and NO production in MDM, although these cells responded to IFN
      gamma in other regards. In contrasts, MDM produced copious amounts of NO when
      stimulated with LPS or Salmonella dublin, and this was paralleled by high steady
      state levels of iNOS mRNA. Heat-killed Listeria monocytogenes induced more iNOS
      mRNA and nitrite than IFN-gamma, but much less than L. mono-cytogenes and IFN
      gamma combined. Monocytes differed from M phi with respect to iNOS induction and
      nitrite production in several regards: (i) LPS and S. dublin induced only low
      levels of iNOS mRNA and nitrite in monocytes, although cells responded to these
      stimuli in various other ways: (ii) IFN-gamma alone induced in monocytes iNOS
      mRNA generation and NO formation, although to a low and variable degree; (iii)
      upon maximal stimulation (e.g. by L. monocytogenes and IFN-gamma combined),
      monocytes produced much less nitrite than MDM, and mRNA levels were lower.
      Regulation of macrophage iNOS varies considerably between species. We provide the
      first evidence in any species that the steady state levels of iNOS mRNA and NO
      generation in monocytes and macrophages activated by various means depend on the
      stage of mononuclear phagocyte differentiation.

PMID- 8877412
TI  - Conformation dependency of nitric oxide synthesis of murine peritoneal
      macrophages by beta-glucans in vitro.
AB  - We have already demonstrated that various activities including NO (nitric oxide)
      synthesis in vivo were significantly different between triple helical (SPG) and
      single helical (alkaline-treated SPG, SPG-OH) beta-glucans, and that beta-glucan
      mediated NO synthesis was associated with increased gene expression of IFN-gamma.
      In this study, we analyzed beta-glucan-mediated NO production in vitro with the
      concomitant use of IFN-gamma. Proteose peptone-elicited peritoneal macrophages
      (PM) were collected from male C3H/HeJ mice and cultured with beta-glucans in the
      presence or absence of IFN-gamma for 24 h. It was found that SPG-OH, but not SPG,
      enhanced NO synthesis in vitro, especially in the presence of IFN-gamma.
      Concentrations of interleukin-1 alpha, -6 and TNF-alpha in the culture
      supernatant of SPG-OH were significantly higher than those in that of SPG.
      Membrane-associated IL-1 alpha was also high with SPG-OH. Cytokine productivity
      of PMs, as well as NO synthesis, was elevated in the presence of IFN-gamma. These
      facts intensely suggest that the single helical conformer of beta-glucan (SPG-OH)
      is dominant in cytokine production and subsequent NO synthesis.

PMID- 8877413
TI  - Purification and primary amino acid sequence of a novel neutrophil chemotactic
      factor LECT2.
AB  - We purified a neutrophil chemotactic factor from a culture fluid of the PHA
      activated human T-cell leukemia SKW-3 cells. The factor showed a 16-kDa basic
      protein by Tricin-SDS-polyacrylamide gel electorophoresis and analysis of amino
      acid composition. The primary amino acid sequence revealed that the chemotactic
      factor was significantly different from other known chemotactic factors,
      indicating a novel protein designated LECT2. The sequence revealed homology with
      the myb-induced myeloid protein-1 (Mim-1), which is expressed from gene in
      immature and normal granulocytes of chicken. Its biological function had not yet
      been identified. LECT2 and Mim-1 may be involved in the regulation of neutrophil
      functions in an as yet unidentified way.

PMID- 8877414
TI  - Embryo associated immunosuppressor factor (EASF) and serum estradiol synergism in
      pre-embryonic development after in vitro fertilization.
AB  - The aim of this study was to test whether the level of serum immunosuppressor
      factor (EASF) and serum estradiol (E2) play a cooperative role in the pre
      implantation early embryonic development in IVF-patients. Serum samples were
      collected from 80 patients undergoing IVF-ET and the level of EASF in patient's
      sera was assayed using a two-site sandwich enzyme linked immunosorbent assay
      (ELISA) system. Two-hundred fifty-one IVF-culture media were obtained from these
      patients and the EASF activity was measured using concanavalin A-induced
      lymphocyte proliferation assay. EASF activity in embryo growth media, quality of
      ova, number of cells in each pre-embryo at the time of embryo transfer, cycle day
      3 serum E2 and peak E2 levels were correlated with pregnancy outcome. Thirty
      three out of 80 patients had detectable levels of serum EASF. The number of pre
      embryos with > 4 cell stage at the time of embryo transfer correlated with the
      total number of ova retrieved in patients positive for serum EASF (P = 0.01) and
      patients that had an ongoing pregnancy at 7-8 weeks (P < 0.01). Ratio of the
      number of pre-embryos with > 4 cell stage at the time of embryo transfer and
      total number of ova retrieved correlated with cycle day 3 serum E2 (P < 0.01) and
      peak E2 (P = 0.01) levels only in patients positive for EASF. The EASF activity
      of embryo growth media correlated with cycle day 3 serum E2 (P = 0.0001) and peak
      E2 (P = 0.007) levels only in patients that were positive for EASF and got
      pregnant after IVF-ET. This study suggests that the levels of serum EASF and E2
      may act synergistically in the development of early embryo.

PMID- 8877415
TI  - Three regions of HIV-1 gp160 contain clusters of immunodominant CTL epitopes.
AB  - HIV-1 infection stimulates a strong CTL response that coincides with resolution
      of viremia in acute infection and declines with development of opportunistic
      infections. Recognition of HIV gp160 by PBMC-derived T cell lines from 20 HIV
      infected subjects is dominated by the response to a small number of peptide
      epitopes. Overlapping CTL epitopes restricted by multiple MHC Class I elements
      were identified in 3 relatively conserved regions of gp160 (amino acids 49-68,
      591-600 and 844-863). CTL from five of 20 subjects recognized three overlapping
      immunodominant epitopes in the 49-68 a.a. region restricted by A24, B38, and B55.
      CTL from four subjects recognized at least three distinct epitopes in a.a 591-600
      in the context of A24, B8, B14, and B27. CTL from seven subjects recognized
      epitopes within a.a. 844-863 restricted by A30, B7, B8 and B35.

PMID- 8877416
TI  - Phosphorous carbohydrates on chimeric CD22, CD44 and CD62L.
AB  - There are few examples of phosphorous carbohydrates described in higher animals.
      Here we have used recombinant molecules where the extracellular part of membrane
      receptors have been fused with the Fc part of human IgG (Rg-chimeras) to look at
      the prevalence of phosphorous carbohydrates. Also chimeras of a few hormones were
      used in this study. Thirteen Rg constructs were transfected into Cos cells and
      labelled with [32P]orthophosphate in phosphor deficient media. These Rg molecules
      were subsequently purified on protein A-Sepharose and submitted to SDS-PAGE and
      radiography. CD22Rg, CD62L-Rg and CD44Rg were all labelled very strongly with
      32P. From CD22Rg and CD62L-Rg the label could be easily removed by N-glycosidase
      F, but the 32P label on CD44Rg was resistant to N-glycosidase treatment. However,
      after treatment with O-glycosidase combined with sialidase, CD44Rg retained only
      a fraction of the 32P. Weakly phosphorylated Rg molecules were CD62E-Rg and
      CD7Rg. However, CD7Rg did not seem to loose the label, only shift position after
      N-glycosidase treatment and CD62E-Rg did neither shift position nor loose any 32P
      label after the N-glycosidase treatment. Negative chimeras were CD40Rg, CD33Rg,
      Lamp-1Rg, CD34Rg, ICAM-1Rg, TNF alpha Rg, CD19Rg and CD5Rg. The phosphate label
      of CD22Rg was completely removed after ALP treatment and in CD44Rg most of the
      label was removed. ALP is not supposed to cleave phosphodiesterbonds leading to
      the conclusion that the phosphor is likely present in the form of
      phosphomonoesters. This result is interesting as alkaline phosphatase (ALP) is
      common on the outer cellsurface of many cell types and might interact with
      phosphorous carbohydrates on membrane proteins. The membrane from of CD22 was
      also transfected into Cos cells and labelled with 32P in phosphate free media.
      Subsequently the cells were lysed and CD22 affinity purified and analysed by SDS
      PAGE and radiography. Under these conditions CD22 was shown to be 32P labelled,
      but only 20% of the label was removed by N-glycosidase F treatment. These results
      do not show that CD22, CD44 and CD62L are phosphorylated on carbohydrates under
      more physiological circumstances, but they do show that phosphorous carbohydrates
      might be more common in higher animals than what was been reported.

PMID- 8877417
TI  - HIV-1 epitopes exposed by hybrid hepatitis B core particles affect proliferation
      of peripheral blood mononuclear cells from HIV-1 positive donors.
AB  - Hepatitis B virus core protein (HBc) in particulate form is a potent immunogen
      for the design of vaccines with a broad T-cell reactivity. Hybrid HBc proteins
      with N-terminal insertions of human immunodeficiency virus (HIV-1) B- and T-cell
      epitopes from gp41 and p34 pol, respectively, were constructed HBc hybrids formed
      particles with HIV-1 epitopes exposed on the surface. The proliferative response
      of peripheral blood mononuclear cells (PBMC) from HIV-1 infected donors to the
      hybrids was studied in vitro and compared to that of synthetic peptides
      representing the same HIV-1 sequences. The epitope from p34 pol induced PBMC
      proliferation both when inserted into HBc and as a peptide. The epitope from
      gp41, when inserted into HBc, and to a lesser extent the relevant peptide caused
      a decreased reactivity. The inhibitory effect of the HBc hybrid carrying the gp41
      epitope was pronounced even in the HIV-1 infected donors with proliferative
      responses to HBc. The similarity between the mode of action of the peptides and
      hybrid HBcs implies either correct processing of the latter or T-cell recognition
      of HIV-1 epitopes in the intact hybrid HBc particles.

PMID- 8877418
TI  - Human thymocyte responsiveness to stem cell factor: synergy with interleukin-2
      for the generation of NK/LAK cytotoxicity.
AB  - Human recombinant stem cell factor (SCF) increases the viability and cell size of
      a subset of thymocytes in vitro, but does not independently induce phenotypic
      changes on thymocytes indicative of T cell differentiation. The SCF-responsive
      thymocytes have characteristics of large granular cells, that do not express T, B
      or NK cell-related antigens, and are primarily found in immature thymocyte
      subsets. These large granular thymocytes do not display cytotoxic activity.
      However, SCF acts synergistically with IL-2 in the generation of cytotoxic
      effector cells from thymocyte precursors. Synergy in cytotoxicity is observed to
      both NK-sensitive and NK-resistant targets. Studies of the SCF receptors on
      thymocytes show that receptors are expressed on mature 'bright' CD3+ cells,
      immature 'dim' CD3+ cells as well as CD3- cells. IL-2 increases the frequency of
      SCF receptor-positive cells in cultured thymocytes, which may explain its synergy
      with SCF in the generation of NK/LAK cytotoxicity. These data show that SCF
      enhances the functional development of thymic NK/LAK cells in vitro.

PMID- 8877419
TI  - Soybean agglutinin binds a 160-kDa rat macrophage membrane glycoprotein and
      enhances cell differentiation and activation.
AB  - Mature macrophages (M phi) differ from other rat leukocytes by their ability to
      bind soybean agglutinin (SBA). In this study we identify the SBA-binding
      structure on rat bone marrow-derived M phi (BMDM phi). Precipitation of iodinated
      membrane proteins from rat bone marrow cells (BMC) and BMDM phi with SBA revealed
      a major glycoprotein of Mr 160 kDa on BMDM phi but not on BMC. In addition minor
      bands migrating at 70 and 26 kDa were seen. Stimulation of BMDM phi with 100 nM
      SBA induced a decrease in surface density of Thy1.1 (MRC OX7) and His54 and an
      increase in the expression of MRC OX6 (RT1.B/I-A), MRC OX17 (RT1.D/I-E), MRC OX41
      (gp 110/120), MRC OX42 (CD11b/c), Macl (CD11b/CR3) and Mac2 (galectin-3/IgE
      binding protein) antigen. Expression of other M phi differentiation antigens
      recognized by mAb MRC OX43 (M phi, endothelial cells) and ED9 (M phi/CD14 like)
      were not significantly altered. BMDM phi derived from cultures with M phi colony
      stimulating factor (M-CSF) and SBA showed increased oxidative burst and
      phagocytic activity compared to cells cultured with M-CSF alone. Our data suggest
      that binding of a 160-kDa membrane glycoprotein on M phi by N-acetylgalactosamine
      specific lectins stimulates M phi differentiation and activation.

PMID- 8877420
TI  - Plasma levels of sTNFR p75 and IL-8 in patients with HIV-1 infection.
AB  - We determined the degree of activation of the TNF alpha system and the levels of
      IL-8 in HIV-1 infection. TNF alpha is one of the most potent agents for the
      induction of IL-8. TNF alpha may be cleared rapidly from the circulation, however
      soluble tumor necrosis factor receptor (sTNFR) p75 which is more stable may
      reflect the degree of activation of the TNF alpha system. We measured
      concentrations of sTNFR p75 and IL-8 with immunoassays in the plasma of 99 HIV-1
      infected patients at different stages of disease (Centers for Disease Control
      classification) and in 20 healthy control subjects. Plasma levels of sTNFR p75
      were elevated in most of the asymptomatic seropositive patients without CD4+ T
      cell depletion (Stage IIA) and in most of patients of all clinical groups
      compared with controls. However, in the majority of those patients plasma levels
      of IL-8 were not higher than those of controls. Our results suggest that sTNFR
      p75 levels but not IL-8 levels in circulating blood are high in the course of HIV
      1 infection.

PMID- 8877421
TI  - Cardiac energy metabolism at several stages of adriamycin-induced heart failure
      in rats.
AB  - To evaluate the changes in myocardial energy metabolism in the progressively
      failing myocardium, we measured myocardial level of adenosine triphosphate (ATP)
      using high-performance liquid chromatography (HPLC), and levels of lactate,
      alanine and free carnitine using 1H-nuclear magnetic resonance (NMR) spectroscopy
      in rats injected with adriamycin. The drug was injected intraperitoneally 2.5
      mg/kg 6 times over a period of 2 weeks. Measurements were obtained 1 day (1 d), 3
      weeks (3 w) and 6 weeks (6 w) after the last injection. No deaths were observed
      until the end of the 3rd week. The cumulative mortality rate 6 weeks after the
      last injection was 48%. ATP and free carnitine levels were not significantly
      changed at 1 d, while myocardial lactate was increased by 33% from the control
      values (P < 0.05). Lactate levels were reduced significantly, but not
      progressively, at 3 w (31% of control values) and at 6 w (69% of control values).
      Similar changes were observed in alanine levels. Free carnitine levels were
      progressively decreased at 3 w (74% of control values) and at 6 w (57% of control
      values). Changes in ATP levels paralleled those of free carnitine. Data suggest
      that a decrease in the myocardial level of free carnitine may be involved in
      progression of the heart failure induced by adriamycin in rats.

PMID- 8877422
TI  - No evidence for ischemic preconditioning during repeated vessel occlusion in
      coronary angioplasty.
AB  - Coronary angioplasty has been the favoured model in studying ischemic
      preconditioning in humans, but results have remained controversial, possibly due
      to some artefacts related to coronary balloon angioplasty as an ischemia model.
      We examined this issue by monitoring the sequential metabolic, functional and
      neurohumoral changes during repeated vessel occlusion in coronary angioplasty
      performed in patients with chronic angina pectoris. Two groups of patients
      undergoing two successive balloon inflations of approximately 2 min duration were
      studied. These balloon inflations were preceded by a short inflation performed
      immediately after introduction of the balloon into the stenosis. The aim of this
      primary inflation was to establish adequate coronary blood flow with the deflated
      balloon in the stenosis and to guarantee that the subsequent two balloon
      inflations were truly comparable in time. Group I consisted of 23 patients, in
      whom the changes in the degree of angina, pulmonary capillary wedge pressure
      (PCWP), atrial natriuretic peptide (ANP) and circulating catecholamines during
      the procedure were studied. The sequential changes in myocardial metabolism were
      monitored in group II of nine patients by determining the lactate extraction
      ratios and femoroarterial coronary sinus (Fa-CS) differences in pH and pCO2
      before and after each balloon inflation. In group I, PCWP and total
      catecholamines increased similarly during both balloon inflations, but ANP
      remained unchanged. In group II patients the lactate extraction ratios turned
      negative, the Fa-CS pH-differences increased and the pCO2-differences decreased
      during vessel occlusions, the changes being somewhat more prominent during the
      second balloon inflation. To study adaptation to ischemia, the group I patients
      were divided into two subgroups with and without signs of ischemic dysfunction
      during balloon inflations (PCWP increase > 5 mmHg and < 5 mmHg, respectively),
      and the group II patients were divided into two subgroups with and without
      metabolic ischemia (lactate-producers and non-producers). The ANP levels were
      constantly higher in the patients demonstrating ischemic dysfunction during
      balloon inflations, but catecholamine levels increased only after the second
      balloon inflation. The anginal pain experienced by the patients and the signs of
      metabolic ischemia were identical during both balloon inflations. We conclude
      that acute ischemic preconditioning does not occur in patients with repeated
      vessel occlusions of approximately 2 min duration. The patients without ischemia
      during the procedure had more critical stenoses and pre-existing collaterals.
      However, other protective mechanisms, such as chronic adaptation at the cellular
      level or recruitment of new collaterals, cannot be excluded.

PMID- 8877423
TI  - Myocardial indium-111 antimyosin uptake after uncomplicated coronary artery
      bypass surgery.
AB  - The prevalence of myocardial damage after coronary artery bypass grafting is
      related to the criteria of its evaluation. Indium-111 monoclonal antimyosin
      antibody scintigraphy has been shown to be highly sensitive and specific for even
      small areas of myocardial necrosis or injury like those of myocarditis or
      transplant rejection. Our purpose was to evaluate, by using this method,
      myocardial damage after uncomplicated coronary artery bypass grafting. Uptake of
      this radio tracer was evaluated after coronary artery bypass grafting in 14
      informed and consenting consecutive patients without previous myocardial
      infarction, with no post-surgical complications and a favorable postoperative
      course, following coronary artery bypass grafting for stable angina pectoris.
      Monoclonal antimyosin antibody indium-111 74 MBq (Myoscint Centocor) was injected
      on the third postoperative day; planar images in the anterior, left anterior
      oblique 45 degrees and 70 degrees projections were obtained 24 and 48 h later and
      analyzed for myocardial uptake. Indium-111 antimyosin uptake was present in 10
      out of 14 patients (71.4%); it was diffuse in 6 and localized in 4. The ratio of
      the maximal counts in the myocardium to the counts in the adjacent lung
      background was measured and found elevated: 1.94 +/- 0.23, higher than the normal
      values reported in the literature. Indium-111 antimyosin uptake was clear in a
      group of patients after uncomplicated coronary artery bypass grafting. No
      correlation was observed between indium-111 antimyosin uptake or heart to lung
      ratio and creatine kinase, creatine kinase isoenzyme MB, glutamic oxalacetic
      transferase levels, duration of cardiopulmonary bypass or aortic cross-clamp
      time, while elevated serum beta myosin heavy chain fragments (IRMA Pasteur) were
      observed (1378 +/- 238 microU/l). This study suggests that some degree of
      myocardial damage, though silent, is common after coronary artery bypass
      grafting.

PMID- 8877425
TI  - 'Abnormal' diastolic Doppler patterns in patients over age 65 with severe left
      ventricular systolic dysfunction.
AB  - OBJECTIVE: The purpose of this study was to determine whether Doppler diastolic
      filling patterns of the left ventricle are altered in patients over age 65 with
      poor left ventricular function, compared to patients with normal left ventricular
      systolic function. BACKGROUND: In elderly, healthy subjects, the mitral valve
      Doppler inflow pattern exhibits an increase in atrial contribution to left
      ventricular filling. Myocardial disease, which results in stiffness, may also
      cause an increase in A wave velocity. METHODS: Twenty-seven patients over age 65,
      with left ventricular systolic dysfunction, were age and sex-matched with 19
      patients with normal left ventricular systolic function. Patients with
      significant mitral or aortic valvular disease were excluded. Maximal early inflow
      velocity, maximal atrial inflow velocity, heart rate, acceleration time and
      deceleration time were calculated. RESULTS: Comparing the group with normal left
      ventricular systolic function, the group with decreased left ventricular systolic
      function had pseudonormalization of the maximal early flow/atrial flow velocity
      ratio (1.7 +/- 1.3 vs. 0.9 +/- 0.3; P = 0.003), E wave velocity was similar (82
      +/- 28 vs. 70 +/- 24 cm/s; P = n.s.), and A wave velocity was diminished (66 +/-
      30 vs. 84 +/- 20 cm/s; P = 0.02). The acceleration time was similar for the
      groups (53 +/- 17 vs. 46 +/- 21 ms), but the deceleration time was shorter in
      patients with left ventricular systolic dysfunction (122 +/- 33 vs. 192 +/- 80
      ms; P < 0.001). CONCLUSION: Such differences may relate to increased left atrial
      pressure, increased left ventricular diastolic pressure and/or decreased atrial
      systolic function. These findings are important when interpreting left
      ventricular filling indices by Doppler echocardiography in elderly patients.

PMID- 8877424
TI  - Comparison between Japan and North America in the post-hospital course after
      recovery from an acute coronary event.
AB  - We compared the post-hospital prognosis after an acute coronary event (acute
      myocardial infarction and unstable angina) in 106 patients in Japan vs. 789
      patients in North America who were prospectively enrolled in the Multicenter
      Study of Myocardial Ischemia and were followed-up for an average of 26 months per
      patients. Risk factors more frequent in Japan were older age, males and smoking
      at enrollment, but the rest of many risk factors were similar. After adjusting
      for differences in clinical and medication variables, Cox analyses indicated
      patients in North America had a significantly greater risk of experiencing a
      primary end-point (cardiac death, non-fatal myocardial infarction or unstable
      angina) than patients in Japan (hazard ratio [North America:Japan] = 3.1, P =
      0.003). There was a non-significant trend in the restricted end-points (cardiac
      death or non-fatal myocardial infarction) with North America having more frequent
      events than Japan (hazard ratio = 2.2, P = 0.12). The long-term outcome after
      recovery from an acute coronary event is more favorable in Japan than in North
      America, mostly due to a reduction in subsequent hospitalization for unstable
      angina. The reason for these findings cannot be explained by differences in the
      measured risk factors or medications.

PMID- 8877426
TI  - Prostaglandin E1 (PGE1) reduces cardiac-derived TXA2 release in ischaemic arrest
      in isolated working rat heart.
AB  - To determine whether PGE1 plays a beneficial role in crystalloid cardioplegia in
      the isolated working rat heart, twenty isolated rat hearts were studied. The
      hearts were subjected to 90 min cardioplegic arrest under hypothermia (25 degrees
      C) and 30 min reperfusion. Prior to ischaemic arrest, the amount of TXA2 in
      coronary effluent, left ventricular developed pressure (LVDP), left ventricular
      end diastolic pressure (LVEDP), coronary flow (CF), aortic flow (AF) and cardiac
      output (CO) did not differ between the control and PGE1 treated rats (28 nmol/l).
      However, at 30 min reperfusion, the recovery of LVDP, LVEDP, CF, AF, CO and SV in
      hearts from PGE1 treated rats was more than in control hearts. TXA2 levels from
      coronary effluent were increased during reperfusion in control rats. On the other
      hand, PGE1 (28 nmol/l) inhibited the release of TXA2 at reperfusion. The present
      studies confirm that the cardiac-derived TXA2 are increased after
      ischaemia/reperfusion. Infusion of cardioplegia solution containing PGE1 results
      in the inhibition of release of cardiac-derived TXA2 and in a better preservation
      of cardiac function after ischaemic arrest.

PMID- 8877427
TI  - Prominent atrial wave and diastasis deflection in the radionuclide diastolic
      volume curve during exercise--sensitive marker for coronary artery disease.
AB  - It is well-known that many patients with coronary artery disease have reduced
      left ventricular diastolic distensibility with normal systolic function. However,
      researchers have to data focused on the diastolic rapid filling phase of the
      radionuclide volume curve in ischemic patients, paying less attention to the
      ensuing left ventricular filling associated with passive filling ('diastasis')
      and atrial contraction ('A' wave). We analyzed the radionuclide volume curves of
      27 consecutive patients suspected ischemic heart disease, who manifested normal
      systolic function at rest and during exercise, as assessed by multigated
      equilibrium technetium-99m radionuclide cineangiography. For all patients, the
      amplitude of the maximal 'A' deflection relative to the peak of the diastolic
      curve (presented as percentage units) was calculated manually from the
      radionuclide left ventricular volume curves obtained at rest and during exercise.
      Twenty patients (Group I) had transient perfusion defects on thallium
      scintigraphy (treadmill), and 7 (Group II) did not. Patients in Group I
      manifested prominent 'A'-deflections during exercise, with a rise of 120 +/- 43%
      (mean +/- S.D.) from rest to exercise, whereas the patients in Group 11 had only
      34 +/- 11% (mean +/- S.D.) rise in 'A' wave amplitude during exercise (P =
      0.0001). We conclude that the appearance of a prominent 'A' deflection in the
      radionuclide left ventricular volume curve during exercise might be a sensitive
      marker of myocardial ischemia.

PMID- 8877428
TI  - The long term prognosis in patients following thrombolysis for acute myocardial
      infarction: a view from a community hospital.
AB  - Thrombolysis in patients with acute myocardial infarction has been established to
      improve hospital survival. Less information is available about the long term
      evolution of unselected patients seen in community hospitals. Consequently,
      consecutive patients treated with thrombolysis for acute myocardial infarction
      and surviving until hospital discharge (n = 129) were followed for an average of
      22 months. Mortality, recurrent ischemic events, coronary angiography and re
      vascularizations were recorded for all patients. Two-year total and
      cardiovascular survival rates of 95 and 98% respectively were obtained with a
      conservative approach to early re-vascularization (n = 17, 13%). A history of
      prior myocardial infarction and early recurrent myocardial ischemia were
      significant predictors of increased cardiac events, while thallium stress testing
      provided no incremental value. Angiography and re-vascularizations were more
      frequently performed in younger patients (under 65 years old), anterior vs.
      inferior infarction and those with early residual ischemia. Women received less
      aggressive investigation and therapy then men and this may represent a gender
      bias, unmeasured residual confounding or the play of chance in a small sample
      size. Further studies are needed to confirm or refute these findings.

PMID- 8877429
TI  - Dilatation of sinus of Valsalva with displacement and compression of the left
      coronary artery causing sudden death.
AB  - A 69-year-old male patient is described who presented with angina and congestive
      heart failure 12 years after his aortic valve had been replaced by a
      bioprosthesis for aortic stenosis. The aortogram showed massive dilatation of the
      aortic root. Coronary angiography demonstrated a displaced and narrowed left main
      and circumflex coronary artery. The patient died suddenly before his scheduled
      elective operation. At autopsy the left main and circumflex coronary artery were
      patent but severely compressed by extensive dilatation of the aortic root,
      predominantly of the left sinus of Valsalva. His sudden death was most likely due
      to external constriction of the left coronary artery with subsequent ischemia and
      ventricular fibrillation.

PMID- 8877430
TI  - Aortic dissection during directional coronary atherectomy.
AB  - Directional coronary atherectomy has been applied to aorto-ostial lesions with
      higher success and lower complication rates than conventional balloon
      angioplasty. Aortic injuries have been reported with this technique, most
      resulting from the tip of the catheter. In this report, an aortic dissection
      caused by the shaft of the directional coronary atherectomy catheter is
      described.

PMID- 8877431
TI  - An unusual association: sick sinus syndrome and congenital cataract in a 6-month
      old girl.

PMID- 8877432
TI  - What are the key advantages and disadvantages of urodele species compared to
      anurans as a model system for experimental analysis of early development?

PMID- 8877433
TI  - Urodele limb and tail regeneration in early biological thought: an essay on
      scientific controversy and social change.
AB  - Lazzaro Spallanzani (1729-1799) announced his discoveries of salamander tail and
      limb regeneration to Charles Bonnet (1729-1793) in the 1760's. The phenomenon
      soon became embroiled with the ongoing epigenesis/preformation controversy over
      the fundamental nature of generation. The concept of animal regeneration as a
      process linked to reproduction had emerged in 1740 with Abraham Trembley's (1710
      1783) demonstration that a bisected hydra gives rise to two new, completely
      formed individuals. The discovery of urodele appendage regeneration revealed for
      the first time that a quadruped could regenerate and restore complex form, lizard
      tail regenerates having been recognized as only substitute structures. Moreover,
      regeneration of a quadruped appendage became problematic because it was not
      supposed to be possible and because it conflicted with prevailing opinion about
      the nature of higher organisms. Why animal regeneration in general engendered
      conflict transcends biological concerns and touches on personal philosophical
      commitments. Preformation had been adopted into orthodox theology as a validation
      of predestination and of the hierarchical structuring of man's relationships to
      nature and within society. Epigenetic interpretations of regeneration represented
      challenges to certain aspects of the extant social and political fabric in their
      extrapolation to ideas of what constituted natural order. Urodele regeneration as
      an integral part of the epigenesis/preformation debate therefore constituted a
      formative component of eighteenth century thought in a period of social and
      intellectual revolution.

PMID- 8877434
TI  - How did urodele embryos come into prominence as a model system?
AB  - Experimental studies on amphibian embryos started mainly in Germany during the
      last two decades of the 19th century. At first, urodele amphibians were used much
      less frequently than anurans. At that time, embryological studies on urodeles
      were mostly descriptive and comparative. In Germany, Spemann (1900)--immediately
      followed by Harrison in the United States--began extensive studies on the newt
      egg and early embryo. Those studies finally led to the prominence of urodele
      embryos in general experimental embryology during the period 1920-1950.
      Milestones of that era are described and the main researchers are indicated.

PMID- 8877435
TI  - Unusual features of the urodele genome: do they have a role in evolution and
      development?
AB  - Urodeles are amongst the organisms with the highest C-values. They provide a
      useful system for studies of genome organization at both the chromosomal and the
      molecular level. In this contribution we discuss the general features of "excess"
      DNA in urodeles and emphasize that the urodele genome is in a state of
      plasticity. That fluidity is due to various molecular mechanisms which are
      involved in its continuous turnover. The implications of this fluid, "excess DNA"
      for evolution and/or development are considered.

PMID- 8877436
TI  - What role might lampbrush chromosomes play in maternal gene expression?
AB  - The biological significance of lampbrush chromosomes from urodelan amphibians is
      far from being elucidated. Their particularly well developed lateral loops are
      the site of intense transcriptional activity, which can be visualized in electron
      microscopy using the Miller spreading procedure. All transcription units
      functioning in lampbrush loops synthesize RNA at a maximum rate. In situ
      hybridization has provided evidence for transcription of both unique coding
      sequences and highly repetitive sequences. The role of lampbrush transcripts in
      the production of maternal information remains unclear. RNAs transcribed from
      unique coding sequences are exported to the cytoplasm; there, they contribute
      either to maintaining the required level of maternal messenger RNA in a basal
      state during late oogenesis, or to increasing the store of these maternal RNAs
      throughout oocyte growth, i.e., until stage VI. For repetitive sequences, their
      intense transcription appears to be non-productive, in that RNAs are not
      translatable and might be useless products of readthrough transcription. The non
      productive transcription of repetitive sequences, the expression of which is
      directly related to hyperdevelopment of lateral loops, raises the issue of the
      role of lampbrush chromosome transcription.

PMID- 8877437
TI  - Primordial germ cell development: is the urodele pattern closer to mammals than
      to anurans?
AB  - All animals can be classified into three types depending on their modes of germ
      cell formation; epigenetic, intermediate and preformistic. In urodeles, which
      show the intermediate mode, primordial germ cells (PGCs) are morphologically
      recognized at first in early tailbud embryos. The PGCs, which are located within
      the lateral plate mesoderm, are induced as part of the regional induction of the
      mesoderm by the vegetal yolk endoderm. No cytologically distinctive, germ cell
      specific germ plasma can be detected during early development of urodeles.
      'Nuage' materials, which are specific to germ line cells in almost all animals,
      do, however, appear in the cytoplasm of the urodele PGCs during later
      embryogenesis. In contrast, PGCs in anurans are preformistically established
      under the influence of germ plasma. Because all germ cells, once established,
      show virtually identical behavior, regardless of whether different modes of germ
      cell formation are employed, the basic mechanism of germ cell formation and
      differentiation in all animals could be similar at the molecular levels. Although
      the molecules involved in germ cell formation in amphibians have not been
      identified, many aspects of germ plasm formation in anurans are similar to
      Drosophila, in which three classes of genes involved in germ cell formation have
      been identified: Class I genes are necessary for pattern specification during
      germ cell formation, Class II for the assembly of germ plasm components, and
      Class III for germ cell segregation. Assuming that germ cell formation in all
      animals requires the expression of all such genes, the three modes of germ cell
      formation mentioned above could be explained in terms of spatio-temporal
      expression of genes which are similar to those that have been identified in
      Drosophila. A tentative model of gene regulation for the three different modes of
      germ cell formation has been proposed in terms of temporal expression of these
      three classes of genes.

PMID- 8877438
TI  - Surface contraction and expansion waves correlated with differentiation in
      axolotl embryos. II. In contrast to urodeles, the anuran Xenopus laevis does not
      show furrowing surface contraction waves.
AB  - We have observed a number of contraction waves traversing the axolotl (Ambystoma
      mexicanum) embryo (a urodelan amphibian) from the midblastula transition up to at
      least neural tube closure, and wished to learn if similar "differentiation waves"
      appear on the popular laboratory anuran amphibian, the South African clawed toad,
      Xenopus laevis. Time lapse video microscopy showed that no contraction waves are
      visible on the surface of Xenopus from gastrulation through neurulation. It is
      possible that cell intercalations in the double-layered ectoderm of the Xenopus
      embryo are homologous to the surface waves in the single layered ectoderm of the
      axolotl embryo. In any case, a simple, universal correspondence between surface
      waves and induction phenomena and differentiation does not exist.

PMID- 8877439
TI  - What mechanisms control neoteny and regulate induced metamorphosis in urodeles?
AB  - The Mexican axolotl, like a number of other urodele species, is an obligatory
      neotene, completing its full life cycle without metamorphosis. Metamorphosis can
      be induced with thyroid hormone, thyroid stimulating hormone, or stimulation of
      hypothalamic neurons. Thus, neoteny represents a deviation from the standard
      course of amphibian ontogeny, affecting the thyroid axis at one or more levels.
      Analysis of the thyroid axis at strategic ontogenic stages and after completed
      neotenic development suggests that there are a number of deviations, and that the
      deviations may be temporal and/or quantitative in nature. A surge of thyroxine
      secretion occurs early in larval life but does not lead to metamorphosis,
      apparently because the enzyme which deiodinates thyroxine to the active form,
      triiodothyronine, is not yet present. Later in ontogeny, activity in the thyroid
      axis is low. Hormone treatment can reactivate the thyroid axis at all levels, but
      some singularities remain. Inhibition at central nervous or peripheral levels may
      be involved in axolotl neoteny.

PMID- 8877441
TI  - What insights into vertebrate pigmentation has the axolotl model system provided?
AB  - Amphibians have been judiciously exploited by developmental biologists for many
      years for studying basic developmental mechanisms in vertebrates. In this review,
      the contributions that have been made by urodeles, in particular the axolotl
      (Ambystoma mexicanum), to the study of pigment cell biology are elaborated.
      Pigment cell differentiation is described, and the wild-type pigment phenotype is
      contrasted to pigment mutants such as albino, axanthic, melanoid, and white.
      Methods used for studying pigmentation, including recently developed molecular
      biological tools, are included to illustrate the significance of the axolotl as a
      model system for studying vertebrate pigmentation.

PMID- 8877440
TI  - What mechanisms drive cell migration and cell interactions in Pleurodeles?
AB  - Embryogenesis implies a strict control of cell interaction and cell migration.
      The spatial and temporal regulation of morphogenetic movements occurring during
      gastrulation is directly dependent on the early cell interactions that take place
      in the blastula. The newt Pleurodeles waltl is a favorable model for the study of
      these early morphogenetic events. The combination of orthotopic grafting and
      fluorescent lineage tracers has led to precise early gastrula mesoderm fate maps.
      It is now clear that there are no sharp boundaries between germ layers at the
      onset of gastrulation but rather diffuse transition zones. The coordination of
      cell movements during gastrulation is closely related to the establishment of
      dorsoventral polarity. Ventralization by U.V. irradiation or dorsalization by
      lithium treatment modifies the capacity for autonomous migration on the
      fibronectin coated substratum of marginal zone cells accordingly. It is now
      firmly established that mesodermal cells need to adhere to a fibrillar
      extracellular matrix (ECM) to undergo migration during gastrulation.
      Extracellular fibrils contain laminin and fibronectin (FN). Interaction of cells
      with ECM involves receptors of the beta 1 integrin family. A Pleurodeles homolog
      of the alpha v integrin subunit has been recently identified. Protein alpha v
      expression is restricted to the surface of mesodermal cells during gastrulation.
      Integrin-mediated interactions of cells with FN are essential for ECM assembly
      and mesodermal cell migration. Intracellular injection of antibodies to the
      cytoplasmic domain of beta 1 into early cleavage embryos causes inhibition of FN
      fibril formation. Intrablastocoelic injections of several probes including
      antibodies to FN or integrin alpha 5 beta 1, competitive peptides to the major
      cell binding site of FN or the antiadhesive protein tenascin all block mesodermal
      cell migration. This results in a complete arrest of gastrulation indicating that
      mesodermal cell migration is a major driving force in urodele gastrulation. It is
      now possible to approach the role of fibroblast growth factor (FGF) during cell
      interactions taking place in urodele embryos. Four different FGF receptors (FGFR)
      have been cloned in Pleurodeles. Each of them has a unique mRNA expression
      pattern. FGFR-1, FGFR-3, and the variant of FGFR-2 containing the IIIb exon are
      maternally expressed and might be involved in mesodermal induction. During
      gastrulation, FGFR-3 and FGFR-4 have a restricted pattern of expression, whereas
      FGFR-1 mRNA is nearly uniformly distributed. Splicing variants FGFR-2IIIb and
      FGFR-2IIIc have exclusive expression patterns during neurulation. IIIb is
      expressed in epidermis and IIIc in neural tissue, suggesting a function in the
      differentiation of ectodermal derivatives.

PMID- 8877442
TI  - What insights into the phenomena of cell fate determination and cell migration
      has the study of the urodele neural crest provided?
AB  - In this review we ask whether studies on the development of the urodele neural
      crest (NC) have provided special insights into the fate and migration of these
      cells when compared to other amphibian embryos or those of higher vertebrates. We
      recognize that during the first half of this century and even before, urodele
      embryos were the favorite objects of experimental embryology for studying the
      development of mesenchymal derivatives and their participation, together with
      mesodermal mesenchyme, in the development of the neuro- and viscerocranium.
      Furthermore, the NC was discovered to be the source of cranial sensory and spinal
      ganglia, and the influence of the somites on the localization of the latter was
      clearly pointed out. In addition, pioneering studies were devoted to the NC
      derived pigment cells. Investigations in this field concentrated on their
      migration in the embryo and in vitro, and on the mechanisms underlying larval
      pigment pattern formation. It is mainly in these three areas that the urodele
      embryo has served as a tool for gaining major results and defining the concepts
      of classical embryology. Even today, when the interest has shifted towards the
      molecular biology in Xenopus, chicks and mice, the urodele embryo with its large
      cells, convenient for injections, is a potential model for future lineage studies
      and knockout experiments. And furthermore, as important concepts of vertebrate
      development are defined in the urodele, future studies in these embryos may link
      the disciplines of development and evolution.

PMID- 8877443
TI  - Morphogenesis of the axolotl pronephric duct: a model system for the study of
      cell migration in vivo.
AB  - Pronephric duct (PND) morphogenesis is a critical early event in the development
      of the vertebrate excretory system. This structure is the exit channel for both
      pronephric and mesonephric filtrate, forms the ureteric bud of the metanephros
      and gives rise to the ductus deferens of the testis. In addition, the PND and
      ureteric bud epithelia induce terminal differentiation of the mesonephric and
      metanephric mesenchyme, respectively. Elongation of the PND in all vertebrates
      involves active cell migration of the primordium. In urodele embryos--unlike in
      some anuran, avian and mammalian embryos--elongation of the PND occurs solely by
      cell migration. In the axolotl embryo, the PND primordium segregates as an ovoid
      tissue mass from the anterodorsal flank mesoderm directly beneath somites 3-7.
      The primordium then extends caudally along the ventral border of the developing
      somites until it reaches the cloaca. The ease with which these embryos can be
      manipulated microsurgically makes the PND system ideal for the study of the
      mechanisms controlling cell migration in vivo. This review summarizes the
      progress that has been made in characterizing the environmental cues and the cell
      surface recognition systems that drive this tightly regulated migration event.

PMID- 8877444
TI  - Activin treated urodele ectoderm: a model experimental system for cardiogenesis.
AB  - The tissue interactions which comprise the inductive phenomena associated with
      urodele heart morphogenesis are relatively well understood. In order to take full
      advantage of the experimental potential of this system formulation of an in vitro
      tissue culture system would be very helpful. Herein are described conditions for
      culturing Cynops pyrrhogaster early gastrula ectoderm tissue in the presence of
      the peptide growth factor activin. Two-week old explant cultures frequently
      displayed beating heart-like rudiments within. The beating frequency was measured
      and the extent to which cytodifferentiation mimicked normal heart differentiation
      assessed. Both measurements provided optimistic assessments which should
      encourage further exploitation of this model system.

PMID- 8877445
TI  - Heart development and regeneration in urodeles.
AB  - Classical fate mapping and transplantation studies have yielded a rich
      embryological understanding of heart development in urodeles. Recent advances in
      understanding the molecular nature of many early developmental events can be
      applied to urodele heart development. In this review we examine urodele heart
      development from both morphological and molecular viewpoints. We focus primarily
      on cardiac induction, early cardiogenesis, and heart regeneration.

PMID- 8877446
TI  - Pattern formation in the urodele mechanoreceptive lateral line: what features can
      be exploited for the study of development and evolution?
AB  - The lateral line is a specialized system of mechano- and electrosensory organs
      found in anamniotes. This system develops from ectodermal placodes, which migrate
      extensively along specific routes and deposit sensory organ anlagen at regular
      intervals, making it ideal for examining several important aspects of pattern
      formation. Urodele embryos are excellent model organisms for studies of pattern
      formation in the lateral-line system. The results of such studies are also
      important for understanding the evolutionary control of changes in pattern. The
      developmental mechanisms which control pattern formation in the urodele lateral
      line are reviewed, and some of the broader evolutionary implications of these
      mechanisms are discussed.

PMID- 8877447
TI  - Developmental neurobiology of the anterior areas in amphibians: urodele
      perspectives.
AB  - Because of its evolutionary grade and its relative simplicity, the Urodele brain
      provides an excellent archetype for the study of forebrain development. Early
      experiments on Primary Induction took advantage of the Urodele's manipulatability
      and ease of use, but due to the fact that its ectoderm was very readily
      neuralized Anurans (especially Xenopus) became the vertebrate of choice for early
      developmental neurobiology. Recent advances in the molecular biology of
      neuralization in Xenopus may rejuvenate Urodele use in solving the complicated
      sequence of events during this process of neural induction and to ascertain if
      separate or a combination of events (de fault and inductive) are involved. In the
      future, the combined use of Urodeles and Anurans will provide much information
      with regard to the evolutionary conservation of the mechanisms of regional
      specification, gene expression events, neurulation, neuroblast migration, and
      axonogenesis during the development of the nervous system. The present review
      provides some recent examples of this approach of using Urodeles and Anurans in a
      combinatorial fashion to decipher specific aspects of developmental neurobiology.

PMID- 8877448
TI  - What mechanisms drive neural induction and neural determination in urodeles?
AB  - In our laboratory we use Urodeles (Pleurodeles waltl) and Anurans (Xenopus
      laevis) to perform comparative studies on neural determination. Urodeles are a
      good embryological system to study early events in ontogenesis since they present
      several advantages: slow development, external localization of chordamesoderm at
      the beginning of gastrulation, large size of cells, diploid genome, etc. I have
      focused this overview-report on the main findings on Pleurodeles neurogenesis.
      The determination of the two neural lineages (neuronal and astroglial) appears
      during gastrulation as a consequence of (a) permissive event(s) activated through
      a Ca(++)-dependent transducing pathway. This signaling-pathway involves L-type
      Ca++ channels. The activation of this Ca++ transduction route is sufficient to
      activate both neuronal and glial structural specific genes, via direct activation
      of "immediate early genes". The specification of neuronal functional
      differentiation depends on additional factors of chordamesoderm origin acting
      during gastrulation and later on. At the early neurula stage, in the neural
      plate, 20% of progenitor cells present a neuronal fate, 80% are at least
      bipotential and generate mixed clones (neurons and astrogliocytes). The issue of
      the state of "commitment" of the precursor cells (competent ectoderm) and the
      identification of specifying molecules (from Spemann organizer) are underway in
      Pleurodeles and Xenopus.

PMID- 8877449
TI  - Lens induction in axolotls: comparison with inductive signaling mechanisms in
      Xenopus laevis.
AB  - Amphibian lens induction is an embryonic process whose broad outlines are
      conserved between anurans and urodeles; however, it has been argued that some
      aspects of this process differ significantly between even closely related
      species. Classical embryologists concluded that in some species direct contact
      between the optic vesicle and ectoderm was both necessary and sufficient to
      induce the ectoderm to form a lens, while in other species tissues other than the
      optic vesicle induce lens formation. Recent studies of lens induction in Xenopus
      have argued that lens induction may be more conserved evolutionarily than was
      previously thought and that the different conclusions reached in the classical
      literature may be due more to experimental methodology than to actual differences
      in the process of lens induction. We have tested this hypothesis by examining the
      timing of lens induction in the axolotl and the ability of various tissues to
      induce lenses in explant cultures. We find that, despite the evolutionary
      divergence between Xenopus and Ambystoma, the mechanism of lens specification is
      substantially similar in the two species. These results support the hypothesis
      that the mechanism of lens induction is evolutionarily conserved among
      amphibians.

PMID- 8877450
TI  - How does the urodele ear develop?
AB  - An overview is provided of the structural and molecular events causing the
      transformation of undifferentiated epidermal cells together with the underlying
      mesenchyme to become the complex, three-dimensional ear. While tremendous
      progress has been achieved in a few model systems, enough is not yet known about
      the comparative embryology of ear development to provide causal explanations of
      the adult structural differences among species. It is hoped that the changes in
      selector and/or structural genes, as well as changes in the spatiotemporal
      induction of structural gene activation, and possible changes in the interaction
      between the various embryonic sources which contribute to the ear, will soon be
      understood. The most promising new avenue for research appears to be studies
      which combine classical transplantation tissue experiments with modern gene
      expression analyses and modern in vitro assays of the role of putative morphogens
      or trophic factors. It is emphasized that it is not understood what is missing in
      the developmental program of those salamanders which have lost a basilar papilla.
      Direct comparison of gene expression patterns and xenoplastic transplantations in
      salamanders of comparable stages which either do or do not develop this organ
      should help to clarify the molecular events that have led to this major
      evolutionary novel feature of the vertebrate ear.

PMID- 8877451
TI  - A conceptual framework for analyzing axial patterning in regenerating urodele
      limbs.
AB  - This review describes what we have learned about mechanisms of patterning in
      regenerating urodele limbs. Experimental evidence for three concepts is
      presented. First, the regeneration blastema is a self-organizing system based on
      positional memories inherited from parent limb cells. Second, the autonomous
      patterning mechanism involves local cell interactions that determine patterns of
      Hox gene activation. The effector molecules for positional identity reside in or
      on the cell surface, and can be altered by retinoic acid. Third, proximodistal
      patterning of the blastema is linked to blastemal growth, which in turn is
      dependent on a signal from the apical epidermal cap and on the non-uniformity of
      positional identity in the transverse axes. Lastly, the question of the degrees
      of similarity between the mechanisms of urodele limb regeneration, urodele limb
      embryogenesis, and the embryogenesis of other tetrapod limbs is discussed.

PMID- 8877452
TI  - The cellular basis of limb regeneration in urodeles.
AB  - Formation of a regeneration blastema on the amputated urodele limb involves
      changes in the gene activity of differentiated cells resulting in their
      histological dedifferentiation and their return to a proliferative state. This
      review summarizes studies in limb regeneration and in the related fields of
      tissue repair and limb development that provide new insights into regulatory
      mechanisms of likely importance in establishing the blastema. Factors required
      for epithelialization of the wound are briefly described, followed by what is
      known regarding the biochemistry of extracellular matrix remodeling in the
      regenerating limb. Cellular "dedifferentiation" is discussed, emphasizing
      variations in the process among major cell types that give rise to the blastema:
      fibroblasts, cells of skeletal tissue, muscle cells, Schwann cells, and vascular
      endothelial cells. Attention is drawn to evidence that cells of connective tissue
      have a special role in establishing the prepattern of the new limb in the early
      phase of blastema formation and that angiogenesis may be controlled differently
      during epimorphic regeneration than in the process of wound repair. Several
      possible sources of the mitogens which stimulate cell cycle re-entry during
      dedifferentiation are described, as well as evidence suggesting the importance in
      limb regeneration of one such class of mitogens, the fibroblast growth factors.
      The trophic effect of nerves required for cells of dedifferentiating tissues to
      progress through the cell cycle is summarized briefly, along with recent work
      suggesting how this neural influence is exerted. Finally, the critical role of
      the wound epithelium in the cellular events forming the blastema and factors that
      may mediate the epithelial effect are discussed.

PMID- 8877453
TI  - Molecular mechanisms in the control of limb regeneration: the role of homeobox
      genes.
AB  - Axolotls are unique among vertebrates in their ability to regenerate lost
      appendages as adults. They provide the opportunity to study the mechanism of
      regeneration in vertebrates and are an inspiration to pursue the goal of
      appendage regeneration in humans. In this article, we review data on the role of
      homeobox-containing genes in the regulation of limb regeneration. As a group,
      these genes are important in pattern formation in the primary body axis,
      developing limbs and regenerating limbs. To date, a total of 22 homeobox genes
      have been identified as being expressed in regenerating limbs. Nearly all of
      these are also expressed during limb regeneration, further supporting the view
      that limb development and regeneration involve similar regulatory mechanisms. Our
      recent results on the expression of HoxA genes demonstrate that once a blastema
      has formed, subsequent outgrowth and pattern formation are similar to those of
      limb development. In contrast to developing limbs, reexpression of the HoxA genes
      in regeneration occurs by a non-colinear mechanism that likely is related to the
      necessity of mature limb cells to undergo dedifferentiation in order to give rise
      to the blastema. These studies also indicate that the pattern is respecified by a
      distal-first mechanism during regeneration in contrast to the apparent proximal
      to-distal sequence observed in developing limbs. Expression of the HoxA genes is
      altered coordinately in response to retinoic acid in a manner consistent with the
      transformation of a distal blastema to a proximal blastema. Given the recent
      increase in studies of the molecules involved in regeneration, it is likely that
      many of the functionally important regeneration genes will be identified and
      characterized in the near future.

PMID- 8877454
TI  - Re-examining jaw regeneration in urodeles: what have we learnt?
AB  - Urodele amphibians can regenerate not only their limbs and tails, but also their
      upper and lower jaws rather faithfully. However, relatively few studies of jaw
      regeneration in amphibians have been carried out, especially in recent years. It
      is therefore important to reexamine thoroughly this regenerating system, since
      the advent of sophisticated morphological techniques and the development of
      molecular approaches offer the promise of renewed and rapid progress in our
      understanding of complex developmental problems such as this. This paper briefly
      reviews some of the early research on jaw regeneration, some of the fundamental
      questions which have been asked and have yet to be answered, and the work we have
      carried out in order to understand the molecular mechanisms underlying jaw
      regeneration in the newt, Notophthalmus viridescens. In addition, some aspects of
      jaw regeneration will be discussed in relation to regeneration of the adult limb.

PMID- 8877455
TI  - Can insights into urodele limb regeneration be achieved with cell cultures and
      retroviruses?
AB  - Recent advances in the field of amphibian limb regeneration have provided
      insights into its cellular and molecular events. This review summarizes the
      development of cell lines from limb tissues and their application to the study of
      transdifferentiation and limb regeneration. In addition, the availability of
      suitable retroviral vectors for salamanders is discussed for it has opened new
      avenues for experimentation at the molecular level.

PMID- 8877456
TI  - Is retinoic acid an endogenous ligand during urodele limb regeneration?
AB  - The effects of retinoids on a regenerating urodele limb make them interesting
      candidates for endogenous ligands during regeneration. We review the evidence for
      considering this possibility. This includes analysis of retinoids and retinoic
      acid receptors in the regenerate, and studies on activation of retinoid reporter
      genes. Recent work has provided evidence that the wound epidermis is a source of
      9-cis retinoic acid, and may be a favorable model for studying the synthesis and
      release of this modulator.

PMID- 8877457
TI  - Spinal cord regeneration: a phenomenon unique to urodeles?
AB  - Studies of neuronal survival and axonal regeneration in birds and mammals have
      made it clear that the microenvironment of the CNS is critical to the failure of
      CNS regeneration in these animals. This environment includes growth and trophic
      factors, ECM components and matrix turnover enzymes, cytokines and other immune
      system contributions. Urodele amphibians (salamanders and newts) can regenerate
      spinal cord even as adults, and environmental contributions of glial populations
      are a major part of the difference between urodele and higher vertebrate spinal
      cord regeneration. In particular, the behavior of injury-reactive ependymal cells
      (radial glia) is critical to the regenerative capacity of urodele spinal cord. In
      this review we examine what is known about cell-cell interactions between
      ependymal cells and neurons and between ependymal cells and other glial
      populations. The known contributions of ependymal cell products such as matrix
      metalloproteinases and trophic factors are discussed. There is evidence in the
      literature that an ependymal response occurs during embryonic or fetal
      development in birds and mammals following spinal cord transection, and this
      review discusses the implications of such a process for future studies of spinal
      cord injury.

PMID- 8877458
TI  - Mechanisms of retina regeneration in urodeles.
AB  - This review is a comparative analysis of retina regeneration in amphibians, fish,
      birds, and mammals. Special attention is given to the newt, which, unlike other
      vertebrates, retains the capacity for the regeneration of eye structures during
      all life. The review focuses on the sources of the cells which contribute to
      retina regeneration, the factors which control the process, and the genes
      expressed during the course of regeneration.

PMID- 8877459
TI  - Evolutionary patterns in ontogenetic transformation: from laws to regularities.
AB  - The concept of heterochrony derives from classical approaches to the study of
      ontogeny and phylogeny. Under the influence of landmark books by deBeer (1930)
      and Gould (1977), the traditional theories have been revised to fit into the
      conceptual framework of modern genetics and evolutionary theory. The current
      scheme, however, suffers from a problem of lack of precise definitions. The term
      heterochrony is now used to refer to a developmental process as well as to an
      evolutionary pattern. That is, it refers to a microevolutionary process of
      adaptation, operating in local populations under selection and to a
      macroevolutionary pattern based on undefined internal laws of form. Such
      conceptually contradictory frameworks are a source of confusion and of empirical
      misuse of concepts. We propose to reduce the dependence of current thinking about
      heterochrony on the concept of "timing" and instead focus on the organization of
      sequences of developmental events in ontogeny. Although Haeckelian views have
      been rejected, most experts would agree that some subtle parallelism between
      ontogeny and phylogeny does occur. This relationship deserves renewed attention
      and urodeles are particularly suited to study it due to their variable patterns
      of ontogeny and complex life cycles. Current reductionist attempts to apply the
      morphological terminology and postulates of classical heterochrony concepts to
      cellular and molecular (genetic) aspects of morphogenesis are problematic.
      Molecular heterochrony requires a linear or strictly hierarchical structure of
      gene regulation of development. In addition, isomorphism between genetic
      mutations and morphological changes would be required for the existing
      terminology to apply. Finally, we caution against a broad interpretation of
      heterochronic processes at the molecular level, since the approach may end up
      permitting the meaningless interpretation of any developmental change as
      heterochrony.

PMID- 8877460
TI  - Direct development in the lungless salamanders: what are the consequences for
      developmental biology, evolution and phylogenesis?
AB  - Direct development is a widespread alternate reproductive mode in living
      amphibians that is characterized by evolutionary loss of the free-living, aquatic
      larval stage. Courtship, mating, and oviposition occur on land, and the
      terrestrial egg hatches as a fully formed, miniature adult. While it is the most
      common reproductive mode in urodeles, development outside the reproductive tract
      of the female that proceeds directly to a terrestrial hatchling occurs in only a
      single lineage, the lungless salamanders of the family Plethodontidae. Evolution
      of direct development in plethodontids has contributed importantly to the
      extraordinary evolutionary success of this speciose, geographically widespread,
      and morphologically and ecologically diverse taxon. Developmental consequences
      and correlates include increased egg size and embryonic development time, loss of
      larval structures and ontogenetic repatterning, and altered pattern formation in
      organogenesis. Evolutionary and phylogenetic consequences and correlates include
      the loss of larval constraints and origin of morphological novelty, and frequent
      homoplasy. Analysis of direct development in an evolutionary context illustrates
      the complex interplay between processes of phylogenetic divergence and
      developmental biology, and substantiates the prominent role of developmental
      processes in both constraining phenotypic variation and promoting phenotypic
      diversity. Despite the proven suitability of direct-developing plethodontid
      salamanders for laboratory and field study, knowledge of basic features of their
      developmental biology remains far below that available for many other urodeles.
      Examination of such features of these "non-model" organisms is an appropriate and
      deserving goal of future research.

PMID- 8877462
TI  - What insights into the developmental traits of urodeles does the study of
      interspecific hybrids provide?
AB  - Natural and artificial hybrids represent an important source of material for
      developmental and evolutionary studies of urodeles. We review the available
      literature on hybrid salamanders, emphasizing the unique developmental insights
      that these organisms provide. Of particular interest is the application of new
      molecular tools to identify DNA markers for traditional characters in
      developmental research, and we discuss our own results using Bulk Segregant
      Analysis to identify RAPD markers for the white phenotype in the axolotl. We pay
      particular attention to the inferences that can be drawn from the many disparate
      crosses between ambystomatid salamanders that vary in their metamorphic response.
      These crossing experiments suggest that 1) metamorphosis is dominant to
      paedomorphosis, 2) that different ambystomatids use different genetic mechanisms
      to block metamorphosis and become sexually mature, larval paedomorphs, and 3)
      metamorphosis may be controlled by a few genetic loci. As increasingly
      sophisticated molecular approaches are applied to these and other hybrid crossing
      schemes, it should be possible to understand the mechanistic basis of a wide
      variety of developmental characters that differentiate urodele species.

PMID- 8877461
TI  - Salamander pigment patterns: how can they be used to study developmental
      mechanisms and their evolutionary transformation?
AB  - Neural crest cells of ectothermic vertebrates give rise to three types of pigment
      cells: melanophores, xanthophores, and iridophores. In early larval salamanders,
      these cells can combine to generate a variety of pigment patterns across taxa,
      including vertical bars and horizontal stripes. Such patterns offer an
      opportunity to study neural crest morphogenesis and differentiation, as well as
      the evolution of these processes and the morphologies that arise from them. This
      review examines the phylogenetic distribution of specific pigment patterns, our
      current understanding of the mechanisms underlying these patterns, and how
      evolutionary transformations of these mechanisms may have resulted in alternative
      pigment patterns across taxa.

PMID- 8877463
TI  - Axolotls in the second grade.

PMID- 8877464
TI  - A laboratory classroom exercise: cell migration in cutaneous wound healing and
      pigmentary pattern formation in the red-spotted newt.

PMID- 8877465
TI  - Urodele (e.g., axolotl) embryos in the undergraduate laboratory class: an essay
      describing a multifaceted learning experience.

PMID- 8877466
TI  - A method for the isolation and culture of embryonic cardiomyocytes from Mexican
      axolotl.

PMID- 8877467
TI  - Treatment of axolotls with retinoids for limb regeneration studies.

PMID- 8877468
TI  - Techniques for obtaining and raising plethodontid salamander eggs.

PMID- 8877469
TI  - How to observe surface contraction waves on axolotl embryos.

PMID- 8877470
TI  - A phase I/II study to evaluate radiation therapy and hyperthermia for deep-seated
      tumours: a report of RTOG 89-08.
AB  - The purpose of this paper is to evaluate the safety and efficacy of deep
      hyperthermia in conjunction with radiation therapy. This study employed 'second
      generation' electromagnetic devices which were felt to be better able to confine
      heating and spare normal tissue than the devices evaluated in a previous study
      (RTOG 84-01). Sixty six patients at six institutions were enrolled on a
      prospective Phase I/II study. Eligible deep seated tumours were treated with a
      combination of external hyperthermia and radiation therapy. Radiation consisted
      of 1.7-2 Gy per fraction, 4-5 fractions per week, to > 20 Gy (previously
      irradiated lesions) or > 50 Gy (no previous radiation). Deep hyperthermia was
      delivered with electromagnetic devices: BSD 2000 for 92% of cases, Thermotron for
      5% of cases, other low frequency electromagnetic for 4% of cases. Hyperthermia
      was delivered < or = twice weekly. Overall complete and partial response rates
      were 34% and 16% respectively. Response was not correlated with maximum tumour
      temperature or disease site. There was, however, a strong association with
      radiation dose: 54% CR with > or = 45 Gy versus 7% with < 45 Gy (p < 0.0001). The
      achieved temperatures were less than ideal. Although the average maximum tumor
      temperature was 41.9 degrees C (range 35.7 degrees C-46.7 degrees C), the minimum
      tumour temperatures were low. The average minimum tumour temperature was 38.5
      degrees C and was never > 41.8 degrees C. Treatment was well tolerated with no
      fatalities. There were four acute grade 3 or 4 toxicities (6% of patients).
      Patient discomfort resulted in interruption or discontinuation of sessions in 30%
      of the sessions. In 12 cases (18% of patients) the planned course of hyperthermia
      was discontinued due to acute discomfort. The devices used in this study were
      better tolerated than the devices used in the previous Phase I/II deep
      hyperthermia trial (RTOG 84-01) with less patient discomfort and no problems with
      severe systemic cardiovascular stress. In the previous study 68% of the
      hyperthermia courses were prematurely terminated primarily due to patient
      discomfort and toxicity; in the present study 18% were prematurely terminated.
      However, as indicated by the low minimum tumour temperature, fundamental problems
      with achieving acceptable temperature distributions remain.

PMID- 8877471
TI  - Cerebral bloodflow in and around spontaneous malignant gliomas.
AB  - Knowledge of the cerebral bloodflow (CBF) in and around malignant gliomas is of
      crucial importance in developing strategies for hyperthermia-, radiation-, and
      chemo-therapy of these difficult to cure lesions. To gather data regarding this
      important physiological variable, the perfusion distributions of 26 patients who
      had either a glioblastoma multiforme or an anaplastic astrocytoma were determined
      using stable xenon computed tomography (XeCT). Perfusion values were determined
      for each of the following anatomical regions: low density tumour core, the
      enhancing active ring of the tumour, the low density peripheral region of edema,
      an ipsilateral region of normal brain adjacent to the tumour, and a region of
      remote normal tissue on the contralateral side of the brain. A multiple
      regression analysis of the logs of the CBF values was used to analyse: (1) the
      differences in blood perfusion between the anatomical regions; and (2) the
      association of blood perfusion with various patient and tumour characteristics.
      Statistically significant differences in perfusion values were found between all
      of the anatomically outlined regions with the exceptions that the active tumour
      and edematous regions do not differ significantly from the ipsilateral normal
      brain tissue. The ipsilateral normal brain tissue adjacent to the tumour was
      found to have a relative perfusion (relative to the contra-lateral normal brain
      tissue perfusion) of 0.84, the edematous tissue had a relative perfusion of 0.52,
      the active tumour 0.78, and the core 0.39. Significant blood flow was present in
      the low density tumour core, contradicting the frequent assumption that there is
      zero or minimal blood flow in such regions. Multiple regression analysis was used
      to look for other variables that might be associated with blood flow after
      adjusting for the differences between anatomical regions. This analysis found a
      significant negative correlation between tumour blood-flow and tumour volume. It
      also estimated that blood flow in GMB tumours was approximately 67% of that in
      lower grade tumours. Variables that were found not to be significantly correlated
      with blood flow were: patient sex, multiple lobe involvement, hemisphere
      involved, treatment status (initial vs recurrent disease), Karnofsky performance
      status, age and, lobe involved.

PMID- 8877472
TI  - Simulation studies promote technological development of radiofrequency phased
      array hyperthermia.
AB  - A treatment planning program package for radiofrequency hyperthermia has been
      developed. It consists of software modules for processing three-dimensional
      computerized tomography (CT) data sets, manual segmentation, generation of
      tetrahedral grids, numerical calculation and optimisation of three-dimensional E
      field distributions using a volume surface integral equation algorithm as well as
      temperature distributions using an adaptive multilevel finite-elements code, and
      graphical tools for simultaneous representation of CT data and simulation
      results. Heat treatments are limited by hot spots in healthy tissues caused by E
      field maxima at electrical interfaces (bone/muscle). In order to reduce or avoid
      hot spots suitable objective functions are derived from power deposition patterns
      and temperature distributions, and are utilised to optimise antenna parameters
      (phases, amplitudes). The simulation and optimisation tools have been applied to
      estimate the improvements that could be reached by upgrades of the clinically
      used SIGMA-60 applicator (consisting of a single ring of four antenna pairs). The
      investigated upgrades are increased number of antennas and channels (triple-ring
      of 3 x 8 antennas and variation of antenna inclination. Significant improvement
      of index temperatures (1-2 degrees C) is achieved by upgrading the single ring to
      a triple ring with free phase selection for every antenna or antenna pair.
      Antenna amplitudes and inclinations proved as less important parameters.

PMID- 8877473
TI  - Dependence of proton generation on aerobic or anaerobic metabolism and
      implications for tumour pH.
AB  - Since low intracellular pH potentiates the hyperthermia response, the number of
      protons generated within the cell is calculated for both aerobic and anaerobic
      metabolism. The calculations incorporate the most recent estimates for the P: O
      ratio in mitochondrial oxidative phosphorylation, and include the hydrolysis of
      ATP as well as its synthesis. Anaerobic glycolysis of glucose to lactate
      generates two proton equivalents per mol of glucose, due to the complete
      dissociation of lactic acid. This corresponds to 1.00 proton per ATP, and is
      independent of pH. For aerobic metabolism of glucose to CO2 and water, protons
      are generated in the cell by dissociation of carbonic acid, and the exact number
      depends upon cytosolic pH. In the physiological pH range, one finds 4.1-5.9 mol
      of hydrogen ion per mol of glucose, which corresponds to 0.14-0.20 per ATP. Thus,
      anaerobic metabolism generates 5-7x as much acid within the cell as aerobic
      metabolism if the two are operating at the same rate in terms of ATP generation
      per unit time.

PMID- 8877474
TI  - Tumour-growth inhibition by induced hyperglycaemia/hyperlactacidaemia and
      localized hyperthermia.
AB  - The present study was undertaken to exploit pathophysiological properties of
      solid tumours for a tumour-specific therapy. Experiments were carried out on DS
      sarcomas implanted s.c. in the hind foot dorsum of Sprague Dawley rats. Treatment
      strategies included tumour acidification, lactate accumulation and disturbance of
      the microcirculation by induced systemic hyperglycaemia/hyperlact-acidaemia (15
      25/10 mmol/L; for 60 min) as well as localized hyperthermia (water-bath; 43
      degrees C, 30 min.). A special infusion solution was developed for the systemic
      treatment containing glucose, lactic acid and organic buffer without inorganic
      ions. Growth kinetics of tumour volume and animal survival were taken as
      endpoints in order to quantify therapeutic efficiency. After a single treatment
      with combined modalities, i.e., with hyperglycaemia/hyperlactacidaemia and
      hyperthermia, approximately 50% of the tumours showed complete remission in three
      independent series of experiments; around 40% of the animals survived more than
      two months. In the untreated control group, all animals died from the disease
      within 10-15 days after tumour implantation. The overall effect on tumour volume
      changes of the combined therapy was supra-additive compared to that of treatment
      with hyperthermia or hyperglycaemia/hyperlactacidaemia alone. However, treated
      animals either showed a dramatic response to the combination of treatments with
      complete tumour remission or hardly responded at all, justifying a subdivision
      into responders and non-responders. Pathophysiological mechanisms responsible for
      this behaviour have to be elucidated in future studies. Nevertheless, the present
      study represents an approach to an efficient tumour therapy with a potential
      application in clinical oncology in the not too distant future.

PMID- 8877475
TI  - Garlic preserves patency and delays hyperthermia-induced thrombosis in pial
      microcirculation.
AB  - Three trials were carried out to study the effect of garlic on thrombus formation
      and patency in the mouse pial microcirculation in response to hyperthermia. Two
      different hyperthermic exposures, at 43 degrees C for 60 min and at 44 degrees C
      for 45 min, were applied to the brain surface of anaesthetized mice by heated
      artificial cerebrospinal fluid (ACSF). Garlic solutions were prepared 24 h prior
      to their injection, i.p., from a finely-ground powder in saline (pH 7.3) to
      deliver doses of 25, 50 and 75 mg/kg. Control groups of the three trials were
      injected with saline, pH 7.3. Garlic and vehicle solution injections were made 60
      min prior to the intended hyperthermic exposure. Microvascular responses were
      monitored and were recorded by intravital videomicroscopy. With core body
      temperature kept at 37 degrees C and at the elevated ACSF temperatures, the first
      observed intravascular response was in the form of either passing emboli or as
      visible thrombosis in either arterioles or venules. Further thromboembolic events
      continued and throughout such exposures higher arteriolar patency was evident in
      the garlic-treated mice. Collectively, garlic significantly delayed the
      appearance of the first observable thrombo/embolic response. Data of this study
      evidenced that garlic delayed hyperthermia-induced platelet aggregation, in vivo.
      Such results could prove beneficial to those adversely affected by antithrombotic
      drugs, like aspirin.

PMID- 8877476
TI  - Hyperthermia decreases cytokine-mediated adhesion molecule expression on human
      umbilical vein endothelial cells.
AB  - Although hyperthermia has been used as an effective cancer treatment modality,
      its effects on metastasis of tumour cells are not clear. Since adhesion molecules
      play a key role in metastasis, we evaluated how the expression of adhesion
      molecules is influenced by hyperthermia. Human umbilical vein endothelial cells
      were incubated in vitro for 1 h. at 39, 42, 43 and 44 degrees C with and without
      addition of tumour-necrosis factor (TNF) or interferon-gamma (IFN-gamma) and the
      expression of endothelial cell leukocyte adhesion molecule-1 (ELAM-1),
      intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex
      (MHC) class-II molecule was measured. Expression of MHC class-II molecules and
      expression of unstimulated constituent ICAM-1's was not reduced by heat
      treatment. In contrast, expression of cytokine-induced ELAM-1's and ICAM-1's was
      significantly lower after heat treatment. The adhesion to HUVEC in vitro of HL-60
      leukemia cells, which express sialyl-Lewis-x antigen as a ligand to ELAM-1, was
      diminished after incubation at 42 degrees C and totally lost after treatment at
      44 degrees C. This suggests that any decrease in metastasis formation after heat
      treatment, which is occasionally observed, could be due to a reduced action of
      TNF or related cytokines on adhesion molecule induction and subsequent membrane
      expression by the endothelial cell. A possible underlying mechanism involved is a
      heat-induced alteration or blockage of the biosynthetic pathways required for
      synthesis of ELAM-1 and ICAM-1 proteins.

PMID- 8877477
TI  - Expression of melanoma-associated antigen of thermotolerant human cells.
AB  - The expression of the melanoma-associated antigen p250 on thermotolerant cells
      and the effect of a second heat dose on the antigen expression have been measured
      by flow cytometry. The human melanoma cell line FME was heated at 43.5 degrees C
      for 120 min after a priming heat dose at 43.5 degrees C for 20, 40 or 60 min.
      Cells preheated at 43.5 degrees C for 40 and 60 min followed the same kinetics of
      development and decay of thermotolerance, with maximum thermotolerance 16 h after
      the priming heating, and the thermotolerance had decayed by 48 h. Cells preheated
      at 43.5 degrees C for 20 min showed maximum thermotolerance after 7 h and decay
      by 24 h. Heat reduced the expression of the melanoma-associated antigen in a dose
      dependent manner. Thermotolerant cells were given a second heat dose (43.5
      degrees C for 120 min) and the antigen expression measured immediately after
      heating. Fractionated hyperthermia using the lower predose (43.5 degrees C for 20
      min) might have an additive effect on the reduction of antigen expression, while
      the highest predose (43.5 degrees C for 60 min) protected against reduction in
      antigen expression. The development and decay of resistance against heat-induced
      reduction in expression of melanoma-associated antigen followed a similar time
      course as thermotolerance in terms of cell survival. Maximum resistance was
      observed 12 h after the priming heat treatment, and the resistance had decayed by
      48 h.

PMID- 8877478
TI  - Reduction of etoposide induced cell killing by hyperthermia can occur without
      changes in etoposide transport or DNA topoisomerase II activity.
AB  - We investigated the modification of etoposide (i.e. VP-16)-induced cell killing
      by hyperthermia in a radioresistant human melanoma (Sk-Mel-3) and a human normal
      (AG1522) cell line. VP-16, a DNA topo II poison, was given as a 1 h exposure at
      variable doses up to 35 microM; hyperthermia was given either before or following
      VP-16 treatment. Hyperthermic treatment comprised one of the following: 41
      degrees C for 8 h, 42 degrees C for 2 h or 45 degrees C for 15 min. Hyperthermia
      preceding VP-16 treatment reduced the cytotoxicity of the latter; the reduction
      of VP-16 cytotoxicity was directly proportional to the severity of the
      hyperthermic treatment. For a particular combination of hyperthermic dose and VP
      16 concentration, generally similar responses were seen in both cell lines. There
      were no effects on VP-16 cytotoxicity when both Sk-Mel-3 and AG1522 cells were
      heated at 41 degrees C for 8 h following treatment with VP-16. However, heating
      both cell lines at 45 degrees C for 15 min following VP-16 treatment again
      reduced the amount of cytotoxicity associated with VP-16. In addition, we found
      that a preceding exposure to 45 degrees C, 15 min heating did not affect either
      cellular accumulation or efflux of [3H]VP-16 in both cell lines. This suggested
      that the reduction in VP-16 cytotoxicity observed under those conditions was not
      due to a modification of VP-16 transport. We found no differences between the
      catalytic activities of topo II extracted from nuclei of Sk-Mel-3 and AG1522
      cells that were either heated at 45 degrees C for 15 min or that were not
      subjected to such treatment. These results therefore suggested that the
      substantial reduction of cytotoxicity seen when 45 degrees C, 15 min heating
      preceded VP-16 treatment was also not due to an effect on topo II catalytic
      activity. Our results therefore demonstrate that hyperthermia, given either
      before or after VP-16, can actually reduce the amount of VP-16 cytotoxicity and
      that this can occur without any overt changes in VP-16 accumulation and efflux or
      in topo II catalytic activity.

PMID- 8877480
TI  - The WHO Program on Mental Health Behavioral Science Learning Modules.

PMID- 8877479
TI  - Safe and efficient extracorporeal method of inducing whole body hyperthermia.

PMID- 8877481
TI  - Psychiatry and primary care: closing the gap.

PMID- 8877482
TI  - Psychiatry and primary care as neighbors: from the Promethean primary care
      physician to multidisciplinary clinic.
AB  - OBJECTIVE: A successful eight-year experience developing a co-practice model for
      psychiatry in a primary care practice is described. METHODS: The effect on
      service delivery of specific changes in availability, shared location, and
      consistency of interdisciplinary relationships are discussed. RESULTS: The
      following components of successful collaboration were identified: 1) The
      importance of fiscal organization and leadership factors in creating a successful
      bridge between psychiatry and primary care. 2) How individual tailoring for the
      setting (rural vs. urban) affects the collaboration. 3) Adaptations incumbent
      upon psychiatrists to function well in such settings. 4) The development of a
      teaching program and training track for medical and psychiatric housestaff in
      such settings. CONCLUSIONS: Making psychiatry accessible at the front line of
      primary care enhances delivery of care and does not detract from any service.

PMID- 8877483
TI  - Overcoming barriers to teaching medical housestaff about psychiatric aspects of
      medical practice.
AB  - OBJECTIVE: This article describes a training program in psychiatric aspects of
      medical practice. It is aimed at medical residents. METHODS: Six fundamental
      elements have been identified that contribute to the effectiveness of this
      program. 1) It directly confronts resistance to such training. 2) Practical
      skills are emphasized. 3) Learning is active. 4) Attention to group process
      during training is used. 5) Integration by on-site location of the psychiatrist
      and co-teaching with medical faculty is essential. 6) Teaching efforts are
      integrated with clinical service. RESULTS: All 112 medical housestaff participate
      in the program with a generally enthusiastic response. CONCLUSIONS: Successful
      educational programs for primary care residents require teaching collaboration
      between psychiatric and medical faculty and impart specific clinical skills while
      addressing perceived burdens of time and emotional reactions.

PMID- 8877484
TI  - Consultation-liaison psychiatry fellowship in primary care.
AB  - OBJECTIVE: This article describes the need for and development of an outpatient
      primary care psychiatry fellowship program. METHOD: The Department of Psychiatry
      at Hillside Hospital established a primary care fellowship for psychiatrists in
      1994, through its consultation-liaison (C-L) service. Staff alliances established
      by the C-L service with primary care physicians provided the basis for
      identifying appropriate outpatient practices in the community. Knowledge and
      skills objectives were adapted from a traditional C-L fellowship to outpatient
      primary care medicine. RESULTS: The selection of a psychologically minded primary
      care practitioners was crucial. Practitioners used an inclusive model in which
      fellows would see all patients with them, not just those with mental disorders.
      Fellows have felt comfortable working in the primary care setting and have been
      well received by practitioners, staff, and patients. The practitioners were
      clearly more interested in psychosocial aspects of their patient than were
      primary care residents. CONCLUSIONS: The gap in preparing U.S. psychiatrists to
      function in integrated primary care programs requires establishing a presence in
      the primary care setting. Skills and relationships from traditional C-L settings
      can be productively used to accomplish this goal.

PMID- 8877485
TI  - Geriatric psychiatry at the interface of consultation-liaison psychiatry and
      primary care.
AB  - OBJECTIVE: This article describes the evolution of a primary care geriatric
      psychiatry program which serves clinical, educational, and research functions.
      METHODS: Program development proceeded through stages of liaison using research,
      focusing on primary care attendings, and developing the common interest of
      geriatrics. RESULTS: Collaborative research with external funding has continued.
      A geriatric psychiatry primary care fellowship program was established. Clinical
      activity is based on consultation-liaison work in nursing homes, an outpatient
      dementia clinic, a general hospital medical service, and the outpatient clinic.
      Fellows are involved in training both psychiatry and primary care residents.
      CONCLUSIONS: Necessary components of a successful collaboration include: 1)
      primary care physicians with an interest in and aptitude for psychiatric issues;
      2) delivery of service and training based on an assessment of the primary care
      site's needs; 3) a physical presence in the primary care site.

PMID- 8877486
TI  - The recognition and treatment of late-life depression: a view from primary care.
AB  - OBJECTIVE: Efforts to improve the recognition and treatment of late-life
      depression in primary care are often based on the assumption that primary care
      physicians underutilize currently available and effective treatments. This
      article reviews the validity of this assumption and offers recommendations for
      future research. METHODS: Clinical trials designed to improve the recognition and
      treatment of late-life depression in primary care are reviewed. Because studies
      limited to older adults are rare, we also include studies enrolling younger
      patients. These data are reviewed in the context of recent reviews on the
      prevalence of depression in primary care settings and the effectiveness of
      available treatments. RESULTS: Although depressive symptoms are common among
      older adults, there is insufficient literature documenting the proportion of
      these patients who respond to currently available treatments. Patients with
      uncomplicated major depressive disorder constitute the minority of primary care
      patients with depressive symptoms. Nearly all available studies of treatment
      effectiveness of pharmacotherapy or psychotherapy focus on older adults with
      uncomplicated major depression. Currently available treatment options may apply
      to less than 15 percent of depressed primary care patients. CONCLUSIONS: More
      research is needed to help primary care providers manage their depressed patients
      with comorbid medical conditions, functional disability, or minor or chronic
      depressions. In addition, more research is needed to identify those patients who
      would benefit from specialized or interdisciplinary care.

PMID- 8877487
TI  - Minor depression: a review of the literature.
AB  - OBJECTIVE: The clinical experience of the authors has suggested there is a
      significant group of elderly and individuals with medical illness and depressive
      symptoms who do not meet DSM-IV criteria for major depression. We were interested
      in all available data regarding minor depression in both the medically ill and
      community individuals. METHODS: MEDLINE was searched from 1965 to 1995, using the
      terms "depressive disorders" and "medical illness," as well as "atypical
      depression" and "elderly." Relevant references from these primary articles were
      also utilized. RESULTS: In medical patients, depressive symptoms were associated
      with decreased likelihood of discharge to home. Although diagnostic criteria
      vary, some suggest anhedonia as the central feature. From 3 to 16 percent of
      medical outpatients suffer from minor depression. Up to 64 percent of medical
      inpatients will complain of depressed mood. Studies in community samples found
      that minor depression was responsible for 9 to 16 percent of total disability
      days, and was associated with absenteeism from work, as well as separation and
      divorce. Little is known about the natural history and prognosis of minor
      depression. CONCLUSIONS: Minor depression is both common and has a significant
      impact on the health care system, and therefore deserves further study.

PMID- 8877488
TI  - Stressful life events and minor psychiatric disorders: an estimate of the
      population attributable fraction in a Brazilian community-based study.
AB  - OBJECTIVE: A population-based survey was conducted in Pelotas, southern Brazil,
      to assess the specific and the combined contribution of life events and
      socioeconomic factors on the overall prevalence of minor psychiatric disorders
      (MPD). METHODS: The study covered a representative sample of the population aged
      fifteen years or older living in the urban area of the city. Using multi-stage
      sampling, a total of thirty census tracts and 600 households were selected. A
      standardized questionnaire assessed the presence of MPD (using the Self-Reporting
      Questionnaire-SRQ-20), the occurrence of life events (death of a relative, a
      relative with a chronic disease, loss of employment, divorce, migration,
      accident, and robbery/assault), and socioeconomic factors. RESULTS: The
      prevalence of MPD was 22.7 percent (17.9% males and 26.5% females) and increased
      with age. Significant linear relationships with education and income were
      observed: the less education and income, the higher the prevalence of MPD. All
      life events, except migration and accident, were positively associated with MPD.
      People who experienced divorce in the last year had a prevalence of MPD three
      times higher than those who had not. The likelihood of MPD increased linearly
      with the number of life events. The highest proportion of Population Attributable
      Fraction for any life events was 24 percent. CONCLUSIONS: These data suggest that
      life events can explain a substantial proportion of MPD and with socioeconomic
      factors may be related to the onset of MPD.

PMID- 8877489
TI  - Psychiatric consultation for somatizing patients in the family practice setting:
      a feasibility study.
AB  - OBJECTIVE: The purpose of the study was to assess the feasibility of a
      psychiatric consultation intervention for somatizing patients in the family
      practice setting in terms of 1) patient compliance, 2) patient satisfaction, and
      3) compliance and satisfaction of general practitioners (GPs). METHOD: In a
      period of nine months, forty-six patients were selected for psychiatric
      consultation in six solo family practices in a semi-urban area in the
      Netherlands. The consultation included an interview with the consulting
      psychiatrist, the patient, and the GP. A written summary of the consultation was
      provided to the GP and the patient. A booster session with a GP and psychiatrist
      was included to evaluate and reinforce the recommendations. RESULTS: The majority
      of the selected patients agreed to participate after informed consent. An
      intervention was implemented containing interpersonal techniques, reattribution,
      clarification, and structuring. GP compliance with recommendations was 100
      percent, patient compliance 75 percent. CONCLUSION: A standardized psychiatric
      consultation for somatizing patients in a family practice setting can be
      implemented. Several levels of implementation can be distinguished.

PMID- 8877490
TI  - Keratinization and necrosis. Morphologic aspects of lymphatic metastases in
      ultrasound.
AB  - RATIONALE AND OBJECTIVE: The authors performed a retrospective study in
      ultrasound to investigate new aspects in the sonomorphology of lymph node
      metastases of the neck. In this study, it could be demonstrated the first time
      that the histologic characteristics of the metastases determine the sonographic
      appearance. In addition to criteria such as the longitudinal/ transversal
      quotient, sonomorphology could support a more precise differential diagnosis of
      neck lymph nodes. METHODS: In 105 of 145 patients with histologically proved head
      and neck carcinomas, 187 lymph node metastases were detected by ultrasound.
      Sonomorphology was compared with the corresponding histology. RESULTS: Five
      sonomorphologic groups could be differentiated. (1) Thirty-one percent of the
      metastases were homogenous. (2) Concerning the more complex morphology of lymph
      node metastases in ultrasound, echolucent forms could be differentiated from
      echogenic textures: low- or nondifferentiated and nonkeratinizing metastases
      appeared echolucent and cyst-like, with dorsal signal amplification. (3)
      Nonkeratinizing lymphomas with necrosis showed single or multiple echolucent
      intranodal lesions. (4) In correlation with an increasing keratinization, the
      echogenecity of the lymph nodes increased and intranodal echogenic inclusions
      appeared. (5) An extended keratinization correlated with a central echogenecity.
      CONCLUSIONS: The morphologic assessment of lymph nodes in ultrasound allows for
      primary histologic and prognostic evaluation of lymph node metastases.

PMID- 8877491
TI  - An experimental study on the neurotolerability of gadobenate dimeglumine in a rat
      model of focal brain ischemia.
AB  - RATIONALE AND OBJECTIVES: The neurologic safety of the new magnetic resonance
      imaging contrast agent gadobenate dimeglumine has been assessed in rats suffering
      from localized blood-brain barrier damage. METHODS: The adopted experimental
      model was the photochemically induced brain ischemia in the rat. Flash-evoked
      visual potentials were recorded simultaneously from the damaged area and from the
      corresponding contralateral position in conscious rats before and after the
      administration of the contrast medium. RESULTS: The intravenous administration of
      0.9 mmol/kg of gadobenate dimeglumine did not induce any significant changes in
      the visual responses recorded from the ischemic side compared with the intact
      side. Rats treated with saline or with the reference compounds gadopentetate
      dimeglumine (Magnevist) and gadoteridol (ProHance) gave comparable results.
      CONCLUSIONS: The results are in favor of the use of gadobenate dimeglumine in
      patients suffering from a localized damage to blood-brain barrier.

PMID- 8877493
TI  - Robustness of computerized identification of masses in digitized mammograms. A
      preliminary assessment.
AB  - RATIONALE AND OBJECTIVES: The authors assess the robustness of a computer-aided
      diagnosis (CAD) scheme with five rule-based stages to identify regions suspicious
      for mass in digitized mammograms. METHODS: With a database of 428 mammograms, 234
      of which had not been analyzed by this scheme before, the authors evaluated the
      performance robustness of their CAD scheme. The following four issues were
      investigated to assess the variability of the scheme's performance due to: (1)
      the maximum permissible number of "masses" detected at each stage; (2) exclusion
      of selected individual rule-based stages; (3) added image noise; and (4) repeated
      digitizations of the same image. RESULTS: Enabling the CAD scheme to select a
      maximum of two suspicious mass regions at any one stage increased sensitivity by
      as much as 4% (from 93% to 97%), but it increased the false-positive detection
      rate by as much as 1.2 per image (from 1.7 to 2.9). Eliminating any individual
      stage decreased sensitivity by as much as 6%, but this reduced the false-positive
      detection rate by as much as 0.4 per image (from 1.7 to 1.3). The addition of
      reasonable noise levels decreased sensitivity by as much as 4% without
      substantially affecting the false-positive detections. Repeated digitizations of
      selected images demonstrated a scheme sensitivity of 93% +/- 1.8% with more than
      a 90% overlap of the false-positive regions. CONCLUSIONS: The results of this
      preliminary study clearly indicate that this scheme is reasonably robust to the
      variables investigated here.

PMID- 8877492
TI  - Investigations into the mechanisms of coronary vasodilation by contrast media in
      dogs.
AB  - RATIONALE AND OBJECTIVES: The study was performed to clarify the mechanisms
      underlying contrast-induced coronary vasodilation. METHODS: The left anterior
      descending coronary artery of 14 open-chest dogs was perfused at constant
      pressure. Coronary blood flow (CBF) was measured electromagnetically and used to
      calculate myocardial oxygen consumption (MVO2). Responses were evaluated during
      intracoronary infusions (2 mL/ minute) of the ionic contrast medium, Hypaque-76,
      and the nonionic contrast medium, Isovue-370, and compared with those caused by
      hypertonic saline solutions with comparable osmolarities. Studies also were
      conducted using Isovist-300, which is a new nonionic and iso-osmolar contrast
      medium. RESULTS: Hypaque-76 and Isovue-370 caused initial peak increases in CBF
      (reflecting decreases in coronary vascular resistance), which waned rapidly to
      achieve more modest steady-state increases within 2 to 3 minutes. Both the peak
      and steady-state increases in CBF were greater during Hypaque-76 than during
      Isovue-370. The increases in CBF caused by the contrast medium were greater than
      those caused by the corresponding saline solution. Neither Hypaque-76 nor Isovue
      370 changed MVO2-Isovist-300 had no effect on CBF or MVO2. CONCLUSIONS: The
      coronary vasodilation by contrast media is the result of a direct vasorelaxing
      effect rather than secondary to a metabolic mechanism. Hyperosmolarity can
      account only in part for contrast-induced coronary vasodilation.

PMID- 8877494
TI  - Correlation of some geometric parameters derived from molecular models of monomer
      nonionic contrast medium molecules with their octanol/water partition
      coefficient.
AB  - RATIONALE AND OBJECTIVES: The author geometrically quantifies the concept of
      hydrophilic facial and lateral protection of the benzene ring in nonionic monomer
      contrast medium molecules and verifies the validity of its incorporation in the
      design theory. The author also correlates this quantification with the
      octanol/water partition coefficient. METHODS: Six monomer nonionic contrast
      medium molecules were studied using simple measuring techniques with respect to
      some geometric parameters quantifying the hydrophilic protection of the
      hydrophobic zones. The results were processed to obtain a quantifying parameter,
      which was correlated subsequently with the corresponding octanol/water partition
      coefficients. RESULTS: A high correlation (r = 0.90) of the developed quantifying
      parameter with log-P was calculated; its reliability is high. CONCLUSIONS: The
      validity of the faciality/laterality concept and of its incorporation in the
      design theory was shown.

PMID- 8877495
TI  - Analysis of three-dimensional computerized representations of articular cartilage
      lesions.
AB  - RATIONALE AND OBJECTIVES: The authors assess the accuracy of three-dimensional
      (3D) computer representations based on magnetic resonance images of articular
      cartilage lesions, using actual cartilage lesions as reference standards.
      METHODS: Grade 2 and grade 3 articular lesions were created on articular surfaces
      of five porcine knee joints. The knees were then imaged using 3D fat-suppressed
      SPGR acquisition at four different slice thicknesses. Magnetic resonance imaging
      data sets were transferred to a computer workstation for image processing and 3D
      reconstruction. Lesion dimensions (length, width, and depth) based on the 3D
      reconstructed image were compared with the dimensions measured using actual
      lesions. RESULTS: The average percent error of lesion length, width, and depth
      based on the 3D images ranged from approximately 8% to 12% when using the
      thinnest magnetic resonance slice thickness (0.7 mm). CONCLUSIONS: Three
      dimensional reconstructed images derived from thin-slice magnetic resonance
      imaging can provide reasonable representations of true articular cartilage lesion
      dimensions.

PMID- 8877496
TI  - Effects of a 1.5-Tesla static magnetic field on spermatogenesis and embryogenesis
      in mice.
AB  - RATIONALE AND OBJECTIVES: There is a trend toward the use of higher magnetic
      field strengths in magnetic resonance imaging procedures. Considering this trend
      and the lack of consensus on the biologic effects of static magnetic fields, it
      is of considerable interest to examine the biologic effects of a 1.5-tesla (T)
      static magnetic field on spermatogenesis and embryogenesis in mice. METHODS: Male
      and pregnant female Swiss Webster mice were exposed to a 1.5-T static magnetic
      field for 30 minutes. Effects on spermatogenesis in male mice were investigated
      by counting testicular spermheads and epididymal spermhead shape-abnormalities as
      a function of time after exposure. Pregnant female mice were exposed to the field
      at the two-cell embryo stage, sacrificed immediately, and the ability of these
      preimplantation embryos to mature into blastocysts was examined in vitro.
      RESULTS: Exposure to the static 1.5-T magnetic field caused a statistically
      significant reduction (15%) in testicular sperm on the 16th and 29th days after
      exposure. However, the increase in spermhead shape abnormalities above normal
      control values was minimal. A substantial effect was noted on the development of
      preimplantation embryos with a survival fraction of 0.56 compared with controls.
      CONCLUSIONS: A 30-minute exposure to a 1.5-T static magnetic field appears to
      cause some deleterious effects on spermatogenesis and embryogenesis in mice.

PMID- 8877497
TI  - Radiographic contrast media and the coagulation and complement systems.
AB  - Intravascular contrast agents have several side effects including alterations of
      the hemostasis and the complement system. The effects on these systems may be one
      of the main causes of the "adverse contrast agent reaction." In vitro and in vivo
      evidence is provided that both ionic and nonionic contrast media activate the
      plasma kallikrein with consecutive activation of the factor XII-contact phase and
      stimulation of the bradykinin generation. Furthermore, activation of the
      complement cascade via the classic and the alternative pathways was described to
      a various extent for intravascular application of contrast agents. In non
      reactors, these alterations are transient and only have a limited extent
      indicating that these reactions are within the regulatory capacity of the
      kallikrein-kinin-factor XII system. In reactors, however, significant evidence
      for an extended activation of the kallikrein system is associated with reduced
      levels of C1-esterase inhibitor. Therefore, patients with alterations in these
      systems should be regarded as candidates for adverse contrast agent reactions.
      Furthermore, contrast media influence the blood coagulation, especially in
      contact to artificial surfaces (plastic or glass). In vitro findings suggest that
      there is a broad scope of modifications caused by contrast agents indicating a
      modification of the risk of thromboembolism during angiography. Preliminary data
      suggest that an inhibition of clot formation is more effective with ionic
      compared with nonionic contrast agents. In summary, radiographic contrast agents
      have an impact both on the hemostasis and the complement systems. The effects may
      be of importance for adverse reactions as well as for thromboembolic
      complications during angiography.

PMID- 8877498
TI  - Ultrasound demonstration of gallbladder wall thickening as a method to
      differentiate cirrhotic ascites from other ascites.

PMID- 8877499
TI  - Improving the quality of automatic DNA sequence assembly using fluorescent trace
      data classifications.
AB  - Virtually all large-scale sequencing projects use automatic sequence-assembly
      programs to aid in the determination of DNA sequences. The computer-generated
      assemblies required substantial hand-editing to transform them into submissions
      for GenBank. As the size of sequencing projects increases, it becomes essential
      to improve the quality of the automated assemblies so that this time consuming
      hand-editing may be reduced. Current ABI sequencing technology uses base calls
      made from fluorescently-labeled DNA fragments run on gels. We present a new
      representation for the fluorescent trace data associated with individual base
      calls. This representation can be used before, during, and after fragment
      assembly to improve the quality of assemblies. We demonstrate one such use-end
      trimming of sub-optimal data-that results in a significant improvement in the
      quality of subsequent assemblies.

PMID- 8877500
TI  - The megaprior heuristic for discovering protein sequence patterns.
AB  - Several computer algorithms for discovering patterns in groups of protein
      sequences are in use that are based on fitting the parameters of a statistical
      model to a group of related sequences. These include hidden Markov model (HMM)
      algorithms for multiple sequence alignment, and the MEME and Gibbs sampler
      algorithms for discovering motifs. These algorithms are sometimes prone to
      producing models that are incorrect because two or more patients have been
      combined. The statistical model produced in this situation is a convex
      combination (weighted average) of two or more different models. This paper
      presents a solution to the problem of convex combinations in the form of a
      heuristic based on using extremely low variance Dirichlet mixture priors as part
      of the statistical model. This heuristic, which we call the megaprior heuristic,
      increase the strength (i.e., decreases the variance) of the prior in proportion
      to the size of the sequence dataset. This causes each column in the final model
      to strongly resemble the mean of a single component of the prior, regardless of
      the size of the dataset. We describe the cause of the convex combination problem,
      analyze it mathematically, motivate and describe the implementation of the
      megaprior heuristic, and show how it can effectively eliminate the problem of
      convex combinations in protein sequence pattern discovery.

PMID- 8877502
TI  - Discovering patterns and subfamilies in biosequences.
AB  - We consider the problem of automatic discovery of patterns and the corresponding
      subfamilies in a set of biosequences. The sequences are unaligned and may contain
      noise of unknown level. The patterns are of the type used in PROSITE database. In
      our approach we discover patterns and the respective subfamilies simultaneously.
      We develop a theoretically substantiated significance measure for a set of such
      patterns and an algorithm approximating the best pattern set and the subfamilies.
      The approach is based on the minimum description length (MDL) principle. We
      report a computing experiment correctly finding subfamilies in the family of
      chromo domains and revealing new strong patterns.

PMID- 8877501
TI  - From electron density and sequence to structure: integrating protein image
      analysis and threading for structure determination.
AB  - This paper presents a computational methodology for integrating techniques from
      protein image interpretation and protein sequence threading, applied to the
      problem of structure determination from experimental X-ray crystallographic
      electron density maps. In the proposed architecture, image interpretation of an
      electron density map produces candidate structural segments; threading is applied
      to evaluate these hypothesized segments and thus to constrain the set of possible
      image interpretations. We present the results of experiments designed to test
      ability of the threading module to discriminate between correct and incorrect
      alignments of protein sequences onto structural models derived from protein image
      interpretation. The long-term goal of this research is to improve our ability to
      determine protein structures from crystallographic data, and to further our
      understanding of the underlying relationship between sequence and structure.

PMID- 8877503
TI  - A sequence similarity search algorithm based on a probabilistic interpretation of
      an alignment scoring system.
AB  - We present a probabilistic interpretation of local sequence alignment methods
      where the alignment scoring system (ASS) plays the role of a stochastic process
      defining a probability distribution over all sequence pairs. An explicit
      algorithms is given to compute the probability of two sequences given and ASS.
      Based on this definition, a modified version of the Smith-Waterman local
      similarity search algorithm has been devised, which assesses sequence
      relationships by log likelihood ratios. When tested on classical examples such as
      globins or G-protein-coupled receptors, the new method proved to be up to an
      order of magnitude more sensitive than the native Smith-Waterman algorithm.

PMID- 8877504
TI  - The mathematical model of subtractive hybridization and its practical
      application.
AB  - A novel theory of subtractive hybridization including (or based on) the kinetic
      model of this process was proposed. A computer program modeling the process of
      subtraction was developed. Basing on the theory, a novel method of subtractive
      hybridization was proposed allowing routine comparison of genomes and products of
      genome expression. The method was applied to studies of the genetic mechanisms of
      embryogenesis, regeneration, cell differentiation and tumor transformation.

PMID- 8877505
TI  - Using iterative dynamic programming to obtain accurate pairwise and multiple
      alignments of protein structures.
AB  - We show how a basic pairwise alignment procedure can be improved to more
      accurately align conserved structural regions, by using variable, position
      dependent gap penalties that depend on secondary structure and by taking the
      consensus of a number of suboptimal alignments. These improvements, which are
      novel for structural alignment, are direct analogs of what is possible with
      normal sequences alignment. They are feasible for us since our basic structural
      alignment procedure, unlike others, is so similar to normal sequence alignment.
      We further present preliminary results that show how our procedure can be
      generalized to produce a multiple alignment of a family of structures. Our
      approach is based on finding a "median" structure from doing all possible
      pairwise alignments and then aligning everything to it.

PMID- 8877506
TI  - GeneFisher--software support for the detection of postulated genes.
AB  - When a family of genes from closely related organisms is known, there is a
      certain change to extract the corresponding gene from the genome of another
      related organism. This can be done by polymerase chain reaction, provided that a
      pair of suitable primers can be designed. In contrast to primer design for a
      single, known target sequence, systematic primer design for an unknown target
      given a group of homologues can by no means be done manually. GeneFisher is a
      software tool which automates this task, and takes special care to make the
      impact of the manifold design parameters transparent to the user.

PMID- 8877507
TI  - Ontological foundations for biology knowledge models.
AB  - This paper analyzes the ontological requirements for representing biology
      knowledge, and identifies several areas where current knowledge representation
      (KR) paradigms need to be extended. We focus on the representation of
      experimental materials and methods, and the reasoning task of intelligent
      information retrieval; however, the ontological issues we raise apply to biology
      (and experimental sciences) in general. We have identified two important concept
      types in molecular biology that cause problems for standard knowledge models: 1)
      complex substances such as mixtures and nucleic acid sequences; 2)
      transformations (such as biochemical reactions) that convert one substances into
      another. We describe these problems, propose solutions for some of them, and
      given examples of the need for such knowledge representations in intelligent
      information retrieval.

PMID- 8877508
TI  - Good maps are straight.
AB  - This paper proposes a simplified approach to the assembly of large physical
      genome maps. The approach focuses on two key problems: (i) the integration of
      diverse forms of data from numerous sources, and (ii) the detection and removal
      of errors and anomalies in the data. The approach simplifies map assembly by
      dividing it into three phases-overlap, linkage and ordering. In the first phase,
      all forms of overlap data are integrated into a simple abstract structure, called
      clusters, where each cluster is a set of mutually-overlapping DNA segments. This
      phase filters out many questionable overlaps in the mapping data. In the second
      phase, clusters are linked together into a weighted intersection graph. False
      links between widely separated regions of the genome show up as crooked,
      branching structures in the graph. Removing these false links produces graphs
      that are straight, reflecting the linear structure of chromosomes. From these
      straight graphs, the third phase constructs a physical map. Graph algorithms and
      graph visualization play key roles in implementing the approach. At present, the
      approach is at an early stage of development: it has been tested on real and
      simulated mapping data, and the results look promising. This paper describes the
      first two phases of the approach in detail, and reports on our progress to date.

PMID- 8877509
TI  - A top-down approach to whole genome visualization.
AB  - The investigation of large DNA contigs like complete chromosomes or genomes
      requires novel methods of data visualization. The complex information contained
      in a genome, particularly the relation of its individual genetic elements, needs
      to be accessible in a comprehensive, intelligent and intelligible manner. The
      yeast genome is expected to contain more than 6,000 Open Reading Frames (ORFs).
      As yet, the function of many of these ORFs has not been characterized
      satisfactorily. Also, many ORFs are found to have redundant copies elsewhere in
      the genome that originated from common ancestors. Other genetic elements (e.g.
      Tss, delta-elements, t-RNAs) are present in multiple copies. To visualize these
      relationships, a top-down "genome browser" is introduced that enables inspection
      of genomic data at different levels of abstraction (e.g. chromosomes, coding/non
      coding regions, high/low levels of similarity). This novel tool is a key
      component for the integrated services approach to biological sequence data
      management (Heumann et al. 1995) and is accessible through the world wide web
      (WWW). This work demonstrates how the genome browser visualizes the results of an
      all-against-all comparison of the elements in the yeast genome as a graph.
      Interactive navigational queries across yeast chromosomes along the lines of
      sequence similarity open versatile options for the detailed investigation of
      genome properties. For sequence comparison the hashed position tree HPT (Mewes &
      Heumann 1995) is applied. Sequence similarity relationships are represented using
      the genome similarity graph (GSG) (Heumann & Mewes 1996c).

PMID- 8877510
TI  - A probabilistic classification system for predicting the cellular localization
      sites of proteins.
AB  - We have defined a simple model of classification which combines human provided
      expert knowledge with probabilistic reasoning. We have developed software to
      implement this model and have applied it to the problem of classifying proteins
      into their various cellular localization sites based on their amino acid
      sequences. Since our system requires no hand tuning to learn training data, we
      can now evaluate the prediction accuracy of protein localization sites by a more
      objective cross-validation method than earlier studies using production rule type
      expert systems. 336 E. coli proteins were classified into 8 classes with an
      accuracy of 81% while 1484 yeast proteins were classified into 10 classes with an
      accuracy of 55%. Additionally we report empirical results using three different
      strategies for handling continuously valued variables in our probabilistic
      reasoning system.

PMID- 8877511
TI  - HinCyc: a knowledge base of the complete genome and metabolic pathways of H.
      influenzae.
AB  - We present a methodology for predicting the metabolic pathways of an organism
      from its genomic sequence by reference to a knowledge base of known metabolic
      pathways. We applied these techniques to the genome of H. influenzae by reference
      to the EcoCyc knowledge base to predict which of 81 metabolic pathways of E. coli
      are found in H. influenzae. The resulting prediction is a complex hypothesis that
      is presented in computer form as HinCyc: an electronic encyclopedia of the genes
      and metabolic pathways of H. influenzae. HinCyc connects the predicted genes,
      enzymes, enzyme-catalyzed reactions, and biochemical pathways in a WWW-accessible
      knowledge base to allow scientists to explore this complex hypothesis.

PMID- 8877512
TI  - Inferring relatedness of a macromolecule to a sequence database without
      sequencing.
AB  - Derivation of biological information of a macromolecule isolate based on sequence
      similarity is playing a significant role in numerous areas of biological
      research. However, it is often the case that a researcher obtains more
      macromolecule isolates than can be sequenced practically, due either to the high
      cost of sequencing or lack of specialized equipment and personnel. To overcome
      this difficulty, we study the problem of obtaining biological information (such
      as sequence information) about a macromolecule isolate using only (i) the
      fragmentation pattern of that isolate obtained from digestion with enzymes and
      (ii) a database D of sequences. We investigate a three phase approach to solving
      this problem. In the first phase, we obtain a restriction pattern of the isolate
      while analytically deriving the corresponding restriction maps of the sequences
      in the database. In the second phase, we identify a set S [symbol: see text] D of
      sequences which have restriction maps that are most similar to the unknown
      isolate's restriction pattern. This task is complicated by the fact that we have
      only approximate fragment lengths for the unknown isolate and that we do not know
      the actual ordering of the unknown isolate's fragments. Despite these
      difficulties, we derive experimental results which indicate maximum matching
      techniques are effective in identifying the correct set most of the time. In the
      third phase, we use the set S to infer biological information (such as sequence
      information or hierarchical classification information) about the unknown
      isolate. We demonstrate experimentally that the closeness of the sequences in the
      set S to each other can be used to infer the relatedness of the unknown isolate
      to the sequences of the set S. Furthermore, the confidence of this inferred
      information is strongly correlated to the minimum pairwise relatedness of any two
      elements in S.

PMID- 8877514
TI  - A grammar-based unification of several alignment and folding algorithms.
AB  - We show in this paper that many popular models of folding and/or alignment may be
      described by a new formalism: multi-tape S-attribute grammars (MT-SAG's). This
      formalism relieves the designer of biological models of implementation details
      which may hinder his inventiveness. To complete this formalism, we designed and
      implemented a tool which, given a MTSAG, will output an efficient parser for this
      grammar. We also show that MTSAG's offer a new, efficient and useful way to
      handle stochastic context-free grammars and tools that generate them.

PMID- 8877513
TI  - A generalized hidden Markov model for the recognition of human genes in DNA.
AB  - We present a statistical model of genes in DNA. A Generalized Hidden Markov Model
      (GHMM) provides the framework for describing the grammar of a legal parse of a
      DNA sequence (Stormo & Haussler 1994). Probabilities are assigned to transitions
      between states in the GHMM and to the generation of each nucleotide base given a
      particular state. Machine learning techniques are applied to optimize these
      probabilities using a standardized training set. Given a new candidate sequence,
      the best parse is deduced from the model using a dynamic programming algorithm to
      identify the path through the model with maximum probability. The GHMM is
      flexible and modular, so new sensors and additional states can be inserted
      easily. In addition, it provides simple solutions for integrating cardinality
      constraints, reading frame constraints, "indels", and homology searching. The
      description and results of an implementation of such a gene-finding model, called
      Genie, is presented. The exon sensor is a codon frequency model conditioned on
      windowed nucleotide frequency and the preceding codon. Two neural networks are
      used, as in (Brunak, Engelbrecht, & Knudsen 1991), for splice site prediction. We
      show that this simple model performs quite well. For a cross-validated standard
      test set of 304 genes [ftp:@www-hgc.lbl.gov/pub/genesets] in human DNA, our gene
      finding system identified up to 85% of protein-coding bases correctly with a
      specificity of 80%. 58% of exons were exactly identified with a specificity of
      51%. Genie is shown to perform favorably compared with several other gene-finding
      systems.

PMID- 8877515
TI  - Parameterization studies for the SAM and HMMER methods of hidden Markov model
      generation.
AB  - Multiple sequence alignment of distantly related viral proteins remains a
      challenge to all currently available alignment methods. The hidden Markov model
      approach offers a new, flexible method for the generation of multiple sequence
      alignments. The results of studies attempting to infer appropriate parameter
      constraints for the generation of de novo HMMs for globin, kinase, aspartic acid
      protease, and ribonuclease H sequences by both the SAM and HMMER methods are
      described.

PMID- 8877516
TI  - Applications of GeneMark in multispecies environments.
AB  - This paper is supposed to bridge the gap between practical experience in using
      GeneMark for a rapidly widening repertoire of genomes, and the available
      publications that determine and compare the gene prediction accuracy of the
      GeneMark method for different genomes. Here we focus on the genome-specific
      variability of prediction error rates and their sources. DNA sequence
      inhomogeneity is present both in training and control sets of coding and non
      coding regions. Coding region inhomogeneity, caused by differences in sequence
      composition between "native" and horizontally transferred genes or between genes
      expressed at different levels, contributes to the false negative error rate.
      Inhomogeneity of non-coding region may frequently be caused by the presence of
      unnoticed genes and contributes to the false positive error rate. We have
      documented such unnoticed genes in GenBank sequences for several species Some of
      protein products of these genes have been characterized by similarity search
      methods. For others, which we call "pioneer genes", no significant similarity has
      been found at a protein sequence level although the confidence of GeneMark
      prediction is high. For instance, to date a majority of those pioneer gene
      predictions made for E. coli now show strong similarity to more recently
      characterized proteins that have been added to protein sequence database. Another
      practical question is related to genomic sequence inhomogeneity at interspecies
      level: if GeneMark has not been trained for a particular species, is it possible
      to apply models derived for phylogenetically close genomes? The answer is, yes.
      The results of cross-species gene prediction experiments show that cross-species
      prediction can often be reasonably accurate.

PMID- 8877517
TI  - Genome-scale DNA sequence recognition by hybridization to short oligomers.
AB  - Recently developed hybridization technology (Drmanac et al. 1994) enables
      economical large-scale detection of short oligomers within DNA fragments. The
      newly developed recognition method (Milosavljevic 1995b) enables comparison of
      lists of oligomers detected within DNA fragments against known DNA sequences. We
      here describe an experiment involving a set of 4,513 distinct genomic E.coli
      clones of average length 2kb, each hybridized with 636 randomly selected short
      oligomer probes. High hybridization signal with a particular probe was used as an
      indication of the presence of a complementary oligomer in the particular clone.
      For each clone, a list of oligomers with highest hybridization signals was
      compiled. The database consisting of 4,513 oligomer lists was then searched using
      known E.coli sequences as queries in an attempt to identify the clones that match
      the query sequence. Out of a total of 11 clones that were recognized at highest
      significance level by our method, 8 were single-pass sequenced from both ends.
      The single-pass sequenced ends were then compared against the query sequences.
      The sequence comparisons confirmed 7 out of the total of 8 examined recognitions.
      This experiment represents the first successful example of genome-scale sequence
      recognition based on hybridization data.

PMID- 8877518
TI  - Characterization of prokaryotic and eukaryotic promoters using hidden Markov
      models.
AB  - In this paper we utilize hidden Markov models (HMMs) and information theory to
      analyze prokaryotic and eukaryotic promoters. We perform this analysis with
      special emphasis on the fact that promoters are divided into a number of
      different classes, depending on which polymerase-associated factors that bind to
      them. We find that HMMs trained on such subclasses of Escherichia coli promoters
      (specifically, the so-called sigma 70 and sigma 54 classes) give an excellent
      classification of unknown promoters with respect to sigma-class. HMMs trained on
      eukaryotic sequences from human genes also model nicely all the essential well
      known signals, in addition to a potentially new signal upstream of the TATA-box.
      We furthermore employ a novel technique for automatically discovering different
      classes in the input data (the promoters) using a system of self-organizing
      parallel HMMs. These self-organizing HMMs have at the same time the ability to
      find clusters and the ability to model the sequential structure in the input
      data. This is highly relevant in situations where the variance in the data is
      high, as is the case for the subclass structure in for example promoter
      sequences.

PMID- 8877519
TI  - Refining neural network predictions for helical transmembrane proteins by dynamic
      programming.
AB  - For transmembrane proteins experimental determination of three-dimensional
      structure is problematic. However, membrane proteins have important impact for
      molecular biology in general, and for drug design in particular. Thus, prediction
      method are needed. Here we introduce a method that started from the output of the
      profile-based neural network system PHDhtm (Rost, et al. 1995). Instead of
      choosing the neural network output unit with maximal value as prediction, we
      implemented a dynamic programming-like refinement procedure that aimed at
      producing the best model for all transmembrane helices compatible with the neural
      network output. The refined prediction was used successfully to predict
      transmembrane topology based on an empirical rule for the charge difference
      between extra- and intra-cytoplasmic regions (positive-inside rule). Preliminary
      results suggest that the refinement was clearly superior to the initial neural
      network system; and that the method predicted all transmembrane helices correctly
      for more proteins than a previously applied empirical filter. The resulting
      accuracy in predicting topology was better than 80%. Although a more thorough
      evaluation of the method on a larger data set will be required, the results
      compared favourably with alternative methods. The results reflected the strength
      of the refinement procedure which was the successful incorporation of global
      information: whereas the residue preferences output by the neural network were
      derived from stretches of 17 adjacent residues, the refinement procedure involved
      constraints on the level of the entire protein.

PMID- 8877520
TI  - Finding genes in DNA using decision trees and dynamic programming.
AB  - This study demonstrates the use of decision tree classifiers as the basis for a
      general gene-finding system. The system uses a dynamic programming algorithm that
      finds the optimal segmentation of a DNA sequence into coding and non-coding
      regions (exons and introns). The optimality property is dependent on a separate
      scoring function that takes a subsequence and assigns to it a score reflecting
      the probability that the sequence is an exon. In this study, the scoring
      functions were sets of decision trees and rules that were combined to give the
      probability estimate. Experimental results on a newly collected database of human
      DNA sequences are encouraging, and some new observations about the structure of
      classifiers for the gene-finding problem have emerged from this study. We also
      provide descriptions of a new probability chain model that produces very accurate
      filters to find donor and acceptor sites.

PMID- 8877521
TI  - Compact encoding strategies for DNA sequence similarity search.
AB  - Determining whether two DNA sequences are similar is an essential component of
      DNA sequence analysis. Dynamic programming is the algorithm of choice if
      computational time is not the most important consideration. Heuristic search
      tools, such as BLAST, are computationally more efficient, but they may miss some
      of the sequence similarities (Altschul et al., 1990). These tools often use
      common k-tuples (words) between the two sequences to determine anchor points for
      the alignment, and spend most of their computational time extending the alignment
      beyond these anchor points. We discuss and provide a DNA sequence similarity
      search implementation (called SENSEI) that improves upon the performance of
      BLASTN by almost an order of magnitude for comparable sensitivity. This
      improvement is a result of using compactly encoded scoring tables for k-tuples,
      encoding bases with a single bit, filtering the sequence to remove the simple
      sequence repeats using XNUN, and masking the known species-specific repeats in
      the query sequence. To reduce memory requirements, especially for large genomic
      DNA query sequences, we recommend generating the neighborhood words from the
      target sequence at run-time, instead of generating them by preprocessing the
      query sequence.

PMID- 8877522
TI  - A knowledge-based method for protein structure refinement and prediction.
AB  - The native conformation of a protein, in a given environment, is determined
      entirely by the various interatomic interactions dictated by the amino acid
      sequence (1-3). We describe here a knowledge-based approach for protein structure
      assessment and prediction. Using a well-defined set of high-resolution protein
      structures, we have derived statistical potentials, in the form of atom-pairwise
      distance probability density functions. These provide a description of pairwise
      interatomic interactions of native proteins. When applied to highly randomized
      and noisy structures of proteins distinct from the basis set, native-like
      structures were obtained to very high precision (< or = 2A). The examples tested
      include proteins of all sizes (from 38 up to 461 amino acids long) and diverse
      topological structures (alpha, beta and alpha-beta classes). The potentials
      appear to be sensitive enough to recognize subtle distortions from a native
      packing structure and in optimization of structures drive them consistently to a
      higher probability. Therefore they provide a powerful tool for refinement of X
      ray and NMR derived structures at arbitrary degrees of initial precision.

PMID- 8877523
TI  - Discovering empirically conserved amino acid substitution groups in databases of
      protein families.
AB  - This paper introduces a method for identifying empirically conserved amino acid
      substitution groups. In contrast with existing approaches that view amino acid
      substitution as a pairwise phenomenon, the method presented here identifies
      conserved groups of amino acids using a data structure called a conditional
      distribution matrix. The conditional distribution matrix extends the concept of a
      pairwise substitution matrix by changing the context of substitution from a
      single amino acid to a group of amino acids. The matrix tabulates information
      from a database of protein families that contains numerous aligned positions.
      Each row in the matrix contains the distribution of amino acids in those aligned
      positions that contain a given conditioning group of amino acids. The method
      converts a database of protein families into a conditional distribution matrix
      and then examines each possible substitution group for evidence of conservation.
      The algorithm is applied to the BLOCKS and HSSP databases. Twenty amino acid
      substitution groups are found to be conserved empirically in both databases.
      These groups provide insight into biochemical properties that are conserved in
      protein evolution.

PMID- 8877524
TI  - Gene prediction by pattern recognition and homology search.
AB  - This paper presents an algorithm for combining pattern recognition-based exon
      prediction and database homology search in gene model construction. The goal is
      to use homologous genes or partial genes existing in the database as reference
      models while constructing (multiple) gene models from exon candidates predicted
      by pattern recognition methods. A unified framework for gene modeling is used for
      genes ranging from situations with strong homology to no homology in the
      database. To maximally use the homology information available, the algorithm
      applies homology on three levels: (1) exon candidate evaluation, (2) gene-segment
      construction with a reference model, and (3) (complete) gene modeling.
      Preliminary testing has been done on the algorithm. Test results show that (a)
      perfect gene modeling can be expected when the initial exon predictions are
      reasonably good and a strong homology exists in the database; (b) homology (not
      necessarily strong) in general helps improve the accuracy of gene modeling; (c)
      multiple gene modeling becomes feasible when homology exists in the database for
      the involved genes.

PMID- 8877525
TI  - Gene recognition in cyanobacterium genomic sequence data using the hidden Markov
      model.
AB  - We have developed a hidden Markov model (HMM) to detect the protein coding
      regions within one megabase contiguous sequence data, registered in a database
      called GenBank in eight entries, of the genome of cyanobacterium, Synechocystis
      sp. strain PCC6803. Detection of the coding regions in the database entry was
      performed by using HMM whose parameters were determined by taking the statistics
      from the rests of the entries. This HMM has states modeling the di-codons and
      their frequencies within coding regions and those modeling its base contents in
      the intergenic regions. Results of the cross-validation showed that the HMM
      recognized 92.1% of coding regions assigned in sequence annotation. In addition,
      it suggested 94 potential new coding regions whose length are longer than 90
      bases. The recognition accuracy calculated at the level of individual bases was
      90.7% for the coding regions and 88.1% for the intergenic regions. This
      corresponds to a correlation coefficient for coding region recognition of 0.784.
      Comparison with its prediction accuracy with that by GeneMark showed that the HMM
      has the same level of prediction accuracy as GeneMark on average. Since we can
      extend the HMM to utilize information such as SD sequences, the prediction
      accuracy of the HMM will be enhanced. It was observed that correlation was
      positive between the prediction rate of the coding regions and the G + C content
      at the third position of the codon. This suggests the possibility that the
      prediction rate of coding regions in the cyanobacteria sequence can be enhanced
      by improving the present HMM into that reflects the classification of coding
      regions based on the G + C content.

PMID- 8877526
TI  - Improving health care, Part 2: A clinical improvement worksheet and users'
      manual.
AB  - BACKGROUND: Small tests of change can be conducted in everyday clinical practice,
      thereby turning the health care delivery team into reflective practitioners who
      can learn from, and improve on, their work. CLINICAL IMPROVEMENT WORKSHEET AND
      USERS' MANUAL--CASE STUDY: The worksheet has been designed as a simple tool for
      applying clinical improvement to the core clinical delivery process. A carpal
      tunnel surgery (CTS) team was formed to improve outcomes and reduce costs for
      patients and to promote improvements in quality and value. The team wanted to
      determine if surgical patients treated with local anesthesia in an ambulatory
      setting have superior satisfaction with care, comparable clinical and functional
      outcomes, and lower medical (and social) costs. For the first time, standardized
      assessments of patient case mix, treatment processes, and health outcomes were
      designed into the delivery process by gathering data from the patient and from
      the surgeon presurgery and 4 weeks and 12 weeks postsurgery. Results for the
      first 49 of 50 to 100 consecutive patients show improved outcomes and reductions
      in costs, from $937 to $405 per patient. LESSONS LEARNED: Even though CTS was
      selected to be a quick and noncontroversial opportunity, considerable effort had
      to be expended to ensure that all clinicians and other affected staff would
      understand and support "the new way". RECOMMENDATIONS: "Ramp up" improvements as
      time passes, more and more change trials are conducted and their complexity
      increases. To ease implementation of changes, teams can diagram core process
      "components" and attach measures, use flowcharts to plan and monitor
      implementation and use change management thinking to help sharpen the plan and
      anticipate problems.

PMID- 8877527
TI  - From paper to practice to point of care: reports from a Zitter Group Conference
      on Implementing Practice Guidelines.

PMID- 8877528
TI  - Is downsizing affecting incident reports?

PMID- 8877529
TI  - [Bilateral femoral neuropathy after laparotomy].

PMID- 8877530
TI  - Anti-HIV therapy with antisense oligonucleotides and ribozymes: realistic
      approaches or expensive myths?

PMID- 8877531
TI  - Issues in the adjunct therapy of severe sepsis.
AB  - Until recently the concept of immunomodulation in patients with severe sepsis
      (formerly called sepsis syndrome or septic shock) appeared very promising.
      Research has focused on the possible therapeutic potential of interfering with
      cytokine pathways, either by preventing the induction of cytokines, such as TNF
      alpha, by neutralization of lipopolysaccharide (LPS), or through the use of
      agents that attenuate cytokine action. Nowadays research on protein or protein
      constructs with antibacterial activities such as bacterial/permeability
      increasing protein (BPI), platelet activating factor receptor antagonists, nitric
      oxide and cyclo-oxygenase inhibitors, are still being followed. In large clinical
      trials monoclonal antibodies against core glycolipid (E5, HAIA) were shown to be
      at best of only marginal benefit, and in some trials results were indecisive.
      Also, the results with IL-lra, although initially heralded with high expectation,
      were at the end disappointing and the trials discontinued. Two large trials with
      monoclonal antibodies against TNF showed some effect in subcategories of
      patients: a third trial is on its way. Other phase I; II studies include those of
      soluble TNF receptors and BPI. The area of immunomodulation has now become an
      area of more realism and the results of early trials has forced investigators to
      go back the drawing board and to re-investigate the whole concept of
      immunotherapy and immunoprophylaxis.

PMID- 8877532
TI  - Characterization of an inhibitor-resistant enzyme IRT-2 derived from TEM-2 beta
      lactamase produced by Proteus mirabilis strains.
AB  - Ten clinical isolates of Proteus mirabilis were found to produce an inhibitor
      resistant TEM beta-lactamase (IRT) in association with a TEM-1 enzyme. The IRT
      enzyme was derived from TEM-2. The blaIRT gene differs from blaTEM-2 gene by one
      point mutation which leads to the amino-acid substitution Arg-->Ser at position
      244, as observed for the original IRT-2 enzyme derived from TEM-1 reported in
      Escherichia coli. This is the first report of an IRT beta-lactamase derived from
      TEM-2.

PMID- 8877533
TI  - A new time-kill method of assessing the relative efficacy of antimicrobial agents
      alone and in combination developed using a representative beta-lactam,
      aminoglycoside and fluoroquinolone.
AB  - A time-kill curve employing nine sampling times over 6 h was used to provide data
      which were then used to develop a theoretical (best-fit) curve. From the
      theoretical curve parameters describing the rate of kill (alpha), time from
      addition of antibiotic to initiation of killing (d) and a function of the degree
      of killing observed (Ym/Yo) were defined. The area-under-the-curve (AUC) was
      calculated from the theoretical curve. The variability of each parameter was
      assessed using a theoretical curve to fit the data from experiments done on three
      occasions and in triplicate. In terms of the parameters alpha, d, Ym/Yo and AUC,
      no synergy was demonstrated with combinations of piperacillin/tazobactam plus
      ciprofloxacin or gentamicin when compared with single antibiotics. The AUC
      represents the best summary parameter of a time-kill curve but should be
      supported by other parameters describing the best-fit curve.

PMID- 8877534
TI  - CAT III chloramphenicol resistance in Pasteurella haemolytica and Pasteurella
      multocida isolated from calves.
AB  - Chloramphenicol, which had been used extensively for antimicrobial veterinary
      therapy, was prohibited in Europe in 1994. Soon after it became available,
      resistance to this drug was detected, generally conferred by plasmids encoding
      inactivating enzymes, the chloramphenicol acetyltransferases (CAT), in Gram
      negative as well as in Gram-positive bacteria. In the last few years, resistance
      to antibiotics emerged in Pasteurella strains from breeding herds and this
      evolution was followed by a national surveillance network. Chloramphenicol
      resistance was more recently detected in multiresistant strains. We studied 25
      strains of Pasteurella, selected for their resistance to chloramphenicol.
      Production of a CAT was demonstrated in all these strains. PCR amplification
      indicated that the CAT produced was of type III for 23 of them. In these strains,
      chloramphenicol-resistance was mediated by plasmids of about 5.1 kb. Southern
      blots on restriction fragments suggested a high degree of homology between these
      5.1 kb plasmids. In the two other strains, production of a CAT type I was
      demonstrated, and the corresponding genes were either shown on a plasmid of 17 or
      5.5 kb.

PMID- 8877535
TI  - Liposomal amphotericin B (AmBisome) reduces dissemination of infection as
      compared with amphotericin B deoxycholate (Fungizone) in a rate model of
      pulmonary aspergillosis.
AB  - The efficacy of AmBisome, a liposomal formulation of amphotericin B, was compared
      with that of Fungizone (amphotericin B desoxycholate), in a rat model of
      unilateral, pulmonary aspergillosis. Repeated administration of cyclophosphamide
      resulted in persistent, severe granulocytopenia. The left lung was inoculated
      with a conidial suspension of Aspergillus fumigatus, thus establishing an
      unilateral infection. Antifungal treatment was started 40 h after fungal
      inoculation, at which time mycelial disease was confirmed by histological
      examination. Both Fungizone 1 mg/kg and AmBisome 10 mg/kg resulted in increased
      survival in terms of delayed as well as reduced mortality. Quantitative cultures
      of lung tissue showed that only AmBisome 10 mg/kg resulted in reduction of the
      number of fungal cfus in the inoculated left lung. Compared with Fungizone, both
      AmBisome 1 mg/kg/day and AmBisome 10 mg/kg/day significantly prevented
      dissemination from the infected left lung to the right lung. In addition, both
      AmBisome regimens reduced hepatosplenic dissemination, and the 10 m/kg dosage
      fully prevented this complication. In conclusion, when compared with Fungizone,
      in this model AmBisome is more effective in reducing dissemination of unilateral,
      pulmonary aspergillosis, even when given in relatively low dosage. Such low
      dosages may have a place in prophylactic settings.

PMID- 8877536
TI  - Correlation of in-vitro activity and pharmacokinetic parameters with in-vivo
      effect of amoxycillin, co-amoxiclav and cefotaxime in a murine model of
      pneumococcal pneumonia.
AB  - In an attempt to determine the susceptibility breakpoints for amoxycillin, co
      amoxiclav and cefotaxime in pneumococcal pneumonia, a neutropenic mouse model was
      established and tested with two strains having different susceptibility to
      penicillins and cefotaxime. With a penicillin-sensitive strain (MIC/MBC =
      0.01/0.01 mg/L) the minimum dosage tested achieving significant cure was 2 mg/kg
      for amoxycillin, co-amoxiclav and cefotaxime. For the penicillin-insensitive
      strain (MIC/MBC = 1/2 mg/L), the minimum dosage tested giving significant cure
      was 50 mg/kg for amoxycillin and co-amoxiclav but 100 mg/kg for cefotaxime. Our
      results support the belief that MICs of amoxycillin, co-amoxiclav and cefotaxime
      for pneumococcal strains of < or = 0.5 or < or = 1 mg/L can be considered as
      clinically relevant susceptibility breakpoints.

PMID- 8877537
TI  - Pefloxacin penetration into human necrotic pancreatic tissue.
AB  - Antibiotic prophylaxis may be useful in acute necrotising pancreatis, a disease
      associated with a considerable incidence of infectious complications. The aim of
      this study was to assess pefloxacin penetration into necrotic pancreatic tissue
      during human necrotic pancreatitis. Ten patients (mean age 53.2 +/- 17.4 years)
      with severe acute pancreatitis (mean Ranson score 4.3) were studied. Pefloxacin
      was administered at a dose of 400 mg bd every 12 h by i.v. infusion (bolus, 15
      min). Intraoperative samples of necrotic pancreatic tissue and blood were
      collected simultaneously 1, 2, 4.5, 6, 8.5 or 10 h after the last pefloxacin
      administration in patients treated for 1, 3, 4, 7, 8, 17 or 20 days. Drug
      concentrations were determined by the microbiological agar-well diffusion method
      (Escherichia coli Kp 05124 as test micro-organism in Isosensitest Agar). Levels
      in serum ranged from 2.0 to 9.0 mg/L (at 2 and 6 h, respectively), in necrotic
      pancreatic tissue from 2.0 to 29.0 micrograms/g depending on different sampling
      time. Maximum tissue peak concentrations appeared between 4 and 6 h. The necrotic
      pancreatic tissue/serum concentration ratio ranged from 0.9 to 5.1, values
      depending on tissue sample collection. Therapeutic concentrations (20.6
      micrograms/g) above the MIC of potentially pathogenic enteric microorganisms were
      still present in necrotic pancreatic tissue 10 h after the last drug
      administration. Pefloxacin appeared to concentrate in necrotic pancreatic tissue,
      without appreciable accumulation after multiple-dose administration. The
      pefloxacin concentrations in necrotic pancreatic tissue showed high variability,
      depending on the degree of necrosis, inflammation and sample vascularization. Our
      results provided evidence of good, prompt penetration of pefloxacin into necrotic
      pancreatic tissue. Pefloxacin seems to exhibit favourable pharmacokinetic and
      pharmacodynamic properties for pancreatic infections.

PMID- 8877538
TI  - Imipenem resistance among Acinetobacter baumannii: association with reduced
      expression of a 33-36 kDa outer membrane protein.
AB  - The mechanism of imipenem resistance of two Acinetobacter baumannii isolates (A-1
      and A-24) was characterized in this study. A spontaneous revertant (A-1 (rev))
      derived from isolate A-1 showed susceptibility to imipenem. beta-Lactamase
      hydrolysis studies showed no evidence of an imipenem hydrolyzing enzyme among A
      1, A-24, A-1 (rev), or two other imipenem susceptible A. baumannii isolates.
      Outer membrane protein (OMP) analysis indicated decreased expression of a 33-36
      kDa protein by isolates A-1 and A-24 when compared with A-1 (rev) and the other
      A. baumannii isolates. In conclusion, decreased expression of a 33-36 kDa OMP is
      associated with imipenem resistance among A. baumannii.

PMID- 8877539
TI  - Aerococcus-like organisms: use of antibiograms for diagnostic and taxonomic
      purposes.
AB  - Recently, some Aerococcus-like organisms (ALOs), isolated from urine and blood of
      elderly patients with urinary tract infection, have been described. In this study
      ALOs and related taxons were tested for susceptibility by agar diffusion and agar
      dilution methods to 15 selected antimicrobial agents for diagnostic and taxonomic
      considerations. ALOs were susceptible to a wide range of antimicrobials including
      beta-lactams, but resistant to aminoglycosides, sulphonamides, trimethoprim and
      nalidixic acid. By using tablets containing vancomycin, furazolidone and
      bacitracin, it was possible to separate ALOs from related taxons. Clustering
      based on antibiotic susceptibilities showed that there is little similarity
      between Aerococcus viridans and ALOs.

PMID- 8877540
TI  - In-vitro activity of ofloxacin, levofloxacin and D-ofloxacin against
      staphylococci.
AB  - The in-vitro activity of levofloxacin was compared with ofloxacin and D-ofloxacin
      against 130 isolates of Staphylococcus aureaus and 117 isolates of coagulase
      negative staphylococci, using the agar dilution method. In general, levofloxacin
      was equally active or up to fourfold more active than ofloxacin against all
      staphylococci, including 61 methicillin-resistant S. aureus. In contrast, D
      ofloxacin showed little activity against all isolates tested.

PMID- 8877541
TI  - In-vitro activity of ramoplanin (a novel lipoglycopeptide), vancomycin, and
      teicoplanin against gram-positive clinical isolates from cancer patients.
AB  - The in-vitro activities of ramoplanin, vancomycin, and teicoplanin against Gram
      positive organisms isolated from cancer patients were determined. Ramoplanin was
      the most active agent tested inhibiting all isolates at a concentration of < or =
      0.5 mg/L. Although all isolates were also susceptible to vancomycin and
      teicoplanin, their activities were surpassed by that of ramoplanin. The activity
      of teicoplanin was moderately better than that of vancomycin against Bacillus
      cereus, Enterococcus faecium, Listeria monocytogenes, methicillin-resistant
      Staphylococcus aureus, and most streptococcal isolates, and was comparable to
      vancomycin for the remainder of the isolates tested.

PMID- 8877542
TI  - The in-vitro activity of trovafloxacin and nine other antimicrobials against 413
      anaerobic bacteria.
AB  - The in-vitro activity of trovafloxacin and nine other antimicrobials was
      determined for 413 non copy anaerobic clinical isolates. Trovafloxacin was the
      most active quinolone tested with an MIC90 of 0.5 mg/L against Gram-positive
      cocci (n = 75); MIC90 of 4 mg/L against Gram-positive bacilli (n = 151); MIC90 of
      0.5 mg/L for Gram-negative cocci (n = 12) and MIC90 of 1 mg/L for Gram-negative
      bacilli (n = 175). Overall the MIC90 of trovafloxacin was 1 mg/L which was
      equivalent to co-amoxiclav and one dilution higher than that of imipenem. The
      other seven comparators, including clindamycin and metronidazole, had higher
      MIC90 values than trovafloxacin. Trovafloxacin is likely to have clinically
      useful activity against anaerobes from human infection.

PMID- 8877543
TI  - Antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in
      Lebanon.
AB  - A total of 61 clinical isolates of Streptococcus pneumoniae from Lebanon were
      tested for their susceptibility to penicillin G and seven other antibiotics by
      the agar dilution technique. All penicillin-susceptible isolates were also
      susceptible to chloramphenicol, ceftriaxone and erythromycin. Penicillin
      resistant isolates were consistently susceptible only to erythromycin.

PMID- 8877544
TI  - In-vitro interactions of DX-8739, a new carbapenem, meropenem and imipenem with
      amikacin against multiresistant Pseudomonas aeruginosa.
AB  - In order to investigate the antimicrobial interactions against multiresistant
      Pseudomonas aeruginosa, thirty-seven strains resistant to antimicrobial agents of
      five different chemical classes were exposed in vitro to the combination of three
      carbapenems. DX-8739, a novel DHP-I stable analogue, meropenem and imipenem with
      amikacin. The tested combinations expressed an enhanced killing activity against
      38-46% of strains and an additive effect against 5-13%. These effects were the
      same whether the applied carbapenem was DX-8739, meropenem or imipenem; they were
      also independent of the MIC of any antimicrobial.

PMID- 8877545
TI  - Effect of replacing cefotaxime with ceftizoxime in a hospital where penicillin
      resistant pneumococcal disease is prevalent.
AB  - Ceftizoxime and cefotaxime demonstrate very similar activities in vitro against a
      broad range of bacteria. To reduce costs, our hospital pharmacy implemented an
      automatic substitution policy whereby ceftizoxime was dispensed and administered
      whenever cefotaxime was ordered. This policy was modified when penicillin
      resistant Streptococcus pneumoniae isolates were found to be markedly less
      susceptible to ceftizoxime than to cefotaxime, of concern considering the
      prevalence and virulence of this pathogen. We compared clinical findings among
      179 adult patients treated with ceftizoxime for any indication during the
      substitution months with 200 patients treated with cefotaxime during the previous
      year. The ceftizoxime group had a shorter mean length of stay, which paralleled a
      hospital-wide trend toward more efficient discharge planning. After adjusting for
      this trend, we observed no significant difference in duration of study drug,
      number of other intravenous antibiotics, likelihood of receiving additional
      antibiotics after study drug completion, or patient survival. Fortuitously, no
      penicillin-resistant pneumococcal infections were documented in ceftizoxime
      treated patients. This study suggests that cefotaxime and ceftizoxime are
      comparable. The choice of one versus the other may be dictated by price, provided
      ceftizoxime is not used for proven or suspected penicillin-resistant pneumococcal
      infections.

PMID- 8877546
TI  - Optimizing the timing of antimicrobial prophylaxis in surgery: an intervention
      study.
AB  - The timing of surgical antimicrobial prophylaxis was determined before and after
      an intervention programme of education of surgeons, anaesthetists and nurses on
      the subject of antimicrobial drug prophylaxis, and the subsequent implementation
      of new protocols of single dose prophylaxis administered within one hour before
      incision. This prospective study was performed in three surgical departments of a
      university hospital. For comparison, the timing of prophylaxis was also
      determined in an operating department of a community hospital. The timing
      improved considerably in the departments of the university hospital where the
      intervention was carried out: administration of the first dose within one hour
      before incision increased from 39% to 69% in department A and from 64% to 80% in
      department B. Before the intervention, seven out of 16 prophylactic doses were
      given after inflation of the tourniquet. After the intervention all doses of
      prophylactic antibiotics were administered before inflation of the tourniquet.
      Initially, the intervals of multidose prophylaxis varied widely. In the second
      review, single-dose prophylaxis increased from 21% to 78% in department A and
      from 31% to 85% in department B. We conclude that the intervention succeeded in
      improving the quality of surgical prophylaxis.

PMID- 8877547
TI  - The influence of the opinion of an infectious disease consultant on the
      appropriateness of antibiotic treatment in a general hospital.
AB  - The antibiotics chosen in hospitals are not always the most appropriate. A
      comparative prospective study with sequential analysis was designed to assess how
      the opinion of an infectious disease consultant affected the clinical efficacy of
      antimicrobial treatment in a general hospital. We studied 250 patients who had
      microbiologically documented infections according to Center for Disease Control
      criteria. The patients were divided in two groups with similar initial
      characteristics. Group G1 comprised 100 patients without infectious disease
      consultation, and group G2 contained 150 patients with infectious disease
      consultation. The influence of the consultant's opinion was assessed as the
      percentage of initially appropriate treatments, and by the number of
      inappropriate ones that were changed after the microbiological results were
      known. The appropriateness of initial treatment was significantly higher in group
      G2 (66% vs 55%), as were the number of treatments changed on the basis of the
      microbiological results (57.6% vs 33.3%). This lead to higher rates of cure,
      fewer deaths, and fewer cases of persistent infection in group G2. In 42.4% of G2
      patients, antibiotic treatment was not changed in spite of the microbiological
      results and the opinion of an infectious disease consultant. We conclude that
      antibiotic treatment for the most clinically significant infections can be
      optimized if it is dispensed according to carefully developed guidelines.

PMID- 8877548
TI  - Quinolone resistance and Campylobacter species.

PMID- 8877549
TI  - Susceptibility of staphylococci to teicoplanin and vancomycin.

PMID- 8877550
TI  - Cefuroxime disc susceptibility test criteria for Streptococcus pneumoniae.

PMID- 8877551
TI  - In-vitro activities of clarithromycin and other antimicrobial agents against
      Helicobacter pylori isolated from children.

PMID- 8877552
TI  - The activity of cefetamet against enterobacterial isolates from community
      acquired urinary tract infections.

PMID- 8877553
TI  - Sensitivities to four carbapenems of bacteria isolated from patients with
      refractory complicated urinary tract infections and the detection of
      carbapenemase-producing Pseudomonas aeruginosa.

PMID- 8877554
TI  - In-vitro selection of quinolone-resistant staphylococcal mutants by a single
      exposure to ciprofloxacin or trovafloxacin (CP-99,219) -letter-.

PMID- 8877555
TI  - Once-a-day carbapenem therapy.

PMID- 8877556
TI  - Solution structure of a cyclic RGD peptide that inhibits platelet aggregation.
AB  - Peptides containing the Arg-Gly-Asp (RGD) sequence can inhibit platelet
      aggregation. Incorporation of this sequence into a cyclic peptide results in
      specific binding to a particular integrin. Studies of cyclic RGD peptides show
      that residues surrounding the RGD sequence have important effects on the
      selectivity of the peptide to bind with glycoprotein IIb/IIIa (GPIIb/IIIa). In
      this paper, we elucidate the conformation of cyclo(2,10)Ac-Gly1-Pen2-Gly3-His4
      Arg5-Gly6-Asp7 -Leu8-Arg9-Cys10-Ala11-NH2 (1) by NMR and molecular dynamics
      simulations. This peptide inhibits platelet aggregation in a manner similar to
      that reported for cyclo(2,10)Gly1-Pen2-Gly3-His4-Arg5-Gly6-Asp7-Le u8-Arg9-Cys10
      Ala11-OH (6) (Cheng, S. et al. J. Med. Chem. 1994, 37, 1-8), which is shown to be
      selective for the GPIIb/IIIa receptor. The cyclic peptide 1 exhibited a major and
      a minor conformer in solution. In the major conformer, the His4-Arg5-Gly6-Asp7
      segment encompasses a 4-->1 hydrogen bond with a distorted type II beta-turn, and
      the minor conformer has turn-extended-turn. A comparison between the major
      conformation of this peptide and those of other cyclic RGD peptides suggests the
      importance of a hydrophobic residue adjacent to the RGD sequence.

PMID- 8877557
TI  - The interaction between the novel intercalator diethidium cation and B-form DNA:
      a theoretical study.
AB  - This research is an effort to further understand the physicochemical interaction
      between the novel drug molecule diethidium (2,7-diamino 9-[2,7 diamino 10-nN
      phenanthridium] 10-nN-phenanthridium) and its biological receptor DNA. The
      ultimate goal is the elucidation of this novel class of drugs as potential
      pharmaceutical agents. Understanding the physicochemical properties of this drug
      as well as the mechanism by which it interacts with DNA should ultimately allow
      the rational design of novel anti-cancer or anti-viral drugs. A novel binding
      structure for the diethidium cation to B-form DNA is herein described. Molecular
      modeling on the complex formed between diethidium and a dodecamer of double
      stranded B-form DNA, CGCGAATTCGCG, has shown that this complex is indeed fully
      capable of participating in the formation of a stable intercalation site. It was
      expected that diethidium would have a mechanism of intercalation significantly
      different from other classical intercalators because a) Its structure, that of
      two perpendicular planes, each known to have excellent intercalation properties,
      is novel b) The linker region length is zero c) The tilt between the two planes
      of the drug matches the geometry of the space available to this drug in the major
      groove. We have studied the complex formed when diethidium enters the central
      site of the B-DNA dodecamer through the major groove. The complex forms several
      classes of intercalation structures, which are all stable and vary from
      "partially intercalated" to "fully intercalated". Multiple minimizations show the
      drug to be very mobile within the intercalation site. Further, some structures
      show organization and concomitant stiffening of the DNA above the intercalation
      site, with a disorganization and disruption of the regular B-DNA structure
      immediately below the intercalation site. This particular phenomena may be
      expected to lead to significantly different physicochemical properties for the
      diethidium complex with respect to other known intercalators, because this sort
      of vectorial difference in structure above and below the site of intercalation is
      unknown in existing intercalators, as far as the authors are aware. In addition,
      we expect the mechanism of interaction between drug and DNA to be described by
      "direct ligand transfer", wherein the drug is transferred from duplex DNA to
      duplex DNA without re-entering the solvent. This work is the first instance known
      to the authors of a novel drug entity that was deduced solely by mathematical
      reasoning and described subsequently by computational methods. Evidence that
      diethidium should interact with its target site DNA differently from other known
      intercalators is strong.

PMID- 8877558
TI  - The design of an inhibitor using alpha, beta-dehydro residues.
AB  - X-ray crystallography and NMR spectroscopic studies on peptides containing alpha,
      beta-unsaturated (dehydro) residues have indicated that the steric effects caused
      by the dehydro residue are strong and predictable, and such residues can be used
      to generate specific peptide structures. In particular, dehydro-Alanine (delta
      Ala) is found to adopt an extended conformation and also induces a definite
      conformation in the neighboring saturated residue. In order to design a sequence
      that would fold into a known three-dimensional structure, we have undertaken a
      systematic theoretical study of the preferred conformations of tetrapeptide
      sequences of the type N-Ac-delta Ala-X-delta Ala-NHCH3 (x = Gly, L-Ala, L-Val, L
      Leu, L-Lys, L-Arg, L-Phe). The methodology and parameters used have been
      standardized against sequences with known crystal structures. In all the
      sequences a consistent folding pattern is observed in which the delta Ala
      residues are in an extended conformation with phi approximately 140 degrees and
      psi approximately -40 degrees. The results are used to predict a sequence which
      has a structure very similar to that of the binding loop region of the bovine
      pancreatic trypsin inhibitor (BPTI).

PMID- 8877559
TI  - Tryptophan intercalation in G, C containing polynucleotides: Z to B conversion of
      poly [d(G-5M C)] in low salt induced by a tetra peptide.
AB  - Binding of a tetra peptide, lysyl tryptophenyl glycyl lysine O-ter butyl ester
      (KWGK) with duplex forms of G, C containing polynucleotides, Poly [d(G-C)], Poly
      [d(G-5M C)], Poly (dG), Poly (dC) and E.coli DNA were studied under low salt
      conditions using UV absorption, fluorescence, and circular dichroic (C.D)
      spectroscopy. On addition of the peptide (upto a P/N mole ratio of 0.5), the Poly
      [d(G-5M C)] under low salt (1 mM Na Cl) conditions, was converted from Z to B
      form as shown by the inversion of C.D spectra. The two binding constants (K1 and
      K2) were determined from fluorescence spectroscopy of which K2 estimates the
      intercalation of the tryptophenyl side chain between the base pairs of DNA and K1
      estimates the electrostatic interactions between the lysyl side chains and
      phosphate groups. The strength of intercalation is: Z-form of Poly [d(G-5M C)] >>
      B form of Poly [d(G-5M C)] >> E.Coli DNA > Poly (dG).Poly (dC). This means that
      peptide seems to have strong preference for Z compared to B-form and for
      alternating over non-alternating G, C Sequences. This suggests that tryptophan
      intercalation may act as a discriminating factor in recognizing Z and B-forms and
      may have a potential role in Protein-Nucleic acid interactions that are important
      for transcription.

PMID- 8877560
TI  - Design of sequence-specific DNA binding ligands that use a two-stranded peptide
      motif for DNA sequence recognition.
AB  - The design and DNA binding activity of beta-structure-forming peptides and
      netropsin-peptide conjugates are reported. It is found that a pair of peptides
      S,S'-bis(Lys-Gly-Val-Cys-Val-NH-NH-Dns)-bridged by an S-S bond binds at least 10
      times more strongly to poly(dG).poly(dC) than to poly(dA).poly(dT). This peptide
      can also discriminate between 5'-GpG-3' and 5'-GpC-3' steps in the DNA minor
      groove. Based on these observations, new synthetic ligands, bis-netropsins, were
      constructed in which two netropsin-like fragments were attached by means of short
      linkers to a pair of peptides-Gly-Cys-Gly- or Val-Cys-Val-bridged by S-S bonds.
      These compounds possess a composite binding specificity: the peptide chains
      recognize 5'-GpG-3' steps on DNA, whereas the netropsin-like fragments bind
      preferentially to runs of 4 AT base pairs. Our data indicate that combining the
      AT-base-pair specific properties of the netropsin-type structure with the 5'-GpG
      3'-specific properties of certain oligopeptides offers a new approach to the
      synthesis of ligands capable of recognizing mixed sequences of AT- and GC-base
      pairs in the DNA minor groove. These compounds are potential models for DNA
      binding domains in proteins which specifically recognize base pair sequences in
      the minor groove of DNA.

PMID- 8877561
TI  - Crystal structure of d(AGGBrCATGCCT): implications for cobalt hexammine binding
      to DNA.
AB  - The crystal structure of the DNA decamer d(AGGBrCATGCCT) has been determined to a
      resolution of 2.0 A and R factor of 19.6%. Crystals of d(AGGBrCATGCCT) were grown
      in the presence of cobalt hexammine but no cobalt hexammine ions are bound to the
      DNA structure. This contrasts with the recently determined crystal structure of
      d(AGGCATGCCT) which has a similar DNA conformation and cobalt hexammine ions
      bound directly to the DNA. Comparison with the structure of d(AGGCATGCCT) and
      appreciation of the crystal packing of this sequence leads to an understanding of
      how cobalt hexammine binding to DNA occurs and its role in determining DNA
      conformation.

PMID- 8877562
TI  - UV light-induced crosslinking of short DNA duplex strands: nucleotide sequence
      preferences and a prominent role of the duplex ends.
AB  - By various doses of UV light, we irradiated 32 short DNA duplexes having between
      12 and 40 nucleotide residues in length, and monitored the induced crosslinks
      between the complementary DNA strands by denaturing polyacrylamide gel
      electrophoresis. The experiments revealed that the crosslinking was strongest
      with the alternating sequence of T and A and weaker with the alternating sequence
      of T and G (C and A in the complementary strand). On the other hand, GC blocks of
      any sequence provided undetectable amounts of interstrand crosslinks even at the
      highest doses of UV irradiation. The amount of crosslinked strands
      logarithmically increased with the UV dose but it did not depend on the
      oligonucleotide concentration, ionic strength, divalent magnesium or manganese
      cations and pH at least within the examined regions of the experimental
      conditions, unless the oligonucleotide denatured or isomerized into a
      unimolecular foldback. The extent of crosslinking also did not depend on the (dT
      dA)n duplex length to indicate that the crosslink was predominantly localized at
      a specific duplex locus. Experiments with (dT-dA)8 "mutants" in which AT pairs
      were systematically replaced by GC pairs at various molecule positions, revealed
      that the crosslinking predominantly occurred at the oligo(dT-dA) duplex ends. The
      crosslinking is a direct method to detect duplexes of DNA, which is here, for
      example, demonstrated with the heteroduplex of (dT-dA)12 and (dT-dA)16.

PMID- 8877563
TI  - NMR solution structure of a DNA decamer containing an interstrand cross-link of
      the antitumor drug cis-diamminedichloroplatinum (II).
AB  - A 10 base pairs double-stranded oligonucleotide with the sequence d(CCTCG.CTCTC).
      d(GAGAG.CGAGG) containing a single interstrand cross-link resulting from
      chelation of the N7 position of two guanine residues on the opposite strands of
      DNA at the d(G.C/G.C) site by a cis-diammineplatinum(II) residue was analyzed by
      1H NMR spectroscopy. All the exchangeable and nonexchangeable protons resonance
      lines (except some H5'-H5") were assigned. NOESY spectra and chemical shifts
      indicated that the cross-linkage of the guanines of G.5 and G.6 induced
      extrahelicity of C5 and C6. Moreover, several unusual proximities were observed
      such as: (i) NOE cross-peaks between the H2'-H2" of G.5 or G.6 and the aromatic
      proton of their 5' neighbor C4 or A7 (ii) the absence of cross-peak for the steps
      G.5-C6, C6-T7 and C5-G4 (iii) a strong NOESY connectivity between H8(G.5) and
      H2(A7). All these data allowed us to describe the head to tail arrangement of the
      two cross-linked guanines as well as their stacking with flanking neighbor
      nucleotides (G.5 with T7.A7 base pair and G.6 with C4.G4 base pair). Using all
      the NOESY and TOCSY data (208 constraints), we have obtained a solution structure
      of the cross-linked duplex by using the NMR-constrained molecular mechanics
      program JUMNA. The reversal position of the two cross-linked guanines placed the
      cis-diammineplatinum(II) residue in the minor groove. The stacking of the two
      cross-linked guanines with the surrounding bases induced a bend of 40 degrees
      toward the minor groove. The locally left-helix formation, the extrusion of the
      cytosines and the stacking of the platinated guanines led to an unwinding of 76
      degrees. This value is in good agreement with the values deduced from gel
      electrophoresis experiments.

PMID- 8877564
TI  - Single stand targeted triplex formation: physicochemical and biochemical
      properties of foldback triplexes.
AB  - Oligodeoxyribonucleotides containing both Watson-Crick and Hoogsteen hydrogen
      bonding domains joined by a nucleotide loop (FTFOs) are studied for their binding
      affinity and specificity to the DNA and RNA single-stranded targets. Thermal
      denaturation studies reveal that FTFOs have high binding affinity for their
      targets than do antisense (duplex forming) and antigene (triplex forming)
      oligonucleotides, because of involvement of both the Watson-Crick and Hoogsteen
      domains in the interaction. Studies with FTFOs containing different sizes and
      sequences of loops show that 4-6 bases long loops are optimum for binding; loop
      sequence does not have a dramatic effect on binding. The FTFOs have greater
      sequence specificity than do antisense and antigene oligonucleotides because they
      read the target sequence twice. SI-, PI- and mung bean nuclease protection assays
      show that the DNA FTFO forms a stable triplex with the DNA target strand, but a
      weak or no triplex with the RNA target strand. Gel mobility shift assay is used
      to determine binding of FTFOs to DNA and RNA targets. The circular dichroism (CD)
      spectrum of the foldback triplex formed with the DNA target strand resembles the
      B-DNA spectrum, suggesting that the triplex has a B-type of conformation.

PMID- 8877565
TI  - A resonance Raman spectroscopic study of the quadruplex form of polyriboinosinic
      acid.
AB  - The four stranded form of polyriboinosinic acid, or poly(rl), formed under
      conditions of high ionic strength, has been studied principally by resonance
      Raman spectroscopy excited in the ultraviolet absorbent band of the hypoxanthine
      residues. UV Absorption and circular dichroism studies were made, principally in
      order to verify the presence of the quadruplex form at the low concentrations of
      poly(rl) used, and a trial experiment with the structural probe Tb3+ was also
      performed. Experimental evidence is found for highly stacked metastable forms
      present at low concentrations of polynucleotide, which are destroyed by heating
      in favor of the two well known forms.

PMID- 8877566
TI  - Sodium and potassium ion-promoted formation of supramolecular aggregates of 2'
      deoxyguanylyl-(3'-5')-2'-deoxyguanosine.
AB  - Guanine mono-, oligo-, and polynucleotides, including the guanine-rich telomeric
      sequences found at the ends of chromosomes, have been shown to form self
      associated species which contain cyclic tetramers of hydrogen-bonded guanines (G
      tetrads). In this study the effect of the tetramethylammonium (TMA+), Na+, and K+
      ions on the self-aggregation of 2'-deoxyguanylyl-(3'-5')-2'-deoxyguanosine,
      d(GpG), in aqueous solution has been studied by 1H NMR and FTIR spectroscopy.
      Although just a dinucleotide, it was found that d(GpG) self-associates to form
      extremely large assemblies in the presence of Na+ or K+ ions, especially the
      latter. The observed cation order for self-aggregation is TMA+ << Na+ < K+, with
      TMA+ having only a weak effect. Assuming a two-state model, the Tm for Na[d(GpG)]
      is 22 degrees C and for K[d(GpG)] is 42 degrees C, as determined by 1H NMR. Below
      the melting temperatures a large loss in intensity of the NMR signals was
      observed for these two salts, indicating that very large aggregates are forming
      in aqueous solution at pD 8. The intensity loss has been estimated to be 85% at 2
      degrees C for Na[d(GpG)] and 88% at 24 degrees C for K[d(GpG)]; there is no
      observable signal for K[d(GpG)] at 2 degrees C. Incremental addition of KCI to 8
      mM Na[d(GpG)] shows that at a mole ratio of d(GpG):KCI of 1:1 at 25 degrees C the
      total intensity loss is 98%. The presence of additional salt, especially a K
      salt, increases the formation of the supramolecular aggregates. 1H NMR of 9 mM
      Na[d(GpG)] in 90% H2O/10% D2O at 7 degrees C suggest that there are at least tow
      different species present, one of which has a G-tetrad structure, or that there
      are two different environments for the N1H in the G-tetrads. NOESY spectra of
      Na[d(GpG)] suggest that the glycosidic confomation is anti for both bases and
      that the dinucleotide units are stacking in a parallel fashion. Variable
      temperature FTIR spectroscopy in the 1750-1500 cm-1 region corroborates the
      cation-effect order found by NMR and shows that base-stacking and base-base
      hydrogen bonding are occurring in the aggregated species.

PMID- 8877567
TI  - Stereochemical assignment of chiral phosphotriester analogues with Alu I sites.
AB  - The stereochemistry of the diastereomers of a DNA duplex with the 2,2,2-trichloro
      1,1,-dimethylethyl (TCDME) phosphotriester backbone substitution has been
      assigned by the use of 2D NMR spectroscopy. The duplex
      [G1G2A3A4G5p(TCDME)C6T7A8G9G10]-[C11C12T13A14G15C16 T17T18C19C20] is a substrate
      of the restriction endonuclease Alu I, with placement of the TCDME group at the
      G5-C6 cleavage site of one strand. The stereochemical orientation of the TCDME
      group in relation to the structure of the double helix regulates the ability of
      Alu I to hydrolyze the complementary recognition site. The phosphotriester group
      of the isomer 1 duplex blocks cleavage of the complementary strand, while that of
      the isomer 2 duplex allows cleavage to proceed. Within the phosphotriester
      recognition site, no hydrolysis is detected nor is any seen when the single
      stranded DNA substrate is utilized. Data from the 2D NOESY spectra demonstrate
      that both DNA duplexes retain basic B-form geometry. The isomer 1 duplex shows
      NOE cross-relaxation from the protons of the two methyl groups of the TCDME
      modification (1.99, 2.00 ppm) to the G5 H3'(5.30 ppm), G5 H4' (4.53 ppm), and C6
      H5'/H5" (4.52, 4.62 ppm) protons. The isomer 2 duplex shows NOE cross-relaxation
      from the methyl protons of the TCDME modification (2.01, 2.03 ppm) to the C6 H6
      (7.15 ppm), C6 H4' (4.30 ppm), C6 H5'/H5" (4.48, 4.62 ppm), G5 H3' (5.26 ppm),
      and G5 H4' (4.48 ppm) protons. Thus the NOE cross-relaxation between the methyl
      protons of the TCDME modification and the C6 H6 and C6 H4' protons in isomer 2 is
      not found in the spectra of the isomer 1 duplex. These NMR data confirm the
      stereochemical assignment of the chirality of the TCDME phosphotriester group in
      isomer 1 as the Sp configuration and in isomer 2 as the Rp configuration. The Sp
      isomer features the TCDME group pointing away from the helix, while the Rp isomer
      shows the TCDME group pointing towards the major groove. Thus through the use of
      2D NMR techniques, the stereochemistry of chiral phosphotriester linkages may be
      assigned in chemically modified DNA.

PMID- 8877568
TI  - Hydrogen bonding and stacking of DNA bases: a review of quantum-chemical ab
      initio studies.
AB  - Ab initio quantum-chemical calulations with inclusion of electron correlation
      made since 1994 (such reliable calculations were not feasible before)
      significantly modified our view on interactions of nucleic acid bases. These
      calculations allowed to perform the first reliable comparison of the strength of
      stacked and hydrogen bonded pairs of nucleic acid bases, and to characterize the
      nature of the base-base interactions. Although hydrogen-bonded complexes of
      nucleobases are primarily stabilized by the electrostatic interaction, the
      dispersion attraction is also important. The stacked pairs are stabilized by
      dispersion attraction, however, the mutual orientation of stacked bases is
      determined rather by the electrostatic energy. Some popular theories of stacking
      were ruled out: The theory based on attractive interactions of polar exocyclic
      groups of bases with delocalized electrons of the aromatic rings (Bugg et al.,
      Biopolymers 10, 175 (1971), and the pi-pi interactions model (C.A. Hunter, J.
      Mol. Biol. 230, 1025 (1993)). The calculations demonstrated that amino groups of
      nucleobases are very flexible and intrinsically nonplanar, allowing hydrogen-bond
      like interactions which are oriented out of the plane of the nucleobase. Many H
      bonded DNA base pairs are intrinsically nonplanar. Higher-level ab initio
      calculations provide a unique set of reliable and consistent data for
      parametrization and verification of empirical potentials. In this article, we
      present a short survey of the recent calculations, and discuss their significance
      and limitations. This summary is written for readers which are not experts in
      computational quantum chemistry.

PMID- 8877569
TI  - CICADA interface with AMBER. An application on oligonucleotides and their
      fragments.
AB  - The potential energy hypersurfaces (PES) of several nucleotide fragments were
      analyzed by the conformational search algorithm CICADA interfaced with the
      molecular mechanics program AMBER, version 4.0. The low energy conformers for
      dimethylphosphate, dinucleoside monophosphate fragments, and deoxyadenosine are
      described. Calculated relative and absolute flexibilities of single conformers,
      molecular fragments as well as entire molecules are introduced. The comparison of
      the results with the literature data shows good ability of the CICADA-AMBER
      combination to describe conformational space. It is revealed that the number of
      low energy conformers as well as flexibility decreases as the size of the
      molecule increases. The conformational behavior of freely rotatable single bonds,
      specially those within a sugar ring, is more "sharp" in larger structures.

PMID- 8877570
TI  - Geriatric education in medical oncology.

PMID- 8877571
TI  - Preceptorship, mentorship, and the adult learner in medical and health sciences
      education.
AB  - Preceptorship and mentorship are both based on principles of adult education and
      involve experiential, student-centered learning. Preceptorial relationships are
      especially useful in developing the practical skills of students. The preceptor
      works either with small groups of students or one-on-one with individual
      students, and serves as a teacher, role model, and evaluator. Preceptorial
      relationships between a teacher and a student are relatively short, and generally
      span the duration of a course or student rotation. Mentoring involves an intense,
      global, and long-term relationship between a mentor and a protege/e, and
      encompasses both professional and personal domains. It spans several years and
      may extend far beyond the period of the structured mentorship. The mentor serves
      as a teacher, role model, coach, and confidant for the protege/e and works one-on
      one with a protege/e to achieve various outcomes. Both parties reap significant
      rewards as a result of the mentorship, and are transformed in the process.
      Preceptors and mentors must be appropriately selected and adequately trained.
      Comprehensive faculty development courses and workshops should be designed and
      implemented to enhance the requisite skills of both groups. The effectiveness of
      preceptorship and mentorship needs to be continually assessed and appropriate
      steps taken to further enhance these special educational options. Both options
      should be included in medical and health sciences education to train competent
      and well-rounded professionals for the future.

PMID- 8877572
TI  - An adult education model for training third-year medical students in use of the
      Physician Data Query (PDQ) System.
AB  - BACKGROUND AND METHODS: An adult education model was developed to familiarize
      third-year medical students with the Physician Data Query (PDQ) system, a
      computerized, full-text database of state-of-the-art cancer information developed
      by the National Cancer Institute. The educational model was designed in
      collaboration with a medical librarian and was implemented within the context of
      a busy surgery clerkship using only modest resources that were readily available
      within the medical school. RESULTS: During three years, 275 medical students
      participated in the exercise and evaluated both the PDQ system and the
      educational model. Overall, 87% of the students considered the PDQ system to be a
      valuable source of information, and 84% anticipated using PDQ after completing
      their surgical rotations. Ninety-six percent of the students agreed that the
      objectives of the exercise were met. CONCLUSIONS: This article provides a
      description of the educational model and discusses the principles of adult
      education and andragogy on which it was developed. The importance of emphasizing
      the process of learning as well as the content is described relative to self
      directed and life-long learning.

PMID- 8877573
TI  - Educational program in palliative and hospice care at the University of Maryland
      School of Medicine.
AB  - BACKGROUND: The objective of this enterprise was and is to develop a validatable
      educational program on palliative and hospice care with a multidisciplinary
      perspective for the University of Maryland School of Medicine. METHODS: An
      interdisciplinary education committee consisting of experts in palliative and
      hospice care and an expert in educational design and evaluation was established
      to develop the program. Program development, which is ongoing, includes a
      comprehensive instructional design phase, vertical integration of the program
      into the medical school curriculum, and outcome evaluation. RESULTS: The
      instructional design phase has been accomplished; hence, the focus of this paper
      is on this aspect of program development. In addition, some integration of
      specific content areas into the medical school curriculum has been implemented.
      CONCLUSIONS: When complete, the program will focus on developing skills and
      knowledge using a variety of interactive educational modalities, including
      problem-based learning, case study discussions, role playing, and practical
      experience at hospice and palliative care sites. Topics to be covered are symptom
      control, the compassionate approach to patient care, communication between
      physicians and patients or family members, professional collaboration on a
      multidisciplinary palliative care team, ethical and legal issues pertaining to
      end-of-life care, and the value of palliative medicine as a profession.

PMID- 8877574
TI  - The impact of distribution of a patient-education pamphlet in a multidisciplinary
      breast clinic.
AB  - STUDY GOAL: To determine the impact of the distribution of patient-education
      pamphlets to women with benign breast conditions in a large urban
      multidisciplinary breast clinic. METHODS: It is clinic policy to administer such
      materials at the first patient visit for these conditions. A standardized
      telephone interview was conducted with a random sample of 50 such patients at a
      mean of five months after that visit (range 1-12 months). RESULTS: While only 29
      of the 50 women interviewed reported receiving such materials, 27 of these 29
      women reported reading them. The patient's level of education and whether the
      patient had friends/relatives with breast cancer were not different between the
      women who had read the pamphlets and the women who had not (p = NS). The women
      who had received and read the material scored significantly better than did women
      who had not on a brief breast cancer screening questionnaire (p = 0.027). Of the
      former, all but three found the information of use; three-fourths of such women
      rated the materials 8 or higher on an increasing-usefulness scale of 1-10. The
      most frequently reported benefit gained from the materials was the proper conduct
      of breast self-examination. Overall patient satisfaction with the pamphlets was
      91%. Half of the women receiving such materials shared them with other women.
      CONCLUSIONS: Patient-education pamphlets distributed at a multidisciplinary
      breast clinic result in high patient satisfaction and better patient knowledge of
      breast health. However, these materials were received and read by patients less
      often than was expected by staff. Because 82% of all women interviewed reported
      that the clinic staff, the distributed pamphlets, and other reading materials
      were their best sources of information, it is further concluded that the
      distribution of such materials is an important function of a multidisciplinary
      breast clinic.

PMID- 8877575
TI  - How to prepare cancer patients for potentially threatening medical procedures:
      consensus guidelines. NSW Cancer Council Cancer Education Research Program.
AB  - BACKGROUND: Cancer patients face a frightening array of potentially threatening
      medical interventions. While the need to prepare patients for such procedures is
      widely acknowledged, there have been few attempts to clearly specify in detail
      what adequate preparation entails. METHODS: This study sought to develop a set of
      guidelines on how to prepare cancer patients for potentially threatening medical
      procedures. These guidelines were extensively reviewed and modified by a
      consensus panel of experts. The guidelines were then rated by 101 cancer
      patients. RESULTS AND CONCLUSIONS: These ratings led to further modification of
      the guidelines, the final version of which was developed into a training module
      for junior medical officers in New South Wales.

PMID- 8877576
TI  - Urban-based Native American cancer-control activities: services and perceptions.
AB  - BACKGROUND: Cancer has become a significant health concern in American Indian
      communities. Over the past several decades Native peoples have experienced
      significant increases in life expectancy and, with these gains, significant
      increases in cancer incidence and mortality. Limited data are available
      concerning cancer-control activities accessible to American Indian communities.
      Even less is known about control programs in place for American Indians resident
      in urban areas, where more that half of all Native peoples reside. METHODS: To
      ascertain the extent of available services and perceptions of health directors, a
      survey of all Indian-Health-Service-recognized urban clinics was undertaken.
      RESULTS: Results indicate that the cancer needs of American Indians resident in
      urban areas are not being adequately addressed. Only one-third of urban health
      directors reported perceived increases in cancer incidence and mortality rates.
      The directors ranked cancer fifth among seven health problems in terms of their
      clinics' commitment to addressing them. Findings from this study are juxtaposed
      with whose obtained in a separate survey of reservation-based health directors.
      CONCLUSIONS: Results indicate a need to develop more responsive cancer-control
      programs in Indian country and to sensitize researchers to other health needs of
      these communities.

PMID- 8877577
TI  - Social support and adherence behavior among women with abnormal Pap smears.
AB  - BACKGROUND: Studies of hypertension, diabetes, and diet have indicated a
      relationship between social support and adherence to treatment regimens.
      Estimates of nonadherence following abnormal Pap test results range as high as
      40%. In this study, the relationship between social support and adherence
      behavior was examined in a population of low-income, public-health-department
      patients with abnormal Pap smears. METHODS: Medical record reviews ascertained
      adherence behavior and interviews determined receipt of social support for 498
      women. RESULTS: Related to adherence were: receipt of any social support; receipt
      of each of three types of support (informational, emotional, and tangible
      support); amount of support received; satisfaction with support; and source of
      support. Reported need for support was not related to adherence behavior. Receipt
      of social support was more strongly related to adherence when the woman's
      emotional response to the notification of the abnormal Pap smear was greater, and
      when acculturation was higher (among Latinas). Knowledge of the results of the
      Pap test was found to be an intervening variable between receipt of informational
      support and adherence. Knowledge of the purpose of the Pap smear was found to be
      independently related to adherence. Among black women, emotional support was most
      strongly related to adherence, while among Latinas, tangible support was most
      strongly related to adherence. In a multivariate model, Pap-test knowledge and
      the interaction between emotional response and receipt of any social support were
      significantly related to adherence. CONCLUSIONS: Findings suggest that supportive
      interventions, including provision of medical information, emotional support,
      child care, and transportation, could help to reduce nonadherence.

PMID- 8877578
TI  - Demographic, psychosocial, and objective risk factors related to perceived risk
      of skin cancer.
AB  - BACKGROUND AND METHODS: The present study examined the ways in which demographic,
      psychosocial, and objective risk factors were related to perceived risk of skin
      cancer among 384 hospital employees who participated in a screening program. It
      was hypothesized that pyschosocial risk factors would account for a significant
      portion of the variance in risk perception beyond that accounted for by the other
      risk factors. RESULTS: The risk factors accounted for approximately 44% of the
      variance in risk perception. Psychosocial risk factors accounted for a
      statistically significant portion of the variance in risk perception beyond that
      accounted for by other risk factors. Worry, family history of skin cancer, and
      race/ethnicity were most strongly related to perceived risk. CONCLUSIONS: Results
      are discussed in terms of the need for educational programs that emphasize the
      relationship between level of risk and skin cancer and provide specific
      information regarding steps that can be taken to prevent skin cancer.

PMID- 8877579
TI  - Analysis of lysophophatidylcholine-induced endothelial dysfunction.
AB  - Endothelial dysfunction caused by the early atherosclerotic process or by
      endothelial exposure to atherogenic lipids, including lysophosphatidylcholine
      (lysoPC), is characterized by a selective impairment of responses mediated by the
      pertussis toxin-sensitive Gi-2 protein. Experiments were performed to analyze the
      mechanisms underlying this effect. Bradykinin (BK: Gi-2 protein-independent),
      serotonin (5-HT: Gi-2 protein-dependent), or direct activation of the G(i-2)
      protein by mastoparan increased the release of endothelium-derived nitric oxide
      (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release
      of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan.
      LysoPC did not increase production of superoxide radicals detected by lucigenin
      enhanced chemiluminescence. Western blot analysis showed no difference in the
      level of immunoreactive Gi alpha-2 between control and lysoPC-treated cells.
      Activation of the Gi-2 protein by serotonergic or alpha 2-adrenoceptor
      stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of Gi alpha
      2 protein in membranes from control but not lysoPC-treated cells. However, direct
      activation of the Gi-2 protein by mastoparan inhibited the ADP-ribosylation in
      membranes from control and lysoPC-treated cells. The toxin-catalyzed reaction was
      reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the
      ability of endothelin to increase GTP gamma S binding to the Gi-2 protein but did
      not affect the activity of mastoparan. These results suggest that lysoPC inhibits
      a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with
      receptor:Gi-2-protein uncoupling.

PMID- 8877580
TI  - Effects of ranolazine on the exercise capacity of rats with chronic heart failure
      induced by myocardial infarction.
AB  - Ranolazine was previously shown to stimulate cardiac glucose oxidation.
      Dichloroacetate (DCA) also does and was shown to improve exercise capacity in
      animals, but it has long-term toxicity problems. To test the hypothesis that
      ranolazine would increase exercise performance in the chronic heart failure (CHF)
      condition, we compared the exercise endurance capacities of rats with a
      surgically induced myocardial infarction (MI) with those of noninfarcted sham
      operated (Sham) controls both before and after 14 and 28 days of drug
      administration. Chronic administration of ranolazine, 50 mg/kg twice daily
      (b.i.d.) oral, significantly reduced the endurance capacities of both Sham and MI
      rats (measured after a 12-h fast to reduce liver glycogen stores), as indicated
      by the reductions in run times to fatigue during a progressive treadmill test.
      Ranolazine produced reductions in resting plasma lactate and glucose
      concentrations of animals fasted for 12 h (consistent with stimulating glucose
      oxidation); however, tissue glycogen concentrations measured in various locomotor
      muscles located in the animal's hindlimb were unaffected when measured 48 h after
      the last treadmill test and after 12 h of fasting. Chronic administration of
      ranolazine did not increase the endurance capacity of rats with CHF induced by MI
      at the dosage and with the protocol used. To the contrary, the chronic
      administration of ranolazine appears to reduce the work capacity of all rats,
      suggesting that this drug may not be useful therapeutically in the treatment of
      CHF. Whether the decrements in endurance capacity produced by ranolazine are
      related to the high plasma concentrations of the drug produced in this study as
      compared with previous studies in humans remains subject to further
      experimentation.

PMID- 8877581
TI  - Mechanisms of prostaglandin F2 alpha and histamine-induced contractions in human
      chorionic vasculature.
AB  - We investigated the signaling pathways modulating histamine- and prostaglandin F2
      alpha (PGF2 alpha)-induced contractions of human chorionic vasculature. Neomycin,
      a phospholipase C (PLC) inhibitor, attenuated PGF2 alpha and histamine
      contractile responses 40 and 60%, respectively. AIF4-, a G protein stimulant,
      induced a strong contraction alone but blocked histamine- and PGF2 alpha-induced
      contractions. Staurosporine (100 nM), a protein kinase C (PKC) inhibitor,
      attenuated the PGF2 alpha-dependent contractions by 50% but did not affect the
      histamine response. However, higher nonspecific inhibitory concentrations of
      staurosporine (1-2 microM) abolished histamine and PGF2 alpha contractile
      responses, presumably by inhibiting other protein kinases. Although, the PKC
      phorbol 12-myristate 13-acetate (PMA) did not affect basal tension or PGF2 alpha
      dependent contractions, the histamine response was attenuated by 30%. Sodium
      nitroprusside (SNP), a guanylyl cyclase stimulant, strongly attenuated histamine-
      and PGF2 alpha-induced contractions. Tension increases were similarly attenuated
      by forskolin and isobutylmethylxanthine (IBMX), which increase intracellular
      cyclic AMP. In vessel rings prelabeled with [3H]myoinositol, PGF2 alpha and
      histamine increased [3H]inositol phosphate (IP) production 400 and 100%,
      respectively, indicating that PLC is stimulated by both agonists. Neomycin
      inhibited histamine- and PGF2 alpha-induced increases in [3H]IP production 60 and
      40%, respectively. Staurosporine (0.1-1 microM) and PMA did not affect histamine-
      or PGF2 alpha-stimulated IP production. AIF4-alone increased IP production but
      blocked histamine- and PGF(2 alpha)-dependent IP increases. These observations
      suggest that at least part of the contractile responses due to PGF2 alpha and
      histamine are associated with stimulation of PLC through an AIF4(-)-sensitive G
      protein. The role of PKC is variable, because PGF2 alpha but not histamine
      tension responses were attenuated by PKC inhibition. In addition, therapeutic
      agents that increase cyclic AMP and cyclic GMP attenuated histamine- and PGF2
      alpha-induced contractions in human chorionic vasculature, although histamine
      responses were relatively more sensitive to these agents.

PMID- 8877582
TI  - Arterial versus venous metabolism of nitroglycerin to nitric oxide: a possible
      explanation of organic nitrate venoselectivity.
AB  - Nitroglycerin (NTG) and other organic nitrates are predominant venodilators in
      vivo and in vitro. This selectivity is an important determinant of their ability
      to relieve angina and congestive heart failure symptoms, but the mechanism of
      this phenomenon is unknown. Because organic nitrate vasodilation occurs through
      metabolism to nitric oxide (NO), we tested the hypothesis that their
      venoselectivity is related to an enrichment of the pertinent enzyme in venous
      tissue. Enzymatic conversion of NTG to NO was examined in microsomal fractions
      from bovine aorta as compared with vena cava tissues. NTG (150, 450, or 900
      microM) was incubated with 1 mg microsomal protein and glutathione (13 microM),
      and cumulative NO production was measured for 5 h. When enzyme velocities were
      normalized to microsomal protein, statistical significance was not observed
      between fractions from aorta and those from vena cava. However, when enzyme
      activity was normalized to tissue weight or total homogenate protein,
      statistically higher activity was observed in the venous tissue (p < 0.05). These
      differences were greatest (two- to three-fold higher in vena cava at all three
      NTG concentrations, p < 0.01) when enzyme velocity was normalized to the initial
      cellular content of the homogenates (i.e., homogenate DNA concentrations). These
      results suggest that organic nitrate venoselectivity may be at least partly
      explained by enrichment of the bioactivating enzyme in venous smooth muscle
      cells.

PMID- 8877583
TI  - N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet
      aggregation.
AB  - N-Acetylcysteine (N-AC) potentiates the systemic and coronary hemodynamic and
      antianginal effects of nitroglycerin (NGT) in humans; NTG/N-AC reduces the
      incidence of acute myocardial infarction in patients with unstable angina
      pectoris. Although previous studies have demonstrated that NTG exerts
      antiaggregatory effects on platelets, little information is available concerning
      the possible potentiation by N-AC of NTG antiplatelet effects. In the present
      study, we examined the in vitro effects of NTG and the combination of NTG with N
      AC on reversal of ADP-induced aggregation in platelet-rich plasma (PRP) obtained
      from normal subjects and patients with stable angina pectoris. We also examined
      the potential effect of background aspirin therapy on this interaction. NTG,
      added to platelets 0.5 min after the beginning of aggregation, suppressed the
      incipient aggregation and provoked the appearance of a disaggregation phase,
      resulting in a concentration-dependent reversal of platelet aggregation. Platelet
      responsiveness to NTG was significantly less (p < 0.01) in both groups of
      patients (receiving and not receiving aspirin) as compared with normal subjects.
      N-AC (10(-5) M), which did not in itself affect aggregation, induced a threefold
      potentiation (p < 0.05) of the antiaggregating effect of NTG that was similar in
      degree for all tested groups of individuals. This potentiation of the
      antiplatelet effects of NTG by N-AC may contribute to the efficacy of combined
      NTG/N-AC therapy in patients with acute ischemic syndromes.

PMID- 8877584
TI  - Cardiovascular and renal effects of endothelin B receptor selective agonists in
      spontaneously hypertensive rats.
AB  - Renal effects of endothelin (ET)-3 have been described in normotensive but not
      spontaneously hypertensive rats (SHR). Infusion (170 ng/kg/min) of the ETB
      receptor selective agonists ET-3 and sarafotoxin S6c (SS6c) was used to
      investigate ETB receptor modulation of renal function in SHR. ET-3 decreased
      glomerular filtration rate (GFR) and renal plasma flow (RPF) by approximately 95%
      (0.1 +/- 0.01 and 0.1 +/- 0.02 ml/min, respectively) versus vehicle (1.3 +/- 0.08
      and 3.6 +/- 0.23, respectively) in SHR. ET-3 exerted a biphasic effect on urine
      flow (UV); an initial increase and then a decrease (vehicle, 4.2 +/- 0.55; ET-3,
      0.2 +/- 0.09 microliter/min). ET-3 increased mean arterial pressure (vehicle, 159
      +/- 4.1; ET-3, 174 +/- 3.1 mm Hg). SS6c decreased GFR and RPF by approximately
      60% (0.8 +/- 0.12 and 2.0 +/- 0.18 ml/min, respectively) versus vehicle (2.0 +/-
      0.19 and 5.2 +/- 0.45, respectively). UV did not change. Depressor effects of
      SS6c were observed (vehicle, 154 +/- 1.5; SS6c, 127 +/- 3.1 mm Hg). The ETB
      receptor selective agonists ET-3 and SS6c markedly decreased GFR and RPF in SHR,
      suggesting that endogenous ET-3 may modulate renal function through ETB receptors
      in SHR.

PMID- 8877585
TI  - Barium-induced diastolic depolarization and controlling mechanisms in guinea pig
      ventricular muscle.
AB  - Barium-induced diastolic depolarization (Ba(2+)-DD) and its modulation were
      studied in guinea pig papillary muscle and single ventricular myocytes. In
      papillary muscles, Cs+ (4 mM) abolished the DD induced by Ba2+ (0.05-0.2 mM) by
      abolishing the undershoot at the end of the action potential (AP; consistent with
      a block of an outward current). Acetylcholine (ACh 1 microM) had little effect on
      Ba(2+)-DD, whereas norepinephrine (NE 1 microM) enhanced it by increasing the
      undershoot and by inducing an oscillatory potential. Low [Ca2+]o (0.54 mM)
      decreased the resting potential and increased Ba(2+)-DD amplitude. High [Ca2+]o
      (8.1 mM) had opposite effects. Cs+ also reduced Ba(2+)-DD in low [Ca2+]o. In
      isolated myocytes, Ba(2+)-DD and the pacemaker current induced by Ba2+ (Ba(2+)
      IKdd) increased on depolarization and reversed on hyperpolarization. Although not
      significantly, high [Ca2+]o slightly decreased and low [Ca2+]o slightly increased
      Ba(2+)-IKdd. Cd2+ markedly reduced the slow inward current ICa and the AP
      duration (APD), but did not affect Ba(2+)-IKdd. We conclude that Ba(2+)-DD (a) is
      entirely due to a voltage- and time-dependent decrease in gK1, since it is
      abolished by Cs+ (no contribution of a nonblocked decaying IK) by eliminating the
      undershoot (no If), (b) is potentiated by NE through an increased undershoot and
      an oscillatory potential, (c) is modified by high and low [Ca2+]o mostly through
      changes in the resting potential, and (d) is not affected by the block of the
      slow channel by Cd2+.

PMID- 8877586
TI  - Renal and depressor activity of C-natriuretic peptide in conscious monkeys:
      effects of enzyme inhibitors.
AB  - The depressor and renal responses to C-type natriuretic peptide (CNP) were
      determined in conscious cynomolgus monkeys treated with vehicle or inhibitors of
      neutral endopeptidase EC 3.4.24.11 (NEP) and angiotensin-converting enzyme (ACE).
      The NEP inhibitor SQ 28603 (100 mumol/kg intravenously, i.v.) significantly (p <
      0.05) enhanced the depressor responses to 1 and 10 nmol/ kg i.v. CNP from -2 +/-
      3 to -22 +/- 10 mm Hg and from -16 +/- 4 to -66 +/- 4 mm Hg, respectively. SQ
      28603 also significantly increased the cyclic GMP responses to 1 and 10 nmol/kg
      CNP from 1.4 +/- 1.6 to 11.0 +/- 2.0 nmol/2 h and from 4.2 +/- 0.5 to 53.3 +/-
      12.1 nmol/2 h, respectively. Furthermore, the NEP inhibitor significantly
      increased the natriuretic activity of 1 and 10 nmol/kg i.v. CNP from 235 +/- 99
      to 760 +/- 60 microEq/2 h and from 399 +/- 208 to 1,036 +/- 79 microEq/2 h,
      respectively. A positive correlation between the cumulative natriuretic and
      cyclic GMP responses suggested a cyclic GMP-mediated mechanism. These data are
      consistent with the protection of CNP from degradation by renal NEP. Inhibition
      of ACE by 100 mumol/kg i.v. captopril did not significantly alter the depressor
      or renal activities of 1 nmol/kg of CNP, neither did it alter the potentiation of
      CNP activity by SQ 28603. The potentiation of the depressor, cyclic GMP, and
      natriuretic responses to CNP in nonhuman primates by SQ 28603 suggested that NEP
      is an important mechanism for in vivo inactivation of natriuretic peptides,
      including CNP.

PMID- 8877587
TI  - Glucose tolerance and postprandial glucose and insulin kinetics in rats with
      short- and long-term alpha 1-adrenergic blockade.
AB  - The present study was designed to evaluate the acute and chronic effects of the
      alpha 1-adrenergic antagonist prazosin (Praz) on glucose tolerance and on
      postprandial plasma glucose and insulin kinetics. Rats were fed a high sucrose
      diet for 3 weeks, to which Praz (3 mg/kg/day) was added or not. They were then
      accustomed to ingest a meal 1 h after a single intraperitoneal (i.p.) injection
      of saline or Praz (1 mg/kg). Plasma levels of glucose and insulin were recorded
      at various times after meal intake. In addition, a fasting intravenous glucose
      tolerance test (IVGTT) was performed. In the chronic control cohort, pre-IVGTT
      plasma glucose and insulin levels were slightly but significantly higher after
      acute Praz than after acute saline administration. Factorial analysis of variance
      (ANOVA) showed that the increase in plasma glucose and insulin after intravenous
      (i.v.) glucose administration was also slightly greater in the animals that
      received acute Praz than in their saline counterparts. In contrast, after chronic
      treatment with Praz, pre- and post-IVGTT plasma glucose and insulin
      concentrations were identical in groups acutely injected with saline or Praz. In
      the chronic control cohort, preprandial plasma glucose and insulin measured in a
      sample collected before acute injection of saline or Praz were similar in both
      groups. The postprandial increase in plasma glucose and insulin was potentiated
      by the acute administration of Praz. Fasting plasma glucose and insulin
      concentrations were also similar in both groups chronically treated with Praz,
      and acute administration of the blocker still potentiated the increase in plasma
      glucose and insulin that followed meal intake. Chronic treatment alone did not
      affect postprandial glucose and insulin concentrations, and acute injection of
      Praz had comparable effects whether rats were chronically treated with the
      blocker or not. Therefore, potentiation of the glucose and insulin response to
      meal intake by Praz persisted after chronic treatment but required the acute
      presence of the blocker. However, repeated exposure to acute bouts of
      postprandial hyperinsulinemia induced by Praz did not lead to deterioration of
      insulin sensitivity or of the capacity of the pancreas to secrete insulin, as
      suggested by a normal response of glucose and insulin to IVGTT.

PMID- 8877588
TI  - Carvedilol protects against lethal reperfusion injury through antiadrenergic
      mechanisms.
AB  - We examined the effect of carvedilol as compared with that of a combination of
      propranolol and doxazosin on lethal reperfusion injury in 21 feline hearts
      subjected to 40-min regional ischemia and 180-min reperfusion. A control group (n
      = 7) was compared with one group given carvedilol, a nonselective beta - and
      alpha 1-adrenoceptor blocker and antioxidant (n = 7) and another group given
      nonselective beta - and alpha 1-adrenoceptor blockade with propranolol and
      doxazosin (n = 7) during initial reperfusion. Infarct size (IS: percent of area
      at risk, AAR) determined by staining the myocardium with triphenyl tetrazolium
      chloride (TTC), was reduced both in the carvedilol-treated group (median 1.8%, p
      < 0.05) and in the group given propranolol/doxazosin (median 6.5%, p < 0.05) as
      compared with controls (median 14.4%). Treatment with carvedilol reduced IS more
      than did treatment with propranolol/doxazosin (p < 0.05). Longitudinal segment
      shortening measured with sonomicrometry, improved in both treatment groups as
      compared with control (p < 0.05), but to a greater extent in the group treated
      with carvedilol. In circumferential segments, only carvedilol significantly
      improved segment shortening. The incidence of ventricular fibrillation (VF) after
      reperfusion was reduced in both treatment groups as compared with control.
      Oxidized glutathione and thiobarbituric acid-reactive substances (TBARS) measured
      at the end of reperfusion did not differ between groups. Carvedilol protected
      against lethal reperfusion injury mainly through blockade of adrenoceptors.

PMID- 8877589
TI  - Studies of vascular tolerance to nitroglycerin: effects of N-acetylcysteine, NG
      monomethyl L-arginine, and endothelin-1.
AB  - Development of vascular tolerance to nitroglycerin (NTG) has been attributed to
      sulfhydryl (SH) depletion, guanylate cyclase desensitization, or both.
      Controversy regarding the precise contribution of these mechanisms may be due to
      variations in experimental design. To examine further the biochemical basis of
      NTG tolerance, norepinephrine (NE)-precontracted rat aortic rings were exposed to
      NTG (10(-5)M), which resulted in 84 +/- 6% relaxation. Other rings were first
      superfused with NTG (10(-6)M) and then contracted with NE. These rings showed a
      marked tolerance to the vasorelaxant effects of NTG (maximal relaxation 20 +/-
      5%, n = 15, p < 0.001 vs. control rings). Similar tolerance to NTG was observed
      when the vascular rings were first superfused with acetylcholine (ACh 10(-6)M),
      indicating cross-tolerance between ACh and NTG. Treatment of NTG-tolerant rings
      with N-acetylcysteine (NAC) (10(-5)M) did not restore vascular smooth muscle
      (VSM) relaxation in response to NTG (maximal relaxation 23 +/- 5%, n = 8),
      suggesting that SH depletion may not be the basis of NTG tolerance in these
      experiments. Parallel sets of NTG-tolerant aortic rings were contracted with
      endothelin-1 (ET-1, n = 5) or the endothelium-derived relaxing factor (EDRF)
      synthase inhibitor NG-monomethyl L-arginine (L-NMMA, 10(-4)M, n = 8). In both ET
      1- and L-NMMA-contracted rings, vascular relaxation in response to NTG was
      preserved (80 +/- 6 and 88 +/- 8% relaxation, respectively). Measurement of
      cyclic GMP in aortic rings showed marked accumulation on initial exposure of
      tissues to NTG (310 +/- 10 fmol/mg), whereas the NTG-tolerant rings showed much
      less cyclic GMP accumulation (48 +/- 29 fmol/mg). Rings contracted with L-NMMA or
      ET-1, but not NE, accumulated cyclic GMP when exposed to NTG (280 +/- 20
      fmol/mg). These data indicate that NTG tolerance develops on exposure of vascular
      rings superfused with NTG or ACh and is probably not related to tissue SH
      depletion. Contraction of NTG-tolerant rings with ET-1 or L-NMMA restores NTG
      mediated relaxation.

PMID- 8877590
TI  - Interactions of nonpeptide angiotensin II receptor antagonists at
      imidazoline/guanidinium receptor sites in rat forebrain.
AB  - Imidazoline/guanidinium receptive sites (IGRS) are shown to be present in the
      subfornical organ and hypothalamic arcuate nucleus by a derivative of cirazoline,
      2-(3-amino-4-[125I]iodophenoxy)methylimidazoline ([125I]AMIPI). Because many of
      the nonpeptide angiotensin II (Ang II) receptor antagonists contain imidazole
      ring structures, they may interact with IGRS. Therefore, we studied competitive
      activity of Ang II and several nonpeptide Ang II receptor antagonists [DuP 753
      (losartan), EXP 3174, CV11974, and PD123319] at IGRS in rat forebrain. The
      results showed specific binding of 944 +/- 169 fmol/mg protein in the subfornical
      organ (n = 11) and of 367 +/- 27 fmol/mg protein in the arcuate nucleus (n = 6)
      at 0.4 nM [125I]AMIPI, as defined by competition with 10 microM cirazoline.
      Specific [125I]AMIPI binding was competed for completely by 10 microM idazoxan or
      clonidine as further characterization of IGRS. Ang II and the nonpeptide AT1 and
      AT2 antagonists did not significantly compete for specific [125I]AMIPI binding in
      either brain region at concentrations of 10 microM (< 20% competition with each
      compound), which is 10- to 100-fold higher than the concentration necessary to
      compete completely for their respective Ang II receptor subtypes. Only at the
      highest concentration (100 microM) did losartan compete significantly for binding
      (56 +/- 8%). Therefore, Ang II receptor antagonists interact with IGRS in rat
      forebrain cardiovascular areas only at high concentrations.

PMID- 8877591
TI  - Sustained antiplatelet properties of nitroglycerin during hemodynamic tolerance
      in rats.
AB  - Organic nitrates possess important antiplatelet actions that are useful in the
      treatment of unstable angina and myocardial infarction, but the susceptibility of
      platelets to nitrate tolerance has not been extensively studied. In normal
      conscious rats, we showed that continuous infusion of nitroglycerin (NTG) at 10
      micrograms/min had no significant effect on mean arterial pressure (MAP) as
      compared with control, but hemodynamic tolerance could be demonstrated by MAP
      response to a bolus intravenous (i.v.) NTG challenge. By this criterion,
      continuous 8-h NTG infusion produced hemodynamic tolerance (a decrease in MAP
      response of 45.7 +/- 19.9%, p < 0.05), whereas D5W control and S-nitroso-N
      acetylpenicillamine (SNAP) infusions did not. During NTG infusion, platelet-rich
      plasma (PRP) cyclic GMP was increased by 41.4 +/- 13.6% as compared with control
      and remained increased throughout the infusion (p < 0.05). Bleeding time during a
      2-h infusion of NTG was 8.9 +/- 1.2 min as compared to 3.8 +/- 0.4 min in
      controls (p < 0.05). After 8-h of NTG infusion, the bleeding time was 10.2 +/-
      1.4 min versus 4.4 +/- 0.4 min in controls (p < 0.05). NTG also decreased the PRP
      platelet concentration by 30% in 8 h, whereas D5W had no effect. In vitro
      experiments showed that platelets in themselves do not produce significant
      amounts of cyclic GMP. These data indicate that the biochemical and
      antiaggregation effects of NTG on platelets are not diminished during hemodynamic
      tolerance and that these effects may be dependent on extraplatelet production of
      nitric oxide (NO).

PMID- 8877592
TI  - Central and peripheral effects of asymmetric dimethylarginine, an endogenous
      nitric oxide synthetase inhibitor.
AB  - We tested the hypothesis that the endogenous nitric oxide synthetase (NOS)
      inhibitor, asymmetric dimethylarginine (ADMA), regulates cardiovascular function
      by central mechanisms. In in vivo studies, rats received intracerebroventricular
      (i.c.v.) injection of isotonic saline, ADMA (1 mg), l-arginine (3 mg), and N
      omega-nitro-l-arginine methylester (l-NAME, 1 mg). Baroreflex function was then
      assessed by intravenous (i.v.) injection of phenylephrine. Central application of
      exogenous NOS inhibitor, l-NAME, increased mean arterial blood pressure and
      decreased heart rate. However, application of the endogenous NOS inhibitor, ADMA,
      decreased mean arterial blood pressure and heart rate simultaneously (-39 +/- 6
      mm Hg and -50 +/- 8 beats/min, respectively). Both l-NAME (i.c.v.) and ADMA
      (i.c.v.) significantly inhibited the baroreflex function, indicating a regulatory
      role of central nitric oxide in controlling baroreflex function. In contrast to
      the central effect, intravenous injection of ADMA caused dose-dependent increases
      in mean arterial blood pressure that could be blocked by l-NAME pretreatment. In
      vitro studies using aortic rings demonstrated that ADMA (10(-4)M) significantly
      increased the concentration of acetylcholine for the threshold response (EC15)
      and half-maximal response (EC50). This indicates that ADMA inhibits the
      constitutive isoform of NOS in the endothelium. ADMA may have functional
      importance in regulating cardiovascular function by mechanisms in addition to the
      inhibition of nitric oxide synthesis.

PMID- 8877593
TI  - Evidence of systemic neuropeptide Y release after carbachol administration into
      the posterior hypothalamic nucleus.
AB  - The unilateral microinjection of the cholinergic agonist carbachol (CCh) directly
      into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose
      dependent increase in mean arterial pressure (MAP). Blockade of peripheral alpha
      adrenoceptors and V1-vasopressin receptors completely inhibits this response,
      suggesting that the increase in MAP is mediated by increases in sympathoadrenal
      excitation and circulating vasopressin. Combining beta-adrenoceptor blockade with
      alpha-adrenoceptor and V1-vasopressin receptor blockade results in the return of
      a pressor response. To determine if neuropeptide Y (NPY) might be responsible for
      this increase, the putative NPY and irreversible alpha 1-adrenoceptor antagonist
      benextramine was added to alpha 2- and beta-adrenoceptor and V1-vasopressin
      receptor blockade provided by yohimbine, propranolol, and [D(CH2)5-Tyr(Me)]AVP
      (AVPX), respectively. Benextramine noncompetitively inhibited the pressor
      response to intravenous injection of NPY and the increase in MAP evoked by CCh
      microinjection into adrenergic and V1-vasopressin receptor-blocked rats, whereas
      benextramine competitively inhibited the pressor response to angiotensin II
      (AII). Furthermore, the combination of losartan, the selective AT1-AII receptor
      antagonist that completely blocked the increase in MAP evoked by intravenous AII,
      and adrenergic and V1-vasopressin receptor antagonists did not attenuate the
      pressor response evoked by CCh microinjection into the PHN or the increase in MAP
      evoked by intravenous injection of NPY. These results indicate that AII was not
      responsible for the CCh-evoked increase in MAP in the presence of adrenergic and
      V1-vasopressin receptor blockade. The similarity in the antagonism of the
      increase in MAP evoked by intravenous NPY injection and by CCh microinjection
      into the PHN of adrenergic- and V1-vasopressin receptor-blocked rats suggests
      that NPY might be released from sympathetic neurons after activation of the
      sympathetic nervous system by central administration of CCh into the PHN.

PMID- 8877594
TI  - Adrenomedullin dilates rat pulmonary artery rings during hypoxia: role of nitric
      oxide and vasodilator prostaglandins.
AB  - Hypoxia decreases vasorelaxation and leads to pulmonary arterial hypertension. A
      newly identified 52 amino-acid peptide adrenomedullin (ADM) exerts vasodilator
      effect in intact animals under normoxic condition. We studied the effect of human
      ADM on rat pulmonary arterial and aortic rings under normoxic and hypoxic
      conditions. During normoxia, ADM caused a concentration-dependent relaxation of
      precontracted aortic and pulmonary arterial rings; the relaxation was much more
      pronounced in pulmonary arterial rings and was abolished by the nitric oxide (NO)
      synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) and by
      deendothelialization. A fragment of ADM, ADM13-52, caused a degree of relaxation
      similar to that induced by ADM in pulmonary arterial rings, but not in the aortic
      rings, and the relaxation of pulmonary artery caused by ADM13-52 was not affected
      by the cyclooxygenase inhibitor indomethacin but was abolished by L-NAME and by
      deendothelialization. During hypoxia, ADM13-52 failed to relax pulmonary arterial
      rings, whereas ADM caused modest relaxation of pulmonary arterial rings (one
      third of the relaxation during normoxia), which was abolished by pretreatment
      with indomethacin. Our results indicate that the vasorelaxant effect of ADM is
      more pronounced in pulmonary artery than in the aorta; ADM has more potent
      vasodilator effect than ADM13-52 during hypoxia; ADM relaxes hypoxic pulmonary
      artery through an indomethacin-sensitive pathway; amino acids 1-12 in ADM must be
      present for relaxation of chronic hypoxic pulmonary arterial rings; and last, the
      presence of endothelium is necessary for the expression of ADM-mediated
      relaxation.

PMID- 8877595
TI  - Effects of antihypertensive drugs on the circadian blood pressure profile.
AB  - We compared the effect of beta-blockers, angiotensin-converting enzyme (ACE)
      inhibitors, and calcium antagonists on the circadian blood pressure (BP) profile
      in essential hypertension. We reviewed all studies published between 1980 and
      August 1993 reporting the circadian efficacy of antihypertensive drugs and using
      ambulatory BP monitoring. In all, 815 patients with essential hypertension were
      assessed in 51 studies of eight different beta-blockers, six ACE inhibitors, and
      eight calcium antagonists. As main outcome measures, relative (percentage) BP
      reductions during the day and at night were compared between the three classes of
      antihypertensive drugs. Results were also separated for different dosing schemes
      (once and more than once daily). With all three classes of antihypertensive
      agents, the percentage night BP reduction was approximately 1-3% less as compared
      with percentage reductions during the day. Only for systolic BP (SBP) of the
      calcium antagonists administered once daily was this difference significant
      [2.2%, confidence interval (CI) 0.3-4.0%, p < 0.05], due to a higher statistical
      power in this group of agents. Our results show that beta-blockers, ACE
      inhibitors, and calcium antagonists are comparably effective during the day and
      at night, and no evidence indicates that either of the three agents is preferable
      to obtain the best possible antihypertensive effect at night.

PMID- 8877596
TI  - Pharmacokinetic-pharmacodynamic model relating lisinopril plasma concentrations
      to regional hemodynamic effects in healthy volunteers.
AB  - In a previous placebo-controlled, randomized, double-blind, cross-over study
      performed in 6 healthy volunteers, we investigated the pharmacokinetics and
      pharmacodynamics of a single oral administration of two doses (5 and 20 mg) of
      the angiotensin-converting enzyme inhibitor (ACEI), lisinopril. The purpose of
      the present study was to investigate the relation between lisinopril plasma
      concentrations (C, ng/ml), and lisinopril-induced effects on plasma converting
      enzyme activity (PCEA, nmol/ml/min), brachial artery flow (BAF, ml/min), and
      brachial vascular resistance (BVR, mm Hg . s/ml). PCEA and BVR were expressed in
      percent changes from initial values and BAF was expressed in absolute values.
      Effects (E) were related to C by the Hill model: E = Emax . C gamma/CE50 gamma +
      C gamma). For PCEA, the model was fitted to the data of both doses
      simultaneously. Emax was fixed at -100%, and we obtained (mean +/- SD) CE50 = 1.4
      +/- 0.6 ng/ml and gamma = 0.6 +/- 0.1. For BAF and BVR, the model was fitted to
      the data of the 20-mg dose for 5 subjects and to those of the 5-mg dose for 1
      subject. We obtained Emax = 45 +/- 20 ml/min, CE50 = 24.0 +/- 12.4 ng/ml, and
      gamma = 3.2 +/- 1.3 for BAF, and Emax = -45 +/- 15%, CE50 = 22.0 +/- 10.2 ng/ml,
      and gamma = 3.1 +/- 1.1 for BVR. Therefore, the concentration-effect relations
      for BVR (or BAF) and PCEA display quite different shapes (CE50, gamma), which
      emphasizes the necessity of performing pharmacokinetic-pharmacodynamic (PK-PD)
      modeling on hemodynamic parameters to determine the optimal dosages of ACEIs.

PMID- 8877597
TI  - Distribution of neuronal populations containing neurofilament protein and calcium
      binding proteins in the canine neocortex: regional analysis and cell typology.
AB  - Neurophysiological experiments in carnivores have revealed the existence of a
      large number of cortical regions and an organization of sensory systems quite
      similar to that found in primates. However, the cyto- and chemoarchitecture of
      the cerebral cortex is relatively poorly known in carnivores. We analyzed the
      distribution and typology of classes of neurons containing neurofilament protein
      or the calcium-binding proteins parvalbumin, calbindin, and calretinin in six
      neocortical regions of the dog. In all these areas, neurofilament protein was
      present in a subpopulation of medium-to-large size pyramidal neurons
      predominantly distributed in layers III and V. Parvalbumin was present in a large
      population of morphologically diverse interneurons. Small ovoid and multipolar
      neurons were observed throughout the cortical layers, but predominated in layers
      II and IV. Layers III and V-VI were characterized by the presence of larger and
      intensely immunoreactive neurons with bitufted or multipolar morphology, and
      layers V-VI also contained large multipolar neurons. Calbindin was observed in
      small round and multipolar interneurons in layer II, and typical double bouquet
      cells in layer III. Layers IV-VI contained isolated double bouquet cells and
      large multipolar neurons. A few calbindin-immunoreactive pyramidal neurons were
      also observed in layer V. Calretinin was localized in bipolar and double bouquet
      cells in layers II and upper III. The lower part of layer III and layers IV-VI
      contained rare calretinin-immunoreactive neurons. In some areas, layer III
      displayed a few large isolated multipolar neurons and pyramidal neurons
      containing calretinin. In addition, the results show that there is a substantial
      degree of variability in the distribution of these proteins among cortical
      regions, and that although they are found in morphologically comparable neuronal
      types in dog, monkeys, and humans, many differences exist in their regional
      distribution patterns between carnivores and primates.

PMID- 8877598
TI  - Distribution of terminal fields stained for zinc in the neocortex of the rat.
AB  - Staining for zinc in terminal fields of the rat neocortex was studied by applying
      the sulphide/silver histochemical method. The stain was arranged in a distinct
      layered pattern. Two bands of heavy reaction were found in deep layer 1 plus
      layers 2-3 and in upper layer 5. A band of moderate-to-heavy reaction was found
      in layer 6. Three bands of lighter staining were found in upper layer 1, layer 4
      and deep layer 5. The layers of reaction showed variations in width and intensity
      of staining from area to area. In the frontal and cingulate cortices and in the
      association cortices, the heavily stained bands were dominant over the narrow,
      inconspicuous, lightly stained bands. In contrast, in primary sensory regions
      (Par1, Oc1 and Te1), the lightly stained bands were wide and prominent. The
      sulphide/silver method gives a straightforward delimitation of many cortical
      areas and reveals a clear distinction between (A) allocortical and isocortical
      areas, and (B) primary sensory areas, secondary or association areas, and
      prefrontal plus motor areas. The presence of vivid bands of staining for zinc
      appears to be linked to areas with prominent pyramidal layers.

PMID- 8877599
TI  - Acetylcholine innervation of sensory and motor neocortical areas in adult cat: a
      choline acetyltransferase immunohistochemical study.
AB  - Light microscopic choline acetyltransferase (ChAT) immunocytochemistry was used
      to examine the distribution of the acetylcholine innervation in primary motor (4
      gamma) and sensory (3a, 3b, 41 and 17) cortical areas of adult cat. In every
      area, scattered immuno-reactive cell bodies were present and a relatively dense
      meshwork of ChAT immunoreactive axons pervaded the whole cortical thickness.
      These axons were generally thin and bore innumerable varicosities of different
      sizes. A few thicker and smoother fibers and occasional clusters of unusually
      large varicosities were also visible. Overall, area 17 was less densely
      innervated than the other areas. In each area, layer I showed the densest
      innervation. Innervation of underlying layers was rather uniform in area 17, but
      patterned in other areas. In areas 4 gamma and 3a, layers II, upper III and V
      showed preferential innervation. Innervation of layer IV was the strongest in
      areas 3b and 41. Area 3a was transitional between 4 gamma and 3b. Except in area
      17, the laminar pattern of acetylcholinesterase staining was consistent with that
      of ChAT. In the light of current data on the distribution of this cortical
      innervation in different species, and of its presumed ultrastructural features,
      it appears likely that such regional and laminar features subtend widespread,
      modulatory roles of ACh.

PMID- 8877601
TI  - Pediatric movement disorders: newer therapeutic strategies.

PMID- 8877600
TI  - Pharmacological modulations of adrenergic phenotype in medullary C2 and C3 cell
      groups of adult rat.
AB  - The adrenergic phenotype was analysed in the rat's rostral dorsomedial medulla
      under normal conditions and 3 days after a single intraperitoneal injection of an
      eburnamine derivative, RU 24722, which increases tyrosine hydroxylase protein
      expression in the rostral portion of the nucleus tractus solitarius. This
      approach was investigated by a double immunofluorescence labelling of tyrosine
      hydroxylase and phenylethanolamine N-methyltransferase proteins. Under normal
      conditions, most adrenergic cell bodies are anatomically distributed in the
      dorsal and rostral medulla oblongata between the rostral part of the dorsal motor
      nucleus of the vagus nerve and the medial longitudinal fasciculus. Adrenergic
      neurons detected in this medullar region were distributed between both cell
      groups. Three days after the pharmacological RU 24722 treatment, an upregulation
      in tyrosine hydroxylase and phenylethanolamine N-methyltransferase protein
      expression was detected in both cell groups characterized by a highly increased
      number of tyrosine hydroxylase- and phenylethanolamine N-methyltransferase
      containing cell bodies. The number of TH-mRNA containing neurons was also
      increased, indicating the transcriptional level of this regulation. These results
      demonstrated a particular neuronal plasticity of adrenergic phenotype in the
      medullary cell groups of adult rat.

PMID- 8877602
TI  - Antidyskinetic drug therapy for pediatric movement disorders.
AB  - The pharmacologic armamentarium used to treat dyskinesias in childhood is
      increasing. Anticonvulsant drugs as a class are still some of the broadest
      spectrum antidyskinetic agents, probably because the class includes so many
      differently acting drugs or because dyskinesias are manifestations of subcortical
      electrical events. This group is enhanced by recent developments in gamma
      aminobutyric acid and glutamate receptor pharmacology, which promise new
      antidyskinetic drugs. Other drugs acting at receptors for monoamines (dopamine,
      norepinephrine, and serotonin), acetylcholine, opioids, or histamine may provide
      symptomatic improvement. Fewer pharmacotherapies address the underlying
      pathophysiology of movement disorders. Of these, drugs or biologicals for
      immunomodulation are the most developed, but the group also includes
      antioxidants, cofactors, metabolic inhibitors, and chelators. There is potential
      for drugs that block the neurotoxic effects of glutamate to treat movement
      disorders and reverse or prevent brain injury. Peripheral blockade of focal
      dyskinesias through botulinum toxin offers a useful alternative to drugs in some
      patients.

PMID- 8877603
TI  - Comparison of simultaneous versus delayed ventriculoperitoneal shunt insertion in
      children undergoing myelomeningocele repair.
AB  - The timing of cerebrospinal fluid shunt insertion for those neonates with
      hydrocephalus in association with myelomeningocele remains controversial. To
      examine whether there was a difference in either the complication rate or mean
      hospital stay for neonates undergoing myelomeningocele repair and shunting under
      the same anesthetic (simultaneous group) versus those in whom shunt insertion was
      delayed for several days after myelomeningocele closure (sequential group), we
      reviewed the results obtained with these two approaches in a series of 69
      consecutive patients who underwent both myelomeningocele closure and shunt
      insertion at our institution between 1987 and 1993. Twenty-one infants underwent
      simultaneous myelomeningocele repair and shunting, and 48 underwent sequential
      procedures. The decision to shunt concurrently with myelomeningocele repair
      rather than in a delayed fashion was based primarily on surgeon preference rather
      than initial head circumference, which did not differ significantly between the
      two groups. The frequency and type of hydrocephalus-related complications (e.g.,
      wound leak, cerebrospinal fluid infection, or shunt malfunction) that occurred
      during the first 6 months after myelomeningocele closure were compared between
      the two groups. Neither the overall frequency of complications nor the frequency
      of cerebrospinal fluid infection, shunt malfunction, or symptomatic Chiari
      malformation differed significantly between the two groups. In contrast, there
      was a significantly higher rate of myelomeningocele wound leak in the sequential
      group versus the simultaneous group (eight versus zero; P = .05). Mean hospital
      stay for the sequential group was also significantly longer than the simultaneous
      group (22 days versus 13 days; P = .05). These results suggest that simultaneous
      myelomeningocele repair and ventriculoperitoneal shunt insertion reduces hospital
      stay and back wound morbidity in those patients with evidence of hydrocephalus at
      birth, without an inordinate increase in shunt-related complications.

PMID- 8877604
TI  - Clinical and magnetic resonance imaging features of L-2-hydroxyglutaric acidemia:
      report of three cases in comparison with Canavan disease.
AB  - We report three cases of L-2-hydroxyglutaric acidemia and three cases of Canavan
      disease. The L-2-hydroxyglutaric acidemia cases are the first biochemically
      proven Turkish cases. Magnetic resonance imaging findings in the cases and
      similarities between the two diseases are emphasized. Both diseases are
      characterized by predominant subcortical white-matter involvement and dentate
      nuclei lesions with variable basal ganglia involvement. Canavan disease differs
      from L-2-hydroxyglutaric acidemia by the presence of typical brainstem
      involvement.

PMID- 8877605
TI  - Treatment of neonatal seizures with carbamazepine.
AB  - Carbamazepine has been used in adults and children for over 30 years. In spite of
      an excellent therapeutic and side-effect profile in older children, it has never
      been used as a primary anticonvulsant in neonates. This is the first report of
      the long-term use of carbamazepine in neonates. Ten full-term neonates with two
      or more seizures due to hypoxic-ischemic encephalopathy were given 10 mg/kg of
      carbamazepine as a loading dose via nasogastric tube. Twenty-four hours later,
      the first five patients began a maintenance regimen of 21 mg/kg/daily, and the
      remaining five patients began a maintenance regimen of 15 mg/kg/daily, all via
      nasogastric tube. Therapy was continued for 3 to 9 months. Drug levels were
      monitored every 2 to 4 hours during the first 24 hours, and on days 2, 4, 8, 15,
      30, 45, and 60, and monthly thereafter. Absorption of carbamazepine was excellent
      even in sick neonates. Therapeutic levels were reached in 2 to 4 hours in all
      patients. Peak levels were achieved in 4 to 16 hours (mean, 9.2 +/- 4.2).
      Elimination half-life was 24.5 hours. Levels dropped precipitously around 8 to 15
      days and thereafter declined slowly over the next 3 months. Seizure control was
      excellent; only two patients had one seizure each during the first 10 hours.
      There were no gastrointestinal, hepatic, hematologic, renal, or dermatologic side
      effects. This preliminary study shows that carbamazepine may be an effective
      anticonvulsant for neonatal seizures.

PMID- 8877606
TI  - How do cryptogenic and symptomatic infantile spasms differ? Review of biochemical
      studies in Finnish patients.
AB  - Infants with cryptogenic infantile spasms seem to differ from those with
      symptomatic spasms in having a higher cerebrospinal fluid corticotropin content,
      different levels of corticotropin release after exogenous vasopressin, higher
      serum levels of progesterone, higher dehydroepiandrosterone: androstenedione
      ratio (during corticotropin therapy), a higher cerebrospinal fluid gamma
      aminobutyric acid content, and higher cerebrospinal fluid nerve growth factor
      concentrations. It remains to be seen whether the biochemical differences between
      the two groups are specific or only happen to correlate with the early brain
      damage. However, these differences would explain many pathophysiologic features
      of infantile spasms.

PMID- 8877607
TI  - Head circumference measurements in children with autism.
AB  - To assess head circumference in children with autism, 148 charts were
      retrospectively reviewed. All of the children met the Diagnostic and Statistical
      Manual of Mental Disorders (DSM-III or DSM-III-R) criteria for autism and had no
      known underlying condition that might affect head circumference. In addition,
      data were collected regarding height, weight, brain imaging, cognitive
      development, adaptive behavior, and language. The children were divided into two
      groups: those with head circumference at or above the 98th percentile (Group 1)
      and those with head circumference below the 98th percentile (Group 2). Group 1
      consisted of 27 (18.2%) of the children. Height measurements were significantly
      higher in Group 1 as compared with Group 2 (P = .0006) as were weight
      measurements (P = .0003). Group 1 had a significantly lower percentage of females
      (P = .04) and lower adaptive behavior scores (P = .0067) than Group 2. Routine
      brain imaging studies could not explain the macrocephaly in Group 1. The etiology
      of large head circumference and increased growth indices in children with autism
      is unclear.

PMID- 8877608
TI  - Child neurology--from my point of view.
AB  - My own way to pediatric neurology started with basic training in pediatrics at a
      time when neurology barely existed, but certainly not pediatric neurology. By
      chance, I happened to be involved with a family with interesting muscular
      symptoms and this awoke my interest in neurology in general, and particularly in
      muscle diseases and genetically determined diseases. I am deeply indebted to
      American pediatric neurology, since I got a wonderful chance to study pediatric
      neurology in the United States, particularly in Boston. To work within this field
      has always given me pleasure. The combination of strictly logical neurologic
      reasoning and the way to reach it through improvising and playing with the child
      is particularly exciting. For many of these diseases we have no definite cure,
      and some of them cause the death of the child, a serious situation for all
      involved. In these situations, I have come to know many parents for whom I feel a
      deep respect, affection, and admiration. Children and parents have taught me
      much, particularly the necessity of always being at eye level with the patient or
      the conversation partner, both literally and figuratively.

PMID- 8877609
TI  - Axonal neuropathy with perineurial hyperplasia: report of a case with multifocal
      involvement.

PMID- 8877610
TI  - Primary primitive neuroectodermal tumor of the leptomeninges.

PMID- 8877611
TI  - Congenital Guillain-Barre syndrome.

PMID- 8877612
TI  - Neurocutaneous melanosis with Dandy-Walker malformation complicated by primary
      spinal leptomeningeal melanoma.

PMID- 8877613
TI  - Macrocephaly, subarachnoid fluid collection, and glutaric aciduria type I.

PMID- 8877614
TI  - Respiratory chain dysfunction in progressive neuronal degeneration of childhood
      with liver disease.

PMID- 8877615
TI  - Stroke in children after blunt intraoral trauma: use of magnetic resonance
      angiography as a noninvasive diagnostic tool.

PMID- 8877616
TI  - Pyridoxine-dependent epilepsy: the need for repeated pyridoxine trials and the
      risk of severe electrocerebral suppression with intravenous pyridoxine infusion.

PMID- 8877617
TI  - Working memory and supervisory control after severe closed-head injury. A study
      of dual task performance and random generation.
AB  - Survivors of severe closed-head injury (CHI) frequently suffer from slowed
      information processing. Whether supervisory strategies are additionally impaired
      remains a point of debate. The first part of this study employed a self-paced
      dual task; the second part, a random generation task, performed at a paced rate,
      under single and dual task conditions. A measure of information processing speed
      was used as a covariate in statistical analysis. In the first experiment, in
      addition to slow processing, patients performed slightly poorer than controls on
      each task. In the second experiment, patients' performance (one randomness index
      in single task condition, and processing of dual task) was impaired even after
      statistical control of slow processing. These results suggest that there is at
      least some degree of impairment in supervisory strategies in addition to, but
      independent of, slowed processing. The clinical significance of this finding is
      discussed.

PMID- 8877618
TI  - Discriminability of the Wisconsin Card Sorting Test using the standardization
      sample.
AB  - The four neurological patient groups and the normals from the Wisconsin Card
      Sorting Test (WCST) standardization sample were used to examine the
      discriminability of the WCST's indices. Results reveal consistent differentiation
      of normals from the patient groups on all WCST variables, with classification
      rates averaging 71% accuracy. However, patient groups with frontal, diffuse, and
      nonfrontal lesions were not consistently discriminable from each other. The
      results suggest that the WCST is most usefully conceptualized as a measure of
      executive abilities that involves the frontal lobes, but should not be considered
      solely as a marker of isolated frontal lobe pathology.

PMID- 8877619
TI  - Sustained attention in untreated non-PKU-hyperphenylalaninemia.
AB  - Twenty-four untreated adolescent and adult patients with non-PKU
      hyperphenylalaninemia (HPA) (serum Phe levels < 600 mumol/L) and 24 healthy
      controls matched for age, sex, and IQ were investigated for simple motor reaction
      time and sustained attention, which are prolonged in patients with mild or
      classical phenylketonuria (PKU). Patients with HPA were of normal intelligence
      and did not differ significantly from healthy controls in their test results. For
      HPA patients, reaction times and sustained attention were not significantly
      influenced by serum phenylalanine concentrations. We conclude that dietary
      treatment is not necessary in patients with non-PKU HPA.

PMID- 8877620
TI  - Neuropsychological subgroups of patients with Alzheimer's disease.
AB  - Neuropsychological data from 134 patients diagnosed with probable Alzheimer's
      disease (AD) were studied retrospectively to investigate whether subgroups of
      patients with qualitatively distinct profiles could be identified. Three
      empirical classification approaches were undertaken in this regard: Q-type factor
      analysis, hierarchical agglomerative cluster analysis, and iterative
      partitioning. Three subgroups were consistently identified across the clustering
      methods. Subgroup 1, the largest of the groups, was marked by moderate to severe
      anomia and constructional dyspraxia. Individuals in subgroup 2 displayed
      relatively spared visual-perceptual/constructional functioning but severe anomia.
      Members of subgroup 3 exhibited intact naming and nonverbal reasoning and
      moderate difficulty in copying overlapping figures. The three subgroups did not
      differ with respect to age, age at disease onset, duration of illness,
      educational level, or Hamilton depression rating. Detailed description of the
      data analyses are provided as a tutorial outlining subtyping methodology. Results
      are discussed in terms of the subgroup and the stage model approaches to the
      conceptualization of AD.

PMID- 8877621
TI  - Automatic semantic facilitation in Alzheimer's disease.
AB  - To explore the nature of semantic deficit in Alzheimer's disease patients (AD
      patients) we compared two tasks that are known to be very different with respect
      to the type of attentional demand and conscious effort they require: lexical
      decision (automatic) in a semantic priming paradigm and semantic relatedness
      judgements (intentional). In order to minimise post-lexical facilitation we
      devised a semantic priming experiment that met an automatic condition as much as
      possible, and we selected patients without severe word recognition deficits. AD
      patients showed reduced accuracy in the semantic relatedness judgements as
      compared to controls. Some effect of priming was found, but this was weaker than
      in normals. AD patients also differed from controls on targets preceded by a
      nonlinguistic prime (neutral condition) where their reaction times were slower as
      compared to neutral condition.

PMID- 8877622
TI  - Recovery of speed of information processing in closed-head-injury patients.
AB  - After severe traumatic brain injury, patients almost invariably demonstrate a
      slowing of reaction time, reflecting a slowing of central information processing.
      Methodological problems associated with the traditional method for the analysis
      of longitudinal data (MANOVA) severely complicate studies on cognitive recovery.
      It is argued that multilevel models are often better suited for the analysis of
      improvement over time in clinical settings. Multilevel models take into account
      individual differences in both overall performance level and recovery. These
      models enable individual predictions for the recovery of speed of information
      processing. Recovery is modelled in a group of closed-head-injury patients (N =
      24). Recovery was predicted by age and severity of injury, as indicated by coma
      duration. Over a period up to 44 months post trauma, reaction times were found to
      decrease faster for patients with longer coma duration.

PMID- 8877623
TI  - Adult sensory capacities as a function of birth risk factors.
AB  - This study examined the relationship between birth risk factors and sensory
      capacity in 1245 young adults (mean age = 19.9 years). Nine birth risk factors
      were included (long labour, breech birth, breathing difficulty, instrument
      delivery, Caesarian delivery, multiple birth, premature birth, low birth weight,
      and high-risk birth order) and six sensory capacities were tested (Snellen visual
      acuity, stereopsis, color discrimination, pure-tone hearing, speech recognition,
      and sound localization). Mild birth stressors were strongly predictive of reduced
      visual acuity and stereoscopic discrimination, and mildly predictive for the
      other sensory measures. The fact that vision was more vulnerable to the effects
      of birth stress than audition may be due to the slower maturation of the visual
      system. Of the birth stressors examined, twinning was found to have the largest
      effect on sensory function, possibly because it often occurs conjointly with
      other birth stressors such as low birth weight, breech presentation, and
      breathing difficulty and may involve the use of birthing instruments such as
      forceps.

PMID- 8877624
TI  - Cognitive slowing in patients with acquired brain damage: an experimental
      approach.
AB  - Nine brain-damaged patients (19-54 years old) with "cognitive slowing", and 10
      healthy subjects (26-56 years old) were tested with a slightly modified version
      of a Sternberg memory task (varied-set procedure). Cognitive slowing in the sense
      of reduced information-processing speed is reflected by mean RTs and slopes and
      intercepts derived from the RTs as a function of memory set size. Patients showed
      a marked increase of these parameters. While the results obtained from the
      control subjects are in accordance with typical Sternberg findings, patients
      showed no parallel regression lines for positive and negative responses. As an
      alternative explanation for this result an extended "self-terminating" process is
      proposed that also appears to be helpful in explaining the overall cognitive
      slowing in the patients.

PMID- 8877625
TI  - Performance of healthy subjects and patients with resection from the anterior
      temporal lobe on matched tests of verbal and visuoperceptual learning.
AB  - We examined the equivalence of three matched forms of the Rey Auditory Verbal
      Learning Test (RAVLT) and three parallel forms of a new nonverbal analog, the
      Aggie Figures Learning Test (AFLT). One hundred and fourteen healthy subjects,
      primarily college students, were administered corresponding forms of the two
      tasks. For both tasks the three forms proved to be well-matched; as well, overall
      performance on the RAVLT was comparable to that on the AFLT. The two tasks were
      also administered to 23 patients with anterior resection from the left or right
      temporal lobe (ATL). Findings showed that right ATL patients were significantly
      impaired on the learning trials of the AFLT as compared to their learning on the
      RAVLT; they showed little forgetting of figures or words over a 20-min delay
      interval. By contrast, left ATL patients showed severe forgetting of words as
      compared to figures, but their learning curve for the RAVLT did not differ from
      that on the AFLT.

PMID- 8877627
TI  - Brainstem thrombosis: patient's viewpoint 12 months post stroke.
AB  - A patient who sustained brainstem thrombosis provides feedback on hospital care.
      Twelve months post trauma, the patient discusses the important role of hospital
      staff and visitors in his recovery and provides helpful feedback to all care
      givers.

PMID- 8877626
TI  - Actual versus self-reported cognitive dysfunction in HIV-1 infection: memory
      metamemory dissociations.
AB  - The relationship between subjective awareness and objective neuropsychological
      status in HIV-1 infection remains unclear. Forty-six HIV-1 seropositive males
      were administered a battery of neuropsychological measures assessing episodic
      memory, metacognition, and depression. Results of ANOVA revealed a dissociation
      between subjects' self-complaint of neuropsychological impairment and objective
      performance, with subjects who denied cognitive impairment performing worse on
      memory testing. Three subgroups were identified: A group whose self-reported
      cognitive impairment exceeded deficits demonstrated on memory testing (37% of
      subjects); a group who denied impairment but evidenced deficits on memory testing
      (26% of subjects); and a group whose self-appraisal was consistent with
      performance (37% of subjects). These data suggest that self-report of cognitive
      dysfunction among HIV-1 infected subjects is frequently at variance with
      objective neuropsychological testing and that diminished awareness of decline
      among medically symptomatic HIV-1 infected subjects can be identified.

PMID- 8877628
TI  - Application of psychometric standards to scoring system evaluation: is "new"
      necessarily "improved"?
AB  - Psychometric guidelines are suggested that expand the evaluation of scoring
      systems beyond the most frequently (and often singly) considered criterion, that
      of interrater reliability. Principles of reliability and validity are elaborated
      and discussed with regard to scoring systems. Also addressed are assays for
      efficiency in applying a new system, the effects of rater proficiency on outcome
      scores, the comparison of costs and benefits of new scoring systems, and the
      comparison of a new scoring system to an existing system to demonstrate its
      advantage. As a timely example to illustrate these principles, a new scoring
      system is introduced for the Rey-Osterrieth Complex Figure Test and is compared
      to the most popular scoring system for this test (Lezak, 1983, p. 400). The
      proposed principles would be relevant to any scoring system that codes subjective
      behavioral data into objective values.

PMID- 8877629
TI  - Development and validation of a demographic correction system for
      neuropsychological measures used in the Canadian Study of Health and Aging.

PMID- 8877630
TI  - Barrett's esophagus and adenocarcinoma. The need for a consensus conference.
AB  - The fear of cancer has evoked calls for intensive surveillance programs in
      Barrett's esophagus. Two evolving issues are fueling this fire: (a) the rising
      risk of adenocarcinoma of the esophagus over the past 20 years and (b) the
      coincidental increase in the recognized prevalence of Barrett's esophagus in the
      general population. However, these sobering statistics must be carefully weighed
      against the lack of adverse effects on survival and the cost of an extensive
      surveillance program for adenocarcinoma in Barrett's esophagus, the latter
      estimated at between $(300) and $(1,500) million per year. Barrett's esophagus
      and its associated cancer risk represent a crisis in gastroenterology. A
      consensus conference of leading basic and clinical scientists is needed in this
      area.

PMID- 8877631
TI  - The demise of modern medicine and gastroenterology.
AB  - A country that once led technological development in health care now leads the
      charge back to the cave, from which it took mankind 2 million years to emerge.
      The problems in U.S. health care are not simple. Therefore, there are no simple
      solutions. True health-care reform can be accomplished only via improved and
      unbiased public education, identification of the role for primary care, and the
      need for sub- and sub-subspecialties. Government has an important role, but even
      more importantly, as a nation, our priorities for rewards require careful
      reevaluation. Suppliers and consumers must sit down at the same table, realizing
      that basic health care is not responsive to the usual supply and demand theories
      proposed by economists. Only then can health care reform be considered a positive
      change.

PMID- 8877632
TI  - Is there health in wellness?
AB  - In the last 20 years, patient autonomy has vastly increased and a "well-being"
      movement has flourished, with great benefits but with definite drawbacks as well.
      Exaggeration of the individual's potential for prevention and self-healing can
      foster a crude psychological reductionism that hampers potential for subtle
      etiologic understanding and may weaken research, as well as creating a tendency
      to blame the victim. Probing of the health effects of any activity before
      engaging in it can lead to healthier-than-thouness and a fear of living. The well
      being movement tends to ignore social causes of disease in favor of individual
      ones and therefore to disregard a need for social remedies. Both theory and
      practice can be contaminated by economic motives: Medicine is expensive,
      meditation is cheap. The chasm between the "mind-body" school and the dominant
      medical model may have widened as some holistically minded individuals, finding a
      haven in the well-being movement, give up on affecting the medical mainstream.
      Thus, the advance of holistic medicine has aided in conceptualizing the health
      illness continuum, in understanding pathogenesis, and in discovering new
      preventive and therapeutic tools, but its emphasis on internal causes and
      therapies should not be allowed to detract resources from the equally important
      ones lying outside the realm of lifestyle.

PMID- 8877633
TI  - Sclerotherapy in bleeding gastric varices of hepatic schistosomiasis.
AB  - We report the results of sclerotherapy in 20 patients with bleeding gastric
      varices due to hepatic schistosomiasis. In an endemic area, patients with hepatic
      schistosomiasis, and bleeding gastric varices seen on endoscopy to be inferior
      extension of esophageal varices, were treated with emergency endoscopic injection
      just proximal to the cardia. Hemostasis was achieved in 17. Obliteration of
      varices was achieved in all patients with sclerotherapy, combined with surgery.
      Thirteen patients who had not been operated on in the past and consented to
      surgery underwent esophagogastric devascularization with splenectomy. Surgery was
      carried out as an emergency in the three patients who did not respond to
      sclerotherapy and electively in 10 patients after control of bleeding. After
      surgery, sclerotherapy was required for remnant varices. One patient with Child
      Pugh grade C cirrhosis died of hepatic encephalopathy after control of the bleed.
      During a median follow-up of 9 months (range, 1-25 months), recurrence of
      bleeding in one patient and recurrent varices in two others were controlled with
      sclerotherapy. One patient had a fatal hemorrhage at home. We conclude that
      sclerotherapy effectively controls acutely bleeding type 1 gastric varices.
      Combined with esophagogastric devascularization and splenectomy, long-term
      results may be encouraging in patients with hepatic schistosomiasis.

PMID- 8877635
TI  - Increased incidence of proximal colon cancer in the elderly.
AB  - To define the characteristics of colorectal cancer with regard to site
      distribution, age, and sex, due to the significantly increased incidence of
      colorectal cancer in Japan, we investigated 1,205 Japanese patients with
      colorectal cancer between 1975 and 1994. When we compared site distribution for
      age and sex in the entire 20-year period, tumors in the proximal colon were more
      frequent in elderly patients than in young ones (p < 0.05); this tendency was
      true only for females (p < 0.01), but not for males. The increased incidence of
      proximal colon cancer in elderly patients was also found in the second 10-year
      period (p < 0.05). Because elderly patients are characterized by an increasingly
      high incidence of proximal colon cancer in recent years, more concerted efforts
      for the early detection of proximal colon cancer, particularly in the elderly,
      are called for.

PMID- 8877634
TI  - Reliability of immunologic markers of celiac sprue in the assessment of mucosal
      recovery after gluten withdrawal.
AB  - We studied 47 adults (21 men, 26 women), with biopsy-proven celiac sprue and anti
      endomysin antibody (EmA) positivity while untreated, to evaluate the usefulness
      of both serologic markers of celiac sprue [i.e., immunoglobulin A (IgA)-EmA and
      total Ig-anti-gliadin (AGA) antibodies] and of a detailed dietary inquiry in
      predicting the mucosal pattern after gluten withdrawal. A second biopsy was
      repeated 8-30 months after beginning a gluten-free diet, along with EmA and AGA
      determinations and the dietary inquiry. Both EmA and AGA were appraised by
      indirect immunofluorescence on monkey esophagus and rat kidney, respectively.
      Intestinal biopsy was graded according to Cooke's criteria. After gluten
      withdrawal, intestinal mucosa reverted to normal in only nine patients. Both EmA
      and AGA showed high positive but low negative predictive values on intestinal
      histologic outcome. The positive predictive value of admission of dietary lapses
      was 100%, whereas the negative predictive value was 39.1%. Neither serologic
      markers nor dietary inquiries are to be regarded as reliable predictors of
      intestinal outcome after a gluten-free diet. Biopsy remains the best means of
      ascertaining mucosal recovery.

PMID- 8877636
TI  - Primary pancreatic non-Hodgkin's lymphomas.
AB  - Primary pancreatic lymphomas are rare. We reviewed our experience at King Faisal
      Specialist Hospital and Research Center; the hospital tumor registry identified
      five patients with primary pancreatic lymphoma among the 1,212 adult non
      Hodgkin's (NHL) cases referred to this institute during 1987-1994. The histology
      was diffuse large cell in all cases. According to the Ann Arbor classification,
      four patients had stage IE and one patient stage IIE disease. The diagnosis was
      established by laparotomy in three and ultrasound or CT-guided biopsy in two
      patients. All patients received chemotherapy. Radiotherapy was used in two cases;
      in one patient the pancreatic bed was irradiated, whereas in the other radiation
      was given for obstructive jaundice. Four patients are alive with no evidence of
      disease at 84, 26, 24, and 21 months follow-up. One patient relapsed at 12 months
      following chemotherapy and is alive with disease at 23 months follow-up. The
      clinical and radiological findings in primary pancreatic NHL are not
      pathognomonic, and the diagnosis is only established on histopathological
      examination. The management should be nonsurgical as the response to chemotherapy
      and radiation appears to be no different from NHL at other sites.

PMID- 8877637
TI  - Correlation of liver density by magnetic resonance imaging and hepatic iron
      levels. A noninvasive means to exclude homozygous hemochromatosis.
AB  - The diagnosis of hemochromatosis requires liver biopsy and the quantification of
      hepatic iron. Magnetic resonance imaging (MRI) of the liver shows a
      characteristic decrease in tissue signal intensity in iron overload states, but
      its role in the diagnosis of hemochromatosis has not been fully delineated. Forty
      three patients (31 men and 12 women) were referred for the evaluation of
      hemochromatosis based upon a fasting transferrin saturation > 55% and/or a serum
      ferritin > 400 ng/ml in males or > 300 ng/ml in females. Each patient
      prospectively underwent MRI of the liver prior to percutaneous liver biopsy and
      quantitative hepatic iron determination. Homozygous hemochromatosis was diagnosed
      in 10 patients based upon an hepatic iron/age index > or = 2. MRI was performed
      with a 1.5 Tesla system using standard spin-echo sequences (T1; TR = 300-500 ms,
      TE = 13-17 ms, PD; TR = 2,000-2,600 ms, TE = 30 ms). Signal intensity values were
      blindly determined for regions of interest in liver and skeletal muscle at T1 and
      proton density. Ratios of liver to muscle (LM) for T1 and proton density (PD)
      calculated from these values showed a significant correlation with quantitative
      iron by multiple regression analysis. The LMPD ratio provided the best
      correlation with hepatic iron (r = -0.6946; p < 0.001). Linear regression
      analysis also provides an equation that can be used to predict hepatic iron based
      upon the LMPD ratio; micrograms/g of hepatic iron = (-5,174 x LMPD) + 9,932. All
      patients with LMPD ratios of > 0.5 had hepatic iron/age indices of < 2.0, thereby
      excluding homozygous hemochromatosis. These results suggest that LMPD ratios
      derived from MRI of the liver can accurately predict hepatic iron content. These
      ratios can be clinically useful in the evaluation of hemochromatosis among
      patients who either refuse or have contraindications to liver biopsy.

PMID- 8877638
TI  - Tuberculous esophagocutaneous fistula.
AB  - Esophagocutaneous fistula due to tuberculosis is a distinctly rare entity, with
      only two cases reported over the past 25 years. We report this unusual
      complication in an 85-year-old, human immunodeficiency virus-negative man and
      review the relevant literature.

PMID- 8877639
TI  - Polymyositis, alopecia universalis, and primary sclerosing cholangitis in a
      patient with Crohn's disease.
AB  - We report a 36-year-old man with Crohn's disease, primary sclerosing cholangitis,
      and alopecia universalis. Six years after the onset of intestinal disease, the
      patient developed severe muscular pain and weakness of the neck. Muscle biopsy
      revealed myositis. Immunosuppressive treatment led to a significant improvement
      of muscular symptoms. Myositis in inflammatory bowel disease appears to be an
      important differential diagnosis in corticoid myopathy. Both alopecia and
      polymyositis are rarely associated with inflammatory bowel disease; thus, they
      have to be discussed as extraintestinal manifestations.

PMID- 8877640
TI  - Endoscopic management of a bronchobiliary fistula.
AB  - A bronchobiliary fistula is a rare entity that manifests as bilioptysis. We
      report a 73-year-old woman with a hepato-cellular carcinoma who developed a
      bronchobiliary fistula. Endoscopic biliary sphincterotomy and insertion of a
      prosthesis led to successful resolution of symptoms and restoration of normal
      bile flow. We review the pertinent literature and the basis for management.

PMID- 8877641
TI  - Resected sigmoid carcinoma with 13-year metastasis-free interval. Sternal
      recurrence detected by immunoscintigraphy.
AB  - Colorectal cancers rarely present with bone metastases. Regular postoperative
      monitoring after resection by conventional imaging techniques and
      carcinoembryonic antigen levels aids physicians in identifying such tumor
      recurrences. However, some recurrences might elude detection by bone scan,
      computed tomography, and magnetic resonance imaging, and newer tests such as
      immunoscintigraphy using radioimmune-tagged monoclonal antibodies may be more
      diagnostic. Here we report a case, presenting with delayed recurrence at a rare
      bony site, in which application of immunoscintigraphy helped in the definitive
      detection of the tumor recurrence.

PMID- 8877642
TI  - Primary hepatic leiomyosarcoma.
AB  - Hepatomegaly was noted in a 63-year-old man who presented with an exacerbation of
      chronic pulmonary disease. A diagnosis of hepatic leiomyosarcoma was made by fine
      needle aspiration biopsy. Intensive investigations failed to reveal a primary
      source. The patient was treated conservatively.

PMID- 8877643
TI  - Hepatic amyloidosis presenting with severe intrahepatic cholestasis.
AB  - Systemic amyloidosis presenting with jaundice is rare. A case of primary
      amyloidosis presenting with severe intrahepatic cholestasis is reported. The
      patient had hepatomegaly, ascites, and a markedly elevated serum alkaline
      phosphatase level. He had a rapid downhill course resulting in death. Autopsy
      showed evidence of amyloidosis involving multiple organs, including the liver,
      kidney, and heart.

PMID- 8877644
TI  - Intrahepatic cholestasis without hepatitis induced by amoxycillin/clavulanic
      acid.
AB  - Amoxycillin/clavulanic acid liver injury is very rare. We describe an exceptional
      case of intrahepatic cholestasis without hepatitis induced by
      amoxycillin/clavulanic acid. Recognition of this benign cholestatic syndrome as a
      side-effect may obviate unnecessary complementary and costly procedures.

PMID- 8877645
TI  - Jejunal angiodysplasia confirmed by intravascular injection technique in vitro.
      Report of a case and review of the literature.
AB  - Angiodysplasia of the small intestine is a rare but important cause of
      gastrointestinal bleeding. We present a 64-year-old man with repeated melena in
      whom the diagnosis of multiple angiodysplasia of the jejunum was suggested by
      angiography. The affected segment of the small intestine, in which reddish
      patches were detected by intraoperative endoscopy, was removed. The combined
      technique of injecting a dye and a water-soluble contrast medium into the
      resected specimen revealed areas of dilated vessels, which were diagnosed
      histologically as angiodysplasia. This case suggests that angiodysplasia of the
      small intestine can be recognized clinically before the operation and that the
      intravascular injection technique is useful in confirming the diagnosis in the
      resected specimen in vitro. We describe this case in detail and review other
      cases of small intestinal angiodysplasia reported in the English literature.

PMID- 8877646
TI  - Adenocarcinoid of the liver arising within an area of hamartoma with predominant
      bile duct component.
AB  - Malignant transformation in bile duct hamartomas has been previously reported in
      very rare instances. Here, we describe a unique case of a neuroendocrine tumor of
      the liver arising within an area of unusually large hamartoma with predominant
      bile duct component, hitherto unreported and distinct from the conventional von
      Meyenburg complex. The tumor was apparently secreting gastrin and chromogranin,
      with associated gastrinoma syndrome over several years. The histologic picture
      was reminiscent of a moderately differentiated adenocarcinoid, with positive
      mucin staining in a signet ring pattern. Tumor cells showed positive staining for
      neuron-specific enolase, chromogranin A, gastrin, and serotonin. Staining for
      pancreatic hormone peptides was negative. Resection of the tumor was apparently
      curative, with complete resolution of the patient's symptoms.

PMID- 8877647
TI  - Intrahepatic biliary endoscopy in sclerosing cholangitis.
AB  - Sclerosing cholangitis is usually diagnosed by clinical findings coupled with
      radiographic imaging of the bile ducts by ERCP. Direct imaging of both the intra-
      and extrahepatic biliary tree provides an opportunity to further study this
      disorder and its potential complications such as biliary malignancy. However,
      endoscopic visualization of the intrahepatic bile ducts in sclerosing cholangitis
      is potentially limited by the size of available cholangioscopes and the presence
      of strictures. Below, we report our initial results using a 0.8-mm fiberoptic
      endoscope placed through a partially steerable 1.8-mm guide catheter. The system
      allows visualization of the intrahepatic biliary tree beyond areas of stricture
      in the more distal ducts.

PMID- 8877648
TI  - Helicobacter pylori eradication helps resolve pyloric and duodenal stenosis.

PMID- 8877649
TI  - Prevalence of polypoid lesions of the gallbladder in urban and rural areas of
      Japan: comparison between 1988 and 1993.

PMID- 8877650
TI  - Carcinoid of the ampulla of Vater: dealing with a medical curiosity.

PMID- 8877651
TI  - Acute eosinophilic pneumonia associated with ranitidine.

PMID- 8877652
TI  - A pilot study of thymosin-alpha 1 therapy for chronic hepatitis D.

PMID- 8877653
TI  - Vermiform appendix sealing sigmoid colon perforation.

PMID- 8877654
TI  - Hepatitis associated with varicella infection in an immunocompetent adult.

PMID- 8877655
TI  - Evaluation of the long-term efficacy and safety of locally-applied minocycline in
      adult periodontitis patients.
AB  - The objectives of the present study were to establish in a long-term
      investigation the safety as well as the clinical and microbiological efficacy of
      scaling and rootplaning combined with local application of 2% minocycline
      hydrochloride-gel versus placebo-gel in patients with moderate to severe chronic
      adult periodontitis. This was an 18 months, randomized, double-blind, parallel,
      comparative study, in which 20 healthy patients with moderate to severe chronic
      periodontitis participated. At baseline, all patients received professional oral
      hygiene-instruction and supra- and subgingival scaling and root planing. The
      minocycline-gel was applied subgingivally baseline, 2 weeks, 1, 3, 6, 9 and 12
      months. Microbiological evaluation was carried out using DMDx to identify the
      following bacteria: Porphyromonas gingivalis, Prevotella intermedia,
      Actinobacillus actinomycetemcomitans, Campylobacter rectus, Fusobacterium
      nucleatum and Treponema denticola. In addition standard microbiological
      techniques were used for the detection of P. gingivalis, P. intermedia, P.
      micros, A. actinomycetemcomitans, C. rectus, F. nucleatum, C. albicans and
      Enterobacteriaceae. Results showed a statistically significant improvement for
      all clinical parameters irrespective of the treatment modality. No differences
      were observed between test and control with regard to probing depth and
      attachment level. The DMDx data showed a significant reduction in both the
      numbers and the prevalence over the 15 months period, but no significant
      difference between groups. Culture data showed that at baseline two-third were
      positive for P. gingivalis and P. intermedia. Analysis over the 18 month period
      showed no significant difference between the two treatment modalities. C.
      albicans and Enterobacteriaceae were detected only in small proportions at each
      time interval in a limited number of patients. No adverse reactions were observed
      during the trial period. The present patient group responded favourably to
      scaling and rootplaning, but did not benefit from an effect of local of
      minocycline. Subgingival debridement in combination with oral hygiene instruction
      by itself has been shown to be effective. It remains to be studied whether local
      application of minocycline can be effective as an adjunct to mechanical therapy
      in sites that respond poorly to conventional treatment.

PMID- 8877656
TI  - The importance of immunoglobulin-breakdown supporting the growth of bacteria in
      oral abscesses.
AB  - Oral bacteria play an important role in the causation of oro-facial abscesses.
      However, they can also be involved in brain, liver and lung abscesses. To
      persist, it is essential that these bacteria can grow on those sites. The main
      source of nutrients for growth in abscesses is likely to be tissue exudate, which
      is rich in serum-derived proteins, and relatively poor in free amino acids and
      carbohydrates. Degradation of intact proteins seems a crucial step in providing
      the peptides necessary for energy generation. The aim of this study was to
      investigate the capacity of microorganisms from asscesses to degrade serum
      proteins, in particular immunoglobulins. To this end, samples were taken by
      aspiration from 16 odontogenic abscesses. It was found that pus from abscesses
      differed strongly in the concentration of viable bacterial cells. The ability of
      the abscess microflora to degrade serum proteins was investigated after growth of
      the sample in heat-inactivated human serum. The microflora from abscesses with a
      high concentration (n = 10) of bacteria strongly degraded immunoglobulins,
      whereas breakdown of immunoglobulins was virtually absent after growth of the
      microflora from low-bacterial concentration (n = 6) abscesses. Bacteriological
      analyses revealed the presence of at least one proteinase-producing species, like
      Porphyromonas, black-pigmented Prevotella species, or Actinomyces meyeri, in
      abscesses with a high density of bacteria, but not in those with low bacterial
      density. The results indicate that the capacity to degrade intact proteins, in
      particular immunoglobulins, is a major determinant of bacterial growth in
      abscesses.

PMID- 8877657
TI  - Toothbrushing force in relation to plaque removal.
AB  - This was a 2-part study. The purpose of the 1st part was to examine the
      relationship between brushing force and plaque removal efficacy comparing a
      regular manual toothbrush (M) with an electric toothbrush the Braun/Oral-B Plak
      Control (B). The study consisted of a single oral prophylaxis followed by 5
      experiments which differed solely in respect to toothbrushing force. At baseline
      (after 24-h plaque accumulation), the amount of dental plaque was evaluated and
      subsequently, the subject's mouth was brushed by a dental hygienist. Brushing was
      carried out in a random split-mouth order. Either the 1st and 3rd quadrants or
      the 2nd and 4th quadrants were brushed with 1 toothbrush and the 2 remaining
      quadrants with the other. The available time for the brushing procedure was 2
      min. After brushing, the amount of remaining dental plaque was assessed. The
      force used in experiment 1 through 5 was 100, 150, 200, 250, 300 g, respectively.
      The results show that when brushing force is increased, more plaque is removed
      with either of the two brushes. Except for the high brushing force (300 g), the
      electric toothbrush removed more plaque than the manual brush. The purpose of the
      2nd part was to evaluate the habitual brushing force which individuals use with
      various toothbrushes. Besides a manual toothbrush (M), 3 electric toothbrushes
      were examined, the Rotadent (R), Interplak (I) and Braun (B). 20 subjects were
      selected on the basis of being 'good brushers' (plaque score at screening < 25%).
      At baseline, each subject randomly received 1 of the 4 brushes. They were allowed
      a training period of 3 weeks at the end of which they were asked to abstain from
      brushing for at least 24 h. The plaque (Turesky modification of the Quigley &
      Hein) was scored, after which the subjects brushed their teeth (2 min) with the
      assigned toothbrush equipped with a strain gauge. A computer set-up measured (100
      Hz) and calculated the mean brushing force. After brushing, the amount of
      remaining plaque was assessed. The design of the study was a 4-way cross-over.
      The results show that with a manual brush, considerably more force is used than
      with the electric brushes (R = 96, I = 119, B = 146, M = 273). No significant
      relation between brushing force and plaque removal was demonstrated for any of
      the brushes.

PMID- 8877658
TI  - Histopathologic alterations of periodontium in cyclosporin-treated rats. Is the
      periodontium a target tissue for the drug?
AB  - Gingival dimensions and histopathologic alterations in periodontium were examined
      in rats continuously exposed to cyclosporin-A (CSA). 60 male Sprague-Dawley rats
      were divided into 2 groups. Rats in the test group daily received CSA in mineral
      oil by gastric feeding at a dosage of 30 mg/kg body weight for 6 weeks. Rats in
      the control group received mineral oil only. 10 rats from each group were
      sacrificed at 2-week intervals. Gingival dimensions were assessed from stone
      models obtained from the maxillary and mandibular incisal regions. Horizontal,
      sagittal and frontal tissue sections were obtained from these regions as well.
      Gingival dimensions in the mandibular and maxillary incisal regions were
      significantly increased in rats exposed to CSA. Light-microscopic observations
      revealed a granulation tissue formation at tooth-gingiva interface and an
      irregular bony surface on dental alveoli in experimental animals. Because both
      soft and hard tissue of periodontium in experimental rats being significantly
      effected by CSA compared to control animals, we hypothesized that the
      periodontium is a target tissue for CSA.

PMID- 8877659
TI  - Evaluation of the frequency of HLA determinants in patients with gingival
      overgrowth induced by cyclosporine-A.
AB  - This study has been designed to investigate the immunogenetic susceptibility of
      Cyclosporine-A (CsA) immunosuppressed renal transplant patients to development of
      gingival overgrowth, and the amplifying effect of calcium channel blockers on the
      severity of this clinical entity. 52 renal transplant recipients were selected
      and initially grouped as follows: group (Gp)1: CsA (n = 7); Gp 2: CsA + verapamil
      (n = 26); Gp 3: CsA + diltiazem (n = 6); Gp 4: CsA + nifedipine (n = 13). These
      groups were not found to be significantly different in age, sex, plaque index
      (PlI), gingival index (GI), calculus index, periodontal probing depth, serum CsA
      level, or duration of CsA therapy (p > 0.05). No significant (p > 0.05) additive
      effect of the calcium channel blockers on the gingival overgrowth (GO) was
      assessed. The main group (n = 52) was evaluated for the correlations between the
      clinical and the pharmacological variables and the GO. GI (rs = 0.60) and the
      periodontal probing depth (rs = 0.71) were found to be moderately correlated with
      the GO. The patients were regrouped based on the severity of overgrowth and
      recognized as responders (n = 26) and nonresponders (n = 26). Age, sex, calculus
      index, serum CsA level, duration of the CsA therapy, were not statistically
      different among these groups (p > 0.05). PlI, GI, periodontal probing depth, and
      GO were significantly higher in the responder group (p > 0.05). Analysis of HLA
      distribution of the responders and the nonresponders and comparison with the
      controls (n = 3731) revealed that a statistically significant (p < 0.001)% of the
      nonresponders were positive for HLA-DR1. These data would indicate that an
      immunogenetic predisposition should be suspected in the pathogenesis of the
      entity, and that HLA-DR1 would have a protective role against gingival overgrowth
      induced by CsA.

PMID- 8877660
TI  - The relationship of gingival crevicular fluid short chain carboxylic acid
      concentration to gingival inflammation.
AB  - Short-chain carboxylic acids (SCCA; C < or = 5; e.g., lactic acid, propionic
      acid, butyric acid) are metabolic by-products of bacterial metabolism which
      accumulate in the gingival crevice, and exhibit significant biological activity,
      including the ability to alter gene expression. It has been hypothesized that
      among the activities of SCCAs are their ability to contribute to gingival
      inflammation. This concept complements the notion that specific periodontal
      pathogens are the causative agents of gingival inflammation. To begin testing
      these 2 hypotheses, we examined the relationship between SCCA concentrations,
      specific putative periodontal pathogens, and gingival inflammation in medically
      healthy periodontally diseased subjects. We reasoned that if SCCAs and/or
      specific periodontal pathogens were causative gingival inflammatory agents,
      gingival inflammation should increase with increasing concentration of the
      inflammatory mediator. We also recognized that other clinical variables needed to
      be controlled for, and an objective quantitative assessment of gingival
      inflammation used. To accomplish these tasks, sites within subjects were
      stratified by location and pocket depth, and the following quantified: bacterial
      presence; SCCA concentration; and gingival inflammation. The results indicated
      that gingival inflammation directly and significantly correlated with SCCA
      concentrations in the maxillary and mandibular molars, incisors and canines (all
      r > or = 0.47; all p < or = 0.015; too few bicuspids were available for complete
      analysis). The relationship between gingival inflammation and SCCA concentration
      was best described by a natural log relationship. Gingival inflammation did not,
      however, correlate positively with either the total number of specific putative
      periodontal pathogens, or the sum of subsets of these pathogens (-0.31 < or = r <
      or = 0.39; 0.08 < or = p < or = 0.75) for any of the locations. Finally, the SCCA
      concentration did not correlate with the level of individual or groups of
      pathogens. These data, together with historical work and other preliminary data,
      support the hypothesis that SCCA, rather than specific putative periodontal
      pathogens, may be a causative agent in gingival inflammation. This work may, in
      part, begin to explain the apparent lack of a direct relationship between current
      gingival inflammation and the prediction of bacterially mediated periodontal
      attachment loss.

PMID- 8877661
TI  - Transient effect of a short-term educational programme without prophylaxis on
      control of plaque and gingival inflammation in school children.
AB  - The development of chronic inflammatory periodontal diseases is strongly
      correlated with the growth and maturation of subgingival bacterial colonies.
      Consequently a major preventive goal should be the control of plaque formation.
      We conducted a randomized, controlled trial to examine the short-term effect of
      an intensive instructional program without professional prophylaxis on the
      gingival health of 240, 11-14 year old school children. Plaque index (PlI),
      gingival index (GI), bleeding index (BI) and probing pocket depth (PD) were
      examined 4 x by 1 examiner blinded to the instruction. During the period of
      instruction, subjects in the experimental groups were involved in a plaque and
      gingivitis prevention program provided in separate educational sessions. One of
      the experimental groups (E-1; n = 80) was provided with a new toothbrush,
      toothpaste and instruction while the second experimental group (E-2; n = 80) was
      provided with toothbrush, toothpaste, dental floss and instruction. In the
      control group (C; n = 80) only dental examinations were provided: no preventive
      program or oral health measures were conducted. Examinations were conducted every
      3 months during the instructional period and at 6 months following the completion
      of the active preventive programme. During the experimental period there was a
      significant decrease (p < 0.001) in the mean PlI, GI and BI of the experimental
      groups following the program while in controls there was a slight but not
      significant increase of mean values (p > 0.05). During the preventive program
      experimental groups exhibited small but not significant (p > 0.05) reductions of
      PD. Experimental group 1 showed similar PlI, GI, BI and PD scores as experimental
      group 2 during the study. After the instructional program was completed and a
      period of 6 months had passed, there was a large and significant (p < 0.001)
      increase of mean PlI, GI and BI scores in both experimental groups back to the
      baseline levels. We conclude that a short-term preventative program without
      professional instrumentation induces a transient improvement of gingival health
      of schoolchildren but only during the instructional period. The maintenance of
      improved gingival health over longer time periods requires prolonged, repeated
      instruction by professionals. These measures may be difficult to institute and
      are of questionable cost-effectiveness.

PMID- 8877662
TI  - A clinical survey of periodontal conditions in Greece.
AB  - The present study used full-mouth clinical assessments of plaque, calculus,
      bleeding on probing, probing pocket depth and probing attachment level to
      evaluate the periodontal conditions in a rural (A) and an urban (B) sample of 25
      64 year old Greek adults, comprising 190 and 373 subjects, respectively. 13% of
      the subjects in sample (A) and 8% in sample (B) were edentulous, while mean
      values of teeth present in the four age cohorts ranged between 19.8-12.6 and 23.3
      18.3, respectively. A poor level of oral hygiene was recorded in both samples
      with high plaque, calculus and bleeding scores. Deep pocketing was more
      pronounced in the rural than in the urban sample; between 1.7 and 8.0% of all
      sites probed showed a PPD of > or = 6 mm and between 20 and 51.2% of the subjects
      in each age cohort had at least one deep pocket. Corresponding figures for the
      urban sample was 0.6-4.7% and 15.1-49.2%. However, the prevalence of severe
      attachment loss was of comparable magnitude in both samples; between 2.8-25.7% of
      the sites in sample (A) and 2.8-20.6% in sample (B) displayed a PAL of > or = 6
      mm, while 32.5-72.1% and 31.8-73.8% of the subjects, respectively, had at least
      one severely affected site. It was further found that the distribution of
      advanced disease in the samples was skewed; 14.4% of the subjects in sample (A)
      and 9.5% in sample (B) accounted for 75% of all deep pockets, while 21.8 and
      19.4% of the subjects, respectively, accounted for 75% of all sites with PAL of >
      or = 6 mm. Multiple regression revealed that male sex and high plaque and
      bleeding scores had a significant, positive influence to the amount of attachment
      loss on a subject level.

PMID- 8877663
TI  - Partial expression of the Papillon-Lefevre syndrome in 2 unrelated families.
AB  - The Papillon-Lefevre syndrome (PLS) is a rare, autosomal recessive trait that is
      characterized by palmar plantar keratosis (PPK) and severe, early onset
      periodontitis, affecting both deciduous and permanent dentitions. The clinical
      presentation of PLS is variable; the disease occurs so infrequently as to limit
      clinical cases for study. The exception is a few families with extensive
      consanguinity in which numerous cases occur. Of particular interest to mapping
      the genetic origin of the syndrome is the co-expression of the major traits of
      hyperkeratosis and periodontitis, and their severity. In this paper, we report 2
      families with multiple affected individuals from geographically remote areas. A
      large extended family, from the Cochin region of India, currently residing in
      Israel, in which there is documented consanguinity and a family from the
      southwest region of Germany. In each family, 1 individual presents with
      hyperkeratotic lesions with the complete absence of periodontal lesions. Further,
      the difference in severity of the hyperkeratotic lesions between families is
      marked, and one sibling in the German family expressed rapid, early onset
      periodontitis in the absence of PPK. The genetic nature and penetrance of the
      genetic defect are discussed.

PMID- 8877664
TI  - Increased gingival dimensions. A significant factor for successful outcome of
      root coverage procedures? A 2-year prospective clinical study.
AB  - The aim of this study was to evaluate whether an increased thickness of the
      gingiva through the use of a free connective tissue graft, in conjunction with a
      coronally advanced flap procedure, may positively influence the treatment outcome
      with respect to (i) root coverage and (ii) long-term stability of the position of
      the soft tissue margin following treatment of recession type defects. 67
      consecutive patients having a total of 103 buccally located recession type
      defects of at least 3 mm were included in the study. After an initial phase of
      prophylaxis including instructions in a tooth brushing technique giving minimal
      apically directed forces to the gingival margin, the recession sites were
      surgically covered with a coronally advanced flap alone (control sites), or
      coronally advanced flap combined with a free connective tissue graft taken from
      the palate (test sites). Clinical examinations, including assessments of oral
      hygiene, gingival conditions, recession depth, gingival height, probing pocket
      depth and probing attachment loss, were performed before and 6, 12 and 24 months
      after surgical treatment. The mean initial recession depth for both treatment
      groups was about 4.0 mm (SD 1.0) with a gingival height apical to the recession
      of 1.0 mm (0.5). At the re-examination performed 6 months after surgical
      treatment, the mean recession depth had decreased to 0.2 mm in both the test and
      control groups. Complete root coverage was observed at 72% of the test sites and
      74% of the control teeth. At teeth treated with the combined surgical procedure,
      the mean gain in probing attachment amounted to 3.7 mm and the mean gingival
      height had increased to 3.5 mm (0.6). The corresponding figures for control teeth
      were 3.6 mm and 1.5 mm (0.5), respectively. At the 24-month follow-up
      examination, the mean root coverage amounted to 98.9% (test) and 97.1% (control).
      88% of the teeth in the test group showed complete root coverage compared to 80%
      for teeth in the control group. It was concluded that the 2 surgical procedures
      resulted in similar degree of root coverage and that changes of tooth brushing
      habits may be of greater importance than increased gingival thickness for long
      term maintenance of the surgically established position of the soft tissue
      margin.

PMID- 8877665
TI  - Mouthrinses containing triclosan reduce the incidence of recurrent aphthous
      ulcers (RAU).
AB  - Triclosan, an antibacterial agent introduced in toothpastes and mouthrinses, has
      recently been shown to have anti-inflammatory and analgesic properties. The aim
      of the present double-blind cross-over study was to examine the effect of
      triclosan on the incidence of recurrent aphthous ulceration (RAU) when
      administered in mouthrinses. The study included 30 patients with a history of
      multiple recurrent aphthous ulcers. Three different triclosan-containing
      mouthrinses, differing only in their solubilizing agents were used and compared
      with a control rinse. The number of new ulcers, ulcer-free days and the severity
      of pain were recorded. The results showed that the patients experienced a
      significant decrease in the number of oral ulcers during the experimental period
      when the mouthrinses contained triclosan. It may thus be concluded that triclosan
      has the potential to reduce the number of aphthous ulcers presumably due to its
      anti-inflammatory properties.

PMID- 8877666
TI  - 2 multi-center trials assessing the clinical efficacy of 5% sanguinarine in a
      biodegradable drug delivery system.
AB  - A biodegradable drug delivery system containing 5% sanguinarium (Sa) was compared
      to vehicle control (VC), scaling and root planing (SRP), and supragingival plaque
      control (SPC) in the treatment of adult periodontitis in 2 well-controlled
      clinical trials. Studies were 4-quadrant (split mouth) designs at 2 centers each,
      having 94 (Study A) and 107 (Study B) patients. All patients had at least 3
      pockets between 5 and 9 mm that bled on probing, in each quadrant. Probing pocket
      depth (PD), clinical attachment level (AL), bleeding on probing (BOP), and plaque
      index were recorded at baseline, 14, 30, 60, and 90 days. All treatments gave
      statistically significant reductions from baseline for PD and BOP, and
      significant gains for AL. For PD reduction, SRP was superior to all test groups
      at all time points in both studies (p < 0.001). Sa was superior to VC in Study A
      at 14 and 30 days and to SPC at all time points. For AL gain at 90 days, in both
      studies, SRP gave gains of 0.42 and 0.78 mm respectively with superiority seen
      over the SPC group at 90 days (p < 0.001) in study A only, For BOP reduction, in
      Study A SRP was superior to Sa, VC, and SPC at 60 and 90 days (p < 0.005) and in
      Study B superiority to Sa and VC was at 90 days and to SPC at 60 days (p < 0.05).
      Sa was superior to VC for pocket depth in deep pockets only. Sa failed to
      demonstrate superiority over VC on a consistent basis. Analysis of residual Sa
      indicates that Sa potency was insufficient to show an advantage beyond clinical
      effects inherent in treatments with VC and SPC.

PMID- 8877667
TI  - Psychosocial factors and adult onset rapidly progressive periodontitis.
AB  - On the basis of clinical observations, some periodontologists have suggested an
      association between psychosocial factors such as depression, stress and anxiety,
      and adult onset rapidly progressive periodontitis (RPP). This study investigated
      more formally possible associations between a number of relevant psychosocial
      factors and RPP. The significance of the psychosocial variables was assessed by
      comparing 3 groups: 50 patients with RPP, 50 patients with routine chronic adult
      periodontitis (RCAP), and 50 patients without significant periodontal destruction
      (controls). It was anticipated that the RPP group would show higher levels of
      psychosocial maladjustment than the RCAP and control groups. A between-subjects
      multivariate analysis of covariance indicated that the combined psychosocial
      variables were significantly related to the periodontal diagnosis. 2 psychosocial
      factors, depression and loneliness, were significant in distinguishing between
      groups. The RPP group presented significantly increased depression and loneliness
      compared to the RCAP and control groups. Future research is indicated to further
      clarify the significance of these psychosocial differences in relation to the
      onset and progression of RPP.

PMID- 8877669
TI  - A classification of drug action based on therapeutic effects.
AB  - A systematic classification system has been developed for the categorization of
      therapeutic effects of individual drugs based on their relationships to the
      underlying disease processes being treated or prevented, rather than on the
      pharmacologic or biochemical effects of the individual drugs. This system
      involves a total of six categories of different therapeutic specificities,
      involving four categories based on disease process-oriented mechanisms of drug
      action (Categories I through IV), and two additional ones (Categories 0 and V) to
      complete the classification system. Category 0 includes drugs or drug uses that
      prevent the development of a disease when none exists; Category I, those that
      affect etiologic factors of a disease; Category II, those that affect specific
      disease processes; Category III, those that affect specific disease
      manifestations; Category IV, those that affect non-specific disease
      manifestations or symptoms; and Category V includes drug uses or drugs used to
      diagnose or facilitate treatment of a disease. Examples are provided for each
      category as well as for applications of the classification system.

PMID- 8877668
TI  - Some effects of mouthrinses containing salifluor on de novo plaque formation and
      developing gingivitis.
AB  - Three clinical trials were carried out to evaluate the effects of mouthrinses
      containing 5n-octanoyl-3'-trifluormethylsalicylanilide (salifluor) on plaque and
      gingivitis. Each trial was performed as a double-blind, randomised and cross-over
      designed study (studies 1, 2 and 3). In each study, 10 young individuals with
      healthy gingiva abolished all means of mechanical plaque control during the
      course of the experimental period including 6 x 4 days (study 1), 3 x 18 days
      (study 2) and 3 x 14 days (study 3). They rinsed, 2 x daily, with various
      mouthwash preparations for 4 days (study 1), for the last 4 days of a 18 day
      period (study 2) or for 14 days (study 3). 6 (control, vehicle control, 0.08%,
      0.12% and 0.2% salifluor and 0.12% chlorhexidine), 3 (control, 0.12% salifluor
      and 0.12% chlorhexidine) and 3 (control, 0.12% salifluor and 0.12% chlorhexidine)
      mouthwash preparations were tested in studies 1, 2 and 3, respectively. The
      findings of study 1 indicated that (i) mouthrinses containing salifluor were
      significantly more effective than control rinses and that (ii) the salifluor
      mouthrinses were equally effective as the 0.12% chlorhexidine mouthrinse, in
      retarding 4-day de novo plaque formation. The findings of study 2 indicated that
      (i) the mouthrinse containing 0.12% salifluor retarded de novo plaque formation
      to the same extent as the 0.12% chlorhexidine mouthrinse at healthy as well as at
      inflamed sites but that (ii) the anti-plaque effects of the salifluor and
      chlorhexidine mouthrinses were significantly smaller at sites with inflamed than
      with healthy gingiva. In study 3, it was observed that there was no significant
      difference between the 0.12% salifluor and 0.12% chlorhexidine mouthrinses in
      retarding de novo plaque formation and the development of gingivitis during a 14
      day period of no mechanical plaque control. Thus, the results of the 3 clinical
      trials demonstrated the potential of salifluor as an effective anti-plaque and
      anti-inflammatory agent.

PMID- 8877670
TI  - Failure to comply: a therapeutic dilemma and the bane of clinical trials.

PMID- 8877671
TI  - Clinical geriatric psychopharmacology: drugs and neuropsychiatric symptoms. A
      clinical pharmacology problem solving unit.

PMID- 8877672
TI  - Effect of a combination of gemfibrozil and niacin on lipid levels.
AB  - To determine the effect of the combination of niacin and gemfibrozil on the lipid
      profile, a retrospective review was conducted of 161 patients who were prescribed
      a combination of gemfibrozil and niacin for 6 to 12 months at a community-based
      lipid clinic. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
      cholesterol, total cholesterol, triglycerides, ratio of total cholesterol to HDL,
      alanine aminotransferase (ALT), and weight were measured at entry to the clinic,
      2 months after dietary instruction, during single-agent therapy, and during
      combination therapy. Mean doses of niacin and gemfibrozil were 1,229 mg/day and
      1,200 mg/day, respectively. Patient weight decreased significantly after dietary
      instruction and after institution of combination therapy. There were no
      significant changes in ALT levels with either single-agent therapy or with
      combination therapy. The combination of niacin and gemfibrozil produced marked
      and significant changes in lipid levels: total cholesterol and LDL decreased by
      14%, HDL increased by 24%, the ratio of total cholesterol to HDL decreased by
      30%, and triglycerides decreased by 52%. The combination of niacin and
      gemfibrozil in the setting of dietary instruction has a marked beneficial effect
      on serum lipid levels, and was most effective in patients with initial levels of
      HDL < 40 mg/dL, triglycerides > 250 mg/dL, and LDL > 160 mg/dL. No episodes of
      ALT elevation or symptomatic myositis were seen.

PMID- 8877673
TI  - A comparison of the antihypertensive effectiveness of a combination of moexipril
      or sustained-release verapamil with low-dose hydrochlorothiazide.
AB  - The antihypertensive effectiveness of moexipril, a new angiotensin-converting
      enzyme (ACE) inhibitor, and sustained-release verapamil (verapamil SR) in
      combination with low-dose hydrochlorothiazide was investigated in patients with
      moderate to severe (Stages II and III) essential hypertension. Of 147 patients
      treated for 4 weeks with hydrochlorothiazide 25 mg/day, 108 patients with sitting
      diastolic blood pressure (SDBP) of 100 to 114 mmHg were randomly assigned to
      receive either moexipril 7.5 mg/day (n = 56) or verapamil SR 180 mg/day (n = 52)
      in addition to hydrochlorothiazide 25 mg/day. After 4 weeks of treatment, doses
      of moexipril or verapamil SR were increased to 15 and 240 mg/ day respectively
      for patients with SDBP of > or = 90 mmHg. These patients were evaluated for an
      additional 8 weeks. Electrocardiograms, blood chemistries, blood counts,
      urinalysis, plasma renin activity, and plasma aldosterone levels were monitored
      during the study. Moexipril or verapamil SR, in combination with low dose
      hydrochlorothiazide, resulted in decreased blood pressure in the sitting and
      standing positions. No correlation between blood pressure response and baseline
      plasma renin activity was demonstrated. The results of this study indicate that
      both moexipril and verapamil SR produced an additive hypertensive effect when
      added to low-dose hydrochlorothiazide. These combinations were well tolerated by
      the patients and did not result in serious clinical and metabolic side effects.

PMID- 8877674
TI  - Lymphocyte responsiveness to glucocorticoids, cyclosporine, or both.
AB  - The reason why some patients with glomerular diseases respond to steroid
      treatment and others do not remains obscure, and it is not possible to
      prospectively evaluate the probability of response in individual patients. One
      factor that might contribute to the clinical response to treatment could be the
      relative sensitivity of a patient's immune system to the suppressive effects of
      steroids or other immunosuppressive agents. To evaluate this possibility,
      phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC)
      from 16 patients with various biopsy-proven glomerulopathies were cultured with
      prednisolone or methylprednisolone in final concentrations of 10(-5) to 10(-8)
      mol/L. From the dose-response curves, the concentration of steroid required to
      cause 50% inhibition (IC50) of the PHA-induced proliferative response was
      determined. The PBMC from 10 patients also were cultured with 400 ng/mL
      cyclosporine both alone and with 10(-7) mol/L steroid, and the inhibitory effects
      were calculated. There was considerable heterogeneity in the sensitivities of
      individual patients to steroid inhibition, and the mean +/- SEM IC50 was
      significantly lower for methylprednisolone than for prednisolone. Cyclosporine
      caused 50% or greater inhibition in 6 of the 10 patients but had < 10% inhibitory
      effect in 2 patients. In most patients studied, cyclosporine plus steroid was
      significantly more inhibitory than cyclosporine alone, but the combination was
      usually no more effective than 10(-7) mol/L methylprednisolone alone. These
      results are consistent with the hypothesis that differences in the sensitivity of
      individual patient's immune systems to the immunosuppressive effects of steroids
      and cyclosporine might contribute to differences in their clinical responsiveness
      to treatment.

PMID- 8877675
TI  - Population pharmacokinetics of intravenous amiodarone in patients with refractory
      ventricular tachycardia/fibrillation.
AB  - A population approach was used to determine the pharmacokinetics of amiodarone in
      245 patients receiving intravenous amiodarone for the short-term treatment of
      refractory, hemodynamically destabilizing, ventricular tachycardia and/or
      fibrillation. A two-compartment model employing proportional statistical models
      to estimate intersubject variability and an additive-proportional model to
      estimate residual error were found to best describe the data. The mean (%
      coefficient of variation, CV) value for clearance was 0.22 L/hr/kg (13%), central
      volume of distribution was 0.30 L/kg (11%), peripheral volume of distribution was
      10.0 L/kg (9.5%), and intercompartmental clearance was 0.71 L/hr/kg (16%). The
      mean (%CV) intersubject variance estimates were 1.52 (31%) for clearance, 0.37
      (46%) for central volume, 0.37 (67%) for peripheral volume, and 0.44 (39%) for
      intercompartmental clearance. The estimate of residual error (%CV) was 0.53
      (13%). Age, gender, height, serum creatinine concentration, serum alkaline
      phosphatase activity, ejection fraction, and therapeutic response to treatment
      did not contribute to the variability in patient pharmacokinetics. It was
      concluded that the pharmacokinetic parameters of amiodarone in these patients
      were similar to those reported for healthy volunteers and were similarly
      variable. Estimates of pharmacokinetic parameters made during short periods of
      observation may not be entirely consistent with parameters estimated during
      prolonged periods of observation of healthy volunteers who receive single doses.

PMID- 8877676
TI  - Pharmacokinetics of intravenous amiodarone in patients with impaired left
      ventricular function.
AB  - To evaluate the potential need for modification of dose regimens of intravenous
      amiodarone in patients with left ventricular dysfunction, the pharmacokinetics of
      amiodarone and its active metabolite, desethylamiodarone (DEA), were examined
      after a single 15-minute intravenous infusion of amiodarone 5 mg/kg. Three
      parallel groups of otherwise healthy volunteers with normal (n = 12), moderately
      impaired (ejection fraction > 30 but < or = 45%; n = 6), or severely impaired
      (ejection fraction < or = 30%; n = 6) left ventricular function were enrolled in
      the study. Serial blood samples were obtained over a 76-day period for estimation
      of pharmacokinetic parameters. With the exception of the half-life (t1/2) of DEA,
      statistical comparisons revealed no significant between-group differences in
      pharmacokinetic parameters or correlations between pharmacokinetic parameters and
      ejection fractions. The t1/2 of DEA was increased by approximately 60% in
      patients with severe left ventricular dysfunction compared with that in patients
      with moderately impaired and normal left ventricular function. The rate of DEA
      formation is slow, however, and its concentration relative to amiodarone is low.
      Therefore, it is unlikely that concentrations of DEA in serum would reach levels
      that contribute significantly to the pharmacologic activity of amiodarone during
      short-term (up to 2 weeks) intravenous amiodarone therapy. Single doses of
      amiodarone were well tolerated. The results of this study suggest that
      intravenous amiodarone can be used with appropriate observation to control
      arrhythmias, regardless of the degree of left ventricular dysfunction.

PMID- 8877677
TI  - Tolerance and pharmacokinetics of single-dose atorvastatin, a potent inhibitor of
      HMG-CoA reductase, in healthy subjects.
AB  - Tolerance and pharmacokinetics after single-dose administration of atorvastatin,
      an investigational inhibitor of HMG-CoA reductase, were examined in 22 healthy
      volunteers in a three-period, partially-blinded study. Participants received
      capsule and solution doses of atorvastatin (0.5 to 120 mg) and placebo at weekly
      intervals. Atorvastatin was well tolerated at doses as high as 80 mg. The adverse
      event profile was similar after administration of atorvastatin capsules and
      placebo. Atorvastatin solution was slightly less well tolerated. The most common
      side effect after administration of capsules and solution was headache, followed
      by sporadic reports of diarrhea, flatulence, and nausea. At the 120-mg solution
      dose, one participant experienced mild, transient restlessness, euphoria, and
      mental confusion that were considered to be dose-limiting side effects. Mean
      concentrations of atorvastatin, maximum concentration (Cmax), and area under the
      concentration-time curve from time 0 to the time of the last detectable
      concentration (AUCo-tldc) increased with increasing dose. Plasma elimination half
      life (t1/2) ranged from 14.7 to 57.6 hours. The bioavailability of atorvastatin
      capsules was similar to that of solution. These results suggest that atorvastatin
      is well tolerated after single doses as high as 80 mg, and may require
      administration only once daily.

PMID- 8877678
TI  - Pharmacokinetics of testosterone in hypogonadal men after transdermal delivery:
      influence of dose.
AB  - To assess the pharmacokinetics of testosterone after application of one, two, or
      three testosterone transdermal delivery systems to hypogonadal patients, 12
      hypogonadal men (mean age 46.6 +/- 10.5 years) were enrolled in an open-label,
      randomized, crossover study. Each application period comprised 4 days: a 2-day
      washout period with no exogenous testosterone therapy followed by 2 days of
      therapy with one, two, or three transdermal systems applied daily to the
      patient's back. On day 4 of each period, serial blood samples were collected for
      determination of total and non-sex hormone binding globulin (non-SHBG) bound
      serum testosterone concentrations. Serum concentrations of testosterone were
      determined using validated radioimmunoassay methods. Residual testosterone
      analysis of used transdermal systems was used to estimate testosterone delivery
      through the skin. In general, serum concentrations of testosterone rose in
      accordance with an increase in dose. Using a strict bioequivalence approach to
      dose proportionality, the increases in area under the concentration-time curve
      (AUC) and morning concentrations were proportional to the increase in dose from
      two to three transdermal systems, but somewhat less than proportional with an
      increase from one to two transdermal systems. Results from the non-SHBG bound
      serum testosterone concentrations closely paralleled those of total serum
      testosterone. Use of three transdermal systems yielded serum concentrations of
      testosterone that tended to be above the upper limit of the normal range. The AUC
      and cumulative release of testosterone were linearly related to the number of
      applied systems. If necessary, the standard recommended dose of two testosterone
      transdermal delivery systems can be modified to accommodate interindividual
      differences in testosterone requirements of hypogonadal men.

PMID- 8877679
TI  - Predominance of slow acetylators of N-acetyltransferase in a Hmong population
      residing in the United States.
AB  - Pharmacogenetics can be an important determinant of pharmacologic response. To
      learn more about interpopulation differences in drug metabolism between
      ethnically diverse populations of subjects cared for by an International Clinic,
      a study was conducted to describe the prevalence of fast or slow acetylators of N
      acetyltransferase (NAT2) in a population of Hmong residing in Minnesota. Ninety
      eight healthy Hmong refugees from Laos volunteered to take caffeine as an oral
      probe drug to establish acetylator phenotype. Participants were classified as
      either rapid or slow acetylators based on the urinary molar ratio of select
      metabolites of caffeine. Assignment of phenotype was based on results from
      analysis of urine collected subsequent to ingestion of caffeine. The ratio of 5
      acetylamino-6-formylamino-3-methyluracil (AFMU) to the combined products of the 7
      demethylation pathway of paraxanthine (AFMU, 1-methylxanthine (1X), and 1
      methylurate (1U)] formed the basis for this determination. A probit plot of the
      data collected in our subjects qualified a metabolic ratio of 0.34 as an
      acceptable cut point for phenotype assignment. Participants with an AFMU/(AFMU +
      1X + 1U) ratio of < 0.34 were classified as slow acetylators and all others as
      rapid acetylators. Analysis of the data suggested a bimodal distribution with an
      excess (74.5%) of slow acetylators in the population. The predominance of slow
      acetylators found in the Hmong contrast with the prevalence of slow acetylators
      seen in other ethnic groups. These findings may have important clinical
      implications given the large number of Hmong treated each year in our
      International Clinic and the increasing use of medications metabolized by NAT2 in
      this population.

PMID- 8877680
TI  - Evaluation of sex differences in the pharmacokinetics of ranitidine in humans.
AB  - A bioequivalence study of two oral formulations of 300 mg ranitidine was carried
      out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in
      both sexes were compared. There was bioequivalence of both formulations. The
      terminal half-life of ranitidine was 7% shorter and the oral apparent clearance
      10.5% higher in women (1.44 L/h/kg) than in men (1.29 L/h/kg), although this
      difference did not reach statistical significance. No differences were observed
      in maximum concentration (Cmax) or the time of its occurrence (tmax). Sex, age,
      and weight did not correlate significantly with oral clearance. These results
      suggest that there are no sex differences in the pharmacokinetics of ranitidine,
      or that any differences would not be of clinical relevance. It also should be
      emphasized that bioequivalence trials also can be used to study other
      pharmacokinetic or pharmacodynamic characteristics of drugs without damaging the
      main endpoint of the study.

PMID- 8877681
TI  - Detection of carbamazepine drug interaction by multiple peak approach screening
      using routine clinical pharmacokinetic data.
AB  - Multiple peak approach screening was used to detect the effects of other
      antiepileptic drugs on the population estimates of relative clearance of
      carbamazepine. Routine clinical pharmacokinetic data (N = 1,010) collected from
      466 patients receiving carbamazepine were analyzed according to a simple steady
      state pharmacokinetic model with the use of NONMEM, a computer program designed
      for population pharmacokinetic analysis that allows pooling of data. NONMEM
      estimates indicated that carbamazepine clearance decreased nonlinearly with
      increasing total body weight (TBW) in the maturation process (over an age range
      of 5 months to 15 years) and increased nonlinearly with increasing daily dose
      (mg/kg) of carbamazepine. Concomitant administration of other antiepileptic drugs
      resulted in an increased in clearance of carbamazepine as follows: valproic acid
      alone (VPA), 7%; phenobarbital alone (PB), 16%; more than two antiepileptic drugs
      (POLY), 27%. Final regression model of relative clearance (Cl) for all data was:
      Cl (mL/hr/kg) = 64.9. TBW (kg)-0.336.DOSE (mg/kg/day)0.465 1.07VPA 1.16PB
      1.27POLY.

PMID- 8877682
TI  - Acebutolol overdose treated with hemodialysis and extracorporeal membrane
      oxygenation.
AB  - A case involving a 27-year-old woman who ingested an overdose of acebutolol is
      presented. Extracorporeal membrane oxygenation was initiated to stabilize the
      patient's condition before commencing hemodialysis. S-diacetolol (the N
      acetelation product of acebutolol) was cleared with hemodialysis. It is suggested
      that extracorporeal membrane oxygenation may be of short-term benefit in the
      treatment of overdoses with beta-adrenergic agents such as acebutolol when
      accelerated clearance with hemodialysis is anticipated.

PMID- 8877683
TI  - Ethnic comparability of the MMPI in pain patients.
AB  - The MMPI basic validity and clinical scales' patterns of 295 White-, African- and
      Latino-American pain patients were compared. Mean group differences across ethnic
      groups on scales L, F, K, Mf, and Si were revealed in multivariate analysis of
      covariance for females, while differences across ethnic groups on scales F, K,
      Mf, Sc, Ma, and Si were revealed for males. In the univariate follow-up analyses
      of covariance, significant main effects were obtained for ethnicity along with
      education and (occasionally for males) duration of pain. Various high-point, two
      point, and other profile patterns were examined and notable gender/ethnic group
      differences were found. The pattern of intercorrelations of the MMPI scales mean
      T scores with various demographic and clinical characteristics suggested some
      notable divergence across subgroups on certain correlates of the pain experience.

PMID- 8877684
TI  - The role of dysphoric mood and gender in interpersonal responses to nondysphoric
      others.
AB  - There now exists a sizeable body of research on interpersonal responses to
      dysphoric individuals, yet relatively few studies have addressed responses of
      dysphoric individuals toward others. This study compared responses of dysphoric
      and nondysphoric individuals toward a nondysphoric person within same sex and
      opposite-sex dyads. Dysphoric and nondysphoric subjects did not differ in their
      desire for future interaction with their interactional partner. Dysphoric
      subjects reported a greater reduction in feelings of sadness, hostility, and
      impatience following the interaction, and among dysphoric subjects, those who
      interacted with a female reported a greater decrease in anxiety than did those
      who interacted with a male. Dysphoric subjects also perceived their partners to
      act in a more dysphoric fashion than did nondysphoric subjects.

PMID- 8877685
TI  - Severe weather phobia: an exploratory study.
AB  - Eighty-one persons with an intense fear of severe thunderstorms and tornadoes
      were interviewed to learn more about the phenomenon of "severe weather phobia," a
      term introduced for the first time in this investigation. Possible causes and
      methods of treatment are discussed, as well as implications for future research.

PMID- 8877686
TI  - Comparing two self-report measures of coping--the Sense of Coherence Scale and
      the Defense Style Questionnaire.
AB  - Antonovsky's Sense of Coherence Scale (SOC) and Bond's Defense Style
      Questionnaire (DSQ) were compared in a sample of 334 community controls and 122
      psychiatric outpatients. The major question was, whether the two coping
      inventories with different theoretical backgrounds-stress research vs. psycho
      analysis-tap similar phenomena. The affinity of the two coping measures was
      evident: in multiple regression analysis defenses explained 68% of the variance
      in sense of coherence. Not surprisingly, the SOC scale-emerging out of the
      salutogenic orientation-showed more expertise in measuring how people manage when
      they do well, whereas the DSQ-with its theoretical roots deep in psychopathology
      was most sensitive to how people manage when they do rather poorly.

PMID- 8877687
TI  - Faking the MMPI-2: utility of the Subtle-Obvious scales.
AB  - We explored the effect of different subject response sets on the profile
      configuration of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and
      the utility of traditional validity, Back F, and Subtle-Obvious scales in
      detecting response set. College students were administered the MMPI-2 under one
      of three response sets; faking good, faking bad, or standard report. Results
      revealed significant differences across the three response set groups on all
      clinical, content, validity, obvious, and two of the five subtle scales in the
      expected direction. Additionally, respondents in the faking conditions produced
      consistent T-score patterns and significant O-S differences on the Subtle-Obvious
      scales. Examination of these subtle-obvious patterns may offer clinicians
      valuable information regarding profile validity beyond that offered by the
      traditional validity and Back F scales.

PMID- 8877688
TI  - Performance of female college students and sexual abuse survivors on the Brief
      Symptom Inventory.
AB  - The relation between childhood molestation and current adjustment, as measured by
      the Brief Symptom Inventory (BSI), was examined among women college students.
      Results suggest that the normative data available for the BSI are inappropriate
      for interpreting the performance of women college students and, particularly,
      students who have survived sexual abuse.

PMID- 8877689
TI  - The Hopelessness Scale for Children: psychometric properties with hospitalized
      adolescents.
AB  - This study examined the internal consistency and factor structure of the
      Hopelessness Scale for Children with 201 adolescent inpatients (M age = 15.4
      years). In comparison to the psychometric properties of the scale found with
      younger children, our findings suggest adequate, but lower, internal consistency
      reliability and a weak core factor structure. The results are discussed in terms
      of possible changes in the child scale or the alternative use of an adult measure
      of hopelessness with adolescents.

PMID- 8877690
TI  - Cross-cultural validation of Antonovsky's Sense Of Coherence Scale.
AB  - This study empirically validated Antonovsky's suggestion that a Sense of
      Coherence is important in managing stress and remaining both physically and
      psychologically healthy. In both Anglo-American and Native American cultures,
      Sense of Coherence Measures were found to correlate negatively with measures of
      physical and mental distress. More interestingly, this study supported
      Antonovsky's prediction that people from various cultures may attain a similar
      level of a Sense of Coherence, despite great socioeconomic differences.

PMID- 8877691
TI  - Convergent validity of the Depression-Happiness Scale with measures of
      depression.
AB  - In recent years, the study of subjective well-being (SWB) has attracted much
      research interest. One recent operational definition of SWB is the McGreal and
      Joseph (1993) Depression-Happiness Scale. The aim of the present research was to
      investigate the convergent validity of the Depression-Happiness Scale with
      several other well established measures of depressive symptomatology. Subjects
      were 194 undergraduate students attending the University of Ulster. Lower scores
      on the Depression-Happiness Scale, indicating a higher frequency of negative
      thoughts and feelings and a lower frequency of positive thoughts and feelings,
      were associated with higher scores on the Beck Depression Inventory, the Self
      Rating Depression Scale, and the Center for Epidemiological Studies Depression
      Scale. These data provide further evidence for the convergent validity of the
      Depression-Happiness Scale.

PMID- 8877692
TI  - Factor structure of the Beck Hopelessness Scale.
AB  - The factor structure of the Beck Hopelessness Scale (BHS; Beck & Steer, 1988) was
      examined among 411 outpatients (male = 132, female = 272, unknown = 7). Varimax
      rotated principal-components analysis extracted three factors greater than unity
      that accounted for 40.4%, 6.9%, and 5.6% of the variance. Because the structure
      was invariant across factor rotations and levels of hopelessness severity, it is
      concluded that the BHS consists of three factors (Expectations of Success,
      Expectations of Failure, and Future Uncertainty).

PMID- 8877693
TI  - Is health locus of control a 3-factor or a 2-factor construct?
AB  - Although the Multidimensional Health Locus of Control (MHLC) scales are commonly
      used, uncertainty about their factorial validity still remains. In the present
      study, confirmatory factor analyses of a French-Canadian adaptation of the
      Multidimensional Health Locus of Control scales (MHLC) were conducted to compare
      in a non-clinical group of 224 adults two factor models. Multigroup analyses were
      also conducted using this group and a clinical group of 132 diabetics to assess
      the equivalence of the MHLC factor structure across these two groups. A 3-factor
      model postulating an internal, external, and chance dimension, and accounting for
      measurement errors provided the best fit to the data. Multigroup analyses failed
      to support the equivalence of the MHLC factor loadings across the non-clinical
      and clinical group. These findings suggest that comparisons of MHLC scores across
      such groups may be problematic.

PMID- 8877694
TI  - MMPI-2 interpretation and stroke: cross-validation of a correction factor.
AB  - Accumulating data indicate that the MMPI-2 contains items that may be sensitive
      to neurologic conditions independent of a patient's psychological status. Gass
      (1992) identified 21 stroke-related MMPI/MMPI-2 items which were recommended for
      use as a score-correction index. This study examined these items using a cross
      validation sample of 50 VA stroke patients. Item endorsement rates were
      contrasted with those of the MMPI-2 normative sample. The following results were
      obtained: The MMPI-2 items that distinguished stroke patients from normals have
      neurologic symptom content, all 21 correction items were upheld as effective
      discriminators, and the 21 items were commonly endorsed by the CVA patients (mean
      = 52%, range: 22% to 75%). These findings support the composition of the MMPI-2
      correction for stroke and the rationale on which its application is based.

PMID- 8877695
TI  - MMPI-2 profiles in traumatic and non-traumatic spinal cord injured patients.
AB  - This study investigated the relationship of type of onset of disability to the
      MMPI-2 profiles of 73 spinal cord patients receiving comprehensive inpatient
      rehabilitation. Participants were divided into three onset groups: non-traumatic,
      passive-traumatic, and active-traumatic (active and passive participation in the
      injury). A 2 x 3 factorial MANOVA (gender and onset) with age as a covariate was
      performed on the MMPI-2 profiles. A main effect for gender (scales D and MAC-R)
      was found. The medical and functional impairments common to the onset subtypes
      suggest a somato-psychic direction in psychological adjustment.

PMID- 8877696
TI  - Measuring the effect of the Rorschach color cards (VIII-X) on perceptual accuracy
      and special scores in differentiating borderline from schizophrenic protocols.
AB  - In this study, measures were developed that compared conventional Form accuracy
      and the ratio of Special Scores on Cards VIII-X (Color Cards) with overall
      Rorschach scores. Two new measures, a Color Card Perception Difference (CCPD)
      score and a Special Score Difference (SSD) score were used for this purpose. CCPD
      and SSD scores were calculated by subtracting component X + % scores and weighted
      Special Score ratios found on the overall Rorschach from those unique to Cards
      VIII-X. CCPD scores were found to be highly effective in differentiating a
      previously diagnosed borderline from a schizophrenic group. CCPD and SSD scores
      were correlated with MMPI scales for profile characteristics.

PMID- 8877697
TI  - Correspondence of MMPI and MMPI-2 with chemically dependent patients.
AB  - One hundred (39 women and 61 men) hospitalized substance abusers were
      administered the MMPI and MMPI-2. The correspondence of T-Scores, Codetypes, and
      MAC/MAC-R scores were analyzed. Results showed that the MMPI-2 produced profiles
      that were consistent with previous research on the MMPI with substance abusers.
      However, the relationship between MMPI and MMPI-2 T-scores appeared complex and
      varied across individual scales for both men and women. Codetype congruence was
      38% for one, two, and three-point code-types. Well-defined codetypes accounted
      for 30% of the profiles. MAC/ MAC-R raw scores were different for men but not for
      women. Codetypes established for the MMPI may not be fully transferable to the
      MMPI-2 in a substance abusing population.

PMID- 8877698
TI  - Towards the automatic design of synthetically accessible protein ligands:
      peptides, amides and peptidomimetics.
AB  - The computer program LUDI for the de novo design of protein ligands was extended
      so that it is now able to take into account the synthetic accessibility of the
      constructed molecules. As an example, the design of peptides, amides and
      peptidomimetics using amino acids as building blocks is described. Two new
      libraries containing natural and non-natural amino acids were constructed for
      this purpose. Conformational flexibility is taken into account by using multiple
      conformers for each amino acid. The program was applied to the design of ligands
      for the enzymes elastase, renin and thermolysin.

PMID- 8877699
TI  - Wavelets and molecular structure.
AB  - The wavelet method offers possibilities for display, editing, and topological
      comparison of proteins at a user-specified level of detail. Wavelets are a
      mathematical tool that first found application in signal processing. The
      multiresolution analysis of a signal via wavelets provides a hierarchical series
      of "best' lower-resolution approximations. B-spline ribbons model the protein
      fold, with one control point per residue. Wavelet analysis sets limits on the
      information required to define the winding of the backbone through space,
      suggesting a recognizable fold is generated from a number of points equal to 1/4
      or less the number of residues. Wavelets applied to surfaces and volumes show
      promise in structure-based drug design.

PMID- 8877700
TI  - A proposed common spatial pharmacophore and the corresponding active
      conformations of some peptide leukotriene receptor antagonists.
AB  - Molecular modeling studies were carried out by a combined use of conformational
      analysis and 3D-QSAR methods of identify molecular features common to a series of
      hydroxyacetophenone (HAP) and non-hydroxyacetophenone (non-HAP) peptide
      leukotriene (pLT) receptor antagonists. In attempts to develop a ligand-binding
      model for the pLT receptor, the Apex-3D program was used to identify biophoric
      structural patterns that are common to 13 diverse sets of compounds showing
      different levels of biological activity. A systematic conformational analysis was
      carried out to obtain sterically accessible conformations for these flexible
      compounds. Apex-3D was then utilized to propose common biophoric regions based on
      the selection of one of several conformations (MOPAC-minimized AM1) from each
      compound's data set that best fits the biophoric pattern and the resulting
      superimposition with all the other data-set compounds. Apex-3D identified three
      common biophoric features important for activity: one as the hydroxyl, acetyl,
      carbonyl and carboxyl groups, which mimic the acid-binding region of an agonist,
      the other as the hydrogen-bond donating site, and the third part is represented
      by a plane in which lipophilic aromatic groups align. The structure-activity
      relationships were then assessed by using the 3D-QSAR model. A common biophore
      model is proposed from the Apex-3D analysis which may be useful in designing new
      pLT antagonists. Molecular volumes and electrostatic potential similarities were
      also calculated in order to obtain the important structural requirements for the
      activity.

PMID- 8877702
TI  - Comparative docking studies on ligand binding to the multispecific antibodies IgE
      La2 and IgE-Lb4.
AB  - A large comparative study is presented in which the binding of approximately 30
      different ligands to two IgE antibodies (La2 and Lb4) is analyzed by means of an
      automated-docking procedure based on simulated annealing. The method is able to
      reproduce experimentally verified binding orientations, as shown by application
      to the Ig-AN02-hapten complex. The main address of the study is to investigate
      the concept of antibody multispecificity. Problems and usefulness of docking in
      this context are discussed. The results indicate reasons for multispecific
      binding properties and how they can be understood from the topology of the
      binding site. Though similar in general behaviour, the two antibodies show
      interesting differences in their binding characteristics. The binding sites of
      both antibodies are described and the main interacting residues revealed.

PMID- 8877701
TI  - Distributed automated docking of flexible ligands to proteins: parallel
      applications of AutoDock 2.4.
AB  - AutoDock 2.4 predicts the bound conformations of a small, flexible ligand to a
      nonflexible macromolecular target of known structure. The technique combines
      simulated annealing for conformation searching with a rapid grid-based method of
      energy evaluation based on the AMBER force field. AutoDock has been optimized in
      performance without sacrificing accuracy; it incorporates many enhancements and
      additions, including an intuitive interface. We have developed a set of tools for
      launching and analyzing many independent docking jobs in parallel on a
      heterogeneous network of UNIX-based workstations. This paper describes the
      current release, and the results of a suite of diverse test systems. We also
      present the results of a systematic investigation into the effects of varying
      simulated-annealing parameters on molecular docking. We show that even for
      ligands with a large number of degrees of freedom, root-mean-square deviations of
      less than 1 A from the crystallographic conformation are obtained for the lowest
      energy dockings, although fewer dockings find the crystallographic conformation
      when there are more degrees of freedom.

PMID- 8877703
TI  - Towards an understanding of the molecular basis of hydrophobicity.
AB  - The modern view is stressed that the structuring of water around nonpolar
      solutes, a process called hydrophobic hydration, actually favors the solubility
      of nonpolar solutes in water, its associated positive free energy of transfer
      arising from the enthalpic input required to create a cavity in water to
      accommodate the solute. The results of a series of molecular dynamics simulations
      of methane in SPC/E water at different temperatures are reported. These results
      show the existence of a larger fraction of broken hydrogen bonds in the hydration
      shell water of the nonpolar solutes with respect to the bulk water, the
      difference increasing with a rise in temperature. This supports Muller's modified
      hydration-shell hydrogen-bond model predictions, where hydration-shell water
      molecules have lower free energies of hydrogen-bond breaking than those in the
      bulk.

PMID- 8877704
TI  - Comparison of cyclic delta-opioid peptides with non-peptide delta-agonist
      spiroindanyloxymorphone (SIOM) using the message-address concept: a molecular
      modeling study.
AB  - Based upon the message-address concept, this molecular modeling study used the
      delta-selective agonist spiroindanyloxymorphone (SIOM) as a molecular template
      for a conformational search and analysis of delta-selective opioid peptides. It
      was assumed that the tyramine moiety plays the same role for delta-opioid
      receptor recognition in both peptide and non-peptide ligands. Using 20 reported
      low-energy conformations of Tyr-cyclo[D-Cys-D-Pen]-OH (JOM-13) for comparison,
      the geometrical relationship of the two aromatic rings present in SIOM was used
      for the identification of potential active conformations of JOM-13, from which
      two delta-receptor-binding models (I and II) were constructed. Models I and II
      differ from each other in the arrangement of the peptide backbones. To evaluate
      the two models, a conformational search of two other known delta-selective
      ligands, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Pen2,L-Pen5]enkephalin (DPLPE)
      was performed, using the geometrical relationship of the two aromatic rings
      defined in the two receptor-binding models as a molecular template. Among the
      conformations generated from the molecular simulation, low-energy conformers of
      DPDPE and DPLPE conforming to models I and II were identified. Unlike model I,
      conformers of DPDPE and DPLPE that fit model II contain a cis amide bond in the
      Gly3 residue.

PMID- 8877706
TI  - PBSC collection following 67Ga infusion for a nuclear medicine study.

PMID- 8877705
TI  - Evolutionary algorithms in computer-aided molecular design.
AB  - In recent years, search and optimisation algorithms inspired by evolutionary
      processes have been applied with marked success to a wide variety of problems in
      diverse fields of study. In this review, we survey the growing application of
      these 'evolutionary algorithms' in one such area: computer-aided molecular
      design. In the course of the review, we seek to summarise the work to date and to
      indicate where evolutionary algorithms have met with success and where they have
      not fared so well. In addition to this, we also attempt to discern some future
      trends in both the basic research concerning these algorithms and their
      application to the elucidation, design and modelling of chemical and biochemical
      structures.

PMID- 8877707
TI  - Improved retroviral vectors for hematopoietic stem cell protection and in vivo
      selection.
AB  - Therapeutic gene transfer into hematopoietic cells is critically dependent on the
      evolution of methods that allow ex vivo expansion, high-frequency transduction,
      and selection of gene-modified long-term repopulating cells. Progress in this
      area needs elaboration of defined culture and transduction conditions for long
      term repopulating cells and improvement of gene transfer systems. We have
      optimized retroviral vector constructions based on murine leukemia viruses (MuLV)
      to overcome the transcriptional repression encountered with the use of
      conventional Moloney MuLV (MoMuLV) vectors in early hematopoietic progenitor
      cells (HPC). Novel retroviral vectors, termed FMEV (for Friend-MCF/MESV hybrid
      vectors), were cloned that mediate greatly improved gene expression in the
      myeloerythroid compartment. Transfer of the selectable marker multidrug
      resistance 1 (mdr1), FMEV, in contrast to conventional MoMuLV-related vectors
      currently in use for clinical protocols, mediated background-free selectability
      of transduced human HPC in the presence of myeloablative doses of the cytostatic
      agent paclitaxel in vitro. Furthermore, FMEV also greatly improved chemo
      protection of hematopoietic progenitor cells in a murine model system in vivo.
      Finally, when a second gene was transferred along with mdr1 in an FMEV-backbone,
      close to 100% coexpression was observed in multidrug-resistant colonies. These
      observations have significant consequences for a number of ongoing and planned
      gene therapy trials, for example, stem cell protection to reduce the myelotoxic
      side effects of anticancer chemotherapy, correction of inherited disorders
      involving hematopoietic cells, and antagonism of HIV infection.

PMID- 8877708
TI  - Allogeneic peripheral blood progenitor cells: current status and future
      directions.
AB  - Increasing use is being made of mobilized peripheral blood as a source of
      hematopoietic stem and progenitor cells for transplantation. Initially, these
      efforts were focused on autologous applications. However, many centers are now
      using cells derived from normal donors mobilized with recombinant hematopoietic
      growth factors for allogeneic transplantation. This article reviews the key
      issues associated with the use of these cells for hematologic reconstitution and
      summarizes important recent developments in the field.

PMID- 8877709
TI  - Concomitant mobilization of plasma cells and hematopoietic progenitors into
      peripheral blood of patients with multiple myeloma.
AB  - In this article, we review neoplastic contamination in the peripheral blood (PB)
      of patients with multiple myeloma (MM) upon stem cell mobilization. We first
      evaluated PB samples from pretreated MM patients following administration of high
      dose cyclophosphamide (Cy, 7 g/m2 or 4 g/m2) and granulocyte colony-stimulating
      factor (G-CSF) for the presence of myeloma cells as well as hematopoietic
      progenitors. Plasma cells containing intracytoplasmic immunoglobulin (cIg) were
      counted by immunofluorescence microscopy after incubation with appropriate
      antisera against light and heavy chain Ig. Flow cytometry studies were performed
      to determine the presence of malignant B lineage elements, using monoclonal
      antibodies against the CD19 antigen and the monotypic light chain. Prior to PBSC
      mobilization, circulating plasma cells were detected in all MM patients at 0.1%
      1.8% of the mononuclear cell (MNC) fraction (mean value 0.7 +/- 0.4% SD). In
      these patients, a higher absolute number of PB neoplastic cells was detected
      after administration of chemotherapy and G-CSF. Kinetic analysis showed a pattern
      of tumor cell mobilization similar to that of normal hematopoietic progenitors,
      with the peak coinciding with the optimal period for the collection of PBSC. The
      absolute number of plasma cells showed a 10-50-fold increase over the baseline
      value. Apheresis products contained 0.7 +/- 0.2% SD myeloma cells (range 0.2%
      2.7%), which demonstrated the capacity of plasma cells to proliferate,
      differentiate, and mature in response to c-kit ligand (SCF), IL-3, IL-6, and a
      combination of IL-3 and IL-6. Subsequently, in an attempt to reduce tumor cell
      contamination prior to autologous transplantation, circulating hematopoietic
      CD34+ cells were highly enriched by avidin-biotin immunoabsorption,
      cryopreserved, and used to reconstitute bone marrow (BM) function after
      myeloablative therapy in 13 patients. The median purity of the enriched CD34+
      cell population was 89.5% (range 51%-94%), with a 75-fold enrichment compared
      with the pretreatment samples. The median overall recovery of CD34+ cells and CFU
      GM was 58% (range 33%-95%) and 45% (range 7%-100%), respectively. Positive
      selection of CD34+ cells resulted in 2.5-3 log depletion of plasma cells and CD
      19+ B lineage cells as determined by immunofluorescence studies, although DNA
      analysis of the CDR III region of the IgH gene demonstrated the persistence of
      minimal residual disease (MRD) in 5 of 6 patient samples studied. Myeloma
      patients were reinfused with enriched CD34+ cells after myeloablative therapy
      consisting of total body irradiation (TBI, 1000 cGy) and high-dose melphalan (140
      mg/m2) or melphalan (200 mg/m2) alone. They received a median of 5 x 10(6) CD34+
      cells/kg and showed a rapid reconstitution of hematopoiesis. The median time to
      0.5 x 10(9) neutrophils, 20 x 10(9) and 50 x 10(9) platelets/L of PB was 10, 11,
      and 12 days, respectively. These results, as well as other clinically significant
      parameters, did not significantly differ from those of patients (n = 13)
      receiving unmanipulated PBSC following the same pretransplant conditioning
      regimen. Our data demonstrate the concomitant mobilization of tumor cells and
      hematopoietic progenitors in the PB of MM patients. Positive selection of CD34+
      cells reduces the contamination of myeloma cells from the apheresis products up
      to 3 log and provides a cell suspension capable of restoring normal hematopoiesis
      following a TBI-containing conditioning regimen.

PMID- 8877710
TI  - Granulocytes harvested following G-CSF-enhanced leukocyte recovery retain their
      functional capacity during in vitro culture for 72 hours.
AB  - The purpose of this study was to compare two different in vitro culture
      conditions for the preservation of human granulocytes. These cells could be used
      in patients with severe neutropenia following cytotoxic chemotherapy if the
      functional capacity was retained, and autologous transfusions of granulocytes
      would circumvent the risk of alloimmunization. Granulocytes were obtained from
      the peripheral blood of healthy donors and patients with hematologic malignancies
      who received cytotoxic chemotherapy supported by recombinant human granulocyte
      colony-stimulating factor (R-metHuG-CSF, 300 micrograms/day, s.c.). Granulocytes
      were either cultured for 72 h at 4 degrees C in the presence of 100 ng/ml G-CSF
      or cryopreserved at -196 degrees C. The viability, surface antigen expression,
      and function of the granulocytes were assessed. Since effective microbial killing
      involves the attachment of granulocytes to blood vessel walls, transmigration
      into tissues, chemotaxis, and phagocytosis, the surface expression of the
      adhesion molecules LFA-1 (CD11a/CD18) and gp 150,95 (CD11c/CD18) was measured. In
      addition, the IgG receptors Fc gamma RI (CD64), Fc gamma RII (CD32), and Fc gamma
      RIII (CD16), as well as the complement receptor CR3 (CD11b/CD18), were assessed.
      Dynamic superoxide anion release served as a measure of the metabolic pathway of
      the oxidative burst after f-Met-Leu-Phe (fMLP) and phorbol-12-myristate-13
      acetate (PMA) stimulation. Substantial differences in the preservation of
      granulocyte integrity and function were observed between the two storage
      conditions. Cryopreservation abolished reactivity to extracellular stimuli and
      severely affected the cell phenotype. On the other hand, functional activity
      could be maintained for up to 72 h when in vivo primed granulocytes of patients
      were incubated at 4 degrees C in the presence of G-CSF. This storage modality may
      permit the use of granulocyte autotransfusion to reduce the risk of neutropenic
      fever.

PMID- 8877711
TI  - Detection of minimal disease in patients with solid tumors.
AB  - The detection and elimination of minimal systemic disease in patients with solid
      tumors is one of the main current topics in clinical oncology. The present review
      focuses, therefore, on new diagnostic approaches to identify minimal disease in
      peripheral blood, bone marrow, and lymph nodes of patients with epithelial cancer
      as the major type of solid tumors in Western industrialized countries. These
      approaches may be used to improve tumor staging and monitoring of adjuvant
      therapies, as well as to detect tumor cell contamination in autologous stem cell
      grafts. Most investigators have developed either immunocytochemical assays with
      monoclonal antibodies to a variety of epithelial-specific cytoskeleton and
      membrane antigens or molecular methods based on the extensive amplification of a
      specific (c)DNA sequence by the polymerase-chain reaction (PCR). In
      immunocytochemical assays, antibodies to cytokeratins can be regarded as the most
      specific and sensitive probes to detect isolated epithelial tumor cells in bone
      marrow and blood. Molecular methods are based on the detection of either
      mutations in oncogenes and tumor suppressor genes (e.g., ki-ras and p53 genes) or
      the mRNA expression of tissue-specific and tumor-associated genes. mRNA species
      targeted in these assays encode cytokeratins, prostate-specific antigen, prostate
      specific membrane antigen, carcinoembryonic antigen, and polymorphic-epithelial
      mucin. To introduce the available methods into clinical practice, standardized
      protocols need to be developed and validated in multi-center studies.

PMID- 8877712
TI  - Hematopoietic stem cell emergence in embryonic life: developmental hematology
      revisited.
AB  - In utero, hematopoiesis takes place initially in the extraembryonic yolk sac,
      then switches to the liver, thymus, and, finally, bone marrow. This chronologic
      sequence and the fact that all blood-forming tissues but the yolk sac sustain
      hematopoiesis after colonization by stem cells of external origin have led to the
      hypothesis that the whole prenatal and postnatal blood system is founded by yolk
      sac-derived stem cells. Experimental data recently obtained from bird and mouse
      embryo models strongly suggest, however, that definitive hematopoiesis is
      established from an intraembryonic source of stem cells arising in the vicinity
      of the developing aorta. In agreement, an abundant population of CD34+ primitive
      hematopoietic cells has been identified in the equivalent area of the human
      embryo. These novel findings will contribute to our understanding of blood cell
      homeostasis and may help to further develop therapeutic protocols making use of
      fetal hematopoietic cells transplanted in utero or in postnatal life.

PMID- 8877713
TI  - Human-mouse xenografts in stem cell research.
AB  - New progenitor cell transplantation strategies that change the composition of the
      graft, such as CD34+ cell selection, ex vivo expansion, and gene marking, are
      budding. The efficiency and safety of most techniques are evaluated by in vitro
      assays using human progenitor cells and murine intraspecies transplantation
      studies before clinical introduction. However, proliferation potential in culture
      and engraftment capability can be discrepant. Furthermore, some CD34 epitopes and
      cytokines are unique to humans, thus rendering clinical inferences from
      experimental results difficult. Therapeutic studies with malignant human
      hematopoietic cells also require appropriate models that take into account
      pharmacokinetics. Human-mouse interspecies progenitor cell grafts may allow us to
      bridge this gap. For engraftment of human cells, recipients need to be
      immunodeficient. The highest long-term engraftment rate of up to 96% was obtained
      following transplantation of peripheral blood progenitor cells into non-obese
      diabetic/severe combined immunodeficiency mice. Data obtained from several human
      mouse xenograft transplantation models are presented and discussed.

PMID- 8877714
TI  - rhG-CSF in healthy donors: mobilization of peripheral hemopoietic progenitors and
      effect on peripheral blood leukocytes.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16
      micrograms/kg/day was given to 9 healthy donors to recruit hemopoietic
      progenitors (HP) for allogeneic transplantation or donor leukocyte infusion. rhG
      CSF was administered s.c. for 5 days. No side effects were encountered except for
      moderate bone pain and lumbago. Mobilization was effective, reaching a peak
      median value of 187 x 10(3) CD34+ cells/ml (range 51.2-1127) and 2170 x 10(3)
      colony-forming units-granulocyte macrophage (CFU-GM)/ml (range 1138-4190). Peak
      values were obtained at a median of 4 days of rhG-CSF and represented,
      respectively, a 13-fold and a 37-fold increase from baseline values (p = 0.0007
      and p = 0.006). White blood cell (WBC) counts increased 6-fold from baseline
      values (p < 0.0007) and reached a median peak of 34 x 10(6)/ml (23.5-59).
      Polymorphonuclear (PMN), and mononuclear (MNC) cells increased 10-fold and 2
      fold, respectively (p = 0.0039 and p = 0.0026) and reached a median peak of 32.1
      x 10(6)/ml (18.2-52) and 4.42 x 10(6)/ml (3.14-12.42). Absolute lymphocyte and
      monocyte counts increased at peak day in all donors 1.5-fold and 5.7-fold from
      baseline values (p = 0.0017 and p = 0.0018). In 7 of 9 donors, lymphocyte subsets
      were analyzed in detail. CD3+ and CD19+ lymphocytes increased 1.5-fold and 3
      fold, respectively (p = 0.032 for both). NK and activated T lymphocytes doubled
      at a median of 4 days of rhG-CSF (p = 0.032 and p = NS, respectively). Similar
      changes were observed in lymphocytes collected in leukapheresis product. T helper
      and T suppressor subsets displayed a similar increase. Thus, besides the
      anticipated priming effect on HP and PMN, rhG-CSF in healthy donors produced an
      unexpected and still unexplained modification of lymphocyte subsets in peripheral
      blood.

PMID- 8877715
TI  - Improved priming for mobilization of and optimal timing for harvest of peripheral
      blood stem cells.
AB  - The time of stem cell harvest and the mobilization regimen may play important
      roles in terms of achieving adequate numbers of stem cells by leukapheresis. To
      optimize the timing of leukapheresis, we have determined simultaneously the
      number of CD34+ cells in the peripheral blood as well as in the leukapheresis
      product of 214 apheresis procedures performed in 66 unselected patients with
      malignant hematologic diseases and solid tumors. A significant correlation
      between the number of CD34+ cells in peripheral blood and the leukapheresis
      product (R = 0.8) was found. The presence of more than 20 x 10(3)/ml blood CD34+
      cells gave a sufficient yield (> or = 1.0 x 10(6) CD34+ cells/kg) in 81% of the
      cases. In an attempt to compare two priming regimens, we performed leukapheresis
      twice in 12 patients with stable disease. In the first sequence, stem cells were
      mobilized with rhG-CSF (10 micrograms/kg/day) alone and, in the second sequence,
      with cyclophosphamide (4 g/m2) plus rhG-CSF. A significantly higher yield of
      CD34+ cells and a better correlation between CD34+ cells in the peripheral blood
      and the leukapheresis product were found after priming with high-dose
      cyclophosphamide plus rhG-CSF, compared with priming with rhG-CSF alone. In a
      multivariate analysis, three factors were found to correlate with the yield of
      CD34+ cells, namely prior chemotherapy, bone marrow function, and the
      mobilization regimen. The use of cyclophosphamide priming improves CD34+
      mobilization, and the introduction of blood CD34+ level optimizes the timing for
      harvest of stem cells, which should be performed early during treatment of
      malignancies.

PMID- 8877716
TI  - Thrombocytopenia after high-dose chemotherapy and autologous stem cell
      transplantation: an unresolved problem and possible approaches to resolve it.
AB  - Prolonged thrombocytopenia is a frequent clinical problem in cancer patients
      undergoing high-dose chemotherapy and autologous transplantation. The use of GM
      CSF as an adjuvant to autologous bone marrow transplantation (ABMT) has
      significantly reduced the duration of neutropenia after high-dose chemotherapy
      but failed to accelerate platelet recovery in transplanted patients. The more
      rapid hematopoietic reconstitution obtained by autologous mobilized peripheral
      blood progenitor cell transplantation (PBPCT) after high-dose chemotherapy has
      resulted in its increasing use instead of ABMT. However, PBPCT does not always
      produce faster platelet engraftment after high-dose chemotherapy, and persistent
      thrombocytopenia remains a significant clinical problem in PBPC-transplanted
      patients. The duration of severe thrombocytopenia (requiring frequent platelet
      transfusions) until platelet recovery varies widely depending on the quality of
      the autograft and previous radiotherapy or chemotherapy. The median days to reach
      20,000/microliters platelets ranged from 10 to 32 days. Pilot clinical studies in
      which cancer patients were transplanted with enriched CD34+ cell autografts,
      obtained from G-CSF-mobilized PB, showed a similar platelet recovery after high
      dose chemotherapy but also wide variation among the patients. The median days to
      reach 20,000/microliters platelets ranged from 9 to 38 days. The dose of CFU-GM
      in the autograft has been identified as the best predictive factor for
      hematopoietic recovery (p < 0.0001) after high-dose chemotherapy and autologous
      PBPCT in 118 patients with hematologic malignancies. A similar assessment of the
      megakaryocyte progenitor cells (BFU-MK and CFU-MK) in the autograft not only
      could predict time to platelet recovery but also could help to optimize the
      number and method of mobilization of the PBPC required to shorten the problematic
      obligatory 2-week duration of thrombocytopenia after high-dose chemotherapy. A
      routine assessment of the number of BFU-MK and CFU-MK present in each autograft
      and correlation with platelet recovery after transplantation would enable us to
      define the clinical threshold cell dose required for rapid platelet recovery.
      Recently, several non-specific cytokines with thrombopoietic activity have been
      evaluated in phase I clinical trials, including interleukin-1, interleukin-3
      followed by GM-CSF, interleukin-6, and interleukin-11 in cancer patients, showing
      an encouraging trend toward a decrease in thrombocytopenia after chemotherapy.
      The recently cloned specific platelet cytokine, thrombopoietin, is currently
      undergoing phase I clinical studies, and the results are awaited with interest.

PMID- 8877717
TI  - High purity, recovery, and selection of human blood cells with a novel high
      gradient magnetic separator.
AB  - The selective isolation of cell subpopulations from previously cryopreserved
      human blood mononuclear cells was achieved magnetically using a novel, well
      characterized conical funnel filter containing a variety of ordered wire arrays.
      Tetrameric antibody complexes targeted against the CD8 antigen were used to bind
      colloidal superparamagnetic dextran-iron particles to the desired cells with very
      low nonspecific binding. The novel design of the filter was such that the
      retention of cells at zero magnetic field was on average 0.9%. After two
      successive magnetic separations, an average purity of 98% was obtained for the
      desired labeled cells. A third separation gave > 99% purity. Purity was affected
      by the unlabeled cells, which expressed high intercellular adhesion (0.5% of the
      total cells). The ultimate recovery of the labeled cells was limited by the
      degree of nonmagnetic labeling of the cells expressing very low levels of
      targeted antigen. Recoveries could be as low as 78%, depending on the donor. The
      separation system described was believed suitable for difficult large-scale
      separations, that is, cells expressing the CD34 antigen.

PMID- 8877718
TI  - Purging of tumor cells from leukapheresis products: experimental and clinical
      aspects.
AB  - Peripheral blood progenitor cell autografts are being used increasingly in
      conjunction with high-dose therapy of cancer patients, in the belief that these
      products have a low probability of containing tumor cells. However, recent
      findings demonstrate that tumor cell involvement is frequent in leukapheresis
      products. Although the clinical value of purging has not been clinically
      established by prospective randomized trials, several studies indicate that
      contaminating tumor cells in autografts contribute to relapse of the disease in
      the recipients. We describe our experimental and clinical experience in purging
      tumor cells from leukapheresis products. Based on our work with purging of
      lymphoma cells from bone marrow by the use of anti-B cell and anti-T cell
      antibodies and immunobeads, a purging procedure to deplete leukapheresis products
      of lymphoma cells has been developed. Moreover, we present data showing that
      breast cancer cells can be efficiently removed from leukapheresis products using
      antibreast cancer antibodies, either in combination with immunobeads or as
      immunotoxins. Our experience with enrichment of CD34 cells employing immunobeads
      in leukaphresis products from patients with breast cancer and lymphomas shows
      high purity and yield of CD34 cells. In spite of this, contaminating tumor cells
      can be observed, strongly suggesting that a combination of CD34 cell enrichment
      and a purging procedure might be warranted.

PMID- 8877719
TI  - The role of monoclonal antibody affinity in tumor immunotherapy evaluated in in
      vivo models for minimal residual disease.
AB  - To evaluate the role of affinity in monoclonal antibody (mAb)-mediated treatment
      of carcinomas, we compared the antibodies 17-1A and 323/A3 that bind with
      different affinities overlapping epitopes on the epithelial adhesion molecule Ep
      CAM. This comparison was performed in several models for minimal residual disease
      in mice grafted with Ep-CAM transfected B16 melanoma cells originating from
      C57BL/6 mice. These cells were either grafted subcutaneously or injected
      intravenously into nude BALB/c mice, or grafted subcutaneously in immunocompetent
      C57BL/6 mice. In the BALB/c subcutaneous model, significant therapeutic results
      (p < 0.05) compared with the control mAb were obtained with both mAbs 17-1A and
      323/A3. However, when treating lung metastases in nude BALB/c mice that had
      developed after intravenous injection of the B16/Ep-CAM tumor cells, only the
      high-affinity 323/A3 mAb could significantly (p < 0.05) reduce the number of
      metastases that appeared. In syngeneic C57BL/6 mice grafted subcutaneously with
      B16/ Ep-CAM cells, a single 323/A3 or 17-1A mAb injection had no effect, in
      contrast to that observed for the nude BALB/c mouse model. However, multiple
      injections of the 323/A3 mAb significantly (p < 0.005) reduced the mean tumor
      volume, although they did not prevent tumor development. The results show that in
      vivo antibody-mediated effector cell activation and subsequent tumor cell
      elimination is determined by mAb affinity and target antigen density. Therefore,
      treatment of minimal residual disease with high-affinity mAb 323/ A3 is expected
      to improve the clinical results obtained with mAb 17-1A.

PMID- 8877720
TI  - Redirecting circulating antibodies via ligand-hapten conjugates eliminates target
      cells in vivo.
AB  - The elimination of cell populations in vivo often relies on reagents that are
      self-limiting, are difficult to design and produce or contain highly toxic
      components. Here we describe a novel immunotherapy using molecules that combine a
      cell-specific ligand and a hapten binding to preexisting antibodies in serum. The
      F(ab')2 fragment of a polyclonal anti-thymocyte globulin (ATG) preparation was
      used as a T-cell-specific ligand, and fluorescein isothiocyanate (FITC), as the
      hapten. Clearance of ligand-hapten conjugates from the circulation through
      formation of immune complexes was prevented through controlled synthesis of
      conjugates so that they contained one F(ab')2 fragment and one FITC molecule.
      Administration of a single dose of F(ab')2 or F(ab')2ATG-FITC into naive mice had
      no effect on the number of circulating T cells. In contrast, injection of
      F(ab')2ATG-FITC into mice with circulating anti-FITC antibodies resulted in the
      elimination of peripheral T cells. The reduction in cell numbers was equivalent
      to that obtained with a corresponding dose of intact ATG. Experiments in
      thymectomized mice demonstrated that the reduction of circulating T cells was due
      to target-cell elimination and not to immunomodulation or cellular sequestration.
      The adaptability of the model to other sources of effector antibodies and more
      useful ligands is discussed.

PMID- 8877721
TI  - Differential anti-MART-1/MelanA CTL activity in peripheral blood of HLA-A2
      melanoma patients in comparison to healthy donors: evidence of in vivo priming by
      tumor cells.
AB  - MART-1 is expressed ir both normal and neoplastic cells of melanocytic origin.
      Peripheral blood mononuclear cells (PBMC) from melanoma patients recognize and
      lyse tumor cells after repetitive in vitro stimulation with the immunodominant
      peptide MART-1(27-35). In this study, we compared the characteristics of the
      cytotoxic T lymphocyte (CTL) response to MART-1 in PBMC from 13 HLA-A2 melanoma
      patients with PBMC from 9 normal healthy donors stimulated in vitro with MART
      1(27-35) (AAGIGILTV) or FluM1(58-66) (GILGFVFTL) peptides. The expansion rate
      among CTLs from different patients was variable and did not correlate with the
      development of specificity against the MART-1(27-35) or FluM1(58-66) peptides.
      Specific anti-MART-1(27-35) cytotoxicity could be generated in 13 of 13 melanoma
      patients but only in 5 of 9 healthy donors (p < 0.001). Anti-FluM1(58-66)
      activity could be generated in six of seven melanoma patients and six of seven
      healthy donors. Specific activity against MART-1(27-35), but not FluM1(58-66),
      was detectable significantly earlier after repetitive in vitro stimulation in
      melanoma patients (22.7 +/- 2.0 days compared with 32.7 +/- 1.7 days for healthy
      donors, p < 0.01). This report provides the first evidence of an enhanced level
      of sensitization of tumor-bearing hosts compared with normal individuals against
      a differentiation antigen shared by tumor and normal cells of the same lineage.
      These findings may have important implications for delineating events involved in
      the biology of tumor rejection naturally or in response to active specific
      immunotherapy.

PMID- 8877722
TI  - Systemic interleukin-2 modulates the anti-idiotypic response to chimeric anti-GD2
      antibody in patients with melanoma.
AB  - The induction of human antimouse antibodies (HAMA) and human anti-idiotypic (anti
      Id) responses in cancer patients receiving therapeutic monoclonal antibody (mAb)
      may limit the effectiveness of the administered mAb. This report evaluates the
      influence of systemic interleukin-2 (IL-2) on the anti-Id response to anti
      disialoganglioside (anti-GD2) antibody given as treatment for patients with
      melanoma. Twenty-eight patients with melanoma received combined immunotherapy
      with anti-GD2 antibody and IL-2 at 1.5 x 10(6) U/m2/day given 4 days/week. The
      anti-GD2 antibody [murine 14.G2a mAb; dose levels of 2-5 mg/m2/day (4 patients);
      or human-mouse chimeric 14.18 (ch14.18) antibody; dose levels of 2-10 mg/m2/day
      (24 patients)] was scheduled to be given for 5 days either before, during, or
      after initial systemic IL-2 treatment. All four patients who received murine
      14.G2a developed HAMA anti-isotype antibodies (660-1,000 ng/ml) as well as
      measurable anti-Id antibodies. All three patients who received initial treatment
      with ch14.18 alone developed a strong anti-Id antibody response after IL-2 was
      started 1 week later. The serum level of anti-Id antibody decreased during
      subsequent ch14.18 infusions, suggesting that the anti-Id antibody may be binding
      the administered ch14.18. In contrast, measurable anti-Id antibody was detected
      in only 3 of 14 patients who received IL-2 before, during, and after initial
      ch14.18 administration. Two of four patients receiving systemic IL-2 before and
      during initial ch14.18 infusions, and two of three patients receiving systemic IL
      2 concurrent with initial ch14.18 infusions developed anti-Id antibodies. These
      data suggest that the anti-Id response to chimeric anti-GD2 antibody is
      influenced by the timing of systemic IL-2 in relation to antibody administration
      and can be suppressed by systemic treatment with IL-2 given before, during, and
      after the antibody administration.

PMID- 8877723
TI  - Influence of interleukin-2 regimens on circulating populations of lymphocytes
      after adoptive transfer of anti-CD3-stimulated T cells: results from a phase I
      trial in cancer patients.
AB  - The adoptive transfer of anti-CD3-stimulated T killer (T-AK) cells was tested
      with different bolus and infusional interleukin-2 (IL-2) regimens, and anti-CD3
      stimulation procedures to determine immunologic and antitumor effects in patients
      with a variety of advanced cancers. Indium-111 labeling was used to observe
      traffic patterns of the infused T-AK. Autologous peripheral blood mononuclear
      cells were obtained by leukapheresis. Cyclophosphamide (300 mg/m2) was given to
      most patients immediately after leukapheresis. The harvested cells were activated
      ex vivo with anti-CD3 overnight or for 4 days, at which time cells were reinfused
      and an IL-2 regimen was begun. Treatment was repeated 28 days later. This
      treatment regimen induced significant increases in leukocytes, lymphocytes, and
      eosinophils in patients in most treatment cohorts. Circulating lymphocytes were
      predominantly CD3+ T cells with preferential expansion of the CD8+ subset.
      Patients receiving cells stimulated in vitro for 4 days had significant T-cell
      lymphocytosis with either infusional or bolus plus infusional IL-2 regimens. T
      cell viability was decreased in culture after a second 4-day stimulation with
      anti-CD3 at day 28; this decrease could be prevented by adding IL-2 to the
      culture media. Cells stimulated overnight required both bolus and infusional IL-2
      to show an atypical lymphocytosis in vivo. Overnight-stimulated T-AK did not show
      decreases in in vitro viability at the day 28 restimulation. Indium-III-labeled
      cells trafficked to the liver, spleen, and bone marrow. No increase in uptake was
      observed in tumor deposits. There were 2 patients with partial responses, 5 with
      minor responses, 19 with stable disease, and 88 with progressive disease. The
      length of in vitro anti-CD3 stimulation, and the dose and timing of IL-2
      administration in vivo results in different circulating leukocyte populations
      after adoptive T-AK infusion. Generally, the CD8+ T-cell subset was
      preferentially expanded by this treatment approach. Repeated ex vivo stimulation
      with anti-CD3 may cause cell death.

PMID- 8877724
TI  - Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with
      metastatic breast cancer by pretreatment with low-dose intravenous
      cyclophosphamide.
AB  - THERATOPE (Biomira Inc., Edmonton, AB, Canada) STn-KLH cancer vaccine induces
      strong antibody titers against both the synthetic STn epitope and against a
      natural mucin, OSM, which expresses STn-like epitopes. In prospective, randomized
      studies in patients with metastatic breast cancer treated at two cancer centers,
      the effect of different low-dose, immunomodulatory cyclophosphamide (cyclo)
      pretreatments on the response to THERATOPE STn-KLH was compared. Patients were
      randomized to receive either intravenous cyclo 300 mg/m2 on day -3, or oral cyclo
      50 mg daily from days -14 to -3 inclusive, or no cyclo, before THERATOPE
      treatments. The anti-STn and anti-OSM antibody titers were higher in the patients
      who received cyclo intravenously before THERATOPE. Patients treated with cyclo
      intravenously and THERATOPE STn-KLH cancer vaccine lived significantly longer
      (projected median survival of 19.7 months versus actual median survival of 12.6
      months, p = 0.0176) than those treated with the same STn vaccine with oral or no
      cyclo. Although it is not clear how the anti-STn antibody response modifies tumor
      biology, we noted that patients in the intravenously administered cyclo group had
      a lower percentage of patients showing progressive disease at 9 weeks, and that
      there was an inverse correlation between serum anti-STN antibody titer and growth
      of measurable tumors. There was no correlation between tumor growth and anti-KLH
      antibody titers. These data are consistent with a therapeutic effect of THERATOPE
      STn-KLH cancer vaccine and support development of a phase III study to explore
      this further.

PMID- 8877725
TI  - Regulation of interferon-gamma gene expression.
AB  - Interferon-gamma (IFN-gamma), also known as type II interferon, is an important
      immunoregulatory gene that has multiple effects on the development, maturation,
      and function of the immune system. IFN-gamma mRNA and protein are expressed
      predominantly by T cells and large granular lymphocytes. The IFN-gamma mRNA is
      induced/inhibited in these cell types by a wide variety of extracellular signals,
      thus implicating a number of diverse, yet convergent signal transduction pathways
      in its transcriptional control. In this review, I describe how DNA methylation
      and specific DNA binding proteins may regulate transcription of the IFN-gamma
      gene in response to extracellular signals.

PMID- 8877726
TI  - Identification of single amino acid residues of human IL-6 involved in receptor
      binding and signal initiation.
AB  - The pleiotropic cytokine interleukin-6 (IL-6) has been predicted to be a protein
      with four antiparallel alpha-helices. On target cells, IL-6 interacts with a
      specific ligand binding receptor subunit (IL-6R), and this complex associates
      with the signal-transducing subunit gp130. Human IL-6 acts on human and murine
      cells, whereas murine IL-6 is only active on murine cells. The construction of
      chimeric human/murine IL-6 proteins has allowed us to define a region (residues
      77-95, region 2c) within the human IL-6 protein that is important for IL-6R
      binding and a region (residues 50-55, region 2a2) that is important for IL-6R
      dependent gp130 interaction. Guided by sequence alignment and molecular modeling,
      we have constructed several IL-6 variants with point mutations in these regions
      and have tested them for receptor binding and signal initiation. Within region
      2c, phenylalanine 78 was involved in receptor binding, whereas lysine 54 within
      region 2a2 participated in gp130 activation. Furthermore, some IL-6 variants with
      lysine 54 replacements could be used to construct muteins that retained receptor
      binding but failed to activate gp130. Such IL-6 muteins were efficient IL-6
      receptor antagonists.

PMID- 8877728
TI  - Cryoglobulinemia in hepatitis C virus chronic active hepatitis: effects of
      interferon-alpha therapy.
AB  - We investigated the prevalence of mixed cryoglobulinemia (MC) in 100 cases of
      chronic hepatitis C virus (HCV) infection and the effect of a 6-month treatment
      with interferon-alpha (IFN-alpha). Cryoglobulins were detected on admission in 36
      of 100 patients and appeared during observation in a further 18 cases. Cryocrit
      ranged from 0.5% to 20%. Patients with MC were older and had a higher incidence
      of cirrhosis than those without MC. Immunologic characterization of the
      cryoprecipitate showed the presence of type II in 84% of cases and type III in
      16%. The patients received IFN-alpha (6 MU three times per week) for 6 months.
      Fifty-seven were responders (i.e., reached normal aminotransferase levels), 26 of
      these relapsed within 2 months after IFN withdrawal, and 30 did not relapse.
      After IFN-alpha treatment, cryoglobulinemia disappeared in 11 of the 21 evaluable
      responders, but in none of the 15 nonresponder patients (p < 0.003). The
      clearance of MC was associated in all cases with clearance of HCV RNA. The
      delayed appearance of cryoglobulinemia in responders seems to be associated with
      a higher probability of relapse.

PMID- 8877727
TI  - Interferon-beta prevents the upregulation of interleukin-8 expression in human
      melanoma cells.
AB  - The constitutive expression of interleukin-8 (IL-8) by human melanoma cells
      correlates with their metastatic potential. The exposure of human melanoma cells
      to the inflammatory cytokines IL-1 beta or tumor necrosis factor-alpha (TNF
      alpha) upregulated IL-8 expression in a time-dependent and concentration
      dependent manner. This enhanced expression of IL-8 was inhibited by cycloheximide
      or actinomycin-D. Treatment of melanoma cells with interferon (IFN) alpha, beta,
      or gamma did not affect the constitutive expression of IL-8, but IFN-alpha and
      IFN-beta blocked the upregulation of IL-8 expression in cells treated with IL-1
      beta or TNF-alpha subsequent to or simultaneously with the IFN. These data
      suggest that the expression of IL-8 in human melanoma cells can be upregulated by
      inflammatory cytokines and that IFN-alpha and IFN-beta can counterregulate this
      stimulation.

PMID- 8877729
TI  - Correlation of interleukin-6 gene expression to immunologic features in patients
      with cardiac myxomas.
AB  - Cardiac myxomas, the most common primary heart tumors in adults, show a variety
      of clinical manifestations and laboratory findings correlated with elevated
      interleukin-6 (IL-6) serum concentration. The aim of this study was to determine
      the expression of IL-6 mRNA in myxoma tissue as a cause to frequent immunologic
      abnormalities in patients with such tumors. In our centers, we analyzed 17
      surgically resected myxomas using the polymerase chain reaction (PCR) and found
      increased IL-6 mRNA expression in 14 of 17 cases. The serum IL-6 levels of the 14
      patients, detected by enzyme-linked immunosorbent assay (ELISA) with mouse
      antihuman monoclonal antibody (mAb), were high preoperatively (> 6 pg/ml) and
      decreased to normal postoperatively (< or = 6 pg/ml). These same 14 patients
      exhibited significant autoimmune disorders preoperatively. The other 3 patients
      had normal serum levels of IL-6 (< or = 6 pg/ml) and did not present any serious
      signs and symptoms, and molecular analysis did not show overexpression of IL-6
      mRNA in neoplasmic tissue. These results suggest that IL-6 is overproduced in
      myxoma tissue and secreted into the systemic circulation as a stimulator of the
      immunoregulatory system. Furthermore, this study indicates the promising role of
      molecular biology techniques in the research of pathophysiologic mechanisms of
      cardiac myxomas.

PMID- 8877730
TI  - Repression of interleukin-2 and interleukin-4 promoters by tumor suppressor
      protein p53.
AB  - Interleukin 2 (IL-2) and interleukin 4 (IL-4) secreted by activated but not by
      resting mature T cells are pleiotropic cytokines affecting growth and
      differentiation of diverse cell types, such as T cells, B cells, and mast cells.
      There is little information about the molecular basis for the constitutive
      repression of IL-2 and IL-4 gene expression in unstimulated T cells. We
      investigated the possibility that wild-type (wt) p53, a nuclear tumor suppressor
      protein, might serve to repress IL-2 and IL-4 gene expression in murine E14 T
      lymphoma and in human Jurkat cells. We transiently cotransfected these cells with
      constitutive simian virus 40 (SV 40) early promoter expression plasmids
      overproducing wt or mutant murine p53 and with appropriate luciferase (luc)
      reporter plasmids containing the promoter elements of murine IL-2 and IL-4 genes
      to evaluate the effect of various p53 species on these promoters. Murine wt p53
      derived from pSG5p53cD strongly repressed the IL-2 and IL-4 promoters in both
      cell lines induced by the phorbol ester TPA and the Ca2+ ionophore ionomycin but
      not, however, in uninduced cells. In similar transient transfection experiments
      with lymphoma cells, overexpression of deletion mutant species of murine p53
      revealed that the N-terminal and C-terminal domains are crucial for inhibition of
      both IL-2 and IL-4 gene expression. These parts of p53 comprise the
      transactivation domain at the amino terminal side, which has previously also been
      shown to interact with the TATA-box binding-protein TBP and the carboxy-terminal
      oligomerization domain. Additionally, it was shown that a previously described
      inhibitory protein, the high-mobility-group protein HMG-I/Y, does not
      functionally interact with p53. Cotransfection of expression plasmids for both
      p53 and HMG-I/Y did not alter the extent of inhibition by the individual
      proteins. These data suggest that p53 can downmodulate both IL-2 and IL-4 gene
      expression and that both the transactivation and oligomerization domains of the
      tumor suppressor protein are essential for this transcriptional repression.

PMID- 8877732
TI  - Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR + CD4-CD8-T
      cells.
AB  - A novel cytokine originally designated murine CTLA-8 was described as a cDNA
      isolated from an activated T cell hybridoma produced by fusing a mouse cytotoxic
      T cell clone and a rat T lymphoma. This cDNA, which contains mRNA instability
      sequences characteristic of many cytokines, encoded a putative secreted protein
      that was homologous to the ORF13 gene of Herpesvirus saimiri. The human homolog
      to this molecule has recently been identified as the proinflammatory cytokine IL
      17. We describe the isolation of a cDNA encoding mouse IL-17 from a cDNA library
      generated from alpha beta TCR + CD4-CD8- thymocytes using a subtraction technique
      that enriched for activation specific genes. This cDNA shares 87.3% amino acid
      identity to the previously described murine CTLA-8. Comparison of murine CTLA-8
      to a cDNA we isolated from activated rat splenocytes revealed that murine CTLA-8
      is, in fact, the rat homolog of IL-17. Mouse IL-17 mRNA is specifically expressed
      by activated alpha beta TCR + CD4-CD8- T cells, a small subset with a potentially
      important role in immune regulation. Mouse, rat, and human IL-17 can induce IL-6
      secretion in mouse stromal cells, indicating that all homologs can recognize the
      mouse receptor.

PMID- 8877731
TI  - Mechanisms in interleukin-2 protection against glucocorticoid-induced apoptosis:
      regulation of AP-1 and glucocorticoid receptor transcriptional activities.
AB  - We have used the gibbon ape leukemia cell line MLA-144 and its corticoid
      sensitive subclone MLA-E7T to analyze the mechanisms whereby interleukin-2 (IL-2)
      can protect T cells against dexamethasone-induced apoptosis. MLA cells are
      characterized by the constitutive expression of intermediate affinity receptors
      for IL-2, together with IL-4 receptors. MLA-144 cells secrete IL-2 and are
      insensitive to dexamethasone, whereas MLA-E7T cells do not constitutively produce
      significant amounts of IL-2 and undergo apoptotic cell death in the presence of
      dexamethasone. Exogenous IL-2 was shown to protect MLA-E7T cells against the
      apoptotic effect of dexamethasone and to increase both the DNA binding and
      transactivating functions of activator protein-1 (AP-1). The functional
      relationship between AP-1 and glucocorticoid receptors transcriptional activities
      was further investigated using transient expression of reporter gene constructs
      whose transcriptions are regulated by promoters containing TPA-responsive
      elements or glucocorticoid-responsive elements. The data reported here
      demonstrate that in MLA-144 cells, IL-2 or PMA stimulation antagonizes the
      glucocorticoid receptor, whereas in MLA-E7T, synergistic effects are observed
      between dexamethasone and IL-2 or PMA for transactivation of MMTV-CAT. Taken
      together with the finding that IL-2 but not PMA protects MLA-E7T from
      dexamethasone-induced apoptosis, our results indicate that IL-2 does not induce
      such a protection by repressing the transcriptional activity of the
      glucocorticoid receptor.

PMID- 8877733
TI  - The effect of interferon-alpha on the pituitary-adrenal axis.
AB  - This report concerns the use of a minimum stress animal model for evaluating the
      neuromodulatory effects of interferon-alpha (IFN-alpha). Male Sprague-Dawley
      rats, 350-450 g, received jugular catheters and were habituated to handling and
      sampling arenas. These procedures will minimize stress usually associated with
      i.v. injections and blood sampling. Natural rat IFN-alpha/beta (RaIFN-alpha/beta)
      endotoxin free (Lee Biomolecular Research Laboratories, San Diego, CA) or
      recombinant human IFN-alpha, (rHuIFN-alpha) (a gift from Hoffman La Roche,
      Nutley, NJ) was injected into rats via catheter at various IFN concentrations.
      Controls were injected with either (1) vehicle (saline), (2) human or bovine
      serum albumin in saline, or (3) heat-denatured RaIFN-alpha/beta. Experiments were
      begun (0 h) at about 0900 h, and blood samples were withdrawn at intervals up to
      2 h after IFN or control injections and replaced by the same volume of saline.
      The concentrations of corticosterone and ACTH in peripheral plasma were measured
      by radioimmunoassay. Both IFN, when injected at concentrations of 300 or 600 U/g
      body weight (U/gbw), stimulated an increase above 0 h levels of both hormones in
      the same animals. Additionally, the stimulation was also evident when compared
      with plasma hormone levels in animals injected with control substance in a
      parallel time course. After administration of 150 U/gbw of either IFN, only the
      increase in the blood corticosterone was significant. These studies demonstrate
      that both homospecific (RaIFN-alpha/beta) and heterospecific (rHuIFN-alpha) IFN
      preparations are capable of stimulating the pituitary-adrenal axis.

PMID- 8877734
TI  - Phase I/IB study of polyadenylic-polyuridylic acid in patients with advanced
      malignancies: clinical and biologic effects.
AB  - The synthetic polynucleotide polyadenylic-polyuridylic acid (polyA:polyU) has
      shown antitumor activity in murine studies and human breast cancer. PolyA:polyU
      was evaluated in 25 cancer patients receiving weekly intravenous doses between 3
      and 600 mg/m2. PolyA:polyU was well tolerated up to 600 mg/m2, with no
      doselimiting toxicity (all < grade 3). Side effects included mild elevation in
      temperature, fatigue, and mild hyperglycemia. No changes outside of the normal
      range in hematocrit, WBC count, platelet count, total bilirubin, or alkaline
      phosphatase were observed. Of 25 patients, 18 completed at least one cycle of 6
      weeks, and 5 completed two cycles (median 6 weeks). Four patients had stable
      disease over 11-13 weeks of treatment, and no clinical responses were observed.
      At 24 h after the first treatment, there were no significant increases in
      biologic response (beta 2-microglobulin and neopterin in serum, or 2',5'
      oligoadenylate synthetase in peripheral blood mononuclear cells). A small
      increase in beta 2-microglobulin was observed 24 h after the week 3 treatment
      (1.1-fold, p < 0.01). By the third week of treatment, 2-5A synthetase levels
      decreased slightly (to 80% of baseline, p < 0.01). No changes in cytokines IL-6,
      IL-12, tumor necrosis factor (TNF), or IL-2 receptor in serum were detected after
      24 h of treatment. Thus, at these doses, polyA:polyU had no marked modulation on
      biologic responses in vivo, although this preparation significantly induced 2-5A
      synthetase in peripheral blood mononuclear cells in vitro. PolyA:polyU was well
      tolerated. An MTD was not reached but was greater than 600 mg/m2 on this weekly
      schedule.

PMID- 8877735
TI  - The biological properties, assay, and standardization of interferon-alpha: a need
      for a WHO collaborative study.
AB  - Interferon-alpha (IFN-alpha) exists as a range of closely related, biologically
      active proteins and has been the subject of extensive research and clinical
      investigation. Standardization of IFN-alpha and the uniform reporting of IFN
      alpha activity in International Units (IU) is critical to preclinical research
      and the clinical development of IFN-alpha products as therapeutic agents.
      Currently, several different IFN-alpha-containing reference preparations,
      established as World Health Organization (WHO) International Standards (IS) for
      particular IFN-alpha proteins (mixtures or single molecular species) are
      available for assay calibration. Nevertheless, the heterogeneous nature of IFN
      alpha has raised standardization issues relating to the activity of individual
      IFN-alpha proteins, hence-forth termed subtypes, in the various biologic assays
      used for determining IFN-alpha levels. These issues include the question of
      parallelism of dose-response curves among particular IFN-alpha subtypes and
      different, naturally produced IFN-alpha subtype mixtures, for example, leukocyte
      IFN-alpha, and the applicability of IU of IFN-alpha activity defined by antiviral
      assays to alternative biologic assays, for example, antiproliferative assays. To
      address such issues, a WHO Consultative Group on Cytokine Standardization
      requested that the National Institute for Biological Standards and Control
      (NIBSC) and the Centre for Biologics Evaluation and Research (CBER) organize an
      international collaborative study to compare the activities and relative
      potencies of the several available IFN-alpha preparations, including those
      derived from human cells containing mixtures of IFN-alpha subtypes and those
      derived by rDNA methods containing single IFN-alpha subtypes, in different
      assays. To date, 111 participants in 32 countries have been recruited to the
      study and have agreed to assay a total of 17 different natural and recombinant
      IFN-alpha preparations or a defined subset thereof in specific in-house assays.
      The assay results generated will be statistically analyzed and evaluated to
      address the stated issues and to assess whether any individual IFN-alpha
      preparation is suitable to serve as an IS for all IFN-alpha preparations or
      whether more than one IS will be needed for this purpose.

PMID- 8877736
TI  - Laparoscopic herniorrhaphy versus traditional open repair at a community
      hospital.
AB  - Over a 2-year period 157 inguinal hernias in 151 patients were consecutively
      entered in this descriptive, observational study to determine any difference in
      outcome between a laparoscopic inguinal hernia repair versus an open inguinal
      hernia repair in a community hospital setting. The laparoscopic transabdominal
      preperitoneal technique was utilized in 50 cases. A conventional open repair was
      used in 107 cases. There were statistically significant differences when the
      laparoscopic and open groups were compared for the number of days until driving a
      car (p < 0.01), the number of days until getting in and out of bed comfortably (p
      = 0.01), the number of days until working on a limited basis (p = 0.01), and the
      number of days until working on a full-time basis (p < 0.05), although these
      differences may be due to confounding factors in this nonrandomized study. The
      average length of operating time was 72.2 min laparoscopic versus 51.6 min open
      (p < 0.001). We have shown that laparoscopic inguinal hernia repairs may have
      benefits over conventional hernia repairs. This may make its use more widespread
      than it has already become.

PMID- 8877737
TI  - Laparoscopic versus open inguinal herniorrhaphy: a critical appraisal.

PMID- 8877738
TI  - Laparoscopic-assisted surgery of the spleen: clinical experience in expanding
      indications.
AB  - Between January 1993 and November 1995 laparoscopic surgery was used in 21
      patients with a variety of splenic diseases, namely idiopathic thrombocytopenic
      purpura, congenital spherocytosis, lymphoma, leukemic infiltrative disease,
      splenic infarction, trauma, or splenic cyst. Total splenectomy was carried out
      laparoscopically in 16 patients. Conversion to open splenectomy was necessary in
      two other patients because of intractable bleeding. Two patients with a splenic
      cyst underwent laparoscopic unroofing of the cyst. Conservative hemostasis of a
      spleen injury grade II was carried out in a child after blunt trauma. The total
      mean duration of the laparoscopic procedures was 158 min and the mean blood loss
      volume was 350 ml, both conversions being excluded. Postsurgical recovery was
      excellent and the average hospital stay was 5 days, including the patients with
      conversion. There were no significant postoperative complications. Our
      observations indicate that an increasing number of surgical diseases of the
      spleen can be managed adequately by a less invasive laparoscopic approach.
      However, the criteria for using this procedure are in an expanding phase and are
      still mainly dependent on the surgeon's technical experience.

PMID- 8877739
TI  - Laparoscopic fundoplication.
AB  - Most reports on laparoscopic fundoplication are from large, tertiary referral
      medical centers. Presented here is an experience by a single surgeon (M.E.F.) in
      community hospitals with 74 cases. All patients had esophagitis. All but two
      patients were Visick grade IV off medication. All patients had an incompetent
      lower esophageal sphicter. Four with abnormally low esophageal contractions
      underwent a Toupet procedure; the rest had a Nissen fundoplication. The largest
      estimated blood loss was 300 cc. One case (1.4%) had to be converted
      intraoperatively to an open procedure because of bleeding from an iatrogenic
      liver laceration. There were two minor complications (a urinary tract infection
      and a pneumothorax) and one death (massive liver necrosis with an otherwise
      unremarkable post mortem, thus it was felt to be due to anesthesia). The mean
      length of hospital stay was 2.8 +/- 0.21 days. Eighty-nine percent of the
      operations totally relieved reflux. Nineteen patients (26%) had mild, early
      postoperative dysphagia, gas bloat, and/or early satiety. Four patients did not
      get any improvement in their reflux, three still require chronic medication, and
      one underwent a redo open fundoplication. Three early patients had severe, new
      onset postoperative dysphagia secondary to too tight a fundoplication. Attention
      must be focused on creating a loose wrap, a "floppy" Nissen by routine division
      of the short gastric vessels and the use of a large dilator in the esophagus when
      the fundoplication is constructed. Laparoscopic fundoplication is technically
      feasible, safe, and effective in a community hospital and does not require a
      large, tertiary referral medical center.

PMID- 8877740
TI  - Laparoscopic cholecystectomy in histologically confirmed acute cholecystitis.
AB  - Forty-four patients with histologically confirmed acute cholecystitis (AC)
      underwent attempted laparoscopic cholecystectomy (LC) from August 1990 to
      February 1994 and were retrospectively reviewed. During this time frame, LC was
      attempted in all patients with AC. Twelve of the patients were scheduled for
      elective LC as they were not thought to have AC preoperatively. Interestingly,
      eight of these unsuspected cases of acute cholecystitis had both a normal
      preoperative white blood cell count and were afebrile. The other 32 patients had
      a clinical presentation consistent with AC. The only diagnostic finding common to
      all cases of AC was abdominal pain and tenderness. In addition to AC, five
      patients also had gallstone pancreatitis, and three others were found to have
      concomitant choledocholithiasis. Fourteen patients required intraoperative
      conversion to open cholecystectomy for a laparoscopic success rate of 68%. The
      most common reason for conversion was difficulty in the dissection or unclear
      anatomy caused by dense adhesions. LC is an appropriate surgical treatment of AC,
      provided the surgeon abandons the laparoscopic approach if unable to safely
      proceed. Diagnostic and admission criteria for AC that requires elevated white
      blood cell count and/or fever may need revision.

PMID- 8877741
TI  - A prospective evaluation of an endoscopic ultrasonic probe to detect
      intraparenchymal malignancy at pediatric thoracoscopy.
AB  - Thoracoscopy has been proposed as the procedure of choice for the evaluation of
      focal, suspected malignant pulmonary lesions in children. One drawback with this
      approach, however, is the concern that intraparenchymal lesions may go
      undetected. We prospectively evaluated the ability of an endoscopic ultrasonic
      probe to detect intraparenchymal nodules. The handheld probe contains a
      piezoelectric ultrasound emitter and receiver that operates at 7.5 MHz. The axial
      resolution of the probe is 1.1 cm. Two different probe tips were used. One is a
      forward viewing tip and the other is angled at 45 degrees relative to the axis of
      the probe shaft. Both probes image 90 degrees sectors. Twelve thoracoscopies on
      nine patients were performed using the ultrasound probe. Of seven patients with
      confirmed metastatic disease, six had thoracoscopy converted to open thoracotomy
      to assure that no lesion had been missed. The probe was able to accurately assess
      surrounding bronchovascular structures and the presence and location of
      previously placed surgical clips. Although deep structures were readily
      visualized with the probe, lesions within 1.5 cm of the surface of the lung were
      poorly visualized. No complications occurred. This ultrasound system allows for
      the distinction of dense lesions from the surrounding pulmonary parenchyma except
      for those lying near the surface of the lung, which are usually easy to see
      directly. Furthermore, the images define the broncho vascular structures adjacent
      to the lesion. This device may enhance thoracoscopy by facilitating the detection
      of, and ability to resect, pulmonary intraparenchymal lesions.

PMID- 8877742
TI  - Technique of hand-assisted laparoscopic surgery.
AB  - Advanced laparoscopic techniques can be challenging to perform because tactile
      sensation is limited with available laparoscopic instrumentation. Described is a
      technique of placing the surgeon's hand into the peritoneal cavity while
      maintaining pneumoperitoneum. Use of the hand allows for easy exposure, complete
      exploration, meticulous dissection, and immediate hemostasis. Our experience
      reveals patients have a short hospital stay and recuperation time.

PMID- 8877743
TI  - Cholangiography for evaluation of the proximal biliary ducts in laparoscopic
      cholecystectomy.
AB  - Visualization of the entire biliary tree can be difficult in some patients
      undergoing cholangiography during laparoscopic cholecystectomy. A simple
      technique was developed for these patients, utilizing the laparoscope under
      fluoroscopic guidance, in order to visualize the proximal biliary ducts.

PMID- 8877744
TI  - Myocardial bridging prevents safe laparoscopy? A case report.
AB  - A 49-year-old male presented with atypical chest pain. Complete cardiac
      evaluation was normal except for cardiac catheterization, which revealed a
      myocardial bridge across the LAD (left anterior descending coronary artery) that
      caused a 50% systolic stenosis. Abdominal ultrasound revealed cholelithiasis. The
      patient became asymptomatic and was discharged only to return with biliary
      pancreatitis, which resolved over 2 weeks and laparoscopic cholecystectomy was
      attempted. Upon establishment of a pneumoperitoneum, he began to suffer cardiac
      ischemia, which immediately resolved upon desufflation. The procedure was
      converted to an uneventful open cholecystectomy. He did well without any further
      problems. This is the first report of myocardial bridging, a well-known cardiac
      anomaly, possibly preventing safe laparoscopy. This was possibly due to
      transmitted intraperitoneal pressure effect on the pericardium pushing closed
      that myocardial bridge.

PMID- 8877745
TI  - Laparoscopic Heller's cardiomyotomy and Dor's fundoplication for esophageal
      achalasia.
AB  - The study's aim was to assess the functional results of laparoscopically
      performed Heller's myotomy and Dor's fundoplication in our first few cases of
      esophageal achalasia. Four male patients (mean age: 61 years) with long-standing
      symptoms of achalasia (documented on esophagogram and esophageal manometry) and
      not responding to several sessions of pneumatic dilatation, had laparoscopic
      Heller's myotomy and Dor's fundoplication. Myotomy was facilitated by distending
      the esophagus. The mean duration of the operation was 99 min. The third patient
      developed a leak from the exposed esophageal mucosa on the 5th postoperative day
      while at home. The leak was attributed to late desloughing of a mucosal burn, and
      was sealed spontaneously 15 days later after drainage. The remaining three
      patients were discharged after resuming diet within the first 2 postoperative
      days. By 1 year postoperatively, dysphagia was abolished in all cases, and there
      were no gastroesophageal reflux symptoms. The esophagogram showed no reflux,
      which was also confirmed on ambulatory 24-h esophageal pH measurement. On
      manometry, lower esophageal sphincter (LES) pressure dropped significantly
      postoperatively (preop: 56 +/- 7 SD mm Hg, postop: 5 +/- 1 SD mm Hg, p < 0.001).
      In conclusion, laparoscopic Heller's myotomy with Dor's fundoplication for
      esophageal achalasia is a feasible procedure, offering clinical and laboratory
      results similar to the open approach, but with better patient tolerance.

PMID- 8877746
TI  - Laparoscopic repair of a traumatic lumbar hernia: a case report.
AB  - Lumbar hernia is an uncommon flank hernia and a rare complication of blunt
      trauma. We present a case of acute lumbar hernia as a direct result of blunt
      trauma. Traditionally, exploratory laparotomy with open repair is indicated, but
      we report a case of a traumatic lumbar hernia explored and repaired
      laparoscopically.

PMID- 8877747
TI  - Gasless laparoscopic resection of hepatocellular carcinoma (HCC) in cirrhosis.
AB  - Liver resection by open surgery remains the method of choice for treatment of
      hepatocellular carcinoma (HCC) in cirrhotic patients with compensated liver
      function. Laparoscopy for surgical treatment of hepatic diseases is at an early
      stage. Laparoscopy has been often proposed for diagnosis, staging of hepatic
      malignancy, treatment of hepatic cyst or benign tumors, but very few laparoscopic
      treatments of hepatic malignancies have been reported at present and always using
      conventional CO2 laparoscopy. We describe herein the operative treatment of a
      single subglissonian HCC of segment III in a child, HCV (hepatitis C virus)
      related cirrhosis. A nonanatomical wedge resection was performed by gasless
      laparoscopic technique using a mechanical retractor obviating the creation of the
      pneumoperitoneum and of the sealed environment. The technique, in selected cases,
      is a simple, safe, and effective surgical method. The gasless technique
      guarantees a clear vision, it makes possible the continuous suction of smoke and
      fluids, it allows the use of conventional instruments for classic maneuvers of
      the liver surgery (Pringle maneuver), and the easy management of suturing. The
      present case has proved to be another abdominal procedure that can be carried out
      with all the advantages of gasless minimally invasive surgery.

PMID- 8877748
TI  - Laparoscopic marsupialization of lymphocele after combined pancreas-kidney
      transplantation.
AB  - Early definitive treatment of symptomatic posttransplant lymphoceles offers good
      results with fewer graft losses and reduced morbidity. If interventional therapy
      fails, laparoscopic internal marsupialization to the peritoneal cavity may be
      performed with excellent results and at low cost. In combined pancreas-kidney
      transplantation the transperitoneal laparoscopic access may be difficult due to
      adhesions caused by the intraabdominal positioning of the pancreatic graft and
      posttransplantation pancreatitis. Both posttransplantation lavage of the
      abdominal cavity as well as immunosuppression reduce formation of intraabdominal
      adhesions subsequent to combined pancreas-kidney transplantation. Thus,
      posttransplant lymphoceles may be treated safely even after combined kidney
      pancreas transplantation.

PMID- 8877749
TI  - Laparoscopic oophorectomy in children by a multiple-trocar technique.

PMID- 8877750
TI  - A comparative study of linear and nonlinear simulations of the leaflets in a
      bioprosthetic heart valve during the cardiac cycle.
AB  - Two geometrically identical models of the leaflets of a bicuspid bioprosthetic
      heart valve have been constructed using finite elements. The boundary conditions
      applied to the models were also identical but a linear material model has been
      used in one and a nonlinear elastic model in the other. The models were fullscale
      and contained 2600 Belytschko-Lin-Tsai shell elements which allowed the variation
      of stress through the thickness of the leaflet to be modelled. A time-varying,
      spatially-uniform pressure differential was applied across the leaflets to model
      their behaviour during a complete cardiac cycle. The simulation was performed
      using a dynamic, explicit, time-stepping, finite element code. A comparison of
      the two models showed that the nonlinear model was more responsive to the time
      varying pressure wave, and deformed into more complex shapes during the opening
      and closing phases which induced lower compressive but higher tensile stresses in
      the leaflets.

PMID- 8877751
TI  - Comparison of three arterial pulse waveform classification techniques.
AB  - Peripheral pulse waveforms can become stretched and damped with increasing
      severity of peripheral vascular disease (PVD) and hence could provide valuable
      diagnostic information. This study compares the diagnostic performance of 3
      established classification techniques (a linear discriminant classifier, a k
      nearest neighbour classifier, and an artificial neural network) for the detection
      of lower limb arterial disease from pulse waveforms obtained using photoelectric
      plethysmography (PPG). Pulse waveforms and pre- and post-exercise Doppler
      ultrasound ankle to brachial pressure indices (ABPI) were obtained from patients
      attending a vascular measurement laboratory. A single PPG pulse from each big toe
      was recorded direct to computer, pre-processed, and then used as classifier input
      data. The correct classifier outputs were the corresponding ABPI diagnostic
      classification. Pulse and ABPI measurements from 100 legs were used as training
      data for each classifier, and the computed classifications for pulses from a
      further 266 legs were then compared with their ABPI diagnoses. The diagnostic
      accuracy of the artificial neural network (80%; was higher than for the optimized
      k-nearest neighbour classifier (k = 27, accuracy 76% and the linear discriminant
      classifier (71%). The Kappa measure of agreement which excludes chance was
      highest for the artificial neural network (57%) and significantly higher than
      that of the linear discriminant classifier (Kappa 40%, p < 0.05). The value of
      Kappa for the optimized k-nearest neighbour classifier (k = 27) was intermediate
      at 47%. This study has shown that classifiers can be taught to discriminate
      between small, and perhaps subtle, differences in features. We have demonstrated
      that artificial neural networks can be used to classify arterial pulse waveforms,
      and can perform better overall than k-nearest neighbour or linear discriminant
      classifiers for this application.

PMID- 8877752
TI  - New applications of electrical impedance of human blood.
AB  - The electrical impedance parameters of human blood, that is, plasma resistance
      Rp, cell interior resistance Ri and cell membrane capacitance Cm, were determined
      by measuring impedance amplitudes at three different frequencies, 0.1, 0.8 and
      1.2 MHz. Several new findings have been obtained. The fibrinogen in normal blood
      raised Rp and Cm by about 4% and 20%, respectively, and serum proteins
      contributed to the capacitance by about 14%. The results imply that the
      electrical impedance of blood may reflect certain diseases that involve abnormal
      compositions of certain plasma proteins. Measurement on 62 samples with various
      erythrocyte sedimentation rates (ESR) demonstrated that both Rp and Cm were
      proportional to ESR, implying that the impedance measurement might be an
      alternative method for quick estimation of ESR. During in vitro storage of blood
      at 4 degrees C, both Rp and Cm decreased with time, about -20% for Cm after four
      weeks of storage. The results imply that the impedance change might be a useful
      index for evaluating the quality of stored blood.

PMID- 8877753
TI  - A needle type therapeutic system incorporating laser light and lumin for
      immunotherapy of cancer growing in deep organs.
AB  - Lumin is a potent cell-activating agent and a photosensitizer characterized by
      absorption peaks at 670 nm and 770 nm. It has already been demonstrated that
      macrophase activity is enhanced greatly by lumin administration with laser light
      irradiation and that this method is useful in cancer immunotherapy. In this
      study, a new needle type therapeutic system was developed for the immunotherapy
      of cancer growing in deep human organs. A human lung cancer grafted onto nude
      mice was strongly cicatrized by collagen fibres about four weeks after the first
      treatment. The collagen fibres seemed to seal-off the tumor and prevent its
      growth with intense cicatrization. In addition, a high T/B cell ratio of
      lymphocytes was observed in the peripheral blood of the treated mice, although
      the thymus is congenitally absent from nude mice. These results demonstrated that
      the system is a reliable method for cancer treatment in deep organs without side
      effects and/or major surgical intervention.

PMID- 8877754
TI  - Stray RF field strength during radiofrequency endometrial ablation.
AB  - A study has been carried out of the RF field strength around a total of 17
      patients undergoing radio-frequency endometrial ablation in three hospital
      centres. The mean equivalent power density at the position of the surgeon
      exceeded 10 W m-2, which is the derived investigation level for exposure to
      electromagnetic fields. This value is derived from a basic restriction in the
      average specific absorption rate in the body to 0.4 W kg-1. This limit applies to
      general population as well as occupational exposure and is well below that which
      has been shown to be hazardous to health. Also, the working conditions did not
      place physical stress on the surgeon. The maximum value of the specific energy
      absorption rate in the head or trunk should not exceed 10 W kg-1. Measured values
      on the field strength suggest that this organ dose limit was not exceeded. It is
      concluded that staff exposure to stray RF radiation during radio-frequency
      endometrial ablation is not considered to be hazardous to health.

PMID- 8877755
TI  - Metal implant localizers: frontiers and diagnostic feasibility.
AB  - The paper describes and analyses a method for locating metal implants based on
      the interaction of a conductive object with a weak alternating magnetic field.
      Theoretical values for the boundary of detectability and the boundary of
      localability are introduced to show some technical characteristics, the
      diagnostic feasibility and limitations of the method. Clinical experiences are
      described in order to compare the theoretical expectations with practical
      results. Several advantages of the proposed diagnostic method in terms of
      inexpensive instrumentation, ease of operation and sensitivity are discussed.

PMID- 8877756
TI  - Detection by PCR of human papillomavirus genotypes in cervical lesions of
      Senegalese women.
AB  - In order to analyse human papillomavirus (HPV) infection in the Senegalese
      population, HPV DNA was sought in 65 women with evidence of cervical cytological
      abnormality and in 72 pregnant women. Ninety-four percent of the patients were
      positive for HPV DNA as compared to 24% of pregnant women. HPV 16 was detected in
      cervical smears in 42% of cases, HPV 18 in 39%, HPV 6 in 26%, HPV 11 in 15%, HPV
      45 in 10%, HPV 52 in 3%, and HPV 31, HPV 33 and HPV 68 in 1.5%. HPV 16 and HPV 18
      were detected in 16% and 7% respectively of pregnant women. HPV DNA of unknown
      type was detected in 6% of cases, and multiple HPV infections were observed in
      28% of cases. Low risk genital HPVs (6/11) were detected in smaller proportions
      (17%) among high grade squamous intraepithelial lesions (SILs) than the low grade
      SILs (43%). High risk HPVs (16/18) were detected in high proportions both in low
      and high grade SIL lesions, though the highest frequency (70%) was observed among
      patients with high grade lesions. In conclusion, the results confirm that HPV
      infections are frequent in Senegal and that HPV 18 and 45 are detected in a high
      proportion of patients in Africa.

PMID- 8877757
TI  - Enhancement of varicella-zoster virus infection in cell lines expressing ORF4- or
      ORF62-encoded proteins.
AB  - Varicella-Zoster virus (VZV) open reading frames 4 (ORF4) and 62 (ORF62) encode
      putative immediate early proteins (ORF4p and ORF62p, respectively) which are
      strong transactivators of other VZV genes and are involved in the very early
      stages of viral infection. ORF4p and ORF62p transactivate immediate-early and
      early gene promoters but have little or no effect on late gene promoters. To
      investigate the effect of ORF4p or ORF62p overexpression on the viral replication
      cycle, we constructed Vero cell lines expressing those genes under the control of
      the human cytomegalovirus major immediate-early promoter. VZV OKA infection of
      these stably transformed cell lines was followed-up using VZV glycoprotein E (gE)
      antigen quantification and virus titration. Upon serial passaging of infection in
      these cell lines expressing functionally active ORF4p or ORF62p, a 5- to 10-fold
      increase in viral gE antigen production was observed. Viral titers also
      demonstrated a 2- to 5-fold increase in viral production in these transformed
      cell lines. These results emphasize the role that both ORF4p and ORF62p play in
      enhancing the VZV replicative cycle.

PMID- 8877758
TI  - HLA DRB1 and DQB1 alleles and haplotypes influencing the progression of hepatitis
      C.
AB  - Some HLA class II alleles and haplotypes were examined by restriction fragment
      length polymorphism of corresponding DNA fragments amplified by the polymerase
      chain reaction in 117 patients with chronic hepatitis C in Japan. The prevalence
      rates were compared between patients and 1216 controls and in 67 patients with
      liver cirrhosis, of whom 20 had hepatocellular carcinoma and 50 patients with
      chronic hepatitis who did not have cirrhosis or hepatocellular carcinoma.
      Notably, DRB1*0405 (49% [95% confidence range 38-60%] vs. 26% [16-40%]; P < 0.05,
      relative risk [rr] = 2.8) and DQB1*0401 (43% [33-54%] vs. 22% [13-34%]; P < 0.05,
      rr = 2.1) were detected more frequently in patients with cirrhosis than in those
      without cirrhosis. By contrast, DRB1*0901 (11% [6-19%] vs. 28% [18-40%]; P <
      0.05; rr = 0.3) and DQB1*0303 (11% [6-19%] vs. 36% [25-49%]; P < 0.01; rr = 0.2)
      were detected less frequently in patients with cirrhosis than those without
      cirrhosis. Accordingly, the DRB1*0405-DQB1*0401 haplotype was more common (43%
      [33-54%] vs. 22% [13-34%]; P < 0.05; rr = 2.7), while the DRB1*0901-DQB1*0303
      haplotype was less common (9% [4-17%] vs. 28% [18-40%]; P < 0.05; rr = 0.3) in
      patients with cirrhosis than in those without cirrhosis. These results suggest
      that there would be HLA class II alleles and haplotypes which may be associated
      with an accelerated or slower progression of chronic hepatitis C towards
      cirrhosis and eventually to hepatocellular carcinoma.

PMID- 8877759
TI  - Evaluation of a new general primer pair for rapid detection and differentiation
      of HSV-1, HSV-2, and VZV by polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) enables rapid and sensitive detection of VZV
      and HSV DNA and its efficiency depends mainly on the choice of the primers.
      Primers should hybridize to conserved DNA sequences within the viral genomes in
      order to avoid unreliable amplification due to DNA sequence variation between
      different strains. The aim of the study was to design and to evaluate a general
      primer pair which permits fast and reliable detection of HSV and VZV. The genes
      UL 15 of HSV and UL 42 of VZV share the highest degree of homology within the two
      genomes. We designed a primer pair (GPHV-RU) which hybridizes to these genes. The
      genetic variability of amplified sequences from clinical specimens was analyzed
      by restriction enzyme cleavage analysis and by temperature gradient SSCP analysis
      (TG-SSCP). PCR with GPHV-RU amplified viral sequences from all analyzed specimens
      (25 x VZV, 10 x HSV-1, 5 x HSV-2) obtained from patients with clinical evidence
      of HSV or VZV infection. Restriction enzyme cleavage analysis with Hpa II further
      permitted reliable distinction between VZV, HSV-1, and HSV-2. Analysis of the
      heterogeneity of the amplified sequences by restriction enzyme cleavage and by TG
      SSCP demonstrated no variability between the analyzed clinical specimens of VZ
      and of HSV-2 and only one differing TG-SSCP-pattern within the HSV-1 isolates.
      The results suggest that detection of HSV and VZV using the new primer pair GPHV
      RU should give reliable results as the amplified sequences show little genetic
      variability within clinical isolates of HSV-1/2 and VZV.

PMID- 8877760
TI  - Coinfection of individual leukocytes with human cytomegalovirus and human
      immunodeficiency virus is a rare event in vivo.
AB  - Infection with the human cytomegalovirus (HCMV) accelerates disease progression
      in human immunodeficiency virus 1 (HIV-1)-infected individuals. This has been
      attributed to the transaction of HIV-1 gene expression by HCMV gene products. For
      transactivation to be effective in vivo both viruses must be present in the same
      cell. We therefore examined blood samples from 13 HIV-1-infected patients with
      HCMV viremia for coinfection of individual leukocytes. In four of the patients
      lymph nodes were also examined. Multiple samples contained defined numbers
      (between 10 and 1000) of CD4+ lymphocytes or CD14+ monocytes were sorted by a
      FACS-based automated cell deposition unit. Samples were then analysed by a
      multiplex nested polymerase chain reaction, which can detect simultaneously HCMV
      and HIV DNA. The percentage of infected cells was calculated for each virus using
      the Poisson distribution. Between 0.43% and 6.2% of the CD4+ lymphocytes were
      infected with HIV and less than 0.15% with HCMV. The level of infection in CD14+
      monocytes was always < or = 0.11% for HIV and ranged between < 0.05% and 0.58%
      for HCMV. Only seven of 1030 sorted samples from blood were positive for both
      viruses. In lymphnodes, none of the 144 samples tested were double-positive. This
      clearly shows that coinfection of individual human leukocytes with HIV and HCMV
      is a very rare event in vivo. Therefore, direct transactivation of HIV by HCMV in
      coinfected cells obtained from blood and lymphnodes may not explain the effect of
      HCMV on the prognosis of HIV-infected individuals.

PMID- 8877761
TI  - Detection of human herpes virus 6 in AIDS-associated retinitis by means of in
      situ hybridization, polymerase chain reaction and immunohistochemistry.
AB  - The ubiquitous nature of HHV-6 and its genomic relationship with cytomegalovirus
      led us to evaluate an etiological link between HHV-6 and AIDS-associated
      retinitis in a prospective study. HHV-6 infection was studied in patients with
      AIDS-associated retinitis and in two control populations. Eye pairs were obtained
      at necropsy from nine patients with AIDS-associated retinitis, four human
      immunodeficiency virus (HIV)-sero-positive patients with normal fundus
      examination and three HIV-seronegative patients. HHV-6 infection was detected by
      polymerase chain reaction (PCR), in situ hybridization and immunohistochemistry.
      Human cytomegalovirus (CMV) and HIV-1 infections were detected in parallel by the
      same methods. HHV-6 infection was detected in three cases of AIDS-associated
      retinitis. In two of these patients, HHV-6 infection was detected both by
      immunohistochemistry and PCR while in the third case it was detected by in situ
      hybridization and PCR. In the three patients, fundus examination showed bilateral
      retinitis in two of them and unilateral retinitis in one of them. HHV-6 infection
      was not detected in the retina of the two control groups. CMV was also detected
      in the three cases positive for HHV-6 by all three methods. HIV DNA was detected
      by PCR in two of three cases and was confirmed in one of these cases by in situ
      hybridization. These results confirm that HHV-6 infects the retina but suggests
      that HHV-6 does not have an exclusive causative role in AIDS-associated
      retinitis, since CMV coinfection of the retina was detected in all three of the
      patients positive for HHV-6.

PMID- 8877763
TI  - Reverse transcriptase genotype and antiretroviral susceptibility of human
      immunodeficiency virus isolates from patients with advanced disease treated with
      didanosine: correlation with virologic response and survival.
AB  - To identify correlates of virologic response and survival, the reverse
      transcriptase (RT) genotype and in vitro antiviral susceptibility of human
      immunodeficiency virus (HIV) isolates from 20 patients treated with didanosine
      were studied. Patients had advanced HIV disease and were intolerant to or had
      failed zidovudine. Neither RT genotype nor antiviral susceptibility testing, as
      determined by a peripheral blood mononuclear cell-based assay, correlated with a
      virologic response to didanosine, as determined previously by quantitative serum
      culture. Only one (8%) of 12 isolates obtained after 6-12 months of treatment
      showed mutation at codon 74 conferring didanosine resistance. Reversions were
      seen in three of five patients with pre-treatment zidovudine resistance mutations
      at codons 70, but in none of eight with mutations at codon 215. Pretreatment
      isolates encoding mutations at RT codon 215 or encoding codon 123 asp were
      associated with both significantly greater CD4 lymphocyte depletion and shorter
      survival. In this cohort of patients with advanced HIV disease, neither rapid
      emergence of didanosine resistance nor rapid reversion of zidovudine resistance
      was observed. To better understand the relationship between virologic response
      and in vitro susceptibility to didanosine, more precise tools may be needed.

PMID- 8877762
TI  - Nosocomial transmission of hepatitis C virus in haemodialysis patients.
AB  - A systematic virological follow-up of 114 haemodialysis patients treated in the
      same unit showed that 37, including 17 PCR positive patients, were seropositive
      for hepatitis C virus (HCV). Type 1b HCV was detected in 10 patients and was much
      more frequent in this population than in the whole population of patients treated
      in the hepatogastroenterology departments in southeastern France. The E1/E2
      genomic region of seven type 1b HCV strains was sequenced. In four patients, a
      similar strain was detected in both the E1 variable region and the E2
      hypervariable region (HVR1). In addition, two of these four patients were
      seronegative and PCR negative at the beginning of the study and had not been
      transfused or transplanted during this period. A phylogenetic tree was drawn
      which confirmed that these strains were very similar and showed that HCV was
      transmitted via the nosocomial pathway in this haemodialysis unit.

PMID- 8877764
TI  - Lymphocyte responses to human cytomegalovirus in different groups of patients in
      Britain and in adults from west Africa and the Middle East.
AB  - Antibody prevalence and lymphocyte proliferation responses to cytomegalovirus
      (CMV) and herpes simplex virus (HSV) were compared in several different groups of
      patients: genitourinary medical (GUM) patients, hemophiliacs, men with clinical
      acquired immunodeficiency syndrome (AIDS) and cases of primary CMV mononucleosis,
      and also in adults in the general population (control subjects) comprising
      separate groups native to Britain, West Africa, and the Middle East. Among the
      British control subjects who were positive for CMV IgG, all were also positive
      against CMV antigen by the lymphocyte transformation test (LTT). However, among
      those who were CMV IgG-positive in the various groups of patients, 20-86.9% gave
      positive responses to CMV antigen by the LTT; moreover, 75.7% and 55.5% of the
      CMV IgG-positive healthy control subjects from West Africa and the Middle East,
      respectively, gave positive LTT responses to CMV antigen. When the same groups of
      patients were tested for responsiveness to HSV antigen by the LTT, there was good
      agreement between a positive result by this test and by serology in all except
      those with primary CMV mononucleosis (42.8%). Overall, lymphocyte responses to
      CMV were significantly impaired in healthy, CMV antibody-positive subjects from
      West Africa and the Middle East compared to similar subjects from Britain.

PMID- 8877765
TI  - Analytic sensitivities of hybrid-capture, consensus and type-specific polymerase
      chain reactions for the detection of human papillomavirus type 16 DNA.
AB  - Human papillomavirus type 16 (HPV-16) DNA is detected commonly in cervical
      carcinomas; in this study, we have determined the analytical sensitivities of
      Hybrid Capture, HPV-consensus PCR, and three HPV-16-specific polymerase chain
      reactions (PCRs) for the detection of HPV-16 DNA. Samples investigated included a
      cervical cancer cell line, cervical scrapes from 20 patients attending colposcopy
      clinics, and buccal swabs from eight immunosuppressed children. HPV-16 E7 and E5
      nested PCRs [Cavuslu et al. (1996): Journal of Virological Methods, in press]
      produced positive signals from samples containing fewer than ten HPV-16 genomes
      per reaction. HPV-consensus PCR [Manos et al. (1989): Cancer Cells 7:209-214] and
      HPV-16 PCR using primers of van den Brule et al. [(1990): Journal of Clinical
      Microbiology 25:2739-2743] were of intermediate sensitivity (i.e., produced
      positive signals from samples containing 250 and 2,500 HPV-16 genoms/reaction,
      respectively) and Hybrid Capture could detect just 50,000 HPV-16
      genomes/reaction. Highest rates of positivity for cervical samples were detected
      with HPV-16 E7 or E5-nested PCRs [50% (10 of 20 samples) and 60% (12 of 20
      samples) positive, respectively], intermediate rates with HPV-consensus PCR and
      PCRs using the primers of van den Brule et al. [both 35% (7 of 20 samples)], and
      lowest rates of positivity [25% (5 of 20 samples)] with Hybrid Capture. None of
      eight buccal swab samples from immunosuppressed children were positive by Hybrid
      Capture, yet three (37.5%) were positive by HPV-16 E5-nested PCR. These data
      indicate that HPV-16 type-specific PCRs should be used for the investigation of
      specimens that may contain low amounts of HPV-16 DNA.

PMID- 8877766
TI  - Interferon vs. adenine arabinoside 5'-monophosphate in patients with anti-HBe
      positive chronic hepatitis.
AB  - Anti-HBe-positive patients with precore mutants may have severe, progressive
      liver disease. Therapy with interferon has been effective, but relapses are
      frequent. To evaluate and compare two antiviral treatments, lymphoblastoid
      interferon (ly-IFN) and adenine arabinoside 5'-monophosphate (ARA-AMP), 20
      patients with anti-HBe-positive chronic hepatitis (5 cirrhosis and 15 CAH) and
      viral replication (HBcAg in the liver and HBV DNA in serum) were treated.
      Patients were randomized into two groups: 11 patients received ARA-AMP, 5
      mg/kg/day during 7 weeks, and 9 received human ly-IFN, 5,000,000 units, three
      times per week, during 4 months. Baseline clinical, biochemical and histological
      features were not significantly different between the two groups. At the end of
      therapy, 8 (89%) patients in the interferon group and 5 (45%) in the ARA-AMP
      group showed normal ALT levels and no HBV DNA in serum by a liquid hybridization
      assay (P < 0.05). At 1 year of follow-up, a persistent response was observed in
      33% of ly-IFN patients and in 27% of ARA-AMP patients, a transient response in
      56% and 18%, and nonresponse in 11% and 55%, respectively. HBV DNA remained
      detectable by polymerase chain reaction (PCR) in 19 of the 20 patients. Among the
      responders, an improvement in histological lesion and the disappearance of
      intrahepatic HBcAg were observed; in the nonresponders, histological lesion
      remained stable or worsened. In conclusion, the efficacy of interferon and ARA
      AMP was similar in treating anti-HBe-positive chronic hepatitis. Although
      interferon treatment led to initial improvement in a larger number of patients,
      there was a much higher rate of relapses with this drug.

PMID- 8877767
TI  - Comparison of the association with eczema herpeticum in the two predominant
      genotypes of herpes simplex virus type 1.
AB  - Eczema herpeticum, sometimes called Kaposi's varicelliform eruption, is usually
      caused by a disseminated herpes simplex virus infection in a patient whose
      underlying skin disease in atopic dermatitis. Herpes simplex virus type 1 (HSV
      1), a widespread infectious agent in human populations, is the etiologic agent of
      eczema herpeticum. Analyses of restriction fragment length polymorphism (RFLP) of
      HSV-1 strains isolated in Japan, using restriction endonucleases, revealed the
      presence of two predominant genotypes of F1 and F35. The number of HSV-1 strains
      of F1 genotype was over twice that of the F35 genotype, and the nucleotide change
      between F1 and F35 was estimated to be 1.5%. The question of whether the genomic
      difference between two predominant genotypes could influence clinical
      manifestations remained to be addressed. On the basis of RFLP, we determined
      genotypes of HSV-1 strains isolated from the patients in Japan, including those
      with eczema herpeticum. Two of four HSV-1 strains of F35 genotype were from
      patients with eczema herpeticum, whereas none of 12 HSV-1 strains of F1 genotype
      was from those with eczema herpeticum. Thus, the F35 genotype seemed to be
      associated more frequently with eczema herpeticum than the F1 genotype.

PMID- 8877768
TI  - Immune responses to inactivated vaccine in people naturally infected with
      hantaviruses.
AB  - An inactivated Hantaan virus vaccine for hemorrhagic fever with renal syndrome
      (HFRS) was given by injection to 15 people who were naturally infected with
      either Hantaan or Seoul viruses. Immunofluorescent antibody (IFA), reversed
      passive hemagglutination inhibition (RPHI), hemagglutination inhibition (HI), and
      neutralization antibody (NA) assays were used to measure the antibody titers of
      the vaccinated people before and after three doses of vaccine. The results
      indicated that IFA and RPHI antibody titers were boosted significantly (P < 0.05)
      after the vaccination. Either Hantaan or Seoul virus could induce two-way cross
      reactive neutralization antibody responses in humans. After HTNV vaccine
      immunization, the NA titers of people with natural infection increased
      significantly (P < 0.05) to both Hantaan and Seoul viruses, while the relative
      dominance between these two type responses was still similar to that of natural
      infection. It is worthwhile to studying the procedure further to inoculate two
      different virus vaccines for improving the cross-protective effect.

PMID- 8877769
TI  - Sarcoplasmic reticulum genes are upregulated in mild cardiac hypertrophy but
      downregulated in severe cardiac hypertrophy induced by pressure overload.
AB  - Changes in contractile and relaxation properties of heart muscle in the cardiac
      hypertrophy induced by pressure overload have been attributed to alterations in
      intracellular Ca2+ transport as well as the phenotypic and quantitative changes
      in contractile protein. However, contradictory data have been reported regarding
      Ca2+ uptake, release and storage by the sarcoplasmic reticulum (SR). The purpose
      of this study was to evaluate the changes in SR Ca(2+)-ATPase, ryanodine
      receptor, calsequestrin and alpha-actin gene expression, and the changes in Ca2+
      uptake capacity in various degrees of hypertrophied hearts due to pressure
      overload. Cardiac hypertrophy was produced in rats by placing a constricting clip
      (0.80 mm) around the suprarenal abdominal aorta for 8 days. The mRNA levels and
      Ca2+ uptake capacity were then measured as a function of the severity of cardiac
      hypertrophy. Ca(2+)-ATPase and ryanodine receptor mRNA levels were increased in
      mildly hypertrophied hearts but were diminished in severely hypertrophied hearts,
      showing a bimodal response to pressure overload, Ca2+ uptake capacity showed
      similar changes along with a positive correlation with Ca(2+)-ATPase mRNA level
      (r = 0.67, P < 0.001). In contrast, the level of calsequestrin mRNA expression
      was unaltered and that of alpha-actin was markedly increased over a range of
      severity of cardiac hypertrophy. These findings suggest that the expression of
      sarcoplasmic reticulum genes for Ca2+ uptake and release is up- or downregulated
      dependent on the degree of pressure overload. The gene for the SR Ca2+ storage
      protein, calsequestrin, might be under different control from these genes in
      pressure overload. Our findings suggest that the decrease in ratio of mRNAs
      encoding Ca2+ uptake and release proteins to those encoding contractile proteins
      could significantly contribute to the slowed contractile and relaxation
      properties seen in pressure-overloaded hearts.

PMID- 8877770
TI  - Cellular and extracellular remodeling with the development and recovery from
      tachycardia-induced cardiomyopathy: changes in fibrillar collagen, myocyte
      adhesion capacity and proteoglycans.
AB  - The myocardial extracellular matrix (ECM) is composed of three important
      constituents: (1) fibrillar collagen, (2) a basement membrane, and (3)
      proteoglycans. Structural or compositional changes in these ECM components may
      affect left ventricular (LV) function as well as influence overall LV geometry.
      Accordingly, this study examined the relationship between changes in these ECM
      components to changes in LV function and geometry which develop with the
      progression and regression from supraventricular tachycardia-induced
      cardiomyopathy (SVT). LV function and specific components of the ECM were studied
      in pigs with SVT cardiomyopathy (SVT:atrially paced 240 bpm, 3 weeks; n = 7), or
      after a 4-week recovery from SVT cardiomyopathy (post-SVT; n = 6), and in
      controls (n = 7). LV fractional shortening fell by 60% and end-diastolic
      dimension increased by 47% with SVT compared to controls. While LV fractional
      shortening normalized with post-SVT, end-diastolic dimension remained 40% higher
      than controls. Collagen concentration fell by 22% and salt extractable collagen,
      which reflects collagen cross-linking, increased by 41% with SVT compared to
      controls. Collagen concentration increased by 20%, collagen extraction
      normalized, and levels of collagen type III mRNA increased by 42% with post-SVT.
      Isolated myocyte adhesion capacity to basement membrane substrates laminin,
      fibronectin, and collagen type IV were examined. SVT resulted in over a 50%
      reduction in myocyte adhesion for all of the basement membrane components
      compared to controls. A normalization in isolated myocyte adhesion capacity was
      observed in post-SVT. The relative content and distribution of the ECM
      proteoglycan chondroitin sulfate was examined using immunohistochemistry. With
      SVT, the density of this proteoglycan increased around individual myocytes. With
      post-SVT, the relative distribution of chondroitin sulfate returned to control
      levels. Thus, SVT cardiomyopathy was associated with reduced collagen
      concentration and cross-linking, diminished myocyte basement membrane adhesion
      capacity, and increased proteoglycans. Recovery from SVT cardiomyopathy resulted
      in increased collagen concentration, and a normalization of myocyte adhesion
      capacity and proteoglycan distribution. These results suggest that changes within
      the ECM are a dynamic process and accompany the LV systolic and diastolic
      function as well as ventricular and myocyte remodeling during the progression and
      regression from cardiomyopathic disease.

PMID- 8877771
TI  - A mutation in HERG associated with notched T waves in long QT syndrome.
AB  - Long QT syndrome (LQT) is a genetically heterogeneous inherited disorder that
      causes sudden death from cardiac arrhythmia. Four loci have been mapped to
      chromosomes 3, 4, 7 and 11 and three specific mutated genes for LQT syndrome have
      been identified. LQT2 results from mutations in the human ether-a-gogo-related
      gene, HERG, a cardiac potassium channel, whose protein product likely underlies
      Ikd the rapidly activating delayed rectifier current. By SSCP analysis and direct
      sequencing, we determined a new missense mutation in the HERG coding sequence, a
      G to A transition at position 1681 resulting in the substitution of threonine for
      a highly conserved alanine at codon 561. This mutation, Ala561Thr, in the coding
      sequence of the fifth membrane-spanning domain (S5) of the HERG protein seems to
      convey a risk of cardiac events in affected family members. In addition to a
      prolonged T wave of low amplitude on the surface ECG, a distinctive biphasic T
      wave pattern was found in the left precordial leads of all affected subjects with
      the Ala561Thr mutation regardless of age, gender and beta blocking therapy.

PMID- 8877772
TI  - Cultured neonatal rat heart cells can be preconditioned by ischemia, but not by
      heat shock. The role of stress proteins.
AB  - In this study we attempted to induce tolerance to simulated ischemia in beating
      cultured neonatal rat cardiomyocytes by subjecting them either to elevated
      temperatures or to a short period of simulated ischemia. This was done to
      investigate whether development of tolerance can be observed at the isolated,
      contracting myocyte level, as has been already described for intact organs: and
      whether the effect of preconditioning already become apparent during ischemia
      alone, as opposed to ischemia-reperfusion protocols. We find that no
      preconditioning can be achieved by a preceeding heat treatment. On the other
      hand, subjecting the cells to a non-lethal period of ischemia significantly
      reduces myocyte death during a second more severe ischemic insult. Both
      pretreatments induce elevated levels of the major fully inducible species of the
      hsp70 family, hsp68, making it unlikely that the presence of this protein is the
      sole determinant during preconditioning. The mRNA levels of several heat shock
      proteins (hsps) are increased by both treatments. However, these mRNAs are
      induced with different patterns, the most notable difference being the induction
      of hsp60 mRNA by ischemia, and the absence of this induction by heat shock. We
      further find that, contrary to some earlier reports, simulated ischemia activates
      the heat shock transcription factor (HSF) rapidly, as is the case for heat shock.

PMID- 8877773
TI  - Endotoxin and cytokines induce direct cardiodepressive effects in mammalian
      cardiomyocytes via induction of nitric oxide synthase.
AB  - In patients with septic shock or inflammatory cardiac diseases like myocarditis
      myocardial contractility is depressed. These patients have elevated circulating
      levels of bacterial endotoxins (lipopolysaccharides, LPS) and pro-inflammatory
      cytokines like interleukin-1 beta (IL-alpha 1 beta) or tumor necrosis factor
      alpha (TNF-alpha). It is not clear, whether LPS and/or cytokines have direct
      inotropic effects on cardiomyocytes and whether these effects are mediated via
      the L-arginine-nitric oxide synthase (NOS) pathway as demonstrated in vascular
      smooth muscle cells. Therefore, we examined the direct effects of LPS. IL-1 beta
      and TNF-alpha on contractility and cGMP content in isolated guinea-pig
      ventricular cardiomyocytes. Furthermore, the influence of the NOS inhibitor NG
      nitro-L-arginine (L-NNA) and dexamethasone on these effects was studied as well
      as inducible NOS (iNOS) protein expression. LPS (1000 ng/ml), IL-1 beta (25
      ng/ml) and TNF-alpha (100 ng/ml) decreased contractility by 48%, 55% and 65% and
      augmented cGMP content by 135%, 88% or 70% after long-term treatment (18 h) in
      cardiomyocytes, without altering contractility or cGMP content after short-term
      treatment (30 min). These effects were blocked by L-NNA (100 microM) and
      dexamethasone (3 microM). Furthermore iNOS protein was expressed in LPS- and
      cytokine-treated cardiomyocytes. These findings demonstrate that LPS. IL-1 beta
      and TNF-alpha have direct negative inotropic effects on cardiomyocytes, which are
      accompanied by an increase in cGMP content. These effects are mediated via de
      novo synthesis of a myocardial iNOS. The direct negative inotropic effects of
      endotoxins and cytokines on cardiomyocytes may in part contribute to the
      contractile dysfunction observed in patients with septic shock or inflammatory
      cardiac diseases.

PMID- 8877774
TI  - Na-dependent regulation of intracellular free magnesium concentration in isolated
      rat ventricular myocytes.
AB  - Changes in ionized intracellular free magnesium concentration [Mg2+]i were
      measured in isolated, superfused rat ventricular myocytes using mag-fura-2. Cells
      were superfused with media containing high or low Mg concentrations ([Mg]o), with
      and without Na (Nao) and/or Ca (Cao). Increasing [Mg]o from 1 to 5 mmol/l in Ca
      free solutions had no significant effect on [Mg2+]i when [Na]o was normal.
      However, [Mg2+]i rose steadily when Nao was completely replaced by either
      tetramethylammonium (TMA) or K. This [Mg2+]i rise was inhibited by imipramine (10
      mumol/l) but not by verapamil (25 mumol/l). [Mg2+]i returned rapidly from a high
      to its initial level on superfusing cells with basic medium containing normal Ca,
      Na and Mg. [Mg2+]i recovery required Nao and was inhibited by imipramine (10
      mumol/l). When Mgo was removed from Ca-free superfusates, the [Mg2+]i decreased
      whether or not Nao was present. However, [Mg2+]i decreased most when Nao was
      replaced by K. Neither imipramine nor verapamil affected the magnitude of this
      fall, but verapamil slowed it. [Mg2+]i rapidly increased to normal when depleted
      cells were superfused with basic medium with or without Cao. Both imipramine and
      verapamil slowed this recovery. Superfusion of cells with Ca-free media
      containing strophanthidin (20 mumol/l) caused [Mg2+]i to rise, but only if the
      medium contained Mg (1 mmol/l). The data suggest that Mg can enter cardiac
      myocytes through routes which close when physiological [Mg2+]i is attained. One
      pathway for Mg flux is by a Na-dependent, imipramine-sensitive mechanism which is
      probably a Na-Mg antiport.

PMID- 8877775
TI  - Expression of phenylethanolamine n-methyltransferase in the embryonic rat heart.
AB  - Phenylethanolamine N-methyltransferase (PNMT), the final enzyme in the pathway
      for epinephrine biosynthesis, serves as a marker for tissues and cells producing
      epinephrine. The present study examines the developmental expression of PNMT in
      the rat embryo. A transient burst in PNMT mRNA expression begins on embryonic day
      9.5 (E9.5), peaks between E10.0 and E11.0, and declines to barely detectable
      levels by E13.0. Regional localization of PNMT mRNA and enzyme activity
      demonstrates that PNMT is concentrated in the heart. PNMT has not previously been
      reported to be expressed at these early stages of development, and its presence
      in the developing heart suggests that this embryonic tissue may produce
      epinephrine. Because this catecholamine is known to increase cardiac output and
      promote the growth of cardiomyocytes, local production of epinephrine by the
      heart could play an important role in the development of cardiac structure and
      function.

PMID- 8877776
TI  - Beneficial effects of angiotensin I converting enzyme inhibitor on post-ischemic
      contractile function of perfused rat heart.
AB  - The present study was undertaken to determine whether trandolaprilat, an active
      form of angiotensin I converting enzyme (ACE) inhibitor, may improve
      ischemia/reperfusion-induced contractile dysfunction and metabolic derangement of
      isolated rat hearts. Ischemia (25 min) and subsequent 60-min reperfusion resulted
      in a small recovery of post-ischemic left ventricular developed pressure (LVDP),
      a sustained increase in left ventricular end-diastolic pressure, an increase in
      the release of creatine kinase and ATP metabolites from the perfused heart, and
      changes in myocardial sodium, potassium, calcium and magnesium contents.
      Treatment with 10-100 microM of trandolaprilat for the last 10 min of pre
      ischemia recovered approximately 50-90% of pre-ischemic LVDP during reperfusion,
      whereas that with 30-100 microM of enalaprilat restored approximately 55-65% of
      the pre-ischemic LVDP. Treatment with either trandolaprilat or enalaprilat at
      these concentrations attenuated the release of creatine kinase and ATP
      metabolites into the perfusate during reperfusion. Treatment with 30 microM
      trandolaprilat suppressed ischemia/reperfusion-induced changes in myocardial ion
      content. Treatment with bradykinin during the last 10 min of pre-ischemia also
      resulted in a post-ischemic contractile recovery with a degree similar to that of
      the trandolaprilat-treated hearts. E4177, an AT1-antagonist, showed no effect on
      ischemia/reperfusion-induced changes in cardiac parameters. The enhancement of
      post-ischemic contractile recovery by the ACE inhibitor was abolished by
      treatment with either Hoechst 140, a bradykinin (BK2) antagonist, or diclofenac,
      a cyclooxygenase inhibitor. These results suggest that trandolaprilat is capable
      of attenuating ischemia/reperfusion injury of isolated perfused hearts and
      altered BK metabolism is, at least in part, involved in this effect.

PMID- 8877777
TI  - Importance of the early alterations of energy metabolism in the induction and the
      disappearance of ischemic preconditioning in the isolated rat heart.
AB  - The kinetics of alterations in high energy phosphates were studied in isolated
      rat hearts during single and multiple ischemic preconditioning (IPC) using [31P]
      nuclear magnetic resonance (NMR) spectroscopy. Aortically perfused hearts were
      subjected to a 25 min sustained ischemia and a 30 min reperfusion. The IPC
      protocols used a basic pattern of 3 min ischemia plus 6 min reflow, increasing
      the reflow period from 6 to 12 min. Efficient IPC was associated during ischemia
      with a reduction in ATP degradation, in intracellular acidosis and a maintenance
      of a residual pool of PCr. Analysis of the IPC phase showed that each short
      ischemia was followed by a vasodilation (40-50%), accompanied by a clear PCr
      overshoot (115-125%) and a cytosolic Pi undershoot. Thus, the energy producing
      reactions were swung out of their initial equilibrium. The PCr overshoot remained
      up to the onset of the sustained ischemia in the efficient protocols, whereas it
      has practically vanished in the unefficient ones. In addition, the duration of
      such a positive imbalance appeared reinforced and prolonged by multiple IPC. It
      is suggested that an IPC cycle induced a time-dependent positive imbalance in the
      mitochondrial oxphosphorylative reactions. The benefit for the heart developed
      only when the prolonged ischemia was imposed under such conditions, modifying
      thereby the early dynamics of the energy metabolism processes during the initial
      phase of the sustained ischemia.

PMID- 8877778
TI  - Alterations in skeletal muscle gene expression in the rat with chronic congestive
      heart failure.
AB  - Congestive heart failure is often associated with skeletal muscle abnormalities
      that contribute to early fatigue and acidosis. Up to the present time, however,
      the mechanisms responsible for these changes are unclear. Myocardial infarctions
      were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10
      control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1
      +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)]
      underwent in vivo measurements of total body, and soleus total protein and myosin
      heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was
      also analysed for protein content, and MHC isoenzyme content by SDS-PAGE.
      Northern blotting also was used to determine levels of the mRNA's encoding type
      I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus
      muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5
      mg) and the degree of atrophy was significant when corrected for body mass (0.38
      +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant
      difference in plasma leucine flux (an index of whole-body protein synthesis),
      soleus muscle total and MHC synthesis was reduced in heart failure animals.
      Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the
      soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the
      MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding
      beta MHC were significantly depressed in the heart failure rats, where those
      encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha
      skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH)
      were also significantly depressed. This animal model of chronic heart failure is
      associated with quantitative and qualitative alterations in skeletal muscle gene
      expression that are similar to those reported in skeletal muscle of patients with
      chronic heart failure. The altered phenotype and impaired metabolic capacity may
      contribute to exercise intolerance in CHF.

PMID- 8877779
TI  - Sarcoplasmic reticulum calcium uptake in human myocardium subjected to ischemia
      and reperfusion during cardiac surgery.
AB  - We evaluated the effect of ischemia and reperfusion on sarcoplasmic reticulum Ca
      uptake in patients subjected to cardiac surgery. Our series included 16 patients
      (seven female, nine male, age 63 +/- 2 years): five were subjected to aortic
      valve replacement, five to aortic and mitral valve replacement, six to coronary
      artery bypass graft. In each case no clinical, electrocardiographic or
      echocardiographic evidence of perioperative infarction was observed. Biopsies
      were obtained from the right atrium of each patient before starting
      extracorporeal circulation, and after the recovery of spontaneous contractile
      activity, i.e. after cardioplegia-ischemia-reperfusion. The tissue was
      homogenized, and oxalate-supported Ca uptake, which represents sarcoplasmic
      reticulum Ca uptake, was measured in the unfractionated homogenate. The assay was
      performed under basal conditions and in the presence of 900 microM ryanodine, in
      order to block sarcoplasmic reticulum Ca release channels. Under basal conditions
      at pCa = 5.85 the rate of sarcoplasmic reticulum Ca uptake averaged 4.76 +/- 0.37
      nmol/min per mg of protein in the pre-ischemic samples, and decreased
      significantly in the post-ischemic samples (3.09 +/- 0.29 nmol/min per mg, P <
      0.01). A significant decrease of Ca uptake after ischemia and reperfusion was
      observed also in the presence of ryanodine (3.53 +/- 0.48 nmol/min per mg)
      compared to pre-ischemic values (5.98 +/- 0.56 nmol/min per mg, P < 0.01).
      Additional experiments showed no change in the Ca sensitivity of Ca uptake in the
      postischemic samples (Kca = 0.48 +/- 0.02 microM, no significant difference after
      ischemia and reperfusion). In conclusion, active sarcoplasmic reticulum Ca
      transport was impaired in human atrial myocardium after reversible ischemia and
      reperfusion.

PMID- 8877780
TI  - Adenovirus-mediated increase of exogenous and inhibition of endogenous fosB gene
      expression in cultured pulmonary arterial smooth muscle cells.
AB  - Modification of gene expression in pulmonary arterial smooth muscle cells
      (PASMCs) could be a valuable tool for investigating the role of specific gene
      products in normal and pathological PASMC growth, and a novel potential therapy
      for pulmonary vascular diseases. To examine the direct role of fosB protein in
      PASMC growth, adenovirus (Ad) vectors were used to transfer sense or antisense
      full-length fosB cDNAs to cultured PASMCs to modify fosB expression, and
      investigate the effects of this modification on PASMC growth. The full-length
      fosB cDNA under the control of the cytomegalovirus (CMV) early gene promoter was
      constructed into an E1 region-deleted, replication-deficient human type 5 Ad
      vector in either sense or antisense orientation. Forty-eight hours after
      infection with the sense construct (Ad.S. fosB) at 3 plaque-forming units per
      cell (pfu/cell). PASMCs expressed abundant fosB mRNA and fosB protein. FosB
      protein was detected by immunohistochemistry in approximately 95% of the infected
      cells. PASMCs infected with Ad.S.fosB at ratios of 0.1, 0.2, 0.5, 1.3, and 10
      pfu/cell showed a dose-dependent increase in fosB mRNA expression, with half
      maximal and maximal expression at 1 and 10 pfu/cell, respectively. The increase
      in fosB mRNA expression was detected as early as 8 h and persisted for 25 days
      after infection. Forty-eight hours after infection with the antisense construct
      (Ad.A.fosB) at 3 pfu/cell, very low levels of fosB mRNA were detected by Northern
      blotting, in which the double-stranded fosB cDNA was labeled and used as a
      hybridization probe. FosB protein was undetectable by Western blotting or
      immunocytochemical analyses in the Ad.A.fosB infected cells. Cytopathical effects
      were observed when PASMCs were infected with either Ad.S.fosB or Ad.A.fosB at
      ratios of 10 pfu/cell or higher. Infection of serum-deprived PASMCs with
      Ad.S.fosB or Ad.A.fosB alone at 3 pfu/cell did not affect cellular growth. These
      results show that adenoviral vectors containing sense or antisense fosB cDNA
      expression units can be used to effectively modify fosB gene expression. Although
      changes in fos-B gene expression did not affect cellular growth, this model
      system offers a very effective method for elucidating the biological roles of
      other gene products and studying the pathways of PASMC gene regulation and signal
      transduction.

PMID- 8877781
TI  - Effect of acidosis on contraction, intracellular pH and calcium in the rabbit
      mesenteric small artery.
AB  - The purpose of the present study was to determine the effect of various types of
      acidosis on vessel diameter, intracellular pH (pHi), and calcium concentration
      ([Ca2+]i) in a cannulated preparation of the mesenteric arteriole of the rabbit.
      The effect of acidosis on vessel contraction was also studied in the wire-mounted
      preparation. In the cannulated preparation, pre-contracted by noradrenaline,
      hypercapnia caused vasoconstriction and increases in [Ca2+]i. In the wire-mounted
      preparation pre-contracted by either noradrenaline or high KCl, hypercapnia
      caused a transient vasoconstriction. In contrast, in the cannulated preparation
      pre-contracted by high KCl, hypercapnia caused a transient vasorelaxation and
      decreases in [Ca2+]i. Intracellular acidosis, induced by a NH4Cl prepulse, caused
      vasoconstriction and increases in [Ca2+]i even in the cannulated preparation pre
      contracted by high KCl. The decrease in pHi during hypercapnia was similar to
      that observed after NH4Cl withdrawal. These data suggest that: (1) the effect of
      acidosis on vascular tone and [Ca2+]i is different depending upon the type of
      preparation and the mode of pre-activation, and (2) [Ca2+]i may, at least partly,
      regulate vascular contraction and relaxation during acidosis.

PMID- 8877782
TI  - AT1 receptor gene regulation in cardiac myocytes and fibroblasts.
AB  - The regulation of the AT1 receptor gene was studied in neonatal cardiomyocytes
      and fibroblasts in vitro. Incubation with angiotensin II (Ang II) resulted in a
      time-dependent and dose-dependent decrease in AT1 mRNA levels in both
      cardiomyocytes and fibroblasts. Coincubation with Ang II and the specific AT1
      antagonist losartan prevented the decrease in AT1 mRNA whereas the AT2 antagonist
      PD123319 was ineffective in preventing the decrease in AT1 mRNA. Because Ang II
      is known to decrease cAMP levels in cardiomyocytes, the role of cAMP in the
      regulation of the AT1 gene was examined. Treatment with the adenylyl cyclase
      stimulant forskolin or the cAMP stereoisomer Sp-cAMPS increased AT1 mRNA levels
      or prevented the Ang II mediated decrease in AT1 mRNA levels. The role of calcium
      in the regulation of the AT1 gene was determined by incubation with the calcium
      ionophores A23187 and ionomycin (0.0625-1 microM) which resulted in a profound,
      dose-dependent decrease in AT1 mRNA levels. Treatment with BAPTA, an
      intracellular chelator of calcium, prevented the Ang II-mediated decrease in AT1
      mRNA. Therefore Ang II is a potent negative regulator of the AT1 gene in
      cardiomyocytes and fibroblasts via the AT1 receptor. This Ang II mediated
      decrease in AT1 mRNA is mediated by two complementary mechanisms involving cAMP
      and intracellular calcium.

PMID- 8877783
TI  - Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during
      postnatal development.
AB  - The switch from myocyte hyperplasia to hypertrophy occurs during the early
      postnatal period. The exact temporal sequence when cardiac myocytes cease
      dividing and become terminally differentiated is not certain, although it is
      currently believed that the transition takes place gradually over a 1-2-week
      period. The present investigation has characterized the growth pattern of cardiac
      myocytes during the early postnatal period. Cardiac myocytes were enzymatically
      isolated from the hearts of 1, 2, 3, 4, 6, 8, 10, and 12-day-old rats for the
      measurements of binucleation, cell volume and myocyte number. Almost all myocytes
      were mononucleated and cell volume remained relatively constant during the first
      3 days of age. Increases in cell volume and binucleation of myocytes were first
      detected at day 4. Myocyte volume increased 2.5-fold from day 3 to day 12 (1416
      +/- 320 compared to 3533 +/- 339 microns 3). The percentage of binucleated
      myocytes began to increase at day 4 and proceeded at a high rate, reaching the
      adult level of approximately 90% at day 12. Myocyte number increased 68% during
      the first 3 days (from 13.6 +/- 3.5 x 10(6) at day 1 to 22.9 +/- 5.6 x 10(10) at
      day 3) and remained constant thereafter. To confirm that no further myocyte
      division exists after 4 days, bromodeoxyuridine (Brdu) was administered to 4-day
      old rats and the fate of DNA-synthesizing myocytes was examined 2 h and 2, 4, 6
      and 8 days after Brdu injection. About 12% of myocytes were labeled with Brdu at
      2 h and all were mononucleated at that time. Gradually, these Brdu-labeled
      myocytes became binucleated. However, the percentage of labeled myocytes in all
      groups was identical, indicating that DNA-synthesizing myocytes were becoming
      binucleated without further cell division after 4 days of age. Within 8 days
      after injection, approximately 82% of total labeled myocytes were binucleated,
      while the others remained mononucleated. Sarcomeric alpha-actinin was fully
      disassembled in dividing myocytes of 2-day-old rats, while typical alpha-actinin
      striations were present in dividing myocytes of 4-day-old rats. The results from
      this study suggest that a rapid switch from myocyte hyperplasia to hypertrophy
      occurs between postnatal day 3 and 4 in rat hearts.

PMID- 8877784
TI  - ATPase activity and force production in skinned rat cardiac muscle under
      isometric and dynamic conditions.
AB  - ATPase activity and force were determined in maximally activated skinned cardiac
      trabeculae from rat at 20 degrees C, 2.2 microns sarcomere length and pH 7.0.
      Measurements were performed during isometric contraction, and when square-wave
      shaped length changes with an amplitude of 0.5-5% of the resting length (Lo) and
      a repetition frequency of 2-167 Hz were imposed. Isometric ATPase activity
      amounted to 0.48 +/- 0.04 mM/s, and isometric force was 53 +/- 3 kN/m2. During
      length changes, an increase in ATP consumption was observed, reminiscent of the
      Fenn effect, to a maximal value of 1.7 times the isometric value, while the
      average force decreased. The frequency dependent increase in ATPase activity
      during length changes is compatible with a mono exponential recovery process,
      with a rate constant of 32 +/- 7/s. In a two-state scheme of crossbridge cycling,
      an apparent attachment rate of 28.6/s and an apparent detachment rate of 3.4/s
      were determined. To relate these observations with crossbridge kinetics during
      isotonic shortening, ramp-shaped length changes (2.5% Lo, 23 Hz) were imposed.
      ATPase activity and average force during ramp shortenings were similar to the
      values obtained during square-wave shaped length changes with the same amplitude
      and frequency. During lengthening ramps, the increase in ATPase activity and the
      decrease in average force were significantly less than during the square-wave
      protocol. These results indicate that the energetic effect of stretches is
      relatively small.

PMID- 8877785
TI  - Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial
      ischemia reperfusion injury.
AB  - To test the authors' hypothesis that cellular antioxidant enzymes constitute a
      cellular defense against acute stress, myocardial ischemia reperfusion injury in
      transgenic mice overexpressing the cellular glutathione peroxidase (GSHPx-1) was
      studied. Transgenic mice were generated using the entire mouse GSHPx-1 gene
      including approximately 2.0 kb 5'flanking sequence. A 400% increase of GSHPx
      activity was found in the hearts of transgenic mice compared with non-transgenic
      controls. Isolated perfused hearts were prepared from two groups of mice:
      transgenic overexpressed; non-transgenic controls. Hearts were perfused by
      Langendorff mode, and after 10 min of stabilization subjected to 30 min of
      ischemia followed by 20 min of reperfusion. In addition, a group of hearts were
      perfused for 50 min without subjecting them to ischemia and reperfusion to
      demonstrate the stability of heart preparation. Transgenic mouse hearts
      demonstrated significantly improved recovery of contractile force and the rate of
      contraction, compared to non-transgenic control mouse hearts. The infarct size
      was also lower in transgenic mouse hearts compared to those of non-transgenic
      controls. In concert, following ischemia, release of creatine kinase from the
      transgenic hearts was significantly lower than the control group. The results of
      this study indicate that increased GSHPx-1 expression renders the heart more
      resistant to myocardial ischemia reperfusion injury.

PMID- 8877786
TI  - Effects of increasing intracellular reactive iron level on cardiac function and
      oxidative injury in the isolated rat heart.
AB  - Elevation of cell iron content was produced by use of a lipophilic iron ligand, 8
      hydroxyquinoline (HQ), capable of transferring catalytically active iron into
      cells. The Fe(3+)-HQ complex labeled with 59Fe was avidly taken up by isolated
      perfused hearts contrary to the hydrophilic complex Fe(3+)-citrate. Hearts
      perfused in aerobic conditions with Krebs-Henseleit buffer were exposed for 15
      min to the iron complexes, Fe(3+)-HQ (5 microM/10 microM and 10 microM/20
      microM), or Fe(3+)-citrate (10 microM), and then perfused for 30 min with normal
      buffer. Exposure to the high dose of Fe(3+)-HQ (10 microM/20 microM) resulted in
      early and irreversible decreases in coronary flow and heart rate (-48% and -33%,
      respectively), initial increases followed by decreases in left ventricular
      systolic pressure and +dP/dt, and increase in left ventricular end-diastolic
      pressure (+80%). The low dose of Fe(3+)-HQ (5 microM/10 microM) mimicked with a
      lower magnitude the effects of the high dose, whereas Fe(3+)-citrate had no
      effects on cardiac parameters. Only hearts exposed to the high dose of Fe(3+)-HQ
      exhibited a significant increase (+60%) in thiobarbituric acid-reactive substance
      level, an index of lipid peroxidation. The production of hydroxyl radicals was
      investigated by measuring 2,3-dihydroxybenzoic acid level in the coronary
      effluent after addition of salicylic acid (1 mM) in the perfusate. An immediate
      and high increase (x6) was seen during heart exposure to Fe(3+)-HQ (10 microM/20
      microM) and to Fe(3+)-citrate (10 microM). Considering Fe(3+)-citrate had no
      effect on cardiac function and lipid peroxidation it was concluded that this
      hydroxyl radical formation occurring in the extracellular space was not
      implicated in Fe(3+)-HQ-induced cardiac dysfunction. These results demonstrate
      the deleterious effect of increasing intracellular reactive iron level in non
      ischemic hearts.

PMID- 8877787
TI  - Force-relaxant actions of dimethyl sulfoxide on guinea-pig and rabbit papillary
      muscles.
AB  - Recent voltage-clamp analysis of dimethyl sulfoxide (DMSO: 0.1-10% v/v) action on
      membrane currents in guinea-pig ventricular myocytes (strong inhibition of
      delayed-rectifier K+ current, inhibition of Na+ pump current, little effect on L
      type Ca2+ current) suggested that the solvent would have a strong positive
      inotropic effect on guinea-pig papillary muscles. In muscles driven at 1 Hz, the
      major effects of 30 min superfusion with hyperosmotic 10% DMSO were: (1) a 33%
      lengthening of the action potential duration; (2) a 23% depression of developed
      tension; and (3) a pronounced positive inotropy on washout of the solvent.
      Osmotic change in cell volume was a possible reason for these effects; however,
      hyperosmotic sucrose solution that shrunk myocyte volume by a DMSO-like 12%
      failed to elicit the DMSO response. It was postulated that DMSO has both
      stimulatory and inhibitory actions: during treatment the stimulatory component
      (Ca2+ accumulation due to action potential lengthening and Na+ pump inhibition)
      is masked by a concomitant inhibition of Ca(2+)-myofilament interaction; removal
      of the solvent reveals the Ca2+ overload. In support of this interpretation. (1)
      DMSO depressed developed tension by up to 85% when the stimulatory influence was
      attenuated by eliminating action potential lengthening (rabbit papillary
      muscles), relieving pump inhibition (elevated K+), or preloading Ca2+ (low-K+ or
      low-Na+ superfusate), and (2) DMSO relaxed Na(+)-free contractures, and nearly
      abolished caffeine-induced contractures, in quiescent guinea-pig muscles. These
      data suggest that DMSO has a reversible, powerful inhibitory action on the
      myofilament force-generating machinery.

PMID- 8877788
TI  - Localization of the angiotensin II receptor subtypes in the human atrium.
AB  - Angiotensin II has two major receptor subtypes, designated AT1 and AT2. Both have
      been detected in the heart of several species, but most of the known functions of
      angiotensin II seem to be mediated through the AT1 receptor. The major objective
      of this study was to specify the cell type on which the AT2 receptor is located
      in the atrium of human heart. Right atrial biopsies from patients with coronary
      artery disease were tested in membrane binding assays and found to contain high
      levels of angiotensin II receptor (820 +/- 175 fmol/mg), 82 +/- 2% of which was
      of the AT2 subtype. Cryostat sections of these biopsies were incubated with 125I
      [Sar1,Ile8] angiotensin II in the presence of selective concentrations of the
      cold ligands losartan and CGP 42112A to detect the subtypes using microscopic
      autoradiography. High local densities of the AT2 receptor were observed.
      Comparison of the labelling patterns thus obtained with adjacent sections stained
      for vimentin, collagen, neurofilaments or acetylcholinesterase revealed that the
      high densities of AT2 receptor were always associated with fibrous tissue.
      However, the AT1 receptor was in general evenly distributed over the tissue at
      low concentrations. Higher local concentrations of this receptor subtype were
      observed on nervous tissue. The present finding of high densities of the AT2
      receptor on fibroblasts at sites of fibrosis may have important clinical
      implications. Further studies to elucidate the function of this receptor subtype
      in the heart are therefore essential and the clinical consequences of the use of
      AT1 antagonists on post-infarction remodelling should be investigated.

PMID- 8877789
TI  - No attenuation of ischaemic preconditioning by the calcium antagonist
      nisoldipine.
AB  - In anaesthetized dogs, intracoronary infusion of calcium prior to a prolonged
      ischaemic period reduced infarct size, thereby mimicking the protective effects
      of ischaemic preconditioning and suggesting that an increase in the intracellular
      calcium concentration might be an important mechanism underlying this phenomenon.
      The aim was to determine whether pretreatment with the calcium antagonist
      nisoldipine attenuates the reduction in infarct size achieved by ischaemic
      preconditioning. In 10 enflurane-anaesthetized pigs serving as controls (group
      1), the inflow into the cannulated left anterior descending coronary artery was
      reduced (low-flow ischaemia) to achieve a 90% reduction in an anterior myocardial
      work index (sonomicrometry) for 90 min. In 11 pigs (group 2), a cycle of 10 min
      of low-flow ischaemia and 15 min of reperfusion (preconditioning) preceded the
      prolonged ischaemia. In groups 3 (n = 9) and 4 (n = 7), nisoldipine was
      administered by intravenous infusion (500 ng/kg/min) starting 40 min prior to and
      then throughout a protocol identical to that of groups 1 and 2, respectively.
      Subendocardial blood flow was measured with radiolabelled microspheres. Infarct
      size (% area at risk) was determined by triphenyltetrazolium staining in all pigs
      after 120 min of reperfusion. Subendocardial blood flow in the area at risk was
      similar in all four groups (group 1: 0.09 +/- 0.04 ml/min/g; group 2: 0.05 +/-
      0.03; group 3: 0.09 +/- 0.03; group 4: 0.07 +/- 0.03). Group 2 had reduced
      infarct size when compared with group 1 (2.6 +/- 3.0% v 12.4 +/- 8.7%, P =
      0.004), and there was a trend for a reduction in infarct size following
      nisoldipine treatment (group 3: 10.2 +/- 7.1%, group 4: 1.6 +/- 2.8%, P = 0.01).
      Thus administration of nisoldipine in pigs tended to decrease infarct size, and
      did not abolish the cardioprotection afforded by ischaemic preconditioning.

PMID- 8877790
TI  - Two cardiac natriuretic peptide genes (atrial natriuretic peptide and brain
      natriuretic peptide) are organized in tandem in the mouse and human genomes.
AB  - Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which act
      as cardiac hormones, are produced mainly by the atrium and ventricle,
      respectively, and are involved in body fluid homeostasis and blood pressure
      control. The ANP and BNP gene expressions are markedly augmented in ventricles of
      patients with a wide variety of cardiovascular diseases. It has been demonstrated
      that the ANP and BNP genes are tightly linked on mouse chromosome 4 and on the
      distal short arm of human chromosome 1. However, the precise physical map of the
      ANP and BNP genes has never been elucidated. In the present study, we
      characterized the genomic DNA fragment containing the ANP and BNP genes in mice
      and humans. Three genomic DNA clones harboring the entire mouse BNP gene were
      isolated from a 129/Sv mouse genomic DNA library. Nucleotide sequence analysis
      revealed that a phage clone (lambda mBNP #3) contains at its 3'-end the 5'
      flanking region and the first 209-bp sequence of the first exon of the mouse ANP
      gene. In mice, the BNP gene was located about 12 kb upstream of the ANP gene. By
      polymerase chain reaction, we isolated an approximately 11-kb human genomic DNA
      fragment containing the third exon of the BNP gene and the first and second exons
      of the ANP gene. In humans, the BNP gene was located upstream of the ANP gene,
      approximately 8 kb apart. The present study provides the direct evidence that the
      ANP and BNP genes are organized in tandem in the mouse and human genomes.

PMID- 8877791
TI  - Effect of treppe on isovolumic function in the isolated blood-perfused mouse
      heart.
AB  - The effects of treppe on left ventricular function in the isolated mouse heart
      perfused with physiological buffer or with erythrocyte-rich buffer were compared.
      Left ventricular systolic and diastolic pressures were measured in the
      isovolumically contracting (balloon in the left ventricle) mouse hearts. Hearts
      were isolated from 12 adult Swiss-Webster mice and perfused at constant pressure
      (approximately 85 mmHg) via the aorta. Perfusate consisted of non-recirculating
      oxygenated Krebs-Henseleit (KH) solution without or with washed cow red blood
      cells at a hematocrit of 20% (KH-RBC20). The measured ionized calcium
      concentration of the perfusates were adjusted to 2.2 mmol/l and the temperature
      held constant at 37 degrees C. Left ventricular systolic pressure, its derivative
      and diastolic pressures were recorded via a pressure transducer attached to a
      small latex balloon which was placed in the left ventricle through a left atrial
      incision. The balloon volume was adjusted to achieve an end-diastolic pressure of
      4-8 mmHg. Left ventricular (LV) developed pressure averaged 111 +/- 4 (mean +/-
      S.E.M.) with KH alone and 108 +/- 4 mmHg with KH-RBC20 while the coronary flows
      were 3.1 +/- 0.18 and 0.95 +/- 0.15 ml/min respectively. In both KH solution
      alone and KH-RBC20, developed pressure remained relatively stable from 3 to 5 Hz
      while +/- dp/dt increased approximately 10% above values observed at 3 Hz. During
      KH perfusion with increasing stimulation rates, left ventricular pressure and +/-
      dP/dt, to a lesser extent, decreased while end-diastolic pressure markedly
      increased at stimulation rates higher than 5 Hz. However, KH-RBC20 perfusion
      prevented the marked increase in diastolic pressure with increasing stimulation
      rates (from 5 to 10 Hz). No significant difference in left ventricular developed
      pressure or +/dP/dt response to treppe were in evidence between groups. These
      results demonstrate that diastolic function of the isovolumically contracting
      mouse heart is sensitive to treppe and different techniques of perfusion. Buffer
      perfusion alone may limit accurate measurement of left ventricular diastolic
      properties and exacerbate changes in diastolic function, particularly under
      conditions of increased oxygen demand. The erythrocyte perfused mouse heart
      provides an in vitro model for determining cardiac function which is
      physiologically superior to buffer perfusion, and may be useful to investigators
      to assess gene influence on left ventricular function in genetically altered
      mice.

PMID- 8877792
TI  - Organization of the mouse cardiac natriuretic peptide locus encoding BNP and ANP.
AB  - The genes encoding the mouse atrial natriuretic peptide and B-type natriuretic
      peptide were previously shown to be physically linked on mouse chromosome 4
      (Steinhelper ME, 1993, Structure, expression, and genomic mapping of the mouse
      natriuretic peptide type-B gene. Circ Res 72: 984-992). In the present study the
      spatial relationship and orientation of the mouse atrial natriuretic peptide and
      B-type natriuretic peptide transcription units were identified and a physical map
      of the mouse cardiac natriuretic peptide locus was obtained. To this end, genomic
      clones encoding atrial natriuretic peptide and B-type natriuretic peptide were
      isolated from a mouse genomic library in bacteriophage P1. Three independent
      clones encoding atrial natriuretic peptide were isolated and two of these also
      encode B-type natriuretic peptide. Both transcripts were shown to arise from the
      same DNA strand, with B-type natriuretic peptide encoded approximately 15 kb 5'
      of atrial natriuretic peptide based on field inversion gel electrophoresis of
      fragments amplified with specific oligonucleotides. This finding was confirmed by
      isolation of subclones comprising the entire locus and by blot hybridization
      analysis of mouse genomic DNA. The results show that the genes encoding the two
      natriuretic peptides expressed predominantly in mammalian cardiac myocytes are
      organized in tandem on mouse chromosome 4. This information provides a physical
      framework for investigating mechanisms that regulate transcription of the cardiac
      natriuretic peptide locus.

PMID- 8877793
TI  - Altered interactions among thin filament proteins modulate cardiac function: a
      clarification.

PMID- 8877794
TI  - Molecular recognition in drug discovery. A special issue based on the 36th annual
      Buffalo Medicinal Chemistry Symposium.

PMID- 8877795
TI  - Molecular recognition by natural macrocycles. I. d-tubocurarine as a host
      molecule for organic anions.
AB  - The binding of 8-anilino-1-naphthalenesulfonate and 15 anions of substituted
      benzoic, aliphatic dicarboxylic, and N-acetyl-alpha-amino acids to a macrocyclic
      alkaloid d-tubocurarine in aqueous solution has been studied by fluorometry,
      conductometry, and 1H NMR. The binding constants vary from ca. 50 to 3300 M-1
      depending on the guest structure, charge and hydrophobicity. The results of
      fluorescence and NMR studies show that the host-guest complexation of the anions
      of aromatic acids involves the formation of a salt bridge between the quaternary
      nitrogen of the alkaloid and the anionic group of the guest as well as
      hydrophobic/Van der Waals interactions between the guest and host aromatic
      moieties. The binding of dianions of aliphatic dicarboxylic acids most probably
      is purely electrostatic. In general, d-tubocurarine possesses binding ability
      comparable to that of synthetic cyclophanes. It binds enantiospecifically anions
      of N-acetyl-alpha-amino acids and discriminates between positional isomers of
      anions of hydroxy and carboxy substituted benzoic acids.

PMID- 8877796
TI  - Molecular interaction analysis in ligand design using mass transport, kinetic and
      thermodynamic methods.
AB  - Ligand design in biotechnology is underpinned by the control of molecular
      affinity. Hence, measuring binding interactions is a key component in designing
      ligands for such uses as therapeutics, diagnostics, biomaterials and separation
      science. Mass transport, kinetic and thermodynamic methods have been used for
      macromolecular interaction analysis but also have potential applicability as
      direct methods for measuring small molecular interactions. They can enhance the
      ligand design process by providing the ability to choose ligands based on both
      their kinetic and thermodynamic binding properties.

PMID- 8877797
TI  - Specific targeting of protein-DNA complexes by DNA-reactive drugs (+)-CC-1065 and
      pluramycins.
AB  - To gain insight into the interactions between transcriptional factor proteins and
      DNA, the DNA-reactive drugs (+)-CC-1065 and pluramycin were used to target
      specific protein-DNA complexes. The structural features of the complex between
      the transcriptional activator Sp1 and the 21-base-pair repeat of the early
      promoter region of SV40 DNA were examined using hydroxyl-radical footprinting;
      (+)-CC-1065, a sequence-specific minor groove bending probe; and circularization
      experiments. The results show that the 21-base-pair repeat region has an
      intrinsically in-phase bent structure that is stabilized upon saturation Sp1
      binding by protein-DNA and protein-protein interactions to produce a looping
      structure. The intercalating drug pluramycin was used to probe the structural
      details of the interaction between the TATA binding protein (TBP) and the TATA
      box DNA sequence. TBP, which directs initiation of RNA transcription, exhibits
      two-fold symmetry and apparently interacts with the TATA box in a symmetrical
      fashion. However, the interaction results in an asymmetric effect, in that
      transcription is initiated only in the downstream direction. Using pluramycin as
      a probe, it was determined that TBP binding to the human myoglobin TATA sequences
      enhances pluramycin reactivity at a site immediately downstream of the TATA box.
      The implications on transcriptional control of ternary complexes comprised of
      transcriptional factors, DNA, and DNA-reactive compounds will be presented.

PMID- 8877798
TI  - The "n' effect in molecular recognition.
AB  - The cooperativity which exists in crystal melting and many biological molecular
      recognition phenomena arises from extended arrays of weak interactions. We
      present a correlation between the melting temperature of a crystal and the
      intermolecular energy (which is evident only when compounds possessing several or
      many internal rotors are excluded). The correlation is used as the basis for a
      model of crystal melting which is capable of estimating the melting temperature
      of crystals. This model provides the basis for an understanding of the sharpness
      of the crystal melting transition for organic and inorganic substances. The
      cooperativity illustrated by the extended arrays of weak interactions, or the "n'
      effect, is extended to analogous order/disorder transitions in biological
      systems, such as the "melting' of DNA and RNA duplexes, providing insights into
      the physical properties of these structures.

PMID- 8877799
TI  - A molecular dynamics study of the three-dimensional model of human synovial fluid
      phospholipase A2--transition state mimic complexes.
AB  - Different modes of binding of transition state mimics: amide, phosphonate and
      difluoro ketone, to human synovial fluid phospholipase A2 (HSF PLA2) are studies
      by molecular dynamics simulations computed in solvent. The results are analysed
      in the light of primary binding sites. Hydrogen bonding interaction plays an
      important role for amino acids such as Gly32, Val30, and Glu55, apart from the
      well known active site residues viz Asp48, Gly25, Gly29, Gly31, His27, His47,
      Lys62, Phe23, Asn114 and Tyr112. In addition, the hydrogen bonding interaction
      between Sn-1 tetrahedral phosphonate group of amide and difluoro ketone
      inhibitors and crystallographic water molecules (H2O 523, H2O 524 and H2O 401)
      seems to have a significant role. Many of the active site charged residues
      display considerable movement upon ligand binding. The structural effects of
      ligand binding were analyzed from RMS deviations of C alpha in the resulting
      energy-minimized average structures of the receptor-ligand complexes. The values
      of the RMS deviations differ among the HSF PLA2s, in a pattern that is not the
      same for the three complexes. This suggests that ligands with different
      pharmacological efficacies induce different types of conformational changes of
      the receptor. Our active-orientation model is, at least qualitatively, consistent
      with experimental data and should be useful for the rational design of more
      potent inhibitors.

PMID- 8877800
TI  - A technique to study molecular recognition in drug design: preliminary
      application of free energy derivatives to inhibition of a malarial cysteine
      protease.
AB  - We present molecular dynamics studies on model complexes of inhibitors of a
      malarial cysteine protease. The initial model for such complexes came from the
      model building of the protein using its homology with other cysteine proteases
      and calculations using DOCK to generate new lead compounds. Some of the initial
      model-built structures were quite stable for 100 psec of dynamics; others moved
      significantly from their model-built orientation. We also calculated the free
      energy derivatives at each atom in the inhibitor, both in water and in the
      binding site. The results of these calculations suggest directions for the design
      of new, more potent enzyme inhibitors and agree qualitatively with some of the
      experimental findings. Nonetheless, we stress that we have only used this
      methodology in an interpretive rather than a predictive manner.

PMID- 8877801
TI  - Seeing double: crystal structures of the type I TNF receptor.
AB  - The crystal structure of the extracellular domain of the type I tumor necrosis
      factor receptor (sTNF-R1) has been determined to 2.25 A at pH 7.5. We have also
      solved the structure of sTNF-R1 at pH 3.7. sTNF-R1 is an elongated molecule
      consisting of a linear combination of four cysteine-rich motifs. Interestingly,
      the crystal structure reveals two distinct dimers of the receptor. One dimer is
      formed by a parallel arrangement of receptors, the other by an antiparallel
      arrangement of receptors. In the parallel arrangement of the receptors, the tumor
      necrosis factor (TNF) binding face of the receptor is completely exposed to
      solvent. However, in the antiparallel arrangement, the TNF binding face is
      intimately involved in the dimer interactions. Details of these recognition
      surfaces are discussed. Both these dimer interactions bury substantial surface
      area, comprise polar and apolar contact surfaces and have complimentary
      recognition surfaces. Thus these interactions are typical of genuine protein
      protein interactions, rather than crystal packing contacts. These dimers may
      function to inhibit signal transduction in the absence of TNF or in the case of
      the parallel dimer, promote clustering of TNF/TNF receptor complexes on the cell
      surface.

PMID- 8877802
TI  - Comparative in vivo sensitizing efficacy of porphyrin and chlorin dimers joined
      with ester, ether, carbon-carbon or amide bonds.
AB  - The anti-cancer activity of dimers joined with ether, ester or carbon-carbon
      bonds by photodynamic therapy (PDT) was compared by using DBA/2 mice transplanted
      with SMT/F tumors. Dimers with ether and carbon-carbon linkages were found to be
      more effective than those linked with ester bonds. Variation of the substituents
      at peripheral positions made a significant difference in in vivo efficacy. Among
      the ether and carbon-carbon linked dimers, the divinyl analogs were found to be
      most effective. The preliminary in vivo results also suggest that the position(s)
      of the hydrophilic substituents in the molecules make a remarkable difference in
      photosensitizing activity. An unsymmetrical dimer with an amide linkage, obtained
      from 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) was found to be less
      effective than HPPH.

PMID- 8877803
TI  - Experimental results from host-guest complexes for the design of effectors in
      biological systems and of enzyme analogous catalysts.
AB  - Strategies and results for the extraction of biologically important non-covalent
      binding increments from studies of synthetic host-guest complexes are described
      with selected examples. Systematic analyses of association constants and the
      corresponding complex conformation in solution allows us to assign specific
      values to different pairwise interactions, including salt bridges, amide-type
      hydrogen bonds, van der Waals effects, and metal ion interactions. A comparison
      of association constants between selected flexible and rigid ion pairs shows few
      differences, indicating that different entropy contributions either are small, or
      cancel with corresponding enthalpy changes, at least in weakly bound complexes.
      The supramolecular design of enzyme-analogous catalysts is illustrated with
      complexes containing, e.g. strongly bound yet still active Ln3+ ions, e.g. in an
      azacrown ether, and groups which support association with nucleic acids and can
      serve as nucleophiles. The experimentally observed hydrolysis rate enhancements
      with such artificial nucleases amount to 10(6) and more, both with phenyl
      phosphates and with ds-DNA.

PMID- 8877804
TI  - Molecular similarity analysis on biologically active macrocyclic bis(bibenzyls).
AB  - Conformational analysis of marchantin A (1), a bis(diarylether) type, and
      riccardin A (2), a diarylether-biphenyl type macrocyclic bis(bibenzyl) was
      carried out by systematic unbounded multiple minimum search (SUMM). Mobility of
      the macrocyclic rings was analysed by variable temperature 1H-NMR study.
      Molecular similarity analysis was performed on the minimum energy conformers of 1
      and 2 comparing their steric, electrostatic and hydrophobic properties.
      Correlation between complexation properties and calmodulin inhibitor activity was
      established. Differences in steric and electrostatic profiles may be responsible
      for the reduced Ca2+ affinity and activity of 2.

PMID- 8877805
TI  - Inhibitors of HIV protease: unique non-peptide active site templates.
AB  - New templates were designed and prepared which straddle the active site of HIV-1
      protease. These templates were designed to be "flexible scaffolds' upon which
      substituents could be appended to fill the pockets of HIV protease. The new
      templates prepared and analysed were 4-hydroxy-5H-furan-2-ones, 4-hydroxy-5,6
      dihydropyrones, 3-hydroxy-cyclohex-2-enones, and 4-hydroxy-2(1H)-pyridinones, of
      which the 4-hydroxy-5,6-dihydropyrones were found to be the most potent
      inhibitors of HIV-1 protease.

PMID- 8877806
TI  - Hydrophobic vs coulombic interactions in the binding of steroidal polyamines to
      DNA.
AB  - Seven new steroidal polyamines derived from bile acids, either lithocholic or
      deoxycholic acid, have been studied as DNA-binding agents using four
      complimentary methods: an ethidium displacement assay, observed changes in the
      thermal denaturation of poly[d(AT)], effects on hyperchromicity of DNA, and
      circular dichroism. In addition, modelling studies were conducted to examine the
      electrostatic surface potential of the polycations. The results point to a key
      role for a large hydrophobic surface area on the steroid in addition to the
      Coulombic attraction by ammonium and guanidinium groups on the steroid
      interacting with the polyphosphate backbone.

PMID- 8877807
TI  - Molecular recognition with C-clamp porphyrins: synthesis, structural, and
      complexation studies.
AB  - Porphyrin-based molecular clefts equipped with a strategically positioned
      carboxylic group have been synthesized. These ditopic porphyrins exhibit
      excellent binding affinity for many neutral substrates. X-ray structures of a
      porphyrin-water inclusion complex and a Zn(porphyrin)-methanol complex reveal how
      the carboxylic group interacts with substrates via H-bonding. Multipoint
      recognition is demonstrated in the differential binding of 1,2,3- versus 1,2,4
      triazole, suggesting the possible use of such receptors to separate heterocyclic
      bases.

PMID- 8877808
TI  - Model systems for flavoenzyme activity. The effects of specific hydrogen bonds on
      the 13C and 1H NMR of flavins.
AB  - We have developed a family of receptors designed to bind flavin derivatives using
      specific hydrogen bond interactions. These synthetic host molecules provide a
      model for specific flavoenzyme-cofactor interactions, allowing isolation and
      observation of the effects of hydrogen bonding on flavin NMR. We describe here
      the use of one of these receptors to study the effects of hydrogen bonding to
      O(2), N(3), and O(4) on flavin 1H and 13C NMR.

PMID- 8877809
TI  - All D-amino acid hexapeptide inhibitors of melittin's cytolytic activity derived
      from synthetic combinatorial libraries.
AB  - The identification of peptides that inhibit the biological functions of proteins
      was used as a means to explore protein/ligand interactions involved in molecular
      recognition processes. This approach is based on the use of synthetic
      combinatorial libraries (SCLs) for the rapid identification of individual
      peptides that block the interaction of proteins with their biological targets.
      Thus, each peptide mixture of an all-D-amino acid hexapeptide SCL in a positional
      scanning format was screened for its ability to inhibit the hemolytic activity of
      melittin, a model self-assembling protein. The potent inhibitory activity of the
      identified individual peptides suggests that protein-like complexes are able to
      specifically bind to peptides having an all-D configuration. These results also
      show that SCLs are useful for the identification of short, non-hydrolysable
      sequences having potential intracellular inhibitory activities.

PMID- 8877810
TI  - Novel nonclassical inhibitors of glycinamide ribonucleotide formyltransferase: 10
      formyl and 10-hydroxymethyl derivatives of 5,8,10-trideazapteroic acid.
AB  - Several new 10-formyl and 10-hydroxymethyl derivatives of 5,8,10-trideazapteroic
      acid have been synthesized by a novel and convenient enamine alkylation
      procedure. Two of these compounds (10a and 10b) were shown to be very powerful
      inhibitors of L. casei (10a, IC50 = 8 x 10(-6) M; 10b, IC50 = 7 x 10(-6) M) and
      recombinant mouse (10a, IC50 = 3.4 x 10(-5) M; 10b, IC50 = 2.8 x 10(-5) M)
      glycinamide ribonucleotide formyltransferase (GARFT). These IC50 values are
      comparable to the classical GARFT inhibitor (6R)-DDATHF (IC50, L. casei 2.3 x 10(
      6)M; recombinant mouse 2.3 x 10(-5) M) under identical assay conditions. For both
      compounds, the inhibition of L. casei GARFT increased with time of incubation,
      but not markedly with the recombinant mouse enzyme. Due to their potential
      ability to interfere with purine biosynthesis and to penetrate microbial cells
      the new nonclassical GARFT inhibitors reported here may be useful for the
      treatment of infections caused by microorganisms that are sensitive and resistant
      to conventional antimicrobial agents.

PMID- 8877811
TI  - Molecular docking towards drug discovery.
AB  - Fueled by advances in molecular structure determination, tools for structure
      based drug design are proliferating rapidly. Lead discovery through searching of
      ligand databases with molecular docking techniques represents an attractive
      alternative to high-throughout random screening. The size of commercial databases
      imposes severe computational constraints on molecular docking, compromising the
      level of calculational detail permitted for each putative ligand. We describe
      alternative philosophies for docking which effectively address this challenge.
      With respect to the dynamic aspects of molecular recognition, these strategies
      lie along a spectrum of models bounded by the Lock-and-Key and Induced-Fit
      theories for ligand binding. We explore the potential of a rigid model in
      exploiting species specificity and of a tolerant model in predicting absolute
      ligand binding affinity. Current molecular docking methods are limited primarily
      by their ability to rank docked complexes; we therefore place particular emphasis
      on this aspect of the problem throughout our validation of docking strategies.

PMID- 8877812
TI  - Design and analysis of RNA structure-specific agents as potential antivirals.
AB  - A number of pathogenic RNA viruses, such as HIV-1, have extensive folded RNA
      conformations with imperfect A-form duplexes that are essential for virus
      function, and could serve as targets for structure-specific antiviral drugs. A
      method for the discovery of such drugs involves evaluation of the interactions
      with RNA of a wide variety of compounds that are known to bind to nucleic acids
      by different mechanisms. This approach has been initiated by using corresponding
      sequence RNA and DNA polymers as initial test systems for analysis of RNA binding
      strength and selectivity. Compounds that bind exclusively in the minor groove in
      AT sequences of DNA do not have significant interactions with RNA. Polycations,
      however, can show significant RNA affinity and binding selectivity, probably
      through complex formation in the RNA major groove. Some intercalators and a group
      of diphenylfuran cations have strong interactions with RNA that are very
      dependent on compound structure. RNA hairpin model systems for the RRE binding
      site of HIV-1 Rev protein were constructed for more detailed investigations. The
      diphenylfuran cations bind strongly to RRE and selectively inhibit Rev binding.
      CD, NMR, and fluorescence binding studies indicate that the active compounds bind
      in the internal loop region of RRE (with binding constants > 10(7)M-1), and cause
      a conformational change in the RNA. None of the standard nucleic acid binding
      modes appears to fit the results for complexes of the active compounds with RRE,
      and it is proposed that the diphenylfuran system threads through the internal
      loop region of RRE. Such a model allows contacts of the furan cationic
      substituents with both grooves of RRE in addition to the intercalation
      interactions with the bases.

PMID- 8877813
TI  - Inhibition of phosphatidylinositol-specific phospholipase C: studies on synthetic
      substrates, inhibitors and a synthetic enzyme.
AB  - Enzyme inhibition studies on phosphatidylinositol-specific phospholipase C (PI
      PLC) from B. Cereus were performed in order to gain an understanding of the
      mechanism of the PI-PLC family of enzymes and to aid inhibitor design. Inhibition
      studies on two synthetic cyclic phosphonate analogues (1,2) of inositol cyclic
      1:2-monophosphate (cIP), glycerol-2-phosphate and vanadate were performed using
      natural phosphatidylinositol (PI) substrate in Triton X100 co-micelles and an NMR
      assay. Further inhibition studies on PI-PLC from B. Cereus were performed using a
      chromogenic, synthetic PI analogue (DPG-PI), an HPLC assay and Aerosol-OT (AOT),
      phytic acid and vanadate as inhibitors. For purposes of comparison, a model PI
      PLC enzyme system was developed employing a synthetic Cu(II)-metallomicelle and a
      further synthetic PI analogue (IPP-PI). The studies employing natural PI
      substrate in Triton X100 co-micelles and synthetic DPG-PI in the absence of
      surfactant indicate three classes of PI-PLC inhibitors: (1) active-site directed
      inhibitors (e.g. 1,2); (2) water-soluble polyanions (e.g. tetravanadate, phytic
      acid); (3) surfactant anions (e.g. AOT). Three modes of molecular recognition are
      indicated to be important: (1) active site molecular recognition; (2) recognition
      at an anion-recognition site which may be the active site, and; (3) interfacial
      (or hydrophobic) recognition which may be exploited to increase affinity for the
      anion-recognition site in anionic surfactants such as AOT. The most potent
      inhibition of PI-PLC was observed by tetravanadate and AOT. The metallomicelle
      model system was observed to mimic PI-PLC in reproducing transesterification of
      the PI analogue substrate to yield cIP as product and in showing inhibition by
      phytic acid and AOT.

PMID- 8877814
TI  - Melatonin receptors are present in non-optic regions of the brain of a deep-sea
      fish living in the absence of solar light.
AB  - Pineal melatonin hormonally transduces photoperiod to influence daily and
      seasonal cycles in most vertebrates (1, 2). Evidence of melatonin receptors
      throughout the brain of several fish species (3-5), particularly in
      retinorecipient structures, also indicates a role in visual processing. Despite
      the absence of solar light many deepsea organisms show seasonality (6-8). The
      presence of central melatonin receptors was investigated by quantitative in vitro
      autoradiography in the deep-sea fish Coryphaenoides (Nematonurus) armatus.
      Specific, time-dependent, saturable, high affinity and guanine nucleotide
      sensitive, 2-[125I]iodomelatonin binding was found over the mid-brain tegmentum
      and hindbrain. Competing ligand potency was iodomelatonin > melatonin >> 5-HT.
      Although C.(N.) armatus has well developed eyes no 2-[125I]iodomelatonin binding
      occurred in optic tectum, cerebellum or hypothalamus. Thus melatonin involvement
      in processing of visual information and control of seasonal physiology via
      hypothalamic areas appears to be absent in this species. The presence of central
      G-protein coupled receptors indicates a function for melatonin unrelated to solar
      light.

PMID- 8877815
TI  - Mortyn Jones Memorial Lecture--1995. Calcium checks cyclic AMP--corticosteroid
      feedback in adenohypophysial corticotrophs.
AB  - This paper summarizes a particular aspect of the stress response-the negative
      feedback control of anterior pituitary adrenocorticotrophin secretion with
      special focus on the mechanism of action of protein(s) rapidly induced by
      glucocorticoids. The main thesis is that the principal intracellular mechanism
      underlying corticosteroid inhibition of corticotroph secretory function is the
      opposition of cAMP-mediated activation by calcium ions. An increase of
      intracellular cAMP levels in corticotrophs produces a rise in intracellular free
      Ca2+ known to be essential for triggering hormone secretion. In parallel, calcium
      regulates agonist-induced cAMP accumulation through inhibition of adenylyl
      cyclase and the stimulation of cAMP-degrading phosphodiesterase. Furthermore, a
      key action of cAMP is the inhibition of a slow, sustained potassium current which
      is activated by calcium ions. Collectively, the actions of calcium constitute a
      powerful intracellular feedback inhibition of cAMP-induced cellular activation.
      Analysis of corticosteroid action in mouse corticotroph tumour (AtT20) cells
      indicates that the essence of corticosteroid feedback inhibition is the
      amplification of intracellular calcium feedback. A common mediator of the
      inhibitory actions of calcium may be the calcium receptor protein calmodulin the
      de novo synthesis of which is rapidly stimulated by glucocorticoid hormones.
      Targets of glucocorticoid-induced calmodulin may include the protein phosphatase
      calcineurin, calmodulin-activated phosphodiesterase(s), and BK-type potassium
      channels. The net result of calcium feedback inhibition is a reduction of Ca2+
      available for the facilitation of secretory activity i.e. calcium-induced
      desensitization. It is proposed that the intracellular calcium feedback loop
      outlined above also operates in the CNS components of negative corticosteroid
      feedback. A personal note: Professor Mortyn Jones introduced me to this field of
      research. His open-minded and critical approach to experimental work has always
      remained a guiding principle for my own efforts, and I hope that this paper which
      is dedicated to his memory will be found worthy of its purpose.

PMID- 8877816
TI  - Efferent projections from the ovarian steroid receptor-containing area of the
      ventrolateral hypothalamus in female guinea pigs.
AB  - The ventrolateral hypothalamus (VLH) in female guinea pigs includes a subset of
      neurons which contain estrogen and progestin receptors, and which are implicated
      in the regulation of female sexual behavior by steroid hormones. However, little
      is known about where these neurons project, and consequently which other brain
      areas are involved in sexual behavior in female guinea pigs. The anterograde
      tracer Phaseolus vulgaris-Leucoagglutinin was used to label efferents from the
      ovarian steroid receptor-containing part of the VLH. To identify the correct
      placement of the tracer specifically within the group of neurons containing
      estrogen receptors, medial hypothalamic sections were also immunostained for
      estrogen receptors. Forebrain areas receiving dense projections from the
      ventrolateral hypothalamus included the bed nucleus of the stria terminalis,
      medial preoptic area, anterior hypothalamic area, anterior ventromedial
      hypothalamus, and caudal ventrolateral hypothalamus. The midbrain central gray
      was also heavily labeled. Moderate innervation was observed in the forebrain in
      the basolateral amygdala, medial preoptic nucleus, lateroanterior hypothalamic
      nucleus, dorsal hypothalamic areas, posterior hypothalamus, zona incerta, and in
      the midbrain interspersed among the central and lateral tegmental tracts. The
      major efferent pathways from the VLH appeared to travel rostrally through the
      mediobasal hypothalamus and preoptic area, and caudally via the medial thalamic
      nuclei and periventricular fiber system. These findings are similar to those of
      previous studies tracing the efferents from the ventromedial nucleus in rats and
      from the lateral hypothalamus in guinea pigs. Many of these areas that receive
      input from the steroid receptor rich area within the VLH are likely to be
      involved in the regulation of female sexual behavior.

PMID- 8877817
TI  - Identification and characterization of angiotensinIV binding sites in rat neurone
      and astrocyte cell cultures.
AB  - This study demonstrates the existence of the putative receptor for the
      hexapeptide (3-8) fragment of angiotensin II (AngIV) on rat astrocytes and
      neurons grown in cell culture. Binding of 125I-AngIV was saturable and distinct
      from that of the AngII receptor subtypes. Equilibrium binding was attained in 15
      min in astrocytes and 75 min in neurons at 22 degrees C. The bound peptide was
      confirmed by HPLC to be intact AngIV while the bound peptide was substantially
      degraded, even in the presence of peptidase inhibitors. Scatchard analysis of
      equilibrium binding was consistent with a two binding site model, revealing a
      high affinity and a low affinity binding site in both cell types. In neurons, the
      respective association constants (Ka) were 2.72 +/- 0.23 nM-1 and 727 +/- 354 nM
      1, with associated receptor densities of 109.30 +/- 58.87 and 1723 +/- 1167
      fmol/mg protein. Similar analyses in astrocytes gave Kas of 5.71 +/- 2.85 nM-1
      and 277 +/- 205 nM-1, and respective densities of 191.1 +/- 90.1 and 1425 +/-
      1250 fmol/mg protein. However, the quantitative reliability of these binding
      isotherms may be influenced by the degration of unbound peptide. Competitive
      binding analysis was used to determine the specificity of the receptor site, with
      the relative order of affinities being AngIV > AngIII > AngII(4-8), and no
      displacement by AngII, Iosartan and PD123319 in either neurons or astrocytes.
      Autoradiography with 125I-AngIV performed on neuronal cultures demonstrated that
      binding was confined to a subpopulation of the total cells. These data support
      the existence of a specific binding site for AngIV in both neurons and
      astrocytes, consistent with the properties of binding reported previously in the
      brain, and distinguish this site from the AngII receptor subtypes.

PMID- 8877818
TI  - Hydropathy profiles of predicted thyrotropin-releasing hormone precursors are
      highly conserved despite low similarity of primary structures.
AB  - Two types of cDNAs encoding thyrotropin-releasing hormone (TRH) precursors (TRH-A
      and TRH-B) were amplified from hypothalamic mRNA of sockeye salmon by reverse
      transcriptase-polymerase chain reaction (RT-PCR). The amplification was achieved
      using two primers which correspond to TRH progenitor sequence (Lys/Arg-Arg-Gln
      His-Pro-Gly-Lys/Arg-Arg). A full length cDNA encoding TRH-A was obtained by 5'-
      and 3'-RACE methods. It has a length of 1324 base pairs (bp) that contains
      sequences of 5' and 3' untranslated regions and an open reading frame of 259
      codons. The sockeye salmon TRH-A deduced from the nucleotide sequence tandemly
      contains 8 copies of TRH progenitor sequences. Another cDNA which encodes a part
      of TRH-B consists of 242 bp, and the sequence homology between TRH-A and -B cDNAs
      is 90%. The result of Southern blot analysis of sockeye and masu salmon genomic
      DNAs supported the evidence that there are at least two TRH genes in the
      salmonid. A RT-PCR analysis of TRH gene expression in various tissues of sockeye
      salmon showed that strong expression was observed only in the brain. The primary
      structure of the sockeye salmon TRH-A shares low similarity to those of human,
      rat and Xenopus TRH precursors (35, 27 and 44%, respectively). However, their
      hydropathy profiles were almost the same with each other. The profile of sockeye
      salmon TRH-A showed the presence of two discrete hydrophobic regions, one in the
      N-terminal region which corresponds to the signal peptide and the other in the C
      terminal region. All of the repetitive TRH progenitor sequences are included in
      three hydrophilic regions easily recognizable. The present results thus suggest
      that the three-dimensional structures of TRH precursors are highly conserved,
      although the primary structures of TRH precursors have diverged through the
      evolutionary pathway of vertebrates.

PMID- 8877819
TI  - Short stressor induced long-lasting increases of vasopressin stores in
      hypothalamic corticotropin-releasing hormone (CRH) neurons in adult rats.
AB  - Recently, we demonstrated that single administration of interleukin-1 beta (IL-1)
      to adult rats induces a long-lasting (weeks) increase of vasopressin (AVP) stores
      in terminals of CRH neurons in the external zone of the median eminence (ZEME).
      This is accompanied by hypersecretion of AVP into the pituitary portal
      circulation and long-lasting hyperresponsiveness of the hypothalamo-pituitary
      adrenal (HPA) axis to stressors. Here, we determine whether this form of
      plasticity of hypothalamic CRH neurons is specific for IL-1 or represents a
      general response to a stressor. Single exposure of rats to lipopolysaccharide
      (LPS), IL-1, brain surgery or electric footshocks increases the AVP stores in the
      ZEME 7 and 11 days later. Exposure to insulin or ether does not affect the AVP
      stores. The stressors have little or no effect on the CRH stores in the ZEME. The
      amplitude of the increase in AVP as measured 7-11 days after stimulation
      correlates with the overall ACTH response to the stressor (area under curve, r =
      0.89, P < 0.0001), with the peak ACTH levels (r = 0.52, P < 0.05), but not with
      the duration of the ACTH response nor with any parameter of the corticosterone
      response. Administration of ACTH or corticosterone at doses that mimic stress
      induced plasma levels does not increase AVP stores 7 days later. We conclude that
      long-lasting increases of AVP stores in CRH terminals in the ZEME can be induced
      by various stressors and postulate that the amplitude of such increases depends
      on the degree of activation of the CRH neurons by the stressor. (NWO grant: 900
      543-101.)

PMID- 8877820
TI  - Prostaglandin E2 acts via the hypothalamus to stimulate ACTH secretion in the
      fetal sheep.
AB  - Prostaglandin (PG) E2 is secreted into the fetal circulation during late
      gestation in the sheep. Exogenous infusion of PGE2 is associated with robust
      increases in the circulating concentrations of ACTH and cortisol and it has
      therefore been proposed that endogenous PGE2 modulates the activity of the fetal
      HPA axis, which is the primary determinant of parturition and essential for the
      maturation of vital organ systems. The sites of action of PGE2 within the HPA
      axis have not been clearly established. We have compared the effects of PGE2
      infusion on ACTH and cortisol concentrations in intact fetuses and in those whose
      pituitaries were surgically disconnected from hypothalamic control (hypothalamo
      pituitary disconnected; HPD fetuses operated at 111-113 days gestational age).
      The effect of advancing gestational age on these responses was investigated by
      infusing PGE2 at 121, 131, 141 and 148 days of gestation. The functional
      integrity of the pituitary corticotrophs was tested by injecting CRH (1
      microgram) into intact and HPD fetuses at day 125. This test was repeated for the
      HPD fetuses at 160 days. The responsiveness of the adrenal glands was also tested
      by injecting 2.5 micrograms/kg synthetic ACTH1-24 (Synacthen) into both groups of
      fetuses at day 135, with the HPD group retested at day 155. PGE2 infusion was
      associated with a robust increase (P < 0.001) in plasma immunoreactive (ir) ACTH
      in intact fetuses at all gestational ages while HPD fetuses did not respond,
      except at day 148 when the response was small. Similarly, cortisol concentrations
      were increased (P < 0.001) during PGE2 infusion in intact fetuses but not in HPD
      fetuses, except for a minor increase at 148 days. The response of irACTH to
      exogenous CRH was similar in intact and HPD fetuses at 125 days and this response
      was maintained in HPD fetuses at day 160. The cortisol response of intact fetuses
      to ACTH1-24 exceeded that of HPD fetuses at day 135 and, in HPD fetuses, this
      response was unchanged when they were retested at 155 days, indicating that their
      adrenal responsiveness did not wane with time. We conclude that the effects of
      PGE2 on the fetal HPA axis are exerted predominantly or exclusively at a level
      above the pituitary gland.

PMID- 8877821
TI  - Molecular heterogeneity and glycosylation modulation of rat pituitary prolactin
      isoforms synthesized and secreted in vitro in postnatal ontogeny, gestation,
      lactation and weaning.
AB  - The modulation of both the molecular size heterogeneity and the relative
      distribution of rat prolactin variants, synthesized and secreted in vitro by rat
      pituitary cells in the course of postnatal ontogeny and in gestation, lactation
      and weaning was investigated by SDS-PAGE, immunoblotting, radioimmunological
      techniques and O-sialoendopeptidase digestion. The outcome of the experiments is
      as follows: 1) from day 1 of postnatal life 20-, 23-, 26-, 40-44 kDa and
      oligomeric rat prolactin isoforms were stored and secreted; 2) perinatal life is
      characterized by a high degree of variability of prolactin size isoforms and
      their respective repartition in storage and release; in addition to the major
      variants, transient ones of M, 25-, 28-, 33- and 36 kDa were secreted and/or
      stored; 3) O-sialoglycoprotease digestion of pituitary cell lysate gave good
      evidence for 25 kDa prolactin being a glycoform; 4) at 1 month of age 16 kDa rat
      prolactin appeared and persisted over the whole postnatal span (1 day-->1 year)
      but only in stored form; 5) the physiology of gestation was essentially
      characterized by the M(r)-modulation of the glycoform (26 kDa-->26.3 kDa) and the
      virtual absence of stored 26 kDa rat prolactin at week 1 of pregnancy; 6) in
      lactation and weaning uncommon multiple banding was observed in secreted
      oligomeric prolactin; 7) in pregnancy, lactation and weaning the differential
      distribution of released and stored prolactin isoforms displayed a considerable
      intra- and intervariability; 8) in the vast array of size isoforms observed in
      all our experiments monomeric 23 kDa prolactin was always the dominating variant.
      In conclusion, the molecular size heterogeneity and the differential distribution
      of secreted and stored rat pituitary prolactin is considerably influenced by age
      and physiological stimuli. The nature of polymeric prolactin and of the transient
      variants is presently unclear, and the exact physiological role of molecular
      heterogeneity modulation is unknown, both in humans and rat, but the patterns of
      change we observed in definite stages of life, suggest that this phenomenon is
      important in the maturation of the hypothalamus-pituitary axis and in the
      metabolic and hormonal changes accompanying gestation.

PMID- 8877822
TI  - Accreditation under siege.

PMID- 8877823
TI  - Academic outcomes and stress in full-time day and part-time evening baccalaureate
      nursing students.
AB  - This study examined differences in stress and academic outcomes in generic
      baccalaureate nursing students enrolled in a full-time day program and those
      enrolled in a part-time evening program. The study also sought to identify the
      relationship between stress and academic outcomes and between selected
      demographic variables and stress in these two groups of nursing students. Day and
      evening students did not differ on trait or state anxiety scores measured at the
      beginning of the semester; by mid-semester, state anxiety scores increased in
      evening students only. Nevertheless, no relationship between stress and academic
      outcomes was found in either group. Of the demographic variables examined, age
      and number of dependents were related to stress. There was no relationship
      between hours employed and stress scores. Students enrolled in an evening nursing
      program were able to achieve academic outcomes comparable to their day
      counterparts despite reporting greater stress and more hours spent in employment
      each week. The high stress reported by both day and evening students has
      implications for the development of support programs and stress reduction
      interventions in nursing schools.

PMID- 8877825
TI  - The effect of writing after reading on college nursing students' factual
      knowledge and synthesis of knowledge.
AB  - The purpose of this experimental study was to investigate the effect of writing
      after reading on factual knowledge and synthesis of knowledge. College sophomore
      nursing students (N = 118) were randomly assigned to one of three groups: a
      control group which read, reviewed, but did no writing; a notetaking group; or an
      essay writing group. A 10-item multiple-choice test of factual knowledge was
      given to all subjects immediately after completing each reading and writing task
      and again 7 days later. At the later time, each student also wrote an essay to
      demonstrate synthesis of knowledge. Seven days later, students repeated the same
      reading and writing activities with a second text. Results of ANOVA showed that
      notetaking was significantly better than essay writing or no writing for recall
      of facts. Essay writing, on the other hand, helped students synthesize better
      than notetaking. However, there was no difference between essay writing and no
      writing on synthesis of knowledge.

PMID- 8877824
TI  - Student/faculty practice and research in occupational health: health promotion
      and outcome evaluation.
AB  - Faculty strive to connect theory and practice with real life situations for
      students. This study evolved from student intervention with small industries as
      part of their undergraduate community health nursing clinical experience. A pre
      experimental static group design was used to explore the impact of health service
      availability on selected cardiovascular risk factors. Levels of health service:
      a) no service; b) student service; and c) formal health care service were
      compared. Chi-square, t-tests and MANOVA analyses supported three hypotheses that
      student intervention was equally as successful as formal health care service in
      reducing the selected cardiovascular risk factors of high weight to height
      ratios, blood pressure readings above 140/90 on three separate measurements,
      total cholesterol readings above accepted norms and a health risk profile which
      identifies risk for cardiovascular disease.

PMID- 8877826
TI  - Defining collegiality within the academic setting.
AB  - Faculty development and performance are important issues within colleges of
      nursing. Collegiality is a performance requirement for promotion and tenure, but
      the behaviors synonymous with collegiality are frequently unwritten within the
      academic community as well as being poorly defined in the literature. The
      ambiguity that this situation produces is often experienced by faculty seeking
      tenure and promotion. Faculty at a midwestern university used the Delphi
      technique to determine behaviors synonymous with collegiality. Results of the
      Delphi rounds yielded specific behavioral indicators for the four broad
      statements that describe collegiality in the governance document of the
      university. Those statements include willingness to serve on committees and
      perform work necessary to departmental operations, willingness to provide
      guidance and help colleagues in their professional duties, respect for the ideas
      of others, and conduct of one's professional life without prejudice toward
      others. Findings revealed that while the area of collegiality is ambiguous,
      indicators of collegial behavior can be identified. Limitations and benefits of
      using the Delphi technique are discussed.

PMID- 8877827
TI  - Home health care clinical experience: responding to the health care reform
      agenda.

PMID- 8877828
TI  - Using the telephone interview for evaluation of baccalaureate nursing programs.
AB  - Efficient use of the telephone is certainly relevant in the 20th century
      telecommunication age. A 20- to 30-minute phone call allows for interactive
      communication between the nurse educators and those who hire their graduates.
      Important information can be quickly obtained for assessing the outcomes of
      curriculum related to the perceived quality of nurse graduates practicing in
      various health care settings. This interview method was found to be efficient,
      convenient, and facilitated dynamic interchange. Feedback from respondents varied
      in their familiarity with the graduates and programs.

PMID- 8877829
TI  - The verbal connection: effective clinical teaching maximizing student
      communication skills.

PMID- 8877830
TI  - Planning for critical outcomes.

PMID- 8877831
TI  - Undergraduates' perceptions of their psychiatric practicum: positive and negative
      factors in inpatient and community experience.
AB  - To identify factors contributing to positive or negative undergraduate
      experiences, often cited as influencing student selection of practice area, 38
      baccalaureate students were queried about their inpatient/community psychiatric
      practicum. Positive, negative and potentially helpful factors were derived from
      the themes of their responses. Positive factors included staff's professionalism,
      enthusiasm and acceptance of students; diversity of learning opportunities; and
      direct involvement with patients. Negative factors related to nursing staff
      performance. Potentially helpful factors were those promoting goodness of fit
      between program expectations for students, characteristics of the clinical
      setting and modeling of psychiatric nursing career options.

PMID- 8877832
TI  - Factors associated with student success in a baccalaureate nursing program within
      an urban public university.

PMID- 8877833
TI  - Cells of flexor retinaculum in carpal tunnel syndrome.

PMID- 8877834
TI  - RADS after exposure to a riot-control agent: a case report.

PMID- 8877835
TI  - AOEC position paper on the organizational code for ethical conduct.

PMID- 8877836
TI  - Codes of ethics in occupational and environmental health.

PMID- 8877837
TI  - Occupation and risk of germ cell testicular cancer by histologic type in Ontario.
AB  - Incidence of both major histologic subgroups of germ cell testicular cancer,
      seminoma and nonseminoma, is increasing, but the etiology is largely unknown.
      Occupational clusters have been observed. In a case-control study in Ontario with
      495 incident cases and 974 population control subjects, jobs and industries were
      coded and analyzed. There is little evidence of occupational risk for all cases
      or for seminoma. Significantly increased risk of nonseminoma was associated with:
      miners (odds ratio [OR] = 12.39; 95% confidence interval [CI], 2.22 to 69.27),
      food and beverage processors (OR = 3.20; 95% CI, 1.39 to 7.35), utilities
      employees (OR = 3.15; 95% CI, 1.15 to 8.61), and other service workers (OR =
      1.05; 95% CI, 1.05 to 4.56). Leather-industry employees had elevated risk of
      nonseminoma (OR = 4.60; 95% CI, 0.75 to 28.28) consistent with a leather tannery
      cluster. Increased risk of nonseminoma among some workers can be explained if an
      additional event is required for converting seminoma to nonseminoma.

PMID- 8877838
TI  - Job satisfaction and perceptions of health.
AB  - Workers' perceptions of health have become one focus of research on the costs of
      health care, yet little is understood about the relationship between perceptions
      of health and perceptions of work. An exploratory cross-sectional study was
      conducted on a large southern university campus to determine if perceptions of
      select facets of work were related to perceptions of health. Results indicated
      that satisfactory perceptions of coworkers was the strongest predictor of current
      and future health perceptions, and the strongest predictor of perceptions of
      resistance to illness. Other significant job-facet predictors of health
      perceptions were autonomy, the work done on the present job, and pay.
      Satisfaction with supervision and opportunities for promotion were not predictive
      of health-perception measures. Implications for enhanced employee health include
      a greater emphasis on coworker relationships, especially in the current context
      of organizational change in business and industry.

PMID- 8877839
TI  - Prevalence of mood and anxiety disorders in a working population in Japan.
AB  - To learn the prevalence of mood and anxiety disorders (as defined by the
      Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised) in
      a working population in Japan, we analyzed data from a population-based survey.
      Among 140 respondents who had a job, 8% experienced any of seven mood and anxiety
      disorders in the past 6 months and 19% had in their lifetime. The 6-month and
      lifetime prevalence rates of major depressive episodes were 4% and 14%,
      respectively. The 6-month and lifetime prevalence rates of phobic disorders were
      both 4%. The lifetime prevalence rates for other anxiety disorders were 1% or
      less. The 6-month rate of any disorder, as well as 6-month and lifetime rates of
      phobic disorders, was higher in white-collar employees than in self-employed
      workers (P < 0.05). The multiple logistic regression confirmed the tendency after
      controlling for sex and age, although the result was not significant (P > 0.05).

PMID- 8877840
TI  - Pesticide application and increased dioxin body burden in male and female
      agricultural workers in China.
AB  - Large amounts of the powerful pesticide sodium pentachlorophenol (Na-PCP) salt
      have been sprayed over vast areas in central China to control schistosomiasis, a
      parasitic disease of epidemic proportions. Approximately 6000 tons of Na-PCP are
      produced in China annually. Dioxins, a class of toxic, persistent compounds, are
      found as impurities in commercial Na-PCP products. These contaminants are
      released into the environment and significantly contribute to human exposure to
      dioxins in China. This study was carried out to determine dioxin levels in
      environmental and human tissue samples from one schistosomiasis area to evaluate
      the health risks associated with exposure to Na-PCP. Na-PCP pesticide was applied
      in 1972, 1973, and again in 1978. A total of approximately 454 tons and 902 tons
      of 5-ppm Na-PCP in water were sprayed over large land and lake problem
      schistosomiasis areas, respectively. The groups studied were (1) sprayers or
      handlers of Na-PCP, (2) persons living in the sprayed areas, and (3) persons
      living in unsprayed areas 300 km north of the sprayed lake located in a city in
      the Jiangxi province. Individual whole-blood and breast-milk samples were
      collected and later pooled for dioxin analysis. Also, a sample of commercial Na
      PCP was collected. In addition, sediment samples from the lake where Na-PCP was
      sprayed were collected from four different sites and one control sample was
      collected from a non-schistosomiasis area. All of the samples were analyzed by
      high-resolution gas chromatography/mass spectrometry. A sample of Na-PCP used in
      schistosomiasis regions was analyzed and levels of 2,3,7,8-substituted
      dibenzodioxin (PCDD) and dibenzofuran (PCDF) congeners were measured. In
      addition, the international dioxin toxic equivalent (I-TEQ) value of this sample
      was calculated. Total I-TEQ of 162 parts per billion (ppb) was found in the
      Chinese Na-PCP product. A pooled breast-milk sample from mothers, female
      agricultural workers who were born in the schistosomiasis areas where large
      amounts of Na-PCP were sprayed, had an I-TEQ of 5,4 parts per trillion (ppt),
      lipid, which was about double that of mothers from control regions, women born in
      areas not sprayed with Na-PCP (2.6 ppt, lipid). The dioxin I-TEQ values in human
      blood ranged from 9.0 (subjects 15 to 19 years of age) to 16.3 ppt, lipid
      (subjects 35 to 70 years of age) in the whole-blood samples from Na-PCP exposed
      persons, whereas the general population's whole-blood I-TEQs were 4.8 and 6.4
      ppt, lipid, respectively. The PCDD/F congener distribution patterns in four
      sediment samples from schistosomiasis areas were similar to that of Na-PCP. By
      comparison of specific "fingerprint" congeners (higher chlorinated dioxins and
      the closely related dibenzofurans) in Na-PCP, human tissues, and sediment
      samples, we conclude that the chemical pesticide Na-PCP is a source of
      environmental and human dioxin exposure in the Chinese schistosomiasis area
      studied. Although human PCDD/F tissue levels in China are low compared with those
      in more industrialized countries, the elevated I-TEQ levels in exposed persons
      are cause for concern.

PMID- 8877841
TI  - Respiratory findings in workers not exposed to air pollutants.
AB  - The prevalences of acute and chronic respiratory symptoms and lung function
      changes were studied in a group of 806 workers working in a "clean environment."
      Acute symptoms during the work shift were reported by smokers but were
      essentially absent in nonsmokers. Chronic respiratory-symptom prevalences were
      similar to those reported in community-based populations, with smokers
      experiencing more chronic symptoms than nonsmokers. Baseline lung function
      measurements indicated no significant differences with values obtained from
      prediction equations based on community populations. There were significant
      across-shift increases in all ventilatory capacity tests (forced vital capacity,
      1-second forced expiratory volume, and maximum expiratory flow rates at 50% and
      the last 25% of the vital capacity) varying from +1.9% to +9.8% of the preshift
      values. Workers older than 40 years of age and those employed for more than 10
      years had similar across-shift changes compared with younger workers and those
      with longer durations of employment. Our data indicate that workers in clean work
      environments (with the exception of smokers) complain of few acute or chronic
      respiratory symptoms and have normal lung function. These workers experience
      increases in lung function across the work shift, probably reflecting normal
      diurnal variation. Smokers, although significantly more affected than nonsmokers,
      do not appear to have work-related findings, and smoking appears to be the most
      significant risk factor for the development of lung disease in unexposed workers.
      In this study, community-based control data was equivalent to worker control data
      in unexposed workers.

PMID- 8877842
TI  - Bloodborne pathogens risk and precautions among urban fire-rescue workers.
AB  - Health care workers are exposed to various infectious agents that can lead to
      disease transmission during patient care. Emergency first-responders, paramedics,
      and emergency medical technicians (EMTs) are a subgroup of health care workers
      particularly at risk for occupational exposure to bloodborne pathogens. The
      Centers for Disease Control and Prevention has recommended universal precautions
      to prevent occupational transmission of bloodborne pathogens among health care
      workers. This cross-sectional study evaluates risks and behaviors for
      occupational exposure to bloodborne pathogens among urban paramedics and EMTs in
      Dade County, Florida. Reported exposure via multiple routes was common,
      especially among paramedics. Knowledge of universal precautions was high, but
      reported practices were suboptimal because of inadequate information, as well as
      logistical and access issues. Additional research, administrative effort, and
      regulation are needed to increase the application of universal precautions in the
      prehospital setting.

PMID- 8877843
TI  - Wearing an abdominal belt increases diastolic blood pressure.
AB  - The purpose of this study was to determine the effect of wearing an abdominal
      belt on blood pressure (systolic and diastolic) and heart rate during a variety
      of tasks. The belt was typical of the elastic type with suspenders and Velcro
      tabs for cinching the belt snug. The tasks performed included sitting at rest,
      sitting with the torso inclined forward at 45 degrees, standing with the torso
      inclined forward at 45 degrees (with and without holding an 11-kg weight), a
      trunk axial rotation task, and squat lifting. Blood pressure was monitored
      noninvasively with a FINAPRES blood pressure monitor. Twenty healthy men
      performed each task with and without the abdominal belt. Although no significant
      increases in mean systolic blood pressure or heart rate were found, there was a
      significant increase in diastolic blood pressure in all conditions. All people
      considering wearing an abdominal belt should also consider the risks and
      liability associated with the additional cardiovascular load, particularly heart
      attack and stroke.

PMID- 8877844
TI  - Cigarette smoking at hire as a predictor of employment outcome.
AB  - We have reported that cigarette smoking at the time of hire is associated with
      elevated rates of accidents, injuries, absence, discipline, and firing among US
      postal workers. We followed this cohort of 2537 for a second year to assess
      whether these associations would change with time in a workplace with active
      smoking cessation programs. Smokers' elevated risks for accidents, injuries, and
      discipline decreased after the first year. Risk for involuntary turnover was
      slightly higher in the 2-year analysis. The elevation in the rate of absence for
      smokers remained comparable in both periods. Although it is possible that the
      decline in the relative risk of accidents, injuries, and discipline may reflect
      changes in smoking status, we were unable to obtain follow-up data on smoking
      status to test this hypothesis.

PMID- 8877845
TI  - Advances in biopharmaceutical analysis in the People's Republic of China: 1993
      1995.
AB  - Progress in biopharmaceutical analysis of drugs and their metabolites by liquid
      and gas chromatography between April 1993 and March 1995 has been reviewed. The
      evaluation and validation of these methods, as well as their applications in
      pharmacokinetics and metabolic studies, are also discussed.

PMID- 8877846
TI  - Interlaboratory study of log P determination by shake-flask and potentiometric
      methods.
AB  - The pKa and log P values of 23 structurally diverse compounds, including well
      known drugs and two pharmacons under development, were determined by
      potentiometry. Also, the log P data were measured by the shake-flask method. Many
      of the samples were investigated at both of the participating laboratories in
      order to evaluate the reproducibility of the pH-metric log P technique. The
      interlaboratory evaluation of pKa and log P data obtained by potentiometry showed
      excellent agreement (average delta pKa = +/-0.02 and delta log P = +/-0.07). The
      log P values obtained by the two different methods, ranging from -1.84 to 5.80
      (nearly eight orders of magnitude), were in very good concordance, as shown by
      the linear regression analysis: log PpH-metric = 0.9794 log Pshake-flask -0.0397
      (r = 0.9987, s = +/-0.091, F = 8153). The advantages of potentiometric log P
      determination are discussed.

PMID- 8877847
TI  - Near-infrared spectroscopic characterization of pharmaceutical powder blends.
AB  - Near-infrared (near-IR) spectroscopy was used to qualitatively assess the
      homogeneity of a typical direct compression pharmaceutical powder blend
      consisting of hydrochlorothiazide, fast-flo lactose, croscarmellose sodium, and
      magnesium stearate. Near-IR diffuse reflectance spectra were collected from
      thieved powder samples using a grating-based spectrometer. A second-derivative
      calculation and principal component analysis were performed on the spectra prior
      to qualitative evaluation. Blend homogeneity was determined using single- and
      multiple-sample bootstrap algorithms and traditional chi-square analysis. The
      results suggested that bootstrap techniques provided greater sensitivity for
      assessing blend homogeneity than chi-square calculations and that near-IR has
      great potential as an analytical tool in powder blend analysis.

PMID- 8877848
TI  - Effect of purification followed by solubilization of receptor material on
      quantitative receptor assays for anticholinergic drugs.
AB  - In order to optimize quantitative receptor assays for anticholinergics, the
      different receptor preparations resulting from the purification and the
      solubilization of the P2 pellet from the calf striatum were evaluated. The
      dissociation constants for two chemically different anticholinergics, the
      tertiary amine scopolamine and the quaternary amine oxyphenonium, were calculated
      from inhibition studies of 3H-NMS binding in buffer and plasma. The Kd values for
      both anticholinergics were similar for all the membrane-bound receptor
      preparations (unpurified and the purified P2 pellet) either in buffer or in
      plasma. More pronounced differences were observed between the membrane-bound and
      solubilized receptors. By introducing the solubilized receptor as well,
      differences between the individual anticholinergics appeared. On the one hand,
      for scopolamine, a gain in sensitivity of 1.5-2.8 in plasma was observed for the
      solubilized receptor. On the other hand, in the case of oxyphenonium, a dramatic
      loss in sensitivity (by a factor of about 24) was observed with the solubilized
      receptor, as compared to the membrane-bound receptor, in buffer. Very
      interestingly, however, when the solubilized receptor was used in plasma, a
      lowering of the Kd value was found for both anticholinergics, i.e. the assays
      became more sensitive. Such an effect (not observed for the membrane-bound
      receptor) could be obtained only when the percentage of digitonin present in the
      assay was at least 0.12% (w/v) or higher.

PMID- 8877849
TI  - Radioimmunoassay method for DX-9065a, an anticoagulant agent. Development,
      evaluation and application to human plasma.
AB  - A simple and sensitive radioimmunoassay (RIA) method was developed for
      determination of DX-9065a, (+)-(2S)-2[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]
      oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate, a
      newly synthesized anticoagulant agent. Immunogens were prepared by condensation
      of a hapten with bovine serum albumin via a carboxyl group. Antisera was obtained
      by immunization of five rabbits with immunogen. High-titer antisera was obtained
      from 2 rabbits immunized with immunogen. The sensitivity of this newly developed
      RIA method was 100-fold greater than that of a previously used conventional HPLC
      method. This method was validated for determination of human plasma samples in
      clinical trials. The cross-reactivities of employed antisera with three
      steroisomers (2R3R-, 2R3S- and 2S3R forms) were 0.7, 20.2 and 43.9% respectively.
      The effect of cross-reactivity of postulated stereoisomers in clinical samples
      was evaluated by a parallelism study using human plasma samples obtained after
      oral administration of the drug to healthy Japanese volunteers. Results showed no
      effect on measured concentration. From these data, this method showed suitable
      accuracy and precision for the pharmacokinetic evaluation of DX-9065a in clinical
      study. The method was applied to plasma samples obtained from a healthy Japanese
      volunteer who had orally received 12.85 mg (10 mg as DX-9065) of the drug. The
      maximum plasma concentration measured was 6.2 ng ml-1 1 h after administration.

PMID- 8877850
TI  - Rapid ultraviolet spectrophotometric determination of bronopol: application to
      raw material analysis and kinetic studies of bronopol degradation.
AB  - A simple and rapid spectrophotometric assay is described for bronopol
      determination in raw material. The method is based on the measurement of
      absorbance (at 244 nm) of bromonitroethanol (sodium salt of aci-form), the
      chromophoric derivative formed from bronopol instantaneously by a retroaldol
      reaction in the presence of 0.1 M NaOH. This derivative has a molar absorption
      coefficient of 8330 (at absorption maximum, 244 nm) and its absorbance follows a
      linear relationship with the concentration of bronopol within the range 5-25
      micrograms ml-1. It has been validated that the spectrophotometric method can be
      applied successfully to the analysis of bronopol in raw material. The sensitivity
      of the method towards bronopol degradation in aqueous solution is comparable to
      that obtained by gas-liquid chromatography and enzymatic assays described
      elsewhere. Thus the proposed method is suitable for use in the study of the
      kinetics of bronopol degradation. A simple and sensitive detection of bronopol
      and bromonitroethanol (down to 2 micrograms) on a silica gel 60 F254 precoated
      thin layer chromatography plate based on the formation of the chromophoric
      derivative in the presence of ammonia vapour has been described.

PMID- 8877852
TI  - Determination of dipyridamole by modified extraction-gravimetry with a surface
      acoustic wave resonator sensor.
AB  - A simple and sensitive extraction-gravimetric method for the determination of
      dipyridamole is presented. The method is based on the extraction of free
      dipyridamole with chloroform, after neutralization with a basic agent, followed
      by measurement of the frequency shift response of the specially designed surface
      acoustic wave resonator sensor after evaporation of the extractant from the
      surface of the resonator. The frequency shift response was proportional to the
      amount of dipyridamole in the range 0.065-1.12 micrograms. Experimental
      parameters and the effect of interfering substances on the assay of dipyridamole
      were also examined in this study. The method was applied to the determination of
      dipyridamole in tablets.

PMID- 8877851
TI  - In vitro bioassay for human erythropoietin based on proliferative stimulation of
      an erythroid cell line and analysis of carbohydrate-dependent microheterogeneity.
AB  - The human erythroleukemia cell line TF-1 was employed for the determination of
      proliferative stimulation induced by recombinant human erythropoietin (rhEpo).
      Potencies of various intact and sugar-trimmed rhEpo preparations were estimated
      using the International Standard for Human r-DNA-derived Epo (87/684) as a
      reference for activity. The cellular response was measured in a multi-channel
      photometer using a colorimetric microassay, based on the metabolism of the
      tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to
      formazan, by viable cells. The linear part of the log dose-response relationship
      encompassed 2.5-90 pM and activity of rhEpo preparations was measured at doses
      between 3 and 60 pM. The assay was designed as a parallel line test, using three
      or four concentrations for potency determinations, which fulfills pharmacopoeial
      requirements for assay validity. Inter-assay relative standard deviation varied
      between 4.1% and 12.6% and most assays revealed potencies with limits of error
      within 87-113%. In order to acquire an additional means for an efficient probing
      of physiologically relevant features of rhEpo, a luminiscence-dependent Western
      detection system, based on a combined isoelectric focusing/sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis separation, was established. As
      opposed to conventional electrophoresis the two dimensional approach enabled the
      disclosure of minor truncations in the rhEpo-attached glycan moieties using
      picomolar quantities of the hormone. Moreover, the separated isoforms of rhEpo
      were quantified by computer-assisted densitometry and compared with the 87/684
      standard. Accordingly, results obtained by the cellular response were balanced
      against the general pattern observed and the relative amounts of separated rhEpo
      isomers as determined by the quantitative Western analysis. The method described
      should be suitable for potency assessments of pharmaceutical formulations of
      rhEpo.

PMID- 8877853
TI  - Determination of vitamin C in effervescent tablets containing other vitamins
      together with trace elements.
AB  - A simple, rapid method is reported for the determination of vitamin C in
      effervescent tablets containing other vitamins and several trace elements such as
      Mg(II), Zn(II), Fe(II), Mn(II), Cu(II) and Mo(VI). The procedure was developed on
      the basis of the bromate ion-iodide ion-ascorbic acid clock reaction (Landolt
      reaction). Interference effects of air oxygen and metal ions and the role of pH
      are discussed in detail.

PMID- 8877854
TI  - Determination of pyridoxal in human serum by matrix isopotential synchronous
      fluorescence spectrometry.
AB  - The determination of pyridoxal in human serum was performed using a fluorimetric
      technique that is useful for the determination of compounds in samples with
      unknown background fluorescence, based on synchronous scans through a trajectory
      joining points of equal intensity of a fluorescence matrix three-dimensional
      spectrum. This technique, called matrix isopotential synchronous fluorescence can
      be improved by means of the application of derivatives. The determination of
      pyridoxal in human serum was performed with this technique without any prior
      separation steps. The validity, applicability and simplicity of the method were
      demonstrated. The measurements were performed in aqueous medium at pH 7.0
      adjusted by adding 0.05 M phosphate buffer solution. A complete statistical
      analysis of the experimental data was performed and the results showed that
      correlation coefficients are between 0.9901 and 0.9958 for all the calibration
      graphs, and in all cases the intercepts on the ordinate were negligible. The
      experimental F (1.72) is smaller than theoretical value (3.89) as expected from
      an analysis of variance. The reproducibility of the method was tested and the
      results were a standard deviation of 0.0117 microgram ml-1 and a relative error
      of 4.91%.

PMID- 8877855
TI  - Vibrational spectrometry for the assessment of active substance in metoprolol
      tablets: a comparison between transmission and diffuse reflectance near-infrared
      spectrometry.
AB  - Near-infrared spectrometry (NIR) was used to quantify metroprolol succinate in
      controlled release tablets. Metoprolol tablets were made according to an
      experimental design using different strengths around a central strength of 47.5
      mg per tablet. A comparison was made between NIR in the diffuse reflectance mode
      and the transmission mode. This showed that, although a narrower wavelength range
      was available in the transmission mode, predictions were much better for models
      based on transmission spectra than for models based on diffuse reflectance
      spectra. The main reason for this is that in the reflectance mode NIR
      spectrometry is very sensitive to the inhomogeneity of the material, while in the
      transmission mode this problem is less severe. This is due to the larger volume
      of the material scanned in the transmission mode compared to that in diffuse
      reflectance. Spectra were taken before and after the tablets were stored under
      humid conditions. This allowed the final calibration models to be made more
      robust towards variations in the amount of water in the tablet. Different batches
      of metoprolol pellets and microcrystalline cellulose were used during the
      production of the tablets. this resulted in models that were more robust towards
      possible batch-to-batch differences in the main constituents.

PMID- 8877856
TI  - Fluorimetric determination of chloroxine using manual and flow-injection methods.
AB  - A reliable and highly sensitive method is described for the determination of
      chloroxine in pharmaceutical preparations. It involves the formation of a complex
      between chloroxine and aluminum(III) in a micellar medium. The complex is a very
      fluorescent species, and there is a linear relationship between chloroxine
      concentration and fluorescence intensity over the range 2.0 x 10(-8)-5.1 x 10(-5)
      mol l-1. The limit of detection is 5 x 10(-9) mol l-1. The method can be easily
      adapted to a flow system using a three-channel manifold, the peak height being
      proportional to the chloroxine concentration over the range 5.6 x 10(-7)-5.6 x
      10(-5) mol l-1. Manual and flow-injection procedures permit the determination of
      chloroxine in the presence of chlorquinaldol, and have been successfully applied
      to the determination of chloroxine in pharmaceutical preparations.

PMID- 8877857
TI  - Primary structure of bovine adenosine deaminase.
AB  - Derivatized bovine adenosine deaminase is used in enzyme replacement therapy and
      as an adjunct to gene therapy against severe combined immunodeficiency syndrome.
      Although a gene sequence is known for human adenosine deaminase, the structure of
      the bovine enzyme has not been characterized. Structure studies using mass
      spectrometry are reported here that evaluate sequence, processing, post
      translational modifications and the extent of homology between the human protein
      and its therapeutic surrogate.

PMID- 8877858
TI  - Gas chromatography-mass spectrometry identification of a novel N3-methylated
      metabolite of 5'-deoxy-5-fluorouridine in plasma of cancer patients undergoing
      chemotherapy.
AB  - Evidence of in vivo biomethylation of the anticancer pro-drug 5'-deoxy-5
      fluorouridine (5'-dFUR) is presented for the first time. Biomethylation seems to
      occur specifically at the N3 site on the pyrimidine ring. This novel metabolic
      product was detected by gas chromatography-mass spectrometry of the
      trimethylsilylated extract of plasma samples from cancer patients undergoing
      doxifluridine chemotherapy. Considering the observed electron impact
      fragmentation pattern, the metabolic product was tentatively identified as N3-Me
      5'-dFUR. Definite confirmation of the proposed structure was achieved by
      comparison of the mass spectra and chromatographic characteristics of the
      suspected metabolite with those of a synthetically prepared reference standard.

PMID- 8877859
TI  - Determination of droperidol in plasma by liquid chromatography.
AB  - A reversed-phase high performance liquid chromatographic method is described for
      the determination of droperidol concentrations in plasma. Following extraction,
      separation of droperidol and the internal standard flurazepam was achieved with a
      Spherisorb Nitrile, 5 microns, S5CN 250 mm x 4.6 mm column at 200 nm. The mobile
      phase was phosphate buffer (0.05 M, pH 2.4), acetonitrile and ethanol (65:20:15,
      v/v/v). The assay was rapid, sensitive and linear over the range 2-4000 ng ml-1.
      Precision of the assay expressed as the intra- and inter-day relative standard
      deviations (%RSD) did not exceed 10%. Flunitrazepam, midazolam and nitrazepam
      were also resolved with this technique and did not interfere with droperidol or
      flurazepam. Resolution of all five compounds was complete in less than 6 min. The
      assay was used to study the pharmacokinetics of high dose droperidol infusions
      during and after cardiac surgery.

PMID- 8877860
TI  - A sensitive assay for the aminoimidazole-containing drug GP531 in plasma using
      liquid chromatography with amperometric electrochemical detection: a new class of
      electroactive compounds.
AB  - Aminoimidazole-containing compounds have been found to be electroactive and can
      be detected by amperometric electrochemical detection (ECD) with a high degree of
      sensitivity. A liquid chromatography (LC) method using ECD was developed for
      measuring plasma concentrations of the aminoimidazole-containing drug GP531, a
      potent adenosine-regulating agent. Plasma samples were extracted with 2-propanol
      and analyzed by LC under isocratic conditions using a mobile phase of methanol
      sodium phosphate (pH 6.3; 3.3 mM) (32:68, v/v). The potential of the glassy
      carbon working electrode was set at +800 mV. The limit of quantitation was 12.5
      ng ml-1 of GP531 using 100 microliters of plasma. The method was used to define
      the pharmacokinetics of GP531 in monkey following i.v. administration.

PMID- 8877861
TI  - Comparison of liquid chromatography, capillary electrophoresis and super-critical
      fluid chromatography in the determination of Losartan Potassium drug substance in
      Cozaar tablets.
AB  - Reversed phase liquid chromatography, micellar electrokinetic chromatography, and
      packed column supercritical fluid chromatography were used to measure the amount
      of Losartan Potassium drug substance in pharmaceutical tablets. Tablet extract
      samples were analyzed and results were used to compare accuracy, precision, and
      linearity of calibration of the instrumental techniques. All three techniques
      have satisfactory precision (less than 1% RSD) and accuracy to be used for the
      analysis of the drug substance in tablets and the advantages of each technique
      are discussed.

PMID- 8877862
TI  - Development and validation of a capillary zone electrophoretic method for the
      determination of atenolol in presence of its related substances in bulk and
      tablet dosage form.
AB  - The development of a capillary zone electrophoresis method for determination of
      the drug atenolol in the presence of its related substances in bulk and in a
      tablet dosage form is described. The method was fully validated in terms of
      repeatability (RSDs for migration time and peak area of atenolol at 0.05 mg ml-1
      were 0.25% and 0.52%, n = 10, respectively), reproducibility (RSD of peak area
      0.84%, n = 5), linearity at two ranges of atenolol concentration, limits of
      detection and quantitation, ruggedness and robustness. The method was applied to
      the determination of the drug in a commercial tablet preparation (recovery 99.4%,
      m/m). The method proved to be fast and reliable for the quantitative analysis of
      atenolol in the presence of its related substances in bulk and pharmaceutical
      forms.

PMID- 8877863
TI  - Characterization and quantitation of the active polynucleotide fraction (PDRN)
      from human placenta, a tissue repair stimulating agent.
AB  - The polydeoxyribonucleotide (PDRN) fraction is an extract which forms the active
      component in a new formulation of the drug Placentex (a tissue repair stimulating
      agent), obtained from human placenta through an original proprietory extraction
      method. From a comparison of the UV, NMR and IR spectra of this fraction (before
      and after nuclease treatment) with that of a similar standard (Sigma D1501), it
      was shown that the active substances in the PDRN fraction mainly consist of a
      mixture of DNA fragments. By gel electrophoresis, the molecular weights of the
      DNA fragments were shown to range from 50 to 2000 base pairs. Finally, an HPLC
      method is described, based on an anion-exchange material capable of determining
      the amount of PDRN in different batches of the extract, which varied from 80 to
      90%.

PMID- 8877864
TI  - Characterization of metabolites of clozapine N-oxide in the rat by micro-column
      high performance liquid chromatography/mass spectrometry with electrospray
      interface.
AB  - The metabolism of clozapine N-oxide was investigated in the rat (n = 6) after a
      single oral dose of 20 mg kg-1. The organic extracts of rat urine were separated
      by conventional high performance liquid chromatography (HPLC) and individual
      collected fractions were analyzed by micro-column electrospray HPLC/mass
      spectroscopy. The compounds identified in rat urine were clozapine N-oxide,
      clozapine, N-desmethylclozapine, 8-deschloro-8-hydroxyclozapine, 8-deschloro-8
      thiomethylclozapine, N-desmethylclozapine, 8-deschloro-8-hydroxyclozapine, 8
      deschloro-8-thiomethylclozapine, N-desmethyl-8-deschloro-8-thiomethylclozapine
      and 8-deschloro-8-methylsulfinylclozapine. With the exception of the unchanged
      clozapine N-oxide, no other metabolite containing a N-oxide functional group
      could be found, the concentrations of clozapine N-oxide, clozapine and N
      desmethylclozapine excreted from rat urine were determined utilizing a
      conventional HPLC procedure with UV detection. The recoveries of these three
      analytes reported as the percentage of the dosage from the 0.24 h urine are 0.93
      +/- 0.54%, 0.06 +/- 0.03% and 0.01 +/- 0.006% respectively.

PMID- 8877865
TI  - Separation of carnitine enantiomers as the 9-anthroylnitrile derivatives and high
      performance liquid chromatographic analysis on an ovomucoid-conjugated column.
AB  - 9-Anthroylnitrile was used as an achiral reagent for the derivatization of
      carnitine. The reagent forms UV-absorbing derivatives with the hydroxyl groups of
      carnitine enantiomers under very mild conditions. The derivatives were separated
      by high-performance liquid chromatography on an ovomucoid-conjugated column with
      a mobile phase of acetonitrile-20 mM KH2PO4 (adjusted to pH 4.5 with phosphoric
      acid) (17:83, v/v). The separation factor (alpha) and resolution (Rs) of the
      enantiomers were 1.44 and 5.05, respectively. The calibration plots indicated
      good linearity over a sample concentration ranging from 0.2 to 1.0 mg ml-1, and
      the detection limit at 254 nm was 0.05 mg ml-1 for each carnitine enantiomer. The
      reproducibility in the analysis of 1 mg ml-1 of each enantiomer was within 2.0%.
      The method was applied successfully to the determination of carnitine enantiomers
      in pharmaceutical preparations.

PMID- 8877866
TI  - Analysis of the glucuronidation of 7-hydroxycoumarin by HPLC.
AB  - The in-vitro metabolism of 7-hydroxycoumarin to 7-hydroxycoumarin-glucuronide was
      investigated in bovine liver homogenate. A metabolic reaction mixture was
      prepared that included a crude preparation of uridine diphosphate (UDP)
      glucuronyl transferase, 7-hydroxycoumarin and UDP-glucuronic acid. A HPLC method
      was developed to separate coumarin, 7-hydroxycoumarin, 7-hydroxycoumarin
      glucuronide and an internal standard, 4-hydroxycoumarin. Samples were separated
      by reverse-phase HPLC, on a C18 column, with a 1 ml min-1 gradient elution with
      UV detection at 320 nm. The limit of quantification of the method, for 7
      hydroxycoumarin-glucuronide, was 1.47 microM, and the linear range was from 0
      295.7 microM. Concentrations of 7-hydroxycoumarin-glucuronide produced were
      calculated from a plot of 7-hydroxycoumarin-glucuronide concentration versus the
      mean absorbance ratio (n = 4) (7-hydroxycoumarin-glucuronide absorbance/4
      hydroxycoumarin absorbance). It was possible to monitor the decrease in the 7
      hydroxycoumarin content as it was metabolised as well as the increase in 7
      hydroxycoumarin-glucuronide as it was produced enzymatically. The identity of the
      compound produced was confirmed by photodiode array spectral analysis. A plot of
      time versus 7-hydroxycoumarin-glucuronide produced indicates that the metabolism
      is linear for the first 90 min and reached a plateau at 150 min. The rate of
      reaction in the first 90 min was 2.96 +/- 0.06 (RSD 1.7%, n = 3) nmol of 7
      hydroxycoumarin-glucuronide produced per minute per milligram of protein. After
      150 min 0.34 +/- 0.005 mM (RSD 1.4%) 7-hydroxycoumarin-glucuronide was produced,
      from 0.77 mM 7-hydroxycoumarin introduced into the reaction mixture and 58.0% +/-
      5.3% (or 0.44 +/- 0.02 mM) of the 7-hydroxycoumarin remained. These results show
      that it is possible to monitor the production of the phase II metabolite of
      coumarin with minimal sample clean-up and without the need for deconjugation of
      the glucuronide moiety. The method was very reliable and applicable for the
      direct determination of 7-hydroxycoumarin-glucuronide in an in-vitro metabolic
      assay.

PMID- 8877867
TI  - Development of chiral high performance liquid chromatographic assays for the
      enantiomers of 8-hydroxy-(di-n-propylamino)tetralin and three 8-keto-pyrrole
      substituted analogues.
AB  - Two chiral HPLC methods using protein-based stationary phases for the analysis of
      8-hydroxy-(di-n-propylamino)tetralin and three 8-keto-pyrrole analogues are
      presented. Efficient solid-phase extraction enabled quantification of 0.02
      microgram ml-1 of the 8-keto-pyrrole analogues from 500 microliters rat
      hepatocyte suspensions, and 0.2 microgram ml-1 to be measured from 50 microliters
      of rat plasma using UV detection at 315 nm.

PMID- 8877868
TI  - An automated sample preparation and high performance liquid chromatographic
      method for the determination of MK-591, a novel leukotriene biosynthesis
      inhibitor, in human plasma.
AB  - A high performance liquid chromatography assay utilizing an automated sample
      preparation procedure for the determination of a novel leukotriene biosynthesis
      inhibitor, (MK-591), in human plasma has been developed. After aliquoting plasma
      samples and adding internal standard manually, the BenchMate Workstation executed
      protein precipitation and solid-phase extraction. Following evaporation to
      dryness, the residue was reconstituted and chromatographed isocratically on a
      cyano-phase analytical column. MK-591 and the internal standard were separated
      from each other and from endogenous plasma substances and detected with an
      absorbance detector. The assay has been validated in the concentration range 10
      1000 ng ml-1 and has the sensitivity and specificity necessary to quantify plasma
      concentrations from several clinical studies.

PMID- 8877869
TI  - High performance liquid chromatographic determination of phenoxetol, methyl
      paraben, ethyl paraben, n-propyl paraben, iso-butyl paraben, n-butyl paraben and
      croconazole.HCl.
AB  - A high performance liquid chromatographic technique has been used to determine
      phenoxetol, methyl paraben, ethyl paraben, n-propyl paraben, iso-butyl paraben, n
      butyl paraben and croconazole.HCl. The method developed involves isocratic,
      reversed phase chromatography. The range of quantitation was found to be 90-135.0
      micrograms ml-1 for phenoxetol, 2.0-30.0 micrograms ml-1 for methyl paraben, 0.5
      7.5 micrograms ml-1 for ethyl paraben, 0.3-4.5 micrograms ml-1 for n-propyl
      paraben, 0.3-4.5 micrograms ml-1 for iso-butyl paraben, 0.5-7.5 micrograms ml-1
      for n-butyl paraben and 20.0-300 micrograms ml-1 for croconazole.HCl. Linear
      regression analysis of the data demonstrates the adequate performance of the
      method in terms of precision and accuracy.

PMID- 8877870
TI  - Detection and determination of the hydrazo and azo photoproducts of 4
      aminobenzoic acid by high-performance liquid chromatography.
AB  - The photochemistry of 4-aminobenzoic acid has been investigated using two
      validated reversed-phase HPLC methods. Up to nine photoproducts have been
      detected, with chromatographic evidence for the formation of 4,4'
      azobenzenedicarboxylic acid and 4,4'-hydrazobenzenedicarboxylic acid. The
      synthesis and analytical characterization of 4,4'-hydrazobenzenedicarboxylic acid
      is reported.

PMID- 8877871
TI  - Selective spectrophotometric method for the determination of erythromycin and its
      esters in pharmaceutical formulations using gentiana violet.
AB  - A simple and selective method for the determination of erythromycin and its
      stearate and succinate esters in their pure forms and in pharmaceutical
      formulations is described. The procedure is based on the formation of a blue
      coloured (lambda max = 633 nm) complex with gentiana violet in alkaline medium.
      Different variables affecting the colour development were studied and optimized.
      The method was used to determine 2.5-25 micrograms ml-1 of erythromycin in the
      final measured solution. The simplicity of the method permits rapid analysis and
      it is thus suitable for routine control. The method is highly specific for the
      determination of stearate and succinate esters in pharmaceutical formulations.
      The reliability of the method was established by parallel determinations against
      the official British Pharmacopoeial method.

PMID- 8877872
TI  - Resolution of terfenadine enantiomers by reversed phase-high performance liquid
      chromatography using beta-cyclodextrin as mobile phase additive.

PMID- 8877873
TI  - High performance liquid chromatographic determination of prozapine in
      pharmaceutical formulations.

PMID- 8877874
TI  - Photostability-indicating HPLC method for determination of trifluoperazine in
      bulk form and pharmaceutical formulations.

PMID- 8877875
TI  - Simultaneous determination of rifampicin, isoniazid and pyrazinamid by high
      performance thin layer chromatography.

PMID- 8877877
TI  - Physicochemical characterization of a synthetic lipid emulsion for hepatocyte
      selective delivery of lipophilic compounds: application to polyiodinated
      triglycerides as contrast agents for computed tomography.
AB  - A synthetic lipid emulsion (LE) has been developed with physicochemical
      properties that closely resemble those of a specific class of naturally-occurring
      lipoproteins known as chylomicron remnants. The formulation has the potential to
      serve as a hepatocyte-selective delivery system for any lipophilic or amphipathic
      compounds that can be associated with the internal lipid phase of the emulsion.
      In the present studies, a lipophilic polyiodinated triglyceride (ITG) was
      successfully incorporated into the delivery vehicle to form a stable chylomicron
      remnant-like emulsion capable of localizing material to the liver following
      intravenous injection. The preferred ITG-LE formulation was shown to have a mean
      particle diameter of less than 200 nm and a particle size stability profile in
      excess of 12 months. The viscosity, pH, and osmolality of the formulation also
      appeared favorable for safe and convenient intravenous injection. The particle
      size profile, chemical properties, and high degree of incorporation of ITG into
      the emulsion suggest that the ITG-LE formulation holds substantial promise as a
      hepatocyte-selective imaging agent for computed tomography of the liver.
      Biodistribution, elimination, and computed tomography (CT) imaging results in
      animals corroborated the hepatocyte-selective nature of the ITG-LE formulation.

PMID- 8877876
TI  - Plasma direct injection high-performance liquid chromatographic method for
      simultaneously determining E3810 enantiomers and their metabolites by using
      flavoprotein-conjugated column.
AB  - A high-performance liquid chromatographic method using the column-switching
      technique was developed for the simultaneous determination of E3810 and its
      metabolites (M1-M4). An avidin column was used for in-line pretreatment to
      exclude plasma proteins, allowing direct injection of a large volume of plasma. A
      flavoprotein-conjugated chiral stationary phase in a gradient elution mode then
      gave baseline separation of E3810 and the four metabolites. The enantiomers of
      E3810 and M3 were also separated. The method is simple, rapid, accurate, and
      precise. Since no extraction procedure is employed, which might involve different
      recoveries of different metabolites, no internal standard is necessary. The
      method was applied to analyze E3810 and its metabolites in plasma after
      intravenous injection of the drug in beagle dogs.

PMID- 8877878
TI  - Controlled-release delivery system for the alpha-MSH analog melanotan-I using
      poloxamer 407.
AB  - The overall objective of these studies was to develop a controlled-release
      formulation of Melanotan-I (MT-I) containing poloxamer 407 (P407). Various
      aqueous formulations were evaluated containing MT-I and 25% w/v P407 alone, or
      with one of the following additives present, i.e., poly(vinylpyrrolidone) 10000
      (PVP), methylcellulose (MC), or hydroxypropyl methylcellulose (HPMC). The in
      vitro release profiles of MT-I from the P407 formulations and the dissolution of
      the gel were obtained simultaneously using a membraneless in-vitro model. These
      data were obtained at 37 degrees C and room temperature (24 degrees C). It was
      observed that the PVP-containing P407 formulations of MT-I accelerated the
      dissolution of gel and the release of the peptide compared to the control
      formulation. The formulations containing MC or HPMC exhibited the slowest
      dissolution rates and release of MT-I. The same rank order was observed for the
      dissolution and release profiles of MT-I from the various formulations at both
      temperatures. The in-vivo release kinetics of selected formulations were analyzed
      in guinea pigs following intraperitoneal administration. The plasma concentration
      time profiles showed an extended release of the peptide formulated with gel
      compared to the intraperitoneal administration of MT-I in solution. On the basis
      of the in-vitro and in-vivo results, the P407 formulations of MT-I with MC or
      HPMC as an additive showed potential for use as a controlled-release delivery
      system for MT-I.

PMID- 8877879
TI  - In vitro evaluation of a series of N-dodecanoyl-L-amino acid methyl esters as
      dermal penetration enhancers.
AB  - A series of N-dodecanoyl-L-amino acid methyl esters (1-10) and n-pentyl N
      acetylprolinate (11) were evaluated for dermal enhancement properties using an in
      vitro diffusion cell technique. Methods of synthesis of these compounds were
      described. Enhancers were applied 1 h prior to drug treatment. Hydrocortisone was
      used as the model drug and was applied to excised hairless mouse skin as a
      saturated suspension in propylene glycol. Enhancement ratios (ER) were determined
      for permeability coefficient, 24 h diffusion cell receptor concentration (Q24),
      and 24 h full-thickness skin steroid content. Controls received no enhancer
      pretreatment of the skin. N-Dodecanoyl-L-proline (10) showed the highest Q24
      value for total steroid (ER 13.7) while N-dodecanoyl-L-phenylalanine (5) showed
      the highest total steroid skin retention (ER 16.5).

PMID- 8877880
TI  - Study of morphology of reactive dissolution interface using fractal geometry.
AB  - The determination of reactive fractal dimension was carried out using two forms
      of the Noyes-Whitney equation, -dQ/dt = K(Q/Q0)DR/3 and -dQ/dt = K'RDR-3 using
      the Richardson plot on the basis of previous data obtained by dissolution of an
      orthoboric acid powder. The correlation of the results provided by the two ways
      of calculation allows proposal of the hypothesis that dissolution begins on a
      specific population of reactive sites and probably promotes the formation of
      microporous volumes or cracks.

PMID- 8877881
TI  - Topochemistry of the initial stages of the dissolution of single crystals of
      acetaminophen.
AB  - Topochemistry of the initial stages of dissolution of monoclinic single crystals
      of acetaminophen was studied. Etching pits were identified with the sites of
      emerging dislocations. Etching of different faces with a solution of ethyl
      acetate in carbon tetrachloride gave different shapes of etching pits. An
      interpretation of this result was suggested, based on the analysis of the
      anisotropy of the crystal structure. Etching of the same crystal face with
      different etching agents was shown to result in different shapes of etching pits.

PMID- 8877882
TI  - Inhibitors of P-glycoprotein-mediated daunomycin transport in rat liver
      canalicular membrane vesicles.
AB  - P-glycoprotein (P-gp), the multidrug resistance (MDR) gene product, is
      exclusively located on the canalicular membrane of hepatocytes. Recent studies
      using isolated rat canalicular liver plasma membrane (cLPM) vesicles indicate
      that daunomycin (DNM) is a substrate for the ATP-dependent P-gp efflux system in
      the rat liver. The isoforms of P-gp present in cLPM and in cancer cell lines
      differ in that the major form present in the liver represents the gene product of
      mdr2 in mice (MDR3 in humans; class III) while the isoform of P-gp in cancer
      cells is the gene product of mdr1 in mice (MDR1 in humans, class I). The
      objective of this study was to examine the inhibitory effects of various organic
      compounds, most of which have been studied previously in MDR cancer cells, on P
      gp-mediated [3H]DNM uptake into cLPM. Also, the stereospecificity of P-gp for its
      substrates was investigated by comparing the inhibitory effects of the
      enantiomers and the racemic mixtures of verapamil and propranolol. DNM exhibited
      ATP-dependent active transport into rat liver cLPM with a Km of 26.8 +/- 13.4
      microM and a Vmax of 4.9 +/- 0.8 nmol/45 s/mg of protein (n = 4). ADP, AMP, and a
      nonhydrolyzable ATP analogue did not increase DNM transport over the control
      value. Thirty-one potential inhibitors were examined; only acridine orange,
      doxorubicin, verapamil, propranolol, phosphatidylcholine, beta-estradiol
      glucuronide, and DNM itself showed statistically significant inhibition of
      [3H]DNM uptake into cLPM. These results suggest that only a limited number of
      substrates bind to or are transported across the hepatic canalicular membrane via
      P-gp. Phosphatidylcholine, a substrate for the gene product of the class III P-gp
      gene, produced significant inhibition of [3H]DNM transport (30.6% at a 10-fold
      higher substrate concentration), suggesting that transport may be mediated, at
      least in part, by this P-gp gene product. There were no statistically significant
      differences in the inhibitory effects of the enantiomers and racemate of
      verapamil on [3H]DNM transport into cLPM, but the enantiomers of propranolol
      exhibited stereospecific inhibition of DNM transport. (R)-(+)-Propranolol
      produced a statistically significant inhibition of [3H]DNM transport similar to
      that observed with the racemic mixture, while (S)(-)-propranolol showed no
      inhibition. These findings suggest that bile canalicular P-gp may exhibit
      stereospecificity of binding or transport for its substrates.

PMID- 8877883
TI  - In situ ocular absorption of tilisolol through ocular membranes in albino
      rabbits.
AB  - The purpose of this study is to characterize the in situ absorption properties of
      ocular membranes using a cylindrical cell. Drug disappearance in the cell was
      determined as in situ absorption after an application of drug solution into the
      cell on the comea, sclera (bulbar conjunctiva and sclera layer), or palpebral
      conjunctiva. Tilisolol was used as a model of an ophthalmic beta-blocker.
      Tilisolol disappeared from the conjunctival and scleral surfaces although hardly
      any disappearance of tilisolol from the corneal surface was observed. Depletion
      of drug from the precorneal space was much faster in situ than extrapolated from
      permeability measurements (in vitro) of the separate tissues. This may arise from
      an influence of blood flow. The in situ apparent permeability coefficient of
      tilisolol through the conjunctiva was almost constant at various concentrations
      of drug (5-100 mM), suggesting a passive diffusion of tilisolol that was affected
      by medium pH. A high concentration of tilisolol in the aqueous humor was observed
      in the corneal application although the scleral and conjunctival applications
      showed a slight concentration of tilisolol. The corneal route was a dominant
      route of access to the aqueous humor. Access to the vitreous body for tilisolol
      was 4 times more effective through the sclera than through the cornea. On the
      other hand, the corneal application showed an extremely low concentration of
      tilisolol in plasma compared to the scleral and conjunctival applications. Thus,
      the in situ method using a cylindrical cell is a useful method for investigation
      of the ocular absorption of ophthalmic drugs.

PMID- 8877884
TI  - Cells involved in the capture of nanoparticles in hematopoietic organs.
AB  - The affinity of nanoparticles for hematopoietic organs could be valuable for the
      targeting of certain stimulating factors to those tissues, but this affinity
      should also be taken into account in the toxicological evaluation of those
      carriers, especially when they are loaded with antimitotic compounds such as
      doxorubicin. However, the cells responsible for the capture of the nanoparticles
      and their localization in these organs is an important point to know before
      trying to modulate the nanoparticle's tissue distribution. Thus, we have studied,
      in this paper, the capture, the localization, and the retention in the bone
      marrow and in the spleen of biodegradable poly(isohexyl cyanoacrylate)
      nanoparticles as well as of nonbiodegradable polystyrene nanoparticles. The
      histological localization of these nanoparticles has been completed by
      cytological localization with a method used in cytochemistry for the evaluation
      of intracellular accumulation of various substances, such as iron deposits in
      bone marrow sideroblasts. These data indicate that, in the bone marrow, after a
      quick passage through the endothelium, nanoparticles were dispersed throughout in
      the tissue and captured by all types of phagocytizing cells. In the spleen,
      nanoparticles were mainly localized in large angular capturing cells in the
      marginal zone of the lymphoid follicles.

PMID- 8877885
TI  - Effect of nicotinamide and urea on the solubility of riboflavin in various
      solvents.
AB  - Hydrotropy is a solubilization process whereby addition of large amounts of a
      second solute results in an increase in the aqueous solubility of another solute.
      Past investigations have focused on the potential interaction of the hydrotropic
      agent with the solubilized solute. Conversely, this study proposes that at least
      some hydrotropic agents exert their solubilizing effect predominately by
      interacting with the solvent. To that end, the effect of two hydrotropic agents,
      nicotinamide and urea, on riboflavin solubility in aqueous and nonaqueous systems
      was examined. The term "solutropy" is introduced to describe solubilization by
      addition of large amounts of a second solute in any solvent. The nonaqueous
      solvents used included methanol, N-methylformamide, dimethyl sulfoxide, and
      acetone. In water, methanol, and N-methylformamide, riboflavin solubility was
      found to increase with increasing nicotinamide concentration; however, riboflavin
      solubility decreased with increasing nicotinamide concentration in dimethyl
      sulfoxide and acetone, thus establishing the solvent-dependent nature of
      solutropy. An examination of solvent properties revealed that the solvent's
      ability to be both a proton donor and acceptor is important mechanistically,
      while dielectric constant and polarity are not. The same solvent-dependency was
      observed with urea, although urea is a poorer solutrope than nicotinamide. This
      study proposes that some solutropic agents act by changing the nature of the
      solvent, specifically by altering the solvent's ability to participate in
      structure formation via intermolecular hydrogen bonding.

PMID- 8877886
TI  - Development of a two-site immunoassay of recombinant urate oxidase (SR 29142) and
      its use for determination of pharmacokinetic parameters in rats and baboons.
AB  - Two monoclonal antibodies (Mabs), 12C7 and 11G11, both directed against
      recombinant urate oxidase (SR 29142), were selected for their epitope specificity
      to develop a two-site immunoassay of urate oxidase in plasma. A quantitative
      recovery of urate oxidase in plasma was obtained at all the concentrations
      tested, and the limit of quantification was found to be 0.5 ng/mL. Intra-and
      interassay coefficients of variation ranged from 1.2 to 6.7% and from 3.5 to
      10.8%, respectively. The specificity of the two antibodies was studied in Western
      blot experiments. This assay was used successfully to determine urate oxidase
      pharmacokinetic parameters after intravenous injection in rats and baboons. In
      these two species, urate oxidase pharmacokinetics was characterized by a low
      clearance and a low volume of distribution without gender difference.

PMID- 8877887
TI  - Efficient delivery to the lungs of flunisolide aerosol from a new portable hand
      held multidose nebulizer.
AB  - In order to provide asthmatic patients with an inhaler that does not use
      chlorofluorocarbon propellants, a novel multidose hand-held nebulizer (RESPIMAT,
      Boehringer Ingelheim Ltd.) has been developed. This device delivers 200 x 15
      microL metered doses of drug solution, but does not use propellants of any kind.
      In this study of 10 healthy volunteers, the deposition pattern in the lungs and
      oropharynx of an ethanolic solution of flunisolide delivered via a prototype III
      multidose nebulizer has been determined by gamma scintigraphy. A comparison was
      made with the same dose (250 micrograms) of flunisolide delivered by a
      pressurized metered dose inhaler (MDI) and MDI plus Inhacort spacer. Mean (SD)
      whole lung deposition from the multidose nebulizer (39.7 (9.9) % of the metered
      dose) was significantly higher than that from either MDI (15.3 (5.1) %, P < 0.01)
      or MDI plus spacer (28.0 (7.0) %, P = 0.01). A mean 10.4% of the dose was
      recovered from an exhaled air filter for the multidose nebulizer, but less than
      2% of the dose for MDI or MDI plus spacer. Oropharyngeal deposition was
      significantly reduced for the multidose nebulizer (39.9 (9.4) %) compared to MDI
      (66.9 (7.1) %), but was reduced further for the MDI plus spacer (27.3 (11.3) %).
      The multidose nebulizer delivers an unusually high percentage of an aerosol dose
      to the lungs, and it "targets" flunisolide to the lungs more effectively than the
      MDI. The multidose nebulizer could constitute a viable alternative to MDIs in
      asthma maintenance therapy.

PMID- 8877889
TI  - Fractal analysis of sodium cholate particles.
AB  - A fractal analysis was carried out on the powder particles of two samples of
      sodium cholate. A commercial sample had very irregular particles agglomerated,
      and accordingly the fractal dimension of the surface was 2.98, suggesting a
      noteworthy roughness of the particle surface; scanning electron microscopy showed
      that this was due to irregularities caused by a disordered agglomeration of very
      small particles, resulting in larger particles showing polygonal and smooth but
      limited facets. A second sample was obtained by recrystallization from ethanol of
      the commercial sodium cholate and contained large and regular particles, with
      very smooth surfaces. The fractal dimension therefore was accordingly low.
      Despite these differences, the two samples had similar, high reactive dimension
      values to dissolution (2.96 and 2.76, respectively), suggesting that the
      surfactant behavior of sodium cholate is an important parameter in driving the
      dissolution of the solid particles and leveling the surface defects.

PMID- 8877888
TI  - Maternal-fetal pharmacokinetics of zidovudine in rats.
AB  - The disposition of zidovudine (AZT) was investigated in near-term (day 20)
      pregnant rats after intravenous bolus administration of AZT at 50 mg/kg. A
      compartmental pharmacokinetic model was developed to describe AZT concentrations
      in maternal plasma (1), placenta (2), fetus (3), amniotic fluid (4), and the
      maternal tissue compartment (5). Model equations were fitted simultaneously to
      all concentration data by NONLIN least-squares regression. The model that best
      described the AZT concentration data (F test, AIC, sum of weighted squared
      residuals) incorporated bidirectional transfer between maternal plasma reversible
      placenta, placenta reversible fetus, placenta reversible amniotic fluid, and
      maternal plasma reversible tissue compartment. Transfer rate constants (1/h) were
      as follows: k12, 0.58 +/- 0.41; k21, 47.64 +/- 46.61; k23, 67.50 +/- 42.03; k32,
      13.09 +/- 8.80; k24, 0.62 +/- 0.03; k42, 0.32 +/- 0.06; k15, 5.75 +/- 7.00; k51,
      4.12 +/- 1.01; and k10, 1.51 +/- 0.80. AZT rapidly distributed into tissue and
      placenta compartments. However, AZT accumulated more slowly into amniotic fluid.
      Intercompartmental distributional clearances suggest that the mechanism of
      maternal-placental, placental-fetal, and fetal-amniotic fluid transfer of AZT was
      by passive diffusion. This maternal-fetal model for AZT may offer a useful
      approach for describing the placental transfer kinetics of other antiviral
      nucleosides as well.

PMID- 8877890
TI  - Degradation kinetics and isomerization of cefdinir, a new oral cephalosporin, in
      aqueous solution. 1.
AB  - Hydrolytic degradation products of cefdinir were studied in acidic (pH 1),
      neutral (pH 6), and basic (pH 9) solutions. Seven major degradation products were
      isolated by preparative and/or high-performance liquid chromatography and
      characterized by UV, IR, 1H-NMR, and mass spectra. To clarify degradation
      pathways in each pH solution, kinetic and product analyses during hydrolysis of
      cefdinir were carried out along with the followup reaction of representative
      degradation products. Cefdinir was shown to degrade via two major degradation
      routes: beta-lactam ring-opening and pH-dependent isomerizations (lactonization,
      epimerization at C-6 or C-7, syn-anti isomerization of N-oxime function).

PMID- 8877892
TI  - Correlations between n-octanol/water partition coefficients and RP-HPLC capacity
      factors of 1,2-dithiole-3-thiones and 1,2-dithiol-3-ones.
AB  - From the experimental n-octanol/water partition coefficients (log Poct) of 33 1,2
      dithiole-3-thiones and 18 1,2-dithiol-3-ones and their respective log k,
      Collander-type relationships were established at various volume fractions of
      methanol in the mobile phase and on an ODS 2 stationary phase. Collander-type
      relationships were also established between log Poct and log K0 (capacity factor
      extrapolated to 0% of organic modifier). The correlations are good, and their
      parameters depend on the volume fraction of organic modifier, as expected. These
      relationships were used to evaluate the log Poct of seven very lipophilic
      dithiolethiones (3.7 < log P < 7.2). Extrapolated values were compared with
      calculated values from fragmental constants determined in a previous work and
      with those given by Rekker.

PMID- 8877891
TI  - Degradation kinetics and isomerization of cefdinir, a new oral cephalosporin, in
      aqueous solution. 2. Hydrolytic degradation pathway and mechanism for beta-lactam
      ring opened lactones.
AB  - Hydrolysis of cefdinir leads to pH-dependent isomerizations and beta-lactam ring
      opening. Lactam ring opened gamma-lactones were produced as a mixture of four
      diastereoisomers based on the lactone methyl, and C-6 isomerizations in acidic to
      neutral solutions. Cefdinir and its 7-epimer were hydrolyzed to clarify the
      pathway leading to these lactones and the mechanism of C-6 epimerization with the
      aid of chiral separation techniques. Chiral separation using a bovine serum
      albumin column was employed to detect the beta-lactam ring opened products of
      cefdinir and its 7-epimer; the C-6 and C-7 isomerization was thereby observed;
      however, it was found to be pH-dependent at pH > or = 9. Optical activity
      detection applied to the lactones produced from cefdinir and its 7-epimer
      demonstrated that the corresponding peaks of these lactones were enantiomeric
      pairs. In addition, the smallest rate constant at pH 4 was observed for C-6
      epimerization of the lactones, and it was found to proceed without deprotonation
      at C-6 by 1H-NMR spectroscopy. From the results of these studies, a plausible
      mechanism for C-6 epimerization has been proposed. Additionally, it was confirmed
      that two degradation pathways were involved during hydrolysis of cefdinir to the
      lactone.

PMID- 8877893
TI  - Anticonvulsant pharmacodynamics and disposition of triazolam in rats.
AB  - Triazolam (TZ) is a triazolobenzodiazepine used in the treatment of insomnia that
      possesses significant anticonvulsant properties. Despite the widespread use of
      this drug, detailed pharmacokinetic-pharmacodynamic information is lacking,
      especially with respect to inhibition of seizure activity. TZ disposition has
      been described previously by methods with limited specificity, and the
      concentration-anticonvulsant effect relationship has not been characterized. The
      current studies were undertaken to examine TZ disposition with a specific HPLC
      method, and to evaluate the relationship between anticonvulsant effect and
      concentration in Sprague-Dawley rats. TZ pharmacokinetics were characterized
      after bolus or infusion administration; in a separate experiment, TZ
      pharmacodynamics were assessed with pentylenetetrazol-induced seizures. The
      systemic disposition of TZ could be described with a two-compartment model;
      systemic clearance ranged from 2.45 to 5.30 L/h/ kg, steady-state volume of
      distribution ranged from 2.10 to 4.02 L/kg, and mean residence time ranged from
      47 to 65 min. The concentration-effect relationship was well described by a
      simple Emax model: Emax, expressed as the ratio of post-TZ to pre-TZ threshold
      convulsant doses of pentylenetetrazol, was 9.9 +/- 0.7, and the EC50 values were
      10.0 +/- 4.6 ng/mL and 34.8 +/- 9.0 ng/g in serum and whole brain tissue,
      respectively. Under single-dose conditions, TZ is a very potent anticonvulsant in
      the rat pentylenetetrazol seizure model.

PMID- 8877894
TI  - Drug dissolution into micellar solutions: development of a convective diffusion
      model and comparison to the film equilibrium model with application to surfactant
      facilitated dissolution of carbamazepine.
AB  - The intrinsic dissolution rate of carbamazepine in solutions of sodium lauryl
      sulfate was measured to study the convective diffusion transport of drug-loaded
      micelles from a rotating disk. Alternative definitions for effective diffusivity
      and reaction factor are presented and compared with those commonly used for this
      type of transport problem. The conventional and alternative approaches are based
      on the same fundamental assumptions differing only in their interpretation of the
      diffusional boundary layer. For example, in this study it was observed that,
      above the cmc, a 2% w/v solution of sodium lauryl sulfate increased the
      dissolution rate approximately 6-fold and the solubility approximately 20-fold.
      This difference between the solubility and dissolution enhancement was attributed
      to the contribution to the total transport of both the enhanced solubility, a 20
      fold increase, and the effective diffusivity of the drug-micelle complex, a 3
      fold decrease, hence a net 6-fold increase in dissolution. The diffusivity of the
      drug-loaded micelle estimated from the dissolution data using the new definitions
      compared well with values determined by other methods (Dsm = 8.4 x 10(-7) cm2/s).
      On the basis of these results, the new definitions for the effective diffusivity
      and reaction factor offer a practical method for estimating micellar diffusion
      coefficients and predicting drug dissolution under the well-defined hydrodynamics
      of the rotating disk. It may also be possible to extend the application of these
      definitions to study the dissolution of water-insoluble drugs in other media,
      such as emulsions, to better understand drug dissolution under fed conditions in
      vivo.

PMID- 8877895
TI  - Effect of dietary fat content on oral bioavailability of menatetrenone in humans.
AB  - The purpose of this investigation was to determine the effects of fat content and
      frequency of meals on the oral bioavailability of menatetrenone (2-methyl-3-all
      trans-tetraprenyl-1,4-naphthoquinone), a vitamin K2 with four isoprene units. In
      the first series of studies, menatetrenone (15 mg) was administered at breakfast
      time to 18 healthy male volunteers after meals with three different fat contents
      (meals A, B, and C) on three occasions in a crossover design. The three types of
      meals had almost the same calorie content (721-746 kcal) with varied fat contents
      (A, 8.8 g; B, 20.0 g; C, 34.9 g). The area under the plasma menatetrenone
      concentration-time curve within the first 24 h (AUC0-24) increased with increase
      of fat content: 371 +/- 194, 485 +/- 150, and 1024 +/- 341 ng.h/mL (mean +/- SD,
      n = 18) after meals A, B, and C, respectively. On the fourth occasion, the same
      dose of menatetrenone was administered to all volunteers after taking meal B, but
      in this case the lunch 5 h after drug administration was omitted from the
      protocol. The time profile of plasma menatetrenone showed a single peak when
      lunch was not taken, whereas it showed two peaks with lunch. On the fifth
      occasion, 12 out of 18 volunteers took the same dose of menatetrenone after a
      meal with the highest fat content (53.8 g of fat and 789 kcal; meal D), showing
      that AUC0-24 was almost the same as that for meal C, 1027 +/- 389 and 991 +/- 392
      ng.h/mL (n = 12) for meals C and D, respectively. The oral bioavailability of
      lipid-soluble vitamin K was influenced by the fat content of a meal, although the
      increase in bioavailability seemed to reach a peak when the lipid content of the
      meal was > 35 g.

PMID- 8877896
TI  - Role of selected peptides in the vagal regulation of gastric motor and endocrine
      pancreatic function.
AB  - The dorsal vagal complex (DVC) and nucleus raphe obscurus (nROb) are currently
      known to control vagal outflow to the stomach and the pancreas. Elucidation of
      neurotransmitters in these nuclei that control vagal outflow has become necessary
      to determine the endogenous circuitry for control of gastric motor activity and
      pancreatic hormone secretion. In this review, the author's data on the effects of
      selected peptides on intragastric pressure and gastric contractility as well as
      on pancreatic glucagon and insulin secretion in the DVC and nROb are presented.
      Microinjection of thyrotropin-releasing hormone (TRH) or pituitary adenylate
      cyclase-activating polypeptide (PACAP38) into the nROb results in gastric
      excitatory motor responses, whereas substance P (SP) and vasoactive intestinal
      polypeptide (VIP) evoke gastric relaxation. Irrespective of colocalization of TRH
      and SP in the serotonergic neurons of the nROb, these peptides independently
      affect gastric motor function when microinjected into the nROb. The inhibitory
      effect of SP on gastric motor function in the nROb is apparently mediated via
      nitric oxide in the DVC and involves peripheral VIP, acetylcholine, gamma
      aminobutyric acid and nitric oxide. Microinjection of endothelin, PACAP38, and
      VIP into the DVC evokes increases in gastric motor activity. Pancreatic
      polypeptide, microinjected into the DVC, does not affect basal plasma insulin and
      glucagon concentration but potentiates glucose-stimulated insulin secretion. All
      these data make an important contribution to our understanding of the vagal
      mechanisms controlling gastric motor and endocrine pancreatic function.

PMID- 8877897
TI  - The source of contracticle calcium in guinea-pig cardiac myocytes treated with
      thapsigargin.
AB  - We investigated the source of activator Ca2+ in the cells deprived of
      sarcoplasmic reticulum (SR) Ca2+ by pretreatment with 10(-6) mM thapsigargin
      (TG). These cells show Ca2+ transients of nearly normal amplitude, albeit with
      the slowed kinetics. We found in the voltage clamped and loaded with Indo 1-AM
      cells that at depolarizing potentials from -30 to +70mV, blocking of sarcolemmal
      Ca2+ channels with 20 microM nifedipine or 20 microM Cd2+ reduced Ca2+ transients
      and contractions as much in the cells treated with TG as in the normal cells. The
      residual Ca2+ transients were mostly subthreshold for the contractile system. The
      result suggests that in the cells treated with TG, Ca2+ influx by the reversed
      Na/Ca exchange is not more important for activation of contraction than in the
      normal cells. In the normal cells shortening of one of the depolarizing pulses (+
      5mV) applied at a steady rate of 30/min from 200 ms to 5, 10, 20, 30, 50, or 100
      ms little affected amplitude of the respective Ca2+ transients, although their
      duration was decreased proportionally to the decrease of the duration of the
      pulse. In the cells pretreated with TG, 20 ms pulses initiated Ca2+ transients
      which were hardly visible in the records of fluorescence. Their amplitude
      increased with increase in the duration of the pulses linearly correlating with
      the charge transfered with the Ca2+ current. We propose that the direct source of
      Ca2+ activating contraction in the guinea-pig ventricular myocytes is sarcolemmal
      Ca2+ influx mostly through the sarcolemmal Ca2+ channels. The alternative
      hypothesis is that there is some yet unidentified cellular source of activator
      Ca2+ (internal leaflet of sarcolemma?) from which it may be released by
      sarcolemmal Ca2+ influx.

PMID- 8877898
TI  - The effects of male gender and female sex hormone deficiency on the vascular
      responses of the rat in vitro.
AB  - Male gender and menopause increase the risk for cardiovascular incidents by
      mechanisms that have not yet been fully clarified. Recent evidence suggests that
      the cardioprotective property of female sex hormones may be partly related to
      direct vasodilation. Accordingly, we examined the possible differences in
      arterial reactivity in vitro between normal female, ovariectomized female and
      normal male rats. Endothelium intact mesenteric artery rings were used to
      determine concentration response curves for noradrenaline, potassium chloride,
      acetylcholine and sodium nitroprusside. When compared to normal female rats, the
      maximal contractions to noradrenaline and potassium chloride were increased both
      in the ovariectomized female and in male rats. The relaxation induced by sodium
      nitroprusside was enhanced both in normal and ovariectomized females when
      compared to the male rats. There were no differences in relaxation responses to
      acetylcholine between normal or ovariectomized female or male rats. In
      conclusion, male gender and ovarian hormone deficiency increase arterial
      reactivity to constricting factors and reduce the vasodilatory effects of
      endothelium-independent relaxing agents.

PMID- 8877899
TI  - Effects of heat shock and teprenone on ethanol-induced damage to cultured rabbit
      gastric mucosal cells.
AB  - We examined whether or not heat shock and teprenone (a gastric mucosal protective
      drug), through the induction of heat shock proteins (HSPs), protect cultured
      rabbit gastric mucosal cells from ethanol-induced damage. Cell viability was
      assessed by mitochondrial function and membrane permeability assays. Exposure of
      mucosal cells to 5% ethanol for 1h caused an about 50% reduction in viability.
      When the cells had been heated at 43 degrees C for 1 h, the cell damage caused by
      ethanol was significantly prevented. However, pretreatment with teprenone at 1
      100 microM failed to prevent the ethanol-induced damage. Western blot analysis
      with an anti-HSP-72 antibody showed that HSP-72 was apparently induced by heat
      treatment, but not by teprenone. Both the cytoprotection and induction of HSP-72
      on heat treatment were potently inhibited by cycloheximide and actinomycin D.
      These results demonstrate that, in rabbit gastric mucosal cells, the induction of
      HSPs is strongly associated with cytoprotection against ethanol-induced damage,
      but that teprenone has no effect on the cytoprotection or HSP induction.

PMID- 8877900
TI  - Subserosal application of transforming growth factor-beta 1 in rats with chronic
      gastric ulcers: effect on gastric ulcer healing and blood flow.
AB  - Transforming growth factor beta 1 (TGF-beta 1) has been shown to play a central
      role in wound healing. This peptide has been detected in the stomach, but no
      information is available at present whether TGF-beta 1 influences the healing of
      gastric ulcers and whether the mucosal expression of TGF-beta 1 changes in the
      course of this healing. In this study, gastric ulcers were induced by serosal
      application of acetic acid and TGF-beta 1 or vehicle saline was injected twice
      into the subserosa around the ulcer area, once immediately after ulcer induction
      and two days later. Local application of TGF-beta 1 led to significant
      acceleration of gastric ulcer healing. Gastric blood flow at the ulcer margin was
      significantly higher than that in the ulcer crater but no significant difference
      was found in this flow between studied groups. Immunohistochemistry showed that
      the expression of TGF-beta 1 reached the peak at day 2 and then declined in the
      course of healing. We conclude that TGF-beta 1 accelerates ulcer healing possibly
      by increasing the formation of granulation tissue and cell migration probably
      mediated by locally expressed TGF-beta 1 but the healing effects of TGF-beta 1 do
      not depend on the vascular factor.

PMID- 8877901
TI  - Adaptation of pancreas to repeated caerulein-induced pancreatitis in rats.
AB  - Induction by caerulein of acute pancreatitis with tissue damage and acinar cells
      loss is followed by recovery. We studied biochemical, histological and functional
      regeneration of pancreatic tissue after repeated acute pancreatitis. Pancreatitis
      was evoked in rats by s.c. infusion of caerulein (10 micrograms/kg/h) for 5 h.
      After infusion, rats were divided into three groups. First group was infused with
      caerulein one time, in the second group infusion of caerulein was repeated 10
      days later. The third groups was infused with caerulein for the 3rd time 10 days
      after the 2nd infusion. Rats were sacrificed at time sequence of 0, 12, 24, 48,
      72 hours and at 5th, and 10th day after last infusion of caerulein. Pancreatic
      blood flow (PBF) was measured using laser Doppler flowmeter. Plasma and
      pancreatic amylase, pancreatic weight, RNA and DNA contents, and histological
      changes were determined. We found that DNA and RNA content, as well, as
      histological changes in 1st group showed progressive regeneration after 3 days.
      Regeneration after 1st time caerulein-induced pancreatitis was almost completed
      within 10 days and amylase content in the tissue and plasma amylase level
      returned to normal values. Each subsequent infusion of caerulein caused
      significantly less pronounced destruction of the pancreatic tissue, however, the
      regeneration occurred progressively later than after the 1st or 2nd infusion.
      Tissue repair after the 2nd infusion reached peak at 5th day while after 3rd
      infusion at 10th day. PBF dropped after 1st caerulein induced pancreatitis by
      about 50% but with repeated caerulein induced pancreatitis lower decreases in PBF
      were observed and they returned in shorter time back to control value. These
      results indicate that the pancreas is able to adapt to repeated injury and this
      is manifested by cumulative decrease of pancreatic damage after each repetition
      of induction of acute pancreatitis and correlated with the preservation of PBF,
      however, the pancreatic tissue regeneration is significantly delayed.

PMID- 8877902
TI  - Dysfunction in gastric myoelectric and motor activity in Helicobacter pylori
      positive gastritis patients with non-ulcer dyspesia.
AB  - Helicobacter pylori (Hp) infection has been shown to affect gastric acid
      secretion and the somatostatin-gastrin ratio but its effects on gastric motility
      have not been evaluated. This study was carried out in 12 patients (10 males and
      2 females, mean age 33 +/- 6 yrs) who underwent endoscopy and Campylobacter-like
      Organism (CLO)-test. All patients were found initially to be Hp positive
      according to CLO-test. Gastric emptying was evaluated by measuring antral
      diameter with ultrasonography (Hitachi EUB 240) in fasted and fed patients.
      Electrogastrography (EGG) with antral manometry were done 5 h before and 4 h
      after a meal before the therapy and one month after the eradication with triple
      therapy (lanzoprazole 30 mg daily- 2 x 250 mg clarithromycin 500 mg t.i.d.-3 x
      500 mg and metronidazole 500 mg b.i.d.-2 x 500 mg). In Hp positive patients
      before the triple therapy the mean fasted antral diameter was 4.3 cm2, initial
      EGG showed significant dysrhythmia of electrical control activity (ECA) with
      tachygastria up to 25% of recording time in 9 of 12 Hp positive patients without
      normal increase of the power of signal in any of tested subjects. In 7 Hp
      positive fasted antral manometry failed to exhibit gastric phases III of the
      migrating motor complex (MMC). Hp eradication was accomplished in 10 of 12
      examined patients and this was followed by a decrease in tachygastria to 3 cpm
      rhythm with an increase of the ECA power after meal. Phase III of MMC was
      observed again in 7 Hp negative patients with a decrease of fasted antral
      diameter (p < 0.05). Fasted and fed antral motility pattern increased after
      eradication. Two patients remained Hp positive after standard therapy. We
      conclude that most symptomatic non ulcer dyspeptic Hp positive patients show
      changes in ECA and antral hypomotility that are associated with Hp infections.

PMID- 8877903
TI  - Role of dopamine in the secretory function of corpus luteum in cattle.
AB  - To investigate the role of dopamine (DA) in the secretion of progesterone and
      ovarian oxytocin (OT) in cattle in vivo and in vitro studies were performed.
      Luteal slices (middle stage of the luteal phase) were incubated-with five
      different amounts of DA (10(-3)-10(-7) M) and after 1, 2 and 4 h medium was
      collected for the progesterone and OT determination. The only 10(-5) M of DA
      enhanced OT medium concentrations (P < 0.05-0.001) and this response increased
      within duration of the incubation. The same dose of DA affected (P < 0.05-0.001)
      progesterone release during the incubation period. Next we wanted to study
      whether this mechanism will operate in conscious cattle. Mature heifers had
      cannulae inserted into the aorta abdominalis through the coccygeal artery for
      local infusion of saline or drugs, and into the jugular vein and the cava vena
      caudalis for the blood sample collection. In Experiment 2 six heifers on days 10
      12 of the cycle received in Latin square design DA (8.4 micrograms/kg/min) for
      2h, and they were pre-treated for 2 h with saline or for 1 h with droperidol
      (DROP; 1 microgram/kg/min) or with 4 micrograms/kg/min of beta-blocker,
      propranolol (PROP). DA increased (P < 0.05) OT plasma concentrations in all
      groups but secretion of progesterone was not changed (P > 0.05). DA decreased
      prolactin concentrations if pre-infused with saline and PROP and DROP diminished
      this effect of DA. Data suggest that DA affected OT release from both pituitary
      and from the ovary. Hence in Experiment 3 we wanted to elucidate whether DA
      caused those effects itself of after its conversion to the noradrenaline (NA). DA
      was given in six heifers as in Experiment 2 and blood samples were taken
      simultaneously from the vena cava and from the jugular vein. Within a few minutes
      from the start of DA infusion, large amount of DOPAC was measured by HPLC in
      blood. Next NA increase (P < 0.01) was observed in both veins but it was always
      higher (P < 0.05) in the vena cava. However, OT concentration in blood samples
      from both veins was not different (P > 0.05). Data indicate that DA can stimulate
      the secretory function of CL in cyclic heifers supposedly after its conversion to
      NA.

PMID- 8877904
TI  - The role of prostaglandins and the hypothalamic and hippocampal histamine in the
      clonidine-induced pituitary-adrenocortical response.
AB  - Involvement of prostaglandins (PGs) and histamine in the hypothalamus and
      hippocampus in the clonidine-induced pituitary-adrenocortical response was
      investigated in conscious rats. The hypothalamic-pituitary adrenocortical (HPA)
      activity was assessed indirectly by measuring corticosterone secretion.
      Clonidine, an alpha 2-adrenergic agonist, given intracerebroventricularly (10
      micrograms icv), considerably increased the serum corticosterone and hypothalamic
      histamine levels and markedly elevated the hippocampal histamine levels. Systemic
      or icv pretreatment with indomethacin (2 mg/kg or 10 micrograms), an inhibitor of
      prostaglandin synthesis, significantly reduced the clonidine-induced
      corticosterone response and abolished the increase in the hypothalamic and
      hippocampal histamine levels elicited by clonidine. Indomethacin in the doses
      used did not substantially change the resting serum corticosterone or
      hypothalamic and hippocampal histamine levels. These results indicate that
      prostaglandins and hypothalamic histamine are considerably involved in the HPA
      response to alpha 2-adrenergic receptor stimulation. They also suggest
      involvement of prostaglandins and histamine of the hippocampus in the clonidine
      induced HPA response.

PMID- 8877905
TI  - Effects of calcium channel antagonists on the reinforcing properties of morphine,
      ethanol and cocaine as measured by place conditioning.
AB  - Morphine, ethanol and cocaine were examined in place conditioning paradigm. After
      initial preferences were determined, animals were conditioned with morphine (5
      mg/kg), ethanol (1 g/kg) and cocaine (5 mg/kg) alone or combinations of these
      drugs plus some calcium antagonists: nifedipine (5 and 10 mg/kg) and verapamil (5
      and 10 mg/kg). Nifedipine prevented the ability of morphine and cocaine, but not
      of ethanol, to produce a place preference. Our results suggest that substances
      which can influence calcium distribution are involved in the rewarding actions of
      some drugs-morphine and cocaine. Dihydropyridine, a calcium channel antagonists
      might be clinically useful for the treatment of morphine and cocaine abuse.

PMID- 8877906
TI  - Influence of thyroid hormones on exercise tolerance and lactate threshold in
      rats.
AB  - Effects of thyroid hormone deficit, and triiodothyronine (T3) treatment on
      exercise performance, blood lactate (LA) concentrations and LA threshold (TLA)
      were studied in trained and untrained rats. Fourteen rats were thyroidectomized
      and then treated with propylthiouracil for 30 days (THY + PTU group). Fourteen
      sham operated rats served as controls. In each group there were 7 sedentary and 7
      endurance-trained animals. Six weeks after thyroidectomy or sham operation the
      rats were subjected to a multistage running test with speed increasing from 13
      m/min at 10 degrees treadmill inclination till maximum. Blood samples for LA were
      taken from the rats' tail after each 3-min exercise stage. During 3 days
      following this test rats from all groups were injected (i.p.) with 75
      micrograms/100 g of triiodothyronine (T3), and 24 hrs afterwards the second
      exercise test was performed. In THY + PTU rats maximal running speed (RSmax) and
      the speed at which TLA occurred were markedly decreased in comparison with
      control group. The level of LA at the maximal speed (LAmax) and that
      corresponding to TLA were higher in THY + PTU rats than in controls. T3 injection
      to control animals diminished their RSmax and TLA, whereas in THY + PTU rats it
      increased RSmax and shifted TLA to a higher speed. Both in THY + PTU and control
      animals T3 elevated LAmax and the threshold LA concentration. Endurance training
      in control and THY + PTU animals markedly enhanced RSmax and TLA. This was
      accompanied by increases in LAmax and concentration of LA at TLA only in control
      group. After T3 injection to control trained rats RSmax and TLA were diminished,
      whereas in THY + PTU trained group RSmax was unchanged and TLA was elevated.
      Maximal blood LA increased only in THY + PTU trained rats whilst the threshold
      blood LA was elevated in both groups. It is concluded, that both the T3
      deficiency and its excess reduce maximal exercise performance and shift TLA to
      lower workloads. Enduarance training or administration of T3 to hypothyroid rats
      markedly improve their exercise performance and elevate TLA, however, T3
      treatment markedly increases maximal and submaximal LA levels.

PMID- 8877907
TI  - Human acclimation to work in warm and humid environments.
AB  - The aim of this study was to analyse the acclimation of male Europeans during a
      forty-one day stay in the hot and humid climate of Thailand. We also tried to
      examine the phases of acclimation which would eventually be used by trainers in
      the elaboration of the schedule of athletes' preparation to participate in
      competitions in a tropical climate. Twelve Polish male subjects ageing 21-38
      years participated in these examinations. In Poland and Thailand the
      cycloergometric exercise test with the load of 53% of VO2max was performed until
      a 1.2 degrees C (delta Tre) increase in rectal temperature was reached. The
      exercise test was executed in the same environmental conditions (i.e. 30 +/- 1
      degrees C and 70 +/- 3% of relative humidity). The duration of this exercise test
      (DE) was used as a criterion for the efficiency of thermoregulatory functions.
      During acclimation, three peaks of greater exercise thermoregulatory efficiency
      have been found, i.e. on the 4th-5th, 11th-12th and 29th-30th days of stay. These
      findings are particularly important for professional athletes who wish to prepare
      themselves for competitions held in hot and humid climates.

PMID- 8877908
TI  - Competitive and non-competitive NMDA receptor antagonists induce c-Fos expression
      in the rat anterior, cingulate cortex.
AB  - In the present study we tried to find out whether the competitive NMDA receptor
      antagonist CGP 40116 was capable of inducing c-Fos expression in the rat
      cingulate cortex in a manner similar to that described previously for the non
      competitive NMDA receptor antagonist MK-801. Induction of fast early genes by MK
      801, especially in the rat cortex, has recently been linked with the neurotoxic
      effects of non-competitive NMDA receptor antagonists on cortical neurones, hence
      it was of interest to extend those studies to another class of NMDA receptors
      antagonists i.e., competitive one. It was found that CGP 40116 (2.5 and 5 mg/kg)
      induced c-Fos expression in the rat anterior cingulate cortex. That effect was
      dose-dependent and was shown as an increase in the number of cells expressing the
      c-Fos immunoreactivity. A qualitatively similar, but quantitatively stronger,
      effect was observed after administration of MK-801 (0.2 and 0.4 mg/kg), which
      also caused a dose-dependent increase in the number of c-Fos positive neurones.
      The described dose-dependent effects of CGP 40116 and MK-801 are shown as an
      increase in the number of c-Fos-positive neurones, but not as an increase in the
      optical density of c-Fos immunostaining in c-Fos positive neurones. In control,
      vehicle-injected rats, the constitutive c-Fos immunoreactivity was not found in
      the rat anterior cingulate cortex. The obtained data indicate that both
      competitive and non-competitive NMDA receptor antagonists may induce similar
      effects on the c-Fos immunoreactivity in the rat anterior cingulate cortex, and
      that their administration may lead to similar functional consequences resulting
      form activation of fast, early genes.

PMID- 8877909
TI  - Effect of vitamin E on peroxidation and permeability of the peritoneum.
AB  - Because of the evidence that peritoneal macrophages are activated during
      peritoneal dialysis, we hypothesised that the injury of the peritoneum is, at
      least in part, dependent on the intraperitoneal generation of free radicals. The
      aim of the study was to evaluate the effect of vitamin E on the peroxidation and
      permeability of the peritoneum during chronic peritoneal dialysis in rats.
      Supplementation of the intraperitoneally infused saline with vitamin E decreased
      the peroxidation of peritoneum estimated as the malondialdehyde (MDA) level in
      rats' omentum. However the permeability of the peritoneum to glucose and protein
      in vitamin E treated rats was increased. In in vitro study we have found that
      vitamin E is cytotoxic to human mesothelial cells (HMC) as measured by inhibition
      of their proliferation and this effect was irreversible. We conclude that vitamin
      E, despite its antioxidant effect, causes the changes of the peritoneum
      permeability which could decrease the effectiveness of peritoneal dialysis.

PMID- 8877910
TI  - New approach to 13C-urea breath test: capsule-based modification with low-dose of
      13C-urea in the diagnosis of Helicobacter pylori infection.
AB  - This study was designed to evaluate a novel modification of the non-invasive
      capsule-based 13C-urea breath test (13C-UBT). 114 patients were tested for
      Helicobacter pylori (HP) infection with the use of only 38 mg 13C-urea
      administrated in solid capsulated form. Obtained results were compared with
      tissue based methods: histology and rapid urease test (CLOtest). Results of
      histology and/or CLOtest were considered as the gold standard for each patient.
      In addition, also capsule-based, micro-dose (37kBq) 14C-urea breath test (14C
      UBT) was performed. With a cut-off for delta-over-base values of 5/1000 (i.e., 5
      per mil), 13C-UBT results (measured by non-dispersive infrared spectroscopy,
      NDIRS) correlated highly significant with combined results for invasive methods
      i.e., CLOtest + histology score. Compared with histology, CLOtest, and the gold
      standard, the diagnostic values of the test were: sensitivity 97%, specificity
      95%, with positive and negative predictive values about 90% and 98% respectively.
      The modified 13C-UBT test was found to be in full concordance with 14C-UBT; there
      was 100% agreement in the diagnostic classification of all positive (89) and
      negative (25) patients. Described modification of 13C-UBT showed that presented
      modification of 13C-UBT is an excellent, simple, low cost, non invasive, and safe
      diagnostic tool in HP detection and should be recommended particularly in cases
      when the use of radioactive urea is contraindicated.

PMID- 8877911
TI  - The future of rheumatology: new directions?

PMID- 8877912
TI  - The future of rheumatology: paradigm shift or turf war?

PMID- 8877913
TI  - Development and progression of osteoarthritis.

PMID- 8877914
TI  - The importance of community based epidemiological studies.

PMID- 8877915
TI  - Where's the evidence? Putting clinical science into pediatric rheumatology.

PMID- 8877916
TI  - Thrombin in the synovial fluid of patients with rheumatoid arthritis mediates
      proliferation of synovial fibroblast-like cells by induction of platelet derived
      growth factor.
AB  - OBJECTIVE: To investigate the clotting and fibrinolytic activities in synovial
      fluid (SF) from patients with rheumatoid arthritis (RA) and to examine the role
      of thrombin in synovial hyperplasia. METHODS: We measured the amounts of thrombin
      antithrombin-III complex (TAT), antithrombin-III (AT-III), thrombin, plasminogen,
      alpha 2-plasmin inhibitor (alpha 2-PI), and plasmin-alpha 2-antiplasmin complex
      (PAP) in SF of 20 patients with RA and 16 patients with osteoarthritis (OA). The
      proliferative response of synovial fibroblast-like cells to thrombin was measured
      using [3H] thymidine incorporation. Expression of platelet derived growth factors
      (PDGF) in conditioned medium was analyzed using a Western blot method, and
      expression of the mRNA of PDGF and their receptors was analyzed by reverse
      transcription polymerase chain reaction. RESULTS: The amounts of clotting factors
      (TAT, AT-III) and fibrinolytic factors (plasminogen, alpha 2-PI, and PAP) were
      significantly higher in the patients with RA than in patients with OA (p < 0.01).
      Moreover, SF thrombin concentrations of patients with RA correlated significantly
      with erythrocyte sedimentation rates (rs = 0.751, p < 0.01) and serum C-reactive
      protein concentrations (rs = 0.531, p < 0.05). Thrombin exhibits mitogenic
      activity toward synovial fibroblast-like cells in vitro, and this mitogenic
      activity is associated with an increase in the expression of mRNA of both PDGF
      alpha receptor and PDGF-beta-receptor. CONCLUSION: The high levels of thrombin
      activity in the SF of patients with RA and strong mitogenic activity of thrombin
      toward the synovial fibroblast-like cells suggest that thrombin plays an
      important role in the pathogenesis of RA.

PMID- 8877917
TI  - Interleukin 1 (IL-1) receptor antagonist, soluble tumor necrosis factor
      receptors, IL-1 beta, and IL-8--markers of remission in rheumatoid arthritis
      during treatment with methotrexate.
AB  - OBJECTIVE: To examine circulating levels of cytokines and cytokine inhibitors and
      their production by blood mononuclear cells (MNC) in patients with active
      rheumatoid arthritis (RA) before treatment with methotrexate (MTX) and inactive
      disease upon treatment as well as healthy control individuals. METHODS:
      Interleukin-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor
      receptors p55 and p75 (sTNFr; p55 and p75), interleukin-1 beta (IL-1 beta), tumor
      necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and monocyte
      chemoattractant protein 1 (MCP-1) were assessed by immunoassays in sera and MNC
      culture supernatants of 27 patients with RA with active disease before and 14
      patients with inactive disease during MTX treatment, and 10 healthy controls.
      RESULTS: Levels of circulating IL-1ra, sTNFr p55 and p75 were higher in patients
      with active RA compared to those with inactive disease or controls. At the
      cellular level, resting MNC of patients with active RA released more IL-1 beta
      and IL-8, but less IL-1ra, and showed a lower ratio of IL-1ra:IL-1 beta than MNC
      of patients without inflammatory symptoms or healthy controls. In addition,
      unstimulated and in vitro lipopolysaccharide stimulated MNC cultures of patients
      with inactive RA released higher amounts of sTNFr p75 than MNC of patients with
      active RA. CONCLUSION: Circulating levels of IL-1ra and sTNFr as well as IL-1
      beta, IL-8, and sTNFr p75 release from MNC and the ratio of IL-1ra:IL-1 beta
      production by these cells serve as markers to assess complete disease remission
      in patients with RA during MTX treatment.

PMID- 8877918
TI  - Reliability and validity of a submaximal treadmill test to estimate aerobic
      capacity in women with rheumatic disease.
AB  - OBJECTIVE: To assess reliability and validity of a single stage submaximal
      treadmill test to estimate aerobic capacity in women with rheumatic disease.
      METHODS: 30 women with rheumatic disease (rheumatoid arthritis = 19; systemic
      lupus erythematosus = 5; mixed connective tissue disease = 2; psoriatic arthritis
      = 4) performed a submaximal exercise test at a self-selected walking speed
      between 3.2 and 7.2 km/h on 2 occasions, and one subjective maximal exercise test
      with respiratory gas analysis. Estimation of aerobic capacity from the submaximal
      test was obtained from a regression equation using age, walking speed, and
      exercise heart rate. Aerobic capacity from maximal testing was determined by
      observed peak oxygen consumption and by estimation using test duration in a
      regression equation. Correlation and regression analyses were performed to assess
      test-retest reliability and criterion validity of the submaximal method. RESULTS:
      Intraclass correlation coefficient for the submaximal test was ICC = 0.97 (95% CI
      = 0.94-0.99). Comparison of results from the submaximal test to the maximal test
      using both observation and estimation methods to determine aerobic capacity
      ranged from r = 0.77 to 0.80, with R2 of 0.59 to 0.65. The submaximal regression
      model, originally developed and validated in a sample of persons without
      rheumatic disease, was significantly different in this sample of women with
      rheumatic disease. CONCLUSION: This single stage treadmill test, suitable for use
      in clinical and community settings, appears to be a reliable and valid method to
      safely assess aerobic capacity in women with rheumatic disease. There was a
      tendency for the submaximal method to overestimate aerobic capacity in this
      sample.

PMID- 8877919
TI  - Comparison of standard and alternative health assessment questionnaire scoring
      procedures for documenting functional outcomes in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To compare statistical properties of data from the Health Assessment
      Questionnaire (HAQ) with those from an alternative version (AHAQ) that used a
      different scoring system for the item categories and disability index.
      Comparisons included descriptive statistics, correlations, and inferential
      statistics to determine whether the AHAQ would be a more sensitive measure of
      change in functional status. METHODS: The subjects were 107 adults diagnosed with
      rheumatoid arthritis and hospitalized for exacerbations in their arthritis or
      arthritis related joint surgery. Disability was assessed upon admission to
      hospital and at one year followup with the HAQ. AHAQ scores were generated for
      the item categories making up the disability index by taking the mean of the item
      scores in a category instead of the worst item score; the disability index was
      the mean of the alternative category scores. RESULTS: The standard method of
      scoring the HAQ was found to generate greater variance on category scores, lower
      correlations between category scores and the total disability index, and lower
      correlations between first and 2nd administrations of the instrument, compared to
      the AHAQ. HAQ disability index scores also correlated slightly lower than those
      of AHAQ to scores from the HAQ pain scales, and to scores from 2 other measures
      of functional disability. In addition, the AHAQ was found to be more powerful in
      detecting functional changes at one year followup. CONCLUSION: Because of its
      statistical properties the AHAQ scoring method may be preferable to the HAQ
      method when the instrument is used for documenting change in functional outcomes.

PMID- 8877920
TI  - Self-assessment of disease activity by patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the reliability of self-assessment of disease by patients
      with rheumatoid arthritis (RA), with a particular emphasis on the assessment of
      articular swelling. METHODS: A questionnaire was developed using components from
      validated instruments. Information was obtained on global function, global joint
      tenderness/swelling, and joint pain (10 cm visual analog scales), duration of
      musculoskeletal morning stiffness (grade 1-6), ACR functional score (grade 1-4),
      tender joint count (0-20), tender joint score (0-60), swollen joint count (0-20),
      and swollen joint score (0-60). Data were collected prospectively on 61 patients
      with RA in a teaching clinic or office practice by 4 staff rheumatologists.
      Patient questionnaires were completed within 24 h before physician assessments.
      Followup assessments were carried out on 27 patients after a mean interval of 3
      months (range 0.5-6). RESULTS: At the initial assessment there was a significant
      correlation between patient and physician assessments for global function (r =
      0.83; p = 0.01) [intraclass correlation coefficient (ICC) = 0.83; p < 0.01],
      global joint tenderness/swelling (r = 0.83; p < 0.01) (ICC = 0.83; p < 0.01),
      global joint pain (r = 0.83; p < 0.01) (ICC = 0.81; p < 0.01), duration of
      morning stiffness (r = 0.83; p < 0.01) (ICC = 0.85; p < 0.01), ACR functional
      score (r = 0.61; p < 0.01) (ICC = 0.62; p < 0.01), tender joint count (r = 0.57;
      p < 0.01) (ICC = 0.31; p < 0.01), and tender joint score (r = 0.60; p < 0.01)
      (ICC = 0.35; p < 0.01). However, there was poor correlation between patient and
      physician assessments for both swollen joint count (r = 0.16; p > 0.05) (ICC = 
      0.02; p > 0.05) and swollen joint score (r = 0.24; p > 0.05) (ICC = 0.12; p >
      0.05). Longitudinal analysis indicated significant correlation between changes in
      patient and physician assessments in all variables except swollen joint count and
      score. CONCLUSION: Although there was good correlation between most variables for
      patient and physician assessments of disease activity in RA, there were
      substantial differences in the assessment of joint swelling. This objective
      determinant of disease activity cannot be ascertained in self-report measures of
      health status.

PMID- 8877921
TI  - Increase of bone mineral density and anabolic variables in patients with
      rheumatoid arthritis resistant to methotrexate after cyclosporin A therapy.
AB  - OBJECTIVE: To determine the bone mineral density (BMD) and anabolic variables in
      a cohort of patients with severe, early rheumatoid arthritis (RA) resistant to
      weekly doses of methotrexate (MTX), after addition of cyclosporin A (CyA)
      therapy. METHODS: We studied 10 rheumatoid factor positive patients of 58 with
      early erosive, aggressive RA with poor response to a 6 month course of MTX (< 20%
      improvement in the American College of Rheumatology core set of criteria). BMD
      was assessed at entry, after 6 months of MTX, and after a further 6 months of
      combination therapy of MTX plus CyA. Bone Gla protein (BGP)
      dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor-1 (IGF-1,
      somatomedin C) levels were determined along with clinical variables and acute
      phase reactants (C-reactive protein, erythrocyte sedimentation rate). RESULTS: An
      average BMD decline of 4.05 +/- 0.8% (mean, SD) occurred in the first 6 months of
      MTX treatment, along with a statistically significant decline of IGF-1 (-24.8%),
      DHEAS (-21.6%), and BGP (-19.7%) levels. After adding CyA 3 mg/kg daily for 6
      months, BMD had increased by 3.9 +/- 0.97%, IGF-1 by 42.4%, DHEAS by 34.2%, BGP
      by +34.3%. These changes mirrored the clinical variables (Health Assessment
      Questionnaire, morning stiffness, joint count) and acute phase reactants, which
      improved in a statistically significant manner. CONCLUSION: Patients with active
      RA, even in the early phases, lose bone very rapidly. Effective control of
      systemic inflammation allowed a rapid rescue of BMD, at least in the short term.
      This happened with a simultaneous increase in some anabolic variables such as IGF
      1, BGP, and DHEAS.

PMID- 8877922
TI  - Beta 2-glycoprotein I and anticardiolipin antibody binding to resting and
      activated cultured human endothelial cells.
AB  - OBJECTIVE: To examine beta 2-glycoprotein I (beta 2-GPI) binding and its ability
      to augment IgG anticardiolipin (aCL) antibody binding to resting and cytokine
      activated endothelial cells in vitro. To evaluate the ability of IgG aCL antibody
      positive sera to induce endothelial cell activation in vitro. METHODS: IgG with
      aCL activity was isolated by affinity purification from 6 patients with systemic
      lupus erythematosus (SLE) and 3 patients with primary antiphospholipid antibody
      syndrome (APS). Human umbilical vein endothelial cells (HUVEC) were cultured in
      serum-free conditions and examined in a resting state or after activation with
      tumor necrosis factor alpha (TNF-alpha). HUVEC were exposed to beta 2-GPI alone,
      IgG alone or IgG plus beta 2-GPI. Finally, we examined the ability of sera from
      the same patients with SLE and primary APS to activate HUVEC in culture. RESULTS:
      Neither beta 2-GPI, IgG aCL, nor IgG aCL plus beta 2-GPI bound to resting or
      cytokine activated endothelial cells. In addition, sera from the same patients
      did not induce in vitro activation of endothelial cells as assessed by enhanced
      surface expression of intercellular adhesion molecule, vascular cell adhesion
      molecule, and E-selectin. CONCLUSION: Results suggest that beta 2-GPI deposition
      on either resting or activated endothelial cells and modulation of its proposed
      in vivo anticoagulant activity through subsequent aCL antibody binding does not
      account for the thrombotic manifestations of APS.

PMID- 8877923
TI  - The use of methotrexate in polymyalgia rheumatica.
AB  - OBJECTIVE: To examine the efficacy and steroid sparing potential of methotrexate
      (MTX) in the treatment of polymyalgia rheumatica (PMR) without giant cell
      arteritis. METHODS: 43 patients with PMR were treated with MTX 7.5 mg/wk for 3
      months. This dose was raised to 10 and finally 12.5 mg/wk MTX if the desired
      response was not obtained. RESULTS: No patient benefitted clinically or
      statistically from treatment with MTX. CONCLUSION: MTX is of no benefit in the
      treatment of PMR.

PMID- 8877924
TI  - Incidence of osteoperiostitis of the great toe in psoriatic arthritis.
AB  - OBJECTIVE: To assess the incidence of osteoperiostitis of the distal phalanx of
      the great toe in psoriatic arthritis (PsA). METHODS: One thousand great toes (202
      of PsA, 44 of cutaneous psoriasis, 274 of low back pain patients, 296 of
      rheumatoid arthritis, 136 of spondyloarthropathy, and 48 of connective tissue
      diseases) were studied for osteoperiostitis of the distal phalanx of the great
      toe (slight, moderate, or severe), destructive joint lesions of the feet, nail
      dystrophy, fungal infection, and HLA-B type (patients with PsA). RESULTS:
      Osteoperiostitis was observed in 92 great toes. Moderate and severe
      osteoperiostitis were observed only in PsA. Osteoperiostitis was statistically
      more frequent in PsA (53/202, 26.2%, especially in those with onychosis: 20/41,
      48.8%) than in other groups (39/798, 4.9%) (p < 0.01). In PsA, osteoperiostitis
      was more frequent in patients with nail dystrophy (20/41, 48.8%) than in patients
      without (33/161, 20.5%) (p < 0.05). Fungal infection of the nail and HLA
      haplotype were not associated with osteoperiostitis. In patients with PsA,
      osteoperiostitis was associated with destructive joint lesions of the feet.
      CONCLUSION: Osteoperiostitis of the distal phalanx of the great toe is an
      enthesopathy evocative of PsA.

PMID- 8877925
TI  - Dual energy X-ray absorptiometry in patients with lower limb reflex sympathetic
      dystrophy syndrome.
AB  - OBJECTIVE: To assess the difference in bone mineral density (BMD) between
      pathologic and healthy legs in reflex sympathetic dystrophy syndrome (RSDS) using
      a whole body BMD with dual energy X-ray absorptiometry (DEXA). METHODS: Cross
      sectional evaluation of BMD in 55 patients with RSDS compared BMD of the affected
      and the healthy limb with 121 controls. Followup was performed on 21 patients
      treated with intravenous pamidronate. RESULTS: In the cross sectional study, BMD
      was reduced in the dystrophic affected extremities and this reduction correlated
      with the duration of evolution of the disease. In the longitudinal study, BMD
      remained stable in patients treated with pamidronate. CONCLUSION: The cross
      sectional study confirms that DEXA is not a diagnostic tool. The longitudinal
      study confirms DEXA is accurate, nontraumatic, rapid, and safe for longterm
      quantitative assessment of unilateral bone loss caused by lower limb RSDS.

PMID- 8877926
TI  - Five years of clinical experience with intermittent cyclical etidronate for
      postmenopausal osteoporosis.
AB  - OBJECTIVE: To evaluate the effects of 120 weeks of intermittent cyclical
      etidronate on the progression of bone loss and fracture incidence and rate in
      postmenopausal osteoporotic women after 150 weeks of either etidronate or placebo
      treatment. METHODS: This was an open label followup study of 37 postmenopausal
      osteoporotic women enrolled from the earlier 150 week study, 17 from the
      etidronate group and 20 from the placebo group. Treatment cycles were of oral
      doses of etidronate 400 mg/day for 2 weeks, followed by a 13 week drug-free
      period for a total of 120 weeks. All patients received a daily supplement of 0.5
      g calcium and 400 U vitamin D. RESULTS: During the earlier 150 week study, mean
      vertebral bone mineral content increased significantly in the etidronate group by
      5.5% (p = 0.013) and decreased by 2.7% (not significant) in the placebo group.
      After 120 weeks of etidronate treatment in this followup study, patients who had
      formerly received etidronate experienced an additional 1.4% increase; after 5
      years, bone mineral content was 6.9% above the original baseline (p = 0.037).
      Bone mineral content also increased in the former placebo group during the latter
      study, up to 5.3% above the original study baseline (not significant). The
      vertebral fracture rate in the former placebo group decreased significantly, from
      103 to 27 per 100 patient-years (p < 0.01), while the fracture rate in the former
      etidronate group was unchanged (38 and 33 per 100 patient-years). CONCLUSION:
      Five years of etidronate therapy for postmenopausal osteoporosis results in
      significant increases in vertebral bone mineral content, and the previously
      observed reduction in vertebral fracture rate in the etidronate group is
      maintained during at least 5 years of therapy.

PMID- 8877927
TI  - Risk factors for progression to new sites of radiographically defined
      osteoarthritis in women.
AB  - OBJECTIVE: To describe the association between hormonally related risk factors
      and the progression to new sites of radiographically defined full body
      (generalized) osteoarthritis (OA) in a cohort of older women. METHODS: A
      retrospective cohort design was used to study former radium dial painters over
      the age of 40 years who had minimal radium exposure. At study entry and at
      varying followup times, clinical examinations were conducted and full body
      radiographs were taken. Two followup groups were defined: women with a followup
      radiograph 1-9 years after baseline (n = 75) and 10-19 years after baseline (n =
      53). Fifty-five joints (10 joint groups) were independently graded at baseline
      and followup for OA by the method of Kellgren and Lawrence, and provided the
      basis for summary full body OA progression scores. Progression was defined as an
      increase in the number of sites with OA and in separate analyses as an increase
      in the number of joint groups with OA. RESULTS: Increasing length of followup and
      lower baseline OA score were associated with greater OA progression, while age at
      baseline examination showed no clear relation to progression. Beyond these
      variables, increasing height and having ever smoked were inversely associated
      with OA progression, while body mass index (BMI) showed a weak positive
      association. In multivariable modeling for followup 1-9 years, only lower
      baseline OA score predicted greater OA progression to new sites (partial r2 =
      0.13, p = 0.0009). In followup 10-19 years, baseline OA score (partial r2 = 0.12,
      p = 0.0011), height (partial r2 = 0.057, p = 0.033), and smoking status (partial
      r2 = 0.09, p = 0.035) were independent predictors of OA progression to new sites,
      while greater BMI was a positive, weak, and nonsignificant predictor (partial r2
      = 0.031, p = 0.29). History of prior cholecystectomy, hysterectomy, dilation and
      curetage, number of pregnancies, and change in BMI were not significantly related
      to progression of OA to new sites. Similar results were found for predictors of
      OA progression to new joint groups. CONCLUSION: Lower baseline level of OA is
      associated with greater OA progression to new sites or joint groups independent
      of age, suggesting a "burnout" phenomenon. In addition, shorter height and having
      never smoked appear to be independent risk factors that predict the progression
      of radiographic OA to new sites or joint groups.

PMID- 8877928
TI  - Viscosupplementation with hylan for the treatment of osteoarthritis: findings
      from clinical practice in Canada.
AB  - OBJECTIVE: To evaluate viscosupplementation with intraarticular hylan G-F 20 in
      current clinical practice. METHODS: A retrospective study of all patients with
      osteoarthritis of the knee treated with hylan by 5 Canadian clinicians over a
      period of 2.5 years. RESULTS: A total of 1537 injections were performed in 336
      patients involving 458 knees. The overall response and the change of activity
      level were judged better or much better for 77 and 76% of the treated knees after
      the first course of treatment (3 weekly injections), and 87 and 84% after a 2nd
      course. The mean time elapsing between the first and 2nd course, 8.2 +/- 0.5
      months, is an evaluation of the duration of benefits. Local adverse events were
      observed in 28 patients (32 knees), with an overall rate of 2.7% adverse events
      per injection, 7.0% per joint, and 8.3% per patient. No systemic adverse events
      were noted in any patient. The adverse events were characterized by pain and/or
      transient swelling of the injected joint, mostly mild or moderate in intensity,
      and 72% of the adverse events were considered to be possibly or probably related
      to the injection. The incidence of adverse events is significantly influenced by
      the injection technique: 5.2% adverse events per injection with a medial approach
      to a partially bent knee, and 2.4% (straight medial) and 1.5% (straight lateral).
      After an adverse event, clinical improvement still occurred in 69% of the
      affected knees. CONCLUSION: Hylan G-F 20 provided good clinical benefits and an
      acceptable safety profile in current clinical practice. The occurrence of adverse
      events after an intraarticular hylan injection is infrequent and unpredictable
      and is not necessarily hylan related, although injection related.

PMID- 8877929
TI  - Coordinated regulation of hyaluronan and aggrecan content in the articular
      cartilage of immobilized and exercised dogs.
AB  - OBJECTIVE: To study the influence of joint loading and immobilization on
      articular cartilage hyaluronan concentration and histological distribution in the
      knee joints of young dogs subjected to 11 weeks' immobilization by splinting, and
      15 weeks' running exercise at a rate of 40 km/day. METHODS: The amount of
      hyaluronan in articular cartilage was determined by a competitive binding assay
      using a biotinylated hyaluronan binding complex (HABC) of aggrecan and link
      protein. Histologic sections were stained for the localization of hyaluronan with
      the HABC probe. Extracted proteoglycans were characterized by sodium dodecyl
      sulfate agarose gel electrophoresis. RESULTS: Immobilization significantly
      reduced the concentration of hyaluronan in all sites studied (tibial and femoral
      condyles, patellar surface of femur). The proportion of hyaluronan to total
      uronic acid (mainly from aggrecan) remained unchanged because of a concurrent
      decrease in aggrecan. The ratio of hyaluronan and aggrecan remained constant also
      in runners. The staining pattern of free hyaluronan in the tissue sections and
      the electrophoretic mobility of the extracted proteoglycans were not affected by
      the different loading regimes. CONCLUSION: Reduced joint loading due to splint
      immobilization significantly decreases both hyaluronan and aggrecan in the
      articular cartilage. The remarkably parallel changes in aggrecan and hyaluronan
      content suggest that joint loading exerts a coordinated influence on their
      metabolism.

PMID- 8877930
TI  - Hereditary osteoarthritis with mild spondyloepiphyseal dysplasia--are there "hot
      spots" on COL2A1?
AB  - OBJECTIVE: To define the genetic basis of a family with an autosomal, dominantly
      inherited form of spondyloepiphyseal dysplasia (SED) associated with tall
      stature. METHODS: A 6 generation family with early onset osteoarthritis (OA)
      associated with mild SED was studied. 14 individuals were examined clinically and
      radiologically, and DNA analysis was performed on 5. As the clinical pattern of
      joint involvement and tall stature of affected individuals resembled a family
      recently reported with an exon 11 mutation in COL2A1, this same mutation was
      specifically sought. In 2 clinically affected and 3 unaffected family members,
      exon 11 was amplified by polymerase chain reaction (PCR) followed by restriction
      enzyme digestion with Asp H1, the enzyme recognition sequence of which is altered
      by the mutation. The PCR product containing exon 11 was then directly sequenced.
      RESULTS: OA with widespread involvement of peripheral joints, in addition to
      spondylodysplasia, was seen in 14 members of the kindred. Affected family members
      had brachydactyly and were of average to above average height. Asp H1 digestion
      of the PCR product containing exon 11 in those with clinical disease was
      consistent with the presence of a mutation. Direct sequencing of this PCR product
      conclusively showed that a single base substitution was present in those with
      clinical disease, resulting in an arginine 75-cysteine (Arg75-Cys) mutation.
      CONCLUSION: We describe a 3rd family with an Arg75-Cys mutation with precocious
      generalized OA and mild SED. This finding supports the concept of mutational hot
      spots on COL2A1 related to the hypermutability of the cytosine-guanine doublet.

PMID- 8877931
TI  - Determination of stromelysin-1, 72 and 92 kDa type IV collagenase, tissue
      inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in synovial fluid and serum
      from patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the correlation between serum and synovial fluid (SF)
      concentrations of stromelysin-1 (MMP-3), gelatinases (MMP-2 and MMP-9), tissue
      inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in patients with rheumatoid
      arthritis (RA) and to assess the role of these proteins in cartilage destruction
      and their clinical value as indicators of disease activity. METHODS: Enzyme
      linked immunoassays (ELISA) were used. SF and serum samples were collected
      simultaneously from 55 patients with RA. Radiographic (Larsen grade) and clinical
      evaluations were also done. RESULTS: There was significant correlation between SF
      concentrations of MMP-3 and MMP-9. In addition, there was significant negative
      correlation between SF concentrations of TIMP-2 and MMP-2, 3, and 9. The only
      correlation observed among MMP and TIMP in serum was that of MMP-3 with MMP-2.
      Significant correlation was also found between MMP-3 concentrations in the serum
      and SF. There were no significant correlations between radiological grade and
      concentrations of these proteins. Patients with mild to moderate functional
      disability showed significantly higher serum TIMP-1 concentrations than patients
      with severe disability. CONCLUSION: Extremely high concentrations of MMP-3 in SF
      of the patients with RA may contribute to its elevation in serum. It would seem
      that regulation of TIMP production depends upon the disease state and not the
      concentration of MMP. Discrepancies between concentrations of TIMP and MMP in SF
      may be responsible for cartilage destruction in RA.

PMID- 8877932
TI  - A multicenter, randomized, double blind study comparing lornoxicam with
      diclofenac in osteoarthritis.
AB  - OBJECTIVE: To compare the efficacy and tolerability of lornoxicam and diclofenac
      in the treatment of patients with osteoarthritis (OA) over 12 weeks and to assess
      the efficacy and tolerability of lornoxicam over a followup period of 40 weeks.
      METHODS: In a double blind, parallel group study, 135 patients (mean age 63
      years) with OA of the hip and/or knee were randomized to receive lornoxicam 4 mg
      3 times daily (tid), lornoxicam 8 mg twice daily (bid), or diclofenac 50 mg tid
      for 12 weeks. 85 patients who completed this 12 week treatment period
      subsequently received lornoxicam 4 mg tid or 8 mg bid for up to 40 weeks.
      RESULTS: Over the initial 12 week treatment period, intention-to-treat analysis
      revealed improvements in the functional index of severity for OA in all 3 groups
      by -1.5 to -1.9 points and pairwise testing demonstrated significant intergroup
      equivalence (p < 0.033). Confirmatory analysis demonstrated the expected efficacy
      as outlined in the sample size calculation. The percentage of patients showing
      improvements in disease activity (about 46%) and pain intensity (42 to 48%) was
      also similar and a clear majority of patients also reported "some" or "excellent"
      pain relief (80 to 89%). A per protocol analysis produced similar results. During
      the 40 week lornoxicam followup treatment period there was slight deterioration
      in the functional index of severity of OA (0.3 to 1.1 points). This minor change
      may reflect the natural course of the disease rather than a loss of efficacy in
      lornoxicam. Disease activity and pain intensity continued to improve but in a
      lesser proportion of patients (< 23%) compared to the previous phase.
      Nevertheless, a similar high percentage of patients (78 to 89%) reported "some"
      or "excellent" pain relief. Adverse events in both phases of this study were
      consistent with those commonly reported during treatment with nonsteroidal
      antiinflammatory drugs and included headache and gastrointestinal events. There
      was no difference in the frequency or severity of adverse events between any of
      the treatment groups. Lornoxicam was well tolerated in the long term. CONCLUSION:
      Lornoxicam 4 mg tid and 8 mg bid were as effective as diclofenac 50 mg tid for
      the treatment of OA. There was no significant difference in tolerability of these
      regimens. Thus, lornoxicam appears to be a useful therapeutic alternative to
      diclofenac in patients with OA.

PMID- 8877933
TI  - Musculoskeletal complaints and fibromyalgia in patients attending a respiratory
      sleep disorders clinic.
AB  - OBJECTIVE: To determine the frequency of fibromyalgia (FM) syndrome and reporting
      of pain in an unselected group of patients attending a respiratory sleep
      disorders clinic, and to examine the association of physical activity and levels
      of reported pain. METHODS: 108 consecutive patients attending a respiratory sleep
      disorders clinic were interviewed and examined, blind to sleep disorder status.
      Assessment of musculoskeletal pain symptoms included patient history of pain,
      painful sites marked on a mannequin, visual analog scale (VAS) pain score, and
      tender point count. Daily physical activity was recorded, and all patients
      underwent nocturnal polysomnography, blind to clinical status. RESULTS: FM was
      identified in 3 patients (2.7%). Pain reporting was more strongly associated with
      reduced physical activity than with a specific sleep disorder. Patients with
      reduced physical activity were more likely to have pain symptoms than physically
      active patients: tender point count > or = 6 (p = 0.002), > or = 3 sites marked
      on mannequin (p = 0.008), axial pain (p = 0.003), and VAS pain score (p = 0.008).
      CONCLUSION: FM by defined criteria was uncommon in patients with a primary
      complaint of disturbed sleep, and in particular, patients with sleep apnea.
      Reduced physical activity was strongly associated with reported pain symptoms.

PMID- 8877934
TI  - The natural history of chronic pain in the community: a better prognosis than in
      the clinic?
AB  - OBJECTIVE: To evaluate the predictors of improvement at 2 years in subjects with
      chronic widespread pain ascertained from a community survey. METHODS: As part of
      a community based epidemiological survey on the occurrence of pain, 141 subjects
      (age range 24-74 years; 44 men, 97 women) were selected for more detailed
      assessment. Followup information on pain experience was collected at a median of
      27 months (range 15-35). Subjects were categorized according to whether they had
      no pain, chronic widespread pain (according to the American College of
      Rheumatology criteria), or regional pain, both at initial assessment and
      followup. In addition, subjects were examined at both time periods for tender
      points. RESULTS: Of those with chronic widespread pain at initial assessment, 35%
      still had chronic widespread pain at followup, 50% regional pain, and 15% no
      pain. Of those originally with regional pain, 65% still had regional pain, 19%
      chronic widespread pain, and 16% no pain at followup. Logistic regression
      analysis was conducted to examine factors among those with chronic widespread
      pain associated with still having these symptoms at followup. Female sex, older
      age, leaving school at a young age, high tender point count, high levels of
      fatigue, or additional physical or psychological symptoms were all associated
      with symptoms being less likely to resolve. CONCLUSION: Chronic widespread pain
      in the community has a generally good prognosis. However, those with additional
      symptoms associated with the fibromyalgia syndrome were more likely still to have
      chronic widespread pain 2 years later.

PMID- 8877935
TI  - Muscle force, perceived effort, and voluntary activation of the elbow flexors
      assessed with sensitive twitch interpolation in fibromyalgia.
AB  - OBJECTIVE: To measure maximal voluntary strength and central activation without
      fatigue, and to assess both peripheral and central components of muscle fatigue
      of the elbow flexor muscles, during exercise, in a group of patients with
      fibromyalgia (FM) (n = 11). Results are compared with data from control subjects
      (n = 36). METHODS: Maximal voluntary activation and strength of elbow flexors
      were quantified using twitch interpolation during attempted maximal isometric
      contractions both in unfatigued muscles and during fatigue produced by 45 min of
      submaximal exercise. RESULTS: Maximal voluntary strength of the elbow flexors
      before and during exercise was within the normal range. Central fatigue did not
      develop to a greater extent in the patient group. No patient had a decline in
      twitch amplitude during exercise below the 95% confidence limit for the decline
      in control subjects. However, the increment in perceived effort (Borg Scale) was
      abnormally large in 5 patients during the fatiguing exercise. CONCLUSION: Neither
      poor motivation, reflex pain inhibition, nor muscle contractile failure are
      important in the pathogenesis of fatigue in patients with FM. However, the
      subjective response to exercise is commonly excessive.

PMID- 8877936
TI  - Widespread pain: is an improved classification possible?
AB  - OBJECTIVE: The classification of widespread pain, proposed by the American
      College of Rheumatology (ACR) for use in the clinic as a screen for fibromyalgia,
      as described, does not require truly widespread pain. Studies considering the
      epidemiology of widespread pain per se may therefore require a definition with
      greater face validity, which might also show enhanced associations with other
      physical and psychological measures. We aimed to develop a more coherent
      definition of widespread pain for use in epidemiological studies and to compare
      performance in identifying individuals with significant morbidity. METHODS: A
      group of 172 subjects who had participated in a community based study on the
      occurrence of pain were identified and categorized by their pain experience as
      indicated on line drawings of the body according to ACR definition and to a new,
      more stringent definition that required the presence of more diffuse limb pain. A
      number of other clinical and psychological measures were recorded for these
      individuals and the association between their pain status measures and these
      other variables was assessed and compared. RESULTS: Persons satisfying the newly
      proposed definition for chronic widespread pain, in comparison with those who
      satisfied only the present ACR definition, had a significantly higher score on
      the General Health Questionnaire [median difference (MD) 7.95% CI 1.13], a higher
      score on the Health and Fatigue Questionnaire (MD 10.95% CI 0.15), and greater
      problems with sleep (sleep problem score MD 4.95% CI 0.9). Those satisfying the
      new definition also had a greater number of tender points on examination (MD
      3.95% CI -1.7). The morbidity of those satisfying only the present ACR definition
      was closer to persons who had regional pain. CONCLUSION: A redefinition of
      widespread pain has produced a group of subjects whose pain is (a) likely to be
      more "widespread" and (b) is associated more strongly with factors such as
      psychological disturbance, fatigue, sleep problems, and tender points, and may be
      more appropriate in epidemiological studies.

PMID- 8877937
TI  - Extracapillary glomerulonephritis in a patient with juvenile chronic arthritis.
AB  - A patient with juvenile chronic arthritis (JCA) in remission developed the
      nephrotic syndrome 17 years after the onset of the disease. A renal biopsy showed
      diffuse extracapillary proliferative glomerulonephritis without immune complex
      deposits. The patient was treated with glucocortico-steroids and
      cyclophosphamide. Extracapillary glomerulonephritis without immune complex
      deposits appears to be a rare complication of JCA.

PMID- 8877938
TI  - Crescentic glomerulonephritis in juvenile chronic arthritis.
AB  - Juvenile chronic arthritis (JCA) was diagnosed in 2 young girls. In one of them,
      antinuclear antibodies (ANA) were strongly positive during the course of erosive
      polyarthritis. After 5 years followup, severe renal insufficiency occurred.
      Antineutrophil cytoplasmic antibodies (ANCA) were positive with a perinuclear
      pattern on indirect immunofluorescence (IIF) and antimyeloperoxidase (MPO)
      specificity. Renal biopsy showed severe crescentic glomerulonephritis without
      significant deposits on IIF. Treatment consisted of prednisone and monthly
      intravenous cyclophosphamide pulse. Renal failure worsened and hemodialysis was
      necessary. A 2nd patient was referred for polyarthritis with positive rheumatoid
      factors without positive ANA. The presence of microscopic hematuria led to the
      discovery of crescentic glomerulonephritis with positive ANCA of anti-MPO
      specificity. At latest examination, after prednisone for 10 months and
      azathioprine for 6 months, the patient had moderate proteinuria with normal renal
      function. These observations emphasize that in juvenile onset chronic
      polyarthritis, renal microscopic angiitis with ANCA of anti-MPO specificity may
      occur.

PMID- 8877939
TI  - Exacerbation of peripheral neuropathy during alpha-interferon therapy in a
      patient with mixed cryoglobulinemia and hepatitis B virus infection.
AB  - An association between hepatotropic viruses, chiefly hepatitis C virus (HCV),
      occasionally hepatitis B virus (HBV), and mixed cryoglobulinemia has been widely
      reported. Alpha-interferon (IFN-alpha) has usefully been employed in the
      treatment of mixed cryoglobulinemia, particularly for liver and renal
      involvement. IFN-alpha treatment may be associated with neurological
      complications, including peripheral neuropathy. We describe an HBV positive
      patient with mixed cryoglobulinemia with recurrent purpura, mild sensory
      peripheral neuropathy, and active hepatitis treated with IFN-alpha. Rapid
      improvement of the purpura, liver enzymes, and cryocrit, and disappearance of
      serum HBV DNA were observed after a 4 week treatment period. However, concomitant
      worsening of the neuropathy prompted us to discontinue IFN-alpha. Although in
      this case, a positive effect of IFN-alpha on the clinico-serological and
      virological variables was confirmed, due to the possible exacerbation of
      neurological manifestations, a careful patient evaluation is necessary before
      starting IFN-alpha in patients with mixed cryoglobulinemia.

PMID- 8877940
TI  - Polymyositis developing after prolonged injections of pentazocine.
AB  - Pentazocine is a frequently used analgesic drug. Numerous complications have been
      reported in association with its use, including skin fibrosis, skin ulceration,
      abnormal skin pigmentation and symmetrical myopathy. Fibrous myopathy is a rare
      but conspicuous complication of prolonged pentazocine injection. However,
      inflammatory myopathy has not previously been related to this substance abuse. We
      describe a patient who developed polymyositis after 13 months of pentazocine
      injections.

PMID- 8877941
TI  - Calcium pyrophosphate dihydrate deposition disease presenting as tumoral
      calcinosis (periarticular pseudogout).
AB  - It has been considered unusual for periarticular calcifications to consist of
      calcium pyrophosphate dihydrate (CPPD). We describe a patient presenting with
      pain and inflammation adjacent to the site of tumoral calcifications and
      extending to the first metatarsophalangeal joint. Aspiration of the material
      revealed weakly positive birefringent rhomboid shaped crystals that proved to be
      CPPD by atomic force microscopy. The patient had no metabolic abnormalities or
      radiographic chondrocalcinosis. We believe other cases similar to ours represent
      another clinical form of CPPD deposition disease-periarticular pseudogout.

PMID- 8877942
TI  - Treatment of juvenile rheumatoid arthritis: approach to patients who fail
      standard therapy.
AB  - Approaches to the initial management of juvenile rheumatoid arthritis and
      comprehensive therapeutic strategies for the management of children who fail to
      respond to first line treatment are reviewed. Guidelines for introducing advanced
      antirheumatic drugs, combination therapy, experimental agents, and alternative
      forms of therapy are considered.

PMID- 8877943
TI  - What's new in the treatment of pediatric SLE.
AB  - Therapy in pediatric systemic lupus erythematosus (SLE) is reviewed by examining
      the pediatric experience, including uncontrolled retrospective observations and
      case reports. In addition, I extrapolate from the adult experience and interpret
      findings in light of pediatric SLE.

PMID- 8877944
TI  - Henoch-Schonlein purpura: when and how to treat.
AB  - The many facets of Henoch-Schonlein purpura are described with emphasis on the
      gastrointestinal and renal manifestations. The controversy surrounding management
      of children with abdominal pain and nephritis is discussed with a review of the
      current literature to support recommendations for treatment options.

PMID- 8877945
TI  - Treatment of rheumatoid joint inflammation with intrasynovial triamcinolone.

PMID- 8877946
TI  - Lupus cystitis improved with oral prednisolone therapy.

PMID- 8877947
TI  - SAPHO syndrome and spondyloarthropathy.

PMID- 8877948
TI  - Cervical cord compression complicating atlantoaxial subluxation in ankylosing
      spondylitis.

PMID- 8877949
TI  - Are antineutrophil cytoplasmic antibodies of immunodiagnostic value in reactive
      arthritis?

PMID- 8877950
TI  - Results of "satisfaction with disease control" survey.

PMID- 8877951
TI  - Rheumatoid arthritis and disability depicted in a Durer engraving.

PMID- 8877952
TI  - Treatment protocol for fractures of the odontoid process.
AB  - Treatment results in 104 patients with odontoid fractures were reviewed. There
      were 2 type I, 62 type II, 32 type III fractures and eight epiphysiolyses in
      children <7 years old. Thirty-seven patients were managed nonoperatively using
      plaster casts, cervical braces, or halo devices. Sixty-seven patients were
      treated surgically including anterior screw fixation (ASF), posterior fusion
      (PF), and transoral anterior fusion (TAF). Plaster casts and cervical braces were
      effective for type I fractures and epiphysiolyses only. Halo devices provided
      successful results in stable type III fractures. ASF is the treatment of choice
      for most type II and unstable III fractures including some old cases. PF also
      provided successful union, although impaired cervical motion remained. It should
      be reserved for irreducible fractures, established nonunions, and as a salvage
      procedure. TAF should be limited to exceptional cases requiring anterior spinal
      cord decompression.

PMID- 8877953
TI  - Role of posture in mechanics of the lumbar spine in compression.
AB  - Biomechanics of the entire lumbar spine L1-S1 in erect postures was investigated
      under physiological axial compression loads of up to 800 N with and without right
      axial torques of up to 10 Nm using a nonlinear finite-element model. The sagittal
      curvature is varied from an initial value of 46 degrees by +15 degrees to model
      more lordotic posture and by -7.5 degrees as well as -15 degrees to model
      flattened lumbar spines. The primary/coupled displacements, disc pressures,
      ligament forces, facet forces, disc fiber strains, along with the required
      stabilizing sagittal/lateral moments, are computed at different levels, loadings,
      and lordotic postures. The role of facetectomy and partial nucleotomy at some
      levels is also studied for a few cases. The primary/coupled motions, disc
      pressures, facet loads, and disc fiber strains are all affected by postural
      changes and the addition of 10-Nm axial torque. The primary responses are
      stiffened when axial compression and axial torque are applied together rather
      than separately. Flexion and left lateral moments are required to stabilize the
      lumbar spine in compression. The changes in lordosis markedly affect the
      stabilizing sagittal moments. The lateral moments, however, are significantly
      influenced only in the presence of axial torque. Axial compression generates
      small disc fibers that decrease from the innermost layer to outer ones at all
      disc levels. The contact forces are largest at the L5-S1 facets. These forces
      cause large differences in rotation between L5 anterior and posterior bony
      structures, suggesting the high stresses on corresponding pedicles and pars
      interarticularis. Finally, the stabilizing flexion moments are generated
      primarily by the off-centeredness of the gravity load. Relatively small muscle
      forces are required to balance the remaining portion.

PMID- 8877955
TI  - Safety of thoracic transverse process fixation: an anatomical study.
AB  - An anatomical study of the passage of the implant placed around thoracic
      transverse process was undertaken in human cadavers to investigate the safety of
      thoracic transverse process fixation. A simulated surgical procedure for implant
      placement around the transverse processes of T1-T10 was carried out in eight
      fresh human cadavers using a mock plastic implant, 7.0 mm wide and 1.5 mm thick.
      A total of 80 implanted thoracic vertebrae were dissected systematically. One
      implanted spinal column was sectioned sagittally through the costotransverse
      space. The parietal pleura, the intercostal vessels, and intercostal nerves were
      not injured by the implants in any of the specimens. All the implants were
      located posterior to the intercostal nerves and vessels, lateral to the pedicles,
      and outside the spinal canal. The transverse processes of T1-T10 are safe
      structures for implant anchorage in posterior spinal instrumentation.

PMID- 8877956
TI  - The spinal nail: a new implant for short-segment anterior instrumentation of the
      thoracolumbar spine.
AB  - The biomechanics of a new spinal implant were evaluated and its dependence on an
      anterior strut graft was determined. Six fresh-frozen adult porcine spines were
      used. An L3 corpectomy was created. The spinal nail was inserted intraosseously
      into the middle column of the L2-L4 vertebral bodies in a trough. Implant drill
      holes were made for proximal and distal locking bolts in L2 and L4. A locking
      plate bridged the L2 and L4 trough and anchored the exposed ends of the locking
      bolts. Testing was performed in axial compression, torsion, and flexion. The
      axial and torsional stability of the spine instrumented with the spinal nail are
      similar to results with other devices when used with anterior strut grafting. The
      axial and flexural stiffnesses of the instrumented spine are independent of strut
      grafting. This study suggests that this device may be useful for reconstruction
      of the anterior spine because of instability.

PMID- 8877957
TI  - Strength, mobility, their changes, and pain reduction in active functional
      restoration for chronic low back disorders.
AB  - The association between subjective experience in pain reduction and objective
      measurements in improvement of physical functioning was analyzed with chronic low
      back pain (CLBP) patients (n = 143) who attended a 12-week multidimensional back
      treatment program emphasizing active functional restoration. Low back flexion
      extension, lateral flexion and rotation, isometric strength, and mobility and
      their changes were measured. The results showed that 79% of the subjects reported
      subjective decrease in LBP during the 12-week restoration program, and
      simultaneous increases in isometric strength and mobility also were measured in
      approximately 80% of the subjects. Concordance of these findings was high, i.e.,
      the reduction of pain and improvement of function occurred mostly in the same
      subjects. However, the correlations between physical functioning parameters and
      pain reduction were low (rs below 0.22). Baseline strength and mobility values
      did not differ between those who benefited from the treatment regarding pain and
      those who did not. Thus, absolute levels at the baseline or magnitude of changes
      in the measurements of maximum isometric strength or mobility were not associated
      with pain reduction. The results indicate that subjective pain reduction is
      significantly associated with improvement per se in trunk muscle function and
      spinal mobility during active functional restoration, but not with the magnitude
      of the improvements. This should be considered when designing rehabilitation
      programs and outcome criteria for rehabilitation.

PMID- 8877954
TI  - Day surgery for cervical microdiscectomy: is it safe and effective?
AB  - The objective of this pilot study was to evaluate the safety and efficacy of
      cervical discectomy with fusion performed on an outpatient basis. The
      experimental group (50 consecutive patients) was studied prospectively and the
      outcomes were compared with 53 consecutive, retrospectively analyzed, admitted
      controls who underwent the same procedure. Outcomes for both groups were assessed
      by patient-response questionnaires and clinical examination. At follow-up times
      of 1.3 (outpatient) and 1.6 (inpatient) years, outcomes (outpatient/inpatient)
      expressed as percent successful were as follows: Relief of arm pain (80/70%);
      relief of neck pain (78/68%); relief of arm muscle weakness and atrophy (94/96%);
      return to normal activities (64/70%); return to work (65/68%); and satisfaction
      with the results of surgery (86/83%). No statistically significant differences
      between outpatients and inpatients were found for any of the outcome parameters
      studied. There was no mortality and the operative complication rate was 2% for
      each study group. The results indicate that conversion of cervical discectomy
      with fusion from an admitted to an ambulatory practice did not compromise the
      safety or efficacy of the surgical procedure. Potential economic savings to
      overall health costs of the United States that might result from such conversion
      could exceed $100 million annually.

PMID- 8877958
TI  - Histologic changes in the disc after cervical spine trauma: evidence of disc
      absorption.
AB  - We examined the histologic changes in the disc in two cases of traumatic cervical
      disc herniation and compared it with previous histologic studies done in
      degenerative disc herniations. Differences in the absorption of herniated
      cartilage endplate and annulus fibrosus are also discussed. The herniated disc
      material was surrounded by fibrovascular tissue. Vessels in this fibrovascular
      tissue were seen to continue into the annulus fibrosus but not into the endplate.
      Scattered cartilage fragments and macrophages in the fibrovascular tissue were
      localized around the margin of the disc. The herniation produced a visible defect
      in the injured intervertebral disc. On serial sections, the amount of herniated
      annulus fibrosus appeared to be smaller than the defect produced in the annulus
      fibrosus of the injured disc. However, the herniated endplate seemed to be the
      same size as the defect produced in the endplate of the injured disc.
      Fibrovascular tissue formation, vessel infiltration into annulus fibrosus, and
      the presence of peripheral macrophages suggest marginal absorption. The cartilage
      fragments are probably remnants of disc tissue produced during the process of
      absorption. These findings are similar to that seen in degenerated herniated
      discs and suggest an absorptive process. Absorption of the annulus is more
      significant than absorption of the endplate.

PMID- 8877959
TI  - Usefulness and reliability of neurological signs for level diagnosis in cervical
      myelopathy caused by soft disc herniation.
AB  - We retrospectively analyzed neurological signs of 106 patients with cervical
      myelopathy caused by single-level soft disc herniation. Neurological signs that
      were intensively analyzed were deep tendon reflexes, the uppermost level of
      impaired pinprick sensation, the uppermost weak muscle, and region of numbness in
      the hands. Characteristic signs for each intervertebral level were deduced, and
      sensitivity, specificity, and accuracy of these signs were calculated. Deep
      tendon reflexes were specific signs for each intervertebral level, although not
      as sensitive as the neurological signs. Muscle weakness and pinprick sensation
      were neither sensitive nor specific. Hand numbness was moderately sensitive and
      specific. On the whole, there was no neurological sign that was both highly
      sensitive and specific for an intervertebral level, and therefore, neurological
      level diagnosis in cervical myelopathy should be performed comprehensively
      according to more specific signs, i.e., deep tendon reflexes and hand numbness.

PMID- 8877960
TI  - Rib graft or cement to enhance screw fixation in anterior vertebral bodies.
AB  - This study analyzed the use of a rib graft or cement to enhance the holding power
      of a screw in a vertebral body. The results were correlated to provide a
      rationale for surgically enhancing the holding power of a screw when stripping of
      the bone thread has occurred. Human lumbar vertebral bodies obtained at autopsy
      were used in this study. The screws were inserted at three different sites of
      each vertebra and a load necessary to strip the thread was applied. Then costal
      fixation and cement fixation were tested to determine whether it was possible to
      restore the ability of the screw to withstand pullout load in the same hole. The
      main finding was that methacrylate placement or costal fixation restored the
      ability of the screw to withstand pullout load to within 5% (cement) or 15% (rib
      graft) of the original value. These results validate the possibility of using a
      rib graft or cement to enhance screw fixation.

PMID- 8877961
TI  - Vertical transmission of the hip rolls due to wearing of TLSO for scoliosis.
AB  - Cosmesis is important in the treatment of adolescent patients with idiopathic
      scoliosis. It has been shown that although bracing reduces the rib hump, it
      induces several complications. The aim of this study was to describe a new
      disturbing complication due to wearing a thoracolumbosacral orthosis (TLSO) for
      adolescent idiopathic scoliosis: the vertical transmission of the hip rolls
      (trochanteric lipomatosis) in girls and its pathogenetic mechanisms. Trochanteric
      lipomatosis is common in the female population, particularly after adolescence,
      and is responsible for the characteristic appearance of the hip rolls. No data
      have been reported concerning vertical transmission of normal trochanteric
      lipomatosis with subsequent disturbance of aesthetic appearance while wearing the
      TLSO. In this prospective study, 300 consecutive adolescent girls who were
      treated with the TLSO for progressive idiopathic scoliosis were followed and
      evaluated for development of any vertical transmission of the hip rolls after
      application of the brace for an average of 2.5 years after termination of the
      treatment. Almost simultaneously, 290 age-matched, randomly selected adolescent
      girls served as controls and were examined by two unbiased observers during the
      school screening program to estimate the prevalence of trochanteric lipomatosis
      in female adolescents of the same geographic area. In this series, bracing
      reduced the thoracic scoliosis from 34.4 +/- 5 degrees to 18.5 +/- 6 degrees and
      the lumbar scoliosis from 29.4 +/- 4 degrees to 16.7 +/- 4 degrees 6 months after
      initiation of brace wearing. The average prevalence of normal trochanteric
      lipomatosis in girls in the control group was 26% (range, 12.2-68.4%) for the
      ages 9-14 years and was increasing with the age and weight. No correlation was
      found between amount of reduction of scoliosis and prevalence of the
      complication. Vertical transmission of the hip rolls was observed in 69 (23%) of
      the girls with scoliosis 6 months after initiation of brace wearing and was
      positively correlated with the rigidity of the scoliotic curvature (p < 0.05) and
      the amount of reduction of the curvature (p < 0.05). Seven (8.8%) girls
      discontinued brace wearing because of psychological distress related to the
      deformity around the hip rolls, whereas 51 (73%) additional girls underwent
      suction lipoplasty during or after the termination of the brace wearing, because
      of persistent and disturbing lipomatosis. Recurrence of significant lipomatosis
      was observed in 3 (5.8%) of the girls who underwent lipoplasty. Physicians who
      are involved with treatment of scoliosis with bracing should be aware of this
      aesthetic complication. Brace wearing should not attempt maximum correction of
      scoliosis, thus avoiding excessive force on the body, and should be ordered only
      in patients with immature spines, curves of > 25 degrees, and radiologically
      justified progression. Suction lipoplasty seems to be a safe method of treatment
      and should be advised in cases with unaesthetic vertical transmission of the hip
      rolls.

PMID- 8877962
TI  - Accuracy of pedicle screw placement with the assistance of lateral plain
      radiography.
AB  - To determine the accuracy of pedicle screw placement with the assistance of
      lateral plain radiography, a prospective study was performed between June 1991
      and March 1994 on patients who had undergone pedicle screw fixation of their
      thoracolumbar spine for degenerative and traumatic conditions. Sixty-five of 72
      patients had the appropriate imaging studies, including an intraoperative lateral
      plain radiograph and a post-operative computed tomography scan to evaluate
      pedicle screw placement. A total of 238 screws were inserted from the T11 to L5
      vertebral levels. Twenty-four screws penetrated the pedicle wall (18 medial and 6
      lateral) and two screws penetrated the anterior vertebral body cortex, for an
      overall 89.1% success rate. Only two patients had neurologic complications
      consistent with canal intrusion of a pedicle screw, corresponding to a 0.84%
      neurologic complication rate. Imaging techniques such as fluoroscopy and
      anteroposterior plain radiographs, which may increase the incidence of infection
      from prolonged operative time, are unnecessary in uncomplicated cases. Pedicle
      screw insertion in the thoracolumbar spine with the use of lateral plain
      radiography alone is safe and effective, and it minimizes operative time and
      expense.

PMID- 8877963
TI  - Massive tongue swelling as a complication after spinal surgery.
AB  - We report four cases of massive tongue swelling after spinal surgery. Swelling
      resulted from the position of the spine during surgery (flexed thoracic-cervical
      position), fixation of the endotracheal tube, additional surgical gauzes packed
      around the endotracheal tube, and compression of the base of the tongue.
      Swelling, which causes obstruction of the airway, is a severe complication after
      spinal surgery that sometimes requires a tracheotomy. This complication can be
      avoided by careful positioning of the patient and by fixation of the endotracheal
      tube before surgery. Once swelling of the tongue occurs, administration of a
      corticosteroid is effective in preventing construction of the airway.

PMID- 8877964
TI  - The value of magnetic resonance imaging of the postoperative spine with titanium
      implants.
AB  - Magnetic resonance (MR) evaluation was performed on patients with titanium spine
      implants. The objective was to determine the value of conventional MR for
      evaluating the postoperative spine with titanium implants. The value of MR
      imaging for evaluation of the postoperative spine without metal implants is well
      known. The results of MR evaluation of the titanium instrumented spine have not
      been explored. Thirty patients with titanium spine implants underwent MR
      evaluation. Indications included pain, neurologic deficit, decompression
      evaluation, and infection. The titanium implants caused only local MR signal void
      and did not interfere with the imaging of the adjacent soft tissues. This
      provided significant information and helped determine whether further surgical
      intervention was required. There is significant value of MR evaluation of the
      post-operative spine without compromise from titanium implants.

PMID- 8877965
TI  - Relapsing pancreatitis after combined anterior and posterior instrumentation for
      neuropathic scoliosis.
AB  - We report a case of pancreatitis in a 28-year-old woman who underwent a combined
      anterior Zielke procedure followed by Luque-TSRH (Texas Scottish Rite Hospital)
      operation in the same session for severe polioscoliosis. To our knowledge, only
      one case of a child with acute pancreatitis after posterior instrumentation for
      spondylolisthesis has been reported. In the early postoperative period, the
      patient developed acute pancreatitis that was diagnosed by a marked increase in
      plasma amylase and was confirmed by ultrasonography. The symptoms of pancreatitis
      in this patient temporarily resolved a few weeks after conservative treatment
      (diet, infusions, antibiotics). Six, 16, and 32 months after the combined
      operation, there were repeated relapsing episodes of pancreatitis with elevated
      amylase levels and concomitant symptoms. In the last follow-up evaluation in
      December 1995, the patient was well and the amylase levels were within normal
      limits. Although the etiology of pancreatitis in this case is obscure, we believe
      that the correction of the severe biplane spinal deformity, achieved by the two
      major operations on the spine in the same session, may have contributed to the
      pathogenesis of the disease. This observation suggests that pancreatitis after
      major scoliosis surgery should be suspected when abdominal symptoms persist
      associated with elevated serum amylase levels. Some cases of acute pancreatitis,
      such as this case, can persist in chronic-relapsing form for long periods
      postoperatively.

PMID- 8877966
TI  - Scoliosis induced by rib resection in chickens.

PMID- 8877967
TI  - Characterization of the feline herpesvirus type 1 immediate early gene
      expression.
AB  - We analyzed the mechanism for feline herpesvirus type 1 (FHV-1) immediate early
      (IE) gene expression. We demonstrated that (i) the transcription initiation site
      of the FHV-1 IE transcript lies in the putative FHV-1 ICP4 binding site, (ii) the
      FHV-1 IE transcript is spliced to remove 906 bp intron from the leader region,
      (iii) cis-acting elements of the FHV-1 IE promoter map both down- and upstream of
      the transcription initiation site, and (iv) a deletion of a 58 bp sequence which
      includes the putative FHV-1 ICP4 binding site in the IE promoter resulted in
      significant induction of promoter activity by a FHV-1 IE gene product although
      the FHV-1 IE gene product slightly stimulates the FHV-1 IE promoter, indicating
      that the FHV-1 IE gene product down-regulates its own promoter via the region.

PMID- 8877968
TI  - Prognosis of malignant mammary tumor in 53 cats.
AB  - Medical records of fifty-three cats diagnosed as malignant mammary tumor from
      1982 to 1993 were reviewed. The mean age of the cats at diagnosis was 11.1 years,
      and Japanese domestic and Siamese breeds were predominant. Survival rates after 1
      and 2 years of diagnosis were 31.8% and 17.7%, respectively, suggesting poor
      prognosis of this malignancy. The survival time was significantly associated with
      tumor size or WHO clinical stage, but not with breed, age, or gender. Twenty-nine
      cats with pulmonary metastasis died within 5 months following metastatic
      detection. Postoperative prognosis was significantly related to the tumor size at
      surgery, but not with type of surgery and adjuvant chemotherapy using
      cyclophosphamide and/or vincristine.

PMID- 8877969
TI  - Detection of circulating immune complexes in dog sera by immune adherence
      hemagglutination method.
AB  - Circulating immune complexes (CIC) in the sera from 102 clinically healthy dogs
      and from 16 Dirofilaria immitis (D. immitis) infected dogs were measured by the
      immune adherence hemagglutination (IAHA) method. The level of CIC in the sera
      from healthy dogs was 28.2 +/- 29.1 micrograms/ml. There was no significant
      difference in the levels of CIC regarding sexes or ages. On the other hand, the
      level of CIC in the sera from D. immitis infected dogs was 230.3 +/- 117.1
      micrograms/ml, which was significantly (p < 0.01) higher than that of healthy
      dogs. The results of this study confirm that IAHA method is one of the reliable
      means of detecting and/or diagnosing immune complex mediated diseases in dogs.

PMID- 8877970
TI  - Cytolytic activity induced by intramuscular injection of plasmid DNA expressing
      the nucleocapsid protein of the JHM strain of mouse hepatitis virus into C57BL/6
      mice.
AB  - We constructed plasmids expressing mRNA7 coding the nucleocapsid (N) protein of
      JHM strain of MHV (JHMV) under the control of Rous sarcoma virus (RSV) LTR or
      human elongation factor (EF) 1a promoter, referred to as pRSV-mRNA7 and pEF
      mRNA7, respectively. Although only a slight level of cytolysis was observed by
      the spleen cells from C57BL/6 mice injected intramuscularly with pEF-mRNA7, the
      spleen cells from the mice administered with pRSV-mRNA7 showed a significant
      level of cytolytic activities against the cells expressing the viral N protein.
      The difference in the level of specific cytolysis might have been mainly due to a
      difference in the expression levels of the N protein in the muscles between the
      mice injected with pEF-mRNA7 and pRSV-mRNA7, since the specific activity of
      chloramphenicol acetyltransferase (CAT) in muscles from the mice injected with
      plasmid DNA expressing CAT gene directed by RSV LTR was significantly higher than
      that in those administered by the plasmid DNA directed by EF-1a promoter.

PMID- 8877971
TI  - Early pregnancy diagnosis in the sow by saliva progesterone measurement using a
      bovine milk progesterone qualitative test EIA kit.
AB  - We attempted to measure the qualitative saliva progesterone concentration in the
      sow using a commercial bovine milk progesterone qualitative test EIA kit
      (qualitative kit), which can measure the progesterone concentration in
      approximately 10 min, and investigated the possibility of applying this method of
      progesterone concentration measurement to early pregnancy diagnosis in the sow.
      The accuracy of pregnancy diagnosis at 17-24 days after last mating for 138 sows
      was 91.3% (105/115) for positive cases and 100% (6/6) for negative cases. The
      overall pregnancy diagnosis accuracy, including 17 indeterminable cases, was
      80.4% (111/138). A comparison of the diagnoses based on progesterone
      concentrations measured by the qualitative kit and the saliva progesterone
      concentrations of identical samples measured by the quantitative kit showed close
      agreement: 6 cases diagnosed as negative pregnancy by the qualitative kit all had
      a progesterone concentration of less than 5 ng/ml, while 111 out of 115 cases
      diagnosed as positive pregnancy by the qualitative kit all showed a progesterone
      concentration over 5 ng/ml. Thus, the results of this study show that qualitative
      measurement of the saliva progesterone concentration in the sow using a bovine
      milk progesterone qualitative test EIA kit is a practical method for early
      pregnancy diagnosis.

PMID- 8877972
TI  - Ultrastructural observation of changes in (hepatic) peroxisomes by 3 to 90 days
      administration of bezafibrate in male rats.
AB  - Although many reports are available to indicate the increase in number and size
      of peroxisomes by oral administration of hypolipidemic reagents such as
      clofibrate and bezafibrate, the decrease in number and size of proliferated
      peroxisomes even during administration of these chemicals has not been well
      documented. The present study was aimed to detect when the decrease in number and
      size of peroxisomes would occur. In the present study, ultrastructural changes in
      hepatocytes of male Wistar rats during 3 to 90 days of oral administration of
      bezafibrate were analyzed by morphometric and cytochemical methods. By 3-day
      administration, the weight of the liver and the number and size of peroxisomes
      were significantly increased. These parameters began to decline from the time 14
      days of administration when the weight of the liver and the size of peroxisomes
      attained the peak. Heterogeneous catalase staining was most remarkable by 7-day
      administration. Mitochondria were another target cell organelle by bezafibrate.
      The total area of mitochondria was decreased by 3-day administration. However, by
      subsequent 7 to 90-day administration, it recovered almost the level of controls.
      By 90-day administration, many mitochondria had expanded cristae which contained
      filamentous substances.

PMID- 8877973
TI  - Slow-reacting and complement-requiring neutralizing antibody in swine infected
      with porcine reproductive and respiratory syndrome (PRRS) virus.
AB  - Various conditions were evaluated and modified to enhance the sensitivity of the
      neutralization (NT) test for detecting antibody in swine infected with porcine
      reproductive and respiratory syndrome (PRRS) virus. Higher NT antibody titers
      were consistently obtained by the addition of 10% (v/v) complement, fresh guinea
      pig serum, to the virus diluent and by the incubation of serum-virus mixture at 4
      degrees C for 24 hr. The appearance and persistence of antibodies detected by the
      modified NT test showed a similar pattern to those of antibodies detected by the
      indirect fluorescent antibody (IFA) assay, although the antibody titers obtained
      by the former method were consistently lower than those obtained by the latter
      method. Slow-reacting complement-requiring NT antibody was detected in sera from
      pig 2 weeks after infection with PRRS virus. The slow-reacting complement
      requiring NT antibody in the early serum samples was sensitive to 2
      mercaptoethanol (2-ME), whereas the slow-reacting complement-requiring NT
      antibody in the late serum samples was resistant to 2-ME. The initial phase may
      represent the IgM response and the later phase a change to IgG. A NT test was
      developed in which serum-virus mixtures were incubated at 4 degrees C for 24 hr
      with complement; this gave an improved sensitivity over the previous incubation
      at 37 degrees C for 60 min.

PMID- 8877974
TI  - Influence of calcium concentration on the antimicrobial activity of lasalocid
      against Selenomonas ruminantium.
AB  - The present study was designed to examine the interaction between the effects of
      lasalocid and Ca2+ on the growth and structure of Selenomonas ruminantium HD-4.
      Lasalocid, at a dose of 10 microM, inhibited cell growth almost completely after
      12 hr incubation in the presence of relatively high extracellular concentrations
      of Ca2+ (from 5 to 50 mM), but only slightly reduced cell growth in the presence
      of 0.2 mM Ca2+. With Ca2+ alone, cell growth was also inhibited at 12 hr as a
      function of the concentration of Ca2+ over the range 5 to 50 mM. In cultures at
      mid-exponential phase, growth was markedly inhibited by the simultaneous addition
      of 10 microM lasalocid and 15 mM Ca2+, but only moderately inhibited by lasalocid
      in the absence of Ca2+. However, there was no significant effect on bacterial
      growth at the mid-exponential phase when Ca2+ alone was added to the incubation
      medium. In thin sections of cells treated with lasalocid in the presence of 15 mM
      Ca2+, abnormal cells were found with cytoplasmic voids and with an outer membrane
      detached from the inner membrane layer, this change in the outer membrane was
      also found in cells treated with lasalocid alone. There was no visible
      abnormality in the outer membrane in thin sections of Ca2(+)-treated cells, while
      most of these cells showed only a slight contraction of cytoplasmic material or a
      loss of cytoplasmic contents. These results indicate the presence of a
      synergistic effect between the actions of lasalocid and Ca2+ on cell growth,
      presumably due to induced cytoplasmic alterations.

PMID- 8877975
TI  - Cardiopulmonary responses to capsaicin instillation to the laryngeal lumen and
      their reflex mechanisms in rats.
AB  - Cardiorespiratory effects of capsaicin (CAPS) solution instilled into the larynx
      and the reflex mechanisms were investigated in rats with spontaneous breathing or
      under artificial ventilation. The first challenge with CAPS (100 micrograms/ml,
      20 microliters) markedly inhibited spontaneous breathing due to a considerable
      prolongation of expiration time (TE) (1785% of control) in all rats. Circulatory
      changes such as hypertension (mean systolic blood pressure-210 mmHg) and
      bradycardia (10.5% decrease in heart rate) were also elicited by the 1st
      challenge with CAPS. These changes were largely reduced by the second challenge
      of CAPS; but not abolished in 3 of 5 rats by bilateral section of the superior
      laryngeal nerves (SLNs) and recurrent laryngeal nerves (RLNs). The bradycardia
      and hypertension after the CAPS-instillation were able to be elicited to the same
      extent in rats in the absence of apnea under artificial ventilation. The
      bradycardia was entirely abolished by pretreatment with atropine injection, while
      the hypertension was largely inhibited by phentolamine and propranolol. These
      results demonstrated that the laryngeal and/or pharyngeal noxious stimulus could
      induce marked cardiorespiratory reflexes, where the circulatory changes could be
      elicited in the absence of apnea, suggesting the presence of eliciting mechanisms
      of circulatory changes independent on the occurrence of apnea. In addition, it
      was also suggested that those cardiorespiratory responses were mediated by the
      afferents such as unmyelinated C-fiber endings and thin myelinated fibers and by
      the efferents, both the parasympathetic and sympathetic nervous systems.

PMID- 8877976
TI  - The nucleotide sequence of the hemagglutinin gene of the LA strain of rinderpest
      virus, a seed virus strain used for vaccine production in Japan.
AB  - The sequence of the hemagglutinin (HA) gene of the LA strain of rinderpest virus
      (RPV) has been determined by the direct sequencing method. The amino acid
      sequence of the protein which it encodes displays conservation of its structural
      determinants with the HA proteins of the other RPV strains. The LA-HA protein was
      shown to have three conserved potential N-linked glycosylation sites, compared
      with four such sites in the HA protein of L strain. The glycosylation site at
      position 200 on the L-HA molecule is absent from its LA-HA counterpart, due to a
      lysine for an asparagine substitution. The HA proteins of L and LA strains were
      the same molecular weight as judged by mobility on SDS-PAGE, suggesting that the
      site at position 200 is not used for glycosylation.

PMID- 8877977
TI  - Primary brain tumors in two dogs treated by surgical resection in combination
      with postoperative radiation therapy.
AB  - Primary brain tumors in two dogs were surgically removed followed by
      postoperative radiation therapy. The two tumors were confirmed histologically to
      be astrocytoma and meningioma, respectively. After the surgery, the neurological
      status of each dog improved dramatically and a total dose of 40 Gy was delivered
      to the surgical site to treat residual tumor tissue. Although the dog with
      astrocytoma died 6 months after surgery due to unknown causes, the dog with
      meningioma has lived for over 24 months with a degree of neurological disorder
      less severe than that before treatment. These results suggested the effectiveness
      of this type of therapy on brain tumor in dogs and therapeutic modality should be
      positively planned to treat canine brain tumors.

PMID- 8877978
TI  - Detection of Marek's disease virus serotype 1 (MDV1) glycoprotein D in MDV1
      infected chick embryo fibroblasts.
AB  - Chick embryo fibroblasts (CEFs) infected with three strains of Marek's disease
      virus serotype 1 (MDV1), GA, Md5 and JM, were subjected to indirect
      immunofluorescence assay with monoclonal antibodies (MAbs) against MDV1 homolog
      of glycoprotein D (MDV1 gD) of herpes simplex virus. By the MAbs, a number of
      MDV1 gD-positive cells were detected in CEFs infected with GA, whereas only a few
      and no positive cells were detected in CEFs infected with Md5 and JM,
      respectively. The MDV1 gD in GA-infected CEFs was recognized as the band of 64
      kDa in immunoblot analysis using one of the MAbs. This is the first report that
      the MDV1 gD was detected in MDV1-infected cell cultures.

PMID- 8877979
TI  - The fractional inhibitory concentration index of antimicrobial agents for
      bacteria and Mycoplasma isolated from the nasal swabs of cattle with respiratory
      diseases.
AB  - We investigated the effect of thiamphenicol plus lincomycin (TP + LCM) and
      thiamphenicol plus tylosin (TP + TS) combinations using checker board method on
      the growth of Pasteurella (P.) multocida, P. haemolytica and Mycoplasma (M.)
      bovis by calculating the fractional inhibitory concentration index (FIC index).
      The results showed that the FIC indexes of the TP + LCM combination for P.
      multocida, P. haemolytica and M. bovis were 0.36 +/- 0.10, 0.72 +/- 0.09 and 0.81
      +/- 0.18, respectively. The FIC indexes of the TP + TS combination for P.
      multocida, P. haemolytica, and M. bovis were 0.79 +/- 0.20, 0.66 +/- 0.11 and
      0.32 +/- 0.14, respectively. Thus, these combinations are assumed to have a more
      synergistic or additive effect on bacteria growth than a single antimicrobial
      agent.

PMID- 8877980
TI  - Effect of a combination of antimicrobial agents for the treatment of respiratory
      disease in cattle.
AB  - Clinical effect of the administration of thiamphenicol (TP) and tylosin (TS) on
      bovine respiratory disease was investigated. Group I (n = 64) were administered
      TP (10 mg/kg) and TS (4 mg/kg), group II (n = 26) were given TP (5 mg/kg) and TS
      (2 mg/kg). For the control, TP group (n = 25) were given 20 mg/kg of TP and
      ampicillin group (n = 23) were given 10 mg/kg of ampicillin. As a result,
      improvement of clinical findings was more rapid and the cure rate was
      significantly higher in group I compared to those in the other 3 groups. These
      results showed that a combination therapy with minimal basic doses of TP and TS
      is very effective for some respiratory diseases in cattle.

PMID- 8877981
TI  - Intraovarian immunolocalization of steroidogenic enzymes in a Hokkaido brown
      bear, Ursus arctos yesoensis during the mating season.
AB  - Immunolocalization for four steroidogenic enzymes was performed on an ovary taken
      from a Hokkaido brown bear during the mating season. This specimen is considered
      to be in the follicular phase because of the presence of large follicles. In
      large follicles, cholesterol side-chain cleavage (P450scc) and 3 beta
      hydroxysteroid dehydrogenase (3 beta HSD) were immunolocalized in theca interna
      cells and granulosa cells. 17 alpha-hydroxylase/C17-C20 lyase cytochrome P450
      (P450c 17) was immunolocalized in theca interna cells but not in granulosa cells.
      Aromatase cytochrome P450 (P450arom) was immunolocalized only in granulosa cells.
      In medium follicles, however, P450scc and 3 beta HSD were immunolocalized only in
      theca interna cells, and the immunoreactivity of P450arom was detected in neither
      theca interna cells nor granulosa cells. Immunoreactivities of P450scc, 3 beta
      HSD and P450c 17 but not P450arom were detected in interstitial cells. This study
      suggests that estrogen biosynthesis takes place through interrelation between
      theca cells and granulosa cells and is explained by the so-called two-cell
      mechanism. Furthermore, the granulosa cells in large follicles have the
      capability for pregnenolone and progesterone biosynthesis, and the interstitial
      cell in the bear ovary is also a steroidogenic site.

PMID- 8877983
TI  - A high frequency of induction of chromosome aberrations in the fibroblasts of LEC
      strain rats by X-irradiation.
AB  - The LEC strain of rats (LEC rats), originally developed as a model for hereditary
      fulminant hepatitis, is highly sensitive to whole-body X-irradiation when
      compared to WKAH strain of rats (WKAH rats). The present results showed that
      frequencies of certain types of chromosome aberrations induced by in vitro X
      irradiation in the fibroblasts of LEC rats were higher than those of WKAH rats.
      In particular, frequencies of chromatid gaps and chromosome exchanges in LEC
      cells were higher approximately 4- to 5-fold and 6- to 8-fold, respectively, than
      those of WKAH cells.

PMID- 8877982
TI  - Serological analysis of canine distemper virus using an immunocapture ELISA.
AB  - As a rapid and sensitive method to detect canine distemper virus (CDV), an
      immunocapture enzyme-linked immunosorbent assay (ELISA) was performed. The
      sensitivity and specificity of the immunocapture ELISA were considered to be high
      enough. Virus neutralizing (VN) test was also established using the immunocapture
      ELISA. By using this test, the different cross VN titers between sera of dogs
      experimentally infected with the Onderstepoort strain and those with a field
      isolate of CDV were observed.

PMID- 8877984
TI  - Comparative study of rumen ciliates in buffalo, cattle and sheep in Egypt.
AB  - Rumen ciliates species and composition of the sheep, Friesian-cattle and water
      buffaloes in Egypt were surveyed. As a result, 7 genera with 18 species and 6
      formae in sheep, 10 genera with 28 species and 11 formae in cattle and 12 genera
      with 29 species and 7 formae in water buffaloes were detected. Twenty-two species
      were common in both cattle and buffaloes, while 12 species in sheep were common
      with the other ruminants. Entodinium spp., such as E. simplex, E. nanellum and E.
      exigum, appeared most frequently in every host. In general, Egyptian domestic
      ruminants had the rumen ciliate composition similar to that of domestic ruminants
      in temperate zone, though the water buffaloes had several tropical species such
      as Entodinium longinucleatum forma spinonucleatum. The ciliate density was
      estimated as 10(5)/ml in every host species.

PMID- 8877985
TI  - The iothalamate clearance in cats with experimentally induced renal failure.
AB  - Plasma iothalamate (IOT) disappearance rates were measured after a single
      injection of IOT (113.8 mg/kg, IV) in cats with experimentally induced renal
      failure. The disappearance rates especially fitted into the one compartment
      model. The mean value of plasma disappearance rates of IOT in these cats with
      induced renal failure (2.16 +/- 0.240 x 10(-3) micrograms/ml/min) was markedly
      lower than that of clinically healthy cats (4.10 +/- 1.00 x 10(-3)
      micrograms/ml/min). These results demonstrate that IOT clearance is available for
      evaluation of renal function in cats.

PMID- 8877986
TI  - Serological property and replication in cell cultures of porcine reproductive and
      respiratory syndrome viruses isolated in Japan.
AB  - The serological property and replication in swine alveolar macrophages (SAM) and
      MARC-145 cell cultures of 35 porcine reproductive and respiratory syndrome (PRRS)
      viruses isolated in SAM were investigated. All the isolates were reacted almost
      equally with antisera against three Japanese isolates including EDRD-1 strain
      (American type) in immunoperoxidase monolayer assay (IPMA), but weakly or did not
      react with antiserum against Lelystad virus (European type) indicating that the
      Japanese isolates are more closely related to an American type virus. Twenty two
      of 35 isolates replicated with CPE both in SAM and MARC-145 cells, whereas
      remaining 13 isolates did not show CPE in MARC-145 cells. The antigenicity of the
      isolates did not relate to the virus origin and the replication in the cell
      cultures.

PMID- 8877987
TI  - Pathologic changes in closed porcine intestinal loops inoculated with Aujeszky's
      disease virus.
AB  - Development of enteric lesions in closed jejunal and ileal loops inoculated with
      Aujeszky's disease virus (ADV) was examined in four 6-week-old SPF pigs. A large
      number of ADV antigens were detected first in necrotic foci in the subepithelial
      areas, and subsequently in the epithelial cells, lymphoid follicles in Peyer's
      patches and neuronal cells of Meissner's and Auerbach's plexuses.

PMID- 8877988
TI  - A frozen-thawed in vitro-matured bovine oocyte derived calf with normal growth
      and fertility.
AB  - The growth and fertility of a female calf obtained from a frozen-thawed bovine
      oocyte was assessed. The birth weight of the calf was lower than the mean birth
      weight of calves from in vitro fertilized embryos (IVF-controls) and calves
      obtained by artificial insemination (AI-controls). The growth rate of the calf up
      to 6 months was slower than that of the IVF-controls, but similar to that of the
      AI-controls. When the calf developed into a heifer (200 kg), she was inseminated
      with frozen semen and 280 days later delivered a male calf. The chromosoms of
      this cow were normal. These findings suggest that the growth and fertility of the
      calf derived from the frozen oocyte are normal.

PMID- 8877989
TI  - Pemphigus foliaceus with typical histological and immunohistological findings in
      a dog.
AB  - A seven-year-old female mongrel dog showed incurable skin lesions for about a
      year. The lesions were at nasal bridge and periocular area, and were composed of
      crust formation and scaling. Biopsy specimens from the skin lesions possessed
      with multiple intraepidermal pustules containing many acatholytic keratinocytes.
      Direct immunoperoxidase stain using paraffin-embedded section showed IgG
      deposition at the intercellular area of upper epidermis and follicular
      infundibula. IgG was not detected at basement membrane zone. Clinical and
      pathological findings of the present case were identical to those of pemphigus
      foliaceus, an uncommon pustular autoimmune skin disease.

PMID- 8877991
TI  - Short- and long-term hemodynamic response to octreotide in portal hypertensive
      patients: a double-blind, controlled study.
AB  - This randomized, double-blind, placebo-controlled study on the hemodynamic effect
      of two different doses of octreotide administered subcutaneously was conducted
      among 20 cirrhotic portal hypertensive patients. The wedged hepatic venous
      pressure, the hepatic venous pressure gradient, the mean portal venous flow
      velocity, the resistive index of the superior mesenteric artery, the heart rate
      and the mean arterial pressure were simultaneously evaluated by hepatic vein
      catheterization and Doppler flowmetry at baseline, 30 and 45 min after a
      subcutaneous injection of octreotide [0.10 mg (7 patients), 0.05 mg (7 patients)]
      and of a placebo (6 patients). The portal blood flow velocity, the resistive
      index of the superior mesenteric artery, the heart rate and the mean arterial
      pressure were also measured 2, 4, 6 and 8 h after the injection. The hemodynamic
      changes observed 30 min after the injection did not differ from those at 45 min
      and the changes at 2, 4, and 6 h were similar to those at 8 h. A statistically
      significant decrease, in comparison to the placebo group, was observed 45 min
      after the injection of the two doses of octreotide in the wedged hepatic venous
      pressure (cumulative median decrease: -10%, p < 0.005), in the hepatic venous
      pressure gradient (cumulative median decrease: -10%, p < 0.005) and in the mean
      portal flow velocity (cumulative median decrease: -11%, p < 0.005). A significant
      increase in the resistive index of the superior mesenteric artery was observed 45
      min after the injection of the two doses of octreotide (cumulative median
      increase: +10%, p < 0.005). Lower, but significant changes in the mean portal
      flow velocity and in the resistive index of the superior mesenteric artery
      persisted until 8 h after the injection of the two doses of octreotide
      (cumulative median decrease of mean portal flow velocity: -7%, p < 0.005 and
      cumulative median increase of resistive index of the superior mesenteric artery:
      +4%, p < 0.005). Changes in the wedged hepatic venous pressure, the hepatic
      venous pressure gradient, the mean portal flow velocity and the resistive index
      of the superior mesenteric artery showed a great variability among patients.
      These changes were more pronounced in patients injected with the lower dose with
      no relationship with the plasma drug concentrations. Responder patients showed a
      significant higher baseline mean portal flow velocity in comparison with
      nonresponders (15.2 +/- 1.7 cm/s vs 11.3 +/- 1.3 cm/s; p < 0.005).

PMID- 8877990
TI  - Molecular basis of subcellular localization of HCV core protein.

PMID- 8877992
TI  - Large encapsulated hepatocellular adenoma in a male.

PMID- 8877993
TI  - Serum levels of endothelial injury markers creatine kinase-BB and soluble
      thrombomodulin during human liver transplantation.
AB  - Endothelial damage within the sinusoids of the liver probably plays a key role in
      primary liver dysfunction following transplantation. The aim of this work was to
      study the serum levels of two potential markers of endothelial damage, creatine
      kinase-BB and soluble thrombomodulin, during human graft revascularization.
      Thirteen human liver grafts were preserved in UW solution (mean time: 13.8 h).
      Creatine kinase-BB and transaminase activities and soluble thrombomodulin levels
      were measured: 1) in effluent and 2) in serum samples sequentially collected
      before revascularization, then during the first 120 min of revascularization and
      first post-operative week. No correlation was observed between serum values
      (peak) and effluent values. In serum, pre-operative creatine kinase-BB activities
      were correlated with soluble thrombomodulin levels (p = 0.01). Both increased
      significantly during the first minutes of the revascularization, then decreased
      markedly. In contrast, AST activity was maximal at day 1. This detectable and
      early release of creatine kinase-BB and soluble thrombomodulin in blood is in
      keeping with the early occurence of endothelial damage. Together with previous
      data, these findings suggest that serum determination of these two markers may be
      a useful tool in the assessment of endothelial injury in liver transplantation.

PMID- 8877994
TI  - Circulating HCV-RNA, HCV genotype, and liver histology in asymptomatic
      individuals reactive for anti-HCV antibody and their follow-up study.
AB  - The present study was aimed to clarify the virologic status, liver histologies,
      and the results of follow-up liver tests in symptom-free individuals with anti
      HCV antibodies and normal liver tests. Forty-nine individuals with normal liver
      tests and positive second generation anti-HCV antibody assay were entered into
      this study. Cases with hepatitis C viremia were evaluated for HCV genotype,
      amount of circulating HCV-RNA, and liver histology and were followed-up for more
      than one year. Of the forty-nine individuals, 36 had hepatitis C viremia,
      indicated by polymerase chain reaction (PCR) assay. Liver histology was as
      follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH),
      and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH
      developed an elevated AST and/or ALT concentration (> 30 IU/l) between 12 and 32
      months of follow-up. The amount of circulating HCV-RNA ranged from 10(2) to 10(7)
      copies/50 microliters serum. The distribution of HCV genotypes was nearly the
      same as that for symptomatic CAH. These data suggest that the histological
      examination and follow-up examination are very important for following symptom
      free individuals with hepatitis C viremia because there are some candidates for
      interferon therapy among them. There are few individuals who will remain healthy
      among asymptomatic HCV carriers.

PMID- 8877995
TI  - Iron stores, response to alpha-interferon therapy, and effects of iron depletion
      in chronic hepatitis C.
AB  - We studied 81 patients with chronic hepatitis C to investigate the relationship
      between iron and alpha-interferon response. Sixty-one patients (group A) were
      given alpha-interferon irrespective of iron status, whereas 20 (group B) with
      iron overload, were iron depleted before alpha-interferon therapy. In group A, 21
      patients responded to alpha-interferon and 40 were non-responders. Increased iron
      indices were significantly more frequent in non-responders than responders.
      Multivariate analysis showed that among the independent variables evaluated, only
      gamma-GT and liver iron concentration predicted therapy outcome. After phlebotomy
      treatment, serum alanine aminotransferase fell significantly both in patients of
      group B (196 +/- 122 IU/l vs 82 +/- 37 IU/l, p < 10(-6)) and in 12 non-responders
      of group A (198 +/- 89 IU/l vs 107 +/- 81 IU/l, p < 10(-6)). In 16 iron depleted
      patients, eight from each group, subsequent treatment with alpha-interferon
      produced a response in only one patient. These results suggest that increased
      liver iron is a negative prognostic factor for alpha-interferon response in
      chronic hepatitis C. Iron depletion had a beneficial effect on serum alanine
      aminotransferase in all the patients treated, but did not improve the response to
      alpha-interferon.

PMID- 8877996
TI  - Serum and cystic fluid CA 19-9 determinations as a diagnostic help in liver cysts
      of uncertain nature.
AB  - The distinction between hepatobiliary cystadenoma or cystadenocarcinoma and
      simple hepatic cyst complicated by intracystic hemorrhage may prove difficult to
      determine on the sole basis of clinical and radiological features because of the
      presence of intracystic structures and septations well-demonstrated by ultrasound
      examination in both situations. We investigated four patients with various types
      of hepatic cysts, in whom diagnostic difficulties led to further investigations.
      In this small group, CA 19-9 serum levels were abnormal only in the two patients
      with cystadenoma or cystadenocarcinoma. Cystic fluid CA 19-9 values were also
      five times higher in cystadenoma and cystadenocarcinoma than in other benign
      lesions. Our data thus suggest that the determination of serum and cyst fluid CA
      19-9 may be of help in distinguishing between hemorrhagic simple cyst and
      cystadenoma or cystadenocarcinoma.

PMID- 8877997
TI  - Quantitative measurement of human tissue hepatic blood volume by C15O inhalation
      with positron-emission tomography.
AB  - In order to estimate the tissue liver function, tissue hepatic blood volume was
      measured quantitatively and non-invasively using C15O inhalation in conjunction
      with positron-emission tomography. Fifty-eight patients with normal liver
      function, 14 patients with chronic hepatitis, 28 patients with hepatic cirrhosis,
      and 4 patients with obstructive jaundice were studied by positron-emission
      tomography scan after the single breath inhalation of 20 mCi of high specific
      activity 15O-labeled carbon monoxide. The mean tissue hepatic blood volume was
      significantly greater in patients with normal livers than in patients with
      chronic hepatitis or hepatic cirrhosis (mean: 20.5, 18.2, and 16.1 ml per 100
      cm3, respectively, p = 8.6 x 10(-8)). Tissue hepatic blood volume (tHBV)
      correlated with the reaction of the mesenchymal system and protein synthesis,
      because there was a potent correlation between tHBV and hepatic fibrosis. In
      normal livers, we were able to demonstrate significant differences in tissue
      hepatic blood volume among liver segments.

PMID- 8877998
TI  - Role of sympathetic cardiovascular tone in control of arterial pressure in rats
      with cirrhosis.
AB  - Although an increase in sympathetic nervous activity has been recognized in
      cirrhosis, the contribution of this overactivity to the regulation of arterial
      pressure is unknown. The arterial pressure response to increasing doses of
      hexamethonium (0.05 to 3.2 mg.kg-1.min-1), a ganglionic blocker that decreases
      sympathetic cardiovascular tone, was explored in normal rats and in two models of
      portal hypertension, i.e., rats with cirrhosis and rats with portal vein
      stenosis. Changes in plasma norepinephrine concentrations were greater in rats
      with cirrhosis (356 +/- 50 vs 166 +/- 30 pg/ml, p = 0.04) than in normal rats
      (186 +/- 23 vs 86 +/- 31 pg/ml, p = 0.06) and rats with portal vein stenosis (103
      +/- 37 vs 93 +/- 5 pg/ml, p = 0.10). The maximum decrease in arterial pressure
      was obtained at a dose of 1.6 mg.kg-1.min-1 in each group. However, the decrease
      in arterial pressure was significantly greater in rats with cirrhosis (-25 +/-
      2%) than in normal rats (-11 +/- 1%) and in rats with portal vein stenosis (-13
      +/- 2%) (p = 0.04). In conclusion, the results of this study suggest that the
      sympathetic cardiovascular tone is more important for the maintenance of arterial
      pressure in rats with cirrhosis than in normal rats and in rats with portal vein
      stenosis.

PMID- 8877999
TI  - Variation between centers in technique and guidelines for liver biopsy.
AB  - Hospitals have few published guidelines to follow when performing a liver biopsy.
      In 1992, we began revising our protocol in an effort to institute new guidelines
      for our teaching hospitals. To assess the current practice of liver biopsy, we
      sent 500 multilingual questionnaires to international academic centers, and 85
      U.S. centers were surveyed by telephone. The survey assessed: 1) patient
      preparation, 2) technical aspects of the biopsy, and 3) post-procedural care. One
      hundred and eighty international centers and 85 U.S. centers responded (total =
      265). We found a wide variation in the practice of this surgical procedure at
      both national and international centers. Many Asian centers (73%) performed a
      bleeding time prior to liver biopsy. This practice was seen in only 36% of the
      U.S. centers. Most centers preferred platelet counts of 50,000/mm3 and above. The
      aspiration needle was more widely used in the U.S. (74%) and in many
      international centers, but Asian centers (61%) preferred a cutting needle. Thirty
      percent of Japanese centers performed more than 50% of their liver biopsies
      laparoscopically. Few laparoscopies were done at other centers. While about a
      quarter of the reported U.S., European, Asian, and South American centers
      observed patients for 4-6 hours after a biopsy, the majority of centers observed
      patients 10 hours or more. In addition to the wide variation seen, this survey
      provided us with an academic view of the contemporary practice of liver biopsy
      and an insight into how to redefine our present guidelines.

PMID- 8878000
TI  - Immunogenicity and reactogenicity of a combined hepatitis A/B candidate vaccine:
      first results.
AB  - We evaluated immunogenicity and reactogenicity of an inactivated, combined
      hepatitis A/B candidate vaccine in 50 seronegative volunteers. Each volunteer
      received a total of three doses of vaccine (720 EIU HAV and 20 micrograms HBs
      antigen) according to a 0, 1 and 6 month vaccination schedule. One month after
      the first injection, the seroconversion rate was 90% (45/50) for anti-HAV and 28%
      (14/50) for anti-HBs, respectively. After the booster dose, at month 7, the
      seroconversion rate was as high as 100% (49/49) for anti-HAV and 94% (46/49) for
      anti-HBs. The geometric mean titres increased with each dose of vaccine
      administered. Mild, and mostly local side effects were reported in 54% of the
      volunteers after the first injection and in less than 10% after the third
      injection. Our results show that this inactivated, candidate hepatitis A/B
      vaccine is highly immunogenic and well-tolerated.

PMID- 8878001
TI  - Post-infantile giant cell hepatitis in patients with primary sclerosing
      cholangitis and autoimmune hepatitis.
AB  - In post-infancy, multinucleated giant cell hepatitis is rare. Various conditions
      and diseases associated with post-infantile giant cell hepatitis have been
      described, but the pathogenesis remains unknown. In this paper we review the case
      reports of four patients (3 male, 1 female; aged 22 to 32 years) with primary
      sclerosing cholangitis and autoimmune hepatitis. The follow-up ranges from five
      to seven years. All patients showed cholestasis and repeated elevation of hepatic
      transaminases. Patients with viral infections, metabolic disorders and toxic
      influences were excluded. Histopathology of liver tissue in all four patients
      revealed giant cell formation with up to 20 nuclei in 20-70% of all hepatocytes.
      Post-infantile giant cell hepatitis was defined histopathologically. The clinical
      course of all four patients markedly improved after immunosuppressive treatment.
      Further improvement was observed with the addition of ursodeoxycholic acid.
      Follow-up liver biopsies during treatment showed reduced inflammation and a
      decreased number of giant cells. One patient, who initially was admitted to the
      hospital with liver cirrhosis died five years later due to a sepsis. The clinical
      course of the other three patients remained stable during the observation period,
      and no progression of liver fibrosis was recorded as long as immunosuppressive
      treatment was continued. Cholestasis and autoimmunity seem to be two important
      mechanisms triggering hepatic giant cell formation in post-infancy. In the
      reported cases long-lasting cholestasis in primary sclerosing cholangitis
      together with features of autoimmune hepatitis seem to have triggered the
      formation of syncytial hepatic giant cells.

PMID- 8878002
TI  - Rapid hepatic failure associated with a contracted liver mimicking cirrhosis in a
      case of nasopharyngeal carcinoma with liver metastasis.
AB  - A 46-year-old women had an undifferentiated nonkeratinizing nasopharyngeal
      carcinoma, locally controlled by radiotherapy. Initially, she had normal liver
      function tests and normal hepatic ultrasonography. Seven months later, she
      experienced a rapidly progressive hepatic failure manifested by the development
      of ascites, elevation of serum bilirubin level, and prolongation of prothrombin
      time. Imaging studies showed a contracted liver and serum biochemical tests were
      compatible with chronic liver disease, except for an increase of alkaline
      phosphatase and gamma-glutamyl transpeptidase levels. An endoscopic retrograde
      cholangiogram ws compatible with changes of sclerosing cholangitis. The patient
      died of hepatic decompensation within two months. A liver necropsy disclosed
      diffuse infiltration of carcinoma cells into the hepatic sinusoids and
      obliterative angio-invasion of the tumor cells with massive fibrotic stroma
      replacing almost all hepatocytes. In situ hybridization demonstrated expression
      of Epstein-Barr virus transcripts EBER1 in the tumor cells and proved a
      metastatic nasopharyngeal carcinoma. The contracted liver is likely to be
      explained by the tumor-associated desmoplastic change and the obliterative angio
      invasion of the tumor. It is important to be aware that, although rare, such an
      unusual pattern of liver metastasis may mimick cirrhosis clinically and cause
      rapid hepatic failure in patients with nasopharyngeal carcinoma.

PMID- 8878003
TI  - Mononeuritis multiplex: a rare complication of acute hepatitis A.
AB  - A 28-year-old man suffered from acute severe hepatitis A virus infection,
      documented by serologic diagnosis. During the clinical and enzymatic recovery
      phase, mononeuritis multiplex that involved the left ulnar and right lateral
      cutaneous nerves developed. It presented by sensorimotor disturbances in left arm
      and right thigh. Mononeuritis multiplex has been frequently described in patients
      with chronic hepatitis B, either isolated or associated with periarteritis
      nodosa. However, it has not been reported in association with hepatitis A
      infection.

PMID- 8878004
TI  - Effect of magnesium on secretion of platelet-derived growth factor by cultured
      human arterial smooth muscle cells.
AB  - Two conditioned media were prepared by culturing human umbilical artery smooth
      muscle cells (SMC) in 75 cm2 flasks with minimum essential medium (MEM) under
      magnesium (Mg) sufficient (900 microM) or deficient (100 microM) conditions for
      72 h ([900]- and [100]-MEM), respectively. A third conditioned medium was
      obtained by adjusting the Mg concentration of half of the [100]-MEM to 900 microM
      ([100-900]-MEM). SMC in 12-well plates were incubated in one of the three
      conditioned media and the growth rates of SMC were determined by [3H]-thymidine
      incorporation and cell counting. The growth rate in [100-900]-MEM was
      significantly higher than in [900]- and [100]-MEM. When platelet derived growth
      factor (PDGF) was neutralized by the addition of a mixture of anti-PDGF-AA and 
      BB antibodies, [3H]-thymidine incorporation in [100-900]-MEM decreased by 23.3
      per cent, but only by 7.0 per cent in [900]-MEM. The quantity of PDGF in the Mg
      deficient media was greater than in the magnesium-sufficient media at all
      indicated times, as shown by radioimmunoassay for PDGF-BB or -AB. These results
      indicate that Mg deficiency increases the secretion of PDGF by SMC.

PMID- 8878005
TI  - Stability of free Mg2+ concentration and increased concentration of free Ca2+ in
      vascular smooth muscle cells during dietary magnesium deficiency in rat.
AB  - Intracellular free calcium and magnesium ion concentrations ([Ca2+]i and [Mg2+]i
      respectively) were estimated in thoracic aorta smooth muscle strips isolated from
      magnesium-deficient and control rats using fura-2/AM and mag-fura-2/AM,
      respectively. Adult male Wistar rats were fed a magnesium-deficient diet (10 mg
      Mg/kg diet) or a control diet (700 mg Mg/kg diet) for 30 days. Plasma magnesium
      level in magnesium-deficient rats was half of that in control rats at 30th day.
      Therefore, thoracic aorta strips, denuded of endothelium, were loaded with fura
      2/AM or mag-fura-2/AM in the presence of 0.5 or 1.0 mM Mg2+, and [Ca2+]i or
      [Mg2+]i was measured under the same Mg2+ conditions. The [Ca2+]i in the aorta
      strips isolated from magnesium-deficient rats in the presence of 0.5 mM Mg2+
      (254.9 +/- 13.1 nM) was approximately three times greater than in those from
      control rats in the presence of 1.0 mM Mg2+ (86.5 +/- 9.2 nM). The [Mg2+]i was
      not significantly different between the two groups at either Mg2+ level. The
      muscle tension and [Ca2+]i increased after [Mg2+]o was exchanged from 1.0 to 0.5
      mM; however, [Mg2+]i showed no change. The total calcium content increased and
      total magnesium content decreased in thoracic aorta strips isolated from
      magnesium-deficient rats. These results suggest that [Mg2+]i is stable, but that
      [Ca2+]i increases in vascular smooth muscle cells of thoracic aortas isolated
      from dietary magnesium-deficient rats.

PMID- 8878006
TI  - Intravenous magnesium sulphate and reperfused myocardium: preservation of
      function and reduction of infarct size.
AB  - The aim of the study was to examine the effects of intravenous magnesium sulphate
      (MS) administration on myocardial contractile function and infarct size after
      occlusion of the left circumflex artery of the heart for 60 minutes. Under sodium
      pentobarbital anaesthesia (30 mg/kg. intravenously) the hearts of mongrel dogs (n
      = 13) were instrumented to measure left ventricular pressure (LVP), regional
      contractile function of the territories perfused by the left circumflex and
      anterior descending coronary arteries (%SS), mean arterial pressure (MAP), and
      coronary blood flow velocity (CFV). Immediately upon release of the coronary
      occlusion, either intravenous magnesium sulphate (100 mg/kg) or a dextrose
      vehicle (D5W) was infused. Animals were killed, their hearts excised and cut in 1
      cm slices from apex to base and incubated in triphenyl tetrazolium chloride (TTC)
      for 20 minutes to measure infarcted areas. In the control group (n = 7),
      myocardial contractile function was severely depressed during the occlusion and
      displayed the same pattern of dysfunction during 3 h of reperfusion. The %SS of
      the area perfused by the circumflex artery at the end of the reperfusion period
      was 0.02 +/- 3 (mean + SEM) P < 0.05 vs MS; P < 0.05 vs pre-occlusion) and
      percentage of necrosis of the area at risk was 17.42 +/- 6 (P < 0.05 vs MS). In
      the magnesium sulphate group (n = 6), %SS was depressed during the occlusion as
      in the control group, but was preserved during reperfusion time, 9.8 +/- 1.0 (P <
      0.05 vs D5W; P < 0.05 vs pre-occlusion) and showed significantly less percentage
      of necrotic tissue, 4.53 +/- 1 (P < 0.05 vs D5W). These results suggest that
      intravenous magnesium sulphate preserves myocardial contractile function and
      reduces infarct size significantly following a period of complete coronary
      occlusion.

PMID- 8878007
TI  - Effects of long-term high manganese intake on magnesium metabolism in rats.
AB  - The effects of long-term high manganese intake on the magnesium metabolism in
      rats were studied. One group of rats was fed a normal diet and the treated group
      received a normal diet and distilled water containing 2 g/litre manganese (as
      MnCl2). Metabolic studies showed that after 11 weeks of treatment, manganese
      supplementation modified magnesium metabolism by increasing urinary magnesium
      excretion and decreasing magnesium balance.

PMID- 8878008
TI  - Disorders of magnesium homeostasis in the course of liver disease in children.
AB  - Magnesium deficiency can develop in patients with acute or chronic liver disease
      as a result of low dietary magnesium intake, low intestinal absorption or renal
      magnesium loss caused by natriuretic drugs. The aim of this study was to evaluate
      magnesium homeostasis in 39 children: 10 with acute liver failure due to Amanita
      phalloides poisoning. 14 with chronic liver diseases without cholestasis, and 15
      with chronic liver diseases with cholestasis. Serum magnesium and fractional and
      24 h urinary magnesium excretion were measured in all the children. Magnesium
      retention after intravenous infusion was also evaluated. Tissue magnesium deficit
      was found in 30 per cent of children with acute or chronic liver disease.

PMID- 8878009
TI  - Oral physiological magnesium supplementation for 6 weeks with 1 g/d magnesium
      oxide does not affect increased Lp(a) levels in hypercholesterolaemic subjects.
AB  - Twenty hyperlipidaemic patients on a cholesterol-poor diet were selected on the
      basis of a raised lipoprotein (a) (Lp(a); apo (a) > 300 U/litre) and treated with
      1000 mg MgO per day during 6 weeks. Serum magnesium slightly increased compared
      to pretreatment levels (P < 0.001). Serum apo(a) concentrations (mean +/- S.D.)
      were not affected: pretreatment level 963 +/- 552 U/litre; during treatment 999
      +/- 536 U/litre; and after washout 995 +/- 524 U/litre. Serum cholesterol
      increased slightly during MgO treatment because of an increase in LDL-cholesterol
      (10 per cent) and returned to pretreatment levels after a washout period.

PMID- 8878010
TI  - The osmotic and intrinsic mechanisms of the pharmacological laxative action of
      oral high doses of magnesium sulphate. Importance of the release of digestive
      polypeptides and nitric oxide.
AB  - A common use for high doses of oral magnesium salts is to produce a laxative
      effect to treat constipation. In the intestinal lumen the poorly absorbable
      magnesium ions (and other ions such as sulphate) exert an osmotic effect and
      cause water to be retained in the intestinal lumen. This increases the fluidity
      of the intraluminal contents and results in a laxative action. Although the
      laxative action of magnesium is thought to be due to a local effect in the
      intestinal tract, it is also possible that released hormones such as
      cholecystokinin or activation of constitutive nitric oxide synthase might
      contribute to this pharmacological effect. Under normal circumstances the
      pharmacological administration of high doses of oral magnesium salts is safe and
      some salts--such as magnesium hydroxide--also have an antacid effect to
      neutralize stomach acid. However, high doses of magnesium or prolonged use may
      allow sufficient absorption into the systemic circulation to cause renal or other
      organ toxicity.

PMID- 8878011
TI  - Antioxidant dietary status and genetic cardiovascular risk, or how an adequate
      intake of a-tocopherol, selenium, taurine, magnesium and various other natural
      antioxidants may overcome the deleterious metabolic consequences related to the
      E4-4 type of apolipoprotein E.

PMID- 8878012
TI  - Splicing glue: a role for SR proteins in trans splicing?

PMID- 8878013
TI  - Attaching and effacing of host cells by enteropathogenic Escherichia coli in the
      absence of detectable tyrosine kinase mediated signal transduction.
AB  - An unusual mutant of enteropathogenic E. coli (EPEC), deficient in its ability to
      invade host cells, was evaluated. The gene interrupted by the transposon in this
      mutant was located within a region of the EPEC chromosome devoted to secretion of
      proteins required for signal transduction. The mutant did not secrete detectable
      levels of the EspB protein, previously shown to be required for attaching and
      effacing, and did not induce detectable tyrosine phosphorylation of a 90 kDa host
      cell protein, previously associated with attaching and effacing and invasion. No
      quantitative or qualitative defect in the ability of the mutant to induce
      attaching and effacing effects was observed. Moreover, attaching and effacing by
      wild-type EPEC was unaffected by high doses of the tyrosine kinase inhibitor
      genistein. These results indicate that attaching and effacing activity can occur
      in the absence of detectable EspB secretion and tyrosine kinase mediated signal
      transduction.

PMID- 8878014
TI  - Cloning and detection of the hemolysin gene of Vibrio anguillarum.
AB  - A 5 kb DNA fragment encoding a hemolysin was cloned from the fish pathogenic
      bacterium Vibrio anguillarum using the cosmid vector charomid9-36. An open
      reading frame of the hemolysin gene (VAH1) was 2253 bp and corresponded to a
      protein of 751 amino acid residues. The deduced amino acid sequence of the VAH1
      gene and the previously reported Vibrio cholerae EI Tor hemolysin, V. vulnificus
      cytolysin-hemolysin, Aeromonas hydrophila AHH1 hemolysin, and A. salmonicida ASH4
      hemolysin showed a significant degree of sequence homology, and the overall amino
      acid identities were 57.3%, 25.8%, 46.2%, and 43.7%, respectively. DNA
      hybridization analysis under high-stringent conditions using VAH1 as a probe,
      demonstrated that VAH1 hybridized with 25 out of 28 strains of V. anguillarum
      including serotypes A to I, but did not hybridize with other species of Vibrio,
      A. hydrophila or A. salmonicida. The targeted DNA fragment of VAH1 was
      successfully amplified from V. anguillarum-infected fish tissues by PCR.

PMID- 8878015
TI  - Characterization of F18 fimbrial genes fedE and fedF involved in adhesion and
      length of enterotoxemic Escherichia coli strain 107/86.
AB  - Infection of susceptible weaned pigs with oedema disease strains of E. coli is
      associated with bacterial adhesion to the small intestine. F18 fimbria
      (previously named F107) was the first colonisation factor described on oedema
      disease strains, and its genetic determinant was cloned. In the present study,
      genes fedE and fedF were positioned in the F18 gene cluster, downstream of the
      major structural subunit gene fedA. Two fedE and two fedF mutants were identified
      that had lost their capacity to adhere to isolated porcine villi. Moreover, these
      mutants produced significantly longer fimbriae. In vitro adhesion tests, electron
      microscopy study, transcomplementation tests, and nucleotide sequence analysis
      indicated that proteins FedE and FedF are F18 minor subunits essential for
      fimbrial adhesion and effecting fimbrial length.

PMID- 8878016
TI  - Lactate enhancement of sialylation of gonococcal lipopolysaccharide and of
      induction of serum resistance by CMP-NANA is not due to direct activation of the
      sialyltransferase: metabolic events are involved.
AB  - Lactate enhances lipopolysaccharide (LPS) sialylation and induction of serum
      resistance in gonococci by CMP-NANA. To investigate whether the enhancement is
      due to a direct effect on the sialyltransferase, an improved extraction of the
      enzyme and a reliable quantitative assay were devised. Gonococci (strain F62)
      were disrupted in a French pressure cell and the bacterial membranes were
      extracted for 1 h at 37 degrees C with a detergent, NONIDET (1% v/v). The assay
      involved sialylation of LPS by CMP-14CNANA and scintillation counting of the
      labelled LPS after fixing it on filter paper strips by trichloracetic acid (TCA)
      and washing away unincorporated CMP-14CNANA. It was rapid, reproducible and,
      although the enzyme preparations contained endogenous LPS, was dependent upon
      added LPS for maximum activity. At 37 degrees C the rate was constant for up to 5
      min and proportional to the concentration of extract in the assay. A wide range
      of concentrations of lithium-L-lactate did not enhance the activity of the
      extracted sialyltransferase. At concentrations above 22 microM, it was
      inhibitory. Pre-incubation of gonococci with lactate enhanced subsequent LPS
      sialylation and induction of serum resistance by CMP-NANA. Hence, the process
      whereby lactate enhances the effect of CMP-NANA is separate from the action of
      CMP-NANA itself. Both processes were inhibited by a sublethal concentration of
      chloramphenicol, indicating that metabolic events are required. Evidently, the
      enhancement process does not involve a direct activation of the sialytransferase.

PMID- 8878017
TI  - Detection and localization of the EaeA protein of attaching and effacing
      Escherichia coli O45 from pigs using a monoclonal antibody.
AB  - The eaeA-positive, attaching and effacing (A/E) O45 E. coli isolates from pigs
      express an EaeA protein with an estimated molecular weight of 97 kDa. In the
      present study, a monoclonal antibody was raised against the EaeA protein of an
      A/E O45 isolate. Cross reaction of the monoclonal antibody with the EaeA protein
      of A/E strain of the rabbit (RDEC-1), but not with those of A/E strains of the
      human (E2348/69) and dog (89-4221), was observed. Reactions of the monoclonal
      antibody to A/E isolates in the O45 serogroup on the ELISA varied among isolates
      and appeared to be correlated with in vivo A/E capacity of these isolates. The
      EaeA protein of A/E O45 E. coli has an apparent isoelectric point of 8.4 and is
      exposed on the bacterial surface. The monoclonal antibody provides a useful tool
      for characterization of the EaeA protein of E. coli isolates from pigs.

PMID- 8878018
TI  - Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear
      cells and induction of a cytokine response.
AB  - In vitro infection of freshly isolated human peripheral blood mononuclear cells
      (HPBMC) with Chlamydia pneumoniae was found to induce a production of tumour
      necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6
      (IL-6) and interferon alpha (IFN-alpha). The secretion was dependent on the
      amount of infecting chlamydiae and most of it occurred during the first 12 to 24
      h. Lipopolysaccharide (LPS) of Salmonella minnesota Rechemotype, used as a
      positive control for HPBMC activation, induced a release of TNF-alpha, IL-1 beta
      and IL-6, but not of IFN-alpha, similar to the effect of C. pneumoniae. Viable
      chlamydiae could not be recovered from HPBMCs infected immediately after their
      isolation, whereas HPBMCs which were cultured in vitro for 3 to 9 days before
      infection were able to maintain the growth of C. pneumoniae. Growth inside HPBMCs
      as well as induction of cytokine response may have a role in the pathogenesis of
      C. pneumoniae infection.

PMID- 8878019
TI  - Hyperplastic mesothelial cells within abdominal lymph nodes: mimic of metastatic
      ovarian carcinoma and serous borderline tumor--a report of two cases associated
      with ovarian neoplasms.
AB  - Two cases of hyperplastic mesothelial cells within intra-abdominal lymph nodes
      were encountered in staging procedures in a 59-year-old woman with bilateral
      ovarian serous borderline tumors and in a 21-year-old woman with a Sertoli-Leydig
      cell tumor of intermediate differentiation. Both patients also had mesothelial
      hyperplasia of the pelvic and abdominal peritoneum; in one of them, the
      hyperplasia was striking. The intranodal mesothelial cells occupied the sinusoids
      of the lymph nodes and were initially suspected of being metastatic from the
      ovarian tumor in each case. The appearance of the cells on routine stains
      suggested the correct diagnosis, which was confirmed by histochemical and
      immunohistochemical staining. These cases represent the first reported examples
      of mesothelial cells within abdominal lymph nodes, although similar involvement
      of mediastinal lymph nodes has been described in three patients with pleural
      effusions. Intranodal mesothelial cells should be distinguished from metastatic
      tumor, an error that could result in inaccurate staging in a patient with a known
      tumor or prompt a futile search for an occult primary tumor. Moreover, it is
      important that in studies evaluating the frequency of nodal involvement by serous
      borderline tumors, intranodal mesothelial cells should not be misinterpreted as
      metastatic borderline tumor, a distinction that can be difficult with only
      routinely stained sections.

PMID- 8878020
TI  - Immunoreactivity of S100 protein, alpha-1-antitrypsin, and CD68 in adult and
      congenital granular cell tumors.
AB  - Some benign tumors categorized as "granular cell tumors" (GCTs) may have
      heterogenous origins despite their uniform morphologic appearance. Adult GCTs
      (the usual type), presumed to be of Schwannian origin, are reported to be
      positive for S100 protein (S100) and neuron-specific enolase (NSE). Congenital
      GCTs are S100- and NSE-negative and of unknown but probable non-Schwannian
      origin. To elucidate the histogenesis of adult and congenital GCT, we undertook a
      comparative immunohistochemical study using paraffin-embedded tissue from 10
      cases of GCTs, of which 3 were the congenital type, 6 were the adult type, and 1
      was an unusual multiple GCT involving the colonic mucosa. All of the GCTs were
      negative for keratin, smooth muscle actin, muscle-specific actin, desmin, CD57,
      CD15, and MAC387. All of the adult and multifocal GCTs involving the colonic
      mucosa were positive for S100, NSE, alpha-1-antitrypsin (A1AT), CD68, and
      vimentin. Congenital GCTs, on the other hand, were negative for S100 and NSE but
      positive for A1AT, CD68, and vimentin. Our study suggests that these two types of
      GCT have different histogeneses because S100 and NSE are positive in the adult
      type but negative in the congenital type. They share, however, a common
      immunophenotype of positive A1AT, CD68, and vimentin. Although this may seem to
      indicate a common histiocytic origin for adult and congenital GCT, another
      macrophage marker, MAC387, is negative. Furthermore, CD68 is closely related to
      the glycoprotein of the lysosomal membrane and is not completely specific for
      histiocytic cells; for example, it is positive in reactive and neoplastic Schwann
      cells. Thus, we conclude that positive immunoreactivity for A1AT and CD68 in GCT
      may be a reflection of the intracytoplasmic accumulation of phagolysosomes and
      that it does not imply a histiocytic origin for this tumors. We confirm that
      adult GCT is of Schwannian origin and that congenital GCT is of uncommitted
      mesenchymal cell origin.

PMID- 8878021
TI  - Effects of preoperative chemotherapy on the morphology of resectable breast
      carcinoma.
AB  - We examined pathologic specimens from 43 patients with Stage T1-T3 lesions who
      were treated preoperatively with four cycles of doxorubicin/cyclophosphamide,
      followed by segmentectomy/mastectomy and axillary node dissection (the National
      Surgical Adjuvant Breast and Bowel Project B-18 protocol). Specimens from 46
      patients treated post-operatively with the same regimen served as histologic
      controls. The initial diagnosis was made by core needle biopsy (28%) or by fine
      needle aspiration (72%). Six changes were noted in 36 patients (84%), with
      complete regression in 10, but histologic evidence of regression and
      characteristic cytologic changes occurred in only one-half of the 43 patients,
      and there was poor correlation between histologic regression and clinical
      response; (2) an increased nuclear grade occurred in 32% of the cases; (3)
      unusually prominent intraductal and/or intralymphatic tumor was observed in 40%;
      (4) histologic evidence of tumor regression in axillary lymph nodes was noted in
      nine cases; (5) regressive changes also occurred in non-neoplastic breast tissue
      and in lymphoid populations of lymph nodes; and (6) difficulty was noted in
      evaluating residual atypical intraductal proliferations. These findings add a
      quantitative dimension to previously published descriptions and emphasize the
      need for pathologic staging in these patients. In addition, they provide
      histopathologic evidence of downstaging in axillary lymph nodes and of relative
      treatment resistance by intraductal and intralymphatic tumor.

PMID- 8878022
TI  - The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas
      of the liver.
AB  - We performed immunohistochemical studies on 90 surgically resected liver tumors,
      including 30 tumors each from hepatocellular carcinoma (HCC), cholangiocarcinoma
      (CC), and metastatic colorectal adenocarcinoma (MCA), using monoclonal antibodies
      against cytokeratin (CK) 7, CK 19, and CK 20 to examine the differences in the CK
      expressions in primary and metastatic carcinomas of the liver. We also
      investigated the usefulness of such expression in the differential diagnosis in
      addition to existing markers such as alpha-fetoprotein, carcinoembryonic antigen,
      and carbohydrate antigen 19-9. For CK 7, all except for one (97%) of the CCs were
      diffusely positive, whereas only two (7%) HCCs and one (3%) MCAs were diffusely
      positive. For CK 19, 23 (77%) CCs and 19 (64%) MCAs were diffusely positive,
      whereas no HCCs were positive. For CK 20, 22 (74%) MCAs were diffusely positive,
      whereas no HCC and three (10%) CCs were diffusely positive. The findings
      concerning the expression of immunohistochemical CK are therefore considered to
      be useful in addition to the diagnostic criteria when making a differential
      diagnosis of primary and metastatic carcinomas of the liver.

PMID- 8878023
TI  - Interphase cytogenetic study of endometrial stromal sarcoma by chromosome in situ
      hybridization.
AB  - Endometrial stromal neoplasms include a heterogenous group of tumors with
      different clinical behavior and response to treatment. Cytogenetic study of such
      tumors has been scanty. The aim of this study was to analyze and compare the
      chromosome composition in low-grade and high-grade endometrial stromal sarcoma
      using the technique of chromosome in situ hybridization. Eight cases of low-grade
      stromal sarcoma and three cases of high-grade stromal sarcoma were studied.
      Biotinylated DNA probes specific for the regions of chromosomes X, 11, 12, and 17
      were used on formalin-fixed paraffin embedded material from these tumors. The in
      situ hybridization signals were visualized by immunoperoxidase technique. Four of
      the eight low-grade stromal sarcomas retained normal disomy of the chromosomes
      studied. The other four low-grade sarcomas showed a gain of from one to three
      chromosomes, whereas all of the three high-grade sarcomas showed polysomies in
      all of the four chromosomes being studied. No loss of chromosomes was detected.
      One case of high-grade sarcoma contained coexisting areas of low-grade sarcoma.
      Although aneusomy was found in the high-grade portion, disomy was noted in the
      low-grade areas. In the stromal sarcomas studied, there was no definite
      correlation between the presence of chromosome polysomies and the clinical
      progress of the tumors. This is the first interphase cytogenetic study of uterine
      stromal sarcoma, and the results support the concept that complex numerical
      chromosome abnormalities evolve during anaplastic transformation of endometrial
      stromal sarcoma.

PMID- 8878024
TI  - Predictive value of proliferation-related markers, p53, and DNA ploidy for
      survival in patients with soft tissue spindle-cell sarcomas.
AB  - In a retrospective study of 60 spindle-cell sarcomas of peripheral soft tissues,
      we evaluated the extent of immunostaining with antibodies against Ki-67,
      proliferating cell nuclear antigen, and p53 protein and flow-cytometric DNA
      ploidy, their relation to tumor location, depth, histologic type, size, mitotic
      rate, and extent of tumor necrosis, as well as their influence on survival.
      Although Ki-67-labeled nuclei were detected in only 41 tumors (68%) and their
      number varied from 1 to 50%, proliferating cell nuclear antigen immunoreactive
      nuclei were found in each tumor, with their number ranging from 20 to 99%. p53
      Protein was found in 26 cases (43%), and its labeling ranged from 1 to 80%.
      Although Ki-67 labeling significantly correlated with mitotic rate, no
      correlation could be found between proliferating cell nuclear antigen or p53
      labeling and any other variables studied. Thirty-eight percent of the tumors were
      diploid, and 64% were aneuploid. Factors that significantly reduced survival in
      univariate analysis were increasing size and depth of the tumor, the presence of
      necrosis, the National Cancer Institute grade, and a tetraploid/hypertetraploid
      DNA pattern. In multivariate analysis of 49 cases with complete information, only
      DNA ploidy pattern, tumor size, and tumor necrosis retained their independent
      prognostic significance.

PMID- 8878025
TI  - Use of CD23 (BU38) on paraffin sections in the diagnosis of small lymphocytic
      lymphoma and mantle cell lymphoma.
AB  - The CD23 antigen is a low-affinity immunoglubulin E receptor that is expressed
      during B-cell activation. Recently, it has been shown to be of diagnostic utility
      in distinguishing between small lymphocytic lymphoma (SLL) and mantle cell
      lymphoma (MCL), two entities that can have similar morphologic and
      immunophenotypic features. Such studies, however, generally required viable cells
      in cell suspension or cryostat sections for detection of CD23. We evaluated
      staining for the CD23 antigen in paraffin sections, using BU38, an antibody that
      detects a fixation-resistant epitope of the antigen. We analyzed 44 SLLs, 3
      lymphoplasmacytoid lymphomas, and 39 MCLs. Staining was performed on formalin- or
      B5-fixed paraffin-embedded tissue sections using L26 (CD20), CD3, Leu22 (CD43),
      and BU38 (CD23) antibodies. All of the cases were of B-cell phenotype (CD20+),
      and 42/44 SLLs, 3/3 lymphoplasmacytoid lymphomas, and 33/39 MCLs coexpressed the
      CD43 antigen. CD23 was positive in 41 (93%) of 44 SLLs. The majority of
      neoplastic cells (75% or more) stained positively, with a membranous pattern of
      staining. The staining was moderate in intensity and easily interpreted. Only
      1/39 MCLs and 1/3 lymphoplasmacytoid lymphomas were CD23 positive. CD23-positive
      follicular dendritic cells were, however, present in all of the MCLs, either in
      residual follicles or in large, disordered meshworks. These results demonstrate
      that the BU38 antibody can detect CD23 on the cells of SLLs in paraffin sections
      and that this antibody can have diagnostic utility in routine diagnosis.

PMID- 8878026
TI  - DNA analysis and S-phase fraction determination by flow cytometric analysis of
      infiltrating lobular carcinoma of the breast.
AB  - Flow cytometric analysis was performed on 50 infiltrating labular carcinomas
      (ILCs) of the breast from 50 patients with clinical follow-up (average duration,
      4.1 yr) who had been treated between 1976 and 1991. The patients were classified
      as alive with no evidence of disease, alive with disease, or dead of disease.
      Ploidy and S-phase fraction (SPF) were compared with clinical outcome, histologic
      pattern (classical versus variant patterns), nuclear grade 1 or 2, axillary lymph
      node status, tumor size, percentage of signet ring cells, and estrogen receptor
      status. There was no association between aneuploid or diploid ILC and disease
      recurrence (of those patients classified as alive with no evidence of disease
      plus dead of disease, 4 (40%) of 10 were aneuploid and 15 (38%) of 40 were
      diploid), survival (of those classified as alive with no evidence of disease plus
      alive with disease, 9 (90%) of 10 were aneuploid and 36 (90%) of 40 were
      diploid), or any of the other factors evaluated. However, ILCs with a high SPF
      were more likely to recur than those with a low SPF (a high SPF was found in 9
      [56%] of 16; a low SPF was found in 9 [30%] of 30), but this relationship was not
      statistically significant (P = 0.08). When only diploid ILCs were considered,
      there was a statistically significant association between high SPF and recurrence
      (a high SPF was found in 9 [64%] of 14, a low SPF was found in 6 [24%] of 25, P =
      0.033). After the stratification of the diploid ILCs by the stage of disease,
      this relationship persisted only in Stage 1 (recurrence: a high SPF was found in
      3 [75%] of 4; a low SPF was found in 1 [9%] of 11, P = 0.033). There was no
      association between SPF and any of the other factors evaluated. Our study
      indicates that ILC is usually diploid and that SPF may be a prognostic indicator
      that is limited to Stage 1 disease.

PMID- 8878027
TI  - In situ distribution of integrin alpha 2 beta 1 and alpha-actinin in melanocytic
      proliferations.
AB  - Integrin alpha 2 beta 1 is a transmembrane protein receptor for collagen and
      laminin previously reported as a melanoma tumor progression antigen. alpha
      Actinin is an actin-binding protein reported to interact with the cytoplasmic
      domain of the beta 1-integrin chain of alpha 2 beta 1. In vitro, both alpha 2
      beta 1 and alpha-actinin play a role in melanoma cell motility. In turn,
      increased melanoma cell line motility (measured as mean migration rates),
      correlates with metastasis. To determine the in situ distribution of these
      proteins, we used monoclonal antibodies directed against the alpha 2-integrin
      subunit of alpha 2 beta 1 and alpha-actinin on frozen sections of 33 melanocytic
      proliferations, which included dermal nevi, primary melanomas, and metastatic
      melanomas. We found that the superficial portion of all of the melanocytic
      proliferations tested stained for alpha-actinin. In benign nevi and superficial
      spreading melanoma, there was a notable loss of staining for alpha-actinin in the
      cells in the deep reticular dermis. In contrast, alpha-actinin was present on
      almost all of the tumor cells in the nodular melanomas and the melanoma
      metastases. Tumors stained either uniformly positive or uniformly negative for
      alpha 2 beta 1; the expression of this protein correlated with the later stages
      of melanoma progression. Our findings suggest that alpha-actinin protein levels
      initially decrease and then increase during melanocytic tumor progression,
      whereas the alpha 2 subunit protein appears in the later stages of melanoma
      progression. The variable distribution of these proteins is evidence for the
      differential adhesive and motile properties of subpopulations of cells in
      melanocytic proliferations.

PMID- 8878028
TI  - SNOMED-encoded surgical pathology databases: a tool for epidemiologic
      investigation.
AB  - Pathology departments have invested considerable energy, sometimes extending over
      several decades, toward coding their anatomic pathology reports. As a result of
      these labors, there is now a vast amount of electronically coded data from
      surgical pathology reports, holding a wealth of information relevant to virtually
      every recognized pathologic entity. The original intent of the Systematized
      Nomenclature of Medicine (SNOMED) was to prepare population-based disease data
      from pathology reports, but no such studies have emerged in the medical
      literature. This is due in part to the nonuniform, idiosyncratic, and incomplete
      manner in which most SNOMED databases are constructed. Automatic (computer
      driven) coding provides uniformity and completeness of SNOMED databases and
      offers the possibility of customized recoding for an entire collection of reports
      using any nomenclature and any set of coding algorithms. In prior investigations,
      we described a computer program that SNOMED-codes surgical pathology reports, and
      we provided an analysis of a large surgical pathology SNOMED database. In this
      report, we describe the importance of coded surgical pathology databases for
      research, teaching, hospital administration, and public health, and we explain
      the functional differences between coded databases and free-text collections of
      surgical pathology data. Surgical pathology departments and vendors of laboratory
      information systems can ensure that surgical report files can be automatically
      coded or recoded with any chosen nomenclature by adhering to simple guidelines.

PMID- 8878029
TI  - Broad-host-range plasmid replication: an open question.
AB  - Many factors can influence the ability of plasmids to colonize different hosts,
      efficient replication probably being the most critical one. Two major strategies
      seem to facilitate promiscuous plasmid replication: (i) initiation independent of
      host initiation factors; and (ii) versatile communication between plasmid and
      host initiation factors. Appropriate communication between a replicon and the
      different hosts, which becomes crucial at the initation of plasmid replication,
      plays a major role in plasmid promiscuity. Fused replicons or mechanisms that
      rescue collapsed replication forks may increase the efficiency of plasmid
      propagation. However, their contribution to plasmid promiscuous replication
      remains to be fully evaluated. Several examples of host-specific adaptation of
      promiscuous plasmids point to an enormous flexibility of these replicons.

PMID- 8878030
TI  - Three conserved consensus sequences identify the NAD-binding site of ADP
      ribosylating enzymes, expressed by eukaryotes, bacteria and T-even
      bacteriophages.
AB  - It has been previously reported that the three-dimensional structures of the NAD
      binding and catalytic site of bacterial toxins with ADP-ribosylating activity are
      superimposable, and that the key amino acids for the enzymatic activity are
      conserved. The model includes an NAD-binding and catalytic site formed by an
      alpha-helix bent over a beta-strand, surrounded by two beta-strands bearing a Glu
      and a His, or Arg, that are required for catalysis. We show here that the model
      can be extended to comprise all proteins with ADP-ribosylating activity known to
      date, including all eukaryotic mono- and poly-ADP-ribosyltransferases, the
      bacterial ADP-ribosylating enzymes which do not have toxic activity, and the
      analogous enzymes encoded by T-even bacteriophages. We show that, in addition to
      the common Glu and Arg/His amino acids previously identified, the conserved
      motifs can be extended as follows: (i) the Arg/His motif is usually arom-His/Arg
      (where 'arom' is an aromatic residue); (ii) in the sequences of the CT group the
      beta-strand forming part of the 'scaffold' of the catalytic cavity has an arom-ph
      Ser-Thr-Ser-ph consensus (where 'ph' represents a hydrophobic residue); and (iii)
      the motif centered in the key glutamic residue is Glu/Gin-X-Glu; while (iv) in
      the sequences of the DT group the NAD-binding motif is Tyr-X10-Tyr. We believe
      that the model proposed not only accounts for all ADP-ribosylating proteins known
      to date, but it is likely to fit other enzymes (currently being analysed) which
      possess such an activity.

PMID- 8878031
TI  - Two beginnings for a single purpose: the dual-start holins in the regulation of
      phage lysis.
AB  - For most large phages of both Gram-positive and Gram-negative bacteria, there
      appears to be a single pathway for achieving disruption of the host envelope,
      requiring at least two phage-encoded lysis functions (a holin and an endolysin).
      The holin is a small membrane protein which causes a non-specific lesion in the
      cytoplasmic membrane, which allows the endolysin to gain access to its substrate,
      the peptidoglycan. The scheduling of host lysis is effected by regulatory
      mechanisms which govern the synthesis and activity of the holin protein
      accumulating in the membrane. Accordingly, aspects of expression and function of
      holin genes are considered here, focusing mainly on the lambdoid S genes. This
      group of genes, of which lambda S is the prototype, are characterized by a dual
      start motif consisting of two Met start codons separated by one or two codons, at
      least one of which specifies Arg or Lys. Two protein products are elaborated,
      differing only by two or three N-terminal residues but apparently possessing
      opposing functions: the shorter polypeptide is the active holin, or
      lysiseffector, whereas the longer polypeptide apparently acts as an inhibitor of
      holin function. Models will be considered which may account for the ability of
      the holin to form a 'hole' in the cytoplasmic membrane at a programmed time, as
      well as for the inhibitory properties of the longer product. Finally, we discuss
      recent results suggesting that the dual-start motif can be viewed as a level of
      regulation superimposed on a timing function intrinsic to the canonical holin
      structure.

PMID- 8878032
TI  - Photobiology of microorganisms: how photosensors catch a photon to initialize
      signalling.
AB  - Photobiological processes are relevant for microorganisms for energy generation,
      protection against excess and/or damaging radiation, and for signalling. In this
      review we give an overview of the knowledge on the functioning of photosensors in
      microorganisms, with special emphasis on the conformational changes that lead to
      signal generation and transduction. Light is absorbed by specific chromophores,
      which are tuned, by their proteinaceous environment, to function optimally. These
      chromophores belong to three classes: tetrapyrroles, polyenes and aromatics. The
      chemical structure of photosensing pigment/protein complexes has been resolved
      for many of the photobiological processes that have a characteristic sensitivity
      in the visible and infrared part of the spectrum of (solar) radiation. However,
      knowledge about the structure of photoreceptors responsible for several
      physiologically well-characterized photoresponses to UV- and blue light is still
      lacking. For a limited number of phototransduction processes, the details of
      light-induced signal transfer are beginning to be understood in atomic detail.
      This applies particularly to two photosensors involved in phototactic responses
      in bacteria: sensory rhodopsin I (SR-I) from Halobacterium salinarium and
      photoactive yellow protein (PYP) from Ectothiorhodospira halophila. The SR-1
      system is of special interest because the transducer accepting the signal from SR
      1 was recently identified as Htr-1, a homologue of the methyl-accepting
      chemotaxis proteins which have been characterized in Escherichia coli. PYP, on
      the other hand, may be the first photosensor to actually reveal all relevant
      details of the kinetics, thermodynamics, and molecular motion of light-induced
      signal generation, through an understanding of how the photo-isomerization of the
      chromophore forces the sensor protein into the signalling state. Here we compare
      these photosensors and discuss common themes in the initiation of photosensory
      signal transduction in microorganisms in terms of the molecular properties of
      photosensors and their signalling state.

PMID- 8878033
TI  - Genetically probing the regions of ribose-binding protein involved in permease
      interaction.
AB  - The ribose-binding protein (RBP) of Escherichia coli, located in the periplasm,
      binds to ribose and mediates transport and chemotaxis. The regions on the
      tertiary structure of RBP that interact with the membrane permease, an ABC
      transporter, were genetically probed by screening a mutation using the chimeric
      receptor Trz. Trz is a hybrid protein between the periplasmic domain of
      chemoreceptor Trg and the cytoplasmic portion of osmosensor EnvZ, which provides
      a system for monitoring the chemotactic interaction of RBP on MacConkey agar
      plates when coupled with a reporter lacZ fused to an ompC gene. The expression of
      ompC can be increased by an interaction of ribose-bound RBP with Trz. A transport
      defect, either in the binding protein or in the membrane permease, causes a
      signalling-constitutive Lac+ phenotype of Trz even in the absence of ribose. This
      appears to be due to the presence of a small amount of ribose, which is normally
      taken up by the high-affinity transport system. By taking advantage of this, we
      have designed a system for genetic screening that permits a selection for
      mutations in the binding protein, causing specific defects in permease
      interaction but not in tactic interaction. Mutant RBPs that were isolated were
      unable to perform normal ribose uptake and to utilize ribose as a carbon source,
      while other functions such as taxis and sugar-binding properties were not
      substantially affected. The mutational changes were repeatedly found in several
      residues of RBP, concentrating on three surface regions and comprising two
      domains of the tertiary structure. We suggest that the two regions, including
      residues 52 and 166, are specifically involved in the permease interaction while
      the third region, including residues 72, 134, and others, recognizes both the
      permease and the chemosensory receptor.

PMID- 8878034
TI  - Effect of the deletion of the sigma 32-dependent promoter (P1) of the Escherichia
      coli topoisomerase I gene on thermotolerance.
AB  - Topoisomerase I and DNA gyrase are the major topoisomerase activities responsible
      for the regulation of DNA supercoiling in the bacterium Escherichia coli. The P1
      promoter of topA has previously been shown to be a delta 32-dependent heat-shock
      promoter. A mutant strain with a deletion of P1 was constructed. This mutant is >
      10-fold more sensitive to heat treatment (52 degrees C) than the wild type. After
      brief treatment at 42 degrees C, wild-type Escherichia coli acquires an enhanced
      resistance to the effects of a subsequent 52 degrees C treatment. This is not the
      case for the P1 deletion mutant, which, and under these conditions, is about 100
      fold less thermotolerant than the wild type. The presence of a plasmid expressing
      topoisomerase I restored the heat-survival level of the mutant to that of the
      wild type. During heat shock, the superhelical density of a plasmid with the heat
      inducible rpoD promoter is increased in the P1 deletion mutant. We also note that
      the pulse-labelling pattern of proteins at 42 C (displayed on SDS-polyacrylamide
      gels) is different in the mutant, and, most notably, the amounts of DnaK and of
      GroEL protein are reduced. A model is proposed in order to unify these
      observations.

PMID- 8878035
TI  - Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug
      resistant strains of Pseudomonas aeruginosa.
AB  - OprJ, overproduced in nfxB multidrug-resistant strains of Pseudomonas aeruginosa,
      and OprK, overproduced in the multidrug-resistant strain K385, were demonstrated
      to be immunologically cross-reactive using an OprJ-specific monoclonal antibody.
      Treatment of the purified proteins with trypsin or chymotrypsin yielded virtually
      indistinguishable digestion patterns, and the N-terminal sequence of two trypsin
      fragments was identical for both proteins, indicating that OprJ and OprK share
      identity. The N-terminal amino acid sequences were used to facilitate cloning of
      the oprJ gene on a 5kbp Kpnl fragment and a 10 kbp BamHl fragment. Nucleotide
      sequencing of portions of these fragments revealed that oprJ was the terminal
      gene in a putative three-gene operon, mexC-mexD-oprJ. The predicted mexC-mexD
      oprJ gene products exhibit homology to the MexA-MexB-OprM components of the
      multidrug-resistance efflux pump of P. aeruginosa (43-46% identity). Consistent
      with an implied role for mexC-mexD-oprJ in drug efflux, the mexC-mexD-oprJ
      hyperexpressing strain K385 showed reduced accumulation of a variety of
      antibiotics as compared with its parent strain, and this drug 'exclusion' was
      abrogated by energy inhibitors. The mexC and oprJ products are putative
      lipoproteins of a molecular mass of 40,707 and 51,742 Da, respectively, while
      mexD was predicted to encode a protein of 111 936 Da. Sequencing upstream of mexC
      revealed the presence of the nfxB gene transcribed divergently from the efflux
      genes. Overproduction of OprJ and the attendant multiple-antibiotic resistance of
      strain K385 was shown to result from a point mutation in nfxB, resulting in a H87
      ->R change in the predicted NfxB polypeptide. OprJ overproduction and multidrug
      resistance in K385 was reversed by the cloned nfxB gene, suggesting that nfxB
      encodes a repressor of mexC-mexD-oprJ expression. Consistent with this, the
      cloned nfxB gene repressed synthesis of a mexC-lacZ fusion in Escherichia coli.
      nfxB also repressed expression of a nfxB-lacZ fusion, indicating that NfxB
      negatively regulates its own expression. These data indicate that the multidrug
      resistance of nfxB strains is due to overexpression of an efflux operon, mexC
      mexD-oprJ, encoding components of a second efflux pump in P. aeruginosa.

PMID- 8878037
TI  - Catabolite repression mediated by the catabolite control protein CcpA in
      Staphylococcus xylosus.
AB  - The gene ccpA encoding the catabolite control protein CcpA of Staphylococcus
      xylosus has been cloned and characterized. The CcpA protein belongs to the
      Lacl/GaiR family of bacterial regulators and is comprised of 329 amino acids,
      with a molecular mass of 36.3 kDa. It shows 56% identity with the CcpA proteins
      of Bacillus subtills and Bacillus megaterium. Inactivation of the ccpA gene in
      the genome of S. xylosus relieved the activities of three enzymes, alpha
      glucosidase, beta-glucuronidase, and beta-galactosidase, from cataboilte
      repression by several carbohydrates. Concomitantly, transcription initiation of
      the maltose-utilization operon malRA, including the alpha-glucosidase gene malA,
      was no longer subject to glucose-specific control. Carbon source-dependent malRA
      regulation was also lost upon deletion of a palindromic sequence in the malRA
      promoter region resembling the catabolite-responsive elements essential for CcpA
      dependent catabolite repression in Bacillus. These results strongly suggest that
      S. xylosus CcpA controls transcription of catabolite-repressible genes and
      operons by binding to catabolite-responsive operators when rapidly metabolizable
      carbohydrates are available. Accordingly, the cloned S. xylosus ccpA gene could
      complement the ccpA mutation in B. subtilis. The ccpA gene of S. xylosus is
      transcribed from two promoters, one of which is subject to autogenous repression
      by CcpA. Autoregulation results in a slight reduction of CcpA protein in glucose
      grown cells. The characterization of the role of CcpA in carbon catabolite
      repression in S. xylosus demonstrates that a regulatory mechanism originally
      detected in Bacillus applies to another Gram-positive bacterium with low GC
      content.

PMID- 8878036
TI  - Interaction of FimB and FimE with the fim switch that controls the phase
      variation of type 1 fimbriae in Escherichia coli K-12.
AB  - The phase variation of type 1 fimbriae in Escherichia coli is associated with the
      site-specific inversion of a short DNA element. Recombination at fim requires
      fimB and fimE, and their products are considered to be the fim recombinases. In
      this study, FimB and FimE were overproduced and extracts containing the proteins
      were shown to (i) bind to and (ii) invert the fim switch in vitro. Phenanthroline
      copper protection of DNA-protein complexes showed that both FimB and FimE bind to
      half-sites that flank, and overlap with, the left and right inverted repeats (IRL
      and IRR, respectively) of the fim switch. Alignment of the four half-sites
      identified a conserved 5'-CA doublet; mutation of these two bases lowers the
      affinity of binding of both FimB and FimE to the inverted repeats, and greatly
      diminishes inversion of the fim switch in vivo. The specificity of the fim
      recombinases observed in vivo (FimB switching in both directions; FimE switching
      from on-to-off only) was maintained in vitro. Furthermore, the different binding
      affinities of FimB and FimE for the various half-site combinations suggests that
      the specificity of FimE could arise, in part, from the low affinity of FimE for
      IRL (off).

PMID- 8878038
TI  - The CII protein of bacteriophage 186 establishes lysogeny by activating a
      promoter upstream of the lysogenic promoter.
AB  - We have shown previously that the cII gene product of the non-lambdoid temperate
      bacteriophage 186 is required for the establishment of lysogeny. We show here
      that CII, a potential helix-turn-helix DNA-binding protein, establishes lysogeny
      by activating a promoter (PE) which spans the apl/cII intergenic region, upstream
      of the lysogenic promoter, PL. The start site of the PE transcript (+1) has been
      mapped by primer extension and we have identified the CII binding determinants at
      PE by DNase I footprinting. CII binds to inverted repeat sequences separated by
      two turns of the helix, with binding half-sites centred at the 38 and -58
      positions of PE. Oligomerisation studies with purified CII protein indicate that
      a CII tetramer may be the species that binds to this site. We also show that PE
      is subject to direct negative feedback by the CI repressor.

PMID- 8878039
TI  - Regulatory inputs for the synthesis of ComK, the competence transcription factor
      of Bacillus subtilis.
AB  - Competence in Bacillus subtilis is expressed post-exponentially in response to
      signals which are interpreted by a complex network of regulatory proteins. This
      network culminates in the transcriptional activation of a set of late-competence
      proteins that mediate DNA binding and uptake during transformation. ComK, a
      protein that binds to competence promoters and appears to activate their
      transcription, is itself synthesized in response to the signal-transduction
      network. ComK is known to be required for the transcription of its own gene. We
      have placed comK under control of the xylose-inducible PxylA promoter and used
      this construct to show that ComK synthesis is sufficient as well as necessary to
      induce competence. We have also confirmed that the Mec proteins act post
      transcriptionally to inactivate ComK, probably by protein-protein interaction. We
      have further demonstrated that ComS is required to generate an upstream signal
      that causes reversal of Mec-induced inactivation of ComK. In addition to ComK
      itself, DegU, AbrB, and SinR are required for comK transcription; mutations in
      their genes are bypassed by PxylA-comK induction, and therefore their products
      appear not to act via the Mec proteins. Overproduction of ComK, in a loss-of
      function mec mutant, is also known to bypass the need for DegU, SinR and AbrB. We
      propose that these proteins enhance the activity of ComK as a positive
      autoregulatory transcription factor, acting as coactivator proteins when ComK is
      present at low concentrations. Finally, we demonstrate that when ComK is
      synthesized from the PxylA promoter and mecA is inactivated by mutation, no
      additional growth-stage-regulated control of competence can be detected.

PMID- 8878040
TI  - A cytochrome c biogenesis gene involved in pyoverdine production in Pseudomonas
      fluorescens ATCC 17400.
AB  - Pseudomonas fluorescens ATCC 17400 produces pyoverdine under iron-limiting
      conditions. A Tn5 mutant, 2G11, produced lower amounts of different pyoverdine
      forms and was unable to grow under iron limitation caused by ethylenediamine-di(o
      hydroxy-phenylacetic acid) (EDDHA) or zinc. This mutant was complemented by a 9.6
      kb HindIII-BamHI DNA fragment that contained eight contiguous open reading frames
      (ORFs cytA to cytH). The proteins possibly encoded by this polycistronic gene
      cluster were all similar to the products of cytochrome c biogenesis genes from,
      amongst others, Rhodobacter capsulatus and Bradyrhizobium japonicum, not only in
      terms of amino acid sequence, but also in the overall hydropathy index of these
      proteins. By TnphoA mutagenesis and site-specific gene replacement it was found
      that the first three ORFs (cytA to cytC) were essential for cytochrome c
      production while only the product of cytA was needed for normal pyoverdine
      production. The presence of a putative haem-binding site in the CytA protein
      (WGSWWVWD) was confirmed. From analysis of a constructed phoA fusion, a
      periplasmic location was found for this motif. The ability of the cytA gene to
      restore both cytochrome c and pyoverdine production suggests the involvement of
      this particular gene both in haem and in pyoverdine transport in P. fluorescens.

PMID- 8878041
TI  - DsbA is required for stability of the type IV pilin of enteropathogenic
      escherichia coli.
AB  - The periplasmic Escherichia coli enzyme DsbA catalyses the efficient formation of
      disulphide linkages in numerous extracytoplasmic proteins. Enteropathogenic E.
      coli, a major cause of infantile diarrhoea worldwide, expresses a type IV fimbria
      known as the bundle-forming pilus that promotes adherence to tissue-culture
      cells. In this study, we report that transposon insertions in the dsbA locus
      abolish adherence and dramatically reduce the level of bundlin, the major
      structural subunit of the pilus encoded by the bfpA locus. Adherence and bundlin
      levels are restored by complementation with the cloned dsbA gene. DsbA has no
      effect on bfpA transcription as measured with bfpA-lacZ fusions. Replacement of
      either cysteine codon 129 or 179 of bfpA with a serine codon results in reduced
      levels of bundlin, similar to the effect of the dsbA mutation. As is the case
      with dsbA mutants, this decreased level of bundlin is not due to decreased
      transcription. The half-life of bundlin as detected by pulse-chase experiments is
      dramatically reduced in a dsbA mutant in comparison to the wild type. The effect
      of DsbA on bundlin oxidation is independent of signal-peptide processing. Thus,
      we demonstrate that the DsbA enzyme is critical for the biogenesis of a type IV
      fimbria because of the essential role of a disulphide bond in the stability of
      the major structural subunit. These data illuminate the early steps in the
      biogenesis of type IV fimbriae by demonstrating that newly synthesized prepilin
      is a transmembrane protein accessible to periplasmic and cytoplasmic processing
      enzymes.

PMID- 8878042
TI  - Interchange of the active and silent S-layer protein genes of Lactobacillus
      acidophilus by inversion of the chromosomal slp segment.
AB  - The most-dominant surface-exposed protein in many bacterial species is the S
      protein. This protein crystallises into a regular monolayer on the outside
      surface of the bacteria: the S-layer. Lactobacillus acidophilus harbours two S
      protein-encoding genes, slpA and slpB, only one of which (slpA) is expressed. In
      this study, we show by polymerase chain reaction (PCR) analysis that slpA and
      slpB are located on a 6 kb chromosomal segment, in opposite or orientations. In a
      small fraction of the bacterial population, this segment is inverted. The
      inversion leads to interchanging of the expressed and silent S-protein-encoding
      genes, and places the formerly silent gene behind the S-promoter which is located
      outside the inverted segment. A 26 bp sequence showing a high degree of
      similarity with the consensus sequence recognized by the Din family of invertases
      is present in the region where recombination occurs. Expression of the slpA gene
      seems to be favoured under laboratory growth conditions because 99.7% of the
      chromosomes of an L. acidophilus ATCC 4356 broth culture had the slpA gene
      present at the slp expression site.

PMID- 8878043
TI  - The FinOP repressor system of plasmid R1: analysis of the antisense RNA control
      of traJ expression and conjugative DNA transfer.
AB  - A key determinant of the frequency of IncF plasmid-mediated DNA transfer between
      enterobacterial cells is the FinOP system. traJ, a positive regulator of the
      transfer (tra) genes is controlled at the post-transcriptional level by two
      negative elements, finP and finO. FinP is a plasmid-specific antisense RNA,
      whereas finO encodes a proteic co-repressor which is not plasmid specific but
      exchangeable among F-like plasmids. We designed a traJ-lacZ test system that
      allowed us to monitor the effects of FinP and various FinP mutants on traJ
      expression. Furthermore, the introduction of finO into the test system enabled us
      to assess the function of FinO in the interaction of FinP with its target, the
      traJ mRNA. In this test system, FinP, expressed from a single-copy plasmid, in
      the absence of FinO, repressed traJ expression six-fold. When expressed from a
      pBR322-derived multicopy plasmid FinP repressed traJ expression approx. 2000
      fold. This result unambiguously demonstrated that FinP is sufficient to repress
      traJ expression in a gene dosage-dependent manner. Mutations of finP creating
      base exchanges either in loop I or loop II of the two stem-loop structures of the
      antisense RNA led to a dramatic decrease in the repressor activity. In a combined
      loop I-loop II mutation the repressor activity was almost completely lost,
      supporting the model that the first critical interaction between the two RNA
      molecules occurs via 'kissing' of both loops of the RNAs. Addition of finO to the
      test system enhanced the repression of traJ expression by FinP by up to two
      orders of magnitude. This effect of FinO on FinP activity in vivo might indicate
      that FinO, in addition to its function as an RNA stabilizer, promotes complex
      formation between the target mRNA and the antisense RNA. Such a function of FinO
      has recently been shown to exist in vitro (van Biesen and Frost (1994) Mol
      Microbiol 14: 427-436).

PMID- 8878044
TI  - A new PrfA-regulated gene of Listeria monocytogenes encoding a small, secreted
      protein which belongs to the family of internalins.
AB  - A mutant of Listeria monocytogenes EGD was constructed that carries an extended
      deletion removing the entire PrfA-regulated gene cluster from plcA to plcB and a
      second deletion inactivating the inlA gene. Upon supplementation of this mutant
      with multiple gene copies of prfA, a protein of 30 kDa was detected in the
      supernatant of the mutant strain. The gene encoding this protein was obtained by
      direct and inverse polymerase chain reaction using oligonucleotide primers that
      were deduced from partial amino acid sequences of the purified 30 kDa protein.
      The amino acid sequence of the gene product revealed a protein of 297 amino acids
      that carried eight repeat units with high homology to those of the two known
      internalin proteins A and B. This secretory protein, termed internalin C, is much
      smaller than InlA or InlB and its complete sequence is related to the two known
      internalins. The gene InlC is transcribed into a monocistronic mRNA from a single
      promoter which shows a typical consensus sequence for PrfA-binding at the
      position -40. In contrast to the transcription of the InlAB operon, which is
      downregulated after shift of an L. monocytogenes EGD culture from brain-heart
      infusion into minimum essential medium (MEM), transcription of inlC is induced in
      MEM like most of the other known PrfA-regulated virulence genes. In addition,
      InlC is strongly transcribed in the cytoplasm of phagocytic J774 cells whereas
      inlA is poorly transcribed under these conditions, suggesting that internalin C
      may play a role in a late stage of L. monocytogenes infection rather than in the
      uptake of L. monocytogenes by non-professional phagocytic cells. An InlC deletion
      mutant shows reduced virulence when tested in an intravenous mouse model, but
      intracellular replication of the mutant in Caco-2 and J774 cells appears to be
      comparable with that of the wild-type strain.

PMID- 8878045
TI  - The alpha subunit of RNA polymerase and transcription antitermination.
AB  - The N gene product of coliphage gamma, with a number of host proteins (Nus
      factors), regulates phage gene expression by modifying RNA polymerase to a form
      that overrides transcription-termination signals. Mutations in host nus genes
      diminish this N-mediated antitermination. Here, we report the isolation and
      characterization of the rpoAD305E mutation, a single amino acid change in the
      carboxy terminal domain (CTD) of the alpha subunit of RNA polymerase, that
      enhances N-mediated antitermination. A deletion of the 3' terminus of rpoA,
      resulting in the expression of an alpha subunit missing the CTD, also enhances N
      mediated antitermination and, similar to rpoAD305E, suppresses the effect of nus
      mutations. Thus, the N-Nus complex may be affected through contacts with the CTD
      of the alpha subunit of RNA polymerase, as is a group of regulatory proteins that
      influences initiation of transcription. What distinguishes our findings on the N
      Nus complex from those of previous studies with transcription proteins is that
      all of the regulators characterized in those studies bind DNA and influence
      transcription initiation; whereas the N-Nus complex binds RNA and affects
      transcription elongation. A screen of some previously identified rpoA mutations
      that influence transcription activators revealed only one other amino acid
      change, L290H, in the CTD of the alpha subunit, that influences antitermination.
      Although our results provide evidence that interactions of the alpha subunit of
      RNA polymerase must be considered in forming models of transcription
      antitermination, they do not provide information as to whether the interactions
      of alpha that ultimately influence antitermination occur during initiation or
      during elongation of transcription.

PMID- 8878046
TI  - Regulation of competence for genetic transformation in Streptococcus pneumoniae
      by an auto-induced peptide pheromone and a two-component regulatory system.
AB  - The regulation of competence for genetic transformation in Streptococcus
      pneumoniae depends on a quorum-sensing system, but the only molecular elements of
      the system whose specific role have been identified are an extracellular peptide
      signal and an ABC-transporter required for its export. Here we show that
      transcription of comC, the gene encoding a predicted 41-residue precursor peptide
      that is thought to be processed and secreted as the 17-residue mature competence
      activator, increased approximately 40-fold above its basal level of expression in
      response to exogenous synthetic activator, consistent with earlier experiments
      indicating that the activator acts autocatalytically. We also describe two new
      genes, comD and comE, that encode members of histidine protein kinase and
      response-regulator families and are linked to comC. Disruption of comE abolished
      both response to synthetic activator peptide and endogenous competence induction.

PMID- 8878047
TI  - Identification of the streptococcal competence-pheromone receptor.
AB  - Competence for genetic transformation in certain species of streptococci has been
      known for many years to be induced by a secreted protease-sensitive pheromone,
      referred to as the competence factor or activator, which acts as a quorum-sensing
      signal to co-ordinate expression of late competence genes. We recently reported
      identification of the pheromone of Streptococcus pneumoniae strain Rx as a small
      unmodified peptide, which was termed competence-stimulating peptide (CSP). By
      identifying the gene (comC) encoding the Rx CSP we were able to show that it is
      synthesized as a precursor peptide containing an N-terminal double-glycine type
      leader. In the present work, we describe two alleles of the corresponding gene
      from Streptococcus gordonii strains Challis and NCTC 7865, which are strains with
      distinct competence pheromones and corresponding specific pheromone reactivities.
      In addition, the nucleic acid sequences of two genes located downstream of comC
      were determined; interestingly, these genes encode a two-component signal
      transduction system. We therefore speculated that their products, a histidine
      kinase (ComD) and its cognate response regulator (ComE), act downstream of the
      CSP in competence regulation. By tracing the CSP specificity of the competence
      response in these strains to strain-specific alleles of comD, we obtained
      evidence demonstrating that the histidine kinase ComD is the competence-pheromone
      receptor.

PMID- 8878049
TI  - On the misuse of the term 'lysozyme'.

PMID- 8878048
TI  - New components of protein folding in extracytoplasmic compartments of Escherichia
      coli SurA, FkpA and Skp/OmpH.
AB  - A global search for extracytoplasmic folding catalysts in Escherichia coli was
      undertaken using different genetic systems that produce unstable or misfolded
      proteins in the periplasm. The extent of misfolding was monitored by the
      increased activity of the sigma E regulon that is specifically induced by
      misfolded proteins in the periplasm. Using multicopy libraries, we cloned two
      genes, surA and fkpA, that decreased the sigma E-dependent response
      constitutively induced by misfolded proteins. According to their sequences and
      their biochemical activities, SurA and FkpA belong to two different peptidyl
      prolyl isomerase (PPI) families. Interestingly, surA was also selected as a
      multicopy suppressor of a defined htrM (rfaD) null mutation. Such mutants produce
      a defective lipopolysaccharide that is unable to protect outer membrane proteins
      from degradation during folding. The SurA multicopy suppression effect in htrM
      (rfaD) mutant bacteria was directly associated with its ability to catalyse the
      folding of outer membrane proteins immediately after export. Finally, Tn10
      insertions were isolated, which led to an increased activity of the sigma E
      regulon. Such insertions were mapped to the dsb genes encoding catalysts of the
      protein disulphide isomerase (PDI) family, as well as to the surA, fkpA and
      ompH/skp genes. We propose that these three proteins (SurA, FkpA and OmpH/Skp)
      play an active role either as folding catalysts or as chaperones in
      extracytoplasmic compartments.

PMID- 8878050
TI  - ATP-sensitive K+ channels in the kidney.
AB  - ATP-sensitive K+ channels (KATP channels) form a link between the metabolic state
      of the cell and the permeability of the cell membrane for K+ which, in turn, is a
      major determinant of cell membrane potential. KATP channels are found in many
      different cell types. Their regulation by ATP and other nucleotides and their
      modulation by other cellular factors such as pH and kinase activity varies widely
      and is fine-tuned for the function that these channels have to fulfill. In most
      excitable tissues they are closed and open when cell metabolism is impaired;
      thereby the cell is clamped in the resting state which saves ATP and helps to
      preserve the structural integrity of the cell. There are, however, notable
      exceptions from this rule; in pancreatic beta-cells, certain neurons and some
      vascular beds, these channels are open during the normal functioning of the cell.
      In the renal tubular system, KATP channels are found in the proximal tubule, the
      thick ascending limb of Henle's loop and the cortical collecting duct. Under
      physiological conditions, these channels have a high open probability and play an
      important role in the reabsorption of electrolytes and solutes as well as in K+
      homeostasis. The physiological role of their nucleotide sensitivity is not
      entirely clear; one consequence is the coupling of channel activity to the
      activity of the Na-K-ATPase (pump-leak coupling), resulting in coordinated
      vectorial transport. In ischemia, however, the reduced ATP/ADP ratio would
      increase the open probability of the KATP channels independently from pump
      activity; this is particularly dangerous in the proximal tubule, where 60 to 70%
      of the glomerular ultrafiltrate is reabsorbed. The pharmacology of KATP channels
      is well developed including the sulphonylureas as standard blockers and the
      structurally heterogeneous family of channel openers. Blockers and openers,
      exemplified by glibenclamide and levcromakalim, show a wide spectrum of
      affinities towards the different types of KATP channels. Recent cloning efforts
      have solved the mystery about the structure of the channel: the KATP channels in
      the pancreatic beta-cell and in the principal cell of the renal cortical
      collecting duct are heteromultimers, composed of an inwardly rectifying K+
      channel and sulphonylurea binding subunit(s) with unknown stoichiometry. The
      proteins making up the KATP channel in these two cell types are different (though
      homologous), explaining the physiological and pharmacological differences between
      these channel subtypes.

PMID- 8878052
TI  - Differences in ligand binding profiles between cloned rabbit and human 5-HT1D
      alpha and 5-HT1D beta receptors: ketanserin and methiothepin distinguish rabbit 5
      HT1D receptor subtypes.
AB  - The study of serotonin receptor function has been complicated by the extreme
      molecular diversity of serotonin receptor subtypes, the lack of selective
      agonists and antagonists for many of the subtypes, and divergence in the
      pharmacological properties of a single receptor subtype across different animal
      species. An example of this pharmacological diversity between species homologues
      is provided by the 5-HT1D receptor subfamily. To further advance the ability to
      characterize and pharmacologically compare functional responses mediated by
      native 5-HT1D receptors, we have cloned the 5-HT1D alpha and 5-HT1D beta receptor
      subtypes from the rabbit and evaluated their pharmacological profiles using
      radioligand binding assays. The deduced amino acid sequences of the rabbit 5-HT1D
      alpha and 5-HT1D beta receptor genes displayed 60% overall identity [75%
      transmembrane (TM) identity] to each other and > 90% overall identity (95% TM
      identity) to their corresponding human homologues. Two compounds were identified
      in binding assays which discriminated between the closely-related 5-HT1D
      receptors. Ketanserin exhibited high affinity (pKi = 7.66) and selectivity (> 20
      fold) for the 5-HT1D alpha receptor while methiothepin displayed high affinity
      (pKi = 7.86) and selectivity (16-fold) for the 5-HT1D beta receptor subtype. The
      rabbit and human recombinant 5-HT1D receptors showed significant intraspecies
      (rabbit 5-HT1D alpha vs. 5-HT1D beta) and interspecies (i.e. rabbit vs. human 5
      HT1D alpha) similarities in their ligand binding profiles. These data suggest
      that 5-HT1D-mediated responses in rabbit preparations may provide information
      relevant to the pharmacology of the 5-HT1D receptor subtypes in humans.

PMID- 8878051
TI  - Pharmacological characterizations of recombinant human 5-HT1D alpha and 5-HT1D
      beta receptor subtypes coupled to adenylate cyclase inhibition in clonal cell
      lines: apparent differences in drug intrinsic efficacies between human 5-HT1D
      subtypes.
AB  - Recombinant human 5-HT1D alpha and 5-HT1D beta receptor subtypes were stably
      expressed in NIH-3T3 fibroblasts (1D alpha cell line) and Y-1 adrenocortical
      tumor cells (1D beta cell line), respectively, for pharmacological evaluations of
      serotonergic compounds to inhibit forskolin-stimulated cAMP accumulation (FSCA).
      [3H]LSD saturation studies indicated that 5-HT1D receptor expression levels were
      slightly higher in the 1D beta cell line (Bmax = 1334 +/- 134 fmol/mg protein)
      than in the 1D alpha cell line (Bmax = 900 +/- 218 fmol/mg protein). 5-HT
      inhibited FSCA with similar potencies (EC50 approximately 2 nM) in both assay
      systems. The rank order of agonist potencies in both clonal cell lines matched
      their pharmacological profiles previously determined in binding studies:
      dihydroergotamine > or = 5-carboxamidotryptamine (5-CT) > LSD > or = 5-HT >
      sumatriptan > 1-naphthylpiperazine (1-NP) > yohimbine > 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH DPAT) > 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (DOI), with Ki/EC50 ratios greater than unity. Methiothepin acted as a silent
      antagonist at both human 5-HT1D alpha and 5-HT1D beta receptors with apparent
      dissociation constants (Kb values) of 12 +/- 1 nM and 3 +/- 1 nM, respectively.
      Whereas GR 127,935, metergoline, DOI, and quipazine acted as full agonists in the
      1D alpha cell line, these compounds behaved as partial agonists in the 1D beta
      cell line. To determine whether high levels of receptor reserve might mask
      partial agonist activity in the two second messenger assay systems, studies were
      performed using the irreversible receptor alkylating agent N-ethoxycarbonyl-2
      ethoxy-1,2-dihydroquinoline (EEDQ). The relationships between receptor occupancy
      and inhibition of FSCA were determined for 5-HT, sumatriptan, and 1-NP in both
      clonal cell lines after partial receptor inactivation using Furchgott analysis.
      Hyperbolic relationships between receptor occupancy and second messenger response
      were determined for 5-HT in both transfected cell lines. Steep hyperbolic
      relationships were also found for sumatriptan and 1-NP in the 1D beta cell line
      whereas nearly linear relationships were observed for these two compounds in the
      1D alpha cell line. Moreover, KA/EC50 ratios of these compounds were
      significantly larger in the 1D beta (10-32) as compared to the 1D alpha (0.9-2.5)
      cell line. These data are consistent with the hypothesis that the two
      heterologous expression systems contain a differential amount of receptor
      reserve. Despite the presence of an apparently larger-receptor reserve in the 1D
      beta cell line, GR 127,935, metergoline, DOI, and quipazine behaved as partial
      agonists. Although the potencies (EC50 values) of compounds matched their
      respective affinity constants (Ki values) for the closely-related 5-HT1D
      subtypes, differences in intrinsic activities were observed for a few compounds
      between the two 5-HT1D receptor expression systems. Since receptor reserve is
      dependent on the properties of both the assay system and drug, the observed
      variations in intrinsic activity, although influenced by the variable amounts of
      receptor reserve in the two transfected cell lines, reflect primarily system
      independent differences in the intrinsic efficacy of the tested compounds at the
      two human 5-HT1D receptors. Higher intrinsic efficacies of compounds at the human
      5-HT1D alpha receptor relative to the human 5-HT1D beta subtype may be
      responsible for the higher intrinsic activities observed in the 1D alpha cell
      line, even though receptor reserve is apparently lower in this system.

PMID- 8878053
TI  - Inhibition of 5-HT3 receptor function by imidazolines in mouse neuroblastoma
      cells: potential involvement of sigma 2 binding sites.
AB  - The influence of several imidazolines and sigma-site ligands on cation influx
      through the 5-HT3 receptor channel in N1E-115 mouse neuroblastoma cells was
      studied by measuring the 2-min influx of the organic cation [14C] guanidinium
      induced by 1 microM 5-HT (in the presence of 10 microM substance P in all
      experiments). In addition, we determined specific binding of [3H]DTG (1,3-di(2
      tolyl)-guanidine), a selective sigma-site radioligand, and [3H] GR65630 (3-(5
      methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1- propanone), a selective 5
      HT3 receptor antagonist, to membranes prepared from N1E-115 cells. The 5-HT
      induced [14C]guanidinium influx was inhibited by the imidazolines, ondansetron,
      antazoline, idazoxan, BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline),
      cirazoline, naphazoline, clonidine and by the guanidine agmatine, but not by the
      catecholamine adrenaline. The inhibitory effect of the imidazolines on cation
      influx through the 5-HT3 receptor channel was mimicked by the sigma-site ligands,
      (+/-)-ifenprodil, (+)-3-PPP ((R)-3-(3-hydroxyphenyl)-N-propylpiperidine), DTG
      (1,3-di-tolyl-guanidine). haloperidol, dizocilpine, and ketamine as well as by
      the polyamines, arcaine and spermidine.-Ondansetron inhibited [3H]GR65630 binding
      with high affinity, whereas inhibition of binding of this radioligand to the 5
      HT3 receptor by antazoline, BDF 6143, idazoxan, cirazoline, (+/-)-ifenprodil, (+)
      3-PPP, DTG and haloperidol occurred in the high micromolar range. In the
      competition experiments with [3H]DTG, (+/-)-ifenprodil, haloperidol, unlabelled
      DTG, BDF 6143 and (+)-3-PPP inhibited binding of the radioligand at moderate
      affinity (Ki values in the range of 1 microM or lower), whereas ondansetron,
      antazoline, idazoxan, cirazoline, naphazoline, clonidine, tolazoline, efaroxan,
      RX821002 (2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazoline), ketamine and
      spermidine exhibited affinity, in the high micromolar or millimolar range only.
      Comparison of the potencies of the ligands (pIC50% values) in inhibiting 5-HT
      induced [14C]guanidinium influx with their affinities (pKi values) at the 5-HT
      recognition sites of the 5-HT3 receptor and at the sigma 2-sites of the N1E-115
      cells by means of multiple regression analysis revealed a significant correlation
      with the affinities at both sites. In conclusion, our data suggest that
      imidazolines and sigma-ligands, which as a rule possess low affinity for the 5-HT
      recognition site of the 5-HT3 receptor, may be assumed to exert their inhibitory
      effect on cation influx through the 5-HT3 receptor channels, at least in part, by
      interacting with sigma 2-binding sites.

PMID- 8878054
TI  - Presynaptic alpha 2-autoreceptors in mouse heart atria: evidence for the alpha 2D
      subtype.
AB  - Presynaptic alpha 2-autoreceptors in mouse atria were characterized in terms of
      the alpha 2A, alpha 2B, alpha 2C and alpha 2D subtypes. Segments of the atria
      were preincubated with 3H-noradrenaline and then superfused and stimulated
      electrically. The affinity of up to 16 antagonists for the autoreceptors was
      assessed as (1) pEC30% values. i.e. concentrations that increased previously
      autoinhibited release of 3H-noradrenaline (120 pulses, 3 Hz) by 30%, and (2) pKd
      values against the release-inhibiting effect of 5-bromo-6-(2-imidazolin-2
      ylamino)-quinoxaline (UK 14,304) under conditions of no or little autoinhibition
      (2 trains of 20 pulses, 50 Hz, train interval 120 s). The pKd values correlated
      well with the pEC30% values (r = 0.98; P < 0.001; slope of regression line 0.93),
      indicating that UK 14,304 and released noradrenaline modulated the release of
      noradrenaline through pharmacologically identical receptors. Comparison with
      antagonist affinities for (1) prototypic native alpha 2 radioligand binding
      sites, (2) radioligand binding sites in COS cells transfected with alpha 2
      subtype genes, and (3) previously classified presynaptic alpha 2-autoreceptors
      all taken from the literature-indicated that the mouse atrial autoreceptors
      corresponded to the alpha 2D subtype. For example, the pKd values at mouse atrial
      auto-receptors correlated closely with pKd values at native alpha 2D binding
      sites in the bovine pineal gland (r = 0.96; P < 0.001); with pKd values at alpha
      2D binding sites in COS cells transfected with the rat alpha 2D gene (r = 0.85; P
      < 0.01); and with pKd values at guinea-pig cerebral and atrial and mouse cerebral
      alpha 2D-autoreceptors (r = 0.96-0.98; P < 0.001). The antagonist pKd values at
      mouse atrial autoreceptors correlated less with pKd values at alpha 2A, alpha 2B
      and alpha 2C sites. It is concluded that the presynaptic alpha 2-autoreceptors in
      mouse atria are alpha 2D. This identification supports the hypothesis that at
      least the majority of alpha 2-autoreceptors belong to the alpha 2A/D pair of
      orthologous alpha 2-adrenoceptors.

PMID- 8878055
TI  - Adenosine A2A receptors mediate the inhibitory effect of adenosine on formyl-Met
      Leu-Phe-stimulated respiratory burst in neutrophil leucocytes.
AB  - Using the reverse transcription polymerase chain reaction (RT-PCR) we found that
      human neutrophils express mRNA for both A2A and A2B adenosine receptors, and
      using selective adenosine receptor agonists and antagonists we have characterized
      the type of adenosine receptor mediating inhibition of formyl-Met-Leu-Phe (fMLP)
      induced oxidative burst. The order of potency of agonists was 5'-N-ethyl
      carboxamidoadenosine (NECA) > 2-phenylaminoadenosine > 2-[p-(2-carbonyl-ethyl)
      phenyl-ethylamino]-5'-N-ethyl-carboxamido adenosine (CGS 21680) > adenosine > N6
      cyclopentyl-adenosine. This agrees with the agonist potency at human A2A
      receptors. The effect of adenosine was antagonized by 30 microM theophylline >
      caffeine = paraxanthine, i.e. concentrations close to those occurring in plasma
      after consumption of caffeine-containing beverages. The effect of NECA was
      unaltered by the A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine, but
      inhibited by the A2A receptor selective antagonists 4-amino-8-chloro-1-phenyl
      [1,2,4]-triazolo[4,3-a]quinoxaline (CP 66,713), 1,3-dipropyl-8-(3,4
      dimethoxystyryl) -7-methylxanthine (KF 17387) and 8-(3-chlorostyryl)caffeine as
      well as by the non-selective, non-xanthine antagonist 5-amino-9-chloro-2-(2
      furyl)-[1,2,4]-triazolo-[1,5-c]quinazoline methane sulphonate (CGS 15943). The
      adenosine receptor mediated responses were antagonized by the protein kinase A
      blocker Rp-cyclic adenosine 3',5'-phosphorothioate (Rp-cAMP). In conclusion, the
      adenosine-induced inhibition of neutrophil activation is mediated by adenosine
      A2A receptors.

PMID- 8878057
TI  - The role of extraneuronal amine transport systems for the removal of
      extracellular catecholamines in the rabbit.
AB  - As selective inhibitors of the extraneuronal monoamine uptake system (uptake2)
      suitable for in-vivo studies were not available, the question of whether uptake2
      plays a definite role in vivo is largely unresolved. We attempted to resolve the
      question by using 1,1'-diisopropyl-2,4'-cyanine iodide (disprocynium24), a novel
      agent that blocks uptake2 in vitro with high potency. Anaesthetized rabbits were
      infused with 3H-labelled noradrenaline, adrenaline and dopamine, and
      catecholamine plasma clearances as well as rates of spillover of endogenous
      catecholamines into plasma were measured before and during treatment with either
      disprocynium24 or vehicle. Four groups of animals were studied: group I, no
      further treatment: group II, monoamine oxidase (MAO) and catechol-O
      methyltransferase (COMT) inhibited; group III, neuronal uptake (uptake1)
      inhibited; group IV, uptake1 as well as MAO and COMT inhibited. Disprocynium24
      (270 nmol kg-1 i.v. followed by an i.v. infusion of 80 nmol kg-1 min-1) did not
      alter heart rate and mean arterial blood pressure, but increased cardiac output
      by 22% and decreased the total peripheral vascular resistance by 16% with no
      difference between groups. When compared with vehicle controls, catecholamine
      clearances (normalized for the cardiac output of plasma) were decreased and
      spillover rates increased in response to disprocynium24. Although there were
      statistically significant between-group differences in baseline clearances (which
      decreased in the order: group I > group II > group III > group IV), the drug
      induced clearance reductions relative to vehicle controls were similar in groups
      I to IV and amounted to 29-38% for noradrenaline, 22-31% for adrenaline and 16
      22% for dopamine. Hence, there was still a significant % reduction in
      catecholamine clearances even after the combined inhibition of MAO and COMT, and
      there was no increase in the % reduction of clearances after inhibition of
      uptake1. Noradrenaline spillover increased in response to disprocynium24 in all
      four groups by 1.6- to 1.9-fold, whereas a 1.5- to 2.0-fold increase in
      adrenaline and dopamine spillover was observed in groups II and IV only. The
      results indicate that disprocynium24 interferes with the removal of circulating
      catecholamines not only by inhibiting uptake2, but also by inhibiting related
      organic cation transporters. As disprocynium24 increased the spillover of
      endogenous catecholamines into plasma even after inhibition of MAO and COMT,
      organic cation transporters may also be involved in the removal of endogenous
      catecholamines before they enter the circulation.

PMID- 8878056
TI  - Pharmacokinetic and alpha 1-adrenoceptor antagonistic properties of two cyanine
      type inhibitors of extraneuronal monoamine transport.
AB  - 1,1'-Diethyl-2,2'-cyanine (decynium22) and 1,1'-diisopropyl-2,4'-cyanine
      (disprocynium24) are highly potent inhibitors of the extraneuronal monamine
      transporter. When given as i.v. bolus injections (4 mumol kg-1) to anaesthetized
      rabbits, both drugs elicited a transient fall in blood pressure without altering
      heart rate. The observed maximum fall in diastolic blood pressure was 59% after
      decynium22 and 43% after disprocynium24 administration. The pharmacokinetics of
      decynium22 and disprocynium24 were similar; they were characterized by short half
      lives for elimination (8.2 and 4.5 min, respectively) and very high plasma
      clearances (173 and 180 ml kg-1 min-1, respectively). The mechanism underlying
      the blood pressure-lowering effect of decynium22 was explored in the isolated
      incubated rabbit aorta. Decynium22 antagonized the noradrenaline-induced
      contraction; the pA2 for this interaction was 7.6, and the slope of the
      corresponding Schild plot was unity. In a membrane preparation from rat
      myocardium, decynium22 as well as disprocynium24 inhibited the specific binding
      of [125I]-2-[beta-(4-hydroxy-3-iodophenyl)-ethylaminomethyl]- tetralone (125I
      HEAT), a selective ligand to alpha 1-adrenoceptors. The Ki's were 5.3 and 240
      mumol l-1 for decynium22 and disprocynium24, respectively. The type of binding
      inhibition by decynium22 was competitive. It is concluded that the two inhibitors
      of extraneuronal monoamine transport decynium22 and disprocynium24 lower blood
      pressure by blocking alpha 1-adrenoceptors. A comparison of their potencies in
      blocking extraneuronal monoamine transport and alpha 1-adrenoceptors clearly
      indicates that disprocynium24 is more suitable for studies designed to determine
      the role of extraneuronal monoamine transport in vivo. Considering its very fast
      elimination kinetics, disprocynium24 must be administered by constant rate
      infusions in order to avoid large fluctuations of plasma levels.

PMID- 8878058
TI  - Disprocynium24, a novel inhibitor of the extraneuronal monoamine transporter, has
      potent effects on the inactivation of circulating noradrenaline and adrenaline in
      conscious rat.
AB  - The role of extraneuronal uptake in terminating the actions of catecholamines has
      been difficult to evaluate in vivo, largely because of lack of suitable
      inhibitors. The compound, 1,1'-diisopropyl-2,4'-cyanine iodide or disprocynium24
      (D24), is a novel inhibitor of extraneuronal uptake with a high degree of potency
      in vitro. This study examined the actions of D24 on the inactivation and
      metabolism of circulating noradrenaline and adrenaline in conscious rats. Animals
      received i.v. infusions of 3H-labelled noradrenaline and adrenaline, and their
      extraneuronal O-methylated metabolites, normetanephrine and metanephrine. Plasma
      concentrations of endogeneous and 3H-labelled catecholamines and metanephrines
      were measured before and after D24. D24 caused large increases in plasma
      concentrations of noradrenaline and adrenaline, effects due to both decreases in
      their plasma clearances and increases in their rates of release into plasma.
      Plasma concentrations of normetanephrine and metanephrine also increased due to
      their decreased clearance from plasma. Increased release of normetanephrine into
      plasma did not contribute to increased plasma concentrations of normetanephrine.
      In fact, the contribution of extraneuronal O-methylation to noradrenaline
      clearance decreased substantially after D24. The data indicate that D24 is a
      potent inhibitor of the extraneuronal catecholamine transporter in vivo and that
      this process contributes importantly to the removal of circulating catecholamines
      and their O-methylated amine metabolites. Increased release of noradrenaline into
      plasma may reflect an increase in the proportion of transmitter that escapes from
      sites of release into the circulation. However, increased adrenaline release
      indicates that the drug also causes sympathoadrenal activation.

PMID- 8878060
TI  - Inward transport of 3H-MPP+ in freshly isolated rat hepatocytes: evidence for
      interaction with catecholamines.
AB  - 1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP), is efficiently taken up and accumulated
      by rat hepatocytes. However, the nature of the mechanism(s) involved in the
      hepatic uptake of MPP+ remains partially unknown. The aim of the present study
      was to further characterize the hepatic uptake of 3H-MPP+, namely by
      investigating the interactions of catecholamines (which are also efficiently
      taken up by rat hepatocytes) with MPP+ transport. The accumulation of 3H-MPP+ in
      isolated rat hepatocytes occurred through saturable and non-saturable mechanisms.
      The kinetics of the saturable component of 3H-MPP+ uptake was as follows: Vmax =
      181.3 +/- 11.1 pmol mg protein-1 min-1 and Km = 47.1 microM (27.9, 66.3) (n = 5).
      The diffusion constant (in ml mg protein-1 min-1) for the non-saturable uptake of
      3H-MPP+ was 0.00068 (0.00052, 0.00083) (n = 5). From the analysis of the time
      course of 3H-MPP+ accumulation at a substrate concentration of 100 nM 3H-MPP+, it
      was found that the rate constant of inward transport of 3H-MPP+ into hepatocytes
      (k(in)) was 15.7 +/- 3.8 microliters mg protein-1 min-1, the rate constant of
      outward transport of 3H-MPP+ from hepatocytes (kout) was 0.077 +/- 0.023 min-1
      and the equilibrium accumulation (Amax) of 3H-MPP+ was 20.2 +/- 2.0 pmol mg
      protein-1 (n = 36). Decynium22 (1,1'-diethyl-2,2'-cyanide; 1 microM)
      significantly reduced kin to 6.1 +/- 1.8 microliters mg protein-1 min-1 (P <
      0.05) and the equilibrium accumulation (Amax) of 3H-MPP+ to 9.6 +/- 1.3 pmol mg
      protein-1 (P < 0.005) (n = 36). 3H-MPP+ accumulation (in cells incubated with 200
      nM 3H-MPP+) was sensitive to (-)-adrenaline, (-)-isoprenaline, (-)-dopamine, (+/
      )-adrenaline and (-)-noradrenaline. The most potent catecholamine in inhibiting
      3H-MPP+ uptake was (-)-adrenaline, with an IC50 of 99 (22, 449) microM (n = 6). (
      )-Adrenaline competitively inhibited 3H-MPP+ uptake, as it significantly
      increased the Km value of 3H-MPP+ uptake (to 125.4 microM (63.6; 187.1); P <
      0.02; n = 3) but did not change the Vmax value. The cyanine-derivatives
      decynium22 and cyanine863 (1-ethyl-2-([1,4-dimethyl-2-phenyl-6-pyrimidinylidene]
      methyl)quinolinium), which inhibit uptake2 as well as the apical type of the
      renal transporter for organic cations, potently inhibited 3H-MPP+ uptake with
      IC50's of 1.4 (0.4-5.3) (n = 6) and 6.5 (2.6-16) (n = 4) microM, respectively.
      Under conditions of monoamine oxidase (MAO) and catechol-O-methyl transferase
      (COMT) inhibition (with either pargyline (500 microM) + Ro01-2812 (3,5
      dinitropyrocatechol; 2 microM) or pargyline (500 microM) + U-0521 (3,4-dihidroxy
      2-methyl-propiophenone; 12 microM)), (-)-adrenaline (up to 1 mM) had no
      inhibitory effect on the uptake of 3H-MPP+. Moreover, the uptake of 3H-MPP+ in
      the presence of pargyline + Ro 01-2812 was significantly lower (66.9 +/- 30.4%; P
      < 0.05; n = 4) than in the absence of these compounds. Therefore, the effect of
      these MAO and COMT inhibitors on 3H-MPP+ uptake was examined. Interestingly
      enough, pargyline, Ro 01-2812 and U-0521 were found to inhibit the uptake of 3H
      MPP+ (in cells incubated with 200 nM 3H-MPP+): 500 microM pargyline, 2 microM Ro
      01-2812 and 100 microM U-0521 decreased the accumulation of 3H-MPP+ to 38.1 +/-
      6.8 (n = 5), 60.5 +/- 10.1 (n = 7) and 71.3 +/- 14.5 (n = 7) % of control,
      respectively. It is concluded that 3H-MPP+ is efficiently taken up by rat
      hepatocytes by a carrier-mediated mechanism sensitive to catecholamines,
      decynium22 and cyanane863, and to the enzyme inhibitors pargyline, Ro 01-2812 and
      U-0521.

PMID- 8878059
TI  - Translocation of dopamine and binding of WIN 35,428 measured under identical
      conditions in cells expressing the cloned human dopamine transporter.
AB  - Translocation of [3H]dopamine and binding of [3H]WIN 35,428 were measured in
      intact C6 glioma cells expressing the cloned human dopamine transporter (hDAT)
      under identical conditions of assay buffer (phosphate-Krebs) and temperature (25
      degrees C) with uptake at initial velocity and binding at equilibrium. In the
      intact cells, [3H]dopamine uptake was a one-component process; in contrast,
      [3H]WIN 35,428 binding included both a high-affinity component, inhibitable by
      micromolar concentrations of dopamine, and a low-affinity component only
      partially inhibited by millimolar concentrations of dopamine. Binding (high
      affinity) over uptake Ki ratios were on the average 2.3 for the inhibitors WIN
      35,428, cocaine, GBR 12909, and BTCP. The potency of dopamine in inhibiting its
      own translocation was close to that in inhibiting [3H]WIN 35,428 binding
      consonant with a more rapid reorientation step of the DAT in the C6-hDAT system
      than in rat striatal synaptosomes. The similarity in turnover values of the DAT
      estimated in the current experiments with the C6-hDAT system and in our previous
      study on rat striatal synaptosomes, performed under comparable conditions,
      suggest that all DAT's inserted into the C6 cell membrane are functionally
      active.

PMID- 8878061
TI  - Both ethanol and ifenprodil inhibit NMDA-evoked release of various
      neurotransmitters at different, yet proportional potency: potential relation to
      NMDA receptor subunit composition.
AB  - Superfused slices of the rat cerebral cortex and corpus striatum were used to
      investigate the effect of ethanol on the N-methyl-D-aspartate (NMDA)-evoked
      release of various [3H]neurotransmitters. To obtain information on the subunit
      composition of the NMDA receptors involved, the influence of ifenprodil (a drug
      which preferentially inhibits NMDA receptors containing the NMDAR2B subunit) on
      the NMDA-evoked [3H]neurotransmitter release was also determined. Ethanol
      inhibited the NMDA-evoked release of all neurotransmitters investigated in a
      concentration-dependent manner. Irrespective of the brain region, ethanol was 2.6
      5.1 times more potent in inhibiting the release of [3H]noradrenaline, [3H]5
      hydroxytryptamine and [3H]GABA than the release of [3H]acetylcholine and
      [3H]dopamine. Ifenprodil inhibited the NMDA-evoked release of these
      [3H]neurotransmitters in both brain regions at virtually the same potency order
      as ethanol. Comparison of the potencies of ethanol and ifenprodil in inhibiting
      NMDA-evoked [3H]neurotransmitter release revealed an excellent correlation (r =
      0.96; P < 0.001). After blockade of the highly ifenprodil-sensitive fraction of
      the NMDA receptors by 100 nM ifenprodil, the potency of ethanol in inhibiting
      NMDA-evoked [3H]noradrenaline release in the cerebral cortex was decreased by a
      factor of 6. In contrast, 100 nM ifenprodil did not affect the potency of ethanol
      in inhibiting [3H]dopamine and [3H]acetylcholine release in the corpus striatum.
      It is concluded that ethanol predominantly inhibits NMDA receptors containing a
      high proportion of the NMDAR2B subunit (as reflected by high sensitivity to
      ifenprodil), i.e. the NMDA receptors involved in stimulation of noradrenaline, 5
      hydroxytryptamine and GABA release. In view of the ability of ifenprodil to
      interact with ethanol at NMDA receptors, which are important sites of action of
      ethanol, ifenprodil may be assumed to influence neuronal effects of ethanol in
      vivo.

PMID- 8878062
TI  - Transport of small organic cations in the rat liver. The role of the organic
      cation transporter OCT1.
AB  - The kidneys and the liver are the principal organs for the inactivation of
      circulating organic cations. Recently, an organic cation transporter (OCT1) has
      been cloned from rat kidney. In order to answer the question whether OCT1 is
      involved also in hepatic uptake of organic cations, the pharmacological
      characteristics of organic cation transport in hepatocytes were compared to the
      characteristics of transiently expressed OCT1. Primary cultures of rat
      hepatocytes avidly accumulated the small organic cation 3H-1-methyl-4
      phenylpyridinium (3H-MPP+). At equilibrium, the hepatocytes accumulated 3H-MPP+
      56-fold. Initial rates of specific 3H-MPP+ transport in hepatocytes were
      saturable. The half-saturating concentration was 13 mumol/l. 3H-MPP+ transport
      was sensitive to quinine (Ki = 0.79 mumol/l) and cyanine863 (Ki = 0.097 mumol/l).
      Quinine and cyanine863 are known inhibitors of type I hepatic transport of
      cationic drugs and of renal excretion of organic cations, respectively. To
      compare the functional characteristics of 3H-MPP+ transport in hepatocytes with
      those of OCT1, OCT1 has been heterologously expressed and characterized in a
      mammalian cell line (293 cells). Initial rates of 3H-MPP+ transport were
      saturable, the Km being 13 mumol/l. The rank order of inhibitory potencies of
      various inhibitors was almost identical in hepatocytes and 293 cells transiently
      transfected with OCT1. There was a positive correlation between the Ki's for the
      inhibition of 3H-MPP+ transport in isolated hepatocytes and transfected 293 cells
      (r = 0.85; P < 0.01; n = 8). The results indicate that OCT1 is functionally
      expressed not only in the kidney but also in hepatocytes where it is responsible
      for the transport of small organic cations which, in the past, have been
      classified as type I substrates.

PMID- 8878064
TI  - Effects of potassium channel inhibitors on nitrergic and adrenergic
      neurotransmission in lamina propria of the female rabbit urethra.
AB  - Electrical field stimulation of strip preparations of the female rabbit urethral
      lamina propria induces a frequency-dependent adrenergic contraction or a non
      adrenergic, non-cholinergic (NANC) relaxation, mediated by nitric oxide,
      depending on the prevailing tension. To study the role of potassium channels in
      these responses, the effects of inhibitors of voltage-dependent (dendrotoxin I, 4
      aminopyridine), low (apamin) and high (iberiotoxin, charybdotoxin) conductance
      calcium-activated and ATP-sensitive (glibenclamide) potassium channels on the
      frequency-response relationship were examined. 4-Aminopyridine (1 mM), but none
      of the other inhibitors, augmented the NANC relaxation. The maximal response was,
      however, unaffected by 4-aminopyridine. The adrenergic contraction was enhanced
      by 4-aminopyridine (1 mM), dendrotoxin I (0.1 microM), iberiotoxin (0.1 microM)
      and charybdotoxin (0.1 microM), but not by apamin (0.1 microM) and glibenclamide
      (10 microM). Besides reducing the frequency eliciting half maximal contraction
      dendrotoxin and charybdotoxin also enhanced the maximal response. None of the
      inhibitors affected the relaxation induced by the nitric oxide donor 3
      morpholinosydnonimine or the contraction elicited by noradrenaline. The results
      suggest that dendrotoxin-sensitive voltage-dependent and high conductance calcium
      activated neuronal potassium channels participate in adrenergic, but not in
      nitrergic, neurotransmission in the lamina propria of the female rabbit urethra.
      This offers a possibility to selectively interfere with the adrenergic
      neuroeffector system with drugs acting on these K-channels.

PMID- 8878063
TI  - Tachykinin receptors mediate atropine-resistant rat duodenal reflex contractions
      in vivo.
AB  - The study aimed to establish the possible role of tachykinins as mediators of
      atropine-resistant reflex contractions evoked by balloon distension in the
      proximal duodenum of urethane-anesthetized, guanethidine (34 mumol/kg s.c.)
      pretreated rats. Distension of the balloon with a small amount (0.2-0.3 ml) of
      saline induced the appearance of phasic rhythmic contractions (about 11 mmHg in
      amplitude) which were promptly suppressed by either atropine (3 mumol/kg i.v.) or
      hexamethonium (28 mumol/kg i.v.). Despite the continuous i.v. infusion of
      atropine (2 mumol/h), low-amplitude rhythmic phasic contractions recovered, which
      were promptly suppressed by hexamethonium, to indicate the involvement of an
      atropine-resistant excitatory reflex. The amplitude of these atropine-resistant
      contractions was increased to about 4-5 mmHg by further distension of the balloon
      (0.4-0.6 ml) : under these conditions, the atropine-resistant contractions
      undergo a progressive fading. The fading was prevented by i.v. administration of
      the nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME,
      55 mumol/h), to provide a suitable baseline (amplitude of contractions was 7-8
      mmHg) for studying the effect of tachykinin receptor antagonists. I.v.
      administration of the selective tachykinin NK2 receptor antagonists, MEN 10,627
      (10-100 nmol/kg) and SR 48968 (100-300 nmol/kg) or of the selective NK1
      antagonist SR 140333 (100 nmol/kg), at doses which do not affect the duodenal
      contractions induced by acetylcholine (5.5 mumol/kg i.v.), produced a prompt and
      long lasting suppression of the atropine-resistant reflex duodenal contractions
      produced by balloon distension in urethane-anesthetized rats, whilst SR-48965
      (300 nmol/kg), the enantiomer of SR-48968 devoid, of NK2 receptor blocking
      activity, was without effect. I.v. administration of the selective NK1 receptor
      agonists [Sar9] substance P sulfone and septide or of the NK2 receptor selective
      agonist, [beta Ala8] neurokinin A(4-10) produced dose-dependent contractions of
      the duodenum. SR 140333 (100 nmol/kg i.v.) selectively antagonized the duodenal
      contractions produced by [Sar9] substance P sulfone and septide without affecting
      those produced by [beta Ala8] neurokinin A(4-10). On the other hand, MEN 10,627
      (30-100 nmol/kg i.v.) and SR 48968 (100-300 nmol/kg i.v.) but not SR 48965 (300
      nmol/kg i.v.) antagonized, at a comparable extent, duodenal contractions induced
      by both the selective NK2 and NK1 receptor agonists. We conclude that endogenous
      tachykinins are involved in mediating atropine-resistant reflex contractions
      evoked by distension of the rat duodenum in vivo: both NK1 and NK2 receptors are
      activated by endogenous ligands to produce NANC contractions of rat duodenum in
      vivo. However, the contractile response to i.v. administered NK1 receptor
      agonists, [Sar9] substance P sulfone and septide, may involve the release of
      mediators producing smooth muscle contraction via NK2 receptors.

PMID- 8878065
TI  - Effect of epinine on tension of human renal arteries.
AB  - BACKGROUND: The present study aimed to characterize the effects of epinine, the
      active metabolite of ibopamine on tension development in human renal arteries.
      METHODS AND RESULTS: Experiments were performed on isolated human renal arteries
      rings obtained during surgery due to kidney tumors (n = 12). Epinine
      concentration-dependently relaxed isolated precontracted (PGF2 alpha) human renal
      artery rings (P < 0.05) in the presence of phentolamine, as effectively (epinine 
      30 +/- 4 mN, dopamine -31 +/- 5 mN) and with the same potency as dopamine
      (epinine EC50 0.7 mumol/l (0.4-1.2 mumol/l), dopamine 0.5 mumol/l (0.2-1.7
      mumol/l). This effect was antagonized by the specific D1-receptor-antagonist SCH
      23390. Effective beta-adrenoceptor antagonistic concentrations of propranolol did
      not affect epinine-induced vasorelaxation. In the absence of alpha- and beta
      adrenoceptor-antagonists the potency of epinine to contract renal artery rings
      was significantly higher compared to dopamine indicating a higher affinity of
      epinine to alpha-adrenoceptors. CONCLUSION: The present study provides evidence
      for direct vasodilatory effects of epinine via activation of D1-receptors on
      human renal arteries.

PMID- 8878066
TI  - Participation of nitric oxide in the relaxation of the rat gastric corpus.
AB  - Nitric oxide is an important mediator of the relaxation in the rat gastric
      fundus. The present study investigates the role of NO in the rat gastric corpus
      in vitro, since the corpus differs from the fundus with regard to its
      physiological function and its spontaneous motor behaviour. In the presence of
      guanethidine electrically induced relaxations of circular, mucosa-free corpus
      strips precontracted with bethanechol were concentration-dependently reduced by
      the NO-synthase inhibitors L-NG-nitro-arginine (L-NNA) or L-NG-nitro-arginine
      methyl-ester (L-NAME). The D-enantiomers were markedly less active. The
      inhibitory effect of L-NAME could be prevented by L-arginine. L-NNA and L-NAME,
      however, did not influence spontaneous motility or the bethanechol-induced
      contraction. Vasoactive intestinal polypeptide or sodium nitroprusside also
      relaxed the muscle strips, but these relaxations were not affected by L-NAME.
      When the corpus strips were stimulated electrically from baseline, they reacted
      with a contraction followed by relaxation. L-NNA or L-NAME blocked the relaxatory
      and enhanced the contractile component. In strips that also reacted with a
      rebound contraction, it was blunted by L-NAME. These effects of the NO-synthase
      inhibitors were abolished in the presence of atropine. Apamin increased the
      electrically induced contraction of the muscle strips. Inhibition of the
      relaxation together with a further shift to contraction could only be seen when
      apamin was combined with L-NNA. The inhibitory action of apamin and apamin + L
      NNA was not influenced by atropine. The results demonstrate a role of NO in the
      relaxation of the circular muscle of the rat gastric corpus both at a
      postsynaptic site and via inhibition of acetylcholine release. The relaxation
      induced by vasoactive intestinal polypeptide does not involve NO.

PMID- 8878067
TI  - KATP channel openers reverse immune complex-induced airways hyperreactivity
      independently of smooth muscle relaxation.
AB  - Many openers of ATP-dependent potassium channels (KATP channel openers) cause
      bronchorelaxation, whereas only a few of them have been claimed to reverse
      airways hyperreactivity. We investigated whether the antihyperreactive effect is
      a general feature of KATP channel openers and whether this property is linked to
      their ability to relax airways smooth muscle. For this purpose, the potency of
      the four KATP channel openers, bimakalim, rilmakalim, levcromakalim and SDZ PCO
      400 ((-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-cyclopent -1 
      enyloxy)-2H-1-benzopyran-6-carbonitrile), to inhibit bombesin- or histamine
      induced bronchoconstriction and to reverse immune complex-induced airways
      hyperreactivity to histamine in guinea pigs, was compared to salbutamol,
      following intratracheal administration to minimize pharmacokinetic differences.
      Total lung resistance (RL) was determined in anaesthetized, ventilated guinea
      pigs. Bronchoconstriction, measured as increase in RL, was elicited in
      normoreactive animals by i.v. infusion of bombesin (100 ng/kg/min) or by i.v.
      injection of histamine (1.8-10 micrograms/kg). Airways hyper-reactivity was
      induced by acute i.v. administration of preformed immune complexes. I.v. bolus
      injections of histamine were used to define the sensitivity of the airways prior
      to and after the exposure to immune complex. Levcromakalim (ED50 = 150
      micrograms/kg), bimakalim (ED50 = 4 micrograms/kg), rilmakalim (ED50 = 40
      micrograms/kg) and SDZ PCO 400 (ED50 = 280 micrograms/kg) reverse bombesin
      induced bronchoconstriction with lower potency than salbutamol (ED50 = 1
      microgram/kg). The four KATP channel openers and salbutamol also reversed immune
      complex-induced airways hyperreactivity to histamine with ED50 values which were
      markedly lower than those for reversal of bombesin-induced bronchoconstriction;
      the rank order of potency was rilmakalim (ED50 = 0.2 microgram/kg) > bimakalim
      (ED50 = 0.5 microgram/kg) > SDZ PCO 400 (ED50 = 3.2 micrograms/kg) >
      levcromakalim (ED50 = 22 micrograms/kg). Salbutamol (ED50 = 0.008 microgram/kg)
      was the most potent compound in this test. Bimakalim, levcromakalim and SDZ PCO
      400 did not inhibit histamine-induced bronchoconstriction in normoreactive guinea
      pigs at doses which completely reversed immune complex-induced airways
      hyperreactivity to histamine. For rilmakalim and salbutamol, 60-130 times higher
      doses were needed for protection against histamine-induced bronchoconstriction in
      normoreactive guinea pigs than for reversal of airways hyperreactivity. There was
      a poor correlation between the ED50 values for inhibition of histamine- or
      bombesin-induced bronchoconstriction in normoreactive guinea pigs and the
      reversal of immune complex-induced airways hyperreactivity. It is thus concluded
      that the ability of KATP channel openers to reverse immune complex-induced
      airways hyperreactivity is independent of their ability to reverse or prevent
      bronchoconstriction and thus from their ability relax airway smooth muscle.

PMID- 8878068
TI  - Irreversible agonist and antagonist properties of isothiocyanatobenzyl
      imidazoline in albino rabbit iris muscles.
AB  - The alkylating agent isothiocyanatobenzyl imidazoline (IBI) was synthesized to
      investigate the unique receptor interacting properties of imidazolines. On the
      isolated rabbit iris sphincter, IBI produced concentration-dependent responses
      with an EC50 of 18 mumol/1, and at the highest concentration tested the maximum
      contraction of the tissue was 50% of the carbachol maximum. At equiactive
      concentrations with the similar washing procedure, the total duration of
      responses to IBI and carbachol was 24 and 3 min, respectively. After repeated
      washing, the sphineter relaxes to the control baseline of tone but, after
      reexposure to IBI for 6 h, failed to contract, indicating that desensitization or
      irreversible block has developed. Unlike with carbachol, the sphincter
      contraction to IBI was not affected by atropine 1 mumol/1, indomethacin 1
      mumol/1, verapamil 10 mumol/1, or nifedipine 10 mumol/1. At a higher
      concentration of nifedipine and papaverine 100 mumol/1, the response to IBI was
      blocked. Furthermore, the contractile response to IBI was abolished by Ca++
      removal from the medium. Under similar conditions, 26 +/- 8% of the maximum
      response to carbachol was preserved. Thus influx of extracellular as well as rise
      in intracellular Ca++ appears vital for the contractile response to IBI. IBI did
      not contract the iris dilator, but shifted the concentration-response curve to
      the alpha-adrenoceptor activator, phenylephrine, to the right with a reduction in
      the maximum response. The tissue failed to regain the sensitivity to
      phenylephrine after 6 h of repeated washing. Phentolamine and nifedipine provided
      a small but significant protection of the response to phenylephrine against the
      irreversible block by IBI. Based on chemical and pharmacological properties of
      IBI, it is concluded that the molecule acts in the rabbit as an irreversible
      agonist on unidentified receptors of the iris sphineter and an irreversible
      antagonist of multiple receptors on the iris dilator. These molecular properties
      of IBI are clearly different from that of the parent imidazoline molecule
      tolazoline.

PMID- 8878069
TI  - Superoxide anion release from neutrophils in growth hormone deficient adults
      before and after replacement therapy with recombinant human growth hormone.
AB  - The observations that growth hormone primes neutrophils and stimulates various
      activities of monocytes suggested that it plays a role in the regulation of
      leukocyte biology. The in vivo reduction of growth hormone levels may be
      responsible for to the functional impairment of leukocytes observed in growth
      hormone deficient children. Whether leukocyte function is impaired in growth
      hormone deficient adults is not known as yet. We therefore studied superoxide
      anion release from neutrophils and chemotaxis of monocytes in 15 patients with
      adult-onset growth hormone deficiency before and after a period of 6 months of
      replacement therapy with recombinant human growth hormone. Analyses were
      performed by comparing functions of the leukocytes from these patients with those
      from age and sex-matched healthy control subjects. Before growth hormone
      treatment, patients received appropriate replacement therapy with thyroid,
      adrenal and gonadal hormones. The dose of recombinant human growth hormone was
      0.25-0.5 U/kg/week (0.013-0.026 mg/kg/day) throughout the whole period of
      replacement therapy. In growth hormone deficient subjects, formylpeptide
      triggered release of superoxide anions from neutrophils was significantly
      suppressed by about 40% before treatment as compared to healthy control subjects.
      After 6 months of replacement therapy, neutrophil superoxide anion release was
      similar in patients and healthy individuals. Neither before nor after replacement
      therapy, however, was there a difference in monocyte migration between control
      and growth hormone deficient subjects. These data indicate that neutrophil
      function is somehow altered in growth hormone deficient patients, even when
      receiving appropriate therapy with thyroid, adrenal and gonadal hormones, but
      that neutrophil function can be restored to near normalcy by growth hormone
      replacement therapy. This would suggest that suppressed neutrophil respiratory
      burst is due to the deficiency in growth hormone.

PMID- 8878070
TI  - Obesity induced by unspecific early postnatal overfeeding in male and female
      rats: hypophagic effect of CCK-8S.
AB  - The response to cholecystokinin (CCK) as a satiety peptide in obesity or anorexia
      has been tested mainly in extreme models of food intake control. In the present
      study, the effect of CCK-8S on food intake was investigated in a nongenetic and
      less-stressful model of obesity due to unspecific early postnatal overfeeding in
      male and female rats. Reducing the normal litter size of ten to three newborn
      rats on day 3 of life led to an enhanced food intake resulting in an increased
      body weight until adulthood. Freely fed male and female, normal and obese rats
      were given 10 micrograms/kg CCK-8S i.p. on day 41 and 40 micrograms/kg CCK-8S on
      day 91 of life and food intake was measured for 24 h. Compared with treatment
      with saline (i.p.) 1 day before the test, the lower dose of 10 micrograms/kg CCK
      8S reduced food intake for 2 h in normal, but not in obese rats. Conversely, the
      higher dose of 40 micrograms/kg CCK-8S reduced food intake in both normal and
      obese rats for 2 h, but this effect was more evident in the obese rats. Moreover,
      the satiating effect of CCK-8S was more pronounced and longer lasting in male
      than in female rats. In summary, the data suggest that the response to CCK-8S
      differs in normal and obese rats and depends on sex.

PMID- 8878071
TI  - Experimental anxiety and antidepressant drugs: the effects of moclobemide, a
      selective reversible MAO-A inhibitor, fluoxetine and imipramine in mice.
AB  - Available evidence derived from behavioural and clinical studies indicates that
      antidepressant drugs may be effective as anxiolytic agents. In this connection,
      the present study was designed to assess the behavioural effects of three
      antidepressant drugs, i.e. imipramine (IMI), a non selective serotonin (5-HT) and
      noradrenaline re-uptake (NA) inhibitor, fluoxetine (FLU), a selective 5-HT re
      uptake inhibitor (SSRI) and moclobemide (MOC), a reversible inhibitor of type A
      monoamine-oxidase enzyme (RIMA) on anxiety, exploratory and locomotor activities
      in mice. The experiments used two animal models which attempt to separate these
      three factors: the "light-dark aversion" test and the "open-field" test. Naive
      female CD1 mice were administered intraperitoneally (i.p.) 30 min before testing
      with IMI (10, 20 and 40 mg/kg) or FLU (5, 10 and 20 mg/kg) or MOC (1, 5 and 10
      mg/kg) or vehicle. Results showed that IMI (10 and 20 mg/kg), FLU (10 and 20
      mg/kg) and MOC (1, 5 and 10 mg/kg) significantly reduced the aversive behavior of
      mice for the lit area in the light/dark aversion test, suggesting an anxiolytic
      like effect. In fact, vehicle controls preferred the dark box where they spent
      approximately 70% of their time, indicating that light serves as an anxiogenic
      stimulus. Importantly, the anxiolytic-like effects of these antidepressant drugs
      were not associated with any increase in locomotor activity. In summary, these
      data suggest that FLU and the new generation of RIMA, exemplified by MOC, in
      terms of probable efficacy and greater safety, are of interest as treatment for a
      broad spectrum of anxiety disorders.

PMID- 8878072
TI  - Further evidence for the subsensitivity of striatal AMPA receptors, induced by
      chronic haloperidol administration: an autoradiographic study.
AB  - The aim of the present study was to investigate the influence of chronic
      treatment with haloperidol on the striatal N-methyl-D-aspartate (NMDA), alpha
      amino-3-hydroxy-5-methyl-4-isoxasole-propionic acid (AMPA) and dopamine D2
      receptors using a quantitative autoradiography in rats. Haloperidol was given to
      animals in a dose of ca. 1 mg/kg/day in drinking water for 6 weeks or 3 months
      and was afterwards withdrawn for 5 days. Haloperidol increased by 20-50% the
      binding of [3H]spiperone in different regions of the caudate-putamen. Haloperidol
      decreased by ca. 30% the binding of [3H]AMPA in the ventrolateral region of
      intermediate part of the caudate-putamen, but did not influence the binding of
      [3H]MK-801. The present results suggest that, apart from supersensitivity to
      dopamine, chronic treatment with haloperidol also induces subsensitivity of
      striatal AMPA receptors.

PMID- 8878073
TI  - Analysis of the action of idazoxan calls into question the reliability of the rat
      isolated small mesenteric artery assay as a predictor for alpha 1-adrenoceptor
      mediated pressor activity.
AB  - We have studied the effects of idazoxan in rat aorta and small mesenteric artery.
      In the aorta, idazoxan behaved as a partial agonist (pKA = 6.30). Prazosin
      produced rightward shift (pA2 = 9.88) and steepening of the idazoxan curve. In
      contrast, idazoxan had no effect of basal tension in the mesenteric artery, but
      shifted the noradrenaline curve to the right in a parallel manner (pA2 = 6.12).
      The selective alpha 1-adrenoceptor agonist, indanidine, also behaved as a partial
      agonist in the aorta and produced no significant contractions of the small
      mesenteric artery. Since idazoxan and indanidine have been reported to raise
      blood pressure in the pithed rat via an action at vascular alpha 1-adrenoceptors,
      these results call into question the reliability of the small mesenteric artery
      assay as a predictor for alpha 1-adrenoceptor-mediated pressor activity in vivo.

PMID- 8878074
TI  - Presynaptic inhibitory serotonin autoreceptors in the human hippocampus.
AB  - Hippocampal slices were prepared from brain tissue of patients undergoing
      neurosurgery for epilepsy. The slices were incubated with 3H-serotonin (3H-5-HT)
      and then superfused with physiological salt solution containing 6-nitroquipazine.
      Tritium overflow was evoked either electrically (3 Hz) or by K+ 25 mM. The
      electrically evoked overflow of tritium was almost abolished by tetrodotoxin or
      by omission of Ca2+ ions. 5-HT 0.1 and 1 microM reduced the evoked overflow by 38
      and 55%, respectively. The effect of 5-HT 1 microM was abolished by the 5-HT1/2
      receptor antagonist methiothepin 1 microM, which, by itself, increased the evoked
      overflow by 59%. Tritium overflow evoked by high K+ in slices superfused with
      medium containing tetrodotoxin was reduced by 5-HT 1 microM by 49%. This effect
      was markedly attenuated by methiothepin 0.32 microM, which, by itself, tended to
      increase the evoked overflow. The results show that the serotoninergic neurones
      of the human hippocampus are endowed with presynaptic inhibitory autoreceptors.

PMID- 8878075
TI  - Pitfalls in multiple sclerosis epidemiology: the Israeli experience.

PMID- 8878076
TI  - Motor neuron disease in Hong Kong Chinese: epidemiology and clinical picture.
AB  - This study documents the clinical features, incidence and prevalence of motor
      neuron disease (MND) in Hong Kong Chinese. Patients with MND who were alive
      between 1989 and 1992 were recruited by retrieval of medical records from the
      four major hospitals in Hong Kong, and by referral of neurologists, neurosurgeons
      and medical consultants. Mortality statistics was provided by the Census and
      Statistics Department. A total of 84 cases were identified with a male
      preponderance of 1.98:1. The average annual period incidence was 0.31/100,000 and
      the point prevalence on December 31, 1992, was 0.95/100,000. The mean age at
      onset was 55.5 years (range 19-81) with a peak observed from 55 to 65 years. The
      clinical features are similar to other reported series of MND. The incidence and
      mortality of MND in Hong Kong are therefore lower than the worldwide figures of
      2.0/100,000 and 1.5/ 100,000, respectively.

PMID- 8878077
TI  - Standardization of the diagnosis of dementia in the Canadian Study of Health and
      Aging.
AB  - Standardization of diagnostic procedures for cognitive impairment in large
      epidemiologic surveys remains difficult. This paper reports results of diagnostic
      standardization in a subsample of 2,914 elderly (age 65 years+) Canadians from
      the Canadian Study of Health and Aging (CSHA; n = 10,263). The objectives were to
      measure the consistency of the CSHA diagnosis as a test of validity; to assess
      inter-rater reliability, and to assess the impact of neuropsychological data on
      the diagnosis of dementia. The CSHA clinical assessment included a nurse's
      examination, Modified Mini-Mental Status (3MS) exam and Cambridge Mental
      Disorders Examination, neuropsychological tests, medical history and examination,
      and laboratory investigations. A final diagnosis was reached in a consensus
      conference which incorporated preliminary diagnoses from both physicians and
      neuropsychologists. Computer algorithms, which were developed to check
      consistency between the clinical observations and the final diagnosis,
      demonstrated 98% concordance with DSM-III-R criteria for dementia and 92% with
      NINCDS-ADRADA (National Institute of Neurological and Communicative Disorders and
      Stroke and the Alzheimer's Disease and Related Disorders Association) criteria
      for probable Alzheimer's disease. Inter-rater agreement was high: kappa = 0.81
      for dementia/no dementia; kappa = 0.74 for normal/cognitive impairment, not
      dementia/ dementia. Comparisons of diagnoses between raters by clinical specialty
      revealed few systematic differences. The impact of neuropsychological input on
      the physician's diagnosis was most marked in the borderline cases between
      diagnostic categories.

PMID- 8878078
TI  - Effects of sequential neuropsychological testing of an elderly community-based
      sample.
AB  - The magnitude and importance of changes in scores of neuropsychological tests on
      retest in the elderly, especially over long time periods, is not well
      established. Three neuropsychological tests and one mental status test were
      initially administered to screen for potential dementia and were readministered
      to 380 of the surviving individuals 2.4 years later who either failed the
      screening examination or were an age matched control. Of the 380 women and men
      aged 65 and older, 56 were diagnosed as having Alzheimer disease (AD), 82 as at
      risk for developing AD, and 242 as having normal cognition. The present report
      focuses on changes in test scores between the two visits. In the normal and at
      risk groups, significant improvements were seen on retest of the Visual
      Reproduction Test (VRT), the Trails B test, and the Mini-Mental Status
      examination; verbal fluency decreased, and savings score of the VRT showed small
      variations. On most tests, scores of the AD group decreased. Practice effects,
      biases, and other variables may have played a role in the improvements seen in
      those labeled normal and at risk. If these results are confirmed, savings score
      of the VRT (which remained stable over time in normals and individuals at risk
      and decreased in patients with dementia) and verbal fluency (which decreased in
      all groups) may be better measures of true cognitive performance than the other
      tests that we evaluated.

PMID- 8878079
TI  - Effect of nitric oxide on propagated clusters of spontaneous motor waves in an ex
      vivo rabbit intestinal preparation.
AB  - The aim of this study was to determine whether nitric oxide can play a role in
      regulating the propagation of spontaneous motor activity in a rabbit intestinal
      preparation completely excluded from any central and vascular connection.
      Experiments were done on nine rabbits of either sex, weighing 2.5 +/- 0.5 kg
      (mean +/- SD). After one week of semiliquid diet the animals were sacrificed and
      a segment including the stomach, duodenum and part of the jejunum was removed and
      placed into a single chamber organ bath containing 1 L of oxygenated Krebs'
      solution. Four strain gauges connected to a Dynograph Recorder were sutured on
      the serosal surface 10 cm apart starting from the gastric antrum to the distal
      duodenum. Once the motor activity was stabilized, N-nitro-L-arginine methyl-ester
      (L-NAME) was added to the bath at increasing concentration from 10(-7) to 10(-4)
      M. Spontaneous motor activity was recorded, characterized by the cycling
      occurrence of bursts of waves, starting from the stomach and propagating to the
      descending duodenum. L-NAME at higher concentrations reduced the time interval
      between the bursts of waves with a concomitant increase in the propagation
      velocity of the motor activity. No change in the frequency of waves was detected.
      The effect of L-NAME was prevented by the administration of L-Arginine. This
      study suggests an important role for the nitric oxide pathway in the distal
      propagation of the spontaneous motor activity of the alimentary tract.

PMID- 8878080
TI  - High resolution electrical mapping in the gastrointestinal system: initial
      results.
AB  - High resolution electrical mapping in the gastrointestinal system entails
      recording from a large number of extracellular electrodes simultaneously. It
      allows the collection of signals from 240 individual sites which are then
      amplified, filtered, digitized, multiplexed and stored on tape. After recording,
      periods of interest can be analysed and the original sequence of activity
      reconstructed. This technology, originally developed to study normal rhythms and
      abnormal dysrhythmias in the heart, has been modified to allow recordings from
      the gastrointestinal tract. In this report, initial results are presented
      describing the origin and propagation of the slow wave in the isolated stomach
      and the isolated duodenum in the cat. These results show that in both organs it
      not uncommon to have more than one focus active during a single cycle. The
      conduction of slow waves from such a multiple pacemaker environment can become
      quite complex, and this may play a role in determining the contractile pattern in
      these organs.

PMID- 8878081
TI  - Volume shifts, unfolding and rolling of haustra in the isolated guinea pig
      caecum.
AB  - The large intestine extracts water from chyme and compacts chyme into faecal
      conglomerates; it is unclear what role the special pockets known as colonic
      haustra have in these events. Here we monitored the movements of haustra in
      isolated preparations of guinea pig caecum using videocamera and ultrasound and
      related them to contractions of muscle flaps and movements of glass beads in
      haustral pockets. We found that in partially filled caecal loops localized
      contractions of taeniae shift volume back and forth between adjacent haustra;
      volume unfolds haustral walls in a characteristic sweep with sequential
      intrahaustral folds popping out; cyclic contractions and relaxations of the fold
      then produce the caterpillar-like movement known as haustral rolling; ultrasound
      showed that haustral rolling made the haustral flow channel narrower and longer
      as haustral folds increase their height from 7.5 +/- 1.5 mm to 16 +/- 4 mm and
      their distance from 4.1 +/- 0.2 mm to 7.9 +/- 0.3 mm; luminal contents were
      alternatively shaken off the haustral wall, whirled around the lumen or left to
      settle. We also suspended the row of haustra between two taeniae inside a frame
      and attached flaps of taeniae and haustral folds to strain gauges to record their
      mechanical activity; both taeniae and haustral folds produced an undulating
      baseline tension; during rolling, folds produced phasic contractions at 17 +/- 2
      cycles min-1 which propagated distally across haustral septa; rolling constantly
      shuffled around glass beads placed inside the haustra. When we stimulated the
      intramural nerves to the caecum through bipolar electrodes, all contractile
      activity was temporarily inhibited and haustral septa flattened; a rebound
      contraction then propagated aborally from the caecal pole and swept the glass
      beads ahead of it. Thus, tonic contractions of taeniae shift caecal contents back
      and forth across haustral septa; expansion of haustra triggers haustral rolling
      which shuffles contents; both these movements produce local flow within and
      between haustra which might enhance the separation of solid and liquid colonic
      contents.

PMID- 8878082
TI  - Comparative evaluation of DQ-2511, a novel gastroprokinetic agent, with cisapride
      in ameliorative action on experimentally induced delayed gastric emptying.
AB  - We compared the main pharmacological effect of DQ-2511 (3-[[[2-(3,4
      dimethoxyphenyl)- ethyl]carbamoyl]methyl]amino-N-methylbenzamide), a novel
      gastroprokinetic agent, with that of cisapride. Single oral administration of DQ
      2511 (3-10 mg kg-1) caused similar significant improvements to delays in gastric
      emptying of semi-solid meals evoked by cholecystokinin-octapeptide (CCK8: 5
      micrograms kg-1, i.v.) in monkeys, to that with cisapride (3 mg kg-1). A 2-week
      oral treatment of unilaterally vagotomized rats with DQ-2511 (1-10 mg kg-1)
      lessened delays in gastric emptying, whereas cisapride (0.3-10 mg kg-1) had no
      effect under the same experimental protocols. In anesthetized rats, bolus
      intravenous injection of either compound (60 micrograms kg-1) enhanced gastric
      motility determined by means of strain gauge force transducers.
      Electrophysiological investigations revealed that bolus injection of DQ-2511 (6
      60 micrograms kg-1) depressed the afferent discharge rate of the ventral gastric
      branch of the vagus nerve, while cisapride showed no effect. These results
      suggest that the mechanism of ameliorative action of DQ-2511 on delayed gastric
      emptying may differ from that of cisapride.

PMID- 8878083
TI  - Effect of glucose and lipids on intestinal absorption of sorbitol: role of
      gastric emptying.
AB  - The aim of our study was to test the hypothesis that the better absorption of
      sorbitol when ingested with glucose could be related to a delayed gastric
      emptying. We tested the effect of the ingestion of glucose and lipids on the
      gastric emptying and intestinal absorption of sorbitol in six healthy volunteers,
      using gastric scintigraphy and hydrogen breath test. After an overnight fast,
      subjects ingested in random order, on 48-h test periods separated by at least one
      week, the following solutions: (a) 20 g sorbitol alone; (b) 20 g sorbitol and 20
      g glucose; (c) 20 g sorbitol and 9 g lipids. Isotopic acquisitions were taken for
      3 h following the ingestion of sorbitol labelled with 111Indium. Hydrogen
      concentration was measured in end-expiratory samples during 5 h, and the areas
      under the breath hydrogen curve, reflecting the amounts of sorbitol unabsorbed in
      the small bowel, were compared between periods. Mean area under the curve was 397
      +/- 159 when sorbitol was ingested alone, and this was significantly lower when
      ingested with glucose or lipids (313 +/- 181 and 337 +/- 135, respectively; P <
      0.05). The three curves of sorbitol gastric emptying differed significantly from
      each other, the gastric emptying being the slowest for sorbitol plus lipids, and
      the fastest for sorbitol taken alone. We found a positive correlation between the
      half-emptying time and the hydrogen areas under the curve (r = 0.46, P = 0.05).
      In conclusion, our study demonstrates that adding glucose or lipids to a solution
      of sorbitol slows the gastric emptying of sorbitol, resulting in a better
      intestinal absorption of sorbitol.

PMID- 8878084
TI  - Intraluminal micromanometry: an evaluation of the dynamic performance of micro
      extrusions and sleeve sensors.
AB  - Conventional manometric techniques are unsuitable for studies in premature
      infants and small laboratory animals. We have therefore developed silicone rubber
      5-lumen and 10-lumen micromanometric extrusions with an o.d. 2.0 mm and lumina of
      0.35 mm i.d. This study evaluates the suitability of microextrusions for
      intraluminal perfusion manometry. Pressure offset, post-occlusion pressure rise
      rate and sphincter model studies were used to assess the manometric performance
      of the extrusions and a miniature sleeve sensor (25 mm long) at infusion rates of
      0.01-0.1 mL min-1. Micro-extrusions (5-lumen/10-lumen, respectively) had offsets
      (per 100 cm of length) of 3.8/5.0 mmHg at 0.01 mL min-1 and 25.6/26.2 mmHg at 0.1
      mL min-1 and rise rates (in 160 cm lengths) of 64/43 mmHg sec-1 at 0.01 mL min-1
      and 330/224 mmHg sec-1 at 0.1 mL min-1. Infusion rates 0.025 mL min-1 produced
      rise rates 100 mmHg sec-1. The miniature sleeve sensor had minimal resistance to
      perfusion, rise rates of 3 mmHg sec-1 at 0.01 mL min-1 and 23 mmHg sec-1 at 0.1
      mL min-1 and recorded pressure as accurately as a side hole. We conclude that the
      performance of micromanometric extrusions and sleeves is sufficient for
      intraluminal perfusion manometry.

PMID- 8878085
TI  - Difficulty in estimating localized bowel contraction by colonic manometry: a
      simultaneous recording of intraluminal pressure and luminal calibre.
AB  - To examine whether or not intraluminal pressure changes at a site in the human
      colon reflect with fidelity the local bowel wall contractions or relaxation,
      endoscopic recording of the changes in colonic calibre as a parameter of the
      motor events with simultaneous manometry was performed at a fixed site in a
      prepared sigmoid colon during the interdigestive state. In four of the 12
      subjects, a total of 20 phasic pressure waves with an amplitude of 13-22 mmHg and
      a duration of 13-18 sec were obtained in a 20 min recording session. Eighteen of
      the 20 phasic pressure waves (90%) were associated not with a decrease
      (contraction) but with an increase in the calibre (relaxation). The pressure
      change began 0.2-8.4 sec (mean: 4.5 sec) behind and ended-1.8 to 8 sec (mean: 3.5
      sec) ahead of the calibre change. In the other eight subjects, no phasic pressure
      change was recorded in the presence of an overt calibre change. We conclude that
      manometric phasic pressure change recorded at a site in the empty human colon is
      not necessarily correlated with the localized contractile activity. Extrapolation
      of pressure profiles in the colon to motor events at the manometric site should
      be cautious.

PMID- 8878086
TI  - The dorsal vagal complex of the ferret: anatomical and immunohistochemical
      studies.
AB  - To further the understanding of gastrointestinal function in this species, and in
      particular to advance our own work concerning central emetic pathways, the
      cytoarchitecture and the distribution of eight neurochemicals were studied in the
      ferret dorsal vagal complex (DVC; area postrema, nucleus of the solitary tract
      [nTS] and dorsal motor nucleus of the vagus). The cytoarchitectural features of
      this region in the ferret were similar to those seen in other species; however,
      the ferret possesses a particularly large and distinct subnucleus gelatinosus of
      the nTS. Dense calcitonin gene-related peptide-immunoreactivity was found in the
      gelatinous, interstitial and commissural subnuclei of the nTS, with lesser
      amounts in other regions of the DVC. Enkephalin-immunoreactivity of varying
      densities was found throughout the DVC. Moderate to dense galanin
      immunoreactivity was observed throughout the DVC, with the exception of the
      subnucleus gelatinosus of the nTS, from which it was virtually absent. Dense
      neuropeptide Y-immunoreactivity was observed in the subnucleus gelatinosus and
      interstitial subnucleus, with moderate staining in other regions of the DVC.
      Neurotensin immunoreactivity was very sparse or absent. Immunoreactivity for
      serotonin was sparsely distributed throughout the DVC. Moderate somatostatin
      immunoreactivity was observed over a large portion of the DVC, but was virtually
      absent from the gelatinosus and interstitial subnuclei. Substance P
      immunoreactivity was observed throughout the DVC and was particularly dense in
      the dorsal/dorsolateral subnucleus and the dorsal aspects of the medial and
      commissural subnuclei. In terms of its cytoarchitecture the DVC of the ferret is
      more similar to the cat than the rat, especially with regard to the area postrema
      and the subnucleus gelatinosus of the nTS. The distribution of neuroactive
      substances was largely similar to other species; however, differences were
      present particularly in patterns of immunoreactivity for enkephalin, serotonin,
      neuropeptide Y and somatostatin.

PMID- 8878087
TI  - D3 receptor expression within the basal ganglia is not affected by Parkinson's
      disease.
AB  - Quantitative receptor autoradiography and in situ hybridization were used to
      investigate the expression of dopamine D3 receptors in sections of human brain
      containing limbic (nucleus accumbens) and striatal (caudate nucleus, putamen)
      regions. High levels of dopamine D3 receptor mRNA and specific [3H](+/-)7-hydroxy
      N,N-di-N-propyl-2-aminotetralin ([3H]7-OH-DPAT) binding sites were detected in
      the nucleus accumbens with lower levels in the caudate nucleus and putamen. No
      difference in D3 receptor expression was observed between normal and parkinsonian
      brain. These results indicate that D3 receptor expression is not altered in
      Parkinson's disease. In addition, they suggest that dopamine release in striatal
      and limbic areas is not necessary for maintenance of D3 receptor expression.

PMID- 8878088
TI  - Calcium-dependent potentiation of M-current in bullfrog sympathetic neurons.
AB  - Whole-cell voltage-clamp recordings were made from cultured bullfrog sympathetic
      neurons to measure the steady-state activation curve of M-type potassium current.
      When measured with a calcium-deficient (10 nM) pipette solution M-conductance was
      4.8 nS at -35 mV having the 50%-activation voltage at-20 mV. Respective values
      were 17.2 nS at -35 mV with the 50%-activation voltage at -42 mV when measured
      with a calcium-rich (1 microM) solution, indicating the hyperpolarizing
      displacement of the activation curve with high internal calcium. It is suggested
      that intracellular calcium ions can modulate kinetics of M-current which thereby
      regulate the number of M-channels being open at given membrane potentials.

PMID- 8878089
TI  - Sympathectomy induces c-Jun in adult trigeminal neurons: an immunohistochemical
      and tract-tracing study.
AB  - The induction of the immediate early gene product c-Jun was investigated in
      trigeminal ganglia following surgical removal of the superior cervical ganglion
      (SCG). A 5-fold increase in c-Jun-immunoreactive neurons was detected by 48 h
      post-surgery in ipsilateral trigeminal ganglia of sympathectomized rats. This
      increase persisted for 6 days. When examined 4 months after sympathectomy, c-Jun
      expression had returned to basal levels. The possibility that trigeminal neurons
      project to the SCG, and therefore induce c-Jun by being axotomized by
      sympathectomy, was also examined using retrograde fluorescent tracing. A very
      limited number of trigeminal neurons were retrogradely labeled from the SCG.
      These data indicate that c-Jun induction occurs in sensory neurons following
      perturbations to sympathetic ganglia, and that trigeminal neurons may project to
      the SCG, but that c-Jun induction cannot be ascribed to axotomy following
      surgical sympathectomy. Thus, these findings support anatomical and functional
      interconnections between the sensory and autonomic nervous systems. The
      relationship of c-Jun induction with plasticity phenomena is discussed.

PMID- 8878090
TI  - Blockade of isoproterenol-induced synaptic potentiation by tetra-9-aminoacridine
      in the rat amygdala.
AB  - The effects of tetrahydro-9-aminoacridine (THA) on beta-adrenoceptor activation
      induced synaptic potentiation were studied in brain slices of the rat amygdala
      using intracellular recording techniques. To exclude the involvement of N-methyl
      D-aspartate (NMDA) receptors, all the experiments were performed in the presence
      of NMDA receptor antagonist, D-APV (50 microM). Bath application of isoproterenol
      (Iso; 15 microM) results in a long-lasting enhancement of the amplitude of
      excitatory postsynaptic potentials (EPSPs) to 200 +/- 6% of baseline. Forskolin,
      which directly activates adenyl cyclase, produces a similar effect suggesting
      that Iso may act through a cyclic AMP-dependent mechanism. Pretreatment of the
      slices with THA (300 microM) completely abolishes the Iso- and forskolin-induced
      synaptic potentiation. We hypothesize that the locus of THA/beta-adrenoceptor
      interaction is presynaptic; the underlying mechanism is likely due to THA's
      depression of transmitter release via a presynaptic blockade of voltage-dependent
      Ca2+ channels.

PMID- 8878092
TI  - Cellular response in the cerebellum after midline traumatic brain injury in the
      rat.
AB  - We evaluated the response of microglia and Purkinje cells in the cerebellum at 1,
      2, 3, 7 and 10 days after a midline fluid percussion brain injury. There was
      marked activation of microglia and a significant loss of Purkinje cells in the
      vermis by 7 days postinjury. These findings emphasize the vulnerability of the
      cerebellum to midline traumatic brain injury.

PMID- 8878091
TI  - Effects of peripheral nerve ligation on expression of mu-opioid receptor in
      sensory ganglion neurons: an immunohistochemical study in dorsal root and nodose
      ganglion neurons of the rat.
AB  - The present study was attempted to examine if mu-opioid receptor (MOR) might be
      transported by axonal flow peripherally through peripheral axons of somatic
      sensory ganglion neurons. After unilateral ligation of the sciatic nerve or the
      vagus nerve distal to the dorsal root ganglion (DRG) or nodose ganglion (NG), MOR
      like immunoreactivity (MOR-LI) of neuronal cell bodies in the DRG of the fourth
      and fifth lumbar nerves, NG, ambiguus nucleus (Amb) and dorsal motor nucleus of
      the vagus nerve (DMV) on the side of the ligation was apparently reduced within 1
      week after the nerve ligation. However, within 24 h after the nerve ligation, a
      transient enhancement of MOR-LI was observed in cell bodies of DRG neurons,
      sciatic nerve stump proximal to the ligature, and cell bodies of NG neurons on
      the side of the ligation; such a transient enhancement of MOR-LI was not detected
      in the Amb and DMV. The results suggest that MOR undergoes centrifugal axonal
      flow in peripheral axons of somatic and visceral sensory ganglion neurons, and
      that MOR synthesis in sensory ganglion neurons is vulnerable to damage of the
      peripheral axons.

PMID- 8878093
TI  - Differential isoform-specific regulation of calcium-independent protein kinase C
      in rat cerebral cortex.
AB  - Regulation of the Ca(2+)-independent protein kinase C (PKC) activity and isoforms
      by phorbol esters was investigated in rat cerebral cortex. Loss of soluble PKC
      eta immunoreactivity from the soluble fraction was dramatic with only a small
      increase in the membrane fraction. The kinetics of PKC epsilon and -delta
      translocation were slower than that for PKC eta, while phorbol esters had no
      effect on PKC zeta translocation. Despite the translocation of PKC delta, 
      epsilon and -eta from the soluble to the membrane fraction, both fractions showed
      a loss of PKC activity. These data indicate that the rates of translocation,
      inactivation and/or downregulation appear to be different not only among these
      Ca(2+)-independent isozymes, but also from that reported for the Ca(2+)-dependent
      PKCs. In addition, these results emphasize the importance of measuring both
      Ca(2+)-independent PKC activity and immunoreactivity in evaluating activation of
      these isoforms.

PMID- 8878094
TI  - CGP 35348 and CGP 55845A block the baclofen-induced depression of dorsal root
      evoked potentials in lumbar motoneurons of the neonatal rat.
AB  - In vitro brainstem-spinal cord preparations isolated from neonatal (0-5 days old)
      rats were used to investigate the GABAB receptor-mediated modulation of the
      dorsal root evoked potentials in lumbar motoneurons recorded intracellularly. The
      GABAB receptor agonist, baclofen, at low concentrations (1-10 microM), caused a
      reduction of the amplitude of the monosynaptic excitatory postsynaptic potential
      (EPSP), in a concentration-dependent manner. The depression of EPSPs was likely
      exerted at a presynaptic level since it occurred without any significant change
      of the passive membrane properties of the motoneurons. The two GABAB receptor
      antagonists, CGP 35348 and CGP 55845A blocked the effects of baclofen. These two
      compounds may be useful tools to study the evolution of GABAB receptor-mediated
      presynaptic inhibition during ontogenesis.

PMID- 8878095
TI  - Antidepressant-like effects of p-synephrine in mouse models of immobility tests.
AB  - We studied the effects of p-synephrine on the immobility behaviors and on the
      spontaneous motor activity in mice. p-Synephrine at oral doses from 1 to 10 mg/kg
      significantly decreased the duration of immobility in the tail suspension test
      and the forced swimming test in mice. At 30 mg/kg, the duration of immobility was
      returned to control values in both tests. Subcutaneous administration of prazosin
      hydrochloride (62.5 micrograms/kg), an alpha 1 adrenoceptor antagonist, blocked
      the p-synephrine (3 mg/kg)-induced decrease in immobility in the tail suspension
      test. p-Synephrine did not change the spontaneous motor activity at oral doses
      from 0.3 to 10 mg/kg. These results suggest that p-synephrine elicits an
      antidepressant-like activity in mouse models of immobility tests, through the
      stimulation of alpha 1 adrenoceptors.

PMID- 8878096
TI  - A quantitative approach to identify and isolate pure populations of fluorescently
      labeled adult retinal ganglion cells using a pressure-driven microaspiration
      technique.
AB  - We developed a technique to obtain pure subsets of neuronal populations for
      specific analysis at the molecular level. The fact that most areas of the brain
      consist of mixed types of neuronal and non-neuronal cells was circumvented by
      retrograde labeling of retinal ganglion cells (RGCs) either from the superior
      colliculus (SC) or the optic nerve (ON) using fluorescent dyes (4Di-10ASP or
      Rhodamine). Subsequent enzymatic dissociation of the retina with papain allowed
      to identify and collect pure populations of RGC by using the pressure-driven
      microaspiration technique. Enzymatic treatment and additional mechanical
      dissociation destroy most of the vulnerable ganglion cells leaving between 1.8%
      and 6% of the labeled cells intact. This low outcome was consistent among the
      techniques used to apply the dye and the two different dyes used in the study.
      However, the total numbers of cells obtained from each retina were sufficient to
      collect about 200 cells within 1 day and process these cells for molecular
      biology. As an example of further processing of collected cells, the expression
      of beta-actin gene was analyzed.

PMID- 8878097
TI  - Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar
      neuronal cells induced by hydroxyl radicals.
AB  - The ability of oxidative stress to induce apoptosis, and the effect of Ginkgo
      biloba extract (EGb761) on this induction were studied in primary cultured rat
      cerebellar neuronal cells. Cells were exposed to hydroxyl radicals by treating
      them with 20-50 microM hydrogen peroxide (H2O2) and 100 microM ferrous sulfate.
      Hydroxyl radical treatment fragmented the DNA in a manner typical of apoptosis
      cells, producing a ladder pattern of 200 base pair increments on 1% agarose gel
      electrophoresis. Pretreatment of cells with 100 micrograms/ml EGb reduced
      hydroxyl radical induced cells apoptosis (determined by flow cytometry) and DNA
      fragmentation. The results indicate that hydroxyl radicals induce apoptosis in
      rat cerebellar neuronal cells and this induction can be prevented by EGb.

PMID- 8878098
TI  - Locomotion coincides with c-Fos expression in related areas of inferior olive and
      cerebellar nuclei in the rat.
AB  - Rats that had been walking on a rotating drum for a period of 75 min,
      demonstrated expression of the immediate early gene c-Fos in specific areas of
      the inferior olive and cerebellar nuclei. Non-walking control rats did not show
      consistent Fos-like immunoreactive labelling in these nuclei. Fos-like
      immunoreactive olivary neurons were consistently found in the caudolateral parts
      of the dorsal accessory olive and in its dorsal fold, and within specific areas
      of the medial accessory and principal olives. In the cerebellar nuclei,
      immunoreactive cells were found in the medial part of the anterior interposed
      nucleus, in the interstitial cell groups, and within specific parts of the
      medial, posterior interposed, and lateral nuclei. The lateral vestibular nucleus
      as well as the ventral part of the magnocellular red nucleus also displayed
      positive neurons. Most of these positive areas are known (1) to be related to the
      spinal cord and (2) to be anatomically linked. These results are in line with a
      presumptive role of the olivo-cerebellar system in ongoing movement control.

PMID- 8878099
TI  - Hypnotic and hypothermic effects of melatonin on daytime sleep in humans: lack of
      antagonism by flumazenil.
AB  - In this double-blind, placebo-controlled study we investigated whether 10 mg
      flumazenil, a pure benzodiazepine antagonist, can block the hypnotic and
      hypothermic effects of 3 mg melatonin. The design comprised four 7-h (1200-1900
      h) testing periods, preceded by a 'no-treatment' adaptation period of the "7/13'
      sleep-wake paradigm. Six young healthy adult males were paid to participate.
      During each experimental period, tablets were administered at 1145 h (flumazenil
      or placebo) and at 1200 h (melatonin or placebo) in a randomized, double-blind,
      partially repeated Latin square design. Polysomnographic recordings and core body
      temperature recordings revealed that melatonin, either in combination with
      placebo or with flumazenil, significantly increased the amounts of sleep, and
      decreased core body temperature in comparison with placebo alone or the
      combination of flumazenil plus placebo. These results do not support the
      hypothesis that melatonin exerts its hypothermic and hypnotic effects via the
      central benzodiazepine receptors.

PMID- 8878100
TI  - Voltage dependency of light-evoked on-off transient amacrine cell responses in
      carp retina.
AB  - The voltage dependency of the ON and the OFF components of transient amacrine
      cell responses was studied using two-electrode voltage-clamp and current-clamp
      techniques in the isolated retina of the carp. The two independent approaches
      gave similar data. When cells were voltage clamped near their resting potentials,
      both response components were associated with transient inward currents.
      Hyperpolarization increased response size (current or voltage) whilst
      depolarization decreased it. Response reversal, or a tendency for it, occurred at
      membrane potentials significantly more positive than the resting level with some
      quantitative variability. These data support the view that the ON-OFF
      depolarizations represent basically excitatory postsynaptic potentials and that
      the transience of the responses cannot mainly be due to any voltage-dependent
      conductance.

PMID- 8878101
TI  - Functional antagonism of mu-, delta- and kappa-opioid antinociception by orphanin
      FQ.
AB  - Orphanin FQ (OFQ) is the recently isolated endogenous ligand for the orphan
      opioid-like receptor, LC132. Initial reports suggested that OFQ increased pain
      sensitivity when injected intracerebroventricularly (i.c.v.) in mice. However, we
      have recently demonstrated that OFQ is instead an anti-opioid peptide that
      reverses morphine- and opioid-mediated stress-induced antinociception. Morphine
      binds to multiple opioid receptor types (mu, delta, and kappa). The present study
      was designed to examine specific interactions of OFQ with antinociception
      mediated by each receptor type. To this end, mice were administered i.c.v.
      cocktails containing either vehicle or OFQ (10 nmol) and a mu-specific ([D-Ala2,
      N-Me-Phe4-Gly-ol]enkephalin; DAMGO; 0-0.1 nmol), delta-specific ([D-Pen2, D
      Pen5]enkephalin; DPDPE; 0-50 nmol), or kappa-specific (U-50,488H; 0-1000 nmol)
      agonist. As we have shown previously, OFQ alone had no effect on nociceptive
      sensitivity. OFQ was, however, able to completely block supraspinal
      antinociception produced by all three receptor type-selective agonists. We
      conclude, therefore, that OFQ functionally antagonizes mu (and (opioid receptors,
      and may play a general role in opioid modulation.

PMID- 8878102
TI  - Signal-regulated proteins and fibroblast growth factor receptors: comparative
      immunolocalization in rat retina.
AB  - We compared the immunolocalization of fibroblast growth factor (FGF)-R1 and FGF
      R2 with that of several intracellular signalling proteins in rat neural retina.
      Only the serine/threonine extracellular signal-related kinases (ERK) and
      lipocortin/annexin 6, a major calcium-binding protein, appeared to be co
      localized with FGF-R1 and FGF-R2 in all subfields of the neural retina. In
      particular, ERK appeared to be present in perikarya of ganglion cells and
      synaptic layers as did these receptors. Possible implications of these results
      with regard to neuroprotective role of FGF are discussed.

PMID- 8878103
TI  - Bromocriptine prevents spinal motor neuron death following sciatic nerve
      transection in neonatal rats.
AB  - Bromocriptine, a potent dopamine D2 receptor agonist, appears to have
      neuroprotective actions. In order to investigate the effect of bromocriptine on
      axotomy-induced cell death, we have examined the survival of spinal motor neurons
      after sciatic nerve transection in the neonatal rats. Newborn rats were
      anesthetized with hypothermia. Sciatic nerve was transected near the obturator
      tendon in the left thigh. Animals were then treated daily with bromocriptine for
      14 days with intraperitoneal injections. Control animals received PBS in the same
      fashion. After the treatment, the number of spinal motor neurons in the L4-6 was
      counted. There is approximately a 50% loss of spinal motor neurons in the PBS
      treated group. By contrast, bromocriptine prevents spinal motor neuron death
      after axotomy. The motor neuron diameter on the lesioned side is significantly
      larger in the bromocriptine-treated group. These results are consistent with the
      possible role of bromocriptine as a survival factor for developing spinal motor
      neurons.

PMID- 8878104
TI  - Functional properties of postganglionic sympathetic neurones supplying the
      submandibular gland in the anaesthetized rat.
AB  - Sympathetic neurones supplying the submandibular salivary gland innervate blood
      vessels, secretory and myoepithelial cells. Here we examined whether these
      functionally different sympathetic neurones show distinct reflex response
      patterns. In anaesthetized rats, single unit activity was recorded from
      postganglionic axons projecting to the gland. Neurones were tested for their
      responses to stimulation of baroreceptors, cutaneous nociceptors and cold
      receptors and to gustatory stimuli applied to the tongue. Respiratory modulation
      was also analysed. Only a few postganglionic neurones identified electrically (5
      10%) were spontaneously active. They were excited by noxious and cold stimuli,
      inhibited by baroreceptor stimulation and exhibited respiratory modulation. None
      of the units responded to gustatory stimuli. Thus, in anaesthetized rats
      spontaneously active sympathetic neurones supplying the submandibular gland
      behave like vasoconstrictor neurones. Sympathetic neurones with other functions
      are probably silent.

PMID- 8878105
TI  - Representation of reaching and grasping in the monkey postcentral gyrus.
AB  - In area 2 and further caudal part of the alert monkey's postcentral gyrus, we
      found neurons which were activated preferentially or only by monkey's self
      initiated hand actions to reach or grasp objects. Among them we studied those
      neurons which were selective to either (1) projecting the arm and stretching
      digits toward an object (reaching); (2) grasping with the first and the second
      digit (radial grasp, precision grip); (3) grasping with the ulnar digits and
      palmar skin (ulnar grasp, whole hand grip); or (4) scratching or touching an
      object with distal digit pads and nails. Neurons of the radial grasp type were
      found in the lateral part of the digit region while all other types of neurons
      were found in the medial part. Each of hand action neurons was found in a cluster
      of neurons which had common receptive fields corresponding to effective sites for
      the particular type of grasping.

PMID- 8878106
TI  - ONO-1603, a potential antidementia drug, shows neuroprotective effects and
      increases m3-muscarinic receptor mRNA levels in differentiating rat cerebellar
      granule neurons.
AB  - We have reported that the antidementia drug tetrahydroaminoacridine (THA; 30
      microM) is neuroprotective and neurotrophic and selectively increases m3
      muscarinic acetylcholine receptor (mAChR) mRNA levels in differentiating
      cerebellar granule cells. Here, we examined whether novel prolyl endopeptidase
      inhibitor ONO-1603, a potential antidementia drug, induces similar effects in
      these cerebellar neurons. Supplement of ONO-1603 (0.03 microM) to cultures grown
      in 15 mM KCl-containing media was found to markedly promote neuronal survival and
      neurite outgrowth and enhance [3H]N-methylscopolamine binding to mAChRs.
      Moreover, ONO-1603 increased the level of m3-mAChR mRNA and stimulated mAChR
      mediated phosphoinositide turnover. The common actions of ONO-1603 and THA
      suggest that these properties could be related to their putative antidementia
      activities and that this model system may be used to screen for drugs effective
      in the treatment for Alzheimer's disease.

PMID- 8878107
TI  - Effects of central alpha-adrenergic agonists on hormone-induced 3% NaCl and water
      intake.
AB  - Male rats received intracerebroventricular (ICV) renin (600 ng) or daily
      subcutaneous injections of deoxycorticosterone (5 mg) to induce 3% NaCl and water
      intake. Noradrenaline (NOR; 40-160 nmol) and clonidine (CLO; 5-20 nmol) injected
      ICV induced 70 to 100% inhibition of the intakes. Phenylephrine (PHE; 40-160
      nmol) injected ICV induced 60 to 95% inhibition of the intakes. NOR and PHE
      induced a stronger inhibition on the 3% NaCl intake induced by renin than on the
      intake induced by deoxycorticosterone (DOC), and CLO did the opposite. CLO was
      always more effective than PHE to induce inhibition of the intakes. The results
      suggest that NOR inhibits hormone (angiotensin II, aldosterone)-induced NaCl
      intake by acting mainly on alpha 2-adrenergic receptors.

PMID- 8878108
TI  - Hypoxanthine-guanine phosphoribosyltransferase (HPRT) expression in the central
      nervous system of HPRT-deficient mice following adenoviral-mediated gene
      transfer.
AB  - In this study we show that recombinant adenovirus can augment hypoxanthine
      guanine phosphoribosyltransferase (HPRT) levels in the central nervous system
      (CNS) of HPRT-deficient mice. Recombinant adenovirus containing the cDNA for rat
      HPRT (rHPRT) expressed from the Rous sarcoma virus LTR (RSV LTR) was constructed
      (AdRSVrHPRT). AdRSVrHPRT was injected into the right caudate nucleus of 7-week
      old HPRT-deficient mice. Brains were analyzed for gene transfer, transgene
      expression and function by DNA PCR, in situ RNA hybridization, and enzyme
      bioactivity. The results show that rHPRT cDNA delivered by an adenoviral vector
      can augment HPRT levels in brain tissue and documents the utility of gene
      transfer to restore HPRT activity in an HPRT-deficient CNS.

PMID- 8878109
TI  - Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients
      with apolipoprotein E allele epsilon 4 during 14 months follow-up.
AB  - The concentration of tau protein is elevated in the cerebrospinal fluid (CSF) in
      Alzheimer's disease (AD), suggesting that CSF tau may be a useful biochemical
      diagnostic marker for this disorder. We investigated CSF tau concentrations on
      two occasions in AD (n = 18), mild cognitive impairment (MCI, n = 9) and other
      dementing disease (OD, n = 9) by ELISA (Innotest hTau Antigen, Innogenetics,
      Belgium). Tau levels were statistically significant higher in the AD group than
      in MCI and OD groups on both occasions. Twelve of the AD patients showed
      increasing values of tau at follow-up and six demonstrated diminished values. All
      AD patients with increasing tau were carriers of one or two epsilon 4 alleles of
      the apolipoprotein E (APOE, gene. Of those AD cases with decreasing tau levels
      only three individuals had the epsilon 4 allele, a difference that was
      statistically significant (P < 0.05). These findings suggest that there may be
      apolipoprotein E (apoE) isoform-specific differences of tau regulation in AD.

PMID- 8878110
TI  - Chloroquine specifically impairs Merkel cell mechanoreceptor function in isolated
      rat sinus hairs.
AB  - The function of Merkel cells in mechanotransduction has remained controversial
      Single unit recordings were made from Merkel cell receptors (sinus hair type I,
      St I) and another slowly adapting mechanoreceptor (sinus hair type II, St II) in
      isolated rat sinus hairs by applying controlled mechanical displacements to the
      hair shaft. Chloroquine (50-300 microM) caused a concentration dependent
      inhibition of Merkel cell receptor responses to mechanical stimulation. In
      contrast, both stimulated and spontaneous spike activity of St II receptors was
      increased by the same concentrations of chloroquine. Ultrastructural examination
      of chloroquine treated sinus hairs revealed swollen Merkel cells with multiple
      vacuoles and randomly distributed granules while other neural and surrounding
      structures showed no striking morphological changes. These results suggest that
      the Merkel cell plays a mechanotransducer role in Merkel cell receptors.

PMID- 8878111
TI  - Expression of alpha subunit genes of nicotinic acetylcholine receptors in human
      lymphocytes.
AB  - Using immunohistochemistry and in situ hybridisation, we have studied whether
      alpha-subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in
      human lymphocytes. Cells were isolated by differential low speed gradient
      centrifugation from heparinised venous blood of 10 healthy volunteers. Receptor
      sites were visualised using the monoclonal antibody WF6 which specifically
      recognises alpha-isoforms from several species including man. For visualisation
      of transcripts, digoxigenin-labelled cRNA probes for alpha 4- and alpha 3
      subunits were used. Immunostaining revealed specific binding of WF6 to isolated
      human lymphoid cells. The antibody was bound to most cells and concentrated
      preferentially in the perinuclear/surface region. The immunoreactivity resembled
      that observed after application of an antibody recognising CD4 surface proteins
      which was conducted for comparison. In situ-hybridisation revealed that the alpha
      4-subunit genes of nAChRs was expressed in lymphocytes of all probands. The alpha
      3-subunit was found, with lower intensity than alpha 4-transcripts, in eight of
      the 10 individuals. Control incubations with corresponding sense cRNAs were
      negative. It is concluded that human lymphocytes are able to express alpha
      subunit genes of nAChRs.

PMID- 8878112
TI  - NMDA-antagonists reverse increased hypoxic tolerance by preceding chemical
      hypoxia.
AB  - Glutamate antagonists mitigate hypoxic damage upon acute inhibition of energy
      metabolism. The goal of this study was to investigate their effect on increased
      hypoxic tolerance induced by preceding chemical inhibition of energy metabolism.
      While recovery of population spike amplitude (psap) is 30% of onset in slices
      prepared from control animals (15 min hypoxia, 45 min recovery), recovery exceeds
      90% in slices prepared from animals that underwent mild chemical hypoxia in vivo
      by treatment with 20 mg/kg 3-nitropropionic acid 1 h prior to slice preparation
      (p-slices). In p-slices perfused for 5 min with D(-)-2-amino-5-phosphonopentanoic
      acid (APV) (100 microM) 45 min prior to hypoxia, recovery declines to 42 +/- 13%
      (mean +/- SEM). In contrast, posthypoxic recovery after similar perfusion with 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM) is 72 +/- 15% (P < 0.05).
      We conclude that increased hypoxic tolerance is abolished by N-methyl-D-aspartate
      (NMDA)-antagonists but not non-NMDA-antagonists.

PMID- 8878113
TI  - State-dependent changes of extracellular glutamate in the medial preoptic area in
      freely behaving rats.
AB  - Microdialysis technique was applied to the medial preoptic area (mPOA) of the
      hypothalamus, a crucial site for the regulation of sleep, in order to analyze the
      interrelationship between the extracellular level of glutamate (Glu) and the
      vigilance states. Dialysates from the mPOA were sampled at 5-min intervals for 2
      h diurnal period with a perfusion rate of 2.0 microliters/min in freely moving
      rats, whose sleep-waking behaviors were polysomnographically monitored.
      Extracellular Glu increased during wakefulness, exhibiting a peak at the
      transition period from wakefulness to non-rapid-eye-movement sleep (NREMS) (18.0%
      above the average), whereas it decreased during NREMS (9.2% below the average).
      It is likely that Glu in the mPOA is dynamically involved in the alterations of
      the vigilance states.

PMID- 8878114
TI  - Effect of a pyridinium metabolite derived from haloperidol on the activities of
      striatal tyrosine hydroxylase in freely moving rats.
AB  - The effects of a pyridinium metabolite (HPP+) derived from haloperidol (HP) on in
      vivo tyrosine hydroxylation was evaluated in freely moving rats. As an index of
      the in vivo activity of tyrosine hydroxylase (TH), the rat striatum was perfused
      with NSD-1015, and extracellular 3,4-dihydroxyphenylalanine (DOPA) levels were
      measured. HPP+ (1 mM) gradually reduced tyrosine hydroxylation to 30% of the
      basal level, although the effect was less potent than 1-methyl-4-phenylpyridinium
      ion (MPP+). On the contrary, HPP+ at a 0.1 mM dose decreased in 5
      hydroxyindoleacetic acid (5-HIAA) level, but did not affect dopamine metabolites.
      The present study revealed that HPP+ irreversible inhibited in vivo tyrosine
      hydroxylation by the same manner of MPP+. However, the neurotoxic effects of HPP+
      in vivo would be selective for serotonergic over dopaminergic neurons, which
      distinguishes the toxic profile of this compound compared to that of MPP+.

PMID- 8878115
TI  - Muscarinic activation reduces changes in [Ca2+]o evoked by stimulation of
      Schaffer collaterals during blocked synaptic transmission in rat hippocampal
      slices.
AB  - The rat hippocampal slice preparation and blockers of postsynaptic glutamate
      receptors (6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX) 10 microM; DL
      2-amino-5-phosphonovaleric acid (APV) 30 microM) were used to study the effects
      of muscarinic activation on stimulus-induced decreases in [Ca2+]o presumably due
      to presynaptic Ca-influx. Perfusion with carbachol (100-200 microM) transiently
      reduced these changes in [Ca2+]o. Blockade of this muscarinic effect by
      pirenzepine (200 microM) and prolongation of this effect after prolonged lithium
      (1 mM) incubation suggest involvement of the muscarinic M1 receptor subtype.
      These findings suggest, that activation of M1 receptors might contribute to
      inhibition of excitatory synaptic transmission by inhibiting presynaptic Ca
      influx. In this way, the muscarinic enhancement of excitatory input may be
      limited to non-deleterious levels.

PMID- 8878116
TI  - Focal brain stimulation in healthy humans: motor maps changes following partial
      hand sensory deprivation.
AB  - Cortical motor maps of first dorsal interosseus (FDI), abductor digit minimi
      (ADM) and wrist flexors muscles were produced following transcranial focal
      magnetic stimulation of the contralateral motor areas in seven volunteers. Motor
      evoked potentials (MEPs) were recorded before and during median and radial nerves
      anaesthetic block at wrist. Results indicated that the FDI muscle cortical
      representation was significantly reduced; this muscle was entirely "enveloped' in
      the hand region deprived of its cutaneous sensory information, despite
      maintaining its usual proprioceptive feed-back and strength via the ulnar nerve.
      On the contrary, the ADM (serving as "control condition' because outside the
      anaesthetised hand area) cortical representation was unchanged, even if showing a
      tendency to enlarge in the topographic maps. No amplitude changes of compound
      muscle action potentials of ADM and FDI during peripheral stimulations were
      observed, while changes in F-wave responses were detected in both muscles. No
      significant topographic changes were found for the wrist flexors muscles. A
      possible explanation for these "short term' rearrangements of brain motor maps is
      given on the basis of neural plasticity mechanisms due to the loss of tonic
      cutaneous inputs on cortical and spinal motoneurons.

PMID- 8878117
TI  - Comparable amyloid beta-protein (A beta) 42(43) and A beta 40 deposition in the
      aged monkey brain.
AB  - Two distinct species of amyloid beta-protein (A beta), A beta 42(43) and A beta
      40, are deposited in the brains of patients with Alzheimer's disease and normal
      aged individuals. A beta 42(43), the long tailed A beta, is the initially and
      predominantly deposited species in senile plaques. Deposition of A beta is also
      observed in the aged monkey brains. We investigated the A beta species in the
      aged monkey brains immunocytochemically using monoclonal antibodies that
      discriminate between the C-termini of A beta 42(43) and A beta 40. We report here
      that A beta 40 as well as A beta 42(43) deposit in various types of senile
      plaques, including diffuse plaques of the aged monkey brain and that the ratio of
      A beta 40 to A beta 42(43) is higher compared with that in human brain.

PMID- 8878118
TI  - Species differences in functions of dopamine transporter: paucity of MPP+ uptake
      and cocaine binding in bovine dopamine transporter.
AB  - Expression of cloned cDNA for human, rat and bovine dopamine transporter (DAT) in
      COS cells allows the comparison of the functional differences among the
      respective dopamine transporters. Human DAT showed the highest activities for
      dopamine uptake, MPP+ uptake and cocaine binding, indicating that humans are more
      vulnerable to 1-methyl-4-phenylpyridinium (MPP+) toxicity and cocaine addiction.
      However, bovine DAT showed poor MPP+ uptake and cocaine binding, even though its
      dopamine uptake ability was quite avid. Here, we conclude that the paucity of
      MPP+ uptake and cocaine binding is a unique characteristic in bovine DAT.

PMID- 8878119
TI  - Postural responses to vibration of neck muscles in patients with unilateral
      vestibular lesions.
AB  - Postural responses to vibration applied unilaterally to dorsal neck muscles were
      recorded with a sway platform in nine patients with unilateral vestibular lesions
      and 19 normal subjects. In normals, the vibration induced a forward postural
      deviation. In patients, vibration of the neck contralateral to the lesion induced
      normal forward sway, whereas ipsilateral vibration resulted in sway of lower
      amplitude than normal and predominantly in the direction of the lesion or
      backwards. It is suggested that the proprioceptive error signal introduced by the
      neck vibration combined with an asymmetrical vestibular input due to a unilateral
      vestibular lesion provoked an erroneous representation of head position in
      patients resulting in a redirection of their body sway.

PMID- 8878120
TI  - Postural stability of the head in response to slowly imposed, small elastic
      loads.
AB  - To examine postural stability of the head, slow, undetectable rotations of small
      amplitude were imposed about a vertical axis while human subjects maintained a
      stationary body. Six normal subjects were used. The rotations were imposed
      through an elastic linkage, and lasted 4 s. The amplitude of head rotation was
      small, approximately 0.002 rad. The imposed perturbations commenced from an
      unloaded resting position with the head facing forward, under four conditions (1)
      relaxed, eyes closed; (2) relaxed, eyes open; (3) still, eyes closed; and (4)
      still, eyes open. The terms "relaxed' and "still' refer to the prior instructions
      given to the subjects regarding how they were to hold their head. There was a
      near linear relationship between average torque and average head angle. The
      effective stiffness of the head on the neck was notably low, approximately 10 Nm
      rad-1. Two-way analysis of variance (ANOVA) demonstrated ability to increase mean
      stiffness between "relaxed' and "still' conditions by 51% (P < 0.02). Visual
      input did not change mean stiffness significantly. Therefore, for the rotations
      to have been imperceptible, either the visual shifts involved must have been
      imperceptible, or the eyes must have counterrotated.

PMID- 8878121
TI  - Secretoneurin-induced in vitro chemotaxis of human monocytes is inhibited by
      pertussis toxin and an inhibitor of protein kinase C.
AB  - The sensory neuropeptide secretoneurin (SN) triggers chemotactic migration of
      monocytes. We have investigated the possibility that SN, like other
      chemoattractants such as formyl-Met-Leu-Phe and chemokines, might stimulate
      migration of monocytes by G protein and protein kinase C (PKC) activation and
      induce Ca2+i release. We report that preincubation of monocytes with pertussis
      toxin inhibited SN chemotaxis. Staurosporine, an inhibitor of PKC, significantly
      decreased SN-induced chemotaxis of monocytes, suggesting that PKC may be involved
      in the signaling. Tyrphostin-23, which inhibits tyrosin kinase, did not affect SN
      induced chemotaxis of monocytes. This suggests that SN uses a signaling mechanism
      that is coupled to pertussis toxin-sensitive G proteins. Involvement of
      phospholipase C beta as a result of PKC activation is suggested by a SN-induced
      increase of intracellular Ca2+ concentration in monocytes.

PMID- 8878122
TI  - The role of the physicist in nuclear medicine.

PMID- 8878123
TI  - Complications and difficulties in radiolabelling blood cells: a review.
AB  - The radiolabelling of blood cells is occasionally problematical. Difficulties
      occur either with the labelling process itself or after the labelled cells have
      been reinjected. Failure to label may be due to pharmaceutical factors, such as
      difficulties with collecting sufficient cells, sedimentation problems or
      instability of the cell chelator, or problems may arise which are patient
      related, such as patient medication or the presence of disease. A number of
      surveys have been undertaken to assess the possibility of drug interference as a
      cause of problems with labelling or biodistribution. Leukocyte labelling
      difficulties occurred in patients who were on multi-drug therapy whose drug
      regimes included combinations of prednisolone, azathioprine, cyclosporin,
      ranitidine, nifedipine, cyclophosphamide and naproxen. While a direct causal
      relationship has not been established, the known adverse effects of the drugs on
      white cell function and kinetics suggest that patient medication could be an
      important factor in leukocyte labelling. Red cell labelling difficulties have
      occurred from time to time and published reports implicate pharmaceutical
      factors, such as choice of anti-coagulant, level of stannous ion and oxidation of
      technetium-99m (99Tcm). Patient-related factors such as the presence of disease
      or drugs have also been implicated. A survey of red cell problems and patient
      medication showed that difficulties occurred in patients who were treated with
      combinations of nifedipine, etoposide, idarubicin and cefataxime. In-vitro
      testing of a number of drugs with 99Tcm-labelled red cells has demonstrated that
      cyclosporin, nifedipine, verapamil, hydralazine, propranolol, digoxin and Teflon
      cannulae can affect labelling.

PMID- 8878124
TI  - Stress-reinjection 201Tl scintigraphy without redistribution imaging: prediction
      of the effect of coronary artery bypass grafting on regional myocardial 201Tl
      uptake.
AB  - Reinjection of thallium-201 (201Tl) improves the detection of myocardial
      ischaemia in approximately 50% of irreversible defects present on 3 h
      redistribution images. Additional reinjection studies, however, may limit the
      capacity of the nuclear laboratory and they are not patient-friendly Previous
      studies have suggested that only severe persistent defects with less than 50% of
      maximal 201Tl uptake are irreversibly damaged, with little chance of recovery
      following coronary artery bypass grafting (CABG). We examined the ability of a
      modified stress-reinjection protocol without redistribution imaging to predict
      subsequent improvement in myocardial perfusion post-CABG. Thirty-seven patients
      underwent quantitative planar stress/3 h reinjection 201Tl scintigraphy before
      and after uncomplicated CABG. After stress, segments were classified as normal (>
      or = 75% maximum 201Tl uptake), moderate defect (50-75%) or severe defect (<
      50%). After reinjection, they were classified as completely normalizing (> or =
      75%), partially improving moderate defect (increase > or = 10% but < 75%),
      partially improving severe defect (increase > or = 10% but < 50%), persistent
      moderate defect (< 10% increase) or persistent severe defect (< 50% initial
      uptake with < 10% increase). Scintigraphic classification was compared with left
      ventricular wall motion and post-operative classification. Of 336 initial stress
      defects, 264 (79%) were moderate defects and 72 (21%) were severe defects. After
      reinjection, 146 (55%) moderate defects normalized, 25 (9%) improved partially
      and 93 (35%) persisted. Nineteen (26%) severe defects normalized, 33 (46%)
      improved to become moderate defects, 7 (10%) improved only slightly and 13 (18%)
      persisted. Post-CABG, 201T1 uptake was normal in 123 of 146 (84%) completely
      normalizing moderate defects, 15 of 25 (60%) partially improving moderate
      defects, 53 of 93 (57%) persistent moderate defects, 11 of 19 (58%) completely
      normalizing severe defects and 13 of 33 (39%) partially improving moderate
      defects. None of the partially improving severe defects or persistent severe
      defects normalized. The sensitivity and specificity of detection of viability
      with pre-CABG stress-injection scintigraphy were 66% and 72% respectively, with
      pre-CABG wall motion 80% and 40% respectively, whereas in combination they
      resulted in a sensitivity and specificity of 94% and 70% respectively. We
      conclude that stress/3 h reinjection without redistribution imaging is a
      clinically feasible method for predicting myocardial 201T1 uptake post-CABG. The
      severity of defects and the pattern of change of uptake after stress-injection
      are related to the likelihood of normal 201T1 uptake post-CABG. Severe defects
      after reinjection are very unlikely to recover.

PMID- 8878125
TI  - The use of GTN to improve the detection of ischaemic myocardium using 99Tcm
      tetrofosmin.
AB  - Recent work has shown that rest 99Tcm-sestamibi uptake may underestimate the
      amount of perfused myocardium, suggesting infarct tissue in some instances when
      myocardium is hypoperfused but which will benefit from revascularization.
      Administration of nitrates before a resting 99Tcm-sestamibi injection has been
      shown to increase tracer uptake. We have used 99Tcm-tetrofosmin as a myocardial
      perfusion agent and imaged 30 patients at stress, rest and again at rest
      following administration of sublingual nitrates. All patients had
      angiographically demonstrated severe coronary artery disease and 27 patients had
      previous infarction. Twenty-one patients were stressed on a treadmill and nine
      using intravenous dobutamine. Images were analysed using both a visual and semi
      quantitative analysis. Defects were observed in 39 coronary artery territories on
      stress 99Tcm-tetrofosmin imaging, 23 appearing fixed on standard rest imaging.
      Twelve (52%) of these defects showed reversibility on rest with glyceryl
      trinitrate (GTN) imaging and increased reversibility was seen in 62% of defects
      reversible at rest. We conclude that, in patients with severe coronary artery
      disease and fixed rest defects, GTN given prior to the rest injection appears to
      improve the detection of ischaemic hypoperfused myocardium.

PMID- 8878126
TI  - Fatty acid metabolic imaging with 123I-BMIPP for the diagnosis of coronary artery
      disease: application to patients with diabetes mellitus and hyperlipidaemia.
AB  - The aim of this study was to assess the relation of plasma substrate
      concentration to 123I-beta-methyliodophenyl-pentadecanoic acid (123I-BMIPP)
      kinetics in the myocardium and to test the application of 123I-BMIPP imaging to
      patients with diabetes mellitus (DM) and/or hyperlipidemia (HL). 123I-BMIPP
      imaging was performed on 78 patients with suspected coronary artery disease, 22
      with HL, 11 with DM, 12 with HL and DM, and 33 with neither HL or DM. Significant
      coronary stenosis (defined as > or = 50% of luminal diameter) was documented in
      49 patients. After an overnight fast, blood samples were drawn for blood glucose,
      insulin, cholesterol, triglycerides and free fatty acid levels. Then, 148 MBq
      123I-BMIPP was injected intravenously and flushed rapidly with saline. Data were
      obtained for 60s in a standard anterior projection in list mode, at a rate of 1
      frame per second. Myocardial single photon emission tomographic (SPET) images
      were obtained 20 min and 4 h post-injection. The myocardial uptake of 123I-BMIPP
      was calculated using the Ishii-MacIntyre method. Regional accumulation of 123I
      BMIPP was scored semi-quantitatively from 0 (normal) to 4 (no activity), and the
      sum of regional scores in each patient was defined as the total defect score
      (TDS). Myocardial uptake and clearance of 123I-BMIPP had no relation to the
      levels of blood glucose, insulin, cholesterol, triglycerides or free fatty acids.
      Myocardial uptake and clearance of 123I-BMIPP, TDS and the sensitivity of
      detecting significant coronary stenosis were not significantly different between
      the four groups of patients. We conclude that 123I-BMIPP can be used to detect
      impaired fatty acid metabolism in patients with diabetes mellitus and/or
      hyperlipidaemia.

PMID- 8878127
TI  - Quantitative salivary gland scintigraphy in the diagnosis of parenchymal damage
      after treatment with radioiodine.
AB  - This study was undertaken to quantify salivary gland parenchymal damage after
      radioiodine treatment with a standard protective regimen of ascorbic acid.
      Altogether, 106 patients underwent quantitative salivary gland scintigraphy with
      99Tcm-pertechnetate prior to and 3 months after radioiodine therapy. Parenchymal
      function was quantified by calculating 99Tcm-pertechnetate uptake 13 min post
      injection. Patients received 131I doses ranging from 400 MBq to 24 GBq
      (cumulative). Among the patients who received large doses of 131I, severe
      parenchymal destruction could be visually analysed as well as quantitatively
      evaluated. In contrast, after low-dose radioiodine treatment, mild parenchymal
      impairment was demonstrated by quantitative evaluation only. In conclusion,
      standardized quantitative salivary gland scintigraphy is essential for the
      reliable detection of mild parenchymal malfunction. Despite the standard
      protection regimen using ascorbic acid as a sialogogue, radioiodine therapy
      induces loss of salivary gland parenchymal function even with low doses of 131I.

PMID- 8878128
TI  - Assessment of completeness of thyroid ablation by estimation of neck uptake of
      131I on whole-body scans: comparison of quantification and visual assessment of
      thyroid bed uptake.
AB  - Thyroid cancer is treated by thyroidectomy followed by radioiodine ablation of
      the residual active tissue in the thyroid bed. Completeness of ablation can be
      assessed from neck images of whole-body 131I scans by visual estimation or
      quantitative analysis By visual assessment, ablation can be considered complete
      if there is no uptake in the neck or the uptake is empirically considered too
      small. By quantification, ablation is considered complete if neck uptake is < 1%.
      Further radioiodine therapy is considered necessary only if neck uptake exceeds
      1% of the administered dose. Both visual assessment and quantification of thyroid
      bed uptake were applied to 46 scans after diagnostic or therapeutic doses of 131I
      had been administered to 25 patients who were being followed up for follicular or
      papillary carcinoma of the thyroid. The results were compared to assess the
      effect of either method on determining the need for a further ablative dose of
      131I. Visual assessment overestimated thyroid bed uptake in 10 of 46 (22%) of the
      scans. Bearing in mind the unpleasantness of radioiodine ablation and the
      potential for bone marrow toxicity, it is recommended that quantification of neck
      uptake should be routinely performed as a guide to completeness of ablation and
      to determine the need for a therapeutic dose of the isotope. This should help to
      avoid unnecessary radioiodine treatment in patients with thyroid cancer.

PMID- 8878129
TI  - Evaluation of external radiation exposure rate from radioiodine-treated
      hyperthyroid patients and radiation safety considerations.
AB  - Hyperthyroid patients treated with radioiodine (131I) pose an external radiation
      risk to individuals who come into close contact with them. In order to determine
      changes in levels of external radiation with time in relation to the dose
      administered, 38 hyperthyroid patients being treated with 131I were evaluated
      Thyroid uptake, plasma T3, T4 and TSH levels were measured prior to treatment.
      Using a Geiger-Muller probe, levels of external radiation were measured at
      distances of 0.3, 0.6, 1.0 and 2.0 m from the patient -at the level at which the
      maximum activity was recorded -30 min, 1, 3, 7 and 10 days post-therapy. The
      patients were split into two groups. Group I comprised 22 patients treated with <
      or = 370 MBq 131I, 5 (23%) of whom registered > 0.46 mC kg-1 at a distance of 1.0
      m 30 min post-therapy. Group II comprised 16 patients treated with > 370 MBq
      131I, 13 (81%) of whom registered 0.46 mC kg-1 at a distance of 1.0 m one day
      post-therapy. At 3 days in Group I and 7 days in Group II, the estimated total
      radiation exposure rates were found to exceed the 1994 US Nuclear Regulatory
      Commission dose limits for children and pregnant women. Based on the results
      obtained, we present some guidelines intended to prevent the public from
      unnecessary radiation exposures.

PMID- 8878130
TI  - 99Tcm-HMPAO brain SPET in patients with pseudotumour cerebri.
AB  - The aim of this study was to look for regional cerebral blood flow (rCBF)
      abnormalities in patients with a recent diagnosis of pseudotumour cerebri (PTC)
      and to compare 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) cerebral
      single photon emission tomographic (SPET) findings with those of X-ray computed
      tomography (CT) and magnetic resonance imaging (MRI). Seventeen consecutive
      patients aged 14-50 years (mean = 29 years) without previous drug treatment for
      PTC underwent 99Tcm-HMPAO SPET, cranial CT and MRI studies. No patient had
      evidence of intracranial mass lesions on the CT or MRI scans. Qualitative
      analysis of the 99Tcm-HMPAO SPET studies revealed impaired rCBF in nine (53%)
      patients. The CT and MRI studies revealed an empty sella in two patients, dural
      sinus thrombosis in one and a slit ventricle in another. Eight of the 13 patients
      with normal CT and MRI results had rCBF abnormalities. In contrast, three
      patients with CT and MRI abnormalities had a normal 99Tcm-HMPAO scan. Our results
      suggest that patients with PTC have functional abnormalities that are revealed by
      99Tcm-HMPAO brain SPET.

PMID- 8878131
TI  - Reduction of 123I-iomazenil uptake in haemodynamically and metabolically impaired
      brain areas in patients with cerebrovascular disease.
AB  - Iomazenil is a specific ligand for central-type benzodiazepine receptors (BZR).
      In order to determine the clinical significance of the findings of 123I-iomazenil
      single photon emission tomography (SPET) in cerebrovascular disease (CVD), we
      compared the cerebral uptake of 123I-iomazenil with oxygen metabolism measured by
      positron emission tomography (PET). Depending on the severity of the haemodynamic
      and/or metabolic impairment based on our institutional criteria [a reduction of <
      30.6 ml 100g-1 min-1 in cerebral blood flow (CBF) and an increase of > 0.52 in
      the oxygen extraction fraction (OEF)], the cortical areas were classified into
      four groups as follows: Group I, normal CBF and OEF; Group II, normal CBF and
      increased OEF; Group III, reduced CBF and normal OEF; Group IV, reduced CBF and
      increased OEF. Seven patients (mean age 65 +/- 7 years) with CVD underwent both
      PET and 123I-iomazenil SPET within 8 days. The ratios of the mean counts in 14
      regions of interest in the cerebral cortices to those in the cerebellar cortices
      (R/C ratios) were compared with the cerebral metabolic rate of oxygen (CMRO2).
      The R/C ratios of Group IV were lower than those of Group I (P < 0.005). The R/C
      ratios correlated with CMRO2 in Group III (r = 0.577, P < 0.01) and in Group IV
      (r = 0.707, P < 0.005), but not in Groups I or II. These results suggests that
      reduced uptake in 123I-iomazenil SPET reflects oxidative hypometabolism causing
      neuronal damage in haemodynamically and metabolically impaired areas in patients
      with CVD. This information may be valuable when deciding therapeutic approaches.

PMID- 8878132
TI  - Parathyroid imaging with 99Tcm-tetrofosmin.
AB  - The aim of this study was to evaluate whether 99Tcm-tetrofosmin is a suitable
      agent for parathyroid scintigraphy. Ten patients with hyperparathyroidism and two
      normal subjects underwent parathyroid scintigraphy with both 99Tcm-tetrofosmin
      and 201TI. Thyroid image subtraction was performed with 99Tcm-pertechnetate. In
      the 10 patients with hyperparathyroidism, the scintigraphic results were compared
      with the surgical findings, which showed seven parathyroid adenomas, two
      parathyroid adenomas with a co-existing thyroid adenoma, and one thyroid
      carcinoma. Both 99Tcm-tetrofosmin and 201T1 revealed eight true-positive results,
      one false-negative results and one false-positive result, with concordance in 8
      of 10 patients. The image quality with 99Tcm-tetrofosmin of both the raw and
      99Tcm-pertechnetate subtracted images was always superior compared with that with
      201T1. On the basis of the diagnostic results and the favourable dosimetric
      characteristics, we conclude that 99Tcm-tetrofosmin is a suitable agent for
      parathyroid scintigraphy.

PMID- 8878133
TI  - Symmetry of bone mineral density in the hips is not affected by age.
AB  - To assess the symmetry of bone mineral density (BMD) of the hips, we used dual
      photon absorptiometry (DPA) to asses BMD in 266 normal Chinese women in the
      bilateral femoral neck, trochanter and Ward's triangle regions. Linear regression
      analysis of the results showed excellent correlation between the hips. The
      correlation coefficients for the femoral neck, trochanter and Ward's triangle
      regions were 0.899, 0.892 and 0.935 respectively, and the standard errors of the
      estimate (S.E.E.) were 0.029, 0.027 and 0.022 g cm-2 respectively. Pooling the
      BMD data of corresponding regions (n = 532), the correlation coefficient was
      0.813 for femoral neck versus trochanter, 0.889 for femoral neck versus Ward's
      triangle, and 0.833 for trochanter versus Ward's triangle. Further analysis
      showed mean correlation coefficients of 0.854 for elderly subjects (age > or = 65
      years, n = 51) and 0.887 for younger subjects (age < 65 years, n = 215). In
      conclusion, assessment of left or right hip BMD may be used to represent the BMD
      of the contralateral hip and can reduce both the cost and radiation exposure
      during mass screening for osteoporosis.

PMID- 8878134
TI  - Design and assessment of a scintigraphy-guided biplane localization technique for
      breast tumours: a phantom study.
AB  - The aim of this study was to design and assess a scintigraphy-guided stereotaxic
      localization technique for breast phantoms. We wished to develop and validate
      scintigraphically aided biopsy of non-palpable breast masses identified only by
      sestamibi scintimammography. A biopsy table was built for patients to lie prone
      with the breast in a dependent position. The breast can be compressed in the
      cranial and caudal directions by fenestrated paddles. Three freely adjustable
      radioactive reference lines, placed along the x, y and z axes, each containing
      about 30 MBq (800 micro Ci) 99Tcm, were mounted on sliding rules on the external
      frame which surrounded the phantom. The breast phantom was a semi-square-shaped
      sponge. Background activity was provided by a sponge cloth containing 37 MBq (1
      mCi) 99Tcm solution. Non-palpable lesions were carved out of the same sponge and
      wrapped in thin plastic film, and labelled with about 11 MBq (300 microCi) 201T1.
      The lesions, 3-15 mm in size, were placed at random at phantom depths of 2-6 cm
      by an individual different from the person performing the localization.
      Scintigraphy-guided three-dimensional localization of the lesion was performed by
      acquiring two orthogonal images and superimposing the reference bars over the
      lesion image and thus identifying the exact x, y and z coordinates of the lesion.
      Using these coordinates, a 22 gauge needle, containing about 37 MBq (1 mCi) 99Tcm
      within its lumen, was stereotactically placed into the phantom, and the tracer
      contained in the needle injected into the lesion. Needle placement was primarily
      guided by the exact coordinates, but also by real-time visualization of the
      radioactive needle. Pre- and post-localization images were acquired and regions
      of interest (ROIs) defined. Also after the tracer was injected into the lesion,
      images of the phantom with and without the lesion were obtained to calculate the
      percentage of tracer injected outside the lesion. The results of 30 consecutive
      localization attempts included 25 exact localizations with less than 20% tracer
      injected outside the lesion, 2 "near misses' with 37-44% injected outside the
      lesion, and 3 "misses' with 60, 85 and 100% of the tracer being injected outside
      the lesion. The missed localizations were all in lesions at least 4 cm deep, and
      all had partially superimposed ROIs, which indicates the needle came very close
      to the lesion. To conclude, our scintigraphy-guided biplane localization
      technique for breast phantom lesions successfully localized 90% of all lesions.

PMID- 8878135
TI  - Standardization of a technique for BrIDA cholescintigraphy.
AB  - Calculation of ejection fraction by cholescintigraphy is a well-established
      technique to quantify motor function of the gallbladder. All previous
      cholescintigraphic studies of gallbladder emptying have exclusively used the
      anterior projection for gallbladder visualization. This may lead to inaccuracies
      because attenuation of gamma rays may vary depending on the state of gallbladder
      filling and body habitus. The use of geometric means may prevent these errors. In
      this study, 7 health volunteers were examined after the administration of 150 MBq
      99Tcm-bromotrimethyl-IDA (99Tcm-BrIDA) without any stimulus and 9 volunteers
      ingested a maxied, fatty meal 35-40 min after BrIDA injection. Imaging was done
      using a dualheaded camera in a dynamic study of 140 one-minute frames. A plateau
      of activity was reached between 70 and 90 min post-injection of BrIDA and between
      55-60% of maximal counts were achieved in the gallbladder region of interest
      (ROI) between 35 and 40 min. Significant emptying was seen in all nine subjects
      after the meal. No significant difference in ejection fraction was seen between
      the anterior projection and the geometric mean of the data from the anterier and
      posterior projections. The slope of the gallbladder filling curve from the
      anterior camera data was different from that obtained from the geometric mean,
      but the correlation coefficient was not significantly different. In conclusion,
      adequate counts are achieved in the gallbladder ROI 35-40 min after BrIDA
      injection, when the stimulus can be administered to study gallbladder emptying.
      There is no advantage to imaging in the anterior and posterior projections and
      data obtained from the anterior projection alone are adequate for gallbladder
      emptying studies.

PMID- 8878136
TI  - Energy metabolism in portal hypertension in children.
AB  - This study was designed to assess resting energy expenditure (REE) and
      nutritional status in children with hepatic and prehepatic portal hypertension in
      comparison with healthy controls. Twenty-five patients with portal hypertension
      (PHT) and a history of variceal bleeding were compared with 14 healthy volunteers
      selected after matching for age and sex. PHT patients were allocated to one of
      two groups: 11 children with liver cirrhosis and/or chronic hepatitis, aged 14.0
      +/- 3.3 y (means +/- SD) or 14 children with extrahepatic portal vein
      obstruction, aged 12.3 +/- 2.8 y. The control group consisted of 14 healthy
      children, aged 14.0 +/- 1.8 y. REE (indirect calorimetry) assessed after an
      overnight fast was significantly higher in PHT patients than in controls when
      related to body mass (143.7 +/- 29.5 and 116.1 +/- 5.9 kJ/kg, respectively; p <
      0.004), lean body mass (168.0 +/- 28.9 and 146.4 +/- 14.1 kJ/kg, respectively; p
      < 0.02), and body surface area (7480 +/- 736 and 6590 +/- 567 kJ/1.73 m2,
      respectively; p < 0.001). The ratios of measured REE to basal energy expenditure
      calculated from standard equations (Schofield equations) indicated higher REE in
      PHT patients (102.24 +/- 6.90% and 93.54 +/- 4.47%, respectively; p < 0.001). Fat
      was the predominant source of energy in both PHT patients and controls; the
      percentage of nonprotein energy derived from carbohydrate oxidation was equaled:
      36.04 +/- 18.84% and 37.15 +/- 15.71%, respectively. Analysis of percentage of
      undernutrition in PHT patients and controls revealed significant differences (44%
      and 21%, respectively; p < 0.001). Children with PHT are susceptible to
      malnutrition and have elevated REE compared with healthy controls. Fat is the
      principal basal state oxidative substrate for patients with PHT and healthy
      children.

PMID- 8878137
TI  - Acute phase response and plasma carotenoid concentrations in older women:
      findings from the nun study.
AB  - This cross-sectional study investigated whether the acute phase response was
      associated with suppressed circulating levels of antioxidants in a population of
      85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the
      presence of an acute phase response, as defined by an elevation in the serum
      concentration of C-reactive protein. Serum concentrations of albumin, thyroxine
      binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma
      concentrations of carotenoids and alpha tocopherol. Results showed that the
      presence of an acute phase response was associated with (1) an expected
      significant decrease in the serum concentrations of albumin (p < 0.001) and
      thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in
      copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in
      the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta
      carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response
      was associated with decreased plasma levels of the antioxidants lycopene, alpha
      carotene, and beta carotene. This decrease in circulating antioxidants may
      further compromise antioxidant status and increase oxidative stress and damage in
      elders.

PMID- 8878138
TI  - Outcomes of continuous process improvement of a nutritional care program
      incorporating serum prealbumin measurements.
AB  - It has been reported that the risk of protein-calorie malnutrition (PCM) for
      hospitalized patient populations can be as high as 50%. Left undiagnosed. PCM can
      lead to serious consequences, including increased morbidity and mortality.
      Visceral protein albumin is the traditional laboratory indicator of PCM. In the
      past few years, however, several other visceral proteins have been lauded as
      superior markers. We undertook several studies to test the effectiveness of using
      one of these, prealbumin, as an aid in nutritional assessment. We found
      prealbumin to be a sensitive measure of nutritional status, allowing for earlier
      assessment and intervention, and thus reducing length of stay. Based on these
      findings, our hospital has generated and implemented a multidisciplinary
      nutrition care program that meets the 1995 Joint Commission on Accreditation of
      Healthcare Organizations Nutrition Care Standards. Prealbumin testing is an
      integral portion of this program; levels are determined on admission and repeated
      semi-weekly until discharge. Use of this program has led to improved patient care
      and financial benefit to the hospital.

PMID- 8878139
TI  - Influence of ingesting a solution of branched-chain amino acids on plasma and
      muscle concentrations of amino acids during prolonged submaximal exercise.
AB  - On two occasions, seven male endurance-trained cyclists performed sustained
      exhaustive exercise with reduced muscle glycogen stores. During exercise, the
      subjects were supplied in random order with an aqueous solution of branched-chain
      amino acids (BCAA) or flavored water (placebo). Ingestion of BCAA caused the
      concentration of these amino acids to increase by 135% in the plasma and by 57%
      in muscle tissue during exercise, whereas in the placebo trial there was no
      change or a slight decrease in the concentration in plasma and a decrease of 18%
      in the muscle. The plasma concentration of alanine increased by 48% during
      exercise when BCAA were ingested, and the increase in the muscle concentration of
      alanine during exercise was larger (70% versus 31% in the placebo trial),
      suggesting an increased rate of alanine production. Also, the plasma
      concentration of arginine increased by 14% during exercise when BCAA were
      ingested, whereas there was no change during exercise in the placebo trial. There
      was a smaller decrease in the muscle glutamate concentration during exercise in
      the BCAA trial (32% versus 47% in the placebo trial; p < 0.05), but, for the
      remaining amino acids, there was no difference between the BCAA and placebo
      trials. There was a significant decrease in the muscle glycogen concentration
      during exercise in the placebo trial, whereas only a small decrease was found in
      the BCAA trial (28 and 9 mmol/kg wet wt [p < 0.05] in the placebo and BCAA trial,
      respectively). This might indicate that an increased supply of BCAA has a sparing
      effect on muscle glycogen degradation during exercise.

PMID- 8878140
TI  - Preoperative assessment in cases of adult megacolon suffering from moderate
      malnutrition.
AB  - Acquired megacolon is a chronic disease associated with constipation and
      malnutrition. Surgical treatment may be required for the alleviation of the
      intestinal symptoms, emphasizing the interest of nutritional assessment in this
      population. In a prospective study of 33 patients suffering from acquired
      megacolon and requiring either anterior resection or pull-through operation,
      standard anthropometric and biochemical measurements as well as the PNI of Buzby
      and Mullen were preoperatively assessed. Mean age of the population was 49 +/- 13
      y, with 17 males and 16 females. The combined nutritional score indicated 63.6%
      of the population were malnourished (21/33) of the patients, whereas the
      Prognostic nutritional index (PNI) revealed 3 high-risk cases (9.1%), 9 with
      moderate risk (27.3%), and reduced risk for all others. Indeed, 39.4% (13/33) of
      the patients displayed surgical or septic problems. Chi-square analysis confirmed
      that both studied criteria were significantly associated with complications (p <
      0.05), as morbidity was restricted predominantly to cases with unfavorable
      Prognostic nutritional index (PNI) results or clear signs of nutritional deficit.
      Both PNI and conventinoal nutritional assessment are valuable tools for the
      screening of these surgical candidates. Artificial alimentation was not used in
      this experience, but deserves consideration in selected patients. Nutritional
      status improved in the late postoperative period, with normalization of bowel
      function.

PMID- 8878141
TI  - Dietary intake of community-based HIV-1 seropositive and seronegative injecting
      drug users.
AB  - Dietary intake was assessed in a subsample of a cohort of inner-city injecting
      drug users (IDUs). In this population of predominantly African-American IDUs,
      including both HIV -1-infected and noninfected men and women, a food frequency
      questionnaire (FFQ) and a 24-h recall were administered. One hundred seven
      volunteers participated. Although total caloric intake was consistently higher
      with the food frequency method, percent of total calories from fat, protein, and
      carbohydrates were similar between the FFQ and 24-h recall. Spearman's
      correlations for agreement between the 24-h recall and the FFQ ranged from 0.22
      for vitamin E to 0.52 for carbohydrates. HIV-1 seropositives reported higher
      protein (p = 0.05) and fat (p = 0.02) consumption than seronegatives according to
      the 24-h recall. The difference in total fat consumption was due to higher
      intakes of saturated and monounsaturated fats (p = 0.01). Median intakes of
      vitamins B2 and B12, pantothenic acid (p < or = 0.05), phosphorous (p < or =
      0.01), and selenium (p < or = 0.005) were also greater in HIV-1 seropositives.
      Reported intake of vitamins A and E, calcium, and zinc were below the recommended
      daily allowances for both HIV-1 seropositives and seronegatives. Although intakes
      of most nutrients appeared adequate for the group as a whole, extreme ranges were
      observed and may be the result of imbalanced food selections and day to day
      variation. Food group analysis indicated low intakes of fruits, vegetables, milk,
      and milk products. More research is needed to fully understand the implication of
      dietary habits and nutritional status in the free-living HIV-1-infected and
      noninfected IDUs.

PMID- 8878142
TI  - A comparison between oral and nasogastric nutritional supplements in malnourished
      patients.
AB  - There is a common perception that malnutrition is an inevitable manifestation of
      illness, that oral nutritional supplements are not taken or reduce the
      consumption of oral diet, and that nasogastric feeding is poorly tolerated. This
      study assessed the efficacy of supplemental enteral feeding on the nutritional
      status of malnourished patients, to compare oral supplements (OS) with overnight
      supplemental nasogastric feeding (NG) on nutritional status and to determine the
      effect of nutritional supplements on oral diet. Malnourished hospital patients
      were randomized to one of three groups: control (C), OS, or NG. All patients had
      access to hospital diet. Supplements were prescribed to meet estimated
      nutritional needs. Nutritional status was recorded at the start and the end of
      the feeding period. The total nutritional intake was recorded. Weight gain
      occurred in 64% of the supplemented patients, whereas 73% of the controls lost
      weight with mean weight changes of +2.9% OS. +3.3% NG, and -2.5% C. There was no
      difference in the mean energy intake from food in the three groups. There were no
      documented complications of OS and three minor complications of NG. Both methods
      of supplementation allow weight gain without significantly affecting spontaneous
      oral intake.

PMID- 8878143
TI  - Steatorrhea: a common manifestation in patients with HIV/AIDS.
AB  - Multiple infectious causes of diarrhea are known in patients with HIV/AIDS.
      Maldigestion and malabsorption have been reported in patients with HIV/AIDS and
      may be independent of infectious etiologies. Among ambulatory patients with
      HIV/AIDS, we examined the prevalence of fat malabsorption (steatorrhea). Sixty
      one patients with unexplained diarrhea (defined as > 2 stools/d) and/or weight
      loss despite adequate caloric intake (and without clinical evidence of chronic
      pancreatitis) were evaluated in our outpatient Gastroenterology-Nutrition Clinic
      between March 1, 1993, and July 1994. Patients were instructed by a dietitian to
      follow a > or = 100 g/d fat diet for 24 h before submitting a stool sample for
      qualitative (or quantitative) fecal fat determination. Forty-five patients, 32
      with ongoing diarrhea and 13 without diarrhea, submitted stool samples. Twenty
      two of 45 patients (49%) had qualitative or quantitative steatorrhea, 16/32 with
      diarrhea (50%) and 6/13 patients without diarrhea (46%). Thirty of 32 patients
      with diarrhea had had extensive microbiologic and/or endoscopic evaluations. Only
      9 patients had a detectable intestinal pathogen, 5 patients had cytomegalovirus
      (4 treated), 4 patients had cryptosporidia (3 treated), and 1 patient had
      microsporidia. Steatorrhea, as determined by abnormal qualitative fecal fat, is
      detectable in nearly 50% of patients with HIV/AIDS. Fat malabsorption appears to
      be a primary defect in these patients independent of detectable pathogens.
      Assessment of fat malabsorption should be considered in patients with unexplained
      weight loss or diarrhea before extensive evaluation for opportunistic infections.

PMID- 8878144
TI  - Serum zinc and protein levels: lack of a correlation in hospitalized patients
      with AIDS.
AB  - Abnormally low serum zinc levels are associated with advanced states of
      malnutrition. Zinc levels are thought to parallel serum albumin, and repletion of
      zinc has reportedly led to increased albumin. We examined the correlation between
      zinc deficiency and serum proteins in hospitalized patients with AIDS. Over 500
      inpatient consultations were performed by our Gastroenterology-Nutrition Consult
      Service from May 1992 to June 1994. We reviewed the medical records from all 228
      AIDS patients in whom a serum zinc level was measured (by atomic absorption
      spectrophotometry). The correlation between serum zinc, albumin, prealbumin, and
      transferrin drawn on the same hospital day was analyzed by linear regression. The
      patients were stratified by the level of albumin, group A albumin < 2.0 g/dL,
      group B albumin 2.0-2.9 g/dL, and group C albumin > 3.0 g/dL, to allow comparison
      of the incidence of diarrhea and mean zinc level by chi square. Thirty-four
      patients had more than one serum zinc and albumin determination; the change over
      time was compared by linear regression. Serum zinc and albumin, prealbumin, and
      transferrin levels did not correlate strongly (r2 < or = 0.01). Furthermore,
      changes in zinc over time did not correlate with parallel changes in serum
      albumin (r2 < or = 0.01). In patients grouped by albumin, the proportion of
      patients with diarrhea did not differ significantly. The mean zinc levels were
      also not statistically significantly different. Serum zinc levels do not strongly
      correlate with serum proteins in hospitalized patients with AIDS. Serial measures
      of zinc over time also do not correlate strongly with changes in albumin. The
      incidence of diarrhea was not significantly different in patients with
      hypoalbuminemia or hypozincemia when compared with patients with near normal
      albumin or zinc. The relationship between zinc and serum proteins in AIDS
      patients is not linear. Zinc deficiency should be assessed in patients
      independent of the serum albumin.

PMID- 8878145
TI  - Zinc levels and infections in hospitalized patients with AIDS.
AB  - Impaired cellular and humoral immunity and phagocytic function have been
      attributed to zinc deficiency. This study examined the association between low
      serum zinc concentration and opportunistic infections in hospitalized patients
      with the acquired immune deficiency syndrome (AIDS). We examined the records from
      all 505 inpatient consultations performed by our Nutrition Service from May 1992
      through June 1994. The medical records from all 228 patients with AIDS with known
      serum zinc levels (determined by atomic absorption spectrophotometry) were
      reviewed. The length of HIV seropositivity, most recent CD4 count, presence of
      diarrhea, and degree of malnutrition were noted. The principal diagnosis
      accounting for the admission was grouped according to the type of infection:
      Pneumocystis carinii pneumonia (PCP), viral, fungal, bacterial, and other. Sixty
      seven patients (29%) had abnormally low serum zinc levels (LSZ < 55
      micrograms/dL), 49 patients (21%) had borderline low serum zinc (BSZ > or = 55
      and < or = 65 microgram/dL), and 112 (49%) patients had normal serum zinc levels
      (NSZ > 65 micrograms/dL). There was no significant difference among the groups in
      CD4 count, length of HIV seropositivity, presence of diarrhea, or severity of
      malnutrition. Patients with zinc deficiency (LSZ) had a significantly higher
      incidence of bacterial infection than did patients with normal zinc. Patients
      with borderline zinc levels had an intermediate incidence of bacterial infection.
      There were no significant differences among the three groups in the incidence of
      PCP, viral, or fungal infections. Severe zinc deficiency was noted in 29% and
      borderline levels in an additional 21% of hospitalized AIDS patients. A low zinc
      level was not associated with the length of HIV seropositivity, CD4 count, or
      degree of malnutrition. Hypozincemia was associated with an increased incidence
      of concomitant systemic bacterial infections.

PMID- 8878146
TI  - Protein-energy status and 15N-glycine kinetic study of child a cirrhotic patients
      fed low- to high-protein energy diets.
AB  - In five male cirrhotic patients (Child A) and in four age- and sex-matched
      healthy control subjects, whole-body protein turnover was measured using a single
      oral dose of 15N-glycine as a tracer and urinary ammonia as end product. Subjects
      were studied in the fasting and feeding state, with different levels of protein
      and energy intake. The patients were underweight and presented lower plasma
      transthyretin and retinol-binding protein levels. When compared with controls,
      the kinetic studies showed patients to be hypometabolic in the fasting (D0) state
      and with the control diet [D1 = (0.85 g of protein/ 154 kJ) x kg-1.day-1].
      However, when corrected by body weight, the kinetic differences between groups
      disappeared, whereas the N-retention in the feeding state showed better results
      for the patients due mainly to their efficient breakdown decrease. When fed high
      level protein or energy diets [D1 = (0.9 g protein/195 kJ) and D3 = (1.56 g
      protein/158 kJ) x kg-1.day-1], the patients showed D0 = D1 = D2 < D3 for N-flux
      and (D0 = D1) < D3 (D2 is intermediary) for protein synthesis. Thus, the present
      data suggest that the remaining mass of the undernourished mild cirrhotic
      patients has fairly good protein synthesis activity and also that protein, rather
      than energy intake, would be the limiting factor for increasing their whole-body
      protein synthesis.

PMID- 8878147
TI  - Responses of insulin to oral glucose and fructose loads in marginally copper
      deficient rats fed starch or fructose.
AB  - The purpose of this study was to assess the effects of dietary fructose either
      alone or in combination with marginal copper deficiency in weanling male rats
      exposed to their respective diets for only 2 wk. This short duration of exposure
      to inadequate copper intake prevents progressive morbidity brought about by
      increasing periods of exposure to dietary copper deprivation. Weanling male rats
      were fed a copper-deficient (0.6 microgram Cu/g) or a copper-adequate (6.0
      micrograms Cu/g) diet containing 62% fructose or 62% starch for 2 wk. Either an
      oral glucose or an oral fructose tolerance test was conducted after an overnight
      fast. Insulin levels were elevated by either oral glucose or oral fructose at
      fasting and at 30 min postload in rats fed fructose compared with those fed
      starch. Despite high levels of plasma, insulin blood glucose was not reduced.
      Marginal copper deficiency had no effect on either plasma insulin or blood
      glucose. Data identify fructose as the sole agent responsible for inducing
      adverse changes in glucose metabolism. Two weeks of fructose consumption was
      sufficient to produce these changes.

PMID- 8878148
TI  - Oral arginine supplementation in acute liver injury.
AB  - Acute liver failure is accompanied by a high rate of bacterial and septic
      complications. Arginine has a potent effect on the immune system and modulates
      bacterial clearance in septic models. We studied the effect of oral arginine
      supplementation on the extent of liver injury and the associated bacterial
      translocation in an acute liver injury model in rats. Sprague-Dawley rats were
      divided into normal, liver injury, and arginine supplemented groups. In the
      arginine group, 2% arginine was supplemented daily through a nasogastric tube for
      8 d. Acute liver injury was induced on the eighth day by intraperitoneal
      injection of D-galactosamine (1.1 g/kg body wt). Samples were collected 24 h
      after the liver injury. In the arginine-supplemented group, alkaline phosphatase,
      bilirubin, and aspartate aminotransferase were reduced significantly compared
      with the acute liver injury control group. The results of bacterial translocation
      in the arginine-supplemented group showed a significantly reduced number of
      translocated bacteria to the liver and mesenteric lymph nodes than occurred in
      the acute liver injury group. The histological study of the liver in arginine
      supplemented group showed scattered areas of hepatocellular necrosis and
      inflammatory cell infiltration, and in the acute liver injury group there were
      more and widespread hepatocellular necrosis and inflammatory cell infiltration.
      Oral supplementation of arginine in an acute liver injury model improves
      significantly the state of the liver injury and reduces bacterial translocation
      to the liver and mesenteric lymph nodes.

PMID- 8878149
TI  - Increased lipid peroxidation and antioxidant activity in methionine-induced
      hepatitis in rabbits.
AB  - The liver is especially susceptible to the toxic effects of methionine due to its
      role in sulfur amino acid metabolism. Therefore, the excessive amounts of this
      amino acid may induce liver damage. To test the mechanisms of methionine-related
      hepatotoxicity, liver thiobarbituric acid reactive substances (TBARS), and
      activities of superoxide dismutase, catalase and selenium-dependent glutathione
      peroxidase were measured in rabbits fed a methionine-enriched diet for 6 or 9 mo.
      Morphological studies of livers were also made. Feeding rabbits the methionine
      enriched diet for 9 mo resulted in a significant increase in liver TBARS levels
      and antioxidant enzyme activities. Moreover, an inflammatory infiltration of
      portal triads in the treated rabbits were observed. These results indicate that
      methionine may induce hepatitis by increasing free radical processes.

PMID- 8878150
TI  - Severe hypophosphatemia related to refeeding.

PMID- 8878151
TI  - Hypophosphataemia: a dangerous disorder.

PMID- 8878152
TI  - Polyunsaturated fatty acid deficiency in liver diseases: pathophysiological and
      clinical significance.
AB  - Polyunsaturated fatty acid (PUFA) deficiency occurs in advanced cirrhosis and
      other liver diseases (acute hepatitis, cholestasis). Long-chain PUFA deficit in
      cirrhosis is due to both essential fatty-acid (EFA) deficiency and impaired PUFA
      biosynthesis. Although hepatic insufficiency itself mostly accounts for this
      phenomenon, other factors such as associated malnutrition also play a role. PUFA
      deficiency in cirrhosis probably has a wide array of both cellular and clinical
      consequences, but, at present, they have been difficult to prove. In addition,
      the route, dosage, and safety of PUFA supplementation in these patients needs
      extensive investigation in the future.

PMID- 8878153
TI  - Trace elements in the elderly.

PMID- 8878154
TI  - Continuous improvement of nutritional care is a multidisciplinary planned
      process.

PMID- 8878155
TI  - Serum zinc and protein status in AIDS patients.

PMID- 8878156
TI  - Fatigue during prolonged exercise.

PMID- 8878157
TI  - More attention on oral nutritional supplementation.

PMID- 8878158
TI  - Nutritional alterations in HIV-1 seropositive and seronegative drug users.

PMID- 8878159
TI  - Some basic observations concerning experimental cancer anorexia.

PMID- 8878160
TI  - Cost analysis in nutrition-intervention outcomes studies.

PMID- 8878161
TI  - Methods and criteria for nutritional epidemiology--in need of repair?

PMID- 8878163
TI  - Time to byte the bullet?

PMID- 8878162
TI  - Where's the payback for nutrition research?

PMID- 8878164
TI  - What dietitians need to know about managed-care implications for practice.

PMID- 8878165
TI  - Does undernutrition during infancy inhibit brain growth and subsequent
      intellectual development? 1963.

PMID- 8878166
TI  - Antioxidants in cardiovascular disease: randomized trials.
AB  - The hypothesis that antioxidant vitamins might reduce cardiovascular disease risk
      is based on a large body of both basic and human epidemiologic research. One of
      the most consistent findings in dietary research is that those who consume higher
      amounts of fruits and vegetables have lower rates of heart disease and stroke as
      well as cancer. Recent attention has focused on the antioxidant content of fruits
      and vegetables as a possible explanation for the apparent protective effects.
      Basic research provides a plausible mechanism by which antioxidants might reduce
      the risk of atherosclerosis. A large number of descriptive, case-control and
      cohort studies provide data suggesting that consumption of antioxidant vitamins
      is associated with reduced risks of cardiovascular disease. These data raise the
      question of a possible role of antioxidants, such as vitamins C and E, and beta
      carotene, in the primary prevention of cardiovascular disease but do not provide
      a definitive answer. Results from several large-scale randomized trials of
      antioxidant supplements are now available; however, results are not entirely
      consistent. The results of the major trials do not prove or disprove the value of
      antioxidant vitamins, nor do they incriminate them as harmful. They do, however,
      raise the possibility that some of the benefits from observational epidemiology
      may have been overestimated and that there may be some adverse effects. At this
      point randomized trial data are not yet sufficient to fully assess the risk-to
      benefit ratios for antioxidant supplements. More reliable data should be
      forthcoming in the near future which will better define the role of antioxidants
      in the primary and secondary prevention of atherosclerotic disease as well as
      cancer.

PMID- 8878167
TI  - Carbohydrate three-carbon metabolism of adipose tissue during surgery.

PMID- 8878168
TI  - Resting energy expenditure, weight loss, and altered body composition in HIV
      infection.
AB  - Failure to downregulate resting energy expenditure (REE) as an adaption to
      anorexia or malabsorption is often stated as the major cause of weight loss in
      individuals with AIDS. In a prospective study, REE was compared with weight
      changes in HIV-infected patients. The impact of altered body composition on REE
      was reassessed by critical review of the literature. Patients were 65 male HIV
      infected patients, 28 with recent weight loss (WL), and 37 who were weight stable
      (WS); 50/65 patients had AIDS, and 29/65 had acute infections; 29 male healthy
      persons served as controls. Indirect calorimetry, prospective intake protocol,
      and bioelectrical impedance analysis were performed. Absolute REE was lower in WL
      patients than in controls (1459 +/- 309 versus 1711 +/- 151 kcal/d, p < 0.001)
      and in WS patients (1625 +/- 402 kcal/d, p < 0.05). REE/kg body cell mass (BCM)
      was higher in WL and WS than in controls (both p < 0.01) due to lower BCM in both
      patient groups (p < 0.001). REE (%Harris-Benedict) was not different among the
      three groups. Weight changes around the measurement were not correlated to REE
      (r2 = 0.0008, p = 0.82). REE was independent of diarrhea, acute infection, fever,
      or caloric intake. REE had a stronger correlation to body weight and to Harris
      Benedict's prediction than to fat-free mass or BCM. REE explains < 1% of weight
      changes. Many patients can downregulate REE as an adaption to anorexia and/or
      malabsorption. Higher REE/kg BCM does not signify hypermetabolism at the cellular
      level but can be explained by the maintenance of energy-consuming visceral tissue
      within the BCM during BCM loss.

PMID- 8878169
TI  - Simultaneous measurement of albumin and fibrinogen synthetic rates in normal
      fasted subjects.
AB  - Albumin and fibrinogen synthesis appear to account for the majority of protein
      exported by the liver and therefore make a substantial contribution to that of
      whole-body protein synthesis. However, data on the protein synthetic rates of
      albumin and fibrinogen in normal subjects are limited. Albumin and fibrinogen
      synthetic rates were measured simultaneously over a 120-min period in normal
      subjects (n = 6) by using a flooding dose of 2H5-phenylalanine. Tracer
      incorporation into proteins was measured by gas chromatography/mass spectrometry.
      Body mass index, circulating concentrations of insulin, albumin, fibrinogen, C
      reactive protein, and plasma volumes of the subjects were all within the normal
      reference range. There was a small and transient rise in circulating insulin
      concentrations following the flooding dose of phenylalanine. The median
      fractional synthetic rate and absolute synthetic rate for albumin was 10.3%/d and
      208 mg.kg-1.d-1, respectively. The median fractional synthetic rate and absolute
      synthetic rate for fibrinogen was 19.5%/d and 28 mg.kg-1.d-1. In the context of
      the current interest in manipulating the inflammatory response of patients with
      various disease states, we introduce the concept of an acute phase protein
      quotient (APPQ). The APPQ is defined as the absolute rate of fibrinogen synthesis
      divided by that of albumin. In this group of normal subjects, the median APPQ was
      0.14.

PMID- 8878171
TI  - Fatty acid unsaturation increases expression and capping of murine lymphocyte
      CD44 and CD45.
AB  - We studied the effect of incubating murine lymphocytes with cis-unsaturated fatty
      acids on expression and capping of CD44 and CD45. Lymphocytes were incubated with
      stearic (18:0) or oleic (18:1 omega-9) acid bound to bovine serum albumin (BSA).
      After incubation with rat anti-CD44 or anti-CD45 monoclonal antibodies and then
      with fluorescent-labeled anti-rat antibody, mean fluorescence intensity (FI) was
      measured by using flow cytometry. Capping was measured after warning and fixation
      in paraformaldehyde. Steady-state fluorescence anisotropy (rs) was measured after
      the cells had been incubated with trimethylammoniumdiphenylhexatriene. Incubation
      with oleic acid, but not stearic acid or BSA alone, was associated with an
      increase in FI of CD44. Expression of CD45, however, was increased by both
      stearic and oleic acids to the same degree over BSA controls. CD44 and CD45
      capping were both increased by incubation with oleic acid. Rs was decreased in
      cells incubated with oleic acid, suggesting an increase in membrane fluidity. We
      conclude that incubation with oleic acid increases expression of CD44 and
      increases capping of both CD44 and CD45. These findings were confirmed in feeding
      experiments, in which rs was reduced and CD44 capping increased by
      polyunsaturated fatty acid diets.

PMID- 8878170
TI  - Nucleotide-free diet suppresses antigen-driven cytokine production by primed T
      cells: effects of supplemental nucleotides and dietary fatty acids.
AB  - Our previous studies suggest that nucleotides modulate T-helper (Th) cell
      mediated antibody (Ab) production. This nucleotide action is influenced by
      dietary fatty acids. Herein, we report the effects of nucleotide-free (NF) diets
      normal or high in saturated fatty acid on antigen-driven Th cell activation by
      using cytokine production as an indicator. C57BL/6 mice were fed a NF diet, a NF
      diet plus mononucleotide and nucleoside mixture (OG-VI), a NF diet high in
      saturated fatty acid (NF-SFA), or a NF-SFA diet plus OG-VI. Mice were then
      challenged with neoantigen, a keyhole limpet hemocyanin (KLH). Regional draining
      lymph nodes were collected 5-7 d following antigen (AG) priming, rechallenged
      with KLH in the culture, and resultant cytokine production was measured. IFN
      gamma and IL-5 production was lower in mice fed a NF diet at protein and mRNA
      levels. IL-4 and IL-2 mRNA expression was also lower in mice fed a NF diet. IFN
      gamma protein levels were higher in mice fed a NF-SFA diet than in mice fed a NF
      diet, but production of other cytokines was equally suppressed in those fed a NF
      SFA diet. In vivo OG-VI supplementation prevented aberrant cytokine production in
      mice fed a NF or NF-SFA diet. Polynucleotides added to the culture restored
      impaired IFN gamma and IL-5 production in mice fed a NF diet but did not further
      augment cytokine production in mice of other diet groups. These results indicate
      a potential role of nucleotides in Ag-driven Th-cell activation, and this
      nucleotide action is partly under the influence of dietary fatty acids.

PMID- 8878172
TI  - Overfeeding in a patient with Kwashiorkor syndrome.

PMID- 8878173
TI  - The physiology and brain mechanisms of feeding.
AB  - This article is designed as an introduction to the major theoretical models in
      the field of regulation of eating behavior, and a selective review of relevant
      neurobiological data. We first critically consider the paradigm of homeostasis as
      it relates to body energy content, and argue that additional theoretical
      constructs will be needed to account for the complexity of eating behavior in
      both nonhumans and humans. We then summarize some of the methods available to the
      neuroscientist in this area, and address some of their limitations. We review
      treatments and potential mechanisms that increase food intake, including
      deprivation, antimetabolites, norepinephrine, and several peptides including
      neuropeptide Y. We next review treatments that decrease food intake, including a
      variety of humoral, gastrointestinal, and pancreatic factors, as well as examine
      central pathways of satiety. This includes a discussion of leptin and other
      potential anorectic agents. We conclude with a discussion of human obesity and
      anorexias, and prospects for pharmacotherapy of eating disorders. We emphasize
      throughout that most regions of the human brain probably make some contribution
      to feeding behavior, and so a focus on any one area of transmitter/hormone is an
      unrealistic approach both in basic and applied areas.

PMID- 8878174
TI  - Role of adipose tissue in whole body metabolism.

PMID- 8878175
TI  - Metabolic abnormalities and the "wasting syndrome" in HIV infection.

PMID- 8878176
TI  - Dietary bioflavonoids, chalcones, and related alkenones in prevention and
      treatment of cancer.

PMID- 8878177
TI  - Special requirements for nutrition assessment in the aged.

PMID- 8878178
TI  - View from eastern Europe.

PMID- 8878179
TI  - Japan's efforts to control pharmaceutical expenditures and the convergence to a
      common path.

PMID- 8878180
TI  - Delivery of nutritional therapy: quality assurance of automated compounding
      devices.

PMID- 8878181
TI  - The dependence of tumor formation on the composition of the calorie-restricted
      diet as well as on the degree of restriction. 1945.

PMID- 8878182
TI  - Differential effects of fibronectin-derived oligopeptides on the attachment of
      rabbit lens epithelial cells in vitro.
AB  - Among the Arg-Gly-Asp (RGD)-containing sequences that are known to be cell
      binding domains of fibronectin, 500 migrograms/ml of Arg-Gly-Asp-Ser (RGDS) and
      Gly-Arg-Gly-Asp-Ser showed 100% inhibition of the attachment of cultured lens
      epithelial cells (TOTL-86 cells), when they were added to culture medium and
      coincubated with the cells for 24 h whereas RGD at concentrations of 500, 1,000
      and 2,000 micrograms/ml had no such activity. After 48 h of cocultivation of 800,
      400 or 200 micrograms/ml of RGDS with TOTL-86 cells, the percentage of floating
      cells was 100, 30.1 or 11.1%, respectively. After 144 h of cocultivation with
      RGDS, the percentage of floating cells was 1.6, 2.4 or 1.9%, respectively,
      indicating that RGDS was not cytotoxic to lens epithelial cells. However,
      replacing the medium with fresh medium containing new RGDS peptide resulted in
      floating of cells. We also studied the inhibitory effect of two other amino acid
      sequences that are found in cell-binding sites of the fibronectin molecule: Glu
      Ile-Leu-Asp-Val-Pro-Ser-Thr (EILDVPST) and Arg-Glu-Asp-Val (REDV). At 500 and
      1,000 micrograms/ml, respectively, neither EILDVPST nor REDV has an inhibitory
      effect on the attachment of TOTL-86 cells, while RGDS at a concentration of 500
      micrograms/ml completely inhibited the attachment of the cells in 24 h of
      incubation.

PMID- 8878183
TI  - Long-term development of lens opacities after exposure to ultraviolet radiation
      at 300 nm.
AB  - The long-term development of lens opacities after short-term exposure to
      ultraviolet radiation (UVR) was determined. Altogether, 200 Sprague-Dawley rats
      received unilaterally 5 or 20 kJ/m2 UVR (lambda MAX = 300 nm, lambda 0.5 = 10 nm)
      in vivo, during 15 min. At 1, 4, 8, 16 and 32 weeks after exposure subgroups of
      20 rats from each dose group were sacrificed. Both lenses were removed for
      measurement of intensity of forward scattered light. It was found that exposed
      lenses scatter light more than their contralaterals and that a higher dose
      induces more light scattering. After exposure to 5 kJ/m2, the mean difference in
      scattering remained unchanged between 1 and 32 weeks' latency, but the
      distribution of the individual differences in scattering became skew. For several
      animals, lens opacities induced by 5 kJ/m2 seemed to decrease during the
      observation period. Earlier observations in complement to current findings
      implicate that it is optimal to detect close-to-threshold UVR-induced cataract at
      1 week after exposure.

PMID- 8878184
TI  - Degradation of vimentin in frozen rat lenses.
AB  - Rat lenses stored for extended periods at -20 degrees C showed degradation and
      eventual disappearance of vimentin. This may have been caused by the rupture of
      cells and/or organelles by growing ice crystals and the subsequent release and
      diffusion of proteases. Besides the disappearance of vimentin there was also a
      decrease in the intensity of the beta B1 polypeptide after 3 months storage. The
      observations reported herein are generally qualitative in nature, but should
      serve to alert other investigators of a potential problem.

PMID- 8878185
TI  - Reassessment of the specificity of lens opacities in myotonic dystrophy.
AB  - Cataract has been considered for a long time one of the major indicators of the
      presence of the mutated myotonic dystrophy (DM) gene in asymptomatic relatives of
      DM patients. However, some recent studies show that not all cases of cataract
      typical of DM are associated with the disease even in members of DM families. In
      order to determine the frequency of lens opacities characteristic of DM in the
      general population and to evaluate the specificity of lens anomalies for
      detection of the DM premutation, we screened a sample of 1,400 random individuals
      for the presence of 'myotonic cataract'. Ten individuals were found with the
      typical lens opacities and no neuromuscular signs of DM; molecular analysis of
      the DM mutation showed that they all carried two normal alleles. Our data allow
      to conclude that bilateral cortical iridescent and posterior cortical lens
      opacities cannot be considered a marker of the presence of the DM premutation in
      the general population.

PMID- 8878186
TI  - Scheimpflug densitometric analysis of cataracts in diabetic rats: correlation
      with glycation.
AB  - Glycation has been implicated in cataract formation. Our earlier studies showed
      that crystallin glycation enhances oxidation and aggregation, whereas MIP26
      glycation affects the membrane permeability. Scheimpflug densitometric analysis
      has been used to quantify the lens opacification. In this study, we measured the
      progressive changes in lens opacification and correlated them with protein
      glycation in streptozotocin-induced diabetic rats. The lens opacification
      progressed in a biphasic manner: an initial slow increase between 0 and 60 days,
      followed by a steep increase between 60 and 90 days of diabetes. There was a
      strong correlation between lens opacification and lens crystallin and MIP26
      glycation. The correlation was relatively weak with plasma glucose. This study
      suggests that glycation of lens crystallin and MIP26 plays a significant role in
      the development of lens opacification in diabetic rats.

PMID- 8878187
TI  - Human cataract risk factors: significance of abstention from, and high
      consumption of, ethanol (U-curve) and non-significance of smoking.
AB  - Current ethanol consumption and cigarette smoking were quantified by
      questionnaire in Edinburgh and suburbs, Scotland, UK. Stringently matched
      cataract-control pairs (n = 990 and 858, respectively) were included. For
      ethanol, 'light and infrequent' consumption and 'light and frequent' were
      associated with a significantly lower risk of cataract than were total abstention
      and 'occasional' consumption; the prevalence of cataract rose with further
      increases in consumption, suggesting a U-shaped curve. For nuclear cataract,
      white in particular, there is a significant trend with amount consumed. Smoking
      was not found to be a risk factor.

PMID- 8878188
TI  - Increased cytokine gene expression in rat retina following transient ischemia.
AB  - Tumor necrosis factor (TNF) gene expression in rat retina following transient
      ischemia was studied by semiquantitative reverse transcription-polymerase chain
      reaction (RT-PCR). Gene expression for other cytokines was also studied by RT
      PCR. Although very little expression for TNF gene was detected in normal retina,
      it was markedly increased 0.5-48 h after reperfusion, with peak expression at 12
      h (20-fold of control). Gene expression for interleukin-6, interferon-gamma, and
      transforming growth factor-beta 1 was also increased. The results provide
      evidence that retinal ischemia can up-regulate cytokine gene expression in the
      retina.

PMID- 8878189
TI  - Early changes in the choroidal vasculature of rats occurring with experimentally
      induced hypertension.
AB  - We investigated the early changes in the choroidal vasculature in rats following
      surgically induced renovascular hypertension. Renovascular hypertension was
      induced in a group of 12 male Wistar rats using a modified Goldblatt procedure.
      The rats were divided into four groups, each being sacrificed at weekly
      intervals, the first group being sacrificed 1 week following the procedure.
      Vascular casts were prepared of the choroidal circulation using acyl resin
      (mercox). These were then studied using the scanning electron microscope. No
      abnormality of the choroidal circulation was noted for the first 2 weeks. At 3
      weeks, when a rise in the average mean arterial pressure was noted, nodular
      lesions were seen in the choroidal arteries and choriocapillaris. These lesions
      were present in far greater numbers by 4 weeks. It seems likely that the nodular
      lesions described are microaneurysms and may contribute to the pathogenesis of
      the clinically described Elschnig spot.

PMID- 8878190
TI  - Effects of a nitric oxide synthase inhibitor on prostaglandin-induced aqueous
      flare elevation in pigmented rabbits.
AB  - To evaluate the possible role of nitric oxide in the pathogenesis of exogenous
      prostaglandin (PG) induced aqueous flare elevation, we examined the effect of NG
      nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue acting as a
      specific inhibitor of nitric oxide synthase, on the elevation of aqueous flare in
      pigmented rabbits. L-NAME was injected into the ear vein of the animals. PGE1,
      PGE2, and PGF2 alpha were administered topically to the cornea using a glass
      cylinder. Aqueous flare was measured using a laser flare cell meter. PGE1, PGE2,
      and PGF2 alpha increased the aqueous flare dose dependently (5-100
      micrograms/ml). L-NAME inhibited PGE1-, PGE2-, or PGF2 alpha-induced aqueous
      flare elevation. L-NAME, injected 30-90 min before PG application, inhibited the
      aqueous flare elevation maximally. We believe that nitric oxide may be involved
      in the pathogenesis of PG-induced aqueous flare elevation in rabbits.

PMID- 8878191
TI  - Anterior chamber maintenance during drainage of a suprachoroidal hemorrhage in
      two phakic eyes.
AB  - BACKGROUND AND OBJECTIVES: The authors describe a technique for hemorrhage
      drainage following glaucoma surgery that uses an anterior chamber maintainer to
      minimize risk to the anterior lens capsule. PATIENTS AND METHODS: Two patients
      had suprachoroidal hemorrhages following filtration surgery. Because their eyes
      were phakic, an anterior chamber maintainer, as opposed to a 23-gauge butterfly
      needle, was used for aqueous replacement during hemorrhage drainage. RESULTS: The
      maintainer provided a stable anterior chamber environment during both drainage
      procedures. No damage to anterior chamber structures occurred, and the
      postoperative course was unremarkable in both patients. CONCLUSIONS: The use of a
      sharp-tipped infusion cannula may be contraindicated for the phakic patient who
      has a suprachoroidal hemorrhage. The anterior chamber maintainer is a useful
      alternative instrument in such cases.

PMID- 8878192
TI  - Detection of disturbed autoregulation of the peripapillary choroid in primary
      open angle glaucoma.
AB  - BACKGROUND AND OBJECTIVE: This study is concerned with perfusion-pressure
      videoangiographic investigations, performed by combining oculo-oscillo
      dynamography and videoangiography. Perfusion-pressure videoangiography permits an
      evaluation of local vascular resistance in the choroid relative to ciliary
      perfusion pressure. PATIENTS AND METHODS: Twelve healthy subjects, 21 patients
      with primary open angle glaucoma (POAG), and 27 patients with ocular hypertension
      were examined. RESULTS: Perfusion-pressure videoangiograms revealed that the
      peripapillary choroid (nasal main ciliary artery) filled at distinctly lower
      perfusion pressures than the paramacular region (temporal main ciliary artery) in
      all 12 healthy subjects, with a perfusion pressure difference of 12.5 +/- 4.9 mm
      Hg. In the 21 patients with POAG, the perfusion pressure difference between the
      beginning of peripapillary and paramacular perfusion was as small as 3.7 +/- 4.5
      mm Hg. In the 27 patients with ocular hypertension, the perfusion pressure
      difference between the two circulatory regions was almost as high as in the
      healthy subjects. CONCLUSIONS: These examinations showed that (1) there exists
      efficient autoregulation in the peripapillary choroids of healthy subjects, (2)
      autoregulation is diminished or even absent in POAG, and (3) autoregulation is
      normal, increased, or slightly reduced in ocular hypertension.

PMID- 8878193
TI  - Comparison of Fastpak with full-threshold 24-2 glaucoma field tests.
AB  - BACKGROUND AND OBJECTIVES: The authors noted an underestimation of the mean
      deviation for field testing using the Fastpak (Humphrey Instruments, San Leandro,
      CA) strategy, and set out to define the extent of this difference. PATIENTS AND
      METHODS: Sixty-seven eyes of 35 glaucomatous patients were examined. Patients
      received full-threshold 24-2 tests before and after the Fastpak strategy was
      used, each test on a different day. For some patients, another full-threshold
      test was performed using a different birth date in order to obtain a result
      uninfluenced by prior data. RESULTS: The mean deviation (MD) was significantly
      underestimated by Fastpak compared with the full-threshold tests. The time taken
      for Fastpak was almost identical to that taken for full-threshold tests. Short
      term fluctuation (SF) appeared to have very little reliability statistically,
      and, consistent with this, there was a greater concordance among pattern standard
      deviation (PSD) data than among corrected pattern standard deviation (CPSD) data.
      CONCLUSION: Fastpak was an effective method for charting the visual field, but
      did so with greater variation than full-threshold tests. It significantly
      underestimated the MD, and this was not a fatigue effect. Fastpak was no faster
      than full-threshold testing in advanced glaucoma. CPSD was a less consistent
      reading than PSD in these glaucomatous patients.

PMID- 8878194
TI  - Sustained-release subconjunctival 5-fluorouracil.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this research was to obtain preliminary
      safety and efficacy data on a novel sustained-release 5-fluorouracil (5-FU)
      implant in high-risk glaucoma surgical patients. PATIENTS AND METHODS: The
      implants were placed subconjunctivally in four patients undergoing high-risk
      trabeculectomy. The patients have been observed for approximately 2.5 years.
      RESULTS: In three of the four patients intraocular pressure was controlled at
      less than 21 mm Hg, with stabilization of the visual field. One patient had early
      failure. No untoward events were linked to the placement of the implant.
      CONCLUSION: Sustained-release systems for subconjunctival 5-FU may be useful in
      filter maintenance.

PMID- 8878195
TI  - Excimer laser phototherapeutic keratectomy for recurrent erosions: a clinical
      study.
AB  - BACKGROUND AND OBJECTIVE: Recurrent corneal erosion is a common corneal disease.
      It may be difficult to treat, with a number of patients suffering persistent
      symptoms despite having had conventional therapy. The aim of this study was to
      evaluate the usefulness of the excimer laser for the treatment of recurrent
      corneal erosions. PATIENTS AND METHODS: The authors studied 31 eyes of 24
      patients who underwent excimer laser phototherapeutic keratectomy (PTK) for
      recurrent corneal erosion. Three eyes were treated during an acute episode of
      recurrent erosion. The remaining eyes were treated during a symptom-free
      interval. The affected area of epithelium was removed and a 25 pulse ablation was
      performed to Bowman's membrane. RESULTS: In 30 eyes there was a marked
      improvement in symptoms postoperatively, with no recurrences. However, 1 eye had
      one recurrent episode 2 weeks after PTK. Postoperatively, refraction and corneal
      topography were unaltered in all cases. CONCLUSIONS: Excimer laser PTK appears to
      be a safe and promising procedure for cases of recurrent corneal erosion
      refractory to medical treatment.

PMID- 8878196
TI  - Sub-Tenon's versus retrobulbar anesthesia for cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: A prospective, randomized, double-blind study was
      conducted to compare sub-Tenon's anesthesia with retrobulbar anesthesia. PATIENTS
      AND METHODS: One hundred six patients undergoing cataract extraction received
      either sub-Tenon's anesthesia (55 patients) or retrobulbar anesthesia (51
      patients). The number of injections required, time until adequate akinesia was
      achieved, degree of pain experienced, and complications of the anesthetic
      injection were compared. The depth of the akinesia after sub-Tenon's injection
      was graded. RESULTS: There was no significant difference between the two study
      groups with respect to time of onset of adequate akinesia, the need for a second
      top-up injection, and the effectiveness of the akinesia. The sub-Tenon's
      injection group reported less pain during the anesthetic injection, as well as
      during the postoperative injection of subconjunctival gentamicin. CONCLUSION: Sub
      Tenon's anesthesia is a safe technique that is comparable to retrobulbar
      anesthesia.

PMID- 8878197
TI  - Use of perfluorocarbon liquid in the repair of retinoschisis retinal detachments.
AB  - BACKGROUND AND OBJECTIVES: To determine the effectiveness of perfluorocarbon
      liquid in the repair of retinoschisis-associated retinal detachments. PATIENTS
      AND METHODS: Four patients with either degenerative or juvenile X-linked
      retinoschisis had rhegmatogenous retinal detachments that were repaired with the
      use of perfluorocarbon liquid during vitrectomy. The patients' ages ranged from
      17 to 78 years and the postoperative follow-up was at least 6 months. RESULTS:
      All of the patients had complete anatomic repair of the retinoschisis-associated
      retinal detachments. The postoperative visual acuity was 20/200 or better in all
      of the patients and 20/40 or better in half of the patients. CONCLUSIONS: The use
      of perfluorocarbon liquid is an effective adjunct in the management of
      rhegmatogenous retinal detachments associated with degenerative and juvenile X
      linked retinoschisis.

PMID- 8878198
TI  - Ocular conditions associated with posterior vitreous detachment in young
      patients.
AB  - BACKGROUND AND OBJECTIVE: To investigate the ocular conditions associated with
      posterior vitreous detachment (PVD) in young patients. PATIENTS AND METHODS: The
      vitreous conditions of 861 patients younger than 30 years were studied
      retrospectively and examined biomicroscopically. RESULTS: In the first and second
      decades of life, retinitis pigmentosa, nondiabetic retinal vascular disorders,
      and a history of ocular contusion were most commonly associated with PVD. In the
      third decade of life, proliferative diabetic retinopathy was overwhelmingly the
      condition most commonly associated with PVD. CONCLUSION: This study delineated
      the ocular pathologic conditions associated with PVD in young patients. These
      findings may be useful in the management of PVD in patients younger than 30
      years.

PMID- 8878199
TI  - Effect of scleral buckling on unsutured cataract wound strength.
AB  - BACKGROUND AND OBJECTIVE: Modern cataract surgery has evolved to include small,
      unsutured wounds with rapid visual rehabilitation and fewer complications.
      Properly constructed, these unsutured wounds can withstand increased intraocular
      pressures without leakage, rupture, or incarceration of intraocular contents.
      However, scleral buckling surgery may alter the architecture of these wounds and
      thus their strength. The authors wanted to study the effect of scleral buckling
      on the integrity of these unsutured cataract wounds. MATERIALS AND METHODS:
      Eighteen fresh human globes underwent creation of scleral and limbal corneal
      incisions so as to create self-sealing wounds. Scleral buckles were then placed.
      Intraocular pressures were elevated to 400 mm Hg before and after placement of
      the scleral buckles and evidence for wound leakage was sought. RESULTS: Two
      globes with clear corneal incisions and no scleral buckles leaked slightly at 300
      mm Hg, but no globe with a scleral buckle, regardless of incision type or
      silicone element style, leaked at pressures to 400 mm Hg. CONCLUSION: Sutureless
      cataract incisions, if properly constructed, provide a strong, pressure-resistant
      wound. Scleral buckling does not appear to affect the strength of these wounds.

PMID- 8878200
TI  - Ultrastructural features of filtration blebs with different clinical appearances.
AB  - The authors studied two functioning filtration blebs to evaluate a possible
      transconjunctival route of aqueous humor flow and describe potential differences
      between thin cystic and thick opaque functioning filtration blebs. The specimens
      were prepared for light and electron microscopy immediately after surgical
      excision because of filtration bleb discomfort. Both blebs had normal collagen in
      the substantia propria. The collagen, however, was widely spaced and
      subepithelial connective tissue loosely arranged. Clear spaces were seen in the
      superficial substantia propria. Epithelial cells were focally acantholytic,
      separated by clear spaces. Consequently, clinically distinct blebs demonstrated
      similar histologic and ultrastructural features. The epithelial intercellular
      spaces observed in this study provide anatomic evidence that aqueous could move
      transconjunctivally as a mechanism for filtration bleb function.

PMID- 8878201
TI  - Recurrent choroidal detachment following combined trabeculectomy and cataract
      extraction.
AB  - Two patients with glaucoma who underwent uneventful trabeculectomy and
      extracapsular cataract extraction with posterior chamber intraocular lens
      implantation, experienced late and recurrent choroidal detachment. Both patients
      received aqueous suppressant therapy before and after surgery. Hypotony and
      choroidal detachment occurred 7 months and 15 months after the combined surgery.
      There was no shallowing of the anterior chamber or leakage from the filtering
      blebs, and there were no signs of inflammation. The choroidal detachment
      completely resolved in the two patients 4 days and 4 weeks following
      discontinuation of the aqueous suppressant therapy.

PMID- 8878202
TI  - Infected orbital cyst following exenteration.
AB  - An orbital cyst is a rare complication of orbital trauma and exenteration.
      Infections of such cysts have not been described, and are potentially dangerous
      unless treated immediately. The authors describe a case of delayed treatment of
      such an infected cyst, which resolved following surgical drainage. The
      potentially hazardous outcome makes knowledge of such cases important.

PMID- 8878203
TI  - Resiting Molteno implant tubes.
AB  - The authors describe a surgical technique for resiting Molteno implant tubes. The
      indications for this intervention are a blockage of the tube that cannot be
      resolved by other means; erosion of the scleral flap and conjunctiva by the tube;
      and pediatric cases in which enlargement of the eye causes retraction of the tube
      from the anterior chamber.

PMID- 8878204
TI  - The extended Jones tube.
AB  - Conjunctivo-dacryocystorhinostomy with a Jones glass tube serving as a conduit
      for tear flow is used in patients with epiphora resulting from obstructed
      canaliculi. The glass tube runs from the medial canthus into the nose. The author
      describes the use of an extended Jones tube in a patient without a nose.

PMID- 8878205
TI  - The usefulness of dapiprazole, an alpha-adrenergic blocking agent, in pigmentary
      glaucoma.
AB  - The aim of this study was to increase understanding of the usefulness of an alpha
      adrenergic blocking agent, dapiprazole 0.5% eyedrops, as an adjunct in
      antiglaucomatous therapy for 20 patients with pigmentary glaucoma receiving
      timolol 0.5% and pilocarpine 1%. After 12 months of dapiprazole treatment, the
      difference from the pretreatment mean intraocular pressure (IOP) value was
      statistically significant (P = .005). After 12 and 36 months of treatment, an
      hour-to-hour comparison of diurnal IOP curve values showed a statistically
      significant difference in all cases (P < .001). Although further investigations
      may be necessary to reach a definite conclusion, dapiprazole appeared to have a
      beneficial, stable in time effect in these patients.

PMID- 8878206
TI  - The concept of chronic open-angle glaucoma: a personal view.

PMID- 8878207
TI  - Glaucoma, capillaries and pericytes. 1. Blood flow regulation.
AB  - Blood flow autoregulation may be deficient in patients with glaucoma, making the
      optic nerve circulation susceptible to the challenge of intraocular pressure
      (IOP). Adequacy or inadequacy of autoregulation may be a factor that decides
      whether a patient with elevated IOP develops glaucomatous optic nerve damage.
      Hypothetically, capillaries may assist arteries and veins in the regulation of
      blood flow. Our attention has become focused on the pericytes, particularly
      abundant in the optic nerve and retina, which are a contractile component of
      capillaries and may therefore be the cells responsible for the capillary's role
      in autoregulation.

PMID- 8878208
TI  - Glaucoma, capillaries and pericytes. 2. Identification and characterization of
      retinal pericytes in culture.
AB  - As cell cultures of pericytes derived from bovine retina are in regular use by a
      number of investigators, we decided to confirm the identity of these cells, to
      show them different from other cells that might contaminate cultures derived from
      retinal tissue, to characterize the properties they share with pericytes in situ
      and to establish a practical and effective means for confirmation of the cell
      type of each batch of cultured cells used in scientific studies. Cultured
      pericytes differed in immunocytochemical reactions and phagocytic properties from
      vascular smooth muscle, vascular endothelial cells, astroglia, conjunctival
      fibroblasts or retinal pigment epithelium. Like vascular smooth muscle, pericytes
      in situ and those in culture have the contractile proteins actin and myosin,
      which implies a potential role in blood flow control. In routine studies of
      cultured pericytes, they can be identified by their unique reaction in situ and
      in vitro with the antiganglioside monoclonal antibody 3G5. The presence of any
      contaminating endothelial cells can be recognized by their ability to take up
      acetylated low-density lipoprotein.

PMID- 8878209
TI  - Glaucoma, capillaries and pericytes. 3. Peptide hormone binding and influence on
      pericytes.
AB  - To test the potential for vasoactive neuropeptide receptors to affect capillary
      resistance, we have begun to study the plausibility that pericytes might be
      equipped to respond to a representative peptide vasoconstrictor and a
      representative peptide vasodilator. Pericytes cultured from the bovine retinal
      vasculature specifically bind the angiotensin II (Ang II) antagonist saralasin (1
      nM125I-saralasin bound at 2.2 +/- 0.41 fmol/mg protein) and 125I-vasoactive
      intestinal peptide (VIP; Kd of 0.5 nM with a population of 30 fmol/mg protein).
      Incubation with 100 microM Ang II induced minimal cAMP synthesis, while VIP (1
      microM, 10 microM) did not induce any change in cAMP concentration. Ang II (10
      microM and 100 microM) caused contraction of pericytes cultured on an elastic
      silicone surface. Circulating or locally produced vasoactive neuropeptides might
      affect pericyte contractile tone via several intracellular pathways, moderated by
      indirect effects of these peptides through endothelial stimulation, with the net
      effect on local blood flow resulting from the effects on arteries and veins as
      well as capillaries.

PMID- 8878210
TI  - Glaucoma, capillaries and pericytes. 4. Beta-adrenergic activation of cultured
      retinal pericytes.
AB  - To characterize the relaxation of pericytes induced by beta-adrenergic
      stimulation, changes in the contractile tone of pericytes were quantified as a
      change in the wrinkling of an elastic silicone surface on which they were
      cultured. Isoproterenol produced relaxation of pericytes in a dose-dependent
      manner over a range of 5 nM to 1 microM. Low concentrations of the nonselective
      beta-blockers propanolol and timolol blocked the relaxation produced by
      isoproterenol. The specific beta 2-adrenergic component of isoproterenol-induced
      relaxation was shown by blockage with bromoacetyl alprenolol menthane. In
      contrast, atenolol and betaxolol, as relatively selective beta 1-adrenergic
      blockers, had no effect on the isoproterenol-induced relaxation.

PMID- 8878211
TI  - Glaucoma, capillaries and pericytes. 5. Preliminary evidence that carbon dioxide
      relaxes pericyte contractile tone.
AB  - We undertook this study to determine if pericytes respond to carbon dioxide in a
      manner such that they could help control capillary blood flow and that their
      physiologic responses to pCO2 might be worthy of detailed study. Pericytes were
      isolated from bovine retinas and grown in cell culture. Changes in the
      contractile tone of the pericytes upon changing the ambient pCO2 were observed by
      noting changes in the wrinkling of an elastic silicone surface on which they were
      grown. An increase in pCO2 caused acidosis of the medium and relaxation of the
      pericytes in a reversible, concentration-dependent manner. These findings suggest
      that the regulation of blood flow to meet local metabolic needs does not reside
      entirely in the arterioles and precapillary sphincters, but at least in part in
      the capillary bed through the contractile properties of pericytes. The local pCO2
      is one of several potential indicators of whether or not local blood flow is
      adequate for local tissue needs. The response to local conditions may modulate or
      be modulated by the effect of neurotransmitters and hormones on the local rate of
      blood flow.

PMID- 8878212
TI  - Blood supply of the optic nerve head.
AB  - The subject of the blood supply of the optic nerve head (ONH) is reviewed
      briefly. The circulation of the posterior ciliary artery is the main source of
      blood supply to the ONH, except for the surface nerve fiber layer which is
      supplied by the retinal circulation. The blood supply in the ONH is sectoral in
      nature, which is the reason why there is the sectoral involvement of the ONH in
      its ischemic disorders. It is essential to understand that the pattern of blood
      supply in the ONH shows marked interindividual variation, and so consequently
      does the pattern of visual loss in its ischemic disorders. The venous drainage
      from the ONH is by the central retinal vein. Reasons for various controversies on
      the subject are discussed.

PMID- 8878213
TI  - Presence of a contractile cell network in the human choroid.
AB  - Immunohistochemical staining of choroidal whole mounts as well as serial
      tangential sections and electron-microscopic investigation of 21 human donor eyes
      revealed a network of nonvascular alpha-smooth-muscle-actin-positive cells
      (NVSMC) in the entire choroid most densely arranged in the posterior part of the
      suprachoroid of the submacular region. Ultrastructurally these cells present the
      typical structure of myofibroblasts. Double labeling with desmin and smooth
      muscle myosin showed a positive reaction only in few of these cells. Posteriorly
      the NVSMC net reaches the optic nerve, anteriorly it ends in the region of the
      vortex veins but does not continue into the ciliary muscle. In places, intimate
      contact between the contractile cells and the elastic fiber network of the
      choroidal stroma and the perivascular sheaths is seen. The elastic net of the
      choroid is firmly connected with the posterior elastic tendons of the ciliary
      muscle. In the course of accommodation, the ciliary muscle pulls this net
      foreward presumably influencing position and diameter of the choroidal vessels.
      We assume that the network of NVSMC of the choroid counteracts the ciliary body
      movements during accommodation, thus guaranteeing the three-dimensional
      architecture of the choroid and the position of the retina, particularly in the
      macular region.

PMID- 8878214
TI  - Aceclidine effects on outflow facility after ciliary muscle disinsertion.
AB  - Aceclidine increases outflow facility with little accommodative effect. To
      determine whether this dissociation resides in the ciliary muscle (CM) or
      trabecular meshwork (TM), we measured aceclidine effects on perfusion outflow
      facility in both eyes of 8 rhesus monkeys after unilateral disinsertion of the CM
      from the TM. Facility in the control eyes increased by approximately 250%
      following intravenous pilocarpine and by an additional approximately 250%
      following intracameral pilocarpine, relative to baseline and uncorrected for
      washout. In CM-disinserted eyes, the facility response to intravenous and
      intracameral pilocarpine averaged approximately 25% of that in contralateral
      controls. Cytochalasin B, which acts directly on the TM to increase facility but
      is not additive to maximal pilocarpine doses in normal eyes, had no additional
      effect beyond that of pilocarpine in control eyes but induced an additional 100%
      facility increase relative to baseline in CM-disinserted eyes. The accommodative
      response to carbachol in CM-disinserted eyes was approximately 80% of that in
      contralateral controls, consistent with retention of CM contractility and the
      gonioscopic appearance of shallow CM disinsertion. Intracameral aceclidine HCl
      doses of 5 and 50 micrograms increased outflow facility by approximately 80 and
      250%, respectively, in control eyes, and by approximately 0 and 80% in CM
      disinserted eyes. Either the low aceclidine dose affected facility via the CM,
      while the high dose exerted an additional effect on the TM, or aceclidine acted
      only via the CM, with the low dose being ineffective and the high dose modestly
      effective in CM-disinserted eyes because only a few CM-TM attachments remained.

PMID- 8878215
TI  - Do beta-adrenoceptors and serotonin 5-HT1A receptors have similar functions in
      the control of intraocular pressure in the rabbit?
AB  - Serotonin 5-HT1A-type and beta-adrenergic receptors have similar molecular
      characteristics, which explains why certain substances like propranolol have
      affinities for both receptor types. Activation of 5-HT1A receptors leads to a
      decrease in intracellular cAMP levels whereas the opposite occurs for beta
      adrenergic receptors. Both 5-HT1A and beta-adrenergic receptors exist in the
      rabbit ciliary processes. Topical application of the 5-HT1A agonist, 8
      hydroxydipropylaminotetralin (8-OH-DPAT) reduces intraocular pressure (IOP). beta
      Antagonists are also known to reduce IOP. It is postulated that substances which
      have an affinity for 5-HT1A and/or beta-adrenergic receptors and lead to a
      reduction in intracellular cAMP levels in the ciliary processes diminish IOP.

PMID- 8878216
TI  - Misdiagnosis of Lyme disease: when not to order serologic tests.

PMID- 8878217
TI  - Comparison study of the immunogenicity and safety of 5- and 10-microgram dosages
      of a recombinant hepatitis B vaccine in healthy infants.
AB  - BACKGROUND: It has been suggested that lower dosages of hepatitis B vaccine may
      be adequate for vaccinating infants and would be less costly. OBJECTIVES: To
      compare the immunogenicity and safety of 5 and 10 micrograms of Engerix-B
      recombinant hepatitis B vaccine given to healthy infants. METHODS: A prospective
      randomized comparison of 5- and 10-micrograms doses of Engerix-B recombinant
      hepatitis B vaccine given to infants at 2, 4 and 6 months of age. Seroconversion
      (antihepatitis B surface antigen (anti-HBs) > or = 1 mIU/ ml) and seroprotection
      (anti-HBs > or = 10 mIU/ml) rates as well as geometric mean antibody titers were
      compared at 4, 6 and 8 months. RESULTS: A total of 190 healthy infants were
      screened and received the first dose of vaccine. Of these infants 153 were
      eligible to continue in the study. Both dosages proved to be highly immunogenic,
      producing high seroconversion and seroprotection rates and geometric mean anti
      HBs concentrations after 3 doses. Although 10 micrograms induced significantly
      greater geometric mean concentrations (1641 mIU/ml compared 880 mIU/ml at 8
      months of age), the seroprotection rates were identical (98.5%). CONCLUSIONS:
      Both dosages were well-tolerated and no serious adverse experiences were
      reported. However, the 5 micrograms of Engerix-B administered at 2, 4 and 6
      months of age did not induce as great an anti-Hbs concentration as did 10
      micrograms. Long term studies are required to determine whether using the lower
      dosage would sacrifice long term efficacy.

PMID- 8878218
TI  - Comparison study of the immunogenicity and safety of 5- and 10-microgram dosages
      of a recombinant hepatitis B vaccine in healthy children.
AB  - OBJECTIVE: To compare the immunogenicity and safety of 5 micrograms with 10
      micrograms of Engerix-B recombinant hepatitis B vaccine when given to healthy
      children, 2 to 6 years of age. METHODS: Randomized multicenter study of
      serongative children 2 to 6 years of age who received Engerix-B hepatitis B
      vaccine either 5 micrograms/0.25 ml or 10 micrograms/0.5 ml (the current Food and
      Drug Administration-approved dosage of Engerix-B in children) at 0, 1 and 6
      months. Serum was obtained at 1, 3, 6 and 8 months after the first vaccine dose
      was given for antibody measurement. RESULTS: A total of 223 subjects were
      screened and received the first dose of vaccine. Of these subjects 193 continued
      in the study. Both dosages proved to be highly immunogenic, producing high
      seroconversion and seroprotection rates and geometric mean antibody to hepatitis
      B surface antigen concentrations after 3 doses. The geometric mean concentrations
      of seroconverters at Months 6 and 8 were significantly greater for the 10
      micrograms group compared with the 5-micrograms group. Both dosages were well
      tolerated and no serious adverse events were reported. CONCLUSIONS: There was a
      significant reduction in geometric mean concentrations on lowering the dosage of
      Engerix-B from 10 to 5 micrograms in children 2 to 6 years of age. Although a
      high seroprotection rate was elicited by the 5-micrograms dose, the lower
      antibody concentrations achieved may make this lower dosage less desirable in the
      long term. Further studies are required to examine the need for booster doses of
      vaccine with both dosing schedules.

PMID- 8878219
TI  - Recombinant hepatitis B vaccination of neonates and infants: emerging safety data
      from the Vaccine Adverse Event Reporting System.
AB  - OBJECTIVES: To evaluate the postmarketing safety of recombinant hepatitis B (HB)
      vaccine given to neonates and infants in the US. METHODS: US reports associated
      with HB vaccination and received between January 1, 1991, and May 31, 1995, by
      the national Vaccine Adverse Events Reporting System (VAERS) were reviewed as a
      case series. RESULTS: During 1991 through 1994, 12,520 (32%) VAERS reports were
      received for events temporally associated with administration of HB vaccine, of
      which 14% were received for neonates and infants. More reports described serious
      outcomes for neonates (< 0.1 year old) than for other age groups (40% vs. 6 to
      15%). HB alone was administered to 58 (97%) neonates; review of these reports did
      not reveal unexpected serious events. Among infants (0.1 to 0.9 years old) 192
      (9%) received HB vaccine alone and 1469 (66%) received HB in combination with
      diphtheria-tetanus-pertussis (DTP) vaccine. Similar serious adverse events
      reported in neonates and infants included fever, agitation and apnea. Events
      reported for infants receiving HB/DTP and DTP alone were similar and differed
      from reports filed for infants receiving HB vaccine alone, suggesting that these
      events may be associated with use of DTP vaccine. CONCLUSIONS: This review shows
      no unexpected adverse events in neonates and infants given HB vaccine despite use
      of at least 12 million doses of vaccine given in these age groups. Although VAERS
      lacks the ability to distinguish coincidental events from true vaccine reactions,
      this database represents the largest case series of events temporally associated
      with HB vaccination of neonates and infants.

PMID- 8878220
TI  - Vitamin A therapy for children with respiratory syncytial virus infection: a
      multicenter trial in the United States.
AB  - BACKGROUND: High dose vitamin A therapy is effective in reducing morbidity and
      mortality associated with measles infection. Children with acute respiratory
      syncytial virus (RSV) infection have low serum vitamin A concentrations. METHODS:
      We performed a multicenter, randomized, placebo-controlled trial of high dose
      vitamin A therapy among 239 children 1 month to 6 years of age to determine
      whether high dose vitamin A therapy would reduce morbidity associated with RSV
      infection. RESULTS: There were no differences between the vitamin A and placebo
      recipients for most clinical outcomes; however, vitamin A recipients had-longer
      hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after
      enrollment. This effect was significant for children who were older than 1 year
      (who also had received the highest doses of vitamin A), particularly among those
      at low risk for complications of RSV infection and those enrolled during the
      second study season. Serum retinol levels at enrollment were inversely correlated
      with severity of illness. CONCLUSIONS: We found no evidence of a beneficial
      effect of vitamin A for the treatment of RSV infection in children in the United
      States. There may be groups of children for which vitamin A has an adverse
      effect, resulting in longer hospital stays.

PMID- 8878221
TI  - Treatment of respiratory syncytial virus infection with vitamin A: a randomized,
      placebo-controlled trial in Santiago, Chile.
AB  - BACKGROUND: Treatment with high dose vitamin A reduces complications and duration
      of hospitalization for children with measles. In respiratory syncytial virus
      (RSV) infection, as with measles, low serum vitamin A concentrations correlate
      with increased severity of illness. METHODS: To determine whether high dose
      vitamin A treatment is also effective for treating RSV disease, we conducted a
      randomized, double blind, placebo-controlled trial among 180 RSV-infected
      children between 1 month and 6 years of age at three hospitals in Santiago,
      Chile. Children with nasal washes positive for RSV antigen were given oral
      vitamin A (50,000 to 200,000 IU of retinyl palmitate, doses according to age; n =
      89) or placebo (n = 91) within 2 days of admission. RESULTS: There was no
      significant benefit from vitamin A treatment for the overall group in duration of
      hospitalization, need for supplemental oxygen or time to resolve hypoxemia. For
      the subgroup of children with significant hypoxemia on admission (room air oxygen
      saturation level < or = 90%), those given vitamin A had more rapid resolution of
      tachypnea (P = 0.01) and a shorter duration of hospitalization (5.5 vs. 9.3 days,
      P = 0.09). No toxicities were seen, including excess vomiting or bulging
      fontanel. CONCLUSIONS: If vitamin A has a beneficial effect on the course of RSV
      disease, it may be seen only in more severely ill children.

PMID- 8878222
TI  - Salivary testing for human immunodeficiency virus type 1 infection in children
      born to infected mothers in Sao Paulo, Brazil. The Sao Paulo Collaborative Study
      for Vertical Transmission of HIV-1.
AB  - OBJECTIVE: To validate a method for salivary testing for HIV infection in
      children older than 12 months. METHODS: Oral fluid samples were collected via
      sponge foam swabs from children born to HIV-positive mothers and were tested for
      antibodies to HIV-1 and HIV-2 with an IgG antibody capture enzyme-linked
      immunosorbent assay and a modified Western blot for confirmation. In each child
      serum antibody status was the standard used to validate the salivary antibody
      test. RESULTS: We obtained 331 oral fluid samples from children born to HIV
      positive mothers. The specificity and sensitivity of salivary testing compared
      with results on sera were both 100% (297 of 297 (95% confidence interval 98.8 to
      100%) and 34 of 34 (95% confidence interval 89.7 to 100%), respectively).
      Compliance in the study population increased from 91% to 97% when mothers were
      offered the opportunity to provide oral fluid from their children instead of
      blood specimens. CONCLUSION: Salivary testing provides an accurate and acceptable
      noninvasive method for assessing the HIV infection status of children born to
      infected mothers by using IgG antibody capture enzyme-linked immunosorbent assay
      alone with a strategy of duplicate retesting of reactive specimens.

PMID- 8878223
TI  - Evaluation of the efficacy, safety and toleration of azithromycin vs. penicillin
      V in the treatment of acute streptococcal pharyngitis in children: results of a
      multicenter, open comparative study. The Swiss Tonsillopharyngitis Study Group.
AB  - BACKGROUND: For many years alternatives to penicillin have been studied for the
      management of pediatric group A beta-hemolytic Streptococcus (GABHS) pharyngitis.
      As a result of its pharmacokinetic profile azithromycin is unique among these
      alternative antimicrobials in allowing once daily dosing and shorter duration of
      treatment. However, the optimum dose (e.g. 10 or 12 mg/kg/day) and duration (e.g.
      3 or 5 days) of azithromycin therapy have not been defined yet. METHODS: An open,
      comparative multicenter study was conducted in 343 children with clinical
      symptoms of GABHS pharyngitis and a positive culture to evaluate the efficacy and
      safety of azithromycin (10 mg/kg) once daily for 3 days compared with penicillin
      V three times daily for 10 days. RESULTS: Among the evaluable patients
      bacteriologic eradication documented at follow-up visits was inferior with
      azithromycin when compared with penicillin V therapy: at Days 9 to 20 (mean, 12
      days), negative cultures in 65% (99 of 152 patients) vs. 82% (128 of 126
      patients) (P < 0.001); and at Days 17 to 57 (mean, 25 days), in 55% vs. 80% (P <
      0.001). Overall clinical success (cure or improvement) was achieved in 93% (149
      of 160 patients) of azithromycin-treated and in 89% (143 of 160 patients) of
      penicillin-treated patients (P > 0.50). There was no correlation between
      bacteriologic response and clinical outcome, as assessed shortly after completion
      of therapy or during 6-month follow-up. Both treatments were well-tolerated.
      CONCLUSIONS: In the present study on GABHS pharyngitis in children, a once daily
      (10-mg/kg), 3-day oral regimen of azithromycin was as clinically effective and as
      safe as traditional penicillin but appeared inferior in eliminating GABHS from
      the throat.

PMID- 8878224
TI  - Cryptococcosis in human immunodeficiency virus-infected children.
AB  - BACKGROUND: Cryptococcosis is a common opportunistic infection in adults with
      AIDS. Few cases of cryptococcosis complicating pediatric AIDS have been reported.
      To our knowledge there are no studies that describe the epidemiology, clinical
      manifestations and outcome of cryptococcosis in a large population of HIV
      infected children. METHODS: We identified the cases of cryptococcosis through a
      retrospective review of the hospital records of the 473 HIV-infected children
      prospectively monitored in the Pediatric Branch of the National Cancer Institute
      during the 8 years from 1987 to 1995. RESULTS: Four (0.85%) patients developed
      cryptococcosis during the study period. All patients had profound depression of
      the absolute CD4 counts, a history of previous opportunistic infections, and
      onset of cryptococcosis in the second decade of life. Cryptococcosis developed as
      a disseminated infection or a localized process of the lungs. Intermittent fever
      was the most common presenting manifestation. Serum cryptococcal antigen was
      positive in all patients and gradually declined after the institution of the
      antifungal therapy. All patients were treated with amphotericin B with or without
      flucytosine as initial therapy. Suppressive therapy consisted of fluconazole with
      or without flucytosine. There were no deaths due to Cryptococcus neoformans.
      CONCLUSIONS: Cryptococcosis is an infrequent yet treatable opportunistic
      infection of advanced pediatric AIDS that may present with subtle manifestations
      and warrants careful consideration in the evaluation of febrile HIV-infected
      children.

PMID- 8878225
TI  - Neonatal enterococcal bacteremia: an increasingly frequent event with potentially
      untreatable pathogens.
AB  - BACKGROUND: Enterococci can cause serious infections in the newborn. The
      increased number of these infections since the late 1970s and the increased
      isolation of organisms resistant to many commonly used antimicrobials prompted
      review of our experience with enterococcal bacteremia in the neonatal intensive
      care unit. This review was aimed at defining the character of illness of newborns
      who had these infections during a 20-year period. METHODS: This was a
      retrospective review of the medical records of newborns with enterococci isolated
      from blood. RESULTS: Between January, 1974, and December, 1993, 138 episodes of
      enterococcal bacteremia occurred in newborns hospitalized in the neonatal
      intensive care unit. Thirty-four episodes occurred during the first decade and
      104 episodes during the second decade. One hundred of the 138 episodes were
      reviewed. In 64% of these episodes other microorganisms were also isolated from
      blood. Comparison of clinical characteristics associated with these episodes in
      the first and second decade demonstrated that episodes occurring in the more
      recent decade occurred in older infants (mean age of onset, 44.7 vs. 16.1 days;
      episodes occurring after 14 days, 73% vs. 41%). Common characteristics associated
      with enterococcal bacteremia included the presence of a central vascular catheter
      (77%), necrotizing enterocolitis (33%) and abdominal distension (21%). Vancomycin
      resistant enterococci caused bacteremia in 6 infants and caused illnesses
      indistinguishable from those caused by susceptible organisms. CONCLUSIONS: In the
      more recent decade there were three times the number of episodes of enterococcal
      bacteremia in our neonatal intensive care unit than there were in the previous
      decade. The characteristics associated with these infections were similar to
      those occurring with other nosocomial bacterial infections in the neonate and did
      not change during the period reviewed. Most recent episodes occurred as part of
      polymicrobial infections in newborns hospitalized for more than 1 month.
      Infections caused by vancomycin-resistant enterococci occurred in older patients
      but were clinically indistinguishable from infections caused by sensitive
      organisms.

PMID- 8878226
TI  - Streptococcal diagnostic testing and antibiotics prescribed for pediatric
      tonsillopharyngitis.
AB  - BACKGROUND: This study examined a 1-year cross-sectional sample of Kentucky
      Medicaid claims for the use of streptococcal diagnostic tests for pediatric
      tonsillopharyngitis and the empiric use of antibiotics. METHODS: Subjects were
      individuals older than 3 and younger than 18 years old seen in an ambulatory
      setting for tonsillopharyngitis; 3478 individuals accounted for the 5067 separate
      outpatient and emergency room encounters for pediatric tonsillopharyngitis; 849
      encounters coded as streptococcal sore throat were also examined. RESULTS:
      Diagnostic tests for group A streptococcal tonsillopharyngitis were performed in
      only 22% (n = 1130) of the tonsillopharyngitis encounters and 36% (n = 306) of
      the streptococcal sore throat encounters. Urban physicians were more likely than
      rural physicians to use a diagnostic test (P = 0.0001). Emergency room encounters
      and outpatient encounters were not significantly different in the likelihood of
      having a diagnostic test (P = 0.16). In encounters for tonsillopharyngitis
      antibiotics were prescribed in 72% of the total encounters and in 73% of the
      encounters without a diagnostic streptococcal test. In encounters for
      streptococcal sore throat, antibiotics were prescribed for 68% of the total
      encounters and 69% of the encounters without a diagnostic streptococcal test.
      CONCLUSIONS: Current practices in the Kentucky Medicaid program do not follow the
      American Academy of Pediatrics guidelines for streptococcal tonsillopharyngitis.

PMID- 8878227
TI  - The discovery of penicillin.

PMID- 8878228
TI  - Human immunodeficiency virus type 1 infection of the heart in three infants with
      acquired immunodeficiency syndrome and sudden death.

PMID- 8878229
TI  - Herpes simplex virus type 1 meningitis.

PMID- 8878230
TI  - Mycoplasma pneumoniae pericarditis and cardiac tamponade in a ten-year-old girl.

PMID- 8878231
TI  - Genomic fingerprinting by pulsed field gel electrophoresis to identify the source
      of Pasteurella multocida sepsis.

PMID- 8878232
TI  - Aspergillus osteomyelitis in chronic granulomatous disease: treatment with
      recombinant gamma-interferon and itraconazole.

PMID- 8878233
TI  - Drug-resistant tuberculosis verrucosa cutis in a Southeast Asian teenager.

PMID- 8878234
TI  - Possible hazards of routine bacillus Calmette-Guerin immunization in human
      immunodeficiency virus-infected children.

PMID- 8878235
TI  - Typhoidal tularemia in a human immunodeficiency virus-infected adolescent.

PMID- 8878236
TI  - Fever, leukocytosis and skin ulcerations in a four-month-old male. Leukocyte
      adhesion deficiency (LAD).

PMID- 8878237
TI  - Structured guidelines for the use of influenza vaccine among children.

PMID- 8878238
TI  - Teratogenicity of fluconazole.

PMID- 8878239
TI  - Incidence of antibiotic-resistant Streptococcus pneumoniae and beta-lactamase
      positive Haemophilus influenzae in clinical isolates from patients with otitis
      media.
AB  - BACKGROUND: The prevalence of penicillin-resistant Streptococcus pneumoniae and
      beta-lactamase-producing Haemophilus influenzae in otitis media infections is
      increasing; emergence of these pathogens has complicated treatment. OBJECTIVES:
      To evaluate the incidence of penicillin resistance and the in vitro activity of
      amoxicillin/clavulanate, cefaclor, loracarbef, cefixime,
      trimethoprim/sulfamethoxazole, azithromycin and clarithromycin in S. pneumoniae
      isolates. The in vitro activity of azithromycin, clarithromycin and cefaclor was
      also evaluated in beta-lactamase-positive and -negative isolates of H.
      influenzae. METHODS: Bacterial isolates of S. pneumoniae and H. influenzae were
      obtained by tympanocentesis and subsequent culture of middle ear effusion from
      children with acute otitis media enrolled in a multicenter trial. Susceptibility
      to test agents was assessed by disk diffusion and broth dilution techniques with
      criteria established by the National Committee for Clinical Laboratory Standards.
      RESULTS: Nineteen (31%) of the 61 S. pneumoniae isolates were resistant to
      penicillin. A significantly lower percentage of the S. pneumoniae isolates were
      resistant to azithromycin (16%) and clarithromycin (11%) than to penicillin,
      amoxicillin/ clavulanate, cefaclor, loracarbef or cefixime (31% in all cases).
      Azithromycin was also more active than cefaclor and significantly more active
      than clarithromycin against the 55 H. influenzae isolates. CONCLUSIONS: The
      susceptibility of resistant and nonresistant strains of S. pneumoniae to
      azithromycin and clarithromycin and of isolates of H. influenzae to azithromycin,
      coupled with penetration of azithromycin into the middle ear, may provide a
      significant advantage in the treatment of otitis media.

PMID- 8878240
TI  - A multicenter, open label trial of azithromycin for the treatment of children
      with acute otitis media.
AB  - OBJECTIVE: In this multicenter, open label trial the investigators evaluated the
      efficacy and safety of azithromycin suspension administered once daily for 5 days
      for the treatment of clinically and bacteriologically established acute otitis
      media. METHODS: Two hundred eligible children with acute otitis media from 10 US
      centers were treated with 10 mg/kg of azithromycin oral suspension on Day 1,
      followed by 5 mg/kg once daily for the next 4 days. Tympanocentesis and
      subsequent culture of middle ear effusion were performed at baseline. Clinical
      efficacy was evaluated on Days 6, 11 and 30. RESULTS: Analysis of clinical
      efficacy in evaluable patients 11 days after the initiation of therapy showed
      that the rate of satisfactory responses (cured or improved) ranged from 79.6 to
      82.4% in patients infected with Streptococcus pneumoniae, Haemophilus influenzae,
      or Moraxella catarrhalis. Satisfactory clinical response at Day 30 was reported
      in 70% of evaluable patients, and eradication of S. pneumoniae, H. influenzae and
      M. catarrhalis was presumed in 64 to 73%. Relapses occurred in 14% of the
      evaluable patients. Among the treated patients 8.5% reported mild or moderate
      side effects. CONCLUSION: Azithromycin is an effective, safe and well-tolerated
      treatment for children with acute otitis media.

PMID- 8878241
TI  - A multicenter, open label trial of azithromycin vs. amoxicillin/ clavulanate for
      the management of acute otitis media in children.
AB  - OBJECTIVE: This randomized, open label study compared the efficacy and safety of
      a 5-day course of once daily azithromycin to those of a 10-day course of three
      times daily amoxicillin/ clavulanate. METHODS: One hundred sixty-nine children
      with confirmed acute bacterial otitis media were randomized to treatment with 10
      mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily
      for the next 4 days or 40 mg/kg/ day of amoxicillin/clavulanate suspension in
      three divided doses for 10 days. Clinical efficacy and safety were evaluated on
      Days 11 and 30. RESULTS: Analysis of evaluable patients 11 days after the start
      of treatment demonstrated that 87.8% of patients treated with azithromycin and
      100.0% of the patients treated with amoxicillin/ clavulanate were cured or
      improved. Presumed bacteriologic eradication of the baseline pathogens
      Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and
      Streptococcus pyogenes was comparable in the two groups: 87.8% in patients
      treated with azithromycin; and 100.0% in patients receiving
      amoxicillin/clavulanate. At Day 30, 82.2% of patients treated with azithromycin
      and 80.0% of patients treated with amoxicillin/clavulanate were cured or
      improved. Presumed bacteriologic eradication of the base-line pathogens was
      similar in the two groups: 82.2% in patients treated with azithromycin; and 81.1%
      in patients receiving amoxicillin/clavulanate. Relapses occurred in 5.1% of
      patients receiving azithromycin and 21.1% of patients taking
      amoxicillin/clavulanate (P = 0.047). Treatment-related side effects occurred in
      3.5% of the azithromycin patients compared with 31.0% of amoxicillin/clavulanate
      patients (P < 0.001). CONCLUSIONS: Azithromycin was comparable to
      amoxicillin/clavulanate in achieving clinical cure or improvement and presumed
      eradication of baseline pathogens in pediatric patients with acute otitis media.
      Azithromycin was significantly better tolerated and was associated with fewer
      relapses than seen after amoxicillin/clavulanate therapy.

PMID- 8878242
TI  - A multicenter, double blind comparison of azithromycin and amoxicillin/
      clavulanate for the treatment of acute otitis media in children.
AB  - OBJECTIVE: To compare the efficacy and safety of azithromycin and
      amoxicillin/clavulanate in pediatric acute otitis media. METHODS: Investigators
      from 12 US centers recruited 677 children. In a randomized, double blind, double
      dummy fashion, participants received either azithromycin suspension (n = 341)
      once daily for 5 days or amoxicillin/clavulanate suspension (n = 336) in three
      divided doses daily for 10 days. RESULTS: Among evaluable patients satisfactory
      clinical response rates (cured and improved) measured 11 days after therapy began
      were 87.5% in the azithromycin group and 87.9% in the amoxicillin/clavulanate
      group; corresponding rates at 30 days were 73.5% in the azithromycin and 71.2% in
      the amoxicillin/clavulanate groups. Relapse rates were comparable for the
      treatment groups. Treatment-related side effects, primarily gastrointestinal,
      were reported significantly less frequently with azithromycin (8.8%) than with
      amoxicillin/clavulanate (30.8%) (P < 0.0001). Two (0.6%) azithromycin patients
      and 12 (3.6%) amoxicillin/ clavulanate patients discontinued therapy because of
      treatment-related side effects (P < 0.006 between groups). CONCLUSIONS: In these
      children with acute otitis media, azithromycin given once daily for 5 days and
      amoxicillin/clavulanate given three times daily for 10 days had similar efficacy;
      however, azithromycin was significantly better tolerated.

PMID- 8878244
TI  - Properties of azithromycin that enhance the potential for compliance in children
      with upper respiratory tract infections.
AB  - BACKGROUND: Azithromycin, the prototypical azalide antibiotic, has a wide
      spectrum of activity that is characterized by resistance to beta-lactamase
      producing microbes and efficacy against Gram-positive and Gram-negative
      pathogens, including Haemophilus influenzae. Tissue-directed pharmacokinetics
      include tissue concentrations up to 100-fold higher than those in plasma and a
      tissue half-life of up to 4 days. Pharmacokinetics of azithromycin permits a
      reduction in dosage frequency and duration while maintaining efficacy comparable
      to that of conventional 7- to 10-day three or four times daily regimens. Dosage
      interval, duration of treatment, side effects and palatability can affect
      compliance and thus clinical outcome. Compliance among children is important in
      light of the high incidence of community-acquired infections such as otitis media
      and streptococcal pharyngitis. OBJECTIVE: To compare the flavor, taste
      acceptability and color preference of oral antibiotic suspensions given to
      children. METHODS: The taste and acceptability of the oral suspension form of
      azithromycin vs. cefixime, cefpodoxime proxetil, cefprozil, clarithromycin or
      loracarbef were rated by children during blinded taste tests and with
      acceptability/ preference questionnaires. RESULTS: Analysis of the mean
      acceptability/ preference rating from 769 children demonstrated that the flavor
      of azithromycin was rated significantly higher than that of cefpodoxime (4.3 vs.
      2.8), cefprozil (4.0 vs. 3.4) and clarithromycin (4.3 vs. 2.7) and was comparable
      to that of cefixime (4.0 vs. 4.2) and loracarbef (4.4 vs. 4.5). A greater
      percentage of children preferred the taste of azithromycin to that of cefpodoxime
      (90.0% vs. 5.2%), cefprozil (63.0% vs. 33.1%) and clarithromycin (89.0% vs.
      11.0%). The taste of azithromycin was not preferred to that of cefixime (39.0%
      vs. 53.9%) or loracarbef (36% vs. 58.5%). CONCLUSIONS: The efficacy and safety of
      azithromycin in otitis media and streptococcal pharyngitis, the simple dosing
      regimen and a highly palatable oral suspension formulation should increase
      compliance among pediatric patients and thereby improve clinical outcomes.

PMID- 8878243
TI  - A multicenter, randomized, open label comparison of azithromycin and
      amoxicillin/clavulanate in acute otitis media among children attending day care
      or school.
AB  - OBJECTIVE: This multicenter, randomized, open label study compared the efficacy
      and safety of azithromycin and amoxicillin/clavulanate for the treatment of acute
      otitis media among children who were attending a day-care facility or school.
      METHODS: Eligible children with acute otitis media from 21 US centers were
      randomized to treatment with 10 mg/kg of azithromycin oral suspension on Day 1,
      followed by 5 mg/kg once daily for the next 4 days or approximately 40 mg/kg/day
      of amoxicillin/clavulanate suspension in 3 divided doses for 10 days. Clinical
      efficacy was evaluated on Days 14, 30 and 45. Acceptance and convenience of the
      medications were assessed on Day 14 by parent interviews with a standardized
      questionnaire. RESULTS: Of the 263 children enrolled in the study, 233 were
      evaluable at the primary evaluation 45 days after the start of treatment.
      Satisfactory clinical response rates (cure, delayed cure and improvement) were
      60.5% in patients treated with azithromycin and 64.9% in patients treated with
      amoxicillin/clavulanate. Satisfactory clinical response rates at secondary
      evaluations were also comparable: 92.2% vs. 90.0% at Day 14 and 66.7% vs. 72.7%
      at Day 30 in patients treated with azithromycin and amoxicillin/clavulanate,
      respectively. No significant differences in treatment failures, relapses or
      recurrences were noted with either medication. Azithromycin was significantly
      better tolerated and caused fewer treatment-related adverse events (7.2%) than
      amoxicillin/clavulanate (17.1%) (P < 0.001). In response to the interview and
      questionnaire, parents of children treated with azithromycin noted less need for
      special arrangements to give medication (2.0% vs. 14.9%). Children liked the
      taste of azithromycin (89.2%) and did not have to be forced to take the
      medication (2.4%). Parents of children receiving amoxicillin/clavulanate noted
      that 61.8% liked the medication and 19.4% of children had to be forced to take
      it. CONCLUSIONS: This study demonstrates that azithromycin was comparable to
      amoxicillin/clavulanate in achieving satisfactory clinical response rates in
      children with acute otitis media attending day care or school. Azithromycin was
      significantly better tolerated than amoxicillin/ clavulanate. Parents considered
      azithromycin to be significantly more convenient to administer and more
      acceptable to children.

PMID- 8878245
TI  - Reverse cholesterol transport in the rat following a short-term intravenous
      infusion of fat emulsion.
AB  - The effect on cholesterol transport of an intravenous infusion of a fat emulsion
      (10%) Intralipid or 10% Lipovenos) in vivo was investigated in the rat.
      Intralipid (1.85 ml/hr/kg body weight in rts for 3 hr) caused a reduction (P <
      0.05) in free cholesterol in the aorta (by 25%), in plasma high-density
      lipoproteins (64%) and in erythrocytes (11%) with a concomitant enrichment of
      liver free cholesterol (16%), suggesting an enhanced reverse cholesterol
      transport in this species. Lipovenos under the same conditions gave similar
      results. Our data support our previous in vivo study in man indicating that
      infusion of a fat emulsion is able even to remove cholesterol from the arterial
      wall and thereby possibly be considered as an antiatherosclerotic agent.

PMID- 8878246
TI  - Influence of biochemical parameters of liver function on vancomycin
      pharmacokinetics.
AB  - The influence of biochemical parameters of hepatic function on vancomycin
      pharmacokinetics was retrospectively evaluated in 76 adult patients (age 18 to 81
      years), from biochemistry data gathered during routine therapeutic drug
      monitoring. All subjects had normal serum creatinine levels. Vancomycin
      concentrations were determined by fluorescence polarization immunoassay in 101
      paired serum samples. All data for vancomycin concentration versus time were
      fitted to a one-compartment model using the bayesian approach. Bilirubin,
      transaminases (n = 101), gamma-glutamyl transferase (n = 97), alkaline
      phosphatase (n = 95), albumin (n = 92) and lactate dehydrogenase (n = 42) were
      determined. No strong correlation was seen between any of the pharmacokinetic and
      biochemistry parameters studied. In patients with hyperbilirubinaemia, the mean
      Vss and t1/2 were increased (Vss: 0.75 +/- 0.31 versus 0.92 +/- 0.42 1.kg-1, p =
      0.020; t1/2 5.93 +/- 3.30 versus 7.48 +/- 4.44 hr, p = 0.049). When liver
      function was evaluated according to hepatic profile (normal, mildly altered and
      severely altered), no significant differences were observed in vancomycin
      pharmacokinetics among the groups. In conclusion, vancomycin pharmacokinetics are
      only weakly influenced by the biochemistry parameters of liver function.

PMID- 8878247
TI  - Elimination of recently absorbed methyl mercury depends on age and gender.
AB  - The toxicokinetics of some toxic metals have been demonstrated to depend on the
      age of the exposed individuals. Most studies focused solely upon age-dependent
      differences in degree of absorption. The present study aimed at investigating
      possible age-dependent differences in elimination of CH3HgCl using 203Hg and
      repeated whole-body counting of live mice to quantitate the whole-body retention.
      With increasing age at the time of exposure to a single oral dose of CH3HgCl, the
      rate of elimination more than doubled in male mice. As intestinal absorption of
      CH3HgCl is almost complete, the findings must pertain either to an age-related
      increased excretion capacity or an age-dependent change in the excretion
      mechanism. To study whether saturation of the excretion mechanism could explain
      this observation, groups at different age were supplemented with non-labeled
      CH3HgCl in the drinking water during a two weeks observation period after
      administration of a single dose of CH3203HgCl. Supplementation did not influence
      the rate of elimination of CH3HgCl in mature males. Accordingly, the mechanism
      causing the observed age-dependent change in elimination rate is not a matter of
      saturation but an age-dependent development of a more efficient mechanism for
      CH3HgCl elimination. Further, as elimination of mercury absorbed during a
      prolonged period of exposure through drinking water was not influenced by age,
      the critical step for the age-dependent mechanism for elimination of CH3HgCl
      seems to be the initial absorption and distributional phase after exposure and
      most likely involves the hepatic handling of methyl mercury.

PMID- 8878248
TI  - Effects of eicosapentaenoic acid and docosahexaenoic acid diet supplement on
      tolerance to the cardiotoxicity of epirubicin and to ischaemia reperfusion in the
      isolated rat heart.
AB  - We compared the effects of 2 weeks dietary supplement of docosahexaenoic acid,
      eicosapentaenoic acid or olive oil on myocardial tolerance to the cardiotoxicity
      of the anthracycline epirubicin and to ischaemia reperfusion. Isolated rat hearts
      from the dietary groups were perfused at a constant flow rate of 12.5 ml/min. The
      hearts were subjected to a 20 min. period of epirubicin infusion by a side arm of
      the perfusion system at a rate of 0.2 mg/min. or a 20 min. period of global
      ischaemia. After 10 min. of epirubicin infusion a significantly (P < 0.05) higher
      aortic pressure (an index of coronary resistance during constant flow perfusion)
      was observed in the olive oil group; 130 +/- 22% (mean +/- S.D.) compared to
      hearts in the docosahexaenoic acid; 108 +/- 9% (mean +/- S.D.), and
      eicosapentaenoic acid; 105 +/- 7% (mean +/- S.D.), group. Hearts from
      docosahexaenoic acid-fed rats showed a significantly increased left ventricular
      end-diastolic pressure (an index of contracture); of 66 +/- 30 mmHg (mean +/-
      S.D.) after 15 min. of global ischaemia compared to eicosapetaenoic acid fed
      rats; 37 +/- 18 mmHg (mean +/- S.D.), and significantly higher release of lactate
      dehydrogenase during the following 30 min. period of reperfusion compared to
      olive oil-fed rats. We conclude that eicosapentaenoic acid and docosahexaenoic
      acid could be useful during epirubicin infusion and that docosahexaenoic acid
      could be harmful during ischaemia reperfusion.

PMID- 8878249
TI  - Functional characterization of endothelin receptors in the bovine retractor penis
      muscle and penile artery.
AB  - The effects of endothelin-1 and sarafotoxin 6c on the bovine retractor penis
      muscle and the bovine penile artery were studied, and a functional
      characterization of endothelin receptors in these tissues was performed by using
      the ETA-receptor antagonist BQ-123 and the ETB-receptor antagonist IRL 1038. The
      retractor penis muscle and the penile artery were about equipotently contracted
      by endothelin-1 in a concentration-dependent manner the EC50 values being 3.5 x
      10(-9) M and 1.3 x 10(-9) M, respectively. In both tissues BQ-123 (10(-6) M)
      inhibited maximal contraction induced by endothelin-1 by about 50%. Sarafotoxin
      6c substantially relaxed the retractor penis muscle, and to a lesser extent also
      the penile artery, whereas endothelin-1 did not relax either tissue. The
      sarafotoxin 6c-induced relaxation of the retractor penis muscle was totally
      inhibited by IRL 1038 (3 x 10(-6) M) and the nitric oxide synthase inhibitor L
      NNA (10(-4) M). In both tissues L-NNA enhanced the contraction induced by
      endothelin-1 and lowered the threshold concentration for it. The results show
      that in both tissues the contraction induced by endothelin-1 was mediated
      primarily by ETA-receptors. The retractor penis muscle is also equipped with ETB
      receptors, probably at least in part located on the inhibitory nerves, which
      mediate relaxation via activation of the L-arginine nitric oxide synthase
      pathway.

PMID- 8878250
TI  - Distribution of glutathione S-transferase isoforms in rat liver after induction
      by beta-naphthoflavone or 3-methylcholanthrene.
AB  - Regional differences in vulnerability to xenobiotic liver damage may relate to
      the distribution of the detoxication capacity of the glutathione S-transferases
      (GST). HPLC analysis of cell lysates obtained by digitonin infusion from either
      the periportal or the perivenous region revealed that the content of all the GST
      subunits investigated (1, 2, 3, 4 and 8) was higher in the perivenous region. The
      strongest perivenous dominance was observed for subunit 1 (Ya) and the alpha
      class appeared to be more zonated that the mu class. A similar perivenous
      dominance was observed by analysis of GST activity with either 1-chloro-2,4
      dinitrobenzene (CDNB), 1,2-dichloronitrobenzene (DCNB) or trans-4-phenyl-3-buten
      2-one (PBO) as substrate. In contrast, with cumene hydroperoxide (CuOOH) or tert
      butyl hydroperoxide (tBOOH) as substrate a reciprocal twofold periportal
      dominance was observed. Induction by pretreatment with beta-naphthoflavone
      reduced or abolished the perivenous dominance of the alpha-subunits 1, 2 and 8.
      In contrast, after pretreatment with 3-methylcholanthrene, only the acinar
      gradient of subunits 2 (Yc) was abolished, while the strong perivenous gradient
      subunit 1 (Ya) was maintained and that of subunit 8 (Yk) increased. CDNB based
      assays demonstrated that beta-naphtoflavone treatment reduced (from 2.1 to 1.4)
      while 3-methyl cholanthrene enhanced (to 2.6) the perivenous/periportal GST
      activity ratio. Assays based on CuOOH or tBOOH indicated that neither the Se
      dependent nor the Se-independent glutathione peroxidase activity nor its acinar
      distribution was affected by the inducers. These results demonstrated that
      although the expression of all investigated members of the alpha and mu classes
      is higher in the perivenous region, there are marked isozyme differences, the
      acinar gradient being particularly prominent for subunit 1 (Ya). The distinct
      difference in the acinar induction pattern of GST Ya between beta-naphthoflavone
      and 3-methylcholanthrene resembles that reported for cytochrome P450 (CYP1A1 and
      CYP1A2), also members of the aryl hydrocarbon (Ah) receptor genes, suggesting
      common regionally acting regulatory elements in the expression of these genes in
      the liver.

PMID- 8878251
TI  - Lithium and valproate combined administration: acute behavioural effects and drug
      plasma levels.
AB  - Drug plasma concentrations and behavioural effects of acute combined
      administration of lithium and valproic acid were studied in normonatraemic and
      hyponatraemic rats. Hyponatraemia was induced two hours before drug
      administration and behavioural observations lasted for two additional hours.
      Blood was collected by the end of the behavioural observation. The higher doses
      of valproic acid (360 mg/kg) or lithium (2 mEq/kg) induced more head-shakes and
      higher plasma concentration than 180 mg/kg of valproic acid or lithium 1 mEq/kg,
      respectively. Valproic acid and lithium administered separately induced more head
      shakes and higher drug plasma levels in hyponatraemic rats than in normonatraemic
      animals. Combined administration of valproic acid (180 mg/kg) and lithium (2
      mEq/kg) produced a supra-aditive effect in head-shakes. The drug interaction
      between lithium and valproic acid induced a decrease in valproic acid plasma
      level and an increase in lithium plasma levels.

PMID- 8878253
TI  - Effects of dexamethasone on sleep.
AB  - The purpose of this study was to evaluate the effects of acute systemic
      corticosteroid administration on sleep structure in healthy individuals. We
      conducted a randomized, prospective, double-blind, placebo-controlled cross-over
      study of the effects of dexamethasone, 3 mg every eight hours for 48 hr on the
      sleep architecture of six normal volunteers (mean age 28 years, five males and
      one female). The subjects were participants blood pressure. Each subject was
      studied with a full polysomnogram on two successive nights when receiving either
      placebo or dexamethasone. Only the second night was used for analysis. Placebo
      and dexamethasone periods were separated by at least two weeks. There were
      significant increases in the REM latency, percent time spent awake and percent
      time spent in slow wave sleep in subjects taking dexamethasone when compared to
      their sleep while taking placebo. There were also significant decreases in the
      percent time spent in REM and the number of REM periods while on dexamethasone.
      We conclude that pharmacologic doseas of dexamethasone alter sleep architecture
      in healthy humans.

PMID- 8878252
TI  - Uptake of 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene in melanin-containing
      tissues.
AB  - It is widely accepted that UV exposure is the main etiological factor for
      malignant melanoma. Epidemiologic studies, however, have indicated that also
      chemical carcinogens may be a risk factor for the disease. Polycyclic aromatic
      hydrocarbons such as 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene represent
      an important class of carcinogenic chemicals. It is known that 7,12
      dimethylbenz(a)anthracene can induce melanotic tumours in various animal species,
      and human melanocytes in culture have been found to be capable of metabolizing
      benzo(a)pyrene to its proximate carcinogen benzo(a)pyrene-7,8-diol. In the
      present study the disposition of 14C- and 3H-7,12-dimethylbenz(a)anthracene and
      14C-benzo(a)pyrene was studied in pigmented and albino mice and Syrian golden
      hamsters by whole-body autoradiography. The results showed pronounced retention
      of label in the melanin-containing structures of the eyes and the hair follicles
      in the pigmented animals. The labelling of the corresponding structures in the
      albino animals was low. Additional experiments showed that 7,12
      dimethylbenz(a)anthracene and benzo(a)pyrene as well as some of their metabolites
      are bound to melanin in vitro. The specific localization of the polycyclic
      aromatic hydrocarbons in pigmented tissues due to melanin affinity, combined with
      bioactivating capacity of melanocytes, suggest that these substances may play a
      role in the induction of malignant melanoma.

PMID- 8878254
TI  - The mu1 and mu2 opioid receptor binding of ketobemidone, norketobemidone and 3
      dimethylamino-1,1-diphenylbutene.

PMID- 8878255
TI  - Solid-phase extraction and HPLC analysis of kebuzone and its metabolites in
      blood.
AB  - A HPLC method for quantification of kebuzone and its metabolites in whole blood
      was developed. The compounds and the internal standard were isolated from blood
      by solid-phase extraction on a C-18 cartridge. A blood sample was to be hemolyzed
      before extraction. HPLC was performed on a C-18 column with the mobile phase
      composed of methanol/water acidified to pH 2.7 and UV absorbance detection at 247
      nm. This method has been successfully applied to a pharmacokinetic study of
      kebuzone and its metabolites in rabbits.

PMID- 8878256
TI  - Effects of quinazoline (3H, 1H)-4-one-2-thiones with axial and central chirality
      on the contractile response of smooth muscle.
AB  - Quinazolines are versatile nitrogen heterocyclic compounds displaying a broad
      spectrum of biological and pharmacological activities. The influence of some new
      synthesized quinazolines with axial and central chirality was studied on the
      isometric muscle tension of rat ileum, rat uterus, and porcine coronary artery.
      While structural changes of the compounds showed only little influence on
      peristaltic movement of the ileum, quinazoline derivatives induced a relaxation
      in the uterus and in the coronary artery depending on the kind and position of
      the substituent. The introduction of axial chirality into the molecule of
      modification of the side chain caused an increase in the pharmacological action.
      These effects could not be inhibited by sympatholytics. So far the mechanisms and
      receptors causing the spasmolysis are unknown.

PMID- 8878257
TI  - Inhibition of chemiluminescence response of human mononuclear cells and
      suppression of mitogen-induced proliferation of spleen lymphocytes of mice by
      hispolon and hispidin.
AB  - The effects of two phenolic compounds, hispolon and hispidin isolated from fruit
      bodies of the basidiomycete Inonotus hispidus (Bull. ex Fr.) Karst, were
      investigated on the chemiluminescence response by LPS- or zymosan-activated human
      mononuclear cells (MNC) and on the concanavalin A-induced proliferation of spleen
      lymphocytes of mouse in vitro. Both compounds showed inhibitory activity in the
      chemiluminescence-test with an IC50 (the concentration of test compound causing
      50% effect) ranging from 4.4 to 4.6 micrograms/ml (20.3 to 21.2 microM) for
      hispolon and < 0.1 to 1.5 micrograms/ml (from < 0.4 microM to 6.0 microM) for
      hispidin. Antiproliferative effects have been achieved in the lymphocyte
      transformation test (LTT) by hispolon with an IC50 of 3.4 micrograms/ml (15.5
      microM).

PMID- 8878258
TI  - Stroke therapy becomes reality.

PMID- 8878259
TI  - Extinction rates can be estimated from molecular phylogenies.
AB  - Molecular phylogenies can be used to reject null models of the way we think
      evolution occurred, including patterns of lineage extinction. They can also be
      used to provide maximum likelihood estimates of parameters associated with
      lineage birth and death rates. We illustrate: (i) how molecular phylogenies
      provide information about the extent to which particular clades are likely to be
      under threat from extinction; (ii) how cursory analyses of molecular phylogenies
      can lead to incorrect conclusions about the evolutionary processes that have been
      at work; and (iii) how different evolutionary processes leave distinctive marks
      on the structure of reconstructed phylogenies.

PMID- 8878260
TI  - Close linkage relationship of the Z-linked pop-eye and silver plumage color loci
      in the chicken.
AB  - The Z-linked pop-eye and the silver plumage color loci in the chicken were tested
      for linkage using a back cross. The F1 males used were silver, with normal eyes
      and gold down, pop-eye in coupling (*S *N/*G *POP). The females were gold, pop
      eye (*G *POP/W). In previous studies, it had been suggested that both loci were
      on the short arm of the Z chromosome. There were 13 recombinants among 187
      individuals obtained from this mating, indicating that these loci are linked by
      about 7 cM.

PMID- 8878261
TI  - The effect of broiler breeder flock age and length of egg storage on egg albumen
      during early incubation.
AB  - The objective of these two experiments was to determine the temporal changes in
      albumen during storage and early incubation as a means of understanding some of
      the effects of egg storage on early embryonic development. Eggs from 30- or 50-wk
      old broiler breeder hens were incubated (37.5 C dry bulb, 30 C wet bulb) after
      storage for 0 (fresh) or 5 d (18 C, 75% RH) in Experiment 1. Albumen height,
      albumen pH, and egg weight loss were recorded at 2, 24, 48, and 66 h of
      incubation. The same measurements were taken on another group of eggs from 43-wk
      old hens stored for 0 (fresh), 4, 8, or 12 d in Experiment 2. All hens were of
      the same strain. Egg weight loss during incubation was significantly greater in
      fresh eggs than in stored eggs in Experiment 1. Fresh eggs had significantly
      greater albumen height and significantly lower albumen pH than stored eggs in
      both experiments. These differences diminished with length of incubation. Because
      the blastoderm is located adjacent to the albumen, changes in the viscosity or pH
      of the albumen may play an integral role in determining the viability of the
      embryo during the very early stages of development. Incubation of fresh eggs
      without storage appears to expose the developing embryo to an inappropriate trans
      vitelline membrane pH gradient and a thick albumen that may slow vital gas
      diffusion and limit nutrient availability. These conditions may cause an
      increased incidence of embryonic death.

PMID- 8878262
TI  - Influence of dietary concentration and source of meat and bone meal on
      performance of turkeys.
AB  - Two experiments were conducted to determine the influence of dietary
      concentration and source of meat and bone meal (MBM) on performance of tom
      turkeys from 1 to 119 d of age. In Experiment 1, six replicate pens of toms were
      fed diets containing 0, 3, 6.5, or 10% MBM. Feeding up to 10% MBM resulted in 119
      d BW and feed to gain ratios (F:G) equal to those of toms fed the diet containing
      no MBM (14.09 kg per tom, F:G = 2.68 for 10% MBM vs 14.08 kg per tom and F:G =
      2.70 for the control). Five MBM were evaluated at 10% of the diet in Experiment
      2. These MBM differed in source material and proportions of source material
      (beef, poultry, or pork processing by-products) from which they were made. As
      compared with feeding a diet containing no MBM, feeding diets with 10% of any of
      the MBM supported satisfactory 119-d BW and F:G. The data show that up to 10%
      dietary MBM obtained from different sources can be used successfully for growing
      turkeys when diets are formulated by using CP, amino acid, Ca, and P data for MBM
      obtained by laboratory analysis and the MEn value listed for MBM in NRC (1994).

PMID- 8878263
TI  - Effect of dietary methionine intake on egg component yield and composition.
AB  - The effects of methionine intake on liquid egg component yield and composition
      were examined in two laying hen experiments using diets supplemented with
      differing levels of methionine. In Experiment 1, a high methionine intake level
      of 512 was compared to 326 mg per hen-day (HD). The 512 mg/HD intake
      significantly increased egg weight, component mass, and total solids in both
      albumen and yolk. Experiment 2 examined methionine intakes of 328, 354, 392, and
      423 mg/ HD. There were no significant differences in egg weight, component yield,
      or egg production among the treatments. Albumen solids from the 423 mg/HD intake
      level were significantly elevated when compared to 328 and 354 mg/HD. A
      methionine consumption of 354 mg/HD resulted in significantly lower yolk solids
      than 328, 392, and 423 mg/HD. Methionine intakes of 392 and 423 mg/HD did result
      in significantly increased crude protein content of albumen and yolk compared to
      328 and 354 mg/HD methionine. Experiment 1 found elevated dietary methionine
      increased egg size, component mass, and solids content of albumen and yolk.
      Experiment 2 methionine intake significantly increased crude protein of albumen
      and yolk without changes in egg size or component yield. These results indicate a
      methionine intake range that will later liquid component composition while egg
      size remains unchanged.

PMID- 8878264
TI  - Studies on the feeding of cupric sulfate pentahydrate and cupric citrate to
      broiler chickens.
AB  - Male commercial broiler strain chickens were fed either a control diet (based on
      corn and soybean meal) or the control diet supplemented with cupric sulfate
      pentahydrate or cupric citrate in seven experiments (six in floor pens, one in
      wire-floored batteries). In Experiment 1, feeding 125 or 250 mg/kg copper
      increased growth (4.9%) and decreased feed conversion ratios (3.4%), total plasma
      cholesterol (40.2%), and breast muscle cholesterol (37.0%). Feeding 375 mg/kg
      copper was without further beneficial effect. In Experiment 2, withdrawing growth
      promoting supplements of copper from the feed for the last 7 d caused a
      significant (P < 0.05) increase in breast muscle cholesterol at 42 d of age:
      57.2, 48.0, and 43.2 mg/100 g meat for birds supplemented for 0, 35, or 42 d,
      respectively. Feeding 10 vs 260 mg/kg copper caused only small increases in
      tissue copper levels: 0.36 vs 0.41 mg/kg for breast meat, and 0.48 vs 0.60 mg/kg
      for thigh meat, respectively. Litter copper accumulations in these experiments
      were similar to those of earlier reports. Breast muscle cholesterol was reduced
      by feeding 125 mg/kg supplemental copper from cupric citrate (27.84 mg/100 g) or
      125 mg supplemental copper from cupric sulfate pentahydrate (25.32 mg/100 g)
      compared to broilers fed the control diet (43.92 mg/100 g). Cupric citrate was
      efficacious for growth promotion at lower copper levels than cupric sulfate
      pentahydrate, resulting in reduced litter copper.

PMID- 8878265
TI  - Effect of beta-carotene, canthaxanthin, lutein, and vitamin E on neonatal
      immunity of chicks when supplemented in the broiler breeder diets.
AB  - The study was designed to assess neonatal immunity of chicks hatched from
      breeders fed diets supplemented with beta-carotene, canthaxanthin, lutein, or
      vitamin E. Broiler breeder birds were fed experimental diets consisting of
      control, 0.04% beta-carotene, 0.04% canthaxanthin, 0.04% lutein, 0.03% alpha
      tocopherol acetate, or 0.04% beta-carotene plus 0.03% alpha-tocopherol acetate.
      Three weeks after initiation of experimental feeding, birds were vaccinated
      against Newcastle disease virus. Chicks hatched from the eggs of these breeders
      were used to determine the neonatal immune responses. There were no significant
      differences in weight gain and antibody titers of 3-wk-old chicks. 3H-Thymidine
      uptake by bursal lymphocytes when stimulated with tetrahydrofuran was
      significantly higher for the chicks hatched from breeders fed diets supplemented
      with vitamin E, or vitamin E plus beta-carotene, than in controls. 3H-Thymidine
      uptake by splenic lymphocytes when stimulated with concanavalin A and phorbol 12
      myristate 13 acetate was significantly higher for the chicks hatched from
      breeders fed diets supplemented with vitamin E or beta-carotene alone, or vitamin
      E plus beta-carotene, than for the control chicks. Chicks hatched from hens
      supplemented with vitamin E had significantly higher antibody titers at 1 and 7 d
      of age than chicks from the control group. Vitamin E supplementation of breeder
      birds increased the immune response of their progeny.

PMID- 8878266
TI  - Additivity of apparent and true ileal amino acid digestibilities in soybean meal,
      sunflower meal, and meat and bone meal for broilers.
AB  - An experiment was conducted to determine the additivity of apparent and true
      ileal amino acid digestibility values in soybean meal (SBM), sunflower meal
      (SFM), and meat and bone meal (MBM). A total of 63 individually caged 5-wk-old
      broilers were assigned to seven groups and given semi-purified diets containing
      SBM, SFM, MBM, and their combinations. True digestibilities were estimated by
      using the homoarginine in guanidinated proteins as the marker. Additivity was
      tested by comparing the differences between the observed digestibilities of
      ingredient combinations and the predicted values from measurements with
      individual ingredients. In general, for both apparent and true digestibilities,
      there were no significant differences (P > 0.05) between the observed and
      predicted values in ingredient combinations. The only exception was SBM + MBM
      combination, in which the observed values for apparent digestibilities of
      aspartic acid, serine, glutamic acid, isoleucine, and tyrosine were significantly
      higher (P < 0.05) than the predicted values. Overall, the present results
      indicate that amino acid digestibility values are additive and that digestible
      amino acid supply in a complete diet can be predicted from amino acid
      digestibilities of individual ingredients.

PMID- 8878267
TI  - Intestinal uptake and metabolism of fatty acids in the chick.
AB  - Uptake and metabolism of fatty acids in the duodenal mucosa of the chick was
      studied. In vitro incubations of a mucosal homogenate with 14C-oleic acid
      indicated that together with glycerides, water-soluble 14C compounds and 14CO2
      were formed; the latter comprised approximately one quarter of metabolites
      formed. Studies in chickens introducing 14C-oleic acid into the duodenum and
      determining appearance of label in the cannulated pancreaticoduodenal vein and
      brachial artery indicated that similar processes occur in vivo, with both labeled
      glycerides and water-soluble compounds appearing in the blood. Quantitatively,
      metabolism of 14C-oleic acid to nonlipid compounds amounted to some 15% of the
      dose after 60 min. These findings suggest that a considerable portion of ingested
      fatty acids are metabolized before transport to the circulation.

PMID- 8878268
TI  - The effect of ethoxyquin on tissue peroxidation and immune status of single comb
      White Leghorn cockerels.
AB  - The responses to supplementing the diet of Single Comb White Leghorn (SCWL)
      cockerels with ethoxyquin were tested on two parameters: 1) tissue peroxidation
      and 2) immune response. In the first experiment, three concentrations of
      supplemental ethoxyquin (0, 500, and 1,000 ppm) were added to a basal diet and
      fed to SCWL cockerels for 6 wk. Tissue peroxidation was assessed by measuring the
      thiobarbituric acid reactive substances (TBARS) concentration in the liver,
      kidney, heart, and spleen. The TBARS concentration in response to 500 ppm dietary
      ethoxyquin was significantly lower in the liver and spleen tissues, whereas in
      the kidneys, 1,000 ppm ethoxyquin significantly lowered TBARS. In a second
      experiment, four concentrations of ethoxyquin (0, 125, 500, and 1,000 ppm) were
      added to a basal diet and fed to SCWL cockerels for 8 wk. The primary and
      secondary immune response were assessed by determining antibody titers to the
      Newcastle disease virus using hemagglutination inhibition (HI) and ELISA. The HI
      and ELISA titers for the primary and secondary immune response were not
      significantly different from the control. Analysis of body weight, feed
      conversion, and organ weight revealed no statistically significant differences
      between treatments, although in the second experiment the dietary treatment of
      1,000 ppm ethoxyquin resulted in significantly higher relative liver weight.

PMID- 8878269
TI  - A rapid, polymerase chain reaction-based procedure for identifying mutant
      restricted ovulator chickens.
AB  - Females of the restricted ovulator (RO) strain of White Leghorn chickens fail to
      lay eggs upon photostimulation and exhibit endogenous hyperlipidemia and
      atherosclerotic lesions. A mutation in the gene specifying the oocyte
      vitellogenesis receptor (OVR), a 95-kDa membrane protein that normally mediates
      the massive uptake of yolk precursors from the serum, is responsible for this
      abnormal phenotype. Because a single nucleotide substitution (G-->C) is
      responsible for the defective OVR, a PCR-based procedure, described herein, was
      developed in order to provide a rapid and accurate method for identifying
      chickens possessing the mutant allele. Polymerase chain reaction-amplified
      fragments of apparently identical size (approximately 400 bp) were obtained from
      genomic DNA using primer pairs specific for either the wild-type or mutant genes.
      Through cloning and sequencing of the PCR-amplified products, the fragment sizes
      were determined to be 413 bp each, which included an intron sequence. Polymerase
      chain reaction-amplified genomic DNA from wild-type (ovr+/ovr+) males,
      heterozygous carrier (ovr+/ovr-) males, and wild-type (-/ovr+) females all
      yielded a 413 bp fragment when a primer pair specific for the wild-type gene was
      used. Because female chickens are heterogametic (ZW), no PCR product was observed
      in the case of the mutant (-/ovr-) females. When the primer pair specific for the
      mutant gene was employed, PCR-amplification of genomic DNA from both heterozygous
      carrier (ovr+/ ovr-) males and mutant (-/ovr-) females, but not wild-type
      (ovr+/ovr+) males or (-/ovr+) females, also yielded a 413-bp fragment. Employment
      of the present rapid and accurate procedure would be expected to obviate the need
      for conventional progeny testing while reducing the time required to identify RO
      carrier males and mutant females from approximately 1 yr to several days.

PMID- 8878270
TI  - The effects of post-mortem electrical stimulation and muscle tensioning in two
      broiler muscles.
AB  - High voltage post-mortem electrical stimulation (ES) and muscle tensioning during
      chilling (MT) were applied to broiler carcasses to determine the effect of this
      combined treatment on absorbance ratio (R- value), sarcomere shortening, and
      myofibrillar fragmentation in muscles of differing fiber type composition. The ES
      + MT treatment resulted in a greater effect on these three parameters in the
      posterior Latissimus dorsi (predominantly twitch-glycolytic) than in the anterior
      L. dorsi (predominantly tonic-oxidative). The differing responses of these two
      muscles to the ES + MT treatment combination may be useful in explaining the
      effects of rigor-accelerating treatments such as ES + MT in avian and mammalian
      muscles.

PMID- 8878271
TI  - Introduction to egg pasteurization.
AB  - The science of microbiology is very young in comparison with the age of mankind.
      Related developments in the area of pasteurization have been made during the past
      131 yr. This symposium reveals some recent advancements in pasteurization of
      shell eggs and egg products.

PMID- 8878272
TI  - Pasteurization of eggs in the shell.
AB  - A small percentage of all eggs may be contaminated with Salmonella enteritidis
      (SE). To eliminate this hazard from the food supply, procedures for pasteurizing
      eggs in the shell have been developed. At least four research groups are
      attempting to devise a process to achieve a pasteurized shell egg. Only one of
      the groups has reported procedures and results. Sound shell eggs were washed to
      remove surface contaminants. The clean eggs were then inoculated with high levels
      of SE cells. The inoculated eggs were then heated by one of several means to a
      yolk temperature of about 55 C and held at that temperature for varying periods
      of time. The number of surviving cells was determined. It is possible to obtain a
      7 log cycle reduction of SE in inoculated eggs without a significant change in
      functional or visual quality of the eggs.

PMID- 8878273
TI  - Thermal and biological treatments to control psychrotrophic pathogens.
AB  - Over the past decade, advances in egg processing technologies have permitted
      commercial production of ultrapasteurized liquid whole egg (LWE) products with a
      shelf-life of greater than 10 wk at 4 C. The inactivation and control of
      psychrotrophic pathogens such as Listeria monocytogenes and Aeromonas hydrophila
      in extended shelf-life LWE and conventionally pasteurized egg products is an
      ongoing food safety concern. This manuscript reports on the common features of
      these two psychrotrophic pathogens, their incidence in egg products, and their
      survival, growth potential, and heat resistance in liquid egg. Furthermore, this
      manuscript reports in detail on the results of two specific studies conducted in
      our laboratory whose objectives were: 1) to determine the heat resistance (D
      values) of A. hydrophila in LWE using a low-volume immersed sealed glass
      capillary tube (ISCT) procedure; 2) to assess the impact of methodology (i.e.,
      ISCT procedure vs a conventional capped test tube procedure) on the apparent
      thermal resistance of A. hydrophila; and 3) to report on the use of the
      bacteriocin nisin to restrict the survival of L. monocytogenes in
      ultrapasteurized LWE stored at refrigeration temperatures.

PMID- 8878274
TI  - Pulsed light and pulsed electric field for foods and eggs.
AB  - Two new technologies for use in the food industry are described. The first method
      discussed uses intense pulse of light. This pulsed light (PureBright) process
      uses short duration flashes of broad spectrum "white" light to kill all exposed
      microorganisms, including vegetative bacteria, microbial and fungal spores,
      viruses, and protozoan oocysts. Each pulse, or flash, of light lasts only a few
      hundred millionths of a second (i.e., a few hundred microseconds). The intensity
      of each flash of light is about 20,000 times the intensity of sunlight at the
      earth's surface. The flashes are typically applied at a rate of about one to tens
      of flashes per second. For most applications, a few flashes applied in a fraction
      of a second provide an effective treatment. High microbial kill can be achieved,
      for example, on the surfaces of packaging materials, on packaging and processing
      equipment, foods, and medical devices as well as on many other surfaces. In
      addition, some bulk materials such as water and air that allow penetration of the
      light can be sterilized. The results of tests to measure the effects of pulsed
      light on Salmonella enteritiditis on eggs are presented. The second method
      discussed uses multiple, short duration, high intensity electric field pulses to
      kill vegetative microorganisms in pumpable products. This pulsed electric field
      (or CoolPure) process can be applied at modest temperatures at which no
      appreciable thermal damage occurs and the original taste, color, texture, and
      functionality of products can be retained.

PMID- 8878275
TI  - Innovative methods of energy transfer.
AB  - Energy is utilized in many forms for processing egg products and other foods.
      Energy in the form of heat has commonly been used to kill microorganisms and
      pasteurize eggs. Transfer of energy by convection and conduction is limited by
      the properties of the egg product. Energy transfer by radiation is being used to
      advantage in the development of innovative methods to kill or inactivate
      microorganisms. A review of the electromagnetic spectrum reveals underutilized
      forms of energy with unique properties. Specific frequencies and method of
      application are selected for their ability to focus energy toward the destruction
      of microorganisms and the production of safe food products for the public.

PMID- 8878276
TI  - Maternal serum screening and trisomy 16 confined to the placenta.
AB  - Five cases of trisomy 16 confined to the placenta have been detected by invasive
      procedures (amniocentesis and chorionic villus sampling) after high-risk results
      for Down syndrome and neural tube defects in a maternal serum screening programme
      of 6614 consecutive cases. All five pregnancies displayed unusually elevated
      levels of human chorionic gonadotropin and four out of five also had raised alpha
      fetoprotein values. No structural malformation was present but all five
      pregnancies were complicated by fetal growth retardation, and one by intrauterine
      death. From our results, we suggest that both amniocentesis and chorionic villus
      sampling should be considered in the management of cases with high mid-trimester
      levels of these analytes.

PMID- 8878277
TI  - Effect of allowing for ethnic group in prenatal screening for Down's syndrome.
AB  - We conducted a study to investigate ethnic group differences in levels of serum
      markers used in screening for Down's syndrome [serum alpha-fetoprotein (AFP),
      unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free
      alpha- and free beta-hCG, and dimeric inhibin-A], to estimate the extent to which
      maternal weight differences between ethnic groups explain these differences, and
      to estimate the effect of adjusting for ethnic group and maternal weight on
      screening performance. Serum measurements were taken from women who were screened
      prenatally for Down's syndrome. AFP, uE3, and hCG concentrations were available
      from 9462 white, 4215 black, and 4392 South Asian women with singleton
      pregnancies without Down's syndrome or neural tube defects between 15 and 22
      weeks' gestational age. Frozen serum samples were available from a subset of 922
      white, 449 black, and 135 South Asian women and were used for measurement of free
      alpha-hCG, free beta-hCG, and inhibin. Values were expressed as multiples of the
      median (MOM) for women of the same gestational age. There were statistically
      significant differences in the serum marker levels between ethnic groups that
      were not explained by differences in maternal weight. The main differences were
      found in black women compared with white women; black women had serum AFP levels
      22 per cent higher (95 per cent confidence interval 20-24 per cent), total hCG
      levels 19 per cent higher (16-22 per cent), and free beta-hCG levels 12 per cent
      (3-21 per cent) higher. The other differences were less than 10 per cent.
      Adjusting for ethnic group only had a small estimated effect on screening
      performance: a maximum of about 0.5 per cent extra detection at a 5 per cent
      false-positive rate. At a fixed risk cut-off level, the false-positive rate will
      not be materially different between different ethnic groups. Adjusting serum
      markers for ethnic groups improves Down's syndrome screening performance to a
      very small extent. It is worthwhile because of its established value in AFP
      screening for open neural tube defects.

PMID- 8878278
TI  - Serum markers for Down's syndrome in relation to number of previous births and
      maternal age.
AB  - We conducted a study to investigate the effect of parity on the following six
      serum markers used in screening for Down's syndrome, after adjusting them for
      ethnic group and maternal weight: alpha-fetoprotein (AFP), unconjugated oestriol
      (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG,
      and dimeric inhibin A. We aimed to estimate the effect of adjusting for any
      differences found on the screening performance. AFP, uE3, and hCG concentrations
      were available from 16,666 women with singleton pregnancies without Down's
      syndrome or neural tube defects and without insulin-dependent diabetes mellitus,
      who were screened between 15 and 22 weeks' gestational age. Stored serum samples
      were available on a subset of 1347 women and these were used to measure free
      alpha-hCG, free beta-hCG, and inhibin A. Serum concentrations were expressed as
      multiples of the median (MOM) for women of the same gestational age, weight, and
      ethnic group. Of the six markers, only hCG levels were affected by parity; hCG
      levels decreased by 3.1 per cent per previous birth (95 per cent confidence
      interval 2.2-4.0 per cent); there was no significant relationship between the
      number of previous abortions and hCG level after adjustment for the number of
      previous births. The effect of previous births on hCG was not due to maternal
      age. Only AFP was affected by maternal age, but the effect was small; levels
      increased by 4.4 per cent per 10 years of age (3.2-5.7 per cent). It is not
      worthwhile adjusting serum markers for parity or for maternal age in prenatal
      screening for Down's syndrome because their effect on the performance of
      screening is negligible.

PMID- 8878279
TI  - The outcome of pregnancies with confined placental chromosome mosaicism in
      cytotrophoblast cells.
AB  - Cytogenetic findings and outcome of pregnancy are reported in 108 cases in which
      confined placental mosaicism (CPM, n = 101) or generalized mosaicism (n = 7) was
      found at or after first-trimester chorionic villus sampling. In all samples, a
      (semi)direct cytogenetic analysis of cytotrophoblast cells was performed. Two
      pregnancies with CPM ended in a spontaneous abortion before 28 weeks (1.9 per
      cent). In 15 cases the pregnancy was terminated: eight cases were shown to be
      examples of CPM; seven cases can be considered as examples of generalized
      mosaicism. A normal cytogenetic result was obtained after follow-up amniocentesis
      in 88 of the remaining 91 cases. In three cases, no amniocentesis was performed
      but confirmation of a normal karyotype was obtained in other cells. One of the 91
      pregnancies was nevertheless terminated for psychosocial reasons. One child died
      perinatally and another on the seventh day after birth. The birth weight is known
      for 89 children; the curve shows a normal distribution. In 11 of these children
      (12.3 per cent), the birth weight was found to be below the tenth centile. The
      outcome in a subgroup of eight pregnancies with CPM and involvement of chromosome
      13, 16, or 22, however, revealed two fetal losses and four children with a birth
      weight below the tenth centile (75 per cent).

PMID- 8878280
TI  - Triple marker screening in native Japanese women.
AB  - Prenatal screening using the maternal serum markers alpha-fetoprotein, human
      chorionic gonadotropin, and unconjugated oestriol was investigated in a native
      Japanese population. Comparison with a Caucasian U.S. population revealed
      differences which led to modification of the generally used equations for risk
      calculations. Prenatal screening was shown to be clinically useful.

PMID- 8878281
TI  - Blood transfusion for haemolytic disease as a cause of leukocytosis in the fetus.
AB  - We evaluated the effect of fetal intravascular transfusion (IVT) of leukocyte
      poor red blood cells to correct fetal anaemia due to haemolytic disease on the
      fetal leukocyte count in 153 patients. Initial, mid-transfusion, and closing
      haematological studies were obtained when possible. The effect on leukocyte
      subsets was evaluated by the manual differential count. Fetal leukocyte count
      increased an average of 18.0 per cent during all IVTs (P < 0.01), despite the
      dilutional effect of the transfusion. The degree of leukocytosis increased with
      subsequent transfusions. The smallest (10.1 per cent) change occurred during the
      initial transfusion. A 41.8 per cent increase was noted during the sixth
      procedure. There was no relation between leukocytosis and gestational age, volume
      of transfusion, changes in umbilical vein pressure, or hydrops. Forty-two per
      cent of the increase was due to expansion of the neutrophil pool and 22 per cent
      was due to expansion of the monocyte pool. The neutrophil count increased 29 per
      cent (P < 0.01) and monocytes increased 64.7 per cent (P < 0.001). There was no
      change in eosinophil and lymphocyte counts. Both an immune aetiology and an
      effect of inflammatory agents may contribute to this leukocytosis.

PMID- 8878282
TI  - Second-trimester maternal serum alpha-fetoprotein, human chorionic gonadotropin,
      and unconjugated oestriol after early transvaginal multifetal pregnancy
      reduction.
AB  - Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and
      unconjugated oestriol (UE3) are used as second-trimester screening markers for
      the detection of various fetal abnormalities. Previous studies have suggested
      that second-trimester MSAFP is consistently elevated after late first-trimester
      transabdominal multifetal pregnancy reduction (MFPR). The present study was
      undertaken to evaluate the levels of all three markers after early transvaginal
      MFPR. Maternal serum was examined for MSAFP, hCG, and UE3 at 16-18 weeks'
      gestation in 28 patients who underwent transvaginal MFPR at approximately 10
      weeks' gestation. The mean interval between the reduction procedure and the
      screening test was 7.2 +/- 0.9 weeks. The mean MSAFP value in 24 patients
      carrying viable twins was 2.49 +/- 0.99 multiples of the median (MOM). Two
      patients had elevated MSAFP values: one in association with omphalocoele and the
      other in relation to an adverse pregnancy outcome. All but two patients had
      normal hCG values (mean 1.98 +/- 1.26 MOM). Two cases with elevated hCG were
      associated with an adverse pregnancy outcome. Unconjugated oestriol values were
      within the normal range in all patients (mean 1.69 +/- 0.61 MOM). These results
      suggest that early transvaginal MFPR, at approximately 10 weeks' gestation, does
      not appear to influence second-trimester MSAFP, hCG, and UE3 levels. The values
      of these markers may therefore be interpreted by using the same criteria as those
      for the general obstetric population.

PMID- 8878283
TI  - Glioependymal and arachnoid cysts: unusual causes of early ventriculomegaly in
      utero.
AB  - In this report we describe two cases of fetal midline intracranial cyst
      presenting with ventriculomegaly at routine detailed second-trimester scan. In
      the first case, additional findings included a banana-shaped hypoplastic
      cerebellum and macrocephaly; autopsy after termination of the pregnancy revealed
      a glioependymal cyst. In the second case, subsequent follow-up examination
      revealed a progressive increase in cyst size and worsening of ventriculomegaly;
      termination of pregnancy was performed at 24 weeks and autopsy confirmed an
      arachnoid cyst. These cases document interhemispheric cyst as a cause for early
      ventriculomegaly in utero.

PMID- 8878284
TI  - Trisomy 12/monosomy X/normal female mosaicism: prenatal detection and
      confirmation in a liveborn.
AB  - We report a case of mosaicism for three cell lines: 45,X, 46,XX, and 47,XX, + 12,
      diagnosed prenatally by amniocentesis done for advanced maternal age. Cord blood
      from the baby showed mosaicism for 45,X and 46,XX; cultures derived from multiple
      placental sites, villi, cord, membrane, and skin had varying proportions of all
      three cell lines. The patient at 18 months of age has mild physical dysmorphisms,
      hypotonia, delay in gross motor development, and age-appropriate cognitive
      development. The literature reveals variable outcomes for individuals with either
      mosaic trisomy 12 or mosaic Turner syndrome. Parental origin of the chromosome
      involved in a proposed corrected trisomy and/or the percentage of cell types in
      affected organs might account for the variability in outcomes seen.

PMID- 8878285
TI  - Partial trisomy/monosomy 6q in fetal cells and CVS long-term culture not present
      in CVS short-term culture.
AB  - A cytogenetic discrepancy in chorionic villi with implications for prenatal
      diagnosis is described. Chromosome analysis revealed a normal karyotype in banded
      metaphases from short-term culture and a chromosome count of 46 in cells of the
      long-term culture. After the birth of a malformed infant, a structurally aberrant
      chromosome 6 was found in lymphocytes and skin fibroblasts. Re-analysis of
      chorionic villi confirmed the result from short-term culture but disclosed the
      presence of the structural aberration in cells of the long-term culture. This
      type of inconsistency is reported for the first time and stresses the importance
      of a numerical and structural analysis of both short-term and long-term culture.
      The application of three techniques, chromosome banding, comparative genomic
      hybridization (CGH), and fluorescence in situ hybridization (FISH) analysis, was
      essential to prove that the derivative chromosome carried a combined partial
      trisomy/monosomy for 6q. The findings are discussed with respect to the origin of
      the structural aberration and to the consequences for prenatal diagnosis on
      chorionic villi and genetic counselling.

PMID- 8878286
TI  - Trisomy 16 mosaicism in amniotic fluid cell cultures.
AB  - Trisomy 16 mosaicism was found in amniotic fluid cells in a patient undergoing
      amniocentesis because of elevated second-trimester maternal serum alpha
      fetoprotein (MSAFP) (2.80 MOM), a markedly elevated human chorionic gonadotropin
      level (hCG) (12.02 MOM), and a Down syndrome risk of 1:55. Ultrasound evaluation
      of the fetus indicated the presence of an atrial septal defect and clinodactyly.
      Cytogenetic analyses of various fetal tissues using fluorescence in situ
      hybridization (FISH) failed to detect substantial numbers of trisomy 16 cells;
      however, trisomy 16 mosaicism was identified in placental tissue. Molecular
      genetic analysis at five different loci [four analysed by polymerase chain
      reaction (PCR) and one by Southern blot analysis] failed to show any evidence for
      uniparental disomy. Although trisomy 16 cells could not be clearly demonstrated
      in the fetus, the presence of a clinically significant proportion of aneuploid
      cells early in development could not be excluded and it therefore cannot be
      assumed that a 'confined placental mosaicism' existed. The markedly elevated hCG
      and elevated MSAFP levels are consistent with abnormal placental function in
      trisomy 16 mosaicism. Serial ultrasound evaluation (to detect any late-onset
      growth retardation) and fetal echocardiography may be indicated for patients with
      extraordinarily high levels of hCG, especially if MSAFP is also elevated.

PMID- 8878287
TI  - Circulatory Doppler parameters in fetal hypoxaemia.
AB  - A 32-year-old pregnant woman (gravida 1, para 0) was delivered at 27 weeks of
      gestation by elective Caesarean section because of regular fetal heart rate (FHR)
      decelerations. Doppler ultrasound assessment of the middle cerebral artery (MCA)
      and the ductus venosus (DV) showed pathological results, whereas the umbilical
      artery waveforms were normal. Blood gas analysis of the umbilical cord obtained
      at Caesarean section indicated fetal hypoxaemia. The discrepancy between abnormal
      Doppler findings in the central circulation and normal Doppler in the umbilical
      artery suggests that a detailed Doppler assessment may be necessary in order to
      clarify abnormal FHR tracings.

PMID- 8878288
TI  - Second-trimester ultrasonographic diagnosis of segmental vertebral abnormalities
      associated with neurological deficit: a possible new variant of occult spinal
      dysraphism.
AB  - Sonographic evaluation of the fetal spine in a second-trimester, low-risk patient
      revealed segmentary, low thoracic vertebral abnormalities, including hemi- and
      butterfly vertebrae, resulting in severe fetal scoliosis with fetal paraplegia
      and bilateral club-feet. X-ray and magnetic resonance imaging studies of the
      abortus confirmed the prenatal vertebral findings in addition to rib defects and
      transection of the spinal cord. We believe that these findings which, to the best
      of our knowledge, have not been previously reported, represent a new variant of
      occult spinal dysraphism.

PMID- 8878289
TI  - Ultrasound and molecular mid-trimester prenatal diagnosis of de novo
      achondroplasia.
AB  - In a low-risk pregnant patient at 21 weeks' gestation, ultrasound revealed
      shortening of fetal long bones compatible with achondroplasia. Funipuncture was
      performed and DNA analysis of fetal blood demonstrated the presence of the GR380R
      fibroblast growth factor receptor 3 (FGFR3), which is specifically associated
      with achondroplasia. After termination of the pregnancy, necropsy confirmed the
      prenatal diagnosis. A certain sonographic diagnosis of fetal de novo
      achondroplasia is rarely possible prior to viability. The specificity of the
      FGFR3 causative mutation has added a new diagnostic option which can be applied
      prenatally for diagnostic validation.

PMID- 8878290
TI  - Re: Cross-hybridization of the chromosome 13/21 alpha satellite DNA probe to
      chromosome 22 in the prenatal screening of common aneuploidies by FISH.

PMID- 8878291
TI  - Roberts syndrome: first-trimester prenatal diagnosis.

PMID- 8878293
TI  - Current awareness in prenatal diagnosis.

PMID- 8878292
TI  - Prenatal detection of chromosome 20 variants (20ph+, 20ps)

PMID- 8878294
TI  - ST segment deviation during myocardial ischemia: are there gender differences?
AB  - Prior research indicates that women have greater ST segment shifts at the time of
      percutaneous transluminal coronary angioplasty (PTCA) balloon inflation than men.
      However, ST deviation in men and women has not been compared during balloon
      occlusion of the same coronary vessel. METHODS: To determine whether there is a
      gender difference in degree of ST deviation, 12-lead electrocardiographic (ECG)
      recordings were made in 45 subjects undergoing PTCA (25 men, 20 women). A total
      ST score was obtained by summing absolute deviations across all 12 leads. All
      patients had single vessel coronary artery lesions in the proximal half of one of
      the major epicardial arteries without evidence of collateral circulation.
      RESULTS: There were no differences between men and women in terms of age, left
      ventricular hypertrophy, ejection fraction, or the Norris Coronary Prognostic
      Index, which combines age, history of infarction, and evidence of heart failure
      on chest X-ray. When comparing mean ST segment deviation in men and women, vessel
      to vessel, no gender differences were found. CONCLUSION: When matched for
      coronary vessel, men and women have comparable ST deviation patterns during
      coronary occlusion with PTCA balloon inflation. Therefore, detection of
      myocardial ischemia related to coronary occlusion with continuous ST segment
      monitoring should be equally sensitive in men and women.

PMID- 8878295
TI  - Parental understanding of the consequences of pediatric cardiac transplantation.
AB  - Pediatric cardiac transplantation has profound medical, social, psychological and
      economic consequences. Parents need to understand both the medical and non
      medical consequences of the transplant procedure to make a judicious decision
      about this treatment. The purpose of this study was to determine the parental
      understanding of the multiple consequences of transplantation. A prospective
      ethnographic method was used to study 24 parents of 15 children prior to their
      decision to accept or reject the transplant option for their children. Findings
      revealed that the medical consequences of transplantation were well addressed by
      the pediatric cardiac transplant team. Little attention, however, was given to
      the non-medical concerns of the parents. The importance of nursing interventions
      related to information clarification and support for parents as they make
      decisions about heart transplantation for their children was identified.

PMID- 8878296
TI  - Assessment and intervention for ischemic chest pain: a case study with legal
      implications for nursing practice.
AB  - In order to reduce early and long-term mortality and morbidity from myocardial
      infarction, nurses must promptly and thoroughly assess chest pain, intervene
      quickly and evaluate the results of the interventions. In Kielley v. General
      Hospital Corp. et al, a patient suffered a massive heart attack while under
      observation on a cardiology unit. The court held the hospital liable for the
      nurses' breach of its chest pain protocol and for failing to have
      electrocardiograms done when the patient experienced pain. The case clearly
      illustrates the harm a patient may incur when nurses fail to properly assess and
      intervene. It reinforces the importance of adherence to hospital protocols that
      have been put in place to ensure patient safety.

PMID- 8878297
TI  - Cardiovascular clinical nurse specialists: demographic, practice and educational
      characteristics.
AB  - In 1993, California mandated a study of the practice characteristics of Clinical
      Nurse Specialists (CNSs) in the state. This report describes, compares and
      contrasts the demographic, practice and educational characteristics of a
      subsample of cardiovascular CNSs with the rest of the CNS sample. Cardiovascular
      CNSs tended to have characteristics more indicative of a hospital-based specialty
      and the role appeared to be more consistently established than the general CNS
      sample. In addition, cardiovascular CNSs had a significantly higher percentage of
      graduate-prepared nurses. They had significantly fewer interactions in
      outpatient, community, and home settings than the rest of the CNS group. While
      cardiovascular CNSs play a vital role in the high technology-based hospital
      setting, they do not appear to be moving out of that setting as are other CNSs.
      This is an interesting finding since cardiovascular disease is chronic and well
      suited to outpatient management within the CNS charter. These findings may aid in
      establishing future opportunities for cardiovascular CNSs in the new health care
      environment, as well as serve as a benchmark for educators of CNSs.

PMID- 8878298
TI  - Antiarrhythmic drug therapy--Part II: Specific drugs.

PMID- 8878299
TI  - Can ambulatory ECG monitoring serve as an effective marker in identifying severe,
      active coronary disease in patients with silent ischemia?

PMID- 8878300
TI  - Refusing to pay for health care--Part III (of III): Avoiding third-party payer
      liability.

PMID- 8878301
TI  - Port-access coronary artery bypass graft (CABG): an emerging approach to
      revascularization.

PMID- 8878302
TI  - "Relative" sinus bradycardia.

PMID- 8878303
TI  - Glia-neuron intercommunications and synaptic plasticity.
AB  - It is established that astrocytes are the intimate partner of neurons throughout
      their lifespan. However, astrocytes play different roles at different stages of
      the lifespan. During neurogenesis and early development, glial cells provide a
      scaffold for the correct migration of neurons and growth cones. They provide
      guidance cues and may also be involved in neuronal proliferation. In the adult,
      astrocytes maintain neuronal homeostasis and synaptic plasticity. This review
      discusses some of the cell-cell communication signals which are involved in the
      maintenance of synaptic plasticity. They are divided into: (a) glia-to-glia
      signaling, which involves non-synaptic communication by coupling of astrocytes.
      In this cell communication, cytoplasmic exchange of ions and small molecules
      among cells is accomplished through cell coupling of cells via cell-to-cell
      contacts, termed gap junctions; (b) neuron-to-glia signaling, which involves
      synaptic interactions. This cell-cell intercommunication has received
      considerable attention. Of special interest is the role of astrocytes in glutamic
      acid compartmentation and in preventing glutamic acid neurotoxicity. A glutamate
      induced calcium signaling appears to be involved in this neuron-astrocyte
      interaction. The intriguing possibility is that neuronally induced astrocyte
      calcium signals may feed back to influence neuronal excitability or regulate
      synaptic transmission; (c) signals from astrocytes to neurons: a new concept of
      neuron-glia intercommunication. As mentioned, calcium appears to be the molecule
      in this glia-neuron signaling, although glial cell receptor-mediated signals are
      involved also. Receptor interactions on astrocytes through a cascade of events
      lead to modification in the extracellular concentration of glutamate. The role of
      astrocytes in synaptic plasticity is not as well understood during ageing and
      their role in neuronal cell death during ageing and neurodegeneration can only be
      speculated. However, astrocytes in the aged brain exhibit various receptors,
      including glutamate receptors. Thus, astrocytes can be expected to modify the
      expression of endogenous neurotoxins and thus contribute to synaptic plasticity
      in ageing. Synaptic plasticity continues to be a homeostatic relationship between
      neurons and glial cells. The possibility of signaling from astrocytes to neurons
      has opened new horizons for glial cell function and new challenges of research
      for gliobiologists.

PMID- 8878304
TI  - Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their
      physiological sequelae.
AB  - One of the primary approaches in experimental brain research is to investigate
      the effects of specific destruction of its parts. Here, several neurotoxins are
      available which can be used to eliminate neurons of a certain neurochemical type
      or family. With respect to the study of dopamine neurons in the brain, especially
      within the basal ganglia, the neurotoxin 6-hydroxydopamine (6-OHDA) provides an
      important tool. The most common version of lesion induced with this toxin is the
      unilateral lesion placed in the area of mesencephalic dopamine somata or their
      ascending fibers, which leads to a lateralized loss of striatal dopamine. This
      approach has contributed to neuroscientific knowledge at the basic and clinical
      levels, since it has been used to clarify the neuroanatomy, neurochemistry, and
      electrophysiology of mesencephalic dopamine neurons and their relationships with
      the basal ganglia. Furthermore, unilateral 6-OHDA lesions have been used to
      investigate the role of these dopamine neurons with respect to behavior, and to
      examine the brain's capacity to recover from or compensate for specific
      neurochemical depletions. Finally, in clinically-oriented research, the lesion
      has been used to model aspects of Parkinson's disease, a human neurodegenerative
      disease which is neuronally characterized by a severe loss of the meso-striatal
      dopamine neurons. In the present review, which is the first of two, the lesion's
      effects on physiological parameters are being dealt with, including histological
      manifestations, effects on dopaminergic measures, other neurotransmitters (e.g.
      GABA, acetylcholine, glutamate), neuromodulators (e.g. neuropeptides,
      neurotrophins), electrophysiological activity, and measures of energy
      consumption. The findings are being discussed especially in relation to time
      after lesion and in relation to lesion severeness, that is, the differential role
      of total versus partial depletions of dopamine and the possible mechanisms of
      compensation. Finally, the advantages and possible drawbacks of such a
      lateralized lesion model are discussed.

PMID- 8878305
TI  - Encoding of tooth loads by human periodontal afferents and their role in jaw
      motor control.
AB  - Microneurography has been used to analyze the functional properties of human
      periodontal mechanoreceptors. Signals were recorded from single afferents in the
      inferior alveolar nerve while controlled forces were applied to the teeth. We
      have found that all periodontal afferents adapt slowly to maintained loads. Most
      afferents are tuned broadly to direction of force application, and about half
      respond to forces applied to teeth adjacent to the one to which the afferent
      distributes. Populations of periodontal afferents, nevertheless, reliably encode
      information about both the teeth stimulated and the direction of forces applied
      to the individual teeth. Information about the magnitude of steady forces is made
      available in the mean firing-rate response of periodontal afferents. Most
      afferents exhibit a marked "hyperbolic" relationship between the static discharge
      rate and the force amplitude; the highest sensitivity to changes in static force
      is observed at forces below 1 N. Similarly, the dynamic sensitivity is highest at
      low forces. These afferents efficiently encode food contact during biting and
      continuously discharge while food is held between the incisors. Subjects
      spontaneously exert low contact forces matched to the sensitivity characteristics
      of these periodontal afferents when holding food substances between the incisors.
      If periodontal afferent information is not available, the control of the hold
      forces is severely impaired. Moreover, since only a few afferents encode
      information about the rapid and strong force increase employed to bite through
      food, we conclude that subjects rely on signals from periodontal afferents to
      regulate the jaw muscles primarily when they first contact, manipulate and hold
      food substances between the teeth. A potential role for periodontal afferents in
      the spatio-intensive control of jaw actions is discussed.

PMID- 8878306
TI  - Plasma monoamine metabolites and spontaneous recurrence of methamphetamine
      induced paranoid-hallucinatory psychosis: relation of noradrenergic activity to
      the occurrence of flashbacks.
AB  - The relationship between monoamine neurotransmitter function and spontaneous
      recurrence of methamphetamine (MAP) psychosis, a phenomenon known as flashbacks,
      was studied in a group of incarcerated women. Plasma levels of norepinephrine
      (NE), dopamine, 5-hydroxytryptamine, and their respective metabolites were
      assayed in 28 flashbackers, 19 non-flashbackers with a history of previous MAP
      psychosis, and 9 subjects with persistent MAP psychosis. Control data were
      available from 61 physically healthy prisoners (41 MAP users and 20 non-users,
      none of whom became psychotic). The plasma NE levels of the 28 flashbackers
      during flashbacks were significantly higher than levels during periods of
      normality, and were significantly higher than those in the MAP user and non-user
      controls. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels during flashbacks
      were significantly higher than those in the user controls. The nine subjects with
      persistent MAP psychosis had significantly higher NE levels than the user and non
      user controls. The 19 non-flashbackers had significantly higher MHPG levels than
      the user controls. Plasma levels of 3-methoxytyramine and dihydroxyphenylacetic
      acid contributed to the NE levels in the flashbackers, in contrast to the
      findings in the control group. Noradrenergic systems may be compromised in the
      flashbackers, suggesting increased vulnerability to psychotic decompensation.
      These findings suggest that aggravation in peripheral noradrenergic hyperactivity
      may be an important factor in the occurrence of flashbacks.

PMID- 8878307
TI  - Impairment of the semantic network in schizophrenia.
AB  - It is well established that patients with schizophrenia display a variety of
      language impairments. Despite considerable research, however, the underlying
      mechanisms of the language deficits in schizophrenia remain unclear.
      Representations of semantic networks of 56 patients with schizophrenia and 28
      normal comparison (NC) subjects of similar ages and educational levels were
      generated by multidimensional scaling and Pathfinder analyses of their responses
      on the Animal Fluency Test. On the basis of traditional scoring techniques (i.e.,
      total number of correct animal names generated in 60 s), all patients performed
      significantly worse than the NC subjects. More detailed analyses of the
      underlying semantic networks revealed that performance in the patients varied
      according to age of onset and subtype of schizophrenia. The semantic network of
      patients with late-onset schizophrenia (i.e., with onset after age 45) was
      virtually identical to that of the NC group. In contrast, the semantic network of
      patients with a younger age of onset was disorganized and differed significantly
      from that of the NC subjects. Findings demonstrated that patients with
      nonparanoid subtypes displayed greater disorganization in their semantic networks
      than patients with a paranoid subtype. Although general fluency impairments
      (e.g., difficulties in initiation, retrieval, and search mechanisms) may be
      sensitive to schizophrenia, per se, specific deficits in the structure of
      semantic knowledge may be associated with certain characteristics of individual
      patients with schizophrenia, such as an earlier age of onset and nonparanoid
      subtype.

PMID- 8878308
TI  - Decreased serotonergic responsivity in platelets of drug-free patients with
      schizophrenia.
AB  - We have recently developed a simplified and time-saving method to measure the
      magnitude of serotonin (5-hydroxytryptamine, 5HT)-amplified platelet aggregation
      and dense granule secretion (DGS) responses. To study the effects of neuroleptics
      on peripheral serotonergic function, we measured physiologic responsivity of the
      platelet 5HT2 receptor complex in schizophrenic patients (n = 27), both before
      and after haloperidol withdrawal, and also in normal volunteers (n = 18). In
      human platelets, 5HT amplifies the adenosine diphosphate (ADP)-induced platelet
      aggregation and DGS. Such an amplification was significantly enhanced in
      platelets from both normal volunteers and haloperidol-stabilized patients.
      Following haloperidol withdrawal, however, the magnitude of 5HT-amplified DGS
      response was no longer significant in drug-free patients, demonstrating a
      decreased serotonergic responsivity in schizophrenia. Moreover, in drug-free
      patients, the net changes of ADP-induced DGS, with and without the presence of
      5HT, were correlated significantly and negatively with both Bunney-Hamburg
      psychosis ratings and Brief Psychiatric Rating Scale (total) scores, but not with
      scores on the Scale for the Assessment of Negative Symptoms. In the drug-free
      group, no significant difference of 5HT amplification was demonstrated between
      relapsed and nonrelapsed patients. The present finding thus suggests that drug
      free schizophrenic patients may have a reduced physiologic responsivity mediated
      through the platelet 5HT2 receptor complex, which can be modified by haloperidol
      treatment. The pharmacologic action of haloperidol may derive in part from
      serotonergic mechanisms. The magnitude of 5HT-amplified DGS may be useful in the
      prediction of therapeutic outcome after haloperidol treatment.

PMID- 8878309
TI  - Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts
      from schizophrenic patients: comparison with bipolar patients and normal
      subjects.
AB  - Recent studies have found lower red cell plasma membrane contents and composition
      of the long chain polyunsaturated essential fatty acid derivatives, particularly
      arachidonic acid and docosahexaenoic acid, in a subgroup of chronic schizophrenic
      patients. These fatty acids are particularly enriched in the brain. Red blood
      cell levels of fatty acids are influenced by diet, medications, and other
      factors. Cell plasma membrane compositions of arachidonic and docosahexaenoic
      acids were therefore examined in cultured skin fibroblasts from 12 schizophrenic
      patients, 8 of whom were drug-naive and in a first episode of psychosis, 6
      bipolar patients, and 8 normal control subjects. Docosahexaenoic acid as well as
      total n-3 essential fatty acid contents were significantly lower in cell lines
      from schizophrenic patients than in cell lines from bipolar patients and normal
      subjects, with no difference between the latter two groups. Arachidonic acid
      levels did not differ across the groups. The essential fatty acid profile
      observed is consistent with deficient delta-4 desaturase activity in
      schizophrenic patients.

PMID- 8878310
TI  - Platelet imipramine binding in patients with posttraumatic stress disorder before
      and after phenelzine treatment.
AB  - Posttraumatic stress disorder (PTSD) is frequently associated with major
      depressive disorder, and antidepressants have been reported to ameliorate PTSD
      symptoms in some patients. The present study assessed the number and affinity of
      platelet imipramine binding sites, as a marker of the serotonin transporter
      complex, in PTSD male patients (n = 10) before and after phenelzine treatment (30
      60 mg/day, for 4 weeks) as well as in comparison to healthy controls (n = 10). In
      our sample, there was no evidence of a significant difference in the
      characteristics (Bmax and Kd) of platelet [3H]imipramine binding between the PTSD
      patients and the controls and within PTSD patients before and after phenelzine
      treatment. Moreover, no beneficial effect of phenelzine was detected in the
      patients (as assessed by PTSD, anxiety, and depression scales).

PMID- 8878311
TI  - Red blood cell L-tryptophan uptake in depression: kinetic analysis in untreated
      depressed patients and healthy volunteers.
AB  - Kinetic parameters (Vmax and K(m)) of L-tryptophan (TRP) uptake into red blood
      cells (RBC) were measured in 72 drug-free depressed inpatients and 35 healthy
      volunteers. Mean Vmax and K(m) values were not significantly different between
      patients and volunteers. The frequency distributions of Vmax values, however,
      largely differed in the two groups: Vmax values were homogeneous in the
      volunteers while they were widely scattered in the depressed patients. Only 15
      out of the 72 depressed patients (21%) had Vmax values within 1 SD from the mean
      control value. Forty-four percent of the patients (n = 32) had Vmax values above
      the control mean + 1 SD in 11 patients and above the control mean + 2 SD in 21
      patients. Thirty-five depressed patients (n = 25) had Vmax values below the
      control mean - 1 SD in 8 patients and below the control mean - 2 SD in 17
      patients. High and low K(m) values were observed in combination with high and low
      Vmax values. The alterations in kinetic parameters were neither associated with
      severity of depression nor with a specific diagnostic subtype of depression. The
      data show abnormalities in RBC L-TRP uptake in most depressed patients that
      likely reflect a disturbance in peripheral availability of TRP on which central
      serotonin synthesis closely depends.

PMID- 8878312
TI  - Relationship between sleep and mood in patients with rapid-cycling bipolar
      disorder.
AB  - The relationship between sleep and mood was examined in a longitudinal,
      naturalistic data set derived from out-patients with rapid-cycling bipolar
      disorder. Eleven patients completed daily self-ratings of mood and sleep logs for
      18 months. Using logistic regression with autoregressive terms, we examined the
      effect of prior sleep (sleep duration, time of sleep onset, and time of wake
      onset) on the probability of being in a depressed, manic, or hypomanic episode on
      one or more subsequent days. Of the three sleep parameters, decreased sleep
      duration was the best predictor of mania or hypomania the next day, followed by
      wake onset time. The association between sleep duration and subsequent mood was
      less consistent for depression than for mania or hypomania. Four of the patients
      showed no relationship between mood and any of the sleep variables measured.
      These results reinforce the importance of monitoring, and perhaps controlling,
      sleep duration and wake onset time in at least some patients with rapid-cycling
      bipolar disorder.

PMID- 8878313
TI  - Quality of well-being in late-life psychosis.
AB  - Research in mental health has generally used evaluation and outcome measures
      different from those applied in other medical specialties. We evaluated the
      utility of a general health measure, the Quality of Well-Being (QWB) scale, in
      older patients with psychosis. The QWB and standardized rating scales for
      assessing psychopathology, cognitive impairment, physical comorbidity, and
      neuroleptic-induced tardive dyskinesia were administered to 85 patients with
      functional psychoses (mostly schizophrenia or schizoaffective disorder) and 39
      normal comparison subjects over age 45. The patients were more impaired than
      normal comparison subjects on the QWB and other rating scales. The QWB score was
      affected more by severity of positive symptoms than by any non-psychopathology
      related variables. The patients' QWB scores were similar to those of previously
      studied ambulatory patients with AIDS. Use of the QWB scale may allow direct
      comparisons of the impact of different psychiatric and physical disorders on the
      quality of life.

PMID- 8878314
TI  - Quality of life in elderly patients with recurrent major depression: a factor
      analysis of the General Life Functioning Scale.
AB  - Quality of life profiles measured by the General Life Functioning (GLF) Scale
      were examined in elderly patients with recurrent major depression, before and
      during combined treatment with nortriptyline and interpersonal psychotherapy. The
      study group included 110 patients, 91 recovered and 19 nonrecovered, aged 60 to
      80 years, suffering from at least their second lifetime episode of major
      depression. Repeated measures analysis of covariance (with Hamilton and Beck
      depression scores as time-dependent covariates) was used to compare the temporal
      course of overall GLF scores for the recovered and the nonrecovered groups.
      Factor analysis was used to examine whether the GLF Scale yielded an overall
      score and measured specific aspects of well-being and coping. There were
      significant differences in the overall GLF scores between recovered and
      nonrecovered patients, with the differences increasing from week 8 of treatment
      onward. Analysis revealed significant improvements in quality of life, as
      measured by overall GLF scores, over the course of treatment in both recovered
      and nonrecovered patients. Even when changes in Hamilton and Beck depression
      ratings were controlled for in the statistical analysis, improvements in GLF
      scores were found to be greater in recovered than in nonrecovered patients. Thus,
      the GLF measures more than change in level of depression. Its overall score also
      has high internal reliability.

PMID- 8878315
TI  - Long-term effects of antidepressants on balance, equilibrium, and postural
      reflexes.
AB  - To assess the long-term effects of antidepressant medication on balance,
      equilibrium, and postural reflexes, we studied 30 patients, ages 20-76 years, who
      had a diagnosis of depressive disorder (as defined by DSM-III-R criteria) and had
      been treated with tricyclic antidepressants (TCAs) or selective serotonin
      reuptake inhibitors (SSRIs) for > or = 1 year. They were assessed by a Balance
      Master System. The assessment included three tasks: static balance, rhythmic
      weight shift, and limits of stability. When compared with 30 nonhospitalized
      healthy controls (of comparable age and the same sex), patients who took TCAs
      showed impaired balance function in all main indices. The results suggest that
      the impairment of balance function includes motor coordination, fine-motor
      control, postural reflexes, maintaining equilibrium, and reaction time. No
      obvious impairment of balance function was observed in patients who took SSRIs.

PMID- 8878316
TI  - Modulation of learned helplessness by 5-hydroxytryptamine2A receptor antisense
      oligodeoxynucleotides.
AB  - Serotonergic systems have been implicated in the pathogenesis of major depression
      in humans as well as in learned helplessness (LH), an animal model of depression.
      To understand the significance of neuronal responses in depression and LH that
      are mediated by serotonin (5-hydroxytryptamine, 5HT) receptors, we used
      intracerebroventricular injections to introduce a unique antisense
      oligonucleotide (ASO) to the 5HT2A receptor and determined its effect on LH
      behavior in Sprague-Dawley rats as determined by an escape-avoidance strategy. Of
      the rats injected with the 5HT2A receptor ASO, 8/16 rats met criteria for LH. By
      contrast, only 1/15 of the control group injected with 5HT2A sense
      oligonucleotide (SO) met criteria for LH. Quantitative receptor autoradiography
      revealed significant differences in 5HT2A receptor density between ASO and
      control sense oligonucleotides (SO), in close proximity to the injection site.
      Significant decreases in 5HT2A receptor density caused by oligonucleotide
      blockade were found in the CA3 hippocampal region. These data support the view
      that central 5HT, mediated by the 5HT2A receptor, participates in regulating
      behaviors that are affected by inescapable stress, and that the induction of
      behavioral depression may be specifically regulated via serotonergic pathways
      that terminate in this hippocampal subfield.

PMID- 8878317
TI  - Psychometric characteristics of the Children's Motivation Scale.
AB  - A 16-item Children's Motivation Scale (CMS) was developed to evaluate level of
      motivation in children and adolescents. The study population consisted of a
      normative sample of 290 school children and a clinical sample of 165 child and
      adolescent psychiatric patients. Test-retest, internal consistency, and
      interrater reliability were fair to good for both samples. Validity of the CMS
      was demonstrated by its ability to differentiate clinical from normative samples
      according to the level of motivation, by a significant correlation of the CMS
      with an independent measure of withdrawal, and by its lack of correlation with an
      independent measure of depression. Principal components analysis identified a
      three-component structure. These findings support the conclusion that the CMS
      accesses a clinically important but often overlooked psychiatric construct.

PMID- 8878318
TI  - Nocturnal melatonin and 24-hour 6-sulphatoxymelatonin levels in various phases of
      bipolar affective disorder.
AB  - Nine bipolar patients (2 men and 7 women) and 12 healthy control subjects
      completed overnight sampling for serum melatonin (MT) and urinary 6
      sulphatoxymelatonin (aMT6s). The patients were investigated during manic,
      depressed, and/or euthymic states. Although serum MT levels did not differ
      significantly across the bipolar groups, in all cases serum MT levels were
      significantly lower than in control subjects. Differences in MT levels were also
      present between bipolar patients who were in a depressed phase and control
      subjects. There were no statistically significant differences in urinary aMT6s
      levels among the patients and control subjects, although in all cases nocturnal
      aMT6s levels were significantly higher than daytime levels. This study provides
      tentative evidence for decreased serum MT as a trait but not a state marker in
      bipolar affective disorder.

PMID- 8878319
TI  - Plasma levels of gamma-aminobutyric acid and panic disorder.
AB  - Low levels of gamma-aminobutyric acid (GABA) in plasma have been associated with
      the presence of mood disorders in patients with major depressive disorder. We
      examined plasma GABA in patients with panic disorder, a disorder that is often
      comorbid with major depression, and in a group of control subjects. Patients with
      panic disorder had plasma GABA levels that did not differ significantly from
      levels in controls subjects. These data support the specificity of low plasma
      GABA as a marker for mood disorders.

PMID- 8878320
TI  - Does minimizing neuroleptic dosage influence hyponatremia?
AB  - Neuroleptic dosage was reduced by 10% every 2 weeks in five male hyponatremic
      polydipsic patients with schizophrenia. Mean dose fell from 1980 +/- 1289 to 631
      +/- 135 chlorpromazine equivalents/day over a mean of 12.2 weeks until behavioral
      relapse occurred. During this time, serum sodium did not vary from baseline
      levels (132.9 +/- 4.9 mEq/1), suggesting that minimizing neuroleptic dose does
      not alter the severity of hyponatremia in these patients.

PMID- 8878321
TI  - Cataplexy and the switch process of multiple personality disorder.
AB  - A case history is presented of an 18-year-old male with dissociative disorder and
      polysubstance abuse. The patient was observed to switch between three
      personalities, and the personality changes were often associated with symptoms of
      cataplexy. Both dissociative episodes and cataplexy are associated with strong
      affective stimuli. Similar reports in the literature are briefly reviewed.

PMID- 8878322
TI  - What do we know about peer review?

PMID- 8878323
TI  - Poor and mad: a study of patients admitted to the Fife and Kinross District
      Asylum between 1874 and 1899.
AB  - This is the first detailed study of patients admitted to a Scottish pauper
      asylum. A one in four sample of patients admitted to the Fife and Kinross
      District Asylum between 1874 and 1899 was undertaken and yielded 262 males and
      266 females. Each patient's case-notes were studied from admission to the time of
      discharge and a wide range of information relating to sociodemographic and
      clinical features was extracted and subsequently analysed. The study found that
      while the Fife and Kinross Asylum shared many of the features of its English
      counterparts, the general picture was less bleak: the Asylum population did not
      grow to such large numbers; the recovery rate did not fall so precipitately and
      even rose towards the end of the century and cases of general paralysis were less
      frequent. In the discussion, these findings are related to other asylum studies.

PMID- 8878324
TI  - Homesickness: a review of the literature.
AB  - Homesickness has not received due attention from psychological researchers, in
      spite of the fact that it is of considerable interest to counsellors and care
      givers of those who have migrated or moved temporarily or permanently (e.g.
      immigrants, refugees, students, soldiers). First, this review addresses the
      definition of homesickness, the possible different kinds of homesickness, its
      prevalence rate, and symptomatology, Secondly, an overview is given of the
      theories that account for psychological distress following leaving home. These
      theories link homesickness with separation-anxiety and loss, the interruption of
      lifestyle, reduced control, role change, and internal conflict. In addition, the
      review focuses on: (i) studies that show that subjects reporting homesickness
      differ from non-homesick persons in terms of personality; (ii) the analyses of
      environmental characteristics that may play a crucial role in the onset and
      course of homesickness. Thirdly, Fisher's (1989) composite model of homesickness,
      which summarizes key findings of the major studies on homesickness is discussed.
      Fourthly, methodological issues are addressed. Finally, suggestions for future
      research are presented and possibilities for interventions are proposed.

PMID- 8878325
TI  - A savant poet.
AB  - Poems by an individual with a diagnosis of Asperger's Syndrome were analysed and
      compared with those of a comparison poet. Though the savant poet performed less
      efficiently on formal language tests supposed to tap creativity, there were few
      differences between the two poets in regard to the poems' content and the use of
      various structural devices. The poems by the savant referred more often to
      aspects of self-analysis, while descriptions of people not related to the self
      were less frequent. Both poets made use of similes and metaphors. The results are
      discussed in terms of different modular domains within the language system.

PMID- 8878326
TI  - Steroid hormones, the menopause, sexuality and well-being of women.
AB  - One hundred and forty-one women, aged 40-60 years, recruited from the community
      were assessed with an initial interview, plus four interviews at intervals of 1
      week and blood samples. The objective was to investigate the determinants of
      sexuality and well-being in this sample. Measures included interview ratings of
      sexual function, Frenken Sexual Experience Scales and the Multiple Affect
      Adjective Check List. Determinants evaluated, using multiple regression analysis,
      included age, menopausal status, BMI, smoking, ovarian steroids and adrenal
      androgens. None of the hormonal parameters significantly predicted measures of
      sexuality; the most important predictors were other aspects of the sexual
      relationship, sexual attitudes and measures of well-being. The best predictor of
      both well-being and depression was tiredness. The only hormone positively related
      to well-being was dehydroepiandrosterone (DHEA).

PMID- 8878327
TI  - Patients who somatize in primary care: a longitudinal study of cognitive and
      social characteristics.
AB  - We examined the cognitive and sociodemographic characteristics of patients making
      somatic presentations of depression and anxiety in primary care. Only 15% of
      patients with depressive symptomatology on self-report, and only 21% of patients
      with current major depression or anxiety disorders on diagnostic interview,
      presented psychosocial symptoms to their GP. The remainder of patients with
      psychiatric distress presented exclusively somatic symptoms and were divided into
      three groups-initial, facultative and true somatizers-based on their willingness
      to offer or endorse a psychosocial cause for their symptoms. Somatizers did not
      differ markedly from psychologizers in sociodemographic characteristics except
      for a greater proportion of men among the true somatizers. Compared to
      psychologizers, somatizers reported lower levels of psychological distress, less
      introspectiveness and less worry about having an emotional problem. Somatizers
      were also less likely to attribute common somatic symptoms to psychological
      causes and more likely to endorse normalizing causes. In the 12 months following
      their initial visit, somatizers made less use of speciality mental health care
      and were less likely to present emotional problems to their GP. Somatizers were
      markedly less likely to talk about personal problems to their GP and reported
      themselves less likely to seek help for anxiety or sadness. Somatization
      represents a persistent pattern of illness behaviour in which mental health care
      is not sought despite easily elicited evidence of emotional distress.
      Somatization is not, however, associated with higher levels of medical health
      care utilization than that found among patients with frank depression or anxiety.

PMID- 8878328
TI  - The Suffolk County Mental Health Project: demographic, pre-morbid and clinical
      correlates of 6-month outcome.
AB  - The diagnostic specificity and predictive utility of the classical prognostic
      indicators in schizophrenia were examined in psychotic patients enrolled in the
      Suffolk County Mental Health Project. First-admission psychotic patients with
      schizophrenia (N = 96), major depression (N = 42), and bipolar disorder (N = 64)
      drawn from 10 facilities in Suffolk County, New York, were assessed during their
      initial hospitalization and at 6-month follow-up. Longitudinal consensus
      diagnoses were determined after the 6-month interview. The diagnostic groups
      shared similar background characteristics, but schizophrenics had poorer pre
      morbid adjustment, longer periods of psychosis before hospitalization and more
      negative symptoms initially. Except for rehospitalization, schizophrenics had the
      worst and bipolars the best functioning at follow-up. Among the classical
      prognostic indicators, the best predictor of 6-month outcome for each diagnostic
      group was premorbid functioning.

PMID- 8878329
TI  - Age-period-cohort analysis of the incidence of schizophrenia in Scotland.
AB  - Studies examining a possible decline in the incidence of schizophrenia over the
      last two to three decades have paid little attention to the possible role of
      birth cohort effects. We collected data on a Scottish national sample of all
      schizophrenic patients, admitted for the first time between 1966 and 1990 (N =
      11348; male = 6301). In an Age-Period-Cohort analysis, a full model,
      incorporating three factors, had a substantially better fit to the data than
      other models (especially, an Age-Period model), providing clear evidence of the
      presence of a cohort effect. After adjustment for the effects of age and period,
      there was a 55% reduction in the rate of schizophrenia in men and a 39% fall in
      the number of women over the 50-year birth period from 1923 to 1973. The marked
      decline in the first admission rates observed in Scotland cannot, however, be
      attributed entirely to this cohort effect. Rather, a greater proportion of the
      declining first admission rates (88%) is ascribed to the period effect (i.e.
      artefactual or causally related cross-sectional effects). Nevertheless, the fact
      that a birth-cohort effect accounts for part of the declining incidence, suggests
      that causal environmental factors operating early in life have been diminishing
      in intensity.

PMID- 8878330
TI  - Neuropsychological impairments in unipolar depression: the influence of perceived
      failure on subsequent performance.
AB  - The CANTAB battery of neuropsychological tests was used to compare the
      performance of 28 patients with unipolar depression with that of 22 age and IQ
      matched controls. The patients were impaired on almost all tests studied with
      deficits in pattern and spatial recognition memory, matching to sample, spatial
      span, spatial working memory and planning. Most of the patients showed at least
      some impairment and deficits were seen across cognitive domains. An important
      finding was the detrimental effect of failure on subsequent performance; having
      solved one problem incorrectly, patients were far more likely than controls to
      fail the subsequent problem. Superimposed on the general deficits, there were
      also specific deficits in executive tasks characteristic of frontostriatal
      dysfunction and deficits in mnemonic tasks characteristic of temporal lobe
      dysfunction. This combination of a specific form of motivational deficit,
      resulting in oversensitivity to negative feedback, and superimposed specific
      neuropsychological deficits were correlated with severity of depression. The most
      significant correlations were seen between mnemonic deficits and clinical rating
      scores. Comparisons of the deficits seen in the depressed patients in this study
      with other patient groups assessed with the CANTAB neuropsychological battery,
      showed that one of the hypotheses of the neuropsychological deficits in
      depression, that of "frontosubcortical' or "frontostriatal' dysfunction, was not
      supported. These findings are discussed in relation to the likely neural
      substrates of depression.

PMID- 8878331
TI  - Lifetime co-morbidity of panic attacks and major depression in a population-based
      study: age of onset.
AB  - We used survival analysis to test for a suspected effect of co-morbidity of
      DIS/DSM-III major depression and panic attack on the age of onset of each of
      these disorders, in a population-based sample from four sites of the National
      Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program (N =
      12668). The possible effects of gender and presence of a co-morbid disorder on
      age of onset of the single disorders were analysed using the Cox proportion
      hazard-model, with gender as an explanatory variable and the co-morbid disorders
      as time-dependent covariates. The disorders begin earlier in life when they are
      co-morbid than when they occur singly. The occurrence of one disorder increases
      the chance of occurrence of the other. Females have from 1.7 to almost twice the
      risk for developing panic and/or depression compared with men, even if the co
      morbid disorder precedes the index disorder or is lifetime co-morbid. These
      findings are compatible with a hypothesis of a higher severity in co-morbid cases
      when compared with a single disorder.

PMID- 8878332
TI  - Prevalence of psychiatric morbidity in the adult population of a rural South
      African village.
AB  - We report on the first South African two-stage community prevalence study of
      psychiatric morbidity, conducted in Mamre, a rural "coloured' village, 50 km from
      Cape Town. Randomly selected adults (N = 481) were assessed using the Self
      Reporting Questionnaire (SRQ) as a first-stage screen and the Present State
      Examination (PSE-9) was administered to a proportion of the sample (N = 121) as
      the second-stage criterion. Demographic, health care utilization, and substance
      abuse data were also collected. Using the PSE-9 CATEGO Index of Definition of 5,
      the weighted prevalence of psychiatric morbidity was 27.1% (confidence interval
      of 19.5-34.7%), the majority of cases being given a tentative diagnosis of
      depressive or anxiety disorder. The CATEGO algorithm may not be fully appropriate
      in this cultural context as there was an apparent over-diagnosis of paranoid
      states. The SRQ's weighted sensitivity and specificity were 0.49 and 0.82
      respectively. Overall, the SRQ correctly identified 67% of cases and non-cases.
      No demographic variables predicted psychiatric morbidity, but there was an
      indirect link between morbidity and primary care utilization. Further South
      African studies of the validity of both the SRQ and of criterion instruments are
      needed. These may contribute to knowledge regarding cultural factors affecting
      psychiatric diagnosis.

PMID- 8878333
TI  - Impaired attention in depressive states: a non-specific deficit?
AB  - Although cognitive research on attention has advanced significantly in recent
      years, these advances have produced few specific hypotheses regarding the
      attentional impairment seen in depression, and few experiments designed to test
      them. We review the limited neuropsychological literature on impaired attention
      in depressive states, with emphasis on areas where the findings of modern
      cognitive research might be applied in the future to design more sophisticated
      tests of attentional impairment. At present, it is not possible to determine
      whether the attentional deficits seen in depression are specific to this
      disorder, or whether they represent a final common pathway of impaired cognition
      seen in many different mental and organic deficit states, such as schizophrenia
      and dementias.

PMID- 8878334
TI  - A two-stage epidemiological study of abnormal eating attitudes and their
      prospective risk factors in Polish schoolgirls.
AB  - In this longitudinal two-stage screening study of abnormal eating attitudes and
      behaviours in Polish schoolgirls self-report questionnaires (EAT-26) were
      completed by 747 schoolgirls aged between 14 and 16 years. On the basis of their
      EAT-26 scores 167 girls were selected for a clinical interview conducted blind to
      questionnaire scores. No clinical cases of DSM-III-R anorexia or bulimia nervosa
      were identified, however, there was a point prevalence of 2.34% for subclinical
      eating disorder and of 28.6% for dieting. Natural history was investigated,
      repeating the screening and interviews after 10 months. Both the group mean EAT
      26 score and the proportion of subclinical cases remained the same at follow-up
      however, individual girls showed substantial fluctuations over time. On re
      screening 11.5% of the sample had moved EAT category (based on scoring below or
      above the clinical cut-off point). Follow-up interviews showed that 58% (7) of
      the original subclinical cases were no longer cases while seven girls were "new'
      subclinical cases. This second stage of the study also aimed to investigate the
      risk factors for the development of eating disorders. Several family factors
      distinguished the dieters from non-dieters at the initial stage. Subjects who
      began dieting between the initial and follow-up interviews had higher Body Mass
      Index, felt more overweight and had greater discrepancy between their current and
      ideal weights than the non-dieters. However, analysis of regression revealed no
      specific risk factors for development of a subclinical syndrome.

PMID- 8878336
TI  - Depressive thinking: changes in schematic mental models of self and world.
AB  - Alternative explanations for the changes in thinking associated with depression
      were examined. Depressive thinking could reflect a generalized increase in
      accessibility of negative constructs and memories, previously associated with
      depression. Alternatively, depressive thinking could reflect changes at a more
      generic level of cognitive representation, related to schematic mental models. To
      investigate contrasting predictions from these two explanations, depressed
      patients and non-depressed controls completed sentence stems involving social
      approval or personal achievement e.g. 'If I could always be right then others
      would-me'. Construct accessibility views predict that depression will be
      associated with more negative completions (e.g. 'dislike'). By contrast, the
      schematic model view predicts patients may give more positive completions (e.g.
      'like'). This is because schematic models reflect inter-relationships between
      constructs, and, it is suggested, depression is associated with use of schematic
      mental models that imply closer dependence of personal worth/acceptance on
      success/approval than the models used in the non-depressed state. Predictions
      from the schematic model view were supported, confirming previous findings.
      Results suggest that depressive thinking reflects changes in the high level
      mental models used to interpret experience.

PMID- 8878335
TI  - Pre-morbid asociality in neuroleptic-resistant and neuroleptic-responsive
      schizophrenia.
AB  - The purpose of this study was to evaluate whether childhood and adolescent pre
      morbid asociality differed in neuroleptic-responsive and neuroleptic-resistant
      schizophrenia. Pre-morbid asociality was assessed with the Pre-morbid Asociality
      Adjustment Scale in 411 patients meeting DSM-III-R criteria for chronic
      schizophrenia or schizoaffective disorder categorized as being either neuroleptic
      responsive or neuroleptic-resistant. Patterns of childhood and adolescent
      asociality were found to be different in neuroleptic-resistant and neuroleptic
      responsive patients. Pre-morbid asociality during the pre-adult years was not
      consistently worse in patients with poor response to neuroleptic treatment.
      Greater impairment in late adolescent psychosexual functioning was predictive of
      poor outcome with regard to neuroleptic treatment.

PMID- 8878337
TI  - Are blunted dexamethasone-induced growth hormone responses unique to depression?
AB  - In health, acute administration of glucocorticoids, such as dexamethasone (DEX),
      leads to growth hormone (GH) secretion. Depression is characterized by blunted
      DEX/GH responses. In order to determine the specificity of this test for
      depression we administered 4 mg of oral DEX, to patients with a DSM-III-R
      diagnosis of depression, schizophrenia, mania and alcohol dependency syndrome.
      Samples for GH estimation were taken at -15 min, 0 min, +60 min, +180 min, +240
      min and +300 min. GH responses were attenuated to a similar degree in depression
      and mania. Less marked attenuation was seen in schizophrenia while those with
      alcohol dependency syndrome had GH responses indistinguishable from normal
      volunteers. Overall, we conclude that subnormal DEX/GH secretion is not specific
      to depression.

PMID- 8878338
TI  - Dementia in old age: an anthropological perspective.
AB  - This paper examines the assumption that dementia in old age is a universal
      phenomenon that will vary in its prevalence and manifestation because of social
      and cultural factors. It finds that while researchers have been successful in
      demonstrating the commonality of dementia, they have been less successful in
      showing whether or not it varies across cultures and between social and ethnic
      groupings. The inconclusiveness of findings may, in part, be a function of
      diagnostic differences and the research methodologies employed. New instruments
      and measures are being devised to overcome these problems. However, the
      sociocultural context in which dementia occurs and the meaning of the disorder to
      those involved (as sufferers and caregivers) are often missing dimensions. In
      particular, there is little knowledge about how the disorders of old age in non
      Western settings are experienced and understood. In this respect anthropology has
      a special contribution to make to research on dementia.

PMID- 8878339
TI  - Prevention of winter seasonal affective disorder by bright-light treatment.
AB  - In patients with winter seasonal affective disorder (SAD) the onset of a
      depressive episode is probably associated with the decreasing amount of light
      during the autumn. A highly predictable onset of a recurrent depressive episode
      with seasonal pattern provides a rationale for testing the efficacy of bright
      light treatment as a preventive measure. Twelve out-patients with winter SAD were
      assigned to start bright light treatment either when they were well, or not to
      start it until the first symptoms of depression had already emerged. The severity
      of depressive symptoms was prospectively rated for a parallel randomized
      comparison. Bright light given well in advance of the emerging symptoms prevented
      a depressive episode. Clinical remission was significantly more frequent in the
      former subgroup of the patients in January and in March. To sum up, bright light
      can be successfully administered as prophylactic treatment for the prevention of
      winter SAD.

PMID- 8878340
TI  - Insight, psychosis and ethnicity: a case-note study.
AB  - Recent literature on insight has paid little attention to patients' social
      backgrounds and cultures. Discharge summaries from 357 patients with a psychotic
      illness were examined to investigate factors associated with insight. A highly
      significant association was found between British white ethnic origin and being
      thought by the admitting psychiatrist to have some insight. Possible explanations
      include: different ways of understanding mental illness in different cultures,
      greater stigma leading to greater denial of illness in some cultures, greater
      illness severity at admission in some ethnic groups and racial bias in
      psychiatrists' ratings.

PMID- 8878341
TI  - The diagnostic and prognostic significance of the Whitely Index, the Illness
      Attitude Scales and the Somatosensory Amplification Scale.
AB  - The aim of this study was to assess the ability of the Whitely Index, Illness
      Attitude Scales and Somatosensory Amplification Scale to differentiate in
      patients with medically unexplained physical symptoms between hypochondriacal and
      non-hypochondriacal patients and to examine whether the scores on these
      questionnaires are predictive of long-term outcome in terms of recovery of
      presenting symptoms and number of visits to the general practitioner. The study
      population consisted of 183 consecutive patients, who presented with medically
      unexplained physical symptoms to a general medical out-patient clinic. The Health
      Anxiety subscale of the Illness Attitude Scales and the Whitely Index were best
      in discriminating between hypochondriacal and non-hypochondriacal patients. The
      sensitivity and specificity of the Health Anxiety subscale of the Illness
      Attitude Scales were 79% and 84%, and of the Whitely Index 87% and 72%. The
      Whitely Index was negatively associated with recovery rate at 1 year follow-up.
      The Illness Behaviour subscale of the Illness Attitude Scales appeared to be
      predictive of the number of visits to the general practitioner. These findings
      might have clinical implications in helping to distinguish in patients with
      medically unexplained symptoms those for whom there is a high chance of
      persistence of the symptoms and/or of high medical care utilization.

PMID- 8878342
TI  - Serotonergic modulation of striatal D2 dopamine receptor binding in humans
      measured with positron emission tomography.
AB  - The modulating effect of serotonergic drugs on the striatal dopamine
      neurotransmission has remained controversial, and there are no published data on
      serotonin-dopamine interaction obtained from living human brain. Citalopram is a
      selective serotonin reuptake inhibitor widely used in the treatment of depression
      (20-40 mg/day). We measured the effects of acute (20 mg, per os) and chronic (20
      mg/day for 14 days) doses of citalopram and placebo intake on [11C]-raclopride
      binding to striatal D2-receptors in eight healthy volunteers by using positron
      emission tomography. Although the effect magnitude was not large, the results
      indicate that chronic citalopram intake slightly decreases the raclopride binding
      which may reflect increased dopamine release in the striatum. In addition, after
      14 days there was a high correlation between the citalopam plasma levels and the
      decrease in the [11C]-raclopride binding in both the caudate and the putamen,
      although statistically significant effect in the raclopride binding potential was
      more pronounced in the putamen. This report suggests functional interaction of
      brain dopaminergic and serotonergic systems in vivo in man.

PMID- 8878343
TI  - Oral caffeine pretreatment produced modest increases in smoked cocaine self
      administration in rhesus monkeys.
AB  - Several recent studies have shown that caffeine potentiates the reinforcing,
      discriminative stimulus, and motor activating effects of cocaine in rats. The
      present study was designed to determine whether oral caffeine pretreatment would
      enhance the reinforcing effects of cocaine in rhesus monkeys trained to self
      administer smoked cocaine base. The effects of oral caffeine pre-treatment (0,
      100, or 200 mg) and fixed-ratio (FR) value on cocaine-base smoking were evaluated
      in four male rhesus monkeys. Monkeys responded on a lever under a fixed-ratio
      (FR) schedule (FR 128, 256, 512, 1024, 2048, or 4096) and then made five
      inhalations on a smoking spout to gain access to volatilized cocaine base (0.25
      or 1.0 mg/kg per delivery) during daily experimental sessions. Twenty pellets [20
      non-caffeinated (0 mg caffeine), ten non-caffeinated+ten caffeinated (100 mg
      caffeine), or 20 caffeinated (200 mg caffeine) pellets] were administered 30 min
      prior to experimental sessions. The lever FR value was held constant within each
      experimental session, but was increased after 3 consecutive days of stable
      responding. Although the number of smoke deliveries that was self-administered
      significantly decreased from FR 128 to FR 4096, it did not change as a function
      of cocaine dose across the range of FR values tested. However, the interaction
      between cocaine dose and caffeine pretreatment was statistically significant.
      Compared to 0 mg caffeine, three of four monkeys pretreated with 200 mg caffeine
      responded for a greater number of smoke deliveries when they were maintained on a
      cocaine dose of 1.0 mg/kg per delivery, but not 0.25 mg/kg per delivery. Thus,
      caffeine pretreatment can produce small, but statistically significant increases
      in smoked cocaine self-administration in rhesus monkeys.

PMID- 8878344
TI  - Evaluation of the cocaine-like discriminative stimulus effects and reinforcing
      effects of modafinil.
AB  - Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychostimulant
      drug which is effective in the treatment of narcolepsy and idiopathic
      hypersomnia. It also has neuroprotective effects in animal models of striatal
      neuropathology. Although the cellular mechanisms of action of modafinil are
      poorly understood, it has been shown to have a profile of pharmacological effects
      that differs considerably from that of amphetamine-like stimulants. There is some
      evidence that modafinil has central alpha 1-adrenergic agonist effects. In the
      present study modafinil was evaluated for cocaine-like discriminative stimulus
      effects in rats and for reinforcing effects in rhesus monkeys maintained on
      intravenous cocaine self-administration. Modafinil, l-ephedrine and d-amphetamine
      all produced dose dependent increases in cocaine-lever responding, with maximal
      levels of 67%, 82% and 100%, respectively. Modafinil produced full substitution
      in four out of the six rats tested while the highest levels of substitution were
      associated with substantial response rate decreasing effects. Little evidence was
      obtained that the discriminative stimulus effects of modafinil were produced by
      alpha 1-adrenergic activation, based upon results of tests performed in
      combination with prazosin. In the self-administration procedure, modafinil and l
      ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and
      discriminative stimulus effects of modafinil-required very high doses: modafinil
      was over 200 times less potent than d-amphetamine and was also less potent than l
      ephedrine. These results show that modafinil has some cocaine-like discriminative
      stimulus effects and, like other abused stimulants, can serve as a reinforcer at
      high doses.

PMID- 8878345
TI  - Importance of post-drug environmental factors for induction of sensitization to
      the ambulation-increasing effects of methamphetamine and cocaine in mice.
AB  - Mice given five repeated administrations of methamphetamine (MAP: 2 mg/kg SC) or
      cocaine (COC: 20 mg/kg SC) at 3-day intervals in a round tilting-type activity
      cage (20 cm in diameter) showed sensitization to the ambulation-increasing effect
      of each drug. The mean 3- or 2-h overall activity count at the fifth
      administration of MAP or COC, respectively, was 2.3-2.5 times higher than that at
      the first administration. Mice given MAP or COC 4 times in round spaces (15-30 cm
      in diameter), where the floor did not tilt, exhibited sensitization as strong as
      that demonstrated by mice given each drug in the activity cages, when the mice
      were given the fifth administration in the activity cages. In contrast, mice
      repeatedly given the drugs in spaces 4-9 cm in diameter never, and those in space
      12 cm in diameter only partially, exhibited sensitization to MAP and COC.
      Furthermore, mice given MAP or COC 4 times in their home cages (25D x 20W x 15H
      cm, with ten mice in each cage) showed partial sensitization. Repeated
      administration of saline to mice in activity cages, in the spaces 4-30 cm in
      diameter, or in the home cages did not cause significant change in the
      sensitivity to either MAP or COC. These results suggest that repeated experience
      of the stimulant effect of drug and the resultant ambulation is required for
      induction of sensitization to MAP and COC in terms of ambulation in mice. It is
      also suggested that spaces larger than 12 cm in diameter, which correspond to 2
      2.5 times as long as the body length without tail, and no interference from other
      mice are required for induction of strong sensitization to both MAP and COC.

PMID- 8878346
TI  - Effects of environmental conditioning on the development of nicotine
      sensitization: behavioral and neurochemical analysis.
AB  - We have investigated the effects of environmental conditioning on the induction
      of nicotine sensitization of locomotion, stereotypy and nucleus accumbens
      dopamine release. Sprague-Dawley rats, some of which had been previously
      implanted with a microdialysis guide cannula over the nucleus accumbens, were
      sensitized with 5 days of repeated nicotine (0.6 mg/kg per day, SC) or saline
      injections (1 ml/kg per day). During nicotine treatment the drug administration
      was either paired with the microdialysis/activity monitor testing chamber
      (conditioned) (n = 6) or with the animal's home cage (unconditioned) (n = 6) and
      after 60 min the animal was returned to home cage and received a second injection
      of saline 15 min later. A third group received saline in the testing apparatus
      followed by nicotine in the home cage (pseudo-conditioned) (n = 6). In the guide
      cannulated animals, 2 mm microdialysis probes were inserted after completing day
      5 of treatment and all animals were tested for their response to nicotine (0.6
      mg/kg, SC) on day 6. Both locomotor activity and nucleus accumbens dopamine
      release showed a larger response subsequent to nicotine challenge in the nicotine
      versus saline pretreated animals in the conditioned group, but not in the
      unconditioned group. In the pseudo-conditioned group there was an increase in the
      stereotypy responses to nicotine, however the locomotor and dopamine release
      responses were not significantly enhanced. The results from the conditioned group
      were confirmed in animals which were tested for behavioral activation and
      dopamine release simultaneously (n = 5). These findings indicate that nicotine
      sensitization of locomotor activity and nucleus accumbens dopamine release (using
      a 5-day pretreatment protocol) is dependent on conditioning the animal to the
      testing environment during nicotine pretreatment.

PMID- 8878347
TI  - Effects of dopamine agonists and antagonists on cocaine-induced operant
      responding for a cocaine-associated stimulus.
AB  - The present study examined the effects of receptor subtype-selective dopamine
      agonists and antagonists on (i) cocaine-induced responding for a cocaine
      associated stimulus and (ii) on responding for food and cocaine reinforcement.
      Rats implanted with intravenous catheters were trained to lever-press for food or
      cocaine reinforcers on an FR5-FR5 multiple schedule, which was preceded by a 5
      min component during which only stimuli previously associated with the primary
      reinforcers were available response-contingently. (i) Non-contingent delivery of
      cocaine at the beginning of the stimulus component significantly increased
      responding for the cocaine-associated stimulus, compared to responding for the
      food-associated cue. Changes in the dose of cocaine administered non-contingently
      before the stimulus component resulted in an inverted U-shaped dose-effect curve
      in responding for the cocaine-associated cue. In subsequent experiments,
      pretreatment with the dopamine D2 receptor agonist bromocriptine (4.0-16.0 mg/kg
      IP) attenuated the cocaine-induced increase in responding for the cocaine
      associated cue. In contrast, pretreatment with low doses of SDZ 208-911, a
      dopamine D2 partial agonist (0.025-0.1 mg/kg SC), further potentiated the cocaine
      induced response. Pretreatment with low and medium doses of the dopamine D1 and
      D2 receptor subtype-selective antagonists SCH 23390 (D1; 5-10 micrograms/kg SC)
      and raclopride (D2; 100-200 micrograms/kg SC) blocked responding for cocaine
      associated cues, with SCH 23390 acting more selectively than raclopride. At
      higher doses (SCH 23390: 20 micrograms/kg SC; raclopride: 400 micrograms/kg SC),
      both drugs produced non-selective effects by inhibiting responses for the food
      associated cue. (ii) Varying the dose of cocaine self-administered during the
      multiple schedule resulted in an inverted U-shaped dose-effect curve during the
      cocaine components, while the number of food pellets earned remained unchanged.
      Pretreatment with bromocriptine selectively reduced the number of cocaine
      infusions obtained. The compensatory increases in responding for cocaine
      typically associated with SCH 23390, raclopride or SDZ 208-911 pretreatment were
      also observed under the present schedule conditions, although the effect did not
      reach statistical significance in the case of SCH 23390 and raclopride, possibly
      due to methodological constraints. The results indicate that the present rat
      model of cocaine-seeking behavior is sensitive to pharmacological manipulations
      and may yield important information regarding the neurobiological mechanisms
      underlying conditioned and unconditioned reinforcing aspects of cocaine
      addiction.

PMID- 8878348
TI  - The neurosteroid pregnenolone sulfate reduces learning deficits induced by
      scopolamine and has promnestic effects in mice performing an appetitive learning
      task.
AB  - The effects of the neurosteroid pregnenolone sulfate (PS) on learning as well as
      on scopolamine-induced learning deficits were studied in Swiss mice using an
      appetitively reinforced Go-No Go visual discrimination task. Subcutaneous (SC)
      administration of scopolamine (0.3-3 mg/kg) after the first session of training
      dose-dependently impairs learning during the following sessions in this task.
      Moreover, intracerebroventricular (ICV) administration of PS (0.01-10 nmol) dose
      dependently blocks learning deficits induced by scopolamine (3 mg/kg), with the
      most potent effects at the dose of 0.5 nmol PS. In addition to antagonizing the
      amnestic effects of scopolamine, PS (0.5 nmol ICV) has a memory-enhancing effect,
      when administered alone after the first training session. Scopolamine (3 mg/kg
      SC) also produced substantial deficits on retrieval performance in the Go-No Go
      visual discrimination task, and caused motor disturbances, when administered 15
      min before testing. PS (0.5 nmol ICV) also reduced scopolamine-induced deficits
      on retrieval but had no effect on scopolamine-induced motor impairments in the
      traction reflex test. Such a rapid effect of PS on memory processes may be
      mediated via NMDA and/or GABAA receptors.

PMID- 8878349
TI  - Effects of intermittent and continuous cocaine administration on dopamine release
      and uptake regulation in the striatum: in vitro voltammetric assessment.
AB  - Chronic daily injections of cocaine induce behavioral sensitization to subsequent
      cocaine challenge, while continuous infusion induces tolerance. Following a 7-day
      withdrawal period, we examined the effects of these two dosing regimens on: (1)
      baseline dopamine efflux and uptake following single-pulse electrical
      stimulation, (2) inhibition of uptake by cocaine; and (3) inhibition of efflux by
      autoreceptor activation. Cocaine (40 mg/kg per day) was administered to rats for
      14 days either continuously by osmotic minipumps or intermittently by once-a-day
      injections. Minipumps containing saline were implanted in the control group.
      After 7 days of withdrawal, dopamine kinetics in the caudate was examined using
      in vitro fast-scan cyclic voltammetry. This technique provides very rapid
      measurements of dopamine in the extracellular space. Thus, when combined with
      endogenous dopamine efflux evoked by single-pulse, electrical stimulations, it
      was possible directly to measure the release and uptake components of the efflux.
      In the absence of pharmacological agents, no group differences were found in the
      amount of baseline dopamine released or in the uptake kinetics; the potency of
      bath-applied cocaine (0.03-60 microM) in inhibiting the uptake was also unaltered
      in either group. In contrast, the potency of quinpirole (an autoreceptor agonist,
      5-250 nM) was significantly decreased and increased in the cocaine injection and
      pump groups, respectively. Thus, the cocaine administration regimen which
      produces sensitization results in a functional subsensitivity of release
      modulating autoreceptors, while the tolerance-producing regimen results in
      autoreceptor supersensitivity.

PMID- 8878350
TI  - Pentagastrin has panic-inducing properties in obsessive compulsive disorder.
AB  - The effects of the CCKB-receptor agonist pentagastrin, a synthetic analogue of
      the cholecystokinin tetrapeptide (CCK-4), were studied in seven patients
      suffering from obsessive compulsive disorder (OCD) and seven healthy controls.
      All subjects were challenged with an IV dose of 0.6 micrograms/kg pentagastrin or
      placebo under double blind placebo controlled conditions, on two separate
      occasions, with a minimum interval of 1 week. Six (86%) out of seven OCD patients
      experienced a panic-like reaction after pentagastrin administration, against only
      two (29%) in the control group. These differences failed to reach statistical
      significance, probably due to the small sample size. No increases were observed
      in obsessions or compulsive behaviors as assessed with the Yale-Brown Obsessive
      Compulsive Challenge Scale, neither in the pentagastrin, nor in the placebo
      condition. These findings suggest that pentagastrin has panic-inducing properties
      in OCD patients, without affecting the core symptoms. The panic-inducing
      properties of pentagastrin are not specific for panic disorder patients, which
      might be indicative of a common neurobiological dysfunction in panic disorder and
      OCD at the level of CCK-B receptors.

PMID- 8878352
TI  - Nutritional and metabolic aspects of postprandial lipemia.
AB  - The present review deals with the nutritional and metabolic aspects of
      postprandial lipemia. The postmeal state is characterized by the accumulation of
      triglyceride-rich lipoproteins (TRL) in the plasma. This is due to the
      competition for clearance between hepatically-derived very low density
      lipoproteins (VLDL) and intestinally-derived chylomicrons. At the same time, an
      important remodeling of the low density lipoprotein (LDL) and high density
      lipoprotein (HDL) particles takes place. The amplitude and/or time-course of the
      occurrence of the postprandial triglyceride response is influenced by the
      quantity of dietary lipids (triglycerides, cholesterol), the fatty acid
      composition of dietary triglycerides and the amount and nature of dietary
      carbohydrates and fibers. The preexisting metabolic status of the subjects
      markedly influences the postprandial response; i.e., hyperlipidemic, diabetic and
      obese subjects can exhibit an exaggerated increase in triglycerides and
      lipoprotein remodeling. The hypothesis that postprandial lipid modifications are
      associated with atheroma deposition and coronary events has been supported by
      several experimental observations. Despite the significant amount of knowledge
      already obtained in this field, further research is needed to better elucidate
      the existing relationships between dietary intake, postprandial response and
      pathological events.

PMID- 8878351
TI  - The effect of alpha 2 adrenoceptor blockers on aggressive behavior in mice:
      implications for the actions of adrenoceptor agents.
AB  - The effects of three alpha 2 adrenoceptor blockers (idazoxan, yohimbine and CH
      38083) on isolation-induced aggressive behavior was studied in male mice. The
      three drugs produced different behavioral profiles. Idazoxan reduced
      aggressiveness dose-dependently by decreasing the duration of
      offensive/aggressive interactions and increasing the duration of defensive
      behaviors. The other two drugs produced only parts of the dual action of
      idazoxan: yohimbine affected mainly defensive behaviors, while CH-38083 affected
      only the time spent with fighting. Saline injections per se also influenced
      behavior and, in contrast to alpha 2 adrenoceptor blockers, induced an increase
      in aggressiveness. These results are different from those previously obtained in
      rats, which show bell-shaped dose-response curves in response to alpha 2
      adrenoceptor blockers (small doses increased, while large doses decreased
      aggression). It is postulated that the strong behavioral reaction of mice to the
      injection per se may mask the aggression-heightening effects of small doses of
      alpha 2 adrenoceptor blockers in this species. A theory is also presented
      regarding the complexity of adrenoceptor interactions when both pre-, and
      postsynaptic alpha 2 adrenoceptors are blocked.

PMID- 8878353
TI  - Role of glucokinase and glucose-6 phosphatase in the nutritional regulation of
      endogenous glucose production.
AB  - Two specific enzymes, glucokinase (GK) and glucose-6 phosphatase (Glc6Pase)
      enable the liver to play a crucial role in glucose homeostasis. The activity of
      Glc6Pase, which enables the liver to produce glucose, is increased during short
      term fasting, in agreement with the enhancement of liver gluconeogenesis. During
      long-term fasting, Glc6Pase activity is increased in the kidney, which
      contributes significantly to the glucose supply at that time. On the other hand,
      GK activity, which allows the liver to utilize glucose, is decreased during
      fasting. In the fed state, the mechanisms of short-term regulation of the
      activity of both enzymes takes place during the postprandial period. Liver
      GlcPase activity is inhibited after refeeding in rats. The inhibition mechanism
      could involve intracellular metabolites of glutamine and glutamic acid, such as
      alpha-ketoglutarate, and/or of triglycerides, such as unsaturated fatty acids and
      acyl-CoA esters. Liver GK activity is activated during the postprandial period.
      The activation mechanism involves a regulatory protein and the intrahepatic
      metabolites of fructose, ie fructose-1 phosphate and fructose-6 phosphate.

PMID- 8878354
TI  - New methods for in vivo studies of hepatic metabolism.
AB  - In vivo studies of liver metabolism have been limited for a long time to
      measurements, by the balance technique or the isotope dilution method, of the
      amounts of substrates taken up or produced by liver. New methods have been
      developed that now permit us to obtain important information on intrahepatic
      metabolic pathways. Nuclear magnetic resonance permits noninvasive studies of
      liver glycogen synthesis and breakdown. Chemical biopsy of glucuronic acid by
      acetaminophen also permits the study of glycogen synthesis whereas chemical
      biopsies of liver glutamine by phenylacetate and of cytosolic acetyl-CoA by
      sulfamethoxazole give important information concerning, respectively, Krebs cycle
      activity and glconeogenesis and on lipogenesis and cholesterol synthesis. Mass
      isotopomer distribution analysis of molecules synthesized during the infusion of
      a deuterium of 13C-labeled precursor permits the estimation of in vivo
      gluconeogenesis as well as cholesterol synthesis and lipogenesis. Finally, these
      metabolic pathways can be studied through the incorporation of deuterium from
      deuterated water in glucose, fatty acids and cholesterol. All these noninvasive
      techniques will allow investigations to be undertaken in humans, addressing the
      nutritional and hormonal regulation of liver metabolism in normal subjects and in
      pathological situations.

PMID- 8878355
TI  - Regulation of VLDL synthesis and secretion in the liver.
AB  - The production of very low density lipoproteins (VLDL) by the liver results from
      very complex processes that involve coordinated mechanisms of both protein and
      lipid synthesis and packaging. Alterations in these metabolic functions can cause
      negative effects on the health of human subjects or animals. The objectives of
      this paper were to review the latest developments in the biological mechanisms of
      these processes and the role of nutritional and hormonal factors. The present
      study addresses the following issues: i) the main steps in the hepatic metabolism
      of lipids (long-chain fatty acids, triacylglycerols, phospholipids) and proteins
      (apolipoprotein B, microsomal transfer protein) primarily involved in the
      synthesis and secretion of VLDL particles; ii) the metabolic deviations of
      hepatic VLDL (hypo- and overproduction) in man, rodents and farm animals
      (poultry, dairy cows).

PMID- 8878356
TI  - Thermic effect of food and sympathetic nervous system activity in humans.
AB  - The intake of nutrients is known to increase energy expenditure. Measured thermic
      effects of nutrient are 0-3% for fat, 5-10% for carbohydrates and 20-30% for
      proteins. Stimulation of adenosine triphosphate (ATP) hydrolysis during
      intestinal absorption, initial metabolic steps and nutrient storage are
      responsible for this food thermic effect. The autonomic nervous system modulates
      the thermic effect of nutrients. Parasympathetic muscarinic antagonists reduce
      the thermic effect of orally administered nutrients, most likely by delaying
      gastric emptying and decreasing the amount of nutrient storage. Antagonists of
      the beta-adrenoreceptors decrease the thermic effect of glucose. The part of
      glucose induced thermogenesis which is eliminated by beta-adrenergic antagonists
      has been called 'facultative thermogenesis' and takes place, at least in part, in
      skeletal muscle. Insulin-induced stimulation of muscle sympathetic nerve activity
      may be involved in this facultative thermogenesis. The thermic effect of food is
      reduced in obese, insulin-resistant patients. The effect of thermogenesis
      represents about 50-150 kcal/day in such patients, and can explain only a minor
      part of their excess body weight. Defective thermogenesis may, however,
      contribute to weight gain, or impair weight loss in such patients.

PMID- 8878357
TI  - Regulation of net hepatic glucose uptake: interaction of neural and pancreatic
      mechanisms.
AB  - Insulin and glucagon levels, the mass of glucose presented to the liver and the
      portal signal are important regulators of the liver's response to glucose
      delivery. The portal signal not only serves to direct glucose into the liver but
      also appears to stimulate its deposition in glycogen. Moreover, the portal signal
      impacts on tissues other than the liver: intraportal glucose delivery is
      associated with changes in glucose uptake by nonhepatic tissues and neurally
      mediated enhancement of pancreatic insulin secretion. Our current understanding
      of the neural control of hepatic glucose metabolism includes a tonic block to the
      entry of glucose into the liver, probably mediated both by sympathetic neural
      activity and by a low insulin:glucagon ratio. An increase in the portal vein
      glucose level is detected by sensors in the portal region, which cause a decrease
      in the firing rate in the hepatic branch of the vagus nerve. The change in the
      afferent firing rate is processed in the hypothalamus and instigates a change in
      the efferent firing rate in the hepatic and pancreatic branches of the vagus
      (with corresponding increases in insulin secretion and net hepatic glucose
      uptake). The portal signal thus relieves the sympathetic inhibition of hepatic
      glucose uptake and enhances hepatic glucose uptake directly by stimulating the
      parasympathetic innervation to the liver and indirectly by enhancing insulin
      release.

PMID- 8878358
TI  - Responses to requests for clarification by older and young adults with mental
      retardation.
AB  - This study compared the ability of young (mean chronological age = 29 yrs., SD =
      3.67 yrs.) and older adults (chronological age = 63 yrs., SD = 5.54 yrs.) with
      mild to moderate mental retardation to respond to stacked requests for
      clarification in conversation. Data were collected in dyadic conversations
      between subject and investigator. During the course of the conversation, the
      investigator introduced stacked sequences of three requests for clarification of
      the same message ("Huh?", "What?", "What?"). Neither group of subjects was as
      responsive to the requests for clarification as would have been predicted based
      on their general cognitive and linguistic levels of functioning. Few significant
      differences were observed between the young and older groups.

PMID- 8878359
TI  - Assessment and treatment of episodic self-injury: a case study.
AB  - Functional analysis probes were conducted over an extended time period to
      identify the consequences that maintained infrequent self-injury (occurred 1-5
      days monthly). Occurrences of respite care and episodes of physical illness were
      concurrently measured in order to assess their influence on response-reinforcer
      relations during functional analysis conditions. Functional analysis of immediate
      antecedents and consequences produced inconclusive results. A subsequent
      systematic manipulation of respite care demonstrated a relationship between the
      presence of self-injury and the occurrence of respite the previous evening. The
      intervention consisted of altering the respite situation, which resulted in the
      long-term elimination of self-injury.

PMID- 8878360
TI  - Focus on communication: improving interaction between staff and residents who
      have severe or profound mental retardation.
AB  - The purpose of the present research project was to examine change in interactive
      behaviors between staff and residents of facilities that serve individuals with
      mental retardation. Twelve staff members were trained using an adapted component
      of the Nursing Child Assessment Satellite Training model, the Mental
      Retardation/Developmental Disabilities Adaptation of the Nursing Child Assessment
      Feeding Scale. Data indicated some slight increases in positive interactive staff
      behaviors with some small indications of generalization to another task and
      maintenance over a 6-month period in one setting. Little or inconsistent change
      was indicated in resident behaviors. Recommendations are made for further
      investigation of factors related to behavior change in staff and residents.

PMID- 8878361
TI  - Age and IQ as predictors of emotion identification in adults with mental
      retardation.
AB  - The effects of age and IQ on the identification of six emotions were assessed for
      adults with mental retardation. Emotion perception was tested in three paradigms:
      a short vignette was read, and the individual was asked to choose a pictorial
      representation of a facial expression which corresponded to the vignette; a short
      vignette was read, and the individual was asked to choose a word that
      corresponded to the vignette; and a word was read, and the individual was asked
      to choose a pictorial representation of a facial expression that corresponded to
      the word. Age correlated negatively with performance in the two conditions in
      which choosing a facial expression was used as a response. IQ significantly
      predicted performance in all three conditions. A decrease in right hemisphere
      processing abilities with age was suggested as one possible explanation for the
      findings.

PMID- 8878362
TI  - A review of choice research with people with severe and profound developmental
      disabilities.
AB  - During the last 15-20 years, a significant amount of research has focused on the
      issue of choice among people affected by severe-profound developmental
      disabilities. Studies have been directed at (a) assessing the ability of those
      people to choose between different options and express preferences that could be
      used for reinforcement or occupational purposes, (b) building choice
      opportunities within those people's daily situations, and (c) evaluating the
      possible effects of choice making on those people's performance and behavior.
      This paper reviews the aforementioned studies and comments on the main findings
      and related questions.

PMID- 8878364
TI  - Development and status of social medicine in Germany.
AB  - The current status of scientific social medicine in the Federal Republic of
      Germany is presented against the background of historical development. Ideas
      differ when it comes to identity, academic institutionalisation, the main
      emphasis of work, the syllabus and future tasks. The heterogenic diversity of the
      subject is emphasised by the lack of any generally accepted definition. There is
      a current tendency to regard social medicine exclusively as population medicine
      rather than more generally as the interaction between disease/health, general
      social system and the individual. Clinical practical social medicine,
      epidemiology, health system research/health economy, and public health can be
      distinguished as important occupational fields. Acquiring the additional title in
      social medicine is widely recognised as the necessary further training. However,
      the discussion about improving the training in social medicine at German
      universities is still causing much controversy. Secure anchoring within the canon
      of medical subjects is of particular importance regarding the totality of the
      subject and its future in medical faculties.

PMID- 8878363
TI  - [Study by questionnaire of the influence of weather conditions, particularly fog,
      on the symptomatology of asthmatic subjects].
AB  - The role of fog in the symptomatology in asthmatic subjects has been assessed by
      a questionnaire concerning respiratory complaints linked to meteorological
      conditions and to non-specific irritant factors. In a population of 121
      asthmatics (59 men and 62 women) 74.4% complained that fog was a factor
      aggravating their symptoms while only 3% of a group of 30 non-asthmatic subjects
      expressed discomfort during episodes of fog. The chemical analysis of fog during
      32 episodes of local fog (pH, chloride, nitrate, sulphate, sodium, ammonia,
      potassium, magnesium, calcium) has shown a greater concentration of pollutants
      and greater acidity in the smaller particles (2-6 microns) which are able to
      penetrate the bronchial tree. This acidity could explain the role of fog in
      respiratory physiology. Certain authors have suggested that the aggravation of
      respiratory symptoms observed during peaks of pollution could be induced by
      aerosols containing sulphuric acid while others have described effects on
      respiratory function at the time of exposure to acid aerosols in asthmatic
      subjects but the results of the different studies have not all been concordant.
      Putting aside the role of the susceptible individual, other factors may intervene
      at the time inhalation of pollutants, notably the ambient humidity, the
      neutralising effect of endogenous ammonia and the synergystic effect between acid
      aerosols and atmospheric pollutants.

PMID- 8878365
TI  - Social medicine and the United States.

PMID- 8878366
TI  - Knowledge of prenatal care among non-pregnant women: an explanation for early
      attendance.

PMID- 8878367
TI  - Is foetal growth reduction induced by smoking modified by body mass or
      gestational weight gain?

PMID- 8878368
TI  - Support to drug-addicted parents: a help to the children?

PMID- 8878369
TI  - Appraisal, coping, motivational factors and gender in vocational rehabilitation.
AB  - The applicability of a model of appraisal and coping was studied in vocational
      rehabilitation patients (n = 31:16 men, 15 women); the selection of patients
      aimed at obtaining a representative patient group for studying coordinated
      rehabilitation within various health care districts in southern Sweden. There
      were four phases of data collection and model adjustment. An initial, semi
      structured interview concerned various key topics (program evaluation; causal
      attribution regarding the problem or disease; life-crises, threats, mobbing and
      unjust treatment; feeling of control; current situation; future; how the
      interview was experienced). The second phase involved a questionnaire study of
      hypochondriacal and depressive symptomatology, the third the analysis of patient
      records, and the fourth outcome data on sickness allowances and disability
      pensions at a 2-year follow-up. The results indicate the importance for
      rehabilitation of attending to motivational factors that influence the patients'
      coping strategies and appraisal, and to cultural (immigrant) and gender
      perspectives.

PMID- 8878370
TI  - Impact of pregnancy on gender differences in sickness absence.
AB  - Women in general have a higher sickness absence than men, and sickness absence is
      particularly high among pregnant women. STUDY OBJECTIVES: To study the level of
      male sickness absence as compared to female, including and excluding pregnant
      women. DESIGN: Studies of incidence and length of sickness absence exceeding 7
      days using population-based sick-leave records. SETTING: The community of
      Linkoping, Sweden, 117,000 inhabitants. PARTICIPANTS: Subjects included in the
      analysis were all men and women aged 16-44 who in 1985 or 1986 had at least one
      sick-leave spell exceeding 7 days. RESULTS: Pregnant women had a very high
      sickness absence. When pregnant women were excluded, the female sick-leave rate
      decreased from 0.18 (95% C.I. 0.17-0.18) to 0.15 (95% C.I. 0.15-0.16) for all
      women. The corresponding male sick-leave rate was 0.12 (95% c.i. 0.12-0.13).
      Gender differences in length of sickness absence decreased to the same extent.
      The results were similar when restricting the analysis to employed persons. The
      decrease varied a little with occupational group and was largest in the age-group
      25-34. CONCLUSIONS: When pregnant women were excluded the excess female sick
      leave rate was halved, but still remained 25% higher than the male. The impact of
      excluding pregnant women was highest in the age group 25-34, where the fertility
      rate was highest. Although only 5% of all women aged 16-44 were pregnant, they
      had a large impact on gender differences in sickness absence.

PMID- 8878371
TI  - The Swedish UPA score: an administrative tool for identification of
      underprivileged areas.
AB  - The purpose was to construct a Swedish social deprivation index analogous to the
      underprivileged area (UPA) score, used in the UK to distribute resources to
      general practice for patients resident in the most underprivileged areas. UPA
      scores were calculated using 1990 Swedish census data and the 1992 unemployment
      and migration registers for all 8,502 SAMS (small area market statistics) areas
      with more than 50 inhabitants. Selection of the eight variables included in the
      score and weights attached to each were derived from a national survey of general
      practitioners in the UK representing the degree to which they considered that
      each factor increased their workload or pressure on services. The UPA score for
      each area is the sum of the eight normalised (arc sin square root), standardised
      (z scores) and weighted variables for that area. The distribution of UPA scores
      ranged from -79.13, in the most affluent areas to 46.10 in the most
      underprivileged areas. It was found that a wide range of social deprivation
      exists at small area level.

PMID- 8878372
TI  - Mental impairment and utilization of community services: a study of the elderly
      in a parish of Stockholm.
AB  - Before the implementation of the health care reform of 1992 (The Adel Reform), a
      study of the frequency of mental impairment of people in different residential
      and care services was conducted in a parish of Stockholm. All residents, 65 years
      or older, registered with Primary Care Centres, Geriatric Hospitals and other
      institutions were assessed with respect to cognitive function according to the
      seven stage "Global Deterioration Scale" (GDS). The age-specific frequencies of
      mental impairment were similar to prevalences reported in earlier studies. The
      frequency of cognitive dysfunction of non-institutionalized and institutionalized
      elderly was 42% and 52%, respectively, and higher for women than for men. There
      was considerable variation in the prevalence of cognitive dysfunction among
      subjects in different types of accommodation. For the different stages of mental
      impairment the average age was about the same. With increasing need and demand
      for services, and limited resources, these variations in cognitive dysfunction
      have important implications for structuring appropriate support systems in a
      population with a rapidly rising proportion of elderly people.

PMID- 8878373
TI  - Disease course and prognosis in rheumatoid arthritis: an interdisciplinary
      prospective longitudinal study.
AB  - A three-year follow-up of individuals with rheumatoid arthritis was performed.
      The overall aim was to examine the change in functional status and psychological
      well-being. Possible determinants of prognosis with regard to future functional
      disability, pain and wellbeing, were explored by both univariate and multiple
      regression analyses. Functional disability, pain and well-being were fairly
      stable over the 3-year period. Progress of RA disease was most strongly related
      to initial function and age and only to a minor extent to the psychological well
      being.

PMID- 8878374
TI  - Trends in diagnosis-specific mortality for the aging population in Norway, 1966
      1986.
AB  - For the older segment of the Norwegian population, sex, age at time of death, and
      time-period of death are important factors to consider when describing cause
      specific mortality trends. Correspondence analysis was applied to mortality and
      provided plots which in a conceptually simple way demonstrated the complex
      relations between sex, age, time-periods and causes of death. Log-linear
      modelling was used to confirm the findings of the correspondence analyses. During
      the period of observation, the elderly, regardless of sex, have experienced
      greater changes in the most important causes of death, than the younger segments
      of the population. The main intention of this article is to improve the
      conceptual understanding of how important parameters are associated with trends
      in mortality rates for the major causes of death in Norway.

PMID- 8878375
TI  - Item bias in self-reported functional ability among 75-year-old men and women in
      three Nordic localities.
AB  - The purpose of this article is to analyse item bias in a measure of self-reported
      functional ability among 75-year-old people in three Nordic localities. The
      present item bias analysis examines whether the construction of a functional
      ability index from several variables results in bias in relation to geographical
      locality and gender. Information about self-reported functional ability was
      gathered from surveys on 75-year-old men and women in Glostrup (Denmark),
      Goteborg (Sweden) and Jyvaskyla (Finland). The data were collected by structured
      home interviews about mobility and Physical activities of daily living (PADL) in
      relation to tiredness, reduced speed and dependency and combined into three
      tiredness-scales, three reduced speed-scales and two dependency-scales. The
      analysis revealed item bias regarding geographical locality in seven out of eight
      of the functional ability scales, but nearly no bias in relation to gender in the
      combined data. The conclusion is that only one tiredness-scale (Lower Limb-T),
      one reduced speed-scale (Lower Limb-S) and the two dependency-scales (PADL-H and
      Mob-H) can be proposed for use in comparisons between the three localities (with
      removal of one or more items).

PMID- 8878376
TI  - Assessing reliability of a measure of self-rated health.
AB  - The test-retest reliability of self-rated health is analysed and compared with
      the reliability of health questions phrased more as well as less precisely.
      Differences in reliability between men and women and between age groups are also
      assessed. The study is based on 204 and 409 re-interviews from the 1991 Swedish
      Level of Living Survey and the 1989 Survey of Living Conditions respectively. The
      results show that the reliability of self-rated health is as good as or even
      better than that of most of the more specific questions. Only an indicator of
      high blood pressure showed significantly higher reliability. The reliability of
      self-rated health is good in all subgroups studied, and is even excellent among
      older men. It is concluded that the good overall reliability of self-rated health
      found in this study is in line with previous results concerning the validity of
      people's assessments of their general health as well as results concerning the
      basis upon which they make these judgements.

PMID- 8878378
TI  - Rat whole-limb viability after cold immersion using University of Wisconsin and
      Euro-Collins solutions.
AB  - The purpose of this study was to compare University of Wisconsin (UW) solution
      with Euro-Collins (EC) solution in their cold preservation effects on rat limbs.
      Thirty-six Lewis rat limbs were preserved in EC solution (n=18) or UW solution
      (n=18) at 4 degrees C for 72 hr, and grafted orthotopically to a syngeneic rat
      using microsurgical techniques. The surgeon was blinded to the solution used. We
      evaluated the vascular patency rate and death rate of both groups at day 7 after
      surgery and performed histological evaluations of bone, muscle, growth plate, and
      articular cartilage for each specimen of successful grafts in both groups. The
      vascular patency rates of the EC and UW groups were 27.7% (5/18) and 11% (2/18),
      respectively, and showed no significant difference. The death rates of the EC and
      UW groups were 50% (9/18) and 60% (10/18), which were not significantly
      different. There were no clear differences in histological viability between both
      groups, in all tissues exclusive of bone marrow and muscle tissue. Our results
      showed that in comparing EC and UW solutions, one was not significantly superior
      to the other as a cold immersion storage medium after a 72 hr ischemia-induced
      reperfusion injury.

PMID- 8878377
TI  - Extending the margin of safety of preservation period for resuscitation of
      ischemically damaged pancreas during preservation using the two-layer (University
      of Wisconsin solution/perfluorochemical) method at 20 degrees C with thromboxane
      A2 synthesis inhibitor OKY046.
AB  - We have shown that 5-hr preservation using the two-layer (University of Wisconsin
      solution/perfluorochemical) method at 20 degrees C allows ATP synthesis and makes
      it possible to resuscitate a canine pancreas subjected to 90 min of warm
      ischemia. However, 8 hr of preservation using this method caused a disturbance of
      vascular microcirculation and did not resuscitate the grafts. The aim of this
      study was to examine the effect of thromboxane A2 synthesis inhibitor OKY046 on
      vascular endothelial cells and ATP tissue levels of canine pancreas during
      preservation using the two-layer (University of Wisconsin
      solution/perfluorochemical) method at 20 degrees C, and vascular microcirculation
      and pancreas viability after transplantation. Graft viability was judged by graft
      survival following autotransplantation. ATP tissue levels were measured by high
      performance liquid chromatography at the end of preservation. Viability of the
      vascular endothelial cells was judged using nuclear trypan blue uptake of the
      graft after preservation. Pancreatic tissue perfusion was measured using an H2
      clearance technique after reperfusion. Pancreas grafts subjected to 90 min of
      warm ischemia were not viable (0/5). However, 5-hr preservation made it possible
      to recover the pancreas (5/5); 8-hr preservation was not successful (0/3). ATP
      tissue levels after 5-hr and 8-hr preservation were 9.40+/-2.09 and 7.37+/-1.06
      micromol/g dry weight, respectively, and OKY046 did not affect ATP synthesis
      during 8-hr preservation (8.44+/-0.92 micromol/g dry weight). The percentage of
      nuclear trypan blue uptake of endothelial cells in 8-hr-preserved grafts was
      37.6+/-11.6% and was significantly higher than the value in 5-hr-preserved grafts
      (5.0+/-3.0%; P<0.01). However, OKY046 significantly reduced trypan blue uptake in
      8-hr-preserved grafts (8.2+/-3.6%; P<0.01). Pancreatic tissue perfusion in 8-hr
      preserved grafts after 2 hr of reperfusion was 28.5+/-7.5 ml/min/100 g, and was
      significantly lower than the value in 5-hr-preserved grafts (57.1+/-4.4 ml/
      min/100 g; P<0.01), but OKY046 dramatically improved pancreatic tissue perfusion
      (97.1+/-14.6 ml/min/100 g; P<0.01). As a consequence, 8-hr-preserved grafts were
      resuscitated (4/5). We conclude that OKY046 protects the vascular endothelium
      during preservation by the two-layer method at 20 degrees C and consequently
      improves vascular microcirculation on reperfusion. Together with ATP synthesis,
      which is essential for repairing damaged cells, the canine pancreas graft
      subjected to 90 min of warm ischemia is resuscitated during 8-hr preservation by
      the two-layer method at 20 degrees C. This method holds promise for pancreas
      kidney transplantation from cardiac arrest donors.

PMID- 8878379
TI  - Factors influencing the adequacy of microencapsulation of rat pancreatic islets.
AB  - The observation that only a portion of all alginate-polylysine microcapsules are
      overgrown after implantation suggests that physical imperfections of individual
      capsules, rather than the chemical composition of the material applied, are
      responsible for inducing insufficient biocompatibility and thereby fibrotic
      overgrowth of those capsules. We recently developed a lectin binding assay that
      allows for quantifying the portion of inadequately encapsulated islets, and
      demonstrated that inadequately encapsulated islets induce a fibrotic response
      associated with graft failure. The present study investigates factors influencing
      the adequacy of encapsulation of pancreatic islets. We applied our lectin binding
      assay and found that the number of inadequate, and particularly incomplete,
      capsules is influenced by the following factors. (1) A capsule diameter of 800
      micrometers is associated with a lower percentage of inadequate capsules than
      smaller (500 micrometers and 600 micrometers) or larger (1800 micrometers)
      capsules. (2) A high rather than low guluronic acid content of the alginate is
      associated with a lower percentage of inadequate capsules. This can be explained,
      at least in part, by smaller ranges of swelling and subsequent shrinkage during
      the encapsulation procedure. (3) An increase in viscosity caused by applying a
      higher alginate concentration compensates for a low guluronic acid content. This
      effect of increased viscosity cannot be explained by a reduced range of swelling
      and shrinkage during the encapsulation procedure. We conclude that alginates with
      a high guluronic acid content and a viscosity near the filtration limit are
      preferable in order to minimize the number of inadequate capsules.

PMID- 8878380
TI  - Association between capsule diameter, adequacy of encapsulation, and survival of
      microencapsulated rat islet allografts.
AB  - As a consequence of its large volume, a microencapsulated islet graft can be
      implanted only into the peritoneal cavity. The graft volume can be reduced by
      using small capsules. However, reduction of the diameter of the capsules holds a
      certain risk, because with smaller capsules, more islets may be found to protrude
      from the capsules. We have developed a lectin binding assay which, after
      encapsulation, specifically labels islets or parts of islets that are
      insufficiently immunoprotected as a consequence of inadequate, and particularly
      incomplete, encapsulation. With this assay, we found that a reduction of the
      capsule diameter from 800 micrometers to 500 micrometers was associated with an
      increase in the percentage of inadequately encapsulated islets from 6.3+/-1.2% to
      24.2+/-1.5%. The in vivo significance of this finding was investigated by
      performing allotransplantations with large diameter (700-800 micrometers) and
      small diameter (400-500 micrometers) capsules. With large-capsule islet grafts,
      all recipients (n=5) became normoglycemic for 7-16 weeks, whereas with small
      capsule islet grafts, only one of seven recipients became normoglycemic. The in
      vivo significance of inadequate encapsulation was further substantiated by our
      finding that most large capsules were floating freely in the peritoneal cavity
      without any cell adhesion, whereas the vast majority of small capsules was found
      to be adherent to the surface of intra-abdominal organs and infiltrated by immune
      cell elements characteristic of both an allograft reaction and a foreign body
      reaction. We conclude that successful use of capsules with small diameters
      requires further study to determine which factors in the encapsulation procedure
      should be modified to reduce the number of inadequate small capsules.

PMID- 8878381
TI  - An open-label, concentration-ranging trial of FK506 in primary kidney
      transplantation: a report of the United States Multicenter FK506 Kidney
      Transplant Group.
AB  - This was a multicenter, open-label, concentration-ranging trial of FK506 and
      cyclosporine in 120 patients undergoing primary cadaveric kidney transplant.
      Patients were randomized to a cyclosporine-based regimen or to one of three FK506
      based regimens designed to achieve low (5-14 ng/ml), medium (15-25 ng/ml), or
      high (26-40 ng/ml) trough whole blood levels. Corresponding initial doses of
      FK506 were 0.2, 0.3, and 0.4 mg/kg/day. Patients were evaluated at 42 days after
      transplant for the occurrence of the first episode of acute rejection or
      toxicity, necessitating a dosage reduction. There was no significant difference
      among the three FK506-based regimens and the cyclosporine-based regimen for
      rejection or toxicity at 42 days. However, the incidence of acute rejection was
      significantly lower (14% for FK506 and 32% for cyclosporine; P=0.048) for the
      aggregate of all FK506-treated patients versus cyclosporine. The incidence of
      neurotoxic and gastrointestinal events was higher among FK506-treated patients
      during the first month after transplant. A significant trend was observed for
      increasing toxicity with increasing maximum trough FK506 concentrations (P=0.01)
      and for decreasing rates of rejection with increasing minimum trough FK506
      concentrations (P=0.021). FK506 was effective in preventing early rejection in
      kidney transplant recipients. The target range of whole blood levels that
      optimizes efficacy and minimizes toxicity seems to be 5-15 ng/ml. The
      corresponding recommended initial dose of FK506 for kidney transplant recipients
      seems to be 0.2 mg/kg/day.

PMID- 8878382
TI  - Tacrolimus therapy for refractory acute renal allograft rejection: definition of
      the histologic response by protocol biopsies.
AB  - Protocol biopsies were performed to define the histologic response to tacrolimus
      therapy in patients with refractory acute renal allograft rejection. Renal
      allograft biopsies were performed at defined intervals after initiation of
      tacrolimus therapy. Protocol biopsies were performed before tacrolimus therapy
      (within 48 hr of initiation of therapy) and after 1 week of therapy. If the 1
      week biopsy did not show rejection reversal, repeat protocol biopsies were
      obtained at 1- to 2-week intervals, until histologic reversal was observed.
      Additional biopsies were obtained at 4 weeks and at 8-12 weeks after initiation
      of tacrolimus therapy. Indicated biopsies were also performed to evaluate
      increases in serum creatinine. A total of 92 biopsies were performed in 23
      patients (average 4.0 biopsies/ patient). Biopsies were performed in each patient
      immediately before starting tacrolimus therapy (23 biopsies), and 69 biopsies
      (3.0 biopsies/patient) were performed during tacrolimus therapy. Rejection
      diagnosis was based on strict Banff criteria. Pretacrolimus biopsies demonstrated
      mild acute rejection in 64% of patients and moderate acute rejection in 36%. One
      week after initiation of tacrolimus therapy, protocol biopsies revealed the
      following: no rejection (60%), improvement (13%), no change (20%), and worsening
      rejection (7%). Histologic changes at 1 week did not correlate with changes in
      renal function, as 63% of patients that showed histologic improvement or reversal
      during the first 2 weeks of therapy did not show improvement in serum creatinine.
      A lack of histologic improvement (or worsening) at 1 week was demonstrated in a
      significant proportion of patients (27%); increased tacrolimus dosing provided
      rejection reversal or improvement in 1-2 weeks in each of these patients.
      Recurrent rejection was diagnosed on eight biopsies in seven patients, however
      six episodes were diagnosed by protocol biopsies alone (i.e., in the absence of
      an elevation in serum creatinine). Delayed improvement in renal function, despite
      histologic reversal, was likely due to physiologic effects of tacrolimus (i.e.,
      afferent arteriolar vasoconstriction), as histologic evidence of tacrolimus
      toxicity was not observed during the first 2 weeks of therapy. Histologic
      evidence of tacrolimus nephrotoxicity (nodular arteriolar hyalinosis) was found
      in 21% (15 of 69) of biopsies in 39% of patients (9 of 23) at a median time of 60
      days (range 12-150 days). Tacrolimus dose and blood levels (by IMx assay) did not
      correlate with development of clinically silent or clinically evident
      nephrotoxicity. IN CONCLUSION: 1) protocol biopsies provide information that
      allows individualization of tacrolimus rejection therapy, 2) histologic
      resolution of rejection often precedes biochemical improvement, 3) histologic
      evidence of tacrolimus nephrotoxicity is seldom observed in the first 2 weeks of
      therapy, and 4) clinically silent recurrent rejection and clinically silent
      tacrolimus nephrotoxicity are observed with significant frequency during
      tacrolimus therapy for refractory renal allograft rejection.

PMID- 8878383
TI  - Expression of cytokine messenger RNA after heart transplantation: relationship
      with rejection and serum cytokines.
AB  - Different groups of cytokines may initiate or inhibit the rejection process. We
      used the polymerase chain reaction to study the expression of cytokine mRNA for
      interleukin (IL)-2, -4, -6 and -10, tumor necrosis factor-alpha, and interferon
      gamma in 187 biopsy specimens from 24 human cardiac transplant recipients 5-555
      days after transplantation. Cytokine levels in the serum were also measured.
      Cytokine mRNA was detected in 38.5% of biopsy specimens. IL-10 mRNA was detected
      more frequently with mild or absent rejection (11.6% in grades 0 and 1 - vs. 1.4%
      in grades 2 and 3, P=0.01). Up to 90 days after transplantation, IL-2 mRNA was
      detected more frequently with moderate rejection (13% in grades 2 and 3 vs. 0% in
      grades 0 and 1, P=0.076), and IL-4 mRNA was detected more frequently with mild or
      absent rejection (16% in grades 0 and 1 - vs. 0% in grades 2 and 3, P=0.061).
      More than 90 days after transplantation, IL-2 mRNA was detected more frequently
      with mild or absent rejection (10% in grades 0 and 1 vs. 0% in grades 2 and 3,
      P=0.078). Serum IL-4 levels corresponding to biopsy specimens positive for IL-4
      mRNA were higher than those corresponding to specimens negative for IL-4 mRNA (59
      pg/ml vs. 32 pg/ml medians, P=0.028). Our results suggest that IL-10 and possibly
      IL-4 (T helper 2 cytokines) may suppress graft rejection, whereas IL-2 (T helper
      1 cytokine) may promote cellular rejection. In addition, cytokine profiles may
      change with length of time after transplantation. The association of elevated
      serum levels of IL-4 with increased expression of intragraft IL-4 mRNA may
      suggest release of this cytokine from the graft into the circulation.

PMID- 8878384
TI  - Neutrophil elastase: a determinant of endothelial damage and reperfusion injury
      after liver transplantation?
AB  - Reperfusion injury has been implicated in the development of primary graft
      dysfunction (PGD) after liver transplantation. Neutrophil migration and
      activation may be involved in the pathogenesis of this injury. We studied
      neutrophil activation and its role in the etiology of PGD by measuring neutrophil
      elastase by radioimmunoassay, in serial blood samples of 19 patients before,
      during, and for 24 hr after transplantation. In a subgroup of patients, we also
      measured soluble thrombomodulin at the same time points as a marker of
      endothelial damage. The pretransplant elastase level was significantly raised
      (40.13+/-4.84 ng/ml, mean+/-SEM) compared with levels of healthy controls (18.7+/
      5.6 ng/ml, P<0.05). A marked increase in elastase activity followed reperfusion,
      with a peak at 2 hr (370+/-50.5 ng/ml, P<0.01). Thereafter, there was a decline,
      but elastase remained elevated at 24 hr (186+/-60.94 ng/ml). The mean increase in
      neutrophil elastase after reperfusion correlated significantly with markers of
      graft function (P<0.05) and with the mean rise in soluble thrombomodulin
      (P=0.042), which increased from a pretransplant level of 81.2+/-11.32 to 186+/
      50.4 ng/ml, 6 hr after reperfusion (P<0.05). The results of this study indicate
      that marked neutrophil activation and endothelial cell damage occurs after graft
      reperfusion during orthotopic liver transplantation, and the degree of activation
      correlates with markers of graft function, which may suggest a role in the
      etiology of PGD.

PMID- 8878385
TI  - Relationship of FK506 whole blood concentrations and efficacy and toxicity after
      liver and kidney transplantation.
AB  - FK506 (tacrolimus) is a safe and effective immunosuppressant for the prevention
      of organ rejection after organ transplantation. FK506 has a relatively narrow
      therapeutic index and the correlation of dose to blood concentration is poor as a
      result of moderate variability in pharmacokinetic parameters between patients.
      Therapeutic monitoring of whole blood FK506 drug concentrations has been used in
      an effort to determine whether a relationship exists between concentrations of
      FK506 in the blood and the development of toxicity or the risk for organ
      rejection. An analysis of the relationship between FK506 blood levels and the
      occurrence of toxicity and rejection was carried out using data from four recent
      clinical trials. Trough FK506 levels within a 7-day window before the onset of
      rejection or toxicity were analyzed using logistic regression models. In kidney
      transplant patients (n=92), a significant correlation between FK506 levels and
      the incidence of both toxicity (P=0.01) and rejection (P=0.02) was seen. In liver
      transplant patients from three clinical trials, FK506 levels correlated well with
      the incidence of toxicity (P < or = 0.01); however, there was no significant
      relationship between FK506 levels and the incidence of rejection. It is concluded
      that therapeutic monitoring of whole blood FK506 levels may be useful for
      minimizing the risks of both toxicity and rejection in kidney transplant patients
      and for minimizing the risk of toxicity in liver transplant recipients.

PMID- 8878386
TI  - Risk factors of invasive Candida and non-Candida fungal infections after liver
      transplantation.
AB  - Fungal infections are associated with a high mortality rate after liver
      transplantation. To describe risk factors for fungal infections, 405 consecutive
      liver transplant recipients were analyzed. Forty-five patients (11%) developed
      invasive fungal infection. Median posttransplantation time to the first episode
      was 60 days. Pathogens were Candida species (spp) (n=24, 53%), Cryptococcus
      neoformans (n=10, 22%), Aspergillus spp (n=6, 13%), Rhizopus spp (n=l), and
      others (n=4). Presentations of infection included disseminated (n=9), intra
      abdominal (n=9), esophageal (n=9), lung (n=8), blood (n=6), and central nervous
      system infections (n=3), and sinusitis with esophagitis (n=1). Eighteen patients
      (40%) with invasive fungal infection died, and 13 (72%) of these deaths were
      attributable to fungi. Mortality in the nonfungal infection group was 12%.
      Univariate analysis identified separate risk factors for Candida (intra-abdominal
      bleeding), Aspergillus (fulminant hepatitis), and cryptococcal (symptomatic
      cytomegalovirus infection) infections. In both univariate and multivariate
      analyses, a high intratransplant transfusion requirement and posttransplant
      bacterial infection were identified as significant risk factors for all types of
      fungal infection. The risk factor analysis reported here suggests that different
      pathogenic processes lead to Candida and non-Candida infection in liver
      transplant recipients. Their identification should prompt specific prophylactic
      measures to reduce morbidity and mortality in this population.

PMID- 8878387
TI  - Hyperlipidemia after liver transplantation: natural history and treatment with
      the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin.
AB  - This study was designed to determine the frequency of hyperlipidemia after
      orthotopic liver transplantation and whether treatment with a hydroxy
      methylglutaryl coenzyme A reductase inhibitor was safe and efficacious.
      Cholesterol levels were assessed in 45 consecutive adult liver transplants (mean
      +/- SE). Four of 22 patients on cyclosporine (CsA) (18%) and three of 23 patients
      on FK506 (13%) had levels >225 mg/dl at 12 months (cholesterol levels for
      patients on CsA [total n=22]: pre-Tx = 140+/-11, 1 month = 183+/-36,3 months =
      221+/-12, 6 months = 211+/-11, 12 months = 202+/-14 [P<0.01 vs. pre-Tx]; FK506
      [total n=23]: Pre-Tx = 151+/-13, 1 month = 187+/-22, 3 months = 188+/-10, 6
      months = 184+/-13, 12 months = 164+/-9 [P=0.02 vs. CsA]). A separate cohort of
      patients with stable graft function, cholesterol >225 mg/dl, and two additional
      risk factors for coronary artery disease were started on pravastatin. Ninety
      eight patients were enrolled. Sixteen patients (16%) discontinued the drug
      because of subjective complaints. No episodes of rhabdomyolysis or hepatotoxicity
      occurred (cholesterol levels for patients on CsA [total n=65]: pretreatment =
      251+/-7, 6 months = 220+/-7 [P=0.01 vs. pretreatment], 12 months = 224+/-8
      [P=0.01 vs. pretreatment]; FK506 [total n=17]: pretreatment = 251+/-17, 6 months
      = 219+/-17, 12 months = 208+/-17 [P=0.08 vs. pretreatment]). Natural killer cells
      isolated from normal volunteers (n=14) exhibited 27+/-9% specific lysis. Patients
      on FK506 or cyclosporine-based immunosuppression alone (n=11) exhibited 20+/-4%
      specific lysis. Standard immunosuppression plus pravastatin (n=10) decreased
      lysis to 0.2+/-10% (P<0.02 vs. controls and standard immunosuppression). We
      conclude: (1) posttransplant hyperlipidemia occurs less frequently in liver
      transplant patients than in renal or cardiac transplants; (2) pravastatin is safe
      and efficacious for cholesterol reduction in liver transplant patients; and (3)
      pravastatin coadministered with standard immunosuppression reduces natural killer
      cell-specific lysis in these recipients.

PMID- 8878388
TI  - Factors associated with postoperative respiratory complications in pediatric
      liver transplantation from living-related donors.
AB  - Factors associated with respiratory complications (RCs) after pediatric living
      related liver transplantation were statistically analyzed in the first 100 cases
      where surgery was performed at Kyoto University. The overall incidence of
      postoperative RCs was 45%, including atelectasis (23%), pleural effusion (23%),
      and pneumonia (12%). Univariate and multivariate analyses were performed with
      regard to the association between postoperative RCs and 13 pre- and
      intraoperative variables that were considered to represent the preoperative
      medical status of the patients and the severity of operative insult. The
      following four independent variables were found to have prognostic significance
      with regard to the postoperative RCs: (1) history of preoperative RCs, (2) height
      < or = -2 SD from the mean for the age, (3) United Network for Organ Sharing
      score = 1, and (4) intraoperative blood loss > or = 20% of body weight.
      Postoperative death was highly affected by postoperative RCs: 8 of 11 deaths
      during the study period were directly or closely related to postoperative RCs. We
      conclude that postoperative RCs are major contributing factors to operative
      morbidity and mortality in pediatric living-related liver transplantation, which
      may possibly be reduced by intensive respiratory management of patients with the
      above risk factors for postoperative RCs.

PMID- 8878389
TI  - Serum levels of cytokines and secondary messages after T-cell-depleted and non-T
      cell-depleted bone marrow transplantation: influence of conditioning and
      hematopoietic reconstitution.
AB  - Cytokines are increasingly recognized as important mediators of graft-versus-host
      disease (GVHD). Measurements of cytokine serum levels in patients with GVHD, and
      successful prevention and treatment of the disease with the use of cytokine
      antagonists to either the cytokine or its receptor, are only two of several
      factors demonstrating the involvement of cytokines in GVHD. To further
      investigate the role of cytokines in the pathomechanism of acute GVHD, we
      investigated endogenous serum levels of various cytokines and dependent molecules
      in sera of 14 patients after T-cell-depleted (TCD) bone marrow transplantation
      (BMT) and compared the results with those of 12 patients undergoing non-TCD BMT.
      The effect of various conditioning regimens and of hematopoietic reconstitution
      on cytokine serum levels was analyzed in detail in these cohorts of patients by
      measuring interferon (IFN)-gamma, IFN-alpha, tumor necrosis factor-alpha,
      interleukin-6, neopterin, and beta2-microglobulin. The analyses showed that an
      increase in IFN-gamma and neopterin serum levels was a specific feature of
      cyclophosphamide administration and was not observed after other cytostatic drugs
      or total body irradiation, and that an increase in IFN-gamma, neopterin, beta2
      microglobulin, and IFN-alpha release depends on the presence of T cells in the
      graft. We conclude that significant cytokine serum alterations were noted after
      TCD BMT as compared with after non-TCD BMT. These alterations, besides depletion
      of cytotoxic effector cells, might be involved in preventing GVHD after TCD BMT.
      In addition, more attention should be devoted to the cytokine release-inducing
      capacity of the conditioning regimen, because such a release might influence the
      occurrence of transplant-related complications after BMT.

PMID- 8878390
TI  - Alloreactive anti-HLA-B7 cytolytic T cell clones use restricted T cell receptor
      genes.
AB  - Most alloreactive T cells specifically recognize peptides bound to donor MHC
      molecules. In addition to peptides, solvent accessible MHC residues also may
      stimulate alloreactive T cells. We studied T cell receptor (TCR) usage by 16
      independent anti-HLA-B7 alloreactive cytolytic T lymphocyte (CTL) clones. Most or
      all of these CTL clones recognized unique peptides bound to HLA-B7. Despite the
      diversity of peptides recognized, 11 out of 15 CTL clones analyzed expressed TCR
      V(alpha) gene segment (AV) subgroups 1 and 3. Within AV subgroup 1, four of six
      clones expressed AV2; within AV subgroup 3, three clones used AV6. Ten of 14 CTL
      clones analyzed expressed V(beta) gene segment (BV) subgroups 4 and 1. In
      subgroup 4, BV14 was expressed by four of five alloreactive CTL clones. Similar
      AV and BV usage restriction was not found in mitogen-stimulated peripheral blood
      T cells from the major donor of the CTL clones. TCR A and TCR B junctional region
      sequences were quite diverse in length and sequence, although two CTL clones
      expressed nearly identical TCR B chains. We found no correlation between TCR AV
      or TCR BV usage and CTL recognition of 81 HLA-B7 variants. These results are
      consistent with models of TCR structure, in which very diverse TCR CDR3 regions
      contact very diverse peptides, and moderately diverse TCR CDR1 and CDR2 regions
      contact moderately diverse MHC alpha-helices.

PMID- 8878391
TI  - Immunosuppression with monoclonal antibodies and CTLA4-Ig after myoblast
      transplantation in mice.
AB  - Various combinations of monoclonal antibodies specific for lymphocyte cell
      surface antigens and a recombinant molecule (CTLA4-Ig) were used to
      immunosuppress mice after transplantation of MHC-incompatible myoblasts. To
      assess the effectiveness of the immunosuppression, the donor myoblasts were
      obtained from a transgenic mouse (TnI LacZ1/29) containing a beta-galactosidase
      (beta-gal) reporter gene under the control of a muscle-specific promoter. No
      muscle fibers expressing beta-gal were observed 1 month after the myoblast
      transplantation, when the animals were not immunosuppressed or were treated with
      CTLA4-Ig alone. Approximately 50% of the muscle fibers expressed the beta-gal
      reporter gene 1 month after transplantation in mice treated with CTLA4-Ig
      combined with an anti-CD4 monoclonal antibody and in mice treated with a
      combination of anti-CD4, anti-CD8, and anti-lymphocyte function-associated
      antigen-1. The percentage of beta-gal-labeled muscle fibers increased to 94% when
      this combination of the three monoclonal antibodies was administrated weekly for
      3 weeks. Although excellent graft survival rates were obtained 1 month after
      transplantation, reflecting an effective immunosuppression by these three
      treatments, no beta-gal-positive fibers were found 2 months after the
      transplantation, indicating the inability of these immunosuppressive agents to
      maintain long-term graft survival and induce tolerance to the myoblasts and
      muscle fibers of donor origin.

PMID- 8878392
TI  - Adenoviral-mediated overexpression of I(kappa)B(alpha) in endothelial cells
      inhibits natural killer cell-mediated endothelial cell activation.
AB  - Activated natural killer (NK) cells have been found in rejecting discordant
      xenografts and may contribute to endothelial cell (EC) activation and damage. The
      transcription of genes associated with EC activation, such as E-selectin and
      interleukin (IL)-8, is regulated by the transcription factor NF-kappaB. In
      resting EC, NF-kappaB is complexed within the cytoplasm to I(kappa)B(alpha), and
      EC activation leads to dissociation of the I(kappa)B(alpha)-NF-kappaB complex and
      nuclear translocation of NF-kappaB. We investigated whether overexpression of
      I(kappa)B(alpha) in EC, using adenoviral gene transfer, could block NF-kappaB
      translocation, thereby inhibiting NK cell-mediated EC activation. Co-culture of
      human NK cells with porcine EC resulted in a threefold increase in E-selectin
      expression after 4 hr and secretion of greater than 650 pg/ml porcine IL-8 over
      24 hr. Overexpression of I(kappa)B(alpha) inhibited the NK cell-mediated
      induction of E-selectin expression and IL-8 secretion, whereas overexpression of
      P-galactosidase did not. The inhibition of EC activation was not due to variation
      in NK-EC adhesion, as the level of adhesion was similar between adenovirally
      infected and noninfected EC over 4 hr. The level of NK cell-mediated EC
      cytotoxicity was not significantly different after 4 hr of co-culture, but after
      24 hr, cytotoxicity was increased in virally infected cells. Cytotoxicity was
      more marked in cells overexpressing I(kappa)B(alpha) than cells overexpressing
      beta-galactosidase. SLA class I and the induction of SLA class II antigen in
      response to interferon-gamma treatment were reduced in cells infected with adeno
      I(kappa)B(alpha) and empty adenovirus, demonstrating that viral infection alone
      can influence EC biology. Overexpression of I(kappa)B(alpha) using adenovirus
      provides a novel approach to inhibiting NK cell-mediated EC activation, but
      additional strategies will be required to inhibit NK cell-mediated cytotoxicity.

PMID- 8878393
TI  - In vivo modulation of CD26 (dipeptidyl peptidase IV) in the mouse: effects of
      polyreactive and monoreactive antibodies.
AB  - We previously reported that intravenous injections in rabbits or guinea pigs of
      divalent antibodies to purified protein or carbohydrate antigens located mainly
      on endothelial cells induce acute pulmonary edema, which is often lethal.
      Surviving animals develop resistance to the injurious effect of subsequent
      injection of antibodies (adaptation), associated with shedding of antigen
      antibody complexes from endothelial cells. In the present study, we investigated
      and compared in mice the effects of 3-day multiple injections of two different
      rabbit antibody (IgG) preparations against antigens expressed mainly at the
      surface of epithelial cells. The first preparation contained antibodies to a
      single transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV])
      (monoreactive anti-DPP IV IgG); the second contained antibodies against multiple
      antigens of the renal tubular brush border (BB), including DPP IV (polyreactive
      anti-BB IgG). Both IgG preparations caused loss of DPP IV from the organs
      studied, as shown by reduction in enzyme activity in tissue homogenates and by
      immunofluorescence microscopy, which showed loss of DPP IV from cell surface.
      However, the monoreactive anti-DPP IV IgG induced considerably greater reduction
      than polyreactive anti-BB IgG. Loss of DPP IV from the cell surface probably
      occurred by shedding of immune complexes into vascular and extravascular fluids,
      including bile and urine. The results may have relevance to hyperacute rejection
      of xenografts, as from pigs to primates. Since human natural antibodies that bind
      to porcine cells are polyreactive, a new prophylactic strategy for hyperacute
      rejection might be based on down-regulation of the major xenogeneic antigen,
      alpha-galactosyl, by injecting donor animals with monoreactive alpha-galactosyl
      antibodies before transplantation.

PMID- 8878394
TI  - Effects of the pharmacokinetic interaction between orally administered sirolimus
      and cyclosporine on the synergistic prolongation of heart allograft survival in
      rats.
AB  - Oral administration, but not continuous intravenous infusion, of sirolimus (SRL)
      in combination with cyclosporine (CsA) produces a pharmacokinetic interaction,
      namely increases in the whole blood trough concentrations of SRL ([SRL(WB)]) and
      CsA ([CsA(WB)]). The effects of this pharmacokinetic interaction on the synergism
      between SRL and CsA was examined in Wistar Furth (RT1u) recipients of Buffalo
      (RT1b) heart allografts. A 14-day course of oral SRL produced dose-dependent
      prolongation of heart allografts: in untreated controls, 0.5 mg/kg SRL per day
      extended the mean survival time (MST) from 6.4+/-0.5 days to 12.3+/-3.8 days
      (P<0.05); SRL at 1.0 mg/kg per day prolonged the MST to 18.0+/-5.5 days (P<0.01);
      at 2.0 mg/kg SRL per day, MST was extended to 52.5+/-13.2 days (P<0.01); and 4.0
      mg/kg SRL per day prolonged MST to 90.0+/-41.1 days (P<0.01). Comparison of the
      in vivo effects after oral versus continuous intravenous SRL administration
      suggested that the oral bioavailability of SRL is less than 10%. Combinations of
      oral SRL and CsA synergistically prolonged heart allograft survival, as
      documented by combination index values of 0.01-0.64 (combination index <1
      indicates synergistic interaction). In rats treated with dual drug combinations,
      CsA increased the bioavailability of SRL by two- to elevenfold, and SRL increased
      the bioavailability of CsA by two- to threefold, thereby significantly decreasing
      the oral effective dose (ED) values for each drug. The ED50 for SRL alone is 2.4
      mg/kg per day, which produces an average [SRL(WB)] of 13.2 ng/ml. The ED50 for
      CsA alone is 8.0 mg/kg per day, which produces an average [CsA(WB)] of 1642
      ng/ml. However, when the two drugs are combined, the ED50 effect is achieved with
      only 0.34 mg/kg SRL per day ([SRL(WB)]=1.1 ng/ml) and 2.1 mg/kg CsA per day
      ([CsA(WB)] =326 ng/ml). Individually, 0.34 mg/kg SRL per day produces an ED9 with
      an average [SRL(WB)] of 0.6 ng/ml, and 2.1 mg/kg CsA per day produces an ED22
      with an average [CsA(WB)] of 174 ng/ml. Thus, the pharmacokinetic interaction
      between oral SRL and CsA contributes to the in vivo synergism between the two
      drugs.

PMID- 8878395
TI  - Effect of in vivo rapamycin treatment on de novo T-cell development in relation
      to induction of autoimmune-like immunopathology in the rat.
AB  - Cyclosporine (CsA) and FK506 are structurally unrelated immunosuppressants, but
      function in similar ways. FK506 and rapamycin (RAPA), on the other hand, have
      structural similarities, but act by different mechanisms to yield
      immunosuppression. Besides their immunosuppressive action, CsA and FK506 are
      known to interfere with T-cell development. CsA treatment after lethal X
      irradiation and syngeneic bone marrow transplantation results in autoimmune
      disease, which is referred to as CsA-induced autoimmunity. In this study, we
      examined the effect of RAPA on T-cell development by flow cytometry and
      immunohistochemistry in female Lewis and Brown Norway rats. Irradiation and
      syngeneic bone marrow transplantation were performed before a 4-week course of
      RAPA administration to determine de novo T-cell development in relation to
      possible autoimmune phenomena. RAPA interfered with the maturation of thymocytes
      to the CD4+CD8+ DP stage, which resulted in a relative increase in TCRalphabeta(
      ) immature thymocytes, localized in a rim along the outer cortex. The thymus of
      RAPA-treated animals had a thinner cortex, leading to stronger thymic atrophy. In
      the periphery, only a few T cells were observed at the end of RAPA treatment. In
      the Lewis rat, a normal CD4/CD8 T-cell ratio and an increased Th1/Th2 ratio was
      observed within the T-cell population. Six weeks after cessation of RAPA therapy,
      the T-cell compartment was restored to normal, with respect to number and
      phenotype. In Brown Norway rats, however, T-cell areas were barely detectable at
      the end of RAPA treatment. The CD4/CD8 T-cell ratio was decreased as a result of
      a lower number of CD4 T cells; the Th1/Th2 ratio was increased but Th2 remained
      higher. Similar to Lewis rats, the situation was almost normalized 6 weeks after
      cessation of RAPA administration. However, Brown Norway rats, in contrast to
      Lewis rats, showed T-cell infiltration and concomitant induction of MHC class II
      in the submandibular salivary gland, as well as insulitis, in the pancreas.
      Possible relationships to Sjogren's disease and diabetes remain to be
      established.

PMID- 8878396
TI  - Induction of transplantation tolerance by chimeric donor/recipient class I RT1.Aa
      molecules.
AB  - Donor-specific transplantation tolerance was induced by administration of
      chimeric antigens in which four donor immunogenic amino acids (a.a.) were
      substituted onto the host class I MHC protein. We constructed chimeric rat RT1.Aa
      cDNA molecules by substituting nucleotides in the alpha1 helical region that
      encode 10 Lewis (LEW; RT1.A1) a.a., namely Asp58, Arg62, Glu63, Gln65, Lys66,
      Gly69, Asn70, Asn73, Ser77, and Asn80 ([alpha(1h)1]-RT1.Aa). The chimeric
      [alpha(1h)1]-RT1.Aa cDNA sequence was verified before transfection into Buffalo
      (BUF; RT1b) hepatoma cells. Interestingly, the helical regions of LEW rats
      (alpha(1h)1) and Wistar Furth (WF; RT1u) rats (alpha(1h)u) share four a.a.
      (Arg62, Glu63, Gln65, and Gly69). Consequently, subcutaneous administration of
      [alpha(1)1]-RT1.Aa transfectants (20x10(6); day -7) immunized BUF rats to reject
      in rapid fashion either LEW heart allografts (mean survival time [MST] = 4.2+/
      0.4 days vs. 5.6+/-0.5 days in controls; P<0.001) or WF heart allografts
      (MST=4.4+/-0.6 days vs. 6.0+/-0.0 days in controls; P<0.002). Subcutaneous
      immunization of ACI (RT1a) rats with [a(1)1]-RT1.Aa transfectants (bearing 10 LEW
      donor a.a.) accelerated the rejection of LEW hearts (MST=5.0+/-0.8 days vs. 8.2+/
      0.4 days in controls; P<0.001). In contrast, the same [a(1)1]-RT1.Aa
      transfectants (bearing only four WF donor a.a.) injected subcutaneously into ACI
      rats modestly prolonged the survival of WF hearts to 14.0+/-10.3 days from 5.4+/
      0.5 days in controls (P<0.001). Furthermore, ACI recipients were rendered
      tolerant to WF heart allografts by a single injection via the portal vein of
      soluble [a(1)1]-RT1.Aa (but not RT1.Aa, RT1.Au, or [a(2)1]-RT1.Aa) antigens in
      conjunction with brief oral gavage treatment with cyclosporine. Thus, selected
      donor immunogenic a.a. (Arg62, Glu63, Gln65, and Gly69) of class I MHC antigens
      become tolerogenic when flanked by host sequences.

PMID- 8878397
TI  - Blockade of multiple costimulatory receptors induces hyporesponsiveness:
      inhibition of CD2 plus CD28 pathways.
AB  - T-lymphocyte activation requires engagement of the T cell receptor with antigen
      major histocompatibility complex, and simultaneous ligation of costimulatory
      pathways via the lymphocyte receptors CD2 and CD28/ CTLA4. Anti-CD2 monoclonal
      antibody (mAb) blocks the interaction of the antigen-presenting cell receptor
      CD48 with its ligand CD2, whereas CTLA4Ig binds with high affinity to the antigen
      presenting cell ligands B7-1 and B7-2, blocking their interaction with
      CD28/CTLA4. We tested the immunosuppressive effects of simultaneously blocking
      both costimulatory pathways. Using donor C57BL/6J (H2b) hearts transplanted to
      CBA/J (H2k) recipients, anti-CD2 mAb plus CTLA4Ig administered at the time of
      transplantation prolonged cardiac allograft mean survival time to >120 days
      compared with untreated controls (12.2+/-0.5 days, P<0.01), anti-CD2 mAb alone
      (24.8+/-1.0 days, P<0.01), or CTLA4Ig alone (55.0+/-2.0 days, P<0.01).
      Retransplantation of these recipients with donor-specific and third-party grafts
      demonstrated that hyporesponsiveness and tolerance were achieved. In vitro
      stimulation of lymphocytes from tolerant recipients with donor-specific
      alloantigen resulted in normal cytotoxic T lymphocyte and mixed lymphocyte
      reaction responses, showing that clonal deletion or anergy did not occur, but
      that graft adaptation or suppression likely helped to maintain long-term graft
      survival. In vitro combinations of anti-CD2 mAb and CTLA4Ig suppressed the
      generation of allogeneic cytotoxic T lymphocytes (58%) and the mixed lymphocyte
      reaction (36%); CTLA4Ig was more effective in this regard and the two agents were
      not synergistic. Anti-CD2 mAb and CTLA4Ig suppressed mitogen-driven proliferation
      in differential fashions, suggesting that they affected independent signaling
      pathways. Anti-CD2 mAb and CTLA4Ig also inhibited interleukin (IL)-2, IL-4, and
      IL-2 receptor (CD25). These data indicate that anti-CD2 mAb plus CTLA4Ig induces
      hyporesponsiveness and tolerance. The mechanism is likely related to the initial
      disruption of independent pathways of T-lymphocyte activation leading to antigen
      specific long-term graft survival.

PMID- 8878398
TI  - Inhibition of complement, evoked antibody, and cellular response prevents
      rejection of pig-to-primate cardiac xenografts.
AB  - Complement (C) inhibition alone using a recombinant soluble form of complement
      receptor type 1 (sCR1) prevents hyperacute rejection but not subsequent
      irreversible accelerated acute rejection of discordant pig-to-cynomolgus monkey
      cardiac xenografts, which occurs within 1 week. To inhibit accelerated acute
      rejection, which is associated with a rise in serum xenoreactive antibody (Ab)
      and a cellular infiltrate, triple therapy with standard immunosuppressive agents
      (cyclosporine, cyclophosphamide, and steroids [CCS]) was combined with continuous
      C inhibition using sCR1. Each of two monkeys that received sCR1 + CCS showed
      minimal evidence of rejection when killed on days 21 and 32 in comparison to a
      monkey that received sCR1 + subtherapeutic CCS (rejected at 11 days) and a
      control that received CCS alone (rejected at 38 min). Prolonged xenograft
      survival was associated with low Ab levels and a minimal cellular infiltrate,
      suggesting that combined inhibition of C, xenoreactive Ab responses, and cellular
      immunity may be a useful approach in overcoming the immune barriers to discordant
      xenotransplantation.

PMID- 8878399
TI  - Emphysematous cystitis and pyelitis in a diabetic renal transplant recipient.
AB  - Emphysematous cystitis is a rare complication of urinary tract infection.
      Patients with diabetes mellitus, neurogenic bladder, bladder outlet obstruction,
      and recurrent urinary tract infection are at increased risk for the disease. We
      present a case of emphysematous cystitis and pyelitis in a diabetic renal
      transplant recipient. He was treated with antibiotics alone with complete
      clinical and radiologic resolution. The clinical course was benign, as described
      in most patients. The prognosis of emphysematous cystitis is good after early
      diagnosis and prompt treatment with appropriate antibiotics, blood glucose
      control, and adequate urinary drainage.

PMID- 8878400
TI  - Effect of pretransplant erythropoietin therapy on renal allograft outcome.
AB  - Erythropoietin (EPO) is widely used among patients with end-stage renal disease
      awaiting transplantation. Data suggest that EPO therapy may be immunomodulatory.
      The purpose of this study was to assess the effects of pretransplant EPO therapy
      on renal allograft outcome. We evaluated 120 consecutive renal transplant
      recipients to assess the effect of EPO on graft outcome following renal
      transplantation. Among the study population, 58 patients were receiving EPO
      before transplantation (EPO group) and 62 patients were not treated with EPO (non
      EPO group). Twenty-four of 58 EPO-treated patients (41%) experienced delayed
      graft function after transplantation, compared with 11 of 62 (18%) non-EPO
      treated patients (P<0.05). The incidence of acute rejection, time to first
      rejection, and 1-year graft survival rate did not differ between the two groups.
      In conclusion, pretransplant EPO therapy does not appear to adversely impact on
      the incidence of acute rejection or 1 year graft survival rate. However, EPO
      treated patients may be predisposed to the development of delayed graft function.

PMID- 8878401
TI  - Kidney transplant recipients who die with functioning grafts: serum creatinine
      level and cause of death.
AB  - How to analyze death with function (DWF) in transplant survival statistics has
      become an important issue. DWF is a predominant cause of late graft loss. We
      recognize that some deaths may be related to the transplant. However, considering
      DWF as a graft loss may obscure some analyses. An additional consideration is
      whether patients who "die with function" actually had good kidney function or
      whether their death was related to or hastened by impaired function. To answer
      this question, we studied the serum creatinine level and cause of death for
      kidney recipients who died with function. Between January 1, 1985, and December
      31, 1994, we did 1932 kidney transplants for 1806 recipients. Of these, 220 died
      with function. For the 220, we assessed the time posttransplant that death
      occurred, the serum creatinine level before the terminal event, and the cause of
      death. The most common causes of death were infection (22%), myocardial
      infarction (17%), and sudden death (15%). Mean serum creatinine levels were less
      than 2 mg/100 ml at 1 year before and at the time of death for the vast majority
      of these recipients. Our findings demonstrate that kidney recipients who die with
      function have good renal function--additional support for presenting graft
      survival data both with and without death censored.

PMID- 8878402
TI  - Induction of immunosuppression by microemulsion cyclosporine in liver
      transplantation.
AB  - Twenty-five liver transplant patients were administered liquid microemulsion
      cyclosporine (Neoral, 5 mg/kg b.i.d.) via a nasogastric tube until they could
      take oral medication. The first dose was given within 6 hr after surgery.
      Adequate trough levels of cyclosporine were obtained from the first postoperative
      day. The total exposure to the drug was low on the first postoperative day, but a
      significantly improved pharmacokinetic profile with a high maximal concentration
      and a low time to maximal concentration was found from the second postoperative
      day. The absorption from Neoral increased during the first week. After 1 week, a
      low within-patient variation coefficient for dose-adjusted cyclosporine trough
      levels was found (17%). The between-patient variation coefficient was low during
      the whole postoperative period (31%). We conclude that in liver transplant
      patients adequate immunosuppressant blood levels of cyclosporine can be obtained
      in the immediate postoperative period using Neoral without the need to go to the
      intravenous form of the drug.

PMID- 8878403
TI  - Use of polytetrafluoroethylene patch for temporary wound closure after pediatric
      liver transplantation.
AB  - Despite numerous options for pediatric transplantation, closure of the abdominal
      wall after liver transplantation is occasionally difficult, resulting in
      increased abdominal pressure and possible vascular compromise. Since 1990, we
      have utilized a 2-mm thick sheet of polytetrafluoroethylene (PTFE) to overcome
      this situation in 21 transplants for 17 patients. The median age was 0.9 months.
      Ten of the 21 transplants utilized full-size grafts. The donor to recipient
      weight ratio was 1.7+/-1.2. Cadaveric left lateral segments were used in 8 of 21
      transplants (weight ratio, 7.4+/-5.9), living donor left lateral segments were
      used in 3 of 21 transplants (weight ratio, 13.2+/-6.7). We were able to remove 14
      of 21 patches with one additional operation, whereas 4/21 patches required two
      operations and 3/21 required three operations. Reoperations identified two cases
      of hepatic artery thrombosis not previously identified by duplex ultrasonography.
      There were no technical problems or adverse effects associated with the use of
      the PTFE patch. After patch removal, the fascia was closed with a nonabsorbable
      suture and the skin was allowed to close by secondary intention. There were no
      wound infections, portal vein thrombosis, or fluid and electrolyte abnormalities.
      PTFE is a safe, temporary alternative to primary wound closure in liver
      transplantation when the size of the graft or intestinal and graft edema does not
      allow conventional closure of the abdomen. Infectious, fluid/electrolyte, or
      ventilatory complications were not noted. The necessity of a second-look
      operation is useful in assessing the graft and vascular patency. The majority of
      patches can be removed within the first postoperative week.

PMID- 8878404
TI  - De novo amyloid synthesis in ocular tissue in familial amyloidotic polyneuropathy
      after liver transplantation.

PMID- 8878405
TI  - Tacrolimus allows autoinfective development of the parasitic nematode
      Strongyloides stercoralis.

PMID- 8878406
TI  - Human ovarian tumour cells can bind hyaluronic acid via membrane CD44: a possible
      step in peritoneal metastasis.
AB  - Our previous studies have suggested that the interaction between hyaluronic acid
      (HA) on peritoneal mesothelial cells and the membrane adhesion molecule, CD44, on
      ovarian tumour cells could be important in ovarian cancer metastasis. In order to
      study this further, adhesion of six ovarian tumour lines to HA coated on to a
      plastic surface was investigated. Four lines bound to the HA coat and two lines
      did not. The adhesive lines were those that expressed high amounts of CD44, but
      the degree of adhesion was not closely correlated with CD44 expression. The
      results suggested that different tumour lines had different affinities for HA.
      Treatment of the HA coat with hyaluronidase substantially reduced adhesion.
      Adhesion was also partially reduced if the tumour cells were preincubated with
      either soluble HA, or anti-CD44 antibodies directed against the HA binding
      region. An antibody against a non-HA binding region only slightly blocked
      adhesion at high antibody concentrations. Only the CD44H isoform was detected by
      immunoprecipitation on the tumour cells. These results suggest that ovarian
      tumour cells can attach to immobilised HA via CD44H on the cell membrane.

PMID- 8878407
TI  - Nitric oxide reduces tumor cell adhesion to isolated rat postcapillary venules.
AB  - Adhesion of circulating tumor cells to microvascular endothelium plays an
      important role in tumor metastasis to distant organs. The purpose of this study
      was to determine whether nitric oxide (NO) would attenuate tumor cell adhesion
      (TCA) to naive or lipopolysaccharide (LPS)-treated postcapillary venules. A
      melanoma cell line, RPMI 1846, was shown to be much more adhesive to
      postcapillary venules isolated from rat mesentery than to corresponding
      precapillary arterioles. Although venules exposed to LPS for 4 h demonstrated an
      increased adhesivity for the melanoma cells, TCA to LPS-treated arterioles was
      not altered. Isolated venules exposed to DETA/NO (1 mM), an NO donor, for 30 min
      prior to tumor cell perfusion prevented the increment in adhesion induced by LPS
      and attenuated TCA to naive postcapillary venules. While L-arginine (100 microM),
      an NO precursor, failed to decrease TCA to naive postcapillary venules, this
      treatment abolished LPS-stimulated TCA to postcapillary venules. The effect of L
      arginine was reversed by administration of N(omega)-nitro-L-arginine methyl ester
      (L-NAME, 100 microM), an NO synthase (NOS) inhibitor. These observations indicate
      that both exogenous and endogenous NO modulate TCA to postcapillary venules. To
      assess the role of NO-induced activation of cGMP in the reduction in TCA produced
      by DETA/NO, two additional series of experiments were conducted. In the first
      series, LY-83583 (10 microM), a guanylyl cyclase inhibitor, was shown to
      completely reverse the effect of DETA/NO on TCA to both naive and LPS-activated
      postcapillary venules. On the other hand, administration of 8-bromoguanosine
      3',5'-cyclic monophosphate (8-B-cGMP) (1 mM), a cell permeant cGMP analog,
      mimicked the effect of DETA/NO and reduced TCA to LPS-stimulated postcapillary
      venules. These data suggest that (a) tumor cells are more likely to adhere to
      postcapillary venules than to corresponding precapillary arterioles, (b) LPS
      enhances TCA to postcapillary venules, (c) both exogenously applied (DETA/NO) and
      endogenously generated (L-arginine) NO attenuate the enhanced adhesion induced by
      LPS, but only DETA/NO reduced TCA to naive postcapillary venules, and (d) the NO
      induced reduction in TCA to LPS-activated postcapillary venules occurs by a cGMP
      dependent mechanism.

PMID- 8878408
TI  - Expression of cysteine protease inhibitors in human gliomas and meningiomas.
AB  - Increased levels of human cysteine proteases have been implicated in the
      progression of tumors from the premalignant to the malignant state. The
      physiological activities of these proteases are regulated by their interactions
      with specific inhibitors. To our knowledge there have been no previous reports
      about the cysteine protease inhibitors (CPIs) in human brain tumors. In the study
      reported here, we determined CPI activity during glioma progression and compared
      that with normal human brain tissue. We also determined CPI activities in
      meningioma and glioblastoma cell lines in vitro. This activity was significantly
      higher in normal brain tissue and low-grade glioma than in anaplastic astrocytoma
      and glioblastoma. CPI activity was significantly higher in benign and atypical
      meningioma cell extracts in comparison with those from malignant meningiomas and
      with those from glioblastoma cell lines. After several passages, one benign
      meningioma cell line showed reduced levels of CPI and increased levels of
      cathepsin. Our results suggest that decreases in the activities of CPI may
      contribute to the malignant properties of brain tumors.

PMID- 8878409
TI  - Granulocyte-colony stimulating factor promotes invasion by human lung cancer cell
      lines in vitro.
AB  - The effects of exogenous and endogenous granulocyte colony-stimulating factor (G
      CSF) on invasion by cancer cells were studied, using lung cancer cell lines that
      produce G-CSF (NCI-H157) and lines that do not (PC-9 and NCI-H23). The invasive
      capacity of NCI-H157 cells was 26- to 27-fold higher than that of PC-9 and NCI
      H23 cells. The invasiveness of PC-9 cells was stimulated by exogenous G-CSF,
      while that of NCI-H157 cells was not. Antibodies against G-CSF blocked the
      stimulation of PC-9 cell invasiveness by exogenous G-CSF. Anti G-CSF antibodies
      also inhibited invasion by NCI-H157 cells in the absence of exogenous G-CSF.
      These results suggest that endogenous and exogenous G-CSF both stimulate invasion
      by lung cancer cells.

PMID- 8878410
TI  - Role of extracellular matrix proteins in regulation of human glioma cell invasion
      in vitro.
AB  - Primary brain tumors lack the metastatic behavior that is in part believed to be
      promoted by the extracellular matrix (ECM) components of the basement membrane.
      This study was intended to examine the influence of the ECM components present in
      the basement membrane that may act as natural barriers to tumor cell invasion. We
      examined the effect of type I and type IV collagens, fibronectin, laminin, and
      hyaluronic acid on the migration and invasion of four established glioblastoma
      cell lines, SNB19, U251, UWR1, and UWR2. Lower concentrations of all the ECM
      components induced the migration and invasion of all the cell lines. However, in
      the case of SNB19, laminin inhibited both migration and invasion in a
      concentration-dependent manner. We have also examined the influence of individual
      ECM components on the migration of cells from a spheroid to a monolayer on ECM
      component-coated coverslips. Consistent with the invasion studies using the
      modified Boyden chamber assays, lower concentrations of ECM components induced
      the migration of cells from spheroids to monolayer. Again, laminin inhibited the
      migration of cells from SNB19 spheroids. These results indicate that ECM
      components induce the invasion of glioma cells, apart from components like
      laminin, which may act as natural inhibitors.

PMID- 8878411
TI  - Kupffer cells and pit cells are not effective in the defense against
      experimentally induced colon carcinoma metastasis in rat liver.
AB  - The present study was performed to investigate processes involved in
      circumvention of the immune system by advanced stages of tumor growth in the
      liver. The efficacy of Kupffer cells and pit cells against cancer cells was
      tested in vivo in an experimental model of colon carcinoma metastasis in rat
      liver. Liver tumors were induced by administration of CC531 colon cancer cells
      into the vena portae. After 3 weeks, livers were obtained and partly fixed for
      electron microscopic procedures or frozen in liquid nitrogen for enzyme and
      immunohistochemistry at the light microscope level. The activation status of
      Kupffer cells was studied by expression of Ia-antigen (MHC class II) and by
      measurement of glucose-6-phosphate dehydrogenase (G6PDH) activity in the cells in
      situ as a measure of production of reactive oxygen species. Large numbers of
      Kupffer cells were found in liver parenchyma surrounding colon carcinomas when
      compared with levels in control livers, but these cells were not activated. Large
      numbers of activated monocytes and macrophages, cytotoxic T cells but only a few
      pit cells were found to be recruited to the boundary between liver parenchyma and
      tumors or their stroma. In those areas where cancer cells invaded liver
      parenchyma, only newly recruited macrophages and some Kupffer cells were present
      but few cytotoxic T cells or pit cells were found. The low activation status of
      Kupffer cells both in terms of production of reactive oxygen species and Ia
      antigen expression and the absence of significant numbers of pit cells at tumor
      sites suggest that Kupffer cells and pit cells do not play a significant role in
      advanced stages of tumor growth. High levels of prostaglandin E2 were detected in
      the parenchyma of livers containing tumors and transforming growth factor beta
      was detected in the stroma of the tumors, therefore suggest that cytotoxicity of
      newly recruited monocytes, macrophages and cytotoxic T cells may be limited in
      these stages because of local production of these immunosuppressive factors.

PMID- 8878412
TI  - Regulation of matrix metalloproteinase-1 and tissue inhibitor of
      metalloproteinase-1 in MCF-7 cells: comparison with regulatory mechanisms of pS2
      expression.
AB  - Regulation of two genes involved in tumor invasion, the matrix metalloproteinase
      (MMP)-1 and the tissue inhibitor of MMP (TIMP)-1, by activators of protein kinase
      C (PKC) or protein kinase A (PKA) was studied in MCF-7 mammary adenocarcinoma
      cells. The basal mRNA expression was undetectable for MMP-1 and low for TIMP-1.
      Treatment of MCF-7 cells with the phorbol ester 12-O-tetradecanoylphorbol-13
      acetate (TPA) (100 nM) was associated with a high expression of MMP-1 mRNA, as
      well as an induction of the level of TIMP-1 mRNA (5- to 10-fold). In the presence
      of actinomycin D (AMD, 4.0 microM), an inhibitor of transcription, these
      stimulatory effects of TPA were abolished. Similar responses were observed when
      protein synthesis was inhibited by cycloheximide (CHX, 50 microM). In the
      presence of the cyclic AMP (cAMP) analogue N6-benzoyl (N6-Bzl)-cAMP (500 microM),
      the MMP-1 mRNA was unaffected and still below the level of detection, whereas a
      non-significant increase (< 2-fold) in TIMP-1 mRNA was observed. The level of pS2
      mRNA, of which the induction by TPA in MCF-7 cells is a primary transcriptional
      event, was up-regulated (10- to 15-fold) by TPA (100 nM), whereas a much weaker
      increase (2- to 3-fold) was observed by treatment with N6-Bzl-cAMP (500 microM).
      Again, these stimulatory effects were counteracted by AMD (4.0 microM) and CHX
      (50 microM). These data suggest that activation of PKC but not of PKA may induce
      transcription of MMP-1 and TIMP-1, possibly by the synthesis of transcription
      factor(s), in transformed cells of epithelial origin.

PMID- 8878413
TI  - Genistein-stimulated adherence of prostate cancer cells is associated with the
      binding of focal adhesion kinase to beta-1-integrin.
AB  - The isoflavinoid genistein is a protein-tyrosine kinase inhibitor which has been
      identified as a putative cancer prevention agent. Its consumption is associated
      with a low incidence of clinical metastatic prostate cancer in the face of a
      sustained high incidence of organ-confined prostate cancer. We therefore
      undertook studies to examine genistein's effect upon cell adhesion as one
      possible mechanism by which it could be acting as an antimetastatic agent. A
      morphogenic analysis revealed that genistein caused cell flattening in a variety
      of cell lines: PC3-M, PC3, and DU-145 prostate carcinoma cells, as well as MCF-7
      breast carcinoma cells. Mechanistic studies focused on the highly metastatic PC3
      M cell line, and revealed that cell flattening was accompanied by an increase in
      cell adhesion. Further investigations demonstrated that focal adhesion kinase
      (FAK) accumulated in areas of focal cell attachment, and that this accumulation
      occurred only when cells were actively undergoing genistein-mediated morphologic
      change. Concurrent formation of a complex between the cell attachment molecule,
      beta-1-integrin, and FAK was shown to occur, and to correlate with transient
      activation of FAK activity. Genistein is presented as a novel investigative tool
      for use in the study of molecular events involved in the process of cell
      adhesion.

PMID- 8878414
TI  - Detection of the metastatic potential of blood-borne and immunomagnetically
      enriched epithelial cells by quantitative erbB-2 RT-PCR.
AB  - A quantitative competitive RT-PCR targeting the specific mRNA of c-erbB-2 is
      described. It is well known that in many cancers the c-erbB-2 gene dosage is
      elevated and/or the mRNA is overexpressed leading to a poor prognosis. The
      recently established method to enrich epithelial cells from peripheral blood made
      it reasonable and logical to develop a sophisticated competitive RT-PCR method to
      estimate the c-erbB-2 mRNA load of such cells. By this enrichment method it was
      discovered that cancer cells can be either isolated as single cells or clusters
      from patients' blood. The plausibility for their metastatic potential is derived
      from the measurement of the c-erbB-2 mRNA expression. A SKBR3 cell model
      suggested that the c-erbB-2 mRNA load is between 168 and 336 molecules per cell.
      Results of the quantitative competitive RT-PCR method can be used as a rational
      to determine the efficiency of anti-oncogenic therapies and as a criterion in
      adjuvant therapy decision.

PMID- 8878416
TI  - Psoriasis: further evidence of a key role for leukocytes.

PMID- 8878415
TI  - EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate
      carcinoma cells.
AB  - Carcinomas of the prostate and other lineages often present an autocrine
      stimulatory loop acting via the EGF receptor (EGFR). We have recently shown that
      EGFR-mediated signals enhance DU-145 prostate carcinoma cell transmigration of an
      extracellular matrix in vitro, and that this increased invasiveness was
      independent of proteolytic degradation of the matrix (Xie et al., 1995, Clin Exp
      Metastasis, 13, 407). To determine whether up-regulated EGFR signaling promotes
      tumor progression in vivo and to define the EGFR-induced cell property
      responsible, we inoculated athymic mice with genetically-engineered DU-145 cells.
      Parental DU-145 cells and those transduced to overexpress a full-length wild type
      (WT) EGFR formed tumors and metastasized to the lung when inoculated in the
      prostate and peritoneal cavity. The WT DU-145 tumors were more invasive. DU-145
      cells expressing a mitogenically-active, but motility-deficient (c'973) EGFR
      formed small, non-invasive tumors without evidence of metastasis. All three
      sublines demonstrated identical, EGFR-dependent rates of cell growth in vitro,
      suggesting that the differential invasiveness was not due to altered growth
      rates. To determine whether cell motility may be, in part, responsible for tumor
      invasiveness, we treated WT DU-145 intraperitoneal tumors with a pharmacologic
      agent (U73122) which blocks EGFR-mediated cell motility but not mitogenesis.
      Under this treatment regimen, the WT DU-145 cells formed tumors of similar
      numbers and size to those formed without treatment; however, these tumors were
      much less invasive. These data suggest that EGFR-mediated cell motility is an
      important mechanism involved in tumor progression, and that this cell property
      may represent a novel target to limit the spread of tumors.

PMID- 8878417
TI  - Mysterious cross talk between bone cells.

PMID- 8878418
TI  - Adhesion and signaling in vascular cell--cell interactions.

PMID- 8878419
TI  - Muscle wasting in insulinopenic rats results from activation of the ATP
      dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene
      transcription.
AB  - In normal subjects and diabetic patients, insulin suppresses whole body
      proteolysis suggesting that the loss of lean body mass and muscle wasting in
      insulinopenia is related to increased muscle protein degradation. To document how
      insulinopenia affects organ weights and to identify the pathway for accelerated
      proteolysis in muscle, streptozotocin-treated and vehicle-injected, pair-fed
      control rats were studied. The weights of liver, adipose tissue, and muscle were
      decreased while muscle protein degradation was increased 75% by insulinopenia.
      This proteolytic response was not eliminated by blocking lysosomal function and
      calcium-dependent proteases at 7 or 3 d after streptozotocin. When ATP synthesis
      in muscle was inhibited, the rates of proteolysis were reduced to the same level
      in insulinopenic and control rats suggesting that the ATP-dependent, ubiquitin
      proteasome pathway is activated. Additional evidence for activation of this
      pathway in muscle includes: (a) an inhibitor of proteasome activity eliminated
      the increased protein degradation; (b) mRNAs encoding ubiquitin and proteasome
      subunits were increased two- to threefold; and (c) there was increased
      transcription of the ubiquitin gene. We conclude that the mechanism for muscle
      protein wasting in insulinopenia includes activation of the ubiquitin-proteasome
      pathway with increased expression of the ubiquitin gene.

PMID- 8878420
TI  - Autoimmunity in Chagas' disease. Identification of cardiac myosin-B13 Trypanosoma
      cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas'
      cardiomyopathy patient.
AB  - Heart tissue destruction in chronic Chagas' disease cardiomyopathy (CCC) may be
      caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate
      decades after Trypanosoma cruzi infection. Indirect evidence suggests there is
      molecular mimicry between T. cruzi and heart tissue. In murine models of CCC,
      antibodies and CD4+ T cells recognize myosin, the major heart protein. We
      recently identified a heart-specific epitope of cardiac myosin heavy chain
      (residues 1442-1447, AAALDK) that is crossreactive with a homologous sequence
      (AAAGDK) of the immunodominant T. cruzi antigen B13. Furthermore, cardiac myosin
      B13 crossreactive antibodies are present in 100% CCC patients vs 14% asymptomatic
      T. cruzi-seropositive individuals (P = 2.3 x 10(-6)), suggesting a role for
      molecular mimicry between cardiac myosin and B13 in CCC pathogenesis. In this
      paper, we obtained heart-infiltrating T cell clones from CCC patients to assess
      whether molecular mimicry between cardiac myosin and B13 is directly involved in
      the genesis of heart lesions. We identified T cell clones derived from CCC heart
      lesions simultaneously responsive to cardiac myosin heavy chain (but not skeletal
      myosin heavy chain) and B13 T. cruzi protein, but could not find T cell clones
      primarily reactive to any T. cruzi antigen. Together with the association of
      myosin-B13 crossreactive antibodies with CCC, the present data strongly suggest
      the relevance of molecular mimicry between cardiac myosin and the T. cruzi
      protein B13 in the pathogenesis of heart lesions in chronic Chagas' disease
      cardiomyopathy.

PMID- 8878421
TI  - Acute lung injury fibroblast migration and invasion of a fibrin matrix is
      mediated by CD44.
AB  - Fibrosis results when myofibroblasts invade the wound fibrin provisional matrix.
      Extracellular matrix receptors on the cell surface mediate cell adhesion,
      migration, and invasion. Recent work with transformed cells indicates that these
      cells use the cell surface matrix receptor CD44 for migration and invasion. In
      this study, we examine whether lung fibroblasts, isolated from patients dying
      with acute alveolar fibrosis, use CD44 to invade a fibrin matrix. Consistent with
      a role for CD44 in mediating fibroblast invasion and subsequent tissue fibrosis,
      immunohistochemical analysis of lung tissue from patients who died from acute
      alveolar fibrosis after lung injury reveals CD44-expressing mesenchymal cells
      throughout newly formed fibrotic tissue. PCR, Western, and immunoprecipitation
      analysis demonstrate that the 85-kD CD44 isoform is expressed by acute lung
      injury fibroblasts. Consistent with a role in mediating matrix adhesion and
      migration ultrastructurally, CD44 was found uniformly over the cell surface and
      was found densely labeling filopodia and lamellipodia, highly motile structures
      involved in cell migration. To determine if lung injury fibroblasts use CD44 to
      invade fibrin, a fibrin gel model of fibrosis was used. By blocking the function
      of CD44 with monoclonal antibodies, fibroblast invasion into a fibrin matrix was
      inhibited. To examine the mechanism by which CD44 mediates fibroblast invasion,
      the role of CD44 in fibroblast migration and adhesion was evaluated. Anti-CD44
      antibody blocked fibroblast migration on the provisional matrix proteins
      fibronectin, fibrinogen, and hyaluronic acid. Additionally, fibroblast CD44
      mediated adhesion to the provisional matrix proteins fibronectin, fibrin, and
      hyaluronic acid, but not to laminin, a component of the basement membrane. These
      findings support the hypothesis that fibroblast CD44 functions as an adhesion
      receptor for provisional matrix proteins and is capable of mediating fibroblast
      migration and invasion of the wound provisional matrix resulting in the formation
      of fibrotic tissue.

PMID- 8878422
TI  - G-protein alpha subunit Gi(alpha)2 mediates erythropoietin signal transduction in
      human erythroid precursors.
AB  - Erythropoietin induces a dose-dependent increase in cytosolic calcium in human
      erythroblasts that is mediated by a voltage-independent Ca2+ channel. Inhibition
      of this response to erythropoietin by pertussis toxin suggests involvement of
      guanine nucleotide-binding regulatory proteins (G-proteins). The role of G
      proteins in regulation of the erythropoietin-modulated Ca2+ channel was
      delineated here by microinjection of G-protein modulators or subunits into human
      erythroid precursors. This is the first report on the use of microinjection to
      study erythropoietin signal transduction in normal precursor cells. Fura-2 loaded
      day-10 burst-forming units-erythroid-derived erythroblasts were used for
      microinjection and free intracellular calcium concentration ([Ca(i)]) was
      measured with digital video imaging. BCECF (1,2',7'-bis(2-carboxyethyl)-5-(and -6
      )-carboxyfluorescein) was included in microinjectate, and an increase in BCECF
      fluorescence was evidence of successful microinjection. Cells were microinjected
      with nonhydrolyzable analogues of GTP, GTPgammaS or GDPbetaS, which maintain the
      alpha subunit in an activated or inactivated state, respectively. [Ca(i)]
      increased significantly in a dose-dependent manner after microinjection of
      GTPgammaS. However, injection of GDPbetaS blocked the erythropoietin-induced
      calcium increase, providing direct evidence that activation of a G-protein is
      required. To delineate which G-protein subunits are involved, alpha or betagamma
      transducin subunits were purified and microinjected as a sink for betagamma or
      alpha subunits in the erythroblast, respectively. Transducin betagamma, but not
      alpha, subunits eliminated the calcium response to erythropoietin, demonstrating
      the primary role of the alpha subunit. Microinjected antibodies to Gi(alpha)2,
      but not Gi(alpha)1 or Gi(alpha)3, blocked the erythropoietin-stimulated [Ca(i)]
      rise, identifying Gi(alpha)2 as the subunit involved. This was confirmed by the
      ability of microinjected recombinant myristoylated Gi(alpha)2, but not Gi(alpha)1
      or Gi(alpha)3 subunits, to reconstitute the response of pertussis toxin-treated
      erythroblasts to erythropoietin. These data directly demonstrate a physiologic
      function of G-proteins in hematopoietic cells and show that Gi(alpha)2 is
      required in erythropoietin modulation of [Ca(i)] via influx through calcium
      channels.

PMID- 8878423
TI  - Triiodothyronine induces over-expression of alpha-smooth muscle actin, restricts
      myofibrillar expansion and is permissive for the action of basic fibroblast
      growth factor and insulin-like growth factor I in adult rat cardiomyocytes.
AB  - Effects of triiodothyronine (T3) on the expression of cytoskeletal and
      myofibrillar proteins in adult rat cardiomyocytes (ARC) were followed during two
      weeks of culture in the presence of 20% T3-depleted (stripped) FCS. Control
      cultures expressed mainly beta-myosin heavy chain (MHC) mRNA. T3 caused a switch
      to alpha-MHC expression and a dose-dependent increase of alpha-smooth muscle
      (alpha-sm) actin mRNA and protein. In parallel, the number of alpha-sm actin
      immunoreactive cells increased from 1% in controls to 29 and 62% in ARC treated
      with 5 and 100 nM T3. In the presence of T3, cells exhibited a higher beating
      rate than controls. The distribution of myofibrils in T3-treated cells was
      restricted to the perinuclear area with a sharp boundary. Only 5% of the control
      cells but 30 and 62% of the T3-treated (5 and 100 nM) ARC showed this restricted
      myofibrillar phenotype. Basic fibroblast growth factor (bFGF) which restricts
      myofibrillar growth and upregulates alpha-sm actin in ARC cultured with normal
      FCS had no effect on alpha-sm actin in ARC cultured in stripped FCS, but
      potentiated the effect of T3. In contrast, insulin-like growth factor I (IGF I),
      which suppresses alpha-sm actin and stimulates myofibrillogenesis in the presence
      of normal FCS suppressed T3-induced alpha-sm actin expression in stripped FCS.
      Thus, T3 appears to be permissive for the action of bFGF and IGF I on alpha-sm
      actin expression.

PMID- 8878424
TI  - Glanzmann thrombasthenia. Cooperation between sequence variants in cis during
      splice site selection.
AB  - Glanzmann thrombasthenia (GT), an autosomal recessive bleeding disorder, results
      from abnormalities in the platelet fibrinogen receptor, GP(IIb)-IIIa (integrin
      alpha(IIb)beta3). A patient with GT was identified as homozygous for a G-->A
      mutation 6 bp upstream of the GP(IIIa) exon 9 splice donor site. Patient platelet
      GP(IIIa) transcripts lacked exon 9 despite normal DNA sequence in all of the cis
      acting sequences known to regulate splice site selection. In vitro analysis of
      transcripts generated from mini-gene constructs demonstrated that exon skipping
      occurred only when the G-->A mutation was cis to a polymorphism 116 bp upstream,
      providing precedence that two sequence variations in the same exon which do not
      alter consensus splice sites and do not generate missense or nonsense mutations,
      can affect splice site selection. The mutant transcript resulted from utilization
      of a cryptic splice acceptor site and returned the open reading frame. These data
      support the hypothesis that pre-mRNA secondary structure and allelic sequence
      variants can influence splicing and provide new insight into the regulated
      control of RNA processing. In addition, haplotype analysis suggested that the
      patient has two identical copies of chromosome 17. Markers studied on three other
      chromosomes suggested this finding was not due to consanguinity. The restricted
      phenotype in this patient may provide information regarding the expression of
      potentially imprinted genes on chromosome 17.

PMID- 8878425
TI  - Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects.
AB  - All glucokinase gene mutations identified to date have been localized to exons
      that are common to the pancreatic and hepatic isoforms of the enzyme. While
      impaired insulin secretion has been observed in glucokinase-deficient subjects
      the consequences of this mutation on hepatic glucose metabolism remain unknown.
      To examine this question hepatic glycogen concentration was measured in seven
      glucokinase-deficient subjects with normal glycosylated hemoglobin and 12 control
      subjects using 13C nuclear magnetic spectroscopy during a day in which three
      isocaloric mixed meals were ingested. The relative fluxes of the direct and
      indirect pathways of hepatic glycogen synthesis were also assessed using [1
      13C]glucose in combination with acetaminophen to noninvasively sample the hepatic
      UDP-glucose pool. Average fasting hepatic glycogen content was similar in
      glucokinase-deficient and control subjects (279+/-20 vs 284+/-14 mM; mean+/-SEM),
      and increased in both groups after the meals with a continuous pattern throughout
      the day. However, the net increment in hepatic glycogen content after each meal
      was 30-60% lower in glucokinase-deficient than in the control subjects
      (breakfast, 46% lower, P < 0.02; lunch, 62% lower, P = 0.002; dinner; 30% lower,
      P = 0.04). The net increment over basal values 4 h after dinner was 105 +/-18 mM
      in glucokinase-deficient and 148+/-11 mM in control subjects (P = 0.04). In the 4
      h after breakfast, flux through the gluconeogenic pathway relative to the direct
      pathway of hepatic glycogen synthesis was higher in glucokinase-deficient than in
      control subjects (50+/-2% vs 34+/-5%; P = 0.038). In conclusion glucokinase
      deficient subjects have decreased net accumulation of hepatic glycogen and
      relatively augmented hepatic gluconeogenesis after meals. These results suggest
      that in addition to the altered beta cell function, abnormalities in liver
      glycogen metabolism play an important role in the pathogenesis of hyperglycemia
      in patients with glucokinase-deficient maturity onset diabetes of young.

PMID- 8878427
TI  - Direct preconditioning of cultured chick ventricular myocytes. Novel functions of
      cardiac adenosine A2a and A3 receptors.
AB  - Preconditioning with brief ischemia before a sustained period of ischemia reduces
      infarct size in the perfused heart. A cultured chick ventricular myocyte model
      was developed to investigate the role of adenosine receptor subtypes in cardiac
      preconditioning. Brief hypoxic exposure, termed preconditioning hypoxia, prior to
      prolonged hypoxia, protected myocytes against injury induced by the prolonged
      hypoxia. Activation of the adenosine A1 receptor with CCPA or the A3 receptor
      with C1-IB-MECA can replace preconditioning hypoxia and simulate preconditioning,
      with a maximal effect at 100 nM. While activation of the A2a receptor by 1 microM
      CGS21680 could not mimic preconditioning, its stimulation during preconditioning
      hypoxia, however, attenuated the protection against hypoxia-induced injury.
      Blockade of A2a receptors with the selective antagonist CSC (1 microM) during
      preconditioning hypoxia enhanced the protective effect of preconditioning.
      Nifedipine, which blocked the A2a receptor-mediated calcium entry, abolished the
      A2a agonist-induced attenuation of preconditioning. Isoproterenol, forskolin, and
      BayK 8644, which stimulated calcium entry, also attenuated preconditioning.
      Nifedipine blocked the increase in calcium uptake by these agents as well as
      their attenuating effect on preconditioning. The present study provides the first
      evidence that the adenosine A3 receptor is present on ventricular myocytes and
      can mediate simulation of preconditioning. The data demonstrate, for the first
      time, that activation of the A2a receptor antagonizes the preconditioning effect
      of adenosine, with increased calcium entry during the preconditioning stimuli as
      a novel mechanism.

PMID- 8878426
TI  - Genetic linkage of IgG autoantibody production in relation to lupus nephritis in
      New Zealand hybrid mice.
AB  - F1 hybrids of New Zealand black (NZB) and New Zealand white (NZW) mice are a
      model of human systemic lupus erythematosus. These mice develop a severe immune
      com-plex-mediated nephritis, in which antinuclear autoantibodies are believed to
      play the major role. We used a genetic analysis of (NZB x NZW)F1 x NZW backcross
      mice to provide insight into whether different autoantibodies are subject to
      separate genetic influences and to determine which autoantibodies are most
      important in the development of lupus-like nephritis. The results showed one set
      of loci that coordinately regulated serum levels of IgG antibodies to double
      stranded DNA, single-stranded DNA, total histones, and chromatin, which
      overlapped with loci that were linked to the production of autoantibodies to the
      viral glycoprotein, gp70. Loci linked with anti-gp70 compared with antinuclear
      antibodies demonstrated the strongest linkage with renal disease, suggesting that
      autoantibodies to gp70 are the major pathogenic antibodies in this model of lupus
      nephritis. Interestingly, a distal chromosome 4 locus, Nba1, was linked with
      nephritis but not with any of the autoantibodies measured, suggesting that it
      contributes to renal disease at a checkpoint distal to autoantibody production.

PMID- 8878428
TI  - Mechanisms of impaired beta-adrenoceptor-induced airway relaxation by interleukin
      1beta in vivo in the rat.
AB  - We studied the in vivo mechanism of beta-adrenergic receptor (beta-AR)
      hyporesponsiveness induced by intratracheal instillation of interleukin-1beta (IL
      1beta, 500 U) in Brown-Norway rats. Tracheal and bronchial smooth muscle
      responses were measured under isometric conditions ex vivo. Contractile responses
      to electrical field stimulation and to carbachol were not altered, but maximal
      relaxation induced by isoproterenol (10(-6)-10(-5) M) was significantly reduced
      24 h after IL-1beta treatment in tracheal tissues and to a lesser extent, in the
      main bronchi. Radioligand binding using [125I]iodocyanopindolol revealed a 32+/
      7% reduction in beta-ARs in lung tissues from IL-1beta-treated rats, without any
      significant changes in beta2-AR mRNA level measured by Northern blot analysis.
      Autoradiographic studies also showed significant reduction in beta2-AR in the
      airways. Isoproterenol-stimulated cyclic AMP accumulation was reduced by IL-1beta
      at 24 h in trachea and lung tissues. Pertussis toxin reversed this
      hyporesponsiveness to isoproterenol but not to forskolin in lung tissues. Western
      blot analysis revealed an IL-1beta-induced increase in Gi(alpha) protein
      expression. Thus, IL-1beta induces an attenuation of beta-AR-induced airway
      relaxation through mechanisms involving a reduction in beta-ARs, an increase in
      Gi(alpha) subunit, and a defect in adenylyl cyclase activity.

PMID- 8878429
TI  - Requirement for increased IL-10 in the development of B-1 lymphoproliferative
      disease in a murine model of CLL.
AB  - Malignant B-1 cells derived from NZB mice, a murine model of spontaneous
      autoimmunity and B cell lymphoproliferative disease, produce significantly higher
      levels of IL-10 mRNA than normal B-1 or B cells. IL-10 may act as an autocrine
      growth factor for the expansion of malignant B-1 cells. In order to determine if
      elevated endogenous production of IL-10 was a required element for the malignant
      transformation of B-1 cells in NZB mice, backcross animals were studied for the
      linkage between elevated IL-10 expression and the presence of lymphoid
      malignancy. The phenotypes of aged (NZB x DBA/2)F1 x NZB animals were determined
      and a strong correlation was found between the elevated levels of IL-10 mRNA and
      the development of B-1 malignant clones. In contrast, an increased level of IL-10
      message was not associated with elevated serum IgM or the presence of anemia or
      reticulocytosis which is mainly seen in response to autoantibody production.
      These results indicate that, at least in NZB, the autoimmunity and
      lymphoproliferation phenotypes are not linked genetically. IL-10 may enhance
      proliferation and the development of B-1 cell malignancy rather than antibody
      production by the B-1 cell subpopulation. Thus, IL-10 plays an important role in
      B-1 malignancies, and downregulation of IL-10 could be a likely site for
      intervention in B cell malignancies.

PMID- 8878430
TI  - Human immunodeficiency virus-1 (HIV-1) gp120 superantigen-binding serum
      antibodies. A host factor in homosexual HIV-1 transmission.
AB  - HIV-1 gp120 is an immunoglobulin superantigen which can bind to preimmune serum
      Ig. We hypothesize that levels of such preimmune antibodies vary in the
      population and might affect host resistance or susceptibility to viral
      transmission. This study tests two predictions: (a) levels of preimmune anti
      gpl20 Igs are a polymorphic trait; and, (b) these levels are correlated with
      resistance or susceptibility to HIV-1 transmission. The first prediction was
      confirmed in a longitudinal study of a low-risk seronegative population. In this
      group, levels of both endogenous anti-gpl20 IgM and IgG varied widely, but were
      characteristic and stable for each individual. The second prediction was
      addressed in a study of participants of the Multicenter AIDS Cohort Study, in
      which men "susceptible" and "resistant" to HIV infection were identified based on
      numbers of sexual partners and eventual seroconversion. Specimens consisted of
      archival sera obtained > 2 yr before seroconversion. Men in the susceptible
      population (low-risk seroconverters) were distinguished by low levels of anti
      gpl20 IgG. We conclude that the level of preimmune anti-gpl20 IgG is a
      polymorphic population trait, and low levels are a potentially specific and
      significant factor in homosexual transmission of HIV infection.

PMID- 8878431
TI  - Molecular identification of T cells that respond in a primary bulk culture to a
      peptide derived from a platelet glycoprotein implicated in neonatal alloimmune
      thrombocytopenia.
AB  - Neonatal alloimmune thrombocytopenia induced by the human platelet alloantigen 1a
      (HPA1a) is characterized by generation of alloantibodies by a mother who is
      homozygous for the HPA1b alloantigen and almost always HLA-DRB3*0101. The disease
      is viewed as B cell mediated but the linkage with HLA is indicative of a role for
      T cells. The HPA1a and HPA1b allotypes are defined, respectively, by Leu and Pro
      at amino acid 33 of the beta-chain of the platelet integrin GPIIbIIIa
      (alpha(IIb)beta3). Under the assumption that the same polymorphism may control
      both the B cell epitope and constitute the MHC-bound peptide, we restimulated
      PBMC from a woman with an affected child with a synthetic peptide from this
      polymorphic region. Molecular analysis of the responding T cell repertoire
      identified two T cells which predominated in cultures stimulated with the
      alloantigen peptide and which were absent in cultures with the autoantigen
      peptide. In spite of the use of different V families, sequence of the CDR3 region
      of the T cell receptor (TCR) beta-chain revealed the presence of a shared motif,
      L-P-S/T. Oligonucleotide probes specific for the CDR3 sequence indicated that
      these T cells were present in the PBMC at the highest levels immediately after
      delivery of the affected infant and their frequency dropped at later times.

PMID- 8878432
TI  - A carboxy-terminal truncation of human alpha-galactosidase A in a heterozygous
      female with Fabry disease and modification of the enzymatic activity by the
      carboxy-terminal domain. Increased, reduced, or absent enzyme activity depending
      on number of amino acid residues deleted.
AB  - Fabry disease is an X-linked disorder of glycosphingolipid metabolism caused by a
      deficiency of alpha-galactosidase A (alpha-Gal A). We identified a novel mutation
      of alpha-Gal A gene in a family with Fabry disease, which converted a tyrosine at
      codon 365 to a stop and resulted in a truncation of the carboxy (C) terminus by
      65 amino acid (AA) residues. In a heterozygote of this family, although the
      mutant and normal alleles were equally transcribed in cultured fibroblasts,
      lymphocyte alpha-Gal A activity was approximately 30% of the normal control and
      severe clinical symptoms were apparent. COS-1 cells transfected with this mutant
      cDNA showed a complete loss of its enzymatic activity. Furthermore, those
      cotransfected with mutant and wildtype cDNAs showed a lower alpha-Gal A activity
      than those with wild type alone (approximately 30% of wild type alone), which
      suggested the dominant negative effect of this mutation and implied the
      importance of the C terminus for its activity. Thus, we generated mutant cDNAs
      with various deletion of the C terminus, and analyzed. Unexpectedly, alpha-Gal A
      activity was enhanced by up to sixfold compared with wild-type when from 2 to 10
      AA residues were deleted. In contrast, deletion of 12 or more AA acid residues
      resulted in a complete loss of enzyme activity. Our data suggest that the C
      terminal region of alpha-Gal A plays an important role in the regulation of its
      enzyme activity.

PMID- 8878433
TI  - Impaired glucose homeostasis in insulin-like growth factor binding protein-1
      transgenic mice.
AB  - Transgenic mice that overexpressed IGFBP-1 are hyperinsulinemic in the first week
      of life and gradually develop fasting hyperglycemia. In adult transgenic mice,
      the hypoglycemic response to IGF-I but not insulin or des (1-3) IGF-I was
      attenuated (P < 0.05) compared with wild-type mice. Furthermore, in isolated
      adipocytes from transgenic mice, the stimulatory effect of IGF-I but not insulin
      on 2-deoxy-[3H]-glucose uptake was reduced (P < 0.02). In contrast, in isolated
      soleus muscle, the effects of both IGF-I and insulin on 2-deoxy-3H-glucose uptake
      and on [3H]-glucose incorporation into glycogen were significantly reduced
      compared to wild-type mice. The decline in specific activity of the 2-deoxy-3H
      glucose, a measure of glucose appearance in the circulation, was more marked in
      transgenic animals (P < 0.05). In addition, tissue uptake of glucose was
      significantly higher in diaphragm, heart, intestine, liver, soleus muscle, and
      adipose tissue from fasting transgenic mice. Plasma concentrations of alanine,
      lysine, and methionine were also elevated in transgenic mice. These data suggest
      that overexpression of IGFBP-1 attenuates the hypoglycemic effect of endogenous
      IGF-I, which is initially compensated for by enhanced pancreatic insulin
      production. However, in adult mice pancreatic insulin content is reduced, insulin
      resistance is demonstrable in skeletal muscle and fasting hyperglycemia develops.

PMID- 8878434
TI  - Insulin and insulin-like growth factor I differentially induce alpha1-adrenergic
      receptor subtype expression in rat vascular smooth muscle cells.
AB  - Hyperinsulinemia has been implicated as an important risk factor for the
      development of accelerated cardiovascular disease. We wondered if insulin or IGF
      I induced expression of alpha1 adrenergic receptors in vascular smooth muscle
      cells (VSMCs) which could enhance smooth muscle contraction and cell growth
      activated by catecholamines. Rat aortic VSMCs were incubated with insulin or IGF
      I for various times and expression of alpha1 receptors was detected using
      [3H]prazosin binding. Both insulin and IGF-I increased alpha1 receptor number;
      also, these peptides increased expression of the alpha1D receptor gene with no
      change in expression of the alpha1B receptor gene as detected by RNase protection
      assays. Using Western blotting, we found that these peptides increased expression
      of the alpha1D receptor subtype in these cells. Increased expression of the
      alpha1D receptor mRNA was inhibited by the receptor tyrosine kinase inhibitor
      genistein and the PI 3-kinase inhibitor wortmannin but was not inhibited by
      protein kinase C inhibitor H7 or the L-type calcium channel blocker nifedipine.
      Preincubation of cells with insulin or IGF-I enhanced subsequent norepinephrine
      stimulation of mitogen activated kinase activity. These results suggest that
      insulin/IGF-I regulate expression of alpha1 receptors in VSMCs and potentially
      enhance the effects of catecholamines in settings of hyperinsulinemia.

PMID- 8878435
TI  - Demonstration of an osteoblast defect in two cases of human malignant
      osteopetrosis. Correction of the phenotype after bone marrow transplant.
AB  - Osteopetrosis is an inherited disorder characterized by bone sclerosis due to
      reduced bone resorption. Here we report that human osteopetrotic osteoblast-like
      (Ob) cells express a defective phenotype in primary cultures in vitro, and that
      bone marrow transplant (BMT) corrects osteoblast function. DNA analysis at
      polymorphic short-tandem repeat loci from donor, recipient, and primary Ob-like
      cells pre-BMT and 2 yr post-BMT revealed that Ob were still of recipient origin
      post-BMT. Osteopetrotic Ob-like cells obtained pre-BMT showed normal and abnormal
      1,25(OH)2D3-induced alkaline phosphatase (ALPase) and osteocalcin production,
      respectively, and failed to produce macrophage colony-stimulating factor (M-CSF)
      in response to IL-1a and TNF-alpha. These parameters were all normalized in
      primary Ob-like cells prepared 2 yr post-BMT. X-linked clonality analysis at the
      human androgen receptor (HUMARA) locus revealed that osteoblasts showed a
      polyclonal and an oligoclonal derivation pre- and post-BMT respectively,
      indicating that a limited number of progenitor reconstituted this population.
      Because osteoblasts were still of recipient origin post-BMT, this suggests that
      functional osteoclasts, due to the replacement of hematopoeitic cells, provided a
      local microenvironment in vivo triggering the differentiation and/or recruitment
      of a limited number of functional osteoblasts.

PMID- 8878436
TI  - Characterization of a germline Vk gene encoding cationic anti-DNA antibody and
      role of receptor editing for development of the autoantibody in patients with
      systemic lupus erythematosus.
AB  - We found previously that cationic anti-DNA autoantibodies (autoAbs) have
      nephritogenic potential and usage of a specific germline Vk gene, A30, has major
      influences on cationic charge of the autoAb in human lupus nephritis. In the
      present study, we have characterized A30 germline Vk gene using cosmid cloning
      technique in patients with SLE. A30 gene locus locates in less than 250 kb from
      the Ck region, and the cationic anti-DNA mRNA used the upstream Jk2 gene,
      indicating that cationic anti-DNA mRNA is a product of primary gene
      rearrangement. By using PCR technique, we found that A30 gene locus in the genome
      was defective in eight out of nine SLE patients without nephritis. In contrast,
      all nine patients with lupus nephritis had intact A30 gene. The presence and
      absence of A30 gene was associated with the development of lupus nephritis or not
      (P < 0.01, by Fisher's exact test, two-sided). It was thus suggested that absence
      of functional A30 gene may rescue from developing lupus nephritis in the
      patients. A30 is reported to be a potentially functional but rarely expressed Vk
      gene in humans. It is possible that normal B cells edit primarily rearranged A30
      gene with autoreactive potentials by receptor editing mechanism for changing the
      affinity of the B cell Ag receptor to avoid self-reactivity, whereas SLE B cells
      may have a defect in this mechanism. Indeed, we found that normal B cells edit
      A30-Jk2 gene in their genome possibly by inversion mechanism, whereas SLE B cells
      contain rearranged A30-Jk2-Ck gene in the genome and express A30-associated mRNA,
      suggesting that receptor editing mechanism is also defective in patients with
      SLE. Our study suggests that polymorphism of Ig Vk locus, and failure of receptor
      editing may contribute to the development of pathogenic anti-DNA responses in
      humans.

PMID- 8878437
TI  - Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL
      10-transduced islet-specific Th1 lymphocytes. A gene therapy model for autoimmune
      diabetes.
AB  - Four pancreatic islet-specific CD4+ helper T (Th) 1 (Th1) clones and two Th1
      clones transduced with an SRalpha promoter-linked murine IL-10 (mIL-10) cDNA of
      2.0-6.0 x 10(6) cells were adoptively transferred to nonobese diabetic (NOD) mice
      at age 8 d. Cyclophosphamide (CY) was administered at age 37 d (plus CY), and the
      incidence of diabetes and the histological grade of insulitis were examined at
      age 47 d. After the adoptive transfer of IL-10-transduced Th1 cells, polymerase
      chain reaction (PCR) and reverse-transcription (RT)-PCR detected the neo gene and
      the retrovirus vector-mediated IL-10 mRNA in situ in recipient islets,
      respectively. RT-PCR detected the decrease of IFN-gamma mRNA relative to IL-10
      mRNA in IL-10-transduced Th1 clones in vitro and also in recipient islets. All
      four wild type Th1 clones plus CY induced the insulitis grade of 2.75 and
      diabetes in 66% of recipient NOD mice. IL-10-transduced two Th1 clones plus CY
      induced periinsulitis with the grade of 1.43 and diabetes in 8.0%. The 1:1
      mixture of wild type Th1 cells and IL-10-transduced Th1 cells plus CY induced
      periinsulitis with the grade of 1.85 and diabetes in 20%. The suppression of
      diabetes through decreasing IFN-gamma mRNA by the tissue-specific delivery of IL
      10 to pancreatic islets with IL-10-transduced Th1 cells affords us the starting
      basis to develop the gene therapy for autoimmune diabetes.

PMID- 8878438
TI  - Functional characterization of calcium-sensing receptor mutations expressed in
      human embryonic kidney cells.
AB  - The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that plays a
      key role in extracellular calcium ion homeostasis. We have engineered 11 CaR
      mutants that have been described in the disorders familial benign hypercalcemia
      (FBH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant
      hypocalcaemia (ADH), and studied their function by characterizing intracellular
      calcium [Ca2+]i transients in response to varying concentrations of extracellular
      calcium [Ca2+]o or gadolinium [Gd3+]o. The wild type receptor had an EC50 for
      calcium (EC50[Ca2+]o) (the value of [Ca2+]o producing half of the maximal
      increase in [Ca2+]i) of 4.0 mM (+/- 0.1 SEM). However, five missense mutations
      associated with FBH or NSHPT, (P55L, N178D, P221S, R227L, and V817I) had
      significantly higher EC50[Ca2+]os of between 5.5 and 9.3 mM (all P < 0.01).
      Another FBH mutation, Y218S, had an EC50[Ca2+]o of > 50 mM but had only a mildly
      attenuated response to gadolinium, while the FBH mutations, R680C and P747fs,
      were unresponsive to either calcium or gadolinium. In contrast, three mutations
      associated with ADH, (F128L, T151M, and E191K), showed significantly reduced
      EC50[Ca2+]os of between 2.2 and 2.8 mM (all P < 0.01). These findings provide
      insights into the functional domains of the CaR and demonstrate that mutations
      which enhance or reduce the responsiveness of the CaR to [Ca2+]o cause the
      disorders ADH, FBH, and NSHPT, respectively.

PMID- 8878439
TI  - Chimeric mice carrying 'regional' targeted deletion of the angiotensin type 1A
      receptor gene. Evidence against the role for local angiotensin in the in vivo
      feedback regulation of renin synthesis in juxtaglomerular cells.
AB  - We have developed chimeric mice carrying 'regional' null mutation of the
      angiotensin type 1A (AT1A) receptor, the AT1 receptor subtype exclusively present
      in mouse juxtaglomerular (JG) cells. The chimeric mouse (Agtr1a -/- <--> +/+) is
      made up of wild-type (Agtr1a +/+) cells or cells homozygous for Agtr1a deletion
      (Agtr1a -/-). In the latter, the AT1A coding exon was replaced with a reporter
      gene, lacZ. In Agtr1a -/- <--> +/+ mice, these two clones of cells are found to
      be clustered and display patchy distributions in the kidney and heart. Tracking
      of lacZ activities in hetero- (Agtr1a +/-) and homozygous (Agtr1a -/-) deletion
      mutant offspring from Agtr1a -/- <--> +/+ mice revealed that the promoter
      activity of Agtr1a is localized in JG cells, afferent arteriolar walls,
      glomerular mesangial region and endothelial cells, and apical and basolateral
      proximal tubule membranes. The JG apparatuses of Agtr1a -/- mice are markedly
      enlarged with intense expression of renin mRNA and protein. In Agtr1a -/- <-->
      +/+ mice, these changes were proportional to the degree of chimerism. Within a
      given Agtr1a -/- <--> +/+ mouse, however, the degree of JG
      hypertrophy/hyperplasia and the expression of renin mRNA and protein were
      identical between Agtr1a +/+ and Agtr1a -/- cells. Thus, in the in vivo condition
      tested, the local interaction between angiotensin and the AT1 receptor on the JG
      cells has little functional contribution to the feedback regulation of JG renin
      synthesis.

PMID- 8878440
TI  - Dermal injection of immunocytes induces psoriasis.
AB  - Establishing direct and causal relationships among the confederacy of activated
      cell types present in psoriasis has been hampered by lack of an animal model.
      Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating
      immunocytes, and activated endothelial cells. The purpose of this study was to
      determine if psoriasis is primarily a disorder of keratinocytes or the immune
      system. Using a newly developed experimental system in which full-thickness human
      skin is orthotopically transferred onto severe combined immunodeficient mice,
      autologous immunocytes were injected into dermis, and the resultant phenotype
      characterized by clinical, histologic, and immunophenotypic analyses. Engraftment
      of samples included both uninvolved/ symptomless (PN) skin removed from patients
      with psoriasis elsewhere, or from healthy individuals with no skin disease (NN
      skin). In 10 different experiments involving 6 different psoriasis patients,
      every PN skin was converted to a full-fledged psoriatic plaque skin by injection
      of autologous blood-derived immunocytes. In all but one psoriatic patient, the
      immunocytes required preactivation with IL-2 and superantigens to convert PN skin
      into psoriatic plaque skin. In every case, resultant plaques were characterized
      by visible presence of flaking and thickened skin, loss of the granular cell
      layer, prominent elongation of rete pegs with a dermal angiogenic tissue
      reaction, and infiltration within the epidermis by T cells. Lesional skin
      displayed 20 different antigenic determinants of the psoriatic phenotype. None of
      the four NN skin samples injected with autologous immunocytes converted to
      psoriatic plaques. We conclude that psoriasis is caused primarily by the ability
      of pathogenetic blood-derived immunocytes to induce secondary activation and
      disordered growth of endogenous cutaneous cells including keratinocytes and
      vascular endothelium.

PMID- 8878441
TI  - Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.
AB  - We have identified and partially characterized the autoantibodies in sera of 60
      patients with chronic fatigue syndrome. Approximately 52% of the sera were found
      to react with nuclear envelope antigens. The combination of nuclear rim staining
      observed in immunofluorescence microscopy and immunoblot analysis of highly
      purified nuclear envelope proteins provided initial characterization of these
      autoantibodies. Further characterization showed that some sera immunoprecipitated
      the in vitro transcription and translation product of a human cDNA clone encoding
      the nuclear envelope protein lamin B1. The autoantibodies were of the IgG
      isotype. The occurrence of autoantibodies to a conserved intracellular protein
      like lamin B1 provides new laboratory evidence for an autoimmune component in
      chronic fatigue syndrome.

PMID- 8878442
TI  - Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration are responses to
      arterial injury that are highly important to the processes of restenosis and
      atherosclerosis. In the arterial balloon injury model in the rat, platelet
      derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are
      induced in the vessel wall and regulate these VSMC activities. Novel insulin
      sensitizing agents, thiazolidinediones, have been demonstrated to inhibit insulin
      and epidermal growth factor-induced growth of VSMCs. We hypothesized that these
      agents might also inhibit the effect of PDGF and bFGF on cultured VSMCs and
      intimal hyperplasia in vivo. Troglitazone (1 microM), a member of the
      thiazolidinedione class, produced a near complete inhibition of both bFGF-induced
      DNA synthesis as measured by bromodeoxyuridine incorporation (6.5+/-3.9 vs.
      17.6+/-4.3% cells labeled, P < 0.05) and c-fos induction. This effect was
      associated with an inhibition (by 73+/-4%, P < 0.01) by troglitazone of the
      transactivation of the serum response element, which regulates c-fos expression.
      Inhibition of c-fos induction by troglitazone appeared to occur via a blockade of
      the MAP kinase pathway at a point downstream of MAP kinase activation by MAP
      kinase kinase. At this dose, troglitazone also inhibited PDGF-BB-directed
      migration of VSMC (by 70+/-6%, P < 0.01). These in vitro effects were operative
      in vivo. Quantitative image analysis revealed that troglitazone-treated rats had
      62% (P < 0.001) less neointima/media area ratio 14 d after balloon injury of the
      aorta compared with injured rats that received no troglitazone. These results
      suggest troglitazone is a potent inhibitor of VSMC proliferation and migration
      and, thus, may be a useful agent to prevent restenosis and possibly
      atherosclerosis.

PMID- 8878443
TI  - Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and
      functional deficits in the heart.
AB  - The alpha-myosin heavy chain (alpha-MyHC) is the major contractile protein
      expressed in the myocardium of adult mice. We have produced mice carrying a null
      mutation of alpha-MyHC by homologous recombination in murine ES cells. Homozygous
      null animals die between 11 and 12 d in utero of gross heart defects, while alpha
      MyHC+/- heterozygotes survive and appear externally normal. The presence of a
      single functional alpha-MyHC+ allele in heterozygous animals results in reduced
      levels of the transcript and protein as well as fibrosis and alterations in
      sarcomeric structure. Examination of heart function using a working heart
      preparation revealed severe impairment of both contractility and relaxation in a
      subset of the alpha-MyHC+/- animals. Thus, two alpha-MyHC+ alleles are necessary
      for normal cardiac development, and hemizygosity for the normal allele can result
      in altered cardiac function.

PMID- 8878444
TI  - Processing and proliferative effects of human progastrin in transgenic mice.
AB  - Incompletely processed gastrins have been postulated to play a role in growth of
      the gastrointestinal tract, but few studies have examined the effects of
      progastrin on mucosal proliferation in vivo. Human gastrin gene expression and
      progastrin processing were therefore studied in transgenic mice containing a
      human gastrin (hGAS) minigene, and compared to processing in mice bearing an
      insulin gastrin (INS-GAS) transgene that overexpresses amidated gastrin.
      Progastrin processing was studied using region-specific antisera and
      radioimmunoassays, biosynthetic labeling, immunoprecipitation, and HPLC.
      Proliferative effects due to overexpression of processed and unprocessed gastrin
      in INS-GAS and hGAS mice, respectively, were determined using routine histology
      and BrdU incorporation. The pancreatic islets of INS-GAS mice were able to
      produce carboxyamidated G-17, resulting in a twofold elevation of serum amidated
      gastrin, marked thickening of the oxyntic mucosa, and an increased BrdU labeling
      index (LI) of the gastric body. In contrast, livers of adult hGAS mice expressed
      abundant human gastrin mRNA and human progastrin but were unable to process this
      peptide to the mature amidated form, resulting in markedly elevated serum
      progastrin levels and normal amidated gastrin levels. Nevertheless, there was a
      marked increase in the BrdU labeling index of the colon in hGAS mice (LI 7.46+/
      1.90%), as well as in INS-GAS mice (LI 6.16+/-1.17%), compared to age-matched,
      wild type control mice (LI 4.01+/-0.98%, P < 0.05). These studies suggest that
      incompletely processed gastrin precursors may contribute to colonic mucosal
      proliferation in vivo.

PMID- 8878446
TI  - Somatic cell mutation as a radiation biodosimeter and predictor of cancer risk
      and aging.

PMID- 8878445
TI  - 150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and
      allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia
      and modified low density lipoprotein.
AB  - The 150-kD oxygen-regulated protein (ORP150) was initially characterized based on
      its selective expression in astrocytes subjected to oxygen deprivation (Kuwabara,
      K., M. Matsumoto, J. Ikeda, O. Hori, S. Ogawa, Y. Maeda, K. Kitagawa, N. Imuta,
      K. Kinoshita, D.M. Stern, et al. 1996. J. Biol. Chem. 279:5025-5032). We have
      found that exposure of cultured human aortic smooth muscle cells and mononuclear
      phagocytes (MPs) to hypoxia (pO2 approximately 12-14 torr) induces ORP150
      transcripts and production of the antigen, whereas incubation with either
      hydrogen peroxide, sodium arsenite, heat shock, or 2-deoxyglucose was without
      effect. Tissue extracts prepared from human atherosclerotic lesions demonstrated
      expression of ORP150 mRNA and antigen, vs lack of ORP150 in samples from
      nonatherosclerotic areas. In situ hybridization using ORP150 riboprobes showed
      the mRNA to be predominantly [correction of predominately] present in macrophages
      in in atherosclerotic plaques. Furthermore, autoantibody to ORP150 was
      demonstrated in the serum of patients with severe atherosclerosis, consistent
      with inducible in vivo expression of ORP150. Introduction of antisense
      oligonucleotide for ORP150 selectively diminished hypoxia-mediated induction of
      ORP150 antigen and reduced the viability of hypoxic MPs, especially in the
      presence of modified (oxidized/acetylated) LDL. In support of a role for ORP150
      in the MPs' response to the microenvironment of an atheroma, the presence of
      oxidized LDL enhanced by approximately 10-fold ORP150 expression in hypoxic
      cultures. These data indicate that cells of the atherosclerotic vessel wall
      express ORP150 as part of a protective mechanism, potentially triggered by local
      hypoxia/hypoxemia and augmented by modified lipoproteins. The presence of
      antibody to ORP150 in sera of patients with severe atherosclerosis emphasizes the
      possibility that ORP150 may be a marker of vascular pathology.

PMID- 8878447
TI  - Anti-tumor promoting activity of canventol and its synthetic analogs through
      inhibition of protein isoprenylation.
AB  - Canventol, a synthetic compound, is a new inhibitor of tumor promotion on mouse
      skin by okadaic acid. We previously reported that canventol acts by inhibiting
      both protein isoprenylation and tumor necrosis factor-alpha (TNF-alpha) release.
      In this study we examined the potencies of 10 newly synthesized canventol analogs
      through their effect on mevalonate metabolism, and then examined 3 representative
      analogs for inhibition of protein isoprenylation. Since canventol in vitro did
      not directly inhibit farnesyl protein transferase or geranylgeranyl protein
      transferase-I, the effects of canventol and its synthetic analogs on the fate of
      [3H]mevalonate in cells were studied. Canventol at 500 microM changed the ratio
      of newly synthesized sterols (cholesterol and lathosterol) to ubiquinones from
      0.7 to 8.2 in NIH/3T3 cells which had previously been labeled with
      [3H]mevalonate, suggesting that the altered pattern of mevalonate metabolism is
      associated with inhibition of protein isoprenylation in the cells. We named this
      ratio the inhibition of protein isoprenylation index (IPI index). The 10 analogs
      showed a wide range of IPI indices. Two analogs, S3 and S9 had effects similar
      to, or stronger than, canventol. Three analogs, C44, C46 and C47, with lower IPI
      indices, inhibited tumor promotion on mouse skin slightly less than canventol
      itself did. This study shows that inhibition of protein isoprenylation in the
      cells, indicated by an increase in the IPI index, is a new biomarker for
      estimating inhibition of tumor promotion.

PMID- 8878448
TI  - Prevention by 2-mercaptoethane sulfonate and N-acetylcysteine of renal oxidative
      damage in rats treated with ferric nitrilotriacetate.
AB  - Ferric nitrilotriacetate (Fe-NTA) is a renal toxicant and carcinogen in rats and
      mice. We found that its administration results in formation of 4-hydroxy-2
      nonenal (HNE) in the renal proximal tubule cells of rats, and 8
      hydroxydeoxyguanosine (8-OHdG) adducts in their DNA, suggesting a role for
      oxidative stress. Since 2-mercaptoethane sulfonate (MESNA) and N-acetylcysteine
      (NAC), administered orally, have been shown to increase the kidney levels of free
      thiol groups, their influence on the renal toxicity and carcinogenicity induced
      by Fe-NTA was examined in the present study. Male Wistar rats were
      intraperitoneally injected with Fe-NTA (12 mg Fe/kg), and MESNA (100 mg/kg) or
      NAC (200 mg/kg) was given orally 1 h before and 1 h after this treatment. The
      animals were killed for tissue analyses 3 h after the Fe-NTA exposure. In accord
      with our previous reports, HNE-modified protein was detected in the proximal
      tubules of Fe-NTA-treated rats by means of immunohistochemistry. Likewise, levels
      of 8-OHdG in the renal nuclear DNA, lipid peroxides as thiobarbituric acid
      reactive substances in the kidneys, and blood urea nitrogen and creatinine in the
      serum were significantly increased by the Fe-NTA treatment. All of these changes
      were completely inhibited by oral administration of MESNA or NAC. These results
      suggest that both of these compounds can prevent the oxidative stress induced by
      Fe-NTA.

PMID- 8878449
TI  - Serial transplantation of adult T cell leukemia cells into severe combined
      immunodeficient mice.
AB  - The precise mechanism of the neoplastic cell growth of adult T cell leukemia
      (ATL) still remains unclear. In the present study, we have succeeded in serial
      transplantation of ATL cells from a patient into severe combined immunodeficient
      (SCID) mice. In this model, we found that only a leukemic cell clone from an ATL
      patient could be successively transplanted into SCID mice, although it was
      difficult to maintain leukemic cell clones in vitro, suggesting that the
      microenvironment provided by SCID mice is suitable for leukemic cell growth. We
      could not detect human T cell leukemia virus type I (HTLV-I) mRNA or interleukin
      2 (IL-2) mRNA in either the tumor cells growing in mice or the original leukemic
      cells. Thus, it appears that neither HTLV-I viral expression nor the IL-2
      autocrine mechanism is directly involved in the neoplastic cell growth of fresh
      ATL cells as well as HTLV-I-infected cell lines, at least in SCID mice. In
      addition, we could passage frozen cells and obtain a large number of expanded
      leukemic cells in this model. Such a serial transplantation model, which can
      avoid the changes in the nature of leukemic cells that are frequently observed in
      in vitro culture, and which can propagate leukemic cell clones, would be very
      suitable not only to study the mechanism of neoplastic cell growth, but also to
      test potential therapeutic agents for ATL.

PMID- 8878450
TI  - Establishment and characterization of choroid plexus carcinoma cell lines:
      connection between choroid plexus and immune systems.
AB  - Murine choroid plexus cell lines were produced from choroid plexus carcinoma
      generated in transgenic mice harboring the viral oncogene simian virus 40 large
      tumor antigen under transcriptional control of an intronic enhancer region from
      the human immunoglobulin heavy chain (IgH) gene. Two morphologically distinct
      cell lines have been cloned. These established cell lines retained the
      characteristics of choroid plexus cells in that they expressed such choroid
      plexus cell marker or related proteins as transthyretin and alpha2-macroglobulin.
      They were tumorigenic in nude mice. In the cell lines, the muA and muB (HE2)
      motifs within the IgH intronic enhancer were active and we also demonstrated the
      existence of the proteins binding to these motifs, suggesting a potential link
      between the choroid plexus and immune systems. It is considered that these
      binding proteins act as trans-activators for the enhancer and may belong to the
      class of ETS-related proteins. These cell lines and xenografts should be useful
      materials for analyses of choroid plexus functions.

PMID- 8878452
TI  - Expression and roles of heat shock proteins in human breast cancer.
AB  - Heat shock proteins (hsps) are thought to play important roles in the cell cycle
      and various processes of carcinogenesis. Therefore, we evaluated the expression
      of hsps, mainly hsp90 and hsp70, in human breast cancer tissues. Hsp90alpha mRNA
      was expressed at much higher levels in the cancerous tissue than in the non
      cancerous tissue. In addition, a close correlation between hsp90alpha mRNA
      expression and the proliferating-cell-nuclear-antigen labeling index (PCNA LI)
      was observed for the cancerous tissue. These findings suggest that increased
      expression of the hsp90alpha isoform may play a role in cell proliferation. On
      the other hand, hsp90beta mRNA expression was significantly higher in poorly
      differentiated carcinomas than in well differentiated carcinomas of the breast.
      The intracellular localization of hsp70 was consistent with that of ubiquitin. In
      specimens showing hsp70 in the nucleus, the PCNA LI was significantly high. Hsc73
      mRNA, a member of the hsp70 family, was also expressed at higher levels in
      cancerous tissues associated with a high PCNA LI than in non-cancerous tissues.
      These results suggest that hsp90alpha may play a role in cancer cell
      proliferation and that hsp90beta may contribute to cell differentiation and
      structural constitution. In addition, hsp70, especially hsc73, is related to
      ubiquitin and seems to be a marker for cancer proliferation.

PMID- 8878451
TI  - A comparative study of glioma cell lines for p16, p15, p53 and p21 gene
      alterations.
AB  - A total of 10 glioma cell lines were examined for alterations of the p16, p15,
      p53 and p21 genes, which are tumor suppressor genes or candidates with direct or
      indirect CDK-inhibitory functions. Genetic alterations (deletions or mutations)
      were frequently seen in the p16, p15 and p53 genes in these cell lines, but not
      in the p21 gene. When the states of the p16, p15 and p53 genes were compared
      among cell lines, all the cell lines showed abnormalities in at least 1 gene,
      often in 2 or 3 genes coincidentally, suggesting that dysfunction of these genes
      is closely related to glioma cell growth. Although alteration of all 3 genes was
      most frequent, there were cell lines having either p16/p15 or p53 or pl6 and p53
      gene alterations, suggesting that the time order of these genetic alterations was
      variable depending on the cell line. Among cell lines examined, one with
      homozygous p53 gene deletion seemed of particular practical value, since such a
      cell line might be useful in various studies, including investigation of the
      functions of various mutant p53 genes in the absence of heteromeric protein
      formation. On examination of the primary tumor tissues, the same alterations of
      the p16/p15 and p53 genes as detected in the cell lines were demonstrated in all
      6 cases examined: p16/p15 gene deletion in 1, p16 gene mutation in 1 and p53 gene
      mutations in 5 cases. This suggested that the p16/p15 and the p53 gene
      alterations and their combinations in at least some glioma cell lines reflected
      those in the primary glioma tissues.

PMID- 8878453
TI  - Glucocorticoid and estrogen receptors have elevated activity in human endometrial
      and ovarian tumors as compared to the adjacent normal tissues and recognize
      sequence elements of the H-ras proto-oncogene.
AB  - We examined the level of receptor binding in H-ras elements, using nuclear
      extracts derived from human endometrial and ovarian lesions and from adjacent
      normal tissue in gel retardation assays. We found increased binding of the
      glucocorticoid receptor (GR) to the H-ras GR element in more than 90% of
      endometrial tumors and in all ovarian tumors tested, as compared to the
      corresponding adjacent normal tissue. Additionally, we found elevated binding of
      the estrogen receptor (ER) in H-ras ER element in all pairs of ovarian
      tumor/normal tissue tested, whereas in ER-negative control breast tumor/normal
      tissue pairs, no differences in ER DNA-binding levels were observed. These
      results suggest that steroid hormone receptor binding could directly activate the
      H-ras oncogenic potency in human endometrial and ovarian lesions, providing
      additional evidence for the role of H-ras expression in hormonally responsive
      human cancers.

PMID- 8878454
TI  - Clonal heterogeneity in human esophageal squamous cell carcinomas on DNA
      analysis.
AB  - Cancers are thought to arise through multistep accumulation of somatic mutations
      in the progeny of a single cell. Multiple mutations may induce molecular
      intratumor heterogeneity. Therefore, we examined molecular clonal heterogeneity
      in esophageal squamous cell carcinomas. Twenty-four esophageal squamous cell
      carcinomas and associated lymph node metastases were examined for microsatellite
      alterations, and abnormalities of the p53 and transforming growth factor-beta
      type II receptor (TGF-beta RII) genes. There were eight cases (33%) showing
      different patterns of loss of heterozygosity in primary tumors and metastatic
      lymph nodes with microsatellite markers. On the other hand, the abnormalities of
      p53 were identical in all these cases. No mutation was detected in the simple
      repeated sequences of the TGF-beta RII gene. These results indicate that
      molecular clonal heterogeneity exists in esophageal squamous cell carcinomas.
      Therefore, care is necessary in preoperative genetic diagnosis using biopsy
      samples.

PMID- 8878455
TI  - p53 mutation in B-cell lymphoid neoplasms with reference to oncogene
      rearrangements associated with chromosomal translocations.
AB  - We investigated mutations of the p53 tumor suppressor gene in B-cell lymphoid
      neoplasms with reference to oncogene rearrangements associated with specific
      chromosomal translocations. These included 15 patients with a BCL1/PRAD1 gene
      rearrangement and/or PRAD1 overexpression, 45 with a BCL2 rearrangement, 2 with a
      BCL3 rearrangement, 24 with a BCL6 rearrangement, and 6 with both BCL2 and BCL6
      rearrangements. Thirty-six patients lacked detectable oncogene rearrangements.
      Genomic DNA was isolated from involved tissues or leukemic cells obtained at
      diagnosis and/or at relapse, and established cell lines. Polymerase chain
      reaction-mediated single-strand conformation polymorphism analysis and direct
      sequencing were performed to analyze abnormalities of the p53 gene. We detected
      p53 gene alterations in 18 of 128 patients, representing 21 of the total 151
      materials analyzed. In the total of 66 patients with an oncogene rearrangement
      studied at diagnosis, only one had a mutation; however, 6 of 37 patients studied
      at relapse showed p53 mutations. Sequential analysis revealed that the p53
      mutation was closely associated with transformation from follicular lymphoma to
      large cell lymphoma, exclusively in BCL2-positive lymphoma cases. Two of 13
      mutations observed in oncogene rearrangement-positive cases and cell lines were
      transitions at CpG dinucleotides. In contrast, the relationship between p53
      mutations and clinical behavior in oncogene rearrangement-negative cases was
      variable; 5 patients including one with indolent follicular lymphoma were
      positive for p53 mutation at initial presentation, and 2 of the 5 showed
      prolonged disease-free survival. Our findings suggest that p53 alteration
      exhibits diverse functions in the development and progression of B-cell tumors
      related to the presence or absence of oncogene rearrangement, and that
      chemotherapy-related influences may be involved in the occurrence of progression
      associated p53 mutations.

PMID- 8878456
TI  - Interleukin-6 and granulocyte colony-stimulating factor synergistically increase
      peripheral blood progenitor cells in myelosuppressive mice.
AB  - We previously reported a successful peripheral blood stem cell harvest by co
      administration of recombinant human (rh) interleukin-6 (IL-6) and rh granulocyte
      colony-stimulating factor (G-CSF) in normal mice. In the present study, to
      evaluate further the utility of this observation for autologous peripheral blood
      stem cell transplantation, we examined the effects of rhIL-6 and rhG-CSF on
      peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) in
      carboplatin (CBDCA)-induced and irradiation-induced myelosuppressive mouse
      models. After CBDCA administration, blood cell counts decreased to the nadir, and
      then recovered to a normal level. In this recovery phase, the peripheral CFU-GM
      level increased to 3.8-fold higher than the pretreatment level. Administration of
      rhIL-6 (10 microgram/day) alone induced a 40-fold increase in peripheral CFU-GM
      from the normal level at day 14. In combination with rhG-CSF (0.35
      microgram/day), which alone induced a 74-fold increase, rhIL-6 synergistically
      increased the CFU-GM level by 1200-fold. In irradiated mice, similar results were
      observed. Administration of rhIL-6 at 3 and 10 microgram/day significantly
      increased CFU-GM. Interestingly, in combination with rhG-CSF, a lower dose of
      rhIL-6 (1 microg/day) could induce CFU-GM increase. We also examined CFU-GM
      distribution in bone marrow, spleen and peripheral blood. Cytokine administration
      induced not only a change of CFU-GM distribution, but also an increase in total
      CFU-GM counts per mouse. These results suggest that co-administration of rhIL-6
      and rhG-CSF may be useful for autologous peripheral blood stem cell
      transplantation.

PMID- 8878457
TI  - Inhibition of nucleolar function and morphological change by adriamycin
      associated with heat shock protein 70 accumulation.
AB  - Adriamycin (ADR) has been considered to target mainly DNA metabolism in the
      nucleus. Recently, we observed the nuclear translocation of heat shock protein 70
      (HSP70) after ADR treatment. We examined which intranuclear changes might be
      related to this alteration of HSP70 localization. We found considerable
      alternations in the nucleolar morphology and function in ADR-treated tumor cells,
      i.e., a ring-shaped segregation of granular components of almost all nucleoli and
      a dramatic reduction of nucleolar 45S ribosomal precursor RNA biosynthesis in
      HeLa cells exposed to 100 microM ADR for 2 h. Concomitantly with these changes,
      HSP70 was concentrated into the nucleoli, as in the case of heat shock treatment.
      These results indicate a novel anticancer effect of ADR via the suppression of
      cellular protein biosynthesis, in addition to its effect on DNA.

PMID- 8878458
TI  - Evaluation of angiogenic inhibitors with an in vivo quantitative angiogenesis
      method using agarose microencapsulation and mouse hemoglobin enzyme-linked
      immunosorbent assay.
AB  - In the present work, using a previously reported in vivo quantitative tumor
      angiogenesis model, we attempted to ascertain whether this animal model is
      suitable for practical use in monitoring inhibitors of tumor angiogenesis. Mouse
      sarcoma-180 cells, human A431 cells or rat C6 cells microencapsulated in agarose
      beads were implanted s.c. into C57BL/6 mice. The level of blood vessel induction
      at the agarose pellet site was evaluated using mouse hemoglobin enzyme-linked
      immunosorbent assay on day 10 after implantation. Hydrocortisone, tetrahydro-S,
      medroxyprogesterone acetate, pentosan polysulfate and suramin inhibited blood
      vessel growth in our in vivo tumor-angiogenesis assay system, and heparin
      enhanced the antiangiogenic effects of hydrocortisone and tetrahydro-S. These
      results are almost entirely consistent with those observed in common assay
      systems, and suggest that this method may be useful for the identification and
      quantitative evaluation of inhibitors of tumor angiogenesis.

PMID- 8878459
TI  - Inhibition of liver metastasis of human gastric carcinoma by angiogenesis
      inhibitor TNP-470.
AB  - The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor,
      and mitomycin C (MMC), a representative anti-neoplastic agent, were investigated
      using our established liver-metastasizing gastric carcinoma line, AZ-H5c. AZ-H5c
      was injected into the spleen of nude mice which had been randomly divided into 4
      groups; a control group given saline solution, a group receiving 15 mg/kg TNP
      470, a group receiving 30 mg/kg TNP-470 and a group receiving 2 mg/kg MMC. TNP
      470 was given s.c. on alternate days for 5 weeks from day 10 after intrasplenic
      injection, and MMC was administered intraperitoneally (i.p.) once a week from day
      10 after intrasplenic injection. In the control group, liver metastasis developed
      in 13 of 16 mice (81%). Liver metastasis developed in 6 of 11 mice (55%)
      receiving MMC. In contrast, liver metastasis developed in 4 of 8 mice (50%)
      receiving 15 mg/kg TNP-470, and in 0 of 14 mice (0%) receiving 30 mg/kg TNP-470.
      However, TNP-470 had no effect on the tumor growth. These results indicate that
      the angiogenesis inhibitor TNP-470 has a strong inhibitory activity against in
      vivo liver metastasis of human gastric carcinoma.

PMID- 8878460
TI  - Inhibition of growth and metastasis of ovarian carcinoma by administering a drug
      capable of interfering with vascular endothelial growth factor activity.
AB  - The present study investigates the relationship between in vivo growth/metastasis
      of tumor cells and their capacity to produce the vascular endothelial growth
      factor (VEGF), as well as the regulation of tumor growth/metastasis using an
      angiogenesis-inhibitory drug. Two cloned tumor cell lines designated OV-LM and OV
      HM were isolated from a murine ovarian carcinoma OV2944. OV-LM and OV-HM cells
      grew in cultures at comparable rates. However, when transplanted s.c. into
      syngeneic mice, OV-HM exhibited a faster growth rate and a much higher incidence
      of metastasis to lymph nodes and lung. Histologically, intense neovascularization
      was detected in sections of OV-HM but not of OV-LM tumor. OV-HM and OV-LM tumor
      cells obtained from in vitro cultures expressed high and low levels of VEGF mRNA,
      respectively. A difference in VEGF mRNA expression was much more clearly observed
      between RNAs prepared from fresh OV-HM and OV-LM tumor masses: RNA from OV-HM
      contained larger amounts of VEGF mRNA, whereas RNA from OV-LM exhibited only
      marginal levels of VEGF mRNA. An angiogenesis-inhibitory drug, FR118487 inhibited
      the VEGF-mediated in vitro growth of endothelial cells but did not affect the
      expression in vitro of VEGF mRNA by OV-HM tumor cells. Intraperitoneal injections
      of FR118487 into mice bearing OV-HM tumors resulted in: (i) a subsequent growth
      inhibition of primary tumors; (ii) a marked decrease in neovascularization inside
      tumor masses expressing comparable levels of VEGF mRNA to those detected in
      control OV-HM masses; and (iii) almost complete inhibition of metastasis to lymph
      nodes and lung. These results indicate that growth/metastasis of tumor cells
      correlates with their VEGF-producing capacity and that an angiogenesis inhibitor,
      FR118487, inhibits tumor growth and metastasis through mechanism(s) including the
      suppression of VEGF function in vivo.

PMID- 8878461
TI  - The cytocidal activity of OK-432-activated mononuclear cells against human glioma
      cells is partly mediated through the Fas ligand/Fas system.
AB  - We have been applying an adoptive immunotherapy protocol to patients with
      malignant brain tumors using OK-432-activated peripheral blood mononuclear cells
      (OK-MCs). In order to elucidate the mechanism of OK-MCs' cytotoxicity, we
      examined the expression of Fas ligand mRNA in OK-MCs and the cytocidal activity
      of these cells against a human glioma cell line, T98G which expresses a high
      level of Fas. The expression of Fas ligand mRNA was low in non-treated peripheral
      blood mononuclear cells and was elevated by treatment with OK-432, irrespective
      of the dose employed. Apoptosis of T98G cells induced by OK-MCs was unequivocally
      inhibited by the pretreatment of T98 G cells with ZB4 monoclonal antibody, which
      binds to Fas and blocks the binding of Fas ligand to Fas. These data indicate
      that the cytotoxic activity of OK-MCs via apoptosis seems to be at least partly
      mediated by the Fas ligand/Fas system. Adoptive immunotherapy using the Fas
      ligand/Fas system could be a new treatment modality for human malignant brain
      tumors.

PMID- 8878463
TI  - Genetic screening in hereditary multiple endocrine neoplasia type 1: absence of a
      founder effect among Japanese families.
AB  - Ten Japanese families with hereditary multiple endocrine neoplasia type 1 (MEN1)
      were examined. Five DNA polymorphic markers on the long arm of chromosome 11 were
      analyzed for genetic screening of MEN1 in members of affected families, and
      disease carriers were identified before clinical manifestations. Unlike MEN1
      families in Newfoundland or in Tasmania, no consistent haplotypes were segregated
      with the disease in the Japanese families when defined by 5 nearby markers. The
      identification of asymptomatic disease carriers is of substantial clinical
      importance for early management, genetic counseling and to avoid unnecessary
      screening for non-disease carriers. However, genetic screening of family members
      by polymorphic markers could be useful only to each family, and no generally
      applicable markers were found for Japanese subjects with MEN1.

PMID- 8878462
TI  - Radioimmunotherapy for pancreatic carcinoma using (131)I-labeled monoclonal
      antibody Nd2 in xenografted nude mice.
AB  - We investigated the biodistribution, radiolocalization, and
      radioimmunotherapeutic potential of (131)I-labeled Nd2 in athymic nude mice
      bearing human pancreatic carcinoma xenografts. (131)I-Nd2 was accumulated at high
      levels in the tumor, in contrast to blood, liver, spleen, and other normal
      organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors
      of mice injected with 7.4 MBq of (131)I-Nd2 were 80% less than those of tumors
      before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen
      in histological sections of tumors of 7-week-treated mice. The growth of tumors
      in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then
      injected twice with 3.7 MBq of (131)I-Nd2 was suppressed over 7 weeks. Neither
      leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled
      Nd2. Thus (131)I-labeled Nd2 may have clinical application in the
      radioimmunotherapy of pancreatic cancer.

PMID- 8878464
TI  - Localization of small-cell lung cancer xenografts with iodine-125-, indium-111-,
      and rhenium-188-somatostatin analogs.
AB  - We examined the potential of radiolabeled somatostatin analogs, 125I-Tyr-3
      octreotide (125I-octreotide), (111)In-DTPA(diethylenetriaminepentaacetatic acid)
      D-Phe-1-octreotide (111In-octreotide), and 188Re-octreotide for targeting small
      cell lung cancer (SCLC) in a mouse model. Tyr-3-octreotide was labeled with 125I
      by the chloramine T method, and (111)In-octreotide was obtained as a kit, while
      188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled
      with 188Re by reducing disulfide bonds. The 125I-, 111In-, and 188Re-octreotides
      were injected i.v. into athymic mice bearing NCI-H69 tumors, and the
      biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes
      were 0.5+/-0.2, 0.3+/-0.1, 0.3+/-0.1 %ID/g, and tumor-to-blood ratios were 1.8,
      11.9, 1.2 at 8 h for 125I-, 111In-, and 188Re-octreotides, respectively.
      Accumulations of 111In-octreotide in normal tissues were lower than those of 125I
      and 188Re-octreotides. 188Re-octreotide can be used to localize SCLC lesions as
      efficiently as radioiodinated octreotide. However, 111In-octreotide was the most
      suitable agent to obtain high tumor-to-normal tissue contrast for localizing
      SCLC.

PMID- 8878466
TI  - Researchers resist copyright laws that could endanger data access.

PMID- 8878465
TI  - Subsite (cervix/endometrium)-specific risk and protective factors in uterus
      cancer.
AB  - In Japan the incidence of cervical cancer has been high, but has recently been
      decreasing gradually, while the incidence of endometrial cancer is running at
      lower levels but is gradually increasing. To clarify the common and/or specific
      risk and/or protective factors of cervical cancer(CC) in contrast with
      endometrial cancer (EC), a comparative case-control study was conducted at the
      Aichi Cancer Center Hospital, Japan. In total, 556 CC cases and 145 EC cases were
      included and 26,751 women, confirmed as free of cancer, were chosen as the common
      control group. Odds ratio and its 95% confidence interval (95%CI) for each
      exposure variable were estimated by using an unconditional logistic regression
      model adjusted for age and first-visit year. Habitual smoking and experience of
      pregnancy increased the risk of CC, while decreasing the risk of EC. Greater body
      mass index (>20), daily intake of fruit and more frequent intake of boiled or
      broiled fish (>1-2 times/week) decreased the risk of CC, whereas they increased
      the risk of EC. Daily intake of milk decreased the risk of CC. The results
      obtained from this study suggest that several EC-increasing risk factors are in
      fact CC-decreasing determinants. The observed risk reduction in both CC and EC by
      physical exercise and dietary control for health is noteworthy from the public
      health standpoint and warrants further investigation.

PMID- 8878467
TI  - Dengue fever in Delhi.

PMID- 8878468
TI  - California drops plan to destroy records.

PMID- 8878469
TI  - CJD variant stirs debate on release of data.

PMID- 8878470
TI  - Spongiform encephalopathies: a suspicious signature.

PMID- 8878471
TI  - Neurobiology: memories of nicotine.

PMID- 8878472
TI  - Human Genetics. Notch, stroke and dementia.

PMID- 8878473
TI  - Ribosomal RNA. Click here for methylation.

PMID- 8878474
TI  - Suntanning in hammerhead sharks.

PMID- 8878475
TI  - Human homologues of yeast helicase.

PMID- 8878476
TI  - Molecular analysis of prion strain variation and the aetiology of 'new variant'
      CJD.
AB  - Strains of transmissible spongiform encephalopathies are distinguished by
      differing physicochemical properties of PrPSc, the disease-related isoform of
      prion protein, which can be maintained on transmission to transgenic mice. 'New
      variant' Creutzfeldt-Jakob disease (CJD) has strain characteristics distinct from
      other types of CJD and which resemble those of BSE transmitted to mice, domestic
      cat and macaque, consistent with BSE being the source of this new disease. Strain
      characteristics revealed here suggest that the prion protein may itself encode
      disease phenotype.

PMID- 8878477
TI  - A transcriptional partner for MAD proteins in TGF-beta signalling.
AB  - The transforming-growth-factor-beta (TGF-beta) superfamily is critical for
      establishing mesoderm during early embryogenesis in Xenopus. The transcriptional
      activation of Mix.2, an immediate-early response gene specific to activin-like
      members of the TGF-beta superfamily, is associated with the rapid appearance of a
      site-specific DNA-binding activity that recognizes a fifty-base-pair regulatory
      element known as ARE in the Mix.2 promoter. Cloning of the site-specific DNA
      binding component of this activity revealed it to be a new winged-helix
      transcription factor and a direct target for signalling by the TGF-beta
      superfamily. XMAD2, a recently identified TGF-beta signal transducer, forms a
      complex with the transcription factor in an activin-dependent fashion to generate
      an activated ARE-binding complex. A model is proposed to explain how TGF-beta
      superfamily signals might regulate the expression of specific genes in the early
      embryo.

PMID- 8878478
TI  - Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke
      and dementia.
AB  - Stroke is the third leading cause of death, and vascular dementia the second
      cause of dementia after Alzheimer's disease. CADASIL (for cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy) causes a
      type of stroke and dementia whose key features include recurrent subcortical
      ischaemic events and vascular dementia and which is associated with diffuse white
      matter abnormalities on neuroimaging. Pathological examination reveals multiple
      small, deep cerebral infarcts, a leukoencephalopathy, and a non-atherosclerotic,
      non-amyloid angiopathy involving mainly the small cerebral arteries. Severe
      alterations of vascular smooth-muscle cells are evident on ultrastructural
      analysis. We have previously mapped the mutant gene to chromosome 19. Here we
      report the characterization of the human Notch3 gene which we mapped to the
      CADASIL critical region. We have identified mutations in CADASIL patients that
      cause serious disruption of this gene, indicating that Notch3 could be the
      defective protein in CADASIL patients.

PMID- 8878479
TI  - Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1.
AB  - Mutations in the genes encoding amyloid-beta precursor protein (APP), presenilin
      1 (PS1) and presenilin 2 (PS2) are known to cause early-onset, autosomal dominant
      Alzheimer's disease. Studies of plasma and fibroblasts from subjects with these
      mutations have established that they all alter amyloid beta-protein (beta APP)
      processing, which normally leads to the secretion of amyloid-beta protein
      (relative molecular mass 4,000; M(r) 4K; approximately 90% A beta1-40,
      approximately 10% A beta1-42(43)), so that the extracellular concentration of A
      beta42(43) is increased. This increase in A beta42(43) is believed to be the
      critical change that initiates Alzheimer's disease pathogenesis because A
      beta42(43) is deposited early and selectively in the senile plaques that are
      observed in the brains of patients with all forms of the disease. To establish
      that the presenilin mutations increase the amount of A beta42(43) in the brain
      and to test whether presenilin mutations act as true (gain of function)
      dominants, we have now constructed mice expressing wild-type and mutant
      presenilin genes. Analysis of these mice showed that overexpression of mutant,
      but not wild-type, PS1 selectively increases brain A beta42(43). These results
      indicate that the presenilin mutations probably cause Alzheimer's disease through
      a gain of deleterious function that increases the amount of A beta42(43) in the
      brain.

PMID- 8878480
TI  - Hippocampal synaptic transmission enhanced by low concentrations of nicotine.
AB  - Nicotine obtained from tobacco can improve learning and memory on various tasks
      and has been linked to arousal, attention, rapid information processing, working
      memory, and long-term memories that can cause craving years after someone has
      stopped smoking. One likely target for these effects is the hippocampus, a centre
      for learning and memory that has rich cholinergic innervation and dense nicotinic
      acetylcholine receptor (nAChR) expression. During Alzheimer's dementia there are
      fewer nAChRs and the cholinergic inputs to the hippocampus degenerate. However,
      there is no evidence for fast synaptic transmission mediated by nAChRs in the
      hippocampus, and their role is not understood. Nicotine is known to act on
      presynaptic nAChRs within the habenula of chick to enhance glutamatergic
      transmission; here we report that a similar mechanism operates in the
      hippocampus. Measurements of intracellular Ca2+ in single mossy-fibre presynaptic
      terminals indicate that nAChRs containing the alpha7 subunit can mediate a Ca2+
      influx that is sufficient to induce vesicular neurotransmitter release. We
      propose that nicotine from tobacco influences cognition by enhancing synaptic
      transmission. Conversely, a decreased efficacy of transmission may account for
      the deficits associated with the loss of cholinergic innervation during
      Alzheimer's disease.

PMID- 8878481
TI  - Death of oligodendrocytes mediated by the interaction of nerve growth factor with
      its receptor p75.
AB  - Members of the nerve growth factor (NGF) family promote the survival of neurons
      during development. NGF specifically activates the receptor trkA, initiating a
      signal transduction cascade which ultimately blocks cell death. Here we show that
      NGF can have the opposite effect, inducing the death of mature oligodendrocytes
      cultured from postnatal rat cerebral cortex. This effect was highly specific,
      because NGF had no effect on oligodendrocyte precursors and astrocytes. Other
      neurotrophins such as brain-derived neurotrophin factor (BDNF) and neurotrophin-3
      (NT-3) did not induce cell death. NGF binding to mature oligodendrocytes
      expressing the p75 neurotrophin receptor, but not trkA, resulted in a sustained
      increase of intracellular ceramide and c-Jun amino-terminal kinase (JNK)
      activity, which are thought to participate in a signal transduction pathway
      leading to cell death. Taken together, these results indicate that NGF has the
      ability to promote cell death in specific cell types through a ligand-dependent
      signalling mechanism involving the p75 neurotrophin receptor.

PMID- 8878482
TI  - Cytomegalovirus selectively blocks antigen processing and presentation of its
      immediate-early gene product.
AB  - Recognition of virus-infected cells by CD8+ cytotoxic T lymphocytes requires that
      the viral proteins be processed into peptides, the derived peptides transported
      into the endoplasmic reticulum and inserted into the binding groove of a major
      histocompatibility complex class I molecule, and the antigenic complex exported
      to the cell surface. However, viral pathogens can disrupt this process and
      interfere with immune recognition. These mechanisms may be vital to large viruses
      such as human cytomegalovirus (CMV), which causes persistent infection despite
      producing over 200 potentially antigenic proteins during the sequential immediate
      early, early and late phases of viral gene expression. Products of CMV early
      phase gene expression can globally block class I presentation and prevent
      recognition of infected cells by cytotoxic T lymphocytes, but an essential viral
      transcription factor, the 72K principal immediate-early protein, is abundantly
      expressed before this blockade. However, only a few host CD8+ cytotoxic T
      lymphocytes specific for immediate-early protein are present in seropositive
      individuals, and these lyse CMV-infected cells poorly. Here we demonstrate
      selective abrogation of immediate-early peptide presentation by a CMV matrix
      protein with associated kinase activity and suggest that modification of a viral
      protein can result in limiting access to the processing machinery and evasion of
      cytotoxic-T-cell recognition.

PMID- 8878483
TI  - Bidirectional signalling through the EPH-family receptor Nuk and its
      transmembrane ligands.
AB  - Receptor tyrosine kinases of the EPH class have been implicated in the control of
      axon guidance and fasciculation, in regulating cell migration, and in defining
      compartments in the developing embryo. Efficient activation of EPH receptors
      generally requires that their ligands be anchored to the cell surface, either
      through a transmembrane (TM) region or a glycosyl phosphatidylinositol (GPI)
      group. These observations have suggested that EPH receptors can transduce signals
      initiated by direct cell-cell interaction. Genetic analysis of Nuk, a murine EPH
      receptor that binds TM ligands, has raised the possibility that these ligands
      might themselves have a signalling function. Consistent with this, the three
      known TM ligands have a highly conserved cytoplasmic region, with multiple
      potential sites for tyrosine phosphorylation. Here we show that challenging cells
      that express the TM ligands Elk-L or Htk-L with the clustered ectodomain of Nuk
      induces phosphorylation of the ligands on tyrosine, a process that can be
      mimicked both in vitro and in vivo by an activated Src tyrosine kinase. Co
      culture of cells expressing a TM ligand with cells expressing Nuk leads to
      tyrosine phosphorylation of both the ligand and Nuk. These results suggest that
      the TM ligands are associated with a tyrosine kinase, and are inducibly
      phosphorylated upon binding Nuk, in a fashion reminiscent of cytokine receptors.
      Furthermore, we show that TM ligands, as well as Nuk, are phosphorylated on
      tyrosine in mouse embryos, indicating that this is a physiological process. EPH
      receptors and their TM ligands therefore mediate bidirectional cell signalling.

PMID- 8878484
TI  - Functional interactions between Stat5 and the glucocorticoid receptor.
AB  - Signal transduction pathways enable extracellular signals to activate latent
      transcription factors in the cytoplasm of cells. Dimerization, nuclear
      localization and binding to specific DNA sequences result in the induction of
      gene transcription by these proteins. These events are necessary for the
      functioning of the JAK/STAT pathway and of the glucocorticoid-receptor pathway.
      In the former, the protein Stat5, which is a member of a family of signal
      transducers and activators of transcription, is activated by cytokines, hormones
      and growth factors. These polypeptide ligands bind at the outside of the cell to
      specific transmembrane receptors and activate intracellular Janus protein
      tyrosine kinases (JAKs) to tyrosine-phosphorylate STAT proteins; interaction with
      the SH2 domain of the dimerization partner then confers the ability to bind to
      DNA at the STAT-response element and induce transcription. In the glucocorticoid
      receptor pathway, the receptor interacts with its steroid hormone ligand in the
      cytoplasm, undergoes an allosteric change that enables the hormone receptor
      complex to bind to specific DNA-response elements (glucocorticoid response
      elements, or GRE) and modulate transcription. Although these pathways appear to
      be unrelated, we show here that the glucocorticoid receptor can act as a
      transcriptional co-activator for Stat5 and enhance Stat5-dependent transcription.
      Stat5 forms a complex with the glucocorticoid receptor which binds to DNA
      independently of the GRE. This complex formation between Stat5 and the
      glucocorticoid receptor diminishes the glucocorticoid response of a GRE
      containing promoter.

PMID- 8878485
TI  - An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha.
AB  - Cholesterol and its oxysterol congeners are important constituents of cell
      membranes and function as intermediates in several crucial biosynthetic pathways.
      These compounds autoregulate their metabolic fate by end-product repression and
      activation of downstream catabolism. Although end-product repression by
      oxysterols is relatively well understood, the mechanism by which these compounds
      act as positive transcription signalling molecules is unknown. Here we identify a
      specific group of endogenous oxysterols that activate transcription through the
      nuclear receptor LXR alpha. Transactivation of LXR alpha by oxysterols occurs at
      concentrations at which these compounds exist in vivo. The most potent activators
      also serve as intermediary substrates in the rate-limiting steps of three
      important metabolic pathways: steroid hormone biosynthesis, bile acid synthesis,
      and conversion of lanosterol to cholesterol. Our results demonstrate the
      existence of a nuclear receptor signalling pathway for oxysterols and suggest
      that LXR alpha may be important as a sensor of cholesterol metabolites.

PMID- 8878486
TI  - Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA
      guides.
AB  - Eukaryotic ribosomal RNAs are post-transcriptionally modified by methylation at
      the ribose sugar of specific nucleotides. This takes place in the nucleolus and
      involves a family of small nucleolar RNAs (snoRNAs) with long regions (10-21
      nucleotides) complementary to rRNA sequences spanning the methylation site--a
      complementary snoRNA is required for methylation at a specific site. Here we show
      that altering the sequence of the snoRNA is sufficient to change the specificity
      of methylation. Mammalian cells transfected with a snoRNA engineered to be
      complementary to an arbitrary rRNA sequence direct the methylation of the
      predicted nucleotide in that sequence. We have further identified structural
      features, both of the guide and substrate RNA, required for methylation and have
      used these to design an exogenous transcript, devoid of rRNA sequence, that is
      site-specifically methylated when coexpressed with an appropriate guide snoRNA.
      Endogenous non-ribosomal RNA can thus be targeted, possibly providing a highly
      selective tool for the alteration of gene expression at the post-transcriptional
      level.

PMID- 8878487
TI  - A new class of uracil-DNA glycosylases related to human thymine-DNA glycosylase.
AB  - Mispairs in DNA of guanine with uracil and thymine can arise as a result of
      deamination of cytosine and 5-methylcytosine, respectively. In humans such
      mispairs are removed by thymine-DNA glycosylase (TDG). By deleting the carboxy
      and amino termini of this enzyme we have identified a core region capable of
      processing G/U but not G/T mispairs. We have further identified two bacterial
      proteins with strong sequence homology to this core and shown that the homologue
      from Escherichia coli (dsUDG) can remove uracil from G/U mispairs. This enzyme is
      likely to act as a back-up to the highly efficient and abundant enzyme uracil-DNA
      glycosylase (UDG) which is found in most organisms. Pupating insects have been
      reported to lack UDG activity, but we have identified an enzyme similar to dsUDG
      in cell lines from three different insect species. These data imply the existence
      of a family of double-strand-specific uracil-DNA glycosylases which, although
      they are subservient to UDG in most organisms, may constitute the first line of
      defence against the mutagenic effects of cytosine deamination in insects.

PMID- 8878488
TI  - Going to work in genes catches on.

PMID- 8878489
TI  - Counselling comes of age.

PMID- 8878490
TI  - Tough competition in Europe.

PMID- 8878491
TI  - Here come tomorrow's millionaires.

PMID- 8878492
TI  - Germans learn to bet on biotech.

PMID- 8878493
TI  - Inpatient vs. outpatient bowel preparation for elective colorectal surgery.
AB  - BACKGROUND: Recent pressures to decrease the cost of medical care have mandated
      preoperative outpatient bowel preparation (OBP) for elective colorectal surgery
      without any data documenting equivalent quality of care. This study examined the
      safety and efficacy of OBP compared with inpatient bowel preparation (IBP).
      METHODS: Records of all patients who underwent OBP for elective colorectal
      resection since the inception of the OBP program from July 1993 to June 1994 were
      compared with records of all patients who received IBP for elective procedures
      from January to June 1993. RESULTS: The two groups, 90 patients who underwent OBP
      and 98 patients who had IBP, were well matched for age, sex, diagnosis, and
      operations performed. The OBP group had a shorter length of hospital stay
      (median, 7 vs. 9 days; P < 0.0001; chi-squared analysis), whereas the
      complication rate was similar (19 percent in the OBP group vs. 18 percent in the
      IBP group), including infectious complications (10 percent in the OBP group vs. 7
      percent in the IBP group). Although operating time was similar (mean, 199 vs. 213
      minutes) and estimated blood loss (mean, 528 vs. 536 ml), the OBP group had
      significantly higher perioperative fluid requirements: intraoperative fluids
      (median, 4300 vs. 3700 ml; P < 0.05; Student's t-test), intraoperative colloid
      administration (48 vs. 29 percent; P < 0.0002; chi-squared), 24-hour
      postoperative fluids (3224 vs. 2700 ml; P < 0.0001; Student's t-test), and
      postoperative fluid challenges (50 vs. 20 percent; P < 0.0001; chi-squared
      analysis). CONCLUSION: Outpatient bowel preparation for elective colorectal
      surgery is safe and effective. It offers shorter hospital stay, and, therefore,
      potentially reduces medical care cost. Patients with multiple medical problems
      may not tolerate extensive fluid shifts; therefore, other preoperative
      arrangements, such as inpatient or outpatient intravenous fluid therapy, need to
      be considered to minimize complications that may outweigh potential cost savings.

PMID- 8878494
TI  - Excellent outcome using selective criteria for rectocele repair.
AB  - PURPOSE: The aim of this study was to review our experience with patients with
      rectoceles using very selective criteria for operative repair and to critically
      review our surgical results. METHODS: This is a review of patients selected for
      rectocele repair between 1989 and 1994. RESULTS: Two hundred seventy-nine
      patients were evaluated for pelvic outlet symptoms in our clinic. Defecography
      was performed in 180 patients; rectocele was seen in 143 patients (79 percent;
      135 females and 8 males). On physical examination, 132 patients had a palpable
      rectocele (73 percent). Rectocele repair was recommended for 35 patients (13
      percent); 33 (32 females and 1 male) underwent this procedure. Mean age was 55
      (range, 16-78) years. Although many patients complained of constipation,
      incontinence and pelvic pain, in these 33 patients criteria for repair included
      the sensation of a vaginal mass or bulge that required digital support and/or
      rectal digitizing for evacuation (58 percent), retention of barium in the
      rectocele on defecography (55 percent), or a very large rectocele with internal
      anterior rectal wall prolapse (6 percent). A hysterectomy had been performed
      previously in 47 percent of women repaired. Rectocele repair was performed by a
      standard transanal approach in 31 patients and transabdominally in 2 patients.
      Hospital stay averaged 3.7 (range, 1-8) days. Few postoperative complications
      occurred; urinary retention was the most common (18 percent). All patients were
      followed postoperatively, and 26 patients (79 percent) answered a standardized
      questionnaire. Mean follow-up was 31 (range, 5-64) months. Eighty percent of
      patients questioned who initially complained of a vaginal mass or bulge reported
      complete resolution (significant improvement by the sign test, P < 0.5).
      Subjectively, 92 percent of patients questioned reported improvement in their
      preoperative symptoms and satisfaction with the operation. CONCLUSION: Rectoceles
      are frequently identified during defecography, which is performed for pelvic
      floor complaints, yet are often asymptomatic. In contrast to other recent reports
      of rectocele repair, our data indicate that careful selection of patients using
      specific criteria may result in very good clinical results.

PMID- 8878495
TI  - Photodynamic therapy of colorectal cancer using a new light source: from in vitro
      studies to a patient treatment.
AB  - PURPOSE: Photodynamic therapy (PDT) is a relatively new alternative modality for
      palliation of rectal cancer. Current source of light for PDT are laser systems
      that are expensive and not necessarily needed for PDT. We evaluated a new
      nonlaser light source for PDT, Versa-Light. METHODS AND RESULTS: In vitro PDT-
      CT26 murine colon carcinoma cells were incubated with aluminum phthalocyanine
      (AlPcS4) for 48 hours and subjected to photoradiation using Versa-Light, and
      viability was assessed. There was a significant decrease in viability of treated
      cells compared with controls. In vivo PDT--BALB/c mice were injected either
      subcutaneously or intrarectally with CT26 cancer cells. IP AlPcS4 (2.5 mg/kg) was
      injected when tumors were visible. After 24 hours, mice were subjected to
      photoradiation. Massive tumor necrosis in response to PDT was observed. PDT also
      prolonged survival of treated mice. Patient treatment--A 70-year-old woman with
      recurrent local rectal carcinoma received intravenous Photofrin II (2 mg/kg).
      After 48 and 96 hours, she was subjected to direct photoradiation. After the
      first light session, there was complete macroscopic disappearance of the tumor.
      Biopsies up to 10 weeks after the treatment showed no cancer cells in the treated
      area. Sixteen weeks later, a randomized biopsy from previous tumor site showed
      carcinoma cells. CONCLUSIONS: We believe that Versa-Light, is a good light source
      for PDT. It was effective in both in vitro and animal studies. It can also be
      safely used for clinical PDT.

PMID- 8878496
TI  - Changing causes of mortality in patients with familial adenomatous polyposis.
AB  - Widespread use of prophylactic colectomy has resulted in a reduction in the
      incidence of colorectal cancer in familial adenomatous polyposis (FAP) patients.
      A retrospective chart review of families registered at the Steve Atanas Stavro
      Familial Gastrointestinal Cancer Registry in Toronto was performed to determine
      whether the decrease in the number of patients developing colorectal cancer
      implies that causes of mortality in FAP patients are shifting to that of
      extracolonic manifestations of FAP. Information was available on 140 deaths
      within 158 families and among 461 individuals with FAP. When stratified by
      decade, from the 1930s to the 1990s, the ratio of deaths caused by extracolonic
      manifestations of FAP compared with deaths caused by colorectal cancer was noted
      to have risen. Even though most deaths in FAP patients are still from colorectal
      cancer, it appears that screening policies and prophylactic colectomy have
      resulted in a reduction in the number of FAP patients who develop colorectal
      cancer. Thus, in recent decades, a greater percentage of deaths in FAP patients
      appears to be attributable to extracolonic manifestations of the disease.

PMID- 8878497
TI  - Surveillance of colorectal cancer: effectiveness of early detection of
      intraluminal recurrences on prognosis and survival of patients treated for cure.
AB  - PURPOSE: The authors evaluate the effectiveness of routine colonoscopy and marker
      evaluation in diagnosis of intraluminal recurrent cancer. METHODS: Chart review
      was conducted on 481 patients who underwent curative resection for colorectal
      cancer between 1980 and 1990. Clinical visits were scheduled and carcinoembryonic
      antigen evaluation was performed every three months, and colonoscopy was
      performed preoperatively, 12 to 15 months after surgical treatment, and then with
      intervals of 12 to 24 months or when symptoms appeared. RESULTS: About 10 percent
      of patients developed intraluminal recurrences. More than one-half of
      metachronous lesions arose within the first 24 months, and median time to
      diagnosis was 25 months. Patients with left-sited tumors in the advanced stage
      had a higher risk of developing recurrent intraluminal disease. Twenty-nine
      patients underwent a second surgical operation, of which 17 cases were radical.
      In this group, the five-year survival was 70.6 percent, although no nonradically
      treated or nonresected patients survived longer than 31 months. Twenty-two
      patients were asymptomatic at time of diagnosis of recurrence, and of these, 12
      patients underwent radical operation; on the other hand, of the 24 symptomatic
      patients, only 5 were treated radically. Carcinoembryonic antigen was the first
      sign of recurrence in eight cases. Colonoscopy must be performed within the first
      12 to 15 months after operation, whereas an interval of 24 months between
      examinations seems sufficient to guarantee early detection of metachronous
      lesions. CONCLUSION: Serial tumor marker evaluation is of help in earlier
      diagnosis of local recurrences. Asymptomatic patients more frequently undergo
      another operation for cure and thus have a better survival rate.

PMID- 8878498
TI  - Tuberculous peritonitis--do not miss it.
AB  - Incidence of tuberculosis is sharply rising in the United States, and tuberculous
      peritonitis is often diagnosed late in the course of the disease, resulting in
      undue patient morbidity and mortality. PURPOSE: Purpose of this study was to
      better identify which clinical, laboratory, radiologic, and invasive procedures
      were most useful in diagnosing tuberculous peritonitis. METHODS: All cases of
      tuberculous peritonitis diagnosed between 1982 and 1994 were reviewed
      retrospectively to discern which laboratory, radiographic, and procedural tests
      were helpful in diagnosing the condition. RESULTS: Twenty-eight cases of
      tuberculous peritonitis were diagnosed during the studied period. Two patients
      were not diagnosed until autopsy. Patients from all socioeconomic classes and
      multiple races ranged in age from 3 to 69 (mean, 29.5) years. Most patients
      presented with a chronic wasting illness, mild abdominal pain, and fever.
      Purified protein derivative was only positive in 5 of 16 patients. Chest
      radiographs were suggestive of pulmonary tuberculosis (TB) in five patients.
      Ultrasound examination of the abdomen was helpful in five patients, and computed
      tomographic scan was suspicious in 16 of 17 patients. Sputum for acid fast
      bacillus (AFB) smear was positive in 3 of 14 patients, and paracentesis for AFB
      smear was positive in 1 of 8 patients. Routine blood work was not helpful.
      Laparoscopy was diagnostic in five of seven patients. Laparotomy and tissue
      biopsy of characteristic tissue for AFB smear and culture was diagnostic in 20 of
      20 patients. Once diagnosed, all patients responded rapidly to empiric
      antituberculous medical therapy, except one patient with miliary TB who died
      shortly after diagnosis. A trend in earlier diagnosis was noted in recent years
      and is felt to be the result of an elevated index of suspicion. CONCLUSIONS: TB
      peritonitis may be fatal but is medically cured if diagnosed in a timely fashion.
      It is essential that the clinician suspect the disease in appropriate patients.
      Tests frequently associated with TB such as chest radiograph and purified protein
      derivative are not sensitive in detection of TB peritonitis. Computed tomographic
      scan is the most useful radiographic study. Mini laparotomy with tissue biopsy
      for smear and culture is the most sensitive and specific diagnostic procedure.

PMID- 8878499
TI  - Lack of correlation of anorectal manometry with symptoms of chronic childhood
      constipation and encopresis.
AB  - Chronic constipation is an extremely common problem in children. Many authors
      have advocated using anorectal manometric examination during evaluation of
      chronic childhood constipation and encopresis as a means of developing
      individualized modes of treatment. PURPOSE: This study was designed to
      prospectively examine frequency and severity of symptoms of childhood
      constipation and encopresis and associate these symptoms with anorectal
      manometric findings. METHODS: Forty-four children with chronic constipation
      participated in the study. Before performing anorectal manometry, bowel-related
      symptoms were collected for two consecutive weeks with a computerized voice mail
      system. Anorectal manometry was performed using a triple lumen catheter attached
      to a hydraulic manometry infusion system. RESULTS: Frequency of voluntary bowel
      movements did not correlate with any manometric parameters. Frequency of fecal
      soiling, age at onset of symptoms, and duration of symptoms were all highly
      correlated with degree of sphincter spasm during attempted defecation; however,
      none of these variables correlated with any other manometric parameter. Amount of
      pain associated with bowel movements correlated with frequency of soiling and was
      inversely correlated with maximum squeeze pressure but was not correlated with
      any other manometric parameter. CONCLUSIONS: In children with chronic
      constipation and encopresis, sphincter spasm demonstrated with anorectal
      manometry is highly correlated with frequency of fecal soiling, age at onset, and
      duration of symptoms; however, none of the other commonly measured manometric
      parameters appear to correlate with symptoms of chronic childhood constipation
      and encopresis.

PMID- 8878500
TI  - Androgen induces ornithine decarboxylase gene expression in colonic cell line HT
      29.
AB  - Carcinoma of the colon is the second most common cancer among men and women
      combined in the United States. PURPOSE: Ornithine decarboxylase (ODC) is the
      first and key regulatory enzyme in the polyamine biosynthesis pathway and is
      regulated by various factors. Polyamines are believed to participate in cellular
      proliferation and differentiation. High levels of polyamines and ODC activity are
      associated with rapid cell growth, particularly in tumor tissues. Regulation of
      this enzyme in vivo has important clinical implications. In the present study, we
      used Northern analysis and mobility shift assay to investigate whether ODC gene
      expression is regulated by androgens in the three human colonic cell lines,
      SW620, HT-29, and Caco-2. METHODS: Cell lines were maintained in Dulbecco's
      Modified Eagle's medium/F12 supplemented with 5 percent fetal bovine serum. At 60
      percent confluency, medium was replaced with steroid-depleted medium, and
      incubation continued for 24 hours. Following this period, medium was replaced
      with fresh steroid-free medium containing 1 nM dihydrotestosterone. RESULTS:
      Dihydrotestosterone stimulated ODC messenger ribonucleic acid expression only in
      HT-29 colonic cell line. Studies using electrophoretic mobility shift assays of
      nuclear extracts also showed a binding pattern with SP1 and NF-kappaB regulatory
      sequences only in testosterone-treated HT-29 cells. CONCLUSION: These results
      suggest that androgens may play an important role in the growth of HT-29 colonic
      cell lines.

PMID- 8878501
TI  - Electrophysiologic assessments in pudendal and sacral motor nerves after ileal J
      pouch-anal anastomosis for patients with ulcerative colitis and adenomatosis
      coli.
AB  - PURPOSE: To clarify neurologic function with respect to external anal sphincter
      and puborectalis muscles after J configuration ileal J-pouch-anal anastomosis for
      patients with ulcerative colitis and adenomatosis coli, we examined the terminal
      motor latency in the pudendal and sacral motor nerve (S2-4). METHODS: Latency of
      the response in the external anal sphincter muscle following digitally directed
      transrectal pudendal nerve stimulation (PNTML) and in the puborectalis muscle
      following transcutaneous magnetic stimulation of the cauda equina at the levels
      S2-4 (SMNLTSS) were measured in 12 patients with ileal J-pouch-anal anastomosis;
      they were divided into a group with continence (7 cases) and a group with soiling
      (5 cases). Results were compared with data obtained from 12 patients before
      operation and 15 controls. RESULTS: Conduction delay of PNTML and SMNLTSS in
      patients with soiling was longest, followed by delay in those without any
      soiling, then delay in patients before operation, and then controls. In addition,
      significant differences were also noted between conduction delay of PNTML in
      controls and those who are incontinent and experience soiling (P < 0.05 and P <
      0.01, respectively), and there were significant differences also noted between
      conduction delay of PNTML in patients before operation and those who are
      incontinent and experiencing soiling (P < 0.05 and P < 0.01, respectively).
      Conduction delay of PNTML and SMNLTSS were found in patients before operation
      rather than in controls. No significant differences were noted between conduction
      delay of PNTML and SMNLTSS in patients before operation and controls. Significant
      differences were also noted between conduction delay of PNTML and SMNLTSS in
      patients who are incontinent and experiencing soiling (P < 0.01, respectively).
      CONCLUSION: These findings support the hypothesis that soiling after this
      procedure may be partially caused by damage to pudendal and sacral motor nerves
      (S2-4).

PMID- 8878503
TI  - Endoscopic dilation of rectal strictures: a prospective study of 18 cases.
AB  - PURPOSE: This study was performed to prospectively evaluate results of endoscopic
      balloon dilation of strictures of the rectum. METHODS: Eighteen patients with
      symptoms of rectal strictures at endoscopy or barium enema were treated on 49
      occasions with balloon dilation during sigmoidoscopy. RESULTS: Twelve patients
      were completely satisfied with relief of their symptoms after treatment. Two
      patients considered the results as poor, and four patients were not subject to
      follow-up evaluation. One patient had a perforation during the dilation procedure
      but was completely relieved at follow-up examination. CONCLUSIONS: Endoscopic
      balloon dilation of strictures in the rectum is a safe method. The method is
      simple and can be performed on an outpatient basis. The technique shows good
      results even in narrow strictures.

PMID- 8878502
TI  - Clinical evaluation of chemosensitivity testing for patients with colorectal
      cancer using MTT assay.
AB  - PURPOSE: Colorectal cancer is one of the tumors most refractory to treatment by
      chemotherapy. The chemosensitivity test should be performed to individualize the
      chemotherapy for patients with colorectal cancer, which is less sensitive for
      anticancer drugs. The present study was designed to determine the
      chemosensitivity in fresh human colorectal cancer, using highly purified tumor
      cells, and the correlation of this sensitivity with clinical response. METHODS:
      We determined the chemosensitivity for cisplatin, mitomycin C, adriamycin, and 5
      fluorouracil in vitro in 93 fresh human colorectal cancers using the MTT assay
      and performed chemotherapy according to results of the MTT assay. RESULTS:
      Inhibition rate of tumor cells for cisplatin was higher than those for other
      drugs. Fifteen patients who have evaluable lesions received chemotherapy
      according to results of the MTT assay. Clinical responses were obtained in 5 of
      15 patients, and the inhibition rate for cisplatin was higher in responders than
      in nonresponders. CONCLUSIONS: It is suggested that the chemotherapy according to
      results of the MTT assay is effective in patients with colorectal cancer.

PMID- 8878504
TI  - Relationship of curative surgery on natural killer cell activity in colorectal
      cancer.
AB  - PURPOSE: Aim of this study has been to evaluate natural killer (NK) activity in
      patients with colorectal tumors before and after curative surgery. METHODS: Forty
      colorectal cancer patients without distant metastases were stratified according
      to American Joint Committee on Cancer/International Union Against Cancer staging
      system into three categories: Stage I (n = 12), Stage II (n = 15), and Stage III
      (n = 13). All of them underwent curative resection, and there were no major
      postoperative complications. Venous blood samples were obtained preoperatively,
      at surgical wound closure, and on the 1st, 7th, and 21st postoperative days.
      Mononuclear cells were isolated over Ficoll-Hypaque (Lymphoprep, Nycomed Pharma
      AS, Oslo, Norway) gradients, and NK activity was assayed by evaluation of
      cytotoxic response against K562 cells. Normal NK activity was achieved from 15
      healthy donors. Percentage relative increments in relation to preoperative levels
      were calculated for every postoperative sample, and t-test was used for
      statistical evaluation. RESULTS: Before surgery, Stages II and III patients had
      lower levels of NK activity than healthy people (P < 0.05 and P < 0.001,
      respectively). NK activity always fell after surgery (Stage I: -18.48 +/- 11.42;
      Stage II: -16.93 +/- 13.57; Stage III: -35.29 +/- 12.03, at day 1 postsurgery)
      and appeared to rise slightly by the 21st postoperative day in Stage I patients
      (+4.87 +/- 12.41). Stage II, and especially Stage III, patients did show a
      significant recovery by the 21st postoperative day (+23.63 +/- 9.36 and +43.19 +/
      13.34, respectively). At this time, NK activity in these two groups was not
      significantly lower than in normal subjects (P > 0.05). CONCLUSION: NK activity
      is depressed in colorectal cancer patients in relation to progression of illness,
      even at locoregional stages. Curative resection of tumors at Stages II and III
      has promoted a recovery of NK activity in patients with uneventful postoperative
      courses.

PMID- 8878505
TI  - The anal sphincter in idiopathic megarectum: effects of manual disimpaction under
      general anesthetic.
AB  - PURPOSE: This study was designed to investigate the function and morphology of
      anal sphincters in patients with an idiopathic megarectum. METHOD: A total of 17
      patients were studied by anal endosonography and manometry when not impacted.
      Fourteen had previously been manually disimpacted under general anesthetic, and
      three had not. RESULTS: Nine of 14 patients in the former group, but none of the
      latter group, had disruption of one or both anal sphincter muscles on
      endosonography. Endosonographic changes were characteristic of those identified
      previously in patients following anal dilation. Low anal resting pressure,
      indicative of internal sphincter dysfunction, was found in a substantial
      proportion of patients with either an endosonographically intact or disrupted
      internal anal sphincter. Voluntary contraction increment, a reflection of
      external sphincter function, was normal in all patients. CONCLUSION: Manual
      disimpaction under general anesthetic appears to be associated with iatrogenic
      structural injury to the anal sphincters. In some patients, this may contribute
      to sphincter weakness. This damage may contribute to the incontinence experienced
      by patients with a dilated rectum.

PMID- 8878506
TI  - Open vs. closed sphincterotomy for chronic anal fissure: long-term results.
AB  - PURPOSE: This study was undertaken to compare the healing rate and long-term
      effects on continence of open and closed lateral internal sphincterotomy.
      METHODS: Charts of 864 patients with chronic anal fissure who underwent internal
      sphincterotomy as a single procedure over five years by a group of 12 colorectal
      surgeons were reviewed. Open internal sphincterotomy (OIS) was performed in 521
      patients, whereas 343 had closed internal sphincterotomy (CIS). There was no
      difference in sex or age between the groups. A questionnaire inquiring about
      clinical outcome, changes in continence, and degree of satisfaction with the
      procedure was mailed to all patients. A total of 549 (63.5 percent) patients, 324
      (62.2 percent) with OIS and 225 (65.6 percent) with CIS, returned their
      questionnaires. Average follow-up was three (range, 1-6) years. RESULTS:
      Differences in persistence of symptoms (3.4 OIS vs. 5.3 percent CIS), recurrence
      of the fissure (10.9 vs. 11.7 percent CIS), and need for reoperation (3.4 percent
      OIS vs. 4 percent CIS) were statistically not significant. However, statistically
      significant differences were seen in the percentage of patients with permanent
      postoperative difficulty controlling gas (30.3 vs. 23.6 percent; P 0.062),
      soiling underclothing (26.7 vs. 16.1 percent; P < 0.001), and accidental bowel
      movements (11.8 vs. 3.1 percent; P < 0.001) between those who underwent OIS and
      those who had CIS. Although 90 percent of patients reported general overall
      satisfaction, more patients undergoing CIS (64.4 percent) than OIS (49.7 percent)
      were very satisfied with the results of the procedure. CONCLUSIONS: Lateral
      internal sphincterotomy is highly effective in treatment of chronic anal fissure
      but is associated with significant permanent alterations in continence. CIS is
      preferable to OIS because it effects a similar rate of cure with less impairment
      of control.

PMID- 8878507
TI  - Surgery for constipation: a review.
AB  - PURPOSE: Constipation is related to intestinal motility disorders (colonic
      inertia (CI)), pelvic floor disturbances (pelvic outlet obstruction), or a
      combination of both problems. This review summarizes the physiologic and
      pathophysiologic changes in patients with intractable constipation and gives an
      overview of surgical treatment options. RESULTS: Although subtotal colectomy with
      ileorectal anastomosis is the best surgery for CI, there are still approximately
      10 percent of patients who will complain of pain and constipation. A completion
      proctectomy and an ileoanal pouch procedure may be a viable option in a highly
      select group of patients. In patients with megabowel, reported results are mixed.
      Subtotal colectomy, partial colectomy for megacolon, and the Duhamel procedure
      for megarectum have all been reported with variable results. In patients with an
      isolated distended sigmoid colon, sigmoid colectomy has achieved good results.
      Anorectal myectomy has not been proven to be successful in the long term.
      However, in patients with adult short segment Hirschsprung's disease, myectomy
      can be successful. Patients with pelvic outlet obstruction can be successfully
      treated with biofeedback. In a small group of patients with a rectocele or a
      third degree sigmoidocele, surgical intervention yields a high success rate.
      Division or resection of the puborectalis muscle is not recommended. In patients
      with a mixed pattern of CI and pelvic outlet obstruction, surgical intervention
      alone is often not successful. These patients achieve better results by
      conservative treatment of pelvic outlet obstruction, followed by a colectomy.
      CONCLUSION: Surgical intervention for patients with intractable constipation is
      rarely necessary. However, thorough preoperative physiologic testing is mandatory
      for a successful outcome.

PMID- 8878508
TI  - Technique for atraumatic delivery of intestine through the abdominal wall during
      stoma formation.
AB  - A technique to minimize injury to the bowel and its associated mesentery during
      difficult stoma creation is presented. A penrose drain is used to ensheathe the
      terminal segment of bowel, creating a uniform "tube" of intestine, protecting and
      facilitating delivery of the bowel through the abdominal wall.

PMID- 8878509
TI  - New option for recurrent rectovaginal fistulas.
AB  - PURPOSE: To describe an operative technique for repair of recurrent rectovaginal
      fistulas. METHODS: A diamond-shaped cutaneous flap advancement into the vagina
      and a standard endoanal advancement flap are described for use as an alternative
      option in treatment of recurrent rectovaginal fistulas. RESULTS: Complete healing
      of fistula was achieved with no impairment of continence. CONCLUSION: This
      technique is suitable in treatment of recurrent rectovaginal fistulas especially
      in frail and elderly patients.

PMID- 8878510
TI  - Fecal incontinence after pelvic radiotherapy: evidences for a lumbosacral
      plexopathy. Report of a case.
AB  - PURPOSE: Clinical manifestations of radiation-induced lumbosacral plexopathy
      remain a rare event. We report the case of a 62-year-old woman with neurogenic
      fecal incontinence that occurred after radiotherapy of cervical carcinoma.
      METHODS: Anorectal, bladder, and lower limb sensory-motor functions, as biologic
      and morphologic explorations, were performed on repeated occasions. RESULTS:
      Anorectal manometry, conduction times of pudendal nerves, sacral latencies, and
      pudendal nerve-evoked corticals disclosed lesions of the lumbosacral plexus that
      was confirmed by bladder manometry and electromyography of lower limbs. Biologic
      and morphologic explorations were within normal ranges. CONCLUSION: Because no
      other cause except radiation was demonstrated in this case, we suggest that
      plexopathy may be a late-occurring complication of radiotherapy.

PMID- 8878511
TI  - Perineal and perirectal sarcomas: report of two cases.
AB  - PURPOSE: Perineal sarcomas are rare tumors that are typically of an extensive
      nature by the time of diagnosis. In this article, two case reports are followed
      by a brief review of different types of sarcomas that may occur in the perineal
      and perirectal region. STUDY PATIENTS: This study consists of two cases that are
      representative of the many types of perineal/perirectal sarcomas. PRINCIPLE
      CONCLUSIONS: Perineal and perirectal sarcomas are generally of poor prognosis
      mainly because of delayed diagnosis. Computed tomography and magnetic resonance
      imaging can be extremely useful to help assess these tumors. It is well known
      that the most important criterion for diagnosing leiomyosarcomas appears to be
      the presence of mitotic activity. Anorectal stromal tumors having five or more
      mitoses per 50 high powered fields are considered to be malignant. The mainstay
      of treatment is surgical excision with wide margins. Currently, chemotherapeutic
      and radiotherapy trials are under way.

PMID- 8878512
TI  - Laparoscopic colectomy.

PMID- 8878513
TI  - TAG-72 expression in lymph nodes and RIGS.

PMID- 8878514
TI  - Disulfide bonds are necessary for structure and activity in Aspergillus ficuum
      phytase.
AB  - The function of disulfide bonds in Aspergillus ficuum phytase was elucidated by
      unfolding studies, using guanidinium hydrochloride (Gu.HCl) as denaturant.
      Although the enzyme is totally inactivated by 0.8 M Gu.HCl, at pH 5.0, the active
      conformation is instantaneously restored by 0.6 M Gu.HCl, at pH 5.0. Conditions
      which would permit refolding of phytase are completely negated by 10 mM beta
      mercaptoethanol and causes its catalytic demise at pH 7.5. Assay of free thiols
      using Ellman's reagent indicates that none of the thiols in the ten cysteines in
      phytase are free; five disulfide bonds were predicted for the enzyme. Sequence
      comparison of mold phytases and yeast acid phosphatases indicates four conserved
      cysteines. Thus, disulfide bonds play an important role in the folding of fungal
      phytase; any perturbation of the process of its formation causes an altered three
      dimensional structure that is inconsistent with catalytic activity.

PMID- 8878515
TI  - Effect of soluble interleukin-6 receptor on interleukin-6 synthesis in human skin
      fibroblasts.
AB  - In this study the ability of soluble interleukin-6 receptor (sIL-6R) to stimulate
      interleukin-6 (IL-6) synthesis in human fibroblasts is described. It was found
      that sIL-6R, in combination with endogenous or exogenous IL-6, markedly
      upregulated IL-6 synthesis. These data suggest that increased IL-6 production
      after stimulation by either interleukin-1 or tumor necrosis factor-alpha would
      result in complex formation with sIL-6R, rapid uptake, and further synthesis of
      this cytokine. Furthermore, it would explain the decrease in sIL-6R plasma levels
      observed in patients suffering from sepsis.

PMID- 8878516
TI  - Inhibitory effect of tranilast on activation and transforming growth factor beta
      1 expression in cultured rat stellate cells.
AB  - Stellate cells, the primary extracellular matrix-producing cells in the liver,
      undergo activation characterized by fibrogenesis, proliferation and smooth muscle
      alpha-actin expression, in hepatic fibrosis or when cultured on plastic. TGF beta
      1 is known to have a pivotal role in fibrogenesis. Tranilast, a drug used for
      allergic diseases with anti-inflammatory effects, is known to inhibit collagen
      synthesis by cultured fibroblasts. Thus, effects of tranilast on activation and
      TGF beta 1 expression in stellate cells was investigated in vitro. Tranilast
      reduced collagen synthesis in a dose-related manner up to 50.8% of the control.
      This effect was reversible after tranilast withdrawal. The mobility of
      procollagen on gel electrophoresis and the ratio of intracellular procollagen to
      extracellular collagen concentrations were not affected by tranilast. Tranilast
      decreased DNA synthesis and increased smooth muscle alpha-actin expression. mRNA
      expressions of procollagen and TGF beta 1 were reduced by tranilast. Tranilast
      with anti-fibrogenic and anti-inflammatory actions merits consideration as a
      candidate for therapeutic agent of hepatic fibrosis.

PMID- 8878517
TI  - S-methylisothiourea inhibits inducible nitric oxide synthase and improves left
      ventricular performance after acute myocardial infarction.
AB  - The contribution of increased inducible nitric oxide synthase (iNOS) activity to
      the development of left ventricular dysfunction after acute myocardial infarction
      (MI) was investigated New Zealand rabbits (n = 24) were randomly treated with
      either saline, S-methylisothiourea sulfate (SMT; selective iNOS inhibitor) or N
      omega-nitro-L-arginine (NOLA; non-isoform selective NOS inhibitor). Left
      ventricular hemodynamics and myocardial blood flow were measured before coronary
      occlusion and on postoperative day 3 (POD 3). MI resulted in left ventricular
      dysfunction and increased myocardial iNOS activity. SMT and NOLA significantly
      inhibited iNOS activity; SMT, but not NOLA, significantly improved left
      ventricular maximum +dP/dt and decreased LVEDP; myocardial blood flow in the
      remote myocardium significantly increased after SMT. Induction of myocardial iNOS
      after MI on POD 3 contributes to the development of left ventricular dysfunction;
      modulation of iNOS activity by SMT improves left ventricular performance and may
      be beneficial after acute MI.

PMID- 8878518
TI  - Mutagenic specificity of N-methyl-N'-nitro-N-nitrosoguanidine in the tonB gene on
      the chromosome of Escherichia coli recA+ and recA- cells.
AB  - DNA base sequence changes induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      mutagenesis has been determined for the endogenous tonB gene of Escherichia coli
      recA+ strain and its isogenic recA56 strain. In the recA+ strain, base
      substitutions accounted for 48 mutations among 54 MNNG-induced independent
      mutations analyzed and consisted of 45 G:C to A:T transitions, two A:T to G:C
      transitions and one A:T to C:G transversion. In the recA56 strain, 67% (34/51)
      were base substitutions among which G:C to A:T transition (28/51) predominated,
      followed by three A:T to T:A transversions, two G:C to T:A transversions, and one
      A:T to G:C transition. These mutagenic specificities were consistent with the
      mispairing predicted by the methylation of the O6 position of guanine. In both
      strains the G:C to A:T mutations were found at guanine residues preceded by
      either guanine or thymine on the non-transcribed strand of the target gene.

PMID- 8878519
TI  - A species comparison of chloral hydrate metabolism in blood and liver.
AB  - Chloral hydrate (CH), [302-17-0], is a human sedative useful in premature
      infants. No current epidemiological study supports increased cancer risk. CH is
      also a rodent toxicant and a P450-derived metabolite of trichloroethylene (TRI).
      P450 induction increases TRI toxicity in rodents. CH is very rapidly metabolized
      to trichloroacetic acid (TCA) and trichloroethanol (TCOH). Because TCA mediates
      some responses following TRI exposure, we assessed the metabolism of CH to TCA
      and TCOH by liver and blood of the rat, mouse, and human. Both TCA and TCOH are
      formed in blood and liver. The constants for hepatic TCA and TCOH formation are
      presented. The K(m) for hepatic TCOH formation is at least ten-fold lower than
      for TCA formation in these species. Clearance values for TCOH are higher than for
      TCA. These data support TCOH as the first major metabolite of TRI and CH in vivo.

PMID- 8878520
TI  - Effect of Ca2+ on the secondary structure of linear and cyclic collagen sequence
      analogs.
AB  - To investigate the role of secondary structure in the substrate specificity of
      human 72 kDa type IV collagenase, we synthesised linear and cyclic collagen
      sequence analogs. As Ca2+ plays a crucial role in the enzyme activity, the CD and
      FTIR spectra of the peptides were also measured in the presence of Ca2+. Most of
      the linear, but none of the cyclic peptides form stable 1:1 Ca2+ complexes. The
      cyclic hexapeptides adopt significantly different backbone conformations
      comprising not only beta-turns but also the less frequent gamma-turns.
      Consequently, in the cyclopeptides the scissile Gly-Ile(Leu) bond is embedded
      into a different conformational environment, but in spite of that none of them is
      a substrate or an inhibitor of the enzyme. The best substrate Ac-Pro-Leu-Gly-Leu
      Ala-Gly-D-Lys-OH binds Ca2+, but does not form a stable 1:1 Ca2+ complex, which
      suggests that instead of a folded structure an extended flexible conformation is
      preferred by the enzyme.

PMID- 8878521
TI  - Is there the creatine kinase equilibrium in working heart cells?
AB  - The mathematical model of the compartmentalised energy transfer system in cardiac
      myocytes, which includes mitochondrial synthesis of ATP by ATP-synthase,
      phosphocreatine production in the coupled mitochondrial creatine kinase reaction,
      the myofibrillar and cytoplasmic creatine kinase reactions, ATP utilisation by
      actomyosin ATPase during contraction cycle, and diffusional exchange of
      metabolites between different compartments, was used to calculate creatine kinase
      reaction rates (fluxes) in different cellular compartments at a workload
      corresponding to the rate of oxygen consumption of 46 micrograms-atom O2 *min-1 *
      (g wet mass)-1. The results of calculations showed that at this high workload all
      creatine kinase isoenzymes function most of their time in the cardiac cycle in
      the steady state far from equilibrium. This mathematical modelling shows that the
      validity of assumption of creatine kinase equilibrium is limited only to the
      diastolic phase of the contraction cycle in the working cardiac cells and only to
      the cytoplasmic compartment. In the systolic phase, due to rapid release of ADP
      at increased workloads, all creatine kinase isoenzymes are rapidly shifted out of
      the equilibrium. Cytoplasmic ADP concentration may increase up to 9 times in the
      systolic phase of the cardiac cycle, correspondingly changing all ADP-dependent
      parameters. Mitochondrial creatine kinase functions permanently in "metastable"
      steady state (Jurgen Daut, Biochim. Biophys. Acta 895, 41-62, 1987). It may be
      proposed that a more precise, in comparison to the equilibrium concept, way of
      calculating steady state cytoplasmic ADP concentrations at increased workloads is
      to use kinetic equations and mathematical models of energy metabolism.

PMID- 8878522
TI  - A hyperosmotic stimulus regulates intracellular pH, calcium, and S-100 protein
      levels in avian chondrocytes.
AB  - Cartilage is exposed to mechanical loads, generating at the level of single
      chondrocytes a hyperosmotic stimulus (HOS). The direct effect of HOS on second
      messenger pathways in avian chondrocytes was evaluated by fluorimetric and image
      analysis techniques. HOS caused an immediate intracellular acidification of 0.07
      +/- 0.02 pH units (n = 7), followed by an initial pH recovery rate of 0.033 +/-
      0.04 pH units/min towards the pre-stimulus baseline values. Concomitantly, the
      intracellular calcium ([Ca2+]i) responded with a transient rise from baseline
      value of 84.7 +/- 7.4 nM to peak level of 403.1 +/- 51.0 nM (n = 16, p < 0.001).
      The calcium response was abolished by two calmodulin inhibitors chlorpromazine
      and W-7. Since these inhibitors are known to be specific ligands of a S-100
      protein, its intracellular staining was determined following HOS. The amount of
      immunodetectable S-100 protein was significantly increased following exposure to
      HOS (p < 0.05), and did not require an increase of [Ca2+]i. It appears that
      compression of cartilage is transduced into HOS of chondrocytes, and further
      elicits its effects through transient intracellular elevation of protons and
      calcium ions accompanied by increased staining of S-100 protein.

PMID- 8878523
TI  - Protein and cDNA structures of an acidic phospholipase A2, the enzymatic part of
      an unusual, two-component toxin from Vipera palaestinae.
AB  - In the venom of Vipera palaestinae an unusual, two-component toxin was found. The
      two components of the toxin are an acidic phospholipase A2 (VpaPLA2) and a basic
      protein, both with an apparent molecular mass of about 15 kDa. Each component
      alone is not toxic; however, their mixture is lethal. We have determined the
      amino acid and cDNA sequences of VpaPLA2. The protein primary structure was
      solved by sequencing the peptides generated by chemical cleavage of the molecule
      using CNBr, formic acid and hydroxylamine-hydrochloride and by enzymatic
      fragmentation with trypsin and chymotrypsin. VpaPLA2 consists of 122 amino acid
      residues and has all the structural characteristics of subgroup IIA PLA2s. It
      shows the highest amino acid similarity to a non-toxic phospholipase A2 from
      Eristocophis macmahoni (82%), whereas the most similar toxic phospholipases A2
      share about 70% of residues with VpaPLA2. The substitution of His20 for a
      hydrophobic residue (Leu) in VpaPLA2 might be one of the reasons that its complex
      with the basic protein could not be observed.

PMID- 8878524
TI  - Inorganic lead activates NF-kappa B in primary human CD4+ T lymphocytes.
AB  - Inorganic lead (Pb) is a ubiquitous environmental contaminant that produces a
      variety of effects on humoral and cell mediated immune responses. The underlying
      molecular mechanism for Pb's complex effects on the immune system remain obscure.
      Many of Pb's effects on the immune system could be explained through activation
      of the transcription factor, NF-kappa B. NF-kappa B is critical for T lymphocyte
      function and is a strong inducer of HIV-LTR activation. We demonstrate that Pb at
      physiologically relevant concentrations activates NF-kappa B in primary human
      CD4+ T lymphocytes. Pb-induced activation of NF-kappa B is blocked by antibodies
      for p65 and p50 subunits but not cRel, indicating that the p65:p50 heterodimer
      (NF-kappa B) is involved. Functional activation of gene expression by Pb was
      confirmed using primary CD4+ T cells transfected with an NF-kappa B dependent
      reporter gene construct. Pb did not activate NF-kappa B in 4 different T cell
      lines, suggesting that lymphoid cell lines may not be reliable surrogates for the
      study of transcriptional activation in human T cells. These data suggest that NF
      kappa B may be an important molecular mediator of Pb-induced immunotoxicity.

PMID- 8878525
TI  - Genetic transfer of thermophilic trait from alkalophilic thermophilic Bacillus to
      E.coli.
AB  - The genomic library of alkalophilic thermophilic Bacillus was constructed in
      E.coli. A single recombinant [pATB 507 I] out of 10,000 colonies showed growth at
      50 degrees C, which produced large, opaque and mucilaginous colonies on LB. The
      IMViC biochemical tests suggested that the strain was E.coli, and scanning
      electron microscopy revealed increased cell length. The plasmid DNA from the
      thermophilic recombinant showed multiple bands. The cured strain showed
      ampicillin resistance (10 micrograms/ml) and presence of insert DNA in the
      genome, as revealed by southern blot analysis. The thermophilic trait was
      transformable with 10(-4) frequency of expression amongst the pATB 507I
      transformants. The hybridization of E.coli genomic DNA with labeled genomic DNA
      from alkalophilic thermophilic Bacillus suggested that the genetic
      recombination(s) of the insert DNA was an essential prerequisite for expression
      of thermophilic trait. The conjugative plasmid (RP4) mediated mobilization of
      thermophilic trait resulted in thermophilic conjugants after 2 h incubation.
      Southern blot analysis revealed that a single locus [5.6 kb Bam HI fragment] was
      involved in the transfer of thermophilic trait.

PMID- 8878526
TI  - The distal glutamic acid as an acid-base catalyst in the distal site of
      horseradish peroxidase.
AB  - The distal His is an essential amino acid residue as a general acid-base catalyst
      for peroxidase reaction cycle. However, the x-ray structure of chloroperoxidase
      revealed that Glu is located near the heme, suggesting that the carboxyl group
      also assists cleavage of O-O bond in peroxides. In this paper, we examined
      functional and structural properties of a horseradish peroxidase mutant having
      Glu instead of the distal His. Although this amino acid replacement depressed
      reaction rate with H2O2 and oxidation activity for guaiacol, the mutant still
      exhibited much higher activity than mutants in which the distal His was replaced
      by hydrophobic amino acid. Kinetic measurements suggest that the proton
      abstraction is decelerated in the mutant due to large fluctuation of the carboxyl
      group of the distal Glu. Therefore, we can conclude that Glu can be a potent acid
      base catalyst for peroxidase reaction cycle, if the carboxyl group can be fixed
      at the optimum position.

PMID- 8878527
TI  - Urokinase antisense oligodeoxynucleotides as a novel therapeutic agent for
      malignant glioma: in vitro and in vivo studies of uptake, effects and toxicity.
AB  - Antisense therapy might offer an improved treatment for patients with malignant
      glioma. We studied the uptake and effects of urokinase antisense
      oligodeoxynucleotides on rat and human glioma cells in vitro and the uptake and
      toxicity of these nucleotides in rat carcinomatosis and brain tumor models.
      Cultured glioma cells readily incorporated fluorescein isothiocyanate-conjugated
      oligonucleotides, as demonstrated by immunofluorescence microscopy and flow
      cytometry. Effects on urokinase expression as assessed by immunofluorescence
      microscopy varied according to cell line. Northern blot analysis showed decreases
      in urokinase expression with oligodeoxynucleotide treatment. Uptake into tumor
      cells was also demonstrated in vivo, with no detectable toxicity at
      concentrations exceeding expected therapeutic levels. These data are encouraging
      for the further study of antisense oligodeoxynucleotides as a new therapeutic
      modality for malignant glioma.

PMID- 8878528
TI  - Changes of expressions of phosphotyrosine phosphatases in rat hepatocellular
      carcinoma induced by 3'-methyl-4-dimethylamino-azobenzene.
AB  - Using rats with hepatocellular carcinoma induced by 3'-methyl-4-dimethylamino
      azobenzene (3'-MeDAB), we evaluated the expression of a protein tyrosine
      phosphatase (PTPase) in the tumor region, non-tumorous region and control rat
      liver. The expression of SHPTP2 increased 4.1 fold (p < 0.05) in mRNA, 2.1 fold
      (p < 0.01) in cytosol fraction, and 5.1 fold (p < 0.05) in membrane fraction,
      respectively, at a protein level in the tumor region compared with control liver.
      The expression of other phosphatases, LAR, LRP, and PTPase1B, did not change
      significantly. SHPTP2 phosphatase activity in the tumor region from rats also
      increased compared with control, suggesting that an increase of this activity may
      parallel the expression of SHPTP2. This increase of expression of SHPTP2 may
      contribute to the progression of hepatocellular carcinoma in this rat model.

PMID- 8878529
TI  - Purification and some properties of Clostridium sporogenes hemorrhagic toxin.
AB  - Clostridium sporogenes was isolated from rabbits with antibiotic-associated
      hemorrhagic diarrhea, then its hemorrhagic toxin was purified from the
      supernatant by means of hydrophobic interaction chromatography, hydroxyapatite
      chromatography, and gel filtration. The purified toxin's hemorrhagic activity was
      completely inhibited by EDTA, but not by PMSF or ovomucoid; and fully restored by
      the addition of such divalent cations as Zn2+, Ca2+ and Mg2+. The purified toxin
      did not hydrolyze azocasein, or type I or II collagens. But the purified toxin
      did hydrolyze type III and IV collagens, and also gelatins prepared from type I,
      II, III and IV collagens. It appears, therefore that C. sporogenes's toxin is a
      collagenase that hydrolyzes type III and IV collagens, which are major
      constituents of the tunica intima and media of blood vessels. And that fact
      suggests that hemorrhage caused by the toxin depend on its collagenase activity.

PMID- 8878530
TI  - Molecular imprinting: synthesis of polymer particles with antibody-like binding
      characteristics for glucose oxidase.
AB  - A phosphate buffer containing a mixture of glucose oxidase, acrylic acid
      derivatives, N,N'-1,2 dihydroxy-ethylene-bis(acrylamide), N,N'-(methylene)
      bisacrylamide and surface-modified silica was radically polymerized with
      (NH4)2S2O8. The polymer formed a thin layer around the silica beads. After
      sieving of these polymer particles, the surface bound protein was eluted. In
      rebinding assays and enzyme activity tests a specific binding capacity for
      glucose oxidase of up to 0.557 microgram GOD/100 mg dry weight of polymer
      particles could be determined. These polymer particles have the potential to be
      used as specific separation or detection material.

PMID- 8878531
TI  - Localization of Alzheimer-associated presenilin 1 in transfected COS-7 cells.
AB  - Presenilin 1 (PS 1) is the recently identified gene, located on chromosome 14, of
      which missense mutations can cause early-onset familial Alzheimer's disease. To
      understand the normal biological function of presenilin 1, we examined the sub
      cellular localization by using a monoclonal anti-presenilin 1 antibody. Immuno
      electronmicroscopic and biochemical analysis indicated that presenilin 1 is
      localized on cellular membrane (plasma, endoplasmic reticulum, and perinuclear)
      in COS-7 cells overexpressing presenilin 1. Interestingly, the PS 1
      immunoreactivity in the plasma membrane was concentrated in the regions with cell
      cell contact. This observation suggests a possible role of PS 1 on the cell
      membrane as a cell adhesion molecule.

PMID- 8878532
TI  - A new nonsteroidal chemical class of ligand for the ecdysteroid receptor 3, 5-di
      tert-butyl-4-hydroxy-N-isobutyl-benzamide shows apparent insect molting hormone
      activities at molecular and cellular levels.
AB  - Insect molting hormones, ecdysteroids, found in natural products so far have
      steroidal structures. However, nonsteroidal ecdysteroid agonists show promise as
      a new type of insecticide and may be useful as probes for the biochemical study
      of ecdysteroids. 3, 5-Di-tert-butyl-4-hydroxy-N-isobutyl-benzamide (DTBHIB),
      discovered by the combination of the automated ecdysteroid receptor binding assay
      and the ecdysteroid responsive gene expression assay, showed both ecdysteroid
      receptor binding activity and induction activities of ecdysteroid responsive
      genes. Furthermore, the inhibition of the Kc cell proliferation and the induction
      of the cell process protrusion were observed in the presence of DTBHIB in a dose
      response manner. A similar compound of DTBHIB, however, could neither bind the
      receptor nor induce the responsive gene. These results provide strong evidence
      for the ecdysteroid agonist activity of DTBHIB, which has a novel nonsteroidal
      chemical structure, and might be a valuable lead chemical for higher potential
      ecdysteroid agonists.

PMID- 8878533
TI  - Import into mitochondria of phospholipid hydroperoxide glutathione peroxidase
      requires a leader sequence.
AB  - An in vitro import system was used to characterize the mechanism of import of
      phospholipid hydroperoxide glutathione peroxidase (PHGPx) into mitochondria.
      Mitochondria were isolated from rat liver and incubated at 25 degrees C with
      [35S]methionine-labeled products of the in vitro translation of mRNA that encoded
      23-kDa and 20-kDa PHGPx. 23-kDa PHGPx was imported into mitochondria in a time
      dependent manner and was processed to yield the 20-kDa form of PHGPx. The 20-kDa
      form of PHGPx, without a leader sequence, associated weakly with mitochondria but
      was not imported. An analysis with an uncoupler of oxidative phosphorylation
      showed that a membrane potential in the mitochondria was also required for the
      import of PHGPx. It appears, therefore, that the leader sequence in the precursor
      to PHGPx is the signal for import into the mitochondria. This is the first report
      to indicate that the precursor to PHGPx is imported into the mitochondria via the
      action of a leader sequence.

PMID- 8878534
TI  - Molecular cloning and characterization of the human transmembrane protein
      tyrosine phosphatase homologue, phogrin, an autoantigen of type 1 diabetes.
AB  - A 4.7 kb cDNA of tyrosine phosphatase-like protein, phogrin, was isolated from a
      human islet cDNA library. Sequencing of the resulting clone identified a 3,045
      residue open-reading frame encoding a 1,015 amino acid polypeptide with predicted
      molecular mass of 111,303 daltons. Phogrin's amino acid sequence has a single
      transmembrane region and one putative tyrosine phosphatase catalytic domain.
      Phogrin is 74% identical to the ICA512/IA-2 autoantigen of type 1 diabetes in the
      cytoplasmic domain, but only 29% in the luminal domain. It showed > 90% identity
      to rat phogrin and mouse IA-2 beta. Autoantibody radioassays utilizing full
      length and the cytoplasmic domain of phogrin were compared. With positivity
      defined above the 99th percentile of 105 normal control subjects, 37 (48%) and 47
      (61%) of sera from 77 new-onset patients with type 1 diabetes were positive for
      autoantibodies to full-length and the cytoplasmic domain of phogrin,
      respectively. The assay utilizing cytoplasmic human phogrin gave higher
      sensitivity with identical specificity to the assay utilizing the full-length
      molecule primarily due to lower "background" binding. Phogrin is an additional
      major autoantigen for type 1 diabetes and the isolation of the cDNA of this
      molecule from human islets will aid in studies of the pathogenesis of type 1
      diabetes.

PMID- 8878535
TI  - Cationic lipids delay the transfer of plasmid DNA to lysosomes.
AB  - Plasmid 35S DNA, naked or associated with different cationic lipid preparations
      was injected to rats. Subcellular distribution of radioactivity in the liver one
      hour after injection, was established by centrifugation methods. Results show
      that at that time, 35S DNA has reached lysosomes. On the contrary, when 35S DNA
      was complexed with lipids, radioactivity remains located in organelles whose
      distribution after differential and isopycnic centrifugation, is clearly distinct
      from that of arylsulfatase, lysosome marker enzyme. Injection of Triton WR 1339,
      a specific density perturbant of lysosomes, four days before 35S DNA injection
      causes a density decrease of radioactivity bearing structures, apparent one hour
      after naked 35S DNA injection but visible only after more than five hours, when
      35S DNA associated with a cationic lipid is injected. These observations show
      that cationic lipids delay the transfer to lysosomes, of plasmid DNA taken up by
      the liver.

PMID- 8878536
TI  - Heparin functions as a hepatotrophic factor by inducing production of hepatocyte
      growth factor.
AB  - Hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, is a
      hepatotrophic factor for liver regeneration. Addition of heparin to cultures of
      human fibroblasts, leukemic cells, and umbilical vein endothelial cells
      stimulated HGF production to 3-6-fold higher levels than seen in the absence of
      heparin. Administration of heparin to rats increased blood HGF levels to a 2.5-5
      fold higher level than that in control rats given saline alone, and consequently
      induced a remarkable enhancement of liver regeneration in vivo after a 30%
      partial hepatectomy. However, heparin had no stimulatory effect on DNA synthesis
      of hepatocytes in primary culture. These results indicate that heparin has
      hepatotrophic function, an action possibly mediated through the stimulation of
      production of HGF.

PMID- 8878537
TI  - Translational control during recovery from heat shock in the absence of heat
      shock proteins.
AB  - Heat shock results in a reduction in translational efficiency and an increase in
      mRNA stability in plants that is proportional to the severity of the stress. To
      determine whether the absence of heat shock proteins may affect the observed
      changes during translation or mRNA turnover, the effect that inhibiting
      transcription during a heat shock has on the subsequent translation of a reporter
      mRNA was examined. The presence of actinomycin D repressed heat shock protein
      synthesis in response to the application of a heat shock by more than 80%. The
      translational efficiency of the reporter mRNA was subject to a greater degree of
      repression following a heat shock when transcription was inhibited than it was in
      heat-shocked cells in which transcription was not inhibited. In contrast,
      inhibiting transcription during a heat shock did not prevent the heat-mediated
      increase in mRNA stability. These data suggest that ongoing transcription is
      needed during a heat shock to support a basal level of translational activity in
      the subsequent recovery from the stress but does not appear to be required for
      the heat-mediated increase in mRNA stability.

PMID- 8878538
TI  - Activation of Na+/H+ exchanger is not involved in the PDGF-BB-induced DNA
      synthesis in vascular smooth muscle cells.
AB  - HOE 694 [(3-methylsulphonyl-4-piperidinobenzoyl)guanidine methanesulphonate] was
      characterized as a new, potent, non-amiloride inhibitor of the Na+/H+ exchanger.
      In order to elucidate whether the Na+/H+ exchanger isoform 1 (NHE-1) is involved
      in the PDGF-BB-induced DNA-synthesis in vascular smooth muscle cells, we
      investigated the effect of HOE 694 and EIPA on the PDGF-BB-induced DNA synthesis.
      EIPA (10 microM) inhibited the PDGF-BB-induced stimulation of the Na+/H+
      exchanger and the PDGF-BB-induced DNA synthesis in a concentration-dependent
      manner. HOE 694 (1-50 microM) dose-dependently inhibited the PDGF-BB-induced
      stimulation of the Na+/H+ exchanger but had no significant effects on DNA
      synthesis. Our findings suggest that activation of the Na+/H+ exchanger is not
      essential for PDGF-BB-induced vascular smooth muscle cell growth.

PMID- 8878539
TI  - Cyclic GMP elevation by 5-hydroxytryptamine is due to nitric oxide derived from
      endogenous nitrosothiol in NG108-15 cells.
AB  - To clarify the involvement of nitric oxide (NO) derived from nitrosothiols (RSNO)
      in 5-hydroxytryptamine (5-HT)-induced Ca(2+)-independent cGMP formation (CIGF) in
      NG108-15 cells, we investigated the effects of 5-HT on intracellular contents of
      RSNO as well as of NO metabolites. 5-HT stimulation resulted in an increase in
      the intracellular contents of nitrate and cGMP. RSNO was detected in NG108-15
      cells and was decreased by 5-HT stimulation. Furthermore, the time course of
      nitrate increase was coincident with that of RSNO decrease. CarboxyPTIO inhibited
      5-HT-induced CIGF, whereas oxyhemoglobin failed to inhibit it. The data suggest
      that NO is stored in a stable form as RSNO and that 5-HT stimulates NO generation
      from endogenous RSNO, which is followed by elevation of cGMP via activation of
      cytosolic guanylyl cyclase by NO in NG108-15 cells. We suggest the existence of a
      novel 5-HT signal transduction pathway involved in NO generation in NG108-15
      cells.

PMID- 8878540
TI  - Structural differences in the ability of lysophospholipids to inhibit endothelium
      dependent hyperpolarization by acetylcholine in rat mesenteric arteries.
AB  - The effects of different lysophospholipids on endothelium-dependent
      hyperpolarization by acetylcholine were examined in rat mesenteric arteries.
      Lysophosphatidylcholine with 14 or longer carbon acyl chain significantly
      inhibited the hyperpolarization, while that with 12 or lesser carbon acyl chain
      was without effect. Lysophosphatidylcholine with unsaturated acyl chain also
      showed a potent inhibition. Lysophosphatidylinositol and lyso-platelet activating
      factor, but not phosphatidylcholine, lysophosphatidic acid,
      lysophosphatidylethanolamine or lysophosphatidylserine, suppressed the
      hyperpolarization. These results suggest that the length of the carbon acyl chain
      and the size of the polar head group may be crucial for the effects of
      lysophospholipids on endothelium-dependent hyperpolarization. Accumulation of
      these lysophospholipids may play an important role in endothelial dysfunction
      associated with atherosclerosis.

PMID- 8878541
TI  - An unusual bacterial reverse transcriptase having LVDD in the YXDD box from
      Escherichia coli.
AB  - A minor population of wild strains of Escherichia coli contains a gene for
      reverse transcriptase (RT) which is responsible for the synthesis of multicopy
      single-stranded DNA (msDNA), a branched DNA-RNA complex. A DNA fragment capable
      of synthesizing msDNA was cloned from strain ECOR-58, one of the 72 wild strains
      in the ECOR collection. The complete open reading frame of a novel reverse
      transcriptase, designated ECOR-58 RT, was identified. ECOR-58 RT consisted of 408
      amino acid residues, and its 227-residue polymerase domain from residue 43 to 269
      showed significant homologies to all the other bacterial RTs so far identified.
      Most significantly, its YXDD box, the most highly conserved sequence in all RTs
      from prokaryotes to eukaryotes, was found to be replaced with LVDD. ECOR-58 RT
      was found to be most distantly related in a phylogenetic tree to all 9 other
      bacterial RTs so far identified.

PMID- 8878542
TI  - Some ideas on the origin of otoacoustic emissions.
AB  - The presence of a basal activity in the cochlea is postulated. This activity is
      generated by the OHCs which are made to vibrate at their intrinsic resonant
      frequency by Brown's motion. In keeping with the chaos theory clusters vibrating
      in phase at one and the same frequency aggregate in the process. These clusters
      alternate with one another. Minor pathology enhances OHC synchronization so that
      the clusters become larger. As a result, more energy is projected back into the
      outer ear canal. This energy is high enough for being picked up as SOAE by
      current measuring tools.

PMID- 8878543
TI  - Molecular cloning, functional expression, and selective regulation of ovine
      prostaglandin H synthase-2.
AB  - Structural characterization for ovine prostaglandin H synthase-1 (PGHS-1) is
      extensive, but the corresponding structure for the homologous ovine PGHS-2
      isoform is undefined. Accordingly, we isolated a full-length (3.4 kb) ovine PGHS
      2 cDNA from a primary-culture cell model (ovine tracheal epithelial cells)
      originally described as containing both PGHS isoforms. Analysis of ovine PGHS-2
      cDNA sequence indicated conservation of critical amino acid residues, but
      differences in other hydrophilic regions allowed for the development of an anti
      peptide antibody highly selective for PGHS-2. Enzymatic activities of the
      recombinant ovine PGHS isozymes indicated significant differences in response to
      aspirin-acetylation consistent with the characteristics of endogenous cellular
      PGHS activities under basal and serum-induced conditions. The results fully
      account for previous evidence of two distinct PGHS activities in cultured airway
      epithelial cells and provide for additional definition of PGHS structure-function
      relationships.

PMID- 8878544
TI  - Rapamycin-sensitive phosphorylation of ribosomal protein S17 by p70 S6 kinase.
AB  - The immunosuppressant rapamycin selectively inhibits the phosphorylation of the
      ribosomal protein S6. We demonstrate that rapamycin also inhibits the
      phosphorylation of another ribosomal protein identified by isolation and
      microsequencing as ribosomal protein S17. The phosphorylation of S17 in T- and B
      cell lines is specifically inhibited by rapamycin. IL-3 induces the
      phosphorylation of S17 in the IL3-responsive cell line, BaF3, and this
      phosphorylation is inhibited by rapamycin. Purified preparations of recombinant
      S17 are phosphorylated in vitro by immunoprecipitated p70 S6 kinase. Finally,
      recombinant S17 is phosphorylated by cellular fractions containing p70 S6 kinase,
      whereas no other cellular fractions were found to contain any significant S17
      kinase activity. These data suggest that the ribosomal protein S17 is a substrate
      for p70 S6 kinase both in vitro and in vivo and that S17 may be involved in
      mediating the inhibitory effects of rapamycin on protein translation in cells of
      different lineages.

PMID- 8878545
TI  - A role of peroxides in Ca2+ ionophore-induced apoptosis in cultured rat cortical
      neurons.
AB  - The implication of reactive oxygen species for the Ca2+ ionophore ionomycin
      induced apoptosis was investigated in cultured cortical neurons from embryonic
      rats. Ionomycin increased the production of intracellular peroxides as measured
      by flow cytometric analysis with 6-carboxy-2'7'-dichorodihydrofluorescein
      diacetate, di(acetoxymethyl ester). Low doses of ionomycin increased the level of
      manganese-superoxide dismutase (Mn-SOD). In addition, N-acetyl-L-cysteine
      prevented apoptotic neuronal death induced by ionomycin in a dose-dependent
      manner. Buthionine sulfoximine suppressed the effect of N-acetyl-L-cysteine.
      These results suggest that peroxides and redox-regulation play an important role
      in the apoptosis of neurons induced by elevation of intracellular Ca2+
      concentration.

PMID- 8878546
TI  - Passive response of Saccharomyces cerevisiae to osmotic shifts: cell volume
      variations depending on the physiological state.
AB  - The passive osmoregulation phase of S. cerevisiae has been characterized for
      different physiological states. The relative cell volume decrease of exponential
      cells was found to be greater than the volume decrease of stationary ones during
      the hyperosmotic shock. The application of a slow and linear increase in osmotic
      pressure has allowed the distinguishing of two phases in the passive
      osmoregulatory response of cells and to calculate the turgor pressure of S.
      cerevisiae. Cells in the exponential phase have a weak turgor pressure (0.05 MPa)
      compared to the turgor pressure of stationary phase cells (0.2 MPa).
      Nevertheless, the turgor pressure and the relative decrease in volume were found
      to be independent of the size of cells for the same physiological state.

PMID- 8878547
TI  - Distinct composition of viral quasispecies between ascites and serum samples from
      patients with late stage chronic hepatitis C.
AB  - By performing single-strand conformation polymorphism and PCR-cloning followed by
      sequencing, the amino acid composition of hepatitis C virus hypervariable and
      variable regions were analyzed in ascites and serum samples from two patients
      with late stage chronic hepatitis C. In patient-LC, the major ascitic clone was
      constituted by a minor serum-derived clone, while the major serum derived clone
      was absent in the ascites. In patient-HCC, the major ascitic clone was defective
      and genetically different from all the serum-derived clones. In addition, anti
      genomic HCV RNA was detected in the ascitic mononuclear cells from patient-LC.
      These results argued that the peritoneal cavity served as a relatively isolated
      environment for evolution of distinct composition of viral quasispecies.

PMID- 8878548
TI  - Multiple forms of tRNA(Lys3) in HIV-1.
AB  - tRNALys3 is the primer for HIV-1 reverse transcriptase (RI) and is selectively
      incorporated into HIV-1 during viral assembly. While whole cell extracts of
      uninfected or infected cells contain only one detectable form of tRNALys3,
      multiple forms of tRNALys3 are detected in the virus released into the cell
      culture media. These tRNALys3 isoacceptors are found in HIV-1 produced from newly
      infected cord blood lymphocytes and from cells chronically infected with HIV-1,
      such as the lymphocytic cell line H9 and the monocytic cell lines U937 and PLB.
      They can be detected through the use of either RPC-5 column chromatography of
      tRNA aminoacylated with radioactive lysine or northern blot analysis using a
      tRNALys3-specific DNA hybridization probe. Both RPC-5 chromatography and northern
      blot analysis show the cytoplasmic form of tRNALys3 to be the major abundance
      form of tRNALys3 in the virus. Starting with the viral RNA isolated from HIV
      (PLB), the tRNALys3 species resolved by RPC-5 into peaks 2, 3, and 4 were
      deacylated and 3' end-labeled by heat-annealing the RNA in each peak to synthetic
      HIV genomic RNA, and extending the hybridized species one base using HIV-1 RT and
      radioactive dCTP. An electrophoretic comparison of the partial T1 digest pattern
      of purified human placental tRNALys3 with those of the RPC-5 resolved species
      showed that the labeled RNA species in each peak was tRNALys3. These radioactive
      tRNALys3 species retained their relative mobilities when rechromatographed on RPC
      5. When total HIV (PLB) RNA was used as the source of primer/template, and
      similarly extended with RT in the presence of radioactive dCTP, the major priming
      tRNA resolved by RPC-5 had a chromatographic mobility identical to peak 3. This
      tRNA primer has a T1 digest pattern identifying it as tRNALys3. These results
      indicate that the major tRNALys3 species present in the virus is also the major
      tRNALys3 isoacceptor used as the primer for reverse transcription.

PMID- 8878549
TI  - Immunological detection of CYP2E1 in fresh rat lymphocytes and its
      pretranslational induction by fasting.
AB  - The level of ethanol-inducible cytochrome P450 2E1 (CYP2E1) in fresh lymphocytes
      compared with cultured cells and its induction mechanism by fasting were studied.
      CYP2E1 in the homogenate and S-9 fraction of fresh lymphocytes was elevated about
      5-fold by fasting, comparable to the induction observed in cultured lymphocytes.
      This induction was accompanied by increased level of CYP2E1 mRNA, confirmed by
      nested RT-PCRs, Southern blot, and DNA sequence analysis. Our data thus
      demonstrated that CYP2E1 in fresh lymphocytes is pretranslationally induced by
      fasting, in parallel to the hepatic enzyme, and that measurement of CYP2E1 in the
      lymphocyte homogenate can be useful to estimate the hepatic CYP2E1 level in a
      relatively noninvasive manner.

PMID- 8878550
TI  - Regulation of acetyl coenzyme-A carboxylase gene in a transgenic animal model.
AB  - The gene for acetyl-CoA carboxylase, the rate-limiting enzyme in the biosynthesis
      of long-chain fatty acids, contains two promoters; promoter I (PI) and promoter
      II (PII) which are responsible for generation of class I and class II ACC mRNAs,
      respectively. Class I ACC mRNAs are present in adipose tissue, but only a trace
      was found in the liver under normal physiological conditions. However, class I
      mRNAs were induced under stimulated lipogenic conditions. To investigate how PI
      is regulated in vivo, we generated transgenic mice containing a reporter gene
      under the control of PI. In transgenic mice, PI is generally inactive and a small
      amount of PI activity was found only in the adipose tissues of female animals.
      Stimulated lipogenic conditions activated PI about 17-fold over normal conditions
      and again only in white adipose tissues of female animals.

PMID- 8878551
TI  - Mutations of E2F-4 trinucleotide repeats in colorectal cancer with microsatellite
      instability.
AB  - Genetic instability at microsatellites in some colorectal cancer (CRC) have been
      linked to the defects of human mismatch repair genes, but the targets of these
      defective genes have been largely unknown. We screened CRC specimens for
      alteration of E2F-4 gene by analyzing both cDNA and genomic sequences along with
      replication error (RER+) phenotype. Two out of 20 sporadic CRC patients showed
      RER+ phenotype. We found tumor-specific copy number alteration in 13 consecutive
      trinucleotide (CAG) repeats within the coding exon of E2F-4 exclusively in these
      2 specimens. Thus, E2F-4 may be a clue of the target gene of defective repair
      genes in CRC with genetic instability in addition to the TGF-beta type II
      receptor gene.

PMID- 8878552
TI  - Elevated expression of DNA polymerase beta gene in glioma cell lines with
      acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)
      3- nitrosourea.
AB  - We investigated the expression of DNA polymerase beta (beta-pol) and O6
      methylguanine-DNA methyltransferase (MGMT) in human glioma cells with acquired
      resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3
      nitrosoure a (ACNU) and in the parent cells. ACNU-resistant T430 (T430R) and A172
      (A172R) glioma cell lines were established following repeated exposure to ACNU.
      The level of MGMT mRNA expression was elevated in T430R, but not in A172R. In
      contrast, the level of beta-pol mRNA expression and the level of beta-pol protein
      were elevated in A172R, compared with the parent cells. While the mechanism of
      MGMT repair has been considered to be important in the drug resistance of human
      brain tumors to ACNU, our present results demonstrate that beta-pol may also play
      an important role in the acquisition of tumor cell resistance to ACNU in human
      gliomas.

PMID- 8878553
TI  - Proteasome-dependent regulation of p21WAF1/CIP1 expression.
AB  - Proteasome-dependent degradation of regulatory proteins is a known mechanism of
      cell cycle control. We found that the proteasome-specific inhibitor lactacystin
      (LC) induced expression of the cell cycle inhibitor p21WAF1/CIP1 in human cancer
      cells regardless of their p53 status. Both wild-type (wt) p53 and p21 protein
      levels increased by two hours in wt p53 containing cells, whereas mutant (mt) p53
      levels decreased and the increase in p21 levels was delayed to 6 hr following
      inhibition of proteolysis by LC in mt p53 expressing cells. We found that wt but
      not mt p53 expressing cells increased p21 mRNA and p21-promoter reporter levels
      following LC exposure, suggesting transcriptional induction of p21. Inhibition of
      protein synthesis by cycloheximide demonstrated increased p21 protein half-life
      in the presence of LC in mutant p53 containing cells. p21 induction was
      correlated with the cytostatic effects of LC. The results suggest that p21
      protein expression could be increased by transcriptional mechanisms as well as
      inhibition of proteolysis by LC.

PMID- 8878554
TI  - An in vitro system for identifying agents capable of changing serum
      lipoprotein(a) concentration by regulating the transcriptional activity of the
      apolipoprotein(a) gene promoter.
AB  - A high serum concentration of lipoprotein(a) [Lp(a)] is a significant and
      independent risk factor for cardiovascular disease. We examined the effects of
      agents on the transcriptional activity of the apolipoprotein(a) [apo(a)] gene
      promoter and determined whether drugs identified by this assay would affect the
      serum concentration of Lp(a) in vivo. All-trans-retinoic acid (ATRA) and
      interleukin-6 increased the transcriptional activity of the apo(a) gene promoter
      2.1- and 2.5-fold, respectively, whereas danazol reduced activity to 76% of the
      control value. Triiodothyronine had no effect on transcriptional activity.
      Treatment of two acute promyelocytic leukemia patients with ATRA induced maximal
      2.7- and 3.2-fold increases in serum Lp(a) concentrations, respectively. Thus,
      the in vitro luciferase assay system is capable of identifying agents that affect
      the serum concentration of Lp(a) and thus may prove beneficial in the screening
      of new drugs for treatment of individuals with high serum Lp(a) concentrations.

PMID- 8878555
TI  - Contribution of regions 3' and 5' to the hIL-5 gene on the expression of rhIL-5
      in CHO-cells.
AB  - The effect of the presence of the regions 5' and 3' of the hIL-5 gene on the
      expression of recombinant hIL-5 in CHO-cells was investigated. The 3.2 kb hIL-5
      gene-fragment was cloned and four different dexamethasone-inducible rhIL-5
      mammalian expression-vectors were constructed, each containing a different part
      of the gene-fragment. Results indicated that deletion of the region 5' to the
      gene increases production three-fold whereas a four-fold decrease in production
      was observed with deletion of the region 3' to the gene. Deletion of both regions
      increased rhIL-5 production by only one and a half-fold. These results indicate
      that there are elements in a 928 bp region 3' to the gene, including the 3'-NTR,
      that have an enhancing or stabilizing effect on expression of hIL-5 in CHO-cells.

PMID- 8878556
TI  - Substitution of two variant residues in the protein tyrosine phosphatase-like
      PTP35/IA-2 sequence reconstitutes catalytic activity.
AB  - The PTP35/IA-2 protein shows high homology to protein tyrosine phosphatases
      (PTPases) but harbours a few changes in invariant PTPase residues. Accordingly,
      PTP35/IA-2 has been reported to lack catalytic activity in vitro, and its in vivo
      biological function remains to be determined. We investigated if reversion of
      selected amino acids to the PTPase consensus could reconstitute enzymatic
      activity. Substitution of aspartic acid 911 in the putative active site with
      alanine resulted in the appearance of low but reproducible activity on pNPP
      dephosphorylation. Moreover, contemporary replacement of alanine 877 with
      aspartic acid greatly increased the catalytic efficiency of the D911A mutant. The
      A877D/D911A double mutant protein was also found to specifically dephosphorylate
      myelin basic protein phosphorylated on tyrosine. These results suggest that the
      general scaffold of the PTP35 protein is compatible with a common catalytic
      mechanism shared by PTPases and argue against an intrinsic enzymatic function of
      the wild type form.

PMID- 8878557
TI  - 4-hydroxynonenal specifically inhibits c-myb but does not affect c-fos
      expressions in HL-60 cells.
AB  - 4-Hydroxynonenal, an aldehyde produced from lipid peroxidation of cellular
      membranes, inhibits growth and induces differentiation of HL-60 human leukemic
      cell line. Since it is highly unstable in the culture medium, its effectiveness
      is increased when added repeatedly to the cell suspension. We have previously
      demonstrated that HNE inhibits c-myc but not N-ras expression in HL-60 cells.
      Here we investigate its effect on the expression of c-myb and c-fos, two early
      genes involved in the induction of myeloid and monocytic differentiation.
      Moreover, since c-fos is directly correlated with the intracellular level of
      cAMP, we also analysed the cAMP concentration after aldehyde treatment. HNE
      significantly inhibits c-myb expression during and after repeated treatments. A
      single administration of 1 microM HNE decreases c-myb mRNA at 1 hour whereas 10
      microM HNE inhibits c-myb expression from 3 to 6 hours after treatment, and then
      the expression returns to the control level. By contrast, c-fos expression and
      intracellular cAMP concentration do not show any significant change after HNE
      treatments.

PMID- 8878558
TI  - Characterization of the human and mouse cDNAs coding for S100A13, a new member of
      the S100 protein family.
AB  - Here we report the characterization of the human S100A13 cDNA coding for a novel
      calcium-binding protein belonging to the S100 protein family. The predicted
      S100A13 protein shows sequence homologies to other S100 proteins between 50.5%
      (to S100A5) and 59.3% (to S100A12). High mRNA amounts were found in skeletal
      muscle, heart, kidney, ovary, small intestine and pancreas. Since twelve S100
      genes are clustered on human chromosome 1q21, we determined the chromosomal
      localization of the human S100A13. It co-localizes with S100A1 on the cluster.
      Furthermore, we characterized the cDNA sequence coding for the mouse homolog of
      S100A13. Similar to the putative human protein, mouse S100A13 is composed of 98
      amino acids displaying a homology of 86.7% compared to human S100A13.

PMID- 8878559
TI  - Insulin internalization in the absence of the insulin receptor tyrosine kinase
      domain is insufficient for mediating intracellular biological effects.
AB  - The intracellular portion of the human insulin receptor (hIR) beta-subunit
      contains distinct functional domains including the exon 16-encoded juxtamembrane
      (JM) domain that mediates endocytosis, and the tyrosine kinase (TK) domain that
      mediates insulin's metabolic and mitogenic actions. To explore the functional
      relationship between these domains and to determine the role of insulin
      internalization in insulin action, we constructed and studied the endocytic and
      signaling properties of an hIR mutant truncated at Glu-1012. This truncation
      removes the carboxyl-terminal 343 amino acids containing essentially all of the
      TK domain but leaves behind the exon 16-encoded JM domain that is necessary for
      endocytosis, plus an additional 35 amino acids downstream. The wild-type (hIR-WT)
      and mutant (hIR delta 343) receptors were stably expressed in CHO cells and their
      abilities to mediate various insulin-stimulated functions were comparatively
      analyzed. In cells expressing hIR-WT, insulin markedly enhanced tyrosine
      phosphorylation of the beta-subunit and of the endogenous 185 kDa substrate
      whereas these effects were completely absent in cells expressing hIR delta 343.
      The hIR delta 343 receptors retained the ability to internalize a significant
      amount of surface-bound insulin at 37 degrees C. However, they were unable to
      mediate either the short or long-term biological effects of insulin as determined
      by assaying insulin-stimulated glucose uptake (assessed by 2-deoxyglucose
      uptake), protooncogene expression (measured by Northern blot analysis of c-fos
      mRNA) and DNA synthesis (measured by 3H-thymidine incorporation). These results
      indicate that the hIR beta-subunit JM and TK domains can be functionally
      uncoupled, and that insulin internalization in the absence of hIR TK domain and
      kinase activity is insufficient for mediating intracellular insulin action.

PMID- 8878560
TI  - Molecular cloning of the novel human G protein-coupled receptor (GPCR) gene
      mapped on chromosome 9.
AB  - A novel human GPCR gene was cloned by PCR with degenerate primers designed from
      cannabinoid type 1 receptor (CB1) sequences and a full-length clone was isolated
      by screening of a human genomic DNA library. This gene, termed EDG-3, is highly
      homologous (51.9 % overall and 69.2 % in seven transmembrane regions) to human
      EDG-1, 47.9 % to rat AGR16 but only 28.0 % to human CB1 receptor. The Northern
      hybridization analysis showed that a 2.8 kb transcript of EDG-3 is abundantly
      expressed in the heart followed by placenta, kidney and liver. The EDG-3 gene was
      mapped on the human chromosome 9q22.1-q22.2 by fluorescence in situ hybridization
      analysis. Although the ligand and physiological role of this receptor is unknown,
      this gene may be a new member of the EDG family.

PMID- 8878561
TI  - Structural characterization of the metal binding site in the cysteine-rich region
      of HIV-1 Tat protein.
AB  - Human immunodeficiency virus type-1 Tat protein transactivates the gene
      expression of retrovirus. The unique cysteine-rich region of Tat protein is
      biologically essential. This study characterizes the structural features of a
      synthetic Tat21-38 peptide covering the cysteine-rich region with Zn binding
      property. UV titrations confirm Tat peptide binds with two Zn2+ cations maximally
      per monomer, as previously reported(1). Only monomer is observed from the
      electrospray mass spectrum. Interestingly, a modified Ellman reaction (2) can
      differentiate a metal chelated thiolate of cysteine residue from a free one.
      Three disulfide bonds are formed in apo-Tat21-38 peptide. One Tat21-38 molecule
      utilize four Cys residues in coordination with the first incorporated Zn2+
      cation. Five out of seven Cys residues are coordinating with two Zn cations of
      the complex Zn-Tat21-38 (2:1). A model of the coordination arrangement of Zn
      binding sites at different states is proposed.

PMID- 8878562
TI  - Activation of mitogen-activated protein kinase by the carcinogenic mycotoxin
      fumonisin B1.
AB  - Recent studies indicate that the mycotoxin and putative carcinogen fumonisin B1
      stimulates mitogenesis in Swiss 3T3 fibroblasts. Because mitogen-activated
      protein kinase (MAPK) is a key enzyme in the signal transduction pathways
      activated by many mitogens, we hypothesized that fumonisin B1 might modulate MAPK
      activity. Consistent with other reports, we observed that fumonisin B1 is
      synergistic with insulin for mitogenesis in Swiss 3T3 cells. We also observed
      that: (1) fumonisin B1 stimulates rapid, transient activation of MAPK; and (2)
      the dose-response curve for fumonisin B1-stimulated activation of MAPK is similar
      to the dose-response curve for the mitogenic effects of fumonisin B1. In contrast
      to fumonisin B1, insulin stimulates minimal activation of MAPK in Swiss 3T3
      cells. The observation that fumonisin B1 and insulin differ with respect to the
      modulation of MAPK activity suggests a possible mechanism for their synergistic
      stimulation of mitogenesis in Swiss 3T3 cells.

PMID- 8878563
TI  - Therapeutic angiogenesis following arterial gene transfer of vascular endothelial
      growth factor in a rabbit model of hindlimb ischemia.
AB  - The plasmid phVEGF165, expressing the 165-amino-acid isoform of vascular
      endothelial growth factor (VEGF), an endothelial cell specific mitogen, was
      applied to the polymer coating of an angioplasty balloon and delivered
      percutaneously to the iliac artery of rabbits in which the femoral artery had
      been excised to cause hindlimb ischemia. Site-specific transfection of phVEGF165
      resulted in augmented development of collateral vessels documented by serial
      angiograms, and increased capillary density as well as increased
      capillary/myocyte ratio documented histochemically at necropsy. Consequent
      amelioration of the hemodynamic deficit in the ischemic limb was documented by
      improvement in the calf blood pressure ratio (ischemic/normal limb) to 0.70 +/-
      0.08 in the VEGF-transfected group vs 0.50 +/- 0.18 in controls (p < 0.05). These
      findings suggest that site-specific arterial gene transfer of VEGF165 may achieve
      physiologically meaningful therapeutic modulation of vascular insufficiency.

PMID- 8878564
TI  - A human kidney cDNA which induces a cell surface protein epitope recognized by a
      monoclonal antibody against galactosylceramide.
AB  - Antibodies against the myelin glycolipid galactosylceramide are widely used to
      study the distribution and function of this molecule. However, anti
      galactosylceramide antibodies are not monospecific and have been shown to
      recognize epitopes carried not only by other glycolipids, but also by proteins.
      Using expression cloning we have identified a human kidney cDNA which induces a
      cell-surface protein recognized by the anti-galactosylceramide monoclonal
      antibody R-mab. These findings further support the idea that cross-reactive
      proteins may mediate some of the biological effects of the anti
      galactosylceramide antibodies.

PMID- 8878565
TI  - Antipneumococcal activities of cefpirome and cefotaxime, alone and in combination
      with vancomycin and teicoplanin, determined by checkerboard and time-kill
      methods.
AB  - The checkerboard titration method was used to test the synergy of cefpirome and
      cefotaxime with teicoplanin or vancomycin against 35 penicillin-susceptible, 34
      penicillin-intermediate, and 31 penicillin-resistant pneumococci. The MICs at
      which 50 and 90% of isolates are inhibited (MIC50s and MIC90s, respectively) of
      both cefpirome and cefotaxime were 0.016 and 0.06 microgram/ml, respectively, for
      penicillin-susceptible strains and 0.125 and 0.5 microgram/ml, respectively, for
      penicillin-intermediate strains. The MIC50s and MIC90s of cefotaxime for
      penicillin-resistant strains were 1.0 and 2.0 micrograms/ml, respectively, and
      those of cefpirome were 0.5 and 1.0 microgram/ml, respectively. All pneumococci
      were inhibited by cefpirome at MICs of < or = 1.0 microgram/ml. The MIC50s and
      MIC90s of vancomycin and teicoplanin (0.25 and 0.25 microgram/ml and 0.03 and
      0.03 microgram/ml, respectively) did not differ for the three groups.
      Checkerboard synergy studies showed that cefpirome and vancomycin showed synergy
      for 31 strains (fractional inhibitory concentration [FIC] indices, < or = 0.5)
      cefpirome and teicoplanin showed synergy for 18 strains, cefotaxime and
      vancomycin showed synergy for 51 strains, and cefotaxime and teicoplanin showed
      synergy for 27 strains. Cefpirome and vancomycin had FIC indices indicating
      indifference (2.0) for two strains, and cefotaxime and vancomycin had FIC indices
      indicating indifference for one strain. All other FIC indices indicating
      indifference or additivity were > 0.5 to 1.0. No FIC indices indicating
      antagonism (> 4.0) were found. Synergy between beta-lactams and glycopeptides for
      three susceptible, three intermediate, and three resistant strains were tested by
      the time-kill assay, and all combinations were synergistic by this method.
      Synergy between cephalosporins and glycopeptides can be demonstrated and may be
      useful for the treatment of pneumococcal infections, especially meningitis.

PMID- 8878566
TI  - Efficacy of single-dose ceftriaxone in experimental otitis media induced by
      penicillin- and cephalosporin-resistant Streptococcus pneumoniae.
AB  - We used a gerbil model of otitis media to assess the efficacy of single-dose
      ceftriaxone against three Streptococcus pneumoniae strains highly resistant to
      penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to
      ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced
      by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic
      treatment was administered subcutaneously at 2 h postinfection. Infection status
      was checked 2 days later by counting the bacteria in middle ear and cerebrospinal
      fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we
      tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment
      outcome was equivalent to that with amoxicillin, which was used as a reference
      (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear
      samples, and the rate of cerebrospinal fluid culture positivity was significantly
      reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was
      obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains.
      Pharmacokinetic study indicates that the values of the parameters in plasma after
      the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33
      micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve,
      488 micrograms.h.ml-1) were still suboptimal compared with the values of the
      parameters measured in pediatric patients after intravenous or intramuscular
      administration of a dose of 50 mg/kg. Our results indicate the efficacy of
      ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and
      provide a basis for the clinical use of single-dose ceftriaxone against
      pneumococcal otitis media.

PMID- 8878567
TI  - Mutants of feline immunodeficiency virus resistant to 2',3'-dideoxy-2',3'
      didehydrothymidine.
AB  - We selected mutants of feline immunodeficiency virus (FIV) that are resistant to
      2',3'-dideoxy-2',3'-didehydrothymidine (d4T). Two mutants were selected in
      cultured cells with a stepwise increase in d4T concentration, resulting in
      mutants able to replicate in 100 microM d4T. These mutants were three- to sixfold
      more resistant to d4T than wild-type FIV. They were also cross-resistant to 3'
      azido-3'-deoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine, 2',3'
      dideoxycytidine, 2',3'-dideoxyinosine, and 9-(2-phosphonylmethoxyethyl)adenine,
      and they were highly resistant to phosphonoformic acid (PFA). Plaque-purified
      mutants were isolated from each of the mutant populations. The mutant phenotype
      was stable, because both of the plaque-purified mutants remained d4T resistant
      even after three passages in the absence of d4T. One of the plaque-purified
      mutants, designated D4R-3c, was further characterized. Compared with wild-type
      reverse transcriptase (RT), RT purified from D4R-3c was 3-fold resistant to
      inhibition by the 5'-triphosphate of d4T, 10-fold resistant to inhibition by the
      5'-triphosphate of AZT, and 6-fold resistant to PFA. D4R-3c had a single point
      mutation in the RT-encoding region of the pol gene at position 2474, resulting in
      a Val to Ile mutation at codon 47 of the FIV RT. The role of this mutation in d4T
      resistance was confirmed by site-directed mutagenesis.

PMID- 8878568
TI  - Molecular aspects of high-level resistance to sulbactam-cefoperazone in
      Klebsiella oxytoca clinical isolates.
AB  - Nine Klebsiella oxytoca strains which demonstrated resistance to the combination
      of sulbactam and cefoperazone were isolated from geographically separate
      hospitals in Japan in 1995. Among them, K. oxytoca SB23 showed high-level
      resistance to sulbactam-cefoperazone (MIC > 128 micrograms/ml) and aztreonam
      (MIC, 128 micrograms/ml). The sulbactam-cefoperazone resistance was not
      transferred from strain SB23 to Escherichia coli CSH2 by conjugation, beta
      Lactamase RbiA, produced by strain SB23, was purified, and the molecular mass was
      estimated to be 29 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Kinetic parameters for RbiA revealed that cefoperazone and
      aztreonam were hydrolyzed efficiently by this enzyme. Moreover, ceftazidime and
      imipenem were also hydrolyzed weakly by RbiA, although strain SB23 did not show
      any resistance to these agents. Clavulanate, sulbactam, and tazobactam failed to
      block the hydrolysis of cefoperazone by RbiA. The structural gene of RbiA
      (blaRBI) was cloned and sequenced, and the deduced amino acid sequence of RbiA
      demonstrated high-level similarities to those of the beta-lactamases found in K.
      oxytoca D488, E23004, and plasmid-mediated MEN-1, which have been classified into
      Bush functional group 2be. Although RbiA demonstrates high-level molecular
      similarity to the enzymes in group 2be, from an enzymological point of view, this
      enzyme might be differentiated from the enzymes in that group. Hybridization
      analysis revealed that beta-lactamase genes highly similar to blaRBI were
      generally encoded on the chromosome of the sulbactam-cefoperazone-resistant
      clinical isolates of K. oxytoca tested in the study, despite their different
      derivations. This observation suggests that sulbactam-cefoperazone-resistant A.
      oxytoca strains which produce RbiA-type beta-lactamases have been proliferating
      in many hospitals in Japan.

PMID- 8878569
TI  - Gamma radiation-sterilized, triple-lumen catheters coated with a low
      concentration of chlorhexidine were not efficacious at preventing catheter
      infections in intensive care unit patients.
AB  - In a randomized, double-blind trial, gamma radiation-sterilized, chlorhexidine
      coated triple-lumen catheters were compared with uncoated control catheters for
      their ability to prevent catheter infection in 254 intensive care unit patients.
      The chlorhexidine coating was not efficacious, and a rabbit model demonstrated
      that reduction of chlorhexidine activity by gamma radiation sterilization was the
      likely explanation for the failure.

PMID- 8878570
TI  - Comparison of a spectrophotometric microdilution method with RPMI-2% glucose with
      the National Committee for Clinical Laboratory Standards reference macrodilution
      method M27-P for in vitro susceptibility testing of amphotericin B, flucytosine,
      and fluconazole against Candida albicans.
AB  - The National Committee for Clinical Laboratory Standards has proposed a reference
      broth macrodilution method for in vitro antifungal susceptibility testing of
      yeasts (the M27-P method). This method is cumbersome and time-consuming and
      includes MIC endpoint determination by visual and subjective inspection of growth
      inhibition after 48 h of incubation. An alternative microdilution procedure was
      compared with the M27-P method for determination of the amphotericin B,
      flucytosine, and fluconazole susceptibilities of 8 American Type Culture
      Collection strains (6 of them were quality control or reference strains) and 50
      clinical isolates of candida albicans. This microdilution method uses as culture
      medium RPMI 1640 supplemented with 18 g of glucose per liter (RPMI-2% glucose).
      Preparation of drugs, basal medium, and inocula was done by following the
      recommendations of the National Committee for Clinical Laboratory Standards. The
      MIC endpoint was calculated objectively from the turbidimetric data read at 24 h.
      Increased growth of C. albicans in RPMI-2% glucose and its spectrophotometric
      reading allowed for the rapid (24 h) and objective calculation of MIC endpoints
      compared with previous microdilution methods with standard RPMI 1640.
      Nevertheless, good agreement was shown between the M27-P method and this
      microdilution test. The MICs obtained for the quality control or reference
      strains by the microdilution method were in the ranges published for those
      strains. For clinical isolates, the percentages of agreement were 100% for
      amphotericin B and fluconazole and 98.1% for flucytosine. These data suggest that
      this microdilution method may serve as a less subjective and more rapid
      alternative to the M27-P method for antifungal susceptibility testing of yeasts.

PMID- 8878571
TI  - Inhibition of human cytomegalovirus immediate-early gene expression by an
      antisense oligonucleotide complementary to immediate-early RNA.
AB  - ISIS 2922 is a phosphorothioate oligonucleotide that is complementary to human
      cytomegalovirus (CMV) immediate-early (IE) RNA and that exhibits potent and
      specific antiviral activity against CMV in cell culture assays. Specific assay
      systems were developed to separately characterize the antisense and nonantisense
      components of the antiviral activity mediated by ISIS 2922. In U373 cells
      transformed with cDNA encoding the CMV IE 55-kDa (IE55) protein, expression was
      inhibited at nanomolar concentrations comparable to effective concentrations in
      antiviral assays. The specificity of inhibition was demonstrated by using control
      oligonucleotides incorporating progressive base changes to destabilize
      oligonucleotide-RNA base pairing and by showing a lack of inhibition of the CMV
      IE72 product expressed from the same promoter. Inhibition of IE55 protein
      expression correlated with a reduction in mRNA levels consistent with an RNase H
      mediated termination event. Studies with virus-infected cells demonstrated that
      antisense and nonantisense mechanisms contribute to the antiviral activity of
      ISIS 2922. Base complementarity to target RNA was important for optimal activity
      in antiviral assays, but base changes affecting parameters other than
      hybridization affinity also influenced antiviral activity. Sequence-independent
      inhibition of virus adsorption to host cells by phosphorothioate oligonucleotides
      was also observed at high concentrations. Therefore, at least three different
      mechanisms may contribute to the antiviral activity of ISIS 2922 in cell culture:
      antisense-mediated inhibition of target gene expression; nonantisense, sequence
      dependent inhibition of virus replication; and sequence-independent inhibition of
      virus adsorption to host cells.

PMID- 8878572
TI  - Bacterial biofilms and the bioelectric effect.
AB  - Bacterial biofilms are acknowledged to be a major factor in problems of
      ineffective sterilization often encountered in clinics, hospitals, and industrial
      processes. There have been indications that the addition of a relatively small
      direct current electric field with the sterilant used to combat the biofilm
      greatly increases the efficacy of the sterilization process. The results of the
      experiments reported in this paper support the concept of the "bioelectric
      effect" as reported by J.W. Costerton, B. Ellis, K. Lam, F. Johnson, and A.E.
      Khoury (Antimicrob. Agents Chemother, 38:2803-2809, 1994). With a current of 1 mA
      flowing through the chamber containing the biofilm, an increase in the killing of
      the bacteria of about 8 log orders was observed at the end of 24 h (compared with
      the control with the same amount of antibacterial agent but no current). We also
      confirmed that the current alone does not affect the biofilm and that there
      appear to be optimum levels of both the current and the sterilant that are needed
      to obtain the maximum effect.

PMID- 8878573
TI  - In vitro and in vivo effects of rifabutin alone or combined with atovaquone
      against Toxoplasma gondii.
AB  - The efficacy of rifabutin (RIFA) alone or in combination with atovaquone (ATO)
      was examined in vitro and in a murine model of acute toxoplasmosis. In vitro
      studies were performed with MRC5 fibroblast tissue cultures, with quantification
      of Toxoplasma growth by enzyme-linked immunosorbent assay. For in vivo studies,
      mice were acutely infected with 10(4) tachyzoites of the virulent RH strain and
      were then treated perorally for 10 days from day 1 or day 4 postinfection. The
      efficacy of each drug regimen was assessed by determination of survival rates and
      sequential titration of parasites in blood, brain, and lungs by a tissue culture
      method. In vitro, RIFA was inhibitory for Toxoplasma growth at concentrations
      between 0.5 and 20 micrograms/ml; the 50% inhibitory concentration was estimated
      to be 1.68 micrograms/ml. When RIFA and ATO were combined, synergistic effects
      were noted for RIFA at 20 micrograms/ml combined with ATO at 0.01 or 0.02
      microgram/ml and RIFA at 1, 2, or 5 micrograms/ml combined with ATO at 0.02
      microgram/ml. In vivo, administration of RIFA at 200 mg/kg of body weight per day
      from day 1 to day 10 resulted in a 100% protection during treatment, with
      clearance of parasites from the blood, brain, and lungs. After the cessation of
      therapy, relapses occurred in the brain and lungs; the mortality was 46% at the
      end of the experiment (day 30). Among the mice treated with RIFA at 200 mg/kg/day
      from day 4 to day 14, no death was recorded during the treatment period and a
      marked reduction in parasite burdens was observed in blood and tissues; however,
      relapses occurred and 10% of mice survived until day 30. Administration of RIFA
      at 200 mg/kg/day in combination with ATO at 100 mg/kg/day resulted in a marked
      prolongation of survival compared with that for mice that received ATO or RIFA
      alone. However, in mice receiving the combination, parasite burdens in blood and
      organs were similar to those in mice treated with RIFA alone. These results
      confirmed the activity of RIFA in the treatment of acute toxoplasmosis and the
      potential of the combination of RIFA-ATO since the two drugs act synergistically
      against Toxoplasma gondii.

PMID- 8878574
TI  - Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas
      aeruginosa: mexR encodes a regulator of operon expression.
AB  - The region upstream of the multiple antibiotic resistance efflux operon mexA-mexB
      oprM in Pseudomonas aeruginosa was sequenced, and a gene, mexR, was identified.
      The predicted MexR product contains 147 amino acids with a molecular mass of
      16,964 Da, which is consistent with the observed size of the overexpressed mexR
      gene product. MexR was homologous to MarR, the repressor of MarA-dependent
      multidrug resistance in Escherichia coli, and other repressors of the MarR
      family. A mexR knockout mutant showed a twofold increase in expression of both
      plasmid-borne and chromosomal mexA-reporter gene fusions compared with the MexR+
      parent strain, indicating that the mexR gene product negatively regulates
      expression of the mexA-mexB-oprM operon. Furthermore, the cloned mexR gene
      product reduced expression of a plasmid-borne mexA-lacZ fusion in E. coli,
      indicating that MexR represses mexA-mexB-oprM expression directly. Consistent
      with the increased expression of the efflux operon in the mexR mutant, the mutant
      showed an increase (relative to its MexR+ parent) in resistance to several
      antimicrobial agents. Expression of a mexR-lacZ fusion increased threefold in a
      mexR knockout mutant, indicating that mexR is negatively autoregulated. OCR1, a
      nalB multidrug-resistant mutant which overproduces OprM, exhibited a greater than
      sevenfold increase in expression of a chromosomal mexA-phoA fusion compared with
      its parent. Introduction of a mexR knockout mutation in strain OCR1 eliminated
      this increase in efflux gene expression and, as expected, increased the
      susceptibility of the strain to a variety of antibiotics. The nucleotide
      sequences of the mexR genes of OCR1 and its parental strain revealed a single
      base substitution in the former which would cause a predicted substitution of Trp
      for Arg at position 69 of its mexR product. These data suggest that MexR
      possesses both repressor and activator function in vivo, the activator form being
      favored in nalB multidrug-resistant strains.

PMID- 8878575
TI  - A rob-like gene of Enterobacter cloacae affecting porin synthesis and
      susceptibility to multiple antibiotics.
AB  - A chromosomal gene of Enterobacter cloacae affecting the synthesis of major outer
      membrane proteins in E. cloacae and Escherichia coli was cloned by using
      selection for resistance to cefoxitin in E. coli. The presence of the gene, when
      plasmid-borne, led to a decrease in the amount of porin F in E. cloacae and the
      amount of OmpF in E. coli and caused 2- to 32-fold increases in the MICs of
      chloramphenicol, tetracycline, quinolones, and beta-lactam antibiotics. The gene
      encoded a 33-kDa protein, similar (83% identity) to the protein Rob involved in
      the initiation of DNA replication in E. coli, which was called RobA(EC1) by
      analogy. RobA from E. cloacae was found to inhibit ompF expression at the
      posttranscriptional level via activation of micF, a gene also apparently present
      in E. cloacae, as detected by PCR. As with its homolog from E. coli, RobA(EC1) is
      related to the XylS-AraC class of positive transcriptional regulators, along with
      MarA and SoxS, which also cause a micF-mediated decrease in the level of ampF
      expression.

PMID- 8878576
TI  - Native oligodeoxynucleotides specifically active against human immunodeficiency
      virus type 1 in vitro: a G-quartet-driven effect?
AB  - Among a series of unmodified phosphodiester (PO)-oligodeoxynucleotides (PO-ODNs)
      complementary to some of the human immunodeficiency virus type 1 (HIV-1)
      regulatory genes, several PO-ODN sequences complementary to the vpr gene (PO-ODNs
      a-vpr, where a-vpr is the antisense vpr sequence) emerged as potent inhibitors
      (at concentrations of 0.8 to 3.3 microM) of HIV-1 multiplication in de novo
      infected MT-4 cells, while they showed no cytotoxicity for uninfected cells at
      concentrations up to 100 microM. Unlike phosphorothioate counterparts, PO-ODN-a
      vpr sequences were not inhibitory to HIV-2 multiplication in de novo infected
      C8166 cells and neither prevented the fusion between chronically infected and
      bystander CD4+ cells nor inhibited the activity of the HIV-1 reverse
      transcriptase in enzyme assays. Moreover, they were not inhibitory to HIV-1
      multiplication in chronically infected cells. Delayed addition experiments showed
      that PO-ODNs-a-vpr inhibit an event in the HIV-1 replication cycle following
      adsorption to the host cell, but preceding reverse transcription. Structure
      activity relationship studies indicated that the antiviral activity of the test
      PO-ODN-a-vpr sequences is not related to an antisense mechanism but to the
      presence, within the active sequences, of contiguous guanine residues. Physical
      characterization of the test PO-ODNs suggested that the active structure is a
      tetramer stabilized by G quartets (i.e., four G residues connected by eight
      hydrogen bonds).

PMID- 8878577
TI  - Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on
      polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.
AB  - Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12
      volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and
      clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic
      functions and the release of reactive oxygen products following phagocytosis by
      neutrophil granulocytes prior to administration of the three drugs, 16 h after
      azithromycin administration, and 3 h after clarithromycin and roxithromycin
      administration. Phagocytic capacity was assessed by measuring the uptake of
      fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after
      phagocytosis of unlabeled bacteria was estimated by the amount of
      dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin
      resulted in decreased capacities of the cells to phagocytize Escherichia coli
      (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate
      reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01).
      Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control
      values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%]
      of the control values; P > 0.05). Roxithromycin treatment did not affect
      granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or
      reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No
      relation between intra- and/or extracellular concentrations of azithromycin
      and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive
      oxygen production existed (P > 0.05 for all comparisons). These results
      demonstrate that the accumulation of macrolides in neutrophils can suppress the
      response of phagocytic cells to bacterial pathogens after a therapeutic dose.

PMID- 8878578
TI  - Pharmacokinetic interaction between itraconazole and rifampin in Yucatan
      miniature pigs.
AB  - The objective of this study was to examine the effects of rifampin on
      itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs.
      Daily for 3 weeks, the pigs received 200 mg of itraconazole orally at the
      beginning of each meal, and for the following 2 weeks they received itraconazole
      orally combined with intravenous administration of rifampin at 10 mg/kg/day.
      Coadministration of rifampin resulted in an 18-fold decrease in the maximum
      concentration of itraconazole in serum, from 113.0 (standard deviation [SD] 17.2)
      to 6.2 (SD, 3.9) ng/ml and a 22-fold decrease in the area under the concentration
      time curve, from 1,652.7 (SD, 297.7) to 75.6 (SD, 30.0) ng.h/ml. The active
      metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study
      demonstrates that rifampin affects itraconazole kinetics considerably at steady
      state in this miniature-pig model, probably by inducing hepatic metabolism of
      itraconazole.

PMID- 8878579
TI  - Drug effects on intracellular mycobacteria determined by mass spectrometric
      analysis of the Na(+)-to-K+ ratios of individual bacterial organisms.
AB  - The successful establishment of a drug screening system for intracellular
      cultivable and noncultivable mycobacteria based on the mass spectrometric
      determination of bacterial viability is described. To compare drug efficacies on
      intra- and extracellular mycobacteria, the mycobacteria were subjected to drug
      treatment either after phagocytosis by the mouse macrophage cell line RAW 264.7
      or in cell-free medium. After reisolation, their viability was monitored by
      analyzing the intrabacterial sodium-to-potassium ratios for a limited number of
      individual organisms. This approach offers a reliable and quick tool for
      monitoring the influence of intracellular growth and of additional permeation
      barriers on intracellular drug efficacy and will thus provide useful information
      for the rational development and testing of optimized antimycobacterial drugs. In
      particular, the methodology is applicable to the noncultivable species
      Mycobacterium leprae, because the mass spectrometric analysis of the
      intrabacterial sodium-to-potassium ratio allows the determination of bacterial
      viability independent from their ability to multiply in vitro. Because of the
      improved metabolic activity of intracellularly growing M. leprae compared with
      that of extracellularly growing M. leprae, the spectrum of antileprosy drugs that
      can be tested in vitro could even be extended to those interfering with DNA
      replication and cell division.

PMID- 8878580
TI  - Sequence analysis, purification, and study of inhibition by 4-quinolones of the
      DNA gyrase from Mycobacterium smegmatis.
AB  - We determined the nucleotide sequence of a 6-kb DNA region harboring the recF,
      orf192, gyrB, and gyrA genes from Mycobacterium smegmatis mc(2)155. The amino
      acid sequences deduced from gyrA and gyrB displayed 89 and 86% identity,
      respectively, with the DNA gyrase from Mycobacterium tuberculosis, and 67 and 65%
      identity, respectively, with that from Streptomyces coelicolor. An open reading
      frame encoding the C-terminal region of the M. smegmatis RecF polypeptide was
      found upstream from gyrB and was 57% identical to the open reading frame encoding
      the C-terminal region of the S. coelicolor RecF protein. The gene orf192 was
      identified between recF and gyrB and was 39% identical to orf191 found in S.
      coelicolor in the recF-gyrB region. The M. smegmatis DNA gyrase, which was
      purified by affinity chromatography on novobiocin-Sepharose, consisted of two
      polypeptides with apparent molecular masses of 98 and 80 kDa. Determination of
      the N-terminal amino acid sequence of the B subunit confirmed GTG as the start
      codon in gyrB. Analysis of the supercoiling activity of the enzyme indicated that
      the M. smegmatis DNA gyrase was characterized by a specific activity equivalent
      to that of the Escherichia coli DNA gyrase. Inhibition of this activity by 4
      quinolones was investigated by determining the 50% inhibitory concentrations
      (IC50S) of nalidixic acid, ofloxacin, and ciprofloxacin. The results indicated
      that the inhibitory activities of these drugs against the M. smegmatis DNA gyrase
      were markedly lower than those previously reported for the E. coli DNA gyrase.
      The results also suggested that the higher levels of activity of ofloxacin and
      ciprofloxacin against M. smegmatis (MICs, 0.5 to 1 microgram/ml), in contrast to
      that of nalidixic acid (MIC, 256 micrograms/ml), could be related to the higher
      inhibitory activities of fluoroquinolones against the DNA gyrase from this
      species (IC50S, 7 to 14 micrograms/ml) compared with that of nalidixic acid
      (IC50, 1,400 micrograms/ml).

PMID- 8878581
TI  - In vivo activity and pharmacodynamics of amoxicillin in combination with
      fosfomycin in fibrin clots infected with highly penicillin-resistant
      Streptococcus pneumoniae.
AB  - Using a clinical pneumococcal strain for which MICs were 4, 2, and 32 mg/liter
      for penicillin, amoxicillin, and fosfomycin, respectively, we studied the
      efficacies of these antibiotics alone and their combinations in the treatment of
      prolonged (48-h) experimental fibrin clot infection in rabbits. Treatments were
      as follows: amoxicillin IV at 20 mg/kg of body weight in one dose (Amo20), 50
      mg/kg in one dose (Amo50), or two doses 6 h apart (Amo20 x 2 and Amo50 x 2);
      fosfomycin IV at a fixed dose of 50 mg/kg in one dose (Fos50) or two divided
      doses 6 h apart (Fos50 x 2); or the combinations of amoxicillin and fosfomycin
      with the same schedules. Maximum concentrations in clots were 2.03 +/- 1.02 and
      2.13 +/- 0.33 mg/liter for Amo20 regimens, 3.7 +/- 1.9 and 4 +/- 1.3 mg/liter for
      Amo50 regimens, and 24 +/- 7 and 40 +/- 8 mg/liter for fosfomycin regimens,
      respectively. The mean half-lives of elimination from clots were between 2 and 3
      h for amoxicillin regimens and between 5 and 7 h for fosfomycin. We observed the
      highest bacterial reductions (log10 CFU/gram) for Amo50 in two divided doses with
      or without fosfomycin. A significantly higher bacterial reduction than that with
      each monotherapy was observed when Amo20 was combined with fosfomycin in either
      one dose or two doses 6 h apart (0.16 +/- 0.8 and 1.64 +/- 1.6 log10 CFU/g for
      Amo20 in one and two doses, respectively, and 0.93 +/- 0.81 and 0.61 +/- 0.56
      log10 CFU/g for fosfomycin in one and two doses, respectively, versus 3.46 +/-
      1.26 and 3.16 +/- 1.31 log10 CFU/g for Amo20 plus fosfomycin in one and two
      doses, respectively [P < 0.001]). A time-dependent effect was observed with
      amoxicillin regimens. The time of regrowth was significantly delayed when
      amoxicillin was combined with fosfomycin. By using a multivariate analysis, we
      demonstrated that the most important parameter correlated to efficacy of the
      combination amoxicillin-fosfomycin was the length of the period during which the
      concentration of amoxicillin remained above the MIC. We demonstrated that the in
      vivo efficacy of the combination of amoxicillin and fosfomycin gave higher
      antibacterial effect than each monotherapy.

PMID- 8878582
TI  - Combination of PS-15, epiroprim, or pyrimethamine with dapsone in prophylaxis of
      Toxoplasma gondii and Pneumocystis carinii dual infection in a rat model.
AB  - In a rat model of dual infection, we studied such dihydrofolate reductase (DHFR)
      inhibitors as PS-15 (25 mg/kg of body weight), epiroprim (100 mg/kg), and
      pyrimethamine (3 mg/kg) alone or in combination with various doses of dapsone
      (50, 25, or 5 mg/kg) for the prevention of pneumocystosis and toxoplasmosis. Rats
      latently infected with Pneumocystis carinii were immunosuppressed by
      corticosteroids for 7 weeks, and the drugs were administered from the initiation
      of the corticosteroid treatment. At week 5, the rats were inoculated
      intraperitoneally with the RH strain of Toxoplasma gondii. Infections were
      monitored by the counting of P. carinii cysts in lung homogenates and the
      titration of T. gondii in organs by quantitative culture and an indirect
      immunofluorescence assay. Fourteen of the 15 untreated rats died after T. gondii
      challenge, with P. carinii infection in the lungs and T. gondii infection in the
      lungs, liver, spleen, and brain. Of the three tested DHFR inhibitors, only PS-15
      exhibited anti-P. carinii activity; none prevented toxoplasmosis in 100% of the
      rats. After the DHFR inhibitors were combined with dapsone (50 or 25 mg/kg), both
      pneumocystosis and toxoplasmosis were completely prevented. On the basis of these
      results, PS-15 and epiroprim combined with dapsone are candidates for use for the
      prevention of both pneumocystosis and toxoplasmosis.

PMID- 8878583
TI  - MIC and time-kill study of antipneumococcal activities of RPR 106972 (a new oral
      streptogramin), RP 59500 (quinupristin-dalfopristin), pyostacine (RP 7293),
      penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin
      susceptible and -resistant pneumococci.
AB  - Broth MICs and time-kill studies were used to test the activity of RP 59500
      (quinupristin-dalfopristin), RPR 106972, pyostacine (RP 7293), erythromycin,
      clarithromycin, and cefotaxime for four penicillin-susceptible (MICs of 0.008 to
      0.03 microgram/ml), two penicillin-intermediate (MIC of 0.25 microgram/ml), and
      four penicillin-resistant (MIC of 2.0 to 4.0 micrograms/ml) strains of
      pneumococci: 6 of 10 strains were resistant to macrolides (MICs of > or = 0.5
      microgram/ml). MICs of RP 59500 (0.5 to 1.0 microgram/ml), RPR 106972 (0.125 to
      0.25 microgram/ml), and pyostacine (0.125 to 0.25 microgram/ml) did not alter
      with the strain's penicillin or macrolide susceptibility status. Three penicillin
      susceptible strains and one penicillin-intermediate strain were susceptible to
      macrolides (MICs of < or = 0.25 microgram/ml); the macrolide MICs for the
      remaining strains were > or = 4.0 micrograms/ml. Cefotaxime MICs rose with those
      of penicillin G, but all strains were inhibited at MICs of < or = 2.0
      micrograms/ml. RP 59500 was bactericidal for all strains after 24 h at 2 x MIC
      and yielded 90% killing of all strains at 6 h at 2 x MIC; at 8 x MIC, RP 59500
      showed 90% killing of six strains within 10 min (approximately 0.2 h). In
      comparison, RPR 106972 was bactericidal for 9 of 10 strains at 2 x MIC after 24 h
      and yielded 90% killing of all strains at 2 x MIC after 6 h; 90% killing of six
      strains was found at 8 x MIC at 0.2 h. Results for pyostacine were similar to
      those of RPR 106972. Erythromycin and clarithromycin were bactericidal for three
      of four macrolide-susceptible strains after 24 h at 4 x MIC. Clarithromycin
      yielded 90% killing of three strains at 8 x MIC after 12 h. Cefotaxime was
      bactericidal for all strains after 24 h at 4 x MIC, yielding 90% killing of all
      strains after 6 h at 4 x MIC. All three streptogramins yielded rapid killing of
      penicillin- and erythromycin-susceptible and -resistant pneumococci and were the
      only compounds which killed significant numbers of strains at 0.2 h.

PMID- 8878584
TI  - Specific interaction between beta-lactams and soluble penicillin-binding protein
      2a from methicillin-resistant Staphylococcus aureus: development of a chromogenic
      assay.
AB  - We investigated the enzymatic acylation of penicillin-binding protein 2a (PBP 2a)
      from methicillin-resistant Staphylococcus aureus by beta-lactams. Using a
      purified, soluble form of the protein (PBP 2a'), we observed beta-lactam-induced
      in vitro precipitation following first-order kinetics with respect to protein
      concentration. We used electrospray mass ionization spectrometry to show that the
      protein precipitate predominantly contained PBP 2a', with the beta-lactam bound
      to it in a 1:1 molar ratio. Using nitrocefin, a chromogenic beta-lactam, we
      confirmed the correlation between PBP 2a' precipitation and its beta-lactam
      dependent enzymatic acylation by monitoring the absorbance associated with the
      precipitate. Finally, dissolving the precipitate in urea, we developed a simple
      in vitro chromogenic assay to monitor beta-lactam-dependent enzymatic acylation
      of PBP 2a'. This assay represents a significant improvement over the traditional
      radioactive penicillin-binding assay.

PMID- 8878585
TI  - Characterization of IMI-1 beta-lactamase, a class A carbapenem-hydrolyzing enzyme
      from Enterobacter cloacae.
AB  - In 1984, a year prior to the U.S. approval of imipenem for clinical use, a wound
      isolate and a bile isolate of Enterobacter cloacae were obtained from two
      patients in a California hospital. These isolates were resistant to imipenem,
      penicillins, and inhibitor combinations; early cephalosporins such as
      cephalothin, cefamandole, and cefoxitin; and cefoperazone. However, they were
      susceptible (MICs, < 4 micrograms/ml) to cefotaxime, ceftriaxone, ceftazidime,
      and moxalactam. Both strains produced an apparent TEM-1 beta-lactamase; an
      inducible NmcA-type imipenem-hydrolyzing beta-lactamase, IMI-1, with a pl of
      7.05; and an inducible beta-lactamase with a pI of 8.1, typical of an E. cloacae
      AmpC beta-lactamase. Purified IMI-1 hydrolyzed imipenem and benzylpenicillin at
      modest rates, but more slowly than cephaloridine. The enzyme was inhibited by
      clavulanic acid and tazobactam. EDTA did not inhibit the cephaloridine
      hydrolyzing activity. The beta-lactamase gene encoding IMI-1, imiA1, was cloned
      from E. cloacae 1413B. Sequence analysis identified the imiA1 gene as encoding a
      class A serine beta-lactamase. Both the imiA1 DNA and encoded amino acid
      sequences shared greater than 95% identity with the NmcA gene and its encoded
      protein. DNA sequence analysis also identified a gene upstream of imiA1 that
      shares > 95% identity with nmcR and that may encode a regulatory protein. In
      conclusion, IMI-1, a carbapenem-hydrolyzing beta-lactamase inhibited by
      clavulanic acid, was identified as a group 2f, class A, carbapenem-hydrolyzing
      cephalosporinase.

PMID- 8878586
TI  - Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.
AB  - Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H)
      and pseudohypericin (PH) were studied in 13 healthy volunteers by administration
      of St. John's Wort extract LI 160, a plantal antidepressant. Oral administration
      of 250, 750, and 1,500 micrograms of H and 526, 1,578, and 3,156 micrograms of PH
      resulted in median peak levels in plasma (Cmax) of 1.3, 7.2, and 16.6
      micrograms/liter for H and 3.4, 12.1, and 29.7 micrograms/liter for PH,
      respectively. The Cmax and the area under the curve values for the lowest dose
      were disproportionally lower than those for the higher doses. A lag time of 1.9 h
      for H was remarkably longer than the 0.4-h lag time for PH. Median half-lives for
      absorption, distribution, and elimination were 0.6, 6.0, and 43.1 h after 750
      micrograms of H and 1.3, 1.4, and 24.8 h after 1,578 micrograms of PH,
      respectively. Fourteen-day treatment with 250 micrograms of H and 526 micrograms
      of PH three times a day resulted in median steady-state trough levels of 7.9
      micrograms/liter for H and 4.8 micrograms/liter for PH after 7 and 4 days,
      respectively; the corresponding Cssmax levels were 8.8 and 8.5 micrograms/liter,
      respectively. Kinetic parameters after intravenous administration of Hypericum
      extract (115 and 38 micrograms for H and PH, respectively) in two subjects
      corresponded to those estimated after an oral dosage. Both H and PH were
      initially distributed into a central volume of 4.2 and 5.0 liter, respectively.
      The mean distribution volumes at steady state were 19.7 liters for H and 39.3
      liters for PH, and the mean total clearance rates were 9.2 ml/min for H and 43.3
      ml/min for PH. The systemic availability of H and PH from LI 160 was roughly
      estimated to be 14 and 21%, respectively. Treatment with Hypericum extract, even
      in high doses, was well tolerated.

PMID- 8878587
TI  - In vitro activities of novel catecholate siderophores against Plasmodium
      falciparum.
AB  - The activities of novel iron chelators, alone and in combination with
      chloroquine, quinine, or artemether, were evaluated in vitro against susceptible
      and resistant clones of Plasmodium falciparum with a semimicroassay system. N4
      nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7)
      demonstrated the highest level of activity: 170 nM against a chloroquine
      susceptible clone and 1 microM against a chloroquine-resistant clone (50%
      inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity
      with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on
      the activities of chloroquine, quinine, and artemether against either clone, and
      compound 8 did not enhance the schizontocidal action of either chloroquine or
      quinine against the chloroquine-resistant clone. The incubation of compound 7
      with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound
      7, while no effect was observed with incubation of compound 7 with CuSO4 and
      ZnSO4. These results suggest that iron deprivation may be the main mechanism of
      action of compound 7 against the malarial parasites. Chelator compounds 7 and 8
      primarily affected trophozoite stages, probably by influencing the activity of
      ribonucleotide reductase, and thus inhibiting DNA synthesis.

PMID- 8878588
TI  - Antimicrobial activity of human pancreatic juice and its interaction with
      antibiotics.
AB  - Pancreatic juice (PJ) should be a factor of variability in the antimicrobial
      activity of antibiotics eliminated by the pancreas during pancreatic infections.
      We studied its effects on the activity of antimicrobial drugs with different
      mechanisms of action. Samples of pure PJ were collected from 16 patients with
      stabilized external pancreatic fistulas. The antimicrobial activity of the juice
      at different concentrations (from 1.25 to 100%) alone and in combination with
      mezlocillin, imipenem, ceftriaxone, gentamicin, ofloxacin, and ciprofloxacin was
      studied by a microbiological method (continuous turbidimetric recording of
      bacterial growth). The human PJ showed dose-dependent antimicrobial activity that
      increased directly with the concentration. The activity of the antibiotics at
      bactericidal concentrations were not modified by the PJ, while the combination
      with subinhibitory concentrations produced the following variable and different
      effects: (i) additivity with mezlocillin, ceftriaxone, gentamicin, and
      ciprofloxacin and autonomy (no interaction) with imipenem and ofloxacin against
      Providencia rettgeri and (ii) additivity with ceftriaxone, ofloxacin, gentamicin,
      imipenem, and mezlocillin and autonomy with ciprofloxacin against Escherichia
      coli. In the presence of PJ, fluoroquinolones showed constant positive effects,
      while beta-lactams showed more variable antimicrobial activity. Antibiotic
      concentrations and PJ pharmacodynamics are the main factors determining the final
      effect of the interaction in vitro. These results may be useful in choosing
      antibiotics for the treatment of pancreatic infections when they are supplemented
      with the pharmacokinetic data for each drug.

PMID- 8878589
TI  - Comparison study of broth macrodilution and microdilution antifungal
      susceptibility tests for the filamentous fungi.
AB  - An evaluation of broth dilution antifungal susceptibility tests was performed by
      determining both the micro- and macrodilution MICs of amphotericin B,
      fluconazole, ketoconazole, 5-fluorocytosine, miconazole, and itraconazole against
      representative species of opportunistic hyphomycetes (Fusarium spp. and
      Cladosporium [Cladophialophora] spp.) and ascomycetes (Chaetomium spp.). A total
      of 78 strains were tested, the majority of them twice and some three times on
      different days. Both methods were performed according to the recommendations of
      the National Committee for Clinical Laboratory Standards (Document M27-P), with
      the exception of the temperature of incubation, which was 25 degrees C in our
      case. A spectrophotometric method for inoculum preparation, RPMI 1640 medium
      buffered with morpholinepropanesulfonic acid (pH 7.0), and an additive drug
      dilution procedure were used. The MICs obtained by the two methods were read
      after 48, 72, and 96 h of incubation for Fusarium spp. and after 72, 96, and 120
      h for the remaining isolates. The kappa test was used to calculate the degree of
      agreement. Considering the three fungal groups together, a good agreement between
      the results of both tests was observed with almost all the drugs at the different
      incubation times. There were no cases of poor agreement. The highest level (kappa
      index = 1) was observed with ketoconazole at the second-day reading. These
      results support the further evaluation of the broth microdilution test as an
      alternative to the reference broth macrodilution susceptibility test.

PMID- 8878590
TI  - Efficacy of sparfloxacin and autoradiographic diffusion pattern of
      [14C]Sparfloxacin in experimental Staphylococcus aureus joint prosthesis
      infection.
AB  - Using a new rabbit model of methicillin-susceptible Staphylococcus aureus knee
      prosthesis infection, we compared the efficacies of sparfloxacin (50 mg/kg of
      body weight subcutaneously, twice a day) and pefloxacin (50 mg/kg subcutaneously,
      twice a day). A partial knee replacement was performed with a silicone implant
      fitted into the intramedullary canal of the tibia, and 5 x 10(7) CFU of
      methicillin-susceptible S. aureus was injected into the knee. The 7-day treatment
      regimen was started 15 days later. The MICs and MBCs of sparfloxacin and
      pefloxacin were, respectively, 0.06 and 0.25 microgram/ml (MIC) and 0.25 and 1
      microgram/ml (MBC). The peak levels of sparfloxacin and pefloxacin in serum were
      3.6 and 21 micrograms/ml, respectively. Three weeks after the end of treatment,
      animals were sacrificed and tibias were removed, pulverized, and quantitatively
      cultured. In contrast to pefloxacin (3.61 +/- 1.64 log10 CFU/g of bone),
      sparfloxacin significantly reduced the bacterial density (2.12 +/- 1.1 log10
      CFU/g of bone) (P = 0.01) in comparison with the level in controls (4.59 +/- 1.21
      log10 CFU/g of bone), without selection of resistant variants. Sparfloxacin was
      significantly more effective than pefloxacin (P = 0.025). The autoradiographic
      pattern of [14C]sparfloxacin diffusion was studied in noninfected animals with
      prostheses and in infected animals 15 days after inoculation. Sixty minutes after
      completion of infusion of 250 microCi of [14C]sparfloxacin, in infected animals
      the highest levels of radioactivity were detected around the prosthesis, in
      femoral cartilage, and in articular ligaments. Radioactivity was slightly less
      intense in bone marrow and muscles and was very weak in compact bone. The
      distribution of sparfloxacin in uninfected rabbits was similar. Thus,
      sparfloxacin may represent a valid alternative therapy in these infections
      provided that it is carefully monitored for potential side effects.

PMID- 8878591
TI  - In vitro activities of eight macrolide antibiotics and RP-59500 (quinupristin
      dalfopristin) against viridans group streptococci isolated from blood of
      neutropenic cancer patients.
AB  - From January 1988 to December 1994, 66 consecutive blood culture isolates of
      viridans group streptococci collected from febrile neutropenic cancer patients
      were tested for antimicrobial susceptibilities by the agar dilution method. The
      antibiotics studied were erythromycin, clarithromycin, roxithromycin,
      dirithromycin, azithromycin, josamycin, diacetyl-midecamycin, spiramycin, and
      quinupristin-dalfopristin. A total of 26 (39.4%) strains were resistant to
      erythromycin with an MIC range of 0.5 to > 128 micrograms/ml. The strains were
      classified into three groups according to their penicillin susceptibility: 42
      (63.6%) were susceptible, 8 (12.1%) were intermediately resistant, and 16 (24.3%)
      were highly resistant. The percentages of erythromycin-resistant strains in each
      group were 23.8, 62.5, and 68.8%, respectively. Streptococcus mitis was the
      species most frequently isolated (83.3%) and showed the highest rates of
      penicillin (40%) and erythromycin (43.6%) resistance. MICs of all macrolide
      antibiotics tested and of quinupristin-dalfopristin were higher for penicillin
      resistant strains than for penicillin-susceptible strains. All macrolide
      antibiotics tested had cross-resistance to erythromycin, which was not observed
      with quinupristin-dalfopristin. Our study shows a high rate of macrolide
      resistance among viridans group streptococci isolated from blood samples of
      neutropenic cancer patients, especially those infected with penicillin-resistant
      strains. These findings make macrolides unsuitable prophylactic agents against
      viridans group streptococcal bacteremia in this patient population.

PMID- 8878592
TI  - Penicillin-binding protein 4 overproduction increases beta-lactam resistance in
      Staphylococcus aureus.
AB  - The Staphylococcus aureus mutant strain PVI selected in vitro for methicillin
      resistance overexpressed penicillin-binding protein (PBP) 4. In the wild-type
      parent strain the pbp4 gene was separated by 419 nucleotides from a divergently
      transcribed abcA locus coding for an ATP-binding cassette transporter. The mutant
      PVI was shown to have a deletion in the pbp4-abcA promoter region that affected
      pbp4 transcription but not expression of abcA. Introduction of the pbp4 gene plus
      the mutant promoter region into different genetic backgrounds revealed that PBP 4
      overproduction was sufficient to increase in vitro-acquired methicillin
      resistance independently of other chromosomal genes. The role of the AbcA
      transporter in methicillin resistance remained unknown.

PMID- 8878593
TI  - Intestinal elimination of ofloxacin enantiomers in the rat: evidence of a carrier
      mediated process.
AB  - The aim of this work was to examine the mechanism involved in intestinal
      elimination of the two optical isomers of ofloxacin in the rat. An intestinal
      segment was isolated in situ and perfused with saline, while drug solution was
      administered via the carotid artery. Blood samples and intestinal effluents were
      collected and analyzed by a high-performance liquid chromatography method. We
      observed saturable and stereoselective intestinal elimination of the ofloxacin
      enantiomers. The elimination process favored the R-(+) form of the molecule.
      After a parenteral dose of 20 mg of racemic ofloxacin per kg of body weight,
      intestinal clearances were 0.23 +/- 0.03 versus 0.30 +/- 0.03 ml/min for S-(-)-
      and R-(+)-ofloxacin, respectively. Ciprofloxacin and pefloxacin interfered with
      ofloxacin elimination and significantly reduced the intestinal clearance of S-(-)
      and R-(+)-ofloxacin. With concomitant ciprofloxacin, intestinal clearances
      became 0.13 +/- 0.02 versus 0.17 +/- 0.03 ml/min and 0.14 +/- 0.01 versus 0.19 +/
      0.05 ml/min with pefloxacin for S-(-)- and R-(+)-ofloxacin, respectively. Those
      findings argue for the presence of a common transport system in the rat intestine
      with variable affinities for fluoroquinolones. In addition, verapamil and
      quinidine, two P-glycoprotein blockers, significantly reduced the intestinal
      elimination of both ofloxacin isomers (with concomitant verapamil, intestinal
      clearances were 0.12 +/- 0.02 versus 0.18 +/- 0.03 ml/min for S-(-)- and R-(+)
      ofloxacin, respectively, while with concomitant quinidine, values were 0.18 +/-
      0.01 versus 0.23 +/- 0.01 ml/min without modifying their areas under the
      concentration-time curve in serum. Similar results were found with another
      fluoroquinolone, ciprofloxacin, in previous work. P-glycoprotein appears to be
      involved in the intestinal elimination of fluoroquinolones in rats. The
      characterization of fluoroquinolone intestinal elimination has significant
      clinical relevance for the better evaluation of the influence of this secretory
      pathway on antibiotic efficacy and selection of resistant bacteria within the
      intestinal flora.

PMID- 8878594
TI  - Genetic characterization of trimethoprim resistance in Haemophilus influenzae.
AB  - We previously demonstrated that trimethoprim (Tmp) resistance in Haemophilus
      influenzae is mediated by chromosomally encoded dihydrofolate reductase (DHFR)
      with a modified primary structure and distinct kinetic properties. To gain
      insight into the relationship of the DHFR structure and the level of Tmp
      resistance that it confers on the host bacterium, we cloned and characterized the
      folH genes of one Tmp-susceptible and two Tmp-resistant H. influenzae strains.
      Differences were observed between Tmp-susceptible and Tmp-resistant isolates both
      in the promoter region and in the coding sequences. The effect of differences
      between H. influenzae folH genes on Tmp susceptibility was investigated in
      Escherichia coli. Various folH gene hybrids were constructed, and their influence
      on Tmp susceptibility was determined. Resistance in E. coli mediated by folH from
      H. influenzae strain R1047 was associated with alterations in the promoter and
      the central part of folH. In contrast, the E. coli Tmp resistance phenotype
      associated with the folH gene of H. influenzae R1042 was characterized by
      alterations in one or more of three amino acid residues at the C-terminal part of
      the protein. These data indicate that Tmp resistance is not only related to
      alterations in the promoter region of the folH gene and the Tmp binding domains
      at the N-terminal and central part of DHFR. Alterations in the C-terminal part
      may also cause Tmp resistance, probably as a result of a change in secondary
      structure and the subsequent loss of Tmp binding affinity.

PMID- 8878595
TI  - Bactericidal activity of single dose of clarithromycin plus minocycline, with or
      without ofloxacin, against Mycobacterium leprae in patients.
AB  - Fifty patients with newly diagnosed lepromatous leprosy were allocated randomly
      to one of five groups and treated with either a month-long standard regimen of
      multidrug therapy (MDT) for multibacillary leprosy, a single dose of 600 mg of
      rifampin, a month-long regimen with the dapsone (DDS) and clofazimine (CLO)
      components of the standard MDT, or a single dose of 2,000 mg of clarithromycin
      (CLARI) plus 200 mg of minocycline (MINO), with or without the addition of 800 mg
      of ofloxacin (OFLO). At the end of 1 month, clinical improvement accompanied by
      significant decreases of morphological indexes in skin smears was observed in
      about half of the patients of each group. A significant bactericidal effect was
      demonstrated in the great majority of patients in all five groups by inoculating
      the footpads of mice with organisms recovered from biopsy samples obtained before
      and after treatment. Rifampin proved to be a bactericidal drug against
      Mycobacterium leprae more potent than any combination of the other drugs. A
      single dose of CLARI-MINO, with or without OFLO, displayed a degree of
      bactericidal activity similar to that of a regimen daily of doses of DDS-CLO for
      1 month, suggesting that it may be possible to replace the DDS and CLO components
      of the MDT with a monthly dose of CLARI-MINO, with or without OFLO. However,
      gastrointestinal adverse events were quite frequent among patients treated with
      CLARI-MINO, with or without OFLO, and may be attributed to the higher dosage of
      CLARI or MINO or to the combination of CLARI-MINO plus OFLO. In future trials,
      therefore, we propose to reduce the dosages of the drugs to 1,000 mg of CLARI,
      100 mg of MINO, and 400 mg of OFLO.

PMID- 8878596
TI  - In vitro activity of the trinem sanfetrinem (GV104326) against gram-positive
      organisms.
AB  - The in vitro activity of the trinem sanfetrinem (formerly GV104326) (GV) was
      compared with that of vancomycin, ampicillin, and/or nafcillin against 287 gram
      positive bacteria, including methicillin-resistant Staphylococcus aureus and
      multiresistant enterococci, by the agar and microbroth dilution methods. GV
      demonstrated 2 to 16 times more activity than ampicillin and nafcillin against
      the majority of these organisms. The MIC range of GV was 16 to 64 micrograms/ml
      for 19 Enterococcus faecium strains that were highly resistant to ampicillin
      (ampicillin MIC range, 64 to 512 micrograms/ml) and vancomycin resistant and 0.25
      to 32 micrograms/ml for resistant Rhodococcus spp. Similar activities (+/-1
      dilution) were observed by either the agar or the broth microdilution method. GV
      demonstrated bactericidal activity against a beta-lactamase-producing
      Enterococcus faecalis strain and against two methicillin-susceptible
      Staphylococcus aureus strains in 10(5)-CFU/ml inocula. Synergy between GV and
      gentamicin was observed against an E. faecalis strain that lacked high-level
      gentamicin resistance. The activity of GV suggests this compound warrants further
      study.

PMID- 8878597
TI  - Synergy between amoxicillin and gentamicin in combination against a highly
      penicillin-resistant and -tolerant strain of Streptococcus pneumoniae in a mouse
      pneumonia model.
AB  - In vivo synergy with beta-lactam antibiotics and aminoglycosides has been studied
      only with penicillin-susceptible Streptococcus pneumoniae strains. We evaluated
      the interaction between amoxicillin (AMX) and gentamicin (GEN) on the basis of in
      vitro checkerboard and time-kill curves and of findings in a mouse model of acute
      bacteremic pneumonia due to a highly penicillin-resistant and -tolerant S.
      pneumoniae strain of serotype 19 (penicillin and AMX MICs of 4 micrograms/ml;
      gentamicin MIC of 16 micrograms/ml). Checkerboard results at 18 h of incubation
      showed indifference. With regard to AMX alone, in vitro time-kill curves
      demonstrated synergy between AMX (1 microgram/ml) and GEN (16 micrograms/ml) at 5
      and 8 h of incubation and for AMX (16 micrograms/ml) in combination with GEN (16
      micrograms/ml) at 3, 5, and 8 h of incubation. In leukopenic mice, pulmonary
      killing curves after a single drug injection demonstrated that AMX (100 mg/kg of
      body weight) with GEN (16 mg/kg) was more effective than AMX alone (P = 10(-4).
      With repeated-dose treatment, a synergy was apparent at 8 h after four injections
      with AMX (100 mg/kg) in combination with GEN (8 or 16 mg/kg) (P < or = 0.05). The
      cumulative survival rate with AMX (100 mg/kg) every 8 h, combined with GEN (4 or
      8 mg/kg) every 8, 12, or 24 h, was better than with AMX alone. Combined use of
      AMX and GEN may be a valuable therapeutic alternative for pneumococcal pneumonia
      due to highly penicillin-resistant S. pneumoniae strains.

PMID- 8878598
TI  - Recovery of active beta-lactamases from Proteus vulgaris and RTEM-1 hybrid by
      random mutagenesis by using a dnaQ strain of Escherichia coli.
AB  - Proteus vulgaris and RTEM-1 beta-lactamases that belong to molecular class A with
      37% amino acid similarity were examined to find the relationship between amino
      acid residues and activity of enzymes. MICs of ampicillin were > 2,000
      micrograms/ml for Escherichia coli cells producing these enzymes. We have made 18
      hybrid genes by substituting the coding region of the P. vulgaris beta-lactamase
      gene with the equivalent portions from the RTEM-1 gene. Most of these hybrids
      produced inactive proteins, but a few hybrid enzymes had partial or trace
      activity. From one of the hybrid genes (MIC of ampicillin, 100 micrograms/ml), we
      recovered three kinds of active mutants which provided ampicillin MICs of 1,000
      micrograms/ml by the selection of spontaneous mutations in a dnaQ strain of E.
      coli. In these mutants, Leu-148, Met-182, and Tyr-274 were replaced with Val,
      Thr, and His, respectively. These amino acids have not been identified as
      residues with functional roles in substrate hydrolysis. Furthermore, from these
      hybrid mutants, we obtained a second set of mutants which conferred ampicillin
      MICs of 1,500 micrograms/ml. Interestingly, the second mutations were limited to
      these three amino acid substitutions. These amino acid residues which do not
      directly interact with substrates have an effect on enzyme activity. These mutant
      enzymes exhibited lower K(m) values for cephaloridine than both parental enzymes.

PMID- 8878599
TI  - Chemical Determinants of antimalarial activity of reversed siderophores.
AB  - Reversed siderophores (RSFs) are artificial hydroxamate-based iron chelators
      designed after the natural siderophore ferrichrome. The modular molecular design
      of RSF derivatives allowed the synthesis of various congeners with controlled
      iron-binding capacities and partition coefficients. These two physicochemical
      properties were assessed by a novel fluorescent method and were found to be the
      major determinants of RSF permeation across erythrocyte membranes and scavenging
      of compartmentalized iron. The partition coefficient apparently conferred upon
      RSFs two major features: (i) the ability to rapidly access iron pools of in vitro
      grown Plasmodium falciparum at all developmental stages and to mobilize
      intracellular iron and transfer it to the medium and (ii) the ability to suppress
      parasite growth at all developmental stages. These features of RSFs were assessed
      by quantitative determination of the structure-activity relationships of the
      biological activities and partition coefficients spanning a wide range of values.
      The most effective RSF containing the aromatic group of phenylalanine (RSFm2phe)
      showed 50% inhibitory concentration of 0.60 +/- 0.03 nmol/ml in a 48-h test and a
      2-h onset of inhibition of ring development at 5 nmol/ml. The lipophilic compound
      RSFm2phe and the lipophilic and esterase-cleavable compound RSFm2pee inhibited
      parasite growth at all developmental stages whether inhibition was assessed in a
      continuous mode or after discontinuing drug administration. The antimalarial
      effects of RSFm2phe and cleavable RSFm2pee were potentiated in the presence of
      desferrioxamine (DFO) at concentrations at which DFO alone had no effect on
      parasite growth. These studies provide experimental evidence indicating that the
      effective and persistent antimalarial actions of RSFs are associated with drug
      access to infected cells and scavenging of iron from intracellular parasites.
      Moreover, the optimal antimalarial actions of RSFs are apparently also determined
      by improved accessibility to critical iron pools or by specific interactions with
      critical parasite targets.

PMID- 8878600
TI  - Pharmacokinetics of oral and intravenous ofloxacin in children with multidrug
      resistant typhoid fever.
AB  - The pharmacokinetics of oral and intravenous ofloxacin (7.5 mg.kg of body weight
      1 given over 30 min) were studied in an open crossover study of 17 Vietnamese
      children, aged between 5 and 14 years, with acute uncomplicated typhoid fever.
      Following oral administration, the median (95% confidence interval [CI]) time to
      peak concentration of ofloxacin in serum (Cmax) was 1.7 h (1.4 to 1.9 h) and the
      mean (95% CI) Cmax was 5.5 mg.liter-1 (4.7 to 6.3 mg.liter-1) compared with a
      Cmax of 8.7 mg.liter-1 (7.6 to 9.7 mg.liter-1) following the intravenous
      infusion. The median (95% CI) total apparent volume of distribution following the
      first intravenous dose, 1.35 liter.kg-1 (1.17 to 1.73 liter.kg-1), was
      significantly larger than that following the second dose, 0.99 liter.kg-1 (0.86
      to 1.17 liter.kg-1; P < 0.0005), although the estimates for systemic clearance
      were similar: 0.255 liter.kg-1 h-1 (0.147 to 0.325 liter.kg-1 h-1) compared with
      0.172 liter.kg-1 h-1 (0.127 to 0.292 liter.kg-1 h-1; P = 0.14). The mean
      residence times (95% CI) following intravenous and oral administration were
      similar: 5.24 h (4.84 to 6.58 h) and 6.24 h (5.32 to 7.85 h), respectively. The
      mean (95% CI) oral bioavailability was 91% (74 to 109%). The peak concentrations
      in serum were 10 to 100 times higher than the maximum MICs for ofloxacin against
      multidrug-resistant Salmonella typhi isolated in this area. Although the systemic
      clearance values were higher than those reported previously for adults, these
      data overall suggest that weight-or area-adjusted dose regimens for the treatment
      of typhoid in older children should be the same as those for adults.

PMID- 8878601
TI  - Location of N-acetylmuramyl-L-alanyl-D-glutamylmesodiaminopimelic acid, presumed
      signal molecule for beta-lactamase induction, in the bacterial cell.
AB  - Using a chromatographic method for the isolation and detection of periplasmic and
      cytoplasmic muropeptides avoiding radioactive labeling, we found that in the ampD
      negative strain JRG582 the anhydromuropeptide N-acetylmuramyl-L-alanyl-D
      glutamylmesodiaminopimelic acid (anhMurNAc tripeptide) accumulates not only in
      the cytoplasm but also in the periplasm. Simultaneously JRG582 carrying the
      Enterobacter cloacae genes ampC and ampR, which are necessary for the induction
      of beta-lactamase expression, overproduces beta-lactamase. We confirmed that the
      transmembrane protein AmpG transports a precursor muropeptide into the cytoplasm
      and that the formation of the anhMurNAc tripeptide takes place in the cytoplasm.
      anhMurNAc tripeptide can then be secreted into the periplasm. Therefore, the
      amount of anhMurNAc tripeptide in the cytoplasm is reduced not only by AmpD but
      also by transport out of the cell.

PMID- 8878602
TI  - Effect of fluconazole on fungicidal activity of flucytosine in murine
      cryptococcal meningitis.
AB  - Both animal and in vitro studies have demonstrated that combinations of
      flucytosine with amphotericin B and with fluconazole have significantly improved
      activity against cryptococcal meningitis compared with the activity of each drug
      used alone. However, very few dose levels of these agents have been tested in
      combination. This study evaluated the efficacy of fluconazole plus flucytosine in
      a murine model of cryptococcal meningitis over a broad range of dose combinations
      (fluconazole, 0 to 40 micrograms/g of body weight per day; flucytosine, 0 to 200
      micrograms/g/day). Both drugs were dissolved in drinking water, with treatment on
      days 2 to 11. In this highly reproducible model, fluconazole had a dramatic
      effect on the fungicidal activity of flucytosine. Flucytosine at dose levels of
      as much as 200 micrograms/g/day alone or in combination with low doses of
      fluconazole had minimal fungicidal activity, whereas in combination with
      fluconazole at 24 to 40 micrograms/g/day, flucytosine showed fungicidal activity
      in the range of 45 to 65% of the animals treated at doses of 40 to 100
      micrograms/g/day. This striking effect of fluconazole is consistent with the
      results of both in vitro and clinical studies. In the clinic, the use of
      flucytosine is often limited by severe toxicity, while toxicity is rarely
      observed with fluconazole. These results suggest that when flucytosine is given
      with higher doses of fluconazole, the maximum therapeutic effect of the former in
      the clinic may be observed at dose levels that are far less than the doses
      commonly employed (150 micrograms/g daily).

PMID- 8878603
TI  - Evidence that high-dosage zidovudine at time of retrovirus exposure reduces
      antiviral efficacy.
AB  - The antiviral efficacy of prophylactic 3'-azido-3'-deoxythymidine (AZT) therapy
      administered by continuous infusion or intermittent injection was compared in
      pediatric cats infected with feline leukemia virus. A 4-week treatment regimen of
      AZT was initiated at -48, 8, or 96 h postinfection (p.i.). For AZT therapy begun
      at -48 h p.i., significant efficacy was attained when therapy was given by
      continuous infusion but not by intermittent injection. However, when AZT therapy
      was delayed until 96 h p.i., both continuous infusion and intermittent injection
      gave complete protection. The results suggest that intermittent AZT
      administration is less efficacious than continuous infusion. Higher peak AZT
      concentrations in plasma associated with intermittent injection compared with
      those associated with continuous infusion may be immunotoxic, thus reducing the
      drug-induced vaccine effect. Furthermore, AZT toxicity seemed to be restricted to
      a window of sensitivity close to the time of virus challenge because delaying the
      start of AZT therapy until 96 h p.i. was highly efficacious, regardless of the
      method of administration.

PMID- 8878604
TI  - katG mutations in isoniazid-resistant Mycobacterium tuberculosis isolates
      recovered from Finnish patients.
AB  - katG and inhA genes from isoniazid-resistant Mycobacterium tuberculosis strains
      isolated in Finland were examined by PCR or sequencing. By PCR, katG was not
      detected in 3 of 54 strains. Sequencing of katG from 13 strains showed small
      point mutations or insertions; a previously described mutation causing a Ser-to
      Thr change at position 315 was found in 4 strains, and there were nine new
      missense mutations of katG. A 209-bp segment of inhA from 17 strains was
      sequenced, but no mutations were observed. This result indicates that different
      mutations prevail in different geographical areas.

PMID- 8878605
TI  - Canadian national survey of prevalence of antimicrobial resistance among clinical
      isolates of Streptococcus pneumoniae. Canadian Bacterial Surveillance Network.
AB  - The antimicrobial susceptibilities of 1,089 clinical isolates of Streptococcus
      pneumoniae obtained from 39 laboratories across Canada between October 1994 and
      August 1995 were determined. A total of 91 isolates (8.4%) demonstrated
      intermediate resistance (MIC, 0.1 to 1.0 microgram/ml) and 36 (3.3%) had high
      level resistance (MIC, > or = 2.0 micrograms/ml) to penicillin. Penicillin
      resistant strains were more likely to have been recovered from normally sterile
      sites (P = 0.005) and to be cross-resistant to several beta-lactam and non-beta
      lactam antimicrobial agents (P < 0.05). These results indicate that there has
      been a recent significant increase in the prevalence of antibiotic-resistant S.
      pneumoniae in Canada.

PMID- 8878606
TI  - Semisynthetic glycopeptide antibiotics derived from LY264826 active against
      vancomycin-resistant enterococci.
AB  - Certain derivatives of the glycopeptide antibiotic LY264826 with N-alkyl-linked
      substitutions on the epivancosamine sugar are active against glycopeptide
      resistant enterococci. Six compounds representing our most active series were
      evaluated for activity against antibiotic-resistant, gram-positive pathogens. For
      Enterococcus faecium and E. faecalis resistant to both vancomycin and
      teicoplanin, the MICs of the six semisynthetic compounds for 90% of the strains
      tested were 1 to 4 micrograms/ml, compared with 2,048 micrograms/ml for
      vancomycin and 256 micrograms/ml for LY264826. For E. faecium and E. faecalis
      resistant to vancomycin but not teicoplanin, the MICs were 0.016 to 1
      micrograms/ml, compared with 64 to 1,024 micrograms/ml for vancomycin. The
      compounds were highly active against vancomycin-susceptible enterococci and
      against E. gallinarum and E. casseliflavus and showed some activity against
      isolates of highly vancomycin-resistant leuconostocs and pediococci. The MICs for
      90% of the strains of methicillin-resistant Staphylococcus aureus tested were
      typically 0.25 to 1 micrograms/ml, compared with 1 microgram/ml for vancomycin.
      Against methicillin-resistant S. epidermidis MICs ranged from 0.25 to 2
      micrograms/ml, compared with 1 to 4 micrograms/ml for vancomycin and 4 to 16
      micrograms/ml for teicoplanin. The spectrum of these new compounds included
      activity against teicoplanin-resistant, coagulase-negative staphylococci. The
      compounds exhibited exceptional potency against pathogenic streptococci, with
      MICs of < or = 0.008 microgram/ml against Streptococcus pneumoniae, including
      penicillin-resistant isolates. In in vivo studies with a mouse infection model,
      the median effective doses against a challenge by S. aureus, S. pneumoniae, or S.
      pyogenes were typically 4 to 20 times lower than those of vancomycin. Overall,
      these new glycopeptides, such as LY307599 and LY333328, show promise for use as
      agents against resistant enterococci, methicillin-resistant S. aureus, and
      penicillin-resistant pneumococci.

PMID- 8878607
TI  - 3-day course of ofloxacin versus cefalexin in the treatment of urinary tract
      infections in postmenopausal women.

PMID- 8878609
TI  - Use of Mono Mac 6 human monocytic cell line and J774 murine macrophage cell line
      in parallel antimycobacterial drug studies.
AB  - The Mono Mac 6 (MM6) human monocytic cell line was evaluated with the established
      J774 murine macrophage cell line to ascertain its effectiveness in determining
      the intracellular activities of antimycobacterial drugs. Cells were infected with
      Mycobacterium tuberculosis H37Ra and treated with drug concentrations
      corresponding to the MICs, as well as to threefold higher than and threefold less
      than the MICs. Changes in CFU were compared after 7 days to determine significant
      differences between treated and nontreated groups. The results suggest that MM6
      will make a useful model for testing the intracellular activities of
      antituberculosis drugs.

PMID- 8878608
TI  - Population pharmacokinetics of ganciclovir in newborns with congenital
      cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.
AB  - The population pharmacokinetics of ganciclovir was investigated in a group of 27
      newborns with symptomatic congenital cytomegalovirus infection by nonlinear mixed
      effects modeling analysis. Individual characteristics including approximated
      creatinine clearance from serum (ASCC) and body weight (WGE) were identified to
      significantly influence total clearance from plasma (CL) and the apparent total
      volume of distribution (V) of ganciclovir, respectively. The regression equations
      used to model these relationships were expressed as CL (in liters per hour) =
      0.262 + (0.00271 x ASCC) and V (in liters) = 0.627 + (0.437 x WGE). By using this
      model, typical values of the pharmacokinetic parameter CL and V were 0.428 +/-
      0.079 liters/h and 1.773 +/- 0.320 liters, respectively. Upon validation with a
      larger number of newborns, this model should allow for the definition of possible
      relationships between the pharmacokinetic disposition of ganciclovir and
      pharmacodynamic events in neonates.

PMID- 8878610
TI  - Once-daily aminoglycoside therapy: potential ototoxicity.
AB  - Current data indicate that once-daily aminoglycoside therapy is as efficacious as
      traditional multiple daily dosing and equally or less toxic. Our experience with
      once-daily gentamicin, 6 mg/kg of body weight led to a 10% (3 of 33 patients)
      occurrence of documented ototoxicity after prolonged aminoglycoside exposure.

PMID- 8878611
TI  - Novel mutation (K70E) in human immunodeficiency virus type 1 reverse
      transcriptase confers decreased susceptibility to 9-[2
      (phosphonomethoxy)ethyl]adenine in vitro.
AB  - 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), an acyclic nucleoside phosphonate
      analog, is active against several retroviruses and herpesviruses and has shown
      anti-human immunodeficiency virus (HIV) activity in clinical trials. Serial
      passage of HIV type 1 (strain IIIb, in MT2 cells in increasing concentrations of
      PMEA resulted in viruses with > 12-fold increases in their 50% inhibitory
      concentrations of PMEA compared with that for strain IIIb. Sequence analyses of
      these PMEA-selected viruses demonstrated the presence of a novel lysine-to
      glutamic acid mutation at amino acid 70 (K70E) in HIV reverse transcriptase. A
      recombinant virus carrying the K70E mutation was constructed and showed a 10-fold
      increase in its 50% inhibitory concentrations of PMEA and 2',3'-dideoxy-3'
      thiacytidine but showed wild-type susceptibility levels to 2',3'-dideoxycytosine,
      2',3'-dideoxyinosine,2',3'-didehydro-2'3'-dideoxythymidine, 3'-azido-3'
      deoxythymidine, foscarnet, and two additional phosphonates, 9-[(R)-2
      (phosphonomethoxy)propyl]adenine and 9-[2,5-dihydro-5-(phosphonomethoxy)-2
      furanyl]adenine. Additionally, the K70E recombinant showed a minor reduction in
      growth kinetics compared with those of the wild-type virus in vitro.

PMID- 8878612
TI  - Systemic availability of itraconazole in lung transplantation.
AB  - Systemic availability of itraconazole in lung transplantation was evaluated by
      serially measuring the bioactivity of itraconazole in lung transplant patients
      who received itraconazole for prophylaxis (n = 12) or therapy (n = 5). These
      patients also received concomitant antacid and H2 blocker therapy. In patients
      receiving itraconazole at 200 and 400 mg/day, the median concentrations in serum
      were 0.5 microgram/ml (range, < 0.05 to 2.7) and 3.5 micrograms/ml (< 0.5 to 14),
      respectively. The concentration following administration of 400 mg/day was > 2.5
      micrograms/ml in 56% of samples, while only 4% of samples from patients who were
      administered 200 mg/day had levels over 2.5 micrograms/ml. This study documents
      that itraconazole can be absorbed in patients receiving concomitant antacid and
      H2 blocker therapy. However, the reduced and variable absorption suggests the
      importance of confirming drug delivery by measurement of concentrations in serum.

PMID- 8878613
TI  - Effects of cyclophosphamide and ceftriaxone on gastrointestinal colonization of
      mice by Candida albicans.
AB  - Adult male Crl:CD1 (ICR) mice were fed chow containing Candida albicans to induce
      sustained gastrointestinal colonization by the yeast. Groups of mice were
      rendered neutropenic with cyclophosphamide and subsequently received ceftriaxone,
      while other groups received normal saline and served as controls. Stool cultures
      were obtained immediately before and at the end of treatment. The administration
      of cyclophosphamide substantially increased the C. albicans counts in the stools
      of mice. The addition of ceftriaxone to the cyclophosphamide regimen did not
      significantly increase the level of gastrointestinal colonization by C. albicans.
      There was no evidence of Candida dissemination to internal organs.

PMID- 8878614
TI  - Macrolide-lincosamide-streptogramin B resistance in Staphylococcus lentus results
      from the integration of part of a transposon into a small plasmid.
AB  - The 8.0-kb macrolide-lincosamide-streptogramin B resistance plasmid pSES20 from
      Staphylococcus lentus harbored part of a Tn917-like transposon including the left
      terminal repeat, a gene almost identical to ermB, and its regulatory region, as
      well as the internal direct repeat. Homology between pSES20 and Tn917 ended at a
      sequence closely related to those of the resolution sites of Tn917 and Tn552 and
      staphylococcal recombination sites.

PMID- 8878615
TI  - Glycylcyclines bind to the high-affinity tetracycline ribosomal binding site and
      evade Tet(M)- and Tet(O)-mediated ribosomal protection.
AB  - N,N-dimethylglycylamido (DMG) derivatives of 6-demethyl-6-deoxytetracycline and
      doxycycline bind 5-fold more effectively than tetracycline to the tetracycline
      high-affinity binding site on the Escherichia coli 70S ribosome, which correlates
      with a 10-fold increase in potency for inhibition of E. coli cell-free
      translation. The potencies of DMG-doxycycline and DMG-6-demethyl-6
      deoxytetracycline were unaffected by the ribosomal tetracycline resistance
      factors Tet(M) and Tet(O) in cell-free translation assays and whole-cell
      bioassays with a conditional Tet(M)-producing E. coli strain.

PMID- 8878616
TI  - In vitro activity of BMS-181184 compared with those of fluconazole and
      amphotericin B against various candida spp.
AB  - We compared the in vitro activity of BMS-181184, the first compound of a new
      class of antifungal agents, the pradimicins, with those of fluconazole and
      amphotericin B against 64 clinical isolates of Candida species. MICs were
      determined by a microdilution method with high resolution medium for BMS-181184
      and fluconazole and antibiotic medium no. 3 with 2% glucose for amphotericin B.
      MICs of BMS-181184 for all yeasts were in the range of 0.78 to 12.5
      micrograms/ml. BMS-181184 was active against isolates resistant to other
      antifungal agents, consistent with a novel mode of action. Minimum fungicidal
      concentrations for 16 isolates showed that BMS-181184 was fungicidal. Clinical
      studies are now required to confirm its activity.

PMID- 8878618
TI  - Progress in molecular cytogenetics.

PMID- 8878617
TI  - In vitro activities of trovafloxacin against 557 strains of anaerobic bacteria.
AB  - The antimicrobial activity of trovafloxacin for 557 strains of anaerobic bacteria
      was determined by the National Committee for Clinical Laboratory Standards
      approved Wadsworth agar dilution technique. The species tested included
      Bacteroides fragilis (n = 91), other members of the B. fragilis group (n = 130),
      Campylobacter gracilis (n = 15), other Bacteroides spp. (n = 16), Prevotella spp.
      (n = 49), Porphyromonas spp. (n = 15), Fusobacterium spp. (n = 62), Bilophila
      wadsworthia (n = 24), Sutterella wadsworthensis (n = 21), Clostridium spp. (n =
      61), Peptostreptococcus spp. (n = 38), and gram-positive non-spore-forming rods
      (n = 35). Trovafloxacin inhibited all strains of B. fragilis at < or = 0.5
      microgram/ml, 99% of other B. fragilis group species at < or = 2 micrograms/ml,
      and 96% of all anaerobes tested at < or = 2 micrograms/ml.

PMID- 8878619
TI  - Localization of calcitonin mRNA using in situ labeling with reverse transcriptase
      and PCR.

PMID- 8878620
TI  - Demonstration of calcitonin mRNA in rat thyroid C-cells and endocrine cells of
      the lung: comparison of immunocytochemical and hybridocytochemical results.

PMID- 8878621
TI  - Participation of 125 kDa tyrosine-phosphorylated protein in phagocytosis of
      Acanthamoeba cells.

PMID- 8878622
TI  - Markham rotation of the electron microscopic images of cilia as an accessory
      method in differential diagnosis between Kartagener syndrome and Sturgess
      syndrome.

PMID- 8878623
TI  - Nuclear bodies in hepatocytes of the rat.

PMID- 8878624
TI  - Ultrastructural changes in acinar cell mitochondria of the rat pancreas in the
      course of lead intoxication.

PMID- 8878625
TI  - The secretory compartment of exocrine pancreas in taurocholate pancreatitis in
      rats. Ultrastructural and biochemical aspects.

PMID- 8878626
TI  - Ultrastructural evaluation of Morris hepatoma metastases to the lungs after local
      administration of Mutein VI hrecTNF-alpha.

PMID- 8878627
TI  - Ultrastructural evaluation of adenomyotic and endometrial tissue glands of women
      in the proliferative phase of the menstrual cycle.

PMID- 8878628
TI  - Role of oxygen free radicals in cardiocyte injury in the reperfused rat heart.

PMID- 8878629
TI  - Type II alveolar epithelial cells promote fibrosis during development of
      experimental lung emphysema.

PMID- 8878630
TI  - Comparative ultrastructural morphometric analysis of satellite cells in three rat
      muscles: latissimus dorsi, gastrocnemius and quadriceps.

PMID- 8878631
TI  - Morphometric ultrastructural analysis of germ cells of fetal male mouse gonads.

PMID- 8878632
TI  - Morphometric analysis of argyrophilia.

PMID- 8878633
TI  - Usefulness of nucleolar organiser region staining (AgNORs) in the evaluation of
      follicular tumours of the thyroid.

PMID- 8878634
TI  - Ultrastructural components of the nuclei of undifferentiated crypt base cells in
      the human small intestine-stereological estimation of volumes.

PMID- 8878635
TI  - Apoptosis of WEHI-3B cells after Maphosphamide treatment.

PMID- 8878636
TI  - The use of flow cytometry for the investigation of viability of heart valve
      derived fibroblasts.

PMID- 8878637
TI  - Physical restraints in applying image analysis to quantitative studies.

PMID- 8878638
TI  - Dose-dependent effects of Cd2+, Co2+, Ni2+ and La3+ on guinea pig peritoneal
      exudate neutrophil (heterophil) granulocytes in vitro.

PMID- 8878639
TI  - Comparative studies on mast cell distribution in the skin of humans and
      laboratory animals. A preliminary report.

PMID- 8878640
TI  - Modyfying effect of quercetin on the lipid membrane.

PMID- 8878641
TI  - The ultrastructure of lymphatic vessels emanating from the uterus and forming
      subovarian lymphatic plexus in pigs.

PMID- 8878642
TI  - Ultrastructural changes in mesometrial lymphatics during the oestrous cycle in
      pigs.

PMID- 8878643
TI  - NADPH-diaphorase histochemistry in the endothelial cells of lymph vessels in the
      broad ligament of the uterus of ovariectomized pigs.

PMID- 8878644
TI  - The influence of estradiol on the activity of NADPH-diaphorase in the endothelium
      of the blood vessels in the broad ligament of the uterus of ovariectomized pigs.

PMID- 8878645
TI  - Morphology of human brain stem venous vessels in fetal period.

PMID- 8878646
TI  - Characteristics of human tentorial sinus.

PMID- 8878647
TI  - Chances of using splenic artery as an accessory source of blood supply for
      kidneys.

PMID- 8878648
TI  - Effect of co-culture with thyroid follicular cells on expression of calcitonin
      gene in parafollicular TT cells.

PMID- 8878649
TI  - Immunocytochemical localization of hormones and functional proteins in cultured
      cells of thyroid medullary carcinoma.

PMID- 8878650
TI  - The effect of steroids and their complexes with cyclodextrins on secretory
      activity of cultured thyroid medullary carcinoma cells.

PMID- 8878651
TI  - Morphochemical investigations on postnatal development of the adrenal medulla in
      guinea pigs.

PMID- 8878652
TI  - Morphobiochemical investigations of the thyroid glands of guinea pigs after the
      application of exogenous histamine.

PMID- 8878653
TI  - Application of the cell and molecular biology techniques in evaluation of the
      local mechanisms controlling spermatogenesis.

PMID- 8878654
TI  - Opioids as regulators of local function in the testis.

PMID- 8878655
TI  - Basal and LH stimulated testosterone secretion by rat Leydig cells in primary
      culture under an influence of serotonin.

PMID- 8878656
TI  - An in vivo and in vitro study on the role of macrophages in local regulation of
      the Leydig cell function in the rat.

PMID- 8878657
TI  - Evaluation of human spermatozoa using video imaging technique and flow cytometry.

PMID- 8878658
TI  - Rat epididymal epithelial cells produce nitric oxide upon concomitant
      lipopolysaccharide and interferon-gamma stimulation.

PMID- 8878659
TI  - Morphological indications of the functional maturation of the nervous system.

PMID- 8878660
TI  - Ultrastructural study on axonal and dendritic growth cones in the human embryonic
      spinal cord.

PMID- 8878661
TI  - Galanin, substance P and calcitonin gene-related peptide are colocalized in some
      afferent neurons innervating the porcine ovary.

PMID- 8878662
TI  - Adrenergic innervation of the ovarian cortical structures in the sexual cycle of
      the white rat.

PMID- 8878663
TI  - Binding of anti-immunoglobulin antibodies to the fibrous connective tissue of
      skeletal muscle.

PMID- 8878664
TI  - Histochemical and biochemical investigations on the guinea pig parotid glands
      after application of exogenous histamine.

PMID- 8878665
TI  - Effect of vanadium on rat erythrocytes in vitro.

PMID- 8878666
TI  - Local reaction from eosinophils in the development of Morris hepatoma after
      hrecTNF-alpha administration.

PMID- 8878667
TI  - Myoepithelial cell and its function.

PMID- 8878668
TI  - Recollections of Howard Temin (1934-1994).

PMID- 8878669
TI  - Destabilization of bacteriophage T4 mRNAs by a mutation of gene 61.5.
AB  - We identified a novel gene of bacteriophage T4, gene 61.5, which appears to be
      involved in protein synthesis late in infection. Northern blot analysis revealed
      that a mutant of 61.5 accumulated truncated transcripts of representative late
      genes. Using a double mutant of genes 61.5 and 55, which prevents transcription
      of late genes, we demonstrate that even transcripts of middle genes, while full
      length when initially expressed, are similarly truncated at later stages of
      infection. These results indicate that the abnormality in transcript length
      occurs late in infection, regardless of whether the transcript derives from a
      middle or a late gene. Primer-extension analysis revealed that the 5' ends of the
      late gene 23 transcripts that accumulated in gene 61.5 mutant-infected cells were
      located at internal discrete sites as well as at the expected transcription start
      site. Moreover, the decay rates of full-length transcripts from genes uvsY or 45
      were more than twofold faster in the absence of a functional gene 61.5. These
      results suggest that mutation of gene 61.5 activates endonucleolytic cleavage of
      middle and late transcripts, probably by RNase M.

PMID- 8878670
TI  - DNA adenine methylase mutants of Salmonella typhimurium and a novel dam-regulated
      locus.
AB  - Mutants of Salmonella typhimurium lacking DNA adenine methylase were isolated;
      they include insertion and deletion alleles. The dam locus maps at 75 min between
      cysG and aroB, similar to the Escherichia coli dam gene. Dam- mutants of S.
      typhimurium resemble those of E coli in the following phenotypes: (1) increased
      spontaneous mutations, (2) moderate SOS induction, (3) enhancement of duplication
      segregation, (4) inviability of dam recA and dam recB mutants, and (5)
      suppression of the inviability of the dam recA and dam recB combinations by
      mutations that eliminate mismatch repair. However, differences between S.
      typhimurium and E. coli dam mutants are also found: (1) S. typhimurium dam
      mutants do not show increased UV sensitivity, suggesting that methyl-directed
      mismatch repair does not participate in the repair of UV-induced DNA damage in
      Salmonella. (2) S. typhimurium dam recJ mutants are viable, suggesting that the
      Salmonella RecJ function does not participate in the repair of DNA strand breaks
      formed in the absence of Dam methylation. We also describe a genetic screen for
      detecting novel genes regulated by Dam methylation and a locus repressed by Dam
      methylation in the S. typhimurium virulence (or "cryptic") plasmid.

PMID- 8878672
TI  - The efficiency of meiotic recombination between dispersed sequences in
      Saccharomyces cerevisiae depends upon their chromosomal location.
AB  - To examine constrains imposed on meiotic recombination by homologue pairing, we
      measured the frequency of recombination between mutant alleles of the ARG4 gene
      contained in pBR322-based inserts. Inserts were located at identical loci on
      homologues (allelic recombination) or at different loci on either homologous or
      heterologous chromosomes (ectopic recombination). Ectopic recombination between
      interstitially located inserts on heterologous chromosomes had an efficiency of 6
      12% compared to allelic recombination. By contrast, ectopic recombination between
      interstitial inserts located on homologues had relative efficiencies of 47-99%.
      These findings suggest that when meiotic ectopic recombination occurs, homologous
      chromosomes are already colocalized. The efficiency of ectopic recombination
      between inserts on homologues decreased as the physical distance between insert
      sites was increased. This result is consistent with the suggestion that during
      meiotic recombination, homologues are not only close to each other, but also are
      aligned end to end. Finally, the efficiency of ectopic recombination between
      inserts near telomeres (within 16 kb) was significantly greater than that
      observed with inserts > 50 kb from the nearest telomere. Thus, at the time of
      recombination, there may be a special relationship between the ends of
      chromosomes not shared with interstitial regions.

PMID- 8878671
TI  - A test of the double-strand break repair model for meiotic recombination in
      Saccharomyces cerevisiae.
AB  - We tested predictions of the double-strand break repair (DSBR) model for meiotic
      recombination by examining the segregation patterns of small palindromic
      insertions, which frequently escape mismatch repair when in heteroduplex DNA. The
      palindromes flanked a well characterized DSB site at the ARG4 locus. The
      "canonical" DSBR model, in which only 5' ends are degraded and resolution of the
      four-stranded intermediate is by Holliday junction resolvase, predicts that hDNA
      will frequently occur on both participating chromatids in a single event. Tetrads
      reflecting this configuration of hDNA were rare. In addition, a class of tetrads
      not predicted by the canonical DSBR model was identified. This class represented
      events that produced hDNA in a "trans" configuration, on opposite strands of the
      same duplex on the two sides of the DSB site. Whereas most classes of convertant
      tetrads had typical frequencies of associated crossovers, tetrads with trans hDNA
      were parental for flanking markers. Modified versions of the DSBR model,
      including one that uses a topoisomerase to resolve the canonical DSBR
      intermediate, are supported by these data.

PMID- 8878673
TI  - Mutants of Saccharomyces cerevisiae with defects in acetate metabolism: isolation
      and characterization of Acn- mutants.
AB  - The two carbon compounds, ethanol and acetate, can be oxidatively metabolized as
      well as assimilated into carbohydrate in the yeast Saccharomyces cerevisiae. The
      distribution of acetate metabolic enzymes among several cellular compartments,
      mitochondria, peroxisomes, and cytoplasm makes it an intriguing system to study
      complex metabolic interactions. To investigate the complex process of carbon
      catabolism and assimilation, mutants unable to grow on acetate were isolated. One
      hundred five Acn- ("ACetate Nonutilizing") mutants were sorted into 21
      complementation groups with an additional 20 single mutants. Five of the groups
      have defects in TCA cycle enzymes: MDH1, CIT1, ACO1, IDH1, and IDH2. A defect in
      RTG2, involved in the retrograde communication between the mitochondrion and the
      nucleus, was also identified. Four genes encode enzymes of the glyoxylate cycle
      and gluconeogenesis: ICL1, MLS1, MDH2, and PCK1. Five other genes appear to be
      defective in regulating metabolic activity since elevated levels of enzymes in
      several metabolic pathways, including the glyoxylate cycle, gluconeogenesis, and
      acetyl-CoA metabolism, were detected in these mutants: ACN8, ACN9, ACN17, ACN18,
      and ACN42. In summary, this analysis has identified at least 22 and as many as 41
      different genes involved in acetate metabolism.

PMID- 8878674
TI  - Analysis of meiotic recombination pathways in the yeast Saccharomyces cerevisiae.
AB  - In the yeast, Saccharomyces cerevisiae, several genes appear to act early in
      meiotic recombination. HOP1 and RED1 have been classified as such early genes.
      The data in this paper demonstrate that neither a red nor a hop1 mutation can
      rescue the inviable spores produced by a rad52 spo13 strain; this phenotype helps
      to distinguish these two genes from other early meiotic recombination genes such
      as SPO11, REC104, or MEI4. In contrast, either a red1 or a hop1 mutation can
      rescue a rad50S spo13 strain; this phenotype is similar to that conferred by
      mutations in the other early recombination genes (e.g., REC104). These two
      different results can be explained because the data presented here indicate that
      a rad50S mutation does not diminish meiotic intrachromosomal recombination,
      similar to the mutant phenotypes conferred by red1 or hop1. Of course, RED1 and
      HOP1 do act in the normal meiotic interchromosomal recombination pathway; they
      reduce interchromosomal recombination to approximately 10% of normal levels. We
      demonstrate that a mutation in a gene (REC104) required for initiation of
      exchange is completely epistatic to a mutation in RED1. Finally, mutations in
      either HOP1 or RED1 reduce the number of double-strand breaks observed at the
      HIS2 meiotic recombination hotspot.

PMID- 8878675
TI  - Multiple versions of the A mating type locus of Coprinus cinereus are generated
      by three paralogous pairs of multiallelic homeobox genes.
AB  - The A mating type locus of Coprinus cinereus determines mating compatibility by
      regulating essential steps in sexual development. Each A locus contains several
      genes separated into two functionally independent complexes termed A alpha and A
      beta, and the multiple alleles of these genes generate an estimated 160 A mating
      specificities. The genes encode two classes of homeodomain-containing proteins
      designated HD1 and HD2. In this report we describe two newly cloned loci, A2 and
      A5, and compare them with A42, A43 and A6 that we have described previously. An A
      beta-null locus, retaining just a single active HD1 gene from the alpha-complex,
      was generated by mutation. Using this as a transformation host, gene combinations
      that promote A-regulated development were identified. We demonstrate that each A
      locus contains members of three paralogous pairs of HD1 and HD2 genes. Different
      allelic versions of gene pairs are compatible but paralogous genes are
      incompatible. The genes present in four uncloned A loci were deduced using
      Southern analyses and transformations with available cloned genes. The combined
      analysis of nine A factors identifies sufficient A gene alleles to generate at
      least 72 A mating specificities.

PMID- 8878677
TI  - Specificity of chromosome damage caused by the Rex element of Drosophila
      melanogaster.
AB  - Rex is a multicopy genetic element that maps within an X-linked ribosomal RNA
      gene (rDNA) array of D. melanogaster. Acting maternally, Rex causes recombination
      between rDNA arrays in a few percent of early embryos. With target chromosomes
      that contain two rDNA arrays, the exchanges either delete all of the material
      between the two arrays or invert the entire intervening chromosomal segment.
      About a third of the embryos produced by Rex homozygotes have cytologically
      visible chromosome damage, nearly always involving a single chromosome. Most of
      these embryos die during early development, displaying a characteristic apoptosis
      like phenotype. An experiment that tests whether the cytologically visible damage
      is rDNA-specific is reported here. In this experiment, females heterozygous for
      Rex and an rDNA-deficient X chromosome were crossed to males of two genotypes.
      Some of the progeny from the experimental cross entirely lacked rDNA, while all
      of the progeny from the control cross had at least one rDNA array. A
      significantly lower frequency of early-lethal embryos in the experimental cross,
      proportionate to the fraction of rDNA-deficient embryos, demonstrates that Rex
      preferentially damages rDNA.

PMID- 8878676
TI  - Both loss-of-function and gain-of-function mutations in snf define a role for
      snRNP proteins in regulating Sex-lethal pre-mRNA splicing in Drosophila
      development.
AB  - The Drosophila snf gene encodes a protein with functional homology to the
      mammalian U1A and U2B" snRNP proteins. Studies, based on the analysis of three
      viable alleles, have suggested a role for snf in establishing the female-specific
      splicing pattern of the sex determination switch gene, sex-lethal. Here, we show
      that the non-sex-specific lethal null allele is required for female sex
      determination, arguing against the formal possibility that the viable alleles
      disrupt a function unrelated to snf's wild-type function. Moreover, we find snf
      is required for normal cell growth and/or survival, as expected for a protein
      involved in a cell-vital process such as RNA splicing. We also show that of the
      three viable alleles only one, snfJA2, is a partial loss-of-function mutation.
      The other two viable alleles, snf1621 and snfe8H, encode antimorphic proteins. We
      find the antimorphic proteins are mislocalized and correlate their
      mislocalization with their molecular lesions and mutant phenotypes. Finally, we
      provide genetic evidence that the antimorphic alleles interfere with the
      autoregulatory splicing function of the Sex-lethal protein. Based on these
      studies we suggest a model in which the snRNP protein, Snf, functions with Sex
      lethal to block recognition of the regulated male-specific exon.

PMID- 8878678
TI  - The heterochromatic rolled gene of Drosophila melanogaster is extensively
      polytenized and transcriptionally active in the salivary gland chromocenter.
AB  - This paper reports a cytogenetic and molecular study of the structural and
      functional organization of the Drosophila melanogaster chromocenter. The
      relations between mitotic (constitutive) heterochromatin and alpha- and beta
      heterochromatin are not fully understood. In the present work, we have studied
      the polytenization of the rolled (rl) locus, a 100-kb genomic region that maps to
      the proximal heterochromatin of chromosome 2 and has been previously thought to
      contribute to alpha-heterochromatin. We show that rolled undergoes polytenization
      in salivary gland chromosomes to a degree comparable to that of euchromatic
      genes, despite its deep heterochromatic location. In contrast, both the Bari-1
      sequences and the AAGAC satellite repeats, located respectively the left and
      right of rl, are severely underrepresented and thus both appear to be alpha
      heterochromatic. In addition, we found that rl is transcribed in polytene
      tissues. Together, the results reported here indicate that functional sequences
      located within the proximal constitutive heterochromatin can undergo
      polytenization, contributing to the formation of beta-heterochromatin. The
      implications of this finding to chromocenter structure are discussed.

PMID- 8878679
TI  - rdgE: a novel retinal degeneration mutation in Drosophila melanogaster.
AB  - We report isolating the Drosophila retinal degeneration E (rdgE) mutation. The
      hypomorphic rdgE1 allele causes rapid photoreceptor degeneration in light and a
      slower rate of degeneration when the flies are raised in constant darkness. The
      rdgE1 flies exhibited an electrophysiological light response that decreased with
      age, coinciding with the degeneration. This suggests that degeneration caused the
      loss of the light response. We determined that the ninaE (rhodopsin) mutation,
      but not norpA [phospholipase C (PLC)], slowed the rdgE-dependent degeneration.
      This was consistent with the light-enhanced degeneration, but revealed that the
      degeneration is independent of the PLC-mediated phototransduction cascade.
      Transmission electron microscopy revealed that rdgE1 photoreceptors exhibited a
      number of vesicular transport defects including unpacking/vesiculation of
      rhabdomeres, endocytosis of novel vesicles by photoreceptors, a buildup of very
      large multivesicular bodies, and an increased amount of rough endoplasmic
      reticulum. We determined that the rdgE null phenotype is a late embryonic
      lethality. Therefore, rdgE+ is required in cells outside of the retina, quite
      possibly in a large number of neurons. Thus, rdgE may define a mutational class
      that exhibits both light-enhanced retinal degeneration and a recessive null
      lethality by perturbing neuronal membrane biosynthesis and/or recycling.

PMID- 8878680
TI  - Differentiation of Muller's chromosomal elements D and E in the obscura group of
      Drosophila.
AB  - Twenty-two markers located on Muller's elements D or E have been mapped by in
      situ hybridization in six species of the obscura group of Drosophila and in D.
      melanogaster. The obscura species can be grouped into a Palearctic cluster (D.
      subobscura, D. madeirensis and D. guanche) and a Nearctic one (D. pseudoobscura,
      D. persimilis and D. miranda). Eleven of the probes contain known genes: E74,
      Acp70A, Est5, hsp28/23, hsp83, emc, hsp70, Xdh, Acph-1, Cec and rp49. The
      remaining probes are recombinant phages isolated from a D. subobscura genomic
      library. All these markers hybridize to the putative homologous chromosome or
      chromosomal arm of elements D and E. Thus, these elements have conserved their
      genic content during species divergence. Chromosomal homologies proposed
      previously for each element among the species of the same cluster have been
      compared with the present results. The distribution of markers within each
      element has changed considerably as inferred from pairwise comparisons of obscura
      species included in the two different clusters. Only chromosomal segments defined
      by closely linked markers have been conserved: one such segment has been detected
      in element D and three in element E between D subobscura and D. pseudoobscura.

PMID- 8878681
TI  - Duplicated proteasome subunit genes in Drosophila melanogaster encoding testes
      specific isoforms.
AB  - Using the previously cloned proteasome alpha-type subunit gene Pros28.1, we
      screened a Drosophila melanogaster genomic library using reduced stringency
      conditions to identify closely related genes. Two new genes, Pros28.1A (map
      position 92F) and Pros28.1B (map position 60D7), showing high sequence similarity
      to Pros28.1, were identified and characterized. Pros28.1A encodes a protein with
      74% amino acid identity to PROS28.1, while the Pros28.1B gene product is 58%
      identical. The Pros28.1B gene has two introns, located in exactly analogous
      positions as the two introns in Pros28.1, while the Pros28.1A gene lacks introns.
      Northern blot analysis reveals that the two new genes are expressed only in
      males, during the pupal and adult stages. Tissue-specific patterns of expression
      were examined using transgenic flies carrying lacz-fusion reporter genes. This
      analysis revealed that both genes are expressed in germline cells during
      spermatogenesis, although their expression patterns differed. Pros28.1A
      expression is first detected at the primary spermatocyte stage and persists into
      the spermatid elongation phase of spermiogenesis, while Pros28.1B expression is
      prominent only during spermatid elongation. These genes represent the most
      striking example of cell-type-specific proteasome gene expression reported to
      date in any system and support the notion that there is structural and functional
      heterogeneity among proteasomes in metazoans.

PMID- 8878682
TI  - The Drosophila Eip78C gene is not vital but has a role in regulating chromosome
      puffs.
AB  - We have generated a number of chromosomal aberrations that disrupt the early-late
      ecdysone-induced 78C puff gene (Eip78C, ecdysone-induced protein, FlyBase name
      for the E78 gene of Stone and Thummel 1993), which encodes the two members of the
      nuclear hormone receptor superfamily Eip78C-A and Eip78C-B. The aberrations
      include deletions of the ligand-binding/dimerization domain of both, inversions
      that split Eip78C-A but retain residual Eip78C-B expression, and a small deletion
      specific for Eip78C-B. We find that wild-type Eip78C functions are completely
      dispensable for normal development under laboratory conditions. However, we show
      that Eip78C-B is required for the maximal puffing activity of a subset of late
      puffs (63E and 82F) since these puffs are reduced in size in Eip78C-B mutant
      backgrounds. Paradoxically the same late puffs are reduced, as well as at least
      one other, when the Eip78C-B cDNA is overexpressed from a heat shock promoter.
      These data indicate either that Eip78C function is redundant or that it plays a
      subtle modulating role in the regulation of chromosome puffing.

PMID- 8878683
TI  - Comparison of the structure and expression of odd-skipped and two related genes
      that encode a new family of zinc finger proteins in Drosophila.
AB  - The odd-skipped (odd) gene, which was identified on the basis of a pair-rule
      segmentation phenotype in mutant embryos, is initially expressed in the
      Drosophila embryo in seven pair-rule stripes, but later exhibits a segment
      polarity-like pattern for which no phenotypic correlate is apparent. We have
      molecularly characterized two embryonically expressed odd-cognate genes, sob and
      bowel (bowl), that encode proteins with highly conserved C2H2 zinc fingers. While
      the Sob and Bowl proteins each contain five tandem fingers, the Odd protein lacks
      a fifth (C-terminal) finger and is also less conserved among the four common
      fingers. Reminiscent of many segmentation gene paralogues, the closely linked odd
      and sob genes are expressed during embryogenesis in similar striped patterns; in
      contrast, the less-tightly linked bowl gene is expressed in a distinctly
      different pattern at the termini of the early embryo. Although our results
      indicate that odd and sob are more likely than bowl to share overlapping
      developmental roles, some functional divergence between the Odd and Sob proteins
      is suggested by the absence of homology outside the zinc fingers, and also by
      amino acid substitutions in the Odd zinc fingers at positions that appear to be
      constrained in Sob and Bowl

PMID- 8878684
TI  - gutfeeling, a Drosophila gene encoding an antizyme-like protein, is required for
      late differentiation of neurons and muscles.
AB  - The gutfeeling (guf) gene was uncovered in a genetic screen for genes that are
      required for proper development of the embryonic peripheral nervous system.
      Mutations in guf cause defects in growth cone guidance and fasciculation and loss
      of expression of several neuronal markers in the embryonic peripheral and central
      nervous systems. guf is required for terminal differentiation of neuronal cells.
      Mutations in guf also affect the development of muscles in the embryo. In the
      absence or guf activity, myoblasts are formed properly, but myoblast fusion and
      further differentiation of muscle fibers is severely impaired. The guf gene was
      cloned and found to encode a 21-kD protein with a significant sequence similarity
      to the mammalian ornithine decarboxylase antizyme (OAZ). In mammals, OAZ plays a
      key regulatory role in the polyamine biosynthetic pathway through its binding to,
      and inhibition of, ornithine decarboxylase (ODC), the first enzyme in the
      pathway. The elaborate regulation of ODC activity in mammals still lacks a
      defined developmental role and little is known about the involvement of
      polyamines in cellular differentiation. GUF is the first antizyme-like protein
      identified in invertebrates. We discuss its possible developmental roles in light
      of this homology.

PMID- 8878685
TI  - Chromosomal distribution of transposable elements in Drosophila melanogaster:
      test of the ectopic recombination model for maintenance of insertion site number.
AB  - Data of insertion site localization and site occupancy frequency of P, hobo, I,
      copia, mdg1, mdg3, 412, 297, and roo transposable elements (TEs) on the polytene
      chromosomes of Drosophila melanogaster were extracted from the literature. We
      show that TE insertion site number per chromosomal division was significantly
      correlated with the amount of DNA. The insertion site number weighted by DNA
      content was not correlated with recombination rate for all TEs except hobo, for
      which a positive correlation was detected. No global tendency emerged in the
      relationship between TE site occupancy frequency, weighted by DNA content, and
      recombination rate; a strong negative correlation was, however, found for the 3L
      arm. A possible dominant deleterious effect of chromosomal rearrangements due to
      recombination between TE insertions is thus not the main factor explaining the
      dynamics of TEs, since this hypothesis implies a negative relationship between
      recombination rate and both TE insertion site number and site occupancy
      frequency. The alternative hypothesis of selection against deleterious effects of
      insertional mutations is discussed.

PMID- 8878686
TI  - Large genetic change at small fitness cost in large populations of Drosophila
      melanogaster selected for wind tunnel flight: rethinking fitness surfaces.
AB  - The fitness effects of extreme genetic change by selection were studied in large
      populations subjected to prolonged, intense selection. Two replicate populations
      of Drosophila melanogaster, with estimated effective sizes 500 < or = Ne < or =
      1000, were selected for increased performance in a wind tunnel, selecting on
      average the fastest 4.5% of flies. The mean apparent flying speed of both lines
      increased from approximately 2 to 170 cm/sec and continued to respond at
      diminishing rates, without reaching a plateau, for 100 generations. Competitive
      fitness tests in generations 50 and 85 showed minimal or no fitness loss in
      selected lines compared to controls. Sublines relaxed in generations 65 and 85
      showed minimal or no regression in apparent flying speed. Hybrid lines, from a
      cross of selected x control lines in generation 75, responded to reselection
      saltationally, showing that the chromosomes of the selected lines had been
      assembled from alleles at many loci, from many different chromosomes in the base
      population. Thus, major genetic change was achieved, but without the costs
      usually associated with strong directional selection. Large population size has
      been interpreted, in opposing models, as either a brake or an accelerator in its
      effects on long-term change by selection. These results favor the second model,
      and challenge the concept of rugged fitness surfaces underlying the first model.

PMID- 8878687
TI  - Cloning of the Drosophila melanogaster meiotic recombination gene mei-218: a
      genetic and molecular analysis of interval 15E.
AB  - The mei-218 gene product is required for both meiotic crossing over and for the
      production of recombination modules, suggesting that these organelles are
      required for meiotic exchange. In this study the null phenotype of mei-218 was
      defined through the analysis of three preexisting and five new alleles.
      Consistent with previous studies, in homozygous mei-218 mutants meiotic crossing
      over is reduced to < 10% of normal levels. A molecular analysis of mei-218 was
      initiated with the isolation and mapping of lethal mutations and genome
      rearrangements in the region containing mei-218, polytene interval 15E on the X
      chromosome. This high resolution genetic map was aligned with a physical map
      constructed from cosmid and P1 clones by genetically mapping restriction fragment
      length polymorphisms and localizing rearrangement breakpoints. Within a region of
      65 kb, we have identified seven transcription units, including mei-218 and the
      Minute(1)15D gene, which encodes ribosomal protein S5. The mei-218 mutant
      phenotype has been rescued by germline transformation with both a genomic
      fragment and a cDNA under the control of the hsp83 promoter. The mei-218 gene is
      predicted to produce an 1186-amino acid protein that has no significant
      similarities to any known proteins.

PMID- 8878688
TI  - Environmental and genetic effects on the asymmetry phenotype: Diazinon resistance
      in the Australian sheep blowfly, Lucilia cuprina.
AB  - The asymmetry phenotype of diazinon-resistant flies lacking a fitness/asymmetry
      Modifier (+/+; R/-) was dominant and independent of developmental temperature,
      larval density and diazinon concentration. Asymmetry score, pooled over three
      bristle characters, was approximately 50% greater for these phenotypes than for
      those of modified genotypes (M/+; +/+) and unmodified susceptibles (+/+; S/S)
      reared under standard laboratory conditions. Modified and susceptible phenotypes
      showed increased asymmetry score for temperatures and larval densities above and
      below standard rearing conditions; a positive correlation was observed between
      diazinon concentration and asymmetry score. Single and multiple environmental
      stresses resulted in similar scores that approached, but never exceeded, those of
      unmodified resistant phenotypes. Irrespective of the developmental conditions
      anti-symmetry and fluctuating asymmetry were typically observed for each bristle
      character of unmodified resistant and the modified and susceptible phenotypes,
      respectively. Thus while similar asymmetry scores could arise from genetic or
      environmental effects, asymmetry pattern was genetically based. Population cage
      analyses at different temperatures and larval densities showed a negative
      association between mean asymmetry and relative fitness.

PMID- 8878689
TI  - The effects of natural hybridization on the regulation of doubly uniparental
      mtDNA inheritance in blue mussels (Mytilus spp.).
AB  - Blue mussels in the Mytilus edulis species complex have a doubly uniparental mode
      of mtDNA inheritance with separate maternal and paternal mtDNA lineages. Female
      mussels inherit their mtDNA solely from their mother, while males inherit mtDNA
      from both parents. In the male gonad the paternal mtDNA is preferentially
      replicated so that only paternal mtDNA is transmitted from fathers to sons.
      Hybridization is common among differentiated blue mussel taxa; whenever it
      involves M. trossulus, doubly uniparental mtDNA inheritance is disrupted. We have
      found high frequencies of males without and females with paternal mtDNA among
      hybrid mussels produced by interspecific matings between M. galloprovincialis and
      M. trossulus. In contrast, hybridization between M. galloprovincialis and M.
      edulis does not affect doubly uniparental inheritance, indicating a difference in
      the divergence of the mechanisms regulating mtDNA inheritance among the three
      blue mussel taxa. Our data indicate a high frequency of disrupted mtDNA
      transmission in F1 hybrids and suggest that two separate mechanisms, one
      regulating the transmission of paternal mtDNA to males and another inhibiting the
      establishment of paternal mtDNA in females, act to regulate doubly uniparental
      inheritance. We propose a model for the regulation of doubly uniparental
      inheritance that is consistent with these observations.

PMID- 8878690
TI  - Evolution of mouse T-box genes by tandem duplication and cluster dispersion.
AB  - The T-box genes comprise an ancient family of putative transcription factors
      conserved across species as divergent as Mus musculus and Caenorhabditis elegans.
      All T-box gene products are characterized by a novel 174-186-amino acid DNA
      binding domain called the T-box that was first discovered in the polypeptide
      products of the mouse T locus and the Drosophila melanogaster optomotor-blind
      gene. Earlier studies allowed the identification of five mouse T-box genes, T,
      Tbx1-3, and Tbr1, that all map to different chromosomal locations and are
      expressed in unique temporal and spatial patterns during embryogenesis. Here, we
      report the discovery of three new members of the mouse T-box gene family, named
      Tbx4, Tbx5, and Tbx6. Two of these newly discovered genes, Tbx4 and Tbx5, were
      found to be tightly linked to previously identified T-box genes. Combined results
      from phylogenetic, linkage, and physical mapping studies provide a picture for
      the evolution of a T-box subfamily by unequal crossing over to form a two-gene
      cluster that was duplicated and dispersed to two chromosomal locations. This
      analysis suggests that Tbx4 and Tbx5 are cognate genes that diverged apart from a
      common ancestral gene during early vertebrate evolution.

PMID- 8878691
TI  - Coupled site-directed mutagenesis/transgenesis identifies important functional
      domains of the mouse agouti protein.
AB  - The agouti locus encodes a novel paracrine signaling molecule containing a signal
      sequence, an N-linked glycosylation site, a central lysine-rich basic domain, and
      a C-terminal tail containing 10 cysteine (Cys) residues capable of forming five
      disulfide bonds. When overexpressed, agouti causes a number of pleiotropic
      effects including yellow coat and adult-onset obesity. Numerous studies suggest
      that agouti causes yellow coat color by antagonizing the binding of alpha
      melanocyte-stimulating hormone (alpha-MSH) to the alpha-MSH-(Melanocortin-1)
      receptor. With the goal of identifying functional domains of agouti important for
      its diverse biological activities, we have generated 14 agouti mutations by in
      vitro site-directed mutagenesis and analyzed these mutations in transgenic mice
      for their effects on coat color and obesity. These studies demonstrate that the
      signal sequence, the N-linked glycosylation site, and the C-terminal Cys residues
      are important for full biological activity, while at least a portion of the
      lysine-rich basic domain is dispensable for normal function. They also show that
      the same functional domains of agouti important to coat color determination are
      important for inducing obesity, consistent with the hypothesis that agouti
      induces obesity by antagonizing melanocortin binding to other melanocortin
      receptors.

PMID- 8878692
TI  - Opposite orientations of an inverted duplication and allelic variation at the
      mouse agouti locus.
AB  - The mouse agouti protein is a paracrine signaling molecule that causes yellow
      pigment synthesis. A pale ventral coloration distinguishes the light-bellied
      agouti (AW) from the agouti (A) allele, and is caused by expression of ventral
      specific mRNA isoforms with a unique 5' untranslated exon. Molecular cloning
      demonstrates this ventral-specific exon lies within a 3.1-kb element that is
      duplicated in the opposite orientation 15-kb upstream to produce an interrupted
      palindrome and that similarity between the duplicated elements has been
      maintained by gene conversion. Orientation of the palindrome is reversed in A
      compared to AW, which suggests that mutation from one allele to the other is
      caused by intrachromosomal homologous recombination mediated by sequences within
      the duplicated elements. Analysis of 15 inbred strains of laboratory and wild
      derived mice with Southern hybridization probes and closely linked microsatellite
      markers suggests six haplotype groups: one typical for most strains that carry AW
      (129/SvJ, LP/J, CE/J, CAST/Ei), one typical for most strains that carry A
      (Balb/cJ, CBA/J, FVB/N, PERA/Rk, RBB/Dn); and four that are atypical (MOLC/Rk,
      MOLG/Dn, PERA/Ei, PERC/Ei, SPRET/Ei, RBA/Dn). Our results suggest a model for
      molecular evolution of the agouti locus in which homologous recombination can
      produce a reversible switch in allelic identity.

PMID- 8878693
TI  - A genetic linkage map of the male goat genome.
AB  - This paper presents a first genetic linkage map of the goat genome. Primers
      derived from the flanking sequences of 612 bovine, ovine and goat microsatellite
      markers were gathered and tested for amplification with goat DNA under
      standardized PCR conditions. This screen made it possible to choose a set of 55
      polymorphic markers that can be used in the three species and to define a panel
      of 223 microsatellites suitable for the goat. Twelve half-sib paternal goat
      families were then used to build a linkage map of the goat genome. The linkage
      analysis made it possible to construct a meiotic map covering 2300 cM, i.e., >
      80% of the total estimated length of the goat genome. Moreover, eight cosmids
      containing microsatellites were mapped by fluorescence in situ hybridization in
      goat and sheep. Together with 11 microsatellite-containing cosmids previously
      mapped in cattle (and supposing conservation of the banding pattern between this
      species and the goat) and data from the sheep map, these results made the
      orientation of 15 linkage groups possible. Furthermore, 12 coding sequences were
      mapped either genetically or physically, providing useful data for comparative
      mapping.

PMID- 8878694
TI  - Studies of the inheritance of human ribosomal DNA variants detected in two
      dimensional separations of genomic restriction fragments.
AB  - We have investigated the variation in human ribosomal DNA repeat units as
      revealed in two-dimensional electrophoretic separates of genomic restriction
      fragments that were end-labeled at NotI cleavage sites. The transcribed portion
      of the ribosomal DNA results in approximately 20 labeled fragments visible on
      each gel as multicopy spots. We have mapped these spots to the sequences
      responsible for their appearance on the gels, based on their migration positions
      and direct sequencing of spots, and describe several previously unreported
      sources of variation. By studying mother/father/child families we gained
      information on how much of the between-repeats variation is due to differences
      between and within repeat arrays on homologous chromosomes. Two instances in
      which a child exhibited more copies of a particular fragment than were present in
      the parents are described and hypothesized to be due to events such as multiple
      unequal sister-chromatid exchanges or gene conversions.

PMID- 8878695
TI  - A comparison of the structure and function of the highly homologous maize
      antioxidant Cu/Zn superoxide dismutase genes, Sod4 and Sod4A.
AB  - Two highly similar cytosolic Cu/Zn Sod (Sod4 and Sod4A) genes have been isolated
      from maize. Sod4A contains eight exons and seven introns. The Sod4 partial
      sequence contains five introns. The introns in both genes are located in the same
      position and have highly homologous sequences in several regions. The largest
      intron (> 1200 bp) interrupts the 5' leader sequence. The presence of different
      regulatory motifs in the promoter region of each gene may indicate distinct
      responses to various conditions. Zymogram and RNA blot analyses show that Sod4
      and Sod4A are expressed in all tissues of the maize plant. The developmental
      profiles of Sod4 and Sod4A mRNA accumulation differ in scutella during
      sporophytic development. RNA blot analysis of the respective Sod mRNAs indicates
      a differential, tissue-specific response of each gene to certain stressors. RNA
      isolated from stem tissue of ethephon-treated seedlings shows an increase in the
      Sod4 but not the Sod4A transcript while there is no change in transcripts of
      either gene in leaves or roots. There is differential mRNA accumulation between
      the two genes in leaf and stem tissue of paraquat-treated seedlings. Other agents
      that can cause oxidative stress were also tested for differential expression of
      the genes.

PMID- 8878696
TI  - Genome duplication in soybean (Glycine subgenus soja).
AB  - Restriction fragment length polymorphism mapping data from nine populations
      (Glycine max x G. soja and G. max x G. max) of the Glycine subgenus soja genome
      led to the identification of many duplicated segments of the genome. Linkage
      groups contained up to 33 markers that were duplicated on other linkage groups.
      The size of homoeologous regions ranged from 1.5 to 106.4 cM, with an average
      size of 45.3 cM. We observed segments in the soybean genome that were present in
      as many as six copies with an average of 2.55 duplications per segment. The
      presence of nested duplications suggests that at least one of the original
      genomes may have undergone an additional round of tetraploidization.
      Tetraploidization, along with large internal duplications, accounts for the
      highly duplicated nature of the genome of the subgenus. Quantitative trait loci
      for seed protein and oil showed correspondence across homoeologous regions,
      suggesting that the genes or gene families contributing to seed composition have
      retained similar functions throughout the evolution of the chromosomes.

PMID- 8878697
TI  - Marker-based inferences about epistasis for genes influencing inbreeding
      depression.
AB  - We describe a multilocus, marker-based regression method for inferring
      interactions between genes controlling inbreeding depression in self-fertile
      organisms. It is based upon selfing a parent heterozygous for several unlinked
      codominant markers, then analyzing the fitness of progeny marker genotypes. If
      loci causing inbreeding depression are linked to marker loci, then viability
      selection is manifested by distorted segregation of markers, and fecundity
      selection by dependence of the fecundity character upon the marker genotype. To
      characterize this selection, fitness is regressed on the proportion of loci
      homozygous for markers linked to deleterious alleles, and epistasis is detected
      by nonlinearity of the regression. Alternatively, fitness can be regressed on the
      proportion of heterozygous loci. Other modes of selection can be incorporated
      with a bivariate regression involving both homozygote and heterozygote marker
      genotypes. The advantage of this marker-based approach is that "purging" is
      minimized and specific chromosomal segments are identified; its disadvantage lies
      in low statistical power when linkage is not strong and/or the linkage phase
      between marker and selected loci is uncertain. Using this method in the
      wildflower Mimulus guttatus, we found predominant multiplicative gene interaction
      determining fecundity and some negative synergistic (nonmultiplicative)
      interaction for viability.

PMID- 8878698
TI  - Estimation of deleterious-mutation parameters in natural populations.
AB  - The rate and average effects of spontaneous deleterious mutations are important
      determinants of the evolution of breeding systems and of the vulnerability of
      small populations to extinction. Nevertheless, few attempts have been made to
      estimate the properties of such mutations, and those studies that have been
      performed have been extremely labor intensive, relying on long-term, laboratory
      mutation-accumulation experiments. We present an alternative to the latter
      approach. For populations in which the genetic variance for fitness is a
      consequence of selection-mutation balance, the mean fitness and genetic variance
      of fitness in outbred generations can be expressed as simple functions of the
      genomic mutation rate, average homozygous effect and average dominance
      coefficient of new mutations. Using empirical estimates for the mean and genetic
      variance of fitness, these expressions can then be solved to obtain joint
      estimates of the deleterious-mutation parameters. We employ computer simulations
      to evaluate the degree of bias of the estimators and present some general
      recommendations on the application of the technique. Our procedures provide some
      hope for obtaining estimates of the properties of deleterious mutations from a
      wide phylogenetic range of species as well as a mechanism for testing the
      validity of alternative models for the maintenance of genetic variance for
      fitness.

PMID- 8878699
TI  - Mutation-selection balance at a modifier-of-imprinting locus.
AB  - We propose a pair of population genetic models for a modifier-of-imprinting locus
      for which different genotypes imprint different proportions of an imprintable
      target locus in their gametes. The two models examine the situations in which
      imprinting is advantageous, and we discuss three cases for which the modifier is
      respectively partially dominant, dominant, or recessive. The models predict the
      stable equilibrium frequencies of the mutant modifier and functionally diploid
      individuals in a large population in terms of up to four parameters: the mutation
      rate at the modifier locus, nu; the selection coefficient against the
      disadvantageous phenotype, sigma; the proportion of unimprinted eggs produced by
      homozygotes for the mutant modifier, theta, and, in the partially dominant
      models, the dominance parameter, kappa. The equilibrium frequency of the mutant
      phenotypes is shown to be approximately twice that of standard Mendelian models:
      2 nu/sigma or 4nu/sigma when the modifier is recessive or dominant, respectively.
      Mathematical equivalences between these and nonimprinting models are noted.

PMID- 8878700
TI  - Dynamics of plant mitochondrial genome: model of a three-level selection process.
AB  - The plant mitochondrial genome is composed of a set of molecules of various sizes
      that generate each other through recombination between repeated sequences.
      Molecular observations indicate that these different molecules are present in an
      equilibrium state. Different compositions of molecules have been observed within
      species. Recombination could produce deleted molecules with a high replication
      rate but bearing little useful information for the cell (such as "petite" mutants
      in yeast). In this paper we use a multilevel model to examine selection among
      rapidly replicating incomplete molecules and relatively slowly replicating
      complete molecules. Our model simulates the evolution of mitochondrial
      information through a three-level selection process including intermolecular,
      intermitochondrial, and intercellular selection. The model demonstrates that
      maintenance of the mitochondrial genome can result from multilevel selection, but
      maintenance is difficult to explain without the existence of selection at the
      intermitochondrial level. This study shows that compartmentation into
      mitochondria is useful for maintenance of the mitochondrial information. Our
      examination of evolutionary equilibria shows that different equilibria (with
      different combinations of molecules) can be obtained when recombination rates are
      lower than a threshold value. This may be interpreted as a drift-mutation
      balance.

PMID- 8878701
TI  - On the potential for estimating the effective number of breeders from
      heterozygote-excess in progeny.
AB  - The important parameter of effective population size is rarely estimable directly
      from demographic data. Indirect estimates of effective population size may be
      made from genetic data such as temporal variation of allelic frequencies or
      linkage disequilibrium in cohorts. We suggest here that an indirect estimate of
      the effective number of breeders might be based on the excess of heterozygosity
      expected in a cohort of progeny produced by a limited number of males and
      females. In computer simulations, heterozygote excesses for 30 unlinked loci
      having various numbers of alleles and allele-frequency profiles were obtained for
      cohorts produced by samples of breeders drawn form an age-structured population
      and having known variance in reproductive success and effective number. The 95%
      confidence limits around the estimate contained the true effective population
      size in 70 of 72 trials and the Spearman rank correlation of estimated and actual
      values was 0.991. An estimate based on the heterozygote excess might have certain
      advantages over the previous estimates, requiring only single-locus and single
      cohort data, but the sampling error among individuals and the effect of
      departures from random union of gametes still need to be explored.

PMID- 8878702
TI  - Genetic distances and reconstruction of phylogenetic trees from microsatellite
      DNA.
AB  - Recently many investigators have used microsatellite DNA loci for studying the
      evolutionary relationships of closely related populations or species, and some
      authors proposed new genetic distance measures for this purpose. However, the
      efficiencies of these distance measures in obtaining the correct tree topology
      remains unclear. We therefore investigated the probability of obtaining the
      correct topology (PC) for these new distances as well as traditional distance
      measures by using computer simulation. We used both the infinite-allele model
      (IAM) and the stepwise mutation model (SMM), which seem to be appropriate for
      classical markers and microsatellite loci, respectively. The results show that in
      both the IAM and SMM CAVALLI-SFORZA and EDWARDS' chord distance (DC) and NEI et
      al.'s DA distance generally show higher PC values than other distance measures,
      whether the bottleneck effect exists or not. For estimating evolutionary times,
      however, NEI's standard distance and GOLDSTEIN et al.'s (delta mu)2 are more
      appropriate than other distances. Microsatellite DNA seems to be very useful for
      clarifying the evolutionary relationships of closely related populations.

PMID- 8878703
TI  - Polymorphism in genes that influence sperm displacement.
AB  - Paternity of offspring of multiply inseminated females is in many organisms
      highly skewed, with an advantage generally going to the male that most recently
      mated. Variation in sperm competitive ability can result in strong natural
      selection, and one expects that a gene that offers an advantage in sperm
      displacement would, all else being equal, be rapidly fixed, leaving low
      equilibrium levels of variability in sperm competition. However, empirical
      studies have demonstrated genetic variation in sperm displacement, begging the
      question of how this variation can be maintained. Here we develop a population
      genetic model to find conditions that maintain polymorphism in alleles that
      influence sperm displacement. We consider a one-locus model in which allelic
      variants have pleiotropic effects on fecundity and mating ability in addition to
      sperm displacement. This model can admit more than one stable polymorphism, and
      we find conditions for protected polymorphism. Induced overdominance is not
      necessary for stable polymorphism. These results have direct bearing on the
      observed variation in the ability of resident sperm to defend against
      displacement.

PMID- 8878704
TI  - Neutral genetic markers and conservation genetics: simulated germplasm
      collections.
AB  - This study examines the use of neutral genetic markers to guide sampling from a
      large germplasm collection with the objective of establishing from it a smaller,
      but genetically representative sample. We simulated evolutionary change and
      germplasm sampling in a subdivided population of a diploid hermaphrodite annual
      plant to create an initially large collection. Several strategies of sampling
      from this collection were then compared. Our results show that a strategy based
      on information obtained from marker genes led to retention of the maximum number
      of neutral and nonneutral alleles in the smaller sample. This occurred when demes
      were composed of self-fertilizing individuals or when no migration occurred among
      demes, but not when demes of an outcrossing population were connected by high
      levels of migration.

PMID- 8878705
TI  - The rate of compensatory evolution.
AB  - A two-locus model is presented to analyze the evolution of compensatory mutations
      occurring in stems of RNA secondary structures. Single mutations are assumed to
      be deleterious but harmless (neutral) in appropriate combinations. In proceeding
      under mutation pressure, natural selection and genetic drift from one fitness
      peak to another one, a population must therefore pass through a valley of
      intermediate deleterious states of individual fitness. The expected time for this
      transition is calculated using diffusion theory. The rate of compensatory
      evolution, kappa c, is then defined as the inverse of the expected transition
      time. When selection against deleterious single mutations is strong, kappa c
      becomes independent on the recombination fraction r between the two loci.
      Recombination generally reduces the rate of compensatory evolution because it
      breaks up favorable combinations of double mutants. For complete linkage, kappa c
      is given by the rate at which favorable combinations of double mutants are
      produced by compensatory mutation. For r > O, kappa c decreases exponentially
      with r. In contrast, kappa c becomes independent of r for weak selection. We
      discuss the dynamics of evolutionary substitutions of compensatory mutants in
      relation of WRIGHT's shifting balance theory of evolution and use our results to
      analyze the substitution process in helices of mRNA secondary structures.

PMID- 8878706
TI  - Heterozygosity, heteromorphy, and phylogenetic trees in asexual eukaryotes.
AB  - Little attention has been paid to the consequences of long-term asexual
      reproduction for sequence evolution in diploid or polyploid eukaryotic organisms.
      Some elementary theory shows that the amount of neutral sequence divergence
      between two alleles of a protein-coding gene in an asexual individual will be
      greater than that in a sexual species by a factor of 2tu, where t is the number
      of generations since sexual reproduction was lost and u is the mutation rate per
      generation in the asexual lineage. Phylogenetic trees based on only one allele
      from each of two or more species will show incorrect divergence times and, more
      often than not, incorrect topologies. This allele sequence divergence can be
      stopped temporarily by mitotic gene conversion, mitotic crossing-over, or ploidy
      reduction. If these convergence events are rare, ancient asexual lineages can be
      recognized by their high allele sequence divergence. At intermediate frequencies
      of convergence events, it will be impossible to reconstruct the correct phylogeny
      of an asexual clade from the sequences of protein coding genes. Convergence may
      be limited by allele sequence divergence and heterozygous chromosomal
      rearrangements which reduce the homology needed for recombination and result in
      aneuploidy after crossing-over or ploidy cycles.

PMID- 8878707
TI  - Pregnancy, ultrasound screening and smoking attitudes.
AB  - This questionnaire study was performed to evaluate screening as a tool to help
      reduce smoking among pregnant women and their partners. Three hundred women and
      their partners coming for ultrasound screening were asked to participate. Twenty
      two percent of the women and 21% of the men were smoking regularly before
      pregnancy. Fifty-four percent of the women changed their smoking habits after
      knowledge of the pregnancy and before the scan. The corresponding figure for men
      was 19%. Before the scan 54% of the women and 49% of the men estimated their
      ability to stop smoking later in pregnancy as higher than 50%. The scan itself
      did not increase this figure. Among women with high consumption of cigarettes,
      the estimated ability to stop smoking was low.

PMID- 8878708
TI  - Chorion villosum does not express progesterone and estrogen receptors during the
      first trimester of pregnancy.
AB  - First-trimester chorion villosum plays the key role in the development of human
      placenta and secretes a large number of hormones and hormone-related substances.
      To test whether progesterone and estrogen could have regulatory effects on first
      trimester chorion villosum functions, we investigated the presence of
      progesterone receptor (PR) and estrogen receptor (ER) in 47 chorion villosum
      samples from patients who underwent abortion during the first trimester of
      pregnancy. The study was carried out using immunohistochemical methods. No ER and
      PR positivity was evidenced in the 47 chorion villosum samples examined. The
      possibility that progesterone and estrogen play a role in the regulation of
      chorion villosum functions should therefore be excluded.

PMID- 8878710
TI  - Prenatal diagnosis of major congenital cardiovascular malformations.
AB  - This prospective study was designed to determine whether there would be a higher
      incidence of congenital cardiovascular malformation (CCVM) in pregnant women with
      certain risk factors. Fetal echocardiography, from second trimester of term, was
      performed in 1,659 pregnant women with risk factors for CCVMs and 826 pregnant
      women without risk factors from March 1990 to April 1995. Two-dimensional
      imaging, fetal M mode measurements, Doppler waveform velocity and Doppler color
      flow mapping were used for fetal heart examination. During this period, 70
      fetuses with major cardiovascular malformations were found. The prenatal
      detection rate was determined as 2.8% (70/2,485) in our study. The rate in the
      high-risk group, however, was 3.7% (61/1,659). Of all indications, fetal risk
      factors had the highest rate (9.3%, 46/494) of detected CCVMs. Maternal and
      familial indications could be excluded from the high-risk group as they did not
      show any increased incidence over the low-risk group. We suggest that fetal
      echocardiography is mandatory in the high-risk group, especially in cases with
      fetal and placental risk factors. Fetal cardiac screening in the hands of first
      line sonographers has a major role in prenatal diagnosis of CCVMs in the low-risk
      group.

PMID- 8878709
TI  - Mathematical modeling of fetal organ growth using the Rossavik growth model. V.
      Cerebellum.
AB  - Growth of the fetal cerebellum was monitored by transverse cerebellar diameter
      (CD) from 14 to 39 weeks menstrual age in 125 Japanese fetuses. The growth curve
      for this parameter was determine using a Rossavik growth model [p = c(t)k & (t)].
      An R2 value of 95.5% was obtained for CD. Variability analysis indicated a
      progressive increase in variability with fetal age for this parameter.
      Variability data were used with the growth curve model to determine a standard
      curve for this parameter. This standard curve provides a superior means to
      evaluate normal fetal cerebellar growth in the fetus and to identify cerebellar
      abnormalities in utero.

PMID- 8878711
TI  - Platelet angiotensin II receptor status during pregnancy in Chinese women at high
      risk of developing pregnancy-induced hypertension.
AB  - OBJECTIVES: The aims of this prospective study were to explore the changes in
      platelet angiotensin II (A-II) binding in pregnancy amongst Chinese women at high
      risk of developing pregnancy-induced hypertension (PIH) and the effects of low
      dose aspirin and calcium supplementation on A-II binding. METHODS: Platelet A-II
      binding was assayed in 15 non-pregnant women and in 63 pregnant women determined
      to be at risk of PIH on the basis of 2nd-trimester mean arterial pressure (MAP).
      The pregnant patients were randomized into three groups: control, low-dose
      aspirin, and calcium supplementation. A-II binding was assayed again during the
      3rd trimester in half the women and 8 weeks after delivery. RESULTS: A-II binding
      was negatively correlated with MAP measured in the left lateral position (p <
      0.05) but not with MAP measured in the supine position. There were no significant
      differences between A-II binding in non-pregnant and pregnant women. Neither low
      dose aspirin nor calcium supplementation caused significant reductions in A-II
      binding. CONCLUSION: The measurement of platelet A-II binding is unlikely to
      provide significant information regarding the risk of PIH over and above that
      obtained from measurement of 2nd-trimester MAP.

PMID- 8878712
TI  - Fibrinolysis during normal pregnancy and severe preeclampsia relationships
      between plasma levels of plasminogen activators and inhibitors.
AB  - The antigen levels of plasminogen activator inhibitor type 1 (PAI-1), plasminogen
      activator inhibitor type 2 (PAI-2), tissue-type plasminogen activator (t-PA), and
      urokinase-type plasminogen activator (u-PA) were measured during pregnancy and
      severe preeclampsia. The PAI-1 and PAI-2 antigen levels increased linearly during
      pregnancy and promptly returned to the level of non-pregnant women after
      delivery. The t-PA and u-PA antigen levels increased slowly and linearly during
      pregnancy. In severe preeclampsia, the PAI-2 antigen level was lower than that
      observed during the 3rd trimester of normal pregnancy, and the t-PA antigen level
      was higher than that during the 3rd trimester of normal pregnancy.
      Immunohistochemical examination of placental tissue showed that the PAI-2 and u
      PA antigens were localized in syncytiotrophoblasts. In severe preeclampsia, the
      PAI-2 and u-PA antigens in placental tissue did not stain as clearly as during
      the 3rd trimester of normal pregnancy. The PAI-2 and u-PA antigen levels showed a
      positive correlation with birth weight. Therefore, PAI-2 may be an important
      marker of placental function and abnormality in pregnancies.

PMID- 8878713
TI  - Cord blood cytokines and soluble adhesion molecules in vaginal and cesarean
      delivered neonates.
AB  - OBJECTIVE: Our purpose was to evaluate the effect of labor pain on the
      concentrations of cytokines and soluble adhesion molecules in cord blood.
      METHODS: Umbilical cord interleukin-6 (IL-6), interleukin-8 (IL-8), tumor
      necrosis factor-alpha (TNF-alpha), granulocyte elastase (GEL), intercellular
      adhesion molecule-1 (ICAM-1), and endothelial lymphocyte adhesion molecule-1
      (ELAM-1) were measured in 21 normal appropriately grown newborns delivered
      vaginally (VD group), and 20 normal appropriately grown newborns delivered by
      elective cesarean section (ECS group). Umbilical cord arterial blood pH and PO2
      were also measured. RESULTS: Umbilical artery blood pH and PO2 in the VD group
      were not significantly different from those in the ECS group. There were no
      significant differences for concentrations of IL-6, IL-8, TNF-alpha, GEL, ICAM-1,
      and ELAM-1 in cord blood between VD and ECS groups. CONCLUSION: These results
      suggests that labor pains do not affect the concentrations of cytokines and
      soluble adhesion molecules in cord blood.

PMID- 8878714
TI  - Is intertwin birth weight discordance predictable?
AB  - OBJECTIVE: To compare the efficacies of intertwin difference in abdominal
      circumferences (ACs) and estimated fetal weight (EFWs) to predict birth weight
      discordance in twin gestations. METHODS: Ninety pairs of twins with sonographic
      measurements of AC and femur length, performed within 2 weeks before delivery,
      were included in the study. The EFW was calculated (Hadlock's formula). We used
      Bayes' theorem and the Mantel-Haenszel chi 2 test to calculate and compare the
      rates of false-positive and false-negative prediction of the cutoff values of 15,
      20, and 25% intertwin birth weight discordance by the intertwin EFW difference
      and an intertwin AC difference of > or = 18 mm. RESULTS: There were no
      significant difference between the two methods to predict birth weight
      discordance at 15-25% discordance (p = 0.254, OR = 0.33, 95% CI = 1.45-0.24) and
      at > 25% discordance (p = 0.112, OR 0.18, 95% CI = 0.03-1.34). CONCLUSIONS: Both
      the intertwin AC difference (> or = 18 mm) and intertwin EFW difference have
      similar negative predictive values and the same efficacy to exclude discordant
      growth. Because of the relatively low positive predictive values, birth weight
      discordance cannot be accurately predicted by either method.

PMID- 8878715
TI  - Intra-amniotic Chlamydia trachomatis infection.
AB  - Chlamydia trachomatis is one of the most prevalent genital pathogens in pregnant
      women. Ascending, transcervical infection may reach fetal membranes creating
      chorioamnionitis or amniotic fluid infection. The aim of this study was to
      examine amniotic fluids obtained during cesarean section for the presence of
      chlamydial IgM- and IgG-specific antibodies, and for the presence of C.
      trachomatis antigen. Five of 52 (9.6%) amniotic fluid samples were seropositive.
      Two of 52 (3.8%) amniotic fluid samples had C. trachomatis antigen in the
      epithelial cells of the amnion. In conclusion, our data indicate that there is a
      high rate of transmission of C. trachomatis from mother to infant and that the
      pathogen can be identified in the amniotic fluid.

PMID- 8878716
TI  - Factors associated with withdrawal bleeding after administration of oral
      dydrogesterone or medroxyprogesterone acetate in women with secondary amenorrhea.
AB  - The effectiveness of two treatment regiments in inducing withdrawal bleeding in
      secondary amenorrhea was compared and correlated with the endometrial thickness
      and endogenous E2 and progesterone concentrations. A prospective, randomized and
      double-blind study was designed at the Outpatient Clinic of Reproductive
      Endocrinology, Central Emek Hospital, Afula, Israel. Seventy-seven premenopausal
      women with oligomenorrhea or amenorrhea, 48 of whom qualified for the study,
      underwent a 5-day course of either medroxyprogesterone acetate (MPA) 5 mg b.i.d.
      or dydrogesterone (DG) 10 mg b.i.d. Endogenous pretreatment values of E2 and
      progesterone and endometrial thickness (by transvaginal ultrasonography) were
      correlated with the bleeding response. Withdrawal bleeding occurred in 93% of
      women taking either MPA or DG. Side effects occurred similarly among the groups.
      Lipid concentrations were unchanged. Endogenous E2 and progesterone were limited
      predictive value for withdrawal bleeding. Endometrial thickness as measured by
      transvaginal sonography correlated significantly with the bleeding response.

PMID- 8878717
TI  - Estradiol and progesterone endometrial receptors and body fat distribution in
      obese women.
AB  - The content of endometrial receptors for estradiol (ER) and progesterone (PR) was
      determined in three groups (10 women each) classified with respect to body fat
      distribution: (1) normal, nonobese; (2) lower body segment obesity and (3) upper
      body segment obesity. The ER in group 3 were significantly (p < 0.05) higher than
      those of group 1. As regards PR, no statistical differences were found among the
      three groups. These findings demonstrate different endometrial ER concentrations
      in obese women according to body fat distribution, greater in upper segment
      obesity. Probably the lack of progesterone as well as other factors in the
      endocrine milieu of these patients may determine the differences found;
      therefore, future research on this matter should be carried out.

PMID- 8878718
TI  - Premenopause-dependent changes.
AB  - The authors retrospectively evaluated 1,773 climacteric outpatients in order to
      establish: (a) criteria able to distinguish different conditions in the
      transitional phase before menopause (advanced fertile age and premenopause) and
      (b) premenopause-related changes during the transition from one to the other of
      several clinical and laboratory parameters. Results showed an increase in
      gonadotropin plasma levels, a decrease in estrogen plasma levels and a greater
      frequency of women complaining of hot flushes in premenopause compared to
      advanced fertile age, as an expression of the progressive decline of ovarian
      function. Premenopause-related changes were a decrease in thyroid function and an
      increase in the body mass index, the beginning of bone loss, an increase in
      glucose, total cholesterol and triglyceride serum levels and a greater frequency
      of women complaining of hypertension and urinary stress incontinence. An increase
      in total proteins, uric acid and aminotransferase serum levels was also noted.

PMID- 8878719
TI  - Cytological evaluation and molecular human papillomavirus test of cervical
      scrapings from women treated for condyloma.
AB  - The incidence of cervical carcinoma has decreased by about half since cytological
      screening was introduced in Sweden in the 1960s. This is an encouraging but not
      altogether satisfactory development. Human papillomaviruses (HPVs) are known to
      be potential agents in the etiology of cervical cancer. Therefore, an additional
      HPV test might well improve the detection rate of high-grade cervical
      intraepithelial neoplasia (CIN). The purpose of this investigation was to compare
      the correlation of cytology and HPV testing in a pilot study of 94 women
      recruited from a clinic for sexually transmitted diseases after condyloma
      treatment and to check earlier established molecular biological assays. Cervical
      scrapings, taken for simultaneous Pap smear and molecular HPV DNA testing, were
      assessed by the polymerase chain reaction. Of the 94 women tested, 47 (50%) had
      normal cytology and negative HPV DNA; 36 (38%) had normal cytology but positive
      HPV DNA, 26 (72%) of whom harbored high-risk HPVs; 1 (1%) had abnormal cytology
      but negative HPV DNA, and 10 (11%) had abnormal cytology and positive HPV DNA, 5
      (50%) of whom harbored high-risk HPVs. It is concluded that an HPV test would add
      greater specificity and possibly also greater sensitivity to cytology for
      detecting or predicting high-grade CIN. This information may be of value when
      designing future gynecological screening programs.

PMID- 8878720
TI  - Does primary omental pregnancy exist?
AB  - Omental pregnancy is a rare form of abdominal pregnancy. In the 5 previously
      reported cases, primary implantation of the embryo to the omentum has been
      proposed as its etiology. We present a new case of omental pregnancy in a 31-year
      old woman presenting with symptoms of ectopic pregnancy. After careful review of
      our case and the published literature in view of the accepted definition of
      primary abdominal pregnancy, we conclude that all reported instances of omental
      pregnancy are secondary and probably follow tubal or ovarian pregnancy abortion.

PMID- 8878721
TI  - Successful outcome of idiopathic nonimmune hydrops fetalis treated by maternal
      digoxin.
AB  - Nonimmune hydrops fetalis (NIHF), occurring in 1 in 2,500-3,000 live births has a
      reported mortality rate of 50-98%. A similar mortality rate for intrauterine
      death of fetuses with NIHF probably exists. Many fetal pathological entities have
      been implicated as causing the condition, but to date, treatment has only been
      found for cases of fetal tachycardia complicated with hydrops. During a routine
      ultrasonographic survey of a woman at 32 weeks of gestation, we detected a fetus
      with severe ascites. There was no apparent etiology, and although no tachycardia
      was evident, low dosage transplacental digoxin therapy was immediately initiated.
      The hydropic condition completely resolved within 17 days and at 39 weeks of
      gestation, a perfectly normal baby was born after a spontaneous and uneventful
      labor. This is the first report of successful treatment of idiopathic NIHF with
      maternal digoxin.

PMID- 8878722
TI  - Low-dose dopamine in treating acute renal failure caused by preeclampsia.
AB  - Acute renal failure is a serious complication of preeclampsia that usually
      requires the termination of pregnancy. We present a case of acute renal failure
      due to severe preeclampsia successfully treated with the infusion of a low dose
      of dopamine. This 25-year-old Japanese primigravida was admitted at 31 weeks of
      gestation for the treatment of preeclampsia. Urine output was decreased to 380
      ml/day; 24-hour creatinine clearance was decreased to 13.7 liters/day. Blood urea
      nitrogen was elevated to 31.9 mg/dl; serum creatinine was elevated to 3.34 mg/dl.
      The diagnosis was acute renal failure related to preeclampsia. A low dose of
      dopamine, 1 microgram/kg/min, was infused daily for 7 days at 32 weeks of
      gestation to maintain urine output. Renal function improved markedly without any
      adverse effect on the patient's blood pressure which was controlled on
      hydralazine. Fetal distress developed 4 days later and emergency cesarean section
      was performed. A healthy female was delivered. The infusion of a low dose of
      dopamine appeared to be highly effective in managing acute renal failure caused
      by preeclampsia with no serious side effects.

PMID- 8878723
TI  - Early detection of 'endometrial resection syndrome'.
AB  - We report a patient who developed symptoms of fluid overload after having
      absorbed 3 litres of irrigating fluid during transcervical resection of the
      endometrium. Four methods were used to measure the absorption at 10-min intervals
      throughout the operation. There were strong intercorrelations between the results
      of these monitoring methods, which consisted in breath ethanol analyses and
      measurements of the serum sodium and glycine concentrations and of the volumetric
      fluid balance. However, the ethanol method was easiest to perform and provided
      immediate results. This monitoring gave the operating team as much as 45 min to
      prevent further absorption before it became large enough to elicit a
      transcervical endometrial resection syndrome.

PMID- 8878724
TI  - Purchasing implantable pacemakers. Part 1: Optimizing the purchase of implantable
      pacemakers.

PMID- 8878725
TI  - Purchasing implantable pacemakers. Part 2: The implantable pacemaker market.

PMID- 8878727
TI  - Barotrauma from CPAP systems lacking pressure relief.

PMID- 8878726
TI  - Oxygen concentrators.

PMID- 8878728
TI  - Water pump failure in SIMS level 1 HotLine fluid warmers.

PMID- 8878729
TI  - Wear causes lack of gas concentration display in Criticare Model 1100 multiple
      medical gas monitors.

PMID- 8878730
TI  - Response of the blast stem cells of acute myeloblastic leukemia to G-CSF, GM-CSF,
      or the ligand for C-KIT, alone or in combination.
AB  - Growth factors are commonly included in protocols for the treatment of acute
      myeloblastic leukemia (AML). Because the response of blast stem cells in culture
      to growth factors might influence the contribution of factor to clinical outcome,
      we studied 42 patients with AML or severe myelodysplasia. Peripheral blood blast
      cells were cultured in a clonogenic assay at three cell concentrations and with
      the following combinations of growth factors: no added growth factor (NF), G-CSF,
      GM-CSF, Kit ligand (KL), G-CSF + KL, GM-CSF + KL, and G-CSF + GM-CSF + KL. The
      slope of the line relating cell number plated to colony formation was calculated
      by least squares. The slopes were used to form three equally sized groups of
      patients. Marked heterogeneity was found in response of the blast populations to
      factor. A few general conclusions emerged: (1) autonomous blast populations are
      very rare; (2) although usually a population responds better to one of the growth
      factors than to others, seldom is the response exclusively to one factor; (3)
      when more than one factor is included in the cultures, synergism is usually seen.
      Significant associations were seen between successful remission induction for low
      slope values in cultures with NF or KL alone. For remission, but not survival,
      associations were found with intermediate values of slope in cultures with G-CSF
      + KL and GM-CSF + KL. We conclude that measurements of growth factor response are
      feasible and yield clinically useful data.

PMID- 8878731
TI  - Acquired type 2A von Willebrand disease in chronic myelocytic leukemia.
AB  - Acquired von Willebrand disease (vWD) has been described in a few patients with
      chronic myelocytic leukemia (CML). We present here acquired type 2 vWD associated
      with CML and provide characterization of an inhibitor to von Willebrand factor
      (vWF) from this patient. His bleeding time was prolonged. Ristocetin-induced
      platelet agglutination was abolished whereas botrocetin-mediated aggregation was
      normal. Multimeric analysis of vWF from patient's plasma showed that larger sizes
      of multimers were reduced. His past and family histories were negative for
      bleeding tendency. These results suggested that acquired type 2 vWD was present
      during his clinical course. The inhibitor was purified by Staphylococcal protein
      A, suggesting an IgG antibody. Both binding of 125I-vWF to GPIb and platelet
      agglutination by ristocetin were inhibited by the patient IgG with the
      concentrations of competing substances necessary to inhibit specific binding by
      50% (IC50s) of 260 micrograms/ml and 420 micrograms/ml, respectively. However,
      the IgG had no effect on these studies mediated by botrocetin. The IgG only
      reacted with intact vWF and a 39/34 kDa fragment of vWF. These results indicate
      that the recognition of GPIb binding site(s) on vWF by the IgG is a central
      pathogenesis of acquired type 2 vWD in this case.

PMID- 8878732
TI  - Differential diagnosis of L26-positive, CD15-negative Hodgkin's disease and large
      B-cell lymphoma with a high content of reactive T-cells: a morphologic and
      immunohistochemical study.
AB  - B-cell non-Hodgkin's lymphomas with a marked preponderance of reactive T cells,
      so-called T-cell rich B-cell lymphomas (TCRBCLs), can be morphologically confused
      with Hodgkin's disease (HD). To establish helpful distinguishing features in
      paraffin sections, 10 cases of L26-positive, CD15-negative HD and 10 cases of
      TCRBCL were compared; 4 cases of HD had morphologic features of the nodular
      lymphocyte predominant (LP) type. Nine of 10 cases of HD contained fewer than 20
      mitoses/20 high power fields (hpf) and only 1 had pericapsular involvement. In
      contrast, 9 of 10 TCRBCL had greater than 20 mitoses/20 hpf and 7 had perinodal
      infiltration. HDLP was easily distinguished from TCRBCL by the expanded dendritic
      meshworks outlining the L & H nodules and the high content of CD57-positive
      lymphocytes. The remaining 6 cases of non-LP L26-positive HD had a relatively
      distinctive immunostaining pattern, with absence of CD45 and discordant
      reactivity for L26 and Ki-B5 in Reed-Sternberg cells and variants. Only 3 cases
      of TCRBCL had a similar CD45 and L26/Ki-B5 immunostaining pattern, and these
      could be distinguished by demonstrable cytoplasmic light-chain restriction. These
      results show that evaluation of the mitotic count, pericapsular involvement, and
      immunohistochemical staining patterns for Ki-M4p, CD57, L26/Ki-B5, and CD45 can
      help to discriminate TCRBCL from L26-positive HD when only fixed material is
      available.

PMID- 8878733
TI  - Increased expression of the high-affinity receptor for IgG (FcRI, CD64) on
      neutrophils in multiple myeloma.
AB  - The surface expression of effector cell molecules on neutrophils was examined in
      19 patients with multiple myeloma (MM), 6 patients with monoclonal gammopathy of
      undetermined significance (MGUS) and 22 healthy control subjects. The expression
      of Fc receptors for IgG (FcR), complement receptors (CR), and cellular adhesion
      molecules on neutrophils was determined by flow cytometry and monoclonal
      antibodies. MM neutrophils exhibited higher expression of FcRI, CR3, and CR4 and
      lower expression of FcRII and L-selectin than that in MGUS and controls.
      Granulocyte colony-stimulating factor (G-CSF, 50 micrograms/m2/d) was
      administered subcutaneously to 8 patients with MM and to 4 healthy volunteers. G
      CSF administration increased the expression of FcRI, FcRII, and CR1 on
      neutrophils and decreased the expression of FcRIII on neutrophils in both groups.
      The application of G-CSF also resulted in increase of CR3 and CR4 expression and
      in decrease of L-selectin expression on neutrophils in healthy volunteers but not
      in MM patients. These findings suggest that MM neutrophils may be activate in
      vivo and that effector cell molecular expression on MM neutrophils is further
      modulated by G-CSF application.

PMID- 8878734
TI  - Fatal thrombotic thrombocytopenic purpura (TTP) presenting concurrently with
      metastatic multiple endocrine neoplasia (MEN) type I.
AB  - A 44-year-old women was treated for hyperparathyroidism resulting from
      parathyroid hyperplasia. Several months later, following a flu-like episode, she
      developed fever, confusion, abdominal pain, and diffuse petechiae, with severe
      thrombocytopenia and hemolytic anemia. She died on the 11th day of
      hospitalization. At autopsy she had multiple endocrine neoplasia type I, with two
      islet cell tumors, adrenal adenoma, pituitary adenoma, and bronchial carcinoid
      with liver metastasis. Florid visceral microthrombi involved arterioles and
      capillaries of the heart, including the conduction system. Brain, kidney,
      pancreas, adrenal, and portal areas of the liver were also heavily involved, but
      thrombi were rare in the liver sinusoids and the lungs. PAS-positive
      subendothelial deposits were demonstrated. In spite of the disseminated
      malignancy, the morphologic and laboratory findings were inconsistent with
      disseminated intravascular coagulation (DIC), and supported the clinical
      diagnosis of TTP. To the best of our knowledge this is the first report
      association of TTP with MEN and raises the question of a genetic linkage and/or
      hormonal interaction.

PMID- 8878736
TI  - Associative long-term depression in the hippocampus in vitro.
AB  - An association between the test and conditioning stimuli is critical for
      determining the nature of their interaction during learning and memory. Two
      experimental protocols which result in the induction of associative forms of long
      term depression (LTD) at Schaffer collateral synapses onto CA1 pyramidal cells in
      vitro are reviewed in this article. The requirements for the induction of LTD
      with these protocols are discussed, as well as the relationship between these
      forms of associative LTD and so-called homosynaptic LTD. In particular, the
      biological basis of the experimentally demonstrated necessity for temporal and
      spatial conjunction between the test and conditioning stimuli is examined.

PMID- 8878735
TI  - Intracellular studies of heterosynaptic long-term depression (LTD) in CA1 of
      hippocampal slices.

PMID- 8878737
TI  - Dendritic calcium channels and hippocampal long-term depression.
AB  - The authors examine the potential role of the different sources of dendritic Ca2+
      influx in long-term depression (LTD) of synaptic efficacy. Recent data on the
      location and functional distribution of voltage-gated Ca2+ channels obtained from
      fluorescence imaging and patch clamp experiments are presented. This is followed
      by a discussion of the existing evidence for different sources of Ca2+ playing a
      role in the induction of LTD. The authors conclude that a number of key issues
      need to be resolved before any conclusions are drawn as to the involvement of any
      specific route of Ca2+ entry in LTD.

PMID- 8878738
TI  - Homosynaptic LTD and depotentiation: do they differ in name only?
AB  - Long-term depression (LTD) now occupies a major place in theories of the cellular
      basis of learning and memory and other nervous system phenomena involving
      persistent changes in synaptic responsiveness. LTD can be induced using a variety
      of stimulation paradigms. Homosynaptic LTD in this review refers to a depression
      of basal responses that is restricted to the pathway that has been stimulated by
      a low-frequency (1 Hz) stimulus train. Despite the intensive interest in LTD,
      there has been controversy about the ease with which LTD can be induced and
      reports range from no success to routine success. There has been much less
      controversy about a related form of response depression now called
      "depotentiation" which shares many similarities with LTD. Depotentiation is the
      response reduction that affects, not the basal responses affected by LTD, but
      responses that have been increased by the process of long-term potentiation
      (LTP). LTD and depotentiation can be induced by similar stimulation and have many
      biochemical properties in common, but it has not been clear whether or not they
      represent the same phenomenon, in part because it often occurs that the same
      preparation that does not undergo LTD readily expresses depotentiation. We review
      work that indicates that the major differences between LTD and depotentiation
      involve age-dependence, the need for priming stimulation and sensitivity to GABA
      receptor antagonists. We present a hypothetical model that can reconcile the
      apparent disparities between LTD and depotentiation.

PMID- 8878739
TI  - LTD: many means to how many ends?
AB  - Several forms of long-term synaptic depression (LTD) have been identified in the
      hippocampus. Although these LTDs differ in their methods of induction, it remains
      unclear whether they converge upon some final common mechanism(s) of expression.
      In the present paper we review critical aspects of heterosynaptic and
      homosynaptic LTD induction and consider those findings relevant to the expression
      of each. In addition, we suggest several experimental approaches which may be of
      benefit in addressing the commonality of LTD expression mechanisms.

PMID- 8878740
TI  - LTD, LTP, and the sliding threshold for long-term synaptic plasticity.
AB  - LTD of synaptic transmission is a form of long-term synaptic plasticity with the
      potential to be as significant as LTP to both the activity-dependent development
      of neural circuitry and adult memory storage. In addition, interactions between
      LTP and LTD and the dynamic regulation of the gain of synaptic plasticity
      mechanisms are also very important. In particular, the computational ability of
      LTD to properly counterbalance LTP may be essential to maintaining synaptic
      strengths in the linear range, and to maximally sharpen the ability of synapses
      to compute and store frequency-based information about the phase relation between
      synapses. Experimental data confirm the presence of an activity-dependent
      "sliding threshold" with the expected properties. That is, when levels of
      neuronal activity are high, indicating circumstances increasing the likelihood of
      inducing LTP, compensatory changes cause the suppression of LTP and an enhanced
      likelihood of LTD. Conversely, we would predict that low levels of synaptic
      activity would shift the threshold in favor of greater LTP and less LTD, a
      hypothesis which has yet to be tested. The sliding threshold for LTP and LTD also
      has implications for underlying cellular mechanisms of both forms of long-term
      synaptic plasticity. If the thresholds for LTP and LTD are tightly and
      reciprocally co-regulated, that could imply that at least one component of LTD is
      a true depotentiation caused by reversal of a change mediating LTP. If so, the
      intuitively simplest hypothesis is that phosphorylation of AMPA glutamate
      receptors causes LTP of synaptic e.p.s.p.s, while dephosphorylation of the same
      site or sites causes depotentiation LTD. Of course, this hypothesis would refer
      only to a postsynaptic component of both LTP and LTD. There has been a recent
      report that, in neonatal rat hippocampus, a form of LTD that is expressed
      developmentally earlier than LTP appears to have a postsynaptic induction site,
      but is expressed as decreased presynaptic transmitter release (Bolshakov and
      Siegelbaum, 1994). Whether these properties will be retained as LTD matures is
      unknown, as is the likelihood that, if a component of LTP is expressed
      presynaptically, depotentiation of that presynaptic component can also occur.
      Equally unclear is the persistence of LTD relative to LTP. The few rigorous long
      term anatomical studies available suggest that the latest phases of LTP may be
      expressed as changes in dendritic spine shapes and/or synaptic morphology. While
      heterosynaptic LTD has been reported to have a duration of weeks in vivo (Abraham
      et al., 1994), we do not know whether LTP-induced morphological changes that take
      many days to appear can be reversed in an activity-dependent manner. An important
      feature of the consolidation of memories may turn out to be the slow development
      of LTP that is resistant to reversal by LTD. While we still at an earlier stage
      in our understanding of the mechanisms underlying LTD compared to LTP, some
      things are becoming clear. LTD is induced by afferent neuronal activity that is
      relatively ineffective in exciting the postsynaptic cell--an "anti-hebbian"
      condition. This property, coupled with the hebbian properties of LTP and the
      dynamic nature of membrane conductances, necessarily confers upon synapses the
      ability to compute and store the results of a covariance function. However, the
      role of such a computation in processing and/or memory is unclear. In addition,
      LTD appears to require the activation of NMDA and metabotropic subtypes of
      glutamate receptors, release of Ca2+ from intracellular stores, and an increase
      in intracellular [Ca2+] that is lower than that necessary to induce LTP. The
      early evidence is consistent with some overlap of targets for modification by LTP
      and LTD, with some forms of LTD likely to be a reversal, or "depotentiation," of
      previous LTP, perhaps through dephosphorylation of AMPA receptors.

PMID- 8878742
TI  - Low-frequency trains of paired stimuli induce long-term depression in area CA1
      but not in dentate gyrus of the intact rat.
AB  - We have examined the efficacy of a recently introduced protocol for inducing
      homosynaptic long-term depression (LTD) in area CA1 of the anesthetized rat
      (Thiels et al. [1994] J Neurophysiol 72:3009-3116.). In area CA1 of the awake
      animal, this protocol, consisting of 200 pairs of pulses delivered at 0.5 Hz,
      with an interpulse interval of 25 ms, consistently produced LTD, provided the
      initial pulse was sufficiently strong to produce significant paired-pulse
      depression of the evoked response. We extended these experiments to the dentate
      gyrus, using either paired pulses given to the perforant path in the awake adult
      rat, or, in the anesthetized adult, a two-pathway pairing procedure, in which the
      first pulse was delivered to the commissural input to the dentate gyrus and the
      second to the perforant path. In both cases, the first pulse led to substantial
      suppression of the response evoked by the second pulse. With neither protocol,
      however, was there any evidence for LTD or depotentiation. Paired-pulse
      stimulation of the perforant path of young rats (10-11 days) also failed to
      induce LTD or depotentiation of the population excitatory postsynaptic potential
      (EPSP). Thus, the dentate gyrus in the intact animal appears to be less
      susceptible to LTD and depotentiation than area CA1, a conclusion consistent with
      previous experiments in which we found that stimulation at 1-5 Hz produced
      LTD/depotentiation in area CA1 of young (but not adult) rats in vivo but was
      ineffective at any age in the dentate gyrus. Our results do not rule out the
      possibility that other, untested protocols may produce homosynaptic LTD and/or
      depotentiation in the dentate gyrus in vivo.

PMID- 8878741
TI  - NMDA receptor-dependent LTD in different subfields of hippocampus in vivo and in
      vitro.
AB  - In simulations with artificial neural networks, efficient information processing
      and storage has been shown to require that the strength of connections between
      network elements has the capacity to both increase and decrease in a use
      dependent manner. In contrast to long-term potentiation (LTP) of excitatory
      synaptic transmission, activity-dependent long-term depression (LTD) has been
      difficult to demonstrate in forebrain in vivo. Theoretical arguments indicate
      that coincidence of presynaptic excitation and low-magnitude postsynaptic
      activation are the necessary prerequisites for LTD induction. Here we report that
      stimulation paradigms which cause 1) sufficient excitation to result in NMDA
      receptor activation and simultaneously 2) attenuate the level of postsynaptic
      activation by recruitment of GABAA receptor-mediated inhibition consistently
      produce LTD of commissural input to area CA1 in the hippocampus of anesthetized
      adult rats, and of the perforant path input to the dentate gyrus in the
      hippocampus of anesthetized and unanesthetized adult rabbits. A functionally
      similar pre- and postsynaptic activation pattern applied to the hippocampal slice
      preparation by injecting hyperpolarizing current into the postsynaptic cell
      during NMDA receptor-mediated excitation also was effective in consistently
      inducing LTD. Results of studies in vitro show that Ca2+ influx through the NMDA
      channel is necessary for the induction of LTD, and moreover, that NMDA receptors
      also participate in the expression of LTD. Our findings demonstrate a general
      mechanism for the implementation of a theoretically derived learning rule in
      adult forebrain in vivo and in vitro and provide justification for the inclusion
      of use-dependent decreases of connection weights in formal models of cognitive
      processing.

PMID- 8878743
TI  - Synaptic plasticity during the cholinergic theta-frequency oscillation in vitro.

PMID- 8878744
TI  - Homosynaptic and heterosynaptic changes in driving of dentate gyrus interneurons
      after brief tetanic stimulation in vivo.
AB  - This study addressed changes in interneuron driving in the dentate gyrus (DG) of
      urethane-anaesthetized rats in response to tetanic stimulation of the perforant
      path (PP) or the converging dentate commissural pathway (CP). Using an
      extracellular tungsten electrode, we recorded from putative interneurons in the
      DG that fired to stimulation of both the PP and the CP. Conditioning trains (400
      Hz, 17.5 ms) were delivered to each pathway individually and to the two pathways
      together. The primary measure of synaptic drive was the latency of interneuron
      discharge. High-intensity PP tetany, CP tetany, and paired tetany consistently
      reduced firing latency to CP driving (P < .05 for all three), indicating an LTP
      like increase in synaptic activation through the CP. High-intensity PP tetany
      decreased latency to PP driving in only two of seven cases. Heterosynaptic
      changes occurred frequently in individual experiments. Activity-mediated
      adjustments in synaptic driving of inhibitory interneurons could play a role in
      normal physiological function.

PMID- 8878745
TI  - Pyramidal cells and stratum lacunosum-moleculare interneurons in the CA1
      hippocampal region share a GABAergic spontaneous input.
AB  - Patch-clamp technique was used in the CA1 region of the hippocampal rat slice
      preparation in order to perform a comparison between synaptic GABAergic
      spontaneous postsynaptic currents (sPSCs) recorded from pyramidal cells (PCs) of
      stratum pyramidale (SP) and interneurons of stratum-lacunosum moleculare (SL-M
      INs). GABAergic sPSCs from PCs and from SL-M INs displayed similar frequency
      (0.75 +/- 0.26 Hz vs. 0.53 +/- 0.11 Hz, respectively), amplitude (34.6 +/- 5.0 pA
      vs. 39.6 +/- 4.1 pA), rise-time (2.9 +/- 0.4 ms vs. 3.2 +/- 0.3 ms), and decay
      time (31.7 +/- 1.5 vs. 32.3 +/- 2.4). Agonists of receptors for endogenously
      released transmitters were bath-applied to induce variations in the frequency of
      sPSCs. Spontaneous PSC frequency increased after carbachol and trans-1
      aminocyclopentane-1,3-dicarboxilic acid (t-ACPD), whereas it decreased after 5
      hydroxy-tryptamine (5-HT) and baclofen in both classes of cells. Cross
      correlation analysis of double-patch recordings (one PC and one SL-M IN) revealed
      4.4 times as many coincident events as would be expected at random. The ratio
      between measured and random coincidences did not vary when the sPSCs frequency
      was increased. These results suggest that the same class of spontaneously active
      GABAergic cells impinge both on PCs and on SL-M INs, exerting control over them
      by varying the level of released GABA.

PMID- 8878746
TI  - Dendritic electrogenesis in rat hippocampal CA1 pyramidal neurons: functional
      aspects of Na+ and Ca2+ currents in apical dendrites.
AB  - The regenerative properties of CA1 pyramidal neurons were studied through
      differential polarization with external electrical fields. Recordings were
      obtained from somata and apical dendrites in the presence of 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), DL-2-amino-5-phosphonovaleric acid (APV), and
      bicuculline. S+ fields hyperpolarized the distal apical dendrites and depolarized
      the rest of the cell, whereas S divided by fields reversed the polarization.
      During intradendritic recordings, S+ fields evoked either fast spikes or compound
      spiking. The threshold response consisted of a low-amplitude fast spike and a
      slow depolarizing potential. At higher field intensities the slow depolarizing
      potential increased in amplitude, and additional spikes of high amplitude
      appeared. During intrasomatic recordings, S+ field evoked repetitive firing of
      fast spikes, whereas S divided by fields evoked a slow depolarizing potential on
      top of which high- and low-amplitude spikes were evoked. Tetrodotoxin (TTX)
      blocked all types of responses in both dendrites and somata. Perfusion with
      Ca(2+)-free, Co(2+)-containing medium increased the frequency and amplitude of
      fast spikes evoked by S+ field and substantially reduced the slow depolarizing
      potential evoked by S+ field and substantially reduced the slow depolarizing
      potential evoked by S divided by fields. Antidromic stimulation revealed that an
      all-or-none dendritic component was activated in the distal apical dendrites by
      back-propagating somatic spikes. The dendritic component had an absolute
      refractory period of about 4 ms and a relative refractory period of 10-12 ms.
      Ca(2+)-dependent spikes in the dendrites were followed by a long-lasting
      afterhyperpolarization (AHP) and a decrease in membrane input resistance, during
      which dendritic excitability was selectively reduced. The data suggest that
      generation of fast Na+ currents and slow Ca2+ currents in the distal part of
      apical dendrites is highly sensitive to the dynamic state of the dendritic
      membrane. Depending on the mode and frequency of activation these currents can
      exert a substantial influence on the input-output behavior of the pyramidal
      neurons.

PMID- 8878747
TI  - Experimental Schistosoma bovis infection in goats: pathological consequences of
      praziquantel treatment.
AB  - Schistosoma bovis-infected goats were treated with praziquantel (60 mg/kg) and
      killed for examination 1, 7 or 28 days later. Infected non-treated goats and
      parasite-free, treated or non-treated goats were included for comparison. The
      gross pathological changes seen in the infected non-treated groups were mild to
      moderate. The liver appeared discoloured and moderately enlarged. The intestinal
      lesions were most prominent in the small intestines, which showed catarrhal
      inflammation with numerous tiny corpuscles beneath the luminal surface. The
      mesenteric lymph nodes were slightly to moderately enlarged. In contrast, on
      macroscopical examination, the infected treated groups invariably showed
      pronounced liver changes and marked enlargement of the lymph nodes, whereas the
      lesions in the intestines were comparatively slight. Histological lesions related
      to dead worms were seen in the livers of all treated animals. These lesions
      included pronounced inflammatory cellular infiltrates, thrombophlebitis, necrosis
      and periportal fibrosis, still severe 4 weeks after treatment. In the intestines,
      the deposition of new eggs with little cellular reaction had almost completely
      ceased 1 week after treatment. Four weeks after treatment, only a very few egg
      associated lesions were noted in the intestines. The presence of severe lesions
      attributable to dead worms in the liver indicates the need for caution when
      treating animals with high worm loads or concomitant liver disease.

PMID- 8878748
TI  - Gossypol toxicosis in the rat associated with protein malnutrition and
      experimental infection with Trypanosoma brucei.
AB  - The toxicity of gossypol, a compound occurring naturally in the cotton plant, was
      investigated in Trypanosoma brucei-infected, gossypol-treated rats, with and
      without protein malnutrition. The liver, heart, lungs, spleen and adrenal glands
      were enlarged in all gossypol-treated rats. Gossypol treatment or trypanosome
      infection, either alone or together, invariably caused significant reductions in
      the serum activity of creatine phosphokinase and amylase and in the serum
      concentration of cortisol. The serum biochemical changes, together with
      histopathological findings in various organs, indicated that the toxicity of
      gossypol and pathology of trypanosome infection, either alone or in concert,
      could be exacerbated by protein malnutrition. This finding suggests that the
      previously reported antiparasitic properties of gossypol may be of little
      ultimate benefit due to these serious side effects. The spleen in the protein
      malnourished, trypanosome-infected and gossypol-treated animals exhibited only a
      slight decrease in the number of lymphatic nodules, but a marked cellular
      depletion, especially of cortical tissue, was observed in the thymus. These
      observations would seem to justify further study of the immune status of
      trypanosome-infected, gossypol-treated animals.

PMID- 8878749
TI  - Congenital myopathy in Braunvieh x Brown Swiss calves.
AB  - A hitherto unknown skeletal muscle disorder is described in six Braunvieh x Brown
      Swiss calves. The animals showed rapidly progressing muscular weakness and became
      recumbent within 2 weeks of birth. Histological examination of skeletal muscle
      revealed a marked variation in muscle fibre size, internally placed nuclei,
      segmental loss of cross-striation with disorganization of myofibrils, and
      accumulation of nemaline rods. The most distinctive histological finding was
      intracytoplasmic, homogeneous, mostly crescent-shaped areas at the periphery of
      numerous muscle fibres. Electron microscopically, accumulations of tightly
      packed, parallel filamentous structures, about 20 nm in diameter, were detected
      in these areas. Enzyme histochemistry showed that all muscle fibre types were
      affected. Vimentin and dystrophin immunohistochemistry revealed normal antigen
      distribution within connective tissue components and at the periphery of each
      muscle fibre, respectively. The lesions could be readily distinguished from other
      neurological and neuromuscular disorders previously described in Braunvieh x
      Brown Swiss or American Brown Swiss Cattle. The disease appears to be a novel
      congenital myopathy in this breed, and a hereditary aetiology is suspected.

PMID- 8878750
TI  - Developed and resolving lesions in porcine proliferative enteropathy: possible
      pathogenetic mechanisms.
AB  - Proliferative enteropathy, caused by Lawsonia intracellularis, offers the
      opportunity to examine bacterial mechanisms that influence epithelial cell
      proliferation. Ultrastructural features of developed and resolving lesions
      included the presence of enlarged intestinal crypts containing undifferentiated
      immature epithelial cells and an absence of goblet cells. Numerous
      intracytoplasmic bacteria, identified as L. intracellularis, were consistently
      present within affected cells. In recovering intestinal tissue, additional
      features were (1) the common presence of pale, swollen, protruding epithelial
      cells, (2) shrunken, degenerate epithelial cells, (3) apoptotic bodies in both
      epithelial cells and macrophages, (4) the reappearance of normal goblet cells,
      and (5) reduced numbers of L. intracellularis within lesions. Bacteria were
      released from cells via cytoplasmic and cellular protrusions into the intestinal
      lumen. It is speculated that the presence of the intracytoplasmic bacterium, L.
      intracellularis, may disrupt normal processes of cell growth, differentiation or
      apoptosis in the intestinal epithelium.

PMID- 8878751
TI  - Effects of water pollution on the gill apparatus of fish.
AB  - The study was designed to investigate the influence of water pollution on gill
      apparatus. Specimens of Nile tilapia were collected from a polluted site in the
      Sao Paulo metropolitan area (Billings reservoir) and from a "clean" area. Fish
      from the polluted site showed a chronic inflammatory process in the distal region
      of the gill filaments, with epithelial hyperplasia. The raker length was
      increased and hypersecretion occurred, with a considerable volume of alcian blue
      positive mucin on the epithelium of the rakers and a smaller volume of periodic
      acid-Schiff-positive mucin on the epithelial surface of the filaments. The
      rigidity of mucus in fish from the polluted site was increased, but no
      abnormalities in the viscosity to elasticity ratio or in mucus "wettability" were
      observed.

PMID- 8878752
TI  - Structural and ultrastructural study of glomerular changes in African swine
      fever.
AB  - The pathological effect of haemorrhagic fever viruses on the kidney have not been
      clearly documented. This study reports glomerular lesions in African swine fever.
      In the acute form of the disease there was an acute diffuse proliferative
      glomerulonephritis, which was believed to be related to virus replication in
      circulating monocytes and glomerular mesangial cells, and to the presence of
      abundant circulating cell debris resulting from viral replication at other sites.
      In the subacute form, the proliferative mesangial glomerulonephritis observed may
      have been associated with systemic immune-mediated phenomena, and with
      subendothelial and mesangial deposits of immunoglobulins and complement
      components.

PMID- 8878753
TI  - Dysuria associated with urethral caruncle in the dog.
AB  - Three cases of urethral caruncle were recognized in bitches with a history of
      chronic dysuria. Clinical and radiological examinations revealed the presence of
      inoperable lesions involving much of the urethra in all three cases. At post
      mortem examination of Case 1, an oval swelling, 1.5 x 1.0 cm, was detected within
      the wall of the urethra close to the vagino-urethral orifice. In Case 2, firm,
      mottled yellow, white and red tissue formed a thickening between the urethra and
      vagina. In Case 3, a cylindrical cream mass, 8 cm long and 3 cm in diameter,
      surrounded the urethra and impinged on the wall of the vagina. Histologically,
      glandular structures lined by a single layer of epithelial cells and a mixed
      granulomatous inflammatory reaction were present in the wall of the urethra of
      all three cases.

PMID- 8878754
TI  - Congenital polyalveolar lobe in three foals.
AB  - Three cases of congenital polyalveolar lobe (pulmonary hamartoma) were diagnosed
      in female Thoroughbred foals. Foal 1 was born at full term but died shortly
      afterwards. Foal 2 was aborted at the seventh month of gestation. Parturition was
      induced at the tenth month of gestation in foal 3 because it developed hydrops of
      the amnion and ascites. In all three foals, the polyalveolar lobe occurred on the
      right side and affected the entire right lung. In each case, the right lung
      formed a tumour-like mass, and expanded into the left chest cavity. The lung
      masses were pink to dark red and spongy to rubbery, with marked lobular patterns
      on the pleural and cut surfaces. The left lung was compressed and small. The
      right and left lungs weighed 0.9-6.3 kg and 80 g-0.3 kg, respectively.
      Microscopically, the polyalveolar lobe consisted of normal alveoli, bronchioli
      and blood vessels, but the alveolus:artery ratio was greater than normal. In the
      polyalveolar lobe of two foals the numbers of alveoli per artery were 65.2 and
      52.5; in contrast, the corresponding values for three control lungs were 26.9,
      26.5 and 27.6. Chronic passive congestion with generalized oedema was observed in
      foals 2 and 3.

PMID- 8878755
TI  - Non-functional pituitary chromophobe adenoma in a calf.
AB  - A 5-month-old male calf showed neurological signs, including circling, in-co
      ordination, depression, blindness and eventual recumbency. On necropsy, a mass
      measuring 3.5 x 4.5 x 5 cm was found at the base of the brain, at the level of
      the pituitary gland. The hypothalamus and optic nerves were compressed by the
      dorsally expanding mass. Non-functional pituitary chromophobe adenoma was
      diagnosed from histochemical, immunohistochemical and electron microscopical
      findings.

PMID- 8878756
TI  - Acute myeloblastic leukaemia in a cow.
AB  - A myeloblastic leukaemia was found in a 6-year-old Holstein cow. Although
      macroscopical lesions were not found in parenchymal organs, the animal had many
      neoplastic cells in the peripheral blood, bone marrow, lymph nodes, and spleen.
      By light microscopy most neoplastic cells appeared to be agranular blast cells,
      but some cells contained acidophilic granules and stained positively for naphthol
      AS-D chloroacetate esterase and lysozyme. Ultrastructural examination revealed
      that many of the blast cells had a few peroxidase-positive granules and
      corresponded to early promyelocytes.

PMID- 8878757
TI  - Improvement in quality of life in patients with heart failure who undergo
      transplantation.
AB  - BACKGROUND: Very few studies have examined quality of life longitudinally in
      heart failure patients from before or after heart transplantation. The purpose of
      this study was to compare quality of life of patients with heart failure at the
      time of listing for a heart transplant with that 1 year after the operation.
      Major dimensions of quality of life measured in this study were health, physical
      and emotional functioning, and psychosocial functioning. METHODS: A convenience
      sample of 148 patients (80% male and mean age 52 years) was recruited from a
      midwestern and southern medical center. Data were collected from chart review and
      six patient-completed instruments: the Heart Transplant Symptom Checklist,
      Sickness Impact Profile, Heart Transplant Stressor Scale, Jalowiec Coping Scale,
      Quality of Life Index, and Rating Question Form. Informed consent was obtained,
      and patients who agreed to participate in the study completed the booklet of self
      administered instruments. Statistical analyses included frequencies, measures of
      central tendency, paired t-tests, and Wilcoxon signed-ranks tests. RESULTS: Total
      symptom distress decreased significantly overall from before to after heart
      transplantation (before = 0.19 versus after = 0.15, p < 0.0001). Patients rated
      themselves as having significantly poorer health while listed as a heart
      transplant candidate than at 1 year after surgery (before = 4.5 versus after =
      7.5, p < 0.0001). Although the overall level of functional disability was fairly
      low before and 1 year after transplantation, patients still reported significant
      improvement after surgery (before = 0.21 versus 1 year after = 0.13, p < 0.0001).
      No significant differences were found in total stress, which was low to moderate
      (before = .026 versus 1 year after = 0.26, p = not significant), coping use
      (before = 0.48 versus 1 year after = 0.48, p = not significant), or coping
      effectiveness (before = 0.40) versus 1 year after = 0.42, p = not significant),
      from before to 1 year after heart transplantation. However, changes in types of
      symptoms, functional disability, stressors, and coping were noted over time.
      Overall satisfaction with life, which was fairly high at both time periods,
      increased significantly from the time of listing for a transplant to 1 year after
      surgery (before = 0.72 versus 1 year after = 0.82, p <0.0001), and overall
      quality of life improved significantly from before to after heart transplantation
      (before = 5.5 versus after = 7.8, p < 0.0001). CONCLUSIONS: End-stage heart
      failure patients had improved quality of life from before to 1 year after heart
      transplant due to less total symptom distress, better health perception, better
      overall functional status, more overall satisfaction with life, and improved
      overall quality of life. However, post-transplant patients still experienced some
      symptom distress, functional disability, and stress, but were coping well.

PMID- 8878758
TI  - Pneumocystis carinii pneumonia in infants after heart transplantation.
AB  - Although the reported incidence of Pneumocystis carinii pneumonia after heart
      transplantation in adults ranges from 3% to 40%, data are lacking regarding the
      incidence in the pediatric heart transplantation population. A retrospective
      review was performed on 152 infants (0 to 12 months of age) undergoing
      transplantation from November 1985 through December 1993 who survived at least 6
      months after heart transplantation. Patients did not receive postoperative
      Pneumocystis carinii prophylaxis. Ten episodes (7%) were diagnosed in four
      neonates and six infants. The mean postoperative time to Pneumocystis carinii
      diagnosis was 5 months (range 3 to 9 months). Features of Pneumocystis carinii
      included hypoxia and tachypnea (10 of 10), progressive interstitial infiltrates
      (8 of 10), and persistent right middle lobe consolidation (1 of 10). Pneumocystis
      carinii was diagnosed with the use of bronchoscopy in eight cases and by open
      lung biopsy in two cases. Mean CD4 count available on five patients at the time
      of Pneumocystis carinii diagnosis was 413/mm3 (range 158 to 1358); 5 of 37
      patients receiving antithymocyte induction had Pneumocystis carinii versus 5 of
      115 patients who did not receive induction (p = 0.05). Patients were at increased
      risk for the development of Pneumocystis carinii if they had more than two
      episodes of rejection during the first year after heart transplantation (p =
      0.04). All cases were successfully treated with trimethoprim/sulfamethoxazole.
      The incidence of Pneumocystis carinii in infant heart transplantation recipients
      is approximately 7% and appears most frequently in the first 6 months after the
      operation. Increased risk for Pneumocystis carinii may be related to early
      antithymocyte induction and increased episodes of rejection.

PMID- 8878759
TI  - The combined effects of brain death and cardiac graft preservation on
      cardiopulmonary hemodynamics and function before and after subsequent heart
      transplantation.
AB  - BACKGROUND: The combined effects of brain death and graft preservation on right
      and left ventricular function and on pulmonary hemodynamics after subsequent
      heart transplantation have not been previously studied. METHODS: Fifty-seven dogs
      (25.5 +/- 0.3 kg) were divided into three groups and underwent a total of 20
      brain death experiments and 16 orthotopic complete atrioventricular
      transplantations with the use of a validated brain death organ donor model,
      hypothermic heart preservation, and right and left ventricular functional
      analysis (preload-independent recruitable stroke work, Fourier analysis). In the
      first group, changes in cardiopulmonary function were assessed over a period of 6
      to 7 hours after brain death. In the second group, the hearts were procured from
      a donor with brain death and immediately transplanted whereas in the third group
      cardiac graft preservation for a period of 4 hours followed harvest from a donor
      with brain death before heart transplantation and assessment of heart transplant
      function. RESULTS: After brain death alone, a significant increase in right and
      left ventricular end-diastolic pressures and a decrease in systemic and pulmonary
      resistance and pulmonary impedance occurred. Furthermore, right and left
      ventricular function decreased significantly by 35% and 19%, respectively, and
      subsequent transplantation did not cause further cardiac dysfunction.
      Preservation in combination with brain death led to further significant decreases
      in right ventricular function after subsequent transplantation compared with
      brain death alone, necessitating the use of dopamine to wean four animals from
      cardiopulmonary bypass. CONCLUSION: Brain death causes a significant loss of
      right and left ventricular function. These injuries are greater in the right
      ventricle and may contribute to early right ventricular failure after
      transplantation. Brain death and cardiac graft preservation have significantly
      additive deleterious effects on right ventricular function after transplantation.

PMID- 8878760
TI  - Experimental and clinical allogeneic heart transplant rejection: correlations
      between histology and immune reactivity detected by cytokine messenger RNA.
AB  - BACKGROUND: Cytokines produced by host cells infiltrating allogeneic transplants
      are critical determinants of graft rejection but information on cytokine
      production during graft rejection remains limited. No reported study on cytokine
      profiles has compared experimental allograft rejection induced by withdrawal of
      cyclosporine with clinical transplant rejection that occurs in the presence of
      therapeutic levels of cyclosporine. METHODS: Functional activities of allograft
      infiltrating host cells in sequential endomyocardial biopsies obtained before,
      during, and after acute heart transplant rejection were determined with the use
      of the reverse transcriptase-polymerase chain reaction to detect cytokine
      messenger RNA. These results were correlated with histologic findings in both an
      experimental canine model of heart transplant and rejection and in clinical human
      heart transplant recipients. RESULTS: When experimental rejection was induced by
      withdrawal of immunosuppression, rejection was characterized by the presence of
      mRNA encoding CD4, CD8, interleukin-2 (but not interleukin-4), interleukin-2
      receptor, and tumor necrosis factor-beta. These findings are consistent with a
      classic T-helper, T-cytotoxic cell-mediated response. However, the cytokine
      profile of human, clinical heart transplant rejection occurring in the presence
      of therapeutic levels of immunosuppression differed strikingly. In clinical
      rejection in human beings, histologic evidence of rejection was not associated
      with detectable interleukin-2 or interleukin-2 receptor mRNA. CONCLUSIONS: Human,
      clinical heart rejection can occur in the absence of locally produced interleukin
      2; the degree of immunosuppression achieved with cyclosporine A may explain the
      different results obtained in the canine withdrawal model versus human clinical
      allograft rejection.

PMID- 8878761
TI  - Effect of single-dose rapamycin-based immunosuppression on the development of
      cardiac allograft vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy is the major cause of graft loss more
      than 1 year after transplantation. Daily rapamycin dosing has been shown to
      inhibit arterial intimal thickening caused by both alloimmune and mechanical
      injury. The combination of a single preoperative dose of rapamycin with a short
      (7 day) course of cyclosporine A has been shown to extend cardiac allograft
      survival, but its effects on the development of cardiac allograft vasculopathy
      has not been reported. METHODS: The ACI (RT1(a)) to Lewis (RT1(1)) heterotopic
      cardiac allograft model was used to assess the development of cardiac allograft
      vasculopathy and rejection. Treatment groups included nonimmunosuppressed
      control, cyclosporine A, cyclosporine A/donor-specific transfusion, and
      rapamycin/cyclosporine A. RESULTS: The addition of a single preoperative dose of
      rapamycin to a short course of cyclosporine A significantly reduced the
      prevalence of cardiac allograft vasculopathy in small (1.18 +/- 1.4 versus 0.05
      +/- 0.3; p = 0.0001), medium (2.05 +/- 1.09 versus 0.26 +/- 0.62; p = 0.0001),
      and large (2.57 +/- 0.84 versus 1.43 +/- 1.2; p = 0.0008) vessels when compared
      with that in allografts treated with a single preoperative donor-specific
      transfusion and the same cyclosporine A schedule. Cardiac allograft vasculopathy
      did not develop in the nonimmunosuppressed control grafts or the group treated
      with cyclosporine A alone, because of the short survival times in these groups.
      In addition, there was a reduction of the rejection score in the rapamycin
      treated allografts compared with that in the other treatment groups (4.0 +/- 0.0
      versus 3.25 +/- 0.5; p = 0.0006). CONCLUSIONS: These results suggest that a
      single preoperative dose of rapamycin is efficacious in preventing the
      development of cardiac allograft vasculopathy, and continued immunosuppression
      with rapamycin may be unnecessary.

PMID- 8878762
TI  - Influence of acute or chronic rejection on myocardial collagen density in serial
      endomyocardial biopsy specimens from cardiac allografts.
AB  - BACKGROUND: The knowledge of long-term changes in the transplanted heart is still
      incomplete. Among these changes that could potentially have an adverse effect on
      long-term cardiac function, myocardial fibrosis is of great concern. The aim of
      this study was to investigate the possible influence of acute or chronic
      rejection on the development of myocardial fibrosis in cardiac allografts.
      METHODS: We used light microscopic computer-assisted morphometry of collagen
      density in 200 right ventricular endomyocardial biopsy specimens taken routinely
      in 21 heart transplant recipients during a mean follow-up period of 36 months
      (range, 12 to 84). The 21 patients were divided into two groups according to the
      presence of chronic rejection assessed by coronary angiography. The first group
      consisted of 11 patients with no chronic rejection; the second group consisted of
      10 patients with chronic rejection. Both groups were divided into four subgroups
      according to the highest grade of acute rejection reached during the follow-up
      period (subgroup 1, no acute rejection or grade 1A; subgroup 2, grade 1B;
      subgroup 3, grades 3A or 3B; subgroup 4, grade 4). Patients of both groups were
      selected on the basis of similarity patterns in clinical characteristics and mean
      follow-up time. RESULTS: Patients with no chronic rejection had relatively little
      variation in serial determinations of myocardial collagen density. During the
      prechronic and chronic phases in patients with chronic rejection, we found no
      overall increase in myocardial collagen density. In both the chronic rejection
      and no chronic rejection groups there was no consistent relationship between
      myocardial collagen density and severity of acute rejection. In both groups there
      were occasional strikingly elevated myocardial collagen density values that were
      well above the other serial determinations. These elevated values of collagen
      density were mainly a result of scars, the sequellae of prior myocyte damage,
      because neither interstitial nor perivascular fibrosis could be detected.
      CONCLUSION: During this long-term follow-up study of endomyocardial biopsy
      samples, we found no significant association between either acute or chronic
      rejection and the later increase in myocardial collagen density.

PMID- 8878763
TI  - A histopathologic grading system of hyperacute (humoral, antibody-mediated)
      cardiac xenograft and allograft rejection.
AB  - BACKGROUND: If future attempts to introduce xenografting into clinical practice
      prove successful, it will be essential to have a clinically relevant,
      reproducible grading system for vascular rejection. No formal attempt has been
      made to grade hyperacute or delayed vascular rejection on the basis of a review
      of both experimental and clinical material. METHODS AND RESULTS: In an attempt to
      define a microscopic grading system for hyperacute vascular rejection of the
      heart, we reviewed the clinical and histologic findings in 112 previously
      personally studied experimental (n = 109) and clinical (n = 3) cardiac xenografts
      and allografts, most of which showed vascular rejection. The study material
      comprised 44 discordant xenografts, 41 concordant xenografts, and 27 allografts.
      We documented, analyzed, and grouped the histopathologic features together with
      the clinical data. We devised a grading system which allowed us to allocate each
      sample to one of the following two categories: grade A: unmodified hyperacute
      rejection; grade B: mixed hyperacute and acute cellular rejection. Both grades A
      and B can be subcategorized into three stages: (1) mild (initial), (2) moderate
      (intermediate), or (3) severe (late) stage. CONCLUSIONS: A common grading system
      can be applied to both hyperacute rejection and mixed (hyperacute and acute)
      rejection. The proposed grading system provides a basis for meaningful pathologic
      evaluation of hyperacute rejection.

PMID- 8878764
TI  - Morphometric and immunocytochemical analysis of coronary arterioles in human
      transplanted hearts.
AB  - BACKGROUND: Heart transplant vascular sclerosis has been characterized in
      epicardial coronaries of human transplanted hearts. The purpose of this study was
      to analyze coronary arterioles (< 100 microns in diameter) within endomyocardial
      biopsy specimens from heart transplant recipients for the presence of disease.
      METHODS: The morphologic compartments of trichrome-stained vessels were
      quantified by means of computer imaging to measure the percentage of stenosis of
      164 arterioles from 30 transplant recipients over time. The arterioles were
      divided into three groups based on their biopsy date after transplantation: early
      (0 to 6 months), middle (6 to 18 months), and late (18 to 36 months). The
      percentage of stenosis of arterioles from a control group of nondiseased hearts
      was compared with the grafts. Also, arterioles from heart transplant recipients
      were immunohistochemically labeled with an antibody, PC10, specific for
      proliferating cell nuclear antigen. The arterioles were immunocytochemically
      labeled with an antibody specific for vascular smooth muscle alpha-actin and the
      fluorescent signal was analyzed. RESULTS: The percentage of stenosis was not
      significantly different among the early, middle, late, and control groups.
      Vessels from the early, middle, and late groups did not show binding of the PCNA
      antibody. The antibody signal intensity and amount of alpha-actin within each
      vessel was significantly higher in the late groups as compared with the early and
      middle groups. CONCLUSIONS: The coronary microvasculature of human transplanted
      hearts does not exhibit intimal thickening or cellular proliferation within 3
      years after transplantation. However, as shown by an increase of smooth muscle
      alpha-actin over time, vascular remodeling may occur in response to cytokines
      released as a result of injury.

PMID- 8878765
TI  - Mycotic aortic aneurysms after orthotopic heart transplantation: a three-case
      report and review of the literature.
AB  - Mycotic aortic aneurysm is a rare yet life-threatening complication after
      orthotopic heart transplantation. This article reviews three cases of mycotic
      aortic aneurysm in heart transplant recipients developing in the first year after
      heart transplantation. Excision of the aneurysm and in situ reconstruction of the
      ascending aorta were performed with a patch of glutaraldehyde-fixed pericardium
      or cryopreserved aortic allograft material as a patch or conduit replacement.
      These cases show that early diagnosis by computed tomographic scanning, surgical
      treatment, high-dose parenteral antibiotics, and close follow-up are essential
      for successful treatment.

PMID- 8878766
TI  - Transient aplastic anemia caused by parvovirus B19 infection in a heart
      transplant recipient.
AB  - Parvovirus B19 infection in the transplant patient is rarely reported, although
      cases have occurred in patients with bone marrow, liver, and renal transplants
      and in children undergoing heart transplantation. We present the first reported
      case of an orthotopic heart transplant recipient with aplastic crisis caused by
      parvovirus B19. The infection was diagnosed by bone marrow biopsy, confirmed by
      serologic studies and polymerase chain reaction, and successfully treated with
      intravenous immunoglobulin.

PMID- 8878767
TI  - Pseudopericardial effusions in heart transplant recipients.
AB  - BACKGROUND: The objective of this study was to determine the nature of
      sonographically observed band-shaped, homogeneous, almost echo-free structures
      located ventral to the right ventricle of the heart in heart transplant
      recipients. METHODS: A total of 212 consecutive heart transplant recipients was
      evaluated sonographically. RESULTS: In 18 of the 212 patients (8.5%) band-shaped
      structures were detected, and these structures were proved with computed
      tomography or magnetic resonance imaging to be caused by mediastinal fat.
      CONCLUSIONS: A sonographically demonstrable, almost echo-free band-shaped
      structure located ventral to the heart should not be misinterpreted as localized
      pericardial effusion.

PMID- 8878768
TI  - Severe hemolysis caused by graft-derived anti-B production after lung
      transplantation.
AB  - Anti-B antibody causing sever hemolytic anemia and renal failure was found in the
      serum of a blood group B patient who had received a bilateral lung transplant
      from a blood group O donor. Although the donor origin of the antibody was not
      confirmed, it is likely that the anti-B antibody was produced by donor passenger
      B lymphocytes.

PMID- 8878769
TI  - Eosinophilic myocarditis in heart transplant candidates.

PMID- 8878770
TI  - Cell-mediated responses to donor endothelium: reinterpretation of the data.

PMID- 8878771
TI  - Intrafamily transmission of hepatitis C virus: sexual and non-sexual contacts.
AB  - BACKGROUND/METHODS: As a high number of patients with antibodies to hepatitis C
      (anti-HCV) do not have a known history of parenteral acquisition, other non
      parenteral means of hepatitis C virus transmission must be studied. We
      investigated 1451 household contacts of 535 anti-HCV positive, human
      immunodeficiency virus-negative index patients. RESULTS: Overall, the prevalence
      of anti-HCV in household contacts was 4.5%. Thirty (7.6%) out of the 394
      heterosexual stable partners were anti-HCV positive as compared to 35 (3.3%) out
      of 1057 non-sexual contacts (p < 0.01). The prevalence of anti-HCV was lowest in
      children of the index cases (1.8%). In this group, the prevalence of anti-HCV was
      3% (10/330) when the mother was the index case, as opposed to 0.6% (2/328) when
      the father was the index case (p < 0.05). The prevalence of anti-HCV increased
      with age, being highest (18.6%) in family contacts older than 60 years.
      CONCLUSIONS: Transmission of hepatitis C virus may occur among household contacts
      of anti-HCV positive patients. Sexual contact or the use of non-disposable
      medical material in the past might explain the higher prevalence of anti-HCV
      found in sexual partners and in family contacts older than 60 years of age. Anti
      HCV screening should be performed in family contacts of anti-HCV positive
      patients, particularly in those contacts older than 20.

PMID- 8878772
TI  - Quality of life, major medical complications and hospital service utilization in
      patients with primary biliary cirrhosis after liver transplantation.
AB  - AIMS/METHODS: Major medical complications, hospital service utilization and
      quality of life were investigated in 26 out of 29 consecutive primary biliary
      cirrhosis transplanted patients who survived at least 2 years after the procedure
      (90% survival rate). RESULTS: Before liver transplant, the most relevant clinical
      data were jaundice (96%), pruritus (92%), ascites (50%), gastrointestinal
      bleeding (19%), hepatic encephalopathy (12%) and bone pain (12%). During the
      first postoperative year, the most significant complications were bone pain (58%)
      and fractures (31%), arterial hypertension (50%), and mild/moderate renal failure
      (46%). The frequency of these complications remained similar during the second
      year, but there was a significant reduction in the incidence of bone fractures.
      Bone pain was the only postoperative complication which correlated with an
      increased number of unscheduled outpatient and emergency visits. Quality of life
      was measured cross-sectionally either at or after the second postoperative year.
      The Karnofsky index was 90 in 69% of the patients and 76% were able to perform
      usual daily activities. Self-assessed health perception was good or very good in
      almost all the patients. However, the Nottingham Health Profile showed that
      approximately 70% of the patients gave a positive response to some questions in
      areas of pain, sleep, emotional reactions and physical activities. CONCLUSIONS:
      The results of the present study confirm that patients with primary biliary
      cirrhosis have a high survival rate after liver transplantation and that bone
      pain and fractures are important postoperative complications. Good self-perceived
      health and return to daily activities evidenced in most PBC patients should be
      balanced with problems identified by more specific tools, which could have an
      impact on the health service utilization and quality of life.

PMID- 8878773
TI  - Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in
      patients with cirrhosis and refractory ascites: a randomized trial. French Group
      of Clinicians and a Group of Biologists.
AB  - BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunts reduce portal
      pressure and can control ascites in patients with cirrhosis. We carried out a
      controlled study to evaluate this procedure for the management of refractory
      ascites in patients with cirrhosis and to clarify its mechanism of action.
      METHODS: Twenty-five patients with refractory ascites were included in the trial;
      13 were randomly assigned to shunts and 12 to paracentesis. Four patients in each
      group were Child-Pugh class C and the others were class B. Follow-up ranged from
      9 to 34 months. Hemodynamic values, liver and renal tests and neurohumoral
      factors were measured before and at 4 months after inclusion. RESULTS: Shunts
      were successfully placed in 10 out of 13 patients. At 4 months, ascites had
      improved in all class B patients in the shunt group and in none of the patients
      in the paracentesis group (p < 0.05); ascites did not improve in any of the class
      C patients in either of the groups. At 2 years, the overall survival rate was 29
      +/- 13% (mean +/- SE) in the shunt group and 56 +/- 17% in the paracentesis group
      (p < 0.05). In class B patients, there was no significant difference in
      mortality. At 4 months, portal pressure was significantly lower than before the
      shunt, while plasma levels of atrial natriuretic peptide were significantly
      higher and plasma levels of renin and norepinephrine significantly lower.
      CONCLUSIONS: In this trial, intrahepatic shunts were effective on refractory
      ascites in patients with cirrhosis. However, the overall survival rate was lower
      in shunted patients than in those treated with paracentesis. The efficacy of
      intrahepatic shunts on ascites was only observed in class B patients. Survival
      did not improve in class B patients, and decreased in class C patients compared
      to paracentesis. The efficacy of shunts on ascites might be due to neurohumoral
      factors which control natriuresis and depend on hepatic sinusoidal pressure.

PMID- 8878774
TI  - Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of
      gradual cerebral hyperaemia.
AB  - BACKGROUND/AIMS: Normally, cerebral blood flow responds to changes in the
      arterial carbon dioxide tension (PaCO2) but not to changes in mean arterial
      pressure, commonly referred to as the cerebral CO2-reactivity and autoregulation.
      In patients with fulminant hepatic failure and in the rat with thioacetamide
      induced liver failure, autoregulation is absent, presumably due to cerebral
      vasoparalysis. Since also CO2-reactivity may then be compromised, it was studied
      in patients with fulminant hepatic failure and rats with thioacetamide-induced
      liver failure. METHODS: In ten patients (median age 32 (range 20-48) years)) and
      in ten age-matched volunteers, cerebral perfusion was elevated by transcranial
      Doppler assessed mean flow velocity (V(mean)) in the middle cerebral artery
      during hypo- and hyper-capnia. In six rats with liver failure and in six control
      rats, cerebral blood flow was measured repeatedly by the intracarotid 133 Xenon
      injection technique. RESULTS: In the patients and volunteers, PaCO2 was lowered
      from 33 (23-44) to 28 (23-39) mmHg by hypocapnia and raised to 40 (34-48) mmHg by
      hypercapnia or 5% CO2 inhalation. During hypocapnia, the CO2-reactivity did not
      differ significantly between patients and volunteers, 4.0 (1.1-7.4) vs. 3.0 (1.7
      5.0)% mmHg(-1), while it was reduced during hypercapnia in the patients, 2.2 (1.8
      5.2) vs. 4.6 (3.0-8.0)% mmHg(-1) (p < 0.05). In the rats, PaCO2 was reduced from
      39 (37-40) to 30 (29-31) mmHg and then raised to 51 (41-55) mmHg. During
      hypocapnia, CO2-reactivity was similar in rats with liver failure and in control
      rats, 2.3 vs 2.7% mmhg(21), respectively. In all rats with liver failure CO2
      reactivity was abolished during hypercapnia, while it was 1.5% mmHg(-1) in the
      control rats (p < 0.01). CONCLUSIONS: The finding that cerebral CO2 reactivity is
      reduced in hypercapnia, while it is preserved in hypocapnia, suggests that
      gradual dilation of the cerebral resistance vessels develops in fulminant hepatic
      failure and connects previous morphological studies with changes in the
      regulation of cerebral blood flow, i.e. impaired cerebral autoregulation and
      blunted CO2-reactivity.

PMID- 8878775
TI  - Evaluation of 24-hour gastric acidity in patients with hepatic cirrhosis.
AB  - BACKGROUND/AIMS: Data from previous studies on gastric acid secretion in patients
      with hepatic cirrhosis are controversial, due, at least in part, to the possible
      interference of liver failure and altered gastric mucosal microcirculation on the
      pharmacological action of the substances used to stimulate the parietal cell. For
      this reason, we wished to investigate the circadian pattern of gastric acidity by
      means of continuous 24-hour pH monitoring, which permits measurement of pH
      fluctuations in a nearly physiological manner and does not require any
      pharmacological stimulus. METHODS: Forty-nine patients with liver cirrhosis of
      different aetiology were recruited for this study. They underwent 24-hour gastric
      pH-metry with an electrode positioned in the gastric corpus, and their pattern of
      gastric acidity was compared with that of 49 healthy subjects, matched for age
      and sex. In a subgroup of 31 patients with cirrhosis, antral pH was recorded in
      addition to body pH in order to assess whether there are regional differences in
      gastric acidity. RESULTS: The circadian, daytime and nocturnal gastric acidity in
      patients with cirrhosis was significantly lower (p < 0.05-0.001) than that of
      controls. In the 31 patients studied with two electrodes, antral pH was higher (p
      < 0.05) than body pH only during the night. The prevalence of Helicobacter pylori
      infection was rather low (42%) in our patients. CONCLUSIONS: There is a marked
      hypoacidity over the circadian cycle in patients with cirrhosis compared to
      controls, and the greatest difference between them is visible during the
      nocturnal hours. Also, in patients with liver cirrhosis the pH in the antrum is
      higher than that in the body of the stomach during the night for reasons that
      need to be elucidated.

PMID- 8878776
TI  - Characterisation of the DNA repair enzyme for O(6)-methylguanine in cirrhosis.
AB  - BACKGROUND/AIMS: The reason(s) why cirrhosis is a major risk factor for the
      development of hepatocellular carcinoma worldwide are largely unknown. In a
      previous preliminary study, we reported deficiency of the repair enzyme for the
      highly promutagenic and potentially carcinogenic DNA base lesion, O(6)
      methylguanine, in cirrhotic human liver. The aims of the present study were: (i)
      to confirm this observation in an extended series of cirrhosis patients, using a
      new DNA repair enzyme assay approach, (ii) to characterise the enzyme, in
      particular to seek physicochemical differences between control and cirrhotic
      liver that might account for the enzyme defect in cirrhosis, and (iii) to examine
      the relationship between magnitude of DNA repair deficiency in cirrhotic liver
      and aetiology of cirrhosis or male sex, both of which are independent risk
      factors of hepatocellular carcinoma. METHODS: Tissue extracts containing DNA
      repair enzyme, O(6)-methylguanine-DNA methyltransferase, were prepared from liver
      biopsy samples from 41 patients with cirrhosis (10 viral (HBV and HCV), 17
      alcohol and 14 autoimmune), 17 patients with non-cirrhotic diseased liver and 4
      patients with histologically normal liver. Repair enzyme levels and
      electrophoretic profiles were both obtained using sodium dodecyl sulphate
      polyacrylamide gel electrophoresis in conjunction with fluorography and
      densitometry. RESULTS: We have demonstrated the feasibility of both analysing and
      reproducibly measuring DNA repair enzyme in small liver biopsy samples using the
      gel electrophoresis/densitometry approach for enzyme assay. Using the new
      densitometric assay approach, levels of O(6)-methylguanine-DNA methyltransferase
      were found to be significantly lower in cirrhotic compared to non-cirrhotic
      liver, with very low values obtained for two individuals who were incidentally
      found to have small hepatocellular carcinomas at the time of liver
      transplantation. There were no significant differences in enzyme levels between
      patients with cirrhosis of different aetiology, and between male and female
      patients. Methyltransferase was found to be present in all liver extracts as a
      major 23.1 kDA protein, along with other less abundant enzyme forms of both
      slightly higher and lower molecular weight; there were no obvious differences in
      size and relative abundance of these enzyme forms between liver samples from any
      of the patient and control groups. Our findings of enzyme instability and
      multiple forms led us to examine methyltransferase's amino acid sequence for the
      presence of primary structure motifs indicative of targeted degradation of the
      enzyme by intracellular proteases. We have identified a eukaryotic thiol protease
      active site motif and two cyclin-like "destruction box" motifs in the N-terminal
      half of the enzyme. CONCLUSIONS: Our findings provide further evidence suggesting
      that deficiency in the ability to repair O(6)-methylguanine-DNA underlies the
      increased risk of hepatocellular carcinoma seen in patients with cirrhosis. The
      degree of DNA repair deficiency not varying between cirrhotic patients subgrouped
      according to other risk factors for hepatocellular carcinoma, suggests that DNA
      repair deficiency is only one of several contributory factors in liver
      carcinogenesis. The presence in methyltransferase of thiol protease active site
      and "destruction box" motifs may be of relevance to observed repair enzyme
      instability and presence of multiple enzyme forms in human liver extracts.

PMID- 8878777
TI  - Utility of lentil lectin affinity of alpha-fetoprotein in the diagnosis of
      hepatocellular carcinoma.
AB  - AIMS/METHODS: Frozen sera obtained from 70 patients (35 with hepatocellular
      carcinoma and 35 with benign chronic liver disease) with serum alpha-fetoprotein
      > 20 ng/ml were studied to evaluate the diagnostic indices of lentil lectin
      affinity of alpha-fetoprotein in detecting hepatocellular carcinoma. RESULTS: The
      proportion of alpha-fetoprotein-L3 was significantly higher in patients with
      hepatocellular carcinoma than in those with benign chronic liver disease (41.0 +/
      33.6% vs. 16.4 +/- 15.3%, p < 0.001). This difference led to a sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      57, 89, 83, 67 and 73%, respectively, in detecting hepatocellular carcinoma using
      the proportion of alpha-fetoprotein-L3 > 35% as a parameter. Within a 1-year
      period, 1500 high-risk persons were collaborating, leading to 22 cases with serum
      total alpha-fetoprotein > 20 ng/ml. These 22 cases included six pregnant women.
      The parameter, alpha-fetoprotein-L3 > 35% was used along with sonography to
      detect hepatocellular carcinoma for the remaining 16 cases. The sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy
      were 75, 83, 60, 91 and 81%, respectively, by the proportion of alpha-fetoprotein
      L3 > 35%; and 100, 92, 80, 100 and 94%, respectively, by sonography. CONCLUSIONS:
      Lentil lectin affinity of alpha-fetoprotein provides a moderately high
      sensitivity and a high specificity in the detection of hepatocellular carcinoma
      for persons with high alpha-fetoprotein levels. It may be a useful adjuvant tool
      of sonography and total alpha-fetoprotein level in a mass survey of
      hepatocellular carcinoma for a high-risk population.

PMID- 8878778
TI  - Variability in hepatic iron concentration measurement from needle-biopsy
      specimens.
AB  - BACKGROUND/AIM: Quantitative measurement of hepatic iron by biochemical analysis
      of liver biopsy samples is required to assess hepatic iron stores accurately.
      Cirrhotic livers, however, contain variable amounts of fibrous tissue and the
      distribution of iron within the hepatic parenchyma is not always uniform. The aim
      of this study was to assess the variability in hepatic iron concentration
      measurement from needle-biopsy specimens. METHODS: The livers from eight patients
      with cirrhosis selected because of elevated serum ferritin were obtained at the
      time of liver transplantation (n = 6) or at autopsy (n = 2). Multiple needle
      biopsies were done, and hepatic iron concentration was measured by atomic
      absorption spectroscopy. The hepatic iron index was calculated as iron
      concentration divided by age. RESULTS: Four cases had a mean hepatic iron index
      above 2.0, in the range of that reported in patients with homozygous genetic
      hemochromatosis, whereas the other four had an hepatic iron index of less than
      2.0. The intra-individual coefficient of variation for hepatic iron concentration
      ranged from 11.3 to 43.7%, averaging 24.9%. The coefficient of variation was
      smaller in biopsy samples > 4 mg dry weight than in samples < 4 mg (19.8% vs
      28.6%, p < 0.05). Histological examination of surgical biopsies from these livers
      showed large amounts of fibrous tissue, and inhomogeneous distribution or iron in
      the hepatic parenchyma. CONCLUSIONS: This study demonstrates an important
      variability in the measurement of hepatic iron content from needle biopsy
      specimens in patients with severe cirrhosis.

PMID- 8878779
TI  - Hepatocellular sulfobromophthalein uptake at physiologic albumin concentrations:
      kinetic evidence for a high affinity/low capacity sinusoidal membrane system.
AB  - BACKGROUND/AIMS: Controversy exists regarding the nature of the hepatocyte
      membrane transport system for sulfobromophthalein and other organic anions and
      its driving forces. Most studies have been performed in the absence of albumin,
      the plasma sulfobromophthalein binding protein, or using very low albumin
      concentrations. We have shown that in the latter case uptake kinetics reflect
      dissociation/diffusion events and not membrane transport. In contrast, without
      albumin very high sulfobromophthalein concentrations reach the cell surface and
      may overwhelm a high affinity/low capacity system operating in vivo. The aim of
      this study was to test the latter hypothesis. METHODS: Sulfobromophthalein uptake
      was measured by rapid filtration in isolated hepatocytes without albumin (up to
      13 microM sulfobromophthalein) and with 600 microM albumin
      (sulfobromophthalein:albumin from 0.03:1 to 1:1), a physiologic setting which
      greatly reduces the unbound BSP concentration. Unbound sulfobromophthalein
      concentration was estimated according to a three binding site model. RESULTS: In
      the absence of albumin, kinetic parameters for sulfobromophthalein uptake were
      similar to those reported in the literature (K(m):7.1 +/- 1.2 microM; V(max): 452
      +/- 37 pmol/min/5 x 10(4) cells). In the presence of albumin, sulfobromophthalein
      uptake displayed much greater affinity and much lower capacity (K(m): 80 +/- 11
      nM; V(max): 60 +/- 9 pmol/min/5 x 10(4) cells). CONCLUSIONS: These findings
      suggest that in the absence of albumin, resulting high sulfobromophthalein
      concentrations overload (and make undetectable) a high affinity/low capacity
      system operating at physiologic albumin concentrations (i.e. at low unbound
      sulfobromophthalein concentrations). Previously characterized transport systems
      may be operating only under defined conditions. These findings could explain the
      apparent controversy regarding the nature of the sulfobromophthalein transport
      system and its driving forces.

PMID- 8878780
TI  - Expression of liver-specific functions in rat hepatocytes following sublethal and
      lethal acetaminophen poisoning.
AB  - AIM: In order to study the short-term effect of moderate and severe reduction of
      liver function by acetaminophen poisoning of different severity on gene
      expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg
      body weight acetaminophen intragastrically. The lower dose is associated with low
      mortality; after the higher dose, most rats die at between 12 and 24 h. METHODS:
      In the morning, 1 1/2, 3, 6, 9, and 12 h after the injection, the rats were
      killed and RNA was extracted from liver tissue. By slot-blot hybridization mRNA
      steady-state levels were determined for enzymes involved in metabolic liver
      functions, i.e. ureagenesis, gluconeogenesis, and drug metabolism, for acute
      phase proteins, "house-keeping" proteins, and for proteins related to liver
      regeneration. Results were expressed as per cent of the level in similarly
      fasted, untreated rats of the same stock RESULTS: After the smaller dose of
      acetaminophen, most of the examined mRNA levels were increasing during the
      experimental period, being two- to four-fold elevated in relation to control
      after 6 to 12 h. Rats receiving the lethal dose either showed no or a later and
      smaller increase, and in several cases a fall towards the end of the experiment.
      The greatest differences were seen for mRNA of arginase, beta-fibrinogen, alpha 1
      acid glycoprotein, alpha-tubulin, histone 3, TGF beta, and cyclin d, i.e.
      proteins associated with acute phase response and liver cell replication and
      maintenance. CONCLUSIONS: It is concluded that reversible intoxication with
      acetaminophen induces an adaptive modulation of mRNA expression of liver
      functions and regeneration which is lacking after severe intoxication. This
      adaptation, with emphasis on acute phase response and regeneration, may be
      crucial for recovery after acetaminophen intoxication. If this also applies to
      the intoxication in man, estimates of the corresponding variables may be clues to
      the prognosis of acetaminophen-induced fulminant hepatic failure.

PMID- 8878781
TI  - Role of rate-limiting enzymes of nucleotide metabolism in taurocholate-induced
      DNA synthesis inhibition.
AB  - BACKGROUND/AIMS: In previous studies we have shown the ability of bile acids to
      reduce the rate of thymidine incorporation into DNA by the regenerating rodent
      liver. The aim of the present work was to investigate the sensitivity of the key
      pathways involved in thymidine metabolism to taurocholate. METHODS/RESULTS:
      Incubation of [14C]-thymidine with mouse liver extracts revealed that addition of
      taurocholate to the reaction medium induced significant dose-dependent inhibition
      in the activity of the salvage nucleotide pathway rate-limiting enzyme, thymidine
      kinase, while other steps of nucleotide metabolism machinery, such as the rate
      limiting enzyme of de novo deoxyribonucleotide synthesis, ribonucleotide
      reductase and the rate-limiting enzyme of thymidine catabolism, dihydropyrimidine
      dehydrogenase were found to be insensitive to inhibition by taurocholate.
      Additional experiments were carried out on isolated perfused rat livers whose
      regeneration was induced by two-thirds hepatectomy and synchronized by
      intravenous administration of reversible ribonucleic reductase inhibitor
      hydroxyurea (bolus: 170 mumol/100 g body weight, plus 10 h infusion: 2.0
      mumol/min per 100 g body weight, from 14 to 24 h after hepatectomy). Hydroxyurea
      treatment was interrupted and liver perfusions were carried out 0, 2, 4 or 8 h
      later. Thymidine incorporation into DNA over 30 min perfusion with media
      containing [14C]-thymidine was measured after separating DNA from acid-soluble
      fraction. A marked increase in DNA synthesis was observed up to 4 h after
      stopping ribonucleotide reductase inhibition. At this time, reduced relevance of
      the salvage pathway can be expected as compared with the de novo released
      pathway. In contrast with the inhibitory effect observed when taurocholate was
      added to the perfusate of untreated regenerating livers, taurocholate was found
      to have no effect on DNA synthesis, at the peak of synchronized DNA synthesis,
      although taurocholate-induced alteration in thymidine metabolism was suggested
      from h.p.l.c. analysis of acid-soluble fraction. CONCLUSIONS: These results
      suggest that effects on the nucleotide metabolism machinery, and hence changes in
      deoxyribonucleotide phosphate pools may underlie the ability of taurocholate to
      affect DNA synthesis by the regenerating rodent liver.

PMID- 8878782
TI  - Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in
      carbon tetrachloride-induced cirrhosis.
AB  - BACKGROUND/AIM: The aim of this study was to investigate the effects of S
      adenosylmethionine on liver peroxidation and liver fibrogenesis in carbon
      tetrachloride-induced cirrhosis. METHODS: Cirrhosis was induced in three groups
      of six rats by repeated injections of carbon tetrachloride over 9 weeks. One
      group of animals was treated only with carbon tetrachloride, and the other two
      received carbon tetrachloride plus S-adenosylmethionine (10 mg/kg intramuscularly
      daily) from week 3 to week 9, and from week 6 to week 9 of the study,
      respectively. Two additional groups of six rats, a control group and a group
      treated only with S-adenosylmethionine, were also studied. Glutathione
      concentration, thiobarbituric acid-reactive substances, collagen content, prolyl
      hydroxylase activity, and procollagen type I mRNA expression were determined in
      liver samples. RESULTS: All carbon tetrachloride-treated rats had cirrhosis at
      the end of the study. Cirrhosis was also present in five of the six carbon
      tetrachloride-treated rats receiving S-adenosylmethionine for 3 weeks, but in
      only one of the six rats that received S-adenosylmethionine for 6 weeks. Hepatic
      glutathione was significantly diminished in carbon tetrachloride-treated rats
      (2.7 +/- 0.3 mumol/g tissue) and returned to normal in rats receiving S
      adenosylmethionine for 3 or 6 weeks (3.7 +/- 0.13 and 3.9 +/- 0.11 mumol/g
      tissue, respectively). The hepatic thiobarbituric acid-reactive substances were
      significantly lower in rats treated with carbon tetrachloride and S
      adenosylmethionine for 6 weeks (98 +/- 5 nmol/g) than in rats treated with carbon
      tetrachloride (134 +/- 12 nmol/g) and in those treated with carbon tetrachloride
      and S-adenosylmethionine for 3 weeks (127 +/- 13 nmol/g). There were no
      differences in either hepatic collagen and prolyl hydroxylase activity between
      rats that received only carbon tetrachloride and those treated with S
      adenosylmethionine for 3 weeks. In contrast, carbon tetrachloride-treated rats
      receiving S-adenosylmethionine for 6 weeks had significantly lower collagen and
      prolyl hydroxylase activity than the other two groups. A much greater increase in
      procollagen type I mRNA was found in carbon tetrachloride-treated rats than in
      rats treated with carbon tetrachloride and S-adenosylmethionine for 6 weeks.
      Furthermore, there was a significant correlation between the hepatic
      thiobarbituric acid-reactive substances and prolyl hydroxylase activity and
      hepatic collagen. CONCLUSIONS: We conclude that the early administration of S
      adenosylmethionine in a model of carbon tetrachloride-induced liver injury
      restores glutathione levels and reduces lipid peroxidation, resulting in less
      advanced liver fibrosis.

PMID- 8878783
TI  - Renal response to methoxamine in portal hypertensive rats: role of prostaglandins
      and nitric oxide.
AB  - BACKGROUND/AIMS: In the present study we have evaluated the role of nitric oxide
      and prostaglandins in the renal vascular response to a vasoconstrictor
      (methoxamine) and to endothelium-dependent (acetylcholine) and independent
      (sodium nitroprusside) vasodilators. METHODS: The experiments were performed in
      isolated and perfused kidneys of portal vein ligated and sham rats under various
      treatments. RESULTS: Baseline renal perfusion pressure was lower in the portal
      vein ligated than in the sham group (37.2 +/- 2.6 vs 48.4 +/- 2.5 mmHg).
      Indomethacin (10(-5)M) did not modify baseline renal perfusion pressure in any
      group, but the nitric oxide inhibitor N(W)-Nitro-L-Arginine (10(-4) M) increased
      it in both sham and portal vein ligated kidneys, but without abolishing the
      differences between them. The vasoconstrictor renal response to methoxamine was
      blunted in portal vein ligated rats compared to controls. Indomethacin did not
      modify this renal hyporesponsiveness, but N(W)-Nitro-L-Arginine completely
      abolished it. In another set of experiments, both acetylcholine and nitroprusside
      caused dose-dependent vasodilation in kidneys, preconstricted with methoxamine,
      from sham and portal vein ligated rats, and there were no significant differences
      between them. N(W)-Nitro-L-Arginine reduced acetylcholine-induced vasodilation
      and did not modify the vasodilation evoked by nitroprusside. CONCLUSIONS: These
      results indicate that the renal vasculature of portal vein ligated rats shows a
      basal reduction in perfusion resistance that is not related to nitric oxide or
      prostaglandins. However, increased nitric oxide production interferes with the
      effects of the alfa-agonist methoxamine. This suggests that nitric oxide plays an
      important role in the modulation of the renal vascular responses to
      vasoconstrictors in portal hypertension.

PMID- 8878785
TI  - Increased hepatocytic mitotic activity as a diagnostic marker of acute arsenic
      intoxication. A report of two cases.
AB  - We report two patients in whom acute arsenic poisoning was associated with a very
      peculiar increase in hepatocytic mitotic activity. The recognition of such an
      unusual picture which is likely to be related to the mitogenic properties of
      arsenic may be of help in the identification of acute arsenic intoxication, a
      life-threatening condition which is difficult to diagnose.

PMID- 8878784
TI  - Elevated serum levels of 90K/MAC-2 BP predict unresponsiveness to alpha
      interferon therapy in chronic HCV hepatitis patients.
AB  - BACKGROUND: The clinical outcome of hepatitis virus infections is though to
      depend on the complex interplay between the host immune response profile and
      virus factors. 90K/MAC-2 BP is a novel member of the Scavenger Receptor Cysteine
      Rich protein superfamily that functions as a molecular alarm signal for the
      cellular immune system against both cancer cells and virus infections. METHODS:
      To assess the significance and the potential clinical usefulness of testing for
      serum levels of 90K/MAC-2 BP in chronic viral hepatitis patients we studied 115
      consecutive patients with chronic HCV hepatitis, 28 HBsAg chronic hepatitis
      patients, 12 asymptomatic HCV carriers and 11 asymptomatic HBV carriers. 103 out
      of the 115 HCV patients have been treated with recombinant alpha 2a-interferon at
      the dose of 3 Mega Units (MU) t.i.w. for 6 months followed by 1.5 MU t.i.w. for 6
      months, and have been followed up for a further 12 months. Serum levels of
      90K/MAC-2 BP were measured by an immunoradiometric assay based on the specific SP
      2 monoclonal antibody. RESULTS AND CONCLUSIONS: Serum 90K/MAC-2 BP levels are
      increased in chronic viral hepatitis patients, being significantly higher in HCV
      than in HBV patients. In chronic HCV hepatitis, serum 90K/MAC-2 BP levels are
      related to both the degree of disease severity and duration of infection.
      Moreover, elevated 90K/MAC-2 BP serum levels are an independent predictor of
      failure to respond to alpha-interferon treatment in a cohort of community
      acquired chronic hepatitis C patients.

PMID- 8878786
TI  - TIPS and refractory ascites. Lessons from the recent history of ascites therapy.

PMID- 8878787
TI  - The transjugular intrahepatic portosystemic shunt.

PMID- 8878788
TI  - Is there a role for immune responses in the pathogenesis of hepatitis C?

PMID- 8878789
TI  - New hepatitis viruses.

PMID- 8878790
TI  - Prospects for xenotransplantation of the liver.
AB  - Because of the tremendous success of clinical transplantation of the liver and
      other organs in the last three decades, the demand for organs for transplantation
      has risen sharply and there is now a substantial shortage. The utilization of
      organs from other species, xenotransplantation, is increasingly viewed as a
      potential solution to this problem. The major limitation to xenotransplantation
      is the formidable immunological barriers that prevent the successful
      transplantation of non-human organs into human recipients. Here we review current
      knowledge about the immunology of xenotransplantation and the limited clinical
      and experimental experience in xenotransplantation of the liver.

PMID- 8878791
TI  - CMV infection of transplant recipients.

PMID- 8878792
TI  - Safe switch to beta-interferon treatment of chronic hepatitis C after alpha
      interferon-induced autoimmune thrombocytopenia.

PMID- 8878793
TI  - Cutaneous necrosis by subcutaneous injection of a-interferon in a patient with
      chronic type B hepatitis.

PMID- 8878794
TI  - Immunomodulation by thalidomide: systematic review of the literature and of
      unpublished observations.
AB  - Three decades of immunological investigations using thalidomide are reviewed.
      Both in vitro and in vivo investigations are in accordance with the clinical
      finding that thalidomide does not impede T-cell competence in the control of
      infection by mycobacteriae. The term immunosuppressant does not apply. The
      immunomodulatory effects of thalidomide are evident in a myriad of
      phenomenological changes, and a molecularly defined common denominator of these
      activities is not known at present. Critical assessment with the objective to
      account for the clinical activity of thalidomide in specific human diseases leads
      to a focus on effects of thalidomide on phagocytic leukocytes and endothelia. The
      former are responsive to thalidomide by modulation of cytokine synthesis in vitro
      and in vivo; this activity can be shown using monocyte-specific stimuli in
      peripheral blood mononuclear cells but also in other phagocytic cells like
      microglia. For technical reasons, endothelial cells have until now been tested
      primarily in vitro. However, there is solid evidence now from intravital
      microscopy that the induction of adhesivity in postcapillary venules by LPS is
      modulated by thalidomide. Altered surface antigen expression has been described
      on leukocytes obtained from humans and experimental animals treated with
      thalidomide, but convincing evidence is lacking for in vitro modulation of
      surface antigen expression on leukocytes (as opposed to the modulation of
      adhesion antigens on endothelial cells stimulated by LPS or exogenous TNF alpha
      in the presence of thalidomide). Therefore, in vivo redistribution is likely to
      account for some, if not all, changes in circulating leukocyte phenotypes. The
      immunopathological conditions most clearly responsive to thalidomide are
      vasculitic alterations of post-capillary venules either in the context of
      mycobacterial infection (in the case of erythema nodosum leprosum) or
      mucocutaneous aphths. In both instances (as in the majority of focal inflammatory
      lesions), leukocyte infiltration and cytokine responses, in particular TNF alpha,
      are present. Thalidomide acts clinically not only by palliation of existing
      lesions but also by prevention of recurrence. The mechanism operates in skin,
      mucosa and parts of the nervous system and is most readily explained by synergism
      of TNF alpha modulation and a separate point of action on leukocyte migration
      patterns.

PMID- 8878795
TI  - Levels of soluble adhesion molecules and cytokines in patients with septic
      multiple organ failure.
AB  - Multiple organ failure (MOF) is a common complication of sepsis or septic shock.
      In this condition, it is believed that activated neutrophils adhere to the
      vascular endothelium and induce various mediators and tissue damage, leading to
      organ damage. We investigated the plasma levels of inflammatory cytokine
      activating neutrophils, soluble adhesive molecules, and endotoxin in 8 patients
      with septic MOF, 15 patients with sepsis but without MOF, and in 5 patients with
      MOF unrelated infection. The soluble intercellular adhesion molecule-1 (sICAM-1)
      concentration in sepsis-complicated groups was significantly higher than that in
      the multiple organ failure (MOF) group without infection. Of sepsis-complicated
      groups, the sICAM-1 value in the MOF group was significantly higher than that in
      the sepsis group without MOF. In sepsis-complicated groups, both soluble
      endothelial-leukocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell
      adhesion molecule-1 (sVCAM-1) concentrations were significantly higher than those
      in the MOF group without infection. However, there was no significant difference
      between the septic MOF group and the sepsis group without MOF. In patients
      showing high levels of soluble adhesion molecule, prognosis was poor, and the
      concentration of soluble adhesion molecules rapidly decreased during recovery
      from MOF. It is speculated that endotoxin and inflammatory cytokines damage
      vascular endothelium as well as various other cells and produce, a large number
      of adhesion molecule, especially in patients with septic MOF, causing leakage of
      adhesion molecules into blood.

PMID- 8878796
TI  - Proinflammatory responses are efficiently induced by homotrimeric but not
      heterotrimeric lymphotoxin ligands.
AB  - The cytokine, lymphotoxin [LT, tumor necrosis factor beta (TNF beta)] is a potent
      mediator of proinflammatory and tumoricidal activities. Soluble lymphotoxin is a
      complex of three LT alpha chains. Its receptors, TNF-R55 and TNF-R75, bind in
      clefts formed by adjacent identical LT alpha monomers. LT also exists as membrane
      anchored heterotrimers comprised of LT alpha and LT beta chains. The major and
      minor membrane forms, LT alpha 1 beta 2 and LT alpha 2 beta 1, respectively, bind
      a unique receptor, LT beta-R. As LT alpha 2 beta 1 expresses an LT alpha-alpha
      cleft, it also binds TNF-R. In this report we have compared the effects of ligand
      engagement of TNF-R and LT beta-R by evaluating the ability of soluble LT alpha
      beta complexes to initiate activities of human umbilical vein endothelial cells
      which are characteristically signalled by TNF. We recently reported that soluble
      LT alpha 1 beta 2 signals via LT beta-R to mediate cytotoxicity of a subset of
      gamma interferon (IFN-gamma) treated carcinomas. We now show that human LT alpha
      beta heterotrimers do not efficiently activate LT beta-R+, TNF-R+ human
      endothelial cells in vitro and only inefficiently mediates lethal toxicity in
      mice. We also show that neither LT alpha beta heterotrimer signals via TNF-R; in
      fact LT alpha 2 beta 1 trimers fail to activate NF-kappa B and rather inhibit
      ligand-induced TNF-R signalling supporting the role for aggregation in TNF-R
      signalling. Thus, the ability of LT alpha beta complexes to efficiently initiate
      tumoricidal but not inflammatory activities distinguishes the LT/LT beta-R from
      the LT/TNF-R pathways and suggest novel strategies for exploiting the LT ligands
      in tumor therapy and for inhibiting TNF-R-mediated inflammatory sequellae.

PMID- 8878797
TI  - New antiepileptic drugs. II. Clinical use.

PMID- 8878798
TI  - Distribution of phospholipase C isozymes in normal human lung tissue and their
      immunohistochemical localization.
AB  - Phospholipase C(PLC) plays a central role in signal transduction and it is
      important in cellular growth, differentiation and transformation. There are
      currently ten known mammalian isozymes of PLC identified and cloned. However,
      there are no report of PLC distribution in human lung tissue or their
      significances in pulmonary diseases. Presence of various PLC isozymes in normal
      human lung tissue was studied from surgical specimens. PLC isozymes in tissue
      extracts of the lung were partially purified by successive chromatographic steps
      on heparin-sepharose CL-6B conventional and TSKgel heparin-5PW HPLC columns and
      their activities were assayed. PLC activity peaks identified in the
      chromatography were immunoblotted with specific antibodies against ten known
      mammalian PLC isozymes(PLC-beta 1-4, -gamma 1-2, and -delta 1-4). In addition,
      immunohistochemical staining of the lung tissue was performed to determine
      subcellular and histological localization of PLC isozymes. The results indicate
      that normal human lungs contain beta 1, beta 3, gamma 1, and delta 1, isozymes of
      PLC. The order of amount present in the lung tissue was PLC-delta 1 > gamma 1 >
      beta 1 >> beta 3, in descending order. On immunohistochemistry, PLC-gamma 1 was
      most widely distributed and was present in bronchiolar epithelium, in type I and
      type II pneumocytes as well as in fibroblasts of the interstitial tissue. PLC
      delta 1 was present in the cytoplasm of the bronchiolar epithelium whereas PLC
      beta 1 was localized to the apical membranous portion of the same epithelium. PLC
      beta 3 was seen in the nucleus of the respiratory and alveolar lining epithelium
      as well as in the nucleus of lung fibroblasts.

PMID- 8878799
TI  - Isocyanate-induced occupational asthma: challenge and immunologic studies.
AB  - Isocyanate is the most prevalent agent in occupational asthma(OA) in Korea. We
      analyzed 43 toluene diisocyanate(TDI) induced OA patients of whom 81% were found
      to be spray painters. The bronchial sensitivity of all subjects was confirmed by
      TDI-bronchial challenge test. Serum-specific IgE antibodies to isocyanate-human
      serum albumin(HSA) conjugate were detected by RAST technique(Pharmacia, Sweden).
      Bronchial challenge test results revealed 21(57%) early, 5 late only, 4 dual, and
      12 atypical responders(5 prolonged immediate, 6 square-shaped, 1 progressive).
      Four(9%) subjects had negative results on the methacholine bronchial challenge
      test. High levels of serum specific IgE antibody to isocyanate-HSA were found in
      17(40%) patients. The prevalence of a specific IgE antibody was not associated
      with a type of TDI-bronchial challenge test response, smoking and atopic status,
      presence of rhino-sinusitis and systemic symptoms, or a degree of airway
      hyperresponsiveness to methacholine(p > 0.05). The period of latency, ranging
      from 3 to 132 months, was significantly longer in high specific IgE responders (p
      < 0.05). These data suggest that 40% of isocyanate-induced occupational asthma
      patients had high specific IgE antibody to isocyanate-HSA conjugate. The presence
      of specific IgE antibody does not seem to correlate with clinical parameters.

PMID- 8878800
TI  - Adjustment of urinary mercury in health risk assessment of mercury.
AB  - The determination of adjustment method of urinary mercury in spot urine is one of
      the important issues in assessing the health risks of mercury workers. But there
      have been debates about whether creatinine or other forms of correction for
      urinary concentration are better in reducing the variation of urinary mercury. We
      evaluated four adjustment methods-specific gravity, creatinine, log creatinine
      and excretion rate-by correlation between values adjusted by the four methods and
      individual exposure levels which were the geometric mean of daily air mercury
      level for 2 or 5 days, and mercury concentrations in 24 hour urine were also
      investigated to compare the results of spot urine. The correlation between values
      of spot urine and mercury exposure level was over 0.8 in all adjustment methods
      for workers who worked over 1 year. All four adjustment methods for urinary
      mercury were found to be similar in assessing the exposure, log creatinine and
      excretion rate method however were not practical to use due to lack of reference
      values, and variable standard values of specific gravity. And the creatinine
      adjusted values were more sensitive in low mercury exposure level. We therefore
      recommend the creatinine adjustment method for adjustment of urinary mercury.

PMID- 8878801
TI  - The clinical significance of cytoplasmic inclusions(CPI) in synovial fluid
      examination.
AB  - The clinical significance of cytoplasmic inclusions(CPI) in synovial fluid(SF)
      examination was evaluated. We examined SF specimens collected from major
      rheumatology clinics in the Philadelphia area during the period of January to
      December 1995. Among 759 patients in the initial study group, 419 cases with
      established diagnoses and full synovial analyses were included. Their diagnoses
      and SF analysis results including leukocyte counts, differential counts and wet
      preparations were collected and analysed. Ninety seven of the 419 SF specimens
      were found to have CPI. CPI were found in SF from almost all rheumatic diseases.
      They were most likely to be found in inflammatory arthropathy including
      rheumatoid arthritis(RA, 46%), juvenile rheumatoid arthritis(JRA, 78%) and
      psoriatic arthritis(55%). On the contrary, CPI were least common in crystal
      induced arthropathy among the inflammatory arthropathy. CPI were found 8 out of
      98 gout cases(8%) and 2 among 53 calcium pyrophosphate dihydrate(CPPD) deposition
      disease(4%). In noninflammatory arthropathy, CPI were found in only 6 cases(6%)
      out of the 103 osteoarthritis(OA). In RA cases with non-inflammatory SF, 4 of the
      20 SF(20%) had CPI while only 6% of OA SF had CPI. OA SF with CPI were all
      noninflammatory SF. In summary, CPI were a common finding on SF examination. CPI
      were more likely to be found in inflammatory arthropathy than noninflammatory.
      Among inflammatory arthropathy, CPI can favor non-crystal arthropathy than
      crystal arthropathy. Awareness of the presence of CPI is suggested as an addendum
      to routine SF analysis. Renewed investigation of the several types of CPI may add
      further to the understanding of joint disease.

PMID- 8878802
TI  - Preputial condition and urinary tract infections.
AB  - Recently, an increase in incidences of urinary tract infections in uncircumcised
      male infants has been reported. However, determining what is the best management
      for the prepuce of newborns and infants is still to be solved. I investigated
      prospectively how much foreskins are retracted with age and what correlations it
      has with urinary tract infection in 122 males children below 15 years of age.
      Under 6 months of age, the majority of the foreskins were unretractable. As they
      got older, over 3 years of age, their prepuces became retractable. The incidence
      of bacteriuria was 11.4% in uncircumcised but none in circumcised and
      hypospadias. In 8 patients showing bacteriuria, their foreskins were retracted
      below 25% in length. Among them, 5 patients, in whom E. coli were grown in their
      urine, showed radiologic renal abnormalities and suffered from high fever
      indicating systemic infection. However, the other 3 cases infected by Proteus
      mirabilis in their urine complained of only local penile symptoms.

PMID- 8878803
TI  - Effects of tretinoin pretreatment on TCA chemical peel in guinea pig skin.
AB  - This study was done to characterize the structural changes in the tretinoin
      pretreatment on trichloroacetic acid(TCA) chemical peel. In guinea pigs, the
      right halves pretreated with tretinoin and the left halves treated nothing were
      compared in their structural changes after TCA chemical peel. Epidermal thickness
      in the tretinoin pretreated group was almost the same in the first and second
      week. But epidermis of the TCA group increased continuously. In the first week,
      mitotic figures in the epidermis were more increased in the TCA group, but those
      in hair follicles were more increased in the tretinoin pretreated group. In the
      second week, mitotic figures in the epidermis were almost same in both group, but
      in hair follicles of the tretinoin pretreated group, mitotic figures were much
      more increased. In alcian blue staining, glycosaminoglycan was stained much more
      strongly in dermis of the TCA group in first week, but was more strongly stained
      in the tretinoin pretreated group in second week. On electron microscopic
      findings, the fibroblasts in upper dermis were larger and had plentier cytoplasm
      with more organelles in the tretinoin pretreated group. Conclusively, tretinoin
      pretreatment on TCA chemical peel sustained the effects of TCA longer and showed
      synergistic effects of TCA and induced enhanced wound healing.

PMID- 8878804
TI  - Exogenous causes of myoglobinuria--review of 26 cases.
AB  - In this article, I review various causes of exogenous myoglobinuria(MU) and its
      pathogenesis in 26 consecutive patients admitted to emergency room, Asan Medical
      Center and determine whether there is a relationship between concentration of
      urine myoglobin(Mb) and acute renal failure(ARF) as a complication of MU. Serum
      and urine Mb were measured by RIA using myoglobin kit(Daiichi, Inc., Tokyo,
      Japan). The most common disorder of MU was septic shock with hypotension,
      followed by crush syndrome, major arterial occlusion by thormbosis, alcohol
      intoxication with status epilepticus, intoxication of unidentified snake venom
      and drug ingestion. On the basis of this limited amount of data, there is a
      significant association between high concentration in urine Mb(> 300 ng/ml) and
      ARF(Fisher's exact test, p < 0.005). To minimize the chances of development of
      ARF, routine urine Mb levels should be checked on patients at risk, especially
      septic shock with hypotension.

PMID- 8878805
TI  - An allograft kidney showing both features of IgA nephropathy and membranous
      glomerulonephritis--a case report.
AB  - We report a case of glomerular disease with both mesangial IgA and subepithelial
      IgG deposits in the allograft kidney. The patient was a 36 year-old man who had
      received a renal allograft 1 year previously. Fifteen days before admission, he
      discovered a microscopic hematuria without clinical evidences of allograft
      rejection. Light microscopy showed diffuse increase of mesangial matrix without
      mesangial cell proliferation. Capillary walls were diffusely and mildly
      thickened. Immunofluorescence microscopy demonstrated both granular deposits of
      IgA in the mesangium and IgG along the capillary walls. On electron microscopy,
      electron-dense deposits were identified not only in the mesangium but also on the
      epithelial side of the glomerular basement membrane.

PMID- 8878806
TI  - Hemangiopericytoma of renal sinus expanding to the renal hilum: an unusual
      presentation causes misinterpretation as transitional cell carcinoma.
AB  - We report a case of renal hemangiopericytoma occurring in renal sinus and
      expanding to the renal hilum. This unusual presentation caused misinterpretation
      of this tumor as transitional cell carcinoma of the renal pelvis clinically. The
      patient who was a 30-year-old woman had a relatively well demarcated solid tumor,
      8 x 6 cm, in the renal sinus of the left kidney.

PMID- 8878807
TI  - Localized periorbital edema as a clinical manifestation of sulfite sensitivity.
AB  - Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique
      clinical presentation of localized periorbital edema on the left eye after
      administration of sulfite-containing dexamethasone. The patient's sulfite
      sensitivity was confirmed by sulfite oral provocation test: periorbital edema on
      the same site developed after ingestion of 200 mg sodium bisulfite. She was non
      atopic and did not complain of any respiratory symptoms. Allergy skin prick test
      with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin
      sensitive urticaria which was confirmed by oral provocation test. In conclusion,
      sulfite can induce a localized periorbital edema, an uncommon manifestation in
      sensitive patients. Further investigations are needed to clarify the pathogenetic
      mechanisms.

PMID- 8878808
TI  - Inclusion body myositis--a case report.
AB  - Inclusion body myositis is a rare myopathy that clinically resembles a chronic
      polymyositis and histopathologically is characterized by the presence of rimmed
      vacuoles containing ultrastructural cytoplasmic degradation products with
      filamentous intranuclear and cytoplasmic inclusions. Since clinical features are
      not uniform, histopathologic and ultrastructural studies are necessary to confirm
      the diagnosis. We report a typical case of inclusion body myositis with
      histopathologic and ultrastructural study. The patient was a 31 year old male who
      presented with progressive weakness of both forearms, hands and lower extremities
      for 10 years.

PMID- 8878809
TI  - Atretic encephalocele/myelocele--case reports with emphasis on pathogenesis.
AB  - Atretic encephaloceles or myelomeningoceles are frequently solid due to
      hamartomatous proliferation of fibrous tissue and blood vessels. Because of the
      fibrous nature of the tumor with no cystic cavity and unusual location with no
      connection to CNS, they are frequently regarded as insignificant hamartomas.
      Apart from this terminology, they are also described as cutaneous meningiomas or
      hamartomas with ectopic meningothelial elements by the presence of meningothelial
      cells. We report a case of atretic encephalocele in the parietal scalp of an 8
      year-old boy and a case of myelomeningocele in the posterior mediastinum of a 31
      year-old woman. The terms atretic encephalocele and myelomeningocele are more
      appropriate for these cases because they include their pathogenesis and the non
      neoplastic nature of the lesion.

PMID- 8878810
TI  - Secretory meningioma--a case report with histopathological, immunohistochemical
      and ultrastructural analysis.
AB  - Secretory meningioma have been described as a distinct variant of meningioma
      based on their histologic, immunohistochemical and ultrastructural features of
      epithelial and secretory differentiation of meningothelial cells with
      accumulation of secretory material in the form of hyaline inclusion. Secretory
      meningioma is also a benign tumor having similar biological behaviour to that of
      typical meningiomas: hence, it is important for it to be recognized and diagnosed
      correctly to avoid unnecessary radiation and chemotherapy. Here we present a case
      of secretory meningioma with typical morphologic features. The patient was a 56
      year-old woman with bilateral visual disturbance. A well-circumscribed mass was
      present in the left frontal lobe of cerebrum with surrounding edema. The tumor
      was composed of whorls of meningothelial cells and abundant intra- and
      extracellular eosinophilic hyaline inclusions which showed immunoreactivity for
      epithelial membrane antigen(EMA) and carcinoembryonic antigen(CEA).
      Ultrastructural features also supported epithelial and secretory differentiation
      of tumor cells.

PMID- 8878811
TI  - The hammerhead ribozyme.

PMID- 8878812
TI  - Molecular palaeontology: understanding catalytic mechanisms in the RNA world by
      excavating clues from a ribozyme three-dimensional structure.

PMID- 8878813
TI  - Hairpin ribozyme: current status and future prospects.

PMID- 8878814
TI  - Facilitators of RNA-RNA annealing: implications for the catalytic cycle of
      hammerhead ribozymes.

PMID- 8878815
TI  - Ribonuclease H-mediated antisense effects in intact human leukaemia cells.

PMID- 8878817
TI  - Second-generation antisense oligonucleotides: structure-activity relationships
      and the design of improved signal-transduction inhibitors.

PMID- 8878816
TI  - Antisense oligonucleotides as inhibitors of signal transduction: development from
      research tools to therapeutic agents.

PMID- 8878818
TI  - Regulation of the synaptic vesicle cycle in Drosophila.

PMID- 8878820
TI  - SNAPs and SNAREs in exocytosis in chromaffin cells.

PMID- 8878819
TI  - Role of protein kinases in nerve terminal maturation and function.

PMID- 8878821
TI  - Role of Rab3a in neurotransmitter and hormone release: a discussion of recent
      data.

PMID- 8878822
TI  - Mammalian Unc-13 homologues as possible regulators of neurotransmitter release.

PMID- 8878823
TI  - Protein-protein interactions in synaptic vesicle exocytosis.

PMID- 8878824
TI  - SNAP-25, enSNAREd in neurotransmission and regulation of behaviour.

PMID- 8878825
TI  - Organization of isoprenoid biosynthesis.

PMID- 8878826
TI  - Chemical biology of isoprenylation/methylation.

PMID- 8878827
TI  - Farnesyltransferase inhibitors: a new class of cancer chemotherapeutics.

PMID- 8878828
TI  - Rational design of Ras prenyltransferase inhibitors as potential anticancer
      drugs.

PMID- 8878829
TI  - Geranylgeranylation of Rab proteins.

PMID- 8878830
TI  - Prenylation-dependent interaction of Rab proteins with GDP dissociation
      inhibitors.

PMID- 8878831
TI  - C-terminal motifs found in Ras-superfamily G-proteins: CAAX and C-seven motifs.

PMID- 8878832
TI  - Lipid modifications of G-protein-coupled receptor kinases.

PMID- 8878833
TI  - M-factor, a farnesylated mating factor from the fission yeast Schizosaccharomyces
      pombe.

PMID- 8878835
TI  - Structure-function relationships in the dual-function photosynthetic-respiratory
      electron-transport assembly of cyanobacteria (blue-green algae).

PMID- 8878834
TI  - Retinoylation of proteins in mammalian cells.

PMID- 8878836
TI  - Biogenesis of the electron-transfer complexes in Chlamydomonas reinhardtii.

PMID- 8878837
TI  - Detection and characterization of a complex I-like NADH-specific dehydrogenase
      from pea thylakoids.

PMID- 8878838
TI  - Role of NAD(+)-dependent 'malic' enzyme and pyruvate dehydrogenase complex in
      leaf metabolism.

PMID- 8878839
TI  - Developmental regulation of respiratory activity and protein import in plant
      mitochondria.

PMID- 8878840
TI  - Protein targeting and translocation in cyanobacterial membrane biogenesis.

PMID- 8878841
TI  - A specific porin is involved in the malate shuttle of leaf peroxisomes.

PMID- 8878842
TI  - Use of barley mutants to study the control of photorespiratory metabolism.

PMID- 8878843
TI  - Function of the chloroplastic malate valve for respiration during photosynthesis.

PMID- 8878844
TI  - A role for glucose-6-phosphate dehydrogenase in short- and long-term regulation
      of photosynthetic and respiratory carbon and nitrogen metabolism in nitrogen
      limited Chlamydomonas reinhardtii.

PMID- 8878845
TI  - Overview of bioactive compounds in foods.

PMID- 8878846
TI  - Bioavailability of dietary minerals.

PMID- 8878847
TI  - The metabolism of dietary nitrites and nitrates.

PMID- 8878848
TI  - Role of dietary flavonoids in protection against cancer and coronary heart
      disease.

PMID- 8878849
TI  - Antioxidant activities of flavonoids as bioactive components of food.

PMID- 8878850
TI  - Role of dietary phyto-oestrogens in the protection against cancer and heart
      disease.

PMID- 8878851
TI  - Intake levels, sites of action and excretion routes of the cholesterol-elevating
      diterpenes from coffee beans in humans.

PMID- 8878852
TI  - Chemoprotection against cancer by isothiocyanates and glucosinolates.

PMID- 8878853
TI  - Allium vegetables: their role in the prevention of cancer.

PMID- 8878855
TI  - Substrates for fermentation in the large bowel.

PMID- 8878854
TI  - Bioactive lipids in foods.

PMID- 8878856
TI  - Opportunities for the genetic manipulation of antioxidants in plant foods.

PMID- 8878857
TI  - Mammalian amino acid transporters and their regulation: introduction.

PMID- 8878859
TI  - Structure/function relationships in glutamate transporters.

PMID- 8878858
TI  - Rat placental amino acid transport after protein-deprivation-induced intrauterine
      growth retardation.

PMID- 8878860
TI  - Regulation of cationic amino acid transporter (CAT) gene expression.
AB  - The Cat family of genes have revealed unexpected complexity and regulation. The
      first 5 years of research have been productive, yet many important questions
      remain to be addressed. A major problem for the field of amino acid transport is
      a severe paucity of data on the structure of these proteins and their arrangement
      in membranes. There is a need for epitope-specific antisera to distinguish the
      mCAT2/2A proteins and reagents that will specifically block transport to each of
      these proteins. The question of gene redundancy will be answered by using genetic
      approaches such as targeted gene ablation, tissue-specific gene knockout and
      transgenic overexpression. From this information and more physiological analysis,
      it will be possible to determine the role and significance of these transport
      proteins.

PMID- 8878861
TI  - Transcriptional regulation of the betaine/gamma-aminobutyric acid transporter by
      hypertonicity.

PMID- 8878862
TI  - Role of the b(o,+)-like amino acid-transport system in the renal reabsorption of
      cystine and dibasic amino acids.

PMID- 8878863
TI  - Modulation of transport systems for neutral and anionic amino acids in
      mesenchymal cells.

PMID- 8878864
TI  - Amino acid transport in heart and skeletal muscle and the functional
      consequences.

PMID- 8878865
TI  - Nitric oxide synthases.

PMID- 8878866
TI  - Evolution of glutathione transferases and related enzymes for the protection of
      cells against electrophiles.

PMID- 8878867
TI  - Glutathione in disease.

PMID- 8878868
TI  - The intracellular reducing environment modulates cytoregulation and cytotoxicity
      by reactive oxygen species.

PMID- 8878870
TI  - A strategy for identifying gel-separated proteins in sequence databases by MS
      alone.

PMID- 8878871
TI  - Matrix-assisted laser desorption ionization MS: a progress report.

PMID- 8878869
TI  - Aldose reductase: monosaccharide autoxidation and NADPH binding.

PMID- 8878872
TI  - DNA sequence analysis by matrix-assisted laser desorption ionization MS.
AB  - The major advantage of this procedure is that, as detailed in Figure 5, the
      entire sequence of an oligonucleotide is determined in less than 1 h using
      inexpensive reagents. DE MS, because of its significantly higher resolving power,
      permits analysis of oligonucleotides as long as 50 bases, about twice as long as
      that which is possible without DE. Phosphorothioates can be sequenced after
      oxidation to the phosphodiester state. We have also found that the enzymes will
      digest through a number of modifying and protecting groups on DNA and RNA,
      including 2'-amino- and 2'-alkyl-substituted hydroxy groups. The resultant
      spectra can confirm not only the presence, but also the position, of modifying
      groups on both DNA and RNA molecules.

PMID- 8878873
TI  - Identification of oligosaccharides by matrix-assisted laser desorption ionization
      and electrospray MS.

PMID- 8878874
TI  - Analysis of hydrophobic proteins and peptides by electrospray ionization MS.

PMID- 8878875
TI  - The use of electrospray ionization MS to determine the structure of glycans in
      intact glycoproteins.

PMID- 8878876
TI  - Use of continuous-flow combustion MS in studies of human metabolism.

PMID- 8878877
TI  - The use of automated electrospray ionization tandem MS for the diagnosis of
      inborn errors of metabolism from dried blood spots.

PMID- 8878878
TI  - Qualitative and quantitative MS analysis of cyclic nucleotides and related
      enzymes.

PMID- 8878879
TI  - Applications of sustained off-resonance irradiation (SORI) and quadrupolar
      excitation axialization (QEA) for the characterization of biomolecules by Fourier
      transform mass spectrometry (FTMS).

PMID- 8878881
TI  - Neutral endopeptidase activity in breast cysts.

PMID- 8878880
TI  - Use of HPLC with inductively coupled plasma mass spectrometry (ICP-MS) for trace
      element speciation studies in biological materials.

PMID- 8878883
TI  - The glycosylation of human recombinant alpha-1-antitrypsin expressed in
      transgenic mice.

PMID- 8878882
TI  - Protein kinase C does not acutely modulate protein kinase A activity in mammary
      gland acini prepared from mid-pregnant and mid-lactating rats.

PMID- 8878884
TI  - S100A3 mRNA expression displays an inverse correlation to breast cancer
      progression.

PMID- 8878885
TI  - Protein interactions between S100A4 (p9Ka) and other cellular proteins identified
      using in vitro methods.

PMID- 8878886
TI  - A growth factor activity in bovine milk.

PMID- 8878887
TI  - Oestrogen and insulin interact at the level of transcription in breast cancer
      cells.

PMID- 8878888
TI  - Synergism between oestradiol and cAMP for specific gene transcription in breast
      cancer cells.

PMID- 8878889
TI  - Extracellular matrix controls the prolactin signalling pathway in mammary
      epithelial cells.

PMID- 8878890
TI  - The differential expression of desmocollin isoforms in mammary epithelia.

PMID- 8878891
TI  - Programmed cell death and the mammary gland--the involvement of the Bcl-2 family
      members in the control of epithelial apoptosis.

PMID- 8878892
TI  - The role of the extracellular matrix and lactogenic hormones in mammary gland
      apoptosis.

PMID- 8878893
TI  - Requirement for beta 1 integrins in the development of mouse mammary gland.

PMID- 8878894
TI  - The choline content of human breast milk expressed during the first few weeks of
      lactation.

PMID- 8878896
TI  - Regulatory elements in the first intron of the rat S100A4 (p9Ka) gene.

PMID- 8878895
TI  - Hormonal control of transcription from two mammary specific promoters in a rat
      mammary epithelial cell line.

PMID- 8878897
TI  - The identification of metastasis-related gene products in a rodent mammary tumour
      model.

PMID- 8878898
TI  - Identification of the region(s) of human DNA responsible for metastasis in breast
      cancer.

PMID- 8878899
TI  - Heparan sulphate in breast cancer cells.

PMID- 8878900
TI  - Growth & mammary abnormalities in mice containing an altered calcium-binding
      protein transgene.

PMID- 8878901
TI  - Identification of cell types in the developing goat mammary gland.

PMID- 8878902
TI  - Potentiation of the growth-stimulatory effects of aFGF by heparin in Rama 27
      fibroblasts.

PMID- 8878904
TI  - Induction of a variant acetyl-CoA carboxylase mRNA in ovine mammary gland during
      lactation.

PMID- 8878903
TI  - Prolactin modulates G-protein levels in the rat mammary gland.

PMID- 8878905
TI  - 3,4,3',4'-tetrachlorobiphenyl acts as an oestrogen and can promote breast tumour
      growth.

PMID- 8878906
TI  - Overexpression of insulin-like growth factor II alters serum sensitivity of
      breast cancer cells.

PMID- 8878907
TI  - Association between insulin-like growth factor receptors & cell density in breast
      cancer cells.

PMID- 8878908
TI  - Overexpression of insulin-like growth factor II in human breast cancer cells.

PMID- 8878909
TI  - Retinoic acid inhibits growth of breast cancer cells in the short-term but not
      the long-term.

PMID- 8878910
TI  - Mechanism of action of interferon on oestrogen receptor function.

PMID- 8878911
TI  - Isolation, characterisation and hormone-dependent expression of the porcine whey
      acidic protein.

PMID- 8878912
TI  - Biphasic effect of thrombospondin-1 (TSP-1) in the regulation of angiogenesis in
      human breast carcinoma.

PMID- 8878913
TI  - Primary culture of ovine mammary epithelial cells.

PMID- 8878914
TI  - Differential regulation of members of the family of signal transducers and
      activators of transcription during mammary gland development.

PMID- 8878915
TI  - Derivation of conditionally immortal mammary epithelial cell lines.

PMID- 8878916
TI  - Identification of transcripts showing differential expression in the developing
      mammary gland using differential display.

PMID- 8878917
TI  - Epidermal growth factor-regulated signal transduction in hormone dependent and
      independent breast cancer.

PMID- 8878918
TI  - Evidence that intracellular phosphatidate may regulate breast cancer cell
      invasion and metastasis.

PMID- 8878919
TI  - Identification of pro-oxidant or antioxidant characteristics of proteins and
      enzymes in membranes; use of liposome-entrapped proteins and other thiol
      containing compounds.

PMID- 8878920
TI  - Is there an optimal membrane protein content determined by membrane stability to
      lipid peroxidation? Disease and ageing consideration.

PMID- 8878921
TI  - Investigation of the role of protein kinase C inhibition in the calcium
      independent relaxant effects of oestrogens on isolated rat aorta.

PMID- 8878922
TI  - Production of extracellular lignocellulose degrading enzymes by Thermomonospora
      fusca BD25.

PMID- 8878923
TI  - Release of the bioactive compound, ferulic acid, from malt extracts.

PMID- 8878925
TI  - Allyl isothiocyanate selectively kills undifferentiated HT29 cells in vitro and
      suppresses aberrant crypt foci in the colonic mucosa of rats.

PMID- 8878924
TI  - Effect of ethoxyquin on glutathione levels and peroxidisability of rat liver
      membranes.

PMID- 8878926
TI  - Raw starch digestion.

PMID- 8878927
TI  - Glucosinolates as bioactive components of Brassica vegetables: induction of
      cytochrome P450 1A1 in Hep G2 cells as assessed using transient transfection.

PMID- 8878928
TI  - Solubilisation of ferulic acid from plant cell wall materials in a model human
      gut system.

PMID- 8878930
TI  - A major bioactive component of plant cell walls, ferulic acid, influences
      feruloyl esterase production in Aspergillus niger.

PMID- 8878929
TI  - Can carotenoids reduce oxidation-induced cataract?

PMID- 8878931
TI  - Dietary beta-carotene supplementation modulates the production of tumour necrosis
      factor-alpha by human monocytes.

PMID- 8878932
TI  - Beta-carotene supplementation enhances the expression of functionally associated
      molecules on human monocytes.

PMID- 8878933
TI  - Influence of n-3 polyunsaturated fatty acids (PUFA) on the antigen-presenting
      function of human monocytes.

PMID- 8878934
TI  - Antioxidant properties of ethanolic and aqueous extracts of green tea compared to
      black tea.

PMID- 8878935
TI  - Potent antioxidant properties of novel apple-derived flavonoids with commercial
      potential as food additives.

PMID- 8878936
TI  - Inhibition of liposomal lipid peroxidation by isoflavonoid type phyto-oestrogens
      from soybeans of different countries of origin.

PMID- 8878937
TI  - Effect of processing on saponin content and composition of chickpeas.

PMID- 8878938
TI  - Development of an immunoassay to measure the absorption of dietary
      furanocoumarins in humans.

PMID- 8878939
TI  - Interaction of immobilised food dye residues with gut proteins.

PMID- 8878940
TI  - Contribution of alpha-tocopherol in HDL3 to inhibition of LDL oxidation by human
      macrophages.

PMID- 8878941
TI  - Effect of flavones on glucose-induced changes in human serum albumen.

PMID- 8878942
TI  - Characterization and electron transfer kinetics of wild type and a mutant bf
      complex in Chlamydomonas reinhardtii.

PMID- 8878943
TI  - Effect of trampling on photosynthesis and respiration in Plantago lanceolata.

PMID- 8878944
TI  - Does the cytochrome bd terminal oxidase complex have a "pulsed" form?

PMID- 8878945
TI  - Nitrogenase-specific proteolytic activity in the unicellular cyanobacterium
      Gloeothece.

PMID- 8878946
TI  - Regulation of photosynthetic enzymes in light- or dark-grown cyanobacterium
      Nostoc sp. Mac.

PMID- 8878947
TI  - Problem-based biochemistry practicals for students of environmental and marine
      biology.

PMID- 8878948
TI  - Characterisation of alginates from mucoid strains of Pseudomonas aeruginosa.

PMID- 8878949
TI  - Overexpression of the GDP-mannose dehydrogenase gene from Pseudomonas aeruginosa.

PMID- 8878950
TI  - Colonisation of cystic fibrosis patients by non-mucoid Pseudomonas aeruginosa-
      characterisation of the alginate from mucoid variants.

PMID- 8878951
TI  - Expression of the Klebsiella pneumoniae alginate lyase gene in Pseudomonas
      aeruginosa--effect on alginate structure.

PMID- 8878952
TI  - Uptake and effects of antisense oligodeoxynucleotides specific for rat
      metallothionein -1 and -2 mRNA in H4 rat hepatoma cells in culture.

PMID- 8878953
TI  - Specificity of ribozymes against the bcr-abl mRNAs in vitro.

PMID- 8878954
TI  - Antisense oligonucleotide-mediated inhibition of mutant p53 expression.

PMID- 8878955
TI  - Real-time imaging of transcription in living cells and tissues.

PMID- 8878956
TI  - Molecular interactions in the RNA bacteriophage MS2.

PMID- 8878957
TI  - Development of a novel drug-delivery system using bacteriophage MS2 capsids.

PMID- 8878958
TI  - Sequence analysis of the capsid gene of feline calicivirus strain F65.

PMID- 8878959
TI  - Characterisation of transcription factors in African swine fever virus.

PMID- 8878960
TI  - Evolutionary relationships between gibbon subgenera inferred from DNA sequence
      data.

PMID- 8878961
TI  - The cyanobacterium Anabaena flos-aquae possesses diadenosine 5',5'''-P1,P4
      tetraphosphate (Ap4A) phosphorylase activity.

PMID- 8878962
TI  - Molecular cloning of diadenosine 5',5'''-P1,P4-tetraphosphate
      pyrophosphohydrolase (Ap4A hydrolase) from porcine small intestine: relationship
      to other enzymes of Ap4A catabolism.

PMID- 8878963
TI  - GTP:GTP guanylyltransferase activity from encysted embryos of the brine shrimp
      Artemia is associated with a single 110 kDa polypeptide.

PMID- 8878964
TI  - Action of DNA gyrase at RIP elements in E. coli.

PMID- 8878965
TI  - The structure and mechanism of DNA gyrase from divergent bacterial species.

PMID- 8878966
TI  - Identification and interpretation of latent periodicity within DNA sequences.

PMID- 8878967
TI  - Gene transfer into cultured bovine ciliary epithelial cells using adenovirus
      vectors.

PMID- 8878968
TI  - Analysis of the 5'-flanking region of the rat phenylalanine hydroxylase gene.

PMID- 8878969
TI  - Differences in the amount of glutamate released by neonatal and adult
      synaptosomes under conditions of in vitro ischaemia/reperfusion.

PMID- 8878970
TI  - The effect of down-regulation and long-term inhibition of protein kinase C on
      noradrenaline secretion in the neuroblastoma cell line SH-SY5Y.

PMID- 8878971
TI  - Translocation of the PKC isoforms present in the human neuroblastoma, SH-SY5Y,
      following short-term treatment with the phorbol ester, TPA.

PMID- 8878972
TI  - The occurrence of noradrenaline and neuropeptide Y in large dense-cored vesicles
      in the human neuroblastoma SH-SY5Y.

PMID- 8878973
TI  - The target of PKC induced suppression of adenosine inhibition of glutamate
      release from synaptosomes is downstream of the A1 receptor and G-protein
      coupling.

PMID- 8878974
TI  - Transmitter exocytosis in cultured cerebellar granule cells stimulated with an
      applied electrical field.

PMID- 8878975
TI  - A role for presynaptic AMPA receptors in the enhancement of neuronal glutamate
      release by kainic acid.

PMID- 8878976
TI  - Isolation of ptb1, a gene for the beta-subunit of a prenyltransferase from
      fission yeast.

PMID- 8878977
TI  - Protein isoprenylation in Trypanosoma brucei brucei.

PMID- 8878978
TI  - Carbon sources for fatty acid and sterol biosynthesis in Leishmania species.

PMID- 8878979
TI  - Activation of 12- and 15-lipoxygenase in the cardiopulmonary system by
      hemorrhagic events.

PMID- 8878980
TI  - Purification of the enzymes of ecdysteroid 3-epimerization from the midgut of the
      cotton leafworm, Spodoptera littoralis.

PMID- 8878981
TI  - Evidence for the existence of juvenile hormones in ticks.

PMID- 8878982
TI  - Ecdysteroid inactivation in response to elevated levels of 20-hydroxyecdysone or
      an agonist, RH 5849 in the tobacco hornworm, Manduca sexta.

PMID- 8878983
TI  - Trypanolytic activity in vivo of plasma from patients with schistosomiasis
      against the African trypanosome, Trypanosoma brucei brucei.

PMID- 8878984
TI  - Cyclic AMP analogues stimulate triacylglycerol synthesis but not cholesterol
      esterification in J774 macrophages.

PMID- 8878985
TI  - The entrapment of mannose-terminated glucocerebrosidase (Alglucerase) in human
      carrier erythrocytes.

PMID- 8878986
TI  - The entrapment of polyethylene glycol-bound adenosine deaminase (Pegademase) in
      human carrier erythrocytes.

PMID- 8878988
TI  - A role for calcium and annexins in the formation of caveolae.

PMID- 8878987
TI  - Elucidating the role of gonadotrophins in endometrial cancer cell growth.

PMID- 8878989
TI  - Effect of repeated exposure to ultraviolet A (UVA) radiation on the activities of
      fibroblasts in three dimensional culture.

PMID- 8878990
TI  - Thrombospondin-1 induces DNA synthesis and migration in human vascular smooth
      muscle cells.

PMID- 8878991
TI  - Rubredoxin/rubredoxin reductase of Pseudomonas oleovorans: a model system for
      investigating interprotein electron transfer.

PMID- 8878992
TI  - Near infrared spectroscopy of nitrosyl haemoglobin--relevance to in vivo
      detection of nitric oxide.

PMID- 8878993
TI  - Modulation of the glutathione redox state in adult astrocytes.

PMID- 8878994
TI  - Possible interaction of nitric oxide with the ferryl intermediate of cytochrome c
      oxidase.

PMID- 8878995
TI  - Free fatty acids as modulators of cytochrome c oxidase activity.

PMID- 8878997
TI  - Glucuronate metabolism in the mammalian eye lens--origin of xylitol.

PMID- 8878996
TI  - Measurement of glutathione as a marker of oxidative stress in CNS reaggregate
      cultures.

PMID- 8878998
TI  - Native immunoaffinity-isolated apolipoprotein E-containing high-density
      lipoprotein particles inhibit platelet aggregation.

PMID- 8878999
TI  - Redox reaction of the novel non-haem glycosylated peroxidases from thermophilic
      actinomycete Thermomonospora fusca BD25.

PMID- 8879000
TI  - Electron transfer in trimethylamine dehydrogenase: directed mutagenesis of a
      potential tunneling pathway.

PMID- 8879001
TI  - Inhibition of mitochondrial beta-oxidation in the heart by increased redox state
      of the ubiquinone pool.

PMID- 8879002
TI  - Products of aldose reductase catalysed reduction of aldosuloses ("osones").

PMID- 8879003
TI  - Effect of dithiothreitol on quality control of GPI-anchor addition.

PMID- 8879004
TI  - Investigations into the action of a novel nitric oxide donor on cellular
      respiration.

PMID- 8879005
TI  - Influence of phenolics on protein binding to the antioxidant responsive element
      (ARE).

PMID- 8879006
TI  - The peroxidase activity of glutathione S-transferase A1-1 on hydroperoxy
      phospholipids.

PMID- 8879007
TI  - Evidence for murine macrophage nitric oxide synthesis in the absence of exogenous
      L-arginine.

PMID- 8879008
TI  - The variation of Km for oxygen of cytochrome oxidase with turnover under de
      energized and energized conditions.

PMID- 8879009
TI  - A new EPR signal from cytochrome oxidase--evidence for conformational flexibility
      at the CuB site?

PMID- 8879010
TI  - Why methanopterin? Comparative bioenergetics of the reactions catalyzed by
      methylene tetrahydrofolate reductase and methylene tetrahydromethanopterin
      reductase.

PMID- 8879011
TI  - Induction of thiol recycling by protein kinase C: a potentially pro-oxidant
      pathway for low-density lipoprotein oxidation.

PMID- 8879012
TI  - Studies on the enhancement of the reactivity of the (Cys-25)-S-/(His159)-Im+H ion
      pair of papain by deprotonation across pKa 4.

PMID- 8879013
TI  - Fluorescent labelling of pyruvate carboxylase with 4-acetamido-4'-(iodacetyl)
      aminostilbene-2,2'-disulfonic acid (AIDA) provides a means of monitoring
      substrate binding.

PMID- 8879014
TI  - Cloning and functional expression of pig kidney aminopeptidase P.

PMID- 8879015
TI  - Mutagenesis and modeling of endothelin converting enzyme.

PMID- 8879016
TI  - 2-oxoaldehydes, glyoxalase I and oxidative stress.

PMID- 8879017
TI  - Investigation of electrostatic interactions and binding effects in papin-ligand
      interaction.

PMID- 8879018
TI  - Assay of adenylyl cyclase activity by quantitative mass spectrometry.

PMID- 8879019
TI  - Analysis by gas chromatography-mass spectrometry of the fatty acid composition
      during temperature adaptation in Aphanizomenon flos-aquae, a diazotrophic
      cyanobacterium from the Baltic Sea.

PMID- 8879020
TI  - Trace analysis of arthropod hormones by liquid chromatography-atmospheric
      pressure chemical ionization/mass spectrometry.

PMID- 8879021
TI  - Modification of the iron protein of Gloeothece nitrogenase: a mass spectrometric
      study.

PMID- 8879022
TI  - Characterisation and purification of recombinant GLUT1 expressed in insect cells.

PMID- 8879023
TI  - Induction of the stress protein Grp75 by amino acid deprivation in CHO cells does
      not involve an increase in Grp75 mRNA levels.

PMID- 8879024
TI  - Metabolism of arginine to citrulline by rat gastric mucosal cells.

PMID- 8879025
TI  - Induction of high affinity glutamate transport activity by amino acid deprivation
      is dependent on cellular glutamate concentrations in renal epithelial cells does
      not involve an increase in the amount of transporter protein.

PMID- 8879026
TI  - The use of Langendorff perfused guinea-pig heart to study the efflux of amino
      acids from heart cells.

PMID- 8879027
TI  - Metabolic control analysis of purine biosynthesis from serine in Molt-4 cells.

PMID- 8879028
TI  - Differing effects of polyamines on nitric oxide synthase.

PMID- 8879029
TI  - Heat shock protein 70 expression in skeletal muscle.

PMID- 8879031
TI  - Changes in the intracellular concentration of myocardial glutamine in patients
      undergoing coronary artery bypass surgery using crystalloid and blood
      cardioplegia.

PMID- 8879030
TI  - Expression of programmed cell death-related genes in dystrophic mdx and control
      mouse muscle.

PMID- 8879032
TI  - Catabolism of arginine and ornithine in perfused rat liver; localisation and
      regulation.

PMID- 8879033
TI  - Expression of Fc gamma RIII in neutrophils in rheumatoid arthritis.

PMID- 8879034
TI  - Preservation of the activity of NADPH oxidase in human monocyte/macrophages.

PMID- 8879035
TI  - Regulation of neutrophil apoptosis by diadenosine pentaphosphate and GM-CSF.

PMID- 8879036
TI  - Modulation of neutrophil apoptosis by pharmacological agents.

PMID- 8879037
TI  - Gene expression by inflammatory neutrophils: stimulation of interleukin-1 beta
      production by rheumatoid synovial fluid.

PMID- 8879038
TI  - Do stress proteins have a regulatory role in autoimmune rheumatoid arthritis?

PMID- 8879039
TI  - Maternal immunization modulates the primary response repertoire in newborn mice.

PMID- 8879040
TI  - Hybrid antibodies monitoring receptor profiles on lymphocyte subsets.

PMID- 8879041
TI  - Procorticotrophin releasing hormone is endoproteolytically processed by the
      prohormone convertase PC2 but not by PC1 within stably transfected CHO-K1 cells.

PMID- 8879042
TI  - Lectin binding of pregnancy-associated plasma protein A purified from different
      sources.

PMID- 8879044
TI  - Aluminium-induced changes in amyloid precursor protein mRNA expression.

PMID- 8879045
TI  - Basic fibroblast growth factor and colorectal carcinoma invasion.

PMID- 8879043
TI  - Aluminium activation of "immediate early" gene expression in Swiss 3T3
      fibroblasts.

PMID- 8879046
TI  - Defining the role of Sxa1 during pheromone adaptation in Schizosaccharomyces
      pombe.

PMID- 8879047
TI  - Maturation of Krp1, an endopeptidase from the fission yeast Schizosaccharomyces
      pombe.

PMID- 8879048
TI  - Purification of Sxa2, a carboxypeptidase involved in pheromone recovery in
      fission yeast.

PMID- 8879049
TI  - Biochemical determinants of food iron availability: soyabean iron
      characteristics.

PMID- 8879050
TI  - Biochemical determinants of food iron availability: soya fibre and iron
      interactions.

PMID- 8879051
TI  - Intracranial hypotension.
AB  - Intracranial hypotension (IH) is present when cerebrospinal fluid (CSF) pressure
      is 60mm H2O or lower and there has been no previous dural puncture. IH is more
      common in women than in men (3:1). Orthostatic headache is the cardinal symptom.
      Visual, auditory, and other symptoms occur. Postulated mechanisms include sagging
      of the brain, dilation of intracranial veins, and activation of adenosine
      receptors. Examination may disclose visual field defects. The condition may be
      primary (probably related to an occult dural leak) or secondary to many causes
      that include lumbar puncture, trauma, pneumonectomy, diabetic coma, and uremia.
      Patients with postural headache should undergo neuroimaging prior to lumbar
      puncture. Radionuclide cisternography is the most sensitive means of
      demonstrating a CSF fistula. Severe, intractable headache associated with IH may
      respond to intravenous of oral caffeine. An epidural blood patch and epidural
      infusion of normal saline are treatment measures for symptoms of IH that follow
      lumbar puncture.

PMID- 8879052
TI  - Clinical spectrum of mitochondrial diseases.
AB  - Mitochondrial diseases include myopathies and multisystem disorders. They are
      characterized by morphologic and biochemical abnormalities of mitochondria. Their
      genetic characteristics-maternal inheritance, heteroplasmy, mitotic segregation,
      and threshold effect-are unique. The clinical phenotypes are considerably
      heterogeneous, but the clinical presentation in many cases is characteristic or
      suggestive. We review the clinical features of the most prevalent mitochondrial
      encephalomyopathy syndromes, their molecular genetic basis, isolated clinical
      symptoms, and uncommon presentations. Molecular genetic diagnosis is available
      for the common syndromes and has revolutionized their diagnosis. Future
      therapeutic advances, based on the precise genetic etiology, are anticipated.
      Mitochondrial dysfunction may be a more frequent pathogenetic mechanism than the
      prevalence of the classic mitochondrial syndromes would indicate, as there is an
      association between the accumulation of mitochondrial DNA mutations in
      postmitotic tissues and neurologic and systemic degenerative diseases.

PMID- 8879053
TI  - Opsoclonus.
AB  - Opsoclonus is a rare disorder of the saccadic system, in which fixation is
      continuously interrupted by multivectorial, back-to-back saccades that at times
      can be seen only with an ophthalmoscope. To diagnose it reliably, eye movement
      recording is required. Opsoclonus may be a harbinger of an occult malignancy,
      though many cases are postinfectious, toxic-metabolic or idiopathic. The
      underlying malignancy is usually neural crest tumors in children and lung,
      breast, or gynecologic cancer in adults. Opsoclonus can be accompanied by
      myoclonus and ataxia. Concurrent appearance of oscillations affecting eyes and
      limbs suggests a common brainstem generator. Dysfunction of the glycinergic
      omnipause neurons in the nucleus raphe interpositus has been proposed.
      Autoantibodies against neural epitopes shared with a tumor are implicated in the
      pathogenesis of opsoclonus in paraneoplastic cases. Because of the association
      with malignancies, full oncological work-up is indicated in every case.
      Coexisting opsoclonus carries a relatively good prognosis for the cancer;
      however, the neurologic disability may remain even if the tumor has been
      arrested. New, potentially effective immunoadsorption therapy for opsoclonus is
      currently under investigation.

PMID- 8879054
TI  - Dural arteriovenous fistula of the spinal cord: an uncommon cause of myelopathy.
AB  - Dural arteriovenous fistula is an uncommon cause of myelopathy. The nidus of the
      malformation is on or within the dura and results in a mass of serpentine vessels
      on the dorsal surface of the spinal cord, usually at low thoracic or lumbar
      levels. Onset is usually between ages 40 and 70 years. Male to female ratio is
      4:1. Symptoms include pain, progressive proximal weakness of lower limbs, saddle
      area numbness, claudication, and difficulty with urination. Course may be
      fluctuating or slowly progressive. Signs include upper and lower motor neuron
      abnormalities and nondermatomal sensory loss. Spinal bruit is rare. Magnetic
      resonance imaging may show an enlarged cord or abnormalities on its dorsal
      surface. Myelography (patient prone and supine) is the procedure of choice. Motor
      neuron disease, disc disease, spinal cord tumor, and multiple sclerosis are
      differential considerations. Untreated patients have a poor prognosis. Excision
      of the nidus, ligation of the draining vein, and endovascular embolization may be
      helpful even in patients with severe deficits.

PMID- 8879055
TI  - Nonconvulsive status epilepticus.

PMID- 8879056
TI  - Dementia: not always a disease of the elderly.

PMID- 8879057
TI  - Congenital neuromuscular diseases presenting in adulthood.

PMID- 8879058
TI  - Vertigo: some uncommon causes of a common problem.
AB  - Vertigo, an extremely common symptom, may be caused by numerous disorders
      affecting the central or peripheral vestibular systems. Patients can usually be
      categorized into four groups based on the clinical presentation: monophasic,
      prolonged episodes of vertigo due to acute unilateral vestibular hypofunction;
      recurrent episodes of vertigo, due to transient vestibular dysfunction; vertigo
      provoked by changes in head position with respect to gravity (positional
      vertigo); and bilateral vestibulopathies, which present with imbalance and
      oscillopsia. Although each clinical syndrome is usually caused by a limited
      number of disorders, many less common entities must be considered in the
      differential diagnosis. This article reviews the clinical presentation of the
      less common causes of vestibular syndromes and discusses their medical and
      nonmedical management.

PMID- 8879059
TI  - The dynias.
AB  - The "dynias" are a group of chronic, focal pain syndromes with a predilection for
      the orocervical and urogenital regions. They include glossodynia, carotidynia,
      vulvodynia, orchidynia, prostatodynia, coccygodynia, and proctodynia. In some
      cases, the dynias occur secondarily, but more often, despite an exhaustive
      evaluation, no etiology is found and in these remaining cases, the cause of the
      pain remains enigmatic. The controversy that surrounds this group of disorders,
      which ranges from questioning their existence to suggesting that they are purely
      psychosomatic, is counterbalanced by an extensive literature attesting to their
      organicity. The approach to the patient begins with acknowledging that the
      symptom is well described, searching for a secondary cause, and performing a
      careful psychologic assessment. Treatment is empirical and patients can often be
      helped with medications used to treat neuropathic pain, all the while providing
      psychologic support and exercising caution toward invasive and irreversible
      therapeutic procedures.

PMID- 8879060
TI  - Pure motor hand weakness.

PMID- 8879061
TI  - The menagerie of migraine.
AB  - Migraine is conventionally regarded as a specific type of headache with a small
      set of associated neurologic symptoms. Yet, the true scope and frequency of
      migrainous phenomena are much greater than is generally acknowledged. Six cases
      are presented to illustrate some of the diverse manifestations of migraine: (1)
      transient global amnesia, (2) persistent visual phenomena, (3) migraine and
      seizures, (4) vestibular dysfunction, (5) hearing loss, and (6) migraine
      masquerading as multiple sclerosis. These and other migraine-associated
      neurologic symptoms are discussed in relation to previous reports in the
      literature. Pitfalls in recognizing the diverse manifestations of migraine, which
      are often underdiagnosed or misdiagnosed, are reviewed. Whether or not the
      established diagnostic criteria for migraine are too strict, other factors
      contributing to failure to identify migraine when it causes nonclassic neurologic
      symptoms include: (1) the belief that these are rare, (2) lack of an objective
      measure for migraine, (3) inadequate attention to the positive diagnostic
      features of migraine in the absence of headache, (4) confusion regarding prior
      migraine history, and (5) dismissing the diagnosis because of reported failure of
      prior migraine treatment. Recognition of the diversity of migraine helps avoid
      unnecessary testing and opens the door to effective treatment.

PMID- 8879062
TI  - Goldblatt's syndrome: relapsing-remitting amyotrophic lateral sclerosis.

PMID- 8879063
TI  - Taking stock of America's youth.
AB  - Approximately 40 million Americans are between the ages of 14 and 24. This age
      cohort currently represents about 15 percent of the total U.S. population.
      Members of this age group are developing their identities and experiencing
      occasional confrontation between generations. This period of development also
      includes education, training and job market testing. The direction these youths
      set out to follow will largely determine their course for much of their adult
      lives. A good start is therefore essential. Unfortunately, high school dropout
      rates are still very high and raise concerns about a widening economic gap
      between high income/low unemployment and low income/high unemployment members of
      society in an increasingly complex job world. The average income of young workers
      naturally tends to be low-a fact that belies the economic clout and future
      potential of this group. Every generation of young adults has left its mark on
      society as it passes through this stage of life, and the echo boomers--the
      offspring of the baby boomers--are certain to do just that.

PMID- 8879064
TI  - Current and future impact of rising multiple birth ratios on low birthweight.
AB  - Before 1980, multiple births with their increased risk of low birthweight
      comprised too small a proportion of births in the United States to have a
      significant impact on overall low birthweight levels; the recent steep rise in
      the multiple birth ratio has heightened their influence, however. Between 1980
      and 1992 the white multiple birth ratio rose from 18.5 to 24.0 multiple births
      per 1,000 births. While the overall level of white low birthweight newborns
      increased slightly between 1980 and 1992 (from 5.7 percent to 5.8 percent), low
      birthweight for white singletons actually improved, declining from 4.9 to 4.7
      percent. Thus, the increase in overall white low birthweight levels is a
      reflection of the increase in white multiple births and, to a much lesser extent,
      of the small increase in low birthweight among these births. Black multiple birth
      ratios and overall low birthweight also rose in this period. The black multiple
      birth ratio increased from 24.4 in 1980 to 28.2 per 1,000 births in 1992, and low
      birthweight rose from 12.7 to 13.3 percent. Although low birthweight for black
      singletons also increased (from 11.5 percent to 11.8 percent), the increase was
      at a slower pace than for all pluralities combined. Thus, for both white and
      black births, overall trends in low birthweight mask the disparate patterns of
      singleton and multiple births. It is, therefore, essential to examine low
      birthweight trends by plurality to assess accurately changes in this key
      indicator of infant health.

PMID- 8879065
TI  - Canadian population growth.
AB  - Although slowing recently, the population of Canada has rapidly increased since
      1986. These gains reversed a 25-year trend of progressively smaller intercensal
      increases, which were brought about by low levels of net in-migration and
      declining birth rates. Ontario, Canada's most populous province, is projected to
      have just over 11 million residents in 1995, which will be 37 percent of the
      country's entire population. Among other heavily populated areas, relative gains
      were much higher in British Columbia than in Quebec or Alberta. Analysis by age
      group revealed significant regional disparities. Compared to the national
      average. Alberta's residents were much younger while persons living in British
      Columbia were generally older. Nationally, the median age of the population rose
      to a record high of 33.5 years. Among Canada's 25 large metropolitan areas, only
      eight experienced double-digit gains between 1986 and 1991. In the two most
      populous regions, Toronto and Montreal, the population increased by 13.4 and 7.0
      percent, respectively.

PMID- 8879066
TI  - Average hospital charges for medical and surgical treatment of back problems:
      United States, 1993.
AB  - During 1993, more than 6,000 patients covered by MetLife group health contracts
      were hospitalized for the surgical or medical treatment of back pain. Among the
      3,480 patients aged 21 to 64 with surgically treated back problems, the total
      charge averaged $13,990, with just over half of this total attributed to the
      hospital charges. The average length of hospital stay was 3.1 days for these
      patients. Of the 2,529 nonsurgically treated patients with back problems aged 21
      to 64, the average charge totaled $7,120--approximately half the charges of the
      surgically treated patients. A full 90 percent of this total was accounted for by
      the hospital portion of the bill, which included an average length of stay of 4.1
      days. Of the states with at least 50 admissions, the total charges ranged from a
      high of $20,040 in California to a low of $10,070 in Washington State for
      patients with surgical back claims. Among the states with at least 50 admissions,
      the California total charge was also the highest for the medically treated back
      problem patients ($11,460), but the lowest total charge was registered in Indiana
      ($5,490). Total average hospital charges (room and board and ancillary fees) were
      $7,610 for the surgical back patients and $6,430 for the medically treated back
      patients. Ancillary fees were 84 and 73 percent of the hospital charges to
      insurance for surgical back and medical back claims, respectively. Physician fees
      averaged $6,380 for the surgical category and $690 for the medically treated
      group of patients.

PMID- 8879067
TI  - Effects of alcohol and prescription and over-the-counter drug use on liver enzyme
      profiles.
AB  - Liver function tests are commonly ordered during routine checkups or in an effort
      to identify the cause of underlying disease. Elevated liver enzymes usually
      indicate a disease or an insult to the liver, the main causes of which can be
      hepatitis (caused by virus infection or chemical exposures) or cirrhosis of the
      liver due to alcohol abuse. Results from the Metropolitan Life Insurance Testing
      Laboratory confirm national data showing a slow rise in the percentage of "free
      living" persons with elevated liver enzymes. The percentage of "abnormal" results
      increased despite unchanged analytic methods or quality control measures during
      the data gathering period. In addition, the proportions of abnormal enzyme levels
      have increased while U.S. per capita alcohol consumption has decreased and sales
      of over-the-counter medications that elevate liver enzymes have increased. Thus,
      it is increasingly more difficult to determine the true cause of elevated liver
      enzymes. As more Americans self-medicate and as more prescription drugs become
      available over-the-counter, which can have subtle or overt effects on liver
      enzyme secretion, the causes for abnormal enzyme levels will remain difficult to
      interpret. Continued monitoring of liver enzyme levels and the prevalence of drug
      and alcohol use are necessary to determine if the noted rise in abnormal levels
      is associated with increased morbidity or adverse outcome.

PMID- 8879068
TI  - The urgency of visits to hospital emergency departments: data from the National
      Hospital Ambulatory Medical Care Survey (NHAMCS), 1992.
AB  - During 1992, an estimated 89.8 million visits were made to the emergency
      departments (EDs) of nonfederal, short-stay or general hospitals in the United
      States. Of these ED visits, 40.1 million (44.6 percent) were labeled urgent by
      hospital staff. For survey purposes, an urgent visit was defined as one in which
      the patient requires immediate attention for an acute illness or injury that
      threatens life or function and where delay would be harmful to the patient.
      However, visits to hospital EDs, whether reported as urgent or nonurgent by
      hospital staff, may resemble each other in a number of ways. The
      "appropriateness" of an ED visit should not be equated solely with staff
      determinations of urgency, which are often made following evaluation and
      diagnosis rather than on the patient's presenting condition. Stomach pain was the
      reason most frequently given by patients for making an ED visit. These visits
      were reported by hospital staff to be urgent about half the time (47.5 percent of
      visits). The proportion of urgent visits for the most frequent reasons ranged
      from three-quarters of visits for chest pain and asthma to one-fifth of visits
      for throat symptoms and skin rash. About one-third of all ED visits (32.7
      percent) received principal diagnoses within the broad category of injury and
      poisoning; roughly half of these visits were considered urgent. Along with injury
      and poisoning, diseases of the respiratory system and "signs, symptoms, and ill
      defined conditions" accounted for the majority of both urgent and nonurgent ED
      visits. About one-quarter (24.9 percent) of urgent ED visits resulted in hospital
      admission. However, the most common disposition at both urgent and nonurgent ED
      visits was referral to another physician.

PMID- 8879069
TI  - On urgency and appropriateness.

PMID- 8879070
TI  - Average charges for cholecystectomy open and laparoscopic procedures, 1994.
AB  - Claims to Metropolitan Life Insurance Company by group health insureds and their
      dependents for an open cholecystectomy averaged $16,260 in 1994 versus $12,930
      for a laparoscopic cholecystectomy. Laparoscopic procedures accounted for 71.1
      percent of the cholecystectomies charged to MetLife in 1994, up slightly from the
      70 percent in 1992. The charges for the open procedure varied by almost twofold
      among the 10 study states with at least 25 open surgeries; similar between-states
      variation was also evident among the 16 states in which at least 50 laparoscopic
      surgeries were performed. Florida, Illinois, Louisiana, California and Texas each
      reported average total charges above the average for both procedures; whereas
      Ohio and New Jersey reported the lowest total charges for an open cholecystectomy
      and Ohio and Michigan had the lowest laparoscopic average total charges. Hospital
      charges accounted for 77 percent of the total charges for an open procedure and
      for 69 percent of the laparoscopic surgeries. For both forms of surgery this
      proportion was the lowest in New York (65 and 48 percent, respectively). Length
      of stay averaged 6.5 days for the open cholecystectomy and 3.1 days for the
      laparoscopic procedure.

PMID- 8879071
TI  - Probability of developing or dying of cancer United States, 1991.
AB  - Since the mid-1960s, the proportion of deaths from the leading cause of U.S.
      mortality, heart disease, has decreased fairly steadily. The proportion of cancer
      deaths has risen over the same period, however, from 16.3 percent in 1965 to 23.7
      in 1991. Public awareness of this increase has resulted in questions being raised
      about the probability of developing or dying of cancer. Analyses of published
      data in the 1973-1991 Surveillance, Epidemiology and End Results (SEER) program
      of the National Cancer Institute estimated a person's lifetime risk of developing
      or dying of cancer. The lifetime risk of developing cancer is 44.8 percent for
      men and 39.3 percent for women. For both sexes, the risk of dying of lung cancer
      is higher than for any other cancer.

PMID- 8879072
TI  - Epidemiology of coca derivatives use in the Andean region: a tale of five
      countries.
AB  - The countries of the Andean Region (Bolivia, Colombia, Ecuador, Peru, and
      Venezuela) have recently reported findings from drug use surveys. An integrated
      comparison of their results and the results from other countries is presented. A
      total of 24,108 people were surveyed. Lifetime prevalence of cocaine or coca
      paste use was between 0.8 and 3.0%. The highest prevalence of coca paste or
      cocaine use was found among individuals who were middle-age, middle-class, males,
      people who finished high school, those who had high income, and urban dwellers.
      The most frequent age of first use was 15 to 24 years. The study shows that coca
      and derivatives use is a public health problem that is affecting a productive
      segment of the population of this region.

PMID- 8879073
TI  - Service providers' perceptions of substance use self-help groups.
AB  - Using a two-stage Delphi procedure, an investigation was carried out into health
      and welfare professionals' knowledge of and relationship with self-help groups
      (SHGs). Professionals indicated that they perceived SHGs to be generally helpful
      for persons with substance use problems. Provision of social support was the most
      commonly perceived helpful aspect of SHGs, and unsuitability for some clients was
      the most commonly perceived unhelpful-aspect. Persons motivated to address their
      problems were those perceived to be most likely to find a SHG useful, with those
      not so motivated, or who deny their problem, being perceived to be least likely
      to find a SHG useful. Drug and alcohol user treatment specialists reported
      greater perceived failure of SHGs to address underlying psychopathology and
      greater perceived benefit for clients lacking social support. This may be of
      particular relevance for future attempts to investigate the process of recovery
      in SHGs.

PMID- 8879074
TI  - African-American women in an alcohol intervention group: addressing personal and
      political problems.
AB  - This paper describes a qualitative study in which African-American women met in a
      small group to discuss alcohol and drug problems. The goal was to expand the
      range of services available by creating an alternative intervention which
      provided a simultaneous focus on both the personal and the sociopolitical needs
      of Black women. Results suggest that the dual focus on individual and social
      issues, and the opportunity to simultaneously address racism, sexism, and
      classism in an African-American women-only alcohol recovery group was helpful.

PMID- 8879075
TI  - Tobacco, alcohol, and illicit drug use among Mexican-American and non-Hispanic
      white high school students.
AB  - This study examined the prevalence, age of initiation, and pattern of substance
      use among 1,617 Mexican-American and non-Hispanic White high school students
      residing within the same geographic community. Ethnic differences were present
      for current smoking, having used alcohol in the past month, "heavy drinking" per
      occasion, and ever used marijuana. Age of initiation of substance use and the
      pattern of use was similar for the two ethnic groups. Future research needs to
      determine if the progression of initiation represents a sequence of initiation,
      identify factors that influence movement along the sequence, and determine if
      there are ethnic differences.

PMID- 8879076
TI  - Racial differences in adolescent drug use: the impact of religion.
AB  - Contrary to popular stereotypes, current studies of adolescent populations
      suggest that Black teens are less likely to use illicit drugs than are White
      teens. This study investigates the extent to which differences in religiosity are
      responsible for racial differences in drug use. Using data from a national survey
      of United States high school seniors, our results indicate that religion does
      provide some protection from drug use by adolescents. However, religiosity has
      less of an impact on the drug use of Black adolescents, perhaps as a result of
      the diverse roles of the Black church.

PMID- 8879077
TI  - Subtypes of alcohol involvement and their relationships to exits from
      homelessness.
AB  - This study sought to ascertain the presence of meaningful subtypes of alcohol and
      other drug involvement among homeless persons. Subtypes were derived using factor
      analysis to determine dimensions underlying alcohol involvement and cluster
      analysis to create unique subtypes. The types with the highest level of alcohol
      or drug use had the longest period of continuous homelessness and were less
      likely to have exited from homelessness when reinterviewed 6 months later. The
      dimensions represent a more sophisticated framework for describing alcohol and
      drug involvement among homeless persons and may be useful for practitioners in
      conducting assessments, designing programs, and planning interventions.

PMID- 8879078
TI  - Pilot test results comparing the All Stars program with seventh grade D.A.R.E.:
      program integrity and mediating variable analysis.
AB  - A pilot test of a new program, All Stars, was completed. Four variables known
      from prior research to mediate high-risk behaviors were measured: 1) personal
      commitment to avoid participating in high-risk behaviors, 2) ideals incongruent
      with high-risk behaviors, 3) bonding with prosocial institutions, and 4)
      conventional beliefs about social norms regarding high-risk behaviors. Compared
      to students who received the seventh grade D.A.R.E. program, students' who
      received the All Stars program had significantly better outcomes on each
      mediator. All Stars students also gave superior ratings to the program and their
      involvement in it.

PMID- 8879079
TI  - Alcohol consumption by undergraduate students.
AB  - This study examines a prediction of alcohol consumption in a sample of 212
      undergraduate students at a university in Sydney. Data were collected using self
      administered questionnaires, given to students in Semesters one and two. During
      both semesters the college residents reported drinking significantly more alcohol
      than students living elsewhere, but during vacation the intake of the two groups
      was approximately equal. Higher alcohol consumption in Semester two was best
      predicted by higher Semester one intake, followed by more consumption by friends
      and higher parental occupation status. Female students residing on campus were
      those most likely to be drinking at hazardous levels. Results also indicated that
      a significant proportion of residential students were drinking at hazardous
      levels, and that prevention interventions may need to focus on changing the
      attitudes and behavior of the social group.

PMID- 8879080
TI  - Personal and environmental factors in relation to adjustment of offspring of
      alcoholics.
AB  - The purpose of the present study was to develop a causal model that explains how
      personal and family characteristics influence the well-being of adult children of
      alcoholics (ACOAs). The causal model was developed based on family systems
      theory, coping theory, social learning theory, and social support theory. Eight
      four ACOAs were tested in order to examine the fit of the model to the data by
      path analysis with LISREL VII. Results of the study suggested that the revised
      theoretical model presented good model fit to the data with .97 for goodness of
      fit index, .91 for adjusted goodness of fit index, .13 for root-mean-square
      residuals, and 11.94 for modification indices. Results of the study also showed
      that 1) ACOAs who are better able to perceive the availability of social supports
      tend to have lower emotional status; 2) ACOAs who are better able to perceive the
      availability of social supports have a tendency to have better adjustment; and 3)
      ACOAs who have higher emotional status have a tendency to be better adjusted in
      life.

PMID- 8879081
TI  - News media framing sets public opinion that drugs is the country's most important
      problem.
AB  - Responses by the public to the question of whether drugs was the United States'
      most important problem ranged from under 5% to over 60% during the 9 years from
      1985 to 1994. Time series analysis showed that changes in this opinion could be
      explained by the press describing drugs as a crisis. Other types of drug
      discussion contributed negligibly. In the reverse direction, public opinion about
      drugs was a weak but significant contributor to press coverage.

PMID- 8879082
TI  - The effect of an orientation-to-treatment group on the retention of alcoholics in
      outpatient treatment.
AB  - Seventy-five poor inner city alcoholics were exposed to a 1/2-hour videotape
      orienting them to treatment. When compared to a similar group that did not see
      the videotape, the orientation group attended more clinic sessions in the
      following month. A greater percentage of them made more than 10 visits, were
      still active after the month, and went on to inpatient rehabilitation. The
      orientation group is an effective, cost efficient way of increasing patient
      follow through with treatment.

PMID- 8879083
TI  - Substance use among incarcerated adolescents: associations with peer, parent, and
      community use of substances.
AB  - This study of incarcerated adolescents documents the number and proportion of
      incarcerated adolescents who use cigarettes, alcohol, and illegal drugs; examines
      substance use among the adolescents' peers, parents, and community members; and
      examines associations between incarcerated adolescents' use of substances and
      substance use by peers, parents, and community members. Questionnaire data
      indicated that substance use was common among incarcerated adolescents as well as
      among the adolescents' peers, parents, and community members. Logistic regression
      analyses revealed that, similar to patterns observed in the general population,
      peer substance use was the strongest predictor of substance use among
      incarcerated adolescents.

PMID- 8879084
TI  - The prevalence and motivating factors of adolescent smoking at a rural middle
      school in Taiwan.
AB  - The purpose of this survey is to study the prevalence and motivating factors of
      smoking among 1,372 students at a rural middle school in Taiwan. The prevalence
      of smokers for total, male, and female students is 5.7, 11.5, and 0.4%,
      respectively. Prevalence increased with age and grade among males, but no
      significant differences were found among females. Prevalence was higher among
      students from nuclear families than those from extended families (OR = 2.8, 95%
      C.I. 1.4-5.5). Prevalence was also higher among students from families with very
      strict parental control or very little parental control (OR = 4.25, 95% C.I. 2.24
      8.08). The majority (70-80%) began smoking during primary school. Smokers who had
      attempted abstinence in the past had a better understanding of the hazards of
      smoking and smoked less frequently and with lower average consumption (P < .05).
      For 60% of the students the first source of cigarettes was friends or classmates;
      only 22% bought them. Health education increased understanding of the hazards of
      smoking (OR = 2.2, 95% C.I. 1.10-4.45). In conclusion, the primary factors that
      affect adolescent smoking are age, family structure, abstinence experience,
      strictness of upbringing, family influence, peer pressure, and health education.

PMID- 8879085
TI  - Mechanism of teratogenic action of thalidomide.

PMID- 8879086
TI  - Dermatoglyphics in offspring of women given gamma globulin prophylaxis during
      pregnancy.
AB  - The fingertip dermatoglyphic patterns were studied in 93 infants whose mothers
      had been given gamma globulin (GG) prophylaxis against hepatitis on known
      gestational dates. The prevalence of infants with whorl patterns on 0-3
      fingertips and that of infants with ulnar loops on 9 or 10 fingertips were
      significantly higher (P < 0.02 and P = 0.01, respectively) in offspring of women
      given prophylaxis during the first 162 days of pregnancy than in those whose
      mothers received GG at a later stage of gestation. These findings were
      particularly prominent in infants who had been exposed to > or = 5 ml of GG in
      the first 162 days of gestation. In light of these observations, and of
      previously noted dermatoglyphic changes in offspring of women who had gestational
      prophylaxis against rubella, it appears that exogenous GG can influence the
      prenatal development of fingertip skin ridge patterns, and that this influence is
      responsive to the gestational timing and dosage of GG administered.

PMID- 8879087
TI  - Retinoic acid-induced embryopathy of the mouse inner ear.
AB  - Retinoic acid (RA) is an active metabolite of vitamin A that is teratogenic when
      present in excess during mammalian embryogenesis. We have investigated the effect
      of embryonic exposure to nonphysiological levels of all-trans RA on the
      development of the mouse inner ear. Dysmorphogenesis of both vestibular and
      auditory portions of the inner ear, and abnormal formation of the surrounding
      capsule are produced by exposure to teratogenic levels of RA at an embryonic age
      of 9 days (E9). There was no observable teratogenic effect of RA when
      administered at earlier (i.e., E7 or E8) or later (i.e., E10) stages of otic
      morphogenesis. We hypothesize that exposure to high levels of RA during a
      critical period of early otic morphogenesis interferes with the inductive tissue
      interactions required for inner ear development.

PMID- 8879088
TI  - The safety of fluoxetine during pregnancy and lactation.

PMID- 8879089
TI  - Review of the role of potential teratogens in the origin of human nonsyndromic
      oral clefts.
AB  - Oral clefts are common birth defects affecting approximately 1 every 1,000
      caucasian newborns. While many syndromes with cleft lip with or without cleft
      palate (CL/P) or with cleft palate (CP) are recognized, the majority of oral
      clefts fall into the category of "nonsyndromic oral clefts" and the etiology of
      this group remains incompletely understood. Investigators agree that oral clefts
      are multifactorial in origin, with both genetic and environmental factors in
      their etiology. While animal models have identified several teratogens for oral
      clefts, their precise relevance for humans remains unclear. The goal of this work
      is to review literature on environmental exposures potentially associated with
      non-syndromic oral clefts.

PMID- 8879090
TI  - Absence of correlation between transient cranial hemorrhages and congenital
      malformations following neural crest ablation in chicks.
AB  - Ablation of premigratory cardiac neural crest has been used to produce and study
      extensively a model of abnormal cardiovascular dysmorphology. Previous and
      continuing research in this laboratory concerns different aspects of the
      involvement of cranial neural crest in the development of cranial, cervical and
      cardiac tissues in chick embryos. Recently, we detected the occurrence of
      transient cranial hemorrhages 24-48 hr after the ablation of selected segments of
      premigratory cranial neural crest. Since one possible mechanism of action for
      certain teratogens involves nonreparable damage to a primordial embryonic tissue
      by an antecedent hemorrhage, the objective of this study was to determine which
      of three different neural crest ablations is associated with hemorrhages and
      whether subsequent congenital abnormalities were correlated with the ablation
      procedure and/or hemorrhage. Premigratory neural crest was ablated from 3
      different sites, designated cardiac, mesencephalic and trunk crest, respectively,
      of stage 8-10 chick embryos. Sham-operated embryos were controls. At 24, 30, and
      48 hr after ablation, each embryo was observed for the presence of hemorrhages.
      On incubation day 11 all the living embryos were killed, fixed, weighed, and
      analyzed for selected length measurements, developmental stage, and the types and
      rates of congenital abnormalities. Cardiac and mesencephalic ablation group
      embryos exhibited significant incidences of cranial hemorrhages and changes in
      many of the parameters analyzed. It was concluded that the cardiac and
      mesencephalic, but not the trunk neural crest ablations, produced significant
      changes in incubation day 11 embryos. However, there was no correlation between
      the abnormalities and the prior occurrence of the transient cranial hemorrhages.

PMID- 8879091
TI  - Improvement of lesion detectability by speckle reduction filtering: a
      quantitative study.
AB  - An objective measure (Lesion Signal-to-Noise Ratio) quantifying the detectability
      of lesions in echographic images was employed. This measure was used to determine
      the performance of digital speckle reduction filters, which were applied to
      computer simulated ultrasound B-mode images. One linear (mean filter) and two
      nonlinear filters (median and L2-mean filters) have been investigated. A
      comparison was made between fixed and adaptive versions of these filters. The
      influence of the size of the filter window on the Lesion Signal-to-Noise Ratio
      was systematically investigated. Also, the effect of the shape of the filter
      window is illustrated. The difference in performance of the linear and nonlinear
      filters was found to be small. Adaptive filters did not perform significantly
      better than fixed filters. The maximum improvement of lesion detectability was in
      the order of 40 percent. The choice of a correct window size was critical. For
      all types of filters, an optimum window size appeared to be present in the curves
      relating the Lesion Signal-to-Noise Ratio to this size.

PMID- 8879092
TI  - Application of neural networks for the classification of diffuse liver disease by
      quantitative echography.
AB  - Three different methods were investigated to determine their ability to detect
      and classify various categories of diffuse liver disease. A statistical method,
      i.e., discriminant analysis, a supervised neural network called backpropagation
      and a nonsupervised, self-organizing feature map were examined. The investigation
      was performed on the basis of a previously selected set of acoustic and image
      texture parameters. The limited number of patients was successfully extended by
      generating additional but independent data with identical statistical properties.
      The generated data were used for training and test sets. The final test was made
      with the original patient data as a validation set. It is concluded that neural
      networks are an attractive alternative to traditional statistical techniques when
      dealing with medical detection and classification tasks. Moreover, the use of
      generated data for training the networks and the discriminant classifier has been
      shown to be justified and profitable.

PMID- 8879093
TI  - Texture analysis of ultrasonic images of the prostate by means of co-occurrence
      matrices.
AB  - As speckle on ultrasonic B-scan may reveal information relative to tissue
      structure, the present work attempts to discriminate the various prostatic
      tissues (normal tissue, benign prostatic hypertrophy and cancer) by means of
      texture analysis. We select regions of interest by their homogeneous appearance.
      A pre-processing stage is required to obtain stationary samples. The method used
      measures the second-order statistics, namely co-occurrence matrices. Fairly good
      tissue signatures have been obtained with parameters derived from these matrices.
      Of 37 images processed, 78 percent of the samples were classified with success,
      which is a high score considering that the images cannot be discriminated
      visually. However, while such results are obtained when wide regions of interest
      are investigated (64 x 64 pixels), they are not as good with smaller sample
      sizes, i.e., when the pathological area is very small.

PMID- 8879094
TI  - Characterization of tissue microstructure scatterer distribution with spectral
      correlation.
AB  - Characterization of tissue microstructure from the backscattered ultrasound
      signal using the spectral autocorrelation (SAC) function provides information
      about the scatterer distribution in biological tissue. This paper demonstrates
      SAC capabilities in characterizing periodicities in A-scans due to regularity in
      the scatterer distribution. The A-scan is modelled as a cyclostationary signal,
      where the statistical parameters of the signal vary in time with single or
      multiple periodicities. This periodicity manifests itself as spectral peaks both
      in the power spectral density (PSD) and in the SAC. Periodicity in the PSD will
      produce a well defined dominant peak in the cepstrum, which has been used to
      determine the scatterer spacing. The relationship between the scatterer spacing
      and the spacing of the spectral peaks is established using a stochastic model of
      the echo-formation process from biological tissue. The distribution of the
      scatterers within the microstructure is modelled using a Gamma function, which
      offers a flexible method of simulating parametric regularity in the scatterer
      spacing. Simulations of the tissue microstructure for lower orders of regularity
      indicate that the SAC components reveal information about the scatterer spacing
      that are not seen in the PSD and the cepstrum. The echoformation process is
      tested by simulating microstructure of varying regularity and analyzing their
      effect on the SAC, PSD and cepstrum. Experimental validation of the simulation
      results are provided using in vivo scans of the breast and liver tissue that show
      the presence of significant spectral correlation components in the SAC.

PMID- 8879095
TI  - Variable density linear acoustic inverse problem.
AB  - The linear acoustic inverse problem is solved simultaneously for density (rho)
      and compressibility (kappa) using the basic ideas of diffraction tomography (DT).
      The key to solving this problem is to utilize frequency diversity to obtain the
      required independent measurements. The receivers are assumed to be in the far
      field of the object, and plane wave incidence is also assumed. The Born
      approximation is used to arrive at a relationship between the measured pressure
      field and two terms related to the spatial Fourier transform of the two unknowns,
      rho and kappa. The term involving compressibility corresponds to monopole
      scattering and that for density to dipole scattering. Measurements at several
      frequencies are used and a least squares problem is solved to reconstruct rho and
      kappa at the same time. It is observed that the low spatial frequencies in the
      spectra of rho and kappa produce inaccuracies in the results. Hence, a
      regularization method is devised to remove this problem. Several results are
      shown. Low contrast objects for which the above analysis holds are used to show
      that good reconstructions are obtained for both density and compressibility after
      regularization is applied.

PMID- 8879096
TI  - Vaccine induced immunologic memory for hepatitis B surface antigen: implications
      for policy on booster vaccination.
AB  - This paper reviews published literature on the long-term persistence of
      immunologic memory for HBsAg after a course of hepatitis B vaccine and the
      functional significance this has for policy on booster vaccination. Several
      studies have shown that vaccine induced antibody (anti-HBs) specific for the
      surface antigen (HBsAg) of hepatitis B virus (HBV) is protective at a serum
      concentration of 10 milli-International Units per milliliter (mIU ml-1). When
      acquired passively (e.g. from hepatitis B immune globulin), susceptibility to
      infection returns as antibody declines. However, vaccine induces active synthesis
      of anti-HBs accompanied by immunologic memory for HBsAg that affords ongoing
      protection independent of antibody. Persistent memory over periods of 5 years or
      more is evident from large, rapid increases in antibody following booster
      vaccination, even in subjects who have lost antibody. Complementary studies,
      using an in vitro enzyme linked immunosorbent assay (spot-ELISA), show that the
      number of memory B lymphocytes able to produce anti-HBs does not diminish as the
      level of antibody declines. That immunologic memory provides effective immunity
      is suggested by serologic studies over periods of 5 years or more of vaccinees
      frequently exposed to HBV. Although many failed to maintain at least 10 mIU ml-1
      of antibody, there have been very few clinically significant breakthrough
      infections. Thus, it appears unnecessary to give healthy vaccinees a booster
      vaccination when the level of anti-HBs falls below 10 mIU ml-1. Current studies
      suggest good retention of immunologic memory in healthy vaccinees over periods of
      5-12 years. While additional studies will better define the limits of this
      phenomenon, routine booster vaccination should not be needed to sustain
      immunologic memory and protection within 5 years and perhaps longer after the
      primary vaccination series.

PMID- 8879097
TI  - Interference assessment of yellow fever vaccine with the immune response to a
      single-dose inactivated hepatitis A vaccine (1440 EL.U.). A controlled study in
      adults.
AB  - The objective of this open, controlled clinical trial was to assess whether
      Yellow Fever (YF) vaccine would interfere with one single dose of an inactivated
      hepatitis A (HAV) vaccine 1440 El.U. when they are administered simultaneously.
      One hundred and ten healthy adults (24 +/- 4 years old, 65% females) were
      included and randomized to receive one single dose of HAV vaccine (Group 1) or
      HAV vaccine plus YF vaccine (Group 2). All subjects received a booster dose of
      HAV vaccine (month 6). Anti-HAV antibodies were measured (ELISA method) at
      screening and at months 1, 6 and 7. One month after the first inoculation, the
      seroconversion rates and geometric mean titers for anti-HAV were 98% and 275 mIU
      ml-1 in Group 1 and 100% and 239 mIU ml-1 in Group 2. After the booster dose all
      vaccinees had become seropositive. Administration of YF vaccine did not alter the
      safety profile of HAV vaccine. These results indicate that simultaneous
      administration of YF vaccine does not interfere with the immune response to HAV
      vaccine (1440 El.U.) in young healthy adults.

PMID- 8879099
TI  - Hepatitis A vaccine responses in HIV-positive persons with haemophilia.
AB  - The safety and immunogenicity of subcutaneously (s.c.) administered hepatitis A
      (HA) vaccine was evaluated in HIV positive and negative patients with haemophilia
      and healthy male controls. The vaccine was well tolerated. Seroconversion
      occurred among all controls after one dose of vaccine but was delayed among
      patients, particularly if HIV-positive-4 of 17 (24%) failed to respond to three
      doses of vaccine. Following the third dose of vaccine, geometric mean titres were
      significantly higher among controls (1354) than among HIV infected patients (204)
      (P < 0.05). Non-responders failed to develop an immune response following
      boosting with high titre vaccine. Patients with haemophilia may be vaccinated
      against HA s.c. but consideration should be given to ensuring that HIV-positive
      individuals with haemophilia and other immunosuppressed individuals should have
      their immune responses checked since additional booster doses or passive
      prophylaxis may be necessary in such individuals.

PMID- 8879098
TI  - Intranasal stimulation of long-lasting immunity against aerosol ricin challenge
      with ricin toxoid vaccine encapsulated in polymeric microspheres.
AB  - Intranasal (i.n.) immunization with ricin toxoid (RT) vaccine encapsulated in
      poly (lactide-co-glycolide) microspheres (RT-PLG-Ms) and poly (L-lactide)
      microspheres (RT-PLA-Ms) stimulated systemic and mucosal immune responses and
      protected mice from aerosolized ricin intoxication. High titers of anti-ricin
      IgG2a were stimulated in the serum of mice with one or two doses of RT-Ms 6 weeks
      postimmunization. However, in the lungs, no IgG2a or total IgG was elicited
      either with RT-Ms or with aqueous RT. At 6 weeks postimmunization, a single dose
      of the RT-Ms stimulated secretory IgA (sIgA) in the lungs of four of six mice,
      but a second immunizing dose did not enhance the stimulation. A single dose of
      aqueous RT vaccine failed to stimulate sIgA in the lungs, while, a second dose
      induced sIgA in 50% of the mice. One or two i.n. doses of RT-Ms protected most of
      the mice against lethal aerosol-delivered ricin toxin 6 weeks postimmunization.
      In contrast, protection was absent or marginal after one or two doses of aqueous
      RT vaccine. In both studies, the protection against lethal aerosol challenge was
      significantly better with one dose of RT-Ms than with two doses of aqueous
      vaccine, which may be attributed to the induction of sIgA in the lungs and the
      serum. Duration of the IgG2a and IgA in the serum, particularly that of IgG2a was
      much longer after the administration of RT-Ms than after the aqueous vaccine. The
      geometric mean IgG2a titers stimulated with two doses of RT-Ms remained high
      during 40 weeks postimmunization and were up to 25 times higher than the titers
      induced with aqueous RT vaccine. After 6 weeks, the IgG2a induced by two doses of
      aqueous vaccine was no longer detectable. Persistence of antibody response was
      predictive of efficacy. At 1 year postimmunization with two doses of RT-Ms, 100%
      of mice were protected against lethal ricin challenge. However, at the same time
      no protection was afforded by two doses of aqueous RT. The results of the present
      study consistently demonstrated the advantages of microencapsulated RT vaccine to
      stimulate effective and long-lasting protection by i.n. administration.

PMID- 8879100
TI  - No major outbreaks of pseudorabies virus in well-immunized sow herds.
AB  - In this study we quantified the transmission of pseudorabies virus (PRV) in well
      immunized sow herds in The Netherlands. In three herds, sows were tested for
      antibodies to gE of PRV every time after they had been transported to another
      barn (survey A). In 99 other herds, sows were tested simultaneously once or twice
      yearly (survey B). We observed six introductions in survey A and 53 in survey B.
      None of these introductions resulted in extensive spread of the virus. The
      reproduction ratio R, which is defined as the mean number of secondary infections
      caused by one infectious sow, was significantly less than one. We conclude that
      PRV can be eliminated from sow herds by vaccination.

PMID- 8879101
TI  - Influence of the parental virus strain on the virulence and immunogenicity of
      recombinant vaccinia viruses expressing HBV preS2-S protein or VZV glycoprotein
      I.
AB  - Five triple-plaque purified vaccinia virus (VV) lines generated from smallpox
      Sevac VARIE vaccine (strain Praha) and three VV virus lines similarly derived
      from Wyeth DRYVAX vaccine were used for preparation of recombinants expressing
      the hepatitis B virus preS2-S gene. The same five Praha-derived virus lines were
      used to construct recombinants expressing the varicella-zoster virus (VZV)
      glycoprotein I (gpI) gene. Recombinants and their parental viruses were tested
      for the residual neurovirulence in mice. The virus lines and the recombinants
      derived therefrom differed markedly in this respect. Immunization of mice
      resulted in high levels of anti-HBsAg antibodies only in the case of recombinants
      derived from the relatively virulent viruses. In contrast, the levels of VZVgpI
      antibodies in mice were similar with all VV-VZV recombinants irrespective of the
      virulence of the parental virus line.

PMID- 8879102
TI  - Construction and characterization of virG (icsA)-deleted Escherichia coli K12
      Shigella flexneri hybrid vaccine strains.
AB  - Human challenge studies with EcSf2a-2, an aroD deletion-attenuated Escherichia
      coli K12-Shigella flexneri hybrid vaccine expressing S. flexneri 2a somatic
      antigen and the invasive phenotype indicated that, at doses of 2 x 10(9)
      bacteria, EcSf2a-2 was immunogenic but also reactogenic and therefore not
      sufficiently attenuated. Two factors that may contribute to the residual
      reactogenicity are the spontaneous appearance of plaque-positive variants in the
      E. coli K12 recipient and the presence of the arg locus encoding enterotoxin or
      cytotoxin, transferred from S. flexneri 2a into the E. coli recipient. EcSf2a-3
      was derived from EcSf2a-2 by introducing a deletion in the virG gene, whose
      expression is required for plaque formation and keratoconjunctivitis in guinea
      pigs. EcSf2a-5 contains the same deletion in the E. coli-S. flexneri hybrid
      strain, 7921, but does not contain the arg locus. Lack of virG expression in
      these hybrid strains did not affect the immune response to LPS or the development
      of protective immunity in the guinea pig model.

PMID- 8879103
TI  - Cross-reactivity of Shigella flexneri serotype 2a O antigen antibodies following
      immunization or infection.
AB  - To study the cross-reactivity pattern of Shigella flexneri 2a O-antigen
      antibodies, sera from humans and monkeys challenged with S. flexneri 2a, and from
      humans and guinea pigs immunized with a recombinant vaccine expressing serotype
      2a O-antigen, were tested against a panel of lipopolysaccharide extracted from
      heterologous S. flexneri. Sera from the two groups of humans, who were volunteers
      in either a clinical challenge or vaccination study, showed similar patterns:
      cross-reactivity was more often seen with IgA antibodies, and these were mostly
      cross-reactive with serotype 2b, which shares the type II antigen, and serotypes
      1a, 5a, and Y, which share 4 or 3, 4 group antigen, with 2a. The majority of sera
      from immunized guinea pigs showed both IgG and IgA cross-reactivity with 1a, 5a,
      and Y, but not 2b. The majority of sera from challenged monkeys showed cross
      reactivity with almost all flexneri serotypes tested, with 1a, 2b, and Y being
      recognized most often, and the cross-reactive antibodies were more often IgG than
      IgA. These results show that either immunization or challenge with the 2a
      serotype induces cross-reactive antibodies which recognize similar subsets of
      heterologous serotypes, and suggest that it may be possible to design multivalent
      vaccines against S. flexneri.

PMID- 8879105
TI  - The binding of chimeric peptides to GM1 ganglioside enables induction of antibody
      responses after intranasal immunization.
AB  - With a model peptide, the neutralizing epitope 50-75 of cholera toxin B subunit,
      two chimeric peptides were constructed. A T-cell epitope, the 174-187 peptide
      from the G protein of the respiratory syncytial virus, was co-linearly
      synthesized at the amino-(174-50) or carboxyl-terminus (50-174) of the 50-75
      peptide. Although both chimeric peptides were equally immunogenic by the
      intraperitoneal route, the 50-174 peptide was more immunogenic than the 174-50
      peptide by the intranasal (i.n.) route. Both chimeric peptides inhibited the
      binding of cholera toxin B subunit to GM1 ganglioside with the 50-174 peptide
      being more effective inhibitor than the 174-50 peptide. In addition, an effective
      priming of the immune system was achieved after the i.n. administration of
      immunogens. The observed unresponsiveness after the i.n. co-immunization with the
      50-174 peptide and GM1 ganglioside emphasize the role of GM1 binding for the
      induction of an immune response after i.n. immunization.

PMID- 8879104
TI  - Production of recombinant SERA proteins of Plasmodium falciparum in Escherichia
      coli by using synthetic genes.
AB  - We expressed two regions of the serine repeat antigen (SERA) protein of
      Plasmodium falciparum in Escherichia coli by synthesizing the genes with a
      changed codon usage. One of the synthetic gene sequences encodes amino acid
      residues 17-382 (SE47') and the other encodes amino acid residues 586-802
      (SE50A). The products produced by the synthetic gene sequences in E. coli
      accounted for 15-30% of the total bacterial protein. Antisera against both the
      purified gene products prepared in rats inhibited malaria parasite growth in
      vitro. The anti-SE47' serum was significantly more inhibitory than the anti-SE50A
      serum. The described methods provide a large scale preparation of recombinant
      antigens for improving and producing malaria vaccine.

PMID- 8879106
TI  - Comparison of the efficacy of replication-defective adenovirus and Nyvac poxvirus
      as vaccine vectors in mice.
AB  - Adenovirus and poxvirus recombinant vectors are more and more used as live
      experimental vaccines. In order to compare the efficacy of these vectors to
      elicit serological response and protection against challenge, two recombinants
      carrying the same gene (pseudorabies virus gD) were used as experimental vaccines
      in mice, a permissive species to pseudorabies infection. Two routes were tested:
      intramuscular (i.m.) and intranasal (i.n.) in order to try to stimulate general
      and mucosal immune responses. Several doses ranging from 10(2.9) to 10(8.9)
      TCID50, depending on the vaccines were tested. The estimated log 10 (PD50) for
      the i.m. route were 7.1 +/- 0.2 for the adenovirus vector (Ad-gD), and 7.6 +/-
      0.2 for the Nyvac vector (vP900). For the i.n. route, log 10 (PD50) of Ad-gD was
      7.1 +/- 0.2, and was higher than 7.9 for vP900. While the adenovirus vector
      proved more efficient than the poxviral vector to elicit antibody response, only
      a slight difference was observed when comparing the survival times of animals
      after challenge. Adenovirus was found better only for the 10(7.9) TCID50 dose,
      when inoculated i.m. Intranasal vaccination appeared efficient only with the
      adenovirus vector for the TCID50 10(8.9) dose.

PMID- 8879107
TI  - The effect of hole diameter on the torsional mechanical properties of the equine
      third metacarpal bone.
AB  - The torsional monotonic structural material properties of equine metacarpi with
      or without, either a 5/16 inch or 3/8 inch diameter bicortical lateromedial
      middiaphyseal hole were assessed to determine the effect of a hole on metacarpal
      strength. Torsional stiffness was not significantly effected by the presence of a
      bicortical hole, whereas yield and failure angles, torques and energies of
      metacarpi with a hole were 51% to 97% of those of intact bones. Significant
      differences were not apparent for yield and failure mechanical properties between
      metacarpi with a 5/16 inch diameter hole and metacarpi with a 3/8 inch diameter
      hole; however, postyield mechanical properties were lower for metacarpi with a
      3/8 inch hole. Whereas some metacarpi with a 5/16 inch hole were capable of
      plastic deformation before failure, metacarpi with a 3/8 inch diameter hole
      appeared to have sufficient stress concentration to propagate complete fracture
      on structural yield.

PMID- 8879108
TI  - Treatment of traumatic separation of the auricular and annular cartilages without
      ablation: results in five dogs.
AB  - Five dogs were diagnosed as having unilateral separation of the otic cartilages
      (auricular and annular). Four dogs had sustained prior trauma (hit by a car).
      Clinical signs were typical of ear canal stenosis and included swelling at the
      base of the ear (n = 2), periotic fistulation (n = 2), head tilt toward the
      affected side (n = 2), and pain when opening the mouth (n = 1). Palpation
      revealed separation of the horizontal and vertical ear canals. Otoscopic findings
      included a shallow ear canal and a pseudotympanic membrane across the proximal
      end of the auricular cartilage. Findings at surgery confirmed the diagnosis of
      cartilage separation and included an exudate-filled horizontal ear canal and a
      blind-ending vertical ear canal. Surgical treatment involved isolating the distal
      end of the annular cartilage (horizontal ear canal), opening and evacuating the
      horizontal ear canal, and suturing the open end of the annular cartilage to the
      skin. The length of annular cartilage was variable among the dogs, although each
      dog had sufficient horizontal canal to appose skin to otic epithelium. The
      vertical ear canal was not surgically dissected or manipulated. The mean follow
      up period was 46 +/- 14 months (range, 31 to 68 months). All five dogs had patent
      horizontal ear canals when examined at the follow-up examination.

PMID- 8879110
TI  - Structural properties of interlocking nails, canine femora, and femur
      interlocking nail constructs.
AB  - Using standard material testing techniques (bending stiffness, torsional
      stiffness, and maximum torque to failure or yield torque), the structural
      properties of interlocking nails (IN), canine femora, and IN/femur constructs
      were determined. Specimens that were tested included: 6 and 8 mm diameter IN with
      5 to 10 screw holes (n = 18), and intact canine femora (n = 10), which also, with
      an IN inserted, formed the intact construct (IC) group, (n = 10). Specimens in
      the IC group were first tested with an 8 mm diameter IN with zero screws,
      followed by one and two screws (4.5 mm diameter) in the proximal and distal
      femur. A fracture model construct (FMC), (n = 14), consisting of a transverse
      femoral osteotomy with a 3 mm gap, was used with either 6 mm or 8 mm IN. In the 6
      mm FMC, one and two 3.5 mm screws were used sequentially in the proximal and
      distal femoral segment. In the 8 mm FMC, one and two 3.5 mm screws and one and
      two 4.5 diameter screws were used similarly. When bending forces were applied
      parallel to IN screw holes, mean IN stiffness was 20% less than with forces
      perpendicular to the holes (n = 18), (P < .05). Eight-millimeter IN were 220%
      stiffer in torsion and 270% stiffer in bending than 6 mm IN (P < .05). Six
      millimeter IN had approximately 32% of the bending stiffness and torsional
      stiffness of intact femurs (P < .05). Eight-millimeter IN had 93% and 79% of the
      bending stiffness and torsional stiffness, respectively, of intact femurs. Intact
      femur constructs (8 mm IN with four, 4.5 mm screws) had 147% of the bending
      stiffness (P < .05), and similar torsional stiffness and maximum torque, as
      intact femora (P > .05). The mean values of 6 mm FMC with four screws (3.5 mm)
      were 21% and 33% in torsional stiffness and bending stiffness, respectively, of
      intact femora values. When tested in torsion, 8 mm FMC failed by bone fracture; 6
      mm FMC, in contrast, underwent plastic deformation. In comparing FMC stabilized
      with an 8 mm IN with two screws (4.5 mm diameter) in each bone segment, to intact
      femurs, the maximum torque was similar, FMC torsional stiffness was 40% (P <
      .05), and FMC bending stiffness was 65% (P < .05). These 8 mm FMC percentages are
      comparable to human IN fracture model construct values, indicating that the 8 mm
      IN/four screw construct should provide adequate stabilization for many canine
      diaphyseal femoral fractures.

PMID- 8879109
TI  - Comparison of three methods for relief of pain after ear canal ablation in dogs.
AB  - This study compared three methods of pain relief in dogs that had total ear canal
      ablation with lateral bulla osteotomy. The hypothesis was that systemic opioids
      with preoperative local nerve blocks would provide superior pain relief. Thirty
      one dogs with chronic otitis externa were included in the study. Dogs were
      randomly assigned to one of three protocols: systemic opioids alone (10 dogs,
      group 1), systemic opioids with bupivacaine splash block (11 dogs, group 2), and
      systemic opioids with preoperative local bupivacaine nerve blocks (10 dogs, group
      3). Twenty-one dogs had bilateral ear ablation and 10 had unilateral ablation.
      Pain was assessed preoperatively, at extubation, 2 hours postextubation, and 1
      day postoperatively by a single observer blinded to the analgesic protocol used.
      Pain scores were not significantly different within or between groups, nor did
      unilateral versus bilateral ablation have a significant effect on the score. Mean
      scores were less than 3 (scale 1 to 5) for all groups at all observation times.
      Rough recoveries were noted in 30% of group 1 dogs, 0% of group 2, and 20% of
      group 3 dogs. Ninety-four percent of dogs were moderately to heavily sedated at
      extubation. Sixty percent of group 3 dogs remained moderately to heavily sedated
      2 hours postextubation. Rectal temperature, pulse rate, respiratory rate, and
      postoperative change in serum cortisol levels were not significantly different
      between groups. Postoperative increase in blood glucose was significantly higher
      in groups 1 and 3 compared with preoperative levels. Twenty-three percent of the
      dogs required additional analgesia or tranquilization after surgery, as
      determined by the anesthetist; 1 dog in group 1, 2 in group 2, and 4 in group 3.
      Each of the three analgesic protocols provided similar pain relief in dogs
      undergoing total ear canal ablation.

PMID- 8879111
TI  - Early experience with the use of an interlocking nail for the repair of canine
      femoral shaft fractures.
AB  - Static locked nailing was used to repair fractures of the femoral diaphysis in 15
      dogs. The implant consists of a 5, 6, or 7 mm diameter stainless steel rod made
      up of two parts: the body of the nail, in which there are 13 threaded holes, and
      a piece without holes that contains a slot for anchoring the jig. Good limb
      function was obtained after less than 3 weeks in 12 dogs and these dogs remained
      sound throughout the study. Radiographic examination revealed fracture healing in
      11 of the dogs, between 8 and 16 weeks after surgery. One dog was not returned
      for follow-up evaluation until 22 weeks after surgery; complete healing was
      apparent from radiographic examination. The remaining three dogs had to have
      additional operations, one because of lameness caused by excessive length of the
      distal screws, one because of a nonunion, and the third because of a sequestrum.
      Fracture healing in these dogs was observed at 18, 21, and 24 weeks respectively.
      Loosening of one screw and angulation of the bone occurred in one dog. These
      complications had no adverse effects on clinical outcome.

PMID- 8879113
TI  - Laparoscopic repair of scrotal hernia in two foals.
AB  - Nonstrangulating indirect scrotal hernias were corrected in two 4-week-old
      Percheron foals by a laparoscopic technique. After laparoscopic reduction of
      herniated nonstrangulated small intestine each testes was retracted through the
      vaginal ring. The ligament of the tail of the epididymis was transected by
      electrocautery. The testicular vessels and nerves were isolated by cautery of the
      mesenteric portion of the mesorchium and then ligated. Staples were used to close
      the opening of the inguinal canal by apposing the peritoneal edges of the vaginal
      ring. Resection of umbilical stalk remnants via celiotomy performed in one foal
      after laparoscopic observation of enlargement of the right umbilical artery and
      urachus. No complications or recurrence of herniation had occurred 16 weeks after
      surgery.

PMID- 8879112
TI  - A method for controlling portal pressure after attenuation of intrahepatic
      portacaval shunts.
AB  - Two dogs had right divisional intrahepatic portacaval shunts within the right
      lateral lobe of the liver. In both dogs, an extrahepatic portacaval vascular
      anastomosis was created, using an autologous right external jugular vein graft.
      The intrahepatic shunts were completely attenuated using a prehepatic
      intravascular caval approach. The creation of the vascular graft allowed
      postattenuation rises in portal pressure to be controlled, preventing the
      development of life threatening portal hypertension. Both dogs recovered from the
      procedure. One dog is clinically normal and does not require medication (8 months
      postoperatively); the other dog was euthanatized 5 months after surgery because
      of renal failure. Scintigraphy studies, performed before surgery, showed
      significant shunting of portal blood away from the liver (shunt indices 65% and
      59%), whereas, similar studies done 4 weeks afterwards showed almost normal
      portal blood flow (shunt indices 16% and 18%, respectively).

PMID- 8879114
TI  - Cephalad distribution of three differing volumes of new methylene blue injected
      into the epidural space in adult goats.
AB  - Epidural anesthesia and analgesia are popular regional anesthetic techniques in
      many animal species. However, we have not found any reports of studies in animals
      that have investigated the extent of cephalad migration and level of sensory
      blockade achieved based only on the volume of drug injected into the epidural
      space. The purpose of this study was to determine if there is a relationship
      between the volume (mL/kg) of an injectate injected epidurally and the extent of
      its cephalad migration within the epidural space. Twelve adult goats were
      randomly assigned to three treatment groups based on the volume of 0.12% New
      Methylene Blue (NMB), 0.1, 0.2, or 0.3 mL/kg, injected into the epidural space.
      The site and speed of injection, animal position, and direction of needle bevel
      were held constant. All injections were performed at the lumbo-sacral space
      immediately following euthanasia. At necropsy, the vertebral columns were
      transected longitudinally. The extent of cephalad migration of dye within the
      epidural space was easily determined by staining of the dura. Measurements were
      rounded to the nearest intervertebral space to which the dye had migrated. The
      individual making assessments was blinded to all treatments. In goats treated
      with 0.1, 0.2, or 0.3 mL/kg NMB, the number of stained spinal segments was 3.5 +/
      0.6, 6.5 +/- 0.9, and 8.8 +/- 0.6, (mean +/- SEM), respectively. Linear
      regression performed on the data was significant (P < .05) with R2 = 0.86. There
      was a strong linear relationship between volume (mL/kg) of epidurally injected
      NMB and cranial migration, with the larger volumes producing more cephalad spread
      within the epidural space. These results provide evidence for the volume of
      epidural injectate needed to produce a desired level of sensory blockade in adult
      goats.

PMID- 8879115
TI  - Intracellular membrane proliferation in E. coli induced by foot-and-mouth disease
      virus 3A gene products.
AB  - During picornavirus infection replication of genomic RNA occurs in membrane
      associated ribonucleoprotein complexes. These replication complexes contain
      different nonstructural viral proteins with mostly unknown function. To examine
      the function of nonstructural picornaviral proteins in more detail, cDNA of foot
      and-mouth-disease virus (FMDV) strain O1 Lausanne was cloned into lambda ZAP II,
      and different parts of the P3-coding sequence were expressed in E. coli by the T7
      polymerase system. Expression products constituted (a) fusion proteins composed
      of N-terminal leader peptide of bacteriophage T7 phi 10 protein fused to FMDV P3
      sequences of different lengths, (b) translation products of authentic P3-region
      genes, and (c) carboxy-terminally truncated 3A proteins. Expression products were
      characterized by NaDodSO4-polyacrylamide gel electrophoresis, immunoblotting, as
      well as electron and immunoelectron microscopy. We show here that in the T7
      polymerase system a high level of expression of 3A-containing peptides is
      achieved in E. coli. Remarkably, the expression of 3A-derived proteins induced a
      dramatic intracellular membrane proliferation in E. coli cells, similar to the
      vesicle induction observed in FMDV-infected cells. By immunoelectron microscopy,
      3A-reactive material was found associated with these membranes. We hypothesize
      that the FMDV 3A protein is instrumental in eliciting intracellular membrane
      proliferation in infected cells as a prerequisite for viral RNA replication.

PMID- 8879117
TI  - Functional analysis of simian immunodeficiency virus SIVAGM long terminal repeat.
AB  - We have previously shown that long terminal repeats (LTRs) derived from various
      isolates of SIVAGM share a unique functional property. In the absence of viral
      Tat, all SIVAGM LTRs act as much more efficient promoters than any of the other
      LTRs derived from representative primate immunodeficiency viruses. In the
      presence of Tat, however, SIVAGM LTRs are activated relatively inefficiently. To
      map the elements that confer these features on the SIVAGM LTR, a number of
      deletion mutants were constructed, and their promoter activities were determined
      using a bacterial CAT gene as a marker. The results obtained indicated that
      various elements located in the U3 region may contribute to the high basal
      promoter activity and that no negative elements are present in the region. The
      Tat-responsive sequence TAR was localized to the R region as observed for the
      other LTRs. A mutant carrying a single nucleotide deletion in this region
      completely lost responsiveness to Tat protein.

PMID- 8879116
TI  - Three-exon structure of the gene encoding the rat prion protein and its
      expression in tissues.
AB  - The prion protein (PrP), encoded by a chromosomal gene, is associated with
      development of the neurodegeneration of prion-induced diseases. Since
      determination of the complete structure of the gene encoding PrP is important for
      understanding gene expression in the central nervous system (CNS), the nucleotide
      (nt) sequence of the isolated whole gene encoding rat PrP (raPrP) was determined.
      The rat PrP gene (raPrP) spans 16 kilobases (kb) of the rat genome and contains
      three exons of 19-47 base pairs (bp), 98 bp, and 2 kb separated by two introns of
      2.2 kb and 11 kb. The first and second exons are noncoding, while the third exon
      contains a short 5' untranslated region, the entire 762-bp open reading frame
      (ORF), and a 3' untranslated region. The putative raPrP promoter in the 5'
      flanking region contains putative Sp1, AP-1, and AP-2 binding sites without a
      consensus TATA box. This TATA box-deficient feature, coupled with the presence of
      a high G+C content and Sp1-binding sites in the raPrP promoter, characterizes it
      as a housekeeping gene. Analysis of the raPrP cDNA 5'-end showed that raPrP mRNA
      transcription was initiated at multiple sites. Northern blot analysis showed that
      the levels of raPrP mRNA varied among rat tissues, with the highest levels found
      in the brain and placenta. This determination of raPrP nt sequences, including
      the introns and the 5' and 3' flanking regions, may make it possible to elucidate
      cis-acting elements that regulate the expression of this gene in different
      tissues and cell lines.

PMID- 8879118
TI  - E7 proteins of four groups of human papillomaviruses, irrespective of their
      tissue tropism or cancer association, possess the ability to transactivate
      transcriptional promoters E2F site dependently.
AB  - In an experimental system in which an expression vector including the E7 gene of
      a given human papillomavirus (HPV), together with a luciferase reporter plasmid
      including the adenovirus E2 (Ad E2) promoter, was transiently transfected into
      cultured mouse NIH3T3 fibroblastic cells, we obtained the signal indicating that
      E7 proteins of HPV type 5, 12, 14, 20, 21, 25, and 47, which are associated with
      epidermodysplasia verruciformis (EV), can transactivate the Ad E2 promoter, as
      previously reported for E7 proteins of other HPVs. Because the underlying
      mechanism of the transactivation had not been analyzed, except for
      transactivation by E7 gene of cervical cancer-associated HPV-16, we compared the
      E7 genes of representatives of three other groups of HPVs (HPV-1, -11, and -47)
      with that of HPV-16 with regard to their transactivating activity toward
      artificially constructed promoters. The experiment with a shortened AdE2 promoter
      carrying only the E2F sites and TATA box provided evidence that all four E7
      proteins can transactivate the shortened promoter and that this phenomenon is E2F
      site dependent. Further experiments with the reporter gene constructs carrying
      basal promoters or more complex forms with or without linked E2F sites, (a)
      confirmed previous finding by others that in cells producing no transactivator,
      the transcriptional level from promoters linked to E2F sites is rather repressed
      in comparison with the level of the corresponding promoters that are not linked
      to the E2F sites, and (b) demonstrated, for the first time, that in cells
      expected to produce the E7 protein of any one of the four HPVs, transcription
      from the promoter linked to the E2F sites was released from repression. In other
      words, the present results reveal that E7 proteins of any of the four HPVs can
      remove the E2F site-dependent repression, probably by modulating E2F complexes
      from repressing forms to activating ones.

PMID- 8879119
TI  - Presence of a hypervariable region within the hr2 domain of the host range
      determining sequences of the envelope protein gp85 (SU) of subgroup-A avian
      sarcoma-leukosis viruses.
AB  - The nucleotide sequence of the gene for the envelope protein gp85 (SU) of the
      Schmidt-Ruppin subgroup A (NY) strain of Rous sarcoma virus [SRA(NY)] was
      determined, and the deduced amino acid sequence was compared with those of other
      avian sarcoma-leukosis viruses. Among the five host-range determinant sequences
      (vr1, vr2, hr1, hr2, and vr3), the host-range determinant sequence hr2 of SRA(NY)
      showed a significant deviation from the hr2 sequences of other subgroup A viruses
      namely, RAV-1 and SRA(SF). A phylogenetic analysis of the amino acid sequence of
      this region indicated that this intra-subgroup diversity was as great as or even
      greater than the inter-subgroup diversity found among other subgroups of ASLV.
      Within the hr2 region, we found a short hypervariable segment that differs in
      length and sequence from hr2 of other subgroup-A viruses. The difference in the
      hr2 amino acid sequence between SRA(NY) and SRA(SF) is reflected in the predicted
      protein secondary structure of this region.

PMID- 8879120
TI  - High prevalence of adeno-associated virus (AAV) type 2 rep DNA in cervical
      materials: AAV may be sexually transmitted.
AB  - Adeno-associated virus (AAV) is a human parvovirus that in laboratory and animal
      models has the ability to suppress the oncogenic phenotype of a variety of
      viruses and cellular derived oncogenes. The inhibitory effects of AAV have been
      mapped to its rap gene (Rep78 protein). Furthermore, seroepidemiologic data
      indicate that AAV infection is linked to reduced cervical cancer rates in humans.
      Because of AAV's inverse relationship with cervical cancer, we attempted to
      identify AAV rep sequences within DNA derived from cervical brushings taken from
      nondiseased middle class patients at a Little Rock clinic. Polymerase chain
      reaction (PCR) amplification was carried out with primers designed to amplify a
      specific segment of the endogenous human beta-globin gene or the AAV rep gene. Of
      those cervical samples that were positive for beta-globin DNA, 50% were also
      found to be positive for AAV rep DNA when analyzed by either ethidium bromide
      staining or dot-blot hybridization with an internal probe. These data strongly
      suggest that AAV is commonly carried in the genital region and further raise the
      possibility that AAV can be sexually transmitted.

PMID- 8879121
TI  - Localization of hepatitis B virus core protein and viral DNA at the nuclear
      membrane.
AB  - An early step in the replication of the hepatitis B virus (HBV) genome is the
      transport of the viral DNA into the nucleus of the infected cell. So far only
      little is known about the events and mechanisms at the nuclear membrane required
      for entry of the viral genome into the nucleus. Using a hepatoblastoma cell line
      that constitutively produces hepatitis B virions and in so doing displays
      intracellular viral amplification, we showed that nonparticulated HBV core
      protein is associated with nuclear membrane pore complexes. Additionally, viral
      DNA has been detected firmly attached to the nuclear membrane. Small amounts of
      viral core protein, as well as viral DNA, were detectable within the cell
      nucleus. However, core particles could not be shown at the nuclear membrane or
      within the nuclei of these cells. Our observations on localization of HBV DNA and
      core protein at the nuclear membrane thus provide a suggestion for further
      examinations of the transfer of the viral genome from the cytoplasm into the
      nucleus of the infected cell.

PMID- 8879122
TI  - Human adenovirus type 5 variants with sequence alterations flanking the E2A gene:
      effects on E2 expression and DNA replication.
AB  - The human adenovirus type 5 (Ad5) E2 transcription unit is divided into a
      promoter-proximal region, E2A, and a distal region, E2B, each with its own
      polyadenylation site. Together these regions encode the three virus-derived
      proteins necessary for genome replication. Ad5 variants were produced that
      carried linker insertion mutations immediately 5' and/or 3' to the coding
      sequence for the E2A gene DNA binding protein (DBP). Two variants carrying solely
      a 5' lesion showed decreased usage of the adjacent 3' splice site, via which the
      DBP mRNA is produced, and an increased usage of the alternative downstream splice
      sites in the E2B region, wherein viral DNA polymerase and terminal protein
      precursor are encoded; these viruses showed somewhat reduced growth. A variant
      carrying a 3' lesion showed a marginal increase in DBP expression and slightly
      accelerated growth. When lesions 5' and 3' to the DBP coding sequence were
      combined in cis, the resulting virus was severely defective for growth and
      expressed E2B products to the virtual exclusion of E2A DBP. These data indicate
      that interactions must occur between the E2A 3' splice site and polyadenylation
      site before this region can be treated as an exon by the RNA processing
      machinery, and that a sequence alteration at the polyadenylation site that alone
      has only minor effects on the pattern of RNA processing can drastically affect
      terminal exon usage when placed in cis with a mutation that reduces splicing
      efficiency at the upstream 3' splice site. The data further indicate that, in
      vivo, Ad5 DNA replication is limited by prevailing DBP levels rather than by
      levels of polymerase or terminal protein precursor.

PMID- 8879123
TI  - An Arg-Lys insertion at the hemagglutinin cleavage site of an H5N2 avian
      influenza isolate.
AB  - Recent isolations of H5N2 subtype avian influenza (AI) viruses in North America
      have raised questions concerning their origin, transmission to commercial
      poultry, and potential for virulence. One ratite-origin isolate of low
      pathogenicity, A/emu/TX/39924/93 (H5N2), was subjected to a procedure that
      rapidly selects and/or amplifies highly pathogenic (HP) strains. The resulting
      highly virulent derivative had an altered hemagglutinin (HA) gene containing an
      additional six nucleotides at position 970-975 in the HA1 coding region. This
      resulted in an arg-lys insertion near the proteolytic cleavage site of the HA
      protein. The remainder of the HA sequence differed by an additional seven amino
      acids from the parent. The HA precursor of the derivative, but not the parent,
      was readily cleaved during replication in cell culture without addition of
      trypsin. In experimentally infected chickens, the derivative produced lesions
      typical of highly pathogenic avian influenza. A reverse transcriptase-polymerase
      chain reaction (RT-PCR) primer set was designed to amplify exclusively from
      molecules with the inserted six nucleotides. The set yielded product only from
      the selected derivative samples and not the parent. Thus, the levels of the HP
      variants in the parent stock were undetectable, or the insertion occurred rapidly
      during the selection process.

PMID- 8879124
TI  - Nucleotide sequences of the M gene of prevailing wild measles viruses and a
      comparison with subacute sclerosing panencephalitis virus.
AB  - We determined the nucleotide sequences of the coding region for the M gene in
      seven strains of measles virus (MV) that were isolated in Japan between 1984 and
      1993. The mutation found among the seven differed from those of laboratory
      strains. Many of these mutations were the same as those that are characteristic
      of SSPE viruses. Thus, we suggest that the mutations that have been considered
      specific to SSPE virus are in fact consensus among prevailing MV.

PMID- 8879126
TI  - Identification of structural similarities between putative transmission proteins
      of Polymyxa and Spongospora transmitted bymoviruses and furoviruses.
AB  - Comparison of amino acid sequence and hydropathy profiles shows conserved,
      structural similarities between the capsid readthrough protein of potato mop top
      virus (transmitted by Spongospora subterranea) and furovirus and bymovirus
      proteins implicated in transmission by Polymyxa spp. This suggests that these
      proteins have a common ancestry and are involved in a common biological process:
      virus transmission by plasmodiophorid fungi.

PMID- 8879125
TI  - Host-range restriction of vaccinia virus E3L-specific deletion mutants.
AB  - The vaccinia virus (VV) E3L gene product functions as a dsRNA binding protein
      that is involved in conferring an interferon-resistant phenotype upon the virus.
      Studies with a vaccinia virus (VV) E3L- deletion mutant (vP1080) have also
      demonstrated that the E3L gene product is critical for productive replication on
      certain cell substrates. While E3L was found to be nonessential for replication
      in chick embryo fibroblasts (CEFs), virus specifically deleted of E3L was found
      to be replication deficient in Vero, HeLa, and murine L929 cells. Further, the
      temporal block in replication appears to differ in these cell systems, as
      evidenced by the observed timing of protein synthesis inhibition. In Vero cells
      infected with the VV E3L- mutant, there was no detectable protein synthesis after
      2 hr post-infection, whereas in L929 cells normal protein patterns were observed
      even at late times post-infection. Expression of a heterologous dsRNA binding
      protein, the reovirus sigma 3 protein, by the E3L- mutant virus restored near
      wild-type growth characteristics, suggesting the critical nature for regulating
      dsRNA levels in VV-infected cells.

PMID- 8879127
TI  - A genomic map of infectious laryngotracheitis virus and the sequence and
      organization of genes present in the unique short and flanking regions.
AB  - We present a genomic map of infectious laryngotracheitis virus (ILT) and an
      18,912 bp sequence containing the entire unique short region and a portion of the
      flanking short repeats. In determining the genomic map, an 856 bp region repeated
      as many as 13 times was identified within the short repeats. The unique short
      sequence contains nine potential open reading frames (ORFs). Six of these ORFs
      show homology to other known herpesvirus unique short genes. Using the herpes
      simplex virus nomenclature, these genes are the US2, protein kinase, and
      glycoproteins G, D, I, and E (ORF 1, 2, 4, 6, 7, and 8, respectively).
      Interestingly, an open reading frame with homology to HSV-1 UL47 (ORF 3) is found
      in the unique short. One very large open reading frame (ORF 5) is present and
      contains a threonine-rich, degenerate repeat sequence. This gene appears to be
      unique to ILT among sequenced herpesviruses. Two ORFs were identified within the
      short repeat (SR) region. SRORF 1 is homologous to a gene (SORF3) found in the
      unique short region in both MDV and HVT, and appears to be specific to avian
      herpesviruses. SRORF 2 has homology to HSV US10.

PMID- 8879128
TI  - High susceptibility of U937-derived subclones to human immunodeficiency virus
      type 1 infection correlates with accumulation of unintegrated circular viral DNA.
AB  - Our previous report showed that U937-derived subclones were differentiated into
      at least three types (high, middle, and low types), even in the subclones
      expressing similar levels of surface CD4, in terms of the kinetics of the
      appearance of viral antigens and virus production after infection with human
      immunodeficiency virus type 1 (HIV-1). Here we showed the evidence that high
      susceptibility to HIV-1 infection, which was confirmed by the profound expression
      of viral messages and antigens, was exclusively associated with a high number of
      the unintegrated extrachromosomal form of viral DNA, but not with the amounts of
      adsorbed virus RNA nor those of integrated DNA form. The difference in the
      amounts of extrachromosomal form of viral DNA was also observed in the culture
      with 3'-azido-3'-deoxythymidine (AZT), indicating that the susceptibility is
      essentially unrelated to multiple infection events. Thus, the susceptibility of
      U937-derived subclones to HIV-1 infection seems to be affected by the occurrence
      of specific events involved in the accumulation of unintegrated viral DNA after
      viral adsorption.

PMID- 8879129
TI  - Sequence of echinochloa hoja blanca tenuivirus RNA-5.
AB  - The sequence is presented of RNA-5 of Echinochloa hoja blanca tenuivirus, a
      second tenuivirus associated with rice cultivation in Latin America (after rice
      hoja blanca virus). The RNA is 1334 nucleotides long and contains in the
      complementary sense RNA a single long open reading frame. The deduced amino acid
      sequence of this open reading frame shows that it encodes a highly basic and
      hydrophilic 44 kD protein (pc5) with about 50% similarity to the pc5 protein of
      maize stripe virus (MStV). This and other features of the RNA are discussed.

PMID- 8879130
TI  - A common structural core in the internal ribosome entry sites of picornavirus,
      hepatitis C virus, and pestivirus.
AB  - Cap-independent translations of viral RNAs of enteroviruses and rhinoviruses,
      cardioviruses and aphthoviruses, hepatitis A and C viruses (HAV and HCV), and
      pestivirus are initiated by the direct binding of 40S ribosomal subunits to a cis
      acting genetic element termed the internal ribosome entry site (IRES) or ribosome
      landing pad (RLP) in the 5' noncoding region (5'NCR). RNA higher ordered
      structure models for these IRES elements were derived by a combined approach
      using thermodynamic RNA folding, Monte Carlo simulation, and phylogenetic
      comparative analysis. The structural differences among the three groups of
      picornaviruses arise not only from point mutations, but also from the addition or
      deletion of structural domains. However, a common core can be identified in the
      proposed structural models of these IRES elements from enteroviruses and
      rhinoviruses, cardioviruses and aphthoviruses, and HAV. The common structural
      core identified within the picornavirus IRES is also conserved in the 5'NCR of
      the divergent viruses, HCV, and pestiviruses. Furthermore, the proposed
      structural motif shares a structural feature similar to that observed in the
      catalytic core of the group 1 intron. The conserved structural motif from these
      divergent sequences that looks like the common core region of group 1 introns is
      probably a crucial element involved in the IRES-dependent translation.

PMID- 8879131
TI  - Molecular cloning and sequence determination of the complete genome of the
      virulent echovirus 9 strain barty.
AB  - As part of a study of the molecular basis of pathogenicity of echovirus 9, the
      complete nucleotide sequence of the mouse-virulent echovirus 9 strain Barty was
      determined. Excluding the poly(A) tail, the complete RNA genome is composed of
      7451 bases. The postulated open reading frame extends from nucleotide (nt) 741 to
      7349 and predicts a polyprotein of 2203 amino acids (aa). As compared with the
      sequence of the echovirus 9 prototype strain Hill, which is apathogenic for
      newborn mice, 1492 nt are exchanged, leading to 9% divergence of the deduced
      amino acid sequence. The foremost difference between both strains is located at
      the C-terminus of the capsid protein VP1. In the case of strain Barty, an
      additional 10 aa fragment, including an RGD motif, is inserted.

PMID- 8879132
TI  - Molecular dissection of influenza virus RNA polymerase: PB1 subunit alone is able
      to catalyze RNA synthesis.
AB  - Influenza virus RNA polymerase with the subunit structure PB1-PB2-PA is involved
      in both transcription and replication of the RNA genome. Enzyme reconstitution
      experiments indicated that all three P proteins are required for RNA synthesis in
      vitro (Kobayashi, et al. Virus Res 22, 235-245, 1992). Nuclear extracts of HeLa
      cells infected with three kinds of the recombinant vaccinia virus, each carrying
      one of the three P protein cDNAs, exhibited the activity of complete replication,
      that is, vRNA-sense RNA-directed and cRNA-sense RNA-directed RNA synthesis in the
      absence of primers. The nuclear extract from cells singly infected with the virus
      carrying PB1 cDNA exhibited a significant level of model v-sense RNA-directed RNA
      synthesis activity. Thus we conclude that PB1 is the catalytic subunit of
      influenza virus RNA polymerase and that under certain conditions, PB1 alone is
      able to catalyze RNA synthesis in vitro.

PMID- 8879133
TI  - Characterization of human papillomavirus type 57b: transforming activity and
      comparative sequence analysis as probes for biological determinants associated
      with high-risk oncogenic viruses.
AB  - The association of human papillomavirus type 57 (HPV-57) with premalignant and
      malignant tumors of the nasal cavity was previously reported (Wu et al., Lancet
      341, 522, 1993). We determined the complete nucleotide sequence of HPV-57b
      (GenBank 37537), which was molecularly cloned from a benign fungiform papilloma,
      and compared it with other HPV types and HPV-57a, which was cloned from an
      inverted papilloma of the maxillary sinus by de Villiers et al. (Virology 171,
      248. 1989). Comparative and phylogenetic analysis of amino acid sequences of the
      HPV-57b oncogenes E5, E6, and E7 were performed with HPV-6, 11, 16, and 18.
      Phylogenetic trees using the Jotun-Hein algorithm indicated a closer relationship
      of HPV-57b E5 and E7 with corresponding genes of HPV-18. Signature pattern
      analysis of these two oncogenes was also in agreement with a closer relatedness
      to HPV-16 and 18 oncogenes, which are associated with a high risk for malignant
      progression. Compared with 7861 bp of HPV-57a, HPV-57b had 7868 bp as well as
      differences in the restriction enzyme sites and the open reading frames,
      including at least five additional ones. To investigate the oncogenic potential
      of HPV-57b, NIH 3T3 and REF52 cells were cotransfected with two plasmids: pKP54.
      HPV-57b, which contains the HPV-57b genome, and pMT.neo.1, which confers
      resistance to G418. After selection in culture medium containing G418, 58% of the
      G418r NIH 3T3 colonies and 47% of the G418r REF52 colonies exhibited
      morphological transformation. These results indicate that the transcriptional
      regulatory elements and the oncoproteins of HPV-57b are active in vitro to induce
      cellular transformation, as are other high-risk HPV types.

PMID- 8879134
TI  - Nucleotide sequence of the matrix protein gene of a subgroup B avian pneumovirus.
AB  - The nucleotide sequence of the gene encoding the matrix protein of a subgroup B
      avian pneumovirus has been determined. The gene shows 73.5% homology with that of
      a subgroup A virus, with most differences occurring in the third codon position.
      Comparison with pneumovirus matrix proteins shows that the APV matrix protein
      retains the hydrophobic domain common to the others. The analysis indicates that
      the matrix protein gene can be used to differentiate the two APV subgroups.

PMID- 8879135
TI  - Identification and nucleotide sequence of the thymidine kinase gene of canine
      herpesvirus.
AB  - This paper presents the entire nucleotide sequence of the thymidine Kinase (TK)
      gene of canine herpesvirus (CHV). The gene was located within a 2.1 kbp EcoRV
      fragment by Southern-blot hybridization with a probe derived from the known
      feline herpesvirus type 1 (FHV-1) TK gene. An open reading frame (ORF) of 987
      nucleotides, capable of encoding a TK translation product of 328 amino acids, was
      identified. Alignment of the predicted amino acid sequence of the CHV TK with
      other herpesvirus TKs revealed homologies of 25-47%. The proposed nucleotide
      binding site and thymidine-binding site sequences of known herpesvirus TKs could
      be aligned with similar sequences in CHV TK. Northern-blot analysis revealed 1.3
      kb and 5.0 kb mRNAs as the TK-specific transcripts. It is probable that the 1.3
      kb transcript codes for the CHV TK and that the 5.0 kb transcript codes for the
      CHV TK and the downstream sequence.

PMID- 8879136
TI  - Microheterogeneity of p60 capsid protein and the encoding gene among contemporary
      isolates of rabbit hemorrhagic disease virus.
AB  - The gene encoding the p60 capsid protein from a Spanish isolate of the rabbit
      hemorrhagic disease virus (RHDV) has been cloned and sequenced. Both cDNA and the
      derived protein sequences have been compared with those from several contemporary
      European RHDV isolates. Genetic heterogeneity among co-circulating viruses is
      nearly constant along the p60-encoding gene, around 0.034 substitutions per
      nucleotide, and it does not allow prediction of the preferential regions for long
      term fixation of mutations. However, sequence comparisons with the more distant,
      but phylogenetically closely related calicivirus, the European brown hare
      syndrome virus (EBHSV), reveal a great extent of genetic variability within both
      a segment of p60 gene (nucleotides 900-1300) and the encoded polypeptide,
      suggesting the existence of strong selective pressures acting over this region of
      the capsid protein.

PMID- 8879137
TI  - Enhancement of HSV-DNA infectivity, in Vero and RS cells, by a modified calcium
      phosphate transfection technique.
AB  - Infectivity of herpes simplex virus (HSV) DNA was assessed by employing the
      calcium-phosphate transfection technique described by Chen and Okayama,
      originally applied to increase the efficiency of plasmid transfection by N, N-bis
      (2-hydroxyethyl)-2-aminoethane sulfonic acid (BES). The experimental conditions
      and efficiency of this transfection procedure were evaluated comparing the viral
      progeny titers obtained by the Chen and Okayama transfection method using DNA
      from wild-type strains of HSV-1 and HSV-2, as well as from mutant strains, with
      the viral progeny obtained by the most widely used transfection technique
      introduced by Graham and van der Eb. Furthermore, recombinant virus production
      was evaluated in marker transfer and marker rescue experiments, comparing both
      transfection techniques, using DNA fragments cotransfected with whole viral DNA
      into African green monkey (Vero) or rabbit skin (RS) cells. The viral production
      obtained from HSV-DNA transfected cells was enhanced approximately 1000-fold when
      the Chen and Okayama procedure was applied.

PMID- 8879138
TI  - Mutations in the hemagglutinin and matrix genes of a virulent influenza virus
      variant, A/FM/1/47-MA, control different stages in pathogenesis.
AB  - The mouse adapted strain of influenza A/FM/1/47 virus, FM-MA, has increased
      virulence due to mutations in HA, M1 and at least one other, unmapped, genome
      segment. Genetic reassortants that differ due to the HA or M1 mutations were used
      to define the role of these mutations in pathogenesis. Pathological changes in
      lungs of infected mice were assessed by hematoxylin phloxine saffron (HPS)
      staining, and viral infection was measured by fluorescent antibody staining of
      thin sections and flow cytometry of lung parenchymal cells. HA played a role in
      bronchiolar pathology by increasing necrosis of bronchiolar epithelium,
      peribronchiolar lymphocytes, and airway obstruction. The HA mutation was shown to
      be responsible for a 0.2 unit decreased in the pH optimum of fusion and
      controlled resistance to alpha and beta inhibitors of hemagglutination. Both
      these changes in biology may confer a replicative advantage in bronchioles seen
      in the first day of infection. Thus the HA mutation may have conferred a survival
      advantage in the extracellular lung environment. The M1 mutation resulted in
      improved growth in the lung and cultured cells and was associated with increases
      in recruitment of macrophages, spread of infection into the alveoli of the lung
      and interstitial pneumonia. Sequence analysis indicated that the unmapped
      mutation in the control of FM-MA virulence is either the K482-->R substitution in
      the PB2 protein or the D538-->G substitution in the PB1 protein. One or other of
      these mutations results in a growth advantage in infected lung but not in
      cultured cells as well as a further increased recruitment and infection of
      macrophages in the lung. Infection with virulent strains of influenza that
      induced increases in macrophage recruitment caused hypothermia in the mouse.

PMID- 8879139
TI  - The production of a truncated form of baculovirus expressed EHV-1 glycoprotein C
      and its role in protection of C3H (H-2Kk) mice against virus challenge.
AB  - A truncated form of the equine herpesvirus 1 (EHV-1) glycoprotein C (gC) gene was
      expressed in baculovirus. The gC signal sequence was substituted with the
      honeybee melittin signal sequence and the transmembrane region was replaced with
      a histidine tag. The recombinant virus produced high levels of gC in both the
      cells and supernatants of infected cells. The protein was present by 24 h and
      maximal secretion occurred at 96 h post-infection. The recombinant protein was
      antigenically authentic as shown by its reaction with each of a panel of
      individual monoclonal antibodies specific for the five distinct antigenic sites
      on EHV-1 gC. Recombinant gC was purified from the supernatant of infected cells
      by immuno-affinity chromatography and used to immunize C3H (H-2Kk haplotype)
      mice. This incurred a gC specific antibody response against both the recombinant
      protein and EHV-1 gC. 'Pepscan' analysis showed that the gC specific antibodies
      in serum from these mice reacted with the same epitopes on gC as those recognized
      by antibodies in convalescent equine sera (i.e. antibodies were specific to
      antigenic sites one and five). A third previously unrecognized antibody binding
      site at the carboxyl terminus was also detected (Antibody binding domain I). A T
      cell proliferative response against EHV-1 was detected in splenocyte populations
      taken from vaccinated mice. Further, the recovery of virus from the lungs and
      turbinates following challenge of mice with EHV-1 was significantly reduced.
      These findings indicate that baculovirus expressed gC may contribute
      significantly to a subunit vaccine preparation aimed at protecting horses from
      EHV-1 infection.

PMID- 8879140
TI  - Characterisation of Wongorr virus, an Australian orbivirus.
AB  - Sequence analyses of VP3 gene segments of Wongorr virus isolates from the
      Northern Territory of Australia were compared with the cognate gene segments from
      Picola and Paroo River viruses. Previous serological investigations had
      demonstrated some relationships between these viruses, however VP3 gene sequence
      and phylogenetic analyses placed these viruses within the same serogroup which
      was distinct from other described orbivirus serogroups. A polymerase chain
      reaction (PCR) was developed for the detection of this serogroup and used to
      identify and determine partial sequence data for other isolates of the virus.
      Wongorr virus and the other tick and mosquito-borne orbiviruses (Kemerovo and
      Corriparta), were more closely related than the Culicoides transmitted
      orbiviruses, such as bluetongue (BTV) and African horse sickness virus (AHSV)
      which were shown to be on a separate branch of the orbivirus phylogenetic tree.

PMID- 8879141
TI  - Characterization of a calcium binding domain in the VP1 protein of the avian
      polyomavirus, budgerigar fledgling disease virus.
AB  - Calcium ions appear to play a major role in maintaining the structural integrity
      and assembly of papovavirus virions and are likely involved in the process of
      viral uncoating. Recently it was reported that the purified recombinant VP1
      protein of budgerigar fledgling disease virus (BFDV) was capable of assembling
      into capsid-like particles in the presence of calcium. It is now reported that
      the major capsid protein VP1 of BFDV binds calcium ions in an in vitro calcium
      binding assay. Two deletions were made in the VP1 protein to identify a calcium
      binding domain and to further characterize the role of calcium ions in the capsid
      assembly process. Recombinant VP1 lacking a putative calcium binding domain (Asp
      237-Asp-248) failed to bind radioactive 45Ca2+ yet associated into capsomeres.
      These capsomeres were similar in shape to the wild-type VP1 but were unable to
      assemble into capsid-like particles. Likewise, recombinant VP1 lacking ten
      carboxyl terminal amino acids (Glu-334-Arg-343) also formed capsomeres that were
      unable to assemble into capsid-like particles. In contrast to the VP1 protein
      with the internal deletion, the protein with the truncated carboxyl terminus
      bound 45Ca2+ in the in vitro assay. These results have identified a calcium
      binding domain (Asp-237-Asp-248) for the BFDV VP1 protein and a crucial role for
      the VP1 carboxyl terminal amino acids (Glu-334-Arg-343) in capsid assembly.

PMID- 8879142
TI  - The UL3 open reading frame of herpes simplex virus type 1 codes for a
      phosphoprotein.
AB  - Based on sequence analysis, the protein encoded by the UL3 open reading frame
      (ORF) of herpes simplex virus type 1 (HSV-1) was predicted to contain an N
      glycosylation site and to be a glycoprotein. To determine if this prediction was
      correct, we cloned and expressed the DNA encoding the complete sequence of the
      UL3 ORF in a baculovirus expression system. Western blotting was done using
      polyclonal antibody raised against synthetic UL3 peptides. Two major baculovirus
      UL3 expressed protein bands with apparent molecular weights of 30 kDa and 31 kDa,
      and two minor protein bands with apparent molecular weights of 29 kDa and 33 kDa
      were detected. None of the expressed UL3 protein species were susceptible to
      tunicamycin treatment, suggesting that they were not N-linked glycosylated. Cell
      fractionation studies indicated that the UL3 protein was localized in the
      cytoplasmic and nuclear portion of the cells, rather than the cell membrane,
      again suggesting a lack of glycosylation. In contrast, the baculovirus expressed
      UL3 protein was phosphorylated as judged by 32Pi-labeling. Immunoprecipitation
      followed by SDS-PAGE demonstrated a single 32Pi-labeled UL3 related band with an
      apparent molecular weight of 33 kDa, indicating that the UL3 protein was a
      phosphoprotein. Antibodies produced in mice vaccinated with baculovirus-UL3
      protein reacted with two UL3 related HSV-1 bands on Western blots. These protein
      bands had apparent molecular weights of 27 and 33 kDa and presumably represent
      the unphosphorylated and phosphorylated forms of UL3.

PMID- 8879143
TI  - In vitro metabolism of a rifamycin derivative by animal and human liver
      microsomes, whole blood and expressed human CYP3A isoform.
AB  - 1. In vitro metabolism of a rifamycin derivative, benzoxazinorifamycin KRM-1648,
      was studied using mouse, rat, guinea pig, dog, monkey and human liver microsomes.
      30-Hydroxy-KRM-1648 (M2) was produced in mouse, dog, monkey and human microsomes.
      25-Deacetyl-KRM-1648 (M1) was produced in dog and human microsomes, but not in
      mouse or monkey microsomes. Neither M1 nor M2 was detected in rat or guinea pig
      microsomes. 2. In dog and human liver microsomes the formation of M2 was
      dependent on NADPH, but the formation of M1 was not. 3. In vitro metabolism of
      the parent compound was studied in whole blood in some species. Only M1 was
      detected in mouse and rat blood, and not in dog and human blood. 4. These
      findings demonstrated that the metabolite pattern in dog resembled that in man,
      and suggested that the 30-hydroxylation of KRM-1648 was mediated by cytochrome
      P450, but that the 25-deacetylation was not. 5. Among the ten recombinant human
      P450 isoforms used, only the cell lysates including CYP3A3 and CYP3A4 catalysed
      the M2 formation from KRM-1648.

PMID- 8879144
TI  - Use of fresh and cryopreserved hepatocytes to study the metabolism of pesticides
      in food-producing animals and rats.
AB  - 1. The possibility of using hepatocytes from food-producing animals in order to
      determine the metabolic routes of pesticides has been studied using a strobilurin
      fungicide (BAS 490 F). Hepatocytes suspensions were prepared from goat, pig, hen,
      and rat and the major metabolites were compared with those obtained in vivo. 2.
      The hepatocytes gave metabolite patterns matching qualitatively with in vivo
      results, but no good quantitative correlation was found. 3. A freezing and
      thawing method was developed using liquid nitrogen and a programmable freezer,
      which allows acceptable recoveries of functional cells as assessed by glutathione
      and cytochrome P450 contents, and phase I and II enzymatic activities (including
      7-ethoxycoumarin-O-deethylase, ethoxyresorufin-O-deethylase, glutathione-S
      transferase, and UDP-glucuronosyl transferase), with 60-70% viability. 4. The
      cells were damaged through freezing as indicated by the efflux of glutathione (40
      60% of the intracellular content), but remained able to metabolize BAS 490 F,
      partially like fresh cells. A good qualitative but no quantitative matching of
      the metabolite patterns before and after cryopreservation was found, indicating
      that the metabolic activities are affected to variable extents during the
      freezing process. 5. The use of fresh and cryopreserved cells as models for
      metabolism and species comparison, and as a versatile tool to synthesize
      metabolites, is discussed.

PMID- 8879145
TI  - Uptake, disposition, and persistence of nonylphenol from water in rainbow trout
      (Oncorhynchus mykiss).
AB  - 1. Nonylphenol is an environmental estrogenic compound. Little is known about its
      interaction with aquatic species since most of the work on oestrogenic
      alkylphenols has been done in vitro using cells in culture. 2. Rainbow trout
      (Oncorhynchus mykiss) were exposed to 14C-nonylphenol at 18 and 36 ppb in water
      to study its distribution, persistence, and bioaccumulation. 3. Nonylphenol, or
      its metabolites, were distributed through the body of rainbow trout including the
      edible tissues of dorsal muscle and fat. 4. Nonylphenol was rapidly taken up into
      most tissues and had an apparent half-life of 19-20 +/- 4 SE hours in the muscle
      and fat. 5. The apparent bioaccumulation factor in viscera and carcass ranged
      from 40 in carcass to 100 in viscera. 6. Three glucuronide metabolites were
      separated by thin-layer chromatography following treatment of bile with beta
      glucuronidase.

PMID- 8879146
TI  - Nefiracetam hydroxylation by rat liver microsomes and expressed human cytochrome
      P450s.
AB  - 1. The metabolism of nefiracetam, a novel cognition-enhancer, by rat liver
      microsomes has been studied. 2. Formation of 5-hydroxy (5-OH-NEF) and
      hydroxymethyl (HM-NEF) derivatives was the principal pathway of NEF oxidation in
      male rats, and followed Michaelis-Menten kinetics with Km values of 2.9 and 3.3
      mM, and Vmax values of 7.8 and 4.5 nmol/min/mg protein, respectively. 3. Enzymes
      catalysing the formation of these two major metabolites were examined. 5-OH-NEF
      formation was inhibited by antibody to rat CYP3A2 by 60%, and antibodies to
      CYP2B1, CYP2C11 and CYP2E1 also showed 15-25% inhibition of the formation of 5-OH
      NEF. The formation of HM-NEF was inhibited by antibodies to CYP2C11 and CYP2B1 by
      80% and 35%, respectively. These findings indicate that CYP3A plays a major role
      in the formation of 5-OH-NEF, and CYP2B, CYP2C11 and CYP2E1 are also involved to
      some extent in the 5-hydroxylation, and that CYP2C11 is mainly responsible for HM
      NEF formation, and CYP2B is also involved in that catalysis in male rats. The
      results from the studies of the effects of various chemical inducers, of
      selective substrates or inhibitors of P450s on the formation of these metabolites
      also supported these latter findings. 4. NEF metabolism in microsomes prepared
      from B-lymphoblastoid cells expressing human cytochrome P450s showed that 5-OH
      NEF formation by CYP3A4 is the principal metabolic pathway in humans.

PMID- 8879147
TI  - Modulation of rat hepatic CYP3A by nonylphenol.
AB  - 1. In in vitro assays, nonylphenol (NP) inhibited microsomal 5 alpha-reductase
      and steroid hydroxylase activities from the liver of dexamethasone-treated rats.
      The inhibition was specific in that 6 beta-hydroxylase was affected the most
      followed by 16 alpha-hydroxylase. The activity of 17 alpha-hydroxylase remained
      unchanged. 2. Enzyme kinetic analyses (Lineweaver Burke plots) using different NP
      concentrations with graded increases in the concentrations of the substrate,
      progesterone, showed that the inhibition was of a mixed competitive and non
      competitive type. 3. In in vivo studies, treatment of rats with NP resulted in a
      dose dependent increase in the hepatic microsomal progesterone hydroxylase
      activity and CYP3A proteins as measured by Western blot analysis. 4. The mixed
      competitive and non-competitive nature of inhibition by NP on hepatic microsomal
      progesterone hydroxylase activity indirectly suggests that this compound may
      behave as a partial substrate of the CYP3A enzyme. More importantly, nonylphenol
      induces the expression of rat hepatic CYP3A which may then affect its own
      metabolism and that of other steroid substrates.

PMID- 8879148
TI  - Interspecies scaling of tolcapone, a new inhibitor of catechol-O
      methyltransferase (COMT). Use of in vitro data from hepatocytes to predict
      metabolic clearance in animals and humans.
AB  - 1. In the present study, in vivo pharmacokinetic data in animals were combined
      with in vitro metabolic data from animal and human hepatocytes to predict the
      human systemic plasma clearance and the kinetic profile of tolcapone, a compound
      metabolized by phase II reactions. 2. The integration of in vitro metabolic data
      from hepatocytes into allometric scaling gave satisfactory predictions of
      metabolic clearance in humans for tolcapone (74.2 ml/min predicted versus 118
      ml/min observed). 3. Using combined time transformations and in vitro metabolic
      rates, the range of values predicted from the various animal species (90.4 to 242
      ml/min, 0.60 to 2.2 h and 7.3 to 121 for clearance, half-life and volume of
      distribution, respectively) were in good agreement with the observed values in
      humans (118 ml/min, 1.3 h and 8.6 h, respectively). 4. Compared to the
      conventional correction factors (e.g. maximum life span, brain weight), in vitro
      metabolic data provide a more rational basis for extrapolating the metabolic
      clearance in humans.

PMID- 8879149
TI  - Metabolism of diethyl 4-[(4-bromo-2-cyanophenyl)-carbamoyl]benzylphosphonate in
      the rat.
AB  - 1. The metabolism of diethyl 4-[(4-bromo-2
      cyanophenyl)carbamoyl]benzylphosphonate (NO-1886), an antilipidaemic agent, was
      evaluated in the rat. 2. 14C-NO-1886 was dosed orally to rats (3 mg/kg) and
      within 24 h after dosing, 27.9 +/- 2.1 and 63.5 +/- 4.2% of the administered
      radioactivity was recovered from urine and faeces respectively. 3. The metabolite
      M-2 was isolated from the urine and faeces, and two other metabolites, M-3 and M
      5, were isolated from the urine. Two of them were identified as ethyl 4-[(4-bromo
      2-cyanophenyl)carbamoyl]benzylphosphonate (M-2) and 4-[(diethoxy
      phosphoryl)methyl)]benzoic acid (M-3), and the other one was considered to be 2
      amino-5-bromo-3-cyanobenzene sulphate (M-5) by ms and nmr spectrometry. 4. The
      major metabolic pathway of NO-1886 was found to be mono-hydrolysis of the diethyl
      phosphonate. It was also considered that M-5 may have been formed in vivo via 2
      amino-5-bromo-benzonitrile (M-1) and 2-amino-5-bromo-3-hydroxybenzonitrile (M-4).

PMID- 8879150
TI  - The disposition of 14C-levamisole in the lactating cow.
AB  - 1. 14C-Levamisole 1(-)-2,3,5,6-tetrahydro-6-phenyl[U-14C]imidazo[2,1-b]-thiazole
      was administered orally and subcutaneously to lactating cows (8 mg/kg body
      weight). Urine, faeces, milk and blood samples were collected from 0-48 h after
      dosing and tissues were collected 48 h after dosing. 2. 14C-Labelled residues
      (ppm 14C-levamisole equivalents) in blood were highest at 3 h (2.2 ppm, oral
      dose) or 6 h (2.1 ppm, subcutaneous dose) and then declined to less than 0.5 ppm
      48 h after dosing. 3. 14C-Labelled residues in milk were highest in samples
      collected from 0-12 h after dosing (1.55 ppm and 1.86 ppm of levamisole
      equivalents from oral and subcutaneously dosed animals, respectively) and
      declined to 0.06 ppm in milk collected from 36-48 h after dosing. Milk collected
      from 0-48 h after dosing accounted for 0.2% (oral dose) and 0.6% (subcutaneous
      dose) of the total 14C-activity administered as 14C-levamisole. The parent
      compound, 14C-levamisole, accounted for 12% or less (declined with time after
      dosing) of the total 14C-activity in the milk. Three 14C-labelled metabolites
      (formed by oxidation of imidazoline ring and/or opening of thiazolidine ring) in
      the milk were isolated and identified. 4. Urinary excretion accounted for 83% and
      84% and faecal excretion accounted for 11% and 9% of the total 14C-activity given
      orally and subcutaneously, respectively, as 14C-levamisole. No 14C-levamisole was
      detected in the urine; the major urinary metabolite (formed by opening of
      thiazolidine ring) was isolated and identified. 5. The 14C-activity remaining in
      the animals 48 h after dosing was widely distributed in body tissues; however,
      the concentration in the liver was substantially higher than in all other tissues
      examined. Less than 5% of the 14C-activity in the liver was present as 14C
      levamisole.

PMID- 8879151
TI  - Captopril methylation in human liver and kidney: interindividual variability.
AB  - 1. The methylation of captopril was studied in the microsomal fraction obtained
      from 87 specimens of human liver and 70 specimens of human renal cortex. 2. The
      rate captopril methylation ranged over one order of magnitude in the liver and
      kidney. In the human liver, the mean (+/- SD) rate of captopril methylation
      (pmol/min/mg) was significantly (p < 0.001) greater in women (199 +/- 97) than in
      men (126 +/- 88), whereas in the kidney no sex-difference was observed, and the
      mean (+/- SD) of all cases was 47 +/- 23 pmol/min/mg. 3. In the kidney, the
      statistical analysis revealed the presence of two subgroups in the rate of
      captopril methylation and their mean (+/- SD) estimates were 42.5 +/- 13.9 and
      90.3 +/- 12.0 pmol/min/mg (p < 0.05). Of the population, 84% fell in the former
      and the remaining 16% in the latter subgroup. 4. Captopril is mainly eliminated
      by metabolism and its bioavailability is 65%. Methylation is one of the metabolic
      routes of captopril and its variability may contribute, to some extent, to
      modulate the intracellular concentration of this drug.

PMID- 8879152
TI  - Applications of the environmental scanning electron microscope to the analysis of
      pharmaceutical formulations.
AB  - Electron microscopy has been used for several years as a routine tool for the
      study of pharmaceutical formulations. However, it is usually desirable to obtain
      information on these systems in the wet state, and there are concerns regarding
      the interpretation of information provided by conventional electron microscopy
      where samples are subjected to preparation techniques which may include freezing,
      drying, fracturing, and coating. The environmental scanning electron microscope
      (ESEM) has been used to analyse a number of pharmaceutical samples in their
      natural state. Results obtained from these samples, including biodegradable
      matrices, microparticulate systems (both degradable and non-biodegradable), and
      bioadhesive matrices, will be discussed and the merits and limitations of the
      ESEM will be highlighted.

PMID- 8879153
TI  - Glycerol production in a triose phosphate isomerase deficient mutant of
      Saccharomyces cerevisiae.
AB  - Interesting challenges from metabolically engineered Saccharomyces cerevisiae
      cells arise from the opportunity to obtain yeast strains useful for the
      production of chemicals. In this paper, we show that engineered yeast cells
      deficient in the triose phosphate isomerase activity are able to produce glycerol
      without the use of steering agents. High yields of conversion of glucose into
      glycerol (80-90% of the theoretical yield) and productivity (1.5 g L-1 h-1) have
      been obtained by a bioconversion process carried out in a poor and clean medium.
      We obtained indications that the growth phase at which the biomass was collected
      affect the process. The best results were obtained using cells collected at the
      end of exponential phase of growth. In perspective, the strategies and the
      information about the physiology of the cells described here could be useful for
      the developing of new biotechnological processes for glycerol production,
      outflanking the problems related to the use of high level of steering agents.

PMID- 8879154
TI  - Growth kinetics of Escherichia coli and expression of a recombinant protein and
      its isoforms under heat shock conditions.
AB  - Preinduction culture conditions were found to have significant impact on the
      expression and post-translational modification of a recombinant human protein in
      Escherichia coli under heat shock conditions (30 to 42 degrees C shift). Higher
      preinduction growth rates (micrograms) favored better cell viability, greater
      cell mass yields, and increased cloned gene expression during induction.
      Formation of recombinant protein isoforms (those containing N epsilon-modified
      lysine residues) exhibited an increasing trend with increasing micrograms. The
      different extents of post-translational modifications were suspected to be linked
      to the different concentrations of certain heat shock protein chaperones
      resulting from different micrograms. In view of the extensive involvement of E.
      coli heat shock proteins in cellular activities-including the synthesis,
      processing, modification, and degradation of proteins-at elevated temperatures,
      it is believed that micrograms dictated the cellular resources available for
      synthesizing the heat shock proteins required for cell survival, which in turn
      determined the ability of the cells to respond to the heat shock. With a higher
      micrograms both the synthesis of host proteins (as indicated by cell growth and
      survival) and the cloned gene expression were enhanced. The results demonstrate
      that there exists an intermediate micrograms for optimum production of the
      unmodified foreign protein in a heat shock environment. More importantly, they
      also illustrate the feasibility of improving the recombinant protein homogeneity
      in fermentation, thereby facilitating downstream processing.

PMID- 8879155
TI  - A semicontinuous prokaryotic coupled transcription/translation system using a
      dialysis membrane.
AB  - This report describes a novel and simple cell-free protein synthesis system. In
      this paper, we prove that the short duration of protein synthesis in a
      conventional cell-free protein synthesis system of batch configuration can be
      attributed both to depletion of energy sources and deactivation of S30 extract by
      small-molecule byproducts produced during the protein synthesis. The reaction
      period of cell-free protein synthesis system could be extended through an
      operation of a continuous-flow cell-free protein synthesis system, which was
      originally developed by Spirin. However, inspite of the greatly extended reaction
      period, the final amount of cell-free produced protein was not significantly
      larger than that can be obtained from a batch system due to the reduced rate of
      protein synthesis. It was supposed that the reduced rate of protein synthesis in
      the continuous-flow system was attributed to leakage of translational components
      through the ultrafiltration membrane during the operation of the continuous-flow
      system. To solve such a problem of the continuous-flow system, we have developed
      and operated a novel reactor for cell-free protein synthesis. By use of this
      system, protein synthesis occurred for at least 14 h, yielding 1.2 mg/mL CAT
      protein. The present system is superior to the continuous-flow system as well as
      the conventional batch system in that it enables extremely high productivity
      without using any complex and hard-to-handle apparatus. As far as we know, the
      yield of cell-free protein synthesis given above is the best of the results
      reported to date.

PMID- 8879156
TI  - Adhesion mediated by bonds in series.
AB  - Cell adhesion in physiological situations and biotechnological applications is
      often mediated through serial protein/protein linkages. The adhesion strength of
      cell/substrate contacts through receptor/ligand bonds in series is explored with
      a simple mathematical model and quantified with an experimental adhesion assay. A
      deterministic, mass-action model is developed to describe the attachment and
      detachment of cell/substrate contacts through single and serial bonds. The
      experimental system is comprised of protein-coated beads, soluble antibody
      linkers, and an antibody-coated glass surface. Using the Radial-Flow Detachment
      Assay, the adhesion strengths of bead/substrate contacts through single and
      serial linkages are measured. Taken together, this work shows that the specific
      adhesion strength of the cell/substrate contacts comprised of two receptor/ligand
      bonds in series is less than the specific adhesion strength of the cell/substrate
      contacts comprised of either of the bonds separately. In addition, the force to
      rupture contacts comprised of bonds in series varies with the concentration of
      the solution linker. The model predicts that the locus of linkage fracture
      location has only a mild dependence on the ratio of relative bond affinities.

PMID- 8879157
TI  - Photoimmobilization of insulin onto polystyrene dishes for protein-free cell
      culture.
AB  - Photoreactive insulin was synthesized by coupling with azidobenzoic acid. The
      insulin derivative was immobilized onto the wells of polystyrene culture plates
      by photoir-radiation. The photoimmobilized insulin enhanced the growth of
      anchorage-dependent cells such as Chinese hamster ovary CHO-K1 and mouse
      fibroblast STO cells by more than native or azidophenyl-derivatized insulin. A
      small amount of photoimmobilized insulin (1-10% of the amount of the native or
      derivatized insulin) enhanced the growth of CHO-K1 and STO cells. In addition,
      the maximal mitogenic effect of the immobilized insulin was greater than that of
      native or derivatized insulin. Photoimmobilization could be a universal means of
      immobilizing growth factors onto the surface of materials devoid of chemical
      functional groups scaffolding growth factors and providing a new protein-free
      cell culture system or tissue engineering materials.

PMID- 8879158
TI  - Mediator-free amperometric determination of toxic substances based on their
      inhibition of immobilized horseradish peroxidase.
AB  - We have demonstrated the feasibility of quantitatively detecting selected toxic
      materials through their inhibitory effect on an enzyme electrode that utilizes
      colloidal gold-immobilized horseradish peroxidase and does not require a
      mediator. Quantitative detection of azide, cyanide, thiourea, sulfide, and
      dichromate is demonstrated. The sensitivity and inhibition kinetics for this
      immobilized enzyme electrode are found to be different from those observed
      previously for homogeneous horseradish peroxidase. Possible reasons for this
      difference are discussed. Due to the availability of a large number of enzymes
      and their toxic inhibitors, this work based on immobilized enzyme inhibition
      coupled to an electrode surface significantly broadens the possible applications
      of biosensors and offers alternative methods for toxic substance determination.

PMID- 8879159
TI  - Effects of growth rate on the production of Pseudomonas fluorescens lipase during
      the fed-batch cultivation of Escherichia coli.
AB  - Recombinant Escherichia coli was grown to produce the thermostable Pseudomonas
      fluorescens lipase by controlling the specific growth rate (mu). At low growth
      rate (mu = 0.07 h-1), a higher cell density (OD600 = 140) was obtained. By
      calculating the cell yield on nitrogen, the medium was optimized to prevent
      inhibition of cell growth by nitrogen unbalance. Acetate accumulated in the broth
      at the same rate as observed in a chemostat under nitrogen-limited fed-batch
      conditions, but not in a glucose-limited fed-batch culture. Postinduction growth
      rate affected lipase production more than preinduction growth rate. After
      induction, more lipase was produced at a low growth rate (mu = 0.1 h-1) than at a
      high growth rate (mu = 0.4 h-1). More lipase was produced at 37 than at 20
      degrees C at a constant growth rate, indicating that temperature affected other
      factors in addition to growth rate.

PMID- 8879160
TI  - Polylinker-encoded peptides can confer toxicity to recombinant proteins produced
      in Escherichia coli.
AB  - Three DNA segments encoding fragments of the p60 capsid protein of rabbit
      haemorrhagic disease virus (RHDV) have been cloned and expressed in Escherichia
      coli. The cDNAs were placed under the control of the T7 promoter in a pET-derived
      expression vector designed to produce C-terminal histidine tail fusions. By using
      different cloning strategies, cell toxicity exhibited by some of the expressed
      products was dramatically affected, coincident with minor modifications in the
      carboxy terminus sequences of the recombinant proteins. In particular, the
      presence of a nonhydrophobic peptide encoded by polylinker sequences promotes
      cell death and a reduced yield after induction of gene expression, whereas a
      histidine tail has no detectable effect. These data point out the critical role
      that needless peptide tails, accidentally introduced into recombinant proteins by
      nonrelevant DNA stretches, can have on protein expression and final yield of a
      production process.

PMID- 8879161
TI  - Modification of biochemical pathways in industrial yeasts.
AB  - Yeasts have many applications in industrial food and beverage production. While
      these uses are often of ancient origin, modern demands for control of the amounts
      of process-derived compounds and for cost-effective processing can make it
      desirable to modify metabolic pathways of production yeasts. While the genetics
      of standard laboratory strains of Saccharomyces cerevisiae are well described,
      industrial strains and species are less characterized, and many of them have a
      complicated genetic constitution. Nevertheless, their biochemical pathways can be
      modified, and the knowledge becoming available on the physiology of genetic
      reference strains of S. cerevisiae is a great help in directing the modifications
      of the industrial yeasts towards practical goals.

PMID- 8879162
TI  - Increased resistance to 14 alpha-demethylase inhibitors (DMIs) in Aspergillus
      niger by coexpression of the Penicillium italicum eburicol 14 alpha-demethylase
      (cyp51) and the A. niger cytochrome P450 reductase (cprA) genes.
AB  - In this paper we describe the effects of over-expression of the Penicillium
      italicum gene encoding eburicol 14 alpha-demethylase (cyp51), in Aspergillus
      niger strains with one or multiple copies of the gene encoding cytochrome P450
      reductase (cprA), on the eburicol 14 alpha-demethylase activity. Eburicol 14
      alpha-demethylase activity was determined by measuring the resistance of
      transformants against some eburicol 14 alpha-demethylase inhibitors (DMIs). DMIs
      are widely used as fungicides in crop protection and human and veterinarian
      health care. DMI resistance in a transformant overexpressing both CPR and CYP51
      was increased 5-30-fold compared to DMI resistance in the wild type strain,
      depending on the test compound used. Resistance in this strain was approximately
      2-5-fold increased compared to DMI resistance in a transformant that was
      overexpressing the cyp51 gene but had only the wild type copy of the cprA gene
      and approximately 3-12-fold increased compared to a strain overexpressing the
      cprA gene (and having only the wild type copy of the cyp51 gene). These results
      show the importance of CPR overexpression for increasing cytochrome P450
      activities in filamentous fungi.

PMID- 8879163
TI  - Fast purification and kinetic studies of the glycerol-3-phosphate dehydrogenase
      from the yeast Saccharomyces cerevisiae.
AB  - The glycerol-3-phosphate dehydrogenase has been purified from Saccharomyces
      cerevisiae 140-fold to electrophoretic homogeneity by a simple procedure
      involving affinity and ion exchange chromatography. The purified enzyme was most
      active at pH 6.8 and 51 degrees C. Its molecular mass was determined to be 45000
      +/- 2000 Da by SDS-polyacrylamide gel electrophoresis. At physiological pH values
      the thermodynamic equilibrium constant was determined to be 3.5 x 10(-3) (M-1).
      Product inhibition as well as competitive inhibition patterns were found which
      clearly indicate that the kinetic mechanism of the glycerol-3-phosphate
      dehydrogenase is random bi-bi with the formation of dead-end complexes. In vivo
      concentrations of selected metabolites and kinetic expression for G3P-DH were
      used to explain regulatory properties of this enzyme under conditions of short
      term glucose effect in Saccharomyces cerevisiae.

PMID- 8879164
TI  - Formation of recombinant proteins in Escherichia coli under control of a nitrogen
      regulated promoter at low and high cell densities.
AB  - The use of a modified Escherichia coli glnAP2 promoter results in the formation
      of both homologous and heterologous, cytoplasmic and periplasmic recombinant
      proteins in a nitrogen concentration dependent manner. As in the E. coli nitrogen
      regulatory system, glnAP2 controlled gene expression is induced when ammonium
      concentration in the growth medium is below 1 mM (nitrogen limitation), otherwise
      only extremely low expression of recombinant genes is observed. Both high cell
      density cultivations (HCDC) and low cell density cultivations (LCDC) gave similar
      results for inducibility and formation of the following recombinant proteins:
      chloramphenicol-acetyltransferase, phosphorylcholine binding mini-antibodies
      (scFv-dhlx of McPC603) and K1-streptokinase. Recombinant proteins were formed in
      quantities of about 2-3% of total cellular protein. At low cell densities,
      slightly higher quantities resulted under partial nitrogen limitations than under
      total nitrogen limitation. In contrast, high cell density cultivations resulted
      in lower product concentrations at partial nitrogen limitation compared with
      total nitrogen limitation. These lowered product concentrations were probably due
      to the very high amounts of K+ or Na+ ions which accumulated during pH
      regulation, thereby disturbing growth. HCDC under partial nitrogen limitation
      decreased proteolysis of recombinant proteins, therefore reduced amounts of
      proteases are considered to be responsible.

PMID- 8879165
TI  - Rapid sampling, cell inactivation and evaluation of low extracellular glucose
      concentrations during fed-batch cultivation.
AB  - A method for rapid extracellular sampling, cell inactivation and handling of a
      large number samples has been developed and evaluated. This method might be used
      during experiments, where concentrations of extracellular components in the range
      of some milligrams per litre has to be evaluated. The analysis should be
      performed by enzymatic or colorimetric analysis and is shown to be suitable for
      measuring low nutrient concentrations present in fed-batch cultivation. The test
      organisms were Escherichia coli and Saccharomyces cerevisiae and the model
      substance was glucose. Using this technique, the sample can be taken in less than
      0.15 s, a time during which negligible glucose is shown to be consumed from the
      sample. The glucose consumption is stopped by a rapid pH decrease using
      perchloric acid in a defined concentration that depended on the organism studied.
      This concentration was chosen in order to avoid cell lysis that could affect the
      glucose concentration by the intracellular release of glucose containing
      compounds and thereby expose them to the acid. It was seen that the sample mixed
      rapidly with the acid and that no hydrolysis of glucose related compounds
      interfered with the analysis. The samples were neutralised and the precipitation
      centrifuged to minimise the effect on the chosen enzymatic analysis. This
      analysis was modified and the accuracy determined in order to analyse
      concentrations in the milligram range. A method to increase the handling of a
      large number of samples was also devised which is based on measurements on
      microtiter plates and allows samples to be evaluated with a high statistical
      accuracy with minimum sample waste in a short time. The ability of the method is
      shown by a study of the metabolic response of a shift in glucose feed, as
      followed by glucose analysis.

PMID- 8879166
TI  - Use of a modified alcohol dehydrogenase, ADH1, promoter in construction of
      diacetyl non-producing brewer's yeast.
AB  - The bacterial gene, encoding alpha-acetolactate decarboxylase (alpha-ALDC), was
      expressed in a bottom-fermenting brewer's yeast under the control of a modified
      Saccharomyces cerevisiae alcohol dehydrogenase (ADH1) promoter which lacks the
      upstream regions from -800 bp to -1500 bp. In pilot scale brewing conditions, the
      level of alpha-ALDC produced was high enough to reduce the concentration of
      diacetyl so that lagering was not required. alpha-ALDC active brewer's yeast
      strains were also shown to be suitable for high gravity brewing.

PMID- 8879167
TI  - High speed centrifugal separator for rapid on-line sample clarification in
      biotechnology.
AB  - Sample clarification is a common operation in biochemical analytical methods for
      removing interfering or unwanted particulates from an analyte sample. Filtration
      provides one option for removal of particulates. However, in many cases the loss
      of soluble protein due to filter adsorption is unacceptable and an alternative
      must be sought. In this paper a microcentrifuge designed to automatically sample,
      spin, deliver supernatant to an analyser and wash out solids from the bowl is
      described. The performance of the system is assessed in terms of its
      clarification efficiency and the time required to achieve satisfactory
      clarification. Additionally, the effects of different protein precipitating
      agents on yeast homogenate samples separated using the microcentrifuge are
      studied where the system is used to deliver supernatant to a flow injection
      analyser. The paper demonstrates that the microcentrifuge may be used to separate
      rapidly such samples on a time scale between 10-60 s depending upon the type and
      size of sample and be successfully used as a component of an at-line monitoring
      system.

PMID- 8879168
TI  - Modelling hybridoma cell growth and metabolism--a comparison of selected models
      and data.
AB  - Unstructured models for cell growth (cell specific growth and death rate) and
      metabolism (cell specific substrate uptake and metabolite production rates) of
      hybridoma cell lines were compared with special respect to significance,
      analytical error and range of validity. The diversity of the unstructured models
      cited reveals their mostly descriptive character compared to structured models.
      Bearing in mind this limited knowledge, empirical models can still serve as a
      valuable tool for process design. For understanding of the cell metabolism itself
      they might have been overemphasized in the past. For proper model design, care
      has to be taken to cover the whole range of process conditions. In particular if
      a process is to be run at very low substrate and high metabolite concentrations,
      chemostat cultures which have mostly been used for the model formulations, are
      not sufficient and have to be completed by, for example, fed-batch cultures.

PMID- 8879169
TI  - Quantitative analysis of transient gene expression in mammalian cells using the
      green fluorescent protein.
AB  - The green fluorescent protein (Gfp) has been used as a reporter, along with flow
      cytometric analysis, to follow the dynamics of gene expression in transiently
      transfected mammalian cells. Gene transfer conditions for lipofection were
      optimized. The highest fraction of transfectants were obtained when lipid-DNA
      complexes were formed with 6 microliters lipid and 1 microgram DNA for chinese
      hamster ovary (CHO) cells and with 9 microliters lipid and 2 micrograms DNA for
      NIH/3T3 cells. Chinese hamster ovary cells were monitored for Gfp expression and
      growth for 6 days following transfection. An initial decrease in viability for 36
      h was observed after which cell growth followed exponential kinetics with
      increasing viability. Intracellular accumulation of recombinant protein peaked at
      24 h post-transfection and then decreased with first order kinetics at a rate
      comparable to the specific growth rate. It appears that dilution by growth
      accounts for the decrease of Gfp in the biomass. Immunofluorescent staining of
      Gfp and subsequent flow cytometric analysis of transfected cells revealed a
      linear correlation between the green fluorescence and immunofluorescence. This
      indicates that green fluorescence is a quantitative measure of intracellular Gfp
      in single cells in spite of the dynamics of post-translational modifications
      involved in the conversion of expressed protein into its fluorescent form. A
      structured model has been formulated to describe the observed kinetics of gene
      expression and fluorophore formation. The model accurately predicts experimental
      trends and suggests that the fraction of non-fluorescent Gfp is significant only
      during the initial period of gene expression.

PMID- 8879170
TI  - The direct cloning of the immunoglobulin VH genes from primary cultured B cells
      specific for a short peptide.
AB  - A new and simple method was devised to obtain immunoglobulin VH genes directly
      from primary cultured B cells specific for a short peptide. Peptide-specific B
      cells were separated from splenocytes of peptide-immunized BALB/c mice with
      antigen-coated magnetic beads, and were cloned by a limitedly diluted culture in
      the presence of lipopolysaccharide, recombinant interleukin (rIL) -2, rIL-4 and
      rIL-5, and 3T3 fibroblasts as filler cells for 7 days. Seventeen clones were
      obtained from 3 x 10(3) fractionated cells by screening the positive wells
      containing anti-peptide antibody-secreting cells by an enzyme-linked
      immunosorbent assay (ELISA). The VH cDNAs of these clones were amplified by a set
      of primers; a primer complementary to the mu-chain constant region gene and the
      other with high complementarity to most of the VH genes. This is the first report
      of success in obtaining unknown VH genes directly from primary B cell clones,
      after their antigen-specificity has been confirmed by ELISA. This new method will
      provide a powerful tool for designing specific recombinant antibodies.

PMID- 8879171
TI  - Cloning and characterization of the gene for the thermostable xylanase XynA from
      Thermomyces lanuginosus.
AB  - A thermostable xylanase from the filamentous fungus Thermomyces lanuginosus (DSM
      5826) was purified. This enzyme has an apparent molecular weight of 24-26 kDa as
      determined by SDS polyacrylamide gel electrophoresis. cDNA and genomic DNA
      fragments coding for this enzyme were cloned and sequenced. The cDNA contains an
      open reading frame encoding a polypeptide of 225 amino acids and was functionally
      expressed in E. coli as a LacZ fusion protein. Comparison of the cDNA sequence
      with the genomic DNA sequence showed that the xylanase was encoded by two exons
      interrupted by an intron of 106 bp. Comparison of the deduced amino acid sequence
      to other published xylanases revealed high homology to xylanases of the family G
      glycanases.

PMID- 8879172
TI  - Rapid determination of plasmid copy number.
AB  - Plasmid copy number, the number of expression vectors per host cell, is a key
      variable in recombinant microbial cultivation. Therefore, it would be very
      helpful, if the plasmid copy number could be determined during the operating
      process period. A rapid quantification of this important process variable would
      even open the possibility of its use in process control. However current assays
      like gel electrophoresis, CsCl-gradient centrifugation, HPLC and other methods
      are time consuming and difficult to quantify. Indirect methods, like the
      correlation of copy number with, e.g. the activity of an enzyme, coded on the
      plasmid, are prone to errors due to the production kinetics, turnover rate and
      protein denaturation. Here, a method is presented, which enables the plasmid copy
      number to be determined in less than 30 min. This novel procedure based on
      plasmid isolation by means of a commercial DNA-isolation kit and quantification
      by capillary electrophoresis, should allow the copy number to be used in process
      control.

PMID- 8879173
TI  - Expression and purification of a recombinant metal-binding T4 lysozyme fusion
      protein.
AB  - Periplasmic expression of recombinant proteins presents many potential benefits
      that may aid recovery of the protein product. Muramidases are the preferred
      agents in effecting selective release of recombinant proteins from the periplasm
      of E. coli and other Gram negative bacteria. Unfortunately cost restricts the use
      of pure lytic enzymes at large-scale and their removal as process contaminants
      adds to later purification demands. We constructed a reusable version of
      bacteriophage T4 lysozyme, by fusing a His-Gln-(His)3 peptide sequence to the C
      terminus of a cysteine-free pseudo wild type bacteriophage T4 lysozyme. The
      peptide tail allowed rapid and high-level recovery on IDA Sepharose columns
      charged with Zn2+, Ni2+ and Cu2+ ions. The binding to metal-charged supports was
      specifically mediated by the histidine-rich tail as no binding was observed for
      the original cysteine-free pseudo wild type lysozyme. The strength of retention
      of polyhistidine recombinant T4 lysozyme on charged supports followed the
      expected Cu > Ni > Zn pattern, but there were few differences in the levels of
      purity and recovery of the modified enzyme, from columns charged with the
      different metal ions.

PMID- 8879174
TI  - Increased production of recombinant pyrroloquinoline quinone (PQQ) glucose
      dehydrogenase by metabolically engineered Escherichia coli strain capable of PQQ
      biosynthesis.
AB  - We have previously shown that the production of recombinant Escherichia coli
      PQQGDH was greatly improved by using a medium supplemented with the cofactor PQQ,
      which is not synthesized in E. coli. We show here that the increase in the
      accumulated PQQGDH is due to the increased stability of the holo-enzyme over apo
      enzyme, using recombinant Acinetobacter calcoaceticus PQQGDH. In order to achieve
      cost-effective PQQGDH production, we incorporated the genes for PQQ biosynthetic
      pathway from Klebsiella pneumoniae into E. coli, which as a result allowed E.
      coli to produce PQQ. Using this metabolically engineered E. coli strain as a
      host, a 10-fold increase in the production of recombinant A. calcoaceticus PQQGDH
      was achieved, compared to the condition without PQQ and MgCl2.

PMID- 8879175
TI  - Different PrlA proteins increase the efficiency of periplasmic production of
      human interleukin-6 in Escherichia coli.
AB  - The export efficiency of a fusion of the Escherichia coli preOmpA signal peptide
      to human interleukin-6 can be significantly raised by coexpressing three
      different prlA alleles of sec Y along with wild type secE. The effect seems prlA
      specific, as prlG1 (a prl allele of secE) does not affect the export of preOmpA
      hIL-6. Coexpression of secD and secF also stimulates the export of the fusion
      protein.

PMID- 8879176
TI  - Keratinocyte growth factor reduces lung damage due to acid instillation in rats.
AB  - Acid aspiration is a serious complication of anesthesia and other forms of
      unconsciousness that can result in the adult respiratory distress syndrome
      (ARDS), which continues to have a very high mortality despite our current
      therapeutic interventions. This type of injury damages the alveolar epithelium,
      principally alveolar type I cells, and requires proliferation of alveolar type II
      cells to restore gas exchange units. Since keratinocyte growth factor (KGF) has
      been shown to be a potent mitogen for alveolar type II cells, we evaluated
      whether intrabronchial administration of KGF would minimize lung injury due to
      the unilateral instillation of 0.1 N hydrochloric acid (HCl). Rats were
      pretreated or post-treated by intrabronchial instillation of KGF (5 mg/kg) into
      the left lung before HCl instillation. All rats receiving KGF at 48 or 72 h
      before HCl instillation survived for the 7-day observation period, whereas the
      mortality rate for those receiving HCl alone or saline followed by HCl was 31%
      and 33%, respectively. Pretreatment with KGF at 72 h but not at 24 or 48 h
      considerably ameliorated morphologic damage produced by HCl. Inflammatory cells
      in bronchoalveolar lavage were markedly decreased 3 and 7 days after HCl
      instillation by the 72-h KGF pretreatment. Pretreatment with KGF at 72 h also
      attenuated the reduction of total lung capacity, decreased the alpha 1(I)
      procollagen mRNA levels, and diminished hydroxyproline accumulation due to HCl
      instillation. Saline pretreatment at 72 h had no significant effect on the HCl
      injury and subsequent physiologic abnormalities. Our attempts to improve outcome
      with post-treatment instillation of KGF were unsuccessful. We conclude that KGF
      pretreatment reduces lung injury due to acid instillation and can prevent
      subsequent pulmonary fibrosis.

PMID- 8879177
TI  - Eosinophil infiltration in nonallergic chronic hyperplastic sinusitis with nasal
      polyposis (CHS/NP) is associated with endothelial VCAM-1 upregulation and
      expression of TNF-alpha.
AB  - We studied potential mechanisms of eosinophil accumulation in nonallergic chronic
      hyperplastic sinusitis with nasal polyposis (CHS/NP). We measured expression of
      endothelial vascular cell adhesion molecule-1 (VCAM-1), which mediates selective
      eosinophil transendothelial migration, the cytokines interleukin (IL)-1 beta, TNF
      alpha and IL-13 which upregulate VCAM-1 expression, and the chemokine RANTES
      which mediates lymphocyte, monocyte, and eosinophil chemotaxis in chronic
      hyperplastic sinusitis with nasal polyposis (CHS/NP) nasal polyps (nonallergic
      versus allergic) and middle turbinate biopsies from normal controls. By
      immunohistochemical staining, the density of EG2+ eosinophils was increased in
      both the nonallergic and allergic CHS/NP subgroups compared to normal controls.
      VCAM-1 expression was significantly increased in CHS/NP subjects compared to
      normal controls (P = 0.0005), with the highest intensity seen in nonallergic
      CHS/NP. By in situ hybridization, the densities of IL-1 beta, TNF-alpha, IL-13,
      and RANTES mRNA+ cells were all increased in nonallergic CHS/NP compared to
      normal controls (P = 0.009, 0.0005, 0.0005, and 0.001, respectively). In
      comparison to allergic CHS/NP, nonallergic CHS/NP had a significantly higher
      tissue density of TNF-alpha (P = 0.04) and a lower density of IL-13 (P = 0.005)
      mRNA+ cells. In general, VCAM-1 expression correlated strongly in CHS/NP with the
      density of TNF-alpha (R = .91, P = 0.0005) but not the density of IL-1 beta, IL
      13, or RANTES mRNA+ cells. We conclude that upregulation of VCAM-1 and
      elaboration of RANTES may contribute to the marked accumulation of eosinophils in
      nonallergic CHS/NP. TNF-alpha may play a critical role in VCAM-1 upregulation in
      this nonallergic eosinophilic disorder.

PMID- 8879178
TI  - Quantitation of the alveolar distribution of surfactant mixtures in normal and
      injured lungs.
AB  - The uptake and distribution of two surfactant mixtures, Exosurf and Infasurf,
      instilled into the lungs of normal and hyperoxia-exposed (100% O2, 60 h) rabbits,
      were quantified at the alveolar level using flow cytometry and fluorescence
      microscopy. The surfactants were labeled with the fluorescent phospholipid analog
      NBD-C12-PC (1-palmitoyl-2-[12-[(7-nitro-2-1, 3-benzoxadiazol-4
      yl)amino]dodecanoyl]-sn-glycero-3-phosphocholine ) in 100:1 molar ratio. Rabbits
      were killed 2 h after the instillation of either surfactant (80 mg phospholipid
      [PL]/kg), and alveolar macrophages (AM) and alveolar type II (ATII) cells were
      isolated and examined for the presence of NBD fluorescence. The fractions of
      cells, with NBD fluorescence values higher than autofluorescence, isolated from
      the lungs of air-breathing rabbits instilled with either Infasurf or Exosurf,
      were 84% and 63% for AM, and 55% and 45% for ATII cells. Exposure of rabbits to
      hyperoxia decreased the fraction of NBD-positive AM following Infasurf
      instillation, and the mean increase in NBD-associated fluorescence in ATII cells
      following Exosurf instillation. Our results suggest that sublethal hyperoxia
      decreases the short-term uptake but not the distribution of intratracheally
      instilled Exosurf.

PMID- 8879179
TI  - Human lung fibroblasts inhibit tumor necrosis factor-alpha production by LPS
      activated monocytes.
AB  - Mononuclear phagocytes are important regulators of normal immune, inflammatory,
      and fibrotic responses. These functions are mediated through the production of
      several cytokines, including tumor necrosis factor-alpha (TNF-alpha), which
      regulate the activity of inflammatory and tissue structural cells such as
      fibroblasts. It is increasingly evident that fibroblasts are also capable of
      releasing a number of cytokines and soluble factors that can, in turn, interact
      with monocytes and thereby modulate the inflammatory process. In this study we
      provide evidence that human lung fibroblasts, through the release of soluble
      factors such as prostaglandin E2 (PGE2), inhibit both TNF messenger ribonucleic
      acid (mRNA) accumulation and TNF-alpha protein release by lipopolysaccharide
      (LPS)-activated human peripheral blood monocytes (PBM). Reverse transcriptase
      polymerase chain reaction (RT-PCR) results showed that fibroblast-conditioned
      medium (FCM) caused a 50% reduction of the TNF-alpha transcript accumulation in
      LPS-stimulated monocytes. Furthermore, FCM induced a significant decrease in the
      release of TNF-alpha by LPS-activated PBM. This effect was dependent on the
      concentration of the FCM and the number of fibroblasts producing it. The maximal
      effect was seen with monocytes cultured in 100% FCM produced by 2 x 10(6)
      fibroblasts. This indicated that one or possibly more soluble factors released by
      fibroblasts were responsible for the effect. Considering that exogenous PGE2 can
      inhibit TNF-alpha production by PBM, and that fibroblasts are a good source of
      PGE2, we determined the content of PGE2 in the FCM used in our experiments. We
      found a good correlation (r = 0.949) between the amount of PGE2 produced by
      fibroblasts and the degree of TNF-alpha inhibition exerted. In addition, the
      inhibitory effect of FCM was mimicked by the addition to PBM cultures of
      exogenous PGE2 in amounts similar to those spontaneously released by fibroblasts
      in FCM. All of these data suggest a molecular and cellular interaction between
      PBM and fibroblasts that could contribute to those modulatory mechanisms involved
      in the self-limitation of the fibrotic process.

PMID- 8879180
TI  - Early regulatory changes in rat pulmonary artery of renin-dependent systemic
      hypertension models.
AB  - Patients with systemic hypertension of various etiologies maintain their
      pulmonary artery pressures within normal limits. We have reported in isolated
      perfused rat lungs that low basal tone appears to be regulated by nitric oxide
      (NO)-dependent and -independent mechanisms of soluble guanylate cyclase
      activation, and similar results are seen in isolated small pulmonary arteries
      (PA) from these animals. The abdominal aorta of rats was ligated above the left
      and below the right renal artery (aortic coarctation, AC). The mean arterial
      pressure (MAP) and pulmonary artery pressure (PAP) of 24-h post-AC rats (MAP 123
      +/- 7.1 mm Hg and PAP 4.2 +/- 0.9 mm Hg) showed no significant change when
      compared with those of sham control rats (MAP 116 +/- 7.0 mm Hg and PAP 5.0 +/-
      0.04 mm Hg). Hypoxic contractions in isolated small rat PA (160 to 260 microns
      diameter) were significantly increased from 56.7 +/- 12.0 mg in the control group
      to 139 +/- 31 mg in the 24-h post-AC rats (P < 0.05). PA contractions in the
      presence of 100 microM nitro-L-arginine (NLA) increased from 102 +/- 34 mg among
      the sham control group to 261 +/- 30 mg among the 24-h post AC rats (P < 0.05).
      After NLA, the hypoxic contractions decreased to 15 +/- 2.9 mg in the control
      rats and 45 +/- 16 mg in the 24-h post-AC rats when compared with pre-NLA values
      (P < 0.05). Western and Northern blotting of protein and messenger ribonucleic
      acid (mRNA) extracted from the whole rat lung showed a significant rise in
      endothelial cell nitric oxide synthase (EcNOS; 207 +/- 34%) and EcNOS mRNA (2
      fold) when comparing controls with 24-h post-AC rats. These data indicate that
      there is increased EcNOS activity and synthesis that maintain low PA tone in
      these rat models as early as 24 h after AC; in addition, this effect is
      independent of the systemic blood pressure.

PMID- 8879181
TI  - Human lung mast cell activation leads to IL-13 mRNA expression and protein
      release.
AB  - Using reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked
      immunosorbent assay (ELISA), we studied the generation of the recently described
      Th2 cytokine interleukin-13 (IL-13) by anti-IgE-activated lung fragments (LF),
      lung mast cells (LMC), and the mast cell line HMC-1. We found that IL-13
      messenger ribonucleic acid (mRNA) was constitutively expressed in LF and rapidly
      increased after anti-IgE challenge, persisting throughout a 16-h period.
      Quantitative-competitive PCR (QCPCR) demonstrated an increase from 1.2 fg to 120
      fg of IL-13 mRNA/micrograms LF total cellular RNA. Time-course experiments showed
      that IL-13 protein was not increased in supernatants at 2 h after activation, but
      was upregulated by 8 h. Anti-IgE-activated LF supernatants contained 592.1 +/-
      314.8 pg IL-13/g wet weight of tissue at 24 h (mean +/- SE; n = 11). LMC
      demonstrated upregulation of IL-13 mRNA expression following treatment with
      A23187 (n = 4), with maximal upregulation by 3 h; anti-IgE or phorbol myristate
      acetate (PMA) also led to increased IL-13 mRNA expression. QCPCR analysis of LMC
      IL-13 mRNA expression at 4 h after activation showed a 7-, 13.8-, and 13.2-fold
      increase after A23187, anti-IgE, and PMA, respectively. Quantities of IL-13
      released from optimally activated LMC and peripheral blood T cells were
      comparable. HMC-1 also showed enhanced IL-13 mRNA beginning 30 min after A23187
      activation, with peak expression from 1 to 10 h, followed by waning over the
      subsequent 24 h. A23187 stimulation of HMC-1 led to 100-fold upregulation of IL
      13 mRNA within 4 h and detectable IL-13 in 24-h supernatants. These results
      demonstrate that activation of LF and LMC through multiple signal-transduction
      pathways results in increased IL-13 mRNA and protein expression temporally
      consistent with a potential role in chronic allergic inflammation.

PMID- 8879182
TI  - Expression of laminins in the airways in various types of asthmatic patients: a
      morphometric study.
AB  - Laminins (Ln) are crucial in airway morphogenesis. Because they are able to
      interact with inflammatory cells, they are likely to participate in inflammation
      accompanied by airway structural remodeling in asthma. Taking biopsies and using
      immunohistochemistry and quantitative image analysis, we characterized the
      distribution of Ln chains alpha 1, alpha 2, and beta 2 in the bronchial mucosa of
      patients with seasonal (n = 17), early occupational (n = 8), and chronic asthma
      (n = 16) for comparison with that of normal controls (n = 8). In all asthmatic
      patients, both Ln chains alpha 1 and beta 2 were confined to the superficial
      margin of the basement membrane (BM), blood vessels, and smooth muscle. The
      thickness of Ln beta 2 expression in BM was significantly greater in patients
      with chronic (1.9 +/- 0.1 microns; P < 0.001) and occupational asthma (1.7 +/-
      0.1 microns; P < 0.05) than in controls (0.4 +/- 0.3 microns). Only in patients
      with occupational asthma was the thickness of the Ln alpha 1 layer (2.3 +/- 0.2
      microns; mean +/- SEM) significantly different from that in controls (1.4 +/- 0.5
      microns; P < 0.05). There was no immunoreactivity for the Ln alpha 2 chain in
      controls or patients with mild asthma, but in clinically severe chronic asthma we
      found a discontinuous staining along the epithelial margin of the BM. Since Ln
      chains alpha 2 and beta 2 appear to function only during morphogenesis, increased
      expression of these Ln chains in adult asthma patients suggests accelerated
      tissue turnover in the airways, possibly as a result of airway inflammation in
      asthma.

PMID- 8879183
TI  - Human SP-A locus: allele frequencies and linkage disequilibrium between the two
      surfactant protein A genes.
AB  - Two surfactant protein A (SP-A) genes and several alleles for each SP-A locus
      have been previously described. In this report we investigate the potential
      usefulness of the SP-A loci as markers for genetic studies. We establish
      conditions that allow the identification of alleles with very similar sequences;
      We also determine the degree of polymorphism for each SP-A locus: The
      heterozygosity and polymorphism information content (PIC) values for the SP-A1
      locus are 0.63 and 0.55, respectively, and for the SP-A2 locus are 0.50 and 0.56.
      In the course of these studies, we identify one new SP-A2 allele and show that
      the SP-A1 and SP-A2 loci are in linkage disequilibrium (P < 0.000001). We also
      identify 19 of the 20 possible haplotypes in a population of n = 239. Nine of the
      observed haplotypes reach statistical significance (P < 0.01) in this population,
      and the segregation of two haplotypes (6A2/1A0 and 6A4/1A) without recombination
      is verified in a family pedigree. These data together indicate that both SP-A
      loci are sufficiently polymorphic to be good markers for use in genetic studies.
      Furthermore, the finding of one novel allele suggests that additional unknown SP
      A alleles are yet to be found.

PMID- 8879184
TI  - Reversal of lung lesions in transgenic transforming growth factor alpha mice by
      expression of mutant epidermal growth factor receptor.
AB  - Transgenic mice expressing transforming growth factor alpha (TGF-alpha) in type
      II cells under control of the lung-specific surfactant protein-C (SP-C) promoter
      develop pulmonary fibrosis and marked airspace hypoplasia. To identify cellular
      signaling mechanisms involved in lesion formation, we generated transgenic mice
      expressing a mutant epidermal growth factor receptor lacking a portion of the
      intracytoplasmic domain (EGF-R-M) under control of the human SP-C promoter.
      Transcripts of the SP-C-EGF-R-M transgene were detected in distal bronchiolar and
      type II cells by in situ hybridization. The morphology of lungs from the SP-C-EGF
      R-M transgenic mice was normal. Lung fibrosis was not detectable and airspace
      hypoplasia was significantly corrected in bitransgenic mice derived by breeding
      SP-C-TGF-alpha and SP-C-EGF-R-M mice. Correction of lung pathology in the
      bitransgenic mice occurred without altering the level of hTGF-alpha mRNA. To
      further demonstrate that reversal of TGF-alpha lesions required signaling through
      the EGF-R, SP-C-TGF-alpha transgenic mice were bred to mice homozygous for the wa
      2 mutation which encodes a mutated EGF-R. TGF-alpha-induced lesions were reversed
      in homozygous wa-2 mice. Amelioration of TGF-alpha-dependent pulmonary lesions in
      SP-C-EGF-R-M mice or wa-2/wa-2 mice supports the concept that autocrine and
      paracrine signaling mediate fibrosis and airspace remodeling caused by TGF-alpha.

PMID- 8879185
TI  - Surfactant proteins A and D increase in response to intratracheal
      lipopolysaccharide.
AB  - Surfactant proteins A (SP-A) and D (SP-D) are "collectins": proteins with
      collagen-like region and lectin domain that bind carbohydrates in a calcium
      dependent manner. Mannose-binding protein, a serum collectin, is an acute-phase
      protein. We hypothesized that SP-A and SP-D would respond to an acute stress,
      such as lung inflammation, in the same manner as does mannose-binding protein,
      with increased messenger ribonucleic acid (mRNA) and protein production. Rats
      received intratracheal lipopolysaccharide (LPS; 0.5 mg/kg) or vehicle and were
      killed 1, 6, 24, and 72 h later. Their lungs were lavaged and the lung tissue
      homogenized and analyzed for SP-A, SP-D, and phospholipids. Tissue levels of SP-A
      were increased by 6 h, peaked at 24 h, and were still elevated at 72 h in LPS
      treated animals as compared with those given vehicle. SP-A and SP-D levels in
      lavage fluid were significantly elevated at 72 h. Message levels for SP-A and SP
      D, but not SP-B, were significantly increased at 24 h. Lavage phospholipid levels
      first increased, then decreased in both the control and LPS-treated animals, and
      significantly less phospholipid was recovered in the lavage fluid of the LPS
      treated animals than in that of controls at 72 h. Although other mechanisms,
      including altered surfactant metabolism, may be involved, these data are
      consistent with our hypothesis that SP-A and SP-D are upregulated by an acute
      inflammatory stress in a manner analogous to that of the structurally and
      functionally related serum acute-phase reactant, mannose-binding protein. We
      speculate that this upregulation may be a protective response for the lungs.

PMID- 8879186
TI  - A transformed human tracheal gland cell line, MM-39, that retains serous
      secretory functions.
AB  - Infection with the wild type SV40 virus was used to transform primary cultures of
      human tracheal gland serous (HTGS) cells. Over 80 different cell lines were
      obtained, but the majority had lost some of their epithelial and secretory
      features. However, one of these cell lines, MM-39, was shown to have conserved
      the physiologic characteristics of the genuine HTGS cells-i.e., the presence of
      cytokeratin, expression of cystic fibrosis transmembrane conductance regulator
      mRNA, a level of secretory leukocyte proteinase inhibitor secretion comparable to
      that of the native cells (25 +/- 3 ng/10(6) cells/h), and the responsiveness to
      pharmacological agonists: carbachol (+260 +/- 40%), isoproterenol (+260 +/- 40%),
      and adenosine 5'-triphosphate (+280 +/- 30%). These characteristics describe a
      transformed cell line of human tracheal gland cells which has retained the
      features of the native serous cells. As a result, this cell line appears to be a
      useful tool for large-scale physiologic and pharmacologic studies of bronchial
      secretion at the cellular level.

PMID- 8879187
TI  - Microanatomy of secretory granule release from guinea pig tracheal goblet cells.
AB  - The microanatomy of mucin granule release from epithelial goblet cells has been
      investigated in guinea pig tracheae. Using a tannic acid arrest procedure,
      granule release under basal conditions and after high K+ or acetylcholine (ACh)
      application was arrested and a variety of granule fusion sites were identified in
      ultrathin sections and freeze-fracture replicas. Rather than there being
      subclasses of secretory cells containing either electron-lucent granules
      (indicative of mucin) or smaller electron-dense (serous) granules, the majority
      of secretory cells in both control and treated groups contained granules with an
      electrondense core surrounded by an electron-lucent region. Granule release sites
      were of three principal types: (1) simple exocytosis, where the membranes of
      single granules fused directly with the plasma membrane to give an "omega"
      profile; (2) compound exocytosis, where granule membranes, fused together
      intracellularly, were found in continuity with the plasma membrane; and (3)
      apocrine-like secretion, which involved the loss of the central apical mass of
      granules together with elements of the cell cytoplasm. In treated preparations,
      there was an increase in the number of cells exhibiting fusion sites; the
      percentage showing simple fusions fell from 82% to 59% (with ACh) and 57% (with
      KCl), whereas the percentage of cells exhibiting compound and apocrine-like
      secretion increased. Dense cores were frequently retained at the sites of fusion
      and, despite the expansive decondensation of mucin known to occur, there was also
      evidence of some retention of the electron-lucent material.

PMID- 8879188
TI  - Contrasting response of lung parenchymal cells to instilled TNF alpha and IFN
      gamma: the inducibility of specific cell ICAM-1 in vivo.
AB  - Induction of intercellular adhesion molecule-1 (ICAM-1) by proinflammatory
      cytokines during inflammation plays an important role in regulating
      polymorphonuclear neutrophil (PMN) migration and localization. In this report, we
      examined the effects of tumor necrosis factor-alpha (TNF alpha) and interferon
      gamma (IFN gamma) on specific lung cell expression of ICAM-1 in vivo and the
      accompanying morphological changes. Balb-c mice were treated with phosphate
      buffered saline (PBS) alone or with PBS containing 5 micrograms TNF alpha or IFN
      gamma through intranasal instillation. Twenty-four hours after treatment, their
      lungs were processed for immunoblot analysis and electron microscope
      immunocytochemistry. In the normal lung, the ICAM-1 level is high on type I
      alveolar epithelial cells, medium on arterial and venous endothelial cells, low
      on type II epithelial cells and capillary endothelium, and not detectable on
      bronchial epithelium. Topical treatment of the lung with either TNF alpha or IFN
      gamma induced a 50-60% increase in total lung and alveolar ICAM-1. A dramatic
      increase of alveolar type II cell surface ICAM-1 was observed (> 20-fold). Both
      cytokines caused 2-3-fold higher ICAM-1 expression on capillary endothelial cells
      and a 40% increase of ICAM-1 on alveolar type I cells that was not uniform.
      However, due to the large total surface area of type I epithelium, type I cells
      contribute 70-86% of total alveolar septal ICAM-1 and > 90% of alveolar surface
      ICAM-1 in either treated or normal mouse lungs. Increased ICAM-1 expression was
      also observed on nonparenchymal endothelial and epithelial cells. Margination and
      sequestration of PMN in cytokine-treated lungs were observed by histologic
      examination, measurements of total lung myloperoxidase activity, and number of
      neutrophils recovered in bronchoalveolar lavage fluid. These results showed that
      TNF alpha and IFN gamma induce ICAM-1 expression and infiltration of neutrophils
      in the lung. The response of specific lung cells in terms of induction of ICAM-1
      in response to cytokine stimulation varied significantly, particularly between
      type I and type II epithelial cells.

PMID- 8879189
TI  - Different roles for PDGF-alpha and -beta receptors in embryonic lung development.
AB  - Platelet-derived growth factor (PDGF) is implicated in the process of normal lung
      development. We have previously shown the presence of PDGF-AA and BB homodimers
      in embryonic rat lung. Also, we reported that PDGF-AA is involved in embryonic
      lung branching, whereas PDGF-BB influences embryonic lung growth. PDGF isoforms
      bind with different affinities to two related receptors, denoted the PDGF alpha-
      and beta-receptors, respectively. The alpha-receptor binds both PDGF isoforms,
      whereas the beta-receptor binds only PDGF-BB. In the present study, we
      investigated the role of both receptors in early embryonic rat lung development.
      Reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that
      both PDGF alpha- and beta-receptor mRNAs are mainly expressed in the mesenchyme.
      Phosphorothioate antisense receptor oligonucleotides decreased PDGF receptor mRNA
      expression in early lung explants. PDGF-induced receptor tyrosine phosphorylation
      was also reduced by the antisense oligonucleotides. Incubation of embryonic lung
      explants with antisense beta-receptor oligonucleotides inhibited lung growth but
      not early lung branching. Neither growth nor branching were affected by sense
      beta-receptor oligonucleotides. The inhibitory effect of antisense beta-receptor
      oligonucleotides on embryonic lung growth was reversed by the addition of PDGF-BB
      or PDGF-AA, suggesting that the alpha-receptor can transduce similar mitogenic
      signals as the beta-receptor in early lung development. Antisense alpha-receptor
      oligonucleotides reduced both embryonic lung growth and branching. Sense alpha
      receptor treatment had no effect on lung growth and branching. PDGF-BB but not
      PDGF-AA partially attenuated the inhibitory effect of antisense alpha-receptor
      oligonucleotides on lung growth. In contrast, PDGF-BB did not overcome the
      inhibitory effect on early lung branching, indicating that the beta-receptor
      cannot replace this biologic role of the alpha-receptor in early lung
      development. These data suggest that PDGF-BB stimulation of both receptors leads
      to lung growth, whereas PDGF-AA stimulation of the alpha-receptor induces
      transduction pathways that lead lung branching.

PMID- 8879190
TI  - Whence the intestinal intraepithelial lymphocyte?

PMID- 8879191
TI  - Mutant mice without B lymphocyte follicles.

PMID- 8879192
TI  - Human leukocyte elastase is an endogenous ligand for the integrin CR3
      (CD11b/CD18, Mac-1, alpha M beta 2) and modulates polymorphonuclear leukocyte
      adhesion.
AB  - Integrin CR3 (CD11b/CD18, Mac-1, alpha M beta 2) mediates the transient adhesion
      of polymorphonuclear leukocytes (PMN) to surfaces coated with fibrinogen, C3bi,
      ICAM-1, and other ligands. Recent studies (Cai, T.-Q., and S.D. Wright 1995. J.
      Biol. Chem. 270:14358) suggest that adhesion may be favored by stimulus-dependent
      changes in the kinetics of ligand binding by CR3. Cell detachment, on the other
      hand, must occur by a different mechanism because binding kinetics cannot affect
      cell adhesion after binding of ligand has occurred. We have sought a mechanism
      that would reverse binding of ligand to CR3 and report here that lysates of PMN
      contain an endogenous ligand that binds CR3 and competes the binding of C3bi.
      Purification and sequence analysis identified the structurally homologous
      azurophilic granule proteins, elastase, protease 3, and azurocidin as candidates.
      Studies with purified elastase and azurocidin showed that each bound specifically
      to purified, immobilized CR3. Elastase may play a role in modulating integrin
      mediated cell adhesion because it is expressed at the cell surface, and the
      expression level is inversely proportional to cell adhesivity. Furthermore, a
      monoclonal antibody against elastase prevented detachment of PMN from fibrinogen
      coated surfaces and blocked chemotaxis, confirming a role for this protein in
      regulating integrin-mediated adhesion. These studies suggest a model for release
      of integrin-mediated cell adhesion in which endogenous ligands such as elastase
      may release adhesion by "'eluting" substrate-bound ligand. A role for the
      proteolytic activity of elastase appears likely but is not demonstrated in this
      study.

PMID- 8879193
TI  - Interaction between complement proteins C5b-7 and erythrocyte membrane sialic
      acid.
AB  - The initial phase of membrane attack by complement is the interaction between
      C5b6, C7, and the cell membrane that leads to the insertion of C5b-7. Here we
      investigate the role of sialic acid residues in the assembly of C5b-7
      intermediates on erythrocyte cell membranes. We find that C5b6 binds to
      glycophorin, whereas C5 or C6 does not bind, and desialylation of the glycophorin
      abolishes C5b6 binding. Complement lysis is inhibited by either masking
      glycophorin sialic acid with F(ab) fragments of an mAb, or by removal of the
      sialylated region of glycophorin by mild trypsinization. Gangliosides inhibit C5b
      7 deposition when added to the aqueous phase. Asialogangliosides and synthetic
      gangliosides lacking the carboxylic acid residue have no inhibitory activity. We
      conclude that C5b6 binds to sialylated molecules on the erythrocyte surface. We
      propose a new model of membrane attack in which C5b6 initially binds to membranes
      via ionic forces. C7 then binds to C5b6, disrupting the ionic interaction and
      leading to the exposure of hydrophobic domains. Sialic acid is known to inhibit
      complement activation. Thus, these findings reveal a paradoxical role for sialic
      acid in complement attack; the presence of sialic acid inhibits the generation of
      C5b6, but once the membrane attack pathway is initiated, sialic acid enhances
      complement lysis.

PMID- 8879194
TI  - Conservation of the lipooligosaccharide synthesis locus lgt among strains of
      Neisseria gonorrhoeae: requirement for lgtE in synthesis of the 2C7 epitope and
      of the beta chain of strain 15253.
AB  - The present study was undertaken to examine the extent to which the lgt locus
      varies among strains of gonococci. This locus encodes five glycosyl transferases
      involved in the synthesis of the lipooligosaccharide (LOS) of Neisseria
      gonorrhoeae. We examined seven gonococcal strains and found that the structure of
      the lgt locus is conserved among six of these strains. The locus is strikingly
      altered in strain 15253. This is one of the few strains where extensive
      structural analysis of its LOS is available, and therefore, we defined the
      altered lgt locus and focused on the reactivity of mAB 2C7. We found that strain
      15253 contains only two lgt genes, lgtA and lgtE. As in F62, lgtA encodes a
      GlcNAc transferase and is subject to phase variation. In addition, by analysis of
      deletion mutants, we found that lgtE, which encodes a galactosyl transferase that
      is required for elongating the alpha-chain, is also necessary for completing the
      beta chain.

PMID- 8879195
TI  - Disturbed interaction of p21-rac with mutated p67-phox causes chronic
      granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is characterized by the failure of phagocytic
      leukocytes to generate superoxide, needed for the intracellular killing of
      microorganisms. This is caused by mutations in any one of the four subunits of
      the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In a rare,
      autosomal recessive form of CGD, a 67-kD cytosolic component of this enzyme (p67
      phox) is missing. We here report on a patient with a mutation in the p67-phox
      gene that leads to expression of a nonfunctional p67-phox protein. The purified
      granulocytes of this patient failed to produce superoxide and contained about
      half of the normal amount of p67-phox. Analysis of the cDNA and genomic DNA of
      this patient showed that the patient is a compound heterozygote for a triplet
      nucleotide deletion in the p67-phox gene, predicting an in-frame deletion of
      lysine 58 in the p67-phox protein and a larger deletion of 11-13 kb in the other
      allele. Interestingly, the 58Lys deletion in p67-phox disrupts the interaction
      with p21-rac1, a ras-related protein involved in the activation of the NADPH
      oxidase. In contrast to normal neutrophils, in which p47-phox and p67-phox
      translocate to the plasma membrane upon cell activation, the cells of the patient
      did not show this translocation, indicating that an interaction between p67-phox
      and p21-rac1 is essential for translocation of these cytosolic proteins and
      activation of the NADPH oxidase. Moreover, this CGD patient represents the first
      case of disease caused by a disturbed binding of a ras-related protein to its
      target protein.

PMID- 8879196
TI  - A T cell receptor V alpha domain expressed in bacteria: does it dimerize in
      solution?
AB  - To evaluate the potential for dimerization through a particular T cell receptor
      (TCR) domain, we have cloned the cDNA encoding a TCR V alpha from a hybridoma
      with specificity for the human immunodeficiency virus (HIV) envelope glycoprotein
      120-derived peptide P18-110 (RGPGRAFVTI) bound to the murine major
      histocompatibility complex (MHC) class I molecule, H-2Dd. This cDNA was then
      expressed in a bacterial vector, and protein, as inclusion bodies, was
      solubilized, refolded, and purified to homogeneity. Yield of the refolded
      material was from 10 to 50 mg per liter of bacterial culture, the protein was
      soluble at concentrations as high as 25 mg/ml, and it retained a high level of
      reactivity with an anti-V alpha 2 monoclonal antibody. This domain was monomeric
      both by size exclusion gel chromatography and by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Circular dichroism spectra indicated that the
      folded V alpha domain had secondary structure similar to that of single
      immunoglobulin or TCR domains, consisting largely of beta sheet. Conditions for
      crystallization were established, and at least two crystal geometries were
      observed: hexagonal bipyramids that failed to diffract beyond approximately 6 A,
      and orthorhombic crystals that diffracted to 2.5 A. The dimerization of the V
      alpha domain was investigated further by solution nuclear magnetic resonance
      spectroscopy, which indicated that dimeric and monomeric forms of the protein
      were about equally populated at a concentration of 1 mM. Thus, models of TCR
      mediated T cell activation that invoke TCR dimerization must consider that some V
      alpha domains have little tendency to form homodimers or multimers.

PMID- 8879197
TI  - Structural basis for T cell recognition of altered peptide ligands: a single T
      cell receptor can productively recognize a large continuum of related ligands.
AB  - T cells recognize short linear peptides bound to major histocompatibility complex
      (MHC)-encoded molecules. Subtle molecular changes in peptide antigens produce
      altered peptide ligands (APLs), which induce different T cell responses from
      those induced by the antigenic ligand. A molecular basis for how these slight
      molecular variations lead to such different consequences for the T cell has not
      been described. To address this issue, we have made amino acid substitutions at
      the primary T cell receptor (TCR) contact residue of the murine hemoglobin
      determinant, Hb(64-76)/I-Ek and produced 12 peptides that interact with the TCR
      of the T cell clone 3.L2. The 3.L2 T cell responds to these peptides, which vary
      1 million-fold in their activity, and enables them to be ranked according to
      their relative ability to signal through the 3.L2 TCR. Such a ranking reveals
      that the ability of the 3.L2 T cell to respond to these peptides depends on how
      well the structure of the side chain at the primary TCR contact site mimics that
      of the Asn residue present in the antigenic ligand. The reactivity of the 3.L2 T
      cell also depends on an MHC contact residue that is next to the primary TCR
      contact residue, suggesting that conformation of the Asn side chain is also
      important. By using nonnatural amino acids at a TCR contact residue, we have
      demonstrated that APLs can be rationally designed based on structure. These data
      are consistent with a model in which the affinity of a peptide-MHC complex for
      the TCR determines how the T cell will respond.

PMID- 8879198
TI  - A disease-related rheumatoid factor autoantibody is not tolerized in a normal
      mouse: implications for the origins of autoantibodies in autoimmune disease.
AB  - We have analyzed B cell tolerance in a rheumatoid factor (RF) transgenic mouse
      model. The model is based on AM14, a hybridoma, originally isolated from an
      autoimmune MRL/lpr mouse that has an affinity and specificity typical of disease
      related RFs from this strain. AM14 binds to immunoglobulin (Ig)G2a of the "a"
      allotype (IgG2aa) and not to IgG2ab. Thus, by crossing the transgenes onto an
      IgHa (BALB/c) background or to a congenic IgHb (CB.17) background, we could study
      the RF-expressing B cells when they were self-specific (IgHa) or when they were
      not self-specific (IgHb). These features make the AM14 model unique in focusing
      on a true autoantibody specificity while at the same time allowing comparison of
      autoreactive and nonautoreactive transgenic B cells, as was possible in model
      autoantibody systems such as anti-hen egg lysozyme. Studies showed that AM14 RF B
      cells can make primary immune responses and do not downregulate sIgM, indicating
      that the presence of self-antigen does not induce anergy of these cells. In fact,
      IgHa AM14 transgenic mice have higher serum levels of transgene-encoded RF than
      their IgHb counterparts, suggesting that self-antigen-specific activation occurs
      even in the normal mouse background. Since AM14 B cells made primary responses,
      we had the opportunity to test for potential blocks to self-reactive cells
      entering the memory compartment. We did not find evidence of this, as AM14 B
      cells made secondary immune responses as well. These data demonstrate that a
      precursor of a disease-specific autoantibody can be present in the preimmune
      repertoire and functional even to the point of memory cell development of normal
      mice. Therefore, immunoregulatory mechanisms that normally prevent autoantibody
      production must exert their effects later in B cell development or through T cell
      tolerance. Conversely, the data suggest that it is not necessary to break central
      tolerance, even in an autoimmune mouse, to generate pathologic, disease
      associated autoantibodies.

PMID- 8879199
TI  - CD5 is a potential selecting ligand for B cell surface immunoglobulin framework
      region sequences.
AB  - In rabbits nearly all B lymphocytes express the glycoprotein CD5, in contrast to
      mice and humans, where only a small proportion of B cells express this molecule
      (Raman, C., and K.L. Knight. 1992. J. Immunol. 149:3858-3864). CD5+ B cells
      appear to develop early in ontogeny and be maintained throughout life by self
      renewal. The function of CD5 on B cells is still unknown. We showed earlier that
      "positive" selection occurs during B lymphocyte development in the rabbit
      appendix. This selection favors B cell expressing surface immunoglobulins with
      VHa2 structures in the first and third framework regions (Pospisil, R., G.O.
      Young-Cooper, and R.G. Mage. 1995. Proc. Natl. Acad. Sci. USA. 92:6961-6965).
      Here we report that F(ab')2 fragments, especially those bearing VHa2 framework
      region determinants, specifically interact with the B cell-surface glycoprotein
      CD5. This interaction can be inhibited by anti-CD5 antibodies. Furthermore,
      immobilized F(ab')2 fragments selectively bind CD5 molecules in appendix cell
      lysates. Interactions of VH framework region structures with CD5 may affect
      maintenance and selective expansion of particular B cells and thus contribute to
      autostimulatory growth of autoimmune or transformed cells.

PMID- 8879200
TI  - Increased interleukin 4 and immunoglobulin E production in transgenic mice
      overexpressing NK1 T cells.
AB  - Natural Killer (NK)1.1+ (NK1) T cells are a specialized subset of alpha/beta T
      cells that coexpress surface receptors that are normally associated with the NK
      cell lineage of the innate immune system. On recognition of the conserved, major
      histocompatibility complex class I-like CD1 molecule, these cells are able to
      release explosive bursts of interleukin 4 (IL-4), a cytokine that promotes the T
      helper type 2 (Th2) effector class of an immune response. A unique feature of
      their T cell receptor (TCR) repertoire is the expression of an invariant TCR
      alpha chain, V alpha 14-J alpha 281, and of a restricted but polyclonal set of V
      beta gene families, V beta 8, V beta 7, and V beta 2. Here, we show that
      transgenic expression of this TCR alpha chain during thymic development is
      sufficient information to bias the differentiation of mainstream thymocytes
      towards the NK1 developmental pathway. It markedly increases the frequency of
      cells with the NK1 pattern of T cell differentiation and also has drastic
      consequences for the selection of the V beta repertoire. Transgenic CD4 cells
      exhibited a 10-100-fold increase in IL-4 production on mitogen stimulation in
      vitro and in vivo, and baseline levels of the Th2-controlled serum immunoglobulin
      isotypes, IgE and IgG1, were also selectively elevated in vivo.

PMID- 8879201
TI  - Beta 2-microglobulin-dependent NK1.1+ T cells are not essential for T helper cell
      2 immune responses.
AB  - A number of investigations have established the critical role of interleukin 4
      (IL-4) in mediating the development of T helper (Th)2 effector cells in vitro and
      in vivo. Despite intensive study, the origin of the IL-4 required for Th2 priming
      and differentiation remains unclear. Natural killer (NK)1.1+ alpha/beta T cell
      receptor+ T(NT) cells, a unique lineage of cells capable of producing large
      amounts of IL-4 after activation in vivo, are important candidates for directing
      Th2 priming. These cells are selected by the nonpolymorphic major
      histocompatibility complex (MHC) class I molecule, CD1, and are deficient in beta
      2-microglobulin (beta 2m)-null mice. We used beta 2m-deficient mice on both
      BALB/c and C57BL/6 backgrounds to examine their capacity to mount Th2 immune
      responses after challenge with a number of well-characterized antigens
      administered by a variety of routes. As assessed by immunization with protein
      antigen, infection with Leishmania major, embolization with eggs of Schistosoma
      mansoni, intestinal infection with Nippostrongylus brasiliensis, or induction of
      airway hyperreactivity to aerosolized antigen, beta 2m-deficient mice developed
      functional type 2 immune responses that were not substantially different than
      those in wild-type mice. Production of IL-4 and the generation of immunoglobulin
      E (IgE) and eosinophil responses were preserved as assessed by a variety of
      assays. Collectively, these results present a comprehensive analysis of type 2
      immune responses in beta 2m-deficient mice, and indicate that beta 2m-dependent
      NT cells are not required for Th2 development in vivo.

PMID- 8879202
TI  - Colony growth of human hematopoietic progenitor cells in the absence of serum is
      supported by a proteinase inhibitor identified as antileukoproteinase.
AB  - Serum contains many growth factors and nutrients that stimulate colony formation
      of hematopoietic progenitor cells (HPC) in semisolid cultures. In the absence of
      serum, no proliferation of HPCs could be obtained in semisolid medium cultures of
      partially purified bone marrow cells in the presence of multiple hematopoietic
      growth factors, insulin, cholesterol, and purified clinical-grade human albumin.
      This appeared to be due to a suppressive activity induced by monocyte- and T
      lymphocyte-depleted accessory cells on CD34+ HPCs. Serum-free conditioned medium
      from the bladder carcinoma cellline 5637 could replace serum to support the
      growth of HPCs in these cultures. After gel filtration and reverse-phase high
      performance liquid chromatography of 5637 supernatants, this activity could be
      attributed to a 15-kD protein that was further identified by NH2-terminal
      sequence analysis as the serine proteinase inhibitor antileukoproteinase (ALP).
      The growth-supportive activity from the 5637 conditioned medium and the
      (partially) purified fractions could be completely neutralized by a polyclonal
      rabbit IgG antibody against human ALP (huALP). Similar supportive effects on the
      growth of HPC could be obtained in the presence of recombinant huALP. We
      demonstrated that the COOH-terminal domain of ALP containing the proteinase
      inhibitory activity was responsible for this effect. alpha-1 proteinase inhibitor
      was capable of similar support of in vitro HPC growth. These results illustrate
      that proteinase inhibitors play an important role in the in vitro growth of
      hematopoietic cells by the neutralization of proteinases produced by bone marrow
      accessory cells. This may be of particular relevance for in vitro expansion of
      human hematopoietic stem cells in serum-free media.

PMID- 8879203
TI  - Proteasome alpha-type subunit C9 is a primary target of autoantibodies in sera of
      patients with myositis and systemic lupus erythematosus.
AB  - Autoantibodies occur in low frequencies among patients with myositis
      characterizing only distinct subsets of this disease. Most of these known
      antibodies are directed to enzymatically active complexes. The 20S proteasome
      represents an essential cytoplasmatic protein complex for intracellular
      nonlysosomal protein degradation, and is involved in major histocompatibility
      complex class I restricted antigen processing. In this study we investigated
      whether the 20S proteasome complex is an antibody target in myositis and in other
      autoimmune diseases. 34 sera of poly/dermatomyositis patients were assayed for
      antiproteasomal antibodies using enzyme-linked immunosorbent assay, immunoblot,
      and two-dimensional non-equilibrium pH gradient electrophoresis (NEPHGE). Sera
      was from patients with systemic lupus erythematosus (SLE), mixed connective
      tissue disease, and rheumatoid arthritis; healthy volunteers served as controls.
      In 62% (21/34) of the cases sera from patients with myositis and in 58% (30/52)
      of the cases sera from patients with SLE reacted with the 20S proteasome. These
      frequencies exceeded those of sera from patients with mixed connective tissue
      disease, rheumatoid arthritis, and healthy controls. The alpha-type subunit C9 of
      the 20S proteasome was determined to be the predominant target of the autoimmune
      sera in myositis and SLE. Lacking other frequent autoantibodies in myositis, the
      antiproteasome antibodies are the most common humoral immune response so far
      detected in this disease entity.

PMID- 8879204
TI  - Ribosomal scanning past the primary initiation codon as a mechanism for
      expression of CTL epitopes encoded in alternative reading frames.
AB  - An increasing amount of evidence has shown that epitopes restricted to MHC class
      I molecules and recognized by CTL need not be encoded in a primary open reading
      frame (ORF). Such epitopes have been demonstrated after stop codons, in
      alternative reading frames (RF) and within introns. We have used a series of
      frameshifts (FS) introduced into the Influenza A/PR/8 /34 nucleoprotein (NP) gene
      to confirm the previous in vitro observations of cryptic epitope expression, and
      show that they are sufficiently expressed to prime immune responses in vivo. This
      presentation is not due to sub-dominant epitopes, transcription from cryptic
      promoters beyond the point of the FS, or internal initiation of translation. By
      introducing additional mutations to the construct exhibiting the most potent
      presentation, we have identified initiation codon readthrough (termed scanthrough
      here, where the scanning ribosome bypasses the conventional initiation codon,
      initiating translation further downstream) as the likely mechanism of epitope
      production. Further mutational analysis demonstrated that, while it should
      operate during the expression of wild-type (WT) protein, scanthrough does not
      provide a major source of processing substrate in our system. These findings
      suggest (i) that the full array of self- and pathogen-derived epitopes available
      during thymic selection and infection has not been fully appreciated and (ii)
      that cryptic epitope expression should be considered when the specificity of a
      CTL response cannot be identified or in therapeutic situations when conventional
      CTL targets are limited, as may be the case with latent viral infections and
      transformed cells. Finally, initiation codon readthrough provides a plausible
      explanation for the presentation of exocytic proteins by MHC class I molecules.

PMID- 8879205
TI  - Bcl-2 inhibits the mitochondrial release of an apoptogenic protease.
AB  - Bcl-2 belongs to a family of apoptosis-regulatory proteins which incorporate into
      the outer mitochondrial as well as nuclear membranes. The mechanism by which the
      proto-oncogene product Bcl-2 inhibits apoptosis is thus far elusive. We and
      others have shown previously that the first biochemical alteration detectable in
      cells undergoing apoptosis, well before nuclear changes become manifest, is a
      collapse of the mitochondrial inner membrane potential (delta psi m), suggesting
      the involvement of mitochondrial products in the apoptotic cascade. Here we show
      that mitochondria contain a pre-formed approximately 50-kD protein which is
      released upon delta psi m disruption and which, in a cell-free in vitro system,
      causes isolated nuclei to undergo apoptotic changes such as chromatin
      condensation and internucleosomal DNA fragmentation. This apoptosis-inducing
      factor (AIF) is blocked by N-benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (Z
      VAD.fmk), an antagonist of interleukin-1 beta-converting enzyme (ICE)-like
      proteases that is also an efficient inhibitor of apoptosis in cells. We have
      tested the effect of Bcl-2 on the formation, release, and action of AIF. When
      preventing mitochondrial permeability transition (which accounts for the pre
      apoptotic delta psi m disruption in cells), Bcl-2 hyperexpressed in the outer
      mitochondrial membrane also impedes the release of AIF from isolated mitochondria
      in vitro. In contrast, Bcl-2 does not affect the formation of AIF, which is
      contained in comparable quantities in control mitochondria and in mitochondria
      from Bcl-2-hyperexpressing cells. Furthermore, the presence of Bcl-2 in the
      nuclear membrane does not interfere with the action of AIF on the nucleus, nor
      does Bcl-2 hyperexpression protect cells against AIF. It thus appears that Bcl-2
      prevents apoptosis by favoring the retention of an apoptogenic protease in
      mitochondria.

PMID- 8879206
TI  - GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on
      naive peripheral lymphocytes.
AB  - Naive T cells are selectively recruited from the blood into peripheral lymph
      nodes during lymphocyte recirculation. L-selectin, a lectin-like receptor,
      mediates the initial attachment of lymphocytes to high endothelial venules (HEV)
      in lymph nodes. A subsequent step involving the activation of beta 2 integrins
      has been proposed to facilitate firm adhesion, but the activating signals are
      poorly understood. We report here that either antibody-mediated cross-linking of
      L-selectin on human lymphocytes or treatment of the cells with GlyCAM-1, an HEV
      derived, secreted ligand for L-selectin, stimulates their binding to ICAM-1
      through the beta 2 integrin pathway. Furthermore, GlyCAM-1 causes the rapid
      expression of a neoepitope on beta 2 integrins associated with a high-avidity
      state. Naive (CD45RA+), but not memory (CD45R0+) lymphocytes, respond to L
      selectin cross-linking or GlyCAM-1 treatment. Thus, the complexing of L-selectin
      by specific ligands may provide key signals to naive lymphocytes, contributing to
      their selective recruitment into peripheral lymphoid organs.

PMID- 8879207
TI  - The Mycobacterium tuberculosis phagosome interacts with early endosomes and is
      accessible to exogenously administered transferrin.
AB  - Previous studies have demonstrated that the Mycobacterium tuberculosis phagosome
      in human monocyte-derived macrophages acquires markers of early and late
      endosomes, but direct evidence of interaction of the M. tuberculosis phagosome
      with the endosomal compartment has been lacking. Using the cryosection immunogold
      technique, we have found that the M. tuberculosis phagosome acquires exogenously
      added transferrin in a time-dependent fashion. Near-maximal acquisition of
      transferrin occurs within 15 min, kinetics of acquisition consistent with
      interaction of the M. tuberculosis phagosome with early endosomes. Transferrin is
      chased out of the M. tuberculosis phagosome by incubation of the infected
      macrophages in culture medium lacking human transferrin. Phagosomes containing
      latex beads or heat-killed M. tuberculosis, on the other hand, do not acquire
      staining for transferrin. These and other findings demonstrate that M.
      tuberculosis arrests the maturation of its phagosome at a stage at which the
      phagosome interacts with early and late endosomes, but not with lysosomes. The
      transferrin endocytic pathway potentially provides a novel route for targeting
      antimicrobials to the M. tuberculosis phagosome.

PMID- 8879208
TI  - Analysis of interleukin 6 receptor and gp130 expressions and proliferative
      capability of human CD34+ cells.
AB  - We recently demonstrated that stimulation of gp130 by a combination of soluble
      interleukin 6 receptor (sIL-6R) and IL-6 but not IL-6 alone significantly
      stimulates the ex vivo expansion of primitive hematopoietic progenitors and the
      generation of erythroid cells from human CD34+ cells in the presence of stem cell
      factor (SCF). Here, we show that gp130 is found low positively on most CD34+
      cells, whereas IL-6R is expressed on only 30-50% of these cells. Although most of
      the colonies generated from FACS-sorted CD34+IL-6R+ cells were
      granulocyte/macrophage (GM) colonies, CD34+IL-6R- cells gave rise to various
      types of colonies, including erythroid bursts, GM, megakaryocytes, and mixed
      colonies in methylcellulose culture with a combination of IL-6, sIL-6R, and SCF.
      Similar results were obtained in culture supplemented with a combination of IL-3,
      IL-6, SCF, granulocyte colony-stimulating factor, erythropoietin, and
      thrombopoietin. A limiting dilution analysis of long-term culture-initiating
      cells (LTC-IC) showed that the CD34+IL-6R- cells contained a larger number of LTC
      IC than did the CD34+IL-6R+ cells. In a serum-free suspension of CD34+IL-6R-
      cells, the addition of sIL-6R to the combination of IL-6 and SCF dramatically
      increased the total and multipotential progenitors, whereas CD34+IL-6R+ cells
      failed to do so under the same conditions. These results indicate that most of
      the erythroid, megakaryocytic, and primitive human hematopoietic progenitors are
      included in the IL-6R- populations, and the activation of gp130 on these
      progenitors can be achieved by a complex of IL-6-sIL-6R, but not by IL-6 alone.
      The present culture system using IL-6, sIL-6R, and SCF may provide a novel
      approach for ex vivo expansion of human primitive hematopoietic progenitors.

PMID- 8879209
TI  - Structure and function of Cas-L, a 105-kD Crk-associated substrate-related
      protein that is involved in beta 1 integrin-mediated signaling in lymphocytes.
AB  - Integrin/ligand binding evokes tyrosine phosphorylation of various proteins. We
      reported previously that a 105 kD protein (pp105) was tyrosine phosphorylated by
      the engagement of beta 1 integrins in T lymphocytes. We show here that pp105 is a
      novel p130Cas (Crk-associated substrate)-related protein. Deduced amino acid
      sequence revealed that pp105 contains conserved motifs with p130Cas, and both
      pp105 and p130Cas bind to focal adhesion kinase (pp125FAK) and Crk. However,
      pp105 has a clearly distinct structure from p130Cas, and pp105 is preferentially
      expressed in lymphocytes, whereas p130Cas is expressed in adherent cells. With
      these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we
      demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck,
      and SHPTP2 to pp105. These findings further define the roles of pp105/Cas-L and
      pp125FAK in the integrin-mediated signaling pathways.

PMID- 8879210
TI  - Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating
      factor production in chronic myelomonocytic leukemia cells.
AB  - Autonomous release of hematopoietic growth factors may play a crucial role in the
      pathogenesis of certain hematological malignancies. Because of its cytokine
      synthesis-inhibiting action, interleukin 10 (IL-10) could be a potentially useful
      molecule to affect leukemic cell growth in such disorders. Chronic myelomonocytic
      leukemia (CMML) cells spontaneously form myeloid colonies (colony-forming units
      granulocyte/macrophage) in methylcellulose, suggesting an autocrine growth factor
      mediated mechanism. We studied the effect of recombinant human IL-10 (rhIL-10) on
      the in vitro growth of mononuclear cells obtained from peripheral blood or bone
      marrow of patients with CMML. IL-10 specifically binding to leukemic cells had a
      profound and dose-dependent inhibitory effect on autonomous in vitro growth of
      CMML cells. IL-10 significantly inhibited the spontaneous growth of myeloid
      colonies in methylcellulose in 10/11 patients, and autonomous CMML cell growth in
      suspension in 5/5 patients tested. Spontaneous colony growth from CMML cells was
      also markedly reduced by addition of antigranulocyte/macrophage colony
      stimulating factor (GM-CSF) antibodies, but not by addition of antibodies against
      G-CSF, IL-3, or IL-6, IL-10-induced suppression of CMML cell growth was reversed
      by the addition of exogenous GM-CSF and correlated with a substantial decrease in
      GM-CSF production by leukemic cells, both at the mRNA and protein levels. Our
      data indicate that IL-10 profoundly inhibits the autonomous growth of CMML cells
      in vitro most likely through suppression of endogenous GM-CSF release. This
      observation suggests therapeutic evaluation of rhIL-10 in patients with CMML.

PMID- 8879211
TI  - Innervation of melanocytes in human skin.
AB  - Communication between the nervous system and epidermal melanocytes has been
      suspected on the basis of their common embryologic origin and apparent parallel
      involvement in several disease processes, but never proven. In this study,
      confocal microscopic analysis of human skin sections stained with antibodies
      specific for melanocytes and nerve fibers showed intraepidermal nerve endings in
      contact with melanocytes. This intimate contact was confirmed by electron
      microscopy, which further demonstrated thickening of apposing plasma membranes
      between melanocytes and nerve fibers, similar to synaptic contacts seen in
      nervous tissue. Since many intraepidermal nerve fibers are afferent nerves that
      act in a "neurosecretory" fashion through their terminals, cultured human
      melanocytes were stimulated with calcitonin gene-related peptide (CGRP),
      substance P, or vasoactive intestinal peptide, neuropeptides known to be present
      in cutaneous nerves, to examine their possible functions in the epidermal melanin
      unit. CGRP increased DNA synthesis rate of melanocytes in a concentration- and
      time-dependent manner. Cell yields after 5 d were increased 25% compared with
      controls maintained in an otherwise optimized medium. Furthermore, stimulation by
      CGRP induced rapid and dose-dependent accumulation of intracellular cAMP,
      suggesting that the mitogenic effect is mediated by the cAMP pathway. These
      studies confirm and expand a single earlier report in an animal model of physical
      contact between melanocytes and cutaneous nerves and for the first time strongly
      suggest that the nervous system may exert a tonic effect on melanocytes in normal
      or diseased human skin.

PMID- 8879212
TI  - Immune and inflammatory responses in TNF alpha-deficient mice: a critical
      requirement for TNF alpha in the formation of primary B cell follicles,
      follicular dendritic cell networks and germinal centers, and in the maturation of
      the humoral immune response.
AB  - To investigate the role of TNF alpha in the development of in vivo immune
      response we have generated TNF alpha-deficient mice by gene targeting. Homozygous
      mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and
      show no apparent phenotypic abnormalities, indicating that TNF alpha is not
      required for normal mouse development. In the absence of TNF alpha mice readily
      succumb to L. monocytogenes infections and show reduced contact hypersensitivity
      responses. Furthermore, TNF alpha knockout mice are resistant to the systemic
      toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to
      high doses of LPS alone. Most interestingly, TNF alpha knockout mice completely
      lack splenic primary B cell follicles and cannot form organized follicular
      dendritic cell (FDC) networks and germinal centers. However, despite the absence
      of B cell follicles, Ig class-switching can still occur, yet deregulated humoral
      immune responses against either thymus-dependent (TD) or thymus-independent (TI)
      antigens are observed. Complementation of TNF alpha functioning by the expression
      of either human or murine TNF alpha transgenes is sufficient to reconstitute
      these defects, establishing a physiological role for TNF alpha in regulating the
      development and organization of splenic follicular architecture and in the
      maturation of the humoral immune response.

PMID- 8879213
TI  - Regulation of dendritic cell numbers and maturation by lipopolysaccharide in
      vivo.
AB  - Dendritic cells (DC) are described as "nature's adjuvant," since they have the
      capacity to sensitize T cells in vivo upon first encounter with the antigen. The
      potent accessory properties of DC appear to develop sequentially. In particular,
      the ability to process antigens and to sensitize native T cells develops in
      sequence, a process termed "maturation" that is well described in vitro. Here, we
      obtain evidence for maturation in vivo in response to the bacterial product
      lipopolysaccharide (LPS). Before LPS treatment, many DC are found at the margin
      between the red and white pulp. These cells lack the M342 and DEC-205 markers,
      but process soluble proteins effectively. 6 h after LPS, DC with the M342 and DEC
      205 markers are found in increased numbers in the T cell areas. These cells have
      a reduced capacity to process proteins, but show increases in the B7 costimulator
      and T cell stimulatory capacity. 48 h after LPS, the number of DC in the spleen
      is reduced markedly. We interpret these findings to mean that LPS can cause DC in
      the marginal zone to mature and to migrate into and then out of the T cell areas.

PMID- 8879214
TI  - Inducible nitric oxide synthase in tangle-bearing neurons of patients with
      Alzheimer's disease.
AB  - In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein,
      components of which can induce mouse microglia to express the high-output isoform
      of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In
      mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta
      1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation
      that might be permissive for accumulation of NOS2. Accordingly, we investigated
      the expression of NOS2 in patients with AD, using three monospecific antibodies:
      a previously described polyclonal and two new monoclonal antibodies.
      Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in
      brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was
      undetectable in brains from 6 control subjects aged 23-72 years, but was
      expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human
      neurons can express NOS2 in vivo. The high-output pathway of NO production may
      contribute to pathogenesis in AD.

PMID- 8879215
TI  - Interferon gamma regulates platelet endothelial cell adhesion molecule 1
      expression and neutrophil infiltration into herpes simplex virus-infected mouse
      corneas.
AB  - In a mouse model of herpes simplex virus (HSV) 1 corneal infection, tissue
      destruction results from a CD4+ T cell-mediated chronic inflammation, in which
      interleukin 2 and interferon (IFN) gamma are requisite inflammatory mediators and
      polymorphonuclear leukocytes (PMN) are the predominant infiltrating cells. In
      vivo neutralization of IFN-gamma relieved inflammation at least in part through a
      specific block of PMN extravasation into HSV-1-infected corneas. Intercellular
      adhesion molecule (ICAM) 1 and platelet endothelial cell adhesion molecule
      (PECAM) 1 were upregulated on the vascular endothelium of inflamed corneas.
      Reduced PMN extravasation in anti-IFN-gamma-treated mice was associated with a
      dramatic reduction of PECAM-1 but not ICAM-1 expression on vascular endothelium.
      PMN accumulated in the lumen of corneal vessels after in vivo IFN-gamma
      neutralization. PECAM-1 was readily detectable on PMN inside the vessels but was
      not detectable on PMN that extravasated into the infected cornea. Moreover, flow
      cytometric analysis revealed reduced PECAM-1 expression but elevated major
      histocompatibility complex class I expression on PMN that recently extravasated
      into the peritoneal cavity when compared with PMN in the peripheral blood. We
      conclude that IFN-gamma contributes to HSV-1-induced corneal inflammation by
      facilitating PMN infiltration; this appears to be accomplished through
      upregulation of PECAM-1 expression on the vascular endothelium; and PMN
      downregulate PECAM-1 expression during the process of extravasation.

PMID- 8879216
TI  - Identification of novel lymphoid tissues in murine intestinal mucosa where
      clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop.
AB  - We have revealed that about one and a half thousand tiny clusters, filled with
      one thousand closely packed lymphocytes, can be found throughout the murine small
      and large intestinal mucosa. They are located in crypt lamina propria
      (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large
      fraction of lymphocytes in CP expresses c-kit, IL-7R, Thy1 and a lymphocyte
      function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR alpha
      beta-, TCR gamma delta-, sIgM-, and B220-. The population size of IL-2R alpha+,
      HSA+ and Pgp-1+ subsets is variable (20-50%) and the composition of CD8+, Ly-1+,
      and CD4+ subsets is smaller but also variable (3-20%). In the small intestine, CP
      do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but
      do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of
      DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower
      than that in the thymic cortex and is almost comparable with that in the thymic
      medulla. The numbers of CP remain the same in aged mice (> 114 wk) but double
      after estrogen treatment even though the thymi are attenuated sharply in both
      conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue
      level of cellular behavior, neither PP, isolated lymphoid follicles, peripheral
      LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina
      propria of IL-7R-deficient mice that display a profound reduction in thymic and
      peripheral lymphoid cellularity. By contrast, CP are present in germ-free mice
      and in athymic (nu/nu), SCID, TCR beta x delta-/-, RAG-2-/-, PP-deficient
      (aly/aly), stem cell factor (Sl/Sld) and c-kit (W/Wv) mutant mice. Taking all of
      these results together, CP are the first identification of gut-associated murine
      lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic
      progenitors for T and/or B cell descendants may start to take place at the age of
      commencement of weaning.

PMID- 8879217
TI  - T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophila.
AB  - T lymphocytes have been implicated in controlling the recruitment of eosinophils
      into the lung in murine models of allergic asthma. The mechanism by which T cells
      assist in the recruitment of eosinophils to the lung in these models is not
      completely understood. We hypothesized that eosinophil-active chemokines might be
      regulated by antigen (Ag)-induced T cell activation in vivo and thereby mediate T
      cell-dependent eosinophil recruitment. To test this hypothesis, we examined the
      effect of an anti-CD3 mAb on Ag-induced pulmonary eosinophilia and correlated
      this with the expression of three eosinophil-active chemokines: eotaxin,
      macrophage inflammatory protein (MIP)-1 alpha, and RANTES. We found that Ag
      induced pulmonary eosinophilia was associated with the induction of eotaxin and
      MIP-1 alpha, but not RANTES mRNA. Prechallenge treatment with anti-CD3 mAb
      inhibited eotaxin, but not MIP-1 alpha and RANTES mRNA induction, and
      significantly reduced eosinophil accumulation in the lung. In addition, Ag
      specific antibody responses and mast cell degranulation after Ag challenge in
      sensitized mice were not affected by T cell elimination, and were not sufficient
      to induce the expression of eotaxin and cause pulmonary eosinophilia. These
      findings suggest that eotaxin is one of the molecular links between Ag-specific T
      cell activation and the recruitment of eosinophils into the airways.

PMID- 8879218
TI  - TCR binding differs for a bacterial superantigen (SEE) and a viral superantigen
      (Mtv-9).
AB  - Both superantigens (SAG) and many anti-TCR monoclonal antibodies (mAb) have
      specificity for the V beta region of the TCR encoded by TCRBV genes. For instance
      the bacterial SAG staphylococcal enterotoxin E (SEE), the retroviral SAG MTV-9
      and the mAb OT145 each react with human T cells expressing BV6S7. This BV gene
      encodes two common alleles. We found that SEE and the mAb preferentially activate
      T cells expressing BV6S7*1 as opposed to BV6S7*2, but Mtv-9 activates T cells
      expressing either allele. Thus binding to the TCR differs between the two SAGs. A
      mutation in the TCR HVR-4 region of BV6S7*1 (G72E), where the two BV6S7 alleles
      differ, indicated that HVR-4 is a component of the binding site for SEE and for
      the mAb OT145. BV6S7*2 has a charged E72 which may result in electrostatic
      repulsion of SEE, as SEE contains a similarly acidic aspartic acid residue at a
      TCR interaction site (204D).

PMID- 8879219
TI  - The importance of leukotrienes in airway inflammation in a mouse model of asthma.
AB  - Inhalation of antigen in immunized mice induces an infiltration of eosinophils
      into the airways and increased bronchial hyperreactivity as are observed in human
      asthma. We employed a model of late-phase allergic pulmonary inflammation in mice
      to address the role of leukotrienes (LT) in mediating airway eosinophilia and
      hyperreactivity to methacholine. Allergen intranasal challenge in OVA-sensitized
      mice induced LTB4 and LTC4 release into the airspace, widespread mucus occlusion
      of the airways, leukocytic infiltration of the airway tissue and broncho-alveolar
      lavage fluid that was predominantly eosinophils, and bronchial hyperreactivity to
      methacholine. Specific inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating
      protein (FLAP) blocked airway mucus release and infiltration by eosinophils
      indicating a key role for leukotrienes in these features of allergic pulmonary
      inflammation. The role of leukotrienes or eosinophils in mediating airway
      hyperresponsiveness to aeroallergen could not be established, however, in this
      murine model.

PMID- 8879220
TI  - Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of
      a dominant tumor clone derived from (crippled) germinal center B cells.
AB  - In Hodgkin's disease (HD), the Hodgkin and Reed-Sternberg (HRS) cells represent
      only a minute population in the diseased tissue. The investigation of lineage
      derivation and clonal origin of these cells has yielded conflicting results. We
      have analyzed HRS cells micromanipulated from infiltrated tissue sections of 10
      primary HD patients for rearranged V genes, extending a previous study. Clonally
      related rearrangements were found in nine cases, indicating that HRS cells
      represent a dominant clone of B lineage-derived cells in at least a large
      fraction of cases of HD. Rearranged VH genes from HRS cells carried a high load
      of somatic mutation, indicating that HRS cells are derived from germinal center
      (GC) cells or their progeny. Stop codons in some in-frame V gene rearrangements
      suggest that the HRS cell precursors reside inside GCs, have acquired crippling
      mutations that prevent antigenic selection, but escape apoptosis through some
      transforming event.

PMID- 8879221
TI  - Beta 2-microglobulin-dependent T cells are dispensable for allergen-induced T
      helper 2 responses.
AB  - CD4+ and CD8+ alpha/beta+ T cells of the T helper cell (Th)2 phenotype produce
      the cytokines IL-4, IL-5, and IL-13 that promote IgE production and eosinophilic
      inflammation. IL-4 may play an important role in mediating the differentiation of
      antigenically naive alpha/beta+ T cells into Th2 cells. Murine NK1.1+ (CD4+ or
      CD4-CD8-) alpha/beta+ T cells comprise a beta 2-microglobulin (beta 2m)-dependent
      cell population that rapidly produces IL-4 after cell activation in vitro and in
      vivo and has been proposed as a source of IL-4 for Th2 cell differentiation.
      alpha/beta+ CD8+ T cells, most of which require beta 2m for their development,
      have also been proposed as positive regulators of allergen-induced Th2 responses.
      We tested whether beta 2m-dependent T cells were essential for Th2 cell-mediated
      allergic reactions by treating wild-type, beta 2m-deficient (beta 2m -/-), and IL
      4-deficient (IL-4 -/-) mice of the C57BL/6 genetic background with ovalbumin
      (OVA), using a protocol that induces robust allergic pulmonary disease in wild
      type mice. OVA-treated beta 2m -/- mice had circulating levels of total and OVA
      specific IgE, pulmonary eosinophilia, and expression of IL-4, IL-5, and IL-13
      mRNA in bronchial lymph node tissue similar to that of OVA-treated wild-type
      mice. In contrast, these responses in OVA-treated IL-4 -/- mice were all either
      undetectable or markedly reduced compared with wild-type mice, confirming that IL
      4 was required in this allergic model. These results indicate that the NK1.1+
      alpha/beta+ T cell population, as well as other beta 2m-dependent populations,
      such as most peripheral alpha/beta+ CD8+ T cells, are dispensable for the Th2
      pulmonary response to protein allergens.

PMID- 8879222
TI  - Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis
      brain.
AB  - Immunohistochemical methods were used to search for Fas receptor/Fas ligand
      system involvement in multiple sclerosis (MS) white matter brain lesions. We
      found large numbers of Fas ligand (Fas-L)-bearing cells present in two acute
      lesions and 12 of 16 chronic MS lesions, and very few positive cells in non
      inflammatory controls. Four of six brains from non-MS neuropathologic conditions
      associated with inflammation and white matter disease were, however, also
      positive for Fas-L. Double staining with cell-specific markers revealed that the
      pattern of ligand-positive cells in chronic MS lesions was complex and composed
      of several different cell types which were primarily resident glial cells with a
      small overlay of macrophages. Fas/APO 1 (CD95) receptor expression in MS tissue
      was also evaluated and marked upregulation of the receptor was found. In
      addition, Fas receptor was induced, but to a lesser extent, in numerous control
      brains. The observations that TUNEL-positive dying cells were present in MS
      lesions and showed excellent co-localization with Fas-L, indicate that the Fas
      death system may contribute to plaque pathogenesis and could lead to the
      development of a new category of therapeutic agents for MS.

PMID- 8879223
TI  - Production of nitric oxide in the synovial membrane of rheumatoid and
      osteoarthritis patients.
AB  - We have demonstrated spontaneous nitric oxide (NO) production by primary synovial
      cultures from rheumatoid (RA) and osteoarthritis patients. Increased NO
      production followed addition of staphylococcal enterotoxin B. Immunochemical
      double staining with specific anti-human inducible NO synthase (iNOS) and
      nonspecific esterase (NSE), or anti-CD68 (markers for tissue macrophages) showed
      that although many lining layer cells in RA synovium expressed iNOS, most
      (approximately 90%) were NSE- and CD68-, with only a minor population
      (approximately 10%) which were iNOS+, CD68+/NSE+. These data demonstrate the
      capacity for high output of NO by human synovial tissue and show that, although
      human macrophages can express high levels of iNOS, the majority of cells
      expressing iNOS are fibroblasts. We also report that synoviocytes, and macrophage
      cell lines, cultured with the NO donor, S-nitroso-acetyl penicillamine, produced
      high concentrations of tumor necrosis factor (TNF)-alpha. These results suggest
      that NO may mediate pathology in RA through the induction of TNF-alpha
      production.

PMID- 8879224
TI  - Selective activation of the calcium signaling pathway by altered peptide ligands.
AB  - We previously demonstrated that altered peptide ligands (APL) can partially
      activate T cells, resulting in multiple distinct functional phenotypes, including
      the induction of anergy. Such APL stimulate a unique pattern of T cell receptor
      (TCR) phospho-zeta species, and lack associated ZAP-70 kinase activity. While
      these data suggested that selective signaling pathways downstream of the TCR/CD3
      molecules are activated upon APL stimulation, they did not directly demonstrate
      this. Thus, we pursued intracellular signaling events successfully stimulated by
      APL. Because our previous studies showed that cyclosporin A (CsA) completely
      inhibited anergy induction, we assessed whether TCR ligation by APL cause a rise
      in cytosolic calcium (Ca+2). Our results show that these ligands can induce Ca+2
      transients, in contrast to data generated using analogue peptides in other
      antigen systems. These opposing results may reflect differences in the
      intracellular signaling pathways utilized by different APL, or may be due to the
      exquisite sensitivity of the assay used here. Importantly, the APL-stimulated
      Ca+2 induction is both initiated and sustained at lower levels than that
      stimulated by a strong agonist signal, but resembles that stimulated by a weaker
      agonist stimulus. Alone, the less than optimal Ca+2 induction does not cause
      anergy, because ionomycin treatment together with the APL does not result in a
      proliferative signal. Instead, we propose that a combination of this and other
      signaling pathways induces T cell anergy. Overall, these data support the concept
      of differential signaling in T cells, as a direct consequence of the
      phosphotyrosine status of the TCR/CD3 molecules.

PMID- 8879225
TI  - The domain on the Duffy blood group antigen for binding Plasmodium vivax and P.
      knowlesi malarial parasites to erythrocytes.
AB  - Plasmodium vivax and the related simian malarial parasite P. knowlesi use the
      Duffy blood group antigen as a receptor to invade human erythrocytes and region
      II of the parasite ligands for binding to this erythrocyte receptor. Here, we
      identify the peptide within the Duffy blood group antigen of human and rhesus
      erythrocytes to which the P. vivax and P. knowlesi ligands bind. Peptides from
      the NH2-terminal extracellular region of the Duffy antigen were tested for their
      ability to block the binding of erythrocytes to transfected Cos cells expressing
      on their surface region II of the Duffy-binding ligands. The binding site on the
      human Duffy antigen used by both the P. vivax and P. knowlesi ligands maps to a
      35-amino acid region. A 34-amino acid peptide from the equivalent region of the
      rhesus Duffy antigen blocked the binding of P. vivax to human erythrocytes,
      although the P. vivax ligand expressed on Cos cells does not bind rhesus
      erythrocytes. The binding of the rhesus peptide, but not the rhesus erythrocyte,
      to the P. vivax ligand was explained by interference of carbohydrate with the
      binding process. Rhesus erythrocytes, treated with N-glycanase, bound
      specifically to P. vivax region II. Thus, the interaction of P. vivax ligand with
      human and rhesus erythrocytes appears to be mediated by a peptide-peptide
      interaction. Glycosylation of the rhesus Duffy antigen appears to block binding
      of the P. vivax ligand to rhesus erythrocytes.

PMID- 8879226
TI  - B cells lacking RelB are defective in proliferative responses, but undergo normal
      B cell maturation to Ig secretion and Ig class switching.
AB  - A number of distinct functional abnormalities have been observed in B cells
      derived from p50/ NF-kappa B or c-rel knockout mice. RelB, another member of the
      NF-kappa B/Rel family of transcription factors, is expressed during the latter
      stages of B cell maturation and can bind to regulatory sites within the Ig heavy
      chain locus. Therefore, we tested the ability of B cells from relB knockout mice
      (relB-/-) to proliferate, undergo maturation to IgM secretion, and switch to the
      expression of downstream Ig isotypes in response to distinct activators including
      LPS, anti-CD40 mAb or CD40 ligand, and/or dextran anti-IgD antibodies in
      combination with various cytokines, including IL-4, IL-5, IFN-gamma, and TGF
      beta. B cells lacking RelB showed up to 4-fold reductions in DNA synthesis in
      response to LPS, CD40, and membrane Ig-dependent activation relative to controls.
      However, relB-/- B cells were comparable to control B cells in their ability to
      undergo maturation to IgM secretion and switch to the expression of IgG3, IgG1,
      IgG2b, IgG2a, IgE, and/or IgA under all activation conditions tested. Thus, RelB,
      like c-Rel and p50/NF-kappa B, plays a role in B cell proliferation. However, in
      contrast to c-Rel and p50/ NF-kappa B, it is not critically involved in
      maturation to Ig secretion or expression of Ig isotypes.

PMID- 8879227
TI  - Perforin and Fas killing by CD8+ T cells limits their cytokine synthesis and
      proliferation.
AB  - During an immune response, effector CD8+ T cells can kill infected cells by the
      perforin-dependent pathway. In comparison to CD4+ T cells, which are major
      sources of cytokines, normal CD8+ T cells produced less interleukin 2 and
      interferon gamma, and proliferated less vigorously after antigenic stimulation.
      Killing of target cells was a major cause of these reduced responses, since
      perforin-deficient CD8+ T cells showed substantially increased cytokine synthesis
      and proliferation. Cytotoxicity by the alternate Fas pathway also resulted in
      self-limitation of CD8+ T cell cytokine synthesis. This relationship between
      cytotoxicity and cytokine synthesis may regulate CD8+ T function in different
      phases of an immune response.

PMID- 8879228
TI  - Proteolytic processing activates a viral superantigen.
AB  - Mouse mammary tumor virus (MMTV) superantigens (vSAg) undergo proteolytic
      processing at residues that have been demonstrated in vitro to be recognition
      sites for the endoprotease furin. To examine the role of furin in the
      presentation of vSAg7 to T cells, the vSAg7 and class II MHC IEk genes were
      introduced into Chinese Hamster Ovary (CHO) cells (furin-positive) and into a
      furin-negative CHO variant (FD11). Both transfected cell lines efficiently
      presented peptide antigen and bacterial superantigens to T cell hybridomas.
      However, while the furin-positive cells presented vSAg7 well, the furin-negative
      cells presented poorly. Transient transfection of the furin-negative cells with
      an expression plasmid containing the furin gene restored the ability to present
      vSAg7 efficiently. The marginal presentation of vSAg7 observed using the furin
      negative transfectants was eliminated after culture with the protease inhibitor
      leupeptin, suggesting that one or more endoproteases other than furin have a
      detectable but limited capacity to proteolytically activate vSAg7. Biochemical
      analyses revealed that vSAg7 was largely unprocessed in the absence of furin.
      Thus, viral superantigens, unlike bacterial superantigens, require proteolytic
      processing to activate T cells.

PMID- 8879229
TI  - Gene vaccination with naked plasmid DNA: mechanism of CTL priming.
AB  - The injection of naked plasmid DNA directly into the muscle cells of mice has
      been shown to induce potent humoral and cellular immune responses. The generation
      of a cytotoxic T lymphocyte (CTL) response after plasmid DNA injection may
      involve the presentation of the expressed antigen in the context of the injected
      myocytes' endogenous major histocompatibility (MHC)-encoded class I molecules or
      may use the MHC molecules of bone marrow-derived antigen presenting cells (APC)
      which are capable of providing co-stimulation as well. To resolve which cell type
      provides the specific restricting element for this method of vaccination we
      generated parent-->F1 bone marrow chimeras in which H-2bxd recipient mice
      received bone marrow that expressed only H-2b or H-2d MHC molecules. These mice
      were injected intramuscularly with naked plasmid DNA that encoded the
      nucleoprotein from the A/PR/8/34 influenza strain, which as a single antigen has
      epitopes for both H-2Db and H-2Kd. The resulting CTL responses were restricted to
      the MHC haplotype of the bone marrow alone and not to the second haplotype
      expressed by the recipient's myocytes. The role of somatic tissues that express
      protein from injected plasmids may be to serve as a reservoir for that antigen
      which is then transferred to the APC. Consequently, our data show that the
      mechanism of priming in this novel method for vaccination uses the MHC from bone
      marrow-derived APC, which are efficient at providing all of the necessary signals
      for priming the T cell.

PMID- 8879230
TI  - Inactivation of the IL-6 gene prevents development of multicentric Castleman's
      disease in C/EBP beta-deficient mice.
AB  - Castleman's disease is a lymphoproliferative disorder thought to be related to
      deregulated production of IL-6. We have previously shown that mice lacking the
      trans-acting factor C/EBP beta, a transcriptional regulator of IL-6 and a
      mediator of IL-6 intracellular signaling, develop a pathology nearly identical to
      multicentric Castleman's disease, together with increasingly high levels of
      circulating IL-6. We describe here how the simultaneous inactivation of both IL-6
      and C/EBP beta genes prevents the development of pathological traits of
      Castleman's disease observed in C/EBP beta-deficient mice. Histological and
      phenotypic analysis of lymph nodes and spleen of double mutant mice did not show
      either the lymphoadenopathy and splenomegaly or the abnormal expansion of
      myeloid, B and plasma cell compartments observed in C/EBP beta-/- mice, while B
      cell development, although delayed, was normal. Our data demonstrate that IL-6 is
      essential for the development of multicentric Castleman's disease in C/EBP beta-/
      mice.

PMID- 8879231
TI  - Neutrophil activation by anti-proteinase 3 antibodies in Wegener's
      granulomatosis: role of exogenous arachidonic acid and leukotriene B4 generation.
AB  - Among the anti-neutrophil cytoplasmic antibodies (ANCA), those targeting
      proteinase 3 (PR3) have a high specificity for Wegener's granulomatosis (WG). It
      is known that a preceding priming of neutrophils with cytokines is a prerequisite
      for membrane surface expression of PR3, which is then accessible to autoantibody
      binding. Employing a monoclonal antibody directed against human PR3 and ANCA
      positive serum from WG patients with specificity for PR3, we now investigated the
      role of free arachidonic acid (AA) in autoantibody-related human neutrophil
      activation. Priming of neutrophils with tumor necrosis factor (TNF-alpha) for 15
      min or exposure to anti-PR3 antibodies or incubation with free AA (10 microM) as
      sole events did not provoke superoxide generation, elastase secretion or
      generation of 5-lipoxygenase products of AA. Similarly, the combination of TNF
      alpha-priming and AA incubation was ineffective. When TNF-alpha-primed
      neutrophils were stimulated by anti-PR3 antibodies, superoxide and elastase
      secretion was provoked in the absence of lipid mediator generation. However, when
      free AA was additionally provided, a strong activation of the 5-lipoxygenase
      pathway was demasked, with the appearance of excessive quantities of leukotriene
      (LT)B4, LTA4, and 5-hydroxyeicosatetraenoic acid. Moreover, superoxide and
      elastase secretion were markedly amplified, and studies with 5-lipoxygenase
      inhibitors and a LTB4-antagonist demonstrated this was due to an LTB4-related
      autocrine loop of cell activation. In contrast, the increased synthesis of
      platelet-activating factor in response to TNF-alpha-priming and anti-PR3
      stimulation did not contribute to the amplification loop of neutrophil activation
      under the given conditions. We conclude that anti-PR3 antibodies are potent
      inductors of the 5-lipoxygenase pathway in primed human neutrophils, and
      extracellular free AA, as provided at an inflammatory focus, synergizes with the
      autoantibodies to evoke full-blown lipid mediator generation, granule secretion
      and respiratory burst. Such events may be enrolled in the pathogenesis of focal
      necrotizing vascular injury in Wegener's granulomatosis.

PMID- 8879232
TI  - Self major histocompatibility complex class I antigens expressed solely in
      lymphoid cells do not induce tolerance in the CD4+ T cell compartment.
AB  - Transgenic mice expressing self major histocompatibility complex (MHC) class I (H
      2Kb) antigen solely in lymphoid cell lineages do not acquire tolerance to H-2Kb
      expressed on skin grafts. H-2Kb-specific cytotoxic T cell responses were
      completely abrogated in these mice, even after they had rejected skin grafts.
      Moreover, thymocytes expressing T cell receptors that confer H-2Kb reactivity on
      cytotoxic CD8+ T cells were eliminated. The ability to reject grafts correlated
      with the presence of a novel population of H-2Kb-reactive CD4+ T cells. At least
      some of these CD4+ T cells recognize peptides derived from H-2Kb by processing.
      We conclude that self MHC I antigens induce tolerance in the CD8 T cell
      compartment via negative selection when expressed exclusively by lymphoid cells.
      In contrast, tolerance to MHC class II-restricted self peptides derived by
      processing of such MHC I antigens is not induced in the CD4 T cell compartment.
      This suggests that effective transfer of self antigens from lymphoid cells to MHC
      II-positive cells that can process and present them as self peptides to
      thymocytes or CD4+ T cells does not take place in vivo. Thus, sequestration of
      self antigens and MHC II molecules in distinct cell types in the thymic
      microenvironment allows potentially autoreactive and functionally competent CD4+
      T cells that recognize cryptic MHC II-restricted self peptides to mature into the
      peripheral T cell repertoire under normal physiological circumstances.

PMID- 8879233
TI  - Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in
      transporters associated with antigen presentation-1 null and thymus leukemia
      antigen positive mice.
AB  - Thymic selection of natural killer-1+ natural T cells that express alpha beta T
      cell receptors requires a conserved beta 2-microglobulin-associated molecule,
      presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that
      positive selection of natural T cells occurs independent of transporters
      associated with antigen presentation-1 (TAP-1) function. Moreover, natural T
      cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules
      function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o
      thymocytes, they could play a role in natural T cell development. Of these class
      Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that
      thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically
      expanded natural T cell repertoire compared with TL- mice. This expansion, as in
      TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains
      expressed by natural T cells, suggesting that TL and CD1d impact similar
      repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell
      development.

PMID- 8879234
TI  - A p70 killer cell inhibitory receptor specific for several HLA-B allotypes
      discriminates among peptides bound to HLA-B*2705.
AB  - Natural killer (NK) cells express a repertoire of killer cell inhibitory
      receptors (KIR) for major histocompatibility complex (MHC) class I molecules. KIR
      specificity for MHC class I can be broad, as in the case of a single p70 KIR that
      can recognize several HLA-B allotypes, including HLA-B*2705. On the other hand,
      recognition of MHC class I can also be highly specific, as in the case of NK
      clones that recognize HLA-B*2705 in a peptide-specific manner. Most NK cells
      express multiple KIR sequences. To determine whether the broad and specific types
      of HLA-B recognition by NK cells reflect the use of different receptors or a
      property of a single KIR we analyzed the recognition of HLA-B*2705 by the p70 KIR
      11, known to recognize several HLA-B allotypes. Vaccinia virus-mediated
      expression of KIR-11 in NK clones resulted in inhibition by HLA-B*2705 molecules
      on wild type but not on target cells deficient in the transporter for antigen
      presentation (TAP). Two peptides (FRYNGLIHR and RRSKEITVR) loaded onto HLA-B*2705
      molecules on TAP-deficient cells provided protection from lysis by NK cells
      expressing KIR-11 but three other B27-specific peptides did not. As the five
      peptides bound to HLA-B*2705 with similar stability, these data demonstrate that
      a single KIR specific for several HLA-B allotypes recognizes a subset of peptides
      bound to HLA-B*2705.

PMID- 8879235
TI  - Mild RIP-an alternative method for in vivo mutagenesis of the albino-3 gene in
      Neurospora crassa.
AB  - We have used a biological phenomenon that occurs in Neurospora crassa, termed
      Repeat-Induced Point mutation (RIP), to create partially functional mutant
      alleles of the albino-3 (al-3) gene encoding geranylgeranyl pyrophosphate
      synthase, an enzyme involved in the biosynthesis of carotenoids and diverse
      prenylated compounds. A total of 70 RIP-induced al-3 mutants were identified by
      their pale albino phenotype, resulting from inactivation of carotenoid bio
      synthesis. Nucleotide sequence analysis of the al-3 gene in five of the RIP
      induced mutants revealed that in each case RIP had introduced no more than six
      point mutations. The low frequency of RIP mutants (0.42%) and the isolation of
      only leaky mutants with very few mutations suggest that ascospores containing a
      heavily mutated al-3 gene do not survive. These results are evidence that the RIP
      phenomenon, used to inactivate and silence duplicated genes in N. crassa, may be
      exploited in its mild version as a method of sequence-specific in vivo
      mutagenesis to obtain functional mutant alleles of Neurospora genes. This mild
      form of mutagenesis may be particularly advantageous in selecting for leaky
      mutations in essential Neurospora genes.

PMID- 8879236
TI  - Altered expression of nuclear genes encoding chloroplast polypeptides in non
      photosynthetic mutants of Chlamydomonas reinhardtii: evidence for post
      transcriptional regulation.
AB  - In photoautotrophic organisms it is well documented that the expression of
      nuclear genes encoding plastid proteins can be regulated at various levels. We
      present here the analysis of a non-photosynthetic strain (CC1051) of the green
      unicellular alga Chlamydomonas reinhardtii; this strain carries a mutation in the
      newly identified Cen gene involved in the co-regulated expression of several
      different nuclear genes encoding plastid proteins. We performed a differential
      screening strategy to isolate cDNAs corresponding to genes that are
      differentially expressed in mutant and wild-type strains. Extensive hybridization
      experiments revealed that the 15 cDNA clones isolated represent five different
      mRNAs that fail to accumulate in the non-photosynthetic mutant. Comparative
      analysis of DNA sequencing data showed that they all code for plastid proteins.
      In particular, we identified genes for the chlorophyll a/b binding protein of the
      light-harvesting complex II (LHCII), for subunits II and III of photosystem I
      (PsaD, PsaF), for pentose-5-phosphate 3-epimerase (PPE), an enzyme of the Calvin
      cycle, and for an unidentified 7 kDa protein with a suggested lumenal location.
      With the exception of the gene for LHCII, all proteins are encoded by single-copy
      genes. Evidence from run-on transcription experiments is presented showing that
      expression of the above mentioned plastid proteins is affected at the post
      transcriptional level in the mutant strain CC1051 with a defect in the Cen gene.
      Our results suggest that the product of the Cen gene is involved in stabilization
      and/or processing of transcripts from nuclear genes encoding chloroplast
      proteins.

PMID- 8879237
TI  - A chloroplast-derived sequence is utilized as a source of promoter sequences for
      the gene for subunit 9 of NADH dehydrogenase (nad9) in rice mitochondria.
AB  - The chloroplast-derived sequence trnS-rps4/ 3'trnL-trnF-ndhJ-ndhK (4066 bases in
      length) is present in a region that starts 355 bases upstream of the gene for
      subunit 9 of NADH dehydrogenase (nad9) in the mitochondrial genome of rice.
      Northern blot hybridization revealed that three large transcripts of 3.05, 1.62
      and 1.05 kb hybridized to strand-specific probes for both the nad9 gene and the
      chloroplast-derived sequence, indicating that the nad9 gene was transcribed
      together with the chloroplast-derived sequence. From the results of in vitro
      capping and ribonuclease protection experiments, as well as primer extension
      analysis, we identified at least seven sites for the initiation of transcription
      of nad9 in the chloroplast-derived sequence. All of the initiation sites for
      transcription of the nad9 gene were located in sequences homologous to
      chloroplast DNA. Two of seven initiation sites were flanked by a sequence
      homologous to the consensus promoter motif that includes the CRTA motif (where R
      is A or G) of the rice mitochondrion. However, the sequences surrounding the
      other five sites showed only limited similarity to the conserved sequence. It is
      suggested that all the promoters of the rice nad9 gene exist in a sequence that
      was transferred from the chloroplast during evolution. Thus, the chloroplast
      derived sequence has a novel, significant function in the mitochondrial genome of
      this higher plant.

PMID- 8879238
TI  - Development of gene transfer methods for Rubrivivax gelatinosus S1: construction,
      characterization and complementation of a puf operon deletion strain.
AB  - Gene transfer systems were developed in Rubrivivax (Rx.) gelatinosus S1. First, a
      system for conjugative transfer of mobilizable plasmids from Escherichia coli to
      Rx. gelatinosus S1 was established. Secondly, optimal conditions for the
      transformation of Rx. gelatinosus S1 by electroporation were determined. A delta
      puf strain was constructed. Complementation with the puf operon from a wild-type
      strain cloned in a replicative plasmid restored photosynthetic growth. Two
      insertion strains were also selected. All the strains constructed were green, due
      to a change in carotenoid content. Characterization of these strains provides
      genetic evidence for a "superoperon" organization in this bacterium.

PMID- 8879240
TI  - Transcription-induced deletions in plasmid vectors: M13 DNA replication as a
      source of instability.
AB  - We have previously shown that concurrent progression of pBR322 replication and
      pTac-directed transcription in opposite orientations induces illegitimate
      recombination events. We tested here the effects of M13 rolling circle
      replication on the incidence of plasmid deletions. The progression of the M13
      replication fork leads to an increase of more than 300-fold in the frequency of
      transcription-dependent deletion events. pBR322 derivatives carrying the M13
      replication origin and a 511 bp transcribed region under the control of the pTac
      promoter were used. Up to 12% of the plasmid population has sustained deletions
      within 4 h following the induction of pTac-directed transcription and M13 DNA
      replication, provided that the two proceed in opposite orientations. We observed
      that induction of transcription of the whole Escherichia coli lacZ gene (3244 bp)
      in the direction opposite to M13 replication leads to a fivefold decrease in
      plasmid copy number within 2 h, which is consistent with the proposal that
      deletions arise because replication fork progression is impeded. This decrease in
      parental plasmid copy number leads in turn to an enrichment in deleted plasmid
      forms. Our data confirm and extend the notion that simultaneous transcription and
      replication in opposite directions can efficiently promote deletion formation. In
      addition, this instability may be amplified when the rearranged molecules acquire
      a replicative advantage.

PMID- 8879239
TI  - Molecular and functional characterization of Slide, an Ac-like autonomous
      transposable element from tobacco.
AB  - A new transposable element of tobacco, Slide, was isolated from the tl mutant
      line, which shows somatic instability, after its transposition into a locus
      encoding nitrate reductase (NR). The Slide-124 element is 3733 bp long and its
      coding sequences show similarities with conserved domains of the transposases of
      Ac, Tam3 and hobo. Excision from the NR locus is detectable in somatic leaf
      tissues and Slide mobility is triggered by in vitro tissue culture. Slide
      excision events create footprints similar to those left by Ac and Tam3. Tobacco
      lines derived from the tl mutant line seem characterized by unmethylated copies
      of a few members of the highly repetitive Slide family. Slide mobility was
      monitored in transient expression assays. In wild-type tobacco protoplasts, the
      complete Slide element, as well as a defective copy, is able to excise. The
      complete Slide element, but not the defective version, is able to excise in
      protoplasts of the heterologous species lettuce (Lactuca sativa). These results
      show that Slide carries the functions required for its own mobility, and
      represents the first autonomous Ac-like element characterized in Solanaceae
      species.

PMID- 8879241
TI  - Striking differences in mitochondrial tRNA import between different plant
      species.
AB  - A systematic comparison of the tRNAs imported into the mitochondria of larch,
      maize and potato reveals considerable differences among the three species. Larch
      mitochondria import at least eleven different tRNAs (more than half of those
      tested) corresponding to ten different amino acids. For five of these tRNAs
      [tRNA(Phe(GAA)), tRNA(Lys(CUU)), tRNA(Pro(UGG)), tRNA(Ser(GCU)) and
      tRNA(Ser(UGA))] this is the first report of import into mitochondria in any plant
      species. There are also differences in import between relatively closely related
      plants; wheat mitochondria, unlike maize mitochondria import tRNA(His), and
      sunflower mitochondria, unlike mitochondria from other angiosperms tested, import
      tRNA(Ser(GCU)) and tRNA(Ser(UGA)). These results suggest that the ability to
      import each tRNA has been acquired independently at different times during the
      evolution of higher plants, and that there are few apparent restrictions on which
      tRNAs can or cannot be imported. The implications for the mechanisms of
      mitochondrial tRNA import in plants are discussed.

PMID- 8879242
TI  - TFIIS binds to mouse RNA polymerase I and stimulates transcript elongation and
      hydrolytic cleavage of nascent rRNA.
AB  - Efficient transcription elongation by RNA polymerase I (Pol I) requires a
      specific Pol I-associated factor, termed TIF-IC. Here we show that TFIIS, a
      factor that has previously been shown to promote read-through past many types of
      blocks to elongation by RNA polymerase II, also enhances Pol I-directed
      transcription elongation. In a reconstituted transcription system containing
      purified proteins, TFIIS stimulates Pol I transcription by increasing the overall
      rate of RNA chain elongation. As with Pol II, ternary Pol I complexes cleave the
      3' end of the nascent transcripts in response to TFIIS. The truncated RNAs remain
      bound to the template, are subject to pyrophosphorolysis, and can be chased into
      longer transcripts. Moreover, we show by immunoprecipitation and specific
      affinity chromatography that TFIIS physically interacts with Pol I. The results
      suggest that nascent transcript cleavage by TFIIS or a TFIIS-related factor may
      be a general mechanism by which both Pol I and Pol II can bypass transcriptional
      impediments.

PMID- 8879243
TI  - Yeast chitin synthases 1 and 2 consist of a non-homologous and dispensable N
      terminal region and of a homologous moiety essential for function.
AB  - Predicted protein sequences of fungal chitin synthases can be divided into a non
      homologous N-terminal region and a C-terminal region that shows significant
      homology among the various synthases. We have explored the function of these
      domains by constructing a series of nested deletions, extending from either end,
      in the CHS1 and CHS2 genes of Saccharomyces cerevisiae. In both cases, most or
      all of the sequences encoding the non-homologous N-terminal region (one-third of
      the protein for Chs1p and about one-fourth for Chs2p) could be excised, with
      little effect on the enzymatic activity in vitro of the corresponding synthase or
      on its function in vivo. However, further small deletions (20-25 amino acids)
      into the homologous region were deleterious to enzymatic activity and function,
      and often led to changes in the zymogenic character of the enzymes. Similarly,
      relatively small (about 75 amino acids) deletions from the C-terminus resulted in
      loss of enzymatic activity and function of both synthases. Thus, it appears that
      all the information necessary for membrane localization, enzymatic activity and
      function resides in the homologous regions of Chs1p and Chs2p, a situation that
      may also apply to other chitin synthases.

PMID- 8879244
TI  - Correlation of nonanucleotide motifs with transcript initiation of 18S rRNA genes
      in mitochondria of pea, potato and Arabidopsis.
AB  - Transcription initiation sites for the mitochondrial 18S rRNA genes in the dicot
      plants Arabidopsis thaliana, potato and pea were identified by a combination of
      in vitro capping, primer extension and S-1 analyses. These promoters contain a
      nonanucleotide motif and an AT-rich sequence similar to many mRNA and tRNA
      promoters in dicot mitochondria. In Arabidopsis and potato, active promoters are
      located within 120 nucleotides upstream of the 18S rRNA genes, as in Oenothera.
      The nucleotide sequence in the corresponding region in pea mitochondria is well
      conserved, but is not used as promoter in this plant. Instead a novel promoter
      sequence is used that lies several hundred nucleotides upstream. These results
      show that rRNAs can be transcribed from the same promoter types as mRNAs and
      tRNAs in plant mitochondria. However, the sequence features presently attributed
      to plant mitochondrial promoters-the conserved nonanucleotide and the upstream AT
      rich box-do not allow to deduce the presence of an active promoter from genomic
      sequence data alone.

PMID- 8879245
TI  - SOM 1, a small new gene required for mitochondrial inner membrane peptidase
      function in Saccharomyces cerevisiae.
AB  - IMP1 encodes a subunit of the mitochondrial inner membrane peptidase responsible
      for the proteolytic processing of cytochrome oxidase subunit 2 (Cox2) and
      cytochrome b2 (Cytb2). The molecular defect in an imp1 mutation and the
      characterisation of a high-copy-number suppressor is described. A deletion of the
      suppressor region causes respiration deficiency. The DNA sequence revealed three
      very small overlapping ORFs. Constructs which carried termination codons within
      the ORFs or lacked ATG initiation codons still retained complementing activity on
      a high-copy-number plasmid. Nevertheless, the possibility that the suppressor
      acts at DNA or RNA level could be excluded. Subcloning of the ORFs,
      complementation analysis in low-copy-number plasmids and transcript mapping
      identified the 222 bp ORF as the suppressor gene designated SOM1. The SOM1 gene
      is transcribed into a 375 bp polyadenylated RNA and the deduced amino acid
      sequence predicts a small protein of 8.4 kDa with no significant sequence
      similarity to known proteins. In the som1 deletion mutant, proteolytic processing
      of the Cox2 precursor is prevented and Cytb2 is strongly reduced. SOM1 represents
      a new small gene which encodes a novel factor that is essential for the correct
      function of the Imp1 peptidase and/or the protein sorting machinery.

PMID- 8879246
TI  - Respiration and low cAMP-dependent protein kinase activity are required for high
      level expression of the peroxisomal thiolase gene in Saccharomyces cerevisiae.
AB  - Transcription of genes for peroxisomal proteins is repressed by glucose and
      induced by oleate. At least for the peroxisomal thiolase gene (POT1) there is a
      third regulatory mechanism, mediated by the transcription factor Adr1p, which is
      responsible for the high-level expression of the gene in stationary phase. Here
      we show that a region in the POT1 promoter that extends from positions -238 to 
      152 mediates this mechanism, and we suggest that Adr1p acts indirectly on POT1.
      We have also analyzed the role of the cAMP-dependent protein kinase (PKA) in the
      transcriptional regulation of POT1. PKA exerts a negative control: the high,
      unregulated PKA activity in a bcy1 mutant maintains POT1 transcription at the
      repressed level. In a ras2 mutant, which has low PKA activity, glucose repression
      is not alleviated but in non-repressing conditions POT1 regulation is perturbed
      and expression prematurely increases during exponential phase. This suggests that
      the PKA signalling pathway controls the regulation of POT1 in stationary phase.
      Finally, we have found that Adr1p-dependent expression in stationary phase and
      induction by oleate are both abolished when respiration is blocked. Utilization
      of fatty acids as carbon source requires respiration. Our result points to the
      existence of mechanisms that co-ordinate the level of expression of thiolase and
      the functional state of the mitochondria.

PMID- 8879247
TI  - Mutants that show increased sensitivity to hydrogen peroxide reveal an important
      role for the pentose phosphate pathway in protection of yeast against oxidative
      stress.
AB  - We have isolated several mutants of Saccharomyces cerevisiae that are sensitive
      to oxidative stress in a screen for elevated sensitivity to hydrogen peroxide.
      Two of the sixteen complementation groups obtained correspond to structural genes
      encoding enzymes of the pentose phosphate pathway. Allelism of the pos10 mutation
      (POS for peroxide sensitivity) to the zwf1/met1 mutants in the structural gene
      for glucose 6-phosphate dehydrogenase was reported previously. The second
      mutation, pos18, was complemented by transformation with a yeast genomic library.
      The open reading frame of the isolated gene encodes 238 amino acids. No
      detectable ribulose 5-phosphate epimerase activity was found in the pos18 mutant,
      suggesting that the corresponding structural gene is affected in this mutant. For
      that reason the gene was renamed RPE1 (for ribulose 5-phosphate epimerase). RPE1
      was localized to chromosome X. The predicted protein has a molecular mass of
      25966 Daltons, a codon adaptation index (CAI) of 0.32, and an isoelectric point
      of 5.82. Database searches revealed 32 to 37% identity with ribulose 5-phosphate
      epimerases of Escherichia coli, Rhodospirillum rubrum, Alcaligenes eutrophus and
      Solanum tuberosum. We have characterized RPE1 by testing enzyme activities in
      rpe1 deletion mutants and in strains that overexpress RPE1, and compared the
      hydrogen peroxide sensitivity of rpe1 mutants to that of other mutants in the
      pentose phosphate pathway. Interestingly, all mutants tested (glucose 6-phosphate
      dehydrogenase, gluconate 6-phosphate dehydrogenase, ribulose 5-phosphate
      epimerase, transketolase, transaldolase) are sensitive to hydrogen peroxide.

PMID- 8879248
TI  - Comparable processing of beta-lactoglobulin pre-mRNA in cell culture and
      transgenic mouse models.
AB  - Eukaryotic pre-mRNAs undergo a variety of post-transcriptional modifications,
      including the removal of intronic sequences by splicing, leading to creation of a
      functional mRNA. We have compared the processing of transcripts generated from
      ovine beta-lactoglobulin gene constructs in stably transfected cells and in
      transgenic mice. In both the in vitro and in vivo model systems the removal of
      the middle two introns resulted in the inefficient splicing of the downstream,
      terminal intron. This intron-containing transcript was detected in the
      cytoplasmic RNA fraction. Thus, the initial in vitro analysis in cell lines of
      minigene constructs destined for expression in transgenic animals may provide a
      rapid and reliable indicator of the processing efficiency of the pre-mRNA
      produced by the construct in vivo. This is in contrast to the apparent
      limitations of in vitro systems in the analysis of transcription regulatory
      elements required for transgene expression.

PMID- 8879250
TI  - Characterization and application of soybean YACs to molecular cytogenetics.
AB  - Yeast artificial chromosomes (YACs) are widely used in the physical analysis of
      complex genomes. In addition to their value in chromosome walking for map-based
      cloning, YACs represent excellent probes for chromosome mapping using
      fluorescence in situ hybridization (FISH). We have screened such a library for
      low-copy-number clones by hybridization to total genomic DNA. Four clones were
      chosen for chromosome tagging based upon their low or moderate signal. By using
      degenerate oligonucleotide-primed PCR (DOP-PCR), we were able to use relatively
      small amounts of soybean YAC DNA, isolated directly by preparative pulsed-field
      gel electrophoresis, as FISH probes for both metaphase chromosome spreads and
      interphase nuclei. FISH chromosomal analysis using the three of the clones as
      probes resulted in relatively simple hybridization patterns consistent with a
      single homologous locus or two homoeologous loci. The fourth YAC probe resulted
      in a diffuse hybridization pattern with signal on all metaphase chromosomes. We
      conclude that YACs represent a valuable source of probes for chromosomal analysis
      in soybean.

PMID- 8879251
TI  - Asr genes belong to a gene family comprising at least three closely linked loci
      on chromosome 4 in tomato.
AB  - Asr1, Asr2 and Asr3 are three homologous clones isolated from tomato whose
      expression is believed to be regulated by abscisic acid (ABA); the corresponding
      genes thus participate in physiological and developmental processes such as
      responses of leaf and root to water stress, and fruit ripening. In this report,
      results obtained with Near Isogenic Lines reveal that Asr1, Asr2 and Asr3
      represent three different loci. In addition, we map these genes on the
      restriction fragment length polymorphism (RFLP) map of the tomato genome by using
      an F2 population derived from an interspecific hybrid cross L. esculentum x L.
      penelli. RFLP data allow us to map these genes on chromosome 4, suggesting that
      they belong to a gene family. The elucidation of the genomic organization of the
      Asr gene family may help in understanding the role of its members in the response
      to osmotic stress, as well as in fruit ripening, at the molecular level.

PMID- 8879249
TI  - Regulation of genes encoding subunits of the trehalose synthase complex in
      Saccharomyces cerevisiae: novel variations of STRE-mediated transcription
      control?
AB  - Saccharomyces cerevisiae cells show under suboptimal growth conditions a complex
      response that leads to the acquisition of tolerance to different types of
      environmental stress. This response is characterised by enhanced expression of a
      number of genes which contain so-called stress-responsive elements (STREs) in
      their promoters. In addition, the cells accumulate under suboptimal conditions
      the putative stress protectant trehalose. In this work, we have examined the
      expression of four genes encoding subunits of the trehalose synthase complex,
      GGS1/TPS1, TPS2, TPS3 and TSL1. We show that expression of these genes is
      coregulated under stress conditions. Like for many other genes containing STREs,
      expression of the trehalose synthase genes is also induced by heat and osmotic
      stress and by nutrient starvation, and negatively regulated by the Ras-cAMP
      pathway. However, during fermentative growth only TSL1 shows an expression
      pattern like that of the STRE-controlled genes CTT1 and SSA3, while expression of
      the three other trehalose synthase genes is only transiently down-regulated. This
      difference in expression might be related to the known requirement of trehalose
      biosynthesis for the control of yeast glycolysis and hence for fermentative
      growth. We conclude that the mere presence in the promoter of (an) active STRE(s)
      does not necessarily imply complete coregulation of expression. Additional
      mechanisms appear to fine tune the activity of STREs in order to adapt the
      expression of the downstream genes to specific requirements.

PMID- 8879252
TI  - Characterization of genes from Thermoanaerobacterium thermosulfurigenes EM1 that
      encode two glycosyl hydrolases with conserved S-layer-like domains.
AB  - Two genes from Thermoanaerobacterium thermosulfurigenes EM1 were identified which
      are predicted to encode a xylanase (XynA) and a polygalacturonate hydrolase
      (Pg1A). The xynA gene has the potential to encode a 1234-amino acid product
      consisting of a signal peptide followed by a repeated domain, a xylanase family F
      domain, two cellulose-binding domains and a triplicated sequence at its C
      terminus. The gene pglA is predicted to encode a product of 1148 amino acids
      consisting of a signal sequence followed by a fibronectin type III-like domain
      (Fn3 domain), the catalytic domain, a Gly/Thr/Ser/Asn-rich segment and a
      triplicated domain. The triplicated segments at the C-termini of deduced XynA and
      Pg1A are about 95% identical to each other and to the S-layer-like domains of the
      previously characterized pullulanase (AmyB) from the same organism. In contrast,
      sequence comparisons revealed only distant amino acid sequence similarities
      between the fibronectin type III-like domains of Pg1A and AmyB from T.
      thermosulfurigenes EM1.

PMID- 8879253
TI  - The importance of distinguishing "clinical judgement" in cancer management from
      "selection bias" in clinical trials.

PMID- 8879255
TI  - Frequent loss in chromosome 8p loci in liver cirrhosis accompanying
      hepatocellular carcinoma.
AB  - Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the
      genetic changes involved in cirrhosis are not well understood. We therefore
      studied loss of heterozygosity (LOH) in cirrhotic and neoplastic foci in livers
      of 14 patients with HCC. The samples, microdissected from paraffin-embedded
      tissues, were analyzed using a polymerase-chain-reaction-based assay for
      dinucleotide repeat polymorphisms on 8p. Of the 14 cases, 13 showed
      constitutional heterozygosity for the microsatellite markers. In 7 (54%) of these
      13 informative cases, LOH was detected in the primary HCC and, in these 7 doubly
      informative (informative and LOH-positive in primary HCC) cases, LOH was found in
      16 (70%) of 23 liver cirrhotic foci. The pattern of 8p allelic loss was identical
      in each doubly informative tumor; however, some of the liver cirrhotic foci
      harbored an 8p loss identical to that seen in the primary HCC, some harbored a
      different 8p loss, and some did not harbor any 8p loss. The remaining 6 cases
      without LOH on 8p in HCC showed no 8p loss in any cirrhotic foci. Presumably HCC
      could develop from cirrhotic cells harboring 8p loss.

PMID- 8879254
TI  - Treatment of clinical stage I testicular cancer and a possible role for new
      biological prognostic parameters.
AB  - Three different treatment strategies for patients with stage I non-seminomatous
      testicular cancer are available that will all result in long-term survival in
      more than 98% of the patients: a "wait and see" strategy with follow-up and
      chemotherapy in cases of tumour progression, retroperitoneal lymphadenectomy,
      with or without application of systemic chemotherapy, in cases of retroperitoneal
      metastases (pathological stage II disease) or primary adjuvant chemotherapy
      following inguinal orchiectomy. Each treatment strategy is associated with
      specific side-effects. In several studies histological characteristics of the
      primary tumour, particularly the presence of vascular invasion and of embryonal
      carcinoma cells, have been demonstrated to be significant prognostic factors for
      the risk of occult retroperitoneal metastases in patients with stage I disease.
      In addition, new biological prognostic factors determined by flow cytometry,
      cytogenetic analysis or molecular-biological DNA or RNA analysis have been
      investigated, among which alterations of the p53 tumour-suppressor gene may
      represent a promising new prognostic factor. Although alterations of p53 gene
      expression seem to be associated with advanced tumour stage and may predict
      retroperitoneal metastatic disease, the independent role of these molecular
      genetic alterations needs to be prospectively studied. Currently a risk-adapted
      treatment strategy based on the histological criteria of vascular invasion and
      the presence of embryonal carcinoma can be used to stratify patients into a "high
      " and "low-risk" group with respect to tumour progression. While primary-nerve
      sparing retroperitoneal lymphadenectomy or adjuvant chemotherapy with two cycles
      of platinum, etoposide and bleomycin may be appropriate for patients with a high
      risk (above 40%) for tumour progression, a "wait-and-see" strategy can be used
      for "low-risk" (less than 15% risk of progression) patients. Molecular
      investigations of prognostic factors may be able to improve further the
      stratification of patients into these different risk categories.

PMID- 8879256
TI  - Role of milky spots as selective implantation sites for malignant cells in
      peritoneal dissemination in mice.
AB  - We investigated the significance of milky spots for malignant cells in peritoneal
      dissemination using three mouse carcinomatous peritonitis models. P388 leukemia
      and Colon 26 cancer cells were labeled with bromodeoxyuridine (BrdU) and mice
      were inoculated intraperitoneally. After 24 h the greater omentum and the
      mesenterium were removed and stained immunohistochemically with anti-BrdU
      antibody. The labeled cells were found to have preferentially infiltrated into
      the milky spots in these specimens. Next, using B16 PC melanoma cells, which can
      be easily distinguished from the other cells by the intrinsic black melanin, the
      distribution of the melanoma cells was observed macro- and microscopically
      following intraperitoneal inoculation. The melanoma cells were similarly found to
      have selectively infiltrated into the milky spots in the omentum and mesenterium
      after 1 day. Moreover, the melanoma cells were growing and forming distinct
      metastic lesions within the milky spots 1 week later.

PMID- 8879257
TI  - Cytokinetic effects of cisplatin on diverse human head and neck carcinomas in
      vitro: dependence on the tumor sensitivity to cisplatin.
AB  - Studies performed with xenografted human head and neck carcinomas in vivo have
      demonstrated that the cytokinetic phenomena occurring under the influence of
      cisplatin closely correlate with the response of the tumors to therapy. The
      present paper analyses whether this correlation also exists in vitro. Four human
      head and neck carcinoma cell lines showing different degrees of sensitivity to
      cisplatin, as determined by the trypan blue exclusion assay, were investigated by
      flow cytometry at various intervals after administration of cisplatin. Early cell
      cycle blockades in the S phase always reflected a high degree of cytostatic
      potency of cisplatin and were usually succeeded by a pronounced inhibition of
      tumor cell proliferation and a reduction of cell viability. In the case of a
      minimal response to therapy and in untreated control cultures of all four tumor
      lines, the relative number of S-phase cells continuously diminished during the
      observation period. These findings point to the S-phase blockade as the crucial
      cytokinetic effect of cisplatin preceding relevant growth reductions. This
      knowledge might support the development of a drug-response assay that could
      predict the sensitivity of individual patient tumors in vitro before the
      beginning of clinical cancer chemotherapy.

PMID- 8879258
TI  - Cell-cycle arrest, micronucleus formation, and cell death in growth inhibition of
      MCF-7 breast cancer cells by tamoxifen and cisplatin.
AB  - The induction of cell death along with cell-cycle arrest is one of the foremost
      mechanisms regulating cell growth. In the human breast carcinoma cell line MCF-7
      we investigated two chemotherapeutic agents, the antiestrogen tamoxifen and the
      DNA-damaging drug cisplatin, for the relative contribution of these mechanisms to
      growth inhibition in culture. Growth kinetics and flow cytometry confirmed that
      tamoxifen at 1 microM acts mainly by arresting cells in the G0/G1 phase of the
      cell cycle. Compared to untreated controls, only a few more cells were detached
      from the monolayer and dead after a 5-day incubation. On the other hand,
      cisplatin at 1 microM did not induce the well-defined G2/M-arrest reported for
      other cell types, but resulted in a marked increase in the rate of cell death. A
      morphological feature observed, especially with cisplatin-treated MCF-7 cells,
      was the formation of numerous micronuclei (in up to 30% of the cells) and an
      increase in the number of binucleate cells (up to 20%). In both tamoxifen- and
      cisplatin- treated cultures, cell death appeared to occur by apoptosis, as
      indicated morphologically by cellular and nuclear shrinkage accompanied by DNA
      condensation and ultimately the formation of DNA containing apoptotic bodies.
      However, no internucleosomal DNA degradation or endogenous endonuclease activity
      could be detected in the cells of the monolayer or in the mainly dead and
      detached cells of the culture supernatant. DNA fragmentation was only observed
      when isolated MCF-7 nuclei were incubated with exogenous endonucleases. However,
      as determined by reverse transcriptase/polymerase chain reaction amplification,
      MCF-7 cells do express the mRNA for DNase I, an endonuclease known to be involved
      in apoptosis. Thus, apoptosis is part of the growth-inhibitory process and occurs
      without apparent internucleosomal DNA fragmentation in MCF-7 cell cultures.

PMID- 8879259
TI  - Effect of ethanol on esophageal cell proliferation and the development of N
      methyl-N'-nitro-N-nitrosoguanidine induced-esophageal carcinoma in shrews.
AB  - The effect of ethanol (EtOH) on esophageal cell proliferation and the development
      of esophageal cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in
      shrews were investigated. Sequential histological examination was done, and cell
      proliferation was assessed by BrdU labeling. At 5 weeks of age, animals were
      given tap water, 2% EtOH, 50 ppm MNNG, or 50 ppm MNNG plus 2%, 5% or 10% EtOH in
      the drinking water. Administration of 10% and 5% EtOH simultaneously with MNNG
      caused death in 40% (10/25) within 4 days and in 20% (6/30) within 7 days
      respectively, whereas other treatment were well tolerated with no sudden deaths.
      Administration of 2% EtOH for 30 weeks caused a 2-fold increase, and that of MNNG
      caused a 4.5-fold increase in the proliferation index of the basal cells of the
      esophagus compared with control shrews, and MNNG plus 2% EtOH caused a 5.5-fold
      increase. In MNNG-treated shrews, with or without 2% EtOH administration,
      sequential histological examination of esophageal tissue revealed a similar
      change; dysplasia appeared at 30 weeks of age, squamous cell carcinoma occurred
      at 35 weeks of age, and the depth of invasion extended to adventitia at 45 weeks
      of age. These finding indicate that treatment with 2% EtOH promoted the
      proliferation of esophageal basal cells but did not alter the tumor induction
      period and did not have tumor-promoting activity. EtOH per se was not
      carcinogenic; no tumors were seen in shrews not administered MNNG.

PMID- 8879261
TI  - Metastasis of chondrosarcoma.
AB  - This study was undertaken to analyse metastases of patients with intermediate- or
      high-grade chondrosarcomas. Out of 24 intermediate-grade tumours, 5 (21%)
      developed metastases, as did 6 of 10 high-grade tumours (60%) (P = 0.04). Four
      patients developed pulmonary metastasis only, 5 developed both pulmonary
      metastases and metastases of the other sites. Two patients showed a rare
      metastatic pattern: bone metastases only. The metastasis rate in the primary
      chondrosarcoma (42%) was higher than that in the secondary chondrosarcomas (0%)
      (P = 0.03). The metastasis rate was higher in patients with local recurrence
      (86%) than in those without local recurrence (19%) (P = 0.01). In 5 of 6 patients
      who had a local relapse and metastasis, the interval between the two relapses was
      a few months.

PMID- 8879260
TI  - Glutathione S-transferase expression in malignant mesothelioma and non-neoplastic
      mesothelium: an immunohistochemical study.
AB  - Expression of the glutathione S-transferase (GST) subclasses alpha, mu and pi was
      investigated immunohistochemically in 20 normal or hyperplastic mesothelium and
      in 57 malignant mesothelioma cases. These results were correlated with survival
      and also with P-170 glycoprotein expression. Nearly all the non-neoplastic
      mesothelium cases were positive for GST alpha and pi. About half of the non
      neoplastic cases were positive for mu. Twenty-nine (51%) malignant mesotheliomas
      were positive for at least one of the GST species; 21 (37%) showed
      immunoreactivity for alpha, 18 (31.5%) for mu and 21 (37%) for pi. A total of 54
      mesothelioma cases displayed immunoreactivity for the P-170 glycoprotein. For GST
      pi and GST mu, a statistical significance between expression and increased
      survival was found (respectively P = 0.012 and 0.024) while for GST alpha no
      significance was found. The results of this study demonstrate that expression of
      GST pi correlates positively with increased survival in malignant mesothelioma.
      It is also concluded that, in mesothelioma, GST and P-170 glycoprotein may
      contribute to the resistance to cytotoxic drugs frequently observed in these
      tumours. No correlation between GST and P-170 expression was demonstrated.

PMID- 8879262
TI  - Pain caused by bone metastasis in endocrine-therapy-refractory prostate cancer.
AB  - It is of clinical importance to control pain in the management of patients with
      endocrine-therapy-refractory prostate cancer. To evaluate factors influencing the
      manifestation of pain and the relationship between characteristics of pain and
      prognosis, patients with pain from bone metastasis were analyzed. A total of 48
      patients with endocrine-therapy-refractory prostate cancer, who showed
      progression of bone metastasis and were followed-up until death, comprised the
      present study. The patients were divided into three groups according to the grade
      of pain: no need for analgesics, a need for non-opioid analgesics, and a need for
      opioid analgesics. The time interval between the diagnosis of the endocrine
      therapy-refractory state and the requirement for analgesics was estimated.
      Survivals from the endocrine-therapy-refractory state were calculated according
      to the grade of pain or the time interval to requirement for analgesics. In
      addition, the extent of disease, the doubling time of tumor markers at the
      refractory state, any change of alkaline phosphatase, and other prognostic
      factors were examined in relation to pain. All 22 endocrine-therapy-resistant
      cases at initial treatment and 18 of 26 (69%) relapsed cases required analgesics
      during the clinical course until death. No difference in survival was observed
      between the grades of pain. The patients who needed analgesics within 1 year
      after becoming refractory to endocrine therapy showed significantly shorter
      survival than those without or with analgesics more than 1 year later. Although
      the time elapsing before analgesics were needed was not related to the extent of
      disease, the patients who showed a shorter doubling time for tumor markers and/or
      an exponential increase in alkaline phosphatase tended to require analgesics
      within 1 year. In endocrine-therapy-refractory prostate cancer, the early
      requirement for analgesics suggests poor prognosis, and the onset of pain may be
      attributable not to the extent of the disease but rather to the rapid expansion
      of bone metastasis.

PMID- 8879263
TI  - Signal transduction into the nucleus: fifth colloquium on cellular signal
      transduction. Heidelberg, Germany, January 1996.

PMID- 8879264
TI  - Genotoxic effects of metronidazole.
AB  - Metronidazole (MTZ) is an effective agent used in the treatment of parasitic
      infections. Its genotoxic effects have been shown in a variety of prokaryotic
      systems; however, negative results have been reported in human in vivo studies.
      Due to its wide spread use, a study was performed to evaluate the chromosomal
      aberration frequencies in peripheral blood lymphocyte cultures from 10
      individuals, before and after metronidazole treatment. A significant increase in
      the percentage of cells with chromatid and isochromatid breaks was observed after
      metronidazole treatment (1500 mg per day for 10 days). The percentages of cells
      with aberrations did not correlate with the levels of MTZ found in plasma.
      Individual variability was observed with respect to both the induction of
      aberrations and the concentration of MTZ in plasma. They could represent
      differences at the metabolic level, since metronidazole is known to be
      biotransformed by a polymorphic P450 cytochrome, and its metabolites have shown
      mutagenic activity.

PMID- 8879265
TI  - Enhanced cell permeability increases the sensitivity of a yeast test for
      mutagens.
AB  - ts1 is a mutation which causes a general increase in permeability of Sacharomyces
      cerevisiae cells in an unspecific manner. The introduction of the ts1 mutation
      under homozygous conditions into the D7 diploid strain enhanced the sensitivity
      of the test system described by Zimmermann et al. (1975). The newly constructed
      strain D7ts1 responded with a four to six times higher frequency compared to the
      D7 strain for all genetic end-points induced with chemical mutagens (ethyl
      methanesulfonate, methyl methanesulfonate, hydroxyurea, benzpyrene). The
      increased sensitivity of D7ts1 is specific only for mutagens active in yeast,
      since treatment of D7ts1 cells with 5-bromouracil or 5-bromouridine, known to be
      non-mutagenic in yeast, did not result in the induction of any of the measured
      genetic alterations. Five out of 14 water samples taken from the environment
      induced recombinogenic events in D7ts1, whereas all 14 water samples were without
      effect in the D7 test system. We concluded that D7ts1 cells show a higher
      sensitivity in the detection of mutagenic or carcinogenic action because of their
      generally enhanced permeability due to the ts1 mutation.

PMID- 8879266
TI  - Simultaneous immunoselection in vitro for H-Y or H-2D antigen-loss variants of a
      mouse-derived B cell line.
AB  - Cytotoxic T lymphocytes (CTL) specifically reactive with the male transplantation
      antigen (H-Y) were used to immunoselect in vitro for antigen loss among cells
      from an Abelson murine leukemia virus (AbMuLV) transformed lymphoblastoid cell
      line. Numerous variant cell clones were recovered that had lost expression of
      either H-Y or the restricting major histocompatibility class I molecule, H-2D. In
      all experiments, low-level gamma-irradiation applied prior to immunoselection
      increased the frequency of antigen loss, but when different time intervals
      between mutagenesis and immunoselection were used, the proportion of H-Y to H-2D
      antigen loss was affected, suggesting that the antigens selected against remain
      on the surface of the cell for differing amounts of time following allele loss.

PMID- 8879267
TI  - Assessment of the flexed-tail mouse as a possible model for Fanconi anemia:
      analysis of mitomycin C-induced micronuclei.
AB  - Fanconi anemia (FA) is a rare, autosomal recessive disorder characterized by
      elevated frequencies of chromosome aberrations, hypersensitivity to DNA cross
      linking agents and predisposition to cancer. At least 5 complementation groups
      (FA-A to FA-E) underlie FA and the gene defective in FA-C (FAC) has been cloned.
      The mouse orthologue, Fac, maps in close proximity to the f locus, on chromosome
      13, which codes for the flexed-tail mouse phenotype, raising the possibility that
      f and Fac are synonymous. If this were the case flexed-tail mice could be used as
      mouse models for FA-C to help determine the basic defect and to evaluate clinical
      intervention and gene therapy. To further characterize the flexed-tail mouse, the
      frequency of micronuclei (a measure of chromosomal aberrations) induced by
      mitomycin C (MMC), an alkylating and DNA cross-linking agent, was analyzed in
      peripheral blood and bone marrow erythrocytes. Although a higher spontaneous
      micronucleus frequency was seen in flexed tail mice in comparison to wild-type
      mice, the sensitivity to MMC was not elevated. This result suggests that f and
      Fac are different genes and that the flexed-tail mouse is not a model for FA-C.

PMID- 8879268
TI  - Cytogenetic effects in mice of divinylbenzene-55 inhalation.
AB  - Male B6C3F1 mice (8 weeks of age) were exposed by inhalation to divinylbenzene-55
      (DVB-55), at target concentrations of 0, 25, 50 and 75 ppm for 6 h per day for 3
      days. Following exposure the animals were killed blood smears were prepared for
      micronucleus (MN) analysis, and the spleens were removed and cultured for sister
      chromatid exchange (SCE) and chromosome aberration (CA) analyses. DVB-55 induced
      a dose dependent increase in SCE with the two highest doses reaching statistical
      significance. Similarly, there was a statistically significant although less
      pronounced increase in the frequency of CAs in splenocytes and MN in
      polychromatic erythrocytes. There was no indication of toxicity as measured by
      cell cycle kinetics in the splenocytes or the percentage of polychromatic
      erythrocytes in the peripheral blood smears. Thus, DVB-55 appears to be a weak
      genotoxicant in vivo.

PMID- 8879269
TI  - DNA damage in exfoliated buccal cells of smokers assessed by the single cell gel
      electrophoresis assay.
AB  - The alkaline single-cell gel electrophoresis assay or comet assay is a sensitive
      and rapid method for DNA strand breaks and detection of alkali labile sites at
      the single cell level, it further provides information on the presence of damage
      among individual cells. In this paper we explore the use of this technique
      utilizing exfoliated buccal mucosa cells from non-smokers (9 donors) and smokers
      (11 donors). The extent of DNA image length was found to be significantly
      increased in the smoker group (89.30 +/- 16.18 microns) than in the non-smoker
      group (52.01 +/- 10.43 microns). Our results indicate that the single-cell gel
      electrophoresis assay could be applied to human monitoring using exfoliated
      buccal epithelial cells.

PMID- 8879270
TI  - Effects of the amino acid glutamine on frequency of chromosomal aberrations
      induced by gamma radiation in Wistar rats.
AB  - The radiotherapy treatment of human cancer is often limited by the side effects
      and complications induced in normal surrounding tissues. The use of therapeutic
      strategies that could protect normal tissues while permitting the death of
      malignant neoplasm would be advantageous. Some studies have suggested that the
      amino acid glutamine (GLN) can serve as a conditionally essential nutrient in
      patients in a catabolic condition. The objective of this study was to evaluate
      the possible radioprotection of GLN on the frequency of chromosomal aberrations,
      number of metaphases with chromosomal aberrations and mitotic index in bone
      marrow cells of Rattus norvegicus. In this in vivo test system, GLN was
      administered by gavage at concentrations of 300 and 600 mg/kg body weight, in
      acute treatments, 30 min or 24 h before exposure to 3 Gy of whole-body gamma
      radiation. The results obtained in these experiments showed that GLN did not
      alter significantly the frequency of chromosome aberrations induced by gamma
      radiation under the experimental conditions used in the present study.

PMID- 8879271
TI  - Antimutagenic and anticarcinogenic activity of natural and synthetic
      curcuminoids.
AB  - Five synthetic curcuminoids and three natural curcuminoids were investigated for
      their antimutagenic and anti-promotional activity. The natural curcuminoids,
      curcumin I (diferuloylmethane), curcumin II (feruloyl-p-hydroxycinnamoylmethane)
      and curcumin III (bis-(p-hydroxycinnamoyl)methane) isolated from Curcuma longa
      were found to be potent inhibitors of mutagenesis and crotean oil-induced tumour
      promotion. Curcumin III produced 87.6% inhibition to 2-acetamidofluorene (2-AAF)
      induced mutagenesis, at a concentration of 100 micrograms/plate, curcumin II and
      curcumin I produced 70.5% and 68.3% inhibition at the same concentration. All the
      synthetic curcuminoids were found to inhibit 2-AAF-induced mutagenicity among
      which salicyl- and anisylcurcuminoids were the most active. Curcumin III was the
      most effective anti-promotor among natural curcuminoids. While 90% of the control
      animals were having papillomas on the 10th week of tumour initiation, only 10% of
      the curcumin III-treated animals, 20% of the curcumin II-treated animals, and 40%
      of the curcumin I-treated animals were having papillomas. Salicylcurcuminoid,
      which was causing no papillomas by the 10th week, was the most potent anti
      carcinogen among the synthetic curcuminoids. Piperonal curcuminoid also exhibited
      anti-promotional activity.

PMID- 8879272
TI  - Cloning of Schizosaccharomyces pombe rph16+, a gene homologous to the
      Saccharomyces cerevisiae RAD16 gene.
AB  - The RAD16 gene is involved in the nucleotide excision repair of UV damage in the
      transcriptional silenced mating type loci (Terleth et al., 1990 and Bang et al.,
      1992) and in non-transcribed stands of active genes in Saccharomyces cerevisiae
      (Verhage et al., 1994). Using touchdown-PCR with primers derived from various
      domains of the S. cerevisiae Rad 16 protein, a specific Schizosaccharomyces pombe
      probe was isolated. This probe was used to obtain the complete RAD16 homologous
      gene from a S. pombe chromosomal bank. DNA sequence analysis of the rph16+ gene
      revealed an open reading frame of 854 amino acids. Comparison of the amino acid
      sequences of the Rhp16 and Rad16 proteins showed a high level of conservation:
      68% similarity. The Rhp16 protein sequence contains the two Zn-finger motifs and
      the putative helicase domains as found in the Rad16 protein. Like the RAD16, the
      rph16+ gene is UV-inducible (Bang et al., 1995). In analogy with the rad16
      mutant, the rhp16 disruption mutant is viable and grows normally, indicating that
      the gene does not have an essential function. The rhp16 disruption mutant is not
      sensitive for UV but is sensitive for cisplatin. The rhp16+ gene cloned behind
      the GAI 1 promoter partially complements the UV sensitivity and the defect in the
      non-transcribed strand DNA repair of a S. cerevisiae rad16 mutant, indicating
      functional homology between the rhp16+ and RAD16 genes. The structural and
      functional homology between the two genes suggests that the RAD16 dependent
      subpathway of NER for the repair of non-transcribed DNA is evolutionary
      conserved.

PMID- 8879273
TI  - Absence of UV-induced non-homologous recombination in repair-deficient CHO cell
      lines transfected with ERCC genes.
AB  - The nucleotide excision repair pathway removes a broad spectrum of DNA lesions,
      including UV-induced damage. To ascertain whether the repair of the latter has a
      causative role in the enhancement of non-homologous recombination, Chinese
      hamster CHO cell lines proficient and deficient in the ability to repair UV
      induced damage were transfected with a plasmid containing the bacterial neoR
      gene. Following UV-treatment an enhancement of non-homologous recombination above
      the spontaneous level was observed in repair-proficient cells, whereas no
      increase was observed in repair-deficient cell lines. Hence, the latter were
      transfected with the corresponding excision repair cross complementing human
      genes and the resulting repair-proficient transfectants were tested for UV
      induced non-homologous recombination. In both untreated and UV-treated
      transfectants, the frequencies of the event were not significantly different.
      Cumulatively, the results suggest that non-homologous recombination induced by UV
      irradiation is not restored by the correction of the excision repair defect.

PMID- 8879274
TI  - Self-association of human RAD52 protein.
AB  - The yeast RAD52 protein is required for both homologous DNA recombination and
      repair of DNA double-strand breaks. RAD52 can bind to the yeast RAD51 protein,
      which shares a functional similarity with the bacterial RecA protein. The gene
      encoding the human homolog of the yeast RAD52 protein shares significant N
      terminus amino acid homology with the yeast RAD52 protein. Using a yeast two
      hybrid system and purified GST-RAD52 fusion protein, we demonstrate that the
      human RAD52 protein self-associates both in vivo and in vitro. The region of
      RAD52 required for its self-interaction, mapped here as amino acid residues 65
      165, has significant homology with the yeast RAD52 (52% identity, and 89%
      similarity), suggesting the importance of self-association for RAD52's function.

PMID- 8879275
TI  - The defect in the AT-like hamster cell mutants is complemented by mouse
      chromosome 9 but not by any of the human chromosomes.
AB  - X-ray sensitive Chinese hamster V79 cells mutants, V-C4, V-E5 and V-G8, show an
      abnormal response to X-ray-induced DNA damage. Like ataxia telangiectasia (AT)
      cells, they display increased cell killing, chromosomal instability and a
      diminished inhibition of DNA synthesis following ionizing radiation. To localize
      the defective hamster gene (XRCC8) on the human genome, human chromosomes were
      introduced into the AT-like hamster mutants, by microcell mediated chromosome
      transfer. Although, none of the human chromosomes corrected the defect in these
      mutants, the defect was corrected by a single mouse chromosome, derived from the
      A9 microcell donor cell line. In four independent X-ray-resistant microcell
      hybrid clones of V-E5, the presence of the mouse chromosome was determined by
      fluorescent in situ hybridization, using a mouse cot-1 probe. By PCR analysis
      with primers specific for different mouse chromosomes and Southern blot analysis
      with the mouse Ldlr probe, the mouse chromosome 9, was identified in all four X
      ray-resistant hybrid clones. Segregation of the mouse chromosome 9 from these
      hamster-mouse microcell hybrids led to the loss of the regained X-ray-resistance,
      confirming that mouse chromosome 9 is responsible for complementation of the
      defect in V-E5 cells. The assignment of the mouse homolog of the ATM gene to
      mouse chromosome 9, and the presence of this mouse chromosome only in the
      radioresistant hamster cell hybrids suggest that the hamster AT-like mutant are
      homologous to AT, although they are not complemented by hamster chromosome 11.

PMID- 8879276
TI  - The identification and characterization of mammalian proteins involved in the
      rejoining of DNA double-strand breaks in vitro.
AB  - Using a combination of specific assays and biochemical fractionation of mammalian
      extracts, we have identified multiple activities involved in the rejoining of DNA
      double-strand breaks. Fractionation of whole cell extracts from calf thymus has
      identified four biochemically distinct fractions capable of joining double-strand
      breaks, and an activity Rejoin Enhancement Protein (REP-1), that stimulates this
      process. We also show that REP-1 directly stimulates a DNA ligase and that this
      stimulation is associated with the increased turnover of the adenylated
      intermediate formed by all ATP-dependent DNA ligases. Activity relationships
      between the rejoining fractions and REP-1 indicates that the joining of double
      strand breaks is carried out by protein complexes of which REP-1 is a component.
      In support of this, the cellular activities identified here that can efficiently
      rejoin double-strand breaks, do not show detectable adenylation products. Western
      analysis also shows that several proteins that have been suggested to be involved
      in the joining of double-strand breaks, such as the Ku heterodimer, are not
      present in all fractions that contain rejoining activity. These data strongly
      suggests that many different activities exist that can rejoin double-strand
      breaks and that this process is not dependent on the presence of proteins such as
      the end-binding protein Ku.

PMID- 8879277
TI  - The effect of donor age on the processing of UV-damaged DNA by cultured human
      cells: reduced DNA repair capacity and increased DNA mutability.
AB  - Aging in humans carries an increased risk of skin cancer, a disorder linked to
      somatic mutations in sun damaged skin. DNA repair plays a major role in
      protection against sun damage. We found an age-related decline in post-UV DNA
      repair capacity (measured by the ability to repair a UV-treated plasmid
      (pCMVcat)) of-0.6% per year (p = 0.0001) in cultured primary skin fibroblasts
      from normal donors from the first to the tenth decade of life. There was a
      corresponding age-related increase in post-UV mutability (measured as mutations
      introduced into a transfected, UV-treated plasmid (pSP189)) of +0.6% per year (p
      = 0.001) in lymphoblastoid cell lines from normal donors of the same age range.
      This study indicates that aging in humans is associated with decreasing ability
      to process new UV-induced DNA damage and this age-related reduction in DNA repair
      capacity and increase in DNA mutability is reflected in cultured skin and blood
      cells.

PMID- 8879278
TI  - An improved method of alkaline sucrose density gradient sedimentation to detect
      less than one lesion per 1 Mb DNA.
AB  - We improved alkaline sucrose density gradient sedimentation to detect very long
      single-strand DNA at the megabase level (from less than 1 to about 4 Mb).
      Hitherto, these have not sedimented correctly due to some artifacts. One artifact
      was aggregation of sticky DNA and proteins formed in the gradient. Then, in some
      gradients, biphasic distribution was observed, the major peak of which was
      reasonable as a result of random scission by X-rays, but the minor, fast
      sedimenting population was another artifact resulting from incomplete
      denaturation of the DNA. We mainly reduced the centrifugal force and used a
      solution for cell lysis with a high concentration of salt. By means of this
      procedure, DNA single-strand breaks induced by relatively low doses of X-rays and
      subsequent repair processes can be measured in human fibroblasts. The protocol is
      also applicable to the study of DNA damage accompanied by strand scission, such
      as by UV or dimethyl sulfate as well as their repair. The technique is sensitive
      enough to detect even single-strand breaks induced by 0.1 J/m2 UV and
      sufficiently reproducible that breaks induced by increasing UV dosages were dose
      dependent. Thus, this technique was proven to be very sensitive, reliable and
      simple to perform. Therefore, this improvement will be extremely useful to
      investigators studying DNA repair.

PMID- 8879279
TI  - Alcohol dependence: a commentary on mechanisms.
AB  - The alcohol dependence syndrome includes the presence of alcohol tolerance,
      physical dependence and an inability to control one's alcohol intake. Studies are
      reviewed that implicate the mesolimbic dopaminergic systems, and the gamma
      aminobutyric acid-A (GABAA) and N-methyl-D-aspartate (NMDA) receptors as
      mediators of various aspects of the alcohol dependence syndrome. It is suggested
      that alcohol-induced changes in the GABAA receptor may play a role in certain
      aspects of tolerance to alcohol and in altered abilities of an individual to
      terminate alcohol intake. Chronic alcohol-induced increases in the activity of
      NMDA receptors may contribute to the withdrawal signs that are the defining
      feature of physical dependence on alcohol. It is hypothesized that decreased
      mesolimbic dopaminergic function, which occurs during alcohol withdrawal, may be
      involved in the compulsion to initiate and maintain alcohol drinking, another
      aspect of the alcohol dependence syndrome. Furthermore, evidence is presented
      that this decreased dopaminergic function could occur secondarily to the increase
      in NMDA receptor function, such that the alcohol-induced increase in NMDA
      receptor function could underlie both the overt withdrawal signs and the
      compulsion to drink alcohol in the alcohol-dependent individual.

PMID- 8879280
TI  - An open multicentric study evaluating 4-hydroxybutyric acid sodium salt in the
      medium-term treatment of 179 alcohol dependent subjects. GHB Study Group.
AB  - We report the results of an "open' multicentre study evaluating the use,
      tolerability and therapeutic efficacy of the sodium salt of 4-hydroxybutyric acid
      (GHB) for the medium-term treatment of withdrawal symptoms in 179 patients with
      alcohol dependence followed up as outpatients. The follow-up of patients was 6
      and 12 months after drug discontinuation. Following a daily oral administration
      of 50 mg/kg for approximately 6 months, no serious systemic or single-organ
      consequences leading to drug discontinuation were reported, and tolerability was
      fair in all patients. Eleven subjects (10.1%) showed craving for the drug and
      voluntarily increased their doses (6-7 times the recommended levels). GHB led to
      complete abstinence during drug administration in 78.0% of the patients. A
      significant reduction of compulsive desire ("craving') was observed in parallel,
      as deduced from evaluation of a specific questionnaire, the Alcohol Craving
      Scale. At follow-up examination, 43 of the treated subjects remained abstinent at
      6 months, and 30 subjects were abstinent for 1 year after drug discontinuation.

PMID- 8879281
TI  - Ethanol withdrawal hyperexcitability in vivo and in isolated mouse hippocampal
      slices.
AB  - Withdrawal hyperexcitability was seen in isolated mouse hippocampal slices,
      prepared after chronic treatment with ethanol, by inhalation for 2 weeks. The
      pattern of hyperexcitability differed from those seen previously when a different
      method of ethanol administration and a different strain of mice were used.
      Thresholds for field potentials were decreased, but the transient increase in
      paired pulse potentiation, reported earlier, was not evident. Chronic
      administration of the calcium channel antagonist, isradipine (PN-200-110) during
      ethanol treatment significantly decreased the withdrawal syndrome, both in vivo
      and in vitro. Brain concentrations of isradipine during the test period were
      found to be sufficient to produce acute effects on the withdrawal
      hyperexcitability. No changes were seen in the field potentials when slices were
      prepared after treatment with isradipine alone. A small, but significant,
      increase in excitability was seen in vivo after the treatment with isradipine
      alone. Previous studies showed that isradipine did not protect against the
      hyperexcitability due to gamma-aminobutyric acid (GABA)A antagonism, so the
      results suggest that neuronal calcium channels may be involved in ethanol
      withdrawal hyperexcitability, but decreases in GABAA inhibition may not be
      important.

PMID- 8879282
TI  - A comparison of two techniques to reach relatives of alcoholics for information
      of available support.
AB  - Two different information techniques to reach spouses and relatives of inpatient
      alcoholics for information of available support, one standardized and one
      individualized, were compared. Each procedure was tested during 6 months in the
      same ward. In the standardized model 18% (20/112) and in the individualized model
      20% (21/104) of spouses/relatives/friends attended the information session. In
      those living with a spouse, the rates were 46% and 41% respectively, and among
      those who were not cohabiting, but had relatives or sober friends, the figures
      were 11% and 17% respectively. There were no sex differences. Among preferred
      support, individual support, marital and family support and professional group
      support received the highest ratings. At the 1 year follow-up, more subjects in
      the individualized information group had received support compared with those in
      the standardized group. The low rates of informed subjects are in agreement with
      the literature and considerably lower than the rates in information programmes
      for relatives of schizophrenic patients.

PMID- 8879283
TI  - Development and application of a physiologically based pharmacokinetic model for
      ethanol in the mouse.
AB  - The purpose of the present study was to develop a physiologically based
      pharmacokinetic (PBPK) model in the mouse and to utilize it to evaluate the
      relative contribution, if any, of gastric alcohol dehydrogenase (ADH) to the
      bioavailability of ethanol. The PBPK model developed in Swiss Webster male mice
      accurately simulated blood and brain ethanol concentrations following an
      intraperitoneal administration of 0.82 and 3.2 g of ethanol/kg body weight.
      Application of the model illustrated that inclusion of gastric ADH into the model
      provided a less accurate fit to the experimental data, and therefore gastric ADH
      did not contribute to the overall disposition of an orally administered ethanol
      dose of 0.75 g/kg. Furthermore, the model also indicated that changes in
      percentage cardiac output to the liver had a minimal effect on the blood ethanol
      concentration (BEC) time curve. The results illustrate the validity of the PBPK
      model developed for ethanol and demonstrate that in the Swiss Webster male mouse
      the bioavailability of ethanol is minimally affected, if at all, by metabolism by
      gastric ADH.

PMID- 8879284
TI  - Relative kindling effect of readmissions in alcoholics.
AB  - To determine if there is an increase in the risk of seizure activity when
      patients experience recurrent alcohol detoxification, the histories of 360
      alcoholics who had at least two admissions for alcohol detoxification, between
      November 1987 and August 1992, were reviewed retrospectively. All subjects were
      treated with tapering doses of chlordiazepoxide as required, to control
      symptoms/signs of alcohol withdrawal. Subjects with a seizure history were
      prophylactically treated with tapering doses of chlordiazepoxide. No seizures
      were observed during detoxification in any of these subjects. In this group of
      readmitted subjects, there was no correlation between self-reported duration of
      alcohol consumption or average daily intake of alcohol. A significant correlation
      was observed between seizure history and number of detoxification admissions and
      neurological admissions, but not for other medical/surgical admissions, nor for
      admissions for rehabilitation. At the time of initial admission, laboratory
      parameters did not distinguish those subjects with seizures from those without.
      At the time of readmission, mean corpuscular volume and gamma-glutamyl
      transpeptidase, both markers of alcohol consumption, were higher in the group
      with seizures.

PMID- 8879285
TI  - Should tri-sialo-transferrins be included when calculating carbohydrate-deficient
      transferrin for diagnosing elevated alcohol intake?
AB  - CDT (carbohydrate-deficient transferrin) has been identified as a specific marker
      for chronically elevated alcohol consumption. We investigated the sensitivity and
      accuracy of using relative concentrations of different isotransferrins in serum
      for diagnosis of chronically elevated alcohol consumption. The different
      transferrin variants (isoforms) were quantified by HPLC. Including the trisialo
      transferrin fraction into the definition of %CDT resulted in an increased
      accuracy in the detection of chronically elevated alcohol intake in a study among
      17 heavy drinkers, 25 healthy individuals with moderate alcohol consumption and
      nine total abstainers. The results also suggest that desialylation of transferrin
      is a gradually continuing process, rather than one leading to a single end-result
      separating asialo-, mono- and disialo-transferrins from trisialo-, tetrasialo-,
      pentasialo- and higher sialo-transferrins.

PMID- 8879286
TI  - Circadian drinking pattern of Sardinian alcohol-preferring rats.
AB  - The present study was designed to assess the temporal pattern of ethanol intake
      over a 24 h period in selectively bred, Sardinian alcohol-preferring (sP) rats.
      Ethanol intake occurred under the two-bottle, free choice regimen. sP rats
      consumed ethanol in three distinct peaks, rather regularly distributed over the
      12 h dark phase of the light-dark cycle and positively correlated with food
      intake episodes. The temporal distribution of ethanol intake and estimated blood
      alcohol levels are consistent with the hypothesis that sP rats voluntarily drink
      ethanol for its pharmacological effects.

PMID- 8879287
TI  - Increased carbohydrate-deficient transferrin during pregnancy: relation to sex
      hormones.
AB  - Controversy exists whether carbohydrate-deficient transferrin (CDT) is valuable
      as a screening tool for fetal alcohol syndrome. We evaluated serum CDT in 60 non
      alcohol-abusing women at different stages of normal pregnancy. CDT was weakly
      related to week of pregnancy and to human placental lactogen. CDT did not
      correlate with iron oestradiol or progesterone. By contrast, good correlations
      were found between transferrin and week of pregnancy or either sex hormone. Using
      multiple linear regression analysis, only transferrin and week of pregnancy were
      important predictors of CDT. The diagnostic accuracy of CDT for detecting alcohol
      abuse may be limited in pregnant women and should be carefully assessed in
      relation to alcohol consumption.

PMID- 8879288
TI  - Alcohol-related admissions to an inner city hospital intensive care unit.
AB  - We investigated the impact of alcohol-related medical emergencies on health care
      utilization in an inner city hospital medical intensive care unit (ICU). Data
      from 200 consecutive admissions to the medical ICU were collected prospectively.
      The major reason for each patient's admission to the ICU was recorded and the
      causal relationship between alcohol abuse and the admission diagnosis was
      determined. Clinical and demographic data as well as the insurance status and
      cost of goods and services delivered were determined for all patients. Twenty-one
      per cent of all the ICU admissions were directly alcohol-related, with a mean
      hospital charge of $52,527. The alcohol-withdrawal syndrome was the commonest
      alcohol-related admission, with a mean ICU stay of 5 days and a mean hospital
      charge of $21,336. Of the patients with non-alcohol related admission diagnoses,
      61% had health insurance, compared to 42% for the patients with alcohol-related
      admission diagnoses (P < 0.05). Patients with alcohol-related admissions tended
      to be younger and male. In conclusion, we demonstrated that alcohol-related
      admissions are common in inner city hospital ICUs and consume considerable
      hospital resources. The treatment of these patients is costly, with
      hospitalization being essentially non-curative. In this era of health care
      reform, more effective primary and secondary preventative measures are required
      to control this pervasive health care problem.

PMID- 8879289
TI  - Carbohydrate-deficient transferrin measured by high-performance liquid
      chromatography and CDTect immunoassay.
AB  - Carbohydrate-deficient transferrin (CDT) was measured in three populations using
      anion-exchange chromatography followed by radioimmunoassay (CDTectTM) and a new
      high-performance liquid chromatography (HPLC) method. The correlation between the
      methods in 50 consecutive clinical samples was good (r = 0.87). However, in a set
      of 49 samples with CDT concentrations close to the reference value of the
      methods, the correlation was low (r = 0.51). In addition, among controls, no
      correlation between the methods was found (r = 0.10). Abnormal isoforms of
      transferrin were noted in 5% of the clinical samples. HPLC determination of CDT
      offers the advantage of identifying these isoforms of transferrin and thus
      reducing analytical pitfalls associated with the CDTectTM method.

PMID- 8879290
TI  - Prevention of ethanol-induced changes in reactive oxygen parameters by alpha
      tocopherol.
AB  - Rats were given a 200 mg/kg body weight daily dose of alpha-tocopherol by i.p.
      injection for 15 days. This resulted in elevated levels of glutathione in both
      liver and brain, and in a reduced hepatic rate of generation of reactive oxygen
      species. The depression of hepatic and cerebral glutathione levels in ethanol
      consuming rats was prevented by simultaneous treatment with alpha-tocopherol.
      Other putative indices of hepatic pro-oxidant events, namely levels of mixed
      function oxidase and proteolytic activity, were elevated by alpha-tocopherol both
      in the presence and absence of ethanol. In addition, levels of enzymes especially
      susceptible to oxidative degradation, glutamine synthetase and creatine kinase,
      were depressed in the liver following treatment with ethanol or alpha-tocopherol.
      Parameters rapidly responsive to oxidative changes revealed the antioxidant
      property of alpha-tocopherol, while protein-based indices reflecting more
      extended events suggested a pro-oxidant effect of this vitamin. Results suggest
      that high levels of alpha-tocopherol can simultaneously lead to a more reduced
      intracellular environment and yet to localized evidence of enhanced oxidative
      events.

PMID- 8879291
TI  - No loss of somatostatin-immunoreactive neurons in the hippocampal dentate hilus
      of alcohol-withdrawal-kindled rats.
AB  - The neuropeptide somatostatin has been suggested to play a role in seizure
      genesis, electrical kindling and the neurotoxic effects of alcohol. The purpose
      of the present experiment was to study somatostatin-immunoreactive (SS-IR)
      neurons in hippocampus during alcohol-withdrawal kindling. Alcohol-withdrawal
      kindling was performed by subjecting male Wistar rats to seven weekly episodes
      consisting of 2 days of severe alcohol intoxication and 5 days of alcohol
      withdrawal. Then the kindled animals (multiple withdrawal group) and a single
      withdrawal group, which was fed isocalorically with the kindled animals during
      episodes 1-7, were exposed to 4 days of severe alcohol intoxication (episode 8).
      During the following withdrawal, the seizure activity was observed 9-15 h after
      last alcohol dose, in order to subdivide the animals from these two groups into
      groups with and without seizures. Subsequently, SS-IR neurons were visualized
      immunocytochemically and counted in the hilus of the dentate gyrus (hippocampus).
      The number of SS-IR neurons per unit area of the hilus was neither affected by a
      single nor by multiple episodes of alcohol withdrawal. We therefore concluded
      that a loss of these neurons is not involved in the development of alcohol
      withdrawal-kindled seizures.

PMID- 8879292
TI  - Thiamine deficiency as predisposition to, and consequence of, increased alcohol
      consumption.
AB  - It was found that the activity of the marker thiamine-dependent enzyme,
      transketolase (TK), was decreased (down to 61-79% of control) in blood, liver and
      brain of inbred rats following a 6-month consumption of 15% ethanol as their only
      source of drinking fluid. After ethanol withdrawal, the enzyme activity was
      gradually restored, but did not reach the control values until 1 month following
      cessation of alcohol consumption. Moreover, in rats preferring ethanol, the
      decrease of TK activity was more pronounced than in water-preferring rats.
      Another experiment showed that thiamine deficiency induced by the thiamine
      antagonist, oxythiamine (200 mg/kg), led to a prolonged increase of the
      preferential intake of ethanol solutions in inbred rats. Significantly lower
      liver TK activities and thiamine pyrophosphate content were found in Finnish AA
      line rats as opposed to ANA line rats which had been obtained by selective
      outbreeding for high and low voluntary alcohol intake, respectively.
      Significantly lower TK activity was also found in the whole brain (89%),
      cerebellum (79%) and pons-medulla oblongata (87%) of AA rats as compared to ANA
      animals. Our own findings and the literature data confirm the hypothesis that
      thiamine deficiency can be both predisposing to and a consequence of, increased
      alcohol consumption.

PMID- 8879293
TI  - Sub-populations of alcohol-dependent patients: differences in psychological
      functioning between high- and low-frequency alcohol consumers.
AB  - The purpose of the present study was to examine the processes underlying relapse
      to drinking using objective biological validation of self-reported recent alcohol
      consumption, using the ratio of 5-hydroxytryptophol to 5-hydroxyindol-3-ylacetic
      acid (5-HTOL/5-HIAA), a new biological marker to detect single episodes of
      drinking, in a sample of 38 male alcohol-dependent patients (DSM-III-R) who were
      assessed prospectively in terms of their clinical symptomatology over a 6-month
      treatment period. Results showed that nearly all patients obtained positive 5
      HTOL/5-HIAA samples during the course of treatment. However, upon closer
      inspection, results revealed a bimodal distribution for alcohol intake with high
      and low frequency of consumption episodes. Results showed that high frequency
      consumers obtained higher ratings of clinical symptoms as measured by the
      Comprehensive Psychopathological Rating Scale (CPRS) and by the St Goran's Semi
      structured Interview (SGSI) compared to low frequency alcohol consumers on
      symptoms of inner tension, lack of initiative, risk of relapse (as rated by
      therapists and as rated by patients themselves), dysphoria, negative craving for
      alcohol, and positive craving for alcohol. The present results provided evidence
      for the existence of two sub-populations of alcoholics, those who have frequent
      lapses and those who have low frequency of sporadic lapses. Further, these two
      sub-populations were shown to differ with respect to overall psychological
      functioning, and craving for alcohol. In conclusion, the present findings have
      important treatment implications in that reliable identification of patients'
      consumption patterns using biological markers would allow for the design of
      individually tailored treatment needs.

PMID- 8879294
TI  - Morphological stages of pilomatricoma.
AB  - In 1983, Ackerman proposed that pilomatricoma represents an infundibular-matrix
      cyst in its early stages. To study the evolution of this cystic neoplasm, we
      examined 118 lesions from 116 patients with pilomatricoma histopathologically and
      categorized the lesions into four distinct and chronological stages: early, fully
      developed, early regressive, and late regressive. Early lesions (eight cases)
      were small cystic structures lined by squamoid and basaloid epithelium containing
      keratin filaments and faulty hair matrix material composed of shadow cells. Fully
      developed lesions (27 cases) were large neoplasms lined by basaloid epithelium at
      their periphery, and within, composed of irregularly shaped, densely packed zones
      of cornified masses containing shadow cells. Early regressive lesions (37 cases)
      had no apparent epithelial lining but did have basaloid cell foci at the
      periphery; within, they were composed of pink hair matrix material with shadow
      cells surrounded by granulation tissue with inflammatory infiltrate and
      multinucleated histiocytic giant cells. Late regressive lesions (42 cases) had no
      epithelial component and were composed of irregularly shaped, partially confluent
      masses of faulty hair material, and calcified (and sometimes metaplastically
      ossified) shadow cells embedded in a desmoplastic stroma, with little or no
      inflammatory infiltrate. In four cases, there was a relatively large dermal
      nodule composed of several interconnected lobules that consisted largely of
      basaloid cells with only a few areas of shadow cells. We interpreted these
      lesions as proliferating pilomatricomas. Based upon our histopathologic findings,
      we propose that pilomatricomas may be categorized into four distinct
      morphological stages and that these stages reflect the "life" of a pilomatricoma.
      Thus, the lesion begins as an infundibular matrix cyst and ends up as a calcified
      and ossified nodule with no visible epithelial component.

PMID- 8879295
TI  - Detection of apoptosis by in situ labeling in pilomatricoma.
AB  - Pilomatricoma is a benign epidermal appendage tumor with differentiation toward
      hair cortex cells. It is composed of varying percentages of basophilic cells,
      shadow cells, and transitional cells. Transitional cells seem to be apoptotic
      cells as evidenced by their morphological and ultrastructural characteristics. We
      investigated apoptosis in ten specimens of pilomatricoma by the transferase
      mediated dUTP-biotin nick end labeling (TUNEL) technique. TUNEL-positive
      structures were detected in both transitional cell and amorphous debris zones,
      but not in either basophilic cell or shadow cell zones. In the transitional cell
      zone, apoptotic cells were found either in groups or bands, while in the
      amorphous debris zone, apoptotic bodies of varying sizes were seen diffusely.
      These findings indicate that transitional cells, due to the fact that they are
      dying cells, may not differentiate into the shadow cells. This view is supported
      by the facts that the transition of basophilic cells into the shadow cells is
      abrupt in some areas and that tumor cells, with or without ultrastructural
      characteristics of apoptosis, are found in the transitional cell zone.
      Furthermore, ultrastructural nuclear changes in shadow cells are different from
      those seen in apoptosis. Therefore, we propose that the name of transitional
      cells should be changed to "condensed cells." Although it has been conventionally
      though that basophilic cells in pilomatricoma differentiate directly and/or via
      transitional cells into shadow cells, we demonstrate that basophilic cells
      undergo two different processes. The first is differentiation directly into
      shadow cells, an the second is passage, via "condensed cells" (transitional
      cells), into the amorphous debris that results from tumor kinetics.

PMID- 8879296
TI  - Histopathology of cutaneous changes in non-drug-induced coma.
AB  - To compare the histological features of non-drug-induced and drug-induced coma
      blister, we performed histopathological and immunopathological studies of four
      biopsy specimens from three patients with non-drug-induced coma. These results
      were compared with the previously well-documented histology of drug-induced coma.
      The findings of the present study of non-drug-induced coma included (a) a
      variable degree of epidermal cell degeneration, including vacuolation of basal
      cells, intraepidermal blister formation with pale cytoplasm, and extensive
      coagulation necrosis with pale nuclei; (b) alteration of the outer root sheath of
      telogen follicles, ranging from focal necrosis to total coagulation necrosis, and
      degeneration of sebaceous gland with disappearance of the germinative cell layer;
      (c) secretory eccrine cells with pyknotic nuclei, vacuolation of the cytoplasm,
      and intercellular edema, resulting in poorly defined cytoplasm, although the
      nuclei of the outer basal layer were partially preserved; (d) from slight edema
      of the vessel wall of the venules to fibrinoid, thrombosis and/or fibrinoid
      necrotic degeneration of arterioles and venules; and (e) deposits of
      immunoglobulins or complement as detected by direct immunofluorescent technique
      in all the three cases. One significant difference between non-drug-induced and
      drug-induced coma blister was the presence of fibrinoid thrombi in the lumina of
      non-drug-induced coma blisters. Since one of the three cases of non-drug-induced
      coma studied in the present report did not show thrombi in the lumina, this
      feature may not always be available for the differential diagnosis of these two
      conditions. However, fibrinoid thrombi may be a good marker for the
      differentiation of these two conditions, when the depth and duration of non-drug
      induced coma are severe enough to induce these lesions.

PMID- 8879297
TI  - Prognostic significance of Ki-67 and p53 immunoreactivity in cutaneous squamous
      cell carcinomas.
AB  - In this retrospective study we have investigated the expression of Ki-67 and p53
      in 175 random cases of cutaneous squamous cell carcinomas by using the monoclonal
      antibodies MIB-1 and DO-1, respectively. The expression of these antibodies was
      compared with various histological parameters of prognostic significance. The
      staining results were also compared with the clinical outcome of the patients.
      MIB-1 and DO-1 staining showed statistically significant correlation with
      histopathological grade of the tumor (p < 0.0001 and p = 0.0016, respectively).
      The degree of immunolabelling of these antibodies also showed significant
      correlation with tumor depth and tumor thickness (MIB-1 thickness p = 0.02 and
      depth p = 0.026, and DO-1 thickness p = 0.014 and depth p = 0.005). The majority
      of the squamous cell carcinomas in our series were Clark's level IV, which
      therefore did not correlate with the extent of immunoreactivity (MIB-1, p =
      0.098; and DO-1, p = 0.885). Mean length of clinical follow-up was 5.2 years.
      Aggressive tumor behaviour was seen in 17 patients (10.6%) with 6.9% and 3.4%
      local recurrences and nodal metastasis respectively. A total of 89.4% patients
      remained disease-free following their definitive surgical treatment. Vulval skin
      represented the commonest site associated with unfavourable clinical outcome
      (five of 17 cases). A large number of squamous cell carcinomas in this poor
      prognosis group showed a high prevalence of immunoreactivity of the antibodies
      but this did not achieve any statistical significance. We conclude that Ki-67 and
      p53 expression in cutaneous squamous carcinoma is not an independent predictor of
      prognosis.

PMID- 8879298
TI  - Quantitative morphology of collagen fibers in cutaneous malignant melanoma and
      melanocytic nevus.
AB  - Since tumor growth and metastastatic spread are considered to depend on tumor
      stroma interaction, the present study describes the architecture of collagen
      fibers in 12 cases each of primary melanoma (vertical tumor thickness > 1 mm) and
      common melanocytic nevi in azan-stained sections by using automated image
      analysis. In each case, at least 100 high-power fields were consecutively sampled
      from the tumor center, the tumor periphery, and the surrounding normal-appearing
      reticular dermis. In both diagnostic groups, collagen density (amount of collagen
      per tissue volume) and mean collagen fiber bundle diameter was significantly
      lower in the tumor periphery than in the surrounding stroma and again lower in
      the tumor center than in the tumor periphery. When melanomas and nevi were
      compared with each other, melanomas had fewer, but thicker, collagen bundles than
      did nevi, particularly at the tumor periphery. Taking the mean values of each
      case as classifiers in multivariate logistic regression analysis, 21 of 24 cases
      were correctly classified (chi-squared test, p < 0.0001), indicating that the
      parameters of collagen architecture at least in part reflect biological
      differences between benign and malignant melanocytic skin lesions.

PMID- 8879299
TI  - The hybrid epidermoid and apocrine cyst. A combination of apocrine hidrocystoma
      and epidermal inclusion cyst.
AB  - We describe four cases of unusual superficial cutaneous cysts that have a lining
      epithelium composed of apocrine cells immediately adjacent to keratinizing
      squamous epithelium with an intact granular layer. Two of the cysts were on the
      nipple of the breast and two of the cysts were on the face. The lumina of all
      four cysts contained keratin. Immunoperoxidase staining for carcinoembryonic
      antigen in the facial cysts showed positive staining within the apocrine cells of
      the lining epithelium in one case. The pathogenesis of these lesions is
      uncertain. We suggest that these unusual cysts be called hybrid epidermoid and
      apocrine cysts.

PMID- 8879300
TI  - An immunohistochemical study of p53 protein expression in classical Kaposi's
      sarcoma.
AB  - The present study was performed to determine the frequency of p53 protein
      immunoreactivity in classical Kaposi's sarcoma (KS) as a whole and in relation to
      the histological subtypes which are considered to correspond to the developmental
      stages of the tumor. The accumulation of p53 protein was studied
      immunohistochemically using monoclonal antibody BP53-12 on formalin-fixed
      paraffin-embedded sections of 36 KS lesions, of which 14 were classified
      histologically as early type and 22 as spindle-cell or mixed type. No positive
      immunoreactivity was detected in any of the 14 early-type lesions. Among the 22
      spindle-cell and mixed variants, positive staining was detected in 5-10% of the
      tumor cells in one lesion, 1-5% of the cells in six lesions, and in < 1% of the
      cells in two lesions. These very small percentages of positively stained cells in
      less than half of the cases of the spindle-cell and mixed variants do not support
      a significant role for p53 in tumor progression and evolution in KS.

PMID- 8879302
TI  - Subtle clues to the diagnosis of cholesterol embolism.

PMID- 8879301
TI  - Perianal basal cell carcinoma: a comparative histologic, immunohistochemical, and
      flow cytometric study with basaloid carcinoma of the anus.
AB  - Perianal basal cell carcinoma is a very rare tumor accounting for only 0.2% of
      the anorectal tumors. It must be distinguished from basaloid carcinoma of the
      anus, which resembles it histologically but shows a much more aggressive
      behavior, metastasizes early, and often proves fatal, thus requiring different
      therapy. Differential diagnosis of both entities by light microscopy may be
      difficult. Five cases of perianal basal cell carcinoma and five cases of basaloid
      carcinoma were studied by means of immunohistochemistry and flow cytometry. Some
      immunohistochemical markers, such as epithelial membrane antigen,
      carcinoembrionic antigen, and keratins, as well as the lectin Ulex europaeus
      agglutinin I stained basaloid carcinoma and were negative for basal cell
      carcinoma. In contrast, the monoclonal antibody Ber-EP4 seems to be a good marker
      for perianal basal cell carcinoma and useful in differentiating it from basaloid
      carcinoma of the anus. Basaloid carcinomas are associated with a significantly
      higher S-phase fraction than are perianal basal cell carcinomas (p < 0.01).

PMID- 8879303
TI  - Epidermotropically metastatic breast carcinomas. Rare histopathologic variants
      mimicking melanoma and Paget's disease.
AB  - Epidermotropic metastases from internal malignancies are exceedingly rare. We
      report two examples of epidermotropic metastatic breast carcinoma with striking
      intraepidermal involvement. The first case mimicked melanoma because the
      neoplastic cells contained melanin and were disposed both as single units and as
      nests at the dermoepidermal junction and throughout the epidermis. In the second
      case, the neoplastic cells were seen as isolated neoplastic cells with large,
      pale cytoplasm scattered throughout the epidermis, closely resembling
      extramammary Paget's disease. Immunohistochemical studies in both cases
      demonstrated the epithelial nature of intraepidermal neoplastic cells, which
      showed an immunophenotype identical to the neoplastic cells present in the
      dermis: positive staining with anti-cytokeratins, CEA, EMA, and GCDFP-15 and
      negative with anti-S-100 protein and HMB-45. These findings ruled out the
      possibility of a collision lesion, or simultaneous occurrence of melanoma and
      metastatic breast carcinoma. Pagetoid intraepidermal spread of metastatic breast
      carcinoma, as in our two cases, is exceptional. We also discuss the histogenetic
      similarities between our findings and those of mammary and extramammary Paget's
      disease, as well as the differential diagnosis of other cutaneous disorders
      characterized by pagetoid intraepidermal spread of neoplastic cells.

PMID- 8879304
TI  - Calciphylaxis with histologic changes of pseudoxanthoma elasticum.
AB  - Calciphylaxis is a rare condition of widespread calcification of tissues and
      blood vessels with accompanying vascular thrombosis and ischemic necrosis. Most
      cases develop in association with hyperparathyroidism in patients with chronic
      renal failure. Pseudoxanthoma elasticum (PXE) is a hereditary condition of
      abnormal elastic tissue structure that leads to widespread abnormalities of the
      skin, retina, and visceral organs. Histologic changes of PXE have been observed
      as coincidental findings in several conditions such as following trauma to the
      skin manifest as isolated plaques often in scars. We observed histologic findings
      of PXE in a patient with chronic renal failure who developed fatal calciphylaxis.
      Complete evaluation failed to reveal evidence of systemic findings of PXE.
      Histologic changes of PXE may be seen in patients with calciphylaxis as a
      coincidental finding. Rapidly developing soft tissue calcification may lead to
      the expression of the characteristic histopathologic findings of PXE without
      evidence of classic clinical manifestations of PXE. Calciphylaxis should be added
      to the list of disorders that may lead to microscopic PXE-like changes.

PMID- 8879305
TI  - Nodular myxoid change in melanocytic nevi. A report of two cases.
AB  - Mucin deposition has been reported in a variety of cutaneous neoplasms, including
      melanocytic nevi. We describe a series of melanocytic nevi with nodular myxoid
      change.

PMID- 8879307
TI  - Pleomorphic angioleiomyoma.
AB  - A 72-year-old man presented with a single nodule in the right thigh of 12 years'
      evolution. Histopathology confirmed the diagnosis of angioleiomyoma. However,
      unlike other tumors of this type reported in the literature, marked nuclear
      pleomorphism without mitotic figures was noted.

PMID- 8879306
TI  - Giant cell fibroblastoma. New histological observations.
AB  - Giant cell fibroblastoma is a rare mesenchymal neoplasm of unknown origin and
      uncertain clinical course. The neoplasm has been considered by some authors as a
      juvenile variant of dermatofibrosarcoma protuberans. We report a patient with
      giant cell fibroblastoma, now 28 months following surgical removal, in which the
      neoplasm was characterized histologically by a proliferation of spindle-shaped
      cells intermixed with pseudovascular channels called "angiectoid spaces." The
      spaces were lined by large cells with pleomorphic nuclei intermixed with
      multinucleated cells. Immunohistochemically, the tumor stained diffusely for
      vimentin and CD34, a surface glycoprotein expressed by some mesenchymal neoplasms
      including dermatofibrosarcoma protuberans. We postulate a mechanism of formation
      of the angiectoid spaces based on histopathological findings in serially
      sectioned portions of the neoplasm. Positive staining of tumor cells for CD34
      supports a possible relationship of the neoplasms with dermatofibrosarcoma
      protuberans.

PMID- 8879308
TI  - Idiopathic palmoplantar hidradenitis.
AB  - Idiopathic plantar hidradenitis (IPH) is a recently described condition primarily
      affecting healthy children who develop tender lesions localized to the plantar or
      lateral aspects of the feet with histologic findings similar to those seen in
      neutrophilic eccrine hidradenitis (NEH), although with certain notable exceptions
      including the absence of syringosquamous metaplasia and the presence, in most
      cases, of neutrophilic abscesses adjacent to eccrine coils. Since its original
      description, three additional patients have been reported, one with palmoplantar
      lesions, extending the disease's clinical spectrum to include palmar as well as
      plantar surfaces. We report on a healthy 8-year-old girl with tender,
      erythematous nodules on palms and soles and review the literature on this
      subject.

PMID- 8879309
TI  - Unilateral areolar sebaceous hyperplasia in a male.
AB  - We report a case of areolar sebaceous hyperplasia involving the right mammary
      areola in a 49-year-old male. Areolar sebaceous hyperplasia, an uncommon entity
      first described by Catalano and Ioannides in 1985, is characterized clinically by
      yellowish thickening of the areolae and histopathologically by large numbers of
      mature hyperplastic sebaceous lobules connected to the skin surface through
      short, hairless infundibular canals. Since its original description, only two
      additional reports have been published. To our knowledge, our patient is the
      first reported of areolar sebaceous hyperplasia in a male.

PMID- 8879310
TI  - Nevus sebaceus with apocrine and sebaceous differentiation.
AB  - A case of nevus sebaceus associated with an unusual epithelial proliferation
      demonstrating apocrine and sebaceous differentiation and not conforming to known
      cutaneous or skin adnexal neoplasms is reported.

PMID- 8879311
TI  - Lymphoepithelial cyst associated with epithelial inclusion cyst.
AB  - Lymphoepithelial cyst of the oral cavity is an uncommon cystic lesion lined with
      stratified squamous epithelium surrounded by lymphoid tissue. We report a case of
      lymphoepithelial cyst associated with two large epithelial inclusion cysts.

PMID- 8879312
TI  - Medical epics.

PMID- 8879313
TI  - Glomus tumor in neural tissue.

PMID- 8879314
TI  - New products and research bring guarded optimism, new questions about AIDS
      therapy.

PMID- 8879315
TI  - Nonnucleoside reverse transcriptase inhibitor marketed for AIDS therapy.

PMID- 8879317
TI  - Most hospitals have managed care arrangements.

PMID- 8879316
TI  - Revised performance measures for managed care plans released.

PMID- 8879318
TI  - Pharmacy directors, employers paint picture of HMO pharmacy benefit.

PMID- 8879319
TI  - Managed care statistics from trade association, Hoechst show growth of Medicare
      and Medicaid enrollment.

PMID- 8879320
TI  - Overall savings from hospice care appear small.

PMID- 8879321
TI  - Determining the compensation status--salaried or nonsalaried--of pharmacists.

PMID- 8879322
TI  - Uremic pruritus.
AB  - Uremic pruritus and its treatment are reviewed. Pruritus affects 50-90% of
      patients undergoing peritoneal dialysis or hemodialysis; symptoms usually begin
      about six months after the start of dialysis and range from localized and mild to
      generalized and severe. The mechanism underlying uremic pruritus is poorly
      understood; possibilities include secondary hyperparathyroidism and divalent-ion
      abnormalities; histamine, allergic sensitization, and proliferation of skin mast
      cells; hypervitaminosis A; iron-deficiency anemia; neuropathy and neurologic
      changes; or some combination of these. The cornerstone of therapy for uremic
      pruritus is regular, intensive, efficient dialysis. Other nonpharmacologic
      measures consist of the use of non-complement-activating dialysis membranes,
      compliance with dietary restrictions, electric-needle (acupuncture) therapy, and
      ultraviolet light therapy. Pharmacologic treatments that have been used include
      activated charcoal, antihistamines, capsaicin, cholestyramine, emollients and
      topical corticosteroids, epoetin, pizotyline, ketotifen, and nicergoline.
      Treatment results have been highly variable, and many of the clinical trials have
      been flawed. Phosphate-binding agents appear to be the most effective. Although
      enough is known to determine a reasonable set of steps in approaching a patient's
      uremic pruritus, more research is needed to understand the pathophysiology of
      this condition and to establish more reliable treatments. Pruritus is a common
      and sometimes severe complication of chronic renal failure. Efficient dialysis,
      dietary restrictions, phosphate-binding therapy, and phototherapy are the most
      effective treatments currently available.

PMID- 8879323
TI  - Quality of pharmacists' documentations in patients' medical records.
AB  - Training pharmacists to appropriately document patient-specific problems and
      recommendations in patients' medical records and subsequent monitoring of
      pharmacist-written documentation are described. The medical staff of a tertiary
      care teaching hospital recommended that pharmacists be allowed to write in the
      permanent portion of patients' medical records. A six-month pilot program was
      approved to train pharmacists in writing chart notes. Notes would be assessed
      according to the following criteria: necessity (i.e., a chart note was the
      appropriate means of communication), clarity, legibility, completeness, correct
      format, and lack of judgmental language. Initial training was by physicians from
      the pharmacy and therapeutics committee, with more extensive training by a
      committee composed of clinical and administrative pharmacists. After training
      ended, each pharmacist's first few notes were reviewed by a member of the
      pharmacy committee. The quality of pharmacist-written notes is reviewed
      quarterly. The first quarterly evaluation and another review 1 1/2 years later
      showed that all pharmacist notes met all of the established criteria. A
      multidisciplinary approach was effective in training pharmacists to document
      interventions appropriately in patients' permanent records. Ongoing monitoring
      ensures the continuing quality of such documentation.

PMID- 8879324
TI  - Outsourcing the preparation of parenteral nutrient solutions.
AB  - A hospital pharmacy's experience with using an outsourcing center to prepare
      parenteral nutrient solutions (PNs) is described. In 1994 the pharmacy at a 340
      bed level 1 trauma center selected an outsourcing center located 20 miles away to
      provide PN-compounding services; the center is licensed as a manufacturer and has
      an extensive quality control program. The necessary telephone and computer links
      were established. When a PN order is received, the pharmacist simply dials into
      the outsourcing computer system and enters the order. At 1400, a pharmacist dials
      into the system to verify all PN orders entered for that day. After 1500,
      personnel at the outsourcing center print labels and compound the solutions,
      which are delivered by courier within a few hours. The net savings during the
      first year of outsourcing PNs were estimated at about $59,000. The savings were
      attributable to the elimination of a technician full-time equivalent (FTE), a
      reduction in pharmacist labor, and favorable contract provisions; money was saved
      even though the service's PN-preparation fees outweighed the savings from
      reductions in labor. The hospital's onsite inventory of PN supplies decreased by
      $5800, and storage space was freed for other uses. Very few problems were
      associated with the service provided. Outsourcing the preparation of parenteral
      nutrient solutions reduced personnel, inventory, and expenditures in a hospital
      pharmacy.

PMID- 8879325
TI  - Stability of baclofen, captopril, diltiazem hydrochloride, dipyridamole, and
      flecainide acetate in extemporaneously compounded oral liquids.
AB  - The stability of drugs commonly prescribed for use in oral liquid dosage forms
      but not commercially available as such was studied. Baclofen 10 mg/mL, captopril
      0.75 mg/mL, diltiazem hydrochloride 12 mg/mL, dipyridamole 10 mg/mL, and
      flecainide acetate 20 mg/mL were prepared in a 1:1 mixture of Ora-Sweet and Ora
      Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock
      Laboratories), and cherry syrup and placed in 120-mL amber, clear polyethylene
      terephthalate bottles. The source of all the drugs was tablets. Six bottles were
      prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C,
      all in the dark. A sample was removed from each bottle immediately after
      preparation and at various intervals up to 60 days and analyzed for drug
      concentration by stability-indicating high-performance liquid chromatography. A
      mean of at least 92% of the initial drug concentration was retained for up to 60
      days in the baclofen, diltiazem hydrochloride, dipyridamole, and flecainide
      acetate liquids at both 5 and 25 degrees C. There were no substantial changes in
      the appearance or odor of any of the liquids or in the pH. Baclofen 10 mg/mL,
      diltiazem hydrochloride 12 mg/mL, dipyridamole 10 mg/mL, and flecainide acetate
      20 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three
      extemporaneously compounded oral liquids.

PMID- 8879327
TI  - Gentamicin pharmacokinetics in Native Americans of Apache ancestry.

PMID- 8879326
TI  - Compatibility of cefmetazole sodium with commonly used drugs during Y-site
      delivery.
AB  - The compatibility of cefmetazole sodium and selected other drugs during Y-site
      delivery was evaluated. Cefmetazole 100 mg/mL (as the sodium salt) in sterile
      water for injection and each of 34 drugs or solutions commonly used with it were
      mixed together by Y-site injection. Secondary drugs were administered at selected
      concentrations and rates and delivered by the method (i.v. push, i.v. infusion,
      or syringe pump) commonly used for the drug at the institution where the study
      was done. Each injection set included a filter system with a 0.8-micron filter
      disk. Tests were done in triplicate. After each test, the Y injection site and
      the tubing after it were visually inspected for precipitate and color change. If
      no particles or color change was detected, the filter disk was observed under a
      microscope. Drugs were deemed compatible with cefmetazole if unaided observation
      detected no color change or particles and the number of particles detected by
      microscopic examination was below that specified in USP guidelines. A precipitate
      formed when cefmetazole sodium mixed with diphenhydramine hydrochloride,
      droperidol, erythromycin (50 mg/mL, as the lactobionate), haloperidol lactate,
      prochlorperazine edisylate, promethazine hydrochloride, or vancomycin (50 mg/mL,
      as the hydrochloride salt). No particles or color change was detected by unaided
      observation of mixtures containing dobutamine or erythromycin 10 mg/mL, but the
      number of particles detected by microscopic examination exceeded USP limits. All
      other drugs tested were compatible with cefmetazole. Cefmetazole 100 mg/mL (as
      the sodium salt) in sterile water for injection was shown to be compatible with
      25 of 34 tested drug solutions during Y-site delivery.

PMID- 8879328
TI  - Clinical and economic effects of replacing enalapril with benazepril in
      hypertensive patients.

PMID- 8879329
TI  - Staff development program for identifying and resolving drug therapy problems.

PMID- 8879330
TI  - Effect of constructive feedback on pharmacist handling of orders for monitored
      antimicrobials.

PMID- 8879331
TI  - Pharmaceutical services at the 1995 Special Olympics World Games.

PMID- 8879332
TI  - Drug formularies provide a path to best care.

PMID- 8879333
TI  - Unintended consequences of drug formularies.

PMID- 8879334
TI  - Considerations in the formulary selection of hydroxymethylglutaryl-coenzyme A
      reductase inhibitors.

PMID- 8879335
TI  - Lack of clinical evidence for potential interaction between isoniazid and
      selective serotonin-reuptake inhibitors.

PMID- 8879336
TI  - No basis for associating nonprescription ibuprofen and similar agents with
      necrotizing fasciitis.

PMID- 8879337
TI  - Extemporaneous preparation of an injection is issue of quality, not ethics.

PMID- 8879338
TI  - Disagreement with ethics discussion of pharmacist error.

PMID- 8879339
TI  - Effect of 14 years of antihypertensive treatment on renal function and urinary
      albumin excretion in primary hypertension.
AB  - The effects on blood pressure (BP), renal function, and urinary albumin excretion
      (UAE) of 14 years of antihypertensive treatment were studied and compared to the
      changes seen with normal aging. The studied groups included randomly selected men
      with newly diagnosed primary hypertension at baseline (n = 23) and normotensive
      (NT) men of the same age (n = 11). The hypertensives (HT) were treated with beta
      blockers either as monotherapy or combined with diuretics or hydralazine.
      Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF, para
      aminohippurate clearance), renal vascular resistance (RVR), and 24-h UAE were
      determined. The two groups were investigated at baseline (before treatment) and
      after 7 and 14 years. At baseline, BP and RVR were significantly increased and
      RBF was significantly decreased in the HT over that in the NT. The BP in the HT
      was significantly reduced after 7 years of treatment and a further but
      nonsignificant reduction to 139 +/- 14/88 +/- 6 mm Hg (mean +/- SD) was seen
      after 14 years. GFR in the HT was significantly reduced from 103 +/- 15 mL/min to
      84 +/- 19 mL/min (mean +/- SD) after 7 years, but no further reduction was seen
      after 14 years. During the 14 years RBF decreased and RVR increased in the HT but
      these changes were of the same magnitude as in the NT. The UAE did not change
      significantly during the study. In conclusion, good blood pressure control with
      conventional antihypertensive treatment in mild to moderate primary hypertension
      seems to protect the kidney from progressive decline in GFR and increase in UAE.
      The increase in RVR and the decrease in RBF seen during 14 years of
      antihypertensive treatment was of the same magnitude as that seen with normal
      aging.

PMID- 8879340
TI  - Long-term renal preservation in essential hypertension. Angiotensin converting
      enzyme inhibition is superior to beta-blockade.
AB  - Antihypertensive treatment is known to slow down the decline in glomerular
      filtration rate (GFR) with time. Angiotensin converting enzyme (ACE) inhibition
      has been shown to be more effective in this regard than conventional
      antihypertensive therapy. In a recent prospective, randomized, double blind trial
      in 257 patients with essential hypertension, the loss of GFR, determined with
      51Cr-EDTA clearance, was significantly less with an ACE inhibitor (cilazapril)
      than with a beta-adrenoceptor blocker (atenolol) during the first year of
      treatment. However, after 2 years, the two therapies were equally effective in
      this regard, thereby creating doubts about the long-term superiority of ACE
      inhibition in this regard. In order to elucidate whether the superior renal
      preservation with the ACE inhibitor was a transient effect, GFR was measured
      after 1 more year of treatment, i.e., after 36 months. At that time, the decline
      in GFR was significantly smaller in the ACE inhibitor group as compared to the
      beta-adrenoceptor blocker group (-3.0 [-5.5, -1.0; 95% CI] v -7.0 [-9.0, -4.5;
      95% CI] mL/min x 1.73 m2; P = .026). This demonstrates that in the treatment of
      essential hypertension ACE inhibition preserves GFR significantly better than
      beta-adrenoceptor blockade during long-term therapy.

PMID- 8879341
TI  - Antihypertensive therapy and quality of life. Influence of blood pressure
      reduction, adverse events, and prior antihypertensive therapy.
AB  - Quality of life is an important attribute of antihypertensive therapy. Previous
      studies have not addressed the importance of a patient's prior pharmacotherapy on
      quality of life, which may serve as the basis of reference for a new therapy. Nor
      have previous studies compared commonly used quality of life instruments for
      consistency, or investigated whether improvement or worsening of quality of life
      correlates with adverse events or blood pressure reduction. Two hundred eighteen
      hypertensive patients with diastolic blood pressure (95 to 114 mm Hg) after a 4-
      to 5-week placebo washout period were enrolled in a randomized double-blind,
      parallel group dose-escalation trial to compare the effects of amlodipine (2.5 to
      10 mg), bisoprolol (2.5 to 10 mg)/hydrochlorothiazide (HCTZ) 6.25, and enalapril
      (5 to 20 mg) on blood pressure, adverse events, and quality of life. Three
      quality of life instruments (General Well-Being Index, Vital Signs Quality of
      Life, Zung Self-Rating Depression Scale) were administered during original
      therapy, after placebo washout, and after 12 weeks of optimally titrated clinical
      trial pharmacotherapy. Our results demonstrated that removal from prior therapy
      had no detectable influence on subsequent evaluation of quality of life. The
      three quality of life instruments were consistent with the changes observed with
      the three therapies: a trend toward better quality of life with amlodipine and
      bisoprolol/HCTZ. Adverse events, but not systolic or diastolic blood pressure
      reduction correlated directly with changes in quality of life.

PMID- 8879342
TI  - Interactive effects of insulin with dihydrotestosterone on adrenergic tone in
      isolated rat tail arterial rings.
AB  - Reversal of sex-related differences in incidence of vascular diseases in Type II
      diabetics suggests that high circulating insulin may reverse normal differences
      in vascular actions of sex steroids. We have found that a high concentration of
      insulin can reverse small inhibitory actions of low estradiol on adrenergic tone
      in isolated arterial rings. Thus, we measured effects of high insulin on actions
      of dihydrotestosterone on adrenergic tone and specificity of these effects with
      respect to time of exposure to the steroid and its concentration. In the first of
      two studies, tail arterial rings from 16 male rats were incubated for 2 h with
      either dihydrotestosterone (0.0012 mumol/ L), insulin (0.5 mU/mL),
      dihydrotestosterone plus insulin, or vehicles. Rings were then contracted with
      norepinephrine administered cumulatively from 10(-9) to 10(-4) mol/L. Contractile
      responses to norepinephrine from 10(-7) to 10(-4) mol/L were increased by
      dihydrotestosterone in the absence (P < .05) but not in the presence of insulin.
      Also, norepinephrine's EC50 was reduced by dihydrotestosterone in the absence (P
      < .05) but not in the presence of insulin. In a second study (with rings from 12
      more rats), the same low level of dihydrotestosterone failed to affect
      norepinephrine contractions acutely (that is, within 6 min), whereas much higher
      levels (12 and 120 mumol/L) rapidly inhibited the same contractions, independent
      of 2-h preincubation with insulin. Thus, prolonged exposure to a low
      physiological level of dihydrotestosterone enhances adrenergic tone, whereas
      acute exposure to high levels inhibits it. In addition, a high level of insulin
      specifically blunts the delayed enhancing effect of the low dihydrotestosterone.
      These results suggest possible mechanisms underlying sex-related differences in
      arterial vascular tone and the potential impact of hyperinsulinemia on such
      differences.

PMID- 8879343
TI  - Inducible nitric oxide synthase in vascular smooth muscle cells from
      prehypertensive spontaneously hypertensive rats.
AB  - The inducible nitric oxide synthase (iNOS) present in vascular smooth muscle
      cells (VSMC) may play a role in the generation of nitric oxide (NO) in the
      vascular wall, regulating blood vessel tone in normotension and hypertension. In
      this study the effect of interleukin (IL)-1 beta, a cytokine that induces iNOS,
      on NO generation (measured as nitrite), cyclic guanosine monophosphate (cGMP)
      generation, and steady-state abundance of iNOS mRNA were examined in VSMC from 3
      week old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats,
      during the period preceding the elevation of blood pressure. With cell density
      dependent variations in nitrite production eliminated, VSMC from SHR and WKY did
      not differ in NO generation except after prolonged incubation (30 h), when SHR
      cells produced less NO. However, cGMP concentrations associated with IL-1 beta
      stimulation were significantly smaller in SHR VSMC than in cells from WKY. IL-1
      beta stimulation resulted in increased abundance of iNOS mRNA to the same extent
      in both WKY and SHR VSMC. Inhibitors of NOS, NG-monomethyl-L-arginine (L-NMMA)
      and N omega-nitro-L-arginine methyl ester (L-NAME), did not block the induction
      of iNOS mRNA, although nitrite production and cGMP generation were inhibited. The
      protein synthesis inhibitor cycloheximide and the RNA synthesis inhibitor
      actinomycin-D almost completely blocked the production of nitrite in cells from
      both strains of rats. Actinomycin-D completely blocked the induction of iNOS mRNA
      by IL-1 beta in cells from both strains of rats, whereas cycloheximide partially
      blocked its synthesis in WKY, but had no significant effect on IL-1 beta induced
      expression of iNOS mRNA in SHR VSMC. Thus, IL-1 beta controls iNOS gene
      expression at the transcriptional level, and an intermediate labile protein,
      whose synthesis is inhibited by cycloheximide, is required for IL-1 beta
      stimulated induction of iNOS mRNA transcription in WKY cells but not in SHR. We
      conclude that although iNOS is expressed to similar extent in VSMC of
      prehypertensive SHR and WKY and similar amounts of NO are initially generated,
      there are differences between the VSMC of SHR and WKY in the regulation of the
      transcription of iNOS mRNA, there is a lower sustained production of NO, and
      there is a reduced generation of cGMP in response to IL-1 beta stimulated NO
      production. These differences between VSMC from prehypertensive SHR and WKY may
      indicate a pathophysiological role of iNOS in early blood pressure elevation in
      SHR.

PMID- 8879344
TI  - Age-related changes in interstitial norepinephrine. A microdialysis study in
      spontaneously hypertensive rats.
AB  - This study was aimed at evaluating the time course of interstitial norepinephrine
      (NE) concentrations in the white adipose tissue and at assessing NE release after
      local perfusion with tyramine hydrochloride (TYR) in rats of different ages. Two
      groups of eight spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto
      (WKY) rats, aged 14 to 16 weeks, were studied. The same animals were reexamined
      at the age of 52 to 54 weeks. A soft microdialysis probe was implanted
      subcutaneously in the parascapular region and was perfused with Ringer solution
      (flow rate: 2.0 microL/min). After an equilibration period, NE levels were
      monitored for 120 min, following which, TYR (0.1 nmol/min) was perfused for 90
      min. Dialysates from each 30 min collection period were analyzed by HPLC using
      electrochemical detection. At 14 to 16 weeks, SHR showed higher NE concentrations
      in dialysates as compared to WKY (1124.0 pg/mL v 541.4 pg/mL; P < .001) and a
      blunted response to TYR challenge. The net output, estimated by subtracting basal
      values, was 86.0 pg NE/h in SHR as compared to 212.5 pg NE/ h in WKY (P = .005).
      Differences in basal NE levels persisted in the same aged groups (P < .001) as
      well as a blunted response to TYR. The net NE output was still lower in SHR as
      compared to WKY (320.4 pg NE/h v 414.7 pg NE/h in WKY; P = .023). Basal levels of
      NE in SHR could be accounted for by either a higher amount of the
      neurotransmitter stored into and released from vescicles or by an increased
      firing rate of the sympathetic fibers. Since TYR is known to deplete axoplasmic
      but not vesicular NE available for neurotransmission, the response of SHR to TYR
      challenge is consistent with an increased turnover rate of NE. Aging was
      associated with an increased response to TYR in both strains, thus suggesting an
      age-dependent decline in turnover rates or changes in NE reuptake mechanisms.

PMID- 8879345
TI  - Comparison of K+ channel properties in freshly isolated myocytes from thoracic
      aorta of WKY and SHR.
AB  - Altered function of smooth muscle cell K+ channels have been reported in
      hypertension, but the contribution of various K+ channel types to these changes
      has not been completely determined. The purpose of this study was to compare the
      contribution of K+ channel types to whole cell K+ currents recorded from isolated
      thoracic aorta myocytes of 13 to 15 week old Wistar-Kyoto (WKY) and spontaneously
      hypertensive rats (SHR). Cells were isolated by collagenase and elastase
      digestion, and K+ currents recorded using whole cell voltage clamp methods at
      room temperature. Cells were superfused with a solution containing (in mmol/ L)
      140 NaCl, 5 KCl, 2 CaCl2, 1 MgCl2, 10 HEPES, and 10 glucose. Pipettes were filled
      with a solution containing (in mmol/L) 120 KCl, 5 NaCl, 5 MgATP, 20 HEPES, and 10
      BAPTA. The K+ currents (IK) recorded from a holding potential (HP) of -80 mV were
      smaller in the SHR compared to those in WKY (for example, at 20 mV: WKY = 6.1 +/-
      0.6 pA/pF and SHR = 3.7 +/- 0.2 pA/pF). Values of cell capacitance were not
      different between the two groups (WKY = 25.2 +/- 3.2 pF and SHR = 26.6 +/- 1.9
      pF). A component of IK inhibited by voltage (Kv) over the range from -80 to -20
      mV was smaller in SHR. The voltage dependence of Kv availability and activation
      were not significantly different between the two groups. IK recorded from a HP = 
      20 mV (KCa) was not different between the two groups. Difference currents
      calculated from IK measured at HP of -80 and -20 mV (that is, Kv) were smaller in
      SHR as was the fraction of IK inhibited by 4-aminopyridine. These results suggest
      that under conditions of low intracellular [Ca2+] there are no differences in KCa
      currents, but the Kv currents are smaller in SHR. Inhibition of Kv by 4
      aminopyridine (0.1 to 10 mmol/L) caused larger increases in basal tone in WKY
      aorta. These results suggest that Kv channels contribute to resting K+
      conductance in both WKY and SHR aorta, but with a relatively larger contribution
      in the WKY.

PMID- 8879346
TI  - Vascular hypertrophy and albumin permeability in a rat model combining
      hypertension and diabetes mellitus. Effects of calcium antagonism, angiotensin
      converting enzyme inhibition, and angiotensin II-AT1-receptor blockade.
AB  - The aim of this study was to compare the effects of angiotensin converting enzyme
      (ACE) inhibition, angiotensin II (AII) AT1-receptor blockade, and dihydropyridine
      calcium antagonism on hypertrophy and on vascular albumin permeability in kidney,
      heart, and mesenteric artery in a model combining genetic hypertension and
      diabetes mellitus. Diabetes mellitus was induced by streptozotocin in 8-week-old
      spontaneously hypertensive rats. The animals were randomized to receive no
      treatment, the angiotensin converting enzyme inhibitor ramipril, the AII AT1
      receptor blocker valsartan, or the dihydropyridine calcium antagonist lacidipine
      for 3 weeks. Vascular albumin permeability was measured as the tissue content of
      intravenously injected Evans blue dye (EB) in kidney, heart, and mesenteric
      artery and the tissue/plasma EB ratio was calculated. Systolic blood pressure was
      reduced by all three antihypertensive regimens. Glycemic control was similar in
      all diabetic groups. Kidney hypertrophy was not affected by any of the
      antihypertensive drugs. Hypertrophy of the mesenteric artery was enhanced by
      lacidipine but was not affected by ramipril or valsartan. Relative heart weight
      was also increased by lacidipine. Vascular albumin permeability, expressed as EB
      content in micrograms/gram dry weight or as tissue/plasma EB ratio, was higher in
      the kidneys of lacidipine-treated rats than in any other group of diabetic rats.
      There was a positive correlation between kidney weight/body weight and
      kidney/plasma EB ratio in the diabetic rats. These findings indicate that the
      dihydropyridine calcium antagonist lacidipine is associated with an unfavorable
      effect on vascular hypertrophy and on vascular albumin permeability in the
      kidneys in rats with hypertension and diabetes mellitus. Furthermore, there seems
      to be a coupling in the diabetic kidney between hypertrophy and increased
      vascular albumin permeability.

PMID- 8879347
TI  - Effects of low-dose epinephrine infusion on cardiovascular and renal responses to
      water immersion in humans.
AB  - Elevated plasma epinephrine concentrations may impair blood pressure homeostasis
      and renal sodium and volume excretion in response to central hypervolemia. We
      studied the effects of a low-dose epinephrine infusion (12 ng/kg/min) on
      cardiovascular and renal responses to a thermoneutral head-out water immersion in
      eleven healthy men. Responses to water immersion without epinephrine were
      characterized by significant suppression of plasma renin activity (PRA), plasma
      aldosterone concentration, and renal norepinephrine excretion, and an
      augmentation of natriuresis and diuresis. Epinephrine infusion, which raised mean
      plasma epinephrine concentration 4.3-fold, slightly increased plasma
      norepinephrine and renal norepinephrine excretion, markedly stimulated PRA
      (+66.7%), but decreased plasma aldosterone (-11.7%), and augmented renal sodium
      and volume excretion. Despite the presence of the epinephrine infusion, water
      immersion continued both to suppress PRA and aldosterone, and to increase
      natriuresis and diuresis in a qualitatively similar pattern. During all
      conditions blood pressure and heart rate remained unchanged. It is concluded that
      physiologic responses to central hypervolemia are not impaired at stress levels
      of circulating epinephrine. During epinephrine infusion, despite a concomitant
      increase in plasma norepinephrine and a stimulation of PRA, blood pressure
      remained constant in response to water immersion due to an augmentation of
      natriuresis and diuresis.

PMID- 8879348
TI  - Enalapril does not improve left ventricular diastolic dysfunction in young and
      mild hypertensives without concomitant hypertrophy.
AB  - The aim of the study was to determine whether enalapril monotherapy can improve
      left ventricular diastolic dysfunction (LVDD) in young and mild hypertensive
      patients without concomitant left ventricular hypertrophy (LVH). Fifty patients
      with hypertension < or = 160/100 mm Hg, aged < or = 50 years, normal two
      dimensional echocardiographic (2-D echo) measurements, and LVDD were enrolled in
      this study. The LVDD was defined as a transmitral early (E) to atrial (A) peak
      velocity ratio of < or = 1. The mean documented hypertension was 6.3 years. The
      mean daily dose of enalapril was 13 mg. Baseline and 24-month follow-up
      echocardiograms were evaluated. Thirty-eight age- and sex-matched healthy
      subjects served to establish the normal reference values of 2-D echo
      measurements. After treatment, peak early diastolic velocity (E) (49 +/- 6 cm/sec
      v 48 +/- 10 cm/sec; P = not significant), peak atrial velocity (A) (62 +/- 9
      cm/sec v 62 +/- 10 cm/sec; P = not significant), and E/A ratio (0.80 +/- 0.10 v
      0.78 +/- 0.13; P = not significant) remained unchanged. Moreover, early to atrial
      velocity-time integral ratio (1.24 +/- 0.08 v 1.23 +/- 0.11; P = not significant)
      did not change. The left ventricular mass index, relative wall thickness, left
      ventricular end-systolic diameter, left atrial diameter, fractional shortening,
      heart rate, and body mass index did not show significant changes in all
      hypertensive patients. In conclusion, long-term antihypertensive therapy with
      enalapril did not lead to an improvement of LVDD in young and mild hypertension
      patients without concomitant LVH.

PMID- 8879349
TI  - Lack of independent relationships between left ventricular mass and
      cardiovascular reactivity to physical and psychological stress in the Coronary
      Artery Risk Development in Young Adults (CARDIA) Study.
AB  - The objective of this study was to determine whether exaggerated blood pressure
      (BP) reactivity to stress and psychosocial characteristics are related to left
      ventricular mass (LVM) in a large cohort of young adults. Analyses were conducted
      with 3,742 participants of the CARDIA study (945 white men, 1,024 white women,
      781 black men, and 992 black women), evaluated in 1990 to 1091 with
      echocardiographic measurement of LVM. Analyses were stratified by gender and
      race. The relationships of LVM/height2.7 and cardiovascular reactivity to
      physical and psychological stressors (treadmill exercise, cold pressor, video
      game, and star-tracing tasks), were examined in both univariate and multivariate
      analyses adjusting for baseline BP, weight, and other relevant biobehavioral
      variables. The relationships between LVM and several psychosocial characteristics
      (hostility, anger suppression, anxiety, depressive symptoms, and education) were
      also assessed. Systolic blood pressure (SBP) reactivity to exercise was
      significantly related to LVM in black and white men; LVM was 10% greater among
      white men with exaggerated (upper quintile) peak exercise SBP than among other
      white men. SBP reactivity to the cold pressor test was related to LVM in all
      race/gender groups, although the relationship remained significant only among
      white men and women in the multivariate analysis. Diastolic blood pressure (DBP)
      reactivity to the video game was related to LVM only among black men in adjusted
      analyses. After adjusting for resting BP, weight, and other covariates in linear
      multiple regression models, SBP reactivity to exercise explained only 3% of the
      variance in LVM among white men. Otherwise, reactivity to other stressors or
      psychosocial variables accounted for no more than 1% of the variance in LVM. It
      was concluded that among a cohort of young adults, blood pressure reactivity to
      physical and mental stressors did not add substantially to the prediction of LVM
      when resting BP, weight, and other covariates were taken into account.

PMID- 8879350
TI  - Production of C-type natriuretic peptide in human aortic endothelial cells
      induced by activation of protein kinase C.
AB  - The effects of activators and inhibitors of protein kinase C (PKC) on the
      production of C-type natriuretic peptide (CNP) by cultured human aortic
      endothelial cells were examined. The PKC activators phorbol 12-myristate 13
      acetate (PMA) and 1-oleoyl 2-acetyl glycerol (OAG) stimulated CNP release; the
      maximal effects were apparent at 4 h, at which time release was 934 and 205% of
      the control value, respectively. The PKC inhibitors staurosporine and H-7 did not
      affect basal CNP release, but each abolished the increase in CNP release induced
      by PMA or OAG. PKC was activated and translocated from cytosolic to membrane
      fractions in endothelial cells exposed to PMA or OAG; the maximal effect was
      apparent at 1 h. PMA and OAG each increased the abundance of CNP mRNA, with the
      maximal effect at 2 h. These data suggest that activation of PKC by PMA or OAG
      results in an increase in the abundance of CNP mRNA and subsequent enhancement of
      CNP production and release in human aortic endothelial cells.

PMID- 8879351
TI  - Modulation of ANF-R2/ANP-C receptors by angiotensin II in vascular smooth muscle
      cells.
AB  - In the present studies, we have investigated the modulation of atrial natriuretic
      factor (ANF) receptor of R2 subtype (ANF-R2) coupled to adenylyl cyclase/cAMP
      signal transduction system by angiotensin II (AII). C-ANF4-23 [C-ANF4-23,
      [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANF4-23-NH2] and AII inhibited adenylyl
      cyclase activity in control vascular smooth muscle cells (VSMC A-10) by about 40%
      and 30% respectively. Pretreatment of the cells with AII resulted in the
      attenuation of both C-ANF4-23- and AII-mediated inhibition of adenylyl cyclase.
      Losartan treatment of the cells was able to partially block (approximately 50%)
      the AII- as well as C-ANF4-23-mediated inhibitions of adenylyl cyclase that are
      completely lost by AII pretreatment. The pretreatment of the cells with AII alone
      or with losartan did not affect the [125I]-ANF binding to ANF receptors. However,
      AII treatment resulted in the augmentation of the levels of Gi alpha 2 and Gi
      alpha 3. On the other hand, staurosporine (a protein kinase C [PKC] inhibitor)
      treatment of cells before AII treatment was able to prevent the attenuation of
      both C-ANF4-23 as well as AII-mediated inhibition of adenylyl cyclase elicited by
      AII. These results indicate that the AII modulation of ANF-R2 receptor-mediated
      inhibition of adenylyl cyclase is independent of ANF-R2 receptor density or the
      levels of Gi regulatory protein and may be due to the uncoupling of the ANF-R2
      receptor from the Gi protein. This uncoupling may be associated with the
      phosphorylation of the Gi protein by PKC activated by AII.

PMID- 8879352
TI  - Elevated endothelin-1 levels and persistent stage IV hypertension in a nonvolume
      overloaded anephric patient.
AB  - Persistent hypertension after nephrectomy is in most cases due to increased fluid
      volume. Endothelin-1 is a potent endogenous vasoconstrictor peptide. Its role in
      the development and maintenance of hypertension is not completely understood, but
      it might be significant in some cases. We report a case of stage IV hypertension
      after nephrectomy with elevated endothelin-1 levels and no volume overload.

PMID- 8879353
TI  - Systolic hypertension and the white coat phenomenon.

PMID- 8879354
TI  - Why study blood pressure reactivity to stress?

PMID- 8879355
TI  - Microbeads, magnets, and magic: the enchanting science of immunochemistry.

PMID- 8879356
TI  - Complications of disease and therapy: a comparison of younger and older patients
      with Parkinson's disease.
AB  - The incidence of complications associated with disease and treatment was compared
      in younger versus elderly patients with Parkinson's disease (PD). One hundred
      sixty-five patient records were divided according to patient age into two groups
      ("younger," 41 to 64, and "elderly," > or = 65 years) and reviewed for the
      incidence of dyskinesias, fluctuations, freezing, psychosis, dementia,
      depression, and insomnia. Younger patients had a greater incidence of chorea
      (75.8 percent vs 49.5 percent), dystonia (82.3 percent vs 49.0 percent),
      fluctuations (90.1 percent vs 68.1 percent), depression (73.2 percent vs 36.8
      percent), and insomnia (57.9 percent vs 18.1 percent). There were no significant
      differences in the incidence of freezing, dementia, or psychosis. At the time of
      the first adverse event, there was no difference in patient characteristics such
      as gender, lag time from disease diagnosis to levodopa initiation, disease
      symptoms at the time of diagnosis, levodopa dose, or concomitant drug use despite
      the fact that the older group had a longer duration of disease, higher Hoehn and
      Yahr stage, an older age at onset of PD, and longer duration of levodopa use.
      Younger patients with PD experience a greater incidence of adverse effects than
      do elderly PD patients. The spectrum of adverse effects is comparable to those of
      young-onset (< or = 40 years) patients.

PMID- 8879357
TI  - Clinical and research issues in breast cancer genetics.
AB  - Breast cancer is the most common form of cancer in women in the U.S. The risk
      factors for developing breast cancer include increasing age, a family history of
      breast cancer, and the lack of a child by age 30. A substantial fraction of
      breast cancer, however, occurs in women who have no identifiable risk factors.
      The diagnosis, pathology, treatment, and presymptomatic testing of cancer
      susceptibility genes are reviewed. Syndromes with an associated risk of breast
      cancer are described, such as hereditary breast-ovarian cancer syndrome, Li
      Fraumeni syndrome, ataxia telangiectasia, and Cowden's disease. With the
      localization of the BRCA1 gene to chromosome 17q21 and the BRCA2 gene to
      chromosome 13q12, issues surrounding breast cancer susceptibility genetic testing
      are assuming an ever greater measure of importance. The sensitivity and
      specificity for molecular testing of cancer susceptibility genes, however, have
      not been well defined. The progress in presymptomatic genetic testing is further
      hampered by various factors such as the technical difficulty in distinguishing
      mutations from polymorphisms, the number of different mutations identified thus
      far and the possibility of false positive and false negative results. Laboratory
      quality assurance/quality control issues are of paramount importance to avoid
      misleading interpretations. Many issues surrounding genetic screening and
      testing, such as insurance and employment discrimination, privacy, and informed
      consent, are under active debate, and guidelines and standards are under active
      development. It is therefore important to proceed with caution, so that
      irreversible harm resulting from data misinterpretation can be avoided.

PMID- 8879358
TI  - Endometriosis: identification by carbonic anhydrase autoantibodies and clinical
      features.
AB  - Reliably diagnosing endometriosis traditionally requires surgery. To evaluate a
      possible non-surgical method, a case-control series of unexplained infertility
      patients undergoing diagnostic laparoscopy were scored by clinical criteria and
      reactivity to human carbonic anhydrase II by Western blotting. The CA II
      autoantibodies were found in none of the fertile controls, 38 percent of
      infertile controls, 55 percent of stage 1, 50 percent of stage 2, 73 percent of
      stage 3, and 85 percent of stage 4 endometriosis patients. Advanced endometriosis
      was associated with more intense reactivity. Combining clinical and antibody
      scores for infertile groups showed a positive association with disease stage with
      positive predictive values of 76 to 95 percent, negative predictive values of 90
      to 60 percent, and a likelihood ratio of 18.3. It is concluded by us that CA II
      immunoreactivity, clinical, and combined scores all identified stages 2 to 4
      endometriosis patients. However, based on predictive values and likelihood
      ratios, the combined score is best at identifying endometriosis non-surgically.

PMID- 8879359
TI  - Regulation of the onset of meiosis in the developing testis.
AB  - Meiotic division begins the process of spermatogenic maturation leading to sperm
      formation. In contrast to the ovary, in which meiosis is initiated early in
      development, onset of meiosis in the testis is delayed until the time of puberty.
      An assay procedure was utilized to evaluate factors responsible for the
      activation and prevention of meiosis in the developing rabbit testis. Testicular
      specimens from postnatal rabbits at different ages were used to determine if
      meiosis-activating substance (MAS) activity and meiosis-preventing substance
      (MPS) activity could be demonstrated prior to the onset of spermatogenesis. An in
      vitro system in which undifferentiated gonads from 11.5 day old mouse fetuses are
      cultured in test and control media was employed. The findings indicate that MAS
      activity is associated with the onset of spermatogenesis and is also present
      shortly after birth. Activity of MPS is present throughout much of the
      prespermatogenic period, with a decline to reach low levels at the onset of
      spermatogenesis.

PMID- 8879360
TI  - Prognostic potential of cytokines, nitrates, and APACHE II score in sepsis.
AB  - The prognostic potentials of physiological ([Acute Physiologic and Chronic Health
      Evaluation] APACHE II score) and biochemical (Interleukin 6 [IL-6], Interleukin 6
      soluble receptor [IL-6sR], and Interleukin 2 receptor [IL-2R], nitrates) measures
      were evaluated in sepsis. The APACHE II scores were calculated, and
      concentrations of the biochemical markers were measured, based upon information
      and samples obtained from 68 septic patients at time of diagnosis. Outcome
      (survival/non-survival) was determined at the end of the hospital stay associated
      with the septic episode. Statistically significant differences between survivors
      (S) and non-survivors (non-S) were found for APACHE II (p < 0.0001), IL-6 (p <
      0.005), IL-6sR (p < 0.05), IL-2R (p < 0.02). No significant differences were
      found for nitrates. None of the markers could serve individually as an effective
      prognostic indicator. However, those markers demonstrating a significant
      difference between survivors and non-survivors may be able to contribute to a
      multi-parameter prognostic model.

PMID- 8879361
TI  - Diffuse large cell lymphoma of B-cell type associated with reactive
      hemophagocytosis.
AB  - Some lymphomas, virtually all phenotypically of the T-cell type, have been
      associated with the phenomenon of hemophagocytosis. Only two B-cell lymphomas,
      one T-cell-rich and the other an angiocentric lymphoma, have been observed to
      exhibit this phenomenon. A case is reported of a diffuse large cell lymphoma of
      the B-cell type associated with reactive hemophagocytosis. Cytokines or other
      humoral factors produced by the lymphoma are a possible cause, and their effect
      is probably systemic. There is some evidence suggesting correlation of
      hemophagocytosis with tumor aggressiveness.

PMID- 8879362
TI  - Early markers of ventilator-induced lung injury in rats.
AB  - Positive pressure ventilation with hyperdistention of the lungs (PPVHDL) causes
      microscopic lung injury in rats and in mice. This study compared lung lavage and
      serum levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST),
      creatinine phosphokinase (CPK), lung lavage and plasma endothelin-1 (ET-1)
      concentration, lung tissue ET-1 mRNA expression, angiotensin converting enzyme
      (ACE) activity of lung homogenates, and histology of the lung structure in
      control and PPVHDL rats. Rats were anesthetized with pentobarbital. While control
      rats were breathing spontaneously, the PPVHDL rats were ventilated with a rodent
      ventilator delivering 30 percent oxygen, a tidal volume of 18.6 +/- 4.5 ml/kg,
      and a respiratory rate of 55 to 60 per minute. End-tidal CO2 was maintained at 38
      40 mm Hg. After seven hours, rats were killed and the lungs were lavaged. Red
      blood cells were present in the sediment of lavage fluid in PPVHDL rats and their
      lung structure showed severe congestion, alveolar septa filled with red cells,
      and extravasation of red blood cells and inflammatory cells into the alveolar
      space. Lung lavage fluid AST and LDH were significantly higher in the PPVHDL
      compared with the control group (P < 0.03 and P < 0.001, respectively).
      Electrophoresis of the lung lavage LDH showed increased peak-5 in the PPVHDL
      group. Serum LDH, CPK, AST, and potassium concentrations [K]+ were significantly
      higher in the PPVHDL rats whereas their serum total protein level was
      significantly lower than the control group (P < 0.001). Electrophoretic patterns
      of serum and lung lavage protein were similar in both groups indicating a
      transmural passage of serum protein from the intravascular to the intra-alveolar
      space. No significant difference was found in lung tissue ET-1 mRNA expression
      and lung protein concentration between the two groups. Lung ACE activity, in
      contrast, was significantly lower in PPVHDL rats. This study demonstrated that
      moderate alveolar hyperdistention caused significant structural lung damage
      accompanied by decreased ACE activity after seven hours of mechanical ventilation
      and that elevated lung lavage and serum LDH and AST levels in lung lavage and in
      serum might be early markers of ventilator-induced lung injury in this rat model.

PMID- 8879363
TI  - The effect of a synthetic analogue of prostaglandin E2 on wound healing in rats.
AB  - This was a prospective, randomized, double-blind experimental study to assess the
      effect of a long-acting prostaglandin (PG) analogue on wound healing in rats.
      Eight-cm long, dorsal midline skin incisions were made on rats (n = 44) and
      immediately resutured. The treatment group (n = 22) received daily
      intraperitoneal injections of 16,16-dimethyl prostaglandin E2-methyl ester (di
      MPGE2) for 7 days, whereas the controls (n = 22) received normal saline. The rats
      were sacrificed in groups of 11 at 7 and 14 days, respectively. The wounds were
      excised and analyzed. Histology showed that there was increased fibrosis (p <
      0.03) and a decreased number of macrophages (p < 0.02) in the PG group at 7 days.
      Tensile strength and hydroxyproline content also increased but did not attain
      significant levels. The differences between the PG and control groups at 14 days
      similarly did not attain statistical significance. The results suggest that in
      wound healing, the administration of di-MPGE2 may be beneficial during the early
      stages of inflammation, rather than during the later stages of remodelling.

PMID- 8879364
TI  - The effect of storage on Guthrie cards: implications for deoxyribonucleic acid
      amplification.
AB  - The effect of storage on (1) amplifiability of nucleic acid (present at low
      level) and (2) properties of whole blood polymerase chain reaction (PCR)
      inhibitors (present at high levels) in Guthrie card bloodspots was evaluated.
      Natural PCR inhibitors (protein, hemoglobin, iron) were selectively eluted from
      Guthrie cards (1 to 30 mo storage) under nondenaturing conditions and
      quantitated. The PCR was performed by direct amplification. It was found that PCR
      inhibitors become increasingly resistant to elution ("fixed") over time. For
      example, 600 micrograms protein, 1.87 au hemoglobin, and 374 ng iron were
      solubilized from 1 mo bloodspots. In contrast, only 137 micrograms protein (22
      percent), 0.34 au hemoglobin (18 percent), and 147 ng iron (39 percent) were
      solubilized from 30 mo bloodspots. Fixation does not result from excessive
      desiccation since bloodspot weight 2.20 mg +/- 0.21 (1 mo) and 1.92 mg +/- 0.31
      (30 mo) was not significantly changed (p > 0.05). The majority of protein was
      characterized as albumin, and two rbc metal-containing proteins, carbonic
      anhydrase and hemoglobin by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). Despite the presence of "fixed" PCR inhibitors, it
      was found that bloodspots stored 1 to 30 mo could be amplified for two regions
      (98 bp and 491 bp amplicons) encoding the delta F508 cystic fibrosis mutation. It
      is suggested that nucleic acid also becomes "fixed" to the filter paper matrix
      and accounts, in part, for the ability to amplify Guthrie cards by direct PCR and
      low yield of deoxyribonucleic acid (DNA) reported for microextraction methods.

PMID- 8879365
TI  - 5-Fluorouracil in colorectal cancer, a never ending story.

PMID- 8879366
TI  - Radiotherapy and drugs: 'setrons' once again.

PMID- 8879367
TI  - The management of Hodgkin's disease: half a century of change. The Kaplan
      Memorial Lecture.
AB  - The results of treating more than 2600 patients with Hodgkin's disease at
      Stanford over a 35-year period are summarized. It is now a reality that Hodgkin's
      disease can be cured with initial treatment programs in virtually all patients,
      except the elderly. Histologic factors, staging methods, and prognostic groups
      are becoming less and less relevant. The current protocols used at Stanford and
      elsewhere will be reviewed to emphasize that combined modality is really the key
      to improving the cure rate and minimizing late complications.

PMID- 8879368
TI  - Phase I trial design: are new methodologies being put into practice?
AB  - BACKGROUND: The primary goal of phase I studies is to efficiently and accurately
      determine the recommended dose of a new agent for further investigation. Issues
      of concern ranging from the ethics of these trials to selection of starting dose
      and rapidity of dose escalation, have led to suggested modifications of the
      traditional phase I design. We wanted to assess the frequency with which these
      new approaches are being applied to recent phase I trials and, if possible, their
      impact. METHODS: Reports of phase I trials of single agent cytotoxics published
      between 1993 and 1995 were identified by computer search and review of cancer
      journals. Data on starting dose, toxicology, dose escalation method, definition
      of dose limiting toxicity (DLT), actual maximum tolerated dose (MTD) and
      recommended phase II dose were abstracted. RESULTS: Reports of 46 phase I trials
      were identified: 27 were the first clinical studies of 17 new cytotoxic agents
      (group A) and 19 were repeat studies of 14 agents (group B). Starting doses in
      group A were based on preclinical animal toxicology (usually mouse or dog) and
      for group B on previous clinical experience. Dog toxicology appropriately
      influenced starting dose in 3 of 6 trials. The majority of group A (19/27)
      studies employed modified Fibonacci dose escalation; group B studies commonly
      escalated doses by fixed increments. The definition of DLT was highly variable
      across studies. MTD was usually defined as the dose level at which > 2/6 patients
      experienced DLT but several studies required 3-4/6 patients. In 30 trials, the
      recommended phase II dose was one dose level below the MTD; but in 10 trials the
      terms MTD and recommended phase II dose were considered synonymous. CONCLUSION:
      Despite proposed new methodologies (particularly dose escalation) for phase I
      trials, very few are being employed in practice. A concerted effort should be
      made to prospectively evaluate these to determine which provides the best
      combination of safety and efficacy. In addition, the lack of standardization in
      the definition of limiting toxicity is surprising. Those involved in drug
      development should strive for agreement on the acceptable degree of toxicity for
      phase II dose selection.

PMID- 8879369
TI  - Workshop on phase I study design. Ninth NCI/EORTC New Drug Development Symposium,
      Amsterdam, March 12, 1996.
AB  - Many of the methods currently used in phase I trial design date back to the
      1970's. Recently, some investigators have considered whether it might be possible
      to perform more efficient phase I trials that minimize the number of patients
      treated at biologically ineffective doses, maximize the precision of recommended
      phase II doses, and maintain patient safety. The objective of this Workshop was
      to examine aspects of phase I trial design, with consideration of both standard
      and novel approaches. Topics included choice of starting dose level, definition
      of dose-limiting toxicity, development and incorporation of non-toxicity
      endpoints, use of alternate dose escalation schemes, and definitions of tumor
      response and clinical benefit, including consideration of whether these
      determinations from phase I studies should alter the decision to proceed to phase
      II drug evaluation. For each topic, this summary includes a description of the
      standard approach, a summary of the speaker's presentation, and commentary. The
      Workshop initiated discussion and reassessment that are expected to lead to
      testing of some of the suggested alternate approaches.

PMID- 8879370
TI  - 5-Fluorouracil versus 5-fluorouracil plus alpha-interferon as treatment of
      metastatic colorectal carcinoma. A randomized study.
AB  - BACKGROUND: In 1989, S. Wadler reported very promising results (76% response
      rate) with a combination of 5-fluorouracil (5-FU) plus alpha-2a interferon (IFN)
      in the treatment of metastatic colorectal carcinoma (MCRC). In vitro, there are
      several potential explanations for synergism between the two agents. We therefore
      decided in 1989 to start a randomized study comparing 5-FU alone with 5-FU plus
      IFN. PATIENTS AND METHODS: 105 non-pretreated patients with measurable metastatic
      colorectal carcinoma entered into this study. The patients were randomly
      allocated either in arm A (n = 49) with 5-FU: 750 mg/m2 i.v. CI d1-d5 followed by
      750 mg/m2 i.v. bolus once a week, or in arm B (n = 56) with 5-FU as in arm A plus
      IFN 9 x 10(6) IU sub-cutaneously three times a week. RESULTS: After two months of
      treatment we observed 1 CR and 2 PR in arm A (response rate 6.1%), 3 CR and 8 PR
      in arm B (response rate 19.6%), i.e., a significant difference (P = 0.05). Event
      free survival was significantly higher in arm B (6 months) than in arm A (2
      months) (P < 0.01), while median survival was slightly higher in arm B (12
      months) than in arm A (10 months) (P < 0.05). For overall survival the difference
      was not significant after adjustment on center treatment and baseline Karnofsky
      status (P = 0.13). Toxicity was also greater in arm B. Sixteen percent of
      patients in arm A and 36% in arm B experienced certain grade 3-4 side effects (P
      < 0.05). CONCLUSION: 5-FU plus IFN is more effective than 5-FU alone in terms of
      response rate, event free survival but not of overall survival. 5-FU plus IFN is
      more toxic. As IFN has no demonstrated efficacy in MCRC as a single agent, this
      study suggests that IFN is acting as a 5-FU modulatory agent. The response rate
      observed (19.6%) is similar to the results obtained elsewhere with 5-FU plus
      leucovorin.

PMID- 8879371
TI  - Outpatient weekly high-dose continuous-infusion 5-fluorouracil plus oral
      leucovorin in advanced colorectal cancer. A phase II trial. Spanish Cooperative
      Group for Gastrointestinal Tumor Therapy (TTD).
AB  - BACKGROUND: In a previous phase I-II trial we showed that the maximum tolerable
      dose (MTD) of 5-fluorouracil (5-FU) in a weekly 48-hour continuous infusion (CI)
      was 3.5 g/m2. In a subsequent confirmative phase II trial with 85 evaluable
      patients, a 38.5% response rate was obtained, and a median survival of 12 months.
      These data were comparable to those achieved by biochemical modulation of 5-FU
      with leucovorin. On this basis we attempted to modulate high-dose 5-FU (3 g/m2)
      with oral leucovorin (LV) but the regimen was too toxic and the dose had to be
      reduced. A new phase II trial with 2 g/m2/week plus oral leucovorin was planned.
      PATIENTS AND METHODS: From July 1992 to June 1994, 110 previously untreated
      patients with advanced, measurable colorectal cancer were included in a
      multicenter study. The patients received, on an outpatient basis, 5-FU 2 g/m2 by
      continuous infusion for 48 hours once a week until progression or the appearance
      of toxic effects. Oral leucovorin (60 mg every six hours) was also given during
      the 5-FU infusion. RESULTS: Patients received a median dose intensity of 5-FU of
      1.6 g/m2/week (range 0.9-2). Three complete responses and 36 partial responses
      were observed. The overall response rate was 37.5% (95% CI, 28% to 46.8%), the
      median time to progression 7.4 months and median survival 14.5 months. W.H.O.
      grade 3 diarrhea occurred in 27 patients (24.5%); grade 3 mucositis was observed
      in 9 (8.1%) patients and grade 4 in one. Grade 3 nausea and vomiting was reported
      in 13 (11.7%) patients, while grade 3 hand-foot syndrome was detected in only 5
      (4.5%). Grade 4 leukopenia occurred in one patient and grade 3-4 thrombocytopenia
      in two. CONCLUSIONS: Oral leucovorin modulation of weekly 48-hour continuous
      infusion of 5-FU at 2 g/m2 is an active regimen, with diarrhea and mucositis as
      the main limiting toxic effects. Its antitumor activity does not seem superior to
      that obtained with a weekly 48-hour continuous infusion of 5-FU alone at a dose
      of 3.5 g/m2.

PMID- 8879372
TI  - A randomised placebo controlled study with ondansetron in patients undergoing
      fractionated radiotherapy.
AB  - BACKGROUND: There are few randomised studies comparing anti-emetic drugs for the
      prevention of nausea and vomiting in patients treated with fractionated
      radiotherapy. The aim of the study was to compare the anti-emetic efficacy of 8
      mg dose ondansetron twice a day with placebo. MATERIALS AND METHODS: One hundred
      eleven patients who were to commence a course of 10 or more daily fractionated
      radiotherapy including the abdomen were included in the study. The patients
      recorded daily emesis, nausea and bowel habit and graded weekly symptoms of
      nausea, vomiting, diarrhoea and lack of appetite. The EORTC C30 questionnaire was
      completed. RESULTS: 67% of patients given ondansetron had complete control of
      emesis compared with 45% of patients with placebo (P < 0.05). The number of
      emetic episodes recorded on the worst day was 1.4 for the ondansetron group and
      3.1 for the placebo group (P < 0.01). Patients given ondansetron had fewer days
      with emesis and nausea compared with placebo (P < 0.05). The mean sum score of
      patients weekly grading of symptoms showed that the ondansetron group had less
      inconvenience than the placebo group (P < 0.05). This difference persisted during
      the first three weeks, but not thereafter. Similarly, some quality of life
      measures showed significant differences in favour of the ondansetron group. More
      patients (n = 13) withdrew due to lack of efficacy in the placebo group compared
      with patients (n = 8) in the ondansetron group. CONCLUSIONS: The present study
      illustrates that prophylactic anti-emetic administration of ondansetron is
      effective in preventing nausea and vomiting in patients undergoing fractionated
      radiotherapy of the abdomen.

PMID- 8879373
TI  - Chemotherapy improves survival and quality of life in advanced pancreatic and
      biliary cancer.
AB  - BACKGROUND: In certain patients with pancreatic and biliary cancer, chemotherapy
      may relieve tumour-related symptoms, improve quality of life and possibly prolong
      survival. The extent of these improvements is not completely known in spite of
      the extensive use of this treatment modality. The aim of this study was to
      estimate any gain in the quantity and quality of life produced by chemotherapy in
      patients with pancreatic and biliary cancer. PATIENTS AND METHODS: Between
      January 1991 and February 1995, 90 eligible patients with pancreatic or biliary
      cancer were randomized to either chemotherapy in addition to best supportive care
      or to best supportive care. Chemotherapy was allowed in the latter group if the
      supportive measures did not lead to palliation. Chemotherapy was either
      sequential 5-fluorouracil/leucovorin combined with etoposide (FELv) or, in
      elderly and poor performance patients, the same regimen without etoposide (FLv).
      Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS: Mean
      scale scores in the QLQ-C30 improved more often/deteriorated less frequently in
      the chemotherapy group than in the best supportive care group. More patients in
      the chemotherapy group (36%, 17/49) had an improved or prolonged high quality of
      life for a minimum period of 4 months compared to those in the best supportive
      care group (10%, 4/41, P < 0.01). Overall survival was significantly longer in
      the chemotherapy group (median 6 vs. 2.5 months, P < 0.01). Also, the quality
      adjusted survival time was longer for patients randomized to chemotherapy (median
      4 vs. 1 months, P < 0.01). The effects were seen both in pancreatic and biliary
      cancer. CONCLUSIONS: The results show that chemotherapy can add to both quantity
      and quality of life in advanced pancreatic and biliary cancer. The number of
      patients who benefit from treatment is, however, still limited; for this reason
      careful selection before, and close monitoring during, treatment are necessary.

PMID- 8879374
TI  - Treatment of metastatic renal cell carcinoma with constant-rate floxuridine
      infusion plus recombinant alpha 2b-interferon.
AB  - BACKGROUND: Floxuridine (FUDR) and alpha-interferon (IFN) are active agents in
      advanced renal cell carcinoma, with different dose-limiting toxic effects and
      antitumor synergism in experimental models. The main purpose of this phase II
      study was to assess the activity and toxic effects of a combination of FUDR and
      alpha 2b-IFN in metastatic renal cell carcinoma. PATIENTS AND METHODS: Metastatic
      renal cell carcinoma patients with measurable disease entered the study. FUDR was
      administered as a constant-rate continuous infusion for 14 days every 28 days at
      a starting daily dose of 0.1 mg/kg and with dose escalations of 0.025 mg/kg/day
      at each subsequent cycle if WHO > or = 2 toxicity had not occurred. IFN-alpha 2b
      10 x 10(6) I.U. was administered intramuscularly 3 times per week. RESULTS: Forty
      two patients entered the study and a total of 272 cycles of FUDR + alpha 2b-IFN
      were administered. In 41 evaluable patients WHO grade III-IV toxic effects
      included nausea and vomiting (22%), diarrhea (32%), stomatitis (12%), fatigue
      (27%) and anorexia (12%). It was possible to increase the initial FUDR does in 21
      (50%) patients; the median FUDR dose intensity was 0.35 mg/kg/week (range 0.18
      0.54). Among 39 evaluable patients, 3 (7.5%) complete and 10 (25.5%) partial
      responses were observed (response rate 33%, 95% confidence interval (CI) 19%-50%)
      which lasted a median of 13 months (5.5-40+). Responses also occurred in liver
      (2), in patients pretreated with systemic therapy (5) and in patients who had
      other unfavourable prognostic characteristics (7). Median progression-free and
      survival times were 9 and 16 months, respectively. CONCLUSIONS: In this study
      FUDR + alpha 2b-IFN demonstrated interesting activity in metastatic renal cell
      carcinoma, showing promise also in patients with unfavourable prognostic
      characteristics. The antitumor activity of FUDR and alpha 2b-IFN seems to be
      cumulative, but cumulative toxicity is also observed. These results require
      confirmation in randomised trials.

PMID- 8879375
TI  - Comparison of the diagnostic and prognostic value of biological markers in
      neuroblastoma. Proposal for a common methodology of analysis. SENSE group.
AB  - BACKGROUND: The prognosis of pediatric neuroblastoma depends both on clinical
      presentation and on certain cellular and molecular characteristics. Screening
      programs have been initiated in infants of less than one year of age, based on
      the hypothesis that neuroblastoma progresses from early to late clinical stages
      through a classical multistep process linked to an accumulation of molecular
      abnormalities. However, recent analyses suggest that most cases discovered by
      screening are low stage tumors considered as dysembryogenetic residues devoid
      from major abnormalities and that high-grade tumors with molecular abnormalities
      are unrelated diseases. AIM OF THE REVIEW: To confirm one or the other
      hypothesis, and eventually identify biological factors possibly responsible for
      the initiation and progression of the disease, it is of utmost importance that
      all investigators agree on biological criteria for analysis when neuroblastoma
      tissue is available in screened and unscreened populations. This paper reviews
      the biological tools available for prognosis in neuroblastoma, the priority for
      analysis of biological markers according to both methodological reliability and
      feasibility, and the conditions of tissue storage for further analysis of these
      biological markers. CONCLUSION: The standardized biological evaluation of
      neuroblastoma will allow to collect sufficient data for multivariate analysis;
      such analysis is now fundamental if one wants to clearly define the respective
      impacts of biological abnormalities on neuroblastoma progression.

PMID- 8879376
TI  - Patient-controlled analgesia with oral methadone in cancer pain: preliminary
      report.
AB  - BACKGROUND: Methadone is a very useful drug in cancer pain because of its low
      cost, lack of active metabolites, high oral availability, and the rapid onset of
      its analgesic effect. It seems to be well tolerated in patients with difficult
      pain syndromes who are receiving high doses of opioids, and it may deter the
      development of tolerance, but a high individual variation in terminal elimination
      half-life can result in different rates and extents of drug accumulation. For
      this reason, oral patient-controlled analgesia with methadone was used in 24
      advanced-disease patients with pain. PATIENTS AND METHODS: A regimen of self
      administered oral methadone at fixed doses and flexible patient-controlled dosage
      intervals to achieve adequate analgesia, while avoiding toxic effects of
      methadone accumulation, was used in 24 patients requiring opioid therapy. After a
      priming period of three days with fixed doses of 3-5 mg three times a day for
      naive patients and 50% of the morphine equivalent of methadone in patients
      switched from morphine, patients and relatives were instructed to maintain the
      night-time dose and to administer a second dose when the pain recurred. When more
      than four doses of methadone a day were used, an increase of the dosage was
      prescribed. Continuous pain assessment and monitoring of symptoms were offered.
      RESULTS: The majority of patients achieved good pain relief until death, and
      three were switched to very low doses of subcutaneous morphine in their final
      days. The methadone escalation index was about 2% a day, with a mean dosage
      increase of 0.3 mg a day for an average of 60 days of treatment at doses ranging
      from 9 to 80 mg. The plasma concentration in 14 patients ranged from 0.013 to
      0.273 mcg/ml with dosages of 20-80 mg during chronic treatment. A mean of 2.4
      doses a day was reported, including the fixed night-time dose. The extent of side
      effects was considered acceptable. CONCLUSION: Patient-administered analgesia
      with oral methadone appears to be a simple, cheap and relatively safe technique
      for controlling cancer pain, permitting individualization by the patient him- or
      herself and avoiding the risk of accumulation. Continuous assessment is
      necessary.

PMID- 8879377
TI  - Sensitive detection of circulating breast cancer cells by reverse-transcriptase
      polymerase chain reaction of maspin gene.
AB  - BACKGROUND: Maspin, a recently identified protein related to the family of
      serpins, is believed to play a role in human breast cancer. In an effort to
      improve the present methods of detection, we have developed a reverse
      transcriptase polymerase chain reaction (RT-PCR) assay for maspin transcript to
      identify small numbers of mammary carcinoma cells in the peripheral blood and
      bone marrow of patients with breast cancer. PATIENTS AND METHODS: Five non
      neoplastic mammary tissue samples, 13 breast cancer specimens as well as 17
      peripheral blood and 4 bone marrow samples from normal subjects were screened for
      the presence of maspin mRNA by RT-PCR. The same assay was applied to peripheral
      blood or bone marrow samples obtained from 29 patients with stages I to IV breast
      cancer. RESULTS: By RT-PCR it was possible to amplify maspin mRNA in all of the
      primary and metastatic breast cancer specimens, but in none of the normal
      hemopoietic samples from healthy donors. Thus, detection of maspin transcript in
      the peripheral blood or marrow of a patient known to have breast cancer is
      indicative of the presence of mammary carcinoma cells. In reconstitution
      experiments, maspin RT-PCR reliably detected 10 mammary carcinoma cells in 1
      million normal peripheral-blood mononuclear cells (PBMCs). None of the 9 patients
      with stages I, II, or III breast cancer had maspin transcript in peripheral
      blood. Of note, 3 of 9 patients with stage IV breast cancer receiving systemic
      therapy at the time of sample collection, but only 1 of 11 patients with stage IV
      not receiving therapy, had detectable maspin transcript in peripheral blood.
      Moreover, 3 marrow specimens from stage IV patients tested positive by this
      assay. CONCLUSIONS: This pilot study suggests that maspin RT-PCR assay is a
      sensitive, specific and sufficiently rapid method for detection of small numbers
      of circulating cells and marrow micrometastases in breast cancer patients. The
      possibility of applying this assay in the detection of tumor cell contamination
      of both marrow and stem-cell apheresis harvests of breast cancer patients merits
      further investigation.

PMID- 8879378
TI  - Expression of the human major vault protein LRP in human lung cancer samples and
      normal lung tissues.
AB  - BACKGROUND: The recently discovered LRP protein has been shown to be involved in
      drug resistance and possibly in detoxification processes. MATERIALS AND METHODS:
      To study the relation between LRP expression and exposure to cigarette smoke, LRP
      immunoreactivity was evaluated in 39 paraffin embedded normal lung tissues
      derived from patients operated on for pneumothorax, and related to amount of pack
      years smoked. We also studied the LRP protein expression in 36 non-small-cell
      lung cancer (NSCLC) samples and related the expression to patient characteristics
      and survival. Furthermore 17 lung tumor samples (10 NSCLC and 7 SCLC) derived
      from patients treated with chemotherapy were analysed in order to investigate the
      relation between LRP or MRP expression and the patient's response to
      chemotherapy. RESULTS: In the normal lung tissues, LRP intensity levels were not
      correlated to the amount of pack years smoked, although a trend was seen for
      higher LRP intensity levels in patients who smoked more than 10 pack years. LRP
      expression was significantly higher in NSCLC samples than in SCLC samples, and
      all SCLC samples displayed very low LRP expression. Within NSCLC, squamous cell
      and adenocarcinomas had higher LRP expression than large cell undifferentiated
      and mixed tumors. In NSCLC patients LRP expression was not a prognostic factor
      for survival. At initial analysis LRP expression levels did not predict for the
      response to chemotherapy. Only 3 out of 17 patients expressed MRP, and all SCLC
      samples were MRP negative. CONCLUSIONS: Striking different expression levels were
      seen between NSCLC and SCLC for both LRP and MRP. In a preliminary analysis LRP
      expression was not predictive for response to chemotherapy in lung cancer
      patients. In pneumothorax patients LRP levels were not correlated with the amount
      of pack years smoked.

PMID- 8879379
TI  - Tumour lysis syndrome, case report and review of the literature.

PMID- 8879380
TI  - Oral ifosfamide/mesna versus intravenous ifosfamide/mesna in non-small-cell lung
      cancer: a randomized phase II trial of the EORTC lung cancer cooperative group.
AB  - BACKGROUND: Chronic oral administration of anticancer drugs may offer therapeutic
      advantages. PATIENTS AND METHODS: A total of 68 patients with advanced non-small
      cell lung cancer, not previously treated by chemotherapy, were randomized to
      receive either ifosfamide given orally (OSI) at a dose of 1 g/day for 14 days
      every 4 weeks, or as a 1-hour intravenous infusion (IVI) at a dose of 1.6
      g/m2/day for 5 days every 4 weeks. According to the route of ifosfamide
      administration, patients received either mesna i.v. or mesna film-coated tablets
      for uroprotection. RESULTS: Eight patients were found to be ineligible for the
      study and therefore excluded for all analyses. Thirty-three patients received
      IVI, and 27 patients OSI. One patient randomized to OSI died before treatment was
      initiated, leaving 59 patients fully evaluable for toxicity. Hematological
      toxicity was less severe for patients on OSI, but CNS toxicity was reported more
      frequently on OSI (39%; 12% grade III/IV), than on IVI (15%; 9% grade III/IV),
      which caused the premature close of the study. Other non-hematological adverse
      events were of modest clinical significance and comparable in both arms. Forty
      nine patients were considered evaluable for response: in the IVI arm, 5 (17%) of
      the 29 evaluable patients obtained a partial remission, and 7 patients a no
      change (24%). In the OSI arm, 2 (10%) of the 20 evaluable patients obtained a
      partial remission, and 11 (52%) a stable disease. CONCLUSIONS: Both arms have
      some activity in non-small-cell lung cancer; while OSI was less myelosuppressive
      than IVI, it was associated with a higher incidence of CNS toxicity. Oral
      administration of ifosfamide, in the schedule and daily dose tested here cannot
      be recommended.

PMID- 8879381
TI  - Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma.
      A phase II trial of 22 patients.
AB  - BACKGROUND: To evaluate the activity of CAP regimen in advanced salivary gland
      carcinomas. PATIENTS AND METHODS: Twenty-two patients with advanced salivary
      gland carcinomas were treated according to the CAP regimen. All patients were
      previously treated with surgery and/or radiotherapy and/or chemotherapy. Seven
      patients had local or locoregional disease, nine patients had local and
      metastatic disease, six patients had metastatic disease only. The most common
      histologies were included. RESULTS: Of 22 patients, six achieved a partial
      response (27%, 95% CI: 11%-50%): no complete response was observed. Response
      duration ranged between 3 and 13 months (median seven months). The median
      survival time for the entire series was 21 months. CONCLUSIONS: In this
      investigation, on 22 consecutive patients, CAP combination provided an overall
      response rate of 27%. This study confirms that, at present, available drugs yield
      poor results, either as single agents or as combination therapy.

PMID- 8879382
TI  - Low-dose prednisone and increased risk of development of bone metastases.

PMID- 8879383
TI  - Ifosfamide encephalopathy and methylene-blue: a case report.

PMID- 8879385
TI  - Palliative care versus euthanasia?

PMID- 8879384
TI  - Chemotherapy of biliary tract cancer with mitomycin-C and 5-fluorouracil
      biologically modulated by folinic acid. A phase II study.

PMID- 8879386
TI  - Cardiac assessment prior to vascular surgery: is dipyridamole-sestamibi
      necessary?
AB  - Dipyridamole-sestamibi (PMIBI) is recommended prior to vascular surgery in
      patients with > or = 1 Eagle criteria (Q waves, history of ventricular ectopy,
      diabetes, advanced age, and/or angina). To review our cardiac morbidity and
      mortality and the need for preoperative PMIBI, we reviewed 109 consecutive
      patients with a mean age of 59 years who underwent 145 elective major vascular
      procedures over a 1-year period. Seventy patients (with a mean of 0.8 Eagle
      criteria) underwent 92 vascular procedures without preoperative PMIBI and without
      coronary revascularization. Thirty-one patients (with a mean of 1.1 Eagle
      criteria) underwent 39 procedures without coronary revascularization following
      PMIBI, which showed reversible ischemia in seven and a fixed defect in 10;
      findings were normal in 14. Preoperative coronary bypass or angioplasty was
      limited to eight patients (14 procedures, mean of 1.6 Eagle criteria) who had
      unstable angina with (2 patients) or without (6 patients) acute myocardial
      infarction. There were four perioperative myocardial infarctions (2.8%), seven
      cardiac events overall (4.8%), and one cardiac death (0.7%). Three (43%) of the
      seven cardiac events occurred in patients with a normal scan or fixed defect on
      PMIBI imaging. In the absence of unstable angina, PMIBI had a sensitivity of only
      25% and a specificity of 80% for cardiac events. We conclude that among patients
      without severe cardiac symptoms (1) PMIBI has a very limited ability to identify
      patients at risk for cardiac complications, and (2) preoperative PMIBI is neither
      necessary nor cost-effective.

PMID- 8879387
TI  - Cardiac evaluation of the diabetic patient prior to peripheral vascular surgery.
AB  - The benefit of preoperative cardiac evaluation in the diabetic patient undergoing
      peripheral vascular surgery is uncertain. To investigate this issue we performed
      a retrospective review of 192 procedures performed in diabetic patients for
      chronic lower extremity arterial occlusive disease. The incidence of adverse
      postoperative cardiac events was determined, as well as its association with
      several preoperative factors including symptoms of coronary artery disease (CAD),
      extent and results of preoperative noninvasive cardiac evaluation, and operative
      site (aorta vs. lower extremity). The overall death and cardiac complication
      rates were 10.2% for lower extremity and 25.7% for aortic procedures (p = 0.02).
      For myocardial infarction and cardiac death alone, the rates were 5.1% and 5.7%,
      respectively (p > 0.10). Although a history of symptomatic CAD predicted the
      occurrence of any cardiac complication (28.3% vs. 8.2% [p < 0.01] for the aortic
      and lower extremity revascularization groups combined), no factor was found to be
      associated with the occurrence of myocardial infarction and cardiac death alone.
      In patients with a history of symptomatic CAD, there was no significant
      difference in the incidence of complications whether or not preoperative
      noninvasive cardiac testing was performed (28.1% vs. 28.6%, p > 0.10) or, if
      testing was performed, if the results were abnormal or normal (35.3% vs. 20.0%, p
      > 0.10). Similar results were obtained in patients with no history of symptomatic
      CAD. In summary, this retrospective review of our experience with noninvasive
      evaluation to detect CAD in diabetic patients undergoing peripheral vascular
      surgery failed to show any benefit in terms of reducing the incidence of
      postoperative cardiac events.

PMID- 8879388
TI  - Comparison of the deployment and healing of thin-walled expanded PTFE stented
      grafts and covered stents.
AB  - This study evaluated the deployment and short-term healing of thin-walled
      expanded polytetrafluoroethylene (ePTFE) stented grafts and covered stents as
      endoluminal prostheses in normal canine aortas and in an abdominal aortic
      aneurysm (AAA) model. Stented grafts consisted of a 7 cm length of 3 mm internal
      diameter ePTFE graft (Impra, Inc., Tempe, Ariz.) with two P-188 Palmaz stents
      (Johnson & Johnson Interventional Systems, Warren, N.J.) deployed along the inner
      surface of the ends of the graft to secure the prosthesis to the arterial wall.
      Covered stents were fabricated by placing a 3.7 cm length of 3 mm internal
      diameter thin-walled ePTFE graft over a P-394 Palmaz stent. Four covered stents
      and four stented graft prostheses (two of each prototype in the normal canine
      aorta and AAA model) were implanted in eight animals. One prosthesis of each type
      in each model was removed at 30 days and one at 60 days. Prior to removal,
      prostheses were evaluated by CT scan, arteriography, and intravascular ultrasound
      imaging with values compared to those obtained when the prostheses were deployed.
      Gross inspection and microscopic evaluation were performed at scheduled
      explantation. In general, the stented grafts were more difficult to accurately
      deploy. Healing and maintenance of long-term patency without significant luminal
      obstruction or occlusion occurred in only one 30-day sample in a normal canine
      aorta. The 30-day stented graft specimen that had been implanted in an AAA and
      required the addition of a covered stent to seal a maldeployment of the distal
      segment was also patent. The 60-day stented graft in the normal canine aorta was
      occluded with narrowing of the graft between the stents. The 60-day stented graft
      in the AAA was patent with one central fold and thrombus occupying approximately
      20% to 30% of the lumen at this site. In contrast, the covered stent devices were
      less difficult to accurately deploy. All of the covered stent devices were patent
      with well-incorporated surfaces. Deployment of covered stents was more accurate
      and less complicated compared to stented grafts. All patent endoluminal
      prostheses and stent surfaces were well incorporated into aortic tissues.
      Problems with graft narrowing, folding, and subsequent thrombosis occurred in the
      unstented segments of the stented grafts. These preliminary findings support the
      further development and use of completely supported (stented) devices as
      endoluminal prostheses.

PMID- 8879389
TI  - Intraoperative color duplex scanning for infrainguinal vein grafts.
AB  - We compared the findings of intraoperative color duplex scanning and completion
      arteriography in patients undergoing infrainguinal vein bypasses to identify
      hemodynamic abnormalities that could result in a predisposition to early or late
      graft failure. We reviewed the records of 72 patients who underwent 81 vein
      bypass graft procedures. Three intraoperative diagnostic methods were used. In 28
      procedures (group I) both color duplex and completion arteriography were used, in
      21 procedures (group II) only color duplex was used, and in 26 procedures (group
      III) only completion arteriography was used. Grafts were followed using a duplex
      surveillance protocol for a mean interval of 16.1 months. Nine grafts in group I
      showed an abnormality on the duplex scan but not on the completion arteriogram.
      Seven grafts had a peak systolic velocity (PSV) greater than 200 cm/sec and two
      had a PSV less than 45 cm/sec. These findings led to six immediate repairs, one
      early revision, and two late revisions. Arteriography demonstrated additional
      defects in two procedures but repairs were not performed. In group II duplex
      scans showed an abnormality in eight procedures (seven grafts with PSV 200 to 250
      cm/sec and one graft with a retained valve) resulting in three immediate repairs
      and five late revisions. In the remaining 13 procedures in group II, duplex scans
      were normal and no revisions were required during follow-up. In group III defects
      were detected by arteriography in four procedures (> 50% stenosis in three grafts
      and one arterial spasm) leading to three immediate repairs. In the remaining 22
      studies arteriograms were interpreted as normal; however, seven of these grafts
      required late revisions. Our data suggest that grafts that appear normal on
      intraoperative duplex scans are not likely to develop a stenosis requiring
      revision. Intraoperative duplex ultrasound may be superior to completion
      arteriography.

PMID- 8879390
TI  - Factors influencing the outcome of paramalleolar bypass grafts.
AB  - Reported patency rates for paramalleolar bypass grafts have varied widely. To
      determine factors predictive of outcome, we reviewed our experience with 80
      consecutive paramalleolar reconstructions in 68 patients performed between
      December 1986 and May 1995. All procedures were performed for critical limb
      ischemia defined as nonhealing ulcer or gangrene (n = 72, 90%) and rest pain (n =
      8, 10%). Risk factors present were diabetes (n = 52, 65%), hypertension (n = 64,
      80%), and history of smoking (n = 57, 71%). Of the 80 bypasses, in situ saphenous
      vein conduits were used in 39 (49%). In the remainder non-in situ grafts were
      used including reversed vein (n = 25, 31%), composite vein (n = 11, 14%),
      polytetrafluoroethylene (PTFE; n = 4, 5%), and composite PTFE/vein (n = 1, 1%).
      The recipient vessel was the dorsalis pedis artery in 26 procedures (33%), the
      posterior tibial artery in 32 (40%), the distal anterior tibial artery in 18
      (22%), and tarsal or plantar vessels in four (5%). Primary and secondary patency
      rates were 52% and 68% at 36 months, respectively, by life-table analysis. The
      limb salvage rate was 86% and patient survival was 56% at 36 months. Secondary
      patency was significantly higher in diabetic patients than in their nondiabetic
      counterparts (86% vs. 50% at 36 months, p < 0.03). Similarly, patients undergoing
      in situ reconstructions had better secondary patency than patients with non-in
      situ conduits (86% vs. 51% at 36 months, p = 0.03). Diabetic patients tended to
      be younger (median age 69 years vs. 72 years) and had fewer prior reconstructions
      (7 [13%] vs. 13 [46%], p < 0.01). Diabetic patients received a higher proportion
      of in situ reconstructions (54% vs. 39%) but the difference did not achieve
      statistical significance (p = 0.09). We conclude that the long-term patency for
      paramalleolar bypass is acceptable but inferior to reported figures for more
      proximal reconstructions. The factors that most influence patency are the quality
      of the venous conduit and the presence of diabetes. The improved patency seen in
      diabetic patients is likely related to the fact that these patients require
      paramalleolar bypass at an earlier age, are less likely to have had previous
      reconstructions, and are therefore more likely to have a good quality venous
      conduit.

PMID- 8879391
TI  - Combined renal artery stenosis and aortic aneurysm: treatment options.
AB  - The purpose of this study was to analyze outcomes of two different treatment
      strategies in patients treated for renal artery (RA) stenosis and a coincidental
      abdominal aortic aneurysm (AAA). A total of 50 patients were encountered who
      required treatment for concomitant RA stenosis and an AAA from 1980 to 1994.
      Simultaneous operative aortic and RA reconstruction was done in 32 patients,
      whereas 18 patients where treated with preoperative percutaneous transluminal
      renal artery angioplasty (PTRA). The two groups were well matched with respect to
      age, AAA size, incidence of hypertension, preoperative creatinine level, and
      creatinine clearance (all p values > 0.07). Aortorenal bypass (18 RAs),
      reimplantation (18 RAs), or endarterectomy (2 RAs) was performed to correct a
      mean RA stenosis of 88%, whereas 23 RAs (91% mean stenosis) were treated with
      preoperative PTRA. PTRA failed in four patients with RA stenosis, and they were
      successfully treated with surgery (3 bypasses and 1 reimplantation). Statistical
      analysis did not demonstrate a significant difference between these four failed
      PTRA patients, the 14 successful PTRA patients, and the 32 RA reconstruction
      patients in terms of operating time (p = 0.15), operative blood loss (p = 0.20),
      intensive care unit days (p = 0.71), or total hospital days (p = 0.94). Among the
      40 patients available for follow-up, hypertension was cured in seven, improved in
      10, unchanged in 15, and worse in eight with no difference demonstrated between
      the groups (p = 0.73). These data suggest that preoperative PTRA has no specific
      advantage over surgical RA reconstruction in patients with concomitant RA
      stenosis and AAA. Failed PTRA did not preclude or complicate subsequent operative
      RA revascularization.

PMID- 8879392
TI  - Spontaneous necrosis of the skin associated with cryofibrinogenemia,
      cryoglobulinemia, and homocystinuria.
AB  - Cryofibrinogenemia has been associated with a variety of skin manifestations
      including purpura, livedo reticularis, and ulceration. Our patient, who had
      undergone axillobifemoral bypass 5 years previously, presented following the
      spontaneous development of a necrotic wound involving the left groin scar. The
      location of the wound suggested the possibility of underlying graft infection,
      but indium-111 white blood cell scan and MRI failed to show any evidence of
      infection. The patient was initially treated with oral antibiotics and outpatient
      debridement with no improvement. A more aggressive approach with inpatient
      operative debridement and intravenous antibiotics produced moderate improvement.
      Three months later, the patient developed an identical necrotic wound in the
      right groin and subsequently a third lesion involving a scar distant from any of
      the patient's grafts. No evidence of active vasculitis was seen on microscopic
      examination of the excised tissues. Cryoglobulin and cryofibrinogen assays were
      positive, and urinary and plasma homocysteine levels were elevated. The patient
      was subsequently treated with stanozolol, a low-methionine diet, and outpatient
      intravenous antibiotics with rapid improvement of her wounds. In patients with
      spontaneous ulceration of the extremities, particularly when they do not respond
      appropriately to standard therapy, the possibility of cryoglobulinemia or
      cryofibrinogenemia should be considered.

PMID- 8879393
TI  - Ruptured renal artery aneurysm during pregnancy.
AB  - A 38-year-old woman (gravida 4, para 1) underwent arteriography at 19 weeks'
      gestation after two exploratory laparotomies had failed to identify a source of
      retroperitoneal and intra-abdominal hemorrhage. The arteriogram demonstrated a
      large right renal artery aneurysm (RAA) and a very small left RAA. Emergency
      repair of the aneurysm was attempted but was impossible, so a right nephrectomy
      was performed. The fetus had died prior to arteriography and a cesarean section
      was performed concomitantly. The postoperative course was unremarkable. RAAs are
      rare and usually asymptomatic, but pregnancy is associated with a higher risk of
      rupture. Prior to 1970, reported rupture occurred most often on the left side,
      during the third trimester, and was associated with a 92% maternal mortality and
      a 100% fetal mortality rate. Since 1970, published reports have not shown a left
      sided predominance, and survival after this catastrophic event has greatly
      improved, even though preoperative diagnosis is still rare. The possibility of a
      ruptured RAA should be considered in pregnant women with evidence of
      retroperitoneal hemorrhage. Arterial repair should be attempted but has not been
      feasible in most cases. This case was unusual because it occurred during the
      second trimester of pregnancy. Recent cases and technical considerations
      regarding repair are discussed.

PMID- 8879394
TI  - A new technique for hemodialysis access surgery: use of the pneumatic tourniquet.
AB  - The purpose of this study was to determine whether tourniquet occlusion could be
      safely used on the upper extremity for vascular control during hemodialysis
      access surgery. The hospital and outpatient records of 44 patients undergoing 105
      hemodialysis access procedures were retrospectively reviewed. In 48 procedures
      tourniquet occlusion was used for vascular control, whereas in 57 procedures
      vascular clamps were used. In those procedures in which the tourniquet was used,
      the mean tourniquet time was 30 minutes and the mean tourniquet pressure was 242
      mm Hg. The operative time was significantly less in the tourniquet group as
      compared to the clamp group (72.5 minutes vs. 84 minutes, respectively; p =
      0.029). There was no statistically significant difference in the incidence of
      nerve injury, bleeding, hematoma, vascular steal, infection, or swelling between
      the two groups. There were no complications related specifically to the use of
      the tourniquet. There was no difference in primary patency in comparing the
      tourniquet control group with the clamp control group (p > 0.5). The use of a
      pneumatic tourniquet for vascular control during hemodialysis access surgery
      allows for a faster, technically easier operation with no increase in the
      complication rate and no effect on primary patency.

PMID- 8879395
TI  - Continuous pulse amplitude monitoring of infrainguinal bypass grafts in the first
      24 postoperative hours.
AB  - To evaluate continuous pulse amplitude monitoring (CPAM) as a method for early
      postoperative graft surveillance following infrainguinal bypass surgery, a
      prospective observational study was carried out in 34 consecutive infrainguinal
      bypass grafts. CPAM tracings were compared with pre- and postoperative pulse
      palpation, ankle/brachial index (ABI) measurements, and pulse volume recordings
      (PVR). The utility of each method was defined by its ability to demonstrate graft
      patency in the first 24 hours. Pulse palpation was considered a useful monitoring
      tool if a postoperative pedal pulse was found in the absence of palpable
      preoperative pulses. The ABI qualified in this respect if a postoperative
      increase of at least 0.25 could be demonstrated; for PVR tracings an increase of
      at least one category was required. The utility of CPAM was established by an
      increase of at least 5 mm compared to the preoperative values. There were no
      early graft failures. We were therefore unable to calculate the ability of the
      studies to predict graft failure. The percentages (95% confidence limits) for
      which pulse palpation, ABI, and PVR were found capable of demonstrating graft
      patency were 50% (range 34% to 66%), 53% (range 36% to 70%), and 71% (range 54%
      to 83%), respectively. CPAM appeared to be far superior to these three methods
      with a utility of 94% (range 81% to 98%; p < 0.05). Patient and operator
      acceptability of CPAM was high. Skin pressure problems are a potential risk if
      the CPAM probe is left attached to the skin for more than 24 hours. CPAM was a
      valuable and reliable means of monitoring infrainguinal vascular reconstructions.
      Apart from being inexpensive, continuous, objective, and simple, CPAM is
      noninvasive and painless. It is advisable to remove the probe 24 hours after
      surgery, when the most crucial period for graft monitoring has passed.

PMID- 8879396
TI  - Corotid endarterectomy for symptomatic carotid artery disease demonstrated by
      duplex ultrasound with minimal arteriographic findings.
AB  - Ulcerated or irregular heterogeneous carotid plaque as seen by duplex ultrasound
      can cause hemispheric transient ischemic attacks (TIAs) and/or a cerebrovascular
      accident, even if only associated with nonsignificant carotid stenosis on
      arteriography. The purpose of this study was to review our experience in patients
      who underwent a carotid endarterectomy after medical treatment had failed, based
      on pathologic findings detected by carotid duplex ultrasound with minimal disease
      on arteriography. The medical records of 14 patients who underwent carotid
      endarterectomy for TIA symptoms related to ulcerated or irregular heterogeneous
      plaques were analyzed. All had had preoperative carotid duplex ultrasound,
      arteriography, and cardiac and neurologic workups to rule out other causes for
      their TIAs. Medical treatment had failed in all of them. There were 10 men and
      four women whose median age was 68 years. Carotid duplex ultrasound showed
      irregular heterogeneous carotid plaque in all patients associated with 20% to 50%
      stenosis in 12 and approximately 50% to 60% stenosis in two. All had normal to <
      20% stenosis on arteriograms. The duplex ultrasound findings were all confirmed
      at operation. All had an uneventful postoperative course with relief of symptoms.
      Carotid duplex ultrasound is superior to carotid arteriography in detecting
      irregular or ulcerative heterogeneous plaque associated with nonsignificant
      stenosis. Carotid duplex ultrasound can be used to determine the desirability of
      carotid endarterectomy after failed medical treatment in patients with classical
      and persistent TIA symptoms despite normal or minimal disease on arteriograms. A
      successful endarterectomy appears to predict an asymptomatic postoperative
      course.

PMID- 8879397
TI  - Bilateral chylothorax following thoracic duct ligation: case report and review of
      the literature.
AB  - Bilateral chylothorax following thoracic duct injury is a rare occurrence. Since
      1907 there have been only six reports in the literature of this potentially
      serious complication. We report a case of bilateral chylothorax following
      ligation of the cervical thoracic duct during a left subclavian to carotid artery
      transposition.

PMID- 8879398
TI  - Aortic aneurysm-induced disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (DIC) may result in hemorrhagic and
      thrombotic complications and is rarely associated with stable abdominal aortic
      aneurysms. In a retrospective review of our experience over the past 5 years, we
      identified only two instances of DIC-associated abdominal aortic aneurysms among
      a total of 67 patients who were operated on for asymptomatic aneurysms. In the
      first patient with DIC induced by abdominal aortic aneurysm, consumptive
      coagulopathy and a bleeding diathesis developed. The second patient's course was
      complicated by consumptive coagulopathy and migrating thrombophlebitis. In both
      instances coagulopathy resolved after surgical intervention. In this report we
      briefly discuss the pathogenesis and laboratory diagnosis of aneurysm-associated
      DIC and review current management strategies.

PMID- 8879399
TI  - Gerota's fascia flap: an alternative for aortic graft coverage.
AB  - The greater omentum is commonly used when there is a surgical indication for a
      barrier between an aortic graft and the abdominal contents. There are few other
      options when the omentum is not available. A novel approach is described for this
      purpose-Gerota's fascia flap. It is a simple, durable technique that can readily
      be used to provide extra tissue in the retroperitoneum for coverage of an aortic
      graft or possibly an aortic stump.

PMID- 8879400
TI  - Techniques in renal artery reconstruction: part II.

PMID- 8879401
TI  - Portal hypertension and bleeding esophagogastric varices.

PMID- 8879402
TI  - Biotechnology of lactic acid bacteria with special reference to bacteriophage
      resistance.
AB  - Lactic acid bacteria play an important role in many food and feed fermentations.
      In recent years major advances have been made in unravelling the genetic and
      molecular basis of significant industrial traits of lactic acid bacteria.
      Bacteriophages which can infect and destroy lactic acid bacteria pose a
      particularly serious threat to dairy fermentations that can result in serious
      economic losses. Consequently, these organisms and the mechanisms by which they
      interact with their hosts have received much research attention. This paper
      reviews some of the key discoveries over the years that have led us to our
      current understanding of bacteriophages themselves and the means by which their
      disruptive influence may be minimized.

PMID- 8879403
TI  - Biosynthesis of bacteriocins in lactic acid bacteria.
AB  - A large number of new bacteriocins in lactic acid bacteria (LAB) has been
      characterized in recent years. Most of the new bacteriocins belong to the class
      II bacteriocins which are small (30-100 amino acids) heat- stable and commonly
      not post-translationally modified. While most bacteriocin producers synthesize
      only one bacteriocin, it has been shown that several LAB produce multiple
      bacteriocins (2-3 bacteriocins). Based on common features, some of the class II
      bacteriocins can be divided into separate groups such as the pediocin-like and
      strong anti-listeria bacteriocins, the two-peptide bacteriocins, and bacteriocins
      with a sec-dependent signal sequence. With the exception of the very few
      bacteriocins containing a sec-dependent signal sequence, class II bacteriocins
      are synthesized in a preform containing an N-terminal double-glycine leader. The
      double-glycine leader-containing bacteriocins are processed concomitant with
      externalization by a dedicated ABC-transporter which has been shown to possess an
      N-terminal proteolytic domain. The production of some class II bacteriocins
      (plantaricins of Lactobacillus plantarum C11 and sakacin P of Lactobacillus sake)
      have been shown to be transcriptionally regulated through a signal transduction
      system which consists of three components: an induction factor (IF), histidine
      protein kinase (HK) and a response regulator (RR). An identical regulatory system
      is probably regulating the transcription of the sakacin A and carnobacteriocin B2
      operons. The regulation of bacteriocin production is unique, since the IF is a
      bacteriocin-like peptide with a double-glycine leader processed and externalized
      most probably by the dedicated ABC-transporter associated with the bacteriocin.
      However, IF is not constituting the bacteriocin activity of the bacterium, IF is
      only activating the transcription of the regulated class II bacteriocin gene(s).
      The present review discusses recent findings concerning biosynthesis, genetics,
      and regulation of class II bacteriocins.

PMID- 8879404
TI  - Inducible gene expression and environmentally regulated genes in lactic acid
      bacteria.
AB  - Relatively recently, a number of genes and operons have been identified in lactic
      acid bacteria that are inducible and respond to environmental factors. Some of
      these genes/operons had been isolated and analysed because of their importance in
      the fermentation industry and, consequently, their transcription was studied and
      found to be regulatable. Examples are the lactose operon, the operon for nisin
      production, and genes in the proteolytic pathway of Lactococcus lactis, as well
      as xylose metabolism in Lactobacillus pentosus. Some other operons were
      specifically targetted with the aim to compare their mode of regulation with
      known regulatory mechanisms in other well-studied bacteria. These studies,
      dealing with the biosynthesis of histidine, tryptophan, and of the branched chain
      amino acids in L. lactis, have given new insights in gene regulation and in the
      occurrence of auxotrophy in these bacteria. Also, nucleotide sequence analyses of
      a number of lactococcal bacteriophages was recently initiated to, among other
      things, specifically learn more about regulation of the phage life cycle. Yet
      another approach in the analysis of regulated genes is the 'random' selection of
      genetic elements that respond to environmental stimuli and the first of such
      sequences from lactic acid bacteria have been identified and characterized. The
      potential of these regulatory elements in fundamental research and practical
      (industrial) applications will be discussed.

PMID- 8879405
TI  - Lytic systems in lactic acid bacteria and their bacteriophages.
AB  - Lytic systems of lactic acid bacteria and their bacteriophages are reviewed with
      an emphasis on molecular characterization. Details of enzyme biochemistry and the
      cloning and analysis of lytic genes are presented, with coverage of lactococcal
      prolate headed bacteriophages, lactococcal isometric bacteriophages,
      Lactobacillus bacteriophages and lactococcal autolysins. Some comments on the
      importance of autolysis in cheese ripening are included and the biotechnological
      exploitation of cloned and characterized lytic genes is presented.

PMID- 8879406
TI  - Genomic organization of lactic acid bacteria.
AB  - Current knowledge of the genomes of the lactic acid bacteria, Lactococcus lactis
      and Streptococcus thermophilus, and members of the genera Lactobacillus,
      Leuconostoc, Pediococcus and Carnobacterium, is reviewed. The genomes contain a
      chromosome within the size range of 1.8 to 3.4 Mbp. Plasmids are common in
      Lactococcus lactis (most strains carry 4-7 different plasmids), some of the
      lactobacilli and pediococci, but they are not frequently present in S.
      thermophilus, Lactobacillus delbrueckii subsp. bulgaricus or the intestinal
      lactobacilli. Five IS elements have been found in L. lactis and most strains
      carry multiple copies of at least two of them; some strains also carry a 68-kbp
      conjugative transposon. IS elements have been found in the genera Lactobacillus
      and Leuconostoc, but not in S. thermophilus. Prophages are also a normal
      component of the L. lactis genome and lysogeny is common in the lactobacilli,
      however it appears to be rare in S. thermophilus. Physical and genetic maps for
      two L. lactis subsp. lactis strains, two L. lactis subsp. cremoris strains and S.
      thermophilus A054 have been constructed and each reveals the presence of six rrn
      operons clustered in less than 40% of the chromosome. The L. lactis subsp.
      cremoris MG1363 map contains 115 genetic loci and the S. thermophilus map has 35.
      The maps indicate significant plasticity in the L. lactis subsp. cremoris
      chromosome in the form of a number of inversions and translocations. The cause(s)
      of these rearrangements is (are) not known. A number of potentially powerful
      genetic tools designed to analyse the L. lactis genome have been constructed in
      recent years. These tools enable gene inactivation, gene replacement and gene
      recovery experiments to be readily carried out with this organism, and
      potentially with other lactic acid bacteria and Gram-positive bacteria.
      Integration vectors based on temperate phage attB sites and the random insertion
      of IS elements have also been developed for L. lactis and the intestinal
      lactobacilli. In addition, a L. lactis sex factor that mobilizes the chromosome
      in a manner reminiscent to that seen with Escherichia coli Hfr strains has been
      discovered and characterized. With the availability of this new technology,
      research into the genome of the lactic acid bacteria is poised to undertake a
      period of extremely rapid information accrual.

PMID- 8879407
TI  - The proteolytic systems of lactic acid bacteria.
AB  - Proteolysis in dairy lactic acid bacteria has been studied in great detail by
      genetic, biochemical and ultrastructural methods. From these studies the picture
      emerges that the proteolytic systems of lactococci and lactobacilli are
      remarkably similar in their components and mode of action. The proteolytic system
      consists of an extracellularly located serine-proteinase, transport systems
      specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of
      intracellular peptidases. This review describes the properties and regulation of
      individual components as well as studies that have led to identification of their
      cellular localization. Targeted mutational techniques developed in recent years
      have made it possible to investigate the role of individual and combinations of
      enzymes in vivo. Based on these results as well as in vitro studies of the
      enzymes and transporters, a model for the proteolytic pathway is proposed. The
      main features are: (i) proteinases have a broad specificity and are capable of
      releasing a large number of different oligopeptides, of which a large fraction
      falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is
      the main route for nitrogen entry into the cell; (iii) all peptidases are located
      intracellularly and concerted action of peptidases is required for complete
      degradation of accumulated peptides.

PMID- 8879409
TI  - Lactococcus lactis and stress.
AB  - It is now generally recognized that cell growth conditions in nature are often
      suboptimal compared to controlled conditions provided in the laboratory. Natural
      stresses like starvation and acidity are generated by cell growth itself. Other
      stresses like temperature or osmotic shock, or oxygen, are imposed by the
      environment. It is now clear that defense mechanisms to withstand different
      stresses must be present in all organisms. The exploration of stress responses in
      lactic acid bacteria has just begun. Several stress response genes have been
      revealed through homologies with known genes in other organisms. While stress
      response genes appear to be highly conserved, however, their regulation may not
      be. Thus, search of the regulation of stress response in lactic acid bacteria may
      reveal new regulatory circuits. The first part of this report addresses the
      available information on stress response in Lactococcus lactis. Acid stress
      response may be particularly important in lactic acid bacteria, whose growth and
      transition to stationary phase is accompanied by the production of lactic acid,
      which results in acidification of the media, arrest of cell multiplication, and
      possible cell death. The second part of this report will focus on progress made
      in acid stress response, particularly in L. lactis and on factors which may
      affect its regulation. Acid tolerance is presently under study in L. lactis. Our
      results with strain MG1363 show that it survives a lethal challenge at pH 4.0 if
      adapted briefly (5 to 15 minutes) at a pH between 4.5 and 6.5. Adaptation
      requires protein synthesis, indicating that acid conditions induce expression of
      newly synthesized genes. These results show that L. lactis possesses an inducible
      response to acid stress in exponential phase. To identify possible regulatory
      genes involved in acid stress response, we determined low pH conditions in which
      MG1363 is unable to grow, and selected at 37 degrees C for transposition
      insertional mutants which were able to survive. About thirty mutants resistant to
      low pH conditions were characterized. The interrupted genes were identified by
      sequence homology with known genes. One insertion interrupts ahrC, the putative
      regulator of arginine metabolism; possibly, increased arginine catabolism in the
      mutant produces metabolites which increase the pH. Several other mutations
      putatively map at some step in the pathway of (p)ppGpp synthesis. Our results
      suggest that the stringent response pathway, which is involved in starvation and
      stationary phase survival, may also be implicated in acid pH tolerance.

PMID- 8879410
TI  - Physiology of pyruvate metabolism in Lactococcus lactis.
AB  - Lactococcus lactis, a homofermentative lactic acid bacterium, has been studied
      extensively over several decades to obtain sometimes conflicting concepts
      relating to the growth behaviour. In this review some of the data will be
      examined with respect to pyruvate metabolism. It will be demonstrated that the
      metabolic transformation of pyruvate can be predicted if the growth-limiting
      constraints are adequately established. In general lactate remains the major
      product under conditions in which sugar metabolism via a homolactic fermentation
      can satisfy the energy requirements necessary to assimilate anabolic substrates
      from the medium. In contrast, alternative pathways are involved when this energy
      supply becomes limiting or when the normal pathways can no longer maintain
      balanced carbon flux. Pyruvate occupies an important position within the
      metabolic network of L. lactis and the control of pyruvate distribution within
      the various pathways is subject to co-ordinated regulation by both gene
      expression mechanisms and allosteric modulation of enzyme activity.

PMID- 8879408
TI  - Metabolic engineering of sugar catabolism in lactic acid bacteria.
AB  - Lactic acid bacteria are characterized by a relatively simple sugar fermentation
      pathway that, by definition, results in the formation of lactic acid. The
      extensive knowledge of traditional pathways and the accumulating genetic
      information on these and novel ones, allows for the rerouting of metabolic
      processes in lactic acid bacteria by physiological approaches, genetic methods,
      or a combination of these two. This review will discuss past and present examples
      and future possibilities of metabolic engineering of lactic acid bacteria for the
      production of important compounds, including lactic and other acids, flavor
      compounds, and exopolysaccharides.

PMID- 8879411
TI  - Acceleration of cheese ripening.
AB  - The characteristic aroma, flavour and texture of cheese develop during ripening
      of the cheese curd through the action of numerous enzymes derived from the cheese
      milk, the coagulant, starter and non-starter bacteria. Ripening is a slow and
      consequently an expensive process that is not fully predictable or controllable.
      Consequently, there are economic and possibly technological incentives to
      accelerate ripening. The principal methods by which this may be achieved are: an
      elevated ripening temperature, modified starters, exogenous enzymes and cheese
      slurries. The advantages, limitations, technical feasibility and commercial
      potential of these methods are discussed and compared.

PMID- 8879412
TI  - Barriers to application of genetically modified lactic acid bacteria.
AB  - To increase the acceptability of food products containing genetically modified
      microorganisms it is necessary to provide in an early stage to the consumers that
      the product is safe and that the product provide a clear benefit to the consumer.
      To comply with the first requirement a systematic approach to analyze the
      probability that genetically modified lactic acid bacteria will transform other
      inhabitants of the gastro- intestinal (G/I) tract or that these lactic acid
      bacteria will pick up genetic information of these inhabitants has been proposed
      and worked out to some degree. From this analysis it is clear that reliable data
      are still missing to carry out complete risk assessment. However, on the basis of
      present knowledge, lactic acid bacteria containing conjugative plasmids should be
      avoided. Various studies show that consumers in developed countries will accept
      these products when they offer to them health or taste benefits or a better
      keepability. For the developing countries the biggest challenge for scientists is
      most likely to make indigenous fermented food products with strongly improved
      microbiological stability due to broad spectra bacteriocins produced by lactic
      acid bacteria. Moreover, these lactic acid bacteria may contribute to health.

PMID- 8879413
TI  - Lactic acid bacteria as vaccine delivery vehicles.

PMID- 8879415
TI  - Consumers' views on food quality. A qualitative interview study.
AB  - The study investigated the themes consumers discuss when describing their
      everyday considerations about food quality. Twenty Copenhagen families with young
      children were interviewed open-endedly concerning daily food-related practices
      and thoughts, making particular use of narrative descriptions of specific meals.
      Respondents expressed both positive and negative opinions about a broad variety
      of processed and unprocessed foods. Positive opinions about food quality related
      mainly to personal criteria such as taste or convenience. Negative comments
      mainly related to how foods were processed or distributed. The study suggests
      that concerns about food safety are integrated in everyday concepts of food
      quality, and that consumers individually develop strategies to deal with this.
      However, feelings of uncertainty, helplessness and self reproach were frequently
      reported. The results suggest that choices of foods often reflect compromises in
      everyday life rather than the consumers' preferences.

PMID- 8879416
TI  - Salivary reactivity in restrained and unrestrained eaters and women with bulimia
      nervosa.
AB  - Salivary and cognitive reactivity to a highly palatable food cue were examined in
      19 women with bulimia nervosa, 19 restained eaters and 19 unrestrained eaters.
      Salivary reactivity at presentation of the palatable food varied significantly
      across the three groups but not baseline. Bulimic women displayed significantly
      less salivary reactivity than either restrained or unrestrained eaters. Bulimic
      women were depressed and self-reported markedly greater anxiety (SUDS) at all
      points during the procedure. SUDS were not significantly correlated with salivary
      reactivity. Depression as measured by the Beck Depression Inventory was
      significantly and inversely correlated with salivary reactivity. Potential
      cognitive and physiological explanations for decreased salivary reactivity in
      women with bulimia are discussed.

PMID- 8879414
TI  - Biopreservation by lactic acid bacteria.
AB  - Biopreservation refers to extended storage life and enhanced safety of foods
      using the natural microflora and (or) their antibacterial products. Lactic acid
      bacteria have a major potential for use in biopreservation because they are safe
      to consume and during storage they naturally dominate the microflora of many
      foods. In milk, brined vegetables, many cereal products and meats with added
      carbohydrate, the growth of lactic acid bacteria produces a new food product. In
      raw meats and fish that are chill stored under vacuum or in an environment with
      elevated carbon dioxide concentration, the lactic acid bacteria become the
      dominant population and preserve the meat with a "hidden' fermentation. The same
      applies to processed meats provided that the lactic acid bacteria survive the
      heat treatment or they are inoculated onto the product after heat treatment. This
      paper reviews the current status and potential for controlled biopreservation of
      foods.

PMID- 8879417
TI  - The effect of social setting on response to a preloading manipulation in non
      obese women and men.
AB  - To determine the effect of a social setting on the physiological controls of
      eating, four pairs of subjects consumed a 15% and a 1% glucose (sweetened with
      aspartame to match the 15%) preload drink, preceding a test lunch meal,
      individually in a laboratory, and as a pair in a cafeteria. Compared with the 1%
      glucose preload, the 15% glucose preload significantly reduced food intake by the
      same amount in both settings (mean meal intakes: 467.4 g vs. 610.2 g,
      respectively). Intakes were 141.3 g +/- 41.8 SED less after the 15% than the 1%
      preload in the laboratory setting (t28df = 3.38, p = 0.0022), and 144.2 g +/-
      41.8 SED in the cafeteria setting (t28df = 3.45, p = 0.0018). This result
      suggests that different social settings do not significantly alter physiological
      satiety cues and demonstrates that at least one of the physiological controls of
      eating, that has been tested in a laboratory setting, is reproducible in a
      cafeteria setting.

PMID- 8879418
TI  - Reinforcing value of food in obese and non-obese women.
AB  - Food is a powerful reinforcer, and individual differences in the reinforcing
      efficacy of food may provide a mechanism to explain the excess intake and
      positive energy balance responsible for obesity. The present study tested the
      hypothesis that eating palatable food would be more reinforcing than engaging in
      sedentary activities (e.g. playing computer games) for obese in comparison to non
      obese non-dietary restrained female college students. Subjects could choose to
      eat food or engage in sedentary activities based on their responding in a
      computer-generated concurrent schedules task. The reinforcement schedule
      associated with earning access to sedentary activities was held at variable ratio
      2 (VR2) while the food reinforcement schedule was set at VR2 in the first trial
      of the choice task and doubled across the four subsequent trials from VR4 to
      VR32. Choice and consumption results indicated that eating was significantly more
      reinforcing than engaging in sedentary activities for obese subjects than non
      obese subjects. Hedonics for the activities and foods were not correlated with
      total food reinforcers earned and did not differ between the groups. These
      results confirm the hypothesis that eating food is more reinforcing than selected
      alternative activities to a greater extent for obese than for non-obese young
      women.

PMID- 8879419
TI  - Diet and physical activity in restrained eaters.
AB  - Food choices, nutrient intakes, activity patterns and restrained eating scores
      were obtained from 249 normal-weight, young adults using self-reported
      questionnaires. Restrained eaters reported that they consumed more fat-free dairy
      products, fewer full-fat dairy products, fewer servings of fats and oils, less
      red meat and more fruits and vegetables than unrestrained eaters. In contrast to
      previous research, we found no overall difference in estimated daily energy
      intakes between restrained and unrestrained eaters, although there was a strong
      trend for restrained men to consume fewer calories per day. However, restrained
      eaters consumed less fat and more carbohydrate than unrestrained eaters.
      Restrained eaters in general were not more physically active than unrestrained
      eaters, but among the most active women, the restrained eaters were estimated to
      consume 13.3% less fat then the unrestrained eaters. This relationship was not
      observed in men. These data suggest that: (1) restrained eating influenced
      macronutrient composition in our respondents, but these effects were somewhat
      different in men and women; and (2) exercise played an important role in the
      dieting practices of restrained women but not restrained men. Examining only the
      food intakes of restrained women without considering their physical activity
      patterns may provide an incomplete picture of their dieting strategies.

PMID- 8879420
TI  - Increased liking for salty foods in adolescents exposed during infancy to a
      chloride-deficient feeding formula.
AB  - In a model selected for its similarity to the hormonal consequences of sodium
      deficiency, food choices of 169 adolescents exposed during infancy to a chloride
      deficient feeding formula were compared to those of their closest-aged siblings.
      Questionnaires completed by parents were used to assess food likes and dislikes.
      When a salty food was mentioned by parents as one craved by either child, exposed
      children were more likely than siblings to crave that food (p = 0.005).
      Frequencies of two of four salt-related dietary behaviors [adding salt to food
      before tasting (p = 0.03) and to atypical foods (p = 0.05)] were higher in
      exposed adolescents than in siblings, while frequencies of parallel sugar-related
      behaviors did not differ between the groups. Foods classified as being lower in
      saltiness were disliked by exposed children relative to siblings (p = 0.003),
      although ratings of foods higher in saltiness did not differ. Finally, when asked
      to rank eight foods in order of preference, ranks assigned by exposed children to
      salty foods tended (p = 0.07) to be higher than those of siblings. The data
      suggest a persistent effect of early experience on human salt preference.
      Additional studies are needed to determine whether salt intake is increased in
      this and other populations that suffer electrolyte depletion during early
      development.

PMID- 8879421
TI  - Duodenogastric reflux of intestinal infusions in rats is volume dependent.
AB  - Experiments employing infusions of nutrients into the gastrointestinal tract
      commonly deliver large volumes of solutions without evaluating the possibility
      that reflux of the infusate to more orad sites may occur. To assess this
      possibility for one conventional paradigm, rats with gastric fistulas and
      intestinal catheters were infused intraduodenally (4.0 to 5.0 cm distal to
      pylorus) in association with a meal. Infusions of 0.0 ml to 15.0 ml of 3% glucose
      and a dye marker or 0.9% saline containing a dye marker were delivered at 1
      ml/min, and stomach contents were assayed for the infusates. All three probes
      were detected in stomach contents. The glucose marker proved the most sensitive
      of the three and indicated that duodenogastric reflux occurred in a dose
      dependent manner with infusions > 2.5 ml.

PMID- 8879422
TI  - Resuscitation with increasing doses of diaspirin crosslinked hemoglobin in swine.
AB  - This study examined the effects of administering 0.5, 4, 10, and 30 mL/kg of
      Diaspirin Crosslinked Hemoglobin (DCLHb) in a swine model of non-lethal
      hemorrhagic shock. Thirty unanesthetized animals were bled (30 mL/kg, 1
      mL/kg/min) and either recovered without treatment (Untreated Control, UC) or
      infused with 10 g/dL DCLHb (0.5, 4.0, 10 or 30 mL/kg at 1 mL/kg/min) or Lactated
      Ringer (LR, 90 mL/kg at 3 mL/kg/min). DCLHb caused dose-related increases in MAP.
      Both the 10 and 30 mL/kg doses of DCLHb increased MAP more than UC or LR. Lower
      doses of DCLHb and LR had effects on MAP similar to UC. After hemorrhage, CO
      increased in all groups. The effect of DCLHb on CO was dose-related. Only LR and
      30 mL/kg of DCLHb transiently (through 90 min) increased CO more than UC. CO in
      animals given lower doses of DCLHb was comparable to UC. DCLHb (10 and 30 mL/kg)
      improved base excess and lactate concentrations, two indices of global perfusion,
      more rapidly and to a greater extent than either UC or LR. In this swine model of
      hemorrhage, even small doses of DCLHb exerted measurable beneficial effects on
      blood pressure and perfusion.

PMID- 8879423
TI  - Characterization of coffea canephora alpha-D-galactosidase blood group B
      activity.
AB  - Enzymatic conversion of type B to O erythrocytes with Coffea (coffee bean) alpha
      D-galactosidase was first described by Harpaz and Flowers and subsequently
      adopted by others (1,2). An enzyme-linked immunosorbent assay (ELISA) and soluble
      oligosaccharide substrates were used to study deantigenation of B erythrocytes
      with the Coffea enzyme. For the ELISA, microtiter wells were coated with B
      membranes and treated with enzyme under a variety of conditions, probed with
      primary IgM monoclonal anti-B followed by secondary anti-murine mu-chain specific
      alkaline phosphatase conjugate, then developed with substrate. This technique has
      allowed the rapid determination of enzymatic activity over a broad range of
      conditions; the purpose being to determine parameters for efficiently enhancing
      enzyme activity. Solid phase activity was then compared to activity against
      soluble oligosaccharide substrates. We have determined that, under the conditions
      tested, only moderate increases in enzyme activity against the B epitope can be
      achieved by modifying reaction conditions with the native Coffea enzyme.

PMID- 8879424
TI  - Decreased agglutinability of methoxy-polyethylene glycol attached red blood
      cells: significance as a blood substitute.
AB  - Human Rb(+) AB type red blood cells were modified with methoxy-polyethylene
      glycol (mPEG) in order to decrease agglutinabilities toward clinically important
      anti-A, anti-B and anti-D reagents. Attachment of mPEG to membrane proteins of
      the red blood cell was identified by the shift of well-known blood group active
      glycoprotein bands such as band 3, 4.5 and PAS-1 on the SDS-polyacrylamide gel
      electrophoresis. When 4mM concentration of mPEG was added to red blood cells,
      agglutination was minimum by a blood group typing and microwell agglutination
      tests. Antibody binding tests showed decreased antibody binding to blood group
      antigens after mPEG attachment. The decrease of both agglutinability and antibody
      binding was the result of mPEG attachment to blood group active glycoprotein of
      the cell membrane. The morphology of red blood cells after mPEG attachment was
      the usual discocytic cell. Oxygen equilibrium curves of the mPEG-attached red
      blood cells were similar to unmodified red blood cells. This approach to decrease
      agglutinability of the red blood cells toward blood group antibodies may be used
      to develop a universally transfusible blood substitute.

PMID- 8879425
TI  - Enhancement of erythrocyte sedimentation rate by polymerized hemoglobin.
AB  - Development of hemoglobin-based blood substitutes requires the scrutiny of blood
      rheological parameters that could be influenced by this class of molecules.
      Accordingly, we have examined the effects of glutaraldehyde-polymerized human
      hemoglobin on the erythrocyte sedimentation rate (ESR). For this purpose, human
      hemoglobin (Hb) was polymerized by glutaraldehyde, and its progress was monitored
      by gel permeation. ESR was measured by addition of hemoglobin or polymerized Hb
      (Poly-Hb) to citrated rat whole blood. The results indicate that, whereas Hb
      exerted minimal perturbation of ESR, Poly-Hb obtained under some polymerization
      conditions induced an over fifty-fold elevation of ESR. When polymerized Hb was
      fractionated by size, and different fractions were tested for their effects on
      ESR, a sharp dependence of ESR enhancement on molecular size of polymerized Hb
      was found. These observations suggest that ESR enhancement is mediated by
      macromolecular bridging formed by Poly-Hb of an adequate length between the
      surfaces of two stacking erythrocytes.

PMID- 8879426
TI  - Imaging of liposomes by scanning tunneling microscopy.
AB  - In this study, unilamellar and multilamellar liposomes consisting of
      dipalmitoylphosphatidylcholine, cholesterol and dicetylphosphate were prepared.
      Scanning tunneling microscopy images of these liposomes on highly oriented
      pyrolytic graphite surfaces were obtained. It was observed that scanning
      tunnelling microscopy can be successfully used for high-resolution, three
      dimensional structure analysis of liposomes under very mild conditions.

PMID- 8879427
TI  - The cytotoxic activities of human hemoglobin and diaspirin crosslinked
      hemoglobin.
AB  - It is well known that hemoglobin (Hb) possesses many oxidative enzyme activities,
      including a pseudo-peroxidase activity. It has also been shown by many
      investigators that various peroxidases in the presence of hydrogen peroxide and a
      halide ion exert a potent cytotoxic activity toward various mammalian cell types.
      It has further been observed by various investigators that the administration of
      relatively large amounts of purified Hb or a Hb derivative to a host animal
      during resuscitation experiments leads to a number of unrelated types of tissue
      damage and cell damage in the host. The first objective of this investigation was
      to determine if the observed tissue and cell damage may be due to a cytotoxic
      activity that Hb may exert in vivo analogous to that of the peroxidases. We also
      showed some time ago that peroxidases are able to activate peritoneal macrophages
      to the cytocidal state. Hence, we also addressed the question whether or not Hb
      is able to activate macrophages in a similar manner. Our results were negative
      with regard to both questions. Further investigations indicated that, unlike the
      peroxidases, ferryl-Hb is unable to oxidize iodide to iodine at a measurable
      rate, which appears to be the reason for the lack of cytotoxic activity.

PMID- 8879428
TI  - Kinetic properties of glucosyltransferase adsorbed onto saliva-coated
      hydroxyapatite.
AB  - Results from previous studies have shown that several properties of
      glucosyltransferase (GTF) adsorbed onto saliva-coated hydroxyapatite beads differ
      from those of GTF in solution. For example: thermostability, pH-activity
      dependency, sensitivity to inhibitors. The aim of this study was to compare the
      kinetics of the adsorbed GTF with its kinetic properties in solution.
      Hydroxyapatite beads were coated with human parotid saliva (sHA). Following
      washes, cell-free GTF enzyme from Streptococcus sobrinus 6715 (S. sobrinus 6715)
      or Streptococcus mutans GS-5 (S. mutans GS-5) was adsorbed onto sHA. The GTF
      coated sHA were then incubated with radiolabeled sucrose for intervals of 5-360
      minutes and the amount of glucans synthesized in situ by the adsorbed GTF was
      determined and compared with that produced in solution. The adsorbed GTF (from S.
      sobrinus 6715) exhibited a sharp increase in glucan production within the first 5
      minutes of incubation while surface-bound GTF of S. mutans GS-5 displayed an
      initial burst of activity within the first 15 minutes of incubation. During the
      next 6 hours (duration of experiment) the amount of glucan on the beads did not
      increase with either enzyme. In contrast, the kinetic profile of the two GTFs in
      solution demonstrated a linear increase in the amount of glucans formed, with no
      initial burst effect. The results indicate that the rapid formation of glucans by
      GTF adsorbed onto sHA could have implications for colonization by oral
      microorganisms on tooth surfaces. The accelerated synthesis of glucan on tooth
      surfaces may affect the microbiology of the dental plaque, and might also
      influence the movement of substances, such as acids and antiplaque agents, across
      the acquired pellicle and dental plaque.

PMID- 8879429
TI  - Interleukin-2 receptor-specific fusion toxin inhibits barotrauma-induced arterial
      atherosclerosis.
AB  - Immunocytochemical analyses of human plaques and experimental arterial lesions
      have implicated activated lymphocytes and monocytes in the pathogenesis of
      atherosclerosis, as demonstrated by the expression of interleukin-2 (IL-2)
      membrane receptors and major histocompatibility complex class II epitopes. The
      objective is to determine if targeting these cells with an IL-2 receptor-specific
      chimeric toxin, DAB486-IL-2, can inhibit experimental post-angioplasty vascular
      neointimal thickening. Twenty-two atherogenically modeled rabbits were treated in
      vivo with DAB486-IL-2 (0.1 mg/kg per day i.v.; n = 11) or placebo (n = 11) for 10
      days following aortic balloon angioplasty (4 atm x 30 s each x 2 dilatations). In
      vitro 3H-leucine incorporation studies of mononuclear leukocyte and vascular
      smooth muscle cell protein synthesis inhibition by DAB486-IL-2 were also
      performed. Angioplasty sites were examined for evidence of hyperproliferative
      atherosclerotic narrowing by quantitative angiography and histomorphometry of
      neointimal cross-sectional area at baseline and 6 weeks after injury. In vitro
      Concanavalin-A stimulated rabbit mononuclear leukocyte protein synthesis was 50%
      inhibited by DAB486-IL-2 at a concentration (IC50) of 6 x 10(-11) M. Rabbit
      vascular smooth muscle cells were approximately 150-fold less sensitive to DAB486
      IL-2 (IC50 = 10(-8) M). In vivo studies showed no change in angioplasty site
      angiographic minimum luminal diameter at 6 weeks in DAB486-IL-2 treated animals
      (from 2.96 +/- 0.52 to 2.96 +/- 0.48 mm; percent cross-sectional area reduction =
      1 +/- 10%; P = N.S.). In control animals, luminal diameter decreased from 2.79 +/
      0.4 to 2.32 +/- 0.52 mm at 6 weeks, and percent cross-sectional area was reduced
      by 34 +/- 14% (P < 0.01 vs. placebo). Quantitative histomorphometric angioplasty
      segmental intimal cross-sectional area reduction of treated and placebo vessels
      also differed significantly (19 +/- 16% vs. 31 +/- 21%; P < 0.05). DAB486-IL-2
      caused no adverse effects on animal survival, weight or hepatic transaminase
      levels. We conclude that post-angioplasty administration of the chimeric toxin
      DAB486-IL-2 inhibits angiographic narrowing and neointimal thickening in the
      atherogenic rabbit model. Although this IL-2 receptor-specific molecule was
      cytotoxic in vitro for activated mononuclear leukocytes and vascular smooth
      muscle cells, systemic toxicity did not occur in vivo at a dose comparable to
      that evaluated in clinical trials of this agent. Potential anti-proliferative
      effects of this chimeric toxin may be mediated by direct local inhibition of
      leukocyte-mediated inflammation, or through the indirect modification of vascular
      cell mitogenesis and cytokine release.

PMID- 8879430
TI  - Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery
      disease.
AB  - Chylomicron catabolism in the bloodstream consists of lipolysis by lipoprotein
      lipase and uptake of remnants by the liver. In rats, triglyceride-rich emulsions
      can mimic chylomicron metabolism. To further validate this model in man, the
      emulsion was injected intravenously into fasting and into subjects previously fed
      a test fatty meal. The plasma kinetic curves of the emulsion 3H-triglyceride and
      14C-cholesteryl ester were determined. The fractional clearance rate (FCR) of
      both labels was markedly reduced in the fed subjects (triglycerides: fed = 0.018
      +/- 0.007; fasting = 0.105 +/- 0.013 min-1, P < 0.001; cholesteryl ester: fed =
      0.016 +/- 0.001; fasting = 0.040 +/- 0.006 min-1; P < 0.05) indicating that the
      emulsion and chylomicrons generated from the testinal lipid absorption compete
      for the same catabolic processes, confirming the validity of the method. The
      emulsion was injected into 11 patients with CAD and into 11 controls. All had
      plasma cholesterol < 240 and triglycerides < 250 mg/dl. FCR of triglycerides was
      5-fold smaller in CAD compared to controls (0.028 +/- 0.004 and 0.141 +/- 0.069
      min-1, respectively, P < 0.01). FCR of cholesteryl ester was 4-fold smaller in
      CAD than in controls (0.015 +/- 0.004 and 0.056 +/- 0.067 min-1 respectively, P <
      0.05). These results indicate that both chylomicron lipolysis and remnant removal
      are diminished in CAD.

PMID- 8879431
TI  - Plasma homocyst(e)ine levels and graded risk for myocardial infarction: findings
      in two populations at contrasting risk for coronary heart disease.
AB  - Standardized mortality rates for coronary heart disease (CHD) in men are about 3
      fold higher in Northern Ireland than in France. The differences could not be
      explained by the presence of conventional risk factors for atherosclerosis. We
      studied in subjects from these two countries, an additional risk factor, namely,
      concentration of plasma homocyst(e)ine which is frequently elevated in patients
      with CHD. We measured the plasma concentration of homocyst(e)ine in survivors of
      myocardial infarction (MI) and in control subjects from the Belfast, Strasbourg
      and Lille regions. Plasma homocyst(e)ine levels were higher in the Irish than in
      the French controls; subjects with MI had higher levels than controls. Results
      were compatible with global excess of risk for MI being graded across the
      distribution of plasma homocyst(e)ine concentrations, although the trends lost
      significance in Belfast after adjustment for other risk factors. The higher
      plasma homocyst(e)ine concentrations we observed in the Irish population could be
      the reason for the different CHD mortality rates. This epidemiological
      observation could prompt dietary and vitamin supplementation studies aimed at
      decreasing homocyst(e)ine levels as well as the incidence of arterial occlusive
      disease, under controlled conditions in high risk populations.

PMID- 8879432
TI  - Quantitative effects of the apolipoprotein E polymorphism in a biracial sample of
      9-10-year-old girls.
AB  - Genetic polymorphism at the apolipoprotein E locus (APOE) has been shown to have
      a significant impact on quantitative risk factors for coronary artery disease
      (CAD) in diverse populations. However, despite the recognition that
      atherosclerosis begins in childhood and that genetic factors are related to the
      initial stages of atherosclerosis, prior studies were carried out mostly on
      adults and little attention has been paid to genetic risk factors for CAD in
      children. We have examined the impact of APOE polymorphism on quantitative risk
      factors for CAD (apoAI, apoB, TC, LDL-C, HDL-C and TG) in a sample of 647 African
      American and 573 White 9-10-year-old girls who were enrolled in the National
      Heart, Lung and Blood Institute Growth and Healthy Study. The frequencies of the
      APOE*2, APOE*3 and APOE*4 alleles were 0.09, 0.76 and 0.15 in Whites and 0.11,
      0.70 and 0.19 in African Americans, respectively. The APOE*2 allele was
      significantly associated with lower mean levels of LDL-C and apoB and the APOE*4
      allele with higher levels of LDL-C and apoB in both racial groups. Variation in
      maturation stage, body fat and fat patterning, as assessed by skin fold measures
      and waist/hip ratio, accounted for a significant proportion of the variation in
      quantitative CAD risk factors.

PMID- 8879433
TI  - Effects of vitamin E on endothelium-dependent coronary flow in
      hypercholesterolemic dogs.
AB  - The authors studied the effect of vitamin E on endothelium-dependent coronary
      flow in hypercholesterolemic dogs. Adult mongrel dogs weighing 7.4 +/- 1.0 kg
      were divided into control, hypercholesterolemic and vitamin E groups. The animals
      in the hypercholesterolemic group were fed a diet enriched with cholesterol (5%
      w/w) and coconut oil (10% w/w) for 40 days. The vitamin E group received the same
      diet plus 400 IU of vitamin E during the last 15 days of the experiment. Total
      serum cholesterol levels were evaluated at the beginning and at the end of the
      experiment using a commercial enzyme kit and a Beckman analyzer. The coronary
      flow was determined by electromagnetic flowmetry using a probe positioned in the
      left anterior descending coronary artery, near the ostium. A needle connected to
      a perfusion pump was introduced into the coronary artery for the administration
      of acetylcholine and sodium nitroprusside at a rate of 5 micrograms/kg per min.
      The aorta was cannulated for the measurement of arterial blood pressure via a
      pressure transducer coupled to a Siemens multi-channel recorder. The tissue
      cholesterol content and malonic dialdehyde (MDA) were also measured in isolated
      coronary vessel specimens. At the end of 40 days, the serum cholesterol levels
      had increased by 226% and 190% in the hypercholesterolemic and vitamin E groups,
      respectively. However, the difference in the levels of these two groups was not
      significant (P > 0.05). The aortic blood pressure and heart rate remained
      unchanged during acetylcholine administration. In contrast, systolic and
      diastolic pressure fell and the heart rate increased during the infusion of
      sodium nitroprusside. The tissue cholesterol content and MDA were significantly
      (P < 0.05) increased in coronary artery specimens from the hypercholesterolemic
      compared to control animals. Vitamin E was able to reduce these increases in
      cholesterol treated animals (P < 0.05). The percent change in coronary flow
      during acetylcholine administration was significantly lower in the
      hypercholesterolemic group when compared with control animals (P < 0.05) but was
      unaltered in the vitamin E group (P > 0.05). During sodium nitroprusside
      administration, the coronary flow increased in the vitamin E group (P < 0.05).
      The authors conclude that hypercholesterolemia reduces endothelium-dependent
      coronary flow and increases the tissue cholesterol content and MDA of coronary
      arteries. Vitamin E decreases the MDA and the tissue cholesterol content without
      significantly affecting the total serum cholesterol level. Vitamin E may thus
      restore coronary flow by reverting endothelial dysfunction.

PMID- 8879434
TI  - Demonstration of potent lipid-lowering activity by a thyromimetic agent devoid of
      cardiovascular and thermogenic effects.
AB  - A potent lipid-lowering thyromimetic (CGS 26214) devoid of cardiac and
      thermogenic activity was identified based on its ability to preferentially access
      and bind the nuclear fraction of hepatocytes over that of myocytes in culture.
      The difference in access achieved with CGS 26214 was at least 100-fold better for
      hepatocytes than for myocytes. This in vitro hepatoselectivity resulted in a
      compound with unprecedented in vivo lipid-lowering potency with a minimal
      effective dose of 1 microgram/kg in rats and dogs (approximately 25x that of L
      T3). At the same time, CGS 26214 was free of any cardiovascular effects up to the
      highest dose tested of 25 mg/kg and 100 micrograms/kg in rats and dogs,
      respectively.

PMID- 8879435
TI  - Inhibition of LDL oxidation and myeloperoxidase dependent tyrosyl radical
      formation by the selective estrogen receptor modulator raloxifene (LY139481 HCL).
AB  - Cellular oxidation of protein and lipoproteins is believed to contribute to the
      pathology associated with both acute and chronic inflammatory processes.
      Enzymatic, myeloperoxidase and lipoxygenase, and non- enzymatic oxidation of low
      density lipoprotein, LDL, has been implicated in foam cell formation and the
      progression of atherosclerotic changes within the arterial wall. In the present
      study, the in vitro protective role of the selective estrogen receptor modulator,
      raloxifene, in these oxidant triggered processes has been investigated.
      Raloxifene, as with estrogen was observed to inhibit both copper mediated LDL
      oxidation as well as the cellular modification of LDL by murine peritoneal
      macrophages. Raloxifene was, however, a more potent inhibitor of LDL oxidation
      than 17 beta-estradiol. The inhibition of macrophage LDL modification by
      raloxifene was not due to a non-specific effect on all effector functions as
      phagocytosis of opsonized yeast was comparable with control macrophage cultures.
      In addition to the protective effects on LDL oxidation, raloxifene also inhibited
      tyrosyl radical formation catalyzed by myeloperoxidase. The inhibition of
      myeloperoxidase activity was observed for both the isolated enzyme and in phorbol
      ester stimulated murine peritoneal neutrophils. In contrast, raloxifene was a
      weaker inhibitor of horseradish peroxidase. These results demonstrate a potential
      protective role for raloxifene as an anti-oxidant in in vitro assays designed to
      evaluate oxidant mediated radical formation and tissue damage.

PMID- 8879436
TI  - Effects of postmenopausal hormone replacement therapy on lipoproteins including
      lipoprotein(a) and LDL subfractions.
AB  - The purpose of this study was to examine the effects on lipoprotein risk markers
      for CHD of oestradiol given alone and in combination with the androgenic
      progestogen, norethisterone. Eighty postmenopausal women were randomly allocated
      to receive oestradiol (2 mg/day) alone or with continuous norethisterone (1
      mg/day). Serum lipoprotein levels, including lipoprotein(a), were monitored
      during 12 months on treatment in all the women, and in a sub-set of 32 patients
      cholesterol was measured in the two major density subfractions of LDL. Oestradiol
      caused a transient rise in triglycerides, a small decrease in LDL cholesterol
      (significant only at 3 and 6 months, P < 0.05) and a consistent significant
      increase in HDL cholesterol (16%, P < 0.01). There was a downward trend in
      lipoprotein(a) levels which did not achieve statistical significance. The
      combined preparation caused significant, sustained decreases in triglycerides
      (31%, P < 0.01), total cholesterol (15%, P < 0.001), VLDL (42%, P < 0.01), LDL
      (9%, P < 0.05) and HDL (11%, P < 0.001). Lipoprotein(a) was also reduced (39%, P
      < 0.05). In the sub-set of patients in which LDL subfractions were measured, the
      reduction in LDL induced by oestradiol monotherapy was significant only at the 3
      month visit (6%, P < 0.05). This was due to a decrease in the 'light' (1.025 < d
      < 1.044 g/ml) subfraction (10%, P < 0.05) and resulted in an apparent shift in
      subfraction distribution towards the 'heavy' (1.044 < d < 1.060 g/ml)
      subfraction, although there was no absolute increase in the latter. None of these
      changes was statistically significant at 12 months. Oestradiol/norethisterone
      caused sustained decreases in both 'light' (15%, P < 0.05) and 'heavy' (29%, P <
      0.05) subfractions, with no significant change in the relative amounts. The
      changes in 'light' and 'heavy' LDL in this group were highly correlated with
      changes in triglyceride levels (r = -0.57, P < 0.05 and r = 0.82, P < 0.01
      respectively). Therefore, at the end of 1 year's treatment with unopposed
      oestradiol the only statistically significant change was an increase in HDL
      cholesterol. Addition of norethisterone to the preparation reversed this
      potentially beneficial change, but favourably influenced triglycerides, VLDL, LDL
      subfraction profile and lipoprotein(a), which may counteract the adverse effect
      on HDL.

PMID- 8879437
TI  - Properties of low density lipoproteins relevant to oxidative modifications change
      paradoxically during aging.
AB  - Atherosclerosis is a common problem among the elderly. Because lipid peroxidation
      is considered a contributor to the development of atherosclerosis, we compared
      oxidative properties of lipoproteins in an otherwise healthy (SENIEUR-classified)
      aged population (65-74 years) with young controls (18-30 years). Relative amounts
      of oxidatively altered low density lipoprotein (LDL), estimated by means of an
      antibody against LDL modified by 4-hydroxynonenal, a product of lipid
      peroxidation, were increased marginally in serum from the elderly (9.8 vs. 7.4%,
      P = 0.07). In contrast, isolated LDL from the elderly revealed a decreased
      susceptibility to in vitro oxidation: the lag time was increased (2.34 vs. 2.10
      h, P < 0.01), and the maximal rate of LDL oxidation decreased (0.88 vs. 1.01
      O.D./h, P = 0.001). However, there were no age-related changes in lipid
      composition of native LDL and consumption of fatty acids during in vitro
      oxidation. The serum concentrations of ascorbic acid and most lipophilic anti
      oxidants (the latter expressed per g serum lipids) were significantly decreased
      in the elderly except tocopherols which tended to be higher. In conclusion, our
      data reveal paradox age-related alterations of LDL as to its behaviour in
      oxidation in vivo vs. in vitro.

PMID- 8879438
TI  - Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in rabbit aortic
      neointima after selective de-endothelialization.
AB  - Altered TIMP-1 synthesis in the arterial wall may be important for the balance
      between metalloproteinases and their inhibitors, and thus contribute to
      dysregulated extracellular matrix metabolism in atherosclerotic lesions. To
      examine this, we cloned the rabbit TIMP-1 gene from aortic neointima, developed
      in response to a balloon-catheter induced de-endothelialization. The apparent
      homology of cDNA with TIMP-1 genes from several sources suggested that it is a
      rabbit form of TIMP-1. We examined the recombinant rabbit TIMP-1 expression in
      Escherichia coli using the pTrxFus expression system and the synthesis of the
      resulting soluble protein was confirmed by immunostaining with anti-TIMP-1. The
      TIMP-1 concentration in normal and de-endothelialized rabbit aortas was compared
      using Northern blot, Western blot and mRNA in situ hybridization techniques. We
      observed a significant increase of TIMP-1 expression in neointimal SMCs at both
      nucleic acid and protein levels, suggesting a role of TIMP-1 in injury-induced
      atherogenesis.

PMID- 8879439
TI  - Effects of gemfibrozil on very-low-density lipoprotein composition and low
      density lipoprotein size in patients with hypertriglyceridemia or combined
      hyperlipidemia.
AB  - To examine the effects of gemfibrozil on very-low-density lipoprotein (VLDL)
      composition and low-density lipoprotein (LDL) size, five men with
      hypertriglyceridemia (HTG) alone and five men with HTG and hypercholesterolemia
      (combined hyperlipidemia, CHLP) were randomized for 8 weeks to Lopid SR (slow
      release gemfibrozil; two 600-mg tablets once per day) or placebo in a crossover
      study. Drug therapy versus placebo significantly decreased plasma triglyceride
      (68%), and VLDL (77%), and significantly increased high-density lipoprotein
      cholesterol (25%); total cholesterol, apolipoprotein B and lipoprotein[a]
      concentrations did not change significantly. With drug, mean total apoE in plasma
      was 53% lower in patients with HTG and 39% lower in patients with CHLP.
      Gemfibrozil significantly affected VLDL composition: protein increased 26%, molar
      ratio of apoE to apoB reduced 48%, apoC-II increased 19%, and apoC-III decreased
      9%. LDL cholesteryl ester significantly increased with drug treatment. VLDL
      subfractions were separated and classified as heparin binding (VLDLR, apoE rich)
      or nonbinding (VLDLNR-1 and VLDLNR-2, both apoE poor). All VLDL subfractions were
      significantly lower with drug therapy, and the differences for total VLDL and for
      VLDL subfractions were greater in patients with HTG. With placebo, VLDLR
      accounted for 41.8% of VLDL in HTG and 49.0% of VLDL in CHLP, reduced to 27.6%
      and 38.6%, respectively, with gemfibrozil. Taken together, these results suggest
      that treatment with gemfibrozil reduces plasma concentrations of VLDL and alters
      the apoprotein composition of VLDL in a manner that may favor LDL- and VLDL
      receptor-mediated clearance of the apoE-rich VLDL subfraction, thereby reducing
      TG-rich particle concentrations, and possibly reducing risk for coronary heart
      disease.

PMID- 8879440
TI  - Seasonal variation in parameters related to coronary heart disease risk in young
      men.
AB  - Seasonal variation in the plasma lipids and lipoproteins is reported in the
      literature. Whether this variation is the result of changes in diet or other
      factors has not been adequately addressed. We investigated the effects of a
      controlled diet on the seasonal variation in the levels of plasma lipids and
      apolipoproteins and also on the excretion of urine metabolites of TXA2 and PGI2
      in healthy males. Two well-controlled diet studies were conducted to evaluate
      effects of dietary fatty acids on plasma lipids (Studies 1 and 2; n = 33) and
      eicosanoid excretion (Study 2 only; n = 15). Participants consumed whole-food
      test diets in a randomized, four-period crossover design during each 26-day
      experimental period. A non-intervention control group also participated in each
      study (Study 1, n = 12; Study 2, n = 11). Blood was collected monthly and
      analyzed for plasma lipids and apolipoproteins A-1 (Apo A-1) and B100 (Apo B).
      Twenty-four hour urine samples were collected monthly only in Study 2 and
      analyzed for TXB2 and 6-keto-PGF1 alpha by RIA. Seasonal fluctuations were
      observed in all subjects in plasma Apo A-1 (zenith = July, with 95% CI June-July;
      P < 0.05) and Apo B (zenith = October, 95% CI September-November, P < 0.05).
      Although there was no significant variation in plasma cholesterol levels, the
      increase in Apo B is consistent with an increase in LDL particle number during
      the fall/winter. Additionally, excretion of both eicosanoid metabolites and the
      ratio of 6-keto-PGF1 alpha/TXB2 was markedly elevated in July (95% CI June-July,
      P < 0.001). Three seasonal fluctuations were observed both in participants who
      consumed a highly-controlled experimental diet and in the non-intervention
      controls. Thus, these results suggest a diet-independent seasonal variation in
      parameters thought to be involved in coronary heart disease risk status. An
      understanding of these variations is important not oly for clinical evaluation
      and metabolic study design issues, but more importantly, to clarify their
      clinical significance with the seasonal incidence of CHD events.

PMID- 8879441
TI  - Preparation and biodistribution of 99m technetium labelled oxidized LDL in man.
AB  - Radiolabelled autologous low density lipoprotein (LDL) has previously been used
      to study in vivo distribution and metabolism of native-LDL. Non-invasive imaging
      of atherosclerotic lesions using 99mTc-LDL was shown to be feasible in animal
      models and patients but the clinical utility remains to be assessed. Since recent
      reports suggest that oxidized LDL may play a major role in the pathogenesis of
      atherosclerosis, we developed a technique to oxidize autologous LDL and compared
      the biodistribution of oxidized-LDL with that of native-LDL in man. In addition,
      we evaluated the uptake in vivo of oxidized- and native-LDL by atherosclerotic
      plaques. LDL, obtained from human plasma was treated with various combinations of
      copper ions and H2O2 to induce oxidative modification by increasing the content
      of lipid peroxidation products and electrophoretic mobility. When LDL (0.3 mg/ml)
      was incubated with 100 microM Cu2+ and 500 microM H2O2 oxidation occurred rapidly
      within 1 h, and was labelled with 99mTc efficiently as native LDL. In vivo
      distribution studies revealed a faster plasma clearance of oxidized-LDL compared
      to native-LDL, and a higher uptake by the reticuloendothelial system. Tomographic
      scintigraphy of the neck in patients suffering from transient ischemic attacks,
      revealed accumulation of radiolabelled LDL preparations in the carotid artery
      affected by atherosclerotic lesions. We developed a technique to rapidly oxidize
      LDL using copper and H2O2. Biodistribution data demonstrate that oxidized-LDL is
      rapidly cleared from circulation, is taken up mostly by organs rich in
      macrophages, and can be detected at the level of carotid plaques.

PMID- 8879442
TI  - Dehydroepiandrosterone markedly inhibits the accumulation of cholesteryl ester in
      mouse macrophage J774-1 cells.
AB  - To clarify the antiatherogenic mechanism of action of dehydroepiandrosterone
      (DHEA), we investigated the effects of DHEA on the accumulation of cholesteryl
      ester (CE) in cultured mouse macrophage J774-1 cells. The accumulation of CE in
      J774-1 cells in the presence of acetyl low density lipoprotein (AcLDL) and 10(-5)
      mol/l DHEA was significantly reduced to 30% of the control values for 24 h. The
      marked effect of DHEA was observed as early as 6 h and continued at least for 48
      h. This reduction by DHEA was dose-dependent and occurred starting at a DHEA dose
      of 5 x 10(-7) mol/1 for 24 h. DHEA treatment did not induced any changes in the
      cell surface binding, cell-association, or degradation of AcLDL. In comparison,
      the DHEA analogues, 8354 and 8356, which are known to be much stronger inhibitors
      of glucose 6-phosphate dehydrogenase than DHEA, did not show as marked an effect
      as DHEA on the accumulation of CE during the first 6 h. However, after 24-48 h of
      incubation, both 8354 and 8356 caused a marked reduction in the accumulation of
      CE similar to that observed with DHEA. A quantitative analysis of the cellular
      cholesterol content revealed that DHEA caused a marked reduction in CE with a
      concomitant continuous increase in free cholesterol (FC), while the DHEA
      analogues caused a marked reduction in CE with no change in FC. DHEA demonstrated
      little inhibitory effect on 25-hydroxycholesterol-driven esterification.
      Moreover, 10(-5) mol/1 DHEA induced a CE reduction in the foam cells induced by
      AcLDL. The CE-reducing capacity was also observed in the DHEA analogues. This CE
      reducing capacity disappeared, however, when acyl CoA:cholesterol acyltransferase
      inhibitor, 58-035, was also present. Based on these findings, it can be concluded
      that the inhibitory effect of DHEA on the CE storage in response to AcLDL can be
      explained, at least in part, by two mechanisms. First, a recently published
      mechanism, namely, the inhibitory action of DHEA on lysosomal cholesterol
      transport, correlates well with the inhibition against foam cell transformation
      by DHEA in the early phase (at 6 h) observed in our study. With regard to the
      second mechanism, the CE-reducing capacity of DHEA from CE-laden foam cells,
      which appears to be related to a decreased cholesteryl ester cycle, may
      contribute to the inhibitory effect on the CE storage in the late phase (at 24 h
      and 48 h). These phase-specific inhibitory mechanisms of DHEA on the CE-storage
      may therefore partly explain the antiatherogenic action of DHEA.

PMID- 8879443
TI  - Trans unsaturated fatty acids in plasma phospholipids and coronary heart disease:
      a case-control study.
AB  - A high intake of trans fatty acids (TFAs) has been shown to have an undesirable
      effect on serum lipid profiles and lipoprotein(a) (Lpa)) levels and may thereby
      increase the risk for coronary heart disease (CHD). We performed a study in CHD
      patients, and measured the TFA concentration of the plasma phospholipid fraction.
      Comparison was made between a case group with angiographically documented severe
      CHD (> 80% stenosis in one coronary vessel, n = 83) and a control group of
      patients who had just minor stenosis on the coronary angiography (< 50% stenosis
      in all three major vessels, n = 78): All subjects were under 68 years of age and
      were prestratified on age, gender and smoking habits. The two groups were
      comparable according to the prestratification criteria, body mass index, blood
      pressure, number of cigarettes smoked and total fat intake. Controls had higher
      plasma HDL levels (P < 0.001) and lower, albeit not significantly lower, (P =
      0.07) plasma LDL levels. No significant correlations were found between
      percentages of TFAs in plasma phospholipids and plasma LDL or HDL cholesterol
      levels. Of the major fatty acid classes, only the percentage of saturated fatty
      acids was significantly higher in cases (46.2 +/- 0.92%) than in controls (45.8
      +/- 1.07% (means +/- S.D.)). The difference in total TFA content between cases
      and controls (0.32 +/- 0.02% versus 0.35 +/- 0.02%) was -0.03% (P = 0.2). For the
      specific TFAs C16:1n-7tr, C18:1n-9tr and C18: 2n-6tr, just minor differences were
      found. Adjusted odds ratios for tertiles of TFA percentages were 0.56 (0.25-1.23)
      and 0.76 (0.36-1.61) for the highest middle tertile compared to the lowest. These
      findings do not support an association between TFA intake and risk for coronary
      heart disease.

PMID- 8879445
TI  - Click-rate induced facilitation of the acoustic reflex using constant number of
      pulses.
AB  - This investigation was designed to evaluate acoustic reflex thresholds at various
      repetition rates using a constant number of clicks (constant acoustic energy).
      Ipsilateral acoustic reflex thresholds were obtained from 19 left ears by
      presenting 300 clicks at the repetition rates of 50, 100, 150, 200 and 300/s. The
      results showed an improvement in the acoustic reflex thresholds with an increase
      in the repetition rates (rate integration). Thus for the test conditions used in
      the study, rate-induced facilitation of the acoustic reflex thresholds can be
      demonstrated even if the acoustic energy in the stimuli at various rates is held
      constant. Greater acoustic energy at higher repetition rates is unnecessary for
      such facilitation.

PMID- 8879444
TI  - Heterozygous familial hypercholesterolemia in children: low-density lipoprotein
      receptor mutational analysis and variation in the expression of plasma
      lipoprotein-lipid concentrations.
AB  - The phenotypic expression of heterozygous familial hypercholesterolemia (FH) is
      variable form biochemical and clinical standpoints and several genetic and
      environmental factors could contribute to explain this variability. We have
      compared, in a cohort of 266 heterozygous FH children and adolescents (1-19
      years), the variation in plasma lipoprotein-lipid levels among patients defined
      by three mutations in the low density lipoprotein receptor (LDLR) gene.
      Comparison of the plasma total and LDL-cholesterol (LDL-C) levels among the three
      mutation groups revealed significant differences. Plasma total and LDL-C levels
      were significantly higher (P < 0.05) in the group bearing the French-Canadian
      delta > 15 kb null allele mutation (8.17 +/- 1.45 and 6.58 +/- 1.42 mmol/l) and
      in the group with the defective allele C646Y missense mutation (8.18 +/- 1.53 and
      6.65 +/- 1.50 mmo/l) compared to the group with the defective allele W66G
      missense mutation (7.19 +/- 1.23 and 5.62 +/- 1.16 mmol/l). Comparisons of other
      lipoprotein-lipid parameters between FH heterozygotes and normolipemic (n = 120)
      children indicated that all mutation groups had significantly (P = 0.0001) lower
      plasma HDL-cholesterol (HDL-C) levels and a higher total cholesterol (TC) to HDL
      C ratio (P < 0.05). Among FH heterozygote groups, the W66G group had the lowest
      TC to HDL-C ratio. Multivariate analyses revealed that in FH heterozygotes as
      well as in controls, HDL-C levels contributed to a greater proportion of the
      variation in TC to HDL-C ratio than TC. In order to examine the age effect,
      control and FH heterozygote delta > 15 kb groups were then subdivided into four
      groups (1-4; 5-8; 9-13, and 14-19 years). The variation in HDL-C and
      triglycerides with age in heterozygous FH children showed a pattern which was
      similar to the one noted in the control group. In conclusion, the present study
      demonstrated that the overall contribution of age to variation in the lipoprotein
      profile of heterozygous FH children is similar to the effect observed among
      healthy children. The effect of LDLR gene in FH is dominant and there was no
      difference in plasma TC and LDL-C due to gender. Finally, this study indicates
      that the LDLR gene type mutations are a modulator of the magnitude of the
      increase in plasma TC and LDL-C levels noted among FH heterozygote children.

PMID- 8879446
TI  - The effects on transient evoked otoacoustic emissions following changes in
      external auditory canal acoustic impedance.
AB  - The form of the transient evoked otoacoustic emission (TEOAE) generated by an
      acoustic impulse and recorded in the external auditory canal is dependent on many
      factors. Of these, the acoustic impedance of the external canal is possibly the
      most important. The effect of a change of acoustic impedance on the TEOAEs,
      induced by filling the external canal with helium or sulphur hexafluoride gas, is
      measured in a group of normal hearing subjects. The fundamental frequency of the
      TEOAEs is found to depend upon the density of the gas in the external canal.
      Compared to that of air (density 1.29 g/l) the frequency increased with helium
      (density 0.178 g/l) and decreased with sulphur hexafluoride (density 6.6 g/l).
      The amplitude of the TEOAEs was also found to depend upon the density of the gas
      in the canal, decreasing with helium and increasing with sulphur hexafluoride.
      These results suggest that the TEOAEs observed in the group of subjects tested
      arose within the external auditory canal. This does not imply that cochlear
      emissions are not generated in response to transient acoustic impulses, rather it
      implies that this study failed to show the presence of a cochlear-mediated
      emission.

PMID- 8879447
TI  - Frequency-specific auditory brainstem responses in adults with sensorineural
      hearing loss.
AB  - The purpose of this study was to investigate the prediction of pure tone
      thresholds from auditory brainstem response (ABR) thresholds to tone bursts in
      noise using two formulae: (1) a correction factor based on the average difference
      between pure tone thresholds and ABR thresholds, and (2) a regression equation
      describing the relationship between pure tone thresholds and ABR thresholds.
      Twenty subjects with mild to moderate sensorineural hearing loss were tested with
      tone bursts having 1 millisecond rise-plateau-fall times in highpass noise (500
      Hz) and notch noise (1000, 2000, and 4000 Hz). The data revealed that the pure
      tone-ABR threshold difference systematically decreased as frequency increased.
      Mean differences were approximately 25 dB at 500 Hz and 1000 Hz, 15 dB at 2000
      Hz, and 10 dB at 4000 Hz. Using these correction factors, approximately 90 per
      cent of pure tone thresholds were predicted within +/- 10 dB at 2000 Hz and 4000
      Hz, and within +/- 20 dB at 500 Hz and 1000 Hz. Similar results were found using
      the regression formulae. The results suggest that ABR thresholds to tone bursts
      in noise may provide valuable information on the auditory sensitivity and
      audiometric configuration of difficult-to-test patients.

PMID- 8879448
TI  - Characterization of the brainstem auditory evoked potential (BAEP) in the grey
      short-tailed opossum (Monodelphis domestica).
AB  - Brainstem auditory evoked potentials (BAEP) have been measured and characterized
      in the marsupial Monodelphis domestica in response to toneburst stimulation. Five
      peaks are usually identified. The BAEP occurs within a time window of 5 ms
      starting 1.2 ms after onset of stimulation. Latencies decrease with increasing
      stimulus level at a rate of about -11 microsecond/dB. At high stimulus
      frequencies latencies are shorter than with lower frequencies and shorten at a
      rate of about -0.2 ms/octave. The wave pattern changes in dependence on stimulus
      frequency and stimulus level. An additional peak between peaks ii and iii occurs
      for frequencies above 12 kHz at stimulus levels well above threshold.

PMID- 8879449
TI  - Bilaterally preserved otoacoustic emissions in four children with profound
      idiopathic unilateral sensorineural hearing loss.
AB  - Severe to profound unilateral sensorineural hearing loss of the left ear was
      discovered by screening in four healthy children without any family history of
      hearing loss. Three of the children were four years old and one child was seven
      years old at the time of discovery. The PTA0.5-2 was 66-75 dB HL for three of the
      children and one child was without any hearing reactions on the affected ear. The
      hearing of the right ear was normal in all four cases. The hearing thresholds
      have been stable during an observation period of 3-12 years. No certain auditory
      evoked brainstem responses were recorded with stimulation of the affected ear.
      Electronystagmography was normal in all cases and magnetic resonance imaging gave
      no explanation of the hearing loss. Repeated recordings of the transiently evoked
      otoacoustic emissions (TEOAE) have shown clear bilateral responses using
      different instrumentation systems. Recently the hearing levels were unchanged and
      the TEOAE responses of the affected ears were 6.7-19.9 dB SPL (waveform
      reproducibility: 88-98 per cent) recorded on the ILO88 OAE Analyser (stimulus:
      82.2-83.4 dB peak). The collected results suggest that the children suffer from a
      similar disorder with a unilateral affection of the cochlea, involving the inner
      hair cells and/or the first neuron. The TEOAE recordings indicate substantially
      preserved outer hair cell function independent of the profound hearing loss.

PMID- 8879450
TI  - Majority of thyroid peroxidase autoantibodies in patients with autoimmune thyroid
      disease are directed to a single TPO domain.
AB  - Murine monoclonal antibodies (mAb) produced against native human thyroid
      peroxidase (TPO) are powerful tools for analyzing the autoantibody (Aab) epitopes
      on TPO. Binding sites of thirteen mAbs cover all or most antigenic regions on
      TPO. We determined the competition between Aabs from 75 AITD patients and 13 mAbs
      in binding to TPO. Autoantibodies recognize predominantly the TPO area close or
      identical to mAb#9 epitope. All sera tested inhibited this mAb binding by 92.9 +/
      14.8 (mean +/- SD), range from 69-100%. AITD patients' sera with low Aabs titer
      up to 1/2,000 inhibited mAb#9 binding to TP0 by 85 +/- 11.5% (mean +/- SD) and
      did not influence remaining mAbs binding to TPO. With elevated Aab levels the
      inhibition of other mAbs binding was higher, but never exceeded 35%. The amount
      of Aabs yielding 50% inhibition of mAbs binding was lowest for mAb#9. In order to
      obtain this degree of inhibition for other mAbs 5 to 25 times more Aabs were
      needed. Our results demonstrate that the majority of autoantibodies in sera of
      patients with AITD recognize a single immunodominant region on the TPO mapped by
      mAb#9. They account for about 80-90% of serum TPO autoantibodies. The autoimmune
      response to other regions on TPO molecule is directed to several other epitopes,
      but represents quantitatively a minority of autoantibodies. This response
      intensifies with increasing Aabs level in the serum.

PMID- 8879451
TI  - Plasminogen activation in bullous pemphigoid immunohistology reveals urokinase
      type plasminogen activator, its receptor and plasminogen activator inhibitor type
      2 in lesional epidermis.
AB  - Keratinocytes synthesize urokinase-type plasminogen activator (uPA) and a
      specific cell surface receptor for uPA (uPA-R, CD 87). Plasminogen is present in
      plasma and interstitial fluids from where it is bound to cell surfaces via
      plasmin(ogen) binding sites. uPA binds to the uPA-R in an autocrine manner and
      activates cell-bound plasminogen: a mechanism, which provides plasmin for
      pericellular proteolysis. Cell-bound uPA is regulated by plasminogen activator
      inhibitor type-1 (PAI-1) or type-2 (PAI-2). Bullous pemphigoid is an autoimmune
      inflammatory skin disease characterized by subepidermal blisters. Although
      circumstantial evidence suggested plasminogen activation in lesional epidermis of
      bullous pemphigoid, immunohistological data on the type of plasminogen
      activators, on the uPA-receptor or the type of plasminogen activator inhibitors
      in the lesions of bullous pemphigoid are lacking so far. To obtain this
      information we have performed the present immunohistological study. The presence
      of uPA and its receptor as well as PAI-2 was disclosed in epidermal keratinocytes
      in the roof of the subepidermal blisters. Moreover, keratinocytes at the bottom
      of the blister, which most likely represent keratinocytes during
      reepithelialization were stained. Co-localization was found for uPA and its
      receptor, uPA and plasmin(ogen) as well as for uPA and PAI-2. In non-lesional
      epidermis of bullous pemphigoid only PAI-2 was found. We propose that the
      expression of uPA and uPA-R, as well as the upregulation of PAI-2 in
      keratinocytes of lesional epidermis is part of the repair and reepithelialization
      process following lesion formation, i.e. epidermo-dermal dyshesion, in bullous
      pemphigoid.

PMID- 8879452
TI  - Relation between antibodies to islet cell antigens, other autoantigens and cow's
      milk proteins in diabetic children and unaffected siblings at the clinical
      manifestation of IDDM. The Childhood Diabetes in Finland Study Group.
AB  - The relation between islet cell specific antibodies, other autoantibodies and
      antibodies to cow's milk proteins was studied in IDDM and pre-IDDM by analysing
      islet cell antibodies (ICA), insulin autoantibodies (IAA), anti-nuclear (ANA),
      anti-reticulin class IgA [ARA(IgA)], smooth muscle, anti-mitochondria, parietal
      cell (PCA), adrenal and thyroid antibodies and antibodies to cow's milk formula
      (CMF), beta-lactoglobulin (BLG) and bovine serum albumin (BSA) in a population
      based study with more than 650 children with newly diagnosed IDDM and more than
      550 initially non-diabetic siblings. After adjustment for age a weak association
      was seen in the diabetic children between IAA and ANA but none between ICA and
      autoantibodies directed against the other organ-specific or non-organ-specific
      antigens. There was no significant difference in cow's milk antibodies between
      diabetic children with and without ICA or IAA. The siblings with ICA had higher
      CMF (IgA and IgM) antibody levels and BLG (IgA) antibody levels than the
      remaining siblings, but no such differences were found when comparing IAA
      positive and negative siblings. Siblings positive for ICA had PCA more often than
      did the ICA-negative siblings, whereas siblings positive for both ICA and PCA had
      increased levels of antibodies against CMF, BLG and BSA. These findings indicate
      that the humoral islet cell-associated autoimmunity characteristic of recent
      onset childhood IDDM is clearly restricted to the islet cells and not directly
      related to signs of other organ-specific or non-organ-specific autoimmunity. The
      observation of increased levels of antibodies to cow's milk proteins in siblings
      positive for ICA suggests that the immune response to cow's milk proteins may be
      related to the progressive autoimmune process resulting in beta-cell destruction
      and ultimately in the clinical manifestation of IDDM. Gastrointestinal autoimmune
      mechanisms may play a role in the pathogenesis of IDDM, and the association
      observed between combined ICA and PCA positivity and increased levels of
      antibodies to cow's milk proteins in the siblings implies that there may be an
      enhanced transfer of nutritional antigens across the gut barrier in these
      subjects.

PMID- 8879453
TI  - Mouse thyroglobulin: conservation of sequence homology in C-terminal immunogenic
      regions of thyroglobulin.
AB  - cDNA encoding 287 amino acids of the C-terminus of mouse thyroglobulin was cloned
      and sequenced. The amino acid homology between mouse and rat thyroglobulin was
      96%, and was 78% between mouse and human. It was found that mouse thyroglobulin
      completely shared homology with two thyroiditogenic peptides described by other
      investigators. These findings are consistent with our hypothesis that in murine
      experimental thyroiditis, the primary thyroiditogenic epitopes are encoded by
      mouse-specific regions of thyroglobulin.

PMID- 8879454
TI  - Intracellular ionic changes induced by bullous pemphigoid IgG subclasses.
AB  - To ascertain whether membrane signal transduction is induced by bullous
      pemphigoid (BP) antibody and whether cell lysis is induced by its complement
      activation, we assessed the intracellular Ca2+ concentration ([Ca2+]i),
      intracellular pH, membrane potential and morphology of living cells by following
      the time course of fluorescence intensity of Fluo-3/AM, Snaff-1/AM, Dioc-5 and
      Luciffer yellow, respectively. A transient increase of Fluo-3 fluorescence
      intensity in DJM-1 cells (a squamous cell carcinoma line) was revealed when the
      cells were incubated with 2 of five IgG1 BP antibodies. However, no transient
      increase of Fluo-3 fluorescence intensity was revealed when the cells were
      incubated with IgG2 and IgG4 BP antibodies. A transient increase of Fluo-3
      fluorescence intensity was revealed in DJM-1 cells incubated with 3 of seven IgG1
      and 1 of four IgG2 BP antibodies in an EGTA-containing low-Ca2+ medium. On the
      other hand, the Dioc-5 fluorescence intensity did not change significantly,
      though the increase of Fluo-3 fluorescence intensity was observed. The increase
      of Snarf-1 fluorescence intensity was revealed in DJM-1 cells incubated with 2 of
      five IgG1 BP antibodies, but was not revealed in the cells incubated with IgG2 or
      IgG4 of BP antibodies. Study of complement activation by BP IgG1 showed a
      transient increase of Fluo-3 fluorescence intensity of with 3 of five IgG1 BP
      antibodies when DJM-1 cells were incubated with complement-supplemented normal
      Ca2+ medium. At the same time, however, endocytosis and cell lysis were not
      observed with 2 IgG1 BP antibodies which did induce an increase of Fluo-3
      fluorescence intensity when Lucifer-yellow-loaded DJM-1 cells were incubated with
      complement-supplemented normal-Ca2+ medium. We examined next whether anti-180 kD
      BP antigen monoclonal antibodies (mAbs R-223 and 233) induce an increase of Fluo
      3 fluorescence intensity. MAb R-223 did not induce any increase of Fluo-3
      fluorescence intensity in DJM-1 cells, when incubated with normal- and low-Ca2+
      media However, mAb R-223 induced a transient increase of Fluo-3 fluorescence
      intensity in DJM-1 cells when incubated with complement-supplemented normal-Ca2+
      medium. MAb 233 did not induced an increase of Fluo-3 fluorescence intensity in
      DJM-1 cells when incubated with normal- and low-Ca2+ media. These results suggest
      that the BP IgG1 induces Ca2+ release from intracellular storage sites, however,
      the complement activated by BP IgG1 does not induce cell lysis. It could not be
      confirmed that anti-180 kD BP antigen antibody induced Ca2+ release from
      intracellular storage sites.

PMID- 8879455
TI  - A greater variability in the 3' flanking region of the IL-6 gene in patients with
      systemic lupus erythematosus (SLE).
AB  - The causes of the aberrant constitutive expression of cytokines in SLE have not
      been elucidated yet, but alterations in cytokine gene structure could be a
      contributing factor. By RFLP (Restriction Fragment Length Polymorphism) analysis
      of genomic DNA, we found a higher incidence of allelic, higher MW XbaI bands in
      the IL-6 genes of 9/57 SLE patients vs 1/36 unrelated controls (p = 0.05) HLA
      DR/DQ typing of the polymorphic patients revealed they were all DQ beta 6. The
      study of one family indicated that the XbaI polymorphic patient and her
      polymorphic unaffected offspring had higher than normal levels of constitutive IL
      6 mRNA. The SLE-associated IL-6 XbaI restriction alleles had duplications of AT
      repeat sequences, approximately 500 bp downstream of the 2nd polyadenylation
      site, in an AT-rich mini-satellite with similarities to Matrix Associated Regions
      (MARs), that may be important in DNA replication and in gene expression. These
      are novel observations that suggest that, in SLE, there is increased variability
      in the 3' flanking region of the IL-6 gene. This variability may be related to
      the aberrant IL-6 expression that was reported by us and others in this disease.

PMID- 8879456
TI  - Predicting completeness of symptom relief after major heart surgery.
AB  - The authors hypothesized that the same biopsychosocial factors that raise the
      risk of illness incidence would influence the speed and completeness of relief
      from physical symptoms during recovery following cardiac surgery. This
      multicenter prospective study involved 463 patients aged 35 to 69 years who
      underwent coronary artery bypass graft or cardiac valve surgery. Predictor data
      were gathered 1 to 3 days before surgery, and outcome measures were collected 6
      months postoperatively. The following predictors were associated with
      postoperative freedom from cardiac symptoms: fewer preoperative cardiac
      hospitalizations; low levels of angina, dyspnea, fatigue, and sleep problems; low
      levels of anxiety, depression, hostility, and life-change events; and high levels
      of psychosocial well-being, hopefulness, overall satisfaction, and social
      support. The predictors of not requiring daytime bed rest because of cardiac
      symptoms during the 6th postoperative month were male gender, higher education,
      less cardiac disability preoperatively, low levels of angina, dyspnea, sleep
      problems, depression and fatigue, and absence of Type A behavior and of
      intraoperative hypotension. By using separate multiple logistic regression
      equations, the authors identified the variables printed in bold face as
      independent significant contributors to prediction. Many of the predictors are
      strong enough and simple enough to be used in clinical practice. Many of them may
      also predict recovery after acute illnesses and injuries involving other organ
      systems.

PMID- 8879457
TI  - Higher levels of social support predict greater survival following acute
      myocardial infarction: the Corpus Christi Heart Project.
AB  - Although low levels of social support have been related to mortality from
      coronary heart disease, little is known about the role of social support among
      Mexican Americans. The authors therefore examined the relationship between social
      support and long-term survival in the Corpus Christi Heart Project. They
      developed a social support scale that used data collected during in-hospital
      interviews of 292 Mexican Americans and 304 non-Hispanic Whites who survived a
      myocardial infarction for more than 28 days. The scale incorporated three
      measures: marital status; if not married, whether living alone; and whether
      advised to seek help. During an average follow-up period of 43 months, 115
      participants died. Survival following myocardial infarction was greater for those
      with high or medium social support than for those with low social support. With
      age, gender, ethnicity, education, employment, smoking, diabetes, hypertension,
      and hypercholesterolemia included in a proportional hazards regression model, the
      relative risk of mortality was 1.89 (95% CI, 1.20-2.97) for those with low social
      support. But when the two ethnic groups were analyzed separately, low social
      support was no longer a significant predictor of mortality for non-Hispanic
      Whites, whereas for Mexican Americans, the relative risk of mortality was 3.38
      (95% CI, 1.73-6.62) for those with low social support.

PMID- 8879458
TI  - Components of Type A behavior pattern and occupational stressor-strain
      relationship: testing different models in a sample of industrial managers.
AB  - The authors analyzed empirically the roles of impatience-irritability and
      ambition-energy components of the Type A behavior pattern (TABP) in the
      occupational stressor-strain relationship. They tested three models, using a
      sample of 659 industrial managers to determine whether the TABP components
      affected strain independently from perceived stressors (the direct effects
      model); or indirectly, by moderating effects of perceived stressors (the
      moderated effects model); or whether perceived stressors provoked TABP
      components, which influenced the number of strain symptoms (the mediated effects
      model). Multiple regression procedures showed, as expected, that the two TABP
      components acted quite differently in the stress process. With the direct effects
      model, the impatience-irritability component consistently increased numbers of
      psychological and physiological symptoms, regardless of perceived occupational
      stressors. The ambition-energy component, on the other hand, was activated by an
      abundance of development possibilities experienced at work. This, in turn, partly
      explained the decrease in perceived levels of psychological and physiological
      symptoms. The results relating to the ambition-energy component supported the
      mediated effects model and demonstrated a positive effect on subjective health
      perceptions.

PMID- 8879459
TI  - EEG biofeedback as a treatment for chronic fatigue syndrome: a controlled case
      report.
AB  - EEG neurofeedback has been identified as a potential diagnostic and treatment
      protocol with chronic fatigue syndrome (CFS) symptoms. In the present case study,
      the authors applied an EEG neurofeedback biofeedback paradigm as a treatment
      modality with a CFS patient. Baseline data were acquired using the Wechsler Adult
      Intelligence Scale-Revised and qualitative and subjective ratings of cognitive
      improvement. Test results and clinical findings revealed improvements in the
      patient's cognitive abilities, functional skill level, and quality of life. The
      patient showed significant differences in pre- and posttest levels on the
      Wechsler scale.

PMID- 8879460
TI  - Increases in depression after cholesterol-lowering drug treatment.
AB  - To investigate the possibility that increases in depressive symptoms might occur
      in patients who have undergone cholesterol-lowering interventions, the authors
      administered the Center for Epidemiological Studies-Depression scale before and
      after cholesterol lowering to 6 men who were referred to a lipid clinic. All of
      the patients' cholesterol levels were reduced after the 6-week intervention, and
      4 of the patients' depression scores increased; scores of 2 of the 4 met the
      criteria for mild clinical depression. Further study of possible links among low
      cholesterol, depressive symptoms, and serotonergic activity is needed.

PMID- 8879461
TI  - Depression and cholesterol-lowering chemotherapy: potential influence of smoking
      cessation, depression history, and dietary change.

PMID- 8879462
TI  - Plasma protein variations in monozygotic twins discordant for schizophrenia.
AB  - Monozygotic twins discordant for schizophrenia were analyzed by two-dimensional
      (2-D) gel electrophoresis to identify extrahereditary factors important in the
      development of schizophrenia. Plasma protein patterns in 2-D gels of monozygotic
      twins discordant for schizophrenia were found to be significantly less alike than
      those of normal control monozygotic twins. Several polypeptide spots were found
      to be elevated in the plasma of the schizophrenic twin. One of these
      polypeptides, spot 782, was also found to be significantly (p < .001) elevated
      when schizophrenic patients were compared to unrelated normal control
      individuals. Spot 782 may be an isoform of haptoglobin. Quantitative variations
      in some plasma haptoglobin levels were seen between discordant twins, but not
      between unrelated schizophrenic and normal control individuals.

PMID- 8879463
TI  - Relationships between verbal memory performance and the cerebral distribution of
      fluorodeoxyglucose in patients with schizophrenia.
AB  - Quantitative resting fluorodeoxyglucose-positron emission tomography scans were
      performed on 42 patients with schizophrenia. Magnetic resonance imaging-based
      regions of interest were transposed onto the corresponding positron emission
      tomography images. Region to whole brain ratios were calculated from the mean
      regional activity per pixel across both hemispheres (left plus right). Laterality
      scores were calculated from the difference between the mean activity in homotopic
      regions of the two hemispheres (left minus right). Subjects were tested
      contemporaneously with the Logical Memory subtest of the Wechsler Memory Scale.
      The subtest was scored with modified criteria to provide information about verbal
      recall, perseverations, and other components of verbal memory. Deficits in recall
      were associated with increased metabolism in selected regions of the left
      hemisphere that are known to mediate aspects of verbal memory. The findings
      support hypotheses suggesting that the left hemisphere is functionally overactive
      in schizophrenia.

PMID- 8879464
TI  - Electroencephalography in schizophrenic patients: comparison between neuroleptic
      naive state and after treatment.
AB  - Electroencephalography of 12 schizophrenic patients was recorded in a neuroleptic
      naive state and after 6.2 +/- 1.1 months of treatment, when they were on
      medication and in partial remission. Compared with age- and sex-matched controls,
      the neuroleptic-naive schizophrenics had less alpha 2 power. In the medicated
      state, alpha 2 power and slow-wave power were reduced as compared with the
      neuroleptic-naive state. The reduction in alpha 2 power may occur from the early
      stage of the disease and progress even though the patients are medicated and
      clinically improved.

PMID- 8879465
TI  - X chromosome and infantile autism.
AB  - Family studies and epidemiologic data in autism show the involvement of genetic
      factors in the etiology of this syndrome. The frequent association of X
      chromosome with mental retardation and behavior disturbances raises the question
      of its implication in the etiology of autism. Several markers of X chromosome
      were tested in autistic and control populations by association study. The
      autistic population was submitted to an extensive clinical examination. For the
      DXS287 marker, chi 2 analysis showed a different allele distribution between
      control and patient groups. This difference was enhanced when children with the
      most severe autistic behaviors and the least serious cognitive disorders were
      selected for statistical comparison. To our knowledge, this is the first
      association study described using markers of X chromosome in infantile autism.
      These preliminary results encourage our research on this chromosome, which could
      be considered as a significant genetic component of the multifactorial etiology
      of autism.

PMID- 8879466
TI  - Initial increase of plasma serotonin: a biological predictor for the
      antidepressant response to clomipramine?
AB  - Hypofunction of the serotonin (5-HT) system might be involved in depression.
      Initial effects of the 5-HT reuptake inhibitor clomipramine (CMI) on plasma 5-HT
      have never been assessed. On Day 1, 27 depressed patients received either a 25-mg
      CMI slow infusion or a 25-mg CMI tablet in a randomized, double-blind, double
      dummy design. The daily dose was subsequently titrated up to 75 mg i.v. or 150 mg
      orally. The Montgomery-Asberg Depression Rating Scale (MADRS) was rated on Days
      1, 4, 7 and 14. High-performance liquid chromatography (HPLC-EC) assays of plasma
      5-HT, platelet 5-HT, and CMI were performed on Day 1 before and after the
      infusion. On Day 1, both groups experienced a mean (nonsignificant) plasma 5-HT
      increase; in the i.v. group this initial increase correlated with MADRS decrease
      over 14 days (r = 0.76, p = .0025). Correlations between platelet 5-HT and MADRS
      decrease were not significant. These preliminary data show that: i) CMI
      administration results in initial changes in plasma 5-HT; and ii) i.v. CMI
      induced initial plasma 5-HT increase is consistent with the CMI 5-HT profile, and
      might predict the clinical response to CMI.

PMID- 8879467
TI  - The relationship between longitudinal clinical course and sleep and cortisol
      changes in adolescent depression.
AB  - This study examined the relationship between longitudinal clinical course and
      sleep and cortisol findings in adolescent unipolar major depressive disorder
      (MDD). Subjects were 28 adolescents (15.4 +/- 1.3 years) systematically diagnosed
      with unipolar MDD and 35 group-matched normal controls who participated in EEG
      sleep and neuroendocrine studies. Follow-up clinical assessments were conducted
      7.0 +/- 0.5 years later in 94% of the original cohort. Although initial group
      comparisons failed to show significant differences in biologic measures, analyses
      incorporating clinical follow-up reveal that changes in sleep and cortisol
      measures are associated with differential longitudinal course. Normal controls
      who would develop depression after the biologic studies had shown significantly
      higher density of rapid eye movements (REM) and a trend for reduced REM latency
      compared to controls with no psychiatric disorder at follow-up. Depressed
      subjects with a recurrent unipolar course showed a trend towards elevated plasma
      cortisol near sleep onset compared to MDD subjects with no further episodes
      during the follow-up interval.

PMID- 8879468
TI  - Sleep electroencephalogram in seasonal affective disorder and in control women:
      effects of midday light treatment and sleep deprivation.
AB  - The role of sleep regulation in Seasonal Affective Disorder (SAD) was studied in
      11 female SAD patients and eight controls in winter before and after light
      treatment (LT, 6000 lux, 10-14h, 5 days). The sleep electroencephalogram (EEG)
      was recorded at baseline and after the total sleep deprivation (TSD) of a 40-h
      constant routine. The well-known effects of TSD on sleep parameters and on EEG
      power spectra were replicated, indicating normal homeostatic sleep regulation in
      SAD. Sleep improved after LT in both groups. Since the condition following LT was
      the second session, these improvements may be an order effect and/or an effect of
      LT itself. After LT, sleep EEG spectra of SAD patients, but not of controls,
      showed modifications resembling those of recovery sleep. Since only SAD patients
      curtailed their sleep while remitting during the LT period, these EEG
      modifications can be explained by normal sleep regulation alone. We conclude that
      the robust antidepressant effect of LT in SAD is unlikely to be mediated by
      changes in sleep, and that sleep regulatory mechanisms are not a crucial factor
      in the pathogenesis of winter depression.

PMID- 8879469
TI  - Antipsychotic drugs block IP3-dependent Ca(2+)-release from rat brain microsomes.
AB  - Cellular Ca(2+)-dysregulation has been proposed as an important mechanism in
      certain diseases such as bipolar affective disorder (BPAD) and malignant
      hyperthermia. Recently it has been found that in BPAD, the plasma membrane Ca(2+)
      channel blockers verapamil and nimodipine are useful substitutes in Li(+)
      treatable patients. We have investigated the effects of these drugs and the
      antipsychotic drugs (clozapine, fluspirilene, and haloperidol) on IP3-induced
      Ca(2+)-release from Ca(2+)-loaded rat brain microsomes. In the presence of either
      the Ca(2+)-channel blockers or the neuroleptic drugs, Ca(2+)-release was blocked
      in a dose-dependent fashion. For the neuroleptics, the EC50 ranged from 22 microM
      for fluspirilene to 145 microM for haloperidol. The EC50 for nimodipine was 160
      microM and 450 microM for verapamil. Carbamazapine and valproic acid,
      anticonvulsants recently used for treating BPAD, were relatively ineffective, as
      were various haloperidol metabolites. The research described in this paper
      establishes for the first time that antipsychotic drugs, as well as certain
      Ca(2+)-channel blockers, directly block the IP3-induced Ca(2+)-release in a rat
      brain microsome assay.

PMID- 8879470
TI  - Induction of tetradecanoyl phorbol acetate-inducible sequence (TIS) genes by
      electroconvulsive shock in rat brain.
AB  - We studied the induction of tetradecanoyl phorbol acetate-inducible sequences
      (TIS)1, 7, 8, 11, and 21 in rat cerebral cortex, hippocampus, and cerebellum
      after electroconvulsive shock (ECS). These genes were reported to be induced by
      depolarization in PC-12 cells. Single ECS induced TIS1, 8, 11, and 21, but not
      TIS7 genes in the rat brain regions examined. In cerebral cortex and hippocampus,
      induction of TIS1, TIS8, and TIS21 reached peak at 30 or 45 min after ECS. The
      induced mRNA of TIS1 and 21 decreased rapidly and returned almost to the basal
      level by 90 min after ECS, whereas those of TIS8 and 11 lasted longer. In
      cerebellum, TIS genes were induced and disappeared more rapidly than in the other
      two regions. The 10 and 20 daily ECSs did not affect the inducibility of TIS1,
      11, and 21 in cerebellum, but the induction of TIS8 was attenuated by 35% after
      20 daily ECSs. Our study indicated that ECS could induce some of the TIS genes in
      various rat brain regions, but the induction patterns were different depending on
      the TIS genes and brain regions. Our study also suggested that chronic ECS could
      not attenuate the induction of some immediate early genes.

PMID- 8879471
TI  - m-Chlorophenylpiperazine challenge in borderline personality disorder:
      relationship of neuroendocrine response, behavioral response, and clinical
      measures.
AB  - We have previously found that a subgroup of patients with impulsive personality
      disorders respond to m-chlorophenylpiperazine (m-CPP) administration with a
      distinctive spacy/high behavioral reaction and with increased cortisol responses.
      In this report we analyzed the relationship between behavioral and neuroendocrine
      responses to m-CPP in an enlarged sample of patients with borderline personality
      disorder (BPD). We also assessed the association of behavioral and neuroendocrine
      responses with clinical symptoms and with m-CPP blood levels. We found that in
      BPD patients the presence of a spacy/high behavioral response was significantly
      associated with increased prolactin and cortisol responses to m-CPP. In BPD
      patients increased m-CPP levels were significantly associated with neuroendocrine
      hypersensitivity and with a spacy/high behavioral response, while in controls
      increased m-CPP levels were not significantly associated with neuroendocrine
      hypersensitivity but were significantly associated with dysphoric behavioral
      responses. Taken together with previous work on m-CPP in obsessive-compulsive
      disorder, these results are partially consistent with the hypothesis that
      compulsive and impulsive symptoms fall at opposite ends of a phenomenologic and
      neurobiologic spectrum.

PMID- 8879472
TI  - Ondansetron alters human alcohol intoxication.
AB  - There is considerable evidence that serotonin-3 (5-HT3) receptor antagonists
      modulate some of the behavioral effects of alcohol, and may decrease alcohol
      consumption. To better clarify the mechanism of action of 5-HT3 antagonists on
      these behaviors, we investigated the effects of the 5-HT3 antagonist,
      ondansetron, on several subjective and objective measures of alcohol intoxication
      in social drinkers. Twelve nonalcoholic, social drinkers received either 8 mg
      ondansetron, p.o., or placebo during one of two test sessions in a crossover,
      double-blind protocol. Both conditions were followed by a standard, intoxicating
      dose of alcohol. Subjective and objective measures of intoxication including
      mood, physical sensations, performance changes, and alcohol pharmacokinetics were
      determined. To control for ondansetron effects, 10 additional subjects received
      either ondansetron or placebo, followed by a nonintoxicating, "placebo" dose of
      alcohol during a second crossover double-blind protocol. Ondansetron was found to
      augment certain stimulant, sedative, and discriminant effects of alcohol, without
      affecting psychomotor performance or alcohol pharmacokinetics. Ondansetron had
      minimal effects on subjects receiving placebo alcohol. These data suggest that
      the reductions in alcohol consumption observed in animals and humans treated with
      ondansetron may be mediated by increases in subjective intoxication, and/or
      increases in the aversive effects of alcohol.

PMID- 8879473
TI  - Event-related brain potentials in children with attention-deficit and
      hyperactivity disorder: effects of stimulus deviancy and task relevance in the
      visual and auditory modality.
AB  - It has frequently been reported that in so-called oddball tasks, children with
      attention-deficit and hyperactivity disorder (ADDH) show small P3 peaks of the
      event-related potential (ERP) in response to "targets" (task-relevant deviant
      stimuli) than normal children. It is not clear, however, whether this smaller P3
      is due to abnormal processing of infrequent stimuli per se and/or of task
      relevant stimuli and whether it is preceded by abnormalities in earlier peaks,
      especially those thought to be related to automatic deviancy detection [mismatch
      negativity (MMN) in the auditory modality and P2N2 in the visual modality]. ERPs
      of ADDH and normal children in response to visual and auditory stimuli were
      studied in a condition without task relevance as well as in a task-relevant
      condition. ADDH children showed smaller P3 amplitudes and (marginally) smaller
      MMN to auditory deviant stimuli, irrespective of task relevance, so smaller P3s
      in ADDH children are due to stimulus deviancy per se. In the visual modality the
      P3 effect failed to reach significance. Because the smaller P3s were also found
      in a condition not requiring task-related motivation, recent motivational
      interpretations of differences with normal children are not supported. ADDH
      children also showed smaller P1 amplitudes than normal children to all stimuli
      except visual novels. The ERP differences were unrelated to performance, since
      both groups performed equally well.

PMID- 8879474
TI  - Cognitive deficits in patients with chronic fatigue syndrome.
AB  - Twenty-nine subjects with chronic fatigue syndrome (CFS) and 25 healthy control
      subjects were administered a lengthy neuropsychological battery that included
      standard neuropsychological tests and a computerized set of tasks that spanned
      the same areas of ability. The primary significant differences between patients
      and controls were found on tests of learning and memory. These differences
      remained when the degree of psychiatric symptomatology in the subjects was
      covaried. Patients on and off psychoactive medications did not differ in their
      performance on these tasks. These results suggest that at least a subset of CFS
      patients may experience significant impairments in learning and memory.

PMID- 8879475
TI  - Serum cholesterol and treatment-resistance in schizophrenia.

PMID- 8879476
TI  - Headache response to m-chlorophenylpiperazine in obsessive-compulsive disorder
      and normal controls.

PMID- 8879477
TI  - Intranasal oxytocin in obsessive-compulsive disorder.

PMID- 8879478
TI  - Effect of CI-988, a cholecystokinin-B receptor antagonist, on lactate-induced
      panic.

PMID- 8879479
TI  - Urinary epinephrine excretion during intelligence testing in attention-deficit
      hyperactivity disorder and normal boys.

PMID- 8879480
TI  - Facial expression in schizophrenia.

PMID- 8879481
TI  - Intranasal oxytocin in trichotillomania.

PMID- 8879482
TI  - Hypothalamic-pituitary-adrenal axis in schizophrenia.

PMID- 8879483
TI  - A unique variant of a homeobox gene related to Drosophila cut is expressed in
      mouse testis.
AB  - Mammalian homologues of the Drosophila cut homeobox gene encode transcriptional
      repressors that are involved in tissue-specific and developmental gene
      regulation. We examined the expression of a murine cut homologue (Cux-1) in the
      adult mouse. In many somatic tissues, Cux-1 was expressed as a 13-kb transcript.
      However, the highest expression of Cux-1 was in the testis, where a unique 2.4-kb
      splice variant was identified. Less abundant transcripts of 5 kb, 6.5 kb, and 8.5
      kb were also detected only in the testis. The nucleotide sequence of the 2.4-kb
      Cux-1 transcript was identical to the 13-kb transcript in the region of overlap,
      but the testis-specific transcript encoded a truncated protein that contained
      only one Cut repeat in addition to the Cut-related homeodomain. Studies of mice
      homozygous for the atrichosis (at/at) mutation suggested that the 2.4-kb
      transcript was expressed in germ cells in the testis. In situ hybridization
      verified that Cux-1 was transiently expressed in post-meiotic germ cells at the
      round spermatid stage. Immunoblot analysis of nuclear extracts showed that the
      testis-specific Cux-1 transcripts encoded a 55-kDa protein. These results
      demonstrate that multiple products of a cut-related homeobox gene are expressed
      in the testis. The highly restricted pattern of expression of Cux-1 in the testis
      suggests that it may be involved in regulation of postmeiotic gene expression.

PMID- 8879484
TI  - Apolipoprotein J/clusterin expression defines distinct stages of blastocyst
      implantation in the mouse uterus.
AB  - The endometrium is a dynamic tissue that responds to hormonal cues and growth
      factors to accommodate, regulate, and nurture developing embryos. To provide
      clues about the molecular mechanisms underlying the responsiveness of this
      tissue, we have begun to identify genes that are expressed at specific stages of
      early pregnancy. One such gene, apolipoprotein J (apoJ), encodes a secretory
      glycoprotein capable of binding lipids and membrane-active proteins. Uterine apoJ
      gene activity was not detected immediately following fertilization, but glandular
      epithelial expression of apoJ mRNA appeared just before the time of blastocyst
      implantation and persisted postimplantation. During implantation, uterine luminal
      epithelial cells also expressed apoJ, but expression was excluded from luminal
      cells adjacent to the sites of attached blastocysts. ApoJ protein accumulated in
      the glandular and uterine lumens in proximity to the epithelial cells that
      expressed apoJ mRNA. We suggest that apoJ expression is a marker of uterine
      receptivity to blastocyst implantation. Subsequent expression of apoJ message in
      uterine stromal cell types and in circular muscle myocytes coincided with the
      onset of decidualization. During this period the myocytes of the longitudinal
      muscle layer showed no evidence of apoJ mRNA. ApoJ protein was localized to
      nondecidualized tissue but was not evident in decidualized cells. In contrast,
      the protein was dispersed throughout both the circular and longitudinal
      myometrium. In the uteri of hormone-treated females stimulated with oil, apoJ was
      also expressed during decidualization in stromal cells and in circular myocytes,
      indicating that signals specifically transmitted from the embryo itself are not
      responsible for apoJ mRNA accumulation.

PMID- 8879485
TI  - Transforming growth factor beta in bovine placentas.
AB  - Transforming growth factor beta s (TGF beta) are a family of multifunctional
      growth factors that are important embryonic morphogens. Because TGF beta s may
      regulate the development of epitheliochorial placentas, we investigated the
      location, expression, secretion, and effects of TGF beta s in bovine placentomes
      and cell cultures derived from chorionic and endometrial epithelia. Placentomes
      from early second-trimester pregnancies were examined by immunohistochemistry for
      TGF beta 1, TGF beta 2, and TGF beta 3, and for TGF beta expression in Northern
      slot-blots. Effects of TGF beta s were assessed in trophoblastic and endometrial
      epithelial cell lines by DNA synthesis assays. Secretion of TGF beta s by
      trophoblastic and endometrial epithelial cells was determined using bioassays.
      All forms of TGF beta were immunolocalized in bovine placentomes. TGF beta mRNA
      was expressed in chorioallantois, caruncles, and in cultured trophoblastic and
      endometrial epithelial cells. Endometrial and trophoblastic cells secreted active
      and latent TGF beta s, and these cells had a transient proliferative response to
      all forms of TGF beta. These results indicate that TGF beta s are present at the
      fetal-maternal interface of the bovine placentome and may promote endometrial and
      chorionic growth.

PMID- 8879486
TI  - Activation of brain-type cannabinoid receptors interferes with preimplantation
      mouse embryo development.
AB  - The recent identification and cloning of guanine nucleotide regulatory protein
      coupled brain-type and spleen-type cannabinoid receptors (CB1-R and CB2-R,
      respectively) provide evidence that many of the effects of cannabinoids are
      mediated via these receptors. Our recent observation of expression of both CB1-R
      and CB2-R genes in the preimplantation mouse embryo suggests that it could also
      be a target for cannabinoids. Indeed, cannabinoid agonists interfered with
      preimplantation embryo development in vitro. To examine whether cannabinoid
      effects on preimplantation embryos are mediated via CB1-R, we developed rabbit
      antipeptide antibodies against the N-terminal region of CB1-R and examined the
      receptor protein in the blastocyst by Western blotting and its spatiotemporal
      distribution in preimplantation mouse embryos by immunohistochemistry.
      Cannabinoid binding sites in the blastocyst were examined by Scatchard analysis,
      while the reversibility of cannabinoid-induced embryonic arrest in vitro was
      monitored using a specific antagonist to CB1-R, SR141716A. Western blot analysis
      detected a major band of approximately 59 kDa and a minor band of approximately
      54 kDa in the blastocyst. Immunocytochemistry detected this receptor protein from
      the 2-cell through the blastocyst stages. Scatchard analysis using 3H-anandamide
      (an endogenous ligand) showed a single class of binding sites in Day 4
      blastocysts with an apparent Kd of 1.0 nM and Bmax of 0.09 fmol/blastocyst.
      Considering the total number of cells (approximately 50) and total protein
      content (approximately 20 ng) of a blastocyst, it is apparent that the mouse
      blastocyst has many more high-affinity receptors than those in the mouse brain
      (Kd: 1.8 nM and Bmax: 18.8 pmol/mg membrane protein). Cannabinoid agonists and
      the CB1-R antagonist SR141716A effectively competed for anandamide binding in the
      blastocyst. To determine whether cannabinoid inhibition of embryonic development
      could be reversed by SR141716A, 2-cell embryos were cultured in the presence of
      cannabinoid agonists with or without SR141716A for 72 h. Most of the 2-cell
      embryos cultured in the absence of the agonists developed into blastocysts
      (approximately 90%). In contrast, the addition of cannabinoid agonists
      anandamide, Win 55212-2, or CP 55,940 in the culture medium severely compromised
      embryonic development: more than 60% of the 2-cell embryos failed to develop to
      blastocysts. A reduction in trophectoderm cell numbers was noted in those
      blastocysts that escaped the developmental arrest in the presence of cannabinoid
      agonists. However, this reduction was corrected when embryos were cultured
      simultaneously with an agonist and SR141716A. Furthermore, embryonic arrest was
      reversed when embryos were cultured simultaneously in the presence of an agonist
      and SR141716A. The addition of SR141716A alone in the culture medium apparently
      had no effects on embryonic development: more than 90% of the embryos developed
      into blastocysts. The results suggest that the CB1 receptors in preimplantation
      mouse embryos are biologically active and cannabinoid effects on them are
      primarily mediated by these receptors.

PMID- 8879487
TI  - Regulation of the estrogen receptor and its messenger ribonucleic acid in the
      ovariectomized sheep myometrium and endometrium: the role of estradiol and
      progesterone.
AB  - Estrogen receptor (ER) mRNA is dramatically increased in sheep myometrium and
      endometrium during glucocorticoid-induced premature labor and term spontaneous
      labor. However, the underlying mechanism for the up-regulation of uterine ER in
      labor is still unknown. We used ovariectomized (OVX) non-pregnant sheep to
      analyze the role of estradiol and progesterone in the regulation of myometrial
      and endometrial ER protein and ER mRNA in vivo. Twenty-one OVX ewes were treated
      with saline (n = 6), or with estradiol infused i.v. for 2 days (50
      micrograms/day, n = 5), or with an intravaginal progesterone sponge for 10 days
      (containing 0.3 g progesterone, n = 5), or with an intravaginal progesterone
      sponge for 10 days with estradiol (50 micrograms/day) administered on Days 9 and
      10 with the progesterone sponge still in place (n = 5). The ER protein
      concentration in both cytosolic and nuclear compartments, analyzed by Western
      blot, increased significantly (P < 0.05) in the myometrium after estradiol
      treatment, while progesterone alone had no detectable effect on ER level.
      Elevated ER protein was observed only in the nuclear fraction of endometrium.
      However, when estradiol was given together with progesterone treatment,
      progesterone antagonized the up-regulatory effect of estradiol on the ER level
      both at the endometrium and myometrium. The changes in cellular ER mRNA followed
      the pattern observed at the ER protein level. Estrogen receptor mRNA was elevated
      significantly (p < 0.01) only in estradiol-treated ewes. Expression of the ER
      gene in ewes receiving progesterone alone or progesterone combined with estradiol
      was similar to that of the control group. From these observations we conclude
      that ER gene expression and active ER synthesis in nonpregnant sheep myometrium
      and endometrium are estradiol-dependent. Progesterone antagonizes this estrogen
      action. Progesterone down-regulated the elevated ER mRNA when used together with
      estradiol. In situ hybridization showed that ER mRNA was evenly distributed in
      the smooth muscle cells and blood vessels of the myometrium and the epithelial
      cells of the glands in endometrium. In conclusion, we have observed estradiol
      dependent activation of ER gene expression as well as active ER synthesis in the
      nonpregnant sheep myometrium and endometrium. Progesterone acted as an antagonist
      of estradiol on ER gene expression.

PMID- 8879488
TI  - Nucleologenesis and ribonucleic acid synthesis in preimplantation equine embryos.
AB  - The nucleolus is believed to be the active site of rRNA synthesis in all
      eukaryotic cells. In preimplantation embryos, the embryonic genome is apparently
      more or less silent up to a species-specific developmental stage at which a major
      burst of transcription occurs. Here we report on nucleologenesis and some
      ultrastructural aspects of the onset of RNA synthesis in equine embryos during in
      vivo development. The zygotes and embryos up to blastocyst stages were surgically
      recovered from normally cycling mares. Mares were induced to ovulate by treatment
      with 3000 IU hCG and inseminated 20 and 34 h later. At different time intervals
      postovulation, mares were anesthetized and ova were collected from oviducts
      removed through a flank incision. The presumptive fertilized ova were incubated
      for 20 min with [3H]uridine and processed for light microscopy, transmission
      electron microscopy (TEM), and TEM autoradiography. Ultrastructurally, electron
      dense nucleolus precursor bodies were observed in zygotes and 2- and 4-cell
      embryos. In 6- and 8-cell embryos, reticulated fibrillo-granular nucleoli
      displaying both fibrillar and granular components were observed. At this stage of
      development, the first autoradiographic labeling was observed over the dense
      fibrillar component of the nucleoli as well as over the nucleoplasm in the 8-cell
      embryos. In the 16-cell embryos and beyond, fully transcriptionally active
      compact fibrillo-granular nucleoli displaying granular and fibrillar components
      as well as fibrillar centers were observed, and autoradiographic labeling was
      detected over the dense fibrillar component of the nucleolus as well as over the
      nucleoplasm. In conclusion, nucleolar activation, including transcription of
      presumptive rRNA and heterogeneous nuclear RNA, is initiated during the fourth
      cell cycle.

PMID- 8879489
TI  - Depletion of insulin in streptozocin-induced-diabetic pigs alters estradiol,
      insulin-like growth factor (IGF)-I and IGF binding proteins in cultured ovarian
      follicles.
AB  - The objectives were to investigate whether insulin-dependent diabetes mellitus
      disrupts production of estradiol and activity of the insulin-like growth factor
      (IGF)-I system in individual ovarian follicles during the preovulatory period of
      the estrous cycle. Diabetes mellitus was induced with streptozocin (150 mg/kg) in
      seven cyclic gilts at 180 +/- 5 days of age. On Day 12 of the estrous cycle,
      insulin replacement therapy was withdrawn from three gilts and continued in four;
      four gilts served as normal controls. After ovary removal on Day 18, all
      follicles > or = 3 mm diameter were dissected free and cultured for 6 h in the
      presence of 280 ng testosterone for assessment of estradiol and IGF-I production
      and binding protein activity. Treatments did not affect corpora lutea number
      (15.4 +/- 0.8) or serum estradiol (5.8 +/- 0.8 pg/ml) on Day 18. There were no
      differences for any measure of follicular development between normal and insulin
      treated diabetic gilts. Untreated diabetic gilts, compared to normal and insulin
      treated diabetic gilts, had fewer total visible follicles (22.7 vs. 61.3 and
      63.3; SEM = 8; p < 0.01) and reduced follicular diameter (3.4 vs. 4.4 and 4.2 mm;
      SEM = 0.3; p < 0.0001), respectively. Untreated diabetic gilts had a greater
      percentage of macroscopically atretic follicles than normal and insulin-treated
      diabetic gilts (75% vs. 47% and 36%; SEM = 10; p < 0.05). Untreated diabetes
      mellitus lowered estradiol (p < 0.01); however, effects of treatment on estradiol
      production were not significant when diameter was part of statistical models.
      When contents of IGF-I in follicular fluid and conditioned medium were summed
      after 6 h of culture, untreated diabetic pigs had lower IGF-I at all follicle
      diameters than pigs in the other treatments (p < 0.05). IGF binding protein (BP)
      activity was affected by diabetes mellitus, with untreated diabetic pigs having
      greater IGFBP-1 activity in medium and with both diabetic groups having greater
      IGFBP-2 activity in follicular fluid (p < 0.05). Activity of IGFBP-1 predominated
      in conditioned medium, and IGFBP-2 activity predominated in follicular fluid.
      IGFBP-3 was decreased in follicular fluid of atretic follicles and in medium of
      atretic follicles in all except the insulin-treated diabetic gilts; in these
      gilts it was increased in atretic follicles (treatment by atresia interaction; p
      < 0.05). In conclusion, estradiol was most related to size of the follicle;
      however, lowering of IGF-I regardless of follicle diameter and alterations in
      IGFBP activity suggest that diabetes affects IGF-I and its binding proteins
      differently from estradiol production. These alterations may explain reduced
      follicular growth and increased follicular atresia in diabetic pigs.

PMID- 8879490
TI  - Estrogen receptor messenger ribonucleic acid changes during Leydig cell
      development.
AB  - Mature (60-65 days old) male Sprague-Dawley rats received a single i.p. injection
      of ethane dimethane sulfonate (EDS, 100 mg/kg BW) and were killed at different
      times from Days 2 to 60 posttreatment. Bands of cells enriched in precursor
      Leydig cells (PLCs) and Leydig cells (LCs) were isolated from the testis of EDS
      treated rats and age-matched controls using a collagenase digestion-Percoll
      gradient method. Total RNA extracted from the PLC and LC fractions was subjected
      to reverse transcriptase polymerase chain reaction (RT-PCR) to detect estrogen
      receptor (ER) mRNA. The RT-PCR results demonstrated that ER mRNA was present in
      both LC and PLC fractions. Quantitative RT-PCR analysis, using rabbit beta-globin
      mRNA as the internal standard, showed that ER mRNA in the PLC fraction was 20
      fold higher than in the LC fraction in control testis. After EDS treatment, ER
      mRNA levels in the PLC fraction decreased and reached a nadir at Day 16
      posttreatment. Thereafter, ER mRNA in the PLC fraction gradually increased and
      returned to control PLC levels. In contrast, ER mRNA levels in the LC fraction in
      controls and at Days 16-45 posttreatment remained constant. To correlate the
      changes in ER mRNA levels with LC differentiation, in vitro testosterone (T)
      production by PLC- and LC-enriched fractions in the presence or absence of 50 mIU
      hCG was measured by RIA. T production in the control PLC fraction was low (1/10th
      that in the control LC fraction), and hCG addition resulted in only a 1.5-fold
      stimulation (relative to a 7.5-fold stimulation in LCs). In the PLC fraction, T
      production was not detectable at Days 2 and 10 after EDS treatments, began to
      respond to hCG stimulation with increased T production at Day 16, and reached a
      maximum between 4 and 6 wk after EDS treatment. By Day 60 posttreatment, T
      production in the PLC fraction decreased and returned to control PLC levels.
      Testosterone production in the LC fraction was not detectable at Days 2 and 10
      posttreatment. From Days 16 to 60 posttreatment, LC basal and hCG-responsive T
      production increased gradually and returned to control LC levels. It is concluded
      that functional LCs are regenerated from the PLCs and that both these cell types
      possess ER mRNA. It is interesting to note that PLCs exhibit higher levels of ER
      mRNA than do LCs. A decrease in ER mRNA in PLCs appears to coincide with the
      early differentiation process to yield LCs. Thus, estradiol-17 beta produced
      locally in the testis by the LCs might act via its receptor as a paracrine
      substance to impede PLC development into LCs. It is therefore possible that
      either a decrease in E2 production or a decrease in ER and its mRNA in PLCs would
      then release the PLCs to begin the regeneration process.

PMID- 8879491
TI  - Fertilization and development of mouse oocytes injected with isolated sperm
      heads.
AB  - To determine whether spermatozoa must be structurally intact before microsurgical
      injection into oocytes for normal fertilization, intact spermatozoa, as well as
      sperm heads separated from tails by sonication, were individually injected into
      oocytes. When whole spermatozoa were injected immediately after their
      immobilization, the majority of the oocytes were fertilized and developed
      normally. Sonication in the presence or absence of Triton X-100 decapitated more
      than 95% of spermatozoa. Although all decapitated spermatozoa were diagnosed as
      "dead" by live/dead sperm staining, separated sperm heads (nuclei) could
      participate in normal embryo development when injected into the oocytes. The
      ability of isolated sperm heads (nuclei) to participate in normal embryo
      development was maintained under cryopreservation conditions that were not
      suitable for the survival of plasma membrane-intact spermatozoa. These results
      indicate that 1) spermatozoa do not need to be structurally intact for
      intracytoplasmic injection, 2) the plasma and acrosomal membranes and all tail
      components are not essential for normal embryo development, at least in the
      mouse, and 3) the cryopreservation conditions required for maintenance of the
      genetic integrity of sperm nuclei are less stringent than those necessary for
      keeping plasma membrane-intact spermatozoa alive.

PMID- 8879492
TI  - Differential expression of beta transforming growth factors (TGF beta 1, TGF beta
      2, and TGF beta 3) and their receptors (type I and type II) in peri-implantation
      porcine conceptuses.
AB  - Beta transforming growth factors (TGF beta 1, TGF beta 2, and TGF beta 3) and
      type I and II TGF beta receptors were immunohistochemically localized in peri
      implantation porcine conceptuses (embryos and associated membranes) collected on
      Day 10 through Day 14 of gestation. Our results indicate specific
      immunolocalization of TGF beta isoforms and their receptors in conceptuses during
      these gestational days. In parietal endoderm, TGF beta 1 immunoreactions were
      weak to undetectable, TGF beta 2 immunoreactions were intense, and TGF beta 3
      immunoreactions were intermediate in intensity to TGF beta 2 and TGF beta 1. In
      contrast to immunoreactions in endoderm, TGF beta 1 and TGF beta 3 immunostaining
      in trophectoderm (Tr) was intense. Differences in TGF beta 2 immunostaining of Tr
      were observed from Days 10 to 14 of gestation. A drastic decrease in cytoplasmic
      immunostaining of ectoderm and mesoderm was detected from Days 12 to 14 for all
      TGF beta isoforms and type II receptor; however, type I receptor immunoreactions
      were consistently detected between Days 10 and 14. Concurrent expression of both
      type I and type II receptors in the peri-implantation conceptuses suggests that
      porcine conceptuses are capable of binding and responding to TGF beta s during
      this period. Differential expression of the three TGF beta isoforms suggests
      different roles for TGF beta s 1, 2, and 3 in conceptus development. Our results
      suggest possible roles for TGF beta s in early growth and differentiation of the
      embryo, differentiation of the Tr, and implantation.

PMID- 8879493
TI  - Insulin-like growth factor system in bovine first-wave dominant and subordinate
      follicles.
AB  - Estradiol (E2)-active (Day 5 [D5]), transitional E2-active (D8), atretic (D12 -
      1), and E2-sustained dominant follicles (DF, D12 + 1) and associated subordinate
      follicles (SF) were obtained through use of an experimental model described here.
      The ovary bearing the DF was surgically removed by colpotomy, and individual
      follicles were utilized to study changes in concentrations of insulin like growth
      factor-I (IGF-I) and -II (IGF-II) and changes in amounts and proportions of the
      different IGF-binding proteins (IGFBP) present in follicular fluid (FF). The
      ratio of FF E2 to progesterone (EPR) was utilized to classify follicles into E2
      active (EPR > 1) and E2 inactive (EPR < 1). The IGF-I and IGF-II concentrations
      in FF were similar among experimental groups and between DF and SF. Six different
      molecular mass bands (49, 43, 35, 30, 28, and 22 kDa) were detected by ligand
      blot in FF of DF and SF. Immunoprecipitation analysis identified four IGFBPs (-2,
      -3, -4, and -5) in FF. The 35-kDa band corresponded to IGFBP-2, the 49- and 43
      kDa bands to IGFBP-3, the 28- and 22-kDa bands to IGFBP-4, and the 30-kDa band to
      IGFBP-5. No IGFBP-6 was found by immunoprecipitation. Absolute amounts and
      proportions of low molecular mass IGFBPs (-2, -4, and -5) were increased with
      atresia of the DF and in SF compared to E2-active DF. Conversely, although
      absolute amounts of IGFBP-3 remained unchanged, their proportion in FF decreased
      in SF compared to DF. The ratio of IGF-I to IGFBPs decreased with atresia of the
      DF, possibly leaving less bioavailable IGF-I to increase FSH action at the level
      of the follicle.

PMID- 8879494
TI  - Purification and characterization of the active precursor of a human sperm
      motility inhibitor secreted by the seminal vesicles: identity with semenogelin.
AB  - Human seminal plasma contains a sperm motility inhibitor that originates from
      seminal vesicles as a precursor form. This precursor is degraded into smaller
      peptides by prostatic proteases shortly after ejaculation. The seminal plasma
      sperm motility inhibitor (SPMI) precursor was purified by a combination of cation
      exchange chromatography on S-Sepharose followed by C4 reverse-phase high
      performance liquid chromatography directly from seminal vesicle fluid or washed
      seminal coagulum. The purification procedure yielded a protein of apparent
      homogeneity, with a molecular mass of 52 kDa by SDS-PAGE. It migrated as a 105
      kDa protein by molecular sieving under denaturing conditions. The purified SPMI
      precursor was digested by the prostatic protease prostate-specific antigen (PSA),
      causing a 76 +/- 4% drop in biological activity and transformation into low
      molecular mass SPMI polypeptides (5-20 kDa) similar to those observed in
      liquefied semen. The N-terminal amino acid sequences of three degradation
      peptides were obtained by Edman degradation and found to correspond to residues
      45-50, 85-90, and 137-143 of semenogelin, a protein characterized as the major
      structural component of semen coagulum. The amino acid composition of SPMI
      precursor was found to be almost identical to that of semenogelin. Moreover, the
      mass of the precursor was estimated at 49,620 daltons by electrospray-ionization
      mass spectrometry, a value in close agreement with the expected mass of
      semenogelin according to its cDNA sequence. The SPMI precursor was found to
      inhibit sperm motility in a dose-dependent manner, with complete immobilization
      at 500 U/ml of SPMI. The motility of completely immobilized spermatozoa was
      partially recovered after washing of the cells. The results suggest that SPMI
      precursor is the major component of the seminal vesicle secretions and seminal
      coagulum. It can be degraded by PSA in a manner reminiscent of its processing in
      whole semen. Taken together these results indicate that the SPMI precursor is
      semenogelin and that intact semenogelin can immobilize spermatozoa.

PMID- 8879495
TI  - A comprehensive survey of the cadherins expressed in the testes of fetal,
      immature, and adult mice utilizing the polymerase chain reaction.
AB  - The cadherins are a family of calcium-binding membrane glycoproteins. Most
      cadherins are capable of acting as cell adhesion molecules (CAMs). In order to
      begin a thorough analysis of the roles of these CAMs in the testis, we employed a
      reverse transcriptase-polymerase chain reaction (RT-PCR) strategy to identify the
      cadherins expressed in this tissue at various stages of development.
      Oligonucleotides encoding amino acid sequences that are conserved among all of
      the known cadherins were used as primers in the RT-PCR, with cDNA preparations of
      fetal, newborn, 7-day, 21-day, and adult mouse testes employed as templates. The
      PCR products were subcloned into a plasmid vector and sequenced. On the basis of
      the nucleotide sequences of these PCR products, we have determined that five
      previously characterized cadherins (E-cadherin, N-cadherin, P-cadherin, K
      cadherin, and OB-cadherin), as well as two novel cadherins (T1-cadherin and T2
      cadherin), are expressed at various stages during testicular development. In
      order to determine the expression patterns of these cadherins, we ascertained the
      mRNA levels of each cadherin normalized to the levels of hypoxanthine
      phosphoribosyltransferase mRNA in fetal, newborn, 7-day, 21-day, and adult mouse
      testes. We observed that N-cadherin mRNA is expressed at all stages of testicular
      development, with maximal levels being present in the testes of 21-day-old mice.
      Furthermore, we found that E-, P-, K-, OB-, and T2-cadherin mRNAs are all
      expressed in the fetal gonad. The testicular levels of these cadherin mRNAs
      decreased dramatically after birth. Conversely, T1-cadherin mRNA was not detected
      in the fetal, newborn, and 7-day-old testes but was present in 21-day-old and
      adult testes. T1-cadherin levels were 10-fold higher in the testes of adult mice,
      compared to the levels found in the testes of 21-day-old mice. We speculate that
      these cadherins will be found to be intimately involved in mediating cell
      interactions during testicular development.

PMID- 8879496
TI  - Relationship between gonadotropin subunit messenger ribonucleic acid levels and
      plasma gonadotropin concentrations in intact and orchidectomized adult rats.
AB  - To gain further insight into the factors regulating FSH, LH, and uncombined alpha
      subunit secretion in the male rat, pituitary levels of the gonadotropin subunit
      mRNAs and plasma levels of FSH, LH, and alpha subunit were measured in 7-wk-old
      intact male rats and rats castrated 2 wk previously. A highly positive
      correlation was found between pituitary FSH beta mRNA levels and plasma FSH
      concentrations in intact (r = 0.60; p = 0.039) but not in castrated rats (r = 
      0.13; p = 0.66). On the other hand, neither pituitary alpha subunit nor LH beta
      mRNA levels were predictive of plasma alpha subunit or LH concentrations in
      intact or orchidectomized rats. This observation is consistent with the proposal
      that a pretranslational mechanism is the major determinant of FSH secretion in
      the intact adult male rat but not in the castrated male.

PMID- 8879497
TI  - Time-course of thyroid hormone involvement in the development of anestrus in the
      ewe.
AB  - It is well established that the thyroid gland is essential for termination of
      seasonal reproductive activity in a variety of birds and mammals. In the present
      study, we examined when during the breeding season the thyroid exerts this effect
      in female sheep. Previous results suggest that the presence of thyroid hormones
      during the first 4-6 wk (20-25%) of the breeding season is not sufficient for the
      neuroendocrine changes that lead to anestrus. We therefore hypothesized that
      thyroid hormone action is exerted at some point during the latter 75-80% of the
      breeding season. To test this hypothesis, ewes thyroidectomized early in the
      breeding season received replacement of thyroxine at various times to create gaps
      during the mid- to late breeding season when thyroid hormones were absent. We
      then examined the effect, if any, of this absence on development of seasonal
      neuroendocrine anestrus. Each ewe was ovariectomized and treated with a constant
      release Silastic capsule containing estradiol. Serum concentrations of LH were
      used as an index of seasonal changes in reproductive neuroendocrine activity. We
      found that when thyroid hormones were removed for a 60-day period in mid- to late
      breeding season (from mid-Oct. to late Dec., which is approximately 40% of the
      entire breeding season), anestrus still developed at the normal time. We
      conclude, therefore, that thyroid hormones need not be present for much of the
      breeding season (mid-Sept. through late Dec.) for anestrus to develop in the ewe.
      Rather, we postulate that thyroid hormones need to be present for only a brief
      period of time near the end of the breeding season for the neuroendocrine changes
      that lead to anestrus.

PMID- 8879498
TI  - Exogenous oxytocin stimulates uterine secretion of prostaglandin F2 alpha in
      cyclic and early pregnant swine.
AB  - Oxytocin (OT) stimulates endometrial secretion of prostaglandin (PG) F2 alpha
      around the time of corpus luteum regression in ruminants, but the stimulus for
      luteolytic PGF2 alpha release in cyclic pigs is not clear. We previously reported
      that OT stimulates endometrial phosphoinositide hydrolysis and PGF2 alpha release
      in vitro, and that exogenous OT administered on Days 10-16 caused a uterine
      dependent reduction in interestrous interval. In this study, the development of
      endometrial responsiveness to OT in cyclic, early pregnant, and ovarian-intact
      hysterectomized gilts was investigated. On Day 7 (onset of estrus = Day 0), 26
      gilts were fitted with indwelling jugular catheters, and 5 of these gilts were
      hysterectomized. Cyclic (n = 5), pregnant (n = 6), and ovarian-intact
      hysterectomized (n = 5) gilts received i.v. injections of 20 USP units OT
      (equivalent to 20 IU or 40 micrograms/ml) on Days 10, 12, 14, and 16; and cyclic
      controls (n = 5) and pregnant controls (n = 5) received i.v. injections of
      vehicle. Concentration of 13,14-dihydro-15-keto-PGF2 alpha (PGFM; the major
      stable metabolite of PGF2 alpha) was measured in jugular venous plasma collected
      at 10-min intervals, from 20 min before to 120 min after i.v. injections of OT or
      vehicle. Plasma progesterone was measured in blood samples collected daily from
      Day 9 through return to estrus (cyclic gilts) or through Day 30 (pregnant and
      hysterectomized gilts). Vehicle-treated and OT-treated cyclic gilts were not
      responsive to OT on Days 10 and 12, and had similar plasma PGFM profiles on these
      days. However, OT-treated cyclic gilts were responsive (p < 0.01) to OT on Days
      14 and 16, and peak concentrations of PGFM were detected in jugular plasma 10 min
      after OT injection. Concentrations of PGFM did not increase after vehicle
      injection on any day in controls. Similarly, PGFM in ovarian-intact
      hysterectomized gilts did not increase on any day after OT injection, indicating
      that the uterus was probably the source of OT-induced PGFM in cyclic gilts.
      Pregnant vehicle-treated gilts also did not have increased PGFM on any day after
      injection of vehicle. Pregnant OT-treated gilts had increased (p < 0.01) PGFM
      concentrations after OT injection on all days that were higher than
      concentrations in cyclic gilts on Days 10 and 12, but lower than those in cyclic
      gilts on Days 14 and 16 (p < 0.01). The concentration of plasma progesterone in
      cyclic gilts did not decrease until Days 15-16 (p < 0.01). Plasma progesterone
      was maintained in pregnant and hysterectomized gilts and was not influenced by OT
      treatment. These results indicated that 1) endometrial responsiveness to OT in
      cyclic gilts developed between Days 12 and 14 postestrus, 2) endometrial
      responsiveness to OT developed before luteolysis was initiated, and 3)
      endometrial responsiveness to OT in pregnant pigs developed before Day 10 of
      pregnancy and was attenuated on Days 14 through 16. These results are consistent
      with the hypothesis that OT may promote pulsatile luteolytic secretion of PGF2
      alpha during corpus luteum regression in swine and that responsiveness to OT was
      suppressed to maintain corpus luteum function during early pregnancy.

PMID- 8879499
TI  - Application of urinary and fecal steroid measurements for monitoring ovarian
      function and pregnancy in the bonobo (Pan paniscus) and evaluation of perineal
      swelling patterns in relation to endocrine events.
AB  - Estrone conjugates (E1C), pregnanediol glucuronide (PdG), and estriol (E3) in
      urine, and immunoreactive E1C, E3, pregnanediol (Pd), and progesterone (P4) in
      feces were determined along with records of perineal sex skin swelling throughout
      7 nonconception cycles and 3 full-term pregnancies of 4 adult female bonobos (Pan
      paniscus). A typical preovulatory urinary E1C surge and postovulatory increase in
      urinary PdG were seen during the menstrual cycles. Fecal progestin levels were
      significantly correlated with those of PdG in urine in all cycles, while E1C
      measurements in feces were significantly correlated with those in urine in only 3
      cycles. On the basis of hormone profiles, a variable follicular phase of 17-40
      days and a relatively constant luteal phase of 11-15 days was found, resulting in
      cycle lengths of 31-51 days. All urinary and fecal hormones were markedly
      elevated during pregnancy. Measurement of E1C in both urine and feces was most
      useful for early pregnancy diagnosis, while E3 was of value in confirming
      pregnancy and assessing fetal viability. The period of perineal swelling during
      the cycle comprised on average 66.3% of cycle length, half of which was
      associated with a phase of maximum tumescence. Ovulation usually occurred within
      the maximum swelling phase, but timing of ovulation within this period was highly
      variable and was more closely associated with the end rather than the onset of
      maximum tumescence. The data presented here are of great practical value in the
      captive breeding management of bonobos and offer new opportunities for
      investigating basic questions of bonobo reproductive biology both in captivity
      and in the wild.

PMID- 8879500
TI  - Progesterone and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) in the pregnant
      baboon: selective placental secretion of 20 alpha-OHP into the fetal compartment.
AB  - The serum concentrations of progesterone and 20 alpha-hydroxypregn-4-en-3-one (20
      alpha-OHP) were measured by RIA in blood draining the maternal and fetal sides of
      the placenta on Day 100 and Day 170 of gestation (term = Day 184) in the baboon
      to determine the qualitative and quantitative patterns of progestins within the
      maternal-placental-fetal compartment and to ascertain whether production of
      placental progestins is increased with advancing gestation. The mean (+/- SEM)
      concentration of progesterone in maternal serum was similar at mid- (10 +/- 2
      ng/ml) and late (11 +/- 3 ng/ml) gestation and not different than that of 20
      alpha-OHP (6 +/- 1 ng/ml). In the uterine vein, progesterone levels were greater
      (p < 0.05) at Day 100 (82 +/- 13 ng/ml) than at Day 170 (30 +/- 7 ng/ml) and
      exceeded (p < 0.05) those of 20 alpha-OHP at both mid- (8 +/- 2 ng/ml) and late
      (4 +/- 1 ng/ml) gestation. Progesterone concentrations in the umbilical vein (128
      +/- 24 ng/ml) and artery (79 +/- 12 ng/ml) at midgestation exceeded respective
      values at term (20 +/- 1 and 14 +/- 1 ng/ml). In contrast, 20 alpha-OHP
      concentrations in the umbilical vein (17 +/- 4 ng/ml) and artery (12 +/- 3 ng/ml)
      at midgestation increased more than 2-fold by Day 170. The estimated secretion
      rate of placental progesterone into the fetus was similar at mid- (752 +/- 154
      ng/min) and late (681 +/- 171 ng/min) gestation, whereas that for 20 alpha-OHP
      was negligible at midgestation (57 +/- 71 ng/min) and increased 15-fold (p <
      0.05) by term (892 +/- 241 ng/min). Because 20 alpha-OHP is a metabolite of
      progesterone, total placental progesterone production was greater (p < 0.05) at
      term (1595 +/- 400 ng/min) than at midgestation (809 +/- 171 ng/min). This study
      demonstrates that placental secretion of progesterone is bidirectional whereas
      that of 20 alpha-OHP occurs selectively into the fetus. Although progesterone and
      20 alpha-OHP levels in the fetus were lower at term than at midgestation, because
      of the developmental increase in umbilical blood flow as determined by others,
      placental progesterone production was actually increased during this interval.
      Therefore, we suggest that the estrogen-dependent developmental increase in key
      components of the progesterone biosynthetic pathway, recently demonstrated by us
      in the baboon placenta, is associated with a corresponding increase in
      progesterone production.

PMID- 8879501
TI  - [3H]heparin binding in boar spermatozoa: characterization and correlation with
      routine semen quality parameters.
AB  - A simple technique has been established for the purpose of characterizing heparin
      binding to boar sperm. Binding experiments were performed using [3H]heparin and
      extended boar semen. [3H]Heparin binding to boar sperm was effectively displaced
      by increasing concentrations of heparin. [3H]Heparin binding was linear at least
      between 50,000 and 10(6) spermatozoa and was stable for at least 120 min. Binding
      was sensitive to fucoidan, chondroitin sulfate B, chondroitin sulfate C, and
      chondroitin sulfate A, while keratan sulfate had only a marginal effect on
      binding. The [3H]heparin binding was saturable. Assuming a 13,000 M(r) for the
      [3H]heparin used, binding to boar spermatozoa showed an apparent equilibrium
      dissociation constant (Kd) of 23.6 +/- 2.5 nM and a maximum binding capacity
      (Bmax) of 6.0 +/- 1.1 pmol/10(6) spermatozoa (average values from 6 boars, means
      +/- SEM). Interejaculate variations in binding parameters were dependent on the
      male. Thus, with respect to Bmax variation, 4 of 6 boars studied exhibited an
      interejaculate coefficient of variation of less than 0.33 (0.09, 0.11, 0.11, and
      0.29, respectively, for 3 consecutive ejaculates), while in the case of Kd
      interejaculate variation, only 2 of the 6 boars studied showed acceptable
      variation coefficients (0.16 and 0.28). No seasonal effect was observed in either
      of the binding parameters, with the variations following boar-specific patterns.
      Kd and Bmax intermean differences for different boars during the course of the
      study period (April-June) were not significant (p > 0.05). Correlations of mean
      boar binding parameters (Kd and Bmax) with conventional semen quality parameters
      showed a correlation between Bmax values and those of the osmotic resistance test
      (r = 0.8990, p < 0.01), normal acrosomes (r = 0.7946, p < 0.05), and bended tails
      (r = -0.8632, p < 0.02). Kd values were correlated with cytoplasmic distal
      droplet (r = -0.7992, p < 0.05). The glycosaminoglycans and polysulfated boar
      sperm binding sites reported in the present work should be regarded as binding
      sites until further studies elucidate their physiological role. The results
      obtained suggest that this technique be given a role as a research tool.

PMID- 8879502
TI  - Expression of the steroidogenic acute regulatory protein in the corpus luteum of
      the rabbit: dependence upon the luteotropic hormone, estradiol-17 beta.
AB  - The recent characterization of the mitochondrial protein, Steroidogenic Acute
      Regulatory (StAR) protein, as a rate-limiting protein in steroidogenesis prompted
      us to investigate whether StAR is expressed in the rabbit corpus luteum and
      whether the expression of StAR is responsive to estradiol-17 beta, the
      luteotropic hormone in the rabbit. In rabbits treated continuously with exogenous
      estradiol through Day 13 of pseudopregnancy (n = 9), immunoblot analysis revealed
      that luteal expression of StAR was stable, ranging from 8.5 to 9.7 U of corrected
      integrated optical density. Plasma progesterone concentration (mean +/- SEM)
      remained elevated in these rabbits (14.3 +/- 2.1 ng/ml). In contrast, expression
      of StAR decreased in corpora lutea of rabbits deprived of estradiol for the last
      48 and 72 h of the experiment (4.9 +/- 2.2 and 0.3 +/- 0.2 U, respectively, n = 3
      per group), and was associated with a decline in plasma progesterone (0.8 +/- 0.1
      and 0.5 +/- 0.3 ng/ml, respectively). Replacement of estradiol after 48 h of
      estradiol deprivation (n = 3) stimulated the reappearance of StAR (10.3 +/- 2.6
      U) and the restoration of plasma progesterone (10.4 +/- 4.9 ng/ml).
      [35S]Methionine labeling of proteins in rabbit corpora lutea revealed that
      several isoforms of StAR protein were specifically synthesized in response to
      estradiol treatment. Collectively, these observations are consistent with a
      proposed role for StAR in the mediation of the luteotropic effect of estrogen to
      promote the synthesis of progesterone in the rabbit.

PMID- 8879503
TI  - Natural and induced ovarian synchrony in golden lion tamarins (Leontopithecus
      rosalia).
AB  - Ovarian cycle synchrony was assessed in spontaneously cycling female golden lion
      tamarins by monitoring longitudinal (16 mo) urinary steroid metabolite (estrone
      conjugates; pregnanediol-3 alpha-glucuronide, PdG) excretion in four pairs (n =
      8) of females isolated from males. The overall mean ovarian cycle duration was
      18.5 +/- 0.3 days (n = 136 cycles; mean range, 15.7-21.0 days), and there was no
      evidence of reproductive seasonality. Laparoscopic ovarian examinations confirmed
      that cyclic fluctuations in urinary steroid metabolite excretion were temporally
      associated with the formation and demise of corpora lutea. Evaluation of ovarian
      synchronization tested the null hypothesis that urinary hormone cycles were
      expressed randomly relative to those of cagemates or other females housed in
      separate cages but within close proximity. Natural ovarian synchrony (expressed
      as the mean difference in ovarian cycle onset) between cagemates (4.1 +/- 0.4
      days) and among noncagemates (4.2 +/- 0.2 days) did not differ (p > 0.05) from a
      random ovarian cycle distribution. Two trials also were conducted to evaluate the
      efficacy of the prostaglandin (PG) F2 alpha analogue, cloprostenol, for
      artificially synchronizing ovarian cycles. Induced ovarian synchrony was not
      achieved with a single 0.8-microgram i.m. injection of cloprostenol. However,
      doubling the cloprostenol dose (1.6 micrograms) caused a rapid decrease in mean
      urinary PdG (p < 0.05) within 2 days, and synchronous ovulation was demonstrated
      by an increase (p < 0.01) in mean urinary PdG 10 days after cloprostenol
      administration. In summary, females housed in pairs, in the absence of males,
      exhibit spontaneous, year-round ovarian cycles with no evidence of among-female
      ovarian synchrony. Results also suggest that this New World primate has a reduced
      sensitivity to cloprostenol (compared to common marmosets) but that a single,
      midcycle cloprostenol injection of 1.6 micrograms effectively induces luteolysis
      and synchronous ovulation.

PMID- 8879504
TI  - Exogenous interferon delays luteal regression in red deer hinds (Cervus elaphus)
      by suppressing steroid-induced endometrial oxytocin sensitivity.
AB  - Three groups of intact hinds (n = 10-18) and one group of ovariectomized hinds
      were treated with progesterone by mean, of Controlled Internal Drug Releasing
      (CIDR) devices for 13 days (device removal = Day 0). Group 1 served as controls;
      group 2 received injections of 4 mg recombinant bovine interferon-alpha,1 twice
      daily from Days 13 to 21; group 3 was run with a stag from Days 0 to 3, and all
      hinds were subsequently diagnosed pregnant; group 4 (ovariectomized) was treated
      with CIDR devices and estradiol to mimic steroid secretion during the estrous
      cycle. Progesterone profiles were determined from thrice-weekly plasma samples
      from Days -13 to 28. Rectal temperature was measured in a subset of groups 1 and
      2 from Days 9 to 21. Oxytocin-induced prostaglandin F2 alpha release was measured
      in a subset of groups 1, 2, and 4 on Days 2, 4, 10, 16, and 18. Data are
      presented as means +/- SEM. Exogenous interferon delayed luteolysis (> or = 28
      vs. 21.2 +/- 0.55 days, P < 0.0005) and induced transient pyrexia after the first
      injection (39.89 +/- 0.11 vs. 38.88 +/- 0.19 degrees C, p < 0.0005). Incidence of
      oxytocin-induced PGF2 alpha release in control hinds was greater on Days 2 and 18
      than on Days 4 and 10 (8/8 and 7/8 vs. 3/8 and 0/8, respectively; p < 0.05) and
      was greater in control than in interferon-treated hinds on Days 16 and 18 (5/8
      and 7/8 vs. 1/8 and 1/8, respectively; p < 0.05). Profiles of plasma progesterone
      concentration and oxytocin sensitivity in steroid-treated ovariectomized hinds
      did not differ from those in control hinds. These results suggest that steroid
      controlled uterine oxytocin sensitivity is important in luteolysis and is
      suppressed by the administration of interferon, the putative embryonic pregnancy
      recognition signal in red deer.

PMID- 8879505
TI  - Characterization of prostaglandin F2 alpha production in pregnant and cycling
      mice.
AB  - To clarify the regulation of prostaglandin F2 alpha (PGF2 alpha) production in
      vivo in mice during pregnancy and the estrous cycle, we injected [3H]PGF2 alpha
      i.v. into female mice and determined the structures of three urinary metabolites
      by gas chromatography-mass spectrometry. The compounds were 5,7,11-trihydroxy
      tetranor-prosta-9-enoic acid (FUM-I), 5,7,11-trihydroxy-tetranor-prostanoic acid
      (FUM-II), and 5,7-dihydroxy-11-keto-tetranor-prostanoic acid (FUM-III). The major
      metabolite, FUM-III, increased four-fold at the term of pregnancy and transiently
      during diestrus of the estrous cycle. Consistent with the increase in FUM-III,
      immunoblot analysis with anti-bovine PGF synthase antiserum demonstrated that a
      36-kDa protein band corresponding to PGF synthase increased in the uterus at late
      pregnancy and during diestrus. These results suggest that PGF2 alpha production
      may increase at term and change during the estrous cycle and is associated with
      an increase in uterine PGF synthase concentrations.

PMID- 8879506
TI  - Testosterone withdrawal promotes stage-specific detachment of round spermatids
      from the rat seminiferous epithelium.
AB  - Testosterone (T) has been shown to be essential for the completion of
      spermiogenesis. Our previous studies showed that when intratesticular T was
      suppressed for 11 wk, the conversion of round spermatids between stages VII and
      VIII of the spermatogenic cycle was markedly suppressed and that elongated
      spermatids were undetectable. The fate of the round spermatids that did not
      proceed through this conversion was unclear. The current study aimed to
      investigate this T-dependent loss of round spermatids during stages VII and VIII.
      Adult male Sprague-Dawley rats received 24-cm T implants for 1 wk to suppress LH
      while maintaining spermatogenesis. The T24 implants were removed and replaced
      with 3-cm T plus 0.4-cm estradiol (TE treatment) to suppress intratesticular T
      and spermatogenesis, and animals were killed at 0 and 4 days and 1, 2, 3, 4, and
      6 wk later. The number of homogenization-resistant elongated spermatids in the
      testis was counted, and round spermatid populations in stages VII and VIII were
      quantified using stereological techniques. The hourly production rates (HPR) were
      calculated, and a ratio was made between the HPR of round spermatids in stages
      VII and VIII to assess the efficiency of their conversion through these stages.
      Testicular T levels were suppressed to 2-4% of control values by TE treatment.
      After 2 wk of TE treatment, the number of homogenization-resistant elongated
      spermatids was significantly suppressed, falling to < 0.5% of the control value
      by 6 wk. The HPR of round spermatids in stages VII and VIII was not affected by
      up to 2 wk of TE treatment, nor was the conversion between these stages
      interrupted. After 3 wk of TE treatment, the HPR of round spermatids in stages
      VII and VIII was significantly suppressed, as was the conversion between these
      stages, the ratio falling to 27% of the control value by 6 wk. In rats treated
      with TE, histological examination of the cauda epididymidis showed occasional
      round spermatids after 3 wk of treatment, and large numbers after 6 wk. We
      conclude that the failure of round spermatids to complete spermiogenesis
      following T withdrawal is due to stage-specific detachment of round spermatids
      between stages VII and VIII.

PMID- 8879507
TI  - Steady-state luteinizing hormone receptor messenger ribonucleic acid levels and
      endothelial cell composition in bovine normal- and short-lived corpora lutea.
AB  - The short-lived corpus luteum (CL) contributes to reproductive inefficiency
      during the postpartum period in beef cows. The cause for the early demise of the
      short-lived CL is not fully understood but is believed to involve a premature
      release of prostaglandin F2 alpha. The objectives of this study were to evaluate
      norgestomet-hCG-induced normal-lived CL and hCG-induced short-lived CL in
      postpartum cows with respect to serum progesterone (P4) and 13,14-dihydro-15
      keto, prostaglandin F2 alpha (PGFM) concentrations and luteal LH receptor (LH-R)
      concentrations, LH-R mRNA levels, and vascularity. Although serum P4 profiles
      from the time of hCG administration (Day 0) until luteectomy (Day 6, 7, or 8)
      were similar between CL life span groups, PGFM concentrations were elevated (p <
      0.05) on Day 8 in cows expected to have short-lived CL compared to normal-lived
      CL. The LH-R concentrations were similar between normal- and short-lived CL on
      all days measured. Irrespective of luteal life span and day of luteectomy, all CL
      possessed a 4.4-kb LH-R transcript. Actin-normalized LH-R mRNA levels were
      similar between normal- and short-lived CL on Days 6 and 7; however, Day 8 short
      lived CL contained less (p < 0.05) LH-R mRNA than Day 8 normal-lived CL. Although
      the area of luteal tissue occupied by capillaries in normal- and short-lived CL
      was similar on Days 6 and 7, the area occupied by capillaries in short-lived CL
      was lower (p < 0.05) than that for normal-lived CL on Day 8. Collectively, these
      results indicate that there is a decrease in steady-state LH-R mRNA and a
      reduction in luteal vascularity in CL expected to be short-lived. These changes
      occur concomitantly with a rise in serum PGFM, but prior to a decline in serum
      P4.

PMID- 8879508
TI  - Effects of transient prepubertal 6-N-propyl-2-thiouracil treatment on testis
      development and function in the domestic fowl.
AB  - It has been well established that thyroid hormones play an important role in
      regulating the onset of puberty and reproductive function in birds. In mammals it
      has been shown that transient hypothyroidism induced with the reversible
      goitrogen 6-N-propyl-2-thiouracil (PTU) can result in tremendous increases in
      testis size and sperm production and that the timing of hypothyroidism must
      correspond to the period of Sertoli cell proliferation. As the period of Sertoli
      cell proliferation is not precisely known in the fowl, an experiment was
      conducted to determine whether chicken testes have a similar window of
      sensitivity to PTU treatment. Broiler breeder male chicks (Peterson) were placed
      in floor pens at one day of age and reared according to the breeder's management
      guide for the entire 28-wk duration (controls) or up to the point of dietary
      treatment with PTU (0.1% w:w) for 6 wk that began at 2-wk intervals (2-8, 4-10, 6
      12, 8-14, and 10-16 wk of age); after treatment, birds were returned to feed
      restriction and photostimulated at 20 wk of age. Birds were bled and killed, and
      testes were collected at 4-wk intervals. At 28 wk, one testis was fixed for
      histological examination and one was immediately placed in liquid N2 for sperm
      counts. Treatment with PTU from 6 to 12 wk of age resulted in a 96% increase in
      mean testis weight at 28 wk of age (treated 39.3 +/- 4.1 g per testis vs. control
      20.0 +/- 1.6 g per testis). These testes exhibited normal morphology and
      increased relative sperm production. Treatment with PTU from either 8 to 14 or 10
      to 16 wk of age resulted in approximately a 35% increase in testis mass at 28 wk
      of age relative to the control value (27.2 +/- 2.0 g and 27.7 +/- 3.6 g vs. 20.0
      +/- 1.6 g per testis, respectively). However, both of these groups clearly
      demonstrated precocious puberty and abnormal spermatogenesis. These results
      suggest that appropriately timed PTU treatment may result in permanent increases
      in testis size and sperm production in the domestic fowl.

PMID- 8879509
TI  - Glucose participates in sperm-oocyte fusion in the mouse.
AB  - Glucose metabolism is necessary for successful fertilization in the mouse, but
      the precise step of this process that requires glucose has not been determined.
      In this study we have investigated the involvement of glucose in the gamete
      binding and fusion process. The relationship between the metabolism of this
      carbohydrate in the oocyte and this particular step of fertilization has also
      been studied. A binding and fusion assay was performed by inseminating zona-free
      oocytes with capacitated sperm. Sperm binding and the fusion reaction were
      assessed by counting the sperm bound to the oolemma and the sperm heads
      decondensed in the ooplasm, respectively. To determine the importance of glucose
      metabolism, nonmetabolized glucose analogues (L-glucose, 2-deoxyglucose, 3-O
      methylglucose) were used instead of glucose. The binding/fusion assay was also
      performed in the presence of glucose uptake inhibitors (cytochalasin B,
      phloretin, phlorizin). We have obtained evidence that glucose was specifically
      required for sperm penetration into zona-free oocytes (gamete fusion) but not for
      sperm binding to the oolemma. The metabolism of this carbohydrate appears to be
      essential, since nonmetabolized glucose analogues were unable to support this
      process. Although glucose metabolism was detectable in the oocyte, it did not
      appear to be related to the gamete fusion function. We hypothesize that the male
      gamete, which utilizes glucose as an energy substrate for various functions, may
      have a specific need to metabolize this hexose during fusion and incorporation
      within the oocyte.

PMID- 8879511
TI  - Gamma sterilization of UHMWPE articular implants: an analysis of the oxidation
      problem. Ultra High Molecular Weight Poly Ethylene.
AB  - Gamma irradiation of Ultrahigh Molecular Weight Polyethylene (UHMWPE) leads to
      long-lived free radicals which react with oxygen. Diffusion of oxygen, occurring
      over months or years, controlled by the permeability characteristics of the
      polymer, results in progressive oxidation, breaking of polymer chains, alteration
      of the crystalline portion of the polymer, and deterioration of the mechanical
      properties of the polymer. This paper reviews the observations in the literature
      on this issue and then presents a conceptual model concerning the interplay of
      radical diffusion, oxygen diffusion, non-uniform permeability, and free-radically
      driven chain reactions in order to explain these observations. The suggested
      model is based on literature that is available on the oxidation of linear
      polyethylenes during and after irradiation. The model directs the attention of
      researchers in the field of orthopaedic implants to the complexity of the process
      and the variety of issues and parameters to be considered while studying the long
      term effects of radiation sterilization on UHMWPE.

PMID- 8879510
TI  - Refinement of the differentiated phenotype of the spermatogenic cell line GC
      2spd(ts)
AB  - A transformed spermatogenic cell line GC-2spd(ts), recently reported to express a
      protein marker of spermiogenesis, was tested for the presence of several mRNAs
      encoded by genes transcribed specifically in the testis and at precise stages of
      spermatogenesis. Northern blotting and reverse-transcriptase polymerase chain
      reaction techniques showed that mRNAs for the stage-specific marker proteins LDH
      C4 (preleptotene), acrosin (premeiotic), protamine-2 (postmeiotic), and SP-10
      (postmeiotic round spermatid stage) were not detected in GC-2spd(ts) cells. Flow
      cytometric analysis of GC-2spd(ts) failed to detect a peak indicative of the
      presence of haploid chromosomes. Furthermore, the HS-63 monoclonal antibody,
      employed in an earlier report to demonstrate putative proacrosomal granules,
      failed to recognize the SP-10 protein in extracts of human or mouse sperm or in
      GC-2spd(ts) cells and instead recognized proteins of different masses. In view of
      interest in this line as a model for analyzing molecular events of
      spermatogenesis, this refinement of the GC-2spd(ts) phenotype may aid others
      considering these cells for studies of terminal stages of sperm differentiation.

PMID- 8879512
TI  - Polymethylmethacrylate composites: disturbed bone formation at the surface of
      bioactive glass and hydroxyapatite.
AB  - The effects of polymethylmethacrylate on bone formation were studied alone and as
      composites in combination with hydroxyapatite and bioactive glass in the rabbit
      subchondral femur. Radiographs, histology, computer assisted histomorphometry,
      scanning electron microscopy and energy dispersive X-ray analysis were used for
      evaluation. A total of 60 cones were implanted for 3, 6 and 12 weeks. The
      composite cones consisted of granules of bioactive glass (S56.5P4) or
      hydroxyapatite embedded in polymethylmethacrylate. Pure polymethylmethacrylate
      cones served as controls. At the interface of the cones, bone contact was
      observed only when bioactive glass or hydroxyapatite was present at the cone
      surface. Fibrous tissue was always found at the polymethylmethacrylate-tissue
      interface. The osteoconductive bone formation at the surface of bioactive glass
      and hydroxyapatite was disturbed by polymethylmethacrylate. It seemed to resist
      bone formation at the interface of both bioactive glass and hydroxyapatite.
      However, bioactive glass was better able to withstand the detrimental effect of
      polymethylmethacrylate than hydroxyapatite.

PMID- 8879513
TI  - Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate
      implants.
AB  - In this experimental study, blocks of natural coral (calcium carbonate) and its
      structurally similar derivate in the form of hydroxyapatite (calcium phosphate)
      were implanted in rat latissimus dorsi muscle with autogenous bone marrow to
      compare their bone-forming capability. A block without marrow placed in the
      opposite latissimus muscle served as a control. The animals were killed at 3, 6
      and 12 weeks and, in the hydroxyapatite group, also at 24 weeks. The sections
      were analysed histologically and histomorphometrically. Bone was found only in
      implants containing bone marrow. Bone formation was significantly (p < 0.05)
      higher in coral than in hydroxyapatite implants at 3 weeks (10.8% versus 4.8%)
      and at 12 weeks (13.7% versus 6.3%, bone/total original block area). At 12 weeks
      all the coral implants had lost their original structure, and the cross-sectional
      area of the block had diminished to 40% of the original area.

PMID- 8879514
TI  - Clinical and histologic aspects of biphasic calcium phosphate ceramic (BCP) used
      in connection with implant placement.
AB  - A granulate of biphasic calcium phosphate ceramic (BCP), composed of 50%
      hydroxyapatite and 50% beta-tricalcium phosphate, was used, in man, to fill
      defects resulting from cyst enucleation. The defects were covered with e-PTFE
      membranes, and at the re-entry procedure after six months, it was possible to see
      that the defects were filled by a newly formed tissue with the macroscopic
      features of mature bone. Smooth titanium implants were inserted in the newly
      regenerated tissue. Histological examination of this tissue showed that most of
      the particles were lined by newly formed bone. Some particles were undergoing
      resorption processes and were being gradually substituted by newly formed bone.
      No inflammatory infiltrate was present. Our results point, in conclusion, to a
      good biocompatibility and osteoconductivity of this material.

PMID- 8879515
TI  - Differences of bone bonding ability and degradation behaviour in vivo between
      amorphous calcium phosphate and highly crystalline hydroxyapatite coating.
AB  - Three types of calcium phosphate coating were formed on polyethersulphone (PES)
      rectangular plates using a biomimetic method: a 20 microns thick amorphous
      calcium phosphate (ACP 20) coating, a 50 microns thick amorphous calcium
      phosphate (ACP 50) coating, and a 50 microns thick highly crystalline
      hydroxyapatite (hHA 50) coating. Uncoated PES plates were used as a control
      group. These materials were implanted in the tibiae of rabbits and subcutaneously
      in rats, and the samples were harvested 8 and 16 weeks thereafter, and were
      examined histologically. The tensile failure loads at the bone-implant interfaces
      were determined using the detaching test. Each ACP coating was more degradable
      than the hHA 50 coating. However, newly formed bone came into direct contact with
      underlying materials as the coating degraded. No coating degraded in subcutaneous
      tissue. Soft tissue intervening was seen in uncoated samples. Failure load of ACP
      20-, ACP 50- and hHA 50-coated samples were all relatively higher than that of
      the uncoated samples at each period. Significant increase of failure load was
      seen in hHA 50-coated samples by 16 weeks, however, no increase was seen in
      either the uncoated or ACP-coated samples. If coating longevity is desired, then
      the hHA coating is preferable. However, if only the osteoconducive property of
      calcium phosphate coating is desired for initial fixation of porous materials,
      the ACP coating may be advantageous.

PMID- 8879516
TI  - Immunohistochemical studies on the distribution of albumin, fibrinogen,
      fibronectin, IgG and collagen around PTFE and titanium implants.
AB  - Time-dependent distribution of extracellular proteins (albumin, fibrinogen,
      fibronectin, collagen-I and IgG) in the interface zone between implant and soft
      tissue has been investigated utilizing a recently developed method. Commercially
      pure (c.p.) titanium and polytetrafluoroethylene (PTFE) implants were inserted in
      the abdominal wall of rats for 1, 6 and 12 weeks followed by a mild fixation,
      cryoprotection, rapid freezing in LN2-cooled propane, cryosubstitution and low
      temperature infiltration with UV curing of the methacrylate LR-Gold. Before
      sectioning, the bulk part of the titanium was removed by an electrolytical
      dissolution technique (electropolishing), while the PTFE implants were removed by
      a fracture technique. Employing a cryosubstitution method combined with
      postembedding immunohistochemistry, a light microscopic analysis was allowed. The
      selected proteins had an apparently varying distribution in the implant-close
      tissue and their distribution changed during the follow-up period. There was also
      a difference in the distribution pattern for each protein around titanium and
      PTFE implants. Insertion of the c.p. titanium implants elicited an inflammatory
      reaction in many respects similar to a normal wound healing response, while the
      PTFE implants caused a more pronounced, persistent inflammation.

PMID- 8879517
TI  - Sintering of partially-stabilized zirconia and partially-stabilized zirconia
      hydroxyapatite composites by hot isostatic pressing and pressureless sintering.
AB  - In this study two sintering techniques, pressureless sintering (PS) and hot
      isostatic pressing (HIP), were used for comparing the sinterability of two yttria
      partially-stabilized zirconia/hydroxyapatite (PSZ/HA) composites. Virtually dense
      ceramics were obtained using HIP at a maximum pressure of 160 MPa for 1 h at 1225
      degrees C for both PSZ powders and their HA composites. The ceramic bodies,
      produced using PS at the same temperature as in the HIP process and higher, had
      densities from 80% to 97% of theoretical density, depending on the properties of
      the PSZ powders. FTIR spectra of composites sintered by HIP and PS at 1225
      degrees C were compared, indicating a degradation of HA by PS but no degradation
      by HIP. The bending strength of HIPed ceramics was measured and found to be high.
      It is concluded that it is possible to produce dense PSZ/HA composites by the HIP
      or PS processes. For the PS, the reactivity of powders is the key factor during
      the densification. The HIP technique is the preferable technique for producing
      stable and dense HA-containing composites.

PMID- 8879518
TI  - Effect of polyvinyl chloride plastic on the growth and physiology of human
      umbilical vein endothelial cells.
AB  - In this work, human umbilical vein endothelial cells were cultured on common
      polystyrene cell culture plates, referred to as control plates, as well as on
      soft polyvinyl chloride plastics (PVC). Growth of human umbilical endothelial
      cells (HUVEC) on PVC coated with gelatin, collagen A and heparin plasma was
      significantly less than that on the control plates coated with the same substance
      or fibronectin. Cells cultured on PVC produced up to four times as much tissue
      plasminogen activator than control cells. With reference to plasminogen activator
      inhibitor 1 (PAI-1), more PAI-1 was released from cells grown on PVC than from
      those on the control plates coated with gelatin and collagen A. After endotoxin
      stimulation, the PAI-1 release of HUVEC cultured on PVC was significantly higher
      than that of control cells with the exception of cells grown on the fibronectin
      coated PVC that showed no difference. It is concluded that the type of plastic
      and coat used to culture HUVEC play a definite role in their growth and function.

PMID- 8879519
TI  - New polyurethane compositions able to bond high amounts of both albumin and
      heparin. II: Copolymers and polymer blends.
AB  - Haemocompatible new urethane copolymers and polymer blends containing, in the
      chain extender, a long chain alkyl group (able to bond albumin) or a tertiary
      ammonium group able, after suitable quaternization reaction, to bind ionically
      significant amounts of heparin, were prepared. The copolymers were characterized
      by differential scanning calorimetry, intrinsic viscosity determinations,
      infrared spectroscopy and nuclear magnetic resonance (1H and 13C). Biological in
      vitro evaluation has shown that the adsorption sequence for albumin and heparin,
      respectively, onto films of the various copolymers and blends, exerts a great
      influence. From scanning electron microscopy measurements it was seen that the
      bonding type of albumin to the polymer films plays a determining role on the
      platelet activation. A phase segregation occurring on the polymer blends surface
      was demonstrated by X-ray photoelectron spectroscopy measurements.

PMID- 8879520
TI  - Studies on radio-opaque polymeric biomaterials with potential applications to
      endovascular prostheses.
AB  - A new polymeric biomaterial, which uniquely combines radio-opacity (X-ray
      visibility) and low thrombogenicity, is described. First, preparation,
      purification, and identification of the essential monomeric building block, 2-[2'
      iodobenzoyl]-ethyl methacrylate (3), are outlined. Second, [Figure: See text] the
      synthesis of the biomaterial, a terpolymer with composition MMA: HEMA: 3 =
      65:15:20 (mole/mole/mole) is described. Third, the physico-chemical
      characteristics of the polymer (e.g. NMR spectroscopy, thermal behaviour) are
      given. Fourth, the in vitro thrombogenicity of the material was characterized by
      means of recent test assay. The combined results reveal that the terpolymer is
      very suitable for prosthetic applications in the cardiovascular system. A new
      prototype of an endovascular stent, made from the terpolymer, is presented.
      Stents find clinical use in interventional cardiology, in conjunction with
      percutaneous transluminal coronary angioplasty (PTCA). It is put forward that the
      stent prototype presented herein has, at least in principle, some advantages over
      existing (metallic) stents; these advantages are primarily owing to the unique
      combination of X-ray visibility and haemocompatibility which is presently
      achieved.

PMID- 8879521
TI  - New preparation and microstructure of the EndoPatch elastin-collagen containing
      glycosaminoglycans.
AB  - Several improvements of the basic reaction between elastin-solubilized peptides
      and type I + III collagens are presented. They concern the prior incubation of
      the proteins in an adequate medium as well as the addition of heparan sulphate or
      hyaluronic acid (HA) and the consequent effects on the physical properties of
      yielded matrices. The addition of HA in small amounts enabled us to make
      membranes with good performances.

PMID- 8879522
TI  - Three-dimensional composite of demineralized bone powder and collagen for in
      vitro analysis of chondroinduction of human dermal fibroblasts.
AB  - Implantation of demineralized bone powder (DBP) in muscle or connective tissue
      stimulates chondrogenesis followed by ectopic bone formation, in this way
      inducing the differentiation of endochondral bone. A new 3-dimensional in vitro
      composite sponge was designed to duplicate the packing density of in vivo DBP
      implants. The composite device, which consists of DBP packed between two layers
      of a porous collagen lattice, was used to assess the chondroblastic
      differentiation of human dermal fibroblasts. Important design considerations for
      this device were biocompatibility, rigidity and ability of cells to penetrate. In
      this study, collagen concentration and source, irradiation, and lyophilization
      conditions were varied in fabrication. Human dermal fibroblasts were seeded onto
      the composite sponge, migrated through the collagen lattice into the packet of
      DBP, and deposited a metachromatic extracellular matrix amongst the particles of
      DBP. In contrast, cells cultured in collagen sponges or in composite sponges with
      inactivated guanidine-extracted DBP did not secrete metachromatic matrix. This
      new in vitro system will be valuable in defining the mechanism of differentiation
      by osteoinductive materials and in evaluating the influence of other
      extracellular components and soluble factors on skeletal differentiation.

PMID- 8879523
TI  - Effect of composition on the gelation of tissue conditioners.
AB  - Tissue conditioners comprise poly(ethyl methacrylate) powder (or related
      copolymer) and a liquid containing a plasticizer and ethanol. Gelation times for
      two butyl/ethyl copolymers and one poly(ethyl methacrylate) polymer with buty
      phthalyl butyl glycollate or di-2-ethyl hexyl maleate and varying amounts of
      ethanol have been measured in the range 20-40 degrees C. The proprietary material
      "Viscogel" was used as a standard. Results were plotted according to the
      Arrhenius equation enabling activation energies to be determined. Values for
      activation energies ranged from 55 to 110 KJ mol-1 K-1. The 60/40 butyl/ethyl
      methacrylate copolymer gave the lowest values and those containing poly(ethyl
      methacrylate) the highest.

PMID- 8879524
TI  - Ultraviolet and fluorescence derivatization reagents for carboxylic acids
      suitable for high performance liquid chromatography: a review.
AB  - Pre- and postcolumn derivatization with a suitable chromophore or fluorophore
      have often been utilized to enhance the sensitivity and selectivity of detection
      for analytes possessing a carboxyl group. The major classes of UV and fluorescent
      derivatization reagents include the coumarin analogues, alkyl halides,
      diazoalkanes, and amines. The derivatization reaction conditions, HPLC systems
      for separation of the conjugates and detection limits of various analytes are
      presented in this review. High mass sensitivity for various carboxylic acids have
      been achieved with the hydrazides, anthracenes, and diazoalkanes.

PMID- 8879525
TI  - Determination of plasma total homocysteine and cysteine using HPLC with
      fluorescence detection and an ammonium 7-fluoro-2, 1, 3-benzoxadiazole-4
      sulphonate (SBD-F) derivatization protocol optimized for antioxidant
      concentration, derivatization reagent concentration, temperature and matrix pH.
AB  - A sensitive HPLC-fluorescence method for determining total endogenous plasma
      homocysteine (Hcy), cysteine (Cys) and cysteinylglycine (Cys-Gly) following
      derivatization with ammonium 7-fluoro 2,1,3-benzoxadiazole-4-sulphonate (SBD-F)
      is described. Quantitation utilizes an internal standard, 2-mercaptoethylamine.
      The derivatization procedure has been optimized for concentration of SBD-F,
      reducing agent (tributylphosphine) and temperature. Findings indicate that values
      for plasma determinations vary according to the nature of the matrix in which
      calibration standards are made up. If quantitation is based on a peak height
      ratio, then standards should be made up in either pH 7.4 phosphate buffered
      saline or plasma taking into account the endogenous thiol concentration. These
      findings are based on calibration data, and 30 plasma samples quantified using
      thiol standards made up in plasma, pH 7.4 and pH 9.5 buffers. By defining how
      this matrix/pH effect influences thiol quantitation, it should be possible to
      make a more meaningful comparison of Hcy measurements between laboratories. The
      chromatographic separation was investigated at several mobile-phase pH values
      with the following conditions ascertained to be optimal: a mobile phase
      consisting of 5% (v/v) acetonitrile in 0.1 M KH2PO4, pH 2.15 was run at a flow
      rate of 0.5 mL/min. It was used in conjunction with a Supelco LC-18 base
      deactivated analytical column (150 x 4.6 cm i.d. 3 microM bonded silica). The
      internal standard and thiols were measured by fluorescence detection at 385 nm
      excitation and 515 nm emmission. Plasma levels are easily measured in a 100
      microL volume. Storage for 2 months at -20 degrees C resulted in no deterioration
      of thiols. Furthermore, no difference in thiol levels was observed between bloods
      collected in lithium heparin and EDTA. Collected blood should, however, be
      separated as soon as possible to avoid red cell metabolism of Hcy which was
      observed in a case of hyperhomocysteinemia. Once derivatized, thiols are stable
      for at least one week at +4 degrees C.

PMID- 8879526
TI  - Peroxylated and hydroxylated uroporphyrins: a study of their production in vitro
      in enzymic and chemical model systems.
AB  - In previous work certain hydroxylated and peroxylated derivatives of uroporphyrin
      (URO) have been isolated from the urine of patients suffering from porphyria. We
      have now investigated the mechanism of production of these oxygenated derivatives
      of URO, using both enzymic and chemical model systems and also the effect of
      exposure to light during reoxidation of uroporphyrinogen (URO'gen). When URO'gen
      was incubated with haemolysates, peaks with the same retention times as
      peroxyacetic acid URO, meso-hydroxy URO and beta-hydroxypropionic acid URO were
      all detected. The first of these was formed in sufficient amounts to allow its
      characterization by mass spectrometry. Under these conditions, peroxyacetic acid
      derivatives of heptacarboxylate and pentacarboxylate porphyrins could also be
      produced from the corresponding porphyrinogens, but no peroxylated product could
      be obtained from coproporphyrinogen (COPRO'gen, where no acetic acid side chains
      are present) or from the fully oxidized URO. Similar results were obtained on re
      oxidation of URO'gen in the xanthine oxidase-xanthine system and in the presence
      of hydrogen peroxide/Fe-EDTA (ethylenediamine-tetraacetic acid) and here again no
      peroxylated product could be detected from either COPRO'gen or URO. Finally,
      formation of peroxyacetic acid URO could be demonstrated during photo-oxidation
      of URO'gen and this was followed by light-induced loss of both URO and its
      peroxylated derivative. It is concluded that the oxygenated derivatives arise
      from the action of reactive oxygen species on the porphyrinogens (rather than the
      porphyrins), with one of the acetic acid side chain serving as the preferential
      (or exclusive target) for peroxylation.

PMID- 8879527
TI  - Paper electrophoresis in the study of mixed ligand complexes in solution. The
      system Fe(III)- and Cr(III)-methyl cysteine-penicillamine.
AB  - A method involving use of paper electrophoresis is described for the study of
      equilibria in mixed ligand [methyl cysteine-penicillamine] complex systems in
      solution. The concentration of the primary ligand methyl cysteine was kept
      constant, while that of secondary ligand penicillamine was varied. The plots of 
      log [penicillamine] against mobility were used to obtain information on the
      formation of mixed complex and to calculate its stability constants. The binary
      equilibria M(III)-methyl cysteine have also been studied since this is a pre
      requisite for the investigation of mixed complexes. The stability constants of
      [Fe(III)- methyl cysteine-penicillamine] and [Cr(III)-methyl cysteine
      penicillamine] complexes were found to be 7.40 +/- 0.13 and 4.80 +/- 0.07 (log K
      values) for Fe(III) and Cr(III) complexes, respectively, at mu = 0.1 mol/L and at
      a temperature of 35 degrees C.

PMID- 8879528
TI  - Thin-layer chromatographic determination of catecholamines in rat plasma.
AB  - A TLC method for the quantitative determination of epinephrine, norepinephrine
      and dopamine in rat plasma is described. After deprotenization, catecholamines
      were adsorbed on acid-alumina and acetylated. The acetyl derivatives were
      extracted using a C18 minicolumn, resolved on HPTLC plates and quantitated by
      fluorescence densitometry at 415 nm, using isoprenaline as internal standard.

PMID- 8879529
TI  - Purification of trypsin by affinity chromatography with sulphamethoxazolum
      ligand.
AB  - Pharmaceuticals have already been studied comprehensively both in their physico
      chemical properties and their biological effect. Most of these compounds are
      chemically synthesized and less susceptible to degradation by micro-organism or
      suffering from solvent effect compared with the bio-active substances. Affinity
      chromatographic columns composed of pharmaceutical compounds as the ligand should
      have advantages such as long life, low cost and low toxicity. This paper
      describes the preparation of sulphamethoxazolum immobilized on silica as the
      column packing and the study of its interactions with proteins and enzymes. It
      was found that this material showed an affinity specific to trypsin with a
      dissociation constant of around 10(-6) M. The enzymatic activity of commercial
      trypsin can be increased by a factor of ten after purification with such a
      column.

PMID- 8879530
TI  - TLC characterization of small unilamellar liposomes containing D-myo-inositol
      derivatives.
AB  - The thin-layer chromatographic (TLC) behaviour of small unilamellar liposomes
      containing inositol phosphates (IPs) was studied. The vesicles contained
      different concentrations of D-myo-inositol 1,4,5-triphosphate (IP3), D-myo
      inositol 1,2,6-triphosphate (alpha-trinositol, PP 56, a novel Perstorp Pharma
      derivative), D-myo-inositol 1,3,4,5-tetraphosphate (IP4), D-myo-inositol
      1,3,4,5,6-pentakisphosphate (IP5) and D-myo-inositol 1,2,3,4,5,6-hexakisphosphate
      (IP6). Migration of all liposome batches was compared to that of control
      liposomes (multilamellar and small unilamellar, both containing only triple
      distilled water), and to that of free phosphatidylcholine (PC). The same amount
      of lipid was used in all situations. Thin-layer chromatography was performed with
      silica gel as adsorbent. The developing solvent was an n-buthanol:ethanol:water
      mixture in a 4:3:3 volume ratio. At doses higher than 10(-2) M liposomes
      containing alpha-trinositol and IP6 had a different migration than PC, MLV or SUV
      as well as all batches of liposomes. Physiological studies (using as model
      endothelized rat aorta rings) proved that in this situation they had no effects.

PMID- 8879531
TI  - HPLC determination of captopril in human plasma and its pharmacokinetic study.
AB  - A simple and sensitive reversed-phase liquid chromatographic method has been
      developed and validated for the analysis of captopril in human plasma and the
      study of the pharmacokinetics of the drug in human body. Captopril was stabilized
      by forming an adduct with p-bromophenacyl bromide. The adduct formed and 4-chloro
      2-nitroaniline (internal standard) were extracted with ethyl acetate:benzene
      (1:1), and then measured by HPLC using a Spherisorb C18 column as stationary
      phase and a water:acetonitrile:acetic acid mixture (44:55:0.2, v/v/v) as mobile
      phase. Captopril was quantified by absorbance at 258 nm. The method proved to be
      linear in the clinical range of 5-500 ng/mL. The lower limit of detection of
      captopril in plasma was 2 ng/mL. Intra-day and inter-day coefficients of
      variation of assay for captopril in plasma were 5.8%-8.5% (n = 7) and 8.0%-9.5%
      (n = 5), respectively. The recoveries of captopril were 90%-98% for plasma. The
      data obtained was fitted with 3P87 program on computer to study the
      pharmacokinetics. The results showed that the disposition of captopril was
      conformed to a two-compartment open model with Tmax = 0.56 h, Cmax = 266.5 ng/mL
      and AUC(zero)-infinity = 380.3 ng.h/mL. The method has been used to determine
      captopril in plasma samples from ten volunteers and provided data on the
      pharmacokinetics of the drug. The results inferred that captopril is absorbed
      rapidly and had a relatively short half-life time in healthy individuals.

PMID- 8879532
TI  - High-speed analysis of catecholamines in plasma by medium-pressure mu-LC with an
      amperometric detector.
AB  - A high-speed highly sensitive and reproducible method for the determination of
      catecholamines in small plasma volumes has been developed. Catecholamines were
      separated on a short capillary fused-silica column (0.32 mm i.d.) packed with a
      reverse-phase sorbent with a particle size of 10 microns. The time of a single
      chromatographic analysis was less than 6 min, and the operating pressure in the
      system was not higher than 5.0 MPa. The required volume of blood plasma was 0.5
      mL. When a 10 microL sample previously concentrated on alumina was injected into
      the column, the limits of amperometric detection for noradrenaline (NA),
      adrenaline (A), 3,4-dihydroxy-benzylamine (DHBA), and dopamine (DA) were 3.9,
      2.6, 1.8 and 5.6 ng/L, respectively. The average variation coefficient was 17.4%.

PMID- 8879533
TI  - Replacement of chloroform throughout glycosphingolipid isolation.
AB  - Chloroform, the predominant constituent of solvents used for lipid extraction and
      chromatography, is believed to give rise to birth defects and serious damage to
      health, and may also be carcinogenic. Therefore, simple and successful methods
      have been developed to replace chloroform throughout the isolation of
      glycosphingolipids (GSLs) by less harmful solvents. Gangliosides of sheep brain
      (ganglio-series gangliosides GM1, GDla, GD1b and GT1b) and of lymphocyte-derived
      mouse hybridoma cells (namely GM3) were extracted with six different solvent
      mixtures. Chloroform:methanol:water (40:80:30, v/v/v) was employed as reference
      (solvent I). Combinations without chloroform were: n-propanol:water (40:10, v/v)
      (II), methylisobutylketone:methanol:water (40:80:30, v/v/v) (III),
      ethylacetate:methanol:water (40:72:28, v/v/v) (IV), methylacetate:methanol:water
      (40:72:28, v/v/v) (V) and petroleum ether:isopropanol:water (40:112:38, v/v/v)
      (VI). After extraction and dialysis, the weight of lipid extract as well as the
      content of sialic acid, gangliosides, sulphatides and phospholipids were
      determined. Quantitation of GSL yields in crude extracts obtained by the
      alternative solvent mixtures II to VI showed recoveries of brain gangliosides
      from nearly 67% up to 104% compared with the reference solvent I. Extraction of
      hybridoma cells by means of the alternative combinations without chloroform
      revealed at least the same and mostly better ganglioside yields in the range from
      98% to 116% with regard to the reference solvent I. n-Propanol:water (II) and
      methylisobutylketone:methanol:water (III) were the recommended extractants for
      both tissues. Therefore, the methods described offer simple, less hazardous and
      successful strategies for GSL extraction in excellent yield without the need for
      using chloroform.

PMID- 8879534
TI  - Effect of mobile phase composition on selectivity in preparative hydrophobic
      interaction chromatographic purification of glucagon.
AB  - A weakly hydrophobic acrylester copolymer, Amberlite XAD-7, has been used in the
      purification process of glucagon production for elimination of protein impurities
      in the crude glucagon fractions, obtained from the industrial waste from insulin
      production. Varying the mobile phases composition, it was shown that suitable
      selectivity for the separation of proteins under non-denaturing conditions can be
      achieved. The purified glucagon, obtained at the proposed chromatographic
      conditions has a biological activity of above 1 IU/mg.

PMID- 8879535
TI  - Comparison of high performance capillary electrophoresis and liquid
      chromatography for the determination of acyclovir and guanine in pharmaceuticals
      and urine.
AB  - High-performance capillary electrophoresis (HPCE) and high-performance liquid
      chromatography (HPLC) were developed and applied to the determination of
      acyclovir (ACV) and guanine (G) in pharmaceuticals. The comparison study showed
      that two methods gave comparable results in linear range, recovery and
      reproducibility. HPCE was used for the determination of ACV and G in urine; the
      recovery was better than 81.3% and the RSD was less than 4.4%.

PMID- 8879536
TI  - Separation and identification of some cephalosporins on impregnated TLC plates.
AB  - Ethylenediamine tetra-acetic acid disodium salt dihydrate was used as an
      impregnating reagent to resolve some cephalosporins. Both changes in the
      concentration of the impregnating reagent and in the composition of the mobile
      phase influenced the resolution. Three new solvent systems (I) propionic acid:2
      propanol:water (6:3:3, v/v/v), (II) 2-prapanol:water:ethyl acetate (5:3:3, v/v/v)
      and (III) n-butanol:water:acetic acid (5:4:2, v/v/v) were found to be successful.

PMID- 8879537
TI  - A highly practical synthesis of the sialyl Lewis X pentasaccharide and an
      investigation of binding to E-, P-, and L-selectins.
AB  - A practical synthesis of the sialyl Lewis X (sLex) pentasaccharide, NeuAc alpha 2
      3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta OEt (1), as a potential
      blocker for E-selectin has been described. The glycosylation of a trisaccharide
      acceptor, Fuc alpha (1-3)GlcNAc beta (1-3)Gal beta OEt, with a disaccharide
      donor, NeuAc alpha (2-3)Gal beta SMe, did not yield the desired sLex
      pentasaccharide 1 at all. However, the glycosylation of a disaccharide acceptor,
      GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal
      beta SMe, quantitatively yielded the tetrasaccharide NeuAc alpha (2-3)Gal beta (1
      4)GlcNAc beta (1-3)Gal beta OEt. This tetrasaccharide is readily converted to the
      title compound in a high yield by fucosylation, followed by deprotection. The
      inhibitory activities of compound 1 toward the binding of the natural ligand
      (sLex) with the E-, P-, and L-selectins were stronger than those of the sLex
      tetrasaccharide.

PMID- 8879538
TI  - Synthesis and pharmacology of alkanediguanidinium compounds that block the
      neuronal nicotinic acetylcholine receptor.
AB  - Taking as models the polyamine toxin fraction FTX from the funnel-web spider
      venom, and the guanidinium moiety of guanethidine, a series of azaalkane-1, omega
      diguanidinium salts were obtained. Some of them blocked ion fluxes through the
      neuronal nicotinic receptors for acetylcholine (nAChR). The blockade was exerted
      at submicromolar concentrations, suggesting a highly selective interaction with
      the nAChR. In fact, the active compounds on the nAChR ion channel did not
      recognize the voltage-dependent Na+ or Ca2+ channels of bovine adrenal chromaffin
      cells. Therefore, these compounds may be useful tools to clarify the functions of
      nAChR receptors in the central and peripheral nervous systems.

PMID- 8879539
TI  - Salen-anthraquinone conjugates. Synthesis, DNA-binding and cleaving properties,
      effects on topoisomerases and cytotoxicity.
AB  - A series of amidoethylamino-anthraquinone derivatives bearing either one or two
      salen (bis(salicylidene)ethylenediamine) moieties complexed with CuII or NiII
      have been synthesized, and their DNA-binding and cleaving properties examined.
      The effects of the mono- and di-substituted anthracenedione-salen conjugates on
      DNA cleavage mediated by topoisomerases I and II have also been determined, as
      well as their cytotoxicity toward human KB cells. The anthraquinone-salen. NiII
      conjugates bind to GC-rich sequences in DNA, but do not cleave the macromolecule.
      By contrast, the anthraquinone-salen. CuII hybrids do not recognize particular
      nucleotide sequences but efficiently induce single-strand breaks in DNA after
      activation. The 5,8-dihydroxy-anthraquinone conjugates are more cytotoxic and
      more potent toward topoisomerase II than the non-hydroxylated analogues, but they
      are less cytotoxic than the salen-free anthraquinones. The attachment of a salen.
      CuII complex to the anthraquinone chromophore can confer DNA cleaving properties
      in vitro, but this is at the expense of cytotoxic activity. Anthraquinone-salen.
      CuII complexes may find useful employ as footprinting probes for investigating
      ligand-DNA interactions.

PMID- 8879540
TI  - Properties of diacetyl (acetoin) reductase from Bacillus stearothermophilus.
AB  - The cells of Bacillus stearothermophilus contain an NADH-dependent diacetyl
      (acetoin) reductase. The enzyme was easily purified to homogeneity, partially
      characterised, and found to be composed of two subunits with the same molecular
      weight. In the presence of NADH, it catalyses the stereospecific reduction of
      diacetyl first to (3S)-acetoin and then to (2S,3S)-butanediol; in the presence of
      NAD+, it catalyses the oxidation of (2S,3S)- and meso-butanediol, respectively,
      to (3S)-acetoin and to (3R)-acetoin, but is unable to oxidise these compounds to
      diacetyl. The enzyme is also able to catalyse redox reactions involving some endo
      bicyclic octen- and heptenols and the related ketones, and its use is suggested
      also for the recycling of NAD+ and NADH in enzymatic redox reactions useful in
      organic syntheses.

PMID- 8879541
TI  - Tyrphostins IV--highly potent inhibitors of EGF receptor kinase. Structure
      activity relationship study of 4-anilidoquinazolines.
AB  - Potent 4-anilido-substituted quinazolines which potently inhibit epidermal growth
      factor receptor (EGFR) kinase were prepared. Structure-activity relationship
      studies reveal high sensitivity to substitution at the aniline ring.

PMID- 8879542
TI  - Synthesis of 4,17-diazasteroid inhibitors of human 5 alpha-reductase.
AB  - The synthesis of the 17-aza isomer of finasteride is described. With the side
      chain amide group of the compound existing in the Z configuration the structure
      is similar to one of the two favored conformations of finasteride. A series of
      4,17-diazasteroids was assayed against the isoenzymes of human 5 alpha-reductase.

PMID- 8879543
TI  - Synthesis and properties of alpha- and beta-oligodeoxynucleotides containing
      alpha- and beta-1-(2-O-methyl-D-arabino-furanosyl)thymine.
AB  - Synthesis of the alpha- and beta-anomer of 2'-OMe-araT (alpha- and beta-1-(2-O
      methyl-D-arabinofuranosyl)thymine) and their incorporation into
      oligodeoxynucleotide (ODN) analogues is described. Condensation of the key
      arabinofuranose derivative with silylated thymine afforded the alpha-anomer and
      the beta-anomer which were converted into the respective phosphoramidite building
      blocks. Automated synthesis of beta-ODNs containing beta-2'-OMe-araT (by use of
      standard beta-amidites and phosphoramidite building block 9b) and alpha-ODNs
      containing alpha-2'-OMe-araT (by use of alpha-T-amidite and phosphoramidite
      building block 9a) allowed evaluation of their properties. With regard to 3'
      exonucleolytic degradation, 3'-end incorporation of either beta- or alpha-2'-OMe
      araT resulted in considerable stabilization compared to unmodified beta-ODNs.
      Thermal stabilities of duplexes formed between modified ODNs and both unmodified
      DNA and RNA were evaluated and compared to unmodified controls. In all
      experiments stable duplexes were formed, but whereas beta-ODNs containing beta-2'
      OMe-araT showed moderately lowered thermal stabilities towards both DNA and RNA,
      alpha-ODNs containing alpha-2'-OMe-araT exhibited significantly increased melting
      points (compared to beta-ODN controls) when complexed with RNA. These results
      illustrate the potential of using arabino-configurated nucleosides as modified
      monomers in biologically active ODN-analogues, either as, e.g., 2'-O-alkylated or
      2'-O-functionalized derivatives.

PMID- 8879544
TI  - A new family of potential oncostatics: 2-chloroethylnitrososulfamides (CENS)--I.
      Synthesis, structure, and pharmacological evaluation (preliminary results).
AB  - A new series of alkylating agents, 2-chloroethylnitrososulfamides (CENS), were
      developed on the model of 2-chloroethylnitrosoureas. Starting from chlorosulfonyl
      isocyanate, a four-step synthesis (carbamoylation-sulfamoylation, Mitsunobu
      alkylation, deprotection, and nitrosation) gives the title compounds in a 47-58%
      overall yield. The selection of the nitrosation site can be directed through an
      alternative route. The pharmacological evaluation shows a significant oncostatic
      activity towards both A549 and MCF7 cell lines.

PMID- 8879545
TI  - A protein radical cage slows photolysis of methylcobalamin in methionine synthase
      from Escherichia coli.
AB  - Methionine synthase from Escherichia coli is a B12-dependent enzyme that utilizes
      a methylcobalamin prosthetic group. In the catalytic cycle, the methyl group of
      methylcobalamin is transferred to homocysteine, generating methionine and cob(I)
      alamin, and cob(I)alamin is then remethylated by a methyl group from
      methyltetrahydrofolate. Methionine synthase occasionally undergoes side reactions
      that produce the inactive cob(II)alamin form of the enzyme. One such reaction is
      photolytic homolysis of the methylcobalamin C-Co bond. Binding to the methionine
      synthase apoenzyme protects the methylcobalamin cofactor against photolysis,
      decreasing the rate of this reaction by approximately 50-fold. The X-ray
      structure of the cobalamin-binding region of methionine synthase suggests how the
      protein might protect the methylcobalamin cofactor in the resting enzyme. In
      particular, the upper face (methyl or beta face) of the cobalamin cofactor is in
      contact with several hydrophobic residues provided by an alpha-helical domain,
      and these residues could slow photolysis by caging the methyl radical and
      favoring recombination of the CH3./cob(II)alamin radical pair. We have introduced
      mutations at three positions in the cap domain; phenylalanine 708, phenylalanine
      714, and leucine 715 have each been replaced by alanine. Calculations based on
      the wild-type structure predict that two of these three mutations (Phe708Ala and
      Leu715Ala) will increase solvent accessibility to the methylcobalamin cofactor,
      and in fact these mutations result in dramatic increases in the rate of
      photolysis. The third mutation, Phe714Ala, is not predicted to increase the
      accessibility of the cofactor and has only a modest effect on the photolysis rate
      of the enzyme. These results confirm that the alpha-helical domain covers the
      cofactor in the resting methylcobalamin enzyme and that residues from this domain
      can protect the enzyme against photolysis. Further, we show that binding the
      substrate methyltetrahydrofolate to the wild-type enzyme results in a saturable
      increase in the rate of photolysis, suggesting that substrate binding induces a
      conformational change in the protein that increases the accessibility of the
      methylcobalamin cofactor.

PMID- 8879546
TI  - Charge is the major discriminating factor for glutathione reductase versus
      trypanothione reductase inhibitors.
AB  - Benson et al. (Biochem. J. 1992, 286, 9) reported three novel competitive
      inhibitors of trypanothione reductase (TR), which were selected to complement a
      hydrophobic region identified on the TR structure which was not present on human
      glutathione reductase (hGR). Benson et al. also noted that chlorpromazine, a
      tricyclic antidepressant known to have trypanocidal activity, was an inhibitor of
      TR. Here we show that chlorpromazine is a competitive inhibitor of TRs from
      Crithidia fasciculata (Ki = 14 microM) and Trypanosoma cruzi (Ki = 10 microM),
      but the drug binds > 50-fold more weakly (Ki = 762 microM) to hGR. Analogues of
      chlorpromazine differing in the length of the side chain carrying the positively
      charged R-group are also selective TR inhibitors whereas, a tricyclic structure
      carrying a negatively charged side chain is a competitive inhibitor with
      selectivity for hGR (K(hGR)i = 165 microM vs. K(TR)i = 1400 microM). This finding
      suggests that simple charge characteristics, rather than differences in
      hydrophobicity, may account for a significant portion of the selectivity of this
      series of inhibitors for these two enzymes. Electrostatic analysis of the
      structures of TR and hGR thus provides a rationale for these results, and offers
      a new principle for inhibitor design. The principle gains further support from
      the observation that all known tricyclic competitive inhibitors of TR are
      positively charged. In order to investigate the in vivo relevance of our findings
      we have examined the effect of chlorpromazine and its negatively charged analogue
      on the growth of C. fasciculata parasites. Consistent with our kinetics,
      chlorpromazine (50 microM) inhibited the growth of parasites by 50%, while no
      measurable decrease in parasite growth rate was noted in the presence of the
      negatively charged inhibitor (400 microM). Furthermore, the highly similar
      inhibitory profiles of C. fasciculata TR and T. cruzi TR suggest that drug-design
      studies using the structurally better-studied C. fasciculata TR are also relevant
      to the human pathogen T. cruzi.

PMID- 8879547
TI  - Molecular structure and dynamics of some potent 5-HT3 receptor antagonists.
      Insight into the interaction with the receptor.
AB  - The molecular structure and the dynamic behaviour of some potent 5-HT3
      antagonists structurally related to quipazine have been investigated by NMR
      spectroscopy and by computational methods in order to gain insight into the
      structure-activity relationships at a molecular level. The role of the different
      dynamic behaviour of these compounds in the binding to 5-HT3 receptors is
      discussed. A model of ligand-receptor interaction has been developed on the basis
      of molecular orbital calculations and on the reference ligands quipazine,
      ondansetron and LY278584. The interaction model proposed herein rationalizes the
      observed agonist-antagonist shift between quipazine and investigated compounds
      with the assumption of different but overlapping binding domains for antagonists
      and agonists at the 5-HT3 receptor.

PMID- 8879548
TI  - cis-gigantrionenin and 4-acetyl gigantetrocin A, two new bioactive annonaceous
      acetogenins from Goniothalamus giganteus, and the stereochemistries of acetogenin
      1,2,5-triols.
AB  - Using activity-directed fractionation, two new bioactive acetogenins, cis
      gigantrionenin (1) and 4-acetyl gigantetrocin A (2), have been isolated from the
      bark of Goniothalamus giganteus (Annonaceae). Compound 1 has a cis-mono-THF ring
      with one flanking hydroxyl and possesses a cis-double bond at C-21/22 of the
      aliphatic chain; it represents only the second example of the cis-mono-THF ring
      annonaceous acetogenins having one flanking hydroxyl. Compound 2 has a trans-mono
      THF ring with one flanking hydroxyl, but it possesses a mono-acetyl group at the
      4-OH position; it represents only the second natural example of the acetylated
      annonaceous acetogenins; the first acetogenin reported, uvaricin, was mono
      acetylated at the 24-OH. The stereochemistries of 1 and 2 were determined by the
      advanced Mosher ester method. In addition, the absolute stereochemistries of
      gigantriocin (3), gigantrionenin (4), and giganenin (5) were determined by the
      advanced Mosher ester method and by circular dichroism (CD). The
      stereochemistries of the 7,8-diols in murihexocins A (6) and B (7) were
      determined to have the S,S-configurations, respectively.

PMID- 8879549
TI  - Applying Mosher's method to acetogenins bearing vicinal diols. The absolute
      configurations of muricatetrocin C and rollidecins A and B, new bioactive
      acetogenins from Rollinia mucosa.
AB  - Muricatetrocin C (1), rollidecin A (2), and rollidecin B (3), three new bioactive
      annonaceous acetogenins bearing vicinal diols, were isolated from the leaves of
      Rollinia mucosa (Annonaceae) using activity-directed fractionation. The total
      structural elucidations of 1-3, including the absolute stereochemistries of the
      vicinal diols, were achieved by analyzing their per-Mosher ester derivatives. All
      three compounds showed potent and selective inhibitory effects against several
      human cancer cell lines.

PMID- 8879550
TI  - 3-Amino-2-hydroxy-propionaldehyde and 3-amino-1-hydroxy-propan-2-one derivatives:
      new classes of aminopeptidase inhibitors.
AB  - 3-Amino-2-hydroxy-propionaldehydes [H2NCH(R)CHOHCHO with R = H, i-Bu, CH2Ph] were
      designed as metallo-aminopeptidase inhibitors based on the metal active site
      chelation concept. These compounds were found to be micromolar inhibitors of
      aminopeptidase-M (AP-M, EC 3.4.11.2) with potencies similar to bestatin (Ki = 3.5
      microM). Notably, compound 5a (R = H) is a selective inhibitor of AP-M (Ki = 7
      microM) with respect to cytosolic leucine aminopeptidase (LAPc, EC 3.4.11.1) (Ki
      = 385 microM). However, due to their easy oligomerization, these compounds are
      low practical value. In contrast, the corresponding isomeric 3-amino-1-hydroxy
      propan-2-one derivatives [H2NCH(R)COCH2OH with R = H, i-Bu, CH2Ph, i-Pr, CH2Biph]
      are well defined structures. These hydroxymethylketones also exhibit micromolar
      affinities on AP-M. Compound 6c (R = CH2Ph) was the most potent (Ki = 1 microM).
      Selectivity studies of 6a (R = H) and 6b (R=i-Bu) show a preference for AP-M.
      Compound 6a is moderately active on AP-M (Ki = 25 microM) and inactive on LAPc.
      This new class of inhibitors is proposed to bind as bidentates, analogous to
      hydroxamates.

PMID- 8879551
TI  - Synthesis of bis-gamma-butyrolactones containing conformationally constrained (S)
      and (R)-diacylglycerol structures.
AB  - The synthesis of two sets of rigid diacylglycerol (DAG) analogues with either the
      (S)-DAG or (R)-DAG enantiomer embedded into a bis-gamma-butyrolactone template
      was accomplished stereoselectively from di-O-isopropylidene-alpha-D-apiose. The
      key step in both syntheses was the assemblage of the bicyclic perhydrofuro[3,4
      b]furan ring system via a radical exo-dig intramolecular cyclization. A
      lipophilic undecanyl alkyl chain attached at C-3 of the fully assembled
      perhydrofuro[3,4-b]furan-2,4-dione (bis-gamma-butyrolactone) template can adopt
      two orientations with the one directed away from the concave face of the bicyclic
      system favored by a 4 to 1 ratio in each case. Evaluation of the final target
      pairs of enantiomers as PK-C alpha ligands revealed that the template containing
      an embedded (R)-DAG structure was more effective. The difference in binding
      affinity was also modulated by the direction of the alkyl chain.

PMID- 8879552
TI  - The synthesis and in vitro antibacterial activity of conformationally restricted
      quinolone antibacterial agents.
AB  - Two series of conformationally restricted quinolone antibacterials were
      synthesized. One series was restricted by formation of a tetrahydrofuran ring
      between the C-6 position and the C-7 position of the quinolone ring skeleton. The
      second series achieved conformational rigidity by formation of a tetrahydrofuran
      ring between the C-7 and the C-8 positions. These compounds were evaluated for
      their in vitro antibacterial activity. Compounds 19 and 20 were the most active
      compounds in either series and were about equipotent.

PMID- 8879553
TI  - SRS-A antagonist pyranoquinolone alkaloids from east African Fagara plants and
      their synthesis.
AB  - Three pyranoquinolone alkaloids isolated from two East African Fagara plants have
      been found to exhibit SRS-A antagonist action. Their synthesis has been
      accomplished, using a modified Coppola's method or a thermal cyclization followed
      by an electrocyclic ring closure.

PMID- 8879554
TI  - The high affinity melationin binding site probed with conformationally restricted
      ligand--I. Pharmacophore and minireceptor models.
AB  - The affinities of enantiomers of conformationally restricted melatonin analogues
      for the ML-1 and ML-2 putative melatonin receptor subtypes are reported. Most
      ligands exhibited reversed stereoselectivity when competing with 125I 2
      iodomelatonin binding to chicken retinal (ML-1) and hamster brain (ML-2)
      membranes, further supporting the biochemical and pharmacological differences
      reported for these two sites. Based on the data for the ML-1 site and thorough
      conformational analyses of several ligands, two pharmacophore models were derived
      using the program APOLLO. The pharmacophoric elements included were putative
      receptor points from the amide NH, the amide CO, and the methoxy-O, together with
      the normal through the phenyl ring. The large drop in ML-1 affinity observed for
      4-methoxy-2-acetamido-indan (6a) could not be explained from either of these
      models. Minireceptors were subsequently built around the two pharmacophores using
      Yak. Analysis of the resulting ligand-minireceptor interactions offered an
      explanation for the low affinity of 6a and allowed one of the pharmacophore
      models to be selected for use in future drug design.

PMID- 8879555
TI  - The high affinity melatonin binding site probed with conformationally restricted
      ligands--II. Homology modeling of the receptor.
AB  - We present the first 3-D model of the melatonin receptor based on the recently
      published amino acid sequence of the cloned melatonin receptor. The seven trans
      membrane helices were positioned using the helices found in the structure of
      Bacterio Rhodopsine. From the results of an indirect modeling study with six
      melatonergic agents, an alignment of these compounds was found directing towards
      common interaction points. These points are suggested to be the two serines in
      helix three and the histidine in helix five, forming hydrogen bonds with the
      amide function and the methoxy-oxygen in melatonin, respectively. The ligands
      were docked into these binding sites and the receptor-ligand complexes were
      energy minimized. Considering the position of the active and inactive ligands in
      the receptor and their respective occupied volumes, the structure-activity
      relationships are rationalized by the suggested model. This model can be of use
      as a pharmacological test model in molecular biological studies and as a basis to
      develop compounds being active as synchronizing circadian agents.

PMID- 8879556
TI  - A cyclic phosphonamidate analogue of glucose as a selective inhibitor of
      inverting glycosidases.
AB  - Recent work in the synthesis of cyclic phosphonate analogues of glucose [Darrow,
      J.W.; Drueckhammer, D.G. (1994) J. Org. Chem. 1994, 59, 2976] has been extended
      to the synthesis of a corresponding phosphonamidate analogue. A phosphonate salt,
      phosphonate methyl ester, and phosphonamidate analogue were tested as inhibitors
      of two inverting alpha-glycosidases, (trehalase and glucoamylase), and two
      retaining glycosidases, (alpha-glucosidase and beta-glucosidase). No inhibition
      of any of these enzymes was observed with the phosphonate salt or methyl ester.
      However, the phosphonamidate gave moderate competitive inhibition of the two
      inverting glycosidases and the retaining alpha-glucosidase but no inhibition of
      beta-glucosidase. The phosphonamidate showed enhanced binding relative to a
      simple monosaccharide only with the inverting glycosidases. This enhanced binding
      is believed to be due to hydrogen bonding interactions between the
      phosphonamidate group and two active site carboxylate residues implicated in
      catalysis. The selectivity toward inverting glycosidases is consistent with
      differences in distance of an active site carboxylate from the anomeric carbon of
      the glycoside substrate for the inverting versus the retaining glycosidases.

PMID- 8879557
TI  - Synthesis and inhibitory properties of a thiomethylmercuric sialic acid with
      application to the X-ray structure determination of 9-O-acetylsialic acid
      esterase from influenza C virus.
AB  - 2-alpha-Thiomethylmercuryl 9-acetamido-9-deoxy-sialoside was prepared and found
      to inhibit the 9-O-acetylsialic acid esterase from influenza C virus in a
      competitive manner with a Ki of 4.2 +/- 0.5 mM. The inhibitor is being used in
      the X-ray determination of the crystal structure of the esterase.

PMID- 8879558
TI  - Cytotoxic trichilin-type limonoids from Melia azedarach.
AB  - Five new trichilin-type limonoids, named 12-deacetyltrichilin I (1), 1
      acetyltrichilin H (2), 3-deacetyltrichilin H (3), 1-acetyl-3-deacetyltrichilin H
      (4), 1-acetyl-2-deacetyltrichilin H (5), together with four known trichilins,
      meliatoxin B1 (6), trichilin H (7), trichilin D (8) and 1,12-diacetyltrichilin B
      (9) were isolated from the extract of the root bark of Melia azedarach. The
      structures were elucidated by spectroscopic means and their cytotoxic activities
      against P388 cells in vitro were tested by means of MTT assay.

PMID- 8879559
TI  - Synthesis and biological evaluation of an electronically activated isooxacephem.
AB  - New isooxacephem (+/-)-3-ethyl 2-hydrogen (6RS,7RS)-8-oxo-7-(phenylacetamido)-4
      oxa-1-azabicyclo [4.2.0]oct-2-ene-2, 3-dicarboxylate (8) was synthesized from (+/
      )-dibenzyl 2-[cis-2-oxo-3-(phenylacetamido)-4-styryl-1-azetidinyl]-2-[t-
      butyldimethylsiloxy(methoxycarbonyl)methyl]malonate (1) in six steps. This
      bicyclic beta-lactam was found to possess notable biological activities against
      several pathogenic microorganisms in vitro, including Staphylococcus aureus 95,
      S. aureus FDA 209P, Escherichia coli ATCC 39188, Salmonella typhi O-901,
      Pseudomonas aeruginosa 18S-H, P. aeruginosa 1101-75, and Klebsiella pneumoniae
      NCTC 418. The electronic activation of the beta-lactam moiety by an ester group
      plays a prominent role in the biological activity of this novel isooxacephem.

PMID- 8879560
TI  - Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA--II.
      Modification of pyrrolidine ring at P1' proline.
AB  - Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1'
      proline was carried out. Compound 26, which has a Cl atom in the 4(S)-position
      was the most active among inhibitors substituted with other halogen atoms or
      other substituents. Furthermore, the replacement of the Z group in compound 26
      with five- or six-membered fused aromatic heterocycle carbonyl groups produced
      more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the
      best of these and showed Ki = 4.5 nM against HIV PR and IC90S 0.58 microM and
      0.06 microM in chronic and acute infections, respectively. These results suggest
      that the combination of the 4(S)-CI atom and fused bicyclic heterocycles may be
      effective in improving their cellular penetration.

PMID- 8879561
TI  - Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole
      analogues of duocarmycin B2.
AB  - A series of the eight-substituted A-ring pyrrole derivatives of duocarmycin B2
      were synthesized, and evaluated for in vitro anticellular activity against HeLa
      S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In
      addition, the stability of the analogues in aqueous solution was examined. The 8
      H and the 8-CN compounds which cannot structurally release the cyclopropane
      compound (DU-86), exhibited extremely diminished anticellular activity compared
      with duocarmycin A (1a) or DU-86. The ethers and the sulfonates which were not
      converted to DU-86 under usual conditions (35 degrees C, pH 7), showed almost
      equal in vivo activities to that of 1a. However, their optimal doses were
      significantly higher than that for 1a. Most of the A-ring pyrrole analogues which
      can be chemically or enzymatically converted to DU-86, displayed remarkably
      superior in vivo antitumor activity to 1a. These results suggest that the A-ring
      pyrrole analogues need to chemically or enzymatically release DU-86 as an active
      metabolite to exhibit potent in vivo antitumor activity.

PMID- 8879562
TI  - Elimination of sequence ambiguities by a single-step modification of a solid
      phase, single-stranded sequencing protocol.

PMID- 8879563
TI  - Recovery of unlabeled PCR product from polyacrylamide gel for sequencing.

PMID- 8879564
TI  - PCR-RFLP genotyping of murine MHC haplotypes.

PMID- 8879565
TI  - Cautionary note on the use of dUMP-containing PCR primers with Pfu and VentR DNA
      polymerases.

PMID- 8879566
TI  - Use of the fluorescent dye PicoGreen for quantification of PCR products after
      agarose gel electrophoresis.

PMID- 8879567
TI  - Quantitation of T-cell receptor transcripts using a wet agarose gel method.

PMID- 8879568
TI  - Simple method for constructing internal standards for competitive PCR.

PMID- 8879569
TI  - Limited growth PCR screening of a plasmid library.

PMID- 8879570
TI  - Streamlined procedures for screening a P1 library.

PMID- 8879571
TI  - Hydrogen peroxide decomposes the heme compound in forensic specimens and improves
      the efficiency of PCR.

PMID- 8879572
TI  - Isolation of multiple mRNAs from a few eukaryotic cells: a fast method to obtain
      templates for RT-PCR.

PMID- 8879573
TI  - Improved dicistronic mRNA expression vectors for efficient selection of
      transfectants highly expressing foreign genes.

PMID- 8879574
TI  - Method for rapid restriction analysis of YAC clones.

PMID- 8879575
TI  - Differential display without radioactivity--a modified procedure.

PMID- 8879576
TI  - Method for joining DNA fragments using positive selection.

PMID- 8879577
TI  - Removal of template after random priming yields DNA probes of maximal specific
      activity.

PMID- 8879578
TI  - Repeated probing of western blots obtained from coomassie brilliant blue-stained
      or unstained polyacrylamide gels.

PMID- 8879579
TI  - Use of 33P for ribozyme assays: the safe way.

PMID- 8879580
TI  - RNA from air-dried frozen sections for RT-PCR and differential display.

PMID- 8879581
TI  - Use of the two-hybrid system and random sonicated DNA to identify the interaction
      domain of a protein.

PMID- 8879582
TI  - Molecular biology databases on the Internet.

PMID- 8879583
TI  - Simple strategy for sequencing cDNA clones.
AB  - We describe a simple method for constructing subclones containing overlapping
      nested deletions from cDNA clones (both lambda phage clones and plasmid clones).
      A PCR-amplified insert is partially digested with 4-cutter restriction enzyme(s).
      Complete digestion of this DNA with two restriction enzymes, having unique
      cutting sites at one or the other end of the amplified DNA, creates two sets of
      overlapping nested subfragments. When recloned into each of two doubly cut
      pBluescript plasmid vectors, only the two sets of nested subfragments are
      produced. Minimal nested sets can be constructed by screening subclones using
      colony PCR, and this set can then be used to determine the entire sequence of the
      cDNA clone. This method requires only a single cloning step and can be generated
      from an insert that is amplified directly from a lambda phage clone. This
      procedure eliminates the sequencing redundancy problem inherent in shotgun
      cloning, allows large clones to be sequenced using universal primers only and is
      well-suited for automated DNA-sequencing. Using this method, we successfully
      sequenced five cDNA clones of five Drosophila subobscura genes.

PMID- 8879584
TI  - Automated DNA sequencing requiring no DNA template purification.
AB  - A critical component in automated fluorescent DNA sequencing is good quality of
      DNA template. In an effort to reduce the dependence of sequencing success on DNA
      template quality, the effect of heat-soaked PCR on automated sequencing reactions
      has been examined. We have found that the heat-soaked PCR protocol considerably
      improves the overall quality of sequence data and significantly reduces the
      dependence on the quality of DNA templates. The improvement is corroborated by
      our ability to obtain over 500 bp of readable sequence per reaction using DNA
      from E. coli lysates as template obviating DNA purification.

PMID- 8879585
TI  - Isolation of high-molecular-length DNA from human skin.
AB  - An agarose plug method for isolating high-molecular-length DNA from mammalian
      tissues has been developed, including from those that are difficult, such as
      skin. It gives high yields of DNA that contain a minimum of single-strand breaks
      and is readily digested by restriction and other nucleases. The method requires
      only simple equipment and is readily adaptable to field or clinical studies.

PMID- 8879587
TI  - Efficient long-PCR site-specific mutagenesis of a high GC template.
AB  - A long PCR method was developed for the efficient site-specific mutagenesis of
      herpes simplex virus (HSV-1) DNA fragments with high GC content. In this
      protocol, a PCR product was partially extended first using a cloned DNA fragment.
      The final mutagenized fragment was produced after a second extension using
      another PCR product and final amplification using external primers. The
      sequential use of two extension reactions increased the predicted frequency of
      the engineered mutation in the final product to 100%. This method was used to
      generate a mutated glycoprotein K (gK) gene specified by HSV-1. A recombinant
      virus that carried the mutated gK gene caused extensive cell fusion of infected
      cells.

PMID- 8879588
TI  - Quantitative multiple competitive PCR of HIV-1 DNA in a single reaction tube.
AB  - A quantitative multiple competitive PCR (QMC-PCR) for determination of DNA copy
      numbers is described. Four competitive DNA templates for the env region of HIV-1
      were constructed with sizes longer (187 and 163 bp) or shorter (122 and 105 bp)
      than the 142 bp of the wild-type PCR product. Varying amounts of each of these
      competitors are introduced together with the sample into a single reaction tube.
      Since competitors and wild-type fragments share the same primer recognition
      sequence (SK68/SK69), amplification occurs according to the rate of the
      introduced copy numbers. The PCR products are run on an agarose gel, and the copy
      number of the sample is determined by analyzing the bands with a video
      densitometer and calculating the equivalence point in a linear regression plot.

PMID- 8879586
TI  - Simultaneous detection of microorganisms in soil suspension based on PCR
      amplification of bacterial 16S rRNA fragments.
AB  - The effect of buffer composition on simultaneous PCR amplification of 16S rRNA
      gene fragments of five bacterial species was examined using a number of different
      buffer systems. Tris-based PCR buffers at final concentrations of 10 mM proved
      unreliable. However, when the final concentration of Tris was increased to 75 mM,
      all five samples were routinely detected. The use of other buffers, 3-[(1,1
      dimethyl-2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid (AMPSO) and 3
      [cyclohexylamino]-2-hydroxy-1-propanesulfonic acid (CAPSO), resulted in PCR
      amplification of five products even at low final concentrations (10 mM). The
      presence of certain proteins in the amplification reaction could overcome an
      inhibitory effect seen when soil suspension was present in the reaction, as might
      occur when testing field samples for the presence of bacteria. Bovine serum
      albumin was found to be the most effective additive tested in overcoming
      inhibition.

PMID- 8879589
TI  - Fluorescence in situ hybridization method for measuring transfection efficiency.
AB  - We describe here the use of fluorescence in situ hybridization (FISH) to measure
      the transfection efficiency of the transient expression vector pCMVcat in
      lymphoblasts and fibroblasts. By using a pCMVcat probe, we can visualize the
      location of the plasmid after transfection and thus determine transfection
      efficiency. In this report, we show that, for transfection of pCMVcat by the
      diethylaminoethyl-dextran method, the transfection efficiency was about 15 and 70
      times greater in fibroblasts and lymphoblasts, respectively, when measured by the
      FISH method as compared to the efficiency measured by cotransfection with pCMV
      beta gal. Based on these results, we conclude that the FISH method is a highly
      sensitive, specific and direct measure of transfection efficiency of a transient
      expression vector and that it may be useful for evaluating laboratory assays in
      which the quantitative aspects of transfection and the effect of plasmid DNA
      damage on transfection efficiency are important.

PMID- 8879590
TI  - Efficiency of transduction by recombinant Sindbis replicon virus varies among
      cell lines, including mosquito cells and rat sensory neurons.
AB  - Recombinant alphaviruses have been used as vehicles for delivery and expression
      of heterologous genes in mammalian, avian and insect cell lines. We have used a
      Sindbis replicon virus (Sinreplac) able to express the E. coli lacZ gene to
      compare the efficiency of transduction in one insect, six mammalian cell lines
      and cultured rat dorsal neurons which apparently express beta-galactosidase over
      a 30-day time period. Results show that different cell lines were transduced with
      varying degrees of efficiency and that this efficiency could be improved in some
      cell lines by packaging the replicon with a helper derived from a more
      neurovirulent strain of Sindbis.

PMID- 8879591
TI  - Detection of cell-surface antigens using antibody-conjugated fluorospheres (ACF):
      application for six-color immunofluorescence.
AB  - Antibody-conjugated fluorospheres (ACF) were used to phenotype murine leukocytes
      by flow cytometric analysis. Multicolor immunofluoresence (beyond simultaneous 4
      color analysis) is limited by the availability of specific antibody-fluorochrome
      chrome conjugates and even further restricted by the spectral emission overlap of
      many of the fluorochromes when used in combination. Fluorospheres possessing
      unique excitation/emission spectra can provide much needed versatility to
      existing protocols of multicolor fluorescence. SKY BLUE (647 nm excitation, 730
      nm emission) fluorospheres conjugated to CD11b monoclonal antibody were used in
      combination with the monoclonal antibodies IAd-FITC, L3T4 (CD4)-PE, LYT2 (CD8)
      APC, THY1.2 (CD90)-biotin and B220 (CD45R)-RED613 for the simultaneous detection
      of six distinct cell-surface antigens in a mixed cell population. All
      fluorescence signals were resolved, and comparison of results from five-, six-
      and single-color samples indicated that the percentages of cells positive for
      specific surface antigens were equivalent.

PMID- 8879592
TI  - Sequential ELISA for cytokine levels in limited volumes of biological fluids.
AB  - We have developed an enzyme-linked immunosorbent assay (ELISA) for the sequential
      analysis of multiple cytokines in limited volumes of biological fluids, including
      gingival crevicular fluid (GCF) and fibroblast culture supernatants (CS). GCF and
      CS samples were assayed for multiple cytokines, including IL-1 beta, IL-6, IL-8,
      GM-CSF and IFN gamma. Immulon 3 microplates were coated with a monoclonal
      antibody, and a rabbit polyclonal antibody was used to detect the cytokine of
      interest. Biological samples (200 microL) were added to an anti-IL-1 beta-coated
      plate and incubated, and 175 microL of each sample were replicate transferred to
      an anti-IFN gamma-coated plate containing 25 microL/well of diluent. This was
      repeated in an identical fashion with sequential replicate transfers to an anti
      IL-8-coated and finally an anti-IL-6-coated plate. The cytokine standard was a
      pooled combination of the recombinant human cytokines that were included in the
      sequence. The plates were developed using an alkaline phosphatase-conjugated goat
      anti-rabbit IgG and NPP as the substrate. Individual ELISAs ranged in sensitivity
      from 30 to 2 pg/0.2 mL, with cross-reactivity between these cytokines of < 1%.
      Additionally, when the same samples were tested in the sequence ELISA vs. the
      individual ELISA, there was > 85% correlation between the two assays.

PMID- 8879593
TI  - Multiple fluorescence-based PCR-SSCP analysis using internal fluorescent labeling
      of PCR products.
AB  - The method to internally label PCR products with multiple colored fluorescent
      dyes was developed and applied to multiple fluorescence-based PCR single-stranded
      conformational polymorphism (MF-PCR-SSCP) analysis. PCR-amplified fluorescent DNA
      fragments, which were internally labeled by adding fluorescent dUTPs ([F]dUTPs)
      to the PCR mixture, were heat-denatured and applied to a nondenaturing
      polyacrylamide gel (SSCP gel) set on an automated DNA sequencer with a gel
      temperature-controlling system. The image data were analyzed by GENESCAN 672
      software. In spite of differences in species and amount of integrated [F]dUTPs,
      the SSCP profiles were not significantly affected, even by the different labeling
      methods used-internal labeling or post-labeling at the 3' ends-in regard to the
      three different [F]dUTPs examined. However, the salt concentration of the
      solution containing the DNA samples affected the SSCP profiles. The internally
      labeled [F]dUTP-containing DNA fragments beyond 1000 bp in length were
      successfully digested with restriction endonucleases and subjected to SSCP
      analysis. MF-PCR-SSCP analysis with internal fluorescence labeling affords a
      simple and sensitive method to detect alterations in DNA sequences.

PMID- 8879594
TI  - Dual luminescence-based reporter gene assay for luciferase and beta
      galactosidase.
AB  - A unique combined luminescence assay for firefly (Photinus pyralis) luciferase
      and beta-galactosidase (beta-gal) reporter gene products is described. Luciferase
      and beta-gal activities are determined with the same aliquot of cell lysate
      prepared from cells contransfected with both reporter genes, thereby reducing
      manual labor and increasing experimental accuracy. With the Dual-Light assay
      system, luciferase activity is measured first with an enhanced luciferase assay,
      followed by quantitation of beta-gal with Galacton-Plus chemiluminescent
      substrate and Sapphire-II enhancer. Highly sensitive detection of luciferase (2
      fg) and beta-gal (8 fg) is achieved with a dynamic range over seven orders of
      magnitude of enzyme concentration. Comparative analysis of both independent and
      combined (Dual-Light) detection methods for cells contransfected with luciferase
      and beta-gal reporter genes is also described.

PMID- 8879595
TI  - Full-length cDNA cloning and determination of mRNA 5' and 3' ends by
      amplification of adaptor-ligated cDNA.
AB  - An efficient cDNA amplification procedure is described for determining of the 5'
      and 3' ends of mRNAs and cloning full-length cDNAs. In this approach, a double
      stranded (ds) adaptor is ligated to both ends of a library of ds cDNA by T4 DNA
      ligase. This adaptor-ligated ds cDNA is then used to selectively amplify 5'- or
      3'-cDNA fragments by PCR with a combination of gene-specific and adaptor-specific
      primers. This is a unified method for 5' and 3' rapid amplification of cDNA ends
      (RACE) from the same adaptor-ligated ds cDNA template. A specially designed
      adaptor combines features of "vectorette PCR" and "suppression PCR" technologies
      that significantly reduce background during amplification. The application of
      "long and accurate PCR" (LA PCR) technology makes possible the amplification of
      large RACE products and full-length cDNAs with high fidelity to the original
      mRNA. We investigated efficacy and limitations of this PCR-based approach for
      cDNA cloning by amplification of 5'- and 3'-RACE fragments and full-length cDNAs
      of three members of the abundant human actin gene family (1.3-1.9 kb), the medium
      abundance transferrin receptor mRNA (5.0 kb) and the low-medium abundance insulin
      like growth factor II receptor mRNA (9.1 kb).

PMID- 8879596
TI  - Prediction of insulin resistance.

PMID- 8879597
TI  - Cardiac conduction with diltiazem and beta-blockade combined. A review and report
      on cases.
AB  - Sinus arrest or atrioventricular block are rare but serious adverse effects of
      diltiazem. The risk of developing such adverse reactions may be somewhat
      exacerbated by concomitant beta-adrenergic blocker therapy. In patients with
      hypertension or coronary heart disease, combination therapy with diltiazem and a
      beta-blocker usually enhances therapeutic benefit relative to monotherapy, but
      adverse effects attributable to this combination, especially in patients with
      left ventricular dysfunction or latent cardiac conduction deficits, may be
      limiting. Therefore, such combination therapy may not be suitable in patients
      with atrioventricular block grade I, bradycardia or hypotension, and patients on
      the combined therapy should always have their blood pressure, heart rate and
      atrioventricular conduction on ECG monitored. If combination therapy with
      diltiazem and propranolol or metoprolol is commenced, or in the case of impaired
      renal function, an adjustment of the beta-blocker dosage may be required.
      Clinical studies on the combined use of diltiazem and beta-adrenergic blockers
      mostly concern the treatment of angina pectoris in patients with coronary heart
      disease. Although very few cases of severe bradycardia and conduction
      abnormalities have been reported in patients with uncomplicated hypertension on
      diltiazem and beta-blockade combination, there seems to be a potential for the
      occurrence of significant conduction disturbances with the combined treatment,
      and precautions should apply also for hypertensive populations.

PMID- 8879598
TI  - Clinical implications of white coat hypertension.
AB  - OBJECTIVE: To determine the clinical implications of mild white coat hypertension
      (WCH). SUBJECTS AND METHODS: We studied 102 subjects (54 men, 48 women), 51 of
      whom were normotensive and 51 slightly hypertensive. None had ever received
      antihypertensive therapy. An ambulatory blood pressure (ABP) record (Accutracker
      II), a 24-h electrocardiogram and an echocardiogram were obtained from each, and
      each was examined by funduscopy. WCH subjects were compared with sustained
      hypertension (SH) subjects and with normotensives. RESULTS: Fifty-three percent
      of the hypertensives qualified as WCH. The ultrasonographic characteristics and
      the ABP variables of the WCH group differed significantly from those of
      normotensives, but not from those of the SH group. The prevalence of left
      ventricilar hypertrophy (LVH) in the SH group (62.5%) did not differ
      significantly from its prevalence in the WCH group (40.7%), but the prevalence
      among normotensives (17.6%) was significantly lower than in either of the other
      two groups. The WCH and SH groups did not differ significantly as regards the
      prevalence of hypertensive retinopathy (33.3% in the former, 58.3% in the
      latter). For no non-LVH, non-retinopathic subject, whether normotensive or
      hypertensive, were more than 18% of daytime diastolic ABP measurements > or = 90
      mmHg. Ultrasonographic findings were no better correlated with ABP than with in
      clinic BP measurements. Fundus findings correlated well with in-clinic BP and
      with numerous ABP parameters. Retinopathy, with or without LVH, was efficiently
      predictable among hypertensives on the basis of body mass index and the 24-h
      maximum of systolic BP. CONCLUSIONS: Myocardiac remodelling and vascular
      retinopathy develop early and in parallel in hypertensives, and both developments
      appear to involve determinants including body mass index and 24-h maximum
      systolic BP. WCH subjects, as defined by current ABP-based criteria, have cardiac
      and retinovascular characteristics different to normotensive subjects. Stricter
      criteria are needed to discriminate between hypertensives with and without the
      systemic developments that constitute the immediate source of risk to the
      hypertensives individual.

PMID- 8879599
TI  - Prediction models for insulin resistance.
AB  - A prediction model for estimating insulin resistance in hypertensive patients is
      presented. Body-mass index, serum triglyceride concentrations and liver enzyme
      activity in plasma correlate to insulin resistance determined with the
      euglycaemic, hyperinsulinaemic clamp technique. Prediction models using body-mass
      index and either triglycerides or serum alanine-amino transferase were equally
      good in predicting insulin resistance and gave results that were as reliable as
      those obtained in a model using fasting-insulin concentrations. The
      hyperinsulinaemic clamp had a reproducibility error of 14%, and body-mass index
      and serum triglycerides had a multiple correlation of 0.57 to the insulin
      sensitivity results. The model predicts insulin resistance with acceptable
      statistical power, whereas the power to predict high values of insulin
      sensitivity is less good.

PMID- 8879600
TI  - Hypertension in pregnancy and size at birth.
AB  - Low birth weight and high placental weight are associated with increased
      cardiovascular morbidity and mortality. Children born after hypertensive
      pregnancies have higher blood pressure than children born after normotensive
      pregnancies. Hypertension in pregnancy is considered a major risk factor for
      intrauterine growth retardation. The present study describes size at birth and
      perinatal characteristics in children born after hypertensive pregnancies. During
      five consecutive years 17,000 deliveries took place in the well defined
      geographic area of eastern Goteborg. Hypertension in pregnancy complicated 261
      pregnancies. For comparison 260 normotensive pregnancies, matched for maternal
      age and time of delivery, were used. Standard deviation score for birth weight
      and length were calculated according to reference standards for birth weight
      (BWSDS) and length (BLSDS) based on all Swedish births 1977-1981 (n = 475,588).
      Children born after hypertensive pregnancies had lower birth weight, were shorter
      and had a shorter gestational period as compared with children born after
      normotensive pregnancies. Head circumference and placental weight did not differ
      and there were no significant differences in BWSDS. It is concluded that
      hypertensive pregnancies are characterized by lower birth weight and shorter
      gestational period. However, intrauterine growth retardation is not a general
      characteristic of hypertension in pregnancy.

PMID- 8879601
TI  - The efficacy of felodipine ER on regression of left ventricular hypertrophy in
      patients with primary hypertension.
AB  - The aim of the study was to evaluate the efficacy over 1 year of of felodipine ER
      5 and 10 mg once daily (od) in 12 Caucasian patients with left ventricular
      hypertrophy secondary to primary hypertension. After a placebo period of 20 days,
      a physical examination and an echocardiography were performed in each patient.
      All patients started treatment with felodipine ER 5 mg. In 3 of the 12 patients
      the dose was increased to 10 mg od to control blood pressure (BP). BP was
      recorded every 2 weeks during the first 3 months, and at monthly intervals from
      the 3rd to the 12th months. An echocardiogram was taken at the end of the 3rd,
      6th, 9th and 12th months. At the end of the placebo period, the mean SBP/DBP (+/
      SD) was 178 +/- 11/104 +/- 5 mmHg. Mean SBP and DBP decreased significantly (p <
      0.001) during the first 2 months to 138 +/- 10/86 +/- 3 mmHg and remained at this
      level until the end of the study. Mean left ventricular mass index (LVMI)
      decreased from 170 +/- 33 g/m2 after the placebo period to 115 +/- 19 g/m2 after
      1 year (p < 0.01). It is concluded that felodipine ER 5 and 10 mg od over 1 year
      statistically significantly reduced both BP and LVMI.

PMID- 8879602
TI  - Twenty-four-hour ambulatory blood pressure and vasoactive hormones in valvular
      aortic disease.
AB  - The aim of this study was to assess the blood pressure profile and vasoactive
      hormones in valvular aortic disease. Thirteen aortic stenosis and/or aortic
      regurgitation patients were matched with 13 control subjects. Ambulatory blood
      pressure monitoring was performed for 24 h. Arterial and venous plasma
      concentrations of renin, angiotensin II, aldosterone, arginine vasopressin,
      atrial natriuretic peptide, immunoreactive endothelin and cyclic-GMP were
      measured. The mean 24-h blood pressure was higher in the patient group (94.9
      mmHg) compared with control subjects (88.2 mmHg) (p < 0.0001), despite no
      differences in daytime blood pressures. The nocturnal blood pressure fall was
      attenuated in the patients (systolic/diastolic blood pressure -8.5/-3.5; -20.3/
      14.3 mmHg (p < 0.001/p < 0.01)); in heart rate too the nightly fall was blunted
      in the patients (-4.8/ -13.4/min (p < 0.0013)). PRA, Ang II, AVP, ANP, ir-ET and
      cGMP were significantly increased in the patients compared to the controls.
      Nightly systolic blood pressure fall was inversely related to arterial (r = 
      0.75, p < 0.003) and venous (r = -0.65, p < 0.04) plasma renin activity and
      arterial aldosterone (r = -0.64, p < 0.05) in valvular aortic disease patients.
      In conclusion, valvular aortic disease patients have attenuated falls in blood
      pressure and heart rate during the night. Increased activity in the renin
      aldosterone system may be involved in this abnormal blood pressure regulation.

PMID- 8879603
TI  - The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a
      progress report.
AB  - OBJECTIVE: The Swedish Trial in Old Patients with Hypertension-2 (STOP
      Hypertension-2) was designed by a project group of the Swedish Hypertension
      Society to test whether the "newer" treatment alternatives (ACE inhibitors and
      calcium antagonists) are as good as, better or less good than, the "older" ones
      (beta-blockers and diuretics) in terms of preventing cardiovascular morbidity and
      mortality in elderly hypertensives. The aim of the present paper is to report on
      the progress of the study. DESIGN: Prospective, open trial with blinded end-point
      committee and centralized randomization (PROBE design). STOP-Hypertension-2 may
      be regarded as a scientific follow-up of the previously published Swedish Trial
      in Old Patients with Hypertension (STOP-Hypertensioon-1) (6) using the same study
      organization. SUBJECTS: By the end of 1994 when recruitment was stopped, 6628
      hypertensive men (34%) and women (66%) aged 70-84 (mean age 76) had been included
      at 312 Swedish health centres (out of approximately 850). In the whole cohort 11%
      are diabetics and 9% smokers. The mean total cholesterol value is 6.5 mmol/L.
      RESULTS: In the whole study cohort, blood pressure was lowered from 194/98 mmHg
      to 167/85 mmHg after one year. At the end of 1995, 319 fatal events (all-cause
      mortality) had been reported, corresponding to a mortality rate of 21.3 per 1000
      person-years. CONCLUSION: In STOP-Hypertension-2, 6628 elderly hypertensive have
      been randomized to three different treatment regimes: beta-blocker+diuretics (the
      active treatment arm in STOP-Hypertension-1), ACE inhibitors, or calcium
      antagonists. Their average lowering of blood pressure was 27/13 mmHg and end
      points have occurred at the expected rate. Thus, it should be possible to
      terminate STOP-Hypertension-2 within two to three years.

PMID- 8879604
TI  - Functional evidence of inhibitory reno-renal reflexes in spontaneously
      hypertensive rats.
AB  - The experiments were performed to study the role of the renal nerves and the reno
      renal reflexes in the control of water and sodium excretion in spontaneously
      hypertensive rats (SHR) compared to their normotensive controls, Wistar Kyoto
      (WKY) rats. Unilateral renal denervation in anaesthetized animals produced a
      slight, progressive decrease in arterial pressure in both WKY and SHR rats. The
      glomerular filtration rate temporarily increased in the kidney that underwent the
      denervation in the SHR group only. After unilateral renal denervation a sharp
      increase in water and sodium excretion from the ipsilateral kidney was observed
      in both WKY and SHR. One hour after the denervation, the percent changes in water
      and sodium excretion were smaller in WKY (+32 +/- 19% and +24 +/- 17%) than in
      SHR rats (+84 +/- 15% and +93 +/- 20%). In the kidney contralateral to the
      denervation a reduction in water and sodium excretion was observed and this
      reduction was prompter in SHR than in WKY rats. One hour after the denervation,
      the percent changes in water and sodium excretion were similar in WKY (-21 +/- 8%
      and -18 +/- 7%) and SHR (-19 +/- 6% and -19 +/- 7%). In control groups, sham
      denervation did not cause significant changes in glomerular filtration rate, and
      urinary water and sodium excretion. Arterial pressure slightly and progressively
      decreased in both control groups. Electrical stimulation of the efferent renal
      nerves performed in WKY and SHR produced similar decreases in renal blood flow,
      glomerular filtration rate, and water and sodium excretion in the two groups for
      the same frequencies of stimulation. As this finding indicates that renal targets
      in hypertensive rats are normally responsive to the neural drive, our data
      demonstrate that renal responses to unilateral renal denervation in hypertensive
      rats are equal to the responses observed in normotensive rats. Our results
      indicate that tonically active inhibitory renorenal reflexes normally operate in
      spontaneously hypertensive rats.

PMID- 8879605
TI  - Cardiovascular responses and interactions by neuropeptide Y in rats with
      congestive heart failure.
AB  - Neuropeptide Y (NPY) has been shown to potentiate the effects of various
      vasoactive agents in both in vitro and in vivo experiments. The present study was
      designed to investigate the potentiation effects of NPY on various
      vasoconstrictive agents and the influence of NPY on the dilatation effects of
      endothelin-1 in rats with congestive heart failure (CHF). CHF was induced by left
      coronary artery ligation. Sham-operated rats subjected to thoracotomy served as
      normal controls. Experiments in conscious rats were performed 4-6 weeks after
      coronary artery ligation or sham operation. The pressor responses of intravenous
      phenylephrine (12.5 nmol/kg), endothelin-1 (400 pmol/kg) and angiotensin II (10
      ng) but not tyramine (40 micrograms) were significantly decreased in CHF rats
      compared with sham-operated rats (p < 0.01). In sham-operated rats, subthreshold
      dose of NPY (0.1 microgram/kg/min) potentiated the pressor responses of all the
      agonists (p < 0.05). In CHF rats, significant enhancement of mean arterial
      pressure (MAP) by subthreshold dose of NPY was observed with angiotensin II (p <
      0.05). The MAP was enhanced by 45.4% in CHF and 40.6% in sham-operated rats
      respectively. NPY did not enhance the pressor responses induced by phenylephrine,
      endothelin-1 or tyramine in CHF rats. The initial decrease of MAP after bolus
      injection of endothelin-1 was observed in both CHF and sham-operated control
      rats, and magnitude of this response was similar in both groups. Subthreshold
      dose of NPY significantly reduced the vasodilatation effect of endothelin-1 in
      CHF (p < 0.05) but not in normal control rats. We conclude that NPY potentiates
      pressor effects of angiotensin II and reduces vasodilatation effects of
      endothelin-1 in rats with CHF. These effects of NPY may contribute to the
      increased vascular tone in CHF.

PMID- 8879606
TI  - Third generation calcium antagonists.

PMID- 8879608
TI  - A pilot study of busulfan and melphalan as preparatory regimen prior to
      allogeneic bone marrow transplantation in refractory or relapsed hematological
      malignancies.
AB  - In this pilot study; we assessed the immunosuppressive and the antileukemic
      potential of a combination of busulfan and melphalan prior to allogeneic BMT in
      25 adult patients with refractory or relapsed hematological malignancies. Twelve
      patients were transplanted for acute myeloid leukemia (relapse: five patients;
      primary refractory: four patients; second remission: two patients), two patients
      for primary refractory acute lymphoblastic leukemia, nine patients for chronic
      myelogenous leukemia (accelerated phase: six patients; blastic phase: three
      patients) and two patients for primary refractory lymphoma. All received an
      unmanipulated marrow from HLA-identical siblings. All patients but one engrafted
      (median time to ANC > or = 0.5 x 10(9)/l = 17 days, to platelets > or = 50 x
      10(9)/l = 29 days). Full chimerism was documented in the seven evaluable
      patients. The probability for developing acute GVHD was 58%. Complete remission
      was obtained in 17/18 measurable patients. With a 42 month median follow-up,
      eight patients are alive in unmaintained remission. The 4-year probabilities for
      relapse, survival, and DFS are respectively: 42%, 35%, and 31%. These results
      show that the combination of busulfan and melphalan ensures an effective
      immunosuppression allowing long-term engraftment. This regimen can provide long
      term disease-free survival in patients with high-risk disease and thus represents
      an interesting alternative to the CY and/or TBI-containing regimens.

PMID- 8879607
TI  - Allogeneic bone marrow transplantation for children with acute lymphoblastic
      leukemia conditioned with busulfan, cyclophosphamide and melphalan.
AB  - Children with acute lymphoblastic leukemia (ALL) undergoing allogeneic bone
      marrow transplantation (BMT) using total body irradiation (TBI)-containing
      conditioning regimens are at risk of substantial late sequelae affecting growth
      and endocrine functions. This has lead to the use of non-TBI or chemotherapy
      conditioning regimens for ALL patients in many centers. However, it is unknown
      whether chemotherapy conditioning results in improved antileukemic efficacy or
      reduced transplant-related toxicity. We report our experience using a
      chemotherapy conditioning regimen (busulfan (Bu), cyclophosphamide (CY) and
      melphalan (Mel)) in 26 consecutively enrolled children with ALL (group I). At a
      median follow-up of 58 months, event-free survival (EFS) for Bu/CY/Mel-treated
      patients was 27% (+/- 8.7), while the leukemic relapse rate was 49% (+/- 13).
      Regimen-related toxicity was severe in these patients: overall treatment-related
      mortality was 42%, while 50% of patients had interstitial pneumonitis and 35% of
      patients had severe hemorrhagic cystitis. A historical control group of 25
      consecutively enrolled patients, mostly treated with TBI-containing regimens
      (group II), had an EFS of 36% (+/- 9.6%) and a leukaemic relapse rate of 45% (+/-
      11) at a median follow-up of 117 months. We conclude that the Bu/CY/Mel
      conditioning regimen leads to severe transplant-related toxicity and did not
      significantly improve leukemic relapse rates.

PMID- 8879609
TI  - Second allogeneic transplants for leukemia using blood instead of bone marrow as
      a source of hemopoietic cells.
AB  - There is increasing interest in blood cell transplants (BCT) from normal donors
      as an alternative to BMT. Ten patients with relapsed or persistent leukemia after
      BMT received intensive cytotoxic conditioning followed by allogeneic BCT. Three
      BCT were from single-antigen mismatched donors; two of the corresponding
      recipients had rejected a BMT from the same donor. Two patients received BCT from
      a different donor (one matched, one single-antigen mismatched). The other six BCT
      were from the same, fully matched, bone marrow donors. Donors were given G-CSF to
      mobilize progenitor cells which were collected by a single 2-4 h leukapheresis.
      Methotrexate, CsA and folinic acid were used for GVHD prophylaxis for all
      transplants but CsA was discontinued sooner after BCT than after BMT. One patient
      died without engraftment having rejected a BMT from the same single-antigen
      mismatched donor 4 years previously. Nine patients had granulocyte recovery at a
      median of 14 days, up to 6 days faster than with their previous BMT. Platelet
      recovery was also 2-6 days faster than with BMT in four previously engrafting
      patients. Four patients died without platelet recovery after BCT within a year of
      BMT, three of treatment-related toxicity and one of relapse. Two patients
      developed grade II acute GVHD. Of six patients given BCT more than a year from
      BMT, four, all with acute leukemia, survive 7, 14, 29 and 29 months after BCT and
      one relapsed at 7 months. All four survivors developed chronic GVHD. These
      results indicate that BCT may be useful therapy for relapse occurring more than a
      year after BMT.

PMID- 8879610
TI  - Peripheral blood stem cell support does not accelerate haemopoietic recovery from
      miniBEAM chemotherapy.
AB  - Intermediate-dose salvage therapy is frequently given for relapsed and resistant
      lymphomas and is usually intensely myelosuppressive. In an attempt to reduce the
      haematological toxicity of miniBEAM, one of the commonly used salvage regimens,
      peripheral blood stem cell (PBSC) support was given to 21 consecutive patients
      who received miniBEAM chemotherapy. The outcome was compared with a non
      randomised control group of consecutive patients who were similar to the
      supported group apart from the fact that it was not possible to collect PBSC
      before miniBEAM therapy. Apart from a small, marginally significant difference
      between the supported and unsupported groups in the number of days for which
      intravenous antibiotics were required, there were no other differences between
      the two groups in supportive care required and times to haematological recovery.
      In conclusion, PBSC support does not accelerate haematological recovery from
      miniBEAM therapy.

PMID- 8879611
TI  - Fibroblasts retrovirally transfected with the human IL-3 gene initiate and
      sustain multilineage human hematopoiesis in SCID mice: comparison of CD34
      enriched vs CD34-enriched and in vitro expanded grafts.
AB  - Peripheral blood progenitor cells (PBPCs) obtained from cytapheresis products
      (CPs) of tumor patients undergoing mobilizing chemotherapy for PBPC support and
      dose-intensified anticancer chemotherapy initiate multilineage human
      hematopoiesis after intraperitoneal (i.p.) transplantation into young severe
      combined immunodeficient (SCID) mice. The engraftment process was significantly
      accelerated by subcutaneous cotransplants of a rat fibroblast cell line stably
      transfected with a retroviral vector carrying the human interleukin-3 (hIL-3)
      gene and producing sustained in vivo levels of circulating human IL-3 over a
      prolonged period of time. These cotransplants were found to provide a suitable
      microenvironment for i.p. transplanted CD34-positive cells separated from PBPC
      preparations using immunomagnetic beads. Flow cytometry analysis and
      immunocytology revealed that selected PB CD34- cells, more than 90% pure, were
      capable of initiating and sustaining a productive multilineage hematopoiesis
      preferentially within the hIL-3-secreting cotransplants followed by release of
      mature human cells into the circulation, spleen and thymus. The percentages of
      human cells found in hIL-3 cotransplants 8 weeks post-transplantation (p.t.) were
      generally higher than those measured after transplantation of complete CP
      mononuclear cells containing comparable doses of CD34-positive cells. When
      selected PB CD34+ cells that were expanded ex vivo with combinations of human
      hematopoietic growth factors including the c-kit ligand (KL), interleukin (IL)-1
      beta, IL-3, IL-6, erythropoietin (EPO) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) for 14 days were grafted to cotransplant-carrying
      SCID mice, a considerable loss of their proliferative potential was observed
      regardless of the HGF combination used. When experiments with grafts of selected
      PBPC were compared to those performed with selected/expanded PBPC on a per CD34+
      cell basis the results revealed that over a dose range of 0.3 to 1.0 x 10(6)
      cells/graft the in vivo proliferative capacity of expanded cells was reduced by a
      factor of 2 to 3.

PMID- 8879612
TI  - Hematopoietic potential of IL-2-cultured peripheral blood stem cells from breast
      cancer patients.
AB  - Patients receiving autologous transplants for various malignancies generally
      experience an increased incidence of relapse compared with patients receiving
      unmanipulated allogeneic transplants. We initiated a protocol for IL-2 activation
      of peripheral blood stem cells (PBSC) for induction of in vitro and in vivo
      autologous graft-versus-tumor (GVT) activity in patients with breast cancer. In
      this study we analyzed the effects of 24 h of IL-2 incubation on the
      hematopoietic potential of PBSC from these patients. Cells collected by
      leukapheresis were first cryopreserved and stored in liquid nitrogen, then thawed
      rapidly and incubated with IL-2 in a serum-free system for 24 h, with samples
      analyzed before and after incubation. Although there was a significant drop in
      mononuclear cells (MNC) (from 4.5 to 3.7 x 10(8)/kg) and CD34+ cells (from 12.3
      to 7.5 x 10(6)/kg) after 24 h in culture, there was no significant change in
      colony-forming units (CFU) (from 12.5 to 11.5 x 10(5)/kg). Time to engraftment
      (neutrophils: < 0.5 x 10(9)/l; platelets: > 20 x 10(9)/l) was comparable to a
      cohort of similar patients receiving non-cultured PBSC transplants. These results
      indicate that mobilized frozen/thawed PBSC which have been cultured in IL-2 for
      24 h retain adequate potential for hematopoietic reconsistution in this group of
      patients.

PMID- 8879613
TI  - Syngeneic marrow transplantation in patients with multiple myeloma.
AB  - Eleven patients with advanced multiple myeloma (MM) received syngeneic marrow (n
      = 10) or peripheral blood stem cell (n = 1) transplants following
      cyclophosphamide (CY) and total body irradiation (TBI) (n = 8), busulfan (Bu) and
      CY (n = 1), Bu, CY and TBI (n = 1) or Bu, melphalan and thiotepa (n = 1). At the
      time of transplant one patient had stage II and 10 patients had stage III
      disease. Four patients had refractory disease, two had chemotherapy sensitive
      disease and five had progressed after an initial response to chemotherapy. The
      median time from diagnosis to transplant was 353 days (range 176-6118). After
      transplant, the median time to achieve granulocytes of 0.5 x 10(9)/l and
      platelets of 20 x 10(9)/l was 12 days (range 9-20) and 12 days (9-27),
      respectively. One patient died of interstitial pneumonia syndrome on day 32 and
      one died of veno-occlusive disease of the liver on day 44 post-transplant, and
      these were unevaluable for response. Five of nine evaluable patients achieved a
      complete response (CR), three a partial response, and one patient had no
      response. Three patients who did not achieve CR died of progressive disease 106,
      142 and 321 days post-transplant. Of five patients who achieved a CR, three
      relapsed on days 539, 737 and 1706 and died on days 1759, 1596 and 1736,
      respectively; one patient died of myelodysplastic syndrome on day 1407 without
      evidence of MM and one patient is alive and disease-free 3297 days after
      transplant. One of the two long-term survivors has a persistent monoclonal
      protein in the blood 15 years post-transplant. These data show that high-dose
      therapy and infusion of normal syngeneic marrow cells can cure a small fraction
      of patients with MM. However, the majority of patients did not achieve durable
      CR, demonstrating the need for improved transplant conditioning regimens, earlier
      transplant or additional post-transplant treatment strategies when syngeneic
      transplants are performed.

PMID- 8879614
TI  - Bone marrow transplantation for the treatment of haematological disorders in
      Down's syndrome: toxicity and outcome.
AB  - We report 18 patients with Down's syndrome who underwent bone marrow
      transplantation, and review nine previously published patients. The indications
      for transplant in the combined group of 27 patients were acute lymphoblastic
      leukaemia in 14 cases (52%), acute myeloid leukaemia in 11 cases (41%) and
      aplastic anemia in two cases (7%). Transplants were autologous in five cases
      (19%) and allogeneic in 22 cases (81%); of the 22 allogeneic transplants, 16
      donors were HLA-matched siblings. In all patients the conditioning regimen
      included total body irradiation of 7.5 Gy or more, and/or contained
      cyclophosphamide of 120 mg/kg or more. Seven patients (26%) had fatal pulmonary
      disease including pneumonitis and pulmonary hemorrhage. Five patients (19%) had
      significant airway problems including three with severe mucositis who required
      intubation for airway protection, one with severe mucositis with partial airway
      obstruction that required observation in the intensive care unit but did not
      require intubation, and one with Candida albicans laryngitis with development of
      a glottic web. Nineteen patients (70%) survived beyond 100 days post-transplant.
      There was no clear association between 100-day survival and the use of any
      particular agent or regimen used for conditioning or graft-versus-host disease
      prophylaxis, and the majority of patients tolerated high-dose cyclophosphamide,
      high-dose cytosine arabinoside, high-dose busulfan, total body irradiation,
      cyclosporin A, and methotrexate. There appeared to be more early deaths in
      patients who received the combination of cyclophosphamide and total body
      irradiation, compared with those receiving the combination of busulfan and
      cyclophosphamide or those receiving the combination of cytosine arabinoside and
      total body irradiation. Also, the use of methotrexate was associated with a
      greater number of early deaths, compared with cyclosporin A. At 3 years, life
      table estimates of freedom from relapse, relapse-free survival and survival were
      75%, 44% and 48%, respectively. The estimated cumulative risk of death due to a
      non-leukaemic cause at 3 years was 39%. The data show that Down syndrome patients
      can tolerate the commonly used transplant conditioning regimens with acceptable
      toxicity; however, there is a strong suggestion in the data that the rates of
      life-threatening and fatal toxicity are higher than would be expected to occur in
      patients without Down's syndrome. Patients with Down's syndrome may have a
      predisposition to fatal pulmonary complications and reversible airway problems
      during the immediate post-transplant period.

PMID- 8879615
TI  - Residual leukemia and immunomagnetic bead purging in patients with BCR-ABL
      positive acute lymphoblastic leukemia.
AB  - Residual leukemia was evaluated in autologous bone marrow grafts harvested in
      first (n = 11) or second (n = 3) complete remission from 14 patients with BCR-ABL
      positive acute lymphoblastic leukemia after treatment according to the German
      multicenter ALL protocols. The intervals from diagnosis to BM harvest were median
      159 (range 78-463) and from preceding chemotherapy to BM harvest median 39 (range
      26-69) days, respectively. A limiting log(10)-dilution RT-PCR was used to
      semiquantify BCR-ABL-positive cells. All autografts appeared to be significantly
      contaminated with residual leukemic cells. The BCR-ABL-specific titers ranged
      from 1:10(3) to 1:10(6) (median 1:10(4)) above the limit of detection. This was
      the rationale to purge the grafts using two cycles of IgM anti-CD10, CD19, and
      AB4 MoAbs-coated immunomagnetic beads (IMB). Purging depleted median 3 (range 2
      4) logs of residual leukemia, resulting in a median 1:10(1) (range 1:10(0) to
      1:10(3)) postpurge BCR-ABL-specific titer. The second purging cycle accounted for
      1 log of depletion. The mean +/- s.e.m. post-purge recoveries of MNC and CFU-GM
      were 59 +/- 4%, and 61 +/- 9%, respectively. We conclude that all BCR-ABL
      positive ALL patients achieving CR by cytological criteria have critically high
      levels of residual leukemia in their bone marrow, which can be reduced by median
      3 log using immunomagnetic bead purging.

PMID- 8879616
TI  - Chemopurging of peripheral blood-derived progenitor cells by alkyl
      lysophospholipid and its effect on haematopoietic rescue after high-dose therapy.
AB  - One reason for relapse after high-dose tumor therapy with subsequent autologous
      stem cell transplantation is tumor cell contamination of the graft. Removal of
      tumor cells from bone marrow grafts by chemopurging with the ether lipid
      edelfosine has been established as an effective and simple method. When compared
      with bone marrow derived grafts, progenitor cells from peripheral blood have
      considerably reduced the haematological recovery times. However, this advantage
      is put at risk by the nonspecific haematotoxic activity of the purging agent. We
      therefore compared the in vitro recovery of peripheral blood derived progenitor
      cells (PBPC) from either non-purged (n = 41) or purged (75 micrograms/ml of ether
      lipid for 4 h at 37 degrees C, n = 48) leukapheresis products. The recovery of
      CFU-GM after cryopreservation was 63 +/- 4% without and 48 +/- 3% with purging (P
      = 0.007). After high-dose therapy, patients (n = 37) received similar amounts of
      either non-purged (n = 17) or purged (n = 20) autologous PBPC. The median
      haematological recovery times (non-purged vs purged) to > 500 WBC/microlitres
      were 9.0 vs 8.5 days after transplantation, to > 2000 PMN/microlitres 10.5 vs
      10.0 days, and to > 50,000 PLT/microlitres 15.5 vs 14.0 days. All differences
      were statistically not significant. We conclude that ether lipid purging of PBPC
      leads to a significant, however tolerable loss of progenitor cells in vitro, and
      that haematological recovery times after high-dose therapy are identically short,
      provided similar amounts of PBPC are reinfused.

PMID- 8879617
TI  - Association between antibodies reactive with neutrophils, rate of neutrophil
      engraftment, and incidence of post-engraftment neutropenia following BMT.
AB  - Previous reports have suggested that antibodies reactive with neutrophils (ARN)
      are frequently detectable in patients undergoing bone marrow or blood stem cell
      transplantation (BMT), and that such antibodies result in steroid-responsive
      delayed neutrophil engraftment or steroid-responsive post-engraftment neutropenia
      in some patients. However, the true incidence and significance of ARN in the BMT
      setting remain poorly established because most of the published data are in the
      form of retrospective case reports. Therefore, we prospectively studied the
      incidence of ARN, the rate of neutrophil engraftment, and the incidence of post
      engraftment neutropenia in a cohort of 40 BMT candidates. Sixteen of the 36
      evaluable patients (44%) had detectable ARN following transplant vs none of 25
      concurrently studied healthy controls (P < 0.0001). Patients with detectable ARN
      in the post-transplant period recovered to an absolute neutrophil count (ANC) of
      500 x 10(9)/l a median of 3.5 days later than patients without detectable ARN;
      multivariate analysis controlling for the potential effects of diagnosis,
      conditioning regimen, amount of prior therapy, and other factors revealed that
      only the administration of hematopoietic growth factors (P = 0.008) and the
      presence of ARN in the post-transplant period (P = 0.016) were independently
      predictive of the rate of neutrophil engraftment following BMT. Four of the 16
      patients with detectable ARN (25%) satisfied previously published criteria for
      post-engraftment neutropenia, ie a fall in the ANC to less than 500 x 10(9)/l for
      at least 2 consecutive days, following initial engraftment to an ANC of at least
      1000 x 10(9)/l for at least 2 consecutive days. In contrast, none of the 20
      patients without detectable post-transplant ARN developed post-engraftment
      neutropenia. Multivariate analysis revealed that only the presence of ARN in the
      post-transplant period (P = 0.022) was independently predictive of post
      engraftment neutropenia. All four patients with ARN-associated post-engraftment
      neutropenia responded to steroid-based therapy. These prospectively gathered data
      support previously published primarily case report data suggesting that ARN occur
      frequently following BMT and are associated with an increased incidence of
      delayed neutrophil engraftment and post-engraftment neutropenia. As is the case
      in the non-transplant setting, ARN-associated neutropenia occurring following BMT
      may respond to steroid-based therapy.

PMID- 8879618
TI  - Foscarnet for pre-emptive therapy of CMV infection detected by a leukocyte-based
      nested PCR in allogeneic bone marrow transplant patients.
AB  - Fifteen allogeneic BMT patients in a phase II study were given foscarnet 60 mg/kg
      twice daily for 14 days as pre-emptive therapy against CMV disease. CMV infection
      was diagnosed by a leukocyte-based nested PCR. All 15 patients were evaluable for
      toxicity. One patient did not fulfill the inclusion criteria of two consecutively
      positive CMV PCR tests and therefore was not evaluable for efficacy. Thus, 14 of
      15 patients were evaluable for development of CMV disease. None of the patients
      developed CMV disease and all 14 assessable patients had a negative CMV isolation
      at the end of therapy. None of the 15 patients had to discontinue therapy due to
      toxicity. Six patients reported mild gastrointestinal disturbances, three
      patients headaches, and three patients mild urethritis or hemorrhagic cystitis.
      Serum-electrolyte disturbances were common including abnormal magnesium,
      potassium and calcium levels. Two patients developed mild serum-creatinine
      increases requiring adjustment of the foscarnet dosage according to protocol. We
      conclude that a dosage of foscarnet of 60 mg/kg given twice daily seems to be
      safe and effective in preventing CMV disease in allogeneic BMT recipients. A
      study comparing foscarnet and ganciclovir is indicated.

PMID- 8879619
TI  - Tacrolimus (FK506)-induced cerebral blindness following bone marrow
      transplantation.
AB  - Three patients who developed acute onset of cerebral blindness within 5-47 days
      of BMT using tacrolimus (FK506) as primary GVHD prophylaxis are described. This
      syndrome has been described with the use of cyclosporin A (CsA) and FK506 in
      solid organ transplant recipients. CsA-induced cerebral blindness has also been
      noted in BMT recipients but to date there have been no reports of this
      complication in BMT patients receiving FK506. We have noted a striking similarity
      in the clinical and radiographic presentations between these patients and those
      with CsA-associated cerebral blindness. Reversibility within 1-2 weeks of onset
      and the potential for substitution of CsA for FK506 in these patients is
      described.

PMID- 8879620
TI  - Fatal cyclophosphamide cardiomyopathy: its clinical course and treatment.
AB  - Acute decompensating cardiomyopathy induced by cyclophosphamide is usually
      irreversible. To investigate the clinical course and the outcome of therapy, 13
      patients (1.7%) with grade III acute cardiomyopathy and hypotension who were
      treated with ablative transplant regimens between January 1980 and September 1995
      were analyzed. Eight of nine patients died of acute fatal restrictive
      cardiomyopathy with unresponsive hypotension (ARCH), whereas three of four
      patients who survived the initial episode died of subacute congestive heart
      failure (SCHF). Acute fatal restrictive cardiomyopathy was characterized with
      extreme sensitivity to volume overload, myocardial edema and a rapidly fatal
      course. It was associated with progressive, unresponsive hypotension, reduced
      left ventricular stroke work index (LVSWI: 29.29 +/- 9.74 g-m/beat/m2) and
      markedly reduced systemic and pulmonary vascular resistance indices (SVRI: 429.72
      +/- 168.84, PVRI: 58.63 +/- 45.08 dyne.sec/cm5.m2). Subacute CHF was identified
      by myocardial edema, dilated chambers and biventricular pump failure represented
      by decreases in fractional shortening (FS: 19.5 +/- 4.9%). Of 10 patients who
      received conventional therapy, nine died and one sustained chronic CHF. One of
      three patients with ARCH on antioxidant therapy of ascorbic acid and theophylline
      survived the episode. The data suggests peripheral vascular collapse may also be
      responsible for fatal ARCH.

PMID- 8879621
TI  - Quality of life in breast cancer patients before and after autologous bone marrow
      transplantation.
AB  - The purpose of this study was to compare pre- and posttreatment quality of life
      (QOL) in breast cancer patients undergoing high-dose chemotherapy with autologous
      bone marrow transplantation (ABMT). Fifty-two female breast cancer patients were
      assessed on overall QOL, mood status, and social support before transplantation.
      After ABMT, 24 patients were assessed on the same measures as well as a measure
      of depressive symptoms and specific concerns identified in a structured
      interview. Mean pre- and post-transplant scores on the quality of life measure,
      mood scores and social support were not significantly different. Eight patients
      (33%) reported depressive symptoms post-transplantation. In the structured
      interview, a percentage of patients reported concerns in the following areas: job
      or work situation (25%); finances (42%); general physical health (50%); general
      frame of mind (25%); appearance (33%); health or life insurance (37%); personal
      or intimate physical relations (33%); planning for the future (38%). QOL and mood
      following ABMT improved slightly and compares favorably with breast cancer
      patients treated with conventional treatment. However, approximately 30% of
      patients had problems with sexuality, fatigue and depressive symptoms and may
      need follow-up psychosocial care in these areas. ABMT may pose no more threat to
      quality of life than conventional chemotherapy.

PMID- 8879622
TI  - Anxiety as a possible predictor of acute GVHD.
AB  - In order to determine the influence of anxiety on the development of BMT
      complications and survival, we analysed data on 35 consecutive patients
      undergoing BMT in our Centre between June 1992 and December 1994. All patients
      received bone marrow from HLA-identical MLC non-responsive siblings. For GVHD
      prophylaxis, all patients received cyclosporin (CsA) and short methotrexate
      (MTX). The diagnosis and severity of acute GVHD were defined according to the
      Seattle Transplant Team criteria. The patients were tested with the Spielberger
      STAI test as a measure of anxiety as a state (STAI-S) and as a trait (STAI-T).
      The STAI-S/1 and STAI-T/1 were performed during the first week of isolation (day 
      5 to day -3 prior BMT) and STAI-S/2 and STAI-T/2 at the end of the discharge from
      laminar air flow units (day +35 to day +40 post-transplant). During isolation all
      patients had daily psychiatric support. Out of 35 patients, 31 (89%) fulfilled
      the STAI-S and STAI-T during the first week and at discharge from laminar air
      flow isolation. The level of anxiety at the beginning of isolation as measured by
      STAI-S/1 and STAI-T/1 tests had been significantly higher in patients who
      subsequently developed acute grade II-IV GVHD as compared to patients with GVHD
      grade 0-I (P < 0.001), irrespective of age, sex or stage of the disease prior to
      BMT. In those patients who died, the STAI-S/1, STAI-T/1 and STAI-T/2 tests had
      been almost identical to those of surviving patients, while STAI-S/2 had been
      significantly higher (P = 0.034). These data clearly indicate an association
      between the level of anxiety and the risk for BMT complications, but this should
      be confirmed in further controlled clinical trials.

PMID- 8879623
TI  - Prognostic factors affecting leukemia relapse after allogeneic BMT conditioned
      with cyclophosphamide and fractionated TBI.
AB  - Between June 1985 and May 1992, 94 consecutive patients with acute myeloid
      leukemia (AML = 28), acute lymphoblastic leukemia (ALL = 27) and chronic
      myelogenous leukemia (CML = 39), were transplanted using genotypically HLA
      identical marrow donors. All were conditioned with cyclophosphamide (CY) plus 12
      Gy fractionated TBI. Graft-versus-host disease (GVHD) prophylaxis consisted of
      cyclosporin A alone in nine patients and methotrexate-cyclosporin A in 85
      patients. Forty-eight patients developed grades II-IV acute GVHD and 24 of 68
      patients who survived at least 100 days developed chronic GVHD. The 5-year
      actuarial probability of survival, event-free survival and relapse were 41 +/-
      5%, 37 +/- 5% and 37 +/- 6%, respectively. In multivariate analysis, an increased
      risk of leukemia relapse was associated with (1) absence of chronic GVHD (P =
      0.017), (2) advanced disease at transplant (P = 0.034) and (3) diagnosis of AML
      (P = 0.047). Our results confirm that disease status at transplant and chronic
      GVHD are the more important risk factors associated with leukemia relapse, and
      suggest that CY-TBI has only a partial role in eradicating leukemia in AML.

PMID- 8879624
TI  - Improved yield of peripheral blood progenitor cells on the Cobe Spectra.
AB  - The efficiency of leucapheresis using the Cobe Spectra depends on the observation
      of the operator to monitor the haematocrit (Hct) in the collection line at the
      recommended Hct of 1%. Cells were harvested by processing 3 x total blood volume
      (TBV) over 3-4 h. During the harvest the manual Hct and the colony-forming units
      granulocyte-macrophage (CFU-GM) concentrations were analysed in the collection
      line in the observed Hct range of 1-7.5%. There was a correlation between the
      manual and observed Hct (r = 0.97). The CFU-GM concentration was normalised to
      allow comparison between patients. The increase was statistically significant
      between 1-2% (P = 0.04) and 1-3% Hct (P = 0.05). The increase in CFU-GM
      concentration remained at the termination of harvest, indicating that not all
      available CFU-GM were harvested. The optimum concentration of progenitor cells
      was found to be at 3% Hct. We postulate that this may permit the collection of
      sufficient cells on one occasion to allow PBPC autografting in the majority of
      patients who respond to mobilisation.

PMID- 8879625
TI  - Isolation of CD34+ hematopoietic progenitor cells in chronic myeloid leukemia by
      magnetic activated cell sorting (MACS).
AB  - We have evaluated an easy and fast immunomagnetic method for positive selection
      of cells expressing the CD34 antigen from BM, peripheral blood (PB) and apheresis
      products (AP) of CML patients and healthy adults (HA) in order to further
      characterize them by immunophenotypic analysis. From an initial frequency of
      CD34+ cells in the original sample of 1.8 +/- 1.7%, CD34+ cells were rapidly and
      efficiently enriched up to 91.5 +/- 6.4% by high-gradient magnetic cell sorting
      (MACS) (yield 53 +/- 21%). A five-dimensional flow cytometric analysis of the
      immunomagnetic isolated CD34+ cells demonstrated little overlap between CD34+HLA
      DRlo and CD34+CD38lo subpopulations in both BM-HA and in BM-CML. Only 16 and 6%
      of the CD34+HLA-DRlo and CD34+CD38lo cells respectively, showed lack of
      expression of both Ag (CD34+HLA-DRloCD38lo) in BM-CML samples. Between 60 and 70%
      of the CD34+ cells expressed the stem cell factor (SCF) receptor (c-KIT, CD117)
      and there were no differences between BM-HA and BM-CML patients. Moreover, more
      than 60% of the CD34+HLA-DRlo cells, co-expressed c-KIT. MACS-enriched BM-CD34+
      cells showed normal hematopoietic colony formation in vitro in all the sources
      analyzed with a higher colony-forming efficiency than the unfractionated sample
      (MNC).

PMID- 8879626
TI  - Target value tailored (TVT) apheresis approach for blood progenitor cell
      collection after high-dose chemotherapy and rh-G-CSF.
AB  - Twenty-eight patients with different hematological diseases (17 non-Hodgkin's
      lymphoma, one Hodgkin's disease and 10 multiple myeloma) underwent peripheral
      blood progenitor cell (PBPC) collection after cyclophosphamide 7 g/m2 and rh-G
      CSF. Fifty-eight leukaphereses were carried out with a fully automated PBPC
      collection procedure. Progenitor cell release was monitored by standardized
      determination of CD34+ cells in the peripheral blood. After a profound aplasia, a
      continuous increase in CD34+ cells in the peripheral blood was seen for at least
      3-4 days. In 82% of our patients more than 2.5 x 10(6) CD34/kg could be collected
      using a standard apheresis of 10 l. There was a high correlation between the
      CD34+ cells in the peripheral blood and CD34+ cells/kg harvested. (r2 = 0.91). A
      relatively constant ratio (median 14.3, range 3.2-22.6) was found between CD34+
      cells/kg and CFU-GM/kg. Based on the CD34 values of the pre-apheresis blood and
      the body weight of an individual patient and using the mathematical model of
      regression analysis (y = mx + b) for the correlation between the CD34+
      cells/microliter in the pre-apheresis blood and the CD34+ cells/kg, it was
      possible to create a formula allowing for target value tailored apheresis. Using
      this formula, the blood volume which needs to be processed in order to harvest a
      desired number of CD34+ cells/kg can be calculated. This strategy can be applied
      to reduce the time for and the number of aphereses. Nineteen leukaphereses were
      carried out applying the formula. In 18 of 19 leukaphereses the expected CD34+/kg
      values were correctly achieved or exceeded. The formula was most reliable when
      the CD34 value was higher than 15/microliter and when the WBC count was below 20
      x 10(9)/l in the pre-apheresis blood. For mobilizations using hematopoietic
      growth factors alone our formula is not applicable, because in most cases the pre
      apheresis white blood cell count is higher than 20 x 10(9)/l and the collection
      efficacy of lymphomonocytoid cells decreases with a high pre-apheresis white
      blood cell count. The formula also works with other mobilization regimens that
      induce a pronounced aplasia.

PMID- 8879627
TI  - Benefits of blood cell transplant cryopreservation with oxypolygelatine
      (Gelifundol) plasma substitute.
AB  - In two groups of 11 patients with poor prognosis malignancies undergoing high
      dose sequential chemotherapy, we have evaluated the cryopreservation of blood
      cell transplants with oxypolygelatine-containing (55% oxypolygelatine, 6%
      hydroxyethylstarch, 5% dimethyl sulfoxide) vs standard human serum-containing
      (55% human serum, 6% hydroxyethylstarch, 5% dimethyl sulfoxide) cryoprotectant
      mixtures. Evidence is presented demonstrating that substitution of human serum
      proteins with oxypolygelatine has no detrimental effect either in vitro on the
      post-thawing recovery of hematopoietic progenitors or in vivo on the capacity of
      marrow reconstituting function in patients treated with myeloablative cancer
      therapy and autologous blood cell transplant. Oxypolygelatine is commercially
      available for clinical use as a plasma expander, is 30-fold less expensive than
      human serum albumin, is certified free of foreign serum proteins and antibodies
      as well as free of pyrogen, viral, mycoplasmal and bovine spongiform
      encephalopathy contaminants. Because of these characteristics, oxypolygelatine
      permits avoidance of: (1) the use of expensive serum albumin; (2) the fastidious
      preparation of autologous plasma or serum, and (3) the risk of infection
      associated with the infusion of allogeneic serum. Because of these practical
      advantages, we recommend the clinical use of oxypolygelatine as a substitute for
      human serum proteins for the routine cryopreservation of blood cell transplants.

PMID- 8879628
TI  - Synergy between lysosomotropic amines and cyclosporin A on human T cell responses
      to an exogenous protein antigen, tetanus toxoid.
AB  - Previously, it has been shown that the lysosomotropic amine, chloroquine, is
      effective in the prevention of graft-versus-host disease (GVHD) using murine
      models. Because chloroquine and hydroxychloroquine suppress MHC class II antigen
      presentation, their mechanism of action is different to other immune suppressant
      drugs (cyclosporin A) currently used to control GVHD. It is possible that the use
      of cyclosporin A and chloroquine in combination may have an additive or
      synergistic effect on T cell responses to antigens presented in the context of
      MHC class II. We investigated the effects of chloroquine or hydroxychloroquine in
      combination with cyclosporin A on human T cell responses in vitro to tetanus
      toxoid, an exogenous protein antigen dependent on MHC class II presentation for
      proliferative responses. We demonstrate that similar levels of chloroquine and
      hydroxychloroquine suppress human T cell responses to tetanus toxoid and that the
      use of either agent in combination with cyclosporin A results in synergistic
      suppression. Evaluation for a direct effect by the lysosomotropic amines on T
      cells, in the absence of antigen presenting cells, revealed that there was
      inhibition of T cell responses but only at high concentrations. No significant
      decrease or increase was seen in surface MHC II or invariant chain expression or
      in cytoplasmic invariant chain after exposure to chloroquine. Thus,
      lysosomotropic amines in combination with cyclosporin A are synergistic in
      suppression of T cell proliferation. Use of these agents in combination with
      cyclosporin A may improve control of graft-versus-host disease.

PMID- 8879629
TI  - Treatment of hepatic veno-occlusive disease with low-dose tissue plasminogen
      activator: impact on coagulation profile.
AB  - An 18-year-old white male developed severe hepatic veno-occlusive disease (VOD)
      during an autologous bone marrow transplant for primary refractory nodular
      sclerosing Hodgkin's disease. As a result of VOD-induced hepatic dysfunction,
      coagulation studies revealed depression of vitamin K dependent procoagulant
      factor VII. Intravenous recombinant tissue plasminogen activator 20 mg over h on
      4 consecutive days and continuous heparin infusion (1000 unit bolus followed by
      150 units/kg/day) resulted in rapid reversal of the VOD syndrome. During
      treatment, procoagulant factors II, VII, IX and X levels increased indicating the
      return of hepatic synthesizing capacity. Factor V levels, which were elevated pre
      therapy, also rose dramatically. Plasma antigen levels of protein C, a natural
      anticoagulant, remained severely depressed. No clinical evidence of bleeding and
      only minimal systemic fibrinolysis was noted. Despite concerns regarding the use
      of lytic therapy in a thrombocytopenic post-BMT patient, serial measurements of
      coagulation parameters during severe VOD suggested that low dose rt-PA improved
      portions of the systemic hemostatic profile.

PMID- 8879631
TI  - Successful use of topical retinoic acid in severe dry eye due to chronic graft
      versus-host disease.
AB  - Topical retinoic acid has proved to be of variable benefit in a number of dry eye
      disorders of disparate aetiology, in which squamous metaplasia with
      keratinization of ocular epithelium is present. Its exact role in patients with
      dry eye however remains in dispute. We describe a case of severe dry eye due to
      chronic graft-versus-host disease, which was refractory to conventional therapy
      but which responded remarkably to topical retinoic acid with reversal of
      conjunctival keratinization and marked resolution of symptoms.

PMID- 8879630
TI  - Evidence of induced non-tolerance in HLA-identical twins with hemoglobinopathy
      after in utero fetal transplantation.
AB  - Fetus-to-fetus transplantation has been suggested for the treatment of
      hemoglobinopathies in utero. However, dissimilar results have to date been
      obtained by different groups. We describe a case in which fetus-to-fetus
      transplantation in HLA-identical twins was performed at the 19th week of
      gestation by infusion of 0.8 ml of fetal blood from normal to beta-thalassemia
      affected fetus with the main aim of inducing tolerance. No evidence of
      engraftment, determined by KM19 polymorphism, was present after 2 years of the
      procedure. Moreover, an alloreactive cytotoxic T lymphocyte precursor (CTLp)
      study of affected fetus vs donor and other different stimulators showed that
      immunization vs tolerance was the real effect of the procedure.

PMID- 8879632
TI  - Transjugular intrahepatic portosystemic shunting (TIPS) for treatment of severe
      hepatic veno-occlusive disease.
AB  - Severe veno-occlusive disease (VOD) of the liver is a frequent cause of morbidity
      and mortality in patients undergoing transplantation. While surgical
      portosystemic shunts have been reported to be useful in the treatment of severe
      hepatic VOD with intractable ascites, few of these patients are surgical
      candidates. We report a case of severe VOD after autologous peripheral blood
      progenitor cell transplantation treated with transjugular intrahepatic
      portosystemic shunting (TIPS). This procedure resulted in marked improvement in
      the patient's ascites, coagulation status and urinary output. The safety and
      efficacy of this non-surgical approach for the treatment of patients with severe
      VOD requires prospective studies.

PMID- 8879633
TI  - Successful donor leukocyte infusion for chronic myeloid leukemia relapsing in
      accelerated phase after T cell-replete unrelated marrow transplantation.
AB  - A 47-year-old man relapsed with accelerated phase CML 19 months after a T cell
      replete unrelated BMT. Three donor leukocyte infusions (DLI) from the original
      donor resulted in durable complete hematological and cytogenetic remission.
      Moderate GVHD developed but was steroid responsive. This report suggests that DLI
      can be administered safely to patients relapsing after unmodified unrelated
      allografts. In the patient described, DLI exerted an antileukemic effect
      sufficiently potent to reverse accelerated phase disease.

PMID- 8879634
TI  - Parkinsonism during cyclosporine treatment.
AB  - Cyclosporine has been associated with various neurological side-effects including
      postural tremor, seizures, headaches, encephalopathy, cortical blindness, and
      visual hallucinations. We describe here two patients who developed parkinsonism,
      with rest tremor and bradykinesia, after receiving cyclosporin A following
      allogeneic bone marrow transplantation. The patients did not have pre-existing
      neurological disorders, and had not received significant amounts of dopamine
      blocking drugs. One patient improved markedly with Sinemet (carbidopa-levodopa),
      while the other (who did not tolerate Sinemet) improved with decrease in
      cyclosporine dosage. The relation of the parkinsonian symptoms to cyclosporine
      therapy and lack of other evident causes for the symptoms, suggests that
      parkinsonism may be an occasional consequence of cyclosporine.

PMID- 8879635
TI  - Secondary migration: a complication of Hickman central venous catheters.
AB  - We report two patients with spontaneous intrajugular migration of Hickman
      catheters which were initially correctly placed with the tip in the right atrium,
      via the right subclavian vein. In one patient the catheter remained in situ for
      40 days without any sequelae; in the second patient the catheter was removed
      immediately. In the first patient two interim chest radiographs disclosed the
      catheter's course suggesting a possible mechanism of migration. Since early
      detection of this complication allows interventional repositioning, periodic
      monitoring of indwelling catheters by chest X-ray is recommended.

PMID- 8879636
TI  - G-CSF stimulation of donor myelopoiesis prolongs survival of relapsed BCR-ABL
      positive acute lymphoblastic leukemia after allogeneic marrow transplantation.
AB  - An allogeneic sex-mismatched BMT which was performed in a male patient with BCR
      ABL-positive ALL in second hematological and central nervous system relapse
      resulted in a CR for 12 months. After BMT, the patient was closely monitored with
      reverse transcription (RT)-PCR. One month before a third relapse RT-PCR became
      positive. During relapse G-CSF was administered. It specifically stimulated the
      donor-derived myelopoiesis and led to the stabilization of the disease for 8
      months. Fluorescence in situ hybridization analyses of individual cell
      populations revealed that during the whole course of G-CSF administration
      granulocytes, CD4+, CD8+ and CD34+/CD10- cells were of female (donor) origin and
      only the CD34+/CD10+ cells which represented the leukemic blasts, were of male
      (host) origin.

PMID- 8879637
TI  - Progressive autologous graft-versus-host disease induced by cyclosporin A.
AB  - The development of graft-versus-host disease (GVHD) in patients undergoing
      allogeneic bone marrow transplantation for leukemias and lymphomas has been
      associated with a lower incidence of relapse. This phenomenon is thought to be
      secondary to the anti-tumor effect of adoptively transferred cells. Cyclosporin A
      (CsA) therapy is known to cause autologous and syngeneic GVHD in experimental
      models and humans, and has been used in patients undergoing autologous bone
      marrow transplantation. It has been the consensus to date that CsA-induced
      autologous GVHD is generally mild, confined to the skin, self-limiting and non
      life-threatening. We report by case of severe and progressive GVHD induced by CsA
      in a child following autologous bone marrow transplantation for acute
      lymphoblastic leukemia in second remission.

PMID- 8879638
TI  - Successful treatment of primary extramedullary leukemia (EML) of the uterus with
      radical surgery, chemotherapy, autologous bone marrow transplantation (BMT) and
      prophylactic local irradiation.
AB  - Extramedullary myeloid cell tumors are rare manifestations of acute
      nonlymphocytic leukemia (ANLL). While many advances in diagnosis have been made,
      dilemmas remain concerning the treatment of this disease. In primary
      extramedullary leukemia (EML) most reports agree upon a local therapy followed by
      systemic chemotherapy such as is used for ANLL. However, further prophylactic
      local or systemic therapy with stem cell support remains controversial. A 20-year
      old patient was diagnosed as having granulocytic sarcoma (GS) of the uterus
      without evidence of ANLL in 1991. After resection of the tumor at the uterine
      cervix and chemotherapy with daunorubicin 50 mg/m2 (days 1-3) and cytosine
      arabinoside 200 mg/m2 (days 1-7) in September 1991, complete remission was
      achieved. In October 1991 cytosine-arabinoside 1000 mg/m2 every 12 h from day 1
      to day 6 and amsacrine 200 mg from day 5 to day 7 were given as consolidation.
      Two years later relapse occurred in the adnexae. After radical hysterectomy, the
      same induction and consolidation chemotherapy was administrated. Subsequently,
      cytoxane 60 mg/m2 and fractionated total body irradiation (6 x 200 cGy) were
      given as conditioning and the previously cryopreserved bone marrow was reinfused.
      Finally, after hematopoietic engraftment, prophylactic local irradiation (4500
      cGy) to the pelvis was given resulting in a disease-free long-term survival of
      more than 36 months after relapse. Although this experience is confined to one
      patient, it may contribute to the design of prospective therapeutic studies in
      patients with primary EML.

PMID- 8879639
TI  - Successful allogeneic bone marrow transplantation for early relapse after
      autologous bone marrow transplantation in two cases of aggressive high-grade non
      Hodgkin's lymphoma.
AB  - Two patients with high-grade disseminated non-Hodgkin's lymphoma relapsed 3 and 7
      months respectively after high-dose chemotherapy and autologous BMT performed in
      first complete remission. Both patients had an HLA-identical sibling and received
      an allogeneic BMT 5 and 10 months after autologous BMT, after conditioning with
      fractionated 12 Gy total body irradiation plus cyclophosphamide. They both are
      alive and well, with a Karnofsky score of 100%, 15 and 27 months after allogeneic
      BMT. For selected patients with HLA-identical siblings and good performance
      status who relapse after autologous transplantation for high-grade non-Hodgkin's
      lymphoma, allogeneic BMT may be an option.

PMID- 8879640
TI  - Graft-versus-leukemia effect after allogeneic bone marrow transplantation for
      chronic lymphocytic leukemia.
AB  - We report the case of a patient with chronic lymphocytic leukemia (CLL) with
      persistent lymphocytosis and lymphadenopathy after allogeneic bone marrow
      transplantation (BMT). After receiving a donor lymphocyte infusion on day 87 he
      achieved complete remission upon development of chronic graft-versus-host
      disease, suggesting that a graft-versus-leukemia effect is operative in this
      malignancy.

PMID- 8879641
TI  - Changes in reticulocyte fractions during peripheral stem cell harvesting
      exclusively mobilized with rhG-CSF.

PMID- 8879642
TI  - Some semantic considerations on bone marrow transplantation.

PMID- 8879643
TI  - Reflex sympathetic dystrophy.
AB  - Reflex sympathetic dystrophy presents with pain out of proportion to the cause,
      loss of function, and significant evidence of an autonomic disorder. These
      findings are often accompanied by psychological disturbances, which can dominate
      the condition. There are differences in the symptoms and signs during childhood.
      It is more frequent among girls than boys, and the legs are more often affected
      than the arms; and trophic changes may be absent. There may be no history of
      trauma, and the response to treatment is often satisfactory. There are a number
      of theories on etiology. A disorder of the sympathetic nervous system with
      increased activity has been suggested, but on the evidence available super
      sensitivity to neurotransmitters is more likely. Also there may be a spinal, as
      well as a peripheral, component to the sensitivity. Other suggestions include the
      release of a pain substance, a disturbance of natural opioid metabolism, and an
      exaggerated inflammatory response. The diagnosis is mainly clinical, supported by
      X-ray examination, bone scans with Technetium 99m labelled diphosphonates, and a
      characteristic scintograph pattern. Laser Doppler flowmetry can also, be useful.
      The most effective preventative measure is control of pain and early
      mobilisation. Many treatments have been tried, but the response is variable.
      Drugs include analgesics, non-steroid anti-inflammatory drugs, anti-depressants,
      and steroids. Betablockers, with gradually increasing doses may help; as may
      vasodilators. Calcitonin, by intramuscular injection has been given a
      particularly favourable report. Physiotherapy is of prime importance. Some
      treatments are only likely to be considered in older children. Blocking of
      sympathetic pathways can be tried with paravertebral or epidural injections of
      local anesthetics. Regional intravenous injections of alpha adrenergic blocking
      agents distal to a tourniquet can relieve pain, but usually only transiently; and
      ketanserin may act favourably as a serotonin antagonist. Surgical sympathectomy
      can also be considered.

PMID- 8879644
TI  - Vascular involvement in benign infantile mitochondrial myopathy caused by
      reversible cytochrome c oxidase deficiency.
AB  - A 1-month-old Japanese girl had profound generalized weakness, hypotonia, and
      severe lactic acidosis. The infant improved gradually: she held her head at 9
      months, learned to walk by 15 months. At the first muscle biopsy at 11 weeks of
      age, the specimen was characterized by numerous ragged-red fibers and decreased
      enzyme activity on cytochrome c oxidase (COX) staining. Electron microscopic
      findings were characterized by the presence of excessive abnormal mitochondria
      not only in skeletal muscle fibers but also in blood vessels. Vascular
      abnormalities consisted of an increased number of enlarged mitochondria in
      endothelial and smooth muscle cells of small arteries. Biochemical analysis
      showed an isolated defect of COX activity, which was only 16% of the mean control
      level. At the second biopsy at 44 months of age, the COX activity had increased
      to normal in the entire specimen. On electron microscopy, the abnormal
      mitochondria present on the first biopsy specimen had disappeared both in muscle
      fibers and blood vessels; nearly all mitochondria were morphologically normal at
      the second biopsy. Now at 5 years of age she can run and does not show muscle
      weakness. We report reversibility of abnormal mitochondria with age not only in
      skeletal muscle fibers but also in blood vessels in a patient, who had reversible
      COX deficiency with a benign clinical course.

PMID- 8879645
TI  - Neuronal migrational disorders in children with epilepsy: MRI, interictal SPECT
      and EEG comparisons.
AB  - Single-photon emission computed tomography (SPECT) is being increasingly used in
      the investigation of children with epilepsy and may provide insights into
      congenital malformations. We analyzed the interictal 99Tc-HMPAO-SPECT in a series
      of seven children with developmental disorders of the neocortex, each of them
      representing a prototype of cerebral dysgenesis, such as lissencephaly,
      pachygyria, opercular dysplasia, polymicrogyria, nodular heterotopia and band
      heterotopia. The patients studied were selected among 22 epileptic children with
      neuronal migrational disorders (NMDs). Interictal SPECT hypoperfusion was
      observed in the area homologous to MRI findings in all the examined children. In
      three patients low perfusion was also present in the opposite hemisphere,
      probably due to functional involvement or related to an underlying
      microdysgenesis, not revealed by structural imaging. EEG features were in
      agreement with low perfusion areas, both anatomically and functionally, in all
      children. In one patient hypoperfusion area differed from that revealed by MRI
      and EEG. Ictal SPECT has been considered a useful tool for accurately locating
      the epileptic focus. Nevertheless, interictal brain perfusion studies, together
      with proton magnetic resonance spectroscopy, may play an important role in
      detecting anatomic substrate in developmental disorders of the neocortex.

PMID- 8879646
TI  - Relation of early neuromotor and cranial signs with neuropsychological outcome at
      4 years.
AB  - The persistence and predictive value at 3-5 years of age of three signs detected
      within the first 18 months of life were investigated: phasic stretch reflex in
      one or both gastrocnemius muscles, imbalance in passive axial tone with an excess
      of dorsal extension, and a ridge on the squamous sutures. Phasic stretch reflex
      and at least one of the other signs were found in 14 children during repeated
      assessments within the first 18 months. The progress of these children was
      compared with that of 14 matched controls who had repeatedly normal neurological
      assessments during the first 18 months in the same clinic in Paris. At the age 3
      5 years all the children were then assessed blindly by the second author from a
      pediatric neurological viewpoint and by two psychologists and two psychomotor
      therapists as well. The parents of the affected children reported significantly
      more problems in motor/praxis skills, language development and attention.
      Abnormal neurological signs were also significantly more frequent than in the
      controls. Suboptimal cognition did not reach significance. The neurological
      inclusion criteria were still present at 3-5 years old in 86% (vs. respectively
      100% and 93% during the first 18 months of life) of this small group of children,
      while the cranial suture sign was still present in only 28% (vs. 64%). Findings
      of these three signs during the first 18 months of life may help in predicting
      long-term neurobehavioral or long-term neuropsychological problems.

PMID- 8879647
TI  - Type of initial brainstem auditory evoked potentials (BAEP) impairment and risk
      factors in premature infants.
AB  - Brainstem auditory evoked potentials (BAEPs) were recorded in 89 premature
      infants aged between 34 and 52 weeks. 47.2% had normal and 52.8% abnormal BAEPs
      in at least one ear. Seven risk factors were taken into account: birth weight
      lower than 1500 g, hypoxia, neurological damage, fetal pathology, associated
      malformation, the use of ototoxic drugs, and exchange transfusion. The type of
      BAEP impairment was defined as either endocochlear, transmission or retrocochlear
      damage. Percentage BAEP impairment was higher in case of hypoxia (63.3%) but
      remained similar whether the other risk factors were present or absent.
      Transmission impairment was more frequent in case of birth weight lower than 1500
      g, hypoxia or ototoxic drug administration; Endocochlear damage occurred more
      frequently when ototoxic drugs had been used or exchange transfusion performed.
      When birth weight was lower than 1500 g, transmission damage was more frequent
      than when birth weight was higher than 1500 g. In contrast, endocochlear damage
      was more frequent when birth weight was higher than compared with lower than 1500
      g. In male infants, BAEP impairment was more frequent and more often of
      retrocochlear type than in female infants. BAEP impairment was more frequently of
      endocochlear type in female compared to male infants. Among the 89 premature
      infants recorded, 11.2% has endocochlear damage corresponding to potentially
      handicapping hearing loss. These results are discussed with reference to the
      literature.

PMID- 8879648
TI  - Cortical somatosensory evoked potentials to posterior tibial nerve stimulation in
      newborn infants.
AB  - Successful cortical recordings of somatosensory-evoked potentials (SEPs) to
      posterior tibial nerve (PTN) stimulation were obtained in 21 (87.5%) for P1 and
      22 (91.7%) for N1 of 24 infants who were followed up for at least 3 years and had
      a normal outcome. There were linear decreases with increasing post menstrual age
      in both P1 and N1 peak latency. Of the four cases with diplegia later, three
      showed definite abnormalities, no responses and delayed latency in PTN SEPs
      respectively, however, the other case showed normal responses. Of the three cases
      with mental retardation, two showed relatively long latency and borderline
      responses respectively, and the other case showed normal responses. As the
      pathway of PTN SEPs traverses the periventricular area of the brain likely to be
      affected by ischemic lesions in premature infants, abnormalities in the responses
      might indicate a later motor disorder.

PMID- 8879649
TI  - Muscle histopathology in spastic cerebral palsy.
AB  - We studied the histopathology of spastic muscles in patients with spastic
      cerebral palsy using specimens obtained from the gastrocnemius muscles during
      orthopedic operations. Though there was no disease-specific abnormality, we found
      changes in fiber type distribution, i.e., type-1 fiber predominance and type-2B
      fiber deficiency. These changes were not found in the patient with brain
      infarction at age 1 year 5 months. Variation in fiber size, especially in type-1
      fibers, was also detected in older patients and at the more severely affected
      sides. We speculated that the influence on the spinal motor unit from upper motor
      cortex might be applicable to the muscle histological findings and the time of
      the onset of the brain damage might be important.

PMID- 8879650
TI  - Sensorineural deafness in siblings with adenosine deaminase deficiency.
AB  - Two siblings with adenosine deaminase deficiency were successfully treated with
      allogeneic bone marrow transplantation without conditioning. Although the
      patients were free from infections after immunologic reconstitution, both showed
      sensorineural deafness at 1 year of age. Because there were no structural
      abnormalities in the inner and middle ears, no evidence of prenatal infections of
      rubella, cytomegalovirus or toxoplasma, and no postnatal infection of mumps in
      the siblings, sensorineural deafness might be one of the neurologic problems
      associated with adenosine deaminase deficiency.

PMID- 8879651
TI  - A cloverleaf skull syndrome probably of Beare-Stevenson type associated with
      Chiari malformation.
AB  - A case of cloverleaf skull (CLS) syndrome with Chiari malformation was reported.
      The patient developed congenital hydrocephalus, upper airway obstruction and
      breath holding spells. Ventriculo-peritoneal shunt improved the hydrocephalus,
      but the patient progressively developed apneic episodes in spite of intubation.
      Brain magnetic resonance imaging (MRI) disclosed severe Chiari malformation.
      Laminectomy of the cervical vertebrae and craniectomy at the occipital bone were
      performed to relieve the brain stem compression. Postoperatively, the respiratory
      symptoms improved slightly, but 8 weeks later the patient suddenly died.
      Literature survey revealed that this is the second case report of CLS associated
      with Chiari malformation. It was assumed that the respiratory problems in our
      patient are ascribable to the Chiari malformation as well as the upper airway
      obstruction. The patient here reported seems to be a case of Beare-Stevenson
      cutis gyrata syndrome, in view of an association of multiple characteristic
      dysmorphic features, in addition to CLS.

PMID- 8879652
TI  - Macrocephaly and chromosome disorders: a case report.
AB  - We report the case of a young patient with macrocephaly. After excluding the most
      frequent causes of macrocephaly (hereditary disorders, degenerative, osseous and
      metabolic diseases, neurocutaneous syndromes and cerebral malformations), the
      likelihood of a chromosome disorder was investigated, revealing an unbalanced de
      novo translocation: 46,X,der(X),t(X;7) (q13 or q13.2; q11.23 or q21.11), i.e., a
      partial trisomy of the long arm of chromosome 7, associated with a partial
      monosomy of the long arm of chromosome X. Though this chromosome disorder is
      relatively rare, it should be considered in the differential diagnosis of
      patients under one year of age presenting with macrocephaly, scoliosis and non
      progressive psychomotor retardation.

PMID- 8879653
TI  - Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic
      spasms and focal cortical dysplasia. Report of three Italian cases in two
      families.
AB  - We report clinical, EEG and neuroimaging findings of three patients in two
      Italian families with merosin-negative congenital muscular dystrophy (CMD), drug
      resistant occipital epilepsy, diffuse persistent cerebral white matter changes
      and focal cortical dysplasia. Clinical and epilepsy histories, EEG and
      neuroimaging findings were very similar in all patients. Seizures started in
      childhood and mainly consisted of periodic spasms, a particular type of partial
      seizure characterized by clusters of epileptic spasms. The motor expression of
      the spasms was very mild so that they had been frequently missed or
      misinterpreted as non-convulsive generalized absence seizures. Interictal EEG
      showed occipital spike-waves and bilateral synchronous slow spike-wave
      discharges. Ictal EEG showed prolonged periodic sequences of slow waves with
      associated fast rhythm complexes, characteristic of periodic spasms. Two patients
      had normal intelligence, one patient presented moderate mental retardation. Focal
      cortical dysplasia in the posterior areas of the brain, in addition to marked
      diffuse white matter alterations, was detected in the magnetic resonance images
      of all patients. Findings in these patients indicate that in merosin-negative CMD
      brain involvement can include cortical dysplasia, in addition to white matter
      changes. In such cases the brain damage can lead to a childhood-onset
      localization-related symptomatic occipital epilepsy. Epileptic seizures and
      cortical dysplasia can be, however, difficult to detect in CMD. The clinical
      semiology of epileptic seizures may in fact be modified because of muscular
      weakness. This implies that epilepsy may be misdiagnosed or even missed and EEG
      polymyographic recordings may be necessary to identify it. Similarly, cortical
      dysplasia may be very localized and visible by neuroimaging only if it is
      carefully investigated on the basis of epileptological and EEG-polymyographic
      findings.

PMID- 8879654
TI  - Merosin positive congenital muscular dystrophy with severe involvement of the
      central nervous system.
AB  - Congenital muscular dystrophy (CMD) is one of the most frequent dystrophies of
      childhood, which is commonly characterized by neonatal muscle impairment with or
      without clinical evidence of central nervous system involvement. Several variants
      of CMD have been described and the disease has recently been classified into five
      clinically distinct forms: the two classical CMDs with and without deficit of the
      laminin M chain (merosin), the Fukuyama CMD described in Japanese patients and
      recently linked to the chromosome 9q31-33, the clinically more severe Walker
      Warburg syndrome and the rare muscle-eye-brain disease described in Finnish
      patients. The most of these forms have central nervous system involvement. This
      is usually not seen in the classical merosin positive CMD, but can be very severe
      in the others. Here we describe a 3-year-old Mediterranean child with clinical
      and histopathological signs of CMD, normal expression of merosin, severe clinical
      and radiological evidence of central nervous system involvement without defects
      of neuronal migration or brain malformations and without ocular anomalies. This
      report suggests that new forms of CMD and cerebral involvement can still be
      recognized and confirms the heterogeneity of this group of infantile diseases.

PMID- 8879656
TI  - Intracranial hypertension and cryptococcal meningitis in a girl with AIDS.
AB  - A girl with HIV infection acquired at birth by blood transfusion, was admitted at
      the age of 10 years for diplopia, vomiting, headache and papilledema. CT scan was
      negative. A lumbar puncture revealed clear CSF, protein 0.40 g/l, glucose 2
      mmol/l, 5 mononuclear cells/mm3. The Indian ink preparation and the latex
      agglutination antigen test were positive for Cryptococcus n. Treatment with
      amphotericin B and flucytosine was started. After 10 days, since the in vitro
      susceptibility testing of the isolates showed resistence to both drugs,
      fluconazolo (400 mg/day) was started. Acetazolamide, furosemide and
      spironolactone were then added to the antifungal therapy for the persistence of
      severe intracranial hypertension. Diuretics were maintained for 10 weeks. The
      patient returned to school two and half months after the admission to the
      hospital. After 19 months, she is doing well and she is on maintenance of
      fluconazole (200 mg/day). We hypothesized that the increased intracranial
      pressure would be due to an impaired CSF reabsorption probably as a consequence
      of a direct cryptococcal infiltration of the villi.

PMID- 8879655
TI  - Transcranial magnetic stimulation in an adrenoleukodystrophy patient.
AB  - We experienced an 11-year-old boy diagnosed as having adrenoleukodystrophy (ALD),
      and studied his motor evoked potentials (MEPs) elicited by transcranial magnetic
      stimulation (TMS). He had intellectual and visual impairment, and MRI revealed
      high intensity of the parieto-occipital white matter. On evaluation of the long
      tracts, slight spasticity with equivocal Babinski signs was noted: however, the
      long tracts appeared intact on MRI, and short latency somatosensory evoked
      potentials (SSEPs) were completely normal. On TMS delivered through a circular
      coil, MEPs recorded from the relaxed first dorsal interosseous muscle showed that
      only the duration was significantly prolonged, which may be due to temporal
      dispersion of descending volleys in the pyramidal tracts, while the latency was
      not prolonged. TMS in ALD was considered sensitive and useful for detecting
      subtle involvement of the long tracts.

PMID- 8879657
TI  - Child neurology in Lithuania: past, present and future.

PMID- 8879658
TI  - Child neurology in Latvia.

PMID- 8879659
TI  - Pediatric neurology in Estonia.

PMID- 8879660
TI  - Report on the 3rd conference of the Baltic Child Neurology Association, Palanga,
      Lithuania, May 21-24, 1995.

PMID- 8879661
TI  - Head injury and sexual dysfunction.
AB  - An extensive review of the head injury and human sexuality literature was
      completed, to augment an understanding of the impact of traumatic head injury on
      sexual functioning. Despite clinical evidence that sexual dysfunction after head
      injury is prevalent and of great import, sexual concerns have been neglected in
      much of the post-traumatic head injury and rehabilitation literature.
      Characteristics of head injury concerning cerebral physiology, post-traumatic
      sequelae, and the effects on sexual functioning are examined. Rehabilitation and
      family/spouse literature was also examined for information on sexuality. The
      majority of this article reviews research on sexual sequelae after head injury,
      such as impulsiveness/inappropriateness, changes in libido and sexual frequency,
      global sexual difficulties, and specific sexual dysfunctions. Treatment models
      for the sexual problems after head injury are also reviewed and found to be
      limited in number. Treatment issues and suggestions are addressed. This article
      provides information about the sexual problems of head-injured patients to
      facilitate the development of diagnostic and intervention programmes.

PMID- 8879662
TI  - Sexual functioning following traumatic brain injury.
AB  - In this study we investigated sexual functioning in 52 outpatients with a history
      of traumatic brain injury to determine: (1) the prevalence of reported sexual
      dysfunction; and (2) the relationship between sexual functioning and age,
      severity and locus of injury, time since injury, and physical and cognitive
      function. Reports of sexual functioning indicated a reduction below levels within
      non-injured populations, but only to statistically significant levels on two
      scales of the Derogatis Interview of Sexual Function (DISF): Orgasm and
      Drive/Desire. Location of injury was related to sexuality in that patients with
      frontal lobe lesions reported an overall higher level of sexual satisfaction and
      functioning than those individuals without frontal lobe lesions. Time since
      injury was inversely related to reports of levels of sexual arousal; that is,
      patients with more recent injuries reported greater levels of arousal than those
      not recently injured. Right hemisphere injuries also correlated with higher
      scores on reports of sexual arousal and sexual experiences.

PMID- 8879663
TI  - High-level linguistic disturbances subsequent to childhood closed head injury.
AB  - High-level language functioning was assessed in a group of 11 children with
      severe closed head injury (CHI). Performance was examined on measures of
      figurative language, oral expression, inferencing, and interpretation of
      ambiguous sentences, and was compared with that of a control group matched for
      age, gender, and handedness. The children with CHI demonstrated inferior
      performance on the oral expression, ambiguous sentences, and figurative language
      tests; however, performance on the inferencing task appeared intact. These
      findings are discussed with respect to the underlying nature of the observed
      impairments. Both linguistic and cognitive factors are considered. It is
      concluded that a complex interaction of cognitive and linguistic impairments
      experienced by children with CHI may underlie the performance deficits identified
      in the current study.

PMID- 8879664
TI  - Episodic symptoms in dysfunctioning children and adolescents following mild and
      severe traumatic brain injury.
AB  - The present investigation examines the phenomenology of episodic symptoms in
      dysfunctioning children and adolescents following mild (n = 25) or severe (n =
      25) traumatic brain injury (TBI). TBI patients in both groups commonly endorsed
      symptoms such as staring spells, memory gaps, and temper outbursts.
      Anticonvulsant response in the 27 patients treated, reflected moderate to
      substantial improvement in 92%. A dose-response relationship between injury
      severity and number of episodic symptoms was not observed; however, patients in
      the severe TBI sample did produce significantly more defective performances on a
      dichotic word-listening task (DWLT) and lower IQ values. Defective DWLT
      performance was also significantly associated with greater number of episodic
      symptoms endorsed, but only in the mild TBI sample. Parallels with epilepsy
      spectrum disorder and clinical implications for paediatric TBI are discussed.

PMID- 8879665
TI  - Post-traumatic stress disorder following minor and severe closed head injury: 10
      single cases.
AB  - Post-traumatic stress disorder (PTSD) was found to occur after minor or severe
      closed head injury in 10 single cases which are reported in detail. They were
      drawn from 312 cases of closed head injury who were referred for
      neuropsychological assessment or neurorehabilitation. All cases which had been
      given both diagnoses are presented. Information was collected retrospectively
      from case notes and reports. It is argued that a continuum of experience, which
      represents the entirety of an event, is not necessary for PTSD to occur, but that
      a "window' of real or imagined experience which results from loss of
      consciousness and post-traumatic amnesia after closed head injury need not
      prevent the symptoms of PTSD from arising, although they may make them less
      likely and the phenomenon of the dual diagnoses relatively rare. The issue of
      whether PTSD found following closed head injury is a subclassification of PTSD is
      raised.

PMID- 8879666
TI  - Air embolism in the agitated traumatic brain injury patient: an unusual
      complication.
AB  - Central venous catheters are often utilized in the acute care management of the
      traumatic brain injury (TBI) patient. While in the agitated phase of recovery,
      TBI patients often focus on removing indwelling tubes or venous access lines. Air
      embolism is among the most serious complications reported in the use of central
      venous catheters. We present a case of air embolism in an agitated patient, and
      discuss prevention methodologies. A 38-year-old male was involved in a fall, with
      an initial Glasgow Coma Scale of 12. CAT scan imaging revealed a left frontal
      intracerebral haematoma. He required central venous catheter placement for
      management of associated chest and abdominal injuries. Agitated from early in his
      stay, the patient was able to twist off several hubs from the central venous
      catheter with his teeth, resulting in an air embolus. The patient experienced
      sudden clinical deterioration with oxygen saturation decling to 70%. The
      patient's course improved after several days of ventilatory support. He
      eventually successfully completed inpatient rehabilitation, achieving
      independence in activities of daily living and ambulation. This case illustrates
      a serious potential complication in the agitated patient. Physicians and
      rehabilitation specialists should advocate for secured taping of central venous
      catheter hubs and adequate padding of catheter dressings in agitated patients.

PMID- 8879667
TI  - Road to awareness: an individualized training package for increasing knowledge
      and comprehension of personal deficits in persons with acquired brain injury.
AB  - Research suggests that awareness of one's deficits may be a significant factor in
      the recovery process after acquired brain injuries (ABI). Various methods have
      been employed to teach awareness of the potential sequelae of ABI. The present
      study extended the use of a board game format to teach awareness to adults with
      ABI who exhibited serious unwanted behaviours. It used an individualized training
      package in conjunction with a game format in order to more specifically target
      individual client awareness of personal deficits in two areas: cognition and
      behaviour. Training focused on the first three levels within Bloom's Cognitive
      Taxonomy: knowledge, comprehension, and application. Components of both the
      multiple-baseline and multiple-probe design were used to demonstrate experimental
      control. All three participants responded favourably to training, as evidenced by
      increases in percentage of questions answered correctly during the game sessions
      and in pre/post-generalization probes in both cognitive and behavioural
      categories.

PMID- 8879668
TI  - Staff stress in head injury rehabilitation; Brain Injury, 10(2): 133-138.

PMID- 8879669
TI  - Neuronal mechanisms of two-dimensional orienting movements in the cat. I. A
      quantitative study of saccades and slow drifts produced in response to the
      electrical stimulation of the superior colliculus.
AB  - To evaluate the metrics of rapid eye movements caused by the activation of
      distinct collicular microzones, the superior colliculus (SC) was electrically
      stimulated in alert behaving cats while their heads were restrained. A
      quantitative study of electrically induced rapid eye movements demonstrated that
      their amplitude and direction depended on the intensity of stimulation, the
      electrode location, and the initial position of the eyes, while their duration
      depended on the intensity of stimulation. When detailed quantitative procedures
      are employed, properties of saccades produced in response to the electrical
      stimulation of the feline SC resemble those of saccades elicited in response to
      the electrical stimulation of a variety of primate brain areas. Besides saccades,
      electrical stimulation of the feline SC gave rise to slow drifts whose amplitude
      and direction was also influenced by the initial position of the eyes. Because
      their size depended on the frequency of stimulation and their time course
      reflected mechanical properties of the oculomotor plant, induced slow drifts
      could be due to a more or less direct projection of the SC onto extraocular
      motoneurons. A model that includes such a variety of connections between the SC
      and extraocular motoneurons is presented and is shown to produce realistic
      combinations of fast and slow eye movements when its input is a step function of
      time. The present findings support the notion that an orbital mechanical factor
      underlies the eye position sensitivity of slow drifts and saccades evoked in
      response to the electrical stimulation of the SC.

PMID- 8879670
TI  - Norepinephrine depletion in the amygdala inhibits CRF-41, ACTH, and
      corticosterone responses following photic simulation.
AB  - The effects of amygdaloid norepinephrine depletion by 6-hydroxydopamine on
      changes in corticotropin releasing factor-41 (CRF-41) and serum
      adrenocorticotropic hormone (ACTH) and corticosterone levels, following neural
      stimuli were investigated. In intact animals, photic or acoustic stimulation
      caused CRF-41 depletion from the median eminence and a rise in serum ACTH and
      corticosterone levels. In rats with amygdalar norepinephrine depletion there were
      no changes in basal CRF-41, ACTH, or corticosterone levels. However, the above
      responses of the hypothalamo-pituitary adrenocortical axis were blocked following
      photic, but not acoustic, stimulation. These results indicate that the
      facilitatory role of the amygdala on the above responses following photic
      stimulation depends on the presence of norepinephrine in this region.

PMID- 8879671
TI  - Norepinephrine levels in discrete brain nuclei in borderline hypertensive rats
      exposed to compound stressors.
AB  - The borderline hypertensive rat (BHR) appears to be an appropriate model for
      investigating the role of the environment in producing hypertension. Previous
      studies have demonstrated that the BHR shows chronic blood pressure elevations to
      both stress and high salt intake. Other studies suggest that interactions between
      the brain and kidney play an important role in initiating this hypertension. The
      central noradrenergic system has been implicated in these effects, especially in
      the hypothalamus. Because exercise has been found to attenuate stress-induced
      hypertension in the BHR, the current study sought to examine the impact of
      stressors paired with exercise (salt intake or stress) with those combining
      stress and high salt. Male BHR were exposed to either control, salt plus stress,
      salt plus exercise, or stress plus exercise conditions for either 2 or 6 months,
      beginning at 2 months of age. Following sacrifice, brain nuclei in the brain stem
      and hypothalamus were removed using the Palkovits micropunch technique. Punches
      were analyzed for NE content via liquid chromatography with electrochemical
      detection. Compared with the control condition, chronic salt plus stress led to
      reductions in NE content, especially in the hypothalamus. Compared with salt plus
      stress, the exercise conditions were associated with elevated NE levels,
      especially in the early phases of exposure to the treatment. The possible role of
      exercise training in preventing a central nervous system trigger from inducing
      hypertension in the BHR is discussed.

PMID- 8879672
TI  - Down-regulation of rat beta-adrenoceptors by clenbuterol or desipramine does not
      require chronic treatment: [3H] CGP-12177 binding reveals rapid (24 hour)
      modulation.
AB  - Desipramine (DMI, 15 mg/kg, s.c.) decreased [3H]CGP-12177-labelled cortical beta
      adrenoceptor density (Bmax) by 30% upon chronic (14 day) treatment. However, even
      a single dose (in mg/kg) of DMI (15) or the beta-adrenoceptor agonist,
      clenbuterol (20), induced a rapid (24 hour) and significant reduction of beta
      adrenoceptor Bmax (-15%; p < 0.01). Acute treatment with amitryptiline (10),
      clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no
      significant effect on [3H]CGP-12177-labelled beta-adrenoceptors, suggesting that
      rapid down-regulation may not be a general property of antidepressant drugs. None
      of the antidepressants altered the Bmax of [3H]ketanserin-labelled 5-HT2A
      receptors on acute treatment. These results show that beta-adrenoceptor down
      regulation by clenbuterol and DMI is not dependent on chronic treatment and may,
      therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen
      clinically with antidepressant drugs.

PMID- 8879673
TI  - Effects of centrally administered prostaglandin EP receptor agonists on febrile
      and adrenocortical responses in the prepubertal pig.
AB  - Febrile and adrenocortical responses to central (lateral ventricle) injections of
      prostaglandin E2 (PGE2) and E-series prostanoid receptor agonists (EP1, EP2, EP3,
      subtypes) were investigated in prepubertal pigs. In Experiment 1, administration
      of PGE2, (1.4, 5.6 nmol) produced dose-related increases in core temperature and
      plasma cortisol concentrations. In Experiment 2, approximately equimolar (1.2 to
      1.4 nmol) amounts of EP1, EP2, and EP2/EP3 agonists were compared. The EP2 and
      EP2/EP3 prostanoids raised core temperature, whereas the increase induced by the
      EP1 agonist was not significant. Similarly, although all of the agonists appeared
      to stimulate cortisol release, these results were also not significant. In
      Experiment 3, pigs treated with an EP3 agonist (1.3 nmol) showed marked febrile
      and adrenocortical responses. The results of these experiments are compared with
      data from the rat using the same agonists and route of administration. The
      findings are also discussed in relation to the distribution of receptor
      populations in vascular and synaptosomal compartments of the porcine brain.

PMID- 8879674
TI  - Sequential mediation of norepinephrine-and dopamine-induced antinociception at
      the spinal level: involvement of different local neuroactive substances.
AB  - The effects of intrathecally (i.t.) administered opioid antagonist naloxone
      (Nal), adenosine antagonist aminophylline (Aph), and gamma-aminobutyric acid
      (GABAA)-receptor antagonist picrotoxin (PTX) or Bicuculline (BIC) on the
      antinociception produced by i.t. norepinephrine (NE), dopamine (DA), morphine
      (Mor), 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine agonist) or muscimol
      (MUS, a selective GABAA-receptor agonist) were studied and compared using the
      tail-flick test in rats. The results showed that: (1) both i.t. NE (0.3, 0.5 and
      1.0 nmol) and DA (5.5, 8.3 and 16.5 nmol) produced significant and dose-dependent
      increases in tail-flick latencies (antinociception); (2) both Nal (240 nmol) and
      Aph (120 nmol) blocked the antinociception produced by NE (1.0 nmol); (3) both
      Nal (240 nmol) and Aph (120 nmol) blocked the antinociception produced by Mor
      (0.5 nmol), but only Aph (120 nmol) blocked the antinociception produced by NECA
      (0.5 nmol), while Nal (240 nmol) did not; (4) neither Nal (240 nmol) nor Aph (120
      nmol) altered the antinociception produced by DA (16.5 nmol); (5) both i.t. PTX
      (1.5 nmol) and BIC (0.5 nmol) completely blocked the antinociception produced by
      DA (16.5 nmol), but showed no effects on that produced by NE (1.0 nmol); and (6)
      both PTX and BIC blocked the antinociception produced by MUS (1.0 nmol). These
      results suggest that: (a) endogenous opiate and adenosine may be involved in the
      mediation of NE-induced, but not DA-induced, antinociception; (b) NE, opioid and
      adenosine may act in a sequential order in NE-induced antinociception at the
      spinal level; (c) endogenous GABA may be involved in the mediation of DA-induced
      antinociception through the GABAA-receptors, but is not involved in NE-induced
      antinociception at the spinal level.

PMID- 8879675
TI  - Lateral tegmental field neurons sensitive to muscular contraction: a role in
      pressor reflexes?
AB  - The medullary lateral tegmental field (LTF) has a major role in sympathetic nerve
      discharge (SND) rhythmicity, but its role in pressor reflexes generated by
      hindlimb muscular contraction (MC) is unknown. Therefore, two sets of experiments
      were performed in 17 chloralose-urethane anesthetized cats. First, responses of
      single LTF neurons to MC induced by L7-S1 ventral root stimulation were examined.
      The majority (30 of 47) of LTF neurons increased firing during MC. Most LTF
      neurons had a basal discharge correlated with the 2-10 Hz rhythm of SND or the
      cardiac cycle and responded to increases in blood pressure. Only seven neurons
      were inhibited by MC, most having a respiratory rhythm. Second, pressor responses
      to MC and to caudal hypothalamic stimulation were examined before and after
      bilateral LTF microinjections of a synaptic blocker (CoCl2) as well as with
      lidocaine. Microinjection of CoCl2 or lidocaine significantly attenuating the
      dominant 2-10 Hz power coefficient of SND had no effect on the pressor responses
      to MC or caudal hypothalamic stimulation. Therefore, LTF may be important for
      basal rhythms in SND and may help synchronize SND during MC, but its contribution
      to basal rhythms is apparently not required for pressor reflexes evoked by
      hindlimb MC or hypothalamic stimulation.

PMID- 8879676
TI  - Effects of the antiestrogen, RU 58668, on female sexual behavior in rats.
AB  - RU 58668 is a steroidal antiestrogen believed to be devoid of any partial agonist
      activity. Most of the work with RU 58668 has focused on its potential as an
      antineoplastic agent in the treatment of breast cancer, but it has not been
      tested for its effects on the brain and behavior. Other antiestrogens are
      problematic because most are either partial agonists or do not cross the blood
      brain barrier. The purpose of this study was to test if RU 58668 blocks two
      classic estrogen-dependent behaviors: female sexual behavior and feeding
      behavior. We used a repeated measures design to examine if RU 58668 reversibly
      blocked female sexual behavior. RU 58668 significantly reduced both the level of
      sexual receptivity and the level of proceptivity in a reversible manner. Changes
      in body and food weight were also measured. Our results show that RU 58668
      blocked estrogen's suppressive effects on feeding behavior and body weight.
      Therefore, RU 58668 is the first antiestrogen that blocks estradiol's effects on
      female sexual behavior while also inhibiting estradiol's effects on feeding
      behavior and body weight.

PMID- 8879677
TI  - Besipirdine (HP 749) reduces schedule-induced polydipsia in rats.
AB  - The aim of the present paper is to report on the adrenergic and serotonergic
      effects of besipirdine (HP 749) in vivo and to discuss its potential use in the
      treatment of obsessive compulsive disorder. Besipirdine inhibited biogenic amine
      uptake in vitro. It prevented tetrabenazine-induced ptosis in mice and
      potentiated the 5-hydroxytryptophan-induced serotonin syndrome in rats.
      Furthermore, it decreased schedule-induced polydipsic behavior in rats. Schedule
      induced polydipsia may be a model for obsessive compulsive disorder. Previous
      results from our group have shown that certain selective serotonin reuptake
      inhibitors decrease schedule-induced polydipsia after 14-21 days of treatment.
      Besipirdine reduced schedule-induced polydipsic behavior immediately and this
      reduction lasted throughout the duration of the experiment (29 days).

PMID- 8879678
TI  - Clinical surveillance for early stage breast cancer: an analysis of claims data.
AB  - This study estimates the costs of clinical follow-up for women with early stage
      breast cancer and evaluates the effects of patient and provider characteristics
      on follow-up intensity. Claims data were cumulated from 1/1/89 through 4/30/93
      for a comprehensive set of follow-up tests (office visits, radiologic, and
      laboratory) ordered for 222 women diagnosed at a university hospital between
      1/1/89 and 12/31/91. Aggregated measures of the volume and costs of follow-up
      over 6 month intervals were expressed in terms of Medicare's 1993 relative value
      units (RVUs) and their 1993 cost equivalents. Excluding the first 6 months, women
      received on average, 11.7 RVUs of follow-up in the first year (equivalent to a
      cost of $362), and 9.5 RVUs in the second year ($297). In the first year, chest x
      rays, clinical chemistry tests, automated hemograms, and bone scans, accounted
      for 36% of the cost of follow-up, while computerized tomographic scans and
      magnetic resonance imaging studies accounted for 30%. Multiple regression
      analysis of the first year data showed that women who received radiation and/or
      were followed by oncology, were more likely to receive intensive follow-up. Age,
      race, socioeconomic status, insurance, stage, and treatment did not impact follow
      up. Costs of follow-up for breast cancer are substantial, though much lower than
      suggested by others. Additionally, wide variations in practice are largely
      unexplained by patient and/or provider characteristics. In light of recent
      evidence questioning the benefit of intensive surveillance, this study supports
      the need for an accepted set of follow-up guidelines for breast cancer.

PMID- 8879679
TI  - Effect of a cytotoxic analog of LH-RH (T-98) on the growth of estrogen-dependent
      MXT mouse mammary cancers: correlations between growth characteristics and EGF
      receptor content of tumors.
AB  - Female BDF mice bearing estrogen-dependent MXT mouse mammary cancers were treated
      for 4 weeks with a cytotoxic analog of luteinizing hormone-releasing hormone (LH
      RH). T-98 (agonist [D-Lys6]LH-RH linked to glutaryl
      2(hydroxymethyl)anthraquinone). The effects of T-98 were compared to those of
      equimolar amounts of the cytotoxic moiety 2-(hydroxymethyl)anthraquinone
      hemiglutarate (G-HMAQ) and carrier LH-RH agonist [D-Lys6]LH-RH. Both T-98 and [D
      Lys6]LH-RH significantly inhibited the growth of MXT cancers, but G-HMAQ had only
      a minor non-significant effect. Cytotoxic analog T-98 and the carrier [D-Lys6]LH
      RH had similar inhibitory hormonal activities on the pituitary-gonadal axis, but
      T-98 caused a larger reduction in tumor volume and decreased proliferation
      characteristics such as mitotic activity and AgNOR numbers in tumor cells to a
      greater extent than the carrier. Tumor inhibition by T-98, [D-Lys6]LH-RH, and
      ovariectomy was connected with a significant decrease in binding capacity of EGF
      receptors in tumor cell membranes. The concentration of EGF receptors remained
      high in tumors that continued to enlarge in spite of treatment and in all control
      untreated tumors, even those of small size. Thus, the changes in EGF receptors
      are likely to be the result of the therapy. Treatment with T-98 caused a greater
      reduction in the binding capacity of EGF receptors in tumors than [D-Lys6]LH-RH.
      This could explain the higher inhibitory effect of the cytotoxic analog on tumor
      growth. Since radiolabeled T-98 was shown to accumulate in MXT cancers 3 hours
      after a subcutaneous injection, this indicates that specific targeting might play
      a role in the antitumor effect exerted by this cytotoxic analog.

PMID- 8879680
TI  - Activation of raf-1, MEK, and MAP kinase in prolactin responsive mammary cells.
AB  - The polypeptide hormone prolactin (Prl), acting through its cell surface
      receptors, promotes growth and differentiation in normal and malignant breast
      cells. We demonstrate herein that two Prl-responsive cell lines, NOG-8 normal
      mouse mammary epithelial and T47D human breast cancer cells, respond to Prl by
      rapid and transient activation of a series of kinases. Raf-1 was activated within
      2-5 min of Prl treatment. This was followed rapidly by activation of MEK (MAP
      kinase kinase) and MAP kinase activity in these cells. Increased MAP kinase
      activity was accompanied by tyrosine phosphorylation of both the 42 kDa and 44
      kDa isoforms. The tyrosine kinase inhibitors genestein and tyrphostin blocked the
      increase in MAP kinase activity as well as Prl induced growth of the T47D cells.
      These results indicate that the Prl receptor, after binding to Prl in mammary
      cells, activates the raf-MEK-MAP kinase pathway for signal transduction leading
      to mitogenesis.

PMID- 8879681
TI  - A prothrombotic state in breast cancer patients treated with adjuvant
      chemotherapy.
AB  - Cancer is often associated with abnormal activation of coagulation leading to a
      prothrombotic state. Some chemotherapeutic agents used for cancer may induce
      thrombosis but their biological alterations in the hemostatic system are not yet
      well understood. This study evaluated alterations of coagulative and fibrinolytic
      parameters following chemotherapy. In plasma samples of 38 patients (median age:
      49 years) receiving CMF (schedule 1-21 or 1-8) for Stage II breast cancer, we
      evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS),
      thrombin-antithrombin complex (TAT), prothrombin fragment F 1 + 2 (F 1 + 2),
      fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator
      inhibitor (PAI-1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with
      routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and
      PS were also evaluated with immunoenzymatic methods, t-PA, PAI-1, D-D, TAT, and F
      1 + 2 were measured with immunoenzymatic methods. All tests were performed
      immediately before starting therapy and after each cycle. A PC antigen decrease
      appeared soon after beginning therapy and lasted throughout chemotherapy. The
      lowest values were present after the first treatment both in the CMF 1-21 group
      (mean +/- SD = 72.5 +/- 10.8%) and in the CMF 1-8 group (mean +/- SD = 77.2 +/-
      6.9%): PC activity was also decreased. PS antigen decreased after the first
      administration (mean +/- SD = 73.3 +/- 10% in CMF 1-21 group, and 72.5 +/- 4.9%
      in CMF 1-8 group): PS activity also decreased. PAI-1 antigen levels increased
      (mean +/- SD = 43.1 +/- 20.4 ng/ml in the CMF 1-21 group, and 37.5 +/- 12.2 ng/ml
      in CMF 1-8 group) lasting up to the last cycle. CMF provokes a trend toward
      hypercoagulability; this effect should be considered when chemotherapy is
      employed in advanced cancer patients at high risk for thrombosis, or in patients
      with other risk factors.

PMID- 8879682
TI  - Does induction chemotherapy with a mitoxantrone/vinorelbine regimen allow a
      breast-conservative treatment in patients with operable locoregional breast
      cancer? A French Northern Oncology Group trial in 105 patients. French Northern
      Oncology Group.
AB  - BACKGROUND: In recent years, induction chemotherapy has been tested by several
      investigators in the management of operable breast cancer. PATIENTS AND METHODS:
      Our current study was aimed to evaluate, pragmatically, in patients (74 stage II
      and 30 stage III) whose treatment would have been mastectomy, the percentage of
      them in whom a conservative treatment can be performed if primarily treated with
      a mitoxantrone/vinorelbine regimen. RESULTS: 67/104 patients (64%; 95% CI: 55
      74%) had a conservative treatment (lumpectomy: 54, radiation therapy: 12,
      radiation therapy then lumpectomy: 1) Neutropenia was the major dose-limiting
      side effect, with grade 3 or 4 neutropenia registered in 83% of patients and
      53.3% of the 442 cycles. Overall, a grade 3 or 4 non hematologic side effect
      occurred in 19.8% of patients and in 9.1% of cycles. One toxic death was observed
      after 2 cycles in a patient with aplasia who developped septicemia. Seventy one
      per cent of the patients experienced nausea and vomiting but grade 3 were
      observed in only 12% of the patients. Other side effects, including stomatitis,
      asthenia, alopecia, and constipation, were generally mild and uncommon.
      CONCLUSIONS: This mitoxantrone/vinorelbine regimen is an efficient induction
      treatment with only neutropenia as a noticeable side effect. It allows 64% of
      conservative treatment in patients whose treatment would have been mastectomy.

PMID- 8879683
TI  - Prostate specific antigen in breast cancer, benign breast disease and normal
      breast tissue.
AB  - Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis
      and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that
      PSA may also be produced by breast tumors. In this report we examined
      quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast
      disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant
      amounts of PSA (> or = 0.030 ng of PSA per mg of total protein) were found in 28%
      of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA
      positivity in breast tumors was highest in stage I disease (34%) and decreased
      with disease stage (24% in stage II and 18% in stage III-IV). Using polymerase
      chain reaction amplification we have shown PSA mRNA presence in patients with PSA
      protein-positive tissues (benign and malignant) but not in patients with PSA
      protein-negative tissues. Our data suggest that PSA is expressed frequently by
      normal breast tissue, by tissue of benign breast diseases, and by breast cancer
      tissue. Highest expression is seen in benign breast disease and lowest expression
      in advanced stage cancerous tissue. As PSA production is mediated by steroid
      hormones and their receptors, we propose that PSA may be a new marker of steroid
      hormone action in the normal or diseased female breast. The role of this enzyme
      in the development of breast diseases including breast cancer is currently
      unknown.

PMID- 8879684
TI  - Intraoperative assessment of axillary lymph node metastases in operable breast
      cancer.
AB  - The diagnostic value of intraoperative histologic examination of frozen sections
      of axillary lymph nodes was investigated in 243 patients with operable breast
      cancer. One to six hard or enlarged axillary nodes were sampled from the axillary
      pad which was derived from a partial axillary dissection (including level 1 and 2
      nodes). Half of these nodes were histologically examined using frozen sections
      during surgery. After a total axillary dissection, both the axillary nodes in the
      partial axillary dissection and the nodes dissected at level 3 were
      histologically examined on permanent section. A mean of four nodes were sampled
      (range: 1 to 6). Axillary dissection yielded a mean of 22 nodes (range: 6 to 60).
      Axillary sampling detected the presence of metastases in 65 of 84 (77%) patients
      with positive axillary lymph nodes. In the patients in whom the axillary
      involvement was not identified by axillary sampling, however, the extent of
      axillary involvement was limited to levels 1 and 2. Therefore, a partial axillary
      dissection may be justified for patients in whom axillary involvement is not
      found on frozen section of nodes from axillary sampling, whereas a total axillary
      dissection should be performed for patients in whom axillary involvement is found
      by these procedures.

PMID- 8879685
TI  - Proliferation of the breast epithelium in relation to menstrual cycle phase,
      hormonal use, and reproductive factors.
AB  - The proliferative rate in normal breast epithelium from 58 women undergoing
      reduction mammoplastics was studied using the formalin resistant antibody Ki-S5,
      and related to age at operation, menstrual cycle phase, family history of breast
      cancer, height and weight, parity, and hormonal use. The breast tissue from women
      operated on in the luteal menstrual cycle phase (day 15-28 among oral
      contraceptive (OC) users) had significantly higher proliferative rate than breast
      tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among
      women presently exposed to hormones, those with a positive family history of
      breast cancer among first and second degree relatives had significantly higher
      values than cases without such history (p = 0.02). Weight was not significantly
      related to proliferation rate, while a short height was associated with a
      significantly higher proliferation rate (p = 0.04). Women who used OCs before the
      first full-term pregnancy (FFTP) had a significantly higher proliferation rate
      compared with never users or late users (p = 0.04). No significant difference was
      seen between parous versus nulliparous women. The results from the univariate
      analysis persisted in multivariate models. An especially high proliferation rate
      was seen in young women with both a positive family history and present hormonal
      use (p = 0.001). Overall, it was found that young women had a non-significantly
      higher proliferation rate than older women (p = 0.10). Due to small sample size,
      these results must be regarded as preliminary, especially in the subgroup
      analyses.

PMID- 8879686
TI  - Vascularity demonstrated by Doppler ultrasound and immunohistochemistry in
      invasive ductal carcinoma of the breast.
AB  - BACKGROUND: Vascularity is an important determinant of a tumour's ability to grow
      and disseminate. Breast tumour vascularity can be determined with doppler
      ultrasound (US) and by counting the vessels microscopically (microvascular
      density-MVD). The biologic characteristics of tumours based on their vascularity
      have not been extensively studied. METHOD: Preoperative US was performed on 207
      patients with invasive ductal breast carcinomas (IDC). MVD was assessed
      immunohistochemically using polyclonal antisera against factor VIII and the
      proliferation rate was measured with Ki-67 polyclonal antisera. Histologic tumour
      characteristics and oestrogen receptor (ER) status were determined. Thermography
      was performed on 174 of the patients. RESULTS: Twenty-five percent of IDC
      demonstrated US-vascularity. US-vascular tumours were more likely to be node
      positive, and had a higher mitotic rate than avascular cancers. US-vascularity
      was more common in tumours with MVD greater than 80 vessels/250x field than those
      with fewer vessels. The proliferation rate, histologic grade III, and nuclear
      grade III were higher and ER positivity lower, but the differences were not
      statistically significant. US-vascular cancers were associated with significantly
      more thermographic abnormalities. The cancer recurrence rate at three years was
      higher in patients with vascular cancers although the difference was not
      statistically significant. CONCLUSION: US appears to be a simple, non-invasive
      method of identifying vascular cancers associated with factors indicating a poor
      prognosis.

PMID- 8879687
TI  - Simultaneous expression of nitric oxide synthase and estrogen receptor in human
      breast cancer cell lines.
AB  - For various human tumor cell lines (neuroblastoma, cervix carcinoma) the presence
      of constitutive nitric oxide synthase (cNOS) has been documented. Here, for the
      first time, we report about cNOS expression in 10 of 16 human breast cancer cell
      lines. cNOS expression correlates strongly with expression of estrogen receptor
      (ER). Competitive reverse transcription-polymerase chain reaction (cRT-PCR) was
      used to detect cNOS and ER mRNA expression. Our findings suggest that estradiol
      could stimulate constitutive NO release in breast tissue, where it acts as a free
      radical.

PMID- 8879689
TI  - Coding of acoustic features for a single-channel tactile aid.
AB  - Measurements have been made on the discrimination of speech contrasts on the
      basis of single-channel vibrotactile presentation of a variety of speech-derived
      signals, coded as amplitude- and frequency-modulated pulse trains. Stimulation
      was at the index fingertip. The signals chosen for tactile presentation were the
      speech amplitude envelope, the voice fundamental frequency FO and the zero
      crossing frequency in the 1.3-6.6 kHz band. "Two-feature' codings, which present
      two of these signals simultaneously (one coded as stimulus frequency and one
      coded as stimulus amplitude), were found to be no more effective than "single
      feature' codings which present only one signal (coded as both amplitude and
      frequency). Scores for consonant discrimination were highest for the single
      feature coding of zero-crossing frequency, although differences between the
      codings were not, in general, significant. Scores for emphatic-stress
      discrimination were highest for the single-feature coding of F0, and this coding
      produced best results overall. A practical wrist-worn device, whose design is
      influenced by these experimental results is briefly described.

PMID- 8879688
TI  - A pilot investigation of high-frequency audiometry in obscure auditory
      dysfunction (OAD) patients.
AB  - The diagnosis of obscure auditory dysfunction (OAD) has been an elusive one,
      based primarily upon reports of poor speech perception in noise by the patient.
      Basic audiometric testing reveals hearing within normal threshold limits and it
      is thought that there may, in part be some subtle psychoacoustic and/or central
      auditory deficits causing this phenomenon. The use of high-frequency audiometry
      (HFA) as a test of subclinical cochlear damage has been well documented,
      especially to monitor the early effects of noise exposure and ototoxic drugs.
      However, it has not been used in the diagnosis of OAD patients. This study
      examines the use of HFA as an aid to the understanding of OAD pathophysiology.
      HFA was conducted on nine OAD subjects, each matched to two controls. Results
      indicate an elevated threshold amongst all frequencies (10-20 kHz) in OAD
      patients with significant differences occurring at 10, 14, 16 and 20 kHz. It
      could be postulated that OAD in fact, is the product of an ultra-high-frequency
      hearing impairment and its psychoacoustic sequelae. Furthermore, HFA may be a
      useful inclusion in a diagnostic test battery for OAD status. However, the degree
      to which it can be used may be limited due to the large intersubject variability
      in HFA thresholds in the normal population. It is suggested that further
      investigations into the ultra-high-frequency hearing abilities of OAD patients
      should be completed in the future.

PMID- 8879690
TI  - Simulation of multi-microphone hearing aids in multiple interference
      environments.
AB  - In this study, the advantages of Digital Signal Processing (DSP) hardware for
      hearing aids are investigated in the context of multiple microphone arrays. One
      key question in multiple microphone DSP system design remains the allocation of
      processing resources between the number of microphones and the number of
      adjustable tap weights applied to each microphone. This study addresses the
      appropriate distribution of these resources for currently implementable adaptive
      DSP systems. Comparisons are made by computer simulation that includes acoustic
      headshadow, reverberation effects and non-ideal microphone array hardware in a
      wide variety of environments. Variations in the number of interfering sources,
      the amount of reverberation and the microphone array configuration leads to
      several important conclusions. Performance improvements provided by the
      processors are reported as the broadband unweighted signal-to-babble ratio of pre
      emphasized speech and speech-shaped babble. Results are demonstrated for both
      fixed and robust adaptive systems.

PMID- 8879691
TI  - Feasibility of acoustic distortion product testing in newborns.
AB  - Acoustic distortion products (ADP) have been used as a neonatal screen for
      newborn, full-term infants resident on maternity wards. ADPs were measured across
      frequency with f2 (the higher frequency tone) between 1 and 8 kHz and the f1 (the
      low frequency tone) determined by f2/1.225. Testing was attempted on 77 infants.
      Of these, 13% were untestable, 69% were tested in both ears and 18% had one ear
      tested; 48% gave data from both ears and 25% gave data from one ear. If results
      from both ears were required to pass the test, 52% would fail. Of the 67 babies
      that could be tested, 27 out of 120 ears gave no result: a failure rate of 22.5%.
      It was often not possible to record ADP across all the frequencies tested, but
      only four babies out of the 31 who were tested at each frequency bilaterally
      showed no ADP at any frequency. Older babies (4-6 days old) gave distortion at
      more frequencies than younger babies (0-3 days old). ADP were most easily
      recorded with f2 at 3 and 4 kHz. Lower incidence of ADP at frequencies below 3
      kHz could be explained by greater levels of background noise. Left or right ears
      and method of delivery did not affect the ability to record ADP, but,
      unexpectedly, boys showed a higher incidence of ADP (though not higher level)
      than girls. Behavioural testing of the infants was carried out at 7 months of age
      without knowledge of the previous ADP test results. It yielded three referrals
      (out of 52 who could be followed up), one of whom was re-tested and passed. The
      two remaining infants were among the four who gave no distortion bilaterally,
      indicating accurate prediction by the ADP measure. It was concluded that ADP
      measurement alone at birth would lead to an unnecessarily large number of
      referrals for further investigation. This high failure rate may be reduced by
      measurement methods designed to avoid or cancel infant-generated noise, and by
      sound-treated facilities, but the lack of co-operation by the infant coupled with
      limited test time poses a more serious problem.

PMID- 8879692
TI  - The relationship between uncomfortable loudness level and maximum power output in
      subjects recently fitted with NHS hearing aids.
AB  - It is generally agreed that the maximum output from a hearing aid should not
      exceed the subject's uncomfortable loudness level (ULL). However, this
      relationship is not easily defined as electroacoustic data are usually measured
      in a 2 cc coupler and auditory measurements are usually obtained from supra-aural
      transducers calibrated in a 6 cc coupler. The aim of the study was to investigate
      this relationship in 21 adults who were being fitted with a hearing aid for the
      first time. A probe-tube microphone system was used to measure the sound pressure
      level of both variables in the ear canal. The measurement of ULL was determined
      using the method recommended by the British Society of Audiology (1987). The ULL
      values were around 110 dB SPL (+/-10) when measured in the ear canal. The maximum
      output of the hearing aid was obtained by correcting the SSPL90 with the
      subject's own real ear to coupler difference. The results revealed that the real
      ear saturation response (RESR) of the newly fitted hearing aid was typically 115
      120 dB SPL (+/-8). The RESR exceeded the ULL for 19 (90%) subjects on average at
      five of the seven frequencies and by 12 dB. While further research is needed to
      determine whether discomfort occurred in real life situations, the implications
      are that the subject may use the hearing aid at less than optimum settings to
      prevent loudness discomfort or may ultimately reject the hearing aid altogether.

PMID- 8879693
TI  - Evaluation of the E2L toy test as a screening procedure in clinical practice.
AB  - Early identification of hearing loss in young children is essential in order to
      avoid the potentially disabling effects of deafness. This necessitates effective
      screening measures with proven positive predictive value (McCormick 1977, 1988;
      Mahon et al., 1993). Previous studies (Marcuson et al., 1988; Bellman and
      Marcuson, 1991) have indicated that the E2L Toy Test, designed as a word
      discrimination test for evaluating the hearing of children who have English as a
      second language (E2L), could be such a measure. The results of diagnostic
      audiological testing, including the E2L test, are reported in 264 children.
      Comparison of E2L results with audiometric testing shows the E2L test to have a
      sensitivity of 87% and specificity of 90% in identifying children with an average
      hearing threshold of greater than 25 dB HL (and 78% sensitivity: 94% specificity
      where the average hearing threshold level is above 20 dB HL). This is the case
      for both E2L children and for children whose first language is English,
      suggesting that the E2L Toy Test would be useful in hearing screening test
      batteries throughout the UK. The results of screening hearing using the E2L Toy
      Test in 500 children aged 2-7 years from a wide geographical area in the UK are
      also presented.

PMID- 8879695
TI  - Tuberculosis: a growing problem.

PMID- 8879694
TI  - High dependency units: role and need.

PMID- 8879696
TI  - Radiology of pulmonary tuberculosis.
AB  - Pulmonary tuberculosis (TB) is a considerable health problem throughout the
      world, and has increased in incidence over the past 10 years. This article
      reviews the typical radiographical findings in post-primary TB and reactivation,
      and describes the less common manifestations of the disease in nonimmuno
      compromised and immuno-compromised individuals. Indications for plain
      radiography, computed tomography and high-resolution computed tomography are also
      discussed.

PMID- 8879697
TI  - Tuberculosis in the HIV-positive patient.
AB  - HIV infection is the most potent risk factor known for tuberculosis, which
      results both from reactivation and progression from recent infection. We review
      the epidemiology, clinical features, differential diagnosis and management of HIV
      associated tuberculosis, probably the most important opportunistic infection
      associated with HIV worldwide, and one that is communicable to other HIV-negative
      persons.

PMID- 8879698
TI  - Molecular diagnosis, detection of drug resistance and epidemiology of
      tuberculosis.
AB  - Tuberculosis remains one of the most common and important infectious diseases
      worldwide. Early diagnosis and detection of Mycobacterium tuberculosis drug
      resistance is vital for good clinical management and improving public health
      generally.

PMID- 8879699
TI  - Tuberculosis and immigration.
AB  - Immigration has altered the epidemiology and clinical pattern of tuberculosis in
      the UK. Clinical awareness needs to be high because of a 25-fold increased
      incidence in immigrant subgroups. Drug resistance is also increased. New
      immigrants should be screened for tuberculosis.

PMID- 8879700
TI  - Management of invasive bladder cancer.

PMID- 8879701
TI  - Modern management for testicular teratoma.

PMID- 8879702
TI  - The management of poor prognosis teratoma.

PMID- 8879703
TI  - First trimester pregnancy: ultrasound and biochemical evaluation.

PMID- 8879704
TI  - Bioavailability of two clodronate formulations.
AB  - Sodium clodronate is effective in the management of osteolytic lesions,
      hypercalcaemia and bone pain associated with skeletal metastasis. Clinical and
      biochemical data underpin a licensed total daily dose of 1600-3200 mg.

PMID- 8879705
TI  - Elder abuse.
AB  - Abuse of old people is an uncomfortable concept for health professionals. The
      phenomenon raises important questions about how we care for the older members of
      society and demands scrutiny of many moral precepts, such as respect for
      autonomy, beneficence and non-maleficence. In common with the mistreatment of any
      group of individuals, elder abuse is not new, but until recently it has not been
      widely recognized, reflecting professional unfamiliarity with this difficult and
      challenging problem.

PMID- 8879706
TI  - Hepatitis G virus: identification and prevalence.
AB  - A new flavivirus, provisionally designated as hepatitis G virus, has recently
      been identified. Its genomic organization is similar to that of the hepatitis C
      virus (HCV) with which it has only 25% nucleotide homology. The virus is
      transmissible by blood transfusion, by exposure to blood products or by
      intravenous drug use. Concurrent infection with hepatitis B virus and HCV is
      common and persistent viraemia has been documented, in many cases in the absence
      of transaminase elevations.

PMID- 8879707
TI  - Whose life is it anyway?

PMID- 8879708
TI  - Postgraduate medical education and flexible training.
AB  - The importance of opportunities to train and work on a flexible basis are
      emphasized, particularly in the light of current medical staffing shortages in
      the NHS and the need to use resources effectively. The profile of the medical
      workforce is very different now compared with 40 years ago, and career pathways
      must therefore be modified.

PMID- 8879709
TI  - Community psychiatry: central policy, local implementation.

PMID- 8879710
TI  - An ethological approach to self-injury.

PMID- 8879711
TI  - Factitious illness by proxy. Munchausen syndrome by proxy.
AB  - BACKGROUND: Since 1977 a literature has grown describing examples of factitious
      illness by proxy (FIP). METHOD: The literature in English was searched using
      MEDLINE and supplemented by a manual search. Extracted data focused on
      terminology of a spectrum of behaviours, clinical features and psychopathology of
      perpetrators. RESULTS: There has been difficulty with the use of terminology and
      classification of psychiatric disorders. CONCLUSIONS: The spectrum of FIP is
      wide. Suggestions are made for the use of terminology and classification when FIP
      is identified.

PMID- 8879712
TI  - The benzodiazepine dependence questionnaire: development, reliability and
      validity.
AB  - BACKGROUND: A short self-report questionnaire was developed to assess dependence
      on benzodiazepines (BZDs), the Benzodiazepine Dependence Questionnaire (BDEPQ).
      The BDEPQ is the first scale to assess dependence on BZDs comprehensively, as all
      existing scales focus exclusively on withdrawal symptoms. METHOD: To evaluate its
      internal consistency and construct validity, 302 regular BZD users were recruited
      from media advertisements and assessed on a number of measures. The BDEPQ was
      compared with measures of depression, anxiety, sleep quality, BZD withdrawal
      symptoms and neuroticism to assess its construct validity. A 3-4 month follow-up
      was conducted to assess the ability of the BDEPQ to predict changes in BZD
      consumption and future BZD withdrawal. RESULTS: The BDEPQ was found to have high
      internal consistency and to be relatively stable over the follow-up period. Three
      subscales were identified, each with good internal consistency and temporal
      stability. The BDEPQ was able to predict the severity of withdrawal symptoms.
      CONCLUSION: The BDEPQ was found to be a reliable and valid self-report instrument
      for the assessment of BZD dependence in samples approximating the general
      population of people using BZDs.

PMID- 8879713
TI  - Ten-year prognosis of conversion disorder.
AB  - BACKGROUND: Previous work suggests neurological disease commonly supervenes in
      cases of conversion disorder but has not identified clear predisposing factors.
      Patients' subsequent use of services has been neglected. METHOD: Clinical
      outcomes for 73 patients investigated for pseudoneurological symptoms at a
      neurological hospital 10 years earlier were compared with findings on
      presentation. Fifty-six patients complied with a structured interview concerning
      use of services. RESULTS: Thirty patients had no relief from their original
      symptom at follow-up. They had been older, with more chronic symptoms, and
      different auxiliary psychiatric diagnoses. In 11 patients a clear neurological
      diagnosis was subsequently made for the original symptom. Provisional
      neurological diagnoses at presentation had been disproportionately common among
      these 11. Small numbers of patients with poor outcomes made most use of hospital
      and community services. High attenders met screening criteria for somatisation
      disorder at follow-up. CONCLUSIONS: The prognosis for chronic symptoms remains
      poor, but subsequent rediagnosis of neurological disease is less frequent than
      commonly supposed. Somatisation disorder may develop if hospital contact does not
      lead to diagnosis of another disease.

PMID- 8879714
TI  - The TAPS project. 36: the most difficult to place long-stay psychiatric in
      patients. Outcome one year after relocation. Team for the Assessment of
      Psychiatric Services.
AB  - BACKGROUND: The clinical and social outcomes were evaluated of "difficult to
      place" (DTP) patients discharged from hospital to alternative facilities. METHOD:
      In the course of a reprovision programme for a psychiatric hospital, 72 long-stay
      patients were considered to be too problematic to live within the usual range of
      community placements. Their clinical and social state was assessed shortly before
      the hospital closed. Severe, persistent behavioural problems were recorded for
      each subject at baseline. One year after being relocated, patients were
      reassessed. RESULTS: Clinical and social measures were stable over time. The
      profile of severe behavioural problems changed over time, with one-third of the
      total problems subsiding and a similar number of new problems emerging. There was
      a significant reduction in physical aggression. One of the settings provided an
      environment as free of restrictions as the usual community homes. CONCLUSIONS:
      The most difficult patients to reprovide for can be contained in a relatively non
      restrictive care environment. There is some indication that aggressive behaviour
      can improve, raising the possibility that some DTP patients can move on to the
      usual community homes.

PMID- 8879715
TI  - Manchester and Oxford Universities Scale for the Psychopathological Assessment of
      Dementia (MOUSEPAD).
AB  - BACKGROUND: There is increasing awareness of the importance of psychopathological
      and behavioural changes in dementia and a need for an instrument to measure these
      features which achieves an appropriate compromise between brevity and breadth. We
      describe a newly developed 59-item instrument: the MOUSEPAD. METHOD: Reliability,
      sensitivity and validity were examined with 30 carers, each of whom was
      interviewed four times over six weeks. RESULTS: For different symptom groups,
      kappa ranged from 0.43 to 0.93 for test-retest reliability, from 0.56 to 1.0 for
      inter-rater reliability, and from 0.43 to 0.67 for the validation study.
      CONCLUSIONS: The scale may be useful as an outcome measure in drug trials, for
      correlating psychopathological and behavioural changes with post-mortem findings,
      and in epidemiological surveys.

PMID- 8879716
TI  - An index of need for psychiatric services based on in-patient utilisation.
AB  - BACKGROUND: The paper describes the development of an index of the relative need
      for psychiatric services for the purposes of distributing NHS funds in England.
      METHOD: The study is based on an empirical analysis of all psychiatric in-patient
      completed episodes in England in 1991/92. Any index of need should be independent
      of the effect of variations in health care supply on the use of psychiatric
      services. In order to disentangle the influences of supply from social and
      clinical determinants of utilisation, two stage least squares regression and
      multilevel modelling techniques were used. RESULTS: The outcome was an index
      comprising six health and socio-economic variables. This is now being used by the
      NHS Executive to distribute about pound 2.2 billion of annual NHS expenditure for
      psychiatric services between English health authorities. CONCLUSION: It is shown
      that the index is much more sensitive to needs and therefore more redistributive
      than the previous index of need used in the NHS.

PMID- 8879719
TI  - Impulsivity in disordered eating, affective disorder and substance use disorder.
AB  - BACKGROUND: Failure to control impulsive behaviour has been postulated as an
      underlying mechanism common to substance use disorder, sociopathy and to a
      substantial subgroup of women with bulimia nervosa. METHOD: Three hundred and one
      women recruited to a general population study were selected either at random or
      because they had lifetime substance use disorder, affective disorder or symptoms
      of bulimia. A subsequent interview determined the existence of problems with
      impulsivity. Behaviour that is an integral part of a DSM-III axis 1 disorder was
      excluded from the impulsivity measure. RESULTS: Similar rates of impulsivity were
      found in all three of these types of disorder, and this was little different from
      the rate found in the women selected randomly from the general population.
      However, among those with comorbid disorder there was more impulsivity, and the
      more comorbid disorders found, the higher the proportion with problems of
      impulsivity. CONCLUSIONS: Because those in treatment facilities are more likely
      to have other comorbid disorders (Berkson's bias), findings derived from
      observations of women with bulimia who are in treatment may be compromised by
      selection bias and may have limited applicability to those with the disorder who
      are not in treatment.

PMID- 8879718
TI  - Who responds to electroconvulsive therapy? A comparison of effective and
      ineffective forms of treatment.
AB  - BACKGROUND: It has been reported that real ECT is more effective than simulated
      treatment among depressed patients with delusions and/or retardation, and that
      ECT is not effective among depressed patients who lack these features. METHOD: In
      two randomised, double-blind studies, 143 patients with major depression were
      subtyped regarding psychosis, retardation and agitation. In both studies, low
      dosage, right unilateral ECT was ineffective compared with other forms of ECT.
      This report examined whether the depressive subtypes differed in clinical
      response to the ineffective and effective forms of ECT. RESULTS: The therapeutic
      advantage of effective forms of ECT was similar across the depression subtypes.
      Patients who lacked both psychosis and retardation showed this pattern.
      CONCLUSIONS: The findings cast doubt on the utility of these depression subtypes
      in predicting ECT response. ECT is a viable treatment option for patients with
      major depression regardless of the presence or absence of psychosis, retardation
      and/or agitation.

PMID- 8879720
TI  - Mental health, "burnout' and job satisfaction among hospital and community-based
      mental health staff.
AB  - BACKGROUND: Concerns have been expressed that staff burnout may make community
      mental health care difficult to sustain. This study compares stress and job
      satisfaction between community and hospital-based staff. METHOD: The GHQ-12, the
      Maslach Burnout Inventory and a job satisfaction measure were used to study 160
      Inner London staff. RESULTS: Community staff scored significantly higher on the
      GHQ-12 and the "emotional exhaustion' component of the Maslach Burnout Inventory
      than hospital-based in-patient, day care or out-patient staff. Satisfaction did
      not vary significantly between settings. CONCLUSIONS: These results may be
      explained in several ways. Community work may be inherently more stressful than
      hospital work, or may currently be stressful because of inadequate resources,
      training or supervision. The results may also reflect widespread recent changes
      in community services or the specific effects of working in a deprived area.

PMID- 8879721
TI  - Fragile states of mind: neuroticism, vulnerability and the long-term outcome of
      depression.
AB  - BACKGROUND: This paper considers the extent to which vulnerability to the outcome
      of major affective disorder is conferred through personality deviance. Results
      are based upon a 12 year longitudinal follow-up study of 80 patients with a
      primary depressive disorder, originally selected from a consecutive series
      seeking care at a hospital in Scotland. METHODS: The study included detailed
      clinical course assessments in association with the formal application of
      diagnostic criteria. Assessments on recovery from the index episode included
      measures of self-confidence and of neuroticism. Experience of selected severe
      loss events over the study period was also determined. RESULTS: Limited self
      confidence was strongly related, unlike neuroticism, to the subsequent first
      recurrence of affective disorder. Relationships between psychosocial, clinical
      and demographic factors and long-term outcome revealed psychosocial factors, in
      particular neuroticism and a lack of self-confidence, to have the greatest
      prognostic significance. CONCLUSIONS: These results reveal the heightened risk
      over the long-term of a poor outcome for depressive disorder consequent upon
      measures of personality deviance and of exposure to adversity. While giving only
      limited support to narrowly defined psychosocial models of depression, they
      clarify the risk gradients involved and through this may provide a firmer basis
      than hitherto for relapse prevention.

PMID- 8879723
TI  - Sexual abuse in people with alcohol problems. A study of the prevalence of sexual
      abuse and its relationship to drinking behaviour.
AB  - BACKGROUND: There is evidence that people with a history of sexual abuse may have
      an increased risk of developing alcohol and drug problems. METHOD: A self
      completion sexual abuse questionnaire was designed and administered to a sample
      of attenders at three London alcohol services. Drinking behaviour was assessed
      using the Severity of Alcohol Dependence Questionnaire and the Alcohol Problems
      Questionnaire, and additional data were derived from case notes. RESULTS: Fifty
      four per cent of women and 24% of men identified themselves as victims of sexual
      abuse or assault For the majority this had started before the age of 16 and
      involved non-relatives. Subjects with a history of sexual abuse were younger,
      reached drinking milestones earlier, were more likely to have a family history of
      alcohol misuse and had more alcohol-related problems than non-abused subjects.
      Sexual abuse, age and alcohol dependence predicted level of problems in a
      regression analysis. CONCLUSIONS: The high rates of sexual abuse and its
      association with indications of increased morbidity suggest it is an important
      issue for the management of alcohol problems. More use could be made of self
      completion questionnaires for the investigation of sexual abuse.

PMID- 8879722
TI  - Single photon emission computerised tomography in chronic alcoholism. Antisocial
      personality disorder may be associated with decreased frontal perfusion.
AB  - BACKGROUND: We examined the functional and structural cerebral changes in chronic
      alcoholics, analysing their association with personality features and alcohol
      drinking habits. METHOD: Forty patients with alcohol dependency, including 15
      with antisocial personality disorder (ASP) as defined in DSM-III-R and 10 age and
      sex matched healthy controls were studied after termination of withdrawal
      symptoms, using high resolution single photon emission tomography (SPECT),
      cranial computerised tomography (CT) and brainstem auditory evoked potentials
      (BAEP). RESULTS: We found significant reductions in regional cerebral blood flow
      (rCBF) measurements of alcoholic patients. Low flow in frontal regions
      encountered in 67.5% of the patients was associated with the duration of alcohol
      consumption, while no such relation existed with the amount of daily intake.
      Patients with ASP exhibited more marked frontal hypoperfusion. Significant brain
      atrophy detected by CT was present in 40% of the patients and did not correlate
      with frontal hypoperfusion. CONCLUSIONS: Patients with ASP are more sensitive to
      toxic effects of alcohol. Alternatively chronic alcoholism leads to frontal lobe
      dysfunction recognised as ASP in the clinical setting.

PMID- 8879724
TI  - Long-term stability of diagnosis and symptom dimensions in a systematic sample of
      patients with onset of schizophrenia in childhood and early adolescence. I:
      nosology, sex and age of onset.
AB  - BACKGROUND: Little is known about the long-term outcome of schizophrenia that has
      its onset during childhood and early adolescence (early-onset schizophrenia, or
      EO-SZ). Whether or not EO-SZ is an aetiologically separate form of schizophrenia
      (SZ) is unresolved. METHOD: The study was a 14.8-year follow-up, using methods
      such as systematic sampling, evaluation of possible non-respondent bias,
      consensus best-estimate diagnoses (DSM-III-R) made independently in childhood and
      adulthood, measures of positive and negative dimensions, of non-psychotic
      behaviour disturbances (NPBD) and of developmental problems before the appearance
      of SZ. RESULTS: There was high stability of EO-SZ (n = 40) diagnoses (mean onset
      at 14.0 years) until adulthood (mean age at follow-up 28.8 years) but a lower
      stability of positive and negative schizophrenic dimensions. There was a poor
      outcome of EO-SZ, a strong over-representation of males but few gender
      differences, and no effect of age of onset on clinical features and outcome.
      CONCLUSIONS: EO-SZ taken as a whole shows no qualitative differences to adult
      onset SZ. However, a distinction through the onset of preschizophrenic
      developmental problems or NPBD might be a way to investigate heterogeneity within
      EO-SZ.

PMID- 8879725
TI  - Creativity.

PMID- 8879726
TI  - Creativity.

PMID- 8879727
TI  - 'Audible thoughts' and 'speech defects' in schizophrenia.

PMID- 8879728
TI  - 'Audible thoughts' and 'speech defects' in schizophrenia.

PMID- 8879729
TI  - Clozapine-induced hypersalivation and the alpha-2 adrenoceptor.

PMID- 8879730
TI  - Influences on cost effectiveness.

PMID- 8879731
TI  - Cytochromes and psychotropic drug interactions.

PMID- 8879732
TI  - Consent to treatment.

PMID- 8879733
TI  - Consent to treatment.

PMID- 8879734
TI  - Obstetric complications and schizophrenia.

PMID- 8879735
TI  - Excess mortality of mental illness.

PMID- 8879736
TI  - More cases of paroxetine withdrawal syndrome.

PMID- 8879737
TI  - Yohimbine and sinusitis.

PMID- 8879738
TI  - Does the cervical canal to body ratio predict spinal stenosis?
AB  - The exact size of the bony cervical spinal canal and the vertebral body was
      measured in 368 cadaveric adult male vertebrae. A comparison of radiographic and
      direct measurements was also undertaken. The mean sagittal diameter of the spinal
      canal for C3-C7 was close to 14 mm (14.07 +/- 1.63 mm; N = 272). The mean ratio
      of the sagittal canal diameter to the vertebral body diameter (canal to body
      ratio) was 86.68 +/- 13.70 mm. Thirty-one percent of subaxial vertebrae would be
      diagnosed as having spinal stenosis if a canal to body ratio of less than 80% was
      considered abnormal. Measurements from plain radiographs overestimate the canal
      diameter. The average diameter for the lower cervical spinal canal is about 14
      mm. The canal to body ratio is independent of radiographic magnification, but may
      produce misleading results.

PMID- 8879739
TI  - Coracoacromial ligament function: a phylomorphic analysis.
AB  - Various morphologic parameters of the coracoacromial region were quantified for
      five hominoid genera to examine the evolutionary development of the
      coracoacromial ligament (CAL) and its significance and relationship to shoulder
      function. No evolutionary correlation within the family Hominoidea was found for
      several calculated parameters obtained from osseous dimensions and CAL length.
      However, from an evolutionary analysis of the order Anthropoidea, it appears that
      the CAL is not solely a vestigial structure in humans but rather represents a
      stage in the development of the hominoid shoulder with the function of providing
      increased mechanical stability to the superior bony vault.

PMID- 8879740
TI  - Ewing's sarcoma of the hand: a case report.
AB  - Ewing's sarcoma is a primary bone neoplasm that rarely occurs in the hand. Two
      cases are presented and comparison is made with Ewing's sarcoma of the long
      bones.

PMID- 8879741
TI  - Retrograde intramedullary nailing of the femur using a tibial nail--the
      adjunctive use of an existing implant: a case report.
AB  - A 74-year-old male involved in a pedestrian-automobile collision sustained a
      comminuted supracondylar-diaphyseal femur fracture. The fracture was stabilized
      by retrograde intramedullary fixation with a Synthes unreamed tibial nail. Knee
      motion reached 0 degree-120 degrees by the sixth postoperative day and the
      fracture healed within twelve weeks. Twelve months after his injury, his knee
      motion was symmetric to his uninjured side and he had resumed full preinjury
      activities, including martial arts training. Although antegrade intramedullary
      nailing remains the treatment of choice for fractures of the femur, this case
      highlights the usefulness of retrograde nailing and demonstrates the adjunctive
      application of an existing implant, the tibial nail, in certain special trauma
      situations.

PMID- 8879742
TI  - The use of customized long stem hemiarthroplasty in ipsilateral femoral neck and
      pending shaft fracture: case report.
AB  - Most orthopaedic units do not have long stem femoral hemiarthroplasty prosthesis
      in their inventory. Situations that require replacement of the femoral head and
      internal fixation of the ipsilateral femoral shaft include femoral neck and shaft
      fracture as a result of either trauma or metastasis. The author reports on one
      technique of solving this problem by the use of an Austin-Moore hemiarthroplasty
      in combination with a half sawed Gross-Kempf (GK) intramedullary nail. The length
      of the GK nail was tailored according to the measured femoral length. The two
      implants were then impacted with a 4 cm overlap. Additional security was provided
      by the tension band wire placed between one of the distal locking holes in the
      nail and the hole in the Austin-Moore' implant and tunneled through the
      intramedullary nail.

PMID- 8879743
TI  - Carcinomatous perforation of the sigmoid colon presenting as a thigh mass.
AB  - We report a patient presenting with a left psoas abscess causing necrotizing
      fasciitis of the upper thigh. The patient underwent exploration of the left thigh
      through a medial approach, confirming necrotizing fasciitis of the adductor
      compartment and the femoral triangle. The infective process also involved the
      left psoas. This was explored retroperitoneally through a left pararectal
      laparotomy incision. Further exploration revealed a carcinomatous ulcer of the
      sigmoid colon. Despite active resuscitation, antibiotic therapy, and further
      debridement, the patient died three days after admission.

PMID- 8879744
TI  - Salmonella braenderup sacroiliac osteomyelitis in a nonsickle cell patient: case
      report.

PMID- 8879745
TI  - Fracture-dislocation of the neck of the talus in a ten-year-old child: a case
      report and review of the literature.
AB  - A ten-year-old female underwent open reduction and internal fixation of a Hawkins
      type III fracture of the talar neck. The fracture united within three months.
      However, avascular necrosis of the body of the talus occurred. Partial collapse
      of the talar body ensued despite protection from weight-bearing for eight months
      after surgery. This case illustrates that fracture-dislocation of the talus can
      occur in a child and has a guarded prognosis.

PMID- 8879746
TI  - Brachial plexus injury in association with fracture-dislocation of the shoulder.
AB  - Anterior dislocation of the shoulder is generally not associated with
      neurological compromise. We report three patients in whom a brachial plexus
      injury was caused by an anterior dislocation of the shoulder. One patient was
      further complicated by vascular involvement. The forces producing the injury are
      usually small, and the neurological trauma is likely to be neuropraxia.
      Conservative management is usually successful, and, in our patients, recovery
      took place after an average of six months.

PMID- 8879747
TI  - A new operation for arthroplasty of the hip based on biomechanics,
      photoelasticity, fast-setting dental acrylic, and other considerations. 1953
      [classicle article].

PMID- 8879748
TI  - Tyrosine hydroxylase-negative, dopaminergic neurons are targets for transmitter
      depleting action of haloperidol in the snail brain.
AB  - 1. The effects of long term administration of micromolar concentrations of the D2
      antagonist haloperidol upon monoaminergic neurons in the snail Lymnaea stagnalis
      was investigated. 2. Treatment by bath application with 0.5-2.0 micromolar
      haloperidol, caused a significant, continuous depletion of dopamine levels in the
      nervous system as revealed by high performance liquid chromatography. 3. A
      transient depletion of serotonin was also observed, but DOPA and norepinephrine
      levels were unaffected. Similar depletion of dopamine was observed after the land
      snail, Achatina fulica, was injected with haloperidol on each of 4 consecutive
      days. 4. The depletion of dopamine as revealed with glyoxylate-induced
      fluorescence in Lymnaea appears to be restricted to a subpopulation of
      catecholaminergic neurons which are immuno-negative for tyrosine hydroxylase, the
      synthetic enzyme responsible for the conversion of tyrosine to DOPA. 5. The
      results thus demonstrate a depleting action of low micromolar doses of chronic
      haloperidol on specific subsets of dopaminergic neurons and a novel preparation
      for studying catecholaminergic mechanisms operating across the animal kingdom.

PMID- 8879749
TI  - Isolation and characterization of the highly phosphorylated repeat domain of
      distinct heavy neurofilament subunit (NF-H) isoforms.
AB  - 1. Recent examination of the hypothesis that distinctly phosphorylated NF-H
      isoforms exist in different types of neurons revealed that the extent of
      phosphorylation of the heavy neurofilament polypeptide of bovine ventral root
      motor neurons is markedly higher than that of dorsal root neurons. 2. In the
      present study we employed endoproteinase ASP-N for isolating the Lys-Ser-Pro
      (KSP)-rich domain of NF-H, which contains most of the NF-H phosphorylation sites.
      3. Treatment of NF-H with ASP-N endoproteinase results in a cascade of products,
      the last of which is a polypeptide with apparent molecular weight of 120 kDa.
      Amino terminal sequence and amino acid composition analysis revealed that this
      fragment contains the KSP-rich domain of NF-H. 4. Treatment of ventral and dorsal
      root NF-H with ASP-N endoproteinase and analysis of the phosphoserine contents of
      the resulting 120 kDa fragments revealed that the 120 kDa fragment of ventral
      root NF-H is significantly more phosphorylated than that of dorsal root NF-H. 5.
      These findings show that the difference in extent of phosphorylation of ventral
      and dorsal root NF-H is due at least partly to the KSP-rich domain of NF-H.

PMID- 8879750
TI  - Expression of platelet-derived growth factor (PDGF) receptor alpha-subunit in
      mouse brain: comparison of Patch mutants and normal littermates.
AB  - 1. Platelet-derived growth factor (PDGF) plays an important role not only in
      mesenchyme-derived tissues, but also in the mammalian central nervous system. The
      Patch mutant (Ph/+) lacks one copy of the PDGFR-alpha gene. However, it is not
      clear whether there are differences in expression of PDGF receptor alpha-subunit
      (PDGFR-alpha) in brain tissue of the Patch heterozygous (Ph/+) mutants compared
      to wild-type C57Bl (+/+) mice. 2. The level of PDGRF-alpha mRNA expression is
      slightly lower in Patch mutant than in normal littermate. 3. Protein and total
      RNA isolated from mouse brain tissue and primary type 1 astrocyte cultures were
      studied with Western and Northern blotting techniques. There was no measurable
      difference ir PDGFR-alpha protein expression between the Patch and wild-type
      mouse nervous system. Adjustment of transcriptional efficiency and messenger
      stability may contribute to this phenomenon, whose biological significance
      remains unclear. 4. Further, the expression of PDGRF-alpha protein and message in
      mouse brain tissues is developmentally regulated. Its level remains high during
      the embryonic period and declines below measurable levels in adult.

PMID- 8879751
TI  - Low concentrations of ouabain stimulate Na/Ca exchange in neurons.
AB  - 1. The effects of low concentrations of ouabain on 22Na efflux, 86Rb influx, 45Ca
      uptake and cyclic AMP levels were studied in snail ganglia. Ouabain, at
      concentrations below that which inhibits the Na-K pump as monitored by 86Rb
      influx, activated "reverse mode" Na/Ca exchange, as indicated by an increased
      22Na efflux and 45Ca influx. 2. With electrophysiologic recordings ouabain, in
      the presence of K(+)-free saline to block Na/K transport, caused a membrane
      hyperpolarization. These concentrations of ouabain also caused elevation of
      intracellular cyclic AMP levels. 3. We suggest that the ouabain-induced
      stimulation of Na efflux is due to a stimulation of reverse Na/Ca exchange. since
      Na/Ca exchange is electrogenic, these observations are most consistent with
      ouabain stimulation of Na/Ca exchange in a reversed direction (intracellular Na
      for extracellular Ca). 4. The effect on Na/Ca exchange may be secondary to a rise
      in intracellular cyclic AMP.

PMID- 8879752
TI  - Neuronal isoform of nitric oxide synthase is expressed at low levels in human
      retina.
AB  - 1. The expression of neuronal isoform of nitric oxide synthase (nNOS) was studied
      in human retinal tissues. The cDNA sequence was cloned in human retinal poly (A)+
      RNA by the RT-PCR method and encompassed an open-reading frame of 4,302 bp
      encoding 1,434 amino acids. This sequence showed a possibility of genetic
      polymorphism in comparison to human brain form. 2. Restriction fragment length
      polymorphism (RFLP) patterns of a partial cDNA fragment suggest that there is
      genetic polymorphism in the neuronal form of NOS. Important differences were
      observed in a certain region between human retinal and brain froms. This region
      is a result of frame shift by the addition of three cytidines. In this study,
      regions from human brain (cerebellum) and skeletal muscle as well as retina were
      sequenced to confirm the difference in this region. The sequences from these
      tissues were completely identical. This indicated that genetic polymorphism of
      nNOS gene was due to single base substitution and not frame shift phenomenon by
      addition or deletion of bases. 3. The nNOS mRNA of approximately 12 kb was
      detected by northern blot analysis. The lower level of the expression was
      distinguished in comparison to those of human brain and skeletal muscle. The cDNA
      transiently transfected into CHO-K1 cells expressed a protein which contained a
      significant level of NOS activity. The size of the nNOS was found to be
      approximately 160 kDa by both in vitro and in vivo translation systems. This NOS
      was calcium dependent and the K(m) for arginine was 4.4 microM. 4. The Ca+2, L
      arginine and NADPH dependency along with the inhibitory effect of N-nitro-L
      arginine on NOS activity were evaluated. The finding of a constitutive from of
      NOS in human retina, which is calcium-NADPH dependent, gives further credence to
      the possible role of nitric oxide in retinal function and neuronal diseases.

PMID- 8879754
TI  - The more the merrier? Effects of family size and sibling spacing on sibling
      relationships.

PMID- 8879753
TI  - Myelin-stimulated macrophages release neurotrophic factors for adult dorsal root
      ganglion neurons in culture.
AB  - 1. Our previous study demonstrated that cultured macrophages release neurotrophic
      factors spontaneously. In a histological study of Wallerian degeneration,
      macrophages phagocytosed myelin debris and expressed activated markers. 2. To
      investigate the role of myelin-stimulated macrophages on neurite regeneration, we
      prepared conditioned media from cultured mouse peritoneal macrophages which had
      phagocytosed a myelin fraction. This conditioned media enhanced both neurone
      survival and neurite regeneration of adult dorsal root ganglia (DRG) neurons
      compare to conditioned media from macrophage cultures without myelin. 3. The
      production of the neurotrophic supernatant was dose-dependent on myelin fraction
      and specific for myelin because supernatants from macrophages incubated with LPS
      (lipoplysaccharide), MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine) or latex beads
      were not neurotrophic. 4. The neurotrophic factors from myelin-stimulated
      macrophages were different from spontaneously released macrophage factors as they
      differed in heat-sensitivity. 5. These results suggest that myelin-stimulated
      macrophages contribute to axon regeneration after Wallerian degeneration.

PMID- 8879755
TI  - Letter writing to parents following paediatric outpatient consultation: a survey
      of parent and GP views.
AB  - This study examined the practice of writing to parents following paediatric
      outpatients consultation (general practitioners (GPs) receive a copy of the
      letter to parents). One hundred and three questionnaires were sent to both
      parents and GPs in order to elicit their views. Fifty-one parents responded (RR
      50.5%) and 56 GPs (RR 54.4%). All parents were in favour of the idea of
      specialists writing directly to parents/patients and none of the parents were in
      favour of the letter being sent to the GP alone. The majority of GPs considered
      that the letter(s) would improve parental satisfaction (85.7%) and improve
      compliance with medical advice (83.3%); 83.6% of GPs stated that the copy of the
      letter to parents was at least as helpful, if not more so, than the usual type of
      clinic letters they receive. Despite this, GPs expressed mixed feelings about the
      idea of all specialists writing direct to patients/parents, with 46.3% in favour
      of the idea and 40.7% against.

PMID- 8879756
TI  - Research into the lifeworld of physically disabled children.
AB  - This article presents a phenomenological study of the experiences of physically
      disabled children. The research focuses on elementary school aged children not
      suffering from additional intellectual disability. In previous research we
      noticed just how often the children we observed are considered and discussed from
      the point of view of professional expertise. There is, for instance, the medical
      account of the disorder, the paramedical view concerning the treatment of the
      physical limitations and the educational and psychological approach to learning
      disabilities. Our research aims to highlight the perspective of the disabled
      child him- or herself. We let the children speak for themselves on their three
      'favourite' subjects: on their bodies, on friends and on parents and experts.

PMID- 8879757
TI  - Masturbation in prepubescent children: a case report and review of the
      literature.
AB  - A 10-year-old girl observed to have episodes of flushing, pallor and weakness,
      was referred for investigation of possible carcinoid syndrome. The cause of these
      episodes was masturbation. Masturbation occurs at all ages and in most cases is
      considered normal behaviour. Lack of recognition of this phenomenon in children
      may lead to unnecessary investigations and treatment.

PMID- 8879758
TI  - Race and ethnicity as determinants of child health: a personal view.
AB  - 'Race' and ethnicity are widely studied as explanatory variables in health
      research and their apparent independent effects are reported to explain many
      health variations between different groups within and between populations. Both,
      however, are associated with major problems of definition and confusion of socio
      cultural and biological concepts which call into question the validity of many of
      the 'independent' effects attributed to them. This paper seeks to unravel the
      basis of these concepts and explore their scientific validity using examples from
      the child health literature.

PMID- 8879759
TI  - Some implications of the 1993 Education Act.

PMID- 8879760
TI  - Cyclospora: an overview.

PMID- 8879761
TI  - Prevention of perinatal transmission of human immunodeficiency virus: a progress
      report 2 years after completion of AIDS Clinical Trials Group trial 076.
AB  - In this AIDS commentary, Dr. Wilfert has reviewed the American experience with
      vertical transmission of human immunodeficiency virus type 1 (HIV-1) since the
      closing of the 076 trial performed by the AIDS Clinical Trials Group in February
      1994. The news generally is good; the rate of transmission from mother to child
      in nonstudy situations has been reduced when counseling and therapy are offered
      to pregnant women. As Dr. Wilfert emphasizes, the mechanism of the beneficial
      effect remains to be elucidated. More important, the resources required to insure
      that women have access to counseling and care need to be secured. In addition to
      these issues discussed by Dr. Wilfert, questions that need to be addressed
      include the efficacy and safety of more-potent antiretroviral agents or
      combinations in further reducing the risk of transmission, the optimal
      intervention for women who become pregnant while receiving antiretroviral
      therapy, the optimal postpartum management for women, and the most-effective
      treatment strategy for children born to infected women. The newborn child who is
      infected in spite of treatment of the mother potentially could receive great
      benefit from aggressive therapy designed to reduce the rate of viral replication
      and the selection of drug-resistant HIV-1. Finally, inexpensive and user-friendly
      methods of reducing the rate of vertical transmission in developing countries are
      urgently needed. Progress in reducing the prevalence of pediatric HIV-1 infection
      transmitted by mothers, the most common source of this infection in children, has
      been made, but further research and effort to insure access to care and answers
      to unsolved problems are necessary.

PMID- 8879762
TI  - Microbiology and laboratory diagnosis of upper respiratory tract infections.
AB  - In the article that follows, Carroll and Reimer address a number of issues
      related to the clinical and laboratory diagnosis of upper respiratory tract
      infections. These syndromes occur with great frequency in both adults and
      children and have tremendous economic impact, related not only to lost
      productivity in the workplace but also to the frequent prescription by physicians
      of antibiotics, even when the etiologic agents of infection almost certainly are
      not bacteria. Most of these infections are diagnosed clinically, and specimens
      for microbiological identification are not obtained. Indeed, the difficulty in
      obtaining microbiological specimens that are not contaminated by resident
      colonizing flora often results in laboratory culture reports of dubious clinical
      value. As the authors note, the most standardized procedures are for the
      diagnosis of pharyngitis due to Streptococcus pyogenes. The preferred culture
      methods are reviewed as are the sensitivities, specificities, and limitations of
      rapid direct tests for group A streptococcal antigens. Currently, as the authors
      emphasize, a negative direct test mandates a conventional culture for S.
      pyogenes. More problematic are requests for isolation of other streptococci,
      Haemophilus species, corynebacteria, and gram-negative bacteria. Given limited
      resources, cost-containment imperatives, and the absence of clear evidence that
      these organisms are pharyngeal pathogens associated with important sequelae, my
      laboratory does not attempt to isolate these bacteria unless the ordering
      physician has directly consulted with me (the laboratory director). Carroll and
      Reimer emphasize that nasopharyngeal cultures have no place in the
      microbiological diagnosis of otitis media and that diagnostic tympanocentesis is
      the only procedure for obtaining specimens that yield reliable microbiological
      findings. They also point out the futility of using swabs to obtain material for
      the diagnosis of otitis externa, since the external auditory canal cannot be
      decontaminated sufficiently to obtain a meaningful culture result. Finally, the
      authors address the available methods for obtaining specimens to establish the
      etiology of sinusitis. For microbiological diagnosis, direct antral puncture has
      been the method of choice for many years. However, otorhinolaryngologists now
      obtain many specimens endoscopically. It probably is not possible to obtain
      specimens by this method without contamination by normal upper respiratory flora.
      Thus, results of cultures of endoscopic specimens are more difficult to
      interpret. For patients with complicated illnesses, use of the diagnostic "gold
      standard" of antral puncture, as well as biopsy with histopathologic correlation,
      should be encouraged.

PMID- 8879763
TI  - Increased risk of infection with human immunodeficiency virus type 1 among
      uncircumcised men presenting with genital ulcer disease in Kenya.
AB  - The factors responsible for the explosive spread of human immunodeficiency virus
      type 1 (HIV-1) in sub-Saharan Africa continue to be identified and debated. One
      of the most controversial factors has been male circumcision. This cross
      sectional study was conducted to measure the association between circumcision
      status and infection with HIV-1 among men with genital ulcer disease. Eight
      hundred and ten men participated in the study, of whom 190 (23%) were HIV-1
      positive. A logistic regression model adjusted for behavioral and historical
      showed that HIV-1 positivity was independently associated with being
      uncircumcised (adjusted odds ratio [OR], 4.8; 95% confidence interval [CI], 3.3
      7.2) and with a history of urethral discharge (adjusted OR, 2.0; 95% CI, 1.4
      2.8). This association could not be explained by measures of sexual exposure to
      HIV-1 among this population. Male circumcision should be considered as an
      intervention strategy for AIDS control.

PMID- 8879764
TI  - Efficacy of cefepime in the treatment of infections due to multiply resistant
      Enterobacter species.
AB  - Cefepime is a new cephalosporin with an enhanced antibacterial potency and
      spectrum. More rapid penetration into many gram-negative bacilli, targeting of
      multiple penicillin-binding proteins, and resistance to inactivation by many beta
      lactamases account for its activity against organisms that have developed
      resistance to agents such as ceftazidime, cefotaxime, or ceftriaxone. This study
      identified 16 patients with 17 infections due to Enterobacter species organisms
      with reduced susceptibility or resistance to ceftazidime. Most isolates were
      multiply resistant to other beta-lactam drugs as well, but all were susceptible
      to cefepime. All 17 infections, which included pneumonia, urinary tract
      infection, intraabdominal infection, and bacteremia, responded clinically to
      intravenous cefepime. In particular, cefepime was successfully used in the
      management of cases of chronic infection that had responded poorly to repeated
      therapy with imipenem, aminoglycosides, or ciprofloxacin. Eradication of
      Enterobacter species organisms occurred at 15 (88.2%) of the 17 sites of
      infection. No emergence of resistance to cefepime was noted.

PMID- 8879765
TI  - Prominent osseous and unusual dermatologic manifestations of early syphilis in
      two patients with discordant serological statuses for human immunodeficiency
      virus infection.
AB  - Numerous case reports of atypical and/or severe forms of syphilis in individuals
      coinfected with human immunodeficiency virus (HIV) have led many authorities to
      conclude that HIV exacerbates early syphilitic infection. Herein we report
      prominent osseous and unusual dermatologic manifestations of early syphilis in
      two individuals whose serostatuses for HIV infection were discordant. Our cases
      emphasize the need for caution before conclusions are drawn from anecdotal data
      about the interactions between HIV infection and syphilis.

PMID- 8879766
TI  - Exposure to cytomegalovirus from the donated organ is a risk factor for
      bacteremia in orthotopic liver transplant recipients. Boston Center for Liver
      Transplantation CMVIG Study Group.
AB  - To define predictors of bacteremia and to assess the potential role of exposure
      to cytomegalovirus (CMV) as a risk factor for bacteremia in liver transplant
      recipients, an intention-to-treat analysis of data for 146 orthotopic liver
      transplant recipients who participated in a multicenter, randomized, intervention
      trial was undertaken. Fifty-eight episodes of bacteremia occurred in 40 (27.4%)
      of 146 patients within 1 year after transplantation. Bacteremia was diagnosed a
      median of 39.5 days (range, 1-325 days) after transplantation. One-year mortality
      rates were higher among patients with bacteremia than among those without
      bacteremia (47.5% [19 of 40] vs. 18% [19 of 106], respectively; P = .001). A time
      dependent multivariate analysis of variables that were significantly (P < or =
      .05) associated with bacteremia in the univariate analysis showed that donor CMV
      seropositivity (relative risk [RR], 3.4; 95% confidence interval [CI], 1.6-6.6; P
      = .0005), age of younger than 16 years (RR, 2.6; 95% CI, 1.3-5.2; P < .0059), and
      a major abdominal operation after transplantation excluding retransplantation
      (RR, 3.8; 95% CI, 1.8-8.0; P = .0004) were independently associated with
      bacteremia. These epidemiologic data suggest that exposure to CMV from the
      donated organ is an independent risk factor for bacteremia in orthotopic liver
      transplant recipients.

PMID- 8879768
TI  - Photo quiz. AIDS cholangiography or AIDS sclerosing cholangitis.

PMID- 8879767
TI  - Use of the polymerase chain reaction to detect Legionella DNA in urine and serum
      samples from patients with pneumonia.
AB  - Legionella pneumonia can be difficult to diagnose. Existing laboratory tests for
      detecting Legionella species lack sensitivity or provide only a retrospective
      diagnosis. We used the polymerase chain reaction (PCR) with primers that amplify
      a 104-base pair segment of the coding region of the 5S tRNA gene to detect
      Legionella DNA in urine and serum samples from patients with pneumonia. Stored
      urine and serum samples from patients enrolled in two prospective studies of
      pneumonia were tested. Legionella DNA was detected in urine and/or serum samples
      from 18 (64%) of 28 patients with legionella pneumonia diagnosed by conventional
      tests, but it was not detected in urine or serum samples from 24 patients with
      pneumonia due to other organisms. The sensitivity of PCR improved to 73% if
      testing was restricted to samples taken within 4 days of the onset of symptoms.
      Detection of Legionella DNA in urine and serum promises to be a valuable tool for
      the rapid diagnosis of legionella pneumonia.

PMID- 8879769
TI  - Major differences in the spectrum of gastrointestinal infections associated with
      AIDS in India versus the west: an autopsy study.
AB  - The spectrum of bowel infections in patients with AIDS in India is not well
      characterized. To examine this spectrum of infections, an autopsy study of 49
      subjects was carried out. Multiple sections were obtained from the
      gastrointestinal tract. A pathogenic organism was detected in 25 (71%) of 35
      patients with diarrhea vs. 4 (29%) of 14 patients without diarrhea (P < .01). The
      most frequent pathogen was cytomegalovirus (in 13; 27%), followed by parasites
      (9; 18%), fungi (8; 16%) and Mycobacterium tuberculosis (7; 14%). This is the
      first autopsy study of patients with AIDS in the Indian subcontinent and shows
      important differences in the profile of their opportunistic infections compared
      with those of such patients in the West. These findings will help define the
      optimal diagnostic and therapeutic approaches to patients with AIDS, which, in
      view of the considerable budgetary restrictions in developing countries, should
      be targeted toward the pathogens most frequently identified in such areas.

PMID- 8879770
TI  - Emergence of antibiotic-resistant bacteria in cases of peritonitis after
      intraabdominal surgery affects the efficacy of empirical antimicrobial therapy.
AB  - In cases of community-acquired peritonitis, the adequacy of emprical antibiotic
      treatment has been shown to attenuate mortality and morbidity. The impact of
      empirical antibiotics on the outcome of postoperative peritonitis has never been
      evaluated. This study included 100 consecutively studied patients with
      postoperative peritonitis. The adequacy of emprical treatment was determined by
      means of culture and susceptibility data obtained at the time of reoperation, and
      the effect of such treatment on outcome was evaluated. One hundred resistant
      pathogens were isolated from 70 patients, of whom 45% died; by comparison,
      mortality among those from whom susceptible organisms were isolated was 16% (P <
      .05). Inadequate empirical treatment was administered to 54 patients and was
      associated with poorer outcome (P < or = .05). The outcome of postoperative
      peritonitis is affected by the choice and adequacy of the initial empirical
      antibiotic therapy. Late changes in antibiotic therapy based on culture results
      did not affect outcome when the initial regimen was inadequate.

PMID- 8879771
TI  - Hantavirus pulmonary syndrome, renal insufficiency, and myositis associated with
      infection by Bayou hantavirus.
AB  - Hantaviruses are etiologic agents of hemorrhagic fever with renal syndrome, an
      acute illness characterized by acute renal insufficiency, proteinuria, and
      hemodynamic instability. Recently, a New World form of hantavirus disease,
      hantavirus pulmonary syndrome (HPS), was recognized; in this form, pulmonary
      edema is prominent, but renal insufficiency is generally lacking. HPS cases from
      the southeastern United States may be exceptional in that they have exhibited
      both pulmonary and renal manifestations. One case in Louisiana and one case in
      Florida were linked to infection by the distinct but closely related Bayou and
      Black Creek Canal hantaviruses, respectively. We report a nonfatal case of HPS
      caused by Bayou hantavirus that occurred in eastern Texas. Clinical
      manifestations included pulmonary and renal insufficiency and myositis, which had
      previously been observed in the patient from Florida. The occurrence of
      distinctive clinical abnormalities in HPS cases from the southeastern United
      States supports the concept that there are clinically significant differences
      between western and southeastern forms of HPS.

PMID- 8879772
TI  - Regression of AIDS-related Kaposi's sarcoma during therapy with thalidomide.
AB  - A 14-year-old girl with HIV infection and subcutaneous Kaposi's sarcoma (KS)
      received thalidomide therapy for oral ulcers, resulting in regression of KS
      lesions, disappearance of KS-associated herpesvirus (KSHV) DNA from blood, and
      reduced viral load in tumor tissue. Administration of grauntocyte colony
      stimulating factor resulted in clinical exacerbation of KS and reappearance of
      KSHV DNA in blood.

PMID- 8879773
TI  - Rising incidence of Candida parapsilosis fungemia in patients with hematologic
      malignancies: clinical aspects, predisposing factors, and differential
      pathogenicity of the causative strains.
AB  - Over the years 1983-1994, Candida parapsilosis causes 35 or 138 fungemic episodes
      (24 of 69 candidemias in the last quadriennium) in patients with hematologic
      malignancies who were being treated at a large university hospital in Italy. The
      central venous catheter was usually the source of bloodstream invasion; in most
      cases, the resolution of fungemia in patients receiving antifungal therapy
      required catheter removal. In seven cases, C. parapsilosis fungemia evolved to
      five proven (two cases with endocarditis) and two probable deep-seated
      infections; three of these seven patients died of deep-seated infections. Deep
      seated infection was associated with the detection of a circulating mannoprotein
      antigen of C. parapsilosis but not with in vitro resistance to antifungal agents.
      Almost all fungal isolates produced slime in vitro, but only 34% were pathogenic
      in a model of bloodstream infection in neutropenic mice. The four isolates
      associated with endocarditis or persistent fungemia with multiorgan failure were
      among the most virulent in the model of infection. Overall, our findings
      highlight the role of C. parapsilosis as an agent of fungemia in patients with
      malignant hemopathies.

PMID- 8879774
TI  - Survey of mycoplasmal bacteremia detected in children by polymerase chain
      reaction.
AB  - To determine whether mycoplasmal bacteremia occurs during ordinary or complicated
      diseases due to M. pneumoniae (and if so, how frequently), we used polymerase
      chain reaction (PCR) to detect M. pneumoniae in serum samples. The PCR primers
      used were modified for nested amplification. The genome of this organism was
      detected in 1 of the 25 patients with pneumonia and 10 of the 17 patients without
      pneumonia (P < .001, chi test). The genome was detected more frequently in
      patients who had encephalitis of which the neurological onset was within 7 days
      of the onset of fever rather than later. We hypothesize that mycoplasmal
      bacteremia occurs more frequently than previously appreciated, specifically in
      the absence of pneumonia, and that certain types of complications (e.g.,
      encephalitis of early onset) are associated with its occurrence.

PMID- 8879775
TI  - An unusual case of refractory Campylobacter jejuni infection in a patient with X
      linked agammaglobulinemia: successful combined therapy with maternal plasma and
      ciprofloxacin.
AB  - An unusual hippurate-negative strain of Campylobacter jejuni caused a chronic
      refractory infection in a patient with X-linked agammaglobulinemia; this
      infection persisted for > 2 years despite therapy with various antibiotics and
      immunoglobulins (Igs). To characterize the defense status of this patient,
      several in vitro studies, including those with T cells and polymorphonuclear
      leukocytes (PMNLs), were performed. T cell responses specific for C. jejuni were
      only weak in this patient. Chemiluminescence and bacterial killing studies with
      PMNLs revealed that the bactericidal activity of PMNLs against Campylobacter was
      enhanced more vigorously by maternal serum than by commercial Ig preparations. On
      the basis of these results, combined treatment with ciprofloxacin and maternal
      plasma was initiated, and the C. jejuni infection was rapidly cured. This case
      report shows that in vitro immunologic assays may be useful for characterizing
      immune functions of patients with chronic or refractory C. jejuni infections,
      thus leading to individual treatment strategies.

PMID- 8879776
TI  - Antibiotic susceptibility of multiply resistant Pseudomonas aeruginosa isolated
      from patients with cystic fibrosis, including candidates for transplantation.
AB  - Chronic lung disease caused by antibiotic-resistant Pseudomonas aeruginosa in
      patients with cystic fibrosis (CF) is difficult to treat, especially in those who
      are lung transplantation candidates. Analysis of antibiotic susceptibility and
      synergy studies of 1,296 isolates revealed that 172 (13.3%) were multiply
      resistant (i.e., resistant to two or more classes of anti-Pseudomonas agents).
      beta-Lactam agents (including imipenem and aztreonam) or aminoglycosides
      inhibited only 11% of the multiply resistant strains, while ciprofloxacin
      inhibited 34%. High concentrations of tobramycin and gentamicin (200
      micrograms/mL), achievable by aerosol administration, inhibited 95% of isolates
      and overwhelmed permeability-resistance mechanisms. Antimicrobial pairs tested in
      checkerboard dilutions of clinically achievable drug concentrations inhibited 75%
      of the multiply resistant strains. On average, three additive and 2.4 synergistic
      pairs of antimicrobial agents had activity per strain. Transplantation candidates
      were older than nontransplantation candidates (P = .034), and isolates from
      transplantation candidates were less likely to be inhibited by antibiotic
      combinations (P < .001). Administration of aerosolized aminoglycosides and
      synergy testing of antimicrobial combinations may represent viable therapeutic
      options for patients with CF.

PMID- 8879777
TI  - Mortality due to ventilator-associated pneumonia or colonization with Pseudomonas
      or Acinetobacter species: assessment by quantitative culture of samples obtained
      by a protected specimen brush.
AB  - Ventilator-associated pneumonia (VAP) due to multiresistant pathogens is
      associated with a high death rate. We analyzed the relationship between VAP due
      to Pseudomonas or Acinetobacter species and death by comparing the outcomes for
      patients colonized with these pathogens (bacterial counts of < 10(3) cfu/mL) with
      those for patients with pneumonia due to these pathogens (bacterial counts of >
      or = 10(3) cfu/mL). Samples were obtained systematically with a protected
      specimen brush when pneumonia was suspected. Clinical characteristics at
      admission to our intensive care unit and clinical features at the time of
      suspicion of VAP were not significantly different between colonized patients and
      those with VAP. Mortality rates were 29% among colonized patients and 73% among
      patients with VAP (P < .001). These results demonstrate a relationship between a
      high mortality rate and the development of pneumonia due to multiresistant,
      nonfermenting, gram-negative bacilli ( > or = 10(3) cfu/mL) in the lower airways
      of patients receiving ventilatory support.

PMID- 8879778
TI  - Bacteremia due to Citrobacter species: significance of primary intraabdominal
      infection.
AB  - From 1982 to 1994, 45 patients (1.22 episodes per 10,000 discharged patients)
      were treated for citrobacter bacteremia at National Taiwan University Hospital
      (Taipei). All patients had at least one underlying disease. Citrobacter
      bacteremia most commonly occurred in patients with malignancies (48.9%) or
      hepatobiliary stones (22.2%). Intraabdominal tumors comprised the majority
      (59.1%) of malignancies. Bacteremia commonly originated from sites such as the
      abdominal cavity (51.1%), urinary tract (20%), and lung (11.1%). Polymicrobial
      bacteremia was diagnosed in 15 patients (33.3%); for nine (60%) of these
      patients, the source of the infection was intraabdominal. Prior treatment with a
      third-generation cephalosporin was significantly associated (P < .01) with the
      development of multidrug resistance among the isolates. The mortality associated
      with citrobacter bacteremia was 17.8%. Poor prognostic factors included
      pneumonia, altered mental status on presentation, hypothermia, oliguria, septic
      shock, deterioration in mental status, hyperbilirubinemia, azotemia, and
      thrombocytopenia. Combination therapy, as compared with other regimens, improved
      the outcome of citrobacter bacteremia.

PMID- 8879779
TI  - Flavobacterium indologenes bacteremia: clinical and microbiological
      characteristics.
AB  - To our knowledge, Flavobacterium indologenes has never been reported as a cause
      of bacteremia in humans. F. indologenes bacteremia was diagnosed in 12 patients
      at a tertiary referral center in southern Taiwan between 1 January 1992 and 31
      December 1994. Six of these patients had ventilator-associated pneumonia, two had
      primary bacteremia, and one patient each had pyonephrosis, peritonitis, biliary
      tract infection, and surgical wound infection. Five patients (42%) had
      malignancies, and three (25%) had multiple burns. Polymicrobial bacteremia was
      diagnosed in eight patients (67%). Two (17%) of the patients in this study died;
      both had polymicrobial bacteremia. Antimicrobial susceptibility testing of the
      blood isolates from the 12 patients showed that > 90% of the isolates were
      susceptible to piperacillin, cefoperazone, ceftazidime, and minocycline. The
      chromatograms of esterified fatty acids for the isolates were identical. F.
      indologenes should be considered an etiologic agent of bloodstream infection,
      especially in hospitalized patients with severe underlying diseases.

PMID- 8879781
TI  - Coccidioidomycosis in patients infected with human immunodeficiency virus: review
      of 91 cases at a single institution.
AB  - We retrospectively evaluated the clinical manifestations, diagnosis, treatment,
      and outcome of coccidioidomycosis in 91 patients infected with human
      immunodeficiency virus (HIV) at a single institution. Coccidioidomycosis was the
      AIDS-defining illness in 37 patients. Fever and chills, weight loss, and night
      sweats were the most frequent symptoms. The lung was the most frequently involved
      organ (80%), followed by the meninges (15%). A diffuse reticulonodular infiltrate
      was seen in 59 patients (65%), and 13 (14%) had focal pulmonary disease; for 15
      patients (16%), the chest radiograph was normal. Coccidioidal serologies were
      positive for 60 patients (68%), while for 23% with proven coccidioidomycosis such
      tests were negative Most patients were treated with systemic amphotericin B and
      then an oral azole. The mortality for the whole group was 60%. Patients with
      diffuse pulmonary disease had the highest mortality (68%), with a median duration
      of survival of 54 days (P < .05; 95% confidence interval, 147-175 days). The
      presence of diffuse pulmonary disease and a CD4 lymphocyte count of < 50/microL
      were independent predictors of death. In our experience, coccidioidomycosis is an
      important opportunistic infection that causes substantial morbidity and mortality
      among HIV-infected patients living in an area of endemicity.

PMID- 8879780
TI  - Randomized comparison of amphotericin B deoxycholate dissolved in dextrose or
      Intralipid for the treatment of AIDS-associated cryptococcal meningitis.
AB  - We conducted a randomized, open-labeled clinical trial to compare the
      tolerability and efficacy of amphotericin B deoxycholate, prepared in 5% dextrose
      or Intralipid (Kabi Pharmacia, Saint-Quentin-en-Yvelines, France), in the
      treatment of AIDS-associated cryptococcal meningitis in Burundi. Forty-four
      patients were assigned to receive amphotericin B/dextrose (0.7 mg/[kg.d]) for 14
      days; the dose was then reduced to 1 mg/kg every other day for 28 days (infused
      over 6 hours). Forty-six patients were assigned to receive
      Intralipid/amphotericin B at a 50% higher dosage (1 mg/[kg.d]) for 14 days; the
      dose was then reduced to 1.5 mg/kg every other day for 28 days (infused over 2
      hours). Intralipid significantly decreased the incidence of fever (P = .02) and
      chills (P = .0001) related to the infusion of amphotericin B deoxycholate.
      Analysis of the time to the onset of increased levels of serum creatinine
      (creatinine level, > 150 mumol/L) showed that Intralipid/amphotericin B was more
      nephrotoxic (P = .03). The percentage of patients who were clinically cured or
      had improvement in their conditions and successful mycological outcome was
      similar in both therapeutic groups, but analysis of the time to the first
      negative cerebrospinal fluid culture showed a nearly significant difference that
      favored Intralipid/amphotericin B (P = .07). Intralipid reduced the infusion
      related toxicity of amphotericin B deoxycholate without altering its antifungal
      efficacy but did not confer substantial benefit against renal toxicity that would
      allow the unitary dosage of amphotericin B deoxycholate to be increased safely.

PMID- 8879782
TI  - Achromobacter xylosoxidans bacteremia: report of four cases and review of the
      literature.
AB  - Seventy-seven cases of bacteremia due to Achromobacter xylosoxidans were
      reviewed, and susceptibility studies were performed on 11 clinical isolates of A.
      xylosoxidans. Nosocomial bacteremia was noted in 54 of 77 patients (70%), and 28
      (36%) had infection associated with an outbreak or acquired from a discrete point
      source. The most common underlying illnesses were malignancies (30%) and cardiac
      disease (21%); immunosuppression affected 27%. The most common clinical syndromes
      were primary and catheter-associated bacteremia (19% each) and pneumonia (16%).
      The case-fatality rate was 30%; only 3% of patients with primary or catheter
      associated bacteremia died, but 65% of patients with meningitis, endocarditis,
      and pneumonia died. The case-fatality rate in neonates was 80%. Susceptibility
      studies showed that all strains were resistant to aminoglycosides, most were
      resistant to quinolones, and all were susceptible to broad-spectrum penicillins,
      imipenem, ceftazidime, and trimethoprim-sulfamethoxazole. Two-disk approximation
      and time-kill studies showed synergy or additive effects for the combination of
      gentamicin and piperacillin against most strains.

PMID- 8879783
TI  - Invasive pneumococcal disease: clinical features, serotypes, and antimicrobial
      resistance patterns in cases involving patients with and without human
      immunodeficiency virus infection.
AB  - We reviewed 153 episodes of invasive pneumococcal disease involving 147
      hospitalized patients with and without human immunodeficiency virus (HIV) disease
      to examine and compare epidemiologic and clinical features, capsular serotypes,
      and antibiotic susceptibility patterns. HIV infection was the most common risk
      factor for invasive pneumococcal disease. Pneumococcal disease in HIV-infected
      individuals was characterized by the greater frequency with which pneumonia was
      the source of bacteremia (90% vs. 63%) (P < .01) and an increased recurrence rate
      (15% vs. < 1%) (P < .01). The overall mortality rate was 12% and did not vary by
      HIV serostatus. Capsular-type data were available for 149 episodes; 90% of the
      types were among those found in the polyvalent pneumococcal vaccine. The four
      most common capsular types causing invasive disease were 14, 6b, 9v, and 22f;
      capsular type 9v was significantly more common among HIV-infected patients (P <
      .01). Penicillin-resistant isolates were identified in 7.2% of all cases, and
      their presence did not vary by HIV status; 20% of isolates from cerebrospinal
      fluid were resistant. The majority of the resistant isolates were of capsular
      type 9v. Given the worldwide increase in both HIV and penicillin-resistant
      pneumococcal infections, better preventative and therapeutic strategies are
      greatly needed.

PMID- 8879784
TI  - Interferon alpha for the treatment of chronic hepatitis C in patients infected
      with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group.
AB  - Liver disease secondary to hepatitis C virus (HCV) infection is a rising cause of
      morbidity and mortality among individuals who have been infected parenterally
      with human immunodeficiency virus (HIV) such as injection drug users,
      hemophiliacs, and transfused patients. We analyzed both the efficacy of
      interferon (IFN) alpha therapy in these patients and the predictors of response
      to this agent. A total of 119 patients with chronic hepatitis C (90 of whom were
      infected with HIV and 29 of whom were not) were included in a multicenter,
      prospective, open, nonrandomized observational study. IFN-alpha was given
      subcutaneously in a dosage of 5 million units three times a week during a 3-month
      period; those patients who responded received a dose of 3 million units given
      subcutaneously three times a week for an additional 9 months. One hundred seven
      patients completed the study; the level of aminotransferases returned to normal
      and sera became negative (complete response) for HCV RNA in 26 (32.5%) of 80 HIV
      infected patients and 10 (37.0%) of 27 non-HIV-infected patients (P = .666) after
      completion of the treatment. Two variables were independently associated with a
      response in HIV-infected patients: a CD4+ T lymphocyte count of > 500 x 10(6)/L
      and a baseline HCV viremia level of < 10(7) copies/mL. In the 12 months following
      treatment, relapses occurred in 30.8% of the HIV-infected patients and 12.5% of
      non-HIV-infected patients (P = .403).

PMID- 8879785
TI  - Outcome of medical treatment of bacterial abscesses without therapeutic drainage:
      review of cases reported in the literature.
AB  - The usual treatment of bacterial abscesses, except lung or tubo-ovarian
      abscesses, includes therapeutic drainage. Increasing evidence suggests that some
      abscesses respond to antimicrobial therapy without drainage. To study this issue,
      a MEDLINE search of the literature (1966-1994) was performed for cases of
      bacterial abscess in which treatment without definitive drainage was attempted.
      Four hundred sixty-five cases were identified. The most commonly involved organs
      were the liver, brain, and kidney. The success rate of antimicrobial therapy was
      85.9%. Factors that predicted a less favorable outcome were abscess diameter of >
      or = 5 cm (odds ratio [OR] = 37.7; P = .0003), involvement of > or = 1 organism
      (OR = 5.2; P = .014), presence of gram-negative bacilli (OR = 3.4; P = .022),
      length of therapy of < 4 weeks (OR = 49.1; P < .0001), and use of an
      aminoglycoside as the only active agent (OR = 11.8; P = .008). Many bacterial
      abscesses can be treated without drainage; abscess size, the organisms involved,
      and therapy utilized may influence outcome.

PMID- 8879786
TI  - Medical resolution of proven and putative bacterial abscesses without surgical
      drainage.

PMID- 8879787
TI  - Therapeutic outcome in invasive aspergillosis.
AB  - A review of series of > or = 4 cases of invasive aspergillosis (total, 1,223
      cases) was undertaken to establish the crude mortality and rate of response to
      therapy with amphotericin B in the major at-risk host groups. In association with
      pulmonary, sinus, and cerebral aspergillosis in immunocompromised patients, the
      crude mortality rates were 86%, 66%, and 99%, respectively. No untreated patient
      survived. Among 84 patients treated for 1-13 days, only one survived. Among those
      with invasive pulmonary aspergillosis treated for > or = 14 days, the response
      rates to amphotericin B deoxycholate were 83% (in cases of heart and renal
      transplantation), 54% (leukemia), 33% (bone marrow transplantation) and 20%
      (liver transplantation). Patients with AIDS mostly received both amphotericin B
      and itraconazole, and 37% of those treated for > or = 14 days responded to
      therapy. Substantial variation in outcome from series to series was related to
      underlying disease status, site of disease, and management. Invasive
      aspergillosis remains a devastating opportunistic infection despite current
      treatment.

PMID- 8879788
TI  - "Curbside" consultation and informal communication in medical practice: a
      medicolegal perspective.
AB  - In assessing whether a consulting physician is liable as a result of an informal
      ("curbside") communication, courts examine all of the facts and circumstances to
      determine if a physician-patient relationship existed. Merely answering a
      colleague's question or performing a curbside consultation may not give rise to a
      physician-patient relationship; hence, there is no liability. When duty of care
      can be established, a physician may be liable for medical malpractice. Infectious
      diseases physicians with contractual managed-care roles may have an unrecognized
      duty of care and may actually be at increased risk of liability. Physicians are
      also under duty to act as any reasonably prudent person would act on the basis of
      any foreseeable risk of injury to others. In general, physicians should encourage
      formal consultation when expert advice is sought because a more reliable and
      complete exchange of information occurs before an opinion is rendered in this
      setting. While informal interchange between colleagues is often of educational
      benefit, consultants should avoid giving specific advice about a patient whom
      they have not examined, answer queries in general terms, and consider keeping a
      written record of the interaction.

PMID- 8879789
TI  - Management and outcome of pneumothoraces in patients infected with human
      immunodeficiency virus.
AB  - To better understand the natural history, management, and outcome of
      pneumothoraces in HIV-infected patients, we reviewed hospital charts and chest
      radiographs of HIV-infected adults discharged from the University of Maryland
      Medical Center over a 6-year period. Sixty pneumothoraces occurred in 39
      patients. Twenty-three pneumothoraces resulted from trauma and 37 were
      spontaneous. Thirty-two (86%) of the spontaneous pneumothoraces occurred in
      patients with Pneumocystis carinii pneumonia (PCP). Eight percent of the
      traumatic pneumothoraces in patients who did not have PCP resolved. Patients who
      had pneumothorax as well as PCP were more difficult to manage and had a poorer
      outcome (50% mortality) than those who did not have PCP (25% mortality).

PMID- 8879791
TI  - Use of macrorestriction analysis to demonstrate interhospital spread of
      multiresistant Acinetobacter baumannii in Sao Paulo, Brazil.
AB  - We evaluated the spread of Acinetobacter baumannii strains among three hospitals
      located in Sao Paulo, Brazil. A total of 46 isolates, which were typed by
      chromosomal DNA analysis with use of pulsed field gel electrophoresis (PFGE),
      were tested for susceptibility to the fluoroquinolones, carbapenems,
      aminoglycosides (amikacin), cephalosporins, polymyxin B, and ampicillin/sulbactam
      by means of the broth microdilution method, disk diffusion, and the E-test.
      Isolates with an identical PFGE pattern (pattern B) that were susceptible only to
      carbapenems, polymyxin B, and ampicillin/ sulbactam were recovered in all three
      hospitals. In addition, isolates with PFGE pattern A that were susceptible only
      to polymyxin B and ampicillin/sulbactam were recovered in hospitals 1 and 2. The
      results of our study strongly suggest the interhospital transmission of
      multiresistant epidemic strains of A. baumannii in Sao Paulo. Once in the
      hospital, these strains can disseminate and cause outbreaks with devastating
      consequences.

PMID- 8879790
TI  - Localization of aspergillosis to the central nervous system among patients with
      acute leukemia: report of 14 cases. Gruppo Italiano Malattie Ematologiche
      dell'Adulto Infection Program.
AB  - We retrospectively studied a consecutive series of 100 patients with acute
      leukemia and aspergillosis to evaluate the clinical findings and risk factors for
      colonization of the central nervous system (CNS) by Aspergillus species. The
      diagnosis of CNS aspergillosis was made in 14 patients on the basis of the
      following criteria: neurological signs of CNS involvement (13 of 14 patients);
      cerebral CT scan findings (9 of 12); microbiological findings (6 of 12); and
      histological findings at autopsy (11 of 11). The majority of patients had severe
      neurological complications (i.e., hemiparesis or seizures), due mainly to brain
      abscesses or mycetomas. Autopsies were performed on 11 of 14 patients and
      provided evidence that CNS localization was secondary to invasive aspergillosis;
      in each case, the most likely primary focus of infection was the lung. Although
      all patients had received oral antimycotic prophylaxis and had received timely
      empirical antifungal treatment, they all died within a median time of 5 days from
      the onset of neurological symptoms. Analysis of the characteristics of patients
      with invasive aspergillosis did not reveal any difference between those with CNS
      localization and those without CNS localization.

PMID- 8879792
TI  - Association of acute cystitis with the stage of the menstrual cycle in young
      women.

PMID- 8879793
TI  - Bilateral ureteral obstruction due to Saccharomyces cerevisiae fungus balls.

PMID- 8879794
TI  - Potential role of lamivudine (3TC) in the clearance of chronic hepatitis B virus
      infection in a patient coinfected with human immunodeficiency virus type.

PMID- 8879795
TI  - Optic disk edema as the presenting sign of Lyme disease.

PMID- 8879796
TI  - Fatal toxic epidermolysis induced by zidovudine.

PMID- 8879797
TI  - Prolonged efficiency of secondary prophylaxis with colistin aerosols for
      respiratory infection due to Pseudomonas aeruginosa in patients infected with
      human immunodeficiency virus.

PMID- 8879798
TI  - Intervertebral diskitis caused by Propionibacterium acnes: a report of four
      cases.

PMID- 8879799
TI  - Disseminated Mycobacterium gordonae infection in a patient infected with human
      immunodeficiency virus.

PMID- 8879800
TI  - Fluconazole monotherapy for candidal meningitis in a premature infant.

PMID- 8879801
TI  - Lymphocutaneous sporotrichosis associated with a squirrel bite: case report and
      review.

PMID- 8879802
TI  - Serratia marcescens: a single pathogen in necrotizing fasciitis.

PMID- 8879803
TI  - Resistance to fluconazole and amphotericin B in a patient with AIDS who was being
      treated for candidal esophagitis.

PMID- 8879804
TI  - Moraxella catarrhalis bacteremia as a cause of erythema nodosum.

PMID- 8879805
TI  - Mycobacterium abscessus osteomyelitis following a plantar puncture wound.

PMID- 8879806
TI  - Human granulocytic ehrlichiosis: report of a case in Northern California.

PMID- 8879808
TI  - Relation between the polymerase chain reaction and the indirect fluorescent
      antibody method in the diagnosis of Legionella infection.

PMID- 8879807
TI  - One-year antioxidant supplementation with beta-carotene or selenium for patients
      infected with human immunodeficiency virus: a pilot study.

PMID- 8879809
TI  - Coexistence of pseudogout and arthritis due to Actinobacillus
      actinomycetemcomitans.

PMID- 8879810
TI  - Tumor-like pyomyositis of the thigh caused by Yersinia enterocolitica.

PMID- 8879811
TI  - Therapeutic dilemmas in the care of a human immunodeficiency virus-infected
      patient with vasculitis: case report.

PMID- 8879812
TI  - Hematogenous dissemination of Escherichia coli to a preexistent subdural hematoma
      in a child.

PMID- 8879813
TI  - Disseminated Strongyloides stercoralis infection in an immunocompetent patient.

PMID- 8879814
TI  - Acalculous cholecystitis and microsporidiosis in a patient with AIDS.

PMID- 8879815
TI  - Tricuspid valve endocarditis caused by Streptococcus bovis.

PMID- 8879816
TI  - P2 purinoceptors: historical perspective and classification.
AB  - This article presents an overview that gives some historical perspective to the
      detailed papers at the cutting edge of P2 purinoceptor research that follow. I
      consider the proposal, first put forward by Abbracchio & Burnstock (Pharmacol
      Ther 64:445-475, 1994), that P2 purinoceptors should be regarded as members of
      two main families: a P2X purinoceptor family consisting of ligand-gated ion
      channels, and a P2Y purinoceptor family consisting of G protein-coupled
      receptors. The latest subclasses of these two families (P2X1-4 and P2Y1-5),
      identified largely on the basis of molecular cloning and expression, are tabled.
      Finally, I suggest some future directions for P2 purinoceptor research, including
      studies of the long-term (trophic) actions of purines, the evolution and
      development of purinoceptors and therapeutic applications.

PMID- 8879817
TI  - The diadenosine polyphosphate receptors: P2D purinoceptors.
AB  - Diadenosine polyphosphates-Ap4A, Ap5A and Ap6A-are co-stored in neurosecretory
      vesicles together with ATP and aminergic compounds. They are released from neural
      cells and synaptic terminals in a Ca(2+)-dependent process. Ligand binding and
      displacement experiments carried out with [3H]Ap4A on isolated chromaffin cells
      and synaptosomal preparations result in curvilinear Scatchard plots with Kd
      values close to 0.1 nM for the high-affinity binding sites. Displacement curves
      with two steps are obtained for homologous and heterologous nucleotide ligands;
      the lowest-affinity step exhibits Ki values in the micromolar range for ApnA
      compounds. The high-affinity binding sites were named P2D purinoceptors on the
      basis of their binding characteristics. Single-cell studies in neurochromaffin
      cells indicate the presence of P2X purinoceptors in noradrenergic cells that do
      not respond to Ap4A and in which noradrenaline secretion can be induced by influx
      of extracellular Ca2+. P2Y receptors that respond to ATP analogues and ApnAs are
      present in endothelial cells from adrenal medulla. Those cells that express P2U
      purinoceptors are unresponsive to ApnAs. Ectodiadenosine polyphosphate hydrolases
      with Km values of 0.3 to 2 microM are present in both neural and endothelial
      cells from adrenal medulla. In midbrain synaptic terminals diadenosine
      polyphosphates induce Ca2+ entry from the extracellular medium. The fact that the
      synaptic response is not cross-desensitized by ATP and its non-hydrolysable
      analogues, the non-blocking effect of suramin, and the differential effect of
      Ca2+ channel blockers, together suggest that there are different receptors for
      nucleotides and dinucleotides in rat brain synaptosomes, which we have called P4
      purinoceptors on the basis of functional studies.

PMID- 8879818
TI  - P2T purinoceptors: ADP receptors on platelets.
AB  - ADP acts on platelets via the P2T purinoceptor to cause aggregation, but the way
      in which it does so is not fully understood. Most aggregating agents act via G
      protein-coupled receptors to stimulate phospholipase C (PLC) and so mobilize Ca2+
      via inositol trisphosphate, whereas ADP clearly causes the mobilization of Ca2+
      from internal stores but is only a weak activator of PLC. ADP also inhibits
      adenylate cyclase and it has been suggested that this effect is mediated by a
      different receptor, although evidence from antagonist studies argues against
      this. Studies of Ca2+ influx have shown that ADP is unique in causing a rapid
      influx of Ca2+, and patch-clamp studies have confirmed the activation by ADP of
      non-selective cation channels. This would imply the existence of two ADP
      receptors on platelets, a receptor-operated channel responsible for the rapid
      Ca2+ influx and a G protein-coupled receptor possibly linked to both inhibition
      of adenylate cyclase and mobilization of Ca2+. In this review the structure
      activity relationships for aggregation, inhibition of adenylate cyclase and
      increases in cytoplasmic Ca2+ are summarized, and the relationship between these
      effects discussed.

PMID- 8879819
TI  - P2Z purinoceptors.
AB  - In response to tetra-anionic ATP4-, P2Z receptors signal opening of a non
      selective plasma membrane pore which permits passage across cell membranes of
      ions, nucleotides and other small molecules that are usually membrane impermeant.
      P2Z receptor-induced pores on murine macrophages, macrophage-like cell lines and
      human culture-matured macrophages are permeable to molecules of up to 831 Da. The
      function of P2Z receptors is unknown. Also unknown is whether the binding site
      for ATP4- and the transmembrane pore, the properties that characterize P2Z
      receptors, reside on a single protein or reflect the activities of two or more
      proteins. That ATP(4-) -unresponsive cell lines do not express connexin 43 has
      led Beyer and Steinberg to suggest that opening or surface expression of this gap
      junction protein is induced by P2Z receptors. Xenopus oocytes, injected with cRNA
      transcribed from a pool of 100 cDNA clones isolated from a murine macrophage
      derived cDNA library, and treated with ATP4-, express a non-selective membrane
      conductance characteristic of P2Z receptors. The conductance induced with cRNA is
      smaller than that induced by mRNA from macrophages, suggesting the presence of a
      dominant subunit of a multicomponent receptor in this pool of 100 cDNA clones.

PMID- 8879820
TI  - P2X receptors: a third major class of ligand-gated ion channels.
AB  - Three classes of ligand-gated ion channels are defined by their molecular
      architecture. The first embraces nicotinic, 5-HT3, glycine and GABA receptors.
      The second class contains the glutamate receptors-AMPA, kainate and NMDA types.
      The third class is the P2X receptors for ATP. Current knowledge of the structure
      of these channels is reviewed, and set beside what is known of their basic
      functional properties. The aim of this paper is to consider how our more complete
      understanding of the first two classes of channels might be helpful in forming a
      molecular picture of P2X receptor function.

PMID- 8879821
TI  - P2 purinoceptors and pyrimidinoceptors of catecholamine-producing cells and
      immunocytes.
AB  - ATP is a neuronal (co)transmitter. In addition, both ATP and UTP may exit damaged
      cells and thereby function as extracellular signal molecules. The targets of
      signalling may be the P2 (for ATP and UTP) and P1 (for the degradation product
      adenosine) receptors of, for instance, neurons and immunocytes. UTP may also act
      at separate pyrimidinoceptors. Catecholamine-producing cells (adrenal chromaffin
      cells and peripheral and central noradrenergic neurons) possess P2X and P2Y
      purinoceptors. ATP appears to be a fast excitatory neuro-neuronal transmitter of
      the noradrenergic coeliac and locus coeruleus neurons. This effect is mediated by
      P2X purinoceptors. P2Y purinoceptor-mediated slow excitatory synaptic potentials
      have not yet been demonstrated either in the peripheral or central nervous
      system. On the other hand, after neuronal injury microglial cells (brain
      immunocytes) are engaged in a process called 'synaptic stripping', i.e. the
      displacement of synaptic boutons from the neuronal surface. During this process
      microglial cells are in direct contact with the (co)transmitter ATP. Activation
      of P2X, P2Z and P2Y purinoceptors results in an elevated intracellular Ca2+
      concentration in microglia and macrophages. Various functions of these cells are
      regulated by intracellular Ca2+ (e.g. cytokine production, phagocytosis) and may
      therefore be modulated by nucleotides. Since neuronal damage leads to the
      transformation of microglial cells to macrophages and, at the same time, to the
      efflux of nucleotides from the damaged cells, the requirements for a modulatory
      interaction are fulfilled.

PMID- 8879822
TI  - Trophic actions of extracellular ATP on astrocytes, synergistic interactions with
      fibroblast growth factors and underlying signal transduction mechanisms.

PMID- 8879823
TI  - Trophic roles of P2 purinoceptors in central nervous system astroglial cells.

PMID- 8879824
TI  - Transduction mechanisms of P2Z purinoceptors.
AB  - The ability of extracellular ATP to increase the cation permeability of a variety
      of fresh and cultured cells has been known for decades, but evidence of a
      separate class of P2 purinoceptor, termed P2Z, which mediates this effect has
      only recently been obtained. Several features of the P2Z purinoceptor clearly
      distinguish it from other P2 purinoceptors and show that it is a ligand-gated ion
      channel. P2Z purinoceptors are highly selective for the ATP4- species and
      addition of Mg2+ in excess over ATP closes the channel. The most potent agonist
      is 3'-O-(4-benzoyl)benzoyl ATP which has a 10-fold lower EC50 than ATP. Ca2+ is
      the preferred permeant for the P2Z ion channel although it will pass ions up to
      the size of ethidium(+) (314 Da) in lymphocytes or fura-2 (813 Da) in
      macrophages. The inhibitors of the P2Z purinoceptor or its associated ion channel
      include suramin, amiloride analogues, high extracellular Na+ concentrations and
      2',3'-dialdehyde ATP (oxidized ATP), which blocks irreversibly. Occupancy of P2Z
      purinoceptors stimulates a phospholipase D activity, which may be involved in
      membrane remodelling. Moreover, extracellular ATP causes loss of the glycosylated
      adhesion molecule L-selection from the surfaces of human lymphocytes by enzymic
      cleavage, suggesting a possible role for P2Z purinoceptors in intercellular
      interactions.

PMID- 8879825
TI  - The diverse series of recombinant P2Y purinoceptors.
AB  - A cDNA encoding a P2Y purinoceptor was originally cloned from chick brain and the
      bovine and human homologues have recently been obtained. These are seven
      transmembrane-domain polypetides, i.e. G protein-coupled receptors. When
      activated by agonists, this P2Y receptor mobilizes intracellular Ca2+ and has
      been shown to be coupled to inositol-1,4,5-trisphosphate formation. Its
      pharmacology has been established in several expression systems, using both
      ligand binding and functional responses: 2-methylthioATP has the highest potency
      of nucleotides and derivatives tested, while UTP and alpha, beta-methylene ATP
      are inactive. This was hence assigned as a new subtype of the pharmacologically
      defined P2Y receptors, P2Y1. P2Y1 receptors are exceptionally abundant in the
      brain. A P2U receptor reported by others can be designated P2Y2. Another P2
      receptor subtype, P2Y3, now cloned as a cDNA from the brain and expressed in
      oocytes and in transfected cells, shows a quite different ligand potency profile
      to the first two. A fourth subtype is expressed primarily in certain haemopoietic
      cells and in cardiac muscle. A putative fifth subtype is expressed only in T
      lymphocytes, upon activation. Yet other P2Y subtypes are indicated by recent
      cloning studies. The amino acid sequences of all of these P2 receptors, while
      displaying some homology, are strikingly diverse: they form a separate and
      unusual new family in the G protein-coupled receptor main superfamily.

PMID- 8879826
TI  - P2U purinoceptors: cDNA cloning, signal transduction mechanisms and structure
      function analysis.
AB  - The cloning of a P2U purinoceptor cDNA has made it possible to use molecular
      biological approaches to investigate P2U purinoceptor function. Expression of
      recombinant P2U purinoceptors in mammalian cells lacking endogenous P2U
      purinoceptors has enabled us to characterize the receptor protein and its
      downstream effectors, and has allowed a partial analysis of the role of certain
      amino acid residues in ligand binding. These approaches have placed the
      pharmacological classification of the P2U purinoceptor on a firm molecular
      footing and have generated model systems that can be used to investigate receptor
      ligand binding, regulation and signal transduction.

PMID- 8879827
TI  - Functional properties of native and cloned P2X receptors.
AB  - Electrophysiological experiments on dissociated smooth muscle and neurons have
      revealed three distinct phenotypes of P2X receptor: (1) a rapidly desensitizing,
      beta-methylene ATP-sensitive response typical of most smooth muscle; (2) a non
      desensitizing, alpha,beta-methylene ATP-insensitive response characteristic of
      PC12 phaeochromocytoma cells and rat superior cervical ganglion neurons; and (3)
      a non-desensitizing, alpha, beta-methylene ATP-sensitive response observed in
      sensory neurons. All of these purinoceptors share a similar cationic and high
      Ca2+ permeability and sensitivity to blockade by suramin, Cibacron blue, oxidized
      ATP, pyridoxal-5-phosphate and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic
      acid. Heterologous expression of two forms of cloned P2X receptors (from rat vas
      deferens and PC12 cells) reveals that each cloned receptor can reconstitute
      native responses with remarkable fidelity. Such results suggest that homo
      oligomeric channels may be formed from single subunits of the P2X receptor in
      smooth muscle, PC12 cells and some neurons. The third phenotype observed in
      native cells might result from co-assembly of subunits of the cloned receptors.
      However, co-expression studies show that these two forms of the P2X receptor do
      not heteropolymerize. Therefore, the non-desensitizing, alpha, beta-methylene ATP
      sensitive response observed in sensory neurons may result from a distinct P2X
      receptor or from heteropolymerization of more than one distinct P2X purinoceptor.

PMID- 8879828
TI  - ATP as a co-transmitter with noradrenaline in sympathetic nerves--function and
      fate.
AB  - ATP and noradrenaline are co-stored in synaptic vesicles in sympathetic nerves
      and when co-released act postjunctionally to evoke contraction of visceral and
      vascular smooth muscle. In the original purinergic nerve hypothesis it was
      proposed that ATP would then be sequentially broken down to ADP, AMP and
      adenosine. Although such breakdown can be measured, it is not clear how the time
      scale of breakdown compares with the time-course of the postjunctional actions of
      ATP. We have investigated the role of ectoATPase in modulating purinergic
      neurotransmission in the guinea-pig vas deferens using ARL67156 (formerly
      FPL67516), a recently developed inhibitor of ectoATPase. ARL67156 (1-100 microM)
      potentiated neurogenic contractions in a concentration-dependent manner. Onset of
      potentiation was rapid and the effect reversed rapidly on washout of the drug.
      The effect was also frequency dependent, being greater at lower frequencies. The
      purinergic component of the neurogenic contraction was isolated using the alpha 1
      antagonist prazosin (100 nM) and ARL67156 caused a similar potentiation. ARL67156
      also potentiated contractions evoked by exogenous ATP (100 microM), but had no
      effect on those of the stable analogue alpha, beta-methylene ATP (500 nM). In the
      presence of the P2 purinoceptor antagonist PPADS (100 microM), ARL67156 also had
      no effect on contractions evoked by noradrenaline (10 microM) or KCI (40 mM).
      These results are consistent with an inhibitory action of ARL67156 on ectoATPase
      and suggest that ectoATPase modulates purinergic transmission in the guinea-pig
      vas deferens. When released from sympathetic nerves, ATP acts at the P2X
      purinoceptor, a ligand-gated cation channel, to evoke depolarization and
      contraction. In single acutely dissociated smooth muscle cells of the rat tail
      artery, studied under voltage-clamp conditions, ATP and its analogues evoke an
      inward current, with a rank order potency of 2-methylthioATP = ATP > alpha, beta
      methylene ATP. This is very different from the order of potency for evoking
      contraction in whole vessel rings, which is alpha, beta-methylene ATP > > 2
      methylthioATP > or = ATP. This discrepancy can be explained by a previously
      unrecognized attenuation of the action of ATP and 2-methylthioATP, but not alpha,
      beta-methylene ATP, by ectoATPase in whole tissues.

PMID- 8879829
TI  - ATP release and its prejunctional modulation.
AB  - We studied some properties of the release of noradrenaline and ATP in isolated
      sympathetically innervated tissues. Release was elicited by electric stimulation
      and assessed as overflow of tritiated compounds (after labelling with
      [3H]noradrenaline) and enzymically measured ATP, respectively. Evans blue, which
      inhibits ectonucleotidases, greatly increased the evoked overflow of ATP,
      indicating that a major part of the ATP was metabolized after release. Much of
      the ATP was postjunctional in origin. The neural fraction was isolated when
      postjunctional release was suppressed by prazosin (alpha 1-adrenoceptor
      antagonist) and suramin (P2 purinoceptor antagonist). Comparison of neural ATP
      and [3H]-noradrenaline release showed that prostaglandin E2 reduced the release
      of both co-transmitters to a similar extent. Activation of prejunctional alpha 2
      adrenoceptors, however, preferentially reduced the release of [3H]noradrenaline,
      and activation of prejunctional A1 purinoceptors reduced preferentially the
      release of ATP. Nucleotides such as ATP depressed the release of
      [3H]noradrenaline through two receptors: the well-known prejunctional A1
      receptors and a separate group of prejunctional P2 purinoceptors. P2 antagonists
      increased the release of [3H]-noradrenaline. Overall, the results indicate
      differential storage, release and modulation of release of the two sympathetic co
      transmitters. They also indicate that postganglionic sympathetic axons possess
      receptors for both co-transmitters: alpha 2 and P2 autoreceptors.

PMID- 8879830
TI  - Involvement of distinct receptors in the actions of extracellular uridine
      nucleotides.
AB  - The P2 purinoceptors were initially defined as a family of receptors responsive
      to extracellular adenine nucleotides. In the late 1980s, it became clear that
      extracellular uridine nucleotides are also able to modulate cell function. The
      existence of a nucleotide receptor, common to ATP and UTP, was suggested by
      indirect pharmacological arguments (for instance the lack of additivity and the
      cross-desensitization of the responses to the two nucleotides) and later
      demonstrated by the cloning of a P2U receptor equally responsive to ATP and UTP.
      Vascular endothelial cells are a paradigm of cells on which both ATP and UTP
      exert physiologically relevant effects (stimulation of prostacyclin and nitric
      oxide release). Their response to nucleotides is mediated by two distinct
      receptors, both coupled to phospholipase C: a specific purinoceptor responsive to
      ATP and ADP (P2Y) and a nucleotide receptor responsive to ATP and UTP (P2U). We
      have recently cloned from the human genome a new subtype of receptor (tentatively
      called P2Y4), which is structurally related to the P2U receptor. Functional
      expression revealed its coupling to phospholipase C and its selective
      responsiveness to UTP and UDP. According to the new nomenclature, the P2
      receptors that are coupled to G proteins belong to the P2Y family. It now appears
      that this family encompasses specific purinoceptors (P2Y1, formerly called P2Y),
      nucleotide receptors common to ATP and UTP (P2Y2, previously P2U) and selective
      pyrimidinoceptors (P2Y4). The existence of these pyrimidinoceptors suggests that
      uridine nucleotides may play a role as intercellular mediators, independently
      from adenine nucleotides.

PMID- 8879831
TI  - Features of P2X receptor-mediated synapses in the rat brain: why doesn't ATP kill
      the postsynaptic cell?
AB  - In addition to the widespread excitatory transmission mediated by glutamate
      receptors, P2X receptors also mediate fast excitatory synaptic transmission in
      the brain. The receptors in the brain have some features which are different from
      the more extensively characterized peripheral P2X receptors, possibly suggesting
      a difference in the subunits making up the protein. Perhaps the most notable
      feature of the central receptors is a higher Ca2+ permeability than seen in other
      areas, with a linear current voltage relation. The potential danger to the
      postsynaptic cell of the high Ca2+ permeability of neuronal P2X receptors is
      discussed and various forms of inbuilt features of the synapse and receptors are
      outlined which would combine to protect the neurons from excessive Ca2+ influx
      and consequent danger of cell death. These features include a rapid breakdown of
      transmitter in the cleft, which not only removes the ATP from the cleft quickly,
      but also results in the production of adenosine. Evidence for the interaction of
      ATP-mediated transmission and stimulation of purinoceptors by this adenosine is
      presented from experiments using patch-clamp recording in brain slices. This
      demonstrates an elegant negative feedback mechanism by which a fast excitatory
      transmitter can be inactivated by breakdown to a product which acts as a slow
      inhibitory modulator, controlling release of the original transmitter.

PMID- 8879833
TI  - Challenges in developing P2 purinoceptor-based therapeutics.
AB  - Advances in the molecular cloning, expression and functional characterization of
      the P2 purinoceptor superfamily have provided a wealth of data to support a
      diverse functional role for ATP and related nucleotides in the regulation of
      tissue function. As with other receptor superfamilies, it is likely that distinct
      subtypes of each receptor will subserve discrete functions depending on tissue
      distribution and disease pathophysiology. At the present time, ATP is being
      evaluated as an anticancer agent and as an anaesthesia adjunct whereas UTP is
      studied as a novel treatment for cystic fibrosis. ARL67085 is a potent and
      selective P2T receptor antagonist that has potential as a novel antithrombotic
      agent. The key to exploiting the P2 purinoceptor area to enhance understanding of
      disease aetiology and concurrent therapeutic potential will be to focus efforts
      on the identification of novel pharmacophores that have potent and selective
      interactions with the various receptor subtypes as potential new leads. To this
      end, the use of high-throughput screening in conjunction with combinatorial
      chemical, conventional chemical and natural product library compound sources will
      be critical.

PMID- 8879832
TI  - P2 purinoceptors in the immune system.
AB  - Immune cells express plasma membrane receptors for extracellular nucleotides.
      Both G protein-linked metabotropic and channel-forming ionotropic receptors have
      been described, although no P2 receptor subtype has been cloned from the immune
      system thus far. Metabotropic receptors have been described in human B but not T
      lymphocytes; they have not been found in mouse B and T cells. Ionotropic
      receptors seem to be ubiquitously expressed in the immune system; however, their
      functional properties, if not their pharmacology, appear to be different in
      different immune cells. Human T normal and B leukaemic lymphocytes, human
      macrophages, mouse B and T lymphocytes, mouse microglial and macrophage cells,
      and rat mast cells express ionotropic receptors that recognize ATP4- as the
      preferred ligand, are activated by 3'-O-(4-benzoyl)benzoyl ATP and inhibited by
      oxidized ATP. The pharmacological profile of ionotropic receptors expressed by
      different immune cells is similar, but their permeability properties may be
      different: the pore formed by receptors expressed by macrophages, microglial
      cells and mast cells is typically permeable to charged molecules of molecular
      mass up to 900 Da; on the contrary, that expressed by lymphocytes has a molecular
      cut-off of 200-300 Da. The ionotrpic receptor of immune cells is modulated by
      inflammatory cytokines (e.g. interleukin [IL]-2 and gamma-interferon) and is also
      modulated during monocyte to macrophage differentiation. Transient stimulation of
      the ionotropic receptor of macrophages and microglial cells elicits IL-1 beta
      release. Sustained activation leads to cell death, either by necrosis or
      apoptosis, depending on the given cell type.

PMID- 8879834
TI  - A simple micro-method for determining urea cycle intermediates in blood:
      ornithine, arginine and argininosuccinic acid.

PMID- 8879835
TI  - Serum cortisol binding capacity measured with Concanavalin A-Sepharose in
      patients with a recent inflammatory response.
AB  - It has been suggested that elastase released from activated neutrophils degrades
      cortisol binding globulin. A novel assay for serum cortisol binding capacity was
      therefore devised and applied to assess whether such degradation was evident in
      patients showing a recent inflammatory response as indicated by a raised serum C
      reactive protein. In 49 patients with evidence (C-reactive protein > 50 mg/l) of
      a recent inflammatory response, mean serum cortisol binding capacity (288 nmol/l,
      S.D. = 82.9) was significantly lower (P < 0.05, t test) than in 48 patients (320
      +/- 75.8 nmol/l) whose response was quiescent (C-reactive protein < 6 mg/l) or in
      49 healthy controls (335 +/- 72.4 nmol/l). Four patients with septic shock had
      markedly reduced values (167 +/- 49.9 nmol/l) but low values were not restricted
      to this condition. It is concluded that a population experiencing a recent
      inflammatory response exhibits reduced serum cortisol binding capacity but a role
      for elastase in this process remains to be defined.

PMID- 8879836
TI  - Plasma lipoprotein(a) distribution in the Framingham Offspring Study as
      determined with a commercially available immunoturbidimetric assay.
AB  - The purpose of our research was to evaluate a commercially available, automated,
      immunoturbidimetric assay for lipoprotein(a) (Lp(a)), to determine the
      distribution of Lp(a) in the Framingham Offspring Study population, and to
      determine Lp(a) levels that may be useful for assessing coronary heart disease
      risk. The mean between-run coefficient of variation for this assay was 5.65%.
      Lp(a) concentration was slightly, but significantly, higher in 1949 white women
      (mean +/- S.D. 214 +/- 195 mg/l, median 150 mg/l) than in 1884 white men (mean +/
      S.D. 200 +/- 193 mg/l, median 130 mg/l) participating in Cycle 4 of the
      Framingham Offspring Study (P = 0.0015). Lp(a) values of 300 mg/l and 500 mg/l
      corresponded to approximately the 75th and 90th percentiles, respectively, for
      both men and women, and subjects with concentrations greater than or equal to 500
      mg/l were more likely to have coronary heart disease than subjects with an Lp(a)
      concentration less than 300 mg/l (P < 0.05 for men).

PMID- 8879837
TI  - Enhanced urokinase-type plasminogen activator activity by extracellular matrix
      protein obtained from highly metastatic human lung adenocarcinoma cell line.
AB  - A protein which enhanced urokinase-type plasminogen activator (u-PA) activity was
      purified from the extracts of extracellular matrix of highly metastatic cell line
      HAL-8 derived from human lung adenocarcinoma. The protein showed a single band
      with molecular weight of 65 kDa after the purification by Sephadex G-150 and
      diethylaminoethyl-cellulose followed by reversed phase separation in a high
      performance liquid chromatography system. The purified protein in the immobilized
      conditions enhanced u-PA activity in both plasminogen activation and S-2444
      amidolysis by 4.6- and 2.8-fold increases in the second order rate constants
      (Kcat/K(m)), respectively. This protein was related to neither plasminogen nor
      single-chain u-PA by the immunological studies and with respect to retention time
      on reversed phase analysis. These results suggest that the purified material acts
      as an enhancer of u-PA in extracellular matrix of the cancer cells, inducing an
      effective tissue destruction and cell invasion and possessing a highly metastatic
      potential.

PMID- 8879838
TI  - The effect of toilet sanitizers and detergents on immunological occult blood
      tests.
AB  - Effects of time-releasing toilet bowl sanitizers and their main constituents,
      detergents, on immunological fecal occult blood tests were examined. Six kinds of
      toilet sanitizers and 19 kinds of detergents were included. Patients' fecal
      samples and hemoglobin solutions were measured by means of quantitative
      immunological fecal occult blood tests after being mixed with sanitizer or
      detergent solutions. Marked reduction in hemoglobin concentration or antigenicity
      was observed after the addition of sanitizers or detergents at a final
      concentration of 0.5 g/l. Most of these inhibitory reactions were dose dependent.
      In contrast with the immunological method, the chemical method using o-tolidine
      and guaiac were not affected by the detergents tested. In sampling feces for
      immunological fecal occult blood tests, contact of samples with sanitizer
      solutions should be avoided.

PMID- 8879839
TI  - Biochemical bone markers in patients with multiple myeloma.
AB  - Enhanced bone resorption is a characteristic finding in multiple myeloma (MM).
      The aim of this study was to assess the newer biochemical bone markers in
      patients with myeloma. We studied 17 MM patients--10 males (3 untreated, 5 in
      remission, 2 responding), 7 females (3 in remission, 4 responding) and 15 normal
      controls. Serum bone specific alkaline phosphatase (BSALP), osteocalcin (OC) and
      procollagen type 1 C-terminal peptide (PICP) were determined as markers of bone
      formation, while serum tartrate resistant acid phosphatase (TRAP), urinary
      deoxypyridinoline (Dpyr) and calcium (Ca) were determined as markers of bone
      resorption and the ratio of the levels of bone formation/resorption were
      determined. All markers were measured by enzyme immunoassays (Metra Biosystems),
      except for TRAP by an in-house enzymatic assay and Ca by the cresolphthalein
      method. The Dpyr and Ca were expressed as a ratio to urinary creatinine (Cr)
      excretion. There were significantly higher (i) (Dpyr/Cr)/PICP ratio in male MM
      patients than in controls (P < 0.05); (ii) (a) urinary Dpyr excretion (P <
      0.001), (b) (Dpyr/Cr)/BSALP ratio (P < 0.0001) and (c) (Dpyr/Cr)/PICP (P <
      0.0001) in the untreated male MM subgroup than controls; (iii) (Dpyr/Cr)/BSALP
      ratio (P < 0.05) in the untreated than in the responding male MM subgroup, (iv)
      (Dpyr/Cr)/PICP ratio (P < 0.05) in untreated male patients than in those in the
      remission subgroup. In conclusion, (a) Dpyr is a sensitive marker in assessment
      of bone resorption in MM patients; (b) (Dpyr/Cr)/BSALP or (Dpyr/Cr)/PICP ratio is
      even more sensitive in distinguishing the untreated from the other MM subgroups
      and controls. Therefore, the use of a combination of these markers may have a
      potential role in the management of patients with MM.

PMID- 8879840
TI  - Determination of the activities of the enzyme complexes of the electron transport
      chain in human fibroblasts.
AB  - In order to improve the determination of the activities of the enzyme complexes
      of the electron transport chain (ETC) in fibroblasts, we characterized the
      isolation of mitochondria and measured enzyme activities in mitochondrial
      preparations from fibroblasts of control subjects and patients with suspected
      mitochondrial cytopathy. The isolation procedure yielded 54% of the citrate
      synthase activity in fibroblasts, with a 6-fold enrichment in this mitochondrial
      marker enzyme. The activities of the complexes of the ETC were linear with time
      and with the mitochondrial protein concentration used. The coefficients of
      variation for the enzyme activities determined were in the range of 10% in
      mitochondria from identical fibroblast cultures and between 30 and 70% in
      mitochondria from different fibroblast cultures of the same or of different
      patients. Decreased activities of one or more enzyme complexes (defined as an
      activity below the 95% confidence limit of control values) were found in 15 of 22
      patients investigated. When compared with activities obtained in liver or
      skeletal muscle obtained at autopsy, the results were identical in three but
      different in two patients. The studies show that the activities of the enzyme
      complexes of the ETC can be determined reliably and reproducibly in mitochondria
      isolated from fibroblasts and that the results obtained are potentially useful
      for the diagnosis of mitochondrial cytopathies in patients with suggestive
      symptoms and signs.

PMID- 8879841
TI  - Evaluation of a rapid strip test for insulin-like growth factor binding protein-1
      in the diagnosis of ruptured fetal membranes.
AB  - We evaluated the clinical usefulness of a new bedside test (PROM TEST) for
      insulin-like growth factor binding protein-1 (IGFBP-1) in the detection of
      ruptured fetal membranes (ROM). Cervicovaginal secretion was sampled between 15
      and 37 weeks of gestation from asymptomatic women with apparently intact
      membranes and from women with clinically confirmed ROM, as well as from
      symptomatic women with suspected ROM based on history. IGFBP-1 in samples was
      detected with a dipstick based on immunochromatography. The test result was
      positive in 100% of cases with unequivocal ROM and in 5.3% of cases with
      apparently intact membranes. Furthermore, the PROM TEST was positive in 64 of 181
      patients evaluated for suspected ROM based on history, but in whom the diagnosis
      could not be clinically confirmed at the initial evaluation. Fifty of the 64
      women (78.1%) were delivered prematurely (< 37 weeks). Five of the 117 PROM
      negative patients had elective cesarean section for reasons unrelated to ROM
      before 37 weeks and 10 of the remaining 112 patients (8.9%) had preterm delivery.
      Women with equivocal ROM and a positive test result had a 6.9-fold increased
      relative risk (95% confidence interval 4.2-11.4) of preterm delivery compared
      with women who had a negative result at the time of evaluation. Multiple logistic
      regression including PROM TEST result, contractions, vaginal bleeding and
      cervical changes indicated that a positive PROM TEST result was an independent
      predictor of preterm delivery (P = 0.0001). In summary, a positive PROM TEST
      result identifies ROM with high sensitivity and a negative result effectively
      excludes those with intact membranes. In patients with suspected but clinically
      unconfirmed ROM, the positive test result is associated with increased risk of
      preterm delivery, suggesting that microruptures of fetal membranes can also be
      detected by the PROM TEST.

PMID- 8879842
TI  - Development of a stereospecific radioimmunoassay for the analysis of zopiclone
      and metabolites in urine.
AB  - A sensitive and specific radioimmunoassay has been developed, allowing the
      stereospecific detection of nanogram amounts of (+)- and (-)-enantiomers of
      zopiclone and its major metabolites in urine, without prior extraction or
      purification. Antisera were obtained from two series of four rabbits, immunized
      with optically pure (+)- and (-)-N-hemisuc-cinyldesmethylzopiclone, conjugated to
      bovine serum albumin according to the active ester method. The assay was
      stereospecific, allowing discrimination between the two enantiomers of N
      desmethylzopiclone with mutual cross-reactivities below 2%. Substantial cross
      reaction was observed with the parent compound, although lower than expected, and
      to a lesser extent with the N-oxide metabolite. A selection of hypnotics,
      anxiolytics, antidepressants and some other widely used drugs did not interfere
      with the assay (< 0.1%), when tested at a concentration level of 10
      micrograms/ml. The sensitivity of the assay was 50 pg/ml and 10 pg/ml for the (+)
      and (-)-enantiomers, respectively. The binding assay described here was used to
      evaluate the stereoselective excretion pattern of zopiclone. Analysis of
      cumulative excretion samples from a volunteer revealed a mean metabolic excretion
      ratio (+)/(-) of 2.2, ranging from 1.7 (7 h) to 4.4 (36 h) A mean excretion ratio
      (+)/(-) of 2.5 +/- 1 was calculated after analysis of urine samples from 20
      patients receiving zopiclone as a hypnotic daily.

PMID- 8879843
TI  - Plasma ubiquinol/cholesterol ratios in patients with hyperlipidaemia, those with
      diabetes mellitus and in patients requiring dialysis.
AB  - Plasma ubiquinol was measured in diabetics, patients on haemodialysis (HD)
      therapy, patients maintained by continuous ambulatory peritoneal dialysis (CAPD),
      hyperlipidaemic patients and control subjects. Ubiquinol values were standardized
      using total cholesterol (mumol/mmol). Diabetics, HD and CAPD patients were found
      to have plasma ubiquinol levels which were lower than the control subjects. There
      was no difference in values between the control subjects and hyperlipidaemic
      patients. Values for diabetics with poor metabolic control were similar to those
      with good control, and patients with diabetic complications had values which were
      not significantly different from those for patients with no complications. IDDM
      patients were found to have values which were lower than the control group,
      whereas values for the NIDDM patients were not significantly different. These
      results suggest that increased oxidative stress in certain patient groups may be
      the result of, and/or the cause of, decreased plasma ubiquinol. This could be due
      to increased demand or to decreased ability to regenerate the effective form of
      antioxidant.

PMID- 8879844
TI  - Effects of apo B and apo E gene polymorphisms on lipid and apolipoprotein
      concentrations after a test meal.
AB  - The role of apo B signal peptide and apo E polymorphisms, and individual factors
      (age, sex, etc.) have been investigated on the interindividual variability of the
      postprandial response of 274 subjects ingesting a 1.260-KJ milkshake. The mean
      postprandial response, observed during 4 h, is significantly positive for total
      cholesterol (P < 0.005), LDL-cholesterol (P < 0.0001), triglycerides (P < 0.001),
      apo E (P < 0.0001) and glucose (P < 0.0001), whereas HDL-cholesterol, apo A-I and
      apo B do not present mean postprandial variation. Independently of the mean
      response, some parameters present a large interindividual variability of
      response, which is significantly influenced by cofactors, such as weight or BMI,
      for total and LDL-cholesterol, apo B and apo E or tobacco use for HDL
      cholesterol. Sex has no effect on any lipid levels. Total, LDL-cholesterol and
      apo E responses are correlated with their corresponding fasting values. ApoB
      signal peptide polymorphism is not involved in the postprandial responses,
      whereas apo E polymorphism explains a significant part of the variability of HDL
      cholesterol and apo A-I responses.

PMID- 8879845
TI  - Comparison of circulating phagocyte oxidative activity measured by
      chemiluminescence in whole blood and isolated polymorphonuclear leukocytes.
AB  - The generation of reactive oxygen species (ROS) was measured by chemiluminescence
      (CL) in whole blood and isolated polymorphonuclear leukocytes (PMNLs) in 113
      subjects. There were no differences in ROS production in males and females,
      smokers and non-smokers and no age dependency. A significant correlation was
      found between whole blood CL parameters and between parameters derived from
      isolated cells, but there was no correlation when these parameters were compared
      using isolated PMNLs and whole blood. Variations in serum lipid levels did not
      account for the variability of CL parameters in blood or PMNLs. Both
      methodologies had the same validity in demonstrating priming of phagocytes.
      Zymosan-induced CL was more sensitive in detecting distinct functional states of
      phagocytes than FMLP-induced CL.

PMID- 8879846
TI  - Specificity of hemoglobin A1c measurement by cation exchange liquid
      chromatography. Evaluation of a Mono S column method.
AB  - A method was developed for evaluating the specificity of the ion exchange
      chromatographic HbA1c method by Pharmacia which uses a Mono S column. To
      investigate hemoglobin fractions potentially interfering in HbA1c analysis, the
      chromatographic resolution was enhanced and a peak integration program was used
      which enables the quantitation of overlapping and even shoulder-like peaks.
      Hemoglobin was incubated with glucose in vitro and the chromatograms were
      analyzed before and after incubation. Five minor peaks were detected, close to
      hemoglobin A1c, which could not be conclusively identified as hemoglobins
      previously described. Four of these peaks, the stable ones, were included in the
      fraction of the chromatogram to be measured as HbA1c by the routine method. In
      practice, these peaks comprise 20%-35% of the routine HbA1c result in diabetic
      patients and 30%-45% in non-diabetic subjects. Three of these minor peaks were
      non-dependent on glucose. The chromatography and the peak integration method
      described can also be used to study hemoglobin adducts other than
      glycohemoglobin.

PMID- 8879847
TI  - alpha-Glutathione S-transferase levels in chronic hepatitis C infection and the
      effect of alpha-interferon therapy.
AB  - Serum alpha-glutathione S-transferase (alpha-GST) has been shown to be a
      sensitive marker of liver injury. We compared the relationship of both serum
      alpha-GST and alanine transaminase (ALT) with liver biopsy inflammatory activity
      in patients who had chronic hepatitis C infection (HCV), and examined the effects
      of alpha-interferon therapy on serum alpha-GST and ALT concentrations. Of 32
      patients with chronic HCV infection studied, 17 received alpha-interferon 4.5 MU
      three times per week for 3 months and 15 acted as controls. Liver biopsy just
      prior to treatment was scored for the grade of inflammation (Scheuer histological
      activity index). Serum alpha-GST and ALT were assayed just prior to biopsy and 3
      months later. Neither serum alpha-GST nor ALT levels showed any correlation with
      baseline inflammation on liver biopsy. alpha-Interferon significantly reduced
      serum alpha-GST concentration at 3 months (P = 0.01). ALT fell with treatment but
      not significantly (P = 0.05). Small falls in alpha-GST and ALT were noted in the
      control group, and when these were considered the significance of the changes in
      alpha-GST and ALT with treatment was lost (P = 0.35 and P = 0.09, respectively).
      This study shows that serum alpha-GST is not a useful marker of the degree of
      liver inflammation in chronic HCV infection, though it may be of more value than
      ALT in monitoring response to treatment with alpha-interferon.

PMID- 8879848
TI  - Effect of glucose-6-phosphate dehydrogenase deficiency on reduced and oxidized
      glutathione and lipid peroxide levels in the blood of African-Americans.

PMID- 8879849
TI  - International Federation of Clinical Chemistry. Laboratory assessment of protein
      energy status.
AB  - Laboratory and non-laboratory methods for assessing protein-energy nutritional
      status are reviewed. These are classified into methods for assessing adequacy of
      recent nutritional intake, methods for assessing whole body status, and tests
      which assist in the interpretation of these assessments. Each measurement is
      critically discussed in terms of the rationale for its use, the method of
      analysis, reference values, technical interference and limitations of methods,
      the effects of nutritional status and of other factors on the results, its
      overall usefulness in nutritional assessment, and its value relative to other
      methods. Non-laboratory tests such as dietary assessment, indirect calorimetry,
      functional tests and the many methods available for assessment of body
      composition, including anthropometry, bioelectrical impedance and isotope and
      imaging techniques, are compared with the clinical chemistry tests in common use,
      such as nitrogen balance, plasma protein measurements and urinary markers of
      muscle metabolism. This review provides comprehensive and practical advice on the
      use and limitations of these tests in the assessment of protein-energy
      nutritional status of a group, or of an individual patient.

PMID- 8879850
TI  - Therapeutic recommendations for management of severe hyponatremia: current
      concepts on pathogenesis and prevention of neurologic complications.
AB  - Patients with hyponatremia are exposed to major neurological complications. On
      the one hand hyponatremia itself produces brain edema, increased intracranial
      pressure which potentially leads to subsequent neuropathological sequelae or
      death. On the other hand excessive correction could be followed by development of
      brain demyelinating lesions (central pontine or extrapontine myelinolysis) with
      major disability or fatal outcome. Understanding of brain adaptative mechanisms
      to changes in osmolality largely contributes to explain these neurological
      events. When serum sodium decreases, the brain prevents swelling by extruding
      electrolytes and organic osmolytes, a process almost fully achieved after 48 h.
      Conversely, during subsequent increase in serum sodium, reestablishment of
      intracerebral osmolytes occurs but their reuptake is more delayed (+/- 5 days).
      In both circumstances, these mechanisms can be overwhelmed, leading to brain
      damage. Acute hyponatremia (< 48 h) is generally hospital-acquired, mainly in the
      postoperative state and/or after excessive fluid administration. After abrupt
      fall in serum sodium, seizure, respiratory arrest and coma may develop and these
      manifestations are sometimes explosive in nature. Recognition of even minor
      symptoms is crucial and implies prompt correction. There is generally no risk of
      brain myelinolysis in acute hyponatremia. Some factors are suspected to aggravate
      the prognosis of hyponatremic encephalopathy, including female gender (menstruant
      women), hypoxia and young age. Chronic hyponatremia (> 48 h) usually develops
      outside the hospital and is generally better tolerated. The risks of brain
      myelinolysis can be largely reduced by limiting the correction level to < or = 15
      mEq/1/24 h. However, if necessary, the initial rate of correction can be rapid
      provided that the final correction remains < 15 mEq/1/24 h. However, when other
      recognized risk factors for myelinolysis (hypokalemia, liver disease, poor
      nutritional state, burns) are present, correction should not exceed 10 mEq/1/24
      h. Demyelinization is also observed in hypernatremia but it follows greater (50%)
      increase in serum sodium than from hyponatremic baseline. For symptomatic
      hyponatremia, rapid correction is usually obtained by hypertonic saline (3%)
      infusion. Another option consists in administration of intravenous or oral urea.
      Urea allows a rapid reduction of brain edema and intracranial pressure which is
      followed by subsequent correction of hyponatremia. Experimental data also suggest
      that treatment of hyponatremia with urea is associated with a lower incidence of
      myelinolysis. In hyponatremic patients without symptoms, there is no need for
      rapid correction and the treatment should be more conservative. Close monitoring
      of the serum sodium is indicated initially and if necessary, correction must be
      stopped and diuresis interrupted with dDAVP. Given recent experimental data, in
      patients overly corrected (delta SNa > 15 mEq/1/24 h), the risk of myelinolysis
      could be greatly reduced by rapidly decreasing the serum sodium through hypotonic
      fluids administration and dDAVP.

PMID- 8879851
TI  - Clinical, biochemical and pathological predictors of poor response to intravenous
      cyclophosphamide in patients with proliferative lupus nephritis.
AB  - BACKGROUND: Reports in the literature on the outcome of lupus nephritis (LN)
      treated with intravenous (i.v.) cyclophosphamide have varied considerably.
      Previous studies have suggested that less than 25% of patients with LN will
      progress to end stage renal failure (ESRD) after 5 years. In addition it has been
      reported that serum creatinine and chronic histologic changes on kidney biopsy
      are useful markers of renal prognosis. Whether treatment with cyclophosphamide
      alters the predictive value of these markers in LN patients is not clear. The aim
      of this study was to review our experience of treating a large cohort of patients
      with LN treated with i.v. cyclophosphamide and to identify biochemical and
      histological features at the time renal biopsy which predict outcome in these
      patients. DESIGN: We retrospectively reviewed our experience with 43 consecutive
      patients who met criteria for either World Health Organization (WHO)
      classification III (focal proliferative) or IV (diffuse proliferative) LN and
      were treated with monthly i.v. cyclophosphamide. Biochemical indices of renal
      function and lupus disease activity were recorded. Renal biopsies, performed
      within two months of commencing therapy, were reviewed by two experienced
      pathologists and classified according to WHO classification as well as activity
      and chronicity index. The primary outcome variable for the analysis was the
      development of ESRD. RESULTS: Patients were followed for a mean of 2 years after
      renal biopsy. The mean dose of cyclophosphamide received by patients was 8.3 g.
      One patient died during follow up and 22 (51%) progressed to ESRD. A higher serum
      creatinine (p = 0.003) and higher score for interstitial fibrosis (p = 0.001)
      were associated with shorter renal survival. There was no significant association
      between activity index or its components or in the total chronicity score and
      survival free from the need for dialysis. CONCLUSION: In our experience more than
      half of patients treated with i.v. cyclophosphamide for LN progress to ESRD and a
      high serum Cr and a high degree of interstitial fibrosis on renal biopsy before
      treatment are associated with a worse renal prognosis.

PMID- 8879852
TI  - Comparative value of urinalysis, urine cytology and urine sIL2R in the assessment
      of renal disease in patients with systemic lupus erythematosus (SLE).
AB  - Serial immunological testing has been recently proposed for monitoring patients
      with lupus nephritis as routine serological tests have shown sub-optimal
      correlation with clinical status. To assess the value of urine cytology and urine
      sIL2R in the evaluation of patients with SLE, in particular those with lupus
      nephritis, we conducted a prospective double-blind study of 31 patients with SLE,
      during an 18-month period. A comparison of routine urinalysis with urine cytology
      and urine sIL2R was performed in 84 samples: 15 from patients without a history
      of renal involvement and 69 from patients with a history of renal involvement. A
      high urine cytology score (> or = 6), particularly in the presence of
      lymphoblasts, plasma cells or monocytes, was significantly associated with lupus
      nephritis in relapse. Urine sIL2R levels were significantly elevated during all
      SLE relapses, unrelated to the presence of renal involvement. Fifteen urine
      specimens were obtained at the time of a kidney biopsy: 9 with active lesions and
      6 with inactive renal disease. UC score was 2.0 +/- 1.89 for those with absent
      activity, 8.4 +/- 3.4 for mild activity and 11.0 +/- 2.4 for moderate/severe
      activity (p < 0.001 between active vs inactive disease). No urinalysis parameter
      alone permitted distinguishing the degree of renal disease activity. In the
      subgroup of patients with renal disease urinalysis was overall less accurate than
      urine cytology or urinary sIL2R levels for predicting renal disease activity
      defined by biopsy. Urine cytology and urine sIL2R proved to be reliable measures
      of lupus activity.

PMID- 8879853
TI  - Prospective, randomized, controlled study comparing two dosing regimens of
      gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis.
AB  - Aminoglycosides are drugs of choice for severe gram-negative urinary tract
      sepsis. Recent evidence suggests that they are just as efficacious, but less
      nephrotoxic and ototoxic, if given as a single daily dose rather than in divided
      doses. We considered that a single, large dose of an aminoglycoside followed by
      oral therapy with a different antibiotic might be equally effective and possibly
      less toxic. This randomized, controlled study compared a single large i.v. dose
      (10 mg/kg) of gentamicin (S) with a standard multiple dose regimen (M) of
      gentamicin (2.5 mg/kg i.v. stat and then computer generated divided doses aiming
      for peak and trough concentrations of 8 and 1.5 mg/l respectively) for the
      treatment of patients with suspected acute pyelonephritis requiring
      hospitalization for parenteral antibiotic treatment. All patients were switched
      to oral ciprofloxacin either four hours after the S dose or when clinically
      appropriate in the M regimen. For all patients the total duration of treatment
      was five days. Fifty-three patients (48 women; mean age 32 yr) were enrolled.
      Clinical and bacteriological efficacy could be assessed in 41 patients. Thirteen
      of 16 in the S arm and 24 of 25 in the M arm were clinically cured and the other
      four clinically improved. Fifteen of 16 in the S arm and 23 of 25 in the M arm
      were cured bacteriologically (sterile urine 7-10 days after treatment). In 41
      patients high tone audiometry was carried out before or very soon after the start
      of treatment, and again at the end of treatment. Ototoxicity (> or = 10 dB loss
      in > or = 2 frequencies in both ears) was observed in 3 of 18 in the S group
      (17%) and 7 of 23 in the M group (30%) (NS). Other side-effects and toxicity were
      mild and not different between groups. Substantial cost savings occurred in the S
      group. In summary, a large single dose of gentamicin was comparable in efficacy
      and toxicity to a standard regimen, but cheaper and more convenient to use.

PMID- 8879854
TI  - Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication
      regardless of dose.
AB  - Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide
      spectrum of antimicrobial activity. As a result of the increasing number of AIDS
      patients requiring therapy for Pneumocystis carinii pneumonia, high dose
      trimethoprim-sulfamethoxazole use had dramatically increased. A previously
      unreported and potentially lethal adverse reaction associated with high dose
      trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed.
      Recognition of this potassium disorder led to investigation and description of
      the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia.
      Trimethoprim was found to act like the potassium-sparing diuretic amiloride and
      reduce renal potassium excretion. Subsequent to this work, a handful of cases
      noted the development of hyperkalemia with standard dose trimethoprim
      sulfamethoxazole in elderly patients without evidence of an obvious defect in
      potassium homeostasis. A prospective surveillance study of patients treated with
      standard dose trimethoprim-sulfamethoxazole as compared to similar controls
      treated with other antibiotics confirmed the rise in potassium concentration
      associated with trimethoprim-sulfamethoxazole therapy. Patients with mild renal
      insufficiency were the only group at significant risk for more severe
      hyperkalemia. Hence, trimethoprim-sulfamethoxazole therapy can be complicated by
      hyperkalemia regardless of the dose employed.

PMID- 8879856
TI  - Hemostatic alterations during continuous venovenous hemofiltration in acute renal
      failure.
AB  - In order to determine changes in hemostasis occurring during continuous
      venovenous hemofiltration (CVVH), we made a prospective study of 14 patients with
      acute renal failure. Fibrinopeptide A, thrombin-antithrombin III complex, beta
      thromboglobulin and platelet retention were determined serially. Fibrinopeptide A
      (x +/- SD: 33 +/- 20 ng/ml, ref. < 3.0) and thrombin-antithrombin III complex (11
      +/- 5 ng/ml, ref. 1.0-4.0) were enhanced prior to commencement of treatment but
      showed no further increase during therapy. Platelet retention (Hellem II, ref. 60
      99%) fell from 39 +/- 32% before treatment to 16 +/- 15% after treatment, while
      the beta-thromboglobulin/creatinine ratio (ref. 0.23-0.41) rose from 0.39 +/-
      0.20 to 0.64 +/- 0.44. Via platelet activation, CVVH leads to a reinforcement of
      the existing platelet dysfunction (thrombocytopathy), without influencing
      plasmatic coagulation. In order to analyze the influence of pre-existing
      hemostatic alterations on filter running time during CVVH, 60 patients were
      examined retrospectively in a second study. Filter running time, global
      coagulation tests, fibrinogen, antithrombin III, platelet count and hematocrit
      were registered daily. There was no significant correlation between filter
      running time and fibrinogen concentration, thrombin time, platelet count or
      hematocrit. Apart from filter occlusion, no thrombotic complications were
      observed. The frequency of filter occlusion increased with falling activated
      clotting time (ACT) (p < 0.05). Rising platelet count led to an increase in
      heparin dose (p < 0.05), primarily due to the anti-heparin effect of platelet
      factor 4.

PMID- 8879855
TI  - Trimethoprim-sulfamethoxazole and hypouricemia.
AB  - BACKGROUND: Hypouricemia has been reported in a substantial fraction of patients
      with AIDS and attributed to an HIV-related renal urate transport defect. We
      tested the alternative hypothesis that hypouricemia was associated with the
      administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX). METHODS:
      Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized
      patients with Pneumocystis carinii pneumonia (PCP) with and without HIV
      infection, were abstracted by a blinded reviewer. The primary outcome of interest
      was the percent change in serum uric acid concentration from baseline to hospital
      day 5 +/- 1. RESULTS: Subjects who received TMP-SMX were older (mean age 44.8 vs.
      37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and
      more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than
      those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine,
      sulfadiazine-pyramethamine, or a combination of these agents. The administration
      of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid
      concentration, adjusting for the effects of age, sex, race, HIV antibody status,
      renal function, serum sodium, and the use of diuretics and glucocorticoids (p =
      0.005). CONCLUSION: Among a diverse cohort of hospitalized patients with PCP,
      treatment with high-dose TMP-SMX was strongly associated with a reduction in
      serum uric acid concentration over time.

PMID- 8879857
TI  - Risk modeling in acute renal failure requiring dialysis: the introduction of a
      new model.
AB  - Predicting patient outcome in acute renal failure has become increasingly
      important as technology advances and ethical questions arise concerning life
      supporting therapies. We propose a new model which uses mortality as an endpoint
      and may be applied to the acute renal failure patient in the ICU setting who
      requires dialysis. This model is based on our ICU acute renal failure registry
      and has been prospectively validated for our institution. Our registry for the
      purposes of developing this model consists of data from 512 ICU patients
      requiring acute dialysis from 1988 until 1992. The model was developed by testing
      a variety of potential risk factors for mortality in a univariate analysis
      (Student's t-test and Chi square), and those factors found to be significant (p <
      0.05) were subsequently tested in a multivariate fashion. The factors found
      significant included male gender, respiratory failure requiring intubation,
      hematologic dysfunction (platelet count < 50,000, leukocyte count < 2,500, or
      bleeding diathesis), bilirubin < 2.0 mg/dl, the absence of surgery, serum
      creatinine on the first dialysis treatment day, an increasing number of failed
      organ systems, and an increased BUN from the time of admission. Weights are
      assigned to each variable based on the odds ratio, and a score is generated with
      a range of 0 to 20. The initial data for the registry demonstrates good fit using
      the Hosmer and Lemeshow goodness-of-fit table. The model is next validated in 88
      patients from 1993 through February 1994, then prospectively tested in 35
      additional patients using a standard data collection form, and the model
      continues to demonstrate good fit. Although this model has been prospectively
      validated at our institution, this model or any such predictive model should be
      used with caution if not independently validated at any institution which
      proposes its use.

PMID- 8879858
TI  - Renography in renovascular hypertension.

PMID- 8879859
TI  - Distribution and cellular origin of type III, type IV and type VI collagens in
      tubulointerstitial damage in various renal diseases.

PMID- 8879860
TI  - Recurrent acute pulmonary edema as a presentation of renal artery stenosis in a
      renal transplant patient.

PMID- 8879861
TI  - Postrenal transplant erythrocytosis: a possible role for testosterone,
      angiotensin I-converting enzyme, and N-acetyl-seryl-aspartyl-lysyl-proline: reply
      to Kessler et al.

PMID- 8879862
TI  - High incidence of hiatal hernia in patients with end-stage renal disease.

PMID- 8879863
TI  - Neuro-Behcet's disease.
AB  - We are reporting a case of Behcet's disease without vasculitis, but with acute
      neutrophilic inflammation which involved the brain and other organs. The patient
      exhibited waxing and waning neurological deficits which were unresponsive to
      treatment. The neuroradiologic findings simulated those of multiple sclerosis.
      The neuropathological examination revealed an acute, focal, though disseminated
      encephalitis involving the frontal lobe, internal capsule, basal ganglia,
      cerebellum, and brain stem. The acute inflammation consisted of a neutrophilic
      and eosinophilic infiltration of the perivascular spaces and parenchyma without
      evidence of vasculitis, fibrinoid necrosis, or thrombosis. Cultures and special
      stains for microbial organisms were negative. Ultrastructural examination
      revealed no viral structures or other microorganisms. In situ hybridization for
      Epstein-Barr virus (EBV), herpes simplex virus type I (HSVI), and cytomegalovirus
      (CMV) was negative. In this case, the lack of inflammation in the vessel walls
      points out that the necrotizing lesions in neuro-Behcet's disease need not be the
      result of vasculitis and superimposed thrombosis, but may occur as a result of
      primary, acute neutrophilic inflammation.

PMID- 8879864
TI  - Chloroquine neuromyopathy.
AB  - A 59-year-old woman with rheumatoid arthritis was treated with prednisone and 250
      mg of chloroquine diphosphate (CQ) daily. Though there was improvement in her
      joint symptoms, she began to notice progressive lower limb weakness, later
      extending to the arms and lasting for 2 months. Electromyography showed
      fibrillations, polyphasic potentials and high frequency discharges. Biceps
      brachii biopsy showed that virtually every muscle fiber and multiple small
      vacuoles surrounded by a basophilic rim. There was variation in fiber diameter
      and some fibers were atrophic and angulated. ATPase revealed type grouping.
      Electron microscopy showed, in each muscle fiber, numerous concentric membranous
      bodies, some with curvilinear profiles, beneath the sarcolemma or among the
      myofibrils. Some were also observed in endothelial cells of muscle capillaries.
      CQ was withdrawn, but no significant regression of symptoms had been observed at
      the time follow-up was discontinued. The patient died of cardiac insufficiency
      and bronchopneumonia. The case illustrates a rare complication of CQ therapy of
      rheumatic conditions. It is noteworthy because the drug was administered in
      therapeutic doses and only for a short period. CQ is known to interfere with
      lysosomal function, from which presumably the membranous bodies here described
      originate. Improvement of neuromuscular symptoms has been reported following
      withdrawal of the drug.

PMID- 8879865
TI  - Tl-201 scintigraphy in multivessel exercise-induced variant angina.
AB  - A 53-year-old man presented for evaluation of nocturnal chest pain, consistent
      with angina pectoris. An exercise stress test reproduced his symptoms, however,
      exercise electrocardiograms were nondiagnostic. An exercise-thallium perfusion
      study confirmed vasospasm as the cause. This knowledge guided subsequent
      successful medical therapy.

PMID- 8879866
TI  - First pass Tc-99m MIBI ventriculography in the assessment of left ventricular
      diastolic function. A comparison with Doppler echocardiography.
AB  - Tc-99m MIBI is used for myocardial imaging and first-pass studies. However,
      little is known about its utility in the assessment of left ventricular diastolic
      function. The authors retrospectively compared first pass studies of Tc-99m MIBI
      at rest with Doppler flow velocity measurements to assess left ventricular
      diastolic performance. Thirty-nine patients who had both studies performed within
      48 hours of each other were evaluated. Three indices of diastolic function were
      measured by first pass Tc-99m MIBI ventriculography and Doppler echocardiography:
      1) Time to peak early diastolic velocity; 2) normalized peak filling rate; and 3)
      half filling fraction. The results demonstrated a correlation of 0.82 (P <
      0.001), 0.82 (P < 0.001), and 0.53 (P = 0.001) for the above indices,
      respectively. This study indicates that the indices of left ventricular diastolic
      function by first pass Tc-99m MIBI compare favorably with those derived from
      Doppler flow velocity measurements in which the diagnostic value has been
      previously established. Both methods accurately reflect diastolic flow and may
      facilitate clinical evaluation of diastolic function.

PMID- 8879867
TI  - Scintiscan demonstration of localized bowel loop inflammation. Comparison of Tc
      99m dextran, Tc-99m citrate, and Tc-99m human immunoglobulin G.
AB  - A 60-year-old man with localized small bowel inflammation underwent abdominal
      scintigraphy with Tc-99m human polyclonal immunoglobulin G and two experimental
      inflammation-seeking agents, Tc-99m dextran and Tc-99m citrate. The abnormal loop
      was visualized in all the three studies. Additionally, the Tc-99m dextran study
      revealed exudation and luminal transit of the tracer suggestive of regional
      protein-losing enteropathy. The authors conclude that Tc-99 dextran and Tc-99
      citrate are clinically suitable inflammation-seeking agents that need further
      evaluation, especially for locating abdominal inflammations.

PMID- 8879868
TI  - Bone lymphoma. Comparison of Tl-201 and Ga-67 citrate scintigraphy in assessment
      of treatment response.
AB  - Assessment of response to therapy in patients with lymphoma involving bone can be
      difficult. Of the scintigraphic techniques available, Tl-201 may be the most
      ideal radiopharmaceutical because it reflects tumor burden more accurately than
      either Tc-99m MDP or Ga-67 citrate. We compared serial Tl-201 and Ga-67 citrate
      scintigraphs (24 studies, 12 pairs) in assessing the response to therapy in three
      patients with non-Hodgkin's lymphoma involving bone. In two patients who
      demonstrated a complete remission, uptake of Tl-201 diminished more rapidly and
      returned to normal earlier than did Ga-67 citrate. Tl-201 did not show tumor
      recurrence in the one patient with lesions shown to be Tl-201 negative at
      baseline. Serial studies using Tl-201 may be superior to Ga-67 citrate in the
      evaluation of lymphoma involving bone provided that Tl-201 avidity is
      demonstrated on baseline studies.

PMID- 8879869
TI  - Location of adrenal medullary pheochromocytoma by I-123 metaiodobenzylguanidine
      SPECT.
AB  - This is a retrospective study evaluating the efficacy of SPECT in the location of
      pheochromocytoma. Thirty patients with a suspected pheochromocytoma underwent I
      123 metaiodobenzylguanidine (I-123 MIBG) SPECT 4 and 22 hours after intravenous
      injection of 370 MBq I-123 MIBG. SPECT was compared with planar scintigraphy, CT
      scanning, histology, and clinical course. Twenty-two-hour I-123 MIBG SPECT
      correctly identified 10 patients with adrenal medullary pheochromocytoma and
      correctly excluded pheochromocytoma in 19 patients. The sensitivity of the 22
      hour MIBG SPECT was 1.00 and the specificity was 0.95. The positive predictive
      value was 0.95 and the negative predictive value was 1.00. In 16 patients, planar
      scintigraphy was compared with SPECT. SPECT located normal adrenal glands and
      tumors with greater confidence in three dimensions, but the patients with adrenal
      medullary pheochromocytoma were all correctly identified by planar scintigraphy.
      The results of SPECT and CT agreed in 29 of 30 patients (96.7%). I-123 MIBG SPECT
      for the location of pheochromocytoma has a high sensitivity, specificity, and
      positive and negative predictive values. I-123 MIBG SPECT or CT scanning alone
      were equally good for locating adrenal medullary pheochromocytoma but the
      combination of MIBG SPECT and CT makes it possible to distinguish between
      functioning and nonfunctioning adenomas. I-123 MIBG SPECT may be used alone or in
      combination with planar scintigraphy when three-dimensional location of a lesion
      is wanted.

PMID- 8879870
TI  - Kinetics of Tc-99m sestamibi and Tc-99m tetrofosmin in a case of parathyroid
      adenoma.
AB  - The uptake of Tc-99m tetrofosmin (TF) is reported in a case of parathyroid
      adenoma. A 65-year-old woman was studied on different days with TF, Tc-99m
      sestamibi (MIBI) and Tl-201 chloride (Tl). TF and MIBI injections were preceded
      by oral administration of potassium perchlorate. Clear identification of the
      adenoma was observed in all scans. No further information was obtained using a
      subtraction technique with Tc-99m pertechnetate. Regarding the
      thyroid/parathyroid ratio, different kinetics between TF and MIBI appear to be
      demonstrated. In particular, thyroid washout was observed with MIBI but not with
      TF.

PMID- 8879871
TI  - Monoclonal antibody imaging of occult prostate cancer in patients with elevated
      prostate-specific antigen. Positron emission tomography and biopsy correlation.
AB  - The utility of monoclonal antibody (MAb) imaging for detection of occult
      recurrent prostate cancer was investigated in 14 patients with elevated serum
      prostate-specific antigen at least 3 months after therapy. All were imaged with
      capromab pendetide (CYT-356) and subsequently had biopsies of the prostate bed.
      Ten also had PET scans with F-18 fluorodeoxyglucose. Ten MAb scans were positive
      for tumor in the prostate bed and eight showed lymph node metastases. Six of the
      seven patients with positive biopsies had positive MAb scans, one had a negative
      scan. Three of the seven patients with negative biopsies had negative MAb scans,
      four had positive scans. Of the six patients with positive biopsies who had PET
      scans, one was positive, five were negative. Two of four patients with negative
      biopsies had negative positron emission tomography scans, two were positive. MAb
      imaging is superior to PET scan for identifying recurrent disease in the prostate
      bed. Assuming no false-negative biopsies, the positive predictive values for MAb
      and PET scan are 60% and 33%, negative predictive values are 75% and 29% and
      sensitivities are 86% and 17%. Additional investigation is necessary to determine
      if MAb uptake in lymph nodes is predictive of metastatic disease.

PMID- 8879872
TI  - Renovascular hypertension due to Takayasu's arteritis demonstrated by Tc-99m
      ethylenedicysteine captopril scintigraphy.
AB  - A 34-year-old woman with severe hypertension underwent Tc-99m ethylenedicycteine
      (Tc-99m EC) captopril renal scintigraphy. There was bilateral parenchymal
      retention of the tracer suggesting renal artery stenosis. Angiography confirmed
      bilateral renal artery stenosis and also demonstrated contour irregularities of
      the abdominal aorta, and stenosis in mesenteric and subclavian arteries with
      increased collateral circulation consistent with Takayasu's arteritis. In light
      of this case of renal artery stenosis, it was concluded that Tc-99m EC can be
      used successfully as a potential renal agent in the diagnosis of renal
      involvement in patients with Takayasu's arteritis.

PMID- 8879873
TI  - Ga-67 scintigraphy in pediatric patients. Comparison of extended SPECT of the
      chest and abdomen with planar imaging.
AB  - Ga-67 SPECT has been shown to be more sensitive than planar imaging in several
      pediatric and adult studies. With multidetector SPECT cameras, SPECT imaging of
      multiple sites and volumes rendered images are possible. This study was performed
      to determine if SPECT of the chest, abdomen, and pelvis can be substituted for
      planar imaging of the same body regions. Fifty-one Ga-67 studies in 36 patients
      with lymphoma (29 patients) and inflammation (7 patients) were reviewed. Ga-67
      SPECT of the chest, abdomen, and pelvis was compared with planar images of the
      same body regions. There were 52 abnormal sites on SPECT and 42 on planar
      imaging. Ten sites were positive only on SPECT; five of these sites were seen on
      SPECT because of improved three-dimensional separation of sites of gallium
      uptake. In the limited number of cases in this study, duplicate planar and SPECT
      imaging of the same volume was unnecessary.

PMID- 8879874
TI  - Impact of fluorodeoxyglucose positron emission tomography on the clinical
      management of patients with glioma.
AB  - The past decade has seen the identification of many clinical settings in the
      treatment of primary brain tumors in which information from fluorodeoxyglucose
      positron emission tomography (FDG-PET) might be useful, if not essential, to
      therapeutic formulation. FDG-PET is currently used at referral centers in the
      management of primary brain tumors. The clinical pattern of FDG-PET use was
      assessed and its value compared to other information sources in clinical decision
      making. The clinical records of 75 glioma patients who were evaluated by FDG-PET
      were reviewed. The range of circumstances in which FDG-PET was employed included:
      pretherapeutic baseline studies for monitoring the effect of a therapy (1% of all
      cases), mapping of hypermetabolic regions before surgery or biopsy (2%), mapping
      of hypermetabolic regions before radiotherapy (2%), postsurgical evaluation for
      residual tumor (2%), assessment of the malignancy of a mass as a substitute for
      biopsy (11%), and distinguishing between radiation necrosis and recurrent tumor
      (87%). Other sources of information that contributed to the therapeutic
      management of patients included: gadolinium-enhanced MRI, contrast-CT, and
      clinical findings.

PMID- 8879875
TI  - Lobar extent of pulmonary lymphangitic carcinomatosis. Tl-201 chloride and Tc-99m
      MIBI scintigraphic findings.
AB  - Two cases of histologically proven lobar pulmonary lymphangitic carcinomatosis
      are reported in which well-defined sites of accumulation of Tl-201 and Tc-99m
      MIBI were observed. The combination of Tl-201 and Tc-99m MIBI SPECT can detect
      the extent of pulmonary lymphangitic carcinomatosis.

PMID- 8879876
TI  - Detection of multiple hepatic metastases of gastrinoma not apparent on CT by In
      111 octerotide scintigraphy.

PMID- 8879877
TI  - "Single" abdominal vessel due to clot-filled inferior vena cava.

PMID- 8879878
TI  - Tc-99m DMSA (V) uptake in multiorgan amyloidosis.

PMID- 8879879
TI  - Diffuse visualization of bone marrow with I-123 IMP in a malignant melanoma.

PMID- 8879880
TI  - Thymus accumulation of I-131 after therapeutic dose for thyroid carcinoma.

PMID- 8879881
TI  - Unsuspected pericardial effusion detected by parathyroid scintigraphy with Tc-99m
      MIBI.

PMID- 8879882
TI  - F-18 FDG accumulation in inflamed joints.

PMID- 8879883
TI  - Unexpected detection of an astrocytoma by poorly labeled Tc-99m HMPAO.

PMID- 8879884
TI  - Ga-67 scintigraphy of malignant lymphoma of the uterus.

PMID- 8879885
TI  - Discordance of Tc-99m PMT and Tc-99m GSA in constitutional hyperbilirubinemia.

PMID- 8879886
TI  - Tc-99m sestamibi SPECT imaging of a brain metastasis in a man with lung tumor and
      increased sexual activity.

PMID- 8879887
TI  - Etiologies and sequelae of excessive daytime sleepiness.
AB  - Excessive daytime sleepiness (EDS), the primary complaint of patients seen in
      sleep clinics, affects up to 12% of the general population. The effects of EDS
      can be debilitating and even life threatening. Patients with EDS may exhibit
      psychosocial distress, decreased work or school performance, and increased risk
      for accidents. The differential diagnosis of EDS requires objective assessments,
      such as polysomnography and the Multiple Sleep Latency Test. There are four major
      causes of EDS: (1) central nervous system (CNS) pathologic abnormalities, such as
      narcolepsy and idiopathic CNS hypersomnia; (2) qualitative or quantitative sleep
      deficiencies, such as sleep apnea and insufficient nocturnal sleep; (3)
      misalignments of the body's circadian pacemaker with the environment (eg. jet lag
      or shift work); and (4) drugs, which can increase sleepiness either
      therapeutically or as a side effect. Depending on etiology, management strategies
      for EDS include extension of time in bed, naps, surgery, various medical devices
      (eg, oral appliances, continuous positive airway pressure), and pharmacotherapy.
      Pharmacotherapy is generally achieved with stimulants, such as amphetamine
      sulfate, methylphenidate, and pemoline or newer, safer compounds like modafinil.

PMID- 8879888
TI  - Comparative efficacy of oral and intravenous granisetron for the prevention of
      acute chemotherapy-induced emesis.
AB  - Intravenous 5-hydroxytryptamine3 (5-HT3) receptor antagonists are now established
      antiemetics in the treatment of chemotherapy-induced emesis. For optimal
      convenience and acceptability, oral therapy is desirable. Retrospective
      comparisons indicate that oral granisetron may have an efficacy comparable with
      that of intravenous granisetron. Recent new data are available on the use of
      granisetron in the prophylaxis of acute emesis in randomized, double-masked
      trials. After moderately emetogenic chemotherapy, the optimal regimen appears to
      be 1 mg twice daily, although 2 mg once daily is equally effective. Oral
      granisetron is significantly superior to oral prochlorperazine. After high-dose
      cisplatin chemotherapy, oral granisetron is as effective as metoclopramide plus
      dexamethasone; the addition of dexamethasone further enhances its efficacy. Oral
      granisetron was well tolerated in all these trials. Headache and constipation
      were the most common adverse events, as has been reported for other 5-HT3
      receptor antagonists. No randomized trials of oral-only tropisetron or dolasetron
      have yet been published.

PMID- 8879889
TI  - Changing antipsychotic medication: guidelines on the transition to treatment with
      risperidone. The Consensus Study Group on Risperidone Dosing.
AB  - When treating patients with psychoses, clinicians must often consider changing
      their treatment from one antipsychotic agent to another. The transition may be
      necessary because the patient experiences serious side effects or because the
      existing therapy no longer controls the patient's symptoms. A principal problem
      in changing antipsychotic agents is the potential for withdrawal symptoms
      resulting from discontinuation of the existing therapy. These syndromes can
      manifest as reemergence or worsening of psychosis, rebound or unmasked
      dyskinesia, and cholinergic-rebound symptoms. Withdrawal signs and symptoms may
      include insomnia, nausea, vomiting, anxiety, and agitation. When switching a
      patient to the new antipsychotic agent risperidone, the clinician can keep
      withdrawal symptoms to a minimum by considering the patient's clinical history
      and current status. For some patients, abrupt withdrawal of the current
      antipsychotic may be possible. For others, the dose of the previous medication
      must be gradually reduced before risperidone is initiated. In many cases, the
      transition is best made by overlapping the existing therapy and risperidone.

PMID- 8879890
TI  - Efficacy, tolerability, and effects on quality of life of losartan, alone or with
      hydrochlorothiazide, versus amlodipine, alone or with hydrochlorothiazide, in
      patients with essential hypertension.
AB  - A randomized, double-masked, parallel-group, multicenter clinical trial was
      conducted to compare the efficacy, tolerability, and effects on quality of life
      associated with treatment regimens including the angiotensin II receptor
      antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with
      regimens including the dihydropyridine calcium channel blocker amlodipine with
      HCTZ added as needed. The trial included patients whose sitting diastolic blood
      pressure (SiDBP) measurements were between 95 and 114 mm Hg, inclusive, at
      placebo baseline. Patients were randomized to receive either losartan or
      amlodipine in a double-masked, double-dummy fashion. A 4-week placebo washout
      period was followed by a 12-week active treatment period. Patients in the
      losartan arm (n = 97) were initially given 50 mg of oral (PO) losartan once a day
      (QD); the medication could be titrated to 50-mg losartan/ 12.5-mg HCTZ PO QD
      after 4 weeks, followed by 50-mg losartan plus 25-mg HCTZ PO QD after 8 weeks as
      necessary. Patients in the amlodipine group (n = 93) received 5-mg amlodipine PO
      QD, which could be titrated to 10 mg PO QD after 4 weeks, followed by 10 mg plus
      25-mg HCTZ PO QD after 8 weeks. Medication was titrated upward as necessary to
      achieve trough SiDBP < 90 mm Hg. Efficacy, tolerability, and quality-of-life
      scores were assessed after 12 weeks of therapy with each regimen. Trough SiDBP
      reductions after 4, 8, and 12 weeks of therapy were clinically comparable
      (losartan group: 7.3, 10.4, and 11.1 mm Hg, respectively; amlodipine group: 7.9,
      11.2, and 11.8 mm Hg, respectively). Similar reductions in systolic blood
      pressure were also seen for both treatment groups. The percentage of patients
      reaching goal SiDBP (defined as trough SiDBP < 90 mm Hg or SiDBP > or = 90 mm Hg
      with a > or = 10 mm Hg drop from placebo baseline) was comparable for the two
      groups, with 68% of patients in the losartan group and 71% of patients in the
      amlodipine group reaching goal. Significantly more patients in the amlodipine
      group had drug-related adverse experiences (27% vs 13%). In particular, drug
      related edema was more common in patients receiving the amlodipine regimen than
      in those receiving the losartan regimen (11% vs 1%). Patients in the amlodipine
      arm reported significantly more bother due to edema, regardless of whether edema
      was present at baseline, than did patients in the losartan arm (12% vs 2%),
      although overall quality of life was not different in the two treatment groups.
      This study demonstrates that a regimen of losartan with HCTZ added as needed,
      when compared with a regimen of amlodipine with HCTZ added as needed, provides
      comparable efficacy and superior tolerability and less bother to patients with
      respect to edema.

PMID- 8879891
TI  - Efficacy and safety of cefdinir in the treatment of patients with acute
      bronchitis. The Cefdinir Bronchitis Study Group.
AB  - In this randomized, open-label, dose-comparative study, 18 investigators enrolled
      466 patients with acute bronchitis. Patients were randomly assigned to receive
      either 600 mg of cefdinir once daily (QD) or 300 mg of cefdinir twice daily (BID)
      for 10 days. Both microbiologic and clinical efficacy were assessed at the test
      of-cure visit, 7 to 14 days after therapy stopped. A total of 296 patients were
      classified as assessable at the test-of-cure visit (n = 150 QD, n = 146 BID).
      Eradication rates of baseline pathogens in these assessable patients were similar
      in both groups; the baseline pathogen eradication rate for assessable patients in
      the QD arm was 92%, and that in the BID arm was 93%. Clinical success (cure or
      improvement) in assessable patients was 91% and 93%, respectively. No difference
      was seen in the incidence of adverse events, in the incidence of diarrhea, or in
      the incidence of treatment withdrawals between the two groups. We conclude that
      cefdinir is effective and safe for the treatment of patients with acute
      bronchitis.

PMID- 8879892
TI  - Effectiveness of fluticasone propionate in patients with moderate asthma: a dose
      ranging study.
AB  - This study was undertaken to evaluate the efficacy and safety of fluticasone
      propionate, an inhaled corticosteroid, in adolescents and adults with moderate
      asthma who were previously taking inhaled corticosteroids. After a 2-week, open
      label screening period, a double-masked, randomized, parallel-group, dose-ranging
      study was conducted over 12 weeks in 21 outpatient centers throughout the United
      States. Patients (N = 304) > or = 12 years of age with moderate asthma previously
      treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators
      were enrolled. Patients were assigned to receive placebo or fluticasone
      propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler
      without a spacer device. These doses refer to the amount of fluticasone
      propionate released from the valve of the metered-dose inhaler; the corresponding
      doses released from the activator of the metered-dose inhaler are 88 micrograms,
      220 micrograms, and 440 micrograms, respectively. Between baseline and end point,
      mean values of forced expiratory volume in 1 second decreased 0.31 L in the
      placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100
      micrograms, 250-micrograms, and 500-micrograms fluticasone propionate,
      respectively. The differences between placebo and all treatment groups were
      statistically significant. More patients were withdrawn from placebo (72%) than
      from fluticasone propionate (13% to 16%) because of failure to meet predetermined
      asthma stability criteria. Differences in baseline-to-end point changes in
      morning peak expiratory flow rate, physician overall assessments and patient
      rated assessment of symptoms, and albuterol use for symptom control also
      significantly favored each fluticasone propionate group over placebo. There were
      essentially no differences in efficacy among the three fluticasone propionate
      groups. Treatment-related adverse events occurred in 8% of placebo-treated
      patients and 13% to 15% of fluticasone propionate-treated patients; these events
      were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone
      propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more
      effective than placebo based on maintenance of asthma stability, pulmonary
      function tests, physician and patient assessments, and rescue bronchodilator use.
      No dose-related effects were observed with the dosages of fluticasone propionate
      used in this study.

PMID- 8879893
TI  - Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients
      with advanced prostate cancer.
AB  - Two open-label, multicenter studies were conducted to evaluate the efficacy and
      safety of a long-acting depot formulation of leuprolide acetate (22.5 mg)
      administered intramuscularly every 12 weeks to patients with stage D2 prostate
      cancer. Clinical evaluations were performed every 12 weeks, and serum
      testosterone levels were monitored biweekly or weekly for 24 weeks. Onset of
      castrate levels (< or = 50 ng/dL) of testosterone was achieved within 30 days of
      the initial depot injection in 87 (95%) of the 92 assessable patients enrolled in
      the two studies. Mean testosterone levels remained well within the castrate range
      throughout each dosing interval. Two patients experienced a transient escape
      (testosterone levels > 50 ng/dL on two consecutive determinations). Delay of an
      injection of up to 2 weeks did not have an effect on testosterone suppression: in
      16 patients in whom the depot injection was delayed by 3 to 14 days, testosterone
      values remained within the castrate range. A favorable objective tumor response
      (no progression) to treatment occurred in 85% of the patients. Prostate-specific
      antigen and prostatic acid phosphatase decreased by 50% or more in 96% and 84% of
      patients, respectively, with elevated pretreatment values and at least one
      treatment value. Assessment of local disease status and overall performance
      status showed improvement or stability in most patients. The most common adverse
      events were hot flashes (59%), pain (27%), and testicular atrophy (21%). The 22.5
      mg depot formulation of leuprolide, which acts in a manner similar to the monthly
      7.5-mg depot formulation, was shown to be effective and safe in treating patients
      with advanced prostate cancer.

PMID- 8879894
TI  - The CARE Study: a postmarketing evaluation of ramipril in 11,100 patients. The
      Clinical Altace Real-World Efficacy (CARE) Investigators.
AB  - A postmarketing surveillance study was undertaken to confirm the efficacy and
      safety of the angiotensin-converting enzyme inhibitor ramipril and to extend the
      findings of controlled clinical trials into real-world conditions. A total of
      11,100 patients with mild-to-moderate hypertension treated by primary care
      physicians were enrolled in this 8-week, open-label study. Ramipril was usually
      initiated at a dosage of 2.5 mg once daily and titrated to achieve target blood
      pressure. Efficacy was assessed in 8261 patients for whom blood pressure data
      were recorded after the start of treatment: safety was assessed in all patients.
      Of patients with combined systolic and diastolic hypertension, 86.0% achieved a
      final diastolic blood pressure of < or = 90 mm Hg or a > or = 10 mm Hg decrease
      from baseline; the highest response was seen in elderly patients (87.2%), and the
      lowest response was seen in black patients (81.2%). Of patients with isolated
      systolic hypertension, 70.4% achieved a final systolic blood pressure of < or =
      140 mm Hg or a > or = 20 mm Hg decrease from baseline, including 70.6% of women,
      70.3% of men, and 69.1% of elderly patients; the highest response was seen in
      white patients (71.8%), and the lowest response was seen in black patients
      (64.4%). Adverse events were generally mild; cough (3.0%) was the most frequent.
      Once-daily ramipril was effective and well tolerated during an 8-week period in a
      large, diverse population of patients who had mild-to-moderate hypertension and
      who were treated by primary care physicians.

PMID- 8879895
TI  - Effective administration methods and dosages of interferon therapy for chronic
      hepatitis C.
AB  - The efficacy of interferon alfa (IFN-alpha) was evaluated in 127 hepatitis C
      virus-ribonucleic acid (HCV-RNA)-positive patients with chronic hepatitis C in
      relation to HCV-RNA levels and genotype. Patients were assigned to one of three
      groups. Patients in group A received IFN-alpha daily for 8 weeks (total dose, 336
      million units [MU]); patients in group B received IFN-alpha daily for 4 weeks and
      then intermittently for 20 weeks (total dose, 348 MU); and patients in group C
      received IFN-alpha daily for 2 weeks and then intermittently for 22 weeks (total
      dose, 480 MU). Complete response rates in groups B and C were significantly
      higher than those in group A, regardless of the virus level or genotype. Complete
      response rates in groups B and C were similar, but in patients with a high virus
      level or HCV-RNA genotype II, the partial response rate in group C was
      significantly higher than that in group B. In conclusion, IFN-alpha was more
      effective after daily and then intermittent administration than after daily
      administration only, and a higher daily dose was necessary to be more effective
      in patients with high virus levels or HCV-RNA genotype II.

PMID- 8879896
TI  - Effect of manidipine chloride on various aspects of endocrine function, including
      plasma levels of endothelin-1 and human atrial natriuretic peptide, in patients
      with essential hypertension.
AB  - We assessed various aspects of endocrine function in patients treated for
      essential hypertension with manidipine chloride, a calcium channel blocker, to
      study the effects of this drug on several endogenous humoral factors, including
      human atrial natriuretic peptide (hANP) and endothelin 1 (ET), which influence
      vasoconstriction and blood fluid volume. The study included 19 patients with
      essential hypertension. All patients received manidipine chloride 10 mg/d for 24
      weeks. After treatment blood pressure was normalized in all patients, and there
      were no significant changes in plasma renin activity or blood concentrations of
      vasopressin, hANP, ET, aldosterone, adrenaline, or noradrenaline. There was a
      statistically significant negative correlation between the change in ET levels
      and hANP levels before and after treatment. We also observed a statistically
      significant negative correlation between the change in systolic blood pressure
      caused by manidipine chloride and the change in hANP levels before and after
      treatment. These findings suggest that hANP and ET levels are systematically
      changed by manidipine chloride in patients with essential hypertension. We also
      speculate that changes in blood pressure may be closely related to levels of hANP
      in patients treated with manidipine chloride.

PMID- 8879897
TI  - Efficacy and tolerability of subcutaneous sumatriptan administered using the
      IMITREX STATdose System.
AB  - The efficacy and tolerability of subcutaneous (SC) sumatriptan administered with
      the IMITREX (sumatriptan succinate) STATdose System, which circumvents the need
      for patients or health care professionals to handle a syringe, were evaluated in
      two randomized, double-masked, parallel-group, placebo-controlled, multicenter
      studies. In the clinic, 158 adults with migraine diagnosed according to
      International Headache Society criteria received SC sumatriptan (6 mg) or placebo
      delivered with the IMITREX STATdose System for treatment of a migraine attack. By
      120 minutes after SC dosing, 73% and 79% of sumatriptan-treated patients,
      compared with 28% and 37% of placebo-treated patients in studies 1 and 2,
      respectively, experienced headache relief (a statistically significant
      difference). Clinical disability scores 120 minutes after dosing showed that 75%
      and 85% of sumatriptan-treated patients, compared with 30% and 42% of placebo
      treated patients, were normal or only mildly impaired (a statistically
      significant difference). Similar efficacy rates were observed for nausea,
      phonophobia, and photophobia. No serious or unusual adverse events occurred, and
      no clinically relevant abnormalities in laboratory test values were reported.
      Based on these results, we concluded that SC sumatriptan (6 mg) administered
      using the IMITREX STATdose System is effective for the treatment of migraine. The
      efficacy and tolerability profiles of SC sumatriptan administered with this
      device are similar to those reported for SC sumatriptan administered with a
      conventional syringe.

PMID- 8879898
TI  - Profitability, third-party reimbursement, and access to community pharmacies.
AB  - The purpose of this study was to analyze the extent to which third-party
      reimbursement programs have affected the profitability and availability of
      community pharmacies. Data were taken from records maintained by the Virginia
      Board of Pharmacy and a survey of 177 community pharmacies. Between 1989 and
      1994, 258 outpatient pharmacies opened and 342 closed. Chain and independent
      pharmacies suffered net losses, and supermarket and mass merchandiser pharmacies
      experienced net increases. Few significant changes occurred in the distribution
      of pharmacies over the study period. Fifty-nine chain and independent pharmacies
      and 1 supermarket pharmacy chain provided usable profit and reimbursement data.
      These pharmacies experienced declines in profits and increases in the percentage
      of prescriptions reimbursed by private third-party prescription programs over the
      last several years. Regression analyses indicated that higher ratios of sales of
      private third-party prescriptions to private-pay prescriptions were associated
      with lower profits. All respondents indicated that changes in private third-party
      reimbursement had substantially reduced profits over the past 5 years. The
      results indicate that the growth of private third-party payment has led to lower
      pharmacy profits but has not yet resulted in problems of consumer access.

PMID- 8879899
TI  - The total process cost of parenteral antibiotic therapy: beyond drug acquisition
      cost.
AB  - Intravenous antibiotic therapy represents a considerable expense to hospital
      pharmacy budgets; however, when evaluating the cost of these therapies one needs
      to look beyond acquisition cost and consider the total "process" cost of
      treatment. These additional costs include the personnel time and the materials
      required for drug preparation and administration, maintenance of intravenous
      access, waste disposal, and therapeutic drug monitoring. This paper provides an
      examination of the daily process costs of intravenous therapy with cefazolin,
      cefotaxime, ceftazidime, once-daily ceftriaxone, cefuroxime, or aminoglycoside
      (tobramycin or gentamicin) combination therapy, where the aminoglycoside is given
      once daily or in divided doses. This analysis demonstrates that the costs
      associated with drug preparation and administration can equal or exceed drug
      acquisition costs and are highly dependent on dosing frequency. On this basis,
      ceftriaxone, at $52.21, is the least expensive of these antibiotic regimens in
      terms of total daily process cost, followed by the remaining cephalosporins at
      $53.29 to $94.57, aminoglycoside once-daily combinations at $93.44 to $99.65, and
      aminoglycoside multidose combinations at $103.26 to $111.42, respectively (values
      are given in constant 1995 Canadian dollars). Once-daily ceftriaxone offers the
      potential for cost savings compared with other antibiotic regimens whose
      pharmacokinetics require multiple daily doses, due largely to the reduced
      resources required for ceftriaxone preparation and administration.

PMID- 8879900
TI  - Effect of improved disease management strategies on hospital length of stay in
      the treatment of congestive heart failure.
AB  - Congestive heart failure (CHF) afflicts more than 4.6 million people in the
      United States and increases at a rate of 400,000 newly diagnosed patients per
      year. With more than 1.5 million hospital admissions per year attributed to CHF,
      it is the number one cause of hospitalization. Hospital length of stay (LOS) is
      one key determinant of greater hospital costs and has been the focus in some
      economic studies of CHF patients. In the present study, the potential economic
      benefits for hospitals from the implementation of improved disease-specific
      management programs in the treatment of CHF have been quantified in terms of LOS.
      We estimated the potential effects of disease management on LOS as a residual
      variation across hospitals, controlling for the effects of patient-specific
      characteristics, including severity of disease, health status, insurance status,
      and comorbidities. The study entry criteria and random sample selection yielded
      5242 records for analysis. The average LOS was 7.1 days. The fixed effects or
      disease management practices across hospitals contribute to the explanatory power
      of the model by 4%. The 104 hospital-specific fixed effects measuring the
      potential impact of the differences in disease management relative to the
      reference hospital had values ranging from-3.41 to 4.33 days, for a total spread
      of 7.74 days, even after controlling for all other factors. The analysis suggests
      that the potential gain in profits for hospitals reimbursed on a per-case basis
      may be substantial, if disease management strategies practiced by those hospitals
      that lie to the left of the mean LOS were used by those that lie to the right of
      the mean LOS.

PMID- 8879901
TI  - A cost-minimization analysis of intracervical prostaglandin E2 for cervical
      ripening in an outpatient versus inpatient setting.
AB  - This investigation was undertaken to compare the cost impact of prostaglandin E2
      gel delivered intracervically in an outpatient versus an inpatient setting.
      Eligible pregnant women with a singleton gestation that was beyond 37 weeks
      gestational age and who had an unfavorable cervix (Bishop score < or = 4)
      received a single dose of 0.5 mg of prostaglandin E2 intracervically as an
      outpatient or one or more doses as an inpatient the day before a scheduled
      induction of labor. After gel placement, the outpatient group was monitored for 2
      hours with electronic fetal monitoring before being sent home, while the
      inpatient group was monitored for 2 hours in a labor and delivery unit and then
      sent to the maternity unit overnight. The outpatient (n = 40) and inpatient (n =
      36) groups were not different in terms of maternal age, race, parity, gestational
      age, maternal weight, predose Bishop score, or indication for delivery. Patients
      in the outpatient group incurred significantly less costs ($3835.00 +/- 2172.00
      vs $5049.00 +/- 2060.00) and time (74.4 +/- 33.1 hours vs 100.3 +/- 41.6 hours)
      in the hospital than did patients in the inpatient group. Multiparous patients in
      the outpatient group, compared with those in the inpatient group, spent fewer
      total hours in the hospital (56.6 +/- 19.3 vs 90.3 +/- 41.0 hours) and had a
      lower hospital cost ($2891.00 +/- 1236.00 vs $4704.00 +/- 2100.00). The only
      difference between the nulliparous groups favored outpatient therapy because of
      less intrapartum expenses ($730.00 +/- 405.00 vs $1036.00 +/- 487.00). There were
      no differences between the inpatient and outpatient groups for the frequencies of
      failed inductions, abnormal fetal heart rate patterns, and cesarean sections. No
      adverse maternal or neonatal effects with therapy were encountered in either
      setting. Substantial cost savings were found with prostaglandin E2 therapy in an
      outpatient rather than an inpatient setting for patients who required an
      induction of labor and were candidates for outpatient cervical ripening.

PMID- 8879902
TI  - Pharmacoeconomic analysis of oral therapies for onychomycosis: a US model.
AB  - An evaluation of treatment practices in 13 countries, not including the United
      States, has shown oral terbinafine to be more cost-effective (from a government
      payer perspective) than griseofulvin, itraconazole, and ketoconazole in the
      treatment of onychomycosis of toenails and fingernails. The purpose of this study
      was to evaluate the clinical and economic effects of oral griseofulvin,
      itraconazole, ketoconazole, and terbinafine in the treatment of onychomycosis
      from the perspective of a third-party payer in the United States. A previously
      constructed decision-analytic model evaluating the costs of onychomycosis in 13
      countries outside the United States was updated to determine the costs of
      treating onychomycosis in the United States. Clinical management patterns were
      assessed to identify and quantify physician visits, laboratory tests, and adverse
      drug reaction treatment components for patients with toenail and fingernail
      onychomycosis. A random-effects model meta-analysis of treatment efficacy
      (mycologic cure) and New York Metropolitan Medicare charge data for physician
      fees were used in the treatment model. A sensitivity analysis assessing
      alternative dosing regimens and a rank order stability analysis investigating the
      effects of length of treatment, success rates, relapse rates, and drug
      acquisition costs on overall results were also conducted. Terbinafine had the
      lowest cost per mycologic cure after one treatment regimen for onychomycosis in
      both toenail and fingernail infections ($791.00 and $454.00, respectively). The
      costs of treating toenail and fingernail infections were comparatively higher for
      therapy with itraconazole ($1535.00 and $767.00, respectively), griseofulvin
      ($2385.00 and $837.00, respectively), and ketoconazole ($10,025.00 and $1512.00,
      respectively). As a primary treatment choice, terbinafine also had the lowest
      overall expected cost per patient for both toenail and fingernail infections
      ($977.00 and $550.00, respectively). Griseofulvin had expected costs ($1543.00
      and $822.00, respectively) similar to itraconazole ($1588.00 and $894.00,
      respectively), whereas ketoconazole was the most expensive primary treatment
      choice ($2359.00 and $1287.00, respectively). This study demonstrates that
      terbinafine is an economical and cost-effective treatment for patients with
      dermatophytic onychomycosis, supporting European and Canadian studies. Except for
      the rank order of griseofulvin and itraconazole, sensitivity analyses show that
      these results are fairly stable.

PMID- 8879903
TI  - Efficacy and tolerability of oral ondansetron versus prochlorperazine in the
      prevention of emesis associated with cyclophosphamide-based chemotherapy and
      maintenance of health-related quality of life.
AB  - This study compared the efficacy and tolerability of oral ondansetron (8 mg twice
      daily [BID] for up to 3 days) with those of phenothiazine prochlorperazine (10 mg
      BID for up to 3 days) in 133 cancer patients receiving cyclophosphamide-based
      chemotherapy. In addition, the study evaluated the impact of these treatments on
      patients' health-related quality of life, measured with both the Functional
      Living Index-Cancer and the Functional Living Index-Emesis questionnaires. The
      first dose of study drug was administered 30 minutes before initiation of
      chemotherapy. Patients received a rescue antiemetic at their request or if the
      investigator deemed it necessary. There was a statistically significant
      difference in the number of patients with no emetic episodes over the 3-day study
      period: 60% in the ondansetron group compared with 21% in the prochlorperazine
      group. Twenty-five percent of ondansetron-treated patients compared with 68% of
      prochlorperazine-treated patients experienced three or more emetic episodes,
      rescue medication use, or withdrawal from the study due to emesis or adverse
      events. Among patients with at least one emetic episode, the mean time to emesis
      was significantly longer (13 hours and 37 minutes) in the ondansetron group
      compared with the prochlorperazine group (9 hours and 30 minutes). Nausea and
      appetite scores did not differ significantly between groups. The score on the
      vomiting subscale of the Functional Living Index-Emesis was significantly more
      favorable in the ondansetron group compared with the prochlorperazine group,
      indicating better maintenance of health-related quality of life in ondansetron
      treated patients. Both treatments were well tolerated. The most common
      potentially drug-related adverse event was headache, which occurred in
      significantly more (16%) ondansetron-treated patients compared with
      prochlorperazine-treated patients (3%). The results of this study demonstrate
      that oral ondansetron 8 mg BID for up to 3 days is more effective than
      prochlorperazine 10 mg BID for up to 3 days in the prevention of emesis
      associated with moderately emetogenic chemotherapy.

PMID- 8879904
TI  - Number of symptoms, quantification, and qualification of depression.
AB  - Current classification systems (ICD-10 and DSM-IV) require a quantitative
      criterion for differentiating depressive states, suggesting a correlation between
      the number of symptoms, i.e., the pervasiveness of the syndrome, and the subtype
      of the illness. All the symptoms (within those contained in the diagnostic lists)
      are assumed to have comparable value. To investigate the relevance of the number
      and the type of symptoms reported by 196 patients suffering from depression, we
      compared the symptoms using independent indicators of severity such as the
      Clinical Global Index (CGI) and the social functioning subscale of the Global
      Assessment of Functioning (GAF). A second comparison using the same indicators
      was made between qualitatively distinct categories of DSM-IV and ICD-10 (i.e.,
      melancholic v nonmelancholic, somatic v nonsomatic, and psychotic v
      nonpsychotic). There was evidence that increasing numbers of symptoms actually
      reflect higher levels of severity, but the categorizations that were mainly based
      on qualitative criteria (e.g., melancholia, somatic syndrome, etc.) usually
      attained better discrimination compared with those based on the number of
      symptoms. Moreover, certain symptoms (usually those indicated as endogenous) were
      more likely to be associated with greater severity and pervasiveness. Finally,
      the results clearly showed that different symptoms had different weight in
      establishing the gradient of severity.

PMID- 8879905
TI  - Stealing behavior in eating disorders: characteristics and associated
      psychopathology.
AB  - The objective of the study was to identify, in detail, the characteristics of
      stealing behavior and eventual associated psychopathology in a large group of
      eating-disordered patients. A sample of 155 females meeting DSM-III-R criteria
      for anorexia nervosa (AN) or bulimia nervosa BN completed the Stealing Behavior
      Questionnaire (SBQ) and other self-reporting measures, including the Dissociation
      Questionnaire (DIS-Q). In a subgroup of 80 patients, the SBQ was repeated after 2
      months' treatment. A total of 47.1% of the patients admitted a history of
      stealing; compared with restricting AN (35.3%), the proportion of stealers was
      higher in binge-eating/purging AN (54.8%) and BN (48.7%). The number of patients
      admitting to stealing did not change after 2 months of intensive treatment.
      Compared with other patients, stealers did not differ in signs of general
      psychopathology, but showed more abnormal scores on the DIS-Q (especially "loss
      of control"). The patients whose stealing was clearly related to their eating
      disorder did not show a distinct pattern of eating pathology or associated
      psychopathology. If studied in a systematic way, stealing appears to be more
      frequent than expected; with its relationship to bulimic tendencies and "loss of
      control," it might indicate a more severe (stage of an) eating disorder and, as
      such, deserves more attention from researchers and clinicians than the scarce
      literature is reflecting up to now.

PMID- 8879906
TI  - Anabolic-androgenic steroid use among 133 prisoners.
AB  - We performed a forensic evaluation of a 16-year-old boy convicted of murdering
      his 14-year-old girlfriend while he was taking anabolic steroids. Prior to
      steroid use, he had displayed no features of antisocial personality disorder and
      no criminal record. Prompted by this index case, we interviewed 133 consecutive
      male convicts at the same facility where this boy was incarcerated to assess
      whether steroid use frequently contributed to criminal acts. Two other cases of
      apparent steroid-induced crimes were found in this cohort, suggesting that
      steroid use is an uncommon, though occasionally significant, factor in criminal
      behavior.

PMID- 8879907
TI  - A study of bedside screening procedures for cognitive deficits in chronic
      psychiatric inpatients.
AB  - The Mini-Mental State Examination (MMSE) and the Trail Making Test, part B (TMT
      B) were compared for screening cognitive deficits in a sample of 104 psychiatric
      inpatients at a long-term hospital. The TMT-B classified 84% of the patients as
      impaired. The classic MMSE cutoff score (< or = 23) using serial sevens and
      spelling classified 42% and 24% of the patients respectively, as impaired. The
      new MMSE cutoff classified 71% as impaired. Education, gender, and medication may
      influence impairment when using the MMSE classic cutoff scores. In TMT-B only,
      impairment was influenced by chronicity. The TMT-B was able to distinguish
      patients impaired in the MMSE. The TMT-B, therefore, may be more useful than the
      MMSE to screen for cognitive deficits in chronic psychiatric inpatients.

PMID- 8879908
TI  - Unique patterns of comorbidity in posttraumatic stress disorder from different
      sources of trauma.
AB  - While there are many studies of comorbidity in combat veterans with posttraumatic
      stress disorder (PTSD), studies of PTSD from other sources of trauma (e.g.,
      disasters, crimes, and civil violence) are just beginning to emerge. This is the
      first formal review comparing patterns of comorbidity in PTSD from different
      sources of trauma. Specific attention is given to the relative frequencies of
      substance abuse, depression, generalized anxiety, phobic, panic, somatization,
      psychotic, and personality disorders. The findings reveal that although
      similarities exist, the comorbidity profiles differ according to the type of
      trauma experienced and the population studied. Additionally, the evidence
      suggests that the associated psychiatric disorders are not truly comorbid, but
      are interwoven with the PTSD.

PMID- 8879909
TI  - The relationship of object relations and reality testing deficits to outcome
      status of methadone maintenance patients.
AB  - Impairments in the ability to form and maintain meaningful interpersonal
      relationships and in the ability to distinguish between internal and external
      stimuli are related to an individual's psychological health. The Bell Object
      Relations and Reality Testing Inventory (BORRTI) scores of 146 methadone patients
      were used to evaluate whether transitory (TI) or chronic impairments (CIs) in
      object relations and reality testing were related to more severe drug use, family
      and social problems, psychological distress, as well as more time in treatment,
      seeking additional treatments, or taking psychiatric medication. The results
      showed no significant relationship between BORRTI scores and family or social
      problems, time in treatment, or the months of heroin use between follow-up
      evaluations. However, severity of drug use was related to an impairment in a
      specific dimension of object relations-egocentricity. There was a significant
      relationship between TIs and CIs in object relations and reality testing with
      levels of psychological distress and the likelihood of taking psychiatric
      medication.

PMID- 8879910
TI  - Dissociative experiences and dissociative disorders in acute psychiatric
      inpatients.
AB  - The study attempted to determine the extent of dissociative experiences and the
      prevalence of dissociative disorders (DDs) in a series of acute psychiatric
      inpatients and to correlate these experiences and disorders with some
      sociodemographic, clinical, and historical variables. A total of 207
      consecutively admitted psychiatric inpatients qualified for the study. All were
      examined with the Dissociative Experiences Scale (DES), Structured Clinical
      Interview for DSM-III-R Personality Questionnaire (SCID-II PQ), Parental Bonding
      Instrument (PBI), and Frankfurter Self-Concept Scales (FS). Patients who scored
      greater than 20 on the DES were examined with the Dissociative Disorders
      interview Schedule (DDIS). Altogether, 20% of patients scored greater than 20 on
      the DES. In 5% of the patients, a DD was diagnosed. Significant positive
      correlations were found between DES scores and SCID-II PQ items' frequency with
      regard to all personality disorder types, especially borderline, antisocial,
      schizotypal, and dependent. Less pronounced correlations were found between DES
      and PBI scores, and between DES score and age. Clinical axis I diagnoses did not
      have any pronounced influence on the DES score. In contrast, patients with
      greater proneness to dissociation scored lower on most FS scales. There was a
      tendency for patients with DDs to report childhood abuse more frequently and they
      complained significantly more of somatic symptoms. Dissociative experiences seem
      to be as frequent in Swiss as in North American inpatients, whereas DDs (and
      childhood abuse) were encountered less frequently in Swiss inpatients. A
      correlation seems to exist between dissociation and somatization.

PMID- 8879912
TI  - Lifetime anxiety disorders in women with bulimia nervosa.
AB  - We examined the prevalence and ages at onset of additional childhood and adult
      psychiatric disorders in women with bulimia nervosa and evaluated the
      differential impact of a mood or anxiety disorder on the presentation of bulimia
      nervosa. One hundred fourteen women participating in a clinical trial of
      cognitive-behavioral therapy for bulimia nervosa were assessed at pretreatment
      with structured diagnostic methodology. Although mood disorders were the most
      frequently occurring additional psychiatric disorder (75%), 64% experienced an
      additional anxiety disorder. Age at onset of the anxiety disorders was markedly
      earlier than age at onset of bulimia nervosa or other comorbid conditions.
      Stratification of the sample on the presence of a mood or anxiety disorder
      revealed no differences in the core bulimic symptoms across groups. The presence
      of a mood disorder was associated with greater body dissatisfaction, lower Global
      Assessment of Functioning Scales (GAFS) score, more externalizing disorders of
      childhood, and, as expected, higher Hamilton Depression Rating Scale (HDRS)
      scores. The presence of an anxiety disorder was related to a history of anorexia
      nervosa and earlier age at onset of drug or alcohol dependence. Early-onset
      anxiety disorders are prevalent and may represent one potential pathway to
      bulimia nervosa.

PMID- 8879911
TI  - Prodromal and residual symptoms in bipolar I disorder.
AB  - The objective of the current study was to better understand the nature of
      prodromal and residual symptoms of mania and depression, as reported by patients
      with bipolar I disorder and their family members. Prodromal and residual symptoms
      of mania and depression were elicited from 74 patients with bipolar I disorder.
      In 45 cases, an adult family member provided similar information. Three
      clinicians classified the symptoms into six broad categories: behavioral,
      cognitive, mood, neurovegetative, social, and other. The clinicians also
      categorized symptoms as typical or idiosyncratic. Seventy-eight percent of the
      patients reported prodromal depressive symptoms and 87% reported prodromal manic
      symptoms; greater than half of the patients disclosed residual symptoms of
      depression (54%) and mania (68%). Within each of these four illness categories,
      cognitive symptoms were consistently the most common symptoms reported by
      patients. A substantial number of symptoms were idiosyncratic, particularly those
      reported for residual depression. Agreement between patient and family members on
      reported symptoms was strong for the prodromal phase of both polarities, but less
      so for the residual phases. These preliminary results suggest that patients with
      bipolar I disorder and their family members can identify prodromal and residual
      symptoms, that these symptoms are quite common, and that prodromal symptoms may
      be more prevalent or easier to identify than residual symptoms. Cognitive
      symptoms were consistently the most common symptoms reported by patients.

PMID- 8879913
TI  - Infective endocarditis: update 1996.

PMID- 8879914
TI  - Coronary revascularization in the elderly: Florida multicenter consecutive case
      experience with coronary revascularization in patients age 75 years and older.
      The Program Committee Florida Chapter American College of Cardiology.

PMID- 8879915
TI  - Cardiovascular manifestations of HIV infection.

PMID- 8879917
TI  - Management of atrial fibrillation.

PMID- 8879916
TI  - Screening and treatment recommendations for adults with hypercholesterolemia.

PMID- 8879918
TI  - Cardiovascular disease in the elderly.

PMID- 8879919
TI  - Cerebral embolism.

PMID- 8879920
TI  - PAFS: population-adjusted frequency of sensitization. (I) Influence of sex and
      age.
AB  - Sensitization rates are influenced by sex and age. Crude rates from different
      departments cannot be compared without taking into account these variables.
      However, the influence of sex and age has never been considered quantitatively.
      In 2 hypothetical populations with identical age-specific sensitizations rates,
      but differing age distributions, the influence of age on the overall
      sensitization rate (crude rate) is demonstrated. Furthermore, by an abstract
      reflection on rates, the influence of the proportions of a population category
      (e.g., age) on crude rates is shown (crude rate = sigma (category-specific rate x
      proportion of population in category)). To account for differing distributions of
      sex and age, we propose 2 ways. Sex-specific rates should be presented
      separately. Age-specific rates should be standardized. The standard rate is
      defined as: SR = sigma (category specific rate x proportion of standard
      population in category). Using a standard population with a rectangular structure
      (i.e., with equal proportions in each of the category (age) specific groups), the
      standardized rate is the arithmetic average of the category (age) specific rate.
      Only for simple routine evaluations can a standard population with 2 equal groups
      be used, namely over 39 years and under 40 years. The standardized rate can
      easily be calculated as SR: (positive rate (%under 40 + positive rate (%) over
      39)/2. The general rule should be to use a "rectangular" standard population with
      9 age groups of a 10-year sequence. By using the standardization procedure;
      remaining differences found in different departments can no longer be attributed
      to age and sex. Other factors, such as selection of patients or real
      epidemiological differences, can then be discussed. The application of population
      adjusted frequency of sensitization (PAFS) in any publication on prevalences of
      sensitization is highly recommended.

PMID- 8879921
TI  - Photopatch test reactivity: effect of photoallergen concentration and UVA
      dosaging.
AB  - We have studied the influence of variations in allergen concentration and UVA
      dosaging on the results of photopatch testing with the Scandinavian standard
      photopatch series in 29 patients with photocontact and/or contact allergy to 1 or
      several of the allergens in that series. Photocontact test reactions were more
      sensitive to allergen dilution than plain contact test reactions. Even dilution
      from the standard 5% to 2.5% significantly reduced para-aminobenzoic acid
      photocontact test reactions. Reducing the UVA dose from the standard 5 J/cm2 to
      2.5 or 1 J/cm2 in 2 out of 5 cases turned a significant (++) reaction into a
      doubtful one (+). Increasing the standard UVA dose of 5 J/ cm2 to 20-40 J/cm2
      turned a single + photocontact reaction to trichlorcarbanilide and a single 1 +
      plain contact reaction to chlorhexidine into ++ reactions. In the majority of
      cases, however, neither photocontact nor plain contact test reactions were
      augemented by UVA doses up to 80 J/cm2. We conclude that a UVA dose of 5 J/cm2 is
      sufficient for eliciting photocontact allergic test reactions, and that a
      reduction of either the UVA dose level or the standard allergen concentrations of
      the Scandinavian photopatch test guidelines may cause loss of significant
      photocontact test reactions in a proportion of the cases.

PMID- 8879922
TI  - Delayed-type hypersensitivity to subcutaneous lidocaine with tolerance to
      articaine: confirmation by in vivo and in vitro tests.
AB  - A 43-year-old woman suffered from recurrent localized swellings and an eczematous
      dermatitis starting 1 day after an injection of lidocaine. Intradermal patch and
      lymphocyte transformation tests revealed sensitization to lidocaine and cross
      reactivity to the other aminoacylamide local anesthetics bupivacaine, mepivacaine
      and prilocaine, but not to articane. Contact allergy to the ester local
      anesthetics benzocaine, procaine and tetracaine, the quinoline or aminoacylamide
      cinchocaine, and the preservatives methylparaben and metabisulfite, was excluded.
      A subcutaneous challenge with articaine was well tolerated.

PMID- 8879923
TI  - Occupational dermatoses from exposure to epoxy resin compounds in a ski factory.
AB  - Of 22 workers in a ski factory, occupational allergic contact dermatitis was
      found in 8. 6 were sensitive to epoxy resin compounds, i.e., epoxy resins,
      hardeners or diluents, 1 to cobalt in glass-fiber reinforcements, and 1 to
      formaldehyde in a urea-formaldehyde glue and a lacquer. 4 workers had irritant
      contact dermatitis from epoxy resin compounds, lacquers, sanding dust, or glass
      fiber dust. 3 had contact allergy from a new sensitizer, diethyleneglycol
      diglycidyl ether, in a reactive diluent. Immediate transfer of workers sensitized
      to epoxy resin from epoxy exposure prevents aggravation of their dermatitis and
      broadening of the sensitization to epoxy hardeners, diluents and other compounds.

PMID- 8879925
TI  - Day 4 is better than day 3 for a single patch test reading.
AB  - Readings were performed on day (D) 2, D3 and D4 after application of patch tests
      in 88 patients. 90 patch test reactions in 49 patients were interpreted as
      allergic and of past or present relevance. A single D2 reading detected 58 of the
      allergic reactions with 32 false-negatives and 23 false-positives. A single D3
      reading detected 77 allergic reactions, with 13 false-negatives and 17 false
      positives. A single D4 reading detected 85 allergic reactions, with 5 false
      negatives and 9 false-positives. Therefore, if only a single reading is feasible,
      it is better performed on D4 than on D3.

PMID- 8879924
TI  - Sodium lauryl sulfate effect on the density of epidermal Langerhans cells.
      Evaluation of different test models.
AB  - The effect of different test models for sodium lauryl sulfate (SLS)-induced
      irritant contact dermatitis on epidermal Langerhans cells (LC) numbers was
      examined. Finn Chambers, 8 and 12 mm, containing 15 and 34 or 50 microliters,
      respectively, of 1% aq. solution of SLS were applied to human forearm skin for 48
      h as single or repeated application. The results showed a clear difference
      between the effects with the 2 chamber sizes. The effect of the 8-mm chambers
      could result in increased, unchanged or decreased LC numbers, while 12-mm
      chambers always produced a decrease. These results seem to explain, at least
      partly, the discrepant results reported from various laboratories.

PMID- 8879926
TI  - Allergic contact dermatitis and mercury exanthem due to mercury chloride in
      plastic boots.
AB  - We report a 5-year-old child with previous skin intolerance from Mercurochrome
      (merbromin), who developed a severe allergic contact dermatitis of both feet when
      wearing new polyvinyl chloride (PVC) boots. Within a few days, he developed a
      mercury exanthem involving both legs, groins and lateral parts of the trunk.
      Patch tests showed strong reactions to organic and inorganic mercury compounds,
      in particular to mercury chloride (mercury chloride; HgCl2), 0.01% pet., which
      was identified by atomic absorption spectrometry and polarography in the boots
      worn. New hidden sources of mercury in consumer goods may represent a potential
      source of danger for the future, if its use is not more strictly regulated.

PMID- 8879927
TI  - Elicitation thresholds for thiuram mix using petrolatum and ethanol/sweat as
      vehicles.
AB  - An estimate of amounts of thiurams that may be released from rubber gloves into
      synthetic sweat, has previously been generated. These amounts should be compared
      to elicitation thresholds of patch tests performed with serial dilutions of
      thiuram mix using synthetic sweat as vehicle. Because of solubility properties of
      thiurams in aqueous media, such dilutions cannot directly be prepared. In this
      study, a stem solution was prepared in ethanol. This solution was then further
      diluted with synthetic sweat. Thiuram mix 0.5 w/v% was the most concentrated
      solution in ethanol achievable. The patch test reactions were compared to
      reactions to serial dilutions using petrolatum as vehicle. The experiment
      revealed that endpoint dilution with synthetic sweat was not achieved in this
      study. The threshold for elicitation of positive patch test reactions seemed to
      be lower for ethanol/sweat as vehicle compared to petrolatum: 32% reacted to
      ethanol/synthetic sweat 0.001 mg/cm2 compared to 14% reacting to thiuram in pet.
      0.002 mg/cm2. Based on these results, synthetic sweat may be considered a more
      relevant medium for threshold finding studies than petrolatum. Because of
      expected instability of the aqueous solutions, petrolatum is probably a more
      suitable vehicle for routine testing. The study does not permit final conclusions
      concerning acceptable thresholds for leachable thiurams in rubber gloves, but it
      is likely that an acceptable threshold would be substantially less than 0.001 mg/
      cm2.

PMID- 8879928
TI  - Quantitative aspects of isoeugenol contact allergy assessed by use and patch
      tests.
AB  - The clinical implications of sensitization to the fragrance material isoeugenol
      were studied in 19 subjects. Patch testing with serial dilutions of isoeugenol
      and a repeated open application test (ROAT) were performed. The minimum effect
      level under patch test conditions was below 0.01% isoeugenol in 4/19 (20%) of the
      test subjects. The ROAT was performed with a test solution of 0.2% isoeugenol in
      ethanol, which is the recommended maximum concentration used in perfumes, ethanol
      being applied as vehicle control. 4 weeks was the maximum exposure period. The
      upper arm was used as test site the 1st 14 days and the upper arm as well as the
      neck for the next 14 days. 12/19 (63%) of test subjects had a positive ROAT. 4 of
      the responders (33%) reacted beyond day 7, but none after day 14. Use testing on
      the neck 14 days did not add any further ROAT-positive cases, compared with
      testing on the upper arm. The sensitivity found on patch testing may be a
      guidance for the outcome of use tests with the same compound. In this study, all
      subjects with a positive use test to isoeugenol 0.2% in ethanol also demonstrated
      on patch testing a minimum effect level of 0.2% or lower. Data from serial
      dilution patch and use tests may contribute significant information to assessment
      of the relationship between patch test responses and clinical contact
      hypersensitivity, and thus the safety of allergens used in cosmetics.

PMID- 8879929
TI  - Occupational allergic contact dermatitis due to acrylates in Lodz.
AB  - Among 1619 patients suspected of occupational contact dermatitis examined during
      the years 1990-1994, sensitivity to acrylates was diagnosed in 9 persons (4
      dental technicians, 4 dentists, 1 textile printer). Ethyleneglycol dimethacrylate
      (5 positive patch tests), methyl methacrylate (4), 2-hydroxyethyl methacrylate
      (4) and triethyleneglycol dimethacrylate (4) were the most common sensitizers.
      Comparison of patch test results in dental technicians and dentists indicated
      that dentists were sensitive to a greater number of (meth)acrylate (acrylate and
      methacrylate) allergens and also to certain other allergens (metals and rubber
      additives). Dental technicians were sensitive almost exclusively to
      methacrylates, while the textile printer only to acrylates.

PMID- 8879931
TI  - Fixed drug eruption induced by ofloxacin.

PMID- 8879930
TI  - Natural ingredients based cosmetics. Content of selected fragrance sensitizers.
AB  - In the present study, we have investigated 42 cosmetic products based on natural
      ingredients for content of 11 fragrance substances: geraniol, hydroxycitronellal,
      eugenol, isoeugenol, cinnamic aldehyde, cinnamic alcohol, alpha-amylcinnamic
      aldehyde, citral, coumarin, dihydrocoumarin and alpha-hexylcinnamic aldehyde. The
      study revealed that the 91% (20/22) of the natural ingredients based perfumes
      contained 0.027%-7.706% of 1 to 7 of the target fragrances. Between 1 and 5 of
      the chemically defined synthetic constituents of fragrance mix were found in 82%
      (18/22) of the perfumes. 35% (7/20) of the other cosmetic products (shampoos,
      creams, tonics, etc) were found to contain 0.0003-0.0820% of 1 to 3 of the target
      fragrances. Relatively high concentrations of hydroxycitronellal, coumarin,
      cinnamic alcohol and alpha-amyl cinnamic aldehyde were found in some of the
      investigated products. The detection of hydroxycitronellal and alpha
      hexylcinnamic aldehyde in some of the products demonstrates that artificial
      fragrances, i.e., compounds not yet regarded as natural substances, may be
      present in products claimed to be based on natural ingredients.

PMID- 8879932
TI  - Contact allergy to erythromycin.

PMID- 8879933
TI  - The murine local lymph node assay: search for an alternative, more adequate,
      vehicle than acetone/olive oil (4:1).

PMID- 8879934
TI  - Trichloroethylene and concomitant contact dermatitis in an art painter.

PMID- 8879935
TI  - Hand involvement in allergic contact dermatitis from mercaptobenzothiazole in
      shoes.

PMID- 8879936
TI  - Oral challenge with parabens in paraben-sensitive patients.

PMID- 8879937
TI  - Contact dermatitis from cotoneaster.

PMID- 8879938
TI  - Allergic contact dermatitis from 3-(alpha-methoxy) methylenebenzofuran-2(3H)-one
      (MBF) and alpha-chloro-4-fluoroacetophenone (CFAP) in chemical process workers.

PMID- 8879939
TI  - Carbamazepine-induced drug rashes: diagnostic value of patch tests depends on
      clinico-pathologic presentation.

PMID- 8879940
TI  - Coexistence of contact urticaria and contact dermatitis due to pearl oysters in
      an atopic dermatitis patient.

PMID- 8879941
TI  - Opioid and opiate immunoregulatory processes.
AB  - The discovery of the ability of the nervous system to communicate through
      "public" circuits with other systems of the body is attributed to Ernst and Berta
      Scharrer, who described the neurosecretory process in 1928. Indeed, the immune
      system has been identified as another important neuroendocrine target tissue.
      Opioid peptides are involved in this communication (i.e., neuroimmune) and with
      that of autoimmunoregulation (communication between immunocytes). The
      significance of opioid neuropeptide involvement with the immune system is
      ascertained from the presence of novel delta, mu, and kappa receptors on
      inflammatory cells that result in modulation of cellular activity after
      activation, as well as the presence of specific enzymatic degradation and
      regulation processes. In contrast to the relatively uniform antinociceptive
      action of opiate and opioid signal molecules in neural tissues, the presence of
      naturally occurring morphine in plasma and a novel mu3, opiate-specific receptor
      on inflammatory cells adds to the growing knowledge that opioid and opiate signal
      molecules may have antagonistic actions in select tissues. In examining various
      disorders (e.g., human immunodeficiency virus, substance abuse, parasitism, and
      the diffuse inflammatory response associated with surgery) evidence has also been
      found for the involvement of opiate/opioid signaling in prominent mechanisms. In
      addition, the presence of similar mechanisms in man and organisms 500 million
      years divergent in evolution bespeaks the importance of this family of signal
      molecules. The present review provides an overview of recent advances in the
      field of opiate and opioid immunoregulatory processes and speculates as to their
      significance in diverse biological systems.

PMID- 8879942
TI  - Immunopathogenesis of virus diseases affecting the central nervous system.
AB  - A variety of viruses can cause diseases of the central nervous system by two
      different mechanisms. Cytolytic viruses exert direct effects on cells of the
      nervous system that result in death and cell loss. Noncytolytic viruses do not
      directly damage cells, but might harm cell functions in the long run. However,
      more common is the reaction of the immune system towards viral antigens of those
      noncytolytic viruses which ultimately might lead to an immunopathological
      disease. Several peculiarities of the central nervous system with regard to an
      immune reaction within this organ are discussed in the context of viral
      infections.

PMID- 8879943
TI  - Clinical decision-making in coronary artery disease.

PMID- 8879944
TI  - Endothelial dysfunction in coronary heart disease.
AB  - Atherosclerosis is a chronic disease characterized by the focal accumulation of
      plaque (leukocytes, macrophages, smooth muscle cells, lipids, and extracellular
      matrix) in the vessel wall that ultimately leads to obstruction of the lumen
      through gradual progression, plaque rupture with intraluminal thrombosis, or
      both. The "vulnerable" plaque is smaller in size, richer in lipids, and more
      infiltrated with macrophages than the stable fibromuscular lesion. Therefore,
      lowering the lipid or macrophage pools stored in the plaque may stabilize the
      plaque and reduce the risk for plaque rupture. Indeed, cholesterol-lowering
      trials have yielded a significant reduction in acute cardiac events.
      Antithrombotic therapy may further prevent acute coronary syndromes by altering
      the consequences of plaque rupture. However, we need to address the earlier
      stages of atherosclerosis, namely, endothelial dysfunction. Current hypotheses
      concerning its pathogenesis focus on vascular endothelial injury, the oxidation
      of low-density lipoprotein and its effects on the endothelium, which set off a
      cascade or responses involving the complex interaction of growth factors and
      cytokines leading to increased oxidative stress, increased free radical
      formation, destruction of nitric oxide, endothelial dysfunction, increased
      platelet aggregation, thrombosis, inflammation, plaque formation, proteolysis,
      plaque fissure, and rupture.

PMID- 8879945
TI  - Pathophysiology and initial management of the acute coronary syndromes.
AB  - Acute coronary syndromes are responsible for more than half a million hospital
      admissions each year in the United States alone. Plaque rupture is the
      precipitating pathophysiologic event. The degree of narrowing of plaques that
      rupture is not necessarily severe, in the range of 30% to 70% diameter stenosis.
      Plaques containing large lipid pools with only thin fibrous caps are most at
      risk. The site of rupture is most often at the shoulder of the plaque, where
      stress is highest. Clusters of macrophages are often seen at these points. Most
      plaque ruptures heal without causing symptoms, perhaps leaving a narrowing
      somewhat more severe than before. Plaque ruptures that expose larger areas of
      thrombogenic intramural debris to flowing blood in areas of high turbulence are
      most likely to provoke more extensive thrombosis. Risk factors, particularly
      smoking and hypercholesterolemia, cause increased thrombin deposition at the site
      of deep arterial injury. Thrombin deposition causes local coronary
      vasoconstriction that may contribute to the development of ischemia. Whether
      plaque rupture with thrombosis causes infarction, unstable angina, or no symptoms
      at all depends on the site of the lesion, its severity, and whether the
      jeopardized myocardium is served by collaterals. Aspirin, heparin, and,
      potentially, the newer agents provide benefit in each of the acute coronary
      syndromes.

PMID- 8879946
TI  - Gene therapy for ischemic heart disease.
AB  - Gene therapy techniques are being developed as potential treatments for
      dyslipidemias, coronary restenosis, and vein graft disease. Retroviral and now
      adenoviral gene delivery techniques are being studied. A human protocol for the
      treatment of familial hypercholesterolemia has recently been completed using ex
      vivo hepatic low-density lipoprotein receptor gene transfer via a retroviral
      vector. Work in most other areas is currently in the animal model stage.
      Significant progress has been made in the area of coronary restenosis,
      particularly in identifying target genes to reduce neointima formation, such as
      herpesvirus thymidine kinase and the retinoblastoma gene. Work also continues in
      developing strategies to decrease neointima formation in vein grafts used in
      coronary bypass surgery and in improving methods of myocardial protection during
      surgery.

PMID- 8879947
TI  - Determinants of infarct size in acute myocardial infarction in patients treated
      with reperfusion therapy.
AB  - Infarct size after reperfusion therapy is determined by the extent of myocardium
      at risk, the degree of residual blood flow within the jeopardized zone, and the
      duration of coronary occlusion. This review article will explore the noninvasive
      methods that have been used to measure these variables. Recent advances in
      nuclear cardiology techniques will be discussed in detail, because new agents
      have the ability to accurately quantify these variables.

PMID- 8879948
TI  - Quantitative echocardiography in left ventricular remodeling after myocardial
      infarction.
AB  - Two-dimensional transthoracic echocardiography has been used to study patients
      during and after myocardial infarction. Quantitative studies have revealed that
      progressive increase in left ventricular size is associated with a poor
      prognosis. When pre-defined echocardiographic criteria were used to stratify
      infarction patients for adverse cardiovascular outcome, the efficacy of combined
      thrombolysis and angiotensin-converting enzyme inhibitor therapy could be shown
      in those who developed left ventricular enlargement. Other descriptors of left
      ventricular architecture and function, such as cavity shape and the ratio of
      short-axis left ventricular muscle to cavity area, may predict cardiovascular
      death and severe heart failure.

PMID- 8879949
TI  - The role of cardiac imaging and biochemical markers in patients with acute chest
      pain.
AB  - Acute chest pain syndromes are common, with over 6 million patients in the United
      States presenting to emergency departments with suggestive symptoms. This review
      concentrates on the previous models and new diagnostic testing procedures. The
      different modalities emphasized are computer-generated models, serum markers,
      echocardiography, and nuclear imaging in the emergency department. The use of new
      markers and imaging may help to risk-stratify patients earlier for potential
      treatment and triage decisions.

PMID- 8879950
TI  - Myocardial viability in patients with coronary artery disease and left
      ventricular dysfunction: transplantation or revascularization?
AB  - Coronary artery bypass surgery performed in patients with coronary artery disease
      and left ventricular dysfunction improves survival compared with antianginal
      therapy alone. The mechanisms for this survival advantage with revascularization
      therapy have not been systematically elucidated. Many of these patients have
      "hibernating" myocardium secondary to chronic ischemia with the potential for
      substantial improvement in left ventricular function and heart failure symptoms
      following revascularization therapy. Nevertheless, as survival with cardiac
      transplantation continues to improve, a significantly larger number of patients
      with coronary artery disease and left ventricular dysfunction are being referred
      for cardiac transplantation in lieu of revascularization surgery. Recently
      developed imaging modalities, which include positron emission tomography,
      thallium imaging, and dobutamine echocardiography, can reliably predict recovery
      of regional myocardial dysfunction after revascularization in these areas of
      hibernating heart. New modalities to detect hibernating myocardium include 99mTc
      sestamibi, contrast echocardiography, nuclear magnetic resonance spectroscopic
      imaging, and ultrasonic tissue characterization. In an era of medicine
      characterized by increased concern for cost containment and the judicious
      application of expensive technology, the choice of the most appropriate tests to
      detect viability is a growing challenge and is essential in the choice between
      transplantation and revascularization.

PMID- 8879951
TI  - Two-dimensional stress echocardiography in coronary artery disease.
AB  - Stress echocardiography done using various methods has become a primary way to
      assess and quantify the extent of myocardial ischemia. Although it is highly
      versatile, its use remains patchy, and in many centers it is simply considered a
      research technique. This review discusses some of the advantages of stress
      echocardiography in relation to recent publications, and it points to some areas
      for future research.

PMID- 8879952
TI  - The role of noninvasive testing in evaluating patients for coronary artery
      disease.
AB  - Risk stratification of patients with coronary artery disease using noninvasive
      imaging techniques has become increasingly more important in the cost-conscious
      delivery of patient care. This is evidenced by significant developments involving
      both nuclear cardiology and echocardiography for the assessment of viability,
      silent myocardial ischemia and prognosis, as well as the emergence of new
      techniques, in particular the use of positron emission tomography isotopes with
      single photon emission computed tomography cameras and low-dose dobutamine
      echocardiography in the detection of viability. New developments regarding
      screening for and the clinical importance of silent myocardial ischemia as well
      as new developments regarding classification of radionuclide perfusion defects
      and stress echocardiograms that portend a poor prognosis are also reviewed.
      Finally, new techniques and stress agents have been development that add to the
      choices available to the clinician for the optimal assessment of the patient
      being considered for revascularization.

PMID- 8879953
TI  - Lipid-lowering therapy for patients with or at risk of coronary artery disease.
AB  - Several studies have shown that effective lipid-lowering therapy slows the
      progression of atherosclerotic lesions in the coronary and carotid arteries.
      Recent clinical trials have confirmed and extended previous work showing that
      lowering cholesterol reduces the risk of coronary events. A clear reduction in
      major coronary events during treatment for 5 years with the hydroxymethylglutaryl
      coenzyme A reductase inhibitor pravastatin was observed in the West of Scotland
      study and in the preliminary results of the Cholesterol and Recurrent Events
      study. The Scandinavian Simvastatin Survival Study has provided the first
      unequivocal demonstration of improved survival as a result of lipid-lowering
      therapy. These three trials, which together included over 15,000 patients studied
      for 5 years, have provided good evidence that noncardiovascular mortality is not
      affected by substantial reductions in blood cholesterol.

PMID- 8879954
TI  - Risk stratification after myocardial infarction in the thrombolytic era.
AB  - Most patients with acute myocardial infarction do not receive or are ineligible
      for thrombolytic therapy, and thus their prognosis is worse than that of the
      populations studied in the major, randomized, lytic therapy trials. We need to
      devise a cost-effective strategy with which to appropriately stratify these
      patients. Simple, easily ascertained clinical variables that are evident soon
      after hospital admission can identify higher-risk patients, who are likely to be
      older and less able to adequately complete an exercise test. In some patients,
      nuclear imaging tests are appropriate; low-dose dobutamine echocardiography and
      ambulatory ECG monitoring may also have a role. Greater use of routine cardiac
      catheterization (with assessment of ventricular function) might be the most
      appropriate way to stratify patients because it may overcome some of the
      limitations of noninvasive testing, will clearly define high-risk patients, and
      may facilitate early discharge from the hospital. Left ventricular function and
      the patency of the infarct-related artery will be determined, and patients with
      left main coronary disease, significant three-vessel coronary artery disease, and
      two-vessel coronary disease (especially with proximal left anterior descending
      coronary artery involvement) will be identified. An aggressive strategy of
      revascularization to improve survival in appropriate patients may be employed.
      Greater use of routine coronary arteriography after acute myocardial infarction
      would inevitably lower the threshold for inappropriate, potentially risky, and
      expensive further interventions. We need to focus our attention on the most
      appropriate strategies for the management of patients whose prognosis is worse
      than the prognosis of those who receive lytic therapy after acute myocardial
      infarction.

PMID- 8879955
TI  - Calcium-channel blockers in ischemic heart disease.
AB  - Recent reports add to a growing body of evidence that short-acting calcium
      channel blockers, whether used for hypertension, unstable angina, or acute
      myocardial infarction, may have unfavorable effects. Short-acting nifedipine has
      no role in acute myocardial infarction, and the United States Food and Drug
      Administration has recently issued a warning discouraging its use in hypertension
      and unstable angina. Other short-acting calcium antagonists such as diltiazem and
      verapamil may have associated adverse effects as well, although the evidence is
      not as definitive. What effect sustained-release preparations and newer calcium
      antagonists have on the clinical endpoints of myocardial infarction and death is
      not known, and large prospective randomized clinical trials with these
      medications, some of which are underway, are needed to address these issues.
      Until that time, only medications with clearly documented efficacy and safety
      should be used for first-line therapy for hypertension, unstable angina, and
      acute myocardial infarction.

PMID- 8879956
TI  - Postmenopausal hormones and coronary heart disease.
AB  - Women who self-select to take postmenopausal hormones have lower risks of
      coronary heart disease, their leading cause of mortality. Women and their primary
      health care providers must weigh this and other clear (osteoporosis), and
      possible (stroke, colon cancer, and Alzheimer's disease) benefits against clear
      (endometrial cancer) and possible (breast cancer) risks. Because all existing
      data derive only from observational studies, reliable information on the balance
      of risks and benefits must await the results of the Women's Health Initiative, a
      large-scale, randomized clinical trial.

PMID- 8879957
TI  - Evaluation of coronary artery disease in women.
AB  - Diagnostic techniques have been refined to improve the accuracy of coronary
      artery disease detection in women compared to that achieved by clinical
      assessment and stress electrocardiography alone. Noninvasive cardiac imaging with
      99mTc myocardial perfusion agents improves the specificity of coronary artery
      disease diagnosis over that achieved with 201Tl imaging, particularly when this
      technique is combined with ECG-gated image analysis. Improvements in diagnostic
      accuracy should enhance physician confidence in the use of noninvasive diagnostic
      testing in women. Combined clinical and noninvase imaging assessment can define
      those women at very high and very low risk for future cardiac events, permitting
      physicians to direct appropriate patients to aggressive treatment (ie, coronary
      revascularization) to improve outcomes. The reduction in unneccessary coronary
      cardiac catheterization accomplished by improved specificity, and the accurate
      determination of cardiac risk, provides for the most cost-efficient use of
      medical resources in the female population with known or suspected coronary
      artery disease.

PMID- 8879958
TI  - Ischemic heart disease.

PMID- 8879959
TI  - Modern management of acute myocardial infarction.

PMID- 8879960
TI  - Absence of the Gly40-ser mutation in the glucagon receptor gene in Japanese
      subjects with NIDDM.
AB  - Recent studies have shown both association and linkage between a Gly40-Ser
      mutation in the glucagon receptor gene and NIDDM in French patients with familial
      NIDDM. This mutation was present in heterozygous form in 4.6% of diabetic
      probands but only 1% of the French population, suggesting that it was an
      important risk factor in the development of NIDDM. A total of 348 unrelated
      Japanese subjects (220 with NIDDM, 53 with impaired glucose tolerance (IGT) and
      75 normal subjects) were screened for the presence of the Gly40-Ser mutation.
      Seventy-two percent of the NIDDM patients and 52% of IGT subjects had a positive
      family history of NIDDM. The Gly40-Ser mutation, which could be readily detected
      in a positive control subject, was not found in any of the 348 Japanese subjects
      studied. Thus, the Gly40-Ser mutation does not play an important role in the
      pathogenesis of NIDDM in Japanese patients.

PMID- 8879961
TI  - Influence of glycemic control on viscosity and density of plasma and whole blood
      in type-1 diabetic patients.
AB  - The hemorheological properties of blood play an important role in determining
      blood flow. Blood inertia, as characterized by blood density, controls blood flow
      in the large arteries, whereas blood viscosity becomes increasingly important
      with decreasing vessel diameter. In order to evaluate the impact of glycemic
      control on the rheological properties of blood, we examined viscosity (shear
      range: 600-0.2 s-1) and density of plasma and whole blood in 26 Type-1 diabetic
      patients and in 24 healthy controls, matched for age and sex. The diabetic
      subjects were subdivided into two groups according to their degree of glycemic
      control: 14 patients with good (HbA1c = 7.1 +/- 0.6%), and 12 patients with poor
      control (HbA1c = 8.7 +/- 0.7%). Diabetic patients as a whole did not differ from
      healthy controls in any of the rheological parameters. Subdivision of the
      patients due to their degree of glycemic control led to a marked rheological
      separation of Type-1 diabetic subjects with significantly lower plasma (P <
      0.008) and whole blood viscosity (P < 0.03 at 10 and 25 s-1), and plasma density
      (P < 0.05) in well controlled patients. Compared with healthy controls, well
      controlled diabetic patients had significantly lower values of viscosity (P <
      0.005) and density (P < 0.05) of plasma. Poorly controlled patients, on the other
      hand, did not differ from healthy controls in the examined rheological
      parameters. There seems to be a positive influence of good glycemic control on
      hemorheology in Type-1 diabetic patients.

PMID- 8879962
TI  - The effect of metformin on liver blood flow in vivo in normal subjects and
      patients with non insulin dependent diabetes.
AB  - We previously reported that metformin improves insulin-mediated glucose liver
      metabolism in patients with non insulin dependent diabetes (NIDDM). It is not
      clear whether this is a direct effect of metformin on liver metabolism or
      mediated by other mechanisms such as increased liver blood flow. In this respect
      it has recently been reported that metformin increases hepatic blood flow (HBF)
      in diabetic rats. The aim of this study was to evaluate whether the
      administration of metformin is associated with modifications in HBF in humans.
      Patients affected by NIDDM (n = 11) and normal subjects (n = 6) were studied. In
      the first protocol HBF was investigated in six overweight (BMI 27 +/- 2 Kg/m2)
      NIDDM patients and six normal subjects (age and BMI matched) already on metformin
      treatment before and 2 h after the administration of 500 mg metformin. In the
      second protocol HBF was investigated in obese (BMI 32 +/- 1 Kg/m2) NIDDM patients
      (n = 5) in good metabolic control before and after 15 days of metformin at the
      dose of 1 g daily. HBF was measured by intravenous injection of 3 mCi 99mTc
      phytate. In both protocols no significant changes in HBF were observed following
      metformin administration either in NIDDM patients or normal subjects. No
      significant differences were observed in HBF between diabetic patients and normal
      subjects. These data indicate that metformin has no effect on HBF in man. The
      previously reported improvement of insulin mediated liver metabolism induced by
      metformin is likely to be a consequence of the direct effect of the drug at
      hepatocyte level which is independent of HBF modifications.

PMID- 8879963
TI  - Islet cell antibodies and antibodies against glutamic acid decarboxylase in newly
      diagnosed adult-onset diabetes mellitus.
AB  - This study aimed to determine the prevalence of antibodies against glutamic acid
      decarboxylase (anti-GAD) and islet cell antibodies (ICA) in relation to beta-cell
      function in adults newly-diagnosed with diabetes mellitus. beta-cell function was
      assessed in adults aged 25-70 years newly-diagnosed with diabetes mellitus (n =
      84) and control subjects (n = 34) using a 1.6 MJ mixed meal test procedure. beta
      cell function was evaluated by the true insulin (defined as immunoreactive
      insulin minus proinsulin) response to the mixed meal test. Subjects were
      classified on the basis of the area under the true insulin curve (normal 16830
      107700 pmol min/I) and the sum of the 30 and 60 min incremental response (normal
      285-3295 pmol/I). The prevalence of anti-GAD and ICA was determined using
      radioimmunoprecipitation and indirect immunofluorescence, respectively. Twelve
      (14%) of the study cohort were insulin deficient showing little or no true
      insulin release. Of the insulin deficient individuals, seven (58%) subjects were
      anti-GAD antibody positive, compared with eleven (15%) of the subjects without
      insulin deficiency (P < 0.001). Seven (58%) insulin deficient subjects were ICA
      positive, whereas only two (3%) non-insulin deficient subjects were ICA positive
      (P < 0.001). Eight (67%) of the insulin deficient individuals had anti-GAD or
      ICA, compared with twelve (17%) of those who were not insulin deficient (P <
      0.001). The positive predictive values for insulin deficiency of anti-GAD and ICA
      were 39 and 78% respectively. The sensitivity of both antibodies for detecting
      insulin deficiency was 50%. The specificity for detecting insulin deficiency was
      85% for anti-GAD and 97% for ICA. Positivity for both anti-GAD and ICA gave a
      specificity and positive predictive value for insulin deficiency of 99%, and a
      sensitivity of 50%. Nearly one in seven adults presenting with diabetes mellitus
      as a new diagnosis are insulin deficient using our criteria. Loss of beta-cell
      function in two thirds of individuals who are insulin deficient can be identified
      by anti-GAD and ICA. Early detection of these immune markers of beta-cell damage
      creates the potential for immune modulation to limit such damage.

PMID- 8879964
TI  - Clinical significance of measurements of urinary and serum thrombomodulins in
      patients with non-insulin-dependent diabetes mellitus.
AB  - The aim of our study was to elucidate whether serum thrombomodulin (S-TM) and
      urinary thrombomodulin (U-TM) levels would reflect the pathogenesis of diabetic
      complications. Studies were conducted in 188 patients with non-insulin-dependent
      diabetes mellitus (NIDDM) and 132 age-matched healthy subjects. TM was measured
      by a newly developed enzyme immunoassay. Both S-TM and U-TM levels in NIDDM were
      much higher than those in healthy controls. S-TM values in NIDDM correlated
      significantly with age (P < 0.05), HbA1c (P < 0.05), serum 1.5 anhydroglucetol
      (AG) (P < 0.05) and urinary albumin concentration (UAC) (P < 0.01), respectively.
      On the other hand, fasting plasma glucose (FPG) (P < 0.001), HbA1c (P < 0 .01),
      serum fructosamine (P < 0.05) and serum 1.5 AG (P < 0.05) were closely correlated
      with U-TM values in NIDDM. Patients with clinical nephropathy showed obviously
      higher S-TM levels (P < 0.05) than patients with latent nephropathy. Furthermore,
      S-TM values in patients with diabetic proliferative retinopathy increased
      significantly compared with those in patients without diabetic retinopathy (P <
      0.05). When all diabetic patients with normoalbuminuria were studied, no
      significant changes of S-TM were observed between the no diabetic retinopathy
      group and the proliferative diabetic retinopathy group. CONCLUSIONS: The present
      data suggest that an increase in U-TM reflects the grade of glucose metabolism,
      whereas an increase in S-TM appears to reveal the advance of diabetic
      microangiopathy, including nephropathy.

PMID- 8879965
TI  - Lipoprotein(a) concentrations and non-insulin-dependent diabetes mellitus:
      relationship to glycaemic control and diabetic complications.
AB  - The aim of our study was to determine the lipoprotein(a) (Lp(a)) levels in
      patients with non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate
      Lp(a) concentrations in relation to glycaemic control and diabetic complications.
      We evaluate in a cross-sectional study a total of 103 NIDDM patients (52 males
      and 51 females; mean age of 62.5 years; mean of diabetes duration: 12 years)
      referred to our hospital because of poor glycaemic control, and a group of 108
      non-diabetic subjects (57 males and 51 females). RESULTS: mean Lp(a)
      concentration did not significantly differ between NIDDM patients and non
      diabetic subjects (11.1 +/- 14 vs. 16.2 +/- 14 mg/dl). The distribution of Lp(a)
      levels was highly skewed towards the lower levels in both groups, being over 30
      mg/dl in only 6% of NIDDM patients and 12% of controls. Patients with Lp(a)
      levels over 10 mg/dl had lower haemoglobin Alc (HbA1c) than patients with Lp(a)
      levels over 10 mg/dl (8.5% vs. 10.4%; P < 0.01). Lp(a) concentration was
      positively correlated with body mass index (BMI) (P < 0.05) and HbA1c (P < 0.05).
      No association was found between Lp(a) and sex, age, other lipidic parameters,
      microalbuminuria, type of treatment and presence of cardiovascular disease. These
      findings may suggest that glycaemic control could have a modulatory role on Lp(a)
      concentration in NIDDM patients. In this study, diabetic complications did not
      seem to be associated with higher Lp(a) concentrations.

PMID- 8879966
TI  - Relationship between plasminogen activator inhibitor type-1 plasma levels and the
      lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus.
AB  - The first part of the paper deals with the relationship between two inhibiting
      factors of the complex enzyme cascade regulating fibrinolysis, namely plasminogen
      activator inhibitor type-1 (PAI-1) and lipoprotein(a) (Lp(a)). Blood
      concentrations of Lp(a), PAI-1 antigen (PAI-1 AG) and activity (PAI-1 AT), and
      the main parameters of lipo- and glyco-metabolic balance were studied in 80 type
      II diabetic patients. Roughly hyperbolic patterns have been found between PAI-1
      and Lp(a). Negative statistically significant linear correlation can be elicited
      when Log PAI-1 AG and Log PAI-1 AT values are plotted versus Lp(a) values, the
      first one being particularly tight. These findings suggest a nearly on/off
      control of the two parameters, limiting the risk of hypofibrinolysis. The second
      part of the paper was aimed at verifying this hypothesis. A group of 30 diabetic
      patients were treated for 3 months with metformin, an antidiabetic biguanide
      compound which has been reported to reduce PAI-1 levels both in diabetic and in
      non-diabetic patients. Metformin significantly reduced PAI-1 AG and PAI-1 AT but
      did not influence plasma Lp(a) levels. A clear linear correlation between the
      basal Lp(a) values and the changes in PAI-1 AG levels was found. An even tighter
      correlation was elicited between the decrease in PAI-1, and PAI-1 pretreatment
      values.

PMID- 8879967
TI  - Reduced hydrogen peroxide production in neutrophils from patients with diabetes.
AB  - We evaluated the effects of granulocyte colony-stimulating factors (G-CSF),
      granulocyte-macrophage colony-stimulating factors (GM-CSF) and phorbol myristate
      acetate (PMA) on H2O2 production in purified neutrophils from patients with
      diabetes mellitus (DM), using flow cytometry. Twenty-two age-matched male
      subjects were selected: 11 were normal volunteers and the remainder had DM. No
      significant differences in intracellular H2O2 production per 60 min was observed
      in the "resting' neutrophils from DM patients (37.2 +/- 20.4 A.U.) compared with
      those from normal volunteers (24.9 +/- 8.4 A.U.). The PMA-stimulated neutrophils
      from normal volunteers generated approximately 4-fold increases in H2O2 per 60
      min compared with those from DM patients. Under similar culture conditions, G-CSF
      caused 1.6-fold increases of H2O2 in neutrophils from normal volunteers compared
      with those of DM patients. Increases after GM-CSF stimulation were 2-fold higher
      in volunteer neutrophils compared with those from DM patients. The levels of G
      CSF- or GM-CSF-stimulated H2O2 production in neutrophils from DM patients were
      low and were little different from non-stimulated resting cells. These data
      showed that H2O2 production in neutrophils induced by PMA is impaired in patients
      with DM, and neither G-CSF nor GM-CSF enhances its production.

PMID- 8879968
TI  - Patient administrative system as a tool to validate the ascertainment in the
      diabetes incidence study in Sweden (DISS).
AB  - The aim of this study was to evaluate the degree of ascertainment in a nationwide
      prospective registration of incident cases of diabetes mellitus in the age group
      15-34 years (The Diabetes Incidence Study in Sweden (DISS)). Incident cases of
      diabetes mellitus in DISS during a five year period were compared with
      inpatients, with the diagnosis of diabetes mellitus, registered in a routine
      computer-based administrative register. The Patient Administrative System
      Inpatient Care (PAS-IC). To clarify this issue the two-sample capture-recapture
      phenomena was employed in the two southernmost counties in Sweden, Malmohus and
      Kristianstad, covering 9.2% of the total of 2.3 million people aged 15-34 years
      in Sweden. The results showed that the ascertainment level in DISS was 0.86 for
      insulin dependent diabetes mellitus (IDDM). Hence, the DISS registry is a valid
      tool to monitor the incidence of IDDM in young (15-34 years) adult subjects.

PMID- 8879969
TI  - Coenzyme Q10 and insulin secretion in vitro.

PMID- 8879970
TI  - Anticonvulsant-induced psychiatric disorders. The role of forced normalisation.
AB  - With the introduction of several new anticonvulsant drugs into clinical practice
      in recent years, renewed attention has been paid to treatment-emergent effects,
      especially behavioural syndromes. In this review, the more severe psychiatric
      syndromes that may be associated with anticonvulsants are discussed, especially
      personality disorders, affective syndromes and psychoses. The important concept
      of forced normalisation is discussed, and its clinical counterpart, alternative
      psychosis. Affective disorders and psychoses have been described as associated
      with most of the new anticonvulsant agents, and they are often seen in a setting
      in which previously intractable patients suddenly become seizure free. Other
      cases may relate to intoxication, the precipitation of a status epilepticus, or
      ensue as part of the background frequency of those syndromes that are seen in
      epilepsy irrespective of medication.

PMID- 8879971
TI  - Cisapride. Drug interactions of clinical significance.
AB  - Cisapride is a prokinetic agent which restores motility of the gastrointestinal
      tract in conditions of decreased bowel transit. It may also alter the absorption
      of coadministered drugs. The absorption of morphine, diazepam, cyclosporin,
      alcohol (ethanol) and levodopa are increased. Initial absorption of cimetidine
      and raniditine is also increased, but overall absorption is lower due to
      increased bowel transit. The absorption of digoxin, propranolol and the
      anticoagulants warfarin and phenprocoumon appears unaffected by cisapride,
      although increase thrombotest values were seen with acenocoumarol (nicoumalone).
      Drug interactions leading to increased plasma concentrations of cisapride may
      produce an increase in adverse effects. The most important of these is QT
      interval prolongation and ventricular arrhythmias. Phenytoin does not appear to
      affect protein binding of cisapride. Cisapride metabolism is inhibited by the
      antifungals ketoconazole, fluconazole, itraconazole and miconazole, and by the
      antibacterials erythromycin, troleandomycin and clarithromycin. Cisapride should
      not be coadministered with these drugs. Cimetidine produces a small increase in
      cisapride plasma concentrations, which may be due to inhibition of metabolism.
      Cisapride absorption is unaffected by other antacids. Atropine may reverse the
      cisapride-induced increase in peristalsis. Prescribers should remain vigilant to
      the presence of these and other, as yet unreported, reactions.

PMID- 8879972
TI  - Treatment of HIV infection. Tolerability of commonly used antiretroviral agents.
AB  - There are a number of agents available that are active against HIV. Eight drugs
      are already licensed in the US: the nucleoside analogue reverse transcriptase
      inhibitors--zidovudine, didanosine, zalcitabine, stavudine and lamivudine--and
      the HIV protease inhibitors--saquinavir, indinavir and ritonavir. Antiretroviral
      drugs have been given as monotherapy, often as sequential monotherapy, and in
      alternating or simultaneous combinations. Since combination therapy has recently
      been shown to be superior to monotherapy, antiretrovirals will increasingly be
      given in combination. All available antiretroviral drugs show considerable
      toxicity complicating their use. In this article we describe the adverse effects
      of the above mentioned nucleoside analogues used in monotherapy and of several
      combinations of antiretroviral drugs. No unexpected toxicities were found in
      several different combinations tested to date and, for most combinations, no
      synergistic toxic effects have been reported.

PMID- 8879973
TI  - Role of magnesium sulfate in seizure prevention in patients with eclampsia and
      pre-eclampsia.
AB  - Eclampsia is a leading cause of maternal mortality. The prevention of seizure
      activity in pre-eclampsia and recurrent seizures in eclamptic patients is an
      essential aspect of management. Many drugs with anticonvulsant properties have
      been used to treat patients with pre-eclampsia and eclampsia. Magnesium sulfate
      is a significantly better drug than either diazepam or phenytoin for preventing
      recurrent seizures in eclamptic patients. Magnesium sulfate has diverse
      cardiovascular and neurological effects and also alters calcium metabolism.
      Although the drug crosses the placenta and may affect the fetus, these effects
      are clinically small and fetal morbidity has been shown to be reduced in
      randomised studies comparing magnesium sulfate to either phenytoin or
      benzodiazepines. Dosage regimens of magnesium sulfate are empirical. Because
      adverse effects of this agent are related to toxicity, the establishment of
      greater efficacy by using higher dosage regimens needs to be tested against a
      greater risk of adverse effects. The most serious toxicity related to magnesium
      sulfate use is magnesium sulfate use is neuromuscular blockade that may result in
      respiratory arrest. Magnesium sulfate is now the drug choice for treating
      eclamptic patients. However, further studies are required to establish the role
      of this agent as a prophylactic agent in the prevention of eclampsia.

PMID- 8879974
TI  - ACE inhibitors and the kidney. A risk-benefit assessment.
AB  - ACE inhibitors effectively reduce systemic vascular resistance in patients with
      hypertension, heart failure or chronic renal disease. This antihypertensive
      efficacy probably accounts for an important part of their long term
      renoprotective effects in patients with diabetic and non-diabetic renal disease.
      The renal mechanisms underlying the renal adverse effects of ACE inhibitors-
      intrarenal efferent vasodilation with a consequent fall in filtration pressure-
      are held to be involved in their renoprotective effects as well. The fall in
      filtration pressure presumably contributes to the antiproteinuric effect as well
      as to long term renoprotection. The former is suggested by the positive
      correlation between the fall in filtration fraction and the reduction in
      proteinuria found during ACE inhibition. The latter is suggested by the
      correlation between the (slight) reduction in glomerular filtration rate at onset
      of therapy and a more favourable course of renal function in the long term. Such
      a fall in filtration rate at the onset of ACE inhibitor treatment is reversible
      after withdrawal, and can be considered the trade-off for long term renal
      protection in patients with diabetic and nondiabetic chronic renal disease. In
      conditions in which glomerular filtration is critically dependent on angiotensin
      II-mediated efferent vascular tone (such as a post-stenotic kidney, or patients
      with heart failure and severe depletion of circulating volume), ACE inhibition
      can induce acute renal failure, which is reversible after withdrawal of the drug.
      Systemic and renal haemodynamic effects of ACE inhibition, both beneficial and
      adverse, are potentiated by sodium depletion. Consequently, sodium repletion
      contributes to the restoration of renal function in patients with ACE inhibitor
      induced acute renal failure. Our the other hand, co-treatment with diuretics and
      sodium restriction can improve therapeutic efficacy in patients in whom the
      therapeutic response of blood pressure or proteinuria is insufficient. Patients
      at the greatest risk for renal adverse effects (those with heart failure,
      diabetes mellitus and/or chronic renal failure) also can expect the greatest
      benefit. Therefore, ACE inhibitors should not be withheld in these patients, but
      dosages should be carefully titrated, with monitoring of renal function and serum
      potassium levels.

PMID- 8879975
TI  - Depot medroxyprogesterone acetate and breast cancer. A review of current
      knowledge.
AB  - Depot medroxyprogesterone acetate (DMPA) has been used worldwide since 1964 as a
      contraceptive and by 1993 was in use in more than 90 countries. It was licensed
      for contraceptive use in the US in 1992. One of the reasons for this delay in
      licensing in the US was the possibility of an increased risk of breast cancer
      associated with its use. A pooled analysis has recently been published, which
      brings together the data from 2 large studies of breast cancer risk associated
      with DMPA use. The overall results are reassuring, but there is some evidence of
      an increased risk of breast cancer associated with recent use of DMPA. There are
      substantial difficulties in interpreting this increase in risk. It is certainly
      possible that it may be the result of surveillance bias, although it could be a
      short term increase in risk that is not in fact sustained. The conclusion that
      DMPA should not be restricted as a contraceptive, provided that appropriate
      advice is given before use, is well-founded. However, further epidemiological
      work is needed on the long term effects of DMPA.

PMID- 8879977
TI  - Growth inhibition of K-ras-expressing tumours by a new vinca alkaloid,
      conophylline, in nude mice.
AB  - Conophylline, a new vinca alkaloid isolated from the plant Ervatamia microphylla
      induced normal flat morphology in K-ras-NRK and K-ras-NIH cell lines, and lowered
      the increased uptake of 2-deoxyglucose in K-ras-NRK cells. Conophylline inhibited
      the growth of K-ras-NRK cells, but this inhibition was reversible. The alkaloid
      also inhibited the growth of K-ras-NRK and K-ras-NIH3T3 tumours transplanted into
      nude mice. On the other hand, it showed no effect on survival of the mice loaded
      with L1210 leukaemia. Thus, conophylline is a new antitumour vinca alkaloid that
      induced normal phenotypes in ras-expressing cells.

PMID- 8879978
TI  - The cellular toxicity of two antitumoural agents derived from platinum,
      cisplatinum versus oxaliplatinum, on cultures of tubular proximal cells.
AB  - There is a large scope for the use for cisplatin and its derivatives in the
      treatment of human malignancies. Nephrotoxicity is their most important use
      limiting factor. The aim of this study has been to compare cisplatin (CDDP) and
      oxaliplatin (1-OHP), a new derivative, on cultures of tubular proximal cells.
      Three cells models were used: primary culture of rabbit kidney, proximal tubular
      cells (RPTC) and established opossum kidney (OK) and pig kidney (LLC-PK1)
      epithelial cell lines. Results indicate that in these three culture systems, the
      cytotoxicity-ranking of the two molecules were in agreement with their in vivo
      nephrotoxicity (CDDP > 1-OHP), but were less cytotoxic for OK and LLC-PK1 cells
      than for RPTC. Functional and biochemical evaluations in RPTC indicate that toxic
      effects of platinum derivates are exerted on DNA, protein synthesis and glucose
      uptake. 1-OHP effect on DNA synthesis seems to be more effective, but induced a
      more progressive cytotoxicity. Alteration of glutathione-dependent detoxication
      activities may reflect the occurrence of a lipid peroxidation process. The
      present study showed that 1) RPTC are more suitable that LLC-PK1 or OK cells for
      investigating the nephrotoxicity of platinum derivatives; 2) 1-OHP seems to have
      a more powerful pharmacological effect than CDDP. The toxic effect ratio seems to
      promise greater safety with 1-OHP than with CDDP.

PMID- 8879979
TI  - Does the appearance of drug resistance during therapy alter bacterial
      susceptibility to opsonophagocytosis?
AB  - Coagulase-negative staphylococci (CNS) are common causes of infection in patients
      undergoing chronic ambulatory peritoneal dialysis (CAPD). Their ability to
      survive intracellularly within peritoneal macrophages and to persist within the
      peritoneum during antibiotic therapy has led to the development of drug
      resistance during treatment. Strains of Staphylococcus epidermidis (SE) and
      Staphytococcus haemolyticus (SH) have been isolated from patients with CAPD
      during treatment with ciprofloxacin. The respective MIC values pre-and post
      therapy were SE-0.25 and 128 mg/L and SH-0.50 and 64 mg/L. The susceptibility of
      each isolate to opsonophagocytosis was measured in vitro using isolated
      polymorphonuclear leucocytes (PMN) derived from fresh human blood donations. The
      bacteria were radiolabelled during growth, opsonised in either 1 or 10% serum and
      their uptake measured No differences were seen between the pre- and post therapy
      isolates when using 10% serum as opsonic source (18 vs. 21%); with 1% serum the
      corresponding values were lower (5 and 8% respectively). Similarly their ability
      to generate a respiratory burst as measured by chemiluminescence (CL) in the
      phagocytic cells was not diminished in the strains which had developed resistance
      to ciprofloxacin. The mean CL response to the strains isolated at outset of
      therapy ranged from 0.35-0.45 cpsc, and to the resistant strains following
      therapy from 0.36-0.50 cpsc. It is clear from the present investigation that
      although the bacterial strain became at least 10 times more resistant to
      ciprofloxacin during therapy, no change in their susceptibility to phagocytosis
      occurred refuting the idea that the emergence of drug resistant strains during
      therapy results in "super-bugs" of greater virulence.

PMID- 8879980
TI  - A relationship between serum gentamicin concentrations and minimal inhibitory
      concentration.
AB  - Since there are few widely accepted guidelines upon which to base therapeutic
      decisions and adjust for the many variables which may influence the ultimate
      therapeutic outcome, and few studies have evaluated what the optimal peak
      concentration-to-MIC ratio should be, pharmacokinetic parameters were estimated
      from pre- and post-dose concentrations measured in 30 orthopaedic patients,
      receiving gentamicin. The fluorescence polarization method was used, and
      simultaneous determination of the MIC (minimal inhibitory concentration) has been
      made. When Gram(-) microorganisms were incriminated for the infection, the
      optimal peak concentration exceeded the MIC by more than 3-fold in our serum
      samples. In Gram(+) bacteria, the peak antibacterial activity usually obtained
      tended to be lower (between 1.5 and 2). No correlation was found for the nadir
      bacteriostatic level. Our investigations showed that the peak bacteriostatic
      activity correlated well with response to therapy. Based on these findings, the
      peak antibacterial activity should therefore be between 1.5 and 2 for Gram(+) and
      greater than 3-fold for Gram(-) microorganisms, and these values seem to be
      effective for eradication of the infection.

PMID- 8879976
TI  - Gingival enlargement induced by drugs.
AB  - Gingival enlargement, an abnormal growth of the periodontal tissue, is mainly
      associated with dental plaque-related inflammation and drug therapy. Its true
      incidence in the general population is unknown. Gingival enlargement produces
      aesthetic changes, pain, gingival bleeding and periodontal disorders. Although
      gingival overgrowth has been traditionally recognised as an adverse effect of
      phenytoin therapy, it has recently been reported in association with the use of
      cyclosporin and calcium antagonists. These 3 classes of drugs produce important
      changes in fibroblast function, which induce an increase in the extracellular
      matrix of the gingival connective tissue. In the majority of those patients for
      whom dosage reduction, or drug discontinuation or substitution is not possible,
      and for whom prophylactic measures have failed, surgical excision of gingival
      tissue remains the only treatment of choice.

PMID- 8879982
TI  - Efficacy and safety of the standardised Ginseng extract G115 for potentiating
      vaccination against the influenza syndrome and protection against the common cold
      [corrected].
AB  - The aim of the study was to determine the properties of a standardized extract of
      ginseng root in inducing a higher immune response in vaccination against
      influenza. Attention was also paid to the common cold in this multicentre, two
      arm, randomized, placebo-controlled, double-blind investigation. A total of 227
      volunteers who visited 3 private practices in Milan received daily oral capsule
      doses of either placebo (113) or 100 mg of standardized ginseng extract Ginsana G
      115 (114) for a period of 12 weeks within which they received an anti-influenza
      polyvalent vaccination at week 4. As a result, while the frequency of influenza
      or common cold between weeks 4 and 12 was 42 cases in the placebo group, it was
      only 15 cases in the G115 group, the difference being statistically highly
      significant (p < 0.001). Whereas antibody titres by week 8 rose to an average of
      171 units in the placebo group, they rose to an average of 272 units in the G115
      group (p < 0.0001). Natural killer (NK) activity levels at weeks 8 and 12 were
      nearly twice as high in the G115 group as compared to the placebo group (p <
      0.0001). In all the volunteers, laboratory values of 24 safety parameters showed
      no significant differences between the end and the beginning of the 12-week study
      in either of the groups. There were only 9 adverse events in the study, the
      principal one being insomnia.

PMID- 8879983
TI  - The mammalian cell cycle in normal and abnormal growth.
AB  - Cell division, a complex array of intracellular events, occurs in a highly
      ordered and carefully coordinated manner. This regulation is achieved by the
      sequential activation and deactivation of the members of a family of serine
      threonine-specific protein kinases that consist of regulatory and enzymatic
      subunits, the cyclins and cyclin-dependent kinases. These enzymes, in turn,
      regulate the activity of other proteins involved in the mitogenic pathway.
      Mutations in the components of the regulatory pathways can lead to aberrant
      growth, including malignancies.

PMID- 8879984
TI  - Genomic imprinting in disorders of growth.
AB  - This review has briefly considered some of the vast amount of information that
      has been gathered on genomic imprinting and its role in PWS, AS, BWS and Russell
      Silver syndrome. The pace of investigation into the phenomenon of imprinting will
      undoubtedly continue, because our understanding remains far from complete. Newer
      approaches to identifying imprinted genes based on their expression rather than
      their location are likely to uncover currently unknown genes. We can also look
      forward to more insight into the fascinating complexities of the imprinting
      process.

PMID- 8879985
TI  - Role of Pit-1 in the gene expression of growth hormone, prolactin, and
      thyrotropin.
AB  - To date, nine different mutations in the Pit-1 gene resulting in CPHD have been
      described in mammals. Four of these mutations alter residues important for DNA
      binding or alter the predicted alpha helical nature of the Pit-1 protein (A158P,
      R172X, E250X, and W261C). The A158P mutation, however, has minimal effects on DNA
      binding. Four mutations lie outside alpha helical regions (P24L, R143Q, K216E,
      and R271W) and do not significantly alter DNA binding either experimentally or by
      prediction. One mutation is a large deletion of the Pit-1 gene locus in the
      Jackson dwarf mouse. Mutant Pit-1 proteins that do not interfere with binding
      cause CPHD through interference with target gene activation and regulation. The
      R271W mutant acts as a dominant inhibitor of transcription of the GH and Prl
      genes. The A158P mutant is incapable of activating transcription from the GH-I
      site and has low activation of transcription of the distal enhancer and proximal
      promoter sites of Prl and of 320 bp of the 5' GH promoter sequence. Some mutant
      proteins interfere with nuclear receptors. For example, the K216E mutant has
      defective retinoic acid signaling on the Pit-1 gene enhancer. There is phenotypic
      variability in the degree of CPHD and in pituitary size in patients with Pit-1
      gene mutations. Since Pit-1 has different functions in the somatotroph,
      lactotroph, and thyrotroph, it is not surprising that point mutations in
      different regions of the gene interfere in different ways with Pit-1 function. A
      mutant Pit-1 may be able to carry out its developmental role, but may be aberrant
      in GH and Prl gene activation or Pit-1 autoregulation. Study of Pit-1 mutations
      and their diverse pathophysiologic mechanisms should increase the understanding
      of anterior pituitary gland development and gene regulation in normal and disease
      states.

PMID- 8879986
TI  - The regulation of growth hormone secretion.
AB  - The regulation of GH secretion involves finely balanced systems with multiple
      components. As our knowledge of the physiology of GH regulation expands, so does
      our understanding of the bases for GH diseases. We now can identify several
      cellular loci that cause GH deficiency or GH excess. In addition, the recent
      increased understanding of GH physiology has resulted in an increase in potential
      therapies for growth disorders.

PMID- 8879987
TI  - Insulin-like growth factors and their receptors in growth.
AB  - The IGFs are essential stimulators of fetal and postnatal growth. Their signals
      are mediated predominantly by the type I IGF receptor, but another as yet
      unidentified receptor seems to mediate some actions, especially some of those for
      IGF-II. During organogenesis, the actions of IGF-I seem to be local
      (autocrine/paracrine), because it, as well as IGFBPs and IGF receptors, are
      expressed coordinately in a highly tissue and developmentally specific fashion.
      IGF-I, however, most likely assumes endocrine functions during postnatal life and
      provides signals for GH and nutritional status. On the other hand, IGF-II may
      have only local growth-promoting functions, and its most essential actions may be
      restricted to in utero life. Both IGFs may be involved in regenerative organ
      growth, and their uncontrolled expression, especially that of IGF-II, may be
      involved in the formation of some tumors. The previous conclusions are drawn
      mainly from in vitro and animal experiments. Although they are generally
      consistent with data in humans, it is most likely incorrect to extrapolate to man
      all of the conclusions drawn from the experiments in mice. Differences in
      placentation are so marked between mice and humans that an exclusive role for IGF
      II in human placental growth seems unlikely. On the other hand, it is reasonable
      to conclude that both IGFs are important stimulants of normal human fetal growth,
      that IGF-I is a more potent stimulator of human postnatal growth, and that the
      type I IGF receptor mediates most IGF actions in humans. The fact that no human
      growth disorders have been linked convincingly to lack of function mutations in
      IGF or IGF receptor genes suggests that such defects are lethal.

PMID- 8879988
TI  - The role of the insulin-like growth factor binding proteins and the IGFBP
      proteases in modulating IGF action.
AB  - Over the past few years, there has been an explosion of data in the scientific
      literature regarding the various components of the IGF axis. IGFBPs and related
      molecules are now believed to be critical elements in numerous cellular processes
      and key factors in several disease states related to abnormal tissue and somatic
      growth. Recently, the BP-Prs were included in this complex system, and their
      importance is being unraveled. The upcoming years will undoubtedly bring even
      more information on the molecular biology of these key cellular regulators. These
      discoveries are likely to lead to better understanding of growth and cellular
      regulation and to development of novel therapeutic approaches to a variety of
      diseases.

PMID- 8879989
TI  - The mechanisms by which growth hormone brings about growth. The relative
      contributions of growth hormone and insulin-like growth factors.
AB  - Growth hormone is the major regulator of postnatal growth. Although intrauterine
      growth seems to be largely growth hormone independent, gene knockout studies have
      established the pivotal role of the IGF system in both prenatal and postnatal
      growth. The original "somatomedin hypothesis" postulated that all of the growth
      promoting actions of growth hormone were mediated by IGFs. Several in vitro and
      in vivo studies have suggested, however, that growth hormone may have specific
      growth-related actions in addition to stimulating IGF production, including
      promoting differentiation of prechondrocytes at the growth plate and stimulation
      of synthesis of proteins involved in IGF transport and clearance. An integrated
      model of interrelated role(s) of growth hormone and IGF in skeletal growth is
      proposed.

PMID- 8879990
TI  - Insulin as a growth factor.
AB  - Various clinical syndromes illustrate the essential role of insulin in modulating
      somatic growth both in utero and after birth. The effect of insulin on growth is
      a consequence of direct effects transduced via its homologous receptor and post
      receptor signaling pathways and indirect effects on other modulators of growth,
      such as the growth hormone-IGF axis. Recent insights into the post-receptor
      mechanisms of insulin signaling provide a scientific framework for the
      distinction between the traditional role of insulin as a major modulator of
      metabolism and its role as a promoter of growth.

PMID- 8879991
TI  - The growth without growth hormone syndrome.
AB  - The phenomenon of growth without GH has been recognized for over a quarter of a
      century in various physiologic or near-physiologic situations, including the
      fetal state and obesity, and in various obviously pathologic states, including
      postsurgical resection of suprasellar/hypothalamic tumors, most notably
      craniopharyngiomas, and in acromegaloidism. The mechanism or mechanisms
      responsible for this fascinating clinical syndrome are unknown. The available
      data implicate, at least in some of these subjects, a role for hypothalamic
      injury leading to obesity and insulin resistance which, in turn, leads to
      elevated circulating concentrations of insulin to which the body retains
      mitogenic sensitivity. Alternatively, in other subjects with this syndrome,
      evidence exists to support the presence of a circulating as yet incompletely
      characterized potent growth-promoting factor which appears in the serum. Further
      studies of this syndrome should help to enhance our knowledge of the mechanisms
      governing both normal and abnormal human growth.

PMID- 8879992
TI  - Growth hormones and sex steroid interactions at puberty.
AB  - Puberty is a period of dynamic changes mediated by GH and the gonadal steroid
      hormones. Although these substances exert important independent effects, their
      interaction is vital to normal pubertal growth and development. This is supported
      by observations of blunted growth and diminished levels of GH and IGF-1 during
      adolescence in individuals with panhypopituitarism in whom adequate replacement
      with both hormones had not been achieved. The independent roles of androgens and
      estrogens in mediating the rise in GH secretion at puberty have been studied in
      individuals with complete androgen insensitivity and through the administration
      of nonaromatizable androgens and the use of selective androgen- or estrogen
      receptor blockade. The preponderance of evidence from studies of nonaromatizable
      (pure) androgens suggests that GH secretion is not enhanced as it is under the
      influence of testosterone. In addition, studies have shown increased GH secretion
      following androgen-receptor blockade and diminished GH release after estrogen
      receptor blockade. Together these studies suggest a facilitory role of estrogen
      receptor-mediated processes on GH secretion and IGF-1 production. If androgens
      influence the GH/IGF-1 axis, it is most likely by an inhibitory mechanism.
      Observations of delayed skeletal maturation and deficient bone mineralization in
      individuals with estrogen receptor defects or mutations of the aromatase gene
      demonstrate the essential role of estrogen in promoting normal bone maturation,
      the accrual and maintenance of BMD, and control of the rate of bone turnover.

PMID- 8879993
TI  - Molecular genetic basis of the human chondrodysplasias.
AB  - Considerable progress has been made in delineating the molecular genetic basis of
      the human chondrodysplasias. Two genes emerge as harboring mutations found in
      patients with the most common disorders. Mutations in the type II collagen gene
      account for most spondyloepiphyseal dysplasia and spondyloepiphyseal dysplasia
      like clinical disorders, whereas mutations in the fibroblast growth factor
      receptor 3 gene are responsible for achondroplasia, thanatophoric dysplasia, and
      hypochondroplasia. A substantial portion of remaining patients have mutations of
      the genes encoding cartilage oligomeric matrix protein or diastrophic dysplasia
      sulfate transporter.

PMID- 8879994
TI  - Growth suppression by glucocorticoid therapy.
AB  - Glucocorticoids exert multiple growth-suppressing effects, interfering with
      endocrine (e.g., endogenous GH secretion) and metabolic (e.g., bone formation,
      nitrogen retention, collagen formation) processes essential for normal growth.
      Relatively small oral doses of daily exogenous GC, alternate-day oral GC therapy,
      and even IC are capable of slowing growth in some children. These growth
      inhibiting and catabolic effects of GC can be variably counterbalanced by GH
      therapy. With regard to linear growth, GH responsiveness depends on the GC dose
      and severity of underlying GC-dependent disease. Short-term risks of combined GH
      and GC therapy are low; longer term risks (e.g., reduced allograft function,
      survival, or both; increased underlying disease activity; oncologic risk) require
      further study. GH therapy in GC-dependent children remains experimental; children
      considered for such treatment should be enrolled in studies that facilitate
      careful monitoring and collective data analysis.

PMID- 8879995
TI  - Effect of thyroid hormone on growth. Lessons from the syndrome of resistance to
      thyroid hormone.
AB  - Thyroid hormone deprivation results in deleterious effects on bone growth. The
      delayed bone development is mediated by a direct effect of thyroid hormone on
      bone and an indirect effect of the hormone on GH release and IGF-1 action. Both
      TR alpha and TR beta are expressed in bone cells. To examine the role of TR beta
      on bone, we have reviewed the growth abnormalities in the human syndrome of RTH
      caused by mutations in the TR beta gene. The mutant TR beta reduces the tissue
      responsiveness to thyroid hormone, producing in some tissues variable degrees of
      thyroid hormone deprivation. With regard to bone, relative thyroid hormone
      deficiency caused by the mutant TR beta produces short stature and delayed bone
      growth but does not attenuate growth to the extent that absolute thyroid hormone
      deficiency does. These observations indicate that an intact TR beta is required
      for normal bone development and growth.

PMID- 8879996
TI  - The effects of irradiation and chemotherapy on growth.
AB  - The effects of cancer therapy on growth are reviewed. The effects of radiation
      and chemotherapy on growth hormone production and growth hormone responsiveness
      by peripheral tissues are examined. The effects of radiotherapy and chemotherapy
      on other endocrine function pertaining to growth also are discussed. An approach
      to surveillance of pediatric cancer survivors pertaining to growth and
      development is suggested.

PMID- 8879997
TI  - Essentials of growth diagnosis.
AB  - There is more to growth than GH. Growth disorders can be approached expeditiously
      by assessing the relationships among height, weight, BA and height velocity.
      Undernutrition is indicated by low weight for height; diabetes mellitus,
      hyperthyroidism, and electrolyte disturbances are the major endocrine
      considerations. Short stature results from intrinsically short, delayed, or
      attenuated growth patterns. Excessive stature results from intrinsically tall,
      advanced, or accelerated growth patterns. Each of these patterns causing linear
      growth abnormalities has a distinct differential diagnosis that variously
      includes endocrine, metabolic, genetic, and systemic disorders.

PMID- 8879998
TI  - Current and potential therapeutic uses of growth hormone and insulin-like growth
      factor I.
AB  - The accepted and potential uses of GH and IGF-I are summarized in Table 1. In
      general, the research on the therapeutic uses of IGF-I is at a much earlier state
      of development compared with GH The use of GH in the treatment of children with
      GH deficiency is well accepted, and its use in the treatment of short stature of
      renal failure also is widely accepted. The FDA has approved the use of GH in
      children with short stature caused by GH insufficiency and renal failure. The use
      of GH in patients with Turner syndrome has not been approved by the FDA, although
      it has been approved in several other countries. The use of GH for the treatment
      of adults with GH deficiency is approved in several countries but it is not
      approved in the Unites States. With the exception of the cases with GHIS, the use
      of IGF-I as a therapeutic agent cannot yet be regarded as of proven usefulness.
      The potential uses of GH and IGF-I are an area of active investigation and will
      continue to enlighten our understanding of human disease and disorders of growth.

PMID- 8879999
TI  - Teplice program--the impact of air pollution on human health.
AB  - The aim of the Teplice Program is to investigate and assess the impact of air
      pollution on the health of the population in the district of Teplice, Czech
      Republic. Characterization of the air pollutants demonstrated unusually high
      concentrations during winter inversions of fine particles dominated by acidic
      sulfates, genotoxic organic compounds, and toxic trace elements. The major source
      of airborne fine particles is the burning of coal for heating and power. Human
      exposure and biomarker studies demonstrated large seasonal variations in air
      pollution within the Teplice District and higher seasonal average pollution
      levels than the comparative district, Prachatice. Personal exposures to fine
      particles and organic carcinogens [e.g., polycyclic aromatic hydrocarbons (PAH)]
      were correlated with excretion of PAH metabolites in urine, several trace metals
      in blood, and DNA adducts in white blood cells. Respiratory and neurobehavioral
      studies of school children were conducted using questionnaires and clinical
      measures. A significantly higher prevalence of adverse respiratory symptoms and
      decreased lung function were found in the Teplice district than in Prachatice.
      The neurobehavioral studies indicated significantly higher teacher referrals for
      clinical assessment in Teplice, but the majority of objective performance
      measures did not differ. Reproductive studies were conducted in both males and
      females. A study of the effects of exposure on pregnancy and birth found an
      excess prevalence of low birth weight and premature births in Teplice; these
      adverse effects were more common in infants conceived in the winter and whose
      mothers were smokers. Based on questionnaires and medical examination, the
      reproductive development of young men was not different between districts and
      seasons, however, measures of semen quality suggest that exposure to high levels
      of air pollution are associated with transient decrements in semen quality.

PMID- 8880002
TI  - Statement from the work session on chemically-induced alterations in the
      developing immune system: the wildlife/human connection.

PMID- 8880000
TI  - Research needs for the risk assessment of health and environmental effects of
      endocrine disruptors: a report of the U.S. EPA-sponsored workshop.
AB  - The hypothesis has been put forward that humans and wildlife species adverse
      suffered adverse health effects after exposure to endocrine-disrupting chemicals.
      Reported adverse effects include declines in populations, increases in cancers,
      and reduced reproductive function. The U.S. Environmental Protection Agency
      sponsored a workshop in April 1995 to bring together interested parties in an
      effort to identify research gaps related to this hypothesis and to establish
      priorities for future research activities. Approximately 90 invited participants
      were organized into work groups developed around the principal reported health
      effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity
      as well as along the risk assessment paradigm-hazard identification, dose
      response assessment, exposure assessment, and risk characterization. Attention
      focused on both ecological and human health effects. In general, group felt that
      the hypothesis warranted a concerted research effort to evaluate its validity and
      that research should focus primarily on effects on development of reproductive
      capability, on improved exposure assessment, and on the effects of mixtures. This
      report summarizes the discussions of the work groups and details the
      recommendations for additional research.

PMID- 8880003
TI  - Alterations in fetal thymic and liver hematopoietic cells as indicators of
      exposure to developmental immunotoxicants.
AB  - Recent studies indicate that immune development in humans and other species may
      be altered after perinatal exposure to immunotoxic environmental contaminants.
      However, limited information is available regarding appropriate tests that may
      adequately detect developmental immunotoxic compounds. Experiments in which
      pregnant laboratory rodents were exposed to a variety of immunotoxic
      environmental agents indicate that fetal thymus and liver immune cells may be
      quantitatively and qualitatively altered by immunotoxicant exposure and, thus,
      may serve as sensitive markers of developmental immunotoxicant exposure. In
      particular, depression of fetal thymic cell counts appears to be a common event
      following gestational exposure to immunotoxicants that produce this response in
      adult animals. Total hematopoietic cell counts in fetal liver, however, may be a
      poor indicator of immunotoxicant exposure. Altered marker expression in both
      fetal thymus and liver appears to be a highly sensitive indicator of gestational
      immunotoxicant exposure. Together, these reports suggest that immune tests with
      high predictability for immunosuppression in adults may also be appropriate for
      the detection of developmental immunotoxic agents.

PMID- 8880004
TI  - Effects of altered prenatal hormonal environment on expression of autoimmune
      disease in NZB/NZW mice.
AB  - F1 hybrid New Zealand Black (NZB) x New Zealand White (NZM) (NZB/NZW) mice
      spontaneously develop an autoimmune disease analogous to systemic lupus
      erythematosus (SLE). Testosterone experts a powerful suppressive effect on this
      disorder in adult NZB/NZW mice. A series of experiments was designed to determine
      if disease would also be suppressed by exposing fetal NZB/NZW mice to increased
      testosterone. A model was developed in which NZB dams carrying NZB/NZW fetuses
      were treated with testosterone in a dose adequate to masculinize the external
      genitalia in female fetuses. NZB/NZW mice that were derived from testosterone
      treated dams and control NZB/NZW offspring were followed in a longevity study and
      had serial assays to assess development of SLE. Additional experiments were
      carried out to measure lymphocyte subsets and responses to mitogens. Results were
      compared with F1 hybrid offspring of C57BL/6 dams crossed with DBA/2 males, which
      are not autoimmune and do not develop SLE. Spleen cells from these groups were
      tested for Thy 1.2, CD4, CD8, and IgM receptors, and for responses to the
      mitogens Concanavalin A (ConA) and lipopolysaccharide. Control male NZB/NZW
      fetuses had unexpectedly high serum estradiol, which decreased significantly with
      maternal testosterone treatment. The testosterone-exposed male NZB/NZW fetuses
      developed into adults that lived longer than male NZB/NZW controls. Testosterone
      treatment of the dam was associated with elevated terminal anti-DNA levels but
      did not alter markers of renal diseases in adult NZB/NZW mice of either sex.
      Testosterone-exposed NZB/NZW females had altered T-lymphocyte subsets and
      testosterone-exposed males had increased response to ConA compared to controls.
      In male NZB/NZW fetuses whose mothers were administered testosterone, the
      naturally high level of circulating estradiol observed in untreated male fetuses
      was decreased significantly. This decrease was associated with an increase in
      longevity. This unique observation has important implications for fetal exposure
      to endocrine disruptors in the environment.

PMID- 8880005
TI  - Impaired immunity in harbour seals (Phoca vitulina) exposed to bioaccumulated
      environmental contaminants: review of a long-term feeding study.
AB  - Mass mortalities among seals and dolphins inhabiting contaminated marine regions
      have led to speculation about a possible involvement of immunosuppression
      associated with environmental pollution. To evaluate whether contaminants at
      ambient environmental levels can affect immune function of seals, we carried out
      an immunotoxicological study under semifield conditions. Two groups of 11 harbour
      seals (Phoca vitulina) originating from a relatively uncontaminated area were fed
      herring from either the highly polluted Baltic Sea or the relatively
      uncontaminated Atlantic Ocean. Changes in immune function were monitored over a 2
      1/2-year period. The seals that were fed contaminated Baltic herring developed
      significantly higher body burdens of potentially immunotoxic organochlorines and
      displayed impaired immune responses as demonstrated by suppression of natural
      killer cell activity and specific T-cell responses. During a 2-week fasting
      experiment performed at the end of the feeding study, mobilization of
      organochlorines from the blubber did not lead to a strong increase of contaminant
      levels in the blood, and no enhancement of the existing immunosuppression was
      observed. These results demonstrate that chronic exposure to environmental
      contaminants accumulated through the food chain affects immune function in
      harbour seals, whereas short-term fasting periods, which are normal for seals, do
      not seem to pose an additional risk. The seals of this study were not exposed
      perinatally to high levels of environmental chemicals, and body burdens of
      organochlorines measured near the end of the study were lower than those
      generally observed in free-ranging seals inhabiting many contaminated regions.
      Therefore, it may be expected that environmental contaminants adversely affect
      immune function of free-ranging seals inhabiting contaminated regions at least as
      seriously as observed in these studies.

PMID- 8880001
TI  - Male reproductive health and environmental xenoestrogens.
AB  - Male reproductive health has deteriorated in many countries during the last few
      decades. In the 1990s, declining semen quality has been reported from Belgium,
      Denmark, France, and Great Britain. The incidence of testicular cancer has
      increased during the same time incidences of hypospadias and cryptorchidism also
      appear to be increasing. Similar reproductive problems occur in many wildlife
      species. There are marked geographic differences in the prevalence of male
      reproductive disorders. While the reasons for these differences are currently
      unknown, both clinical and laboratory research suggest that the adverse changes
      may be inter-related and have a common origin in fetal life or childhood.
      Exposure of the male fetus to supranormal levels of estrogens, such as
      diethlylstilbestrol, can result in the above-mentioned reproductive defects. The
      growing number of reports demonstrating that common environmental contaminants
      and natural factors possess estrogenic activity presents the working hypothesis
      that the adverse trends in male reproductive health may be, at least in part,
      associated with exposure to estrogenic or other hormonally active (e.g.,
      antiandrogenic) environmental chemicals during fetal and childhood development.
      An extensive research program is needed to understand the extent of the problem,
      its underlying etiology, and the development of a strategy for prevention and
      intervention.

PMID- 8880007
TI  - Polymorphisms of platelet receptors as risk factors in coronary thrombosis.

PMID- 8880008
TI  - Gene therapy--the state of play.

PMID- 8880006
TI  - Organochlorine-associated immunosuppression in prefledgling Caspian terns and
      herring gulls from the Great Lakes: an ecoepidemiological study.
AB  - The objectives of study were to determine whether contaminant-associated
      immunosuppression occurs in prefledgling herring gulls and Caspian terns from the
      Great Lakes and to evaluate immunological biomarkers for monitoring health
      effects in wild birds. During 1992 to 1994, immunological responses and related
      variables were measured in prefledgling chicks at colonies distributed across a
      broad gradient of organochlorine contamination (primarily polychlorinated
      biphenyls), which was measured in eggs. The phytohemagglutinin skin test was used
      to assess T-lymphocyte function. In both species, there was a strong exposure
      response relationship between organochlorines and suppressed T-cell-mediated
      immunity. Suppression was most severe (30-45%) in colonies in Lake Ontario (1992)
      and Saginaw Bay (1992-1994) for both species and in western Lake Erie (1992) for
      herring gulls. Both species exhibited biologically significant differences among
      sites in anti-sheep red blood cells antibody titers, but consistent exposure
      response relationships with organochlorines were not observed. In Caspian terns
      and, to a lesser degree, in herring gulls, there was an exposure-response
      relationship between organochlorines and reduced plasma retinol (vitamin A). In
      1992, altered White blood cell numbers were associated with elevated
      organochlorine concentrations in Caspian terns but not herring gulls. The
      immunological and hematological biomarkers used in this study revealed
      contaminant-associated health effects in wild birds. An epidemiological analysis
      strongly supported the hypothesis that suppression of T-cell-mediated immunity
      was associated with high perinatal exposure to persistent organochlorine
      contaminants.

PMID- 8880009
TI  - Is anticoagulation for intracoronary stenting justified?

PMID- 8880010
TI  - Treating the diabetic patient with coronary disease.

PMID- 8880011
TI  - Determinants of the acute phase response in acute myocardial infarction.

PMID- 8880012
TI  - Different significance of hyperventilation-induced electrocardiographic changes
      in healthy subjects and patients with coronary artery disease.

PMID- 8880013
TI  - Time to bid farewell to surgical mitral commissurotomy?

PMID- 8880014
TI  - The value of angiotensin converting enzyme inhibitors for the treatment of
      patients with left ventricular dysfunction, heart failure or after acute
      myocardial infarction.

PMID- 8880015
TI  - Prospects for gene therapy in cardiovascular disease.

PMID- 8880016
TI  - Interventional cardiology in Europe 1993. Working Group on Coronary Circulation
      of the European Society of Cardiology.
AB  - An annual survey on cardiac interventions in Europe is performed by the working
      group on Coronary Circulation of the European Society of Cardiology with the help
      of the national societies of cardiology. A questionnaire about cardiac
      interventions in 1993 was mailed to a representative of the national societies of
      35 members of the European Society of Cardiology. The data collection of coronary
      interventions was delayed by slow backreporting and from 10 of the 35 national
      members data were missing or grossly incomplete. They were excluded from the
      analysis. CORONARY ANGIOGRAPHY: A total of 756,822 coronary angiograms were
      reported resulting in an incidence of 1146 +/- 1024 per 10(6) inhabitants,
      ranging from 24 (Romania) to 3499 (Germany). This represents an increase of 12%
      compared to 1992. Germany (279,882 cases), France (157,237), the United Kingdom
      (77,000), Italy (44,934) and Spain (37,591) registered 79% of all the coronary
      angiograms performed. PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY: A total of
      183,728 percutaneous transluminal coronary angioplasty cases were reported in
      1993, 24% more than in 1992. On average, they accounted for 18 +/- 7% (range 8
      (Romania) to 35% (Sweden) of the coronary angiograms. Most of these percutaneous
      transluminal coronary angioplasties (82%) were confined to a single vessel. In
      13% only, percutaneous transluminal coronary angioplasty took place immediately
      after the diagnostic study. Adjusted per capita. Germany ranks first with 873
      percutaneous transluminal coronary angioplasties per 10(6) inhabitants, followed
      by France (737), Holland (725), Belgium (713), and Switzerland (665). The
      European mean of percutaneous transluminal coronary angioplasties per 10(6)
      inhabitants was 270 +/- 279, representing an increase of 14% compared with 1992.
      A major in-hospital complication was reported in 3.8% of the patients undergoing
      percutaneous transluminal coronary angioplasty: 0.6% hospital deaths, 1.5%
      emergency coronary artery bypass grafting, and 1.7% myocardial infarctions. NEW
      DEVICES: In 1993 stents were implanted in 6444 patients (3.5% of all percutaneous
      transluminal coronary angioplasty patients), equally distributed between bail-out
      situations (53%) and elective procedures. The 14 stent implanting countries
      showed a mean increase in incidence of coronary stenting of 53% compared with
      1992. Other interventional devices were applied in 7045 cases, 3.8% of all
      percutaneous transluminal coronary angioplasty cases. Coronary ultrasound (2194
      cases) and coronary angioscopy (380 cases) were performed infrequently. NON
      CORONARY INTERVENTIONS: Valvuloplasties were most frequently performed non
      coronary interventions European countries performed more than 300 valvuloplasties
      each in 1993. Most of them were mitral valvuloplasties in southern countries.
      CONCLUSIONS: Although partial backreporting might conclusions, several findings
      of this survey are noteworthy for the participating countries: The number of
      percutaneous taneous transluminal coronary angioplasties is universally
      increasing. There is an extremely wide range of coronary angiography and
      percutaneous translumina, coronary angioplasties performed per population. The
      most common additional procedure is a stent implantation while other new devices
      are only rarely applied. Mitral valvuloplasty is the most frequently performed
      non-coronary intervention.

PMID- 8880017
TI  - Tissue plasminogen activator, tissue plasminogen activator inhibitor and
      lipoprotein(a) in patients with coronary, epiaortic and peripheral occlusive
      artery disease.
AB  - In order to evaluate the relationship between the presence of atherosclerotic
      disease, documented by angiography, and the fibrinolytic profile, 262 consecutive
      patients affected by coronary (n = 90), epiaortic (n = 60) and peripheral (n =
      104) artery disease have been included in the study. Twenty-two healthy subjects
      were used as controls for laboratory parameters determination. All patients were
      classified on the basis of the presence (S+) or absence (S-) of clinically
      significant stenosis, according to specific scoring systems. Lipoprotein(a),
      plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA) and
      the PAI-1/t-PA ratio were significantly lower in controls than in coronary,
      epiaortic and peripheral artery disease patients. However, the levels of these
      parameters were not statistically different between S+ and S- subjects. These
      results confirm the association between lipoprotein(a), PAI-1 and t-PA levels and
      the presence of atherosclerotic disease independently of the arterial districts
      considered, while they do not appear to be directly linked to the severity of the
      morphological disease.

PMID- 8880018
TI  - Effects of insulin treatment on cause-specific one-year mortality and morbidity
      in diabetic patients with acute myocardial infarction. DIGAMI Study Group.
      Diabetes Insulin-Glucose in Acute Myocardial Infarction.
AB  - Diabetic patients with acute myocardial infarction have a poor prognosis, which
      has been attributed to a higher incidence of congestive heart failure and fatal
      reinfarction. This study reports on the one-year morbidity and mortality in a
      randomized study with the aim of testing whether insulin-glucose infusion
      initiated as soon as possible after onset of myocardial infarction and followed
      by long-term subcutaneous insulin treatment may have a beneficial effect on
      outcome in diabetic patients. In all, 306 patients were recruited to the insulin
      treated group, while 314 patients served as controls. The overall mortality after
      one year was 19% in the insulin group compared to 26% among controls (P < 0.05).
      The treatment effect was most pronounced in patients without prior insulin
      medication and at low cardiovascular risk. In this stratum the in-hospital
      mortality was reduced by 58% (P < 0.05) and the one-year mortality by 52% (P <
      0.02). The most frequent cause of death in all patients was congestive heart
      failure (66%), but cardiovascular mortality (congestive heart failure, fatal
      reinfarction, sudden death and stroke) tended to be decreased in insulin-treated
      patients. However, this difference did not reach the level of statistical
      significance. The number of reinfarctions was 53 (28% fatal) in the insulin group
      compared to 55 (45% fatal) in the control group. The two groups did not differ as
      regards need for hospital care or coronary revascularization during the year of
      follow-up. In summary, left ventricular failure and fatal reinfarctions
      contribute to increased mortality in diabetic patients following acute myocardial
      infarction. Intensive insulin treatment lowered this mortality during one year of
      follow-up.

PMID- 8880019
TI  - Serum C-reactive protein concentration in acute myocardial infarction and its
      relationship to mortality during 24 months of follow-up in patients under
      thrombolytic treatment.
AB  - OBJECTIVES: We studied the relationship between serum C-reactive protein and
      mortality in acute myocardial infarction. BACKGROUND: Early recanalization of an
      infarct-related coronary artery is considered to be an essential prerequisite for
      reducing mortality by thrombolytic treatment in acute myocardial infarction. It
      also reduces the inflammatory reaction caused by acute myocardial infarction and
      is measurable by determination of serum C-reactive protein concentrations. We
      therefore studied the prognostic value of determining serum C-reactive protein in
      acute myocardial infarction. METHODS: We measured serum C-reactive protein
      concentrations daily for 6 days and creatine kinase, as well as its MB isoenzyme
      concentrations twice a day, for 3 days after a myocardial infarct, in 188
      consecutive patients selected for thrombolytic therapy and treated in the same
      University Hospital Coronary Care Unit. The highest serum concentrations were
      related to total mortality as well as to the causes of death 3, 3-6, 6-12 and 12
      24 months after the onset of the myocardial infarction. RESULTS: The highest
      serum concentrations of serum C-reactive protein were observed 2 to 4 days after
      the onset of myocardial infarction. The mean value of the highest serum
      concentration of C-reactive protein in patients who survived the whole 24-month
      study period was 65 mg. 1(-1), with the 95% confidence intervals for the mean
      ranging from 58 to 71. The corresponding values in those who died within 3, 3-6,
      6-12 and 12-24 months were 166 (139-194), 136 (88-184), 85 (52-119) and 74 (38
      111) mg.1(-1), respectively. The values in those who died within 3 and 3-6 months
      of the infarction differed statistically significantly from the values in those
      who survived the whole period (P < 0.001 and P < 0.05, respectively). In patients
      who died due to congestive heart failure the mean highest serum C-reactive
      protein concentration was 226 (189-265) mg.1(-1). In those who suffered sudden
      cardiac death and those who died from a new myocardial infarction or non-cardiac
      causes, the respective values were 167 (138-196), 64 (38-89) and 48 (10-86) mg.
      1(-1). The values in those who died due to congestive heart failure and those
      suffering sudden cardiac death differed statistically significantly (P < 0.001)
      from the values of those who survived or died due to other causes. The highest
      serum concentrations of creatine kinase or its MB isoenzyme were not associated
      with mortality in this study. CONCLUSIONS: High serum C-reactive protein
      concentrations in acute myocardial infarction patients treated with thrombolytic
      drugs predict increased mortality up to 6 months following the infarction.
      Accordingly, reduction of inflammatory reaction by successful thrombolytic
      treatment may make an important contribution to the survival benefit of
      thrombolytic treatment of acute myocardial infarction.

PMID- 8880020
TI  - Comparison between abnormalities in segmental endocardial motion and
      abnormalities in segmental wall thickening after anterior myocardial infarction.
      A cine-magnetic resonance study.
AB  - In this study, two patterns of regional contract on of the left ventricle have
      been studied: endocardial motion and wall thickening, in order to check which of
      these was the most affected after myocardial infarction. The clinical relevance
      of this comparison was to assess which parameter of the regional contraction
      abnormality would best depict the severity of the infarction. Long axis cine
      magnetic resonance slices were used to assess segmental systolic left ventricular
      endocardial motion and segmental systolic wall thickening in 39 normal subjects
      and in 30 patients at the chronic stage of an anterior myocardial infarction. In
      the group of normal subjects, endocardial motion and wall thickening showed
      significant regional heterogeneity. Overall endocardial motion was greater than
      overall wall thickening: 9.5 +/- 2.0 mm vs 7.1 +/- 1.8 mm. P = 4 x 10(-12) (3.1
      +/- 1.2 mm vs 2.0 +/- 0.7 mm, P = 9 x 10(-5) after infarction). A significant
      linear correlation was found between these two parameters. In the infarction
      group, abnormality scores for endocardial motion and for wall thickening were
      calculated. These scores were defined as the average values exceeding the mean
      minus two standard deviations of the normal range for segments corresponding to
      the antero-septal-apical walls. The abnormality score for endocardial motion
      greater than the abnormality score for wall thickening: 0.31 +/- 0.12 vs 0.20 +/-
      0.07, P = 9 x 10(-4). We conclude that, in clinical practice, endocardial motion
      is affected to a greater degree by myocardial infarction than is wall thickening
      and therefore constitutes a more discriminant index in the assessment of post
      infarction patients.

PMID- 8880021
TI  - Acetylsalicylic acid may protect the patient by increasing fibrin gel porosity.
      Is withdrawing of treatment harmful to the patient?
AB  - The effect of acetylsalicylic acid in preventing cardiovascular complications is
      ascribed to acetylation of the enzyme cyclo-oxygenase thereby inhibiting
      prostaglandin synthesis. Acetylsalicylic acid, however, also acetylates
      fibrinogen. In the present pilot study, we investigated the permeability, i.e.
      porosity, of the fibrin gel in male patients with stable angina pectoris treated
      with this drug before and at 1 and 2 weeks after withdrawal. Ten patients were
      treated with 75 mg and eight with 160 mg. The results were compared to those in
      seven untreated healthy controls. Bleeding times were longer during treatment and
      were reduced after withdrawal indicating patient compliance. Fibrin gels were
      more porous during treatment although there were large inter-individual
      variations in porosity. One week after withdrawal, the porosity was reduced by 30
      41%, i.e. the network became tighter (75 mg group P = 0.001; 160 mg group P =
      0.002). The tightness was more pronounced after withdrawal than in the untreated
      controls. In conclusion, the protective effect of acetylsalicylic acid may be
      ascribed to its effect not only on platelets but also on fibrinogen. The
      withdrawal of acetylsalicylic acid may clause a markedly reduced fibrin gel
      porosity that we assume is disadvantageous in patients with cardiovascular
      disease.

PMID- 8880022
TI  - Percutaneous balloon mitral valvuloplasty in patients with mitral restenosis
      after previous surgical commissurotomy. A matched comparative study.
AB  - BACKGROUND: Although the efficacy of percutaneous balloon mitral valvuloplasty in
      patients with unoperated mitral stenosis has been well documented, there exists
      less clear-cut data on its effectiveness in patients with mitral restenosis after
      previous surgical commissurotomy. Accordingly, the purpose of this study was to
      evaluate our immediate and midterm results of balloon mitral valvuloplasty in
      this subset of patients with previous mitral surgery. METHODS: Between October
      1991 and August 1995, 29 consecutive patients with mitral restenosis after prior
      surgical commissurotomy (group 1) underwent Inoue balloon mitral valvuloplasty.
      They were matched on a patient-to-patient basis with regard to baseline mitral
      echocardiographic score mitral valve area, severity of angiographic mitral
      regurgitation and follow-up duration with 29 other patients with unoperated
      mitral stenosis (group 2) who underwent balloon mitral valvuloplasty during the
      same study period. RESULTS: Balloon mitral valvuloplasty yielded identical
      improvements in transmitral gradient and mitral valve area (from 0.8 to 1.6 cm2)
      determined echocardiographically, and similar changes in the severity of mitral
      regurgitation in both groups of patients. All procedures were successfully
      completed without major cardiac complications. Follow-up echocardiographic
      assessment in 73% of patients revealed equal mitral valve area (1.6 cm2) and a
      restenosis rate of 17%, with no difference in the restenosis rate between the two
      groups. CONCLUSION: Balloon mitral valvuloplasty in selected patients with mitral
      restenosis after past surgical commissurotomy can be performed safely and with
      similar immediate and midterm efficacy as in patients with de novo mitral
      stenosis.

PMID- 8880023
TI  - Combined antiplatelet therapy with ticlopidine and aspirin. A simplified approach
      to intracoronary stent management.
AB  - Intravascular metallic stents are increasingly used in the non-surgical
      management of coronary atherosclerosis. Despite intensive anticoagulation,
      subacute stent thrombosis, which usually has serious clinical consequences, and
      major haemorrhagic complications remain major problems after stent implantation.
      In addition, conventional management with anticoagulant therapy requires
      prolonged hospitalization. In a prospective multicentre study, we investigated
      the efficacy of a combination of two antiplatelet agents, ticlopidine 500 mg
      daily and aspirin 200 mg daily, without oral anticoagulation after stent
      implantation. Since November 1993, 529 consecutive patients, in whom 545 vessels
      were successfully stented with conventional (non-heparin coated) stents have been
      enrolled. Stenting was performed as a bailout procedure for failed angioplasty in
      112 patients, for a suboptimal result after angioplasty in 314 patients, and
      electively in the remaining 103 patients. Coronary events related, or possibly
      related, to stent thrombosis occurred in 5.4% of patients stented as a bailout
      procedure and in 1.8% of patients stented for a suboptimal result. Serious
      bleeding complications occurred in 5.4% of patients stented as a bailout
      procedure and 1.5% of patients stented for a suboptimal result. Neither stent
      thrombosis nor serious bleeding complications were seen in patients stented
      electively. Ticlopidine therapy was discontinued in 1.9% of patients due to
      neutropenia (0.6%) or rash (1.3%). Mean hospital stay decreased from 6.16 +/-
      2.14 days to 4.2 +/- 2.15 days during the study period. A combination of two
      antiplatelet agents can be employed in the vast majority of patients after
      coronary stent implantation. Subacute stent thrombosis rates and bleeding
      complications compare favourably with those reported using conventional therapy
      and the duration of hospitalization is reduced.

PMID- 8880024
TI  - Systemic thromboembolism in chronic heart failure. A prospective study in 406
      patients.
AB  - In patients with heart failure the risk of systemic thrombo-embolism and the
      benefit of anticoagulation are uncertain. To assess the incidence of systemic
      thromboembolism and the factors associated with an increased risk, 406
      consecutive patients with chronic heart failure were prospectively investigated.
      Their left ventricular ejection fraction was 23 +/- 8%, pulmonary wedge pressure
      19 +/- 10 mmHg and cardiac index 2.3 +/- 1.41. min-1.m-2 of body surface area.
      Two hundred patients were in NYHA functional class III-IV. Two hundred and thirty
      two patients were receiving oral anticoagulants. Over a follow-up period of 16 +/
      11 months, thromboembolism occurred in 11 patients (2.7%), seven of whom were on
      anticoagulants. Among clinical, echocardiographic and haemodynamic variables,
      atrial fibrillation, more severe haemodynamic impairment and low exercise
      capacity were associated with increased thromboembolic risk. No echocardiographic
      findings, including the presence of intracavitary thrombi, either at baseline or
      during follow-up, were related to subsequent thromboembolic events. The rate of
      embolism did not differ in patients receiving anticoagulants (4%) compared with
      those who did not receive anticoagulants (1%). No major bleeding occurred during
      follow-up. Thus, in patients with chronic heart failure and sinus rhythm the
      incidence of systemic thromboembolism is low regardless of anticoagulant
      treatment. Atrial fibrillation, particularly when associated with low cardiac
      index, identifies a subgroup of patients at high risk of events. In this
      subgroup, a moderate-intensity anticoagulant regimen provides unsatisfactory
      protection against thromboembolism.

PMID- 8880025
TI  - Mode of death in chronic heart failure. A request and proposition for more
      accurate classification.
AB  - The proportion of patients reported to die suddenly or from progressive
      circulatory failure is not consistent among studies of heart failure. Lack of an
      adequate or consistent classification of how patients die contributes to the
      current confusion over the mode of death in heart failure. Defining how patients
      with heart failure die could be important in developing strategies to reduce the
      continuing high mortality associated with this condition. We identified 27
      studies that reported 50 or more deaths among patients with heart failure to
      ascertain how death was classified. Definitions of sudden death appeared
      heterogeneous and the majority of studies failed to publish or make reference to
      how circulatory failure was defined. A framework for the classification of the
      mode of death has been developed in which clear separation of the activity and
      place at the time of death, cause of death, mode of death, and events prior to
      death is made (ACME: Activity, Cause, Mode and Event). This mode of classifying
      death has been successfully piloted in two mortality studies; AIRE and NETWORK.
      Classifying mortality in this way will help identify pathways leading to death
      and hence suggest therapies and strategies to reduce mortality in patients with
      heart failure, a group of patients whose prognosis remains poor.

PMID- 8880026
TI  - Flow velocity distributions in the left ventricular outflow tract and in the
      aortic annulus in patients with localized basal septal hypertrophy.
AB  - BACKGROUND: The velocity distributions in the left ventricular outflow tract and
      in the aortic annulus in normal subjects and certain cardiac patients are skewed,
      with the highest velocity along the anterior wall and septum. An abnormal
      anatomical structure of the interventricular septum changes the shape of the left
      ventricular outflow tract, and may consequently change the pattern of velocity
      distribution. METHODS: The cross-sectional velocity distributions in the left
      ventricular outflow tract and in the aortic annulus were constructed by using
      Doppler colour flow mapping in nine patients with localized basal septal
      hypertrophy, and in 10 normal subjects. The apical long axis view was used.
      RESULTS: In the studied patients, the velocity distributions in the left
      ventricular outflow tract and in the aortic annulus were skewed in a different
      way from those in normal subjects. The relative location of the maximal velocity
      on the cross-sectional diameter of the flow channel changed from one level to
      another. At the point of maximal basal septal hypertrophy, the velocity
      distribution was most skewed with the highest velocity along the anterior wall
      (e.g. basal septum). Distal to this level, the highest velocities of the skewed
      velocity profiles were gradually located closer to the central part of the flow
      channel. According to the time-velocity integral profile at the level of the
      aortic annulus, the pattern of skewness (in terms of the difference of the
      average time-velocity integrals between the anterior and posterior halves of the
      diameter) was significantly different between the normal and patient groups (5.51
      +/- 3.55 cm vs 0.03 +/- 2.07 cm; P < 0.01), while the extent of skewness (in
      terms of the ratio of the maximal to the cross-sectional mean time-velocity
      integrals) was close between two groups (1.36 +/- 0.28 vs 1.27 +/- 0.13; P >
      0.05). CONCLUSION: Localized basal septal hypertrophy significantly affects
      velocity distributions in the left ventricular outflow tract and in the aortic
      annulus.

PMID- 8880027
TI  - Idiopathic restrictive cardiomyopathy in childhood. A diastolic disorder
      characterized by delayed relaxation.
AB  - Six children with idiopathic restrictive cardiomyopathy were evaluated.
      Electrocardiographic evaluation disclosed left atrial dilatation and
      repolarization abnormalities. Echocardiographic examination showed gross left
      atrial enlargement (182 +/- 29% of predicted values, P < 0.001) in the presence
      of normal left ventricular cavity dimensions (99 +/- 6%, P: ns). Left ventricular
      wall thickness varied from normal to mild concentric hypertrophy (septum: 116 +/-
      16%, P < 0.05). Global left ventricular systolic function was normal or slightly
      subnormal; however, the relaxation was significantly delayed throughout diastole.
      E/A ratio was 4.1 +/- 1.4 and deceleration time 94 +/- 7 ms. Marked ventricular
      filling occurred in mid-diastole as could be deduced from a prominent mid
      diastolic mitral L wave on the Doppler flow tracing. Early filling contributed 56
      +/- 6%, mid-diastolic filling 28 +/- 4% and atrial contraction 16 +/- 3% to total
      ventricular filling as estimated by determining E-area, L-area and A-area,
      respectively. The left ventricular pressure curve showed a steady decline during
      mid-diastolic filling. This implies that the driving force for mid-diastolic
      filling is not the increased left atrial pressure but suction by the ventricle.
      The restrictive haemodynamics are therefore not caused by increased intrinsic
      stiffness of the ventricular wall, but most likely result from serious
      dysfunction and delay of the active relaxation of the ventricle. Progression of
      the disease was observed in three out of six patients, resulting in death or
      extreme low cardiac output. The three other patients remained clinically stable
      during the follow-up period of 6-10 years.

PMID- 8880028
TI  - Tetralogy of Fallot repair results in activation of the renin-angiotensin
      aldosterone system.
AB  - Fluid retention is a common problem following transannular patch repair of
      tetralogy of Fallot. The present study was undertaken to evaluate whether humoral
      substances may contribute to this process. Patients undergoing tetralogy of
      Fallot repair using a transannular patch technique were compared to patients
      undergoing simple ventricular septal defect repair. Hormone levels were
      determined by radioimmunoassay. Fluid retention was defined as pleural effusions
      persisting beyond 5 days. The data demonstrate that patients undergoing tetralogy
      of Fallot repair had elevated levels of anti-diuretic hormone, renin, angiotensin
      II, and aldosterone as compared to a group with ventricular septal defect. The
      elevation in hormone levels in the tetralogy of Fallot group was principally
      accounted for by those who developed effusions postoperatively. These results
      suggest that activation of the renin angiotensin-aldosterone system may be one of
      the contributing factors to fluid retention following tetralogy of Fallot repair.

PMID- 8880029
TI  - Female sex is associated with increased mortality and morbidity early, but not
      late, after coronary artery bypass grafting.
AB  - OBJECTIVE: To describe mortality and morbidity during a period of 2 years after
      coronary artery bypass grafting in relation to gender. DESIGN: Prospective follow
      up study. SETTING: Two regional cardiothoracic centres which performed all the
      coronary artery bypass operations in western Sweden at the time. SUBJECTS: A
      total of 2129 (1727 (81%) men and 402 (19%) women) consecutive patients
      undergoing coronary artery bypass surgery between June 1988 and June 1991 without
      concomitant procedures. RESULTS: Females were older and more frequently had a
      history of hypertension, diabetes mellitus, congestive heart failure, renal
      dysfunction and obesity. In a multivariate analysis, taking account of age,
      history of cardiovascular diseases and renal dysfunction, female sex appeared as
      a significant independent predictor of mortality during the 30 days after
      coronary artery bypass grafting (P < 0.05), but not thereafter. Various
      postoperative complications including neurological deficit, hydro- and pneumo
      thorax, perioperative myocardial damage and the need for assist devices and
      prolonged reperfusion were more common in females than males. CONCLUSION: Females
      run an increased risk of early death and the development of postoperative
      complications after coronary artery bypass surgery as compared with males. Late
      mortality does not appear to be influenced by gender and the long-term benefit of
      the coronary artery bypass graft operation is similar in men and women.

PMID- 8880030
TI  - Repolarization abnormalities with prolonged hyperventilation in apparently
      healthy subjects: incidence, mechanisms and affecting factors.
AB  - Brief hyperventilation is occasionally accompanied by repolarization
      abnormalities in subjects without apparent heart disease. However, the effect of
      prolonged hyperventilation on repolarization abnormalities is not clearly
      defined. We analysed the repolarization abnormalities induced by prolonged
      hyperventilation, correlated with hyperventilation induced haemodynamic changes
      and exercise test results and assessed the effect on them of age, gender, smoking
      and hypertension. Prolonged hyperventilation (overbreathing at least 30
      respirations/min for 5 min and 10 min recovery) was performed in 474 healthy
      volunteers (269 men, 205 women) 42.6 +/- 13.5 years old. The electrocardiogram
      was analysed for transient ST depression or T-wave inversion. Repolarization
      abnormalities were observed in 72 subjects, 47 men (17.5%) and 25 women (12.2%).
      Age, gender, smoking and hypertension did not influence the overall incidence of
      repolarization abnormalities. ST depression was more frequently observed in women
      (4.4 vs 0.7%, P < 0.01), while T wave inversion from negative to positive was
      more frequent in men (8.9 vs 2.4%, P < 0.006). All subjects with ST depression
      were non-smokers (4.1% of the non-smokers, P < 0.003 compared to smokers).
      Repolarization abnormalities occurred usually (80.5%), but not exclusively,
      within the first hyperventilation minute. Subjects with repolarization
      abnormalities developed higher heart rate change with hyperventilation than those
      without repolarization abnormalities (29.2 +/- 13.1 vs 24.2 +/- 12.7, P < 0.002).
      A positive exercise test was observed in 45.4% of subjects with hyperventilation
      induced ST depression but only in 13.1% of subjects with T-wave changes, P <
      0.02. Repolarization abnormalities are not uncommon during prolonged
      hyperventilation. Hear rate change affects the occurrence of repolarization
      abnormalities, while gender and smoking influence the type of repolarization
      abnormalities. ST depression but not T-wave inversion during hyperventilation is
      associated with a positive exercise test. Increased understanding about
      hyperventilation-induced repolarization abnormalities could affect use of the
      method in the clinic, either as a provocation test or as a complement to the
      interpretation of the exercise test.

PMID- 8880031
TI  - Slow bolus injection of ribose in the identification of thallium-201
      redistribution following combined adenosine/dynamic exercise stress.
AB  - AIM: A simple stress/redistribution thallium-201 myocardial perfusion imaging
      protocol may underestimate the degree of thallium redistribution in a defect
      identified on the stress images. We sought to investigate whether a slow-bolus
      injection of D-ribose improves the identification of thallium redistribution
      following combined adenosine/dynamic exercise stress. MATERIALS AND METHODS:
      Fifteen patients (10 males, five female, median age 63 years, range 50-75) were
      enrolled in the study. All underwent two successive adenosine plus exercise
      myocardial perfusion scintigraphy protocols 7-14 days apart. Adenosine was
      infused at 140 micrograms.kg-1.min-1 coupled with 25 W ergometer pedalling for 6
      min with 74 Mbq of thallium-201 being injected at 4 min. Immediately following
      the stress image acquisition, patients received the one of either 60 mg.kg-1 of D
      ribose or normal saline, injected over 5 min. Redistribution images were acquired
      after 4 h. The identical stress procedure was conducted in the crossover arm of
      the study, and patients received the alternative test article. SPECT images were
      visually analysed and scored in a nine segment model by two blinded observers. In
      addition, circumferential profile analysis was conducted. RESULTS: By visual
      interpretation 25 segments displayed redistribution of the ribose, but not in the
      saline study, 14 reversible segments were seen on the saline study alone and 18
      were seen on both studies (P = ns). In six patients ribose identified a greater
      number of redistributing segments and in a further six patients saline identified
      more reversible segments. Comparison of mean values of defect extent severity and
      percentage reversibility scores generated from the circumferential profile
      analysis showed no significant difference between the two arms of the study.
      CONCLUSION: A 5 min bolus injection of D-ribose following combined
      adenosine/dynamic exercise stress confers little benefit on the identification of
      redistribution of thallium-201. These results differ from those of previous
      studies which showed that a 30 min infusion of D-ribose following treadmill
      exercise significantly enhanced thallium redistribution. The duration of the
      ribose infusion is likely to be an important factor influencing the effect
      brought to bear on the redistribution of the tracer, and should be run over 30
      min, or longer.

PMID- 8880032
TI  - Survival analysis and clinical medicine. An observational comparison of the
      implantable cardioverter defibrillator, amiodarone treatment, and heart
      transplantation.
AB  - In clinical practice, observational studies remain necessary for evaluating
      accepted and new treatments. The comparison of results remains difficult and
      often controversial, because of a wide variation in clinical characteristics.
      Survival analysis and calculation of the standardized mortality ratio offer the
      possibility to compare outcomes in different study groups. We have applied these
      techniques to an observational comparison of outcomes in three groups of
      patients, followed in two university centres: (i) patients treated with an
      implantable cardioverter defibrillator; (ii) patients under amiodarone treatment;
      and (iii) recipients of a heart transplant. There was no statistically
      significant difference in the cumulative survival from total mortality. The
      standardized mortality ratio revealed the different natural history of patients
      undergoing heart transplantation.

PMID- 8880033
TI  - Impending paradoxical embolism and dynamic left ventricular outflow obstruction
      in a patient with recurrent pulmonary embolism and secondary pulmonary
      hypertension.

PMID- 8880034
TI  - Acute myocarditis mimicking myocardial infarction in an HIV infected patient.

PMID- 8880035
TI  - Autonomic dysfunction in hyperadrenergic orthostatic hypotension.

PMID- 8880036
TI  - Vitamin C status and respiratory function.
AB  - OBJECTIVE: To examine the cross sectional relationship between respiratory
      function and plasma vitamin C. DESIGN: Cross sectional analysis. SETTING:
      Population based study. SUBJECTS: 835 Men and 1025 women aged 45 to 75 registered
      with GP practices in Norfolk. INTERVENTIONS: Completion of health and lifestyle
      questionnaire and attendance for a health check. MAIN OUTCOME MEASURES: Forced
      expiratory volume in one second (FEV1), forced vital capacity (FVC) and non
      fasting plasma vitamin C. RESULTS: Plasma vitamin C was positively correlated,
      after adjustment for age and height, with both FEV1 (r = 0.17, P < 0.001) and FVC
      (r = 0.14, p < 0.001) in men. The association in women was weaker and not
      statistically significant. Adjusting for other possible factors and exclusion of
      various groups did not alter the observed associations. The differences in FEV1
      and FVC in men, adjusted for age, height and cigarette smoking, for a 50
      micromol/L difference in vitamin C were 0.22 litres (95% CI 0.10-0.33) and 0.23
      litres (95% CI 0.09-0.37) respectively. The population distribution was shifted
      such that 12.1% of men with vitamin C levels < or = 30 micromol/L had an FEV1 of
      less than two litres, compared with 4.6% with levels > or = 60 micromol/L.
      CONCLUSIONS: These findings are consistent with other studies of vitamin C and
      respiratory function and suggest that vitamin C may be protective for lung
      function through the whole normal range of dietary intake and lung function.

PMID- 8880037
TI  - The role of macronutrient selection in determining patterns of food intake in
      obese and non-obese women.
AB  - OBJECTIVE: Examination of the role of macronutrient selection in determining
      patterns of food intake in obese and non-obese women. DESIGN: Inventory: food
      intake diaries of two weekdays and one weekend day; EXPERIMENT randomized.
      SETTING: Inventory: in daily life. EXPERIMENT: department of Human Biology,
      University of Limburg. SUBJECTS: 68 subjects: 34 obese and 34 non-obese, age 20
      50 years, selected based on accurate completion of food intake diaries (< 10%
      underreporting); a sub-sample of 32 (16 obese and 16 non-obese) was assigned to
      the experiment. INTERVENTIONS: An ample choice of food items consisting of mainly
      one macronutrient each were offered 4 and 6 times per day, with different
      macronutrient compositions per day, ranging from 1-77 en% fat, 3-45 en% protein,
      and 19-96 en% carbohydrate. RESULTS: Selection, namely food choice that differs
      from random consumption, took place at breakfast in favour of carbohydrate, and
      at dinner in favour of fat. Habituation, namely a decreased response on the same
      stimulus, occurred after the fourth exposure to a single macronutrient buffet.
      For protein this was expressed as a significantly increased satiety score per kJ
      ingested; for fat as a significant drop in hedonic value; for carbohydrate as a
      significantly increased desire for a different taste, all (P < 0.05).
      Compensation, i.e. a correction afterwards for an earlier unusual macronutrient
      composition, resulting in a close to usual macronutrient composition of 24 h food
      intake, occurred at dinner, for a previous unusually low fat and high
      carbohydrate intake. CONCLUSIONS: A pattern of macronutrient intake was achieved
      by selection and compensation. Habituation occurred at the fourth exposure of a
      single macronutrient.

PMID- 8880038
TI  - The effects of monounsaturated-fat enriched diet and polyunsaturated-fat enriched
      diet on lipid and glucose metabolism in subjects with impaired glucose tolerance.
AB  - OBJECTIVE AND SUBJECTS: The effects of a high-fat, monounsaturated-fat enriched
      (Mono) diet and a reduced-fat, polyunsaturated-fat enriched (Poly) diet on lipid
      and glucose metabolism were compared in 31 subjects with impaired glucose
      tolerance. DESIGN AND INTERVENTIONS: After 3 weeks on a Run-in diet (37; 18:11:5,
      indicating energy percentages from total fat;
      saturated:monounsaturated:polyunsaturated fatty acids in the actual diets)
      subjects were randomized into a Poly-diet (34; 11:10:10) or a Mono-diet (40;
      11:19:8) for 8 weeks. RESULTS: In the Mono group fasting plasma glucose (mean +/-
      SD) was lower after the test diet than after the run-in period (6.4 +/- 1.3 vs
      6.0 +/- 0.8 mmol/L, 0 vs 8 weeks, P = 0.008), but remained unchanged in the Poly
      group (6.2 +/- 0.6 vs 6.1 +/- 0.7 mmol/L). Glucose effectiveness (SG), insulin
      sensitivity index and the first phase insulin response in an intravenous glucose
      tolerance test did not change significantly during either of the diets, but at
      the end of the study SG was higher in the Mono group than in the Poly group (P =
      0.013). Serum total cholesterol, LDL cholesterol, and apolipoprotein B decreased
      in the Mono group, while in the Poly group only serum total cholesterol decreased
      significantly. However, the mean changes in serum lipids and lipoproteins did not
      differ significantly between the groups. CONCLUSIONS: In free-living subjects
      with impaired glucose tolerance both the Mono-diet and the Poly-diet consumed
      after a saturated-fat enriched Run-in diet improved serum lipid profile and the
      Mono-diet seemed to improve glucose metabolism as well.

PMID- 8880039
TI  - Predictors of adipose tissue tocopherol and toenail selenium levels in nine
      countries: the EURAMIC study. European Multicentre Case-Control Study on
      Antioxidants, Myocardial Infarction, and Cancer of the Breast.
AB  - OBJECTIVE: To evaluate the levels of adipose tissue alpha-tocopherol, gamma
      tocopherol, and toenail selenium and their determinants. DESIGN: Control subjects
      from multicentre case-control study on antioxidants, myocardial infarction and
      cancer of the breast. SUBJECTS AND SETTING: 686 male and 339 female middle-aged
      and elderly subjects from eight European countries and Israel. RESULTS: The
      antioxidant levels were lower in men than women; adipose tissue alpha-tocophreol
      level in men was 75% of that in women, gamma-tocopherol 79% and toenail selenium
      92%, respectively. In multiple regression analysis adjusting for age and centre
      waist circumference showed to be the only independent predictor of adipose tissue
      alpha-tocopherol level and waist/hip (W/H) ratio that of gamma-tocopherol level
      in men. In women no predictors of adipose tissue alpha-tocopherol or gamma
      tocopherol level were found. Smoking and coffee use showed up to be the
      independent predictors of toenail selenium in men and smoking in women. Age,
      alcohol use, serum lipids, and reproductive factors were not related to the
      antioxidant levels. CONCLUSION: The inverse relationships of adipose tissue alpha
      tocopherol and gamma-tocopherol levels with central fat distribution should be
      considered in studies relating the tocopherol levels to the development of
      chronic diseases in men, and the inverse relationship of toenail selenium with
      smoking both in men and women, and with coffee consumption in men, should be
      considered when toenail selenium level is used as a biomarker in epidemiological
      studies.

PMID- 8880040
TI  - Total body protein status assessed by different estimates of fat-free mass in
      adult peritoneal dialysis patients.
AB  - OBJECTIVE: To assess the usefulness of fat-free mass (FFM) as an index of total
      body protein (TBPr) status in continuous ambulatory peritoneal dialysis (CAPD)
      patients. DESIGN: TBPr was measured by in vivo neutron activation analysis
      (IVNAA) and expressed as a standardised protein index (PI). FFM was estimated by
      dual energy X-ray absorptiometry (DXA), whole body counting of total body
      potassium (TBK), and creatinine kinetics (CK), and expressed as a standardised
      FFM index (FFMI). FFM was also determined by a criterion method based on four
      compartment model (4CM) which is defined as the sum of total body water
      determined by D2O dilution, TBPr determined by IVNAA, bone mineral determined by
      DXA, and glycogen estimated to be 4.4% of TBPr. Each patient was measured within
      a four hour period by all methods. SETTING: Body Composition Laboratory, Monash
      Medical Centre. SUBJECTS: Six male and twelve female CAPD patients (33-77 years).
      RESULTS: FFMI assessed by DXA and by TBK agreed with measurements of PI on
      identifying the mean TBPr status of the CAPD group as significantly below a
      comparable normal reference population (mean Z score: PI = -1.01 (P < 0.05); FFMI
      by DXA = -0.50 (P < 0.05); FFMI by TBK = -1.24 (P < 0.05)). In contrast, FFMI
      assessed by CK did not reveal a significantly reduced TBPr status (mean Z score: 
      0.70 (NS)). Furthermore, significant linear correlations were noted between PI
      and FFMI estimated by DXA and by TBK (r = 0.57 (P < 0.05) vs r = 0.69 (P < 0.05))
      however no significant correlation was observed between PI and FFMI estimated by
      CK (r = 0.36 (NS)). Moderate variation in FFM hydration did not compromise the
      ability of DXA, TBK or CK to differentiate between protein deleted, normal and
      enriched patients. Comparison of FFM estimates between the criterion method and
      either DXA, TBK or CK revealed no significant bias (+ 1.8 kg vs -2.0 kg vs +0.8
      kg) and respective SEE values of 3.8 kg (8.3%), 5.9 kg (14.3%) and 9.6 kg
      (21.7%). CONCLUSION: The findings of this study indicate that FFM estimated by
      either DXA or the whole body counting of TBK is a useful index of TBPr status in
      CAPD patients. However, FFM assessed by CK does not appear to be an appropriate
      index of TBPr status in CAPD patients.

PMID- 8880041
TI  - Postprandial triacylglycerolaemia: the effect of low-fat dietary treatment with
      and without fish oil supplementation.
AB  - OBJECTIVE: This study investigated whether a low-dose of fish oil had the ability
      to prevent the adverse effects associated with low-fat dietary treatment, namely
      elevated plasma triacylglycerol (TAG) and reduced high density lipoprotein (HDL)
      cholesterol concentrations. DESIGN: Thirty-two healthy volunteers participated in
      the trial, which consisted of four study groups (n = 8): low-fat diet with fish
      oil supplementation, low-fat diet without fish oil supplementation, full-fat diet
      with fish oil supplementation and full-fat diet without fish oil supplementation.
      Low-fat dietary treatment reduced dietary energy derived from fat by at least 10%
      and the low-dose of fish oil provided 1 g n-3 polyunsaturated fatty acids (PUFA)
      daily. The postprandial response to a fat-rich test meal (0.5 g/kg pre-trial body
      weight) was investigated before and after 16 weeks dietary intervention. RESULTS:
      Fasting plasma TAG concentrations were significantly (P < or = 0.05) reduced by
      fish oil supplementation and significantly (P < or = 0.05) increased by the low
      fat diet alone but not significantly affected following the low-fat diet with
      fish oil supplementation. The postprandial TAG response was significantly (P < or
      = 0.05) increased following the low-fat diet with fish oil supplementation.
      CONCLUSION: This study demonstrated that some of the deleterious effects of a low
      fat diet, reduced concentrations of the cardioprotective HDL2 cholesterol
      fraction and increased fasting plasma TAG concentrations were prevented when a
      low dose of fish oil was provided with a low-fat diet. However postprandial
      triacylglycerolaemia is adversely affected when the low-fat diet was supplemented
      with fish oil.

PMID- 8880042
TI  - Effect of fat- and sucrose-containing foods on the size of eating episodes and
      energy intake in lean dietary restrained and unrestrained females: potential for
      causing overconsumption.
AB  - OBJECTIVE: This study compared the action of high fat and high sucrose foods on
      snack size (satiation) and post snack satiety, in dietary unrestrained (UR) and
      restrained (R) lean females. DESIGN: 2 x 2 within-subjects design, each subject
      received each of four conditions in a counter-balanced order. SETTING: The Human
      Appetite Research Unit. SUBJECTS: 10 R and 10 UR lean young female students.
      INTERVENTIONS: Subjects consumed a low (1678 kJ) or high (2971 kJ) energy lunch,
      followed 2 hours later by an ad libitum snack consisting of a selection of high
      fat, low sucrose or high sucrose, low fat foods. Visual analogue rating scales
      recording subjective feelings of appetite were completed periodically. RESULTS:
      Energy intake at the snack was related to level of hunger (P < 0.01) and snack
      macronutrient composition (P < 0.001). Subjects consumed more energy when offered
      high fat snack foods, and more following a low energy lunch. Total group energy
      intake of the high fat snack selection following the low and high energy lunch
      was 4.39 and 3.63 MJ respectively, energy intake of the high sucrose snack
      selection following the low and high energy lunch was 3.03 and 2.81 MJ
      respectively. Post snack satiety was similar. Mean test day energy intake
      (including standard breakfast, fixed lunch, test snack and rest of day intake)
      was least when a low energy lunch was followed by an ad libitum snack of high
      sucrose foods. Some differences were seen between R and UR. R consumed more
      energy at the high fat snack following a low energy lunch, but not a high energy
      lunch. UR consumed more of the high fat snack following both lunch types. R
      consumed less energy (excluding alcoholic drinks) over the test day than UR (P <
      0.05), and also less on the day following the study day (P < 0.05). R generally
      rated themselves as lower on measures of appetite, and rated the high fat snacks
      as more pleasant. CONCLUSIONS: These results indicate the energy intake of an
      eating episode is related to hunger level and macronutrient composition of foods
      consumed. High fat foods give rise to higher current energy intake than high
      sucrose foods, and kilojoule for kilojoule are less effective in suppressing
      subsequent food intake.

PMID- 8880043
TI  - Anaemia among 6 year old children in the United Arab Emirates.
AB  - OBJECTIVE: The aim of this study is estimating the prevalence of anaemia among 6
      year old children in United Arab Emirates (UAE). DESIGN: Cross-sectional study.
      SUBJECTS: All new entries school children aged 6-6.9 years in six Emirates of UAE
      for the school year 1994/1995. The total children included were 11,800 (92% of
      total entries). MEASUREMENTS: Haemoglobin concentration in blood. Anaemia was
      determined using WHO criteria (< 12 g/dl). RESULTS: The total prevalence of
      anaemia was 31%. Boys were more susceptible than girls (P < 0.001), and national
      children were more likely to have anaemia than non-nationals (P < 0.001).
      CONCLUSIONS: Although the prevalence of anaemia has declined during 1981-1995,
      the current percentage of anaemia does not match with high socio-economic status
      and high coverage of health care in UAE.

PMID- 8880044
TI  - Pharmacotherapeutic education through problem based learning and its impact on
      cognitive and motivational attitude of Indian students.
AB  - OBJECTIVE: The cognitive and motivational attitudes to problem based learning
      (i.e., simple didactic problem stated in written form and Programmed Patient) has
      been compared with those to didactic lectures (DL), the traditional teaching
      method. The change in recall performance measured in MCQ tests was considered as
      a change in the cognitive domain. The first test was conducted one week after
      completion of the topic and second test was taken 3 months later, without prior
      information. The motivational change was recorded by open-ended questions about
      the learning method. Three groups of students at second MBBS professional year
      level consisting of 55, 57 and 59 people, were assigned a simple didactic problem
      stated in written form (SDP), programmed patients (PP), and didactic lecture
      (DL), respectively. RESULTS: The average scores obtained by the learners in
      problem based learning (PBL) groups were similar to the students in the DL group
      in both the tests. Most of the students in PBL groups appreciated the exercise
      and suggested including more such exercises in the curriculum. These exercises
      helped them to better understand patient problems and prescribing behaviour as
      well as in development of communication skills. However, these exercises were
      time consuming and were not examination oriented. CONCLUSION: Pharmacotherapeutic
      teaching through PBL could be used within a traditional curriculum to develop
      relevant and rational use of drugs, provided the evaluation method was also
      modified.

PMID- 8880045
TI  - Nucleoside transport inhibition by draflazine in unstable coronary disease.
AB  - OBJECTIVES: In a randomised, double-blind, placebo controlled study, we evaluated
      the tolerability and safety of draflazine, a nucleoside transport inhibitor, in
      the treatment of patients with unstable angina and non-Q-wave infarction.
      METHODS: Twenty-one patients were randomised to treatment with draflazine 3.5 mg
      or matching placebo given as an i.v. infusion and haemodynamic and symptomatic
      tolerability were investigated. Myocardial ischaemia was evaluated by means of
      vectorcardiography and blood analysis of the MB fraction of creatine kinase.
      RESULTS: The study drug was well tolerated by all patients and it did not cause
      any adverse haemodynamic effects, nor other serious adverse events. Three
      patients in the placebo group reported five adverse events, as compared to a
      single adverse event in the draflazine group. Cardiovascular events were detected
      in 7 patients in the placebo group and in 5 patients receiving draflazine. The
      mean duration of chest pain during the 24 hour observation period was 91.4 min in
      the placebo group compared to 75.5 min in draflazine treated patients. Neither
      the vectorcardiographic nor biochemical measures of ischaemia differed between
      treatment groups. CONCLUSION: Nucleoside transport inhibition by draflazine was
      well tolerated by patients with unstable coronary disease. It seems to be a
      promising method of adenosine enhancement in acute myocardial ischaemia. The
      potential cardioprotective effect of the drug needs further evaluation in larger
      trials.

PMID- 8880046
TI  - Postmarketing study of the use of flunarizine in vestibular vertigo and in
      migraine.
AB  - OBJECTIVE: This international postmarketing observational study of flunarizine
      was designed to evaluate, in routine clinical practice, the risk/benefit ratio of
      flunarizine in its approved indications, namely prophylaxis of migraine and
      treatment of vertigo. Comparator drugs were propranolol in migraine and
      betahistine in vertigo. The study was carried out by 498 general practitioners in
      Belgium, The Netherlands and Germany, whose participation had been requested by
      mail. In total 3186 patients were entered: 1601 in the two migraine cohorts and
      1585 in the two vertigo cohorts. RESULTS: In the migraine study, treatment
      results with propranolol tended to be somewhat better than those with
      flunarizine, but a selection bias cannot be excluded. There was no clear
      difference regarding efficacy between flunarizine and betahistine in the vertigo
      study. The safety evaluation focused on extrapyramidal symptoms (EPS) and
      depression. Overall, EPS were noted in only four patients, two in the vertigo
      betahistine and two in the migraine-flunarizine cohort. A total of 70 patients
      developed depressive symptoms (34 in the flunarizine and 24 in the propranolol
      migraine cohorts, but only 7 in the flunarizine and 5 in the betahistine vertigo
      cohorts). Patients with migraine were clearly more prone to depression than
      patients with vertigo, regardless of their treatment. Additional risk factors for
      depression were a history of depression, and, in the migraine flunarizine cohort,
      a high number of previous migraine treatments.

PMID- 8880047
TI  - Variability in the rate of 6-mercaptopurine methylation in the erythrocytes,
      liver and kidney in an Italian population.
AB  - OBJECTIVE: The polymorphism of erythrocyte thiopurine methyltransferase (TPMT) is
      genetically regulated as an autosomal codominant trait, and so should be
      congenital. RESULTS: We tested this hypothesis by measuring TPMT activity in
      erythrocyte preparations from adults and newborns and observed polymorphic
      distribution of TPMT activity in the adult and newborn erythrocytes. The activity
      of TPMT was higher in red cells from the newborns than adults. The frequency
      distribution of TPMT activity was also investigated in the liver and kidney. In
      the kidney, TPMT activity fell into two subgroups, whereas in the liver the
      distribution pattern was more complex. The activity of TPMT in erythrocytes and
      liver from the same subject was correlated, but the values of only half the cases
      fell within the 95% confidence limits, suggesting that the control of hepatic
      and/or erythrocyte TPMT is multifactorial.

PMID- 8880048
TI  - Assessment of analgesia in man: tramadol controlled release formula vs. tramadol
      standard formulation.
AB  - OBJECTIVE: The present study tested analgesia produced by a new controlled
      release formulation of tramadol. The investigation employed an experimental pain
      model based on chemo-somatosensory event-related potentials (CSSERP) in response
      to painful chemical stimuli applied to the nasal mucosa. STUDY: Twenty healthy
      volunteers participated in the experiments, which followed a controlled,
      randomised, double-blind, 3-way cross-over design. Each of the three medications
      (tramadol 100 mg [T100], tramadol controlled release 100 mg [TCR100] and tramadol
      controlled release 150 mg [TCR150]) was administered orally to fasting subjects.
      There was at least a 6 day washout period between tests. Each experiment was
      divided into five sessions, which took place before and 2, 4, 6, and 12 h after
      drug administration. In addition to the assessment of CSSERP, subjects rated the
      intensity of both the tonic and phasic painful stimuli. Nonspecific drug effects
      were also monitored by means of frequency analysis of the spontaneous EEG,
      ratings of adverse effects, and the subjects' performance in a tracking task.
      RESULTS: The significant reduction of amplitude N1 at central recording positions
      indicated that TCR 150 was the most effective analgesic 12 h after
      administration. Both 6 and 12 h after administration TCR 100 was more effective
      in terms of analgesia compared to T100. In addition, TCR100 appeared to produce
      fewer adverse effects than the standard formulation of tramadol. CONCLUSIONS: The
      controlled release formulation can be expected to become a valuable tool in
      peroral therapeutic regimens for chronic pain.

PMID- 8880049
TI  - Effect of nifedipine on superior mesenteric artery impedance in humans.
AB  - OBJECTIVE: In a randomized, double-blind placebo-controlled study the acute
      effect of sublingual nifedipine (10 mg) on the superior mesenteric artery
      pulsatility index (p.i.) was studied over 60 min in 12 healthy subjects (Age 43
      y). METHODS: p.i. was considered as a parameter of vascular resistance and was
      calculated as the peak-to-peak amplitude of the waveform divided by the mean
      amplitude. p.i. measurements were performed with the subject resting and fasting
      and were made 5, 10, 15, 30, 45 and 60 min for 1 hour after nifedipine (10 mg) or
      placebo. Arterial blood pressure and heart rate were measured at the same times.
      RESULTS: Placebo administration failed to change arterial blood pressure, heart
      rate or p.i. 5 min after 10 mg sublingual nifedipine, p.i. had significantly
      decreased from 5.0 to 3.8, with a nonsignificant decrease in arterial blood
      pressure and an increase in heart rate. By 15 min after nifedipine administration
      p.i. had further decreased to 3.1, and there was a concomitant significant
      decrease in mean arterial blood pressure and increase in heart rate. Sixty
      minutes after drug intake p.i. and arterial blood pressure were still below
      baseline not significant but the heart rate remained significantly increased.
      CONCLUSION: Our data indicate that in healthy subjects sublingual administration
      of nifedipine had a vasodilator effect (decrease in p.i.) on the superior
      mesenteric vascular bed.

PMID- 8880050
TI  - Oral therapy with combined enalapril, prazosin and hydrochlorothiazide in the
      acute treatment of severe hypertension in Nigerians.
AB  - OBJECTIVE: The efficacy, safety, tolerability and speed of onset of the
      hypotensive action of the combination of oral enalapril (10 mg) prazosin (1 mg)
      and hydrochlorothiazide (50 mg) has been assessed in 12 Nigerians with severe
      hypertension (Diastolic BP > or = 115 mmHg). PATIENTS: The ages of the patients
      ranged from 30-60 years, and the serum creatinine from 52-732 mumol.l-1. The
      initial blood pressure was 200/130 mmHg. RESULTS: The combination significantly
      reduced systolic and diastolic blood pressure respectively. The hypotensive
      action appeared within 0.5 h and led to a fall in BP to 175/120 mmHg, and the
      peak action occurred at 4 h, when the BP was 138/99 mmHg, and it persisted upto
      24 h (160/101 mmHg). Despite the significant fall in blood pressure, no reflex
      tachycardia was observed. Transient dizziness was seen in 2 patients, but
      otherwise all claimed improvement in clinical status and a clearer sensorium.
      CONCLUSION: The combination may be a useful oral treatment for the rapid control
      of severe hypertension in Blacks.

PMID- 8880051
TI  - Lack of effect of the serotonin4 receptor agonist zacopride on ACTH secretion in
      normal men.
AB  - OBJECTIVE: In the present study, we investigated the effect of zacopride on
      corticotropin (ACTH) and cortisol secretion in healthy volunteers. Male subjects
      received a single oral dose of placebo, 10 micrograms zaco-pride or 400
      micrograms zacopride. Plasma ACTH, cortisol and aldosterone concentrations were
      measured before and during the 3 h following the administration of the drug.
      RESULTS: For none of the doses did zacopride cause any modification of plasma
      ACTH or cortisol levels. In contrast, administration of 400 micrograms zacopride
      induced a significant increase in plasma aldosterone levels. CONCLUSION: Our
      results indicate that in humans serotonin-evoked stimulation of ACTH secretion is
      not mediated through serotonin4 (5-HT4) receptors. Together with previous
      findings, these data indicate that the stimulatory effect of 5-HT4 receptor
      agonists on aldosterone secretion in man can be ascribed solely to a direct
      action on glomerulosa cells.

PMID- 8880052
TI  - Comparison of the pharmacodynamic effects of deflazacort and prednisolone in
      healthy subjects.
AB  - OBJECTIVE: Deflazacort, a synthetic oxazoline derivative of prednisolone, has
      been suggested as having major advantages over other glucocorticoids, as it is
      claimed to cause fewer adverse effects at equivalent antiinflammatory potency.
      The assumed equipotency ratio of deflazacort versus other glucocorticoids is
      critical for this assumption. METHODS: In a randomized cross-over study we
      compared the acute effects of deflazacort and prednisolone on serum cortisol,
      osteocalcin, insulin and blood cells (eosinophils and lymphocytes) in normal
      subjects. On seven occasions separated by a wash out period > or = 1 week all
      participants received placebo, prednisolone (8 mg, 20 mg, 40 mg) and deflazacort
      (12 mg, 30 mg, 60 mg). The medication was given orally at 20.00 h as a single
      dose. Blood was collected at 8.00 h before and after each medication. Log (dose)
      response relationships were calculated and were used to compare the drugs.
      RESULTS: The following equipotent dose ratios (mg deflazacort: mg prednisolone)
      were found: osteocalcin suppression 1.54, cortisol suppression 2.27, suppression
      of eosinophils 1.14 and lymphocytes 2.77. As parallelism between regression
      curves was rejected, equipotency could not be calculated for insulin. In 3
      subjects even the highest dose of deflazacort failed to suppress serum cortisol.
      CONCLUSION: Our study highlights the difficulties of establishing equipotency
      ratios for glucocorticoids. It casts doubts on the generally assumed equipotency
      dose ratio of deflazacort vs prednisolone, as both for cortisol and lymphocytes
      the 95% CI was > 1.2. Thus, reduced adverse effects during deflazacort therapy
      may be a consequence of lower effective glucocorticoid dosage.

PMID- 8880053
TI  - Population pharmacokinetics and pharmacodynamics of oral levodopa in parkinsonian
      patients.
AB  - OBJECTIVE: The population pharmacokinetics and pharmacodynamics of a standardised
      oral test dose of levodopa have been determined in patients with mild to severe
      Parkinson's disease using parametric, non-linear mixed effect modelling with the
      program NON-MEM. Levodopa plasma concentration data and motor effect behaviour
      (tapping times) were obtained from 46 patients, for whom a total of 970
      observations were available (approximately 21 pharmacokinetic and pharmacodynamic
      observations per patient). The pharmacokinetic-pharmacodynamic model used was a
      one-compartment first-order absorption model linked to the sigmoid EMax
      representation of the Hill equation via an equilibration rate-constant, ke0. The
      model was also tested via a reduction in the number of pharmacokinetic and
      pharmacodynamic data points to a total of four to eight per patient. RESULTS: In
      the final regression models the Hoehn and Yahr (HY) status of the patient and
      duration of disease (DUR) were found to be important determinants of the
      pharmacodynamic parameters for levodopa. The pharmacokinetic parameters were not
      significantly affected by any covariates. A test group of 16 additional
      parkinsonian patients was used to evaluate the predictive performance of the
      population parameters. The predictive performance of the pharmacokinetic
      pharmacodynamic modelling using the full and reduced data sets was evaluated in
      NONMEM using posthoc, Bayesian forecasting. Statistically insignificant bias
      existed among predicted and observed levodopa concentrations, whereas the
      pharmacodynamic model underpredicted the observed tapping times. There was little
      difference in the pharmacokinetic-pharmacodynamic predictive performance among
      results for the full and the reduced data sets. CONCLUSION: In a clinical setting
      knowledge of the population pharmacokinetic and pharmacodynamic parameters for
      oral levodopa may prove useful in estimating the duration of the drug's
      beneficial motor activity in patients with mild to severe Parkinson's disease
      (Hoehn and Yahr status I-IV).

PMID- 8880054
TI  - Non invasive in vivo study of the maturation of CYP IIIA in neonates and infants.
AB  - OBJECTIVE: Cytochrome P450 III (CYP III) has previously been demonstrated in
      vitro in fetal liver. METHODS: A study was performed in 7 premature, 13 term
      neonates and 30 infants to assess whether or not maturation had any influence on
      CYP IIIA activity in children from birth to 1 year of age. A simple non invasive
      procedure was used (6 beta OHF/FF concentration ratio in a morning spot urine
      sample). RESULTS: The 6 beta OHF/FF ratio was 7.2, 7.9 and 5.0 in premature and
      term neonates and infants, respectively. CYP IIIA activity is present at birth,
      with a 6 beta OHF/FF ratio comparable to adults. Its activity seemed lower in
      infants. This might be due to the decrease in CYP IIIA7 activity during
      maturation after birth, which might be more rapid than the increase in CYP
      IIIA3/4 activity.

PMID- 8880055
TI  - Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram,
      fluoxetine, fluvoxamine and paroxetine.
AB  - OBJECTIVE: The purpose of this pharmacokinetic study was to investigate the dose
      dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four
      marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine,
      fluvoxamine and paroxetine. METHODS: The study was carried out as an in vivo
      single-dose study including 24 young, healthy men. All volunteers had been
      identified as sparteine- and mephenytoin-extensive metabolisers. The volunteers
      received in randomised order, at weekly intervals, increasing single oral doses
      of one of the four SSRIs, followed 3 h later by sparteine (CYP2D6), mephenytoin
      (CYP2C19) and caffeine (CYP1A2) tests. Fluoxetine was given at 3-week intervals
      because of the long half-life of fluoxetine and its metabolite norfluoxetine.
      Citalopram, fluoxetine and paroxetine were given in doses of 10, 20, 40 and 80 mg
      and fluvoxamine was given in doses of 25, 50, 100 and 200 mg. RESULTS: With
      increasing doses, there was a statistically significant increase in the sparteine
      metabolic ratio (MR) (P < 0.01, Page's test for trend) for all four SSRIs. The
      increase was modest after intake of citalopram and fluvoxamine, while the
      increase was more pronounced after fluoxetine intake, although no volunteers
      changed phenotype from extensive metabolisers to poor metabolisers. Three of the
      six volunteers changed phenotype from extensive metabolisers to poor metabolisers
      after intake of 40 or 80 mg paroxetine. There was a statistically significant
      increase in the mephenytoin S/R ratio (P < 0.01, Page's test for trend) with
      increasing doses of fluoxetine and fluvoxamine, but not after citalopram and
      paroxetine. However, no volunteers changed phenotype from extensive to poor
      metabolisers of S-mephenytoin. After intake of fluvoxamine, the urinary excretion
      of the metabolites related to N3 demethylation of caffeine were below the limit
      of quantification, whereas there were no significant changes in the urinary
      caffeine metabolic ratios after intake of the other three SSRIs. CONCLUSION: This
      investigation confirms that paroxetine and fluoxetine are potent inhibitors of
      CYP2D6, that fluvoxamine and fluoxetine are moderate inhibitors of CYP2C19 and
      that fluvoxamine is a potent inhibitor of CYP1A2 in humans in vivo. The clinical
      prediction of interaction from single-dose experiments may have to take the
      degree of accumulation during steady-state after multiple doses into account.

PMID- 8880056
TI  - Interindividual variability in catalytic activity and immunoreactivity of three
      major human liver cytochrome P450 isozymes.
AB  - OBJECTIVE: Interindividual variations in immunoreactivity and function of three
      major human drug metabolising P450 monooxygenases has been investigated in liver
      microsomes from 42 Caucasians (kidney donors or liver biopsies). METHODS:
      Diclofenac 4'-hydroxylation, dextromethorphan O-demethylation and midazolam 1'
      hydroxylation, measured by HPLC in incubates, were used as probes to determine
      CYP2C9, CYP2D6 and CYP3A4 function kinetics, respectively. Immunoquantification
      of the three isoforms was achieved by Western blotting, using rabbit polyclonal
      antibodies raised against human CYP2C9 and human CYP3A4, and mouse monoclonal
      antibody raised against human CYP2D6. RESULTS: Diclofenac 4'-hydroxylation
      exhibited Michaelis-Menten kinetics with kM = 3.4 mumol.l-1 and Vmax = 45
      nmole.mg-1 P.h-1. Relative immunoreactivity of CYP2C9 was correlated with Vmax
      and CL(int). Dextromethorphan O-demethylation in EM (extensive metabolisers)
      liver microsomes also showed Michaelis-Menten kinetics, with kM = 4.4 mumol.l-1
      and Vmax = 5.0 nmol.mg-1 P.h-1. Relative immunoreactivity of CYP2D6 was
      correlated with Vmax and CL(int). Midazolam 1'-hydroxylation also exhibited
      Michaelis-Menten kinetics with kM = 3.3 mumol.l-1 and Vmax = 35 nmol.mg-1 P.h-1.
      Relative immunoreactivity of CYP3A4 was correlated with Vmax and CL(int).
      Immunoreactivity and function were correlated for each isozyme, but there was no
      cross correlation between isozymes. CONCLUSION: The velocity of metabolite
      formation (Vmax) by the three major human drug metabolising P450 monoxygenases is
      correlated with their immunoreactivity in liver microsomes. Interindividual
      variation was much larger for Vmax than kM. Interindividual variability was more
      pronounced for CYP2D6, probably due to the presence of several different
      functional alleles in the population of extensive metabolisers.

PMID- 8880057
TI  - Effect of the lipase inhibitor orlistat on the pharmacokinetics of four different
      antihypertensive drugs in healthy volunteers.
AB  - OBJECTIVE: To study the influence of the lipase inhibitor orlistat on the
      pharmacokinetics of the antihypertensive drugs atenolol, furosemide, captopril
      and nifedipine. METHODS: Four open-label, crossover studies were performed on six
      to eight healthy male volunteers. Orlistat was given in doses of 50 mg 3 times
      daily mid-meal for 7 (nifedipine and captopril) or 8 days (atenolol and
      furosemide). The four antihypertensive drugs (atenolol 100-mg tablet, furosemide
      40-mg tablet, captopril 50-mg tablet and nifedipine 20-mg slow-release tablet)
      were administered in single doses twice, once before and once together, with
      orlistat at the end of the orlistat treatment period. RESULTS: The plasma
      concentration time profiles and the pharmacokinetic parameters estimated for
      these drugs were in the expected range, except for furosemide, whose
      bioavailability was lower than reported in the literature. This was probably due
      to the fact that furosemide was given during a meal. There were minor, but
      statistically significant, differences in one of the pharmacokinetic parameters
      of furosemide and nifedipine (no difference for captopril and atenolol) when
      these drugs were given alone and in combination with orlistat: the half-life of
      furosemide was slightly longer, the time to peak plasma concentrations of
      nifedipine was slightly longer. None of these are considered to be clinically
      significant changes. CONCLUSIONS: The lipase inhibitor orlistat given 50 mg 3
      times daily does not alter the pharmacokinetics of atenolol, furosemide,
      nifedipine and captopril to a clinically significant extent.

PMID- 8880058
TI  - Evaluation of plasma and urinary salbutamol levels in COPD.
AB  - OBJECTIVE: To evaluate the use of trough plasma salbutamol and overnight urinary
      salbutamol excretion in the assessment of nebulised salbutamol delivery in
      patients with chronic obstructive pulmonary disease (COPD). METHODS: Twenty in
      patients with COPD receiving nebulised salbutamol, age 69.7 years, FEV1 38.1%
      predicted, were studied on two consecutive days, receiving four 2.5 mg doses of
      nebulised salbutamol on day 1 and four 5 mg doses of nebulised salbutamol on day
      2, the first dose at 8.00 h the last dose at 22.00 h. Salbutamol delivery was
      assessed after the last dose by trough plasma salbutamol 8.00 h and overnight
      urinary excretion of salbutamol (22.00-8.00 h). RESULTS: Levels of urinary
      salbutamol were detectable in all 20 patients at both doses, whereas for plasma
      salbutamol detectable levels were only found in 16/20 cases at the 2.5 mg dose
      and in all cases at the 5 mg dose. For overnight urinary salbutamol (microgram x
      10 h-1 n = 20) the results were 141 for 2.5 mg and 249 for 5 mg. The dose ratio
      for urinary salbutamol between 2.5 mg and 5 mg doses was 1.83. Results for plasma
      salbutamol (ng/ml, n = 16) were 1.58 at 2.5 mg and 2.43 at 5 mg: dose ratio
      (geometric mean) 1.49. CONCLUSION: Overnight urinary salbutamol provides a simple
      and effective measure of nebulised salbutamol delivery in patients with COPD,
      which would be suitable for studying nebuliser performance and compliance.

PMID- 8880059
TI  - Effect of ranitidine on renal clearance of lomefloxacin.
AB  - OBJECTIVE: To examine the effect of ranitidine on the renal clearance of
      lomefloxacin. SETTING: Department of Clinical Pharmacology, Jichi Medical School.
      METHODS: Lomefloxacin 200 mg and ranitidine 300 mg or its placebo were given
      orally in a randomised, double-blind, crossover design. Blood and urine samples
      were obtained during a 24-h period after dosing. RESULTS: The area under the
      plasma concentration-time curve and the elimination half-life of lomefloxacin
      were significantly increased following coadministration with ranitidine. These
      effects were caused by significant decreases in total (7.8%) and renal (22%)
      clearance of lomefloxacin. In contrast, creatinine clearance and urinary
      excretion of electrolytes were not influenced by ranitidine. CONCLUSION: As
      lomefloxacin and ranitidine are excreted in urine by renal tubular secretion, the
      present results suggest that the renal tubular secretion of lomefloxacin is
      diminished by ranitidine. As the reduction in lomefloxacin clearance is only
      marginal, it is probable that the drug interaction observed in this study is not
      of clinical significance.

PMID- 8880060
TI  - Inhibition by a putative antipsychotic quinolinone derivative (OPC-14597) of
      dopaminergic neurons in the ventral tegmental area.
AB  - The effects of the newly synthesized quinolinone derivative, OPC-14597 (7-{4-[4
      (2,3-dichlorophenyl)-1-piperazinyl]butyloxy}-3, 4-dihydro-2(1 H)-quinolinone), on
      dopaminergic neuronal activity in the ventral tegmental area were examined using
      both in vivo microiontophoretic methods in chloral hydrate-anesthetized rats and
      the tight-seal whole-cell patch-clamp technique in thin-slice preparations of the
      rat brain. Neurons in the ventral tegmental area were classified as type I or
      type II according to their responses to antidromic stimulation of the nucleus
      accumbens, probably corresponding to dopaminergic and non-dopaminergic neurons,
      respectively. Antidromic spikes elicited by nucleus accumbens stimulation were
      inhibited by microiontophoretic application of dopamine and OPC-14597 in type I,
      but not in type II neurons. Although the OPC-14597-induced inhibition was
      antagonized by simultaneous application of domperidone (5-chloro-1-[1-[3-(2,3
      dihydro-2-oxo-1 H-benzimidazo-1-yl)-propy]-4-piperidinyl]-1,3-dihydro-2H-
      benzimidazol-2-one; dopamine D2 receptor antagonist), SCH 23390 (R(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1 H-3-benzazepine hydrochloride;
      dopamine D1 receptor antagonist) had no such effect. Spontaneous firing of type I
      neurons was also inhibited by iontophoretically applied OPC-14597 and dopamine,
      whereas that of type II neurons was unaffected. The inhibitory effect of OPC
      14597 on the spontaneous firing of type I neurons was antagonized by domperidone,
      but not by SCH 23390. In a whole-cell patch-clamp study using a thin-slice
      preparation of the rat brain, bath application of OPC-14597 induced
      hyperpolarization accompanied by inhibition of spontaneously occurring action
      potentials in the large neurons (> 20 microns in diameter) in a concentration
      dependent manner. These results suggest that OPC-14597 acts on dopaminergic
      neurons in the ventral tegmental area as a dopamine D2 receptor agonist to
      inhibit neuronal activities, probably by increasing membrane potassium
      conductance.

PMID- 8880061
TI  - Dibenzoazepine analogues: the electrophysiological properties of JL3, a potential
      atypical antidepressant.
AB  - JL3, 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine, has potent
      antidepressant-like activity in Porsolt's test in mice. Therefore, its influence
      on the electrical activity of central monoaminergic neurons was investigated in
      rats anaesthetized with chloral hydrate. JL3 induced a marked decrease of the
      firing rate of dorsal raphe serotonergic neurons (ID50 = 3.87 +/- 0.57 mg kg-1)
      and of locus coeruleus noradrenergic neurons (ID50 = 2.63 +/- 0.35 mg kg-1). The
      drug did not modify the electrical activity of A10 dopaminergic neurons. JL3 does
      not block amine uptake but it has affinity for 5-HT1A and 5-HT2 receptors. It is
      speculated that serotonergic mechanisms could play a role in the
      electrophysiological effects of JL3.

PMID- 8880062
TI  - Thermodynamics of the interaction of d-tubocurarine with nicotinic receptors of
      mammalian skeletal muscle in vitro.
AB  - Thermodynamic study is important for defining drug receptor interactions, and
      denervated rat hemidiaphragm is a unique preparation for such a study on
      nicotinic receptors. As a continuation of our earlier study with
      acetylthiocholine on the same preparation, we now report on the characteristics
      of temperature-dependent binding of d-tubocurarine, a reversible antagonist. The
      O. Arunlakshana and H.O. Schild (1959, Br. J. Pharmacol. 14, 48) equation, as
      improved by D.R. Woud and R.B. Parker (1971, J. Pharmacol. Exp. Ther. 177, 13),
      was used to calculate the dissociation constant of d-tubocurarine at various
      temperatures (10-37 degrees C) from the parallel shift of the acetylcholine dose
      response curve to the right by effective doses of d-tubocurarine. It was observed
      that the values of the dissociation constant increased with a decrease in
      temperature. Both the enthalpy (delta H degree) and entropy (delta S degree)
      changes as evaluated from the van't Hoff plot (In Kd vs. 1/T) were found to be
      positive and their relative value (delta H degree - T delta S degree) produced a
      negative free energy change which characterises the binding of d-tubocurarine as
      an entropy-controlled process. This finding is in agreement with the neurotoxin
      binding reported earlier. The present finding and earlier observations with
      acetylthiocholine reveal that agonist and antagonist binding to the nicotinic
      receptor may differ depending on the experimental conditions.

PMID- 8880063
TI  - Long-term plasticity in cingulate cortex requires both NMDA and metabotropic
      glutamate receptor activation.
AB  - We tested whether induction of homosynaptic long-term potentiation and long-term
      depression of synaptic strength in posterior cingulate cortex requires NMDA
      and/or metabotropic glutamate (mGlu) receptor activation. In in-vitro slices of
      rat posterior cingulate cortex, the NMDA receptor antagonist D-2-amino-5
      phosphonopentanoic acid (D-AP5; 15-20 microM) blocked induction of both long-term
      potentiation and long-term depression of mono- and polysynaptic population
      potentials in deep laminae. In contrast, DL-2-amino-3-phosphonopropionic acid (DL
      AP3; 15-25 microM), a selective mGlu receptor antagonist, blocked homosynaptic
      long-term potentiation and long-term depression of monosynaptic transmission, but
      was ineffective in blocking the induction of either type of plasticity at
      polysynaptically-driven sites. The selective mGlu receptor agonist, trans-1
      aminocyclopentane-1,3-dicarboxylic acid (ACPD), induced a marked depression of
      subicular-evoked monosynaptic potentials which reversed upon drug washout, but
      produced little depression of polysynaptic responses. We conclude that
      metabotropic glutamate receptor activation is necessary for the induction of long
      term synaptic plasticity only at monosynaptic subiculo-cingulate terminals, while
      NMDA receptor activation is necessary for the induction of long-term
      potentiation/long-term depression of both mono- and polysynaptic pathways.

PMID- 8880064
TI  - Rate-dependent effects of ajmaline and propafenone on atrioventricular
      conduction.
AB  - The aim of the present study was to characterize the time dependence of the
      depressant effects of ajmaline and propafenone on the Ca(2+)-channel-dependent
      tissue of the atrioventricular node in isolated guinea pig hearts perfused by the
      method of Langendorff. Ajmaline at a concentration of 0.03 microM and propafenone
      at a concentration of 0.3 microM caused a significant and comparable prolongation
      of the His bundle and atrioventricular conduction time (AVCT). When the pacing
      cycle length was abruptly shortened from 240 to 180 ms, the mean time constant
      (tau on) of the rate-dependent AVCT prolongation was comparable for ajmaline and
      propafenone. In contrast, if the pacing cycle length was abruptly increased from
      180 to 240 ms the mean time constant (tau off) for ajmaline was significantly
      higher than for propafenone. The rate-dependent increase of the atrioventricular
      effective refractory period was significantly more pronounced in the presence of
      ajmaline than of propafenone. Ajmaline and propafenone affect the Ca(2+)-channel
      dependent tissue of the myocardium. The more pronounced rate-dependent effect of
      ajmaline on the atrioventricular effective refractory period may be explained by
      a slower dissociation kinetic from the channel.

PMID- 8880065
TI  - A water-soluble, stable dipeptide NK1 receptor-selective neurokinin receptor
      antagonist with potent in vivo pharmacological effects: S18523.
AB  - The potassium salt of a chemically stabilized dipeptide, {1-[4-(1 H-tetrazol-5
      yl)butyl]indol-3-yl}carbonyl-Hyp-Nal-N(methyl)-Bzl , (Hyp = (R)-4-hydroxy-L
      proline; Nal = 3-L-(beta-naphthyl)-alanine), S18523, is described as a new water
      soluble, potent and selective NK1 receptor antagonist. The low molecular weight
      antagonist (M(r) = 736) displays nanomolar potency (pA2 = 9.6) in the rabbit vena
      cava (NK1) bioassay and nanomolar affinity (pKi = 9.1) on the human NK1 receptor
      expressed by lymphoblastoma cells. It is devoid of mu-opiate affinity (Ki > 10(
      4) M with respect to tritiated Tyr-DAla-Gly-MePhe-Gly-ol), has negligible calcium
      channel affinity (estimated Ki = 2.6 x 10(-5) M, with respect to isradipine) and
      does not cause peritoneal mast-cell degranulation. S18523 has strong
      antinociceptive effects in three classical pain tests in vivo both by i.v. and
      p.o. routes. The dipeptide potently antagonizes bronchoconstriction provoked by
      exogenous substance P in the guinea-pig and acts longer than the non-peptide
      antagonist CP99994, when administered as aerosol. Finally, S18523 displays
      antiinflammatory properties, since it dose-dependently inhibits substance P
      induced plasma extravasation both in the bladder (ID50 = 0.18 mg/kg i.v.) and
      bronchi (ID50 = 0.14 mg/kg i.v.) of the guinea-pig.

PMID- 8880066
TI  - Quantitative autoradiography of peripheral opioid binding sites in rat lung.
AB  - Previous studies in our laboratory have characterized non-conventional opioid
      binding sites in membrane preparations from both rat and human lung. The studies
      described in this paper utilized autoradiography to investigate the regional
      distribution of these [3H]morphine binding sites within rat lungs. Specific
      binding of [3H]morphine was saturable and Rosenthal analysis of tissue section
      wipes revealed the presence of both high-affinity and low-affinity opioid binding
      sites. The mean +/- S.E.M. binding affinity and the mean +/- S.E.M. density
      values for the low-affinity binding site (Kd = 217 +/- 160 nM, Bmax = 12 +/- 8
      pmol/mg protein) were similar to the values obtained in our previous whole-rat
      lung membrane binding assays (Kd = 187 +/- 36 nM, Bmax = 13.5 +/- 2 pmol/mg
      protein) (Cabot, P.J., P.R. Dodd, T. Cramond and M.T. Smith, 1994, Eur. J.
      Pharmacol. 268, 247). Quantitative autoradiography showed that the highest
      density of opioid binding sites appeared to be present within the alveolar wall
      (13.2 +/- 0.8 pmol/mg protein). A significantly lower (P < 0.05) density of
      binding was also observed in the smooth muscle of the trachea and main bronchi
      (5.5 +/- 2.1 pmol/mg protein). However, no morphine binding sites were evident in
      the smooth muscle surrounding the smaller airways and pulmonary vasculature
      within the lobes of the rat lung. It remains to be investigated whether the
      opioid binding sites located within the trachea and main bronchi of the rat
      airways are the prejunctional opioid receptors on C-afferent nerve fibres which
      modulate the release of potent inflammatory neuropeptides.

PMID- 8880067
TI  - Selective inhibition of neuropeptide Y Y1 receptors by BIBP3226 in rat and human
      epithelial preparations.
AB  - BIBP3226 (N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-D-arginine amide) has
      been used to examine the presence of neuropeptide Y Y1 receptors in 3
      gastrointestinal epithelial preparations, namely the rat jejunum and descending
      colon mucosae and a human colonic adenocarcinoma cell line. The selective Y1
      receptor antagonist (1 microM BIBP3226) had no significant effect upon either
      peptide YY (PYY) responses or on electric field stimulated changes in
      electrogenic ion transport in rat jejunum mucosa. Partial inhibition of PYY
      responses was observed following BIBP3226 pretreatment of rat colon mucosal
      preparations in the presence and absence of tetrodotoxin. Responses to the Y1
      selective agonist [Leu31,Pro34]neuropeptide Y ([Leu31, Pro34]NPY) in descending
      colon preparations were significantly attenuated by BIBP3226 (1 microM). The same
      concentration of antagonist abolished responses to PYY and [Leu31,Pro34]NPY but
      had no effect upon human pancreatic polypeptide (hPP) in monolayer cultures of
      the human adenocarcinoma cell line, Colony-6. Schild analysis of BIBP3226
      antagonism of PYY responses in Colony-6 cells provided a pA2 value of 7.9 with a
      Hill slope of 1.03, indicating competitive antagonism at these epithelial Y1
      receptors.

PMID- 8880068
TI  - Activation of group III metabotropic glutamate receptors is neuroprotective in
      cortical cultures.
AB  - (RS)-alpha-Methyl-4-phosphonophenylglycine (MPPG) and (S)-alpha-methyl-3
      carboxyphenylalanine (M3CPA), two novel preferential antagonists of group III
      metabotropic glutamate (mGlu) receptors, antagonized the neuroprotective activity
      of L-2-amino-4-phosphono-butanoate (L-AP4) or L-serine-O-phosphate in mice
      cultured cortical cells exposed to a toxic pulse of N-methyl-D-aspartate. In
      contrast, MPPG did not influence the neuroprotective activity of the selective
      group II mGlu receptor agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxy-cyclopropyl)
      glycine (DCG-IV). These results indicate that activation of group III mGu
      receptors exerts neuroprotective activity against excitotoxic neuronal death. At
      least one of the two major group III mGlu receptor subtypes, i.e. mGlu4 receptor,
      is expressed by cultured cortical neurons, as shown by immunocytochemical
      analysis with specific polyclonal antibodies.

PMID- 8880069
TI  - Endothelin-3, Ca2+ mobilization and cyclic GMP content in human platelets.
AB  - As previously described for endothelin-3, platelet exposure to cyclic GMP
      elevating agents such as sodium nitroprusside and M&B-22948 (2-o-propoxyphenyl-8
      azapurin-6-one), a cGMP phosphodiesterase inhibitor, lowered Ca2+ mobilization in
      response to thrombin. Interestingly, when cGMP phosphodiesterases were blocked,
      endothelin-3 produced a dose-dependent cGMP accumulation (P < 0.001). Since
      endothelin-3 has been proposed to decrease the activity of Ca2+ accumulating
      pumps, we examined whether this latter effect could be mediated by a rise in cGMP
      content. Cyclic GMP decreased in a dose-dependent manner the initial rate and
      plateau value of the ATP-dependent 45Ca2+ uptake in platelet membrane vesicles (P
      = 0.006 for each). Furthermore, combined treatment with endothelin-3 and M&B
      22948 or a moderate concentration of Na(+)-nitroprusside further reduced the
      thrombin-evoked Ca2+ discharge (P = 0.004 and 0.01, respectively), suggesting
      that endothelin-3 pre-exposure had reduced the amount of mobilizable Ca2+. We
      propose that the depletion of platelet Ca2+ stores and the reduction of Ca2+
      release evoked by endothelin-3 could be due, at least in part, to the elevation
      of cGMP content and to a decrease in Ca2+ accumulating pump activity.

PMID- 8880071
TI  - Alpha 2-adrenoceptor subtypes in the human brain: a pharmacological delineation
      of [3H]RX-821002 binding to membranes and tissue sections.
AB  - In order to study the characterization and localization of [3H]RX-821002 (2
      methoxy-idazoxan) binding to alpha 2-adrenoceptor subtypes in several regions of
      the human brain, we have carried out competition studies using both
      autoradiography and membrane binding assays. The alpha 2A-adrenoceptor subtype
      was found to be predominant in the different layers of the frontal cortex,
      cerebellum and hippocampal formation, while in the neostriatum it was the non
      alpha 2A- (alpha 2B- and alpha 2C-) adrenoceptor subtype. In the frontal cortex,
      in addition to binding to the alpha 2A-adrenoceptor subtype, [3H]RX-821002 bound
      also to a small portion of alpha 2B- and alpha 2C-adrenoceptors in layer III, and
      to an unidentified binding site in the external layers. In the hippocampus, both
      alpha 2A- and non-alpha 2A- (alpha 2B- and alpha 2C-) adrenoceptors were labelled
      in the dentate gyrus and the CA1 field, together with 5-HT1A receptors. 5-HT1A
      receptors were labelled predominantly in the stratum pyramidale layer. These
      results, in addition to delineate the relative presence of alpha 2-adrenoceptor
      subtypes, indicate that caution is needed when analyzing RX 821002 binding to
      human brain tissue.

PMID- 8880070
TI  - Modulation of intercellular communication between smooth muscle cells by growth
      factors and cytokines.
AB  - We recently reported that tumor necrosis factor alpha is able to cause a dose
      dependent and persistent reduction in gap junctional intercellular communication
      between primary human smooth muscle cells. In order to study whether this
      observed persistent reduction in gap junctional intercellular communication is a
      unique feature for tumor necrosis factor alpha, the present study focuses on the
      effects of other growth factors and cytokines on gap junctional intercellular
      communication. Platelet-derived growth factor AA and BB (PDGF-AA, PDGF-BB), basic
      fibroblast growth factor (bFGF), interleukin-6 and interferon-gamma were able to
      modulate gap junctional intercellular communication between primary human smooth
      muscle cells in vitro. However, our results demonstrate that the magnitude and
      nature of the observed effects are growth factor- and cytokine-specific. PDGF-AA,
      PDGF-BB and interleukin-6 caused a transient reduction in gap junctional
      intercellular communication, while bFGF induced a transient increase in gap
      junctional intercellular communication. Interferon-gamma was shown to be capable
      of causing a persistent reduction in gap junctional intercellular communication.
      In addition, PDGF-AA, PDGF-BB, bFGF, interleukin-6, interferon-gamma and tumor
      necrosis factor alpha all stimulated smooth muscle cell proliferation. These
      observations suggest a more complex relationship between modulation of gap
      junctional intercellular communication and cell proliferation than current
      hypotheses imply. The implications of the observed effects of growth factors and
      cytokines on gap junctional intercellular communication between smooth muscle
      cells in relation to the process of atherosclerosis is discussed.

PMID- 8880072
TI  - Ptilomycalin A, a novel Na+, K(+)- or Ca2(+)-ATPase inhibitor, competitively
      interacts with ATP at its binding site.
AB  - Ptilomycalin A inhibited the brain Na+, K(+)-ATPase and Ca2(+)-ATPase from
      skeletal sarcoplasmic reticulum with an IC50 value of 2 microM and 10 microM,
      respectively. Kinetic analysis of the inhibitory effects of ptilomycalin A
      suggests that the inhibition of Na+, K(+)-ATPase is a competitive-, an
      uncompetitive- and an anticompetitive-type with respect to ATP, Na+ and K+,
      respectively. The inhibition of Ca2(+)-ATPase by ptilomycalin A is a competitive-
      or an uncompetitive-type with respect to ATP or Ca2+, respectively. These results
      suggest that ptilomycalin A interacts with ATP at the ATP binding site of Na+,
      K(+)-ATPase or Ca2(+)-ATPase. Ptilomycalin A has become a useful biochemical tool
      for clarifying the ATP binding site in both enzymes.

PMID- 8880073
TI  - Behavioural and immunological effects of the antihistamine terfenadine in
      olfactory bulbectomized rats.
AB  - The effects of chronic treatment with the non-sedative histamine H1 receptor
      antagonist terfenadine (5 mg/kg, i.p.) for 16 days on some behavioural and
      immunological parameters were studied in the olfactory bulbectomized (OB) rat
      model of depression. In the open field apparatus, OB rats showed a significant
      increase in ambulation and rearing scores. Following terfenadine treatment, this
      hyperactivity was significantly attenuated. In untreated OB rats, neutrophils
      phagocytosis and lymphocyte proliferation were significantly suppressed.
      Terfenadine administration markedly reversed the suppression of these
      immunological parameters in the treated OB animals, but did not reverse the
      abnormalities in the differential white blood cell count caused by bulbectomy.
      These results suggest that the histamine H1 receptor antagonist terfenadine may
      have antidepressant properties and that terfenadine is effective in reversing
      some of behavioural and immune changes in the olfactory bulbectomized rat model
      of depression.

PMID- 8880074
TI  - Acute, subchronic and discontinuation effects of zopiclone on sleep EEG and
      nocturnal melatonin secretion.
AB  - Zopiclone is a new short half-life cyclopyrrolone hypnotic agent acting at the
      GABA-benzodiazepine receptor complex. In order to characterize its
      pharmacological profile, the effects of 7.5 mg zopiclone on nocturnal melatonin
      secretion were investigated under polysomnographic control in 11 healthy subjects
      following acute and subchronic administration as well as after abrupt
      discontinuation of the drug. No effect of zopiclone on the melatonin plasma
      levels could be observed. Regarding both total melatonin production and the
      temporal pattern of melatonin secretion during the night, there was no difference
      between placebo baseline condition, acute and subchronic administration, and
      discontinuation. In contrast, the sleep EEG data demonstrated the hypnotic
      efficacy of zopiclone under acute administration and indicated a rebound insomnia
      after abrupt discontinuation. Moreover, alterations of sleep architecture were
      found under treatment as well as after discontinuation. Whereas, with regard to
      sleep EEG parameters, zopiclone appears to be comparable with some short-acting
      benzodiazepines, a discrepancy between the missing effect of zopiclone on pineal
      function and the suppressing influence of benzodiazepines known from the
      literature becomes obvious. The fact that zopiclone does not interfere with
      nocturnal melatonin secretion at pharmacologically active doses as indicated by
      alterations in sleep EEG parameters might possibly point to a pharmacodynamic
      difference between the two drug classes.

PMID- 8880075
TI  - 5HT2C receptor agonists exhibit antidepressant-like properties in the anhedonia
      model of depression in rats.
AB  - Potential antidepressant properties of preferential 5HT2C receptor agonists were
      investigated in stress-induced anhedonia, a validated simulation of depression.
      This simulation evaluates the hedonic state of stressed rats by recording
      variations in self-stimulation threshold measured before, during, and after
      exposure to intermittent, unpredictable, mild stressors. This stress regimen
      gradually elevates self-stimulation threshold, suggesting the development of an
      anhedonic state. In stressed animals, chronic treatment with the preferential
      5HT2C receptor agonists Ro 60-0175 and Ro 60-0332 (3 mg/kg i.p. b.i.d.) prevented
      the loss of sensitivity to reward. Similarly, when stressed anhedonic animals
      were curatively treated with Ro 60-0175 (3 mg/kg i.p. b.i.d.), the stress-induced
      anhedonia was gradually reversed. These results suggest a role for 5HT2C
      receptors in some aspects of depression, and potential antidepressant properties
      for selective 5HT2C receptor agonists. Such compounds may offer an innovative
      approach to the treatment of mood disorders.

PMID- 8880076
TI  - The effects of moclobemide on sexual desire and function in healthy volunteers.
AB  - Decreased sexual desire is a recognized symptom of major depression (MD).
      Disturbances in sexual function, although reported in drug = free patients, have
      more often been viewed as adverse drug effects during antidepressant treatment
      with established classes of antidepressants (TCA, MAOI, SSRI). However, it is
      difficult to draw conclusions about the effects of antidepressants on sexual
      desire and function for two reasons: lack of standardised assessments for sexual
      function; inability to distinguish depression-related symptoms from drug-induced
      sexual disturbances. The purpose of this study was to examine the effects of
      moclobemide (a RIMA antidepressant) on sexual function in healthy male and female
      volunteers. Sixty male and female volunteers were randomly assigned to either
      moclobemide 300 mg or placebo for 3 weeks. They were seen at weekly intervals to
      assess drug compliance and to complete a 10-item sexual function questionnaire
      (SFQ). In both men and women there were no differences between moclobemide and
      placebo on measures of sexual desire and function. However, men and women
      differed in the levels of reported interest and sexual performance.

PMID- 8880077
TI  - Intracerebroventricular La3+ but not Gd3+ inhibits cocaine-induced motor
      activation in rats.
AB  - In the present work the effects of i.c.v. administration of La3+ and Gd3+ on the
      motor stimulant effect of cocaine in rats were studied. Both La3+ and Gd3+ failed
      to influence basal motor activity. However, the two metal ions differ in
      modulation of cocaine-induced activation of motor activity. While Gd3+ (10.0,
      20.0 and 40.0 mM/1 ml) did not influence significantly the cocaine effect, La3+
      (0.1, 1.0 and 10 mM/1 ml) inhibited cocaine-induced motor activation in a dose
      dependent manner. The results suggest the possible involvement of La(3+)-but not
      Gd(3+)-sensitive calcium channels in the locomotor stimulant effect of cocaine.

PMID- 8880078
TI  - The panic-inducing properties of the cholecystokinin tetrapeptide CCK4 in
      patients with panic disorder.
AB  - We studied the effect of the cholecystokinin tetrapeptide (CCK4), a potent CCKB
      antagonist, in patients with panic disorder. Two different dosages (25 and 50
      micrograms) of CCK4 and saline were tested in 12 patients who were randomly
      allocated to 2 of the 3 possible treatment groups. Patients were tested on 2
      separate occasions, 1 week apart, using an unbalanced single-blind incomplete
      block design. A total of 24 intravenous injections were carried out. The panic
      rate with 25 micrograms CCK was 44% (4/9) and 71% (5/7) with 50 micrograms. None
      of the patients panicked with saline (0/8). Patients' symptom responses were very
      similar to their spontaneous panic attacks. Taking the Panic Symptom Scale (PSS)
      as outcome variable, we found that CCK4 provoked symptoms of panic in a dose
      dependent fashion. The behavioral response to CCK4 was not accompanied by
      activation of the hypothalamic-pituitary-adrenal (HPA) axis as measured by the
      prolactin and cortisol responses. Moreover, CCK4-induced panic symptoms were not
      correlated with plasma increases in the principal noradrenergic metabolite, 3
      methoxy-4-hydroxy-phenylglycol (MHPG), suggesting that activation of the locus
      coeruleus may not be critical for CCK4-induced panic.

PMID- 8880079
TI  - Impairment of the blood-CSF barrier in suicide attempters.
AB  - In a patient group of 90 suicide attempters, 18% showed an impaired blood-CSF
      barrier; of these 16 patients, all but one were younger than 45 years. When
      compared with 105 healthy controls, a significant difference in impairment of the
      blood-CSF barrier, between patients and controls, was seen only in those younger
      than 45 years (z = -2.66; P < 0.01). Paracetamol intoxication was more common
      among those with an impaired blood-CSF barrier than among those without an
      impairment (Fisher's exact test, P = 0.00029). Paracetamol intoxication was the
      most common method of suicide attempt in patients with adjustment disorders.
      There was no significant association between alcohol and/or drug abuse and an
      impaired blood-CSF barrier (Fisher's exact test, P = 0.91977). There were no
      differences in IgG index between patients and controls. The hypothesis that a
      blood-CSF barrier leakage may be a confounding factor when assessing the levels
      of monoamine metabolites in the CSF did not receive any support.

PMID- 8880080
TI  - Strain differences in mice antinociception: relationship between alprazolam and
      opioid receptor subtypes.
AB  - This study was designed to investigate the antinociceptive effects of one of the
      most prescribed benzodiazepines (BZ) -i.e., alprazolam. Groups of CD-1, SWISS,
      BALB/c and C57BL mice were treated with alprazolam. Analgesia was assayed, using
      the radiant heat tailflick assay. Alprazolam given i.p. elicited analgesia in a
      dose-dependent manner only in the BALB/c mice (ED50 1.1 mg/kg). No analgesia was
      observed in CD-1 or C57BL mice. The sensitivity of SWISS mice was intermediate,
      but still very low. Intrathecally administered alprazolam elicited analgesia in
      BALB/c, Swiss and CD-1 mice with ED50 values of 10, 22.8 and 34.6 micrograms,
      respectively. No analgesia was observed in C57BL mice. Intracerebroventricular
      injections did not induce analgesia in any of the strains. In other sets of
      experiments with BALB/c mice, we found a supra-additivity increase in analgesia
      when a subthreshold dose of alprazolam was given with morphine (mu-subtype
      agonist). This interaction was antagonized by naloxone and less so by flumazenil.
      No effect was found when alprazolam was co-administered with other specific
      opioid agonists (delta and kappa). Our results demonstrate that injections of
      alprazolam can produce analgesia in different genetic subjects and can modify
      morphine-induced antinociception. The fact that the interaction between morphine
      and alprazolam analgesia was sensitive to naloxone but less to flumazenil
      indicates that the analgesic effects of alprazolam are mediated primarily by an
      opioid mechanism of action but less by benzodiazepines.

PMID- 8880082
TI  - The role of cytochrome P450 2D6 in the metabolism of moclobemide.
AB  - The metabolic fate of moclobemide (Ro 11-1163), a new reversible and selective
      inhibitor of monoamine oxidase type A (MAO-A), has been assessed in a pilot study
      in 2 debrisoquine poor metabolizers (PM) and 4 extensive metabolizers (EM) after
      multiple oral dosings of moclobemide with and without co-medication of
      dextromethorphan. Absorption and disposition parameters were not different
      between PM and EM. Concurrent application of dextromethorphan, a selective
      substrate of CYP2D6, did not affect the pharmacokinetics of moclobemide. These
      results indicate that the cytochromal isoenzyme CYP2D6 does not play a major role
      in the metabolic degradation of moclobemide. Limited CYP2D6 activities because of
      a genetic defect or co-medications with CYP2D6 substrates should therefore not
      give rise to elevated moclobemide blood levels.

PMID- 8880081
TI  - Depression as a spreading neuronal adjustment disorder.
AB  - The outlines of a theory of the pathophysiology of depression are presented. The
      classic monoamine theory of depression as well as its more recent elaborations
      suggests that a deficit in monoamine neurotransmitters in the synaptic cleft is
      the primary cause of depression. We suggest that the primary defect emerges in
      the regulation of firing rates in brainstem monoaminergic neurons, which brings
      about a decrease in the tonic release of neurotransmitters in their projection
      areas, an increase in postsynaptic sensitivity and, concomitantly, exaggerated
      responses to acute increases in presynaptic firing rate and transmitter release.
      We propose that the initial defect involves, in particular, the noradrenergic
      innervation from the locus coeruleus, which in turn leads to dysregulation of 5
      HT-ergic and dopaminergic neurotransmission.

PMID- 8880083
TI  - Differential effects of clonidine, lithium and quinine in the forced swimming
      test in mice for antidepressants: possible roles of serotoninergic systems.
AB  - The forced swimming test (FST) is a behavioral test used to predict the efficacy
      of antidepressant (AD) treatments. In the present study, it was found that, when
      combined with clonidine, lithium or quinine, subactive doses of several types of
      ADs (tricyclics, 5-HT uptake inhibitors and atypical ADs) produced anti
      immobility effects in mice. Clonidine (0.06 mg/kg) was found to potentiate the AD
      like effects of all the drugs tested in the FST. More interesting is the
      additivity of gepirone with lithium (1 mEq/l), and ondansetron with quinine (0.5
      mg/kg). The results of the present study are in favour of the potentiation of AD
      activity by clonidine via 5-HT2 receptors, lithium through 5-HT1A receptors, and
      quinine through 5-HT3 receptors. Further studies to examine in detail which of
      these three 5-HT receptors or their subtypes is the most important in the actions
      of individual ADs are warranted.

PMID- 8880084
TI  - Induction of c-fos gene expression by the selective sigma receptor ligand EMD
      57445 in rat brain.
AB  - Based on animal studies it has been reasoned that ligands to sigma binding sites
      might be effective in the treatment of schizophrenic disorders and may also be
      used to investigate this largely elusive disorder on a molecular level.
      Expression patterns of c-fos in rat brain were studied following treatment with
      single doses of the sigma ligand EMD 57445 (0.3, 1, 3, 30 mg/kg s.c.). Specific c
      fos gene expression was detected at all concentrations tested in various cortical
      areas. The signals observed were dose-dependent with the highest intensities in
      the piriform cortex. Strong signals were also detected in hippocampal areas CA
      1,2,3 and the gyrus dentatus, as well as in the medial habenula nuclei. In the
      caudate putamen, nucleus accumbens and lateral septal nucleus signals were
      detectable after administration of doses > or = 1 mg/kg. Furthermore, c-fos
      hybridization was visible in the amygdala, in the mammillary bodies, the islands
      of Calleja and in the olfactory tubercle. In the hypothalamus, c-fos expression
      was seen in the median eminence area after 30 mg/kg EMD 57445. No hybridization
      signals were obtained in brainstem or cerebellum. Since c-fos expression induced
      by EMD 57445 resembled the pattern obtained with atypical neuroleptics and
      studies on animal behavior point to antipsychotic activity, it is concluded that
      the drug might be suitable in the treatment of schizophrenia.

PMID- 8880085
TI  - Lithium compared to valproic acid and carbamazepine in the treatment of mania: a
      statistical meta-analysis.
AB  - The hypothesis that lithium is the most appropriate and efficacious
      pharmacological treatment in the therapy of manic-depressive illness was examined
      in a meta-analysis. The efficacy of lithium was compared with that of the
      antiepileptics, carbamazepine and valproic acid. Data sources include the Medline
      database and relevant references from articles. Only randomised controlled
      clinical trials with a double-blind assessment of outcomes were included. Lithium
      levels were required to be within the therapeutic range of 0.4-1.5 mmol/l. The
      effect sizes were measured by the odds ratio using the Mantel-Haenszel method. No
      significant difference was observed between the treatment effect of the 3 drugs
      compared. While the efficacy of the 3 treatments was identical, there is a
      general tendency in favour of the antiepileptics in the treatment of manic
      depression with regard to adverse events and treatment tolerance. The impact and
      importance of this study seriously question the relevance of today's practice of
      prescribing lithium in the acute management of manic-depressive illness.

PMID- 8880086
TI  - Memory-enhancing effects of benzodiazepines in mice.
AB  - In the present study, post-trial effects of clonazepam and diazepam on inhibitory
      avoidance learning under two different experimental conditions (i.e., 0.25 or
      0.75 mA footshock) have been investigated. Both clonazepam (0.5 mg/kg) and
      diazepam (2 and 8 mg/kg) enhanced retention when administered immediately after
      the 0.25 mA footshock applied during training of the inhibitory avoidance task.
      In contrast, clonazepam and diazepam proved ineffective after the 0.75 mA
      footshock. The results suggest a post-training memory-enhancing effect of
      clonazepam and diazepam depending on the experimental conditions.

PMID- 8880087
TI  - Risperidone and reversible neutropenia: a negative rechallenge.
AB  - After 6 weeks of a risperidone rechallenge therapy (2-4 mg/day), no hematological
      abnormalities were observed in a 26-year-old schizophrenic woman. Two years
      previously after 9 days of risperidone therapy (2-6 mg/day), the same patient had
      developed a reversible neutropenia during a cold.

PMID- 8880088
TI  - Lung volume reduction surgery for emphysema: answers are beginning to accumulate.

PMID- 8880089
TI  - Management of spontaneous pneumothorax: back to the future.

PMID- 8880090
TI  - Classification of severe asthma exacerbations: a proposal.
AB  - The intensity of asthma exacerbations may vary from mild to severe. Many studies
      have demonstrated that the speed at which severe asthma exacerbation (SAE)
      develops varies among patients. In some asthmatics, the exacerbation comes on
      very quickly, whereas in others there is a progressive deterioration of clinical,
      functional and blood gas parameters. Sudden SAE are characterised by their
      explosive presentation and quick recovery. This evolution contrasts with that of
      patients with a slow onset SAE, who often need prolonged hospitalization. Absence
      of secretions suctioned from the airways during mechanical ventilation has been
      reported in sudden SAE, whereas large amounts of viscid mucus are found in
      patients with the slow onset SAE. The lungs of patients who died during a sudden
      onset SAE often show empty airways and a predominant neutrophilic infiltration in
      the bronchial epithelium, in contrast to the presence of abundant eosinophils in
      patients who died during a slow onset SAE. Sudden onset SAE may occur as sporadic
      cases or in outbreaks. Sporadic cases may result from the ingestion of
      nonsteroidal anti-inflammatory drugs (NSAID) in patients with intolerance to
      these products, massive exposure to common allergens and ingestion of foods
      containing sulphites. Asthma outbreaks have been described in many cities. In
      contrast to sudden onset SAE, slow onset SAE is characterized by a progressive
      deterioration, accompanied by an increase in the use of bronchodilators. Lack of
      appropriate monitoring of function by peak expiratory flow (PEF) recording,
      failure of patients to recognize worsening symptoms and underusage of inhaled and
      oral steroid treatment have been repeatedly identified as factors which are
      likely to be associated with slow onset SAE. The contribution of psychosocial
      problems, depression, denial of asthma severity and nonadherence with the
      treatment should not be overlooked in patients with slow onset SAE.
      Classification of severe asthma exacerbations into two types (sudden onset and
      slow onset) could help to reveal the aetiology of the attack and may also be
      relevant to the management of the patient.

PMID- 8880091
TI  - Effect of surgical lung volume reduction on respiratory muscle function in
      pulmonary emphysema.
AB  - Lung volume reduction surgery (LVRS) in patients with severe lung emphysema
      restores the thoracic configuration to a more normal functional capacity. The aim
      of this study was to investigate whether reduction in intrathoracic volume by
      LVRS improves the inspiratory muscle force generation of the respiratory pump.
      Pulmonary function tests, maximal inspiratory mouth pressure (MIP), sniff nasal
      inspiratory pressure (SNIP), sniff transdiaphragmatic pressure (Pdi), and
      inspiratory mouth occlusion pressure (P0.1) were measured in 17 emphysematous
      patients (mean (+/- SEM) age 53 +/- 2 yrs) before and 1 month after LVRS. The
      mean value of forced expiratory volume in one second (FEV1) increased (0.82 +/-
      0.07 vs 1.12 +/- 0.08 L; p < 0.0001), whilst there was a decrease (p < 0.0001) in
      residual volume (RV) (337 +/- 31 vs 250 +/- 21 % of predicted), functional
      residual capacity (FRC) (210 +/- 9 vs 159 +/- 9% pred), and total lung capacity
      (TLC) (138 +/- 6 vs 110 +/- 5% pred). The mean value of MIP increased by 52% from
      4.8 +/- 0.4 to 7.3 +/- 0.6 kPa (p < 0.001), the mean value of SNIP increased by
      66% from 3.9 +/- 0.4 to 6.5 +/- 0.5 kPa (p < 0.001), and the mean value of Pdi
      increased by 28% from 6.0 +/- 0.6 to 7.7 +/- 0.8 kPa (p < 0.05) after LVRS. P0.1
      decreased on average by 24% from 0.46 +/- 0.03 to 0.35 +/- 0.02 kPa after LVRS.
      No significant correlations were found between inspiratory muscle (MIP, SNIP,
      Pdi) and respiratory drive (P0.1) indices, lung function data, 6 min walk
      distance, or dyspnoea score. In conclusion, the observed clinical improvement of
      patients with severe emphysema after lung volume reduction surgery results, in
      part, from an increased ability of the inspiratory muscles to generate force,
      which is paralleled by a significant decrease in central respiratory drive.

PMID- 8880092
TI  - Physiological and morphological determinants of maximal expiratory flow in
      chronic obstructive lung disease.
AB  - Maximal expiratory flow in chronic obstructive pulmonary disease (COPD) could be
      reduced by three different mechanisms; loss of lung elastic recoil, decreased
      airway conductance upstream of flow-limiting segments; and increased
      collapsibility of airways. We hypothesized that decreased upstream conductance
      would be related to inflammation and thickening of the airway walls, increased
      collapsibility would be related to decreased airway cartilage volume, and
      decreased collapsibility to inflammation and thickening of the airway walls. Lung
      tissue was obtained from 72 patients with different degrees of COPD, who were
      operated upon for a solitary peripheral lung lesion. Maximal flow-static recoil
      (MFSR) plots to estimate upstream resistance and airway collapsibility were
      derived in 59 patients from preoperatively measured maximal expiratory flow
      volume and pressure-volume curves. In 341 transversely cut airway sections,
      airway size, airway wall dimensions and inflammatory changes were measured.
      Airflow obstruction correlated with lung elastic recoil and the MFSR estimate of
      airway conductance but not to airway collapsibility or to the amount of airway
      cartilage. The upstream conductance decreased as the inner wall became thicker.
      Airway collapsibility did not correlate with the amount of airway cartilage,
      inflammation, or airway wall thickness. We conclude that the maximal flow-static
      recoil model does not adequately reflect the collapsibility of the flow-limiting
      segment.

PMID- 8880093
TI  - Evaluation of an auto-nCPAP device based on snoring detection.
AB  - We evaluated an auto-nasal continuous positive airway pressure (nCPAP) prototype
      (MC+; SEFAM, Nancy, France) in which apnoea/hypopnoea detection was disabled and
      nasal mask pressure vibration detection was the only mode of pressure setting.
      The device was tested in 15 previously untreated obstructive sleep apnoea
      patients during a night with polysomnography. We observed that a single night of
      auto-nCPAP improved the apnoea/hypnoea index (AHI) (12 +/- 21 vs 51 +/- 31
      disordered breathing events.h-1 of sleep (mean +/- SD)), the awakening-arousal
      index (13 +/- 20 vs 40 +/- 26 arousals.h-1 of sleep), and duration of slow wave
      sleep (102 +/- 49 vs 71 +/- 56 min) but not of rapid eye movement (REM) sleep (55
      +/- 31 vs 64 +/- 38 min). Auto-nCPAP was effective (apnoea/hypopnoea and arousal
      indices < 10 events.h-1) in all but three patients. Auto-nCPAP was ineffective in
      one patient, whose obstructive respiratory events were not preceded by nasal mask
      pressure vibration detection, and in two patients who were quasi-permanent mouth
      breathers. Snoring detection may be effective in sleep apnoea syndrome with heavy
      snoring and without permanent mouth breathing, during the first night of nasal
      continuous positive airway pressure treatment.

PMID- 8880094
TI  - Relationship between body mass index, age and upper airway measurements in
      snorers and sleep apnoea patients.
AB  - Anatomical pharyngeal and craniofacial abnormalities have been reported using
      upper airway imaging in snorers with or without obstructive sleep apnoea (OSA).
      However, the influences of the age and weight of the patient on these
      abnormalities remain to be established. The aim of this study was, therefore, to
      evaluate in a large population of snorers with or without OSA, the relationship
      between body mass index (BMI), age and upper airway morphology. One hundred and
      forty patients were referred for assessment of a possible sleep-related breathing
      disorder and had complete polysomnography, cephalometry and upper airway computed
      tomography. For the whole population, OSA patients had more upper airway
      abnormalities than snorers. When subdivided for BMI and age, however, only lean
      or younger OSA patients were significantly different from snorers as regards
      their upper airway anatomy. The shape of the oropharynx and hypopharynx changed
      significantly with BMI both in OSA patients and snorers, being more spherical in
      the highest BMI group due mainly to a decrease in the transverse axis. On the
      other hand, older patients (> 63 yrs), whether snorers or apnoeics, had larger
      upper airways at all pharyngeal levels than the youngest group of patients (< 52
      yrs). For the total group of patients, upper airway variables explained 26% of
      the variance in apnoea/hypopnoea index (AHI), whereas in lean (BMI < 27 kg.m-2)
      or youngest (age < 52 yrs) subjects upper airway variables explained,
      respectively 69 and 55% of the variance in AHI. In conclusion, in lean or young
      subjects, upper airway abnormalities explain a major part of the variance in
      apnoea/hypopnoea index and are likely to play an important physiopathogenic role.
      This study also suggests that the shape of the pharyngeal lumen in awake subjects
      is more dependent on body mass index than on the presence of obstructive sleep
      apnoea. Further investigation looking at upper airway imaging for surgical
      selection in obstructive sleep apnoea should focus on lean and young patients.

PMID- 8880095
TI  - Respiratory challenge induces high frequency spiking on the static charge
      sensitive bed (SCSB).
AB  - The static charge sensitive bed (SCSB) is a simple and noninvasive device used
      for the detection of sleep apnoea. In addition to episodes of apnoea or
      hypopnoea, heavy snorers commonly present with episodes of high frequency spiking
      on the SCSB. These spiking episodes have been claimed to represent partial upper
      airway obstruction during sleep, but the mechanism of their appearance is not
      known. We studied the SCSB spiking phenomenon in awake subjects during
      experimental respiratory challenge. One female and five male volunteers were
      studied whilst breathing freely, during hypoxia, hypercapnia and inspiratory and
      expiratory loading. Oxygen saturation, end-tidal carbon dioxide tension, minute
      ventilation, oesophageal pressure, electrocardiographic activity (ECG), blood
      pressure and the SCSB signals were monitored. During free breathing, the SCSB
      high frequency signal consisted of low amplitude complexes with close time
      relationship to the cardiac cycle. During respiratory challenge, spiking
      occurred. These spikes showed no time relationship to the cardiac cycle, but were
      time-linked to the onset of inspiration or expiration. Spike amplitude correlated
      with breathing frequency (r2 = 0.59; p < 0.005) and variation in oesophageal
      pressure (r2 = 0.57; p < 0.005). We conclude that during quiet, unobstructed
      breathing the static charge sensitive bed high frequency signal represents
      cardiac activity (ballistocardiogram), whereas during high-drive breathing high
      frequency spikes are produced. These spikes are respiratory in origin and are
      likely to represent fast components of respiratory movements. Our results support
      the use of static charge sensitive bed spiking as a noninvasive measure of
      breathing stimulation.

PMID- 8880096
TI  - Benzodiazepine receptor antagonist (flumazenil) does not affect sleep-related
      breathing disorders.
AB  - Benzodiazepine drugs may impair breathing during sleep, leading to the
      development of sleep-disordered breathing or, in subjects with sleep apnoea, an
      increase in the severity of pre-existing apnoeas. Flumazenil is a selective
      benzodiazepine-antagonist. We hypothesized that endogenous ligands of
      benzodiazepine receptors might contribute to the pathogenesis of obstructive
      sleep apnoea syndrome (OSAS) and that the intensity of OSAS could, therefore, be
      reduced by flumazenil. Ten male patients (mean age 55 yrs, mean body mass index
      42.4 kg.m-2, mean apnoea index (AI) 53.5 and mean respiratory disturbance index
      (RDI) 74.2) were investigated. None of the patients had been treated for OSAS
      prior to the study. The study design was randomized, single-blind, placebo
      controlled and cross-over. On the first or second study night, patients were
      randomly assigned to receive i.v. flumazenil (2 mg) or placebo (0.9% NaCl)
      between 01:00 and 01:30 h. Comparing the polysomnographic results of the placebo
      night and the flumazenil night in all 10 patients, no significant differences
      were found regarding obstructive events or sleep architecture. Accordingly, the
      data concerning sleep-disordered breathing and sleep stages during the 30 min
      period prior to and the 30 min period following the administration of flumazenil
      did not differ. It is concluded that endogenous ligands of the benzodiazepine
      receptor play no role in the pathogenesis of obstructive sleep apnoea syndrome,
      since respiratory and sleep data are not altered by flumazenil. Therefore,
      attempts to treat obstructive sleep apnoea syndrome with flumazenil do not seem
      to be warranted.

PMID- 8880097
TI  - Cost-effectiveness of video-assisted thoracoscopic surgery versus conservative
      treatment for first time or recurrent spontaneous pneumothorax.
AB  - The aim of this study was to analyse differences in efficacy and costs in
      treating first time or recurrent spontaneous pneumothorax by conservative therapy
      (pleural drainage or observation) and video-assisted thoracoscopic surgery
      (VATS). Retrospectively, 112 patients treated by conservative therapy during 1985
      1989 (Period 1) were compared with 97 patients treated by VATS during 1991-1994
      (Period 2). Mean follow-up time in each period was more than 2 yrs. Patients in
      both periods had comparable clinical characteristics. Irrespective of first time
      or recurrent spontaneous pneumothorax at presentation, drainage and
      hospitalization times were longer, and complication and recurrence rates were
      higher in Period 1. When costs due to the waiting time before VATS were excluded,
      the total costs in Period 1 were higher than in Period 2. Video-assisted
      thoracoscopic surgery is more effective in treating patients with first time or
      recurrent spontaneous pneumothorax, with less morbidity and total costs compared
      to conservative therapy. In view of cost-effectiveness, we feel that a different
      management of first time or recurrent spontaneous pneumothorax is not justified.

PMID- 8880098
TI  - Prognostic significance of thrombocytosis in patients with primary lung cancer.
AB  - In patients with malignancies, thrombocytosis has previously been related to
      disease stage, histological type, and survival. In the present study, the
      prevalence of thrombocytosis and the prognostic information provided by platelet
      counts were analysed in a large cohort of patients with primary lung cancer. At
      the time of diagnosis, pretreatment platelet counts were retrospectively recorded
      in 1,115 consecutive patients with histologically proven primary lung cancer. All
      patients were reviewed regarding histological type, tumour, node, metastasis
      (TNM) classification stage and survival. The prevalence of thrombocytosis in
      patients with lung cancer was compared with that in a series of 550 consecutive
      out-patients with benign lung disorders. In 269 surgically resected patients,
      postoperative platelet counts were recorded 1-3 months after resection of the
      tumour. In the follow-up period, thromboembolic episodes diagnosed either
      clinically or at autopsy were recorded. The overall prevalence of thrombocytosis
      (> 400 x 10(9) platelets.L-1) in the patients with lung cancer was 32%. The
      frequency of thrombocytosis was significantly higher compared with the control
      subjects (32 vs 6%; p < 0.0001). Platelet counts differed significantly among
      subgroups defined by the TNM classification, with the proportion of patients with
      > 400 x 10(9) platelets.L-1 greatest in the more advanced TNM stages (stage I and
      II 23% vs stage III and IV 37%; p < 0.0001). Patients with thrombocytosis had a
      significantly poorer survival than patients with normal platelet counts (p <
      0.0001). In a multivariate survival analysis (Cox model), thrombocytosis
      continued to correlate strongly with poor survival even when adjusted for
      histological type, sex, age, and TNM stage (p < 0.001). In surgically resected
      patients, the frequency of preoperative and postoperative thrombocytosis differed
      significantly (23.0 vs 8.9%; p < 0.0001). Survival rate was significantly reduced
      in patients with preoperative thrombocytosis (p = 0.005). Thrombocytosis was not
      associated with an increased incidence of thromboembolism. In conclusion,
      thrombocytosis is an independent prognostic factor of survival in patients with
      primary lung cancer. We suggest that platelet counts should be included in future
      multivariate analyses of survival in patients with lung cancer.

PMID- 8880099
TI  - ICAM-1 expression by lung cancer cell lines: effects of upregulation by cytokines
      on the interaction with LAK cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1) expression by tumour cells may be
      involved in their interaction with defensive cells. In this study the surface
      ICAM-1 expression and soluble ICAM-1 (sICAM-1) production by five small cell lung
      cancer (SCLC) and five non-SCLC (NSCLC) cell lines was investigated. In addition,
      the effects of ICAM-1 upregulation by cytokines on the adhesion of lung cancer
      cells to allogeneic lymphokine-activated killer (LAK) cells and susceptibility to
      LAK cytotoxicity was also evaluated. ICAM-1 expression was assessed by flow
      cytometry. Soluble ICAM-1 release was measured by enzyme-linked immunosorbent
      assay (ELISA). Interaction with LAK cells was tested by adhesion and cytotoxicity
      assays. At baseline, SCLC lines did not express ICAM-1, while 4 of the 5 NSCLC
      lines expressed ICAM-1. ICAM-1 expression was induced by interferon-gamma (IFN
      gamma) in 4 of the 5 SCLC lines and upregulated in 1 of the 5 NSCLC lines. ICAM-1
      expression was induced by tumour necrosis factor-alpha (TNF-alpha) in 1 of the 5
      SCLC lines (National Cancer Institute (NCI) H211), and upregulated in 2 of the 5
      NSCLC lines (NCI H460 and NCI H838). Among the latter lines, one (NCI H838)
      released significant amounts of sICAM-1. Adhesion to LAK cells and susceptibility
      to LAK cytotoxicity were significantly higher in TNF-alpha-treated NCI H460 and
      NCI H211 cells, compared to untreated NCI H460 and NCI H211 cells. In contrast,
      no difference in adhesion to LAK cells and susceptibility to LAK cytotoxicity was
      detected between baseline and TNF-alpha-treated NCI H838 cells. Intercellular
      adhesion molecule-1 surface expression and soluble intercellular adhesion
      molecule-1 release may play an important role in interactions between lymphokine
      activated killer cells and lung cancer cells.

PMID- 8880100
TI  - Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil
      survival in vitro.
AB  - Mechanisms of eosinophil accumulation and activation in the bronchial mucosa are
      crucial for the pathogenesis of asthma. The location of specialized fibroblasts,
      myofibroblasts, beneath the bronchial basement membrane and their proximity to
      infiltrating eosinophils potentially enable the myofibroblasts to modulate
      eosinophil survival and function in asthma. The aim of this study was to
      investigate the effects of bronchial myofibroblasts on eosinophil survival in
      vitro. Eosinophils from human peripheral blood were exposed to cell cultures from
      bronchial myofibroblasts and to myofibroblast-conditioned media. Eosinophil
      viability was assessed and granulocyte/macrophage colony-stimulating factor (GM
      CSF) production was examined in co-culture supernatants and as messenger
      ribonucleic acid (mRNA) in myofibroblasts. Eosinophil survival was significantly
      increased and eosinophil apoptosis was inhibited by co-culture with
      myofibroblasts. Conditioned medium from tumour necrosis factor-alpha (TNF-alpha)
      stimulated myofibroblasts also prolonged eosinophil survival. This effect could
      be blocked by GM-CSF antibody. GM-CSF mRNA and secretion from myofibroblasts were
      increased in co-cultures and by eosinophil-conditioned medium. Addition of
      antibodies to TNF-alpha and interleukin-1 alpha (IL-1 alpha) to co-cultures
      resulted in significant reduction both in eosinophil survival and GM-CSF levels.
      Blocking of fibronectin in the co-cultures did not affect the eosinophil survival
      enhancing activity. Prednisolone inhibited the eosinophil survival enhancing
      activity of the co-cultures by suppression of GM-CSF production. Soluble
      eosinophil-derived cytokines are involved in the interaction of eosinophils with
      myofibroblasts, which results in a tumour necrosis factor-alpha/interleukin-1
      alpha mediated release of granulocyte/macrophage colony-stimulating factor from
      myofibroblasts. Bronchial myofibroblasts can, thereby, contribute to allergic
      inflammation by granulocyte/macrophage colony-stimulating factor-mediated
      inhibition of eosinophil apoptosis.

PMID- 8880101
TI  - In vivo exposure to nitrogen dioxide (NO2) induces a decrease in calcitonin gene
      related peptide (CGRP) and tachykinin immunoreactivity in guinea-pig peripheral
      airways.
AB  - The mammalian respiratory tract is densely innervated by sensory and autonomic
      fibres. Subsets of the nerves contain bioactive regulatory peptides, such as
      substance P, calcitonin gene-related peptide (CGRP), and neurokinins. The sensory
      nervous system responds to inhaled irritants, resulting in a release of
      neuropeptides and, thus, a decrease in the peptide immunoreactivity of the
      fibres. We examined the effects of inhaled nitrogen dioxide (NO2), a well-known
      indoor and outdoor air pollutant, on pulmonary sensory neuropeptides. Guinea-pigs
      were exposed for 4 h to 18 parts per million (ppm) NO2 or to air (n = 5 each). At
      the end of the exposure, they were killed with urethane and their lungs were
      fixed in 1% paraformaldehyde in phosphate-buffered saline. Cryostat sections were
      stained with antisera to an anatomical nerve marker, protein gene product (PGP)
      9.5, and to CGRP and tachykinins, utilizing the avidin-biotinylated peroxidase
      method. In the noncartilaginous airways (diameter < 250 microns) of NO2-exposed
      animals, less tachykinin- and CGRP-immunoreactive nerve fibres were found
      compared with controls. No change was seen in the total nerve fibre distribution
      (PGP 9.5). It is concluded that the peptidergic nerves of guinea-pig peripheral
      airways are a sensitive indicator of exposure to nitrogen dioxide.

PMID- 8880102
TI  - Effect of short-term NO2 exposure on induced sputum in normal, asthmatic and COPD
      subjects.
AB  - The aim of this study was to assess the effects of short-term exposure to low
      levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal,
      eight mild asthmatic and seven chronic obstructive pulmonary disease (COPD)
      subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2
      for 1 h, with moderate intermittent exercise, on different days and in random
      order. Before and 2 h after exposure, symptom score and results of pulmonary
      function tests (PFTs) were assessed. All subjects performed nasal lavage and
      hypertonic saline (HS) inhalation to collect sputum 2 h after both exposures.
      Asthmatic subjects had a higher percentage of eosinophils than normal and COPD
      subjects in HS-induced sputum after air (asthmatics: median 13 (range 0.4-37)%;
      normals: 0 (range 0-2)%; COPD 1.8 (range 0.1-19)%), whilst COPD patients showed a
      higher percentage of neutrophils than the two others groups. No significant
      differences in PFT values or percentages of inflammatory cells were observed in
      nasal lavage and in HS-induced sputum in normal, asthmatic and COPD subjects
      after NO2 exposure compared to air exposure, except for a mild decrease in forced
      expiratory volume in one second (FEV1) 2 h after NO2 exposure in COPD patients.
      Symptom score showed a mild increase after NO2 exposure both in normal subjects
      and in COPD patients. We conclude that short-term exposure to 0.3 ppm nitrogen
      dioxide does not induce an early detectable acute inflammation in proximal
      airways of normal subjects or of patients with asthma or chronic obstructive
      pulmonary disease.

PMID- 8880103
TI  - Bronchoalveolar and systemic cytokine profiles in patients with ARDS, severe
      pneumonia and cardiogenic pulmonary oedema.
AB  - The aim of this study was to investigate whether bronchoalveolar lavage (BAL) and
      serum levels of proinflammatory cytokines discriminate between different entities
      of patients with acute respiratory failure. BAL and circulating concentrations of
      interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF
      alpha) were measured in 74 mechanically-ventilated patients and 17 healthy
      controls. Patients were classified as cardiogenic pulmonary oedema (CPO), acute
      respiratory distress syndrome (ARDS), primary severe pneumonia (PN) and a
      combined group (PN+ARDS). In all patients with ARDS and/or PN, markedly elevated
      BAL levels of IL-6 and IL-8 were detected, which were significantly greater than
      levels in CPO and healthy controls. Absolute quantities and time-course of these
      cytokines did not differentiate between the absence and presence of lung
      infection, or different categories of PN. Similarly, circulating IL-6 levels were
      comparably elevated in patients with ARDS and/or PN, whereas circulating IL-8
      concentrations were inconsistently increased. TNF-alpha was rarely detected in
      BAL samples, but increased serum concentrations were measured in ARDS and/or PN
      patients. Bronchoalveolar lavage levels of interleukin-6 and interleukin-8, but
      not tumour necrosis factor-alpha, and serum concentrations of interleukin-6 are
      consistently elevated in acute respiratory distress syndrome and/or severe
      pneumonia, discriminating these entities from cardiogenic pulmonary oedema.
      Alveolar and systemic cytokine profiles do not differentiate between acute
      respiratory distress syndrome in the absence of lung infection and states of
      severe primary or secondary pneumonia, which evidently present with comparable
      local and systemic inflammatory sequelae.

PMID- 8880104
TI  - Gastric intramucosal pH: an indicator of weaning outcome from mechanical
      ventilation in COPD patients.
AB  - The aim of this study was to determine whether gastric intramucosal pH (pHim)
      and/or gastric intramucosal carbon dioxide tension (PCO2,im) measured by
      tonometry can be used to predict the success of weaning in chronic obstructive
      pulmonary disease (COPD) patients. Twenty six consecutive COPD patients,
      undergoing mechanical ventilation for acute respiratory failure and satisfying
      the criteria of weaning from mechanical ventilation with nasogastric tonometer in
      place, were studied. Arterial blood gas values and PCO2,im were measured 24 h
      before (H-24), just before (H0), and after 20 min of a weaning trial on T-piece
      (H20min). Weaning failure was defined as the development of respiratory distress
      and/or arterial blood gas impairments during the first 2 h of spontaneous
      breathing on T-piece, or reintubation within 24 h after extubation. Between the
      weaning failure (n = 6) and weaning success (n = 20) groups, there were no
      differences in blood gas analysis readings at H-24 and H0 before the weaning
      period, age, Simplified Acute Physiology Score (SAPS) on admission, SAPS on the
      day of weaning trial, and duration of ventilation. Clinical status, tonometric
      and arterial gasometric data were similar at H-24 and H0 in all patients. During
      mechanical ventilation, pHim was < or = 7.30 in patients who failed weaning and >
      7.30 in patients who were successfully weaned (p < 0.001; 100% sensitivity and
      specificity). The threshold value for PCO2,im of 8.0 kPa (60 mmHg) represents a
      clear demarcation with respect to outcome before the weaning trial. PCO2,im
      values during mechanical ventilation are significantly different (p < 0.001)
      between patients who were successfully weaned and those who were not (6.9 +/- 0.9
      vs 9.9 +/- 1.1 kPa (51.9 +/- 6.7 vs 74.3 +/- 8.0 mmHg, respectively)). At H20min,
      pHim and PCO2,im were still statistically different between the weaning failure
      and the weaning success group. We conclude that measurement of gastric
      intramucosal pH (or gastric intramucosal carbon dioxide tension) represents a
      simple and accurate index to predict weaning outcome in chronic obstructive
      pulmonary disease patients before attempting weaning.

PMID- 8880105
TI  - Mineralogical analysis of the respiratory tract in aluminium oxide-exposed
      workers.
AB  - A retrospective study was conducted in order to characterize the retention of
      fibrous and nonfibrous mineral particles in the respiratory tract in subjects
      with previous occupational exposure in the aluminium industry. Bronchoalveolar
      lavage (BAL) fluid (three samples) or lung parenchyma (two samples) were studied
      using analytical transmission electron microscopy in five patients. A high
      concentration of aluminium fibres (> 10(7) fibres.g-1 dry lung) was identified in
      two lung tissue samples, and aluminium fibres were also identified in BAL fluid
      in three patients. All fibres were short (mean length: 1-2 microns), with no
      fibre longer than 5 microns. Some biopersistence of these fibres in the
      respiratory tract is suggested from these observations, since fibres were
      identified in biological samples collected more than 4 yrs after cessation of
      exposure in four out of five patients. Occupational physicians should be aware of
      possible exposure to short, thin aluminium fibres during primary aluminium
      production. Further studies are needed to assess the potential health effects of
      these fibres. Industrial hygiene measurements should also be performed to
      document the potential sources of exposure to aluminium fibres in this industry.

PMID- 8880106
TI  - Total serum IgE is associated with asthma independently of specific IgE levels.
      The Spanish Group of the European Study of Asthma.
AB  - In this study we aimed to assess whether the association between asthma (defined
      by symptoms and bronchial responsiveness) and total immunoglobulin E (IgE) levels
      was independent of specific IgE levels to common aeroallergens. A general
      population-based sample, supplemented with symptomatic individuals, comprising
      1,916 young adults, aged 20-44 years, from five areas of Spain, performed a face
      to-face respiratory questionnaire, and spirometry, and had total and specific
      serum IgE levels to mites, pets and moulds recorded. In 1,626 of the subjects, a
      dose-response methacholine challenge test was completed. Subjects reporting
      current attacks of asthma showed an association with total IgE (odds ratio (OR)
      for IgE > 100 kU.L-1 = 4.73, 95% confidence intervals (95% CI) = 2.01-11.12,
      adjusted for specific IgE, sex, age, smoking, forced expiratory volume in one
      second (FEV1), and area), which did not vary by bronchial responsiveness. The
      association between total IgE and asthma also occurred among those with negative
      specific IgE antibodies (OR 18.0; 95% CI 13.9-120). Individuals with current
      wheezing and bronchial responsiveness without attacks of asthma also showed an
      adjusted association with total IgE (OR 4.96; 95% CI 2.32-10.6), which remained
      for persons without specific IgE (OR 5.86; 95% CI 2.18-1.7). These findings
      reinforce previous evidence that asthma is associated with increased levels of
      total IgE, even in subjects negative for specific IgE to common aeroallergens.

PMID- 8880108
TI  - Change in osmolarity of disodium cromoglycate solution and protection against
      exercise-induced bronchospasm in children with asthma.
AB  - It has been suggested that osmolarity and/or nebulizer output may affect the
      protective effects of disodium cromoglycate (DSCG) in asthma. The aim of this
      study was to evaluate the influence of osmolarity of the DSCG solution on
      exercise-induced bronchospasm (EIB) in children with bronchial asthma. A jet
      nebulizer was used for DSCG inhalation in Study 1 and an ultrasonic nebulizer in
      Study 2. Thirteen asthmatic children (7 males and 6 females, aged 6-14 yrs) were
      enrolled in Study 1, and nine asthmatic children (5 males and 4 females, aged 9
      13 yrs) in Study 2. After pretreatment with saline (control), hypotonic DSCG or
      isotonic DSCG, children underwent exercise challenge with a cycle ergometer. The
      percentage fall in forced expiratory volume in one second (FEV1) was measured at
      5 and 15 min postexercise. The data were compared by analysis of variance
      (ANOVA). Both in Study 1 and Study 2, there were no significant differences in
      minute ventilation volume or maximum heart rate during exercise between the
      different treatment groups. Both hypotonic and isotonic DSCG significantly
      reduced the maximum percentage fall in FEV1. There were no significant
      differences in protective effects between hypotonic and isotonic DSCG in either
      study. We conclude that the efficacy of hypotonic and isotonic disodium
      cromoglycate solutions is similar for protection against exercise-induced
      bronchospasm. Hypotonic disodium cromoglycate seems to be clinically effective
      for prevention of exercise-induced bronchospasm and treatment of asthmatic
      children.

PMID- 8880107
TI  - Effect of addition of inhaled salmeterol to the treatment of moderate-to-severe
      asthmatics uncontrolled on high-dose inhaled steroids. European Respiratory Study
      Group.
AB  - The aim of this study was to assess the efficacy and safety of inhaled salmeterol
      100 micrograms b.d. (SM) versus inhaled salbutamol 400 micrograms q.d.s. (SB),
      both via the Diskhaler, when added to concurrent treatment, in asthmatic patients
      who were not controlled on high doses of inhaled steroids (> or = 1,500
      micrograms beclomethasone dipropionate (BDP) or equivalent daily). This was a
      multicentre, parallel group, double-blind study in which 190 patients with a
      forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR)
      of 30-75% predicted and 15% reversibility to inhaled bronchodilator were
      randomized to treatment for 6 weeks. In the SM group, morning PEFR increased from
      281 to 315 L-min-1 during treatment and in the SB group from 311 to 315 L.min-1
      (p < 0.001). The SM group showed significantly better reduction in diurnal
      variation, from 39 to 22 L.min-1 during treatment, than the SB group (34 to 37
      L.min-1) (p < 0.001). There was a significantly greater improvement in FEV1 in
      the SM group (from 1.63 to 1.85 L) than in the SB group (from 1.79 to 1.84 L).
      The SM group had significantly more symptom-free nights than the SB group (p <
      0.001), and also more "rescue-free" nights (p = 0.04). The adverse event profile
      was similar in both groups. This study indicates that in asthmatic patients, not
      controlled on high-dose inhaled steroids, inhaled salmeterol 100 micrograms b.d.
      significantly improves lung function and reduces asthma symptoms.

PMID- 8880109
TI  - Comparison of bronchial challenge with ultrasonic nebulized distilled water and
      hypertonic saline in children with mild-to-moderate asthma.
AB  - There is still controversy about the most suitable method to measure bronchial
      hyperresponsiveness in children. In epidemiological surveys, nonisotonic aerosols
      are being used increasingly for bronchial provocation testing. Our aim was to
      study the acceptability, safety and correlation between two published bronchial
      challenge tests. Two standardized protocols--the inhalation of hypertonic saline
      (HS) and ultrasonically-nebulized distilled water (UNDW)--were performed in 36
      children: 19 patients with the clinical diagnosis of mild-to-moderate asthma (7
      12 yrs of age), and 17 control subjects (8-18 yrs of age). HS challenge involved
      stepwise inhalation of 4.5% saline (for 0.5, 1, 2, 4 and 8 min), whereas
      challenge with UNDW was performed as a single step protocol with 10 min
      inhalation of cold UNDW. Asthma medication was withheld prior to challenge
      testing. Thirty five subjects completed both challenge tests (one asthmatic
      patient did not return after UNDW challenge) in random order within a 7 day time
      interval. For HS a > or = 15% reduction in forced expiratory volume in one second
      (FEV1) from baseline was considered a positive response, and for UNDW a > or =
      10% decrease. In 13 of the 19 asthmatic patients, but in none of the controls, a
      positive response was observed for UNDW. Fifteen out of 18 patients and one
      control subject had a positive response to HS. Twelve out of 18 asthmatic
      children responded to both challenges, three responded only to HS and three had
      no response to either challenge. There was a negative correlation between log
      provocative dose causing a 15% reduction in FEV1 (PD15) after HS and the maximum
      fall in FEV1 after UNDW (rs = -0.63; p < 0.005). The HS challenge had a lower
      acceptability than challenge with UNDW due to the unpleasant salty taste of HS.
      However, this did not inhibit the completion of the tests in any subject. The
      results of this study suggest a good correlation between response to hypertonic
      saline and ultrasonically-nebulized distilled water in children with mild-to
      moderate asthma. A multiple step protocol might be safer when applied in field
      studies involving children.

PMID- 8880110
TI  - Effect of pattern of preceding inspiration on FEV1 in asthmatic children.
AB  - In adults, both peak expiratory flow (PEF) and forced expiratory volume in one
      second (FEV1) are significantly influenced by the time course of the inspiration
      preceding the forced expiration. The aim of this study was to evaluate the
      effects of three different inspiratory manoeuvres on PEF, FEV1, and forced vital
      capacity (FVC) in asthmatic children. Twenty five symptomless asthmatic children
      performed forced expiration preceded by three different inspiratory manoeuvres,
      which consisted of: a rapid inspiration with a 2 s end-inspiratory breathhold
      (Manoeuvre No. 1); a rapid inspiration without an end-inspiratory breathhold
      (Manoeuvre No. 2); and a slow inspiration lasting about 5 s with an end
      inspiratory breathhold of at least 4 s (Manoeuvre No. 3). All manoeuvres were
      performed in a randomly assigned sequence each morning for three consecutive
      days. In each session, the manoeuvres were repeated three times and the highest
      value was chosen. Both FVC and FEV1 obtained with Manoeuvre No. 3 were
      significantly lower than the corresponding values obtained with Manoeuvre Nos. 1
      and 2. The mean (SD) FVC values were 2.76 (0.66) L with Manoeuvre No. 1, 2.67
      (0.58) L with Manoeuvre No. 2 and 2.52 (0.52) L with Manoeuvre No. 3. The
      corresponding values of FEV1 were 2.25 (0.53), 2.22 (0.53) and 2.07 (0.44) L,
      respectively. By contrast, the values of PEF, obtained with a portable peak flow
      meter, were similar with the three different inspiratory manoeuvres. The results
      of this study show that in symptomless asthmatic children the preceding
      inspiratory manoeuvre may influence forced vital capacity and forced expiratory
      volume in one second. Hence, in order to reduce variability due to interference
      by physiological factors and so improve reproducibility of pulmonary function
      tests, the inspiratory manoeuvres must be accurately standardized.

PMID- 8880111
TI  - Cysteinyl leukotriene involvement in chronic lung disease in premature infants.
AB  - The pathophysiology of chronic lung disease (CLD) in premature infants who
      require mechanical ventilation and prolonged oxygen supplementation has been well
      described but the underlying mechanisms are not understood. Our aim was to test
      the hypothesis that excess cysteinyl leukotriene (LT) production was a
      contributing factor in CLD. We compared LT production and lung function, at 7
      months of age, in nine premature infants with CLD and in eight control infants
      without CLD. None of the control infants developed any neonatal respiratory
      problems, but two subsequently required bronchodilator therapy. Respiratory
      function was assessed by the measurement of thoracic gas volume (TGV), airways
      resistance (Raw) and functional residual capacity (FRC). Total cysteinyl LT
      production was quantified by measurement of leukotriene E4 (LTE4) in a spot urine
      sample. Although all patients were asymptomatic at follow-up, there was evidence
      of significant lung function abnormalities in infants with CLD. The CLD infants
      had significantly elevated TGV, Raw and FRC values reflecting airway obstruction
      when compared to the controls. Urinary LTE4 levels were significantly higher in
      the CLD infants when compared to the controls (geometric mean: 741 and 337
      pmol.mmol-1 creatinine, respectively). There was no direct correlation between
      urinary LTE4 levels in the CLD group and TGV, Raw or FRC values. Although this
      study is small and a direct correlation between lung function and urinary
      leukotriene E4 was not demonstrated, pathological lung function and an enhanced
      urinary leukotriene E4 production in infants with chronic lung disease would tend
      to suggest that the cysteinyl leukotrienes were involved in the sequelae of this
      disease.

PMID- 8880113
TI  - Weaning from mechanical ventilation.
AB  - Weaning from mechanical ventilation is a period of transition from total
      ventilatory support to spontaneous breathing. It represents a relevant clinical
      problem because as many as 25% of intubated and mechanically-ventilated
      critically ill patients will need a progressive withdrawal from artificial
      ventilatory support. From a clinical standpoint, it is very important to
      recognize as soon as possible when a patient is ready to be weaned. Accordingly,
      a daily routine follow-up should be performed in every patient in order to verify
      whether patients meet clinical criteria to be disconnected from the ventilator.
      Several physiological indices have been used to predict the outcome of weaning
      trials. However, an adequate clinical tolerance to spontaneous breathing during a
      2 h T-piece trial is very useful to predict a successful extubation. A number of
      physiopathological mechanisms explain why some patients fail the weaning trials;
      particularly important from a clinical point of view are those related to
      respiratory pump failure and cardiovascular instability, which are usually
      accompanied by an abnormal gas exchange. Different ventilatory techniques can be
      used to wean these patients from mechanical ventilation. Up to now, the most
      efficient techniques seem to be pressure support ventilation and once daily
      trials of T-piece interspersed with conventional volume assist-control
      ventilation. Finally, knowledge-based system applied to modern microprocessor
      mechanical ventilators can help in the process of weaning by automatically
      reducing the ventilatory assistance and indicating the optimal time to perform
      extubation.

PMID- 8880112
TI  - Bacterial-induced release of inflammatory mediators by bronchial epithelial
      cells.
AB  - This review focuses on bacterial induction and release of inflammatory cytokines
      and adhesion molecules by human bronchial epithelial cells, with special
      reference to Haemophilus influenzae, a pathogen commonly associated with chronic
      bronchitis. Studies investigating the mechanisms underlying bacterial
      colonization of the airways and bacterial-induced chronic airway inflammation
      have suggested that these are likely to involve localization of bacteria to the
      site(s) of infection in the respiratory tract and induction of a local airway
      inflammation resulting in the initiation of epithelial damage. We have
      hypothesized that the gross airway epithelial damage observed in chronic
      infective lung disease is an indirect consequence of proteolytic enzymes and
      toxic oxygen radicals generated by large numbers of neutrophils infiltrating the
      airways. Furthermore, the infiltration and activation of the neutrophils is a
      consequence of increased release of proinflammatory mediators from the host
      respiratory epithelium, induced by bacterial products, such as endotoxin. This
      hypothesis is based on studies which have demonstrated that the concentrations of
      circulating cytokines, such as interleukin (IL)-8 and tumour necrosis factor
      alpha (TNF-alpha), which have profound effects on neutrophil activity, are
      increased in endotoxaemia and that airway epithelial cells are a rich source of
      these cytokines. Support for this hypothesis is provided by studies of cultured
      human bronchial epithelial cells incubated either in the absence or presence of
      purified endotoxin preparations from nontypable and type b H. influenzae strains
      which have demonstrated that these endotoxins lead to significantly increased
      expression and/or release of proinflammatory mediators, including IL-6, IL-8, TNF
      alpha and intercellular adhesion molecule-1 (ICAM-1). Treatment of the cells with
      steroids can downregulate the expression and/or release of these inflammatory
      mediators. Additionally, these studies have demonstrated that culture medium
      collected from endotoxin-treated cultures, 24 h after treatment, significantly
      increases neutrophil chemotaxis and adhesion to human endothelial cells in vitro.

PMID- 8880114
TI  - The epidemiology of mesothelioma in historical context.
AB  - Primary malignant mesothelial tumours were recognized by pathologists before
      asbestiform minerals (chrysotile, crocidolite and amosite) were mined
      commercially. The discovery, 40 yrs ago, of a causal link with crocidolite and
      the wide-ranging epidemiological studies which followed are the subject of this
      review. Early case-control and descriptive surveys, supplemented by cohort
      studies in insulation workers and chrysotile miners, quickly demonstrated major
      occupational and geographical differences, with high risk in naval dockyard areas
      and in the heating trades. In the 1980s, reliable cohort surveys showed that in
      mining and in the manufacture of asbestos products the mesothelioma risk was much
      higher when exposure included crocidolite or amosite than chrysotile alone.
      However, qualitative and quantitative information on exposure was too often
      inadequate for this evidence to be conclusive. Well-controlled lung fibre
      analyses have reduced these deficiencies and demonstrated the probable
      implications of the greater biopersistence of amphibole fibres. Chrysotile for
      industrial use often contains low concentrations of fibrous tremolite, which may
      well explain the few cases of mesothelioma associated with this type of asbestos.
      Progress in this field has been much retarded by controversy, for which the 20
      year gap between the availability of reliable estimates of risk for the mining of
      chrysotile and that for crocidolite or amosite may have been largely responsible.

PMID- 8880115
TI  - Electrostatic charge on a plastic spacer device influences the delivery of
      salbutamol.
AB  - The aim of this study was to determine whether electrostatic charge on a plastic
      spacer decreases the delivery of salbutamol from a pressurized metered-dose
      inhaler (pMDI) and, if so, to find an optimal and practical treatment to remove
      the charge. Ten single actuations from a salbutamol pMDI were drawn through
      different Volumatic spacers at a constant flow of 60 L.min-1. The efficacies of
      different methods of removing charge were tested, including detergent coating of
      the spacers. A multistage liquid impinger was used to determine the particle size
      distribution of the output of the pMDI through the Volumatic spacers. The
      electrostatic charge on the inner surface of the spacers was measured both
      quantitatively with an electrometer, and qualitatively by the attraction of a
      thin strip of cellulose membrane to the wall of the spacer. Each experiment was
      repeated four times. Ionic detergent coating of the spacers removed the charge
      for at least 24 h. This resulted in an increase of 55-70% in small particle (<
      6.8 microns) delivery compared to delivery from new spacers with high charge. We
      have demonstrated that electrostatic charge plays a major role in the delivery of
      salbutamol through plastic spacers. Adequate treatment with ionic detergent
      removes the charge and improves drug delivery.

PMID- 8880116
TI  - Endothelin-1 and interleukin-8 in high altitude pulmonary oedema.
AB  - We present a case of high altitude pulmonary oedema (HAPE) with pulmonary
      hypertension and polymorphonuclear leucocyte (PMN) accumulation in
      bronchoalveolar lavage fluid (BALF), which occurred in a 21 year old man. Plasma
      endothelin-1 (ET-1) and interleukin-8 (IL-8) concentration in BALF were elevated
      on admission, and returned to normal level at recovery, when the pulmonary artery
      pressure and the PMN counts in BALF were normal. In addition, E-selectin and
      intercellular adhesion molecule-1 (ICAM-1) in BALF were also slightly increased
      on admission. These findings suggest that endothelin-1 is a vasoconstrictor which
      contributes to the pulmonary hypertension in high altitude pulmonary oedema, and
      that some of the inflammatory mediators play an important role in chemotaxis and
      accumulation of polymorphonuclear leucocytes in the development of high altitude
      pulmonary oedema.

PMID- 8880117
TI  - Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage
      fluid of a patient with ANCA negative Wegener's granulomatosis.
AB  - We report a case of Wegener's granulomatosis (WG), with neutrophil accumulation
      in bronchoalveolar lavage fluid (BALF). Peripheral blood neutrophilia was present
      but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and
      BALF levels of neutrophil-related cytokines, including interleukin (IL)-8,
      granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, were increased,
      particularly in BALF. Plasma and BALF levels of neutrophil elastase and
      defensins, which are released by neutrophils and are potentially toxic to cells,
      were also elevated. Our findings suggest that neutrophils and neutrophil-related
      cytokines may play an important role in the pathogenesis of anti-neutrophil
      cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody
      positive Wegener's granulomatosis.

PMID- 8880118
TI  - Association between Wegener's granulomatosis and Staphylococcus aureus infection?
AB  - Two patients are presented with Wegener's granulomatosis (WG) and lower
      respiratory tract infections with Staphyloccus aureus (SA). It is posulated that
      there is a relationship between the infection and the induction or relapse of the
      disease. We suggest that bronchoalveolar lavages should be performed in cases of
      suspected WG to identify SA-infections. The co-existence of WG and SA support the
      reported beneficial effects of sulfamethoxazole/trimethoprim, but needs further
      evaluation in patients with and without SA-infection of the airways.

PMID- 8880119
TI  - Common variable immunodeficiency presenting in a girl as lung infiltrates and
      mediastinal adenopathies leading to severe "superior vena caval" syndrome.
AB  - Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder
      characterized by decreased levels of circulating immunoglobulins (Ig) and
      increased susceptibility to infections. We describe the case of a girl,
      progressively developing CVID, whose first clinical manifestations were
      noninfectious diffuse pulmonary infiltrates and rapidly developing hilar and
      mediastinal lymphadenopathies causing a severe "superior vena caval syndrome".
      Histological evaluation of surgical samples showed follicular and paracortical
      hyperplasia of the lymph nodes and poorly organized, non-necrotizing,
      noninfectious, "reactive" granulomata in lymph nodes and pulmonary tissue. Daily
      treatment with azathioprine and prednisone induced resolution of the
      intrathoracic abnormalities but was associated with a progressive decrease of
      circulating IgG and IgA levels and natural killer (NK) lymphocytes that was not
      related to treatment. This case demonstrates that granulomatous inflammatory
      changes may be the first manifestations of common variable immunodeficiency, and
      that this disorder must be included in the differential diagnosis of lymphoid
      interstitial pneumonitis and of bilateral mediastinal lymph node enlargement
      leading to superior vena caval syndrome.

PMID- 8880120
TI  - A boy with chest deformity.

PMID- 8880121
TI  - The NO donor sodium nitroprusside reverses the negative effects on hepatic
      arterial flow induced by endotoxin and the NO synthase inhibitor L-NAME.
AB  - In previous studies we have observed that the nitric oxide synthase inhibitor L
      NAME induces a profound deterioration of liver circulation in experimental
      endotoxemia. Using the same porcine model we now have evaluated the possibility
      of modulating these effects with the nitric oxide donor sodium nitroprusside.
      Infusion of endotoxin led to a gradual deterioration of hemodynamic parameters,
      including liver blood flow. The decreases in portal blood flow paralleled and
      matched the decreases in cardiac output, and no compensatory increase in hepatic
      arterial flow occurred. L-NAME had detrimental effects on hemodynamics, including
      the liver circulation. The latter effects could, however, partially be reversed
      by sodium nitroprusside. Hepatic arterial flow increased from 1.9 to 7.2
      ml/kg/min, with a concomitant decrease in hepatic arterial resistance from 5,364
      to 1,746 dyn s/cm5 kg. A control group exhibited no significant change in either
      flow or resistance. The response to sodium nitroprusside was rapid and vigorous,
      and probably largely due to relaxation of the hepatic arterioles, and not to
      abatement of intrahepatic edema or plugging of the sinusoids. Furthermore, we
      conclude that the endotoxin-induced dysfunction of the hepatic arterial buffer
      response may be due to a selective inhibition of vascular endothelial function.

PMID- 8880122
TI  - Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with
      special reference to histological morphometric analysis and galactose elimination
      capacity.
AB  - To evaluate liver dysfunction in patients with obstructive jaundice (OJ),
      morphological and functional hepatic mass was analyzed in comparison with
      cirrhosis (LC). Total hepatic parenchymal ratio (THPR) was estimated by
      morphometric analysis and hepatic functional mass by galactose tolerance test
      (GaTT) in 30 patients who underwent hepatectomy. The value of GaTT in patients
      with LC was remarkably depressed compared to those with normal liver function (p
      < 0.001). It was also depressed in OJ (p < 0.05 vs. normal liver), but less than
      in LC (p < 0.05). However, THPR decreased only in LC (p < 0.05 vs. either normal
      liver or OJ). A significant correlation between the value of GaTT and THPR was
      revealed in patients with LC, but not in OJ. These results suggested that liver
      dysfunction in OJ was independent of the decreased number of hepatocytes,
      differing from LC.

PMID- 8880123
TI  - Endogenous endotoxemia after massive hepatectomy and portal vein stenosis:
      beneficial effect of a prostaglandin I2 analogue on intestinal permeability.
AB  - Portal vein (PV) stenosis may contribute to operative death after extended
      hepatectomy combined with PV reconstruction leading to impairment of the
      intestinal mucosal barrier. This study was designed to investigate whether rats
      undergoing such surgery developed endogenous endotoxemia and increased intestinal
      permeability. The effect of a prostaglandin I2 (PGI2) analogue on mucosal barrier
      function was also studied. The rats were divided into the following five groups:
      sham operation, massive hepatectomy (Ht), PV stenosis (PS), combined Ht and PS
      (Ht+PS), and Ht+PS with subcutaneous injection of PGI2 preoperatively (PG). The
      10-day survival rate, portal endotoxin level and intestinal permeability (two
      sugar test) were evaluated in each group. The Ht+PS group showed a significant
      increase in both the portal endotoxin level and intestinal permeability (p <
      0.05) and a significant worse 10-day survival (p < 0.01) than the other four
      groups. PGI2 pretreatment did not influence splanchnic blood flow, but decreased
      the endotoxin level and reduced intestinal permeability. In conclusion, the
      synergistic effect of massive hepatectomy and PV stenosis induced an increased
      intestinal permeability and consequently endotoxemia. PGI2 pretreatment
      significantly improved both intestinal barrier function and survival.

PMID- 8880124
TI  - Effect of intraperitoneal antimicrobials on the concentration of bacteria,
      endotoxin, and tumor necrosis factor in abdominal fluid and plasma in rats.
AB  - The efficacy of intraperitoneal instillation of antimicrobial agents in
      eliminating the bacterial contaminant in patients with generalized peritonitis
      remains controversial. We determined the effect of intraperitoneal instillation
      of taurolidine or imipenem on mortality, and on the concentration of bacteria,
      endotoxin, and tumor necrosis factor (TNF) in rats with intraperitoneally
      injected bacteria. Thirty rats were inoculated intraperitoneally with two enteric
      bacterial strains, followed by either taurolidine, saline, or imipenem. Abdominal
      fluid and blood were analyzed at different time intervals. The survival rate was
      highest in the imipenem group (p < 0.05). The bacterial concentration in
      abdominal fluid in the taurolidine and imipenem group was lower than in the
      saline group (p < 0.005), but the concentration in the imipenem group was lowest
      (p < 0.005). The endotoxin concentration in abdominal fluid and plasma in the
      taurolidine group was lower than in the other two groups (p < 0.05). The TNF
      concentration in abdominal fluid and plasma in the taurolidine group was lower
      than in the saline group (p < 0.05), whereas the concentration in the imipenem
      group was higher (p < 0.005). We conclude that topically applied taurolidine in
      rats with intraperitoneally injected bacteria may have a weak antibacterial
      effect, and lowered concentrations of endotoxin and TNF. Topically applied
      imipenem had a profound bactericidal activity but induced endotoxin and TNF
      release.

PMID- 8880125
TI  - Role of interleukin-6 in skeletal muscle protein breakdown and cathepsin activity
      in vivo.
AB  - In order to elucidate the acute and chronic effects of interleukin-6 (IL-6) on
      muscle protein degradation, the weight of skeletal muscles and the activities of
      lysosomal cathepsins (B and L) in the muscles were examined in two animal models.
      Two intraperitoneal injections of recombinant human IL-6 into rats did neither
      significantly affect the cathepsin activities in the soleus and the extensor
      digitorum longus muscles nor the weight of these muscles. On the other hand, the
      gastrocnemius muscles of the IL-6 transgenic mice underwent severe atrophy
      accompanied by a marked increase in cathepsin activities. We conclude that IL-6
      mediates muscle protein degradation with enhancing lysosomal cathepsin activity,
      and that these muscle reactions are mandated by chronic exposure to a high level
      of IL-6.

PMID- 8880126
TI  - Selective microsurgical sympathetic denervation of the rat pancreas.
AB  - Autonomic nerves have been implicated in the regulation of endocrine and exocrine
      pancreatic secretion. The purpose of the present study was, therefore, to develop
      a simple, reproducible technique for selective sympathetic denervation of the rat
      pancreas. Under ether anesthesia a midline laparotomy was performed, the pancreas
      and spleen were freed from adhesions. The peritoneum was incised over the
      superior and inferior pancreaticoduodenal arteries and the splenic artery at
      their origin. The incised areas were stained with 1% toluidine blue solution. The
      pancreaticoduodenal and splenic nerves were visualized and resected. 1, 2 and 3
      weeks after the denervation procedure the norepinephrine (NE) content of the
      pancreatic tissue was determined. Cholinergic and nitric oxide synthetase (NOS)
      immunoreactive nerve structures were identified by immunohistochemistry 1 week
      after denervation. In denervated tissue the NE content after 1 week was 98% lower
      than measured in controls. With time, there was a gradual increase of the NE
      content, although it reached only 25% of the values measured in sham-operated
      animals at 3 weeks. There was no concomitant denervation of the duodenum.
      Cholinergic and NOS nerve structures were still present 1 week after denervation.

PMID- 8880127
TI  - Influence of intraperitoneal 5-fluorouracil plus folinic acid on the healing of
      colonic anastomoses in rats.
AB  - We studied the effects of intraperitoneal 5-fluorouracil (5-FU) administration
      with or without the addition of folinic acid (FA) on the healing of colonic
      anastomoses in rats immediately after surgery. Sixty-three male Wistar rats were
      subjected to colonic anastomosis. During surgery, the rats were randomized into
      one of three groups. Therapy was administered as an intraoperative
      intraperitoneal injection which was repeated once daily for the first 2
      postoperative days. A 0.9% NaCl solution was administered to the rats in the
      control group. In group 2, we injected 5-FU (20 mg/kg/day) and in group 3 5-FU
      (20 mg/kg/day) plus FA (2 mg/kg/day). The rats were sacrificed on postoperative
      days 3, 5 or 8. Rupture of the anastomosis was significantly higher in the rats
      of groups 2 and 3, compared with the control group (p < 0.05). There were,
      however, no differences between groups 2 and 3. Formation of adhesions and
      abscesses was more common in groups 2 and 3 than in the control group for all
      study days. A significant difference in the anastomotic bursting pressure was
      measured for the control group in comparison to groups 2 and 3 on days 5 and 8 (p
      < 0.05). Histologic evaluation also showed a more profound inflammatory reaction
      and delayed healing of the anastomoses in groups 2 and 3, compared to the control
      group. Therefore, the perioperative intraperitoneal administration of 5-FU can
      inhibit the healing of colonic anastomoses in rats. The addition of an
      intraperitoneal injection of FA does not aggravate this negative effect.

PMID- 8880128
TI  - Different fibrinolytic potentials between human umbilical vein endothelial cells
      and human adult vein endothelial cells.
AB  - Endothelial cells play a central role in fibrinolysis due to their production of
      both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type
      1 (PAI-1). The purpose of this study was to test the hypothesis that the
      production of t-PA and PAI-1 from human umbilical vein endothelial cells (HUVEC)
      and from human adult vein endothelial cells (HAVEC) adopt the same pathways for
      the regulation of fibrinolysis, and that differences in PAI-1 and t-PA production
      are only quantitative. HUVEC and HAVEC cultures were exposed to phorbol ester
      (PMA), endotoxin (LPS) or thrombin, singly or in combination with forskolin or
      H7. The conditioned medium was collected after 16 h and analyzed for t-PA and PAI
      1 antigens. The basal production of both t-PA and PAI-1 was significantly higher
      from HUVEC than from HAVEC. Exposure to PMA, thrombin or forskolin gave a similar
      response from the two cell types. In contrast, the results from HUVEC and HAVEC
      differed significantly, not only in magnitude but also in direction, when the
      cells were exposed to forskolin coincubated with PMA, LPS or thrombin, and in
      magnitude alone when exposed to LPS only. The results indicate that there are not
      only quantitative but also qualitative differences in the production of t-PA and
      PAI-1 from HUVEC and HAVEC. These differences must be taken into account when
      data from cells of different origin are compared.

PMID- 8880129
TI  - Preischemic bolus application of piroximone studied on the isolated rabbit heart-
      a second look including biochemical data.
AB  - In a randomized prospective experimental study on 48 adult white Elco rabbits
      biochemical and rhythmic changes after bolus administration of the
      phosphodiesterase inhibitor piroximone were investigated using a working heart
      model. The treatment group (n = 21) intravenously received 1 mg/kg of piroximone
      15 min before thoracotomy. Twenty-three untreated hearts served as the control
      group. From 6 hearts of each group myocardial biopsies were taken before
      ischemia, 4 (2/2) hearts were excluded. Hemodynamic results of a previous study
      with an identical protocol were reanalyzed; a biochemical analysis of myocardial
      high-energy phosphates was investigated after 60 min of global ischemia and at
      the end of the experiments after 45 min of reperfusion. Already prior to
      ischemia, in the treatment group depletion of high-energy phosphates was
      detected. After 60 min of ischemia during early reperfusion in the treatment
      group ATP and creatine phosphate depletion became even more evident and increased
      until the end of the experiments. The incidence of reperfusion-induced
      arrhythmias was significantly lower in the treatment group. Consequently these
      results and the hemodynamic results of prior studies indicate a possible positive
      effect of piroximone during the early reperfusion period by optimizing
      hemodynamics and arrhythmias.

PMID- 8880130
TI  - Vaccines against protozoal diseases of veterinary importance.
AB  - Protozoan parasites are important animal and human pathogens. At present, most of
      these infections are controlled by chemotherapy. In addition, vaccines are
      available for some of these diseases. There is, however, still an urgent need for
      the development of vaccines against protozoal diseases, since the current array
      of available vaccines is very limited. This review describes the different
      approaches that have been taken to develop such vaccines and discusses the
      difficulties that hampered vaccine development. Many of the problems are related
      to the complex life cycle of these parasites and the virtual lack of mass in
      vitro culture systems. We also give an overview of the commercial and non
      commercial vaccines that do exist at present. Finally, we describe the future
      directions of this interesting field. New techniques and strategies include
      parasite cultivation methods and recombinant-DNA techniques, such as vector
      vaccines and DNA-vaccines. Moreover, these approaches are complemented by the
      development of sophisticated adjuvants; the coupling of immunoprotective
      molecules to entities with adjuvant activity or the use of cytokines, e.g. IL-12.
      Through these innovations new vaccines against protozoal diseases will become
      available in the near future.

PMID- 8880131
TI  - Use of polymorphic short and clustered coding-region microsatellites to
      distinguish strains of Candida albicans.
AB  - We describe the identification of polymorphic microsatellite loci in the
      pathogenic yeast, Candida albicans. A search for all coding-region
      microsatellites with more than four repeats that can be found in Candida
      sequences in GenBank was conducted. Nine such microsatellite sequences consisting
      of trinucleotide motifs were found. Three of these were perfect microsatellites
      while the remaining six sequences were found in one imperfect microsatellite and
      two compound microsatellites. Because of the close proximity of some of these
      repeats, all could be assayed with six PCR primer pairs. All of these
      microsatellite sequences were found in five nuclear genes, ZNF1, CCN1, CPH1,
      EFG1, and MNT2. Except for a single (CTT)5 serine tract, all coded for
      polyglutamine tracts. Another locus with seven alleles, a region of the ERK1
      protein kinase gene, was also examined, and may be a representative of a new
      class of highly polymorphic "clustered' microsatellites. Such loci, in which
      several non-contiguous but closely linked microsatellites are clustered together,
      may be a useful source of DNA polymorphisms in microorganisms in which long
      microsatellite sequences are unavailable. All seven regions amplified were
      polymorphic, having between two and seven variable length alleles in the 11
      strains of Candida albicans examined. The results of this and similar searches
      will facilitate epidemiological and evolutionary studies of Candida and other
      microorganisms.

PMID- 8880132
TI  - Isolation of a new superantigen with potent mitogenic activity to murine T cells
      from Streptococcus pyogenes.
AB  - A mitogenic substance on murine lymphocytes was detected in the culture supernate
      of Streptococcus pyogenes type 12 strain. This substance had a molecular weight
      of 28,000 and pI 9.2, and was designated as S. pyogenes mitogen (SPM). The
      proliferative response of C3H/HeN spleen cells began at 1 ng ml-1 and reached a
      maximal response at 100 ng ml-1 of SPM for 4 days culture. Anti-Thy 1.2 mAb and
      complement-treated spleen cells abrogated the proliferative response to any dose
      of SPM. Although the anti-major histocompatibility complex class 1 mAbs had no
      blocking effect on proliferation by SPM, this proliferation was substantially
      inhibited by the addition of either anti-I-A or anti-I-E mAb, and complete
      inhibition was produced by the addition of both mAbs. Fixed antigen-presenting
      cells still induced T cell proliferation by SPM. A significant expansion of T
      cells bearing V beta 13 T-cell receptor was observed up to 73% among the Thy 1.2+
      cells in cultures stimulated with SPM, indicating expansion in a V beta-specific
      manner. Immunoblotting of IEF-separated proteins showed that anti-streptococcal
      pyrogenic exotoxin (SPE) C reacted with a protein of pI 6.9 and anti-SPEB did not
      show any reactivity. SPEA was reported to expand V beta 8.1 and 8.2 bearing
      murine T cells, and SPM did not. SPM also exhibited potent mitogenic activity on
      human T cells and V beta 21+ T cells were selectively expanded. These results
      lead to the conclusion that SPM was neither SPEA, B nor C, but a new protein
      belonging to a group of streptococcal superantigens with activity on not only
      human but also murine lymphocytes.

PMID- 8880133
TI  - Kupffer cells play important roles in the metabolic degradation of a soluble anti
      tumor (1-->3)-beta-D-glucan, SSG, in mice.
AB  - Metabolic degradation of a soluble highly branched (-->3)-beta-D-glucan, SSG, was
      examined in mice using a macrophage blocker, gadolinium chloride (GdCl3).
      Intraperitoneally administered SSG distributed in the liver was slowly degraded,
      and after 5 weeks about 30% of the SSG became anionic. In addition, it is
      suggested that the metabolites would contain fewer branching points as assessed
      by the reactivity to limulus factor G. On the other hand, in the spleen, the
      molecular weight and the degree of branching of SSG were not changed for at least
      5 weeks. Blockade of Kupffer cells by GdCl3 did not significantly change the
      distribution ratio of SSG in the liver. However, the treatment significantly
      delayed the degradation of SSG. These results suggested that Kupffer cells play
      important roles, not in the distribution, but in the oxidative degradation of SSG
      in the liver. In addition, splenic macrophages did not significantly contribute
      to the metabolic degradation of SSG.

PMID- 8880134
TI  - In situ expression of interleukin-10 and interleukin-12 in active human cutaneous
      leishmaniasis.
AB  - Th1-type cellular immune responses (interferon-gamma) play a critical role in
      protection against Leishmania spp. infection, whereas Th2-type cytokines
      (interleukin (IL)-4, IL-10) have a counter-protective effect. IL-12, a potent
      inducer of Th1-type cellular immune responses, may play a pivotal role in the
      development of a protective response. We found that IL-10 and IL-12 mRNAs were
      expressed in most lesions of individuals with active cutaneous leishmaniasis. The
      quantity of IL-12 mRNA was highly variable but correlated strongly with the level
      of interferon-gamma expression. IL-12 expression also paralleled the expression
      of IL-10, a potent in vitro suppressor of IL-12 and interferon-gamma production.
      The more chronic, non-healing lesions generally had higher levels of IL-12 mRNA
      indicating that the expression of this cytokine alone was not sufficient to
      induce healing. Although the in situ production of IL-10 did not appear to block
      IL-12 expression, IL-10 may still promote disease by direct suppression of
      macrophage activation.

PMID- 8880135
TI  - Endogenous gamma interferon and interleukin-10 in Brucella abortus 2308 infection
      in mice.
AB  - CD-1 mice intravenously infected with the virulent Brucella abortus 2308 strain
      simultaneously produce significant levels of gamma interferon (IFN-gamma) and
      interleukin-10 (IL-10) in their spleens between the second and eighth day post
      infection with no production of interleukin-4 (IL-4). Endogenous synthesis of IL
      10 does not affect the production of IFN-gamma in this organ, while the
      production of both cytokines during this period of time is accompanied by a
      statistically significant increase (P < 0.001) in the number of colony forming
      units (cfu) of B. abortus 2308 present in the organ. These findings suggest that
      although the endogenous synthesis of IL-10 apparently does not affect IFN-gamma
      production, it may affect the effector functions of macrophages to control
      intracellular brucellae. Production of the Th1 cytokine IFN-gamma during B.
      abortus 2308 infection is also associated with a specific IgG3 and IgG2a response
      against the B. abortus 2308 lipopolysaccharide (S-LPS) antigen.

PMID- 8880136
TI  - Detection of measles virus-induced apoptosis of human monocytic cell line (THP-1)
      by DNA fragmentation ELISA.
AB  - Measles virus (wild strain, Toyoshima strain)-induced cell death is characterized
      by cell shrinkage, chromatin condensation, and nuclear fragmentation in a human
      monocytic cell line (THP-1). DNA fragmentation of measles virus-infected THP-1
      cells was demonstrated by DNA agarose gel electrophoresis as well as by DNA
      fragmentation ELISA. When measles virus-infected THP-1 cells were cultured on
      monolayers of fibroblasts or human umbilical vein endothelial cells (HUVEC), the
      percentage of measles virus antigen-positive THP-1 cells and DNA fragmentation
      were significantly decreased. Addition of anti-intercellular adhesion molecule
      (ICAM)-1 (CD54) monoclonal antibody to culture of measles virus-infected THP-1
      cells reduced significantly DNA fragmentation induced by measles virus. These
      findings suggest that inhibition of virus spread by fibroblasts and HUVEC reduces
      apoptosis, and ICAM-1 (CD54) may participate in the DNA fragmentation pathway.

PMID- 8880137
TI  - Contamination with Mycoplasma spp. induces interleukin-13 expression by human
      skin fibroblasts in culture.
AB  - The mycoplasmas comprise a discrete group of microorganisms that are known to
      exert a range of effects upon cells derived from the immune system. Some of these
      interactions turn out to be immunomodulatory, such as polyclonal stimulation of T
      and B cells or enhancement of the cytolytic potential of macrophages, NK cells
      and T lymphocytes. Immunologically committed cells, when infected with
      mycoplasmas, can also increase the production of cytokines (IL-1, IL-2, IL-4 and
      IL-6), interferon (IFN) gamma, tumor necrosis factor-alpha (TNF-alpha) and colony
      stimulating factors (particularly GM-CSF). Moreover, mycoplasmas are potent
      inductors of cytokine secretion by fibroblasts in culture. Since growth factors
      are determinants for the activation and proliferation of immunocompetent cells in
      vitro, we decided to investigate if these effects are concordant with the finding
      of mycoplasma contamination. In order to address this question, we compared the
      pattern of lymphokine secretion by normal-derived human fibroblasts in culture
      with and without Mycoplasma spp. contamination. We found those human fibroblasts
      that have been contaminated with mycoplasma show production of IL-13 at the
      transcriptional level. This effect coincides with discrete morphological changes
      as compared to uncontaminated human fibroblasts. This is the first report to
      acknowledge that mycoplasma contamination can induce mRNA expression for IL-13 in
      cultured human fibroblasts.

PMID- 8880138
TI  - Detection of peptidoglycan and beta-glucan with silkworm larvae plasma test.
AB  - A method to detect peptidoglycan and (1-->3) beta-D-glucan with silkworm larvae
      plasma (SLP) derived from the hemolymph of the silkworm, Bombyx mori was
      developed. SLP contains all of the factors of the pro-phenol oxidase cascade, an
      important self-defense mechanism of insects. Peptidoglycan or (1-->3)-beta-D
      glucan initiates the cascade, in which pro-phenol oxidase is finally activated to
      phenol oxidase. The phenol oxidase activity was colorimetrically or visually
      detected with 3,4-dihydroxyphenylalanine as a substrate. SLP displayed high
      reactivity with peptidoglycan and polysaccharides containing 1,3-beta-glucosidic
      linkages, but not with endotoxins. SLP is useful for the detection of microbial
      contamination because peptidoglycan and (1-->3)-beta-D-glucan are cell wall
      components of bacteria and fungi, respectively.

PMID- 8880139
TI  - Adherence of Mycoplasma pneumoniae to human alveolar macrophages.
AB  - The human pathogen Mycoplasma pneumoniac causes primary atypical-cold agglutinin
      positive pneumonia. Since alveolar macrophages internalize mycoplasma as part of
      their immune defense, we studied characteristics of the human macrophage receptor
      for opsonized and nonopsonized M. pneumoniae. The glass-adhering subpopulation of
      M. pneumoniae attached more than the non-adherent subpopulation. The attachment
      was dose-dependent and enhanced by opsonization in the presence of human serum.
      It is inhibited by sulfated compounds such as dextran-sulfate and
      polyanetholsulfonic acid, but not by dextran or several monosaccharides,
      suggesting that sulfated glycolipids on the macrophage surface may act as
      receptors for M. pneumoniae binding. In addition, sialylated compounds, such as
      fetuin and alpha 1-acid glycoprotein, were found to be potent inhibitors of the
      attachment, also indicating the role of sialic acid residue in recognition and
      attachment of M. pneumoniae to human alveolar macrophages.

PMID- 8880141
TI  - Treatment of HeLa cells with bacterial water extracts inhibits Shigella flexneri
      invasion.
AB  - Pathogenesis mediated by Shigella flexneri requires invasion of the
      gastrointestinal epithelium. It has been previously shown that HeLa cells
      challenged with S. flexneri show alterations in their phosphotyrosine-containing
      protein profile. In this report, we demonstrated that bacterial water extracts
      (WE) abrogated the invasion of HeLa cells by S. flexneri in a dose-dependent
      manner. A proteinaceous component of S. flexneri was shown to be responsible for
      this inhibitory activity. Proteins encoded on the 140-MDa plasmid were not
      responsible for the observed inhibition. WE from other Gram-negative bacteria
      also inhibited Shigella invasion of HeLa cells pretreated with WE showed changes
      in the profile and the intensity of phosphotyrosine-containing protein bands.
      These data were consistent with a surface protein component in WE which initiated
      aberrant host cell signaling at the membrane which may account for the inhibition
      of bacterial entry.

PMID- 8880140
TI  - Electrophoretic mobility and immune response of outer membrane proteins of Vibrio
      cholerae O139.
AB  - The outer membrane (OM) protein components of a Vibrio cholerae O1 and four V.
      cholerae O139 strains, collected from cholera patients, were analysed by SDS
      PAGE. A protein of 69 kDa molecular mass was observed only when the OMPs were
      prepared from strains grown in synthetic broth. As a result of passage in the
      rabbit ileal loop (RIL), virulence was enhanced, and a protein component around
      18 kDa of the V. cholerae O139 OM became the major protein component. On
      immunoblot analysis with rabbit antiserum against V. cholerae O139 OM, it was
      shown that, apart from the major protein component of V. cholerae O1 OM of around
      45 kDa and that of V. cholerae O139 OM of around 38 kDa, all other minor protein
      components were cross-reactive between the two serogroups. In immunoblot assays
      with convalescent sera obtained from V. cholerae O139-infected patients, it was
      observed that in addition to the lipopolysaccharide (LPS)-induced antibody, only
      the 38 kDa major protein component elicited considerable levels of antibody in
      the patient. Minor OM components of 18 kDa were detected in the immunoblot
      analysis by LPS-directed antibody, however, as the OM proteins are known to be
      associated with LPS.

PMID- 8880142
TI  - Human immune response to epitopes on the meningococcal outer membrane class 5
      protein following natural infection.
AB  - Two monoclonal antibodies (mAbs) were produced against a serogroup B Neisseria
      meningitidis strain. These mAbs recognized two epitopes in the class 5 outer
      membrane proteins (OMP), designated P5.7 and P5.Bm, and were able to kill the
      homologous strain through complement activation. Both epitopes were surface
      exposed and 68% of group B meningococcal clinical isolates had one or both
      epitopes present in their class 5 OMP. Antibodies to one or both epitopes were
      demonstrated in 17 patients with meningococcal meningitis using an ELISA
      inhibition assay. Of the 17 paired sera, 41% and 29% of the acute-phase sera had
      antibodies to the P5.7 and P5.Bm epitopes, respectively. Immunoglobulin G to
      P5.Bm were found in all 17 convalescent-phase sera while specific antibodies
      against P5.7 were only found in 6 of these sera. These results demonstrate the
      potential importance of the P5.Bm and P5.7 epitopes on the class 5 OMP as
      candidates for vaccine composition.

PMID- 8880144
TI  - Suppression of mitogen-induced lymphocyte proliferation by syringomycin-E.
AB  - Syringomycin E (SR-E) is a low molecular weight bacterial lipodepsipeptide with
      antifungal properties. Owing to immunosuppressive activities of such compounds as
      cyclosporine, FK506 and rapamycin, we studied the effect of SR-E on proliferation
      of human blood lymphocytes in vitro. SR-E, by itself, had no effect but the
      mitogen-induced lymphocyte proliferation was significantly suppressed. The
      suppressive effect was more pronounced with pokeweed mitogen (PWM) as compared to
      phytohemagglutinin (PHA) or monoclonal antibody to CD3 (anti-CD3). Since these
      mitogens induce cellular immunity (T cell-dependent), SR-E may potentially be a
      novel immunosuppressive compound.

PMID- 8880143
TI  - Absence of involvement of nitric oxide in LP-BM5-induced immunodeficiency
      syndrome.
AB  - To examine the role of nitric oxide (NO) in murine AIDS (MAIDS) pathogenesis, we
      determined NO production and inducible NOS (iNOS) mRNA expression in the
      macrophages of LP-BM5-infected mice, together with the in vivo effects of L-NAME,
      a competitive inhibitor of NO synthase. LP-BM5 infection induced neither
      spontaneous nitrite production nor iNOS mRNA expression. No differences in IFN
      gamma + LPS-induced nitrite production or iNOS mRNA expression were observed in
      macrophages, from non-infected or infected mice. Spleen weight, ecotropic MuLV
      replication, the blood lymphocyte phenotype and proliferative response of
      splenocytes were not modified by L-NAME. LP-BM5 infection did not increase
      macrophage NO production and NO production did not appear to protect against LP
      BM5-induced immunodeficiency.

PMID- 8880145
TI  - The construction of novel mobilizable YAC plasmids and their behavior during
      trans-kingdom conjugation between bacteria and yeasts.
AB  - Trans-kingdom conjugation is an easy and efficient method for gene transfer from
      prokaryotes to eukaryotes since it does not require DNA extraction and
      purification. We constructed novel mobilizable plasmids pAY-YAC-B and pAY-YAC-E.
      The origin of conjugal transfer (oriT) was inserted at two different positions,
      pAY-YAC-B contains oriT region in between two telomeres whereas pAY-YAC-E has
      oriT at the cloning site of pYAC4. By conjugation, both plasmids were
      successfully transferred from E. coli to S. cerevisiae and S. kluyveri yeasts
      with the aid of helper plasmid pRH220 which harbors mob and tra genes. The
      plasmids were transferred more efficiently in S. cerevisiae compared to S.
      kluyveri. The analyses by restriction enzyme digestion and Southern hybridization
      indicated that both plasmids maintained their original structure and size in
      transconjugant yeasts, therefore, reflecting the faithful nicking and subsequent
      resealing of plasmids during conjugation. The comparison between conjugative
      transfer and transformation has also been performed and discussed.

PMID- 8880146
TI  - Retrofitting high molecular weight DNA cloned in P1: introduction of reporter
      genes, markers selectable in mammalian cells and generation of nested deletions.
AB  - The bacteriophage P.1. cloning system is proving to be quite useful for the
      cloning and analysis of genomic DNA inserts of up to 95 kb in size. In an effort
      to use that DNA directly in biological experiments we have embarked on a scheme
      to retrofit the P.1. DNA using a mini-Tn10 transposon system. This transposon
      system is used in two ways: (i) to introduce a variety of sequence signals that
      are recognizable in mammalian cells, such as mammalian cell-responsive resistance
      markers and reporter genes, and (ii) to generate a nested set of deletions in a
      P.1. clone by using a ioxP site located within the transposon. In this report we
      show that such transpositions into P.1. DNA are efficient, distributed throughout
      the entire length of the genomic fragment and do not disrupt the DNA in any
      location other than the site of insertion of the transposon. The Tn10-based P.1.
      transduction system described here provides a general scheme for retrofitting any
      large genomic DNA cloned in a P.1. vector, thus facilitating the use of clones
      from the current P.1. recombinant libraries in cellular transformation studies.

PMID- 8880147
TI  - A novel mutation in the MITF gene causes Waardenburg syndrome type 2.
AB  - Mutations in the MITF gene on human chromosome 3 have been reported in families
      with Waardenburg Syndrome Type 2 (WS2), an autosomal dominant disorder
      responsible for a large proportion of congenital hearing loss. We examined 16
      families with WS2 for mutations in the MITF gene. In one four-generation family,
      we found a novel two-base deletion in exon 6 of the MITF gene at nucleotide
      position 699. This mutation introduces a frame-shift and stop codon which leads
      to a truncation of the protein. This mutation is predicted to have phenotypic
      consequences not withstanding evidence of reduced penetrance and heterogeneity
      within the family studied.

PMID- 8880148
TI  - Isolation of genes encoding tRNA binding proteins by probing an expression
      library with unmodified tRNA.
AB  - A rapid method for isolating Escherichia coli genes encoding proteins which bind
      unmodified, but not modified, tRNA is described. The method is generally
      applicable, and can be used to clone many RNA binding proteins where a structured
      RNA ligand is known.

PMID- 8880149
TI  - Subtractive hybridization, a technique for extraction of DNA sequences
      distinguishing two closely related genomes: critical analysis.
AB  - The present status of genomic DNA subtraction techniques is reviewed. The
      advantages and disadvantages of the widely-used methods of genome subtraction are
      discussed. Using the kinetic model of subtractive hybridization developed by us
      previously (Sverdlov and Ermolaeva, 1993; Sverdlov and Ermolaeva, 1994), the
      application of genome subtraction to various problems is analyzed. It is
      concluded that the technique should be further advanced based on subtraction of
      single-stranded DNAs. This strategy would enable one to efficiently extract
      target sequences omitting the stage of genome simplification.

PMID- 8880150
TI  - The frequency distribution of blood-flow velocities in the extraocular vessels.
AB  - PURPOSE: The study was carried out in order to assess the distribution of normal
      values of the blood-flow velocity in the extraocular vessels. METHODS: In 240
      healthy visitors to a public fair, blood-flow characteristics in the extraocular
      vessels were measured, and the resistivity index was calculated. Blood-flow
      velocity was measured with a color Doppler imaging device, using a 7.5-mHz linear
      array transducer. Peak-systolic and end-diastolic blood-flow velocities in the
      arteries were measured, and the resistivity index was calculated. In the central
      retinal vein the minimal and maximal blood-flow velocities were measured. The
      statistical analysis of the 14 measured and calculated variables included
      descriptive statistics, frequency distribution, and quantile plots. RESULTS: The
      quantile plots of the cumulative frequency showed that none of these 14 variables
      are normally distributed. Also, no normal distribution could be achieved by
      adjustment of the data by age. CONCLUSIONS: The blood-flow velocities in the
      extraocular vessels measured are not distributed normally. Therefore,
      nonparametric tests are to be used for statistical analysis if the sample size is
      small. The estimation of tolerance intervals has to be based on distribution-free
      assumptions.

PMID- 8880151
TI  - Electrical conductivity of tear fluid in healthy persons and keratoconjunctivitis
      sicca patients measured by a flexible conductimetric sensor.
AB  - BACKGROUND: It is known that the osmolarity of tears increases in
      keratoconjunctivitis sicca (KCS) patients and therefore could be a sensitive and
      specific indicator for the diagnosis of KCS. However, owing to the difficulties
      in using the current methods of tear fluid measurement these procedures have not
      been employed in clinical practice. A newly devised flexible conductimetric
      sensor fabricated using microelectronic techniques is small and flexible enough
      to be placed on the ocular surface to measure the electrical conductivity can be
      considered as an indirect function of electrolyte activity, or osmolarity.
      Therefore, we applied this new sensor to measure the tear fluid conductivity in
      KCS patients and healthy volunteers. METHODS: A flexible conductimetric sensor,
      consisting of a hydrophilic polytetrafluoroethylene membrane placed between two
      gold-coated layers, was placed directly into the temporal conjunctival cul-de
      sac. The tear fluid conductivity was monitored graphically on a computer display.
      The sodium chloride concentration of tear fluids was calculated from the
      calibration curve and converted to the equivalent electrolyte concentration.
      RESULTS: The electrolyte concentrations were 324.8 +/- 41.0 mEq/1 in KCS patients
      (29 samples obtained from 16 KCS patients) and 296.4 +/- 30.1 mEq/1 in healthy
      persons (33 samples obtained from 17 healthy persons). The difference was
      significant (P < 0.01). A positive correlation was found between the electrolyte
      concentrations in KCS and the rose bengal score (coefficient = 0.36). CONCLUSION:
      The tear fluid conductivity in healthy persons and KCS patients could be
      monitored without ocular damage, and the measured values were consistent with
      previous reports. This method will be a new diagnostic tool for detecting tear
      abnormalities.

PMID- 8880152
TI  - Immunological profiles in patients with acute retinal necrosis.
AB  - PURPOSE: Acute retinal necrosis (ARN) is a newly recognized disease caused by
      human commensal viruses of the herpes family (herpes simplex virus, varicella
      zoster virus and cytomegalovirus) occurring in apparently immunocompetent
      patients. As at least three viruses can cause ARN, the modification in the host
      virus interaction at the origin of the disease most probably comes from the host.
      A review of 216 reported cases of ARN showed that there were signs of impaired
      cellular immunity in 16% of these cases. The purpose of this study was to
      investigate immune parameters in ARN. METHODS: In nine HIV-negative ARN patients
      who were not under steroid or immunosuppressive therapy, the following
      prospective immunological investigations were performed: (1) skin testing for
      delayed-type hypersensitivity to seven common antigens (Candida, diphtheria,
      purified protein derivative tuberculin Proteus, Streptococcus, tetanus,
      Trichophyton); (2) lymphocytic proliferative responses in vitro to these antigens
      and to three mitogens; (3) determination of blood lymphocyte sub-populations by
      flow cytometry. RESULTS: Cutaneous anergy was found in five of seven tested
      cases. The lymphocyte proliferative index was less than 20% of the index of a
      control group for all antigens in three of nine cases, and for three or more
      antigens in eight of nine cases. In eight of nine cases there was a relative
      increase of B-lymphocytes, and in seven of nine cases B-lymphocytes were also
      increased in absolute numbers. In all nine cases one or more of these parameters
      were abnormal. CONCLUSION: Our findings suggest that ARN may develop in
      association with an imbalance of the immune system characterized by an impaired
      cellular response and/or a maintained or increased humoral response.

PMID- 8880153
TI  - Motion discrimination of single targets: comparison of preliminary findings in
      normal subjects and patients with glaucoma.
AB  - BACKGROUND: Luminance, global motion and flicker sensitivities are affected in
      patients with primary open-angle glaucoma. Although no theoretical model has been
      put forward to explain the observed reduction in sensitivity in this patient
      group, these findings have often been attributed to diffuse and selective loss of
      large optic nerve fibres. METHODS: Movement processing was investigated using an
      optical projection system that generates smooth, continuous motion with control
      of speed, displacement and motion direction. Motion-displacement and direction
      discrimination thresholds were measured in eight normal subjects and in three
      patients with diagnosed glaucoma. At each speed tested, targets were presented
      for a range of displacements and thresholds were extracted after probit analysis.
      The measurements were carried out both foveally and at 19 degrees in the
      periphery and provided the data necessary to develop and optimise a model of
      motion perception based on multiple time delays for the correlation of signals
      that map progressively more distant parts of the visual field. RESULTS: Our
      preliminary findings show that direction discrimination can be at chance level
      even for large displacements when motion is detected 80% of the time. Model
      simulations show that specific changes in the spatial sampling interval and the
      speed of transmission of the motion signals involved can cause the observed
      reduction in motion sensitivity and direction discrimination in patients with
      glaucoma. CONCLUSIONS: A model for motion detection and direction discrimination
      of single targets has been proposed to account for the measured functional
      relationship between motion displacement thresholds and target speed in normal
      subjects. Tested patients with glaucoma show reduced motion sensitivity and poor
      discrimination of motion direction. The type of degraded performance observed
      experimentally in glaucoma patients is also predicted by the model. Such
      predictions require specific changes in model parameters that may be indicative
      of changes in the retina caused by the disease.

PMID- 8880154
TI  - Primary vitrectomy without scleral buckling for rhegmatogenous retinal
      detachment.
AB  - BACKGROUND: Pars planta vitrectomy has evolved as an alternative method in the
      treatment of more complicated rhegmatogenous retinal detachments. We report a
      series of patients who underwent primary vitrectomy with gas tamponade without
      the use of additional scleral buckling. METHODS: A retrospective study of 53
      patients with a follow-up of 6-45 months (mean 17.8 months) was carried out.
      Preoperative findings included unusual, multiple or large breaks, vitreous
      haemorrhage, proliferative vitreoretinopathy and bullous retinal detachment.
      Preoperative visual acuity was between light perception and 1.0, with 30% (16/53)
      of patients with 0.4 or better. RESULTS: Retinal reattachment was achieved in 64%
      of cases (34/53) with one and in 92% (49/53) with one or more operations. Final
      visual acuity was between light perception and 1.0, with 41% (22/53) of patients
      with 0.4 or better. Cataract formation occurred in 86% (37/43) of all patients
      with a clear lens preoperatively. Macular pucker was noted in 11% (6/53) and
      postoperative proliferative vitreoretinopathy causing redetachment in 6% (3/53).
      CONCLUSION: With primary vitrectomy, a high final anatomical success rate with
      few intraoperative complications can be achieved in more complicated forms of
      rhegmatogenous retinal detachment. The major drawback of the procedure is the
      high incidence of post-operative cataract formation.

PMID- 8880155
TI  - Malignant melanoma of the conjunctiva: occurrence and survival following surgery
      and radiotherapy in a Danish population.
AB  - PURPOSE: To describe patient characteristics, risk of recurrence, and survival in
      patients with premalignant and malignant melanocytic lesions of the conjunctiva.
      METHODS: In a retrospective study, 55 cases with a minimum follow-up of 10 years
      were reviewed. RESULTS: The actuarial 5-and 10-year survival rates were 86% (95%
      Cl: 76-96%) and 73% (95% Cl: 60-87%) respectively. The 5-year risk of local
      recurrence was 35% (95% Cl: 21-49%), and the 10-year risk was 43% (95% Cl: 28
      58%). Primary acquired melanosis with atypia was the first manifestation in 13
      cases, malignant melanoma in 42 cases. No significant difference in survival and
      recurrence was found between the two groups or by gender, location of primary
      lesion, histological characteristics, or extent of surgical procedure. A minimum
      incidence of 0.052 cases a year per 100 000 in Denmark was calculated.
      CONCLUSION: The results are estimated to represent a nationwide sample of
      patients. No prognostic factors of significance were identified.

PMID- 8880156
TI  - Pituitary adenylate cyclase-activating peptide-immunoreactive nerve fibers in the
      cat eye.
AB  - PURPOSE: To study the occurrence and distribution of the neuropeptide pituitary
      adenylate cyclase-activating peptide (PACAP) in ocular and orbital structures of
      the cat. METHODS: Immunocyto-chemistry to localize PACAP and double
      immunostaining to detect co-localization of PACAP with other neuropeptides.
      RESULTS: Numerous PACAP-immunoreactive nerve fibers were observed in the lacrimal
      gland, choroid and retroocular arteries. There was a sparse supply of PACAP
      containing nerve fibers in the iris, ciliary body and conjunctiva. Subpopulations
      of PACAP-containing nerve fibers stored vasoactive intestinal peptide (VIP) or
      calcitonin gene-related peptide (CGRP). Around 10% of the ganglion cells in the
      sphenopalatine ganglion harbored PACAP immunoreactivity. In the trigeminal
      ganglion around 5% of the neuronal cell bodies and in the ciliary ganglion only
      occasional ganglion cells contained PACAP immunoreactivity. PACAP
      immunoreactivity co-localized with VIP in the sphenopalatine ganglion and with
      CGRP in the trigeminal ganglion. CONCLUSION: PACAP-containing nerves in the eye
      and associated structures demonstrate a distribution pattern resembling that of
      VIP. Subpopulations of nerve fibers containing PACAP immunoreactivity store VIP
      or CGRP immunoreactivity. Neuronal PACAP in the eye and orbit may take part in
      regulation of smooth muscle tone, glandular secretion and sensory processing.

PMID- 8880157
TI  - Course of the optic nerve fibers through the lamina cibrosa in human eyes.
AB  - BACKGROUND: This study investigated whether regional variations in the course of
      the optic nerve fibers through the lamina cribrosa may be one of the reasons why
      the local susceptibility for glaucomatous optic nerve fiber loss differs among
      the various regions of the optic disc. METHODS: The study included 34 human eyes
      enucleated because of a malignant melanoma of the peripheral choroid without
      involvement of the anterior chamber angle or the optic nerve. Anterior-posterior
      sections through the pupil and the optic disc were histomorphometrically
      evaluated. In the central region and the peripheral part of the optic disc, we
      measured the thickness of the lamina cribrosa and the length of the lamina
      cribrosa "channels" through which the nerve fibers pass. RESULTS: In the
      peripheral parts of the disc, compared with its central region, the lamina
      cribrosa was significantly thicker (P < 0.0001, Wilcoxon test), the lamina
      cribrosa "channels" with the nerve fibers passing through were significantly
      longer (P < 0.0001), and the ratio of length of the fiber "channels" to the
      thickness of the lamina cibrosa was significantly higher (P = 0.0001).
      CONCLUSION: The lamina cribrosa is thicker and the course of the optic nerve
      fibers through the lamina cribrosa is more curvilinear in the disc pheriphery
      than in the disc center. These variations in the anatomy of the lamina cribrosa
      may be one of several factors influencing the regional susceptibility for
      glaucomatous optic nerve fiber loss within the optic nerve head.

PMID- 8880158
TI  - Immunosuppressive effect of bovine seminal ribonuclease on a model of corneal
      transplantation in rabbit.
AB  - BACKGROUND: Bovine seminal ribonuclease (BS RNase) was determined to have a
      specific suppressive effect on the proliferation of T lymphocytes in vitro. Its
      immunosuppressive effect was proven in skin grafting in mice as well. METHODS:
      The immunosuppressive effect of BS RNase was evaluated in tissue cultures and on
      a model of corneal transplantation in rabbits. The penetration of BS RNase into
      the anterior chamber was detected by immunoblotting of anterior chamber fluid
      obtained from animals treated either topically or subconjunctivally. RESULTS: In
      vitro blastic transformation of mouse T lymphocytes was significantly inhibited
      by BS RNase (concentrations 15-250 micrograms/ml). No such effect was observed on
      B lymphocytes. In the rabbit model of corneal graft rejection, BS RNase injected
      subconjunctivally prolonged mean graft survival time significantly (33.4 days)
      compared with placebo (salt solution; MST 17.7 days). No BS RNase was detected by
      immunoblotting in anterior chamber fluid after either topical or subconjunctival
      application. CONCLUSION: BS RNase showed significant immunosuppressive effect
      both in the blastic transformation test and in the rabbit high-risk model of
      corneal transplantation. Negative results of anterior chamber fluid
      immunoblotting indicate poor absorption of the drug.

PMID- 8880160
TI  - Sex differences in bone growth of broiler chickens.
AB  - Females are often supposed to have a lighter skeleton than males, even in avian
      domestic species. However, in broiler chickens, females are less susceptible to
      bone deformities than males. In order to better understand these conflicting
      facts, male and female broilers were compared for the growth of cortical bone.
      Morphology, histomorphometry, composition and biomechanical properties of the
      tibiotarsi were analysed in both sexes at 1, 12, 26 and 42 days of age. The
      quantity of bone tissue of the tibiotarsus (weight, volume, diameter of the
      diaphysis, area of the cortex) was smaller in females, although the occurrence of
      varus-valgus deformations of the intertarsal joint was largely reduced in female
      chickens (8.8% versus 19.9% in males at 42 days of age). The tibia became
      significantly lighter in females from 26 d of age. Differences in tibia length
      and volume became significant at 42 d of age only, while cross-sections of the
      diaphysis were smaller in females from the hatching, leading to thinner bones in
      females. The percentage of dry matter of tibiae was higher in females from
      hatching. From 12 days old, tibiotarsi of females tended to be less porous and
      were more mineralized (higher ash/dry matter ratio). In females, mineralization
      proceeded at a higher rate (MAR) until 26 d of age and MAR became higher in males
      afterwards. The stiffness of the tibia diaphysis was similar in males and females
      all along the growth. In conclusion, the growth of cortical bone is very
      different in male and female broilers. In female broilers, the thinness of bone
      diaphysis is counter-balanced by modifications in the composition of the matrix
      and in the porosity of the cortex, leading to equal biomechanical characteristics
      of tibiotarsi in both sexes.

PMID- 8880159
TI  - Chronic basidiomycetous endophthalmitis after extracapsular cataract extraction
      and intraocular lens implantation.
AB  - BACKGROUND: Basidiomycetes are known as rare pathogens for meningitis, sinusitis,
      pneumonia, ulcerative lesions of the hard palate and onychomycosis. To our
      knowledge, no filamentous basidiomycete has been reported from a case of fungal
      endophthalmitis. PATIENT: We report on a 67-year-old man with delayed-onset
      endophthalmitis caused by an opportunistic basidiomycete. Tissue obtained during
      vitrectomy was cultured and examined by light and transmission electron
      microscopy. After enucleation the eye was examined by light microscopy.
      CONCLUSION: The patient had endophthalmitis from a sterile hyphomycete, harboured
      in remnants of lens capsule and a granuloma on the ciliary body. It was
      recognized as a Holobasidiomycete on the basis of its dolipore structure with
      perforated pore cap, seen with transmission electron microscopy. Species
      identification was not possible because fruiting bodies were absent. The patient
      failed to respond to intravitreal and systemic amphotericin B and systemic
      itraconazole. The eye was enucleated. This case demonstrates that filamentous
      basidiomycetes can cause endophthalmitis when inoculated during cataract
      extraction.

PMID- 8880161
TI  - Weight gain by middle-aged mice: dietary modification does not result in loss.
AB  - Dietary induced obesity susceptibility and persistence was examined in middle
      aged female retired C57BL/6J breeder mice. One year old mice were fed control
      chow (C), chow with added corn oil (O), or chow with added sweetened condensed
      milk (SCM) for 18 weeks, during which time food consumption and weight change
      were monitored. Mice in both the O and SCM groups gained significantly more
      weight than the C group. Weight increase correlated with caloric intake for the O
      and SCM groups. All mice were then fed standard laboratory chow for 22 weeks. The
      increased weight of both supplemented groups was maintained during this time
      suggesting that caloric intake is not the sole variable controlling weight
      maintenance in adult female mice. We encourage the use of older mice as a model
      to explore means of manipulating adult weight in humans.

PMID- 8880162
TI  - A simple but flexible growth function.
AB  - The functional form W(t) = Wf - (Wf - Wo) exp[-k infinite (t - T) + 2c(root of t 
      root of T)] where Wf, Wo, k infinite, c and T are constants, is derived as a
      growth equation and evaluated using commonly applied growth functions such as the
      Gompertz, logistic, monomolecular and Richards. Further evaluation is made with
      reference to sets of observations on growth in a number of animal species ranging
      from mice to horses. The new function provides a flexible growth equation capable
      of describing sigmoidal and diminishing returns behaviour. It appears adept at
      describing sigmoidal patterns exhibiting faster early growth and a fairly low but
      variable point of inflexion, and can therefore be perceived as a generalised
      Gompertz equation. The function also has the ability to describe a wide range of
      hyperbolic shapes when there is no point of inflexion. The analysis described
      suggests that this simple equation is a worthwhile addition to the corpus of
      growth functions.

PMID- 8880163
TI  - Morphometric analysis of gastrocnemius muscle fiber size and fiber proportions in
      the hypophysectomized rat after prolonged administration of growth hormone or
      thyroxine.
AB  - This study investigated the effects of either growth hormone or thyroxine on
      muscle fiber atrophy caused by hypophysectomy in male Wistar rats. Muscle fiber
      size is reported as equivalent circle diameter (ECD) in transverse section of
      fresh-frozen gastrocnemius muscle. Three months post-hypophysectomy type 1 (slow
      twitch) and type 2 (fast twitch) muscle fibers were smaller (p < 0.01) than those
      in intact controls as shown previously in this laboratory. The administration of
      human growth hormone (GH) (50mIU/100g body weight/day) to hypophysectomized
      (hypox) rats for 42 days, stimulated body growth, restored 42% of the lost
      gastrocnemius muscle weight (p < 0.05) and 36% of the lost type 1 fiber size, (p
      < 0.01), but had no effect on type 2 fiber size. Treatment of hypox rats with
      physiological doses of thyroxine (5 micrograms T4/100g body weight/alternate day)
      for 42 days did not affect body growth, gastrocnemius muscle weight or type 1
      fiber size, but reduced the size of type 2 fibers (p < 0.01). Thyroxine prevented
      the decline in the percentage of type 2 fibers which occurs after hypophysectomy.
      This unique observation suggests that thyroid hormone regulates the proportion of
      different fiber types in the gastrocnemius muscle. Thus, in hypox rats, GH
      promoted growth of type 1 or slow twitch muscle fibers needed to support the
      increasing weight of the growing body. Physiological doses of T4 did not
      stimulate growth, but caused further atrophy of of type 2 fibers possibly while
      providing fuel for rapid movement.

PMID- 8880164
TI  - Incremental changes in total and regional body composition of growing pigs
      measured by dual-energy x-ray absorptiometry.
AB  - The pig was used as a model for the application of dual-energy x-ray
      absorptiometry (DXA) for measuring changes in total and regional body composition
      that accompany body growth. Ten pigs were scanned at the beginning of the study
      (26.3 +/- 8.2 kg) and at 14 day intervals until reaching a final weight of 88.6
      +/- 2.3 kg. Final body composition was validated by chemical analysis of the
      carcass. DXA fat and lean tissue measurements were corrected by using values
      based on previous calibration studies. From individual growth curves, rates of
      fat (295 +/- 50 g/d), lean (531 +/- 50 g/d) and bone mineral (16.7 +/- 1.4 g/d)
      deposition rates were estimated. Furthermore, using regional analysis these
      tissue deposition rates partitioned into front legs, back legs and body trunk.
      The final DXA measurements of 87.5 kg for total tissue mass, 27.9% for percent
      body fat and 24.4 kg for total fat mass were not significantly different (P >
      .05) from direct or chemical measurements. The DXA measurement of bone mineral
      content 1912 g (2.18%) was similar to the estimate based on total body ash, 1980
      g (2.23%). Also, from the final DXA values for lean tissue mass, it was predicted
      that the body contained 13.5 kg or 15.4% protein and 45.74 kg or 52.3% water.
      These results indicate that DXA could be an appropriate method for studies
      involving sequential measurements of body composition during growth.

PMID- 8880165
TI  - Outcome measurement in economic evaluation.

PMID- 8880166
TI  - Confidence intervals for cost-effectiveness ratios: an application of Fieller's
      theorem.
AB  - Application of cost-effectiveness analysis (CEA) is growing rapidly in health
      care. Two general approaches to analysis are differentiated by the type of data
      available: (i) deterministic models based upon secondary analysis of
      retrospective data from one or more trials and other sources; and (ii) stochastic
      analyses in which the design of a randomized controlled trial is adapted to
      collect prospectively patient-specific data on costs and effectiveness. An
      important methodological difference between these two approaches is in how
      uncertainty is handled. Deterministic CEA models typically rely upon sensitivity
      analysis to determine the robustness of findings to alternative assumptions,
      whereas stochastic (CEA) analysis, as part of prospective studies, permits the
      use of conventional statistical methods on the cost and effectiveness data for
      both inference (hypothesis testing) and estimation. This paper presents a
      procedure for the statistical analysis of cost-effectiveness data, with specific
      application to those studies for which effectiveness is measured as a binary
      outcome. Specifically, Fieller's Theorem was used to calculate confidence
      intervals for ratios of the two random variables of between-treatment differences
      in observed costs and effectiveness, i.e. the incremental cost-effectiveness
      ratio.

PMID- 8880167
TI  - The cost-effectiveness of diagnostic strategies in patients with suspected
      pulmonary embolism.
AB  - The cost-effectiveness of various diagnostic strategies in patients with
      clinically suspected pulmonary embolism (PE) was analysed using a modelling
      approach. In 451 consecutive patients with clinically suspected PE data on the
      performance of diagnostic tests were collected prospectively in two large
      teaching hospitals in Amsterdam, The Netherlands. The ventilation-perfusion lung
      scan was used as the primary diagnostic test in all patients. In patients with a
      non-diagnostic lung scan result the performance of a clinical decision rule, a D
      dimer test, and ultrasonography of the leg veins was evaluated with pulmonary
      angiography as the gold standard. It was estimated that the strategy recommended
      by a 1992 Dutch consensus meeting costs about Dfl 4400 per patient and that
      97.02% of the patients can be expected to survive the first 6 months after the
      primary PE. The nation-wide annual costs for the diagnosis and treatment of
      patients by this strategy were estimated at 163 million Dutch Guilders.
      Subsequently, the costs and effects of alternative strategies were evaluated in a
      modelling approach, and compared with those of the consensus strategy. One
      strategy was selected that produces the best results in terms of survival and
      leads to considerable savings as compared with the consensus strategy. In this
      strategy subsequently a ventilation-perfusion scan, a clinical decision rule, a D
      dimer test, a pulmonary angiography and leg ultrasonography are performed.
      Patients with a high probability ventilation-perfusion scan, an abnormal
      angiography or leg ultrasound test are treated, whereas treatment is withheld in
      patients with a normal ventilation-perfusion scan, a normal clinical decision
      rule, a negative D-dimer test, a normal angiography, or a normal leg ultrasound
      test. This strategy will have to prove its value and usefulness in clinical
      practice in a subsequent prospective validation phase.

PMID- 8880168
TI  - Cost-effectiveness of antenatal anti-D prophylaxis.
AB  - This paper estimates the incremental cost-effectiveness of providing antenatal
      anti-D prophylaxis in varying dose sizes to either primigravidae or all Rh D
      negative women. It presents a model for calculating the net cost per 1000 'at
      risk' women based on the costs of anti-D prophylaxis and the future NHS costs
      avoided. Incremental cost-effectiveness is measured in terms of the net cost per
      Rh D-alloimmunization and the net cost per Rh HD loss prevented. Programmes for
      Rh D negative primigravidae are more cost-effective than the same dose protocol
      extended to all Rh D negative women. The 1 x 1250 iu programme is the most cost
      effective option.

PMID- 8880169
TI  - The discounting of lives saved in future generations--some empirical results.
AB  - The aim of this note is to estimate the discount rates that individuals in the
      present generation in Sweden use to discount lives saved in future generations at
      different points in time. A binary survey question, where individuals choose
      between saving lives in their own generation versus saving lives in future
      generations, was administered in a general population sample of 850 individuals.
      Three time horizons of 20, 50 and 100 years were used in three different
      subsamples. Logistic regression analysis was used to estimate the discount rate.
      The estimated annual discount rate is 25% for the 20 year time horizon, 12% for
      the 50 year time horizon and 8% for the 100 year time horizon.

PMID- 8880171
TI  - NHS contracts: an agency approach.
AB  - The White Paper Working for Patients has produced dramatic changes in the
      organization of health care in the UK that will soon be followed by analogous
      reforms in other countries. The core of the reform is represented by the
      separation of the responsibility for purchasing health care from providing the
      services. The creation of this internal market is said to enhance efficiency, but
      some peculiar characteristics of health care prevent a Pareto optimal solution
      being reached. This paper describes the purchaser-provider relationship using an
      innovative principal agent model to assess the relative merits of the different
      forms of contracts. The model is also used to show how competition among
      providers allows the purchaser to extract this private information. From a
      theoretical point of view, the approach is innovative in the formulation of the
      principal's objective function; the interesting finding is that the presence of a
      stringent budget constraint alters both risk-sharing conditions and the First
      best contract proposed by the literature. From a policy point of view, the paper
      explains why in the first wave over 75% of contracts between purchasers and
      providers were block contracts. It is also demonstrated why this contractual form
      should be avoided.

PMID- 8880170
TI  - Household characteristics affecting where mothers deliver in rural Kenya.
AB  - Data from a household survey were used to analyse the distribution of newborn
      deliveries in a rural area of Kenya. It was found that 52% of deliveries occurred
      at home or with traditional birth attendants. Using regression techniques, the
      most significant predictors of choosing an informal delivery setting are the
      household's distance from the nearest maternity bed and whether a household
      member has insurance. The results suggest that travel time is an important
      barrier to access. Therefore, quality improvements at existing facilities may not
      result in greater use of modern sector delivery, particularly if improvements are
      partially offset by user fees.

PMID- 8880172
TI  - Contracting in the NHS quasi-market.
AB  - This paper examines the development of contracting within the NHS on the basis of
      the data collected as part of a national survey of English District Health
      Authorities carried out in late 1994. The paper starts with a discussion of the
      background to contracting and its evolution during the first 4 years of the NHS
      internal market. The second section describes the methodology employed in the
      national survey. The third section presents the results of the survey alongside a
      discussion of their relevance in terms of the economics of contracting. This
      section shows the prevalence of different types of contracts and discusses the
      emergence of the most common type-sophisticated block contracts. Details are
      provided of how contracts deal with issues such as the measurement of activity,
      the pricing of projected activity and of activity variances (mainly at marginal
      cost), as well as the involvement of clinicians in contracting. Other topics
      explored include the management of extra contractual referrals, contracting for
      specialized services, arbitration arrangements, the purchaser efficiency index
      and contracts with the independent sector. The final section offers some
      concluding thoughts on the current state and future of contracting in the NHS.

PMID- 8880173
TI  - Technical, scale, and size efficiency in nursing home care: a nonparametric
      analysis of Connecticut homes.
AB  - Maindiratta (1990) questioned the usefulness of the concept of scale efficiency
      in production as the most productive scale size (MPSS) usually requires altering
      the scale of output produced. If the decision making unit (DMU) is required to
      deliver a specific output bundle, then altering output along with the input scale
      to reach the MPSS is not a valid recommendation. He proposed a measure of the
      size efficiency of a DMU. In this paper, we apply Data Envelopment Analysis (DEA)
      to examine the levels of technical, scale, and size efficiency of individual
      nursing homes providing health care to the elderly. The data used relate to the
      operations of 140 nursing homes from Connecticut, USA during the year 1982-83.
      Maindiratta's model is input-oriented. By contrast, our study is output-oriented
      and we appropriately reformulate Maindiratta's model. The findings show that in
      several cases size efficiency is less than unity. This suggests that the most
      efficient production of output would require restructuring of the nursing home
      under investigation as more than one small unit. We also compare the efficiency
      levels of 'for-profit' homes with those of 'not-for-profit' homes.

PMID- 8880174
TI  - Finding health resources on the Internet--the departure lounge.
AB  - As with all other areas of research, the influence of the Internet on health
      economics will continue to grow. The availability of information is central to
      the UK health reforms and plans are afoot to create an NHS network. Harnessing
      the power of the Net has become a basic research skill. This involves information
      and data capture, work sharing and communication as well as dissemination of our
      own work findings. You might optimistically regard the Internet as a system of
      arteries and arterioles through which oxygen of information may flow effectively
      to those who need it. However, users are sometimes frustrated by slow access,
      poorly indexed information and lots of noise: successful use sometimes seems
      reliant on serendipity. The Departure Lounge will try to keep you up to speed
      with developments.

PMID- 8880175
TI  - The hair cell acetylcholine receptors: a synthesis.
AB  - In this article the evidence concerning the nature of the acetylcholine (ACh)
      receptors on hair cells is reviewed. A schematic organization of these receptors
      is offered, based on the evidence as follows. (1) There are two kinds of ACh
      receptors on hair cells: muscarinic-like and nicotinic-like. (2) The nicotinic
      like receptor mediates a hyperpolarizing response to ACh and a consequent
      reduction in afferent firing. (3) The muscarinic-like receptors mediate both a
      depolarization and a hyperpolarization of hair cells. (4) The hyperpolarization
      results in a reduction in afferent firing and (5) the depolarization results in
      an increase in afferent firing.

PMID- 8880176
TI  - Differences in cholinergic responses from outer hair cells of rat and guinea pig.
AB  - A cholinergic receptor on outer hair cells (OHC) in guinea pig cochlea induces a
      K+ current when it is activated by acetylcholine and suberyldicholine but not by
      nicotine or muscarine (Bobbin, 1995). This unusual receptor may contain an alpha
      9-subunit. However, the pharmacology of the alpha 9-subunit cloned from rat and
      expressed in Xenopus oocytes does not completely match that obtained for the ACh
      receptor in guinea pig OHCs. The response to 1,1-dimethyl-4-phenylpiperazinium
      (DMPP) is large in guinea pig OHCs and small in oocytes containing receptors of
      the alpha 9-subunit. Therefore, we compared the effects of cholinergic receptor
      agonists in rat and guinea pig OHCs using the whole-cell variant of the patch
      clamp technique. ACh caused the largest outward K+ current in OHCs from both rat
      and guinea pig. Carbachol- and suberyldicholine-induced responses were similar in
      magnitude in OHCs of rat and guinea pig. However, DMPP produced a small response
      in OHCs from rat and a large response in OHCs from guinea pig. At a concentration
      of 100 microM, muscarine, oxotremorine M, nicotine and cytisine induced little
      response in guinea pig OHCs and none in rat OHCs. Results suggest that the ACh
      receptor on rat OHCs is similar to the alpha 9-subunit-containing receptor
      expressed in oocytes but different from the ACh receptor on guinea pig OHCs.

PMID- 8880177
TI  - Phenotypic patterns of distortion product otoacoustic emission in inbred and F1
      hybrid hearing mouse strains.
AB  - Distortion product otoacoustic emissions (DPOE) were obtained from five different
      hearing mouse groups: CBA/J, MOLF/Rk, ct (homozygous normal mice of the curly
      tail stock), and the F1 hybrid offspring of the matings CBA/J x dn/dn and MOLF/Rk
      x dn/dn (dn/dn mice are the curly-tail stock with recessive deafness). The DPOE
      patterns of the CBA/J and ct strains were similar to each other and different
      from that of the MOLF/Rk. The two sets of F1 hybrid mice, (CBA/J x dn/dn)F1 and
      (MOLF/Rk x dn/dn)F1, were found to have significantly larger DPOE amplitudes than
      their hearing parent strains, MOLF/Rk and CBA/J, respectively. In addition, the
      DPOE amplitudes were greater for the offspring of the MOLF/Rk x dn/dn cross than
      for those of the CBA/J x dn/dn cross, even though they were lower for MOLF/Rk
      than for CBA/J. The distinct features of DPOE patterns among these five groups
      suggest that DPOE testing can be used for auditory phenotyping.

PMID- 8880178
TI  - Temperature dependence of spontaneous otoacoustic emissions in the edible frog
      (Rana esculenta).
AB  - The change in frequency of individual emissions in the European edible frog (Rana
      esculenta) when the temperature of the frog is modified, is part of a complex
      pattern of interaction between spontaneous otoacoustic emissions. At high
      temperatures (above 24 degrees C) two emissions are always detected (e.g., one
      near 800 Hz and one near 1200 Hz). The higher-frequency emission is lower in
      level and has a wider bandwidth than the lower-frequency emission. It is also
      often asymmetric and sometimes breaks into two emissions when an external
      suppressor tone is applied. When the temperature is decreased, these emissions
      are reduced in frequency at a rate of 0.04 octave/degree C. The higher-frequency
      emission becomes narrower and taller, and the lower-frequency emissions becomes
      broader and less intense. At approximately 18 degrees C the lowest of these
      emissions (now between 600 and 700 Hz) disappears and is replaced by a new
      emission approximately 100 Hz lower in frequency. When the temperature is
      carefully controlled the two emissions can exist simultaneously. The lowest
      frequency emission changes 0.015 degree C/octave suggesting that the mechanisms
      controlling the frequency of this emission may be different than those
      determining the frequencies of the other emissions. All but the lowest-frequency
      emissions are maximal in level and have minimal bandwidth when the frequency is
      close to 700 Hz, which is interpreted as evidence that these emissions are
      filtered by a temperature-independent process.

PMID- 8880180
TI  - Distortion product otoacoustic emission suppression tuning curves in human adults
      and neonates.
AB  - Distortion product otoacoustic emission (DPOAE) iso-suppression tuning curves
      (STC) were generated in 15 normal-hearing adults and 16 healthy term-born
      neonates for three f2 frequencies. The 2f1-f2 DPOAE was elicited using f2/f1 =
      1.2, LI = 1.2, LI = 65 and L2 = 50 dB SPL. A suppressor tone was presented at
      frequencies ranging from 1 octave below to 1/4 octave above f2 and varied in
      level until DPOAE amplitude was reduced by 6 dB. The suppressor level required
      for 6 dB suppression was plotted as function of suppressor frequency to generate
      a DPOAE STC. Forward-masked psychoacoustic tuning curves (PTC) were obtained for
      three of the adult subjects. Results indicate that DPOAE STCs are stable and show
      minimal inter- and intra-subject variability. The tip of the STC is consistently
      centered around the f2 region and STCs are similar in shape, width (Q10) and
      slope to VIIIth-nerve TCs. PTCs and STCs measured in the same subject showed
      similar trends, although PTCs had narrower width and steeper slope. Neonatal STCs
      were recorded at 3000 and 6000 Hz only and were comparable in shape, width and
      slope to adult STCs. Results suggest: (1) suppression of the 2f1-f2 DPOAE may
      provide an indirect measure of cochlear frequency resolution in humans and (2)
      cochlear tuning, and associated active processes in the cochlea, are mature by
      term birth for at least mid- and high-frequencies. These results provide
      significant impetus for continued study of DPOAE suppression as a means of
      evaluating cochlear frequency resolution in humans.

PMID- 8880179
TI  - Regional distribution of a creatine transporter in rat auditory brainstem: an in
      situ hybridization study.
AB  - The expression of an mRNA encoding a creatine transporter (CRT1) was investigated
      in the rat auditory system under ambient sound conditions, using radiolabeled and
      non-radiolabeled oligonucleotide in-situ hybridization. The results indicated
      that CRT1 mRNA is widely distributed in auditory nuclei, including the fusiform
      and deep layers of the dorsal cochlear nucleus, the ventral cochlear nucleus, the
      superior olivary complex, the nuclei of the lateral lemniscus and the inferior
      colliculus. The molecular layer of the dorsal cochlear nucleus and the medial
      geniculate have low levels of label. Creatine provides cells with a reservoir of
      high-energy phosphate. Neurons do not synthesize creatine but accumulate it by a
      transport mechanism, which is probably the limiting step in the regulation of
      intracellular creatine. Therefore, the quantity of transporter expressed may
      reflect the utilization of creatine and could serve as an in-vitro indicator of
      endogenous high-energy metabolism in some cells. Although most auditory nuclei
      express CRT1 mRNA, the quantity of CRT1 mRNA varies among auditory nuclei,
      indicating that many auditory nuclei have high and fluctuating energy
      requirements. The level of CRT1 transcript or protein may be regulated by chronic
      metabolic changes in the auditory system that may occur, for example, with damage
      to the acoustic organ or the aging process.

PMID- 8880181
TI  - Evoked otoacoustic emissions and auditory selective attention.
AB  - The auditory system has an extensive peripheral efferent innervation. The
      question addressed in this paper is whether the olivocochlear bundle (OCB)
      efferent system innervating the outer hair cells (OHC) of the cochlea plays a
      role in selective attention. As evoked otoacoustic emissions (EOAE) provide a
      measure of the active micromechanical properties of OHCs, they can be used to
      assess the role of the efferent system in attention. Six experiments using tone
      pip EOAEs are reported. In each experiment, EOAEs generated by 1 or 2 kHz tone
      pips when they were attended were compared with EOAEs to the same stimuli when
      they were unattended. In three experiments (1-4), a non-linear stimulus
      difference method was used to record a pure cochlear component of EOAEs. In Exps.
      1-5, 1 and 2 kHz tone pips were delivered to the same ear and the difficulty of
      the subjects' task was manipulated in order to produce a more focussed
      attentional state or contralateral noise was presented to determine whether
      attention effects are dependent upon having an already activated efferent system.
      In Exp.6, the 1 and 2 kHz stimuli were delivered to opposite ears. A total of 70
      subjects participated in the six experiments. There were no effects of attention
      on EOAEs in any of the experiments in the direction of previously reported
      effects. The results of these first six experiments employing simple attention
      switches between fixed auditory objects do not support active cochlear
      involvement in selective attention.

PMID- 8880182
TI  - Chronic low-level noise exposure alters distortion product otoacoustic emissions.
AB  - Chen et al. (1995) recently reported an altered response to the application of
      ATP in outer hair cells (OHC) isolated from guinea pigs continuously exposed for
      10 or 11 days to a 65 dB SPL (A-scale) narrow-band noise (1.1-2.0 kHz). The
      primary goal of the present study was to test the hypothesis that the continuous
      low-level noise used by Chen et al. (1995) alters cochlear function. Cubic (2f1
      f2) and quadratic (f2-f1) DPOAEs, as well as, the amount of contralateral
      suppression of DPOAE amplitudes were chosen for study. Responses were recorded in
      urethane-anesthetized guinea pigs with sectioned middle ear muscles. The animals
      had either been exposed to the low-level noise for 3 or 11 days or not exposed at
      all (n = 13 animals per group). Results demonstrate that this noise induces
      frequency-dependent and very localized reductions in 2f1-f2 DPOAE input/output
      (I/O) functions. However, the f2-f1 DPOAE I/O functions appear to be insensitive
      to the noise exposure. No noise-related changes were found in the amount of
      contralateral suppression between the different exposure groups, with the
      exception of one unexplainable data point (f2-f1 DPOAE = 0.5 kHz; day 3) where it
      was reduced. The 2f1-f2 DPOAE amplitude alterations lend support to the
      conclusions of Chen et al. (1995) that chronic low-level noise exposure induces
      molecular changes in the OHCs which may, in turn, alter cochlear function.

PMID- 8880183
TI  - Effects of pulse separation on detection thresholds for electrical stimulation of
      the human cochlea.
AB  - Effects of pulse separation on detection of electrical stimulation of the cochlea
      were studied in 12 profoundly deaf human subjects with Nucleus 22 cochlear
      implants. Biphasic symmetric pulses were used. Pulse separation is the time from
      offset of one biphasic pulse to the onset of the next biphasic pulse in the
      train. Effects of pulse separation were studied in the context of different
      covariables in four stages of the experiment. Effects of pulse separation seen in
      the different stages were similar, despite the different covariables. Both pulse
      separation and the total number of pulses per stimulus seem to be important
      variables affecting stimulus detection. For 0.5 ms/phase pulses, thresholds were
      lowest at the shortest pulse separations tested (0.2-1.1 ms) and increased as a
      function of pulse separation. For 2 ms/phase pulses, detection thresholds were
      lowest at pulse separations around 7.5 ms, in most cases, and higher at both
      longer and shorter pulse separations. These results suggest that interactions
      among adjacent pulses can either hinder or facilitate detection of the signal
      depending on the magnitudes of pulse separation and phase duration. Pulse
      separations at which thresholds measured for 2 ms/phase pulses were minimum were
      fairly consistent across subjects and did not correlate well with speech
      recognition scores. However, significant variation in this measure across species
      has been seen.

PMID- 8880184
TI  - Sensitive developmental periods for kanamycin ototoxic effects on distortion
      product otoacoustic emissions.
AB  - The developing rat is hypersensitive to aminoglycoside toxicity, which is
      expressed early on as a destruction of outer hair cells (OHC). In the current
      study, distortion-product otoacoustic emissions (DPOAE), which specifically
      measure the micromechanical activity of OHCs, were used to assess functional
      effects of administering a regimen of kanamycin to three groups of neonatal rats
      representing discrete postnatal developmental periods. In this manner, pigmented
      rats were treated at postnatal days 1-10, 11-20, and 21-30. A series of input
      output (I/O) functions obtained for the 2f1-f2 DPOAE during the post-treatment
      period indicated that detection thresholds were significantly elevated for the
      animals treated on postnatal days 1-10 and 11-20, with the greatest elevations
      observed at the higher test frequencies.

PMID- 8880185
TI  - The acoustic two-tone distortions 2f1-f2 and f2-f1 and their possible relation to
      changes in the operating point of the cochlear amplifier.
AB  - Acoustic two-tone distortions are generated during non-linear mechanical
      amplification in the cochlea. Generation of the cubic distortion 2f1-f2 depends
      on asymmetric components of a non-linear transfer function whereas the difference
      tone f2-f1 relies on symmetric components. Therefore, a change of the operating
      point and hence the symmetry of the cochlear amplifier could be strongly
      reflected in the level of the f2-f1 distortion. To test this hypothesis, low
      frequency tones (5 Hz) were used to bias the position of the cochlear partition
      in the gerbil. Phase-correlated changes of f2-f1 occurred at bias tone levels
      where there were almost no effects on 2f1-f2. Higher levels of the bias tone
      induced pronounced changes of both distortions. These results are qualitatively
      in good agreement with the results of a simulation in which the operating point
      of a Boltzman function was shifted. This function is similar to those used to
      describe outer hair cell (OHC) transduction. To influence OHC motility,
      salicylate was injected. It caused a decrease of the 2f1-f2 level and an increase
      in the level of f2-f1. Such reciprocal changes of both distortions, again, can be
      interpreted in terms of a shift of the operating point of the cochlear amplifier
      along a non-linear transfer characteristic. To directly influence the cochlear
      amplifier, DC current was injected into the scala media. Large negative currents
      (> -2 microA) caused a pronounced decrease of 2f1-f2 (> 15 dB) and positive
      currents had more complex effects with increasing and/or decreasing 2f1-f2
      distortion level. The effects were time and primary level dependent. Changes of
      f2-f1 for DC currents > magnitude of mu 2A were in most cases larger compared to
      2f1-f2 and reversed for certain primary levels. The current effects probably
      result from a combination of changing the endocochlear potential and shifting the
      operating point along a non-linear transfer function.

PMID- 8880186
TI  - Direct detection of ototoxicant-induced reactive oxygen species generation in
      cochlear explants.
AB  - The proposal that free-radical generation contributes to the ototoxicities of
      several chemical agents was studied utilizing electron paramagnetic resonance
      (EPR) spectrometry to detect directly ototoxicant-induced reactive oxygen species
      formation in cochlear tissue. Guinea pig cochlear explants in chelexed artificial
      perilymph (AP: 200 microliters) were exposed to an ototoxicant or AP for 10 min.
      Ototoxic agents included gentamicin sulfate (4.0 mM), kanamycin monosulfate (4.0
      mM), ethacrynic acid (0.5 mM), furosemide (0.3 mM), cisplatin (0.1 mM),
      trimethyltin chloride (0.1 mM), and quinine HCl (3.0 mM). Following incubation,
      20 microliters of AP/ototoxicant mixture was replaced by the filtered spin trap,
      5,5-dimethylpyrroline-N-oxide (DMPO). After 10 min, the EPR spectrum of the
      mixture was obtained. Four line EPR spectra of relative intensities 1:2:2:1,
      associated with hydroxyl radical (OH)/DMPO adduct formation, were evidenced by
      reaction mixtures containing cochlear explants exposed to each ototoxicant.
      Cisplatin, quinine and the loop diuretics produced weak OH-associated EPR signals
      in the absence of a cochlear explant, which were amplified in its presence.
      Deferoxamine quenched all OH spectral peaks. Peroxide levels, assayed in parallel
      experiments, were diminished by each ototoxicant relative to those seen following
      AP exposure, suggesting possible H2O2 conversion to OH. These data support the
      proposal that various ototoxic agents are capable of reactive oxygen species
      generation or promotion in cochlear tissues.

PMID- 8880187
TI  - Frequency-specific identification of hearing loss using transient-evoked
      otoacoustic emissions to clicks and tones.
AB  - Transient-evoked otoacoustic emissions (TEOAE) to clicks and to 500- and 2000-Hz
      brief tones were measured in 72 normal-hearing and hearing-impaired subjects (86
      ears). The TEOAE's reproducibility parameter was used for the analyses. The
      purpose of the investigation was to determine which stimuli best predicted the
      presence of sensorineural hearing loss in a frequency-specific manner at 500,
      1000, 2000, and 4000 Hz. Analyses of the TEOAEs filtered into frequency-specific
      bands showed that separation of normal and impaired ears at 1000, 2000 and 4000
      Hz was best achieved by TEOAEs evoked by clicks. Identification of hearing loss
      at 500 Hz was best obtained using 500-Hz tone-evoked TEOAEs filtered using a band
      centered at 500 Hz. Octave- and half-octave-wide bands identified hearing loss
      equally well. An analysis sweep time of 20 ms provided slightly better results
      compared to 30 ms, except for 500 Hz, where the 30-ms sweep time slightly
      improved the identification of hearing loss. Increases in the audiometric
      criterion did not yield better test performance once hearing loss exceeded 20 dB
      HL. The findings from this study suggest that the combination of bandpass
      filtered TEOAEs to clicks and TEOAEs to 500-Hz tones identifies with reasonable
      accuracy ears with sensorineural hearing loss at 500, 1000, 2000, and 4000 Hz.

PMID- 8880188
TI  - Responses to exponential frequency modulations in the rat inferior colliculus.
AB  - We examined responses to pure tones and exponentially frequency-modulated (FM)
      stimuli in the inferior colliculus of ketamine anesthetized rats. All units
      responded to both pure-tone and FM stimulation: units responding selectively to
      FM stimuli were not found. The comparison between responses to many different FM
      sweeps revealed that activity was elicited when the instantaneous frequency of a
      FM sweep entered the unit's pure-tone tuning curve. Units were tuned to the rate
      of frequency modulation. Most modulation rate transfer functions had bandpass
      characteristics. Best modulation rates covered a range from 4.8 to 1904 octaves/s
      with more than 90% between 10 and 400 octaves/s. In contrast to previous studies,
      modulation direction was not coded in unit responses and only few units
      demonstrated a weak change in response strength when sweep direction was altered.
      This is at least partly attributable to the FM stimulus design which, in the
      present study, was adapted to the logarithmic frequency representation in the rat
      auditory system and carefully matched to the units' pure-tone responses area. In
      spite of the close relationship between pure tone and FM response behavior,
      modulation rate tuning cannot be completely explained on the basis of the units'
      pure-tone responses.

PMID- 8880189
TI  - Tuning, spontaneous activity and tonotopic map in chicken cochlear ganglion
      neurons following sound-induced hair cell loss and regeneration.
AB  - Adult chickens were exposed for 48 h to a 525 Hz, 120 dB SPL tone that destroyed
      the hair cells and tectorial membrane in a crescent-shaped patch along the
      abneural edge of the basilar papilla. Single-unit recordings were obtained from
      cochlear ganglion neurons 0-1, 5, 14 and 28 days post-exposure to determine what
      effect the cochlear lesion had on neural discharge patterns and if the discharge
      patterns fully recovered. Immediately after exposure, the tuning curves were
      extremely broad and CF thresholds were elevated by 30-40 dB. In addition, the
      average spontaneous rate and percentage of neurons with interspike interval
      histograms with preferred intervals were greatly reduced. Tuning curves and
      spontaneous activity started to recover by 5 days post-exposure; however, some W
      shaped tuning curves with two distinct tips and a hypersensitive tail were
      observed at this time. W-shaped tuning curves disappeared and spontaneous
      activity recovered to normal levels 14-28 days post-exposure. However, the CF
      thresholds of the most sensitive neurons were still slightly elevated, tuning
      curve slopes below CF were shallower than normal, and thresholds in the low
      frequency tail of the tuning curves were often hypersensitive. These functional
      deficits were most closely associated with residual damage to the upper fibrous
      layer of the tectorial membrane. To determine if the cochlear frequency-place map
      was altered by the cochlear lesion, four physiologically characterized neurons
      were labeled with biocytin at 5 days post-exposure. The CFs of the labeled
      neurons were consistent with the normal frequency-place map (Chen et al. (1994)
      Hearing Research 81, 130-136) indicating that the tonotopic map was not altered.

PMID- 8880190
TI  - Frequency response for electromotility of isolated outer hair cells of the guinea
      pig.
AB  - Frequency and impulse responses were determined for isolated guinea pig outer
      hair cells by electrically stimulating the cells between two wire electrodes with
      white noise. Cells were attached to the bottom of a small culture dish at one end
      while the other end was freely moving. Results have the character of a damped
      second-order system, with a cut-off frequency of approximately 7 kHz.
      Correspondingly, impulse responses show a single narrow peak roughly 50
      microseconds wide and have the shape of the impulse response for a critically
      damped harmonic oscillator.

PMID- 8880191
TI  - Effects of parallel fiber stimulation on neurons of rat dorsal cochlear nucleus.
AB  - We have compared the effects of parallel fiber stimuli on extracellularly
      recorded neurons showing regular or bursting spontaneous activity patterns in the
      dorsal cochlear nucleus of rat brainstem slices. Ninety percent of regular
      neurons failed to respond to stimulus currents (1.4 +/- 0.28 mA, mean +/- SEM)
      significantly greater than those (0.4 +/- 0.07 mA) that elicited responses from
      96% of bursting neurons. Responses of bursting neurons were elicited from widely
      separated loci along the molecular layer. Kynurenic acid and CNQX or DNQX blocked
      both spontaneous firing and responses to parallel fiber stimuli of bursting
      neurons. The same agents also blocked responses of regular neurons but had little
      or no effect on their spontaneous firing rates. AP-5 caused small decreases in
      spontaneous rates of both bursting and regular neurons but did not appear to
      affect responses to stimuli. The data support the hypothesis that the responses
      of both regular and bursting neurons to parallel fiber stimulation are mediated
      by glutamate, acting mainly through non-NMDA receptors. Spontaneous activity of
      bursting, but not regular, neurons also requires non-NMDA glutamatergic
      transmission, suggesting that the spontaneous firing of bursting neurons,
      consisting largely of cartwheel cells, may depend upon granule cell activity.

PMID- 8880192
TI  - The epidemiology of AIDS--related neoplasms.
AB  - The magnitude for and risk factors of the two most important AIDS neoplasm,
      Kaposi's sarcoma and non-Hodgkin's lymphoma, are reviewed in detail. The
      association between AIDS and other cancers is mostly speculative because
      surveillance biases tend to favor detecting associations that may be spurious.
      The overall relative risk of other cancers appears, however, to be only twofold
      above that in the general population, with associations being most convincing for
      anal (but not cervical) cancer and leiomyosarcoma and possible also for Hodgkin's
      disease, testicular cancer, and conjunctival cancers.

PMID- 8880193
TI  - Pathogenesis of AIDS--related Kaposi's sarcoma. Evidence of a viral etiology.
AB  - Kaposi's sarcoma is the most common malignancy in patients with HIV infection.
      New studies point to the involvement of a new human Kaposi's sarcoma herpes virus
      (KSHV) as a transforming agent. After transformation, cytokine perturbations
      facilitate growth and in some cases clonal growth occurs. This results in a
      malignancy with devastating clinical consequences. A clear understanding of the
      mechanism of transformation by KSHV will lead to better therapies.

PMID- 8880194
TI  - Clinical presentation and natural history of AIDS--related Kaposi's sarcoma.
AB  - The clinical course of KS is highly variable, ranging from minimal disease to
      explosive growth. Extracutaneous spread is common, involving most frequently the
      oral cavity, GI tract, lungs, and lymph nodes. Both corticosteroid therapy and
      opportunistic infections are associated with the development of KS and with
      exacerbation of pre-existing KS in HIV-infected patients. A typical initial
      evaluation includes a thorough physical examination, fecal occult blood test,
      chest roentgenogram, and CD4+ T-lymphocyte count. The staging system most
      commonly used groups patients according to extent of tumor, immune status, and
      severity of systemic illness. After adjusting for prognostic factors, the most
      important of which is the median CD4+ T-lymphocyte count at presentation the
      survival of patients with KS is improving as the AIDS epidemic matures.

PMID- 8880195
TI  - AIDS-related Kaposi's sarcoma. A template for the translation of molecular
      pathogenesis into targeted therapeutic approaches.
AB  - AIDS-related Kaposi's sarcoma (KS) represents a complex interaction of host and
      viral factors. There are a number of fundamental questions surrounding the
      interplay between the disparate factors that can contribute to the pathogenesis
      and pathophysiology of this disease. Targets such as the enhancement of immune
      function, inhibition of angiogenic factors or immunostimulatory cytokines,
      inhibition of viral proteins such as Tat, or hormonal manipulations are now or
      will in the future become the focus of research to develop innovative anti-KS
      therapy and prevention measures. Antiviral approaches aimed at HIV or other
      viruses may potentially target a number of steps in KS pathogenesis. This article
      reviews diverse modalities--cytotoxic, antiviral, gene-directed, growth factor
      targeted, and antiangiogenesis--that singly, or more likely in combination, stand
      to make an impact on the cure and prevention of AIDS-related KS.

PMID- 8880196
TI  - Chemotherapy of AIDS--related Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is the most common tumor associated with AIDS. A growing
      number of patients with this tumor are presenting at later stages of HIV with
      more rapidly progressive, extensive, or symptomatic KS or with tumors involving
      visceral organs. Chemotherapy treatment is effective in inducing tumor
      regression, reducing edema, and ameliorating symptoms caused by these tumors.
      Side effects and toxicities from these agents, however, can be quite pronounced,
      especially in patients with advanced AIDS Antiretroviral therapy, prophylaxis for
      opportunistic infections, and the use of hematopoietic growth factors should be
      routinely included in the management of these patients. Newer chemotherapeutic
      agents and combination regimens may be more effective or less toxic than
      previously evaluated regimens.

PMID- 8880197
TI  - The role of radiation therapy in the management of HIV-related Kaposi's sarcoma.
AB  - Radiation provides excellent palliation for symptomatic Kaposi's sarcoma in the
      settings of both limited and advanced disease. Integration of radiotherapy into
      the overall treatment strategy is critical to ensure that the benefits in terms
      of symptom reduction are not outweighed by a long-term increase in morbidity.

PMID- 8880198
TI  - Etiology and pathogenesis of AIDS-related non--Hodgkin's lymphoma.
AB  - The incidence of NHL is greatly increased in HIV-infected individuals. The vast
      majority are clinically aggressive B cell-derived neoplasms exhibiting BL, IBL,
      or LCL histology. Approximately 80% arise systemically (nodal and/or extranodal),
      and the remaining 20% arise as primary CNS lymphomas. A small proportion are body
      cavity-based lymphomas associated with KSHV infection. Possible factors
      contributing to lymphoma development include HIV-induced immunosuppression,
      chronic antigenic stimulation, and cytokine overproduction. These alterations are
      associated with the development of oligoclonal B-cell expansions. The appearance
      of NHL is characterized by the presence of a monoclonal B-cell population
      displaying a variety of genetic lesions, including EBV infection, c-myc gene
      rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53
      mutations/deletions. The number and type of genetic lesions varies according to
      the anatomic site and histopathology. In the case of BL, virtually 100% exhibit c
      myc gene rearrangements, two thirds display p53 gene mutations, one third contain
      EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of IBL,
      virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display
      bcl-6 gene rearrangements, and very few exhibit p53 gene mutations. These
      findings suggest that more than one pathogenetic mechanism is operational in the
      development and progression of AIDS-related NHLs. Further work will be necessary
      to develop a complete understanding of the etiology and pathogenesis of NHL in
      the setting of HIV infection. AIDS-related NHL remains an important biologic
      model for investigating the development and progression of high-grade NHLs as
      well as NHLs that develop in immune-deficient hosts.

PMID- 8880199
TI  - Diagnosis and management of systemic non-Hodgkin's lymphoma in HIV disease.
AB  - Persons with HIV infection are at an increased risk of developing intermediate
      and high-grade non-Hodgkin's lymphomas. Patients present with wide-spread
      extranodal disease at the time of initial presentation, with unusual sites of
      disease common. Factors predictive of a poor prognosis are low performance
      status, history of AIDS prior to the diagnosis of lymphoma, bone marrow
      involvement, and low CD4 count. Experience suggests that in some patients, more
      aggressive chemotherapy may be associated with shortened survival time. Recent
      clinical trials have demonstrated that the use of either myeloid growth factors
      or reduced-dosage chemotherapeutic regimens can reduce the morbidity associated
      with chemotherapy. A number of new and exciting experimental treatments are now
      in clinical development. These include new chemotherapy-based regimens, immune
      modulators immunotoxin therapy, and cellular therapy. It is hoped that as we
      continue to learn more about the biology of the HIV-associated lymphomas, we can
      develop more rational and effective treatment modlities that take advantage of
      the unique molecular characteristics of these tumors.

PMID- 8880200
TI  - Biology and management of AIDS-associated primary CNS lymphomas.
AB  - Primary central nervous system (CNS) lymphoma is the most common brain tumor in
      patients with AIDS and occurs in about 10% of this population. CT/MR scan usually
      demonstrates single or multiple contrast enhancing masses that are
      radiographically indistinguishable from other CNS processes such as
      toxoplasmosis. Brain biopsy, positive cerebrospinal fluid (CSF) cytology, or
      possibly the demonstration of Epstein-Barr viral DNA in the CSF can establish the
      diagnosis. Cranial radiotherapy (RT) has been the cornerstone of therapy and
      produces responses in most patients, but their median survival is still only a
      few months. The addition of chemotherapy to RT may prolong survival in a sub
      group of patients.

PMID- 8880201
TI  - HIV-associated Hodgkin's disease. Biologic and clinical aspects.
AB  - The incidence of HD appears to have increased in HIV-infected individuals, with
      HIV-seropositive intravenous drug users most likely to develop the disorder. All
      groups at risk for HIV, however, may develop HD. The pathologic spectrum of HD in
      the setting of HIV infection is distinct from that seen in "de novo" HD in the
      United States, with the majority of patients diagnosed with the mixed cellularity
      subtype, as opposed to the more usual occurrence of nodular sclerosis in "de
      novo" disease. The presence of fibrohistiocytic stromal cells within involved
      tissues is also a distinct characteristic of HIV-associated HD. Epstein-Barr
      viral genome has been detected within tumor cell nuclei, and it may be involved
      in the pathogenesis of disease. Clinically, patients often present with systemic
      "B" symptoms and widely disseminated extranodal disease, seen in 75% to 90%. Bone
      marrow is involved in 40% to 50% of cases at diagnosis. Complete remission may be
      achieved in approximately 50% of patients after use of combination chemotherapy,
      but median survival is short, in the range of 12 to 18 months. Death is often due
      to bacterial or opportunistic infection (or both), often occurring in the setting
      of chemotherapy-induced neutropenia.

PMID- 8880202
TI  - Hematologic disorders and growth factor support in HIV infection.
AB  - During the course of HIV disease a broad spectrum of hematologic disorders
      develop including abnormalities in blood cell generation, survival, and function
      Alterations in coagulation parameters may evolve associated with disruption of
      immunoglobulin or factor production. This article reviews the manifestations and
      pathophysiology of these abnormalities and discusses the role for growth factor
      support.

PMID- 8880203
TI  - Cervical neoplasia. Pathogenesis, diagnosis, and management.
AB  - Cervical neoplasia is a common problem among HIV-infected women. HIV appears to
      accelerate human papillomavirus-related oncogenic events via in completely
      understood mechanisms. Cytologic screening for cervical neoplasia appears to be
      unreliable in HIV-infected women. Treatment is also not very effective. Invasive
      cervical cancer in particular has a very poor prognosis. Innovative therapeutic
      modalities are currently being investigated.

PMID- 8880204
TI  - Anal neoplasia. Pathogenesis, diagnosis, and management.
AB  - Prolonged, severe immunodeficiency provides the necessary milieu for the
      emergence of anogenital neoplasia caused by human papillomaviruses. Anal
      neoplasia is likely to become a more common manifestation of HIV disease as
      patients with profound immunodeficiency, who would have succumbed to
      opportunistic infections earlier in the epidemic, are now surviving for extended
      periods of time because of increasingly effective antiretroviral, prophylactic,
      and antimicrobial therapies. The screening and treatment strategies described for
      use in HIV-infected patients with anal neoplasia are currently being investigated
      and refined.

PMID- 8880205
TI  - Cancers in children with HIV infection.
AB  - Malignancies in children with HIV infection have not been as frequent as
      expected, but they still constitute a fertile area for clinical and basic
      research. Non-Hodgkin's lymphomas are the most frequent malignancies of children
      with AIDS and are curable diseases with standard chemotherapy. Leiomyomas and
      leiomyosarcomas have become the second leading cancer of children with HIV
      infection and are clearly associated with EBV infection. Treatment for these
      lesions has not been as successful as that for lymphomas. Other infrequent
      atypical lymphoproliferative lesions of these patients can often be categorized
      in the MALT group. Some of these are low-grade lymphomas, whereas others can
      progress to high grade. The diagnosis of Kaposi's sarcoma in children with AIDS
      should be carefully reviewed by pathologists experienced with these cases. The
      diagnosis of KS in children must be made with special care, because some other
      lesions of HIV-infected children (such as prominent vascularity in lymph nodes)
      can be confused with KS. Other tumors of these patients are rare and probably are
      no more frequent than would be expected in the normal population. Because
      malignancies in children with AIDS are rare, it is important that each one be
      studied completely with regard to type and incidence, risk factors, and biologic
      features. To this end, the Pediatric Oncology Group (POG) has established a
      national registry and treatment protocols. Patient information as well as fresh,
      frozen, and fixed specimen studies are coordinated through the POG Statistical
      Office in Gainesville, Florida (telephone, 904-392-5198; FAX, 904-392-8162). The
      collaborative efforts of all physicians treating children with AIDS and
      malignancies will be needed to advance our knowledge and efficacy in treating
      these diseases.

PMID- 8880206
TI  - Non-AIDS-defining cancers.
AB  - As the AIDS epidemic advances, the spectrum of malignancies encountered is
      expanding. Several non-AIDS-defining cancers are seen in increased incidence in
      HIV-infected patients. These include basal cell carcinoma of the skin, squamous
      cell carcinoma of the anus, Hodgkin's disease, seminoma, and pediatric
      leiomyosarcoma. There appears to be an emerging role for various concurrent viral
      infections in the HIV-infected host that are likely implicated in the
      pathogenesis of AIDS-related neoplasms. It will be important to track the
      epidemiologic and biologic features of non-AIDS cancers in HIV-infected patients.
      It is likely that further clues about malignant transformation and oncogenesis
      unraveled in this setting will have broader clinical implications.

PMID- 8880207
TI  - Evaluation of the potential carcinogenicity and genetic toxicity to humans of the
      herbicide acetochlor.
AB  - Comprehensive toxicological studies of the herbicide acetochlor are presented and
      discussed. Although it gave a negative profile of responses in the many toxicity
      tests conducted there were some findings that prompted further investigation.
      First, although non-mutagenic in the Salmonella assay, acetochlor was clastogenic
      to mammalian cells treated in vitro. This clastogenic potential was not expressed
      in vivo in four rodent cytogenetic assays (bone marrow and germ cells). Second,
      although acetochlor gave a negative response in rat liver UDS assays when tested
      at the acute MTD, gavage administration of a single, supra-MTD dose (2000 mg/kg)
      gave a weak positive assay response. This dose-level (2000 mg/kg) was necrotic to
      the liver, depressed hepatic glutathione levels by up to approximately 80%,
      altered the metabolism of acetochlor, and was associated with up to 33%
      lethality. In contrast, reference liver genotoxins such as DMN, DMH and 2AAF were
      shown to elicit UDS in the absence of such effects, and at approximately 400 x
      lower dose-levels. Finally, microscopic nasal polypoid adenomas were induced in
      the rat when acetochlor was administered for two years at the maximum tolerated
      dose (MTD). The tumours were not life-threatening, they did not metastasize, and
      no DNA damage was induced in the nasal cells of rats maintained on a diet
      containing the MTD of acetochlor for either 1 or 18 weeks (comet assay). In order
      to probe the mechanism of action of these high dose toxicities a series of
      chemical and genetic toxicity studies was conducted on acetochlor and a range of
      structural analogues. These revealed the chloroacetyl substructure to be the
      clastogenic species in vitro. Although relatively inert, this substituent is
      preferentially reactive to sulphydryl groupings, most evidently, to glutathione
      (GSH). Similar chemical reactivity and clastogenicity in vitro was observed for
      two related chemicals bearing a chloroacetyl group, both of which have been
      defined as non-carcinogens in studies reported by the US.NTP. These collective
      observations indicate that the source of the clastogenicity of acetochlor in
      vitro is also the source of its rapid detoxification in the rat in vivo, via
      reaction with GSH. Metabolic studies of acetochlor are described which reveal the
      formation of a series of GSH-associated biliary metabolites in the rat that were
      not produced in the mouse. The metabolism of acetochlor in the rat changes with
      increasing dose-levels, probably because of depletion of hepatic GSH. It is most
      likely that a rat-specific metabolite is responsible for the rat nasal tumours
      observed uniquely at elevated dose-levels. The absence of genetic toxicity to the
      nasal epithelium of rats exposed acutely or subchronically to acetochlor favours
      a non-genotoxic mechanism for the induction of these adenomas. The observation of
      a time- and dose-related increase in S-phase cells in the nasal epithelium is
      consistent with this conclusion. Despite some confusion caused by the early use
      of perilethal gavage administrations of acetochlor to rodents, and supra-MTD
      dietary concentrations in some of the chronic studies, the available MTD data are
      consistent with acetochlor not posing a genetic or carcinogenic hazard to humans.

PMID- 8880208
TI  - Spermatotoxic effects of carbaryl in rats.
AB  - The spermatotoxic effect of carbaryl in adult and young male rats has been
      examined. Carbaryl 50 and 100 mg/kg b.wt. Male fed 5 d/week for 60 days, caused
      dose and age-dependent decline in epididymal sperm count and sperm motility, an
      increase in sperm with abnormal morphology. The dose of 25 mg/kg/d was a 'No
      observed effect level' for the indices studied. Young animals in comparison to
      adults exhibited pronounced spermatotoxic effects.

PMID- 8880209
TI  - Carcinogens in food: priorities for regulatory action.
AB  - A pragmatic possible approach to the prioritization of chemical carcinogens
      occurring as food contaminants is described, based on the carcinogenic risk to
      the population. This should be of value in ensuring that resources for assessment
      and management of carcinogens in food are directed to the most important areas
      with regard to carcinogenic risk to the population. Key components of this
      approach are an assessment of the carcinogenic hazard to humans combined with
      estimations of intakes per person and of the proportion of the population
      exposed. These are used to derive an index referred to as the Population
      Carcinogenic Index. Concerning the hazard assessment expert judgement is used to
      place the chemical in one of five categories. The highest category is for
      chemical carcinogens that are believed to act by a genotoxic mechanism. It is
      recognised that such compounds may vary enormously with respect to their potency
      and various approaches to ranking carcinogens on the basis of potency are
      reviewed. The approach adopted is to subdivide the genotoxic carcinogens category
      into high, medium and low potency based on the TD50 value. Methods of estimating
      intakes and exposed populations are considered and an approach which groups these
      into broad categories is developed. The hazard and exposure assessments are then
      combined to derive the Population Carcinogenicity Index.

PMID- 8880210
TI  - Potential dangers from topical preparations containing methyl salicylate.
AB  - Methyl salicylate (oil of wintergreen) is widely available in many over-the
      counter liniments, ointments, lotions or medicated oils for the relief of
      musculoskeletal aches and pains. Ingestion of methyl salicylate poses the threat
      of severe, rapid-onset salicylate poisoning because of its liquid, concentrated
      form and lipid solubility. Excessive usage of these preparations in patients
      receiving warfarin may result in adverse interactions and bleedings. Methyl
      salicylate in topical analgesic preparations may cause irritant or allergic
      contact dermatitis and anaphylactic reactions. Physicians should fully appreciate
      the potential dangers from topical preparations containing methyl salicylate.

PMID- 8880211
TI  - Pharmacological-toxicological expert report. CAELYX. (Stealth liposomal
      doxorubicin HCl).

PMID- 8880212
TI  - Isotype-directed enrichment of B cells by magnetic beads in the generation of
      immunoreactive human monoclonal antibodies.
AB  - Pooled lymphocytes collected from cancer patients were mixed with a biotinylated
      murine MAb specific to human IgG4. To this were added streptavidin-conjugated
      magnetic beads. After magnetically separating the bead-lymphocyte complex, the B
      cells were washed and fused with the WIL-2 derived human fusion partner, SHFP-1.
      Subsequently derived human-human hybridomas were screened for IgG4
      immunoreactivity to target tumor cell lines. Several hybridomas reacted with a
      variety of malignant cell types, including melanoma, neuroblastoma, and
      pancreatic tumor cells. One hybridoma in particular, designated SC-GM4,
      recognized an antigen by Western blot with an apparent molecular weight of 57
      kDa. This facile approach of magnetically separating selected populations of
      lymphocytes should be relatively simple to apply to other antigens and antibodies
      to preselect the type, class, and properties of the desired MAb.

PMID- 8880213
TI  - Two spatially distant epitopes of human lactoferrin.
AB  - Lactoferrin (LF) is an iron binding protein, which may represent a target for
      antineutrophil cytoplasmic antibodies (ANCA) in patients affected by rheumatoid
      arthritis, ulcerative colitis, and primary sclerosing cholangitis. Here we
      describe the production and characterization of two new monoclonal antibodies
      (MAbs) against human LF. These MAbs (AGM 10.14, an IgG1, and AGM 2.29, an IgG2b)
      recognize spatially distant epitopes of LF as assessed by cross-blocking
      experiments. We also demonstrated by indirect immunofluorescence that both MAbs
      react with ethanol-fixed neutrophil granulocytes showing a perinuclear staining
      pattern. AGM 2.29 and AGM 10.14 have been utilized as capture and labeled tracer
      antibody, respectively, in a double determinant immunoassay (DDIA) to measure
      soluble LF. The results obtained show that this DDIA allows us to quantify even
      low concentrations of LF, the maximal range of the assay sensitivity being
      between 12 and 780 ng/ml. Therefore, AGM 10.14 and AGM 2.29 may represent useful
      reagents for studying the role of autoantibodies to LF as well as for measuring
      soluble LF, which is a reliable secretory marker of neutrophil activation.

PMID- 8880214
TI  - A monoclonal antibody that recognizes a 110-kDa protein primarily located on the
      platelet alpha-granule, which is translocated to and upgraded on the surface
      membrane of platelets upon activation.
AB  - A murine monoclonal antibody, designated as MAb AAP2, was produced by immunizing
      human activated platelets to BALB/c mice. MAb AAP2 recognizes a platelet membrane
      antigen that was present in trace amount on the membrane of resting platelets,
      and was strongly expressed on the membrane after activation with thrombin as
      demonstrated by immunofluorescence microscopy. Platelet granule fractionation by
      ultracentrifugation on sucrose density gradient and metrizamide showed that the
      target antigen of MAb AAP2 was located in alpha-granules but not in lysosomes or
      dense granules. On Western blot prepared with whole platelet lysate, MAb AAP2
      bound to a 110-kDa protein under nonreducing and reducing conditions. These
      results suggest that MAb AAP2 recognizes a 110-kDa platelet antigen, which is
      primarily located on the alpha granule of platelets and translocated to and
      upgraded on the surface membrane upon activation.

PMID- 8880215
TI  - A novel monoclonal antibody, L1A3, is directed to the functional site of the
      alpha v integrin subunit.
AB  - We have generated a monoclonal antibody (MAb) L1A3 directed to the alpha v
      integrin subunit as shown by competitive binding with other anti-alpha v-specific
      MAbs and immunodepletion. MAb L1A3 is a function-blocking antibody inhibiting
      cell adhesion to the extracellular matrix proteins, fibronectin and vitronectin.
      Adherence to vitronectin of all cells studied including normal dermal
      microvascular endothelial cells and three tumor cell lines was inhibited in the
      presence of MAb L1A3. However, the contribution of the alpha v integrin subunit
      in mediating adhesion to fibronectin was dependent on the cell line, as indicated
      by differences in the inhibition of cell adhesion with MAb L1A3 and alpha 5 beta
      1 integrin subunit blocking MAb P1D6. Glioma U251.3 cell adhesion to fibronectin
      was blocked by either MAb L1A3 or MAb P1D6 while fibrosarcoma HT1080 cells were
      blocked with MAb P1D6 only. Tumor cell migration mediated by vitronectin and
      fibronectin is blocked by MAb L1A3 in the two-dimensional spheroid outgrowth
      assay. Microvascular endothelial cell transwell membrane migration onto the
      fibronectin was also blocked by MAb L1A3. Comparison of the integrins involved in
      U251.3 cell migration on fibronectin or tenascin using a panel of integrin
      blocking MAbs including MAb L1A3 showed that only a subset of integrins
      participating in cell adhesion is essential for cell migration and these
      integrins appear to be ligand specific. Fibronectin-mediated tumor cell migration
      was critically dependent on alpha v integrins as shown by L1A3 blocking of
      migration while the beta 1 integrins were absolutely necessary for tenascin
      mediated cell migration.

PMID- 8880216
TI  - Generation and application of monoclonal antibody to human pancreatic carcinoma.
AB  - An IgG1 mouse monoclonal antibody (MAb) YPC3 against human pancreatic carcinoma
      was generated by a hybridoma technique. When human tissue sections were examined
      with immunohistochemical staining, YPC3 MAb reacted with 28 of 32 (87.5%) cases
      of pancreatic carcinoma tissue; it failed to react with all 11 cases of normal
      pancreas examined. When 99mTC-radiolabeled YPC3 MAb was administrated
      intravenously to the nude mice bearing xenograft of pancreatic carcinoma, clear
      scintigraphic visualization of tumor xenograft was found with SPECT 24 h after
      injection. Administration of either YPC3 MAb or LAK cells combined with YPC3 MAb
      could inhibit the growth of the xenografts in nude mice. These results suggest
      that YPC3 MAb might be an ideal carrier for radioimmunolocalization and
      immunotherapy of human pancreatic carcinoma.

PMID- 8880217
TI  - Establishment of monoclonal antibodies against human erythrocyte NADH-cytochrome
      b5 reductase.
AB  - NADH-cytochrome b5 reductase (b5R) is a multifunctional redox enzyme, whose
      deficiency leads to hereditary methemoglobinemia. By using recombinant human red
      cell b5R as antigen to immunize BALB/c mice and conventional cell fusion, we have
      established two mouse hybridoma cell lines secreting IgG monoclonal antibodies
      (MAbs) to b5R. In immunoblotting, the MAbs were shown to react specifically with
      b5R. They were also found to be capable of capturing b5R activity from b5R
      solution and normal human hemolysate. It was implied that the binding sites of
      the MAbs might not be proximal to the active site of the enzyme, but might be in
      close proximity to each other. The MAbs will be useful in b5R-related
      investigations.

PMID- 8880219
TI  - Anti-IRS-1 monoclonal antibody, 6G5, cross-reacts to IRS-2.
AB  - We previously reported the production of anti-IRS-1 monoclonal antibodies against
      human IRS-1 C-terminal portion. One of anti IRS-1 monoclonal antibodies, 6G5, was
      found to immunologically cross-react with IRS-2, which has been reported
      recently. The data presented here provide information arising from the use of the
      anti-IRS-1 MAb, 6G5; this MAb was found to be a useful reagent in studying the
      functional role of IRSs in the insulin-signaling system.

PMID- 8880218
TI  - Construction of a sensitive enzyme immunoassay for human fibroblast growth factor
      9.
AB  - Hybridomas secreting monoclonal antibodies (MAbs) against human fibroblast growth
      factor 9 (FGF-9) were established using recombinant human (rh) FGF-9 N33 as the
      immunogen. Among these, MAb 150-59 demonstrated a potent neutralizing activity
      against FGF-9. It arrested the FGF-9-induced growth of BALB/c 3T3 A31 cells at an
      equimolar dose of the factor. It also abrogated the in vivo thrombopoietic
      activity of FGF-9. Mitogenic activity of several other FGF family members such as
      FGF-1, FGF-2, and FGF-4 was not neutralized by this MAb. A sensitive sandwich
      enzyme immunoassay for FGF-9 was developed employing MAbs 150-59 and 13-3. The
      detection limit of this system was 3 pg/well. In this assay system, FGF-1 and FGF
      2 were not cross-reactive up to 1 microgram/well. Using this system, the
      distribution of FGF-9 in rat organs was examined. FGF-9 could be detected only in
      the extract of rat cerebellum. Also, we detected a high amount of FGF-9 in the
      culture supernatant of certain cell lines originated from human tumor. These
      findings suggest that this enzyme immunoassay system may be used to clarify
      biological meaning of FGF-9.

PMID- 8880220
TI  - Recombinant human prolactin induces protection against Salmonella typhimurium
      infection in the mouse: role of nitric oxide.
AB  - In the present study, we demonstrated that repeated treatment with recombinant
      human prolactin (rhPRL) protected mice against Salmonella typhimurium infection.
      The protective activity was statistically significant, dose-dependent and present
      only when rhPRL treatments were performed before the infection. This activity was
      probably related to the observed increases in phagocytosis and intracellular
      killing of peritoneal macrophages induced by the hormonal treatment. The number
      of peripheral leukocytes was not modified, excluding a mobilization of cells from
      other compartments. A decrease in the mortality rate after challenge was also
      observed in mice treated with the monoclonal antibody anti-PRL receptor U5,
      confirming that the protective activity was associated with receptor activation.
      Our studies also suggest that nitric oxide (NO) production was involved in the
      protective effect of rhPRL since pre-treatment of the animals with L-NAME, an
      inhibitor of NO-synthase, was able to completely revert the protective activity,
      whereas D-NAME, the inactive D-isomer, was without effect.

PMID- 8880221
TI  - Mirfentanil antagonizes morphine-induced suppression of splenic NK activity in
      mice.
AB  - Mirfentanil [N-(2-pyrazinyl)-N-(1-phenethyl-4-piperidinyl)-2-furamide] was
      studied for its antinociceptive and immunomodulatory effects in mice Mirfentanil
      (1.0-32.0 mg/kg) increased tail-flick latency to a thermal stimulus and this
      effect was antagonized (94 +/- 2%) by naltrexone (10.0 mg/kg). Unlike naltrexone,
      the delta opioid selective antagonist naltrindole (20.0 mg/kg) had no effect on
      mirfentanil-induced analgesia. In a dose-dependent fashion, the mu-selective
      antagonists beta-funaltrexamine (1.0-40.0 mg/kg) and naloxonazine (1.0-35.0
      mg/kg) blocked mirfentanil (10.0 mg/kg)-induced analgesia up to 75% of the
      maximum analgesic effect. Norbinaltorphimine (10.0 mg/kg) partially blocked (35%)
      the maximum analgesic effect following mirfentanil (10.0 mg/kg) administration.
      Single doses of mirfentanil (0.1-32.0 mg/kg) had no effect on splenic NK
      activity. However, preadministration of mirfentanil (1.0-10.0 mg/kg) blocked
      morphine-induced suppression of splenic NK activity. Collectively, the results
      suggest that mirfentanil is a novel opioid that induces antinociception
      predominately through mu opioid receptors but, unlike morphine or fentanyl, does
      not suppress splenic NK activity.

PMID- 8880222
TI  - Immunomodulating and articular protecting activities of a new anti-rheumatic
      drug, TAK-603.
AB  - We investigated the pharmacological activities of a newly synthesized anti
      rheumatic drug, TAK-603. (1) In vivo: In adjuvant arthritic (AA) rats, TAK-603
      inhibited the hind paw swelling and the body weight loss. The minimum effective
      dose was 3.13 mg/kg/day (p.o.). Histological and radiographic studies showed that
      TAK-603 suppressed the development of synovial lesions and joint and bone
      destruction. TAK-603 was also effective in AA rats when administered for the
      first 7 days after the adjuvant injection. It suppressed type IV allergy (25
      mg/kg/day, p.o.) but had no effect on type III allergy. It had little effect in
      acute inflammation, analgesic and antipyretic models. These data suggest that TAK
      603 acts on the immune system, especially on cellular immunity. (2) In vitro: TAK
      603 suppressed the mitogen-induced proliferation of mouse lymphocytes and the
      ConA-induced IFN-gamma and IL-2 production by rat lymphocytes at 10(-7) to 10(-5)
      M. It also significantly inhibited the IL-1 induced extracellular matrix
      reduction in rabbit chondrocytes. It had no effects on prostaglandin E2 (PGE2)
      production in rat peritoneal cells. These data show that TAK-603 has the ability
      to suppress the immune system and protect cartilage from destruction. TAK-603 is
      expected to be a promising drug for rheumatoid arthritis.

PMID- 8880223
TI  - Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human
      blood monocytes and IL-2 and interferon-gamma in T cells.
AB  - Tricyclic antidepressants (TCAs) are widely used in treating depressive
      disorders. It has been demonstrated that, for instance, IL-1 beta and IL-6
      inhibit the HPA axis, which plays a role in the development of depressions.
      Therefore. we were interested in investigating how TCAs influence cytokine
      release by T lymphocytes and monocytes respectively. Cells were incubated with
      either 5 microM clomipramine, 15 microM imipramine or 20 microM citalopram. IL-2
      release was suppressed to 60% of the control values by clomipramine and
      imipramine (p = 0.001; p = 0.000), but citalopram was found to cause a much
      weaker inhibition (only 18%) (p = 0.16). INF-gamma release was affected to a
      lower degree than IL-2 release, and imipramine (34%) (p = 0.054) was more potent
      than clomipramine (24%) (p = 0.16) and citalopram (12%) (p = 0.059) in this case.
      Monocytes incubated with TCA for 4 h exhibited only limited inhibition of IL-1
      beta and IL-6 release, i.e., 6-25% for all three compounds. The corresponding
      value for TNF-alpha release was 20-45% inhibition, with citalopram being the
      weakest inhibitor. After 10 h of monocytes to LPS exposure, all three compounds
      exerted a strong inhibition of IL-1 beta and TNF-alpha release, i.e., 60-70% with
      p-values below 0.012 for all of them. However the inhibition of IL-6 release was
      less than 35%. Citalopram was equality as potent as imipramine and clomipramine
      in inhibiting IL-6 release after long-term exposure of monocytes to LPS. All
      three TCAs elevated intracellular cAMP concentrations significantly in T
      lymphocytes and monocytes (p < 0.001).

PMID- 8880224
TI  - Facilitation of apoptosis by autologous serum and related immunosuppression in
      the splenocyte culture.
AB  - The addition of adult mouse serum (MS) to the culture of mouse splenocytes
      resulted in an accelerated decrease of viable cell number during initial 24 h of
      culture as determined by the trypan blue dye exclusion test and the propidium
      iodide staining method. Furthermore, the extent of DNA fragmentation, the
      hallmark of apoptosis, determined by agarose gel electrophoresis and the amount
      of fragmented DNA measured by ELISA method showed that the extent of apoptosis
      was clearly increased in splenocytes cultured in the presence of MS. Under the
      scanning and transmission electron microscopic observations, the large portion of
      splenocytes showed morphological characteristics of apoptotic cells such as
      apoptotic body, condensed chromatin and shrunken appearance. With the accelerated
      rate of apoptosis, the immunocompetence of splenocytes such as the antibody
      production, natural killer cell activity, and proliferation by mitogens was
      strongly suppressed. When analyzed by surface immunolabelling flow cytometry, the
      subsets of lymphocytes (B, T, CD4+T and CD8+T cells) were affected in a global
      non-selective manner. As determined by ultrafiltration, the molecular weights of
      apoptosis-facilitating factors present in MS appeared to be greater than 10 kDa.
      Upon fractionation with Sephadex G-200, the apoptotic factors were separated into
      2 fractions. In summary, results obtained in the present study indicate that some
      unidentified endogeneous macromolecules present in MS may produce the stimulatory
      effect on the apoptosis and cause immunosuppression of splenocytes under culture.

PMID- 8880225
TI  - Effects of different inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase, pravastatin sodium and simvastatin, on sterol synthesis and
      immunological functions in human lymphocytes in vitro.
AB  - It has been shown previously that 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (HMG-CoA RIs) such as compactin and lovastatin suppress human
      lymphocyte functions in vitro (Cuthbert and Lipsky, 1981; Cutts and Bankhurst,
      1989). Although it is not fully understood what inhibitory role the HMG-CoA RIs
      perform in causing this suppression, we show in this study that a certain
      inhibition threshold (inhibition level > 90%) of lymphocytic HMG-CoA reductase is
      required for the HMG-CoA RIs to attain effective inhibitory action in human
      lymphocyte lymphocyte functions in vitro. Thus the inhibitory activity of
      simvastatin, a lipophilic inhibitor, on sterol synthesis (HMG-CoA reductase
      activity) in lymphocytes was as much as 430 times more potent than that of
      pravastatin sodium, a hydrophilic inhibitor (IC50; 0.013 microM and 5.6 microM,
      respectively), and although pravastatin sodium and simvastatin at concentration
      levels of 10 and 0.016 microM respectively, inhibited the sterol synthesis in
      just over 50%, they failed to inhibit the lymphocyte functions. Significant
      inhibition (P < 0.01) of lymphocyte functions, including lymphocyte proliferative
      response to a variety of stimuli and activated natural killer-cell cytotoxicity,
      was demonstrated only when greater than 90% of the sterol synthesis in
      lymphocytes was inhibited by either simvastatin or simvastatin sodium salt at
      concentrations above 2 microM. This simvastatin-induced inhibition of lymphocyte
      functions was almost completely reversed by the addition of a 1 mM solution of
      mevalonate. Although simvastatin at a lower clinical blood concentration of 0.016
      microM failed to inhibit either lymphocyte functions or HMG-CoA reductase
      activity sufficiently, at this level it caused a significant increase in
      cyclosporin A-induced suppression of T-cell response. These results infer that
      insufficient inhibition (in the 50% region) of HMG-CoA reductase activity by a
      low clinical blood concentration of HMG-CoA RIs, could still render the
      lymphocytes susceptible to immunosuppressive treatments. Pravastatin sodium on
      the other hand, is inactive in inhibiting lymphocyte functions in vitro, and such
      inactivity can be explained solely of the basis of its failure to inhibit HMG-CoA
      reductase activity in lymphocytes sufficiently.

PMID- 8880226
TI  - Dexamethasone or cyclosporin A inhibits stem cell factor-dependent secretory
      responses of rat peritoneal mast cells in vitro.
AB  - Stem cell factor (SCF) is potent activator of degranulation of rat peritoneal
      mast cells in vitro and may promote mast cell activation under certain
      circumstances in vivo. In this study we report that the anti-inflammatory
      glucocorticoid dexamethasone (DEX) and the immunosuppressive cyclosporin A (CsA)
      are both effective inhibitors of SCF-induced degranulation of rat peritoneal mast
      cells in vitro, measured as release of serotonin (5-HT). Of the two drugs, DEX
      was the more potent with near maximal inhibition reached at 10(-8) M, whereas a
      graded inhibition was seen with CsA in the range 10(-8)-10(-6) M. DEX was equally
      effective in inhibiting the release of 5-HT induced by either SCF or anti-IgE,
      but was less effective in inhibiting release induced by compound 48/80 or calcium
      ionophore A23187. CsA produced a similar degree of inhibition of degranulation
      induced by SCF, anti-IgE or ionophore, but was without effect on the response to
      compound 48/80. Neither DEX nor CsA had any significant effect on mast cell
      surface expression of the SCF receptor or IgE antibody. We conclude that both DEX
      and CsA inhibit components of the secretion-coupling pathways that are triggered
      following either SCF receptor engagement or cross-linking of IgE, but that these
      drug differentially influence mast cell secretion induced by compound 48/80 or
      the calcium ionophore A23187.

PMID- 8880227
TI  - Dumpster diving in sharps disposal containers: what's really inside?

PMID- 8880228
TI  - Reducing occupational exposure to bloodborne pathogens: where do we stand a
      decade later?

PMID- 8880229
TI  - Risk factors for mortality associated with enterococcal bloodstream infections.
AB  - OBJECTIVE: To determine risk factors for mortality in patients with a nosocomial
      enterococcal primary bloodstream infection (EPBI) and to assess whether
      vancomycin resistance placed a patient at increased risk of death.
      DESIGN/SETTING: A retrospective cohort study was conducted in four National
      Nosocomial Infection Surveillance System hospitals. RESULTS: Of 145 patients
      identified with EPBIs, 74 (51%) died, and 26 (18%) had a vancomycin-resistant
      isolate. Upon comparing patients with EPBIs who survived to those who died, no
      associations were found between mortality and prior invasive device use,
      procedure history, type or number of prior nosocomial infections, length of
      hospitalization before infection, or receipt of vancomycin. Independent
      predictors of mortality were indices of severity of illness (APACHE II score and
      comorbidity weighted index), age, the use of third-generation cephalosporins or
      metronidazole during the week prior to infection, and female gender. CONCLUSIONS:
      Vancomycin resistance was not an independent predictor of death, and its role was
      difficult to establish, because cohort patients were among the most severely ill
      of all hospitalized patients. Enterococcal primary bloodstream infections appear
      to indicate severe, lifethreatening disease processes. The pathogenicity of
      enterococci and the role of vancomycin resistance as a cause of mortality in
      patients with EPBIs need to be assessed further.

PMID- 8880230
TI  - Rapid identification of respiratory viruses: impact on isolation practices and
      transmission among immunocompromised pediatric patients.
AB  - OBJECTIVE: To determine whether empiric isolation of patients with acute
      respiratory virus infection symptoms could be discontinued when preliminary shell
      vial cultures were negative, and the impact of this approach on hospital
      resources. DESIGN: In 1993, we retrospectively reviewed respiratory virus test
      results from 1992 to 1993 and extended data collection prospectively through the
      1993 to 1994 season. The rapid test and 48-hour shell vial results were compared
      to a standard of rapid test plus 5-day shell vial culture results to determine
      the sensitivity and specificity of these "preliminary" results. SETTING: A 400
      bed tertiary referral research hospital. PATIENTS: Patients from any inpatient
      unit or clinic with acute respiratory virus infection symptoms who had a specimen
      submitted for respiratory virus culture. Patients were placed on empiric
      respiratory isolation pending culture results. RESULTS: The overall sensitivity
      of the combined rapid and 48-hour culture results in adults and children was 97%.
      All 15 pediatric patients with respiratory syncytial virus infection who had
      specimens submitted on first suspicion of respiratory virus infection were
      positive by rapid test. Culture results were positive within 48 hours for 100% of
      patients with influenza A (15 patients), influenza B (6), and parainfluenza (18)
      viruses. Of 59 pediatric inpatients who were isolated empirically awaiting 5-day
      culture results, 31 (52%) ultimately were determined to be culture negative.
      CONCLUSIONS: Empiric isolation of symptomatic children can be discontinued at 48
      hours when both the rapid test and the early culture results are negative. Our
      institution would have saved 93 days of unnecessary isolation over 2 years had
      such a policy been in place.

PMID- 8880231
TI  - An outbreak of viral gastroenteritis in a nursing home: importance of excluding
      ill employees.
AB  - BACKGROUND: In May 1994, 43 persons in a nursing home were reported with
      gastroenteritis. An outbreak investigation was conducted to determine risk
      factors for gastroenteritis among residents and staff. METHODS: Data were
      analyzed using contingency tables; relative risks (RR) and statistical
      significance were determined with Fisher's Exact Test. The chi-squared statistic
      to perform a goodness of fit test for the binomial distribution was used to
      determine whether cases occurred randomly and independently of each other. Stools
      were tested for bacterial enteric pathogens, ova, and parasites and were examined
      by electron microscopy, Southern hybridization, and reverse transcription
      polymerase chain reaction. Paired sera were collected to detect fourfold rises in
      antibody titer by enzyme immunoassay against Norwalk viruses. RESULTS: Of 121
      residents, 62 (51%) had gastroenteritis, as did 64 (47%) of the 136 staff. The
      index case was a nurse who became ill at work and continued to work, while
      symptomatic, for another 2 days. Only residents who had received medications from
      this nurse between May 17 and May 20 became ill on the first day of the outbreak
      (13 of 35 versus 0 of 5). Nurses and nurse aides were more likely than employees
      without direct resident contact to be cases (46 of 68 versus 18 of 58; RR, 2.18;
      P < .001). Bacterial stool cultures and parasite examinations were negative.
      Results of electron microscopy, polymerase chain reaction with Southern
      hybridization, and enzyme immunoassay indicated the causative agent was a small,
      round, structured virus similar to the Snow Mountain Agent. CONCLUSION: To
      minimize outbreaks in nursing homes, we recommend that ill staff be excluded from
      work until symptoms resolve.

PMID- 8880232
TI  - Initial worker evaluation of a new safety syringe.
AB  - A prospective evaluation of a new safety syringe requiring a one-step activation
      was carried out at the University of California, San Diego Medical Center. Only
      59.5% of 390 syringes were activated, and user acceptance and satisfaction were
      unfavorable. The development of safety devices should incorporate passive
      activation and take end-user satisfaction into consideration.

PMID- 8880233
TI  - Epidemiologic typing systems.
AB  - Microbial strain typing is a useful adjunct to clinical epidemiology. Phenotypic
      typing systems examine expressed characteristics, whereas genotypic systems,
      including recent PCR-based systems, examine chromosomal or plasmid DNA. Typing
      systems have evaluated bacteria, fungi, and viruses successfully. The criteria
      used to assess the utility of each system include typeability, reproducibility,
      and discriminatory power.

PMID- 8880234
TI  - Exploratory data analysis: data visualization or torture?
AB  - Exploratory Data Analysis offers a set of graphical and statistical tools to find
      the full meaning from data sets. The user visualizes, analyzes, and transforms
      data distributions with these tools. Graphs reveal relationships between
      variables; the residuals left after fitting data show the adequacy of the model.
      Without this careful examination and understanding of the data, rote data
      analysis using standard statistical tests can give misleading results.
      Exploratory Data Analysis has its own set of pitfalls and must be used with
      confirmatory statistics and studies. Increasing power and resolution in personal
      computers enables modern statistical software to make these methods widely
      accessible. By easily moving between data and their graphic representation,
      analysis can be comprehensive without being tedious. Exploratory Data Analysis
      can add an exciting and useful tool to the epidemiologist's repertoire. This
      article illustrates several tools from an evolving list.

PMID- 8880235
TI  - Surgical outcome information and the media.
AB  - There is increased media attention to healthcare outcome in the current reform
      atmosphere. Surgical care is a natural target for both print and electronic
      coverage. Hospital public relations departments often will be the interface with
      media representatives. Because surgical care outcome interpretation requires
      thoughtful evaluation of both single-patient and grouped-patient data, as well as
      knowledge of realistic risk-benefit ratios, it always is prudent to work with
      your local surgeon when the request for a story comes to the public relations
      department.

PMID- 8880236
TI  - Prevention and control of nosocomial infections in Spain: current problems and
      future trends.
AB  - Spain is a state member of the European Union, with more than 180,000 hospital
      beds and 800 public and private institutions. Only 6.9% of our gross national
      product is devoted to health expenditures. All citizens receive free health care
      through the National Health System. This system has given increasing attention to
      the prevention and control of nosocomial infections since 1986. In this article,
      results of serial prevalence surveys of antibiotic use and resistance patterns of
      microorganisms isolated from nosocomial infections are discussed. The needs for
      future development of infection control and quality assurance training programs
      in Spain also are discussed. Overall, a clinically and epidemiologically oriented
      approach to infection control is preferred, with greater emphasis in the role of
      infection control practitioners and infection control committees.

PMID- 8880237
TI  - Serum and erythrocyte magnesium in critically ill patients?

PMID- 8880238
TI  - Serum and erythrocyte magnesium in critically ill patients.
AB  - OBJECTIVES: To evaluate the prevalence of serum and erythrocyte magnesium (Mg)
      abnormalities in patients on admission to the intensive care unit (ICU) and to
      test the hypothesis that low levels of Mg are associated with a higher mortality.
      DESIGN: Prospective study. SETTING: 14-bed ICU in a 1000-bed teaching hospital.
      PATIENTS: 179 consecutive patients admitted over a 4-month period. MEASUREMENTS:
      Total serum Mg (Mgs) and erythrocyte Mg (Mge) were determined on admission by
      atomic absorption spectrophotometry. Severity of illness was assessed by Acute
      Physiology and Chronic Health Evaluation (APACHE) II and the number of organ
      system failures (OSF) during the first 24 h. The patients were followed up until
      discharge from hospital. MAIN RESULTS: On admission, 79 patients (44%) were
      hypomagnesemic and 10 (6%) were hypermagnesemic. A low level of Mge was observed
      in 119 patients (66%). In patients with similar APACHE II scores and OSF numbers,
      more of those with hyperMgs died during their ICU stay. However, the Mge value on
      admission did not correlate with patient outcome. CONCLUSIONS: We confirm the
      high prevalence of Mgs abnormalities as well as Mg deficiency on admission to a
      medical ICU. Low levels of Mgs and Mge are not associated with higher fatality.
      HyperMgs was associated with patient death.

PMID- 8880239
TI  - Response to nitric oxide inhalation in early acute lung injury.
AB  - OBJECTIVE: To evaluate the dose response of inhaled nitric oxide (NO) on gas
      exchange and central haemodynamics in patients with early acute lung injury
      (ALI). DESIGN: Prospective, multicentre clinical study. SETTING: General ICUs in
      university and regional hospitals. PATIENTS: 18 Patients with early ALI according
      to specified criteria. INTERVENTIONS: During controlled ventilation an inhalation
      system was used to deliver NO (1000 ppm in N2) and O2/air to the low pressure
      fresh gas inlet of a Siemens 900C ventilator. Haemodynamics and pulmonary gas
      exchange variables were measured at baseline and at stepwise increased
      inspiratory NO concentrations of 0.1, 0.3, 1, 3, 10, 30 and 100 ppm, each dose
      being maintained for 15 min. Dose testing was repeated the next day, and the
      response to prolonged (2 h) NO inhalation at 1 and 10 ppm was also tested.
      MEASUREMENTS AND RESULTS: Inhalation of NO produced a significant increase in
      PaO2 (P < 0.0025). The degree of response, as well as the optimal NO dose varied
      in individual patients and between different days. Venous admixture (QVA/QT) was
      reduced (P < 0.02) from 38% (31-46%) to 33% (26-41%). In our patients with early
      acute lung injury and only a moderate elevation in pulmonary arterial pressure NO
      inhalation did not reduce mean pulmonary artery pressure significantly, being
      27.0 (21-30) mmHg at baseline and 26.0 (21-30) mm Hg at 100 ppm. CONCLUSIONS:
      This study shows that improvements in arterial oxygenation in response to inhaled
      NO may show great inter- as well as intraindividual variability, and that
      improvements in arterial oxygenation occur without any measurable lowering of the
      pulmonary artery pressure.

PMID- 8880240
TI  - Early and late onset bacteremia have different risk factors in trauma patients.
AB  - OBJECTIVE: The aim of this study was to identify risk factors and to describe
      epidemiological patterns for early-(EOB) and late-onset bacteremias (LOB) after
      trauma. DESIGN: A prospective study conducted on 141 consecutive trauma patients.
      SETTING: A general intensive care unit (ICU) of a university hospital. PATIENTS:
      All multiple trauma patients admitted to our general intensive care unit (ICU)
      from December 1990 to May 1992 were prospectively enrolled in the study. The
      following information was collected for each patient and recorded in a computer
      database: demography, severity of trauma according to the Abbreviated Injury
      Scale (AIS), severity of coma according to the Glasgow Coma Scale (GCS), presence
      of pneumothorax, pulmonary contusion, rib fractures, hemothorax, and abdominal
      trauma, use of mechanical ventilation, and placement of central venous catheters.
      Bacteremias were defined as EOB when onset occurred within 96 h after trauma, and
      as LOB when appearing after 96 h from trauma. RESULTS: Thirty-seven patients
      developed bacteremia during their ICU stay (26%): 11 (29.7%) EOB and 26 (70.3%)
      LOB. Gram-positive cocci were isolated more frequently in EOB than in LOB (chi 2
      = 4.1, P = 0.04). The risk of EOB was significantly increased by the presence of
      pulmonary contusion [relative risk (RR) 15.0; confidence interval (CI) 1.99
      113.25], pneumonia before the onset of bacteremia (RR 3.56; CI 1.17-10.69), AIS
      score greater than 32 and an abdominal injury score greater than 9 (RR 3.11; CI
      1.02-9.49), while intravascular catheters and mechanical ventilation did not
      represent risk factors for EOB. LOB had a very different pattern and their risk
      was significantly increased by exposure to intravascular catheters (RR 4.96; CI
      1.23-19.94) and to mechanical ventilation lasting more than 7 days (RR 3.6; CI
      1.6-8.1). CONCLUSIONS: Scoring with the AIS of the abdominal and thoracic trauma
      at admission to the ICU appears a useful tool for identifying trauma patients at
      increased risk of EOB. A rigorous policy of catheter placement and maintenance as
      a means of reducing late bacteremias in trauma patients is essential.

PMID- 8880241
TI  - A randomized cross-over comparison of the hemodynamic response to intermittent
      hemodialysis and continuous hemofiltration in ICU patients with acute renal
      failure.
AB  - OBJECTIVE: To compare the hemodynamic response of ICU patients with acute renal
      failure of a 24-h continuous arteriovenous hemofiltration (CAVH) and that of
      patients with a 4-h intermittent hemodialysis (HD). DESIGN: Cross-over randomized
      clinical trial. The two periods to be compared were a 24-h CAVH and the 24-h
      encompassing a 4-h HD. These two periods were separated by a 24-h wash-out
      period. SETTING: Ten bed medicosurgical ICU of a tertiary care center in Paris,
      France. PATIENTS: Inclusion criterion was the requirement of replacement therapy
      for acute renal failure in patients already submitted to mechanical ventilation.
      INTERVENTIONS: CAVH was performed with Ringers' lactate used for restitution and
      infused before the hemofilter. The ultrafiltrate output was maintained at around
      15 ml/min. HD was performed with a bicarbonate-buffered dialysate. MEAN OUTCOME
      MEASURES: Mean arterial pressure (MAP), use of adrenergic drugs, and change in
      body weight during each period. RESULTS: Twenty-seven consecutive patients were
      included, 15 CAVH-HD and 12HD-CAVH. CAVH and HD allowed the same metabolic
      efficacy. No hemodynamic parameter (MAP, amount of adrenergic drugs, change in
      body weight) differed between the two methods. CONCLUSIONS: CAVH is equivalent to
      HD in terms of MAP and the use of vasopressive drugs and fluids. Establishing the
      superiority of CAVH would require carefully controlled studies assessing either
      outcome or changes in tissue oxygenation.

PMID- 8880242
TI  - Intermittent hemodialysis in critically ill patients with multiple organ
      dysfunction syndrome is associated with intestinal intramucosal acidosis.
AB  - OBJECTIVE: Conventional intermittent hemodialysis in the critically ill patient
      can be associated with hemodynamic and respiratory instability. Intermittent
      hemodialysis induced arterial hypotension might be detrimental. We therefore
      studied the influence of intermittent hemodialysis on systemic and regional
      oxygen transport in critically ill patients. DESIGN: Prospective descriptive
      study. SETTING: Medical/surgical 24-bed intensive care unit in a university
      hospital. PATIENTS: Eleven critically ill patients admitted to the intensive care
      unit (APACHE III score: 82 +/- 12) and developing multiple organ dysfunction
      syndrome with acute renal failure. All patients were mechanically ventilated and
      hemodynamically stable with inotropic support. Systemic oxygen transport
      variables were calculated, and arterial blood lactate concentration was measured
      before, during, and after intermittent hemodialysis. Tonometer PCO2 was measured
      using a tonometer, and arterial-tonometer CO2 gap was used as an indicator of
      intestinal intramucosal acidosis. RESULTS: Intermittent hemodialysis induced an
      increase in calculated systemic oxygen consumption (P < 0.01). During
      intermittent hemodialysis there was a significantly higher need of inotropic
      support (P < 0.05) to maintain arterial blood pressure, cardiac index, and
      calculated systemic arterial oxygen delivery. The arterial-tonometer CO2 gap
      increased significantly during and after the procedure. CONCLUSION: In critically
      ill patients with multiple organ dysfunction syndrome intermittent hemodialysis
      induces an increase in oxygen consumption. Despite higher inotropic support to
      maintain systemic calculated oxygen delivery intestinal intramucosal acidosis
      occurs during intermittent hemodialysis and may even persist after the procedure
      is terminated.

PMID- 8880243
TI  - Weaning and extubation in the intensive care unit. Clinical or index-driven
      approach?
AB  - OBJECTIVE: To assess the outcome of a clinical judgement-based approach to
      weaning and extubation and to adduce the predictive accuracy of various
      mechanical respiratory indices measured in parallel. DESIGN: Prospective study.
      SETTING: Multidisciplinary intensive care unit at a university teaching hospital.
      PATIENTS: 163 consecutive mechanically ventilated patients, excluding
      tracheotomy, for weaning trial and extubation. INTERVENTIONS: Using bedside
      clinical assessment, aided by arterial gas analysis, patients were weaned from
      mechanical ventilation to spontaneous ventilation via to continuous positive
      airway pressure (CPAP) circuit (with pressure support) of a microprocessor
      controlled ventilator. Extubation occurred from the CPAP circuit at 7 cmH2O
      pressure support, fractional inspired oxygen (FIO2) < or = 0.5 and CPAP level of
      < or = 5 cmH2O, such that the partial pressure of oxygen in arterial blood (PaO2)
      was > or = 65 mmHg. Before extubation, observation for a 1-h (T0 and T60) trial
      period allowed measurement of vital capacity (VC), expired minute volume (VE),
      respiratory rate/tidal volume (f/VT) and maximal inspiratory pressure (MIP) using
      a one-way valve technique over 25 s. MEASUREMENTS AND MAIN RESULTS: Over 7
      months, 163 patients (62 females and 101 males; mean (SD) age 64(15) years) were
      considered. There were 91 surgical (18 with chronic obstructive pulmonary
      disease; COPD) and 72 medical (28 with COPD) patients. Ventilation was for > or =
      1 day (median 5 days, range 1-31) in 115 [group I; APACHE II score 23(8)] and <
      or = 1 day in 48 [Group II; APACHE II score 17(6)]. Three patients (all Group I:
      2 surgical, 1 medical) were reintubated within 24 h, an overall extubation
      failure rate of 1.8%. In group I, at T0, PaO2/FIO2 was 238(65), f/VT 50(26), MIP
      44(21) cmH2O, VE 10.6(3.7) l/min, VC 13(5) ml/kg. Cardiorespiratory variables did
      not change significantly in either group, T0 to T60. For prediction of
      reintubation (n = 163), only VE (threshold > 10 l/min) and f/VT (threshold > 100)
      demonstrated moderate sensitivity and specificity at T60: 67 and 52% and 33 and
      94%, respectively. CONCLUSIONS: Bedside clinical judgement of weaning and
      extubation produces satisfactory outcomes. As a routine, mechanical predictive
      indices have limited utility.

PMID- 8880244
TI  - Cleavage of plasma high molecular weight kininogen in surgical ICU patients.
AB  - OBJECTIVE: To characterize kininogens in plasma from surgical patients in the
      intensive care unit (ICU). DESIGN: Prospective study. SETTING: Surgical ICU.
      PATIENTS: 35 patients aged 19-79 years, divided into two groups: sepsis (defined
      by standard criteria) and nonsepsis. MEASUREMENTS AND RESULTS: Studies of
      proteolytic degradation of H-kininogen showed degradation in both patient groups
      compared to healthy controls. Functional quantification of prekallikrein showed a
      reduction of prekallikrein in plasma from both patients groups. Functional
      quantification of kininogens by a cysteine proteinase inhibitor assay showed no
      significant differences between the patients and the controls. Immunological
      levels of H-kininogen and total kininogen were not significantly different from
      normal plasma. No differences could be detected between the two patient groups in
      any of the parameters studied. CONCLUSIONS: This study showed that contact
      activation took place in surgical ICU patients: partial kinin release and
      consumption of prekallikrein took place in vivo.

PMID- 8880245
TI  - The influence of weight on stroke volume determination by means of impedance
      cardiography in cardiac surgery patients.
AB  - OBJECTIVES: Obesity is thought to be one of the conditions in which the impedance
      cardiographic method is less reliable for estimating stroke volume (SV). This led
      to the introduction of a weight correction factor, sigma, into the equation
      according to Sramek and Bernstein. However, no scientific evidence has been
      published to support the use of this factor. The objectives of the present study
      are to evaluate the influence of body weight on the accuracy of impedance
      cardiography and to validate Bernstein's weight correction factor by comparison
      with thermodilution in patients after coronary bypass surgery. DESIGN:
      Prospective clinical study. SETTING: A surgical intensive care unit in a
      university hospital. PATIENTS: 37 consecutive patients 24-36 h after coronary
      bypass surgery, sub-divided into a normal-weight group (n = 24), patients whose
      weight deviated less than 15% from their ideal weight, and an obese group (n =
      13), patients whose weight deviated more than 15% from their ideal weight.
      MEASUREMENTS: Kubicek's impedance cardiographic method and Sramek and Bernstein's
      method to assess SV are applied and compared to thermodilution. In order to study
      the validity of sigma, the results are compared between 24 patients with normal
      weight and 13 obese patients. RESULTS: A significant correlation between
      miscalculation of SV by impedance cardiography and the degree of obesity for
      Sramek and Bernstein's method is found when sigma is not included in the equation
      (r = -0.55, p < 0.05). This relation, however, remained significant when sigma
      was included in the equation (r = -0.40, p < 0.05). Kubicek's method shows no
      significant correlation for this relation (r = -0.30). Besides this, Sramek and
      Bernstein's method underestimates SV significantly in the obese group,
      independent of the use of sigma in the equation. These results are explained as
      being intrinsic to the equation, according to Sramek and Bernstein. In the whole
      group the impedance-derived SV did not significantly differ from SV as measured
      by means of thermodilution, independent of the method used to calculate SV.
      However, a considerably better correlation and agreement (mean difference +/- 2
      standard deviations is found when Kubicek's method is applied (r = 0.90, 0.5 +/-
      17.1 ml vs 0.64, -4.9 +/- 31.8 ml for Sramek and Bernstein's method).
      CONCLUSIONS: Weight significantly influences Sramek and Bernstein's method of
      impedance cardiography, whereas Kubicek's method is not biased by this factor.

PMID- 8880246
TI  - Right ventricular myocardial function in ARF patients. PEEP as a challenge for
      the right heart.
AB  - OBJECTIVE: To examine the hemodynamic effects of external positive end-expiratory
      pressure (PEEP) on right ventricular (RV) function in acute respiratory failure
      (ARF) patients. DESIGN: Prospective, with retrospective analysis on the basis of
      RV volume response to PEEP. SETTING: General intensive care unit in a university
      teaching hospital. PATIENTS: 20 mechanically ventilated ARF patients (mean lung
      injury score = 2.6 +/- 0.45 SD). INTERVENTION: Incremental levels of PEEP (0-5-10
      15 cmH2O) were applied and RV hemodynamics were studied by means of a Swan-Ganz
      catheter with a fast-response thermistor for right ventricular ejection fraction
      (RVEF) measurement. According to their response to PEEP 15, two groups of
      patients were defined: group A (9 patients) with unchanged or increased RV end
      diastolic volume index (RVEDVI) and group B (11 patients) with decreased RVEDVI.
      MEASUREMENTS AND RESULTS: At zero PEEP (ZEEP) the hemodynamic parameters of the
      two groups did not differ. In group A, cardiac index (CI) and stroke volume index
      (SI) decreased at all PEEP levels (5, 10, and 15 cmH2O), while RVEF started to
      decrease only at a PEEP of 10 cmH2O (-10.8%), and RVES(systolic)VI increased only
      at PEEP 15 cmH2O (+21.5%). RVEDVI was not affected by PEEP. In group B, CI and SI
      decreased at all PEEP levels (5, 10, and 15 cmH2O). Similarly, RVEDVI started to
      decrease at PEEP 5 cmH2O, while RVESVI decreased only at PEEP 15 cmH2O (-21.4%).
      RVEF was not affected by PEEP in this group. In each patient the slope of the
      relationship between RVEDVI and right ventricular stroke work index (RVSWI),
      expressing RV myocardial performance, was studied. This relationship was
      significant (no change in RV contractility) in 8 of 11 patients in group B and in
      only 2 patients in group A. In 4 patients in group A, PEEP shifted the
      RVSWI/RVEDVI ratio rightward in the plot, indicating a decrease in RV myocardial
      performance in these patients. CONCLUSIONS: PEEP affects RV function in ARF
      patients. The decrease in cardiac output is more often associated with a preload
      decrease and no change in RV contractility. On the other hand, the finding of
      increased RV volumes with PEEP may be associated with a reduction in RV
      myocardial performance. Thus, these results suggest that assessment of RV
      function by PEEP and preload recruitable stroke work may disclose otherwise
      unpredictable alterations in RV function.

PMID- 8880247
TI  - Analysis of P50 and oxygen transport in patients after cardiac surgery.
AB  - OBJECTIVE: To determine whether standard P50 after cardiac surgery decreases and
      whether decreased P50 is related to the transfusion of red blood cells (RBCs),
      acid-base changes, body temperature, oxygen parameters and/or duration of
      cardiopulmonary bypass (CPB). DESIGN: Pilot study in cardiac surgery patients.
      SETTING: University hospital. PATIENTS: 12 Consecutive elective cardiac surgery
      patients. INTERVENTIONS: Blood was taken before surgery, after CPB and in the
      intensive care unit until 18 h post-operatively. Cardiac output and oxygen
      consumption were measured. Buffy coat-poor RBCs were transfused, anticoagulated
      with citrate-phosphate-dextrose buffer and stored in saline-adenine-glucose
      mannitol at 4 degrees C, when haemoglobin was < 5.6 mmol.l-1. MEASUREMENTS AND
      RESULTS: Standard P50 was calculated from measured partial pressure of oxygen and
      of carbon dioxide, pH and oxygen saturation in mixed venous blood (SvO2) using
      the Severinghaus formula. Median length of RBC storage was 25 days. Standard P50
      after surgery was significantly lower than baseline value (p = 0.0001). The
      number of RBC units transfused and duration of CPB were conjointly associated
      with P50 (R2 = 0.72). Patients who received more RBCs consumed more oxygen.
      CONCLUSION: Cardiac surgery patients receiving more RBC units have lower standard
      P50 and consume more oxygen. P50 decreased more when the CPB took longer. Because
      a decrease in P50 implies a low ratio of mixed venous oxygen tension (PvO2) to
      SvO2, a shift in P50 should be taken into account when using SvO2 as a measure of
      global oxygen availability. When a direct measurement of SvO2 is not available,
      PvO2 should be used instead of calculated SvO2.

PMID- 8880248
TI  - Hypocholesterolemia and risk of death in the critically ill surgical patient.
AB  - OBJECTIVE: To evaluate the additional information provided by the determination
      of cholesterolemia to the Acute Physiology and Chronic Health Evaluation (APACHE)
      II score. DESIGN: Retrospective evaluation of patients admitted to the intensive
      care unit (ICU). SETTING: ICUs in a university hospital. PATIENTS: 638
      consecutive critically ill surgical patients. INTERVENTIONS: Surgical and medical
      therapy according to clinical status. MEASUREMENTS AND MAIN RESULTS: Two indices
      were devised: DELCUPOS and DELCUNEG (cubed absolute value of the difference
      between measure cholesterol and the value of 190 mg/dl when cholesterolemia was,
      respectively, over and under 190 mg). The first estimation of cholesterolemia was
      taken upon admission to the ICU. The APACHE II score was computed from teh worst
      values obtained during the first 24h of the ICU stay, including the pre-operative
      period for patients transferred from the operating theatre. Mortality (24.4%)
      over the whole time of hospitalization has been considered. A stepwise linear
      logistic regression on APACHE II, DELCUPOS, DELCUNEG, and on interactions among
      these three factors has been carried out. A U-shaped relationship between
      cholesterolemia and morality was demonstrated. The significance of DELCUPOS (p =
      0.0021) and DELCUNEG (p = 0.0002), considered together with the APACHE II score,
      has demonstrated an additive information content with respect to the APACHE score
      for the prediction of mortality. CONCLUSION: Both hyper- and hypocholesterolemia
      have a highly significant relationship to mortality. Cholesterolemia improves the
      prognostic power of the APACHE II score. This result could be used to create a
      more powerful prognostic index.

PMID- 8880249
TI  - Different effects of early endotoxaemia on hepatic and small intestinal
      oxygenation in pigs.
AB  - OBJECTIVE: Study on simultaneous O2 supply/uptake relationships in liver and gut
      during endotoxaemia, to determine whether signs of dysoxia develop uniformly in
      the splanchnic region. DESIGN: Animal study to assess the early effects of
      endotoxaemia on oxygenation of both liver and small intestine. INTERVENTIONS:
      Eight anaesthetized pigs received a continuous portal venous infusion of
      lipopolysaccharide (0.5 microgram.kg-1.h-1) for 6 h. Systemic, pulmonary and
      splanchnic haemodynamics as well as systemic and splanchnic O2 supply/uptake
      relationships were determined. RESULTS: There was a multiphasic haemodynamic
      response pattern characterized by an early (within the 1st h) and a subsequent
      more prolonged phase (between the 2nd and 6th h) of decreases and recovery of
      hepatic arterial, portal venous and superior mesenteric arterial blood flows
      (electromagnetic flow probes) and splanchnic O2 deliveries. Unrelated to
      perfusion pressure and O2 delivery, there were early and sustained decreases in
      ileal mucosal surface partial pressure of oxygen (PO2) (multiwire PO2 electrode)
      and pH (tonometry). This was not reflected by ileal serosal surface PO2, O2
      uptake and arteriomesenteric venous pH and partial pressure of carbon dioxide
      (PCO2) gradients. There was little evidence of concomitant hepatic dysoxia as
      evaluated by surface PO2. CONCLUSIONS: The study demonstrates early and sustained
      regional (mucosa) intestinal hypoxia with little evidence of simultaneous hepatic
      dysoxia during initial endotoxaemia.

PMID- 8880250
TI  - Influence of continuous positive airway pressure on EMG activities of the
      cricothyroid and posterior cricoarytenoid muscles of the canine larynx.
AB  - OBJECTIVES: We investigated the effect of different levels of continuous positive
      airway pressure (CPAP) on the cricothyroid (CT; a tensor muscle of the vocal
      folds) and posterior cricoarytenoid (PCA; sole abductor muscle of the vocal
      folds) muscles in dogs. DESIGN: Prospective, controlled animal study. SUBJECTS:
      Nine mongrel dogs of both sexes. SETTING: University research laboratory.
      INTERVENTIONS: After insertion of a cuffed tracheotomy tube low in the neck the
      compound EMG responses of the CT and PCA muscles during spontaneous respiration
      were measured simultaneously under different levels (2, 4, 6, and 8 cmH2O) of
      positive end-expiratory pressure (PEEP). MEASUREMENTS AND RESULTS: The CT showed
      a progressive increase in phasic expiratory EMG activity with the application of
      graded levels of PEEP. Application of PEEP over 4 cmH2O produced significant
      increases in the phasic CT activity (P < 0.05). In contrast to the CT, the PCA
      failed to increase phasic inspiratory EMG activity statistically until a 8 cmH2O
      of PEEP was applied (P < 0.05). The phasic expiratory CT and inspiratory PCA
      activities were 297.9 +/- 77.6 and 124.5 +/- 22.9, respectively, at the
      application of 6 cmH2O of PEEP (percentage of control, mean +/- SD). CONCLUSION:
      This study confirms the difference in sensitivity between adductor and abductor
      laryngeal muscles, demonstrating that the intrinsic laryngeal muscles do not all
      behave similarly after the application of CPAP.

PMID- 8880252
TI  - Haemodynamic and respiratory conditions during alternating and synchronous
      ventilation of both lungs.
AB  - OBJECTIVE: We tested the hypothesis that mean thoracic expansion (and mean lung
      volume) is lower during alternating ventilation (AV), i.e. ventilation of both
      lungs with a phase shift of half a ventilatory cycle, compared to synchronous
      ventilation (SV) of both lungs. As a consequence, intrathoracic pressure will be
      lower, causing lower, central venous pressure and higher cardiac output. DESIGN:
      In eight anaesthetized and paralysed piglets, differential ventilation was
      established by fixation of an endobronchial tube in the left main bronchus. SV
      and AV were sequentially applied for four and three periods, respectively, of 10
      minutes each. Minute ventilation was the same during AV and SV and adapted to
      normocapnia. Two series of observations were performed: series 1 with intact
      thorax and monitoring of oesophageal pressure; series 2 after perforation of the
      sternum, airtight closure of the thorax and monitoring of pericardial pressure.
      RESULTS: In both series, mean lung volume was 16 +/- 4% lower and central venous,
      oesophageal (series 1) and pericardial pressures (series 2) were 0.5-0.7 mmHg
      lower during AV compared to SV (all p < 0.001). In series 1, aortic pressure was
      5 mmHg and cardiac output 8% higher (both p < 0.001). In series 2, cardiac output
      was 5% higher during AV (p < 0.001), but aortic pressure did not change (p =
      0.07). CONCLUSION: Our data verified the hypothesis. The lower oesophageal
      (series 1), pericardial (series 2) and central venous pressures during AV
      compared to SV could be explained by the smaller thoracic expansion due to the
      lower mean lung volume, which was attributed to compression of the opposite lung
      by the, expansion of the inflated lung.

PMID- 8880251
TI  - Fulminant malignant hyperthermia associated with ketoacidotic diabetic coma.
AB  - Malignant hyperthermia (MH) in humans is usually triggered by volatile
      anaesthetics and depolarizing muscle relaxants. However, other factors or drugs
      (e.g. cresol) are thought to induce MH. We report a case of fulminant MH
      associated with a ketoacidotic diabetic coma. After therapy for diabetic coma
      with insulin (containing the preservative cresol) and electrolyte solutions was
      started, the patient complained of increasing myalgia, developed a high fever and
      respiratory and metabolic acidosis and lost consciousness. MH was treated
      immediately with dantrolene; the patient recovered within 14 days. Five months
      later the patient was diagnosed as MH-susceptible by the in vitro caffeine and
      halothane contracture test. This case supports the assessment that MH and
      diabetes are associated diseases and that cresol could possibly trigger MH.
      Furthermore, therapy with dantrolene has been demonstrated to be beneficial in
      the treatment of MH associated with diabetic coma.

PMID- 8880253
TI  - Continuous intra-arterial blood gas monitoring.
AB  - OBJECTIVE: To review the technology, clinical trials and current status of
      continuous blood gas monitoring in intensive care. DESIGN: The review describes
      the history, technology, various clinical trials on continuous blood gas
      monitoring and discusses the various factors which might affect their performance
      characteristics and outlines their potential role in intensive care and during
      anaesthesia. CONCLUSIONS: Over the past 10 years a number of continuous intra
      arterial blood gas monitoring systems have been developed. The performance
      characteristics of these systems are comparable. Their levels of accuracy as
      measured in bench tonometry are not consistently achieved in clinical trials. The
      potential usefulness of these monitors in various clinical situations has been
      described in case studies. Controlled studies demonstrating an improvement in
      outcome with the use of these monitors have not been published.

PMID- 8880255
TI  - True knot in a Swan-Ganz catheter on a central venous catheter: a simple trick
      for percutaneous removal.

PMID- 8880254
TI  - Diagnosis of intravascular device related sepsis by a continuous monitoring blood
      culture system.

PMID- 8880256
TI  - Liver transplantation in a case of fulminant liver failure after exertion.

PMID- 8880257
TI  - Fatal Aspergillus pericarditis in acquired immunodeficiency syndrome.

PMID- 8880258
TI  - Biocompatible dialysis membrane in acute renal failure: the best choice. French
      Study Group on Acute Renal Failure.

PMID- 8880259
TI  - Hypertriglyceridaemia associated with propofol sedation in critically ill
      patients.

PMID- 8880260
TI  - Respiratory distress syndrome and septic shock due to varicella in an HIV
      infected adult.

PMID- 8880262
TI  - Percutaneous dilatational tracheostomy.

PMID- 8880261
TI  - Reliability of brain death diagnostics.

PMID- 8880263
TI  - Care for records for care.
AB  - In this contribution the topic of this special issue is introduced: electronic
      patient records (EPRs). The characteristics of EPRs are presented. A number of
      problems that have to be solved before EPRs can be used on a large scale is
      discussed.

PMID- 8880264
TI  - The computer-based record: patient moving from concept toward reality.
AB  - In 1991 the Institute of Medicine issued a report on improving patient records
      which has proven to be a landmark for the many individuals and institutions
      involved in the development of computer-based patient records (CPRs). The report
      called Computer-based Patient Records: An Essential Technology for Health Care,
      recommended that CPRs become the primary form for patient records, and urged
      widespread implementation of CPRs within a decade. It also provides a framework
      for reviewing the current status of CPRs. In reviewing progress that has been
      made toward CPRs since the Institute of Medicine (IOM) report was released, it is
      useful to look beyond the IOM report's major focus on efforts in the USA and
      include international activities related to CPR development and implementation.
      Looking forward, CPR efforts are likely to be expedited through greater
      collaboration.

PMID- 8880265
TI  - A multi-strategy approach for medical records of specialists.
AB  - Despite a number of well recognized shortcomings of paper medical records, the
      use of a Computer Patient Record (CPR) is not widespread among specialists. The
      complexity of specialized care combined with the diversity of their domains of
      expertise, make it a challenge to design a CPR that satisfies the needs of a
      specialist. Ideally, CPRs are tailored to the specific tasks of each user, and
      yet general enough to permit exchange and sharing of information. The basic
      philosophy behind our CPR is a 'mother' record, which is extended with
      specialized sub-records. Two different types of subrecords are discussed: one to
      accommodate standardized data entry in the context of a specialty or research
      protocol, and another for structured recording of accidental findings outside
      one's own domain of expertise. The CPR supports the entry of free text and does
      not impose structured data entry on the physician, but stimulates him to do so by
      confronting him with the benefits of a structured CPR.

PMID- 8880266
TI  - How to approach the structuring of the medical record? Towards a model for
      flexible access to free text medical data.
AB  - The development and dissemination of Electronic Medical Records (EMR) is impeded
      because of several reasons. One of the reasons is considered the 'unruliness' of
      narrative data. In this article it is illustrated how the medical record can be
      structured to make it accessible from different perspectives, without the need to
      change the free text format of the narratives. The organising principles behind
      three existing medical record structures are analysed: the source-oriented,
      problem-oriented and time-oriented medical record. These principles are combined
      in a model of the medical record with four different views on medical data: a
      typological view, a time view, a problem view, and a process view. A data model
      is presented in which each of these views can be defined. In the discussion some
      examples are given of EMRs in which some of these views have been applied on
      coded data.

PMID- 8880267
TI  - The core of computer based patient records in family practice: episodes of care
      classified with ICPC.
AB  - A central element in the definition of primary care is that primary care
      clinicians address the large majority of personal health care needs of their
      patients. As a consequence, they should document data on these health care needs
      reliably and continuously. To establish whether this occurs, the episode of care
      is the most appropriate unit of assessment: a health problem from its first
      encounter with a health care provider until the completion of the last encounter
      for it. An episode of care is distinguished from episodes of disease and of
      illness. The episode of care as an epidemiological concept for the calculation of
      rates has evolved into a central element of a computer based record. Episode
      oriented data classified with the International Classification of Primary Care
      (ICPC), and specified with ICD-10 as a nomenclature are especially suitable as
      the core of a generic patient record in family practice. ICPC has been available
      to the family medicine community for well over a decade as the main ordering
      principle of its domain. The basic structure of an encounter (within the string
      of encounters which together form an episode of care) distinguishes reasons for
      encounter, diagnoses and diagnostic and therapeutic interventions. In this
      article, a more refined structure of encounters is proposed for a more precise
      documentation of episodes of care in a computer based patient record. The
      conversion structure between ICPC and ICD-10 allows both a high level of
      specificity in the patient's problem list and optimal communication with
      specialists who contribute to the episodes of care for which the documentation is
      the primary care provider's responsibility.

PMID- 8880268
TI  - Unlocking patients' records in general practice for research, medical education
      and quality assurance: the Registration Network Family Practices.
AB  - General practitioners (GPs) possess a wealth of information on the health of
      their patients. Hence, they are in a unique position to gather information for
      research, education or management. The chief goal of the Registration Network
      Family Practices is to establish a computerized database containing certain
      patient characteristics and all relevant health problems excluding minor,
      temporary illnesses. The database can be seen as a dynamic population sampling
      frame of chronic and/or severe morbidity, also including risk factors and
      psychosocial problems. The best way to make use of the Registration Network
      Family Practices is by researchers identifying and sampling patients with
      particular health problems. The database contained patient characteristics and
      problemlists of 61,887 persons, on September 1, 1995. At that time 214,389 health
      problems had been entered in the database. The database is increasingly being
      used as a source of information for studies by researchers and students.
      Researchers find the database a useful tool, but they have to keep in mind that
      data on the process of care are not directly available. Furthermore, there is a
      limit to the number of studies which can be performed in the network practices,
      due to time limitations and the burden on the doctors and patients.

PMID- 8880269
TI  - The proactive medical record.
AB  - In this paper the results are presented from recent developments to increase the
      role of the HISCOM integrated hospital information system to support direct
      patient care. This process has resulted in an operational Electronic Obstetric
      Record System (EVS) and the introduction of a generic system (MDS) to document
      the medical care process starting in the outpatient clinics. These systems are
      based on a model of the clinical care process, agreed upon by clinicians. The EVS
      replaces the conventional paper record and was accepted mainly by the way the EVS
      follows and supports the care process. The main contribution is the completeness,
      the availability, and the support of the care related processes like scheduling
      next appointments and examinations, the reporting and the automatic creation of
      letters. The MDS approach addresses the issue of providing kernel information by
      episode about the care process to clinicians and managers. The MDS is based on
      the episode concept, which is not restricted to the outpatient departments, but
      can also be applied hospital wide, and even across the boundaries of the
      hospital. In this paper the categorisation of 'a proactive medical record' will
      be introduced, and the potential benefits of an integrated approach to the
      electronic medical record (EMR) will be addressed.

PMID- 8880270
TI  - Computerized approach to active and objective quality control of patient care.
AB  - The paper describes a quality control program based on the principles of clinical
      methodology and indicators defined by physicians and hospital administrators
      according to general as well as local needs. The program is supported by a
      knowledge-based system which can be used in two ways: with on-line helps and
      hints to ensure effective and efficient medical decisions on a simulated patient
      for training purposes; and without facilities supporting the user to be used on
      an on-line setting for performance evaluation. The quality control program
      includes the evaluation of effectiveness and efficiency of patient care with
      respect to the overall process, single hypotheses and individual decisions: the
      evaluation regards the number and reliability of activated hypotheses, costs,
      time spent, number and appropriateness of investigations. The overall process is
      recursive, in that the results of each cycle are used by physicians to define new
      goals and indicants for the next cycle; quality control is active because
      physicians under evaluation are directly involved in the definition of goals and
      indicants and in the evaluation of results; evaluation is objective because
      indicants are predefined, and evaluation criteria are transparent.

PMID- 8880271
TI  - Information technology in diabetes care 'Diabeta': 23 years of development and
      use of a computer-based record for diabetes care.
AB  - In this article we have stressed that a diabetes care information system should
      be useful to, usable and actually used by carers at the point of patient contact.
      Information resulting from such encounters should, at no extra cost, furnish the
      needs of communication, audit, research and management. Diabeta is a clinical
      record system for supporting the management of patients with diabetes. It has
      grown 'organically' within an academic clinical unit over a period of 23 years.
      It is used for each and every encounter with the clinicians in our diabetes team
      and as such, contains an immense amount of objective clinical experience. This
      experience can be interrogated very easily by computer-naive clinicians using a
      remarkable interactive program ('Datascan') which contains statistical procedures
      'embedded' in the APL computer code, eliminating the need to 'export' the data
      into a statistical package. The latest PC-based version is incredibly fast and
      this immense amount of clinical experience can be carried around on a notebook PC
      and be available for exploration at any time. This makes 'evidence-based
      medicine' available in a remarkably flexible way since it shares the accumulated
      objective experience of literally 'dozens' of clinicians over a period which now
      extends to 23 years. It adds a completely new dimension to the term 'clinical
      experience' and is unattainable with manual records. It would be naive to assume
      that such systems are easy to design, build or implement, or that the initial
      capital outlay required will be small although costs are falling continuously.
      Medicine is a highly complex activity, the essential basis of which is human
      interaction. Introduction of a technology into this interaction requires
      sensitivity to the wishes and requirements of individuals, and protection of
      their exchanges from third parties. The potential of computers in diabetes care
      is so great that these issues must be addressed through continuing research,
      development, evaluation and funding of new systems. This must be led by the
      medical profession not the computer industry.

PMID- 8880272
TI  - The NUCLEUS integrated electronic patient dossier breakthrough and concepts of an
      open solution.
AB  - This paper addresses the requirements of healthcare providers and hospital
      managers vis-a-vis electronic patient records that can be integrated. It starts
      from some critical failure factors, found with previous attempts to standardise
      the electronic health record. Standardisation appears to be the key issue: the
      subject of standardisation requires delicate positioning. Technology must provide
      us with the means to obtain the standardised foundation for an integrated health
      record concept, which can be completely configured and customised to meet the
      requirements of health professionals and institutions involved. NUCLEUS, project
      A2025 in the AIM programme, has taken on this endeavour, and with good success.
      This paper summarises the benefits of this approach for various categories of
      people interested in using electronic patient records. Moreover, it illustrates
      NUCLEUS' contribution to achieving seamless integration of care. Furthermore,
      this paper explains the conceptual innovations that have been achieved in the
      NUCLEUS project. It consolidates the main concept of Act Management, structuring
      the professional primary process as well as the interprofessional communication.
      These concepts are subsequently expanded to include the key elements of the
      NUCLEUS integrated electronic patient record. Next, the paper reflects on what
      has appeared to be one of the critical success factors of the electronic patient
      record: its configuration and customisation facilities. These facilities make it
      possible to access the patient record at various intuitive aggregation levels and
      to make the integrated patient record 'look like' the individually specialised
      record of the respective healthcare professionals. Finally, the paper addresses
      various topics required to facilitate the successful implementation and operation
      of the NUCLEUS integrated electronic patient record like security, integrity,
      message communication, distribution, heterogeneity and the context of the
      hospital information system.

PMID- 8880273
TI  - The Dutch 'Benefit-II' project: do physicians benefit from using an electronic
      medical dossier?
AB  - In 1992 the Dutch College of General Practitioners (NHG) started a project, which
      lasted until May 1994. The project had three major objectives: establishing as
      exactly as possible what benefits we gain from using an Electronic Medical
      Dossier (EMD) can we find an influence on the quality of care? Which drawbacks or
      problems are there, advising on the optimal use of an EMD; What is the best place
      to record certain data? advising the Working Committee on Informatics (WCIA), of
      Dutch National Association of General Practitioners (LHV) and NHG on the
      directions for the new Reference Model 1995. To obtain these goals panel
      discussions and a questionnaire were used. The project resulted in advice on how
      to use the EMD in the most efficient way. Also we have learned about the use of
      GP-information systems and the perception about this usage by the Dutch GPs.

PMID- 8880274
TI  - Implementation of an electronic patient data management system (PDMS) on an
      intensive care unit (ICU).
AB  - Implementation of a data management system on an Intensive Care Unit (ICU) needs
      a good organisation. The expectations and the specifications of the system should
      be defined and clear before the process is started. Analysis of produced data of
      communication and information pathways on the ICU is necessary. A complete system
      should include data acquisition, data base management and archiving of data. In
      our project, the development of these criteria was performed by participation in
      a national project. Coupling with a hospital information system and the
      possibility of data exchange is mandatory. We were able to implement a paperless
      patient record. Although it takes more time to do the patients administration
      with a Patient Data Management System (PDMS), medical personal seem to be better
      informed. Readable information is easy to access at the bedside of the patient.

PMID- 8880275
TI  - From data to concept management in health care reports. Is there a need for it?

PMID- 8880276
TI  - Linking patient medication data with laboratory information system.
AB  - Dozens of new drugs are taken into clinical use each year. Even if the clinicians
      were able to learn the most important therapeutic effects of the drugs they
      prescribe, they would still be unable to remember all of their minor effects.
      After storing patient related medication data on computerized patient records it
      is possible to build decision support modules which automatically remind of
      possible drug influences on laboratory tests and cause alarms or alerts of drug
      interactions. Medication profiles coded using the Anatomical Therapeutic Chemical
      code (ATC-code) constitutes a valuable part of an Electronic Patient Record
      (EPR). In this paper, we describe the benefits of our system. By building links
      to commercially available drug and laboratory databases we can automatically
      inform clinicians on clinically relevant drug influences on laboratory test
      results.

PMID- 8880277
TI  - Practical success of an electronic patient record system in community care--a
      manifestation of the vision and discussion of the issues.
AB  - This paper analyses the purpose, background, scope, and success to date of
      designing and implementing a comprehensive electronic patient record system for
      community care in the UK, in the context of the increasing policy focus upon
      community care. The project is situated in Plymouth in the UK, a major provider
      of community care. The paper indicates intended benefits of the system for
      patients, professionals, and health care organisations. The rationale behind the
      record content is explained, as is the record structure. Intended uses of the
      records form a further baseline for study, and the paper assesses the key success
      factors to achieving the goal of reliability, quality, and effective use of
      resources.

PMID- 8880278
TI  - Integrated computerized patient records: a two-year Geneva experience.
AB  - The UNIDOC system of computer-based medical records that was developed and made
      operational within the DIOGENE-2 Hospital Information System (HIS), is based upon
      a fully standardized and distributed open systems architecture. It should also be
      emphasized that UNIDOC illustrates a feasible marriage of the two technologies,
      UNIX and MS-DOS, is in many respects successful enough to be recommended as a
      sound general solution to medical office integration into a HIS.

PMID- 8880279
TI  - Applying the object paradigm to a centralized database for a cardiology division.
AB  - In order to master the overwhelming quantity of data produced by the different
      laboratories of our Cardiology Division, we are presently developing a
      centralized database. Our aim is to improve the quality of diagnoses and
      therapies by constituting patient centered medical files integrating logically
      the results of the results of the different examinations and allowing for a rapid
      access to the patient data. The database has to be accessible from an
      heterogeneous set of PC, MacIntoshes and UNIX workstations. It must have an
      ergonomic graphic user interface and generate reports which can be sent to the
      patient physician. It is well known that the requirements for a medical database
      make its conceptual analysis very difficult. As medical knowledge continually
      evolves, the examination protocols change and, therefore, the data sets have to
      be updated. The maintenance of classical databases is usually expensive because
      it requires specialized staff to alter the database structure and to adapt the
      user interface. To allow for flexibility, modularity, code reusability and
      reliability, the object paradigm was applied to a classical relational database.
      Thanks to the combination of both data structure and behavior in single entities,
      it is possible to build generic user interfaces which can be easily tailored to
      the needs of every laboratory of our Cardiology Division.

PMID- 8880280
TI  - An epilepsy information system to support routine and research.
AB  - An epilepsy information system is described that supports routine patient care,
      research, and medical management. The patient's clinical data is ordered in time
      by the date of the patient contact when the data was collected. The clinical data
      is also classified into six categories. An unrestricted text group has text
      subjects in each of these groups as well as in a general free text area. The
      system is integrated with other information subsystems (e.g. patient
      registration, clinical chemistry laboratory, EEG department and pharmacy) as well
      as with the routinely used text processor. Data inquiries for research and
      medical management purposes are programmed in a Structured Query Language (SQL).
      The data needed to answer these queries are taken from the data collected in
      daily routine. The integration of the system is very useful because data only
      have to be entered once and can be used when and where needed. Patient data
      stored in this system is more accessible in general as well as more usable for
      research purposes compared with the patient data previously stored only on paper.

PMID- 8880282
TI  - From medical record to patient record through electronic data interchange (EDI).
AB  - In this contribution the role of Electronic Data Interchange (EDI) for patient
      records is discussed. It is our opinion that unlimited access to patient records
      of different care provides is not a wise thing to do and may even not be
      acceptable legally. The exchange of EDI messages may be a solution in that the
      relevant information is exchanged on a need to know basis under the
      responsibility of the care provider that generated the information. The state of
      the art with respect to the availability of EDI messages in Europe is presented.

PMID- 8880281
TI  - Impact of a protocol processing system (ProtoVIEW) on clinical behaviour of
      residents and treatment.
AB  - A protocol processing system (ProtoVIEW), containing therapeutic trauma
      protocols, was used in the Accident and Emergency (A and E) department for a
      period of 7 months to investigate the impact of automated protocols on firstly,
      medical decision making of physicians and secondly, on quality of treatments
      eventually received by the patients. A randomized controlled trial showed that
      mandatory use of the system led to a more uniform working strategy while fracture
      treatment only seemed to improve in a subgroup of patient for whom residents
      established a correct diagnosis.

PMID- 8880283
TI  - Digital signatures and the electronic health records: providing legal and
      security guarantees.
AB  - This contribution deals with legal issues which arise in the application of
      electronic health records. Especially the issues with regard to ensuring both the
      authenticity of data and their originators are discussed.

PMID- 8880284
TI  - The transitivity of bioequivalence testing: potential for drift.
AB  - During the drug development process bioequivalence studies are required as
      formulations are refined. At the end of this chain of innovator-conducted
      studies, generic manufacturer(s) conduct bioequivalence studies comparing their
      generic(s) to the current marketed formulation. The question we pose is: How
      transitive is bioequivalence? That is, if formulation B is bioequivalent to
      formulation A, and C to B, what can one say about the bioequivalence of C and A?
      We consider 1 (A-B), 2 (A-C), 3 (A-D), and 6 (A-G) bioequivalence steps and
      restrict attention to the current practice of average bioequivalence with an
      (80%, 125%) equivalence criterion. For the cases of no to small differences in
      bioavailability our results suggest that one can be fairly confident of the
      bioequivalence of formulation C to formulation A, and of D to A, but not of G to
      A. The transitivity of bioequivalence decreases with additional steps and with
      increasing power of the individual bioequivalence studies.

PMID- 8880285
TI  - The pharmacokinetics of pranlukast in healthy young and elderly subjects.
AB  - Pranlukast is a novel LTD4 antagonist under development for the treatment of
      asthma. To assess the effect of age, the pharmacokinetics of pranlukast were
      studied in healthy young (9 females, 10 males, mean 30 years) and elderly
      subjects (9 per sex, mean 70.4 years). After an overnight fast volunteers were
      given 300 mg of pranlukast orally, 30 min after a light breakfast. Serial blood
      samples were collected for 24 hs, and the plasma was assayed by HPLC/UV.
      Pranlukast was well tolerated by the volunteers. The resultant mean plasma
      concentration vs. time data were very similar for both age groups. The estimated
      geometric mean AUCO-t and Cmax ratios (95% CI in parentheses) for elderly : young
      were 1.00 (0.71, 1.41) and 0.93 (0.66, 1.33), respectively. Median Tmax occurred
      at 4.5 h in both age groups. There were no significant differences observed in
      the pharmacokinetics of pranlukast between healthy young and elderly subjects. On
      stratifying the young and elderly data with respect to gender, no marked
      differences were observed between male and female subjects in the mean
      pharmacokinetic parameters of pranlukast, and the respective plasma
      concentrations profiles were very similar.

PMID- 8880286
TI  - Effect of alacepril on 24-hour blood pressure in elderly hypertensive patients.
AB  - The effect of administration of an angiotensin-converting enzyme inhibitor,
      alacepril, on 24-hour blood pressure in the elderly hypertensive patients was
      investigated. Thirteen elderly hypertensive patients (mean age 71 +/- 5; 6 male
      and 7 female) participated in the present study. After 2 weeks of control period
      alacepril was administered 25-50 mg/day for 8 weeks. Ambulatory blood pressure
      monitoring with cuff-oscillometric method was performed at the end of both
      control and treatment periods. Alacepril administration for 8 weeks significantly
      decreased 24-hour blood pressure while it had little effect on heart rate.
      Daytime blood pressure was significantly decreased from 154 +/- 10/91 +/- 5 mmHg
      to 145 +/- 8/85 +/- 5 mmHg, while the change in nocturnal blood pressure was not
      significant: from 137 +/- 17/79 +/- 7 mmHg to 130 +/- 15/75 +/- 9 mmHg.
      Hyperbaric area of systolic blood pressure was also significantly decreased (from
      295 +/- 185 mmHg x hour/day to 172 +/- 111 mmHg x hour/day), indicating that
      pressure load to the heart was effectively reduced. Administration of alacepril
      did not cause tachycardia in response to the decrease in blood pressure.
      Acrophase of both blood pressure and heart rate was changed to 11:00 a.m. These
      findings indicate that blockade of the renin-angiotensin system in the elderly
      hypertensive patients decreased blood pressure effectively without causing
      tachycardia or deterioration of diurnal variations of blood pressure. These
      hemodynamic changes produced by alacepril administration are favorable for the
      treatment of the elderly patients with cardiovascular disease.

PMID- 8880287
TI  - The effect of simvastatin on HDL cholesterol in hyperlipidemic patients. Evidence
      of a relationship with the changes in serum triglyceride level.
AB  - The main effect of simvastatin is the decrease of serum cholesterol due to the
      reduction of LDL. A decrease of serum triglycerides and an increase of HDL-C are
      commonly observed during the treatment. The reduction of triglycerides is
      accounted for by the increased catabolism of apo B-containing lipoproteins
      whereas the mechanisms bringing about the increase of HDL-C are still unknown. We
      treated 318 patients with primary hyperlipidemia (227 with phenotype IIa and 91
      with phenotype IIb) with simvastatin 10 mg a day and after 6 weeks we found a
      mean 3% increase in HDL-C. HDL-C increased only in about half of the patients and
      the patients in whom HDL-C increased had baseline higher serum triglycerides and
      had a greater hypotriglyceridemic response than patients in whom HDL-C did not
      increase. Accordingly, HDL-C increased in type IIb patients who experienced a
      greater change in triglycerides than type IIa patients, in whom HDL-C did not
      increase significantly. Apo A-I levels did not change and apo A-I/HDL-C ratio
      significantly decreased. At a daily dose of 40 mg, administered to 51 treatment
      resistant patients, simvastatin produced a marginally greater decrease in serum
      cholesterol and LDL-C, but not in serum triglycerides and HDL-C, than at the
      daily dose of 10 mg. An increase in HDL-C was associated with a reduction in
      serum triglycerides. The decrease in apo A-I/HDL-C ratio suggests that the
      increase in HDL-C after simvastatin must be regarded as an enrichment of the
      cholesterol core of HDL particles. The effect is likely to be due to the decrease
      of the serum concentration of VLDL bringing about a reduction of cholesterol
      transfer from apo A-I to apo B-containing lipoproteins.

PMID- 8880288
TI  - The effect of intravenous metoclopramide on blood pressure in normotensive and
      hypertensive subjects.
AB  - In the present study we evaluated the effect of intravenous metoclopramide on
      blood pressure in normotensive (untrained, football players, runners) and
      hypertensive subjects. There was a decrease in blood pressure only observed in
      untrained female subjects and this was greater in hypertensive subjects. In
      football players and runners the decrease in blood pressure was not statistically
      significant. There was no significant effect on heart rate. The probable
      mechanism of this new pharmacological effect of metoclopramide is unknown,
      however, research is now in progress to define its mechanism of action.

PMID- 8880289
TI  - Pharmacokinetics of theophylline in obesity.
AB  - Pharmacokinetic analysis of theophylline was performed in 16 obese women before
      and after 3-week weight-reducing treatment. Decrease of clearance, increase of
      t1/2, AUC, and MRT were observed. There were no differences between the volume of
      distribution before and after weight-reducing treatment. Our results suggest that
      ideal body weight should be used to calculate a loading dose of theophylline for
      obese patients; weight-reducing treatment may be connected with changes in
      biotransformation and elimination of theophylline more than with its
      distribution.

PMID- 8880290
TI  - Pharmacokinetics of lysine clonixinate in children in postoperative care.
AB  - The pharmacokinetics of 2 doses of intravenous lysine clonixinate (4 and 6 mg x
      kg-1) were studied in 10 children (age 4-10 years) under postoperative care. A
      single dose of the drug was injected in a forearm vein. Blood samples were
      collected at regular intervals for 3 hours. Serum clonixin concentrations
      (expressed as clonixin) were analyzed using a high pressure liquid chromatography
      method. Pharmacokinetic values were estimated by a nonlinear computer program.
      The distribution volume was similar in both groups of children (1.288 +/- 0.829 1
      and 1. 139 +/- 0.667 1, respectively). There were no differences between the
      values of total plasma clearance and the administered doses (0.026 +/- 0.017 ml x
      min-1 and 0.017 +/- 0.008 ml x min-1, t = 1.07, p = 0.76). The elimination half
      life was longer in children who received 6 mg x kg-1 (44.26 +/- 6.34 min vs 38.63
      +/- 10.93 min) but this difference was not statistically significant (t = 0.99, p
      < 0.34). The pharmacokinetic parameters calculated in these children were
      different from those found by other authors in adults and experimental animals.

PMID- 8880291
TI  - Interaction between midazolam and clarithromycin: comparison with azithromycin.
AB  - A comparative pharmacokinetic and pharmacodynamic investigation was carried out
      on the interaction between the hypnotic midazolam and 2 different macrolide-type
      antibiotics, clarithromycin and azithromycin. In an open randomized crossover
      study of 3 phases 12 healthy volunteers received either clarithromycin (250 mg
      twice a day for 5 days), azithromycin (500 mg once a day for 3 days) or no
      pretreatment. On the last day of antibiotic treatment they ingested 15 mg
      midazolam. Plasma samples were collected for midazolam analysis up to 24 h and
      pharmacodynamic performance measured by a series of tests up to 12 h.
      Pretreatment with clarithromycin caused large and statistically significant
      changes in both the pharmacokinetic and pharmacodynamic parameters of midazolam
      compared to control. For example, the AUC was increased from 248.84-888.75 hng/ml
      (factor of 3.57, p < 0.0001) and the mean duration of sleep increased from 135.4
      min to 281.3 min (p < 0.05). No statistically significant effect was found with
      azithromycin in any test. It is concluded that a drug interaction exists between
      midazolam and clarithromycin which could be of clinical importance. No such
      effect is present with azithromycin.

PMID- 8880292
TI  - Randomized placebo-controlled, single blind trial of holy basil leaves in
      patients with noninsulin-dependent diabetes mellitus.
AB  - Experimental studies on albino rats reported that leaf extract of Ocimum sanctum
      and Ocimum album (holy basil) had hypoglycemic effect. To explore further
      evidence we studied the effects of treatment with holy basil leaves on fasting
      and postprandial blood glucose and serum cholesterol levels in humans through
      randomized, placebo-controlled, crossover single blind trial. Results indicated a
      significant decrease in fasting and postprandial blood glucose levels during
      treatment with holy basil leaves compared to during treatment with placebo
      leaves. Fasting blood glucose fell by 21.0 mg/dl, confidence interval of
      difference -31.4 - (-)11.2 (p < 0.001), and postprandial blood glucose fell by
      15.8 mg/dl, confidence interval -27.0 - (-)5.6 (p < 0.02). The lower values of
      glucose represented reductions of 17.6% and 7.3% in the levels of fasting and
      postprandial blood glucose, respectively. Urine glucose levels showed similar
      trend. Mean total cholesterol levels showed mild reduction during basil treatment
      period. The findings from this study suggest that basil leaves may be prescribed
      as adjunct to dietary therapy and drug treatment in mild to moderate NIDDM.

PMID- 8880293
TI  - The founding of the EURO-DURG, the European Drug Utilization Research Group.
AB  - About 240 participants from 35 countries met from June 27-30, 1996 at Lake
      Balaton, Hungary, for the inaugural meeting and also the first specialist
      congress of Euro-DURG. The large number of participants, engaged discussions with
      around 30 lectures, workshops, and extensive poster exhibitions demonstrate not
      only the level of research but also the great interest in cooperation and
      exchange of experiences. EURO-DURG is an umbrella organization for the national
      DUR-groups and is independent of industry. Its objective is the promotion of
      research into drug usage and pharmacoepidemiology as a means for employing
      rational drug therapy. This issue shall be strengthened through international
      cooperation. Methodological questions of research into drug usage, and
      investigations into approaches, and basic conditions for optimizing drug usage
      were the focal points of the meeting.

PMID- 8880294
TI  - Microorganisms in honey.
AB  - Knowledge of the moisture and temperature conditions influencing growth of
      microorganisms in honey has long been used to control the spoilage of honey.
      However, the need for additional microbiological data on honey will increase as
      new technologies for, and uses of honey develop. Microorganisms in honey may
      influence quality or safety. Due to the natural properties of honey and control
      measures in the honey industry, honey is a product with minimal types and levels
      of microbes. Microbes of concern in post-harvest handling are those that are
      commonly found in honey (i.e., yeasts and spore-forming bacteria), those that
      indicate the sanitary or commercial quality of honey (i.e., coliforms and
      yeasts), and those that under certain conditions could cause human illness.
      Primary sources of microbial contamination are likely to include pollen, the
      digestive tracts of honey bees, dust, air, earth and nectar, sources which are
      very difficult to control. The same secondary (after-harvest) sources that
      influence any food product are also sources of contamination for honey. These
      include air, food handlers, cross-contamination, equipment and buildings.
      Secondary sources of contamination are controlled by good manufacturing
      practices. The microbes of concern in honey are primarily yeasts and spore
      forming bacteria. Total plate counts from honey samples can vary from zero to
      tens of thousands per gram for no apparent reason. Most samples of honey contain
      detectable levels of yeasts. Although yeast counts in many honey samples are
      below 100 colony forming units per gram (cfu/g), yeasts can grow in honey to very
      high numbers. Standard industry practices control yeast growth. Bacterial spores,
      particularly those in the Bacillus genus, are regularly found in honey. The
      spores of C. botulinum are found in a fraction of the honey samples tested
      normally at low levels. No vegetative forms of disease-causing bacterial species
      have been found in honey. Bacteria do not replicate in honey and as such high
      numbers of vegetative bacteria could indicate recent contamination from a
      secondary source. Certain vegetative microbes can survive in honey, at cool
      temperatures, for several years. However, honey has anti-microbial properties
      that discourage the growth or persistence of many microorganisms. Typically,
      honey can be expected to contain low numbers and a limited variety of microbes. A
      routine microbiological examination of honey might include several different
      assays. A standard plate count provides general information. Specialized tests,
      such as a count of yeasts and an assay for bacterial spore-formers, may also be
      useful. An indicator of sanitary quality as provided by coliform counts might be
      included. Additional tests, to explain unusually high counts or address a certain
      problem, may be needed. The use of honey in products that receive no or limited
      heat treatment may require additional tests. More information on the source and
      control of microbes in honey is needed to answer the concerns currently facing
      the industry.

PMID- 8880295
TI  - Luminescent Salmonella strains as real time reporters of growth and recovery from
      sublethal injury in food.
AB  - LuxA and luxB genes from V. harveyi carried by a Tn-5 containing plasmid were
      introduced into S. enteritidis by either conjugation or electroporation. Lux
      genes were used as a reporter to indicate the effects of heat treatment (50
      degrees C, 55 degrees C and 65 degrees C) and pH (from 1 to 7) on the survival,
      growth and recovery of Salmonella cells. When a luminescent S. enteritidis
      strain, obtained by electroporation, was subjected to a plasmid curing procedure,
      the resulting culture lost the plasmid but remained luminescent. Southern
      hybridization was performed to determine the location of lux genes in S.
      enteritidis cells. The light output from recombinant cultures with different gene
      locations was compared and found to be higher for strains in which the luciferase
      was plasmid-mediated. The luminescent Salmonella culture was inoculated in food
      samples such as homogenized chicken meat, whole liquid eggs and fluid milk and
      development of luminescence with time was monitored. The minimum number of
      Salmonella cells required for positive observation was approximately 1 x 10(2)
      CFU/ml in broth and homogenized meat cultures, 2 x 10(3) CFU/ml in fluid milk and
      7 x 10(3) CFU/ml in whole liquid egg.

PMID- 8880296
TI  - Fluorogenic and chromogenic enzyme substrates in culture media and identification
      tests.
AB  - Rapid detection and identification of microorganisms is extremely important in
      many fields of applied and research microbiology. In general, fluorogenic and
      chromogenic substrates have proved to be a powerful tool, utilizing specific
      enzymatic activities of certain microorganisms, either in parallel with or
      instead of traditional methods. By incorporation of synthetic fluorogenic or
      chromogenic substrates into primary selective media, enumeration and detection
      can be performed directly on the isolation plate. The introduction of many of
      these media and identification tests has led to improved accuracy and faster
      detection of target organisms, often reducing the need for isolation of pure
      cultures and confirmatory tests.

PMID- 8880297
TI  - Characterization of Lactobacillus sake strains associating with production of
      ropy slime by randomly amplified polymorphic DNA (RAPD) and pulsed-field gel
      electrophoresis (PFGE) patterns.
AB  - Randomly amplified polymorphic DNA (RAPD) patterns and pulsed-field gel
      electrophoresis (PFGE) patterns were used for the characterization of ropy slime
      producing Lactobacillus sake strains. The two most revealing commercially
      available primers (OPJ 12 and OPJ 16, Operon Inc. Alameda, USA) and two rare
      cutting enzymes (AvrII and SmaI) were chosen from a pretested lot for the typing
      of 69 ropy slime-producing strains, 7 non-ropy isolates and 4 non-ropy reference
      strains. Both RAPD and PFGE patterns confirmed the group division established in
      previous studies and provided new information concerning ropy slime-producing
      strains. PFGE patterns were found to have the greatest discriminatory power,
      revealing the genetic variation of the main group of ropy slime-producing L. sake
      strains and distinguishing all non-ropy strains from slime-producers.

PMID- 8880298
TI  - Predictive model of the effect of temperature, pH and sodium chloride on growth
      from spores of non-proteolytic Clostridium botulinum.
AB  - Non-proteolytic strains of Clostridium botulinum are capable of growth at chill
      temperatures and thus pose a potential hazard in minimally-processed chilled
      foods. The combined effect of pH (5.0-7.3), NaCl concentration (0.1-5.0%) and
      temperature (4-30 degrees C) on growth of non-proteolytic C. botulinum in
      laboratory media was studied. Growth curves at various combinations of pH, NaCl
      concentration and temperature were fitted by the Gompertz and Baranyi models, and
      parameters derived from the curve-fit were modelled. Predictions of growth from
      the models were compared with data in the literature and this showed them to be
      suitable for use with fish, meat and poultry products. This model should
      contribute to ensuring the safety of minimally-processed foods with respect to
      non-proteolytic C. botulinum.

PMID- 8880299
TI  - Lactic acid fermentation of cassava dough into agbelima.
AB  - The souring of cassava dough during fermentation into the fermented cassava meal,
      agbelima, was investigated. Four different types of traditional inocula were used
      to ferment the dough and increases in titrable acidity expressed as lactic acid
      from 0.31-0.38 to 0.78-0.91% (w/w) confirmed the fermentation to be a process of
      acidification. The microflora of all inocula and fermenting dough contained high
      counts of lactic acid bacteria, 10(8)-10(9) cfu/g in all inocula and 10(7)-10(8),
      10(8)-10(9) and 10(9) cfu/g at 0, 24 and 48 h in all fermentations. Lactobacillus
      plantarum was the dominant species of lactic acid bacteria during all types of
      fermentation accounting for 51% of 171 representative isolates taken from various
      stages of fermentation. Other major lactic acid bacteria found were Lactobacillus
      brevis, 16%, Leuconostoc mesenteroides, 15% and some cocci including
      Streptococcus spp. whose numbers decreased with fermentation time. The lactic
      acid bacteria were responsible for the souring of agbelima through the production
      of lactic acid. All L. plantarum, L. brevis and L. mesenteroides isolates
      examined demonstrated linamarase as well as other enzymatic activities but did
      not possess tissue degrading enzymes like cellulase, pectin esterase and
      polygalacturonase. The aroma profile of agbelima did not vary with the type of
      inoculum used and in all samples the build-up of aroma compounds were dominated
      by a non-identified low molecular weight alcohol, 1-propanol, isoamyl alcohol,
      ethyl acetate, 3-methyl-1-butanol and acetoin. Substantial reductions occurred in
      the levels of cyanogenic compounds present in cassava during fermentation into
      agbelima and detoxification was enhanced by the use of inoculum.

PMID- 8880300
TI  - Induction of IFN-gamma and IL-1 alpha production in macrophages stimulated with
      phosphopolysaccharide produced by Lactococcus lactis ssp. cremoris.
AB  - The induction of interferon (IFN) and interleukin-1 (IL-1) production in murine
      macrophages by a phosphopolysaccharide, produced by a dairy lactic acid bacteria,
      Lactococcus lactis ssp. cremoris, was investigated. When the
      phosphopolysaccharide was added into macrophage cultures at concentrations from 1
      to 200 micrograms/ml, substantial IFN titers (6.2-79.2 IU/ml) were detected.
      Using the reverse transcription-polymerase chain reaction (RT-PCR), the
      expression of mRNA encoding IFN-gamma was verified in spleen macrophage cultures.
      Macrophages stimulated with the phosphopolysaccharide also produced IL-1 alpha at
      a concentration of 50 micrograms/ml. This study showed for the first time that
      phosphopolysaccharide derived from a dairy lactic acid bacterium can induce IFN
      gamma and IL-1 alpha production in macrophages. These findings strongly suggest
      that the phosphopolysaccharide is a type of 'biological response modifier' and
      the fermented dairy foods containing Lactococcus lactis ssp. cremoris can be
      designated as a physiologically functional food.

PMID- 8880301
TI  - Changes in microbial populations on fresh cut spinach.
AB  - The microbial populations found on fresh-cut spinach leaves that were stored in
      gas permeable bags at 10 degrees C for 12 days were examined and identified. The
      microorganisms consisted of mesophilic aerobic bacteria, psychrotrophic bacteria,
      Pseudomonadaceae, Enterobacteriaceae, Micrococcaceae, lactic acid bacteria and
      yeasts. Populations of mesophiles, psychrotrophs, Pseudomonadaceae and
      Enterobacteriaceae increased sharply during the storage period. The initial
      populations were 10(7), 10(6), 10(6) and 10(4) CFU.g-1 respectively. Populations
      reached 10(10) for the mesophiles, psychrotrophs and Pseudomonadaceae and 10(7)
      CFU.g-1 for Enterobacteriaceae after 12 days of storage. Micrococcaceae, lactic
      acid bacteria and yeasts remained constant (10(3)-10(4) CFU.g-1. The majority of
      the bacterial isolates were identified as Pseudomonas fluorescens, Aeromonas
      caviae and Staphylococcus xylosus. The yeasts, which were most frequently
      isolated, were classified in the genus Cryptococcus. No pathogens such as
      Listeria monocytogenes and Salmonella were detected. Observations with low
      temperature scanning electron microscopy (LTSEM) indicated that the
      microorganisms were not present on the surface of healthy unbroken leaves.
      Alternatively, they were found in areas where the cuticle was broken and could be
      seen infecting the internal palisade parenchyma.

PMID- 8880302
TI  - Incidence and toxigenicity of Aeromonas hydrophila in seafood.
AB  - Three selective media, Oxoid Aeromonas agar (OA), blood ampicillin agar (BA) and
      starch ampicillin agar (SA) were used to evaluate the presence of Aeromonas
      hydrophila in 66 samples of oyster, shrimp, fish and surimi products. Oyster had
      the highest incidence, with 50% positive, whilst no A. hydrophila was found in
      the surimi. Of the three selective media, BA displayed the highest recovery rate
      of A. hydrophila from seafood. Forty-eight isolates from this survey were tested
      for their capability to produce hemolysin and cytotoxin. Hemolysin was produced
      by 79.2% of the isolates and cytotoxin was produced by 91.7% of the isolates in
      brain heart infusion broth. One of the toxin-producing isolates from oyster,
      strain 8-169, was further tested for growth and toxin production in oyster,
      shrimp and fish at various temperatures. This particular isolate grew best and
      had highest toxin production in oyster. Hemolysin and cytotoxin were produced
      earlier at 28 degrees C than at 37 degrees C, and titers of hemolysin were also
      higher at 28 degrees C. At 5 degrees C, it was able to grow and produce hemolysin
      in oyster.

PMID- 8880303
TI  - Listeriolysin O production and pathogenicity of non-growing Listeria
      monocytogenes stored at refrigeration temperature.
AB  - Three haemolytic, pathogenic strains of Listeria monocytogenes (a reference
      strain NCTC 7973, a food-derived strain L70 and a human strain L94) and a control
      strain of Listeria innocua L27 were held in phosphate-buffered saline (PBS) of pH
      7.0 or 5.5 at 4 degrees C for 4 weeks. The number of viable cells did not change
      significantly during this storage (the cells were non-growing). Titers of
      Listeria listeriolysin O (LLO) activity against washed human erythrocytes and the
      pathogenicity of non-growing bacterial cells for 14-day-old chick embryos were
      determined before storage and after 1, 2, 3 and 4 weeks of storage. Prolonged
      storage at 4 degrees C affected both LLO production and pathogenicity of the non
      growing cells, but effects were strain- and pH-dependent. At pH 7.0, all three L.
      monocytogenes strains had lost LLO activity after 2 weeks of storage. At pH 5.5,
      the reference and the food strains lost LLO activity 1 week later than when
      stored at neutral pH, and the human strain maintained LLO activity throughout the
      4-week period. Pathogenicity of the reference strain stored at pH 7.0 and 5.5 and
      that of the food strain stored at pH 7.0 decreased during storage at 4 degrees C.
      However, the human strain stored at pH 7.0 and 5.5, and the food strain stored at
      pH 5.5, maintained their pathogenicity throughout the 4-week period. In all
      cases, non-growing L. monocytogenes cells that had ceased LLO production and/or
      had a reduced pathogenicity, recovered these characteristics after growth in
      media at 37 degrees C. This study indicates that prolonged storage of chilled
      foods in which L. monocytogenes is present, but not growing may have the
      desirable result that the L. monocytogenes has a reduced ability to cause illness
      in humans. As well, pathogenicity testing involving growth of L. monocytogenes in
      laboratory media may not reflect the actual pathogenicity of the organism in the
      food as eaten.

PMID- 8880304
TI  - Evaluation of serotyping, biotyping, plasmid banding pattern analysis, and HEp-2
      vacuolation factor assay in the epidemiological investigation of Bacillus cereus
      emetic-syndrome food poisoning.
AB  - To assess the value of the plasmid banding patterns, the vacuolation factor (VF)
      assay, biotyping, and serological typing as epidemiological markers for strains
      of Bacillus cereus causing emetic-syndrome illness, 43 isolates from five
      outbreaks and an additional 76 strains isolated in food-poisoning outbreaks
      caused by other enteric pathogens were examined by these techniques, and the
      results were compared. Thirty-eight (88%) of the 43 outbreak strains produced
      vacuolation responses in HEp-2 cells and were all starch-hydrolysis negative. The
      other 76 strains associated with outbreaks caused by other food-poisoning
      bacteria gave all negative VF production results except four strains, and 56
      (74%) of these strains produced positive reactions in starch hydrolysis tests.
      Starch hydrolysis emerged as a convenient screen for VF production, because no
      starch hydrolysis-positive strains produced VF. With the exception of one
      isolate, all 38 VF-positive isolates from emtic-syndrome outbreaks were serotype
      H.1. Isolates from four of the five outbreaks revealed identical plasmid banding
      patterns in each outbreak, whereas only three of eight serotype H.1 strains from
      the fifth outbreak exhibited indistinguishable plasmid banding patterns. These
      results suggest that the plasmid banding pattern analysis may be of value in
      discriminating between isolates of the same serotype, and establishing if an
      outbreak arises from a common food source. In conclusion, the vacuolation factor
      assay combined with the plasmid banding patterns proved to be a valuable tool for
      the epidemiological investigation of emetic-syndrome outbreaks caused by B.
      cereus. Moreover, these methods are particularly useful for laboratories that do
      not have ready access to serotyping facilities.

PMID- 8880305
TI  - Pathways of Listeria monocytogenes contamination in the meat processing industry.
AB  - One hundred and thirty-three isolates of Listeria monocytogenes from deboned
      fresh meat, production environment, cold cuts from five meat processing plants
      and from one plant producing cured dried sausages, were characterized using
      multilocus enzyme electrophoresis. On the basis of electrophoretically
      demonstrable allelic variation at 21 enzyme loci, 21 electrophoretic types (ETs)
      were distinguished. Analysis of the genetic relationships among the 21 ETs
      revealed two distinct clusters: Cluster A and Cluster B. With the exception of
      two isolates from one plant, all isolates from deboned fresh meat belonged to
      Cluster B. During processing of cold cuts, however, isolates belonging to Cluster
      A became more frequent, and only one of the 37 isolates from cold cuts belonged
      to Cluster B. In contrast, six of the nine isolates from cured dried sausages had
      ETs in Cluster B. One clone of Cluster A, ET-6 was isolated from cold cuts in
      four of six plants. This is one of the ETs most frequently recovered from
      patients in Norway. Isolates of ET-6 were further characterized using restriction
      fragment length polymorphism (RFLP) analysis of chromosomal DNA. Six distinct
      restriction patterns were distinguished among the 44 ET-6 strains. In one plant,
      four different RFLP patterns could be identified. Two clone variants seemed to
      have colonized different areas in this plant for at least four years. However, in
      each of the other plants, all ET-6 isolates had the same RFLP patterns.

PMID- 8880306
TI  - The major sources of Salmonella enteritidis in Thailand.
AB  - The data of Salmonella serotypes during 1989-1993 from the World Health
      Organisation (WHO) National Salmonella and Shigella Center, Division of Clinical
      Pathology, Department of Medical Science, Ministry of Health, Thailand was
      analysed and found that the prevalence of Salmonella enteritidis had been
      dramatically increased since 1990. The average S. enteritidis isolates from human
      patient samples was 0.70% +/- 0.41% of the total reported Salmonella isolates
      during 1972-1989 and increased to 1.33%, 2.98%, 9.54%, and 16.98% in 1990, 1991,
      1992, and 1993, respectively. The similar trend of S. enteritidis isolates from
      chicken meat samples were also observed. However, the conclusive epidemiological
      relationship between human and chicken S. enteritidis isolates needs to be proved
      by phage typing or other Salmonella typing methods.

PMID- 8880307
TI  - Use of total of Escherichia coli counts to assess the hygienic characteristics of
      a beef carcass dressing process.
AB  - Swab samples were obtained from 3 sites on the surfaces of beef carcasses passing
      through a high speed dressing process, with 24 samples from each site being
      obtained at each of 4 points in the process. The aerobic microflora recovered
      from each swab after incubation at 25 degrees C was enumerated and characterized,
      and numbers of coliforms and Escherichia coli were determined. The data on
      aerobic flora indicated that skinning results in similar contamination of all 3
      sites, that further deposition of bacteria at the brisket site occurs after
      skinning, and that trimming and washing achieve modest decontamination of the
      neck and brisket site, and extensive decontamination of the rump site. Changes in
      flora compositions during processing were too limited to much affect the
      assessment based on the aerobic flora total counts alone. The E. coli data
      indicated that during skinning the rump site was more heavily contaminated with
      faecal organisms than the other sites, that contamination of the brisket site is
      little altered between skinning and carcass splitting, although there is an
      extensive redistribution of E. coli at the neck site and sporadic, limited
      decontamination of the rump site, and that trimming and washing do not
      decontaminate the neck or rump sites, but that the rump site is extensively
      decontaminated by trimming. There was good correlation between E. coli and
      coliform counts, but weak correlation between E. coli and aerobic, 25 degrees C,
      counts. The findings suggest that assessments of beef carcass dressing processes
      for Hazard Analysis: Critical Control Point (HACCP) purposes should be based on
      enumerations of E. coli, or perhaps coliforms, rather than of the aerobic flora,
      to avoid important misunderstandings of the hygienic effects of the various
      operations in a process.

PMID- 8880308
TI  - Survival of Vibrio cholerae O1 on plastic materials.
AB  - Survival of environmental and clinical strains of Vibrio cholerae O1 was studied
      on glass and on two varieties of plastic materials. V. cholerae survived at least
      2 days on glass, but was not recovered from polystyrene spoons after 15-20 min.
      Escherichia coli survived for at least 2 days on both glass slides and plastic
      spoons. Extracts, 10 and 50% (w/v) of ground plastic spoons in isotonic saline
      water, inactivated 10(4) vibrios in less than 2 h. Isotonic saline water rinses
      from polyethylene bags inactivated (0% survival) 15 out of 23 strains of V.
      cholerae in 1 h. A strain of V. cholerae (100-200 CFU/ml) directly suspended in
      25 ml of isotonic saline per bag and maintained at 20 degrees C was progressively
      inactivated. The number of viable cells diminished 95% in 4 h in bags taken from
      non-sterile rolls. In sterile bags the decrease was 44% and 93% after 4 and 24 h,
      respectively. A variability up to 50% was observed in the antibacterial effect
      among the different bags, either sterile or taken from non-sterile rolls. These
      decreases in V. cholerae viability may result in false negative reports if water
      samples are collected and carried out in plastic bags.

PMID- 8880309
TI  - Growth of yeasts in milk and associated changes to milk composition.
AB  - The growth of several yeast species in milk containing added sodium chloride (0
      15%, w/v) at 25 degrees C and 10 degrees C was examined in conjunction with yeast
      metabolism of milk constituents. Depending on conditions, all yeasts grew to
      maximum populations of 10(7)-10(8) cfu/ml. Kluyveromyces marxianus gave strong
      utilisation of lactose and weak metabolism of citrate, protein and fat with the
      production of ethanol, glycerol, lactic acid and propionic acid. As measured by
      the production of free amino acids and free fatty acids, Candida lipolytica and
      Candida catenulata gave strong proteolytic and lipolytic reactions, the
      specificities of which appeared to be influenced by temperature and the presence
      of NaCl. These species also metabolised organic acids. Although giving strong
      growth responses, Debaryomyces hansenii and Saccharomyces cerevisiae did not
      metabolise lactose and gave only very weak lipolytic and proteolytic reactions.
      Citrate was metabolised by D. hansenii but not by S. cerevisiae. Both species
      produced small amounts of ethanol, glycerol and lactic acid.

PMID- 8880310
TI  - Effect of modified atmosphere packaging on the TVB/TMA-producing microflora of
      cod fillets.
AB  - Cod fillets (Gadus morhua) were packed under modified atmospheres, with four
      different gas compositions (60% CO2-10% O2-30% N2, 60% CO2-20% O2-20% N2, 60% CO2
      30% O2-10% N2, 60% CO2-40% O2), and stored at 6 degrees C. Plate counts were
      carried out after 3, 4, 5, 6 and 7 days, to follow the growth of aerobic and
      anaerobic bacteria, lactic acid bacteria, H2S-producing bacteria and
      Enterobacteriaceae. The production of total volatile bases (TVB) and
      trimethylamine (TMA), and the changes in pH of the fillets were measured.
      Modified atmosphere packaging (MAP) had in general an inhibitory effect on the
      growth of the microflora but limited inhibition of the production of TVB and TMA.
      Despite the fact that increased oxygen proportions in the atmosphere contributed
      in a slightly lower production of TMA, all the samples had a TVB and TMA content
      high enough to be considered as spoiled after 4 days' storage at 6 degrees C. A
      total aerobic plate count at 25 degrees C of a 10(6) cfu/g, combined with the
      presence of only a 10(3) cfu/g of H2S-producing bacteria, which are normally
      considered as TMAO-reducing organisms in fish, cannot explain the strong increase
      in TMA. A high cell concentration of more than 10(8) cfu/g of Shewanella
      putrefaciens is required for production of a TMA level normally found in spoiled
      fish. This suggests that there could be another type of bacterium in fish, not
      involved in the spoilage of unpacked fish, which is resistant to 60% CO2, is not
      H2S-producing, and shows a high TMAO-reducing capacity. This bacterium could be
      Photobacterium phosphoreum.

PMID- 8880311
TI  - Model for the survival of Staphylococcus aureus in nongrowth environments.
AB  - A model was developed to estimate the survival times of Staphylococcus aureus in
      nongrowth environments. A four strain mixture of S. aureus was inoculated into
      BHI broth that had a lactate buffer with various combinations of pH (3-7) and
      lactate (0-1%), NaCl (0.5-20%) and NaNO2 (0-200 ppm) and stored at different
      temperatures (4-42 degrees C). At appropriate times the survivors were enumerated
      by sampling and spreading on TSA plates. The survival curves were modeled with
      two forms of a logistic equation and the D values were determined. Polynomial
      regression equations were then calculated to predict the effect of the
      environmental factors on the D values. Survival times were increased with higher
      pH values, lower temperatures, and lower nitrite and lactate concentrations.
      Added salt increased survival times until the salt concentrations exceeded that
      of most foods.

PMID- 8880312
TI  - Typing of Listeria monocytogenes by monocin and phage receptors.
AB  - One hundred strains of Listeria monocytogenes from both sporadic and epidemic
      cases were typed by monocin production combined with phage receptor and reverse
      phage receptor methods. The monocin-phage combination gave 72 types with 100%
      typability and 97% reproducibility. The results were compared to those of
      serotyping, phage typing, ribotyping, multilocus enzyme electrophoresis,
      restriction enzyme analysis and RAPD (random amplification of polymorphic DNA).
      The monocin/phage types were comparable in terms of discrimination with other
      methods for epidemiological investigations. The index of discrimination of using
      the monocin typing and phage receptor/reverse phage receptor method combination
      (0.99) for both the 87 epidemiologically unrelated strains and the
      epidemiologically important serogroup 4 strains was the highest of the seven
      different methods analysed. This combination of methods was simple, highly
      discriminatory and reproducible and can be carried out in a non-specialized
      laboratory. However, like most of the other Listeria typing methods, both the
      method and the indicator test strains need to be standardized.

PMID- 8880313
TI  - Characteristics of a multicomponent first-order model for thermal inactivation of
      microorganisms and enzymes.
AB  - There are several mathematical models that express different types of non-linear
      thermal inactivation of microorganisms and enzymes. Among the models the
      characteristics of a multicomponent first-order model were studied on a
      calculative simulation. For the initial period of inactivation the pattern of the
      model was predominantly affected by the kinetics of the component with the
      highest initial concentration. For longer periods of inactivation the pattern was
      predominantly affected by the kinetics of the component whose rate constant was
      the lowest. It was also found that the observation period affected the apparent
      pattern of the model. The estimation method of parameter values of the model from
      inactivation curves was then studied.

PMID- 8880314
TI  - Multilocus enzyme electrophoretic (MEE) analysis of Australian isolates of
      Salmonella enteritidis.
AB  - Seventy-three Australian isolates of Salmonella Enteritidis (SE) were analysed by
      multilocus enzyme electrophoresis (MEE) using a polyacrylamide gel system.
      Analysis of 11 enzyme loci identified eight electrophoretic types (ETs), with 61
      of the isolates assigned to ET1, and 72 isolates considered to represent a clonal
      lineage. Representative isolates of each of the Australian ETs were then compared
      with isolates from England, Germany and the United States, using a starch gel
      system and 13 enzyme loci. The overseas isolates formed a single ET with
      representatives of the major Australian ET. It is concluded that Australian
      isolates of SE are closely related genetically to those from countries in which
      egg-borne transmission is common.

PMID- 8880316
TI  - Screening of Salmonella in naturally contaminated feeds with rapid methods.
AB  - Five commercially available screening methods, the Oxoid MSRV, Merck SALMOSYST
      RAMBACH AGAR combination, Organon Teknika SALMONELLA-TEKTM, Dynal DYNABEADS ANTI
      SALMONELLA and Foss Electric EIAFOSS, were compared to the conventional culture
      procedure for the detection of Salmonella in naturally contaminated feed samples.
      A total of 217 feed samples from animal as well as from vegetable origin were
      examined. Twenty one samples were found to be positive for Salmonella by all
      methods combined. The conventional culture method detected 17 (81,0%), MSRV 19
      (90,5%), SALMOSYST-RAMBACH 8 (38,1%), SALMONELLA-TEK 19 (90,5%), DYNABEADS ANTI
      SALMONELLA 7 (33,3%) and EIAFOSS 21 (100%) of the 21 total Salmonella
      contaminated samples.

PMID- 8880315
TI  - Microbiological analysis of 'black pudding', a Trinidadian delicacy and health
      risk to consumers.
AB  - The prevalences of Salmonella, Escherichia coli and Staphylococcus aureus in
      black pudding which originated from local vendors and supermarkets in Trinidad
      were determined. The enterotoxigenicity of S. aureus strains and occurrence of
      O157:H7 strains amongst E. coli isolates were also investigated. For the 100
      black puddings each sampled from supermarkets and vendors, the mean total aerobic
      plate count (TAPC) per g was 1.8 x 10(7) +/- 1.5 x 10(7) and 1.5 x 10(8) +/- 2.3
      x 10(8), respectively. E. coli was isolated from 56 (56.0%) black pudding samples
      from supermarkets with a mean count per g of 9.2 x 10(6) +/- 7.9 x 10(6) compared
      to a prevalence of 79% (79 of 100) and mean count per g of 3.2 x 10(7) +/- 4.7 x
      10(7) for samples from local vendors. The difference between prevalences was
      statistically significant (P < or = 0.001; chi 2). Only 1 (2.2%) of 45 strains of
      E. coli from supermarket-purchased pudding tested, was an 0157:H7 strain compared
      to 9 (13.6%) of 66 strains of E. coli from vendor-sold black pudding. The
      difference was not statistically significant (P > or = 0.05; chi 2). Five (5.0%)
      of 100 black pudding samples from supermarkets yielded Salmonella, with S. ohio
      being the predominant serotype. For vendor-sold black pudding however, 11 (11.0%)
      samples were positive for Salmonella with a new serotype, S. unnamed (4,12:d-)
      being responsible for 50% (6 of 12) of isolates from this source. Forty samples
      each of black pudding from supermarkets and vendors were all (100.0%) positive
      for S. aureus with mean counts per g being 3.1 x 10(5) +/- 8.8 x 10(5) and 3.3 x
      10(6) +/- 7.7 x 10(6), respectively. Overall, 27 (33.8%) of 80 strains of S.
      aureus tested were enterotoxigenic producing staphylococcal enterotoxins A(SEA),
      SEB, SEC, SED or a combination. It was concluded that black pudding poses a high
      risk to consumers based on the prevalence, microbial load and toxigenicity of the
      pathogens detected.

PMID- 8880317
TI  - Randomly amplified polymorphic DNA (RAPD) assay for genomic fingerprinting of
      Bacillus cereus isolates.
AB  - Randomly amplified polymorphic DNA (RAPD) assay was used for epidemiological
      subtyping of B. cereus and B. lentus. Within 25 isolates of B. cereus up to 22
      strain types could be determined when five primers were used. RAPD patterns,
      which were found in three B. lentus strains, clearly differed form those of B.
      cereus. The RAPD technique proved to be an effective tool for the
      characterization of B. cereus strains.

PMID- 8880318
TI  - Rapid polymerase chain reaction method for detection of Kanagawa positive Vibrio
      parahaemolyticus in seafoods.
AB  - Detection of Kanagawa positive strains of Vibrio parahaemolyticus by polymerase
      chain reaction (PCR) was tested. Primer pairs for specific amplification of tdh
      gene fragment is described. The assay could detect contamination of seafood
      homogenate when PCR was performed using lysate prepared directly from fish
      homogenates. The sensitivity of the assay could be improved to detect less than
      10 cells of V. parahaemolyticus by performing PCR after 8 h enrichment in
      alkaline peptone water.

PMID- 8880319
TI  - Identification and ribotyping of Staphylococcus xylosus and Staphylococcus
      equorum strains isolated from goat milk and cheese.
AB  - Twenty-five strains of staphylococci isolated from goat milk and cheese were
      identified as belonging to the Staphylococcus xylosus/equorum group using the ID
      32 Staph system (bioMerieux, Marcy-L'Etoile, France). This system, however, was
      not able to discriminate between these two species for 19 of the strains tested.
      Ribotyping was performed on these 25 strains, as well as on three reference
      strains of each of these two species. Hybridization membranes were scanned and
      analyzed using the Taxotron software package (Taxolab, Institut Pasteur, Paris,
      France). A dendrogram representation showed that ribotypes were distributed in
      two clear-cut clusters corresponding to S. equorum (21 strains) and S. xylosus
      (four strains).

PMID- 8880320
TI  - Incidence of Listeria spp. in tropical fish.
AB  - The incidence of Listeria spp. in tropical fish and shellfish was studied. The
      isolation protocol included a pre-enrichment, followed by two selective
      enrichment steps and plating on three selective agars. Listeria monocytogenes
      could be detected in 17.2% of finfish and 12.1% of shellfish. L. innocua was the
      most common species encountered. In 6.9% finfish and 5.6% shellfish, both L.
      monocytogenes and L. innocua were detected. Polymerase chain reaction (PCR)-based
      amplification of internal fragments of the iap gene was found to be useful in
      differentiation of L. monocytogenes from L. innocua.

PMID- 8880321
TI  - Effect of pH of the recovery medium on the apparent heat resistance of three
      strains of Bacillus cereus.
AB  - The influence of pH of the recovery medium, in the range 7.6-5.4, on the apparent
      heat resistance of three strains of Bacillus cereus (ATCC 4342, 7004 and 9818)
      has been investigated. The highest counts of heat-injured spores were obtained at
      pH near neutral, decreasing markedly as pH was reduced, especially with longer
      heating times. When the media were acidified, the apparent D-values tended to
      decrease, although some exceptions related to the strain and the nature of the
      medium were observed. z-Values determined were not affected by the pH of the
      medium.

PMID- 8880322
TI  - The sub-typing of Listeria monocytogenes isolates from food, environments
      surrounding food manufacturing sites, and clinical samples in New Zealand using
      multilocus enzyme electrophoresis.
AB  - Listeria monocytogenes strains isolated from food (cheese, meat and fish),
      environments surrounding food manufacturing sites, and clinical samples from
      throughout New Zealand were analyzed by multilocus enzyme electrophoresis. One
      hundred and twenty four strains were divided into 56 electrophoretic types,
      containing primarily clinical isolates and environmental isolates.

PMID- 8880323
TI  - Detection of Clostridium botulinum in fish and environmental samples using
      polymerase chain reaction.
AB  - A test protocol for the detection and enumeration of Clostridium botulinum in
      fish and sediment samples with specific identification of neurotoxin types A, B,
      E and F was developed. Specific amplification products generated by polymerase
      chain reaction (PCR) formed the basis of identification of the toxin-producing
      organism, whereas quantification of the results was achieved with the most
      probable number (MPN) method. Twenty-six C. botulinum strains studied with PCR
      assays after enrichment in trypticase-peptone-glucose-yeast extract (TPGY) broth
      gave identical results as with the mouse bioassay. The suitability of the
      detection method for food and environmental surveys was assessed by running it on
      32 samples of rainbow trout inoculated with spore loads ranging from 10(2) to
      10(6) C. botulinum type E spores per kg. The organism was detected in all
      samples, and MPN estimates corresponded well to inoculum levels. In order to
      assess possible natural contamination, 16 fish and 16 visceral samples of rainbow
      trout, as well as ten aquatic sediment samples were tested. Of these, eight (80%)
      of the sediment samples were positive, with estimated spore counts of C.
      botulinum type E ranging from 95-2710 per kg sample.

PMID- 8880324
TI  - Prevalence, detection and control of Cryptosporidium parvum in food.
AB  - The role of Cryptosporidium parvum as a foodborne pathogen has not been well
      documented. Epidemiological features of this parasitic protozoon lead to the
      assumption that the incidence of cryptosporidiosis due to contaminated food is
      under-estimated. The high prevalence of C. parvum among dairy herds has increased
      the spread of oocysts in the farm environment, and their potential presence in
      raw milk and other raw foods. In October 1993, the first well-documented
      foodborne outbreak was reported in Maine, USA, and was caused by contaminated
      hand-pressed apple cider. Although various cases of cryptosporidiosis among
      humans have pointed to raw milk and other raw foods as possible sources of
      infection, a conclusive demonstration of foodborne cryptosporidiosis has rarely
      been established. The limited numbers of oocysts in the suspected samples and the
      lack of sensitive detection methods adapted for oocyst detection in food
      contribute to this under-reporting. This review paper discusses various aspects
      of Cryptosporidium spp. and cryptosporidiosis, including the routes of
      transmission, the control of oocysts in food, and the available detection
      methods. The polymerase chain reaction (PCR) combined with DNA probe
      hybridization is a promising detection method. Recent knowledge on the molecular
      biology of the parasite for the development of new PCR assays and their potential
      use in the detection of C. parvum in food are described.

PMID- 8880325
TI  - Production of antifungal substance by Lactococcus lactis subsp. lactis CHD-28.3.
AB  - Six of the 2100 colonies of lactic acid bacteria isolated from 4 month old
      Cheddar cheese and raw buffalo milk showed antifungal activity against
      Aspergillus flavus IARI when tested by the well agar diffusion assay on Potato
      Dextrose Agar containing 0.1% Triton X-100. Out of these, the most promising
      isolate having a broad spectrum of antifungal activity including Aspergillus
      flavus IARI, A. flavus NCIM 555, A. parasiticus NCIM 898 and Fusarium spp. was
      identified as Lactococcus lactis subsp. lactis CHD-28.3. Among the mold cultures
      used as indicator strains, the most sensitive towards antifungal substance
      produced by the test culture was A. flavus IARI. The cell-free supernatant of the
      test culture in Elliker's broth adjusted to pH 6.8 produced an inhibition zone of
      15-19 mm against A. flavus IARI, A. flavus NCIM555 and A. parasiticus NCIM898.
      The isolate when grown at 30 degrees C for 48 h in Elliker's broth showed optimum
      antifungal activity. When the supernatant was neutralized to pH 7.0 or 7.5, there
      was little reduction in activity. However, after enzymatic treatment of
      supernatant with chymotrypsin, trypsin and pronase E, the antifungal activity
      disappeared which indicated the proteinaceous nature of the antifungal substance.

PMID- 8880326
TI  - Campylobacter incidence on a chicken farm and the spread of Campylobacter during
      the slaughter process.
AB  - To get a better understanding of the epidemiology of Campylobacter, a chicken
      farm was studied for 16 weeks with samplings in each flock weekly from input
      until the flock became colonized with Campylobacter or slaughtered. Samples were
      taken from fresh droppings and from drinkers during the rearing period, as well
      as from the environment in empty houses. The spread of Campylobacter during the
      slaughter process was also surveyed. No Campylobacter was found in samples from
      newly-hatched or one-week-old chickens or their drinkers. All flocks but one were
      colonized at two to five weeks of age. All Campylobacter isolates belonged to the
      same sero- and biotype; C. jejuni Penner 2. The spread of Campylobacter in the
      flock was rapid and usually all samples were positive once colonization had been
      proven. C. jejuni was isolated from flies in ante-rooms as well as from air in
      chicken units in houses with positive chicken flocks. Samples were taken at
      slaughter when some of the Campylobacter positive flocks from the farm were
      slaughtered. Campylobacter were isolated from all sampled equipment along the
      processing line, from the chicken transport crates to the chillers, as well as
      from the air.

PMID- 8880327
TI  - Bacterial mutagenicity of terasi and antimutagenicity of Indonesian jasmine tea
      against terasi.
AB  - Terasi, a traditional fermented product of Indonesia was evaluated by Salmonella
      mutagenesis assay. The higher the heating temperature and the longer the heating
      time, the more mutagenicity observed in both terasi and its starter, and the
      highest mutagenic activity was shown by heating each of them at 100 degrees C for
      60 min. Terasi starter has stronger mutagenic properties as compared to terasi.
      Indonesian jasmine tea, which is a yellow tea, was examined for its antimutagenic
      properties against mutagenic terasi. Tea component presented in fraction C (water
      soluble, chloroform and ethyl acetate insoluble fraction) as well as in fraction
      D (water soluble, chloroform, ethyl acetate and n-butanol insoluble fraction)
      were found to suppress the mutagenicities exerted by heated terasi and heated
      terasi starter. Yet, the tea components presented in fraction E (chloroform
      soluble fraction) were found to enhance the mutagenicity of terasi.

PMID- 8880328
TI  - The combined effects of environmental conditions on lipolysis of pork fat by
      lipases of the meat starter culture organisms Staphylococcus xylosus and
      Debaryomyces hansenii.
AB  - The effects of environmental conditions on lipolysis by cell-free extracts from
      the meat starter culture organisms Staphylococcus xylosus and Debaryomyces
      hansenii were studied using pork fat emulsions as model systems. For the
      individual effects of temperature and pH it was found that the optimal conditions
      for the lipolysis by S. xylosus lipase were 37 degrees C and pH 7.0, and 37
      degrees C and pH 6.5 for the lipolysis by D. hansenii lipase. For the combined
      effects of conditions relevant to meat fermentation, i.e. 10-30 degrees C, pH 4.7
      6.0, 2.5-7.5% (w/v) NaCl and incubation times of 2-6 days, the empirical models
      indicated that temperature, pH and incubation time had important effects on total
      lipolysis whereas NaCl concentration had little effect. For both cultures
      lipolysis was strongly inhibited at conditions of meat fermentation compared to
      optimal conditions. For any set of the conditions which were examined the total
      lipolysis caused by D. hansenii lipase was lower than that caused by S. xylosus
      lipase.

PMID- 8880329
TI  - Predictive models of the effect of temperature, pH and acetic and lactic acids on
      the growth of Listeria monocytogenes.
AB  - The combined effect of temperature (1-20 degrees C), pH (4.5-7.2) and acetic acid
      (0-10,000 mg/l; model 1) or lactic acid (0-20,000 mg/l; model 2) on growth of
      Listeria monocytogenes in laboratory media was studied. Growth curves at various
      combinations of temperature, pH and acid concentration were fitted by the model
      of Baranyi and Roberts (1994), and specific growth rates derived from the curve
      fit were modelled. Predictions of growth from the models were compared with data
      in the literature, and this showed the models to be suitable for use in
      predicting growth of L. monocytogenes in a range of foods including meat,
      poultry, fish, egg and milk and dairy products. The two models are compatible,
      i.e. they give similar predictions for cases when no acid is present.

PMID- 8880330
TI  - Growth of Shigella flexneri in foods: comparison of observed and predicted growth
      kinetics parameters.
AB  - Shigella causes foodborne gastrointestinal illness; however, little information
      is available on its ability to grow in foods. Commercially available sterile
      foods (UHT milk, beef broth, chicken broth, vegetable broth, meats, vegetables)
      were inoculated with S. flexneri 5348 and incubated at 12, 15, 19, 28 or 37
      degrees C. Growth curves were fitted from plate count data by the Gompertz
      equation and exponential growth rates, generation times, lag times and maximum
      population densities were derived. The observed kinetics values, expressed as
      T1000 (time, h, required for a 3 log increase in bacterial population), were
      compared with values calculated using published growth models. Observed and
      calculated values compared favorably for growth at 19-37 degrees C. S. flexneri
      grew well in milk at 15-37 degrees C but growth at 12 degrees C was variable. The
      bacteria readily grew in most foods, even at 12 degrees C; but died off in
      carrots at 19 and 28 degrees C. Factors other than those used in the growth model
      may influence bacterial growth in specific foods.

PMID- 8880331
TI  - Polymerase chain reaction for detecting Escherichia coli O157: H7.
AB  - Escherichia coli O157:H7 is known as an important cause of hemorrhagic colitis
      and hemolytic uremic syndrome. Real-time procedures that are sensitive for
      detecting small populations of this bacterium in food are lacking and needed. An
      expression library was constructed by ligation of BamHI-EcoRI DNA fragments of E.
      coli O157:H7 to plasmid vector pUC19 and transformation of recombinant plasmids
      to E. coli JM109. A clone that contained a specific DNA fragment of E. coli
      O157:H7 was identified by colony immunoblot assay using monoclonal antibody MAb
      4E8C12 that uniquely links to E. coli O157:H7 and a few other serotypes of
      verotoxin-producing E. coli. The DNA sequence of the clone consisted of 110 bp of
      5' region of enterohemorrhagic E. coli (EHEC) eae gene and a 688 bp DNA fragment
      adjacent to 5' end of the eae gene, including an unknown function gene encoding
      156 amino acids. A pair of oligonucleotide primers was synthesized based on the
      sequence of the 688 bp fragment. The primers were used in a polymerase chain
      reaction (PCR) to amplify a target DNA of 633 bp. The primers amplified 1 ng of
      DNA from 67 strains of E. coli O157:H7, two strains of E. coli O157:NM, and 7 of
      11 E. coli O55:H7 and O55:NM strains, but not 50 ng of DNA from 34 strains of 29
      other E. coli serotypes and 25 strains of 8 other bacterial species. Annealing
      temperatures from 60 to 63 degrees C could be used for the PCR without loss of
      specificity. The minimum amount of target DNA detected by the PCR was 5 pg. When
      a boiling method and GeneReleaser were used, the PCR was able to detect as few as
      25 and 38 CFU of E. coli O157:H7, respectively, in 3 h.

PMID- 8880332
TI  - Growth of Clostridium perfringens from spore inocula in sous-vide turkey
      products.
AB  - Clostridium perfringens growth from a spore inoculum was investigated in vacuum
      packaged, cook-in-bag ground turkey (pH 6) that included 0.3% (w/w) sodium
      pyrophosphate, and sodium chloride at 0, 1, 2, or 3% (w/w). The packages were
      processed to an internal temperature of 71.1 degrees C, ice chilled and stored at
      various temperatures. The total C. perfringens population was determined by
      plating diluted samples on tryptose-sulfite-cycloserine agar followed by
      anaerobic incubation at 37 degrees C for 48 h. At 28 degrees C, the addition of
      3% salt in turkey was effective in delaying growth for 12 h. At 15 degrees C,
      growth occurred at a relatively slow rate in the presence of 1-2% salt.
      Vegetative cells were not observed even after 28 days of storage in the presence
      of 3% salt. C. perfringens growth was not observed at 4 degrees C regardless of
      salt levels. The D-values ranged from 23.2 min (no salt) to 17.7 min (3% salt).
      Cyclic and static temperature abuse of refrigerated products for 8 h did not lead
      to growth by C. perfringens from a spore inoculum.

PMID- 8880333
TI  - Investigation of an outbreak of human salmonellosis caused by Salmonella enterica
      ssp. enterica serovar Infantis by use of pulsed field gel electrophoresis.
AB  - Analysis of chromosomal DNA restriction patterns produced by pulsed field gel
      electrophoresis (PFGE) was used to investigate an outbreak of human salmonellosis
      caused by Salmonella enterica ssp. enterica serovar Infantis (S. Infantis)
      involving more than 500 registered human cases. The outbreak had been tentatively
      traced back to a single pig slaughterhouse. A total of 135 isolates from various
      sources produced 21 different PFGE patterns with the restriction endonuclease
      XbaI. All human isolates from the outbreak belonged to a single type, the 'EPI
      type', whereas human isolates recovered before and after the outbreak belonged to
      several different types. All isolates investigated from the suspect pig
      slaughterhouse and its supplier pig herds belonged to the EPI-type. Isolates from
      pork from the central meat market in Copenhagen, which received most of the
      carcasses from the suspect slaughterhouse, also belonged to the EPI-type. This
      was furthermore, the case for isolates from beef from the same market, indicating
      that cross-contamination had taken place. All isolates from pork and some, but
      not all, isolates from beef, collected in butchers' shops during the outbreak
      belonged to the EPI-type. The typing results supported that the outbreak was a
      common source outbreak, probably originating from a limited number of supplier
      pig herds supplying animals to a single slaughterhouse.

PMID- 8880334
TI  - Predictive modeling of the growth of Listeria monocytogenes in CO2 environments.
AB  - The effects of pH (5.5, 6.5), temperature (4, 7 and 10 degrees C) and carbon
      dioxide (10, 30, 50, 70 and 90%) on the growth and/or survival of a five strain
      mixture of Listeria monocytogenes were examined in brain heart infusion broth.
      All three variables had a major influence on the growth characteristics of the
      organism. As expected, both the lag time and generation time increased as the CO2
      level increased, and as pH and temperature decreased. Growth over a 30-day period
      was observed at all parameter combinations tested, except at pH 5.5, 4 degrees C
      in the presence of either 50, 70 or 90% carbon dioxide. Two primary models, the
      Gompertz and Baranyi equations, were compared for their ability to describe the
      growth of L. monocytogenes. In general, the Gompertz model predicted both longer
      lag and shorter generation times, compared to the Baranyi model. The Baranyi
      model appeared to fit the overall data better than the Gompertz model. However,
      these differences were often small. Response surface models were developed for
      predicting the effects and interactions of the three independent variables on the
      growth and/or survival of L. monocytogenes in the different modified atmospheres.
      Results demonstrate the importance of strict temperature control for maintaining
      the advantages of food shelf life extension in enriched carbon dioxide
      environments. The information obtained in this study could be used as a guide to
      manufacturers of modified-atmosphere packaged foods, especially when designing
      products in which this organism may be a concern.

PMID- 8880335
TI  - Chemiluminescent enzyme immunoassay for detection of PCR-amplified enterotoxin A
      from Clostridium perfringens.
AB  - A PCR protocol was developed for the rapid and specific detection of Clostridium
      perfringens strains harboring the enterotoxin A gene in artificially contaminated
      ground beef. A biotinylated primer pair was designed for amplification of a 750
      bp fragment of the C. perfringens enterotoxin A gene. A combination of 4 h
      enrichment incubation and nucleic acid extraction, followed by 2 h of PCR
      amplification allowed detection at levels below 10 CFU of freshly grown cells in
      raw and cooked beef samples. PCR amplified products were confirmed by a Southern
      hybridization assay using a digoxigenin-labeled internal probe, and two
      hybridization ELISA protocols (PCR-ELISA) applying a streptavidin capture step
      for the hybridized PCR products. Both enzyme immunoassays utilized
      chemiluminescent detection with Lumiphos 530TM as substrate, after hybridization
      to an internal digoxigenin-labeled probe or a 5' conjugated alkaline phosphatase
      labeled probe. The PCR-ELISA resulted in faster confirmation of the PCR products
      while providing a level of sensitivity comparable to Southern hybridization, and
      has potential for development into an automated method.

PMID- 8880336
TI  - Effects of carbon dioxide on the fate of Listeria monocytogenes, of aerobic
      bacteria and on the development of spoilage in minimally processed fresh endive.
AB  - Minimally processed fresh broad-leaved endive (Cichorium endivia L.) were stored
      at 3 and 10 degrees C in modified atmospheres containing air, 10% CO2/10% O2, 30%
      CO2/10% O2, and 50% CO2/10% O2. The effects of these modified atmospheres on the
      fate of both aerobic bacteria and three strains of Listeria monocytogenes, was
      investigated. Increases in CO2 concentrations significantly reduced the growth of
      the aerobic microflora. The best preservation of the visual quality occurred on
      endive leaves stored in 10% CO2/10% O2, whereas leaves stored in 30% CO2/10% O2
      and 50% CO2/10% O2, and to a lesser extent in air, showed extensive spoilage
      after storage. Listeria monocytogenes was slightly affected at 3 degrees C by the
      modified atmospheres, as compared to air. At 10 degrees C, results varied between
      replicate experiments, but L. monocytogenes generally grew better as the CO2
      concentration was increased. The three test strains behaved in a similar way. In
      conclusion, among the modified atmospheres tested, a modified atmosphere
      containing 10% CO2/10% O2 resulted in improved visual quality of minimally
      processed fresh endive, without a marked effect on the growth of the aerobic
      microflora or of L. monocytogenes.

PMID- 8880337
TI  - Technological and sensorial evaluation of Lactobacillus strains as starter
      cultures in fermented sausages.
AB  - The performance of several lactobacilli strains isolated from naturally fermented
      sausages as starter cultures was evaluated. Microbiological, physical and
      chemical changes, in addition to sensorial aspects were studied. From the 12
      different strains tested, 10 were capable of leading the fermentation in every
      batch throughout the process. The monitoring of the inoculated strains was easily
      carried out by plasmid profiles and by checking the pH rate drop of the sausages,
      which was slower for the non-inoculated lots. Treatment using natural
      fermentation resulted in a product where hydrogen sulphide odours, which could be
      related to the higher content of Enterobacteriaceae throughout the ripening
      process, diminished its overall acceptability. The lots seeded with different L.
      sake strains were found to be low in acid in sensory evaluation, correlating with
      a low lactic acid content. In contrast, the L. plantarum lot gave rise to an
      overacidified product related to having the highest amount of lactic acid at the
      end of the process. As a general rule lactobacilli strains isolated from meat
      origins are good candidates as starter cultures in the manufacture of dry
      fermented sausages and produce satisfactory products depending on the specific
      strains used more than on the species.

PMID- 8880338
TI  - Composition and toxigenic potential of the mould population on dry-cured Iberian
      ham.
AB  - The fungal population on dry-cured Iberian ham can be essential to the
      development of the product's unique characteristics, but health hazards due to
      mycotoxins may be significant. We examined the natural fungal population of
      Iberian hams during ripening at three different locations. Chloroform extracts
      from 59 selected isolates were tested for toxicity to brine shrimp larvae and
      VERO cells, for mutagenicity in the Ames test and for antimicrobial activity
      against Staphylococcus aureus. The diversity of moulds increased during ripening.
      Penicillium commune, Penicillium chrysogenum, Penicillium aurantiogriseum,
      Penicillium expansum and Penicillium echinulatum dominated most of the ripening
      time; however, the Eurotium species, particularly E. herbariorum and E. repens,
      increased in the final product. Using the above tests, most moulds were
      toxigenic. The toxigenic potential of the fungal population increased as the
      processing progressed. To minimize health hazards from uncontrolled fungal
      populations, we identified non toxigenic strains of Penicillium chrysogenum that
      could be used as starters in dry-cured hams.

PMID- 8880339
TI  - Histamine and tyramine production by bacteria from meat products.
AB  - A series of 94 strains of lactic acid bacteria and Micrococcaceae were tested for
      their ability to decarboxylate histidine and tyrosine in a laboratory medium.
      Histamine and tyramine were quantified by using a fluorimetric and a HPLC method.
      There was no significant difference between the results obtained with either
      method. Among the strains tested, only three released histamine. On the other
      hand, all the strains of Carnobacterium produced high concentrations of tyramine
      (2193 micrograms/ml). Some strains of Lactobacillus curvatus and also
      Lactobacillus plantarum showed tyramine production. Micrococcaceae and
      Lactobacillus sake did not produce tyramine.

PMID- 8880340
TI  - Listeria monocytogenes in bovine mastitis. Possible implication for human health.
AB  - During the 23-year period 1972 through 1994 quarter milk samples from 1,132,958
      cows originating from 36199 herds were examined for the presence of Listeria
      monocytogenes. Through the period the reference population amounted to 12,742,600
      cow years and 401,682 herd years. The percentage of cows infected with L.
      monocytogenes varied from 0.01 to 0.1% (mean 0.04%) and of herds with an infected
      cow from 0.2 to 4.2% (mean 1.2%) through the period, showing a low but constant
      level of infection. A comparison of 33 isolates from bovine mastitis and 27 human
      clinical isolates was made by sero- and ribotyping. Serotyping showed that all
      bovine and 17 (63%) of the human isolates belonged to serogroup 1, whereas 10
      (37%) of the human isolates belonged to serogroup 4. Ribotyping using EcoRI as
      restriction enzyme divided the 60 isolates into 16 different types, 7 of which
      were found among both the bovine and human types. The combination of the typing
      methods showed that 26 (79%) bovine and 13 (48%) human isolates shared common
      types. This study showed that a low but constant percentage of Danish dairy herds
      have cows infected with L. monocytogenes and that some of the bovine types could
      be found among types causing human infections.

PMID- 8880341
TI  - Growth and aflatoxin B1 production on olives and olive paste by moulds isolated
      from 'Turkish-style' natural black olives in brine.
AB  - The growth and aflatoxin production of five Aspergillus flavus and two
      Aspergillus parasiticus strains isolated from natural black olives in brine for
      table consumption, fresh whole black olives, fresh damaged black olives and fresh
      black olive paste were examined. Aspergillus flavus NRRL 6555 and A. parasiticus
      NRRL 2999 strains were also studied for comparison. All aflatoxigenic strains
      inoculated onto fresh damaged black olives and fresh black olive paste grew
      extensively but on fresh whole black olives they grew weakly. Strong
      aflatoxigenic strains produced low levels of aflatoxins on fresh whole black
      olives, fresh damaged black olives and fresh black olive paste. Weak
      aflatoxigenic strains did not produce detectable amounts of aflatoxin.

PMID- 8880342
TI  - Mathematical model for the combined effect of temperature and pH on the thermal
      resistance of Bacillus stearothermophilus and Clostridium sporogenes spores.
AB  - Two mathematical models have been studied to establish the relationship between
      the pH, treatment temperature and thermal destruction constant (k) of Bacillus
      stearothermophilus and Clostridium sporogenes spores. The study was carried out
      by heating the spores in mushroom extract acidified with two different acidulants
      (citric acid and glucono-delta-lactone). Among the models studied, the one that
      best described the inactivation was a second order polynomial equation, the
      precision of which depended on the microorganism studied.

PMID- 8880343
TI  - Effect of combined lysozyme and lipase treatment on the survival of Listeria
      monocytogenes.
AB  - The effectiveness of polyphosphates or lipases to increase the lytic activity of
      lysozyme was evaluated both on Listeria monocytogenes suspended in buffer and on
      growing cultures incubated at different temperatures. At 5 degrees C and 37
      degrees C polyphosphates combined with lysozyme did not result in the decrease of
      the number of non-growing L. monocytogenes cells. At the same incubation
      conditions, the addition of lipase to lysozyme significantly enhanced the
      bactericidal activity of lysozyme to an extent determined by pH, NaCl
      concentration and temperature.

PMID- 8880344
TI  - Net carbon flux across subcutaneous adipose tissue after a standard meal in
      normal-weight and insulin-resistant obese subjects.
AB  - OBJECTIVE: To elucidate the alterations in subcutaneous adipose tissue metabolism
      in obesity which affect substrate storage in the fed state, by describing as
      completely as possible the 'metabolic balance sheet' for adipose tissue.
      SUBJECTS: 13 lean people (age: 24-64 years, BMI: 19.3-29.4 kg/m2) and 9 insulin
      resistant obese subjects (age: 38-57 years, BMI: 32.4-56.0 kg/m2). MEASUREMENTS:
      Net flux of eight major substrates and CO2 across subcutaneous adipose tissue in
      vivo before and after eating a standard mixed meal (3.1 MJ, 41% from fat).
      RESULTS: The net flux of total carbon atoms in the 8 substrates and CO2 was
      negative (net export from the tissue) in both groups in the fasting state. After
      the meal it changed rapidly to a positive balance (net substrate storage) in the
      control group and remained positive until 5 h, whereas in the obese group it
      remained negative throughout. The overall carbon balance in adipose tissue
      reflected predominantly the movement of fatty acids in and out of the tissue.
      CONCLUSIONS: The fact that fat storage failed to occur despite elevated plasma
      concentrations of triacylglycerol, glucose and insulin indicates an alteration in
      metabolic regulation at the cellular level which might be called insulin
      resistance. Insulin resistance of fat metabolism may be an adaptation which
      limits further fat deposition, but is maladaptive in terms of risk factors for
      atherosclerosis.

PMID- 8880345
TI  - Visceral adiposity, fasting plasma insulin, and lipid and lipoprotein levels in
      Japanese Americans.
AB  - OBJECTIVE: To examine the associations among visceral and subcutaneous adiposity,
      body-mass-index (BMI), fasting plasma insulin, lipid, and lipoprotein levels.
      DESIGN: Cross-sectional observational study. SUBJECTS: Non-diabetic second-
      (Nisei, n = 290) and third-generation (Sansei, n = 229) Japanese Americans.
      MEASUREMENTS: Intra-abdominal (IAF) and subcutaneous abdominal fat (SAF) area
      were measured using computed tomography. Fasting plasma insulin, lipid, and
      lipoprotein levels were measured using standard methods. RESULTS: Higher fasting
      insulin was significantly related to greater mean IAF and SAF area, plasma
      triglycerides, total HDL and HDL2 cholesterol in men and women of both
      generations. In a multiple linear regression analysis model among Nisei adjusted
      for gender, age, SAF, antihypertensive medication use, smoking, alcohol use, and
      exercise energy expenditure, IAF area and fasting insulin level were
      independently correlated with plasma triglycerides (IAF r = 0.22, fasting insulin
      r = 0.23), total HDL (IAF r = -0.29, fasting insulin r = -0.28), HDL2 (IAF r = 
      0.30, fasting insulin r = -0.27), and HDL3 cholesterol (IAF r = -0.19, fasting
      insulin r = -0.19). Among Sansei, similar associations were seen, except that
      fasting insulin was unrelated to total HDL or HDL3 cholesterol. These effects
      differed by gender in several instances. CONCLUSIONS: Both visceral adiposity and
      fasting insulin level are significantly and independently related to adverse
      levels of lipids and lipoproteins in both generations of nondiabetic Japanese
      Americans. The association between adverse lipid profile and visceral obesity is
      not mediated solely through detrimental effects of intra-abdominal fat deposition
      on fasting insulin level.

PMID- 8880346
TI  - Relationship of obesity and body fat distribution with ceruloplasmin serum
      levels.
AB  - OBJECTIVE: To investigate the influence of obesity and body fat distribution on
      serum levels of ceruloplasmin, a risk factor for myocardial infarction. DESIGN:
      Fasting concentrations of ceruloplasmin, insulin, glucose, lipid pattern
      (cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), blood pressure
      levels, and body fat distribution were determined in a population of non-diabetic
      subjects. SETTING: University Hospital Outpatient Clinic. SUBJECTS: 87
      consecutive individuals (35 men and 52 women), represented by 27 normal weight
      (BMI: < 25.0), 20 overweight (BMI: > 25.0-30.0) and 40 obese (BMI: > 30.0)
      subjects. MEASUREMENTS: Serum insulin levels were quantified by radioimmunoassay,
      plasma glucose and lipid concentrations by enzymatic assays, and serum
      ceruloplasmin by nephelometry. Intra-abdominal thickness was measured by
      ultrasound technique. RESULTS: Ceruloplasmin levels were significantly (P <
      0.001) higher in obese (36.5 +/- 8.60 mg/dl) than in overweight (30.4 +/- 6.17
      mg/dl) and normal weight (29.3 +/- 8.06 mg/dl) subjects. Of several variables
      associated with ceruloplasmin (BMI, waist circumference, WHR, intra-abdominal
      thickness, triglycerides, cholesterol, LDL-cholesterol, insulin), only
      triglycerides (in both men and women) and ultrasound intra-abdominal thickness
      (in women) maintained a significantly independent relationship with this protein
      in multiple stepwise analysis. Moreover, both triglycerides and total cholesterol
      maintained an independent correlation with ceruloplasmin when the data from both
      men and women were pooled together. CONCLUSION: This study indicates that
      patients with central obesity have characteristically higher ceruloplasmin serum
      levels, and that ceruloplasmin concentrations are strongly correlated with serum
      triglyceride and cholesterol levels (in both sexes) and visceral fat accumulation
      (in women), independently of the other associated cardiovascular risk factors
      (insulin and blood pressure levels). Since ceruloplasmin has been shown to
      increase in response to the atherosclerotic inflammatory process, and to promote
      coronarosclerosis, the determination of serum ceruloplasmin in subjects with
      central obesity might be a useful tool to identify patients with the highest risk
      for myocardial infarction.

PMID- 8880347
TI  - Erythrocyte rheological changes in obese patients: influence of hyperinsulinism.
AB  - OBJECTIVE: To investigate the rheological properties of RBC in obese subjects and
      the factors associated with their changes. SUBJECTS: Two consecutive studies of
      non diabetic obese subjects. MEASUREMENTS: Filtration index of RBC using the
      Hanss hemorheometer, RBC filterability using a cell transit time analyser and RBC
      aggregation measured on the Myrenne aggregometer. RESULTS: In both studies an
      increase in the filtration index of RBC, namely a reduction in their
      deformability, was found. In the first study the filtration index correlated
      negatively with hematocrit and positively with plasma C peptide levels. In the
      second study RBC filterability was also studied by the cell transit time analyzer
      in which there is no aggregate formation. The RBC transit time was not found to
      be different in the obese patients and in the controls, but RBC aggregation was
      increased and correlated significantly with body weight and BMI. RBC aggregation
      worsened after four days of hypocaloric diet. CONCLUSION: (1) obesity,
      independently of the other cardiovascular risk factors, is associated with
      significant changes in RBC rheology; (2) these changes are probably related for
      the most part to plasma factors, possibly via hyperinsulinemia, even if changes
      in the chemical composition of the RBC membrane are not excluded, (3) RBC
      aggregation worsens during the first days of a hypocaloric diet; (4) rheological
      changes in RBC seem to be another component of the insulin resistance syndrome.

PMID- 8880348
TI  - Frequency of 'obesity' in medical records and utilization of out-patient health
      care by 'obese' subjects in Germany. An analysis of health insurance data.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of the diagnoses
      'overweight' or 'obesity' in medical records and to examine the utilization of
      the out-patient health care system by 'obese' subjects. DESIGN: All claims-cards,
      prescriptions and other diagnosis-carrying medical certificates from 1990 of a
      representative sample of members of a large local health insurance were collected
      and analyzed anonymously in a patient-related approach. SUBJECTS: A 5% random
      sample (n = 6085) of all members of the general local health insurance (AOK) in
      the city of Dortmund, Germany. MEASUREMENTS: The percentage of subjects carrying
      the diagnosis of 'overweight' and/or 'obesity' was determined. In addition, the
      utilization of medical services and the presence of comorbid conditions in the
      documents of the AOK was recorded. RESULTS: A total number of 377 'obese'
      subjects was identified corresponding with a prevalence rate of 6.2%. Among
      those, more women than men carried one of these diagnoses (240 vs 137, 7.3% vs
      4.9%, p < 0.01). In comparison with an age- and sex-matched control group (n =
      1131) the 'obese' subjects had significantly more practice contacts (25.7 vs
      17.5/year, p < 0.01) and received more medical services (64.2 vs 43.0/year, p <
      0.01), including more prescriptions (20.9 vs 15.5/year, p < 0.01). Furthermore,
      the 'obese' subjects had more additional diagnoses indicating a higher
      comorbidity and received more drugs for diseases and complications which are
      characteristic of obesity but also for other diseases. CONCLUSION: This data
      suggests that in view of its high prevalence in Germany obesity is perceived and
      documented by health professionals only in a minority of affected subjects
      indicating that this disorder is considerably under-estimated. It is also evident
      from the data that obesity is mainly noticed in those who have other serious
      health problems.

PMID- 8880349
TI  - Power spectral analysis of heart rate variability in obese subjects: evidence of
      decreased cardiac sympathetic responsiveness.
AB  - OBJECTIVE: To investigate changes in sympathetic nervous system function in
      obesity. DESIGN: Cross-sectional clinical study. SUBJECTS: 18 middle-aged obese
      patients (43-55 years, BMI > 33 kg/m2) and 26 age- and sex-matched normal-weight
      controls (44-56 years, BMI < 26 kg/m2). MEASUREMENTS: Post-synaptic sympathetic
      response studied by power spectral analysis of heart rate variability at rest and
      during sympathetic stimulus obtained through passive head-up tilt. Spectral
      analysis comprised two frequency domain components: high-frequency power (HF),
      reflecting parasympathetic activity and low-frequency power (LF), in particular
      the LF: HF ratio, reflecting sympathetic function. Pre-synaptic sympatho-adrenal
      function was assessed by measurement of 8.00 am plasma noradrenaline. RESULTS:
      Obese patients had significantly lower spectral indexes of sympathetic response
      and higher spectral markers of parasympathetic activity than nonobese subjects
      both at rest (25.9 +/- 3.5 vs 38.6 +/- 1.7 LF NUs, P < 0.001) and after tilt
      (0.98 +/- 0.40 vs 2.30 +/- 0.39 LF: HF, P < 0.05; 62.7 +/- 6.9 vs 41.1 +/- 4.9 HF
      NUs, P < 0.05). By contrast, the obese subjects had higher noradrenaline levels
      (289.32 +/- 27.40 vs 159.80 +/- 19.20 pg/ml, P < 0.001). No relation was found
      between these neuroautonomic indexes and body mass index. CONCLUSION: Obese
      subjects seem to have increased pre-synaptic sympatho-adrenal function but a
      depressed end-organ cardiovascular response.

PMID- 8880350
TI  - Preliminary results of triple therapy for obesity.
AB  - OBJECTIVE: To evaluate the effectiveness of triple therapy in treatment of simple
      obesity. SUBJECTS: Forty-five cases of simple obesity with a body mass index
      (BMI) above 30 kg/m2 and percentage of body fat more than 25% in males, and 30%
      in females were collected. Subjects were composed of 8 males and 37 females
      ranging in age from 16 to 70 years old with a mean age of 33.8 years. METHODS:
      The triple therapy for obesity included weekly auricular acupuncture, diet
      control and aerobic exercise counseling for eight weeks. The reduction in body
      weight and body fat were measured upon just completing the therapeutic course.
      The changes of body weight in follow-up at one month and one year later were also
      analyzed respectively. RESULTS: The results showed a 4.4 +/- 2.9 kg reduction in
      body weight and a 5.6 +/- 3.0% reduction in body fat after completing the
      treatment course. Five cases had their body weight reduced to within the normal
      range, 18 cases showed a marked effect (body weight reduced by more than 5 kg and
      body fat reduced more than 5%), 16 cases were considered effective (body weight
      reduced by 2-5 kg and body fat reduced by 1-5%), and 6 cases were considered to
      be ineffective (body weight reduced by less than 2 kg and body fat reduced by
      less than 1%). The rate of effectiveness was 86.7%. The rate of body weight
      rebound (weight regained more than 1.5 kg) was 6.7% and 18.9% one month and one
      year later, respectively. The effectiveness of weight reduction was significant
      correlated with the compliance of participants with each therapeutic method, but
      not with age. No special side effects were noted during or after the treatment
      except for two cases who had intolerable pain when receiving auricular
      acupuncture. CONCLUSION: The triple therapy resulted in a satisfactory body
      weight reduction and a good maintenance of the target weight after treatment.
      Furthermore, more frequent aerobic exercise during the treatment course
      contributed greatly to body weight reduction and maintenance, as indicated by the
      correlation analysis.

PMID- 8880351
TI  - Adipose tissue extraction of circulating insulin in anaesthetized Zucker obese
      rats.
AB  - OBJECTIVE: To determine whether adipose tissue removes a significant proportion
      of circulating insulin in the obese rat in vivo. DESIGN: Blood samples were
      obtained from the carotid artery and the venous side of hind leg muscle,
      epididymal fat pads and liver (portal and suprahepatic veins), they were used for
      estimation of insulin disappearance across the tissue. SUBJECTS: Anaesthetized
      Zucker lean (Fa/?) and obese (fa/fa) adult male rats. MEASUREMENTS: Blood flow,
      glycaemia and insulinaemia. RESULTS: In lean rats, the liver accounted for
      practically all insulin extraction (498 +/- 149 fmol.s-1), removing more than
      half of the portal insulin in a single pass. In the obese rats, the liver
      extracted a similar amount in absolute terms (397 +/- 108 fmol.s-1), representing
      only 16% of portal insulin. In the hind leg muscle of both groups and in the
      adipose tissue of lean rats, insulin balances were not different from zero; but
      in obese rats, adipose tissue extracted a similar amount of insulin (405 +/- 127
      fmol.s-1) to that removed by the liver. CONCLUSIONS: In the Zucker obese rat,
      peripheral adipose tissue removes as much insulin from the blood as the liver
      does, in contrast with lean rats, in which the latter is responsible for
      practically all insulin extraction.

PMID- 8880352
TI  - Influences of body weight, body composition, and substrate oxidation rate on
      resting postabsorptive glucose production and gluconeogenesis.
AB  - OBJECTIVE: To determine the influence of body weight, fat mass, and fat
      distribution on resting endogenous glucose production in healthy lean and
      overweight individuals. DESIGN: measurements were performed in the resting
      postabsorptive state in individuals receiving an unrestricted diet. SETTING:
      Institute of Physiology of Lausanne University. MEASUREMENTS: resting post
      absorptive glucose production, glycogenolysis and gluconeogenesis; resting energy
      expenditure and net substrate oxidation. RESULTS: Endogenous glucose production
      was positively correlated with body weight, lean body mass, energy expenditure
      and carbohydrate oxidation. Gluconeogenesis was positively correlated with net
      lipid oxidation and energy expenditure, and negatively correlated with net
      carbohydrate oxidation. No correlation with body fat or fat distribution was
      observed. CONCLUSIONS: Gluconeogenesis shows a large interindividual variability.
      Net lipid oxidation and not body fat appears to be a major determinant of
      gluconeogenesis.

PMID- 8880353
TI  - The relationship between components of infant energy expenditure and childhood
      body fatness.
AB  - OBJECTIVE: To investigate whether any component of infant energy expenditure is
      related to fatness in early childhood, and whether infant fatness is related to
      childhood variables. DESIGN: Longitudinal investigation of infants studied at 12
      weeks and followed up at 2.5 to 3.5 years of age. SUBJECTS: 30 healthy full-term
      infants selected from the general population. MEASUREMENTS: Sleeping metabolic
      rate, total energy expenditure, anthropometry and behaviour at 12 weeks;
      anthropometry, body composition and behaviour in follow-up. RESULTS: Energy
      expenditure at 12 weeks (minimal metabolism, total energy expenditure, energy
      expended on physical activity, behaviour) showed no relationship with later
      fatness. Infant fatness (skinfold thicknesses and percentage fat) showed in
      contrast a strong relationship with childhood fatness. Infant fatness also
      predicted childhood behaviour. CONCLUSIONS: These data do not support the theory
      that reduced energy expenditure in early infancy is related to later fatness.
      However, infant fatness influences both later fatness and activity patterns.

PMID- 8880354
TI  - Recall of body weight and body size estimation in women enrolled in the breast
      cancer detection and demonstration project (BCDDP).
AB  - OBJECTIVE: To examine the relationship between body mass index (BMI) and
      pictorial representations of body size in women from young adulthood to late mid
      life. DESIGN: Retrospective, descriptive study of BMI and pictorial estimation of
      body size. SUBJECTS: 5,807 women age 33-77 years enrolled in the National Cancer
      Institute's and American Cancer Society Breast Cancer Detection and Demonstration
      Project (BCDDP). MEASUREMENTS: Body weight and height were measured in 1973. In
      1977, a subset of the cohort recalled their usual height and weight at 10 y
      intervals starting at age 20. In 1987, subjects reported their usual and current
      weight and selected one of nine pictorials best representing their body size at
      ages 15, 25, 40, 50 and +60 y. RESULTS: For the cohort, and among White women,
      Pearson correlations between recalled BMI (Kg/M2) and pictorials for each decade
      ranged from 0.62-0.67 and was 0.80 for current BMI and current pictorial. The
      range of correlations between pictorials and recalled BMI for other race/ethnic
      groups were 0.72-0.87 (Black), 0.53-0.75 (Hispanic) and 0.28-0.87 (Asian). Among
      a subset of women with data on measured BMI, recalled BMI and pictorials at
      specific ages, the correlation between pictorials and measured BMI was 0.75,
      compared to the correlation between recalled BMI and measured BMI which was 0.89.
      CONCLUSION: Correlations are higher between recalled BMI and measured BMI
      compared to the correlation between pictorials and measured BMI. Therefore,
      estimates of body size by pictorials alone may not be appropriate for
      epidemiological investigations. Alternate uses of pictorials may include
      assessment body weight in low literate populations or in instances where body
      weight is not or has not been measured.

PMID- 8880356
TI  - Measuring body fatness in children and young adults: comparison of bioelectric
      impedance analysis, total body electrical conductivity, and dual-energy X-ray
      absorptiometry.
AB  - OBJECTIVE: To determine the level of agreement for body fatness measurements
      among four body composition measurement techniques. SUBJECTS: 99 healthy children
      and young adults (63 males, 36 females; ages: 5-22 y) MEASUREMENT: Bioelectrical
      impedance analysis (BIA), bioelectrical impedance spectroscopy (BIS), total body
      electrical conductivity (TOBEC), and dual-energy X-ray absorptiometry (DXA)
      measurements of body fat mass, and its percentage of body weight (% Fat).
      RESULTS: Estimates for body fat mass and % Fat were highly correlated (r = 0.72
      0.97, P < 0.001) among the four methods. However, a Bland-Altman comparison among
      the estimates indicated significant differences between methods. The mean
      differences between methods for body fat ranged from -0.30 +/- 6.7 kg to 4.2 +/-
      2.7 kg. Differences for % Fat ranged from 0.8% +/- 3.5% to -9.9% +/- 5.2%.
      Fatness classification of an individual as normal, overweight, or obese on the
      basis of his/her % Fat was significantly method dependent. CONCLUSIONS: The lack
      of interchangeability for fatness classification makes it difficult to ensure
      that similar groups of subjects can be accurately selected for the same true fat
      content or % Fat range when different methods are used. Furthermore, this
      limitation may restrict comparison of findings among different studies, such as
      in weight reduction, exercise, or therapy programs, when the subjects were not
      originally classified using the same measurement methods. That is, the reported
      values and changes for body fat or % Fat appear to be highly method dependent.

PMID- 8880355
TI  - Intra-abdominal adipose tissue, physical activity and cardiovascular risk in pre-
      and post-menopausal women.
AB  - OBJECTIVE: Determine whether the independent inter-relationships between intra
      abdominal adipose tissue (IAF) cardiovascular disease (CVD) risk, and physical
      activity (PA) support the hypothesis that the beneficial effect of PA of CVD risk
      is mediated through the effects of activity on IAF. DESIGN: Cross-sectional.
      SUBJECTS: 220 female Caucasian women 17-77 years old. MEASUREMENTS: Computed
      tomography IAF and subcutaneous abdominal adipose tissue (SAF), percent fat, CVD
      risk factors (blood lipids and blood pressure) and PA using the Baecke
      questionnaire. RESULTS: Zero-order correlations indicated that IAF, SAF, percent
      fat, age, menopausal status (MS), and all 4 of the PA indexes were consistently
      related to CVD risk. After adjusting for age, MS, SAF, and percent fat, IAF was
      negatively related to PA (r2 = 0.04), indicating that more active women had
      relatively small IAF compared to other fat depots. After adjusting for IAF, MS,
      and age none of the PA indexes were related to any of the CVD risk factors except
      cholesterol/HDL ratio (partial r2 = 0.02). However, after adjusting for PA, MS
      and age, IAF was related to all CVD risk factors except cholesterol (partial r2 =
      0.03-0.23). CONCLUSION: These results support the hypothesis that PA may obtain
      at least part of its effect on CVD risk by reducing IAF.

PMID- 8880357
TI  - Microcalorimetric and biochemical investigations of thermogenesis and metabolic
      pathways in human white adipocytes.
AB  - OBJECTIVE: Validation of a novel culture technique for human white adipocytes,
      facilitating direct microcalorimetry and simultaneously performed biochemistry
      for 3 days. DESIGN: Subcutaneous adipocytes were cultured in a 3-dimensional
      matrix of agarose gel. Biochemical measures were obtained every 24 h, while
      thermogenesis was continuously monitored for 72 h. DNA content of the cultures
      served as reference. SUBJECTS: 73 men and women undergoing uncomplicated surgery.
      MEASUREMENTS: Cell viability (LDH release), total cellular thermogenesis, oxygen
      consumption, glycolysis, lipolysis (basal, catecholamin-stimulated)
      triglyceride/free fatty acid substrate cycle, adenine nucleotides, insulin
      induced thermogenesis. RESULTS: LDH release was 0.4% of total LDH per hour.
      Cellular ATP, ADP and AMP (3.77, 0.39 and 0.06 nmol/microgramDNA, resp.) were
      constant. The rates of glucose consumption, lactate and pyruvate production and
      basal glycerol release (56.4, 43.1, 2.7 and 28.1 nmol/microgramDNA.h, resp.) were
      stable during 72 h. Isoprenaline (1 microM) enhanced lipolytic rate by the same
      extent at any time of the study (glycerol release 67.8 nmol/microgramDNA.h). FFA
      release (initially 26.0 nmol/ microgramDNA.h) declined during the experiment, due
      to an increase of reesterfication rate. Unstimulated heat production was 6.5
      microW/microgramDNA, 68% of which were of oxidative origin. Insulin (0.1 microM)
      induced thermogenesis was 8.8 microW/ microgramDNA. CONCLUSION: The results were
      in accordance with data from human white adipocytes in suspensions. However, in
      contrast to fat cell suspensions, gel cultured adipocytes were viable for 3 days
      without metabolic alterations.

PMID- 8880358
TI  - Ultrasonographic intra-abdominal depth and its relation to haemostatic factors in
      healthy males.
AB  - OBJECTIVE: To examine the relationship of intra-abdominal fat to plasma
      haemostatic factors. SUBJECTS: 60 healthy, predominantly nonobese, male
      volunteers aged 38 years. MEASUREMENTS: Anthropometry, sonographic intra
      abdominal depth (IAD), as an indicator of intra-abdominal fat, plasma lipids,
      plasma insulin (at fasting and after glucose load), various plasma haemostatic
      factors. RESULTS: Sonographic IAD correlated positively with plasma fibrinogen (r
      = 0.33; P < 0.01), PAI-1 activity (r = 0.52; P < 0.0001) and antigen (r = 0.32; P
      < 0.05), and negatively with t-PA activity, at baseline and after stasis (r = 
      0.28 and r = 0.31; P < 0.05). Factor VII levels did not correlate significantly
      with sonographic IAD. Haemostatic variables were also closely associated with
      BMI, plasma triglyceride and insulin concentrations. Most correlations of
      haemostatic factors with IAD disappeared after adjustment for either BMI or
      insulin or triglycerides, except PAI-1 levels which maintained a significant
      association even after simultaneous adjustment for all potential confounders.
      CONCLUSIONS: These results, obtained by sonography, confirm our previous findings
      of significant associations of haemostatic variables with visceral fat
      accumulation by using computed tomography, and highlight the role of the intra
      abdominal fat as an independent predictor of PAI-1 activity.

PMID- 8880359
TI  - Is elevated heart rate part of the insulin resistance syndrome?

PMID- 8880360
TI  - Lipoproteins and cholesterol ester transfer protein in obese women on a very low
      calorie diet.

PMID- 8880361
TI  - Suppression of EEG rhythmic frequencies during somato-motor and visuo-motor
      behavior.
AB  - In a previous study of simulated vehicle performance we found that stationary
      visual attention and body movements alone produced selective effects on
      topographic EEG frequency patterns. In the present study we focus on an expanded
      set of these task components. EEG, EOG and ECG data were recorded from 21
      subjects during instructed driving movements and during visual scanning tasks
      ranging from a stationary to a rapidly moving simulated driving display. Spectral
      analysis was calculated on ten 2-Hz, partially overlapped frequency bands between
      6 and 17 Hz. Body movements produced a selective bilateral suppression of 11-15
      Hz activity localized to medial somatosensory cortex, while both slow and rapid
      visual scanning tasks produced a similar bilateral suppression of 11-15 Hz
      activity localized to temporo-parietal sites. A generalized suppression of 7-11
      Hz activity was also found during the fastest visual scanning task. There were no
      significant differences in ECG between tasks. Other human and animal findings
      consistent with these functional observations are discussed.

PMID- 8880362
TI  - Detecting simulated amnesia for autobiographical and recently learned information
      using the P300 event-related potential.
AB  - To investigate whether the P300 (P3) event-related potential (ERP) can be used as
      an index of the intactness of recognition memory in subjects trying to simulate
      amnesia, two groups of subjects (n = 12 and n = 15) were instructed to simulate
      amnesia and one group of control subjects (n = 14) did not simulate amnesia while
      taking three recognition tests, during which ERPs were recorded. The three tests
      consisted of three different types of memory items: (1) the subject's birthday
      (birth), (2) the experimenter's name (name), (3) a word list of 14 nouns (words).
      The memory item was presented in a random series with other, similar in type, non
      memory items. In group tests, memory items evoked larger amplitude P3s than non
      memory items (p < 0.001). Within-subjects tests were used to determine whether
      the P3 amplitude in response to memory items was larger than the P3 amplitude in
      response to non-memory items for each individual. There was no difference between
      the sensitivity of the best within-subjects tests for amnesia simulators (birth =
      0.9, name = 0.85, words = 0.53) versus non-simulators (birth = 1.0, name = 0.81,
      words = 0.5) averaged across the three test types. This suggests that P3 used as
      an index of the intactness of recognition memory may be useful in cases of
      suspected malingering.

PMID- 8880363
TI  - Developmentally advanced EEG alpha power in gifted male and female adolescents.
AB  - An electroencephalographic (EEG) study of gifted and average ability male and
      female adolescents, as well as college students of both sexes, was conducted to
      investigate further the relative contributions the left and right cerebral
      hemispheres during an eyes open (baseline) task in all groups. A total of 90
      subjects had baseline EEG recorded in three groups with equal numbers of males
      and females: 30 gifted adolescents, 30 average ability adolescents, and 30
      college-age subjects. Overall alpha power (8-12 Hz resting potential) was
      significantly greater in average ability subjects compared to both college-age
      subjects. Moreover, there were no significant differences in overall alpha power
      between college-age and gifted adolescent subjects. However, college-age and
      gifted adolescent subjects had different RH/LH patterns of activation such that
      at temporal and parietal locations college-age and gifted adolescent subjects had
      greater LH alpha power levels whereas gifted adolescents had greater RH alpha
      power. These findings suggest that gifted adolescents may have a developmentally
      enhanced state of brain activity, one that more closely resembles that of college
      age adults to whom they also resemble in terms of cognitive development.

PMID- 8880364
TI  - P300 from one-, two-, and three-stimulus auditory paradigms.
AB  - P300 event-related potentials (ERPs) from 1-, 2-, and 3-tone oddball paradigms
      were elicited and compared from the same subjects. In the 1-tone paradigm, only a
      target tone was presented, with the standard tone replaced by silence. The 2-tone
      paradigm was a typical oddball task, wherein the target and standard tones were
      presented every 2.0 s in a random order with a target-tone probability of 0.10.
      In the 3-tone paradigm, in addition to the infrequent target (p = 0.10) and the
      frequent standard (p = 0.80), infrequent nontarget tones (p = 0.10) also were
      presented. The subject responded with a button press only to the target stimulus
      in each task. The target stimulus in each paradigm elicited a P300 component with
      a parietal maximum distribution. No P300 amplitude differences were found among
      paradigms, although peak latency from the 1-tone paradigm was shorter than those
      from the other two tasks. Both P300 peak amplitude and latency demonstrated
      strong positive correlations between each pair of paradigms. The results suggest
      that P300 was produced by the same neural and cognitive mechanisms across tasks.
      The possible utility of each paradigm in clinical testing is discussed.

PMID- 8880365
TI  - The Simon effect and its reversal studied with event-related potentials.
AB  - The Simon effect (slower RT when stimulus and response locations do not match,
      stimulus location being irrelevant) and its reversal, were investigated using
      P300 latency and motor-related potentials. Stimuli were one of two colors, and
      response keys were two buttons with color labels that changed randomly in every
      trial. Depending on the stimulus-response (S-R) mapping instructions, subjects
      pressed the same-color key or the alternate-color key. Behavioral measures showed
      a Simon effect in same- and a reverse Simon effect in alternate-color mapping
      contradicting the display-control arrangement correspondence and the S-S
      compatibility, as explanations for the reverse Simon effect. P300 latencies
      followed the same pattern as RT, i.e. they were influenced by the S-R mapping,
      suggesting that this measure does not index the duration of the stimulus
      evaluation, but response selection processes. The motor-related potentials
      demonstrated response activation based on stimulus location, also supporting
      response- interference interpretations of the Simon effect.

PMID- 8880366
TI  - P300, stimulus intensity, modality, and probability.
AB  - Auditory and visual stimulus intensity were manipulated factorially with target
      probability to assess the influence of these variables on the P300 component of
      the event-related brain potential (ERP). Increases in stimulus intensity produced
      reliable increases in P300 amplitude and decreases in peak latency for both
      modalities that were additive with target stimulus probability effects. Similar,
      somewhat weaker stimulus intensity effects also were observed for the N100, P200,
      and N200 components. The findings suggest that stimulus intensity contributes to
      both P300 amplitude and latency measures in important ways and are discussed in
      relation to the use of ERPs in applied contexts.

PMID- 8880367
TI  - A guide for applying principal-components analysis and confirmatory factor
      analysis to quantitative electroencephalogram data.
AB  - Principal-components analysis (PCA) has been used in quantitative
      electroencephalogram (qEEG) research to statistically reduce the dimensionality
      of the original qEEG measures to a smaller set of theoretically meaningful
      component variables. However, PCAs involving qEEG have frequently been performed
      with small sample sizes, producing solutions that are highly unstable. Moreover,
      solutions have not been independently confirmed using an independent sample and
      the more rigorous confirmatory factor analysis (CFA) procedure. This paper was
      intended to illustrate, by way of example, the process of applying PCA and CFA to
      qEEG data. Explicit decision rules pertaining to the application of PCA and CFA
      to qEEG are discussed. In the first of two experiments, PCAs were performed on
      qEEG measures collected from 102 healthy individuals as they performed an
      auditory continuous performance task. Component solutions were then validated in
      an independent sample of 106 healthy individuals using the CFA procedure. The
      results of this experiment confirmed the validity of an oblique, seven component
      solution. Measures of internal consistency and test-retest reliability for the
      seven component solution were high. These results support the use of qEEG data as
      a stable and valid measure of neurophysiological functioning. As measures of
      these neurophysiological processes are easily derived, they may prove useful in
      discriminating between and among clinical (neurological) and control populations.
      Future research directions are highlighted.

PMID- 8880368
TI  - Race and sex differences in cardiovascular recovery from acute stress.
AB  - To evaluate the effects of race and gender on recovery, i.e. the relative return
      to baseline after a stress challenge, cardiovascular and catecholamine measures
      were examined before, during and after two standardized laboratory stressors (a
      speaking and a mirror tracing task) in a group of 85 Black and White men and
      women (mean age 35.6 years, range 20 to 52). For the speech task, White men
      showed the least systolic (p < 0.025) and diastolic (p < 0.05) blood pressure
      recovery as compared to Black men and women. For the mirror star tracing task,
      total peripheral resistance (p < 0.03) recovery was least for Whites as compared
      to Blacks and heart rate (p < 0.04) recovery was least for White women as
      compared to Black women and men. There were no significant group effects in terms
      of catecholamine recovery from either task. The findings extend prior studies on
      race and gender by suggesting that these same characteristics affect recovery
      from stressors.

PMID- 8880369
TI  - Response latencies and event-related potentials during the gap paradigm using
      saccadic responses in human subjects.
AB  - An experiment was conducted in naive human subjects to measure the time benefits
      of the latencies of saccadic eye movements to peripheral targets when the offset
      of a central fixation point precedes the switching on of the peripheral target by
      200 ms. Naive subjects produced a shift advancement of the eye movement latencies
      to the targets with respect to when there is no such temporal gap.
      Simultaneously, the event-related potentials produced by visual stimuli and
      saccadic eye movements were recorded. The switching on of the central fixation
      point induced a negative component that could be considered a contingent negative
      variation. Subsequently, in the control non-gap condition visual evoked
      potentials and P300 appear. The temporal gap paradigm induced offset visual
      evoked potentials and a frontal negativity; it also induced a higher P300 than
      the non-gap condition. The saccadic ERPs also showed a frontal negativity
      preceding the saccade during the gap condition. The results suggest that fast
      regular saccades during the gap paradigm occur by a priming of premotor and motor
      frontal circuits indexed by the recorded negativity during the gap paradigm.

PMID- 8880370
TI  - Effects of smoking and telic/paratelic dominance on the contingent negative
      variation (CNV).
AB  - Concepts from reversal theory, a general theory of motivation, emotion and
      action, have recently been shown to be relevant to smoking behavior and smoking
      cessation. One relevant concept is that of telic and paratelic dominance.
      Individuals who are paratelic-dominant are playful, spontaneous, and prefer high
      arousal seeking. Those who are telic-dominant are serious, tend to plan ahead,
      and prefer low arousal. This led to the hypothesis that smoking might increase
      the amplitude of the contingent negative variation (CNV) in paratelic-dominant
      smokers more than in telic-dominant smokers. CNV was obtained using a Go/NoGo
      reaction time task with a 2 s S1-S2 interval and variable intertrial intervals.
      S1 indicated whether the subject was to respond to S2 or not. Errors were
      punished with a burst of white noise. Subjects performed the CNV task three
      times: after being deprived of smoking for at least 4 h; after sham smoking; and
      after smoking a cigarette of their own brand. Telic-dominant subjects differed
      from paratelic-dominant subjects in the relative amplitude of early (1 s) and
      late (2 s) components of the CNV. Smoking did not differentially affect the
      dominance groups unless gender was taken into account, and the most striking
      interactions between smoking and dominance groups were noted for the NoGo trials.
      As expected, smoking decreased the amplitude of the early component of the NoGo
      CNV for telic-dominant women, but increased it for paratelic-dominant women; no
      significant differences were found for the late component. In men, smoking
      increased the late CNV more for telics than for paratelics, while smoking did not
      differentially affect the early component.

PMID- 8880371
TI  - Information processing in working memory and event-related brain potentials.
AB  - Information processing in working memory was investigated in a paradigm with a
      pseudo-random sequence of visually presented consonants. The subjects' task was
      to memorize seven sequentially presented letters per trial and to recall the
      sequence (MEMORY task). Even-related potentials (ERPs) were selectively averaged
      for each of the seven positions of consonant presentation within a trial. The
      later a consonant was presented within a trial the smaller the P300 amplitude
      elicited by the consonant. The number of recall errors increased, however, from
      first to last presentation position. In a control task identical to the MEMORY
      condition consonant were presented. To limit the working memory load to one
      element, subjects had to count the number of letters within trials showing a
      specific physical criteria. P300 amplitude did not depend on presentation
      position. P300 was shown to covary with the amount of processing resources
      available for a task. We assume that increasing working memory load consumes
      processing resources that are not available for the processing of the incoming
      stimuli presented later in the trial.

PMID- 8880372
TI  - EEG correlates of exercise dependency.
AB  - Jacobs' (1986) proposition that dependency is the result of two sets of
      predisposing factors (one of which is either an excessively depressed or excited
      resting physiological state) was examined in relation to exercise dependency by
      investigating EEG characteristics of subjects committed to fitness regimes. EEG
      records of three groups of subjects who differed in terms of degree of dependency
      were studied under resting conditions both pre- and post-exercise. The results
      indicated that although there were no differences between groups in terms of
      relative power in each of five EEG bandwidths covering the range 0 to 30 Hz, the
      power distribution within the alpha (7.5-13 Hz) bandwidth was significantly
      different for high dependent and non-dependent groups under both the pre- and
      post-exercise conditions. While the distribution was skewed toward the lower
      alpha frequencies for the low dependent group, it was skewed toward the higher
      frequencies for the high dependent group with the distribution for a group with
      high involvement but low dependency falling between these extremes. This finding
      is taken as partial support for Jacobs' notion that dependency is associated with
      greater physiological excitation in the resting state.

PMID- 8880373
TI  - Electrodermal lability and hypertension.
AB  - Thirty-nine (39) middle-aged subjects with mild to moderate hypertension (WHO
      stages I-II) and 35 healthy normotensive controls from a community sample
      participated in this psychophysiological study, the aim of which was to study
      whether the electrodermal lability as an indicator of increased sympathetic
      activity is related to hypertension. Resting blood pressure was measured by using
      a mercury sphygmomanometer. Electrodermal activity was recorded with a constant
      voltage circuit. Bipolar skin electrodes were placed on the palmar side of the
      middle phalanges of the index and middle fingers of both hands. Six years after
      the electrodermal measurements, the possible use of reimbursed antihypertensive
      medication was checked in both groups, and blood pressure re-measured in the
      control group. Multivariate analysis controlling for age, gender and body mass
      showed that the electrodermal lability was increased in the hypertensive as
      compared to the normotensive group. This supports the hypothesis that the
      sympathetic nervous system tonus is increased at least, in some middle-aged
      subjects with mild to moderate hypertension.

PMID- 8880374
TI  - Preliminary evidence that daily changes in frontal alpha asymmetry correlate with
      changes in affect in therapy sessions.
AB  - Frontal EEG alpha asymmetry was recorded from five depressed outpatients during
      early EEG biofeedback sessions. Mood was assessed prior to and after each
      session, and affect change scores were also derived by subtracting pre-session
      from post-session scores. Alpha magnitude was obtained via Fast Fourier
      Transforms. All scores (EEG alpha asymmetry and affect) were converted to
      deviation scores by subtracting each patient's daily score from that patient's
      mean across all available sessions for that patient. Pearson correlations were
      then computed between asymmetry and affect scores using the deviation scores
      combined over patients. There was little evidence of correlation between day-to
      day asymmetry score and any single affect score. Strong correlations were
      obtained, however, between asymmetry score and affect change score and, in
      particular, between asymmetry score and change in positive affect.

PMID- 8880375
TI  - The mast cell: a neuroimmunoendocrine master player.
AB  - This review of the literature on mast cells (MC) suggests that when activated
      they may play a central role in disease syndromes with a neural, immune and
      endocrine component exacerbated under stress. After a discussion of their
      biology, differential secretions and interaction with neurons, the effect of
      stress in causing MC degranulation is emphasized. The importance of MC in
      syndromes such as migraine, multiple sclerosis, interstitial cystitis and
      irritable bowel syndrome is assessed, along with possible therapeutic
      possibilities with compounds that inhibit MC activation.

PMID- 8880377
TI  - Convulsions and death induced in rats by Tween 80 are prevented by capsaicin.
AB  - Two or three minutes after intracerebroventricular (i.c.v.) injection of Tween 80
      plus ethanol as vehicles for capsaicin, strong convulsive movements occurred in
      the treated rats; they twisted and turned, dashed themselves against their cage
      and all died. Tween 80 in saline without ethanol also produced convulsions and
      death in all the rats treated. Capsaicin dissolved in the vehicle seemed to
      furnish protection against such death. Moreover, when capsaicin in Tween 80 was
      administered i.c.v. 10 min before the Tween vehicle it prevented the death which
      would have been caused by the i.c.v. vehicle. Thus a new effect is added to those
      already discovered in the numerous pharmacological studies on capsaicin.

PMID- 8880376
TI  - Immunobiological diagnosis of tropical ocular diseases: Toxocara, Pythium
      insidiosum, Pseudomonas (Burkholderia) pseudomallei, Mycobacterium chelonei and
      Toxoplasma gondii.
AB  - Of the sera obtained from 18 patients with ocular diseases comprising ocular
      larva migrans (OLM), Toxoplasma gondii, Mycobacterium chelonei, Pythium
      insidiosum bacteria and tumour, 3 sera were positive for Toxocara antibody at the
      titre over 1/1600 ELISA. All 3 of these sera came from males with unilateral
      grayish fundi. We demonstrated the value of the direct immunofluorescent assay
      (DIFA) on vitreous specimens from 7 cases of Toxoplasma retinitis. One vitreous
      specimen under electronmicroscopic examination revealed bradyzoites of T. gondii.
      In addition, a few cases of keratoconjunctivitis/ corneal ulcer with
      endophthalmitis, due to P. insidiosum, Ps. pseudomallei and Mycobacterium
      chelonei, were also diagnosed.

PMID- 8880378
TI  - Muscle cell and oxidative damage in aging: a century of hypothesis and personal
      contribution.

PMID- 8880379
TI  - Galactosaminoglycuronglycan sulfate in erosive osteoarthritis of the hands: early
      diagnosis, early treatment.
AB  - This study examined the effect of an oral chondroprotective drug,
      galactosaminoglycuronglycan sulfate (GAGs), on the evolution of erosive
      osteoarthritis of the hands (EOA). Twenty-four patients affected with EOA of the
      hands were evaluated. The patients had painful, frank arthritis of DIP and PIP
      joints; X-rays reduced joint space; X-rays central joint erosions; positive joint
      scintiscan, in absence of other inflammatory and erosive arthropathies. Twelve
      patients were treated with a chondroprotective drug, GAGs 800 mg/ die; twelve
      patients were the control group. The results at two years documented that the
      GAGs treatment influenced certainly joint pain and doubtfully bone scintiscan in
      EOA.

PMID- 8880380
TI  - Analysis of PrPc mRNA by in situ hybridization in brain, placenta, uterus and
      testis of rats.
AB  - An amyloid-like isoform of a 33- to 34-kD glycoprotein, termed as the scrapie
      prion protein (PrPsc), plays a critical role in transmissible spongiform
      encephalopathies of animals and humans. It has even been suggested to present the
      responsible infectious agent. This protein is a posttranslationally modified form
      of the cellular isoform of prion protein (PrPc). Hitherto, little has been known
      about the functions of PrPc. In order to examine the localization of PrPc mRNA in
      rat tissues, the in situ hybridization technique was performed. In rat brain,
      PrPc mRNA was predominantly localized within pyramidal cells of the hippocampus,
      large neurons of the thalamus and neocortex, and Purkinje cells of the
      cerebellum. In the placenta, not only PrPc mRNA was localized to a subpopulation
      of decidual cells at the highest levels, it was also expressed in the amnion and
      mesodermal layer of the yolk sac. Furthermore, PrPc mRNA was also expressed in
      the myometrium of the uterus and seminiferous tubule in the testis. However,
      signals were not obtained in the lung, spleen, liver of prenatals and other fetus
      tissues. The distribution of rat PrPc mRNA portrayed the levels which were
      different among the various types of cells, suggesting that its expression may be
      regulated in a tissue-specific manner.

PMID- 8880381
TI  - Immunological responsiveness of Pekin ducks to core antigen of duck hepatitis B
      virus.
AB  - Cellular immune responses to the HBc or HBe antigen of hepatitis B viruses
      contribute to the pathogenesis of hepatitis B and to the elimination of the
      virus. Insufficient cytotoxic immune reactions against the core antigen may be
      one major reason for viral persistence in the absence of severe clinical
      symptoms. We attempted to stop viral persistence in the animal model of
      congenitally infected ducks by injection of recombinant DHBc particles, together
      with the strong immunostimulator Freund's adjuvant. However, the duck HBc antigen
      (DHBcAg)-treated ducks did not develop detectable liver disease, nor was the
      virus persistence affected. The congenitally infected ducks did not contain
      antibodies against DHBcAg before injection despite continuous production of duck
      hepatitis B virus, and developed only a weak transient antibody response after
      injection of recombinant DHBcAg together with Freund's adjuvant. Noninfected
      ducks developed, in contrast, a strong antibody response to the injected DHBcAg.
      We conclude that congenitally infected ducks are immunotolerant to DHBcAg and
      cannot be cured by immunotherapy with exogenous recombinant DHBcAg.

PMID- 8880382
TI  - Beta-interferon treatment of cervical intraepithelial neoplasia: a multicenter
      clinical trial.
AB  - Forty-nine women with cervical intraepithelial neoplasia (CIN) grade II were
      treated with systemic and/or local beta-interferon (beta-IFN) applications. The
      aim of the study was to compare the efficacy of different routes for the
      administration of beta-IFN, evaluate local and systemic beta-IFN tolerance, and
      determine whether disappearance of neoplastic lesions was related to the
      resolution of the concomitant human papillomavirus infection. The patients were
      randomized to receive intramuscular, intralesional or a combination of
      intramuscular and intralesional administration, or conventional treatment.
      Significant differences in the rate of lesion regression were observed between
      treated and untreated women. The highest frequency of complete response was
      observed with the therapy combining intramuscular and intralesional treatment.

PMID- 8880383
TI  - Growth inhibition of herpes simplex virus-type 1 in calphostin C-treated
      astrocytes.
AB  - The aim was to evaluate the effects of calphostin C (CC), a protein kinase C
      inhibitor, on lytic herpes simplex virus-type 1 infection of cultured rat
      astrocytes. At 24 h postinjection, the cell culture receiving CC treatment at 50
      nM concentration showed decreased cell detachment and retraction versus untreated
      infected controls; likewise, the infective virus yield was significantly lower in
      a dose-dependent manner. In contrast, image analysis failed to disclose
      differences in viral antigen immunolabeling at low drug concentrations thus
      suggesting that CC-induced inhibition of cytopathic effects and infectivity taken
      place through mechanisms not involving viral protein synthesis. Given the low
      dose required and the apparent lack of cytotoxic effects, present findings
      encourage additional studies on CC antiviral potential in the whole organism.

PMID- 8880384
TI  - Analysis of human papillomavirus type 16 E5 oncogene expression in vitro and from
      bicistronic messenger RNAs.
AB  - During a human papillomavirus infection (HPV), a set of spliced messenger RNAs
      (mRNA) are produced from the coding strand of the 8-kilobase virus DNA genome.
      These mRNAs have been isolated from cervical intraepithelial neoplasia biopsies,
      tumor biopsies and HPV type 16 (HPV-16)-containing cell lines, and subsequent
      analyses have shown that the different mRNAs are obtained by often complex
      splicing events. In the present study we have investigated the coding capacity of
      the HPV-16 E5 open reading frame (ORF) in an in vitro translation system and by
      the expression of a HPV-16 E5-CAT fusion gene from bicistronic messenger RNAs
      derived from polycistronic mRNAs which have previously been identified by others.
      Our results show that the HPV-16 E5 protein synthesis can only be initiated from
      the authentic ATG codon in the presence of E2 ORF translation. The E5 gene is
      found to be expressed only from a bicistronic mRNA with an E2 ORF upstream of the
      E5 gene indicating that the E5 protein is synthesized coordinated with the E2
      protein. The supposition that the E5 protein is synthesized early in infection is
      discussed.

PMID- 8880385
TI  - Escherichia coli expressed herpes simplex virus gG1 and gG2 proteins in ELISA and
      immunoblotting assays.
AB  - The type 1 and type 2 glycoprotein G (gG1 and gG2) of herpes simplex virus (HSV)
      were expressed in Escherichia coli as fusion proteins with the maltose binding
      protein (MBP) using the pMAL-c2 expression vector. The MBP-gG1 fusion protein
      contains all but the four amino acids from the amino-terminus of gG1, whereas the
      MBP-gG2 fusion protein was missing the first 30 amino acids that comprise the
      signal peptide of the protein. The diagnostic value of these antigens was
      examined by two methods: (1) immunoblot assay based on MBP-gG1 and MBP-gG2 fusion
      proteins present in crude E. coli cell extracts and (2) enzyme-linked
      immunosorbent assay (ELISA) of immunoaffinity-purified recombinant MBP-gG1 and
      MBP-gG2 fusion proteins. Of 28 serum samples known to have antibody to HSV-1 (10
      specimens positive for HSV-1 alone and 18 specimens positive for mixed antibody
      to HSV-1/HSV-2), 27 were reactive to the MBP-gG1 recombinant protein both in
      ELISA and in immunoblotting. In addition, of 20 serum samples known to have
      antibody to HSV-2 (2 specimens positive for HSV-2 alone and 18 samples positive
      for mixed antibody to HSV-1/HSV-2), 15 were found to be reactive to the MBP-gG2
      recombinant protein by ELISA and 16 by immunoblotting. None of the 13 HSV
      antibody-negative serum samples showed reactivity to the MBP-gG1 or MBP-gG2
      antigens by either assay. Moreover, none of the serum samples known to have
      antibody to HSV-1 alone showed reactivity to the MBP-gG2 recombinant antigen.
      This study verified the potential application of the E. coli-expressed
      recombinant gG1 and gG2 proteins as diagnostic antigens and demonstrated the MBP
      fusion system to be a simple and effective method of producing adequate amounts
      of low-cost, easily purified gG antigens.

PMID- 8880386
TI  - Use of continuous human lung cell culture for adenovirus isolation.
AB  - Adenovirus sensitivity, TCD50 value and mean time to cytopathic effect (CPE) were
      compared in Madin-Darby canine kidney (MDCK), rhesus monkey kidney (RhMK), human
      lung carcinoma (A549) and in newly identified continuous human lung (CHL) cell
      cultures. High-titer stock and positive original specimens were inoculated in
      culture. Patients specimens were also placed in shell-vial cultures. A549 and CHL
      cells demonstrated comparable sensitivity, however the former generally produced
      CPE earlier. Sensitivity was respectively reduced and poor in RhMK and MDCK
      cultures, as expected in cells of nonhuman origin. The performance of CHL for
      adenoviruses and other pathogens makes them a useful addition in diagnostic
      virology laboratories.

PMID- 8880387
TI  - Retroviral-mediated in vivo gene transfer into muscle cells and synthesis of
      human factor IX in mice.
AB  - Muscle cells, when transduced with a factor IX (FIX) expression vector, are
      capable of producing FIX protein and secreting it into the blood. These cells can
      thus serve as appropriate targets for gene transfer in hemophilia B patients. In
      this work, we studied the potential of retrovirus-mediated in vivo gene transfer
      of the FIX gene into muscle cells. Producer cells, which produce recombinant
      retroviruses containing the human FIX cDNA under the transcriptional control of
      the chicken beta-actin promoter, were treated with the cytostatic drug mitomycin
      C (MC), and injected into the rectus femoris muscle of 6-week-old CB-17/1cr
      severe combined immune-deficient (SCID) mice. As a control, SCID mice were
      injected with NIH 3T3 cells, which were stably transformed by the retroviral
      vector described above and therefore secreted FIX, but did not produce
      retroviruses. The injected MC-treated cells did not cause any tumours to develop
      in the mice, and the amount of human FIX in the plasma of mice injected with the
      producer cells was significantly higher, at any of the time points measured
      beyond 10 days postinjection, than the amount of human FIX in the plasma of mice
      injected with FIX-secreting 3T3 cells. These results indicate that muscle cells
      transduced by retroviruses produced human FIX and secreted it into the blood. In
      vivo gene transfer to muscle cells by injection of retrovirus-producing cells, or
      by direct injection of recombinant retroviruses, could prove to be important for
      the gene therapy of hemophilia B.

PMID- 8880388
TI  - New drug development for pediatric oncology.

PMID- 8880389
TI  - Pediatric drug development: a perspective from the Cancer Therapy Evaluation
      Program (CTEP) of the National Cancer Institute (NCI).
AB  - Well-designed and carefully conducted pediatric phase 1 trials are critical to
      the process of evaluating new agents for potential benefit in children with
      cancer, and the National Cancer Institute (NCI) has for a number of years
      sponsored pediatric phase I trials. The development of new agents for children
      with cancer differs in important ways from drug development for adults with
      cancer, primarily necessitated by the smaller number of children eligible for
      phase I trials in comparison to adults. Pediatric drug development is
      characterized by a greater need to prioritize new agents for evaluation, since
      many more agents can be evaluated in adults than can be evaluated in children.
      Pediatric phase I trials are also commonly conducted as multi-institutional
      collaborations, since most single institutions do not have enough eligible
      patients to complete phase I trials within a reasonable time. In addition,
      pediatric phase I trials begin at doses close to the adult maximum tolerated
      dose, thereby minimizing the number of patients required to complete pediatric
      phase I trials. While pediatric phase I trials have traditionally evaluated
      conventional cytotoxic agents, new classes of agents with distinctive mechanisms
      of action are entering clinical evaluation. These agents target specific cellular
      proteins (e.g., protein tyrosine kinases, protein kinase C isoforms, enzymes
      involved in controlling progression through the cell cycle). Determining whether
      these agents with specificity for critical cellular proteins will be effective
      anti-cancer agents will be an important objective of pediatric clinical
      investigations in the coming years.

PMID- 8880390
TI  - Phase I trials in paediatric oncology--the European perspective. The New Agents
      Group of the United Kingdom Childrens Cancer Study Group.
AB  - The current recommendations for Phase I trials should allow more confident
      interpretation of the toxicity and efficacy of new agents by providing a
      framework for multicentre and international co-operation. An overview of the aims
      and designs of Phase I trials is presented, along with a summary of current and
      recently published United Kingdom Childrens Cancer Study Group Phase I trials,
      and a discussion of some of the difficulties faced in the methodology and
      evaluation of Phase I studies in children.

PMID- 8880391
TI  - The importance of phase I/II trials in pediatric oncology.
AB  - Clinical trials in pediatric oncology over the past 30 years have led to the
      situation today where most children with newly diagnosed cancer can be treated
      effectively, and many are cured. Despite this dramatic improvement in outcome for
      many children diagnosed with cancer, about 30-40% of children will die of their
      disease [1]. Although some attempts have been made to improve outcome by
      increasing the dose intensity of existing therapies, intolerable side effects and
      marginal increases in cancer cell kill limit this approach. Clearly, effective
      new anti-cancer agents are necessary to significantly improve the survival and
      quality of life in children with cancer. Well-organized pediatric Phase I trials
      to establish the maximum tolerated dose (MTD), and Phase II trials to establish
      efficacy, are critical to the identification of new anti-cancer agents.

PMID- 8880392
TI  - Topoisomerase I interactive drugs in children with cancer.
AB  - Topotecan, irinotecan, and 9-aminocamptothecin (9-AC) are analogs of the plant
      alkaloid 20(S)-camptothecin (CMT), the prototypical DNA topoisomerase I
      interactive agent. These agents interact with the topoisomerase I-DNA complex and
      prevent resealing topoisomerase I-mediated DNA single-strand breaks. This
      eventual leads to double-strand DNA breaks and apoptosis or cell death.
      Topotecan, irinotecan, and 9-AC have shown significant activity in mice bearing
      pediatric solid tumor xenografts; the greatest antitumor responses were found
      with protracted continuous schedules. Preclinical data also suggest that
      maintenance of an exposure-duration threshold (EDT) may be required to achieve
      optimal cytotoxicity. Pediatric Phase I trials have evaluated the toxicity and
      safety to camptothecin analogs in children with relapsed solid tumors and
      relapsed acute leukemia. The primary dose-limiting toxicity (DLT) for the CMT
      analogs in children has been myelosuppression, except for mucositis observed with
      the 120-hr continuous topotecan infusion schedule. Pharmacodynamic relationships
      with these analogs have been reported between systemic exposure, and
      myelosuppression and mucositis. Although not a primary objective of the early
      Phase I studies, antitumor responses have been reported. In this review, the
      pharmacokinetic and pharmacodynamics of the CMT analogs studied in children are
      summarized, and future studies of these agents are discussed.

PMID- 8880393
TI  - New microtubular agents in pediatric oncology.
AB  - The taxanes are a new group of anticancer agents with a novel mechanism of
      action. They promote microtubule assembly and stabilize the microtubules.
      Paclitaxel (Taxol), the first agent in this group in clinical trials was isolated
      from the Pacific yew, Taxus brevifolia in 1971. Both in preclinical and clinical
      studies, paclitaxel and its semisynthetic analog docetaxel exhibit significant
      antitumor activity. This review will provide an overview of the clinical
      experience with the group of anti-microtubular agents, the taxanes in pediatric
      oncology.

PMID- 8880394
TI  - Multidrug resistance in pediatric oncology.
AB  - Cancer survival among children and adolescents has improved markedly due to
      evolution of multimodal treatment that incorporates combination chemotherapy,
      radiation therapy and/or surgery. However, 20-30% of children with malignancies
      will succumb to their disease or complications associated with their disease or
      treatment. A major limiting factor to improvement in survival among these
      patients is the occurrence of intrinsic and/or acquired resistance to our
      treatment interventions, chemotherapy and radiotherapy. Among these mechanisms,
      multidrug resistance, the focus of this review, is a well-documented phenomenon
      whose biochemistry, pharmacology and molecular biology has been extensively
      studied. A role for multidrug resistance in chemoresistance and therapeutic
      failure in childhood malignancies is suggested by the observation of clinical
      resistance to treatment regimes containing agents that are known substrates of
      multidrug resistance mechanisms. With the current results from studies in
      rhabdomyosarcoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, leukemia and
      retinoblastoma, the role of multidrug resistance is still unclear. Earlier
      studies attempted to define a role for P-glycoprotein-mediated multidrug
      resistance; however, a limited number of reports suggest that the multidrug
      associated resistance protein may play an active role in neuroblastoma. Further
      studies will be necessary using standardized and uniform approaches for the
      analyses of these mechanisms. Clinical trials directed toward reversal of
      multidrug resistance are premature since the exact role of P-glycoprotein is
      controversial in pediatric malignancies, the role of other mechanisms of
      multidrug resistance must be assessed and selective inhibitors of multidrug
      resistance have yet to be developed.

PMID- 8880395
TI  - Pharmacologic strategies for the treatment of meningeal malignancy.
AB  - There have been significant strides in the treatment and prevention of meningeal
      cancer, particularly meningeal leukemia, during the past thirty years. These
      advantages are a direct result of innovative therapeutic approaches specifically
      designed to overcome the limitations of systemically administered chemotherapy.
      Such approaches include the administration of intrathecal chemotherapy by
      intralumbar or intraventricular injection, the administration of very high-dose
      systemic chemotherapy, and the administration of cranial or craniospinal
      irradiation. A better understanding of the central nervous system
      pharmacokinetics of commonly used anticancer agents has also resulted in
      improvements in the treatment of meningeal cancer. In this article, the clinical
      pharmacology of the most commonly used intrathecal agents and pharmacologic
      strategies for the treatment of meningeal cancer will be discussed. In addition,
      an overview of new agents for intrathecal administration and other novel CNS
      targeted therapies will be presented.

PMID- 8880398
TI  - Nonfatal injuries in adolescents: United States, 1988.
AB  - PURPOSE: To describe the incidence and impact of nonfatal injuries in a national
      sample of adolescents. METHODS: Data were obtained from the 1988 Child Health
      Supplement of the National Health Interview Survey (NHIS). The NHIS is a
      continuous multistage probability sample of the civilian noninstitutionalized
      population of the United States. Adolescents 10-17 years old (N = 7,470) of the
      total number of 17,110 children under 18 years of age in the survey were studied.
      Incidence rates (I) were calculated for accidents, injuries, and poisonings
      (AIPs) requiring medical attention in the previous 12 months and recalled by the
      adult household interviewee. Information on sociodemographic factors and
      impairment were reported. Sample weights were used to derive population
      estimates. RESULTS: In 1988, 4,505,000 adolescents 10-17 years old were estimated
      to have experienced AIPs in the previous 12 months (I = 16.1/100), resulting in
      3.2 mean number days of bed rest, 4.1 mean number of days absent from school, and
      20% with limited activity due to AIPs. AIPs were most frequent in older
      adolescents 14-17 years of age (I = 18.2/100), males (I = 20.3/100), whites
      (19.5/100), and Midwest U.S. residents (I = 18.1/100). The most frequent AIPs
      were cuts (I = 59.6/1000), sprains (I = 51.3/1,000), and broken bones (I =
      43.1/1,000). AIPs most limiting to adolescents' activity were broken bones
      (62.6%), head injuries (58.3%), and sprains (55.7%). CONCLUSIONS: Although injury
      is the leading cause of death in adolescence, it also plays an important role in
      adolescent morbidity. Further national studies with better documentation of
      nonfatal injuries are needed to eliminate potential recall bias associated with
      an interview survey.

PMID- 8880396
TI  - Gene therapy in pediatric oncology.
AB  - An increased understanding of the molecular mechanisms of cancer and the ability
      to introduce exogenous genes into mammalian cells has led to the development of
      oncologic treatment strategies based upon gene transfer. Preclinical animal
      models have suggested a variety of approaches which are now being tested in
      pediatric trials. Studies using marker genes to trace cell origin have already
      generated important information regarding autologous bone marrow transplantation
      for pediatric cancers. A variety of therapeutic genes are also being clinically
      tested. Trials are underway to determine if introduction of immunostimulatory
      genes into cancer cells can be used to enhance host antitumor immunity. Treatment
      of primary brain tumors with insertion of drug sensitization genes is a promising
      new therapy that is also being clinically evaluated. Other strategies such as
      insertion of drug resistance genes into hematopoietic cells, anti-oncogene
      therapy, and tumor suppressor gene replacement are being tested in adults and may
      find use in pediatric cancer treatment. Although gene transfer offers promising
      new approaches for the therapy of pediatric cancer, many technical problems
      remain which limit efficacy and widespread use. Further basic research in the
      molecular biology of cancer and in vector development will be required to realize
      the full potential of gene therapy strategies.

PMID- 8880397
TI  - Folate, antifolates, and folate analogs in pediatric oncology.

PMID- 8880399
TI  - The development, reliability, and validity of a risk factor screening survey for
      urban minority junior high school students.
AB  - PURPOSE: To develop and evaluate a risk factor screening survey as a mechanism to
      identify inner-city junior high school students who may benefit from medical or
      mental health services available in school-based clinics. METHODS: A 36-item
      health risk factor screening survey was developed and administered to 3,787
      predominantly Hispanic students from four schools in an economically
      disadvantaged, medically underserved New York City school district. Students who
      indicated that they were experiencing one of five major risk factors
      (suicidality, sexual activity, parental or guardian substance use, personal
      substance use, or having run away) were scheduled to visit the clinic for
      services, and to have their survey responses validated by clinic interview.
      RESULTS: The development of the screening tool resulted in a short, easy to read
      and understand survey instrument that was feasible to administer within a
      classroom setting. The reliability of the instrument was excellent, and the
      results of the validity study indicated that it was successful in identifying
      students who did not need clinic services. The screening tool produced mixed
      results in identifying those truly in need through single item identification
      (e.g., produced a moderate number of "false positives"), although combining items
      on the screening tool produced much higher positive predictive values.
      CONCLUSIONS: This screening tool can be used to effectively focus limited
      clinical resources on those in need. Outreach surveys of this type should be
      considered as a valuable component of a school-based clinic service delivery
      strategy.

PMID- 8880400
TI  - Anticipatory guidance regarding sex: views of virginal female adolescents.
AB  - PURPOSE: To explore virginal female adolescents' perceptions of potential
      discussions with physicians regarding sexuality. METHODS: Twenty-seven virginal
      female adolescents from an urban high school completed a semistructured interview
      that explored perceptions of: (1) physicians as resources for discussions about
      sexuality; (2) content of potential sexuality discussions with physicians; and
      (3) risks and benefits of sexuality discussions with physicians. The relative
      emphasis of responses across the sample are described by mean proportional scores
      (MPS). RESULTS: Health care professionals were spontaneously identified by 33% of
      participants as potential resources for discussions about sexuality issues.
      Participants' perceptions of the potential content of sexuality discussions with
      physicians emphasized prevention of pregnancy and sexually transmitted infections
      (STIs) (MPS = .37), and physician counseling (MPS = .22). These topics included
      alternatives to sex and sex refusal skills. The perceived benefits of such
      discussions were gaining information or assistance regarding pregnancy and STI
      prevention (MPS = .32), talking with an expert (MPS = .19), and having a
      supportive relationship with a caring adult (MPS = .16). Lack of confidentiality
      was perceived as the major risk of adolescent-physician sexuality discussions
      (MPS = .29). CONCLUSION: Virginal female adolescents perceive a range of topics
      regarding sexuality as appropriate for discussions with physicians. This should
      be considered when providing anticipatory guidance counseling to virginal
      patients regarding sex. Concerns about confidentiality need to be addressed.

PMID- 8880401
TI  - Substance use: toward an understanding of its relation to nutrition-related
      attitudes and behavior among Israeli high school youth.
AB  - PURPOSE: To study the distribution, prevalence, determinants, and association
      between substance use (e.g., cigarettes, alcohol, and illegal drugs) and eating
      attitudes and behavior of high school students in the Negev region of Israel in
      order to provide an improved basis for prevention and health services. METHODS:
      An anonymous questionnaire regarding attitudes and behavior related to substance
      use and eating (e.g., breakfast before school, a snack or meal during school
      time, and three meals a day) was answered by 1,513 high school age youth.
      RESULTS: The study participants were at greater risk of poor eating behavior if
      they: (1) used cigarettes, alcohol, and/or illicit substances (p < .01); and (2)
      were female (p < .01). It was found that girls who used cigarettes were more
      likely than other young people studied not to eat properly and not to know about
      the relation between proper eating behavior and personal health (p < .05).
      Regardless whether cigarettes, alcohol, or illicit substances were used or not
      used, more than 50% of the youth reported not eating breakfast and 30% indicated
      they did not eat three meals daily. CONCLUSIONS: There are many concerns about
      the use and abuse of both licit and illicit substances among adolescents. More
      attention, however, needs to be given to the relationship between substance use
      and the attitudes and behavior of young people toward their health, including
      proper eating habits. The results support the need to develop drug prevention and
      health programs that are more comprehensive in terms of addressing the broad
      range of factors associated with adolescent growth and development.

PMID- 8880402
TI  - SAM memory: a link between past and future.

PMID- 8880403
TI  - "I believe in angels...".

PMID- 8880404
TI  - Effects of prenatal androgenization, melengestrol acetate, and Synovex-H on
      feedlot performance, carcass, and sensory traits of once-calved heifers.
AB  - Three studies were designed using a 2 x 2 factorial arrangement of treatments
      within each experiment to evaluate the effects of various management techniques
      on growth and carcass traits of once-calved heifers. In Exp. 1, 33 yearling (16
      control [C] and 17 prenatally androgenized [PA]) and 39 once-calved (20 C and 19
      PA) nonpregnant heifers were used to evaluate the effects of age and PA. Once
      calved heifers were approximately 31 kg heavier (P < .03) on-test, initially
      consumed 11% more (P < .01) DM, and gained 11% faster (P < .08), but had similar
      (P = .44) gain to feed ratios (.138 vs. .131) as yearlings. Growth performance
      was not affected by PA. The yearling and once-calved heifers were then
      slaughtered at approximately 707 and 1,080 d of age, respectively. Despite
      maturity differences (P < .01), marbling scores (P = .26) and percentage of
      choice carcasses (P = .27) were similar. However, on the basis of newly accepted
      grading changes, percentage of once-calved heifer carcasses grading choice
      decreased from 57.3 to 34.4%. Organoleptic properties did not differ. Experiments
      2 and 3 were then conducted to evaluate effects of commercially available
      products (melengestrol acetate [MGA] and Synovex-H) on feedlot characteristics of
      heifers following weaning of their first calf. In Exp. 2, 48 once-calved
      Simmental-based heifers were fed during the summer to a constant compositional
      fat thickness of .8 cm. Experiment 3 was conducted in the late fall and early
      winter, during which 52 moderately sized heifers were fed for 116 d postweaning
      and slaughtered. Performance of heifers in Exp. 2 was not affected by MGA.
      However, heifers fed MGA in Exp. 3 gained 9% faster (P < .05) than controls. In
      Exp. 2, Synovex-H tended to improve ADG (P < .09) and feed efficiency (P < .07),
      but did not affect performance in Exp. 3. Most carcass traits were not affected
      by either treatment. Nonpregnant, once-calved heifers seem to have a large
      capacity for efficient weight gain as compared with yearling heifers. However,
      hormonal compounds, such as testosterone propionate provided pre- or postnatally
      (Synovex-H), and MGA do not appear to provide the consistent, positive responses
      often seen with younger, more typical feedlot heifers.

PMID- 8880405
TI  - Effects of selection for scrotal circumference in Limousin bulls on reproductive
      and growth traits of progeny.
AB  - Nine pairs of Limousin bulls from nine contemporary groups were acquired, with
      each pair consisting of one large scrotal circumference (SC) bull and one small
      SC bull. Average adjusted yearling scrotal circumferences were 36.3 cm (SD 1.6
      cm) and 28.5 cm (SD .9 cm) for large SC (LP) and small SC (SP) bulls,
      respectively. In addition to the phenotypic grouping, non-parent SC EPD were used
      to group bulls into high (HE, > .53 cm), average (AE), and low (LE, < -.61 cm)
      lines. Each bull was mated to a randomly assigned group of 15 to 20 Brangus x
      Hereford cows each yr for 1 to 3 yr. Birth weights, weaning and yearling weights
      and heights, and ultrasound measurements for backfat and ribeye measurements were
      taken on 407 progeny. Blood samples were collected on 210 heifer progeny when
      they averaged 11, 13, and 15 mo of age to determine whether they had reached
      puberty. When subjected to a breeding soundness exam (BSE), LP bulls scored
      higher (P < .01) for motility as well as total BSE score. The LP calves had
      heavier birth weights (P < .05) and greater testicular mass at weaning (P < .01)
      than SP calves. The HE and AE bull calves had greater (P < .02) testicular mass
      than did the LE bull calves. A greater (P < .05) percentage of HE heifers had
      reached puberty by the 11- and 13-mo measurements than either the AE or LE
      heifers. The HE heifers reached puberty at a younger age than AE (P < .01) or LE
      (P < .001) heifers. Selection using SC EPD was more effective than phenotypic
      selection in reducing age at puberty in daughters.

PMID- 8880406
TI  - Milk production in Angus, Brahman, and reciprocal-cross cows grazing common
      bermuda grass or endophyte-infected tall fescue.
AB  - Milk yield and quality were measured on 139 Angus, Brahman, and reciprocal-cross
      cows grazing common bermuda grass or endophyte-infected tall fescue for 4 yr to
      evaluate interactions of direct and maternal breed effects and heterosis for
      these traits with forage environment. Milk yield was estimated by method of
      milking machine, and milk fat, protein, and somatic cell counts were evaluated in
      a commercial dairy laboratory. Monthly estimates were made beginning on an
      average d 61 of lactation and continued monthly for six estimates in 3 yr and
      five estimates in 1 yr. Data were averaged over month within year, and the model
      included sire breed, sire in sire breed, dam breed, forage, and age averages.
      Somatic cell counts were transformed using natural logarithms prior to analyses.
      Forage effects for milk yield were dissimilar among sire breed x dam breed
      subclasses (P < .10), resulting in higher levels of heterosis on common bermuda
      grass than on tall fescue. Maternal breed effects for milk yield favored Angus on
      bermuda grass (P < .05) but not on tall fescue, whereas direct breed effects were
      similar on both forages and favored Brahman. Milk fat was reduced on tall fescue
      compared to bermuda grass by an average of .6% (P < .01), and direct breed
      effects were similar across forages and averaged 1.04% (P < .01) in favor of
      Brahman. Heterosis and maternal breed effects for milk fat were not important.
      There was little evidence of direct and maternal breed effects or heterosis for
      milk protein or somatic cell counts. These data suggest that heterosis for milk
      yield is larger on common bermuda grass than on tall fescue and that grazing
      endophyte-infected tall fescue is detrimental to milk fat.

PMID- 8880407
TI  - Effects of the level of asphyxia during delivery on viability at birth and early
      postnatal vitality of newborn pigs.
AB  - Newborn pigs (n = 117) were used to provide information on the relationships of
      degree of asphyxia during delivery, viability at birth, and some striking aspects
      of postnatal vitality including survival, interval between birth and first udder
      contact and between birth and first suckling, rectal temperature at 24 h of life
      (RT24), and growth rate over the first 10 d of life. The degree of asphyxia at
      birth was estimated from cord blood pCO2, pH, and lactate levels. Onset of
      respiration, heart rate, skin color, and attempts to stand during the first
      minute after birth were used to estimate the viability score. Neonatal asphyxia,
      i.e., decreased blood pH and increased blood pCO2 and lactate, was associated
      with the production of unusually high levels of catecholamines. The degree of
      asphyxia increased with late position in the birth order (P < .01) and was higher
      in piglets born posteriorly (P < 0.5). Further, the average blood pCO2 within a
      litter increased (P < .05) with litter size. The was an inverse relationship
      between the degree of asphyxia and the viability score (P < .001). Highly viable
      piglets reached the udder more rapidly (P < .001) and had a higher RT24 (P <
      .001) than those of low viability. Plasma glucose concentrations increased with
      blood pCO2 and plasma epinephrine concentrations (P < .001). Neonatal asphyxia
      reduced postnatal vitality by delaying the first contact with the udder (P < .03)
      and was associated with a lower RT24 (P < .05), growth rate (P < .001), and
      survival over 10 d (P < 0.06). These variables, i.e., interval between birth and
      first udder contact, RT24, and growth rate, were correlated with birth weight (P
      < .001); RT24 was also shown to decrease (P < .001) with the time taken to reach
      the udder. Overall, results suggest that piglet suffering from asphyxia during
      delivery are less viable at birth and less prone to adapt to extrauterine life.

PMID- 8880408
TI  - Effect of prostaglandin F2 alpha administered before estrus synchronization with
      norgestomet and estradiol valerate on calving rates of beef cows.
AB  - Three experiments were conducted to evaluate the effects of prostaglandin F2
      alpha treatments 5, 9, and 14 d before Syncro-Mate B on calving rates of 1,072
      beef cows from inseminations at a pre-set time. The administration of
      prostaglandin F2 alpha 5 d before Syncro-Mate B decreased (P < .01) calving
      rates. This reduction was associated with lower (P < .05) calving rates in cows
      administered Syncro-Mate B in the first half of the estrous cycle. Calving rates
      were unaffected n cows administered prostaglandin F2 alpha 9 d before Syncro-Mate
      B. The administration of prostaglandin F2 alpha 14 d before Syncro-Mate B reduced
      (P < .05) calving rates in previously anestrous cows. In summary, prostaglandin
      F2 alpha should not be administered to postpartum cows 5 to 14 d before Syncro
      Mate B synchronization.

PMID- 8880409
TI  - Health, welfare, and productivity of pigs housed under Specific-Stress-Free
      conditions in comparison with two-site systems.
AB  - This study describes the effects of housing pigs under optimal climatic
      conditions in a Specific-Stress-Free (SSF) housing system on health, behavior,
      immunological responsiveness, and production performance of 78 pigs from 10
      litters. Pigs housed in an SSF system, where they were neither mixed nor
      transported, were compared with a control group of pigs for which transport was
      simulated and which were mixed at approximately 25 kg; transportation to another
      location and mixing are usual procedures in two-site systems. The SSF pigs had a
      higher growth rate for the finishing period (P < .01), but this was a smaller
      improvement in performance than in previous studies, probably due to less mixing
      in this study. Clinical signs were hardly seen in the SSF group, but aggression
      after mixing caused ear lesions in the control group. Pigs that were not mixed
      had a higher response 12 and 18 h after an intradermal injection of
      phytohemagglutinin (P < .001) compared to the control pigs. At 1 d ad 1 mo after
      mixing the control pigs, more agonistic interactions were seen in these pigs
      compared with the SSF pigs (P < .05 and P < .01, respectively). In conclusion,
      health, welfare, and production performance of pigs are improved when pigs are
      kept in an SSF housing system where they are not mixed or transported.

PMID- 8880411
TI  - Incidence and sensory evaluation of injection-site lesions in beef top sirloin
      butts.
AB  - The effects of ongoing quality assurance initiatives on the national incidence of
      injection-site lesions and the impact of these lesions on the sensory
      characteristics of top sirloin butts were examined by a series of audits and two
      experiments. The national incidence of injection-site lesions in top sirloin
      butts (n = 98,192) has not changed between July 1993 (10.91%) and July 1995
      (10.19%). However, during this same period, the mean weight of injection-site
      lesion trim increased (P < .05) from 102.63 +/- 12.56 g to 152.81 +/- 13.24 g.
      Eighty percent of lesions examined during this period were classified as
      chronologically "older," originating from injections given either during
      preweaning, stocking, or in the early feeding period; however, there was an
      increase (P < .01) in the incidence of nodular scars during the audit period,
      likely created by intramuscular injections during the mid- to late-feeding
      periods. Warner-Bratzler shear measurements of lesion-afflicted steaks taken near
      the site of lesions and in areas up to 7.62 cm from the lesion center were
      significantly greater than similar measurements on control top sirloin steaks.
      Panelist tenderness scores for mildly lesioned steaks were lower (P < .05) and
      had greater within-(P < .01) and among- (P < .05) steak variation than control
      (normal) steaks. Mean juiciness ratings were higher (P < .001) for lesioned
      steaks; however, steak flavor intensity variation was greater within injection
      site lesioned vs control top sirloin steaks, with undesirable flavors reported by
      panelists. Injection-site lesions still occur at an unacceptable frequency in the
      top sirloin butt, and those lesions, if not removed entirely, can dramatically
      reduce the desirability of top sirloin steaks.

PMID- 8880410
TI  - The effect of dietary fat inclusion on growth, carcass characteristics, and
      chemical composition of rabbits.
AB  - Two hundred ten Californian x New Zealand White rabbits were used to study the
      influence of diet and slaughter weight (2.0, 2.25, and 2.5 kg) on feed intake,
      growth, feed efficiency, carcass characteristics, and body chemical composition.
      Seven diets were formulated to contain 24% ADF: Diet C (control) had no added
      fat; Diets T, O, and S contained 3% of added beef tallow, oleins, and soybean
      oil, respectively; Diets TWS, OWS, and SWS contained the same level and types of
      fat plus 18% heated whole soybeans (WS) to increase the dietary fat by 3%. Fat
      addition did not affect ADG or dressing percentage, but it improved feed:gain
      ratio (.06 for each 1% of dietary fat, P < .001). Although the main measurements
      of carcass were not influenced by fat addition, the rabbits fed diets containing
      the highest fat percentage had the highest weights of perirenal (P < .001) and
      scapular (P < .01) depots and the highest body fat content (P < .01). The
      increase in slaughter weight improved all the desirable carcass characteristics
      measured but imparied feed:gain (by 13%, P < .001). Increasing slaughter weight
      also increased the perirenal and scapular fat depots by 40 an 24%, respectively
      (P < .001)< and the body fat content by 28% (P < .01). There were no differences
      in the utilization of animal and vegetable fats, and only for some traits ADG,
      feed intake, kidney weights) did the diets with soybean oil result in better
      responses than those with oleins. The results indicate that fat addition to
      fibrous diets extends the rabbit's growing period without impairing the feed:gain
      ratio. The joints of rabbits killed at heavier weights have more desirable
      weights for marketing the carcass on a retail cut basis.

PMID- 8880412
TI  - Overexpression of beta-subunit of thyroid-stimulating hormone in Meishan swine
      identified by differential display.
AB  - Anterior pituitary gland RNA isolated from Meishan (MS) and White Composite (WC)
      sexually mature boars was compared by a newly developed method of differential
      expression cloning called differential display. A number of cDNAs were identified
      that differed distinctly in expression between these breeds. The gene for beta
      subunit of thyroid-stimulating hormone (TSH-beta) was initially identified as
      more highly expressed in MS than in WC boars. Subsequently, RNase protection
      assays and TSH RIA were used to quantify the magnitude of differences in
      transcription and translation in both males and females. Mature MS pigs had
      threefold greater expression of TSH-beta (P < .05) and greater plasma TSH
      concentrations than mature WC pigs (P < .01). The cDNA cloning and sequence
      analyses indicate identity in TSH-beta mRNA between MS and WC males. Elevated
      plasma TSH concentration may contribute MS pigs reaching sexual maturity earlier
      than WC or other European breeds. The method used in this study provides a useful
      molecular tool 1) to detect differentially expressed genes, 2) to study genetic
      variation that occurs at the transcription level between individuals,
      populations, or breeds; and additionally, 3) to identify candidate genes that
      control economically important quantitative traits in livestock.

PMID- 8880413
TI  - Genetic parameters for growth and carcass traits in Japanese brown cattle
      estimated from field records.
AB  - Field records from 14,380 Japanese Brown steers by 92 sires were used to estimate
      genetic parameters for growth and carcass traits. Multipletrait restricted
      maximum likelihood (REML) procedures accounting for relationships among sires
      were used in estimating (co)variance components among average daily gain during
      fattening periods (ADG), carcass weight (CWT), longissimus muscle area (LMA), rib
      thickness (RT), marbling score (MS), and subcutaneous fat thickness (SFT).
      Heritability estimates on an age-constant basis were .22, .37, .38, .26, .40, and
      .35 for ADG, CWT, LMA, RT, MS, and SFT, respectively. Estimated genetic
      correlations (rg) among ADG, CWT, and RT were positive and moderately high (.48
      to .85). The rg between MS and SFT was -.12.

PMID- 8880414
TI  - The influence of extracellular matrix substrata on preadipocyte development in
      serum-free cultures of stromal-vascular cells.
AB  - The influence of the extracellular matrix (ECM) and ECM components on
      preadipocyte development was examined in primary cultures of adipose tissue
      stromal-vascular (S-V) cells. Extracellular matrix derived from Engelbreth-Holm
      Swarm (EHS) cells or tumors enhanced several aspects of adipogenesis in vitro. In
      comparison to uncoated and fibronectin substrata, EHS-ECM substratum markedly
      increased attachment, spreading, and hypertrophy of preadipocytes while
      antagonizing spreading of non-preadipocytes. In addition, adipocyte number
      increased (P < .05) on these substrata despite no increase in total cell number:
      this resulted in a greater (P < .05) proportion of preadipocytes. These effects
      of EHS-ECM were also observed with laminin substrata per se, whereas types I and
      IV collagen and fibronectin had no influence. In contrast to all other substrata,
      adipocyte number decreased and total cell number increased 2.5-fold on ECM
      derived from corneal endothelial cells; this resulted in the lowest proportion of
      preadipocytes. Challenging cultures with adipogenic media (+serum) did not
      counter the inhibitory influence of corneal endothelial ECM, whereas
      dexamethasone partially neutralized the inhibitory influence of this ECM. These
      studies clearly show that source or type of the ECM dictated the influence of ECM
      substrata on preadipocyte development in primary S-V cultures. However, these
      studies indicated that the ECM and in particular laminin may play a critical role
      in morphological aspects of preadipocyte development.

PMID- 8880416
TI  - Evaluation of growth curves of Brahman cattle of various frame sizes.
AB  - Partial stage and complete life-cycle growth curves of Brahman cattle were
      obtained for small, medium, and large frame sizes for a herd under grazing
      conditions in a subtropical environment. Data were grouped into three stages:
      birth to weaning (stage 1), weaning to 20 mo (males) or 32 mo (females) of age
      (stage 2), and 32 mo of age to maturity (females only; stage 3). Within each
      stage, multiplicative growth models were developed for each frame size and sex.
      Body weight growth on age t was represented as exp(a + bt + ct2) for stages 1 and
      2, and as exp(A + B exp(kt)) for stage 3. The effects of sire and progeny within
      sire were considered in all models. For stages 2 and 3, the effect of season was
      also included. To obtain complete life-cycle curves, a growth stage
      multiplicative model with stages 1 and 2 was defined; stage 3 was also included
      for females. Due to a 1-mo adaptation period after weaning, a transition stage
      between stages 1 and 2 was defined and represented by the model exp(a + bt). In
      stage 1, the shape of the growth curve differed (P < .05) among frame size
      groups; sex did not affect the shape of the growth curves, but bull calves had
      heavier (P < .05) weights than heifer calves. In stage 2, the shape of the growth
      curves did not differ among frame sizes, but BW differed among frame sizes (P <
      .05) and sex affected (P < .05) the shape of the growth curves. In stage 3, the
      shape of the growth curves differed (P < .05) among frame sizes. There were sire
      effects (P < .05) for stages 1 and 2, but sire effects were not significant for
      stage 3. Season effects were important (P < .05) for stages 1 and 2. These
      results suggest that variability in growth patterns provides an opportunity to
      use management and nutrition to improve production efficiency in cattle of
      different frame sizes.

PMID- 8880415
TI  - Effect of protein and protein-free energy intake on protein and fat deposition
      rates in preruminant calves of 80 to 240 kg live weight.
AB  - Two experiments were conducted to quantify the effects of protein intake on
      protein and fat deposition rates at two protein-free, energy intake levels in 90
      preruminant Holstein Friesian x Dutch Friesian calves. The two experiments were
      similar in design, but were performed in two different weight ranges: 80 to 160
      kg BW and 160 to 240 kg BW in Exp. 1 and 2, respectively. In each experiment,
      calves were allocated to either an initial slaughter group or to one of 12
      treatments (three calves per treatment), which consisted of six protein intake
      levels at each of two protein-free energy intake levels. Calves were slaughtered
      and analyzed for body composition when they had reached the target weight. A
      balance study was conducted when calves reached 120 and 200 kg BW in Exp. 1 and
      2, respectively. Protein digestibility increased with increasing protein intake
      in both experiments (P < .001). Average daily gain of the empty body varied
      between 640 and 1,340 g/d and between 420 and 1,370 g/d in Exp. 1 and 2,
      respectively, and was affected by protein (P < .001) and protein-free energy
      intake (P < .001). The calves responded to increased protein intake by increasing
      their protein (P < .001) and fat (P < .01) deposition rates. Maximum protein
      deposition was reached in the second experiment at 244 g/d. Extra protein-free
      energy intake resulted mainly in extra fat deposition (P < .001), but also
      increased the protein deposition (P < .01), even at low protein intake levels. In
      both experiments, the response of protein deposition rate to increased protein
      intakes was low: about 30% of the extra ingested protein was deposited. These
      results clearly demonstrate a low priority for partitioning dietary protein into
      protein gain in these calves.

PMID- 8880417
TI  - Effect of selection for lifetime production of lamb weaned on hormonal factors
      that affect growth in Targhee ewes and lambs.
AB  - Targhee ewes (n = 22, average age 5 yr) rearing twin lambs were used to
      investigate serum growth hormone (GH), IGF-I, triiodothyronine (T3), thyroxine
      (T4), and prolactin (PRL; ewes only) concentrations associated with selection
      pressure for lifetime production of kilograms of lamb weaned per ewe. Period 1
      started on d 4 after birth and was conducted in confinement. Periods 2, 3, and 4
      were conducted on fenced intermountain sagebrush-bunchgrass range starting at an
      average of 49, 84, and 112 d after birth, respectively. Blood samples were
      collected hourly for 6 h on d 4, 11, 18, 25, 49, 84, and 112 after lambing. Ewe
      models included the fixed effect for line, with ewe age, lambing date, and
      starting weight nested within line as potential covariables. Lamb models included
      fixed effects for line, sex, and sibling sex, with lamb age and birth weight
      nested within line tested as possible covariables. Growth hormone concentrations
      were greater (P = .06) for selected than for control ewes, but lamb GH
      concentrations did not differ (P = .90) between selected and control lambs. Ewe
      prolactin concentration tended (P = .13) to be greater for control than selected
      ewes. Ewe and lamb IGF-I did not differ (P > .55) between selected and control
      ewes and lambs. Ewe T3 and T4 concentrations did not differ (P > .19) between
      selected and control ewes; however, lamb T3 and T4 concentrations were greater (P
      < .01) for control than for selected lambs. Increased GH concentration in
      selected ewes seemed to be associated with greater milk production. Differences
      in selected and control lamb T3 and T4 concentrations could be an indicator of
      receptor sensitivity, metabolic activity, or seasonal reproductive transitions in
      ewe lambs.

PMID- 8880418
TI  - The effect of postruminal amino acid flow on muscle cell proliferation and
      protein turnover.
AB  - An experiment was conducted to characterize the effects of postruminal
      administration of casein, glutamine, cornstarch, and water on protein turnover
      and in vitro muscle cell proliferation. Four MARC III steers (205 kg) were fed a
      protein-restricted bromegrass hay-based diet (2.86 Mcal of DE/kg and 13.6 g of
      N/kg). Using a 4 x 5 Latin square arrangement balanced for residual effects,
      casein and glutamine, equal to 50% of basal dietary nitrogen intake, cornstarch,
      isocaloric with casein infusion, or an equal volume of water was continuously
      infused into the abomasum of steers. Blood samples, collected every 2 h for 24 h
      after 7 d of infusion, were tested for the effect on cell cycle kinetics and
      myotube protein turnover. Urine and feces were also collected for 4 d after blood
      sampling for nitrogen balance and fractional skeletal muscle degradation. The
      mitogenic activity and ability of serum to influence rate of myoblast
      proliferation in a dose-dependent manner was influenced (P < .05) by infusate:
      casein > cornstarch > glutamine = water. Abomasal infusion of casein and
      cornstarch increased (P < .05) in vitro muscle protein synthesis and decreased (P
      < .05) in vitro muscle protein degradation, whereas abomasal glutamine infusion
      only increased (P < .05) in vitro muscle protein synthesis. Abomasal glutamine
      infusion decreased (P < .05) fractional skeletal muscle protein degradation and
      synthesis; however, fractional muscle protein accretion tended to increase due to
      a greater decline in fractional muscle protein degradation. In contrast, abomasal
      casein infusion increased (P < .05) fractional skeletal muscle protein synthesis,
      breakdown, and accretion. These results suggest that muscle hypertrophy may be
      regulated by serum constituents whose activity is affected by postruminal amino
      acid flow.

PMID- 8880419
TI  - Breed differences in boar taint: relationship between tissue levels boar taint
      compounds and sensory analysis of taint.
AB  - A total of 228 intact male pigs form Duroc, Hampshire, Landrace, and Yorkshire
      breeds were used in the experiment. Samples of salivary gland and backfat were
      collected at slaughter for colorimetric assay of salivary and fat 16-androstene
      levels and fat skatole levels. Fat levels also were tested by a sensory panel
      using an R-index technique for detecting the presence of boar taint. The
      proportion of tainted carcasses determined by the sensory panel was 5.0% for
      androstenone and 11.4% for skatole, with a combined total of 15.0% tainted from
      either source. Sensory analysis of taint showed a lower proportion (P < .05) of
      tainted carcasses in Hampshire, with no difference in taint across the other
      three breeds. Analysis of taint compounds indicated that overall 14.5% of pigs
      had salivary gland 16-androstene levels and 20.9% had fat 16-androstene levels
      above acceptable limits. There was a higher (P < .05) proportion of Duroc pigs
      above the threshold levels for 16-androstenes in both salivary gland and fat.
      Landrace pigs had the lowest (P < .05) average tissue concentrations of steroids
      and skatole. Across breeds, only 1.8% of pigs had fat skatole concentrations
      above .25 ppm, which has been suggested as threshold levels of skatole for taint.
      The canonical correlation coefficient between fat compound levels and the R
      indices of fat 16-androstenes and skatole was .40 (P < .001). Our results
      indicate breed differences in tissue levels of taint compounds and in taint
      assessed by a sensory panel. Levels of 16-androstene steroids were highly
      associated with taint, but more pigs had measured levels above the threshold than
      those identified as tainted by sensory analysis. Levels of fat skatole were low
      overall and did not account for all the pigs judged as tainted from skatole by
      sensory analysis.

PMID- 8880420
TI  - Growth, carcass, and tenderness characteristics of virgin, spayed, and single
      calf heifers.
AB  - Fifty-three Angus/Gelbvieh rotationally crossed heifers were slaughtered after
      100 d on a high-concentrate diet. The average slaughter age for each of three
      different groups was 31, 33, or 35 mo, which falls within the USDA's 30- to 42-mo
      age range for animals producing "B" maturity carcasses. Each age group consisted
      of five or six heifers that had never been bred (virgin), six heifers
      ovariectomized at 1 yr of age (spayed), and six heifers that had weaned calves
      approximately 120 d postpartum (single-calf). Slaughter weight was higher (P <
      .05) for the virgin heifers but total weight gain in the feedlot was similar
      among the three groups. Single-calf heifers fed 100 d after weaning calves tended
      to be fatter than virgin or spayed heifers. Carcass maturity scores for the
      single-calf, virgin, and spayed heifers were different (P < .05); single-calf
      heifers produced carcasses that appeared older and spayed heifers produced
      carcasses that appeared younger. Maturity scores coupled with lighter and shorter
      metacarpal bone weights indicated single-calf heifers matured earlier (P < .05)
      than the other groups. Panel tenderness and Warner-Bratzler (WB) shear values of
      rib roasts from virgin, spayed, and single-calf heifers were determined. No
      differences among groups of heifers existed but scores within each group varied
      greatly. Marbling score was correlated (P < .05) with panel tenderness and shear
      force and the hydroxylysylpyridinium (HP) crosslink of muscle collagen was
      correlated (P < .05) with shear values. Because no significant (P < .05)
      correlation existed between HP in bone collagen or HP or WB shear values in
      muscle, we concluded that collagen maturation processes in muscle and bone occur
      independently. With the exception of differences in bone maturity scores, few
      meaningful differences in characteristics of virgin, spayed, and single-calf
      heifers existed, but these maturity differences could change carcass grade and
      influence value.

PMID- 8880421
TI  - Influence of realimentation of mature cows on maturity, color, collagen
      solubility, and sensory characteristics.
AB  - Cull beef cows (n = 80) that had consumed similar grassland diets were assigned
      to one of four feeding periods (0, 28, 56, and 84 d) and subdivided into two
      groups fed either a high-energy, high-protein diet or a high-energy, low-protein
      diet. Treatments were designed to examine the effect of time on feed, dietary
      protein, and electrical stimulation on carcass traits, composition, shear force,
      sensory profile, collagen characteristics, and myoglobin state. Within 1 h of
      slaughter, the right side of each carcass was electrically stimulated, and the
      left side served as the control. The only trait influenced by protein level was
      longissimus muscle area, for which a high-protein diet resulted in larger (P <
      .05) longissimus muscle areas. Increased time on a high-energy diet increased
      USDA yield grade and sensory ratings; however, metmyoglobin and reduced myoglobin
      values decreased between 0 and 28 d on feed. Electrical stimulation improved lean
      color, shear force values, and sensory attributes. Electrical stimulation
      decreased shear force by 2.8 kg for 0-d carcasses. With subsequent days on feed,
      shear force values continued to decrease, but this effect was minimal in
      electrically stimulated carcasses. However, protein level did not significantly
      influence palatability and quality attributes. The greatest (P < .05) improvement
      in marbling score was observed in electrically stimulated carcasses from cows fed
      for 84 d. Additionally, feeding a high-protein diet for 84 d resulted in a
      slightly lower maturity score. Even though values for palatability and quality
      traits were improved by antemortem and postmortem treatments, the magnitude of
      improvement may not be great enough for steaks from mature fed cows to be
      considered as acceptable as steaks from young fed beef.

PMID- 8880422
TI  - Effect of supplemental pig milk replacer on litter performance: seasonal
      variation in response.
AB  - The objective of this study was to determine the effect of supplemental milk
      replacer on sow and litter performance. The study was conducted in 12 farrowing
      groups (171 litters) over a 3.5-yr period (October 1990 to April 1994).
      Commercial milk replacer was prepared fresh daily (150 g/L) and offered with ad
      libitum access in the farrowing crates within 24 h of parturition and was
      continued through weaning (d 21). Average pig weight (control, 5.5 kg/pig;
      supplemented, 6.4 kg/pig; P < .001) and total litter weight (control, 52.2
      kg/litter; supplemented, 60.9 kg/litter; P < .001) at weaning were greater for
      litters receiving supplemental milk replacer. There was no effect (P > .2) of
      supplemental milk replacer on feed intake, backfat thickness, or body weight loss
      in the sow. Consumption of milk replacer varied greatly among litters. A portion
      of this variation in intake was accounted for by differences in ambient
      temperature among farrowing groups. Average milk replacer intakes (liters per
      pig) from birth to d 21 were 2.5 L/pig (.375 kg dry matter) and 9.9 L/pig (1.49
      kg dry matter) for pigs born during the cool and warm seasons, respectively (P <
      .001). The weaning weight advantage conferred by milk replacer was most evident
      during the warmer months. Sow feed intakes averaged 5.8 and 3.9 kg/d over the
      same periods (P < .001). These results demonstrate the advantage of milk replacer
      on weaning weight and indicate that the greatest benefit from the supplement is
      during the warmer months when sow feed intake and subsequent milk production are
      lower.

PMID- 8880424
TI  - Reconstitution of body reserves in multiparous sows during pregnancy: effect of
      energy intake during pregnancy and mobilization during the previous lactation.
AB  - Multiparous Large White sows were used in two experiments to determine the
      effects of energy intake on the reconstitution of body reserves during pregnancy.
      In Exp. 1, 21 sows received one of three different energy levels during
      pregnancy: 7.4, 8.8, or 10.4 Mcal DE/d. In Exp. 2, two energy levels (7.9 and 9.2
      Mcal DE/d) were fed to 36 sows that mobilized low or high amounts of body
      reserves during the previous lactation (6 or 12 pigs per litter, respectively).
      Nitrogen balances were conducted during five 7-d periods at 11, 32, 53, 82, and
      104 d of gestation. All the experimental sows were slaughtered and dissected at
      the end of pregnancy; 24 control sows were similarly slaughtered at mating in
      order to estimate composition of BW gain, according to the comparative slaughter
      technique. In the two experiments, average nitrogen (N) retention increased
      linearly with energy supply from 9.9 to 14.5 g/d in Exp. 1 (P < .001) and from
      10.2 to 12.5 g/d in Exp. 2 (P < .05). Nitrogen retention was not affected by the
      extent of mobilization of body reserves during the previous lactation in Exp. 2.
      In both experiments, carcass weight (P < .001), muscle weight (P < .01), and
      dissectable fat weight (P < .001, Exp. 1; P < .01, Exp. 2) increased with energy
      supply. We conclude that in high-producing modern multiparous sows, energy supply
      during gestation is a limiting factor for N retention and muscle weight gain and
      should be approximately 8,500 kcal DE/d to ensure adequate restoration of body
      reserves.

PMID- 8880423
TI  - Ontogeny and dietary modulation of 3-hydroxy-3-methylglutaryl-CoA reductase
      activities in neonatal pigs.
AB  - The development of hepatic and ileal -hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase was studied in three types of young pigs crossbred, obese, and
      lean pigs). Pigs were fed one of two diets: a high-fat (coconut oil), high
      cholesterol 1.0%; designated HC) diet or a high-fat, noncholesterol (designated
      NC) diet from postpartum d 3 to d 13, 25, and 42 (crossbred only). There were
      four pigs per age per diet group (except for obese pigs). Liver and ileal mucosal
      microsomal reductase activities were determined by the conversion of [14C]HMG-CoA
      to mevalonic acid followed by lactonization of the product. The samples were
      analyzed by thin layer chromatography and liquid scintillation spectrometry.
      Hepatic reductase activity (1 unit of specific activity = 1 pmol.min-1.mg protein
      1) was < 20 units on d 3 in all groups. By d 13, the activity was 40 to 46 units
      in all groups of pigs fed HC and approximately 50 to 80 units in pigs fed NC.
      Reductase activity then decreased at d 25 to 18 to 40 units in pigs fed NC and to
      < 14 units in pigs fed HC. The d 42 reductase values (crossbred only) were
      approximately 14 units for pigs fed both HC and NC diets. Intestinal reductase
      activity was not affected (P > .1) by either age or diet. The data suggest that
      dietary cholesterol suppressed hepatic reductase activity in young pigs (d 13 and
      25) from divergent genetic backgrounds. The data also suggest that the stage of
      development is a dominant factor in regulating porcine hepatic HMG-CoA reductase
      activity, which was considerably increased at d 13, even in pigs fed HC diets.
      The relatively modest increase in plasma cholesterol, even in pigs fed
      cholesterol during the suckling period, provides evidence that both dietary and
      endogenously synthesized cholesterol are probably used predominantly for tissue
      building in very young pigs (d 13).

PMID- 8880425
TI  - Energy metabolism in relation to physical activity in growing pigs as affected by
      type of dietary carbohydrate.
AB  - The effect of dietary carbohydrate source on physical activity in relation to
      metabolic rate in pigs was studied. Six groups of 12 pigs (50-kg, castrated
      males) were fed one of two diets: a starch diet or a non-starch polysaccharide
      (NSP) diet. Both diets had a similar calculated net energy content. The starch
      diet contained 13% tapioca, and the NSP diet contained 17% sugar beet pulp
      silage. Pigs were housed in groups and fed at approximately two times maintenance
      (approximately 900 kJ ME.kg-.75.d-1). Nitrogen and energy balances were measured
      per group during a 7-d experimental period, which was preceded by a 2-wk
      adaptation period. Heat production and physical activity were measured during
      successive discrete 9-min intervals. Metabolizability of gross energy was 79.4%
      and 78.2% for the starch-fed and NSP-fed pigs, respectively (P < .10). Activity
      differed between treatments. Activity-related heat production tended to be higher
      for the starch-fed pigs than for those fed the NSP diet (P < .10); 118 and 90
      kJ.kg-.75.d-1, respectively. During the dark phase of the day (from 2000 to 0800)
      activity-related heat production was 8 kJ.kg-.75.d-1 higher for the starch fed
      pigs than for those fed the NSP diet (P > .1) whereas during the light phase,
      this difference was 48 kJ.kg-.75.d-1 (P < .10). Retained energy was similar for
      both treatments. These results show that dietary composition can change physical
      activity of pigs and thereby affect their energy utilization.

PMID- 8880426
TI  - Riboflavin nutrition of sows.
AB  - Two experiments were conducted to evaluate the response of sows to high levels of
      dietary riboflavin. Responses evaluated were erythrocyte glutathione reductase
      activity coefficient (EGRAC, a biochemical indicator of riboflavin status) and
      reproductive performance. In Exp. 1, eight sows were fed diets either slightly
      deficient or superadequate in riboflavin throughout a reproductive cycle,
      beginning in midgestation. The EGRAC values confirmed the slight deficiency (P <
      .01) but did not clearly show a time when the sow is most likely to be deficient
      in riboflavin. In Exp. 2, 118 sows at two farms were fed diets providing 10
      (control, 1.4 times the NRC [1988] requirement estimate), 60, 110, or 160 mg of
      riboflavin/d for 21 d beginning at breeding, and the control level through the
      remainder of the reproductive cycle. The percentage of sows farrowing tended to
      be lower (P < .10) for the control sows than for sows fed the other treatments
      (66.7, 85.7, 93.3, and 86.7% for 10, 60, 110, and 160 mg/d, respectively). This
      response is similar to other results reported previously. No other measure of
      reproductive performance nor EGRAC measured at any of five stages of the
      reproductive cycle, was affected by treatment. These results suggest that massive
      riboflavin supplementation of the sows' diet during early pregnancy may increase
      the percentage of farrowing but does no increase litter size.

PMID- 8880427
TI  - Follicular growth and maturation in hyperprolific and large white sows.
AB  - The mechanisms whereby hyperprolific sows achieve their increased ovulation rate
      (+5 oocytes on average) compared with normal Large White sows were explored in
      this study. The following specific questions were asked. Is increased ovulation
      rate related to 1) increased follicular populations within the ovaries or 2)
      alterations in terminal follicular growth and maturation? The population of
      antral follicles in six sows of each genotype was studied using histological
      techniques on ovaries obtained at the preovulatory stage. No difference between
      the total number of antral follicles, number of healthy or atretic follicles in
      specific size classes, and in size of the preovulatory follicles could be
      detected. The number of granulosa cells contained in preovulatory follicles was
      also similar between genotypes. Terminal follicular growth and maturation were
      studied in 15 sows of each genotype killed at d 1, 3, or 5 (n = 5.d-1.genotype-1)
      after the end of Regumate administration (d 0). Small (< or = 3.5 mm) follicles
      were counted, and follicles > 3.5 mm were dissected, measured, and incubated in
      vitro. Steroid concentrations (estradiol and testosterone) in culture medium were
      then measured. The two genotypes differed in the patterns of growth of their
      ovulatory follicles, because at d 3 all ovulatory follicles were obvious in Large
      White sows. In contrast, between d 3 and 5, seven additional ovulatory follicles
      grew in hyperprolific sows. Differences in follicular maturation between
      genotypes were also detected. Whereas testosterone concentrations in culture
      medium were similar in the two genotypes, estradiol concentrations were markedly
      (P < .01) increased in hyperprolific follicles. This indicates that these
      follicles may have an increased aromatizing ability. How this generates the
      altered pattern of follicular growth and the increased ovulation rate of
      hyperprolific sows remains to be established.

PMID- 8880428
TI  - Effect of energy balance and somatotropin on insulin-like growth factor I in
      serum and on weight and progesterone of corpus luteum in heifers.
AB  - Holstein heifers (approximately 1 yr old) were fed to be in negative energy
      balance (n = 14; NEB) or positive energy balance (n = 15; PEB) during four
      estrous cycles. Each heifer was given PGF2 alpha to control the timing of fourth
      estrus. From 1 d after PGF2 alpha injection until 10 d after estrus, half of the
      heifers were injected daily with 14 mg of somatotropin (bST), and the corpus
      luteum (CL) was collected on d 10. Heifers in NEB had less IGF-I in serum (P <
      .01), smaller CL (P < .01), and less progesterone in CL (P < .01) than heifers in
      PEB. Exogenous bST increased (P < .01) IGF-I in serum, but this increase was
      greater in heifers in PEB than those in NEB (P < .01 for interaction of energy
      balance and bST). Nonetheless, bST did not alter weight or progesterone content
      of the CL in either energy balance group. In addition, serum IGF-I during the
      first 10 d after estrus was not correlated to luteal weight and only weakly
      correlated (r = .3) with luteal progesterone content. We conclude that exogenous
      bST given during luteal development does not alter growth or progesterone content
      of the CL in heifers. Reduced concentration of IGF-I in serum during luteal
      development does not account for suppressed luteal growth and progesterone
      synthesis of heifers in NEB.

PMID- 8880429
TI  - Effect of clenbuterol on growth and body composition during food restriction in
      rats.
AB  - Clenbuterol was administered 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 estimated requirement for
      energy maintenance. Untreated groups at each level of energy intake were also
      included. There was no effect of clenbuterol on food intake in the ad libitum
      group, but the drug produced significant increases in body weight, feed
      efficiency, and carcass weight, dressing and protein content at all three levels
      of energy intake. This effect of clenbuterol was particularly noticeable in the
      restricted animals. Clenbuterol caused changes in body composition (increased
      percentage of water and protein, decreased percentage of fat) in the ad libitum
      rats but had no effect in the restricted groups. The reduction in the growth of
      the viscera caused by energy restriction was not affected by clenbuterol, apart
      from in the 110% restricted group, where the gastrointestinal tract was 26%
      heavier in the clenbuterol-treated rats. The results show that the growth
      anabolic actions of clenbuterol can be sustained and may be even more marked in
      rats fed restrictively than in those given ad libitum access to feed.

PMID- 8880430
TI  - Effects of dietary fat and season on steroid hormonal profiles before parturition
      and on hormonal, cholesterol, triglycerides, follicular patterns, and postpartum
      reproduction in Brahman cows.
AB  - Spring-calving Brahman cows (S) artificially inseminated to Brahman, Angus, or
      Tuli sires and fall-calving Brahman cows (F) naturally bred to Brahman were
      allotted randomly to receive 3.74% (LF; n = 9 S and 6 F), 5.20% (MF; n = 8 S and
      6 F), or 6.55% dietary fat (HF; n = 8 S). Diets were formulated to contain
      differing fatty acid concentrations and to be isocaloric and isonitrogenous. Cows
      were bled and fed twice daily from 2 wk before expected calving date through d 21
      after calving. Ultrasonography was performed on d 14 and 21 after calving. From d
      21 to 90 after calving a sterile bull equipped with a chin-ball marker was placed
      with the cows to aid in estrus detection. In both seasons progesterone decreased
      (P < .01) and estradiol-17 beta increased (P < .01) as parturition approached.
      Cows receiving MF and HF had increased (P < .01) total numbers of follicles
      compared to LF cows, and cows receiving MF had larger (P < .01) follicles. During
      the spring, cows receiving HF and cows bred to Brahman or Tuli sires had longer
      (P < .01) gestation lengths. Progesterone concentrations before calving were
      affected (P < .01) by treatment x sire and estradiol-17 beta by a time x
      treatment interaction (P < .01). Cholesterol after calving was higher (P < .01)
      in HF cows than in LF or MF cows. In the fall, LF cows had heavier (P < .01)
      calves than cows receiving MF. Birth weight was also affected (P < .01) by
      treatment x sex of calf. Progesterone was affected (P < .01) by treatment x sex
      of calf. Estradiol-17 beta was affected (P < .01) by sex of calf and treatment x
      sex of calf. Across seasons, by d 90 after calving, 9 of 15 (60%) LF and 11 of 15
      (73.3%) MF cows showed estrual behavior. Cows in the spring had increased (P <
      .01) numbers and larger follicles compared to the fall. In conclusion, dietary
      fat may influence steroid hormone concentrations before calving, calf birth
      weight and postpartum follicular populations; furthermore, follicular populations
      may also be influenced by season.

PMID- 8880431
TI  - Technical note: porcine non-surgical embryo transfer.
AB  - The cervix is a barrier for transferring porcine embryos non-surgically. A non
      surgical embryo transfer instrument composed of four parts has been developed
      that allows the delivery of embryos into the lumen of one uterine horn. Part 1, a
      modified artificial insemination spirette, is used to produce a cervical lock and
      to assist in manipulating Part 2 through the cervix. Part 2 is made of stainless
      steel tubing with a unique curved tip that can be manipulated through the folds
      of the cervix. Part 3 is a testing bar to ensure that the tip of Part 2 reaches
      the bifurcation of the uterus. Part 4, a disposable tubing complex for embryo
      delivery, is composed of a soft plastic leader tubing, a double opened connector
      for embryo loading and unloading, a semi-hard plastic tubing, and a hard tubing
      with a water-sealable plunger. Embryos (4-cell to blastocyst stages) were
      surgically collected and maintained in vitro up to 5 h before the non-surgical
      embryo transfer. Five of 16 recipients became pregnant (31%) and farrowed an
      average of 6.2 +/- 3.1 pigs per litter. This easily learned non-surgical embryo
      transfer technique will simplify embryo transfer in the swine industry and may
      lead to improvements in swine breeding and scientific research.

PMID- 8880432
TI  - Comparison of Marshall and Surrey ryegrass for continuous and rotational grazing.
AB  - 'Surrey' ryegrass (Lolium multiflorum Lam.) has produced well in clipping yield
      trials across Louisiana, but yield trials do not always predict how well the
      forage supports performance under grazing conditions. This trial compared Surrey
      ryegrass with 'Marshall' ryegrass grazed continuously or rotationally. Two
      pastures of Surrey and two pastures of Marshall that had been subdivided into six
      paddocks each were used in 2 yr. Yearling steers grazed the pastures. In the 1st
      yr, pastures within a cultivar were either continuously or rotationally grazed.
      Thus, animal performance on the rotationally grazed treatments was unreplicated
      and the data were not included in the statistical analysis. In the 2nd yr, each
      pasture contained both continuous and rotational groups of cattle. Cattle gains
      for the two cultivars were not different in either yr 1 (P > .26) or yr 2 (P >
      .17). In yr 2, continuous grazing allowed for greater individual animal gains (P
      = .03) than rotational grazing. However, the lower stocking rate of continuously
      grazed paddocks resulted in a decreased pasture gain (P = .001) of 301 compared
      with 403 kg/ha for the rotationally grazed paddocks. Forage quality was not
      different between Surrey and Marshall ryegrass, but there was a tendency (P =
      .12) for Surrey to have less forage mass during yr 1. Overall, continuously
      grazed paddocks had lower CP and NDF and higher in vitro true digestibility than
      rotationally grazed paddocks. Surrey was equivalent to Marshall ryegrass in
      animal performance and quality, and continuous grazing provided higher individual
      animal performance but lower performance on a gain per hectare basis than
      rotational grazing.

PMID- 8880433
TI  - In vitro inhibition of microbial methane production by 9,10-anthraquinone.
AB  - Monensin, 2,2-dichloroacetamide, and 9,10-anthraquinone were incubated for 24 h
      in ruminal fluid and buffer with 100:0, 50:50, and 10:90 forage-concentrate
      diets. Monensin (.5 ppm of the fluid) increased (P < .05) the molar proportion of
      propionate in the 50 and 100% forage diets but not in the high concentrate diet.
      At the same level of addition, 2,2-dichloroacetamide increased (P < .05) the
      molar proportion of propionate only in the 50:50 forage-concentrate diet.
      Relative to control cultures, monensin and 2,2-dichloroacetamide numerically
      decreased methane production in the 10 and 100% forage diets and decreased (P <
      .05) methane in the 50% forage diet. Hydrogen production was unaffected by
      treatment. Lack of an effect on fermentation end products in the high concentrate
      diet was probably a result of the low dose levels. In general, increasing levels
      of 9,10-anthraquinone (.5, 1.0, and 5.0 ppm) reduced total VFA concentration and
      the molar proportion of acetate, and increased propionate, butyrate and valerate.
      Increasing levels of 9,10-anthraquinone caused linear and quadratic decreases (P
      < .05) in methane production, and increases (P < .05) in hydrogen. There were no
      consistent effects on ammonia concentration in culture fluid from any of the
      compounds. In continuous culture of a 10:90 forage-concentrate diet, addition of
      9,10-anthraquinone (10 ppm of the fluid/12 h) caused changes similar to those
      observed in batch culture with the exception of a decreased (P < .05) molar
      percentage of propionate, which may have been due to the high dose. The data are
      interpreted to indicate that 9,10-anthraquinone has the ability to alter in vitro
      microbial fermentation.

PMID- 8880434
TI  - Rapid communication: cloning and sequencing of a canine beta 2-adrenergic
      receptor cDNA.

PMID- 8880435
TI  - Gas transfer and blood compatibility of fluorinated polyimide membranes.
AB  - Fluorinated polyimide derived from 2,2'-bis(3,4-dicarboxyphenyl)
      hexafluoropropane dianhydride (6FDA) and bis[4-(4-aminophenoxy) phenyl]sulfone
      (APPS) was synthesized to develop a novel membrane oxygenator combining excellent
      gas transfer and blood compatibility. The asymmetric gas exchange membranes of
      6FDA-APPS made by a dry/wet process consisted of an ultrathin and defect-free
      skin layer supported by a porous substructure. O2 transfer through the 6FDA-APPS
      membrane was extremely augmented as compared with that of the presently available
      membrane, poly(dimethylsiloxane), and the previously reported 6FDA-DDS membrane.
      Since CO2 transfer through the 6FDA-APPS membrane increased with a decrease in
      CO2 pressure according to dual-mode transport theory, CO2 from the membrane was
      selectively removed at low CO2 pressure. For the evaluation of in vitro blood
      compatibility, the platelet adhesion and the plasma protein adsorption on the
      surface of the 6FDA-APPS membrane were observed by using scanning electron
      microscopy and the amounts of platelet and plasma protein were determined by an
      amino acid analyzer. The results indicated that the fluorinated polyimide
      membranes showed excellent blood compatibility.

PMID- 8880436
TI  - A new plasma-based method to promote cell adhesion on micrometric tracks on
      polystyrene substrates.
AB  - A new procedure has been developed in order to obtain heterogeneous polymer
      surfaces for the promotion of cell adhesion. For this purpose, a microelectronic
      photosensitive resin was spin coated on polystyrene (PS) substrates. The resin
      was then submitted to UV light irradiation through a mask and partially
      developed. The sample was further submitted to a plasma oxygen discharge prior to
      dissolution of the remaining resin. The characterization by time of flight
      secondary ion mass spectrometry (ToF SIMS), X-ray photoelectron spectroscopy
      (XPS), and dynamic contact angle (DCA) allowed us to conclude that hydrophilic
      paths were created on the more hydrophobic PS substrate together with the
      complete removal of the resin. In order to optimize cell adhesion contrast, the
      modified surfaces were then conditioned with a solution containing both a
      surfactant (pluronic F68) and a protein. Two different proteins were tested
      (collagen I and fibronectin). PC12 cell cultures on those conditioned surfaces
      showed that cell adhesion occurs only on the hydrophilic tracks. ToF SIMS spectra
      and images recorded on those substrates revealed the presence of the proteins
      only in the hydrophilic tracks. In the same time, the surfactant is suspected to
      adsorb mainly on the hydrophobic areas of the samples.

PMID- 8880437
TI  - Mucoadhesive poly(vinyl alcohol) hydrogels produced by freezing/thawing
      processes: applications in the development of wound healing systems.
AB  - Ultrapure poly(vinyl alcohol) (PVA) hydrogels were prepared by exposing an
      aqueous solution of 15 or 20 wt% PVA to repeated cycles of freezing for 6 or 12 h
      at -20 degrees C and thawing for 2 hours at 25 degrees C. The adhesive
      characteristics of the PVA gels in contact with a reconstituted mucus surface
      were quantified using a tensile technique. As the number of freezing/thawing
      cycles increased, the work of fracture (adhesion) decreased due to the increase
      in the PVA degree of crystallinity. Crystallinity was determined using
      differential scanning calorimetry. PVA gels prepared from the 20 wt% solution and
      exposed to two cycles of freezing/thawing exhibited the largest work of adhesion.
      Drug delivery studies were conducted with ketanserin, a wound healing enhancer.
      Release studies were conducted using PVA samples prepared from a 20-wt% solution
      that were exposed to two or three freezing cycles for 12 h followed by thawing
      for 2 h. Results from the release of the drug from the PVA sample exposed to two
      cycles showed that approximately 80% of the ketanserin was released within 4 h.

PMID- 8880438
TI  - The incorporation and release of bovine serum albumin from poly(beta
      hydroxybutyrate-hydroxyvalerate) microspheres.
AB  - Spherical microporous matrix type microspheres composed of 330 kD P(HB-HV) (10.8%
      HV) 20%PCL II containing a range of %BSA loadings have been fabricated using a
      single emulsion technique with solvent evaporation. Microspheres were generated
      in high yield (> 75%) and the percentage incorporation of BSA had no significant
      effect on microsphere size distribution, typically 6-50 microns in diameter with
      a mean of 26.28 +/- 2.34 microns, n = 25, for 20% BSA loaded microspheres. The
      loss of BSA both by partitioning into the aqueous continuous phase and through
      micropores generated during the precipitation of the fabrication polymer
      concomitant with solvent evaporation resulted in a low encapsulation efficiency
      (< 15%). When the total cumulative release of BSA was expressed as a percentage
      of the actual total BSA incorporated, BSA release was only marginally influenced
      by the theoretical percentage loading suggesting that the amount and duration of
      BSA release in vitro was initially influenced as much by micropore number and
      diameter as by the extent of matrix BSA loading and detectable levels of BSA
      release could be monitored for up to 24 days.

PMID- 8880439
TI  - In vitro biodegradation of poly(beta-hydroxybutyrate-hydroxyvalerate)
      microspheres exposed to Hanks' buffer, newborn calf serum, pancreatin and
      synthetic gastric juice.
AB  - Spherical BSA loaded microporous matrix type microspheres composed of P(HB-HV)
      blended with 20% PCL II and fabricated using 0/W emulsification with solvent
      evaporation have been incubated in Hanks' buffer, pH 7.4; newborn calf serum;
      1.5% pancreatin and synthetic gastric juice over 30 days and their percentage
      weight loss (PWL) and changes in ultrastructural morphology monitored by
      gravimetry and SEM respectively. The greatest percentage weight loss was observed
      after incubation in newborn calf serum and decreased in the order newborn calf
      serum > pancreatin > synthetic gastric juice > Hanks' buffer. Only incubation in
      synthetic gastric juice and Hanks' buffer produced a significant increase in PWL
      with increasing theoretical percentage loading. Incubation in Hanks' buffer
      produced limited surface erosion leading to an increase in micropore diameter and
      the coalescence of micropores to from surface pits. With pancreatin, surface
      erosion led to the disappearance of surface micropores and a reduction in
      microsphere diameter. Subsequent fracturing of the microsphere surface
      facilitated the breakup of the matrix. In synthetic gastric juice there was
      little surface erosion and surface flaking and bulk erosion were responsible for
      the breakup of the matrix. In newborn calf serum, spherical shape was maintained
      despite a reduction in microsphere diameter. Bulk erosion in the form of large
      macroporous pits extending deep into the matrix gave the microspheres a hollow
      appearance. The enhanced biodegradation in NCS and significant surface erosion in
      pancreatin was assumed to be due to the effects of exogenous enzyme activity in
      addition to simple ester hydrolysis.

PMID- 8880440
TI  - Synthesis and cytotoxic activity of dextran carrying cis-dichloro(cyclohexane
      trans-l-1,2-diamine)platinum(II) complex.
AB  - cis-Dichloro(cyclohexane-trans-l-1,2-diamine)platinum(II) (Dach-Pt(chlorato)), is
      a platinum complex which is expected to exhibit higher antitumor activity than,
      and show no cross resistance with, cisplatin. However, its strong side-effects
      and low water-solubility have also been cited. We report that polymer/antitumor
      drug conjugates shows reduced side-effects and high antitumor activity. In order
      to provide a macromolecular prodrug of Dach-Pt having reduced side-effects and
      high water-solubility, we synthesized polymer conjugates of Dach-Pt and dextran
      derivatives having carboxylic acid groups, oxidized-dextran (OX-Dex)/Dach-Pt
      conjugate, and carboxymethyl-dextran(CM-Dex)/Dach-Pt conjugate. The cytotoxic
      activities of the conjugates were investigated against p388D1 lymphocytic
      leukemia cells in vitro. The OX-Dex/Dach-Pt conjugate showed almost the same
      level of cytotoxic activity as free Dach-Pt(chlorato). Although the cytotoxic
      activity of free Dach-Pt(chlorato) was decreased by incubation in medium with
      serum, the OX-Dex/Dach-Pt conjugate kept its cytotoxic activity in higher level
      after 24 h incubation in medium with serum. These results suggested that the
      stability of Dach-Pt molecule in the medium was increased and cytotoxic activity
      of Dach-Pt was not decreased by fixing to OX-Dex.

PMID- 8880441
TI  - Effect of ligand orientation on hepatocyte attachment onto the poly(N-p
      vinylbenzyl-o-beta-D-galactopyranosyl-D-gluconamide) as a model ligand of
      asialoglycoprotein.
AB  - The orientation effect of galactose ligand on hepatocyte attachment was
      investigated. Poly(N-p-vinylbenzyl-o-beta-D-galactopyranosyl-D-gluconamide
      )(PVLA), a beta-galactose-carrying styrene homopolymer, was used as a model
      ligand for the asialoglycoprotein receptors on hepatocytes. PVLA was transferred
      onto the poly(gamma-benzyl L-glutamate) (PBLG) or PBLG/poly(ethylene glycol)
      (PEG)PBLG Langmuir-Blodgett (LB) films as the monolayer level. The dichroic
      fluorescence values of the confocal microscope indicated that the PVLA
      transferred onto the LB films was located with a preferential orientation of its
      molecular axes with regard to the direction of the alpha-helix of polypeptide.
      Hepatocyte recognized well-oriented galactose moieties of the surface of PVLA
      through asialoglycoprotein receptors.

PMID- 8880442
TI  - Modification of poly(ether urethane)elastomers by incorporation of
      poly(isobutylene)glycol. Relation between polymer properties and thrombogenicity.
AB  - Non-polar hydrophobic poly(isobutylene)glycol (PIBG) was substituted for
      poly(tetramethylene ether)glycol (PTMEG) in poly(ether urethanes) based on 4,4'
      methylenebis-(phenylisocyanate) (MDI) and 1,4-butanediol (BD) as chain extender.
      Two series of polyurethanes differing in their soft segment length, polymer
      composition, and hard segment content were studied by dynamic mechanical analysis
      (DMA) and static, as well as dynamic, contact angle measurements. The
      thrombogenicity of these polymers was characterized by studying the adhesion and
      activation of platelets using ELISA for GMP 140 and fluorescence microscopy. It
      was found by DMA that in PIBG-containing polyurethanes (PUE) exist soft domains
      containing hard segments, strictly separated hard segment domains, and hard
      segments partially mixed with soft segments. Contact angle measurements revealed
      that 25% PIBG or even less, are sufficient for a remarkable enrichment of these
      non-polar soft segments on the polymer surface. The platelet adhesion/activation
      on these materials was demonstrated to increase with the rise in hard segment
      content, as well as with an enhancement of the PIBG content. However, comparison
      of PIBG-containing PUE with medical applied polypropylene and pellethane
      expressed that PUE with PIBG content equal or less 25% have excellent
      haemocompatibility.

PMID- 8880443
TI  - Kinetic analysis of ethanol production from glucose fermentation by yeast cells
      immobilized onto ceramic supports.
AB  - Porous ceramic supports have been developed and utilized for the immobilization
      of yeast cells to produce ethanol by the fermentation of glucose. The
      relationship between the porous structure of the ceramic support and the quantity
      of yeast cells immobilized and the production of ethanol by the fermentation have
      been investigated. A comparison of the properties of the ceramic supports with
      those of a calcium alginate gel indicated that the ceramics are the better of the
      two types of material and have potential for industrial application.

PMID- 8880444
TI  - The development of the specialty of oral and maxillofacial surgery in the
      European Union.

PMID- 8880445
TI  - Historical development of orthognathic surgery.

PMID- 8880446
TI  - Involvement of the temporomandibular joints in ankylosing spondylitis
      (Bechterew's disease).

PMID- 8880447
TI  - Prefabrication of combined scapula flaps for microsurgical reconstruction in oro
      maxillofacial defects: a new method.
AB  - Nowadays, in congenital or acquired large oro-maxillofacial defects,
      microsurgical reconstruction is mainly performed by revascularized osseous,
      osteocutaneous, or osteomyocutaneous distant flaps. The aims of reconstruction
      include not only restoration of stability and aesthetic contour, but also the
      restoration of a functioning 'chewing organ'. In addition to bulkiness of the
      flaps, the stepwise surgical procedure (microvascular reconstruction,
      osseointegration of implants, secondary correction of flaps including
      preprosthetic surgery, etc.) prevents physiological oral function for a long
      time, and has some implications for creating an alternative method of
      microsurgical reconstruction with newly designed flaps. For reconstruction in
      maxillary and midface defects we prefer the use of the scapula flap. Since modern
      diagnostic methods allow comprehensive planning and defining of all relevant
      anatomical and functional factors in advance, the 'simultaneous' microvascular
      reconstruction by prefabricated scapula flaps has become possible and offers some
      advantages. The tissue prefabrication results in osseointegrated implants and
      thin mucosal linings with stable peri-implant soft tissue conditions at the time
      of microsurgical reconstruction. Postoperatively, after immediate dental
      restoration full oral function is attained. The 'simultaneous' reconstruction
      improves the psychosocial situation of the patient considerably.

PMID- 8880448
TI  - Craniofacial osteotomies to facilitate resection of large tumours of the anterior
      skull base.
AB  - Large tumours of the anterior cranial fossa can be a major challenge to the
      neurosurgeon or the maxillofacial surgeon. However, skull base approaches
      facilitate their resection. We describe our experience with the extended
      subfrontal approach in treating tumours of the anterior cranial base. This
      approach was performed on 29 patients with large tumours of the anterior skull
      base. The final outcome in all 29 patients was favourable in terms of total
      resection of the tumour with minimal subsequent neurological deficit. Two
      patients developed transient oedema of the frontal lobes without persistent
      neurological sequelae. Another patient developed a postoperative cerebrospinal
      fluid fistula that was successfully repaired. The patients were followed for a
      period ranging from 6 to 28 months. There was no recurrence. The operative
      technique is described. En bloc removal of the roofs of the orbits and part of
      the anterior cranial fossa permits wide exposure of the lesion with minimal brain
      retraction. Reconstruction of the anterior cranial base should be meticulous to
      avoid cerebrospinal fluid leaks and subsequent meningitis. Loss of smell is a
      sequel to this approach. The possible risks and some important technical details
      are highlighted.

PMID- 8880449
TI  - An anatomical classification of maxillary ameloblastoma as an aid to surgical
      treatment.
AB  - Maxillary ameloblastoma is a different entity from its mandibular counterpart. It
      is reported to behave more aggressively and have a poorer prognosis. Eleven
      maxillary ameloblastomas (three recurrent) are reported with a follow-up ranging
      from 1 month to 12 years with no recurrences. It is proposed that radical
      treatment of these tumours, with good reconstruction, can give satisfactory
      function and survival. To that end, the tumours have been classified as to their
      position in the maxilla and surgical resection related to this.

PMID- 8880450
TI  - Endosteal implants in the irradiated lower jaw.
AB  - Since 1990 Endosteal implants have been inserted in the irradiated lower jaw at
      our clinic. IMZ implants have been used for dental rehabilitation in 26 patients
      (21 male, 5 female) suffering from squamous cell carcinomas stage T2-T4 136. The
      implants were either placed in local bone and soft tissue (group 1, n = 60
      implants), or in local bone after marginal mandibulectomy and transplanted soft
      tissue (group 2, n = 26 implants), or in transplanted bone and soft tissue (group
      3, n = 52 implants). Life-table analysis according to Kaplan-Meier demonstrated a
      3-year implant survival rate of 87.8% in Group 1, 69.1% in Group 2 and 58.3% in
      Group 3. There was no statistical significant difference in the amount of
      marginal bone loss and the degree of marginal infection between the three groups
      (P > 0.29). Major complications: A mandibular fracture passing through an empty
      implant socket 8 months after implant loss (Group 2) was caused by postradiation
      osteonecrosis; implant removal and bone resection was mandatory. The poor results
      of the bone graft group may be explained by two patients, in whom simultaneous
      placement of implants in nonvascularized bone grafts was carried out, intraoral
      tissue breakdown led to graft failure and loss of the implants (n = 10).

PMID- 8880451
TI  - Orbital emphysema and the medial orbital wall: a review of the literature with
      particular reference to that associated with indirect trauma and possible
      blindness.
AB  - Orbital emphysema is not an uncommon finding following fractures of the facial
      skeleton. Both its significance as a threat to sight and its diagnostic value may
      well be underestimated. Fractures of the paranasal sinuses may occur as a result
      of indirect trauma. This article reviews the literature on the subject with
      particular reference to blindness as a possible sequel. Two cases of orbital wall
      fracture that occurred as a result of indirect trauma and which produced orbital
      emphysema are discussed.

PMID- 8880452
TI  - Failure of onlay bone grafts to integrate over the calvarial suture: observations
      in adult isogeneic rats.
AB  - Bone grafting constitutes an important tool in cranio-maxillofacial skeletal
      reconstruction and augmentation. Much effort has been directed to improve graft
      survival and volumetric maintenance. The effects of the sutural tissue proper on
      graft incorporation has not yet been explored. The purpose of this report was to
      analyze the effects of positioning an onlay graft over a non-growing sutural
      region. Twelve adult rats received femoral or tibial uni- or bicortical grafts
      placed over the temporal suture. The findings were assessed by routine microscopy
      and immunohistochemistry after 4, 12, and 20 weeks. The sutural tissue expanded
      between the graft and the host bed in an umbrella-like pattern, which locally
      inhibited graft incorporation. Of the tested cartilage and bone proteins and
      proteoglycans, labelling was distinct only for osteopontin and fibromodulin,
      indicating a moderate remodelling activity in the area. The importance and
      consequences of the findings are discussed.

PMID- 8880453
TI  - Nucleotide sequence of the bovine vitamin D3 receptor.

PMID- 8880454
TI  - Identification of an antihypertensive peptide from casein hydrolysate produced by
      a proteinase from Lactobacillus helveticus CP790.
AB  - Casein hydrolysate, produced by an extracellular proteinase from Lactobacillus
      helveticus CP790, was fractionated by two-step reverse-phase HPLC. Only one
      fraction showed antihypertensive activity as measured by systolic blood pressure
      in spontaneously hypertensive rats after oral administration. Ten peptides in the
      fraction were further purified and identified by analysis of amino acid
      sequences. Each identified peptide was chemically synthesized, and the
      antihypertensive activity of each peptide was evaluated in spontaneously
      hypertensive rats. The synthetic peptide with a sequence of Lys-Val-Leu-Pro-Val
      Pro-Gln, found in beta-casein, indicated strong antihypertensive activity from 2
      to 10 h after oral administration of 2 mg of peptide/kg of BW, and the effect was
      maximal at 6 h after oral administration (-31.5 +/- 5.6 mm Hg). Moreover, the
      antihypertensive effect of the peptide was dependent on the dosage of peptide
      from 0.5 to 2 mg of peptide/kg of BW. Interestingly, the antihypertensive peptide
      showed lower inhibitory activity of angiotensin I-converting enzyme, but the
      activity was increased after pancreatin digestion.

PMID- 8880455
TI  - Odorous constituents of ovine milk in relationship to diet.
AB  - The neutral volatile compounds of ovine milk from ewes fed on natural pasture,
      grass meadow, and on mixed grain rations were isolated by distillation under
      vacuum and then collected in traps that were cooled with liquid nitrogen. The
      distillate was extracted with dichloromethane, and the extract obtained was
      analyzed using high resolution gas chromatography and high resolution gas
      chromatography coupled to mass spectrometry. Seventy compounds were identified
      and quantitatively determined. The volatile compounds obtained were mainly
      esters, aldehydes, alcohols, ketones, nitrogen compounds, sulfur compounds,
      aromatic hydrocarbons, and lactones. The olfactometric indices and olfactory
      properties of 16 compounds were determined by gas chromatography and
      olfactometry. All of the substances were present in all three milk types with the
      exception of two sesquiterpenes, which were not detected in the milk from ewes
      fed the mixed grain ration. The two sesquiterpenes were absent also in ovine
      cheese obtained from milk from ewes fed the mixed grain ration, but the two
      sesquiterpenes were identified in cheese produced from milk of sheep fed on
      natural pasture. The presence of these constituents in the milk can be
      significant because of their potential role in determining milk and cheese
      flavor. Accordingly, cheese obtained during summer may be identified using
      sesquiterpenes as chemical markers of the milk used to make cheese.

PMID- 8880456
TI  - A method for isolating beta-casein.
AB  - A new method was developed for obtaining pure beta-CN. Calcium caseinate (3%) was
      reconstituted, renneted to form a gel, cooled (4 degrees C) to allow beta-CN
      dissociation from the caseinate gel, and centrifuged. The supernatant was warmed
      to 30 degrees C, precipitating pure beta-CN from solution. Large quantities of
      beta-CN were recovered by scaling-up this procedure, but these beta-CN
      preparations were less pure than the beta-CN that was prepared on a smaller
      scale. Chromatography (FPLC) and urea-PAGE showed beta-CN to be the main
      component in the precipitate. Chymosin, used to form the caseinate gel, did not
      extensively hydrolyze beta-CN under the conditions of these experiments. Calcium
      concentration, cooling time, and caseinate concentration influenced the recovery
      of beta-CN. Maximum recovery of beta-CN, under the experimental conditions used,
      occurred at 10 mM calcium, 48 h of cooling, and 3% caseinate concentration.

PMID- 8880457
TI  - Enhancing bactericidal activity of bovine lymphoid cells during the
      periparturient period.
AB  - The antibacterial activity of bovine lymphocytes was evaluated following in vitro
      stimulation with interleukin-2. Mononuclear cells were isolated from the blood,
      lymph node, and mammary parenchymal tissue of four lactating and four
      periparturient dairy cows. These cells were evaluated for antibacterial activity
      against Staphylococcus aureus following incubation for 48 h with or without
      interleukin-2. Cultures stimulated with interleukin-2 had higher bactericidal
      activity of all three isolated cell populations than did unstimulated cultures,
      regardless of lactational stage. This observation suggests that this effector
      function may possibly be activated in vivo and may potentially increase mammary
      gland resistance to bacterial infections during periods of increased
      susceptibility. Flow cytometric analysis of the cultured cells revealed that
      antibacterial effector cells were mainly CD2+ and were depleted of macrophages.
      Despite shifts in CD4+, CD8+, and gamma delta T lymphocytes during the
      periparturient period, bactericidal activity was similar among the three cell
      sources. This similarity suggests that these lymphocyte phenotypes might not be
      directly responsible for this effector function. Identification of the
      antibacterial effector phenotype and its mechanism of action may lead to
      immunoregulatory strategies aimed at enhancing this novel bactericidal function.

PMID- 8880458
TI  - Cell culture system for studying bovine neutrophil diapedesis.
AB  - Neutrophils are the major defense against bacterial infection in the bovine
      mammary gland. Neutrophils migrate from blood into the lumen of the gland in
      response to inflammatory stimuli. This study describes the development of a
      system of cell culture that can be used to study neutrophil diapedesis through
      secretory and ductal mammary epithelial barriers. The culture system consists of
      successive layers of collagen, fibroblasts, collagen, and a confluent monolayer
      of secretory or ductal epithelial cells layered on a porous membrane. Confluence
      was determined by electrical resistance and trypan blue diffusion. Neutrophil
      diapedesis occurred from the basal to the apical surface of the monolayers.
      Purified complement C5a, fetal bovine serum that had been activated by zymosan,
      and fetal bovine serum that had been activated by Escherichia coli induced
      neutrophil diapedesis. Neutrophil diapedesis was greater across ductal cell
      monolayers. Blood neutrophils from five cows differed in their ability to migrate
      through the multilayered culture system in response to C5a. Monoclonal antibodies
      to C5a blocked diapedesis induced by purified C5a but had no effect on diapedesis
      induced by fetal bovine serum that had been activated by zymosan or by fetal
      bovine serum that had been activated by E. coli endotoxin, indicating that
      factors other than C5a were chemotactic for neutrophils. Monomeric IgG2, immune
      complexes, and E. coli endotoxin did not induce neutrophil diapedesis.

PMID- 8880459
TI  - Pyrroline-5-carboxylate reductase in lactating bovine mammary glands.
AB  - The occurrence and subcellular distribution of pyrroline-5-carboxylate reductase
      have been studied in lactating bovine mammary glands. The enzyme appears to have
      only a cursory association with the mitochondrial fraction, because significant
      amounts of the enzyme are found in other membrane-containing fractions and in the
      cytosol. Polyamines stimulate the enzyme in vitro, supporting the mediation of
      cursory attachment to membrane fractions by these compounds. The enzyme is
      selective for NADPH but can utilize NADH as well. Long-chain coenzyme A
      derivatives, which are generated during lipid metabolism, almost completely
      inhibit this enzyme, which is responsible for the synthesis of a portion of the
      proline needed for casein production. Overall, the enzyme concentration in the
      gland correlates well with a role in the conversion of an intermediate, L-delta 1
      pyrroline-5-carboxylate, into proline, an important amino acid for the mammary
      secretory process, especially casein synthesis.

PMID- 8880460
TI  - Local secretion of nitric oxide and the control of mammary blood flow.
AB  - Our objective was to test the hypothesis that local production of the
      vasorelaxant nitric oxide could regulate mammary blood flow. In four lactating
      Saanen goats, the response of mammary blood flow to intraarterial infusion of the
      nitric oxide donor diethylamine NONOate and the inhibitor of nitric oxide
      synthesis N omega-nitro-arginine was measured. Diethylamine NONOate induced a
      rapid and sustained increase of mammary blood flow in the infused gland only,
      suggesting a direct effect on vasculature of the mammary gland. In contrast,
      infusion of N omega-nitro-arginine decreased mammary blood flow by up to 35%, and
      the coinfusion of arginine, the nitric oxide precursor, with N omega-nitro
      arginine markedly reduced its ability to decrease mammary blood flow. The
      distribution of nitric oxide synthase was investigated in cryosections of caprine
      and bovine mammary tissue by histochemical staining for NADPH-diaphorase activity
      and by immunocytochemistry using specific antibodies against two nitric oxide
      synthase isoforms. Both techniques revealed nitric oxide synthase in the vascular
      endothelium and secretory epithelium of the two species. Only antibodies against
      nitric oxide synthase-III showed specific staining. These results suggest that
      the mammary gland produces and responds to nitric oxide and, further, raise the
      possibility that the epithelium may control its own blood supply by secreting
      nitric oxide.

PMID- 8880461
TI  - Treatment with recombinant bovine interferon-tau in utero attenuates secretion of
      prostaglandin F from cultured endometrial epithelial cells.
AB  - Endometrial oxytocin receptors and total production of PGF by endometrial
      epithelial cells were measured in 10 cyclic cows after intrauterine injections of
      recombinant bovine interferon-tau plus BSA or BSA alone. Cows received twice
      daily injections (via intrauterine catheters) of 200 micrograms of recombinant
      bovine interferon-tau plus 1.3 mg of BSA (n = 5) or 1.5 mg of BSA (n = 5) from d
      14 to 17 after estrus. On d 17, the reproductive tracts of each cow was removed
      at slaughter, and endometrial epithelial cells were cultured with 0, 2, or 50
      ng/ml of recombinant bovine interferon-tau. After 24 h, oxytocin (2 x 10(-7) M)
      was added to one-half of the culture wells, and the medium was sampled at 0, 30,
      and 90 min for analysis of total PGF (PGF plus 13, 14-dihydro-15-keto-PGF2
      alpha). In vivo treatment with recombinant bovine interferon-tau + BSA reduced
      total secretion of PGF in culture (1.49 +/- 0.06 vs. 2.80 +/- 0.07 ng/micrograms
      of DNA), but did not block the oxytocin-induced stimulation in total secretion of
      PGF. In vitro treatment of cells with recombinant-bovine interferon-tau did not
      decrease basal secretion of total PGF. Oxytocin receptor binding at d 17 was low
      in both treatments but slightly attenuated in the group treated with recombinant
      bovine interferon-tau.

PMID- 8880462
TI  - Evaluation of timed insemination using a gonadotropin-releasing hormone agonist
      in lactating dairy cows.
AB  - An experiment compared the effectiveness of a timed AI and an AI at observed
      estrus. Lactating dairy cows were injected with PGF2 alpha at 30 +/- a range of 3
      d postpartum, with a GnRH agonist at 65 +/- a range of 3 d, and with PGF2 alpha 7
      d later; control cows (n = 128) were inseminated at detected estrus, but cows in
      the timed AI group (n = 171) received a second injection of GnRH agonist 48 h
      after the injection of PGF2 alpha and were inseminated 16 h later. Control cows
      that were not inseminated within 7 d were resynchronized with GnRH agonist,
      followed 7 d later with an injection of PGF2 alpha. Pregnancy rate was 30.5% for
      control cows and 29.0% for cows in the timed AI group, and conception rate was
      41.5% for control cows and 26.5% for cows in the timed AI group. Days open for
      cows that conceived by 120 d postpartum was 83.6 d for control cows and 79.2 d
      for cows in the timed AI group. Treatment by month interactions indicated that
      pregnancy and conception rates and days open for cows that conceived were more
      consistent across months for cows in the timed AI group. Differences (control vs.
      timed AI) were not detected for overall pregnancy rate by 120 d postpartum (58.8
      +/- 4.7% vs. 56.2 +/- 4.4%). Conception and pregnancy rates at first
      synchronization were influenced positively by body condition and plasma
      concentrations of progesterone at 65 d postpartum. Timed AI was an effective
      alternative for reproductive management.

PMID- 8880463
TI  - Effects of tempered barley on milk yield, intake, and digestion kinetics of
      lactating Holstein cows.
AB  - The effects on milk yield and digestion kinetics were compared when tempered (10%
      water added 24 h prior to processing and feeding), rolled barley and dry, rolled
      barley were fed in trial 1, or tempered, whole barley, and dry, rolled barley
      were fed in trial 2. In trial 1, the diet based on tempered, rolled barley
      resulted in increased milk yield (5%), efficiency (10%), and apparent
      digestibility of dietary DM (6%), NDF (15%), ADF (12%), CP (10%), and starch
      (4%). Mean fractional rate of passage was slower for tempered (7.8%/h) than for
      dry (8.6%/h) barley particles. Mean fractional rate of passage of forage
      particles and rates of digestion of forage and concentrate did not differ. The
      percentage of particle washout from an in situ bag (pore size, 53 mu) was 21% for
      dry barley and 6% for tempered barley, indicating that tempering reduced the pool
      size of small particles in rolled barley. In trial 2, the diet based on tempered,
      whole barley resulted in decreased daily milk yield (5%), efficiency (11%), and
      apparent digestibility of dietary DM (16%), CP (10%), and starch (8%). The
      results indicated that tempered, rolled barley can be effectively used in diets
      for high yielding dairy cows to increase yield and efficiency; however, tempered
      barley must be rolled to achieve these effects.

PMID- 8880464
TI  - Effect of concentrate source and amount in diets on plasma hormone concentrations
      of prepubertal heifers.
AB  - Effects of concentrate source (corn or soybean hulls) and amount (40 or 80% of
      DMI) on plasma hormone concentrations were evaluated for 32 prepubertal Holstein
      heifers in a 2 x 2 factorial design. Blood samples were collected every other day
      from d -4 through d 28 of the experiment and were analyzed for growth hormone,
      prolactin, IGF-1, and glucose. Ruminal samples were collected by esophageal tube
      on d 0, 7, 14, 21, and 28 and were analyzed for VFA content. Serial blood samples
      were collected on either d 25 or 26 at 20-min intervals for 8 h and were used for
      profile analysis of growth hormone and prolactin. Heifers fed 80% concentrate had
      higher IGF-1 concentrations in serum (158.1 vs. 131.9 ng/ml) than did heifers fed
      40% concentrate, and heifers fed corn tended to have higher IGF-1 concentrations
      than heifers fed soybean hulls. Prolactin concentrations in samples that were
      collected every other day were higher for heifers fed the 80% soybean hull diet
      than for those fed 40% concentrate diets or the 80% corn diet. Effects of source
      and amount of concentrate on plasma prolactin concentrations were not evident in
      serial samples. Concentrate source or amount had no effect on plasma growth
      hormone or glucose. At high concentrate intakes, the source (soybean hulls vs.
      corn) affected intake parameters, ruminal VFA content, and prolactin
      concentrations.

PMID- 8880465
TI  - Effects of dietary fat with or without nicotinic acid on nutrient flow to the
      duodenum of dairy cows.
AB  - Four Holstein cows, fitted with ruminal and duodenal cannulas, were utilized in a
      4 x 4 Latin square design to investigate the effects of supplementing nicotinic
      acid to diets that contained 35% alfalfa haylage, 15% corn silage, and either 50%
      of a low fat concentrate or 10% whole raw soybeans and 40% of a high fat
      concentrate containing tallow. Treatments in a 2 x 2 arrangement were 1) low fat,
      no supplemental nicotinic acid; 2) low fat, 12 g/d of nicotinic acid; 3) high
      fat, no supplemental nicotinic acid; and 4) high fat, 12 g/d of nicotinic acid.
      The DMI and OM apparently and truly digested in the rumen and apparently digested
      postruminally were not different among treatments. Addition of fat to the diet
      decreased the concentration of total VFA in ruminal fluid but did not alter the
      molar proportions of any of the VFA; supplementation of nicotinic acid tended to
      decrease the molar proportion of acetate. Amounts of NAN, microbial N, nonammonia
      nonmicrobial N, and AA that flowed to the duodenum were similar among diets. The
      concentration of urea N in plasma decreased, and concentrations of cholesterol
      and triglycerides increased, when cows were fed supplemental fat. Milk
      composition and production of milk, 4% FCM, and milk components were not altered
      by addition of fat or nicotinic acid to the diet. Supplementation of fat or
      nicotinic acid to diets of dairy cows was not beneficial in this experiment.

PMID- 8880466
TI  - Responses in milk constituents to intravascular administration of two mixtures of
      amino acids to dairy cows.
AB  - Four Holstein-Friesian cows were used to investigate the effects of intravascular
      infusions of AA mixtures on milk constituents. Cows were in wk 11 to 28 of
      lactation and were fed a basal concentrate (142 g of CP/kg of DM) and grass
      silage (149 g of CP/kg of DM) in a 60:40 ratio (percentage of DM). Cows were fed
      hourly, and feed intake was fixed at 95% of ad libitum intake for each
      experimental period. Each cow received a 4-d jugular saline infusion, followed by
      a 5-d jugular infusion of a mixture of AA. Two mixtures of AA were used in a
      crossover design. The first mixture contained both the essential AA and non
      essential AA found in milk protein (total AA); this mixture was infused at 400 g
      of AA/d. The other mixture represented the essential AA fraction only and was
      infused at 208 g/d. Infusion of total AA increased milk protein concentration
      from 32.4 to 35.0 g/kg, and essential AA increased milk protein concentration
      from 32.5 to 36.9 g/kg; milk protein yield increased by 87 g/d (total AA) and 143
      g/d (essential AA). Intravascular administration of AA specifically stimulated
      milk protein concentration, and the efficiency with which the AA were used was
      higher than had been previously reported when AA supply was increased either by
      dietary supplementation or by abomasal infusion.

PMID- 8880467
TI  - In situ disappearance of individual proteins and nitrogen from legume forages
      containing varying amounts of tannins.
AB  - In situ degradability of N and proteins were studied in one cultivar of alfalfa
      and red clover and two cultivars each of birdsfoot trefoil and sericea lespedeza.
      Concentrations of tannic acid equivalents (percentage of DM) were 0.68 in one
      cultivar of birds-foot trefoil and 1.77 and 2.78 in the two cultivars of
      lespedeza. The other forages contained essentially no tannins. Forage samples
      were digested in situ for 0, 2, 4, 6, and 12 h. The amount of N remaining at 12 h
      was positively correlated with concentrations of tannin. About 38% of the N
      remained after 12 h in forages with no or low concentrations of tannins, and 86%
      remained in the two cultivars of lespedeza. Total electrophoretically identified
      proteins followed similar trends, but the percentage remaining was less than that
      for N. For all forages, bands were found at molecular masses of 15, 30, 45, 47,
      and 54 kDa. The percentage of 54-kDa protein that remained after 12 h was less
      than that for the other four proteins (23% vs. 37%). No interaction was found
      between forage cultivar and protein species. These results showed that tannins
      reduced ruminal degradation of proteins and that specific forage proteins
      degraded at different rates that were independent of tannin concentration.

PMID- 8880469
TI  - Relationships of polymorphisms for growth hormone and growth hormone receptor
      genes with milk production traits for Italian Holstein-Friesian bulls.
AB  - Allelic variation in the structural or regulatory sequences of growth hormone and
      its receptor genes might directly or indirectly affect milk traits. This
      possibility prompted us to investigate the eventual relationships of restriction
      fragment length polymorphisms at the locus of bovine growth hormone (using TagI
      and MspI restriction enzymes) and its receptor (using TaqI restriction enzyme) to
      PTA of milk production traits of bulls. Ninety-one Italian Holstein-Friesian
      bulls were used in this experiment, and data were analyzed with a fixed linear
      model. The restriction fragment length polymorphisms at the growth hormone locus
      did not affect the milk traits studied. Six restriction enzyme TaqI bands of 7.1,
      6.2, 5.7, 5.4, 4.2, and 3.3 kb with nine patterns were observed after
      hybridization by a cDNA probe containing the coding sequences for the
      intracellular C-terminal part of the receptor. The effect of this polymorphism on
      PTA for milk protein percentage was highly significant and was favorable for the
      rare (6.6%) 5.7- and 5.4-kb pattern. Our results indicate that further study is
      needed to explain the DNA polymorphism and to obtain more definite conclusions
      about effects on milk traits.

PMID- 8880468
TI  - Metabolite and hormonal responses to glucose or propionate infusions in
      periparturient dairy cows supplemented with chromium.
AB  - Two studies were conducted to evaluate the effects of Cr supplementation on blood
      metabolite and hormonal responses of Holstein cows to glucose challenges during
      late pregnancy and early lactation and to propionate challenges during early
      lactation. Eight multiparous and 4 primiparous cows (Experiment 1) and 12
      primiparous cows (Experiment 2) were assigned to one of two treatments: control
      and 0.5 ppm of supplemental Cr. The glucose challenges were performed at 2 wk
      prepartum and at 2 wk postpartum, and the propionate challenges were conducted at
      wk 2 and 6 postpartum. During glucose tolerance tests, Cr supplementation reduced
      the ratio of insulin to glucose and reduced plasma concentrations of insulin and
      triglycerides of primiparous cows during the prepartum period. Chromium
      supplementation decreased plasma Cr of primiparous cows following glucose
      challenge. With supplemental Cr, insulin sensitivity was reduced postpartum,
      particularly for primiparous cows, but insulin sensitivity was increased
      prepartum. Results of this study suggested that primiparous cows experienced Cr
      deficiency during late pregnancy and possibly during early lactation. Following
      propionate infusion, Cr supplementation increased the serum glucose peak,
      increased the area under the response curve for serum glucose, and tended to
      increase IGF-I concentrations. Chromium supplementation tended to reduce the
      ratio of insulin to glucagon. Supplementation might have enhanced gluconeogenesis
      or glycogenolysis. Supplemental Cr also resulted in reduced variability of most
      parameters during both experiments.

PMID- 8880471
TI  - Physical treatments affecting the solid fat content of butter fat: thermal
      treatment of cream and membrane partition of butter oil.
AB  - Seasonal variations of milk fat composition, affecting the solid fat content of
      butter, are used as a model to monitor the texture of the final product. Two
      methods have been investigated: 1) thermal treatment of cream, which is uncertain
      and restricted, and 2) a new membrane separation procedure applied to butter oil
      in a fully hydrophobic medium. Under specific hydrodynamic conditions, a slight
      variation of the composition leads to a magnification of the variation obtained
      on the solid fat. This effect is similar to the seasonal effect, allowing control
      of the final texture of the butter.

PMID- 8880470
TI  - New opportunities from the isolation and utilization of whey proteins.
AB  - Management of dairy whey has often involved implementation of the most economical
      disposal methods, including discharge into waterways and onto fields or simple
      processing into low value commodity powders. These methods have been, and
      continue to be, restricted by environmental regulations and the cyclical
      variations in price associated with commodity products. In any modern regimen for
      whey management, the focus must therefore be on maximizing the value of available
      whey solids through greater and more varied utilization of the whey components.
      The whey protein constituents offer tremendous opportunities. Although whey
      represents a rich source of proteins with diverse food properties for
      nutritional, biological, and functional applications, commercial exploitation of
      these proteins has not been widespread because of a restricted applications base,
      a lack of viable industrial technologies for protein fractionation, and
      inconsistency in product quality. These shortcomings are being addressed through
      the development of novel and commercially relevant whey processing technologies,
      the preparation of new whey protein fractions, and the exploitation of the
      properties of these fractions in food and in nontraditional applications.
      Examples include the following developments: 1) whey proteins as physiologically
      functional food ingredients, 2) alpha-lactalbumin and beta-lactoglobulin as
      nutritional and specialized physically functional food ingredients, and 3) minor
      protein components as specialized food ingredients and an important
      biotechnological reagents. Specific examples include the isolation and
      utilization of lactoferrin and the replacement of fetal bovine serum in tissue
      cell culture applications with a growth factor extract isolated from whey.

PMID- 8880472
TI  - How many ruminal bacteria are there?
AB  - With the development of strictly anaerobic techniques and habitat-simulating
      media, a variety of bacteria were isolated from the rumen in the 1940s and 1950s.
      Based on standard morphological and physiological characteristics, the microbial
      ecosystem of the rumen contains a very complex population of bacteria. In recent
      years, ruminal bacteria have been re-evaluated with newer, more objective, and
      genetically valid methods of classification. Ribosomes are complicated
      structures, and their DNA-encoding sequences are relatively free from selective
      pressure. Because ribosomes have evolved slowly, they provide a long-term natural
      history of evolution. The invariable and hypervariable regions of rRNA genes can
      be used to group bacteria into kingdoms, genera, and species. The 16S rRNA
      sequences have provided a basis for renaming some ruminal species (Bacteroides
      amylophilus is now Ruminobacter amylophilus and Bacteroides succinogenes is now
      Fibrobacter succinogenes) and for classifying at least one recently isolated
      ruminal bacterium (e.g., Clostridium aminophilum). The DNA:DNA hybridization is a
      more sensitive method of assessing bacterial relatedness than is 16S rRNA.
      Bacterial strains within a species should have a high degree of DNA:DNA homology,
      but some species of ruminal bacteria (e.g., Prevotella ruminicola and
      Butyrivibrio fibrisolvens) had highly unrelated strains. Studies of 16S rRNA and
      DNA:DNA hybridization indicate that the diversity of ruminal bacteria has been
      greatly underestimated. Traditional studies of phylogeny of ruminal bacteria were
      stymied by the fastidious growth requirements of many ruminal bacteria, and
      enumeration was tedious and inaccurate. Modern methods of bacterial
      classification do not require in vitro culture and have the potential of
      detecting even a single cell.

PMID- 8880473
TI  - Do ruminal bacteria exchange genetic material?
AB  - This paper discusses the reasons and current evidence for gene transfer between
      ruminal bacteria and other bacteria in the environment, possible routes for
      genetic exchange, and candidate genes. Gene transfer between ruminal bacteria has
      been demonstrated in vitro; however, success has been only minimal in obtaining
      plasmids and other self-transmissible genetic material from ruminal bacteria. The
      application of molecular biology techniques with ruminal microorganisms should
      permit the opportunity for an in vivo assessment of gene transfer. Studies that
      could provide pertinent information for ruminal microbiologists and dairy
      nutritionists are outlined.

PMID- 8880474
TI  - Why do many ruminal bacteria die and lyse so quickly?
AB  - Studies using 15N have indicated that as much as 50% of the microbial mass turns
      over before N passes to the lower gut, and this N recycling significantly
      decreases the availability of microbial protein. Protozoa digest bacteria and
      smaller protozoa, but bacterial protein can turn over even if protozoa are not
      present. Fibrobacter succinogenes cultures lyse even when they are growing, and
      the lysis rate is independent of growth rate. When extracellular sugar is
      depleted, F. succinogenes secretes an extracellular proteinase that inactivates
      the autolysins. This method of autolytic regulation decreases the turnover of
      stationary cells. Bacteriophage and anaeroplasma can cause lysogeny, but, as yet,
      there is little proof that these processes are important determinants of
      bacterial turnover in vivo. Dietary manipulations (e.g., salt feeding and
      particle size reduction) that increase liquid and solid dilution rates can
      increase bacterial flow by decreasing bacterial residence time and turnover. Some
      dead ruminal bacteria are able to maintain their cellular integrity, and the
      ratio of dead to live cells in ruminal fluid may be as great as 10:1. Bacterial
      survival appears to be at least partially explained by the method of sugar
      transport. When bacteria rely solely on mechanisms of ion-coupled sugar symport,
      an energized membrane is necessary for the reinitiation of growth. If group
      translocation (phosphotransferase system) is the mechanisms of transport, uptake
      can be driven by phosphoenolpyruvate, and an energized membrane and the storage
      of intracellular reserve materials are not an absolute criteria for survival. In
      some cases, N deprivation accelerates death. When Prevotella ruminicola was
      limited for N under conditions of excess energy, methylglyoxal production caused
      a rapid decrease in viability. The impact of bacterial death in the rumen is not
      clear-cut. If the rate of fermentation is zero-order with respect to cell
      concentration (substrate-limited), cell death would have little impact on
      digestion.

PMID- 8880475
TI  - Why don't ruminal bacteria digest cellulose faster?
AB  - The bacteria Fibrobacter succinogenes, Ruminococcus flavefaciens, and
      Ruminococcus albus generally are regarded as the predominant cellulolytic
      microbes in the rumen. Comparison of available data from the literature reveals
      that these bacteria are the most actively cellulolytic of all mesophilic
      organisms described to date from any habitat. In light of numerous proposals to
      improve microbial cellulose digestion in ruminants, it is instructive to examine
      the characteristics of these species that contribute to their superior
      cellulolytic capabilities and to identify the factors that prevent them from
      digesting cellulose even more rapidly. As a group, these species have extreme
      nutritional specialization. They are able to utilize cellulose (or in some cases
      xylan) and its hydrolytic products as their nearly sole energy sources for
      growth. Moreover, each species apparently has evolved to similar maximum rates of
      cellulose digestion (first-order rate constants of 0.05 to 0.08 h-1). Active
      cellulose digestion involves adherence of cells to the fibers via a glycoprotein
      glycocalyx, which protects cells from protozoal grazing and cellulolytic enzymes
      from degradation by ruminal proteases while it retains-at least temporarily-the
      cellodextrin products for use by the cellulolytic bacteria. These properties
      result in different ecological roles for the adherent and nonadherent populations
      of each species, but overall provide an enormous selective advantage to these
      cellulolytic bacteria in the ruminal environment. However, major constraints to
      cellulose digestion are caused by cell-wall structure of the plant (matrix
      interactions among wall biopolymers and low substrate surface area) and by
      limited penetration of the nonmotile cellulolytic microbes into the cell lumen.
      Because of these constraints and the highly adapted nature of cellulose digestion
      by the predominant cellulolytic bacteria in the rumen, transfer of cellulolytic
      capabilities to noncellulolytic ruminal bacteria (e.g., by genetic engineering)
      that display other desirable properties offers limited opportunities to improve
      ruminal digestion of cellulose.

PMID- 8880476
TI  - Why are ruminal cellulolytic bacteria unable to digest cellulose at low pH?
AB  - Ruminant animals depend on cellulolytic ruminal bacteria to digest cellulose, but
      these bacteria cannot resist the low ruminal pH that modern feeding practices can
      create. Because the cellulolytic bacteria cannot grow on cellobiose at low pH, pH
      sensitivity is a general aspect of growth and not just a limitation of the
      cellulases per se. Acid-resistant ruminal bacteria have evolved the capacity to
      let their intracellular pH decrease, maintain a small pH gradient across the cell
      membrane, and prevent an intracellular accumulation of VFA anions. Cellulolytic
      bacteria cannot grow with a low intracellular pH, and an increase in pH gradient
      leads to anion toxicity. Prevotella ruminicola cannot digest native cellulose,
      but it grows at low pH and degrades the cellulose derivative,
      carboxymethylcellulose. The Prevotella ruminicola carboxymethylcellulase cannot
      bind to cellulose, but a recombinant enzyme having the Prevotella ruminicola
      catalytic domain and a binding domain from Thermomonspora fusca was able to bind
      and had cellulase activity that was at least 10-fold higher. Based on these
      results, gene reconstruction offers a means of converting Prevotella ruminicola
      into a ruminal bacterium that can digest cellulose at low pH.

PMID- 8880477
TI  - New laboratory guidelines for serologic diagnosis of Lyme disease: evaluation of
      the two-test protocol.
AB  - Recent guidelines established by the Association of State and Territorial Public
      Health Laboratory Directors (ASTPHLD) and the U.S. Centers for Disease Control
      and Prevention (CDC) recommend the use of a two-test protocol for the serologic
      diagnosis of Lyme disease (LD). The two-test protocol relies on a sensitive
      screening test, which is followed by specific immunoglobulin M (IgM) and/or IgG
      immunoblotting (IB), depending on the date of disease onset, of all samples with
      equivocal and positive screening test results. We evaluated a commercially
      available IgM-IgG enzyme-linked immunosorbent assay (ELISA) and separate IB tests
      for IgM and IgG antibodies to Borrelia burgdorferi as candidate assays for the
      two-test protocol. Serum samples obtained from healthy controls (n = 29), from
      patients with diagnoses or laboratory findings associated with serologic cross
      reactivity to LD (n = 24), and from patients with well-documented early- and late
      stage LD provided by the CDC and the College of American Pathologists (n = 53)
      were examined to determine each assay's individual sensitivity and specificity.
      No false-positive results were detected among the healthy controls by either
      ELISA or IB, whereas four false-positive ELISA results were recorded within the
      cross-reactive group. None of these sera, however, were positive for either IgM
      or IgG reactivity according to IB band criteria. With regard to the patients with
      LD, we determined the sensitivity and specificity of the ELISA to be 96 and 100%,
      respectively, compared with the reference data provided for these specimens. When
      we compared our IB results with data from CDC, the assay sensitivity and
      specificity were 80 and 96.2%, respectively, for IgM and 81.8 and 95.8%,
      respectively, for IgG. Pursuant to this evaluation we assessed the suitability of
      the two-test protocol by performing a retrospective analysis using clinical
      history to define samples as positive or negative for LD. We determined clinical
      sensitivity and specificity for all study subjects (n = 112) to be 50 and 100%,
      respectively. A reduction in the clinical sensitivity of the two-test protocol
      was associated with a lack of antibody response or seroconversion in LD patients
      treated with antibiotics. We conclude that the CDC-ASTPHLD guidelines provide
      useful criteria for test performance and interpretation aimed at standardizing
      the serologic diagnosis of LD.

PMID- 8880478
TI  - Detection and identification of mycobacteria in formalin-fixed, paraffin-embedded
      tissues by nested PCR and restriction enzyme analysis.
AB  - A novel assay based on a nested PCR and restriction enzyme analysis of the PCR
      products was developed for the rapid detection and identification of
      Mycobacterium bovis and M. avium-M. intracellulare species in formalin-fixed,
      paraffin-embedded tissue (PET) specimens. On the basis of the nucleotide sequence
      data obtained in the present study, general nested primers were constructed to
      amplify a 424-bp segment of the gene encoding the 65-kDa surface antigen of
      mycobacteria. The nested PCR assay proved to be highly sensitive, since as little
      as 5 to 10 fg of extracted mycobacterial DNA was detected. The safety of the
      assay as a routine method for the diagnosis of M. bovis and M. avium-M.
      intracellulare in PET specimens was provided by taking various precautions. In
      order to prevent false positivity, specific tools and procedures were applied. To
      detect false-negative results and assess the efficiency of the PCR, an internal
      standard molecule of amplification was constructed. The digestion of the
      amplicons with the restriction endonuclease Sau96-I allowed the identification of
      M. bovis and M. avium-M. intracellulare in a large number of clinical specimens.
      The present results indicate that PCR combined with an internal control of
      amplification and restriction enzyme analysis of the amplicons provides a rapid,
      sensitive, and reliable method for routine diagnostic laboratories to detect and
      identify M. bovis and M. avium-M. intracellulare in PET specimens.

PMID- 8880479
TI  - Isolation of Arthrobacter spp. from clinical specimens and description of
      Arthrobacter cumminsii sp. nov. and Arthrobacter woluwensis sp. nov.
AB  - Arthrobacter spp. are very widely distributed in the environment (e.g., soil) but
      have not been described as causing disease in humans. Over a 6-year period, two
      reference laboratories isolated or received 11 strains which were eventually
      identified as belonging to the genus Arthrobacter. These strains had been
      initially identified as Centers for Disease Control and Prevention coryneform
      group B-1 and B-3 bacteria (whitishgrayish colonies of 2 mm or greater in
      diameter after 24 h of incubation, respiratory metabolism, absent or weak acid
      production from sugars, and hydrolysis of gelatin). However, chemotaxonomic
      investigations revealed lysine as the diamino acid of the cell wall and the
      presence of branched cellular fatty acids (with anteiso-pentadecanoic acid
      predominating) which was compatible with an assignment of the 11 isolates to the
      genus Arthrobacter only. Peptidoglycan and 16S rRNA gene sequence analyses
      demonstrated that three of the strains studied were representatives of a new
      Arthrobacter species for which the name Arthrobacter cumminsii sp. nov. is
      proposed and that one other strain represented a second new Arthrobacter species
      for which the name Arthrobacter woluwensis sp. nov. is proposed. This report is
      the first on the isolation of Arthrobacter spp. from clinical specimens.

PMID- 8880480
TI  - Enterohemolytic phenotypes and genotypes of shiga toxin-producing Escherichia
      coli O111 strains from patients with diarrhea and hemolytic-uremic syndrome.
AB  - Thirty-six Shiga toxin-producing Escherichia coli (STEC) O111:H- strains, 18 of
      which were isolated from patients with hemolytic-uremic syndrome (HUS) and 18
      from patients suffering from diarrhea, were investigated for their
      enterohemolytic phenotypes and genotypes. Twenty-two strains were EHEC hemolysin
      (EHEC Hly) positive by probe hybridization and by PCR with sequences
      complementary to the EHEC hlyA gene of E. coli O157:H7, but only 20 of these were
      hemolytic on blood agar plates. The remaining 14 strains were EHEC Hly negative
      according to DNA-based methods and did not express the enterohemolytic phenotype.
      The enterohemolytic phenotype was observed in 16 of 18 (88%) strains from
      patients with HUS but only in 4 of 18 (22.2%) of the STEC O111:H- strains from
      patients with diarrhea. All STEC O111:H- strains carried large plasmids, as shown
      by plasmid analysis, but only plasmids of EHEC Hly probe-positive strains
      hybridized with the CVD419 probe. A BamHI fragment of approximately 12 kb was
      cloned from the large plasmid of the E. coli O111:H- strain 78/92 and shown to
      mediate hemolytic activity when transformed into the E. coli laboratory strain
      HB101. The EHEC O111 hlyA gene was sequenced completely and shown to have 99.4%
      sequence identity to the corresponding EHEC O157 hlyA gene of the E. coli O157:H7
      strain EDL 933. Our results indicate that detection of EHEC Hly either by DNA
      based methods or by investigation of the enterohemolytic phenotype on blood agar
      alone is insufficient for screening STEC O111 strains. However, the high
      incidence of EHEC Hly in isolates from patients with HUS and its rare occurrence
      in isolates from patients with diarrhea may indicate that STEC O111 strains have
      a distinct pathogenic potential for humans and that the presence of EHEC Hly
      increases the ability of an STEC O111 strain to cause extraintestinal
      complications in humans.

PMID- 8880481
TI  - Urine sample used for congenital toxoplasmosis diagnosis by PCR.
AB  - The diagnosis of toxoplasmosis in congenitally infected infants can be difficult;
      serology is unreliable, and diagnosis must be based on the combination of
      symptomatology and direct demonstration of the parasite. Four infants suspected
      of having Toxoplasma gondii infection were studied by serological analysis,
      tissue culture, and PCR determination. T. gondii was isolated from the urine of
      one patient. The parasite was detected by PCR in the blood and cerebrospinal
      fluid of three infants and in the urine in all patients. Because nested PCR
      proved to be a sensitive, relatively rapid, and specific method and because it
      can be applied to a variety of different clinical samples, PCR can be a valuable
      technique for the identification of T. gondii infections in children. The present
      study indicates that PCR examination of urine, a fluid never before used for
      diagnosis in this age group, may be valuable in diagnosing cases of congenital
      toxoplasmosis.

PMID- 8880482
TI  - Genotyping hepatitis C virus isolates from Spain, Brazil, China, and Macau by a
      simplified PCR method.
AB  - An improved and simplified method of genotyping was developed for classifying
      hepatitis C virus (HCV) isolates into the five common genotypes, i.e., I/1a,
      II/1b, III/2a, IV/2b, and V/3a, by PCR with genotype-specific primers deduced
      from the core gene. Sense and antisense primers, specific for each of the five
      common genotypes, were designed by comparison of 319 core gene sequences from HCV
      isolates of various genotypes from genetic groups 1 to 9. In the first round of
      PCR, a sequence of 433 bp representing nucleotides 319 to 751 was amplified with
      universal primers. The second round of PCR was performed with respective sense
      and antisense primers in two separate reactions, one for the amplification of
      genotypes I/1a and II/1b and the other for the amplification of genotypes III/2a,
      IV/2b, and V/3a. The specificity of genotyping was confirmed with a panel of 191
      serum samples containing HCV isolates whose core gene sequences were known: 110
      serum samples infected with HCV of the five common genotypes and 81 serum samples
      infected with HCV of other genotypes. The use of sense and antisense primers for
      genotype II/1b (primers 389 and 492) abolished the cross-reaction of the
      antisense primer for genotype II/1b (primer 133) with some HCV isolates of
      genotype I/1a found by our original method. The new method was used for
      genotyping 130 HCV isolates from Spain, 53 from Brazil, 106 from China, and 30
      from Macau. A total of 329 bp of the NS5b region (nucleotides 8279 to 8607) of
      five isolates from Spain and five isolates from Macau which could not be
      classified as any of the five common HCV genotypes or genotype 2c were sequenced,
      and the sequences were compared with those of HCV isolates of known genotypes;
      two isolates from Spain were deduced to be of genotype 4d and one was deduced to
      be of genotype 1d, while the remaining two isolates from Spain had novel
      genotypes in genetic group 2; however, all five isolates from Macau were of
      genotype 6a.

PMID- 8880483
TI  - Effect of hydrocortisone succinate on growth of Chlamydia pneumoniae in vitro.
AB  - We examined the effect of hydrocortisone succinate on the growth of three
      isolates of Chlamydia pneumoniae in vitro. There was a significant increase in
      the number of inclusions seen in two of the C. pneumoniae strains in the presence
      of hydrocortisone. There was no significant increase in the number of inclusions
      with various concentrations of hydrocortisone over time. The addition of
      hydrocortisone did not affect the in vitro activities of azithromycin,
      erythromycin, and doxycycline against C. pneumoniae.

PMID- 8880485
TI  - DNA fingerprinting by infrequent-restriction-site amplification.
AB  - Identification of bacterial strains by DNA fingerprinting facilitates
      epidemiologic studies and improves disease control. For some species of
      organisms, no typing method is available; for others, typing methods are tedious.
      We developed a method of amplifying DNA sequences flanking infrequent restriction
      sites by PCR and used the method to produce strain-specific electrophoretic
      patterns from crude bacterial lysates. This method of fingerprinting is rapid,
      sensitive, and widely applicable. Identical enzymes, adaptors, primers, and PCR
      conditions were used to characterize 32 Mycobacterium avium-M. intracellulare
      isolates, 4 Pseudomonas aeruginosa isolates, and 4 Staphylococcus aureus
      isolates.

PMID- 8880484
TI  - Discordant results from hepatitis C virus genotyping by procedures based on
      amplification of different genomic regions.
AB  - We compared the results of genotyping hepatitis C virus (HCV) either by PCR
      amplification of the core region or by hybridization of PCR-amplified products of
      the 5' untranslated region (5'UTR assay). Serum samples from 144 Italian anti-HCV
      positive patients (106 drug abusers and 38 patients with chronic viral liver
      disease but no history of drug abuse) were studied. The original core region
      assay described by Okamoto et al. (H. Y. Okamoto, Y. Sugiyama, S. Okada, K.
      Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyakawa, and M.
      Mayumi, J. Gen. Virol. 73:673-679, 1992) allowed genotyping of 75 of 144 samples.
      A modified version of Widell et al. (A. Widell, S. Shev, S. Mansson, Y.-Y. Zhang,
      U. Foberg, G. Norkrans, A. Fryden, O. Weiland, J. Kurkus, and E. Nordenfelt, J.
      Med. Virol. 44:272-279, 1994) allowed genotyping of 11 of 79 samples (50 of 79
      samples remained unclassified by the method of Okamoto et al. In contrast, all
      144 samples were genotyped by the 5'UTR assay. Forty-six of 75 (61 percent) of
      the samples genotyped by the method of Okamoto et al. and 10 of 11 (91 percent)
      of the samples genotyped by the method of Widell et al. had results consistent
      with those obtained by the 5'UTR assay. According to the results of direct
      sequencing, the method of Okamoto et al. erroneously classified seven samples as
      having mixed infections. In conclusion, HCV genotyping seems more reliable when
      it is performed by the 5'UTR assay than by either of two core region assays. The
      major advantage provided by the 5'UTR assay is a much lower proportion of
      negative or indeterminate results in younger patients with histories of drug
      abuse or infection by genotypes other than HCV type 1.

PMID- 8880486
TI  - Comparison of fluorescent BACTEC 9000 MB system, Septi-Chek AFB system, and
      Lowenstein-Jensen medium for detection of mycobacteria.
AB  - The newly developed fluorescent BACTEC 9000 MB system for automated culture of
      mycobacteria was compared with the Septi-Chek AFB system and Lowenstein-Jensen
      medium (LJ). A total of 2,005 clinical specimens were included in the study.
      Mycobacteria were isolated from 202 (10.1%) specimens, including 155
      Mycobacterium tuberculosis complex isolates and 47 Mycobacteria other than M.
      tuberculosis isolates. Of 131 isolates detected by the BACTEC system, the Septi
      Chek AFB system, or both, 120 (91.6%) were detected by the BACTEC system and 105
      (80.2%) were detected by the Septi-Chek AFB system (P < 0.02). The recovery rate
      in the BACTEC system compared with that in the Septi-Chek AFB system was
      significantly higher for M. tuberculosis complex isolates (P < 0.005) and for
      isolates from acid-fast smear-negative specimens (P < 0.01). Of 148 isolates
      detected by the BACTEC system, LJ, or both, 142 (95.9%) were detected by the
      BACTEC system and 118 (79.9%) were detected by LJ (P < 0.001). The recovery rate
      in the BACTEC system compared with that on LJ was significantly higher for M.
      tuberculosis complex isolates (P < 0.001). The BACTEC system detected more
      mycobacteria from both smear-positive and smear-negative specimens than LJ. The
      mean times to detection of mycobacteria were 17.6 days for the BACTEC system,
      26.0 days for the Septi-Chek AFB system, and 29.4 days for LJ. The BACTEC
      fluorescent 9000 MB system is a rapid, sensitive, and efficient method for the
      isolation of mycobacteria.

PMID- 8880487
TI  - Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by ligase chain
      reaction-based assays with clinical specimens from various sites: implications
      for diagnostic testing and screening.
AB  - Ligase chain reaction (LCR)-based tests for the diagnosis of Chlamydia
      trachomatis and Neisseria gonorrhoeae infections in men and women attending a
      sexually transmitted disease clinic were evaluated. LCR testing of urethral swab
      and urine specimens from men and cervical swab and urine specimens from women was
      compared with culture of male urethral swabs and female cervical and urethral
      swabs, respectively. An expanded "gold standard" was defined as a positive
      culture or at least one specimen confirmed to be positive by LCR testing. The
      prevalence of C. trachomatis infection as detected by cell culture was 7.0% among
      614 men and 5.0% among 602 women. By LCR, these values increased to 11.4 and 9.9%
      with urethral swabs and urine, respectively, for men and 9.6 and 9.1% with
      cervical swabs and urine, respectively, for women. Relative to the expanded gold
      standard, the sensitivity of cell culture with male urethral swabs or female
      cervical swabs was 57.3 and 45.5%, respectively, compared with corresponding
      values of 93.3 and 87.9% for LCR. The sensitivity of LCR with urine specimens was
      77.3 and 78.8% for men and women, respectively. The prevalence of N. gonorrhoeae
      infection as detected by culture was 5.9% among 220 men and 2.9% among 383 women.
      The corresponding values were 8.2 and 5.5%, respectively, by LCR testing of
      swabs. Prevalence values by LCR testing of urine were 7.3% for men and 2.9% for
      women. The sensitivity of culture was 72.2% for men and 50.0% for women. The
      sensitivities of LCR were 100% with male urethral swabs, 95.4% with female
      cervical swabs, 88.9% with male urine, and 50.0% with female urine. These results
      indicate that the LCR-based assays represent a major improvement in C.
      trachomatis and N. gonorrhoeae diagnostics. The sensitivity of testing of
      urethral or cervical swabs by LCR was markedly greater than that by culture. The
      sensitivity of testing female or male urine specimens was equal to or greater
      than that of culturing cervical or urethral specimens. LCR testing of urine
      specimens may prove useful for screening for C. trachomatis.

PMID- 8880489
TI  - Evaluation of the Microbial Identification System for identification of
      clinically isolated yeasts.
AB  - The Microbial Identification System (MIS; Microbial ID, Inc., Newark, Del.) was
      evaluated for the identification of 550 clinically isolated yeasts. The organisms
      evaluated were fresh clinical isolates identified by methods routinely used in
      our laboratory (API 20C and conventional methods) and included Candida albicans
      (n = 294), C. glabrata (n = 145), C. tropicalis (n = 58), C. parapsilosis (n =
      33), and other yeasts (n = 20). In preparation for fatty acid analysis, yeasts
      were inoculated onto Sabouraud dextrose agar and incubated at 28 degrees C for 24
      h. Yeasts were harvested, saponified, derivatized, and extracted, and fatty acid
      analysis was performed according to the manufacturer's instructions. Fatty acid
      profiles were analyzed, and computer identifications were made with the Yeast
      Clinical Library (database version 3.8). Of the 550 isolates tested, 374 (68.0%)
      were correctly identified to the species level, with 87 (15.8%) being incorrectly
      identified and 89 (16.2%) giving no identification. Repeat testing of isolates
      giving no identification resulted in an additional 18 isolates being correctly
      identified. This gave the MIS an overall identification rate of 71.3%. The most
      frequently misidentified yeast was C. glabrata, which was identified as
      Saccharomyces cerevisiae 32.4% of the time. On the basis of these results, the
      MIS, with its current database, does not appear suitable for the routine
      identification of clinically important yeasts.

PMID- 8880488
TI  - Detection of Trypanosoma brucei spp. in human blood by a nonradioactive branched
      DNA-based technique.
AB  - We have developed a nonradioactive branched DNA (bDNA)-based assay for the
      diagnosis of the African trypanosomiases in simple buffy coat preparations of
      human blood. Two repetitive DNA sequences specific to the Trypanosoma brucei
      complex were chosen as targets of the bDNA assay, a technique which amplifies the
      signal from a target molecule rather than the target itself. Comparable
      sensitivities were observed with cloned target sequences, purified T. brucei DNA,
      procyclic trypanosomes, and bloodstream trypomastigotes. The results of bDNA
      analysis of human blood samples from Cote d'Ivoire (n = 50) showed excellent
      agreement with those of buffy coat microscopy. The bDNA technology offers certain
      advantages over alternative molecular biological techniques, including the
      simplicity of sample preparation and of the procedure itself, the stability of
      the reagents, the ability to process large numbers of samples simultaneously, and
      freedom from crosscontamination artifacts. We have successfully applied the bDNA
      technique to the detection of T. brucei in clinical samples from regions where T.
      brucei infection is endemic; to our knowledge, this is the first report of the
      molecular detection of T. brucei in human blood.

PMID- 8880490
TI  - Serodiagnosis of Porphyromonas gingivalis infection by immunoblot analysis with
      recombinant collagenase.
AB  - The Porphyromonas gingivalis collagenase-specific serum immunoglobulin A (IgA),
      IgM, and IgG responses from 20 patients with early-onset periodontitis (EOP), 20
      patients with adult periodontitis, (AP), and 20 age- and sex-matched healthy
      controls were examined by immunoblot analysis. A recombinant collagenase antigen
      used for the immunoblot analysis was produced by using the plasmid pGEX-2T, which
      allows the fusion between the collagenase and glutathione S-transferase. There
      was no significant difference in collagenase-specific IgG antibody detection
      between samples from the EOP, AP, and control groups. In contrast, 85% of AP and
      EOP sera had collagenase-specific IgA antibodies, whereas only 20% of control
      sera showed collagenase-specific IgA reactivity. Plaque samples from all groups
      were assessed by PCR with primers complementary to the collagenase-encoding gene
      prtC. The results indicated that 90% of AP and EOP plaque samples and 10% of
      control samples were positive for P. gingivalis. All patients with collagenase
      specific IgA antibodies were PCR positive. The results of the study indicate a
      nearly complete concordance (k = 0.856) between the presence of collagenase
      specific IgA antibodies and PCR detection of P. gingivalis. By using PCR as the
      "gold standard," the sensitivity and specificity of the IgA immunoblot test were
      94.7 and 90.9%, respectively. Therefore, the recombinant collagenase is a
      potential candidate for use in the serodiagnosis of periodontitis.

PMID- 8880491
TI  - Acinetobacter species identification by using tRNA spacer fingerprinting.
AB  - Identification of Acinetobacter spp. to the DNA group level by phenotypic
      techniques is problematic, and there is a need for an alternative identification
      method for routine use. The present study validated the suitability of a rapid
      identification technique based on tRNA spacer (tDNA) fingerprinting in comparison
      with that of a commercially available assay involving carbon source utilization
      tests (Biolog MicroStation System) for identifying the 21 DNA-DNA hybridization
      groups belonging to the genus. For this purpose, 128 strains identified
      previously by DNA-DNA hybridization were analyzed by both techniques. tDNA
      fingerprinting was highly reproducible and classified all strains into 17 groups.
      Six DNA groups belonging to the A. calcoaceticus-A. baumannii complex were
      grouped into two distinct clusters, indicating the high degree of genetic
      similarity within this complex. Strains of the more recently described DNA groups
      BJ13 to BJ16 were ambiguously grouped and displayed three pattern types. The
      software used with the commercial carbon source utilization method grouped the
      128 strains into 12 clusters, explaining the less discriminatory power of this
      system. We conclude that tDNA fingerprinting offers a quick and reliable method
      for the routine differentiation of most Acinetobacter spp. at the subgenus level.

PMID- 8880492
TI  - Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR
      using synthetic DNA fragments.
AB  - Helicobacter pylori is closely related to upper gastrointestinal diseases, and
      the precise evaluation of H. pylori infection is necessary for the treatment of
      these diseases. The aim of the present study was to establish a method for the
      quantitative detection of H. pylori. We applied a competitive PCR method using
      various amounts of synthetic DNA fragments containing the same primer-binding and
      a subset of the same template sequences as the target competing for primer
      binding and amplification in order to quantify H. pylori in gastric mucus. The
      results obtained by this method were compared with the results of histological
      examination, the rapid urease test, bacterial culture, the [13C]urea breath test,
      and urea and ammonia measurements in gastric juice. As the quantity of H. pylori
      in gastric mucus increased, the rates of positivity of histological examination,
      the rapid urease test, and bacterial culture increased. The quantity of H. pylori
      in gastric mucus was also significantly correlated with the results of the
      [13C]urea breath test and was negatively correlated with the urea/ammonia ratio
      in gastric juice. The competitive PCR method provides an objective measure of the
      quantity of H. pylori and makes it possible to distinguish true negatives from
      false negatives due to incomplete PCR and true positives from false positives due
      to contamination. This method is very useful for the precise evaluation of
      gastric H. pylori infection.

PMID- 8880493
TI  - Haemophilus influenzae adherent to contact lenses associated with production of
      acute ocular inflammation.
AB  - Ten episodes of adverse responses to contact lens wear, including contact lens
      induced acute red eye (CLARE), in which Haemophilus influenzae was isolated from
      contact lenses and/or from one of the external ocular sites at the time of the
      event, are described. All episodes occurred in patients wearing disposable
      hydrogel lenses on a 6-night extended-wear schedule. Two of the patients had
      recurrent episodes. H. influenzae was usually isolated in large numbers, and
      other bacteria or fungi colonizing the contact lens or the external ocular
      surface were usually present in low numbers. Those patients who were colonized
      with H. influenzae were more than 100 times as likely to have had a CLARE or
      infiltrative response than those subjects who were not colonized with this
      bacterium. H. influenzae colonization of the contact lens and eye may be
      subsequent to colonization of the nasopharynx because four of the seven patients
      presented with fever at the time of the event, with concurrent upper respiratory
      tract infection. Contact lens wearers should be made aware of the potential risk
      of CLARE associated with the wearing of contact lenses for extended periods
      during and subsequent to upper respiratory tract infection.

PMID- 8880494
TI  - Encephalopathy associated with enteroinvasive Escherichia coli 0144:NM infection.
AB  - Central nervous system manifestations typically occur with Shigella
      gastroenteritis and also in enteric Salmonella and Campylobacter infections. To
      date no association between enteroinvasive Escherichia coli infection and
      neurologic symptoms has been described. Two children with diarrhea caused by E.
      coli 0144:NM had otherwise unexplained encephalopathy manifested by profound
      stupor in one child and by obtundation and meningismus in the other one. These
      cases of infection occurred in northern Israel during a period of an unusually
      high rate of enteric infection caused by this organism. None of the microbiologic
      properties studied were uniquely attributable to the encephalopathic cases. The
      two encephalopathic as well as all eight nonencephalopathic isolates studied
      possessed the 140-MDa invasive plasmid. All 10 isolates examined produced small
      amounts of cytotoxin by the HeLa cell assay, all were nonmotile, and all had
      identical antibiograms. Eight of 10 of the isolates had identical plasmid
      profiles, while 2 isolates (from nonencephalopathic patients) had slightly
      different plasmid profiles. This is the first report of encephalopathy associated
      with enteroinvasive E. coli.

PMID- 8880495
TI  - Alkaline decontamination of sputum specimens adversely affects stability of
      mycobacterial mRNA.
AB  - Reverse transcriptase PCR (RT-PCR) is an important tool for Mycobacterium
      tuberculosis research and diagnostics. A standard procedure using N-acetyl-L
      cysteine (NALC) and NaOH has been widely adopted for digestion and
      decontamination of sputum specimens for mycobacterial culture. The objective of
      this study was to determine the compatibility of this method with the recovery of
      RNA for RT-PCR assays. Nineteen sputum specimens were collected from smear
      positive, pretreatment tuberculosis patients. After homogenization with NALC and
      glass beads, specimens were further processed by the addition of either NaOH, as
      per the standard decontamination protocol, or phosphate buffer. RNA was prepared
      by using a modified guanidine-phenol extraction method developed specifically for
      sputum sediments. DNA was isolated from the same specimens. Reverse
      transcriptions of alpha antigen (85B protein) mRNA and 16S rRNA were performed
      together, and aliquots were removed for separate PCRs. In all specimens, the 85B
      mRNA target was greatly diminished by treatment with NaOH; however, the 16S rRNA
      target remained unaffected. Storing sputum specimens for 48 h at 4 degrees C
      before processing did not seem to affect the integrity or yield of RNA; however,
      some degradation occurred by 72 h. Data suggest that the NaOH-NALC method for
      processing sputum samples is not suitable for detecting mRNA targets in RT-PCR
      assays.

PMID- 8880496
TI  - PCR ribotyping for characterizing Salmonella isolates of different serotypes.
AB  - The 16S-23S intergenic spacer region in 218 strains of Salmonella isolated from
      four Italian hospitals during the period from 1977 to 1994 was analyzed by PCR
      ribotyping. This molecular typing technique allowed for the identification of
      seven different and specific electrophoretic profiles for the seven serovars S:
      enteritidis, S. london, S. anatum, S. panama, S. heidelberg, S. agona, and S.
      goldcoast. Otherwise, the spacer region appears to be polymorphic in S.
      typhimurium S. infantis, and S. derby since we could identify eight, six, and
      four different ribotypes, respectively.

PMID- 8880497
TI  - Evaluation of an extended blood culture protocol to isolate fastidious organisms
      from patients with AIDS.
AB  - Recent reports of fastidious pathogens suggest the need for special blood
      cultures for immunocompromised patients. Blood cultures from 45 human
      immunodeficiency virus (HIV)-infected patients with unexplained fever (> or =
      38.0 degrees C) and CD4 counts of < 125 cells per mm3 were collected into a
      vacuum tube with sodium polyanetholsulfonate, an Isolator tube, and BACTEC
      aerobic and anaerobic bottles. Blood from the sodium polyanethosulfonate tube was
      inoculated into BACTEC 13A bottles, which were read weekly for 16 weeks. Isolator
      sediment was divided among eight agar media, including four sheep blood agar
      media: chocolate agar, brain heart infusion blood agar, heart infusion blood
      agar, and brucella blood agar. Other agar plates included Sabouraud's, buffered
      charcoal-yeast extract, Middlebrook 7H11 (M7H11) with hemoglobin, and M7H11 with
      mycobactin J. Incubation conditions included air and CO2-enriched aerobic,
      microaerophilic, and anaerobic atmospheres. Aerobic BACTEC broths received an
      acridine orange stain on day 8 and were subcultured at 2, 4, and 8 weeks.
      Anaerobic BACTEC bottles were subcultured at 4 weeks. All solid media, including
      subcultures, were incubated for 8 weeks, providing a total of 16 weeks of
      incubation for each specimen. Clinically significant isolates included eight
      Mycobacterium avium complex isolates and one each of Bartonella henselae,
      Bartonella quintana, Shigella flexneri, Klebsiella oxytoca, and Cryptococcus
      neoformans. All isolates were detected with commercially available media and,
      with the exception of Bartonella spp., were recovered within incubation times
      routinely used in most clinical laboratories.

PMID- 8880499
TI  - Direct identification and typing of Mycobacterium tuberculosis by PCR.
AB  - We have developed a rapid PCR assay that types strains of Mycobacterium
      tuberculosis by generating distinct DNA fingerprints directly from primary
      cultures. This assay allows strain identification analogous to that achieved by
      the standard restriction fragment length polymorphism method, and fingerprints
      are obtained in less than 8 h. This assay does not require subculturing, DNA
      purification, restriction digestion, Southern blotting, or nucleic acid
      hybridization. Rapid and precise identification of M. tuberculosis strains
      permits immediate molecular epidemiologic studies. The assay can be converted to
      a computer-automated system by employing fluorescently labeled PCR primers and
      the Perkin-Elmer DNA sequencer so that unknown-specimen fingerprints are
      identified by computer comparison to a database of M. tuberculosis strain
      fingerprints.

PMID- 8880498
TI  - Comparison of pulsed-field gel electrophoresis and randomly amplified DNA
      polymorphism analysis for typing extended-spectrum-beta-lactamase-producing
      Klebsiella pneumoniae.
AB  - The incidence and transmission patterns of extended-spectrum-beta-lactamase
      (ESBL)-producing Klebsiella pneumoniae in patients admitted to the intensive care
      unit (ICU) of a university hospital were investigated over a 3-year period. K.
      pneumoniae isolates were characterized by antibiotic susceptibility, capsular
      serotyping, plasmid profiles, and pulsed-field gel electrophoresis (PFGE) of
      genome macrorestriction patterns with XbaI, and the results were compared with
      those obtained by typing with the randomly amplified polymorphic DNA (RAPD)
      patterns. The discriminatory power of RAPD typing was evaluated for three
      primers. The incidence of isolation of ESBL-producing K. pneumoniae was 2.5 cases
      per 1,000 admissions to the ICU versus 0.35 cases per 1,000 admissions to other
      units (relative risk, 7.03; 95% confidence interval, 3.89 to 12.69). Infection
      developed in 53% of evaluable patients. Thirty-six percent of the cases were
      possibly acquired in other institutions. Isolates from ICU patients were
      subdivided into six capsular serotypes and into four clonal groups based on
      antibiotype, plasmid content, and PFGE and RAPD patterns. Two clones were
      associated with clusters of cross-infection, involving 5 and 12 patients,
      respectively. Following implementation of contact isolation precautions, the
      incidence of nosocomial acquisition of ESBL-producing K. pneumoniae decreased
      from 0.55 to 0.26 cases per 1,000 admissions (P = 0.03). PFGE and RAPD analysis
      showed concordant results and comparable discrimination for differentiation
      between groups of epidemiologically related strains of ESBL-producing K.
      pneumoniae. More subclonal variants were determined among epidemic clones by PFGE
      analysis than by RAPD analysis. Both methods are useful for typing K. pneumoniae
      strains in epidemiological investigations, although RAPD analysis is more
      efficient.

PMID- 8880500
TI  - Molecular characterization of Salmonella enterica subsp. enterica serovar
      choleraesuis field isolates and differentiation from homologous live vaccine
      strains suisaloral and SC-54.
AB  - Four independent molecular methods were used to characterize the Salmonella
      enterica subsp. enterica serovar choleraesuis live vaccine strains SC-54 and
      Suisaloral and to differentiate them from S. choleraesuis field isolates. Plasmid
      analysis revealed the presence of seven plasmid profiles. A virulence plasmid of
      52-kbp was identified by hybridization with an spvB-spvC gene probe in each of
      the S. choleraesuis field isolates and in the Suisaloral vaccine strain, but not
      in the SC-54 vaccine strain. Ribotyping, performed with a gene probe that
      recognized 23S, 16S, and 5S rRNA genes, resulted in three closely related
      hybridization patterns. IS200 elements were not detected in the field isolates or
      in the two S. choleraesuis live vaccine strains. Macrorestriction analysis with
      the enzymes XbaI, SpeI, NotI, and SfiI differentiated the 29 S. choleraesuis
      strains included in this study into 10, 13, 8, and 13 different fragment
      patterns, respectively. While the Suisaloral vaccine strain showed a unique XbaI
      macrorestriction pattern, the fragment patterns of the SC-54 strain obtained with
      the different enzymes were shared by 2 to 18 S. choleraesuis field strains. A
      combination of plasmid analysis and macrorestriction analysis proved to be most
      suitable for the molecular typing of S. choleraesuis and the differentiation of
      both live vaccine strains from field isolates of this serovar.

PMID- 8880501
TI  - PCR detection of DNA specific for Aspergillus species in serum of patients with
      invasive aspergillosis.
AB  - We investigated the possible presence of DNA specific for Aspergillus species in
      serum samples of patients with invasive aspergillosis (IA) by the nested PCR
      method. Fourteen strains of fungi including 5 strains of Aspergillus species and
      10 strains of common bacteria were used for examination of specificity and
      sensitivity of the nested PCR. Two sets of oligonucleotide primers were derived
      from the sequence of the variable regions V7 to V9 of the 18S rRNA genes of
      Aspergillus fumigatus. The specific fragment was amplified from five strains of
      Aspergillus species in the single and nested PCR but not from other
      microorganisms. Target DNA was detected by the nested PCR with as little as 50 fg
      of the extracted DNA of A. fumigatus. We investigated the detection of DNA
      specific for Aspergillus species in serum samples of a murine model of
      aspergillosis and 20 patients with IA. The specific fragment was detected by the
      nested PCR in 71% of serum samples of infected mice and 70% of serum samples of
      patients with IA, while galactomannan antigen was detected in 43 and 60% of
      samples, respectively. The high sensitivity and specificity of the nested PCR
      indicate that the assay can provide early diagnosis with sufficient accuracy to
      be clinically useful for immunocompromised patients with IA.

PMID- 8880502
TI  - Differentiation of Mycobacterium bovis isolates from animals by DNA typing.
AB  - The insertion sequence IS6110 and the direct repeat (DR) specific to tuberculosis
      complex mycobacteria and the highly repeated DNA sequence, the polymorphic GC
      rich repeat sequence (PGRS), were systematically used to identify restriction
      fragment length polymorphisms (RFLPs) within 210 isolates of Mycobacterium bovis.
      The isolates were primarily of bovine origin, but isolates from badgers, feral
      deer, sheep, humans, and a pig were included. The RFLP probes IS6110, DR, and
      PGRS individually identified 17, 18, and 18 different RFLP types, respectively,
      but in combination these probes identified a total of 39 different M. bovis RFLP
      types. The recommendations (J. D. A. van Embden, M. D. Cave, J. T. Crawford, J.
      W. Dale, K. D. Eisenach, B. Gicquel, P. W. M. Hermans, C. Martin, R. McAdam, T.
      M. Shinnick, and P. M. Small, J. Clin. Microbiol. 31:406-409, 1993) for a
      standardized RFLP analysis for M. tuberculosis were adapted to facilitate gel
      documentation, image analysis, and construction of a database of RFLP types. In
      the present study the same M. bovis RFLP types were evident in the various animal
      species included, indicating that the strains were not host restricted.
      Application of these techniques to defined field studies should help elucidate
      more accurately aspects of the epidemiology of bovine tuberculosis in different
      countries.

PMID- 8880503
TI  - Monoclonal infection involving Mycobacterium avium presenting with three distinct
      colony morphotypes.
AB  - Recent reports indicate that polyclonal infections may play an important role in
      multiple drug resistance in Mycobacterium avium infections. We report here on the
      isolation of a single M. avium strain that appeared to have smooth colony
      morphology upon initial isolation on a Lowenstein-Jensen slant. Primary
      subculture onto Middlebrook 7H10, however, revealed three distinct morphotypes
      representing smooth opaque (SmO), smooth transparent (SmT), and rough (Rg) colony
      morphologies. All three morphotypes were identified as M. avium by standard
      biochemical procedures, Genprobe analysis, and mycolic acid patterns. Subsequent
      restriction fragment length polymorphism analysis, using SalI- and PvuII-digested
      genomic DNA, revealed identical patterns for hybridization with the IS1245 probe.
      Thin-layer chromatographic analysis of lipids from the three morphotypes revealed
      that only the SmT morphotype possessed what appeared to be lipid components
      similar to, but unlike, previously described serovar-specific glycopeptidolipid
      antigens. Further analysis of internally radiolabeled deacylated lipids from the
      SmT morphotype, by high-performance liquid chromatography and thin-layer
      chromatography, disclosed that some of these components can be internally
      radiolabeled with [14C] phenylalanine and [14C]mannose. These results suggest
      that these components are structurally similar to previously described
      glycopeptidolipid antigens. This is apparently the first report of a monoclonal
      infection involving a single strain of M. avium presenting with all three colony
      morphotypes, SmO, SmT, and Rg.

PMID- 8880504
TI  - Helicobacter canis isolated from a dog liver with multifocal necrotizing
      hepatitis.
AB  - On the basis of biochemical, phenotypic, and 16S rRNA analysis, a novel gram
      negative bacterium, isolated from normal and diarrheic dogs as well as humans
      with gastroenteritis, has been recently named Helicobacter canis. A 2-month-old
      female crossbred puppy was submitted to necropsy with a history of weakness and
      vomiting for several hours prior to death. The liver had multiple and slightly
      irregular yellowish foci up to 1.5 cm in diameter. Histologically, the liver
      parenchyma contained randomly distributed, occasionally coalescing hepatocellular
      necrosis, often accompanied by large numbers of mononuclear cells and
      neutrophils. Sections of liver stained by the Warthin-Starry silver impregnation
      technique revealed spiral- to curve-shaped bacteria predominantly located in bile
      canaliculi and occasionally in bile ducts. Aerobic culture of liver was negative,
      whereas small colonies were noted on Campylobacter selective media after 5 days
      of microaerobic incubation. The bacteria were gram negative and oxidase positive
      but catalase, urease, and indoxyl acetate negative; nitrate was not reduced to
      nitrite, and the organism did not hydrolyze hippurate. The bacteria were also
      resistant to 1.5% bile. Electron microscopy revealed spiral-shaped bacteria with
      bipolar sheathed flagella. By 16S rRNA analysis, the organism was determined to
      be H. canis. This is the first observation of H. canis in active hepatitis in a
      dog and correlates with recent findings of Helicobacter hepaticus- and
      Helicobacter bilis-related hepatic disease in mice. Further studies are clearly
      warranted to ascertain whether H. canis-associated hepatitis is more widespread
      in canines as well as a cause of previously classified idiopathic liver disease
      in humans.

PMID- 8880505
TI  - GlpQ: an antigen for serological discrimination between relapsing fever and Lyme
      borreliosis.
AB  - Tick-borne relapsing fever is caused by numerous Borrelia species maintained in
      nature by Ornithodoros tick-mammal cycles. Serological confirmation is based on
      either an immunofluorescence assay or an enzyme-linked immunosorbent assay using
      whole cells or sonicated Borrelia hermsii as the antigen. However, antigenic
      variability of this bacterium's outer surface proteins and antigens shared with
      the Lyme disease spirochete (B. burgdorferi), may cause both false-negative and
      false-positive results when testing sera of patients suspected to have either
      relapsing fever or Lyme disease. To develop a specific serological test for
      relapsing fever, we created a genomic DNA library of B. hermsii, screened
      transformed Escherichia coli cells for immunoreactivity with high-titered (> or =
      1:2,048) human anti-B. hermsii antiserum, and selected an immunoreactive clone
      (pSPR75) expressing a 39-kDa protein. DNA sequencing, subcloning, and serum
      adsorption experiments identified the immunoreactive protein as a homolog of
      GlpQ, a glycerophosphodiester phosphodiesterase identified previously in E. coli,
      Haemophilus influenzae, and Bacillus subtilis. Serum samples from humans and mice
      infected with B. hermsii or other species of relapsing fever spirochetes
      contained antibodies recognizing GlpQ, whereas serum samples from Lyme disease
      and syphilis patients were nonreactive. Serologic tests based on this antigen
      will identify people exposed previously to relapsing fever spirochetes and help
      clarify the distribution of relapsing fever and Lyme disease in situations in
      which the occurrence of their causative agents is uncertain.

PMID- 8880506
TI  - Identification of a variant subgroup A strain of respiratory syncytial virus.
AB  - During epidemiologic surveillance of children with respiratory syncytial virus
      (RSV) disease in Huntington, W.Va., we identified seven strains of a new variant
      subgroup A RSV (subgroup A-Var) by their reactions in an enzyme immunoassay with
      two anti-F monoclonal antibodies (MAbs) specific for two epitopes, F1 and F4,
      generated against the subgroup B RSV. The prototype strain of subgroup A and all
      other subgroup A field strains from that epidemiologic year failed to react with
      these two subgroup B MAbs. Additional enzyme immunoassays with 18 subgroup B anti
      F MAbs specific for 14 epitopes showed that subgroup A-Var strains also reacted
      with a MAb specific for the subgroup B F2 epitope. In a radioimmune precipitation
      assay, the molecular size of the subgroup A-Var F2 subunit of the fusion (F)
      protein clearly differed from those of both prototype strains of subgroup A and
      subgroup B RSV. The molecular size of the F2 subunit of subgroup A-Var (24 kDa)
      was intermediate between the size of the F2 subunit of subgroup A (25 kDa) and
      that of subgroup B (23 kDa). However, the molecular sizes of the F1 subunits of
      both subgroup A and subgroup A-Var were identical (54 kDa) and slightly larger
      than those of the F1 subunits of both subgroups B1 and B2 (53 kDa). These data
      suggest that subgroup A-Var may represent a distinct RSV A subgroup, analogous to
      subgroup B1 and B2 RSV, and it is the first-identified naturally occurring
      subgroup A RSV with an F protein different from that of the prototype A RSV.

PMID- 8880507
TI  - Vaginal microbiology of women with acute recurrent vulvovaginal candidiasis.
AB  - Alterations in the autochthonous vaginal microflora can predispose women to
      recurring attacks of Candida vaginitis. Quantitative aerobic and anaerobic
      cultures were obtained from 24 premenopausal women with acute recurrent
      vulvovaginal candidiasis and from 21 healthy asymptomatic premenopausal women.
      Lactobacillus species constituted the predominant flora in both groups, with a
      mean log10 CFU/ml of 8.7, a total isolation rate of 96%, and a mean of 1.6
      Lactobacillus species isolated per patient compared with a mean log10 CFU/ml of
      8.9, a total isolation rate of 90%, and a mean of 1.2 Lactobacillus species
      isolated per patient in the vaginitis and control groups, respectively. The
      results of this small study failed to provide evidence of an altered or abnormal
      vaginal bacterial flora in women with non-antibiotic-induced recurrent
      vulvovaginal candidiasis suffering from acute Candida vaginitis.

PMID- 8880508
TI  - Rapid identification of Toscana virus by nested PCR during an outbreak in the
      Siena area of Italy.
AB  - The sand fly-transmitted Toscana virus is recognized as an etiologic agent of an
      aseptic meningitis with a long convalescence. This infection has been reported
      overall in many tourists or in a seronegative population circulating in endemic
      Mediterranean areas (Italy, Portugal, Egypt, and Cyprus). We report a cluster of
      acute Toscana virus infections in the local population during the summer of 1995.
      Twenty-one clinical cases of meningitis were investigated for the presence of
      Toscana virus by nested PCR performed on the S segment of the virus RNA extracted
      from cerebrospinal fluid samples.

PMID- 8880509
TI  - Diagnostic antigenemia tests for penicilliosis marneffei.
AB  - Disseminated penicilliosis marneffei is an emerging opportunistic mycosis seen in
      severely immunocompromised human immunodeficiency virus (HIV)-infected patients
      and is caused by the dimorphic fungus Penicillium marneffei. Early diagnosis and
      treatment improve clinical outcome. Proper diagnosis is complicated by
      nonspecific signs and symptoms and by difficulties in histologic recognition and
      species identification of the pathogen. Since no established immunodiagnostic
      methods for penicilliosis marneffei are available, we attempted to develop
      separate immunodiffusion tests to detect P. marneffei antigens and antibodies in
      patient serum specimens and a latex agglutination test for antigenemia. Antigens
      consisted of 2-week-old fission arthroconidial filtrates produced in Pine's broth
      at 37 degrees C. Rabbit antisera were prepared against the 10 x -concentrated
      filtrate antigens. Studies were carried out with 17 serum specimens from HIV
      seropositive adult Thai patients with penicilliosis marneffei and 15 control
      serum specimens from Thai persons free of HIV and P. marneffei infection. The
      immunodiffusion tests detected P.marneffei antigenemia in 10 (58.8%) of 17
      patients, whereas the latex agglutination test detected antigenemia in 13 (76.5%)
      of the 17 patients. Antibody was demonstrated in only 2 of the 17 patient sera.
      All of the tests appeared to be highly specific, since none were positive with
      sera from 15 Thai control patients, six serum samples containing cryptococcal
      antigen, or six urine specimens positive for Histoplasma polysaccharide antigens.

PMID- 8880510
TI  - Application of 16S rRNA gene PCR to study bowel flora of preterm infants with and
      without necrotizing enterocolitis.
AB  - The purpose of the present study was to determine the extent to which bacteria
      not detected by culture contribute to the microbial flora of the bowel of preterm
      infants with and without neonatal necrotizing enterocolitis (NEC). Fecal samples
      from 32 preterm infants in special care baby units including samples from 10
      infants with NEC were examined by culture and PCR amplification of the 16S rRNA
      gene (rDNA). The 16S rDNA V3 region was amplified with eubacterial primers, and
      the amplification products derived from the fecal sample DNA were compared with
      the products from individual cultured isolates by PCR and denaturing gradient gel
      electrophoresis (PCR-DGGE), allowing the DNA from uncultured bacteria to be
      identified. For the 22 infants without NEC weekly samples were examined for a
      mean of 5.3 postnatal weeks. The total number of types detected by culture
      combined with PCR-DGGE was 10.1 per infant, of which PCR-DGGE contributed 10.4%
      of the types identified. Additional types detected by PCR-DGGE were found in 14
      (63.6%) of the 22 infants. The majority of the sequences associated with
      uncultured bacteria showed > 90% 16S rDNA sequence identity with sequences from
      culturable human enteric flora, and all were found in single infants with the
      exception of sequences indistinguishable by DGGE from seven infants. These
      sequences showed > 90% sequence identity with the 16S rDNA of Streptococcus
      salivarius and may have been derived from upper gastrointestinal or respiratory
      tract flora. In the present study uncultured bacteria detected by PCR-DGGE were
      no more frequent in fecal samples from infants with NEC than in samples from
      infants without NEC, although these findings do not exclude the possibility of
      unrecognized bacteria associated with the mucosa of the small intestine of
      infants with NEC.

PMID- 8880511
TI  - M proteins of group C streptococci isolated from patients with acute pharyngitis.
AB  - We studied 15 strains of group C (Streptococcus equi subsp. equisimilis)
      [corrected] isolated from the throats of college students with acute pharyngitis
      and 5 strains isolated from patients with noninfectious problems. Nineteen of the
      20 strains resisted phagocytic killing during incubation in normal human blood,
      suggesting that they might express M proteins. Genomic DNA from all 20 strains
      hybridized with a probe corresponding to the carboxyterminal one-third of the
      group A M-protein gene emm24, a region that is highly conserved among M proteins
      of group A and group G streptococci. The DNA sequences of the N-terminal
      (variable) regions of the M-protein-encoding genes from two disease-associated
      group C isolates and one control isolate were determined. The predicted amino
      acid sequences of the two pharyngitis strains were identical and were 88%
      homologous to the amino acid sequence of a group G M-protein gene. The predicted
      terminal amino acid sequence of the control strain does not correspond to any
      such sequences in the GenBank database. All three strains studied possess the
      conserved region domain common to class I group A M-protein types
      epidemiologically associated with rheumatic fever. These studies demonstrate the
      presence of M proteins in strains of S. equi subsp. equisimilis [corrected]
      isolated in cases of endemically occurring acute pharyngitis. Certain of these
      proteins are similar to those of group G streptococci, while others may represent
      new M types. The similarity in structure and function between M proteins of
      nonrheumatogenic serogroups and those of rheumatogenic group A streptococci
      suggests that factors other than or in addition to M protein per se are likely
      involved in the pathogenesis of rheumatic fever.

PMID- 8880513
TI  - Reliability of nucleic acid amplification for detection of Mycobacterium
      tuberculosis: an international collaborative quality control study among 30
      laboratories.
AB  - Nucleic acid amplification to detect Mycobacterium tuberculosis in clinical
      specimens is increasingly used as a laboratory tool for the diagnosis of
      tuberculosis. However, the specificity and sensitivity of these tests may be
      questioned, and no standardized reagents for quality control assessment are
      available. To estimate the performance of amplification tests for routine
      diagnosis, we initiated an interlaboratory study involving 30 laboratories in 18
      countries. We prepared blinded panels of 20 sputum samples containing no, 100, or
      1,000 mycobacterial cells. Each laboratory was asked to detect M. tuberculosis by
      their routine method of nucleic acid amplification. Only five laboratories
      correctly identified the presence or absence of mycobacterial DNA in all 20
      samples. Seven laboratories detected mycobacterial DNA in all positive samples,
      and 13 laboratories correctly reported the absence of DNA in the negative
      samples. Lack of specificity was more of a problem than lack of sensitivity.
      Reliability was not found to be associated with the use of any particular method.
      Reliable detection of M. tuberculosis in clinical samples by nucleic acid
      amplification techniques is possible, but many laboratories do not use adequate
      quality controls. This study underlines the need for good laboratory practice and
      reference reagents to monitor the performance of the whole assay, including
      pretreatment of clinical samples.

PMID- 8880512
TI  - Comparative study of three methods for genotyping hepatitis C virus strains in
      samples from Spanish patients.
AB  - Hepatitis C virus (HCV) genotypes may be investigated by a variety of laboratory
      methods that target different parts of the HCV genome and have various degrees of
      technical difficulty. Since the choice of a particular method is difficult, we
      compared the performance of (i) a type-specific PCR with type-specific primers
      from the core region, (ii) molecular hybridization of the PCR-amplified 5'
      noncoding region to type-specific probes, and (iii) identification of type
      specific antibodies against epitopes of nonstructural region 4 by enzyme-linked
      immunosorbent assay (ELISA). One hundred fifty-one patients with biopsy-proved
      chronic hepatitis and HCV RNA in serum were investigated. The HCV genotype was
      identified in 99%, 100%, and 85% of the cases by type-specific PCR, probe
      hybridization, and ELISA, respectively. The type-specific PCR disclosed infection
      with type 1a in 3%, type 1b in 74%, and type 3a in 4% of the cases and suggested
      infection with two or more HCV types, including 2a/2c and 2b, in the remaining
      18%. Apparently mixed infections were more prevalent in patients with past
      intravenous drug use (P < 0.001), but cloning and sequencing of PCR products did
      not confirm a mixed infection in any of the four cases investigated. Concordant
      results were obtained by the three procedures with virtually all of the samples
      in which the type-specific PCR revealed a single HCV genotype. Type-specific
      hybridization and ELISA usually recognized the genotype producing the strongest
      DNA band in samples in which type-specific PCR suggested a mixed infection. In
      conclusion, the three procedures evaluated in this study are reliable for
      investigation of HCV genotype. Type-specific PCR provides information about HCV
      subtypes, but a mixed infection detected with this method should be interpreted
      with caution.

PMID- 8880514
TI  - Study of Abbott Toxo IMx system for detection of immunoglobulin G and
      immunoglobulin M toxoplasma antibodies: value of confirmatory testing for
      diagnosis of acute toxoplasmosis.
AB  - We compared the Abbott Toxo immunoglobulin G (IgG) and IgM IMx assays with the
      Sabin-Feldman dye test and an IgM enzyme-linked immunosorbent assay (ELISA) in
      398 serum samples previously tested in our laboratory (retrospective group) and
      1,000 consecutive serum samples, tested as they were received in our laboratory
      in 1995 (prospective group). In the retrospective group, the IgG IMx had a
      sensitivity of 100%, specificity of 99.0%, positive predictive value of 99.0%,
      negative predictive value of 100%, and overall agreement of 99.5%. The
      percentages for the IgM IMx were 97.8, 99.0, 98.9, 98, and 98.4%, respectively.
      In the prospective group, the IgG IMx had a sensitivity of 97.8%, specificity of
      98.7%, positive predictive value of 97.8%, negative predictive value of 98.7%,
      and overall agreement of 98.4%. The percentages for the IgM IMx were 88.3, 95.9,
      74.7, 98.3, and 95%. A serological profile (IgA and IgE antibodies and the
      differential agglutination [AC/HS] test) was performed in an attempt to resolve
      discrepancies. Of 21 serum samples that were positive in the IgM IMx and negative
      in the IgM ELISA, 19 had serological profiles which were most compatible with an
      infection acquired in the distant past. Of 8 serum samples which were positive in
      the IgM ELISA and negative in the IgM IMx, 5 had serological profiles which were
      most compatible with an infection acquired in the distant past. Of the 55 serum
      samples that were positive in both IgM tests, 21 were from patients who had
      serological profiles which were most compatible with an infection acquired in the
      distal past. In conclusion, our data highlight the importance of confirmatory
      testing for the diagnosis of recently acquired infection with Toxoplasma gondii.
      When compared with the dye test and IgM ELISA, the Toxo IgG and IgM IMx assays,
      respectively, revealed high overall agreement in the retrospective and
      prospective study.

PMID- 8880515
TI  - Two different 16S rRNA genes in a mycobacterial strain.
AB  - Sequencing of the gene coding for 16S rRNA (16S rDNA) is a well-established
      method used to identify bacteria, particularly mycobacteria. Unique sequences
      allow identification of a particular genus and species. If more than one 16S rDNA
      is present on one mycobacterial genome, their sequences are assumed to be
      strictly or almost identical. We have isolated a slowly growing Mycobacterium
      strain, "X", identified by conventional biochemical tests as Mycobacterium
      terrae. Identification by amplification and direct sequencing of 16S rDNA yielded
      ambiguous results in two variable regions, suggesting the presence of different
      copies of the sequenced gene. Total DNA was digested by restriction enzymes and
      hybridized after Southern blotting to a probe representing about two-thirds of
      the 16S rDNA. Two copies of 16S rDNA were identified and cloned. By sequencing,
      the clones were of two different types, A and B, differing in 18 positions.
      Oligonucleotides specific to each copy of the 16S rDNA were used to distinguish
      the positions of the two genes observed in the Southern blot. We conclude that
      Mycobacterium strain "X" has two different copies of 16S rDNA. Variations in the
      sequence between two copies of 16S rDNA gene have been described in
      archaeobacteria, but not in mycobacteria. When placed in a phylogenetic tree
      together with other slowly growing mycobacteria gene A shows a common root with
      M. terrae, whereas gene B is placed separately.

PMID- 8880517
TI  - Assessment of routine use of an anaerobic bottle in a three-component, high
      volume blood culture system.
AB  - The relative value of routine anaerobic blood culture for recovery of organisms
      and identification of episodes of bloodstream infection was assessed in a three
      component, high-volume blood culture system which employs aerobic and anaerobic
      bottles of BacT/Alert (Organon-Teknika, Durham, N.C.) and aerobic cultures of
      Isolator (Wampole Laboratories, Cranbury, N.J.). The results of 5,595 blood
      culture sets from patients with suspected bloodstream infection were analyzed.
      Compared with either the aerobic BacT/Alert bottle or aerobic culture of
      Isolator, the BacT/Alert anaerobic bottle recovered significantly fewer isolates
      (242 versus 294, P < 0.05; 242 versus 298, P < 0.05) but did not detect
      significantly fewer episodes of bloodstream infection (141 versus 157, P > 0.05;
      141 versus 147, P > 0.05). The BacT/Alert anaerobic bottle recovered
      significantly more isolates of obligately anaerobic bacteria (16 versus 4, P <
      0.05; 16 versus 0, P < 0.05) and detected significantly more episodes of
      bloodstream infection caused by obligately anaerobic bacteria (10 versus 3, P <
      0.05; 10 versus 0, P < 0.05) than either the aerobic bottle of BacT/Alert or the
      aerobic culture of Isolator. The combination of the BacT/Alert anaerobic bottle
      and the aerobic culture of Isolator recovered as may isolates (374 versus 377)
      and detected as many episodes of bloodstream infection (194 versus 191) as the
      combination of the aerobic bottle of BacT/Alert and the aerobic culture of
      Isolator, and both of these combinations identified at least 8% more isolates and
      detected at least 3% more bloodstream infections than the combination of the
      BacT/Alert aerobic and anaerobic bottles. Further analysis of the data revealed
      that the utility of the BacT/Alert anaerobic bottle, especially when combined
      with the aerobic culture of Isolator, resulted from not only enhanced recovery of
      obligately anaerobic bacteria but also effective recovery of facultatively
      anaerobic bacteria. These results demonstrate the utility of the anaerobic
      BacT/Alert bottle for detecting bloodstream infection caused by either
      facultatively anaerobic bacteria or obligately anaerobic bacteria and support the
      routine inclusion of anaerobic blood culture in the three-component blood culture
      system used in our hospital.

PMID- 8880516
TI  - Temporal shifts in traits of Vibrio cholerae strains isolated from hospitalized
      patients in Calcutta: a 3-year (1993 to 1995) analysis.
AB  - This study presents results of a surveillance on cholera conducted with
      hospitalized patients admitted to the Infectious Diseases Hospital, Calcutta,
      India, from January 1993 to December 1995. The O139 serogroup of Vibrio cholerae
      dominated in 1993 but was replaced by O1 as the dominant serogroup in 1994 and
      1995. The isolation rate of V. cholerae non-O1 non-O139 did not exceed 4.9%
      throughout the study period, while the isolation rate of the O139 serogroup in
      1994 and 1995 was below 9%. No temporal clustering of any non-O1 non-O139
      serogroup was observed. With the exception of 1 strain, none of the 64 strains
      belonging to the non-O1 non-O139 serogroup hybridized with ctx, zot, and ace gene
      probes, while 97.3 and 97.7% of the O139 and O1 strains, respectively, hybridized
      with all the three probes. Multiplex PCR studies revealed that all the O1 strains
      belonged to the EIT or biotype. There was a progressive increase in the cytotoxic
      response on CHO and HeLa cells evoked by culture supernatants of strains of V.
      cholerae non-O1 non-O139 isolated during 1994 and 1995 compared with the response
      evoked by those isolated in 1993. Dramatic shifts in patterns of resistance to
      antibiotics between strains of V. cholerae belonging to different serogroups and
      within strains of a serogroup isolated during different time periods were
      observed. There was a discernible increase in the incidence of multidrug
      resistant strains of V. cholerae O1 isolated in 1994 and 1995 compared with that
      in 1993. On the basis of the results of this study, we predict the possibility of
      newer variants of V. cholerae emerging in the future.

PMID- 8880518
TI  - Detection of Neisseria gonorrhoeae from air-dried genital samples by single-tube
      nested PCR.
AB  - A single-tube nested PCR method was developed for the detection of Neisseria
      gonorrhoeae. The optimized assay had a detection limit of less than 0.3 cell.
      Five different storage conditions for gonococcal specimens were compared with
      respect to the PCR detection of bacteria. For air-dried gonococcal slides
      containing three bacteria, DNA was detected after 8 weeks at ambient temperature,
      and for slides containing 300 bacteria, DNA could be detected after 24 weeks at
      ambient temperature. Air-dried storage combined with analysis by the single-tube
      nested PCR and a commercially available PCR (Amplicor) was used to test 350
      cervical specimens from women in the West African island nation of Cape Verde.
      The in-house PCR detected 17 cases of N. gonorrhoeae infection, while the
      Amplicor system detected 14 cases of N. gonorrhoeae infection. No specimen was
      negative by the in-house PCR assay and positive by the Amplicor PCR. This
      sensitive nested PCR assay, combined with air-dried storage, allows for the
      detection of gonococci when specimen storage and transport times are extended and
      freezing conditions are not available.

PMID- 8880519
TI  - Hepatitis C virus detection by single-round PCR specific for the terminal 3'
      noncoding region.
AB  - A single-round PCR method with primers specific for the 3' noncoding region (NCR)
      of hepatitis C virus (HCV) has been developed. Using a double RNAzol-B
      extraction, a high-temperature reverse-transcription step with SuperScript II
      reverse transcriptase, and a 40-cycle two-temperature PCR with a TaqStart
      antibody hot-start procedure, we were able to detect a 92-nucleotide fragment of
      the recently discovered 98-nucleotide highly conserved sequence at the 3'
      terminus of the HCV genome. Direct sequencing of the PCR products confirmed the
      specificity of the PCR and demonstrated conservation in this region. Only one
      nucleotide change in 14 specimens was found. End point dilution titration of sera
      with known viral RNA titers showed the sensitivity of the single-round 3' NCR PCR
      to be comparable to those of the established nested 5' NCR assays (fewer than 25
      HCV genome equivalents). To evaluate specificity and sensitivity, a panel of 116
      serum samples characterized by nested 5'-end PCR, genotyping, and quantitative
      assays was tested. A high degree of concordance (96%) between the 3' NCR and 5'
      NCR PCR results was found. The sequence conservation at the 3' end of the HCV
      genome among common genotypes and the savings in time, labor, and reagents from a
      single-round PCR make this assay a useful addition to the detection systems
      available to identify and monitor HCV infection.

PMID- 8880520
TI  - Multicentric epidemiological study of Aspergillus fumigatus isolates by
      multilocus enzyme electrophoresis.
AB  - The genotypes of 63 isolates of Aspergillus fumigatus obtained from three
      hospitals in different geographical areas and of eight culture collection strains
      were determined by multilocus enzyme electrophoresis. Twelve of the 17 enzymatic
      loci studied were polymorphic, giving rise to 48 different electrophoretic types.
      The existence of fixed multilocus genotypes, significant heterozygote deficits
      and excesses at the different loci, and linkage disequilibria within
      subpopulations strongly suggests a clonal reproduction mode for A. fumigatus.
      Numerical analysis of the comparison and disposition of the different
      electrophoretic types demonstrates a significant genetic differentiation between
      the three sampling sites. However, no correlation could be found between
      geographical distances and genetic differentiation. On account of the multiple
      discriminatory markers, multilocus enzyme electrophoresis typing seems to be a
      very powerful tool for epidemiological and reproductive mode studies of A.
      fumigatus.

PMID- 8880521
TI  - Patterns of detection of Strongyloides stercoralis in stool specimens:
      implications for diagnosis and clinical trials.
AB  - Reported efficacies of drugs used to treat Strongyloides stercoralis infection
      vary widely. Because diagnostic methods are insensitive, therapeutic trials
      generally require multiple negative posttreatment stool specimens as evidence of
      drug efficacy. However, only a single positive stool specimen is usually required
      for study enrollment. To determine the reproducibility of detection of S.
      stercoralis larvae in the stool, 108 asymptomatic infected men submitted 25 g of
      fresh stool once a week for eight consecutive weeks for examination by the
      Baermann technique. During the 8-week study, 239 (27.7%) of 864 stool specimens
      were positive for S. stercoralis. Rates of detection of larvae in the stool
      specimens ranged from eight of eight specimens in 3 (2.8%) men to none of eight
      specimens in 36 (33.3%) men. Of 43 men for whom S. stercoralis was detected in at
      least two of the first four stool specimens, only 1 (2.3%) man tested negative on
      all of the next four specimens. In comparison, of 29 men who had detectable
      larvae in only one of the first four specimens, 22 (75.9%) tested negative on all
      of the next four samples. Thus, if these 29 men had been enrolled in a
      therapeutic trial between the first and second sets of four specimens, the
      efficacy of a drug with no activity against this parasite would have been
      estimated to be 76%. These data suggest that patterns of S. stercoralis detection
      vary widely among infected persons and that intermittent larval shedding can lead
      to inflated estimates of drug efficacy. Before a patient is entered in a clinical
      trial of drug efficacy, four consecutive stool specimens should be examined for
      S. stercoralis; only persons with two or more positive specimens should be
      enrolled.

PMID- 8880522
TI  - Survey of enterococcal susceptibility patterns in Belgium.
AB  - A national surveillance study was performed in order to identify the enterococci
      causing important infections, to determine their susceptibilities to first-choice
      agents for treatment, and to characterize the phenotypes and genotypes of the
      glycopeptide-resistant strains. A total of 472 isolates were collected between 15
      January and 15 April 1993. The ability of the API rapid ID 32 STREP gallery to
      identify enterococci was evaluated. The majority of the Belgian enterococci were
      identified as E. faecalis (89.4%). E. faecium and other enterococci were present
      in small percentages only (9.1 and 1.5%, respectively). The API rapid ID 32 STREP
      system identified 88.6% of the strains with an excellent or very good
      identification score. For the majority of the strains with uncertain
      identification scores, the results of a single test only were aberrant. Only 2.3%
      of the strains remained unidentified. High-level aminoglycoside resistance was
      widespread in E. faecalis (streptomycin, 50.8%; gentamicin, 8.7%), and the
      emergence of ciprofloxacin resistance was found to be associated with
      aminoglycoside resistance. E. faecium is generally more resistant to a wide range
      of antibiotics, but glycopeptide-resistant strains (1.5%) have not yet become
      widespread.

PMID- 8880523
TI  - Clinical isolates of Histoplasma capsulatum from Indianapolis, Indiana, have a
      recombining population structure.
AB  - A sample of 30 clinical isolates of Histoplasma capsulatum was analyzed to
      determine (i) whether genetic exchange is important in the life cycle of this
      fungus and (ii) whether distinct subpopulations which correlate with disease
      severity or host immune status exist. Eleven biallelic molecular markers were
      developed, with the frequency of the least common allele at each molecular locus
      ranging from 10 to 50%. Every isolate had a different, unique multilocus
      genotype. Data analysis indicated that frequent recombination occurs within the
      Indianapolis, Ind., population. There were no associations between isolates from
      the immunocompromised population or from those with different clinical
      manifestations of histoplasmosis.

PMID- 8880524
TI  - Gastric mucormycosis due to Rhizopus oryzae in a renal transplant recipient.
AB  - Gastric mucormycosis is a rare disease with a reported fatal outcome of 98%.
      Manifestations range from colonization of peptic ulcers to infiltrative disease
      with vascular invasion and dissemination. In our renal transplant patient a deep
      gastric ulceration infected with Rhizopus oryzae (class Zygomycetes), which is
      known to be an agent of mucormycosis, was diagnosed in the early posttransplant
      period after antirejection therapy. The infection was successfully managed with
      amphotericin B and omeprazole.

PMID- 8880525
TI  - Diagnosis of cytomegalovirus infection in pediatric Menetrier's disease by in
      situ hybridization.
AB  - A previously healthy 7-year-old boy presented with a protein-losing enteropathy
      secondary to a hypertrophic gastropathy. The diagnosis of cytomegalovirus (CMV)
      infection was established by detection of CMV inclusion bodies in gastric biopsy
      samples and by hybridization with a CMV probe. This report further strengthens
      the association between CMV and pediatric Menetrier's disease.

PMID- 8880526
TI  - Diff-Quik stain as a simplified alternative to Papanicolaou stain for
      determination of quality of endocervical specimens submitted for PCR detection of
      Chlamydia trachomatis.
AB  - The simple, rapid, two-step Diff-Quik stain procedure (Baxter Diagnostics) was
      compared with the Papanicolaou stain for microscopic determination of
      endocervical specimen quality. Results from 230 (98.7%) of 233 specimens stained
      by both methods indicated agreement between the two staining methods for
      detection of the endocervical cells or erythrocytes indicating specimen adequacy.
      By using the Amplicor Chlamydia trachomatis Test (Roche Diagnostic Systems) to
      detect C.trachomatis and the Diff-Quik stain to assess specimen adequacy, PCR
      positive results were obtained from 147 (9.1%) of 1,615 microscopically adequate
      specimens but from only 13 (2.2%) of the 583 inadequate specimens (P < 0.001).

PMID- 8880527
TI  - Direct activity of recombinant human lactoferrin against Helicobacter pylori.
AB  - We report the activity of recombinant human lactoferrin against Helicobacter
      pylori. Lactoferrin exerted a time- and dose-dependent action against 8 of the 13
      clinical isolates of H. pylori tested in vitro. These results highlight a
      potential therapeutic use for lactoferrin against H.pylori infection.

PMID- 8880528
TI  - Genotypic characterization of sequential Aspergillus fumigatus isolates from
      patients with cystic fibrosis.
AB  - Twenty-three sequential Aspergillus fumigatus sputum isolates, which had been
      collected over a period of 2 years, from two patients with cystic fibrosis were
      genotyped by random amplified polymorphic DNA PCR and restriction fragment length
      polymorphism analysis. In patient B, one genotype was predominantly present in
      the sputum samples, while in the other patient up to nine different genotypes
      were identified. This study suggests that different patterns of colonization with
      A.fumigatus exist in patients with cystic fibrosis.

PMID- 8880529
TI  - Rapid preparation of bacterial DNA for pulsed-field gel electrophoresis.
AB  - A disadvantage of genotyping bacterial strains by pulsed-field gel
      electrophoresis is that the procedure requires up to 6 days to complete. We
      modified a standard pulsed-field gel electrophoresis method (B.E. Murray, K.V.
      Singh, J.D. Health, B.R. Sharma, and G.M. Weinstock, J.Clin. Microbiol. 28:2059
      2063, 1990) so that it could be completed in less than 3 days. We successfully
      applied this method to the analysis of a variety of gram-positive and gram
      negative bacteria.

PMID- 8880530
TI  - Cokeromyces recurvatus isolated from pleural and peritoneal fluid: case report.
AB  - The zygomycetous mold Cokeromyces recurvatus was isolated from the pleural and
      peritoneal fluids of a 64-year-old man with a history of peptic ulcer disease and
      alcohol abuse. The patient presented to the hospital with severe abdominal pain
      and a ruptured duodenal ulcer. This is one of the few times that C.recurvatus has
      been isolated from a human source, and the organism may have contributed to the
      death of this patient.

PMID- 8880532
TI  - Acidification of methyl-alpha-D-glucopyranoside: a useful test to differentiate
      Enterococcus casseliflavus and Enterococcus gallinarum from Enterococcus faecium
      species group and from Enterococcus faecalis.
AB  - Enterococcus gallinarum and E. casseliflavus are difficult to differentiate from
      other enterococci, particularly E.faecium. The former two species were found to
      produce acid from methyl-alpha-D-glucopyranoside in phenol red broth, while
      E.faecalis strains and strains of the E.faecium species group, including
      E.faecium, E.durans, E. hirae, and E.mundtii, failed to produce acid from this
      substrate.

PMID- 8880531
TI  - Comparison of reverse transcription-PCR with tissue culture and other rapid
      diagnostic assays for detection of type A influenza virus.
AB  - We applied a reverse transcription (RT)-PCR assay for influenza A virus to
      combined nasal wash-throat swab specimens previously obtained from an outpatient
      pediatric population with acute respiratory illness during concurrent epidemics
      of influenza A virus and respiratory syncytial virus. The results of the RT-PCR
      assay were compared with those previously reported with virus cultivation and
      commercially available rapid diagnostic kits (E.A. Dominguez, L.H. Taber, and
      R.B. Couch, J. Clin. Microbiol. 31:2286-2290, 1993). With virus cultivation as
      the "gold standard", the RT-PCR assay had a sensitivity, specificity, and
      efficiency of 95, 98, and 97%, respectively, compared with 75, 100, and 93%,
      respectively, for the best diagnostic kit (Becton Dickinson Directigen). RT-PCR
      is an effective alternative to virus isolation for the detection of influenza A
      virus in clinical specimens.

PMID- 8880533
TI  - Surrogate disks for predicting cefotaxime and ceftriaxone susceptibilities of
      Streptococcus pneumoniae.
AB  - Cefotaxime- and ceftriaxone-resistant Streptococcus pneumoniae is now appearing
      in some medical centers, but 30-micrograms cefotaxime or 30-micrograms
      ceftriaxone disks are not reliable for detecting such strains. Studies were
      undertaken to select another cephalosporin disk that might be used as a screening
      test that could be used in conjunction with a 1-micrograms oxacillin disk. A 30
      micrograms cefuroxime disk is proposed: strains with zones > or = 28 mm in
      diameter are predictably susceptible to cefotaxime and ceftriaxone, and those
      with smaller zones should be further studied to confirm resistance to either
      drug. A 30-micrograms ceftizoxime disk may also be used as a screening test with
      zones > or = 26 mm indicating susceptibility, but cefuroxime disks are preferred.

PMID- 8880534
TI  - Ribosomal DNA typing of Haemophilus ducreyi strains: proposal for a novel typing
      scheme.
AB  - Local strains of Haemophilus ducreyi were characterized by ribosomal DNA
      fingerprinting in order to develop a typing scheme for this organism. Chromosomal
      DNAs from 30 strains were extracted, and restriction fragments were separated by
      agarose gel electrophoresis after cleavage with BglII, HindIII, HindII, and
      BstEII. Of the 30 local strains studied, nine BglII, eight HindIII, six HindII,
      and five BstEII ribotype patterns were observed. In order to develop a typing
      scheme, we correlated the ribotype patterns obtained with each of the four
      enzymes for each strain. By this scheme, 13 ribotypes designated b to n were
      defined among the local strains. This study demonstrates that there is a
      diversity of ribotypes among H. ducreyi strains in our area, which emphasizes
      that there are many strains responsible for chancroid. This novel typing scheme
      provides a useful tool for further epidemiological studies of chancroid.

PMID- 8880535
TI  - Comparison of the MUREX C. albicans, Albicans-Sure, and BactiCard Candida test
      kits with the germ tube test for presumptive identification of Candida albicans.
AB  - The MUREX C. albicans (MC)(Murex Diagnostics), Albicans-Sure (AS) (Clinical
      Standards Laboratories), and BactiCard Candida (BC) (Remel) test kits were
      compared with the germ tube (GT) test for the rapid, presumptive identification
      of Candida albicans. All three test kits detect the enzymes L-proline
      aminopeptidase and beta-galactosaminidase in yeast cells grown on culture media
      and are based on the principle that C. albicans produces both enzymes whereas
      other yeasts produce only one or neither of the enzymes. The organisms evaluated
      were fresh clinical isolates identified by methods routinely used in our
      laboratory (API 20C system and conventional methods) and included 303 C. albicans
      isolates, 153 Candida glabrata isolates, 70 Candida tropicalis isolates, 36
      Candida parapsilosis isolates, 13 isolates of other Candida spp., 5 Cryptococcus
      neoformans isolates, and 3 Saccharomyces cerevisiae isolates. The MC, AS, BC, and
      GT tests detected 299 (98.7%), 300 (99.0%), 301 (99.3%), and 287 (94.7%) C.
      albicans isolates, respectively. There was one false-positive result with both
      the MC and BC kits and two false-positive results with the GT test. The enzymatic
      methods evaluated in this study provide rapid and accurate alternatives to the GT
      test for the presumptive identification of C. albicans.

PMID- 8880536
TI  - Rapid identification of Salmonella serovars in feces by specific detection of
      virulence genes, invA and spvC, by an enrichment broth culture-multiplex PCR
      combination assay.
AB  - In order to make a rapid and definite diagnosis of Salmonella enteritis in
      children, an enrichment broth culture-multiplex PCR combination assay was devised
      to identify Salmonella serovars directly from fecal samples. Two pairs of
      oligonucleotide primers were prepared according to the sequences of the
      chromosomal invA and plasmid spvC genes. PCR with these two primers would produce
      either one amplicon (from the invA gene) or two amplicons (from the invA and spvC
      genes), depending on whether or not the Salmonella bacteria contained a virulence
      plasmid. The fecal sample was diluted 10- to 20-fold into gram-negative
      enrichment broth and incubated to eliminate inhibitory compounds and also to
      allow selective enrichment of the bacteria. One or two amplicons were obtained,
      the expected result if Salmonella bacteria were present. The detection limit of
      this PCR was about 200 bacteria per reaction mixture. The primers were specific,
      as no amplification products were obtained with 18 species and 22 isolates of non
      Salmonella bacteria tested which could be present in the feces or cause
      contamination. In contrast, when 23 commonly seen Salmonella serovars (38
      isolates) were tested, all were shown to carry the invA gene and seven
      concomitantly harbored the spvC gene of the virulence plasmid. This assay was
      applied to the diagnosis of Salmonella enteritis in 57 children who were
      suffering from mucoid and/or bloody diarrhea. Of the 57 children, 38 were PCR
      positive and 22 were culture positive. There were two culture-positive samples
      that were not detected by PCR. Thus, this PCR assay showed an efficiency of 95%
      (38 of 40), which is much higher than the 60% (24 of 40) by culture alone. Not
      only is this method more sensitive, rapid, and efficient but it will cause only
      an incremental increase in the cost of stool processing, since enrichment
      cultivation of fecal samples from diarrheal patients using gram-negative
      enrichment broth is a routine practice for identification in many diagnostic
      microbiology laboratories. This PCR method, therefore, has clinical application.

PMID- 8880537
TI  - Genotyping of hepatitis C virus isolates from Lebanese hemodialysis patients by
      reverse transcription-PCR and restriction fragment length polymorphism analysis
      of 5' noncoding region.
AB  - We have genotyped the 5' noncoding region of hepatitis C virus in Lebanese
      hemodialysis patients by reverse transcription-PCR and restriction fragment
      length polymorphism analysis. Of 50 patients, 15 had the expected 268-bp amplicon
      by reverse transcription-PCR. Specificity of the amplicons was confirmed by
      Southern hybridization. Restriction analysis of the amplicons showed the pattern
      for genotype 4 (common in the Middle East).

PMID- 8880538
TI  - Identification of Turicella otitidis isolated from a patient with otorrhea
      associated with surgery: differentiation from Corynebacterium afermentans and
      Corynebacterium auris.
AB  - Turicella otitidis is a newly described coryneform bacterium isolated from middle
      ear fluids. We report here on the diagnosis of a strain isolated from otorrhea.
      The API Coryne system (bioMerieux, Marcy I'Etoile, France) used alone failed to
      differentiate T. otitidis, Corynebacterium afermentans, and Corynebacterium auris
      (ANF group). Biochemical tests such as DNase, enzymatic reactions (API ZYM;
      bioMerieux), and carbon substrate assimilation tests (Biotype 100; bioMerieux)
      allow presumptive identification. However, only chemotaxonomy and molecular
      biology can achieve unequivocal differentiation among these three species.

PMID- 8880539
TI  - Assessment of enzyme immunoassay versus radioimmunoassay for detection of
      Legionella pneumophila serogroup 1 antigen in frozen urine specimens.
AB  - An enzyme immunoassay (EIA) was compared with a radioimmunoassay (RIA) for
      detection of Legionella pneumophila serogroup 1 antigen in 37 frozen urine
      samples. Among 18 samples positive by the RIA at the time of collection, 50% (9
      of 18) of stored specimens retained positivity when retested by the RIA whereas
      78% (14 of 18) of stored specimens retained positivity when retested by the EIA
      (P < 0.02). A false-negative result occurred after storage for 5 months or less
      if the original RIA result showed weak positivity.

PMID- 8880540
TI  - Modified thioglycolate medium: a simple and reliable means for detection of
      Trichomonas vaginalis.
AB  - Despite the declining rate of sexually transmitted diseases in developed
      countries, trichomoniasis is still one of the most common venereal infections.
      While diagnosis of this condition is commonly based on the microscopic wet-mount
      method, culture remains the most accurate single procedure for detecting the
      presence of Trichomonas vaginalis in clinical samples. In the present study, the
      efficacy of a modified formula of the commonly available thioglycolate medium was
      compared with that of the standard Diamond's medium for detection of T. vaginalis
      in samples from 176 women with vaginal symptoms. Thioglycolate medium
      supplemented with yeast extract, horse serum, and antimicrobial agents was as
      reliable as Diamond's medium for detection of T. vaginalis in vaginal fluid
      samples. Modified thioglycolate medium may be used as a readily available, low
      cost substitute for the standard medium for culturing T. vaginalis.

PMID- 8880541
TI  - Salivary antibodies to cytomegalovirus (CMV) glycoprotein B accurately predict
      CMV infections among preschool children.
AB  - Among preschool children, we found an association between cytomegalovirus (CMV)
      infection and salivary immunoglobulin G antibodies to CMV glycoprotein B. All of
      the 20 infected children had immunoglobulin G to CMV glycoprotein B in their
      saliva, whereas 38 of 38 uninfected children lacked these antibodies. Testing
      saliva provides a sensitive and specific alternative to obtaining serum.

PMID- 8880542
TI  - Prevalence of human herpesvirus 8 DNA sequences in several patient populations.
AB  - We have undertaken a large-scale study of various tissues from normal controls
      and patients with Kaposi's sarcoma (KS) or other malignancies, both with and
      without human immunodeficiency virus infection, to determine the prevalence of
      human herpesvirus 8 (HHV-8) DNA. A total of 566 specimens were analyzed by PCR
      for the presence of HHV-8 DNA. Of the samples tested, 251 were obtained from
      patients with KS and 315 were obtained from patients without KS. HHV-8 DNA was
      detected in 103 (41%) of the 251 samples from patients with KS. In particular,
      92% of KS tumor specimens were positive. None of the tissues from patients
      without KS showed evidence of HHV-8 DNA. Sequencing and phylogenetic analyses
      indicate a high degree of conservation (97.5 to 100%) among the HHV-8 strains
      tested.

PMID- 8880543
TI  - Immunohistochemical detection of prion protein in lymphoid tissues of sheep,
      cattle, and humans.

PMID- 8880544
TI  - Impact of chlorhexidine-silver sulfadiazine-impregnated central venous catheters
      on in vitro quantitation of catheter-associated bacteria.

PMID- 8880545
TI  - Suction apparatus and the suctioning procedure: reducing the infection risks.
AB  - Serious infection has been related to the use of suction apparatus and to the
      suctioning procedure. Prevention of infection focuses on aseptic technique,
      handwashing, decontamination and sterilization of apparatus where appropriate.
      This article considers the infection risks arising from use of suction apparatus,
      the suctioning procedure and sets out recommendations for infection prevention.

PMID- 8880546
TI  - Risk factors for nosocomial infections caused by gram-negative bacilli. The
      Hellenic Antibiotic Resistance Study Group.
AB  - Two hundred and ninety-nine Gram-negative hospital-acquired infections from 257
      patients, consecutively identified during one month (November 1992) in five
      hospitals in the greater Athens area, were divided into four groups on the basis
      of the bacterium isolated: Group 1 (Escherichia coli group) included infections
      owing to E. coli, Group 2 (Proteus group) consisted of infections owing to
      Proteus spp. and Providencia spp., Group 3 (Kiebsiella/Enterobacter group)
      involved infections owing to Kiebsiella spp., Enterobacter spp., Citrobacter spp.
      and Serratia spp. Infections owing to Pseudomonas spp. and other non-fermenters
      were allocated into Group 4 (non-fermenters group). The four groups were studied
      in relation to risk factors including the duration of hospitalization, type of
      ward, underlying disease, history of operation, medical procedures/devices and
      antimicrobial therapy. A stepwise multiple logistic regression technique (SPSS
      Inc) was used to analyse the data, and the three groups (the Proteus group, the
      Klebsiella/Enterobacter group and the non-fermenters group) were analysed
      separately against the E. coli group. Infections with the Kiebsiella/Enterobacter
      group were associated with: (a) length of hospital stay before the infection, (b)
      treatment with newer antibiotics, and (c) hospitalization in an intensivecare
      unit (ICU). Infections with non-fermenters were associated with: (a) length of
      hospital stay before infection, (b) a urinary catheter, (c) type of disease
      (chronic infection being negatively associated), (d) treatment with newer
      antibiotics and (e) hospitalization in an ICU. Proteus group infections were
      associated with (a) length of hospital stay before infection, (b) treatment with
      newer antibiotics and (c) operation during present hospitalization (negative
      association). Interestingly, no specific hospitals were identified as risk
      factors. Identification of patients at risk for acquiring an infection owing to a
      nosocomial pathogen is vital in the development of a preventive strategy for
      hospital-acquired infections.

PMID- 8880547
TI  - Financial burden of hospital-acquired Clostridium difficile infection.
AB  - Clostridium difficile infection has become endemic in many hospitals and yet few
      data on the associated costs of such cases are available. We prospectively
      followed 50 consecutive cases of C. difficile infection and 92 control patients,
      who were admitted to the same geriatric wards within 72 h of the cases. Cases and
      controls had similar age, sex and major diagnosis distributions. Cases stayed
      significantly longer (mean 21.3 days, median 20.5 days; P < 0.001) in hospital
      than controls, including an average 14 days in a side room. Diarrhoea developed
      in cases on average 10.8 days after admission, which, when compared with a mean
      duration of stay for controls of 25.2 days, implies that C. difficile infection
      caused an increased duration of stay, as opposed to infection occurring because
      of longer residence. There was a significantly higher death rate in cases
      compared with controls (P < 0.01). Antibiotic treatment of C. difficile infection
      cost an average of Pounds 47 per case. The average number of laboratory
      investigations per day was similar for cases and controls, but the increased
      length of stay meant an extra cost for tests of approximately Pounds 210 per
      case. Assuming hotel costs of Pounds 150 (Pounds 200) per day stay (in a side
      room), 94% of the additional costs associated with C. difficile infection were
      due to increased duration of stay (Pounds 3850). The total identifiable increased
      cost of C. difficile infection was, therefore, in excess of Pounds 4000 per case.
      Such high costs can be used to justify expenditure on personnel and/or other
      control measures to reduce the incidence of this hospital-acquired infection.

PMID- 8880548
TI  - A comparison of methods to determine whether clinical isolates of Staphylococcus
      epidermidis from the same patient are related.
AB  - Staphylococcus epidermidis is a major cause of hospital-acquired infections but
      also part of the normal skin flora. A common clinical question is whether
      repeated isolation of S. epidermidis from one patient represents the same strain;
      because if different strains are isolated, they are often thought to be
      contaminants. In this study, different typing methods were compared to answer
      this question. Twenty isolates of S. epidermidis from five different patients
      were investigated. The isolates from each patient had identical or very similar
      antibiograms, and were recovered on different occasions. Typing was performed by
      antibiogram, biotype, slime production, plasmid profile, and pulsed-field gel
      electrophoresis (PFGE) banding pattern of SmaI digests of chromosomal DNA. In
      addition, the level of resistance to methicillin was determined by growth curves
      in broth containing methicillin for a series of different inocula for each
      isolate. The results showed that the isolates from each patient belonged to the
      same clone, but examples of instabilities in their antibiograms, plasmid
      profiles, as well as their PFGE banding patterns were seen. A change in the level
      of methicilli, resistance was observed in one strain; otherwise this
      characteristic was found to be strain-specific and stable in vivo. It was
      concluded that in combination with biotyping and antibiotic resistance testing
      the level of resistance to methicillin could be used as an aid to distinguish
      between two or more clinical isolates of S. epidermidis from the same patient.

PMID- 8880549
TI  - Antimicrobial activity of superoxidized water.
AB  - We tested the antimicrobial activity of superoxidized water against methicillin
      sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus,
      Staphylococcus epidermidis, Serratia marcescens, Escherichia coli, Pseudomonas
      aeruginosa and Burkholderia cepacia. The number of bacteria was reduced below
      detection limit following incubation in superoxidized water for 10 s. The
      bactericidal activity of superoxidized water was similar to that of 80% ethanol,
      but superior to that of 0.1% chlorhexidine and 0.02% povidone iodine. We conclude
      that superoxidized water is a low cost but powerful disinfectant.

PMID- 8880550
TI  - Bacterial contamination of commercially available ethacridine lactate (acrinol)
      products.
AB  - Bacterial contamination of commercially available ethacridine lactate (acrinol)
      solutions and cotton gauze soaked in ethacridine lactate solution was
      investigated. Of 56 samples from ethacridine lactate solutions (eight products,
      seven manufacturers), seven samples (12.5%) of two products (two manufacturers)
      were contaminated with 10(1)-10(4) colony forming units (cfu)/mL of Burkholderia
      pickettii. Of 67 samples obtained from gauze soaked in ethacridine lactate
      solution (seven products, seven manufacturers), 41 (61.2%) of six products (six
      manufacturers) were contaminated with 10(2)-10(6) cfu/mL of bacteria. The major
      bacteria detected were Burkholderia cepacia and Burkholderia pickettii. This
      relatively high incidence of bacterial contamination in commercially available
      cotton gauze soaked in ethacridine lactate solution may be due to the presence of
      gauze in ethacridine lactate solution.

PMID- 8880551
TI  - An outbreak of pseudobacteraemia caused by Burkholderia pickettii: the critical
      role of an epidemiological link.
AB  - A protracted outbreak of pseudobacteraemia caused by Burkholderia pickettii is
      reported. Initial investigation did not reveal the source of the outbreak.
      Subsequently, careful examination of patient records provided an insight to the
      probable source, which was further confirmed by a case control study. It was
      found that 48% of cases had either hepatobiliary diseases or haematological
      malignancies, whereas only 15% of the controls had similar problems. Furthermore,
      a coagulation study was performed on all of the cases on the day the blood
      culture was taken, but was performed on only 17% of the controls. With the
      establishment of this epidemiological link, a breakdown in aseptic blood culture
      technique was suspected. B. pickettii was isolated from citrated bottles used in
      the wards and from the citrate solution stocked in the haematology laboratory.
      The clonality of these strains was established by the pulsed-field gel
      electrophoresis (PFGE) and the arbitrary primed-polymerase chain reaction (AP
      PCR). The phlebotomists were notified of the findings of the outbreak
      investigation, and the importance of strict adherence to the aseptic blood
      culture technique was re-emphasized.

PMID- 8880552
TI  - Patient to patient hepatitis B transmission during heart biopsy procedures. A
      report of the European Working Party on Viral Hepatitis in Heart Transplant
      Recipients.

PMID- 8880553
TI  - Creative infection control--raising awareness of infection control policies.

PMID- 8880554
TI  - Stenotrophomonas maltophilia bacteraemia in cancer patients: report on 31 cases.

PMID- 8880555
TI  - Bacterial contamination of autologous bone marrow during processing.

PMID- 8880556
TI  - Review: calcium antagonists and diuretics; a useful combination in the management
      of hypertension?
AB  - The use of the combination of a calcium antagonist with a thiazide diuretic for
      the treatment of hypertension has been the subject of much debate over a number
      of years. Early studies, with few subjects, demonstrated little benefit, but more
      recent research using larger numbers of subjects has shown quite clear additional
      antihypertensive effects of this combination. Combination therapy has an
      important role in the treatment of patients who do not respond to monotherapy,
      and the combination of a calcium antagonist and thiazide diuretic may be useful
      in the successful treatment of these patients.

PMID- 8880557
TI  - Double-blind, parallel, comparative multicentre study of a new combination of
      diltiazem and hydrochlorothiazide with individual components in patients with
      mild or moderate hypertension.
AB  - OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a new
      combination preparation of diltiazem (150 mg) and hydrochlorothiazide (12.5 mg)
      with the individual constituents in patients with mild/moderate hypertension.
      DESIGN: Multi-centre, double-blind, randomised parallel group study. PATIENTS:
      Seventy-one patients with essential hypertension were recruited to the study.
      TREATMENT: Following completion of the placebo run-in period 63 patients
      fulfilled the prerandomisation criteria and entered the 10 week treatment period.
      Patients were randomised to receive either the combination preparation (D 150
      mg/H 12.5 mg), diltiazem (150 mg) or hydrochlorthiazide (12.5 mg). The dosage was
      increased in three patients who had not attained target blood pressure (BP)
      control after 6 weeks. OUTCOME MEASURES: Response to treatment assessed by change
      from baseline in clinic and 24 h ambulatory BP. RESULTS: The proportion of
      patients achieving target BP (a reduction in resting supine diastolic blood
      pressure (DBP) to below 90 mm Hg or a reduction of 10 mm Hg from baseline) was
      80% in the combination group, 55% in the diltiazem group, and 38% in the
      hydrochlorothiazide group. The respective figures for reduction in supine DBP
      from baseline were 13.5 mm Hg, 11.2 mm Hg and 5.9 mm Hg. A similar treatment
      order appeared throughout each of the efficacy variables. BP control throughout
      the 24 h dosing interval was demonstrated by ambulatory BP monitoring. Each
      treatment was well tolerated. CONCLUSION: This study provides clear evidence of
      the efficacy of combination therapy with diltiazem and hydrochlorothiazide in the
      management of patients with hypertension.

PMID- 8880558
TI  - Measurement of blood pressure may be affected by an interaction between subject
      and observer based on gender.
AB  - Retrospective studies have suggested that blood pressure (BP) may be affected by
      a covert gender interaction between patient and observer, which is most marked
      for female patients and male observers. Such an effect could be one of the
      determinants of the "white coat' response. We have assessed this interaction in a
      prospective study in 56 hospital outpatients (31 males, 25 females) in whom
      supine and erect BP and heart rate were measured by two male and two female
      subjects, and by an automatic sphygmomanometer when no persons were present.
      Supine systolic BP (SBP) was related to age, and fell progressively over three
      measurements. Absolute BP was less in females but the fall on repeated
      measurement was significantly greater than in males. When absolute BP was
      analysed by patient and observer sex, no significant interaction was present. BP
      measured by automatic sphygmomanometry was less than the value obtained
      clinically. Absolute BP showed no significant interaction with observer and
      patient sex, but the difference between machine and age-adjusted clinical
      measurements for SBP was significantly greater in female patients when BP was
      measured by male observers. However, this effect dissipated on repeated
      measurement. These data suggest that a transient gender interaction can
      contribute to the white-coat effect, especially in female patients when BP is
      measured by a male observer.

PMID- 8880559
TI  - Spouse concordance of obesity, blood pressures and serum risk factors for
      atherosclerosis.
AB  - Familial aggregation of atherosclerotic risk factors is well known, however inter
      spouse relation of the risk factors has remained controversial. As spouses are
      not blood-related, any risk factor relation probably does not reflect genetic
      factors, but the environmental factors to which the couple is exposed. Moreover,
      the effect of assortative marriage should be considered. The present study
      enrolled 97 married couples who attended a general health screening in 1993 in a
      mountain village of Japan. The screening was conducted between April and November
      at a single outpatient clinic in the village. Data on weight, height, blood
      pressure (BP), serum risk factors for atherosclerosis and marriage year were
      obtained as part of the screening programme. They were divided into three groups
      according to marital duration. The simple correlation coefficients for
      systolic/diastolic BP between the spouses were 0.22/0.19. The coefficients
      declined to 0.05/0.08 after controlling. The correlation coefficients for serum
      lipoproteins were low and between -0.06 and 0.11 after controlling. The
      correlation coefficients for blood sugar were -0.05 and -0.13 after controlling.
      In subgroup analyses stratified by marital duration, the correlation coefficients
      for BP, body mass index (BMI) and blood sugar were increased in both the short
      and long marital duration groups. The correlation coefficients for high-density
      lipoprotein (HDL) cholesterol and triglycerides increased with longer marital
      duration. Although a larger population study will be needed to confirm these
      findings, these results suggest the presence of interspouse correlation and
      reflect the influence of assortative marriage and environmental factors on spouse
      concordance.

PMID- 8880560
TI  - The mortality risk associated with hypertension: preliminary results of a
      prospective study in rural Nigeria.
AB  - The contribution of hypertension to adult mortality in Africa has not been well
      studied. Although cross-sectional surveys have provided data on the prevalence of
      this condition, the relative risk of death associated with hypertension has not
      been defined. In the face of high levels of competing mortality from infectious
      disease among the general population, and the virtual absence of atherosclerotic
      precursors, estimates of risk derived from industrialised countries may not be
      generalisable to this setting. We conducted a 2-year prospective study among 1344
      mean and women in a rural community in south-western Nigeria. The prevalence of
      hypertension (140/90 mm Hg) at baseline was 9.3%. In the observational phase,
      3.0% of the survey participants died each year. Among the 74 decedents,
      hypertension was nearly twice as common as among those who survived (14.9% vs
      8.4%). In multivariate analysis the risk of death increased over 60% for a 20 mm
      Hg increase in diastolic blood pressure. The population attributable risk, or the
      reduction in mortality that would have been observed if hypertension were not
      present in this community, was estimated as 7%. These findings document an
      identifiable impact of hypertension on all-cause mortality in rural Africa and
      demonstrate that programs to evaluate potential treatment options are needed.

PMID- 8880561
TI  - Hypertension epidemiology in India: meta-analysis of 50 year prevalence rates and
      blood pressure trends.
AB  - Recent studies among Indians have shown a high prevalence of hypertension. To
      determine changing trends in hypertension prevalence, in mean blood pressure (BP)
      levels and to study urban and rural differences we performed meta-analysis of all
      available Indian studies. The first such study was reported by Chopra in 1942.
      Since then many studies (n = 33) in urban and rural areas of India have been
      performed. In urban populations earlier studies of Dotto (1949), Dubey (1954) and
      Sathe (1959) showed prevalence of hypertension of 1.24 +/- 0.2, 4.24 +/- 0.4 and
      3.03 +/- 0.3% in populations of Calcutta, Kanpur and Bombay respectively. Studies
      since 1959 used World Health Organisation (WHO) guidelines and have shown
      increasing trend in hypertension prevalence. Recent studies from Ludhiana (1985)
      and Jaipur (1995) show that prevalence is 14.08 +/- 1.1 and 10.99 +/- 0.7%
      respectively. Trend analysis in studies among urban areas (n = 10) shows a
      significant increase in hypertension prevalence (Mantel-Haenzel chi 2 = 5.99, P =
      0.014). Studies in rural areas (n = 14) also show a significant increase in
      hypertension prevalence (Mantel-Haenzel chi 2 = 5.93, P = 0.014) although the
      rise is not as sharp as in urban populations (r value, urban = 0.70, rural =
      0.67). Changes in mean BP levels were analysed by using mean systolic (S) and
      diastolic (D) BP in urban men aged 40-49 years from 1959-1995. For SBP there was
      a significant increase (r = 0.95, P < 0.001) and not with DBP (r = 0.43, P >
      0.2). It is concluded that in India hypertension is emerging as a major health
      problem more so in urban than in rural subjects. The increasing prevalence is
      related to a rising mean SBP.

PMID- 8880562
TI  - Abnormalities of erythrocyte sodium transport in reflux nephropathy.
AB  - Hypertension is a complication of reflux nephropathy commonly occurring during
      adolescence and young adult life. We studied cellular sodium transport in an
      adolescent cohort with this condition as abnormal sodium transport is a feature
      of human hypertension. Thirty males and 52 females with reflux nephropathy,
      (median age 20.3 years) had erythrocyte ouabain sensitive sodium-potassium ATPase
      (Na/K ATPase) pump site number (Bmax) and red cell sodium concentration (RBC Na+)
      measured in 1988. Six years later, 55 of those had red cell sodium-lithium
      counter transport (LCT) measured. On both occasions, their renal function and
      blood pressure (BP) were determined. Bmax in the study group (median 10.3 nmol/l)
      was significantly less than that of controls (median 11.45 nmol/l). Nine patients
      who were diagnosed as having hypertension during the 6 year study period appeared
      to have a lower Bmax compared with that of normotensives in the group. RBC Na+
      and LCT of the study group were not significantly different from that of
      controls. The Na/K ATPase activity is diminished, and sodium-lithium counter
      transport is unchanged in reflux nephropathy. Further study is needed to
      ascertain the link between these observations and the onset of high BP.

PMID- 8880563
TI  - Role of endogenous ouabain-like substance during graded exercise in hypertensive
      individuals.
AB  - Changes in plasma endogenous ouabain-like substance (EOLS) and plasma
      noradrenaline, along with changes in blood pressure (BP), heart rate, and blood
      lactate concentration, were investigated in hypertensive individuals during
      strenuous exercise testing. Thirteen (4 men and 9 women) middle-aged (34-63
      years, mean 50 +/- 2 years) patients with mild essential hypertension underwent
      graded multistage submaximal exercise testing on a cycle ergometer. The workload
      in each exercise test was increased depending on the individual's physical
      fitness until they reached 75-80% of the predicted age-adjusted maximal heart
      rate prescribed by the American College of Sports Medicine. Systolic (S) BP rose
      by 67 +/- 9 mm Hg (P < 0.001), mean (M) BP by 28 +/- 3 mm Hg (P < 0.001),
      diastolic (D) BP by 9 +/- 2 mm Hg (P < 0.005) and heart rate by 79 +/- 6
      beats/min (P < 0.001) after submaximal graded exercise. The blood lactate
      concentration and plasma noradrenaline increased significantly (+3.40 +/- 0.34
      mmol/l and +895 +/- 94 pg/ml respectively, P < 0.001). Although the change in
      EOLS was not significant, it showed a strong positive correlation with the change
      in plasma noradrenaline (R = 0.760, P < 0.001). These results suggest that EOLS
      may participate in modifying sympathetic vasoconstriction during submaximal
      graded exercise.

PMID- 8880564
TI  - Changes in blood pressure and serum cholesterol following exercise training in
      Nigerian hypertensive subjects.
AB  - The effect of exercise training on blood pressure (BP) and serum cholesterol
      level was studied in hypertensive Nigerians. Fifty-eight subjects aged 30-65
      years completed the study. They exercised on a cycle ergometer at 70% maximum O2
      consumption. The frequency of exercise increased from 1 x 30 min/week for 16
      weeks to 3 x 30 min/week for 16 weeks. Overall, there was a significant decrease
      in systolic (S) BP from 161 mm Hg at the onset, to 148 mm Hg at the end of
      exercise training (P < 0.01). Also there was a significant decrease in diastolic
      (D) BP from 100 mm Hg to 95 mm Hg (P < 0.05). The younger hypertensives (30-50
      years) had a better response than the older hypertensives (51-65 years). There
      was a slight decrease in total cholesterol and low density lipoprotein levels,
      but high density lipoprotein level increased from an onset value of 0.94 mmol/l
      to 1.38 mmol/l at the end of exercise training (P < 0.05). Thus exercise training
      decreased BP and increased high density lipoprotein in hypertensive Nigerians.

PMID- 8880565
TI  - Hemodynamic and 24-h blood pressure profile of amlodipine monotherapy.
AB  - OBJECTIVES: To test the therapeutic efficacy, hemodynamic profile, changes in
      arterial compliance, left ventricular mass and side effects of amlodipine
      monotherapy in hypertensive Egyptians. BACKGROUND: Amlodipine is a
      dihydropyridine calcium antagonist with prolonged duration of action. Its
      hemodynamic and hypotensive effects were not reported in hypertensive Egyptians.
      Hypertension is a major health problem in Egypt. Racial differences in
      hypotensive efficacy of some drugs have been described. METHODS: Thirty-two
      hypertensive patients in stages I and II WHO were recruited from a hypertension
      clinic. Following 2-4 weeks placebo period 23 patients satisfied inclusion
      criteria of DBP 95-115 mm Hg. Active amlodipine therapy 5-10 mg was given once
      daily. Office BP was measured at monthly intervals for 3 months. Ambulatory 24-h
      blood pressure (ABP) and echo-Doppler studies were performed at the end of
      placebo and after amlodipine therapy. RESULTS: Twenty patients completed the 3
      months active treatment period, their age ranged from 30-63 years; 13 were males,
      body mass index (BMI) was 31 +/- 14 kg/m2 (mean +/- s.d.). Office systolic (S) BP
      decreased from 152 +/- 14 to 133 +/- 8 mm Hg, diastolic (D) BP from 104 +/- 6 to
      89 +/- 8 mm Hg, BP was normalised ( < 140/90 mm Hg) in 13 patients. Heart rate
      did not change. ABP 24 h, day-time, night time and early morning readings
      decreased significantly. Amlodipine attenuated SBP rises ( > 140 mm Hg) from 62%
      to 28% (P < 0.001) and DBP ( > 90 mm Hg) from 73% to 46% (P < 0.001). Cardiac
      index and left ventricle (LV) functional shortening did not change while systemic
      vascular resistance decreased from 35 to 29.8 units (P < 0.001). LV mass index
      decreased from 101 to 96 gm/m2 (NS) and arterial compliance increased from 0.97
      to 0.99 ml/mm Hg (NS). Oedema of lower limbs developed in six patients and was
      the only side effect. CONCLUSION: Amlodipine effectively lowered BP when given as
      monotherapy to hypertensive Egyptians. It did not influence heart rate, cardiac
      index or myocardial contractility. Change in LV mass and arterial compliance were
      not significant.

PMID- 8880566
TI  - Case report: fatal verapamil overdosage despite intensive therapy and use of high
      dose intravenous calcium.
AB  - Although the initial treatment of choice in calcium antagonist poisoning is
      calcium, there has been controversy over the optimal regime of its
      administration. The administration of prolonged or regular, high doses of calcium
      has been suggested. We report a fatal case of verapamil overdosage which did not
      respond to intensive therapy and very high doses of intravenous calcium, despite
      achieving extremely high serum calcium levels.

PMID- 8880567
TI  - Plasma erythropoietin concentration in patients with pheochromocytoma.

PMID- 8880568
TI  - Design and baseline characteristics of a hypertension intervention program in a
      South African village: patient awareness and understanding of their disease
      process are important.

PMID- 8880569
TI  - BRCA1 mutations in a selected series of breast/ovarian cancer patients.
AB  - Germline mutations in the BRCA1 gene have been associated with familial breast/
      ovarian cancer in large families showing high penetrance of the disease. Little
      is known, however, about the contribution of BRCA1 mutations to breast/ovarian
      cancer in small families with few affected members or in isolated early onset
      cases. Therefore we examined the BRCA1 gene in 63 breast/ovarian cancer patients
      who either came from small families with as few as one affected first degree
      relative, or in patients who had no family history but had developed breast
      cancer under 40 years of age. Using the protein truncation test, we were able to
      identify three unique BRCA1 germline mutations (4.8%). Two of the probands had
      only one affected first degree and several second degree relatives and the third
      had three affected first degree relatives including two sisters who, when tested,
      were also found to carry the mutation. There was no family history of ovarian
      cancer in any of the three families.

PMID- 8880570
TI  - Mutation screening of MSH2 and MLH1 mRNA in hereditary non-polyposis colon cancer
      syndrome.
AB  - Germline mutations in four human mismatch repair genes (MSH2, MLH1, PMS1, and
      PMS2) have been reported to cause hereditary non-polyposis colon cancer syndrome
      (HNPCC). The identification of germline mutations in HNPCC kindreds allows
      precise diagnosis and accurate predictive testing. To investigate further the
      genetic epidemiology of HNPCC and the nature and frequency of germline mutations
      in this disorder, we studied 17 English HNPCC kindreds for germline mutations in
      MSH2 and MLH1. A previous genetic linkage study had suggested that most English
      HNPCC families will have mutations in one of these genes. Mutation analysis was
      performed in a three step process. (1) mRNA extracted from lymphoblastoid cell
      lines was analysed for gross rearrangements, (2) the in vitro transcription
      translation (IVTT) assay was then performed to detect protein truncating
      mutations, and (3) partial cDNA sequencing of MSH2 or MLH1 was undertaken in
      families (n = 6) linked to MSH2 or MLH1 but without a detectable mutation. Seven
      different germline mutations were identified in eight of 17 (47%) kindreds (five
      in MSH2 and three in MLH1). In three cases there was a deletion of a single exon
      in MSH2 mRNA, three mutations resulted in a truncated protein product, and two
      missense mutations were identified by direct sequencing. Six mutations were
      novel. No precise correlation between genotype and phenotype was observed,
      although a MSH2 missense (Thr905Arg) mutation was associated with a
      susceptibility to multiple colorectal polyps. Age related risks for colorectal
      and uterine cancer were similar for MSH2 and MLH1 mutations.

PMID- 8880571
TI  - Attitudes towards cancer predictive testing and transmission of information to
      the family.
AB  - Before the organisation of breast cancer predictive testing in France,
      consultands' attitudes towards this kind of testing and towards passing on
      information about the family cancer risk to their relatives were investigated.
      This survey was carried out from January 1994 to January 1995 at six specialised
      cancer genetic clinics located in different parts of France Female consultands
      who were first degree relatives of cancer patients and who had at least one case
      of breast cancer in their family, affecting either themselves or a first degree
      relative or both, participated in this study. Among the 248 eligible consultands
      attending the clinics during the study period, 84.3% answered a post-consultation
      questionnaire. Among the 209 respondents, 40.7% (n = 85) were cancer patients and
      59.3% (n = 124) were healthy consultands. A high consensus in favour of genetic
      testing was noted, since 87.7% of the sample stated that they would ask for
      breast cancer gene testing if this test became available. The underlying
      assumption of 96.6% of the women was that their health surveillance would be
      improved after a positive test. A high awareness of the anxiety that would be
      generated in a family after a positive result was observed and found to be
      associated (p < 0.05) with the anxiety and depressive profiles of the patients.
      Half of the healthy respondents said they would not change their attitude towards
      screening if the results of predictive testing turned out to be negative. Only
      13.7% of the 161 patients who stated that the oncogeneticists asked them to
      contact their relatives firmly refused to do so, mainly because of difficult
      family relationships.

PMID- 8880572
TI  - Prediction of psychological functioning one year after the predictive test for
      Huntington's disease and impact of the test result on reproductive decision
      making.
AB  - For people at risk for Huntington's disease, the anxiety and uncertainty about
      the future may be very burdensome and may be an obstacle to personal decision
      making about important life issues, for example, procreation. For some at risk
      persons, this situation is the reason for requesting predictive DNA testing. The
      aim of this paper is two-fold. First, we want to evaluate whether knowing one's
      carrier status reduces anxiety and uncertainty and whether it facilitates
      decision making about procreation. Second, we endeavour to identify pretest
      predictors of psychological adaptation one year after the predictive test
      (psychometric evaluation of general anxiety, depression level, and ego strength).
      The impact of the predictive test result was assessed in 53 subjects tested,
      using pre- and post-test psychometric measurement and self-report data of follow
      up interviews. Mean anxiety and depression levels were significantly decreased
      one year after a good test result; there was no significant change in the case of
      a bad test result. The mean personality profile, including ego strength, remained
      unchanged one year after the test. The study further shows that the test result
      had a definite impact on reproductive decision making. Stepwise multiple
      regression analyses were used to select the best predictors of the subject's post
      test reactions. The results indicate that a careful evaluation of pretest ego
      strength, depression level, and coping strategies may be helpful in predicting
      post-test reactions, independently of the carrier status. Test result (carrier/
      non-carrier), gender, and age did not significantly contribute to the prediction.
      About one third of the variance of post-test anxiety and depression level and
      more than half of the variance of ego strength was explained, implying that other
      psychological or social aspects should also be taken into account when predicting
      individual post-test reactions.

PMID- 8880573
TI  - A recurrent mutation, ala391glu, in the transmembrane region of FGFR3 causes
      Crouzon syndrome and acanthosis nigricans.
AB  - Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have previously
      been identified in Crouzon syndrome, an autosomal dominant condition involving
      premature fusion of the cranial sutures. Several different missense and other
      mutations have been identified in Crouzon syndrome patients, clustering around
      the third immunoglobulin-like domain. We report here the identification of a
      mutation in the transmembrane region of FGFR3, common to three unrelated patients
      with classical Crouzon syndrome and acanthosis nigricans, a dermatological
      condition associated with thickening and abnormal pigmentation of the skin. The
      mutation within the FGFR3 transcript was determined by direct sequencing as a
      specific gcg to gag transversion, resulting in an amino acid substitution
      ala391glu within the transmembrane region.

PMID- 8880574
TI  - Clinical and genetic heterogeneity of hypochondroplasia.
AB  - Hypochondroplasia (HCH) is an autosomal dominant condition characterised by short
      stature, micromelia, and lumbar lordosis. In a series of 29 HCH probands (13
      sporadic cases, 16 familial cases), we tested their DNA for the N540K recurrent
      mutation previously described in the proximal tyrosine kinase domain of the FGFR3
      gene on chromosome 4p16.3, and we detected this mutation in 21/29 HCH patients.
      Interestingly, three familial cases were clearly unlinked to chromosome 4p16.3.
      Reviewing the clinical and radiological manifestations of the disease a
      posteriori, we observed that the N540K mutation was associated with relative
      macrocrania with a high and large forehead and short hands. By contrast, in the
      three pedigrees inconsistent with linkage to chromosome 4p16.3, the clinical
      phenotype was milder, macrocephaly and shortening of the long bones was less
      obvious, the hands were normal, and no metaphyseal flaring was noted. This study
      supports the view that HCH is a clinically and genetically heterogeneous
      condition.

PMID- 8880575
TI  - Genetic heterogeneity of Usher syndrome type II in a Dutch population.
AB  - The Usher syndromes are a group of autosomal recessive disorders characterised by
      retinitis pigmentosa (RP) with congenital, stable (non-progressive) sensorineural
      hearing loss. Profound deafness, RP, and no vestibular responses are features of
      Usher type I, whereas moderate to severe hearing loss and RP with normal
      vestibular function describe Usher type II. The gene responsible for most cases
      of Usher II, USH2a, is on chromosome 1q41; at least one other Usher II gene (as
      yet unlinked) is known to exist. Usher III presents with a progressive hearing
      loss that can mimic the audiometric profile seen in Usher II. A gene causing
      Usher III in a group of Finnish families, USH3, resides on chromosome 3q. Since
      the phenotypes for Usher II and III overlap, it is important to determine how
      frequently Usher IIa, Usher IIb, and Usher III occur in a clinical population of
      non-Usher I patients. DNA was collected from 29 Dutch families and genotyped with
      six DNA markers known to flank the USH2a gene closely, and with five markers that
      flank USH3. Results of haplotype and linkage analysis were consistent with
      linkage to the USH2a locus in 26 of these 29 Dutch families. Three families
      displayed no linkage to 1q41 markers, and one of these three families appeared
      unlinked to 3q markers as well; current haplotypes of the other two families are
      inconclusive for linkage with the USH3 locus without further genotyping. While an
      A test for heterogeneity of USH2a was statistically significant, no convincing
      evidence of linkage to USH3 was found in this Dutch sample. Consequently, the
      frequency of the unlinked variety of Usher IIa (Usher IIb) in The Netherlands was
      estimated as 0.104. To determine if marker alleles could be used to differentiate
      Usher type IIa from Usher IIb, parental chromosomes of the 26 Usher IIa families
      were analysed for significant non-random association of specific alleles from
      flanking loci with USH2a, but no linkage disequilibrium was observed in this
      Dutch population.

PMID- 8880576
TI  - A clinical severity grading scale for Marfan syndrome.
AB  - There is considerable interest in assessing patients with Marfan syndrome at the
      clinical, protein, and genetic levels. Clinical assessments are inconsistent
      between centres and between clinicians. There are no satisfactory clinical
      grading scales against which to analyse the molecular information, limiting the
      scope of clinical/ molecular correlations. We present grading scales for the
      major clinical systems involved in Marfan syndrome and suggest that their
      widespread use will facilitate collaborative approaches to clinical/ molecular
      correlations and international assessments of therapy.

PMID- 8880577
TI  - Double mutant fibrillin-1 (FBN1) allele in a patient with neonatal Marfan
      syndrome.
AB  - It is now well established that defects in fibrillin-1 (FBN1) cause the variable
      and pleiotropic features of Marfan syndrome (MFS) and, at the most severe end of
      its clinical spectrum, neonatal Marfan syndrome (nMFS). Patients with nMFS have
      mitral and tricuspid valve involvement and aortic root dilatation, and die of
      congestive heart failure, often in the first year of life. Although mutations in
      classical MFS have been observed along the entire length of the FBN1 mRNA,
      mutations in nMFS appear to cluster in a relatively small region of FBN1,
      approximately between exons 24 and 34. Here we describe the appearance of two
      FBN1 mutations in a single allele of an infant with nMFS. The changes were within
      six bases of each other in exon 26. One was a T3212G transversion resulting in an
      I1071S amino acid substitution and the second was an A3219T transversion
      resulting in an E1073D amino acid substitution. This is the first reported double
      mutant allele in FBN1.

PMID- 8880578
TI  - Rett syndrome, classical and atypical: genealogical support for common origin.
AB  - AIMS OF THE STUDY: By using genealogical methods in atypical females with Rett
      syndrome (RS) we looked for support for the assumption that atypical RS cases are
      true variants of classical RS. SUBJECTS: We selected from the Swedish national RS
      series the "milder" RS cases, 10 years of age and older, fulfilling the criteria
      for the "forme fruste" (FF) type of RS. For 32 FF cases we were able to carry out
      complete genealogical analyses on 61 parental lines. The pedigrees contained
      details of about 3200 ancestors. COMMON GEOGRAPHICAL ORIGINS: Eleven (34%) of the
      FF females could be traced to a previously defined "Rett area" and no fewer than
      six females had their origin in the same homestead as another previously examined
      classical RS patient. ANCESTRY: In four pedigrees, two each contained one FF and
      two classical RS and two each contained one FF and one classical RS, all 10 being
      descendants of the same four couples who lived several generations ago.
      CONSANGUINITY: Consanguinity in four grandparents (6.6% (SD 3.2%)) is probably a
      higher frequency than in the average Swedish population and supported our
      findings from a series of classical RS. TRANSMISSION: The data indicate that
      transmission starts with a premutation that over generations can result in a full
      mutation giving rise to RS. Both the X chromosomes and a pair of autosomes may be
      involved. CONCLUSION: Many, or most, atypical FF cases are true variants of RS.

PMID- 8880579
TI  - A duplication of distal Xp associated with hypogonadotrophic hypogonadism,
      hypoplastic external genitalia, mental retardation, and multiple congenital
      abnormalities.
AB  - An unusual familial case of three sibs with a partial duplication of distal Xp
      sequences is described. The proband, an 18 year old boy, showed mental
      retardation, severe dysmorphic features, hypogonadotrophic hypogonadism (HHG),
      and hypoplastic external genitalia. His karyotype was 46,Y,inv dup(X) (p22.11-->p
      22.32). The proband has two sisters each with the same inv dup(Xp) chromosome.
      Both sisters presented with short stature but were otherwise phenotypically
      normal. The abnormal X chromosome was inactive in the majority of cells examined.
      Southern blot dosage analysis indicated a duplication of distal Xp sequences. The
      proximal breakpoint is located between DXS28 and DXS41, and is therefore at least
      2 Mb distal to the DSS locus. The relationship between the phenotype and the Xp
      duplication is discussed.

PMID- 8880581
TI  - Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann
      Froboese syndrome).
AB  - Multiple endocrine neoplasia type 2B (MEN 2B), or the mucosal neuroma syndrome,
      is an autosomal dominant hamartoneoplastic syndrome. Features include multiple
      mucosal neuromas, phaeochromocytoma, medullary thyroid carcinoma, and Marfanoid
      body habitus with a characteristic dysmorphic facies. The gene responsible is the
      receptor tyrosine kinase (RET) proto-oncogene on chromosome 10. The mutational
      spectrum of MEN 2B is remarkably narrow, with over 95% of cases being caused by a
      single methionine to threonine substitution in the intracellular tyrosine kinase
      domain. Recent biochemical evidence suggests that this mutation alters the
      substrate specificity of intracellular signal transduction.

PMID- 8880580
TI  - Jacobsen syndrome: report of a patient with severe eye anomalies, growth hormone
      deficiency, and hypothyroidism associated with deletion 11 (q23q25) and review of
      52 cases.
AB  - We have evaluated a patient with Jacobsen syndrome. The patient presented with
      growth retardation, hypotonia, trigonocephaly, telecanthus, downward slanting
      palpebral fissures, bilateral inferior colobomas (of the iris, choroid, and
      retina), hydrocephalus, central nervous system (CNS) abnormalities, and an
      endocardial cushion defect, features commonly seen in Jacobsen syndrome.
      Endocrine evaluation showed growth hormone deficiency and central hypothyroidism.
      Chromosome analysis showed a 46,XX,del(11)(q23q25) de novo karyotype.
      Cytogenetically, the deletion appeared to include most of bands 11q23 and q24 and
      a portion of q25. Using chromosome specific paint probe, a combination of
      chromosome 11 centromere, telomere, and region specific cosmid probes from
      11q14.1-14.3, 11q23.3, and 11q24.1, we have localised the deletion breakpoint to
      q24.1. Phenotype-karyotype correlation of patients with Jacobsen syndrome and
      specific deletions of chromosome 11q has enabled us to suggest that the critical
      region for this syndrome lies in close proximity to cytogenetic band 11q24.
      Although growth retardation is a consistent finding in 11q deletion syndrome, the
      presence of hypothalamic-pituitary hormone deficiency has not been reported
      previously.

PMID- 8880582
TI  - Homozygous myotonic dystrophy: clinical and molecular studies of three unrelated
      cases.
AB  - We report the clinical and molecular study of three unrelated homozygous myotonic
      dystrophy patients. In the first family, the homozygous patient shows the
      classical form of the disease with two DM alleles of very different expansion
      sizes (1000 and 60 repeats). In the second family, the homozygous patient is
      mildly affected and carries a minimally expanded allele (64 repeats) and a
      "normal" allele (38 repeats) that increases in size when transmitted. Such an
      intergenerational expansion of an allele in this range of repeats has not been
      reported to date. The third homozygous case has late onset bilateral cataracts as
      the only symptom. She has two minimally expanded alleles (51 and 120 repeats)
      that showed different intergenerational enlargement during transmission to the
      next generation.

PMID- 8880583
TI  - Molecular basis of hereditary fructose intolerance in Italy: identification of
      two novel mutations in the aldolase B gene.
AB  - We screened the aldolase B gene in 14 unrelated Italian patients with hereditary
      fructose intolerance (HFI), and found two novel disease related mutations: a
      single nucleotide deletion in exon 2 (delta A20) that leads to an early stop
      codon, and a C-->T transition in exon 8 that substitutes an Arg with a Trp
      residue at codon 303 (R303W).

PMID- 8880584
TI  - Chromosome 3p23 break with ring formation and translocation of displaced 3p23-
      >pter segment to 6pter.
AB  - An 11 year old boy with short stature, learning difficulties, and no obvious
      facial anomalies has a ring (3)(p23q29) formed by a break in the short arm at
      3p23 and subsequent fusion with 3qter. A second rearrangement involving
      translocation of the displaced 3p23-->pter segment to chromosome 6 at 6pter is
      non-reciprocal with no obvious loss of distal 6pter material. The involvement of
      one chromosome in two separate rearrangements is uncommon. The patient's
      relatively mild phenotype appears to be associated with the "ring syndrome" and
      ring instability in division rather than from any segmental aneuploidy resulting
      from the presence of the two rearrangements.

PMID- 8880585
TI  - Diagnosis of a complex chromosomal rearrangement using fluorescent in situ
      hybridisation.
AB  - We report the use of fluorescent in situ hybridisation (FISH) to clarify a
      complex chromosomal rearrangement (CCR) carried by a woman presenting with
      recurrent miscarriages. CCRs are rare cytogenetic rearrangements involving three
      or more chromosomes, which can be difficult to interpret using routine
      cytogenetic studies with GTG banding. FISH was used to establish a correct
      interpretation of the maternal karyotype before amniocentesis in a present
      pregnancy.

PMID- 8880586
TI  - A 3 1/2 year old girl with distal trisomy 19q defined by FISH.
AB  - A 3 1/2 year old girl was evaluated because of developmental delay. Short stature
      was evident with height between the 3rd and 10th centiles, while weight and head
      circumference were on the 50th centile. Dysmorphic features consisted of a high
      bossed forehead, pointed short ear lobes, small nose, bilateral convergent
      strabismus, left simian crease, a gap between the first and second toes
      bilaterally, mild clinodactyly, and a broad, barrel shaped thorax. Cytogenetic
      investigations showed an unbalanced karyotype, 46,XX,10q+, which was de novo in
      origin. Fluorescence in situ hybridisation (FISH) using three library probes
      (from chromosomes 10, 19, and 19q) and a YAC probe (from 10q telomere) showed
      that the additional material on 10q was derived from chromosome 19q. The patient
      had an unbalanced translocation, 46,XX,-10,+der(10)t(10;19)(q26.3; q13.3), which
      resulted in distal trisomy 19q. Few other cases of proven distal trisomy 19q are
      available for comparison of clinical features.

PMID- 8880587
TI  - Non-expression of a common mutation in the 21-hydroxylase gene: implications for
      prenatal diagnosis and carrier testing.
AB  - Mutation analysis in the family of a child with 21-hydroxylase deficiency showed
      that the father and affected child were homozygous for a mutation, A/C655G,
      believed to activate a cryptic splice site in intron 2 of the 21-hydroxylase
      gene. The father, who was clinically asymptomatic, showed no biochemical evidence
      of disease. These results create problems for the management of future
      pregnancies in such families and for the interpretation of the risk associated
      with carrier status for this mutation.

PMID- 8880588
TI  - Evidence to exclude SOX9 as a candidate gene for XY sex reversal without skeletal
      malformation.
AB  - The skeletal malformation syndrome campomelic dysplasia (CMD1) is caused by
      mutations within the SOX9 gene or chromosomal rearrangement breakpoints outside
      SOX9. Approximately three quarters of cases of CMD1 in XY subjects show complete
      or partial sex reversal. As some mutations cause CMD1 alone and others cause CMD1
      and sex reversal, it is conceivable that some mutations might cause sex reversal
      in the absence of CMD1. In this study, we have investigated this possibility by
      screening the entire coding region of SOX9 in 30 patients with a spectrum of XY
      sex reversal phenotypes. No mutations were identified, suggesting that SOX9
      should not be considered a candidate gene for XY sex reversal without skeletal
      malformation.

PMID- 8880589
TI  - First report of CFTR mutations in black cystic fibrosis patients of southern
      African origin.
AB  - Cystic fibrosis (CF) is thought to be rare in the black populations of Africa who
      have minimal white admixture. Only a few cases have been reported but have not
      been studied at the molecular level. We report the detection of CFTR mutations in
      three southern African black patients. One was homozygous for the 3120 + 1G-->A
      mutation, while the other two were compound heterozygotes each with this mutation
      on one chromosome. The other mutations were G1249E and a previously unreported in
      frame 54 bp deletion within exon 17a involving nucleotides 3196-3249 (3196del54).
      The 3120 + 1G-->A mutation was first described in American black patients and has
      been shown to be a common mutation in this population (9-14% of CF chromosomes).
      It was also found in a black CF patient whose father, the 3120 + 1G-->A carrier,
      is from Cameroon. These data suggest that it is an old mutation which accounts
      for many of the CFTR mutations in African blacks.

PMID- 8880590
TI  - Psychological aspects of von Recklinghausen neurofibromatosis (NF1)

PMID- 8880591
TI  - The male excess in Down's syndrome.

PMID- 8880592
TI  - Predictive genetic testing in children.

PMID- 8880593
TI  - Medical futility and life-sustaining treatment decisions.

PMID- 8880594
TI  - Interrater reliability of the Glasgow Coma Scale.

PMID- 8880595
TI  - Pallidotomy: a surgical intervention for control of Parkinson's disease.
AB  - Parkinson's disease, a chronic incurable disorder, has a significant impact on
      quality of life. Parkinson's disease results from chronic degeneration of cells
      in the basal ganglia that produce dopamine. It typically affects elderly
      individuals producing muscle rigidity and akinesia. Traditionally, Parkinson's
      disease has been controlled by medications. However, for some patients,
      medications may no longer be effective, or may produce drug-related
      complications. For this group of patients, pallidotomy is gaining support as an
      intervention to control the debilitating symptoms of Parkinson's disease, thus
      enabling a person to perform everyday tasks. Although the procedure was developed
      in the 1950s, contemporary technology has allowed a resurgence of the
      intervention. With the focus on relief of two of the major symptoms of
      Parkinson's disease, the pallidotomy procedure is gaining support as a surgical
      intervention for this disease. Therefore, it is important for the health care
      team to have an understanding of the disease process, surgical intervention and
      postoperative care to enhance quality outcomes for this patient population.

PMID- 8880596
TI  - A look at recent hyperventilation studies: outcomes and recommendations for early
      use in the head-injured patient.
AB  - During the past decade, mounting controversy surrounding the use of
      hyperventilation for the treatment of head injury has raised concerns about its
      safety and therapeutic benefits. A recent investigation of the medical literature
      was conducted to determine if outcomes for the head-injured patient continued to
      support the use of indiscriminate, and often unmonitored, hyperventilation in the
      pre-hospital and early hospital phases of care, and to determine if current
      investigators are recommending the use of hyperventilation for the initial
      treatment of all unconscious head-injured patients. Findings suggest that head
      injured patients in the pre-hospital and early phases of care are at increased
      risk for suffering hyperventilation-induced secondary brain injury. Current
      researchers are now recommending a highly monitored, cautions and selective
      approach to care; this approach calls our current practice into question.

PMID- 8880597
TI  - Challenges in patient and family care following an unsuccessful suicide attempt.
AB  - According to the dictionary, challenge is a stimulating or interesting task or
      problem. But neuroscience nurses can offer a more comprehensive definition,
      especially in the context of caring for a patient and their family after an
      unsuccessful suicide attempt. This situation stimulates our thinking about why
      individuals try to take their lives, how suicide is attempted and what we, as
      nurses, can do to turn a hopeless situation into one of hope.

PMID- 8880598
TI  - Health care management of children with cognitive and physical disabilities: to
      treat or not to treat.
AB  - Advanced medical technology has provided life support and maintenance for high
      risk infants. In dramatically increasing numbers, children surviving aggressive
      intervention as neonates and infants suffer from varying degrees of physical and
      mental disability. Once these children are stable and grow older difficult
      medical intervention decisions need to be made. As nurses, we are often in
      situations involving difficult treatment decisions made by the family and health
      care team. We need to be aware of our personal beliefs and ethical principles to
      effectively support family members and participate in decision making. Ethical
      principles serve as a guide to the decision making process.

PMID- 8880600
TI  - Hope facilitating strategies for the family of the head injury patient.
AB  - Approximately 200 new head injuries are reported per 100,000 population each year
      in the United States. These injuries are more common in younger men and caused
      most frequently by motor vehicle accidents. Head injuries occur suddenly and
      unexpectedly. Head injury affects not only the individual but the family as well.
      The family's functional abilities are threatened by the head injury of a family
      member. The family's adaptation to head injury and life-threatening events
      surrounding the injury has a significant impact on the patient's rehabilitation.
      A family's response of denial or lack of hope in the future has been identified
      as a major obstacle to successful adaptation. The hopeless family may be unable
      to make necessary changes at home or learn important aspects of the patient's
      care. Depending upon the extent of the head injury, the family needs to know that
      most head trauma patients make significant progress in the first six months.
      Progress usually continues, less dramatically, for the next two to three years.

PMID- 8880599
TI  - The benevolent overreaction: nursing assessment and intervention in families
      coping with seizure disorder.
AB  - Boone and Hartman identified the phenomenon of benevolent overreaction to
      describe the enmeshment seen in parents and their chronically ill children. The
      cylce of the benevolent overreaction begins with the child's diagnosis with a
      chronic illness and the subsequent natural protective behaviors of the parents.
      However, overprotection may become pathologic if these protective behaviors
      persist and delay or prevent the child's achieving developmental goals. This ego
      boundary deficit is one of the most frequently seen phenomena in families with
      chronically ill children. On the Comprehensive Epilepsy Unit this phenomenon was
      repeatedly observed. The purpose of this investigation was to ascertain the
      frequency of benevolent overreaction seen on the unit, and to identify the
      nursing interventions used to address this issue. A chart review was used to
      identify the frequency of the phenomenon during the past year, the discipline
      first identifying the phenomenon and nursing interventions applied to the
      phenomenon. Nursing staff interviews were then conducted, using unit census
      records of the past year, to identify staff recall of the phenomenon. Nursing
      staff frequently identified the components of benevolent overreaction in the
      inpatient population, however, consistent intervention for the phenomenon was
      less frequently seen. Autonomy, empowerment and self-advocacy for families are
      goals of the Comprehensive Epilepsy Unit. Consistent application of the nursing
      process to this phenomenon is vital to providing quality patient care.

PMID- 8880601
TI  - Refusal of food and water by a man with end stage Parkinson's disease.
AB  - In the future, we need to consider the social and financial implications of
      allowing someone to remain in an acute care hospital for comfort care until
      death. Other acceptable options for the non-terminal but, severely disabled
      patients must be identified so that we are able to respect and honor our
      patients' autonomous decisions without using the increasingly scarce health care
      resources. While not all ethical dilemmas of this nature will be resolved in such
      a relatively uncomplicated manner, this situation does provide us with a
      foundation from which to approach future cases. We have learned to listen closely
      to our patients; we have learned the importance of understanding who our patients
      were and who they are now; we have learned from Mr. K's strength to express his
      convictions.

PMID- 8880602
TI  - RNFA: cost effective health care providers.

PMID- 8880603
TI  - Flavinoids, vitamins and stroke.

PMID- 8880604
TI  - Use of positron emission tomography in diagnosing Alzheimer's disease.

PMID- 8880605
TI  - Vaccine for brain tumors?

PMID- 8880606
TI  - Rilutek (Riluzole) may extend survival in amyotrophic lateral sclerosis.

PMID- 8880607
TI  - Effects of methylprednisolone on lesioned and uninjured mammalian spinal neurons:
      viability, ultrastructure, and network electrophysiology.
AB  - An in vitro investigation was undertaken to provide information regarding the
      effectiveness of methylprednisolone sodium succinate (MPSS) as a treatment for
      the primary mechanical injury of spinal cord (SC) trauma. Exposure of uninjured
      mouse SC cells to MPSS for 24 h caused neuronal stress when the concentration
      exceeded 150 micrograms/mL; neuronal death occurred at concentrations above 600
      micrograms/mL. The concentration range for MPSS protection of SC neurons
      subjected to a defined physical injury (laser microbeam transection of a primary
      dendrite 100 microns from the perikaryon) was very narrow: survival in the 30
      micrograms/mL group differed significantly from the untreated control group
      (68.5% +/- 14.1 vs. 47.1% +/- 14.1), treatment with 20 or 60 micrograms/mL MPSS
      did not increase survival, and treatment with 100 micrograms/mL MPSS accelerated
      ultrastructural deterioration and increased the likelihood of death. Enhanced
      survival of lesioned neurons was observed when 30 micrograms/mL MPSS was applied
      within 15 min of dendrotomy but not when MPSS was administered 2 h after
      lesioning. Multimicroelectrode plate (MMEP) studies of SC network electrical
      activity indicated that MPSS associated readily with neuronal membranes. This
      finding was consistent with the hypothesis that MPSS may protect lesioned neurons
      by stabilizing damaged membranes, enhancing lesion resealing, and limiting the
      spread of ion-mediated damage. However, comparisons of neurite die-back 24 h
      after dendrotomy found no significant difference between MPSS-treated and control
      neurons. Application of 30 or 100 micrograms/mL MPSS increased the spontaneous
      burst activity of SC networks grown on MMEPs, however, there was no evidence that
      the increased excitability at these concentrations was the result of specific
      actions of MPSS on GABA or NMDA synapses.

PMID- 8880608
TI  - Detection of impaired cerebral autoregulation using spectral analysis of
      intracranial pressure waves.
AB  - Successful resuscitation following severe traumatic brain injury (TBI) requires
      rapid evaluation of intracranial pressure (ICP), cerebrovascular reactivity
      (autoregulation), and cerebral metabolism. During impaired autoregulation,
      inadequate cerebral blood flow (CBF) can lead to ischemia while excessive CBF can
      result in elevated ICP. Without information regarding the state of
      autoregulation, treatment of either situation may ameliorate one problem but
      exacerbate the other. It has been hypothesized that fast Fourier transform (FFT)
      analysis of arterial blood pressure (BP) and ICP waves can differentiate states
      of intact and impaired autoregulation. BP and ICP waves were recorded in canines
      before and after ischemic injury during arterial normotension, hypertension, and
      hypotension induced with dopamine or nitroprusside infusion. Transfer functions
      (TFn) were calculated from FFT spectra as ratios of ICP and BP harmonic peak
      amplitudes to distinguish states of vasoreactivity. During normotension and
      hypertension, autoregulation was intact and TF1 averaged 0.05. During
      hypotension, TF1 averaged 0.22 (8 x baseline, p < 0.010). During impaired
      autoregulation following ischemic injury, TF1 averaged 0.50 (18 x baseline, p <
      0.010; 2 x nitroprusside levels, p < 0.01). This large difference in TF relative
      to baseline extended over a large range of BP (60 < BP < 180 mm Hg). Based on
      these data and previous results, it was estimated that TF can differentiate
      impaired autoregulation from effects solely related to elevated ICP or active
      vasodilation for ICP < 30-40 mm Hg. This suggests that for specific, but widely
      applicable physiologic conditions, spectral analysis can identify states of
      impaired autoregulation and, as an adjunct to traditional monitoring techniques,
      aid in acute resuscitation and prevention of secondary injury in TBI.

PMID- 8880609
TI  - Effects of traumatic brain injury on the cholinergic system in the rat.
AB  - Rats subjected to a mild to moderate fluid percussion injury exhibit memory
      deficits that are similar to rats that have received lesions of the
      septohippocampal system. Because the cholinergic system plays a major role in
      septohippocampal function, we studied the kinetics of the synthetic enzyme for
      acetylcholine, choline acetyltransferase (ChAT), at 1 h, 24 h, or 5 days after a
      fluid percussion injury. Decreases in ChAT activity were found in the dorsal
      hippocampus (25%), frontal (32%), and temporal (23%) cortices 1 h after injury.
      In the parietal cortex, a greater than 50% increase in ChAT activity was observed
      at all time intervals assessed. At 5 days after TBI, there was an 18% increase in
      ChAT activity in the medial septal area. These data provide evidence that a mild
      to moderate fluid percussion injury produces changes in the cholinergic system in
      brain areas related to memory.

PMID- 8880610
TI  - Changes in local microvascular permeability and in the effect of intervention
      with 21-aminosteroid (Tirilazad) in a new experimental model of focal cortical
      injury in the rat.
AB  - In a new, reproducible model of rodent focal cortical injury, we have shown that
      in the absence of early traumatic disruption of the microvasculature and
      subsequent hemorrhage, delayed perivascular protein leakage and polymorphonuclear
      leukocyte infiltration of the injured cortex occur. In this study we employed a
      sensitive quantitative autoradiographic technique (using alpha-aminoisobutyric
      acid as a tracer) to investigate the focal changes in microvascular permeability
      with time and to determine the effects of administration of a 21-aminosteroid
      (Tirilazad) initiated 5 min after induction of the cortical injury. At all time
      points studied, there was a significant increase in perilesional blood-brain
      barrier permeability in lesioned animals treated with vehicle, compared to
      shamoperated animals, with the most marked increase in blood-brain barrier
      permeability at 4 h postinjury (mean Ki +/- SE = 19.2 +/- 2.4/1000 min with
      cortical injury, 1.5 +/- 0.3/1000 min in shams) (mean volume +/- SE = 15.48 +/-
      0.7 mm3). In animals with cortical injury treated with Tirilazad (10 mg/kg),
      there was a significant reduction in microvascular permeability at the site of
      injury (Ki = 3.1 +/- 0.5, p < 0.001) and a significant reduction in volume of
      increased permeability (4.86 +/- 0.7 mm3, p < 0.01) at 4 h postinjury. In this
      model of cortical injury, a delayed increase in microvascular permeability
      occurs, which is significantly attenuated by postinjury treatment with Tirilazad.

PMID- 8880611
TI  - Evaluation of a carbohydrate-free diet for patients with severe head injury.
AB  - Hyperglycemia, which may be caused or exacerbated by conventional diets, may
      worsen the neurological outcome from severe head injury, especially if secondary
      ischemic insults occur. The purpose of this study was to evaluate an experimental
      diet intended to replace systemic caloric and protein requirements without
      producing hyperglycemia. In initial studies in the laboratory, 5 experimental
      diets were employed in a middle cerebral artery temporary occlusion model. The
      effects of the diets on blood biochemistry and on infarction volume were compared
      in fasted animals and in animals fed a control diet. Animals fed the experimental
      diets had a significantly lower preischemia blood glucose concentration, a higher
      blood concentration of ketone bodies, and a smaller infarct volume than the
      animals fed a control diet. One diet chosen from the laboratory study was then
      evaluated in a clinical study as a randomized, open-label trial. Twenty severely
      head-injured patients were randomly assigned to be fed the experimental diet, EN
      9305, or the control diet, Osmolyte HN, for the first 2 weeks after injury. Both
      treatment groups had similar blood glucose concentrations, averaging 6.33 +/-
      0.21 mumol/mL (114 +/- 4 mg/dL), on day 1 prior to starting the assigned diet.
      Blood glucose concentration increased in the control diet group to a peak of 8.37
      +/- 0.94 mumol/mL (151 +/- 17 mg/dL) on day 7 as the infusion rate of the diet
      was increased to the final rate. In the experimental diet group, the blood
      glucose concentration remained unchanged from fasting levels as the diet was
      advanced. Blood lactate concentration was lower, and blood ketone body
      concentrations were higher in the patients fed the experimental diet. Urinary
      nitrogen balance was better in the experimental diet group, but measures of
      visceral protein sparing, including serum albumin, plasma retinol binding
      protein, and total lymphocyte count, were not significantly different in the 2
      treatment groups. Measures of cerebral anaerobic metabolism, including CSF
      lactate concentration and cerebral lactate production, were not significantly
      different in the 2 treatment groups. These studies suggest that a carbohydrate
      free diet such as EN-9305 might have advantages for patients with severe head
      injury by replacing systemic caloric and protein requirements without producing
      hyperglycemia.

PMID- 8880612
TI  - Posterior superior oblique tenectomy at the scleral insertion for collapse of A
      pattern strabismus.
AB  - PURPOSE: To evaluate the efficacy of tenectomy of the posterior fibers of the
      superior oblique tendon at the scleral insertion to reduce A-pattern deviations
      with mild-to-moderate superior oblique overaction. METHODS: We retrospectively
      reviewed 22 consecutive patients with A-pattern strabismus and mild-to-moderate
      superior oblique overaction on whom posterior tenectomy of the superior oblique
      at the scleral insertion was performed between January 1988 and August 1994. Nine
      females and 13 males were included, with an age range of 3 to 36 years (mean 13.0
      years). RESULTS: The average preoperative A-pattern for all patients was 18.0
      prism diopters (delta) (10 to 33 delta), and a collapse of 16.1 delta was
      achieved (P < .000001). The average preoperative A-pattern for esotropic patients
      was 21.0 delta with an average correction of 18.6 delta. The average preoperative
      A-pattern for exotropic patients was 16.2 delta with a mean improvement of 14.5
      delta. Twenty patients (91%) were postoperatively measured to have 6 delta or
      less difference between up and downgaze. Follow up ranged from 5.0 to 41.0 months
      (average, 14.0 months). CONCLUSIONS: This technique provides the surgeon with a
      predictable partial superior oblique weakening operation that carries a low risk
      of induced superior oblique palsy, unwanted cyclotorsion, or head tilt.

PMID- 8880613
TI  - Conservative treatment of congenital dacryocele.
AB  - PURPOSE: To study prospectively the effectiveness of medical management of
      congenital dacryoceles. METHODS: All patients presenting with congenital
      dacryocele that were not infected were treated with warm compresses, massage, and
      topical antibiotics. Dacryoceles that did not resolve with at least two weeks of
      medical management were probed. Dacryoceles that were infected were treated with
      intravenous (IV) antibiotics in addition to warm compresses and massage. RESULTS:
      Seventeen patients with 21 dacryoceles were studied over a 3 1/2-year period. All
      patients were examined by the authors and treatment was initiated prior to 3
      weeks of age. Sixteen dacryoceles resolved with medical management in 1 to 6
      days. Three of these 16 dacryoceles were infected and patients were hospitalized
      at the time of initial ophthalmic evaluation (2 to 4 days of life). One
      additional dacryocele became infected after 2 days of medical management (4th day
      of life), requiring hospital admission and IV antibiotics. All four infected
      dacryoceles resolved within 24 hours of the initiation of IV antibiotics, warm
      compresses, and massage. Five dacryoceles were probed after not resolving within
      14 to 31 days of medical management. One dacryocele required a repeat probing.
      CONCLUSIONS: Medical management can be effective in the treatment of congenital
      dacryoceles; 76% of dacryoceles in this series resolved after 6 days of medical
      management.

PMID- 8880614
TI  - Pediatric Devic's neuromyelitis optica.
AB  - PURPOSE: Neuromyelitis optica (Devic's disease) is a rare clinical syndrome of
      unilateral or bilateral optic neuritis (ON) and transverse myelitis (TM)
      occurring within an 8-week time interval. All reports mainly involve adults and
      describe a poor neurologic and ophthalmic clinical course without specific
      attention to their few pediatric cases. The purpose of this study was to develop
      a clinical profile in the pediatric population. METHODS: A retrospective chart
      review over 15 years revealed nine cases of neuromyelitis optica. A literature
      search was undertaken and all cases of pediatric neuromyelitis optica were
      tabulated and analyzed separately. RESULTS: The average age of onset was 7 years
      with a preceding viral prodrome in all patients. The optic neuritis was bilateral
      in eight of nine patients (89%). Visual loss ranged from 20/30 to light
      perception. Moderate anterior disc edema was seen in all 17 affected eyes. The
      clinical course was characterized by a rapid visual and neurologic recovery. The
      average follow up was 5.3 years, with five patients followed for 6 years or
      longer. None of the nine patients had any visual or neurologic recurrence or
      other significant subsequent illness. Visual system follow up showed 20/20 in
      each eye of all patients with mild optic atrophy, identified in 47% of eyes.
      CONCLUSIONS: Devic's neuromyelitis optica occurs in the pediatric population as a
      distinct clinical entity with an excellent prognosis for visual and systemic
      recovery and no future recurrence or long-term sequelae.

PMID- 8880615
TI  - Corneal diameter in childhood aphakic glaucoma.
AB  - BACKGROUND: Glaucoma occurring after successful cataract surgery in infancy and
      childhood requires persistence to establish timely diagnosis and presents a
      therapeutic challenge. Previous studies have sought to identify risk factors,
      which would alert the clinician for the likelihood of developing glaucoma after
      cataract surgery in the young patient. Some risk factors are early age of
      surgery, microcornea, poor pupillary dilation, retained lens cortex, coexisting
      ocular anomalies, and cataract type. Other studies did not find these
      associations. In our experience, the majority of young aphakic glaucoma patients
      have microcornea. This study was carried out to investigate this association.
      METHODS: The records were reviewed of all patients treated for aphakic glaucoma
      between 1991 and 1995 to determine the age at cataract surgery, age at glaucoma
      surgery, age at glaucoma diagnosis, corneal diameters, and other clinical
      characteristics. RESULTS: Forty-eight eyes in 29 patients were identified with
      aphakic glaucoma. Forty-five of the 48 (94%) eyes were found to have microcornea
      when compared with the normal corneal diameter for their age. CONCLUSION: All
      children undergoing cataract surgery should have their corneal diameters
      recorded. Patients with corneal diameters smaller than normal should be followed
      closely for the development of glaucoma throughout childhood and beyond.

PMID- 8880616
TI  - Second Generation Binocular Polaroid Test.
AB  - BACKGROUND: The aim of the study was to introduce a new test to detect small
      areas of suppression in the binocular visual field and to lower the minimum age
      at which a suppression test could be identified correctly. Two tests were
      compared: the Binocular Polaroid Test (poltest), introduced in clinical practice
      a few years ago and used in screening programs for vision impairment; and the
      Second Generation Binocular Polaroid Test (polstar), more recently designed to
      have simpler answers than the poltest. METHODS: One hundred and eighty-two
      children were examined consecutively. To assess the validity of the two tests,
      sensitivity, specificity, predictive value, and phi coefficient were calculated.
      The applicability of the two tests and the speed of the responses was assessed by
      means of the test of probability of binomial distribution. RESULTS: The polstar
      has appeared to be simpler and easier in younger patients (age range 20 to 36
      months, P = 0.078), and has shown 100% of specificity with a sensitivity of 84%
      for the polstar 1 and of 100% for the polstar 2. CONCLUSION: The results appear
      to demonstrate that the poltest has been improved, and that the polstar may be
      considered an interesting investigation device for early detection of monocular
      visual impairment.

PMID- 8880617
TI  - Automated analysis of electromyographic (EMG) recordings during botulinum
      injections.
AB  - PURPOSE: Botulinum toxin is injected into extraocular muscles using
      electromyographic (EMG) guidance to confirm needle location prior to injection.
      The purpose of this study was to develop and test an automated, objective method
      of storing and grading EMG signal quality obtained during botulinum injection. A
      reliable, nonsubjective estimate of signal quality will enhance future studies of
      the complications or effectiveness of botulinum toxin injections into extraocular
      muscle. METHODS: Injections were administered using a standard procedure. The EMG
      was digitized, recorded, and analyzed using discrete Fourier transform and power
      spectrum analysis. Audible signal quality was also graded subjectively by the
      surgeon. Patients were followed to determine the clinical response to the
      injection. RESULTS: Eighteen patients (24 injections) were studied. Each sample
      was collected and analyzed in less than one second. The EMG contained signals
      over a range of frequencies from 50 to 500 Hz, with an average peak near 90 Hz.
      Substantial variability of the signal was observed between patients. Contracting
      muscle had a higher total power and peak frequency in most, but not all, cases.
      Total signal power correlated moderately with subjective estimates of signal
      quality. Neither subjective nor computer-derived signal quality estimates
      correlated with the response to injection or complications. CONCLUSIONS:
      Computerized signal analysis can automatically characterize EMG signal power and
      frequency distribution. Although this technique has the potential to identify
      needle location at the time of botulinum injection accurately, signal variability
      limited the clinical and research utility of the present protocol.

PMID- 8880618
TI  - Extraocular muscle fiber morphometry following combined recession-resection
      procedures in rabbits.
AB  - PURPOSE: In earlier studies, we have reported extraocular muscle fiber atrophy
      following recession and fiber hypertrophy following resection of a horizontal
      rectus muscle. Changes seen in the operated muscle were mirrored in the
      antagonist and were thought to be a compensatory response to sustained changes in
      tension across the muscle pair caused by the surgery and by changes in the
      rotational position of the globe. The purpose of this study is to examine the
      effects of combined recession-resection on extraocular muscle fiber diameter.
      METHODS: In 16 anesthetized rabbits, a 6-mm recession of the medial rectus was
      combined with a 6-mm resection of the lateral rectus in the left orbit. The
      horizontal rectus muscles were removed from both orbits of four rabbits at 2-, 4
      , 8-, and 16-week postoperative intervals. Cross-sections were cut from the
      midbelly of each muscle, and muscle fiber diameters were measured with a
      computerized morphometry unit. Mean fiber diameters from the operated orbit of
      animals at each postoperative interval were pooled and compared with means from
      the unoperated orbit using the paired-samples t test. RESULTS: No statistically
      significant change in fiber diameter was seen in either the global or orbital
      fiber layers at any postoperative interval examined. CONCLUSIONS: Because
      resection would be expected to increase and recession to decrease the resting
      tension across an agonist-antagonist pair, our results suggest that a combined
      recession-resection yields no significant net change in resting tension, and
      minimizes compensatory changes in extraocular muscle fiber diameter.

PMID- 8880619
TI  - The range and variability of ophthalmological parameters in normal children aged
      4 1/2 to 5 1/2 years.
AB  - BACKGROUND: Some standards for childhood ophthalmological variables exist.
      However, for most parameters, the range of variation found in normal children
      remains poorly defined. METHODS: We have determined the range of normal function
      for a number of commonly measured ophthalmological variables in 162 children,
      classified normal by Gold Standard ophthalmological examination. This group is
      representative of almost 12,000 normal children aged 4 1/2 to 5 1/2 in Nova
      Scotia. RESULTS: In 56.8% of eyes the visual acuity was 6/4.5. The use of a chart
      with crowding bars was more discriminating between differences in higher levels
      of acuity and highlighted differences in acuity between the two eyes. Randot
      stereoacuity showed a uniform, non-Gaussian distribution of scores. Cycloplegic
      refractive errors were distributed about a modal value of between +0.5 and +1.0
      diopter. Forty percent of eyes had no detectable astigmatism. Ninety-seven
      percent of subjects had no heterophoria. Fusional vergence data are presented.
      CONCLUSION: Our results document the complete normal range for selected
      ophthalmological parameters in normal preschoolers. The values obtained were in
      general better than expected.

PMID- 8880620
TI  - Axial length estimation in strabismic patients.
AB  - BACKGROUND: Previous studies have indicated that axial length determination is
      important in strabismic patients for defining the limit for a safe maximum
      recession of the medial rectus. Also, the response to strabismus surgery may be,
      in part, a function of axial length. We previously published a formula for
      predicting axial length based on age and refractive error; however, its accuracy
      has not been tested in a patient population that is different from the one used
      to generate the formula. The purpose of this study is to test a formula for
      estimating axial length, given age and refractive error, in a population that is
      different from that from which it was generated. METHOD: We measured axial length
      using A-scan ultrasonography in 163 consecutive patients undergoing strabismus
      surgery. Twenty-nine patients were younger than 18 months of age; 134 patients
      were between 18 months and 10 years of age. We compared the measured axial length
      determination with the axial length value estimated by a formula generated from
      our previous published series. RESULTS: For patients younger than 18 months of
      age, the equation estimated axial length within 0.5 mm in 41.4% of patients,
      within 1.0 mm in 79.3% of patients, and within 1.5 mm in 93.1% of patients. For
      patients between 18 months and 18 years of age, the formula estimated axial
      length within 0.5 mm in 37.3% of patients, within 1.0 mm in 73.1% of patients,
      and within 1.5 mm in 87.3% of patients. CONCLUSIONS: The formula may be useful
      for the strabismus surgeon in estimating axial length when A-scan ultrasonography
      is not available in an operating room setting, particularly in congenital
      esotropes who require larger recessions in small eyes. If, however, A-scan
      ultrasonography is available, it is preferable to using the formula. The formula
      is not sufficiently accurate for use for calculating intraocular lens power.

PMID- 8880621
TI  - Intraorbital cerebellar heterotopia associated with Chiari I malformation.

PMID- 8880622
TI  - Dry eye syndrome associated with Urbach-Wiethe disease.

PMID- 8880623
TI  - Intraocular Ki-1 lymphoma in a 2-year-old boy.

PMID- 8880626
TI  - Screening for retinopathy of prematurity.

PMID- 8880624
TI  - Earlier "surgical management of nontraumatic ectopic lenses".

PMID- 8880625
TI  - Color vision testing in young children.

PMID- 8880627
TI  - The first three weeks assessed by transvaginal color Doppler.
AB  - Transvaginal color Doppler has made possible to study ovarian and uterine
      perfusion in non-pregnant and pregnant patients, thus advancing the understanding
      of the early human development. RI of follicular blood flow starts decreasing
      prior to ovulation reaching its nadir at ovulation. It is considered that apart
      from hormonal factors the angiogenesis is also involved. The mature corpus luteum
      shows increased blood flow velocity in relation to preovulatory follicle.
      Comparing RI values of luteal blood flow of normal and ectopic pregnancy no
      difference was found. But in threatened, incomplete and missed abortions the
      resistance and pulsatility indices were significantly higher than in normal
      pregnancy. The follow up of the luteal flow might have a prognostic value in a
      group of patients with threatened abortion. In women with spontaneous cycles the
      day preceding the ovulation impedance to uterine flow velocity starts decreasing.
      Alterations in flow velocity patterns of the radial and spiral arteries in
      spontaneous ovulatory cycles are paralleling blood flow dynamics of the uterine
      arteries. In stimulated cycles RI increases the day before ovulation in both the
      uterine arteries and their branches. It seems that endometrial perfusion presents
      more accurate noninvasive assay of uterine receptivity than uterine artery
      perfusion alone. Endometrial receptivity is maximum during the time of peak
      luteal function during which implantation is most likely to occur. During the
      pregnancy impedance to blood flow decrease from the main uterine to the spiral
      arteries as well as with the advancing gestational age. The spiral arteries in
      pregnancy become the vessels with completely different haemodynamic
      characteristics in relation to other arteries of uteroplacental circulation.
      Color Doppler adds new information on perfusion and pathophysiological changes
      connected with the ectopic trophoblast implantation.

PMID- 8880628
TI  - Antepartum surveillance in preterm rupture of membranes.
AB  - The objective of this presentation is to describe noninvasive techniques of
      antepartum fetal assessment which allow the differentiation of  fetuses who will
      benefit from remaining in-utero versus those who are at risk for intraamniotic
      infection and will benefit from your prompt delivery. The literature is reviewed
      in regard to the fetal biophysical profile, the effect of premature rupture of
      membranes (PROM), the usefulness of individual biophysical component in
      predicting intraamniotic infection (amniotic fluid volume, non-stress testing),
      the use of the fetal biophysical profile in improving pregnancy outcome, the
      relationships among umbilical artery velocimetry, fetal biophysical profile and
      intraamniotic infection and the mechanisms by which infection diminishes fetal
      biophysical activities in PROM. After reviewing our own as well as the published
      experience with the use of fetal biophysical assessment in patients with PROM,
      the following conclusions are suggested: a) most studies have shown strong
      correlation between abnormal biophysical assessment and infection outcome
      (maternal and/or neonatal infection) as well as intraamniotic infection, if there
      is frequent (i.e. daily) testing; and b) fetal biophysical tests (profiles, NSTs,
      amniotic fluid volume determinations) are quite reliable in predicting the well
      fetus who can safely remain in-utero and also the fetus who is at high risk for
      developing neonatal sepsis. A protocol for management of preterm PROM will be
      outlined based upon frequent (daily) fetal biophysical assessment. Although there
      are no controlled randomized trials to support that pregnancy outcome is improved
      by the use of frequent biophysical assessment, non-randomized studies as well as
      studies with historic controls suggest that the use of frequent biophysical
      assessment is beneficial in managing patients with PROM.

PMID- 8880629
TI  - Doppler velocimetry of different sections of the fetal middle cerebral artery in
      relation to perinatal outcome.
AB  - To assess the standard curves of pulsatility index (PI) in different segments of
      middle cerebral artery (MCA): initial segment (MI) and subcortical segment (M2);
      to determine the variation of the flow velocity waveforms (FVW) of the M1 and M2
      segments of MCA in presence of fetal distress and to establish the possible
      correlation between the two segments of MCA. 50 normal pregnancies from 25 weeks
      of gestation to term and 20 pregnancy with alteration of fetal growth rate were
      investigated with serial records of the FVW of the M1 and M2 segments of the MCA
      and of the umbilical artery (UA) with a colour Doppler system. Severe fetal
      distress was associated to cerebral-placental ratio below 1 (C/P < 1). The
      perinatal outcome was established on the basis: 1) abnormal intrapartum CTG, 2)
      emergency cesarean section, 3) Apgar score at 1st and 5th minute after birth and
      4) birth eight centiles. In normal pregnancy P1 of M2 was always higher than that
      of M1: therefore M2/M2 resulted below 1, with a maximum peak near 32 weeks of
      gestation. In presence of moderate fetal distress only P1 of M2 was reduced
      (M1/M2 > 1). It exists a significant difference of PI in M1 and M2 segments of
      fetal MCA during gestation: thus MCA so it is important to identify the tract of
      fetal MCA when recording its FVW. Moreover we suppose that an initial "cerebral
      sparing" effect exists in order to protect the cortex by the initial hypoxic
      injury: this is shown by a M1/M2 > 1. The progression of fetal distress results
      in a greater haemodynamic modification, the so called "brain sparing" which is
      usually present when C/P < 1.

PMID- 8880630
TI  - Antenatal and postnatal treatment of pleural effusion and extra-lobar pulmonary
      sequestration.
AB  - An infant is reported who was identified antenatally to have an extralobar
      sequestration and a pleural effusion. Chronic drainage of the effusion was
      achieved by placement of a pleuroamniotic shunt. After delivery the infant
      underwent several thoracocenteses and then definitive surgery to remove an
      extralobar sequestration. The postnatal course was documented by lung function
      measurements.

PMID- 8880631
TI  - Tissue plasminogen activator and plasminogen activator inhibitors of type 1 and
      type 2 in the plasma of parturient women.
AB  - Changes in the fibrinolytic system of parturient women have so far been only
      partially documented. Our main questions were whether and how the concentration
      of tissue plasminogen activator (tPA) and plasminogen activator inhibitors of
      type 1 (PAI-1) and type 2 (PAI-2) change in the plasma throughout normal labor.
      The study group consisted of 38 women with normal pregnancy, delivering at term.
      The concentration of antigens tPA, PAI-1 and PAI-2 in plasma was tested by enzyme
      linked immuno-sorbent assay method, and the activity of PAI-1 by plasmin method.
      Results were analysed statistically. During labor the level of tPA antigen
      increases over two times: from 9.3 +/- 4.3 ng/ml before labor, to 23.3 +/- 9.6
      ng/ml in the second stage of labor. Changes of PAI-1 antigen as well as its
      activity though noticeable, were not statistically significant. PAI-2 antigen
      level increased significantly in the third stage (146.3 +/- 58.7 ng/ml before
      labor, and 212.2 +/- 75.0 ng/ml after placenta expulsion). In summary the more
      significant change in the fibrinolytic system during labor is an increase of the
      level of tPA and PAI-2 antigens, but their peaks appear in different stages of
      labor. The predominance of PAIs over tPA is maintained throughout the whole
      labor, though on a lower level as can be inferred from the tPA/PAIs ratio.

PMID- 8880632
TI  - Umbilical vein oxygen tension independent from gestational age at birth.
AB  - Umbilical venous oxygen tension (UVPO2) and gestational age are negatively
      correlated antepartum. To see if the negative correlation between UVPO2 and
      gestational age would still be present postpartum, a retrospective study of all
      7522 births at the University of Zurich Hospital from 1989 through 1992 was
      performed. The 6612 infants with UVPO2 values were divided into low and higher
      risk groups. Singletons between the 10th and 90th weight percentiles, born
      vaginally with cephalic presentation after spontaneous onset of labor from
      healthy mothers were considered low risk. All other births were considered higher
      risk. No correlations between UVPO2 and gestational age were found in any group
      studied (low risk, higher risk or total population). The higher risk group had a
      lower mean UVPO2 than the low risk group (p < .0001). Since there is a negative
      correlation before birth and none after birth, this indicates that some preterm
      infants may be subject to greater drops in UVPO2 during delivery than term
      infants. The magnitude of the drop increases with additional complications and
      immaturity. However, not all preterms have normal UVPO2 values for gestational
      age antepartum. Some preterms already have a low UVPO2 in utero and experience a
      drop in UVPO2 during delivery as well.

PMID- 8880633
TI  - A comparison of the shake test, optical density, L/S ratio (planimetric and
      stechiometric) and PG for the assessment of fetal lung maturity.
AB  - Our aim was to determine the diagnostic accuracy and reliability of four tests
      for the assessment of fetal lung maturity (FLM): shake test, optical density at
      650 nm (OD650), lecithin to sphingomyelin ratio (L/S) by planimetry and
      stechiometry, and presence of phosphatydylglycerol. Amniotic fluid was obtained
      from 74 patients at various gestational ages. The shake test and the OD650 were
      performed according to published methods L/S was determined by TLC (thin-layer
      chromatography) and the ratio assessed by planimetry and stechiometrically by
      measurement of organic phosphorus from the chromatographic spots. PG was assessed
      similarly by TLC. When correlated with gestational age at amniocentesis, all
      tests correlated positively: shake test (r = 0.46, p < 0.005); OD650 (r = 0.31, p
      < 0.005); planimetric L/S (r = 0.77, p < 0.005); stechiometric L/S (r = 0.52, p <
      0.005) and PG (r = 0.54, p < 0.005). The diagnostic accuracy of each test was as
      follows: the shake test and the OD650 had a sensitivity of 50%, while the
      steciometric L/S had a sensitivity of 75%, the planimetric L/S and the presence
      of PG were 100%. All four tests demonstrated a specificity greater than 64%, the
      highest for the PG presence being (83%) and the shake test (86%). Predictive
      negative values for lung maturity were > 93% for all tests, with the highest for
      the planimetric L/S and presence of PG being (100%). The study confirms that the
      determination of L/S ratio is still superior to other tests in terms of overall
      diagnostic accuracy. In addition, it was found that presence of PG was highly
      associated with the absence of respiratory complications in the newborn.

PMID- 8880634
TI  - Beta-endorphin immunoreactivity levels in CSF after laryngeal chemoreflex
      activation correlate with apnoea duration in piglets.
AB  - The activation of the laryngeal chemoreflex may be a pathogenic mechanism in
      apnoea, apparent life threatening events, and SIDS. Infants with apnoea and
      increased levels of beta-endorphin immunoreactivity in CSF have been successfully
      treated with naloxone. Beta-endorphin may induce respiratory depression, and
      naloxone is a beta-endorphin antagonist. We therefore wanted to measure beta
      endorphin levels in CSF before and after the chemoreflex induced apnoea. This
      study includes 13 piglets, 5-10 days of age, treated with and without naloxone.
      Respiration, blood pressure, and heart rate were monitored. CSF was sampled
      before and after the laryngeal chemoreflex induced apnoea. We found a shorter
      duration of apnoea in the piglets which had received naloxone than in those which
      did not (p = 0.02). The beta-endorphin immunoreactivity levels in CSF increased
      after apnoea, and the increased levels correlated positively with the duration of
      the apnoea in the piglets which had not received naloxone (r = 0.94, p = 0.02),
      but not in those pretreated with naloxone (r = 0.1, p = 0.8). The median amount
      of beta-endorphin immunoreactivity in CSF after apnoea in the naloxone-treated
      piglets was not significantly different from that in the non-treated piglets: 615
      +/- 589 (n = 7) fmol/ml CSF and 984 +/- 851 (n = 6) fmol/ml CSF, respectively.
      The beta-endorphin immunoreactivity levels measured before the apnoea were less
      than 4.3 fmol/ml CSF. CONCLUSION: The laryngeal chemoreflex induced apnoea may
      possible be partly mediated by beta-endorphin.

PMID- 8880635
TI  - Inappropriate secretion of umbilical plasma catecholamines in preterm compared to
      term neonates.
AB  - To investigate the gestation and stimulus related catecholamine secretion and
      degradation at birth free and sulfoconjugated adrenaline, noradrenaline and
      dopamine were analysed in the umbilical artery and vein of 35 preterm and 75 term
      neonates. A highly sensitive radioenzymatic assay was used for the determination
      of free catecholamine levels, sulfoconjugated catecholamines were analysed after
      addition of 25 mU arylsulfatase type VI. Levels of free catecholamines were
      significantly lower in preterm as compared to term newborns. Hereby, adrenaline
      levels significantly correlated with the gestational age, birth weight, and birth
      length. Sulfoconjugated catecholamine levels were similarly lower, but only
      sulfoconjugated noradrenaline reached differences of statistical significance.
      The placental extraction rate of adrenaline and noradrenaline was significantly
      lower in preterm as compared to term neonates. Only in term but not in preterm
      neonates, arterial pH- and pCO2-levels significantly correlated with arterial
      plasma catecholamine levels. Therefore, lower catecholamine levels in preterm
      compared to term neonates result from lower secretion of catecholamines rather
      than increased degradation and may contribute to their frequent surfactant
      deficiency. In addition, the inadequate and diminished catecholamine secretion of
      preterm neonates may play a significant part in their postnatal adaptation
      problems like hypoglycaemia, hypothermia and occurrence of wet lungs.

PMID- 8880636
TI  - Immunmodulating cytokines induce term and preterm parturition.
AB  - The aim of our study was to investigate if cytokines, which are able to cause
      preterm delivery is case of intraamniotic infection, also participate in the
      mechanisms of normal term labor. Therefore we estimated cytokine concentrations
      in cercicovaginal secretions of 96 patients, divided into four different
      collectives. In collective A (women with spontaneous term labor) cytokine
      concentrations raised from a median level of 278 pg/ml for Il-1 beta and 263
      pg/ml for Il-6 in early term labor to a median level of 3351 pg/ml for Il-1 beta
      and 39,442 pg/ml for Il-6 at complete cervical dilatation. TNF-alpha-exclusively
      appeared after spontaneous rupture of fetal membranes. In collective B and C
      (women with preterm rupture of fetal membranes) cytokine concentrations declined
      from a maximum level of 1425 pg/ml for TNF-alpha, 12,982 pg/ml for Il-1 beta and
      29,727 pg/ml for Il-6 soon after preterm rupture of membranes to a minimum level
      of 93 pg/ml for TNF-alpha, 851 pg/ml for Il-1 beta and 780 pg/ml for Il-6 with
      remission of labor in case of successful tocolytic treatment. High concentrations
      reappeared with the onset of labor, unresponsive to tocolysis. In collective D
      (women with intact membranes) TNF-alpha was not detectable and Il-1 beta and II-6
      appeared exclusively in the presence of labor. Our results suggest, that normal
      term labor may be controlled by biochemical processes, similar to infection
      associated signal transduction, which is commonly accepted to induce preterm
      labor.

PMID- 8880637
TI  - Independent effect of maternal birth weight on infant birth weight.
AB  - The relationship between the birth weights of the mother and her infant was
      evaluated in a sample of 106 women consecutively delivered of a single live
      birth. Women were included in the study if their birth weight was available in
      hospital files or from another reliable source. Women that were themselves a twin
      or had diseases complicated the course of the pregnancy were excluded. A positive
      significant correlation was found between mother and infant birth weights (r =
      0.29, p = 0.003). This correlation remained significant (partial r = 0.22, p =
      0.039) after adjusting for other covariables such as the mother's age, height,
      education, whether the pregnancy was planned, number of cigarettes smoked daily
      during pregnancy, month of first antenatal visit and number of visits, weight at
      end-pregnancy, gestational age and sex of the newborn. In the multiple linear
      regression model, mother's birth weight explained 3% of the variation observed in
      infant birth-weight. A weaker crude correlation was also found between mothers'
      birth weight and gestational age (r = 0.19, p = 0.06). This study shows that
      maternal birth weight is an independent predictor of infant birth weight, and
      confirms previous findings suggesting that this maternal factor has a stronger
      effect on the birth weight than on the gestational age of the newborn.

PMID- 8880638
TI  - Advanced maternal age and smoking: risk factors for admission to a neonatal
      intensive care unit.
AB  - The aim of this study was to assess if advanced maternal age and cigarette
      smoking increased the requirement for admission to the neonatal intensive care
      unit (NICU) and if those factors acted synergistically. Retrospective analysis
      was made of 3518 singleton pregnancies receiving antenatal care and delivering at
      King's College Hospital from 1 January 1992 to 31 December 1992. The maternal age
      was greater than 35 years in 356 women (10.1% of the total) and 49 (13.8%) of
      those were cigarette smokers. There was an inverse relationship between maternal
      age and smoking. Two hundred and fifty-nine infants were admitted to the NICU.
      Logistic regression analysis revealed a significant relationship between maternal
      age and admission (p < 0.05), but no independent effect of maternal smoking. The
      proportion of infants from smoking mothers of advanced age (> 35 years) admitted
      to the NICU, however, was greater than that from young (< or = 35 years) smoking
      mothers (p < 0.05). Advanced maternal age does increase the requirement for NICU
      admission and this effect is enhanced by smoking.

PMID- 8880639
TI  - Neurodevelopmental outcome of infants exposed to indomethacin antenatally.
AB  - The use of indomethacin as a tocolytic agent has been limited because of
      potential fetal and neonatal complications. We investigated the neonatal and
      neurodevelopmental outcome of preterm infants exposed antenatally to this drug.
      The records of 779 women admitted in premature labor during a five year period
      were reviewed. Nineteen women who received indomethacin (initial dose of 50-100
      mg followed by 50-100 mg/day) and their 25 infants were identified. Delivery was
      delayed for a week or longer in 86.6% of the mothers. There were two deaths: a
      stillborn with multiple congenital anomalies and a neonate with congenital
      listeriosis. Seven infants were born at term without complications. Fifteen
      infants born prematurely were compared to 15 control infants not exposed to
      indomethacin antenatally. There were no statistically significant differences
      between the two groups in the prevalence or severity of thrombocytopenia,
      hyperbilirubinemia, intraventricular hemorrhages, patent ductus arteriosus,
      persistent pulmonary hypertension, bronchopulmonary dysplasia, and necrotizing
      enterocolitis. Mean BUN, creatine, and urine output for the first three days of
      life were similar in the two groups. No differences were found at the 6-12 month
      neurodevelopment assessment. We found no neonatal complications attributable to
      the antenatal use of indomethacin.

PMID- 8880640
TI  - Research accumulating on teenage alcohol abuse.

PMID- 8880641
TI  - Protection of privilege recognized.

PMID- 8880642
TI  - All in a day's work--exploring psychosocial rehabilitation ideas and programs in
      practice settings.

PMID- 8880643
TI  - Psychiatric rehabilitation: a breath of fresh air in a turbulent health-care
      environment.
AB  - 1. Some of the new factors influencing our practice are managed care, outcome
      measures, financial incentives, consumer empowerment, civil liberties, and the
      Americans with Disabilities Act (ADA). 2. We must step forward to grasp these new
      concepts and make them our own, to maintain our role as effective leaders in the
      area of community-based psychiatric-mental health care. 3. Incorporating
      principles of psychiatric rehabilitation into nursing practice creates
      opportunities to strengthen relationships and create partnerships among consumers
      of mental health services and their families, nurses, and other providers.

PMID- 8880644
TI  - National clearinghouse serves mental health consumer movement.

PMID- 8880645
TI  - A nurse battling with her own depression.

PMID- 8880646
TI  - My role as a consumer-provider: challenges and opportunities.

PMID- 8880647
TI  - My quest for inner peace.

PMID- 8880648
TI  - Overcoming schizophrenia. Interview by Shirley A. Smoyak.

PMID- 8880649
TI  - Blending two realities into a unique perspective. Interview by Shirley A. Smoyak.

PMID- 8880650
TI  - Prenatal predisposition and the clinical management of some pediatric conditions.
AB  - Theoretical understanding of psychosexual development, particularly in regard to
      sexual identity, has undergone several historical changes. Most notable has been
      the transition away from a learning paradigm, which held that individuals are
      psychosexually neutral at birth and that they develop their sexual identity due
      to rearing. This has shifted to contemporary acceptance that an interaction of
      both nature and nurture is responsible for psychosexual development. That there
      probably exists an inherent predisposition or bias toward a male or female
      identity, which is inferred by prenatal influences, is also current theory.
      However, while this shift has occurred in the theoretical understanding of the
      phenomenon, a comparable shift has not occurred in the clinical management of
      individuals where sex assignment or reassignment is a real issue. The theoretical
      change and real case management should be concordant.

PMID- 8880651
TI  - The sexual desire inventory: development, factor structure, and evidence of
      reliability.
AB  - The purpose of this investigation was to develop a self-administered
      questionnaire to measure sexual desire. In the development phase, items were
      generated and pilot-tested with 24 subjects. Based on these data, items were
      deleted, added, or modified. Next, in Study One, the Sexual Desire Inventory
      (SDI) was administered to 197 females and 117 males. Factor analyses revealed
      that the SDI was multifactorial; however, none of the generated factor solutions
      up to five factors yielded a good fit. Interpretation of the factors led to
      revisions of the SDI. It was hypothesized that sexual desire might consist of two
      related dimensions; dyadic sexual desire and solitary sexual desire. Items on the
      SDI were modified to measure these two dimensions, and the revised SDI was
      administered to 249 females and 131 males. Factor analysis supported the presence
      of these two dimensions. Internal consistency estimates using Cronbach's alpha
      revealed coefficients of .86 for dyadic sexual desire and .96 for solitary sexual
      desire, providing preliminary evidence for the reliability of the SDI. The
      implications of these findings are discussed.

PMID- 8880652
TI  - "Love" and the mental health professions: toward understanding adult love.
AB  - This essay explores three aspects of the normal processes of adult-adult love:
      falling in love, being in love, and staying in love. It describes the emotions,
      defenses, and challenges inherent in each phase. Love is an ordinary but
      immensely powerful adult aspiration. As a term it is impossible to define in any
      singular sense. The attainment of its lofty purposes requires profound
      intrapsychic adjustments involving creative acts of imagination, the integration
      of ideals with reality, evolving adaptations to the partner, the maintenance of a
      positive internal image of the partner, and ongoing struggles to overcome self
      interest. These adjustments have not been well characterized by the mental health
      professions. This is ironic since a large portion of our work involves caring for
      love's casualties--that is, people whose miseries relate to their inability to
      successfully negotiate the phases of love or whose happiness is limited by their
      partners who cannot. Six arguments for ending professional avoidance of the topic
      are offered, the most compelling of which are love's relevance to both the
      pathogenesis of mental suffering and to the art of psychotherapeutic healing.

PMID- 8880653
TI  - A brief survey of the current sexual practices of a population admitted for
      inpatient treatment of drug dependence.
AB  - We studied a population of high-risk drug users concerning their current sexual
      practices. They had a pattern of inconsistent or infrequent condom use. Only
      11.5% reported always using condoms; 38.2% reported never using them; and 50.3%
      reported using them sometimes. Experimental educational programs have
      demonstrated the feasibility of changing sexual behaviors in illicit drug users
      by using innovative techniques targeted specifically at them. The application of
      sex and marital therapy techniques to changing high-risk behaviors is not widely
      discussed in the substance abuse literature. The hypothesis that the application
      of the techniques of sex and marital therapy in educational programs for drug
      users will improve outcomes of HIV prevention should be tested.

PMID- 8880654
TI  - Sexual side effects of antidepressants: a review.
AB  - Antidepressant-induced adverse sexual effects are becoming more frequently
      reported by patients who require pharmacotherapy. A MED-LINE search was conducted
      to generate articles reporting such events. We report here on the sexual side
      effects associated with tricyclics, monoamine oxidase inhibitors including
      moclobemide, selective serotonin reuptake inhibitors, bupropion, and on the newer
      antidepressants venlafaxine and nefazadone. We conclude that adverse sexual
      effects are an increasingly important side effect of antidepressant medications,
      and patients must be routinely asked about their occurrence.

PMID- 8880655
TI  - Treatment of antidepressant-induced sexual side effects.
AB  - Sexual side effects of antidepressant medications are becoming more frequently
      encountered by patients who require pharmacotherapy. A MEDLINE search was
      conducted to generate articles that address methods of treating these
      iatrogenically induced clinical situations. We report here on treatment
      strategies to alleviate these adverse events. We conclude that clinicians should
      routinely ask about sexual side effects due to antidepressants and that they
      should be treated promptly to ensure patient compliance with antidepressant
      pharmacotherapy.

PMID- 8880656
TI  - Low-dose imipramine for thioridazine-induced male orgasmic disorder.
AB  - Male orgasmic disorder is commonly encountered among patients treated with
      thioridazine. This side effect interferes significantly with sexual satisfaction.
      In this pilot study, eight male schizophrenic patients who complained of orgasmic
      disorder, compatible with probable retrograde ejaculation during thioridazine
      treatment, were given concomitant low-dose imipramine (25-50 mg at bedtime). Four
      of the eight reported complete resumption of their previous ejaculatory function,
      and in one patient there was a partial, but substantial, improvement. Three
      patients noted no change. It appears that imipramine might be beneficial for some
      patients with thioridazine-induced male orgasmic disorder.

PMID- 8880657
TI  - Cost-benefit and cost-effectiveness analyses of behavioral marital therapy as an
      addition to outpatient alcoholism treatment.
AB  - Thirty-six newly abstinent married male alcoholics, who had recently begun
      outpatient individual alcoholism counseling, were randomly assigned to a no
      marital-therapy control group or to 10 weekly sessions of a behavioral marital
      therapy (BMT) or an interactional couples group. The cost-benefit analysis of BMT
      plus individual alcoholism counseling showed (a) decreases in health care and
      legal costs in the 2 years after as compared to the year before treatment, (b) a
      positive cost offset, and (c) a benefit-to-cost ratio greater than 1 indicating
      that health and legal system cost savings (i.e., benefits) exceeded the cost of
      delivering the BMT treatment. None of the positive cost-benefit results observed
      for BMT were true for participants given interactional couples therapy plus
      individual alcoholism counseling for which posttreatment utilization costs
      increased. Thus, adding BMT to individual alcoholism counseling produced a
      positive cost benefit, whereas the addition of interactional couples therapy did
      not. Individual counseling both alone and with BMT added showed substantial and
      significant cost savings from reduced utilization that substantially and
      significantly exceeded the cost of delivering the treatment; and the two
      treatments did not differ significantly on these cost savings and cost offsets.
      Individual counseling alone did have a significantly more positive benefit-to
      cost ratio than BMT plus individual counseling due to the lower cost of
      delivering the individual counseling which was about half the cost of delivering
      BMT plus individual counseling. Cost-effectiveness analyses indicated that BMT
      plus individual counseling was less cost effective than individual counseling
      alone and modestly more cost effective than interactional therapy in producing
      abstinence from drinking. When marital adjustment outcomes were considered, the
      three treatments were equally cost effective except during the active treatment
      phase when BMT was more cost effective than interactional couples therapy. Study
      limitations are discussed.

PMID- 8880658
TI  - Late-life problem drinking: personal and environmental risk factors for 4-year
      functioning outcomes and treatment seeking.
AB  - Recent research emphasizes the importance of identifying older problem drinkers.
      However, very little is known about the longitudinal course and predictors of
      late-life problem drinking. This prospective study of late-life problem drinkers
      (N = 581) focused on predictors of alcohol consumption, drinking problems,
      depression, and treatment seeking over a 4-year interval. Heavier baseline
      alcohol use and being male independently predicted more alcohol consumption 4
      years later; more baseline drinking problems and early-onset status independently
      predicted more drinking problems at follow-up. Independent of other factors, more
      initial depressive symptoms and chronic health stressors portended more
      depressive symptoms at follow-up. Individuals who initially sought more
      treatment, and who had more chronic health and spouse stressors at baseline, were
      more likely to seek help 4 years later. Heavier reliance on avoidance coping
      strategies heightened the risk that stressors and friends' approval of drinking
      would lead to more drinking problems at follow-up. However, for individuals who
      had more drinking problems at baseline, such environmental risk factors as
      negative health events and friend stressors predicted fewer subsequent drinking
      problems.

PMID- 8880659
TI  - A Cocaine Negative Consequences Checklist: development and validation.
AB  - Awareness of negative consequences of cocaine use is theoretically important for
      motivation for treatment and relapse prevention. This study reports on the
      development of an instrument designed to assess cocaine users' self-reported
      negative consequences of cocaine use. Two samples of cocaine users in treatment
      for substance abuse completed the Cocaine Negative Consequences Checklist (CNCC).
      The measure, which is unidimensional in nature with four content area subscales
      that may be scored, was found to possess excellent reliability across the two
      samples. The convergent and discriminant validity of the CNCC was supported by
      the pattern of relationships with other measures of cocaine consequences, cocaine
      use, the Addiction Severity Index, and with demographic measures. Further
      research is needed on the utility of this measure in treatment and research.

PMID- 8880660
TI  - Prevalence and correlates of drug use and DSM-IV drug dependence in the United
      States: results of the National Longitudinal Alcohol Epidemiologic Survey.
AB  - This study presents updated estimates of the prevalence and examines the
      correlates of drug use and dependence in a representative sample of the U.S.
      population. The prevalence of lifetime drug use was 15.6%, with 4.9% of the
      respondents reporting drug use during the past 12 months. Lifetime and 12-month
      prevalence of drug dependence were estimated at 2.9% and 0.8%, respectively. Men
      were significantly more likely to use drugs than women, and drug use and
      dependence were much more common among cohorts born after World War II. The data
      indicated that rates of dependence among women were quickly approaching the rates
      among men in the younger cohorts. Members of the youngest cohort, between the
      ages of 18 and 24 years at the time of the interview, were more likely to use
      drugs, to become dependent, and to persist in dependence compared to the older
      cohorts, including Cohort 2 who experienced adolescence at the height of
      widespread introduction of illicit drugs among youth in the mid-1960s. The
      demographic correlates of first use, onset of dependence, and persistence of
      dependence varied as a function of the stage of progression. Implications of
      these findings are discussed in terms of changes over time in drugs of choice and
      dependence liability and vulnerability among recent drug users.

PMID- 8880661
TI  - Gender differences in the probability of alcohol treatment.
AB  - Interview data from 7,359 adults 18 years of age and over who met the DSM-IV
      criteria for alcohol abuse or dependence at some point during their lives
      revealed that 23.0% of the men and 15.1% of the women ever received treatment for
      alcohol problems. The median interval from onset of disorder to first treatment
      was between 2 and 3 years longer for men than women. This difference did not
      result from women being more likely than men to initiate treatment shortly after
      onset of an alcohol use disorder, but rather from men being more likely than
      women to initiate treatment in the period well after onset. Excluding treatment
      initiated prior to the clinical onset of the disorders or after cessation of
      drinking, men's and women's cumulative conditional probabilities of having
      initiated treatment by 30 years after onset of alcohol abuse or dependence were
      .424 and .356, respectively. Within the first 8 years after onset of abuse or
      dependence, men's and women's probabilities of initiating treatment were about
      the same, but men were 13% to 20% more likely to initiate treatment in the period
      from 8 to 25 years after onset. Use of proportional hazards models to adjust for
      factors including sociodemographic characteristics, prior consumption, severity
      of disorder, and comorbid drug use and depression revealed that men's and women's
      likelihoods of ever having received treatment did not differ for the most
      severely affected, those with 20 or more symptoms of abuse or dependence. Among
      those less severely affected, the male-to-female ratio in the likelihood of
      treatment declined with severity from 1.75 (1 symptom) to 1.24 (15 symptoms).

PMID- 8880662
TI  - Gender roles and interactions in drinking and drug use.
AB  - In gender-focused discussions of alcohol and other drug use and problems, the
      emphasis has usually been on the individual male or female or on the genders as
      aggregates of individuals. But most drinking and much drug use have strong social
      and interactional elements, where gender roles and often gendered interactions
      come into play. Drawing on the existing literature, opportunities for research on
      gender roles and interactions in drinking and drug use and problems are discussed
      under the following headings: courtship and affectional preference; sexuality;
      marriage and partnership; parenthood; friendship and peer relations; work roles;
      informal social control (spouse, relatives, friends); and domination, violence,
      and abuse.

PMID- 8880663
TI  - Latent variable models of alcohol-related constructs.
AB  - This study examines the improvement in validity coefficients and structural
      relationships derived from formally modeling latent variables of adverse alcohol
      related constructs. Results of a confirmatory factor analysis of responses from
      8,755 participants in the 1988 National Household Survey of Drug Abuse support a
      three-factor model of alcohol abuse, dependence, and adverse consequences. A
      comparison of construct intercorrelations shows latent variables to be superior
      to measurement approaches using unweighted sums, quantity x frequency
      calculation, and single-item measurement.

PMID- 8880664
TI  - The use of alcohol home delivery services by male problem drinkers: a preliminary
      report.
AB  - Alcohol home delivery services (AHDS) provide convenient and confidential access
      to alcohol, yet little is known about their use. The purpose of this report is to
      present preliminary data describing the use of AHDS by problem drinkers. We
      surveyed 174 males regarding social and demographic characteristics, alcohol use
      history, and use of AHDS. Use of AHDS was most common among problem drinkers.
      When statistically controlling for the effects of demographic and social
      characteristics, regular drinkers without a history of alcohol problems were
      significantly less likely to have had alcohol delivered than problem drinkers, p
      = .0036. Contrary to expectation, medically ill alcoholics with advanced and
      disabling medical complications of heavy drinking were not more likely than other
      problem drinkers to have alcohol delivered. Living in an urban area and not
      having a vehicle available were associated with the use of AHDS. The public
      health and safety considerations of alcohol availability via home delivery are
      discussed.

PMID- 8880665
TI  - Does HIV test result influence methadone maintenance treatment retention?
AB  - We compared groups of opioid users new to methadone maintenance to determine if
      persons who first learn that they are HIV-seropositive in a drug treatment
      program are more likely to drop out of treatment than persons who learn they are
      seronegative. We found no difference in patients' continuation in methadone
      treatment at either 6 or 12 weeks associated with HIV serostatus. Our findings
      suggest that voluntary HIV testing can be implemented as part of AIDS prevention
      programs with little fear of adversely affecting treatment outcomes.

PMID- 8880666
TI  - Enhancing substance abuse treatment with case management. Its impact on
      employment.
AB  - This article examines the effectiveness of strengths-based case management in
      assisting persons with substance abuse problems improve employment-related
      functioning. In a study of 632 veterans seeking treatment for substance abuse
      problems, Wright State University's Enhanced Treatment Project found that
      veterans in substance abuse treatment had improved in several areas of employment
      functioning, including number of days employed. Among clients who expressed
      interest in receiving assistance with employment-related issues, those who
      received strengths-based case management demonstrated additional improvement in
      employment functioning including more days employed, fewer employment problems
      and being less troubled about their employment situation. Correlations between
      improved employment functioning and improved functioning in other life areas
      further support the value of case management. The implications of these findings
      for the inclusion of case management services in substance abuse treatment
      programs will be discussed.

PMID- 8880667
TI  - The dream interview method in addiction recovery. A treatment guide.
AB  - The Dream Interview Method is a recently developed tool for dream interpretation
      that can facilitate work on addiction issues at all stages of recovery. This
      paper describes the method in detail and discusses examples of its application in
      a group composed of individuals in varying stages of the recovery process. It
      permits the therapist to accelerate the development of insight, and once the
      method is learned, it can be applied in self-help formats.

PMID- 8880668
TI  - Can psychiatric and chemical dependency treatment units be smoke free?
AB  - The feasibility and appropriateness of establishing smoke-free psychiatric and
      chemical dependency treatment units are topics of recent interest. This paper
      reviews the literature on the implementation of smoke-free policies in
      psychiatric and chemical dependency treatment units. Several issues are addressed
      including (a) the concerns raised by treatment staff regarding the implementation
      of a smoke-free policy, (b) the effects of involuntary smoking cessation or
      reduction on the treatment and/or recovery of patients, (c) the utilization of
      smoking cessation interventions by patients and staff, and (d) the effects of a
      smoke-free environment on the smoking behavior of patients and staff. It is
      concluded that a smoke-free environment is a reasonable and achievable goal in
      these settings. However, the implementation of a smoke-free policy in chemical
      dependency treatment units has met with several more problems than those observed
      in psychiatric settings. Recommendations for further clinical research and
      program implementation are offered.

PMID- 8880669
TI  - Counseling Latino alcohol and other substance users/abusers. Cultural
      considerations for counselors.
AB  - This article presents a sociocultural alcohol/drug counseling model for
      counselors working with Latino users/abusers. Intended to supplement different
      treatment models, this model addresses pre-treatment issues of Latino
      users/abusers. A demographic overview of Latinos and a discussion of selected
      Latino cultural values and issues as they relate to substance use/abuse are
      included. These cultural values include Simpatia, Personalismo, Familismo, Gender
      Roles (Machismo and Hembrismo/Marianisimo), Verguenza, and Espiritismo. Along
      with identifying misperceptions and issues that may occur within the counseling
      session, specific recommendations and interventions for counselors are provided.

PMID- 8880670
TI  - Personality assessment of substance-dependent patients in a therapeutic
      community.
AB  - The design and implementation of a personality assessment system for severely
      substance-dependent men in a therapeutic community (TC) are described. The system
      was designed from a treatment utility perspective (Hayes, Nelson, & Jarrett,
      1987) and uses the Personality Research Form E (Jackson, 1984) to provide each
      patient with feedback (a) describing his normal personality traits, (b)
      predicting his probable pattern of adjustment to the treatment setting, and (c)
      prescribing specific actions he can take to address potentially problematic
      behaviors. Discussing the the results with the patient helps him cope with the
      TC. Reviewing the assessment results with the staff promotes their empathy for
      the patient as a person whose behavior can be understood as an interaction of his
      personality with the specific demands of the TC rather than seeing the patient in
      exclusively pathological terms. Specific suggestions for behavior change guide
      both the patient and the staff and are potentially useful in various treatment
      settings.

PMID- 8880671
TI  - Shelter-based treatment of the homeless alcoholic.
AB  - We describe a model for integrating municipal shelter and hospital-based
      alcoholism outpatient treatment services for the homeless alcoholic, and report
      on its outcome at 12 months. The experimental program was designed to increase
      homeless patient's length of stay in treatment and was based on integrating
      clinic services for homeless men at Bellevue Hospital in New York with an
      abstinence oriented dormitory, the "Clean and Sober" Unit in a municipal shelter.
      The study sample consists of 189 consecutive male admissions to an intensive
      outpatient alcoholism treatment program in the Bellevue hospital. The patients'
      outcome was assessed in relation to their place of residence divided in three
      groups: the experimental group counts 100 men housed in the Clean and Sober Unit.
      The two contrast groups counted 34 residents of various unaffiliated shelters and
      55 domiciled men with independent living arrangements. The three subject groups
      did not differ significantly on demographic or clinical characteristics. After 12
      months, residents in unaffiliated shelters were significantly less likely to be
      retained than the domiciled patients and showed a trend towards less retention
      than the experimental group.

PMID- 8880672
TI  - The efficacy of substance abuse education among dual-diagnosis patients.
AB  - The purpose of this study was to determine whether patient education programs
      were effective at improving knowledge of substance abuse among dual-diagnosis
      patients. Adult patients at a general psychiatry hospital were identified for a
      history of substance abuse. Of the 51 patients included in the study, 25 were on
      forensic units, 7 were in a private ward, and 19 were on the public unit.
      Patients were given a pretest at the beginning of the study and received an
      identical posttest prior to discharge or at the end of the study. The patients on
      the public unit received up to 16 h per week of Alcoholics Anonymous meetings,
      alcohol/drug education meetings, group therapy, and other forms of intervention.
      These patients demonstrated statistically significant improvements between
      pretest and posttest scores, while those on the forensic units who received only
      2 h of intervention per week did not show improvements in substance abuse
      knowledge. These and other findings have been used to improve education programs
      for our dual-diagnosis patients across the institute.

PMID- 8880673
TI  - Quality of treatment data. Reliability over time of self-reports given by clients
      in treatment for substance abuse.
AB  - This study examines the reliability over a 2-month period of self-reports of drug
      use, sexual behaviors, and use of treatment services provided by 2,968 clients
      participating in a large, multisite, prospective study of drug treatment in the
      United States-the Drug Abuse Treatment Outcome Study (DATOS). Analyses focus on
      responses to 62 pairs of logically related questions that were asked at two
      points in time: (1) 1 month after entry into treatment, and (2) 3 months after
      entry into treatment. Subjects' responses to questions asked at these two time
      points are assessed for logical consistency. Prior analyses of self-reports
      provided by DATOS clients at one point in time (entry into treatment) found
      surprisingly high levels of within-interview consistency in their reporting of
      alcohol use (Turner & Hubbard, 1995) and cocaine use (Adair, Craddock, Miller, &
      Turner, 1995). The crosstemporal tests of consistency reported in this article
      eliminate several potential sources of artifactual consistency that may have
      affected prior analyses, (e.g., consistency imposed by an interviewer or
      constructed by a respondent during the course of a single interview). Contrary to
      expectations, crosstemporal comparisons reveal high levels of logical consistency
      in clients' responses. The mean percent of substantively inconsistent responses
      ranges from 0.7% for questions asking about frequency of drug use to 4.4% for
      questions asking about sexual behaviors.

PMID- 8880674
TI  - An existential model for promoting life change. Confronting the disease concept.
AB  - This paper outlines an existentially based psychoeducational model for dealing
      with substance abuse clients' questions concerning the possibility of successful
      behavior change. Clients frequently misinterpret the "disease model" as meaning
      that they are powerless victims of addiction. Clients' readiness to change can be
      enhanced by providing them with a coherent method of conceptualizing the task of
      rehabilitation, one that explains how change is possible in spite of the "disease
      model" of addiction, rather than the confusing mix of self-help, "bootstrap"
      philosophy and "disease" talk presented in many rehabilitation programs.
      Productive methods of dealing with clients' guilt are presented, along with the
      need to develop a positive purpose in life as an essential aspect of effective
      relapse management.

PMID- 8880675
TI  - Alcoholic patients' decisions about halfway houses. What they say, what they do.
AB  - Because of the important role of halfway houses in the recovery of many alcoholic
      patients, patients' attitudes toward accepting placement in a halfway house were
      studied in a state hospital's alcohol rehabilitation program. Verbal intentions
      to accept or not to accept placement were measured at the beginning and again
      toward the end of the program sequence. Both assessments showed a strong
      correlation with the patients' actual behaviors. The relationships between
      intentions and ultimate choices were moderated both by the amount of time between
      observations and, independently of the passage of time, by the subjects'
      experience with or knowledge about halfway houses. Changes over the course of the
      program were mostly positive (favorable toward going and actually doing so).
      These shifts mainly involved the people who had been initially undecided about
      placement in a halfway house. Amount of time spent in the rehabilitation program
      was unrelated to patients' initial intentions toward going and had little bearing
      on their final decisions.

PMID- 8880676
TI  - Is auricular acupuncture beneficial in the inpatient treatment of substance
      abusing patients? A pilot study.
AB  - Patients with comorbid substance abuse problems who were admitted to a
      psychiatric unit of a general hospital over an 11-month period were offered
      treatment with auricular acupuncture. Subsequently and retrospectively, the
      medical records of these patients were examined to assess compliance, side
      effects, impact on course, and acceptance of discharge recommendations. Patient's
      continuation of treatment in destination programs was also followed. Seventy
      seven patients were offered acupuncture: 30 patients refused or had four or fewer
      treatments (control group), and 47 had acupuncture five or more times (treatment
      group). The treatment group did significantly better than the control group as
      indicated by the following findings: compliance with psychiatric/substance abuse
      treatment on the unit was 75% in the treatment group vs. 20% in the control
      group, noncompliance or AMA discharge rate was 2% in the treatment group vs. 40%
      in the control group, acceptance of staff's discharge recommendations was 77% in
      the treatment group vs. 37% in the control group, and 58% of the treatment group
      patients remained in follow-up treatment for at least 4 months, vs. only 26% of
      the control group patients. Average inpatient length of stay was 22 days for the
      treatment group patients compared to 16 days for the control group patients. Side
      effects in the treated patients were negligible. Auricular acupuncture thus
      appears to be a safe and inexpensive treatment modality that is easily
      administered and produces significant results. Its wider application in substance
      abuse treatment appears warranted.

PMID- 8880677
TI  - Java and its future in biomedical computing.
AB  - Java, a new object-oriented computing language related to C++, is receiving
      considerable attention due to its use in creating network-sharable, platform
      independent software modules (known as "applets") that can be used with the World
      Wide Web. The Web has rapidly become the most commonly used information-retrieval
      tool associated with the global computer network known as the Internet, and Java
      has the potential to further accelerate the Web's application to medical
      problems. Java's potentially wide acceptance due to its Web association and its
      own technical merits also suggests that it may become a popular language for non
      Web-based, object-oriented computing.

PMID- 8880678
TI  - The Vanderbilt University fast track to IAIMS: transition from planning to
      implementation.
AB  - Vanderbilt University Medical Center is implementing an Integrated Advanced
      Information Management System (IAIMS) using a fast-track approach. The elapsed
      time between start-up and completion of implementation will be 7.5 years. The
      Start-Up and Planning phases of the project are complete. The Implementation
      phase asks one question: How does an organization create an environment that
      redirects and coordinates a variety of individual activities so that they come
      together to provide an IAIMS? Four answers to this question are being tested.
      First, design resources to be "scalable"--i.e., capable of supporting enterprise
      wide use. Second, provide information technology planning activities as ongoing
      core functions that direct local efforts. Third, design core infrastructure
      resources to be both reusable and expandable at the local level. Fourth, use
      milestones to measure progress toward selected endpoints to permit early
      refinement of plans and strategies.

PMID- 8880679
TI  - Remote analysis of physiological data from neurosurgical ICU patients.
AB  - Recent technical advances in Internet-based client/server applications and new
      multimedia communications protocols are enabling the development of cost
      effective, platform-independent solutions to the problem of remote access to
      continuously acquired physiological data. The UCLA Neurosurgery Intensive Care
      Unit (ICU) has developed a distributed computer system that provides access over
      the World Wide Web (WWW) to current and previously acquired physiological data,
      such as intracranial pressure, cerebral perfusion pressure, and heart rate from
      critical care patients. Physicians and clinical researchers can access these data
      through personal computers from their offices, from their homes, or even while on
      the road. The system creates and continuously updates a database of all monitored
      parameters in data formats that can readily be used for further clinical studies.
      This paper describes an extension to this system that allows for remote
      interaction with and analysis of the data via the WWW. Physicians can now pose a
      limited, predefined set of clinically relevant questions to the system without
      having to be at the patient's bedside.

PMID- 8880680
TI  - Generic data modeling for clinical repositories.
AB  - OBJECTIVE: To construct a large-scale clinical repository that accurately
      captures a detailed understanding of the data vital to the process of health care
      and that provides highly efficient access to patient information for the users of
      a clinical information system. DESIGN: Conventional approaches to data modeling
      encourage the development of a highly specific data schema in order to capture as
      much information as possible about a given domain. In contrast, current database
      technology functions most effectively for clinical databases when a generic data
      schema is used. The technique of "generic data modeling" is presented as a method
      of reconciling these opposing views of clinical data, using formal operations to
      transform a detailed schema into a generic one. RESULTS: A complex schema
      consisting of hundreds of entities and representing a rich set of constraints
      about the patient care domain is transformed into a generic schema consisting of
      roughly two dozen tables. The resulting database design is efficient for patient
      oriented queries and is highly flexible in adapting to the changing information
      needs of a health care institution, particularly changes involving the collection
      of new data elements. CONCLUSION: Conventional approaches to data modeling can be
      used to develop rich, complex models of clinical data that are useful for
      understanding and managing the process of patient care. Generic data modeling
      techniques can successfully transform a detailed design into an efficient generic
      design that is flexible enough to meet the needs of an operational clinical
      information system.

PMID- 8880681
TI  - A randomized controlled trial of a computer-based physician workstation in an
      outpatient setting: implementation barriers to outcome evaluation.
AB  - OBJECTIVE: A research prototype Physician Workstation (PWS) incorporating a
      graphical user interface and a drug ordering module was compared with the
      existing hospital information system in an academic Veterans Administration
      General Medical Clinic. Physicians in the intervention group received
      recommendations for drug substitutions to reduce costs and were alerted to
      potential drug interactions. The objective was to evaluate the effect of the PWS
      on user satisfaction, on health-related outcomes, and on costs. DESIGN: A one
      year, two-period, randomized controlled trial with 37 subjects. MEASUREMENTS:
      Differences in the reliance on noncomputer sources of information, in user
      satisfaction, in the cost of prescribed medications, and in the rate of
      clinically relevant drug interactions were assessed. RESULTS: The study subjects
      logged onto the workstation an average of 6.53 times per provider and used it to
      generate 2.8% of prescriptions during the intervention period. On a five-point
      scale (5 = very satisfied, 1 = very dissatisfied), user satisfaction declined in
      the PWS group (3.44 to 2.98 p = 0.008), and increased in the control group (3.23
      to 3.72, p < 0.0001). CONCLUSION: The intervention physicians did not use the PWS
      frequently enough to influence information-seeking behavior, health outcomes, or
      cost. The study design did not determine whether the poor usage resulted from
      satisfaction with the control system, problems using the PWS intervention, or the
      functions provided by the PWS intervention. Evaluative studies should include
      provisions to improve the chance of successful implementation as well as to yield
      maximum information if a negative study occurs.

PMID- 8880682
TI  - Lessons from evaluating an automated patient severity index.
AB  - OBJECTIVE: To report lessons learned from evaluation of an automated interface
      between a hospital clinical information system and a severity of illness index.
      DESIGN: A system was developed to convert coded electronic patient findings from
      the HELP System at LDS Hospital into the attributes used by the Computerized
      Severity Index (CSI) to calculate a severity of illness score. Performance was
      assessed by comparing the automated CSI score with the manual CSI score (from
      paper chart review) and by evaluating changes introduced by augmenting the manual
      CSI score with verified patient data discovered by the automated CSI method.
      MEASUREMENTS: The strengths and weaknesses of each method are presented. RESULTS:
      The automated CSI score matched the manual CSI score in 61% of the cases. Sources
      of errors were analyzed. When the automated score was in error, two-thirds of the
      time it was due to the lack of codes in the HELP system representing CSI
      concepts; one-third of the time it was due to nurses not using established HELP
      system codes. Surprisingly, significant problems were also discovered in the
      manual system, making it difficult to define a "gold standard". CONCLUSIONS:
      Automated computerized severity indices have great potential for future
      applicability once their performance exceeds that of the time-consuming manual
      chart review method. Neither automated nor manual methods are adequate at the
      present time. This area remains a fertile ground for future research.

PMID- 8880683
TI  - Testing informatics innovations: the value of negative trials.

PMID- 8880684
TI  - A new nitric oxide donor, NOC-18, exhibits a nociceptive effect in the rat
      formalin model.
AB  - The utility of a new nitric oxide (NO) donor, NOC-18, and the contribution of the
      neurotransmitter NO to nociception in response to tissue injury in rats, were
      examined following the subcutaneous injection of formalin into the hindpaw. This
      model induces biphasic responses in pain-related behavior, such that C-fiber
      activation during the first phase triggers a state of central sensitization
      characterized by the second phase. Formalin-induced nociceptive behavior was
      facilitated by intracerebroventricular administration of NOC-18 in the second
      phase, but not the first phase. This enhancement was completely abolished by the
      soluble guanylate cyclase inhibitor, methylene blue. These findings indicate that
      NO causes nociception via the NO-cGMP pathway in the central nervous system and
      NOC-18 proved to be a convenient and useful tool for the investigation of
      nociception-related NO.

PMID- 8880685
TI  - Effects of seven days of galactose feeding and aldose reductase inhibition on
      mast cells and vessel morphometry in rat sciatic nerve.
AB  - The association between mast cells and vessel morphometry in sciatic nerve was
      examined after seven days in animals fed a diet of 40% D-galactose and compared
      to control rats and to galactose-fed animals treated with the aldose reductase
      inhibitor, Tolrestat. Electron microscopy revealed an increase in the total
      number of mast cells and the number of degranulated mast cells in galactose-fed
      animals (7.8 +/- 2.9; 2.6 +/- 2.9; mean +/- SD) compared to controls (4.6 +/-
      2.1; degranulated mast cells were not seen in any control nerves) and Tolrestat
      treated, galactose-fed animals (4.4 +/- 2.5; 0.1 +/- 0.4). Although no
      significant differences were noted in the numbers of vessels between the three
      groups, an index of vasoconstriction was significantly increased in the galactose
      fed animals (0.115 +/- 0.048; mean +/- SD) compared to controls (0.068 +/- 0.011)
      and Tolrestat-treated, galactose-fed animals (0.075 +/- 0.20). These data suggest
      that mast cell degranulation is associated with the vascular constriction induced
      by seven days of galactose intoxication and that both may be prevented by
      inhibiting aldose reductase.

PMID- 8880686
TI  - An in vivo and in vitro H-magnetic resonance spectroscopy study of mdx mouse
      brain: abnormal development or neural necrosis?
AB  - Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily
      affecting young boys, often causing mental retardation in addition to the well
      known progressive muscular weakness. Normal dystrophin expression is lacking in
      skeletal muscle and the central nervous system (CNS) of both DMD children and the
      mdx mouse model. The underlying biochemical lesion causing mental impairment in
      DMD is unknown. 1H-magnetic resonance spectroscopy (1H-MRS) detects choline
      containing compounds, creatine and N-acetyl aspartate (NAA) in vivo. NAA is
      commonly used as a chemical marker for neurons, and a decline in NAA is thought
      to correlate with neuronal loss. Control mice were compared to mdx using a
      combination of in vivo and in vitro 1H-MRS methods to determine whether neural
      necrosis or developmental abnormalities occur in dystrophic brain. NAA levels
      were normal in mdx brain compared to controls suggesting minor, if any, neuronal
      necrosis in dystrophic brain. In contrast, choline compounds and myo-inositol
      levels were increased, indicative of gliosis or developmental abnormalities in
      dystrophic brain.

PMID- 8880687
TI  - Disappearance of 125I-labelled myelin basic protein from blood circulation and
      its degradation and accumulation in various tissues in rats.
AB  - Following acute central nervous system myelin injury, immunoreactive myelin basic
      protein (MBP) has been detected in the cerebrospinal fluid, blood and urine. In
      order to clarify the fate of MBP in the circulation, distribution and degradation
      of intravenously injected bovine MBP was followed in anaestethized rats for 5 to
      240 min by using 125I-labelled MBP. Five minutes after injection of a dose of 60
      400 ng of MBP, 44% of the label was recovered in the liver, 6.3% in the kidneys,
      4.7% in the lungs and 15% in the blood circulation, the corresponding figures at
      a dose of 0.8 mg being 51, 7.4, 0.8 and 22%. The liver discarded the label
      fastest, 3% of the dose remaining 4 h after injection. The amount of label in
      urine increased simultaneously, the recovery at 4 h being 5.5% of the lower and
      4.2% of the higher MBP dose. The percentage of total dose of the label per gram
      of tissue at 5 min (= distribution percentage, DP-5) was 3-4% in the liver and
      kidney and 1.6% in the spleen. The label content in the pancreas was increased at
      15-60 min, compared to the DP-5 of 0.3% with a two-fold maximum at 30 min. The
      duodenum concentrated MBP in a similar manner as the pancreas but not as
      extensively. The DP-5 of 0.1% in the thymus was concentrated two-fold with a
      maximum at 60 min. A slight concentration occurred in the heart. The DP-5 of
      0.03% in muscle, testis and brain was concentrated 3-fold at 60 min, 3.6-fold at
      60-240 min and 2-fold at 30-60 min in the aforementioned tissues, respectively.
      In spite of degradation of the label in tissues, the distribution of high
      molecular weight (HMW = TCA-precipitable) MBP was similar. Other experiments
      showed that the kidney, lung and duodenum contained most of the HMW MBP at 20 h.
      Upon continuous release of MBP, the pancrease, thymus, duodenum, muscle and
      testis would thus cumulatively concentrate MBP, and the kidney, lung and duodenum
      would be quantitatively most affected. MBP was previously shown to enter into
      cells of pancreative islets and to stimulate insulin and glucagon release. It
      could have biological effects in other tissues as well. These effects could
      explain some peripheral symptoms present in neurological disorders.

PMID- 8880688
TI  - The GTP-cyclohydrolase I gene in atypical parkinsonian patients: a clinico
      genetic study.
AB  - GTP cyclohydrolase I (GTPCH) has recently been identified as the first causative
      gene for Dopa-responsive dystonia (DRD). DRD typically presents with dystonia in
      the lower limbs in childhood, but may produce an akinetic-rigid syndrome in
      middle and old age. We have sequenced the GTPCH gene in 29 Parkinsonian patients
      without a positive family history for DRD, but who shared at least one feature of
      the akinetic-rigid presentation of DRD: 23 patients had at least one living
      relative who also suffered from an akinetic-rigid syndrome; 2 patients had an
      abnormally mild course of their parkinsonism which was extremely dopa-responsive.
      DNA was also analysed from 4 brain samples of patients who were clinically
      diagnosed as suffering from Parkinson's disease, but then did not show any
      pathological findings at post mortem. No changes in the sequence of the GTPCH
      gene were detected. We conclude that so far there is no evidence that mutations
      of the GTPCH gene are responsible for the development of parkinsonism in patients
      without a positive family history of DRD.

PMID- 8880689
TI  - Activity of alpha 1-antitrypsin and cigarette smoking in subarachnoid haemorrhage
      from ruptured aneurysm.
AB  - An altered equilibrium of protease/protease-inhibitor factors may be involved in
      the pathogenesis of aneurysm rupture: alpha 1-antitrypsin (alpha 1-AT) represents
      the most relevant inhibitor of elastase, a proteolytic enzyme enhancing catabolic
      processes of collagen metabolism. Cigarette smoking has been shown to
      significantly reduce the inhibitory effect of alpha 1-AT on proteases. In the
      present study we test the hypothesis whether the activity of alpha 1-AT is
      altered in patients with subarachnoid haemorrhage (SAH) and if is there any
      relationship between alpha 1-AT activity and the high risk of aneurysm rupture in
      smokers. The patients were subdivided in the following groups: (a) patients with
      unruptured aneurysm (n = 10); (b) patients presenting with SAH admitted within 48
      h after the episode (n = 20); (c) patients presenting with SAH admitted > 48 h
      after the episode (n = 14); (d) controls (n = 10): patients with neither
      cerebrovascular nor acute disease. Blood samples were obtained immediately at
      admission. Measurement of alpha 1-AT level was determined by immunoturbidimetric
      method. In order to obtain qualitative data about the anti-protease activity of
      alpha 1-AT (expressed as collagenase inhibitory percentage capacity (CIC) at
      different doses) we consider the 20 cases admitted for SAH within 48 h. The mean
      serum level of patients with unruptured aneurysms is significantly lower than
      that of patients with SAH (p < 0.01), while the mean serum level of alpha 1-AT in
      controls does not significantly differ from other groups. The mean serum level of
      alpha 1-AT in patients admitted > 48 h after SAH is significantly higher than
      that of patients admitted within 48 h after the haemorrhage (p < 0.02).
      Considering the smoking habit of patients, there is no significant difference in
      alpha 1-AT levels in each subgroup of patients. A multivariate analysis
      considering alpha 1-AT CIC, showed that alpha 1-AT CIC in patients with ruptured
      aneurysms is significantly reduced if compared to controls and unruptured
      aneurysms (F = 50.759; p < 0.001). Moreover, considering alpha 1-AT CIC and
      smoking habit in each group the covariance analysis showed that while in controls
      and unruptured aneurysms there is no difference in alpha 1-AT CIC between smokers
      and non smokers, in cases of SAH, cigarette smoking significantly influences the
      alpha 1-AT CIC. The present results suggest that the basic mechanism behind the
      increased risk of SAH in smokers involves a qualitative deficiency of alpha 1-AT.

PMID- 8880690
TI  - Neurotransmitter amino acids in cerebrospinal fluid of patients with Parkinson's
      disease.
AB  - We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in
      plasma), asparagine, glutamine, glycine and GABA in 31 patients with Parkinson's
      disease and in 45 matched controls. We used an ion-exchange chromatography
      method. When compared to controls, PD patients had similar CSF levels of
      glutamate, glutamine, asparagine, and glycine higher CSF GABA levels higher
      plasma levels of glutamine, asparagine, and glycine, and lower plasma levels of
      aspartate. The CSF levels of the amino acids measured were not correlated with
      the clinical features of PD. Our results that CSF GABA levels are not decreased
      in PD as previously suggested.

PMID- 8880691
TI  - Relationship between cognitive impairments, event-related potentials, and motor
      disability scores in patients with Parkinson's disease: 2-year follow-up study.
AB  - We studied event-related potentials and the cognitive state for 2 years in 29
      patients with Parkinson's disease (PD). Of those patients, 11 were at stage II
      and 18 were at stage III at initial assessment, as measured on the Hoehn and Yahr
      scale. The peak latency of P300 in patients at stage III was significantly
      prolonged, as compared with that in age-matched normal controls or PD patients at
      stage II. There was no significant change in P300 latency among patients whose
      motor ability remained unchanged at stage II or stage III during follow-up
      period. The mean P300 latency prolonged significantly in patients whose motor
      ability worsened from stage III to stage IV. The cognitive state in the patients
      with PD was characterized by impairment in the categories of orientation, recall
      and constructional ability. The degree of impairment of these items increased as
      the motor disability increased. These results suggest that cognitive dysfunctions
      and abnormality of P300 latency increased as the motor disabilities progressed.

PMID- 8880692
TI  - Effect of digitalis on conduction dysfunction in Pelizaeus-Merzbacher disease.
AB  - We studied the effect of digitalis on nerve conduction dysfunction in Pelizaeus
      Merzbacher disease (PMD). The patients were three Japanese boys with PMD, aged 7
      10 years. Digitalis was administered orally in a daily dose of 0.06 mg/kg for 2
      consecutive months, and the obtained serum concentrations ranged from 0.33 to
      0.55 ng/ml. The digitalis therapy induced slight improvement of severe dysarthria
      and cognitive dysfunction in the two older patients. Electrophysiological
      examinations revealed the following results: In brainstem auditory evoked
      potentials (BAEPs), while waves II (or III) to V were absent before treatment, on
      treatment all waves of BAEPs except a wave IV were restored in all patients.
      While visual evoked potentials (VEPs) in response to transient flash stimulation
      showed markedly prolonged latencies before treatment, digitalis produced a mild,
      although not statistically significant, shortening of the latency of N160. There
      were also no significant changes in inter-peak amplitudes of VEPs. Transcranial
      cortical magnetic stimulation continued to fail to elicit motor evoked potentials
      of the first dorsal interosseous muscles in all patients. Thus, although the
      serum concentrations were insufficient to elicit favorable therapeutic effects,
      digitalis therapy provided slight relief of clinical symptoms with evidence of
      improvement of conduction dysfunction. It is suggested that patients with PMD may
      respond to symptomatic treatment modulating nerve conduction.

PMID- 8880693
TI  - Effect of cerebrospinal fluid from normal and Alzheimer's patients with different
      apolipoprotein E phenotypes on in vitro aggregation of amyloid beta-protein.
AB  - We examined the effect of cerebrospinal fluid (CSF) from 23 Alzheimer's disease
      (AD) patients and 22 age-matched non-demented controls with apolipoprotein E4/4,
      3/3, or 3/2 phenotypes on in vitro aggregation of amyloid beta-protein (A beta) 1
      40 by Thioflavin T fluorescence spectroscopy. CSF from both AD and control groups
      inhibited A beta aggregation, as compared to that of phosphate buffered saline,
      in agreement with an earlier report (Wisniewski et al., 1993). However, there was
      significantly less aggregation of A beta in presence of CSF from AD than that
      from non-demented controls. The presence of CSF from controls with apoE3/3
      phenotype resulted in higher A beta aggregation as compared to other phenotypes.
      There was a positive correlation between CSF apoE concentrations and A beta
      aggregation; whereas age, CSF soluble A beta levels or severity of dementia did
      not correlate with A beta aggregation. These results suggest that mechanism of
      sequestration of A beta in CSF may not be defective in AD. Amyloid formation in
      AD may be impact of altered balance of other factors such as amyloid-associated
      proteins/extracellular matrix components that can immobilize A beta in the brain,
      and promote its fibrillogenesis in AD.

PMID- 8880695
TI  - Amyloid beta protein in plasma from patients with sporadic Alzheimer's disease.
AB  - Fibrillar amyloid beta protein (A beta) deposition is increased in the brains of
      patients with Alzheimer's disease (AD), and is manifested as senile plaques (SPs)
      and congophilic angiopathy (CA). A beta 40 and A beta 42(43), two chief species
      of A beta, are documented in SPs and CA, as well as in cerebrospinal fluid (CSF)
      and cell culture media. A beta 42(43) is the major component of diffuse plaques,
      the earliest form of SPs. Thus, we hypothesized that determination of the amount
      of A beta 42(43) in CSF or plasma might provide a diagnostic laboratory test for
      AD. We measured amounts of different A beta species in plasma from 28 patients
      with sporadic probable AD, 40 age-matched neurologic patients without dementia
      and 25 age-matched normal controls using enzyme-linked immunosorbent assays
      (ELISAs). Plasma concentrations of A beta 1-40 and A beta 1-42(43) did not
      significantly differ among these groups. These findings suggest the unlikelihood
      that plasma A beta assays would be useful as a diagnostic tool for AD.

PMID- 8880694
TI  - Propentofylline improves regional cerebral glucose metabolism and
      neuropsychologic performance in vascular dementia.
AB  - In a double-blind, placebo-controlled trial in thirty patients with mild to
      moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of
      the adenosine uptake blocker propentofylline (HWA 285) on regional cerebral
      glucose metabolism (rCMRGl) was studied using positron emission tomography of 2
      [18F]fluoro-2-deoxy-D-glucose (FDG). 25 subjects completed the 3-months study.
      Propentofylline significantly improved relative rCMRGl in the motor cortex, while
      relative rCMRGl in the placebo treated group worsened significantly.
      Neuropsychologically, visual information processing was improved in the
      propentofylline group and we observed a trend towards a slowing of the
      progression of cognitive deterioration in patients with VD. The results of the
      longitudinal analysis showed further that neuropsychological and metabolic
      changes are closely related. These findings justify a large-scale clinical trial
      to prove therapeutic efficacy.

PMID- 8880696
TI  - The antioxidant enzymatic blood profile in Alzheimer's and vascular diseases.
      Their association and a possible assay to differentiate demented subjects and
      controls.
AB  - A study of several elements of the antioxidative system: Cu-Zn superoxide
      dismutase (SOD), catalase (CAT), glutathione system (GLU), chemiluminescence
      (CHE), and antioxidant capacity (AOX), was conducted in 20 demented probable
      Alzheimer's (DAT), and 15 vascular demented (VD) patients, 19 control (C)
      subjects, and 11 relatives (F) of one DAT patient. A significant association was
      found between the variables of the antioxidant system, measured in blood samples,
      and the neurological pathologies VD and DAT: Kruskal-Wallis test; p = 0.0006 (p =
      0.014 when the analysis did not include SOD). This demonstrated that VD and DAT
      diseases are accompanied by oxidative disorders. The VD and DAT diseases are
      differentially distinguishable by changes in blood profiles. A graphical method
      for classification, the Principal Components Analysis (PCA), distinguished
      between demented and non-demented subjects on the basis of their laboratory
      variables. A numerical method, Discriminant Functions (DF), constructed to
      separate the clinical groups on the basis of the same variables, obtained
      relatively high percentages of success: 92% of demented were detected against
      healthy subjects; of the latter 82% have been correctly identified as non
      demented. Discrimination between VD and DAT patients was achieved for 100% of VD
      and 86% of DAT patients. DF were similarly successful in detecting the healthy
      condition of DAT relatives. Possible different mechanisms involved in H2O2
      elimination in DAT and VD patients are proposed, where CAT is the responsible
      enzyme of this reaction in DAT patients, while in VD this function would be
      achieved mainly through the action of GLU. It seems that SOD levels are stable,
      at least, within one year. Variations appear to be linked with clinical changes.

PMID- 8880697
TI  - Language functions in incipient cognitive decline in multiple sclerosis.
AB  - Although the mechanisms of cognitive impairment in multiple sclerosis (MS) have
      been extensively studied, evaluation of language functions has been given little
      attention. In the present study, we evaluated whether impairment of language
      functions is associated with cognitive decline in MS. We studied naming, reading,
      and writing performance of two carefully matched patient groups differing only
      with respect to cognitive status. In language tasks, the patients with incipient
      cognitive decline not only demonstrated performance slowness but also made more
      errors than the patients with preserved cognitive capacity and the healthy
      controls. The comprehensive naming error analysis revealed that the cognitively
      deteriorated patients produced error types not present in the other two study
      groups. Contrary to previous suggestions, the present study indicates that
      impaired language performances in MS are attributable to mild cognitive
      deterioration rather than to sensory or motor factors. Thus, assessment of
      language functions should be included in neuropsychological evaluations of MS
      patients.

PMID- 8880698
TI  - Lack of influence of histopathological changes on carbamazepine and carbamazepine
      10, 11-epoxide concentrations in the brain cortex of epileptic patients.
AB  - Post-mortem concentrations of carbamazepine (CBZ) and its anticonvulsive
      metabolite carbamazepine-10,11-epoxide (CE) were determined in different lesions
      of the cerebral cortex and in the serum (total and free) from 13 epileptic
      patients. Twenty cortical specimens were obtained from the superior frontal
      gyrus, the temporopolar region and the neocerebellum. The cortical samples showed
      various pathological changes characterized by augmented glial cells, fibre
      gliosis or ulegyria as well as abundant corpora amylacea or encephalitic signs of
      viral type besides neuronal depletion. The CBZ and CE concentrations in the 20
      cortical lesions were not significantly decreased when compared to the control
      specimens of 32 epileptic patients without essential histopathological
      alterations of the specified cortical areas (p < 0.05). A comparable result had
      been found in our former study on phenytoin (PHT) and phenobarbital (PB). Six
      patients with cortical lesions of the present series had already been included in
      this PHT/PB study. Five of these patients revealed unchanged CBZ and CE as well
      as PHT and PB concentrations. Only in one neocerebellar specimen the CE
      concentration was just above the upper 95% confidence limit of the control group.
      But, most probably this finding has no further relevance. The results greatly
      favour the nonspecific binding of CBZ and CE to cerebral tissue constituents.

PMID- 8880700
TI  - Aging and superoxide dismutase activity in cerebrospinal fluid.
AB  - We investigated superoxide dismutase (SOD) activity in human cerebrospinal fluid
      (CSF) as an index of the aging process in the central nervous system (CNS). The
      subjects were 61 individuals aged 21-77 years, comprising 24 men and 37 women
      without organic disorders of the nervous system. SOD activity in CSF was measured
      by the nitrite method modified by Oyanagui. The results showed that SOD activity
      in CSF gradually increased with age and that the values of SOD activity after the
      fifth decade were significantly higher than those in the third and fourth
      decades. It might suggest that the productivity of SOD in the CNS gradually
      increased with age due to stimulation of various types of oxidative stress which
      accumulated in vivo especially after the fifth decade.

PMID- 8880699
TI  - Muscle phosphofructokinase deficiency in two generations.
AB  - Phosphofructokinase (PFK) is the key regulatory enzyme of glycolysis. Patients
      lacking the muscular isoform of PFK typically present with myopathy and
      compensated hemolysis (glycogenosis type VII or Tarui's disease). Since 1965
      about 30 cases of muscular PFK deficiency have been reported. In most cases
      family history suggests a recessive inherited trait. We describe a family of
      Ashkenazi Jewish origin with two members in subsequent generations suffering from
      muscular PFK deficiency. The propositus, a 19-year-old male patient presented
      with weakness, myalgias and exercise intolerance since early infancy. His father
      also had early fatigue on exercise with myalgias; the mother and a 12-year-old
      brother were asymptomatic. Muscle biopsy of both the propositus and his father
      showed increased glycogen storage and absent histochemical stain for PFK.
      Biochemical studies of muscle revealed a markedly decreased PFK activity and DNA
      analysis of the muscle PFK gene revealed compound heterozygosity in both cases.
      This is the first description of proven muscle PFK deficiency (glycogenosis type
      VII) in two subsequent generations.

PMID- 8880701
TI  - Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI
      analyses of vascular cases.
AB  - Micturitional histories were taken from 39 patients with acute brainstem stroke.
      Within 3 months from onset, 49% had irritative as well as obstructive urinary
      symptoms, the most common being voiding difficulty and nocturnal urinary
      frequency in 28%, followed by urinary retention in 21%. Urodynamic studies of 11
      symptomatic patients revealed detrusor hyperreflexia in 73%, low compliance
      bladder in 9%, atonic cystometrogram in 27%, detrusor-sphincter dyssynergia in
      45% and uninhibited sphincter relaxation in 27%. Three asymptomatic patients had
      normal urodynamic findings. Brain magnetic resonance images of the lesions of the
      symptomatic patients were concentrated in the dorsolateral pons including pontine
      reticular nucleus and the reticular formation adjacent to the medial parabrachial
      nucleus and the locus coeruleus. These regions seem to be mainly responsible for
      supranuclear types of pelvic and pudendal nerve dysfunction in our patients with
      brainstem stroke, corresponding to the pontine urinary storage and micturation
      center reported in animal studies.

PMID- 8880702
TI  - Benign monomelic amyotrophies of upper and lower limb are not associated to
      deletions of survival motor neuron gene.
AB  - Benign monomelic amyotrophies (BMAs) are rare conditions in which neurogenic
      atrophy is restricted either to the upper or lower limb. BMAs are usually
      sporadic, have insidious onset and slow progression followed by stabilization,
      are clinically confined for many years to a single limb and lack of sensory,
      bulbar, and pyramidal signs. Although the aetiology and pathogenesis of BMAs are
      unknown they are considered variants of spinal muscular atrophy with focal
      emphasis and a benign course. We studied 7 patients with BMAs to investigate
      whether they present alterations of the survival motor neuron gene (SMN) which
      has been found deleted or disrupted in proximal spinal muscular atrophy. All 7
      patients showed the presence of both exon 7 and 8 of SMN gene. These findings
      indicate that deletions at the SMN locus are not present in BMA of upper and
      lower limb and suggest that these disorders are not only clinically but also
      genetically separate entities from proximal spinal muscular atrophies.

PMID- 8880704
TI  - Lymphocytic encephalomyeloneuritis as a neurologic complication of ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD)
      showing immunologic abnormalities and association with autoimmune states (Snook
      et al., 1989). Extraintestinal manifestation of UC affect various organ systems
      (Podolsky, 1991). We describe morphologically documented encephalomyeloneuritis
      in a 58-year-old white male with UC in full remission providing support for the
      concept that ulcerative colitis may be complicated by neurologic manifestations
      affecting both the central and peripheral nervous system.

PMID- 8880703
TI  - Vitamin E serum levels are normal in ataxia telangiectasia (Louis-Bar disease).
AB  - In order to study the role of vitamin E in the pathogenesis of ataxia
      telangiectasia, we analysed vitamin E serum levels in five children with this
      disorder. No differences with respect to controls were found. However, these
      negative results do not exclude that abnormal vitamin E metabolism may be present
      at the cellular level.

PMID- 8880705
TI  - A Japanese case of Creutzfeldt-Jakob disease with a point mutation in the prion
      protein gene at codon 210.
AB  - We screened 111 cases of sporadic Creutzfeldt-Jakob disease (CJD) and 75 healthy
      control subjects in Japan to detect possible polymorphisms in their prion protein
      gene (PRNP). We identified a G-to-A point substitution at codon 210, leading a
      valine-to-isoleucine change, in a 69-year-old CJD patient. This substitution was
      not seen in 75 healthy control subjects.

PMID- 8880706
TI  - Idiopathic dural herniation of the thoracic spinal cord.
AB  - Symptomatic anterior or anterolateral dural herniation of the spinal cord is
      rare, and not uncommonly misdiagnosed, both clinically and radiologically. We
      present four patients with a radiological diagnosis of herniation of the thoracic
      spinal cord, and review the current literature. All affected patients have been
      adults, typically presenting with long-standing, unexplained sensory symptoms and
      eventually developing a Brown-Sequard syndrome, with or without motor changes.
      Herniation occurs in the upper or midthoracic region, between the T2 and T8
      levels.

PMID- 8880707
TI  - MRI of the spine in cobalamin deficiency: the value of examining both spinal cord
      and bone marrow.
AB  - We observed a case of pernicious anaemia in which MRI of the spine demonstrated
      both intrinsic lesions of the spinal cord and abnormal signal in the bone marrow.
      The latter resolved with replacement therapy. Only partial recovery of the cord
      lesions was observed.

PMID- 8880708
TI  - MRI of enlarged dorsal ganglia, lumbar nerve roots, and cranial nerves in
      polyradiculoneuropathies.
AB  - This paper describes the MRI findings in four patients with a clinical diagnosis
      of hypertrophic polyradiculoneuropathies. In two examination of the lumbar spine
      showed enlarged nerve roots and dorsal ganglia, and similar findings were present
      in the cervical spine in a third. The cisternal portions of the cranial nerves
      were enlarged in another patient. MRI allows identification of enlarged nerves in
      hypertrophic polyradiculopathies.

PMID- 8880709
TI  - Vascular complications in lumbar disk surgery: report of four cases.
AB  - Vascular injuries in lumbar disk surgery, although rare, are serious
      complications which may be overlooked due to a broad range of clinical
      manifestations. It is important that surgeons and radiologists be aware of these
      potentially fatal complications and develop an appropriate symptom-based
      diagnostic paradigm. We reviewed 8099 consecutive cases of lumbar disk surgery,
      performed over a 14-year period at a single institution, for postoperative
      vascular complications. We identified four patients (0.05%) with lumbar disk
      surgery-related vascular complications: intraoperative lacerations of the
      abdominal aorta and median sacral artery, an arteriovenous fistula between the
      left common iliac artery and vein detected 19 days postdiskectomy, and a
      partially thrombosed aortic aneurysm with an arteriovenous fistula between the
      aneurysm and the inferior vena cava, diagnosed 11 months after surgery. The
      majority of cases in the literature of vascular injury in lumbar disk surgery
      were reported prior to 1965. Diagnostic approaches described in that period do
      not reflect the great range of diagnostic techniques available today. Angiography
      remains the gold standard for diagnosis and guidance as to surgical repair.
      However, a high index of suspicion based on clinical signs and/or the use of
      sonography or CT is important in the detection of these complications.

PMID- 8880710
TI  - Epidermoid cyst of the conus medullaris: atypical MRI and angiographic features.
AB  - We report a 50-year-old man with an epidermoid cyst of the conus medullaris which
      showed a nodular gadolinium enhancement on MRI and a blush on angiography. These
      radiological features are compared with pathological examination.

PMID- 8880711
TI  - Lhermitte-Duclos disease associated with syringomyelia.
AB  - A 23-year-old man presented with a 2-week history of intracranial hypertension.
      CT showed a large, nonenhancing cerebellar mass with surrounding calcification
      and displacement of the fourth ventricle. MRI revealed a septate lesion, with low
      signal on T1-weighted and high signal on T2-weighted images. The cerebellar
      tonsils were displaced below the foramen magnum and there was associated
      syringomyelia. The MRI features were characteristic of Lhermitte-Duclos (LD)
      disease (dysplastic gangliocytoma) and the diagnosis was confirmed following
      surgery. In this case, we emphasise the usefulness of MRI in the diagnosis of LD
      disease and consider the possible pathogenesis of the associated syringomyelia.

PMID- 8880712
TI  - Radiographic type I autosomal dominant osteopetrosis with syringohydromyelia.
AB  - A case of radiographic type I benign osteopetrosis with syringohydromyelia is
      presented. MRI revealed diffuse sclerosis of the bone marrow in the thick cranial
      bones and narrowing of the foramen magnum and subarachnoid spaces, especially in
      the posterior cranial fossa, and syringohydromyelia.

PMID- 8880713
TI  - Cerebral venous thrombosis after myelography with iopamidol.
AB  - A young man developed intracranial hypertension immediately after myelography
      with non-ionic water-soluble contrast medium (iopamidol). Cerebral angiography
      showed extensive cerebral venous thrombosis. The common causes of
      thrombophlebitis were excluded. A relationship to the contrast medium was
      strongly suspected, since a similar case has been reported. The rheological
      properties and haemo-concentration induced by iopamidol could explain this
      complication.

PMID- 8880714
TI  - Evaluation of the clinical safety of gadodiamide injection, a new nonionic MRI
      contrast medium for the central nervous system: a European perspective.
AB  - Gadodiamide injection is a new nonionic paramagnetic, extracellular contrast
      medium. Its safety at a dose of 0.1 mmol/kg body weight was evaluated in a large
      European multicentre trial on adults referred for contrast-enhanced MRI of the
      central nervous system. Safety analysis was performed on 2102 patients, in whom
      adverse events during and up to 24 h after injection were recorded. Adverse
      events related or possibly related to gadodiamide injection were observed in 102
      patients. Injection-associated reactions classified as discomfort (sensation of
      heat or coldness, pain or pressure at the injection site) occurred in 37 patients
      (1.8%) and other adverse events (e.g. headache, nausea) were observed in 65
      patients (3.1%). No serious adverse event was reported. Efficacy analysis,
      performed on 2273 patients, and based on comparison of T1- and T2-weighted images
      before and T1-weighted images after injection showed that more diagnostic
      information was obtained after gadodiamide injection in 1424 (62.6%) patients:
      management of 386 (17.0%) patients was affected by the new information given and
      that a new diagnosis was made in 755 (33.3%) patients. Gadodiamide injection was
      shown to be safe and well tolerated. It represents a nonionic alternative to the
      current products for MRI of the central nervous system.

PMID- 8880715
TI  - Comparative study of CT and MRI in patients with seizures and a solitary cerebral
      cysticercus granuloma.
AB  - We hypothesized that when contrast-enhanced CT reveals a solitary cerebral
      cysticercus granuloma, MRI would not usually provide additional information that
      might assist in management. We retrospectively compared visualisation of solitary
      cysticercus granulomas on contrast-enhanced CT and MRI in 16 patients presenting
      with seizures; gadolinium (Gd) enhancement was used in 6 patients. The granuloma
      was delineated well on both CT and MRI in 15 patients; in one patient, in whom CT
      was performed with 10-mm slices, it was seen only on contrast-enhanced MRI, CT
      and unenhanced MRI revealing only the surrounding oedema. On CT the granuloma was
      seen best on thin (2-5 mm) contrast-enhanced sections (in 10 patients). On MRI,
      Gd-enhanced images showed the granuloma best, as a ring-enhancing lesion, in all
      6 patients. In the other 10 patients, the granuloma was seen only on T2-weighted
      images in 8 and on both T1- and T2-weighted images in 2. On T2-weighted images a
      characteristic low-signal ring with a high-signal centre was seen in 12 patients.
      Sensitivity of the imaging techniques was: contrast-enhanced CT (5 and 10 mm
      slices) 93.8% (15/16); thin (2-5 mm) section contrast-enhanced CT 100% (6/6);
      unenhanced MRI 93.8% (15/16). MRI did not reveal additional granulomas or cysts
      in any patient. In patients strongly suspected to be harbouring this lesion, when
      10-mm contrast-enhanced CT reveals only oedema, thin (2-5 mm) slice CT is a cost
      effective alternative to MRI.

PMID- 8880716
TI  - The "target sign": is it a specific sign of CNS tuberculoma?
AB  - In brain lesions, the target sign has been defined as a central nidus of
      calcification or central enhancement surrounded by a ring of enhancement. It has
      been considered a pathognomonic finding of central nervous system (CNS)
      tuberculoma. The purpose of this report is to demonstrate that the target sign
      related to central enhancement is a nonspecific finding and may lead to erroneous
      diagnosis of CNS tuberculoma.

PMID- 8880717
TI  - Chronic encapsulated intracerebral haematomas.
AB  - We present four patients with uncommon encapsulated intracerebral haematomas
      (ICH). Because of ring enhancement, three were incorrectly diagnosed as gliomas
      and operated upon. In one case the diagnosis of chronic ICH was made on MRI. MRI
      can be used to demonstrate that a lesion is only a haematoma and is valuable in
      follow-up and in differentiating these haematomas from neoplasms. Angiography may
      reveal a vascular malformation which may be the reason for repeated bleeding,
      which may lead to encapsulation. The mechanism, however, remains unclear in most
      cases.

PMID- 8880718
TI  - Visualisation of intracranial aneurysms by transcranial duplex sonography.
AB  - We examined 72 patients with 89 angiographically confirmed intracranial
      aneurysms, using transcranial colour-coded duplex sonography (TCCD) to determine
      the location and size of the aneurysm. The patients were admitted for coil
      embolisation of their aneurysm following subarachnoid haemorrhage or because of a
      cranial nerve palsy. Using a 2/2.25 MHz transducer, 42 aneurysms (47%) were seen
      satisfactorily through the temporal bone window or foramen magnum. In 24 cases
      (27%) image quality was insufficient as a result of a poor bone window, of the
      aneurysm having a diameter of less than 6 mm or of its being in an unfavorable
      location. In 23 other cases (26%) it was not possible to detect the aneurysm.
      Thrombosed structures could be demonstrated using TCCD in 8 of 12 giant
      intracavernous or basilar artery aneurysms, and in 15 of 19 aneurysms treated by
      platinum coil embolisation. TCCD offers a noninvasive method for monitoring
      progressive intra-aneurysmal thrombosis following coil embolisation and for
      follow-up of patients with untreatable fusiform aneurysms, should this be
      required. Detection of small aneurysms is limited by spatial resolution and
      insonation angles.

PMID- 8880719
TI  - Tumefactive demyelinating lesions.
AB  - We studied 21 cases of pathologically confirmed tumefactive demyelinating lesions
      and reviewed the spectrum of tumefactive demyelinating lesions in the literature.
      Radiological features and clinical data were reviewed to characterize the lesions
      as consistent with a known demyelinating disease, most notably multiple
      sclerosis. Atypical clinical or radiological features (other than tumefaction)
      were noted. Most lesions were part of a clinical and/or radiological picture
      consistent with multiple sclerosis. No case strongly suggestive of variants or
      related diseases, such as Schilder's disease or Balo's concentric sclerosis, were
      found. There was one case suggestive of acute disseminated encephalomyelitis.
      Features which help distinguish the lesions from tumour are discussed.

PMID- 8880720
TI  - Contrast-enhanced MRI of intrasellar arachnoid cysts: relationship between the
      pituitary gland and cyst.
AB  - We recently encountered two large intrasellar arachnoid cysts extending to the
      suprasellar region. The intensity of the cyst contents was identical to that of
      the cerebrospinal fluid on both T1- and T2- weighted MRI. On contrast-enhanced
      MRI, the pituitary gland was compressed posteroinferiorly and flattened in the
      sella turcica. In this report of rare intrasellar arachnoid cysts the discussion
      is focused on dislocation of the pituitary gland.

PMID- 8880721
TI  - Intradiploic arachnoid cyst: case report.
AB  - Because of the extreme rarity of intradiploic arachnoid cysts, their pathogenesis
      is unknown; congenital or traumatic origins are suggested. We report an
      intradiploic arachnoid cyst in a 57-year-old woman, without a history of trauma,
      in whom a forgotten injury might play a significant role.

PMID- 8880722
TI  - Three-dimensional chemical shift-selective MRI of a ruptured intracranial dermoid
      cyst.
AB  - We report a man with a ruptured intracranial dermoid cyst, suffering from
      headache, nausea, vomiting and a generalised seizure. MRI was performed before
      and 2 weeks after surgical resection. On T1-weighted images the tumour gave high
      signal, as did fatty material in the frontal and parietal brain sulci.
      Identification of this hyper-intense material as lipids was possible by chemical
      shift-selective 3D gradient-echo imaging, which provided excellent contrast
      between the subarachnoid lipids and the adjacent normal brain, with a good
      spatial resolution. Possible complications of subarachnoid and intraventricular
      lipid particles after dermoid cyst rupture are discussed and the diagnostic value
      of 3 D chemical-shift-selective additional to conventional T-1-weighted spin-echo
      images in identification of even small amounts of fat is emphasised.

PMID- 8880723
TI  - Deep cerebral invasion by basal cell carcinoma of the scalp.
AB  - We report recurrent basal cell carcinoma of the scalp with deep cerebral invasion
      in an 82-year-old man. Plain films and CT showed extensive, full thickness, skull
      destruction at the vertex. Gadolinium-enhanced MRI revealed neoplastic invasion
      of the meninges and left cerebral hemisphere, down to the lateral ventricle. We
      postulate that tumour extended into the brain along perivascular spaces of
      transcerebral vessels. This hypothesis is supported by the cleft-like contrast
      enhancement on MRI.

PMID- 8880724
TI  - MR signal intensity of the perirolandic cortex in the neonate and infant.
AB  - Our purpose was the study the magnetic resonance (MR) signal intensity of the
      perirolandic gyri perinatally and to correlate it with the histological findings
      in formalin-fixed brains, focusing on myelination. MRI of 20 neurologically
      normal neonates and infants, of 37-64 weeks postconception (PCA), were studied
      retrospectively. We reviewed four formalin-fixed brains of infants 37-46 weeks
      PCA microscopically. The posterior cortex of the precentral gyrus (P-PRE) and the
      anterior cortex of the postcentral gyrus (A-PST) had different signal intensity
      from the adjacent surrounding cortex. On T1-weighted images P-PRE and A-PST gave
      higher signal 41-44 weeks PCA; on T2-weighted images, they gave lower signal 37
      51 weeks PCA. Histological examination revealed very little myelination of the
      nerve fibres within both the P-PRE and the A-PST, while considerable myelination
      was present in the internal capsule and central corona radiata. The changes in
      signal intensity in the perirolandic gyri may reflect not only the degree of
      myelination but also the more advanced development of the nerve cells, associated
      with rapid proliferation and formation of oligodendroglial cells, synapses and
      dendrites. They could be another important landmark for brain maturation.

PMID- 8880726
TI  - Transcranial cerebral oximetry in endovascular treatment of carotid-cavernous
      fistula.
AB  - The transcranial cerebral oximeter is a reliable, low-cost, noninvasive device
      that provides real-time evaluation of regional brain oxygen saturation during
      endovascular treatment of cerebrovascular diseases. We discuss three patients
      with carotid-cavernous fistulae treated by endovascular balloon occlusion, each
      monitored continuously before, during, and after the procedure with transcranial
      cerebral oximetry. The cerebral oxygen saturation measured was directly related
      to the side of the venous drainage of the fistula, being 15-20% higher on that
      side. Following endovascular occlusion of the fistula, oxygen saturation
      gradually became equal on the two sides.

PMID- 8880725
TI  - Vertebral haemangiomas with spinal cord compression: the place of preoperative
      percutaneous vertebroplasty with methyl methacrylate.
AB  - We report on cervical and two thoracic vertebral haemangiomas with neurological
      disturbance successfully treated by percutaneous vertebroplasty followed by
      decompression surgery. Vertebroplasty consolidates the vertebral body and reduces
      the risk of haemorrhage. Subsequent surgery may be limited to decompressive
      laminectomy and resection of the epidural extension of the haemangioma.
      embolisation was also carried out in one case. Complete neuroimaging workup,
      including CT, myelo-CT and MRI, is necessary prior to treatment.

PMID- 8880727
TI  - Ehlers-Danlos syndrome with a spontaneous caroticocavernous fistula occluded by
      detachable balloon: case report and review of literature.
AB  - We report a caroticocavernous fistula (CCF) treated by an endovascular procedure
      in a young woman with Ehlers-Danlos syndrome type IV, with severe bilateral
      carotid and vertebral artery dysplasia. The CCF, which appeared after minor
      trauma, was successfully occluded by a detachable balloon introduced into the
      venous side by an arterial approach. Six previously published cases are reviewed,
      five successfully treated. The difficulties and risks of the endovascular
      procedure due to the vascular changes, are emphasised. The possibility of the
      venous approach is discussed.

PMID- 8880728
TI  - Behavioral consequences of intracerebral vasopressin and oxytocin: focus on
      learning and memory.
AB  - Since the pioneering work of David de Wied and his colleagues, the neuropeptides
      arginine vasopressin and oxytocin have been thought to play a pivotal role in
      behavioral regulation in general, and in learning and memory in particular. The
      present review focuses on the behavioral effects of intracerebral arginine
      vasopressin and oxytocin, with particular emphasis on the role of these
      neuropeptides as signals in interneuronal communication. We also discuss several
      methodological approaches that have been used to reveal the importance of these
      intracerebral neuropeptides as signals within signaling cascades. The literature
      suggests that arginine vasopressin improves, and oxytocin impairs, learning and
      memory. However, a critical analysis of the subject indicates the necessity for a
      revision of this generalized concept. We suggest that, depending on the
      behavioral test and the brain area under study, these endogenous neuropeptides
      are differentially involved in behavioral regulation; thus, generalizations
      derived from a single behavioral task should be avoided. In particular, recent
      studies on rodents indicate that socially relevant behaviors triggered by
      olfactory stimuli and paradigms in which the animals have to cope with an intense
      stressor (e.g., foot-shock motivated active or passive avoidance) are controlled
      by both arginine vasopressin and oxytocin released intracerebrally.

PMID- 8880729
TI  - Neuropsychiatric aspects of cytokines research: an overview.
AB  - Cytokines are a group of proteins primarily synthesized by various immune cells.
      They have multiple functions within the immune system and have been implicated in
      a number of disease states. There is growing evidence that some cytokines are
      also synthesized in the central nervous system. Taking into consideration that
      some cytokines are also capable of inducing behavioral effects, it has been
      suggested that cytokines may play a role in some psychiatric and neurologic
      disorders.

PMID- 8880730
TI  - The transition from slow-wave sleep to paradoxical sleep: evolving facts and
      concepts of the neurophysiological processes underlying the intermediate stage of
      sleep.
AB  - Paradoxical sleep in rats, cats and mice is usually preceded and sometimes
      followed by a short-lasting (a few seconds) electroencephalogram (EEG) stage
      characterized by high-amplitude spindles in the anterior cortex and low-frequency
      theta rhythm in the dorsal hippocampus. The former is an index of advanced slow
      wave sleep; the latter is an index of limbic activation since it occurs during
      active waking and paradoxical sleep. Barbiturates and benzodiazepines extend this
      intermediate stage at the expense of paradoxical sleep while concomitantly
      barbiturates suppress the pontine reticular activation characteristic of this
      sleep stage. During the intermediate stage, thalamocortical responsiveness and
      thalamic transmission level, which are controlled by brain stem activating
      influences, are the lowest of all sleep-waking stages. The unusual EEG pattern of
      this stage is otherwise only observed in the acute intercollicular-transected
      preparation. Therefore, forebrain structures may be functionally briefly
      disconnected from the brain-stem during this short-lasting stage, which could
      possibly account for the mental content of a similar sleep period in humans. In
      spite of strong evidence in favour of this forebrain deafferentiation hypothesis,
      other data indicate that the IS is in some way linked either to slow-wave sleep
      or to paradoxical sleep.

PMID- 8880731
TI  - Malnutrition and reactivity to drugs acting in the central nervous system.
AB  - There is a well-established body of data demonstrating that protein or protein
      calorie malnutrition experienced early in life is associated with
      neuroanatomical, neurochemical, as well as behavioral alterations in both animals
      and humans. A number of studies has focused on the following question: are the
      neuroanatomical and/or neurochemical changes produced by early malnutrition
      responsible for the altered behaviors reported in malnourished animals? A tool
      that has been used to help answer this question is the administration of drugs
      with specific actions in the various neurotransmitter systems in the central
      nervous system (CNS). This neuropharmacological approach has produced a
      considerable amount of data demonstrating that malnourished animals react to
      drugs differently from controls, suggesting that the altered behavioral
      expression of these animals could be partly explained by the alterations in the
      brain function following malnutrition. The present review will provide an
      overview of the literature investigating the reactivity of malnourished animals
      to psychoactive drugs acting through GABAergic, catecholaminergic, serotonergic,
      opioid and cholinergic neurotransmitter systems. Altered responsiveness to
      psychoactive drugs in malnourished animals may be especially relevant to
      understanding the consequences of malnutrition in human populations.

PMID- 8880732
TI  - Melatonin effects on behavior: possible mediation by the central GABAergic
      system.
AB  - The best described function of the pineal hormone melatonin is to regulate
      seasonal reproduction, with its daily production and secretion varying throughout
      the seasons or the photoperiod. Additionally, a number of behavioral effects of
      the hormone have been found. This review describes the effects of melatonin in
      rodent behavior. We focus on: (a) inhibitory effects (sedation, hypnotic
      activity, pain perception threshold elevation, anti-convulsive activity, anti
      anxiety effects); and (b) direct effects on circadian rhythmicity (entrainment,
      resynchronization, alleviation of jet-lag symptoms, phase-shifting). Most of
      these effects are clearly time-dependent, with a peak of melatonin activity
      during the night. One of the possible mechanisms of action for melatonin in the
      brain is the interaction with the GABAergic system, as suggested by neurochemical
      and behavioral data. Finally, some pineal hormone effects might be candidates as
      putative therapies for several human disorders.

PMID- 8880733
TI  - Studies on the regulation of food intake using rat total parenteral nutrition as
      a model.
AB  - Total parenteral nutrition (TPN) is essential for maintaining the nutritional
      status of patients who are unable to eat sufficiently to meet their metabolic
      needs. However, TPN suppresses appetite and ultimately diminishes food intake.
      Theories concerning the role(s) of peripheral metabolites as signals, acting via
      the liver and the hypothalamus, for the metabolic control of food intake, have
      been put forward to explain the anorectic effect of TPN. In addition, it is
      postulated that changes in peripheral metabolites during TPN may be translated
      into changes in the levels of brain neurotransmitters known to decrease food
      intake. This review summarizes studies concerning the effect of TPN on food
      intake. These studies have involved: (1) characterizing the changes in feeding
      activity due to TPN; (2) investigating the involvement of the central nervous
      system; and (3) investigating the role of the periphery and its metabolites in
      the regulation of food intake during TPN. Some insight into the mechanism of
      action of TPN on food intake is provided.

PMID- 8880734
TI  - The role of inflammation and cytokines in brain injury.
AB  - The original notion that the brain represented an "immune-privileged" organ
      lacking the capability to produce an inflammatory response to an injury, would
      appear no longer tenable. Indeed, accumulating evidence during the last decade
      has shown that the CNS can mount a well-defined inflammatory response to a
      variety of insults including trauma, ischemia, transplantation, viral infections,
      toxins as well as neurodegenerative processes. Many aspects of this centrally
      derived inflammatory response parallel, to some extent, the nature of such a
      reaction in the periphery. Through the recent application of molecular biological
      techniques, new concepts are rapidly emerging as to the molecular mechanisms
      associated with the development of brain injury. In particular, the importance of
      cytokines, especially TNF alpha and IL-1 beta, as well as adhesion molecules, has
      been emphasized in the propagation and maintenance of a CNS inflammatory
      response. This review will summarize recent observations as to the involvement of
      these inflammatory mediators in CNS injury and lay claim to the possibility that
      inhibitors of peripheral inflammation may also be of benefit in treating CNS
      injuries such as stroke, head trauma, Alzheimer's disease and multiple sclerosis.

PMID- 8880736
TI  - Behavioral, structural and neurochemical asymmetries in the avian brain: a model
      system for studying visual development and processing.
AB  - The emphasis of this review is on the visual systems and lateralized visually
      guided behavior in several avian species. Lateral asymmetry is known to be
      present in the tectofugal visual projections to the forebrain of the pigeon and
      in the thalamofugal visual projections to the forebrain of the chicken. These
      structural asymmetries are discussed in the context of the behavioral and
      neurochemical asymmetries. While recognizing the need to investigate the
      organization of both of the visual pathways within one avian species; this review
      reasons inductively that the lateralized organization of the two visual pathways
      leads to binocular input to the right hemisphere via the thalamofugal visual
      system and to the left hemisphere via the tectofugal visual system. For each
      system, input to the other hemisphere is primarily monocular. This specialization
      of the hemispheres for visual processing has predictable effects on behavior. The
      role of asymmetrical light stimulation of the eyes of the embryo in determining
      the lateralizations in the visual pathways and some behaviors is discussed, as
      are other lateralizations generated or altered by imprinting and passive
      avoidance learning.

PMID- 8880735
TI  - Functional and molecular differentiation of the dopamine system induced by
      neonatal denervation.
AB  - The administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to damage the
      mesostriatal dopamine (DA) system in the neonate results in different
      neurochemical and behavioral consequences as compared to lesions made in
      adulthood. There have been few direct data to support the conclusion that the
      behavioral changes following neonatal 6-OHDA lesions reflect plasticity of the DA
      system. It is our hypothesis that the plasticity of the developing DA system is
      fundamentally different from that of the adult. Responses to 6-OHDA lesions can
      only be understood within the context of the status of the mesostriatal DA system
      at the time of the lesion. There are stages of development in the early postnatal
      period when certain components of the mesostriatal DA system are differentially
      sensitive to 6-OHDA lesions. These "windows" of vulnerability can be predicted
      from an analysis of the developmental expression of DA receptors and the
      maturation of the subpopulation of the mesostriatal DA system that innervates
      them. We review the differences in the behavioral plasticity of the adult and
      neonate sustaining 6-OHDA lesions to the mesostriatal DA system, the mechanisms
      responsible for the behavioral plasticity in the adult, and our conceptualization
      of which mechanisms are affected in the neonate.

PMID- 8880737
TI  - Locating reward cue at response manipulandum (CAM) induces symptoms of drug
      abuse.
AB  - Appetitive instrumental discrimination learning procedures provide for CAM (cue
      and manipulandum) when the reward cue (discriminative stimulus positively
      correlated with positive reinforcement) is located at the response manipulandum
      (object that when contacted or manipulated defines the performance of the
      instrumental response). Evidence reviewed shows that CAM induces excessive and
      compulsive instrumental responding relative to otherwise comparable non-CAM
      control procedures. In humans, symptoms of drug abuse are particularly likely
      when the drug-taking implement (response manipulandum at which instrumental drug
      taking is directed) is also predictive of the drug's rewarding effects (reward
      cue). Evidence that the predictive relationship between a drug-taking implement
      and drug reward relates to drug abuse is reviewed, and implications for treatment
      and prevention are considered. CAM is related to neurobiological models of drug
      abuse that emphasize the role of the neurotransmitter dopamine (DA). CAM produces
      convergence of DA-mediated responding for conditioned reinforcement with DA
      mediation of psychomotor activation and incentive-motivational processes to yield
      reflexive cue-directed responding not observed in non-CAM controls.

PMID- 8880738
TI  - Astrocyte-neuron interaction during one-trial aversive learning in the neonate
      chick.
AB  - During two specific stages of the Gibbs-Ng model of one-trial aversive learning
      in the neonate chick, we have recently found unequivocal evidence for a crucial
      involvement of astrocytes. This evidence is metabolic (utilization of the
      astrocyte-specific energy store, glycogen, during normal learning and inhibition
      of memory formation by the astrocyte specific metabolic inhibitors, fluoroacetate
      and methionine sulfoximine) as well as physiological (abolition of memory
      formation in the presence of ethacrynic acid, an astrocyte-specific inhibitor of
      cellular reaccumulation of potassium ions). These findings are discussed in the
      present review in the framework of a more comprehensive description of metabolic
      and physiological neuronal-astrocytic interactions across an interstitial
      (extracellular) space bounded by minute processes from either cell type.

PMID- 8880739
TI  - Salt loading abolishes osmotically stimulated vasopressin release within the
      supraoptic nucleus.
AB  - Central and systemic osmotic stimulation increase vasopressin (VP) release within
      the supraoptic nucleus (SON) and into the general circulation. We examined
      whether changes in water/electrolyte balance affect the neurosecretory responses
      to these stimuli. Urethane-anesthetized control, salt-loaded (2% NaCl for 2 days)
      or water-deprived (for 2 days) male rats were implanted with an arterial catheter
      and bilateral microdialysis probes into the SON. Plasma and SON VP levels were
      measured before and after acute osmotic stimuli were administered
      intraperitoneally (i.p.) and then directly into the SON. Water deprivation
      resulted in elevated basal intranuclear and plasma VP levels. Intraperitoneal
      hypertonic saline (HS) and direct osmotic stimulation of the SON increased VP
      release into the SON in both the control and water-deprived groups. Salt loading
      abolished the intranuclear VP response to both stimuli. Osmotically induced
      release of VP into plasma was not different between the three groups. These data
      demonstrate that salt loading, but not water deprivation, alters the central
      neurosecretory VP response to acute osmotic stimulation.

PMID- 8880740
TI  - Ketamine enhances local anesthetic and analgesic effects of bupivacaine by
      peripheral mechanism: a study in postoperative patients.
AB  - Patients with unilateral (n = 14) and bilateral (n = 4) herniorrhaphy
      participated in this study. With bilateral herniorrhaphy, at the end of the
      surgery, the wound was infiltrated with a solution of bupivacaine 0.5% and
      ketamine 0.3% on one side and a solution of bupivacaine 0.5% only, on the other.
      With unilateral herniorrhaphy, the patients were randomly assigned to one of two
      groups (n = 7). One group at the end of the surgery received the infiltration
      with a solution of bupivacaine 0.5% and ketamine 0.3%, the other group received
      the infiltration with a solution of bupivacaine 0.5% only. The duration of the
      local anesthetic (response to a von Frey filament) and postoperative analgesic
      (time to mild spontaneous pain) effects of the infiltrations, as well as wound
      pain threshold 24 h after surgery (pressure algometry), were determined. In
      patient with unilateral herniorrhaphy, the addition of ketamine for wound
      infiltration enhanced the duration of infiltration anesthesia (206 +/- 76 versus
      343 +/- 108 min, P < 0.02) and analgesia (240 +/- 45 versus 420 +/- 151 min, P <
      0.03). Similar enhancement of the local anesthetic effect was observed in
      patients with bilateral herniorrhaphy. The increase in pain threshold to pressure
      on the wound with the addition of ketamine was evident in bilateral herniorrhaphy
      patients and also with a combination of bilateral and unilateral results (1.39 +/
      0.40 versus 2.35 +/- 0.92 kg, P < 0.02). In the group of five volunteers, the
      subcutaneous infiltration with 0.3% ketamine produced a local anesthetic effect
      lasting only 10-20 min. The results indicate that ketamine acting via a
      peripheral mechanism can profoundly enhance anesthetic and analgesic actions of a
      local anesthetic administered for infiltration anesthesia.

PMID- 8880741
TI  - Separating dual effects of zinc at recombinant N-methyl-D-aspartate receptors.
AB  - The effects of Zn2+ on recombinant N-methyl-D-aspartate (NMDA) receptors
      expressed in Xenopus oocytes were examined. Zn2+ inhibited macroscopic currents
      induced by NMDA at both NR1/NR2B and NR1/NR2A receptors. At NR1/NR2B receptors
      the Zn2+ concentration-inhibition curve was monophasic, with an apparent affinity
      for Zn2/ of 1.6 microM, and inhibition by Zn2+ was not voltage-dependent. In
      contrast, the Zn2+ concentration-inhibition curve at NR1/NR2A receptors was
      biphasic, with high (Ki = 0.08 microM) and low (Ki = 30 microM) affinity
      components. The high affinity component produced a maximal inhibition of 45% of
      macroscopic NMDA currents and was not voltage-dependent. Thus, Zn2+ is more
      potent in producing voltage-independent block at NR1/NR2A than at NR1/NR2B
      receptors, but the maximal effect of Zn2+ is smaller at NR1/NR2A than at NR1/NR2B
      receptors. The low affinity component of Zn2+ inhibition at NR1/NR2A receptors
      was voltage-dependent and may represent an open-channel blocking effect of Zn2+.
      Differential effects of Zn2+ at recombinant NMDA receptors containing different
      NR2 subunits provide a potential marker for distinguishing subtypes of native
      NMDA receptors and for dissecting the site and mechanism of action of Zn2+ at
      these receptors.

PMID- 8880742
TI  - Myosin heavy chain mRNA and protein expression in single fibers of the rat soleus
      following reinnervation.
AB  - Myosin heavy chain (MHC) expression is regulated by many factors including neural
      input. To gain a better understanding of myosin transformation following
      reinnervation we examined both MHC protein and mRNA in single fibers of the
      soleus. A midthigh sciatic nerve lesion resulted in reinnervation of the soleus
      by motoneurons from both original and foreign motor pools. MHC expression was
      examined in individual fibers 8 and 16 weeks post injury in situ histochemistry
      and immunohistochemistry. Following a sciatic nerve lesion, the reinnervated
      soleus underwent a transformation from slow toward fast based on physiologic and
      biochemical measurements. At 8 weeks, fast MHC mRNA isoforms (IIa and IIx) were
      upregulated and slow mRNA was downregulated, however, the predominant protein
      isoform was MHC I. At both 8 and 16 weeks, many fibers expressed multiple mRNA
      isoforms. At 16 weeks there was limited co-expression of slow and fast MHC mRNAs,
      but continued co-expression of fast MHC mRNAs. Sixteen weeks following
      reinnervation the predominant fast mRNA and protein in the soleus was IIx MHC.

PMID- 8880743
TI  - High frequency stimulation of the internal Globus Pallidus (GPi) simultaneously
      improves parkinsonian symptoms and reduces the firing frequency of GPi neurons in
      the MPTP-treated monkey.
AB  - The firing pattern of the neurons of the internal Globus Pallidus (GPi) is
      greatly disturbed in Parkinson's disease. Surgical lesion or high frequency
      stimulation (HFS) of the GPi reduces parkinsonian rigidity and akinesia. We
      evaluated in this study the effects of HFS of the GPi on the firing pattern of
      its neurons. Extracellular recordings were carried out under three types of
      experimental conditions in rhesus monkeys, normal state, after MPTP treatment and
      during HFS of the GPi. After intracarotidian MPTP injection, the firing rate of
      GPi cells increased significantly. During HFS, MPTP-induced parkinsonian motor
      symptoms clearly improved correlatively with a significant decrease in the firing
      rate of GPi cells in the stimulated area. HFS restored a firing frequency similar
      to that in normal animals and, unexpectedly, did not completely block neuronal
      activity.

PMID- 8880744
TI  - Effects of the antiepileptic drug felbamate on long-term potentiation in the CA1
      region of rat hippocampal slices.
AB  - In the CA1 region of rat hippocampal slices, the antiepileptic drug 2-phenyl-1,3
      propanediol dicarbamate (felbamate; 100-1300 microM) concentration-dependently
      decreased extracellularly recorded synaptic potentials. The effect was
      significant at 200 microM, and became maximal at 700 microM felbamate, with a 70%
      decrease in population spike amplitude and 25% reduction of dendritic field
      excitatory postsynaptic potential (fEPSP) slope. Both alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor
      mediated components of the fEPSP were decreased by 700 microM felbamate. Up to
      300 microM felbamate did not affect long-term potentiation (LTP), whereas 500
      microM decreased the magnitude of LTP. Higher concentrations of felbamate (700
      1300 microM) blocked induction of somatic and dendritic LTP completely, but
      reversibly. It appears that the concentrations of felbamate which affect LTP are
      higher than those needed for its antiepileptic action.

PMID- 8880745
TI  - Advances of human core temperature minimum and maximal paradoxical sleep
      propensity by ambient thermal transients.
AB  - By using slow thermal transients of reduced amplitude (+/- 3 degrees C
      (thermoneutrality in humans sleeping nude) during only 1 night (experimental,
      EX), we have advanced the minimum of rectal temperature (Tre) and the peak of
      their paradoxical sleep propensity (PPSP) of sleeping subjects. During this EX
      night Tre minimum was significantly (P = 0.0001) advanced by 143 min versus that
      observed during baseline night spent at thermoneutrality. The advance of PPSP was
      objectivated by the more rapid cumulation of paradoxical sleep (P = 0.02) during
      the second half of EX night, i.e. strictly after the occurrence (around 0330 h)
      of the new Tre minimum, and by the earlier occurrence of its barycentric point (P
      = 0.04) between 0330 and 0700 h. The involvement of the central thermoregulatory
      system on phase-shifting mechanisms is discussed.

PMID- 8880746
TI  - Carnosine-synthesis in cultures of rat glial cells is restricted to
      oligodendrocytes and carnosine uptake to astrocytes.
AB  - Cultures of glial cells consisting predominantly of oligodendrocytes and
      astrocytes were prepared to study whether the biosynthesis of carnosine (beta-Ala
      His) and the cellular uptake of this dipeptide are processes which are associated
      with a specific cell type. Uptake of the radiolabeled precursor beta-alanine was
      observed in both cultures. Synthesis of radiolabeled carnosine, however, was only
      observed in oligodendrocyte cultures prepared from rat brain and spinal cord.
      During oligodendrocyte cultivation we observed a significant increase in the rate
      of carnosine synthesis which correlates with the differentiation of these cells
      as revealed by immunostaining with antibodies against oligodendrocyte markers.
      Carnosine synthesis was not observed in astroglia cell cultures that were
      depleted of residual O2-A progenitor cells and oligodendrocytes by antibody
      mediated complement cell killing. Contrary to the synthesis, carnosine was found
      to be taken up effectively only by astrocytes but not by oligodendrocytes.

PMID- 8880747
TI  - Remarkable beta-endorphinergic innervation of human cerebral cortex as revealed
      by immunohistochemistry.
AB  - Beta-Endorphin immunoreactivity has been localized in 12 regions of the post
      mortem human cerebral cortex by using a polyclonal antiserum specifically
      recognizing the peptide. Cell bodies and proximal dendrites of certain cortical
      neurons (mostly interneurons) were densely populated with nerve endings
      immunoreactive for beta-endorphin. These 'endorphinoceptive' nerve cells were
      most abundantly present in the cingulate cortex as well as in the Gyri frontales
      superior and medius. In other cortical areas they appeared with much lower
      frequency (Gyri ambiens, semilunaris, parahippocampalis, temporalis). Our data
      show that the human cerebral cortex receives an endorphinergic innervation which
      might be of potential interest with regard to certain neuropsychiatric and
      neurodegenerative disorders.

PMID- 8880748
TI  - Bax protein-like immunoreactivity in primary sensory and hypothalamic neurons of
      adult rats.
AB  - Bax protein-like immunoreactivity (Bax-ir) was examined in the perfusion-fixed,
      cryosectioned rat nervous system. In the central nervous system, hypothalamic
      neurons were the only neurons that exhibited Bax-ir in the cell body. Their axons
      traveled toward the median eminence, suggesting that the Bax-like immunoreactive
      (Bax-ir) hypothalamic neurons included neurosecretory ones. Bax-ir axons were
      observed in the solitary tract nucleus, and spinal and medullary dorsal horns.
      They appear to have been derived from Bax-ir primary sensory neurons in the
      viscerosensory nodose ganglion and somatosensory dorsal root and trigeminal
      ganglia. In the somatosensory ganglia, smaller cells exhibited stronger Bax-ir.
      Accordingly, the ir axons in the dorsal horn were most concentrated in lamina II.

PMID- 8880749
TI  - Freeze-etched neuronal growth cones from rat cerebral cortex at birth: plasma
      membrane morphology in relation to synapse formation.
AB  - Isolated growth cones from the cerebral cortex of newborn rats were studied using
      the freeze-etching technique. The intramembranous structure of their plasma
      membranes was examined in detail and synaptic sites were found. Their membrane
      morphology was compared with that of the synaptic sites in adult animals and
      several differences between them were established. The importance of the present
      results for understanding the formation and development of the synaptic sites in
      the cerebral cortex is outlined.

PMID- 8880750
TI  - Internal consistency of dipole localizations for the human movement-evoked
      magnetic field component 1 (MEF 1).
AB  - The present magnetoencephalographic study was conducted in order to assess the
      accuracy of dipole localizations for the movement-evoked field component 1 (MEF
      1). Three male subjects were requested to perform self-paced flexions of their
      index finger and thumb in repeated sessions of 60 trials while the neuromagnetic
      field was recorded by a 31 channel system. Single moving dipole localizations
      were performed for the MEF 1. The error within single sessions was calculated by
      split-half reliability and window-homogeneity in a total of 61 sessions. The mean
      spatial deviation between both halves amounted to 3.8 mm. The window-homogeneity
      was found to be 2 mm deviation/10 ms.

PMID- 8880751
TI  - Alterations in rat spinal cord cGMP by peripheral nerve injury and adrenal
      medullary transplantation.
AB  - Adrenal medullary chromaffin cells implanted into the spinal subarachnoid space
      can reduce abnormal pain-related responses in chronic pain models. Persistent
      pain is thought to involve the activation of N-methyl-D-aspartate (NMDA)
      receptors and subsequent production of nitric oxide (NO) and cyclic guanosine
      3',5'-monophosphate (cGMP). Changes in dorsal horn levels of cGMP in the rat were
      determined in conjunction with alterations in pain behaviors following peripheral
      nerve injury and adrenal medullary transplantation. Results indicated increased
      spinal cGMP levels in parallel with thermal and mechanical hyperalgesia and
      tactile allodynia consequent to chronic constriction injury of the sciatic nerve
      in rats. Adrenal medullary, but not control transplants, attenuated the
      hyperalgesia and allodynia and decreased spinal cGMP content. These results
      suggest that adrenal medullary transplants may reduce abnormal pain by
      intervention in the spinal NMDA-NO cascade.

PMID- 8880752
TI  - Amphetamine releases dopamine from synaptic vesicles by dual mechanisms.
AB  - Low concentrations of D-amphetamine (AMPH) released [3H]dopamine (DA) from
      purified, rat brain synaptic vesicles with exponential kinetics and a half-time
      of 4 min. Slight alkalinization of the vesicles by AMPH seemed unable to account
      for this release. Instead, it is likely that AMPH partially inhibits DA uptake
      after which DA escapes by an uptake-independent pathway. At high concentrations
      the proton gradient was severely reduced by AMPH and DA was released with a half
      time of < 1 min. Loss of the proton gradient was sufficient to account for this
      DA release. These results show that low concentrations of AMPH release DA from
      synaptic vesicles and suggest that release occurs by different mechanisms at low
      and high AMPH concentrations.

PMID- 8880753
TI  - Acute cocaine results in rapid rises in intracellular free calcium concentration
      in canine cerebral vascular smooth muscle cells: possible relation to etiology of
      stroke.
AB  - Effects of cocaine on intracellular free calcium concentration ([Ca2+]i) in
      cultured canine cerebral vascular smooth muscle cells were studied using digital
      imaging microscopy and the calcium molecular fluorescent indicator, fura-2. Acute
      treatment of cerebral vascular smooth muscle cells with cocaine HCl, from a low
      concentration of 10(-9) M up to 10(-5) M, induced significant increases of
      [Ca2+]i. Irrespective of the changes in [Ca2+]i, the subcellular distribution of
      [Ca2+]i appeared heterogeneous in both normal and cocaine-treated cells. These
      results suggest that cocaine induces cerebral vasospasm by a rapid elevation of
      [Ca2+]i in vascular smooth muscle cells; these ionic events could play a crucial
      role in the pathogenesis of cocaine-induced cerebral ischemia and stroke.

PMID- 8880754
TI  - The intermediate cerebellum may function as a wave-variable processor.
AB  - A newly developed model suggests that the intermediate cerebellum and spinal cord
      gray matter may contribute to movement control by processing control signals as
      wave variables. Within specialized communication systems, wave variables are
      combinations of forward and return signals that ensure stable exchange between
      two sites despite transmission delays. The composition of signals transmitted in
      the ventral spinocerebellar tract appears to be consistent with that of a wave
      variable, and computer simulations of the model yield signals similar to those
      observed in the monkey interpositus nucleus. Wave-variable communication may
      enable the animal motor system to maintain stable, high-performance feedback
      control in the presence of potentially destabilizing signal transmission delays.

PMID- 8880755
TI  - Binding of Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and related peptides to mu 1 and mu
      2 opiate receptors.
AB  - Two endogenous brain peptides (Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and Tyr-MIF-1
      (Tyr-Pro-Leu-Gly-NH2)), a cyclized analog and two fragments of Tyr-W-MIF-1, and
      hemorphin (Tyr-Pro-Trp-Thr) were tested for binding to mu 1 and mu 2 opiate
      receptor. All these peptides bound to both mu 1 and mu 2 sites in assays
      optimized to discriminate these subtypes of the mu opiate receptor in membranes
      from bovine thalamus. The cyclized analog of Tyr-W-MIF-1, previously shown to
      have potency near that of Tyr-D-Ala-Gly-N-MePhe-Gly-ol (DAMGO) and morphine in
      producing analgesia after intracerebroventricular (i.c.v.) injection, bound to mu
      1 and mu 2 sites with affinities similar to those of DAMGO. Tyr-W-MIF-1,
      previously shown to induce analgesia after i.c.v. injection but with much higher
      potency after intrathecal (i.t.) injection, also bound to both mu 1 and mu 2
      sites with an affinity between that of morphiceptin and hemorphin. Although the
      highest ratios of Ki's for mu 2/mu 1 were shown by hemorphin, Tyr-W-MIF-1, and
      Tyr-W-MIF-1, none of the compounds were significantly different in selectivity.
      The results indicate that the relatively lower potency of Tyr-W-MIF-1 after
      i.c.v., compared with i.t. injection, is not due to a lack of binding to mu 1
      sites. They suggest that it has relatively high efficacy at mu 2, but low
      efficacy at mu 1 sites, a possibility that might explain some of the novel
      properties of these peptides.

PMID- 8880756
TI  - The history of spinal biomechanics.
AB  - The history of spinal biomechanics has its origins in antiquity. The Edwin Smith
      surgical papyrus, an Egyptian document written in the 17th century BC, described
      the difference between cervical sprain, fracture, and fracture-dislocation. By
      the time of Hippocrates (4th century BC), physical means such as traction or
      local pressure were being used to correct spinal deformities but the treatments
      were based on only a rudimentary knowledge of spinal biomechanics. The
      Renaissance produced the first serious attempts at understanding spinal
      biomechanics. Leonardo da Vinci (1452-1519) accurately described the anatomy of
      the spine and was perhaps the first to investigate spinal stability. The first
      comprehensive treatise on biomechanics, De Motu Animalium, was published by
      Giovanni Borelli in 1680, and it contained the first analysis of weight bearing
      by the spine. In this regard, Borelli can be considered the "Father of Spinal
      Biomechanics." By the end of the 19th century, the basic biomechanical concepts
      of spinal alignment and immobilization were well entrenched as therapies for
      spinal cord injury. Further anatomic delineation of spinal stability was sparked
      by the anatomic analyses of judicial hangings by Wood-Jones in 1913. By the
      1960s, a two-column model of the spine was proposed by Holdsworth. The modern
      concept of Denis' three-column model of the spine is supported by more
      sophisticated testing of cadaver spines in modern biomechanical laboratories. The
      modern explosion of spinal instrumentation stems from a deeper understanding of
      the load-bearing structures of the spinal column.

PMID- 8880757
TI  - Complications resulting from saphenous vein patch graft after carotid
      endarterectomy.
AB  - OBJECTIVE: Reducing surgical risks to the minimum in carotid endarterectomy has
      become crucial, especially with the results of recent clinical trials extending
      indications to asymptomatic patients. The use of the saphenous vein patch graft
      (SVPG) has been suggested to reduce early postoperative thrombosis and cerebral
      infarct as well as late recurrent stenosis. However, the exact risks and
      complications involved in this technique are not known. METHODS: During a 23-year
      period (1972-1994), 2888 carotid endarterectomies with SVPG for primary carotid
      stenosis were performed by the Neurosurgical Cerebrovascular Service at the Mayo
      Clinic. The data from all patients were retrospectively analyzed, emphasizing
      postoperative complications related to SVPG. RESULTS: There were five
      postoperative vein ruptures (0.17%), four cases of aneurysm formation, and three
      cases of deep infection necessitating surgical intervention. The vein patch
      ruptured in one male patient and four female patients (mean age, 69 yr). All
      ruptures occurred within 4 days of the primary operation, including two during
      the first 24 hours. All patients with rupture underwent emergency surgery and
      were found to have intact suture lines and tears in the middle of the grafts. Two
      patients recovered without deficits, one suffered major disability, and the other
      two died. Aneurysm of the patch developed in two male patients and two female
      patients (mean age, 71 yr). All of the patients developed painless pulsatile neck
      masses 1 to 9 years after the initial surgery; two also had recurrent ischemic
      symptoms. All of the patients with aneurysms underwent surgical correction
      without consequences. CONCLUSION: Although the benefit of routine use of SVPG in
      carotid endarterectomy is still the focus of debate, this analysis showed that
      its use adds a small but definite risk of serious complications related to
      inherent weakness of the venous tissue. If a surgeon chooses to use a patch
      graft, our recommendation is for use of a synthetic material rather than vein.

PMID- 8880758
TI  - Occult cerebrovascular malformations after irradiation.
AB  - OBJECTIVE: It has recently been found that patients receiving cerebral
      irradiation can develop hemorrhagic dysangiogeneses simulating occult vascular
      malformations. To analyze this connection, we report on five patients with occult
      cerebrovascular malformations occurring after "standard" or focused irradiation
      performed for brain tumors in four patients and for a deep-seated cavernous
      angioma in one patient. METHODS: All lesions were within the radiation ports. The
      time interval between irradiation and the detection of the occult vascular
      malformations varied from 3 to 9 years; the ratio of female to male patients was
      4:1. Four patients were < 15 years old when first irradiated. Four patients
      presented with acute symptoms (headache, vomiting, focal signs) and one was
      asymptomatic when the lesions were first detected. Serial magnetic resonance
      imaging scans were available in four patients and a computed tomographic scan in
      the other patient. RESULTS: The initial appearance was that of a hypointense T1
      T2 focus; magnetic resonance imaging then revealed focal or multifocal T1
      hyperintensity and T2 mixed signal intensity followed by a late ring of decreased
      signal intensity. Four patients were operated on and one was under
      neuroradiological monitoring. Histological features of these lesions included
      clusters of closely packed vascular spaces resembling cavernous malformations
      sometimes associated with a thrombosed thick-walled vein with intense hemosiderin
      deposition and fibroblastic proliferation; telangiectasic changes were also seen
      in the adjacent brain. CONCLUSION: Increased awareness of occult cerebrovascular
      malformations is necessary, because their occurrence is not infrequent and they
      have hemorrhagic potential. Children receiving cerebral irradiation are at
      greater risk of this complication.

PMID- 8880759
TI  - Intracranial aneurysms and cervicocephalic arterial dissections associated with
      congenital heart disease.
AB  - OBJECTIVE: The number of patients with congenital heart disease who survive to
      adolescence and adulthood continues to increase. We review our experience with
      noninfectious intracranial aneurysms and cervicocephalic arterial dissections in
      patients with congenital heart disease, expanding the clinical spectrum of the
      cerebrovascular abnormalities that may be encountered in this group of patients.
      METHODS: All patients with congenital heart disease and intracranial aneurysms of
      cervicocephalic arterial dissections, who were evaluated at the Mayo Clinic
      between 1969 and 1992, were identified. RESULTS: Congenital heart disease was
      diagnosed in 3 (8%) of 36 children with intracranial aneurysms, in 5 (0.3%) of
      1994 adults with intracranial aneurysms, in 1 (4%) of 25 children with
      cervicocephalic arterial dissections, and in 5 (2%) of 250 adults with
      cervicocephalic arterial dissections. The mean age of the 14 patients was 32
      years (range, 13-58 yr). The congenital heart disorders consisted of complex
      cardiac anomalies in three patients (truncus arteriosus, transposition of the
      great arteries, and tricuspid atresia in one patient each), pulmonic valve or
      arterial stenosis in two patients, aortic coarctation in four patients, and
      bicuspid aortic valve in five patients. Only one patient had an intracranial
      aneurysm and coarctation of the aorta. CONCLUSION: Individuals with a variety of
      congenital heart disorders may be at an increased risk of intracranial aneurysm
      development and cervicocephalic arterial dissection, particularly in adolescence.
      The muscular arteries of the head and neck are derived from neural crest cells
      and the neural crest is also of major importance in early cardiac development,
      suggesting that an abnormality of the neural crest may be the common pathogenetic
      factor explaining this association.

PMID- 8880760
TI  - The beaten copper cranium: a correlation between intracranial pressure, cranial
      radiographs, and computed tomographic scans in children with craniosynostosis.
AB  - OBJECTIVE: The beaten copper appearance of the cranium, as well as other cranial
      radiographic and computed tomographic findings in children with craniosynostosis,
      is often interpreted by clinicians as evidence of elevated intracranial pressure
      (ICP). However, a correlation between radiological findings and ICP measurements
      has not been previously demonstrated, and their usefulness in detecting elevated
      ICP has not been defined. METHODS: To address those issues, 123 children with
      craniosynostosis who had cranial radiographs and ICP monitoring were studied. To
      assess the specificity of certain radiological findings to patients with
      craniosynostosis, cranial radiographs of patients with craniosynostosis were
      compared to those of age- and sex-matched controls. In patients with
      craniosynostosis, findings on cranial radiographs were compared to computed
      tomographic scans of the brain. Radiographic findings were then correlated with
      ICP measurements obtained while the patient was sleeping, which was measured
      using a Camino fiberoptic ICP monitor (Camino Laboratories, San Diego, CA). All
      radiographs were independently analyzed by two radiologists who were blinded to
      clinical and ICP data. RESULTS: A diffuse beaten copper pattern, erosion of the
      dorsum sellar, and suture diastasis were seen more commonly in patients with
      craniosynostosis than in controls (P < 0.05), but the presence of the beaten
      copper pattern was no more common in children with craniosynostosis. ICP was
      greater when a diffuse beaten copper pattern, dorsum sellar erosion, suture
      diastasis, or narrowing of basal cisterns was present (P < 0.05). CONCLUSION:
      Although this study demonstrates that some cranial radiographic and computed
      tomographic findings do correlate with elevated ICP, the sensitivity of
      radiological methods for detecting elevated ICP is universally low and they are
      not recommended to screen for elevated ICP in children with craniosynostosis.

PMID- 8880762
TI  - Computed tomographic criteria and survival rate for patients with acute subdural
      hematoma.
AB  - OBJECTIVE: Computed tomographic data from 174 patients with acute subdural
      hematoma were analyzed statistically to identify parameters that could be
      evaluated independently of clinical and neurological status to estimate outcome.
      METHODS: This retrospective study was made necessary by the fact that the
      patients admitted usually had been treated with intubation, sedation, and
      artificial ventilation, which precludes neurological examination. RESULTS: In
      surgically treated patients, the hematoma thickness ranged from 5 to 35 mm and
      the midline shift was 0 to 33 mm. In 81 patients (46.6%), the hematoma thickness
      was greater than the midline shift; in 24 patients (13.8%), the hematoma
      thickness equaled the midline shift; and in 69 patients (39.6%), the midline
      shift exceeded the hematoma thickness. Of the patients, 52% died after surgery,
      for 29% we obtained good or satisfying results, and 19% were in poor condition
      after therapy. The Kaplan-Meier survival analysis proved that the survival rate
      was only 50% for a hematoma thickness of approximately 18 mm and a midline shift
      of 20 mm. The survival function dropped markedly for midline shifts of more than
      20 mm and converged to 0% for midline shifts of more than 25 mm. If the midline
      shift exceeded the hematoma thickness by 3 mm, the survival function was 50%;
      when the midline shift exceeded the hematoma thickness by 5 mm, the survival
      function was 25%. The Glasgow Outcome Scale scores were correlated significantly
      with these parameters. The parameters, which are the measured hematoma thickness,
      the midline shift, and the difference between the hematoma thickness and the
      midline shift, allow robust/adequate estimation of survival function and outcome
      for patients suffering from acute subdural hematoma. CONCLUSION: Based on these
      data, indications for surgery could be assessed by means of video conferencing,
      i.e., without personal examination of the patients.

PMID- 8880761
TI  - Pericytosis and edema generation: a unique clinicopathological variant of
      meningioma.
AB  - OBJECTIVE: We report a group of eight patients with a distinctive histological
      variant of meningioma that is associated with severe peritumoral edema. The
      clinical presentation, radiographic findings, and histology of this type of tumor
      may lead to misdiagnosis as an aggressive or malignant process. METHODS: We
      reviewed the histology from patients who had removal of meningiomas performed in
      our institution between 1978 and 1992. Tumors having abnormal proliferation of
      cells in the intramural vascular spaces were selected for study; case histories
      and radiographs were reviewed. Tumor material was subjected to special stains,
      immunocytochemical examination, and election microscopy. RESULTS: Several lesions
      were misread radiographically as being malignant. Patients underwent craniotomy
      with complete excision of the tumor. All lesions were small (< or = 3 cm), and no
      brain invasion, unusual tumor vascularity, or dural sinus involvement was noted
      in any case. Histologically, the meningioma pattern in each case was
      meningothelial and benign in appearance. The immunocytochemical and electron
      microscopic features of the unusual cells in the blood vessel walls are most
      consistent with their being of pericytic origin. All patients have remained
      asymptomatic and without evidence of tumor recurrence with follow-up from 3 to 12
      years. CONCLUSION: These tumors showed proliferation of pericytes in blood vessel
      walls and represent a new subtype of meningothelial meningioma. The apparently
      benign nature of these lesions necessitates their recognition. Characteristic
      findings of pericytic proliferation associated with edema generation have led us
      to descriptively term this the PEG variant of meningioma.

PMID- 8880763
TI  - Early effects of mannitol in patients with head injuries assessed using bedside
      multimodality monitoring.
AB  - OBJECTIVE: We have employed bedside multimodality methods to assess the influence
      of a slow (20 min) bolus of hypertonic mannitol on cerebral hemodynamics in
      comatose patients with head injuries. METHODS: Middle cerebral artery flow
      velocities (FV) and cortical microcirculatory flows were measured in comatose
      patients with head injuries after the administration of 200 ml of 20% mannitol. A
      comparison was made with the effects of an identical bolus of isotonic saline.
      Fourteen patients with diffuse head injuries and with raised intracranial
      pressure were selected, and mannitol infusion studies were conducted when
      clinically indicated (n = 23). Using transcranial doppler and laser doppler
      flowmetry (LDF), indices of estimated cerebrovascular resistance (eCVR) were
      calculated for the macro- (eCVR-FV) and micro- (eCVR-LDF) circulation. RESULTS:
      During mannitol infusion, a significant rise in cerebral perfusion pressure was
      detected (+10%, P = 0.03) as a result of a fall in intracranial pressure (-21%, P
      = 0.001). Increases in both FV (+13%, P < 0.001) and LDF (+14%, P = 0.002)
      occurred only after the administration of mannitol and persisted beyond
      completion of infusion. The effect on FV and LDF decayed exponentially, with a
      time constant of 34.0 and 38.0 minutes, respectively, and was independent of the
      pressure autoregulatory status. There was a tendency for eCVR-FV and eCVR-LDF to
      decrease. No significant effects resulted from the administration of saline.
      CONCLUSION: Bedside multimodality monitoring may provide a useful means for
      assessing the effects of therapy in the comatose patient. The mechanisms by which
      mannitol reduces intracranial pressure in patients with head injuries are
      discussed.

PMID- 8880764
TI  - Hydrocephalus and epilepsy: an actuarial analysis.
AB  - OBJECTIVE: To determine the prevalence of epilepsy among patients with
      hydrocephalus and to identify risk factors. METHODS: Retrospective chart review
      at a single institution was conducted. The definition of epilepsy used was long
      term administration of antiepileptic drugs (AEDs) for suppression of seizures.
      Actuarial methodology was used, with initiation of AED therapy as the endpoint of
      the analysis. RESULTS: Insertion or revision of cerebrospinal fluid (CSF) shunts
      was performed on 464 patients at the study institution from 1976 through 1989. At
      the time of initial CSF shunt insertion, 12% of patients had already been treated
      with AEDs. After the 2nd year, the hazard rate for initiation of AED treatment
      was a constant 2% per year, and by 10 years after initial shunt insertion the
      estimated prevalence of AED treatment had risen to 33%. The cause of the
      hydrocephalus was a strong determinant of the prevalence of AED treatment, but
      most of the statistical effect of the cause was already manifest at the time of
      initial CSF shunt insertion. Age of patient at diagnosis of hydrocephalus, burr
      hole site, number of CSF shunt operations during follow-up, and history of shunt
      infection were factors that had no detectable association with AED treatment.
      CONCLUSION: Epilepsy is common among patients with hydrocephalus, and the risk of
      the development of epilepsy continues indefinitely for those patients. The
      complications of CSF shunt surgery seem to play a relatively minor role in the
      development of epilepsy in this patient population.

PMID- 8880765
TI  - The contralateral transcallosal approach: experience with 32 patients.
AB  - OBJECTIVE: To demonstrate the usefulness of the contralateral transcallosal
      approach for resecting lesions located laterally in or adjacent to the lateral
      ventricle. METHODS: Modifications to the standard ipsilateral transcallosal
      technique include positioning the head with the midline oriented horizontally,
      placing the side with the lesion up, and performing the craniotomy and
      interhemispheric dissection on the contralateral side. This approach avoids a
      transcortical incision, allows gravity to hold open the interhemispheric fissure,
      and increases the lateral exposure of the lesion. This approach was used in 32
      patients with a variety of lesions, including 6 cavernous malformations, 7
      arteriovenous malformations, and 19 tumors of various types. All but three
      lesions were located on the left side. RESULTS: All six cavernous malformations,
      all four benign tumors, and four of the seven arteriovenous malformations were
      resected completely. Malignant tumors were resected subtotally, and three
      arteriovenous malformations required stereotactic radiosurgery to treat residual
      deep nidus. There was no surgical mortality. Two patients experienced
      neurological deterioration. CONCLUSION: The contralateral transcallosal approach
      can be used to treat a variety of lesions safely and successfully.

PMID- 8880766
TI  - Transfacial transclival approach for midline posterior circulation aneurysms.
AB  - OBJECTIVE: To evaluate the use of an anterior, transfacial transclival approach
      to midline posterior circulation aneurysms in five patients. SURGICAL APPROACH: A
      skin incision is made on the right side of the nose with subsequent bony and
      cartilaginous disarticulation of the nasal complex. The nose remains attached
      along the left side and is reflected laterally. Removal of the nasal septum and
      bilateral ethmoidectomy, medial maxillectomy (usually bilateral), and opening of
      the sphenoid yield a large triangular exposure of the anterior clivus. After
      removal of the clivus with a drill, the vertebral and basilar arteries are
      exposed through a midline dural opening. RESULTS: The approach provided excellent
      exposure of basilar artery trunk aneurysms with room available for temporary clip
      placement in three patients. In a fourth patient, a midline posterior inferior
      cerebellar artery aneurysm was clipped using this technique. A basilar trunk
      dissection was treated by proximal basilar occlusion through this exposure in a
      fifth patient. Although three patients developed transient cerebrospinal fluid
      leaks with symptoms of meningitis, no permanent neurological morbidity resulted
      from the use of the approach. CONCLUSION: The transfacial transclival approach to
      midline aneurysms of the basilar trunk and its branches provided excellent
      exposure for surgical treatment in five patients. No patient had postoperative
      palatal dysfunction and cosmetic results were excellent. Cerebrospinal fluid leak
      and meningitis continue to be the major drawbacks to the use of this approach,
      although the availability of modern broad-spectrum antibiotics lessens the chance
      of permanent neurological sequelae.

PMID- 8880767
TI  - Endoscopic closure of postsurgical anterior cranial fossa cerebrospinal fluid
      leaks.
AB  - OBJECTIVE: The primary objective of this study is to present an alternative
      technique to closure of anterior cranial fossa cerebrospinal fluid (CSF) leaks.
      This study also serves to review our experience with our technique and presents
      some technical "tricks" we have learned through experience. METHODS: The design
      of this study is a clinical chart review. The setting is an academic medical
      center. RESULTS: Eight patients were referred for closure of postsurgical CSF
      leaks. Seven of eight patients underwent closure with one attempt and closure was
      achieved after a second attempt in one patient. Follow-up ranged from 1.5 to 4.0
      years. There were no complications. No patient developed an acute or delayed
      episode of meningitis. CONCLUSION: The technique of endoscopic closure of a CSF
      leak is a safe and effective means for closure of a postsurgical anterior cranial
      fossa CSF fistula when performed by an experienced operator.

PMID- 8880768
TI  - Acrylic cranioplasty using miniplate struts.
AB  - OBJECTIVE: Cranioplasty using acrylic is a common procedure in patients with
      cranial defects secondary to trauma, infection, or tumor. The limitations of this
      technique include poor adherence of the acrylic to surrounding bone and
      difficulty in achieving a proper cosmetic contour in complicated cranial defects,
      especially those involving the orbital rim. The authors have been continually
      developing techniques of cranioplasty. METHODS: Ten consecutive cranioplasties
      were performed over the past 5 years using this new technique. TECHNIQUE: The
      authors describe a technique using miniplates as struts to which the acrylic is
      applied using a "reinforced concrete" principle. RESULTS/CONCLUSION: All patients
      achieved excellent cosmetic results with no complications. This technique allows
      contour of the repair site while the acrylic is curing and provides a more
      resilient resulting prosthesis.

PMID- 8880769
TI  - Magnetic resonance neurography of peripheral nerve lesions in the lower
      extremity.
AB  - OBJECTIVE: We describe the clinical application and utility of high-resolution
      magnetic resonance neurography (MRN) techniques to image the normal fascicular
      structure of peripheral nerves and its distortion by mass lesions or trauma in
      the lower extremity. METHODS: MRN images were obtained using a standard 1.5 Tesla
      magnet and custom built phased-array coils. Patients were imaged using T1
      weighted spin echo without and with gadolinium, T2-weighted fast spin echo with
      fat peripheral nerve tumors (three neurofibromas and one schwannoma), two with
      intraneural cysts, and three with traumatic peripheral nerve lesions. Six
      patients with peripheral nerve mass lesions underwent surgery, thereby allowing
      MRN images to be correlated with intraoperative and pathological findings.
      RESULTS: Preoperative MRN accurately imaged the normal fascicular anatomy of
      peripheral nerves and precisely depicted its relation to tumor and cystic
      lesions. Increased signal on T2-weighted fast spin-echo and short tau inversion
      recovery fast spin-echo pulse sequences was seen in the peripheral nerve
      fascicles of patients with clinical and electrodiagnostic evidence of nerve
      injury. CONCLUSION: MRN proved useful in the preoperative evaluation and planning
      of surgery in patients with peripheral nerve lesions.

PMID- 8880770
TI  - Evaluation of hydrocephalic periventricular radiolucency by dynamic computed
      tomography and xenon-computed tomography.
AB  - OBJECTIVE: A common finding of computed tomography in a case of normal-pressure
      hydrocephalus (NPH) is periventricular radiolucency (PVL). We analyzed PVL for
      patients with hydrocephalus, using dynamic computed tomographic and xenon
      computed tomographic techniques to differentiate NPH from similar diseases.
      METHODS: Dynamic computed tomography was evaluated as a method of diagnosing NPH
      in 14 patients with computed tomographic findings of both PVL and ventricular
      dilatation. Of the 14 patients, varying degrees of clinical improvement after
      shunt surgery were observed in 10 (shunt-effective group) but not in the
      remaining 4 (shunt-ineffective group). The difference in arrival time between PVL
      and thalamus, the difference in peak time between PVL and anterior cerebral
      artery, and cerebral blood flow in PVL by xenon-computed tomographic study were
      analyzed. RESULTS: The difference in arrival time between PVL and thalamus was
      significantly longer in the effective group than among the remaining patients.
      There was no significant difference in PVL/cerebral blood flow and the difference
      in peak time between PVL and the anterior cerebral artery between the two groups.
      CONCLUSION: Dynamic computed tomographic analysis of the difference in arrival
      time between PVL and thalamus is useful for diagnosing NPH and predicting
      response to shunting.

PMID- 8880771
TI  - Bovine pericardium for dural grafts: clinical results in 35 patients.
AB  - OBJECTIVE: The United States Food and Drug Administration has recently approved
      the marketing of bovine pericardium as a dural graft material, but literature
      reports of this use are limited. Bovine pericardium has been widely used for
      grafts in cardiac surgery and seems to have suitable properties for use as a
      dural graft. We report the use of glutaraldehyde-processed bovine pericardium for
      dural grafts in 35 patients undergoing cranial and craniospinal operations with
      the objective of providing a clinical assessment of this material and technique.
      METHODS: This report is a retrospective analysis of 35 patients. All available
      records were reviewed and information regarding the indication for grafting,
      graft size, complications, and outcome were collected and analyzed for all
      patients. RESULTS: Indications for grafting included meningioma resection,
      posterior fossa craniotomy, Chiari decompression, dural-based metastases, and
      trauma. Outcomes were good or excellent in 32 patients; the three fair or poor
      outcomes were not related to surgical closure. In no patient was the dural graft
      a significant factor in outcome. Bovine pericardium was found to be easily
      sutured to be watertight using standard suture material. The material is
      relatively inexpensive and requires no additional incision. It has low
      antigenicity and toxicity, good strength, and minimal elasticity. CONCLUSION: In
      this clinical assessment, bovine pericardium was found to be an excellent dural
      graft material.

PMID- 8880772
TI  - Surgical anatomy of the anterior cervical spine: the disc space, vertebral
      artery, and associated bony structures.
AB  - OBJECTIVE: To elucidate the relationships between the neurovascular structures
      and surrounding bone, which are hidden from the surgeon by soft tissue, and to
      aid in avoiding nerve root and vertebral artery injury in anterior cervical spine
      surgery. METHODS: Using six cadaveric spines, we measured important landmarks on
      the anterior surface of the spine, the bony housing protecting the neurovascular
      structures in the lateral disc space, and the changes that occur during the
      discectomy with interbody distraction of the vertebral bodies. The measurements
      included the distance between the medial borders of the longus colli muscle at
      the level of each interspace; the width and height of each disc space at the
      midline; the width and height of the costal process; the distances between the
      cranial tip of the uncinate process (UP) and the vertebral body (VB) above and
      from the tip of the UP to the vertebral artery; the anteroposterior diameter or
      the extent of the disc spaces in the midline; the height at the midpoint of the
      distracted disc space; the UP-VB distance in distraction; and the width of the
      visible nerve root. RESULTS: The distance between the medial borders of the
      longus colli muscles increased in a rostral to caudal direction. The height of
      the UP was shortest at C4-C5 and greatest at C5-C6; the width was narrowest at C4
      C5 and widest at C6-C7. The width of the costal process measured from the VB to
      the anterior tubercle was narrowest at C2-C3 and widest at C6-C7. The midpoint
      height of the costal process was smallest at C6-C7 and tallest at C4-C5 and C5
      C6. The nondistracted UP-vertebral artery distance was the shortest at C2-C3 and
      longest at C4-C5. The nondistracted UP-VB distance averaged 1 mm at C2-C3 and C6
      C7 and 1.5 mm at C4-C5. The height of the distracted disc space was shortest at
      C2-C3 and C6-C7. The UP-VB distance after distraction was greatest at C4-C5. Only
      at the C2-C3 interspace was the nerve always above the process. The vertebral
      artery entered the foramen transversarium of C6 in all the specimens. CONCLUSION:
      Although avoiding unfortunate injury is not always possible, understanding the
      locations and relations among the anatomic features is the only safeguard against
      unwarranted damage.

PMID- 8880773
TI  - Microsurgical anatomy of the infratemporal fossa as viewed laterally and
      superiorly.
AB  - OBJECTIVE: Benign tumors involving cavernous sinus, trigeminal nerve, and middle
      cranial fossa occasionally extend to the infratemporal fossa (ITF). In this
      study, we describe the microsurgical anatomy and dissection of the ITF, as viewed
      laterally and superiorly. We also describe a new bypass graft to the supraclinoid
      internal carotid artery using the internal maxillary artery (IMA), which is found
      in the ITF. METHODS: Twelve cadaver specimens were used. Dissection required
      zygomatic arch osteotomy, downward displacement of the temporalis muscle,
      extensive subtemporal craniectomy, and mild elevation of the temporal lobe
      together with the dura. RESULTS: The anatomic relationships between the lateral
      and medial pterygoid muscles and the neurovascular bundle of the ITF are
      demonstrated. The neurovascular bundle contains the IMA, which runs horizontally,
      and the main branches of the mandibular nerve, which run vertically. The course
      and anatomic variations of the IMA and inferior alveolar, lingual,
      auriculotemporal, and buccal nerves are shown. The distal IMA was quite tortuous
      and, when the artery straightened, we were able to perform a tension-free in situ
      IMA graft to the supraclinoid carotid artery in 9 of 12 specimens. CONCLUSIONS:
      Knowledge of the anatomy of the ITF is a prerequisite for tumor resection in this
      area. The IMA may serve as a bypass graft to the supraclinoid internal carotid
      artery if the cavernous or petrous carotid artery is involved by tumor and needs
      to be sacrificed.

PMID- 8880774
TI  - Functional anatomic relationship between brain-stem tumors and cranial motor
      nuclei.
AB  - OBJECTIVE: To identify patterns of cranial motor nuclei (CMN) displacement in
      cases of intramedullary brain stem tumor, using neurophysiological mapping of
      motor nuclei on the floor of the fourth ventricle. METHODS: Relationships between
      tumors and CMN were reviewed in 18 patients with brain stem tumors (seven
      pontine, nine medullary, and two pontomedullary tumors) and 2 with
      cervicomedullary junction spinal cord tumors. CMN VII, IX/X, and XII were mapped
      by applying electrical stimuli over the surgically exposed fourth ventricular
      floor through a handheld probe and recording electrical activity in the
      appropriate cranial muscles. RESULTS: Tumors distorted the anatomic location of
      CMN in repetitive patterns according to tumor site. Three patterns were
      identified as follows: Type 1, CMN located around the tumor on the floor of
      fourth ventricle; Type 2, one or more CMN located ventrally to the tumor; Type 3,
      CMN in original anatomic position. Six of seven patients with pontine tumors
      showed the Type 1 pattern. Seven of nine patients with medullary tumors showed
      Type 2, and the other two showed Type 1. Both patients with pontomedullary tumors
      showed Type 2. One patient with a cervicomedullary junction spinal cord tumor
      showed Type 1 and the other Type 3, depending on the tumor extension into the
      fourth ventricle. CONCLUSION: Pontine tumors push the CMN to around the tumor
      edge, suggesting that precise localization of CMN before tumor resection is
      necessary to avoid their damage. Medullary tumors grow more exophytically and
      compress the CMN ventrally. Understanding patterns of CMN displacement can help
      surgeons establish the surgical plan, minimize risks, and enable safer surgery of
      brain stem tumors.

PMID- 8880775
TI  - Response of spinal cord blood flow to the nitric oxide inhibitor nitroarginine.
AB  - OBJECTIVE: The extent to which nitric oxide (NO) is involved in the modulation of
      spinal cord blood flow (SCBF) in the uninjured and injured cord is unknown. To
      elucidate these questions, the following experiments in anesthetized rats were
      conducted. METHODS: Because NO is an unstable free radical with a half-life of
      seconds, its role can be understood through the study of the NO synthase
      inhibitor L-NG-nitroarginine (L-NOARG). L-NOARG was administered intravenously
      for 30 minutes at a dose of 100 or 500 micrograms/kg/min in 12 and 10 uninjured
      animals, respectively. SCBF fluctuations at C7-T1 were measured using laser
      doppler flowmetry. In a second set of 12 rats, L-NOARG (500 micrograms/kg/min)
      was administered 10 minutes before spinal cord injury using a modified aneurysm
      clip at C7-T1 and continued for 30 minutes thereafter. RESULTS: In the uninjured
      animals, L-NOARG was associated with a dose-dependent increase in mean arterial
      pressure of 20 to 80% above baseline (P = 0.0001), together with a dose-related
      decrease in SCBF (P = 0.0373). In the injured animals, L-NOARG was associated
      with a 48% increase in mean arterial pressure. With L-NOARG, the changes in SCBF
      from baseline after injury were similar to those of noninjured controls (n = 25)
      and significantly less than injury controls (n = 18) or those receiving
      phenylephrine (n = 8). CONCLUSION: NO synthase inhibitors, by reducing available
      NO, cause systemic vasoconstriction and a decrease in SCBF in the uninjured
      spinal cord. In the injured spinal cord, the administration of L-NOARG results in
      a redistribution of blood flow with an augmentation in posttraumatic SCBF at the
      injury site.

PMID- 8880776
TI  - Ultrastructural evidence for arteriolar vasospasm after spinal cord trauma.
AB  - OBJECTIVE: The primary objective of this study was to investigate the potential
      contribution of vasospasm to the cascade of secondary injury process after
      traumatic spinal cord injury. Although ischemic factors have been implicated, in
      that vessel rupture, compression, and intravascular thrombosis are readily
      identifiable, vasospasm has been more difficult to detect. METHODS: The sulcal
      arterioles in the ventral median fissure of the cervical spinal cord from adult
      rats were quantitatively examined at the ultrastructural level up to 24 hours
      after compression injury. RESULTS: There were statistically significant changes
      in the luminal cross-sectional area of sulcal arterioles after spinal cord
      injury, correlating directly with decreases in length and increases in width of
      medial smooth muscle cells. A simple mathematical model of postinjury blood flow
      is presented, suggesting an 80% decrease caused by vasospasm alone. CONCLUSION:
      Our results clearly implicate vasospasm as a contributing factor to secondary
      injury processes after traumatic spinal cord injury.

PMID- 8880777
TI  - Effect of P2-purinoceptor antagonists on hemolysate-induced and adenosine 5'
      triphosphate-induced contractions of dog basilar artery in vitro.
AB  - OBJECTIVE: To test the hypothesis that the vasoactive effects of hemolysate of
      dog erythrocytes on dog basilar artery in vitro are caused by adenosine 5'
      triphosphate (ATP). METHODS: Dog erythrocyte hemolysate was assayed for ATP by
      high-pressure liquid chromatography. Dog basilar arteries were cut into rings and
      studied under isometric tension to determine the effects of the P2-purinoceptor
      antagonists suramin, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, and
      reactive blue 2 on contractions induced by hemolysate, prostaglandin F2 alpha
      (PGF2 alpha), KCl, uridine 5'-triphosphate, and ATP. RESULTS: Dog erythrocyte
      hemolysate contained 34 mumol/L of ATP. Hemolysate produced concentration
      dependent contractions of dog basilar artery. Suramin (100 mumol/L) significantly
      inhibited contractions to hemolysate, ATP, and uridine 5'-triphosphate but not to
      PGF2 alpha and KCl (P < 0.05). Pyridoxal phosphate-6-azophenyl-2',4'-disulfonic
      acid (100 mumol/L) caused a small but significant reduction of the contractions
      to hemolysate and did not affect contractions to PGF2 alpha and KCl. Reactive
      blue 2 (30 mumol/L) produced significant inhibition of contractions to hemolysate
      and PGF2 alpha but did not affect contractions to KCl. CONCLUSION: These findings
      suggest that ATP mediates a smooth muscle contractile response of hemolysate on
      dog basilar artery. Because erythrocyte cytosol is known to be important in the
      pathogenesis of vasospasm, these results suggest that ATP may contribute to the
      vasoconstriction that occurs in vasospasm.

PMID- 8880778
TI  - Enzyme-linked immunosorbent assay quantification of cytokine concentrations in
      human meningiomas.
AB  - OBJECTIVE: To gain insight into the network of cytokine gene expression in the
      brain tumor microenvironment, we investigated the presence of the following
      cytokines in freshly excised brain tumors: interleukin (IL)-1 beta, IL-2, IL-4,
      and IL-6. METHODS: Tumor specimens from nine meningiomas were grown as tissue
      explants. The supernatants from the explants were tested for the presence of the
      aforementioned cytokines via the enzyme-linked immunosorbent assay method.
      RESULTS: IL-6, which is thought to stimulate acute protein phase synthesis,
      neovascularization, and cell proliferation, was found in all of the samples in
      greater concentrations than the other cytokines tested. IL-1 beta, another
      stimulatory cytokine thought to be involved in acute protein phase synthesis and
      cell proliferation, was also found in 100% of the samples tested, in
      concentrations significantly lower than those of IL-6. As expected, the presence
      of IL-2 and IL-4 was not detectable in any of the samples. CONCLUSION: This study
      is the first to clearly determine the relative concentrations of IL-1 beta and IL
      6, using enzyme-linked immunosorbent assay quantification. These findings are an
      important precursor to future studies using antibodies to IL-1 beta and IL-6 and
      antibodies to IL-6 receptors to modulate neoplastic growth both in vitro and in
      vivo.

PMID- 8880779
TI  - Neurosurgery at the Montreal Neurological Institute and McGill University
      Hospitals.
AB  - For the past 60 years, the Montreal Neurological Institute and Hospital and three
      associated McGill University teaching hospitals have provided a broad course of
      instruction in neurosurgery and the related neurosciences. This integrated
      program offers a wealth of experience in adult and pediatric neurosurgery, based
      on a total of 140 beds, covering a full range of general and subspecialty
      neurosurgery. The institute, recognized for many years as a world center for
      epilepsy surgery, has traditional strengths in the treatment of brain tumors and
      cerebrovascular and spinal disorders; it has been at the cutting edge of brain
      imaging in all modalities applied to neurosurgical diagnosis and cerebral
      localization, including three-dimensional monitoring in the operating room. New
      approaches to stereotactic procedures have been developed in conjunction with
      imaging technology, including functional neurosurgery and the versatile McGill
      double rotation method for radiosurgery with a linear accelerator. Experience in
      managing trauma, pediatric cases, and general neurosurgical problems is gained at
      the Montreal General Hospital, the Montreal Children's Hospital, and the Jewish
      General Hospital. Well-established research units, including burgeoning groups in
      neurogenetics, molecular neurobiology, and neural regeneration, provide a wide
      variety of academic opportunities to provide trainees with a sound basis for
      coping with the rapidly advancing field of neurosurgery.

PMID- 8880780
TI  - Contralateral cerebellar hemorrhagic infarction after pterional craniotomy:
      report of five cases and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Five cases of cerebellar hemorrhagic infarction
      complicating pterional craniotomy are presented. Recognition of this rare
      complication may be delayed, with catastrophic consequences, because clinicians
      are unaware of the possibility. We suggest that the mechanism of this
      complication is dislocation of the dependent part of the cerebellum and venous
      obstruction causing hemorrhagic infarction. CLINICAL PRESENTATION: Five patients
      undergoing pterional craniotomies for benign conditions (four unruptured
      aneurysms and one meningioma) developed hemorrhagic infarction of the
      contralateral cerebellum in the postoperative period. This resulted in
      obstructive hydrocephalus and brain stem compression. A review of the literature
      revealed only one previous report of a similar complication in patients with
      gross coagulopathy. This was not a problem in our patients. INTERVENTION: The
      time of onset of symptoms varied from immediately postoperative to 24 hours
      later. Once the diagnosis was made, the hydrocephalus was drained and the
      posterior fossa was decompressed. CONCLUSION: The outcome depended on two
      variables: 1) the rate of development of hemorrhagic infarction and the
      associated complications and 2) the amount of time that elapsed before remedial
      action was taken. Two patients with the first signs of deterioration in the
      immediate postoperative period had the worst outcome; one died and the other
      remained severely disabled. In two patients with good neurological recovery,
      problems were identified and corrected within 4 hours of the first sign of
      deterioration. Rapid overdrainage of cerebrospinal fluid during supratentorial
      surgery should be avoided, and the fluid volume should be replaced before
      closure. Postoperative evaluation of patients whose conditions deteriorate after
      supratentorial craniotomy should include adequate imaging studies of the
      posterior fossa.

PMID- 8880781
TI  - Direct carotid cavernous fistula after trigeminal balloon microcompression
      gangliolysis: case report.
AB  - OBJECTIVE AND IMPORTANCE: Percutaneous gangliolysis procedures may rarely be
      associated with vascular complications. There are three reported cases of carotid
      cavernous fistulas occurring after percutaneous microcompressive trigeminal
      gangliolysis. This is the only reported case of this complication associated with
      microcompression gangliolysis. CLINICAL PRESENTATION: A 78-year-old woman was
      referred to our institution with a history of abrupt onset of left-sided bruit,
      proptosis, chemosis, and diplopia after a percutaneous retrogasserian
      microcompression. INTERVENTION: Cerebral angiography revealed a large left direct
      carotid cavernous fistula. Attempts at balloon embolization were unsuccessful,
      and the lesion was ultimately cured by transarterial and transvenous coil
      embolization. CONCLUSION: Follow-up examination revealed no evidence of bruit or
      neurological deficit. This report highlights a unique complication of balloon
      gangliolysis and describes coil embolization of the fistula as the mode of
      treatment.

PMID- 8880782
TI  - Unusual complications at iliac crest bone graft donor site: experience with two
      cases.
AB  - OBJECTIVE AND IMPORTANCE: Two cases of fracture of the iliac crest after graft
      harvesting are presented. Only six such cases have been reported in the
      literature, although more than 100,000 such procedures are performed each year in
      the United States alone. This complication adds to the morbidity of the procedure
      for which the graft is taken. Its avoidance by an appropriate harvesting
      technique will reduce patient disability and shorten hospital stay. CLINICAL
      PRESENTATION: A 56-year-old man who worked as a mechanic underwent anterior
      cervical discectomies and fusion at C5-C6 and C6-C7 for spondylotic
      radiculopathies. Another patient, a 48-year-old man, required mandibular
      reconstruction for squamous cell carcinoma. Both grafts were harvested from the
      iliac crest using osteotomies. On the 9th and 3rd postoperative days,
      respectively, each patient developed groin pain while walking, associated with
      marked tenderness over the graft donor sites. X-rays showed fractured iliac
      crests. INTERVENTION: Apart from bed rest for pain, no specific treatment was
      required. CONCLUSION: The use of the osteotome weakens the iliac crest, leading
      to stress fractures caused by the pulling action of the attached muscles. To
      prevent this from happening, we recommend the use of the oscillating saw, leaving
      a 3-cm spike of iliac crest anteriorly. Nevertheless, this complication has a
      good long-term outcome.

PMID- 8880783
TI  - Symptomatic hypertrophic pacchionian granulation mimicking bone tumor: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Osteolytic lesions can be seen in various diseases, and
      they also resemble the markings normally found on the cranium. We present a rare
      case of symptomatic hypertrophic pacchionian granulation mimicking bone tumor in
      the calvaria. CLINICAL PRESENTATION: A 46-year-old woman suffered from a small
      hump accompanied by pain in the right frontoparietal region. A plain radiograph
      revealed two punched-out lesions. Precontrast-enhanced computed tomographic scans
      demonstrated hypodense masses, with partial defect of the outer table of the
      cranium. Magnetic resonance imaging demonstrated hypointense masses in the T1
      weighted image and hyperintense masses in the T2-weighted image, with capsule
      like contrast enhancement by gadolinium diethylenetriamine penta-acetic acid.
      INTERVENTION: The masses were totally resected with attached bone and dura. One
      of them had destroyed the outer table of the cranium. The affected portions of
      the masses lacked the dura and partially adhered to the brain surface.
      Histologically, hypertrophic pacchionian granulation was diagnosed. CONCLUSION:
      The patient has had no recurrence for 2 years. This case suggests the need to
      include hypertrophic pacchionian granulation in the differential diagnosis of
      punched-out lesions.

PMID- 8880784
TI  - Cervical-to-petrous internal carotid artery saphenous vein in situ bypass for the
      treatment of a high cervical dissecting aneurysm: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe a novel cervical-to-petrous internal
      carotid artery (ICA) saphenous vein in situ bypass for the treatment of a high
      cervical dissecting aneurysm. The cervical ICA has no major collateral branches
      and can be used as a tunnel for the vein graft. CLINICAL PRESENTATIONS: A 25-year
      old man was involved in a car accident. A cerebral angiogram revealed a right ICA
      dissection with aneurysm formation at the C1-C2 level. The patient recovered
      fully and was anticoagulated. Six months after the initial angiogram, a second
      angiogram disclosed ICA stenosis (80%) and persistence of the traumatic
      dissecting aneurysm. Definitive surgical bypass was considered the most
      appropriate course of action. TECHNIQUE: The horizontal portion of the petrous
      ICA was exposed by an extradural subtemporal approach. The cervical arteries were
      exposed by a separate surgical incision. After dividing the petrous ICA and the
      cervical ICA, the cervical ICA was dilated using a Fogarty balloon embolectomy
      catheter. A saphenous vein graft was inserted inside the lumen of the cervical
      ICA and was anastomosed to the ICA end-to-end both proximally and distally
      (cervical-to-petrous ICA in situ bypass). The graft was patent on the follow-up
      angiogram. CONCLUSION: We describe a new technique that could be considered an
      alternative to the classical extra-anatomic cervical-to-petrous ICA bypass
      procedures.

PMID- 8880785
TI  - Surgical needle design: torsion resistance.
AB  - OBJECTIVE: The interface between a surgical needle and forceps affects needle
      forceps stability. Stability has become more important with the introduction of
      blunt-point surgical needles. The stability at the needle-forceps interface can
      be assessed by quantitating resistance to both rotation and twisting. Two
      commonly used surgical needles are the MO and CT needles, which are particularly
      useful for soft tissue closure for which significant strength of closure is
      required. Their comparison is thus of importance to surgeons. The design of the
      MO needle (greater flat section width than the CT needle) should allow for a
      greater resistance to rotation at the needle-forceps junction. This theoretically
      makes the MO needle a better choice when blunt-point needles (which require a
      greater force to penetrate tissue) are used. The objective of this study is to
      document and quantitate the differences, if any, between the CT and MO needles
      with regard to rotation and twisting at the needle-forceps junction. METHODS: To
      compare the efficacy of the CT and MO needles with regard to needle-forceps
      stability, the resistance of the needles to rotation and twisting was assessed
      using a Hios HP-10 digital torque meter. RESULTS: The resistance to twisting of
      the CT and MO needles was not significantly different. However, the MO needle is
      25% more resistant to rotation than the CT needle. This differed by 10% from the
      expected difference. CONCLUSION: The resistance to twisting is not significantly
      affected by needle geometry, whereas the resistance to rotation is significantly
      affected. The difference between expected and observed differences in rotation is
      explained by study design.

PMID- 8880786
TI  - Crush injuries to the head.

PMID- 8880787
TI  - Hypoxia-mediated selection of cells with diminished apoptotic potential to solid
      tumours.

PMID- 8880788
TI  - Intramedullary subependymoma of the spinal cord.

PMID- 8880789
TI  - Pallidotomy: a survey of current practice in North America.
AB  - Twenty-eight centers completed a survey about their current practice of
      pallidotomy. This sample represents a non-exhaustive survey of the current
      practice of pallidotomy in North America and is not a study of outcomes. 1015
      patients underwent 1219 pallidotomies: 811 (80%) unilateral, 72 (7%) staged
      bilateral, and 132 (13%) simultaneous bilateral. Pallidotomy has long been an
      accepted procedure and the indications for this surgery, in the opinion of the
      responding centers, were rated on a scale of 1 (poor) to 4 (excellent) and
      demonstrated dyskinesia as the best indication (median = 4); on-off fluctuations,
      dystonia, rigidity, and bradykinesia as good indications (median = 3); and
      freezing, tremor and gait disturbance as fair indications (median = 2). Most
      centers used MRI alone (50%) or in combination with CT scan (n = 6) or
      ventriculopathy (n = 5) to localize the target. The median values of pallidal
      coordinates were: 2 mm anterior to the midcommissural point 21 mm lateral to the
      midsagittal plane and 5 mm below the intercommissural line. Microrecording was
      performed by half of the centers (n = 14) and half of the remaining centers were
      considering starting it (n = 7). Main criteria used to define the target included
      the firing pattern of spontaneous neuronal discharges (n = 13) and the response
      to joint movement (n = 10). Most centers performed motor (n = 26) and visual (n =
      23) macrostimulation. Twenty four centers performed test lesions using median
      values of 55 degrees C temperatures for 30 s. Final lesions consisted of 3
      permanent lesions placed 2 mm apart, each lesion created with median values of 75
      degrees C temperatures for 1 minute. Median hospital stay was 2 days.

PMID- 8880790
TI  - Implantable transvenous cardioverter defibrillator leads: the dark side.

PMID- 8880791
TI  - The effect of ventricular activation sequence on cardiac performance during
      pacing.
AB  - The aim of this study was to evaluate the importance of a normal ventricular
      activation pattern for cardiac performance. In nine mongrel dogs, atrial pacing
      was compared to AV synchronous pacing at three different AV delays (150, 100, and
      60 ms). In six dogs, proximal septal AV synchronous pacing was compared to apical
      AV synchronous pacing at three different AV delays. AV synchronous pacing was
      performed after RF induced complete heart block. Hemodynamics were evaluated by
      assessment of positive and negative dP/dt, cardiac output, and left ventricular
      and pulmonary pressures. Atrial pacing was superior to AV synchronous pacing with
      respect to positive and negative dP/dt and cardiac output. This difference was
      present at all AV delays. Proximal septal pacing was associated with a higher
      positive and negative dP/dt compared to apical pacing at all AV delays. Left
      ventricular activation time was significantly shorter during proximal septal
      pacing than during apical pacing (88 +/- 4 vs 115 +/- 4 ms, P < 0.001). We
      conclude that atrial and proximal septal pacing improves cardiac function and
      shortens the ventricular activation time compared to apical AV synchronous pacing
      independent of the AV interval.

PMID- 8880792
TI  - Acute effects of radiofrequency ablation of atrial arrhythmias on implanted
      permanent pacing systems.
AB  - We studied the safety of performing RF catheter ablation in patients with
      implanted permanent pacemakers by monitoring the function of implanted pacing
      systems before, during, and immediately after exposure to RF energy. Patients
      with implanted pacing systems may require RF ablation for treatment of a variety
      of tachyarrhythmias. High frequency electromagnetic fields, such as RF energy,
      may affect implanted pacing systems, causing temporary or permanent loss of
      output, undersensing, oversensing, asynchronous pacing, or reversion to "reset"
      (Recommended Replacement Time or Power On Reset) parameters. Thirty-five patients
      with implanted pacing systems (23 DDDR, 6 VVIR, 5 DDD, 1 VVI, 31 bipolar and 4
      unipolar) underwent RF catheter ablation. Prior to ablation, each pacing system
      underwent measurements of pacing and sensing thresholds, telemetry of
      intracardiac electrograms and measurement of battery voltage and lead
      impedance(s). During ablation, pacemaker function was monitored by real-time
      telemetry, intracardiac electrograms, and surface ECG. Immediately after
      ablation, each pacing system was reevaluated. Telemetry during RF ablation
      revealed normal pacing and sensing in 14 (40%) of 35 patients. Refractory period
      extension with asynchronous pacing and noise mode reversion were seen in 16 (46%)
      of 35 patients. Rare under- and/or oversensing, reversion to reset parameters,
      and telemetry "lock up" with inhibition of pacing output was seen in a few
      patients. After ablation, there were no significant changes in atrial or
      ventricular pacing or sensing thresholds or measurements of atrial and
      ventricular lead impedances. We conclude that most permanent pacemakers are not
      adversely affected by exposure to RF energy during catheter ablation. A variety
      of pacemaker behaviors may be seen during RF ablation, and a thorough
      understanding of each pulse generator's potential response(s) to electromagnetic
      interference is important before undertaking catheter ablation in patients with
      permanent pacemakers. Careful reevaluation of the patient's pacing system
      following the procedure is mandatory.

PMID- 8880793
TI  - Difference in QT interval measurement on ambulatory ECG compared with standard
      ECG.
AB  - Measurement of the QT interval on standard ECG has diagnostic importance in the
      congenital long QT syndrome, in pharmacological therapy of arrhythmias, as well
      as in ischemic heart disease. It has been suggested that QT prolongation on
      ambulatory ECG (Holter) may have similar importance. To assess agreement between
      methods, QT interval measurement on standard ECG was compared to that on Holter.
      Simultaneously obtained ECG and Holter tracings (25 mm/s) of the same complexes
      in leads V1 and V5 were studied in 14 patients (age range 4-36 years). ECG pairs
      (n = 100, 49 V1 and 51 V5) were compared over a range of QT interval from 300-620
      ms, as determined with the use of calipers by two observers blinded to pairing
      relationship. Correlation between methods was high for both observers (observer
      1:r[V1] = 0.872, r[V5] = 0.973; observer 2: r[V1] = 0.972, r[V5] = 0.988), and
      interobserver variability was small (> 85% of measurements within 20 ms). As
      compared to ECG, Holter underestimated QT interval in V1, mean difference (QT
      [Holter]-QT [ECG]) observer 1 (-23 ms, P < 0.001), observer 2 (-7 ms, P < 0.05),
      and overestimated QT in V5, mean difference observer 1 (+13 ms, P < 0.001),
      observer 2 (+ 13 ms, P < 0.001). However, individual variation between methods
      was wide, as expressed by the difference between individual measurements (95%
      confidence interval [V1]: observer 1 [-99 to +53 ms] observer 2 [-47 to +33 ms];
      [V5]: observer 1 [-33 to +59 ms] observer 2 [-17 to +43 ms]). Furthermore, when
      using the QTA (interval from onset of Q wave to apex of T wave) similar
      variability was observed. In the assessment of QT interval, potential sources of
      error of this magnitude could limit the clinical utility of ambulatory monitoring
      in detecting prolongation of the QT interval for diagnostic purposes.

PMID- 8880794
TI  - Diaphragm pacing with a quadripolar phrenic nerve electrode: an international
      study.
AB  - We sought to determine the international experience with the quadripolar
      diaphragm pacer system and to test two hypotheses: the incidence of pacer
      complications would be (1) increased among pediatric as compared to adult
      patients; and (2) highest among active pediatric patients with idiopathic
      congenital central hypoventilation syndrome (CCHS). Data were collected via a
      questionnaire coupled with the Atrotech Registry data for a total of 64 patients
      (35 children and 29 adults) from 14 countries. Thoracic implantation of
      electrodes and bilateral pacer use each occurred in 94% of all subjects.
      Tetraplegic (vs pediatric CCHS) patients were more typically paced 24 hours/day
      (P = 0.001). Pacing duration averaged 2.0 +/- 1.0 years among children and 2.2 +/
      1.1 years among adults. Infections occurred among 2.9% of surgical procedures,
      all in pediatric CCHS patients (vs pediatric tetraplegic patients, P = 0.01). The
      incidence of mechanical trauma was 3.8%, without significant differences among
      patient groups. The incidence of presumed electrode and receiver failure were
      3.1% and 5.9%, respectively, with internal component failure greater among
      pediatric CCHS than pediatric tetraplegic patients (P < 0.01). Intermittent or
      absent function of 0-4 electrode combinations occurred among 19% of all patients,
      with increased frequency among pediatric CCHS than pediatric tetraplegic patients
      (P < 0.03). Complication-free successful pacing occurred in 60% of pediatric and
      52% of adult patients. In all, 94% of the pediatric and 86% of the adult patients
      paced successfully after the necessary intervention. Although pacer complications
      were not increased among pediatric as compared to adult patients, the incidence
      of complications was highest among the active pediatric patients with CCHS.
      Longitudinal study of these patients will provide invaluable information for
      modification and improvement of the quadripolar system.

PMID- 8880796
TI  - Appraisal of pacing lead performance from the Danish Pacemaker Register.
AB  - The Danish Pacemaker Register was established in January 1982, and the 11
      implanting centers in Denmark report to the Register on a continuous basis by use
      of the European Pacemaker Patient Identification Card proposed by the European
      Working Group on Cardiac Pacing. As of May 1994, the Register contained data on
      18,053 lead implants performed in Denmark, i.e., 1,253 (7%) lead implants before
      1982, and all the 16,800 initial lead implants since 1982 on 17,020 generators in
      15,366 patients for a total of 12,188 (67.5%) ventricular unipolar, 3,178 (17.6%)
      ventricular bipolar, 1,316 (7.3%) atrial unipolar, and 1,371 (7.6%) atrial
      bipolar leads. Preformed J shaped leads were used in 3.5% of the atrial implants
      and active fixation in < 8%. Lead failure was defined as need for replacement or
      abandonment of the lead due to pacing or sensing problems with the exception of
      lead displacement. The 10-year survival rate for unipolar atrial and ventricular
      leads was 95.8% +/- 2.1% (2 standard errors) and 97.1% +/- 0.6%, respectively, as
      compared to a 4-year survival rate of 91.5% +/- 4.6% and 91.6% +/- 1.7% for
      bipolar atrial and ventricular leads, and an 8-year survival rate for bipolar
      ventricular leads of 75.1% +/- 5.0%. The 5-year survival rate for the bipolar
      Medtronic model 4012 lead was 85.8% +/- 8.1% and 67.4% +/- 7.3% for the bipolar
      Siemens model 1010T lead, indicating a poor performance. The Siemens lead models
      105T and 1050T seem to be performing like the model 1010T. The 5-year survival
      rate for the bipolar Telectronics model 284 lead was 88.4% +/- 6.2%. The data
      from the Danish Pacemaker Register confirm the previous reported good survival of
      unipolar pacing leads irrespective of the chamber paced, and demonstrate that the
      bipolar Medtronic 4012 lead, the bipolar Telectronics 284 lead, and especially
      the bipolar Siemens 1010T, 105T, and 1050T models are unreliable leads that need
      careful monitoring and appropriate replacement.

PMID- 8880795
TI  - A randomized, single-blind crossover comparison of the effects of chronic DDD and
      dual sensor VVIR pacing mode on quality-of-life and cardiopulmonary performance
      in complete heart block.
AB  - The aim of this study was to compare DDD and dual sensor VVIR (activity and QT)
      pacing modes in complete AV block (CAVB). Eighteen patients (14 men and 4 women,
      aged 70 +/- 6.5 years) implanted with a dual chamber, dual sensor pacemaker for
      CAVB with normal sinus node chronotropic function were studied. A quality-of-life
      and cardiovascular symptom questionnaire, and a treadmill exercise test were
      completed after a period of VVIR and a period of DDD pacing, each lasting 1
      month. Overall quality-of-life and cardiovascular symptoms did not significantly
      differ, though three patients felt discomfort during VVIR mode. There was no
      significant statistical difference in cardiopulmonary parameters. DDD and VVIR
      modes yielded the following respective data: maximum heart rate = 105.7 +/- 21.8
      beats/minute versus 107.6 +/- 21.6 beats/minute (NS); maximum workload = 60 +/-
      33.4 W versus 59.3 +/- 37.8 W (NS); treadmill duration = 10.1 +/- 3.8 minute
      versus 10.1 +/- 3.6 minute (NS); oxygen consumption at anaerobic threshold = 14.6
      +/- 4.1 mL/kg per minute versus 14.9 +/- 4.6 mL/kg per minute (NS); maximum
      minute ventilation = 49.6 +/- 9L/min versus 46 +/- 12 L/min (NS); and respiratory
      quotient = 1.08 +/- 0.15 versus 1.08 +/- 0.13 (NS). We conclude that, during a 1
      month follow-up period, no difference was found between DDD and dual sensor VVIR
      (QT and activity) pacing modes in CAVB patients with regard to quality-of-life
      and cardiopulmonary performance, though a trend toward an increased sense of well
      being was noted with the DDD mode.

PMID- 8880797
TI  - Assessment of time domain and spectral components of heart rate variability
      immediately before ischemic ST segment depression episodes.
AB  - In an attempt to study autonomic function during the 5-minute period preceding
      ischemic ST segment depression (decreases ST) episodes, we selected 138 decreases
      ST episodes, without preceding decreases ST during the last 15 minutes before
      each episode, from the Holter tapes of 35 patients with multivessel coronary
      artery disease. For the 5-minute period preceding each decreases ST episode, we
      calculated the following heart rate variability (HRV) indices; the mean RR
      interval (RR5), the standard deviation of all RR intervals (SD Index5), the
      corresponding coefficient of variation (CV5), and the natural log (Ln) of the
      spectral components, total power at 0.000 to 0.400 Hz (TP5), low frequency power
      at 0.040 to 0.150 Hz (LF5), high frequency power at 0.150 to 0.400 Hz (HF5), and
      the ratio of the low to high frequency power (LF5/HF5). As HRV indices of the 24
      hour period, we calculated the respective RR, SD Index, CV, LnTP, LnLF, LnHF, and
      Ln LF/HF. RR5, SD Index5, CV5, and Ln TP5 were all significantly lower than RR (t
      = -5.343, p = 3.7 x 10(-7)), SD Index (t = -19.091, p = 1.99 x 10(-40)), CV (t = 
      15.780, p = 1.28 x 10(-32)), and LnTP (t = -3.210, p = 0.0016), respectively.
      LnHF5 was inversely correlated with the magnitude of the decreases ST; r = 
      0.174, P < 0.05, and CV5 was inversely correlated with the natural log (Ln) of
      the ischemic event duration; r = -0.183, P < 0.05. Analogous results were
      obtained for both the painful and silent decreases ST episodes. It is concluded
      that HRV is decreased during the 5-minute period preceding decreases ST episodes,
      and is inversely related with the magnitude and the duration of the *ST.

PMID- 8880798
TI  - A simple method for preoperative assessment of the best fitting electrode length
      in single lead VDD pacing.
AB  - For single lead VDD pacing, electrodes with various distances between the lead
      tip and the floating atrial dipole (AV distance) are available. Using different
      AV distances allows positioning of the atrial dipole in the mid- to high right
      atrium, regardless of the size of the right heart. In this position, reliable
      atrial sensing and rejection of ventricular far-field potentials can be expected.
      A simple test for the preoperative assessment of the best fitting AV distance in
      the individual patient was tested. We studied 24 consecutive patients prior to
      implantation of a VDD pacemaker. With the patient in supine position, a test
      electrode with an AV distance of 13 cm was taped onto the thorax. Under
      fluoroscopic control, it was moved until its course and projection onto the heart
      was equal to that of a ventricular lead. If fluoroscopy then showed a projection
      of the atrial dipole onto the mid- to high right atrium, a lead with a similar AV
      distance of 13 or 13.5 cm was used for implantation. If the atrial dipole
      projected itself too high or too low, a shorter or longer lead had to be
      implanted. The maximum time for the test was 2 minutes, and the maximum
      fluoroscopy time was 15 seconds. According to the test, a lead with an AV
      distance of 13 or 13.5 cm was implanted in 18 of 24 patients, and a lead with an
      AV distance of 15.5 or 16 cm was implanted in 6 of 24 patients. The atrial dipole
      could easily be positioned in the mid- to high right atrium in all patients,
      demonstrating a correct preoperative assessment of the best fitting AV distance.
      Intraoperatively, a P wave amplitude of 3.5 +/- 3.0 mV was measured. The
      described test allows a fast and reliable assessment of the best fitting
      electrode length in single lead VDD pacing.

PMID- 8880799
TI  - Transient complete heart block during radiofrequency ablation of a left lateral
      bypass tract.
AB  - RF catheter ablation of accessory bypass tracts associated with the Wolff
      Parkinson-White syndrome has become an accepted and widespread therapy. When
      bypass tracts are located in the free wall of the left ventricle, a single
      catheter technique may be utilized. A single catheter is placed via the femoral
      artery, across the aortic valve into the left ventricle. Mapping is performed
      during sinus rhythm, and ablation performed at the site of recording of Kent
      bundle activation. We describe a case of a patient with Wolff-Parkinson-White
      syndrome presenting with rapid atrial fibrillation requiring cardioversion. This
      patient subsequently underwent catheter ablation of a left free-wall bypass tract
      using the single catheter technique. At baseline, preexcitation and right bundle
      branch block (RBBB) were present on the ECG. During catheter ablation of the
      accessory pathway, transient complete AV block was seen. This was felt likely to
      be due to trauma to the His bundle, or more likely to the left bundle branch, as
      the ablation catheter crossed the aortic valve. The bypass tract was successfully
      ablated after placement of a temporary right ventricular pacemaker. AV conduction
      resumed with a pattern of RBBB. A temporary right ventricular pacing catheter
      should be placed prior to RF ablation of left-sided bypass tracts when the ECG is
      also suggestive of RBBB.

PMID- 8880800
TI  - Effects of autonomic manipulation on ventricular fibrillation and internal
      cardiac defibrillation thresholds in pigs.
AB  - Autonomic tone may contribute to cardiac arrhythmogenesis and influence the
      efficacy of implantable defibrillators. Fifty-two anesthetized pigs were
      randomized to: (1) methacholine (n = 12); (2) nitroprusside (n = 12); (3)
      phenylephrine (n = 12); (4) carbachol (n = 8); and (5) saline (n = 8).
      Ventricular fibrillation threshold (VFT) and triplicate defibrillation thresholds
      (DFT) were obtained before and during each intervention. Mean (+/- SE) VFT was
      increased with: methacholine (76 +/- 10.6 V vs 39 +/- 7.1 V, P < 0.001);
      phenylephrine (68 +/- 10.5 V vs 38 +/- 6.2 V, P < 0.001); and carbachol (106 +/-
      11.5 V vs 30 +/- 6.5 V, P < 0.0001). Nitroprusside and saline failed to alter
      VFT. Mean (+/- SE) DFT was decreased with: methacholine (7.7 +/- 0.8) vs 9.7 +/-
      0.8 J, P < 0.001); phenylephrine (9.8 +/- 0.9 J vs 11.3 +/- 1.0 J, P < 0.05); and
      carbachol (9.2 +/- 0.7 J vs 12.2 +/- 0.8 J, P < 0.0001), remaining unchanged
      following nitroprusside and saline infusion. Thus, modulation of autonomic tone
      modified arrhythmia susceptibility and the energy necessary for defibrillation,
      increased parasympathetic tone, increased VFT, and decreased DFT. Evaluation of
      autonomic balance, particularly parasympathetic tone, may be useful with the
      implantation of automatic defibrillators.

PMID- 8880801
TI  - Risk of radiation induced skin injuries from arrhythmia ablation procedures.
AB  - Catheter guided ablation of cardiac arrhythmias is an effective and safe
      procedure for the treatment of most supraventricular and selected ventricular
      tachycardias. Because catheter manipulation is fluoroscopically guided, there is
      risk of radiation induced injury, especially during prolonged procedures. The
      Food and Drug Administration has recently issued a bulletin warning of the risks
      of acute skin injury occurring during fluoroscopically guided procedures that
      result in an exposure level exceeding 2 Gray units (Gy). This study was performed
      as an investigation into the risk of radiation induced skin injury during
      arrhythmia ablation procedures. The amount of radiation exposure for 500 patients
      who underwent ablation was calculated based upon fluoroscopy times and the
      entrance dose of radiation (0.02 Gy/min). The mean radiation exposure was 0.93 +/
      0.62 Gy. Although 5.6% of patients (n = 28) received enough radiation exposure
      to reach the threshold dose (2 Gy) for early transient erythema, no clinical
      manifestations of acute radiation induced skin injury were observed. No patients
      achieved the threshold dose for irreversible skin injury. Patients undergoing AV
      node ablation or modification received significantly less radiation (0.39 +/-
      0.40 Gy and 0.79 +/- 0.44 Gy, respectively) than patients undergoing other
      ablation procedures (0.94-1.45 Gy, P < 0.05). There was no association between
      the magnitude of radiation exposure and the presence of underlying heart disease.
      Patients undergoing ablation of accessory pathways were exposed to more radiation
      if there was a right-sided pathway (1.69 +/- 0.93 Gy) compared to other sites
      (0.87-1.24 Gy, P < 0.05). This study demonstrates that the risk of significant
      radiation induced skin injury during arrhythmia ablation procedures is low
      provided that precautions are taken to minimize radiation exposure.

PMID- 8880802
TI  - Recent advances in the electrocardiographic diagnosis of myocardial infarction:
      left bundle branch block and pacing.

PMID- 8880803
TI  - Configuring the ideal personal computer.

PMID- 8880804
TI  - The investigational device saga: a study in public policy evolution.

PMID- 8880805
TI  - Narrow QRS tachycardia with atrioventricular block.

PMID- 8880806
TI  - Implantable cardioverter defibrillator detection during radiofrequency catheter
      ablation of ventricular tachycardia.
AB  - Right ventricular radiofrequency catheter ablation was performed in an ICD
      patient with frequent ventricular tachycardia without prior inactivation of the
      device. The registrations of intracardiac ECG and marker channel were excellent
      during energy delivery: the surface ECG was affected. The device did not show
      dysfunction during and after energy delivery.

PMID- 8880807
TI  - Reversibility of "tachycardia induced cardiomyopathy" following the cure of
      idiopathic left ventricular tachycardia using radiofrequency energy.
AB  - We report a case of incessant ventricular tachycardia with right bundle branch
      block and left axis deviation morphology resulting in severe LV dysfunction and
      congestive heart failure. Radiofrequency ablation of the appropriate site in the
      region of posteroapical part of the LV septum resulted in the cure of the
      arrhythmia. On a 3-month follow-up, the LV size and function returned to normal.

PMID- 8880808
TI  - Permanent mechanical catheter ablation of an accessory pathway in a child.
AB  - Permanent mechanical ablation of an accessory atrioventricular pathway was
      observed in an infant during intracavitary electrophysiological mapping. The
      persistent lack of preexcitation was confirmed during a 15-month follow-up
      period.

PMID- 8880809
TI  - Right ventricular implantable cardioverter defibrillator lead implantation
      through a persistent left superior vena cava.
AB  - A 60-year-old woman required implantation of an ICD because of a hypotensive
      ventricular tachycardia refractory to four different antiarrhythmic drugs.
      Preoperative diagnostics revealed a persistent left SVC as the only major venous
      return from the upper part of the body to the heart. Under local anesthesia, a
      tripolar lead was advanced through the left SVC into the right ventricular apex.
      Following successful testing, an active can ICD device was implanted, which is
      functioning well during a follow-up period of 9 months.

PMID- 8880810
TI  - The shocking lung mass: a case report.
AB  - Two years after implantation of an ICD with epicardial patch leads, a patient
      presented with hemoptysis. The posterior left ventricular patch was found to have
      eroded into lingular segmental bronchus. During thoracotomy, the hardware was
      removed and the bronchus successfully repaired.

PMID- 8880811
TI  - Pacemaker or defibrillator lead implantation.

PMID- 8880812
TI  - STIMAREC report.

PMID- 8880813
TI  - Human factors and outcomes of cardiac surgery.

PMID- 8880815
TI  - Oral transmucosal ketamine: an effective premedication in children.
AB  - The oral cavity offers a simple, painless way of drug administration. For this
      reason, we used oral transmucosal ketamine (5-6 mg.kg-1) for premedication in 25
      children and compared it with intranasal ketamine (5-6 mg.kg-1), placebo and
      intramuscular ketamine (5-6 mg.kg-1). Oral transmucosal ketamine (OTK) provided
      effective sedation, facilitated i.v. line insertion and was accepted with
      pleasure by the patients (as lollipops). The lollipops produced a slight increase
      in gastric volumes but did not affect gastric pH. In conclusion OTK has been
      shown to be an effective, harmless preoperative medication in paediatric
      patients.

PMID- 8880814
TI  - The use of additives to local anaesthetic solutions for caudal epidural blockade.

PMID- 8880816
TI  - The influence of the age of the rat on the neuromuscular response to mivacurium
      in vitro.
AB  - The effective concentrations of mivacurium induced neuromuscular block were
      studied in the phrenic nerve-hemidiaphragm preparations of forty male Sprague
      Dawley rats in four groups according to body weight, 10 g, 25 g, 100 g, and 200
      g. Mivacurium was added to the Krebs' solution to obtain an initial concentration
      of 0.275 microgram.ml-1 (2.5 x 10(-7) mole.litre-1). Thereafter, the
      concentration of mivacurium was increased in increments to obtain more than 90%
      neuromuscular twitch inhibition at 0.1 Hz. Data were analysed by probit and
      logistic models. The two statistical techniques yielded very similar results,
      almost identical values of EC50 and EC95. There were significant decreases in the
      effective concentrations of mivacurium needed to depress the twitch response in
      neonatal rats (10 g) compared to older rats. No significant differences were
      observed between 25, 100 and 200 g rats. We conclude that the neonatal
      neuromuscular junctions of rats show increased sensitivity to mivacurium related
      to pharmacodynamic factors.

PMID- 8880817
TI  - Cisatracurium during halothane and balanced anaesthesia in children.
AB  - Cisatracurium, 51W89, is one of the ten stereoisomers of Tracrium which, unlike
      atracurium, has been reported to have a lack of histamine mediated cardiovascular
      effects at doses as high as 8 x ED95 in adults. We compared the time-course of
      neuromuscular effects of 80 micrograms.kg-1 or 100 micrograms.kg-1 cisatracurium
      during N2O-O2-halothane or N2O-O2-opioid anaesthesia, respectively, in 32
      children 2-12 years old. Neuromuscular function was monitored by evoked adductor
      pollicis EMG. Even-numbered patients (n = 16) were allowed to obtain full
      spontaneous recovery of neuromuscular function and odd-numbered patients (n = 16)
      received neostigmine 45 micrograms.kg-1 together with glycopyrrolate at the time
      of 25% EMG recovery. Data are expressed as median with 10th to 90th percentile
      range. Cisatracurium had an onset time (time from administration to maximal
      effect) of 2.2 (1.7-3.8) or 2.3 (1.8-4.9) min, a clinical duration (time to 25%
      EMG recovery) of 34 (22-40) or 27 (24-33) min, and a spontaneous 25-75% recovery
      time (time from 25 to 75% EMG recovery) of 11 (9-13) or 11 (7-12) min during
      halothane or balanced anaesthesia, respectively (NS). Train-of-four ratio
      recovered to 0.70 in 2.5 (1.8-3.0) or 3.2 (2.1-4.3) min following neostigmine
      during halothane or balanced anaesthesia, respectively (NS). Changes in blood
      pressure or heart rate following cisatracurium were negligible. We regard
      cisatracurium as a safe and promising intermediate duration muscle relaxant the
      effects of which can easily be reversed with neostigmine.

PMID- 8880818
TI  - Clinical characteristics and biotransformation of sevoflurane in paediatric
      patients during antiepileptic drug therapy.
AB  - Patients with epilepsy on long term antiepileptic drug (AED) therapy deserve
      special consideration not only concerning seizure control but also the effect on
      anaesthetic metabolism and hepatorenal functions. In the present study, we
      examined the effects of sevoflurane anaesthesia on plasma inorganic fluoride (F-)
      level and hepatorenal function in patients with and without AED therapy. Twenty
      two patients (12 with AEDs = AED group, and ten without AEDs = control group = C
      group), ASA I, who were free of hepatorenal disease, received approximately 2-3 h
      sevoflurane anaesthesia. Plasma F- analysis was performed at the stages of: 1)
      induction of anaesthesia, 2) conclusion of anaesthesia, 3) 15 h after the
      conclusion of anaesthesia, using an ion-selective electrode calibrated with a
      standard solution of sodium fluoride. Pre- and postoperative hepatic (aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, total
      bilirubin) and renal (blood urea nitrogen, creatinine) function was tested. There
      were no significant differences between the two groups in the average age (AED
      group = 9.4 and control group = 10.1 y.o.), body weight, duration of anesthesia,
      and MAC hours (2.6 and 2.4). The mean peak F- levels were 15.5 and 13.6 microM,
      in AED and C groups (not significant), respectively. No patient exhibited F-
      values greater than 50 microM, the hypothetical nephrotoxic threshold. The
      patients showed no abnormal values either in hepatic or renal function tests
      postoperatively. These results suggest approximately 2-3 h sevoflurane
      anaesthesia to be safe in patients taking AEDs.

PMID- 8880819
TI  - Oxygen enrichment of entrained room air during Venturi jet ventilation of
      children undergoing bronchoscopy.
AB  - Intermittent oxygen jet ventilation at an inspiratory:expiratory ratio of 1:3 was
      used to ventilate 15 children undergoing rigid Storz bronchoscopy for removal of
      inhaled foreign body. Oxygenation of the patient was continuously monitored by
      pulse oximetry. In all children SpO2 was above 95% when the bronchoscope was
      above the carina. When the bronchoscope was introduced into one of the bronchi,
      SpO2 decreased to 70-85% in five children. Delivery of a continuous flow of
      oxygen via a T-piece attached to the side-arm of the bronchoscope increased the
      SpO2 > 95% in the five children. Oxygen jet ventilation during bronchoscopy is
      based on the Venturi principle; the oxygen jet will entrain room air from the
      side arm of the bronchoscope which functions as an entrainment orifice. This will
      decrease the FIO2. The FIO2 can be increased by flowing oxygen continuously via
      the T-piece attached to the side arm of the bronchoscope.

PMID- 8880820
TI  - Midazolam following open heart surgery in children: haemodynamic effects of a
      loading dose.
AB  - Our objective was to establish the safety and effectiveness of a loading dose of
      midazolam for postoperative sedation of children recovering from open heart
      surgery; a prospective randomized placebo-controlled double-blind study was done
      with subjects randomized to three groups according to loading dose. I = 0.08
      mg.kg-1; II = 0.04 mg.kg-1; and III = 0.00 mg.kg-1 (placebo). An open label
      continuous midazolam infusion protocol followed. Haemodynamic parameters were
      monitored. The study was discontinued following an adverse event involving the
      23rd subject. When data for all 23 subjects were combined, there was a mean
      decrease of 10% in blood pressure (BP) 30 min after the loading dose (P < 0.001).
      Heart rate change was less significant. Clinicians identified four hypotensive
      episodes as temporally associated with the midazolam load, two each in Groups I
      (0.08 mg.kg-1) and III (placebo). One subject in Group I (the 23rd) became
      hypotensive within five min of receiving the loading dose, had a difficult
      clinical course and died four weeks postoperatively. We cannot conclude that the
      loading dose of midazolam had any systematic haemodynamic effect in our study
      population. Although the clinical course of the 23rd subject suggests a subset of
      more susceptible children (those who receive opioid analgesia with midazolam, are
      volume-restricted, and/or undergo more complex forms of surgical correction),
      many critical care patients are inherently physiologically unstable, and
      concluding clinically that blood pressure fluctuation is drug related may be
      erroneous.

PMID- 8880821
TI  - Heart rate variability in premature neonates pre-and postmethylxanthine
      administration.
AB  - Methylxanthines are used to treat or prevent respiratory failure (apnoea) in
      premature infants both perinatally and perioperatively. Heart rate variability
      (HRV) is being increasingly used to measure autonomic function. In this study
      various indices of HRV were compared pre- and postmethylxanthine dosing in 22
      infants (aged 24-36 weeks). HRV significantly increased postdosing, particularly
      in the high frequency (HF) band (P = 0.001 by ANOVA). This increase was more
      pronounced in the sickest infants. This pattern of increased HRV and %HF is the
      same that occurs with normal maturation. This suggests that methylxanthine may
      stimulate and normalize autonomic function.

PMID- 8880822
TI  - Left ventricular functions are not impaired after lumbar epidural anaesthesia in
      young children.
AB  - We studied the haemodynamic and cardiovascular effects of epidural anaesthesia
      with plain bupivacaine 0.75 ml.kg-1 in 13 unpremedicated ASA 1 children using
      measurements of heart rate, blood pressure and M-mode echocardiography. Under
      general anaesthesia, M-mode echocardiographic evaluation of left ventricular
      function in each patient was performed at four points (after general anaesthesia,
      point A; 5 min, 10 min and 25 min after epidural anaesthesia, point B; point C;
      and point D, respectively). Results were compared between point A and B, A and C,
      A and D, B and C, B and D, C and D. HR decreased significantly at 10 min (point
      C) and 25 min (point D) and MBP decreased at 5 min (point B) and 10 min (point D)
      compared to point A. No other M-mode cardiographic indices were changed at any
      point. Epidural anaesthesia using 0.25% bupivacaine 0.75 ml.kg-1 did not affect
      LV function in young children.

PMID- 8880823
TI  - Anisocoria during isoflurane anaesthesia in a six-year-old girl.

PMID- 8880824
TI  - Severe hypoglycaemia associated with preoperative fasting and intraoperative
      propranolol. A case report and discussion.

PMID- 8880825
TI  - Respiratory depression following administration of low dose buprenorphine as
      postoperative analgesic after fentanyl balanced anaesthesia.
AB  - Opioids are among the most ancient and widely used drugs in anaesthesiology. The
      pharmacology of opioid analgesics and their receptors is a complex and not fully
      understood matter; even more complex are the interactions between different
      classes of opioids at both molecular and clinical levels. We want to report here
      a clinical observation to emphasize the importance of the theoretical basis of
      anaesthesiology. This paper contains a clinical observation of respiratory
      depression following the administration of buprenorphine as postoperative
      analgesic after balanced anaesthesia with fentanyl. The observed case is
      interpreted in the light of the pharmacokinetics and pharmacodynamics of the
      different classes of opioid drugs (agonists, agonists-antagonists, antagonists)
      and of the interactions with their respective receptors.

PMID- 8880827
TI  - Forced-air warming system for perioperative use in neonates.

PMID- 8880826
TI  - Intrathecal morphine for postoperative analgesia in an infant with
      bronchopulmonary dysplasia following upper abdominal surgery.
AB  - We present a case of severe bronchopulmonary dysplasia in which intrathecal
      morphine was successfully used for analgesia after a Nissen fundoplication and
      gastrostomy. Various options for anaesthesia are discussed with the knowledge
      that two previous procedures had been complicated by congestive cardiac failure
      and increased respiratory failure.

PMID- 8880828
TI  - Hyperthermia during sevoflurane anaesthesia in arthrogryposis multiplex congenita
      with central nervous system dysfunction.

PMID- 8880829
TI  - Variation in opioid use during PCA in adolescents.

PMID- 8880830
TI  - Windup and central sensitization are not equivalent.

PMID- 8880831
TI  - Current views on neurostimulation in the treatment of cardiac ischemic syndromes.
AB  - Most clinicians are still unacquainted with the beneficial effects of
      neurostimulation as an additional therapeutic strategy for severe angina
      pectoris. Patients with therapeutically refractory angina pectoris suffer from
      chest discomfort during minimal exercise, despite maximal tolerated antianginal
      drug therapy (at least 2 out of a beta-blocker, calcium-antagonist or long-acting
      nitrate). In these patients, revascularization procedures, such as a percutaneous
      transluminal coronary angioplasty or coronary artery bypass surgery, are often
      technically impossible because of diffuse coronary artery disease or should be
      withheld as a consequence of absolute contraindications such as severe left
      ventricular dysfunction. All patients have inoperable multivessel disease,
      experienced one or more myocardial infarctions, and were treated by earlier
      invasive interventions. This group of patients are severely physically and
      psychologically disabled by their intractable angina pectoris. Available
      published data and the neurostimulation experience of the authors are reviewed in
      relation to the treatment of cardiac ischemic syndromes. We conclude that
      neurostimulation is an effective therapeutic adjuvant for patients with severe
      angina pectoris unresponsive to standard treatment. This treatment modality
      appears to be safe, and a promising tool for other ischemic cardiac syndromes.

PMID- 8880832
TI  - Hemodynamic and sympathetic nerve responses to painful stimuli in normotensive
      and borderline hypertensive subjects.
AB  - Observations in animals and humans show that pain sensitivity might be lower (and
      pain tolerance higher) in hypertensive as compared to normotensive subjects. One
      hypothesis, derived from experimental studies, assumes that enhanced activation
      of baroreceptors leads to an enhanced central inhibition. A central hypothesis
      assumes changes in the central (endogenous) control of the nociceptive system. To
      investigate these two hypotheses we quantitatively assessed the minute-by-minute
      changes in mean arterial pressure (MAP), central venous pressure (CVP) heart rate
      (HR), muscle sympathetic nerve activity (MSNA), and individual pain ratings
      during noxious mechanostimulation in 10 normotensive (NT) and 13 borderline
      hypertensive (BH) subjects. Linear regression analysis indicated a close negative
      correlation for the overall data between resting levels of MAP and pain ratings
      (r = -0.57, P < 0.0001). The BH group exhibited a lower pain sensitivity compared
      to the NT group (P < 0.001). The extent of baroreceptor activation during the
      application of pain was not different between the two groups (P = NS) as assessed
      by almost identical increases in MAP (+8 +/- 1 vs. +9 +/- 1 mmHg NT vs. BH
      group), CVP (+0.7 +/- 0.1 vs. +0.5 +/- 0.1 mmHg), HR (+2 +/- 1 vs. +2 +/- 1
      beats/min), and MSNA (+5 +/- 1 +4 +/- 1 bursts/min). The NT subjects exhibited
      significant correlations between the pain ratings and the increases in MAP (r =
      +0.52; P < 0.05) and MSNA (r = +0.49; P < 0.05) whereas the BH subjects did not
      show such a relationship. Thus, the increased pain tolerance in human
      hypertension cannot be explained by hemodynamically mediated differences in the
      activation of baroreceptors or by an altered baroreflex sensitivity during the
      application of pain. We conclude, that the reduced pain sensitivity in
      hypertensive humans is more likely related to central changes.

PMID- 8880833
TI  - Suppression of an inhibitory jaw reflex by the anticipation of pain in man.
AB  - Electromyographic recordings (EMGs) were made from the active masseter muscle, of
      the inhibitory reflex evoked by application of electrical stimuli to the skin of
      the upper lip in 15 human subjects. In control sequences, the reflex had a mean
      latency and duration (+/- S.E.M.) of 45.4 +/- 1.3 msec and 47.9 +/- 2.8 msec,
      respectively. Significant decreases in the reflex as well as increases in heart
      rate and anxiety levels assessed by a visual analogue scale, occurred when the
      subjects were stressed by the anticipation of receiving painful electrical
      stimuli above the ankle (P < 0.00005; Student's t-tests). During such sequences,
      the magnitude of the reflex measured by integration of the EMG, was reduced by
      47.7 +/- 5.6%. This effect involved a reduction in both the duration and depth of
      the inhibitory wave. It occurred regardless of whether the painful stimuli were
      applied during or after the recording of the reflex and of whether the baseline
      activity in the muscle was inadvertently raised or lowered during the stressful
      sequences. It is concluded that stress induced by the anticipation of pain, can
      markedly reduce an inhibitory jaw reflex in man by exerting an influence on the
      reflex pathway prior to the motoneurones.

PMID- 8880834
TI  - Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification.
AB  - The hypervigilance model of pain perception states that chronic pain patients
      have a heightened sensitivity to pain (e.g. low threshold and tolerance) because
      of increased attention to external stimulation and a preoccupation with pain
      sensations. This study tested the hypothesis that individuals with fibromyalgia,
      a chronic pain disorder of undetermined origin, have a generalized hypervigilant
      pattern of responding that extends beyond the pain domain. Twenty fibromyalgia
      out-patients, 20 rheumatoid arthritis (RA) patients, and 20 normal controls
      served as subjects. The RA and normal control subjects were age and sex matched
      to the fibromyalgia patients. Subjects were tested for pain tolerance, pain
      threshold, and noise tolerance and were asked to complete a number of
      questionnaires that assessed hypervigilance. As predicted, the responses of the
      fibromyalgia patients to both the pain and auditory stimuli were consistent with
      the generalized hypervigilance hypothesis. These patients had significantly lower
      threshold and tolerance values than the RA patients, who in turn, had lower
      values than the normal control subjects. The results of the psychological
      questionnaires revealed that the fibromyalgia and RA patients preferred lower
      levels of external stimulation than the control subjects. The outcome of this
      study supports the generalized hypervigilance hypothesis, suggesting that
      fibromyalgia patients have a perceptual style of amplification. The implications
      of these findings for understanding the role of biological, cognitive, and
      perceptual factors in pain disorders are discussed.

PMID- 8880835
TI  - Anxiety and pain: attentional and endorphinergic influences.
AB  - The role of attentional mechanisms and endogenous opioids in the influence of
      anxiety on acute pain sensation was investigated. Forty-five spider phobics
      received mildly painful electrical stimulation. The opioid antagonist naltrexone
      or placebo was administered between subjects to examine an analgesia due to
      anxiety-induced endorphinergic activity, while anxiety and focus of attention
      were manipulated within subjects. In accordance with previous research, pain
      ratings and skin conductance responses (SCRs) were not influenced by anxiety when
      focus of attention was controlled for. Attention towards pain led to an increase
      in subjective pain as opposed to distraction from pain. SCRs, however, were
      increased in the distraction conditions, probably due to heightened
      unexpectedness. Further, both high and low anxiety resulted in an analgesia
      compared to the pretest in the placebo condition, which was reversed by a low
      dose of naltrexone, but not by a high dose. Apart from possible agonist
      properties of high doses of naltrexone, this effect suggests an opioid-induced
      analgesia. It remains to be demonstrated whether this was due to endogenous
      opioids released during high anxiety.

PMID- 8880836
TI  - Rectal afferent function in patients with inflammatory and functional intestinal
      disorders.
AB  - Chronic symptoms of abdominal pain and discomfort are reported by patients with
      inflammatory bowel disease (IBD) and functional disorders of the gut, such as
      Irritable Bowel Syndrome (IBS). It has recently been suggested that transient
      inflammatory mucosal events may result in long-lasting sensitization of visceral
      afferent pathways. To determine the effect of recurring intestinal tissue
      irritation on lumbosacral afferent pathways, and to identify a plausible
      mechanism that could account for the overlap in symptomatology between IBD and
      IBS, we compared rectal afferent mechanisms in patients with Crohn's disease
      (inflammation limited to the ileum) with those observed in patients with diarrhea
      predominant IBS. Continuous volume ramp and phasic pressure step distension of a
      rectal balloon were performed in 9 healthy male control subjects, 12 male
      patients with isolated ileal Crohn's disease and 9 male patients with diarrhea
      predominant IBS using an electronic visceral stimulation device. The response of
      rectal afferents to distension was evaluated by measuring thresholds for the
      perception of physiological (stool) and aversive (discomfort) sensations,
      viscerosomatic referral patterns, skin conductance responses, receptive
      relaxation, and rectoanal reflex responses. In response to slow ramp distension,
      thresholds for aversive sensations were significantly higher in Crohn's disease
      patients, but similar between the two other groups. In response to rapid phasic
      distension, IBS patients reported discomfort at lower distension pressures, while
      all other thresholds were similar between groups. Skin conductance responses to
      aversive distension were greatly reduced in Crohn's disease patients while IBS
      patients had greater responses when compared to normals. Changes in
      viscerosomatic referral patterns and receptive relaxation rate were similar in
      Crohn's disease and IBS patients. These findings demonstrate that chronic ileal
      inflammation is associated with increased thresholds for discomfort and greatly
      diminished systemic autonomic reflex responses. In contrast, IBS patients show
      lowered thresholds for discomfort associated with increased autonomic responses.
      The findings in Crohn's patients may result from descending bulbospinal
      inhibition of sacral dorsal horn neurons in response to chronic intestinal tissue
      irritation.

PMID- 8880837
TI  - Inflammatory mediators potentiate pain induced by experimental tissue acidosis.
AB  - Electrophysiological evidence from cutaneous nociceptors suggested a synergism
      between excitatory actions of inflammatory mediators (IM) and low pH. In human
      skin it is possible to induce constant ongoing pain with continuous infusion of
      acid buffer. This method was used to study the interaction with mediators of
      inflammation psychophysiologically. A skin area on the palmar forearm of 6
      subjects (either gender, age 22-35 years) was continuously infiltrated with a
      phosphate buffered electrolyte solution (pH 5.2) using a motorized syringe pump
      that was adjusted so as to produce constant pain of about 20% on a visual analog
      scale (VAS; extending from 'no' to 'unbearable pain'). Pain was assessed on the
      VAS at 10-sec intervals; the rating was called up by means of an acoustic signal.
      An additional cannula was placed in the skin before the infusion of acidic buffer
      started. Injections of an acidic combination of IM (BK, 5-HT, HIS, PGE2) 0.2 ml
      were then given through the cannula at intervals of 10 min in a randomized double
      blind order of concentrations. The other arm was used for negative control, i.e.
      IM in neutral solution were injected into normal skin continuously infiltrated
      with a buffer solution at pH 7.4. The IM induced dose-dependent, transient
      burning pain on both arms-markedly more intense and prolonged, however, in the
      acidotic skin (P < 0.004, U-test). The difference corresponded to a 10-fold
      increase in algogenic potency with 10(-7) M IM, being smaller with 10(-6) and 10(
      5) M concentration. The interaction between low pH and IM was mutual: additional
      injections of plain phosphate buffer (pH 5.2) into the acidotic skin were
      significantly more painful (20-fold) after application of IM than under control
      conditions. Thus, we tend to conclude that it is the inflammatory mediators that
      potentiate the algogenic effect of low pH rather than vice versa. Tissue acidosis
      appears as a dominant factor in inflammatory pain.

PMID- 8880838
TI  - Predictive utility of the CSQ in low back pain: individual vs. composite
      measures.
AB  - Researchers have typically used factor-analytic composite measures of coping,
      instead of individual scales, to predict rehabilitation outcome. There are,
      however, both advantages and disadvantages to using individual or composite
      scores. This study extended the findings of Jensen et al. (1992), by
      prospectively comparing the individual and composite scores of the Coping
      Strategies Questionnaire (CSQ) in the prediction of 4 types of adjustment to low
      back pain. Two-hundred patients completed the CSQ, the Oswestry Index, the SCL
      90R, and 4 lifting tasks at admission and discharge from a multidisciplinary pain
      clinic. Return to work was determined at 9-month follow-up. The CSQ scales were
      factor-analyzed to devise composite indices, and the 3 resultant factors were
      compared to the individual scales in the prediction of pain and other outcomes.
      The results indicated that the relative predictive utility of the composite or
      individual scales depended on which outcome measure was used to define
      adjustment.

PMID- 8880839
TI  - Influence of previous pain experience on the episode incidence of low back pain:
      results from the South Manchester Back Pain Study.
AB  - BACKGROUND: A pathological cause cannot be identified for most new episodes of
      low back pain (LBP) presenting to the general practitioner. One important
      potential influence on susceptibility is previous pain experience. To accurately
      investigate the contribution of this phenomenon to the onset of new episodes of
      LBP a prospective population study is required. AIMS: To determine the
      relationship of prior pain in the back and other musculoskeletal sites to risk of
      subsequent new episodes of LBP. METHODS: The population studied included all 2715
      adults from the South Manchester Back Pain Study who were free of LBP during the
      month prior to the baseline survey. At baseline a detailed musculoskeletal pain
      history was obtained. New episodes of LBP over the subsequent 12 months were
      ascertained by: (i) prospectively monitoring all primary care consultations in
      the study cohort (consulting episodes) and (ii) a follow-up survey after 1 year
      to determine new episodes during that 12-month period not leading to consultation
      (non-consulting episodes). RESULTS: The 12-month cumulative incidence of new
      consulting episodes was 3% in males and 5% in females, and for new non-consulting
      episodes 31% in males and 32% in females. Those with a history of previous LBP
      had twice the rate of new episodes, both consulting and non-consulting, compared
      to those with no LBP in the past. Neck pain or pain in other musculoskeletal
      sites at baseline also doubled the risk of a subsequent new episode of LBP.
      Adjusting for psychological distress and the other pain variables had little
      influence on the findings. CONCLUSION: In those currently free of LBP a previous
      history of the symptom substantially increases the risk of a further episode,
      with pain in other sites an equally strong independent predictor of subsequent
      LBP.

PMID- 8880840
TI  - Pain during mammography: characteristics and relationship to demographic and
      medical variables.
AB  - Reports of pain during mammography show that there is great variability in both
      the incidence of reported pain (0.2-62%) and the intensity of that pain. Much of
      that variability may be due to the measures used to rate mammography pain. This
      is the first study that has examined the incidence, quality and intensity of
      mammography pain using a variety of pain measures. A sample of 119 women
      undergoing screening mammography was studied using four pain scales, three well
      validated measures frequently used in the pain research literature as well as a
      pain/discomfort measure frequently reported in the radiology literature. A large
      proportion (up to 91%) of women report having some degree of pain during
      mammography. The intensity of that pain was typically in the low to moderate
      range, but a small proportion of women (< 15%) reported intense pain. The
      incidence of reported pain was related to the pain measure used. Pain measures
      that provided a woman with many options for reporting pain were associated with a
      higher incidence of pain than a scale that provided only one or two options.
      Thus, some of the variability in reported incidence of pain during mammography
      can be explained by the pain scale used in the study. Demographic and medical
      variables could explain 18-20% of the variance in mammography pain. Two of the
      variables that were shown to consistently predict a painful mammographic
      experience were (1) average pain at the last mammogram and (2) breast density.
      This study demonstrated that the pain measure selected for use in a particular
      study may depend on the population being studied. A college education was found
      to be an important predictor of pain scores on the McGill Pain Questionnaire.
      Thus, this pain measure may be of limited usefulness in studying a population of
      women with little formal education.

PMID- 8880841
TI  - Pain after breast surgery: a survey of 282 women.
AB  - Breast surgery is a common procedure performed in women. Many women who undergo
      breast surgery suffer from ill-defined pain syndromes. Although there exists a
      few reports on the incidence of post mastectomy pain, there are no published
      reports on chronic pain after breast reconstruction. This investigation attempts
      to characterize the pain after four types of breast surgery: (1) mastectomy, (2)
      mastectomy with reconstruction, (3) cosmetic augmentation, and (4) breast
      reduction. A questionnaire was mailed to 479 women who underwent breast surgery
      at the University of California, San Diego Medical Center between January 1988
      and December 1992. A second mailing was sent to women who did not respond to the
      first mailing. Women were divided into four groups; mastectomy, mastectomy with
      reconstruction, cosmetic augmentation, and breast reduction. In the mastectomy
      and mastectomy with reconstruction groups, only women who had a lumpectomy with
      axillary dissection, a modified radical mastectomy, or a radical mastectomy were
      used in the study. 59% of the women responded. The incidence of pain occurring at
      least one year after surgery in the mastectomy + reconstruction group (49%) was
      significantly higher than the mastectomy (31%) and breast reduction (22%) groups.
      Thirty-eight percent of the women with breast augmentation complained of pain.
      Women who had reconstruction using breast implants had a higher incidence of pain
      (53%) than those without (30%). The pain incidence in women who had
      reconstruction without implants was identical to women who had a mastectomy
      without reconstruction. There was no relationship between the use of silicone or
      saline implants and pain (22% and 33% respectively). However, the submuscular
      placement of the implants resulted in a significantly higher incidence of pain
      (50%) than the subglandular placement (21%). Of the women that reported pain, arm
      pain was significantly higher in the mastectomy and mastectomy + reconstruction
      group (56% and 42%, respectively) as compared to the breast reduction group (0%).
      Most patients reported intermittent pain in all groups. Of the women that
      reported pain, the mastectomy and mastectomy + reconstruction group had higher
      pain related to movement (41% and 42%, respectively) than the augmentation and
      breast reduction groups (15% and 9%, respectively). The peak pain intensity was
      significantly higher in the augmentation group as compared to the mastectomy
      group. Our incidence of post mastectomy pain is higher than most reports. The
      incidence of breast pain is highest in the mastectomy + reconstruction and
      augmentation groups which is assumed to be secondary to breast implants. Every
      effort should be made to achieve the best cosmetic result in breast
      reconstruction which in many cases justifies the use of breast implants. However,
      these women should be counseled on the possibility of developing chronic pain.

PMID- 8880842
TI  - The relationship between symptoms of post-traumatic stress disorder and pain,
      affective disturbance and disability among patients with accident and non
      accident related pain.
AB  - Recent studies have reported a high prevalence of symptoms of post-traumatic
      stress disorder (PTSD) among individuals with chronic pain. Studies suggest that
      persons with pain and PTSD also display higher levels of affective disturbance.
      In the present study we examined self-reports of pain, affective disturbance, and
      disability among pain patients with and without symptoms of PTSD. Patients
      without PTSD symptoms were further subdivided into persons whose pain was the
      result of an accident or insidious in onset. Thus, three groups were examined:
      (1) persons with accident related pain and high PTSD symptoms (Accident/High
      PTSD); (2) persons with no or few symptoms of PTSD whose pain was accident
      related (Accident/Low PTSD); and (3) patients whose pain was not accident related
      and did not have PTSD symptoms (No Accident). No Accident patients were older
      than persons with accident related injuries, and both accident related pain
      groups were more likely than No Accident patients to be involved in litigation or
      receiving compensation. Thus, these variables were controlled for in the
      statistical analyses. Self-report of pain was also included as a covariate in the
      analyses examining group differences in affective disturbance and disability.
      Accident/High PTSD patients displayed higher levels of self-reported pain
      compared to the other two groups. The Accident/High PTSD group also had the
      highest levels of affective disturbance. Both accident groups tended to report
      greater disability compared to patients whose pain was not accident related.
      These findings suggest that PTSD symptoms in chronic pain patients are associated
      with increased pain and affective distress. Accident related pain, even without
      the presence of PTSD symptoms, appears to be associated with greater disability.
      The results indicate that the identification and treatment of PTSD symptoms in
      refractory pain patients may be a critical albeit subtle factor in the effective
      management of suffering and disability in this population.

PMID- 8880843
TI  - The effect of experimental jaw muscle pain on postural muscle activity.
AB  - The purpose of this study was to examine whether tonic muscle pain of an
      intensity at least as great as that reported by the majority of chronic muscle
      pain patients causes an increase in postural electromyographic activity of the
      affected musculature. Twenty young adults volunteered for experiments, knowing
      that they involved experimental pain. We chose a controlled, two-period crossover
      and repeated measures design involving four experimental conditions: (1) baseline
      1, (2) tonic experimental muscle pain, (3) sham pain, and (4) baseline 2.
      Subjects were randomly assigned to one of two sequential orders that differed
      with respect to whether tonic pain preceded sham pain or vice versa. At the
      within-subject level, the condition (baseline 1, sham pain, tonic pain, baseline
      2) had a statistically significant effect on mean rms electromyographic activity
      at all four recording sites. We found that postural activities at all four
      recording sites, left/right masseter and left/right anterior temporalis were
      statistically different from baseline 1 and 2 during tonic pain (P < 0.004, s.; P
      < 0.024, s.). However, postural activities during tonic pain and sham pain were
      not significantly different from each other (P < 0.493, n.s.). We concluded that
      our data do not support the hyperactivity model which assumes a re-enforcing link
      between pain and muscle hyperactivity.

PMID- 8880844
TI  - Faking a profile: can naive subjects simulate whiplash responses?
AB  - The psychological symptom checklist, the SCL-90-R (Derogatis 1983), has been used
      to assess patients with a number of chronic pain syndromes. For whiplash injury,
      a characteristic profile has been found (Wallis et al. 1995). However, there is
      still a belief that patients with neck pain following whiplash injury may be
      malingering, and therefore the utility of the SCL-90-R as a screen for possible
      malingering is assessed here. Forty pain-free university students were asked to
      simulate chronic pain 6 months after a motor vehicle accident in order to ensure
      compensation. The SCL-90-R, McGill Pain Questionnaire and a visual analogue pain
      scale were used. Students' scores were compared with those of a group of 132
      whiplash patients (Wallis et al. 1995). Differences between the two groups were
      striking; the students scored significantly higher than patients on all subscales
      of the SCL-90-R and on the visual analogue pain scale (Mann-Whitney P-values all
      less than 0.001). However, pain scores for both groups on the McGill Pain
      Questionnaire were similar. The conclusion was that it is very difficult for an
      ingenuine individual to fake a psychological profile typical of a whiplash
      patient.

PMID- 8880845
TI  - Deriving dichotomous outcome measures from continuous data in randomised
      controlled trials of analgesics.
AB  - Reports of RCTs of analgesics frequently describe results of studies in the form
      of mean derived indices, rather than using discontinuous events--such as number
      or proportion of patients with 50% pain relief. Because mean data inadequately
      describe information with a non-normal distribution, combining mean data in
      systematic reviews may compromise the results. Showing that dichotomous data can
      reliably be derived from mean data, at least in acute pain models, indicates that
      more meaningful overviews or meta-analysis may be possible. This study
      investigated the relationship between continuous and dichotomous analgesic
      measures in a set of individual patient data, and then used that relationship to
      derive dichotomous from continuous information in randomised controlled trials
      (RCTs) of analgesics. Individual patient information from 13 RCTs of parallel
      group and crossover design in acute postoperative pain was used to calculate the
      percentage of the maximum possible pain relief score (%maxTOTPAR) and the
      proportion of patients with greater than 50% pain relief (> 50%maxTOTPAR) for the
      different treatments. The relationship between the measures was investigated in
      45 actual treatments and 10,000 treatments simulated using the underlying actual
      distribution; 1283 patients had 45 separate treatments. Mean %maxTOTPAR
      correlated with the proportion of patients with > 50%maxTOTPAR (r2 = 0.90). The
      relationship calculated from all the 45 treatments predicted to within three
      patients the number of patients with more than 50% pain relief in 42 of 45
      treatments, and 98.8% of 10,000 simulated treatments. For seven effective
      treatments, actual numbers-needed-to-treat (NNT) to achieve > 50%maxTOTPAR
      compared with placebo were very similar to those derived from calculated data.

PMID- 8880846
TI  - Developing a database of published reports of randomised clinical trials in pain
      research.
AB  - A database of randomised clinical trials (RCTs) in pain research published from
      1950 to 1990 was created following an extensive literature search. By applying a
      refined MEDLINE search strategy from 1966 to 1990 and by hand-searching more than
      1,000,000 pages of a total of 40 biomedical journals published during the period
      1950-1990, more than 8000 RCTs were identified. The RCTs were published in more
      than 800 journals and over 85% appeared between 1976 and 1990. If the trend of
      the last 15 years persists, a total of more than 15 000 RCTs will be published in
      pain relief by the year 2000. A detailed description of methods to ensure
      efficient use of resources during the identification, retrieval and management of
      the information in pain relief and other fields is given. Emphasis is made on the
      importance of refining MEDLINE search strategies, on the use of volunteers to
      hand-search journals and on careful monitoring of each of the steps of the
      process. The potential uses of the database to guide clinical and research
      decisions are discussed.

PMID- 8880847
TI  - Ibuprofen compared with ibuprofen plus caffeine after third molar surgery.
AB  - OBJECTIVES: To compare the relative merits of single doses of ibuprofen and
      ibuprofen plus caffeine in the treatment of pain after third molar removal.
      DESIGN: Randomised, double-blind, placebo-controlled, single-dose parallel-group
      comparison of placebo, ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50,
      100 or 200 mg of caffeine. SUBJECTS: 161 patients undergoing lower third molar
      removal. RESULTS: All active treatments produced significant analgesia and mood
      elevation compared with placebo. There was no significant difference in the
      effects of 200 and 400 mg of ibuprofen. Adding caffeine to 200 mg ibuprofen
      produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200
      mg alone. Ten patients reported 11 adverse effects, none in the highest caffeine
      dose group. CONCLUSIONS: Caffeine increased the analgesic effect of ibuprofen 200
      mg, through an earlier onset of analgesic effect. This was achieved in this
      single dose context without problematic adverse effects.

PMID- 8880848
TI  - Effects of systemic morphine on responses of primates to first or second pain
      sensations.
AB  - Despite evidence that systemic morphine preferentially attenuates second pain
      sensations that are presumed to result from activation of unmyelinated (C)
      nociceptors, most animal models of nociception elicit sensations that result from
      or are dominated by activation of myelinated (A-delta) nociceptors. Therefore,
      methods were developed to directly compare the effects of morphine on late
      (second) pain sensations and early onset (first) pain sensations in an animal
      model. In order to establish appropriate stimulus parameters, human
      psychophysical experiments compared characteristics of sensations evoked by brief
      (pulsed) thermal stimulation and ramp-and-hold thermal stimulation. Brief (500
      msec) contact of a pre-heated thermode with the skin produced late pain
      sensations with peripheral conduction velocities in the range of C afferents, as
      estimated by latencies from stimulation of proximal and distal sites on the leg.
      The sensations evoked by brief contact increased with successive contacts
      (pulses) at 0.4 Hz, demonstrating temporal summation of sensation intensity.
      Pretreatment of the skin with capsaicin enhanced the late pain sensations from
      pulsed stimulation. In contrast, peak sensations evoked by ramp-and-hold thermal
      stimulation were evoked at similar latencies from disparate sites on the leg, and
      capsaicin pretreatment of the skin did not increase the magnitude of these
      sensations. The pulsed and ramp-and-hold forms of stimulation were used in a
      paradigm designed to test for differential effects of systemic morphine on
      operant responses of non-human primates. Low doses of morphine reduced operant
      responding to pulsed thermal contact, while higher doses were required to affect
      responses to ramp-and-hold thermal stimulation. The low doses of morphine did not
      suppress non-nociceptive (intertrial) motor responses, indicating that motor
      inhibition was not responsible for the effects on escape responses to pulsed
      stimulation. Measurements of skin temperature 10 cm from the site of stimulation
      showed that morphine had no effect on baseline temperature but attenuated changes
      in skin temperature that were elicited by pulsed and by ramp-and-hold
      stimulation. This effect of morphine on skin temperature responses could not
      account for the reduction of operant responsivity to thermal stimulation. These
      results support previous findings that systemic morphine preferentially
      attenuates second pain sensations, and a new animal model of morphine-sensitive
      thermal nociception is established. These findings demonstrate the importance of
      defining the sources of afferent input and the response measures in experiments
      which attempt to measure antinociceptive effects of pharmacological agents.

PMID- 8880849
TI  - Individual differences in the hotplate test and effects of habituation on
      sensitivity to morphine.
AB  - Hotplate studies rarely match subjects into groups and often use high
      temperatures that are less sensitive to the effects of mild analgesics. Subjects
      may not be matched into groups because it has not been clearly demonstrated that
      there are reliable and robust individual differences in performance on the
      hotplate, and out of concern that the testing required to match subjects into
      groups might reduce the sensitivity of the task to mild analgesics by producing
      'behavioral tolerance'. Higher hotplate temperatures may be preferred because
      they reduce variability in response latencies, and it may be assumed that this
      precludes the need to match subjects into groups. The results of the present
      study demonstrate that there are reliable and robust differences among
      individuals tested on the hotplate, regardless of whether the hotplate is 50
      degrees C or 55 degrees C (alpha's > 0.90). The present results also confirm that
      lower hotplate temperatures are much more sensitive to the effects of mild
      analgesics: increased response latencies following a low dose of morphine (3
      mg/kg) could be reliably detected with only 8 rats at 50 degrees C, while the
      same dose would not be detected reliably at 55 degrees C unless more than 55 rats
      were tested. Finally, there was no evidence that habituation to the hotplate
      produced 'behavioral tolerance' or reduced the sensitivity of the test to the
      effects of morphine. These findings suggest that hotplate studies should match
      subjects into groups and use lower hotplate temperatures in order to increase the
      sensitivity of the test, but also out of an ethical obligation to minimize the
      intensity of the noxious stimulus and the number of animals exposed to it.

PMID- 8880850
TI  - The bee venom test: a new tonic-pain test.
AB  - The present study describes a new test of tonic pain to be used as an animal
      model of persistent pain. First, pain responses and edema produced by
      subcutaneous injection of increasing doses of honey bee venom into the hind paw
      of the rat were quantified. Second, the effect of morphine and aspirin on the
      pain responses was investigated. Finally, the response to concurrent injections
      of bee venom and formalin was examined. Subcutaneous injection of bee venom
      produced local inflammation, tonic-pain responses lasting from 10 min to more
      than 1 h, and marked edema lasting from 3 h to more than 48 h. Increasing doses
      of bee venom produced higher mean pain scores and increased durations of
      responding. The time course of the edema did not follow the time course of the
      pain responses. Analgesia was produced by morphine and aspirin, indicating that
      the bee venom test can be used to test analgesic drugs. Concurrent administration
      of bee venom and formalin produced pain responses similar to formalin alone, with
      a less profound interphase depression and a longer duration. The data suggest
      that the bee venom test is a valid animal model of experimental tonic pain.

PMID- 8880851
TI  - Treatment of a chronic allodynia-like response in spinally injured rats: effects
      of systemically administered excitatory amino acid receptor antagonists.
AB  - A chronic allodynia-like response to mechanical stimulation was observed in rats
      after severe spinal cord ischemia. This allodynia-like response was not relieved
      by most conventional analgesics used for treating chronic neuropathic pain. The
      present experiments evaluated the effects of systemically administered excitatory
      amino acid receptor antagonists, including the non-competitive N-methyl-D
      aspartate (NMDA) receptor/channel blockers MK-801 and dextromethorphan, the
      competitive NMDA receptor antagonist CGS 19755 and a competitive antagonist of
      the alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      NBQX, on the chronic allodynia-like response in spinally injured rats. Systemic
      MK-801, dextromethorphan and CGS 19755 dose-dependently relieved the mechanical
      allodynia-like response. Systemic MK-801 and CGS 19755, but not dextromethorphan,
      also induced severe motor impairment at analgesic doses. All three NMDA
      antagonists increased spontaneous motor activity. Systemic NBQX reduced muscle
      tone and caused sedation. The mechanical allodynia was only relieved by NBQX at a
      sedative dose. It is concluded that systemic NMDA, but not AMPA, receptor
      antagonists may have an analgesic effect upon the chronic allodynia-like
      response. However, the analgesic effect of all NMDA antagonists was associated
      with side effects. Dextromethorphan, which is clinically tolerated and produced
      less side effects, may be useful for treating chronic pain associated with
      central nervous system injury.

PMID- 8880852
TI  - Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic
      mechanisms. An experimental study in the mononeuropathic rat.
AB  - There is much evidence that tactile allodynia in rat models of mononeuropathy
      produced by sciatic nerve constriction is linked to disturbance of spinal
      GABAergic functions. Spinal cord stimulation (SCS) applied to such animals via
      chronically implanted electrodes may in some of the animals induce a significant
      increase of the withdrawal threshold in response to innocuous mechanical
      stimulation with von Frey filaments applied to the paw of the nerve ligated leg.
      The present study was performed in mononeuropathic animals with definite signs of
      tactile allodynia, which did not respond to SCS, GABA and the GABAB-agonist
      baclofen were administered intrathecally, in doses per se insufficient to
      influence the withdrawal thresholds, together with the previously ineffective
      SCS. This combination resulted in a marked and long-lasting increase of the
      thresholds. The GABAA-agonist muscimol given together with SCS also produced a
      similar, but less prominent threshold increase. The GABAB-antagonist 5
      aminovaleric acid (5-AVA) produced a transient suppression of the threshold
      increase induced by SCS together with either GABA or baclofen. In contrast, the
      GABAA-antagonist bicuculline had no apparent inhibitory effect on the threshold
      augmentation produced by SCS combined with GABA or baclofen. It is concluded that
      SCS may operate by upgrading the spinal GABAergic systems and that its potential
      for producing pain relief is dependent upon the availability of responsive GABA
      containing inhibitory interneurons. Moreover, it seems that the effects of SCS
      are more linked to the GABAB-than to the GABAA-receptor system.

PMID- 8880853
TI  - Behavioral and electrophysiological assessment of hyperalgesia and changes in
      dorsal horn responses following partial sciatic nerve ligation in rats.
AB  - Behavioral and electrophysiological methods were used to investigate the
      hyperalgesia and allodynia, and functional changes in lumbar spinal dorsal horn
      neurons, in a model of neuropathic pain (Selzer et al. 1990) involving ligation
      of one-third to one-half of one sciatic nerve in rats. One and 5 weeks following
      ligation, there was a significant reduction in hind limb withdrawal latency to
      noxious radiant heat on the operated side and, to a lesser degree, on the
      unoperated side. By 16 weeks, heat withdrawal latencies were reduced about
      equally (approximately 40%) on both sides. Withdrawal threshold to mechanical
      pressure was markedly reduced within 1 week on the operated side, and decreased
      in a time-dependent manner on the unoperated side. Heat withdrawal latency and
      von Frey withdrawal thresholds were not significantly affected in sham-operated
      rats. The same rats were tested in a paradigm measuring the isometric force of
      hind limb withdrawals elicited by graded noxious contact heat stimuli (38-52
      degrees C, 5 sec). Withdrawal force increased monotonically with stimulus
      temperature starting at a threshold of approximately 40 degrees C. Stimulus
      response functions were not significantly different between a sham-operated group
      and groups tested 5 (acute) and 16 weeks (chronic) after partial sciatic nerve
      ligation. Following behavioral testing, the animals were deeply anesthetized with
      pentobarbital sodium to allow electrophysiological recording of responses of
      single lumbar dorsal horn wide-dynamic range-type neurons to mechanical and
      noxious thermal stimulation of the hind paw. Recordings were made from 6 sham
      operated rats (26 neurons ipsilateral and 31 contralateral to the operated leg),
      from 7 rats receiving partial sciatic nerve ligation 5 weeks previously (29
      ipsilateral and 29 contralateral to ligation), and from 7 rats receiving partial
      sciatic ligation 16 weeks previously (18 ipsilateral, 29 contralateral to
      ligation). In several ligated rats we were unable to find heat-responsive neurons
      with cutaneous receptive fields on the hind paw ipsilateral to the ligation. For
      the neurons that were sensitive to heat, responses increased monotonically from a
      threshold of 40-42 degrees C. Neuronal stimulus-response functions for heat were
      not significantly different between ipsi- and contralateral (to operated) sides
      in the sham, 5-week or 16-week post-ligation groups, or between sham and 5- or 16
      week post-ligation groups. Mechanical receptive field areas were not
      significantly different between ipsi- and contralateral sides in the sham and 5
      week post-ligation groups, or between sham and 5-week post-ligation groups.
      However, receptive field areas were significantly larger in the 16-week post
      ligation group (both ipsi- and contralateral to ligation) compared to sham and 5
      week post-ligation groups. The results suggest that allodynia may be associated
      with a chronic enhancement of neuronal mechanosensitivity, but that the thermal
      hyperalgesia is not associated with enhanced neuronal responsiveness or force of
      withdrawal.

PMID- 8880854
TI  - Behavioral analysis of diffuse noxious inhibitory controls (DNIC):
      antinociception and escape reactions.
AB  - 'Diffuse noxious inhibitory controls' or DNIC is the inhibition of multireceptive
      neurons in the dorsal horn of the spinal cord that results when a noxious
      stimulus is applied to a region of the body remote from the neuron's excitatory
      receptive field. Although this phenomenon is well-documented, the behavioral
      consequences of DNIC are not clear. The present study was undertaken to determine
      how nocifensor withdrawal reflexes evoked by a noxious stimulus are altered by
      application of a second noxious stimulus to a distant part of the body. The tail
      flick or hindpaw withdrawal reflex of lightly anesthetized (0.6-1.0% halothane)
      rats was measured before, during and after another appendage was placed in water
      ranging in temperature from 45 to 54 degrees C. When the forepaw or hindpaw was
      placed in water exceeding 49 degrees C the tail flick reflex to acute noxious
      radiant heat was inhibited. In contrast, noxious conditioning stimuli, regardless
      of temperature or location, had no effect on the latency for hindpaw withdrawal
      evoked by an acute noxious stimulus, but did produce a change in reflex
      topography from flexion to extension. These results, along with previous research
      on DNIC, suggest that intense noxious stimuli: (1) inhibit the tail flick reflex
      via inhibition of multireceptive neurons in the dorsal horn; (2) disinhibit
      hindpaw extensor motoneurons by inhibiting the activity of multireceptive neurons
      involved in hindlimb flexion; and (3) reduce pain sensation by inhibiting
      multireceptive neurons projecting to the brain (see Model in Discussion).

PMID- 8880855
TI  - Treatment of a chronic allodynia-like response in spinally injured rats: effects
      of systemically administered nitric oxide synthase inhibitors.
AB  - We have previously reported that we have observed chronic pain-like response to
      light mechanical stimuli (allodynia) in rats after severe spinal cord ischemia,
      which resembles some painful conditions in chronic spinally injured patients and
      is not relieved by a number of conventional analgesics used for treating chronic
      neuropathic pain. In the present study, we tested the effects of the non
      selective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester
      (L-NAME) and the selective neuronal NOS inhibitor 7-nitro indazole (7-NI) and 6
      nitro indazole (6-NI) on the chronic allodynia-like behavior. Systemic L-NAME
      dose-dependently relieved mechanical allodynia-like response in a stereo-specific
      and L-arginine-reversible manner without causing sedation or motor deficits.
      However, L-NAME significantly elevated systemic blood pressure. Systemic 7-NI
      relieved chronic allodynia in a L-arginine reversible manner, did not increase
      blood pressure or induce sedation, but caused motor deficits at a high dose,
      which was not reversed by L-arginine. Systemic 6-NI also relieved the chronic
      allodynia, which was however associated with severe sedation. In order to exclude
      the possibility that the effect of L-NAME on blood pressure was involved in the
      analgesic effect observed, the effect of systemically applied adrenaline was
      examined. Adrenaline increased the systemic blood pressure to a similar extent as
      L-NAME, but did not relieve allodynia. It is suggested that blockade of NOS by L
      NAME relieved the chronic allodynia-like behavior in spinally injured rats. This
      effect was likely to be mediated by a blockade of neuronal isoforms of NOS, as 7
      NI relieved the allodynia in a L-arginine-reversible manner. Consequently,
      generation of NO by neuronal NOS may be critically involved in the maintenance of
      this abnormal pain-related sensation. The possibility of using NOS inhibitors as
      potential novel analgesics is discussed.

PMID- 8880856
TI  - Strychnine-sensitive modulation is selective for non-noxious somatosensory input
      in the spinal cord of the rat.
AB  - Touch-evoked allodynia, an important symptom of clinical neural injury pain, can
      be modelled acutely and reversibly in the urethane-anesthetized rat using
      intrathecal (i.t.) strychnine (STR). Allodynia, after i.t. STR (40 micrograms),
      is manifest as a significant enhancement of cardiovascular and motor responses
      evoked by normally innocuous brushing of the hair (hair deflection), as compared
      to responses evoked by either hair deflection after i.t. saline (SAL), or to i.t.
      STR (40 micrograms) with no tactile stimulus. The present study investigated: (1)
      the pharmacology of afferent neural inputs involved in STR-dependent allodynia
      using neonatal capsaicin and the non-NMDA receptor antagonist 2,3-dihydroxy-6
      nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX); and (2) the effect of i.t. STR on
      responses evoked by peripheral noxious stimulation. Neonatal capsaicin (25 mg/kg,
      s.c., post-natal day (PND) 1, and 50 mg/kg, s.c., PND 2, 3, 4, 11, 25, 55 and 85)
      significantly attenuated the responses evoked by noxious mechanical, thermal or
      chemical stimuli, but had no effect on STR-dependent allodynia. All hair
      deflection-evoked, STR-dependent responses were dose-dependently inhibited by
      i.t. NBQX. The ED50 values and 95% confidence intervals were 10.4 micrograms (5.5
      19.6) for the motor withdrawal response, 14.4 micrograms (8.6-24.0) for changes
      in MAP and 12.2 micrograms (6.8-21.8) for changes in HR. Cortical EEG synchrony
      was unchanged by i.t. NBQX confirming its spinal locus of action. Intrathecal STR
      neither reduced nor enhanced the responses elicited by noxious stimuli in
      capsaicin- or vehicle-pretreated rats. These results indicate that STR-dependent
      allodynia is initiated by primary afferents not normally involved in nociception
      (possibly A beta-fibers), and that STR-sensitive modulation in the spinal cord is
      selective for non-noxious sensory input. The sensitivity of STR-dependent
      allodynia to non-NMDA receptor antagonists, and the failure of i.t. STR to
      produce hyperalgesia to mechanical, thermal or chemical noxious stimuli, confirm
      the independence of nociceptive pathways and STR-sensitive afferent inputs in
      this model.

PMID- 8880857
TI  - A nitric oxide synthesis inhibitor (L-NAME) reduces licking behavior and Fos
      labeling in the spinal cord of rats during formalin-induced inflammation.
AB  - Formalin injected subcutaneously into the hindpaw of the rat produces an animal
      model of inflammation that exhibits a phasic component and a tonic component of
      pain. We evaluated the effects of a nitric oxide synthase inhibitor, N omega
      nitro-L-arginine methyl ester (L-NAME), on a formalin-induced behavior, hindpaw
      licking, and on Fos-labeling of nuclei in the fifth lumbar spinal segment. Our
      results demonstrated that pretreatment with intrathecal doses of 0.3 and 1.0 mg
      of L-NAME significantly reduced licking behavior associated with injection of
      formalin into the left hindpaw of the rat. In addition, these same doses of L
      NAME reduced formalin-induced Fos-labeling in the ipsilateral dorsal gray matter
      (as compared to the contralateral gray matter). Qualitative assessment suggested
      that the reduction in labeling occurred primarily in the superficial dorsal horn.
      The stereoisomer, D-NAME, administered at the same doses had little to no effect
      on either formalin-induced licking or Fos-labeling. Finally, our results revealed
      that total licking time was related to Fos-labeling. Rats that spent less time
      licking the hindpaw exhibited a smaller increase in Fos-labeling. Our results
      suggest that the production of nitric oxide is associated with licking behavior
      resulting from formalin injection into the hindpaw of rats. Our results also
      suggest that the production of nitric oxide and Fos are associated. Indeed, these
      substances may be involved in spinal pathways associated with nociception.

PMID- 8880859
TI  - Calcitonin gene-related peptide content, basal outflow and electrically-evoked
      release from monoarthritic rat spinal cord in vitro.
AB  - In this study, Freund's adjuvant-induced monoarthritis in the rat hind paw was
      used to induce chronic pain and inflammation. In order to compare the basal
      outflow, electrically-evoked release and total content of calcitonin gene-related
      peptide like immunoreactivity (CGRP-LI) with previously reported changes in
      substance P (SP-LI), the lumbar enlargement of monoarthitic (complete Freund's
      adjuvant-treated, CFA rat) and control (incomplete Freund's adjuvant-treated, IFA
      rat) spinal cords were used. During the 4-wk period after injection, neither the
      basal nor the evoked release of CGRP-LI from CFA cords differed from controls. By
      contrast, we have previously reported that SP-LI release from CFA rat spinal
      cords was significantly higher than from controls, 21 days after inoculation with
      Freund's adjuvant. Electrically-evoked CGRP-LI release from 21-day CFA rat spinal
      cord slices was not modified by superfusion with a GABAB antagonist, CGP 36742
      (100 microM) which could greatly increase SP-LI release. However, the release of
      both peptides was significantly increased to the same extent in IFA and normal
      tissue but to a lesser extent in CFA cords, by superfusion with the opioid
      antagonist naloxone (1 microM). In conclusion, CGRP-LI, unlike SP-LI, did not
      appear to be susceptible to any changes in the lumbar enlargement of the rat
      spinal cord during inflammation of the hind paw. In addition, CGRP-LI release was
      increased by antagonism of opiate but not GABAB receptors, suggesting that during
      chronic inflammation of one hind paw, the GABAB ergic system, unlike the opioid
      system, might be activated to selectively inhibit the enhanced SP-LI release but
      not CGRP-LI release which is not changed.

PMID- 8880858
TI  - The NMDA receptor antagonist MK-801 differentially modulates mu and kappa opioid
      actions in spinal cord in vitro.
AB  - We have examined the interactions between NMDA receptors and opioid effects in
      isolated neonatal rat spinal cord. Electrical stimulation of a lumbar dorsal root
      evoked a nociceptive-related slow ventral root potential (sVRP) recorded at the
      corresponding ipsilateral ventral root. The kappa opiate receptor agonist U69,593
      (2.5 nM-1 microM) depressed sVRP area by a maximum of 80%, EC50 was approximately
      33 nM. Both the non-specific antagonist naloxone and the kappa-specific
      antagonist nor-binaltorphimine (nor-BNI) antagonized the effects of U69,593.
      Morphine, a mu agonist, (1 nM-1 microM) depressed sVRP area with an approximate
      EC50 of 90 nM. The effects of both mu and kappa opioid agonists were selective
      for the very slow metabotropically mediated components of the sVRP, compared to
      the relatively fast NMDA receptor-mediated components. The non-competitive N
      methyl-D-aspartate (NMDA) antagonist MK-801 (20 nM) had no effect on sVRP area
      when applied alone but co-applied with morphine significantly potentiated the
      depressant effects of morphine. In contrast, MK-801 either had no effect on or
      slightly antagonized the depressant effects of U69,593. Naloxone following
      morphine produced a significant increase in sVRP area above pre-morphine control
      values; the increase lasted 30 min or more. Neither naloxone nor nor-BNI was
      associated with an increase in sVRP area when given alone or following U69,593.
      MK-801 co-applied with morphine blocked the rebound increase in sVRP area
      following naloxone. These results suggest that (1) both mu and kappa receptor
      agonists exert similar selective depressant effects on spinal nociceptive
      neurotransmission; (2) mu but not kappa agonists exert prolonged excitatory
      effects that oppose the depression; and (3) NMDA receptors play a role in
      determining opioid analgesic potency and naloxone-precipitated
      hyperresponsiveness. The results may be related to initial steps in the
      development of acute tolerance to mu opioids, and suggest that tolerance to kappa
      opioids may have a different mechanism.

PMID- 8880860
TI  - Characteristics of nerve growth factor induced hyperalgesia in adult rats:
      dependence on enhanced bradykinin-1 receptor activity but not neurokinin-1
      receptor activation.
AB  - Treatment of adult rats with a single dose of nerve growth factor (NGF, 1 mg/kg,
      i.p.) results in a prolonged hypersensitivity to noxious thermal stimulation
      which becomes noticeable within 30 min of administration and lasts for several
      days. A significant mechanical hyperalgesia develops within 7 h following
      injection of NGF and persists for up to 7 days. In the present set of experiments
      we describe certain quantitative features of this hyperalgesia. The initial
      thermal hyperalgesia can be highly variable and is associated to some degree with
      the presence of an overt immunologic reaction. The mechanical hyperalgesia is
      reproducible enough to reveal a clear dependency on the dose of NGF. We also
      examined the pharmacological properties of the NGF-induced hyperalgesia. The
      bradykinin BK1 receptor antagonist des-Arg9[Leu8]BK transiently blocked the
      thermal hyperalgesia when injected 1 day after NGF administration whereas
      mechanical thresholds were further reduced under this protocol. The BK2
      antagonist HOE 140 had no effect on this late NGF-induced hyperalgesia. Injection
      of the neurokinin NK1 receptor antagonist CP-96345 or its inactive enantiomer CP
      96344 one day after NGF both induced a transient block of NGF-induced thermal
      hyperalgesia indicating a non-specific effect rather than an action at NK1
      receptors. This was confirmed by finding no reversal of NGF-induced hyperalgesia
      by RP67580, another NK1 receptor blocker. These results suggest upregulation and
      activation of BK1 but not NK1 receptors as an additional, probably peripheral,
      mechanism for the late phase of NGF-induced thermal hyperalgesia.

PMID- 8880861
TI  - Endotoxin-induced local inflammation and hyperalgesia in rats and mice: a new
      model for inflammatory pain.
AB  - Lipopolysaccharide, also known as endotoxin (ET), is a major constituent of the
      outer membrane of the cell wall of most gram negative bacteria. ET is known to
      cause a number of pathophysiological changes associated with illness including
      inflammatory pain. The aim of this study is to characterize the peripheral
      hyperalgesia induced by ET in rats and mice. Different groups of rats and mice
      received different doses of ET ranging from 0.6 microgram to 40 micrograms
      dissolved in 50 microliters saline and injected in the plantar area of the left
      hind legs. All animals were subjected to tail immersion (TF), hot plate (HP) and
      paw pressure (PP) tests, 2-3 days prior to ET injection and during the following
      1-2 days. ET injections produced a dose-dependent decrease in the latencies of
      the HP and PP tests of the injected leg reaching a maximum decrease of 50-60% of
      the control with 20-40 micrograms ET at 9 h (rats) and 24 h (mice) after the
      injection. Almost complete recovery was observed after 24 h in rats and 48 h in
      mice. TF latencies showed a less but a significant decrease while PP of the
      opposite leg and all tests in saline-injected animals did not elicit significant
      variations and served as additional controls. Our results indicate that the use
      of ET-produced hyperalgesia is a valid model for local and reversible
      inflammatory pain, with minimal distress to the animal. This model can also be
      used to study the efficacy of various anti-inflammatory and analgesic drugs and
      the molecular mechanisms of inflammation induced by bacterial invasion.

PMID- 8880862
TI  - Pain memories in phantom limbs: a case study.
AB  - Pain experienced in a limb prior to amputation may influence the course of
      phantom limb pain many months later. Katz and Melzack (1990) found that 42% of
      their sample reported a 'somatosensory pain memory' which resembled the quality
      and location of a painful, or non-painful pre-amputation sensation. For many
      amputees, pain memories are vivid experiences which incorporate both emotional
      and sensory aspects of the pre-amputation pain (Katz 1992). Katz and Melzack
      (1990) suggest that sensory input will 'trigger' somatosensory pain memories
      while the affective component of a pain memory is generated by the intensity,
      quality and location of the current experience of phantom limb pain. The present
      case study used a diary design to examine whether 'triggers' could be identified
      for somatosensory pain memories. Over a 9-month period, the patient reported
      daily experience of ongoing phantom limb pain, generally confined to the distal
      part of the limb, and 5 episodes of injury-related phantom limb pain, primarily
      experienced in the calf of the missing limb. A 'trigger' was identified for each
      of the episodes of injury-related phantom limb pain, and a significant finding in
      this study was that two episodes of injury-related phantom limb pain were
      associated with cognitive and/or emotional, rather than sensory 'triggers'.

PMID- 8880863
TI  - Psychosomatic treatment of phantom limb pain with post-traumatic stress disorder:
      a case report.
AB  - The successful treatment of severe left lower limb phantom pain is reported.
      Hypnosis and antidepressant drugs were the basis for the treatment which
      controlled the phantom limb pain and an associated post-traumatic stress
      disorder.

PMID- 8880864
TI  - Analgesic effect of subarachnoid neostigmine in two patients with cancer pain.
AB  - Two patients suffering with severe pain due to metastatic abdominal neoplasm were
      selected to examine whether subarachnoid neostigmine provided effective pain
      relief. Neostigmine was injected through a catheter introduced into the
      subarachnoid space at L4-L5. Patients were monitored for changes in arterial
      blood pressure, cardiac and respiratory rates, body temperature, level of
      consciousness and neurologic change. Pain was classified by the patients on a
      verbal four-grade scale, and analgesia was classified on a verbal three-grade
      scale. Complete pain relief was obtained 2 h after neostigmine (0.2 mg) in one
      patient and 4 h after neostigmine (0.1 mg) in the second patient. Pain of mild
      intensity returned 20 and 22 h after drug administration, respectively.
      Gastrointestinal discomfort was observed in both cases, but nausea and vomiting
      occurred only in the patient treated with the highest dose of neostigmine. No
      significant change in the monitored parameters was observed, except for a 6-h
      period of decreased blood pressure in the patient treated with the lower dose of
      neostigmine which required no specific treatment. The results obtained in these
      anecdotal cases indicate that subarachnoid neostigmine may provide analgesia in
      patients with pain arising from neoplasia, but further studies using controlled
      trials are needed before the drug is brought into clinical use.

PMID- 8880865
TI  - Neurofibromatosis and associated tumour suppressor genes.
AB  - Neurofibromatosis 1 and 2 (NF1 and NF2) are autosomal dominantly inherited
      disorders with close to 100% penetrance. NF1 is one of the most frequent human
      genetic diseases with an incidence of 1:3000. The incidence of NF2 is about 10
      fold lower. NF1 is caused by mutations which inactivate the NF1 gene on
      chromosome 17q, while the NF2 gene is on chromsome 22. Both genes are tumour
      suppressor genes. The product of the NF1 gene, called neurofibromin, is a large
      protein of 2818 amino acids. The protein acts as a negative regulator in the ras
      signal transduction pathway and may also act downstream of ras. In the cell types
      that are affected in NF1 patients, the absence of neurofibromin leads to
      increased proliferation resulting in benign, and in some cases malignant tumours.
      The product of the NF2 gene is a protein of 595 amino acids. The protein displays
      in its N-terminal half considerable homology with proteins that are involved in
      contacts between the cytoskeleton and the cell membrane, and a similar function
      has been proposed for the NF2 protein. How the absence of the NF2 protein may
      lead to the development of Schwannomas and meningiomas, which are the major
      manifestations of NF2 in patients, is not clear at present.

PMID- 8880866
TI  - p21ras in carcinogenesis.
AB  - The activation of p21ras proteins is required in signal transduction pathways
      that lead to cell proliferation. More recently, a role for p21ras proteins has
      also been suggested in pathways to apoptosis and in the regulation of the cell
      cycle. Pointmutated p21ras oncogenes code for constitutively activated p21ras
      proteins, which disturb the balance between cell growth and cell death in favour
      of cell growth. In this way, p21ras oncoproteins may contribute to
      carcinogenesis. The binding of growth factors to their receptors triggers a
      cascade of protein interactions, including activation of the p21ras proteins. In
      turn, p21ras proteins set the machinery for cell division in motion by
      stimulating different effector proteins which regulate the morphological
      alterations, the nutritional requirements, and the changes in gene expression
      necessary for cell division. The presence of p21ras oncoproteins constitutively
      stimulate proliferation, whilst the apoptotic pathway is suppressed along with
      the loss of cell cycle regulation. This review describes the function of the
      p21ras proteins in signal transduction pathways that control proliferation and
      apoptosis, and regulate the cell cycle. The dysregulation of these signal
      transduction pathways due to the presence of p21ras oncoproteins is discussed in
      the context of early carcinogenesis.

PMID- 8880868
TI  - Apoptosis: pathophysiology of programmed cell death.
AB  - In all normal tissues, cell proliferation and cell death are balanced. The
      physiology of normal cell death, which has become generally known as apoptosis or
      programmed cell death, has been intensely investigated in recent years. In this
      review the cell biology and biochemistry of apoptosis are discussed. Although
      apoptotic cells can be morphologically recognized, characteristic molecular
      features such as internucleosomal DNA fragmentation, and histochemical techniques
      such as in situ end labeling, facilitate the recognition of apoptosis. Many of
      the genes involved in the regulation of apoptosis, which include cell growth
      associated genes such as c-myc and p53, have been identified. It has become clear
      that the bcl-genes (more explicitly bcl-2 and bax) are important apoptosis
      regulators. The details of the mechanism of programmed cell death are, however,
      not completely unraveled. It has become clear that apoptosis plays an important
      role in organ and tissue development during embryogenesis. Examples are the
      morphogenesis of limbs from limb buds, the development of the central nervous
      system and the maturation of the hematopoietic and lymphatic systems. Hormonal
      regulation of cells and tissues is also partly executed through apoptosis. In a
      variety of disease apoptosis plays a role. In cancer, apoptosis is a crucial
      feature, and in the resolution of inflammatory reactions, apoptosis is essential.
      In neurodegenerative diseases, dysregulation of the cell death programme may play
      a role. Further elucidation of the role of apoptosis in these diseases may lead
      to new possibilities for treatment.

PMID- 8880867
TI  - The role of p53 in cell cycle regulation.
AB  - The tumor suppressor gene p53, implicated in diverse types of human tumors,
      functions both as a gene-specific transcription factor as well as a specific
      inhibitor of the transcription of certain genes. The two physiological outcomes
      of re-expression of wild type p53 in tumor cells, not expressing wild type p53,
      are G1 arrest and apoptosis. The mechanism of G1 arrest by p53 is much better
      documented than its ability to trigger apoptosis. P53 as a transcription factor
      induces the expression of p21WAF1/CIP1/Sdi1, an inhibitor of the cyclin dependent
      kinases (CDKs)2, 3, 4 and 6. Thus, a G1 arrest can result simply by the p53
      induced expression of p21WAF1/CIP1/Sdi1. Amongst the other genes presently
      characterized to be regulated by p53 are BAX, a homologue of the BCL-2 gene. Bax
      does not trigger apoptosis, but simply accelerates the rate at which apoptosis
      proceeds54. P53 also down regulates the expression of cyclin A, providing a
      secondary break on cell cycle progression into the through the S phase.

PMID- 8880869
TI  - Genes responsible for familial breast cancer.
AB  - A family history for breast cancer appears to be a major risk factor for breast
      cancer. It has been estimated that 5% of all breast cancers are hereditary. In
      the last five years much progress has been made in the identification of genes
      responsible for breast cancer. Much interest is focused on the BRCA-1 gene, which
      is associated with early onset breast and ovarian cancers. Heterogeneity within
      and across families in the pattern of cancer susceptibility has suggested that
      different susceptibility alleles may exist. The BRCA-1 gene has been cloned but
      the function of its product has not been determined. BRCA-1 mutations seem not to
      be involved in sporadic breast cancer. A second breast cancer susceptibility
      gene, BRCA-2, has been localized to chromosome 13q12-q13 but has not been
      identified as yet. Loss of heterozygosity of 13q is observed in 25% of sporadic
      breast tumors, which indicates that BRCA-2 might be a tumor suppressor gene. BRCA
      2 confers only a low ovarian cancer risk. The TP53 gene has also been associated
      with breast cancer but to a much more limited extent than BRCA-1. Germline TP53
      mutations have been found in patients with familial breast cancer. Other genes
      that have been associated with breast cancer risk are the androgen receptor (AR)
      gene and the ataxia teleangiectasia (AT) gene. The importance of the AR gene
      appears to be limited but the AT gene might be of considerable importance. It is
      to be expected that additional breast cancer susceptibility genes will be
      identified in the near future.

PMID- 8880870
TI  - Regulation of the invasion suppressor function of the cadherin/catenin complex.
AB  - Invasion is the cause of cancer malignancy. Invasion results from the cross-talk
      between cancer cells and host cells, building molecular invasion-promoter and
      invasion-suppressor complexes. The E-cadherin/catenin invasion-suppressor complex
      is regulated multifactorially, at multiple levels and sometimes in a reversible
      way. Mutations in the E-cadherin gene combined with loss of the wild type allele,
      causing irreversible downregulation, has been demonstrated only in a minority of
      human cancers. Posttranslational and reversible downregulation has been ascribed
      to tyrosine phosphorylation of beta-catenin. Phosphorylation is also implicated
      in transmembrane receptor signal transduction through the E-cadherin/catenin
      complex. E-cadherin interacts with E-cadherin on another cell through a dimeric
      adhesion zipper, involving the histidine-alanine-valine (HAV) sequence of the
      first extracellular domains. This is the major extracellular like of the E
      cadherin/catenin complex, though not the only one. Intracellularly, the list of
      proteins that bind to or signal through the complex or through one or more of its
      elements is steadily growing. Extrinsic factors may influence the complex. At
      least in vitro, insulin-like growth factor-I, retinoic acid, tangeretin and
      tamoxifen were shown to upregulate the functions of the E-cadherin/catenin
      complex including inhibition of invasion.

PMID- 8880871
TI  - The cellular derivation and the life span of the myofibroblast.
AB  - The presence of myofibroblasts in granulation tissue and various fibrotic
      settings is well established. Recent work on this cell has shown that
      myofibroblasts derive mainly from local fibroblasts, but also from pericytes and
      smooth muscle cells as well as from specialized cells such as perisinusoidal
      stellate cells of the liver and mesangial cells of the kidney glomerulus. During
      the healing of an open wound, myofibroblasts disappear by means of apoptosis when
      the wound is closed and granulation tissue gradually transforms into scar tissue.
      The possibility exists that an altered regulation of this process leads to the
      development of a hypertrophic scar.

PMID- 8880872
TI  - Role of stromal myofibroblasts infiltrating colon cancer in tumor invasion.
AB  - In the normal colon, myofibroblasts are closely apposed to colonocytes where they
      deposit type IV collagen, the main basement membrane component. In colon
      carcinomas, this epithelial-mesenchymal association is physically disrupted,
      leading to the production of an abnormal, type IV collagen defective, basement
      membrane. Tumor-infiltrating myofibroblasts are migratory cells that accumulate
      at the invasive front of the colorectal carcinomas. They produce lytic enzymes
      able to degrade the basement membrane surrounding tumor glands. They also
      participate in the synthesis of the extracellular matrix components of the tumor
      stroma, which could subsequently alter the adhesive and migratory properties of
      the epithelial colon cancer cells. These results suggest that tumor-infiltrating
      myofibroblasts play a role in the invasion and metastasis of colorectal tumor
      cells.

PMID- 8880873
TI  - The plasminogen activation system in tumour invasion and metastasis.
AB  - The involvement of proteases in the metastatic spread of tumour cells and in
      tumour related processes, such as angiogenesis and ulceration, has been known for
      many decades. This chapter reviews the involvement of one proteolytic system--the
      plasminogen activation system--in tumour progression. In recent years, many
      biochemical properties of the various components of the plasminogen activation
      system have become known. These properties and the functional relationship
      between the components are discussed in the first section. Since interfering with
      proteolysis by tumour cells and by newly formed endothelial cells can be an
      objective for future therapy, experimental tumour models have been used to study
      the effects of inhibitors of plasminogen activation. The second section deals
      with this issue. Finally, the presence of the various components of the
      plasminogen activation system in human tumours is reviewed. Following the
      availability of specific ELISAs, antibodies and molecular probes, the content and
      the cellular distribution of the components of the plasminogen activation system
      have recently been mapped in various human tumours.

PMID- 8880874
TI  - Hematopoietic growth factors in leukemia.
AB  - The responses of leukemic cells to recombinant hematopoietic growth factors
      (HGFs) have been extensively studied, both in vitro and in vivo. Here, we
      summarize the current knowledge of the role that HGFs and growth modulatory
      cytokines play in the growth of leukemia. Particular attention is paid to the
      proliferation and maturation abilities of acute myeloblastic leukemia (AML), and
      the role HGFs play in these processes. The HGF responses of leukemic cells are
      discussed in the context of autocrine growth mechanisms, (cyto-)genetic
      abnormalities and defective function of HGF receptors. These studies have
      contributed considerably to our insight into the heterogeneous pathophysiology of
      leukemia.

PMID- 8880875
TI  - Genetic mechanisms of estrogen-independence in breast cancer.
AB  - Endocrine therapy is effective in the treatment of breast cancer. Adjuvant
      treatment with tamoxifen reduces tumor recurrence and achieves increased
      survival. In metastatic disease, tamoxifen treatment accomplishes objective
      responses in +/- 50% of the patients with estrogen receptor-positive primary
      tumors. However, the response duration is limited due to the inevitable
      development of metastases resistant to tamoxifen. The mechanisms leading to
      tamoxifen resistance are largely unknown. We have set out to identify genetic
      pathways in the tumor cells causing failure of tamoxifen therapy. We selected an
      estrogen-dependent human breast cancer cell line (ZR-75-1) and demonstrated that
      genetic and epigenetic alterations can change the hormone-response phenotype of
      these cells. Subsequently, we applied insertional mutagenesis with defective
      retroviruses to these ZR-75-1 breast cancer cells. Integration of a retrovirus in
      the cellular DNA alters the genome structure and may modify the expression of
      genes in its surroundings. As a result of the altered gene expression, the
      biological phenotype of the infected cell may be changed. The infected ZR-75-1
      cells were subjected to tamoxifen selection and a panel of tamoxifen-resistant
      cell lines has been established. Screening for a common integration site for the
      retrovirus has provided, so far, compelling evidence for the involvement of at
      least one genetic locus (BCAR 1) in breast cancer antiestrogen resistance in
      vitro.

PMID- 8880876
TI  - The androgen receptor in prostate cancer.
AB  - The androgen receptor is a member of the family of nuclear receptors. In its
      activated form as an androgen receptor ligand complex (the ligand can either be
      testosterone or 5a-dihydrotestosterone), the androgen receptor is able to
      regulate a specific expression of target genes. The androgen receptor is
      expressed at high levels in male reproductive tissues. Mutations in the androgen
      receptor gene are the molecular cause of the androgen insensitivity syndrome,
      which is characterized by an aberrant male or an apparently female phenotype.
      Expansion of a CAG-repeat, encoding a polymorphic glutamine stretch is the cause
      of a rare motor neuron disease (Kennedy's disease). Hormonal therapy is the
      treatment of choice for metastatic prostate cancer. Hormone refractory prostate
      tumors in general still express androgen receptor. In a proportion of the late
      stage prostate tumors, somatic mutations in the androgen receptor gene have been
      described. Mutations can result in diminished ligand specificity of the androgen
      receptor. Furthermore, it has been hypothesized that ligand independent
      mechanisms can also be involved in androgen receptor activation.

PMID- 8880877
TI  - Rational design for the development of epidermal growth factor receptor
      antagonists.
AB  - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha)
      bind with similar high affinity to the human EGF receptor. Using a domain
      exchange strategy we have shown that the C-terminal linear region of these
      molecules is involved in high affinity receptor binding. By further single amino
      acid substitution in this linear C-terminal region, a putative interaction site
      of these ligands with their receptor has been identified. This identification of
      a receptor binding domain in EGF/TGF alpha provides an important initial step in
      the development of EGF receptor antagonists with significant clinical potential.

PMID- 8880878
TI  - Molecular mechanisms of multidrug resistance in cancer chemotherapy.
AB  - The occurrence of multidrug resistance (MDR) is one of the main obstacles in the
      successful chemotherapeutic treatment of cancer. MDR cell lines are resistant to
      the so-called naturally occurring anti-cancer drugs, such as anthracyclines,
      Vinca alkaloids and epipodophyllotoxins, but are not cross-resistant to
      alkylating agents, antimetabolites and cisplatin. So far, three separate forms of
      MDR have been characterized in more detail: classical MDR, non-Pgp MDR and
      atypical MDR. Although all three MDR phenotypes have much in common with respect
      to cross-resistance patterns, the underlying mechanisms certainly differ.
      Atypical MDR is associated with quantitative and qualitative alterations in
      topoisomerase II alpha, a nuclear enzyme that actively participates in the lethal
      action of cytotoxic drugs. Atypical MDR cells do not overexpress P-glycoprotein,
      and are unaltered in their ability to accumulate drugs. In this review we will
      focus on classical and non-Pgp MDR. The molecular mechanism of classical and non
      Pgp MDR is transcriptional activation of membrane-bound transport proteins. These
      transport proteins belong to the ATP-binding cassette (ABC) superfamily of
      transport systems. The classical MDR phenotype is characterized by a reduced
      ability to accumulate drugs, due to activity of an energy-dependent uni
      directional, membrane-bound, drug-efflux pump with broad substrate specificity.
      The classical MDR drug pump is composed of a transmembrane glycoprotein (P-glyco
      protein-Pgp) with a molecular weight of 170 kD, and is, in man, encoded by the so
      called multidrug resistance (MDR1) gene. Typically, non-Pgp MDR has no P-gly
      coprotein expression, yet has about the same cross-resistance pattern as
      classical MDR. This non-Pgp MDR phenotype is caused by overexpression of the
      multidrug resistance-associated protein (MRP) gene, which encodes a 190 kD
      membrane-bound glycoprotein (MRP). MRP probably works by direct extrusion of
      cytotoxic drugs from the cell and/or by mediating sequestration of the drugs into
      intracellular compartments, both leading to a reduction in effective
      intracellular drug concentrations. For the classical MDR phenotype, evidence is
      accumulating that it plays a role indeed, in clinical drug resistance, especially
      in some hematological malignancies (acute myeloid leukemia, multiple myeloma and
      non-Hodgkin's lymphoma) and solid tumors (soft tissue sarcomas and
      neuroblastoma). The association of MRP with clinical drug resistance has not been
      elaborated, yet, and studies on MRP expression in human cancer have just begun.
      We found that overexpression of MRP, as determined by RNase protection assay as
      well as by immunohistochemistry, occurs in several human cancers, among which are
      cancer of the lung, esophagus, breast and ovary, and leukemias. Further studies
      are indicated to establish whether elevated MRP expression at diagnosis is an
      unfavorable prognostic factor for clinical outcome of chemotherapy.

PMID- 8880879
TI  - A pediatrician's view. More rifle, less shotgun.

PMID- 8880880
TI  - Emerging diarrheal pathogens: Cryptosporidium parvum, Isospora belli, Cyclospora
      species, and microsporidia.

PMID- 8880881
TI  - Helicobacter pylori infection.

PMID- 8880882
TI  - Hepatitis C infections.

PMID- 8880883
TI  - Infections due to drug-resistant pneumococci, enterococci, and Mycobacterium
      tuberculosis.

PMID- 8880884
TI  - Emerging and newly identified viral infections.

PMID- 8880885
TI  - Cat-scratch disease and Bartonella henselae infections in children.

PMID- 8880886
TI  - The use of alpha-adrenoceptor antagonists in the pharmacological management of
      benign prostatic hypertrophy: an overview.
AB  - Benign prostatic hypertrophy (BPH) produces symptomatic urethral obstruction in a
      significant percentage of older men. Since the incidence of BPH is age related,
      the clinical and economic impact of this disease will continue to progress as
      average lifespan increases. BPH is associated with growth of both glandular and
      stromal elements of the prostate gland. Glandular hyperplasia can be partially
      reversed by withdrawal of androgenic tone with androgen receptor antagonists or
      steroid-5-alpha-reductase inhibitors. However, the reduction in prostatic size
      produced by these agents has little effect on the dynamic tone induced by nerve
      mediated contraction of stromal smooth muscle. This tone is mediated by
      activation of alpha-adrenoceptors. Therefore the alpha-adrenoceptor antagonists
      represent a useful pharmacological approach to the treatment of BPH. Studies in
      isolated strips of human prostate show that either exogenous alpha-adrenoceptor
      agonists or electrical field stimulation will induce contraction. Studies with
      selective antagonists such as prazosin show that this response is mediated by the
      alpha 1-adrenoceptor, even though radioligand binding studies show the presence
      of alpha 1 and alpha 2 adrenoceptor subtypes in approximately equal density.
      Following the cloning of multiple alpha 1-adrenoceptors, the contractile response
      in human prostate has been assigned to the alpha 1A adrenoceptor. However, recent
      data would suggest a functional role for another subtype, which has not yet been
      cloned, and designated as alpha 1L based on a relatively low affinity for
      prazosin. Clinical trials have shown efficacy of a variety of alpha-adrenoceptor
      antagonists in BPH, including non-selective agents such as phenoxybenzamine, as
      well as a variety of selective alpha 1-adrenoceptor antagonists, most
      structurally related to prazosin. The agents most commonly employed at the
      present time include the prazosin analogs terazosin, doxazosin and alfuzosin, as
      well as the structurally unrelated indoramin and tamsulosin. The design of new
      alpha 1-antagonists for BPH has concentrated on agents producing preferential
      blockage of urogenital vis-a-vis vascular alpha 1-adrenoceptors, based either on
      selectivity for the alpha 1A-adrenoceptor subtype or on functional uroselectivity
      in animal models. While these newer agents offer the prospect of reducing the
      incidence of the cardiovascular side effects associated with current therapy
      their superiority over nonselective alpha 1-adrenoceptor antagonists remains to
      be demonstrated in the clinical setting.

PMID- 8880887
TI  - Tachykinins in the autonomic nervous system.

PMID- 8880888
TI  - Inhibition of sympathetic noradrenergic transmission by guanabenz and
      guanethidine in rat isolated mesenteric artery: involvement of neuronal potassium
      channels.
AB  - The present study investigated the effects of the alpha 2-adrenoceptor agonist
      guanabenz and the adrenergic neurone blocking drug guanethidine on the resting
      and stimulation-induced (S-I) effluxes of radioactivity from rat isolated
      mesenteric artery preparations in which the noradrenergic transmitter stores had
      been radiolabelled with [3H]-noradrenaline. The efflux of radioactivity evoked by
      electrical field stimulation of periarterial sympathetic nerves (60 s trains of 1
      ms pulses, 2 Hz, 12 V) was taken as an index of transmitter noradrenaline
      release. Guanabenz (0.1-10 microM) decreased, in a concentration-dependent
      manner, both the resting and S-I effluxes of radioactivity. Guanethidine (0.1 and
      1 microM) also decreased S-I efflux but increased resting efflux, both effects
      being concentration dependent. The inhibitory effects of guanabenz on both
      resting and S-I effluxes were reduced by blockade of the neuronal amine carrier
      with desipramine (1 microM). The inhibitory effect of guanabenz on resting efflux
      was prevented by inhibition of monoamine oxidase with pargyline (100 microM). The
      inhibitory effect of guanabenz on S-I efflux was not due to activation of
      prejunctional alpha 2-adrenoceptors since the inhibition was not blocked by the
      selective alpha 2-adrenoceptor antagonist idazoxan (0.1 microM). However, the
      inhibitory effect of guanabenz and guanethidine on S-I efflux was reduced by the
      inhibitor of Ca(2+)-activated potassium channels apamin (0.1 microM). The
      findings suggest that guanabenz, like guanethidine, enters noradrenergic nerve
      terminals by the neuronal amine carrier. The inhibition of resting efflux
      produced by guanabenz may be due to inhibition of neuronal monoamine oxidase. The
      enhancement of resting efflux produced by guanethidine is attributable to its
      indirect sympathomimetic action. Finally, guanabenz and guanethidine may inhibit
      transmitter noradrenaline release by activating potassium channels on sympathetic
      noradrenergic nerve terminals. These findings may be relevant to the mechanism of
      adrenergic neurone blockade.

PMID- 8880889
TI  - Correction of dyslipoproteinaemia of casein-fed rabbit by FCE 27677, a potent
      novel ACAT inhibitor.
AB  - Rabbits fed a wheat starch casein diet develop hypercholesterolaemia
      characterized by the plasma elevation of low density lipoprotein (LDL) that is
      caused by oversecretion of apoB-100 containing lipoproteins by the liver and by
      the suppression of the EDTA-sensitive hepatic beta- very low density lipoprotein
      (VLDL)-LDL receptor. In this study, the effect of FCE 27677 ((-)N-[2,6-bis(1
      methylethyl)phenyl]-N'-[(4R,5R)-2-(4-dimethylaminoph eny l)-4,5-dimethyl-dioxolan
      2-yl]methylurea) a novel potent systemic acylCoA:cholesterol acetyltransferase
      (ACAT, EC 2.3.1.26) inhibitor, has been evaluated. When New Zealand White rabbits
      were fed with casein for 4 weeks, LDL cholesterol increased from 14 +/- 3 mg/dl-1
      to 77 +/- 6 mg/dl-1. By contrast the animals receiving FCE 27677 (10 mg kg-1 d-1)
      mixed with the casein diet maintained a normal LDL concentration (22 +/- 3 mg dl
      1). This hypolipidaemic effect was also observed when rabbits previously made
      hypercholesterolaemic by being fed casein for 4 weeks were then treated for a
      month with FCE 27677. [125I]LDL plasma turnover studies and [125I]LDL binding
      studies to liver membranes were carried out with the purpose of investigating the
      mechanism of action of the drug. The LDL apoB-100 production rate in chow-fed,
      casein-fed, and casein-fed rabbits receiving FCE 27677, was respectively 10.5,
      22.4, and 12.5 mg kg-1 d-1. The turnover rate of [125I]LDL in the animals
      receiving the drug was not, however, different from that in the rabbits fed the
      casein diet alone (2.381 vs 2.079 pools d-1). Both values were lower than that in
      chow-fed animals (3.271 pools d-1). FCE 27677 did not normalize the activity of
      the hepatic beta-VLDL-LDL EDTA-sensitive receptor which is suppressed by casein
      feeding. Altogether the results are consistent with the idea that FCE 27677 by
      acting through inhibition of the cholesterol esterification in the liver
      normalizes the LDL synthetic rate. ACAT inhibitors may be useful drugs for the
      treatment of human dyslipoproteinaemia secondary to derangement of the apoB-100
      synthetic rate.

PMID- 8880890
TI  - Effects of the methyl esters of pyruvate, succinate and glutamate on the
      secretory response to meglitinide analogues in rat pancreatic islets.
AB  - The insulinotropic action of the meglitinide analogues KAD-1229, A-4166 and
      repaglinide was examined in rat pancreatic islets deprived of exogenous nutrient
      or incubated in the presence of nutrient secretagogues such as D-glucose and the
      methyl esters of pyruvic acid, succinic acid and glutamic acid. The meglitinide
      analogues exerted little effect on insulin release in the absence of exogenous
      nutrient or in the presence of methyl pyruvate. They caused obvious stimulation
      of insulin output in the presence of D-glucose, dimethyl succinate or dimethyl
      glutamate. It is proposed, therefore, that suitable esters of dicarboxylic
      nutrients could be used to potentiate the secretory response to meglitinide
      analogues in non-insulin-dependent diabetes mellitus.

PMID- 8880891
TI  - G-proteins in guinea pig airway smooth muscle: identification and functional
      involvement.
AB  - In airway smooth muscle, G-proteins have not been identified directly as yet.
      This study was an attempt to detect various types of conventional Gi- and Gs
      proteins in purified membranes of guinea pig airway smooth muscle and to assess
      the involvement of the G-proteins in agonist-induced contractile response of the
      smooth muscle. Immunoblotting using AS/7 antibody which recognizes Gi-1/2
      demonstrated the presence of polypeptides of M(r) 34, 41 and 75 kDa. Polypeptides
      of M(r) 43, 46 and 48 kDa were identified with RM/1 antibody that detects Gs-type
      G-proteins. The AG/1 antibody that recognizes alpha-subunits common to all Gi-
      and Gs-proteins detected two polypeptides of M(r) 41 and 75 kDa. Heterotrimeric
      structure of the G-proteins was confirmed by the identification of a single dense
      beta-subunit band at M(r) 39 kDa with SW/1 antibody. Pertussis toxin (PT) ADP
      ribosylated three Gi alpha polypeptides of M(r) 41, 43, and 62 kDa. On the other
      hand, cholera toxin (CT) catalysed the ADP-ribosylation of two Gs alpha
      polypeptides of M(r) 46 and 62 kDa. Both PT and CT attenuated the maximum
      contractile responses of the airway smooth muscle to the muscarinic agonist,
      methacholine. Pretreatment of the tissues with the sulphydryl alkylating G
      protein inhibitor, N-ethylmaleimide, also inhibited the maximum contractions to
      methacholine. These data suggest that plasma membranes of guinea pig airway
      smooth muscle contain a variety of conventional, including Gs and Gi, and other
      types of G-proteins, and at least a portion of the proteins present may be
      involved in mediating the contractile responses of the smooth muscle to an
      agonist such as methacholine.

PMID- 8880892
TI  - Endotoxin tolerance impairs a pertussis-toxin-sensitive G-protein regulating
      tumour necrosis factor release by macrophages from tumour-bearing rats.
AB  - The aim of this work was to study whether a G-protein regulates
      lipopolysaccharide (LPS) induced TNF-alpha production in tumour-bearing rat
      peritoneal macrophages differently to in normal rats. We also investigated
      whether a state of 'early endotoxin tolerance' affects LPS induced TNF-alpha
      release via a G-protein-mediated phenomenon. LPS-stimulated (50 micrograms ml-1
      of Salmonella enteritidis LPS) TNF-alpha release was investigated in peritoneal
      macrophages harvested from both normal rats and tumour-bearing rats. Cholera
      toxin (10, 100 and 1000 ng ml-1) did not significantly modify LPS-induced TNF
      alpha release. In contrast pertussis toxin (0.1, 1.0 and 10 ng ml-1)
      significantly increased LPS-induced TNF-alpha release and inhibited LPS
      stimulated prostaglandin E2 (PGE2) production in both normal rat macrophages and
      tumour-bearing rat macrophages. Pertussis toxin effects on these LPS responses
      were correlated with a pertussis-toxin-mediated ADP-ribosylation of a 41 kDa
      protein(s). The LPS-mediated responses were significantly greater in macrophages
      from tumour-bearing rats than in macrophages from normal rats. PGE2 (10(-9), 10(
      8) and 10(-7) M) suppressed LPS-induced TNF-alpha production in a dose-dependent
      fashion. A state of 'early endotoxin tolerance' was then induced in tumour
      bearing rats by a single intravenous injection of 125 micrograms rat-1 of LPS,
      and experiments were performed on peritoneal macrophages harvested 24 h after LPS
      injection. In tolerant macrophages pertussis toxin induced an increase in LPS
      stimulated TNF-alpha release and an inhibition in LPS-stimulated PGE2 release
      significantly lower than in macrophages harvested from non-tolerant tumour
      bearing rats. Our results suggest that a pertussis-toxin-sensitive G-protein may
      serve to regulate the synthesis of TNF-alpha in rat peritoneal macrophages and
      that the activity of this pertussis-sensitive G-protein is increased in
      macrophages from tumour-bearing rats. Furthermore, our experiments would indicate
      that a 'state of endotoxin tolerance', caused by altering the function of
      presumably a Gi-protein, may exert beneficial effects on the functions of
      macrophages in tumour-bearing rats.

PMID- 8880893
TI  - Intracerebroventricular pertussis toxin enhances sensitivity to chemical
      convulsants and decreases the protective efficacy of carbamazepine in mice.
AB  - The effects of pretreatment with pertussis toxin on pentylenetetrazole-,
      bicuculline-, aminophylline- and pilocarpine-induced seizures were investigated
      in mice. In animals treated intracerebroventricularly with pertussis toxin (0.5
      microgram animal-1 120 h prior to testing), the CD50 (convulsive dose in 50%)
      values were considerably decreased in comparison with the CD50 in sham-treated
      animals. CD50 values of pentylenetetrazole, bicuculline, pilocarpine and
      aminophylline were calculated to be 39.9, 2.0, 262 and 141 mg kg-1, whereas they
      were calculated to be 57.7, 2.7, 324 and 230 mg kg-1 in sham-treated animals. The
      observations suggest that the enhanced sensitivity to a number of chemical
      convulsants irrespective of their mode of action possibly results from a
      functional suppression of inhibitory transmission at receptors coupled to
      pertussis toxin sensitive G proteins, rather than a direct action on G protein
      linked excitatory neurotransmission. Pertussis toxin significantly decreased the
      protective action of carbamazepine, increasing its ED50 (effective dose in 50%)
      from 14.8 to 20.1 mg kg-1 in a maximal electroshock convulsive test. It
      influenced the ED50 of neither diphenylhydantoin nor diazepam. The diminution of
      carbamazepine's efficacy might result from a summation effect of adenosine
      receptor antagonist properties of the drug and a suppression of transmission at
      adenosine receptors coupled to G proteins sensitive to pertussis toxin. Pertussis
      toxin pretreatment remained without any significant influence on the total plasma
      levels of carbamazepine, diphenylhydantoin and diazepam. This may lead to the
      conclusion that the interaction between pertussis toxin and carbamazepine does
      not seem to be of a pharmacokinetic nature and occurs probably at neuronal level.

PMID- 8880894
TI  - Prostaglandin I2-mediated upregulation of 125I-LDL-receptor binding by isradipine
      in normo- and hypercholesterolemic rabbits in vivo.
AB  - The in-vivo low-density lipoprotein (LDL)-uptake by the liver was monitored
      during the initial 60 minutes after injection of radiolabelled LDL. LDL-uptake by
      the liver as evidenced by the liver/blood pool ratio in normocholesterolemic male
      New Zealand white rabbits (44.2 +/- 3.1% of whole body activity) was almost
      double as compared to the ones fed a 1% cholesterol enriched diet (22.5 +/-
      3.3%). The blood disappearance of 125I-LDL was significantly faster in
      normocholesterolemic animals. A 4-week treatment with the dihydropyridine calcium
      channel blocker isradipine resulted in a significantly enhanced LDL-binding by
      the liver, both in normo- and hypercholesterolemic animals to a comparable
      extent. A concomitant acetylsalicylic acid (ASA) treatment completely abolished
      the benefit induced by isradipine while ASA alone was ineffective. Similarly,
      125I-LDL disappearance from blood was improved by isradipine, while ASA
      neutralizes this effect. Again, ASA alone did not change the kinetics. Plasma
      cholesterol and high-density lipoprotein (HDL) cholesterol remained unchanged.
      Isradipine significantly enhanced vascular prostaglandin(PG)I2-generation while
      concomitant ASA treatment or ASA application alone almost completely depressed
      PGI2-formation. It is concluded that the improved LDL-binding by the liver is due
      to an enhanced PGI2-formation evoked by isradipine.

PMID- 8880895
TI  - Inhibitory effects of interleukin-6 on release of PGI2 by cultured human
      pulmonary artery smooth muscle cells.
AB  - We evaluated the effect of interleukin-6 (IL-6) on the production of prostacyclin
      (PGI2) by cultured human pulmonary artery smooth muscle cells (HPASMC).
      Incubation of these cells for up to 48 h with IL-6 led to a dose- and time
      dependent decrease in the concentration of PGI2 in the culture medium. The
      incubation of HPASMC with 10 micrograms/ml of lipopolysaccharide (LPS), 200 U/ml
      of IL-1 beta, or 500 U/ml of TNF alpha for 24 hr significantly increased the
      concentration of PGI2 in the medium. However, the addition of IL-6 to a medium
      containing LPS, IL-1 beta, or TNF alpha significantly inhibited the stimulatory
      effect of those substances on PGI2 production. Such inhibition was closely
      related to the concentration of IL-6. IL-6 may counteract the roles of LPS and of
      other cytokines on the regulation of pulmonary vascular tension in endotoxin- and
      cytokine-mediated disorders such as sepsis and the acute respiratory distress
      syndrome (ARDS).

PMID- 8880896
TI  - PGE2 and LTB4 inhibit cytokine-stimulated nitric oxide synthase type 2 expression
      in isolated rat hepatocytes.
AB  - Prostaglandins have been shown to have a wide range of effects on nitric oxide
      synthesis when studied in different cell populations. The proximity of
      hepatocytes to eicosanoid-producing endothelial cells and Kupffer cells prompted
      us to determine the effects of PGE2 and LTB4 on hepatocyte NO production by the
      inducible nitric oxide synthase (iNOS, NOS-2) in vitro. PGE2 decreased hepatocyte
      NO synthesis in a concentration-dependent manner when the cells were stimulated
      with a combination of cytokines or IL-1 alone. LTB4 had a similar effect. PGE2
      had to be present at the time of cytokine exposure to produce maximal inhibition
      of NO synthesis. Reduced synthesis of NO2- was associated with reduced NOS-2 mRNA
      levels suggesting that the induction of NOS-2 was inhibited. These findings
      demonstrate that eicosanoids can regulate hepatocyte NO synthesis in vitro.

PMID- 8880897
TI  - Preferential formation of 13-hydroxylinoleic acid by human peripheral blood
      eosinophils.
AB  - Lipid mediators released by inflammatory and immune cells play an important role
      in inflammatory and immune processes. Most attention has been focussed on
      arachidonic-derived mediators, including prostaglandins, thromboxanes,
      leukotrienes, and lipoxins. Literature data, however, suggest that also
      metabolites of the unsaturated fatty acid linoleic acid may be important in this
      respect. We have studied the formation and release of 9-hydroxy- and 13-hydroxy
      linoleic acid (9-HODE and 13-HODE) by enriched populations of human peripheral
      blood neutrophils, eosinophils, basophils, monocytes, and lymphocytes. We
      demonstrate that the eosinophil preferentially produces 13-HODE, whereas the
      other cell types produce equal amounts of 9-HODE and 13-HODE. The biological
      significance of these findings is discussed.

PMID- 8880898
TI  - Interaction of BW A868C, a prostanoid DP-receptor antagonist, with two receptor
      subtypes in the rabbit isolated saphenous vein.
AB  - In isolated rings of rabbit saphenous vein (RbSV) pre-contracted with 40 mM KCl,
      Prostaglandin E2 (PGE2), BW245C (a DP-receptor agonist) and PGD2 caused
      concentration-dependent relaxations with mean potencies (EC50) of 0.5, 38 and 114
      nM respectively. The DP-receptor antagonist, BW A868C, antagonized BW245C
      concentration-effect (E/[A]) curves, although the corresponding Schild plot had a
      slope less than unity and displayed a clear infection. Analysis of the data
      yielded two pKB estimates of 8.5 and 4.9, the higher estimate being consistent
      with antagonism at DP-receptors. The pA2 estimate of 5.1 obtained for BW A868C
      against PGE2 was not statistically different to the lower pKB of 4.9 obtained
      against BW245C, and is probably indicative of antagonism at the EP4-receptor.
      PGD2 mediated responses were also antagonized by BW A868C, however the resultant
      E/[A] curves were 'bell shaped' in nature. The weak EP4-receptor antagonist
      AH23848B, also antagonized BW245C and PGD2 responses, yielding pA2 estimates of
      5.6 and 5.5 respectively. These results suggest that in the RbSV, BW245C and PGD2
      are nonselective agonists mediating relaxations through DP- and EP4-receptors. BW
      A868C also displayed an affinity for DP-receptors in this preparation, in
      addition to a second receptor subtype, presumably the EP4-receptor.

PMID- 8880900
TI  - Crystal structure of the 2[4Fe-4S] ferredoxin from Chromatium vinosum:
      evolutionary and mechanistic inferences for [3/4Fe-4S] ferredoxins.
AB  - The crystal structure of the 2[4Fe-4S] ferredoxin from Chromatium vinosum has
      been solved by molecular replacement using data recorded with synchrotron
      radiation. The crystals were hexagonal prisms that showed a strong tendency to
      develop into long tubes. The hexagonal prisms diffracted to 2.1 A resolution at
      best, and a structural model for C. vinosum ferredoxin has been built with a
      final R of 19.2%. The N-terminal domain coordinates the two [4Fe-4S] clusters in
      a fold that is almost identical to that of other known ferredoxins. However, the
      structure has two unique features. One is a six-residue insertion between two
      ligands of one cluster forming a two-turn external loop; this short loop changes
      the conformation of the Cys 40 ligand compared to other ferredoxins and hampers
      the building of one NH...S H-bond to one of the inorganic sulfurs. The other
      remarkable structural element is a 3.5-turn alpha-helix at the C-terminus that
      covers one side of the same cluster and is linked to the cluster-binding domain
      by a six-residue external chain segment. The charge distribution is highly
      asymmetric over the molecule. The structure of C. vinosum ferredoxin strongly
      suggests divergent evolution for bacterial [3/4Fe-4S] ferredoxins from a common
      ancestral cluster-binding core. The unexpected slow intramolecular electron
      transfer rate between the clusters in C. vinosum ferredoxin, compared to other
      similar proteins, may be attributed to the unusual electronic properties of one
      of the clusters arising from localized changes in its vicinity rather than to a
      global structural rearrangement.

PMID- 8880899
TI  - Covalent structure of the flavoprotein subunit of the flavocytochrome c: sulfide
      dehydrogenase from the purple phototrophic bacterium Chromatium vinosum.
AB  - The amino acid sequence of the flavoprotein subunit of Chromatium vinosum
      flavocytochrome c-sulfide dehydrogenase (FCSD) was determined by automated Edman
      degradation and mass spectrometry in conjunction with the three-dimensional
      structure determination (Chen Z et al., 1994, Science 266:430-432). The sequence
      of the diheme cytochrome c subunit was determined previously. The flavoprotein
      contains 401 residues and has a calculated protein mass, including FAD, of 43,568
      Da, compared with a mass of 43,652 +/- 44 Da measured by LDMS. There are six
      cysteine residues, among which Cys 42 provides the site of covalent attachment of
      the FAD. Cys 161 and Cys 337 form a disulfide bond adjacent to the FAD. The
      flavoprotein subunit of FCSD is most closely related to glutathione reductase
      (GR) in three-dimensional structure and, like that protein, contains three
      domains. However, approximately 20 insertions and deletions are necessary for
      alignment and the overall identity in sequence is not significantly greater than
      for random comparisons. The first domain binds FAD in both proteins. Domain 2 of
      GR is the site of NADP binding, but has an unknown role in FCSD. We postulate
      that it is the binding site for a cofactor involved in oxidation of reduced
      sulfur compounds. Domains 1 and 2 of FCSD, as of GR, are homologous to one
      another and represent an ancient gene doubling. The third domain provides the
      dimerization interface for GR, but is the site of binding of the cytochrome
      subunit in FCSD. The four functional entities, predicted to be near the FAD from
      earlier studies of the kinetics of sulfite adduct formation and decay, have now
      been identified from the three-dimensional structure and the sequence as Cys
      161/Cys 337 disulfide, Trp 391, Glu 167, and the positive end of a helix dipole.

PMID- 8880901
TI  - Structural characterization of the tumor suppressor p16, an ankyrin-like repeat
      protein.
AB  - The p16 protein has been identified as a tumor suppressor that functions by
      inhibiting the cyclin-dependent kinases CDK4 and CDK6. Deletions or point
      mutations in the p16 gene have been found in a number cancers, emphasizing its
      importance in regulating cell cycle progression. Inhibition by p16 occurs through
      protein-protein interactions with its targets. This is not surprising, since p16
      is thought to contain ankyrin-like repeats, motifs implicated in protein-protein
      interactions. Our goal was to identify structural characteristics of p16 not only
      as an important step towards understanding CDK4 inhibition but also to explore
      the role of ankyrin repeats in the p16 structure, as no detailed structure of any
      protein containing these motifs has been reported. We have expressed, refolded,
      and purified p16 from E. coli and have shown it to be functionally active by
      specific binding to CDK4. Analytical ultracentrifugation has shown that p16
      weakly self-associates to form dimers with a Kd = 270 microM. The CD spectrum
      indicates that the protein is composed of 33% alpha-helix, 22% beta-sheet, 19%
      beta-turn, and 27% other (which includes aromatic and random coil contributions).
      Further CD experiments suggest that p16 exhibits low structural stability with a
      delta G of -2.3 kcal/mol. This weak stability is a consequence of a highly
      dynamic structure as measured by ANS-binding, NMR hydrogen-deuterium exchange,
      and fluorescence. It is possible that a well-defined tertiary structure is
      imparted upon the binding of p16 to CDK4.

PMID- 8880902
TI  - Peptide rescue of an N-terminal truncation of the Stoffel fragment of taq DNA
      polymerase.
AB  - Deletion of the first 289 amino acids of the DNA polymerase from Thermus
      aquaticus (Taq polymerase) removes the 5' to 3' exonuclease domain to yield the
      thermostable Stoffel polymerase fragment (Lawyer et al., 1989). Preliminary N
      terminal truncation studies of the Stoffel fragment suggested that removal of an
      additional 12 amino acids (the Stof delta 12 mutant) had no significant effect on
      activity or stability, but that the further truncation of the protein (the Stof
      delta 47, in which 47 amino acids were deleted), resulted in a significant loss
      of both activity and thermostability. A 33-amino acid synthetic peptide, based on
      this critical region (i.e., residues 303-335 inclusive), was able to restore 85%
      of the Stof delta 12 activity when added back to the truncated Stof delta 47
      protein as well as return the temperature optimum to that of the Stof delta 12
      and Stoffel proteins. Examination of the crystal structure of Taq polymerase (Kim
      et al., 1995) shows that residues 302-336 of the enzyme form a three-stranded
      beta-sheet structure that interacts with the remainder of the protein. CD
      analysis of the 33-amino acid peptide indicates that the free peptide also adopts
      an ordered structure in solution with more than 50% beta-sheet content. These
      data suggest that this 33-amino acid peptide constitutes a stable beta-sheet
      structure capable of rescuing the truncated polymerase in a fashion analogous to
      the well-documented complementation of Ribonuclease S protein by the 15-residue,
      alpha-helical, S peptide.

PMID- 8880903
TI  - Electrostatic effects in electron transfer reactions of [2Fe-2S] ferredoxins with
      inorganic reagents.
AB  - The kinetics of electron transfer from the reduced [2Fe-2S] ferredoxins from the
      cyanobacterium Anabaena 7120 and the protozoan Trichomonas vaginalis to select
      cobalt coordination compounds have been studied in order to gain insight into the
      mechanism of electron transfer and intrinsic reactivity of [2Fe-2S] active sites.
      With tripositive cobalt complexes, reactions of both proteins displayed
      saturation kinetics; values of association constants of 12,900 and 1,400 M-1 and
      limiting rate constants of 7.6 and 3.5 s-1 were found for oxidation of T.
      vaginalis and Anabaena ferredoxins, respectively, by Co(NH3)6(3+) at room
      temperature and I = 0.1 M. An activation enthalpy of 12.1 kcal/mol and activation
      entropy of -14.3 cal/mol K for oxidation of T. vaginalis ferredoxin by
      Co(NH3)6(3+) contrasted with corresponding values of 13.4 kcal/mol and -10.5
      cal/mol K for the Spirulina platensis protein, which is homologous to Anabaena
      ferredoxin. The dependence of the reaction rates on ionic strength were measured
      to probe the importance of electrostatics on the reactivity of the proteins.
      Analysis of the ionic strength dependence of the oxidation of the proteins by
      Co(NH3)6(3+) by the "parallel plate" model of Watkins et al. (1994, Protein Sci
      3:2104-2114) afforded values for active site charges of -0.7 and -1.1 and
      limiting rate constants at infinite ionic strength of 25,800 and 76 M-1 S-1 for
      T. vaginalis and Anabaena ferredoxins, respectively. These results suggest that
      the [2Fe-2S] center of the protozoal ferredoxin is more accessible and adjacent
      to a less highly charged, more compact patch of negative charges than the
      photosynthetic protein.

PMID- 8880904
TI  - Improved genetic algorithm for the protein folding problem by use of a Cartesian
      combination operator.
AB  - We have devised a Cartesian combination operator and coding scheme for improving
      the performance of genetic algorithms applied to the protein folding problem. The
      genetic coding consists of the C alpha Cartesian coordinates of the protein
      chain. The recombination of the genes of the parents is accomplished by: (1) a
      rigid superposition of one parent chain on the other, to make the relation of
      Cartesian coordinates meaningful, then, (2) the chains of the children are formed
      through a linear combination of the coordinates of their parents. The children
      produced with this Cartesian combination operator scheme have similar topology
      and retain the long-range contacts of their parents. The new scheme is
      significantly more efficient than the standard genetic algorithm methods for
      locating low-energy conformations of proteins. The considerable superiority of
      genetic algorithms over Monte Carlo optimization methods is also demonstrated. We
      have also devised a new dynamic programming lattice fitting procedure for use
      with the Cartesian combination operator method. The procedure finds excellent
      fits of real-space chains to the lattice while satisfying bond-length, bond
      angle, and overlap constraints.

PMID- 8880905
TI  - An optimized g-tensor for Rhodobacter capsulatus cytochrome c2 in solution: a
      structural comparison of the reduced and oxidized states.
AB  - The optimized g-tensor parameters for the oxidized form of Rhodobacter capsulatus
      cytochrome c2 in solution were obtained using a set (50) of backbone amide
      protons. Dipolar shifts for more than 500 individual protons of R. capsulatus
      cytochrome c2 have been calculated by using the optimized g-tensor and the X-ray
      crystallographic coordinates of the reduced form of R. capsulatus cytochrome c2.
      The calculated results for dipolar shifts are compared with the observed
      paramagnetic shifts. The calculated and the observed data are in good agreement
      throughout the entire protein, but there are significant differences between
      calculated and experimental results localized to the regions in the immediate
      vicinity of the heme ligand and the region of the front crevice of the protein
      (residues 44-50, 53-57, and 61-68). The results not only indicate that the
      overall solution structures are very similar in both the reduced and oxidized
      states, but that these structures in solution are similar to the crystal
      structure. However, there are small structural changes near the heme and the
      rearrangement of certain residues that result in changes in their hydrogen
      bonding concomitant with the change in the oxidation states; this was also
      evident in the data for the NH exchange rate measurements for R. capsulatus
      cytochrome c2.

PMID- 8880906
TI  - Denaturants can accelerate folding rates in a class of globular proteins.
AB  - We present a lattice Monte Carlo study to examine the effect of denaturants on
      the folding rates of simplified models of proteins. The two-dimensional model is
      made from a three-letter code mimicking the presence of hydrophobic, hydrophilic,
      and cysteine residues. We show that the rate of folding is maximum when the
      effective hydrophobic interaction epsilon H is approximately equal to the free
      energy gain epsilon S upon forming disulfide bonds. In the range 1 < or = epsilon
      H/ epsilon S < or = 3, multiple paths that connect several intermediates to the
      native state lead to fast folding. It is shown that at a fixed temperature and
      epsilon S the folding rate increases as epsilon H decreases. An approximate model
      is used to show that epsilon H should decrease as a function of the concentration
      of denaturants such as urea or guanidine hydrochloride. Our simulation results,
      in conjunction with this model, are used to show that increasing the
      concentration of denaturants can lead to an increase in folding rates. This
      occurs because denaturants can destabilize the intermediates without
      significantly altering the energy of the native conformation. Our findings are
      compared with experiments on the effects of denaturants on the refolding of
      bovine pancreatic trypsin inhibitor and ribonuclease T1. We also argue that the
      phenomenon of denaturant-enhanced folding of proteins should be general.

PMID- 8880907
TI  - Phage display of intact domains at high copy number: a system based on SOC, the
      small outer capsid protein of bacteriophage T4.
AB  - Peptides fused to the coat proteins of filamentous phages have found widespread
      applications in antigen display, the construction of antibody libraries, and
      biopanning. However, such systems are limited in terms of the size and number of
      the peptides that may be incorporated without compromising the fusion proteins'
      capacity to self-assemble. We describe here a system in which the molecules to be
      displayed are bound to pre-assembled polymers. The polymers are T4 capsids and
      polyheads (tubular capsid variants) and the display molecules are derivatives of
      the dispensable capsid protein SOC. In one implementation, SOC and its fusion
      derivatives are expressed at high levels in Escherichia coli, purified in high
      yield, and then bound in vitro to separately isolated polyheads. In the other, a
      positive selection vector forces integration of the modified soc gene into a soc
      deleted T4 genome, leading to in vivo binding of the display protein to progeny
      virions. The system is demonstrated as applied to C-terminal fusions to SOC of
      (1) a tetrapeptide; (2) the 43-residue V3 loop domain of gp120, the human
      immunodeficiency virus type-1 (HIV-1) envelope glycoprotein; and (3) poliovirus
      VP1 capsid protein (312 residues). SOC-V3 displaying phage were highly antigenic
      in mice and produced antibodies reactive with native gp120. That the fusion
      protein binds correctly to the surface lattice was attested in averaged electron
      micrographs of polyheads. The SOC display system is capable of presenting up to
      approximately 10(3) copies per capsid and > 10(4) copies per polyhead of V3-sized
      domains. Phage displaying SOC-VP1 were isolated from a 1:10(6) mixture by two
      cycles of a simple biopanning procedure, indicating that proteins of at least 35
      kDa may be accommodated.

PMID- 8880908
TI  - Circularly permuted dihydrofolate reductase possesses all the properties of the
      molten globule state, but can resume functional tertiary structure by interaction
      with its ligands.
AB  - It is obvious that functional activity of a protein molecule is closely related
      to its structure. On the other hand, the understanding of structure-function
      relationship still remains one of the intriguing problems of molecular biology.
      There is widespread belief that mutagenesis presents a real way to solve this
      problem. Following this assumption, we have investigated the effect of circular
      permutation in dihydrofolate reductase from E. coli on protein structure and
      functioning. It has been shown that in the absence of ligands two circularly
      permuted variants of dihydrofolate reductase possess all the properties of the
      molten globule state. However, after addition of ligands they gain the native
      like structural properties and specific activity. This means that the in vitro
      folding of permuted dihydrofolate reductase is terminated at the stage of the
      molten globule formation. Interaction of permuted protein with ligands leads to
      the structural adjustment and formation of active protein molecules.

PMID- 8880909
TI  - Two partially unfolded states of Torpedo californica acetylcholinesterase.
AB  - Chemical modification with sulfhydryl reagents of the single, nonconserved
      cysteine residue Cys231 in each subunit of a disulfide-linked dimer of Torpedo
      californica acetylcholinesterase produces a partially unfolded inactive state.
      Another partially unfolded state can be obtained by exposure of the enzyme to 1-2
      M guanidine hydrochloride. Both these states display several important features
      of a molten globule, but differ in their spectroscopic (CD, intrinsic
      fluorescence) and hydrodynamic (Stokes radii) characteristics. With reversal of
      chemical modification of the former state or removal of denaturant from the
      latter, both states retain their physiochemical characteristics. Thus,
      acetylcholinesterase can exist in two molten globule states, both of which are
      long-lived under physiologic conditions without aggregating, and without either
      intraconverting or reverting to the native state. Both states undergo spontaneous
      intramolecular thioldisulfide exchange, implying that they are flexible. As
      revealed by differential scanning calorimetry, the state produced by chemical
      modification lacks any heat capacity peak, presumably due to aggregation during
      scanning, whereas the state produced by guanidine hydrochloride unfolds as a
      single cooperative unit, thermal transition being completely reversible. Sucrose
      gradient centrifugation reveals that reduction of the interchain disulfide of the
      native acetylcholinesterase dimer converts it to monomers, whereas, after such
      reduction, the two subunits remain completely associated in the partially
      unfolded state generated by guanidine hydrochloride, and partially associated in
      that produced by chemical modification. It is suggested that a novel hydrophobic
      core, generated across the subunit interfaces, is responsible for this
      noncovalent association. Transition from the unfolded state generated by chemical
      modification to that produced by guanidine hydrochloride is observed only in the
      presence of the denaturant, yielding, on extrapolation to zero guanidine
      hydrochloride, a high free energy barrier (ca. 23.8 kcal/mol) separating these
      two flexible, partially unfolded states.

PMID- 8880910
TI  - Identification of protein kinase A phosphorylation sites on NBD1 and R domains of
      CFTR using electrospray mass spectrometry with selective phosphate ion
      monitoring.
AB  - HPLC-electrospray mass spectrometry was used to identify the phosphorylated sites
      on a bacterially expressed cystic fibrosis transmembrane conductance regulator
      (CFTR) fragment containing the first nucleotide binding domain (NBD1) and the
      regulatory domain (R). Tryptic digests of NBD1-R (CFTR residues 404-830) were
      analyzed after protein kinase A (PKA) treatment for all possible peptides and
      phosphopeptides (a total of 118 species) containing Ser residues within "high
      probability" PKA consensus sequences: R-R/K-X-S/T, R-X-X-S/T, and R-X-S/T. Three
      criteria were used to assign phosphorylated sites: (1) an 80-Da increase in the
      predicted average molecular weight of the tryptic peptides; (2) co-elution with
      the PO3- ion induced by stepped energy collision; and (3) the relative elution
      positions of the phosphorylated and unmodified peptides. Ser residues within the
      eight dibasic sites in the NBD1 and R domains (positions 422, 660, 700, 712, 737,
      768, 795, and 813) were phosphorylated, a pattern similar to that observed for
      full-length CFTR. The serine at position 753, which in CFTR is phosphorylated in
      vivo, was not phosphorylated. The remaining potential PKA sites, Ser489, Ser519,
      Ser557, Ser670, and Thr788, were not phosphorylated. The "low-probability" PKA
      sites (those not containing an Arg residue) were not phosphorylated. The results
      suggest that isolated domains of CFTR developed useful models for investigating
      the biochemical and structural effects of phosphorylation within CFTR. The mass
      spectrometry approach in this study should prove useful for defining
      phosphorylation sites of CFTR in vitro and in vivo.

PMID- 8880911
TI  - High- and low-temperature unfolding of human high-density apolipoprotein A-2.
AB  - Human plasma apolipoprotein A-2 (apoA-2) is the second major protein of the high
      density lipoproteins that mediate the transport and metabolism of cholesterol.
      Using CD spectroscopy and differential scanning calorimetry, we demonstrate that
      the structure of lipid-free apoA-2 in neutral low-salt solutions is most stable
      at approximately 25 degrees C and unfolds reversibly both upon heating and
      cooling from 25 degrees C. High-temperature unfolding of apoA-2, monitored by far
      UV CD, extends from 25-85 degrees C with midpoint Th = 56 +/- 2 degrees C and
      vant Hoff's enthalpy delta H(Th) = 17 +/- 2 kcal/mol that is substantially lower
      than the expected enthalpy of melting of the alpha-helical structure. This
      suggests low-cooperativity apoA-2 unfolding. The apparent free energy of apoA-2
      stabilization inferred from the CD analysis of the thermal unfolding, delta
      G(app)(25 degrees) = 0.82 +/- 0.15 kcal/mol, agrees with the value determined
      from chemical denaturation. Enhanced low-temperature stability of apoA-2 observed
      upon increase in Na2HPO4 concentration from 0.3 mM to 50 mM or addition of 10%
      glycerol may be linked to reduced water activity. The close proximity of the heat
      and cold unfolding transitions, that is consistent with low delta G(app)(25
      degrees), indicates that lipid-free apoA-2 has a substantial hydrophobic core but
      is only marginally stable under near-physiological solvent conditions. This
      suggests that in vivo apoA-2 transfer is unlikely to proceed via the lipid-free
      state. Low delta H(Th) and low apparent delta Cp approximately 0.52 kcal/mol.K
      inferred from the far-UV CD analysis of apoA-2 unfolding, and absence of tertiary
      packing interactions involving Tyr groups suggested by near-UV CD, are consistent
      with a molten globular-like state of lipid-free apoA-2.

PMID- 8880912
TI  - Binding sites for blood coagulation factor Xa and protein S involving residues
      493-506 in factor Va.
AB  - Inactivation due to cleavage of Factor Va (FVa) at Arg 506 by activated protein C
      (APC) helps to downregulate blood coagulation. To identify potential functional
      roles of amino acids near Arg 506, synthetic overlapping pentadecapeptides
      comprising FVa heavy chain residues 481-525 were tested for their ability to
      inhibit prothrombin activation by prothrombinase complexes [Factor Xa
      (FXa):FVa:phospholipids:Ca2+]. The most potent inhibition was observed for
      peptide VP493 (residues 493-506), with 50% inhibition at 2.5 microM. VP493 also
      inhibited FXa in plasma in FXa-1-stage clotting assays by 50% at 3 microM. When
      the C-terminal carboxamide group of VP493 was replaced by a carboxyl group, most
      prothrombinase inhibitory activity was lost. VP493 preincubated with FXa
      inhibited prothrombinase with a pattern of mixed inhibition. Homologous peptides
      from Factor VIII sequences did not inhibit prothrombinase. Affinity-purified
      antibodies to VP493 inhibited prothrombinase activity and prolonged FXa-1-stage
      clotting times. VP493 also blocked the ability of protein S to inhibit
      prothrombinase independently of APC. Immobilized VP493 bound specifically with
      similar affinity to both FXa and protein S (Kd approximately 40 nM), but did not
      measurably bind prothrombin or APC. These studies suggest that FVa residues 493
      506 contribute to binding sites for both FXa and protein S, providing a rationale
      for the ability of protein S to negate the protective effect of FXa toward APC
      cleavage of FVa. Possible loss of this FVa binding site for FXa due to cleavage
      at Arg 506 by APC may help explain why this cleavage causes 40% decrease in FVa
      activity and facilitates inactivation of FVa.

PMID- 8880913
TI  - Conformational stability of adrenodoxin mutant proteins.
AB  - Adrenodoxin and the mutants at the positions T54, H56, D76, Y82, and C95, as well
      as the deletion mutants 4-114 and 4-108, were studied by high-sensitivity
      scanning microcalorimetry, limited proteolysis, and absorption spectroscopy. The
      mutants show thermal transition temperatures ranging from 46 to 56 degrees C,
      enthalpy changes from 250 to 370 kJ/mol, and heat capacity change delta Cp = 7.28
      +/- 0.67 kJ/mol/K, except H56R. The amino acid replacement H56R produces
      substantial local changes in the region around positions 56 and Y82, as indicated
      by reduced heat capacity change (delta Cp = 4.29 +/- 0.37 kJ/mol/K) and enhanced
      fluorescence. Deletion mutant 4-108 is apparently more stable than the wild type,
      as judged by higher specific denaturation enthalpy and resistance toward
      proteolytic degradation. No simple correlation between conformational stability
      and functional properties could be found.

PMID- 8880914
TI  - A dynamic bundle of four adjacent hydrophobic segments in the denatured state of
      staphylococcal nuclease.
AB  - In an earlier study of the denatured state of staphylococcal nuclease (Wang Y,
      Shortle D, 1995, Biochemistry 34:15895-15905), we reported evidence of a three
      strand antiparallel beta sheet that persists at high urea concentrations and is
      stabilized by a local "non-native" interaction with four large hydrophobic
      residues. Because the amide proton resonances for all of the involved residues
      are severely broadened, this unusual structure is not amenable to conventional
      NMR analysis and must be studied by indirect methods. In this report, we present
      data that confirm the important role of interactions involving four hydrophobic
      residues (Leu 36, Leu 37, Leu 38, and Val 39) in stabilizing the structure formed
      by the chain segments corresponding to beta 1-beta 2-beta 3-h, interactions that
      are not present in the native state. Glycine substitutions for each of these
      large hydrophobic residues destabilizes or disrupts this beta structure, as
      assessed by HN line sharpening and changes in the CD spectrum. The 13C resonances
      of the carbonyl carbon for several of the residues in this structure indicate
      conformational dynamics that respond in a complex way to addition of urea or
      changes in sequence. Studies of hydrogen exchange kinetics in a closely related
      variant of staphylococcal nuclease demonstrate the absence of the stable hydrogen
      bonding between the strands expected for a native-like three-strand beta sheet.
      Instead, the data are more consistent with the three beta strand segments plus
      the four adjacent hydrophobic residues forming a dynamic, aligned array or bundle
      held together by hydrophobic interactions.

PMID- 8880916
TI  - Dynamic NMR studies of ligand-receptor interactions: design and analysis of a
      rapidly exchanging complex of FKBP-12/FK506 with a 24 kDa calcineurin fragment.
AB  - Dynamic NMR methods, such as differential line broadening and transferred NOE
      spectroscopy, are normally reserved for the study of small molecule ligand
      interactions with large protein receptors. Using a combination of isotope
      labeling and isotope edited NMR, we have extended these techniques to
      characterize interactions of a much larger protein/drug complex, FKBP-12/ FK506
      with its receptor protein, calcineurin. In order to examine this multicomponent
      system by dynamic NMR methods, the 93 kDa, tightly bound FKBP-12/FK506/Cn complex
      was replaced with a lower affinity, rapidly exchanging system consisting of FKBP
      12/FK506 (13 kDa), recombinant calcineurin subunit B (CnB) (20 kDa), and a
      synthetic peptide (4 kDa) corresponding to the B binding domain (BBD) of
      calcineurin catalytic subunit A (CnA). Analysis of 1H-13C HSQC data acquired for
      the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that
      FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex.
      Comparison of proton line widths shows significant broadening of resonances along
      the macrocycle backbone at 13-CH, 13-OMe, 15-OMe, 18-CH2, 20-CH, 21-CH, and 25
      Me, as well as moderate broadening on the macrocycle backbone at 17-Me, 24-CH,
      and the pyranose 12-CH2 protons. The tri-substituted olefin and cyclohexyl groups
      also show moderate broadening at the 27-Me, 28-CH, and 30-CH2 positions,
      respectively. Unexpectedly, little line broadening was observed for the allyl
      resonances of FK506 in the quaternary complex, although 13C longitudinal
      relaxation measurements suggest this group also makes contacts with calcineurin.
      In addition, intermolecular transfer NOE peaks were observed for the allyl 37
      CH2, 21-CH, 30-CH2, 13-OMe, 15-OMe, 17-Me, 25-Me, and 27-Me groups, indicating
      that these are potential sites on the FK506 molecule that interact with
      calcineurin.

PMID- 8880915
TI  - Coupling between trans/cis proline isomerization and protein stability in
      staphylococcal nuclease.
AB  - The nucleases A produced by two strains of Staphylococcus aureus, which have
      different stabilities, differ only in the identity of the single amino acid at
      residue 124. The nuclease from the Foggi strain of S. aureus (by convention
      nuclease WT), which contains His124, is 1.9 kcal.mol-1 less stable (at pH 5.5 and
      20 degrees C) than the nuclease from the V8 strain (by convention nuclease
      H124L), which contains Leu124. In addition, the population of the trans conformer
      at the Lys116-Pro117 peptide bond, as observed by NMR spectroscopy, is different
      for the two variants: about 15% for nuclease WT and 9% for nuclease H124L. In
      order to improve our understanding of the origin of these differences, we
      compared the properties of WT and H124L with those of the H124A and H124I
      variants. We discovered a correlation between effects of different residues at
      this position on protein stability and on stabilization of the cis configuration
      of the Lys116-Pro117 peptide bond. In terms of free energy, approximately 17% of
      the increase in protein stability manifests itself as stabilization of the cis
      configuration at Lys116-Pro117. This result implies that the differences in
      stability arise mainly from structural differences between the cis
      configurational isomers at Pro117 of the different variants at residue 124. We
      solved the X-ray structure of the cis form of the most stable variant, H124L, and
      compared it with the published high-resolution X-ray structure of the cis form of
      the most stable variant, WT (Hynes TR, Fox RO, 1991, Proteins Struct Funct Genet
      10:92-105). The two structures are identical within experimental error, except
      for the side chain at residue 124, which is exposed in the models of both
      variants. Thus, the increased stability and changes in the trans/cis equilibrium
      of the Lys116-Pro117 peptide bond observed in H124L relative to WT are due to
      subtle structural changes that are not observed by current structure
      determination technique. Residue 124 is located in a helix. However, the
      stability changes are too large and follow the wrong order of stability to be
      explained simply by differences in helical propensity. A second site of
      conformational heterogeneity in native nuclease is found at the His46-Pro47
      peptide bond, which is approximately 80% trans in both WT and H124L. Because
      proline to glycine substitutions at either residue 47 or 117 remove the
      structural heterogeneity at that position and increase protein stability, we
      determined the X-ray structures of H124L + P117G and H124L + P47G + P117G and the
      kinetic parameters of H124L, H124L + P47G, H124L + P117G, and H124L + P47G +
      P117G. The individual P117G and P47G mutations cause decreases in nuclease
      activity, with kcat affected more than Km, and their effects are additive. The
      P117G mutation in nuclease H124L leads to the same local conformational
      rearrangement described for the P117G mutant of WT (Hynes TR, Hodel A, Fox RO,
      1994, Biochemistry 33:5021-5030). In both P117G mutants, the loop formed by
      residues 112-117 is located closer to the adjacent loop formed by residues 77-85,
      and residues 115-118 adopt a type I' beta-turn conformation with the Lys116
      Gly117 peptide bond in the trans configuration, as compared with the parent
      protein in which these residues have a typeVIa beta-turn conformation with the
      Lys116-Pro117 peptide bond in the cis configuration. Addition of the P47G
      mutation appears not to cause any additional structural changes. However, the
      electron density for part of the loop containing this peptide bond was not strong
      enough to be interpreted.

PMID- 8880917
TI  - Homology modeling of human methylmalonyl-CoA mutase: a structural basis for point
      mutations causing methylmalonic aciduria.
AB  - Point mutations in the human gene encoding coenzyme B12 (adenosylcobalamin)
      dependent methylmalonyl-CoA mutase give rise to an inherited disorder of
      propionic acid metabolism termed mut methylmalonic aciduria. Almost all such
      mutations alter amino acids in the homodimeric human enzyme that are identical to
      residues in the catalytic alpha-subunit of the heterodimeric methylmalonyl-CoA
      mutase from the bacterium Propionibacterium shermanii, to which the mature human
      enzyme shows an overall 65% sequence identity. To explore how specific mutations
      might cause the observed clinical phenotype, 12 known mutations were mapped onto
      a three-dimensional homology model of the subunit of the human enzyme, generated
      using the program MODELLER on the basis of the recently published 2.0 A X-ray
      crystal structure of the P. shermanii methylmalonyl-CoA mutase. Eight mutations
      are found in the C-terminal B12-binding domain, of which 4 (G623R, G626C, G630E,
      G703R) are in direct contact with the corrin and are clustered around the
      histidine ligand (H627) provided by the protein to coordinate the cobalt atom of
      the B12 cofactor. Introduction of a side chain, particularly one that is charged,
      at any of these positions is expected to disrupt the flavodoxin-like fold and
      severely impair its binding of B12. Mutation at either of two other highly
      conserved glycine residues in this domain (G648D, G717V) also disrupts critical
      elements in the fold as would the introduction of an additional positive charge
      in the mutation H678R. Mutation of an arginine in a solvent-exposed loop to a
      hydrophobic residue (R694W) is also pathogenic. The remaining mutations have been
      mapped to the N-terminal region of the mutase, two of which introduce a buried,
      uncompensated charge, either near the subunit interface (A377E), or near the
      narrow channel through which acyl-CoA esters gain access to the active site
      (W105R). The extreme N-terminus of methylmalonyl-CoA mutase is predicted to make
      extensive contacts with the other subunit, and a mutant in this region (R93H) may
      prevent the correct assembly of the dimer.

PMID- 8880918
TI  - Purification and crystallization of cyclin-dependent kinase inhibitor p21.
AB  - p21, a universal inhibitor of mammalian cyclin-dependent kinases (CDK), regulates
      cell cycle progression by forming various distinct protein complexes with
      cyclins, CDKs, and the proliferating cell nuclear antigen. We have overexpressed
      recombinant human p21 in E. coli and purified active p21 to near homogeneity on a
      large scale. Crystals of recombinant p21 have been grown in the space group P2(1)
      a = 157.4, b = 152.7, c = 90.6 A, and beta = 92.7 degrees. The diffraction data
      of the recombinant p21 have been collected to 2.5 and 3.5 A resolution for the
      native crystal and two heavy atom derivatives of mercury and iridium.

PMID- 8880919
TI  - Crystallization and preliminary X-ray diffraction studies of the Lb proteinase
      from foot-and-mouth disease virus.
AB  - Different crystal forms of the C23A mutant from the leader proteinase of foot-and
      mouth disease virus were obtained by the hanging drop vapor diffusion technique,
      using MgCl2 and PEG 6000 as precipitants. Well-developed crystals, with cubic
      morphology growing to approximately 1.0 mm3 in size, presented a large unit cell
      parameter of 274.5 A and diffracted to, at most, 5 A resolution. A second type of
      crystal had a tetragonal appearance and these were obtained in droplets soaked in
      a silica gel matrix. These crystals, with an approximate size of 0.3 X 0.3 X 0.7
      mm3, diffracted to approximately 4.0 A resolution, but presented a strong
      anisotropic mosaicity around the longest crystal axis. Crystals with a needlelike
      morphology and reaching sizes of about 0.2 X 0.3 X 1.2 mm3 diffracted beyond 3.5
      A resolution and were stable to X-ray radiation for approximately one day when
      using a conventional source at room temperature. These crystals are orthorhombic
      with space group I222 (or I2(1)2(1)2(1)) and unit cell dimensions a = 65.9 A, b =
      104.3 A, and c = 124.0 A, and appear well suited for high-resolution studies.
      Density packing considerations are consistent with the presence of two molecules
      in the asymmetric unit and a solvent content of approximately 54%.

PMID- 8880920
TI  - Conformational flexibility and crystallization of tandemly linked type III
      modules of human fibronectin.
AB  - Fibronectin is a large cell adhesion molecule that is composed of several
      functional domains. The cell-binding domain that binds to cell surface integrins
      consists of repeated homologous type III modules. In this study, recombinant
      fragments from the cell-binding domain of human fibronectin that participate in a
      newly characterized fibronectin-fibronectin interaction with FNIII1 were
      crystallized. In each case, the crystals had more than one fibronectin fragment
      in the asymmetric unit. Crystals of FNIII10-11 grew in the space group C2 with a
      = 117.1 A, b = 38.6 A, c = 80.6 A, beta = 97.2 degrees, and two molecules in the
      asymmetric unit. These crystals diffracted to 2.5 A resolution. Fragment FNIII8
      11 and a shorter fragment, FNIII8-10, crystallized in hexagonal space groups with
      large unit cells and two to four molecules per asymmetric unit. Even very large
      crystals of these fragments did not diffract beyond 4 A. The crystal packing for
      this collection of fibronectin fragments suggests conformational flexibility
      between linked type III modules. The functional relevance of this flexibility for
      elongated versus compact models of the cell-binding domain of fibronectin is
      discussed.

PMID- 8880921
TI  - Members of the immunoglobulin superfamily in bacteria.
AB  - We report a prediction that two prokaryotic proteins contain immunoglobulin
      superfamily domains. Immunoglobulin-like folds have been identified previously in
      prokaryotic proteins, but these share no recognizable sequence similarity with
      eukaryotic immunoglobulin superfamily (IgSF) folds, and may be the result of the
      physics and chemistry of proteins favoring certain common folds. In contrast, the
      prokaryotic proteins identified have sequences whose match to the immunoglobulin
      superfamily can be detected by hidden Markov modeling, BLASTP matches, key
      residue analysis, and secondary structure predictions. We propose that these
      prokaryotic immunoglobulin-like domains are almost certain to be related by
      divergence from a common ancestor to eukaryotic immunoglobulin superfamily
      domains.

PMID- 8880923
TI  - The chemical synthesis of proteins.

PMID- 8880922
TI  - A fragment of staphylococcal nuclease with an OB-fold structure shows hydrogen
      exchange protection factors in the range reported for "molten globules".
AB  - Hydrogen-exchange rates for an OB-fold subdomain fragment of staphylococcal
      nuclease have been measured at pH 4.7 and 4 degrees C, conditions close to the
      minimum of acid/base catalyzed exchange. The strongest protection from solvent
      exchange is observed for residues from a five-stranded beta-barrel in the NMR
      structure of the protein. Protection factors, calculated from the experimental
      hydrogen-exchange rates, range between 1 and 190. Similarly small protection
      factors have in many cases been attributed to "molten globule" conformations that
      are supposed to lack a specific tertiary structure. The present results suggest
      that marginal protection from solvent exchange does not exclude well-defined
      structure.

PMID- 8880924
TI  - No crystals no grant.

PMID- 8880925
TI  - Building self-avoiding lattice models of proteins using a self-consistent field
      optimization.
AB  - We present an algorithm to build self-avoiding lattice models of chain molecules
      with low RMS deviation from their actual 3D structures. To find the optimal
      coordinates for the lattice chain model, we minimize a function that consists of
      three terms: (1) the sum of squared deviations of link coordinates on a lattice
      from their off-lattice values, (2) the sum of "short-range" terms, penalizing
      violation of chain connectivity, and (3) the sum of "long-range" repulsive terms,
      penalizing chain self-intersections. We treat this function as a chain molecule
      "energy" and minimize it using self-consistent field (SCF) theory to represent
      the pairwise link repulsions as 3D fields acting on the links. The statistical
      mechanics of chain molecules enables computation of the chain distribution in
      this field on the lattice. The field is refined by iteration to become self
      consistent with the chain distribution, then dynamic programming is used to find
      the optimal lattice model as the "lowest-energy" chain pathway in this SCF. We
      have tested the method on one of the coarsest (and most difficult) lattices used
      for model building on proteins of all structural types and show that the method
      is adequate for building self-avoiding models of proteins with low RMS deviations
      from the actual structures.

PMID- 8880926
TI  - Structural model of the anti-snake-toxin antibody, M alpha 2,3.
AB  - We present results of structural modeling of the variable fragment of M alpha
      2,3, an antibody capable of neutralizing all short snake toxins. Three different
      methods were used to model the hypervariable loops: the conformational search
      algorithm CONGEN (Bruccoleri and Karplus, Biopolymers 26:137-168, 1987), high
      temperature molecular dynamics (Bruccoleri and Karplus, Biopolymers 29:1847-1862,
      1990), and a combined knowledge-based and energy-based algorithm (Martin et al.,
      Proc. Natl. Acad. Sci. USA 86:9268-9272, 1989). Ninety plausible conformations
      were generated and were clustered into 13 classes. The clustering results
      indicate that there was little overlap of the conformational space explored by
      the different methods. Canonical loop structures were found by all methods for
      two of the loops, in agreement with previously established empirical modeling
      criteria. Nine of the 13 classes of structure were rejected on the ground of
      their lacking common features of antibody combining-site structure. The remaining
      four models were refined using restrained molecular dynamics. It was found that
      interconversion between the four resulting structures is possible with no
      significant energy barriers, suggesting that they are in thermodynamic
      equilibrium at 300 K. Features of the combining-site structure likely to be
      particularly important for antigen binding are discussed.

PMID- 8880927
TI  - Electrostatic properties deduced from refined structures of NADH-cytochrome b5
      reductase and the other flavin-dependent reductases: pyridine nucleotide-binding
      and interaction with an electron-transfer partner.
AB  - Electrostatic properties on the protein surface were examined on the basis of the
      crystal structure of NADH-cytochrome b5 reductase refined to a crystallographic R
      factor of 0.223 at 2.1 A resolution and of the other three flavin-dependent
      reductases. A structural comparison of NADH-cytochrome b5 reductase with the
      other flavin-dependent reductases, ferredoxin-NADP+ reductase, phthalate
      dioxygenase reductase, and nitrate reductase, showed that the alpha/beta
      structure is the common motif for binding pyridine nucleotide. Although the amino
      acid residues associated with pyridine nucleotide-binding are not conserved, the
      electrostatic properties and the location of the pyridine nucleotide-binding
      pockets of NADH-requiring reductases were similar to each other. The
      electrostatic potential of the surface near the flavin-protruding side
      (dimethylbenzene end of the flavin ring) of NADH-cytochrome b5 reductase was
      positive over a wide area while that of the surface near the heme-binding site of
      cytochrome b5 was negative. This implied that the flavin-protruding side of NADH
      cytochrome b5 reductase is suitable for interacting with its electron-transfer
      partner, cytochrome b5. This positive potential area is conserved among four
      flavin-dependent reductases. A comparison of the electron-transfer partners of
      four flavin-dependent reductases showed that there are significant differences in
      the distribution of electrostatic potential between inter-molecular and inter
      domain electron-transfer reactions.

PMID- 8880928
TI  - Computational simulations of stem-cell factor/c-kit receptor interaction.
AB  - Stem-cell factor (SCF) is a noncovalent homodimeric cytokine that exhibits
      profound biological function in the early stages of hematopoiesis by binding to a
      cell surface tyrosine kinase receptor that is encoded by the c-Kit proto
      oncogene. The results obtained from a combined implementation of homology-based
      molecular modeling and computational simulations in the study of species-specific
      SCF/ c-Kit interactions are reported. The structural models of the human and rat
      SCF ligands are based on the close structural similarity to the cytokine M-CSF,
      whose C alpha structure has recently become available. The constant domains of
      the human Fc fragment are used as a template for the ligand binding domains of
      the c-Kit receptor. The factors responsible for the stabilization of the SCF
      quaternary structure and the molecular determinants for ligand recognition and
      ligand specificity have been identified by assessing the conformational,
      topographical, and dynamic features of the isolated ligands and of the ligand
      receptor complexes.

PMID- 8880929
TI  - Refined structures of bobwhite quail lysozyme uncomplexed and complexed with the
      HyHEL-5 Fab fragment.
AB  - The HyHEL-5 antibody has more than a thousandfold lower affinity for bobwhite
      quail lysozyme (BWQL) than for hen egg-white lysozyme (HEL). Four sequence
      differences exist between BWQL and HEL, of which only one is involved in the
      interface with the Fab. The structure of bobwhite quail lysozyme has been
      determined in the uncomplexed state in two different crystal forms and in the
      complexed state with HyHEL-5, an antihen egg-white lysozyme Fab. Similar backbone
      conformations are observed in the three molecules of the two crystal forms of
      uncomplexed BWQL, although they show considerable variability in side-chain
      conformation. A relatively mobile segment in uncomplexed BWQL is observed to be
      part of the HyHEL-5 epitope. No major backbone conformational differences are
      observed in the lysozyme upon complex formation, but side-chain conformational
      differences are seen in surface residues that are involved in the interface with
      the antibody. The hydrogen bonding in the interface between BWQL and HyHEL-5 is
      similar to that in previously determined lysozyme-HyHEL-5 complexes.

PMID- 8880930
TI  - Structural stability of disulfide mutants of basic pancreatic trypsin inhibitor:
      a molecular dynamics study.
AB  - The structure and folding of basic pancreatic trypsin inhibitor (BPTI) has been
      studied extensively by experimental means. We report a computer simulation study
      of the structural stability of various disulfide mutants of BPTI, involving eight
      250-psec molecular dynamics simulations of the proteins in water, with and
      without a phosphate counterion. The presence of the latter alters the relative
      stability of the single disulfide species [5-55] and [30-51]. This conclusion can
      explain results of mutational studies and the conservation of residues in
      homologues of BPTI, and suggests a possible role of ions in stabilizing one
      intermediate over another in unfolding or folding processes.

PMID- 8880931
TI  - A comparative study of dynamic structures between phage 434 Cro and repressor
      proteins by normal mode analysis.
AB  - Two DNA binding proteins, Cro and the amino-terminal domain of the repressor of
      bacteriophage 434 (434 Cro and 434 repressor) that regulate gene expression and
      contain a helix-turn-helix (HTH) motif responsible for their site-specific DNA
      recognition adopt very similar three-dimensional structures when compared to each
      other. To reveal structural differences between these two similar proteins, their
      dynamic structures, as examined by normal mode analysis, are compared in this
      paper. Two kinds of structural data, one for the monomer and the other for a
      complex with DNA, for each protein, are used in the analyses. From a comparison
      between the monomers it is found that the interactions of Ala-24 in 434 Cro or
      Val-24 in 434 repressor, both located in the HTH motif, with residues 44, 47, 48,
      and 51 located in the domain facing the motif, and the interactions between
      residues 17, 18, 28, and 32, located in the HTH motif, cause significant
      differences in the correlative motions of these residues. From the comparison
      between the monomer and the complex with DNA for each protein, it was found that
      the first helix in the HTH motif is distorted in the complex form. While the
      residues in the HTH motif in 434 Cro have relatively larger positive correlation
      coefficients of motions with other residues within the HTH motif, such
      correlations are not large in the HTH motif of 434 repressor. It is suggestive to
      their specificity because the 434 repressor is less specific than 434 Cro.
      Although a structural comparison of proteins has been performed mainly from a
      static or geometrical point of view, this study demonstrates that the comparison
      from a dynamic point of view, using the normal mode analysis, is useful and
      convenient to explore a difference that is difficult to find only from a
      geometrical point of view, especially for proteins very similar in structure.

PMID- 8880932
TI  - A database of mutants and effects of site-directed mutagenesis experiments on G
      protein-coupled receptors.
AB  - A database system and computer programs for storage and retrieval of information
      about guanine nucleotide-binding protein (G protein) -coupled receptor mutants
      and associated biological effects have been developed. Mutation data on the
      receptors were collected from the literature and a database of mutants and
      effects of mutations was developed. The G protein-coupled receptor, family A,
      point mutation database (GRAP) provides detailed information on ligand-binding
      and signal transduction properties of more than 2130 receptor mutants. The amino
      acid sequences of receptors for which mutation experiments have been reported
      were aligned, and from this alignment mutation data may be retrieved.
      Alternatively, a search form allowing detailed specification of which mutants to
      retrieve may be used, for example, to search for specific amino acid
      substitutions, substitutions in specific protein domains or reported biological
      effects. Furthermore, ligand and bibliographic oriented queries may be performed.
      GRAP is available on the Internet (URL: http://www-grap.fagmed.uit.no/GRAP/+
      +homepage.html) using the World-Wide Web system.

PMID- 8880933
TI  - Requirements for perpendicular helix pairing.
AB  - Cassette mutagenesis was used to produce a library of mutations at the interface
      of the N- and C-terminal helices of Saccharomyces cerevisiae iso-1-cytochrome c.
      The library is random and comprises > 98% mutations. Over 11,000 candidates were
      assayed for function by selecting for the ability of yeast, with the mutated gene
      as their sole cytochrome c source, to grow on nonfermentable carbon sources. We
      estimate that approximately 0.5% of the 160,000 total amino acid combinations at
      these four residues result in a functional cytochrome c. Significant correlations
      are found between the phenotype of yeast harboring the alleles and both the
      Dayhoff mutation matrix and transfer free energies (cyclohexane-to-water and n
      octanol-to-water). Similar correlations are observed with respect to growth rate.
      Finally, sequences that are consistent with function follow a binary amino acid
      pattern.

PMID- 8880934
TI  - Purification and crystallization of a complex between human interferon gamma
      receptor (extracellular domain) and human interferon gamma.
AB  - X-ray diffraction quality crystals have been obtained from a complex between
      interferon gamma and the extracellular domain of its high-affinity cell surface
      receptor. The crystals were obtained from interferon gamma/interferon gamma
      receptor complexes purified by size exclusion chromatography. Diffraction quality
      crystals required analyzing these complex samples by isoelectric focusing gels to
      select purified complex fractions devoid of unbound interferon gamma. These
      studies used interferon gamma receptor engineered with an eight amino acid N
      terminal deletion to eliminate heterogeneity generated due to proteolytic
      cleavage. In addition, the receptor was expressed in an E. coli secretion cell
      line which eliminated the need to refold the protein. Hexagonal crystals were
      grown from 1.6 M ammonium phosphate solutions and belong to a spacegroup of
      P6(5)22 with unit cell dimensions a = 145.9 A and c = 180.3 A. These crystals
      diffract to at least 2.9 A resolution when exposed to synchrotron radiation. SDS
      PAGE analysis of the crystals demonstrated that both interferon gamma and the
      receptor were present. Analysis of the x-ray diffraction data revealed that the
      crystals contain complexes with a stoichiometry of 2:1 receptor: ligand within
      the crystallographic asymmetric unit and consist of approximately 55% solvent.

PMID- 8880935
TI  - Crystallization and preliminary crystallographic analysis of
      tetrahydrodipicolinate-N-succinyltransferase.
AB  - Crystals of tetrahydrodipicolinate-N-succinyltransferase have been obtained from
      solutions containing 2-propanol and polyethylene glycol 4,000. These crystals
      belong to the monoclinic space group P2(1), diffract X-rays to a resolution of
      2.2 A, and contain one trimer per asymmetric unit.

PMID- 8880936
TI  - Crystallization and preliminary X-ray diffraction studies of formylmethanofuran:
      tetrahydromethanopterin formyltransferase from Methanopyrus kandleri.
AB  - Formylmethanofuran:tetrahydromethanopterin formyltransferase from the
      hyperthermophilic methanogenic Archaeon Methanopyrus kandleri (growth temperature
      optimum 98 degrees C) was crystallized by vapor diffusion methods. Crystal form M
      obtained with 2-methyl-2,4-pentanediol as precipitant displayed the space group
      P2(1) with unit cell parameters of a = 87.0 A, b = 75.4 A, c = 104.7 A, and beta
      = 113.9 degrees and diffracted better than 2 A resolution. Crystal form P grown
      from polyethylene glycol 8000 belonged to the space group I4(1)22 and had unit
      cell parameters of 157.5 A and 242.1 A. Diffraction data to 1.73 A were recorded.
      Crystal form S which was crystallized from (NH4)2SO4 in the space group I4(1)22
      with unit cell parameters of 151.3 A and 249.5 A diffracted at least to 2.2 A
      resolution. All crystal forms probably have four molecules per asymmetric unit
      and are suitable for X-ray structure analysis.

PMID- 8880937
TI  - The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and
      antinociceptive actions that are reversed by D-serine.
AB  - This report describes the activity of the antiepileptic agent gabapentin
      (Neurontin) in animal models predictive of anxiolysis and analgesia. Gabapentin
      displayed anxiolytic-like action in the rat conflict test, the mouse light/dark
      box and the rat elevated X-maze with respective minimum effective doses (MEDs) of
      3, 10 and 30 mg/kg. Furthermore, gabapentin also induced behavioural changes
      suggestive of anxiolysis in the marmoset human threat test with a MED of 30
      mg/kg. In the rat formalin test of tonic nociception, gabapentin dose-dependently
      (30-300 mg/kg) and selectively blocked the late phase with a MED of 100 mg/kg.
      However, it failed to block carrageenan-induced paw oedema. The
      intracerebroventricular (ICV) administration of the glycine/NMDA receptor agonist
      D-Serine, dose-dependently (10-100 micrograms/animal) reversed the
      antinociceptive action of gabapentin (200 mg/kg, SC). D-Serine (30
      micrograms/animal, ICV) also reversed the anxiolytic-like effects (in the
      light/dark box and the rat elevated X-maze) of gabapentin (30 mg/kg). In
      contrast, L-Serine (100 micrograms, ICV) failed to block the antinociceptive
      action of gabapentin. The antinociceptive action of (+)-HA-966 (25 mg/kg, SC), a
      partial agonist at the glycine/NMDA receptor, was reversed by D-Serine (100
      micrograms/animal, ICV). However, D-Serine (100 micrograms/animal, ICV) failed to
      affect the antinociceptive action of a competitive NMDA receptor antagonist CGS
      19755 (3 mg/kg, SC). Gabapentin has negligible affinity for the strychnine
      insensitive [3H]glycine binding site. This indicates that the interaction between
      gabapentin and D-Serine may not involve the NMDA receptor complex. Gabapentin may
      represent a novel type of anxiolytic and analgesic agent.

PMID- 8880938
TI  - Pharmacological screen for activities of 12-hydroxyibogamine: a primary
      metabolite of the indole alkaloid ibogaine.
AB  - The purported efficacy of ibogaine for the treatment of drug dependence may be
      due in part to an active metabolite. Ibogaine undergoes first pass metabolism and
      is O-demethylated to 12-hydroxyibogamine (12-OH ibogamine). Radioligand binding
      assays were conducted to identify the potency and selectivity profiles for
      ibogaine and 12-OH ibogamine. A comparison of 12-OH ibogamine to the primary
      molecular targets identified previously for ibogaine demonstrates that the
      metabolite has a binding profile that is similar, but not identical to the parent
      drug. Both ibogaine and 12-OH ibogamine demonstrated the highest potency values
      at the cocaine recognition site on the 5-HT transporter. The same rank order (12
      OH ibogamine > ibogaine), but lower potencies were observed for the
      [3H]paroxetine binding sites on the 5-HT transporter. Ibogaine and 12-OH
      ibogamine were equipotent at vesicular monoamine and dopamine transporters. The
      metabolite demonstrated higher affinity at the kappa-1 receptor and lower
      affinity at the NMDA receptor complex compared to the parent drug. Quantitation
      of the regional brain levels of ibogaine and 12-OH ibogamine demonstrated
      micromolar concentrations of both the parent drug and metabolite in rat brain.
      Drug dependence results from distinct, but inter-related neurochemical
      adaptations, which underlie tolerance, sensitization and withdrawal. Ibogaine's
      ability to alter drug-seeking behavior may be due to combined actions of the
      parent drug and metabolite at key pharmacological targets that modulate the
      activity of drug reward circuits.

PMID- 8880939
TI  - The antidepressant drug phenelzine produces antianxiety effects in the plus-maze
      and increases in rat brain GABA.
AB  - Research on the effects of antidepressant/ antipanic drugs in animal models of
      anxiety has yielded equivocal results, even after chronic drug regimens. In
      contrast, we found that the antidepressant/antipanic drug phenelzine, given
      acutely, produced a clear anxiolytic effect in the elevated plus-maze, a widely
      used animal model of "anxiety" that is primarily sensitive to benzodiazepine-type
      anxiolytics (e.g., diazepam). Furthermore, the effective dose of phenelzine (15
      mg/kg) administered to rats was associated with more than a 2- fold increase in
      whole brain levels of gamma-aminobutyric acid (GABA), whereas an ineffective dose
      of phenelzine (5.1 mg/kg) did not significantly change GABA levels. The N
      acetylated metabolite of phenelzine, N2-acetylphenelzine, produced neither an
      anxiolytic effect in the elevated plus-maze nor a significant change in whole
      brain levels of GABA. However, both phenelzine and N2-acetylphenelzine potently
      inhibited monoamine oxidase, a mechanism commonly thought to be involved in the
      therapeutic effects of monoamine oxidase inhibitors such as phenelzine in the
      treatment of depression in humans. These results suggest that the mechanism
      whereby phenelzine produces anxiolytic effects in the plus-maze model is unique
      to a facilitatory action on brain levels of GABA, in contrast to classical
      benzodiazepines, which produce anxiolytic effects by enhancing the affinity of
      the GABAA-receptor for GABA.

PMID- 8880940
TI  - Chronic nicotine working and reference memory effects in the 16-arm radial maze:
      interactions with D1 agonist and antagonist drugs.
AB  - Chronic nicotine infusion has been found in a series of studies in our laboratory
      to significantly improve choice accuracy of rats in the eight-arm radial maze.
      The current study was designed to compare the effects of chronic nicotine
      infusion on working and reference memory in a 16-arm radial maze. Nicotine was
      administered to female Sprague-Dawley rats at approximately 5 mg/kg per day SC
      via osmotic minipumps. Controls received saline infusions. Chronic nicotine
      infusion significantly lowered the number of working memory errors compared to
      controls, whereas the number of reference memory errors was not significantly
      affected. The modest nicotine-induced reduction in working memory errors was seen
      as a main effect over the 4 weeks of infusion, but the clearest effect was seen
      in weeks 3-4 of nicotine administration. For the 2 weeks after withdrawal, the
      nicotine effect was no longer evident. Acute D1 challenges were given with the D1
      agonist dihydrexidine (0, 0.25, 0.5 and 1 mg/kg) and the D1 antagonist SCH 23390
      (0, 0.005, 0.015 and 0.05 micrograms/kg) during weeks 3-4 of chronic nicotine
      administration and weeks 1-2 after withdrawal from nicotine. Dihydrexidine caused
      a modest dose-related increase in reference memory errors but not working memory
      errors in the nicotine-treated, but not the control rats. The D1 antagonist SCH
      23390 caused a modest though significant decrease in reference memory errors but
      not working memory errors in the control, but not the nicotine-treated rats. The
      behavioral specificity of chronic nicotine infusion was demonstrated with
      selective improvement in working memory function. Pharmacological interactions
      were seen with chronic nicotine treatment increasing responsivity to D1 agonist
      and decreasing responsivity to a D1 antagonist with regard to reference memory.
      The mechanisms of this interaction are still undiscovered.

PMID- 8880941
TI  - Cognitive performance effects of subcutaneous nicotine in smokers and never
      smokers.
AB  - In a double-blind placebo-controlled crossover study the effects of two doses of
      subcutaneous nicotine and saline were compared on a range of performance measures
      in 18 abstaining smokers and 18 never-smokers. Each subject received two
      injections (40 min apart) of saline, 0.3 mg nicotine, or 0.6 mg nicotine in a
      balanced order over three sessions. Performance was assessed before and after the
      injections on nine tests [news recall, Sternberg memory task, finger tapping,
      logical reasoning, rapid visual information processing (RVIP), long-term word
      recognition, digit recall, Stroop test, and critical flicker fusion threshold].
      In the abstinent smokers, nicotine produced significantly faster correct
      responses on the logical reasoning test, more target hits, faster reaction times
      and improved sensitivity on the RVIP task, and more correct responses on word
      recognition. In never-smokers, nicotine produced faster reaction times on the
      RVIP and digit-recall tasks, although in the latter case this was at the expense
      of fewer correct responses. There were no significant differences between the two
      groups' responses to nicotine but smokers performed worse than never-smokers
      prior to injections, even controlling for background characteristics. These
      results are consistent with other recent research suggesting a primary effect of
      nicotine in enhancing cognitive performance.

PMID- 8880942
TI  - Amphetamine self-administration by humans: modulation by contingencies associated
      with task performance.
AB  - The effect of task performance feedback and associated monetary earnings on drug
      self-administration were evaluated using eight subjects in a residential
      laboratory setting. The hypothesis was that if subjects believed that d
      amphetamine impaired performance and reduced monetary earnings, d-amphetamine
      self-administration would decrease. Subjects performed computer tasks every day:
      on certain days that they received capsules, subjects were given bogus feedback
      regarding their performance ("better" or "worse" than average). On sample days,
      subjects were required to take d-amphetamine (10 mg BID) or placebo (0 mg BID)
      capsules. On choice days, subjects could choose between either d-amphetamine or
      placebo. Subjects received feedback on their task performance on 2 sample days
      and 2 of 4 choice days. Subjects received no feedback on the remaining two choice
      days. When subjects received no feedback, they chose d-amphetamine over placebo
      78% of the time, and when they were given better feedback messages, they chose d
      amphetamine 87.5% of the time. In contrast, d-amphetamine self-administration
      decreased significantly to 25% when subjects were told that it impaired their
      performance on work tasks and resulted in reduced earnings. In reality, d
      amphetamine had little effect on work task performance. However, compared to
      placebo, d-amphetamine significantly increased subjective ratings of "Stimulated"
      and "Good Drug Effect" and significantly decreased ratings of "Tired" and
      "Sleepy." These results demonstrate that d-amphetamine served as a reinforcer
      under conditions in which drug self-administration did not influence monetary
      earnings, but that d-amphetamine self-administration could be modified by
      feedback/monetary earnings. Thus, contingencies associated with performance have
      important implications for drug use in the workplace.

PMID- 8880944
TI  - Assessing the sensory role of nicotine in cigarette smoking.
AB  - Thirty-two subjects were tested in five double-blind sessions (16 subjects in the
      morning following overnight smoking abstention, and 16 in the afternoon following
      ad-lib smoking). In each session, subjects smoked one of five experimental (EX)
      cigarettes having the following FTC nicotine/"tar' yields in mg: 0.08/8.5,
      0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. In a sixth session, subjects smoked
      a 0.71/8.6 commercial "light' (CL) cigarette that was their usual brand. Before
      and after smoking, subjects subjectively rated their desire to smoke a cigarette
      of their usual brand and had blood samples drawn. Following smoking, subjects
      rated the cigarette on a variety of sensory dimensions; they also rated smoking
      satisfaction. Analysis of variance indicated that nicotine played an important
      sensory role for a variety of dimensions related to cigarette taste and sensory
      impact but not perceived draw. Principal-components analyses indicated that
      sensory factors were at least as important as nicotine pharmacology (indirectly
      indexed by the pre-to post-smoking rise in blood nicotine concentration) when
      considering smoking's overall effects on satisfaction, product acceptance, and
      reduction in desire to smoke.

PMID- 8880943
TI  - Increased levels of extracellular noradrenaline in the frontal cortex of rats
      exposed to naturalistic environmental stimuli: modulation by acute systemic
      administration of diazepam or buspirone.
AB  - In vivo microdialysis was used to investigate the effects of an IP injection of
      diazepam or buspirone (each at 3 mg/kg) on spontaneous efflux of noradrenaline in
      rat frontal cortex, and on changes in efflux induced by naturalistic stress.
      After drug administration, rats either remained in their home cages or were
      transferred individually to a novel cage, 1 h later. The novel cage was brightly
      lit (1500 lux) and contained another, unfamiliar rat. After transfer to the novel
      cage, noradrenaline efflux was lower in diazepam-injected rats than in their
      vehicle-injected counterparts. However, in both cases, stress caused a
      significant increase in efflux and the net increase was not affected by diazepam.
      Similarly, buspirone, which increased spontaneous efflux of noradrenaline, did
      not affect the net increase in efflux during stress. Neither compound modified
      locomotor activity in the novel cage. This suggests that any changes in
      noradrenaline efflux are unrelated to drug effects on non-specific arousal. It is
      concluded that generically unrelated anxiolytic agents can have different effects
      on spontaneous efflux of noradrenaline but do not modify the noradrenergic
      response to naturalistic stimuli.

PMID- 8880945
TI  - Effects of lorazepam and diazepam on conscious and automatic memory processes.
AB  - Recent studies exploring benzodiazepine memory effects have used the distinction
      between explicit and implicit tasks. There is now increasing evidence that
      implicit tasks can be "contaminated" by conscious uses of memory and that
      unconscious (automatic) use of memory can contaminate explicit tasks, leading to
      mistaken estimates of their respective influences on memory performance. The aim
      of the present double-blind, double-placebo study was to assess the memory
      effects of diazepam and lorazepam using a process-dissociation procedure in a
      stem-completion task, this procedure providing uncontaminated estimates of
      conscious and automatic memory processes. The memory task was administrated to 60
      healthy volunteers randomly assigned to one of three parallel groups (placebo,
      diazepam 0.3 mg/kg, lorazepam 0.038 mg/kg). Lorazepam markedly reduced conscious
      as well as automatic influences of memory. Diazepam also reduced conscious uses
      of memory, albeit to a lesser extent than lorazepam, but did not decrease the
      influence of automatic memory. Secondary analyses showed that when the
      deleterious effect on conscious uses of memory was equated between a diazepam
      subgroup and the lorazepam group, only lorazepam impaired the automatic use of
      memory. This study strongly suggests a qualitative difference in the memory
      effects of the two benzodiazepines. It has some implications regarding the
      relationships between states of consciousness and memory processes.

PMID- 8880947
TI  - Drug-induced pulmonary hypertension: must history repeat itself?

PMID- 8880946
TI  - The effects of paroxetine given repeatedly on the 5-HT receptor subpopulations in
      the rat brain.
AB  - Effects of paroxetine (10 mg/kg PO, twice daily, 14 days) on 5-HT receptor
      subpopulations in the brain were evaluated pharmacologically,
      electrophysiologically and biochemically in male Wistar rats. Imipramine was used
      for comparison. Repeated paroxetine antagonized the 8-OH-DPAT-induced behavioural
      syndrome (a 5-HT1A effect); imipramine showed similar, yet weaker, activity. The
      5-HT-or 8-OH-DPAT-induced inhibition of population spikes in hippocampal slices
      was increased by both those repeated antidepressants. Repeated (or acute)
      paroxetine decreased the density of and increased the affinity for 5-HT1A
      receptors ([3H]-8-OH-DPAT used as ligand) in the hippocampus, while imipramine
      induced opposite effects. m-Chlorophenyl piperazine (m-CPP)-evoked exploratory
      hypoactivity, a 5-HT2C effect, was reduced by repeated paroxetine, but not by
      imipramine. Either of the antidepressants given repeatedly antagonized TFMPP
      induced hyperthermia (another putative 5-HT2C effect). 5-HTP-induced head
      twitches (a 5-HT2A effect) were inhibited by repeated paroxetine or imipramine.
      Either antidepressant given repeatedly decreased the density of 5-HT2A receptors
      ([3H]-ketanserin as a ligand) in the brain cortex, but did not change their
      affinity. The present results indicate that paroxetine given repeatedly induces
      secondary changes in 5-HT2 receptors, which lead to reduction of the 5-HT2
      neurotransmission (reduced responsiveness of 5-HT2 postsynaptic receptors). The
      consequences of the secondary changes in 5-HT1A receptors, found here still await
      clarification.

PMID- 8880948
TI  - The endothelins in the pulmonary system.
AB  - Although initial research interest in the ETs was focused on their cardiovascular
      effects, it is now clearly established that these peptides have wide-ranging
      activities in the respiratory track. Importantly, ET-1 is synthesized, stored,
      released and metabolized in the lung, suggesting that these activities may be
      relevant to both physiological function and pathophysiological processes in the
      lung. To the present time, only two ET receptor subtypes have been definitively
      characterized in the lung, namely ETA and ETB receptors, both of which have been
      shown to mediate contraction and mitogenesis in airway smooth muscle from humans
      and animals. However, the possibility that further receptor subtypes might be
      defined from functional, biochemical, and molecular biological studies cannot be
      dismissed. It is apparent that the ETs may have a role to play in the
      pathogenesis of several pulmonary diseases. However, most of the current evidence
      for this falls short of establishing convincing causal associations. Perhaps the
      most convincing data relate to pulmonary hypertension. Although it is too early
      to ascribe a role for the ETs in the pathophysiology of asthma, the preliminary
      data are intriguing. Thus far, research has centered largely on the
      bronchoconstrictor effects of ET-1 in vitro and in vivo. In relation to asthma,
      it is important that future studies should focus increasingly on the effects of
      the ETs in nerves and inflammatory cells. In addition, the effects of chronic
      airway exposure to ET-1 on smooth muscle and fibroblast proliferation is an
      important area for future research. The unequivocal testing of the
      pathophysiological role of the ETs in asthma requires the clinical evaluation of
      potent and selective receptor antagonists for the various ET receptor subtypes.
      It seems likely that these studies will be conducted in the not-too-distant
      future, as compounds which possess the appropriate pharmacological profile become
      available for clinical evaluation. Additionally, ECE-1 and ECE-2 present as
      potentially important targets for therapeutic intervention, although the
      development of selective nonpeptide inhibitors may be some years away.

PMID- 8880949
TI  - Sodium cromoglycate and nedocromil sodium in the therapy of asthma, a critical
      comparison.

PMID- 8880950
TI  - Isolated, electrically-stimulated airway preparations--their use in determining
      beta-adrenoceptor agonist activity.
AB  - We have assessed the suitability of electrically-stimulated superfused
      preparations of guinea-pig trachea, cat trachea and human bronchus for
      investigating the relaxant activity of the beta-adrenoceptor agonist,
      isoprenaline. Superfused strips of guinea-pig trachea, cat trachea and human
      bronchus all contracted in response to electrical stimulation. Guinea-pig trachea
      possesses inherent tone, and in its presence, electrical stimulation caused
      biphasic responses, comprising a modest, transient contraction, usually followed
      by a longer lasting relaxation. Human bronchus also possesses inherent tone, but
      responses were variable, generally monophasic, comprising a transient contraction
      of variable magnitude, but a longer lasting relaxation was occasionally observed
      after the transient contraction. Cat trachea possesses no inherent tone, and
      electrical stimulation of this preparation caused simple monophasic contractile
      responses. On guinea-pig trachea, addition of indomethacin (2.8 microM) abolished
      the inherent tone, and under these conditions, electrical stimulation caused
      monophasic contractile responses similar to those observed in cat trachea. On
      human bronchus, however, indomethacin enhanced inherent tone, which tended to
      uncover or exaggerate any relaxant component in the responses to electrical
      stimulation. The 5-lipoxygenase inhibitor, zileuton (10 microM), reduced, but did
      not abolish, the tone and converted the electrically-induced response to a
      monophasic contraction. In all preparations in which inherent tone was low or
      absent, whether naturally (cat trachea) or through pharmacological intervention
      (guinea-pig trachea with indomethacin, or human bronchus with zileuton),
      isoprenaline (1-100 nM) inhibited electrically-stimulated contractions in a
      concentration-related fashion (EC50s: 9-100 nM). In preparations exhibiting
      inherent tone (guinea-pig trachea with indomethacin or human bronchus with or
      without indomethacin), this tone was inhibited by isoprenaline. This relaxant
      activity, on guinea-pig trachea at least, was concentration-related (EC50: 5.4
      nM). Such isoprenaline-induced relaxations complicated the analysis of inhibitory
      effects against electrically-induced contractions. Thus, in such experiments,
      only at higher concentrations did isoprenaline reliably inhibit these
      contractions (EC50: 23-119 nM), lower concentrations of isoprenaline often
      resulting in an apparent enhancement. The enhancement was probably artefactual,
      resulting from the fact that the electrically-induced contractions originated
      from a lower baseline. These data suggest that electrically-stimulated airway
      preparations are suitable for evaluating the relaxant activity of beta
      adrenoceptor agonists, but the relaxant potency should be assessed in
      preparations lacking inherent tone, such as cat trachea, guinea-pig trachea in
      the presence of cyclo-oxygenase inhibition, or human bronchus in the presence of
      5-lipoxygenase inhibition.

PMID- 8880951
TI  - Effect of chronic glutathione deficiency on rat lung mitochondrial function.
AB  - The effect of chronic glutathione deficiency on lung mitochondrial energy
      production using buthionine sulphoximine (BSO) as a depletor has been
      investigated. Prolonged depletion of mitochondrial glutathione produced an
      imbalance in the antioxidant defence and resulted in lipid peroxidation, which,
      in turn, damages the membranous structure, leading to the inactivation of inner
      membrane enzymes, matrix-bound enzymes and mitochondrial cytochrome content.
      Altered activities of energy-linked enzymes and electron transport resulted in
      the decreased rate of ADP-stimulated oxygen uptake, respiratory coupling ratio
      and ATP synthesis.

PMID- 8880952
TI  - The effect of oxygen tension on responses evoked by methacholine and
      bronchodilators in bovine isolated bronchial rings.
AB  - This study examined the effect of acute changes in oxygen tension on responses
      evoked by the bronchoconstrictor methacholine and the dilators salbutamol, atrial
      natriuretic peptide and isosorbide dinitrate in isolated bovine bronchi.
      Cumulative concentration-response curves to methacholine (10(-9)-3 x 10(-4) M)
      were constructed in three oxygen tensions; hyperoxia (95%), normoxia (20%) and
      hypoxia (4% O2). Oxygen tensions of 20% and 4% each significantly enhanced
      contractions to methacholine compared to those in 95% O2. There was no
      significant difference, however, between responses in 20 and 4%. The ability of
      salbutamol, atrial natriuretic peptide and isosorbide dinitrate to reverse
      methacholine induced tone was also compared in the three oxygen tensions (95%,
      20% and 4%). Lowering the oxygen tension from 95% enhanced the ability of each of
      the drugs to reverse contraction, however the pattern differed between drugs;
      salbutamol was more effective in 20% O2 than 4%, atrial natriuretic peptide was
      more effective in 4% than either 95 or 20% O2 and isosorbide dinitrate was more
      effective in both 4 and 20% than 95% O2. In conclusion, both bronchoconstrictor
      and bronchodilator responses in 95% O2 (hyperoxia) differed from those in 20% O2
      (normoxia) and further changes occurred on moving to 4% (hypoxia), although the
      direction of the changes varied among the dilators. This suggests that the
      responses evoked by bronchodilators in 95% O2 may not necessarily predict those
      in the physiological range of oxygen tensions and that the relative effectiveness
      of bronchodilators may vary between normoxic and hypoxic conditions.

PMID- 8880953
TI  - Investigating causation in cancer clusters.
AB  - Questions concerning clusters of cancer cases frequently arise in public health
      practice. The process of investigating any such cluster requires awareness that
      such case groupings can easily occur by chance and that any search for
      biologically meaningful causes will be severely constrained by various
      methodologic difficulties. These include (1) the long and probably variable
      latent periods between causative events and cancer diagnosis, (2) the limited
      numbers of cases available for study in any given cluster situation, and (3) the
      clinical non-specificity of cancer cases whereby no readily available means are
      at hand to identify the specific causes for any particular case. Evaluation of
      any given cluster should involve careful consideration of such limitations,
      together with a preliminary assessment of the specific cases involved and their
      community or workplace setting, before more intensive study is undertaken.

PMID- 8880954
TI  - Use of subjective and nonsubjective methodologies to evaluate lens radiation
      damage in exposed populations--an overview.
AB  - The general epidemiological acceptability of prevalence, or incidence, for
      assessing risk of radiation cataract development has dictated an almost exclusive
      dependence on cataract onset as a measure of cataractogenicity for given doses of
      radiation. The advent of instrumentation capable of acquiring images amenable to
      quantitative analyses offers the possibility of exploiting "relative
      opacification" as an added, if not exclusive, parameter. This development is
      particularly important in efforts to assess populations such as that in the
      Altai, which are temporally far removed from their exposure and among whom there
      exists a large subset with extant cataracts. The new technologies, Scheimpflug
      and retroillumination imaging, combined with the application of the appropriate
      analytical algorithms can not only provide quantitative and nonsubjective
      assessment of lens transparency, but also serve as a means to immortalize the
      state of the pathology at the time of acquisition. Highly relevant to the
      assessment of an aging exposed population is the use of lens epithelial fragments
      as potential dosimeters. The material is routinely available as a result of
      cataract extraction procedures and is amenable to the application of a modified
      micronucleus (MN) assay. The MN assay in the lens has tremendous advantages over
      its use in other tissues for a number of reasons, not least of which is that lens
      MNs are extremely long-lived. Given the relative ease of application and its
      potential as a radiation bioindicator, the lens MN assay should be considered in
      any follow-up of populations exposed to ionizing radiation.

PMID- 8880955
TI  - Generalization of the variance-covariance method for microdosimetric
      measurements. III. Numerical simulation to assess the applicability of the
      formulae.
AB  - Numerical simulations in terms of microdosimetric data for 5-MeV neutron are
      utilized to test the twin detector method of microdosimetric measurements in its
      new, extended form. Three different conditions of measurement are considered: (I)
      constant dose increments per measurement, (II) fluctuating dose increments per
      measurement, and (III) fluctuating dose increments combined with slow changes of
      the dose-rate ratio for the two detectors. Under each of the conditions, large
      numbers of measurement series are simulated, and the estimation formulae for the
      mean and the two subsequent moments of the dose-weighted single-event
      distribution, d(y), are applied. The estimation formulae exist in three different
      forms: uncorrected formulae that apply to condition I, corrected formulae that
      are valid also for condition II, and fully corrected formulae that remain
      applicable under condition III. The results of the simulations indicate the
      acceptable ranges of doses per measurement interval. It can be seen that all
      three parameters are obtainable through the twin detector method, and that the
      fully corrected formulae for the two lower moments are generally applicable. The
      determination of the third moment is possible only under limited conditions, and
      the fully corrected formula is not useful in this case, while the corrected
      formula has some applicability even under condition III.

PMID- 8880956
TI  - Energy spectra of secondary electrons in water vapour.
AB  - The purpose of this work is to present a method for the calculation of secondary
      electron spectra generated by photons in water vapour in the energy region from
      10 eV to 10 MeV. The cross sections below and above 1 keV have been treated
      separately. Examples are given for secondary electron spectra for low-energy
      photons, < 100 eV, in which all electrons are photoelectrons, and at higher
      energy regions, such as for 60Co photons. The spectrum of the first generation of
      secondary electrons, produced by 60Co photons, which are mainly due to incoherent
      scattering, was fitted with a set of polynomial functions which can be used as
      input for electron radiation action calculations.

PMID- 8880957
TI  - High-energy electron irradiation of proteins and nucleic acids: collisional
      stopping power and average energy loss.
AB  - Inactivation of proteins due to the direct action of ionizing radiation and the
      electron energy loss spectra of organic materials indicate that an average of 60
      66 eV of energy is lost from high energy electrons in each inelastic collision
      with target molecules. The average energy loss per inelastic collision with high
      energy electrons in solid, carbon-based materials, proteins and nucleic acids is
      calculated from mass collisional stopping powers and empirical total inelastic
      cross-sections. Bragg's Additivity Law is used for the calculation of the mean
      excitation energy of molecules. For simple organic compounds, the calculated
      average energy loss is close to that obtained by direct observation of the energy
      loss suffered by electrons as they pass through thin films of organic material.
      The density effect correction for the rate of energy loss, important in the more
      complex case of proteins irradiated with 10 MeV electrons, is determined using
      the comparable mass collisional stopping power of water and proteins. In this
      manner, a value is obtained for the average energy per inelastic collision of
      high energy electrons with proteins, which is similar to the average energy per
      inactivating event of proteins. Analogous calculations for nucleic acids are also
      presented.

PMID- 8880958
TI  - Two types of double-strand breaks in electron and photon tracks and their
      relation to exchange-type chromosome aberrations.
AB  - Yields of DNA double-strand breaks (dsb), i.e. the average number of dsb, N, per
      relative molar mass, M(r), and dose, D, produced by electrons and photons in the
      energy range 50 eV-1 MeV were calculated. The experimental data of dsb induction
      by ultrasoft x-rays and by photons agree well with the calculated yields of dsb
      as a function of photon energy. The dsb are classified into simple and complex
      ones. Energy transfers of less than about 200 eV producing at least two
      ionizations generate mainly simple dsb, while low-energy electrons with an
      initial energy between 200 and 500 eV induce preferentially complex dsb. Assuming
      that dsb is the main DNA lesion leading to exchange-type chromosome aberrations
      (etca), three different mechanisms have to be considered: 1) complex dsb on its
      own; 2) interaction between two dsb induced by the same primary particle; and 3)
      interaction between two dsb induced by different primary particles. Mechanisms 1)
      and 2) produce a linear term, whereas mechanism 3) leads to a quadratic term for
      the yield of etca. The sum of contributions 1) and 2) to the yield of dicentrics
      describes fairly well the non-trivial structure of the experimental data. The
      results suggest that interaction between complex dsb does not contribute
      significantly to the formation of dicentrics via mechanism 3).

PMID- 8880959
TI  - Complex repair kinetics of DNA strand breaks induced by gamma-rays of UV
      radiation in Ehrlich ascites tumour cells.
AB  - Fluorometric analysis of DNA unwinding (FADU)-a sensitive technique for the
      detection of strand breaks in DNA-has been modified and used for the detailed
      investigation of repair kinetics of DNA-strand breaks arising under different
      conditions in Ehrlich ascites tumour (EAT) cells irradiated by gamma-rays or
      ultraviolet (UV) radiation. The repair kinetics of DNA-strand breaks induced in
      EAT cells by gamma-radiation was measured at radiation doses of 8, 20 and 50 Gy.
      We found complex repair curves in all cases, probably reflecting the combined
      processes of break rejoining and break generation during repair. In order to
      affect the above-mentioned processes, we have used different conditions of repair
      and different types of radiation. Lowering of the temperature of incubation and
      treating the cells by 5-fluoro-2'-deoxyuridine (FUdR) lead to complex changes of
      the repair curve with a reduced "wave" pattern. In order to change the type of
      damage to DNA, we used UV radiation (254 nm, 10 and 20 J/m2). Detailed studies of
      the repair kinetics showed that the repair curve for 10 J/m2 had a second maximum
      within 70 min after irradiation.

PMID- 8880960
TI  - Analysis of chromosome aberrations in human peripheral lymphocytes induced by in
      vitro alpha-particle irradiation.
AB  - Irradiation of human lymphocytes by alpha-particles under different conditions
      has been seen to be substantially more effective in the induction of dicentric
      chromosomes than irradiation by gamma-rays. However, the relative biological
      effectiveness (RBE) determined in these studies differed by a factor of more than
      10. These variations in RBE are likely to be due in part to differing exposure
      conditions. Therefore, a technique designed to insure uniformity of irradiation
      was developed in the present study, and complications due to the cell cycle
      kinetics were controlled. After stimulation with phytohaemagglutinin (PHA),
      separated lymphocytes were allowed to attach for 3 h to the thin foil bottom of
      an irradiation chamber. Cell monolayers were exposed with alpha-particles from
      Am. Strong over-dispersion was noted for the cell-to-cell variance of the number
      of dicentrics. The dose response of dicentrics was linear, with a yield of 0.27
      dicentrics per cell and per Gy. This corresponds to a low dose RBE of 15 relative
      to Cs gamma-ray exposure under the same experimental conditions.

PMID- 8880961
TI  - Modulation of the effect of camptothecin in x-irradiated L5178Y-R and L5178Y-S
      cells by benzamide.
AB  - The L5178Y (LY) murine lymphoma subline, LY-R, is more radioresistant and more
      sensitive to camptothecin (CPT, inhibitor of topisomerase I) than the second
      subline used in our investigation, LY-S. Post-irradiation treatment with 3 microM
      CPT enhanced the radiosensitivity of LY-S cells (D0 decrease from 0.52 to 0.34
      Gy), but did not change it in LY-R cells. Treatment with 2 mM benzamide [BZ,
      inhibitor of poly (ADP-ribosylation)] before x-rays and CPT increased the
      radiosensitivity of LY-R cells (D0 decrease from 1.15 to 0.52) without further
      modification of radiosensitivity of LY-S cells. Activity of topoisomerase I was
      diminished 10 min after x-irradiation (5 Gy) in LY-S, but not in LY-R cells. The
      data on DNA damage (fluorescent halo or comet assays) showed that the ultimate
      fate of the cells did not depend on the DNA damage pattern estimated immediately
      after treatment (e.g. the damage was greater in x-rays plus CPT than in BZ plus x
      rays plus CPT treated LY-R cells, although the radiosensitivity was less).
      Aphidicolin (inhibitor of DNA polymerases alpha and delta) applied concomitantly
      with CPT in cells not pretreated with BZ prevented the increase in DNA damage in
      LY-R cells, but was without effect in LY-S cells. Taking into account the
      differential inhibition by x-rays of DNA synthesis in LY sublines and its
      reversion by BZ in LY-S but not in LY-R cells, we conclude that the pattern of
      DNA damage observed by the methods applied depended on the status of DNA
      replication.

PMID- 8880963
TI  - Influence of 50-Hz electric and magnetic fields on human blood pressure.
AB  - This investigation studied the effects of 50-Hz electric and magnetic fields on
      the pulse rate and blood pressure in humans. Electrocardiograms (ECG) and the
      blood pressure of 41 male volunteers were recorded using ambulatory methods.
      Twenty-six subjects were measured in and outside real fields and 15 subjects in
      and outside "sham' fields. The results of the ECG recordings have been presented
      earlier. This article deals with the analysis of the blood pressure measurements.
      Measurement took 3 hrs. First, the subjects spent 1 h outside the fields, then 1
      h in real or "sham' fields, followed by 1 h outside the fields. The electric
      field strength varied from 3.5 to 4.3 kV/m and the magnetic flux density from 1.4
      to 6.6 microT. When analysing the blood pressure, which was measured with a
      noninvasive cuff method, it could not be shown that the fields (< 4.3 kV/m and <
      6.6 microT) affected diastolic or systolic blood pressure.

PMID- 8880962
TI  - Lack of protection by carotenes against gamma-radiation damage in Phycomyces.
AB  - Carotenes could protect cells from radiation damage by chemically quenching the
      free radicals and the activated chemical species originated by the exposure. We
      tested this hypothesis with strains of the zygomycete Phycomyces blakesleeanus
      that contained different carotenes (phytoene, lycopene, beta-carotene) or
      different concentrations of beta-carotene. Pairs of strains were cultured
      together, exposed to a maximum of 73 Gy gamma-radiation from a Co source, and
      allowed to recover and grow further together on limited resources. Irradiation
      did not affect the relative abundance of each strain in the resulting spore crop.
      Thus, carotenes did not protect the fungal cells against gamma-radiation and did
      not influence their recovery from damage caused by the exposure.

PMID- 8880964
TI  - Radiation exposure from radionuclides in ground water: an uncertainty analysis
      for selected exposure scenarios.
AB  - The uncertainty of the potential radiation exposure of the general population has
      been estimated for a normalized contamination of ground water that is being used
      as drinking water for humans and animals, for irrigation of food and feed crops,
      and for fish production in freshwater bodies. The frequency distributions of
      annual effective dose equivalents were calculated assuming a normalized activity
      concentration in water of 1 Bq/l for each radionuclide considered. Estimated
      frequency distributions of the parameters were used as model input. This
      estimation is based on an exposure scenario which reflects the present
      radioecological conditions. Another important source for the uncertainty of the
      potential dose due to radionuclides released to the ground water is the
      uncertainty of the exposure scenario. Since such a contamination may not occur
      before some time in the far future, it is impossible to predict the exact
      boundary conditions. Therefore, scenarios were stimulated with modified
      consumption habits, more extensive farm management and different climatic
      conditions. The distributions of the potential doses cover in general about a
      factor of 10-20. The intake of drinking water, the root uptake and the
      contamination of fish are most important for the resulting potential radiation
      exposure. For nearly all radionuclides, the intake of drinking water dominates
      the potential exposure. In most cases radioactive daughter nuclides are of minor
      importance. In general, the influence of the exposure scenario on the dose is
      relatively small.

PMID- 8880965
TI  - Nuclear waste repositories in salt mines: a new approach to safety assessment.
AB  - The long-term safety of radioactive waste repositories in rock-salt mines in the
      deep underground benefits significantly from the barrier effect of overlying
      rocks. The concentrations of radioactive substances released from the repository
      and migrating in the aquifer up to the biosphere are greatly reduced during
      passage through these rocks. In former safety analyses of waste repositories this
      transport has generally been modelled as a combination of the involved phenomena,
      e.g. convection, dispersion, adsorption, etc. The data required for a numerical
      evaluation of the overall effect are obtained either as (conservative) estimates
      based on experience or are empirical, based mainly on laboratory experiments. The
      approach presented here is much simpler and entirely empirical, and therefore
      more transparent. It makes use of the fact that the groundwater in the overlying
      rocks always contains dissolved salt from the salt formation and carries it
      continuously into the receiving channels or the drainage system. The relation
      between the total amount of dissolved solids present in a certain subsurface
      catchment area and their steady-state concentration in the receiving channels is
      assumed to be equivalent to the relation between the given amount of
      radionuclides released from the repository and their concentration in the
      receiving channels, the latter leading to a certain radiation exposure of the
      population. Two versions of this approach are discussed: version (a) assumes a
      continuous stream of radionuclides released from the repository, and version (b)
      assumes a pulse release of radionuclides from the repository. A simple
      calculation using data from the Gorleben exploration leads to the inequality
      [equation: see text] where Cmax is the maximum radionuclide concentration (with
      respect to time) in the receiving channels and W (Bq) is the amount of
      radionuclides released from the respository in a very short time. Cmax obtained
      from (1), is supposed to be an upper limit of the radionuclide concentration in
      the receiving channel and, therefore, a conservative estimate. In some catchment
      areas the salt concentration in a small region near the surface is higher by a
      factor of < 2 to 3 than the concentration in the receiving channel. In order to
      be conservative, this empirical factor may be used to calculate the concentration
      of radioactive substances. Surprisingly, the values of radiation exposure
      resulting from both versions of the new approach are far below those calculated
      by applying elaborated models of the transport processes. The respective factors
      are 10-100 in case (a) and as much as 1000 in case (b). The reasons for these
      significant differences are discussed.

PMID- 8880966
TI  - Association of fallout radiocesium with soil constituents: effect of
      sterilization of forest soils by fumigation with chloroform.
AB  - The effect of soil sterilization by chloroform fumigation on the release of
      fallout radiocesium incorporated in the fungal biomass of the organic layer of
      two forest soils was investigated by applying a sequential extraction procedure
      for radiocesium. The amount of the biomass in all soil samples was estimated by
      determination of the dissolved organic carbon (DOC) before and after fumigation,
      and qualitatively also by the ergosterol test. The five fractions obtained by
      sequential extraction (modified Tessier procedure) were: (I) easily exchangeable,
      (II) bound to oxides, (III) bound to organic matter, (IV) persistently bound, (V)
      residual. For the samples from the soil under spruce trees, no significant
      effects were apparent in any of these five fractions as a result of chloroform
      fumigation, indicating that the amount of radiocesium in the biomass of this soil
      was obviously negligibly small compared with the radiocesium associated with
      other soil constituents. The results obtained for the soil samples from the beech
      stand, however, reveal that the destruction of the biomass by chloroform
      fumigation modified considerably the extent of the association (i.e., binding) of
      radiocesium with the various other soil constituents (especially the clay
      minerals). As a result of this rapid redistribution of radiocesium released by
      the fungal biomass, it is not possible, in general, to attribute the observed
      increase of radiocesium in fraction I (easily exchangeable) after soil
      sterilization quantitatively to radiocesium released by the biomass. A reliable
      method to determine the amount of radiocesium incorporated in the fungal biomass
      of the soil samples which also contain clay minerals has, therefore, still to be
      developed.

PMID- 8880967
TI  - Using compensating filters to reduce radiation dose.
AB  - The study described in this article explores the role of compensating filters in
      reducing radiation exposure. Radiation exposure levels with and without filters
      were compared in skull radiographs, hepatic angiographs and one-shot full-length
      lower extremity radiographs. Absorbed doses were measured with and without a
      skull filter in a phantom at a depth of 5 cm. Results showed that filters reduced
      exposure by 29% in skull radiographs, 47% in hepatic angiographs and 80% in one
      shot full-length lower extremity radiographs. Absorbed doses were reduced by more
      than 26% in the skull phantom in the filtered area. To reduce patient dose, the
      filters were positioned between the x-ray tube and the patient.

PMID- 8880968
TI  - Elder abuse: the R.T.'s role in diagnosis and prevention.
AB  - During the course of their jobs, radiologic technologists may encounter older
      patients who are the victims of abuse. In addition to their role in aiding with
      diagnosis, radiologic technologists can help in the prevention of elder abuse
      through an understanding of their ethical and legal obligations and good patient
      assessment skills. Although health care professionals may be legally mandated to
      report abuse, a complicating factor is the right of the elderly patient to self
      determination. This article outlines some of the factors used in determining
      whether abuse should be suspected and reported.

PMID- 8880969
TI  - An Australian model for professional standards.
AB  - This article describes the qualitative research methodologies used to develop
      entry-level standards documents for the four medical radiations science
      professions in Australia. This Australian model features a mix of complementary
      research tools to validate the range and level of the professional standards. In
      addition to methodology, this article also describes the beneficial role played
      by these standards and the possibility of using the development method in other
      countries.

PMID- 8880970
TI  - Epidemiology, diagnosis and treatment of prostate cancer.
AB  - Prostate cancer is the most commonly diagnosed cancer in the United States. This
      article outlines the anatomy of the prostate gland, the epidemiology and natural
      history of prostate cancer, current diagnostic and screening techniques,
      treatment options and prognostic implications.

PMID- 8880971
TI  - Educational trends in the radiologic sciences. Results of a validation research
      survey.
AB  - This special report examines the results of a validation research survey
      conducted to assess ASRT members' opinions regarding future educational
      requirements for radiologic technologists as well as satisfaction with their own
      educational training. Results of the survey were compared to recommendations made
      by participants of the profession's first Educational Consensus Conference to
      measure the level of agreement. Comparison showed a strong degree of agreement in
      most areas.

PMID- 8880972
TI  - A core curriculum for health professions.

PMID- 8880973
TI  - Certification standards, Part 3: Examination.

PMID- 8880975
TI  - But for one key factor....

PMID- 8880974
TI  - Students' expectations of clinical teachers.
AB  - Clinical instructors play an essential role in the education of all health care
      students, including radiation therapy students. However, a review of the
      literature shows that no studies have examined radiation therapy students'
      expectations of their clinical instructors. To assess those expectations, a
      national survey was conducted of 282 radiation therapy students enrolled in 61
      programs in 28 states. Survey results then were analyzed to generate a list of
      the students' expectations of clinical instructors and to look at possible
      significant relationships between the various groups surveyed. Survey results
      showed that the most common expectation among first-, second- and third-year
      radiation therapy students was that their clinical instructors "take time, both
      in explaining procedures and answering questions." Among fourth-year students,
      the most commonly cited expectation for clinical instructors was that they "model
      professionalism."

PMID- 8880976
TI  - Biosynthesis of B2-integrin, intracellular calcium signalling and functional
      responses of normal and CD18-deficient bovine neutrophils.
AB  - 1Biosynthesis of CD11/CD18 in bovine leucocytes, intracellular Ca2+ ([Ca2+]i)
      signalling, chemiluminescent responses and membrane fluidity of neutrophils and
      the effects of D-mannose on neutrophils from control heifers and a heifer with
      bovine leucocyte adhesion deficiency (BLAD) were measured. The synthesis of
      CD11/CD18 complex was clearly detected in leucocytes from a normal heifer, but
      not in a BLAD-affected heifer. The transient phase of increased [Ca2+]i was
      clearly detected in neutrophils from a heifer with BLAD stimulated with opsonised
      zymosan, aggregated bovine immunoglobulin G or concanavalin A, whereas the
      sustained phase was deficient or significantly decreased compared with control
      heifers. [Ca2+]i signalling of neutrophils from control heifers and a heifer with
      BLAD stimulated with phorbol myristate acetate via an 11b/CD18-independent
      pathway showed no transient phase, and the subsequent increase in [Ca2+]i was
      almost identical in neutrophils from affected and control heifers. [Ca2+]i
      concentration and chemiluminescent responses of neutrophils from a control heifer
      were clearly decreased by treatment with anti-CD18 and anti-IgG antibodies. No
      differences in membrane fluidity were detected between neutrophils derived from
      control and CD18-deficient cattle. D-mannose binds mainly to Fc rather than CD18
      receptors, and decreased Agg-IgG induced [Ca2+]i and the chemiluminescent
      response of neutrophils. The [Ca2+]i responses and Agg-IgG induced
      chemiluminescent responses of neutrophils from control heifers and a BLAD
      affected heifer were inhibited by D-mannose. The characteristic changes of
      [Ca2+]i signalling and functional responses of B2-integrin-deficient neutrophils
      were demonstrated.

PMID- 8880978
TI  - Effects of platelet activating factor on the distribution of radiolabelled
      leucocytes and platelets in normal horses and asymptomatic horses with chronic
      obstructive pulmonary disease.
AB  - Antigen challenge is known to cause the recruitment of neutrophils to the lungs
      of horses with chronic obstructive pulmonary disease (COPD). To evaluate a
      possible role of platelet activating factor (PAF) in this process, the effects of
      PAF on the distribution of radiolabelled neutrophils were compared in normal
      horses and asymptomatic horses with COPD. Changes in lung function, heart rate
      and the distribution of platelets and eosinophils were also measured. PAF (5 ng
      kg-1 intravenously) caused immediate but transient increases in the number of
      radiolabelled neutrophils in the lungs and a concomitant decrease in the
      peripheral neutrophil count. The total numbers of circulating leucocytes and
      neutrophils were also significantly decreased by PAF. Rapid and reversible
      increases in heart rate, respiratory rate and pleural pressure were also
      observed. In separate experiments, the numbers of radiolabelled eosinophils and
      platelets in the lungs increased transiently after the administration of PAF. The
      responses to PAF were qualitatively and quantitatively similar in normal horses
      and asymptomatic COPD horses. The PAF receptor antagonist WEB2086 (3 mg kg-1
      intravenously) inhibited the effects of PAF. These results suggest that PAF, if
      released in the lungs of horses with COPD during an antigen challenge, might
      contribute to the recruitment of leucocytes and the respiratory changes.

PMID- 8880977
TI  - Echinococcus granulosus antigen B and seroreactivity in natural ovine
      hydatidosis.
AB  - Hydatid cyst fluid from sheep and camels infected with Echinococcus granulosus,
      together with partially purified preparations of hydatid fluid antigen B and a
      recombinant antigen B product, were tested in an ELISA for their ability to
      detect IgG antibodies against E granulosus in the serum of naturally infected
      sheep. The antibody activity in sera from sheep naturally infected with Taenia
      hydatigena cysticercosis or Fasciola hepatica was also tested. All the antigen
      preparations from native hydatid cyst fluid were able to detect antibodies in the
      sera from a significant proportion of sheep with natural hydatid cyst infection,
      as identified by inspection at slaughter, although the seroreactivity was
      variable. The native antigen B preparation from camel hydatid cyst fluid gave the
      highest sensitivity in the ELISA (total 90 per cent), with 99 per cent
      specificity. In all cases, the recombinant antigen B was the least sensitive
      antigen (25 per cent) although it was highly specific (99 per cent).

PMID- 8880979
TI  - Tumour suppressor gene p53 in the horse: identification, cloning, sequencing and
      a possible role in the pathogenesis of equine sarcoid.
AB  - The tumour suppressor protein p53 enhances the genetic stability of the cell and
      plays a critical role in tumour suppression. Equine p53 was analysed by
      sequencing exons 5 to 9, a region which includes most known mutations and all the
      mutational hotspots in the species that have been investigated. The fragment was
      amplified, cloned and sequenced from genomic and complementary DNA. A comparison
      of the predicted amino acid sequences between the horse and other species
      resulted in identities between 66 per cent with the clawed frog and 92 per cent
      with the cat. Using the single strand conformation polymorphism technique, exons
      5 to 8 amplified from sarcoid tissue and peripheral leucocytes of 28 sarcoid
      affected and 11 healthy horses were screened for mutations. No mutations were
      identified, suggesting that the frequency of p53 mutations in equine sarcoid
      might be low. However, the high incidence of bovine papillomavirus (BPV)
      infection in equine sarcoid may indicate the functional inactivation of p53 by
      BPV-encoded E6 protein.

PMID- 8880980
TI  - Expression of the gene for transforming growth factor-beta in avian
      dyschondroplasia.
AB  - Previous immunolocalisation studies of dyschondroplasia have indicated that there
      is a reduction in the number of growth plate chondrocytes containing the protein
      transforming growth factor beta 3 (TGF-beta 3). The reduction in TGF-beta 3 in
      dyschondroplasia is likely to be a direct result of a reduction in the expression
      of the TGF-beta 3 gene. mRNA was extracted from small (0.09 g) samples of growth
      cartilage from the proximal tibiotarsus of three-week-old broiler chicks. The
      cartilage samples contained cells from all three zones of the growth plate
      (proliferative, transitional and upper hypertrophic) and were collected from
      normal and dyschondroplastic growth plates. The dyschondroplastic growth plates
      were identified by an accumulation of transitional chondrocytes which were
      considered to be a result of a failure to differentiate to the hypertrophic
      phenotype. A semi-quantitative polymerase chain reaction (PCR) was used to
      estimate the quantity of mRNA specific for glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and for each of the three isoforms of TGF beta (TGF-beta 1,
      TGF-beta 2 and TGF-beta 3) in each of the cartilage samples. The levels of
      expression of mRNA for GAPDH, TGF-beta 1 and TGF-beta 2 were similar in the two
      groups, but the expression of TGF-beta 3 mRNA was significantly reduced in the
      samples from the dyschondroplastic growth plates. The reduction in TGF-beta 3
      levels is thought to be associated with the failure of chondrocyte hypertrophy in
      dyschondroplasia, and provides in vivo evidence that TGF-beta 3 is part of the
      cascade of events associated with the differentiation of chondrocytes during
      endochondral ossification in the chick.

PMID- 8880981
TI  - Volume assessment of the bovine hoof.
AB  - The size of bovine hooves is one factor that may affect their ability to absorb
      shock. An increase in size could therefore reduce the risk of lameness associated
      with excessive digit loading. The hooves of 30 mature cattle were assessed by
      linear measurements with the objective of predicting digit volume, which was
      measured separately by water displacement. Claw volume was predicted accurately
      by regression equations including the top hoof width, toe length and heel angle.
      Replacing toe length and heel angle with the age and weight of the animal also
      gave an acceptable prediction and would be more appropriate for on-farm
      measurement. A reasonable prediction could be obtained from the top hoof width
      alone. Front hooves were larger and had greater heel depth than hind hooves. In
      26 of the cattle either the right fore and left rear hooves, or the left fore and
      right rear hooves, were larger than the other two hooves, indicating that crossed
      limb laterality (symmetry in diagonally opposed limbs) may be present to a
      greater degree than has been previously recognised in quadrupeds.

PMID- 8880982
TI  - IgG subclasses of canine anti-erythrocyte, antinuclear and anti-thyroglobulin
      autoantibodies.
AB  - A panel of monoclonal antibodies (mAbs) reactive with the four canine IgG
      subclasses (IgG1, IgG2, IgG3 and IgG4) was used to investigate the activity of
      IgG subclasses in autoimmune responses to erythrocytes, nuclear antigens and
      thyroglobulin in dogs with autoimmune disease. mAbs specific for canine IgG1 and
      IgG4 were able to agglutinate normal dog erythrocytes coated with purified canine
      IgG containing each of the four subclasses. IgG1 autoantibodies were demonstrated
      on the surface of erythrocytes from seven dogs with Coombs'-positive autoimmune
      haemolytic anaemia and IgG4 autoantibodies were also present in two of these
      cases. Serum antinuclear antibody was shown in nine dogs to be predominantly of
      IgG1, IgG3 and IgG4 subclasses with only one of the dogs also producing an IgG2
      antinuclear antibody. The IgG subclass profile of antinuclear antibodies differed
      between dogs with polyarthritis and dogs with other systemic disease. In six dogs
      with hypothyroidism, thyroglobulin autoantibodies of subclasses, IgG1, IgG2 and
      IgG4 predominated, but one dog also produced significant levels of IgG3
      thyroglobulin autoantibodies. The mAbs are widely applicable to the study of the
      pathogenesis of canine autoimmune disease.

PMID- 8880983
TI  - Subclass profile of allergen-specific IgG antibodies in atopic dogs.
AB  - Levels of allergen-specific IgE and IgE antibodies were determined in serum
      samples from 60 atopic and 11 normal dogs by means of commercially available
      ELISA test kits and a panel of 33 allergens. In the atopic population, IgE
      antibodies were most commonly identified with a specificity for Dermatophagoides
      farinae (78.3 per cent of affected dogs), D pteronyssinus (61.6 per cent), mould
      mix (25 per cent) and house dust (19 per cent), whereas the most frequently
      detected IgG antibodies had a specificity for D farinae (38.3 per cent), D
      pteronyssinus (33.3 per cent), mould mix (33.3 per cent), insect mix (16.6 per
      cent) and meadow fescue (16.6 per cent). The IgG subclass profile of allergen
      specific antibodies was determined for five representative allergens from the
      panel. The IgG response to D farinae and D pteronyssinus was dominated by IgG4
      antibodies, although lower levels of IgG2, and IgG3 and IgG1 D pteronyssinus
      antibodies were also detected. The IgG response to Timothy grass was
      predominantly within the IgG1 and IgG4 subclasses, IgG subclass selection in the
      response to mould mix and insect mix was broader, with relatively low level
      reactions from all four subclasses. The data suggest a degree of IgG subclass
      restriction in the humoral immune response of canine atopy which may be dependent
      upon the nature of the allergen.

PMID- 8880984
TI  - Single-dose pharmacokinetics of ampicillin/sulbactam (2:1) combination after
      intravenous administration to sheep and goats.
AB  - The pharmacokinetic behaviour of a combination of ampicillin and sulbactam (2:1)
      in six sheep and six goats after single intravenous doses of 20 mg kg body weight
      1 (13.33 mg kg-1 of ampicillin and 6.67 mg kg-1 of sulbactam) was investigated by
      using a high-performance liquid chromatographic method for determining plasma
      concentrations. The objective was to determine whether there are differences
      between sheep and goats in the disposition kinetics of ampicillin and sulbactam.
      The plasma concentration-time curves were analysed by compartmental
      pharmacokinetic and non-compartmental methods. The disposition curves for both
      drugs were best described by a biexponential equation (two-compartment open
      model) in both sheep and goats. The mean (SD) elimination half-lives of
      ampicillin were 0.32 (0.05) h in sheep and 0.32 (0.04) h in goats, and the half
      lives of sulbactam were 0.74 (0.10) h and 0.79 (0.18) h in sheep and goats,
      respectively. The apparent volumes of distribution of ampicillin and sulbactam
      were similar in the two species. Mean (SD) body clearances of ampicillin were
      0.69 (0.07) litre h-1 kg-1 in sheep and 0.72 (0.11) litre h-1 kg-1 in goats, and
      the body clearances of sulbactam were 0.38 (0.03) and 0.38 (0.07) litre h-1 kg-1
      in sheep and goats, respectively. There were no significant differences between
      any of the pharmacokinetic parameters of ampicillin and sulbactam in the sheep
      and goats.

PMID- 8880985
TI  - Improved isolation of Clostridium perfringens from foal faeces.
AB  - There have been several case reports of foal diarrhoea associated with
      Clostridium perfringens. However, there has been no epidemiological assessment of
      the strength of the association of these bacteria with foal diarrhoea or of their
      relative importance. To prepare methods for such a study, the success of
      different cultural techniques for the isolation of C perfringens was examined
      with respect to the various physiological states of the bacteria. The germination
      and growth of C perfringens NCTC 8239 endospores of differing maturity were
      favoured by different pre-treatments which failed to recover vegetative cells or
      endospores of C perfringens NCTC 8237. Faecal samples from 271 foals were used to
      test the hypothesis that the recovery of C perfringens, probably present in
      different states ranging between vegetative cell and germinating endospore, would
      be improved by using several methods in parallel. Five methods (two pre
      enrichment and three direct), using different pre-treatments with heat, ethanol
      and EDTA, or no pre-treatment, together isolated C perfringens from 64 per cent
      of the samples; the most sensitive method (which isolated the most C perfringens)
      detected only 74 per cent of these positive samples. All the methods detected C
      perfringens in at least one sample from which it was not isolated by any other
      method. It was concluded that several methods used in combination on each sample
      would be required to evaluate fully any epidemiological association between C
      perfringens and foal diarrhoea.

PMID- 8880986
TI  - Fasciola hepatica infection in sheep: changes in liver metabolism.
AB  - Several aspects of liver function during infection with Fasciola hepatica were
      examined in sheep four weeks after infection and compared with the changes
      observed in infected rats. Previously reported respiratory abnormalities in
      mitochondria isolated from the left lobe of the liver of infected sheep were
      characterised further. Evidence is presented that the respiratory lesion is
      located in the mitochondrial electron transport chain and that the aberrant
      respiratory behaviour is not associated with an increase in nonesterified fatty
      acids and the depletion of mitochondrial phospholipids, as is the case in the
      rat. Microsomal membranes, which have also been shown to be depleted of
      phospholipids in the fluke-infected rat liver, showed no such changes in the
      sheep. However, in common with the rat, a substantial loss of cytochrome P450 was
      recorded in microsomes prepared from the left lobe, and the glycogen content of
      the left lobe was found to be less than 50 per cent of control values. No change
      was observed in glucose 6-phosphatase activity. All these changes were localised
      effects, confined to areas of fluke infiltration.

PMID- 8880987
TI  - Evaluation of thrombin-antithrombin complexes and fibrin fragment D in
      carbohydrate-induced acute laminitis.
AB  - Carbohydrate-induced laminitis has been associated with decreased platelet
      survival, decreased blood flow to the hoof wall and with the deposition of
      platelets and microthrombi within venules in the dermal laminae. To evaluate
      further the systemic prothrombotic events occurring in the prodromal stages of
      laminitis, plasma samples from control and laminitis-affected ponies and horses
      were tested for the presence of thrombin-antithrombin (TAT) complexes and fibrin
      fragment D (D-dimer). No statistically significant differences between the
      control and laminitis-affected animals were observed for either the D-dimer or
      the TAT complexes. Few of the values for individual animals exceeded the
      reference ranges for control animals. These data indicate that the prothrombotic
      events observed in carbohydrate-induced laminitis may not be associated with
      systemic activation of the coagulation or fibrinolytic systems.

PMID- 8880988
TI  - Measurement of bone specific alkaline phosphatase in the horse: a comparison of
      two techniques.
AB  - For many years total alkaline phosphatase (AP) activity in serum has been used to
      monitor bone metabolism in different species. However, total AP lacks bone
      specificity because the total activity in serum is made up of several isoenzymes,
      of which the liver and bone isoforms predominate. The aim of the present study
      was to evaluate an immunoradiometric assay for measuring bone specific alkaline
      phosphatase (BAP) in horses. BAP, a specific marker of bone formation, was
      measured in sera from thoroughbred horses by using a previously characterised
      wheat germ lectin (WGL) precipitation assay and an immunoradiometric assay. The
      levels of immunoreactive BAP (iBAP) and WGL precipitated BAP (wBAP) were related
      to the serum levels of total AP and another marker of bone formation, the carboxy
      terminal propeptide of type 1 collagen (PICP). In horses over one year old, iBAP
      correlated at least as strongly with total AP as with wBAP, which suggests that
      the immunoradiometric assay may partially cross-react with liver alkaline
      phosphatase in horse serum. This possibility was supported by the observation
      that there was a weaker correlation between iBAP and PICP than between wBAP and
      PICP. These data indicate that WGL precipitation is currently the most specific
      method for measuring bone specific alkaline phosphatase in horses.

PMID- 8880989
TI  - Acquired immunity in experimental feline Microsporum canis infection.
AB  - Seven adult cats were inoculated cutaneously at a shaved site with Microsporum
      canis; five (group A) had spontaneously recovered from a previous M canis
      infection, and two (group B) were dermatophyte-naive. Both of the dermatophyte
      naive cats developed typical clinical disease, the lesions reaching maximal size
      four to five weeks after exposure, and resolving by week 13. Only one of the
      group A cats developed clinical disease; the lesions were more inflammatory in
      nature and of shorter duration and had resolved by day 25 after exposure. Blood
      samples collected from the seven cats before and four weeks after exposure were
      assessed for M canis-specific cellular (by lymphocyte proliferation assays) and
      humoral (by IgG and IgM ELISA) immune responses. After four weeks the group A
      cats had significantly (P < 0.05) increased cellular and IgG-humoral immune
      responses, and the group B cats also had increased cellular, and IgG and IgM
      responses but the increases were not significant.

PMID- 8880990
TI  - Pharmacokinetics of propofol as an induction agent in geriatric dogs.
AB  - The pharmacokinetics of propofol were investigated in six unpremedicated dogs
      aged between eight-and-a-half and 10.5 years. After the induction of anaesthesia
      with a bolus dose of 5 mg kg-1 propofol administered intravenously, the trachea
      was intubated and anaesthesia was maintained with halothane in a gas mixture of
      oxygen and nitrous oxide. The mean (sd) t1/2 beta was 83.9 (14.8) minutes, the
      mean (SD) residence time was 99.0 (10.8) minutes, the mean body clearance was
      34.5 (12.1) ml kg-1 minute-1 and the mean volume of distribution at steady state
      was 3864 (1647) ml kg-1. The dose of propofol was lower than that recommended in
      the data sheet (6.5 mg kg-1) and was associated in some of these dogs over eight
      years of age with post-induction apnoea. The clearance of propofol was also
      slower than that previously reported in young dogs. These results have
      implications for infusion rates when propofol is used to maintain anaesthesia in
      dogs.

PMID- 8880991
TI  - Measurement of mechanical thresholds, plasma cortisol and catecholamines in
      control and lame cattle: a preliminary study.
AB  - The threshold response to a mechanical nociceptive stimulus was significantly
      lower on the lame hind limb of lame cows than on the same limb of sound cows.
      There were no significant differences between the concentrations of cortisol,
      noradrenaline, adrenaline or dopamine in the blood plasma of the sound and lame
      cows.

PMID- 8880992
TI  - Immunopathogenesis and physical maps of fowl adenovirus serotype 9.
AB  - Restriction endonuclease maps of the genome of fowl adenovirus (FAV) serotype 9
      have been constructed for the restriction endonucleases NdeI, NotI and XbaI. The
      total size of the FAV-9 genome was estimated to be 44.5 kb pairs, consistent with
      previous reports that FAV genomes are approximately 10 kb larger than human
      adenovirus (HAV). The pathogenicity of this virus in day-old chickens was
      intermediate between the pathogenicity of the non-pathogenic and the highly
      pathogenic FAVs.

PMID- 8880993
TI  - Effect of mixed infection of Mycoplasma gallinarum and Newcastle disease virus (F
      strain) on the tracheal epithelium of village chickens.
AB  - The effects of a mixed infection of Mycoplasma gallinarum and Newcastle disease
      virus (F strain) on the tracheal epithelium of village chickens were investigated
      and observed by scanning electron microscopy. Day-old village chicks were
      vaccinated intranasally with F strain Newcastle disease virus and inoculated
      intratracheally on the same day with 10(8) colony forming units of M gallinarum.
      In another study the chicks were vaccinated and then infected with M gallinarum
      seven days later. The first group of chicks was euthanased three, seven, 10, 14
      and 21 days after vaccination and infection and the vaccinated chicks were
      euthanased three, seven, 10 and 14 days after infection. In the chicks vaccinated
      and infected on the same day, major alterations to the tracheal epithelium were
      visible three days later. There were fewer ciliated cells and the borders of the
      non-ciliated cells were prominent. Several depressions had formed in the
      epithelial surface. At higher magnification, clumps of microvilli were visible on
      some of the non-ciliated cells. Seven days after vaccination and infection, the
      tracheal epithelium appeared normal, with an increase in the numbers of ciliated
      cells, although raised borders were observed on the non-ciliated cells in some
      areas. No clumping of microvilli or depressions in the epithelial surface were
      observed. In the chicks infected seven days after vaccination, the tracheal
      epithelium appeared normal with no visible changes on its surface.

PMID- 8880994
TI  - Characterisation of leucocytic somatic cells in bovine milk.
AB  - The mammary gland is of cutaneous origin with stromal leucocytic infiltrates and
      it excretes leucocytes in the milk. Milk T lymphocytes are highly enriched by
      sedimenting milk somatic cells in a 43 per cent preformed Percoll gradient.
      Thirty to 54 per cent of leucocytes, harvested from the upper Percoll band,
      belong to CD2+ CD3+ T lymphocytes. These milk T lymphocytes are mature CD4+, or
      CD8+ single positive T cells, expressing CD44, CD26, and beta 1 integrin, but not
      Lam-1. Milk T lymphocyte subsets may play an important role in regional
      immunosurveillance of the mammary epithelia and stroma. Selective mechanisms may
      account for the trafficking of this activated, memory T lymphocyte subset in the
      gland.

PMID- 8880995
TI  - Role of endogenous interferon in hepatitis C virus (HCV) infection and in
      coinfection by HIV and HCV.
AB  - Recombinant interferon alpha (IFN alpha), widely used in the treatment of chronic
      hepatitis C, can induce a major decrease in HCV viraemia in good responders. In
      order to evaluate the possible role of endogenous IFN, using a biological method,
      we measured the IFN levels in 74 patients infected by HCV and in 73 patients
      coinfected by HIV and HCV. IFN levels were much higher in the HCV+HIV+ group and
      were linked to HIV viraemia. In those patients with high IFN levels, the HCV
      viraemia was lower, but only in the HCV+ group. These data suggest that IFN can
      partly control the HCV viraemia, but in coinfection by HIV, the response of HCV
      to endogenous IFN could be lower.

PMID- 8880996
TI  - KSHV sequences in biopsies and cultured spindle cells of epidemic, iatrogenic and
      Mediterranean forms of Kaposi's sarcoma.
AB  - The pathogenesis of Kaposi's sarcoma (KS) is still unclear, and several factors
      appear to be involved in the onset of the Kaposi's lesion. Epidemiological
      studies suggest that a common infective agent may contribute to KS. Sequences
      which appear to represent a new gammaherpesvirus, currently termed KSHV/HHV8,
      have recently been identified in KS. To further examine the relationship between
      this virus and KS, we obtained biopsy samples of KS lesions; these samples, the
      spindle cells cultured from these lesions and the PBMC of the same patients were
      tested for the presence of KSHV sequences by PCR. In addition, we tested several
      "late passage" KS spindle cell lines as well as control samples. The biopsy
      samples were from lesions of the following forms of KS: one sporadic KS, two
      epidemic KS and three iatrogenic KS, one of which was in the process of
      regressing after reduction of immunosuppressive therapy, and two that were at
      different stages (patch and nodular) from a single patient. The sporadic KS
      specimen was positive, as were the PBMCs from this patient, and cells grown from
      this biopsy appeared to contain KSHV viral sequences up to the fifth passage.
      Both epidemic KS biopsies were positive, but in these cases KSHV sequences were
      not detected in the cultured cells. The biopsy from the regressing iatrogenic KS
      lesion was negative, as were the cells cultured from this lesion. However, the
      PBMCs of this patient were weakly positive for KSHV at the time of biopsy, and
      PBMCs collected from this patient one month later were completely negative. The
      samples of both the patch and the nodular KS lesions obtained from another
      immunosuppressed patient showed amplifiable sequences of KSHV, but both the PBMCs
      of this patient and primary KS cell cultures from these biopsies were negative.
      Of the late-passage KS lines tested, only one, IST AIDS KS 12, was positive for
      KSHV. This line is derived from an early angiomatous-macula lesion. Taken
      together, these data suggest that an active KSHV infection is associated with KS
      and that elimination of KSHV from the lesion precedes regression of the lesion,
      strongly correlating KSHV with KS. In addition, early KS lesions may have a
      higher KSHV burden, or contain cells more susceptible to KSHV infection, further
      linking KSHV to KS.

PMID- 8880997
TI  - Replication of circular and linear SV40-based plasmids in monkey cells.
AB  - Three plasmids were derived from a common SV40-based parent. A circular plasmid
      (pYACneoC) contained the SV40 ori and two sets of 50 bp of human telomeric
      sequences. By differential enzyme digestion, two linear plasmids were generated
      from the circular form, one (pYACneoL) terminating with, and the other (pYACneoN)
      free of telomeric sequences. The replicative features of the circular and of both
      linear plasmids were assayed by transfecting COS-7 cells. At various times after
      transfection, the low-molecular-weight DNA was extracted, and the fraction of
      molecules that had replicated was determined by Dpnl digestion. We demonstrate
      that about half of the circular plasmid molecules replicate, but only during a
      short time interval immediately following transfection. No replication was
      observed in the case of the two linear plasmids. However, the function of the
      SV40 origin is potentially present in the molecules, since circular forms that do
      replicate can be recovered from both linear plasmids. The extent of replication
      of circularized pYACneoL is similar to that of pYACneoC, whereas a lower fraction
      of circularized pYACneoN molecules replicate. These results are discussed in
      terms of the possible influence of the DNA structure on the viral ori, and of the
      influence of the host cell functions on viral replication.

PMID- 8880998
TI  - The antigen-specific cell-mediated immune response in mice is suppressed by
      infection with pathogenic lyssaviruses.
AB  - Responsiveness of T cells (RTC) was studied in BALB/c mice intramuscularly
      infected with various lyssaviruses. After infection by this peripheral route, two
      types of viruses could be classified according to their effects: 1) pathogenic
      viruses, including fixed rabies Pasteur virus (serogenotype 1) and wild viruses
      belonging to serogenotype 1 (from a rabid fox in France and from a cow infected
      by a vampire bat in Brazil) or to serogenotype 5 (European bat lyssavirus 1); and
      2) non-pathogenic viruses, including Mokola virus (serogenotype 3). RTC was
      tested by analysing in vitro the capacity of splenic T cells from infected BALB/c
      mice to produce cytokines after antigenic (purified lyssavirus antigens) or
      polyclonal stimulation (concanavalin A). Cytokine production was followed by
      assaying the biological activity of interleukin-2 and by testing for interleukin
      2, interleukin-4 and interferon-gamma (IL2, IL4 and IFN gamma ) messenger RNAs
      (mRNA) by transcription into complementary DNA and amplification by the
      polymerase chain reaction. The initial biologically active IL2 and cytokine mRNA
      production was observed in mice infected with pathogenic or non-pathogenic
      lyssaviruses. Only mice with symptoms (infected with pathogenic viruses) lost the
      capacity to produce cytokines in vitro after antigen-specific stimulation. No
      such loss was observed after polyclonal stimulation. In mice peripherally
      infected with non-pathogenic viruses, no loss was observed after stimulation with
      lyssavirus antigens. Thus, infection with pathogenic lyssaviruses by the
      peripheral route induces in BALB/c mice a loss of T-cell responsiveness after
      antigen activation, but not after polyclonal activation.

PMID- 8880999
TI  - Induction of rat CD4+ proliferative and mouse CD8+ cytotoxic T-cell lines
      specific for human papillomavirus type 16 antigens.
AB  - Infection by human papillomavirus type 16 (HPV16) has been associated with
      cervical dysplasia and carcinoma. To detect a possible cellular immune response
      against HPV16, we investigated the induction of T cells specific for antigens
      encoded by the virus. Two CD4+ T-cell lines with a specific proliferative
      response were isolated from the spleens of rats vaccinated using vaccinia virus
      vectors expressing E6 or E7 and challenged with syngeneic HPV-transformed cells.
      Two CD8+ T-cell lines with a specific cytotoxic activity were obtained from mice
      immunized using a syngeneic squamous cell tumour cell line transfected with the
      full-length HPV16 DNA. These results demonstrate that both CD8-mediated cytotoxic
      responses and CD4-mediated delayed-type hypersensitivity responses are involved
      in immunologic reactions to HPV antigens.

PMID- 8881000
TI  - In vitro determination of antiviral activity of MS8209, a new amphotericin B
      derivative, against primary isolates of HIV1.
AB  - MS8209, an amphotericin B derivative, was previously reported to be an inhibitor
      of HIV1 replication in vitro. In the present study, we determined the 50 and 90%
      in vitro inhibitory concentrations of MS8209 for 9 HIV1 isolates including both
      zidovudine-sensitive and zidovudine-resistant isolates and the reference strain
      Lai, using the peripheral blood mononuclear cell (PBMC) assay. We also evaluated
      the sensitivity of HIV1 replication to MS8209 during primary isolation from
      PBMCs. An inhibitory effect of MS8209 in PBMC infection was observed either when
      the drug was only present during the adsorption step or when the drug was
      initially absent but maintained throughout the culture period; the combination of
      these two approaches provided the highest inhibition rate. These results indicate
      that MS8209 can inhibit the replication of HIV1 isolates in PBMCs and suggest
      that it mainly acts by blocking the virus entry into cells.

PMID- 8881001
TI  - Easily applied ear canal electrodes improve the diagnostic potential of auditory
      brainstem response.
AB  - The diagnostic potential of easily applied ear canal electrodes was studied in
      patients with asymmetric auditory brainstem response (ABR). The study included 50
      consecutive patients with unilateral auditory signs or symptoms who at
      conventional ABR testing manifested not only a delayed wave V in relation to the
      non-symptomatic ear, but also absence of wave I in the symptomatic ear. The
      patients were examined with ear canal electrodes at the same session as the
      conventional ABR testing. As application of the ear canal electrode is easy,
      painless and safe, the auditory assistant could use the ear canal electrode and
      obtain the recordings unaided and without having first to consult a physician.
      Estimated extra time for the canal electrode procedure was 15 min and no adverse
      effects were noted. With the use of an ear canal electrode a significant wave I
      could be identified in 72% (36.50) of cases. Thus, ability to observe the most
      peripheral component (wave I) of the ABR was facilitated by using an easily
      applied ear canal electrode. Hence, in these patients the diagnostic potential of
      ABR for acoustic tumors was increased owing to the availability of a direct
      measure of tumor effect on the auditory nerve, i.e., the neural transmission
      time.

PMID- 8881002
TI  - Adaptive fitting of hearing instruments by category loudness scaling (ScalAdapt).
AB  - The introduction of programmable as well as non-linear hearing instruments has
      shown that audiogram-based fitting procedures are inappropriate for meeting the
      individual needs of hearing aid users with sensorineural loss. Particularly the
      present and future development of hearing instruments with advanced analog and
      digital signal processing requires suitable fitting procedures. In this context,
      we developed an adaptive fitting strategy (ScalAdapt) using category loudness
      scaling. In this paper the procedure is described and tested using programmable 3
      channel AGC instruments. However, it can be modified for any other hearing aid
      design. The underlying idea is to normalize the aided loudness perception for two
      input levels, one around the most comfortable level (MCL) and the other just
      below the uncomfortable level (UCL), as anchor points in each channel by
      interactive fine-tuning of the fitting parameters (channel gain, compression
      onset, compression ratio, etc.). The benefits of ScalAdapt have been evaluated by
      a field test study in 17 experienced hearing aid users. The results showed that
      ScalAdapt provides consistently higher objective (speech recognition in noise)
      and subjective benefits (self-assessment inventory) than for instance NAL-based
      fittings.

PMID- 8881003
TI  - Effects of the conditioning click on click-evoked otoacoustic emission.
AB  - The effects of the preceding (conditioning) click on the evoked otoacoustic
      emission (EOAE) to the following (test) click were investigated in normally
      hearing adults. To overcome distortions due to superimposition of the test EOAE
      on the EOAE to the conditioning click, a special stimulation and response
      subtraction procedure was utilized. The conditioning stimulus was found to
      suppress the test EOAE. The suppression lessened with a decrease in the
      conditioning stimulus level and an increase in the time interval between the
      conditioning and the test stimuli. Nevertheless, the influence was traced even
      with the level of the conditioning stimulus as low as 5 dB SL, and lasted for the
      interval between the conditioning and the test stimuli, as long as 7.5 ms. An
      attempt at theoretical comprehension of the obtained results is made and their
      usefulness in differentiation of EOAEs from acoustic reflections is proposed.

PMID- 8881004
TI  - Transient-evoked otoacoustic emissions and contralateral suppression in patients
      with unilateral tinnitus.
AB  - Transient-evoked otoacoustic emissions (TEOAE) have been recorded from 20
      patients with unilateral tinnitus and symmetrical hearing up to 2000Hz. Responses
      were digitally low-pass filtered at 2000Hz. The function of the medial
      olivocochlear system (MOC) was examined by contralateral acoustic stimulation
      (CAS) with broadband noise at 50 and 70 dB SPL. Emission amplitude was
      significantly lower in tinnitus ears in the 10-15ms part of the response. No
      difference in contralateral suppression of amplitude could be found. The latency
      shifts were small and were not helpful in separating tinnitus from non-tinnitus
      ears. Analysis on different parts of the response window may be a useful tool for
      separating tinnitus from non-tinnitus ears. The lack of efferent effect
      differences could result from influence of stimuli on tinnitus mechanisms.

PMID- 8881005
TI  - Transient-evoked otoacoustic emissions. Helpful tool in the detection of
      pseudohypacusis.
AB  - The object of the present study was to demonstrate the use of TEOAEs for
      diagnosing pseudohypacusis. Thirty-four patients were investigated for suspected
      pseudohypacusis based on the case history and clinical and audiological findings.
      TEOAEs confirmed the diagnosis in all cases except four patients with a pre
      existing organic hearing loss exceeding 25-30 dB HL. All the remaining 30
      patients showed normal TEOAE responses except four of the ears in which final
      assessment revealed hearing threshold lower than 30 dB in the middle frequency
      region. The method can be time-saving when performed at the first consultation.
      With its element of surprise, the patient can be confronted with the existence of
      a functional hearing loss. This frequently results in marked threshold
      improvement on repeat pure-tone audiometry.

PMID- 8881006
TI  - Temporary threshold shift induced by physical exercise.
AB  - Several studies have demonstrated how physical exercise can increase noise
      induced temporary threshold shifts (TTS), but until now no evidence of TTS
      exclusively attributable to physical activity has yet been reported. In this
      study the hearing pure-tone thresholds of 10 subjects were evaluated at rest and
      at three designated times following the end of a work load corresponding to 50%
      and 80% of the maximum oxygen uptake (VO2 max). The results obtained demonstrate
      a definite effect of physical exercise on the hearing threshold at 6000 and 8000
      Hz and that the higher the frequency, the greater the chance of detecting a TTS.
      Evaluation of the variations in some physiologic parameters (VO2 max, blood
      lactate and blood pressure) could not statistically correlate the same with TTS.
      The physiopathologic mechanisms responsible for TTS are still unknown and require
      further studies which should make allowances for the deferred effects of
      metabolic variations on the cochlear function.

PMID- 8881007
TI  - The influence of spontaneous otoacoustic emissions on the amplitude of transient
      evoked emissions.
AB  - The aim of the study was to analyse whether the presence of spontaneous
      otoacoustic emissions (SOAEs) in a group of normal-hearing adults is related to
      larger transient evoked otoacoustic emission (TEOAE) amplitudes when compared to
      a similar adult population without SOAEs. Twenty-four normal-hearing subjects
      participated in the investigation. They were selected to form two groups of 12,
      one containing only subjects with measurable spontaneous emissions, the other of
      members who had no measurable spontaneous emissions. Each group comprised 7 males
      and 5 females. TEOAEs were recorded in both linear and non-linear mode, and
      equivalent sound pressure levels in different octave frequency bands were
      calculated. For each frequency band, the comparison of the equivalent sound
      pressure levels in the two selected groups showed statistically significant
      differences. Therefore, when normative TEOAE data were collected with the purpose
      of establishing a normative reference for the assessment of cochlear hearing
      loss, it is mandatory to search for and, when pertinent, to compensate for the
      presence of SOAEs.

PMID- 8881008
TI  - Memory effects to be considered in the design of measurements of the influence of
      context on speech perception.
AB  - One of the experimental parameters needed for the design of testing procedures
      for measuring context utilization in speech perception is the magnitude of memory
      effects. Such memory effects were studied using data obtained from normal-hearing
      subjects in experiments during which test words were presented under noise either
      in isolation or in the context of sentences. Each test word was presented twice;
      during each presentation the subject heard the test word several (five or six)
      different times, under progressively higher signal-to-noise (S/N) ratios. When
      the second presentation of a test word occurred during the same 1 h session as
      the first presentation, the observed memory effect was very large, being
      equivalent to a shift in S/N ratio of the order of 5 dB. In experiments during
      which the second presentation of a test word occurred after an interval of
      several days following the first presentation, the observed memory effect was
      equivalent to a shift in S/N ratio of the order of 1 dB.

PMID- 8881009
TI  - Objective detection of auditory evoked potentials. Comparison of several
      statistical tests in the frequency domain by means of Monte Carlo simulations.
AB  - Fully objective assessment of the hearing threshold by auditory evoked potentials
      requires an objective detection of these responses by means of suitable
      statistical tests. The Rayleigh test, Watson's U2 test, Kuiper's test and Hodges
      Ajne's test check the phase angle distribution of a Fourier harmonics in a sample
      of stimulus-related EEG epochs. The modified Rayleigh test includes, in addition
      to the phase angles, the amplitude information in the form of ranks of the
      spectral amplitudes. To compare the signal detection performance of these tests,
      estimates of the probability density functions were calculated by means of
      extensive Monte Carlo simulations. From the probability density functions, the
      sensitivity of the tests was calculated and receiver operating characteristics
      (ROC) were constructed. The modified Rayleigh test appeared to be the most
      powerful test, followed by the Rayleigh test and Watson's U2 test. The
      application of Kuiper's test and Hodges-Ajne's test as well is not to be
      recommended for AEP detection.

PMID- 8881011
TI  - What's with epidemiologic meta-analyses?

PMID- 8881010
TI  - Topography of auditory evoked cortical potentials in children with severe
      language impairment.
AB  - Development of normal speech and language functions is closely related to normal
      hearing. However, most children with delayed or disturbed speech development show
      normal tone thresholds and here the investigation has to include higher levels in
      the auditory system. There is evidence for a connection between language
      impairment and a central auditory processing disorder, but the underlying
      mechanisms are not well understood. There is also a need for objective diagnostic
      methods of central auditory function. In the present study, a computerised method
      of mapping the scalp topography of long-latency (cortical) auditory evoked
      potentials (LAEP) was used for assessment of the function in central auditory
      pathways. Topographic mapping of the LAEP component N1, in adults and normal
      children, showed reproducible and valid results. In adults, a focal negativity,
      focus of NI (FNI), with a frontocentral position and contralateral to the
      stimulated ear was observed. The N1 maps in normal children showed a pattern
      similar to that in adults, but with some age-related changes. The N1 latencies
      declined significantly with age in normal children and reached adult values at
      the ages of 14-16 years. The topography of the LAEP components N1, P2, N2 and the
      T complex was investigated in 20 children with severe language impairment (LI).
      The study also included auditory brainstem responses (ABR),
      electroencephalography (EEG), quantitative EEG (qEEG) and magnetic resonance
      imaging (MRI). Twenty normal children served as controls (C). A similar
      topographic pattern was found in the LI and the C children, but with a higher
      proportion of deviating and non-focal maps in the LI group. The latencies of all
      components were significantly longer in the LI than in the C children. The
      diagnostic value of LAEP topography, latency and amplitude was estimated with a
      scoring system, whereby significantly higher scores were found in the LI group
      than in the C group. With all three parameters together the sensitivity was 65%,
      with a specificity of 90%. There was a high degree of pathological EEGs in the LI
      group. ABR abnormalities were seen in some LI subjects. MRI was normal in all but
      two LI children. There was no significant correlation between the results of EEG,
      ABR, MRI and the total score of LAEP, but some LI children showed a wide
      pathological pattern. In 17 of the 20 LI subjects a pathological result was
      obtained in one or more of the investigations. In conclusion, our results may
      indicate that language impairment has a dual pathophysiology, a specific auditory
      disorder (LAEP, ABR) and a non-specific general cerebral disturbance (EEG, MRI).
      The highly varying results among the present LI children, with specific and/or
      non-specific deviations, may be due to heterogeneity of the group with different
      aetiologies of their language impairment, or to a general developmental
      disturbance with a varying distribution and penetrance. The scoring system of
      LAEP proved to be the most sensitive method in separating the LI children from
      the controls. This may be a promising model for individual diagnostic criteria
      and for classification of language impairment.

PMID- 8881012
TI  - Sick building syndrome, work factors and occupational stress.
AB  - The sick building syndrome has been associated with certain buildings and
      environmental characteristics and is estimated to affect up to 30% of new or
      renovated buildings. Investigations have concentrated on physical factors, and it
      is only recently that psychological factors have been examined. Work and personal
      factors have also been considered. Occupational stress has been found to be
      correlated with symptoms of the sick building syndrome, but much of the research
      has been of a cross-sectional nature, and it does not indicate whether stress is
      an active element or an outcome. There is a clear need for further research in
      this area to examine stress, personality and physical factors associated with the
      sick building syndrome longitudinally. There is also a clear need to assess the
      validity of the historical and self-report methods used to assess the sick
      building syndrome.

PMID- 8881013
TI  - Validity of self-reported physical work load in epidemiologic studies on
      musculoskeletal disorders.
AB  - OBJECTIVES: This study assessed the validity of self-reported physical work load
      by questionnaire and logbook against task analysis and observation. It also
      investigated factors (job type and low-back or neck pain) affecting the self
      assessment of physical work load and compared the assessments between the
      questionnaire and the logbook. METHODS: A self-administered questionnaire
      including 10 questions (ordinal scales) on physical work load and musculoskeletal
      symptoms was filled out by 2756 men in the forest industry. From this population,
      36 men were selected for task analysis and observation. Logbooks including 10
      continuous variables were analyzed for 386 men. RESULTS: The Spearman rank
      correlation coefficients between the self-assessments and observations for the
      frequency of manual handling, duration of trunk flexion, neck rotation, hand
      above shoulder level, and squatting or kneeling ranged between 0.42 and 0.55. The
      correlation coefficients for the questionnaire items were higher in general, and
      the accuracy better, for those with no low-back pain than for those with pain.
      The duration of trunk flexion, neck flexion and hand above shoulder level was
      overestimated in the questionnaires and less so in the logbooks. CONCLUSIONS:
      Self-administered questionnaires may help to classify groups with heterogeneous
      occupational tasks according to some work-load factors. The accuracy of the
      assessments is not good for studying quantitative exposure-effect relationships,
      however. The logbook method might give more valid information. The perception of
      musculoskeletal pain may bias the self-assessment of work load.

PMID- 8881014
TI  - Dietary intake of fish contaminated with persistent organochlorine compounds in
      relation to low birthweight.
AB  - OBJECTIVES: The purpose of this study was to assess the hypothesized association
      between persistent organochlorine compounds through the consumption of fatty fish
      from the Baltic Sea (at the Swedish east coast) and low birthweight. MATERIALS
      AND METHODS: During the period 1973-1991, 72 cases of low birthweight (1500-2750
      g) were selected from among infants born to fishermen's wives within a cohort
      from the Swedish east coast. For each case two referents were selected. The
      mothers were interviewed about their dietary and smoking habits and place of
      living during childhood and adolescence. RESULTS: A high total current intake of
      fish from the Baltic Sea (> or = 4 meals per month) tended to increase the risk
      of having an infant with low birthweight [adjusted odds ratio (OR) 1.9, 95%
      confidence interval (95% CI) 0.9-3.9]. The effect was more conspicuous for the
      boys (OR 3.4, 95% CI 1.1-11). No such effects were observed when the estimated
      intake of fish was considered for the period in which the infant was born.
      However, mothers who had grown up in a fishing village had an increased risk of
      having an infant with low birthweight (OR 2.1, 95% CI 1.0-4.3). CONCLUSIONS: The
      variable "grown up in a fishing village" can be interpreted as an indirect
      measure of a mother's accumulated consumption of fish from the Baltic Sea. This
      idea supports an association between a high consumption of contaminated fish from
      the Baltic Sea and an increased risk for low birthweight. The effect estimates
      based on the mothers' reported fish consumptions were dependent on the period
      under consideration and therefore were somewhat ambiguous.

PMID- 8881015
TI  - Reproductive effects of paternal exposure to chlorophenate wood preservatives in
      the sawmill industry.
AB  - OBJECTIVES: The purpose of the study was to determine whether paternal
      occupational exposure to dioxincontaminated chlorophenols is associated with an
      increased risk of congenital anomalies or other adverse reproductive outcomes in
      offspring. METHODS: As a result of a multistep linkage, 19675 births between 1952
      and 1988 were identified as children of a cohort of 9512 fathers who had worked
      at least one year in British Columbia sawmills where chlorophenate wood
      preservatives had been used. A nested case-referent analysis was applied, using
      conditional logistic regression, with five referents matched per case according
      to year of birth and gender. Chlorophenate exposure was based on expert raters'
      estimations of hours of exposure applied to specific time windows prior to birth.
      RESULTS: The offspring of male sawmill workers were at increased risk for
      developing congenital anomalies of the eye, particularly congenital cataracts;
      elevated risks for developing anencephaly or spina bifida and congenital
      anomalies of genital organs were shown according to specific windows of exposure.
      No associations were found for low birthweight, prematurity, stillbirths, or
      neonatal deaths. CONCLUSIONS: The study adds further support to the hypothesis of
      male-mediated developmental toxicity. Paternal exposure to chlorophenates was
      associated with the development of certain congenital anomalies in offspring.

PMID- 8881016
TI  - Ubiquitous fiber exposure in selected sampling sites in Europe.
AB  - OBJECTIVES: This study evaluates personal exposure to respirable inorganic and
      organic fibers during normal human lifetimes and assesses the order of magnitude
      of the contribution of inorganic fibers other than asbestos to total fiber
      exposure from man-made and natural sources. METHODS: Four groups (suburban
      schoolchildren, rural retired persons, office workers, and taxi drivers), with
      five persons per group, were monitored for 24 h four times during one year.
      Personal sampling pumps collected airborne dust on gold-precoated Nuclepore
      filters. The fibers were analyzed for fiber sizes specified by the World Health
      Organization. RESULTS: The geometric mean concentrations ranged from 9000
      fibers.m-3 (office workers) to 20000 fibers.m-3 (schoolchildren) for organic
      fibers, and from 600 fibers.m-3 (taxi drivers) to 4000 fibers.m-3
      (schoolchildren) for gypsum fibers. For other inorganic fibers the concentrations
      were around 5000 fibers.m-3. The contribution of fibers with an elemental
      composition similar to that of man-made vitreous fibers (MMVF) was less than
      about one-quarter of the content of other inorganic fibers. The fiber size
      distributions were uniform across the groups, and the organic fibers were the
      longest and thinnest nonasbestos fibers. CONCLUSIONS: Lifetime exposure to fibers
      can be ranked as organic fibers > other inorganic fibers > fibers with an
      elemental composition similar to MMVF > MMVF. Information on the biological
      effects of fibers is difficult to interpret for use in assessing the health risk
      from exposure to low levels of ubiquitous fibers, and there is a lack of
      knowledge on the effects of organic fibers.

PMID- 8881017
TI  - Farming, pesticide use and hairy-cell leukemia.
AB  - OBJECTIVES: This paper analyzes the role of farming and pesticide exposures in
      the occurrence of hairy-cell leukemia (HCL). METHODS: The study included 226 men
      with HCL and 425 matched hospital referents. Pesticide exposure was assessed by
      expert review of detailed interview data on occupational histories and
      agricultural activities and exposures. RESULTS: Altogether, 77 cases and 116
      referents had farmed for at least six months, giving an odds ratio (OR) of 1.5
      [95% confidence interval (95% CI) 1.0-2.2]. Forage growing was reported by 20.8%
      of the cases and 11.1% of the referents and was associated with HCL (OR 2.8, 95%
      CI 1.6-4.9), even among farmers who had never handled pesticides (OR 3.4, 95% CI
      1.0-11.0). A significant association was found between HCL and pesticide use, the
      overall odds ratios for insecticide, fungicide, and herbicide use ranging from
      1.5 to 2.4. Organophosphorus insecticides were the only agrochemicals with a
      positive association with HCL after other pesticide exposures, smoking, and
      forage growing were accounted for. A clear-cut negative interaction was found
      between smoking and exposure to organophosphorus insecticides. A multivariate
      analysis yielded odds ratio estimates of 2.8 (95% CI 1.4-5.6) for exposure to
      forage and 7.5 (95% CI 0.9-61.5) for nonsmokers exposed to organophosphorus
      insecticides. CONCLUSIONS: The present study argues for a role of
      organophosphorus insecticides in HCL among nonsmoking farmers and shows an
      unexpected association with forage growing. No evidence of an association with
      phenoxyacetic acids, triazines, or organochlorine insecticides was found.

PMID- 8881018
TI  - Job strain and ambulatory blood pressure levels in a population-based employed
      sample of men from northern Italy.
AB  - OBJECTIVES: The purpose of this cross-sectional study was to examine the
      associations between categories of perceived job strain and blood pressure,
      measured by clinical and ambulatory devices on a population-based sample of
      employed men in northern Italy. METHODS: The study included 527 employed
      normotensive or mild hypertensive nonmedicated men enrolled in an age-gender
      stratified random sample of 821 25- to 64-year-old residents of the city of Monza
      (in the vicinity of Milan). The job-strain categories were classified according
      to the traditional quadrant-term approach and also a new approach based on the
      comparison of extreme tertile categories in order to enhance contrasts. Clinical
      blood pressure was measured according to the standardized MONICA procedure; 24-h,
      work, leisure, and nighttime blood pressure values were obtained with an
      ambulatory device. Disparities, calculated as differences between clinical and
      ambulatory measurements, were also analyzed. RESULTS: Among normotensive working
      men the highest mean for systolic blood pressure was found in the high-strain
      group, and progressively lower values were found in the passive, active and low
      strain categories. These patterns were observed for both the clinical and
      ambulatory measurements. Among the mild hypertensive subjects, lower mean values
      for ambulatory systolic and diastolic blood pressure were found in the passive
      and high job-strain categories when the tertile term approach was adopted. The
      passive group also showed the highest mean difference between the clinical and
      ambulatory measurements; this finding indicates that they may be more susceptible
      to alarm reactions. CONCLUSIONS: The results indicate that job strain affects
      blood pressure in population-based samples and the effect is consistent across
      sociocultural contexts.

PMID- 8881019
TI  - Regulations on occupational diseases and the current situation in Germany.

PMID- 8881020
TI  - Allergic alveolitis in a school environment.
AB  - BACKGROUND: A considerable fraction of newly constructed buildings have indoor
      air problems associated with health effects, usually of the nonspecific sick
      building syndrome variety. Specific health effects such as asthma, rhinitis, and
      allergic alveolitis can also occur. CASE: On 1 September 1988 a school teacher
      showed symptoms of an acute respiratory illness, which was first interpreted as
      pulmonary embolism and then later as atypical sarcoidosis. The illness slowly
      progressed over six years, at which time the diagnosis was revised to chronic
      allergic alveolitis, related to her school environment. The school had had indoor
      air quality problems off and on for several years. CONCLUSIONS: The case
      illustrates the difficulties of diagnosing cases of chronic allergic alveolitis,
      especially when it appears in environments where it is not generally encountered.
      It also raises questions regarding a possible relation between environments
      associated with the sick building syndrome and the occurrence of building
      associated illnesses.

PMID- 8881021
TI  - Significance testing of potential confounders and other properties of study
      groups--misuse of statistics.

PMID- 8881022
TI  - Molecular regulation of renal phosphate transport.

PMID- 8881023
TI  - Effects of mutating leucine to threonine in the M2 segment of alpha1 and beta1
      subunits of GABAA alpha1beta1 receptors.
AB  - The conserved leucine residues at the 9' positions in the M2 segments of alpha1
      (L264) and beta1 (L259) subunits of the human GABAA receptor were replaced with
      threonine. Normal or mutant alpha1 subunits were co-expressed with normal or
      mutant beta1 subunits in Sf9 cells using the baculovirus/Sf9 expression system.
      Cells in which one or both subunits were mutated had a higher "resting" chloride
      conductance than cells expressing wild-type alpha1beta1 receptors. This chloride
      conductance was blocked by 10 mM penicillin, a recognized blocker of GABAA
      channels, but not by bicuculline (100 microm) or picrotoxin (100 microm) which
      normally inhibit the chloride current activated by GABA: nor was it potentiated
      by pentobarbitone (100 microM). In cells expressing wild-type beta1 with mutated
      alpha1 subunits, an additional chloride current could be elicited by GABA but the
      rise time and decay were slower than for wild-type alpha1beta1 receptors. In
      cells expressing mutated beta1 subunits with wild-type or mutated alpha1 subunits
      (alphabeta(L9'T) and alpha(L9'T)beta(L9'T)), no response to GABA could be
      elicited: this was not due to an absence of GABAA receptors in the plasmalemma
      because the cells bound [3H]-muscimol. It was concluded that in GABAA channels
      containing the L9'T mutation in the beta1 subunit, GABA-binding does not cause
      opening of channels, and that the L9'T mutation in either or both subunits gives
      an open-channel state of the GABAA receptor in the absence of ligand.

PMID- 8881024
TI  - Heterogeneity of volume-sensitive chloride channels in basolateral membranes of
      A6 epithelial cells in culture.
AB  - A new technique allowing single-channel patch-clamp recordings from basolateral
      membranes of A6 renal epithelial cells in culture was developed. Using this
      technique we studied the chloride channels activated in these basolateral
      membranes during hypo-osmotic stress. Four different types of channel were
      identified and classified according to their current/voltage (I/V) relationships
      as observed in the on-cell configuration of the patch-clamp technique. Three of
      these channels had linear I/V relationships with unitary conductances of 12, 30
      and 42 pS. The fourth type had an outwardly rectifying I/V curve with inward and
      outward conductances of 16 and 57 pS respectively. The kinetic properties of each
      class of channel were studied and kinetic models developed for two of them: the
      42 pS channel and the outward rectifier. These models permitted the study of the
      evolution of the kinetic parameters during hypo-osmotic shock and revealed two
      different kinetic schemes of channel activation. The results of experiments made
      on the basolateral membranes were also compared with those of a set of analogous
      patch-clamp experiments carried out on isolated A6 cells. In these latter, the
      frequency of successful observations of active channels in a patch was 13%,
      whereas it was 31% for basolateral membranes. Also, of the four types of channel
      observed in basolateral membranes, two were never found in isolated cells, only
      the 12 pS channel and the outward rectifier were present in these isolated cells.

PMID- 8881025
TI  - ADH action on whole-cell currents by cytosolic Ca2+-dependent pathways in
      aldosterone-treated A6 cells.
AB  - We studied the characteristics of the basal and antidiuretic hormone (arginine
      vasotocin, AVT)-activated whole cell currents of an aldosterone-treated distal
      nephron cell line (A6) at two different cytosolic Ca2+ concentrations ([Ca2+]c, 2
      and 30 nm). A6 cells were cultured on a permeable support filter for 10
      approximately 14 days in media with supplemental aldosterone (1 microM). At 30 nm
      [Ca2+]c, basal conductances mainly consisted of Cl- conductances, which were
      sensitive to 5-nitro-2-(3-phenyl-propylamino)-benzoate. Reduction of [Ca2+]c to 2
      nm abolished the basal Cl- conductance. AVT evoked Cl- conductances at 2 as well
      as 30 nm [Ca2+]c. In addition to Cl- conductances, AVT induced benzamil
      insensitive nonselective cation (NSC) conductances. This action on NSC
      conductances was observed at 30 nm [Ca2+]c but not at 2 nm [Ca2+]c. Thus,
      cytosolic Ca2+ regulates NSC and Cl- conductances in a distal nephron cell line
      (A6) in response to AVT. Keeping [Ca2+]c at an adequate level seems likely to be
      an important requirement for AVT regulation of ion conductances in aldosterone
      treated A6 cells.

PMID- 8881026
TI  - Identification of ATP-sensitive potassium channel in frog ventricular myocytes.
AB  - ATP-sensitive potassium channels were found in frog ventricular myocytes using
      the inside-out patch-clamp technique. The channel was selectively permeable to
      K+. Single-channel conductance was 32.6 pS at 3.0 mM of [K+]o and 132 mM [K+]i
      and 77.3 pS at 114 mM [K+]o and 132 mM [K+]i. ATP did not affect single-channel
      conductance. The open probability of the channel was decreased by intracellular
      application of ATP in both the presence and absence of 2 mM MgCl2. The
      coexistence of Mg2+ with ATP shifts the dose-response curve for the open
      probability of ATP-sensitive K+ channel against ATP rightward. The shift of the
      curve indicates that Mg-ATP is less effective than free ATP in inhibiting the
      channel. An open-time histogram was fitted by a single exponential function with
      a time constant of 1.63 +/- 0.17 msec (n = 5) in an ATP-free medium. Mean open
      time (1.57 +/- 0.10 msec; n = 5) was not altered but the inter-burst time (closed
      time between bursts) lengthened in 10 microM ATP.

PMID- 8881027
TI  - A mathematical model of the pancreatic ductal epithelium.
AB  - A mathematical model of the HCO-3-secreting pancreatic ductal epithelium was
      developed using network thermodynamics. With a minimal set of assumptions, the
      model accurately reproduced the experimentally measured membrane potentials,
      voltage divider ratio, transepithelial resistance and short-circuit current of
      nonstimulated ducts that were microperfused and bathed with a CO2/HCO-3-free,
      HEPES-buffered solution, and also the intracellular pH of duct cells bathed in a
      CO2/HCO-3-buffered solution. The model also accurately simulated: (i) the effect
      of step changes in basolateral K+ concentration, and the effect of K+ channel
      blockers on basolateral membrane potential; (ii) the intracellular acidification
      caused by a Na+-free extracellular solution and the effect of amiloride on this
      acidification; and (iii) the intracellular alkalinization caused by a Cl--free
      extracellular solution and the effect of DIDS on this alkalinization. In
      addition, the model predicted that the luminal Cl- conductance plays a key role
      in controlling both the HCO-3 secretory rate and intracellular pH during HCO-3
      secretion. We believe that the model will be helpful in the analysis of
      experimental data and improve our understanding of HCO-3-transporting mechanisms
      in pancreatic duct cells.

PMID- 8881028
TI  - Ionic channels of the sugar beet tonoplast are regulated by a multi-ion single
      file permeation mechanism.
AB  - Ionic channels of the sugar beet tonoplast were studied using the patch-clamp
      technique. At micromolar concentrations of cytosolic calcium, several (at least
      four) distinct single-channel current levels were routinely identified. On the
      basis of channel voltage dependence, kinetic properties and conductance of single
      openings, the largest channel (103 +/- 2 pS in symmetric 150 mm KCl) corresponds
      to the slow vacuolar (SV) channel already identified by Hedrich and Neher (1987).
      The majority of the whole-vacuole current was ascribed to this time-dependent
      slow-activating channel elicited by positive vacuolar potentials. The channel of
      intermediate amplitude (41 +/- 1 pS in 150 mM KCl) did not show any voltage
      dependence and delay in the activation upon the application of voltage steps to
      both positive and negative transmembrane potentials. Owing to its voltage
      independence this channel was denominated FV1. The opening probability of the SV
      type channel increased by increasing the cytoplasmic calcium concentration, while
      the activity of the FV1 channel did not increase appreciably by changing the
      calcium concentration in the range from 6 microM to 1 mM. All the channels
      identified showed a linear current-voltage characteristic in the range +/-100 mV
      and at least the three most conductive ones displayed potassium selectivity
      properties. Substitution of potassium with tetramethylammonium (TMA) on the
      cytosolic side demonstrated that both the SV and FV1 channels are impermeable to
      TMA influx into the vacuole and support the potassium selectivity properties of
      these two channels. Moreover, the single channel conductances of all the channels
      identified increased as a function of the potassium concentration and reached a
      maximum conductivity at [K+] approximately 0.5 M. This behavior can be explained
      by a multi-ion occupancy single-file permeation mechanism.

PMID- 8881029
TI  - Chloride-induced Ca2+ release from the sarcoplasmic reticulum of chemically
      skinned rabbit psoas fibers and isolated vesicles of terminal cisternae.
AB  - There is increasing evidence that Ca2+ release from sarcoplasmic reticulum (SR)
      of mammalian skeletal muscle is regulated or modified by several factors
      including ionic composition of the myoplasm. We have studied the effect of Cl- on
      the release of Ca2+ from the SR of rabbit skeletal muscle in both skinned psoas
      fibers and in isolated terminal cisternae vesicles. Ca2+ release from the SR in
      skinned fibers was inferred from increases in isometric tension and the amount of
      release was assessed by integrating the area under each tension transient. Ca2+
      release from isolated SR was measured by rapid filtration of vesicles passively
      loaded with 45Ca2+. Ca2+ release from SR was stimulated in both preparations by
      exposure to a solution containing 191 mm choline-Cl, following pre-equilibration
      in Ca2+-loading solution that had propionate as the major anion. Controls using
      saponin (50 microg/ml), indicated that the release of Ca2+ was due to direct
      action of Cl- on the SR rather than via depolarization of T-tubules. Procaine (10
      mM) totally blocked Cl-- and caffeine-elicited tension transients recorded using
      loading and release solutions having ([Na+] + [K+]) x [Cl-] product of 6487.69
      mm2 and 12361.52 mm2, respectively, and blocked 60% of Ca2+ release in isolated
      SR vesicles. Surprisingly, procaine had only a minor effect on tension transients
      elicited by Cl- and caffeine together. The data from both preparations suggests
      that Cl- induces a relatively small amount of Ca2+ release from the SR by
      activating receptors other than RYR-1. In addition, Cl- may increase the Ca2+
      sensitivity of RYR-1, which would then allow the small initial release of Ca2+ to
      facilitate further release of Ca2+ from the SR by Ca2+-induced Ca2+ release.

PMID- 8881030
TI  - Cloning and chromosomal mapping of the mouse DNA-dependent protein kinase gene.
AB  - Severe combined immune deficiency (scid) mice are assumed to have two types of
      abnormalities: one is high radiosensitivity and the other is abnormal
      recombination in immunoglobulin and T-cell receptor genes. The human chromosome 8
      q1.1 region has an ability to complement the scid aberrations. Moreover, the
      localization of the subunit DNA-dependent protein kinase [DNA-PKcs] participating
      in DNA double-strand break repair in the same locus was clarified. In scid mouse
      cells, the number of DNA-PKcs products and extent of DNA-PK activity remarkably
      decrease. These observations gave rise to the assumption that DNA-PKcs is the
      scid factor itself. In order to determine whether the DNA-PKcs gene is the scid
      gene, we isolated the mouse DNA-PKcs gene and investigated its chromosomal locus
      by fluorescence in situ hybridization (FISH). Consequently, it became clear that
      the mouse DNA-PKcs gene existed in the centromeric region of mouse chromosome 16,
      determined by cross-genetic study, as a scid locus. This finding strongly
      suggests that mouse DNA-PKcs is the scid gene.

PMID- 8881031
TI  - MHCDB: database of the human MHC (release 2).
AB  - The second release of the human major histocompatibility complex (MHC) database
      is now publicly available. It contains an updated physical map and considerably
      more genomic sequence. cDNA sequences of all current alleles are accessible as
      individual sequence entries. The variability of different genes is displayed
      graphically as static and dynamic images accessible from the database. Known
      disease-serotype associations have also been incorporated, together with data
      from the MHCPEP database of eluted peptides.

PMID- 8881033
TI  - A roadmap for HLA-A, HLA-B, and HLA-C peptide binding specificities.
AB  - The high level of polymorphism in major histocompatibility complex (MHC)
      molecules leads to many allele-specific peptide binding repertoires that can
      generally be characterized by sequence motifs. Such motifs have previously been
      elucidated experimentally for several MHC molecules and shown to bind in
      specificity pockets in the antigen binding cleft. Here, a new and less
      restrictive description of the traditional antigen binding pockets is derived.
      These regions are referred to as peptide binding environments and are defined as
      those residues in a fixed neighborhood of the peptide residues in known crystal
      structure complexes. By examining the antigen binding environments from MHC
      molecules with known motifs, we made predictions as to likely motifs for other
      MHC molecules which share the same environments. The predictions are presented in
      the form of Tables and are pertinent to class I HLA-A, HLA-B, and HLA-C MHC
      sequences, and are shown to correlate well with experiments.

PMID- 8881032
TI  - Cloning of T-cell antigen receptor beta chain cDNAs from Atlantic salmon (Salmo
      salar).
AB  - Atlantic salmon (Salmo salar) cDNAs encoding the T-cell antigen receptor beta
      chain (TCRB) were isolated from leukocyte RNA by reverse transcription -
      polymerase chain reaction (RT-PCR). Twenty-five distinct cDNA fragments covering
      the variable (V) - diversity (D) - joining (J) junction and part of the constant
      (C) region were characterized; the sequences of which indicate interchangeable
      V/D/J usage and expression in the context of one TCRBC gene. Full-length TCRBC
      sequence information was derived from a leukocyte cDNA library. Key residues of
      the salmon TCRBC region are in good agreement with those of other species. One
      distinct exception is the absence of the hinge region cysteine residue which is
      involved in covalent bonding between the alpha and beta chain in mammalian TCRs.
      As in amphibian and avian species, the salmon TCRBC membrane proximal region is
      considerably shorter than the mammalian. An octamer sequence (GGACAGGG) very
      similar to amphibian, avian, and mammalian D sequences could be recognized in the
      VDJ junctions from salmon. The pattern of VDJ variability also indicates that
      mechanisms like trimming and addition occur in fish as in higher vertebrates.
      Compared with mammals, a relatively high frequency (32%) of the VDJ junctions in
      salmon were out of frame.

PMID- 8881034
TI  - Recognition by human Vgamma9/Vdelta2 T cells of melanoma cells upon fusion with
      Daudi cells.
AB  - Daudi Burkitt's lymphoma cells, unlike other tumor cell lines, stimulate human T
      cells coexpressing the variable (V) region genes TCRG-V9 and V TCRD-V2 to
      proliferate and secrete lymphokines. Hybrids, derived by the fusion of Daudi
      cells with the human melanoma cell line MZ2-MEL 2.2, retain the morphology of
      melanoma cells. Unlike the parental melanoma cell line, these Daudi x MZ2-MEL 2.2
      hybrids stimulate secretion of tumor necrosis factor (TNF) and
      granulocyte/macrophage colony stimulating factor (GM-CSF) by CD4-positive
      Vgamma9/Vdelta2 T-cell clones. Whereas the stimulator phenotype of Daudi cells
      behaves as a dominant trait in Daudi x melanoma hybrids, the expression of B-cell
      differentiation markers is suppressed. Thus, the gamma/delta T-cell ligand
      expressed by Daudi cells behaves as a dominant tumor antigen in Daudi x melanoma
      hybrids and is unrelated to the differentiated B-cell phenotype. Dominant
      expression of the Daudi ligand for human Vgamma9/Vdelta2 T cells in these hybrids
      may provide a basis for defining the stimulatory principle at the molecular
      level.

PMID- 8881035
TI  - Genomic organization and chromosomal localization of the mouse Bp3 gene, a member
      of the CD38/ADP-ribosyl cyclase family.
AB  - The mouse Bp3 antigen is a variably glycosylated phosphatidylinositol-linked cell
      surface glycoprotein expressed on early B and T lineage cells, myeloid cells,
      intestinal epithelial cells, and a discrete population of reticular cells in
      peripheral lymphoid tissues. The deduced amino acid sequence of Bp3 cDNA shares
      significant similarity to human and mouse CD38 and molluscan ADP-ribosyl cyclase,
      enzymes that generate the calcium mobilizing agent cyclic ADP-ribose from NAD. In
      this study, we cloned and characterized the Bp3 gene. The gene consists of nine
      exons and spans approximately 27 kilobases. The overall exon organization is very
      similar to that reported for the ADP-ribosyl cyclase gene in the mollusc Aplysia
      kurodai. The Bp3 gene is located on mouse chromosome 5 very near the gene for
      CD38, suggesting that this family arose by gene duplication. The major
      transcriptional start site of the Bp3 gene in a pro-B cell line (-17 from the ATG
      start codon) contains a weak initiator sequence. The upstream region lacks a TATA
      box, but contains consensus recognition sequences for the PU. 1, Ikaros/LyF-1,
      E2A, and TCF-1 transcriptional factors that regulate gene expression in lymphoid
      and myeloid cells. Consensus motifs for cytokine responsive factors NF-IL6/C-EBP,
      H-APF-1/APRF, and AP-1 are also present in the flanking region, and interleukin-6
      treatment enhances expression of the Bp3 antigen by a myeloblastoid cell line.

PMID- 8881036
TI  - A second immunoglobulin light chain isotype in the rainbow trout.
AB  - A novel immunoglobulin (Ig) light chain isotype, termed IgL2, has been isolated
      from trout lymphoid tissues both by reverse transcription - polymerase chain
      reaction (PCR) and screening of cDNA libraries. The CL domain of the new isotype
      shares only 29% residues with a recently cloned trout IgL isotype, termed IgL1,
      which has some similarities to Ckappa and Clambda isotype domains of several
      vertebrate species. Using anchored PCR, a VL element rearranged to CL2 was
      isolated. It is a member of a new VL family (VL2) of which four members were
      sequenced. These differ in the sequence of CDR1 and CDR2 but are remarkably
      similar in CDR3, i. e., at the junction between VL and JL segments. VL elements
      are rearranged to novel JL elements which differ from those described for VL1-CL1
      rearrangements. Two cDNA clones contained JL-CL2 segments but no VL segments. The
      JL segments were preceded by typical rearrangements signal sequences [RSS,
      nonamer-23 base pair (bp) spacer-heptamer]. Further upstream of RSS were located
      two to three near identical 53 bp repeats, each of which included a 16 bp
      sequence similar to KI and KII sequences located at similar places in human and
      mouse Jk1 genes. These sequences are believed to act as binding sites for the
      protein KLP, which could be a transcriptional factor involved in the synthesis of
      germline Jk transcripts. Their phylogenic conservation in vertebrates suggests
      that they have an important role in B-cell differentiation. Remarkably, an RNA
      species of about 0.7 kilobase is the predominant IgL mRNA in trout spleen and
      coincides in size with JLCL2 transcripts. Genomic DNA blot analysis indicates
      that the trout L2 locus has a cluster-like organization similar to the trout L1
      locus and the IgL locus of several teleost fish. A phylogenic analysis of VL2 and
      CL2 corroborates their low similarity to other vertebrate IgL chains and suggests
      an ancient diversification of the IgL locus.

PMID- 8881037
TI  - Histocompatibility antigen(s) linked to Rfp-Y (Mhc-like) genes in the chicken.
AB  - Major histocompatibility complex (Mhc) genes influencing transplantation
      rejections were first described in mice within the H2 complex and secondly in
      chickens within the B complex. In chickens, Rfp-Y haplotypes have recently been
      identified which contain class I and class II Mhc-like genes that assort
      independently of the B complex. Three Rfp-Y haplotypes have been defined in a
      closed breeding flock of line N chickens. In this study, progeny were obtained
      from line N Rfp-Y heterozygous matings to establish the role of Rfp-Y in
      transplantation immunity. Rfp-Y incompatibility did not induce significant one
      way mixed lymphocyte responses. However, Rfp-Y-incompatible skin grafts were
      rejected more frequently and at a faster rate than Rfp-Y-compatible grafts by two
      week-old chicks. The control Mhc B-incompatible grafts were rejected faster than
      the Rfp-Y-incompatible grafts; the latter were rejected at speeds that resemble
      rejection of minor histocompatibility antigens. We conclude that Rfp-Y class I
      and II Mhc-like genes are linked to the expression of minor histocompatibility
      antigens in chickens.

PMID- 8881038
TI  - Enhancers of hypermutation.
AB  - Hypermutation at the immunoglobulin (Ig) loci increases the mutation rate more
      than 10(5)-fold over the normal, spontaneous rate. We studied two kinds of cis
      acting elements - 3' enhancers and promoters - in a system in which a gene
      encoding the mu heavy (H) chain (Igm) is transfected in vitro into a cell line
      with an active Ig mutator. A construct containing a rearranged Igm gene requires
      the 3' H enhancer for hypermutation at a rate comparable with the one at the
      endogenous gene segment encoding the H chain variable region (V). Without the 3'
      enhancer, the basal mutational activity is much lower, but still higher than the
      normal, spontaneous mutation rate. Replacement of the 3' H enhancer by atopic
      elements of similar function also supports full hypermutation. Even though these
      3' elements are defined as transcriptional enhancers, they do not seem to
      increase hypermutation via an increase in the rate of transcription. Replacement
      of the endogenous promoter by the tk promoter slightly increases hypermutability
      of the construct; thus, no specific sequences in the Ig promoter are likely to
      target hypermutation.

PMID- 8881039
TI  - CTL respond to a mitochondrial antigen presented by H2-Db.

PMID- 8881040
TI  - A tunicate (Botryllus schlosseri) cDNA reveals similarity to vertebrate antigen
      receptors.

PMID- 8881041
TI  - Nucleotide sequences of three distinct cDNA clones coding for the rat class I
      heavy chain RT1n antigen.

PMID- 8881042
TI  - Sequencing of a new HLA-A*32 subtype (A*3202).

PMID- 8881043
TI  - Molecular characterization of HLA-A*6803.

PMID- 8881044
TI  - A new sequence (Mhc-BJ ) showing similarity both to Mhc-B alleles and to the HLA
      J pseudogene in Macaca mulatta.

PMID- 8881045
TI  - A second polymorphic dinucleotide repeat in the 5' flanking region of the human
      IL10 gene.

PMID- 8881046
TI  - Identification of a new HLA-A allele (A*2502) by PCR-SSP.

PMID- 8881047
TI  - Laparoscopy in colorectal surgery.

PMID- 8881048
TI  - Laparoscopic assisted colectomy.
AB  - BACKGROUND: The role and feasibility of laparoscopic assisted colectomy (LAC) in
      both benign and malignant disease of the colon are not clear. We have reviewed
      our series in an effort to further delineate whether or not LAC is appropriate in
      the treatment of colonic disease. METHODS: This is a retrospective view of a
      personal series focusing on feasibility, cure of malignant disease, and length of
      stay (LOS). RESULTS: One hundred and two LACs were completed out of 104 attempts
      (98%). There were no wound or trocar implants in the Dukes A, B and C patients.
      Lymph node retrieval was similar in the laparoscopic and open historical
      controls. The LOS was 5.9 days in the LAC group as compared with 11 days in the
      open group. There was a 4.8% major morbidity rate and a 1% mortality rate in this
      series. CONCLUSIONS: LAC is technically feasible in a high percentage of
      patients. While a definite statement regarding its use in malignant disease can
      not be ascertained from this review, the preliminary results are encouraging. A
      randomized trial comparing open and LAC is warranted.

PMID- 8881049
TI  - Laparoscopic management of acute cholecystitis. Prognostic factors for success.
AB  - BACKGROUND: Laparoscopic cholecystectomy for acute cholecystitis is considered
      feasible and safe, but it is associated with a higher rate of conversion to
      laparotomy than elective cholecystectomy because of technical reasons and
      anatomical changes related to the inflammatory process. The value of several
      factors that might influence its successful completion has not been studied
      completely yet, including the role of residents in operating such cases under
      attending-surgeon surveillance. METHODS: In a retrospective nonrandomized study,
      the medical charts of 182 patients that were operated for acute cholecystitis (94
      of whom via the laparoscopic approach) were studied. The study was also conducted
      to study the effect of residents as operators. RESULTS: Male sex, duration of
      right upper abdominal pain, and the severity of the inflammatory process have all
      been significantly and independently correlated with increased conversion rate to
      laparotomy. Operation time was not longer than that of the open approach, and
      hospital stay and complication rate were lower. Operations performed by residents
      were associated with twofold conversion rate to laparotomy, without increased
      complication rate (p < 0.012). CONCLUSIONS: Laparoscopic management of acute
      cholecystitis is feasible and safe. Considering the factors discussed above,
      lowering the threshold for conversion is necessary in selected cases to maintain
      low morbidity rate. Integrating laparoscopic cholecystectomy for acute
      cholecystitis into surgical residency should be studied.

PMID- 8881050
TI  - Laparoscopic colon and rectal surgery at a VA hospital. Analysis of the first 50
      cases.
AB  - BACKGROUND: Laparoscopic techniques were utilized for all colon and rectal
      procedures undertaken by a single surgeon at the West Haven VA Hospital beginning
      in August of 1991. METHODS: All patients were entered into a registry, and data
      was gathered prospectively. This report comprises the first 50 patients. These
      patients were compared with 34 consecutive patients undergoing open operations
      during the same time period. RESULTS: Overall, 33 patients (66%) were completed
      laparoscopically. This increased to 87% after the first 20 patients. Patients
      undergoing laparoscopic procedures showed significant improvement over the open
      and converted patients in several areas. Operative blood loss was decreased. They
      ate sooner (3.7 days) and required less postoperative pain medication. Major
      complications were less common after laparoscopic operations. Average length of
      stay was 8.3 days, compared with 13.9 days and 14.5 days in the converted and
      open groups, respectively. There was no difference in the operative time between
      laparoscopic and open cases; time for converted cases was significantly longer.
      There was no difference in lymph node counts among the three groups in patients
      with resections for cancer. CONCLUSIONS: Laparoscopic colorectal surgery is safe
      and effective, although its efficacy in malignant disease is uncertain. Patients
      enjoy the same benefits derived from other laparoscopic procedures. Although
      there appears to be a longer learning curve associated with the procedure,
      minimally invasive techniques should become utilized more frequently for patients
      with colorectal disease.

PMID- 8881051
TI  - Thoracoscopic pleurodesis with minocycline vs talc in the porcine model.
AB  - BACKGROUND: Eighteen adult pigs (Sus scrofa) underwent thoracoscopy and were
      placed into one of three groups: no sclerosant, talc pleurodesis, or minocycline
      pleurodesis. METHODS: Animals were then sacrificed at matched time intervals.
      Gross inspection of the pleural cavity estimated percentage of pleural symphysis
      (>25% was considered substantial) and allowed assignment of a pleurodesis score
      based on a scale described by Bresticker. Microscopic examination evaluated
      degree of fibrosis as mild, moderate, or severe. RESULTS: The talc group had
      significantly better pleurodesis than the minocycline group as determined by (1)
      the proportion of animals with substantial surface pleural symphysis (5/6 vs 1/6,
      p < 0.01), (2) a higher pleurodesis score (3 vs 1.3, p < 0.05), and (3) the
      proportion of animals with moderate fibrosis (5/6 vs 0/6, p < 0. 01).
      CONCLUSIONS: The authors conclude that instillation of aerosolized talc produces
      significantly better fibrosis and pleural symphysis than atomized minocycline in
      this animal model.

PMID- 8881052
TI  - Comparison between laparoscopic and conventional omental patch repair for
      perforated duodenal ulcer.
AB  - BACKGROUND: The aim of the study is to evaluate the safety and efficacy of
      laparoscopic omental patch repair. METHOD: This is a retrospective review of 53
      consecutive patients with omental patch repair for perforated duodenal ulcer; 38
      underwent conventional open approach and 15 underwent laparoscopic patch repair.
      The only selection criterion was availability of expertise for laparoscopic
      repair on the day of admission. By chance, the open group had poorer ASA scores.
      There were four deaths and five postoperative complications in the open group.
      RESULTS: Laparoscopic repair was successful in 14 cases with one postoperative
      complication. Operative time was longer in the laparoscopic group (80 vs 65 min
      in open group, p = 0.02). Patients required less postoperative analgesics in the
      laparoscopic group (median amount of pethidine was 75 mg vs 175 mg in the open
      group, p = 0.03). There was no statistically significant difference in terms of
      hospital stay and return to normal activities between the two procedures. Follow
      up Visick scores were comparable in both groups. CONCLUSIONS: Laparoscopic
      omental patch repair offers a safe alternative to the conventional method and
      causes less postoperative pain.

PMID- 8881053
TI  - Laparoscopic choledochotomy with primary closure. Follow-up (5-44 months) of 31
      patients.
AB  - BACKGROUND: Thirty-three patients were candidates for laparoscopic
      choledochotomy. The indications for this operation are described. METHODS: The
      procedure was completed 32 times (97%). We had 29 successful common bile duct
      (CBD) clearances, three negative explorations, and one failed clearance which
      needed to be converted to laparotomy. All the completed procedures ended with
      primary closure of the main duct. Median duration of surgery was 180 min (range
      100-300), including three associated laparoscopic procedures. RESULTS: There were
      three postoperative complications (9.4%), none major. Average postoperative
      hospital stay was 7.1 days (range 4-14). In May-June 1995 we controlled 31 out of
      the 32 consecutive patients (one patient was lost to follow-up) who had a
      successful laparoscopic choledochotomy from October 1991 to December 1994. Median
      follow-up was 22 months (range 5-44). Besides clinical control, 23 patients also
      had ultrasound (US) controls and 24 had blood tests. Eleven had intravenous
      cholangiotomography. Two patients died 11 and 22 months after the operation for
      unrelated causes and without biliary symptoms. Two patients had umbilical
      hernias. One had a small residual asymptomatic stone, which was removed
      endoscopically. None had signs of postoperative CBD stricture. At US, CBD was
      </=7 mm in 15 patients, 8-10 mm in four patients, and 10-12 mm in three patients.
      The last group had preoperative CBD dilation, too. We could compare preoperative
      and postoperative CBD diameters in 22 patients: 11 had no change; in nine it
      decreased; and two had a slight increase (8-10 mm). CONCLUSIONS: We conclude that
      laparoscopic choledochotomy with primary closure is a very good operation: It has
      a high success rate and low morbidity. Mortality is nil so far. Medium-term
      results are very positive: We had no CBD stricture and only one case of
      asymptomatic residual stone, which could have been avoided. Our results suggest
      that intraductal biliary drainage is useless, and its specific complications are
      well known.

PMID- 8881054
TI  - Activation of coagulation and fibrinolysis in open and laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Activation of coagulation and fibrinolysis occurs as a stress
      response to surgery and may predispose the patient to thromboembolic
      complications. Other components of the surgical stress response (cytokine
      release, neurohumoral response, etc.) have been shown to differ between
      laparoscopic and open cholecystectomy, and the aim of this study was to
      investigate the effects of laparoscopic and open surgery on the coagulation and
      fibrinolytic pathways. METHODS: Fourteen patients undergoing laparoscopic
      cholecystectomy and 12 patients undergoing open cholecystectomy had blood taken
      in the perioperative period for fibrinopeptide A (FPA) prothrombin fragment F1.2,
      antithrombin 3, tissue plasminogen activator (tPA) and its fast-acting inhibitor
      plasminogen activator inhibitor-1 (PAI-1 antigen and activity), and the
      euglobulin clot lysis time (ECLT). RESULTS: The only significant differences
      between the two groups occurred 6 h after surgery when the ECLT was longer (p <
      0.005; Mann Whitney), and PAI-1 antigen and activity were higher (p < 0.01 and p
      < 0.001, respectively; Mann Whitney) after open cholecystectomy than laparoscopic
      cholecystectomy. CONCLUSIONS: Other changes in fibrinolysis and coagulation were
      similar for open and laparoscopic cholecystectomy. With respect to hemostasis,
      laparoscopic cholecystectomy does not increase the risk of thromboembolic
      complications compared to the conventional procedure.

PMID- 8881055
TI  - Techniques for intrasplenic hepatocyte transplantation in the large animal model.
AB  - BACKGROUND: The preferred therapy for acute and chronic liver insufficiency and
      severe heritable disorders of liver metabolism is whole-organ transplantation.
      However, due to the shortage of organ donors and high cost, alternative
      therapeutic approaches have been proposed, including transplantation of normal
      allogeneic hepatocytes. Recently, it has been reported that many hepatocytes
      transplanted into the spleen migrated to the liver. We therefore carried out a
      series of large-animal experiments to reexamine the intrasplenic route and to
      develop a method for large-scale hepatocellular transplantation in pigs. METHODS:
      Allogeneic porcine hepatocytes were transplanted using the following routes: (1)
      retrograde injection of cells via the splenic vein, (2) intraarterial injection
      of cells, (3) direct intrasplenic injection of cells after laparotomy, (4)
      percutaneous intrasplenic injection of cells under laparoscopic control, (5)
      laparoscopic intrasplenic injection of cells. The number of cells injected varied
      from 2 x 10(9) to 10 x 10(9) cells. RESULTS: Of all the methods tested, only
      direct intrasplenic injection of 2 bln of cells was found to be compatible with
      survival. However, even with this "small" number of cells (2% original liver
      mass), there was a significant risk of spleen infarction, perisplenic adhesion
      formation, and portal vein thrombosis. The laparoscopic approach was found to be
      reliable, simple, and safe. CONCLUSION: Even though the spleen is considered by
      many authors the optimal site for hepatocellular transplantation, transplantation
      of cells in a number needed to support the failing liver may be associated with
      significant complications, morbidity, and mortality.

PMID- 8881056
TI  - Fluoroscopy. A valuable ally during difficult colonoscopy.
AB  - BACKGROUND: This study determines the pattern of fluoroscopy use during
      colonoscopy among a group of gastroenterologists and colon and rectal surgeons
      who have it readily available for each patient. METHODS: One thousand three
      hundred fifty-seven consecutive patients undergoing colonoscopic examination were
      studied over a 16-month period. RESULTS: Fluoroscopy was used during 34% of
      colonoscopic examinations. The frequency of fluoroscopy use was significantly
      higher for women (41% vs 28%, p < 0.001). Fluoroscopy was most commonly used to
      precisely locate the colonoscope tip (45%) or during manipulation of troublesome
      loops of colon (42%), thus accounting for 87% of 677 fluoroscopic checks. The
      most common location of the colonoscope tip during these fluoroscopic checks was
      the hepatic flexure (23%) followed by the cecum (20%); 51% involved the right
      colon. The selective use of fluoroscopy during the more difficult cases was
      substantiated by the longer procedure time (36 vs 26 min) and significantly lower
      cecal intubation rate (74% vs 96%, p < 0.002) when fluoroscopy was required.
      Fluoroscopy also proved to be valuable when precisely locating pathology and
      teaching colonoscope intubation techniques. CONCLUSIONS: Endoscopists who have
      fluoroscopy readily available often use it during difficult colonoscopic
      examinations. Fluoroscopy is most commonly used to maneuver troublesome loops of
      colon or to precisely locate colonoscope tip position, especially when
      negotiating the right colon. Although this technology is more frequently required
      for women, fluoroscopic capability for all colonoscopic examinations is
      advantageous.

PMID- 8881057
TI  - Laparoscopy for chronic abdominal pain.
AB  - BACKGROUND: This purpose of this investigation was to evaluate the utility of
      laparoscopy in patients with chronic abdominal pain. METHODS: A retrospective
      review was performed of 34 patients who underwent laparoscopy for chronic
      abdominal pain. Average patient age was 39 years. The majority were women. Most
      had undergone abdominal surgery in the past. RESULTS: All procedures were
      performed laparoscopically. A positive finding was made in 65% of patients. Fifty
      six percent of patients underwent adhesiolysis, but 26% required no operative
      intervention other than laparoscopic exploration. Notably, 73% of patients
      reported improvement in pain postoperatively, whether or not a positive finding
      had been made on laparoscopy. CONCLUSIONS: This retrospective study suggests
      laparoscopy can identify abnormal findings and improve outcome in a majority of
      selected cases. Recommendations are provided for patient selection. Prior
      abdominal surgery is not an absolute contraindication to laparoscopic exploration
      for chronic abdominal pain.

PMID- 8881058
TI  - Does hormonal function of the tumor influence the outcome of laparoscopic
      adrenalectomy?
AB  - BACKGROUND: Patients with hypertension, with catecholamine hypersecretion, and
      with cortisol excess may associate intraoperative cardiovascular instability and
      postoperative complications. METHODS: To compare the outcome of laparoscopic
      adrenalectomy (LpA) in patients with aldosterone adenoma (11), Cushing's adenoma
      (six), Cushing's disease (four), pheochromocytoma (Pheo) (11), and nonfunctioning
      tumor (five). Intra- and postoperative parameters were studied and in patients
      with Pheo intraoperative catecholamine plasma levels were correlated with
      cardiovascular derangements. RESULTS: Operative time, estimated blood loss,
      hospital stay, analgesic requirements, and time to return to normal activity were
      significantly higher in patients undergoing total bilateral adrenalectomy for
      Cushing's syndrome compared with other groups undergoing unilateral
      adrenalectomy, but these latter groups showed no significant differences among
      themselves in all parameters analyzed. One patient with nonfunctioning tumor and
      another with Cushing's adenoma were converted to open surgery, and two patients
      with Cushing's disease had urinary infection. Isolation of Pheo was associated
      with significant release of catecholamines but not with hemodynamic changes.
      CONCLUSION: LpA may be the most suitable method for removing functioning adrenal
      tumors.

PMID- 8881059
TI  - The movement of mucosal cells of the gallbladder within the peritoneal cavity
      during laparoscopic cholecystectomy.
AB  - BACKGROUND: Tumor dissemination to trocar sites following the removal of a
      gallbladder malignancy by laparoscopic cholecystectomy is well documented. The
      mode of transfer of malignant cells to those sites remains unclear. METHODS: The
      appearance and movement of gallbladder mucosal cells within the peritoneal cavity
      during laparoscopic cholecystectomy was prospectively studied in 15 patients. The
      appearance of cells on laparoscopic instruments, laparoscopic working ports, and
      also within a 5-microm polycarbonate filter, filtering exhaust carbon dioxide and
      attached to one of the main working ports, was noted. RESULTS: Four out of 15
      gallbladders were perforated during cholecystectomy. Operative choledochography
      was performed in 11 of the 15 cases. Glandular cells were found on instruments at
      the end of the procedure in six cases. Cells were also found in two of the 15
      polycarbonate filters and on the laparoscopic ports in two of the 15 cases.
      CONCLUSION: These findings suggest that cellular contamination of the peritoneal
      cavity is frequent during laparoscopic cholecystectomy. This may occur when the
      gallbladder wall is macroscopically breached or when operative choledochography
      is performed, or by microperforation due to the application of crushing
      laparoscopic graspers to the gallbladder wall. Glandular cells adhere to
      instruments in 40% of the operative procedures and may be the main source of
      dissemination of malignant cells through the peritoneal cavity.

PMID- 8881060
TI  - Confluence of the right adrenal vein with the accessory right hepatic veins. A
      potential hazard in laparoscopic right adrenalectomy.
AB  - Confluent drainage of the right adrenal vein and large accessory right hepatic
      veins was encountered during a laparoscopic right adrenalectomy. In a review of
      previous reports of laparoscopic adrenalectomies we found no mention of this
      finding. However, an anatomic study reported that the right adrenal vein joins
      with an accessory right hepatic vein in as many as 22% of individuals. A complete
      understanding of the anatomic variations in the drainage of the right adrenal
      vein is required for the safe performance of laparoscopic right adrenalectomy.

PMID- 8881062
TI  - Delayed recognition of iliac artery injury during laparoscopic surgery.
AB  - Vascular injury is one of the major complications of laparoscopic surgery. Prompt
      diagnosis is crucial for proper management of this potentially life-threatening
      complication. Two cases of iliac artery puncture occurred during operative
      laparoscopy. The injuries were not diagnosed immediately, probably due to the
      initial accumulation of blood in the retroperitoneum. Significant damage to large
      blood vessels may not be readily apparent during laparoscopic surgery.

PMID- 8881061
TI  - A case of choledocholithiasis with an endoclip nidus, 6 months after laparoscopic
      cholecystectomy.
AB  - A 69-year-old man developed obstructive jaundice 6 months after laparoscopic
      cholecystectomy. Endoscopic retrograde cholangiography suggested a common bile
      duct (CD) stone. A second operation was performed, and this revealed a CBD stone
      with an endoclip as a nidus. Since laparoscopic surgery has become a very common
      procedure, endoclips are used more frequently. Therefore, careful surveillance
      and strict follow-up are stressed to avoid CBD stone and various other
      complications caused by endoclips.

PMID- 8881064
TI  - EndoScope: world literature reviews

PMID- 8881065
TI  - Laparoscopic gastrostomy as an adjunctive procedure to laparoscopic
      fundoplication in children.
AB  - Infants and children requiring fundoplication for gastroesophageal reflux
      frequently have significant associated medical problems necessitating placement
      of a gastrostomy at the time of fundoplication. This article reviews the
      techniques, complications, and results of 141 laparoscopic Stamm gastrostomies
      performed in conjunction with laparoscopic fundoplication in infants and
      children. The three techniques employed were the T-fastener technique (63/141)
      which is best utilized in patients with thick abdominal walls; the trocar-site
      technique (53/141) which is technically easy to perform but prone to infection
      and fistula formation; and the U-stitch technique (26/141). General complications
      of laparoscopic gastrostomy include development of gastrocutaneous fistulae
      (2/141), perigastrostomy cellulitis (8/141), and the formation of granulation
      tissue at the gastrostomy site (45/141). The only perioperative death was due to
      a technical error during gastrostomy tube placement. Our preferred method for
      laparoscopic gastrostomy in most children is the U-stitch technique.

PMID- 8881063
TI  - Port-site metastases of adenocarcinoma of the fallopian tube after
      laparoscopically assisted vaginal hysterectomy and salpingo-oophorectomy.
AB  - Port-site metastases following laparoscopic surgery for cancer constitute an
      emerging problem. We report a case of cutaneous metastasis at a port site
      following laparoscopically assisted vaginal hysterectomy and salpingo
      oophorectomy for unsuspected adenocarcinoma of the fallopian tube. This
      complication occurred 7 months postoperatively and was treated with resection. A
      single site was involved. Possible etiologies are implantation from
      "contaminated" instruments or dissemination of tumor cells by the positive
      pressure pneumoperitoneum. Preventive measures include precise and clean surgical
      technique, the use of a nonporous bag, postoperative trocar-site excision or
      irradiation, and conversion to laparotomy either intra- or postoperatively.

PMID- 8881066
TI  - Laparoscopic approach to incarcerated inguinal hernia.
AB  - The safety and effectiveness of laparoscopic treatment for incarcerated inguinal
      hernia have not been clarified. Six patients who underwent laparoscopic reduction
      and repair of incarcerated inguinal hernias were reviewed retrospectively. All
      operations were initiated within 1 h after establishment of the diagnosis.
      Laparoscopically, the incarcerated small-bowel segments could be easily returned
      to the abdominal cavity by a combination of pulling them with Babcock forceps
      while pushing back the bowels from outside the abdominal wall. The hernial
      portals were not cut in three patients, while they were dissected in the other
      three. All incarcerated bowels were congested and red immediately after
      reduction; however, their color returned to normal during hernia repair and
      unnecessary bowel resection was therefore avoided. The mean operation time was 88
      min. Although one patient underwent laparotomy because of the suspicion of
      necrosis of the incarcerated inguinal hernia, which was finally found to be due
      to postoperative paralytic ileus, the postoperative courses of the remaining five
      were uneventful. Laparoscopic reduction and repair of incarcerated inguinal
      hernia was useful, and unnecessary bowel resection could be avoided.

PMID- 8881067
TI  - The abdominal drain. A convenient port for second-look laparoscopy.
AB  - Abdominal reexploration may occasionally be necessary in cases of doubtful bowel
      viability and intra-abdominal sepsis. When this is indicated, second-look
      laparoscopy may be a useful alternative to conventional surgery, because it
      avoids subjecting an often critically ill patient to the trauma and risks of
      relaparotomy. Performing the laparoscopy through a cannula fitted to a flexible
      tube drain, inserted at the first laparotomy or laparoscopy, is proposed. The
      drain is withdrawn slightly, a laparoscopic cannula is inserted into the drain,
      pneumoperitoneum is established, and the laparoscope is then passed down the
      cannula and the drain for exploration. The authors considered this technique in
      11 cases and report four cases in which it was used. Therapeutic laparoscopic
      procedures-e.g., drainage of collections, adhesiolysis, and stroma formation-were
      carried out in two cases, and laparotomy was required in two. This method is
      safe, atraumatic, and technically simple, and it can serve diagnostic as well as
      therapeutic purposes. The simplicity and ease of this method may encourage wider
      application to benefit more patients.

PMID- 8881069
TI  - The author replies

PMID- 8881068
TI  - Bile leakage following laparoscopic cholecystectomy.

PMID- 8881070
TI  - Gastroduodenal polyps in familial adenomatous polyposis.

PMID- 8881071
TI  - The authors reply

PMID- 8881072
TI  - [Public health in social responsibility--social medicine aspects].

PMID- 8881073
TI  - [Public health in social responsibility].

PMID- 8881074
TI  - [In recognition of Prof. Dr. Kurt-Alphons Jochheim on the award of the Salomon
      Neumann Medal of the German Society of Social Medicine and Prevention].

PMID- 8881075
TI  - [1995 Berlin social structure atlas--a planning instrument for health and social
      planning within the scope of administrative reform in Berlin].
AB  - Social unequality and social differences of a population can be defined as social
      structure. The objective of this study is the construction of indices with which
      an analysis of space-related social disparities from their spacious dimensions
      can be made. Each dimension has to be described with a multitude of space-related
      social indicators first, and then identified and calculated with a multivariate
      statistic procedure (Factor Analysis). With the existing analysis basic dates are
      provided. This information about the social situation of Berlin districts as well
      as the resulting political plannings shall contribute to the reduction of
      existing differences, in particular to the reduction of social disadvantages. In
      general, decisions regarding allocation on the private as well as on the public
      sector should be supported by the social structure analysis.

PMID- 8881076
TI  - [Work capacity, severe disability and needs for disability services in Thuringen
      with respect to demographic change].
AB  - Considerable changes are taking place in germany in respect of age groups (fewer
      youngsters, more old people), and this is bound to be reflected by the demography
      of the working population (15 to 64 years) during the next 50 years. It is shown
      in this contribution how the expected changes in age distribution in Thuringia
      will probably be reflected by the number of pensioners who are incapable of
      gainful employment or of exercising their original job for which they were
      trained. The proportion of younger persons who had to be pensioned because of
      inability to work or major disablement or severe need of nursing care, will
      decrease until 2040 A.D., these persons being in most cases about 10 years
      younger than the usual pensioning age. This entails a great need for medical,
      social and job rehabilitation in tremendous measure: a major challenge both in
      sociomedical and labour market policy respects.

PMID- 8881078
TI  - [Risk of hearing loss caused by high volume music--presenting an educational
      concept for preventing hearing loss in adolescents].
AB  - During an one-hour lecture 277 pupils between 16 and 25 years of age, were
      questioned about their hearing behaviour and instructed in the consequences of
      hearing impairment resulting from listening to loud music. Furthermore
      audiometrics were offered and there was possibility to measure the loudness of
      the walkman used. A majority visited "discos" and/or used walkman. Over 80%
      claimed their hearing is good, over 75% knew that loud music can cause damage to
      hearing. The walkman users suffered more frequently from tinnitus and failed to
      hear a door bell more often. After the instruction 75% of the pupils were willing
      to protect their hearing in future. Eight of 89 pupils had a hearing reduction of
      up to 40 dB(A). The average sound pressure level of the walkman was 104 dB(A).

PMID- 8881077
TI  - [Epidemiology of blindness, especially in diabetes--overview of current studies].
AB  - The main targets of the St. Vincent declaration of 1989 and of the WHO programme
      Health for All 2000 are reduction of loss of sight and especially of blindness
      associated with diabetes. However, hardly any data on blindness are available
      that describe a basic situation and would be suitable as a starting point for
      planning interventions and assessing them from the viewpoints of efficacy and
      efficiency. Only few studies have been conducted so far with detailed population
      related data on the incidence and relative risks of blindness, as well as the
      associated mortality. The article reviews these studies and presents
      investigations that are presently being conducted in our department in this
      regard. The results obtained so far point to an increased incidence of blindness
      in peoples with diabetes, high relative and attributable risks especially in the
      young and middle-aged, and increased mortality rates subsequent to blindness,
      compared to the total population.

PMID- 8881079
TI  - [Determining cause of death from death certificates in public health offices-
      experiences with a data custodian model].
AB  - In a study on the long-term outcome after thrombolysis in patients with acute
      myocardial infarction, we had to ascertain the cause of death as noted in the
      confidential section of the official death certificate at the Public Health
      Office. Since current data protection legislation does not permit direct access
      to the death certificates we used a custodian model which strictly separates the
      institution storing the addresses in touch, and carries out the inquiry and the
      institution receiving the anonymised data for analysis. Forty Public Health
      Offices in ten German Bundeslander were asked for causes of death of 118
      patients. Data were delivered by 35 Public Health Offices from nine Bundeslander
      on 106 patients (response = 89.8%). The custodian model which was often proposed
      as a tool for epidemiological research within the restrictive legal framework in
      Germany, proved to be successful in practice, with good response.

PMID- 8881080
TI  - [Innovation, quality and economic efficacy of competitive health care-
      contribution to the "Healthy North Rhine-Westphalia" Project].
AB  - This is a report on what the Provincial Government of North Rhine Westphalia, the
      most densely populated area in Germany, has been doing to ensure that the various
      health establishments (such as, for example, hospitals, nursing homes,
      rehabilitation clinics, and so on) engaged in serving the public, shall act in
      solidarity jointly and severally in striving for maximum innovation, quality and
      efficiency while observing all the rules of competitive fairness. This approach
      was initiated by the Federal German government in 1993 by promulgating a law
      reforming the structural setup of all organisations engaged in health service
      work. From 1996 onward these institutions will be operating within the framework
      of rules ensuring mutual solidarity on a competitive basis. The general trend is
      to increase self-administration and a wider scope of activities and creative
      initiative based on imagination and economy, the latter becoming increasingly
      imperative to avoid wasteful working. In other words: By encouraging competition
      directed at a maximum of innovation, quality and economy, the main targets of
      public health policy will be finally within reach: to maintain the quality
      standards of public health services, to promote general access to these services,
      and also to provide a sound financial basis for them.

PMID- 8881081
TI  - [Cost-benefit analysis of practical occupational medicine service].
AB  - Cost problems in business, industry and government service force everyone to
      probe into the economy of traditional patterns of work and procedures.
      Occupational medicine is no exception. However, there has been a lack of criteria
      for assessing the economic aspects of occupational medicine. We are therefore
      suggesting an approach. Caring for the "human capital" factor is a cornerstone of
      free socioeconomy. Workers should not only be suitably qualified for their job
      but there must be the smallest possible minimum of absenteeism. Occupational
      medicine can do something to positively influence the following factors: by
      preventing incapacity to work by preventing job accidents and professional
      diseases by reducing the time required to cover distances between or within
      workflow phases or stages by reducing waste of time by waiting. Model
      calculations, based on highly plausible basic postulates, show that fully
      integrated occupational medical services are throughout economic and cost-saving.
      Using a concrete example, we arrived at a cost/benefit ratio of 1:2 while
      confining ourselves to benefits attainable within a relatively short time. We
      ignored other, future benefits requiring certain preventive measures, as well as
      other parameters that are difficult to assess, such as corporate identity. At
      present occupational medicine faces a certain amount of identity crisis which
      should not be counteracted by pointing to legislation that justifies its
      existence, but rather by proving that it is indeed highly economical because it
      saves time and money.

PMID- 8881082
TI  - [Social medicine for general practice--initial evaluation of a practice relevant
      teaching concept].
AB  - The form and contents of lectures in social medicine as part of medical studies
      have caused controversy for some time. In the winter term of 1992/93 a new
      concept of main lectures in social medicine oriented to medical practice was
      introduced at the Friedrich-Alexander University of Erlangen-Nuremberg. In
      particular, these lectures deal with primary medical topics relevant to social
      medicine, interspersed with case examples, visits to patients and excursions. As
      a means for students to express critism of the lectures offered, at the end of
      the summer term of 1994 an evaluation of university tuition was first carried out
      using an anonymous, standardised questionnaire. Fifty-five of the 179 students
      registered for the lecture, studying in terms 7 to 12, took part in the survey.
      Among the regular lecture-goers there was a high acceptance of the concept and
      presentation of the lecture contents in 75% of those asked. This was not found to
      be dependent on sex or on how far the students had progressed in their studies.
      Despite interest in social medicine in 80% of cases, for the vast majority of
      those asked the subject does not yet play any role as a future field of research
      or occupation. While 60% of the participants in the questionnaire accorded
      sociomedical topics an important rank in the study of human medicine, 35%
      regarded an independent chair for social medicine, against the background of over
      full timetables, as unnecessary. On the other hand, the practical relevance and
      usefulness of what is taught was regarded by 72% as high. Despite a general lack
      of enthusiasm for lectures the practically-oriented approach has obviously
      succeeded in making clear to the students the importance of sociomedical topics
      in routine medical practice.

PMID- 8881083
TI  - [Prevention of osteoporosis: estrogen substitution paradigm].
AB  - There is an increasing belief among most physicians that hormone replacement
      therapy (HRT) is unquestionable efficacious to prevent osteoporotic fractures in
      women after the menopause. However, an analysis of the studies which are regarded
      as efficacy proof of HRT concerning the prevention of hip fractures--as the most
      important manifestation of osteoporosis--shows that the data are weaker than
      generally assumed: there are no randomised trials with regard to hip fracture
      prevention by HRT and the protective effect which is seen in the observational
      studies is inversely related to the methodical state of the respective type of
      study. Consequently, a bias cannot be excluded, while the so-called 'selection-by
      health'-bias could play an outstanding role. For the efficacy proof of a
      treatment randomised controlled trials cannot be replaced by results of
      observational studies, however impressive they may be.

PMID- 8881084
TI  - [Social medicine evaluation and rehabilitation in diabetes mellitus].

PMID- 8881085
TI  - SCAN and the PSE tradition.
AB  - The development of a series of instruments that has so far culminated in SCAN
      version 2.0 began in the late 1950s because of the need for better tools for
      clinical measurement (including categorization and diagnosis). The basic
      principles of the PSE had long been decided by the time of first publication in
      1974 and have remained the same since. Based on the glossary of differential
      definitions, the aim is to provide comprehensive, accurate and technically
      specifiable means of describing and classifying clinical phenomena in order to
      make comparisons. Insofar as it fulfils this aim, SCAN can be used to enhance
      clinical work and education and advance knowledge through its use in biomedical,
      epidemiological and psychosocial research.

PMID- 8881086
TI  - Psychiatric assessment instruments developed by the World Health Organization.
AB  - Over the past 30 years the World Health Organization (WHO) has produced a number
      of assessment instruments intended for national and cross-cultural psychiatric
      research. WHO instruments have been tested and used in many collaborative studies
      involving more than 100 centres in different parts of the world. This article
      reviews the main WHO instruments for the assessment of (a) psychopathology, (b)
      disability, quality of life and satisfaction, (c) services, and (d) environment,
      and risks to mental health. The principles used in the development of WHO
      instruments, their translation and their use across cultures and settings are
      discussed.

PMID- 8881087
TI  - Mental health care costs: paucity of measurement.
AB  - For an evaluation of a mental health care programme to be comprehensive, it
      should include an economic component. However, very few cost instruments appear
      to exist, and only one has been fully described in the literature. This paper
      seeks to review the studies where costs have been calculated. For this exercise
      to be facilitated the different elements which make up overall cost are
      described. A number of areas have experienced economic evaluations, and the more
      important studies are described. The paper concludes that all too often
      evaluations either fail to measure costs or do so in an incomplete and
      inappropriate way.

PMID- 8881088
TI  - Measures of quality of life among persons with severe and persistent mental
      disorders.
AB  - In order to provide clinicians, researchers, program evaluators, and
      administrators with current information on the assessment of humanistic outcomes
      of services for persons with severe and persistent mental illnesses (SPMI), the
      literature on measuring quality of life (QOL) for these persons is summarized.
      The literature on QOL assessment procedures up to the end of October 1992 for
      persons with SPMI is reviewed, covering QOL measures that at a minimum assess
      subjective well-being. Measures are summarized according to purpose, content,
      psychometric properties, patient subgroups with whom used, and key references.
      Ten QOL measures are summarized and reflect considerable variability on the
      parameters examined. Comprehensive, reliable, and valid measures of QOL are
      available although further development of QOL assessment methodologies is needed.
      More importantly, we must strive for a better understanding of how to interpret
      and use QOL outcome information.

PMID- 8881089
TI  - Quality of mental health service care: the forgotten pathway from process to
      outcome.
AB  - The validity of the concept of outcome depends on a relationship between routine
      treatment and later health status. Outcome evaluations and audits are very rare
      in psychiatry. A substantial expansion in epidemiologically based, naturalistic,
      observational, process-outcome data collection in routine psychiatric practice is
      essential in order to identify treatment allocation biases and other reasons for
      unexpected outcomes. Identified causes of undertreatment should lead to locally
      agreed detailed clinical guidelines. Experimental evaluation should take place in
      routine clinical practice settings, with change in both process and outcome as
      the objective. Ultimately, the results of both experimental and observational
      outcome studies on representative service users should converge, permitting
      outcomes to be the ultimate arbitrator of quality.

PMID- 8881090
TI  - Treatment of bulimia nervosa: when CBT fails.
AB  - Controlled studies have established manual-based cognitive-behavioral therapy
      (CBT) is the first-line treatment of choice for bulimia nervosa. Nevertheless,
      its effectiveness is limited. On average, only 50% of patients cease being eating
      and purging. Of the remainder, some show partial improvement, whereas a small
      number derive no benefit at all. In treating nonresponders to CBT one option
      would be to use antidepressant medication. A second would be to adopt
      interpersonal psychotherapy (IPT), an alternative psychological therapy with
      empirical support. However, both options have failed to reduce binge eating
      following unsuccessful CBT. Treating nonresponders is hampered by the lack of
      treatment-specific predictor variables. Comorbid personality disorder is
      associated with a poorer response not only to CBT but also alternative therapies.
      There is no evidence that psychodynamic therapy is effective with complex cases
      with associated psychopathology. A third option is to use more expanded or
      intensive CBT. An example of the latter would be concentrated exposure within an
      inpatient setting. The relative merits of adhering to manual-based treatment
      versus allowing therapists free reign in individual case formulation are
      discussed.

PMID- 8881091
TI  - Exposure versus cognitive restructuring in the treatment of panic disorder with
      agoraphobia.
AB  - The aim of this study was to assess the rate of change on clinical, behavioral
      and cognitive variables during exposure therapy and cognitive restructuring in
      the treatment of panic disorder with agoraphobia. A total of 28 Ss who received a
      diagnosis of panic disorder with agoraphobia were randomly assigned to either of
      two treatment conditions: exposure therapy or cognitive restructuring. Treatment
      conditions were kept as distinct as possible from each other. Subjects were
      assessed on five occasions: pretreatment, after 5, 10, and 15 (posttreatment)
      sessions of treatment and at a 6-month follow-up. Analyses of outcome data
      revealed strong and significant time effects on all measures. However, no group x
      time interaction reached statistical significance, suggesting that both
      strategies operate at the same pace. Furthermore, power analyses suggest that any
      difference that might exist in the rate of improvement between exposure and
      cognitive restructuring in the treatment of panic disorder with agoraphobia is
      marginal.

PMID- 8881092
TI  - Characteristics of generalized anxiety disorder in older adults: a descriptive
      study.
AB  - Despite the prevalence of Generalized Anxiety Disorder (GAD) in older adults,
      little is known about psychopathological features of excessive worry in the
      elderly. This investigation compared 44 GAD patients (mean age 67.6), diagnosed
      using structured interview, with a matched sample free of psychiatric disorders
      on self-report and clinician measures. Results indicated that GAD in the elderly
      is associated with elevated anxiety, worry, social fears, and depression. Using
      self-report measures alone, near-perfect classification of Ss into groups was
      achieved with four measures (PSWQ, WS-Soc, FQ-Soc, and BDI). Using clinician
      ratings, near-perfect classification was achieved with Hamilton anxiety ratings.
      Comparison of GAD patients whose symptoms began in childhood vs middle adulthood
      revealed few differences on these dimensions. Results are discussed in light of
      features of GAD in the elderly, highlighting implications for further study.

PMID- 8881093
TI  - The expectancy bias model of selective associations: the relationship of
      judgements of CS dangerousness, CS-UCS similarity and prior fear to a priori and
      a posteriori covariation assessments.
AB  - This paper describes three experiments examining predictions from the expectancy
      bias model of selective associations (Davey, 1995). In a simulated 'threat'
      conditioning procedure, Experiment 1 showed that UCS expectancy following both
      ontogenetic and phylogenetic CSs was significantly predicted by: (1) ratings of
      the dangerousness of the CS, perceptions of CS-UCS similarity, and level of prior
      fear to the CS; and (2) ratings of CS-UCS similarity on the dimensions of
      valence, arousal and anxiety. Experiment 2 used a covariation assessment
      procedure which confirmed the findings of Experiment 1, and also showed that both
      phylogenetic and ontogenetic fear-relevant CSs exhibited both a priori and a
      posteriori covariation biases. Experiment 3 found that Ss high and low in fear to
      a fear-relevant CS exhibited a significant a priori UCS expectancy bias, but this
      bias was significantly larger in high fear Ss. Only high fear Ss exhibited an a
      posteriori covariation bias. These results are consistent with predictions from
      the expectancy bias model.

PMID- 8881094
TI  - Cognitive and performance-based treatments for panic attacks in people with
      varying degrees of agoraphobic disability.
AB  - Compared the effectiveness of cognitive therapy and performance-based exposure as
      treatments for panic attacks. Subjects were 48 panicky individuals selected
      without regard to agoraphobic disability, and who varied widely in that respect.
      Subjects were assigned randomly to either cognitive treatment, performance-based
      exposure treatment, a combined cognitive/performance treatment, or a no-treatment
      control condition. All three treatments led to marked and enduring improvements
      in panic, and did not differ from one another in effectiveness, whereas the
      control condition produced little benefit. However, on several measures of phobia
      and panic-related cognitions, performance exposure was significantly more
      effective than cognitive therapy. Degree of agoraphobic disability had a
      significant bearing on panic treatment effectiveness. Whereas 94% of the low
      agoraphobia Ss were free of panic after treatment, only 52% of the high
      agoraphobia Ss became panic-free. The findings suggest that when panic treatment
      research excludes people with serious phobias, as it has routinely done in recent
      years, an overly positive estimate of panic treatment effectiveness can result.

PMID- 8881095
TI  - The role of parental fearfulness and modeling in children's fear.
AB  - The present study investigated the contribution of parental modeling to the
      fearfulness of children. Forty children (aged 9-12) who were referred to an
      outpatient treatment centre filled out the trait version of the Spielberger State
      Trait Anxiety Inventory for Children (STAIC) and the revised version of the Fear
      Survey Schedule for Children (FSSC). The parents of the children completed adult
      versions of the STAI-trait and the FSS. In addition, parents rated to what extent
      they generally expressed fears to their children. Results showed that trait
      anxiety in children was positively associated with trait anxiety of both the
      mother (r = 0.34, P < 0.05) and the father (r = 0.31, P < 0.05). Fearfulness of
      the children was only related to fearfulness of the mother (r = 0.56, P < 0.001).
      Most importantly, the data showed that modeling played a role in this
      relationship. A linear association between FSSC scores and mothers' rating of
      expressing fears to their children was found. That is to say, children of mothers
      who never expressed their fears had the lowest FSSC scores, children of mothers
      who often expressed their fears had the highest FSSC scores, whereas children of
      mothers who sometimes expressed their fears scored in between.

PMID- 8881096
TI  - Chronic nailbiting: a controlled comparison of competing response and mild
      aversion treatments.
AB  - Recent studies have suggested that competing response, an abridged version of
      Azrin and Nunn's (1973) habit reversal method (Behaviour Research and Therapy,
      11, 619-628), is a key component in the treatment of chronic nailbiting (Horne &
      Wilkinson, 1980, Behaviour Research and Therapy, 18, 287-291; Silber & Haynes,
      1992, Behaviour Research and Therapy, 30, 15-22). This study replicated and
      extended the latter by adding an 8 week follow-up period and by using a non
      student sample. Forty-five chronic nailbiter Ss were divided into three
      experimental groups. One method involved the use of mild aversion in which Ss
      painted a bitter substance on their nails. A second method required the subject
      to perform a competing response whenever they had the urge to nailbite or found
      themselves biting their nails. Both methods included self-monitoring of the
      behaviour and a third group of Ss performed self-monitoring alone as a control
      condition. The study lasted 12 weeks. Mild aversion resulted in significant
      improvements in nail length, with the competing response method just failing to
      show significance in this regard. There was no significant improvement for the
      control group. The implications for further study and the benefits of competing
      response in the light of these findings are discussed in terms of treatment
      success and use of therapist time.

PMID- 8881097
TI  - Panic disorder or social phobia: which is worse?
AB  - Twenty-eight patients with panic disorder (PD) and 30 with social phobia (SP)
      were compared on demographic and psychopathology measures. The demographic
      comparisons showed that, although people with SP were better educated, they were
      more likely to be single, living alone, and unemployed. The comparisons of
      psychopathology showed that the proportion of people with PD and SP with a life
      time major affective disorder did not differ, nor did the two groups differ on
      the proportion of Ss reporting past suicide attempts. However, a greater
      proportion of patients with SP had Brief Michigan Alcohol Screening Test scores
      above 5, indicating alcohol abuse problems. The implications of these findings
      are discussed.

PMID- 8881098
TI  - Spider phobia questionnaire for children (SPQ-C): a psychometric study and
      normative data.
AB  - The purpose of this study was to develop a reliable and valid questionnaire to
      assess spider fear in children. The Spider Phobia Questionnaire for adults was
      adapted for children by simplifying items and by assessing situations relevant to
      children. The SPQ for children (SPQ-C) was administered to two non-clinical
      samples of children aged 8-12. The first sample consisted of 586 Ss who filled in
      the SPQ-C twice, with a retest interval of 6-7 weeks. Internal consistency and
      test-retest reliability were high. The second sample consisted of 669 children of
      which 28 spider phobic and 30 nonphobic girls were selected for the Behavioural
      Approach Test (BAT). The SPQ-C predicted BAT scores, thus supporting the validity
      of the questionnaire as a measure of spider fear. Norms for the SPQ-C, based on
      the total sample of children, are provided.

PMID- 8881099
TI  - Validation of the spanish version of the Anxiety Sensitivity Index in a clinical
      sample.
AB  - In this study we validated the Spanish version of the Anxiety Sensitivity Index
      (ASI) in a sample of anxiety disordered patients. The results revealed that: (1)
      ASI scores were higher for anxiety disordered patients than for normal control
      subjects, and higher for patients with panic disorder (PD) than for patients with
      other anxiety disorders (OAD). In contrast, there were no differences among the
      groups on the Cognitive-Somatic Anxiety Questionnaire (CSAQ). (2) Using
      discriminant analysis, we were able to differentiate PD patients from patients
      with OAD on the ASI, but not on the CSAQ. (3) Results supported a unidimensional
      factor-structure for the ASI. (4) Data provide cross-cultural evidence for
      construct validity and concurrent validity of the Spanish ASI, and provide
      further evidence for the usefulness of the concept of anxiety sensitivity.

PMID- 8881100
TI  - [Hematopoietic growth factors: general presentation].
AB  - Modern molecular haematology is characterized by the great strides made in the
      use of cytokines, especially haematopoietic growth factors (HGFs). These factors
      constitute a heterogeneous group of molecules that ensure the survival,
      proliferation and differentiation of the haematopoietic cells. Present detailed
      knowledge of the structure of the chief HGFs and their receptors, and of the
      cloning and sequencing of their genes, permits the use of genetic engineering to
      produce recombinant human growth factors whose therapeutic applications have
      raised very great hopes for clinical haematology. However, it should not be
      forgotten that these HGFs, which are very costly, are powerful two-edged weapons
      capable of triggering a cascade of reactions, and have a field of activity that
      often goes beyond the single highly specific property which it is hoped they
      possess. The risks and costs of their use are currently being evaluated.

PMID- 8881101
TI  - [Physiology of eryhtropoietin and its therapeutic use].
AB  - Erythropoietin (Epo) is a glycoprotein produced primarily by the kidney and is
      the factor regulating the red blood cell production. Unlike most of the
      hematopoietic growth factors, Epo is principally produced by a single organ, the
      kidney, and is regulated by a classic feedback control system. Epo acts on the
      erythroid progenitors after binding to a specific receptor. The gene coding for a
      66 Kd chain has been cloned. This chain belongs to the hematopoietic growth
      factors family. Epo gene was cloned in 1985. The protein coded by this gene is
      heavily glycosylated. Epo production is regulated by renal tissue hypoxia. Cells
      producing Epo in the kidney are a subset of peritubular interstitial cells of
      fibroblastic origin. Epo is now used in clinical applications. Rationale for the
      use of Epo is based on the serum determination of Epo level. Patients with anemia
      of chronic renal failure are routinely treated with recombinant Epo. Two other
      indications are recognized by French authorities: the treatment of anemia of
      cancer patients receiving platin-derived chemotherapy and the use in autologous
      blood donation.

PMID- 8881102
TI  - [Contribution of hematopoietic growth factors and especially in the context of
      grafts of hematopoietic stem cells].
AB  - The growth factor of hematopoiesis, G-CSF and GM-CSF, are now extremely useful in
      stem cell transplantation (SCT). Their main indications are given in this short
      paper. They accelerate hematopoietic recovery and they reduce morbidity and
      mortality after autologous SCT. GM-CSF can protect from hematopoietic toxicity of
      Gancyclovir and can reduce the mortality related to autologous and allogeneic
      graft failure. The combination of GM-CSF, G-CSF and erythropoietin can replace
      autologous SCT after a high dose therapy. G and GM-CSF are used to mobilise
      peripheral stem cells and allow peripheral blood stem cell transplantation. G-CSF
      given after a chemotherapy is able to mobilise Philadelphia negative stem cells
      in chronic myelocytic leukemia patients. Finally allogeneic peripheral blood stem
      cell mobilised by G-CSF in healthy donor is now a new field of clinical trials.

PMID- 8881103
TI  - [Interleukine-3: a multifunctional cytokine].
AB  - Normal hematopoiesis is regulated in part by a variety of growth factors (HGF)
      acting at different stages of cellular maturation. Among the HGF acting on early
      progenitors, Interleukin-3 (IL-3) is one of the first well characterized. This
      cytokine exhibits various biological activities including proliferative effects
      on hematopoietic stem cells as well as regulatory properties on mature elements
      involved in inflammation and late hypersensitivity. Therapeutical use of IL-3 has
      been suggested in various situations involving bone marrow abnormalities,
      chemotherapy during acute leukemias or HIV infections, and bone marrow
      transplantation. Nevertheless, present data concerning such therapeutic studies
      involving IL-3 alone are deceptive. Thus, current investigations are conducted to
      investigate the potential therapeutic effects of HGF combinations that include IL
      3, of or fusion proteins such as IL-3/GM-CSF or IL-3/Epo hybrid molecules.

PMID- 8881104
TI  - [Mpl ligand (thrombopoietin) and platelet regulation].
AB  - After 35 years of research, the physiological regulator of platelet production
      has been isolated and its gene cloned. This discovery originates from studies
      performed with the myeloproliferative leukemia virus (MPLV), a murine retrovirus
      which induces an acute myeloproliferative syndrome in adult mice. MPLV carries in
      its genome the v-mpl oncogene which corresponds to a truncated form the c-mpl
      proto-oncogene. c-mpl encodes a cytokine receptor (Mpl-R) belonging to the
      hematopoietin receptor superfamily. Among the hematopoietic cell lineages, Mpl-R
      is preferentially expressed on late megakaryocyte progenitors, megakaryocytes and
      platelets. The ligand for Mpl-R, called Mpl-L or TPO or MGDF or megapoietin, is a
      glycosylated hormone of 352 amino acids in human which comprises two domains: the
      N-terminus domain shares 50% similarity with erythropoietin and is responsible
      for the biological activity; the C-terminus part is required for secretion.
      Notwithstanding its major action on megakaryocytopoiesis and thrombocytopoiesis,
      Mpl-L also potentiates the action of other cytokines on several hematopoietic
      lineages. Mpl-L/TPO/MGDF, the homeostatic regulator of platelet production, might
      be a useful therapeutical cytokine to treat thrombocytopenia induced in patients
      by chemotherapy.

PMID- 8881105
TI  - [Contribution to the study of phenothiazine detection by inhibition of
      phosphorescence in liquid chromatography].
AB  - Diacetyl, in deaerated solutions, is a major room temperature phosphorescent
      compound. Its phosphorescence quenching is proposed in order to quantify results
      on phenothiazine derivatives. It is established from the luminescent data on
      phenothiazines that diacetyl phosphorescence can be quenched quantitatively by
      these compounds. This detection mode is applied to liquid chromatography
      limitations as well as the mechanism of the quenching are discussed.

PMID- 8881106
TI  - [Factual medicine or how to realise a necessary and deep evolution in the medical
      practice].

PMID- 8881107
TI  - [Factual medicine].
AB  - It is well known that a number of medical interventions are still based on
      personal practitioner impression, non-systematic clinical experience or
      pathophysiologic rationale rather than solid scientific evidence, even when
      available. Evidence based medicine consists in systematically finding, appraising
      and using validated research results as a basis for clinical decision making.
      Access to evidence is essentially provided by randomized clinical trials. One can
      hope that medical practice supported by the best available evidence about
      diagnosis, prognosis and therapy will lead to some improvement in patient care.
      Nevertheless, the field of grey zones is still so large in clinical practice
      (where incertainty is mainly the rule) that evidence based medicine remains for
      the moment a positive mental attitude more than a pragmatic and generalizable
      approach.

PMID- 8881108
TI  - On the need for evidence-based medicine.
AB  - Doctors always seek to base their decisions on the best available evidence. Often
      this evidence represents extrapolations of pathophysiological principles and
      logic rather than established facts based on data derived from patients. The
      advent and proliferation of randomized controlled trials have led to a rapid
      increase in the quantity and quality of clinically valid evidence concerning
      clinical history taking and physical examination, issues of diagnosis, prognosis,
      therapy and other important health care issues. As a result it is becoming
      possible to make explicit much of the implicit non-verbal reasoning of expert
      clinicians, making their clinical reasoning more comprehensible and accessible to
      trainees. The ability to track down, critically appraise and incorporate evidence
      into clinical practice has been named 'evidence-based medicine'. As the quantity
      of valid evidence increases so does the requirement for each of us to develop the
      skills necessary to assimilate, evaluate and make best use of that evidence for
      patients. Often we fail to identify or address our daily needs for clinically
      important knowledge, leading to a progressive decline in our clinical competency.
      When we do seek knowledge traditional sources of information such as journals and
      text-books are often either too disorganized or out of date and we often resort
      to asking colleagues. The need to maintain and expand clinically important
      knowledge has been partially addressed by increasing demands for continuing
      medical education but how might this be best achieved? Recent evaluations suggest
      that three evidence-based medicine strategies help fulfill these goals. They
      include; learning evidence-based medicine, seeking and applying evidence-based
      medical summaries generated by others, and accepting evidence-based protocols
      developed by others.

PMID- 8881109
TI  - [Current data of the science and medical practice: evaluation of the
      discrepancies].

PMID- 8881110
TI  - [Drug prescription and current data of the science: factors of the
      discrepancies].
AB  - Randomized clinical trial is the main source of evidence in medicine. Information
      from clinical trials, however, is limited because only a limited number of
      questions can be addressed with this approach and, in particular, the issue of
      drug effectiveness (in real life) remains unanswered. On the other hand, the
      literature about drug effects (through animal studies, model of effect,
      observational studies, etc) is very large, but provides little scientific
      evidence useful for drug prescription: most studies do not address relevant
      clinical questions or have methodologic problems. In practice, physicians are
      overwhelmed by thousands of new articles among which they have to select the few
      that are useful and valid for their practice. This task is difficult because
      physicians do not have enough time in their clinical activity and they are not
      trained for critical appraisal of the literature. Therefore, they are extremely
      dependent on the diffusion process that selects and synthesizes the information
      for them. Another important factor that has been shown to influence prescription
      is patient's opinion, as one of the main objective for physicians is patient's
      satisfaction. Some physicians also use prescription as a way to terminate a
      consultation or as a medical act independently from the drug which is prescribed
      (drug prescription being part of the physician-patient relationship). At least,
      the absence of real control over drug prescription is considered to be one of the
      main factors explaining the large discrepancy between numerous prescription
      guidelines (from consensus conference or expert opinions) and the reality.

PMID- 8881111
TI  - [Consequences of discrepancies between current data of the science and medical
      practice].
AB  - The target population for drug treatment is composed of all patients likely to
      benefit from it. It is defined on the basis of all the data collected during the
      clinical evaluation of the therapy (on the studied population). The dissemination
      population comprises those patients who are given the therapy once it has been
      released. Several surveys have shown that these two population do not coincide,
      although they should. The consequences of this gap can theoretically be measured.
      However, in order to do such an evaluation, we need relevant indices representing
      the consequences in terms of lack of expected benefit for the patients. We
      constructed models that represent the gap and its impact on life span and
      explored them by simulation. It came out that the consequences can be assessed in
      practice provided that outcome measurement technology is applied.

PMID- 8881112
TI  - Towards effective professional practice.
AB  - Within the limited resources available for health care, it is important to ensure
      that health care professionals provide effective patient care to achieve the twin
      objectives of improvements in patient outcome and the efficient use of resources.
      There are two pre-requisites for effective professional practice: the
      identification of effective health care interventions; and the use of effective
      dissemination and implementation strategies to ensure the adoption of effective
      interventions in practice. Systematic reviews and valid guidelines represent the
      most efficient methods of identifying effective health care interventions. There
      are many different dissemination and implementation strategies; however,
      traditional passive dissemination methods (for example, publication in
      professional journals, mailing practice recommendations to health care
      professionals) are generally ineffective. Greater attention needs to be given to
      co-ordinating active dissemination and implementation strategies to ensure
      effective professional practice.

PMID- 8881113
TI  - [Opposable medical references in perspective].
AB  - We present the French medical references under their double characteristics of
      'conventional' and therapeutic instruments. On one hand, they are conventional
      because they illustrate a phase of the relations between medical organisations
      and the health insurance fund (embodied in 'National Conventions'), of which they
      clearly illustrate the evolution towards the control of medical care. On the
      other hand, the last National Convention stipulates that medical references
      'define medically unnecessary care and prescriptions', thereby being a
      prescription guide or guideline, all the more so as they are compulsory. We
      describe the evolution of the Conventions, and discuss the appropriateness of the
      references as therapeutic guidelines.

PMID- 8881114
TI  - [Integratable message: central problem of communication for therapeutic
      information].
AB  - The aim of therapeutic information is that people who need it have access to data
      of the highest level of evidence. In this context, a message is defined as the
      medium of information. The conditions for an ideal message to the prescriber are
      described: its content, the qualities it must meet, and the functional issues it
      will tackle. An example illustrates the importance of the form of a message. The
      difference between recommendation and message is highlighted.

PMID- 8881115
TI  - [Drug databank and therapeutic information].

PMID- 8881116
TI  - [Evaluation of the prescription quality: hospital databases].
AB  - Hospital databases can be used to evaluate drug prescription quality with the
      help of drug utilization review (DUR). A DUR appraises the appropriateness of
      prescribing by means of explicit criteria established in accordance with evidence
      based data, and then suggests interventions designed to modify prescriber's
      practice. On the one hand, the capacity of the review to show the variations,
      and, on the other hand, the assessment of the impact of interventions implemented
      to correct those variations, depend on the quality of hospital databases. This
      article has two objectives: to identify the required data, both to carry out a
      DUR and to evaluate its outcomes, and to define the essential qualities of
      hospital databases.

PMID- 8881117
TI  - [The Cochrane Collaboration: the need for international collaboration].
AB  - The Cochrane Collaboration has undergone an unexpected growth since its
      inauguration during an international meeting in 1993. This collaboration was
      established in response to the criticisms of a British physician, Archie
      Cochrane, who criticised the medical profession because it had not organised a
      critical summary of all relevant randomised controlled trials. The driving force
      of the collaboration is the collaborative review groups who collect, sort and
      synthesize data concerning treatment efficacy in their particular area of
      interest. The Cochrane Centres and the Field Coordinations help them to do this
      and together the produce the Cochrane Database of Systematic Reviews. The need
      for international cooperation is obvious because the information necessary to
      this system is produced throughout the world, and only some of this information
      is published.

PMID- 8881118
TI  - [Value of the Cochrane Collaboration: the point of view of meta-analysis
      practitioner].
AB  - To-date, most of the meta-analyses performed are exclusively based on published
      data; however, some are based on individual patient data of published and
      unpublished trials. This last method is the reference method, but it is time
      consuming and costly. The quality of meta-analyses is varied and could partly
      explain the criticisms this method is subject to. The Cochrane Collaboration
      could help in the following fields: promotion of registries of trials and meta
      analyses, methodological research on meta-analysis, improvement of trial search,
      trial data storage and pertinence of information in published trials, improvement
      of meta-analysis quality, and dissemination of results. The interventions of the
      Cochrane Collaboration could thus improve the quality and the time performance of
      meta-analyses, reducing expenses and enabling the widespread dissemination of
      regularly updated results.

PMID- 8881119
TI  - [Hierarchies according to the level of evidence of source data, before their
      integration in the synthesis, in the matter of therapeutic efficacy].
AB  - The discipline therapeutic information uses the concept of the level of evidence
      for source data concerning therapeutic efficacy, and its ordering before
      integration in syntheses. In this paper we will start by considering the problems
      raised by the definition of the level of evidence in terms of the dimensions it
      covers. We have differentiated three components: clinical pertinance of the
      question asked, the methods used to reply and the quality of the data collected.
      Second, we will examine the different criteria important for each of these three
      dimensions. There are many criteria possible which do not all have the same
      weight, and thus for any non-arbitrary tool developed to enable the level of
      evidence to be ordered, it is necessary to know the weight of the different
      criteria. Thirdly, we will present the techniques used for working with
      multicriteria situations in econometrics which represent a methodology we propose
      using to apply in our context. To do so we need to build a 'reference' base for
      the level of evidence using 'experts' opinions which will help us to examine the
      weights of the different criteria. This approach, in conjunction with some
      epistemological and sociological considerations, may contribute to a better
      understanding of the different dimensions of this concept.

PMID- 8881120
TI  - Developing recommendations to promote the uptake of research information in
      clinical practice.
AB  - This paper is aimed at highlighting some often overlooked aspects of the
      development of recommendations for clinical practice, and at addressing some of
      the key factors that can play a role as determinants of the acceptability of
      recommendations in clinical practice by the targeted health care providers. It is
      contended that, even in areas of clinical practice where clearcut recommendations
      could easily be drawn from the available evidence and apparently the issue at
      stake is just to transfer the appropriate message to the targeted audience, it is
      important to acknowledge--from the development stage of the recommendations--the
      complexity and the role of non-scientific key determinants (i.e. beliefs, values,
      vested interests) of clinical behaviour.

PMID- 8881121
TI  - Medication use in seniors: challenges and solutions.
AB  - Use of prescribed and over-the-counter medication increases with age. Although
      drug therapy often results in beneficial effects and improve functional status,
      drug related illness is a significant health problem, accounting for 5 to 23 per
      cent of hospitalization, 1.75 per cent of ambulatory visits and one in 1000
      deaths. In most studies, drug-related illness is more common in the elderly. Four
      factors influence the likelihood that a patient will experience adverse effects
      from a drug: the type of drug prescribed, the characteristics of patients
      receiving the drug, the characteristics of physicians who are prescribing the
      medication, and health care system policy and practice. Cardiovascular drugs,
      psychotropic drugs and NSAIDs are the three groups of drugs that are most
      commonly implicated in drug related illness, probably because they are the three
      groups of drugs that are most commonly prescribed in the elderly. The risk of an
      adverse effect with drug increases with the number of drugs prescribed. Several
      mechanisms may account for this phenomenon including (1) increased sensitivity of
      diseased tissue to drug toxicity (2) potential drug interactions, and (3)
      difficulties in patient compliance with an increasing number of drugs. Physician
      prescribing habits can increase the risk of adverse drug effects through two
      mechanisms: (1) the prescription of drugs that are unnecessary for the treatment
      of ailments that might be better managed through non-pharmacologic management and
      (2) the inappropriate prescription of drugs that are either contraindicated or
      prescribed in combination with other drugs that produce potential drug
      interaction. Errors in prescribing accounting for 19 to 36 per cent of hospital
      admissions due to drug-related events and up to 72 per cent of drug related
      events occurring in the hospital setting. Health care system policies influence
      the list of drugs that are included in the formulary, the conditions under which
      they are accessible and payment policy, all of which strongly influence the
      likelihood that a drug will be utilized. Physician payment policy may also
      influence drug prescribing and the success of initiatives to discontinue drugs.
      Interventions to improve the optimal use of medication will need to target
      policy, patients and physicians. Better information needs to be provided to
      physicians and patients about the risks and benefits of drug therapy, and the
      problems of patient compliance and inappropriate and unnecessary prescribing need
      to be addressed.

PMID- 8881122
TI  - [Role of patient in the medical decision].

PMID- 8881123
TI  - [Note on the necessary definition of therapeutic objectives for optimal
      prescription].
AB  - Prescription of a therapy depends on the patient, his/her condition, and the
      therapeutic goal(s) the doctor has identified. In turn, a therapeutic goal
      depends on the availability of an effective therapy. Without a clearly defined
      objective, a prescription is likely not to be appropriate. The patient may not
      appreciate the importance of good compliance if he/she does not know what it is
      for. The pathway of specialised investigations can include unnecessary tests if
      it is not built up around the objective of identifying the therapeutic goal(s).
      If there is no therapy available, the diagnosis is of no use. The arguments for
      and against a therapy cannot be appropriately assessed and compared if they are
      not put in the perspective of the therapeutic goal(s).

PMID- 8881124
TI  - [Necessity of independence: what kind of independence?].

PMID- 8881125
TI  - [Information system for prescriptors and consumers].
AB  - The efficient dissemination of current research data requires a suitable
      information system and an ideal intermediary as the liaison between the data
      source and the targeted users, i.e. prescribers and consumers. Here we present
      the specifications and possible technical solutions which will enable these data
      to be efficiently transmitted.

PMID- 8881126
TI  - [Reviewing the initial plans for the teaching of pharmacology: quality vs.
      quantity of knowledge, hesitation is no longer possible].
AB  - Pharmacology is located at the intersection of several branches of medical
      education. This position and the exponential development of medical knowledge,
      constrains university professors of pharmacology to make teaching choices, since
      time-limited education is imposed in this subject. Thus, it is necessary to list
      specific educational objectives within a frame of well defined and clear
      hierarchized pharmacological concepts. General and practical pharmacology
      teaching is to be preferred since it provides the knowledge base for further
      acquisition of specialized pharmacology. The necessary data can be easily and
      rapidly taught by means of clinical observations and case reports in connection
      with basic pharmacological concepts and therapeutic strategy. The medical student
      has to acquire rational guidelines for proper drug monitoring. He also has to
      learn how to assess the efficacy of the prescribed treatment and how to supervise
      the compliance. When an adverse effect is observed, the future physician must be
      able to evaluate the benefit-risk ratio. Initiation into the analysis of
      published clinical trials is the best way to develop a critical sense.
      Concurrently, pharmacology teachers should make available technical and practical
      resources to facilitate access to updated scientific data.

PMID- 8881127
TI  - [How to base continuing medical education (CME) on the concepts of evidence and
      decision].
AB  - In order to play its part fully, CME in France must be radically reformed, less
      in its methods than in its philosophy; it is important to ground CME on objective
      evaluation, evidence-based medicine and on medical decision making. These notions
      are often neglected, or even unrecognized, especially in medical education. Asset
      of actual situation are the recent decision of CME legal obligation, which will
      require validation of quality criterion in CME, and large network of associations
      and 'leader-practioners', that would let to most practicing physicians'
      participation.

PMID- 8881128
TI  - [Ulcerous disease and gastritis at the time of Helicobacter pylori].

PMID- 8881130
TI  - [Acute agitation after poisoning to viloxazine].

PMID- 8881129
TI  - [HIV protease inhibitors: general review].
AB  - Protease inhibitors are a new class of drugs which has demonstrated activity for
      the treatment of HIV infection. The function of the HIV protease is to split a
      polyprotein to create smaller proteins which will be incorporated in the
      structure of the virus. The eight cleavage sites of the polyprotein constitute a
      template for the synthesis of potential inhibitors. Today, only inhibitors of the
      Phe-Pro cleavage have shown an antiproteinase activity specific for HIV. Clinical
      trials in HIV infection with saquinavir, indinavir, and ritonavir have
      demonstrated a decrease in viral load measured by plasma HIV-RNA PCR and an
      increase in CD4 lymphocyte counts. The use of protease inhibitors leads to a more
      or less rapid selection of mutant resistant viruses. However, these new drugs,
      either used alone or in combination, constitute a new therapeutic approach for
      the treatment of HIV disease.

PMID- 8881131
TI  - Ultrasound in the diagnosis of injury.
AB  - Ultrasound is one of several modalities useful in the work-up of an injured
      patient. It is a bedside technique which is quick, economical and highly reliable
      in filtering out the patients who are in urgent need of laparotomy. For the
      moment, this is the prime and only function of this modality. The US examination
      can and should be repeated with a very low threshold. Apart from the complication
      rate, which is zero for US, it shares many virtues with DPL. Ultrasonography in a
      badly injured victim is a challenging investigation which should be done by an
      expert. In most situations, this will be a radiologist whose presence in the
      emergency room could further be used for expert film reading and development as
      well as the unhampered implementation of a rational follow-up imaging strategy.
      Follow-up modalities, however impressive, should not be compared with first-line
      investigations. In expert hands, accuracy figures between DPL and US do not
      differ decisively but one must bear in mind that DPL spans only one compartment
      while US gives information about much more vital areas. DPL is complementary to
      US; it is of paramount importance to understand that DPL spoils the US
      examination (and CT as well) but is not hindered by repeated US. DPL can and
      should be used to investigate the nature of free intra-peritoneal fluid when the
      amount does not warrant laparotomy. Neither US nor DPl are substitutes for sound
      clinical judgement.

PMID- 8881132
TI  - Thromboembolic prophylaxis in orthopaedic trauma patients: a comparison between a
      fixed dose and an individually adjusted dose of a low molecular weight heparin
      (nadroparin calcium)
AB  - In a prospective, randomized multicentre trial the safety and efficacy of two
      regimens of a low molecular weight heparin (nadroparin calcium) were compared for
      the prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in
      orthopaedic trauma patients. Two hundred and eighty-three patients with a spinal
      fracture, a pelvic fracture, or a lower limb injury were randomized to receive
      either a fixed dose (7500 anti-Xa IC units = 3075 anti-Xa IU) or a variable dose
      depending on body weight and time since operation (100 to 150 anti-Xa IC units/kg
      approximately equal to 40 to 60 anti-Xa IU/kg). The patients continued the
      prophylactic regimen for 6 weeks, but were withdrawn from the study medication in
      the presence of a major complication or if they were completely cured from their
      injury. To assess the rate of DVT, a B-mode ultrasound scan of both legs was
      performed. Positive results were confirmed by phlebography. If signs or symptoms
      of PE were present, a ventilation-perfusion scan was performed. Both prophylactic
      regimens were equally safe. In each group, five patients developed major
      haemorrhagic complications. In each group, one case of reversible
      thrombocytopenia was seen. DVT was confirmed by phlebography in one patient given
      the fixed dose and in four patients given the variable dose. PE was confirmed by
      ventilation-perfusion scans in one patient with the fixed dose and in two
      patients with the variable dose. An intention-to-treat analysis was performed on
      the overall randomized population, with the assumption that all patients who were
      lost to follow-up had DVT. A therapeutic efficacy analysis was performed on those
      patients, who completed the course of the prophylactic regimen and in whom B-mode
      ultrasound scanning was performed 10 days and also 6 weeks after injury. These
      two modes of analysis showed no significant differences in the incidence of DVT
      or PE between both prophylactic regimens. In conclusion, both regimens were
      equally safe following a spinal fracture, a pelvic fracture or a lower limb
      injury. The risk of DVT and PE was similar with both regimens.

PMID- 8881133
TI  - Intramedullary femoral osteosynthesis: an additional cause of ARDS in multiply
      injured patients?
AB  - This study analysed the effects of reaming and intramedullary nailing and
      thoracic injury related to development of ARDS and multi-organ failure in
      multiply injured patients. Sixty patients were entered into a retrospective
      follow-up study. Twenty-one patients with thoracic injury and femoral shaft
      fracture, treated by intramedullary nailing, were compared with 17 patients with
      a femoral shaft fracture without thoracic injury, and with 22 patients without
      femoral shaft fracture but with major thoracic injury. The incidence of ARDS,
      multiple organ failure (MOF) and the mortality rate in the groups was analysed,
      using chi 2 and Fisher exact tests. No significant differences in age, sex and
      ISS existed between the groups. There were no statistically significant
      differences with regard to the incidence of developing ARDS (P > 0.5), MOF (P >
      0.5) and mortality rate (P > 0.2) after injury. The results of this study suggest
      that reaming of the femoral shaft as part of an intramedullary nailing procedure
      is not a major cause in developing ARDS and MOF in patients with femoral shaft
      fractures and thoracic injury. Conventional intramedullary nailing can be
      considered as a safe procedure in femoral shaft fractures in multiply injured
      patients, as well as in the presence of major thoracic injury.

PMID- 8881134
TI  - Civilian medicine and war: transformation of a health centre to a war hospital in
      Croatia (July 1991-October 1992).
AB  - Organization of the first war hospital (War Hospital Dakovo) in the 1991/1992 war
      in Croatia is presented. During the 13-month period 15123 patients were examined,
      among them 747 wounded. Complete treatment in the hospital was provided for 334
      wounded. Only 23 wounded died immediately after admission, or later on in other
      hospitals. Most wounds were single and caused by shrapnel. Among the wounded,
      75.8 per cent were Croatian soldiers, 22 per cent civilians and 2.2 per cent
      enemy soldiers.

PMID- 8881135
TI  - Roller-blades: should they carry a government health warning?
AB  - Rollerblading is increasingly popular in the UK. Over 12 weeks, we treated 29
      patients of whom 34 per cent required operative intervention. There was a wide
      range of injuries, those of the radius being most common, and some (e.g. femoral
      and pelvic fractures) being quite severe. The value of protective equipment is
      discussed.

PMID- 8881136
TI  - The changing pattern of paramilitary punishments in Northern Ireland.
AB  - Paramilitary punishments in Northern Ireland traditionally involved shooting in
      the limbs with low-velocity handguns. During the recent IRA ceasefire they were
      replaced with beatings by clubs and similar objects. We carried out a
      retrospective review of patients who had suffered punishment beatings who
      presented to the Royal Victoria Hospital, Belfast. Patients were more likely to
      have fractures and more severe soft-tissue injuries. The time spent in hospital
      was often longer, and there was a greater chance of requiring operations (often
      multiple).

PMID- 8881137
TI  - Rupture of the anterior cruciate ligament--a quiet epidemic?
AB  - One hundred and seventeen consecutive patients with 119 anterior cruciate
      deficient knees presenting to a knee clinic were studied to analyse an apparent
      poor diagnosis rate by referring doctors. The diagnosis had been made by the
      original treating physician in only 9.8 per cent of cases. Thirty per cent of the
      patients had been seen by an orthopaedic consultant without the diagnosis being
      made. Thirty-six patients had undergone 51 invasive investigations, including
      arthroscopy, without the diagnosis being made. This was despite 90 per cent of
      patients having a typical history and all having unequivocal physical signs. The
      average delay in diagnosis was 21 months.

PMID- 8881138
TI  - Contoured LCDC plating of the proximal ulna.
AB  - Comminuted fractures of the proximal ulna, particularly in combination with
      dislocation of the radial head, represent complex injuries which threaten both
      elbow and forearm motion. Thirty-seven complex proximal ulna fractures were
      treated with a dorsally applied, limited-contact titanium plate, contoured to fit
      the anatomy of the olecranon and proximal ulna. Twenty-four patients had
      Monteggia fracture/dislocations, and 13 had isolated but complex fractures of the
      proximal ulna. After an average follow up of 24 months, good or excellent
      functional results were achieved in 27 patients.

PMID- 8881139
TI  - Effect of early hip decompression on the frequency of avascular necrosis in
      children with fractures of the neck of the femur.
AB  - Twenty-eight per cent of 32 children with fractures of the neck of the femur
      developed avascular necrosis. It occurred in three of the four type I fractures,
      in five of the 11 type II fractures, in one of the 12 type III fractures and in
      none of the five type IV fractures. We studied the effect of early hip
      decompression on the frequency of avascular necrosis. It had no apparent value in
      type I fractures. To increase the statistical power of our analysis of displaced
      type II and III fractures we combined our cases with similar cases from other
      series. Twenty-two (41 per cent) of the 54 combined cases treated without hip
      decompression developed avascular necrosis while only three (8 per cent) of the
      39 combined cases treated with early hip decompression developed avascular
      necrosis. This difference was statistically significant. This finding supports
      the use of early hip decompression as a means of reducing the frequency of
      avascular necrosis in displaced type II and III fractures. Our findings also
      indicate that the complications of nonunion, malunion and premature closure of
      the proximal femoral physis are minimized by accurate reduction of displaced
      fractures, routine use of internal fixation for all fractures and avoidance of
      permanent physeal damage by internal fixation devices.

PMID- 8881140
TI  - Differing injury patterns in snowboarding and alpine skiing.
AB  - This is a study of all people presenting to ski patrollers with ski and snowboard
      injuries during the 1995 season. There were 476 casualties of whom 396 were
      skiers and 57 were snowboarders. Information was collected retrospectively on the
      mechanism, region and injury, and also personal details of the casualties. The
      information was compared with the numbers of ski and snowboard injuries for the
      1994 season. Injuries due to snowboarding increased in frequency, from 4 per cent
      in 1994 to 11 per cent in 1995. Snowboarders were younger, predominantly male,
      and were more often beginners than were skiers. They most commonly sustained
      ligament strains, dislocations and fractures, with the hand and forearm and
      shoulder most affected. Skiers sustained more ligament strains and soft tissue
      bruising, particularly of the knee and thumb. Snowboarders sustain a different
      pattern of injuries compared with skiers, and this has important implications for
      preventing accidents in the instruction of novices.

PMID- 8881141
TI  - How to avoid overlong screws.

PMID- 8881142
TI  - The effect on patients of non-referral for skull radiography following mild head
      injury.
AB  - This paper assesses the attitude of 705 patients who attended the Accident
      department of a large metropolitan district general hospital, with a mild head
      injury and who were not referred for skull radiography. A questionnaire was sent
      to patients 5-7 months after they had attended. Fifty-one per cent had expected
      an X-ray, and when this did not occur, the majority of this group (63 per cent)
      left the Accident department disappointed. Furthermore, the duration of symptoms
      in this group was prolonged. The introduction of guidelines may reduce clinically
      unnecessary X-ray examinations, but some of the consequences may not be fully
      appreciated. In this study, a significant number of patients were dissatisfied
      with the lack of X-ray referral. The main cause for the associated prolongation
      of symptoms is not clear, but a contributory factory may be that lack of referral
      for radiography led to anxiety concerning the thoroughness of their management.

PMID- 8881143
TI  - Dog bites causing upper-limb fractures in children.

PMID- 8881144
TI  - Fracture of the coracoid process in an adolescent.

PMID- 8881145
TI  - Malrotation of the femur after intramedullary nailing.

PMID- 8881146
TI  - Pelvic ring diastasis and pseudo-diastasis in motorcycle pillion passengers.

PMID- 8881147
TI  - An alternative technique for the use of absorbable mesh in an isolated liver
      injury.

PMID- 8881148
TI  - Recurrent dislocation of a hemiarthroplasty stabilized with an ABC ligament.

PMID- 8881149
TI  - Simultaneous primary closure of four fasciotomy wounds in a single setting using
      the Sure-Closure device.

PMID- 8881150
TI  - Intermittent airway obstruction by a floppy blood clot.

PMID- 8881151
TI  - A case of blunt injury of the inferior vena cava diagnosed by ultrasound and
      managed non-operatively.

PMID- 8881152
TI  - Determination of femoral neck ante/retroversion and pinning angle: a simple
      technique.

PMID- 8881153
TI  - A cannulated pointed awl for femoral intramedullary nailing.

PMID- 8881154
TI  - Femoral neck fracture: a complication of femoral nailing.

PMID- 8881155
TI  - [Small bowell transplantation: shall we continue?].

PMID- 8881157
TI  - [HELLP syndrome].

PMID- 8881156
TI  - [Microalbuminuria].

PMID- 8881158
TI  - [A breath of life and a breath of death in Egyptian papyrus medical texts].

PMID- 8881159
TI  - [Physiology of the anterior pituary gland].
AB  - The anterior pituitary is a complex gland which controls the various peripheral
      endocrine glands (thyroid, adrenal cortex, ovary and testis) as well as essential
      functions as growth, reproduction and lactation. Its physiological role is of
      paramount importance and its pathology multiple, including functional
      dysregulations and diseases caused by lesions or tumors, in particular pituitary
      adenomas. Recent data show that, in addition to the classical control of anterior
      pituitary hormones by hypothalamic neuropeptides and by peripheral hormones,
      local controls of the paracrine or autocrine type exist. Although these new
      findings seem to increase the complexity of anterior pituirary control, they
      might, in the future, shed further light on the physiopathology of this gland.

PMID- 8881160
TI  - [Pituitary adenoma: mechanisms of endocrine oncogenesis].
AB  - Molecular studies on pituitary adenomas support a major role of molecular
      alterations in the pathogenesis of pituitary adenomas. Nevertheless, alterations
      in the neuro-hormonal control of the pituitary could also be involved in
      pituitary tumors formation. The finding that most pituitary adenomas are
      monoclonal has stimulated a search for somatic mutations. For instance,
      activating mutations of the Gs protein, leading to constitutive stimulation of
      the cAMP pathway, have been found in a subset of GH-secreting adenomas. But GHRH
      (growth hormone-releasing hormone) tumoral hypersecretion also stimulates the
      cAMP pathway and causes acromegaly. Pituitary tumor formation might result from
      accumulation of several alterations that would determine the tumoral phenotype.
      The majority of these alterations remains to be found.

PMID- 8881161
TI  - [Acromegaly].
AB  - The diagnosis of acromegaly, in more than 95% linked to a pituitary adenoma, is
      essentially a clinical dysmorphic syndrome. Because of its low evolution, the
      illness is too often diagnosed when complications (cardio-respiratory,
      diabetes...) occur. The biological diagnosis is based on high insulin growth
      factor 1 (IGF1) and growth hormone (GH) levels which are not suppressed under an
      oral glucose load. The treatment is mainly surgical (transsphenoidal selective
      adenomectomy) at first intention. Irradiation and medical treatment (dopaminergic
      or somatostatinergic drugs) are used in case of surgical failure.

PMID- 8881162
TI  - [Prolactin-secreting adenoma].
AB  - Prolactinoma, a benign tumor originating from the lactotroph cells of the
      anterior pituitary, is responsible for signs and symptoms related to both
      hypersecretion of prolactin and tumor mass. Hyperprolactinemia frequently causes
      menstrual cycle disturbances, galactorrhea and infertility in women, sexual
      disorders in men. Microadenomas, characterized by a largest diameter less than 10
      mm, may induce frontal headaches, and macroadenomas (more than 10 mm in diameter)
      may also impair visual function through chiasma compression. Treatment modalities
      include dopamine agonist therapy such as bromocriptine which allows normalization
      of prolactin levels, restoration of gonadal functions and tumor shrinkage in most
      cases. In microadenomas a definitive cure may be achieved by transsphenoidal
      total selective adenomectomy.

PMID- 8881163
TI  - [Cushing's disease].
AB  - Patients with Cushing's disease usually present typical clinical and biological
      features easily leading to the diagnosis. However very atypical presentations of
      the disease do exist especially in the intermittent forms and several
      investigations are often necessary to detect pituitary microadenoma wich
      sometimes is inconspicuous. The course of the disease can be serious and might
      responsible of definitive sequellas wich can threaten patient's life. Therefore
      rapid treatment is recommended. Pituitary surgery should be considered as the
      major therapeutic approach; however, in severe cases or when pituitary-directed
      treatments or OP'DDD have failed, total bilateral adrenalectomy should be
      proposed.

PMID- 8881164
TI  - [Gonadotropic adenomas].
AB  - Since the advent of immunohistochemical and cell culture techniques, the role of
      gonadotroph adenomas in hypophyseal disorders appears more important than
      formerly. A large part of "nonfunctional" adenomas in fact correspond to
      gonadotroph adenomas in vitro. These adenomas raise many clinical and biological
      questions since their presentation is not univocal. In addition, diagnosis of
      these adenomas is important since their spontaneous development leads to neuro
      opthalmological complications, which presently are still too often the revealing
      manifestations of these adenomas.

PMID- 8881165
TI  - [Imaging of pituitary adenoma].
AB  - Direct visualization of pituitary parenchyma and lesions has been made possible
      by progress in imaging. CT scan and magnetic resonance imaging, which has become
      the imaging method of choice in pituitary diseases, allow detection of 2 to 3 mm
      pituitary microadenomas, with a sensitivity of 60 and 85% respectively. The
      ability to establish the extent of the tumor using these techniques has made them
      indispensable to preoperative assessment of macroadenomas. Nevertheless,
      cavernous sinus involvement is often difficult to evaluate, and the smallest
      adenomas still escape detection.

PMID- 8881166
TI  - [Medical treatment of pituitary adenoma].
AB  - Dopamine agonists are able to restore ovulatory cycles in 80-90% of
      hyperprolactinemic patients and to reduce tumoral volume (often dramatically) in
      80% of macroprolactinomas. Their side-effects will be reduced with the use of
      parenteral forms or new agonists currently in preparation. Somatostatin analogues
      administered either subcutaneously by three daily injections (octreotide) or
      intramusculary with a long-acting formulation every 10-15 days (lanreotide) are
      able to "normalize" GH levels in 70% of acromegalic patients and to shrink tumor
      in half of the patients. Side effects are generally minor but an increased
      incidence of gallstones has been reported. These somatostatin analogs are also
      very effective in the treatment of TSH-secreting adenomas. Medical treatment of
      other pituitary adenomas is much more disappointing.

PMID- 8881167
TI  - [Surgery of pituitary adenoma].
AB  - The transsphenoidal approach is used in 99% of pituitary adenomas cases. In this
      kind of surgery, mechanical and endocrinological complications are rare. The
      visual disturbances of the huge macroadenomas are easily cured if the patient is
      operated on before optic atrophy. In secreting adenomas the cure of the
      hypersecretion depends mainly on the tumor size and is obtained in 90% or 95% of
      microadenomas. Recurrencies may occur in 10% or 15% of patients; if they are
      easily diagnosed in hypersecreting tumors they must be systematically searched
      for in ron secreting adenomas which require a regular follow-up.

PMID- 8881168
TI  - [Epidemiology of communicable diseases. Methods of surveillance, notification,
      investigation of epidemics in a community and preventive measures].

PMID- 8881169
TI  - [Pneumothorax. Diagnostic orientation (and management in emergency)].

PMID- 8881170
TI  - [H1 and H2 histamine antagonists. Principles and rules of use].

PMID- 8881171
TI  - [Polynucleosis. Diagnostic orientation].

PMID- 8881172
TI  - [Urinary lithiasis. Etiology, diagnosis, development, prognosis, treatment].

PMID- 8881173
TI  - [Intensive chemotherapy with hematopoietic stem cell autograft in solid malignant
      tumors in children: current evaluation and prespectives].

PMID- 8881174
TI  - ["I accuse"! Is the small height yet acceptable?].

PMID- 8881175
TI  - [Characteristics of head trauma in children: epidemiology and a 5-year follow
      up].
AB  - BACKGROUND: Accidents are the major cause of morbidity and mortality in children.
      The aim of this population-based study was to describe characteristics of head
      injuries leading to hospitalization in children less than 15 years old, in a
      defined geographic population (Aquitaine: 2.7 millions inhabitants) and the
      longterm outcome (5-year follow up) of a sample of these patients. PATIENTS AND
      METHODS: Hospitalized patients, residents of the region, were included in a
      prospective study during 13 weeks spread over the whole year in 1986 in all
      emergency services of the region. The follow-up study concerned patients
      hospitalized in 3 hospitals (a trauma I level center, a pediatric hospital and a
      general hospital), with a sampling frame taking into account the overall injury
      severity. Impairments, disabilities and handicaps were assessed with a structured
      questionnaire five years later and results in children compared with those of
      adults. RESULT: Annual incidence of hospitalized head injuries in children was
      294/100,000 inhabitants. The lethality was 0.3% in hospitalized patients. Ninety
      two percent of head injuries were minor. In the youngest patients, the most
      frequent circumstances were a fall at home. The traffic accidents rate increased
      with age from 14% to 53% in the 10-14 years old children. Five years later, 104
      children were reviewed (83 minor and 21 moderate or severe head injuries).
      Children complained less often of somatic symptoms than adults. Two children had
      disabilities in daily life activities, including one whose minor head injury
      eventually worsened and one after a very severe brain injury. According to the
      Glasgow Outcome Scale three patients had a poor recovery (2 severe and 1 moderate
      disability). CONCLUSIONS: Origin and mechanisms of head injuries in childhood
      were similar than in previous studies. Incidence was higher because of a higher
      proportion of minor head injuries. Disabilities and poor recovery happened in
      children with brain lesions or in one children with a minor head injury
      complicated by a severe anoxia. Anxiety and depression should be better studied
      in these children.

PMID- 8881176
TI  - [Contribution of post mortem skull scanning for the study of sudden infant
      death].
AB  - BACKGROUND: Despite post-mortem examination and autopsy, many cases of sudden
      infant death (SID) remain unexplained. The aim of this study was to assess
      usefulness of CT-scan in the Sudden Infant Death Syndrome (SIDS). POPULATION:
      Twenty-three cases of SIDS had a post-mortem CT-scan evaluation of skull and
      brain. The pictures were retrospectively reviewed by several independent
      radiologists who were unaware of the circumstances of death and results of
      autopsy. RESULTS: Aspects of pneumatocele, probably due to lumbar puncture were
      found in 6 cases. The subarachnoid spaces appeared inexplically hyperdense, as
      they were not correlated to the results of lumbar puncture and autopsy. The
      ventricles were normal in size or density. Density of the dural sinuses
      (superfical and deep) was often increased, an aspect possibly artefactual, due to
      post-mortem thrombosis. The cerebral parenchyma was often slighty hypodense;
      microcalcifications due to congenital toxoplasmosis were found in one case.
      CONCLUSION: There was no correlation between the CT-scan imaging and the delay of
      death and lumbar puncture. Infants with or without subarachnoid hemorrage had the
      same CT scan findings. The CT-scan has a poor value when autopsy is performed; in
      its absence, it could be useful for diagnosing post-traumatic intracerebral
      hematoma.

PMID- 8881177
TI  - [Current aspects of sickle cell disease in children in Gabon].
AB  - BACKGROUND: Clinical manifestations and course of sickle-cell anemia are
      variable. Knowledge about the factors, possibly geographic, that influence
      prognosis are still scanty. POPULATION AND METHODS: Data of hospitalization and
      management of children with sickle-cell disease were studied during two years
      (1992-1993) in the Pediatric Unit of Libreville Hospital. They concerned 205
      admissions of 171 children and 131 outpatients. RESULTS: The main causes of
      hospitalization were: acute anemia (36 cases before the age of 5 years); painful
      crisis whose frequency increased with age (23% before 5 years, 35% between 5 and
      10, 42% after 10 years); infections, essentially pulmonary occurring early, and
      bone infections at any age. Eight children died (because a complication of their
      disease). Among the 131 outpatients, half were detected because pyrexia, anemia
      and/or more often "hand-foot syndrome". More than 60% had hepatomegaly, one third
      still had splenomegaly after five years of age and more than one third was
      icteric. More than half children older than ten years had growth disorders. Mean
      hemoglobin level was 7 g/dL. 21 of the 83 tested children for HBsAg were positive
      and only one out of 79 was positive for HIV. CONCLUSIONS: Clinical manifestations
      and course of sickle-cell anemia in our patients are similar to those reported in
      Congolese children. Genetic and environmental factors may be responsible for
      differences with children from other, in particular French, cohorts.

PMID- 8881178
TI  - [Modality of use of vitamin K in France in newborn infants].
AB  - BACKGROUND: Because of the risk of hemorrhagic disease of the neonate secondary
      to vitamin K deficiency, it is generally agreed that neonates should be given
      vitamin K. There is however, no consensus concerning the route of administration,
      dose, number of doses, or dose frequency. It was therefore necessary to determine
      patterns of vitamin K administration in France. POPULATION AND METHODS: Routine
      vitamin K administration was studied in 1993 by questionnaires sent to all
      maternity units in France. RESULTS: Six hundred and forty of the 1,086
      questionnaires could be analysed. Vitamin K was never prescribed in 0.3% of
      maternity units and was given only to high risk neonates in 3%. In healthy
      neonates receiving milk formulas, the route of administration (oral or IM) agreed
      with the recommendations of the French Committee of Pediatric Nutrition. In
      contrast, breast-fed infants were given IM vitamin K in only 19% of the maternite
      units whereas regular weekly doses were prescribed in only 56%. In premature
      infants, IM doses were prescribed in only 46% of cases and repeated weekly doses
      in 34%. The dose generally prescribed (5 mg orally or IM) was not the recommended
      dose. Among the available products, oral or parenteral vitamin K Roche was the
      most frequently prescribed. CONCLUSION: New recommendations for the use of
      vitamin K in the perinatal period in France are necessary.

PMID- 8881179
TI  - [Leukemia lymphoma T-cell as first manifestation of ataxia-telangiectasia].
AB  - BACKGROUND: Variable degrees of T cell deficiency in ataxia-telangiectasia (AT)
      progressively worsen with time and death from malignant lymphoma is a common
      terminal event. T-cell lymphoma as the first manifestation of AT has never been
      reported. CASE REPORT: A 22 month-old girl born to consanguineous parents, was
      treated for a thoracic T-cell lymphoma and remained in first complete remission,
      with a follow-up of 4 years. Prior to chemotherapy, cytogenetic studies on blood
      showed clonal rearrangements including t(7p;14q), T(2p;7q) and inv (7), while
      karyotype showed 6q- and 1p-mitoses on bone marrow blasts. Hypotonia became
      evident at 3 years. One year later, the neurological status deteriorated. The
      patient presented also severe respiratory tract infections. At that time,
      immunological investigations showed hypo IgG2, very low T4 lymphocytes level, all
      harbouring the CD45 RO phenotype. Increase in alpha-foetoprotein level, the
      ocular movements and the study of DNA synthesis after exposure to gamma-rays
      confirmed the diagnosis of AT. CONCLUSION: In cases of childhood lymphoid
      neoplasia, AT should be considered whenever parental consanguinity, T-cell
      proliferation and/or unexpected toxic therapeutic responses are noted.

PMID- 8881180
TI  - [Association of venous angioma and cavernoma of the posterior fossa].
AB  - BACKGROUND: Association of venous angioma to cavernous malformation is rare. If
      bleeding occurs, it must be assigned to the cavernous malformation. CASE REPORT:
      A 4 year-old boy suffered from an acute ataxia. Investigation showed a venous
      angioma and a cavernoma malformation in the posterior fossa. The patient was
      admitted again at the age of 8 years for a new episode of acute ataxia due to
      cerebellar hematoma. A conservative treatment was settled because of the risk of
      venous infarction. CONCLUSION: Venous angiomas are rarely symptomatic and are
      considered as normal venous variants. Indeed, the cavernomas are true
      malformations with a high bleeding potential. When both lesions are associated
      and bleeding occurs, only the cavernous malformation has to be removed if
      surgically accessible.

PMID- 8881181
TI  - [Bronchial mucoepidermoid carcinoma: apropos of 3 cases].
AB  - BACKGROUND: Mucoepidermoid carcinomas (MEC) are very rare (less than 20 cases
      reported in the literature) and potentially malignant bronchial gland carcinomas.
      PATIENTS: Three children, two boys (11 and 7 years old) and one girl (5 years
      old) suffered from respiratory symptoms such as cough, recurrent pneumonia and/or
      hemoptysis for 2 to 12 months. Bronchial endoscopy showed a mass into the left
      (two cases), or the right main bronchus (one case). Chest CT scan identified
      local extension, and lung-associated lesions. Histopathological study concluded
      to MEC in the three cases. The patients were treated by segmental bronchial
      resection, completed with left upper lobectomy (two cases), bronchotomy (one
      case). All the tumor could be removed; there was no metastasis. The outcome was
      uneventful with a 8 to 24 months follow-up. CONCLUSION: Bronchial tumors of
      children must be considered in patients with chronic cough, recurrent pneumonia
      and/or hemoptysis and require bronchial endoscopy for their diagnosis.

PMID- 8881182
TI  - [Inaugural acute cholestasis of Kawasaki disease].
AB  - BACKGROUND: Hepatic dysfunction with mild obstructive jaundice occurs
      occasionally in Kawasaki disease. Acute episode of cholestasis as a presenting
      symptom has never been reported. CASE REPORT: A 14 year-old-boy was admitted with
      fever and cholestasis. He subsequently developed the classical manifestations of
      Kawasaki disease. No signs of liver cell injury or hepatic failure were present.
      Bacteriological cultures and seroimmunologic markers for viral infection remained
      negative. There was no ultrasonic abnormality of bile ducts. The child was given
      intravenous gamma globulins and salicylate. The outcome was favourable without
      any cardiovascular complications. CONCLUSION: A persistent febrile cholestasis of
      unknown etiology should evoke the diagnosis of Kawasaki disease.

PMID- 8881183
TI  - [Inflammatory pseudotumor of the orbit and suspected sarcoidosis].
AB  - BACKGROUND: Orbital inflammatory lesions may be due to infection, neoplasia,
      systemic disease such as sarcoidosis or be idiopathic. CASE REPORT: A 13 year-old
      boy had uveitis and symptoms of unilateral periglobular orbital inflammation,
      confirmed by computed tomography. Infection and neoplasia were excluded. The
      serum angiotensin-converting enzyme level (ACE) was normal. Steroids were
      effective but three recurrences occurred with bilateralisation of the lesion.
      Serum ACE level increased making sarcoidosis probable. Moreover renal lesion were
      later found. Outcome was good with a prolonged steroid administration for ten
      months. CONCLUSIONS: Sarcoidosis may be revealed by an orbital inflammatory
      lesion. Steroids are necessary to prevent ocular functional complications.

PMID- 8881184
TI  - [Intrathoracic volvulus of the spleen revealing left posterolateral diaphragmatic
      hernia].
AB  - BACKGROUND: Late-recognized congenital left diaphragmatic hernia may have a bad
      prognosis when it is revealed by perforation or volvulus of the herniated
      viscera. CASE REPORT: A 20 month-old boy was admitted for vomiting and abdominal
      pain. X-rays showed left diaphragmatic hernia and the patient was operated on
      with the diagnosis of volvulus of the stomach. Surgery showed hernia through the
      posterolateral segments of the diaphragm with spleen volvulus into the sac,
      requiring splenectomy before reduction of the hernia and closure of the
      diaphragmatic defect. CONCLUSION: This is the fifth report of ectopic
      intrathoracic spleen with volvulus revealing congenital left diaphragmatic
      hernia.

PMID- 8881185
TI  - [Malnutrition and immunodeficiency in children].
AB  - Our knowledge on relationships between nutrition, immunity and infection has much
      progressed. Malnutrition affects all three defence mechanisms: unspecific
      immunity, cellular immunity and humoral immunity. Any kind of nutriment is
      concerned: nitrogen-caloric nutriments, trace elements, vitamins. Restoration and
      maintenance of a good nutritional status have become imperative in order to stop
      the vicious cercle of malnutrition-infection in infants and children.

PMID- 8881186
TI  - [Ontogenesis of lateralities. A review and attempted interpretation].
AB  - The present paper offers an updated review on lateralization development in
      normal children. Instead of just citing a voluminous litterature, we prefer to
      present an interpretation which perhaps is too synthetic but which tries to go
      beyond the frequent contradictions encountered within experimental studies as
      well as between the studies themselves. Results plead for a double movement in
      the human development, first towards a species-specific asymmetry, then towards a
      differentiated symmetry. We propose different advantages for the development of
      human competencies and for the underlying neuro-behavioural organization:
      asymmetry corresponds to phases in the intrahemispheric cerebral organization and
      symmetry to phases of interhemispheric synergy.

PMID- 8881187
TI  - [Nosocomial infections due to syncytial respiratory virus: which hygienic
      measures].
AB  - Nosocomial respiratory tract infections due to respiratory syncytial virus are
      common among hospitalized children. The overall prevention is based on 3 points:
      prevention of person-to-person viral transmission, infection surveillance and
      staff education. Handwashing is the main protective attitude. Other measures such
      as gloving, gowning and wearing masks and goggles are discussed. Changes in
      hospital organisation during epidemic periodes must also be considered.

PMID- 8881188
TI  - [Treatment of migraine in children].
AB  - Simple migraine attacks are usually controlled by rest and an analgesic
      (acetylsalicylic acid or paracetamol), eventually associated with metoclopramide.
      More severe cases with failure of these measures may benefit from antimigraine
      medications such as ergotamine derivatives. Preventive treatment is only
      indicated in case of frequent (> or = 3 per month) and complicated attacks.

PMID- 8881189
TI  - [Rheumatoid arthritis in Black Africa].

PMID- 8881191
TI  - [The Ames test: application to smokers' urine].
AB  - The Ames test is a rapid and sensitive in vitro technique for detecting mutagens
      by using Salmonella typhimurium hypersensibilized strains. We applied this assay
      to the study of smoker's urine mutagenicity. Eighteen smokers and 18 non-smokers
      were investigated. Statistical analysis showed a significant increase of the
      smoker's urine mutagenicity. The Ames test could be used to determine the
      mutagenicity level of smokers. Moreover, the results suggest the applicability of
      the Ames test to urines of ex-smokers and passive smokers.

PMID- 8881190
TI  - [Protein profile and iron deficiency: value of the study of the albumin
      transferrin couple].
AB  - From a clinical standpoint, the search for iron deficiency is based upon serum
      ferritin. However, serumferritin values may be pathologic in other numerous
      pathological conditions such as inflammation, liver diseases, malignant
      hematologic disorders, hemolysis, etc. Proteic profile combines the analyze of
      proteins variations: protein results are converted in percent of normal values
      referenced for the technique used. It has been suggested that on the protein
      profile, an increase in serum transferrin level compared to a normal serum
      albumin level (DAT: difference albumin-transferrin), appears early in the course
      of iron deficiency. In order to know the value of a pathologic DAT > or = 28% in
      the diagnosis of iron deficiency, we prospectively studied 156 patients
      consecutively hospitalized in an internal medicine department. Iron deficiency
      was defined by a low serum ferritin level. Diagnosis performance (sensitivity,
      specificity, positive and negative predictive values) of different biologic
      markers of iron deficiency (serum iron, saturation of total iron-binding
      capacity, low mean erythrocyte volume) and DAT was compared to the performance of
      low serum ferritin values. With the exception of low serum ferritin (which have
      by definition a specificity and a positive predictive value of 100%), pathologic
      DAT appeared as the best index of iron deficiency with the highest sensitivity
      (67.4%), specificity (97.3%), positive predictive value (91.2%), negative
      predicitive value (87.7%) and diagnosis efficacy (sensitivity x specificity =
      0.66). A pathologic DAT associated to a low serum ferritin level increased the
      diagnosis performance of both tests to 0.72. Diagnosis efficacy of DAT was not
      changed (0.66) in 83 patients with a confounding factor for serum ferritin
      analysis (inflammation, liver diseases, malignant hematologic disorders,
      hemolysis) when diagnosis efficacy of all other tests decreased. There was a
      negative correlation between serum ferritin level and DAT level (r = 0.55; P <
      0.0001). In conclusion, an increase of serum transferrin of more than 28%
      compared to serum albumin on a proteic profile gives a significant benefit for
      the diagnosis of iron deficiency. This benefit increases when data of both DAT
      and serum ferritin are associated.

PMID- 8881192
TI  - [Pleuropulmonary manifestations of systemic vasculitis].
AB  - Pleuropulmonary manifestations of systemic vasculitis are common, polymorphic and
      of ambiguous significance: the same pulmonary lesion may reveal a specific
      manifestation of vasculitis as well as a therapy-induced complication, especially
      infection which may favor per se a flare-up. Two questions will be successively
      studied: what are the pleuropulmonary characteristics of Wegener's
      granulomatosis, Churg-Strauss syndrome, periarteritis nodosa, Behcet's disease,
      Takayasu's disease and temporal arteritis? What are the major adverse effects
      that may occur in the course of a treated systemic vasculitis?

PMID- 8881193
TI  - [Thyroid function and dysfunction in the elderly].
AB  - The consequences of aging function are appreciated in various ways. In fact most
      of the thyroid hormone abnormalities described in the elderly are secondary to
      associated disease or treatments. Health and nutritional status seem to be more
      determinant than age. However, there is an increased prevalence of dysthyroidism
      in the elderly. Symptoms may be misleading and induce severe general
      repercussions. Mild or occult forms of dysthyroidism characterized by abnormal
      TSH levels with normal free thyroid hormone levels are not uncommon. Their
      clinical significance and their prognosis without treatment are still unresolved.
      The frequency of dystrhyroidism during old age and the possibility of a specific
      treatment may be in favour of a screening by a systematic TSH determination in
      elderly patients.

PMID- 8881194
TI  - [Treatment of autoimmune thrombopenic purpura in adults].
AB  - Autoimmune thrombocytopenic purpura (AITP) is a common hematological problem.
      Steroids are the usual first-line treatment but give long-term remission in less
      than 20% of adults. High doses of human intravenous immunoglobulin G (IVIg) can
      increase the platelet count in 70 to 80% of patients, but the treatment is
      expensive and the platelet response usually only transient. Seventy to 80% of the
      adults have the chronic form of AITP (ie, disease duration of more than 6 months)
      that only improves on specific treatment. Splenoctomy is the treatment of choice
      when thrombocytopenia is severe and/or associated with life threatening bleeding,
      as it cures 60-80% of patients. The best treatment for patients with severe
      chronic AITP in whom splenectomy is ineffective or contra-indicated is a
      difficult challenge. In this situation, spontaneous remission is rare and 5% of
      patients will die from hemmorrhage. However, the treatments so far proposed in
      refractory chronic AITP (danazol, vinca alcaloids, azathioprine,
      cyclophosphamide, dapsone, etc) are inconsistently and transiently effective. The
      aim of the treatments in AITP are thus different in the acute and chronic forms
      of the disease. In the acute phase, the treatment should quickly increase the
      platelet count, even if the effect in transient, and aggressive treatments (ie,
      splenectomy, immunosuppressive drugs) must be avoided since spontaneous remission
      is possible. On the contrary, splenectomy is the treatment of choice for chronic
      AITP since it obtains complete persistent recovery in nearly 80% of patients. In
      the case of unsuccessfullness, treatments should then be administered with the
      aim to maintain a "safe" platelet count (> 20 to 30 x 10(9)/L).

PMID- 8881195
TI  - [Diagnostic and therapeutic approach to plasma cell granuloma of the lung.
      Apropos of a case of favourable course under antibiotics].
AB  - Plasma cell granulomas are more often solitary benign tumoral lesions, which need
      early surgery both for diagnostic and therapeutic reasons. The authors report a
      case of multiple plasma cell granuloma, diagnosed on biopsies obtained by
      thoracoscopy, and with a good response to a long-term antibiotic treatment. A
      review of the literature shows that this behaviour may represent an interesting
      alternative to systematical surgery in some cases.

PMID- 8881196
TI  - [Hypercalcemia induced by lactation in 2 patients with treated
      hypoparathyroidism].
AB  - The authors report two cases of hypercalcemia which occurred in hypoparathyroid
      women treated with vitamin D and calcium. A recent literature review suggests a
      major role for parathyroid hormone-related protein (PTH-rP), secreted by the
      mammary tissue, in this phenomenon with obvious implications for clinical
      practice.

PMID- 8881197
TI  - [Primary granulocytic sarcoma of the pancreas: efficacy of early treatment with
      intensive chemotherapy].
AB  - In the absence of systemic chemotherapy after the diagnosis of primary
      granulocytic sarcoma (PGS), all patients will subsequently develop acute
      myelogenous leukemia (AML). The authors describe a case of PGS of the head of the
      pancreas found at laparotomy in a 32-year-old man. The patient received early
      after surgery, two courses of high-dose chemotherapy and, with a follow-up of 2
      years, never developed AML. This rare observation illustrates the necessity of
      further early systemic chemotherapy after surgical excision of PGS.

PMID- 8881199
TI  - [New strategies of vaccination in France in 1995].
AB  - Present strategies for vaccinations are based on new vaccines of classical
      (hepatitis A, influenza, varicella) or modern (hemophilus, hepatitis B)
      conceptions. They include variable schemes according to the vaccinal doses
      (hepatitis A, B, diphteria) or the number of injections (hepatitis A, B, rabies).
      Their goals are eradication (Measles, Mumps, Rubella), or immune maintenance by
      boosters (hepatitis A, poliomyelitis, tetanus). They introduce associated
      vaccines in the vaccinal calendar (diphteria, tetanus, poliomyelitis, pertussis,
      hemophilus b and hepatitis B). They enlarged the area of targeted vaccinations
      for at risk-professions or pathologies and for travellers.

PMID- 8881198
TI  - [Pleural effusion and severe edema of the lower limbs induced by bromocriptine].
AB  - High doses of bromocriptine used for treatment of Parkinson's disease may be
      associated with pleuropulmonary complications. Isolated pleural effusions are a
      rare manifestation as is lower limbs edema are an exceptionally one. We report
      the case of a 67-year-old man, treated since five years by a daily dose of 30 mg
      of bromocriptine for Parkinson's disease, who developed important leg's edema and
      a few months later an exsudative right pleural effusion. No etiologies were
      found. Bromocriptine was discontinued. The evolution was characterized by nearly
      complete resolution of pleural effusion and disparition of lower limbs edema.

PMID- 8881200
TI  - [Individual dose adjustment of high-dose methotrexate in clinical practice].
AB  - Since its discovery in 1948 the clinical applications of methotrexate have
      widened; and in order to overcome resistances to methotrexate, the concept of
      high-dose methotrexate has been proposed. The use of rescue by folinic acid, as
      well as rapid dosage of MTX coupled with pharmacokinetic studies, have permitted
      us to administer an optimum dose of drug, with maximum therapeutic effects, but
      with reduced toxicity. Individual adaptation of posology, calculated using the
      test dose or according to population pharmacokinetic with a Bayesian method of
      parameter estimation (which allows us to adjust the dose of high-dose
      methotrexate during its infusion) permits control of inter and intra-individual
      variations of this drug. After analysis of the different methods proposed, we now
      present the results of 778 courses of treatment by high-dose methotrexate (while
      separating 238 courses for osteosarcoma as these formed a homogeneous group of
      patients). Theoretical maximum concentration and length of infusion were decided
      by physicians, followed by individual adaptation of posology by pharmacologists
      at the sixth hour of infusion of methotrexate. This treatment unites maximum
      security for the patient with no serious side effects (no grade 4 toxicity
      according to WHO classification), while receiving an optimum dose of
      methotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further
      intensified without risk, by administering on average 65% more than the usual
      dose in adults (8 g/m2) and 10% more than the usual dose in children (12 g/m2).

PMID- 8881201
TI  - [Gases and damages].

PMID- 8881202
TI  - [Fludarabine and severe autoimmune hemolytic anemia: a new case].

PMID- 8881203
TI  - [Acute ammonium heptamolybdate poisoning: apropos of a case].

PMID- 8881204
TI  - [Multiple myeloma of long-term survival. Apropos of a case].

PMID- 8881205
TI  - [Anterior rectum resection].
AB  - Anterior resection is the method of choice for the treatment of rectal cancer
      situated in the upper or middle third of the rectum. Hand-sewn and stapled
      anastomosis methods have shown comparable results with regard to the rate of
      leakage. Standardized preoperative bowel preparation, antibiotic prophylaxis and
      a careful surgical technique will lead to a postoperative lethality of below 5%
      and a surgical complication rate below 15%. The main functional problems
      following anterior resection consist of incontinence and bladder and sexual
      dysfunction, but these can be partly avoided by careful surgical preparation.
      There is controversy in the literature concerning the positive effect of a
      protective ileostomy or colostomy. The major principles are: (1) radical
      resection of the tumor, with complete removal of the mesorectum, leaving a
      minimal distal margin of 2 cm, and (2) a meticulous anastomosis technique:
      tension-free, pulsation blood flow, tight.

PMID- 8881206
TI  - [Intersphincteric rectum resection with radical mesorectum excision and colo-anal
      anastomosis].
AB  - The tendency toward sphincter-preserving resection for distal rectal cancers has
      led in recent years to a revival of the technique of coloanal anastomosis (CAA).
      Our experience with intersphincteric resection in combination with CAA was
      reviewed with the aim of assessing morbidity, functional outcome, and cancer
      treatment results. A total of 119 patients treated for primary rectal cancer by
      CAA between 1978 and 1994 were studied retrospectively. Seventy-six percent of
      the tumors were located in the lower third of the rectum. There were 4 (3.3%)
      deaths. The most common postoperative complications were urinary retention
      (13.5%) and sexual dysfunction (17%). There were 10 patients (8.4%) with clinical
      anastomic leaks and 3 patients (2.5%) with symptomatic stricture. General
      complications occured in 33 patients (28%). The mean stool frequency was 2.2 per
      day. Twenty-three percent of patients reported 4 or more stools per day. Fecal
      continence was complete in 69%, incontinence to gas in 10%, minor leak in 17% and
      major soiling in 4%. Urgency occurred in 14% and incomplete evacuation was
      present in 27%. The cumulative local recurrence rate was 8.7%, 5-year survival
      was 71% (Dukes A 100%, Dukes B 89%, Dukes C 48%). Interspincteric resection
      combined with CAA provides excellent treatment for low rectal cancers with long
      term preservation of sphincter function and satisfactory local and distant tumor
      control.

PMID- 8881207
TI  - [Technique and indications for sphincter-saving transanal resection in rectal
      carcinoma].
AB  - Using a transanal procedure, two different operative techniques are possible: the
      TEM technique (Transanal Endoscopic Microsurgery), which is more and more
      accepted in the world as method of choice for the local resection of adenomas and
      carcinomas pT1 "low risk" in the rectum and the lower sigma. The technically
      difficult procedure requires much experience. It should therefore only be
      practiced in centers to reach an acceptable number of clinical cases. In the
      lower third of the rectum, especially in locations close to the dentate line, the
      conventional transanal resection of tumours is also an adequate procedure.

PMID- 8881208
TI  - [Vital preoperative function diagnosis in deep anterior rectum resection].
AB  - Restoration of continuity after deep anterior resection may lead to major
      functional problems. Preoperative functional evaluation of the anal sphincter
      should help to select patients unsuitable for reconstruction and produce more
      objective data for evaluation of new technical procedures. In addition to a
      standardized history of continence and the clinical examination, anorectal
      manometry and endosonography of the sphincter are adequate methods.

PMID- 8881209
TI  - [Local therapy of rectum carcinoma. A prospective follow-up study].
AB  - Local therapy of rectal carcinoma with the method of TEM was performed in 98
      patients during the period from August 1, 1989 to January 31, 1994. 56 of the
      patients had pT1, 27 pT2, and 15 pT3 tumours. There was no lethality. The rate of
      complications, which required operative intervention, was 8%. No lymph node
      metastases were found in the specimens of the patients with pT1 tumours, who were
      re-resected, because the margin of the primary specimen were judged to be not
      free of tumour. In the specimens of the re-resected patients with pT2 carcinomas,
      lymph node involvement was more common than remnants of the primary tumour. Two
      of the patients with local therapy of pT1 low-risk carcinomas developed a
      recurrence so far. A secondary procedure for cure according to oncologic criteria
      could be performed in both cases. In selected cases the local therapy of rectal
      carcinoma avoids the high morbidity and mortality of the classical operation.
      Live quality will be improved, especially if an artificial anus can be avoided.
      In case of a recurrence the chance of a secondary procedure for cure is not to be
      underestimated.

PMID- 8881210
TI  - [10 years experiences with transanal endoscopic microsurgery. Histopathologic and
      clinical analysis].
AB  - The clinical and long-term results encountered from July 1983 to December 1992
      are subject of this study. Contrary to other (transanal and transabdominal)
      surgical treatments the endorectal system permits therapeutic local excisions of
      large, rectal adenomas and early rectal carcinomas of the "low-risk" type within
      the entire rectum with minimal morbidity. A superior or comparable rate of
      adenoma recurrence (4.8%, n = 228) as well as a more favourable operative result
      (complication rate 3.9%; lethality 0.6%; n = 348) can be achieved with the
      transanal endoscopic microsurgery. Under palliative conditions, transanal
      endoscopic surgery is more effective than other conservative treatments in cases
      of circumscribed, non-stenotic carcinomas of the rectum. Thorough surgical
      training is required in order to successfully practice transanal endoscopic
      surgery.

PMID- 8881211
TI  - [Mason paracoccygeal trans-sphincteric approach to the rectum: good outcome only
      in highly selective indications?].
AB  - From 3/1985 until 10/1993, a total of 10 patients were operated using the Mason
      approach. Four patients undergoing resection of flat villous adenomas situated on
      the anterior wall of the lower and mid third of the rectum, and one patient with
      adenoma situated on the posterior wall of the upper third, all of them with
      reconstruction using intact rectal wall portions, enjoyed a smooth postoperative
      course, continence and absence of recurrence. Two patients operated for presacral
      local recurrence following rectal excision and rectal prolapse, respectively,
      suffered recurrence after a smooth early course. Two patients undergoing
      resection of villous adenomas situated on the posterior wall of the lower and mid
      third with reconstruction using denudated muscle wall and one patient undergoing
      segmental resection for radiogenic rectovaginal fistula developed complex fecal
      fistulae. On the basis of these experiences and the pertinent literature,
      indications promising uniformly good results were defined.

PMID- 8881212
TI  - [Surgical therapy of severe colitis].
AB  - Severe colitis, eventually complicated by toxic megacolon, perforation or massive
      hemorrhage still represents a potentially life threatening complication during
      the course of inflammatory bowel disease reaching a mortality of almost 40% if
      not operated in time. From 1.1.1973 until 30.4.1994 22 patients (13 men, 9 women,
      mean age 29 years) with either ulcerative colitis or Crohn's disease of the colon
      were operated on for severe colitis. Indications for operative treatment were as
      follows: 7 patients relapsed conservative medical treatment, 8 developed toxic
      megacolon and in 7 patients perforation occurred. Diagnosis was based on the
      clinical criterias first described by Turnbull. In 11 (50%) cases subtotal
      colectomy with an ileostomy and intrapelvic Hartmann's pouch was performed, in 4
      (18%) patients a Turnbull's procedure was carried out with loop ileostomy and
      colostomies and in 3 (14%) cases a left hemicolectomy and transversostomy was
      applied. In two patients with Crohn's disease an ileocolic resection was done
      because of perforation, one received a subtotal colectomy and ileorectal
      anastomosis and one patient was operated by a right hemicolectomy and ileostomy.
      One patient with ulcerative colitis died, reaching a post-operative mortality of
      4.5%. After an intervall of approximately 18 months in the 16 surviving patients
      with ulcerative colitis an ileal pouch-anal procedure could be done. Of the 5
      patients with Crohn's disease one had to be operated on for recurrence, the other
      patients have been free of recurrent Crohn's disease for a follow-up time between
      3 and 11 years. We conclude, provided early operative treatment is intended, that
      subtotal colectomy with Hartmann's pouch and ileostomy is the procedure of choice
      in patients with severe colitis.

PMID- 8881213
TI  - [Surgical therapy and prognosis of not curatively resectable rectum carcinoma.
      Results of a multicenter study of the Colorectal Carcinoma Study Group].
AB  - The prospective multicenter observation study of the SGCRC found in 1121 rectal
      carcinomas a resection rate of 94.2% with 79.1% curative resections (R0), 3.1% R1
      resections and 11.7% R2 resections. The reasons for non-curative resections were
      multimorbidity preventing tumor resection, distant metastasis or locally advanced
      primary tumors. The prognosis following non curative surgery for rectum carcinoma
      depends on resectability, synchrone distant metastases and R classification
      (according to UICC). Additional therapy (chemo- and radiotherapy) may improve
      short time survival after non-curative resections in presence of distant
      metastases. After non-resective surgery local tumor destruction (laser,
      kryotherapy) is possibly an useful additional therapy. The indications for
      multimodal therapies are discussed and the development of uniform therapeutical
      strategies is required.

PMID- 8881214
TI  - [Liver resections of metastases of non-colorectal primary tumors].
AB  - The records of 30 patients who had hepatic resections for non-colorectal liver
      metastases between 1985-1994 were analyzed retrospectively. The perioperative
      morbidity and mortality rates were 7% (2/30) and 3% (1/30). The patient group
      with curative resection (n = 25) was found to have a 5-year survival rate of
      44.6% and a 3-year disease-free survival rate of 19.8%. By univariate analysis,
      the number of metastases and the amount of perioperative blood replacement were
      the only factors that affected survival after curative resection. Synchronous vs.
      metachronous disease was the only factor that showed a significant influence on
      disease-free survival after curative resection. Although the benefit of liver
      resection for non-colorectal metastases is limited, surgical therapy can be
      performed safely and offers some patients a chance of long-time survival.

PMID- 8881215
TI  - [Current therapy of bile duct cysts. I. Extrahepatic cysts].
AB  - A total of 23 patients with extrahepatic biliary cysts (11 type I, 4 type II, 4
      type III and 4 type IVa according to the classification by Todani) seen at our
      institution in a 15-year period were reviewed with emphasis on management and
      long-term results at follow-up of 3 weeks-12 years. Associated hepatobiliary
      disease occurred in 4 patients, including one case with malignant degeneration in
      the cyst 23 years after cystenterostomy, and an association of a gallbladder
      carcinoma with a choledochocele in the other patient. Radical excision of the
      dilated bile duct and reconstruction by Roux-en-Y hepatico-jejunostomy was
      performed in 13 cases (9 type I, 3 type II and 1 type III), combined in 3 cases
      with an antireflux valve. All 13 operated on patients remained in good health for
      6 months to 12 years. These results confirm the need for complete early excision
      of type I, (II) and IVa cysts at all ages before severe complications can occur.
      Endoscopic treatment of type III choledochocele should be limited to the
      management of smaller lesions.

PMID- 8881216
TI  - [Results of occlusion of large or recurrent incisional hernias with
      polytetrafluoroethylene].
AB  - In 48 patients who were suffering from recurrent or large abdominal incisional
      hernias the defect in the abdominal wall was closed by the implantation of a
      patch of polytetrafluoroethylene. Patients were examined 22 months
      postoperatively on the average. In 5 cases recurrence had occurred (10.4%). The
      estimated rate of recurrence two years postoperatively amounted to 14%. As this
      is significantly lower than after conventional techniques without alloplastic
      materials, the closure of incisional hernias by PTFE is an important alternative
      for the management of difficult abdominal incisional hernias.

PMID- 8881217
TI  - [Open laparoscopy for prevention of puncture injuries].
AB  - Perforating lesions occurring during the establishment of the pneumoperitoneum
      using the Veres needle and blind introduction of the camera trocar are among the
      major complications of laparoscopic surgery. Even when all the necessary safety
      measures are observed and despite complete mastery of the technique, this
      complication cannot be completely avoided during the blind procedure. The
      technique of open laparoscopy, so-called, with the introduction of a blunt trocar
      under direct vision is the sole alternative available for the prevention of such
      injuries. The advantages of this procedure are that, with appropriate practice,
      it takes no longer, can be employed in all possible situations, including
      previous surgery, and, in particular, when assisting a surgeon who is in the
      process of gaining experience in laparoscopic surgery. Severe perforating
      injuries and their sequelae are often advanced as an argument against the use of
      laparoscopic surgical procedures. Through the use of open laparoscopy, injuries
      to blood vessels and viscera can be virtually completely eliminated, and patient
      safety considerably improved. On the basis of our own experience, we can
      unreservedly recommend open laparoscopy as the routine approach for all
      laparoscopic interventions.

PMID- 8881218
TI  - [Laparoscopic endoscopic pre-peritoneal combined hernia operation in incarcerated
      indirect inguinal hernia].
AB  - We report on a 73-year-old patient with an incarcerated right sided groin hernia.
      First the incarcerated small bowel was gently retracted laparoscopically; then
      using the extraperitoneal endoscopic approach the hernial sack was redused and a
      15/13 cm prosthesis (polypropylene mesh) brought in appropriate position and
      fixed with endo-staples. Prior to closing the trocar-incisions the vitality of
      the small bowel was checked once again laparoscopically.

PMID- 8881219
TI  - [Acute esophagus variceal hemorrhage and portal vein thrombosis as a complication
      of TIPSS. An unusual emergency indication for liver transplantation].
AB  - Acute oesophageal variceal bleeding is a severe complication of portal
      hypertension caused by liver cirrhosis. The mortality of the first bleeding runs
      up to 50%. Recurrent bleeding deteriorates the long-term prognosis. The therapy
      of first choice for acute oesophageal haemorrhage is endoscopic sclerotherapy. A
      new option to decompress portal hypertension for patients who continue to bleed
      despite sclerotherapy is TIPSS-implantation. We report on a patient suffering
      from recurrent oesophageal haemorrhage caused by portal hypertension due to
      postalcoholic liver cirrhosis, who developed a portal vein thrombosis after TIPSS
      implantation. TIPSS-procedure permitted a bridging period for five months, until
      eventually a severe uncontrollable oesophageal haemorrhage occurred and emergency
      liver transplantation was needed. The patient was discharged after 6 weeks from
      the hospital in excellent condition.

PMID- 8881220
TI  - [Preoperative angiographic marking of angiodysplasia of the small intestine with
      platinum coils].
AB  - In patients with occult lower gastrointestinal bleeding, locating of the source
      of hemorrhage can be quite difficult. While multiple diagnostic tests, like
      arteriography, enteroclysis, nuclear scans, may confirm a small bowel source of
      bleeding, precise localization allowing a directed, conservative surgical
      resection may be problematic. We describe a patient presenting with hemorrhage
      from an angiodysplasia in the small intestine. The preoperative use of highly
      selective angiographically placed platinum coils into the feeding artery allowed
      us to precisely locate the angiodysplasia radiographically during operation and
      to resect a conservative length of small intestine. We believe that preoperative
      bleeding site localization with platinum coils is a simple, effective tool to aid
      surgical resection of small bowel angiodysplastic lesions.

PMID- 8881221
TI  - [Cervical sympathetic paraganglioma].
AB  - A 24-year-old man presented with a long-standing history of Horner's complex and
      a slowly growing cervical mass. Duplex-sonography, angiography, and computed
      tomography revealed a hypervascularized tumor with well defined borders
      displacing the left carotid bifurcation medially. Operative and histological
      findings confirmed the preoperative diagnosis of cervical sympathetic
      paraganglioma.

PMID- 8881222
TI  - [Perspectives in callus distraction].
AB  - Callus distraction is an enrichment of the surgical orthopaedic way of
      reconstructing bone defects, but it is also an effective method of lengthening
      limbs. The biological facts correspond to our knowledge about fracture healing.
      Concerning apparatures, further development is needed. In certain cases the ring
      fixator is the method of choice, but in most indications it is not necessary.
      Every effort should be made to adapt modern technologies, including fully
      implantable systems, to the "biological method" of callus distraction, whenever
      possible.

PMID- 8881223
TI  - [Complex injury of the elbow joint].
AB  - High-velocity trauma now often results in complex injuries to the upper
      extremity, and especially the elbow joint. These can lead to both an enormous
      reduction in the range of motion of the shoulder, elbow and wrist joints, in
      severe cases with complete loss of upper extremity function. A complex injury is
      defined as a fracture and/or dislocation of the elbow in association with (1) a
      serial injury of the upper extremity, (2) a severe soft tissue trauma, or (3)
      concomitant injury to vessels or nerves. Serial fractures, in particular can lead
      to enormous problems with treatment and are often associated with special
      complications. A standardized operative approach therefore seems essential. An
      analysis of our patient populations was made to compare the frequency of
      different injury types, develop specific treatment regimens, and document the
      clinical course. We made a retrospective analysis of patients admitted to our
      facility between 1981 and 1992, with particular reference to cause of accident,
      severity of injury (ISS), type of fracture of the upper extremity (according to
      the AO classification), extent of soft tissue trauma and whether closed or open,
      and the concomitant injuries (vascular, compartment and nerve lesions). Type and
      sequence of therapy and any complications were noted, and the clinical course up
      to consolidation was recorded. The functional result (i.e., ROM, neurology) was
      observed at primary discharge and 12 weeks, 6 months and 2 years later. In the
      time period mentioned 224 complex injuries of the elbow region were noted. Often
      MVAs were the cause of the complex trauma (39% car/30% motorcycle). The average
      injury severity was scored as 32 (ISS) in these, mostly polytraumatized, patients
      (68%). The most frequent fracture combination at the elbow region was combined
      with C2/C3 fractures of the distal humerus (57%) and proximal ulna (43%). A very
      commonly seen complex injury was the Monteggia equivalent, with fracture
      dislocation of the proximal ulna. Most (82%) of the injuries at the elbow region
      were open, and open lesions were similarly frequently seen at the forearm shaft.
      The most frequent concomitant injuries was were to the nerves (63.5%) and the
      plexus. A compartment syndrome developed in 23.8%. This complication was
      frequently seen in multiple trauma patients after primary resuscitation
      (extensive volume therapy) and in serial fractures with more than three
      associated lesions. In 67% of these complex injuries a definitive operation was
      performed as primary treatment (in the first 24 h after injury). Debridement of
      open fractures and fasciotomy in compartment syndrome of the forearm are standard
      techniques in the initial care. In serial fractures all concomitant (humerus,
      forearm, wrist, etc.) fractures were operated on primarily. This primary
      treatment included ORIF of humeral and forearm fractures in 76%. In patients with
      multiple injuries (ISS > 30) primary treatment was not possible in 37%, and in
      these cases transfixation of the elbow joint was performed. Other indications for
      transfixation were severe comminution of the elbow joint, impossibility of
      achieving complete stability after ORIF, extensive soft tissue injuries, with
      healing dependent on short-term immobilization, and finally status following
      extensive ligamentous reconstruction. The most frequent permanent disturbance was
      a persisting nerve lesion in our patients. A significantly reduced range of
      motion (30% deficit flexion/extension) was mostly seen at the elbow (17%), most
      frequently associated with serial fractures (> 3 associated injuries) and with
      severe semicircular soft tissue trauma. The most severe injury in combined trauma
      of the upper extremity is a serial fracture in the elbow region. Such fractures
      are often associated with vascular and nerve lesions. Even with primary fracture
      stabilization and early soft tissue management these often end with significant
      functional deficits.(ABSTRACT TRUNCATED)

PMID- 8881224
TI  - [The significance of hypothermia in polytrauma patients].
AB  - Hypothermia is a frequent event in trauma patients and appears to be related to
      posttraumatic organ dysfunction, although in elective surgery hypothermia is
      known to prevent ischemia reperfusion injury. Retrospectively, we analyzed data
      of 641 trauma patients treated in our institution between 1988 and 1993. At
      hospital admission the core temperature (cT) was > 34 degrees C in the majority
      (64%) of all patients, < 34 degrees C in 23.6% and < 32 degrees C in 12.4%. At 24
      99% had cT of > 34 degrees C. Lethality was twice as high (53%) in patients with
      cT < 32 degrees C as in patients with cT > 34 degrees C (28%). Analysis of
      correlation revealed that hypothermia was paralleled by a longer rescue time,
      greater severity of limb injury, and hypoxia. It also appeared that hypothermia
      is not an independent prognostic factor for posttraumatic lethality. The
      different effects of hypothermia in trauma and elective surgery may be due to a
      lack of energy-storing phosphates such as adenosine triphosphate (ATP). Ongoing
      investigations will identify the role of ATP in trauma-related hypothermia.

PMID- 8881225
TI  - [Plate osteosynthesis management of humerus shaft fractures].
AB  - During the period from 1 May 1990 to 30 November 1994, a total of 62 humeral
      shaft fractures were treated in the Department of Traumatology of the University
      of Bonn. In 42 instances the fracture was internally stabilized primarily, while
      in 13 instances the humeral shaft fractures were treated according to a regimen
      including primary stabilization, usually in an external fixateur, soft tissue
      reconstruction and delayed open reduction and internal fixation using an AO
      plate. The delayed stabilization was carried out 9.1 days, on average, after the
      injury. Seven pseudarthroses were treated electively. The indication for surgery
      was in 28 cases the associated injuries, 18 times the fracture type or form, 7
      times a primary neurological deficit, 7 times a pseudarthrosis and twice the
      underlying systemic disease. A majority of the patients were involved in a motor
      vehicle accident. An open fracture was seen 6 times. Of the 19 primary radial
      palsies, 79% were associated with fractures of the distal diaphysis. The
      complication rate of 11% is comparable to that reported following intramedullary
      stabilization. No infection, pseudarthrosis or long-term radial palsy was
      observed. In three instances, twice following the revision of a pseudarthrosis, a
      temporary radial palsy was noted. All these neurological deficits resolved by the
      6th postoperative day. Bony union was achieved after 16.2 weeks. If the surgeon
      adheres to the proper indications for open reduction and internal fixation, the
      compression plating of the humeral shaft fracture is a viable alternative to
      other forms of stabilization.

PMID- 8881226
TI  - [Quality control after pelvic injuries with a scoring system].
AB  - Quality control after treatment of pelvic injuries is often poor because many
      criteria of assessment lack objectivity. In order to attain improved
      comparability of results, we present a scoring system including subjective as
      well as functional and radiological criteria. The assessment is based on a
      calculation according to the importance of the criteria. The total score supplies
      the final result with a breakdown into excellent, good, fair and poor. 33
      patients with type B and C injuries (Tile) underwent evaluation with this scoring
      system. We found 15 excellent, 10 good, 2 fair and 6 poor results. The score
      showed that patients' most frequent handicap was pain (median 60% of maximum
      score). Hip mobility was hardly affected, and from the radiological point of view
      it appeared that alterations of pelvic symmetry and symphysis were most common.
      Our proposal is to apply this scoring system on a wide basis, because only with a
      great number of patients can the effectiveness of the score be tested and
      different ways of treatment assessed with regard to early and late results. Our
      system could be a useful contribution to sufficient quality control, particularly
      after such complex and severe injuries.

PMID- 8881227
TI  - [Ultrasound imaging of the anterior cruciate ligament. Possibilities and limits].
AB  - We carried out sonography of the femoral origin of the anterior cruciate ligament
      in the dorsal cross section with a 7.5-MHz linear scanner in 25 test subjects
      with healthy knee joints. A physiological difference between the sides in the
      size of the hypoechoic region of the origin could be defined on the basis of the
      measurements obtained in both knee joints. Values outside a reference range which
      could be evaluated from this difference were rated as pathological in terms of an
      anterior cruciate ligament rupture. The reliability of this method in
      definitively diagnosing an anterior cruciate ligament rupture was analysed
      statistically as compared to the golden standard of arthroscopy on 65 patients by
      means of the two-by-two frequency table test. The femoral origin of the cruciate
      ligament in 25 test subjects had a median width of 3.1 mm (range 1.7-5.8 mm) on
      the right and 3.4 mm (range 1.7-4.4 mm) on the left. The median difference
      between the sides is 0.4 mm (range 0-1.8 mm). If the 3rd to the 97th percentile
      is selected as the reference range, our data show a physiological difference
      between the sides of 0-1.5 mm. The median age of the 65 patients was 31 years
      (range 14-74 years). Two thirds of all patients were men. A rupture of the
      anterior cruciate ligament was diagnosed sonographically in 19 patients. The
      result was confirmed arthroscopically in 15 patients. In 4 patients, there was a
      false positive sonographic finding. Forty-six patients did not fulfil the
      sonographic criteria of a rupture of the anterior cruciate ligament. Of these, 38
      showed an intact anterior cruciate ligament on arthroscopy. Eight patients had a
      false-negative sonographic finding. The corresponding statistical analysis showed
      sensitivity of 65%, specificity of 90% and precision of 79%. Accordingly, the
      diagnostic reliability of knee joint sonography in diagnosing a rupture of the
      anterior cruciate ligament appears to be unsatisfactory, since old ruptures,
      above all, cannot be imaged with certainty (sensitivity 65%). On the other hand,
      a positive sonographic finding points with relative certainty to a rupture of the
      anterior cruciate ligament even before the operation (precision 79%).
      Histological analysis of the cruciate ligament preparations obtained
      intraoperatively showed that in particular the fresh anterior cruciate ligament
      rupture can be imaged sonographically. Retrospectively, knowledge of the history
      is thus crucial for interpretation of the sonographic image. After acute trauma
      to the knee, a side difference in the femoral region of origin of the anterior
      cruciate ligament of more than 1.5 mm, as revealed sonographically, is a certain
      indication that the anterior cruciate ligament is ruptured. When there is a
      positive sonographic finding, ligament strain, synovial bleeding and partial
      ruptures of the anterior cruciate ligament as well as plica ruptures must be
      considered as possible diagnoses.

PMID- 8881228
TI  - [Diagnosis of acute rupture of the anterior cruciate ligament. Value of
      ultrasonic in addition to clinical examination].
AB  - Post-traumatic knee injuries often deteriorate if reuptures of anterior cruciate
      ligaments (ACL) are not treated adequately. Further diagnostic procedures are
      required if pain-induced muscle contraction impairs clinical examination. The
      clinical relevance of sonography, however, for the diagnosis of ACL ruptures is
      controversial. Within 25 months, 74 patients were preoperatively evaluated
      clinically and by ultrasound. 58 ruptures of the ACL and 21 lesions of the
      collateral ligaments were confirmed by arthroscopy or arthrotomy. In 16 cases a
      menisceal tear was found, four patients had a luxation of the patella, and two
      had PCL ruptures. The sensitivity of the Lachman test was 93%, of the anterior
      drawer test 68% and of the pivot shift test 48%. Ultrasound diagnosis revealed
      88% of all ACL ruptures (91% if patients with bony ruptures of the ACL were
      excluded). In 75% of ACL ruptures, a popping sensation was reported by the
      patients. In the case of uncertain diagnosis, examination with ultrasound could
      be easily performed before further operative diagnostic procedures are scheduled.

PMID- 8881229
TI  - [Experimental studies of the biomechanics of scaphoid screws].
AB  - The purpose of this study was to determine the anchoring forces of four commonly
      used scaphoid screws in synthetic polyurethane foam. A linear relation was found
      between the length of the probe and the anchoring forces. The leading thread of
      the Herbert screw showed a anchoring force of 54 N/mm, the trailing thread 80
      N/mm, and the Ulrich screw 75 N/mm. This linear relation of the shaft screws was
      only relevant upto a border probe length no longer that of the thread.
      Furthermore, it is valid for screws with continuous threads up to a probe length
      of 12 mm respectively. The cortical screw developed an anchoring force of 59 N/mm
      and the cancellous screw, 63 N/mm. With short probes of 4 and 6 mm, the trailing
      threads of the Herbert and Ulrich screws have the best anchoring forces, with
      values of 319 N/399 N and 307 N/435 N, respectively. The forces necessary for
      extraction of the tested scapoid bone screws placed in 8 mm polyurethane cubes
      were between 404 N and 527 N and were narrowly distributed. An additional
      conclusion of this study was that the application of screws with flat ends
      (Herbert and Ulrich screws) which were placed perpendicular to the dense material
      layer, significantly increased the anchoring forces.

PMID- 8881230
TI  - [Injuries of the talus and calcaneus].

PMID- 8881232
TI  - [Subcapital humerus fracture with lesion of the axillary artery. 2 case reports
      and review of the literature].
AB  - Two cases of fractures of the humeral neck in association with an axillary artery
      injury are reported. Even now, there are still only 14 well-documented cases in
      the literature. Trauma, pattern of injuries and treatment are analyzed. The
      treatment is focused on preservation of hand function, which is more important
      than shoulder motion. Neurovascular damage causes an impairment of hand function.
      The priorities of treatment (reperfusion versus osteosynthesis) are dictated by
      the degree of ischemia. Long-term disability is determined by brachial plexus
      injury.

PMID- 8881231
TI  - An unusual lawn mower injury.
AB  - The authors report a case of foot trauma produced by a piece of the lawn mower
      blade, which was fired projectile-wise from the machine while it was in
      operation. At hit the calcaneous and remained trapped in the bone. The wound
      healed after removal of the foreign body, wound debridement and systemic and
      local antibiotic prophylaxis. In the professional literature available, no report
      has been found on a missile injury produced by a piece of rotating lawn mower
      knife.

PMID- 8881233
TI  - MR of carcinoma-specific monoclonal antibody conjugated to monocrystalline iron
      oxide nanoparticles: the potential for noninvasive diagnosis.
AB  - PURPOSE: To determine if tumor-specific monoclonal antibodies conjugated to
      superparamagnetic monocrystalline iron oxide nanoparticles can be used to yield
      specific diagnoses with the use of MR imaging. METHODS: Monoclonal antibodies
      conjugated to monocrystalline iron oxide nanoparticles were given to nude rats
      with intracranial tumors either by intravenous injection, intraarterial injection
      with osmotic blood-brain barrier disruption, or direct intratumoral inoculation.
      Either L6, a tumor-specific antibody, or P-1.17, a control isotype-matched
      antibody, was used. Coronal T1-weighted, T2-weighted, and spoiled gradient
      recalled acquisition in the steady state images were obtained before, 30 minutes
      after, 6 hours after, and 24 hours after injection. RESULTS: Intravenous
      injection of greater than 2 mg of the tumor-specific antibody showed a specific
      pattern of enhancement of the tumors with the largest concentration of antibody
      in the area with the greatest density of tumor cells. The control antibody showed
      nonspecific changes. After intraarterial injection with barrier disruption to
      increase delivery globally or direct inoculation to increase delivery focally, no
      specific enhancement pattern was seen. CONCLUSION: Monoclonal antibodies
      conjugated with monocrystalline iron oxide particles may provide a method to
      obtain specific diagnoses with the use of MR imaging.

PMID- 8881234
TI  - Dysembryoplastic neuroepithelial tumors: MR and CT evaluation.
AB  - PURPOSE: To evaluate dysembryoplastic neuroepithelial tumors (DNTs) on MR and CT
      studies and to compare DNT with other frequently encountered epileptogenic
      glioneuronal lesions. METHODS: We analyzed the MR images and CT scans of 16
      patients who had complex partial epilepsy and DNT with respect to tumor location,
      size, CT density, MR signal intensity, mass effect, contrast enhancement, and
      heterogeneity, and compared these features with CT and MR findings in 51 cases of
      ganglioglioma and 33 cases of glioneuronal malformation. RESULTS: DNTs were
      located in the temporal lobe in 14 patients and in the frontal lobe in 2
      patients. The cortex was involved in all cases and the subcortical white matter
      in 10 cases. Fifty percent of the tumors had poorly defined contours. On MR
      images, 14 DNTs had multiple cysts and 2 had single cysts. Contrast enhancement
      was observed in 6 DNTs, and mass effect was present in 9. CT scans disclosed
      moderately hypodense lesions in 7 patients and markedly hypodense cystic lesions
      in 6 patients. Two DNTs were calcified. Tumor hemorrhage with perifocal edema was
      observed in 1 case. Contrary to previous reports, slow but definite tumor growth
      was present during a 13-year period in 2 of 6 patients in whom serial CT or MR
      studies were obtained. CONCLUSION: A multicystic appearance on MR images is a
      characteristic feature of DNT and corresponds to its myxoid matrix and
      multinodular architecture. This feature is rare in gangliogliomas and
      glioneuronal malformations, and, as such, may help differentiate DNTs from these
      disorders.

PMID- 8881235
TI  - A proposed model of cerebrospinal fluid circulation: observations with
      radionuclide cisternography.
AB  - PURPOSE: To determine the mechanisms of the tracer distribution at radionuclide
      cisternography (RC). METHODS: Ten patients with venous vasculitis were studied
      with RC. Flow phantom studies were performed mimicking cerebrospinal fluid (CSF)
      circulation with and without a main outlet comparable to the pacchionian
      granulations. RESULTS: Nine of the 10 patients had normal findings on RC images,
      including a maximum uptake over the vertex at 24 hours. In all patients, a second
      maximum occurred in the lumbosacral area. The flow phantom studies showed no
      tracer accumulation at an open outlet corresponding to the pacchionian
      granulations. On the contrary, a maximum arose without such an outlet. A maximum
      always arose at the closed dead ends of the phantom, including the lumbosacral
      area. CONCLUSION: The commonly accepted flow model for CSF circulation needs to
      be revised. The pattern of the normal RC cannot be explained by a bulk flow
      transport of the tracer to an outlet at the pacchionian granulations but rather
      by a primary mixing caused by pulsatile flow with a secondary dilution by newly
      formed CSF from the ventricular system. We suggest that the main absorption of
      the CSF is through the central nervous system to the blood.

PMID- 8881236
TI  - Three-dimensional CT angiography in the detection and characterization of
      intracranial berry aneurysms.
AB  - PURPOSE: To assess the accuracy of three-dimensional CT angiography (CTA) in the
      detection and characterization of intracranial aneurysms and to help determine
      its role as a screening test for aneurysms in the asymptomatic population and as
      an adjunct to angiography in subarachnoid hemorrhages and in the follow-up of
      untreated aneurysms. METHODS: In a blinded, prospective study, the 3-D CTA
      studies in 80 patients with symptomatic aneurysms were analyzed for the presence
      and morphology of aneurysms. Angiography or surgery acted as the control.
      RESULTS: Ninety-four aneurysms were found in 63 patients. Negative findings at
      angiography were noted in 17. Sensitivity and specificity of 3-D CTA for all
      aneurysms, all patients, and aneurysms 5 mm or smaller were 90.4% and 50%, 98.4%
      and 82.4%, and 78.8% and 51.9%, respectively. CONCLUSION: Three-dimensional CTA
      may have a role in noninvasive screening for asymptomatic aneurysms in the
      general population, but caution is advocated when data obtained from symptomatic
      patients are extrapolated to the asymptomatic population who harbor smaller
      aneurysms. Also, 3-D CTA may be useful as an adjunct to angiography in the
      characterization of berry aneurysms and in the follow-up of untreated aneurysms.

PMID- 8881237
TI  - Cerebral aneurysms: evaluation with three-dimensional CT angiography.
AB  - PURPOSE: To evaluate the usefulness of three-dimensional CT angiography (CTA), in
      which contrast material is used to create reformations of dynamic scans, in the
      diagnosis and the preoperative evaluation of cerebral aneurysms. METHODS: We used
      3-D CTA to examine 65 patients with suspected or angiographically verified
      cerebral aneurysms. A blind study was performed to evaluate the diagnostic
      accuracy of 3-D CTA for cerebral aneurysms with the use of conventional
      angiography as the reference standard. RESULTS: In 50 patients, conventional
      angiography revealed 73 cerebral aneurysms ranging from 2 to 32 mm in maximum
      diameter. Three of the 73 cerebral aneurysms were located outside the imaging
      volume of 3-D CTA. The sensitivities of the two neuroradiologists for the
      remaining 70 aneurysms were 67% and 70%, respectively. Although 3-D CTA depicted
      cerebral aneurysms 5 mm or larger with good accuracy, it was less useful for the
      detection of smaller aneurysms. For the evaluation of giant aneurysms, this
      technique elucidated the relationships among the aneurysm, surrounding arteries,
      and neighboring bone structure. CONCLUSION: Three-dimensional CTA is useful for
      the diagnosis of cerebral aneurysms with diameters of 5 mm or more. This
      technique is especially useful in the preoperative evaluation of giant aneurysms.

PMID- 8881238
TI  - CT angiography in the examination of patients with aneurysm clips.
AB  - The use of CT angiography is described in three patients for the evaluation of
      intracranial clips after surgery for an aneurysm. A postprocessing technique is
      described in which shaded-surface-display models were superimposed on maximum
      intensity projection CT angiograms. CT angiograms showed residual aneurysmal
      filling adjacent to a clip, patency of a vessel thought to be compromised by
      recent clip placement, and errant position of a clip, which required repeat
      surgery.

PMID- 8881239
TI  - Aqueduct compression from venous angioma: MR findings.
AB  - Vascular compression as the cause of aqueductal stenosis is rare. In a 16-year
      old girl with hydrocephalus, MR imaging provided evidence of aqueductal stenosis
      caused by a venous angioma in the tectum and midbrain. This indicates the
      usefulness of MR imaging for the evaluation of obstructive hydrocephalus.

PMID- 8881240
TI  - Hemangiomas of the head, neck, and chest with associated vascular and brain
      anomalies: a complex neurocutaneous syndrome.
AB  - PURPOSE: To describe the vascular and nonvascular intracranial and extracranial
      anomalies associated with hemangiomas and vascular malformations of the face,
      neck, and/or chest. METHODS: Seventeen patients had a physical examination and
      imaging studies consisting of one or more of the following:
      pneumoencephalography, conventional carotid and vertebral arteriography, CT, MR
      imaging, and MR angiography. RESULTS: Conventional arteriography revealed
      persistence of the trigeminal artery in 5 cases, absence of internal or external
      carotid and/or vertebral arteries in 11 cases, persistence of intervertebral
      arteries in 1 case, deformities of the aortic arch in 3 cases, and anomalies of
      the intracranial arteries in 3 cases. MR angiography revealed persistence of the
      trigeminal artery in 1 case in which conventional arteriography failed to show
      the malformation, and permitted visualization of narrowing of the intracranial
      arteries. CT and MR imaging showed a cerebellar anomaly in 8 cases and cerebral
      cortical dysplasia with cerebral hemispheric hypoplasia in 1 case. Vascular and
      nonvascular anomalies appeared ipsilateral to the external vascular abnormalities
      in most cases. CONCLUSION: This study demonstrates the association of cutaneous
      angiomas with anomalies affecting intracranial and extracranial arteries, the
      cerebellum, and, less frequently, the cerebral hemispheres and aortic arch. This
      association constitutes a relatively frequent neurocutaneous disorder, which we
      call the cutaneous hemangioma-vascular complex syndrome.

PMID- 8881241
TI  - Use of functional MR to map language in multilingual volunteers.
AB  - PURPOSE: To use functional MR imaging to compare brain activation during
      processing of languages in which multilingual volunteers are fluent with brain
      activation during processing of languages in which they are not fluent. METHODS:
      Echoplanar images were obtained for five right-handed male multilingual subjects
      who performed a language task in three languages, one of which was a language in
      which the subject was not fluent. The functional MR technique included echoplanar
      images obtained at 1 per second during cycles of rest and performance of the
      task, from which functional images were processed by means of cross-correlation
      analysis. The numbers of active pixels in each volunteer and for each language
      were compared. RESULTS: Activation was noted in the left frontal lobe in all
      subjects performing language tasks. In each subject, the number of activated
      pixels was greatest for the language in which the subject was least fluent.
      CONCLUSION: Functional MR imaging shows differences in the processing of
      different languages in multilingual volunteer subjects, depending on the level of
      fluency in the language, and it is an effective functional imaging method for
      studying the processing of different languages.

PMID- 8881242
TI  - Regional cerebral blood flow response in gray matter heterotopia during finger
      tapping: an activation study with positron emission tomography.
AB  - We examined regional cerebral blood flow response in a patient with gray matter
      heterotopia located beneath the sensorimotor cortex during a finger tapping task.
      We found regional cerebral blood flow was specifically increased during
      contralateral finger tapping. This indicated the possibility of functional
      differentiation of the ectopic neurons despite incomplete migration.

PMID- 8881243
TI  - MR angiography of normal intradural vessels of the thoracolumbar spine.
AB  - PURPOSE: To identify and describe the normal intradural vessels detected on MR
      angiograms of the thoracolumbar spine. METHODS: Six adult subjects who had
      clinical evidence of myelopathy, yet normal findings at spinal digital
      subtraction angiography (DSA), were also studied without and with contrast
      enhanced MR imaging and three-dimensional time-of-flight, single-slab MR
      angiography. Sagittal and coronal subvolume (targeted) maximum intensity
      projection images were compared with arterial and venous phase DSA images.
      Angiographic images were then compared with postmortem, formalin-fixed cord
      specimens. RESULTS: Recognizable intradural vessels were detected only on
      contrast-enhanced MR angiograms. These vessels corresponded to the posterior
      and/or anterior median (midline) veins and the great medullary veins. The median
      veins had variable but mild tortuosity. The medullary veins, which extended from
      the median veins and coronal venous plexus on the cord surface to the epidural
      venous plexus, were relatively straight and usually located at T-12 or L-1. The
      anterior spinal artery could partially contribute to the anterior midline
      vascular signal. CONCLUSION: The intradural vessels identified on contrast
      enhanced MR angiograms are primarily veins, and these are usually the largest
      vessels on or near the cord surface. The limited number and minimal tortuosity of
      these veins may serve as a baseline for the examination of patients with
      clinically suspected arteriovenous malformation or fistula.

PMID- 8881244
TI  - Postoperative cerebrospinal fluid leaks of the lumbosacral spine: management with
      percutaneous fibrin glue.
AB  - PURPOSE: To assess CT-guided injection of fibrin glue for the management of
      lumbosacral cerebrospinal fluid (CSF) leaks. METHODS: Six consecutive patients
      with postoperative CSF leaks were treated after CSF aspiration under CT guidance.
      A solution of cryoprecipitate was simultaneously injected with a 10% calcium
      chloride solution containing 2000 units of thrombin per milliliter. In one
      patient, 0.5 mL of iopamidol was added to the calcium chloride/thrombin mixture
      before injection. Placement of the fibrin glue aggregate was confirmed by CT
      imaging. To determine outcomes we reviewed the patients' records, postprocedure
      imaging studies, and physical findings, and we interviewed the patients directly.
      RESULTS: In three patients with postoperative CSF leaks, symptoms resolved after
      treatment. Despite imaging evidence of successful plug deployment, two other
      patients still had severe symptoms, and they underwent surgery after 2 and 18
      hours, respectively. One patient had a continued CSF leak and a headache after 12
      hours; follow-up surgery repaired an unsuspected dural tear just distal to the
      site of original surgery underneath the lamina and not covered by the fibrin
      glue. After one of the successful procedures, the patient had a fever and a
      headache, probably because of aseptic meningitis, which resolved after 2 days.
      CONCLUSION: Percutaneous CT-guided placement of fibrin glue may provide
      nonsurgical treatment for postoperative CSF leaks, potentially avoiding a major
      and technically difficult surgical procedure.

PMID- 8881245
TI  - Ionic versus nonionic paramagnetic contrast media in differentiating between scar
      and herniated disk.
AB  - PURPOSE: To compare the MR contrast enhancement produced by ionic and nonionic
      paramagnetic contrast media in herniated disk fragments with that in epidural
      scar tissue. METHODS: A recurrent herniated disk was modeled in canines by using
      laminectomy to place a fragment of disk cartilage in the epidural space. The dogs
      were studied 88 and 90 days after laminectomy with MR imaging enhanced with an
      ionic or a nonionic paramagnetic contrast medium. Contrast enhancement of the
      epidural scar tissue and the epidural disk fragment was measured at 2, 22, and 45
      minutes after the injection. RESULTS: Contrast enhancement was consistently and
      significantly higher in scar tissue than in disk fragments, although the
      difference decreased between 2 and 45 minutes after administration of contrast
      medium. Enhancement of disk fragments was less with the ionic than with the
      nonionic contrast medium. Contrast between the disk fragments and scar was also
      greater with the ionic than with the nonionic medium. CONCLUSIONS: The contrast
      between recurrent disk fragments and scar tissue is affected by the timing of the
      scan and the choice of contrast medium. Scans obtained immediately after the
      injection of contrast medium show more contrast between disk fragment and scar
      than do delayed scans. Recurrent herniated disk fragments are more effectively
      shown by ionic than by nonionic media.

PMID- 8881246
TI  - The forgotten condyle: the appearance, morphology, and classification of
      occipital condyle fractures.
AB  - PURPOSE: To evaluate the appearance, morphology, and treatment of occipital
      condyle fractures (OCF). METHODS: Cases were collected by a retrospective and
      prospective analysis of teaching files and case logs. Patients' charts, when
      available, were reviewed for age, sex, mode of injury, physical examination,
      Glascow Coma Scale score, and associated injuries. Plain films and CT images were
      reviewed to determine OCF type and to assess for the presence of associated
      cervical spine and/or intracranial trauma. RESULTS: Fifteen patients with OCF, 13
      occurring in a 43-month period, were identified. Ten patients were involved in
      motor vehicle accidents. Severity of closed head injury and associated clinical
      findings were variable. Three patients had associated cervical spine fracture.
      According to the Anderson and Montesano classification, two patients (13%) had
      type I OCF, eight patients (54%) had type II OCF, and five (33%) had type III
      OCF. Fourteen of the fractures were identified on screening trauma head CT scans.
      Treatment varied according to the presence of associated injuries and stability
      of the cervical spine. CONCLUSIONS: Although OCFs are rare, they will be
      encountered by most radiologists who see a significant amount of trauma. Type II
      OCFs were the most common fracture type in our series. Type III fractures were
      the second most common and potentially unstable. CT should be initiated at the
      level of the C-1 ring to screen for the presence of OCF in all patients who have
      suffered trauma.

PMID- 8881247
TI  - Fibrosing inflammatory pseudotumors involving the skull base: MR and CT
      manifestations with histopathologic comparison.
AB  - PURPOSE: To describe the MR and CT features of fibrosing inflammatory
      pseudotumors of the skull base region, and to document the MR signal intensity of
      the lesions with histopathologic comparison. METHODS: We reviewed the MR and CT
      studies of five patients with pathologically proved fibrosing inflammatory
      pseudotumor involving the skull base. Unenhanced spin-echo T1- and T2-weighted
      and contrast-enhanced T1-weighted MR images were obtained at 0.5 T in three
      patients and at 1.5 T in two patients. MR findings were correlated with
      histopathologic findings in all five cases, and the enhancement pattern was
      compared with CT findings in three cases. RESULTS: In three cases, the cavernous
      sinus was involved unilaterally, with adjacent extracranial infiltrative masses.
      In one case, both orbits, the cavernous sinuses, and the tentorium were involved
      with diffuse infiltrative lesions. One patient had an infiltrative nasopharyngeal
      mass; and in all five patients, MR images showed localized involvement of the
      skull base, with bone marrow replaced by tumor. The soft-tissue lesions were
      hypointense on T2-weighted images in all five cases and showed homogeneous
      contrast enhancement. Histopathologic studies revealed scanty inflammatory cell
      infiltration with densely fibrotic background in all cases. The hypointensity of
      the lesions on T2-weighted images seemed to be related to the degree of fibrosis.
      CONCLUSION: Fibrosing inflammatory pseudotumor shows characteristic MR findings
      of infiltrative lesion with bone destruction and hypointensity on T2-weighted
      images. The lack of mobile protons due to the fibrotic background and/or high
      cellularity of the lesions may be the reason for their hypointensity and weaker
      enhancement on MR images.

PMID- 8881248
TI  - Juvenile fibromatosis of the posterior mediastinum with intraspinal extension.
AB  - Chest radiography, CT, and MR imaging were performed in a 3-year-old girl who had
      posterior mediastinal fibromatosis with transforaminal intraspinal and chest wall
      extension. Chest radiographs and CT scans showed a slow-growing, noncalcified but
      locally aggressive left paravertebral mass. The mass was slightly hyperintense
      relative to muscle on both T1-weighted and fast spin-echo T2-weighted MR images.

PMID- 8881250
TI  - Trisacryl gelatin microspheres for therapeutic embolization, I: development and
      in vitro evaluation.
AB  - PURPOSE: To develop a precisely calibrated, perfectly spherical, stainable, soft,
      and implantable but nonresorbable particulate embolization material. METHODS:
      Calibrated particles with a trisacryl gelatin polymer core and hydrophilic
      surface characteristics were obtained by reversed emulsion synthesis followed by
      application of a wet-sieving technique. Particles were suspended in saline,
      bottled, and sterilized. Quality control included analysis of particle diameters
      before and after sieving and of suspension sterility and apyrogenicity. Particles
      were subsequently tested to ascertain their compatibility with commercially
      available microcatheters. RESULTS: The resulting embolization material consisted
      of spherical, stainable microspheres of medical grade with diameters ranging from
      130 microns to 1200 microns. Sieving the suspension produced particle groups of
      homogeneous size (accuracy, +/- 20-100 microns). At injection, the particles
      showed no tendency to build aggregates or to obstruct the microcatheters.
      CONCLUSION: Precisely calibrated and easy-to-use microspheres were obtained that
      satisfied the biomedical requirements for implantation as an embolization
      material.

PMID- 8881249
TI  - Preoperative endovascular embolization of craniospinal hemangioblastomas.
AB  - PURPOSE: To determine whether hemangioblastomas, highly vascular tumors requiring
      surgery that is potentially complicated by excessive bleeding, can be embolized
      safely by using interventional techniques that furnish a more avascular surgical
      field. METHODS: Nine hemangioblastomas involving either the cerebellum or the
      spinal cord were embolized preoperatively. In each case the feeding artery was
      selectively catheterized with a microcatheter and the hypervascular tumor nidus
      was devascularized with polyvinyl alcohol particles. RESULTS: Two patients who
      had undergone recent attempts as surgical resection at another institution had
      repeat surgery after endovascular embolization rendered the tumor nidus
      avascular. At surgery, the tumor was completely removed in one case and markedly
      debulked in the other. In all nine cases, blood loss after embolization was
      reported to be less than expected by experienced surgeons. In addition,
      manipulation and removal of the tumor was reported to be subjectively easier in
      these embolized tumors. The embolization procedure caused no permanent
      complications; however, one patient with a posterior fossa hemangioblastoma and
      hydrocephalus worsened clinically within 12 hours of embolization. This event was
      thought to be caused by obstructive hydrocephalus resulting from tumor swelling.
      Emergency craniotomy, ventricular decompression, and surgical resection of the
      tumor produced complete resolution of the signs and symptoms. CONCLUSIONS: Our
      results indicate that preoperative embolization of hemangioblastomas is a safe
      procedure that is useful in aiding surgical resection of these highly vascular
      tumors.

PMID- 8881252
TI  - The usefulness of MR in establishing the diagnosis of parotid pleomorphic
      adenoma.
AB  - PURPOSE: To assess the usefulness of MR findings in establishing a specific
      diagnosis of parotid pleomorphic adenoma. METHODS: T1-weighted and T2-weighted MR
      images with and without contrast enhancement were obtained in 82 patients with
      parotid tumors. Imaging findings in the 38 patients in whom surgery subsequently
      revealed pleomorphic adenomas were compared with findings in the 44 patients who
      had other types of tumor. Specifically, the homogeneity, signal intensity,
      contrast enhancement, capsule thickness, lobulation, adenopathy, and infiltration
      of adjacent fat were compared among the different types of tumor. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value were calculated. RESULTS: A low-signal capsule on T2-weighted images and a
      lobulated contour characterized most pleomorphic adenomas. The sensitivity of the
      first finding for pleomorphic adenoma was 82%; specificity, 85%; positive
      predictive value, 82%; and negative predictive value, 84%. For the second
      finding, the sensitivity was 53%; specificity, 84%; positive predictive value,
      74%; and negative predictive value, 67%. CONCLUSION: None of the signs evaluated
      had perfect sensitivity and specificity. The MR findings of a complete capsule,
      lobulated contour, or high T2 signal intensity have a high predictive value for
      the diagnosis of pleomorphic adenoma.

PMID- 8881251
TI  - Trisacryl gelatin microspheres for therapeutic embolization, II: preliminary
      clinical evaluation in tumors and arteriovenous malformations.
AB  - PURPOSE: To evaluate an embolic agent that is precisely calibrated, perfectly
      spherical in shape, and soft but nonresorbable for use in the embolization of
      vascular disease of the head, neck, and spine in humans. METHODS: We used supple,
      hydrophilic, and calibrated trisacryl gelatin microspheres 200, 400, 600, 800 and
      1000 microns in diameter for superselective embolization in 105 patients (27
      tumors, 14 facial arteriovenous malformations [AVMs], 37 spinal cord AVMs, 21
      cerebral AVMs, and 6 miscellaneous diseases). We used particles in 200 to 600
      microns in diameter for tumors and for facial AVMs, particles 400 to 600 microns
      in diameter for spinal cord AVMs, and particles over 1000 micros in diameter for
      cerebral AVMs. RESULTS: Delivery of the embolic material was easy: microspheres
      did not aggregate and catheters did not become obstructed by particles. It was
      possible to control the embolization through precise accounting of the amount of
      microspheres and matching of the particle size to the size of the pathologic
      vascular network. CONCLUSION: The microspheres are easy to use and allow precise
      control of the embolization procedure. Their physical characteristics make them a
      safe embolic agent.

PMID- 8881253
TI  - Epithelial-myoepithelial carcinoma of the parotid gland.
AB  - We describe an unusual salivary neoplasm, an epithelial-myoepithelial carcinoma
      (EMEC) of the parotid gland, that occurred in a 64-year-old man. A CT scan showed
      a fairly well defined heterogeneous lesion with smooth margins and slight
      enhancement. MR images showed a lesion with intermediate T1-weighted signal
      intensity and a relatively high T2-weighted signal intensity. Although the
      imaging characteristics of EMEC on both CT and MR studies are nonspecific,
      clinicians and radiologists must be aware of its high local recurrence rate,
      which has been reported to approach 50% in some series, and thus the need for
      periodic postoperative imaging to detect early recurrence.

PMID- 8881254
TI  - MR evaluation of epiglottic disruption.
AB  - Epiglottic disruption is an uncommon injury usually associated with significant
      supraglottic trauma. This injury may be overlooked because of the difficulty in
      examining the larynx or other associated severe injuries. We present two cases of
      clinically unsuspected epiglottic disruption that were first seen on MR images of
      the neck.

PMID- 8881255
TI  - Nodular fasciitis as a vascular neck mass.
AB  - Nodular fasciitis falls within the benign spectrum of fibrous soft-tissue tumors.
      We present a case of nodular fasciitis in the supraclavicular fossa in which an
      unusual angiographic presence of neovascularity is shown.

PMID- 8881256
TI  - Multiple myeloma involving the thyroid cartilage.
AB  - Extraosseous multiple myeloma involving the larynx is rare. We describe a patient
      with multiple myeloma and a plasmacytoma involving the thyroid cartilage.
      Ossification of the thyroid cartilage with formation of a marrow space could
      explain the occurrence of multiple myeloma in this unusual location.

PMID- 8881257
TI  - MR of cerebral abnormalities concomitant with primary intracerebral hematomas.
AB  - PURPOSE: To determine whether arteriolar vessel wall degeneration in primary
      intracerebral hematomas might be associated with ischemic brain lesions and
      clinically silent (apparently intracerebral) previous hemorrhages. METHODS: The
      MR images of 120 consecutive patients (mean age, 60 years; age range, 22 to 84
      years) with their first stroke caused by a primary intracerebral hematoma were
      reviewed retrospectively for coexisting ischemic damage and previous bleeds.
      RESULTS: Early confluent to confluent white matter hyperintensities, lacunes, or
      infarction were present in 83 (69%) of the patients, and 39 (33%) had had
      previous hemorrhages consisting of microbleeds or old hematomas. Extensive white
      matter hyperintensities and lacunes were most frequent in patients with thalamic
      primary intracerebral hematomas. There was no relationship between the frequency
      of old hemorrhages and the location of subsequent primary intracerebral
      hematomas. CONCLUSION: Clinically silent ischemic lesions and previous
      hemorrhages are a common finding on MR images of patients with primary
      intracerebral hematoma. They may therefore serve as evidence of diffuse
      microangiopathy with a possible increased risk for cerebral hemorrhage.

PMID- 8881258
TI  - Multiplanar MR and anatomic study of the mandibular canal.
AB  - PURPOSE: To evaluate the MR appearance of the mandibular canal and its contents.
      METHODS: Cadaveric mandibles were imaged at 1.5 T and 3 T, then sectioned with a
      cryomicrotome. The size, shape, signal intensity, and pattern of structures in
      the mandibular canal were identified on MR images by comparing them with
      corresponding anatomic sections. RESULTS: The inferior alveolar nerve and
      connective tissue were identified on the 1.5-T and 3-T images in the mandibular
      canal. Within the nerve the axon bundles were distinguished from the nerve sheath
      on the 3-T images. CONCLUSION: This study suggests that MR images can show
      excellent anatomic detail in the mandibular canal.

PMID- 8881259
TI  - MR of nasolabial cysts.
AB  - We report the MR imaging findings in two cases of nasolabial cysts. Demonstration
      of their extraosseous location with cross-sectional imaging should prevent
      confusion with maxillary cysts and obviate unwarranted dental or maxillary
      surgery.

PMID- 8881260
TI  - Pseudallescheria boydii infection of the brain: imaging with pathologic
      confirmation.
AB  - Pseudallescheria boydii is a rare opportunistic microorganism that usually
      infects immunosuppressed hosts. In this patient with cerebral infection by P
      boydii, imaging findings included enhancement of the ependyma of a lateral
      ventricle and of the caudate nucleus.

PMID- 8881261
TI  - MR findings in listerial rhombencephalitis.
AB  - We describe a case of listerial rhombencephalitis in a previously healthy 40-year
      old man. The diagnosis was based on the clinical findings, results of
      cerebrospinal fluid analysis, blood culture, and MR imaging findings. The
      treatment was started before culture results were available, and the patient had
      a full clinical recovery.

PMID- 8881262
TI  - Progressive multifocal leukoencephalopathy: clinical and MR response to
      treatment.
AB  - Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease
      that occurs in immunocompromised hosts. We describe two patients with biopsy
      proved PML who showed improvement clinically and radiologically after medical
      therapy. These cases reveal that interval improvement can in rare instances be
      consistent with a diagnosis of PML.

PMID- 8881263
TI  - Annotated bibliography.

PMID- 8881264
TI  - [Gene therapy of neurological diseases].
AB  - In hereditary neurological diseases, gene transfer into neurons is made difficult
      by: the nature of the cells (postmitotic cells, that cannot be cultured,
      genetically modified ex vivo, then retransplanted), sometimes, their widespread
      localization, the blood-brain barrier. However, three viral vectors derived from
      adenovirus, Herpes simplex virus and adeno-associated virus have been shown to be
      very efficient in transferring DNA into brain cells. All of these vectors can
      infect resting cells, especially neurons, and are efficient in vivo. Retroviral
      vectors which can infect dividing cells only are mainly used for ex vivo genetic
      modification of cells (neural progenitor cells, myoblasts, fibroblasts) followed
      by intracerebral transplantation. Alternatively, genetically modified cells can
      be transplanted in a peripheral site if the transgene product is able to cross
      the blood-brain barrier or to be transported retrogradely from the nerve
      terminals. We have especially investigated the potential interest of adenoviral
      vectors to transfer foreign genes into brain cells and to treat animal models of
      neurological diseases. These vectors allowed us to transfer the lacZ gene into
      any neural cell type, including neurons, glia, photoreceptors and olfactory
      receptors, ex vivo, in cell culture, and in vivo, by stereotactic administration.
      In addition, axonal transport of adenoviral vectors has been demonstrated, e.g.
      in the substantia nigra after injection into the striatum, in the olfactory bulb
      after intranasal instillation and in spinal motor neurons after intramuscular
      injection. After intracerebroventricular injection, ependymal cells are massively
      infected and express the transgene for several months, as this is also observed
      in neurons. Through the spinal canal and cerebrospinal fluid, the vector can
      diffuse to a considerable distance from the injection point, e.g. to the lumbar
      spinal cord after injection in the suboccipital region. To test the biological
      function of transgenes transferred through adenoviral vectors, we have
      constructed vectors with cDNAs or genes for various neutrophic factors: CNTF,
      NT3, BDNF and GDNF. These vectors were biologically active on target cells, ex
      vivo and in vivo. In the pmn mouse model of progressive motor neuronal
      degeneration, some of these vectors, alone or combined, allowed for prolongation
      of life of homozygous animals by more than two fold, and for decrease in the
      demyelination of phrenic nerve axons. Finally, we have also constructed an
      adenoviral vector carrying the alpha-hexosaminidase cDNA, encoding the enzyme
      subunit deficient in Tay Sachs patients. This vector permitted to normalize
      ganglioside metabolism in Tay Sachs fibroblasts and is currently tested in knock
      out mice deficient in hexosaminidase A. In spite of all these encouraging
      results, we are nevertheless aware that progress in vector design and delivery
      strategies will be needed before gene therapy can become a realistic
      therapeutical strategy in humans.

PMID- 8881265
TI  - [Development of adenoviral vectors in gene therapy: application to gene transfer
      in muscles].
AB  - This review focuses on the general properties of adenovirus vectors and their
      application to muscle gene transfer. In the prospect of a treatment for Duchenne
      muscular dystrophy, in vivo expression of the dystrophin gene in animal models
      remains the main concern. After the presentation of the two partners: adenovirus
      and muscle, we summarize our results of gene transfer in mice. We have evaluated
      efficiency of systemic and intramuscular injections, the impact of age at
      injection, the duration of expression in adult normal and genetically
      immunosuppressed SCID mice, using a recombinant adenovirus expressing a reporter
      gene. After adenovirus-mediated transfer of a mini-model, we have shown an
      efficient and stable expression of the transgene, a long-term correction of the
      degeneration process and a functional protection of the treated muscle. The
      discussion focuses on the problems and the perspectives for gene therapy: safety
      problems, improvement of safety and vector capacity, host immune response,
      delivery to muscle and muscle-targeted expression.

PMID- 8881266
TI  - [Gene transfer with amino lipids and amino polymers].
AB  - Several non-permanent polycations possessing substantial buffering capacity below
      physiological pH, such as lipopolyamines and polyethylenimines, are efficient
      transfection agents per se, i.e. without the addition of lysosomotropic bases, or
      cell targeting or membrane disruption agents. These vectors have been shown to
      deliver genes as well as oligonucleotides both in vitro and in vivo. Our
      hypothesis is that their efficiency relies on extensive endosome swelling and
      rupture that provides an escape mechanism for the polycation/DNA particles.

PMID- 8881267
TI  - [Selective transfection of animal cells by non viral vectors: polylysine carrying
      recognition signals].
AB  - A process for the selective transfer of genes using glycosylated polylysine was
      established. Glycosylated polylysines and plasmid DNA form complexes which are
      taken up by cells expressing surface lectins recognizing the sugar moieties of
      glycosylated polylysines. Modifications made to this process allow for efficient
      and specific transfer in in vitro animal cell models.

PMID- 8881268
TI  - [Gene therapy in lysosomal diseases].
AB  - The study of the mechanisms of secretion and recapture of lysosomal enzymes has
      lead to the proposal of a treatment of lysosomal diseases by enzyme replacement.
      Autologous implants of genetically modified cells which secrete enzymes ensure
      systemic distribution of the lacking enzyme. A procedure which permits
      reimplantation of genetically modified fibroblasts is described. The stable
      secretion of human glucuronidase by autologous fibroblasts was thus obtained in
      animal species. This approach should by applicable to the treatment of Hurler's
      syndrome by obtaining the production and distribution of alpha-L-iduronidase in
      patients lacking this enzyme by retroviral transfer of the human alpha-L
      iduronidase gene to cultured fibroblasts and by preparation of implants.

PMID- 8881270
TI  - [Gene transfer in human hematopoietic stem cells isolated from peripheral blood].
AB  - To insert a new genetic information by gene transfer into haemopoietic stem cells
      would result in expression of the transgene in progenitors and progeny of cell
      blood lineages. If successfull, such an approach would open interesting
      prospectives in the field of experimental research and in the possibility to
      treat genetic defects affecting blood lineages such as immune deficiencies (ADA,
      SCID, AIDS) or enzymes defects. Moreover progenitors could be engineered to
      become more resistant to chemotherapy or oncogenic process. Many parameters and
      technical problems are still involved in this issue, including identification,
      isolation and selection of the most primitive progenitors, and search for the
      most efficient vectors to insert new genes into the target cells. So far
      retroviral vectors have been shown to be the most effective but search for better
      vectors are still underway. Peripheral blood stem cells isolated from patients
      stimulated by cytokines and/or chemotherapy appear interesting target cells for
      genetic manipulations aimed to correct an acquired or genetic defect.

PMID- 8881269
TI  - [Towards gene therapy in familial hypercholesterolemia].
AB  - Familial hypercholesterolemia (FH) is an inherited disease caused by a defect in
      the gene encoding the Low Density Lipoprotein receptor (LDL-R). The ex vivo
      hepatic gene therapy which restore the expression of the normal protein in
      hepatocytes should correct the disease. Improved transduction efficiency and long
      lasting expression of the transduced gene remain the main goals of gene therapy
      research. We developed an efficient and reliable method for in vivo transduction
      of human, mouse and primate primary hepatocytes. A retroviral vector bearing the
      LDL-R cDNA driven by the liver-type pyruvate kinase promoter allows high and
      tissue specific expression of the gene in primary hepatocytes. A second vector
      with a housekeeping promoter corrects the LDL-R deficiency in fibroblasts from a
      FH patient. Ex vivo preclinical studies in non-human primates will provide new
      insight in transduced cells biology after reimplantation.

PMID- 8881271
TI  - [Gene therapy for hereditary immunodeficiencies].
AB  - There are numerous inherited immunodeficiencies characterized by either defects
      in T, B lymphocytes, phagocytic cells or the complement system. About 20 genes
      involved in inherited immunodeficiencies have now been identified. This opens
      theorically the possibility to consider gene therapy for the most severe of the
      diseases. A logical approach consists in attempting gene transfer into
      hematopoietic stem cells in order to achieve a definitive cure. However, the
      presently available vectors, i.e. retroviruses induce only stable gene
      integration and possibly expression into cycling cells while most stem cells are
      in G0/G1. This precludes at this time efficient gene therapy for many inherited
      immunodeficiencies. Nevertheless in instances, where there is an early block in
      cell differentiation like in adenosine desaminase deficiency (ADA) or X-L severe
      combined immunodeficiency (IL2 R gamma deficiencies), a selective advantage could
      be provided to the few transduced stem cells enabling progressive lymphocyte
      differentiation. This hypothesis sets the basis for the ongoing clinical studies
      in patients with ADA deficiency and will be assessed in available animal model of
      XL SCID.

PMID- 8881272
TI  - [Gene therapy in cystic fibrosis: molecular and cellular aspects].
AB  - Gene therapy has become a potential treatment for Cystic Fibrosis (CF) when the
      CFTR gene responsible for the disease was isolated in 1989. As premature death is
      still the norm, the demand is now for a dramatically improved therapy. The
      pulmonary manifestations of CF being life-limiting, many gene therapy studies
      have focused on gene transfer via various vectors into airway epithelial cells,
      namely in murine models of CF. These preclinical studies led to the first
      clinical trials, which showed that many hurdles still do exist and that more
      efficient vector systems need to be developed. Both a remarkable scientific
      effort and a close collaboration between scientists and clinicians are highly
      necessary in order to move from the present stage of "cautious optimism" toward
      the ultimate goal: a cure for CF.

PMID- 8881274
TI  - [Reglementation, organization and development of clinical researches in gene and
      cellular therapy].
AB  - Examination of legislative and reglementary framework where genic and cellular
      therapy take place: in a French and US context. Actual evolution. Comparison of
      difficulties in development and valorisation of project treatments in France and
      the US.

PMID- 8881273
TI  - [Aerosol administration of a replication defective recombinant adenovirus
      expressing normal human cDNA-CFTR in the respiratory tractus in patients with
      cystic fibrosis].
AB  - At present it is conceivable to think that gene therapy represents a way to treat
      or even prevent the respiratory manifestations of cystic fibrosis. Consistent to
      such a concept, there is sufficient evidence that Ad-CFTR, a recombinant
      replication-deficient adenovirus expressing the human cystic fibrosis
      transmembrane conductance regulator cDNA, can vectorize the expression of a
      functional CFTR (cystic fibrosis transmembrane conductance regulator) to the
      nasal and airway epithelia. The clinical protocol was designed to assess the
      safety of single escalating doses of a replication defective adenovirus
      expressing the cystic fibrosis transmembrane conductance regulator gene (Ad-CFTR)
      when administered to the tracheobronchial portion of the airways and whether
      biological efficacy of CFTR delivery could be demonstrated. Six cystic fibrosis
      patients received nasal instillation and subsequent aerosol (Optineb, Air
      Liquide, Paris, France) administration of Ad-CFTR the following day. Doses (pfu)
      applied to the nose were 10(5) (patients SG and PB), 10(7) (patients FP and EP)
      and 4 x 10(8) (patients DS and FG), while aerosolised doses were 10(7) (patients
      SG and PB), 10(8) (patients FP and EP) and 5.4 x 10(8) (patients DS and FG),
      respectively. No acute toxic effects, no increase in the titer of anti-adenovirus
      antibodies and no spreading or shedding of Ad-CFTR were detected. In one patient
      Ad-CFTR DNA was found in the urine and blood two days after aerosolisation. Ad
      CFTR DNA was detected in nasal and bronchial brush samples, in BAL, in saliva and
      tonsils 21, 8, 14 and 4 days post virus administration, respectively. Ad-CFTR
      mRNA (RT-PCR on bronchial cells) and CFTR protein (immunochemistry on nasal and
      bronchial cells) were detected up to 14 days following Ad-CFTR administration.
      These results show that the nebulisation of Ad-CFTR is a possible approach for
      treating the respiratory manifestation of cystic fibrosis.

PMID- 8881275
TI  - [SLTR, a new family of retroviral vectors for gene transduction].
AB  - In this article, we describe two novel methods to modify the genome of mammalian
      cells. The first method utilizes a new family of recombinant retroviruses (RRV)
      which leads to transduction in the mammalian genome of, not a complete
      recombinant retroviruses, but a single LTR (sLTR) that carries the foreign gene.
      Therefore, all cis viral regulatory elements of the virus, including those
      necessary for the control of transcription, reverse transcription and
      integration, are absent from the transduced material. In addition to being safer
      because of their inability to retrotranspose, the sLTR family of recombinant
      retrovirus (sLTR-RRV) overcome the problems associated with the presence of viral
      sequences that negatively control the expression of the transduced material in
      stem cells.

PMID- 8881276
TI  - [Experimental gene therapy in models of inflammatory arthritis].
AB  - Gene therapy is rheumatoid arthritis is presently in an experimental phase. Genes
      encoding for antiinflammatory proteins can be transfected in joint cells.
      Therefore gene encoding for interleukin-1 receptor antagonist has been
      transfected into synovial cells or into chondrocytes. Gene expression can be
      maintained as long as 8 weeks after cell transfer. We have reported that clinical
      and histopathological parameters of collagen-induced arthritis (an animal model
      of rheumatoid arthritis) can be reduced by engraftment of CHO cells transfected
      with genes encoding for antiinflammatory cytokines such as interleukine-4 or
      interleukine-13. Some of the questions which need to be assessed before planning
      clinical trial are the choice of vectors and the most efficient target cells; and
      the genes to be transfected have to be chosen among many candidates.

PMID- 8881277
TI  - [Immunotherapy of tumors expressing IGF-I].
AB  - Recently we demonstrated that rat glioma cells when transfected with a vector
      encoding antisense IGF-I c-DNA lost tumorigenicity and induced a tumor specific
      immune response involving CD8+ lymphocytes. Here we showed, using immunostaining
      flow cytometry analysis, that the transfected cell lines, rat C-6 glioma and rat
      LF hepatoma, expressed an increase level of MHC-class I, and even the amount of
      MHC-I was found to be higher in the transfected hepatoma, than in the transfected
      glioma cells. This increased expression of MHC-I could contribute to the final
      immune recognition of tumour immunogenicity.

PMID- 8881278
TI  - The genetic code and cyclic codes.
AB  - We proposed previously a cyclic code made of 22 triplets, which we now call the
      AB code. It is made up of the following chain: AUGGUGCCAUUCAAGACUAUGA. The
      letters A, U, C, G represent the classical symbols of the (purine and pyrimidine)
      bases of the genetic code. This chain presents the following features: (1) when
      it is in cyclic form, it begins with the initiation codon AUG, ends with the
      termination codon UGA, and it can be read triplet after triplet by choosing 1 and
      only 1 representative of each synonymy class in the classical degenerate genetic
      code made of 64 triplets. The chain, therefore, possesses 1 and only 1 codon for
      each amino-acid; (2) except for the doublet CG, triplets of the chain begin with
      the 15 other possible doublets of bases (satisfying the "wobble" hypothesis
      presented by Crick); (3) it corresponds (except for 1 base) to the "loop" part of
      the CEnothera mitochondrial Gly-tRNA; (4) it can be modified, without loss of the
      properties (1) and (2), in such a way as to have 15 bases in common with the loop
      part of other mitochondrial tRNA's considered as primitive, like Ala-, Pro- and
      Arg-tRNA; (5) it contains the most frequent triplets, but not the most rare ones,
      appearing in the genome of numerous species; (6) it exhibits a coherent internal
      structure with respect to the molecular weight of its triplets. This structure,
      also found in the loop part of mitochondrial tRNA's, contains an excess of AU
      bases with respect to GC bases. This fact has no explanation in the classical
      probabilistic model of the tRNA's. Therefore, we propose the cyclic AB code as a
      primitive genetic structure with the essential coding properties of the present
      genetic code.

PMID- 8881279
TI  - Horseradish peroxidase and glycosylated BSA induce nitric oxide production in
      murine macrophages.
AB  - The in vitro activation of murine macrophages by horseradish peroxidase (HRP)
      induced nitric oxide production in a dose-dependent manner, and increased the
      induction of NO-synthase by LPS. Nitrite production after HRP stimulation was
      inhibited by NG-monomethyl-L-arginine (NMMA), a specific inhibitor of NO
      synthase. Equivalent amounts of nitrite were obtained with native and heat
      inactivated HRP. High concentrations of mannose inhibited nitric oxide
      production, while the HRP inhibitor 3-aminotyrosine did not. Glycosylated serum
      albumin derivatives also induced murine macrophage NOS, probably by an
      interaction between carbohydrates and their specific cell membrane receptors. The
      inability of HRP apoprotein to stimulate NO production, and the specific
      inhibition of HRP-mediated activation of macrophages by hemin suggests that the
      heme moiety of this enzyme is involved in NO-synthase induction.

PMID- 8881280
TI  - [Complementarity of microscopies in the structural analysis of DNA minicircles
      associated to protein MC1].
AB  - Electron microscopy of DNA, either free or complexed with ligands, allows the
      analysis of local conformational variations along individual molecules. Electron
      microscopy is unique, in that it has the capacity to determine the average
      behaviour of a population of molecules observed individually, and can thus
      provide a better appreciation of variability within the series of molecules than
      biophysical or biochemical methods. Very encouraging results have been obtained
      by cryoelectron and near-field microscopies, especially atomic force microscopy,
      in parallel with traditional techniques for visualizing DNA molecules adsorbed
      onto a support film. Differences in sample processing procedures and image
      formation modes render these 3 types of microscopies complementary. The torsional
      stress of a DNA molecule together with a local curvature induced by the protein
      MC1 from archaebacteria, can be detected within minicircles comprising 207 base
      pairs.

PMID- 8881281
TI  - Partial sequence of the shrimp Penaeus notialis mitochondrial genome.
AB  - About half of the mitochondrial DNA of the shrimp Penaeus notialis (Crustacea:
      Decapoda) has been cloned (in 2 overlapping fragments of 7.9 kb and 1 kb) and
      partially sequenced. The gene content and arrangement are identical to that of
      the homologous domain in Drosophila yakuba. Intergenic nucleotides are scarce and
      a 982 bp non-coding sequence exhibit features similar to that of mtDNA control
      regions. The gene organization and the tRNA structures differentiate the Penaeus
      notialis mitochondrial genome from that of Artemia franciscana. Paraphyletism of
      crustacean mtDNA with respect to Insecta is discussed. A secondary structure of s
      rRNA is proposed.

PMID- 8881282
TI  - Is there a human [psi]?
AB  - The yeast Sup35p protein which is responsible for the [psi] phenotype, is a GTP
      binding protein involved in translation termination. It was suggested recently
      that the [psi] determinant has prion-like properties that were localized in the
      114 N-terminal amino acids of the protein. In this study, we show that the 5' end
      of the human SUP35 gene open reading frame is longer than previously reported by
      138 codons. This N-terminal sequence presents similarities with the N-terminus of
      S. cerevisiae Sup35p protein, involved in [psi] maintenance. By transfection of
      human cells and Western blotting, we demonstrate that translation is initiated at
      the first AUG encountered at the 5' end of the human SUP35 gene. The longest form
      of the protein, which contains the N-terminal extension, is the major form of
      Sup35p protein in non transfected cells. Moreover, an analog of the long form of
      Sup35p protein is found in various mouse tissues. We suggest that the protein
      encoded by SUP35 gene could have, at least in human, the properties described for
      the yeast [psi] element.

PMID- 8881283
TI  - Specific lipid protein interactions characterize 3 populations of clathrin coated
      vesicles involved in the LDL receptor traffic.
AB  - We have previously isolated 3 different populations of clathrin coated vesicles
      (CCV) involved in the LDL-receptor traffic in bovine adrenal cortex. We now show
      that each CCV type contains the transferrin-R and the CI-MPR, therefore, they
      provide a good model for studying the membrane organization that may govern their
      targeting in one of the biosynthetic, endocytic and/or recycling pathways.
      Transferrin--prototype of recylcing ligand--, and alpha adaptin, dynamin and the
      110 kDa phosphatidylinositol-3-kinase subunit--of the trafficking machinery--were
      mainly detected in only 2 of the vesicle populations which could be involved in
      the endocytic/recycling pathway. The third population which contained larger
      amounts of gamma adaptin and do not carry transferrin could be involved in the
      biosynthetic pathway. The vesicle lipid pattern and the saturation of their fatty
      acyl chains were analyzed and confirmed these results. The nature of the
      interactions between vesicle components was then determined using several classes
      of detergents. Only non ionic ones could solubilize the LDL-R in a complex with
      either alpha or gamma adaptin. In contrast, they dissociated clathrin or beta
      beta' adaptins. Taken together these results prompt us to suggest an integrated
      model for targeting in membrane traffic. Besides specific targeting signals
      carried by cargo proteins and recognized by proteins from the coat and the
      cytosolic trafficking machinery, lipids would play a key modulatory role. At each
      step in the membrane traffic, the proteins which carry multiple targeting signals
      would interact transiently with a specific set of lipids. This would result in
      the exposure of the appropriate targeting signals which could now become
      recognized by the proper targeting machinery.

PMID- 8881284
TI  - Pulse exposure to ionizing radiation elicits rapid changes in cellular
      radiosensitivity.
AB  - A linear electron accelerator, operated in a recurrent chopped mode, was used for
      time-resolved investigation of split-dose radiation recovery in 3 mammalian cell
      lines in vitro. The time intervals separating the sequential radiation exposures
      in this study ranged from fractions of a second to a few minutes. The primary
      pulse brought about rapid, synchronous oscillations of cellular radiosensitivity
      giving rise to a tetraphasic, W-shaped time-dependent profile whose first phase
      was accomplished by a large decrease of cell survival. Only the last phase
      correlated with sub-lethal damage repair determined by gamma-ray irradiation. The
      same profile was observed for the 3 cell lines investigated. However, the
      kinetics of the whole process varied extensively from one cell line to another.
      The first phase lasted 1 s only for Chinese hamster V79 fibroblasts, 6 s for
      human squamous carcinoma SQ20B cells, and as much as 25 s for human colon
      adenocarcinoma LoVo cells. The relative amplitude of this first phase grew with
      both the first and second radiation doses in the range explored. It is
      hypothesized that rapid oscillation of the cytotoxic potential of radiation may
      result from various mechanisms such as molecular recognition of radio-induced
      lesions, changes in chromatin structure, or differential activation of
      phospholipid-dependent transduction pathways.

PMID- 8881285
TI  - Spermatogenesis of the lizard Lacerta vivipara: histological studies and amino
      acid sequence of a protamine lacertine 1.
AB  - The lizard Lacerta vivipara is a seasonal breeder with a well characterized
      reproductive cycle. An histological study of the lizard testis has been performed
      at different stages of spermatogenesis and the nuclear basic proteins content was
      assessed by electrophoretical analysis. Two protamines, lacertines 1 and 2, are
      present in spermatozoa in April and May. We have isolated lacertine1 and
      characterized a protamine with a mass of 4,963.7 Da. Amino acid sequence of this
      protamine (41 residues) was established from data provided by automated Edman
      degradation. It is characterized by a basic amino acid stretch in the N- and C
      terminal regions and by a central part which only consists of 3 different
      intermingled amino acids. This protamine presents 62% homology with
      scylliorhinine Z3 from dog-fish Scylliorhinus caniculus and 58% homology with
      quail protamine. The reported lizard protamine sequence is the first reptilian
      protamine sequence available so far.

PMID- 8881286
TI  - [Large and small G proteins in vesicular transport].
AB  - The movement of proteins between compartments of the exocytic and endocytic
      pathways of eukaryotic cells is mediated by carrier vesicles. They bud from a
      donor compartment and are targetted to and fuse with the acceptor compartment.
      GTPases, proteins which bind and hydrolyze GTP, play key roles in the regulation
      of this vesicular protein transport. Heterotrimeric and small GTPases are
      involved in this vesicular traffic.

PMID- 8881287
TI  - [Effect of PML and PML-RAR on the transactivation properties and subcellular
      localization of steroid hormone receptors].
AB  - PML is a protein involved in the t (15, 17) translocation of promyelocytic
      leukemia and is mainly localized in nuclear bodies. Here we show that PML exerts
      a very powerful enhancing activity (up to 20-fold) on the transactivating
      properties of the progesterone receptor (PR) and has a similar effect on several
      other steroid hormone receptors. There is probably a direct or indirect
      interaction between PR and PML since when the latter was expressed at high
      concentrations it shifted PR into the nuclear bodies. Use of deletion mutants
      showed that both activation functions (AF1 and AF2) of PR as well as the coiled
      coil and His-Cys rich domains of PML were required for transcriptional
      enhancement. The fusion protein PML-RAR, which is not localized in nuclear
      bodies, also enhanced the transactivating activity of PR but this effect was
      totally suppressed by the administration of retinoic acid. PML, which is
      ubiquitously expressed, may thus be involved in the transactivation properties of
      steroid hormone receptors. This mechanism may also play a role in the oncogenic
      properties of PML-RAR and in their suppression by the retinoic acid.

PMID- 8881288
TI  - [Mutations of ACTH receptor gene and familial syndrome of glucocorticoid
      deficiency].
AB  - Familial isolated glucocorticoid deficiency syndrome is characterized by low
      cortisol plasma levels despite high ACTH levels without any stimulation of
      steroid production after ACTH administration. However, the mineralocorticoid
      function is well-preserved in this syndrome which indicates a specific resistance
      to ACTH. Recent cloning of the ACTH receptor allowed to study this receptor in
      this particular syndrome. After studying sixteen affected families, we have found
      three mutations in two patients from non-related families. One of these patients
      was a double heterozygote compound (C251F, G217fs) while the other one was
      homozygote for another mutation D107N. The mutant receptors were expressed in
      vitro in transfected M3 cells (S91 Cloudman cells) which represents a working
      expression system to express the ACTH receptor. Production of intracellular
      cyclic AMP was calculated in the presence of increasing concentrations of ACTH.
      The EC50 values were estimated (C251F: 3.5 +/- 0.9 x 10(-9) M, D107N: 3.0 +/- 0.9
      x 10(-9) M, G217fs: 4.8 +/- 0.9 x 10(-9) M) and comparison with the value
      obtained for the wild type ACTH receptor (5.1 +/- 0.9 x 10(-10) M) indicates a
      clear 6 to 9 shift to the right due to an impaired function of these mutant
      receptors. Such results were expected for the G217fs mutation, and could be
      explained by a decrease in ligand affinity or an impaired coupling to adenylate
      cyclase in the case of amino acid substitutions. A total of twelve mutations has
      been described in the literature although eight of them have not been tested in
      vitro until now.

PMID- 8881289
TI  - GH response to GH-releasing hormone (GHRH) in Alzheimer and vascular dementia.
      Relation with somatostatin cerebrospinal levels.
AB  - OBJECTIVE: To clarify the functional state of the somatotropinergic system in
      patients with Alzheimer's disease (AD) and in patients with vascular dementia
      (VD) in relation with somatostatin cerebrospinal levels. DESIGN We studied the GH
      response to GHRH in controls and in AD and VD patients and correlated their
      responses with somatostatin cerebrospinal levels. PATIENTS: Twelve control
      subjects and 56 patients, 28 with AD and 28 with VD, were studied. A GHRH test
      was performed in every case. One hundred mcg of GHRH was administered as a
      intravenous bolus and blood samples were drawn at -15, 0, 30, 60, 90 and 120
      minutes. Cerebrospinal fluid was obtained after lumbar puncture. Measurements of
      GH and somatostatin were determined by specific radioimmunoassay. RESULTS: The GH
      response to GHRH exhibited no difference between AD and VD patients (12.2 +/- 2
      mcg/l vs 9.9 +/- 1.8). There were 17 AD patients and 16 VD patients with
      exaggerated GH response to GHRH. There was no difference between cerebrospinal
      levels of somatostatin (30 +/- 2.1 pg/mL in AD patients vs 42 +/- 2.4 in VD
      patients), and there was no correlation among GH response to GHRH and
      cerebrospinal levels. CONCLUSION: In our study we observed no difference between
      the AD and VD patients in GH response to GHRH and no difference in somatostatin
      cerebrospinal levels in these patients.

PMID- 8881290
TI  - [Corticotropic adenoma in slow adrenal insufficiency].
AB  - This case report deals with an insulin-dependent diabetic patient suffering
      peripheral adrenal insufficiency who, after 12 years of substitutive treatment
      exhibited resistance to mineralo- and gluco-corticoids with relapse of
      melanodermia and plasma ACTH levels higher than 1500 pg/ml despite increasing
      doses. A corticotrop macroadenoma was diagnosed by MR imaging and functional
      tests and confirmed by surgical excision followed by disappearance of resistance.
      Pre-operative functional investigation show autonomisation of the adenoma but
      with some partial persisting regulation. This case report draws attention to this
      rare either complication or association which can occur in peripheral adrenal
      insufficiency.

PMID- 8881291
TI  - [Post-traumatic anterior pituitary insufficiency. Apropos of 2 cases].
AB  - Post-trauma hypopituitarism is rare. The frequency of pituitary lesions observed
      at autopsy contrasts with small number of clinical cases. We report two cases in
      a 38 and a 25-year-old patients who developed hypopituitarism two years after
      severe craniofacial trauma followed by early onset but transitory poluria
      polydypsia. Hormone explorations confirmed pituitary deficiency.
      Neuroradiological imaging, especially magnetic resonance imaging was normal with
      no intrasellar arachnoidocele.

PMID- 8881292
TI  - [Possible implication of TRH and dopamine in postnatal lactotropic hypoactivity
      in rats].
AB  - Our results show that pituitary glands of young rats (6 days) incubated in vitro,
      increase their PRL secretion in presence of TRH, this responses is greater than
      that in adult glands. Indeed, in presence of TRH 10(-7) M, PRL basal secretion of
      immature glands passes from 478.70 +/- 67.25 to 952.78 +/- 67.02, versus 5333.29
      +/- 75.456 and 6347.15 +/- 75.246 ng/mg protein at mature glands. The same dose
      of dopamine (DA), weakens the TRH stimulating effect by 60% and 40% respectively
      by young and adult pituitary glands. These results suggest that lactotroph
      insensitiveness to TRH injection observed during the first days of postnatal life
      at the rat, would not be explained by lactotroph failure, but by intervention of
      central and peripheral multiple modulator factors affecting lactotrophs
      reactivity, in particular the importance of dopaminergic control.

PMID- 8881293
TI  - [Postnatal lactotropic hypoactivity in rats: possible implication of VIP,
      endogenous opioids, dopamine and glucocorticoids].
AB  - In this study, the possible intervention of VIP (Vasoactive Intestinal Peptide),
      beta-endorphine, glycocorticoids and dopamine, in postnatal lactotrophs
      hypoactivity at the rat, was investigated. Our results show that the injection of
      VIP (40 micrograms/kg), beta-endorphine (125 micrograms/kg) or its antagonist,
      naloxone (2 mg/kg), does not provide a change in serum PRL before or after ether
      stress at 6-day-old rats. However, after adrenalectomy, 6 day-old neonates became
      sensitive to ether stress as do adults, while acute treatment with dexamethasone
      (2 mg/kg) or dopamine (1 mg/kg), abolished this response completely. Sulpiride
      injection (1 mg/kg), on the contrary potentialized response. This lactotroph
      insensitiveness to ether stress, TRH, VIP, and beta-endorphine, during the
      beginning of postnatal life in the rat, might be explained, partially, by the
      failure of stimulatory factors "PRF" (Prolactin Releasing Factors), together with
      strength of inhibitory factors "PIF" (Prolactin Inhibitory Factors), such as
      dopamine and glycocorticoids.

PMID- 8881294
TI  - [Can free T3 determination be affected by the presence of type 1 diabetes
      mellitus?].
AB  - Overall frequency of thyroid disease is increased in diabetic patients,
      especially in insulin-dependent diabetes. Free T3-assays are thus ordered more
      often in these populations. Attention has been drawn to the role of non
      esterified fatty acids in the different techniques used to assay free T3. The aim
      of this work was to evaluate the clinical revelance in a population of
      uncontrolled insulin-dependent diabetes. The results demonstrated that elevated
      non-esterified fatty acid levels observed in type 1 diabetes in modifications of
      free T3 assays, don't modified the different technics of free T3.

PMID- 8881295
TI  - [The brain in children and the human immunodeficiency virus (HIV-1)].

PMID- 8881296
TI  - [Determination of the posology of drugs in pediatry].

PMID- 8881297
TI  - [Digestive manifestations in hemolytic uremic syndrome in children].
AB  - BACKGROUND: Gastro-intestinal manifestations are relatively frequent during the
      course of hemolytic uremic syndrome (HUS), some of them requiring special
      supportive care. This work was aimed at retrospectively studing gastrointestinal
      manifestations of HUS and determining their place in the prognosis. PATIENTS:
      Thirty-seven children aged 4 months to 11 years (22 girls and 15 boys) were
      included in the study. RESULTS: All children but one had gastrointestinal
      prodromes. During the course of HUS, various manifestations were seen: bloody
      diarrhea in 32% of patients, ileo-ileal intussusception in 3%, rectal prolapse in
      8% and hepatic cytolysis in 38%. Seven patients with bloody diarrhea had a
      complicated course, lethal in one. Comparison between these seven children and
      the 30 others revealed some indicators of severe gut involvement: female sex,
      short duration of gastrointestinal prodromes, hemorrhagic colitis with rectal
      prolapse, high WBC count, high neutrophils count and less important degree of
      anemia at admission. Severity of the gastrointestinal lesions was correlated with
      that of the outcome of the renal disease. CONCLUSION: Gastrointestinal tract is
      frequently affected in HUS and severe complications can appear, potentially
      leading to death. Total parenteral nutrition could prevent occurrence of
      gastrointestinal complications. Severe gastrointestinal lesions are associated
      with a poor renal outcome.

PMID- 8881298
TI  - [Dermatitis herpetiformis occuring in patients with celiac disease in childhood].
AB  - BACKGROUND: Dermatitis herpetiformis (DH) is a chronic papulovesicular immune
      mediated disorder associated with gluten-sensitive enteropathy. We report eight
      cases in which DH appeared many years after celiac disease (CD) in child.
      PATIENTS AND METHODS: The diagnosis of CD was based on histological features of
      total or subtotal villous atrophy, full remission after withdrawal of gluten from
      the diet, and eventually circulating antibodies (IgA gliadin, antireticulin and
      antiendomysium) at the time of diagnosis and their disappearance under gluten
      free diet. The diagnosis of DH was made from clinical findings, histological
      examination of the involved skin and direct immunofluorescence microscopy of
      normal or perilesional skin. HLA class II typing was performed in five patients.
      DRB1, DQA1, DQB1 and DBP1 alleles were studied. RESULTS: DH appeared between 3
      and 22 years after the initial diagnosis of CD. Five patients did not show at
      that time any digestive symptoms. In three cases, a break in the gluten-free diet
      or a recent revival of the normal diet preceded the rash. In only one case, DH
      appeared while the patient was under gluten-free diet. In three patients, the
      rash appeared many years after the gluten-free diet had been stopped. Phenotype
      DR3 and/or DR7 of the celiac disease could be found in four of the five patients
      studied; three of them were found to bear DQW2. The DR2 allele was not found in
      any of the five tested patients. DISCUSSION: These eight cases illustrate the
      absence of precise nosological barrier between gluten-sensitive enteropathy of
      the DH and that observed in CD. The presence of the DR7 allele, and especially
      the absence of the DR2 allele, could explain the particularly severe and
      symptomatic course of the enteropathy in these patients. The delay in the
      appearance of DH, after a very variable period of normal diet, could correspond
      to the necessary time for progressive accumulation of IgA (or immune complex IgA
      gluten) in the skin after a digestive sensitization to gluten. The preventive
      role of gluten-free diet is thus probable. CONCLUSION: CD and DH likely
      correspond to two different stages of the same disease, thus requiring a
      prolonged follow-up of both digestive and skin tissues. Long-term eviction of
      gluten to prevent eventual DH must be balanced with the demand and the cost of
      such a diet.

PMID- 8881299
TI  - [Odontochondrodysplasia].
AB  - BACKGROUND: Dentinogenesis imperfecta is exceptionally associated to
      chondrodysplasia. The aim of this work is to present four cases of such an
      association. CASE REPORT: These four children (three boys; one girl) suffered
      from growth retardation, ligamentous hyperlaxity, scoliosis. Main features were
      present since the first months of life. Dentinogenesis imperfecta was more marked
      on the first teeth. On X-rays, all patients had short tubular bones, more
      pronounced at the level of the middle segment of their limbs, with irregular
      metaphyses. Cone-shaped epiphyses were present on the hands. Iliac wings were
      square-shaped and vertebral bodies had a posterior wedging. CONCLUSION: These
      four cases, including two previously published as Goldblatt's syndrome, share the
      same findings as another case described by this author. We propose the name of
      odontochondrodysplasia for this apparently unfortuitous association:
      dentinogenesis imperfecta and chondrodysplasia.

PMID- 8881300
TI  - [School at the end of life. What objectives what hope?].
AB  - BACKGROUND: School intervention programs for children and adolescents with cancer
      have been developed in France during the last years. Their primary objective is
      to improve the pschychosocial adaptation of these children to normal life through
      school integration. These programs are however inadequate for these children who
      will ultimately die from their disease and may require a specific school
      intervention. MATERIAL AND METHODS: School data from 30 children requiring
      palliative care were prospectively collected. School interest, its evolution and
      specific adaptations according to the child's status were analysed. RESULTS:
      Sixty per cent of the children showed a continuous desire for school education
      throughout their life's end. Reading, mathematics and computer work were the most
      favorite topics. Physical disability and fatigue may change their request during
      the evolution of the disease. School refusal occurred in 40% of the children and
      is mainly due to other extra-academic topics, or related to uncontrolled pain.
      CONCLUSION: Objectives of life's end school are different from educational
      programs proposed for children with cancer. They must be part of palliative care
      and have to be defined as a specific entity.

PMID- 8881301
TI  - [Superior sagittal sinus thrombosis in children during the first year of life:
      clinical aspects, imaging and development].
AB  - BACKGROUND: Thrombosis of the intracranial sinuses and veins may be septic or
      aseptic, and in the latter case are often due to alteration in hemodynamics. It
      may also be seen in young babies without known predisposing factors. PATIENTS:
      From 1988 to 1994, 11 children had cerebral venous thrombosis (longitudinal
      sinus) in the first year of their life. Their ages ranged from two days to 11
      months. Transient seizures, lethargy, pseudo tumor cerebri were the first
      clinical symptoms. The presence of longitudinal sinus thrombosis was suggested by
      unenhanced CT scan, confirmed by colour doppler flow imaging and magnetic
      resonance angiography, with absence of blood flow in the longitudinal sinus.
      Repeated doppler flow imaging showed thrombus resolution within 3 weeks.
      Thrombosis was associated with predisposing factors in seven cases and appeared
      idiopathic in the four others. CONCLUSION: Diagnosis of longitudinal sinus
      thrombosis can be made more accurately and noninvasively by colour doppler flow
      and angio-MRI. Treatment with anticoagulants appears unnecessary and dangerous in
      idiopathic forms.

PMID- 8881302
TI  - [Primary leiomyosarcoma of the small intestine in a child].
AB  - BACKGROUND: Leiomyosarcomas of the digestive tract are very rare in children.
      They must be differentiated from benign tumors (leiomyoma, schwannoma...) and
      from other malignant tumors, sometimes with the aid of immuno-histochemical
      study. CASE REPORT: A five-year old girl suffered from an abdominal mass
      associated with fever and alteration of the general condition. An ileal tumor, 8
      cm in diameter, was resected. Histological and immunohistochemical studies (anti
      vimentin antibodies, anti-actin antibodies and PS100) confirmed the diagnosis of
      leiomyosarcoma. Uncomplete adjuvant chemotherapy failed to prevent relapse of the
      tumor. CONCLUSION: This case confirms the bad prognosis of such a tumor.

PMID- 8881303
TI  - [Invasive Pseudomonas aeruginosa and Ecthyma gangrenosum infection in a child
      without risk factors].
AB  - BACKGROUND: Pseudomonas aeruginosa sepsis, well known in immunocompromised
      patients, is rare in previously healthy children. CASE REPORT: A previously
      healthy 4 month-old boy was admitted with the suspicion of meningococcal
      septicemia. Three days prior to admission, he had developed high fever and two 4
      cm-diameter skin lesions on his right leg, with dark red colour and a central
      haemorrhagic blister. He subsequently developed generalized seizures; meningitis
      and urinary tract infection were excluded. Despite topical therapy with an
      antistaphylococcal drug skin lesions extended, particularly at the level of the
      head. The patient was given oral amoxicillin-clavulanate, but his condition
      worsened; he was transferred to our intensive care unit with septic shock and a
      diagnosis of meningococcemia. Blood cultures grew Pseudomonas aeruginosa. Despite
      intensive therapy and appropriate antibiotic therapy, the patient died.
      CONCLUSION: To allow early diagnosis and adequate treatment, it is mandatory to
      diagnose Ecthyma gangrenosum as the most frequent manifestation of invasive
      infection with Pseudomonas aeruginosa.

PMID- 8881304
TI  - [Neurologic manifestations of Mycoplasma pneumoniae infections].
AB  - BACKGROUND: Some neurological manifestations associated with Mycoplasma
      pneumoniae infection have been reported, such as meningoencephalitis,
      cerebellitis, aseptic meningitis, polyradiculopathy, transverse myelitis, cranial
      nerve palsies and myositis. CASE REPORT: Case 1. A 10 year-old boy had an acute
      pneumonia that was subsequently proven to be due to Mycoplasma pneumoniae
      infection. This infection was resistant to macrolid administration for 1 week
      requiring the administration of vibramycin instead. At that time, the patient
      developed an aseptic meningitis syndrome and a severe cerebellitis. He completely
      recovered within a few days. Case 2. A boy was admitted because he suffered from
      polyradiculopathy that had appeared during an acute episode of pneumonia. The
      neurological involvement extended to cranial nerves, then subsequently completely
      disappeared. Seroimmunological studies confirmed the Myoplasma pneumoniae
      infection. CONCLUSION: The mechanism of these classical but rare neurological
      manifestations remains unclear.

PMID- 8881305
TI  - [Sarcoidosis with hematologic involvement and hypogammaglobulinemia].
AB  - BACKGROUND: Hematological changes are uncommon in childhood sarcoidosis. CASE
      REPORT: Case 1. This patient developed severe hemolytic anemia associated with
      splenomegaly at the age of 11 months. A second episode of hemolysis was seen at
      the age of 6 years; it was associated with thrombocytopenia and
      hypogammaglobulinemia. A partial splenectomy permitted histological diagnosis of
      sarcoidosis that was confirmed by elevated angiotensin-converting enzyme level,
      and subsequently developement of pulmonary involvement. Case 2. This boy suffered
      from autoimmune hemolytic anemia and thrombocytopenia associated with
      splenomegaly at the age of 3 years. At the age of 7 years, he had splenomegaly,
      enlarged cervical and lomboaortic lymph nodes and hypogammaglobulinemia.
      Diagnosis of sarcoidosis was made from lymph nodes and spleen biopsies after
      splenectomy; the patient had increased angiotensin-converting enzyme
      concentration, and subsequently developed specific renal involvement. CONCLUSION:
      Association of hemolytic anemia, thrombocytopenia, hypogammaglobulinemia and
      splenomegaly should suggest the diagnosis of sarcoidosis and could be considered
      as part of the disease spectrum.

PMID- 8881306
TI  - [Developmental dysphasia].
AB  - Developmental dysphasia is characterized by severe, specific and unexplained
      developmental language impairment. Phonologic and syntactic disorders of
      expressive language and perceptual deficit are almost always present. Moreover,
      certain specific linguistic symptoms are particular to each dysphasic child,
      explaining the efforts to classify different forms of dysphasia. The most
      important point is to separate receptive dysphasia from the expressive on the one
      hand, and severe forms from the mild which are closed to "simple language delay",
      on the other. The evolution of oral language is variable, but often long and
      difficult, with persistent linguistic deficit. Reading and writing acquisition is
      usually difficult, although very important for the socio-professional outcome and
      language improvement. The etiology remains unknown and is probably
      multifactorial. One pathogenic hypothesis is based on the absence of the usual
      hemisphere specialisation related to various prenatal or postnatal events. A
      genetic basis seems likely for certain dysphasic children. Development of
      knowledge about this condition and improvement of both speech therapy and
      teaching are essential for the outcome of these otherwise intelligent and normal
      children.

PMID- 8881307
TI  - [Current aspects of Turner syndrome].
AB  - Recent progress in the clinical, genetic and therapeutic knowledges of Turner's
      syndrome are presented. The quality of life of Turner's syndrome can be much
      improved by early treatment with recombinant human growth hormone which
      significantly increases the patient's final height, and appropriate oestrogenic
      therapy at pubertal and adult ages. However, this requires an early diagnosis.
      Consequently, a karyotype must be performed in every girl with delayed growth,
      even in the absence of clinical features of the Turner's syndrome.

PMID- 8881308
TI  - [Sleeping position, prevention of sudden death syndrome and gastroesophageal
      reflux].
AB  - Based on results of epidemiological studies, dorsal or lateral sleeping positions
      are now recommanded in the prevention of sudden infant death syndrome (SIDS).
      This raises an ethical question about the attitude towards the ventral
      positioning therapy for gastroesophageal reflux (GOR). The consensus conference
      considers that the ventral position should only be recommanded in GOR when the
      benefit appears to outweigh the risk of SIDS that it induces. The conference
      proposes that for infants with simple uncomplicated reflux, sleeping in the prone
      position should not be introduced in the first line treatment. Prone positioning
      should be restricted to complicated cases resistant to dietary and medical
      measures.

PMID- 8881309
TI  - [Opinions and practices of family physicians regarding measles-mumps-rubella
      vaccination].
AB  - BACKGROUND: Measles-mumps-rubella immunization rates among young children depend
      on the awareness and responsibility of parents and physicians. In order to
      improve immunization programmes, it is important to enhance our knowledge about
      attitudes of physicians in regard to MMR immunization. A random sample of 1013
      general practitioners was interviewed by telephone in December 1994, with the
      collaboration of the BVA Institute. The large majority of French physicians (86%)
      have a favourable opinion about MMR immunization that they systematically propose
      to each child aged 12-24 months. However, barriers remain among some physicans.
      Favourable opinion about MMR immunization to infants was less frequent among
      physicians aged 41-50 years, homeopaths, those practicing in Southern France,
      those asking for higher payment to patients, those who are treating a small
      proportion of patients receiving public medical aid, those not convinced about
      the role of physicians in health education, those who experienced side-effects of
      immunization and those who are not personnally immunized against hepatitis B.
      Eradication of measles, mumps and rubella in France will be only achieved through
      a stronger and well-argumented information of physicians supported by health
      professional organizations.

PMID- 8881310
TI  - [Apropos of peanut allergy].

PMID- 8881311
TI  - [Neonatal extradural hematoma].

PMID- 8881312
TI  - [Treatment with ganciclovir of congenital cytomegalovirus infections].

PMID- 8881313
TI  - [Incidence of sudden infant death and outcome of sleep position in Seine
      Maritime].

PMID- 8881314
TI  - [Self-controlled analgesia and ambulatory palliative care].

PMID- 8881315
TI  - [Story of antifreeze].

PMID- 8881316
TI  - [Severe, isolated and prolonged febrile syndrome revealing sarcoidosis in a
      child].

PMID- 8881317
TI  - Mechanisms of facilitation in primed perceptual identification.
AB  - We investigated the mechanism that produces priming in perceptual identification.
      In Experiment 1, subjects studied a series of compound words (e.g., OUTDOOR,
      SIDELINE); in Experiment 2, subjects studied a series of pictures (photographs)
      of objects. All subjects later received perceptual identification tests in which
      old (primed) and new (unprimed) words (Experiment 1) or pictures (Experiment 2)
      were presented for varying durations and masked. In both experiments, performance
      for primed and unprimed stimuli was predicted essentially perfectly by a model
      that assumes that prior exposure to a stimulus results in increased visual
      information-acquisition rate when it is subsequently encountered. An ancillary
      purpose of Experiment 1 was to test whether or not priming occurs for recombined
      words (e.g., OUTLINE); there was no evidence for such priming at any exposure
      duration.

PMID- 8881318
TI  - A template-matching pandemonium recognizes unconstrained handwritten characters
      with high accuracy.
AB  - Psychological data suggest that internal representations such as mental images
      can be used as templates in visual pattern recognition. But computational studies
      suggest that traditional template matching is insufficient for high-accuracy
      recognition of real-life patterns such as handwritten characters. Here we explore
      a model for visual pattern recognition that combines a template-matching and a
      feature-analysis approach: Character classification is based on weighted evidence
      from a number of analyzers (demons), each of which computes the degree of match
      between the input character and a stored template (a copy of a previously
      presented character). The template-matching pandemonium was trained to recognize
      totally unconstrained handwritten digits. With a mean of 37 templates per type of
      digit, the system has attained a recognition rate of 95.3%, which falls short of
      human performance by only 2%-3%.

PMID- 8881319
TI  - Attentional focusing with quantifiers in production and comprehension.
AB  - There is a very large number of quantifiers in English, so many that it seems
      impossible that the only information that they convey is about amounts. Building
      on the earlier work of Moxey and Sanford (1987), we report three experiments
      showing that positive and negative quantifiers focus on different subsets of the
      logical possibilities that quantifiers allow semantically. Experiments 1 and 2
      feature a continuation task with quantifiers that span a full range of
      denotations (from near 0% to near 100%) and show that the effect is not
      restricted to quantifiers denoting small amounts. This enables a distinction to
      be made between generalization and complement set focus proper. The focus effects
      extend to comprehension, as shown by a self-paced reading study (Experiment 3).
      It is noted that the focus effects obtained are compatible with findings from
      earlier work by Just and Carpenter (1971), which used a verification paradigm,
      and in fact these effects constitute a direct test of inferences Just and
      Carpenter made about mechanisms of encoding negative quantifiers. A related but
      different explanation is put forward to explain the present data. The experiments
      show a quantifier function beyond the simple denotation of amount.

PMID- 8881321
TI  - Accessing short-term memory with semantic and phonological information: a time
      course analysis.
AB  - The time course for accessing short-term memory representations on the basis of
      item, phonological, and semantic information was measured with a speed-accuracy
      tradeoff (SAT) variant of a recognition probe task. Subjects studied 5-word lists
      and then judged whether a test word (1) was in the study list (item judgment);
      (2) rhymed with a word in the study list (rhyme judgment); or (3) was a synonym
      of a word in the study list (synonym judgment). Analysis of the SAT retrieval
      functions demonstrated that judgments based on phonological and semantic
      information were slower and less accurate than judgments based on composite item
      representations. The slower retrieval dynamics for rhyme and synonym judgments
      suggest that judgments based on component properties of the memory trace are
      mediated by either a generate or recall process distinct from the parallel or
      direct-access mechanism used in item judgments.

PMID- 8881320
TI  - Retrieval processes in arithmetic production and verification.
AB  - To investigate whether arithmetic production and verification involve the same
      retrieval processes, we alternated multiplication production trials (e.g., 9 x 6
      = ?) with verification trials (4 x 9 = 36, true or false?) and analyzed positive
      error priming. Positive error priming is the phenomenon in which errors
      frequently match correct answers from preceding problems. Production errors were
      strongly primed by previous production trials (the error-answer matching rate was
      about 90% greater than expected by chance), but production errors were not
      strongly primed by previous verification trials (approximately 13% above chance).
      Conversely, false-verification errors were primed by previous verification trials
      (approximately 25% above chance), but not by production trials. The results
      indicated that arithmetic production and verification were mediated by different
      memory processes and suggest a familiarity-based over a retrieval-based model of
      arithmetic verification.

PMID- 8881322
TI  - On the relative and absolute strength of a memory trace.
AB  - Subjects studied either an 8- or 16-word list and later recalled the items while
      a voice key recorded each response latency. The trials were partitioned by recall
      total in order to examine the means and distributions of both latencies and
      interresponse times as a function of recall total. Each analysis was consistent
      with the view that an item's absolute strength determines whether it is recalled
      whereas an item's relative strength determines when it is recalled. In addition,
      mean latency was effectively proportional to study list length yet independent of
      recall total. All of the analyses were consistent with the view that the set of
      study items is sampled according to a relative-strength rule until all items are
      found and that a sampled item is recovered into consciousness only when its
      absolute strength exceeds a fixed threshold.

PMID- 8881323
TI  - Tests of encoding tradeoffs between item and associative information.
AB  - The assumption that item and associative information are processed separately and
      that there is a tradeoff in the amount of each type of information that can be
      encoded in a given study interval (e.g., Anderson & Bower, 1972; Murdock, 1982,
      1992) was examined. When item information was emphasized at study, recognition
      memory for associative information was poor, demonstrating that item information
      can be emphasized over associative information. In contrast, when associative
      information was emphasized, associative recognition greatly improved but item
      recognition did not suffer. This pattern of results was found at both fast and
      slow presentation rates, and for both high and low word concreteness and word
      frequency. Measures of confidence and response latency were also consistent with
      this pattern. Thus, the encoding of associative information did not measurably
      diminish item recognition performance.

PMID- 8881324
TI  - Accessing the particular from the general: the power of distinctiveness in the
      context of organization.
AB  - Recall is inversely related to the number of items sharing a cue. The limiting
      case of unique cue-target relationships supports extremely high levels of recall,
      particularly when the cue is self-generated. This fact is incongruous with the
      importance assigned to the construct of organization in memory theory. Further,
      self-generated unique cue-target relationships tend to be idiosyncratic, implying
      that the power of unique cues should be limited to cases of self-cued memory. The
      experiments presented here suggest a role for organization that reconciles the
      fact of unique cue effectiveness with the importance of organization to memory.
      Two new findings are reported: Unique cue production enhances target encoding;
      and general cues can access particular encodings. The data are further tribute to
      the importance of simultaneous organizational and distinctive processing and
      recommend a new perspective on the function of organization in memory.

PMID- 8881325
TI  - Instability of individual differences in the association between confidence
      judgments and memory performance.
AB  - There are large individual differences in the degree of association between the
      accuracy of memories and subjective confidence in those memories. Are these
      differences stable within the same test, and between alternate forms of a test?
      In Experiment 1, college students were tested on 3 recognition memory tasks, then
      retested 2 weeks later on alternate forms of the same tasks. The relationship
      between confidence judgments and recognition performance displayed low split-half
      stability and low alternate-forms stability. A second experiment with elderly
      adults replicated these findings. In a third experiment, college students
      recalled answers to general knowledge questions and rated confidence in the
      correctness of each answer. Individual differences in the association between
      confidence and recall performance were not stable across the odd- and even
      numbered items on the test. These data indicate the need for the development of
      procedures that will produce stable estimates of individuals' metacognitive
      accuracy.

PMID- 8881326
TI  - Commonalities and differences in similarity comparisons.
AB  - Similarity is a central component of many cognitive processes. Current research
      suggests that similarity is well characterized as a comparison of structured
      representations. This process yields commonalities, differences related to the
      commonalities (alignable differences), and differences not related to the
      commonalities (nonalignable differences). In the first study, further evidence
      for this tripartite distinction is provided in a commonality and difference
      listing study involving pairs of pictures. This study indicates that alignable
      differences rather than nonalignable differences are central to the comparison
      process by virtue of their connection to the commonalities. The second study
      further demonstrates that alignable differences count more against the similarity
      of a pair than do nonalignable differences. We end by discussing implications of
      the distinction between alignable and nonalignable differences for other
      cognitive processes involving comparisons.

PMID- 8881327
TI  - Beyond belief bias: reasoning from conceptual structures by mental models
      manipulation.
AB  - Mental models constitute an alternative to the rule-based systems in the
      explanation of human reasoning (Johnson-Laird, 1983). In this paper, we claim
      that the concept of believability generally used to categorize content and
      context effects is of little use within a semantic theory. Thus, we propose the
      use of categories that are directly extracted from subjective relations among
      concepts within the reasoning problem. We demonstrate that manipulations based on
      this kind of categorization produce predictable patterns of responses in
      reasoning problems. We present two experiments to test our predictions, using
      conditional and syllogistic reasoning problems, and in both cases, we demonstrate
      the influence of conceptual knowledge not only in natural contexts, but also in
      experimentally created artificial contexts.

PMID- 8881328
TI  - Carotenoids in photosynthesis.

PMID- 8881329
TI  - Reversible photobleaching of fluorescein conjugates in air-saturated viscous
      solutions: singlet and triplet state quenching by tryptophan.
AB  - Fluorescence recovery after photobleaching (FRAP) measurements on air-saturated
      aqueous solutions of fluorescein made viscous with glycerol or sucrose revealed a
      rapid component of fluorescence recovery with exponential time constants of 30
      120 microseconds at viscosities of 15-300 cP. The rapid recovery process was not
      related to fluorophore translational diffusion and was insensitive to fluorophore
      concentration and the additive used to increase solution viscosity. At constant
      viscosity, the rate of reversible photobleaching recovery increased 2.5-fold in
      an O2- vs N2-saturated solution. The relative efficiency of reversible-to
      irreversible photobleaching decreased with increasing photobleaching time and/or
      beam intensity. Reversible photobleaching was also detected for conjugates of
      fluorescein with dextrans and proteins in viscous media. In screening triplet
      state quenchers that might influence the reversible recovery, it was found that
      tryptophan enhanced the rate of reversible photobleaching recovery (two-fold
      increase at 8 mM) and quenched the fluorescein singlet state (Stern-Volmer
      constant, 12 M-1). Analysis of fluorescein lifetimes and photobleaching
      parameters for a series of fluorescein-labeled proteins with different numbers of
      tryptophans were also carried out. The results provide evidence for an oxygen
      dependent, reversible photobleaching mechanism for the fluorescein chromophore
      involving triplet state relaxation. The identification of reversible fluorescein
      photobleaching has important implications for FRAP measurements of rapid solute
      diffusion in biological systems.

PMID- 8881330
TI  - Supramolecular cationic tetraruthenated porphyrin induces single-strand breaks
      and 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in DNA in the presence of
      light.
AB  - The aim of this investigation is the evaluation of DNA interaction of with
      tetraruthenated porphyrin (TRP) and of DNA damage in the presence of light.
      Direct-fluorescence and electronic absorption measurements after incubation of
      DNA with TRP indicate strong binding between pBR322 DNA or calf thymus DNA with
      the modified porphyrin. Exposure of pBR322 DNA to TRP (up to 3 microM) and light
      leads to single-strand break formation as determined by the conversion of the
      supercoiled form (form I) of the plasmid into the nicked circular form (form II).
      Oxidative DNA base damage was evaluated by the detection of 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodGuo) after irradiation of calf thymus DNA in the presence
      of the TRP. The data demonstrated a dose and time dependence with each type of
      DNA damage. These data indicate (1) a specificity of the binding mode and (2)
      type I and II photoinduced mechanisms leading to strand scission activity and 8
      oxodGuo formation. Accordingly, singlet molecular oxygen formation, after TRP
      excitation, was confirmed by near-infrared emission. From these investigations a
      potential application of TRP in photodynamic therapy is proposed.

PMID- 8881331
TI  - Induction of lambda prophage by 213 nm laser radiation: a quantitative comparison
      with 193 nm excimer radiation using image analysis.
AB  - We compared the DNA damage produced by radiation from two UV laser wavelengths,
      213 nm and 193 nm, with that produced by noncoherent 254 nm radiation. Following
      irradiation of Escherichia coli BR339, a bacteriophage lambda lysogen containing
      the lacZ gene, pro-phage induction was measured by assaying for beta
      galactosidase. Because of the limited penetration by UV laser wavelengths an agar
      overlay of the lysogen was used as the irradiation target. Irradiation of 254 nm
      was performed in buffer suspension followed by transfer of 5 microL spots onto
      assay plants. Computer image analysis was used to monitor the rate of product
      formation, observed as an increase in optical density of the irradiated zones on
      assay plates. We found that the rate of product formation was a more reproducible
      unit of comparison than the optical density present at the end of the reaction.
      Although the rate of product formation was not linearly related to enzyme
      concentration, the data could be fit to a simple logarithmic function. Using this
      method, we concluded that the DNA damaging ability of 213 nm radiation was 10
      times more efficient than 193 nm radiation and about 100 times less efficient
      than 254 nm noncoherent radiation.

PMID- 8881332
TI  - UVA-potentiated damage to calf thymus DNA by Fenton reaction system and
      protection by para-aminobenzoic acid.
AB  - Calf thymus DNA was irradiated with low-intensity UVA (main output at 365 nm, 2
      mW cm-2 or 36 kJ m-2 for 30 min), and the role of metal ions, hydrogen peroxide
      and reactive oxygen species (ROS) was examined. DNA damage was measured as
      thiobarbituric acid-reactive substances (possibly from degradation of
      deoxyribose) and as changes in ethidium bromide-DNA fluorescence due to unwinding
      from strand breaks. Under the present experimental conditions, UVA alone or in
      the presence of H2O2 had no effect on DNA but slightly enhanced the damage by
      iron/EDTA. Ultraviolet A strongly enhanced DNA damage (ca four- to five-fold) by
      the Fenton reaction system (50 microM Fe2+/100 microM EDTA + 0.5 mM H2O2). The
      results suggest that the Fenton reaction system was "photosensitized" to damage
      DNA by low-intensity UVA radiation. The enhanced damage by UVA was attributed in
      part to the reduction of Fe3+ to Fe2+. Ultraviolet A had no effect when iron
      (ferric or ferrous) ions were replaced by Cu2+, Zn2+, Mn2+ or Cd2+. The ROS
      involved in the UVA-enhanced damage to DNA by the Fenton reagents were OH and, to
      a lesser extent, superoxide anions. The UVA-potentiated DNA damage by the Fenton
      reaction system was then used to examine the protective effect of para
      aminobenzoate (PABA), a UVB-absorbing sunscreen that protects against
      photocarcinogenesis in hairless mice. The results show that PABA and mannitol
      dose-dependently inhibited the damage with concentrations required for 50%
      inhibition at 0.1 mM and 3 mM, respectively. The protection by PABA was
      attributed to its radical-scavenging ability because PABA does not absorb light
      in the UVA region. These findings may be relevant to the biological damage by UVA
      and suggest that PABA is useful in protection against photocarcinogenesis by wide
      range UV radiation.

PMID- 8881333
TI  - Purification and partial characterization of (6-4) photoproduct DNA photolyase
      from Xenopus laevis.
AB  - The (6-4) photoproduct DNA photolyase was detected in two vertebrate animals
      Crotalus atrox (rattlesnake) and Xenopus laevis (South African clawed toad). The
      enzyme was extensively purified from X. laevis and characterized. The highly
      purified enzyme is fluorescent with an excitation maximum at 420-440 nm and
      emission maximum at 460-480 nm. The photorepair action spectrum matches the
      fluorescence excitation spectrum with a 430 nm maximum.

PMID- 8881334
TI  - Investigating the red shift between in vitro and in vivo urocanic acid
      photoisomerization action spectra.
AB  - Trans-urocanic acid (UCA) is found in the upper layer of the skin and UV
      irradiation induces its photoisomerization to cis-UCA. Cis-UCA mimics some of the
      immunosuppressive properties of UV exposure. The wavelength dependence for in
      vitro photoisomerization of trans-UCA (15 microM) over the spectral range 250 nm
      340 nm (10 nm intervals) was determined. The action spectrum revealed that
      maximal cis-UCA production occurred at 280 nm, which is red-shifted by 10-12 nm
      from its absorption peak at 268 nm and differs markedly from the reported action
      spectra for cis-UCA production in mouse skin in vivo, which peaks at 300-310 nm.
      The reasons for the red shift between the in vitro and in vivo action spectra are
      not clear. There is limited evidence suggesting that the UV absorption maximum of
      trans-UCA red shifts from 268 nm in vitro to 310 nm on interaction with stratum
      corneum proteins in vivo. This phenomenon was investigated by applying trans-UCA
      (2.5 mg/cm2) in an oil emulsion to isolated human stratum corneum. After
      incubation at 37 degrees C for 1 h, the absorption spectra of stratum corneum
      with UCA and with oil only were compared using a Xe arc source and a
      spectroradiometer. A moderate red shift in trans-UCA absorption from
      approximately 268 nm to 280 nm was observed. In summary, we suggest that the 10
      12 nm red shift between the UCA absorption spectrum peak and the action spectrum
      peak in vitro may be accounted for by the wavelength dependence of quantum yields
      reported over the 254-313 nm range. The red shift between the in vitro and in
      vivo photoisomerization action spectra may result from the 10 to 12 nm red shift
      in the absorption of UCA in association with stratum corneum proteins, combined
      with increasing quantum yields over the 254-313 nm range.

PMID- 8881335
TI  - Isopimpinellin is not phototoxic in a chick skin assay.
AB  - Synthetic isopimpinellin (5,8-dimethoxypsoralen), confirmed to contain as
      impurities only trace quantities at most of psoralen, bergapten (5
      methoxypsoralen) and xanthotoxin (8-methoxypsoralen), is not phototoxic when
      tested in a chick skin bioassay system. These findings are at variance with
      earlier studies showing isopimpinellin to be phototoxic against chick skin and
      support the conclusion that isopimpinellin is photobiologically inactive. As
      recently proposed by others, the several reports of isopimpinellin photoactivity
      are most likely attributable to contamination by small amounts of highly active
      psoralens such as bergapten or xanthotoxin.

PMID- 8881336
TI  - Elastic fiber-associated proteins of skin in development and photoaging.
AB  - We sought to use antibodies against structural (tropoelastin fibrillin) and
      nonstructural (decay-accelerating factor [DAF], serum amyloid P -SAP- components
      of elastic fibers to characterize fiber structure in neonatal skin, normal adult
      skin and adult skin with solar elastosis from advanced photoaging. We found by
      immunohistochemistry and by western blotting that DAF, unlike SAP, is present on
      cutaneous elastic fibers in neonates and young children, suggesting that DAF may
      play an early, integral role in protecting elastic fibers from destruction by
      complement. The most superficial portion of oxytalan fibers stained with
      antibodies against fibrillin and DAF, while anti-tropoelastin stained only the
      deeper portion of oxytalan fibers. This suggests that deep oxytalan fibers are
      composed of both elastin and microfibrils, while the most superficial component
      is composed solely of microfibrillar proteins. Solar elastosis showed increased
      fibrillin, DAF, tropoelastin and SAP. Thus, solar elastosis is composed of both
      microfibrillar and elastin proteins.

PMID- 8881337
TI  - A comparison of functional bladder damage after intravesical photodynamic therapy
      with three different photosensitizers.
AB  - The influence of type of photosensitizer, drug and light dose, and time interval
      between photosensitizer and illumination on the extent of photodynamic therapy
      (PDT)-induced bladder damage and recovery was investigated using a mouse model.
      The three photosensitizers studied were Photofrin, meso-tetrahydroxyphenylchlorin
      (m-THPC) and bacteriochlorin a (BCA). Functional bladder damage was
      quantitatively assessed from increases in urination frequency index (FI) at 1-35
      weeks after illumination and histological damage was qualitatively assessed at 1
      day, 1, 2 and 12 weeks. Photofrin-mediated PDT caused an acute increase in FI at
      1 week, with recovery within 2-8 weeks after light doses of 2.7-8.2 J/cm2. After
      higher light doses there was only partial recovery. Previous results indicated
      that the acute response and rate of recovery was the same whether Photofrin was
      given at 1 day or up to 7 days before illumination. The m-THPC-mediated PDT at
      drug doses of > or = 0.3 mg/kg also resulted in a marked acute response with good
      recovery, even after 10.8 J/cm2. Lower drug doses in combination with 5.4 J/cm2
      did not result in acute or late damage. There was no significant difference in
      acute response when m-THPC was given 1, 3 or 7 days before illumination, although
      recovery was faster for the longer illumination intervals (3 or 7 days).
      Illumination at 1 h after 20 mg/kg BCA induced an acute response within 2 days
      after illumination, with recovery within 4-8 weeks. Lower drug doses did not
      result in damage. The most prominent histological changes during the acute period
      with all three photosensitizers were submucosal edema and vessel dilation, with
      epithelial denudation (depending on drug/light dose). We conclude that BCA and m
      THPC are both potent new photosensitizers. They can induce a moderate to severe
      acute bladder response with complete healing over a period of a few weeks. The
      photosensitizer m-THPC is very effective with low doses of photosensitizer and
      light, whereas relatively high doses of BCA and light are required to obtain
      equivalent functional bladder damage in our mouse model.

PMID- 8881338
TI  - The protective effect of N-acetylcysteine on UVB-induced immunosuppression by
      inhibition of the action of cis-urocanic acid.
AB  - A recent study has shown that N-acetylcysteine (NAC) not only has sun-protective
      properties but also inhibits the UVB-induced suppression of contact
      hypersensitivity (CHS) in mice. Because NAC does not absorb any UVA (320-400 nm
      radiation) or UVB (290-320 nm radiation) we have studied the underlying mechanism
      of protection. Irradiation of solutions of plasmid DNA with UVC (200-290 nm
      radiation) (10 J m-2) resulted in the formation of cyclobutane pyrimidine dimers,
      but the extent to which this occurred was not affected by the presence of NAC as
      was determined by an in vitro T4 endonuclease assay. N-acetylcysteine proved not
      to have any effect on the photoisomerization of trans-urocanic acid (UCA) to its
      cis-form in vitro; at equilibrium, approximately 55% cis-UCA was formed. The same
      percentage was also found in vivo on exposure of mice to UVB (15 kJ m-2). Topical
      application of NAC 30 min prior to irradiation did not have any influence as well
      on the photoisomerization of trans- to cis-UCA. These in vivo experiments were
      performed under the same conditions used previously to show the protective effect
      of NAC against UVB-induced suppression of CHS. We conclude that this protection
      of NAC is at least partly based on interference in the role of cis-UCA in UVB
      induced suppression of CHS. This conclusion is supported by the observation that
      NAC completely inhibits the suppression of CHS by cis-UCA administered to mice
      that were always kept in the dark. In the same range of doses as used in the
      present study, it was shown in our previous study that NAC alone does not affect
      the CHS response.

PMID- 8881339
TI  - Photolysis of retinol in liposomes and its protection with tocopherol and
      oxybenzone.
AB  - In this work the stabilities of retinol in methanolic solutions and liposomal
      suspensions exposed to UV light were compared using absorbance spectroscopy and
      the ability of alpha-tocopherol and the sunscreen additive, oxybenzone, to reduce
      the rate of retinol decomposition assessed. Retinol in methanol decolorized
      almost completely within a few minutes of exposure to a 6 W 350 nm wavelength
      lamp. From the concentration dependence of the reaction rates it appears that
      retinol activated by light can decomposed either directly or after collision with
      a second retinol molecule. Several reaction products are formed. alpha-Tocopherol
      solutions were unaffected by 350 nm light but they did darken when irradiated
      with 250 nm wavelength light. Addition of alpha-tocopherol or removal of oxygen
      from the retinol in methanol solutions reduced only slightly the rates of retinol
      photolysis. When dispersed in water within liposomes made of equimolar egg
      phosphatidylcholine (PC) and cholesterol, up to six-fold increases in the
      decomposition rate of the retinol were observed. The reaction rate could be
      reduced but only slightly by increasing the ratio of PC to retinol. A mechanism
      that explains the concentration dependence of the retinol photolysis is that the
      reduction in reaction rate on diluting the retinol concentration within a given
      liposome was due to the prevention of the reaction between one light-activated
      retinol molecule with another within the same liposome. Incorporation of
      oxybenzone into the liposomes reduced the reaction rates. The results suggested
      that most of the protection in this case arises through the oxybenzone closet to
      the light source absorbing the light, thereby preventing it reaching retinol much
      further into the sample. Incorporation of alpha-tocopherol into the liposomes
      could also reduce substantially the photolysis rate of co-entrapped retinol. The
      mechanism of protection in this case appears to be via the tocopherol quenching
      activated retinol molecules. The close proximity of the tocopherol to the retinol
      within a single liposome has shown to be important in this case. Only slight
      protection of retinol in one liposome by tocopherol in another was observed under
      the conditions studied. This means that the protection by tocopherol will still
      be observed if the liposome dispersions are diluted considerably or if only thin
      samples are exposed to light.

PMID- 8881340
TI  - Using a choice assessment to predict reinforcer effectiveness.
AB  - A choice assessment has been found to be a more accurate method of identifying
      preferences than is single-item presentation. However, it is not clear whether
      the effectiveness of reinforcement varies positively with the degree of
      preference (i.e., whether the relative preference based on the results of a
      choice assessment predicts relative reinforcer effectiveness). In the current
      study, we attempted to address this question by categorizing stimuli as high,
      middle, and low preference based on the results of a choice assessment, and then
      comparing the reinforcing effectiveness of these stimuli using a concurrent
      operants paradigm. High-preference stimuli consistently functioned as reinforcers
      for all 4 clients. Middle-preference stimuli functioned as reinforcers for 2
      clients, but only when compared with low-preference stimuli. Low-preference
      stimuli did not function as reinforcers when compared to high- and middle
      preference stimuli. These results suggest that a choice assessment can be used to
      predict the relative reinforcing value of various stimuli, which, in turn, may
      help to improve programs for clients with severe to profound disabilities.

PMID- 8881341
TI  - Effects of problem difficulty and reinforcer quality on time allocated to
      concurrent arithmetic problems.
AB  - Students with learning difficulties participated in two studies that analyzed the
      effects of problem difficulty and reinforcer quality upon time allocated to two
      sets of arithmetic problems reinforced according to a concurrent variable
      interval 30-s variable-interval 120-s schedule. In Study 1, high- and low
      difficulty arithmetic problems were systematically combined with rich and lean
      concurrent schedules (nickels used as reinforcers) across conditions using a
      single-subject design. The pairing of the high-difficulty problems with the
      richer schedule failed to offset time allocated to that alternative. Study 2
      investigated the interactive effects of problem difficulty and reinforcer quality
      (nickels vs. program money) upon time allocation to arithmetic problems
      maintained by the concurrent schedules of reinforcement. Unlike problem
      difficulty, the pairing of the lesser quality reinforcer (program money) with the
      richer schedule reduced the time allocated to that alternative. The magnitude of
      this effect was greatest when combined with the low-difficulty problems. These
      studies have important implications for a matching law analysis of asymmetrical
      reinforcement variables that influence time allocation.

PMID- 8881342
TI  - Teaching computer-based spelling to individuals with developmental and hearing
      disabilities: transfer of stimulus control to writing tasks.
AB  - Computer-based instruction may yield widely useful handwritten spelling.
      Illustrative cases involved individuals with mental retardation and hearing
      impairments. The participant in Study 1 matched computer pictures and printed
      words to one another but did not spell the words to pictures. Spelling was then
      taught using a computerized procedure. In general, increases in the accuracy of
      computer spelling were accompanied by improvements in written spelling to
      pictures. Study 2 extended these results with a 2nd participant. After initial
      training, spelling improved in the context of a retrieval task in which the
      participant (a) wrote a list of the names of objects displayed on a table, (b)
      selected the objects from a shelf, and (c) returned the objects to the table.
      Nearly perfect accuracy scores declined on some retrieval trials conducted
      without a list, suggesting that the list may have served a mediating function
      during retrieval. Transfer of stimulus control of computer-based teaching to the
      retrieval task may have been attributable to the existence of stimulus classes
      involving pictures, objects, and printed words.

PMID- 8881343
TI  - Combining noncontingent reinforcement and differential reinforcement schedules as
      treatment for aberrant behavior.
AB  - Research has shown that noncontingent reinforcement (NCR) can be an effective
      behavior-reduction procedure when based on a functional analysis. The effects of
      NCR may be a result of elimination of the contingency between aberrant behavior
      and reinforcing consequences (extinction) or frequent and free access to
      reinforcers that may reduce the participant's motivation to engage in aberrant
      behaviors or mands. If motivation is momentarily reduced, behavior such as mands
      may not be sensitive to positive reinforcement. In this study, for 3 children
      with aberrant behavior maintained by tangible positive reinforcement,
      differential-reinforcement-of-alternative-behavior schedules were superimposed on
      NCR schedules to determine if mands could be strengthened. Results for the
      participants indicated that NCR did not preclude reinforcement of mands.

PMID- 8881344
TI  - Peer modeling of response chains: observational learning by students with
      disabilities.
AB  - Peer models (classmates without disabilities) who were proficient in performing a
      task completed one response chain each day and described the steps they performed
      while their classmates with disabilities observed. Three students with
      disabilities participated, and their performance of the response chains was
      assessed immediately prior to and following the peer modeling each day. A
      multiple probe design across response chains, replicated across children with
      disabilities, was used. In addition, participation and social interactions of
      children with disabilities and their peer models were assessed in classroom
      activities after daily modeling sessions. The results indicate that the peer
      models performed the response chains accurately and quickly, and students with
      disabilities acquired the response chains. Across the study, participation in
      classroom activities was high, social interactions were low, and neither was
      affected by the peer modeling intervention.

PMID- 8881345
TI  - Defining, validating, and increasing indices of happiness among people with
      profound multiple disabilities.
AB  - In this study we attempted to operationalize, measure, and increase happiness
      among people with profound disabilities. Happiness indices were defined and
      observed among 5 individuals. Validation measures indicated that (a) increases in
      happiness indices were observed when individuals were presented with most
      preferred stimuli relative to least preferred stimuli, (b) increases in
      unhappiness indices were observed when they were presented with least preferred
      relative to most preferred stimuli, and (c) practitioner ratings of participant
      happiness coincided with observed indices. Subsequently, classroom staff
      increased happiness indices through presentation and contingent withdrawal of
      activities. Results suggested that a behavioral approach can enhance happiness as
      one aspect of quality of life among people with profound disabilities. Research
      directions are offered that focus on using a behavioral approach to investigate
      other private events that are important among people with disabilities.

PMID- 8881346
TI  - The effects of meal schedule and quantity on problematic behavior.
AB  - We present 2 case examples that illustrate the effects of meal schedule and
      quantity on displays of problematic behavior. In the first example, self-injury
      displayed by a toddler with severe developmental delays was maintained by parent
      attention, but only when he was satiated for food. When he was food deprived,
      self-injury decreased but did not appear to be differentiated across low or high
      social conditions. In the second example, crying and self-injury displayed by an
      elementary-aged girl with severe disabilities were correlated: Both behaviors
      were associated with food quantity, and neither behavior was responsive to social
      stimuli. These results replicate and extend previous findings demonstrating that
      meal schedule or food quantity can affect problematic behavior. In the present
      studies, brief functional analyses of aberrant behavior provided useful
      information for interpreting distinct patterns of behavior displayed by each
      child. We discuss these results in terms of the concept of establishing
      operations.

PMID- 8881347
TI  - On the function of self-restraint and its relationship to self-injury.

PMID- 8881348
TI  - Self-restraint as positive reinforcement for self-injurious behavior.
AB  - Many individuals who engage in self-injurious behavior (SIB) also exhibit self
      restraint. We compared rates of SIB exhibited by a 32-year-old woman diagnosed
      with profound retardation across conditions in which access to restraint was (a)
      continuously available, (b) presented as a consequence for SIB, or (c)
      unavailable. Rates of SIB increased when access to restraint was contingent upon
      SIB and decreased when restraint was unavailable, suggesting that self-restraint
      functioned as positive reinforcement for SIB.

PMID- 8881349
TI  - Further analysis of the relationship between self-injury and self-restraint.
AB  - It has been suggested that self-restraint, a phenomenon often correlated with
      self-injurious behavior (SIB), may be maintained by negative reinforcement in the
      form of escape from the aversive properties of SIB (e.g., pain). We examined the
      effects of blocking SIB (and presumably removing any aversive effects) on the
      self-restraint of a 19-year-old male with severe mental retardation. Consistent
      with the negative reinforcement hypothesis, blocking SIB resulted in near-zero
      levels of SIB and moderate reductions in self-restraint.

PMID- 8881350
TI  - The effects of contingent and noncontingent attention on self-injury and self
      restraint.
AB  - Self-restraint and self-injurious behavior (SIB) are two responses that can
      sometimes be members of the same functional response class (i.e., maintained by
      the same contingency). In such cases, a single treatment should be effective for
      both responses. In this investigation, we examined the effects of providing
      attention (the presumed reinforcer) both noncontingently and contingent upon
      either SIB or self-restraint. Results were consistent with our hypothesis that
      both responses were maintained by attention and suggested that noncontingent
      reinforcement was a potentially effective treatment.

PMID- 8881351
TI  - Use of a token economy to increase compliance during hemodialysis.
AB  - We report the effects of using a token economy to treat noncompliant behavior in
      a 10-year-old male hemodialysis patient. The results of an ABAB design indicated
      that the intervention increased compliant behavior during both treatment phases
      and that compliance was maintained at 3- and 6-month follow-up observations.

PMID- 8881352
TI  - Effects of equal and unequal reinforcer duration during functional analysis.
AB  - In the functional analysis described by Iwata, Dorsey, Slifer, Bauman, and
      Richman (1982/1994), reinforcer duration varied across conditions (e.g., brief
      attention vs. 30 s of escape); this may result in unequal exposure to the
      establishing operations for aberrant behavior. In this study, we compared the
      effects of unequal and equal reinforcer duration during a functional analysis.
      The results showed that reinforcer duration affects the rate of aberrant behavior
      and may potentially alter functional analysis interpretation.

PMID- 8881353
TI  - A prompt plus delayed contingency procedure for reducing bathroom graffiti.
AB  - This study assessed the effectiveness of posting signs for reducing graffiti in
      three men's restrooms on a college campus using a multiple baseline across
      settings design. During baseline, graffiti increased almost daily in each of the
      three settings. Immediately following the intervention, no marks were made on any
      of the three walls. Results were maintained at 3-month follow-up. A possible
      explanation for the results is that the signs specified an altruistic
      contingency.

PMID- 8881354
TI  - Comparison of prototype and rote instruction of English names for Chinese visual
      characters.
AB  - This study compared prototype and rote instruction of English names for Chinese
      visual characters. In the prototype condition, participants were taught the
      meaning of the prototype that served as the distinctive feature of multicomponent
      characters. In the rote condition, participants traced the character and wrote
      its translation. Participants learned more rapidly and maintained more words in
      the prototype condition.

PMID- 8881355
TI  - Functional analysis and treatment of eye poking with response blocking.
AB  - A functional analysis of eye poking by a 4-year-old female with severe
      disabilities and visual impairments showed that high rates occurred in all
      conditions. We conducted a series of probes to identify the maintaining variable
      for eye poking following an undifferentiated functional analysis. Results showed
      that eye poking decreased only when we interrupted finger-eye contact by blocking
      the response.

PMID- 8881356
TI  - Sleep deprivation, allergy symptoms, and negatively reinforced problem behavior.
AB  - We studied the relation between the presence versus the absence of sleep
      deprivation or allergy symptoms and the rate and function of problem behavior.
      Three students whose problem behavior was negatively reinforced by escape form
      instruction were studied across several weeks using analogue functional analyses.
      Our results indicated that the extraexperimental events were associated with (a)
      termination of instruction functioning as a negative reinforcer, (b) increased
      rates of negatively reinforced problem behavior, or (c) increased rates of
      problem behavior across all conditions.

PMID- 8881357
TI  - [Recent data on hepatic lipase gene. Structure and functions of this enzyme].
AB  - Hepatic lipase (HL) is almost exclusively synthesized in the liver. Its gene is
      located on chromosome 15 in man, on chromosome 9 in rat, and has 9 exons and 8
      introns. Inhibitory and activator sequences have been found at the 5' end of the
      gene, upstream to the initiation site, as well as several consensus sequences
      such as TRE, SRE, AP-2, CEBP, ERE, AF1 and OCT-1. Glycosylation is an essential
      step for full active mature protein. The catalytic site is in the N-terminal part
      of the lipase gene while the lipid binding site is at its C-terminal end. HL is
      generally thought to be active as a dimer. This enzyme hydrolyses the acyl ester
      bonds of glycerides and phospholipids as well as the acyl CoA-thiol ester bonds.
      After being secreted by the hepatocytes, HL remains on the surface of hepatic
      endothelial cells and hepatocytes, bound to heparan sulfate proteoglycans, where
      it acts on the uptake of chylomicron remnants, IDL and HDL cholesterol ester. HL
      also participates in the VLDL to IDL and LDL cascade and in the conversion of
      HDL2 to HDL3 and pre-beta 1 HDL. Thus, HL plays an important role in lipoprotein
      metabolism and in reverse cholesterol transport and may thus be involved in
      atherogenic processes. Moreover, HL expression is regulated by hormones and
      nutritional state in the pre- and post-natal periods. Therefore, it appears of
      interest to gain further insight into the regulation of HL gene expression in
      order to better understand plasma lipoprotein metabolism.

PMID- 8881358
TI  - [Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor
      receptor in breast cancer: correlation with clinical and biological parameters].
AB  - Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth
      factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated.
      Correlations between these assays and some clinical and biological parameters
      were also studied. The repeatability and reproducibility of standard curves for
      the two methods gave a coefficient of variation (CV) of less than 4% and about
      10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was
      examined by using dilution and recovery tests throughout the standard curves. The
      linear relations between theoretical and measured values, for these tests, had
      slopes close to 1 and an intercept near 0. The median value for EGF-R, measured
      on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein,
      the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median
      value, measured using the same population, was 2.75 human neu unit/micrograms
      protein, the mean value was 7.85 (range 1 to 125). There was an inverse
      relationship between EGF-R values and those for the estrogen receptor (ER),
      progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2
      oncoprotein concentrations were positively correlated with ER, pS2 protein and
      cathepsin D. Furthermore, a significant positive correlation was observed between
      EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic
      assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable.
      The accurate standardisation of immunoenzymatic assays could contribute to the
      clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast
      cancer.

PMID- 8881359
TI  - [Contribution of cytology and lymphocyte phenotyping in the biological diagnosis
      in infectious mononucleosis due to Epstein-Barr virus].
AB  - Because infectious mononucleosis is characterized by a T cell proliferation
      reacting with EBV-infected lymphocytes, we studied the changes in the blood cell
      counts and in the immunophenotype of the lymphocytes during this infection. The
      laboratory findings were similar for the different age groups, except in children
      less than 5 years old in whom we found a significantly less intense CD8+ S6F1+
      response. According to this study, virus-specific serodiagnostic tests rarely
      show evidence of an acute primary EBV infection if the peripheral blood analysis
      fails to reveal significant changes in the leucocyte counts and in the T
      lymphocyte profiles. The study of this hematologic picture is a useful tool for
      the confirmation of infectious mononucleosis; moreover, it could greatly help
      when diagnostic problems occur.

PMID- 8881360
TI  - [Evaluation of CK-MB determination technique by immuno-enzymolfluorometry with
      Vidas (bioMerieux)].
AB  - The aim of this study was to evaluate a new automated fluorimetric enzyme
      immunoassay for CK-MB using the Vidas bioMerieux. The results for sera from 222
      patients were compared with those obtained using two other methods of CK-MB
      determination in mass units (Stratus II Dade, Magic Lite Analyzer II Ciba
      Corning). Satisfactory results were obtained for within-run precision (CV < 9%)
      and between-run precision (CV < 10%) with medium (20 micrograms.L-1) and high
      (100 micrograms.L-1) concentrations of control sera. The method was linear in the
      range 1.7 micrograms.L-1 to 235 micrograms.L-1. Comparison with the two other
      techniques led to the following regression equations: y (Vidas) = 0.512 + 1.319 x
      (Stratus) [r = 0.991] and y (Vidas) = -0.15 + 0.795 x (Magic Lite) [r = 0.958].
      The results obtained are highly correlated (p < 0.0001). The reference values
      were established on sera from healthy donors (n = 77). The Vidas technique gave
      analytical and clinical results similar to those of the other immunoenzymatic
      methods of CK-MB determination.

PMID- 8881362
TI  - Comparative evaluation of blood culture using the Vital automated system and the
      Becton-Dickinson Septi-Chek BHI-S biphasic and Sch bottles.
AB  - A comparative study was performed using 1,168 aerobic and anaerobic blood culture
      pairs from 395 patients, during which 5-10 mL of blood were collected in both
      Septi-Chek BHI-S biphasic and Septi-Chek Sch bottles (Becton-Dickinson, Meylan,
      France) and Vital AER and Vital Ana bottles (bioMerieux, Marcy-l'Etoile, France).
      The bottles were analyzed by using a 7-day protocol for Vital and a 12-day
      protocol for Septi-Chek. The Vital bottles revealed negative were all subcultured
      at the end of the protocol. Of the 374 positive Septi-Chek bottles, only 202
      bottles gave a positive subculture. Of the 245 positive Vital bottles, 223
      bottles led to the isolation of a microorganism. Thirty-five septic episodes were
      detected by Septi-Chek compared to 38 by the Vital system (only clinically
      significant isolates were taken into consideration). Four septic episodes were
      detected by Vital only (one episode implicating coagulase-negative
      Staphylococcus, one Streptococcus pneumoniae, one Pseudomonas aeruginosa and one
      Candida albicans, involving a total of 15 bottles). One septic episode
      implicating Bacteroides fragilis was detected by Septi-Chek only (five bottles).
      Among the negative Vital bottles, only six bottles gave a positive terminal
      subculture. This study validates the reliability of the Vital system to detect
      positive blood cultures.

PMID- 8881361
TI  - [Multicenter evaluation of thr Abbott glycosylated hemoglobin assay on IMx].
AB  - The Abbott IMx glycated hemoglobin assay was evaluated in a multicentre study.
      This method utilizes boronate affinity chromatography, and ion-capture
      technology. This assay determines both total glycohemoglobin (% GHb) and
      percentage of hemoglobin Alc (% HbAlc). The precision of the assay was evaluated:
      the intra-assay and interassay coefficients of variation were judged to be
      satisfactory (< 6.5%). We determined the accuracy of the assay by comparison with
      a reference HPLC assay for 603 specimens; coefficients of correlation were
      between 0.88 and 0.96. We studied the interference of bilirubin and glucose and
      found no interference at usual concentrations. The presence of abnormal
      hemoglobins (HbF and some Hb structural variants HbS, HbC) was not detected with
      the Abbott IMx assay; however, this assay showed no significant interference from
      the hemoglobin variants tested for heterozygous hemoglobinopathies (percentage of
      abnormal hemoglobin < 60%). We also determined normal values for HbAlc with this
      technology (164 specimens): 4.1 to 6.1%.

PMID- 8881363
TI  - Congenital toxoplasmosis: specific IgM in fetal blood, cord blood and in the
      newborn.

PMID- 8881364
TI  - Lactose-fermenting Salmonella typhi strain isolated from patient with typhoid
      fever.

PMID- 8881365
TI  - [Incidence of the standardization of serum transferrin assay by CRM 470 on iron
      saturation ratio of transferrin].

PMID- 8881366
TI  - The last revised "Euro-American classification" of lymphoid leukemias and non
      Hodgkin's lymphomas: the same inaccuracies and inconsistencies in a chaotic
      complexity.
AB  - After a review of the recent physiologic, cellular genetic and molecular genetic
      acquisitions, a critical comment of the proposed classification is presented
      concerning especially a) the inclusion in the so-called "precursor B
      lymphoblastic leukemias", which are pre-B neoplasias, of Burkitt's leukemic
      lymphoma, the cells of which are sIg+, hence B and not pre B; b) the inclusion in
      the chronic B lymphocytic leukemia of the so-called Galton's "prolymphocytic"
      leukemia, the cells of which are also sIg+, thus B and not pro B. In fact, the
      transformed blastoid medium size cells of this leukemia present the markers of
      the plasmablasts, which are the precursors of the long-lived plasma cells and
      migrate from the lymphoid tissue T-zone to bone marrow, where they secrete IgD,
      or G, or E, or to the mucosae, where they secrete IgA. Thus the so called "B
      prolymphocytic leukemia" is the leukemic conversion of the (blastoid medium size
      cell) plasmablast lymphoma. There is in the new classification, a "large cell
      lymphoma" entity, which makes redundance with the "large cell follicle centre
      lymphoma". This large cell lymphoma representes a heterogen complex, as it
      includes the B-immunoblastic lymphoma which is not presented as an entity. As far
      as T lymphomas are concerned, it is not indicated that the CD8 cells may be CD57
      + or - , and CD28 + or -. It could be mentioned that the cytotoxic T-cells are
      CD8+ C57- CD28+, while the suppressor T-cells are CD8+ CD57+ CD28-.

PMID- 8881367
TI  - Bone marrow transplantation in chronic lymphocytic leukemia and lymphomas.
AB  - Until recently younger patients with B-cell chronic lymphocytic leukemia (CLL)
      have not been considered for treatment with high-dose therapy and bone marrow
      transplantation (BMT). Current results show that both autologous and allogeneic
      bone marrow transplantation can induce a high percentage of long lasting
      remissions in younger patients with poor-risk CLL. Because of the investigational
      character of BMT for CLL, all eligible patients should be enrolled in clinical
      trials. Autologous BMT or peripheral blood stem cell transplantation (PSCT) have
      become standard therapies for relapsed patients with Hodgkin's disease (HD) or
      intermediate- and high-grade non-Hodgkin's lymphoma (NHL). Data on autologous
      transplantation for low-grade NHL are not mature enough and more experience is
      needed in order to assess the long-term value of such approach. Ongoing studies
      of high-dose therapy in lymphomas are focused on performing BMT earlier in the
      course of the disease and exploring alternative sources of hematopoietic rescue
      such as allogeneic stem cell transplantation.

PMID- 8881368
TI  - Role of natural effector cells in the prevention of radiation-induced
      leukemogenesis.
AB  - Four once-weekly exposures of 225 rads (R) of whole body X-irradiation causes a
      high incidence of lymphoma in C57BL/6 (C57) mice. The role of natural effector
      cells in radiation-induced leukemogenesis was investigated. Activity of natural
      killer (NK) and natural cytotoxic (NC) cells was depressed in irradiated mice
      over a prolonged period. Transplantation of bone marrow (BM) cells from normal
      C57 mice to irradiated mice restored their NK responses and prevented development
      of lymphoma. The effect of beige BM cell transfer to irradiated mice was not
      clear. Unlike short-term (4-hour) assay, results of long-term (20-hour) assay
      suggest partial restoration of NK and full restoration of NC activity in
      irradiated mice. Treatment of irradiated mice with polyinosinic: polycytidillic
      acid (poly I:C) increased NK activity and lymphoma resistance. Administration of
      small repeated doses of poly I:C to irradiated mice significantly prevented the
      development of lymphoma as well as significantly prolonging overall survival time
      in irradiated mice. These observations indicate that natural effector cells
      mediate resistance to radiation-induced leukemogenesis.

PMID- 8881369
TI  - Improved therapy for children with acute lymphoblastic leukemia.
AB  - We have examined the factors influencing clinical prognosis in Japanese children
      with B-precursor acute lymphoblastic leukemia (ALL), who have been treated in
      consecutive chemotherapeutic trials from 1976 to 1995. During this time the
      results of treatment have steadily improved in children with average presenting
      features (age 1-10 years old and leukocyte counts > 50,000/microL). The 4-year
      event-free survival (EFS) estimates now exceed 85% in our current trials.
      Furthermore, high-dose methotrexate and intrathecal therapy could be substituted
      for cranial irradiation without an increase of central nervous system relapse
      rate. However, children with unfavorable presenting features (leukocyte counts >
      or = 50,000/microL; high-risk group) have a worse prognosis, although there is
      some improvement of outcome. The patients in the high-risk group have obtained
      the 4-year EFS rate of better than 60%. Further investigations of prognostic
      factors in ALL focused on the biological features may permit identification of
      groups of children at risk of very poor outcome. In the patient cohorts
      consistently resistant to chemotherapy, the hazards of more intensive treatment
      such as bone marrow transplantation may be outweighed by the possible benefits.

PMID- 8881370
TI  - The role of interferon in the therapy of malignant lymphoma.
AB  - As a single agent, interferon-alpha (IFN-alpha) can induce remissions, mostly
      partial, in a large fraction of patients with indolent lymphomas, including the
      low grade B-cell lymphomas and cutaneous T-cell lymphoma. In aggressive
      lymphomas, IFN has minimal activity, and in Hodgkin's disease the limited
      available experience suggests only modest activity. In indolent B-cell lymphomas,
      IFN has been integrated with chemotherapy in several large trials: the majority
      of these trials indicate a favorable impact on failure-free survival; a survival
      benefit of IFN has been reported by the French-Belgian group. Updated results are
      now available from a previously reported trial from the MD Anderson Cancer Center
      that also indicate an apparent survival benefit when IFN is used in conjunction
      with chemotherapy in patients with indolent B-cell lymphoma.

PMID- 8881371
TI  - Increased glutathione expression in cells induced by Crassostera gigas extract
      (JCOE).
AB  - The amino-acid composition of Crassostera gigas extract powder (JCOE, Japan
      clinic oyster extract) is high in glutamic acid and taurine. In order to study
      whether these components present in JCOE could be contributory factors in
      enhancing cellular glutathione-stimulating hormone (GSH) and glutathione S
      transferase (GST), HL60 cells were exposed to increasing concentrations of JCOE.
      Statistically significant increases in GSH occurred at extract concentrations of
      0.05 and 0.1% with no significant change in GST activity. Because of the high
      taurine levels measured in the extract, the effects of micromolar taurine
      supplementation of the medium were studied. A modest, but not statistically
      significant increase in both GSH levels and GST activity was measured. We
      therefore conclude that while the taurine present in JCOE could be a contributory
      factor in enhancing GSH and GST, it was not the only stimulus.

PMID- 8881372
TI  - Pharmacokinetic profile of recombination human insulin-like growth factor binding
      protein-1 in athymic mice.
AB  - Neutralization of insulin-like growth factor action by insulin-like growth factor
      binding protein-1 inhibits the in vitro growth of breast cancer cells. We
      performed this study to determine the pharmacokinetic profile of recombinant
      human IGFBP-1 (rhIGFBP-1) in athymic mice as a prelude to testing this protein in
      a human tumor xenograft model. After the subcutaneous injection of 1 mg, rhIGFBP
      1 migrating at 29 kDa could be detected by ligand blotting and immunoblotting.
      Plasma concentrations of rhIGFBP-1 were quantified by immunoassay and
      demonstrated a half-life was 2.49 hours with the maximal concentration of 43.5
      micrograms/mL occurring at 1 hour. The area under the concentration-time curve
      was 78.32 micrograms x hr/mL. Plasma clearance was 12.77 mL/hr and the mean
      residence time was 1.96 hours. rhIGFBP-1 was also detected in some tissues and
      was also cleared rapidly. These results show that high plasma and tissue levels
      of rhIGFBP-1 can be obtained after subcutaneous injection in athymic mice,
      however, the short half-life of the protein may limit its therapeutic use.

PMID- 8881373
TI  - Purine ribonucleotide content in infected HIV-RT+ and HIV-RT- lymphoblastoid cell
      lines.
AB  - We have studied the purine nucleotide metabolism in the following cell lines: a),
      H9 (continuous human T-cell line) and H9/HTLV-III (H9 cell line, infected with
      RT+ HIV-I virus); b), A3.01 (human lymphoblastoid cell line CD4+) and 8E51 (line
      A3.01 permanently transfected with RT-HIV-I virus). Purine metabolism was studied
      by evaluating the content of the most important ribonucleotides (AMP-GMP-IMP-NAD
      ADP-GDP-ATP-GTP) and their ratios. We determined several differences between the
      cell lines before and after viral infection. All nucleotides except triphosphates
      were reduced in H9/HTLV-III with respect to H9 cells; in 8E51, however,
      triphosphates were markedly reduced, while monophosphates increased with respect
      to A3.01 uninfected cells. Also the ratios exhibited different behaviors, for
      example the total adenine nucleotides total guanine nucleotides ratio (sigma
      A/sigma G) was enhanced in H9/HTLV-III cells with respect to H9 and unaltered in
      8E51 with respect to A3.01 cells. We may conclude that the HIV-I virus strongly
      influences the purine nucleotide metabolism of the host cells and that the
      changes are different when induced either by RT+ or RT- virus.

PMID- 8881374
TI  - Triazolines 26: 1-Aryl-5-amido-1,2,3-triazolines, a new group of triazoline
      anticonvulsants. Effect of 5-substitution on anticonvulsant activity.
AB  - Studies in our laboratories have led to the discovery of the delta 2-1,2,3
      triazolines as a unique family of anticonvulsant agents hitherto unknown. The
      anticonvulsant activity of 1,5-diaryl- and 1-aryl-5-pyridyltriazolines was
      previously reported; this paper describes the evaluation of two series of 1-aryl
      5-amido-1,2,3-triazolines, A and B, where the 5-amido groups are (2-oxo-1
      pyrrolidino)- (1-8) and (N-methyl-N-acetamido)- (9-15), respectively. The 1-aryl
      5-(2-oxo-1-pyrrolidino)-1,2,3-triazolines of the A series, which are uniquely
      substituted with the pyrrolidinone lactam ring, a cyclic gamma-aminobutyric acid
      (GABA) structure, seem to function by enhancing inhibitory GABAergic mechanisms.
      Radioligand binding studies for the two most active triazolines 2 and 7, indicate
      that both compounds strongly inhibit the specific binding of [3H]GABA to GABAB
      receptor sites, with Ki = 1.7 and 0.91 microM respectively. The anticonvulsant
      activity among the various groups of triazolines studied so far appears to be
      dependent on the 5-substituent groups: 4-pyridyl- >> 2-oxo-1-pyrrolidino- > N
      methyl-N-acetamido- > 3-pyridyl > or = aryl approximately 2-pyridyl > 2-quinolyl.

PMID- 8881375
TI  - An 'antigenic ligand competition' model for antigen receptor-mediated lymphocyte
      selection.
AB  - The 'antigenic ligand competition' model advanced herein represents a principally
      novel view on lymphocyte selection, postulating a leading role in this process of
      competition between different determinants expressed on self ligands for binding
      to antigen receptors. Based on the data indicating that cell viability and cell
      growth are separately regulated processes, it is speculated that the binding of
      antigenic receptors with monovalent determinants (MDs) expressed on soluble self
      ligands may be responsible for lymphocyte survival, whereas the moderate (but not
      hyper) cross-linking of antigenic receptors with polyvalent determinants (PDs)
      expressed on other or the same self ligands may provide signalling that is
      necessary to trigger lymphocyte proliferation. In the light of the model, the
      lymphocytes whose receptors bind with high affinity to self MDs survive, while
      not receiving a proliferative stimulus. On the other hand, those lymphocytes
      whose receptors interact with high affinity with self PDs and consequently
      undergo hypercross-linking die by apoptosis. Lastly, those lymphocytes whose
      receptors interact simultaneously with both MDs and PDs in a balanced competitive
      manner receive both viability and a proliferative stimulus and, as a consequence,
      it is only they which obtain selective advantage. The balanced competition
      between self MDs and self PDs for receptor binding seems likely when the
      receptors have relatively low affinity to such determinants inasmuch as the
      opposite, namely comparably high specificity (affinity) to structurally distinct
      determinants, is unlikely. Essentially, the model presented herein also suggests
      that a balance between distinct antigenic determinants occupying antigen
      receptors may determine not only self antigen-driven lymphocyte selection, but
      also immune reactivity of the functionally mature B- and T-cells which have
      passed through this selection.

PMID- 8881376
TI  - [Individual dose adjustment in anticancer chemotherapy].

PMID- 8881377
TI  - [Measurement of energy expenditure at rest in nutritional disorders. Study in 229
      patients].
AB  - Resting energy expenditure was measured by indirect calorimetry, and body
      composition was evaluated by electrical body impedance analysis in 229 female
      patients with anorexia nervosa, cancer, non tumoral disease, obesity, and 42
      healthy women. Results were compared with theoretical formulas based on
      anthropometry, and expressed by kilogram of body weight and lean body mass. Each
      group was compared with each other and with controls. Resting energy expenditure
      of controls is quite identical with the theoretical value; it is very low for
      anorectic patients, high for obese patients, high during non tumoral diseases,
      and higher during neoplastic diseases. Respiratory quotient shows catabolism of
      carbohydrates in anorectic patients, and lipid catabolism in other patients.
      Results are compared with literature data, and pathophysiological mechanisms and
      clinical use of the method are discussed.

PMID- 8881378
TI  - [Initial manifestations and late diagnosis in chronic atrophic polychondritis:
      apropos of a series of 15 patients].
AB  - An auricular or nasal chondritis or a saddle nose deformity are the initial
      manifestation in half of cases of relapsing polychondritis; the other initial
      manifestations are various and less evocative; polyarthritis, laryngo-tracheal
      symptoms, episcleritis which delay the diagnosis. From 15 cases of relapsing
      polychondritis, the diagnosis time from the first symptom are studied; this one
      is long, about 3 years and 6 months (from 3 months to 17 years) in 13/15 of the
      cases even if the first manifestation is typical (external chondritis). In two
      cases only, the diagnosis was established after the first attack. This late of
      diagnosis had socioeconomical impact and exposed to severe complications like
      tracheal chondritis.

PMID- 8881379
TI  - [Genetics of Alzheimer's disease].
AB  - This review reports the different genetic factors that have been identified
      either as risk factor for Alzheimer's disease (AD) or directly causing the
      disease. First are reviewed epidemiological data and biological mechanisms about
      the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for
      Alzheimer's disease. The second part describes the mutations responsible for
      early-onset autosomal dominant AD found in three different genes. The gene
      located on chromosome 21 encodes the amyloid precusor protein (APP). The
      presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively,
      encode not yet known membrane proteins.

PMID- 8881380
TI  - [Asthma caused by food allergy].
AB  - Food allergy (FA) induced asthma is less common than FA induced atopic
      dermatitis, or angioedema. The incidence reaches 8.5%. Occupational asthma due to
      the inhalation of various food proteins is increasingly described. Egg proteins
      could be peculiarly at risk. In the childhood, all the kinds of foods can be
      incriminated. In adults, FA are predominantly due to vegetal allergens, included
      in the following botanical families: rosaceae, umbelliferae, and exotic fruits.
      Bronchi are sensitized either by inhalation of food allergens or by inhalation of
      cross-reactive pneumoallergens, such as pollens, feathers, latex. The fact that
      FA might create a bronchial hyperreactivity is controversial. Bronchial
      challenges induce late-phase reactions and document the acquisition of an
      inflammatory state. The quantity of allergens gaining access to bronchi plays a
      major part in the triggering of asthma. It can be modulated by variations of
      intestinal permeability which are related to viral infections, aspirin, alcohol,
      etc. The chemical characteristics of proteins, such as hydrophobicity might
      interfere with the passage through the gut mucosa. The diagnosis is based upon
      skin tests and the detection of specific IgE, identifying the state of
      hypersensitivity. Provocation tests are mandatory to establish FA. The
      pharmacological approach of the treatment is less important than the eviction
      insofar as the specific immunotherapy is not yet currently performed.

PMID- 8881381
TI  - [Involvements of the peripheral nervous system and primary Gougerot-Sjogren
      syndrome].
AB  - Peripheral neuropathy in primary Sjogren's syndrome is common although often
      unrecognized in mild forms of this affection. They are characterized by a
      predominently sensory deficiency and can be divided in several entities, of which
      the most important are: axonal distal symmetric polyneuropathy, either of sensory
      or sensory-motor presentation, which are supposed to be consecutive to ischemia
      induced by the vasculitis of the vasa nervorum; sensory neuronopathy mimicking
      the paraneoplastic syndromes from a clinical and electrophysiological point of
      view which are supposed to be linked to neuronal degeneration secondary to a
      lymphocytic infiltration of the dorsal root and ganglia; trigeminal sensory
      neuropathy, either alone or associated with one of the previously cited forms.
      The prescribed courses of etiological treatment consisting of corticosteroids and
      immunosuppressive agents are only effective in some acute forms. Tracking down
      systematically these peripheral neuropathies in patients affected by Sjogren's
      syndrome is the best way to recognize them. Alternatively, patients with
      unexplained neuropathies should be evaluated for the presence of Sjogren's
      syndrome.

PMID- 8881382
TI  - [Epidural lipomatosis: complication of long-term corticotherapy. Apropos of 2
      cases].
AB  - Spinal epidural lipomatosis (SEL) is defined as the deposition of loose fat
      tissue in the epidural space. Two cases are reported which illustrate the main
      features of this uncommon disease. Most frequently SEL is revealed by neurologic
      manifestations such as an acute chronic spinal cord compression. Corticosteroid
      therapy and obesity are the main factors able to induce the disease. The common
      location of the SEL at the thoracic spine is explained by the physiologic
      abundance of fat and by the relative narrowness of the spinal canal at this
      level. An osteoporotic vertebral crush fracture which reduces the diameter of the
      canal frequently reveals the SEL. MRI confirms the diagnosis of SEL and shows the
      extent in the spinal canal. The treatment of SEL is difficult. The decrease or
      the stop of corticosteroid therapy has allowed the recovery in a few cases with
      chronic neurologic symptoms. The risks of a surgical procedure are important in
      these patients and the medical or surgical treatment should be discussed taking
      into account the clinical symptoms of SEL, its location and extent, and the risks
      of recurrence if corticosteroid therapy must go on.

PMID- 8881383
TI  - [Hepatocellular carcinoma in asymptomatic primary biliary cirrhosis].
AB  - Hepatocellular carcinoma is an uncommon complication of primary biliary
      cirrhosis. Hepatocellular carcinoma occurs generally in the end stage of the
      disease. We report a case of asymptomatic primary biliary cirrhosis complicated
      by a hepatocellular carcinoma in a 66 year-old man.

PMID- 8881384
TI  - [Actinomycosis and non-Hodgkin's malignant lymphoma: fortuitous association?].
AB  - Two cases of actinomycosis associated with non Hodgkin's lymphoma (NHL) are
      reported. In one case, low grade NHL was diagnosed many years after actinomycosis
      because of the persistence of abdominal lymphadenopathy in spite of antibiotic
      therapy. In the second case, hepatic metastasis were initially suspected until
      actinomycosis diagnosis was made by percutaneous liver biopsy under scanography.
      High grade NHL was diagnosed by laparotomy and liver biopsy performed 6 weeks
      after the onset of antibiotic therapy as no improvement in hepatic lesions was
      obtained. These two case reports outline the difficulties encountered in the
      diagnosis of actinomycosis and the indication of a repeat biopsy when
      actinomycosis does not respond to antimicrobial therapy because of the
      possibility of concomitant malignancy.

PMID- 8881385
TI  - [Does general paralysis still exist in non-AIDS patients?].
AB  - A 33 year-old man was twice admitted in psychiatry for a non typical depression.
      He was later hospitalized for a convulsive seizure. Then, the discovery of
      dementia, neurologic trouble, positivity of syphilitic reaction in blood and in
      cerebro-spinal fluid allowed to diagnose general paralysis. General paralysis is
      a late complication of syphilis and it has become exceptional because of efficacy
      of detection and treatment of early state of syphilis. Now, most of cases affects
      AIDS patients. Nevertheless, this case shows that realisation of syphilitic
      reaction is always justified by any dementia or any non typical depression.

PMID- 8881386
TI  - [Value of video-assisted thoracic surgery in internal medicine. Apropos of 7
      cases].
AB  - Since a few years, the medical thoracoscopy has already been used specially for
      the diagnostic and therapeutic taking up of the pleural pathology. Behind it, the
      video-assisted thoracic surgery has been improved since 1990. As a surgical
      technology, it proved its interest refering to the classical thoracotomy by
      lessening operative morbidity and mortality. The authors discuss its main
      indications about seven cases, recruted in the internal medicine service and
      operated in the thoracic surgery service of the Val-de-Grace hospital. Some of
      these indications are now admited by most of the authors: 1) diagnostic aims:
      pulmonary biopsy in case of interstitial pathology, of pulmonary peripheral under
      pleural nodule and sometimes of solid tumors of the mediastinum, specially of
      some lymph-nodes. 2) Therapeutic aims: the spontaneous pneumothorax treatment of
      the adult remains the most classical indication; the thoracic sympathectomy, the
      creation of pleuropericardial windows and the resection of benign tumors of the
      mediastinum are now well acknowledged indications.

PMID- 8881387
TI  - [Dose expression of antineoplastic drugs].
AB  - Anticancer drugs dosage are currently adjusted to body surface area. This measure
      is supposed to be the best morphometric parameter to adjust anticancer drug
      doses. However, dose adjustment to body surface area has not historically been
      rigorously demonstrated. We propose a method to objectively test this parameter
      utility. The statistical justification of drug adjustment to body surface area
      can use mathematical equations to be expressed. We can demonstrate that body
      surface area and plasmatic total clearance of a drug should be correlated to
      adjust dose anticancer drug to body surface area. When we test the hypothesis of
      body surface area and plasmatic clearance correlation for cytarabine and
      adriamycin we did not find any significant correlation. For these anticancer
      drugs, dose adjustment to body surface area increase their pharmacokinetic and
      efficiency variabilities. The concept of dose-intensity is probably the best
      justification of individual dose adjustment from plasmatic drug samples, and from
      pharmacokinetic and pharmacodynamic studies. The determination of the "maximal
      tolerable exposition" and of the "minimal effective exposition" should reduce the
      overexpression of toxic risks and avoid the ineffective underexpositions.
      However, it is difficult to precisely define these two expositions and to
      research the most relevant pharmacokinetic parameters to their measure. Area
      under curve appears to be their most appropriate expression.

PMID- 8881388
TI  - [Febrile pancytopenia].

PMID- 8881389
TI  - [Lyme neuroborreliosis of mental manifestation. Apropos of a case].

PMID- 8881390
TI  - [Cough of urinary origin: apropos of a case].

PMID- 8881391
TI  - [Convulsion caused by ofloxacin].

PMID- 8881392
TI  - [A rare cause of hematuria: heterozygote sickle trait].

PMID- 8881393
TI  - [HHV-8 viruses].

PMID- 8881394
TI  - [Imaging of digestive involvements after irradiation].
AB  - The main limiting factor of the abdominal and pelvic radiotherapy is radiation
      damage of the digestive organs. The intestinal abnormalities resulting from
      irradiation are due to damaged blood vessels and connective tissue. Radiation
      changes in the small bowel and the recto-sigmoid are frequent and often
      symptomatic. Imaging is able to detect the induced radiation damage, even the
      asymptomatic scars. It is relevant to differentiate them from tumoral recurrence.
      The lesion location within the irradiated volume is important in the evaluation
      of post-radiotherapy imaging. Computerized tomography (CT) and magnetic resonance
      imaging (MRI) detect asymptomatic lesions in the liver, spleen and pancreas. We
      insist on the CT-imaging of induced radiotherapy changes, which are of major
      importance during the follow-up of irradiated patients.

PMID- 8881395
TI  - [Radiologic aspects of endoscopic sphincterotomy complications].
AB  - Endoscopic sphincterotomy (ES) is a minimally invasive technique which is the
      standard of reference in many clinical situations (e.g distal choledocolithiasis,
      recurrent lithiasis or bile duct stenosis). Complication are rare but are often
      misdiagnosed although radiological aspects are demonstrative. The purpose of this
      study is to illustrate the patterns of the complications. Ten patients have been
      treated for the last four years in our institution for ES complications. There
      were eight cases of pancreatitis, three of which had associated perforation, one
      arterioportal fistula, and one isolated perforation. Diagnosis was reached with
      CT in all but one case. Two patients have been successfully treated with
      percutaneous treatment (one embolization with Gianturco coils, and one drainage).
      Two patients died, one of necrotizing pancreatitis and the second of decubitus
      complication. The other patient were followed with CT. We give exemples of
      different observations and discuss their follow up. The severity and extent of
      post ES pancreatitis were readily assessed by CT and response to therapy
      monitored by serial examinations. Severity of disease, evaluated according to the
      length of hospitalization, correlated well with the presence and degree of
      pancreatic necrosis. CT also highlights perforations including minimal effusions.
      In our study differential diagnosis between post ES pancreatitis and perforation
      is not significant regarding the initial conservative therapy in both situations.
      CT scan helps us to opt for a surgical decision or for a percutaneous drainage.
      It also permits to follow the evolution of the lesions. In our cases involving
      perforations, we noted a spontaneous complete resolution of gas effusion on
      control and we also observed that pancreatitis evolution was similar to standard
      pancreatitis evolution. In a life threatening post ES hemobilia, not responding
      to standard medical treatment, angiography is the diagnostic exam of choice
      before embolization which is regarded as the best initial treatment of vascular
      lesions. We conclude that CT is the exam of choice in the initial diagnosis and
      follow up post ES complications.

PMID- 8881396
TI  - [Value of ultrasonics in differential diagnosis of pseudotumor hydatid cyst of
      the liver and other solid hepatic masses (prospective study)].
AB  - A prospective study in 88 consecutive patients with solid hepatic mass was
      performed to determine the value of ultrasound in the diagnosis of pseudo-tumoral
      hydatid cyst. Ultrasonography systematically searched 5 evocative signs:
      hypoechoic spiral, peripheric hypoechoic rim surrounded by an echoic border,
      daughter cysts, hyperechoic areas with shadowing and/or enhancement of back-wall
      echos. Diagnosis of pseudo-tumoral hydatid cyst was based upon the association
      of, at least, 2 signs. The sensitivity of echography was 92.3% and the
      specificity was 98.3%. Furthermore this study allow us to propose a new, more
      accurate, definition of the hydatid spiral. However, serologic tests were found
      to be of little interest.

PMID- 8881397
TI  - [Parietal calcifications of the kidney pelvis in Corynebacterium urealyticum
      urinary infection].
AB  - Linear renal pelvis calcifications in a native kidney due to Corynebacterium
      urealyticum are described. These micro-organisms have an opportunistic behaviour
      and can be responsible for nosocomial urinary tract infection. Alkaline incrusted
      cystitis with linear vesical calcifications are considered as the most typical
      pattern. Renal pelvis may also be concerned, with parietal calcifications.

PMID- 8881398
TI  - [Subcapsular hematoma complicating acute pyelonephritis].
AB  - Spontaneous subcapsular renal hematoma is rare and essentially associated with
      malignant, or benign tumor vascular diseases, inflammatory processes. In few
      cases, no cause was detected. We observed one additional case in a diabetic
      women. She presented fever, and bilateral flank pain. Ultrasonography showed
      bilateral subcapsular hematoma. Computed tomography confirmed these findings and
      demonstrated multiple area of acute focal pyelonephritis.

PMID- 8881399
TI  - [Cyst of the lumbar posterior longitudinal ligament. An unusual cause of non
      discal sciatica].
AB  - Ganglion cyst of the longitudinal posterior ligament of the spine is a rare
      entity, only described in 11 cases. This lesion occurs in young subjects
      suffering from classical lombosciatica, and has perhaps a traumatic origin.
      Computerized tomography and MRI provide the diagnosis.

PMID- 8881400
TI  - [Subcapsular hematoma of the liver complicating hepatic fascioliasis].

PMID- 8881401
TI  - [Treatment of eyelid carcinomas of 2 cmm or less by contact radiotherapy].
AB  - PURPOSE: Analysis of a series of 50 patients treated by contact x-ray for an
      eyelid carcinoma. METHODS: From 1980 to 1991, a series of 50 patients with 52
      lesions has been included in a protocol of contact x ray for eyelid carcinoma.
      Median age: 69 years; male: 25; female: 25. Histological or cytological diagnosis
      showed: basocell carcinoma: 47; squamous cell carcinoma: 5. The site was: lower
      eyelid; 31, inner canther: 10; outer canther: 5; upper eyelid: 6. Stade was (UICC
      1987): T1 (< or = 2 cm): 44; post excision: 8. Treatment was performed on an
      ambulatory basis with the PHILIPS RT 50 x-ray contact machine (50 KV - 0.5 mm
      A1). The diameter of the localized was 10 mm: 22; 15 or 20 mm: 30. The standard
      treatment delivered 42 Gy/7 fractions/4 weeks (1 or 2 fractions of 6 Gy for
      week). RESULTS: There was no death due to cancer. A complete response was seen 2
      months after the end of treatment in 43/44 cases. A long-term local control was
      obtained in 47 patients. Loss of eyelash was seen in the irradiated area with a
      supple and no necroses of the tarsal cartilage. The irradiated skin is slightly
      depigmented. Stenoses of the lower lacrimal duct is unusual and was seen only if
      it was in the field of irradiation. No cataract was observed. The cosmetic and
      functional results appeared excellent in the large majority of patients. One
      local relapse occurred in the irradiated area and two just outside the irradiated
      area. These 3 relapses were salvaged, two by surgical excision and one by a
      subsequent irradiation. CONCLUSION: Contact x-ray is a simple technique which
      requires no hospitalization, neither general anesthesia. It gives excellent local
      control and good cosmetic results in these small eyelid carcinomas.

PMID- 8881402
TI  - [Trabeculo-intendation. A new surgical treatment of glaucoma of the aphakic eye].
AB  - INTRODUCTION: Glaucoma of the aphakic patient is often difficult to treat.
      Classical surgical management is limited by poor quality conjunctiva and by the
      presence of the vitreous gel opposite the fistula. We present a new surgical
      technique which uses a portion of the trabeculum as a drain placed in the
      anterior chamber. MATERIAL AND METHODS: Thirty eyes (19 aphakic and 11
      pseudophakic) in 28 patients presenting refractory glaucoma were operated on by
      the same surgeon. Sixteen eyes had already undergone glaucoma surgery, 17
      presented vitreous in the anterior chamber. Average post-operative follow-up was
      18 months. RESULTS: Eighteen eyes (60%) needed no further treatment, 6 eyes (20%)
      were stabilized with a local treatment, 6 eyes (20%) remained hypertonic.
      CONCLUSION: This new surgical technique, which uses a portion of the trabeculum
      as a drain, allows for long lasting filtration in the aphakic or pseudophakic
      patient with refractory glaucoma.

PMID- 8881403
TI  - [Primary congenital ectropion. Apropos of 2 cases].
AB  - PURPOSE: Congenital lid ectropion is a rare anomaly. In the usual classification,
      primary ectropion caused by tightening of the anterior lamella may sometimes be
      confused with secondary ectropion, especially with blepharophimosis syndrome or
      euryblepharon. METHODS: Through analysis of two representative cases of
      congenital ectropion and review of literature we discuss similarities and
      differences between primary and secondary ectropion including blepharophimosis
      and euryblepharon. RESULTS: Horizontal narrowing of palpebral fissure and
      inversus epicanthal folds are the main clinical feature to be considered when
      differential diagnosis is difficult between primary forms and blepharophimosis,
      as ptosis is often an underlying abnormaly in both cases. CONCLUSION: To be
      effective, the surgical management of congenital lid ectropion requires precise
      clinical examination, clear understanding of causative factors and several
      procedures.

PMID- 8881404
TI  - [Sensitivity of the retinal pigment epithelium to spindle poisons].
AB  - PURPOSE: The function of RPE is well known in PVR. Pharmacological agents have
      been extensively studied both experimentally and clinically. Few reports have
      detailed the interactions of antimitotic drugs on the microtubule network. The
      aim of this study is to visualize by indirect immunofluorescence the effects of
      colchicine and paclitaxel on the microtubule network of cultured pig RPE cells in
      interphase. METHODS: Pigs were killed at the slaughter-house, their eyes were
      enucleated. RPE cells were isolated and cultured. RPE cells were plated onto
      glass cover-slips at a density of 2,000,000 cells/ml, cultured and treated with
      the drugs during 4 and 24 hours at 37 degrees C at different concentrations.
      Immunofluorescence reaction was developped using antitubulin and fluoresceinated
      anti-mouse antibodies. The cytoskeletons were visualized employing a Zeiss
      photomicroscope equipped with epiilumination, a 63 x lens and appropriate filters
      for fluoresceine. RESULTS: The cytoplasmic microtubules of RPE cells were
      disrupted in a concentration and time-dependant manner by colchicine. Between 10
      and 100 nm Veveral degrees of depolymarization of the microtubule network were
      observed. Paclitaxel between 1 micron and 10 microns was found to induce several
      degrees of microtubule "bundling" after 4 and 24 hours of incubation. Actin
      network was modified neither by colchicine and paclitaxel used in the same
      conditions. CONCLUSIONS: The results show that low doses of antimitotic drugs
      inhibit the microtubule network formation by depolymerization (colchicine) or
      stabilize it (paclitaxel). These actions inhibit cell division, which is one of
      the mechanisms implicated in PVR.

PMID- 8881405
TI  - [Retinal detachment and posterior lens luxation. Value of liquid
      perfluorocarbons].
AB  - PURPOSE: The purpose of this study is to review the benefits of perfluorocarbon
      liquids in the surgical treatment of retinal detachment with posterior lens
      dislocation. METHODS: Three cases of retinal detachment occurring in the presence
      of a posteriorly dislocated intraocular lens were managed with vitrectomy, fluid
      perfluorocarbon, scleral buckling and silicone oil injection. The dislocated lens
      were removed by anterior approach. RESULTS: In all cases a successful retinal
      reattachment was obtained after one or two surgical procedures.

PMID- 8881406
TI  - [Role of arterial blood pressure in the development of glaucomatous lesions].
AB  - PURPOSE: In a significant number of glaucoma patients, progression of visual
      field loss occurs despite adequate intraocular pressure (IOP) control. Other
      factors, mainly vascular, seem to play a role in the pathogenesis of these
      glaucomas. The purpose of this study was to investigate the role of blood
      pressure (BP) as one of the vascular risk factors for progression of glaucomatous
      damage. METHODS: Eighty-three glaucoma patients were categorizated as to whether
      their visual field defect were stable or progressive in the face of clinically
      stable IOP; all patients were followed for at least two years. The mean systolic
      and diastolic BP were determined, using a 24-hour ambulatory recording device,
      during diurnal (6 am-10 pm) and nocturnal (10 pm-6 am) periods. For each patient,
      the nocturnal systolic and diastolic dips, and the BP variability (i.e. standart
      deviation, and percentage decrease from maximal to minimal readings) were
      determined. RESULTS: Forty-three patients had stable visual fields (25 females,
      58.9 years old +/- 6.88; 18 males, 58.6 years old +/- 11), while 40 patients
      showed progressive visual field loss (23 females, 67.4 years old +/- 9.98; 17
      males, 64.5 years old +/- 9.44). In the progressive group, women were older (p =
      0.017), systolic (p = 0.0375) and diastolic (p = 0.0083) dips were greater, as
      also BP variability: systolic standard deviation was greater (p = 0.027) as
      percentage decrease from maximal systolic readings (p = 0.034). There were no
      difference for systolic, diastolic, diurnal or nocturnal mean BP in these two
      groups. CONCLUSIONS: The finding in this study suggests that age, decreased
      nocturnal BP and high BP variability may be additional risk factors for
      progression of glaucomatous field loss.

PMID- 8881407
TI  - [Multifocal implants of 3 optic zones: optical performance and clinical
      functional results].
AB  - PURPOSE: Evaluation of multifocal IOL (three optical zones). METHODS: Twenty
      patients were implanted. Main outcome measures were: uncorrected and best
      corrected distance and near acuity, brigthness acuity test, contrast acuity with
      differents methods: Pelli-Robson Chart, Gradual System, and spatial visual
      integration (SVI). RESULTS: Uncorrected visual acuity was restored in 94% of
      cases. Contrast sensitivity was preserved with the Pelli-Robson chart test but a
      loss of contrast sensitivity was found with the multifocal IOL with the Gradual
      system and the SVI in comparison with monofocal IOL. CONCLUSION: Multifocal IOL
      (three optical zones) allows a good restoration of both near and far visual
      acuity but a decrease in contrast sensitivity was detected.

PMID- 8881408
TI  - -Choroidal detachment associated with rhegmatogenous retinal detachment: a risk
      factor for postoperative PVR?.
AB  - PURPOSE: To determine whether preoperative choroidal detachment associated with
      primary rhegmatogenous retinal detachment is an independent risk factor for
      postoperative PVR. MATERIAL AND METHODS: One hundred eighty nine primary
      rhegmatogenous retinal detachments in 187 consecutive patients, initially
      operated on by the same surgeon, were enrolled in a prospective study. Ten eyes
      showed preoperative choroidal detachment associated with retinal detachment.
      Owing to the small number of eyes with preoperative choroidal detachment, we
      conducted the statistical analysis using the calculation of relative risk.
      RESULTS: The correlation between preoperative choroidal detachment and
      preoperative PVR grade C-D was statistically significant (RR: 9.03; confidence
      interval: 2.91-28). Postoperative PVR occurred, or recurred, in one of the 10
      eyes with preoperative choroidal detachment (10%), and 10 of the 179 eyes with no
      choroidal detachment (5.58%). The difference between the two groups is not
      statistically significant (RR: 1.79; confidence interval: 0.25-12.64). All eyes
      which developed postoperative PVR showed one or two recognized independent risk
      factors for postoperative PVR (preoperative PVR grade C-D and/or retinal tears >
      or = 90 degrees). CONCLUSION: With the treatment modalities used in the present
      series (preoperative and postoperative steroids, and vitreoretinal microsurgery)
      preoperative choroidal detachment associated with primary rhegmatogenous retinal
      detachment no longer appears to be an independent risk factor for postoperative
      PVR.

PMID- 8881409
TI  - [Multiple pilomatricoma. Apropos of a case].
AB  - Pilomatricoma is a benign, solitary tumor. The histopathologic findings of viable
      basaloid cells in the periphery, shadow cells in the central part and foci of
      calcification are characteristic of pilomatricoma. The microscopic aspect of
      multiple pilomatricomas was not different from solitary pilomatricomas. Though,
      some consider them as a pathognomonic sign of myotonic dystrophy. Complete
      surgical excision is the best management.

PMID- 8881410
TI  - [Papilledema and POEMS syndrome. Apropos of a case].
AB  - The POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal
      protein, Skin Changes) is often unrecognized by ophthalmologists. We report the
      case of a 51-year-old female suffering from a POEMS syndrome with a bilateral
      optic disc edema.

PMID- 8881411
TI  - [Ocular sites of acute leukemias].

PMID- 8881412
TI  - [Pigmentary dispersion syndrome].

PMID- 8881413
TI  - Experimental infection of three Nigerian breeds of sheep with the Zinga strain of
      the Rift Valley Fever virus.
AB  - Experimental infection of three indigenous breeds of sheep in Nigeria, namely the
      West African Dwarf (WAD), Yankasa and Ouda resulted in fatal disease with the
      Zinga Rift Valley Fever virus. Infected sheep of the three breeds responded by
      pyrexia within 24 h of infection, that lasted 6 to 7 days, but peaked between day
      2 and 4 post-infection. Viraemia coincided with pyrexia and peaked (10(9) PFU/ml)
      3 days p.i. in Yankasa and WAD sheep, but with highest titre (10(7.5) PFU/ml) in
      Ouda sheep. Zinga Rift Valley Fever virus infection of sheep was characterised by
      hyperactivity, watery and mucoid nasal discharges, projectiles and bloody
      diarrhoea, external haemorrhage and clinical manifestations of nervous disorders.
      Viraemia was followed by low level of antibody development in all the infected
      sheep. Haemotological changes included a sharp fall in the PCV, Hb concentration
      and total RBC count during the course of the disease. These changes were most
      severe in the Yankasa, followed by WAD and Ouda breeds. There were
      thrombocytopaenia, prolongation of prothrombin and clotting times in all the
      infected sheep. There was also progressive leucopaenia associated with
      lymphopaenia. The total protein and albumin levels were depressed, but the
      globulin level rose from day 5 p.i. The changes in the serum biochemical
      constituents included sharp and progressive increase in the level of alanine
      aminotransferase and aspartate aminotransferase. The sodium level decreased
      gradually while that of potassium was initially stable but later increased until
      the infected animals died. There was a significant increase in the level of blood
      urea nitrogen from day 3 p.i. that continued until the infected animals died.
      Gross and microscopic examinations of the carcasses of the infected sheep showed
      significant lesions in many organs, including disseminated intravascular
      coagulation.

PMID- 8881414
TI  - [Evaluation of vaccinal protection against rinderpest in Cameroon. III. General
      evaluation].
AB  - The national veterinary Laboratory, Garoua (Cameroon) has been carrying out
      rinderpest sero-surveillance since 1989 as part of an effort made by the
      Panafrican Rinderpest Campaign (PARC) to control rinderpest in Africa. In 1993,
      8517 serum samples collected from 286 cattle herds (from 0 to 3 years old)
      randomly chosen from six provinces with large cattle population (Far-North,
      North, Adamaoua, East, West, North-West) were tested using the rinderpest
      competitive ELISA technique; the herd immunity level was 54%. Out of 2010 serum
      samples from 68 non-protected cattle herds tested using the peste des petits
      ruminants (PPR) ELISA technique, 91 samples were positive (4.5%): this does not
      significantly increase the cattle immunity level against rinderpest. Significant
      differences in the immunity rates between provinces were observed. Suggestions to
      increase the immunity level are discussed.

PMID- 8881415
TI  - Nationwide serological survey of equine influenza in Nigeria.
AB  - The objective of this work was to examine the incidence of equine influenza
      viruses in the equine population of an area of tropical Africa where equine
      influenza virus activity has recently been reported for the first time. A
      serological survey of sera from horses and donkeys from regions of Nigeria taken
      from 1990 to 1993 was carried out and the results obtained were com-pared with
      equine sera from Western Europe (Ireland). The sera were assayed for presence of
      antibodies by both haemagglutination inhibition (HI) and ELISA using a monoclonal
      antibody to the prototype H3 equine influenza virus, A/equine/Miami/1/63. The
      results showed that equine influenza was present in horses and donkeys in all
      regions of Nigeria.

PMID- 8881416
TI  - Seroprevalences of brucellosis, Q-fever and toxoplasmosis in slaughter livestock
      in Trinidad.
AB  - Serum samples obtained from livestock (cattle, chickens, pigs, sheep, goats and
      water buffaloes) slaughtered at various slaughter houses in Trinidad were
      screened for agglutinins to three zoonosis causing pathogens. Of a total of 751
      sera tested, 2 (0.3%) originating from chickens were positive for Brucella
      abortus agglutinins using the Rose Bengal test (RBT), but both were negative by
      the tube serum agglutination test (SAT). Thirty-six (4.8%) of 749 sera were
      positive for Coxiella burnetii agglutinins by the capillary agglutination test
      (CAT) with the highest prevalence, 11.3%, detected in pig sera and the lowest,
      0%, found in sheep and goat sera. The difference was not statistically
      significant (P > or = 0.05; chi 2). Of the 131 sera tested, 26 (19.8%) contained
      Toxoplasma gondii agglutinins with prevalences ranging from 5.5% in pigs to 42.9%
      in goats. It was concluded that livestock in Trinidad are free of B. abortus
      infections, but C. burnetii and T. gondii infections exist and are being
      documented for the first time in the island.

PMID- 8881417
TI  - [Use of Trypanosoma antigen detection ELISA during an epidemiological follow-up
      in the Sideradougou, Burkina Faso].
AB  - Plasmas taken during a parasitological survey on bovine trypanosomosis were
      tested a posteriori with an antigen detection ELISA test. The objective was to
      evaluate the value of this test for epidemiological monitoring. The results were
      compared to those obtained using the usual parasitological technique (buffy coat
      examination). Of the 297 zebu cattle heads studied, 216 came from four villages
      in the pastoral zone of Sideradougou. A large eradication programme had led to
      the disappearance of tsetse in the area. Blood samples were taken during the
      rainy saison (September 1986), at the beginning (January 1987) and at the end
      (May 1987) of the dry season. The parasitological diagnosis was carried out in
      the field and plasmas were stored at -20 degrees C. The serological test was
      performed in August 1993. The incidence rates of bovine trypanosomosis obtained
      with antigen detection ELISA were low in the center of the zone. These rates
      decreased proportionally to the distance between the blood sampling area and the
      limit of the infested area. The results of the parasitological diagnosis were
      similar except for a village located on the border of the treated zone. The use
      of antigen detection ELISA confirmed the low incidence of trypanosomosis in the
      center of the area of Sideradougou following the eradication campaign. It also
      enables to obtain finer parasitological results pointing out the trypanosome
      persistence in peripheric zones, more exposed to reinfestations.

PMID- 8881418
TI  - [Prevalence of Rhinoestrus usbekistanicus (Gan 1947) in donkeys (Equus asinus) in
      Senegal].
AB  - A survey performed in Dakar (Senegal) showed, for the first time, the presence of
      Rhinoestrus usbekistanicus in donkeys in the South of the Sahara desert. Out of
      the 138 heads examined between November and June, 84% were infected by a mean
      burden of 15.9 larvae (9.7 L1, 1.8 L2 and 4.1 L3). There is a hypobiotic period
      starting in March during the dry season.

PMID- 8881419
TI  - Theileria parva (Kasoba): isolation and challenge of cattle recovered from
      infection with other Theileria parva stocks.
AB  - A pathogenic Theileria stock was isolated from control cattle during an East
      Coast Fever (ECF) field immunization trial at Kasoba near Karonga town in
      northern Malawi. A stabilate of this stock caused severe fevers and prolonged
      parasitosis in Theileria parva naive cattle, resulting in the death of 5 out of
      12 cattle despite treatment. In contrast, this parasite stock caused mild to
      moderate reactions in 17 cattle immunized with the trivalent T. parva stabilate
      except in 3 animals which developed severe reactions, and one of them died.
      Another time, cattle immunized with buffalo-derived Theileria parva (Serengeti
      transformed) resisted a potentially fatal challenge, with only mild to moderate
      reactions being recorded. The parasite stock was morphologically and
      serologically indistinguishable from Theileria parva (Muguga); it was virulent
      and could cause mortality, particularly in T. parva naive cattle. The parasite
      stock was designated Theileria parva (Kasoba).

PMID- 8881420
TI  - The prevalence of trypanosomosis in small ruminants and pigs in a sleeping
      sickness endemic area of Buikwe County, Mukono district, Uganda.
AB  - A survey of trypanosomosis in goats, sheep and pigs was carried out in Buikwe
      County, Mukono District of South Eastern Uganda between April and August 1994.
      Infection rates of 8.8% in 204 goats, 26.7% in 60 sheep and 32.4% in 68 pigs of
      all ages and both sexes were recorded. Trypanosoma brucei parasites were found in
      goats and pigs, T. congolense in sheep and pigs and T. vivax in goats and sheep.
      Infection rates were similar in both sexes of animal species and it was observed
      that T. vivax caused high levels of parasitaemia while T. brucei infections were
      associated with very low levels of parasitaemia. Trypanosoma brucei infections
      accounted for 66.7% and 30% of all infections in goats and pigs, respectively. It
      is postulated that some of these T. brucei parasites could be T. b. rhodesiense,
      the causing agent of sleeping sickness in this area.

PMID- 8881421
TI  - Development and differentiation of Schwann cells.
AB  - Using the rat sciatic nerve as a model for the study of Schwann cell
      differentiation we have identified a Schwann cell precursor, a distinct cell type
      present in developing nerves at a time when they are projecting to their target
      tissues. These cells develop into Schwann cells over a relatively short time in
      vivo. In vitro, they can generate Schwann cells if they are cultured in neuron
      conditioned medium or in the presence of neu-differentiation factors (NDF)
      (neuregulins, heregulins, glial growth factor), a recently discovered family of
      growth factors expressed at high levels in neurons. Thus neu-differentiation
      factors may be important neuro-glia signalling molecules in the Schwann cell
      lineage. Later stages in the development of Schann cells, such as differentiation
      towards a myelin phenotype, can be studied using cultured Schwann cells. These
      cells dedifferentiate both in vivo and in vitro when they are deprived of axonal
      contact. Elevation of intracellular cyclic AMP levels in the absence of cell
      division causes high levels of expression of Po, the major myelin glycoprotein.
      TGF beta s and FGFs suppress this induction, while IGFs promote it.

PMID- 8881422
TI  - Molecular pathogenesis of peripheral neuropathy.
AB  - Peripheral neuropathies can result from a failure to form or maintain the myelin
      internode or from autoimmune-mediated demyelination. Several gene defects
      responsible for the most common inherited human peripheral neuropathies referred
      to as Charcot-Marie-Tooth disease have been reported. These studies identified
      PMP-22 and connexin-32 as proteins that are essentiel for normal myelination.
      Point mutations in Po protein, PMP-22, and connexin-32 have been identified as
      causes of inherited peripheral neuropathies. In addition, studies indicated for
      the first time that alterations in PMP-22 gene dosage (trisomy and monosomy) can
      induce inherited peripheral neuropathies. Little is known, however, about how
      these gene defects cause myelin pathology. This report describes the
      distributions of proteins within the peripheral myelin internode and discusses
      how these molecules contribute to the pathogenesis of inherited and autoimmune
      peripheral neuropathy. A better understanding of the molecular composition of the
      myelin internode is essential for diagnosis and treatment of human peripheral
      neuropathies.

PMID- 8881423
TI  - Effector mechanisms in demyelinating neuropathies.
AB  - While the cause of the immune-mediated neuropathies (Guillain-Barr-e syndrome,
      GBS; CIDP; multi-focal motor neuropathy and paraproteinemic neuropathies) remains
      elusive considerable progress has been made in delineating the effector
      mechanisms that underlie myelin destruction. In GBS circulating antibodies to
      glycolipids possibly precipitated by an antecedent Campylobacter jejuni infection
      can be detected with high frequency. These antibodies may interfere with
      neuromuscular transmission and eventuate myelin damage by activating the
      complement system, providing for the generation of chemotactically active split
      products C3a and C5a, the opsonin C3b, and assembly of the membrane attack
      complex. Such antibodies may also, via binding to the Fc receptor, target
      macrophages to the myelin sheath. Corroborative evidence for a crucial pathogenic
      role of antibody-mediated complement activation is also available for the MAG
      associated neuropathies. Macrophages as decisive effector cells of myelin damage
      may also act by releasing injurious molecules such as oxygen radicals, nitric
      oxide metabolites, proteases, eicosanoids and cytokines. Demyelinative as well as
      degenerative actions have been described for the cytokines TNF-alpha and
      lymphotoxin. Increased understanding of the effector mechanisms underlying
      demyelination may aid in developing more efficacious treatments for this group of
      neuropathies.

PMID- 8881424
TI  - Experimental allergic neuritis (EAN) as a model for the immune-mediated
      demyelinating neuropathies.
AB  - The inflammatory demyelinating neuropathies (GBS and CIDP) are autoimmune
      disorders; their pathogenesis and the precise immunological target(s) remain
      unknown. Valuable insights into the immune mechanisms have been gained from the
      animal models: Lewis rat EAN and chronic EAN of rabbits. Lewis rats immunized
      with myelin or myelin proteins P2 and P0 in Freund's adjuvant develop transient
      paralysis. The pathological findings of nerve edema, perivenular lymphocyte
      infiltrates and macrophage-mediated demyelination are identical to those of GBS.
      Severity of clinical EAN and of the pathology correlate with the antigen dose
      used for immunization. In Lewis rat EAN there is firm evidence of a cell-mediated
      process. The strongest support for T-cell autoimmunity has come from the adoptive
      transfer of EAN to syngeneic animals with antigen-specific (P2 and P0)
      autoreactive T-cells. Humoral factors play a role in the demyelination. Both
      mechanisms may function synergistically, in that activated neuritogenic T-cells
      breach the blood-nerve-barrier and thus provide circulating anti-myelin
      antibodies access to the target tissues. Rabbits immunized with a single large
      multiportal dose of myelin predictably develop EAN with a chronic progressive or
      relapsing course. The clinical, electrophysiological and pathological features
      are identical to human CIDP. IgM and IgG anti-Gal C antibody titres parallel the
      disease course and have demyelinating activity. T-cell responses have not yet
      been characterized in this model. Both forms of EAN lend themselves to the study
      of very specific immunotherapies.

PMID- 8881425
TI  - [Guillain-Barre syndrome: development of concepts].
AB  - The features initially described by Guillain et Barre have been updated through
      the proposal of precise criteria even if a number of questions remain. Hundred of
      works have contributed to the evolution of these concepts. This paper is a
      summary of several opinions: 1. From nerve inflammation (lesions have been
      progressively analysed) to dysimmunity (with a combination of humoral and
      cellular dysimmunity), 2. The most frequent initial factors seems Campylobacter
      Jejuni with particular clinical correlations, 3. The acute axonal form assessed
      by some, contested by others, 4. Several varieties among which the Miller Fisher
      syndrome associated with anti-GQ1b antibodies almost constantly, 5. The treatment
      presently plasma exchanges and immunoglobulines infusion. In spite of the great
      number of papers devoted to Guillain-Barre syndrome a number of questions remain,
      and none among the varieties recently described, is unanimously acknowledged.
      However the plasma exchanges and mainly the intravenous immunoglobulines have a
      positive effect in the severe forms.

PMID- 8881426
TI  - Guillain-Barre syndrome: clinical neurophysiologic studies.
AB  - Guillain-Barre syndrome is a well-defined clinical entity corresponding to
      primary inflammatory demyelinating lesions of peripheral nerves and spinal roots
      in the majority of cases seen in Western Europe and North America. Documentation
      of conduction abnormalities characteristic of demyelination in the context of
      rapidly developing weakness confirms the clinical diagnosis of acute inflammatory
      demyelinating polyradiculoneuropathy. These abnormalities include (1) conduction
      block, (2) markedly prolonged distal latencies, (3) marked slowing of motor
      conduction velocities, and (4) absent or impersistent F responses. Other
      abnormalities are of ambiguous significance: (1) low amplitude compound muscle
      responses, (2) absent sensory nerve potentials, (3) reduction in the maximum EMG
      recruitment pattern, which may all (1, 2, and 3) indicate conduction block or
      axonal degeneration, and (4) fibrillation potentials due to breakdown of motor
      axons, a frequent non-specific effect of primary inflammatory demyelination. A
      Guillain-Barre variant due to immune-mediated primary axonal degeneration has
      also been recently described.

PMID- 8881427
TI  - [Guillain-Barre syndrome: morphological lesions and their relations with clinical
      manifestations].
AB  - Acute demyelinization of the peripheral nervous system is a characteristic
      feature of Guillain-Barre syndrome. Lesions of the spinal roots predominate with
      more or less diffuse multifocal peripheral demyelinization. Inflammatory lesions
      of the distal peripheral nervous system are less common. Segmentary
      demyelinization of nerve fibers accompanying inflammatory lesions show
      characteristic penetration of macrophages within a normal appearing myelin
      sheath. The myelin on the segments concerned is rapidly destroyed by phagocytosis
      and removed with the macrophages. Once the debris has been removed, the axons are
      remyelinized after proliferation of the Schwann cells. In monophasic cases, the
      entire processes occurs over a 2-3 week period allowing remyelinization and rapid
      functional recovery. In prolonged cases, flare-ups of demyelinization, non
      remyelinization or damage to the axons can retard recovery. The mechanism and
      impact of axon damage which accompanies demyelinization at various degrees and
      which may predominate in certain cases, is discussed here.

PMID- 8881428
TI  - [Regulation of autoreactivity by the idiotypic network and therapeutic modulation
      of autoimmunity by polyvalent intravenous immunoglobulins (IgIV)].
AB  - A beneficial effect after intravenous administration of immunoglobulins (IgIV)
      has been reported in a large number of autoimmune diseases, whether mediated by
      autoantibodies or T cells. The short-term immunoregulator effect of IgIV,
      mediated by interaction of the Fc fragment of the immunoglobulins with the Fc
      receptors on the surface of leukocytes has been thoroughly described. The
      arguments presented in this review indicate that one of the consequences of IgIV
      administration is to restore regulation of autoreactivity via a network of
      interactions between "natural" autoreactive IgG in the infusion and elements of
      the immune system. Via this network, IgIB can i) produce transient or long-term
      suppression of specific autoreactive clones and stimulation of reactive B cells
      with IgIV fragments F(ab); ii) restore normal fluctuations in natural
      autoantibody titre in the serum; and iii) modulate synthesis of cytokine
      secretion.

PMID- 8881429
TI  - The Guillain-Barre syndrome; pathogenesis and treatment.
AB  - The Guillain-Barre syndrome (GBS) is an acute immune mediated polyneuropathy.
      Diagnosis of clinically defined GBS is based upon symmetrical weakness developing
      within 4, but usually within 2 weeks and disappearance of myotatic reflexes.
      There is a large variability in clinical expression, including bulbar variants.
      Also laboratory characteristics may vary. Therefore, at present, diagnosis is
      based on the clinical parameters. In the individual patient characteristics of
      EMG, immunological and microbiological studies and sometimes pathological and
      epidemiological information may further define a more specific pattern. At
      present it seems not worthwhile to split up GBS in subgroups, although in the
      future subpatterns responding to specific therapy may be defined. The
      pathogenetic studies point at present to molecular mimicry as a possible
      mechanism in triggering off the disease. In the cranial nerve variant with
      ophthalmoplegia and ataxia antibodies against the ganglioside GQ1b are found that
      recognize similar epitopes on specific Campylobacter jejuni strains; for the
      classical ascending form similar observations are made between anti-GM1
      antibodies and C. jejuni. Treatment is in the first place supportive. Plasma
      exchange has been the first proven effective specific treatment. High dose
      immunoglobulins (IgIV) are at least as effective and in fact was somewhat, but
      significantly superior with respect to some outcome criteria in the first large
      scale clinical trial. Several studies using different treatment schedules are at
      present underway. In the Netherlands a pilot study with the combination of IgIV
      and high dose methylprednisolone gave very promising results compared to IgIV
      alone. This was in contrast with an international study evaluating
      methylprednisolone, either alone or in combination with plasma exchange. The
      combination of IgIV with methylprednisolone is now further investigated in a
      formal randomized, double blind trial aimed to include 225 patients.

PMID- 8881430
TI  - [Treatment of Guillain-Barre syndrome by plasma exchange: proposal of a
      therapeutic strategy].
AB  - Although the favorable effect of plasma exchange (PE) has been demonstrated in
      Guillain-Barre syndrome, the optimal number of PE and management at different
      degrees of gravity remain to be ascertained. A new controlled multicentric trial
      is therefore being conducted since 1986. Mid-term results show that 2 PE give
      better results than 0 in patients who are still able to walk. Inversely, 6 PE do
      not give better results when ventilatory assistance was initially required. It is
      therefore logical to propose 2PE as early as possible. Two supplementary PE can
      be used in case of disease progression. Use of high dose immunoglobulins is not
      justified except when PE is contraindicated.

PMID- 8881431
TI  - [Chronic idiopathic polyradiculoneuritis. Clinical, electrophysiological and
      histopathological aspects].
AB  - Idiopathic chronic inflammatory polyradiculoneuropathies are probably due to
      dysimmune mechanisms. They form a distinct entity defined by clinical,
      electrophysiological, histopathological criteria and by their evolution and
      response to treatment. The homogeneity of that syndrome, the exact nature of the
      underlying pathological processus, the natural history and the responses to
      treatment are still debated. Need to more studies, especially of immunologic
      nature, to precise limits and criteria of such a syndrome. Chronic
      polyradiculoneuropathy is different from acute form mainly by evolution. Within
      the chronic form, the progressive and relapsing forms can be distinguished with
      different electrophysiologic characteristics. These 2 forms share the same
      electrophysiologic aspect of chronic demyelination which is characterized by
      slowing of nerve conduction, conduction block and temporal dispersion. They had
      some specific different features such as the heterogeneity of the conduction
      failure and the multifocal distribution of demyelinating lesions. The
      histopathologic lesions are those of demyelination-remyelination with some degree
      of axonal damage, although inflammatory infiltrates are not frequent. In the
      majority of cases, the motor deficit is dominant although pure sensory forms have
      been reported. In few cases, central nervous system involvement is described.
      Idiopathic polyradiculoneuropathies had different electrophysiologic features
      than polyneuropathies associated with IgM monoclonal gammopathy and anti-MAG
      activity, these later presenting more distal and homogeneous abnormalities.

PMID- 8881432
TI  - [Multifocal motor neuropathies with persistent conduction blocks: a form of
      inflammatory demyelinating neuropathy].
AB  - Since the first cases described in 1986, multifocal motor neuropathy with
      persistent conduction blocks (MMN) appears to be a well-defined nosological
      entity. Clinical features include male-predominant occurrence, weakness often
      accompanied by cramps and fasciculations; topography of the motor involvement is
      characterized by assymetry, upper limb predominance, relation to the distribution
      of individual nerves or roots. Atrophy is variable but can lack despite severe
      weakness. Multifocal, purely motor and persistent conduction blocks are the
      electrophysiological hallmark of the disease. Serum antibodies against
      ganglioside GM1 are frequently associated with MMN but their diagnostic
      sensitibity and specificity are discussed. However high level of these antibodies
      may be a useful immunological marker of MMN. Their pathogenic role is probable,
      perhaps by their interaction with ionic channels localized in node of Ranvier.
      Morphological findings, immunologic abnormalities and improvement with
      intravenous immunoglobulin therapy define MMN as a type of inflammatory
      demyelinating neuropathy. Their relation with CIDP are discussed.

PMID- 8881433
TI  - [Anti-GM1 gangliosides antibodies in multifocal motor neuropathies].
AB  - In a study on 67 chronic neuropathies, we have shown that anti-GM1 antibodies are
      particularly frequent in multifocal motor neuropathies (MMN) with conduction
      blocks (17/24 cases). The detection of these antibodies by ELISA necessitates a
      confirmation by immunodetection on thin-layer chromatography, so as to
      distinguish the anti-GM1 antibodies present in MMN from natural antibodies which
      are polyreactive and of low affinity. There is no direct correlation between the
      anti-GM1 antibody titer, the immunosuppressive treatment and the clinical
      evolution. Nevertheless, the detection of high titer of anti-GM1 antibodies is an
      additional argument in favor of treatment by IVIg.

PMID- 8881434
TI  - [Treatment of multifocal motor neuropathies].
AB  - Multifocal motor neuropathy is characterized by a progressive asymetrical
      weakness, predominantly affecting the upper limbs with persistent conduction
      blocks on motor but not sensory nerves. Treatment woth prednisone and plasma
      exchanges have failed to demonstrate any positive effects. Some improvements have
      been reported with cyclophosphamide. Mainly immunoglobulin therapy has been
      evaluated with a beneficial response in almost 70% of the cases. These benefits
      obtained over periods of less than six months have recently been confirmed by a
      long-term evaluation of 18 patients treated by repeated infusions.

PMID- 8881435
TI  - Treatment of patients with chronic inflammatory demyelinating polyneuropathy.
AB  - Patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) have
      progressive weakness of at least 2 months. In randomized trials, efficacy has
      been shown for prednisone, plasma exchange (PE) and intravenous immunoglobulin
      (IVIg). A recent trial showed equal efficacy for PE and IVIg. Since IVIg has no
      serious side effects and is relatively easy to administer, it may be the first
      treatment choice. IVIg treatment is shown to be effective in the majority, but
      not in all patients with CIDP. The proportion of patients that improves after
      IVIg seems to be roughly up to 70-90%. Patients with signs and symptoms of an
      active disease and clear involvement of both arms and legs appear to have the
      highest chance to improve after IVIg treatment, but additional or prospective
      studies are needed to verify these criteria. Most patients with initial
      improvement need intermittent IVIg treatment to maintain their improved clinical
      condition. Prognostic factors are analyzed now that may predict not only the
      initial chance to respond after IVIg treatment, but also the necessity for long
      term intermittent treatment to prevent relapse. New studies should not only
      compare the efficacy and safety of IVIg with other treatments during the initial
      treatment period, but should also look for the cost-benefit ratio during long
      term treatment regimens.

PMID- 8881436
TI  - Overview: the concept of motor neuropathy.

PMID- 8881437
TI  - [Physiopathology of monoclonal IgM associated with peripheral neuropathy].
AB  - Monoclonal IgM associated with a peripheral neuropathy often feature an antibody
      activity directed against the myelin-associated-glycoprotein. The main
      characteristics of the structure of these IgM are reviewed: the variable gene
      repertoire used by these antibodies is rather large. The VH genes belong to the
      different variability subgroups; this also holds true for the VL repertoire
      although the single V kappa 4 gene may be used quite often. These variable
      segments often exhibit somatic mutations clustered in the CDR regions suggesting
      an antigen driven process. The monoclonal IgM is produced by a B cell clone which
      may be undetectable in the majority of patients. Nevertheless, it is possible to
      detect clonal B cells in the blood which have the remarkable capacity to
      differentiate spontaneously in vitro to plasma cells. This process is dependent
      upon an IL6-autocrine differentiation pathway which may be modulated by some
      drugs such as interferons or all trans retinoic acid.

PMID- 8881438
TI  - [Peripheral neuropathies associated with IgM monoclonal gammopathy: clinical and
      electrophysiological aspects].
AB  - Polyneuropathies associated with IgM monoclonal gammopathy (IgM-MG) are the most
      frequent type of peripheral neuropathy (PN) associated with monoclonal
      gammopathy. The pathogenic relevance of IgM-MG in PN is supported by several
      arguments, the more significants are pathological data on neuromuscular biopsies
      and the demonstration of IgM antibody activity to peripheral nerve antigens,
      mainly myelin-associated-glycoprotein (MAG) and sulfated glucuronyl paragloboside
      (SGPG). In addition recently reported series show that there is a significant
      correlation between clinical/electrophysiological data of PN, and IgM-MG antibody
      activity, in more than 75% of cases. Those features are in favour of an immune
      mediated disease.

PMID- 8881439
TI  - [Anti-glycoconjugate antibodies and dysglobulinemic or dysimmune peripheral
      neuropathies].
AB  - Different anti-glycoconjugate auto-antibodies are described to be associated with
      peripheral neuropathies; the anti-MAG monoclonal IgM activity is determined by
      ELISA or immunoblotting essays, anti-glycolipid activity by ELISA or
      chromatography and monoclonal gammopathies by commercially available kits. These
      investigations are limited by possible cross-reactions due to the common
      glycosilate epitope. The peripheral neuropathies with anti-glycoconjugate auto
      antibodies are different: Guillain-Barre syndrome and its variants (anti-GM1,
      GQ1b, LM1, GD1, GD1a gangliosides or sulfatides), motor neuropathy (anti-GM1
      ganglioside), sensory neuropathies (anti-GD3, GD1b, GD1a, GQ1b gangliosides or
      sulfatides), and chronic myelinic neuropathy with IgM gammopathy (anti-MAG). We
      review the major clinical and electrophysiological features and discuss the
      underlying pathophysiological mechanisms.

PMID- 8881440
TI  - [Peripheral neuropathies and monoclonal dysglobulinemias: contribution of
      morphological study].
AB  - The association between a peripheral neuropathy (PN) and a monoclonal
      dysglobulinemia has often been reported. A causative link is however not always
      easy to establish. Therefore, to demonstrate with certainty that the
      dysglobulinemia is actually responsible for the PN, various clinical,
      electrophysiological and immunological criteria are employed. As a result of our
      personal experience, we wish to emphasize the benefit of the histological and
      immunopathological findings revealed by the nerve biopsy of these patients. The
      nerve biopsy results have, in addition, been combined and compared with the
      results of an indirect immunofluorescence study of the sera of these patients on
      normal human nerve. The results of these studies have permitted us, in about 70%
      of cases, to ascertain the mechanisms in question: the role of an eventual
      chemotherapy, the dysimmune process, the presence of abnormal immunoglobulins in
      the nerve, amyloidosis deposits, infiltrations of nerve parenchyma by abnormal
      cells, a combination of one or several of these mechanisms, etc... We were able
      to divide our 70 patients into 4 groups: group 1: "direct link" (55-60% of the
      cases), group 2: "indirect link" (10-15%), group 3: "no link" (10%), and group 4:
      "undetermined link" (about 20%). Analysis of group 1 revealed a statistically
      significant association between PN and type IgM Kappa MGUS.

PMID- 8881441
TI  - [Pro-inflammatory cytokines: a pathogenic key of POEMS syndrome].
AB  - The Polyneuropathy, Organomegaly, Endocrinopathy, M protein, Skin changes
      (POMEMS) syndrome is a rare multisystem disorder of obscure pathogenesis,
      associated with osteosclerotic myeloma. Unlike multiple myeloma without
      neuropathy, circulating levels of proinflammatory cytokines (IL-1 beta, TNF-alpha
      IL-6) are increased in patients with POEMS syndrome. Sites of IL-1 beta
      production include lymph node and bone marrow tissues. These data support the
      view that pleiotropic effects of proinflammatory cytokines released secondary to
      a strong activation of the monocyte/macrophage system, take part in the
      multisystemic expression of the disease.

PMID- 8881442
TI  - [Treatment of peripheral neuropathies associated with IgM anti-myelin monoclonal
      gammopathy].
AB  - Effective therapy of peripheral neuropathies associated with a serum monoclonal
      IgM remains difficult. Chemotherapy with Chlorambucil yielded a moderate
      improvement in only a third of the patients. No additional benefit was given with
      plasma exchanges. However they can be used in case of rapid worsening or of motor
      of the disease. Intravenous immunoglobulins were not effective in a recent
      prospective controled study. However, in this study a-interferon yielded
      improvement in more than half of the patients. These results have to be confirmed
      and mechanism of action of a-interferon needs to be elucidated.

PMID- 8881443
TI  - Molecular biology techniques in endocrinology.

PMID- 8881444
TI  - Comparison of tests of stress-released cortisol secretion in pituitary disease.
AB  - OBJECTIVES: We wished to compare peak and incremental rise in plasma cortisol in
      response to insulin induced hypoglycaemia (IIH) stress test, i.m. glucagon
      stimulation test (IMGST) and short Synacthen test (SST) in patients with
      pituitary disease, using a modern radioimmunoassay for cortisol. We compared the
      three stimulants using receiver operator characteristic (ROC) plots, assuming a
      cortisol threshold of 500 nmol/l or 580 nmol/l for the IIH stress test which we
      used as the standard from which to evaluate the SST and the IMGST. PATIENTS AND
      DESIGN: We prospectively studied 16 patients (8F, 8M mean age 43.69 +/- 3.72
      years) admitted to the investigation ward for IIH stress test and who were asked
      to undergo two additional tests (IMGST and SST) on consecutive days.
      MEASUREMENTS: We measured serum cortisol at baseline, 30, 45, 60, 90 and 120
      minutes during the IIH stress test; baseline, 150 and 180 minutes during GST, and
      baseline and 30 minutes during the SST. RESULTS: There was a significant rise in
      cortisol from baseline in all tests (P < 0.001). There was no significant
      difference among the peak plasma cortisol responses or the incremental rises in
      plasma cortisol following IMGST, SST and IIH stress test (repeated measures ANOVA
      F = 0.704, P = 0.503; F = 0.238, P = 0.79). The ROC plots clearly showed that the
      SST has poor diagnostic utility at both IIH thresholds, compared with the IMGST.
      CONCLUSION: The peaks and incremental rises in cortisol following all three tests
      are comparable. Using the insulin induced hypoglycaemia stress test as a
      reference and peak cortisol thresholds of 500 and 580 nmol/l as discriminating
      variables, the short Synacthen displayed poor diagnostic utility when compared to
      the i.m. glucagon stimulation test. The short Synacthen may be misleading if used
      as a screening test as advocated by a number of authors.

PMID- 8881445
TI  - Laparoscopic trans-peritoneal adrenalectomy: a preliminary report of 14
      adrenalectomies.
AB  - OBJECTIVES: Laparoscopic adrenalectomy offers the potential benefits of a smaller
      operation with more rapid hospital discharge, compared to open surgery. Only a
      few small series have been reported so far. We describe our preliminary
      experience of 14 adrenalectomies using this new technique. DESIGN: Review of all
      adrenalectomies (with the preoperative intention of laparoscopic removal)
      performed in an endocrine unit whose surgeon already had abdominal laparoscopic
      experience, particularly with cholecystectomy. PATIENTS AND MEASUREMENTS: Twelve
      patients (3 with Conn's syndrome, 3 Cushing's syndrome, 1 Cushing's disease, 2
      phaeochromocytomas and 3 adrenal incidentalomas) were operated between September
      1993 and February 1996. Operating times, operative technique, time from surgery
      to discharge, outcome and all complications were recorded prospectively.
      Comparative data were obtained from 14 consecutive open adrenalectomies performed
      by the same surgeon between February 1989 and February 1995. RESULTS: Fourteen
      glands were removed, two with a cholecystectomy, in 12 operations. Operating time
      (mean (range) 120 (60-225) min) was reduced with experience. Positioning the
      patient in the right lateral position facilitated left adrenalectomy. Time to
      discharge (mean (range)) was 5.3 (1-12) days. There were relatively minor
      complications in three patients, including two with Cushing's syndrome: a hernia
      at a port site, intra-peritoneal/wound haemorrhage and a pressure sore. Time to
      discharge for open adrenalectomy (mean (range)) was 6.5 (2-11) days and one case
      was complicated by wound infection. CONCLUSIONS: Laparoscopic adrenalectomy is a
      practical technique for appropriately trained surgeons who regularly undertake
      adrenalectomy. The smaller incisions offer potential advantages, particularly for
      patients with poor tissue quality due to Cushing's syndrome, but tissue
      haemorrhage may still be a problem in these patients. Time to hospital discharge
      was similar to that for open surgery.

PMID- 8881446
TI  - Petrosal sinus sampling for diagnosis of Cushing's disease: evidence of false
      negative results.
AB  - OBJECTIVE: While inferior petrosal sinus (IPS) sampling correctly diagnoses
      pituitary-dependent Cushing's syndrome if a significant ratio of plasma ACTH
      between the IPS and the peripheral blood is demonstrated, little has been said
      about the significance of a negative ratio in Cushing's disease (e.g. a false
      negative result). This study evaluates the results of IPS sampling in patients
      with Cushing's disease, and compares them with both imaging findings and
      transsphenoidal examination. DESIGN: The results of IPS sampling were
      retrospectively compared with both imaging findings and transsphenoidal
      examination. IPS samples were obtained before and 2, 5 and 10 minutes after
      intravenous administration of 100 micrograms of CRH. PATIENTS: Thirty-two
      patients with Cushing's disease were evaluated. All subsequently underwent
      transphenoidal examination of the pituitary gland. MEASUREMENTS: The ratio of the
      ACTH concentrations at the IPS and in the peripheral blood (IPS:P ratio), and the
      ratio of the ACTH concentrations between the IPSs (interpetrosal ratio) were
      calculated. Radiographic evaluation of the pituitary gland was performed with
      magnetic resonance imaging (MRI, 29 cases) or computed tomography imaging (CT, 3
      cases). RESULTS: Transsphenoidal examination of the pituitary gland revealed a
      microadenoma in 27 cases. Radiological imaging showed a signal compatible with a
      microadenoma in 22 cases (68.8%), and correctly located the tumour at the side
      found at surgery in 14 of the 22 cases with positive transsphenoidal findings
      (MRI 13 cases, CT 1 case, overall 63.6%). Successful bilateral catheterization
      was accomplished in 30 patients (93.8%). Samples before and after CRH stimulation
      were drawn in 24 cases. No major complications were observed with the technique.
      IPS catheterization correctly predicted Cushing's disease (by means of a
      significant IPS: P ACTH ratio) in 27 of the 30 patients (90%) with basal
      sampling, and in 23 of the 24 cases with samples drawn before and after CRH
      administration (95.8%). Taking into account the 12 patients with a lateral
      microadenoma shown at transsphenoidal examination, IP sinus ACTH ratio was in
      agreement with the side recorded by the neurosurgeon in 8/12 cases (66.7%). MRI
      correctly located the tumour in 8/12 patients (66.7%). One patient showed no
      significant IPS: P ACTH ratio in any set of samples. His MRI showed no sign of a
      microadenoma. Two years later, another pituitary MRI evaluation showed a midline
      hypodense signal. The transsphenoidal examination revealed a microadenoma and the
      post-operative plasma cortisol and urinary free cortisol fell to 293 nmol/l and
      100 nmol/24 h, respectively. CONCLUSIONS: Only when a significant IPS:P ACTH
      ratio is present can Cushing's disease be established by IPS sampling. The
      absence of a significant IPS: P ACTH ratio does not necessarily imply ectopic
      secretion of ACTH, nor does it exclude Cushing's disease. The results of
      lateralization by IPS sampling do not remove the need for a thorough
      transsphenoidal examination of the contents of the sella turcica.

PMID- 8881447
TI  - Vasopressin levels in Cushing's disease: inferior petrosal sinus assay, response
      to corticotrophin-releasing hormone and comparison with patients without
      Cushing's disease.
AB  - BACKGROUND: Higher vasopressin (AVP) levels have been found in the inferior
      petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the
      contralateral one, suggesting a potential pathogenetic role of AVP in Cushing's
      disease. DESIGN: In order to investigate AVP release, plasma ACTH and AVP
      concentrations were assayed in the inferior petrosal sinuses and in the
      peripheral blood before and after CRH stimulation. PATIENTS: Twenty patients with
      Cushing's disease and 12 with other pituitary diseases were subjected to
      simultaneous and bilateral inferior petrosal sinus sampling for diagnostic
      purposes. Ten healthy sex and age-matched subjects served as control for
      peripheral AVP values. MEASUREMENTS: Plasma ACTH concentrations were measured by
      RIA using commercial kits. Plasma AVP concentrations were assayed by RIA in
      acetone extracts of 1-2 ml plasma. RESULTS: Plasma AVP levels in the inferior
      petrosal sinuses were significantly higher in Cushing's disease than in patients
      with other pituitary diseases (P < 0.05) and in both groups AVP levels were
      higher in the inferior petrosal sinuses than in the peripheral blood (P < 0.01).
      In Cushing's disease, ACTH, but not AVP levels, were higher in the inferior
      petrosal sinus ipsilateral to the adenoma than in the contralateral one (P <
      0.01). Seven patients showed a significant ACTH and AVP increase (greater than
      50% of baseline) after CRH stimulation in the inferior petrosal sinus ipsilateral
      to the adenoma. Conversely, no change was found in AVP levels in the remaining 13
      patients. When AVP values were analyzed in relation to surgical cure, higher
      inferior petrosal sinus levels (P < 0.05) were found in 6 patients with poor
      outcome: 4 of these patients had significantly decreased plasma AVP
      concentrations (by 32-43% of baseline) after CRH bolus. Peripheral AVP levels
      were similar in healthy subjects and patients with Cushing's disease whereas they
      were significantly reduced in patients with other pituitary diseases (P < 0.002).
      CONCLUSIONS: The results of this study show that patients with Cushing's disease
      and poor surgical outcome had the highest AVP levels in our series. CRH
      administration caused different effects on AVP levels: it increased them in 35%
      of patients whereas there was no response in the remaining patients. On the basis
      of these findings, it is hypothesized that AVP might be involved in the
      persistence of ACTH hypersecretion in a subset of patients poorly responsive to
      surgery.

PMID- 8881448
TI  - Exophthalmos in Cushing's syndrome.
AB  - OBJECTIVE: Exophthalmos was noted in 4 of the 12 patients reported by Harvey
      Cushing in 1932. Although exophthalmos has often been included in clinical
      descriptions, no previous study has reported actual measurements in patients with
      active and treated Cushing's syndrome, and in control patients. The aim of this
      study was to obtain these measurements. PATIENTS: Thirty-one patients with active
      Cushing's syndrome (19 iatrogenic), 15 with treated Cushing's syndrome, 18 with
      Graves' ophthalmopathy, 59 control patients, and 3 patients with active Cushing's
      syndrome plus a family or personal history of thyroid disease. DESIGN AND
      MEASUREMENTS: A consecutive series of patients with active and treated Cushing's
      syndrome were assessed. They were compared with patients with Graves'
      ophthalmopathy, and with control patients. Exophthalmos was assessed by the
      author using a Hertel meter. Urinary free cortisol was measured on patients with
      Cushing's syndrome, and serum thyroxine was estimated for them, and for the
      patients with Graves' ophthalmopathy. RESULTS: Exophthalmos exceeding 16 mm (> 2
      SD above normal mean) was found in 45% of active Cushing's syndrome, 21% of
      iatrogenic Cushing's syndrome, 20% of treated Cushing's syndrome, 2% of normal
      controls, and 77% of patients with Graves' ophthalmopathy. No patient with
      Cushing's syndrome had significant symptoms due to exophthalmos. CONCLUSION:
      Patients with active Cushing's syndrome have statistically significant
      exophthalmos. This rarely causes symptoms, and diminishes when cortisol
      concentrations become normal. Cushing's syndrome and autoimmune thyroid disease
      may coexist in patients with exophthalmos.

PMID- 8881449
TI  - Overnight metabolic fuel deficiency in patients treated conventionally for
      hypopituitarism.
AB  - BACKGROUND: Hormone replacement in hypopituitary adults attempts to reproduce
      normal physiology. Conventional regimens fail to mimic normal hormone profiles
      over 24 hours. OBJECTIVE: To investigate the metabolic consequences of
      conventional hormone replacement in hypopituitary adults by measuring circulating
      levels of the major fuels, glucose, non-esterified fatty acids (NEFA), glycerol
      and 3-hydroxybutyrate (3-OHB) over 24 hours in hypopituitary subjects and
      controls. SUBJECTS: Ten GH and adrenocorticotrophin deficient hypopituitary
      adults on conventional replacement and 13 controls matched for age, sex and body
      mass index were studied. The patients received replacement with hydrocortisone
      twice daily (at 0730 and 1730 h; mean (range) daily dose 22 (10-30) mg/24 h) but
      not with GH. Other hormones were replaced as clinically necessary. MEASUREMENTS:
      Circulating glucose, NEFA, glycerol and 3-OHB levels were measured over 24 hours
      together with concentrations of cortisol (total and free), GH and insulin, and
      urinary free cortisol. RESULTS: Levels of glucose, NEFA and 3-OHB were lower in
      patients than controls (mean +/- SEM) (4.3 +/- 0.1 vs 5.3 +/- 0.1 mmol/l, P =
      0.0001; 291 +/- 46 vs 448 +/- 48 mumol/l, P = 0.015; 78 +/- 8 vs 136 +/- 24
      mumol/l, P = 0.035, respectively) before breakfast. This decrease in glucose,
      NEFA and 3-OHB was observed in the patient group throughout the night, from
      midnight to breakfast. For NEFA, the decrease persisted throughout the 24 hours.
      Glycerol did not differ significantly in patients and controls. Integrated levels
      of total and free plasma cortisol, and 24-hour urine cortisol excretion, were
      normal in patients but total and free plasma cortisol concentrations overnight
      were markedly decreased (overnight area under the curve (AUC) of total cortisol:
      440 +/- 154 vs 1593 +/- 267 nmol/l h, P = 0.0024; overnight AUC of free cortisol:
      24 +/- 8 vs 161 +/- 26 nmol/l h, P = 0.0001). GH levels were low throughout the
      whole 24 hours in the patient group (24-hour AUC: 10.6 +/- 5.1 vs 74.6 +/- 19.6
      mU/l h, P = 0.008). CONCLUSIONS: Hypopituitary adults on conventional hormone
      replacement regimens have low concentrations of metabolic fuels, glucose, non
      esterified fatty acids and 3-hydroxybutyrate throughout the night, possibly
      related to GH deficiency or to decreased overnight circulating cortisol levels.
      This overnight fuel deficiency may underlie the mechanism for the non-specific
      symptoms, such as fatigue and headache in the early morning, which are frequent
      in this group of patients.

PMID- 8881450
TI  - Cytokine expression in human anterior pituitary adenomas.
AB  - OBJECTIVE: There is increasing evidence for the role of cytokines in pituitary
      differentiated function and tumorigenesis, but the spectrum of cytokines found in
      the pituitary is unknown. Therefore profiles of cytokine expression were
      determined in different human anterior pituitary adenoma sub-types. DESIGN: The
      reverse transcriptase-linked polymerase chain reaction (PCR) was used to identify
      the presence of cytokine mRNA within human pituitary adenomas. PATIENTS:
      Seventeen pituitary adenoma biopsies removed at transsphenoidal surgery were
      examined: 4 somatotrophinomas, 7 non-functional adenomas, 4 prolactinomas, one
      case of Cushing's disease and one case of Nelson's syndrome. MEASUREMENTS: RNA
      was extracted from each adenoma biopsy and reverse transcribed into cDNA. This
      was specifically amplified in a PCR using oligonucleotide primers complementary
      to each cytokine. The cytokines investigated were interleukin (IL)-I alpha, IL-I
      beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, tumour necrosis factor (TNF)-alpha, TNF
      beta and transforming growth factor (TGF)-beta 1, beta 2 and beta 3. The products
      of each PCR were visualized using agarose gel electrophoresis. RESULTS: All 17
      adenomas expressed IL-8 transcripts, but no expression of IL-2, IL-5 or IL-7 was
      found. IL-6 was expressed in all 4 somatotrophinomas, 3 of 7 non-functional
      tumours, 2 of 4 prolactinomas and in the single case of Nelson's syndrome. At
      least one of the 3 isoforms of TGF-beta was found in all but 2 tumours; one
      prolactinoma and one non-functional adenoma. IL-1 alpha, IL-beta, IL-4, TNF-alpha
      and TNF-beta were expressed sporadically by individual adenomas. CONCLUSION:
      These data suggest that whilst IL-8 may be important, the local expression of the
      cytokines IL-2, IL-5 and IL-7 is not important in human anterior pituitary
      tumorigenesis.

PMID- 8881451
TI  - Follicle stimulating hormone-beta subunit gene is expressed in parallel with a
      transcription factor Ad4BP/SF-1 in human pituitary adenomas.
AB  - OBJECTIVES: A transcription factor Ad4BP/SF-1 is implicated in the
      differentiation of gonadotrophs in the pituitary gland, but it is not known
      whether human pituitary cells express this factor. The present study aimed to
      disclose (1) whether human pituitary adenomas express Ad4BP/SF-1, and (2) if this
      is the case, what kinds of adenoma express the factor. MATERIAL: Total RNA was
      extracted from 23 pituitary adenomas obtained by transsphenoidal surgery, and
      subjected to Northern blot analyses using cDNAs of bovine Ad4BP/SF-1, porcine FSH
      beta, LH-beta and glycoprotein hormone-alpha (GPH-alpha) subunts as radiolabelled
      probes. These adenomas included 13 clinically non-functioning adenomas, 1 GH/PRL
      producing adenoma, 6 GH-producing adenomas, 2 PRL-producing adenomas and 1 ACTH
      producing adenoma. RESULTS: The expression of Ad4BP/SF-1 exactly coincided with
      the expression of FSH-beta. Thus 5 out of 13 clinically non-functioning adenomas
      expressed Ad4BP/SF-1 and only these 5 adenomas expressed FSH-beta. Interestingly,
      only one of the GH-producing adenomas also expressed Ad4BP/SF-1 as well as FSH
      beta. GPH-alpha was expressed in 4 non-functioning adenomas and 2 hormonally
      functioning adenomas, but did not necessarily coincide with Ad4BP/SF-1
      expression. None of the 23 adenomas we tested expressed LH-beta, probably because
      LH-beta-producing adenomas are rather rare. CONCLUSIONS: The expression of FSH
      beta was parallel with Ad4BP/SF-1 expression, indicating that the expression of
      Ad4BP/SF-1 is restricted to cells derived from gonadotroph lineages in human
      pituitary adenomas.

PMID- 8881452
TI  - Loss of heterozygosity studies at the retinoblastoma and breast cancer
      susceptibility (BRCA2) loci in pituitary, parathyroid, pancreatic and carcinoid
      tumours.
AB  - OBJECTIVE: Allelic deletion of the retinoblastoma (Rb) gene on chromosome 13 has
      been reported in both pituitary and parathyroid tumours. We have investigated the
      roles of the Rb and the hereditary breast cancer susceptibility gene (BRCA2),
      which lie within 25 cM of each other on chromosome 13q12-14, in the multi-step
      aetiology of endocrine tumours. PATIENTS AND MEASUREMENTS: Seventy-seven
      endocrine tumours (43 anterior pituitary, 22 parathyroid, 7 carcinoid, and 5
      pancreatic islet cell tumours) with paired leucocytes have been examined for loss
      of heterozygosity (LOH) at the Rb and BRCA2 loci by using specific
      oligonucleotide primers for the PCR amplification of microsatellite polymorphisms
      at three intragenic Rb markers, Rb1.20, Rbi4 and D13S153, and D13S260 which is
      linked to the BRCA2 locus. RESULTS: Seventy-five of the 77 tumour-leucocyte pairs
      were informative and LOH was detected in 1 of 16 non-functioning pituitary
      tumours, 1 of 8 prolactinomas, 3 of 19 parathyroid adenomas and 1 of 1
      parathyroid carcinoma. All the 3 parathyroid adenomas with LOH were associated
      with aggressive clinical and histopathological features. Allele loss was not
      detected in any of the 16 somatotrophinomas, 2 corticotrophinomas, 1
      gonadotrophinoma, 7 carcinoid tumours (6 bronchial, 1 metastatic intestinal) or 5
      pancreatic islet cell tumours that were informative. CONCLUSIONS: These results
      demonstrate that allelic deletions of the 13q12-14 region occur in some pituitary
      adenomas and 16% of parathyroid adenomas. The extensive loss, which involves both
      the Rb gene and the BRCA2 locus, suggests that tumour suppressor genes in this
      region other than Rb or BRCA2 may be involved in the development and progression
      of some endocrine tumours.

PMID- 8881453
TI  - Thyroid hypoechogenicity after methimazole withdrawal in Graves' disease: a
      useful index for predicting recurrence?
AB  - OBJECTIVE: A characteristic thyroid ultrasonographic picture with diffuse or
      scattered low echogenicity has been described in Graves' disease (GD). Thyroid
      hypoechogenicity in GD at onset has been considered a prognostic index of relapse
      after medical treatment; moreover, thyroid hypoechogenicity is regularly observed
      in GD at the onset, but not in patients with 'burned-out' disease. The aim of
      this study was to evaluate the usefulness of thyroid hypoechogenicity changes in
      predicting GD relapse. DESIGN: Longitudinal prospective study of previously
      untreated patients with GD. PATIENTS: Thirty-nine consecutive patients aged 10-72
      years were treated with methimazole (MMI) for 12-24 months on a titration
      regimen. Evaluation of patients in remission or with relapse was done 12 and 24
      months after MMI withdrawal. MEASUREMENTS: Thyroid ultrasonography and TSH
      receptor antibodies (TRAb) were evaluated in basal conditions and then one month
      after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same
      observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3
      marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were
      considered as normal. RESULTS: Twelve and 24 months after withdrawal, there were
      10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid
      hypoechogenicity score nor TRAb values evaluated in basal conditions, showed
      significant differences between patients remaining euthyroid and those who became
      again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was
      significantly lower at the withdrawal than in basal conditions (1.1 +/- 1.1 vs 2
      +/- 0.8; P < 0.0001); it was significantly lower in patients in remission (P <
      0.001), but not in those who relapsed. The thyroid hypoechogenicity score at
      withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10
      (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in
      19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who
      relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score
      at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with
      respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the
      relapse of hyperthyroidism at the 24th month. CONCLUSIONS: Basal thyroid
      hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment
      induces evident changes in thyroid hypoechogenicity, mainly in patients who
      subsequently go into remission. The absence or a low grade of thyroid
      hypoechogenicity after MMI treatment seems to be a favourable prognostic index of
      remission of hyperthyroidism in GD.

PMID- 8881454
TI  - Reversible primary hypothyroidism with blocking or stimulating type TSH binding
      inhibitor immunoglobulin following recombinant interferon-alpha therapy in
      patients with pre-existing thyroid disorders.
AB  - OBJECTIVE: Treatment with recombinant interferon-alpha (rIFN-alpha) may induce
      autoimmunity. We have evaluated the effect of rIFN-alpha on pre-existing thyroid
      disease with special reference to changes in TSH receptor antibody. DESIGN AND
      PATIENTS: Five patients, who had a history of autoimmune thyroid disease
      diagnosed between 2 and 16 years earlier (three patients had Graves' disease
      while two had Hashimoto's thyroiditis), were treated with rIFN-alpha for chronic
      hepatitis C. Before, during and after rIFN-alpha therapy, we determined thyroid
      function, antithyroid antibody, thyroid echogenicity and the surface phenotype of
      the peripheral and intrathyroidal lymphocytes. RESULTS: Four of the patients
      developed overt hypothyroidism after 4-7 months of rIFN-alpha therapy, and two of
      them had a preceding history of low-uptake thyrotoxicosis. Recovery of thyroid
      function was observed in all four patients. Strongly positive blocking type TSH
      receptor antibody was detected and an increase in the percentage of CD19 positive
      cells in the intrathyroidal lymphocytes was also observed in three of the
      patients even though the goitre size increased in two of them. One of the
      patients became thyrotoxic later when stimulating type TSH receptor antibody
      became positive. Another patient suffered from reversible hypothyroidism although
      stimulating type TSH receptor antibody remained strongly positive throughout the
      clinical course. CONCLUSIONS: Our data thus indicated a high incidence of an
      unusual type of reversible hypothyroidism with TSH receptor antibodies in
      patients with chronic hepatitis C and pre-existing autoimmune thyroid disease
      after recombinant interferon-alpha therapy through a mechanism involving both the
      humoral and cellular immune systems.

PMID- 8881455
TI  - The prevalence of affective disorder and in particular of a rapid cycling of
      bipolar disorder in patients with abnormal thyroid function tests.
AB  - OBJECTIVE: Cognitive and affective functioning is sensitive to changes in thyroid
      hormones. We have sought to determine: (1) the prevalence of thyroid function
      abnormalities in a psychiatric population on admission (as compared to the
      prevalence in a normal population), and (2) whether such thyroid function
      abnormalities are associated with the occurrence or development of cognitive and
      affective disorders. DESIGN: Serum was collected 2-3 weeks after hospitalization
      in 3 major clinics from 3756 psychiatric patients in 1987-1990, stored, and
      assayed in 1993 for the presence of antibodies against the TSH-receptor and
      thyroperoxidase (TPO-Ab) and for TSH levels. The psychiatric cohort was matched
      with a control population of healthy individuals living in the same area (n =
      1877). The prevalence study was followed by a case-control study involving
      patients from one clinic that had routinely assigned a DSM-IIIR classification to
      its patients. Cases were those admissions with thyroid abnormalities and three
      subgroups of cases were randomly formed demonstrating either TSH less than 0.4
      mU/l (n = 44) or over 4.0 mU/l (n = 44), or TPO-Ab positivity (n = 50). Cases
      were compared to random controls from the same psychiatric population, viz
      patients without thyroid abnormalities (n = 83). Comparison was with respect to
      their psychiatric follow-up diagnosis (the investigator was blinded to the
      thyroid test results). RESULTS: Prevalence study. The percentage of patients
      positive for TSH-receptor-Ab was 0.26 (9/3504), for TPO-Ab was 10.0 (331/3316)
      and outside the TSH range of 0.4-4.0 mU/l was 10.0 ((332/3316): 5.9% (198/3316) >
      4.0 mU/l and 4.1% (134/3316) < 0.4 mU/l). Abnormal total thyroxine levels were
      found in only 9.8% of subjects with abnormal TSH, indicating the predominantly
      subclinical character of the thyroid alteration. In comparison, the healthy area
      controls over 55 years of age showed the same prevalence of positive TPO
      antibodies and TSH under 0.4 mU/l, but a higher prevalence of TSH over 4.0 mU/l.
      CASE-CONTROL STUDY: In the case control analysis differences could not be noticed
      with regard to prevalences of dementia, schizophrenia or other psychiatric
      illnesses apart from the prevalence of affective disorders which were more
      prevalent in TPO-Ab positive patients and patients with a low serum TSH. Since
      prior use of lithium, carbamezapine, carbimazole and/or thyroxine could be a
      factor of importance in this association, analyses were also carried out
      excluding patients with such prior drug use. In these analyses affective
      disorders were still more prevalent in patients with a low serum TSH
      (particularly in males, 40% in cases vs 9% in controls, P < 0.05). The most
      significant association was however between TPO-antibody positivity (and in
      particular with high titre and/or with TSH > 4.0 mU/l) and a subgroup of the
      affective disorders, viz with a rapid cycling of bipolar disorder (18% in cases
      vs 0% in controls, P < 0.001). CONCLUSION: Though causal relations cannot be
      determined from this cross-sectional study, this admission survey found early
      forms of autoimmune thyroid disease, sometimes characterized only by TPO-Abs,
      highly significantly associated with rapid cycles of a bipolar disorder. It also
      found a weak association between subclinical hyperthyroidism (low serum TSH
      without TPO-Ab positivity) and affective disorder.

PMID- 8881456
TI  - 11 beta-hydroxylase deficiency: management of a difficult case by laparoscopic
      bilateral adrenalectomy.
AB  - A 14-year-old girl presented with short stature and progressive virilization. She
      had not undergone the menarche. On investigation, she had elevated testosterone,
      androstenedione, dihydroepiandrosterone sulphate and 17 alpha-hydroxyprogesterone
      levels, which were all suppressed by overnight dexamethasone to within their
      normal ranges. An initial diagnosis of 21-hydroxylase deficiency was revised to
      11 beta-hydroxylase deficiency after a tetracosactrin stimulation test, which
      showed only a modest rise in 17 alpha-hydroxyprogesterone level (from 92 nmol/l
      at baseline to 133 nmol/l at 60 minutes) and measurement of the basal 11
      deoxycortisol, which was grossly elevated. Treatment with dexamethasone 0.5 mg
      nocte resulted in suppression of androgens in the daytime, but not in the
      evening, particularly androstenedione. Treatment with hydrocortisone 10 mg b.d.
      failed to suppress testosterone or androstenedione over a 24-hour period.
      Addition of cyproterone and oestrogen supplements had no effect and significant
      virilization persisted. Laparoscopic bilateral adrenalectomy was therefore
      performed as definitive treatment and resulted in remarkable clinical and
      biochemical improvement. This case illustrates difficulties in correct diagnosis,
      choice of appropriate steroid regimen and monitoring efficacy of treatment in
      congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. More
      aggressive management with earlier bilateral adrenalectomy may be appropriate in
      selected cases.

PMID- 8881457
TI  - Homozygous nonsense mutation in the insulin receptor gene of a patient with
      severe congenital insulin resistance: leprechaunism and the role of the insulin
      like growth factor receptor.
AB  - Severe congenital insulin resistance in the syndrome of leprechaunism is caused
      by mutations in the insulin receptor gene. We report a patient with leprechaunism
      who was homozygous for a mutation resulting in the absence of cell surface
      insulin receptors. To determine whether the receptor for Insulin-like growth
      factor-I (IGF-I) is involved in the phenotype of leprechaunism, we studied the
      effect of insulin and of IGF-I on cells from this patient. The patient had a
      homozygous C-->T substitution at base pair 8212 in exon 12 of the insulin
      receptor gene, creating a premature stop codon. This nonsense mutation is in the
      extracellular portion of the receptor and truncates the insulin receptor proximal
      to its transmembrane anchor, resulting in the absence of cell surface insulin
      receptors. This finding indicates that complete absence of the insulin receptor
      is compatible with life. Secondly, DNA synthesis was studied in skin derived
      fibroblasts in response to increasing concentrations of either insulin or Insulin
      like growth factor-I (IGF-I), and was assessed by 3H-thymidine incorporation. In
      this patient's cells, both of these hormones increased 3H-thymidine
      incorporation, and the effect was blocked by alpha-IR3, a monoclonal antibody
      that blocks activation of the IGF-I receptor. These findings confirmed the
      absence of the insulin receptor and indicated that insulin acts here through
      activation of the IGF-I receptor. These data support the contention that the
      phenotypic and metabolic abnormalities of leprechaunism result from the
      combination of lack of insulin receptor action and over-activation by insulin of
      the type 1 IGF receptor.

PMID- 8881458
TI  - Homozygous mutation in the insulin receptor.

PMID- 8881459
TI  - Leuprolide suppression of androgen secretion by hilus cell hyperplasia within the
      wall of an ovarian cyst.
AB  - Androgenic manifestations coexisting with hilus cell hyperplasia adjacent to a
      tumour or an ovarian cyst are extremely rare. We report the case of a post
      menopausal woman with hirsutism associated with hilus cell hyperplasia within the
      wall of an ovarian cyst. The pattern of steroid secretion revealed increased
      testosterone release. Suppression of testosterone to 'normal range' was seen in
      response to leuprolide administration. This new approach demonstrates
      gonadotrophin dependence of hilus cell hyperplasia within an ovarian cyst.

PMID- 8881460
TI  - Aldosterone changes during angiotensin III and potassium infusions in patients
      with primary aldosteronism.

PMID- 8881461
TI  - Acromegaly and thyroid carcinoma.

PMID- 8881462
TI  - The short Synacthen and insulin stress tests in the assessment of the
      hypothalamic-pituitary-adrenal axis.

PMID- 8881463
TI  - [Intravenous withdrawal of infected cardiac pacemaker electrodes. Apropos of 5
      cases].
AB  - Infection of a cardiac pacemaker and its electrodes is one of the most serious
      complications after implantation of a pacemaker, as it can be life-threatening
      and constitutes an absolute indication for complete withdrawal of the implanted
      material which, up until recently, could only be performed by thoracotomy or
      sternotomy with or without cardiopulmonary bypass. A new transvenous technique
      for complete removal of the infected pacemaker system has been recently
      described. We report 5 cases of infected pacemaker systems in which this
      technique was used successfully allowing withdrawal of 10 electrodes and thereby
      avoiding the need for a major surgical operation.

PMID- 8881464
TI  - [Isolated left superior vena cava: value of intraoperative echocardiography for
      implantation of a cardiac pacemaker].
AB  - The authors report the case of a patient presenting with isolated left superior
      vena cava, for which intracardiac implantation of a cardiac pacemaker was
      facilitated by intraoperative transthoracic ultrasonographic detection of the
      course of the ventricular catheter. Transoesophageal ultrasonography confirmed
      the diagnosis and eliminated a possible associated malformation.

PMID- 8881465
TI  - [Rheumatoid aortic insufficiency. Apropos of a case treated by mechanical valve
      replacement. Review of the literature].
AB  - Rheumatoid valve lesions have been described for a long time in the literature.
      The authors report a case of rheumatoid aortic incompetence presenting with
      complete heat failure and treated semi-urgently by mechanical valve replacement.
      The pathological lesions observed on the aortic valves were pathognomonic of
      rheumatoid arthritis. Transthoracic echocardiography should be systematically
      proposed in the context of severe rheumatoid arthritis looking for valvular heart
      disease.

PMID- 8881466
TI  - [Spontaneous dissection of coronary arteries. Apropos of 2 new cases with
      favourable course].
AB  - The authors report two new cases of spontaneous coronary dissection and discuss
      the real frequency of this disease as well as their generally reported poor
      prognosis. One case was a 32-year-old female migraine-sufferer treated by beta
      blockers, who developed a rudimentary anterior myocardial infarction. The other
      case was a 43-year-old man who presented with a threatened anterior myocardial
      infarction without myolysis documented by cardiac enzymes. Both patients were
      smokers and both had an excellent outcome, clinically and on stress tests, with a
      follow-up on medical treatment alone of thirty months for the first case and
      fourteen months for the second case. These two new cases had a good prognosis, in
      contrast with the majority of cases published.

PMID- 8881467
TI  - [Transposition of the external jugular vein onto the subclavian vein in the
      treatment of symptomatic stenosis of the right subclavian vein].
AB  - Subclavian vein stenosis is a classical complication of longterm venous
      catheterization in hemodialysis. We report the case of a 74 years-old woman,
      operated for multiple arteriovenous fistulae, admitted to hospital with upper
      limb oedema. Venous angiography demonstrated subclavian stenosis. Surgical
      treatment was performed by transposition of the external jugular vein onto the
      subclavian vein with a good result.

PMID- 8881468
TI  - [Efficacy and tolerability of trandolapril in overweight hypertensive patients].
AB  - An open multicentre study, performed in 340 overweight (body mass index: BMI > or
      = 25), hypertensive (95 mmHg < or = DBP < 115 mmHg) patients, evaluated the
      clinical and metabolic safety of trandolapril and confirmed its antihypertensive
      activity. After a two-week washout period, the patients received trandolapril 2
      mg as a single morning dose for 12 weeks. Doubling of the dosage was authorized
      after the first four weeks when the DBP remained higher than 90 mmHg with a fall
      in DBP < 10 mmHg. Of the 287 patients who completed the study, 15.1% had to
      receive a double dose of trndolapril during the second treatment period. After
      four weeks of treatment, SBP was decreased by 18.6 mmHg, DBP was decreased by
      13.4 mmHg and 63.1% of patients were controlled. After three months of treatment,
      SBP was decreased by 23.3 mmHg, DBP was decreased by 16.8 mmHg and 84.7% of
      patients were controlled. Subgroup analysis, according to the BMI (BMI > or = or
      < 30), showed that the fall in blood pressure was identical regardless of the
      BMI; the proportion of patients treated with a double dose of trandolapril was
      also independent of the BMI. A second subgroup analysis, according to the
      waist/hips ratio, did not reveal any difference according to the android or
      gynoid profile of excess weight. Twelve patients (3.9%) dropped out of the trial
      because of adverse events, 10 of which were attributable to treatment; 6.5% of
      patients reported an adverse effect attributable to treatment. Laboratory assays
      performed before and after three months of treatment demonstrated the very good
      metabolic safety profile of trandolapril, in view of the slight but significant
      reduction of total cholesterol, triglycerides and blood glucose. However, an
      average weight loss of one kilogram was reported. The global safety was
      considered to be good or excellent by the investigators in 94.8% of cases.

PMID- 8881470
TI  - Anastomosis between both hypoglossal nerves in a 30 mm human embryo.
AB  - In this paper we present the first description of an anastomosis between both
      hypoglossal nerves during the embryonic period, a very uncommon anatomical
      variation. This was observed in a 30 mm crown-rump (C-R) length human embryo
      (Carnegie stage 23) from the Bellaterra Collection (Prof. Domenech Mateu),
      stained for nerve fibers. The anastomosis consisted of a large diameter trunk
      (36.7 microns) situated in front of and slightly below the hyoid cartilage, and
      clearly distinguishable from the anastomosis found in adults, which has a very
      fine diameter and is located in the suprahyoid region.

PMID- 8881469
TI  - Morphological aspects of the vascularization in intraventricular neural
      transplants from embryo to embryo.
AB  - Intraventricular transplants of neural tissues were performed in ovo from embryo
      to embryo. Fragments of the nervous wall of the optic lobe (tectum) from 14-day
      chick or 12-day quail embryos (donor) were inserted into the ventricle of the
      right optic lobe of 6-day chick or 5-day quail embryos (host). Chick-to-chick,
      chick-to-quail and quail-to-chick grafts were carried out. The vascularization
      changes occurring in the host tectum and in the grafted neural tissues were
      analysed under light, transmission, and scanning electron microscopes and by
      morphometric methods. In the host embryo tectum, the neural graft stimulates a
      statistically significant increment in vessel density and a vessel sprouting into
      the ventricle of the optic lobe. The vascular sprouts reach the transplanted
      tissue and establish connections with its native microvasculature. The chick-to
      quail and quail-to-chick grafts, submitted to immunoreaction with a quail
      specific antibody which recognizes an antigen (MB1) present on endothelial cells,
      indicate that re-establishment of the circulation in the graft depends upon
      anastomoses between host and donor vasculatures and the rapid new growth of host
      derived and donor-native vessels. The presence of macrophage-like cells escorting
      the new-growing vessels suggests that these cells are involved in the host and
      donor tissue angiogenesis.

PMID- 8881471
TI  - Distribution of serotonin-immunoreactivity in the brain of the pigeon (Columba
      livia).
AB  - The distribution of serotonin (5-HT)-containing perikarya, fibers and terminals
      in the brain of the pigeon (Columba livia) was investigated, using
      immunohistochemical and immunofluorescence methods combined with retrograde
      axonal transport. Twenty-one different groups of 5-HT immunoreactive (IR) cells
      were identified, 2 of which were localized at the hypothalamic level
      (periventricular organ, infundibular recess) and 19 at the tegmental
      mesencephalic and rhombencephalic levels. Ten of the cell groups were situated
      within the region of the midline from the isthmic to the posterior
      rhombencephalic level and constituted the raphe system (nucleus annularis,
      decussatio brachium conjunctivum, area ventralis, external border of the nucleus
      interpeduncularis, zona peri-nervus oculomotorius, zona perifasciculus
      longitudinalis medialis, zona inter-flm, nucleus linearis caudalis, nucleus raphe
      superior pars ventralis, nucleus raphe inferior). The 9 other cell populations
      belonged to the lateral group and extended from the posterior mesencephalic
      tegmentum to the caudal rhombencephalon [formatio reticularis mesencephali,
      nucleus ventrolateralis tegmenti, ectopic area (Ec) of the nucleus isthmo-opticus
      (NIO), nucleus subceruleus, nucleus ceruleus, nucleus reticularis pontis
      caudalis, nucleus vestibularis medialis, nucleus reticularis parvocellularis and
      nucleus reticularis magnocellularis]. Combining the retrograde axonal transport
      of rhodamine beta-isothiocyanate (RITC) after intraocular injection and
      immunohistofluorescence (fluoresceine isothiocyanate: FITC/5-HT) showed the
      centrifugal neurons (NIO, Ec) to be immunonegative. Serotonin-IR fibers and
      terminals were found to be very broadly distributed within the brain and were
      particularly prominent in several structures of the telencephalon (archistriatum
      pars dorsalis, nucleus taeniae, area parahippocampalis, septum), diencephalon
      (nuclei preopticus medianus, magnocellularis, nucleus geniculatus lateralis pars
      ventralis, nucleus triangularis, nucleus pretectalis), mesencephalon
      rhombencephalon (superficial layers of the optic tectum, nucleus ectomamillaris,
      nucleus isthmo-opticus and in most of the cranial nerve nuclei). Comparing the
      present results with those of previous studies in birds suggests some major
      serotonin-containing pathways in the avian brain and clarifies the possible
      origin of the serotonin innervation of some parts of the brain. Moreover,
      comparing our results in birds with those obtained in other vertebrate species
      shows that the organization of the serotoninergic system in many regions of the
      avian brain is much like that found in reptiles and mammals.

PMID- 8881472
TI  - Quantitative electromicroscope study of the oculomotor parasympathetic neurons
      projecting to the ciliary ganglion in cats: comparison of the synaptic (axon
      somatic and axo-proximal dendritic) organization of anterior-dorsal and ventral
      cell groups.
AB  - The synaptic organization of the oculomotor parasympathetic preganglionic neurons
      (OPNs), labeled retrogradely after a horseradish peroxidase (HRP) injection into
      the ciliary ganglion, was studied in cats by electron microscopy. We divided the
      OPNs into two groups, anterior-dorsal (ADG) and ventral (VG) cell groups, based
      upon physiological studies in cats suggesting that accomodation-related OPNs are
      predominantly located anterior and dorsal to the somatic nuclei of the oculomotor
      nuclear complex (i.e., the anteromedian and Edinger-Westphal nuclei, and the
      ventral central gray area), while pupillo-constriction-related OPNs are
      predominantly located ventral to the somatic nuclei (i.e., the ventral tegmental
      area). The synaptic organization of these two groups was quantitatively compared,
      using a nested analysis of variance to determine statistical significance (P <
      0.05). Partial reconstructions of the labeled somata and proximal dendrites were
      made from tracings of electron micrographs of every 2nd section in serial
      ultrathin sections that included the nucleolus or were adjacent to sections that
      included the nucleolus. The mean number of boutons of apposition on a
      reconstructed labeled soma of VG was significantly greater than that of ADG (mean
      +/- SD; ADG, 5.3 +/- 3.3; VG, 8.6 +/- 3.2). The mean synaptic density on a VG
      soma was significantly greater than on an ADG soma (mean +/- SD; ADG, 3.74 +/-
      2.11 counts/100 microns2; VG, 6.30 +/- 1.99 counts/100 microns2). The mean
      synaptic covering ratio on a VG soma was significantly greater than on an ADG
      soma (mean +/- SD; ADG, 5.21 +/- 2.91%; VG, 10.14 +/- 3.76%). The mean estimated
      number of boutons of apposition on a VG soma was significantly greater than on an
      ADG soma (mean +/- SD: ADG, 53 +/- 36; VG, 100 +/- 48). Boutons were classified
      on the basis of the shape of their synaptic vesicles as S-type (containing
      spherical clear synaptic vesicles) or P-type (containing both flattened and
      spherical clear synaptic vesicles). The significantly greater than on an ADG soma
      (mean +/- SD; ADG, 0.31 +/- 0.20; VG, 0.67 +/- 0.18). The differences
      demonstrated in this study reinforce, morphologically, the assumption of
      functional localization of OPNs, and further allow us to estimate the relative
      characteristics of the synaptic organization of accommodation-related OPNs and
      pupillo-constriction-related OPNs.

PMID- 8881473
TI  - Nitrergic and VIPergic neurons in the choroid and ciliary ganglion of the duck
      Anis carina.
AB  - Immunohistochemistry for neuronal nitric oxide synthase (nNOS) and vasoactive
      intestinal peptide (VIP), and NADPH diaphorase histochemistry, were applied to
      investigate neurons in the choroid and the ciliary ganglion of the muscovy duck
      Anis carina. Up to 1000 neurons in the choroid stained for NADPH diaphorase and
      showed virtually complete colocalization for nNOS immunoreactivity. Almost all of
      them co-stained for VIP, while about 90% of VIP immunoreactive cell bodies showed
      colocalization for nNOS. Two-thirds of the neurons were located, mostly singly,
      at nodes of a wide-meshed nerve plexus in the suprachoroid and were only rarely
      grouped in ganglia of up to 3 neurons. Numerous varicose nNOS/NADPH-diaphorase
      positive nerve fibers were seen around large arterial blood vessels. These fibers
      derived mainly from paravascular cell bodies that represented about one-third of
      all choroidal neurons and also displayed costaining for nitrergic markers and
      VIP. Colocalization of nNOS/NADPH-d and VIP could be demonstrated in most of the
      perivascular fibers, while slightly more VIP-positive axons in the suprachoroid
      plexus did not costain for nNOS/NADPH-d. Small-caliber blood vessels and those
      localized in the choriocapillaris were not endowed with VIP/nNOS/NADPH-diaphorase
      positive fibers. A few reactive neuronal cell bodies were also found in ciliary
      nerves, while most ciliary axons were unstained. In the ciliary ganglion a small
      subpopulation of neurons showed VIP/nNOS/NADPH-diaphorase colocalization. There
      were also nNOS/NADPH-d-positive cap-like terminals on ciliary ganglion cells. The
      presence of VIP/nNOS/NADPH-diaphorase positive neurons and nerve fibers in both
      the choroid and ciliary ganglion, and in the choroidal perivascular plexus,
      indicates peripheral nitrergic and VIPergic control of blood flow in the choroid
      of the duck.

PMID- 8881474
TI  - Synaptic organization of afferent projections to the supramammillary nucleus of
      the rat.
AB  - We studied the fine structure of afferent terminals from the preoptic area, the
      nucleus of the diagonal band of Broca, the infralimbic cortex and the
      laterodorsal tegmental nucleus within the supramammillary nucleus (SUM) using the
      anterograde tracing method of horseradish peroxidase conjugated with wheat germ
      agglutinin (WGA-HRP). Injection of WGA-HRP into the preoptic area permitted
      ultrastructural recognition of many anterogradely labeled terminals in the SUM.
      Almost all labeled terminals (99%) contained clear round synaptic vesicles and
      formed asymmetric synaptic contacts (Gray's type I). About 86% of labeled
      terminals from the nucleus of the diagonal band were asymmetric (Gray's type I),
      whereas 14% contained pleomorphic synaptic vesicles and formed symmetric synaptic
      contacts (Gray's type II). Almost all labeled terminals from the infralimbic
      cortex were located in the ventral part of the SUM, and 95% of labeled terminals
      were Gray's type I. The majority of labeled terminals (90%) from the laterodorsal
      tegmental nucleus were Gray's type I, and the remaining (10%) were Gray's type
      II. The percentage of labeled terminals with dense-cored vesicles was very high
      in terminals from the preoptic area (70%), and low in terminals from the
      infralimbic cortex (19%). Labeled terminals in all cases contacted mainly
      intermediate-sized dendrites (0.5-1.0 micron diameter). All cases had only a few
      labeled axosomatic terminals. The cases of injections into the preoptic area and
      the diagonal band nucleus had some reciprocal connections at the ultrastructural
      level.

PMID- 8881475
TI  - Oxyntic cell differentiation during physiological cell renewal in abomasal mucosa
      of adult cattle.
AB  - The origin and differentiation of the oxyntic cell lineage during physiological
      cell renewal was investigated by light and electron microscopy in the abomasal
      mucosa of adult cattle. The morphologically heterogeneous oxyntic cell population
      exhibits various developmental subtypes depending on the position within the
      oxyntic unit. Pre-oxyntic cells of the isthmus and neck represent the immature
      precursors. Though heterogeneous with respect to the degree of canalicular and
      tubulovesicular membrane development, they all contain secretory granules
      resembling those of either isthmus cells, immature surface mucous cells, neck
      cells or young chief cells. A secretory granule-free stem cell is not present in
      the bovine. Downward to the gland base genesis of canalicular as well as
      tubulovesicular membranes is gradually completed; thus pre-oxyntic cells give
      rise to mature oxyntic cells. Older degenerative oxyntic cells, primarily located
      within the gland bottom, are characterized by progressive involution of
      canalicular and tubulovesicular membranes. Towards the pit, differentiation of
      pre-oxyntic cells is associated with atypical and incomplete development of
      canaliculi and tubulovesicles. In consequence, these superficial oxyntic cells
      have a reduced secretory capacity from a morphological point of view.

PMID- 8881476
TI  - Neuronal organization of the optic tectum in the hagfish, Eptatretus burgeri: a
      Golgi study.
AB  - The neuronal organization of the optic tectum (OT) was studied in the hagfish
      using the rapid Golgi method. The OT shows laminar structure. Beginning from the
      ventricular surface, the following four concentric strata are discernible: the
      stratum ependymale, stratum periventriculare, stratum cellulare et fibrosum, and
      stratum marginale. The stratum ependymale consists of several rows of ependymal
      cells and neuroblasts lining the mesencephalic ventricle. The stratum
      periventriculare contains medium-sized and small neurons whose dendrites extend
      mainly superficially. The stratum cellulare et fibrosum occupies a wide area and
      consists of densely packed neurons and fibers. Fibers in this stratum are derived
      mainly from the bulbar lemniscus and run ventrodorsally in several bundles, among
      which numerous neurons are embedded. Neurons in the stratum cellulare et fibrosum
      are divided into large, medium-sized and small neurons whose dendrites are
      arranged in a network rather than being oriented in any particular direction.
      Some of these dendrites extend contralaterally through the commissure of the OT.
      The neurons in the stratum marginale are divided into medium-sized and small
      neurons whose dendrites extend mainly tangentially. The axons of neurons in the
      stratum periventriculare and those of a few neurons in the stratum cellulare et
      fibrosum extend rostromedially and can be traced into the stratum
      periventriculare. On the other hand, the axons of neurons in the stratum
      marginale and stratum cellulare et fibrosum run rostrally, turn ventrally and
      join fiber bundles running dorsoventrally.

PMID- 8881479
TI  - [Use of human albumin solutions in surgical anesthesia and critical care in
      adults].

PMID- 8881478
TI  - Pericapillary and distant axon terminals in the nuclei of the cat amygdala: a
      morphometric study.
AB  - According to some ultrastructural studies, the pericapillary axon terminals in
      the central nervous system (CNS) are functionally connected with the capillary
      vessel wall. Thus, it may be expected that the population of pericapillary axon
      terminals will be morphologically distinct from the terminals at a further
      distance from the capillary walls. To test this hypothesis, morphometrical
      analysis of 3,048 axon terminals was performed, comparing terminals situated in
      the close vicinity of the capillary vessel with those at a distance from the
      vessels in the lateral, basal, medial, central and cortical nuclei of the
      amygdaloid body of eight cats. The cross-sectional area and circumference of each
      identified axon terminal profile were measured, and the shape of synaptic
      vesicles and the presence of synaptic contacts and granular vesicles were
      recorded. The statistical evaluation of results was performed by means of the
      Newman-Keuls' test, Wilcoxon's test, Fisher's contingency-table test and the test
      for two coefficients of structure. The morphometric examination revealed two
      ultrastructurally distinct groups of axon terminals, pericapillary and distant
      terminals, in all the nuclei of the amygdaloid body. The differentiating features
      were the shape of the synaptic vesicles, the number of synaptic contacts, and the
      size of the axon terminals. These results further support the hypothesis of a
      functional connection between axon terminals and the capillary vessel wall in the
      CNS.

PMID- 8881477
TI  - Development of the hypothalamic vasopressin system and nephrons in Meriones shawi
      during ontogenesis.
AB  - This study has evaluated the development of the hypothalamic vasopressin system
      and nephrons of the kidney in desert rodents, Meriones shawi, which effectively
      retain water by excretion of highly concentrated urine. The vasopressin system
      was studied immunocytochemically at the 18th fetal day, at the 2nd, 13th, 27th
      postnatal days and in adulthood. The kidneys were investigated at the 2nd, 13th
      postnatal days and in adulthood using microdissection technique. Occasional
      vasopressin-immunoreactive neurons were observed as early as the 18th fetal day,
      only in the paraventricular nucleus. From the 2nd postnatal day onwards,
      vasopressin neurons increased progressively in number, being mainly concentrated
      in the supraoptic and paraventricular nuclei, as well as in the ventral
      retrochiasmatic region. Transient neuronal populations were also observed at the
      13th postnatal day in the lateral preoptic area and anterior hypothalamic
      nucleus. Apart from the neurons, the glandular cells of the tuberal lobe showed
      immunostaining from the 18th fetal day, the first age studied, until the 13th
      postnatal day. The fibers of differentiating vasopressin neurons grew towards the
      circumventricular/neurohemal organs, terminating in the organum vasculosum of the
      lamina terminalis and the lateral ventricles as early as the 18th fetal day, as
      well as the third ventricle, the posterior lobe and the external zone of the
      median eminence between the 2nd and 13th postnatal days. The kidney in 2-day-old
      Meriones comprised nephrons at different stages of development from an S-shaped
      body to well-differentiated nephrons. At the 13th postnatal day, as in adulthood,
      the nephrons were well differentiated and characterized by long, thin loops
      descending to different levels of papilla. Thus, according to our morphological
      data the hypothalamic vasopressin neurons and nephrons in the kidney of Meriones
      reach the definitive state by the end of the 2nd postnatal week.

PMID- 8881480
TI  - [A study of practice patterns of albumin administration in surgical patients by
      anesthetists].
AB  - The establishment of guidelines has to take into account the current practice
      patterns. For the preparation of the consensus conference organized by the French
      Society of Anesthesia and intensive care (SFAR) on the prescription of albumin,
      an interview with a questionnaire was undertaken in order to assess the practice
      patterns of anaesthetists during the perioperative period. A group of 498
      anaesthetists were interviewed during a congress. Two out of three prescribe
      albumin. In case of haemorrhage, the decision to administer albumin depends on
      the limits for using other colloids (for 65% of the responders), the amount of
      blood loss (46%) and albuminaemia (for only 26%). In other cases, albumin is
      mainly administered in the burn patient and for recurring ascite; albuminaemia is
      a decision criterion for one anesthetist out of two. About 25% of them use a 20%
      concentration, another 25% of them a 4% concentration and the remaining 50% use
      both concentrations. Adverse effects have been seen in less than 5% of the
      responders. These data have been presented at the consensus conference and can
      also be used for the assessment of the impact of the guidelines after their
      publication.

PMID- 8881481
TI  - [Mechanisms of water exchanges: the Starling equation].
AB  - This review considers the main mathematical models used in the understanding of
      transvascular fluid exchanges and oedema formation. Models by Starling, Kedem
      Katchalsky and Wiederhielm are briefly described. The main factors which
      determine the value of the physical parameters involved in these models are the
      osmotic and interstitial pressures in plasma and tissue. With regard to the
      regulation of interstitial osmotic pressure, the importance of the presence of
      mucopolysaccharidic gel in the interstitial compartment creating an exclusion
      volume for proteins diffusing from plasma is underlined, as well as the
      importance of lymphatic flow, a parameter neglected in several models of
      transcapillary exchanges. Consequences of variations in venous hydrostatic
      pressure, plasma oncotic pressure, endothelial permeability are discussed using
      the described models. In case of changes combining an increase in venous pressure
      and permeability and a decrease in plasma oncotic pressure, the importance of
      correcting venous pressure relatively to protein supply is discussed.

PMID- 8881482
TI  - [Transvascular fluid exchange disturbed by capillary injuries].
AB  - Fluid exchange disorders due to capillary lesions are numerous and their extent
      depends on the underlying disease as well as the capillary structure of the
      affected organ. The inflammatory cascade, triggered by sepsis or reperfusion
      injury, is mediated by several humoral mediators and activated blood cells. These
      include pro-inflammatory cytokines, arachidonic acid, proteases, oxygen free
      radicals, polymorphonuclears, procoagulant, complement and fibrinolytic system.
      The interaction between these mediators leads to a loss of endothelial integrity,
      a loss of basment membrane and a disruption of the interstitial matrix, with
      wasting of the endothelial cytoskeleton. The alteration in permeability induces
      transcapillary exudation of water and protein in the interstitial space, leading
      to organ dysfunction, mainly the lungs and splanchnic organs. Nitric oxyde, by
      modulating the response of the endothelium to the cellular interaction may
      protect against capillary injury. Capillary "stress lesions" following
      microvascular hypertension are the physiological basis of neurogenic or high
      altitude pulmonary oedema, and overinflation injury from mechanical ventilation.
      The anatomic specific features of the cerebral capillaries resulted in the well
      known concept of blood brain barrier with it's changeing morphology. Under the
      effect of humoral mediators and cellular interactions, the endothelial cells are
      able, via a calcium-mediated mechanism, to contract and to modify capillary
      permeability, leading to vasogenic oedema.

PMID- 8881483
TI  - [Threshold values of colloid-osmotic pressure, serum albumin or protein during
      perioperative period].
AB  - The water flux across the capillary membrane is directly related to a gradient of
      hydrostatic and colloid osmotic forces. The membrane is not an absolute barrier
      to proteins. Any change in the capillary permeability tends to decrease the
      plasmatic colloid osmotic pressure. The interstitial space includes a
      perimicrovascular space and a compliant connective tissue space, where oedema
      accumulates. The lymphatics may easily drain excess filtration, but cannot clear
      constituted oedema. Primarily, the risk of pulmonary oedema determines the lower
      limit of the colloid osmotic pressure. During the perioperative period, any
      extrapolation of the colloid, osmotic pressure from protidaemia or albuminaemia
      would be approximate. Two major conclusions can be drawn from the results of
      Guyton and Lindsey. First, in the absence of left ventricular failure, a 50%
      decrease in colloid osmotic pressure does not increase extravascular lung water.
      Second, in the case of left ventricular failure, when the left atrial pressure
      exceeds 10 mmHg, a 50% decrease in colloid osmotic pressure significantly
      increases the risk of pulmonary oedema. In these experiments, an impairment in
      capillary membrane permeability is likely. As a result, the threshold at which
      extravascular water starts to accumulate cannot be precisely defined. However, in
      the perioperative period, capillary membrane permeability is frequently altered
      by the acute phase reaction. Finally, in most perioperative clinical situations,
      a 50% decrease in colloid osmotic pressure may not require any treatment.

PMID- 8881484
TI  - [Clinical practice interpretation of oncotic pressure, serum albumin and protein
      determination and their ability for guiding therapeutics in cases of disturbances
      of capillary exchanges].
AB  - The osmotic pressure of the serum proteins, the colloid osmotic pressure (COP) or
      oncotic pressure, is one of the four Starling forces determining fluid movements
      across a capillary. Theoretical and empirical formulas considering plasma protein
      or albumin concentration have been used. However, such calculations are only
      approximations, being inadequate especially when protein fractionation pattern is
      abnormal or when artificial colloids are used. It is preferable to measure COP
      directly. In healthy standing adults COP is around 25 mmHg. It is influenced by
      age, position, blood pressure and pH. The interpretation of the COP must take
      into account, on the one hand the possible variations of the other factors
      involved in the Starling's equilibrium and, on the other hand the structural and
      functional differences between systemic and pulmonary circulations. When
      capillary permeability is not altered, a decreased COP is associated with an
      increased filtration rate across the capillaries, resulting in oedema in skeletal
      muscle, skin, subcutaneous tissue, intestine and heart. The lung is relatively
      insensitive to extravascular fluid shifts caused by lowering of the COP, due to
      the efficacy of the pulmonary lymph drainage and the high pulmonary interstitial
      protein concentration. The main determinant of fluid exchange in the lung is then
      the hydrostatic force, reflected by the pulmonary artery wedge pressure. When
      capillary permeability is altered, the decreased reflectance coefficient results
      in a smaller effect of the COP on interstitial oedema formation. Several studies
      demonstrated that oedema formation in the injured tissues seems unaffected by
      changes in COP. During fluid resuscitation, COP measurement is useful for
      assessing the risks of peripheral oedema formation and additional measurements of
      pulmonary artery wedge pressure for assessing the risks of pulmonary oedema.
      Therefore COP measurement can serve as a useful guide for selection of colloids
      or crystalloids in critically ill patients, avoiding expensive albumin
      administrations.

PMID- 8881485
TI  - [Metabolism of albumin].
AB  - Albumin is quantitatively the most important plasma protein. Albumin is a major
      factor for the maintenance of intravascular oncotic pressure; it also plays a
      significant role in the transport of exogenous or endogenous substances. Serum
      albumin is synthesized at a high rate in the liver. This synthetic process is
      modified by many interrelated factors. Oncotic pressure, malnutrition, toxins and
      trauma may reduce albumin production or secretion. Hormones regulate synthesis
      and degradation. Albumin is widely distributed, however the concentration in the
      extravascular space is low, compared to that in the plasma or lymph. While
      considerable data are available concerning albumin synthesis, little is known
      about degradation and further studies are required.

PMID- 8881486
TI  - [Indications and role of albumin for vascular loading during prehospital care].
AB  - The use of albumin in prehospital care is very limited. Generally, in France,
      volume loading in acute hypovolaemia is obtained mainly with artificial colloids.
      However, albumin may be useful in the prehospital care of hypovolaemic pregnant
      women; but this indication remains theoretical. In many emergency medical
      services, albumin is available if needed, but the very rare indications and the
      technical requirements limit its use.

PMID- 8881487
TI  - [Indications and role of albumin for vascular loading in trauma patients and
      during preoperative period].
AB  - The use of albumin solutions for volume replacement remains controversial. The
      last American guidelines recommend the use of albumin for resuscitation in case
      of a contra-indication of artificial colloids or the requirement of sodium
      restriction. Recent trials did not show any beneficial effect of albumin on the
      mortality and morbidity rates. Only an improvement of the rheologic conditions
      has been found with albumin (and dextran 40), in comparison with starch and
      gelatin. On the basis of cost-effectiveness considerations, artificial colloids
      should be at this time favoured over albumin for intravascular expansion, except
      in pregnant women. For resuscitation, albumin could be used when the recommended
      upper limit of hydroxyethyl starch vol-ume has been reached and fresh frozen
      plasma not yet required. During preoperative haemodilution, low molecular weight
      hydroxyethyl starch has at least the same efficacy as albumin. When a rheological
      effect is required, albumin could be used.

PMID- 8881488
TI  - [Indications and role of albumin for vascular loading in the operating room].
AB  - Prospective clinical studies on albumin and non human colloids, administered
      peroperatively, were analysed. Only those with a level of evidence I or II were
      considered. On the basis of the cost-effectiveness ratio, albumin should not be
      the first choice treatment for peroperative plasma volume expansion. Low
      molecular weight hydroxyethylstarch is as efficient for restoration and
      maintenance of volaemia and colloid osmotic pressure. Albumin is administered
      when other colloids are contra-indicated or when their upper limit of volume has
      been reached.

PMID- 8881489
TI  - [Indications of albumin for vascular loading during pregnancy].
AB  - Albumin infusion is used during pregnancy for volume loading in preeclampsia
      and/or intra-uterine growth retardation, before regional anaesthesia for
      Caesarean section, compensation of blood loss during haemorrhages of parturition,
      as well as prevention and treatment of ovarian hyperstimulation syndrome after in
      vitro fertilization. In preeclampsia, albumin is used for volume loading before
      initiating antihypertensive therapy. However it neither decreases blood pressure,
      nor increases uterine blood flow. Before regional anaesthesia for Caesarean
      section, an infusion of albumin 5% at a rate of 15 mL.kg-1 prevents hypotension
      in mothers (P < 0.05 versus Ringer lactate) and provides better Apgar scores in
      neonates (P < 0.05). Albumin is used to treat hypovolaemia in severe ovarian
      hyperstimulation syndrome. Recent studies have shown that in patients at high
      risk of ovarian hyperstimulation syndrome, 500 mL albumin 5% administered after
      ovocytes retrieval diminished the incidence of this syndrome (P < 0.05 versus
      normal saline).

PMID- 8881490
TI  - [Indications and role of albumin for vascular loading during postoperative
      intensive care].
AB  - Prospective clinical trials comparing human albumin to other plasma volume
      expanders during the three first postoperative days in adult patients were
      analysed. Fifteen studies were selected. Nine of them concerned the evaluation
      during the immediate postoperative period, after cardiac surgery with
      cardiopulmonary bypass (CPB). Only one trial referred to hyperoncotic albumin and
      therefore did not allow to produce recommendations. However, a priori
      hyperoncotic albumin should not be used for plasma volume expansion. All other
      studies compared isooncotic albumin to crystalloid or hydroxyethylstarches (HES).
      It is concluded that albumin can be recommended neither after vascular (aortic
      abdominal surgery), nor abdominal surgery and can be replaced by Ringer lactate
      solution in a volume 1.5 to 2 times higher than with albumin. After cardiac
      surgery, mainly uncomplicated coronary artery bypass graft or valve replacement,
      albumin can be substituted by HES. These conclusions are only valid for blood
      losses below 50% of blood volume. The place of isooncotic albumin for fluid
      resuscitation in case of blood loss exceeding 50% of blood volume cannot be
      specified.

PMID- 8881491
TI  - [Is albumin administration useful in critical care for burnt patients?].
AB  - The most typical reaction of the organism after a major burn consists in
      transcapillary shift from plasma into interstitial space. Capillary
      hyperpermeability, but also changes in colloid osmotic gradient and decrease in
      interstitial hydrostatic pressure, explain the fluid shift to burned and, at
      minor importance, non burned areas during the first post-burn day. The extent of
      capillary hyperpermeability results in inefficiency of colloid infusions in
      reducing fluid shift to burned areas. Some groups advocate colloid supply from
      the eighth post-burn hour, on when hyperpermeability decreases, in non burned
      sites. However, for most groups, restoration of a functional interstitial space
      has priority during the 24 first post-burn hours, justifying crystalloid supply
      without colloids. Furthermore, colloid infusion could be responsible for delayed
      pulmonary oedema, in the first days following initial fluid replacement. After 24
      post-burn hours, in patients experiencing severe albumin depletion, infusion of
      human albumin is justified, in order to favour oedema resorption.

PMID- 8881492
TI  - [Indications and role of albumin, plasma volume expansion excluded, in the
      preoperative or postoperative management of portal hypertension].
AB  - Low serum albumin levels are common in patients with cirrhosis and liver failure.
      Decreased synthesis is the main but not the only mechanism leading to decreased
      serum levels. The consequences of low albumin concentrations are a decreased
      plasma colloid osmotic pressure and a decreased binding of liposoluble
      xenobiotics and endogenous substances. Besides the fluid accumulation in pleura
      and peritoneum, the complications directly related to low serum albumin levels
      have been only poorly assessed. An increase in serum albumin levels (by a few g.L
      1) for a few days can be achieved by the infusion of large amounts of human
      albumin (approximately 120 g over 3 days). The efficacy of this treatment has
      been only tested in association with large paracentesis: albumin infusion, which
      induces volume expansion, reduced the incidence of hyponatremia and functional
      renal failure. No significant effect on ascites production rate or survival has
      been observed. Similar results were achieved through polygelin or dextran-70
      infusions. No well-conducted controlled study on the value of albumin infusion in
      other circumstances apart from cirrhotic patients is available. In conclusion,
      albumin infusion should be reserved to the treatment of hyponatraemia or
      functional renal failure complicating cirrhosis with severe liver failure and
      marked hypoalbuminaemia, when the infusion of colloids failed to correct these
      anomalies.

PMID- 8881493
TI  - [Role of albumin in pulmonary edema and septic shock, plasma volume expansion
      excluded].
AB  - Patients with septic shock deserve a global approach. Intravascular volume
      loading is part of the treatment. However several questions remain open: what are
      the respective contributions of volume expansion and vaso-active drugs in the
      restoration of blood pressure and increase of cardiac output, which volumes and
      type of solutions should be used, which pulmonary capillary wedge pressure should
      be targetted, and which evaluation criteria are the most appropriate? Few
      experimental and clinical studies provide evidence of a superiority of colloids
      over crystalloids, although none of them has documented a reduction of mortality,
      length of stay in ICU or duration of mechanical ventilation. There are no data
      support-ing a superiority of albumin over artificial colloids, which are also
      much cheaper. Moreover, hydroxyethylstarch could have promising properties in
      case of increased capillary permeability. In summary and in agreement with the
      North American consensus conference, albumin should not be recommended for the
      treatment of septic shock, whether associated with non cardiogenic pulmonary
      oedema or not.

PMID- 8881494
TI  - [Role of substitution albumin therapy in drugs, hormones, electrolytes and
      miscellanous substances transport].
AB  - Human serum albumin (HSA) is quantitatively the most important non specific
      transport protein. HSA binds a wide variety of both endogenous and exogenous
      ligands. Hypoalbuminaemia may lead to a decreased plasma binding capability of
      some compounds. Biological/pharmacological consequences depend on the ligand and
      the target tissue. Many experimental studies suggest that hypoalbuminaemia may
      influence the metabolism and toxicity of endogenous ligands (bilirubin, metallic
      ions, oxygen radicals) and the pharmacological effect of some drugs (among
      others: furosemide, phenytoin, warfarin). The relevance of such information for
      human surgical situations remains unclear. Clinical studies are scarce and
      inconclusive. There is a lack of pertinent data supporting the necessity of HSA
      infusions in order to maintain a minimal plasma concentration and a convenient
      plasma transport. However, experimental data indicate that major hypoalbuminaemia
      should be considered with caution.

PMID- 8881495
TI  - [At what concentration should albumin be prescribed?].
AB  - Human albumin is available either as a 4 or a 20% solution. Only the latter is a
      plasma expander which increases volaemia by an amount corresponding to the four
      fold of the infused volume. In addition, the sodium load by the latter per gramme
      of albumin is five times lower as both solutions have the same sodium content.
      Therefore, when the administration of albumin is indicated, the 20% solution
      should be preferred, as well as for volume expansion as for other uses, due to a
      decreased sodium load. However, this recommendation has not been substantiated by
      comparative studies.

PMID- 8881496
TI  - [Quality control of human albumin solutions].
AB  - Human albumin is a major product of the fractionation of human plasma, with a
      long history of clinical use. While the manufacturing process of human albumin
      solutions has not undergone significant changes, these products have benefited
      from progress in pharmaceutical technology, quality control and quality
      assurance, which enhance their clinical safety. Besides the strict requirements
      of pharmacopoeia monographs which describe the minimal quality criteria with
      which products must comply, the quality of the final products relies on a careful
      in-process control, to guarantee the applicability of validated manufacturing
      processes and to prevent risks of chemical, bacteriological, viral or endotoxic
      contamination of the product. The development of new analytical methods for
      quality control and/or their increasing sensitivity also contributes to the
      improvement of the quality of these products.

PMID- 8881497
TI  - [Immediate and late complications of human albumin use].
AB  - Human albumin, considered as the most physiological solution for volume loading,
      devoid of viral risk due to the procedure of preparation, presents an excellent
      innocuousness. Some anaphylactoid reactions, ranging from erythema to cardiac
      arrest, have been reported. However, these are less frequent now, with the
      current techniques of purification. Renal, cardiac and respiratory complications
      may occur more frequently in patients presenting with severe injuries. The
      contamination of albumin by metals, especially by aluminium, is well documented.
      It requires appropriate procedures of manufacturing, and the information of the
      users about the residual concentration of aluminium. Albumin is a replacement
      solution which is safe with regard to the infectious risk, insofar as the
      production process is well controlled. However, human albumin should not escape
      the vigilance rules which guarantee, in the long term, an optimal safety.

PMID- 8881498
TI  - [Evaluation of transmission of unconventional agents by human albumin].
AB  - Transmissible spongiform encephalopathy agents (TSA) or prions induce
      neurodegenerative diseases in humans and animals. Their nature is still unknown,
      even if the main component of infectivity is identified as an abnormal isoform of
      a host-encoded protein, the prion protein (PrP). Today, no diagnostic test is
      available routinely for the detection of infected patients. TSA are resistant to
      most of the physical and chemical procedures that are efficient against other
      micro-organisms. Iatrogenic transmissions of TSA have been reported in the past:
      they always involved either brain derivatives or instruments that have been in
      contact with infected central nervous system. In an infected individual,
      infectivity is mostly detectable in brain. However, a persistent low-level
      viremia can be demonstrated in association with the white blood cells;
      infectivity is never found in plasma, serum or in red blood cells.
      Epidemiological data do not evidence any relationship between spongiform
      encephalopathies and blood transfusion. Therefore, in 1995, TSA transmission
      trough albumin is only a theoretical risk.

PMID- 8881499
TI  - [6th European meeting of the French Society of Cardiology. The cardiomyopathies.
      Paris, France, January 18, 1996. Proceedings].

PMID- 8881500
TI  - [Genetics of hypertrophic cardiomyopathies: what are the clinical perspectives?].
AB  - Considerable progress has been accomplished in the understanding of the genetics
      of familial hypertrophic cardiomyopathy over the last five years. This is a
      monogenic autosomal dominant condition with much inter- and intragenic
      variability. Four morbid genes coding for the contractile proteins have been
      identified: the heavy beta chain of cardiac myosin (14q11), cardiac troponin T
      (1q3), alpha tropomyosin (15q2), and myosin binding cardiac C protein (11p13-q
      13). In addition, other genetic localisations not yet identified are certain.
      Moreover, many mutations have been reported in the already identified genes. The
      principal clinical perspectives ot this research lie in the analysis of the
      relationships between phenotype (clinical expression) and genotype with respect
      to prognosis, the severity and morphology of the hypertrophic process, the
      reevaluation of our diagnostic criteria and the long-term follow-up of the many
      healthy carriers in the identified families. The genetic heterogeneity of the
      disease is a limiting factor in genetic counselling and there are ethical
      problems related to the absence of effective treatment.

PMID- 8881501
TI  - Genetic factors in dilated cardiomyopathy.
AB  - Recent studies have demonstrated that genetic factors are likely to play a major
      role in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). In clinical
      surveys, a familial trait has been demonstrated in 20 to 30% of idiopathic
      dilated cardiomyopathy patients (familial dilated cardiomyopathy). Molecular
      genetic studies have confirmed the clinical hypothesis of genetic heterogeneity
      in familial dilated cardiomyopathy, and are currently producing relevant advances
      in the understanding of this disease. The autosomal dominant form is considered
      to be the most frequent form of inherited idiopathic dilated cardiomyopathy.
      After the exclusion of a large series of candidate genes, the first familial
      dilated cardiomyopathy gene has been mapped to the long arm of chromosome 9. A
      second locus has been found on chromosome 1. Moreover, in two large families,
      characterized by a peculiar form of conduction delays and later development of
      myocardial dysfunction, the disease loci have been mapped to chromosome 1 and 3,
      respectively. The identification of the disease genes is in progress. In families
      with X-linked dilated cardiomyopathy, the disease gene has been identified as the
      dystrophin gene. The 5' end of the gene appears to be the critical region for the
      development of dilated cardiomyopathy without clinical evidence of muscle
      dystrophy. Furthermore, other cytoskeletal proteins, such as adhalin, could be
      involved in the pathogenesis of familial dilated cardiomyopathy. In familial
      right ventricular cardiomyopathy (or arrhythmogenic right ventricular dysplasia)
      characterized by isolated or prevalent right ventricular involvement, three
      different disease loci have been identified so far: two localized on the long arm
      of chromosome 14 and one on chromosome 1. The disease genes are still unknown and
      are currently under investigation. The study of the genetic factors at the
      molecular level is starting to elucidate the pathogenetic mechanisms of
      idiopathic dilated cardiomyopathy. These findings will also have relevant
      clinical and therapeutic implications.

PMID- 8881502
TI  - [Cardiomyopathies. Fundamental aspects].

PMID- 8881503
TI  - [Left ventricular diastolic dysfunction in cardiomyopathies].
AB  - Although physiologists have recognised for many years that cardiac performance is
      based on two functions, systolic and diastolic, it has only been in the last 15
      years that clinicians have acknowledged the essentiel role of diastole in the
      physiopathology of cardiac disease. Many studies have shown that left ventricular
      diastolic dysfunction resulting from abnormal active relaxation or changes in
      passive visco-elastic properties of the myocardium modulating its rigidity were
      responsible for decreased distensibility of the ventricle and an increase in its
      filling pressures. Therefore, the symptoms of the majority of patients with
      cardiomyopathy are due, more or less, to diastolic dysfunction. This is
      particularly the case in hypertrophic cardiomyopathy, most case of which have
      diastolic dysfunction secondary to an often asymetric distribution of the
      hypertrophy, to the disorganisation of the myocardiofibres and to interstitial
      fibrosis. With respect to advanced forms of restrictive cardiomyopathy, as their
      clinical and haemodynamic characteristics resembling constrictive pericarditis
      show, they demonstrate caricatural diastolic dysfunction. Finally, although the
      main abnormality in dilated cardiomyopathies is poor contractility, a decrease in
      ventricular compliance is constantly observed.

PMID- 8881504
TI  - [Left ventricular systolic dysfunction in cardiomyopathies].
AB  - Of the three physiopathological types of cardiomyopathy, dilated, hypertrophic
      and restrictive, it is the first which characteristically shows major left
      ventricular systolic dysfunction. The left ventricular volumes are increased, the
      ventricle becomes spherical and global ejection fraction decreases with diffuse
      or segmental wall motion abnormalities. The left ventricular mass is increased in
      an excentrical fashion with wall thinning. Isovolumic contraction is slower, the
      ejection time is shorter and, above all, the indices of contractility such as
      maximal velocity of the contractile elements ... are very abnormal and do not
      improve after positive inotropic stimulation.

PMID- 8881505
TI  - [Doppler echocardiographic investigation of cardiomyopathies].
AB  - There are three types of cardiomyopathy: hypertrophic, dilated and restrictive.
      The diagnosis and prognosis of these three types may be assessed from Doppler
      echocardiographic data. In hypertrophic cardiomyopathy, the diagnostic criterion
      is parietal hypertrophy. This hypertrophy is asymmetrical and usually affects the
      interventricular septum. Ventricular outflow obstruction is not necessarily
      present. The left ventricle is small and analysis of mitral inflow usually shows
      abnormal relaxation (E/A ratio < 1). The prognosis of this type of cardiomyopathy
      seems to be related to ventricular arrhythmias and the relationship between the
      hypertrophy and the presence of arrhythmias remains controversial. Dilated
      cardiomyopathy is characterized by ventricular walls of normal or decreased
      thickness, an increase in left ventricular dimensions and a reduction in the
      ejection fraction. An end-diastolic left ventricular dimension > 70 mm and an
      ejection fraction < 25% are poor prognostic factors. Left ventricular filling is
      abnormal and severe cases show a restrictive type of profile; in this case, an
      E/A ratio > 2 carries a poor prognostic. A mitral deceleration time of E wave <
      150 msec usually indicates a bad outcome. Restrictive types of cardiomyopathy are
      more rare, amyloidosis being the commonest cause. Symmetrical wall thickening and
      a small ventricular chamber are observed. In advanced stages with abnormal
      systolic function, an E/A mitral ratio > 2 and deceleration time < 150 msec, the
      outcome is rapidly fatal.

PMID- 8881506
TI  - Fibronectin and basement membrane in cardiovascular organogenesis and disease
      pathogenesis.

PMID- 8881507
TI  - The roles of ion channels in an inherited heart disease: molecular genetics of
      the long QT syndrome.

PMID- 8881508
TI  - A list of vertebrate cardiac ionic currents nomenclature, properties, function
      and cloned equivalents.

PMID- 8881509
TI  - Insulin-like growth factor-1 and myocyte growth: the danger of a dogma part II.
      Induced myocardial growth: pathologic hypertrophy.

PMID- 8881510
TI  - The importance of thrombus organization and stellate cell phenotype in collagen I
      gene expression in human, coronary atherosclerotic and restenotic lesions.
AB  - OBJECTIVES: Collagen synthesis is one of the major mechanisms of primary
      atherosclerotic plaque growth and is likely to be similarly important in
      restenosis. The patterns of collagen gene expression in human restenosis and
      associations with thrombosis/hemorrhage have not been described. METHODS: Using
      human coronary artery samples obtained via the atherectomy catheter, we compared
      primary plaques (40 specimens) and restenotic lesions (41 specimens) for type I
      collagen gene expression using immunocytochemistry (SPI.D8 antibody to type I
      procollagen, an intracellular precursor of mature collagen) with subsequent
      computer image analysis. RESULTS: Scattered positive cells were identified in
      specific, non-random patterns. According to logistic regression analyses, type I
      procollagen gene expression seems to be more closely associated with certain
      morphological features (organized thrombus, microvessels, regions enriched with
      stellate cells) than with belonging to a primary vs. a restenotic sample.
      However, there may be a tendency for restenotic tissue to have slightly higher
      numbers of type I procollagen-positive cells than primary lesion tissue.
      CONCLUSIONS: Symptomatic primary and restenotic lesions exhibit similar patterns
      of type I collagen gene expression. Plaque microvessels and thrombi/hemorrhages
      (common features of both kinds of advanced lesions) might stimulate collagen
      synthesis equally well irrelevant to the nature of the lesion.

PMID- 8881511
TI  - Polysensory response characteristics of dorsal root ganglion neurones that may
      serve sensory functions during myocardial ischaemia.
AB  - OBJECTIVE: To determine the response characteristics of dorsal root ganglion
      neurones that may serve sensory functions during myocardial ischaemia. METHODS:
      Extracellular recordings were made from 54 spontaneously active and 5 normally
      quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest
      dogs under control conditions and during epicardial mechanical or chemical
      stimulation and myocardial ischaemia. RESULTS: The activity of 78% of
      spontaneously active and all quiescent neurones with left ventricular sensory
      fields was modified by left ventricular ischaemia. Forty-six spontaneously active
      neurones (85%) were polysensory with respect to mechanical and chemical stimuli.
      The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active
      neurones associated with left ventricular mechanosensory endings (37 neurones)
      generated four different activity patterns in response to similar mechanical
      stimuli (high or low pressure active, high-low pressure active, high-low pressure
      inactive). A fifth group generated activity which was not related to chamber
      dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin
      modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively.
      Maximum local mechanical or chemical stimuli enhanced activity to similar
      degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique
      activity patterns in response to similar mechanical or chemical stimuli.
      CONCLUSIONS: Most myocardial ischemia-sensitive dorsal root ganglion neurones
      associated with epicardial neurites sense mechanical and multiple chemical
      stimuli, a small population sensing only mechanical or chemical stimuli. Activity
      patterns generated by these neurones depend on their primary sensory
      characteristics or those of other neurones that may converge on them, as well as
      the type and magnitude of the stimuli that impinge upon their sensory fields,
      both normally and during ischaemia.

PMID- 8881512
TI  - Effects of 17 beta-estradiol and progesterone on growth-factor-induced
      proliferation and migration in human female aortic smooth muscle cells in vitro.
AB  - OBJECTIVE: The significantly low prevalence of atherosclerotic cardiovascular
      disease in premenopausal women has been noted, and postmenopausal hormone
      replacement therapy (HRT) is associated with protection from this disease. The
      aim of this study was to investigate the effects of estrogen and progestin on
      growth-factor-induced vascular smooth muscle cell (VSMC) proliferation and
      migration in vitro. METHODS: Two cell lines of human female aortic smooth muscle
      cells (AOSMCs) were used for the study. DNA synthesis was evaluated by
      [3H]thymidine incorporation into cells. Migration assay was performed using
      modified Boyden chambers. RESULTS: The presence of estrogen receptors was
      determined by Western and Northern blot analyses. [3H]Thymidine incorporation
      into AOSMCs was induced by 10 ng/ml EGF alone, the combination of 10 ng/ml EGF
      with 2 ng/ml b-FGF-induced and 1 nM PDGF-BB alone. Migration of AOSMCs was
      induced by PDGF-BB. Since 17 beta-estradiol (E2, 10(-9) M approximately 10(-6) M)
      inhibited the [3H]thymidine incorporation into AOSMCs stimulated by above
      mitogens and the 1 nM PDGF-BB-induced AOSMC migration in a dose-dependent manner,
      estrone (E1), estriol (E3) and progesterone (P) had no significant effects. The
      combination of P (10(-9) M approximately 10(-6) M) did not show any effect on
      these inhibitory effects of 10(-7) M E2. Preincubation of AOSMCs with the anti
      estrogenic agent, tamoxifen (10(-6) M), significantly antagonized these
      inhibitory effects of 10(-7) M E2. CONCLUSIONS: These findings suggest that the
      inhibitory effect of E2 on VSMC proliferation and migration might be one of the
      factors involved in the decreased incidence of atherosclerotic cardiovascular
      disease in premenopausal women and postmenopausal HRT, and P might not affect
      these estrogenic responses.

PMID- 8881513
TI  - Modulated expression of transient outward current in cultured neonatal rat
      ventricular myocytes: comparison with development in situ.
AB  - OBJECTIVES: Developmental changes of cardiac ion channels have been characterized
      in freshly isolated mammalian heart cells. To investigate the regulatory factors
      of postnatal development in transient outward current (Ito) in cardiomyocytes,
      the modulated expression of Ito was studied in cultured neonatal rat ventricular
      cells. These changes in vitro were compared with those in situ in acutely
      isolated ventricular myocytes. METHODS: Ventricular cells were enzymatically
      isolated from day-old Wistar rats and cultured under various growth conditions
      from day 6 to 15. Whole-cell patch-clamp recording was used to study the
      functional expression of Ito. RESULTS: During development in situ from 5- to 15
      day-old stages, Ito density was doubled at day 15 with a significant increase in
      membrane capacitance (Cm) of the myocytes. Some cells were incubated in serum
      rich medium from day 6 to 15 during primary culture, revealing marked increases
      in both Cm and Ito density at day 15. However, no developmental changes in the Cm
      and Ito density were observed in serum-free medium. Under the serum-free
      condition, neither the addition of acidic fibroblast growth factor (aFGF) nor
      basic FGF (bFGF) to culture medium influenced the Cm. aFGF (10-60 ng/ml) failed
      to stimulate Ito expression. 72-h treatment with bFGF significantly promoted the
      Ito density in a concentration-dependent manner; nevertheless, prolonged
      administration from day 6 to 15 did not induce a further increase, resulting in
      lower Ito density than in age-matched freshly isolated and serum-treated
      preparations. The increase in Ito in cultured cells induced by serum and bFGF may
      be attributable to paralleling changes in the ionic selectivity of the channel,
      but was not caused by changes in the voltage-dependence of steady-state Ito
      activation and inactivation. CONCLUSIONS: bFGF and some other unknown serum
      factors may play important roles in the postnatal expression of Ito in the
      neonatal cardiomyocytes. The developmental increase in Ito and postnatal cell
      hypertrophy of neonatal cardiomyocytes can be regulated independently.

PMID- 8881514
TI  - Effect of internal sodium and cellular calcium load on voltage-dependence of the
      Indo-1 transient in guinea-pig ventricular myocytes.
AB  - OBJECTIVE: To investigate the effect of altering internal Na and cell Ca load on
      the voltage-dependence of the intracellular Ca transient. METHODS: Ventricular
      myocytes were isolated enzymatically from the guinea-pig heart. They were patch
      clamped and dialysed internally with pipette solutions which contained either 0
      or 10 or 20 mM Na. Intracellular Ca was monitored with Indo-1 and experiments
      were carried out at 36 degrees C. A standard level of Ca loading was established
      before each test pulse by applying a train of conditioning pulses. The voltage
      dependence of the Cai (Indo-1) transient provided information about the
      mechanisms which trigger Ca release from the sarcoplasmic reticulum (SR).
      RESULTS: The voltage-dependence of L-type Ca current (ICa.L) was assessed in
      separate experiments by dialysing myocytes with a Cs-based solution. ICa.L had a
      maximum amplitude at 0 mV, declined at more positive potentials and there was
      little net inward ICa.L at +100 mV. The rapid initial phasic component of the
      Indo-1 transient was abolished by ryanodine/thapsigargin; therefore, this
      component reflected the magnitude of SR Ca release. In cells dialysed with 10 mM
      Na, the voltage-dependence of the Indo-1 transient was different from ICa.L. The
      Indo-1 transient became maximal at +20 mV, and the decline of the Indo-1
      transient at positive potentials was less steep than the decline of ICa.L. A
      large proportion of the phasic Indo-1 transient could remain at positive
      potentials where there was no detectable ICa.L. Increasing dialysing Na from 10
      to 20 mM led to a marked change in voltage-dependence of the Indo-1 transient.
      With 20 mM Na, the amplitude of the phasic Indo-1 transient remained large
      between +20 and +100 mV. Removing Na from the pipette dialysis solution had the
      opposite effect on voltage-dependence of the transient. For each dialysing [Na],
      the level of cellular and SR Ca content was altered by varying the potential of
      conditioning pulses applied before each test pulse. There was no significant
      effect on voltage-dependence of the Indo-1 transient of either increasing or
      reducing the cellular Ca content. CONCLUSION: These data are consistent with the
      hypothesis that the voltage-dependence of the Cai transient results from the sum
      of the voltage-dependencies of the two main trigger mechanisms--Ica.L and reverse
      Na/Ca exchange. When a myocyte was dialysed with Na-free solution, the voltage
      dependence of the Cai transient became more similar (but not identical) to that
      for ICa.L. With 20 mM Na dialysis, the altered voltage-dependence of the Cai
      transient may reflect an increased trigger influence of reverse Na/Ca exchange.

PMID- 8881516
TI  - Localisation and differential expression of the fibroblast growth factor receptor
      (FGFR) multigene family in normal and atherosclerotic human arteries.
AB  - OBJECTIVE: Aberrant expression of FGF-1 and FGF-2 may be central to the
      atherosclerotic disease process, promoting both intimal hyperplasia and plaque
      neovascularisation. FGF-1 and FGF-2 mediate their biological effects by binding
      to a family of specific high-affinity cell surface receptors with protein
      tyrosine kinase activity. Four receptors have been identified in the human
      (FGFR1/flg gene product, FGFR2/bek gene product, FGFR3 and FGFR4), but little is
      known of their in vivo tissue distribution. Characterisation of the spatial
      distribution of the FGFR multigene family in both normal and atherosclerotic
      arteries is a prerequisite to further define the functional role of FGF-1 and FGF
      2 in atherosclerosis. The objective of this study was to examine the cell-type
      specific expression of the FGFR multigene family members in both normal and
      atherosclerotic human arteries. METHODS: FGFR expression was investigated
      immunocytochemically with polyclonal antisera to FGFR1-4 and by in situ
      hybridisation using FGFR1-4 riboprobes in archival material. Total cellular mRNA
      was analysed using poly d(T) and the levels correlated with the expression of
      FGFR1-4 mRNA. RESULTS: At the protein level, FGFR1-4 were expressed in the medial
      smooth muscle cells and adventitial vessels of normal arteries. In simple and
      advanced lesions, the expression profiles of FGFR1-4 showed variability between
      individual arteries, and cell-type-specific differential FGFR expression was
      apparent. Widespread co-expression of FGFR1 and FGFR2 was observed in intimal
      smooth muscle cells, foam cells and the plaque microvasculature of simple and
      advanced lesions. FGFR3 and FGFR4 exhibited more restricted patterns of
      distribution within the plaque. In situ hybridisation with poly d(T) confirmed
      high cellular transcriptional activity in archival atherosclerotic lesions. The
      high levels of total cellular mRNA and FGFR protein were not always reciprocated
      at the FGFR1-4 mRNA level, and only FGFR1 and FGFR2 mRNA transcripts were
      abundant in intimal lesions. CONCLUSION: These data provide evidence to suggest
      involvement of the FGF-FGFR multigene families in human atherogenesis.
      Differential FGFR expression in plaque subtypes may reflect distinct differences
      in receptor function which may be relevant to lesion progression during
      atherosclerosis.

PMID- 8881515
TI  - TNF alpha mRNA and protein in cardiac transplant biopsies: comparison with serum
      TNF alpha levels.
AB  - OBJECTIVES: To examine the role of TNF alpha (TNF alpha) in cardiac transplant
      rejection by simultaneous analysis of protein expression and its messenger RNA
      within serum and grafted tissue. METHODS: 54 endomyocardial biopsy specimens were
      taken from 19 patients at various times after transplantation. TNF alpha
      messenger RNA was localised using a digoxygenin labelled complementary DNA probe.
      An anti-TNF alpha antibody was used to immunohistochemically label the protein
      product. Serum TNF alpha levels at the time of biopsy were analysed using a
      specific enzyme-linked immunosorbent assay. RESULTS: TNF alpha mRNA was present
      in 22/34 endomyocardial biopsies. Eight also contained TNF alpha protein. None
      had protein alone. Expression did not relate to the grade of rejection in the
      present or subsequent biopsies. Serum TNF alpha was undetectable (assay
      sensitivity 30-330 pg/ml) for the majority of specimens. In the nine cases with
      elevated serum levels, eight samples were from cases within the first 30 days
      post transplant (r = -0.379; P < 0.05). CONCLUSIONS: Neither tissue TNF alpha
      mRNA, tissue protein, nor serum TNF alpha relate to the grade of rejection.
      Furthermore, TNF alpha expression within endomyocardial biopsies is not reflected
      in the serum. These findings argue against the use of serum analysis as an
      indicator of cytokine profiles within cardiac tissue allografts. The
      demonstration of a trend in the early expression of TNF alpha after
      transplantation suggests that its release may not be specific to the process of
      rejection.

PMID- 8881517
TI  - The role of fibroblast growth factor-2 in the vascular effects of interleukin-1
      beta in porcine coronary arteries in vivo.
AB  - OBJECTIVE: We recently demonstrated that chronic treatment with interleukin-1
      beta (IL-1 beta), a major inflammatory cytokine found in atherosclerotic lesions,
      induces coronary arteriosclerotic changes and vasospastic responses to serotonin
      and histamine in pigs in vivo and that those responses are partially mediated by
      platelet-derived growth factor (PDGF). This study was designed to examine, first,
      whether the effects of IL-1 beta are also partially mediated by fibroblast growth
      factor-2 (FGF-2), which is another important growth factor in atherosclerotic
      lesions, and, secondly, whether chronic treatment with FGF-2 per se also induces
      histological and functional changes in porcine coronary arteries in vivo.
      METHODS: Porcine coronary arteries were aseptically wrapped with cotton mesh
      absorbing IL-1 beta with or without neutralizing antibody to FGF-2. In a separate
      series of experiments porcine coronary arteries were chronically treated with FGF
      2 itself in the same manner. Coronary vascular responses in vivo and histological
      changes were examined 2 weeks after the operation. RESULTS: Coronary vasospastic
      responses to serotonin and histamine and neointimal formation were induced at the
      site of the coronary artery where IL-1 beta was chronically and locally applied.
      These responses were significantly suppressed by co-treatment with a neutralizing
      antibody to FGF-2 but not by that with non-immune IgG. Immunostaining revealed
      the presence of FGF-2 in the endothelial cells, the thickened intima and the
      media at the IL-1 beta-treated site. Furthermore, chronic treatment with FGF-2
      also induced coronary vasospastic responses to serotonin and histamine and
      neointimal formation. CONCLUSIONS: These results suggest that the vascular
      effects of IL-1 beta may also be mediated by FGF-2 in our swine model and that
      chronic treatment with FGF-2 also causes coronary arteriosclerotic changes and
      vasospastic responses in vivo.

PMID- 8881518
TI  - Ca-dependence of isometric force kinetics in single skinned ventricular
      cardiomyocytes from rats.
AB  - OBJECTIVES: The effects of Ca2+ on the rate of tension redevelopment following a
      brief release/restretch were investigated in single chemically-skinned
      ventricular myocytes from the rat. METHODS: The myocytes were enzymatically
      isolated and skinned using Triton-X100. They were then attached with an optical
      adhesive glue to glass micropipettes fixed to a piezoelectric translator and a
      force transducer. Tension redevelopment was measured at various levels of Ca
      activation after disrupting force-generating crossbridges by a brief (20 ms) step
      release/restretch equivalent to 20% of the original 2.1 microns sarcomere length.
      Most of tension redevelopment was well fitted by a monoexponential function.
      RESULTS: At maximal Ca concentrations, pCa 4.5 maximal force was obtained at 2.1
      microns sarcomere length and averaged 11.8 +/- 0.7 microN. The rate of tension
      redevelopment (ktr) increased with increasing Ca concentrations up to 5.19 +/-
      0.37.s-1 at maximal Ca activation. The relation between the rate of tension
      redevelopment and Ca concentration was sigmoidal and could be fitted by the Hill
      equation with coefficients similar to those describing the tension-pCa relation.
      The relation between relative rate of tension redevelopment and relative steady
      activated tension was curvilinear increasing with increasing Ca concentration.
      CONCLUSIONS: In cardiac muscle, Ca2+ modulates both the number and the kinetics
      of force-generating crossbridges in a manner similar to that previously reported
      in skeletal muscle.

PMID- 8881519
TI  - Pre-treatment with trimetazidine increases sarcolemmal mechanical resistance in
      reoxygenated myocytes.
AB  - OBJECTIVE: Cytoskeletal and sarcolemmal fragility secondary to anoxia may
      contribute to sarcolemmal rupture and cell death during reoxygenation of
      cardiomyocytes. This study investigated the influence of trimetazidine (TMZ), a
      drug with effects on lipid metabolism and cell membranes, on reoxygenation
      induced sarcolemmal rupture. METHODS: Isolated adult rat myocytes were submitted
      to 60 min of metabolic inhibition and 5 min of hypo-osmotic reoxygenation to
      simulate reperfusion edema in situ. Cells were allocated to 3 groups of
      treatment: in one group, TMZ 100 mumol/l was added to both the metabolic
      inhibition and reoxygenation buffers (group TMZ); another group was submitted to
      the same treatment but cells had previously been incubated with TMZ 100 mumol/l
      for 3 h (group TMZ-Pre); a control group underwent metabolic inhibition and hypo
      osmotic reoxygenation without any treatment. Cell morphology was monitored
      throughout the experiment and sarcolemmal integrity was assessed by
      quantification of LDH activity and trypan blue exclusion test. RESULTS: After 60
      min of metabolic inhibition most cells (83.1 +/- 2%) presented rigor contracture
      without between-group differences. Reoxygenation resulted in hypercontracture of
      84.2 +/- 2.3, 91.2 +/- 1.4 and 84.1 +/- 2.1% of cells in TMZ, TMZ-Pre and control
      groups, P = NS. The trypan blue exclusion test revealed a higher proportion of
      cells with sarcolemmal integrity in TMZ and TMZ-Pre groups than in controls (12.7
      +/- 2.0, 10.0 +/- 1.5 and 6.3 +/- 0.8%, respectively, P = 0.002). No between
      group differences in LDH activity in the extracellular medium were observed at
      the onset or at the end of metabolic inhibition. However, LDH release was
      significantly lower (P = 0.002) in the TMZ-Pre group (1.6 +/- 0.1 IU/1000 cells)
      than in the TMZ and control groups (1.9 +/- 0.2 and 2.2 +/- 0.1 IU/1000 cells).
      CONCLUSION: Preincubation of cardiomyocytes with TMZ does not prevent rigor
      contracture induced by metabolic inhibition or hypercontracture during subsequent
      reoxygenation, but does improve sarcolemmal resistance to reoxygenation-induced
      mechanical stress. This could help to explain the beneficial effect of TMZ on
      infarct size.

PMID- 8881520
TI  - Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine
      epicardium exposed to simulated ischemia.
AB  - OBJECTIVES: Myocardial ischemia results in an early phase of arrhythmias that
      primarily involves reentrant mechanisms. However, the trigger that initiates
      reentry remains unknown. We studied the initiation of reentry attending the
      development of electrical heterogeneity during simulated ischemia in isolated
      canine right ventricular subepicardium. METHODS: Preparations consisted of thin
      epicardial sheets in which action potentials were recorded at 4 sites with
      intracellular microelectrodes. Tissues were superfused with a hyperkalemic,
      hypoxic and acidotic 'ischemic' solution. RESULTS: Simulated ischemia produced a
      40-70% abbreviation of the action potential at some epicardial sites but not
      others, primarily by suppressing development of the action potential plateau (or
      dome). This typically created a marked dispersion of repolarization within the
      preparation. Local re-excitation ensued when the action potential dome propagated
      from sites where it was maintained to sites where it was abolished. This
      mechanism, termed 'phase 2 reentry', produced an extrasystole which then
      initiated one or more cycles of circus movement reentry. Tachycardias consisting
      of repetitive reentry occurred in larger tissues. The window for reentry occurred
      over a range of stimulation rates that shifted to faster rates as ischemia
      progressed. The transient outward current blocker, 4-aminopyridine, restored the
      dome at all sites by reversing the ischemia-induced abbreviation of the action
      potential. Thus, block of the transient outward current restored electrical
      homogeneity and abolished all reentrant activity within the epicardial
      preparations. CONCLUSION: Our results implicate phase 2 reentry as a new
      mechanism for genesis of extrasystoles during simulated ischemia and identify
      this mechanism as a trigger of circus movement reentry. Validation of this
      hypothesis awaits the results of future studies using high-resolution recording
      techniques.

PMID- 8881521
TI  - Endothelin-1 production in coronary circulation in a new canine model of coronary
      thrombosis.
AB  - OBJECTIVE: The purpose of this study was to investigate whether endogenous
      endothelin-1 (ET-1) production in coronary circulation is associated with acute
      coronary thrombotic events in vivo. To achieve this goal, we have designed a new
      experimental canine model of coronary thrombosis. METHODS: In vivo occlusive
      thrombus was induced by the intracoronary application of radiofrequency energy
      (660 kHz, 50 W) in closed-chest dogs. Pathological and immunohistochemical
      examinations of thrombosed coronary artery were performed. In 12 dogs,
      plasminogen activator was administered intravenously and serial measurements of
      ET-1, thromboxane B2 (TXB2) and thrombin-antithrombin III complex (TAT) levels in
      plasma from the coronary sinus, aortic root and inferior vena cava were examined.
      RESULTS: Occlusive platelet-rich thrombi were attached to the deeply injured
      intimal surface. TAT and TXB2 increased rapidly soon after the intimal injury and
      declined after successful thrombolysis. In contrast, ET-1 in the coronary sinus
      was elevated after reperfusion and was significantly higher than in the aorta.
      Net ET-1 production in the coronary circulation showed a significant positive
      correlation with the peak TAT levels (r = 0.69, P < 0.05), but not with TXB2 or
      total occlusion time as an index of ischemic severity. CONCLUSIONS: Deep intimal
      injury leads to occlusive coronary thrombus. Thrombus formation and its
      subsequent lysis is associated with the activation and deactivation,
      respectively, of the coagulation cascade and platelets. Thrombin generation may
      stimulate ET-1 production in the coronary endothelium in acute coronary
      thrombotic events.

PMID- 8881522
TI  - Tachycardia-induced failure alters contractile properties of canine ventricular
      myocytes.
AB  - OBJECTIVE: Rapid cardiac pacing has been used as a model for experimentally
      induced cardiomyopathy. However, its relevance to human heart failure is not
      clear at present because little is known about changes in size and function of
      ventricular myocytes. We have therefore studied the responses to graded increases
      in frequency and calcium in canine ventricular myocytes from failing hearts. The
      aim of our study was to evaluate the resemblance between canine pacing-induced
      and human end-stage heart failure. METHODS: Myocytes were isolated from the left
      ventricular wall of dogs that were in heart failure after 6 weeks of pacing at
      250 beats/min. Cell shortening was measured by edge detection. RESULTS: Clinical
      signs of failure included dyspnea, ascites, and heart dilatation; the hemodynamic
      parameters were: LVdP/dtmax 1613 +/- 149 vs. 4713 +/- 304 mmHg/s in 6 control
      dogs; LVEDP 17.2 +/- 4.4 vs 5.6 +/- 1.1 mmHg; LV volume 60.5 +/- 6.2 vs. 30-35
      ml. Myocytes from failing hearts were longer and thinner than those from controls
      (from factor: 0.40 +/- 0.01 vs. 0.47 +/- 0.01, P < 0.001, > 30 cells/heart). With
      6 mM Ca2+ and at 0.5 Hz, contraction amplitude was significantly attenuated in
      myocytes from failing hearts: 6.6 +/- 0.9% cell shortening vs. 10.0 +/- 0.8% in
      controls (P < 0.05). This deficit was exacerbated at higher stimulation rates.
      Time-to-peak contraction and time-to-50% relaxation were not altered. There was
      no difference in sensitivity to thapsigargin. CONCLUSION: As with cells from
      human failing hearts, contraction amplitude showed rate-dependent depression in
      this animal model, whereas features like slowing of contraction and relaxation
      and reduced sensitivity to thapsigargin, were not reproduced.

PMID- 8881524
TI  - Basic behavioral science research for mental health: thought and communication.

PMID- 8881523
TI  - Inhibition of beta- but not alpha 1-mediated adrenergic responses in isolated
      hearts and cardiomyocytes by nitric oxide and 8-bromo cyclic GMP.
AB  - OBJECTIVES: The study was carried out to assess the effect of nitric oxide (NO)
      generation or inhibition of NO synthase on the cardiac response to beta- and
      alpha 1-adrenergic agonists. In addition, we determined the effects of the cell
      permable analogue of cGMP, 8-bromo-cGMP (8Br-cGMP). METHODS: Experiments were
      done in electrically-paced isolated perfused rat hearts as well as in ventricular
      myocytes. Hearts were exposed to either the beta-adrenoceptor agonist,
      isoproterenol (0.1 microM), or the alpha 1-adrenoceptor agonist, phenylephrine (2
      microM in the presence of equimolar concentrations of propranolol), either with
      each drug alone or in the presence of the NO donors S-nitrosoacetylpenicillamine
      (SNAP, 10 microM) and 3-morpholino-sydnonimine (SIN-1, 10 microM), the NO
      synthase inhibitor L-NAME (10 microM) or 8Br-cGMP (50 microM). These
      concentrations of SNAP and 8Br-cGMP increase tissue cGMP levels approximately 3
      fold after 15 min treatment. Myocardial contractility was assessed by determining
      left ventricular pressure with a fluid-filled balloon inserted into the left
      ventricle. Similar experiments were performed in myocytes in which cell
      shortening and intracellular calcium transients were determined although
      concentrations of isoproterenol and phenylephrine in myocytes were higher (1 and
      5 microM, respectively) than those used in isolated hearts in order to achieve
      optimum responses. RESULTS: In isolated hearts isoproterenol increased developed
      pressure by about 50%, which was totally prevented by SNAP and SIN-1 and
      unaffected by L-NAME. 8Br-cGMP, however, did not significantly diminish the
      positive inotropic effect of isoproterenol. Phenylephrine increased developed
      pressure of isolated hearts by about 30%, but this was totally unaffected by
      either SNAP, SIN-1 or 8Br-cGMP. In myocytes, isoproterenol significantly
      increased the calcium transient by more than 50% and cell shortening by about
      70%. Both effects were significantly attenuated by SNAP, SIN-1 and 8Br-cGMP but
      unaffected by L-NAME. Phenylephrine significantly increased cell shortening and
      the calcium transient, but these responses were unaffected either by SNAP or 8Br
      cGMP. CONCLUSION: The present study demonstrate that NO as well as guanylate
      cyclase inhibitors and, to a lesser extent, 8Br-cGMP attenuate beta-receptor
      mediated cardiac responses and supports the concept that NO serves as an
      endogenous regulator of beta-mediated effects of catecholamines in the heart. In
      addition, our findings suggest that the antiadrenergic effects of NO are
      restricted to these receptors but likely do not involve alpha 1-mediated effects.

PMID- 8881525
TI  - Clinical psychologists as psychotherapists: history, future, and alternatives.
AB  - As managed care and other cost-containment strategies become central features of
      the American health care system, doctoral-level clinical psychologists will be
      increasingly supplanted in the role of psychotherapist by lower cost providers
      such as social workers, marriage and family counselors, and masters-level
      psychologists. To provide one basis for clinical psychologists to make judgments
      about their role in psychotherapy; this article describes what the field was like
      before psychotherapy became a core activity and then compares the present
      transition with its historical counterpart: the opening up of the psychotherapy
      profession to doctoral-level clinical psychologists after World War II. History
      suggests that efforts to resist the current changes will be unsuccessful and that
      the most adaptive coping strategy for clinical psychologists is to take advantage
      of the transition by reenvisioning training and practice of clinical
      psychologists.

PMID- 8881526
TI  - Psychology's drug problem: do we need a fix or should we just say no?
AB  - Five contextual factors give rise to the proposal that psychologists secure
      prescription privileges: (a) the historical overattachment of applied psychology
      to psychotherapy; (b) the oversupply of psychotherapists; (c) the rise of managed
      care; (d) the hegemony of syndromal classification; and (e) the weakening of the
      medical guild and rise of drug company attention to psychopharmacology. Whereas
      some of these factors present real problems for psychology, the acquisition of
      prescription privileges by psychologists is not the proper response. The cost to
      the discipline in loss of professional identify, safety, and training disruption
      is too great. Instead, the profession should build a more honorable alternative
      based on psychological science.

PMID- 8881527
TI  - The case against prescription privileges for psychologists.
AB  - The right to prescribe psychoactive medications could have major effects on the
      practice of psychology, on its education and training, on the marketing of
      psychological services, and on the public's perception of the field. This article
      presents the case against psychologists pursuing prescription privileges,
      including discussion of several arguments advanced by proponents of prescription
      privileges. Although APA has endorsed the effort to secure prescriptive
      authority, there is no requirement that states actually change their licensing
      laws so that their psychologists can prescribe. The costs (and potential risks)
      involved in pursuing prescription privileges are discussed.

PMID- 8881528
TI  - The dawn of a revolution in mental health.
AB  - Issues surrounding the debate regarding psychologists' evolution as prescribers
      are discussed in a balanced format. Arguments against prescribing are challenged,
      such as the change in focus of psychological work and the potential harm to
      public welfare. Disruption of the process of psychotherapy, through employment of
      external prescribers, is also discussed, especially given the psychological
      meaning imbued to medicine by patients. It is concluded that psychologists have
      the opportunity and responsibility to improve the present models for the delivery
      of mental health services by obtaining the requisite training and legislative
      mandate to prescribe.

PMID- 8881529
TI  - Comments on expanding the clinical role of psychologists.
AB  - The interest by psychologists in prescription privileges is welcome because it is
      a manifestation of the long overdue acknowledgement of the efficacy of medication
      for many mental disorders. The lack of national academic standards in psychology,
      however, poses a problem. Psychologists are certified in title only and are not
      licensed to perform any procedure, although there have been efforts to
      standardize the training of psychologists. Currently, states regulate the title,
      but no national educational standards exists. Therefore, psychologists are not
      able to claim they are a homogeneous patient care resource.

PMID- 8881530
TI  - Applying our medicine to the psychopharmacology debate.
AB  - Reasonable arguments can and should be made in favor of and in opposition to
      psychologists seeking prescription privileges. The debate presents psychology
      with the opportunity to converge rather than fractionate. An APA Task Force
      established in 1991 recognized that a number of preliminary issues would have to
      be addressed before the question of prescription privileges could be answered,
      and made recommendations for the types of training various psychologists would
      need. This article describes that training and discusses how psychologists in
      training may be affected by the current debate.

PMID- 8881531
TI  - Prescription privileges for psychologists.
AB  - As the profession of psychology has matured, serious interest has surfaced over
      the past decade in obtaining prescription privileges within the practitioner
      community. Other nonphysician disciplines have exercised this clinical
      responsibility for years, significantly improving their ability to
      comprehensively serve current and new populations. Efforts are underway to
      develop appropriate and viable training modules. The primary objection expressed
      by medicine is once again that our practitioners will become "public health
      hazards." Not surprisingly, resistance to change exists within psychology's
      training programs. However, the power to prescribe represents the authority to
      ensure that psychotropic medications are appropriately utilized, if used at all,
      and will ensure that psychology's practitioners can address society's pressing
      needs.

PMID- 8881532
TI  - Basic science training in psychopharmacology. How much is enough?
AB  - Training psychologists to administer psychotropic medication will require
      acquisition of a unique knowledge base and set of skills that are generally not
      components of graduate education in psychology. Nevertheless, the current level
      of basic science training in graduate education in psychology is substantial and
      should, with minor modification, allow adequate preparation for students to enter
      into specialized training to prescribe. The direct provision of
      psychopharmacology requires psychologists to demonstrate competencies in addition
      to those required in the general provision of psychological services. Such
      competencies are perhaps best taught at the postdoctoral level. The authors argue
      that all curricula training professional psychologists should be able to train
      psychologists capable of practicing as independent, full-fledged health care
      providers.

PMID- 8881533
TI  - Injury prevention...who, me?

PMID- 8881534
TI  - So, just do it...go upstream.

PMID- 8881535
TI  - Making lemonade from lemons: opportunities to integrate emergency medical care.

PMID- 8881536
TI  - Clinical wound evaluation.

PMID- 8881537
TI  - Drive-by shootings by violent street gangs in Los Angeles: a five-year review
      from 1989 to 1993.
AB  - OBJECTIVE: To determine trends in the numbers of drive-by shootings, individuals
      shot at, innocent bystanders shot at, and homicides by drive-by shootings in the
      city of Los Angeles from 1989 to 1993. METHODS: A retrospective analysis of
      police records was performed for all gang-related drive-by shootings that
      occurred in the city of Los Angeles between 1989 and 1993. RESULTS: From 1989 to
      1993, there were 6,327 drive-by shootings, 9,053 people shot at, and 590
      homicides. There was an increase in drive-by shootings, people shot at, and
      homicides between 1989 and 1991, followed by a decrease between 1991 and 1993.
      The case fatality ratio of individuals killed to individuals shot at increased
      from 1989 to 1993 (p = 0.0011). Forty-seven percent of the people shot at, and
      23% of the homicide victims, were innocent bystanders. CONCLUSION: Drive-by
      shootings are a major public health problem in Los Angeles. While the rate of
      drive-by shootings decreased in 1992 and 1993, the proportion of fatal cases
      increased. To prevent drive-by shootings, the root causes of violent street gang
      formation must be addressed.

PMID- 8881538
TI  - A prospective study of in-line skating: observational series and survey of active
      in-line skaters--injuries, protective equipment, and training.
AB  - OBJECTIVES: 1) To assess the relationship between types of injuries incurred and
      training and protective equipment worn by adults injured while in-line skating;
      2) to observe the type and amount of protective equipment worn by in-line skaters
      while skating; and 3) to survey active in-line skaters about formal training,
      protective equipment, and history of injuries incurred, and the effect of such
      injuries on the protective equipment subsequently worn. METHODS: A prospective
      study of consecutive adult patients presenting to the ED for evaluation of in
      line skating injuries; a consecutive-series observational study of active in-line
      skaters to assess protective equipment worn; and a survey of selected active in
      line skaters. Eighty-five adult patients were included who presented with a
      history of injury related to in-line skating to the EDs of an urban academic
      medical center, a suburban academic-affiliated hospital, and a community
      hospital. Four hundred eleven active in-line skaters on the Chicago lakefront
      were observed for protective equipment worn, 91 of whom participated in the
      survey. RESULTS: Of those presenting to the ED with injuries, only 15% indicated
      that they had received formal in-line skating instruction. Of the ED patients,
      50% wore no protective equipment; overall, 6% wore a helmet; 44%, wrist
      protection; 23%, knee protection; and 19%, elbow protection. Only 2% wore all of
      the above equipment. The primary mechanism of injury reported was a loss of
      balance (58%); others included collision with objects (25%), collision with
      bicycles (11%), and collision with cars (5%). Fractures or dislocations occurred
      in 48% of the patients; 6% had head injuries necessitating CT scans. Those who
      wore no protective gear were more likely to require hospital admission (p <
      0.05). Of the 411 in-line skaters observed, 157 (38%) wore no protective
      equipment. Compared with the injured group presenting to the ED, fewer observed
      participants were without protection (p < 0.05). Among those surveyed, prior
      injury was not associated with the subsequent use of protective gear. CONCLUSION:
      Patients who present to the ED for evaluation of in-line skating injuries have a
      high incidence of fractures/dislocations. Few injured or surveyed in-line skaters
      had formal training. Use of protective equipment by injured skaters was
      associated with a decreased likelihood of hospitalization. Observed in-line
      skaters more commonly wore protective gear than did those who presented to the ED
      with injuries.

PMID- 8881539
TI  - Community-wide emergency department visits by patients suspected of drug-seeking
      behavior.
AB  - OBJECTIVE: To measure community-wide ED use by patients at high risk for drug
      seeking behavior. METHODS: A retrospective, observational study was performed to
      analyze a cohort of university hospital ED patients seen January 1 to June 30,
      1990, for specific pain-related diagnoses (i.e., ureteral colic, toothache, back
      pain, abdominal pain, or headache) and either independently identified on at
      least one other local hospital's "patient alert" list or having a drug-related
      death during 1990. Patients with terminal illnesses were excluded. The frequency
      of ED (and affiliated urgent care clinic) visits and hospital admissions were
      determined for January 1 to December 31, 1990, at seven local hospitals.
      Detailed, supplemental chart review was performed for visits to three of these
      hospitals from 1990 to 1992. RESULTS: Thirty patients were identified as being at
      risk for drug-seeking behavior (mean age: 34.3 years; range: 21-55 years; 50%
      males). We identified 379 visits for this cohort (86% ED visits, 9.8% urgent care
      visits, 4.7% hospital admissions), for an average of 12.6 visits (range: 2-33)
      per patient per year. On average, each patient visited 4.1 (range: 1-7) different
      hospitals and used 2.2 (range: 1-6) different aliases. Two patients died of drug
      overdose. Supplemental chart review revealed 28 episodes (among 17 different
      patients) in which a patient was told that he or she "would receive no further
      'narcotics'" from that facility; these patients subsequently received controlled
      substances from another hospital in 93% of these instances and from the same
      facility in 71%. CONCLUSIONS: Patients identified as being at high risk for drug
      seeking behavior have high community-wide ED visit rates. Improving communication
      between and within hospitals may help identify patients who could benefit from
      more consistent community-wide care and appropriate treatment for addiction.

PMID- 8881540
TI  - The emergency department electrocardiogram and hospital complications in
      myocardial infarction patients.
AB  - OBJECTIVE: To determine whether acute myocardial infarction (AMI) patients who
      have negative ECGs on presentation have significantly lower complication rates
      than do those AMI patients who have positive ECGs on presentation. METHODS:
      Retrospective, cohort analysis comparing rates of hospital complications
      (ventricular fibrillation or tachycardia, shock, atrial arrhythmia or
      bradyarrhythmia with systolic blood pressure < or = 90 mm Hg, pulmonary edema) or
      interventions among patients with a final hospital diagnosis of AMI and an
      initially negative vs positive ECG. A negative ECG was normal or had nonspecific
      ST-segment and/or T-wave abnormalities (upright, flattened T waves; an isolated
      inverted T wave; ST depression < 0.1 mV; tall T waves with J-point elevation) or
      minor nonischemic abnormalities. Sample size was adequate to detect a 30% between
      group difference in complication rates [alpha = 0.05, 1 - beta (power) = 0.80].
      RESULTS: The 27 negative-ECG AMI patients differed from the 38 control patients
      in (mean +/- SD) age [57 +/- 12 vs 66 +/- 12 years, p < 0.01] but not in gender
      or history of AMI. The negative- and positive-ECG groups had similar rates of
      hospital complications [30% (95% CI: 13-47%) vs 42% (95% CI: 26-58%), p = 0.44]
      and intensive procedures [19% (95% CI: 4-34%) vs 29% (95% CI: 15-43%), p = 0.50],
      respectively. The negative-ECG patients with hospital complications had ECG
      evolution precede the event in 83% (95% CI: 69-97%) of cases; persistently
      negative-ECG patients had no complications [(95% CI: 0-33%), p = 0.06].
      CONCLUSIONS: Negative- and positive-ECG AMI patients do not have moderate or
      large differences in the rates of in-hospital complications. Most negative-ECG
      patients who suffer complications evolve ECG changes prior to the event and such
      changes indicate the potential need for a higher level of care.

PMID- 8881541
TI  - Variance cardiography for emergency department evaluation of chest pain patients.
AB  - OBJECTIVE: To determine the test performance of 24-lead variance cardiography
      (VC), an ECG technique that measures QRS morphologic variability, for ED
      evaluation of chest pain associated with coronary artery disease (CAD). METHODS:
      A prospective, single-blind study of VC was performed in a community teaching
      hospital ED. All chest pain patients (> 30 years of age) who, after initial
      emergency physician evaluation, were believed to have pain of potential cardiac
      etiology and were admitted to the hospital were eligible. Exclusion criteria
      included obvious noncardiac etiology for discomfort, bundle-branch block, atrial
      fibrillation, and incomplete subsequent cardiac evaluation. After initial
      evaluation and stabilization, VC was obtained. The numerical output of VC was a
      CAD index (CADI). Serum myoglobin and creatine kinase (CK)-MB levels were
      obtained at the time of presentation and after one, two, and six hours. Hospital
      records were reviewed to determine final diagnosis and in-hospital evaluation
      results. RESULTS: Fifty-two of 75 eligible patients had complete data. Final
      diagnoses were as follows: 27/52 (52%), noncardiac; 13/52 (25%), acute myocardial
      infarction (AMI); and 12/52 (23%), unstable angina due to CAD. Twenty-three
      percent (12/52) of the patients had CADIs < 75. Eleven of these were found to
      have noncardiac origins for their chest pain. The twelfth patient had a 12-lead
      ECG revealing AMI and had been given thrombolytic therapy with subsequent
      reperfusion prior to VC. Using a CADI < 75 as the cutoff for a negative study, VC
      alone had a negative predictive value of 92%, a sensitivity of 96%, a positive
      predictive value of 60%, and a specificity of 41%. CONCLUSION: A CADI < 75, in
      addition to clinical impression and initial ECG, may identify chest pain patients
      who do not have significant CAD. Further prospective assessment of VC is
      warranted.

PMID- 8881542
TI  - Sodium polystyrene sulfonate treatment for lithium toxicity: effects on serum
      potassium concentrations.
AB  - OBJECTIVE: To examine the effects of sodium polystyrene sulfonate (SPS) on serum
      potassium (K) concentrations in mice pretreated with parenteral lithium (Li).
      METHODS: A placebo-controlled murine model trial of SPS therapy following IV Li
      was performed. Sixty male CD-1 mice weighing 18-22 g were administered either IV
      LiCl (125 mg/kg) or a control solution (normal saline). Half of the mice in each
      of these groups were then given orogastric water 20, 40, 90, 150, and 210 minutes
      after LiCl or normal saline; the other half received SPS (5 g/kg/dose) at
      equivalent times. Subgroups of each of these four groups were sacrificed at one,
      two, and six hours after pretreatment and the serum was analyzed for K
      concentration. Serum K concentrations for the various groups were compared with
      analysis of variance and Newman-Keuls tests for the comparison of multiple means.
      RESULTS: A statistically significant reduction of serum K concentrations occurred
      in the animals that received SPS treatment following either IV saline or LiCl
      solutions. The degree of K reduction that resulted from the combination of LiCl
      and SPS treatment (35% reduction at six hours, compared with the placebo-treated
      controls) was larger than that which resulted from either IV Li with oral water
      (15% reduction) or IV saline with oral SPS (20% reduction). CONCLUSIONS: These
      findings suggest that development of hypokalemia may represent a potential
      limitation in the use of SPS in the treatment for Li toxicity.

PMID- 8881543
TI  - The impact of health maintenance organization care authorization policy on an
      emergency department before California's new managed care law.
AB  - OBJECTIVE: To examine the effect on patient care of HMO-mandated calls for
      authorization prior to ED evaluation. The study examined this phenomenon prior to
      implementation of a California law that discourages such calls. METHODS:
      Concurrent data were collected for patients who presented to the ED and who had
      authorization calls made to their HMOs prior to their ED evaluations during the
      period September through December 1994. Data collected included: 1) the number of
      authorization calls made, 2) the frequency that ED care was deemed unnecessary by
      the HMO, 3) the outcomes of patients denied authorization, and 4) the time and
      personnel involved in completing calls. Follow-up phone calls were made to
      patients who left the ED after the HMO denied authorization for payment. RESULTS:
      The total ED census was 19,935 patient visits for the four-month period.
      Authorization calls were made for 4,642 (23%) of the ED visits. There were 545
      patients (12%) in this group who had authorization denied and only 29 (5%) chose
      to remain in the ED for continued evaluation. The total time required to complete
      a call ranged from 20 minutes to 2.6 hours. Authorization calls and denials
      caused the following problems: 1) patients for whom calls were made were subject
      to delays in ED care; 2) at least seven patients referred to HMO clinics were
      referred back to the ED because the patient was too sick to receive clinic care;
      3) patients were inconsistently asked to sign an against-medical-advice form when
      they chose to leave with unstable conditions; and 4) high-risk patients denied
      authorization included patients with final diagnoses of ectopic pregnancy, acute
      myocardial infarction, pulmonary embolus, respiratory failure, and sepsis.
      CONCLUSIONS: Calls for payment authorization prior to ED patient evaluation delay
      patient care and place some patients' health and safety in jeopardy.

PMID- 8881544
TI  - Evaluation of resident performance and intensive bedside teaching during direct
      observation.
AB  - OBJECTIVE: To describe the experience of a residency program in emergency
      medicine with an intensive observational evaluation of resident performance in
      the ED. METHODS: Each resident was directly observed and evaluated during a
      clinical shift four times each academic year: once by each residency codirector
      and twice by the resident's faculty advisor. The faculty members performed this
      evaluation outside of "clinical staffing time," shadowing the resident for
      several hours in the ED during the resident's assigned shift. The resident and
      assigned faculty member discussed the patients' histories and physical
      examination findings and developed treatment plans together. Prior to initiation
      of the observation, the faculty were provided with guidelines for the evaluation
      of specific skills. Immediate feedback of strengths and deficiencies was provided
      to the resident. RESULTS: Subjective evaluations by faculty suggest that new
      insights into resident clinical strengths and weaknesses were determined using
      this approach. Objective scoring of resident performance demonstrated
      heterogeneity of skills between residents as well as inconsistency of skills for
      specific residents. CONCLUSIONS: The program provided the faculty with protected
      teaching time, an opportunity to share clinical pearls, and unique insights into
      resident performance that are not obvious during standard clinical interactions.

PMID- 8881545
TI  - Managing law enforcement (K-9) dog bites in the emergency department.
AB  - OBJECTIVE: To review the types of injuries due to law enforcement (K-9) dog bites
      and address related management issues. METHODS: A case series of law enforcement
      dog bite victims is reported and related literature reviewed. RESULTS: Law
      enforcement dogs are taught a bite-and-hold technique for subduing individuals
      suspected of felony crimes. This bite-and-hold technique's greater applied force
      results in a unique spectrum of injuries, including deep puncture wounds, severe
      crush injuries, large tissue avulsions and lacerations, wounds necessitating
      surgical debridement, bony injuries ranging from cortical violations to displaced
      fractures, neurovascular damage, and other wounds at high risk for infection. The
      four reported cases highlight the types of injuries and complications associated
      with law enforcement dog bites. CONCLUSION: Attention to potential deep injuries
      of nerves, vessels, and the musculoskeletal system is essential with law
      enforcement dog bites. Injuries associated both with pursuit and arrest and with
      the bites themselves must be identified and assessed. Guidelines for the ED
      treatment of patients with law enforcement dog bite injuries are proposed.

PMID- 8881546
TI  - Is handwashing teachable?: failure to improve handwashing behavior in an urban
      emergency department.
AB  - OBJECTIVES: To assess handwashing frequency according to CDC recommendations; and
      to test a simple intervention to increase handwashing compliance, designed for
      the unique setting of the ED. METHODS: A prospective, observational, before-and
      after study design with a convenience sampling technique was used to assess
      handwashing compliance in the ED of a 742-bed urban, university-affiliated
      medical center with 65,000 visits annually. Emergency physicians (EPs),
      registered nurses (RNs), and nurse practitioners (NPs) were informed that their
      patient encounters were being monitored, but the nature of the study was kept
      confidential. A single observer evaluated individual EPs, RNs, and NPs in one-,
      two-, or three-hour blocks, recording compliance with CDC handwashing
      recommendations. After two weeks, brightly colored signs with CDC recommendations
      for handwashing were posted at all sinks and a copy of a related publication on
      handwashing by medical personnel was distributed to all staff. Handwashing
      behaviors were again observed. RESULTS: A total of 252 situations requiring
      handwashing were observed, 132 pre-intervention and 120 post-intervention. Total
      handwashing, handwashing by each staff designation, and handwashing in each CDC
      recommendation category--except handwashing between contacts with different
      patients--all showed tendencies toward improvement, though none was significant
      (p > 0.05). Both the NPs and RNs demonstrated significantly higher adherence to
      recommended handwashing between patients after the intervention than did the EPs
      (85% vs 71% vs 31%, p < 0.01 and p < 0.05, respectively). CONCLUSION: Despite a
      trend in improvement of compliance with CDC recommendations, handwashing among ED
      personnel remained unacceptably low.

PMID- 8881547
TI  - Level I trauma certification and emergency medicine resident major trauma
      experience.
AB  - OBJECTIVE: American College of Surgeons (ACS) and Residency Review Committee for
      Emergency Medicine (RRC-EM) guidelines conflict regarding the role of emergency
      physicians in directing major trauma resuscitations. This article describes the
      impact of ACS level I trauma certification on emergency medicine (EM) resident
      trauma experience. METHODS: A written survey and a follow-up letter were sent to
      all 101 EM program directors as of August 16, 1994. The survey addressed
      demographics and trauma experience at hospitals designated by the RRC-EM as
      primary training sites. RESULTS: There were 95 (94%) survey respondents.
      Estimates of the percentage of trauma resuscitations directed by EM residents
      were significantly lower at level I centers (52% +/- 27%, 95% CI 45-59%) than
      they were at non-level I centers (70% +/- 30%, 95% CI 58-82%) (p < 0.01). There
      was no significant difference in trauma census between level I and non-level I
      centers. Of 14 respondents who said they were cited by the RRC-EM for inadequate
      trauma experience, ten (71%) were in ACS level I trauma centers (p = 1.0). Twelve
      of the 14 respondents cited for inadequate trauma experience were in either the
      Northeast or the Midwest. CONCLUSIONS: EM residents direct a smaller percentage
      of major trauma resuscitations at ACS level I hospitals than they do at non-level
      I facilities. This finding is not offset by an increased trauma census at level I
      facilities and may be more pronounced in the Northeast and the Midwest.

PMID- 8881548
TI  - The efficacy of a standard training program for transillumination-guided
      endotracheal intubation.
AB  - OBJECTIVE: To evaluate the success rate, intubation time, and complication rate
      of transillumination-guided intubation following two hours of instruction in the
      use of the Trachlight (TL) device. METHODS: A prospective, randomized crossover
      laboratory trial was conducted at an emergency medical service training site with
      30 nonpaid volunteer paramedic students, one month prior to their graduation. The
      students were instructed in the use of the TL in a standardized curriculum
      consisting of didactic, video, and demonstration sessions. Each student was
      required to successfully intubate a training manikin with the TL five times.
      Approximately three weeks later, the students were asked to intubate the manikin
      20 times, alternating between direct laryngoscopy (DL) and TL. RESULTS: The
      success rates were 94% for DL and 63% for TL (p < 0.0001). The mean intubation
      times were 14.6 seconds for DL and 16.8 seconds for TL (p < 0.001). The
      incidences of trauma were 7.3% for DL and 1.4% for TL (p < 0.001). CONCLUSION: A
      two-hour training session, including five successful light-guided intubations
      using the TL, was inadequate for producing acceptable success rates during
      manikin intubations by paramedic students. While TL intubation intervals were
      shorter when successful, the 2.2-second difference was not clinically meaningful.
      The incidence of trauma in our manikin model during TL intubations was
      significantly lower than that with DL.

PMID- 8881549
TI  - Association of training level and short-term cosmetic appearance of repaired
      lacerations.
AB  - OBJECTIVE: To determine the association between emergency practitioner level of
      training and cosmetic appearance of primarily closed wounds as evaluated at the
      time of suture removal. METHODS: A retrospective analysis of wound registry data
      was performed. At the time of wound closure, standard data were collected
      including details of patient demographics, wound characteristics, preparation,
      closure, and postoperative care, for consecutive patients sutured in the ED.
      Follow-up data were obtained at the time of the return visit using a previously
      described cosmetic scale. With the scale, all lacerations were assigned 0 or 1
      point each for the presence or absence of six items: a step-off of borders;
      contour irregularities; margin separation; edge inversion; excessive distortion;
      and overall appearance. For analysis, the proportion of wounds with a score of 6
      (optimal cosmetic appearance in all categories) was associated with practitioner
      level of training. RESULTS: Five hundred fifty-two patients' wounds were
      evaluated. The percentages of various practitioners' achieving an optimal
      cosmetic score were: medical students (MSs), 50%; first-year residents (EM1s),
      54%; second-year residents (EM2s), 66%; third-year residents (EM3s), 68%;
      physician assistants (PAs), 70%; and attending physicians (APs), 66%. The senior
      practitioners (EM2s, EM3s, PAs, APs) were significantly more likely to obtain a
      maximal cosmetic score than were the junior practitioners (MSs, EM1s) (68% vs
      52%, p = 0.016). CONCLUSION: Significant improvement in short-term cosmetic
      results following wound repair is associated with a training level beyond PGY1.
      These data reinforce the need for careful patient selection and close supervision
      of wound repair by trainees, especially of wound repair by medical students and
      interns.

PMID- 8881550
TI  - Pediatric penile swelling.

PMID- 8881551
TI  - Comparison between emergency department and inpatient E-codes.

PMID- 8881552
TI  - Emergency medicine residency brochure on the Internet.

PMID- 8881553
TI  - [Cephalometric study of the pterygoid process linear parameters in the human
      adult and child].
AB  - A cephalometric investigation of the lateral plate of the pterygoid process was
      conducted in the sagittal, frontal and axial plane. The aim of this study was to
      make linears observations on the pterygoid process. A biostatistical method
      helped comparing the variations of the lateral pterygoid plate in relation to the
      variations of the basi-cranium and the face with special interest given to the
      mandible, because of its tight muscular connection to the pterygoid process.

PMID- 8881554
TI  - [Morphology of the basi-exoccipital synchondrosis during human growth].
AB  - The morphology of the basi-exoccipital synchondrosis has been studied in a series
      of 150 human skulls. This series consisted of 12 skulls of fetuses, 12 skulls of
      new-born children, 86 skulls of children and 40 skulls of adult subjects. The
      synchondrosis was composed of two plates: a principal vertical plate or basi
      exoccipital plate, and a accessory horizontal plate or hypoglossal prolongation.
      The exoccipital bone alone participated in the formation of the walls of the
      hypoglossal nerve's canal. In the first stages of development, the anterior wall
      of this canal was cartilaginous, formed by the posterior edge of the hypoglossal
      prolongation of the synchondrosis. The occipital condyle derived from the
      basioccipital and the exoccipital bones; the inferior edge of the basi
      exoccipital plate separated these two parts. The relative proportions of the
      anterior basioccipital part compared with the posterior exoccipital part varied
      from the fifth to the seventh of the total condyle area. The observations could
      have been arranged in six age groups presenting morphological similarities of
      development. At first, the hypoglossal processes of the exoccipital bone drew
      together (VI intra-uterine months to 1 year 6 months), then came into contact (1
      year 6 months to 2 years 6 months), and finally fused together (2 years 6 months
      to 4 years) realizing the bony continuity of the walls of the hypoglossal nerve's
      canal. The contact and finally the fusion between the basioccipital and
      exoccipital bones were then realized (4 years to 8 years). The entire fusion of
      the synchondrosis was completed between the ages of 6 and 8 years. The adult
      morphology was established at around 8 years of age.

PMID- 8881555
TI  - [Vascular networks of the periphery of the finger nail].
AB  - The vascular networks of the periphery of the nail of the finger are studied on
      fingers of adults, fetus and newborns, by injecting the vascular system with
      gelatinous Indian ink. The nail is an avascular horny structure, partially
      covered with the nail fold. It is lying on a nail bed which prolonges forwards
      with the hyponychium. Each part of the nail apparatus (nail fold, matricial and
      unmatricial parts of the nail bed, hyponychium) presents a characteristic network
      which is tributary of dorsal collaterals arising from the digital palmar vessels
      and from their arcades. These networks are papillar, pseudopapillar, reticular
      and subdermical. The morphology and density of these networks vary according to
      their localisation and are superimposed with the histological variations of the
      different parts of the nail apparatus. Thus the matricial part of the nail bed
      shows a poor vascularization. It corresponds to the germinative part of the nail
      and is responsible of the color of the lunula. The unmatricial part of the nail
      bed and the hyponychium have dense vascular networks with glomi.

PMID- 8881557
TI  - Acetylcholinesterase distribution in the central nervous system of the
      Megalobulimus oblongus (Gastropoda, Pulmonata).
AB  - The acetylcholinesterase (AChE) in the central nervous system (CNS) of the
      Megalobulimus oblongus was demonstrated by using Koelle and Friedenwald's
      procedure. The AChE positive reaction was revealed in the nervous cell bodies and
      processes in the different ganglia of the CNS. The largest number of strong
      positive neuronal subsets reside in pedal and buccal ganglia. Other positive cell
      bodies are also located in clusters in the left portion of the visceral ganglion,
      meso and postcerebrum, and pleural ganglia. In some neurons the enzymatic
      reaction only appeared at trophospongium level. The neuropilian synaptic areas
      also exhibited AChE reactivity. These data provide further evidence that AChE is
      present in neuronal bodies of the CNS of this pulmonate snail, and in some areas
      is probably involved in cholinergic circuits.

PMID- 8881556
TI  - [Venous vascularization of the lentiform nucleus].
AB  - The venous vascularization of the nucleus lentiformis in man is studied in 30
      brains by injecting the vascular system with gelatinous Indian ink. The venous
      vascularization of the nucleus lentiformis is drained towards the deep venous
      system of the brain by two ways, one ascending, the other descending. The first
      one is formed by superior lenticular veins which drain into the thalamo-striate
      vein, principal tributary of the internal cerebral vein. The second one is formed
      by inferior lenticular veins which depend from the deep middle cerebral vein,
      another tributary of the internal cerebral vein. The veins of the nucleus
      lentiformis, especially the veins of the putamen, present many similarities with
      these one of the cerebral cortex. They form the center of venous units surrounded
      by an arterial ring formed by the branches of ramification of the central
      arteries. The principal vein of the unit is surrounded by a capillary-free space.
      This similarities may be explained by the common origin of the cerebral cortex
      and of the putamen, both belong to the neocortical system.

PMID- 8881558
TI  - "In vitro" expression of the cardiogenic potentiality of chick embryo heart
      forming cells.
AB  - Chick embryos between final presomitic and 4 somites stage were studied. The
      subcephalic fold was handly severed from the embryos and cultivated in liquid
      medium for 7 days. Because of the embryo age, no heart anlage was observed at the
      moment of dissection. After 4 hours of culture the cells began to migrate from
      the explants. After 20 hours a very extended migration ring was observed in all
      of the cultures; in the explants, one or more newformed tubular or spherical
      masses of cells throbbed rhythmically. Their size and shape were related to the
      embryos age: from presomitic embryos, irregular clusters appeared, while starting
      from two somites embryos tubular, vascular-like structures were formed. The cells
      of the throbbing areas at submicroscopic observation showed organizing
      myofibrillar apparatus into the cytoplasm; junctional complexes between the cells
      and gap junctions in course of organization were present in the vascular-like
      structures. This suggests that very early, in the lateral mesoderm are the
      presumptive cardiac cells which can develop "in vitro" as myocardic elements even
      in absence of the interactions that occur during the development "in vitro"; the
      observed vascular-like structures may be considered as an attempt to form a sort
      of cardiac primordium "in vitro", and a further step in the expression of the
      cardiogenic potentiality, involving cell-cell communications. The serial sections
      of the embryos enhanced that into the cultivated areas, vessels from yolk sac are
      always present; this suggests that the vascular structures, i.e. the endothelium
      may be involved in the determination of the myocardic elements.

PMID- 8881559
TI  - Double heterozygosity of chromosomal inversion in mice: a key to speciation.
AB  - Inversion can be very efficient as a reproductive barrier when the same
      chromosomes are involved in two different rearrangements leading to a double loop
      during the pachytene stage. The consequence can be a strongly reduced fertility
      of the double heterozygotes, leading to an irreversible dichotomy.

PMID- 8881560
TI  - [Articles published in the Archives d'Anatomie, d'Histologie et d'Embryologie
      from volume 1 (1922) to volume 74 (1991-92)].
AB  - Three anatomists followed one another as Chief Editor of the Archives: Professor
      A. Forster (Strasbourg) from volume 1 (1922) to volume 29 (1940), Professor G.
      Winckler (Lausanne) from volume 40 (1957) to volume 53 (1970), and Professor J.
      G. Koritke (Strasbourg) from volume 54 (1971) to volume 74 (1991-92). From the
      outset, the Archives received papers from distinguished French and foreign
      anatomists. The Archives also constitute, since their origin, one of the
      preferential organs of expression for the Strasbourgian morphological works. All
      fields of morphology are represented. All zoological groups are concerned, some
      Invertebrates, but principally Vertebrates: Fishes, Amphibia, Reptiles, Birds,
      and Mammals amongst which the human species occupies a priviliged place. A total
      of 938 papers has been published in the Archives. Most papers are in French (833
      i.e. 89.0%). Papers in English (89 i.e. 9.5%) are more numerous in the most
      recent volumes; other papers are in Italian (11 i.e. 1.0%) and in German (5 i.e.
      0.5%).

PMID- 8881562
TI  - Proceedings of the Physiological Society. King's College London meeting, December
      18-20, 1995. Abstracts.

PMID- 8881561
TI  - [History of histology in Strasbourg].
AB  - Since the cellular theory was formulated in 1839, the University of Strasbourg
      has held a pioneer place in histology. This new morphological science has had,
      since its origin, close relations with physiology, and from 1846 to 1871, an
      original histophysiological school was organized in Strasbourg. The microscope
      and the study of tissues were considered as a fundamental approach for the
      progress of biological and medical knowledge. After the German annexation of
      Alsace, the scientists from this school participated in the renewal of histology
      in Nancy, Montpellier, and Paris. In 1872, when the new German university was
      created, an anatomical institute regrouped all aspects of normal morphology:
      anatomy, histology, and embryology. This was the case until 1918. In 1919, when
      the Faculty of Medicine was reorganized after Alsace was restored to France, a
      specific chair and institute of histology were created. This was the beginning of
      a school of histophysiology which was internationally renowned in the rise of
      experimental endocrinology. Great discoveries followed one after another:
      folliculin in 1924 and demonstration of the duality of ovarian hormones, the
      prominent place of the anterior part of the hypophysis and the demonstration of
      prolactin in 1928, thyreostimulin in 1929, then study of the other stimulins. In
      1946 a chair and institute of medical biology were created. In 1948, a service of
      electron microscopy was opened. D.A. Lereboullet (1804-1865), E. Kuss (1815
      1871), C.B. Morel (1822-1884), J.A. Villemin (1827-1892), M. Duval (1844-1907),
      G. Schwalbe (1844-1916), P. Bouin (1870-1962), M. Aron (1892-1974), J. Benoit
      (1896-1982), R. Courrier (1895-1986) et M. Klein (1905-1975), were among the
      famous scientists who worked in histology in Strasbourg.

PMID- 8881563
TI  - [New hepatitis viruses].

PMID- 8881564
TI  - [Does a healthy carrier of hepatitis C exist?].

PMID- 8881565
TI  - [Fulminant or sub-fulminant hepatocellular failure caused by metastatic
      invasiveness of the liver: an other cause of hypoxic hepatitis?].
AB  - OBJECTIVES: The purpose of this retrospective study was to report a series of 9
      new cases of fulminant hepatic failure due to metastatic liver disease and to
      identify signs to support a theory of hypoxia. METHODS: In these 9 cases and in
      38 previously published cases of fulminant or subfulminant liver failure, we
      looked for clinical (shock, sepsis, and cutaneous signs of circulatory failure),
      laboratory (marked increase in serum aminotransferases levels) and histological
      (cell necrosis) parameters compatible with liver hypoxia. RESULTS: Cutaneous
      signs of circulatory failure or shock were observed in 3 of the 9 cases in this
      study, and were not due to cardiogenic or septic shock. A marked increase in
      serum aminotransferases levels, 10 times above the upper limit of normal, was
      observed in 8 of the 9 cases in the present study and in 23 of 37 cases of the
      literature. Liver cell necrosis was observed in 6 of the 7 autopsied patients in
      this series and in 20 of 34 cases in the literature. Generally, liver cell
      necrosis was more severe than tumor cell necrosis and was related to the degree
      of sinusoidal involvement by tumoral cells. In one case, hepatic blood flow was
      decreased despite a high level of cardiac blood flow suggesting impairment of
      circulation in the liver. CONCLUSIONS: These 9 cases and a review of the
      literature support the hypothesis of hypoxic liver cell necrosis leading to acute
      liver failure in cases of metastatic liver disease. However, liver hypoxia cannot
      explain all the reported cases and was never due to circulatory failure from
      cardiac or septic causes, but to the sinusoidal involvement by tumor cells.

PMID- 8881566
TI  - High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case
      control study.
AB  - OBJECTIVES AND METHODS: Extrahepatic manifestations have been reported in
      hepatitis C virus infection. To assess the relationship between diabetes mellitus
      and hepatitis C virus, we studied 152 patients with chronic hepatitis C and 152
      controls hospitalized during the same period with hepatitis B virus (n = 51) or
      alcohol-induced (n = 101) liver diseases matched for age, sex, and the presence
      of cirrhosis (prevalence: 58%). Patients with jaundice, ascites, encephalopathy,
      prothrombin activity < 65%, or serum albumin < 35 g/L were excluded. RESULTS:
      Diabetes, defined by fasting serum glycemia > 1.4 g/L on at least two separate
      occasions or previously treated overt diabetes, was present in 38 patients with
      chronic hepatitis C (24%) and in 13 patients in the control group (9%, P <
      0.002). In the 51 diabetic patients, irrespective of serum anti-hepatitis C virus
      status, 41 (81%) had non insulin dependent diabetes and 45 (88%) had cirrhosis.
      Family history of diabetes or obesity was observed in 2 (5%) of the diabetic
      patients with chronic hepatitis C and in 6 (46%) of the diabetic controls (P =
      0.002). Plasma C-peptide (855 +/- 448 pmol/L versus 1,152 +/- 491 pmol/L, NS) and
      insulin levels (83 +/- 40 pmol/L versus 184 +/- 86 pmol/L, NS), assayed in 17
      diabetic patients with chronic hepatitis C and in 9 diabetic controls, were lower
      in the former. The prevalence of HLA B8, DR3 or DR4 antigens, which was searched
      for in 77 patients with chronic hepatitis C, was not different in diabetic and
      non diabetic patients, and, was similar to the reference population. Serum islet
      cell antibodies were found in 5 patients with chronic hepatitis C (3 with
      diabetes) and in 2 controls. CONCLUSION: Diabetes mellitus is more prevalent in
      patients with chronic hepatitis C than in patients with other liver diseases, and
      usually occurs in the absence of predisposing factors. These results suggest a
      role of hepatitis C virus infection in the pathogenesis of diabetes.

PMID- 8881567
TI  - [Mechanism of action of ursodeoxycholic acid in cholestatic liver diseases].

PMID- 8881568
TI  - [Upper endoscopy, sedation and anesthesia: what needs? what conditions?].

PMID- 8881569
TI  - [Conditions of practice of upper digestive endoscopy in ambulatory care. Results
      of a national survey (I)].
AB  - OBJECTIVES: The aim of the study was to describe the usual conditions of practice
      of esophagogastroscopy in ambulatory care by French gastroenterologists. METHODS:
      During a week, a questionnaire was filled out for each esophagogastroscopy
      performed in ambulatory or day care. RESULTS: Seven hundred and thirty nine
      gastroenterologists participated in the study (25.9% of French
      gastroenterologists) and enrolled 4585 patients. Intra-venous sedation was
      performed in 36.6% of endoscopic examinations, with diazepam (17.8%), midazolam
      (41.7%), propofol (14.9%), diazepam and propofol (2.1%) or midazolam and propofol
      (23.5%). A morphinomimetic was associated in 58.6% of cases. Monitoring equipment
      of endoscopy units was: aspiration (58.6%), pulse oxymeter (41.6%),
      electrocardiographic monitoring (37.7%). Recommendations about follow-up after
      ambulatory anaesthesia were not implemented in 7.3% of examinations with
      anaesthesia (patient discharged alone). Seventeen minor adverse events were
      recorded. CONCLUSION: The study underlines variability of practice, mainly about
      use of sedation, monitoring and follow-up of patients during esophagogastroscopy
      performed in ambulatory care in France. An improvement in quality of endoscopy
      practice is likely.

PMID- 8881570
TI  - [Patient's opinion following an upper digestive endoscopy in ambulatory care.
      Results of a national survey (II)].
AB  - OBJECTIVES: The aim of the study was to evaluate patient satisfaction after
      esophagogastroscopy performed in ambulatory care and to correlate it with
      conditions of usual practice. METHODS: Study was proposed to the French
      gastroenterologists. During a week, 2 questionnaires were filled out for each
      esophagogastroscopy performed in ambulatory care: one recorded conditions of
      examination and one was independently filled out by the patient one day after
      endoscopy. RESULTS: Seven hundred and thirty nine gastroenterologists and 4,585
      patients participated in the study. Among the patients, 3,758 (82%) filled out
      the questionnaire. Sedation was performed in 36.6% of cases. Subsequent endoscopy
      would be accepted by 79.3% of patients in the same conditions. Acceptance was
      significantly better with use of sedation and use of propofol. Without sedation,
      independent factors associated with a better acceptance were: male gender,
      absence of habitual benzodiazepine medication, endoscopy performed in private
      practice or private hospitals, smaller size of endoscope. CONCLUSION: This study
      underlines factors associated with a good acceptance of esophagogastroscopy
      without sedation and could help to improve decision-making regarding use of
      sedation.

PMID- 8881571
TI  - [Role of 5-HT3 receptors in the control by cholecystokinin of transient
      relaxations of the inferior esophageal sphincter in dogs].
AB  - AIMS: The aim of this study was to determine, using specific antagonists, whether
      5-HT3 receptors participate in triggering transient lower esophageal sphincter
      relaxations, independently or in relation with their CCKergic control. METHODS:
      Esophageal, lower esophageal sphincter and fundus pressure were manometrically
      monitored in 5 conscious dogs. Gastric distensions with air at constant pressure
      (1.0 and 1.7 kPa) were performed during 30 min under IV infusion of CCK8S (0.5
      microgram/kg/h) or NaCl 9/1000 and were preceded (10 min) by IV administration of
      5-HT3 receptors antagonists (ondansetron 0.2-500 micrograms/kg and granisetron
      100 micrograms/kg) or NaCl 9/1000. RESULTS: The number of transient relaxations
      induced by a 1.7 kPa gastric distension (7.9 +/- 0.4/30 min) was dose-dependently
      reduced by ondansetron (1-100 micrograms/kg) and by granisetron (100
      micrograms/kg). Ondansetron (100 micrograms/kg) did not modify the number of
      relaxations under a 1.0 kPa gastric pressure (2.7 +/- 0.4 vs 2.6 +/- 0.4/30 min)
      but reduced the increase of the occurrence of relaxations induced by CCK8S under
      a gastric pressure of 1.0 and 1.7 kPa. CONCLUSION: These results suggest that the
      CCK control in triggering transient lower esophageal sphincter relaxations is
      modulated by serotonin via 5-HT3 receptors subtypes.

PMID- 8881572
TI  - [Targeting of type IV carbonic anhydrases in Capan-1 human pancreatic duct cells
      is concomitant of the polarization].
AB  - Carbonic anhydrases II and IV play an essential role in the synthesis and
      secretion of HCO3- ions in pancreatic duct cells. Secretion of these ions is
      regulated by the CFTR (cystic fibrosis transmembrane conductance regulator)
      chloride channel. In the present study, the expression of carbonic anhydrases IV
      and their targeting to plasma membranes were examined during the growth of human
      pancreatic duct cells in vitro. Human cancerous pancreatic duct cells of Capan-1
      cell line which polarize during their growth were used. We show that: a) these
      cells express carbonic anhydrases IV continuously during growth in culture, and
      the expression depends on the stage of growth and the conformation of the cells;
      b) carbonic anhydrases IV are seen in the cytoplasm in non-polarized cells, but
      become progressively anchored to plasma membranes as the cells polarize, being
      targeted to the apical membranes of polarized cells; c) the subcellular
      distribution of carbonic anhydrases IV indicates that these enzymes are
      synthetized in rough endoplasmic reticulum and then transported towards the
      plasma membrane using the classical secretory pathway through the Golgi
      apparatus. The results indicated that targeting of carbonic anhydrases IV in
      Capan-1 cells is linked to cellular polarization.

PMID- 8881573
TI  - [Cardiospasm: dilatation or celioscopy?].

PMID- 8881574
TI  - [Prolonged clinical remission of cholangitis in early human immunodeficiency
      virus infection after surgical biliary derivation].
AB  - During the acquired immunodeficiency syndrome, most cases of cholangitis develop
      at an advanced stage of disease. We report a case of cholangitis in a 47-year-old
      homosexual man, stage IIa according to Center of Disease Control classification.
      An isolated jaundice was the first manifestation of the disease. The number of
      CD4 was 380/microL. Ultrasonography and endoscopic retrograde cholangiography
      showed a 7 cm stenosis of the common bile duct, and cystic duct stenosis, with
      associated intra-hepatic biliary duct dilatation. No infectious agent was found.
      Cholecystectomy and hepaticojejunostomy were performed. Pathological examination
      of liver biopsy and a sample of the resected common bile duct was consistent with
      sclerosing cholangitis. The postoperative course was uneventful. During a three
      year follow-up period, the patient was disease free but he suddenly died of
      uncontrolled bleeding from duodenal ulcer. In HIV-infected patients, surgical
      treatment can be performed in case of symptomatic long stenosis of the common
      bile duct.

PMID- 8881575
TI  - [Clinical and radiological aspects of tuberculous splenic abscesses. Presentation
      of 3 cases].
AB  - Tuberculous splenic abscess is an exceptional disease with silent presentation in
      disseminated tuberculosis infection. Imaging procedures allow to suspect this
      diagnosis in case of multilocular nodules of the spleen, or unilocular
      pseudotumoral macronodule. We report three cases of tuberculous splenic abscesses
      in two patients with acquired immunodeficiency syndromes and one with
      polycythemia vera. Under antituberculous treatment, clinical evolution was good
      with regression of the radiological features.

PMID- 8881576
TI  - [Treatment with octreotide of stenosing cystic dystrophy on heterotopic pancreas
      of the duodenal wall].
AB  - Cystic dystrophy of the duodenal wall developing in heterotopic pancreas is a
      rare disease. Weight loss and painless vomiting due to duodenal stenosis where
      the main clinical manifestations of this entity in a chronic alcoholic patient.
      Diagnosis was made by using an ultrasonic-endoscope equipped with a miniprobe.
      Although surgical treatment is usually recommended in this situation, the
      clinical condition of this patient improved dramatically after subcutaneous
      injections of somatostatin analog (octreotide). This treatment was maintained
      during 9 months and no recurrence was observed during the follow-up period.

PMID- 8881577
TI  - [Acute hepatitis caused by the combination of tiliquinol and tilbroquinol
      (Intetrix)].

PMID- 8881578
TI  - [Acute painful and febrile hepatic involvement related to ingestion of
      tianeptine].

PMID- 8881579
TI  - [Acute mixed hepatitis caused by tianeptine].

PMID- 8881580
TI  - [Acute cholecystitis with gallbladder perforation treated by transpapillary
      endoscopic drainage].

PMID- 8881581
TI  - [Tamoxifen and hepatocellular carcinoma: verdict after enthusiasm...].

PMID- 8881582
TI  - [Severe forms of Mallory-Weiss syndrome].

PMID- 8881583
TI  - [Herpetic esophagitis disclosing primary HIV infection].

PMID- 8881584
TI  - [Gastric MALT lymphoma and Helicobacter pylori].

PMID- 8881585
TI  - [Escherichia coli O157:H7 ischemic colitis with hemolytic-uremic syndrome].

PMID- 8881586
TI  - [Annual meeting of the Swiss Society of Cardiology and annual meeting of The
      Swiss Society of Infection. Zurich, 21-23 March 1996. Abstracts].

PMID- 8881587
TI  - [64th annual meeting of the Swiss Society of Internal Medicine and annual meeting
      of the Swiss Society of Hematology. Zurich, 21-23 March 1996. Abstracts].

PMID- 8881588
TI  - Influence of the nature of carbohydrate intake on the absorption chronology of
      reducing sugars and volatile fatty acids in the pig.
AB  - The results of three successive experiments were compared in order to analyse the
      chronology of absorbed energy amounts resulting from enzymatic or microbial
      digestion, respectively. These experiments were undertaken in the pig to study
      the absorption kinetics of reducing sugars and amino-nitrogen formed during
      enzymatic digestion and of volatile fatty acids (VFA) formed through the action
      of the digestive flora. The animals were given well-balanced semi-synthetic diets
      containing poorly digestible or indigestible carbohydrates. These diets contained
      the following ingredients: (Experiment A) purified cellulose at two levels of
      incorporation (LC diet 6%, HC diet 16%); (Experiment B) alfalfa meal (22%)
      supplying 6% crude fibre (HA diet) versus lactose (22%) with an addition of 6%
      purified cellulose (HL diet); (Experiment C) sorbitol in the form of maltitol
      (53%) with an addition of 6% purified cellulose (SHyd diet) versus maltose under
      the same conditions (53%, SNat diet). Each diet was fed to five pigs fitted with
      catheters placed in the portal vein and carotid artery and with a flow probe
      around the portal vein, which made it possible to study the nutrient absorption
      after one meal (800 g). Under our experimental conditions (intake: 2 200-2 300
      kcal, except HC 1 930 kcal) the higher level of crude fibre or the presence of
      osides in the diet which are poorly digestible in the small intestine (lactose,
      maltitol), depressed the absorption of reducing sugars (RS) (amount absorbed
      within 12 h relative to intake %: SNat 92.8; LC 82.7; HL 78.7; HA 76.0; HC 72.5;
      SHyd 71.3). The absorbed energy supply resulting from the VFA increased
      accordingly, in the presence of poorly digestible or indigestible carbohydrates
      (as a percentage of the total energy absorbed as RS, lactic acid (LA) and VFA:
      SNat 3.4; LC 7.1; HL 8.9; HC 10.4; SHyd 13.1) with one exception (HA: 6.0%). For
      all diets, the greatest energy absorption (42-63% according to the diet) occurred
      during the first 4 h after the meal, the larger fraction resulting from RS (86.8
      94.8% according to the diet). The energy supply due to the absorption of VFA
      became large between the 5th and the 12th hour, and was larger for diets
      containing poorly digestible or indigestible carbohydrates (as a percentage of
      the total RS + LA + VFA: SNat 6.5; LC 8.7; HC 14.3; HC 14.4; SHyd 23.3) with one
      exception (HA: 9.0%). Although the late absorption of VFA was insufficient to
      compensate for the energy deficit due to a lower of RS, it may bridge the energy
      gap during the interprandial period.

PMID- 8881589
TI  - Fertility of ram spermatozoa pellet-frozen in zwitterion-buffered diluents.
AB  - The fertility (positive ultrasound scanning 60-75 days after insemination) of ram
      spermatozoa frozen in Tris- or zwitterion/glucose/egg yolk/glycerol-based
      diluents was examined during the natural breeding season (autumn). In Experiment
      1 Tris-citrate, high glucose and Hepes-NaOH diluents were used and ewes (n = 266)
      were inseminated (induced oestrus) with 20 (uterus) or 180 (cervix) million
      motile spermatozoa. There was no difference in fertility (range: 10.9-71.1%)
      between diluents, despite the superior post-thawing motility and progressive
      velocity of spermatozoa in Hepes-NaOH compared with the other diluents (P <
      0.001). In Experiment 2, there was no difference in fertility (range: 4.1-50.0%)
      between Tris-citrate and Hepes-NaOH diluents after insemination (induced oestrus)
      of ewes (n = 290) with 10 (uterus) or 100 (cervix) million motile spermatozoa,
      respectively. In Experiment 3 Tris-citrate, Hepes-NaOH and Pipes-NaOH diluents
      were used and ewes (n = 492) were inseminated (natural oestrus) with 8 or 24
      (uterus), or 80 or 240 (cervix) million motile spermatozoa. There were no
      differences in fertility (range: 35.4-52.9%) between insemination doses or
      diluents despite the superior motility and acrosome integrity in the zwitterion
      compared with the Tris-citrate diluents (P < 0.001). In all experiments, the
      fertility of frozen spermatozoa was higher for intrauterine than cervical
      insemination (51.9 vs 22.1%, n = 1 048; P < 0.01). It was concluded that post
      thawing in vitro quality was superior and the fertility comparable after freeze
      thawing spermatozoa in zwitterion compared with Tris-citrate diluents.

PMID- 8881590
TI  - Effect of a high sulfur diet on rumen microbial activity and rumen thiamine
      status in sheep receiving a semi-synthetic, thiamine-free diet.
AB  - A semi-synthetic thiamine-free diet was used on weaned lambs to test the effect
      of a high sulfur level on the rumen, microbial activity and on the microbial
      production of thiamine. In vivo and in vitro kinetic studies, as well as the
      determination of the thiamine concentrations and thiaminase activity in the
      rumen, were performed during the 16 week experiment. A high sulfur level (0.6%)
      in the diet, in comparison with a normal sulfur level (0.2%), did not modify the
      microbial activity of the rumen with the exception of a slightly retarded
      decrease in the volatile fatty acid (VFA) rumen concentration. The rumen thiamine
      level and the thiaminase activity were not modified by the dietary sulfur level.
      In contrast, the rate of sulfate reduction into sulfide in the rumen increased
      progressively with the 0.6% sulfur diet. In conclusion, a high sulfur level
      (0.6%) in the diet of sheep did not modify the thiamine status of the rumen. It
      strongly increased the production of sulfides but an adaptation period of several
      weeks was required by the rumen microflora to reduce sulfate at a maximal rate.

PMID- 8881591
TI  - Identification of hyaluronic acid and chondroitin sulfates in human follicular
      fluid and their effects on human sperm motility and the outcome of in vitro
      fertilization.
AB  - This study measured glycosaminoglycans (GAGs) in human follicular fluid (hFF)
      obtained from patients undergoing hormonal stimulation with combined GnRH agonist
      followed by gonadotropin hormone (hMG or FSH) for in vitro fertilization (IVF).
      The GAGs were partially characterized through the use of various
      mucopolysaccharidases and then their effects tested on human sperm motility. In
      hFF, the GAG and protein concentrations were 4.4 +/- 1.3 mg/L and 32.6 +/- 3.2
      g/L respectively. Chondroitins (CS) and hyaluronic acid (HA) significantly
      stimulate sperm motion in comparison to the control. The oocytes inseminated with
      GAGs-pretreated spermatozoa showed a significantly higher rate of cleavage and
      pregnancy or delivered number. The present results suggest that hFF is a rich
      source of sulfated glycosaminoglycan (CS), and non-sulfated glycosaminoglycan
      (HA). The stimulatory effects of hFF on human sperm motility may well depend on
      CS and HA. GAGs pretreated sperm may enhance the fertilizing ability of
      spermatozoa and thus the IVF outcome.

PMID- 8881592
TI  - Influence of pH on lipolysis and biohydrogenation of soybean oil by rumen
      contents in vitro.
AB  - The effect of different pH values on rumen lipolysis and biohydrogenation was
      investigated during incubations of the rumen contents with 40 or 80 mg of soybean
      oil as the sole substrate. Mean pH values studied were 6.8, 6.3, 6.0, 5.6 and
      5.2. Lipolysis was calculated from the decrease in fatty acids present in
      triacylglycerols (TAG), as well as from the accumulation of free fatty acids
      (FFA) during the incubation. At pH < or = 6.0 lipolysis was low, and the
      inhibition became greater with decreasing pH. At the same pH value, the
      inhibition in incubations with 80 mg of soybean oil was more pronounced than with
      40 mg. Even at the lowest pH value, after incubation, no free linolenic acid
      could be detected because of biohydrogenation, whereas linoleic acid
      hydrogenation was only partially inhibited at pH 5.2. This means that lipolysis
      is much more sensitive to low pH values than biohydrogenation. Literature data
      indicate however that, besides pH, other factors must be involved in the decrease
      of both lipolysis and biohydrogenation in the rumen of animals fed highly
      concentrated diets.

PMID- 8881593
TI  - Effect of a specific aromatase inhibitor on oestradiol secretion by porcine
      corpora lutea at various stages of the luteal phase.
AB  - The present study was undertaken to investigate the aromatization capability of
      pig corpora lutea at different stages of the luteal phase using the nonsteroidal
      aromatase inhibitor CGS 16949A. Luteal cells were collected during early (0-2
      days after ovulation), mid- (7-10 days after ovulation) and late (13-16 days
      after ovulation) luteal phase. Cells were incubated either with or without 10(-7)
      MT (testosterone-supplemented culture). Six hours after starting the cultures,
      0.1, 0.5 or 1.0 microM aromatase inhibitor was added to both culture types for
      the next 12 h period. Addition of the aromatase inhibitor to the luteal cells
      isolated during the early luteal phase had no effect on basal and testosterone
      supplemented oestradiol secretion. The aromatase inhibitor added to cells
      isolated during the mid- and late luteal phase, however, caused a significant
      decrease in the basal and testosterone-stimulated secretion of oestradiol. This
      supports the hypothesis that luteal cells from these stages have active
      aromatase. The highest aromatization potential was observed in regressing corpora
      lutea. Oestradiol secreted by the regressing corpora lutea could play an active
      role in the regulation of oestrus cycle and could have a possible endocrine
      influence on gonadotropin secretion, a paracrine action on follicular growth or
      an autocrine influence on the luteal activity.

PMID- 8881594
TI  - Hepatic and renal D-amino acid oxidase activities in the growing rat after ten
      days of protein undernutrition and refeeding.
AB  - The activity levels of hepatic and renal D-amino acid oxidase (EC 1.4.3.3), a key
      enzyme for D-amino acid utilization in mammals, were determined in growing rats
      after a 10 day period of protein undernutrition and subsequent refeeding.
      Reducing the protein intake for 10 days (3% casein diet) resulted in an 8% loss
      of the animals' mean body weight and a 50% decrease in the mean size of the liver
      and kidney as compared to the control animals fed on a 22% casein diet during the
      same period. When the undernourished rats were refed with the normal protein
      diet, their weight increased about four fold as compared with that of the control
      animals, and after a ten day period of refeeding, the lost body and tissue
      weights were completely recovered. As far as the specific activity of D-amino
      acid oxidase was concerned, a 44% reduction took place in the liver of rats
      subjected to protein undernutrition for 10 days. During the period of refeeding,
      however, the enzyme activity level increased slowly in comparison with the
      overall hepatic protein level, since its specific activity on day 10 was still
      28% below that of the control rats. In sharp contrast, no significant change in
      the kidney enzyme level was observed throughout these nutritional manipulations.
      This study strongly suggests that the synthesis and/or catabolism of D-amino acid
      oxidase may depend on the dietary protein content of the liver but not on that of
      the kidney. This suggests that D-amino acid oxidase may possibly play distinct
      physiological roles in these two body organs.

PMID- 8881595
TI  - Modulation of the feeding response of lactating dairy cows to peripheral insulin
      administration with or without a glucose supply.
AB  - The aim of this study was to determine the effect of physiological amounts of
      insulin without glucoprivation on food intake of dairy cows. Four multiparous
      Holstein cows at 150 days post-partum were allocated to the treatments,
      consisting of a 4 h intravenous infusion of: 1) control (saline); 2) insulin
      (3.41 micrograms/kg); 3) glucose (2.75 mmol/kg); and 4) insulin plus glucose
      (same dosage). A complete diet was offered ad libitum and the intake behaviour
      was continuously recorded. The plasma insulin was only slightly increased during
      the insulin treatment, but the treatments including glucose increased it more.
      The insulin treatment increased dry matter intake during infusion (+12%; P <
      0.07), but the increase was offset during the following 4 h. In contrast, dry
      matter intake was slightly decreased by insulin during the first hour of infusion
      (-8%; P < 0.03) when the insulin-induced hypoglycemia was prevented by a
      concomitant infusion of glucose. The insulin-induced glucoprivation stimulated
      food intake, whereas glucose availability had no obvious satiating effect in
      dairy cows.

PMID- 8881596
TI  - Polyunsaturated fatty acids status in blood, heart, liver, intestine, retina and
      brain of newborn piglets fed either sow milk or a milk replacer diet.
AB  - Docosahexaenoic (DHA) and arachidonic acids (20:4n-6) are deposited in large
      amounts in the developing neural tissues of the fetus and neonate. The suckling
      infants receive both fatty acids via the maternal milk, whereas formula-fed
      infants must synthesize them de novo from their respective precursors, linoleic
      (18:2n-6) and alpha-linolenic (18:3n-3) acids. We compared the lipid status of 14
      and 21-day-old piglets fed either natural milk or infant formula, with special
      emphasis on the resulting DHA and 20:4n-6 levels in the neural tissues. The two
      diets presented similar ratios of precursors (18:2n-6/18:3n-3 = 14-16). The sow
      milk contained 20:4n-6 (0.6% of total fatty acids) and very low levels of DHA (<
      0.1%). Formula feeding resulted in higher deposition of DHA in the brain than sow
      milk feeding, whereas the brain content of 20:4n-6 was not altered. The brain DHA
      level was negatively correlated with the 18:2n-6/18:3n-3 ratio in the red blood
      cells (RBC). In contrast, it was not correlated with the DHA concentration in the
      circulating lipids. The results indicate that the very low amount of DHA in sow
      milk has no effect on the accumulation of DHA in the piglet's brain, and that
      natural milk and formula are not equivalent with respect to precursor bio
      availability and processing. This difference could be the result of a higher
      absorption rate and/or the metabolic sparing of formula 18:3n-3. The data support
      the view that the balance between the essential precursors in the circulating
      lipids is of vital importance for optimal deposition of DHA in the developing
      neural tissues.

PMID- 8881597
TI  - Nitric oxide and parasitic disease.

PMID- 8881598
TI  - Molecular approaches to the diagnosis of onchocerciasis.

PMID- 8881599
TI  - The evolution of life history strategies in parasitic animals.

PMID- 8881600
TI  - Malarial parasites of lizards: diversity and ecology.

PMID- 8881601
TI  - Salmonella enteritidis phage type 21b.

PMID- 8881602
TI  - General outbreaks of infectious intestinal disease in England and Wales 1992 to
      1994.
AB  - Data from the surveillance scheme of general outbreaks of infectious intestinal
      disease in England and Wales, reported to the PHLS Communicable Disease
      Surveillance Centre (CDSC), were used to review 1280 of the 1594 outbreaks
      identified between 1 January 1992 and 31 December 1994 for which a minimum data
      set was captured. The number of outbreaks reported in each regional health
      authority ranged from 31 in Mersey to 221 in Yorkshire. The commonest pathogens
      reported were salmonellas in 32% (412) of outbreaks, small round structured virus
      (SRSV) in 27% (342), Clostridium perfringens in 7% (90), and Shigella sonnei in
      4% (46). The main mode of transmission was described as foodborne in 50% (642),
      over half of which were caused by salmonellas, and person to person in 39% (496),
      over half of which were caused by SRSV. Most outbreaks transmitted from person to
      person occurred in hospitals and in residential institutions for elderly people.
      Outbreaks lasted from one to 217 days (median five days) and their duration
      varied with the pathogen. The median attack rate was 37%. Illness was reported in
      34,158 people, 751 of whom (2%) were admitted to hospital. There were 55 deaths,
      28 of which were associated with salmonella and 12 with SRSV. Most of the
      outbreaks reported and the associated morbidity and mortality could have been
      prevented by following standard food hygiene practices, implementing infection
      control policies, and ensuring that food entering kitchens was of the highest
      microbiological quality possible.

PMID- 8881603
TI  - Salmonella in retail poultry in Northern Ireland.
AB  - A prospective survey was carried out in Northern Ireland between February and
      August 1994 to assess the current levels of salmonella in retail chickens, and to
      determine whether contamination rates differed between chickens sold in
      supermarkets and by butchers. One hundred and forty chilled and frozen raw
      chickens were sampled from retail display and examined for the presence of
      salmonella using an approved method. Contamination was commoner in chickens that
      were chilled, sold from smaller premises, and reared or slaughtered outside
      Northern Ireland. Salmonella enteritidis phage type 4 was the most commonly
      isolated type. The contamination rate of about 7% is considerably lower than in
      Great Britain and this may partially explain the lower rate of human salmonella
      infections in Northern Ireland. This finding supports the recommendations made in
      the Advisory Committee on the Microbiological Standards of Food's report on
      poultry meat, since many of the improvements proposed are already in operation in
      areas of the Northern Ireland poultry industry.

PMID- 8881604
TI  - Bodybuilders, raw egg drink, and Salmonella enteritidis.

PMID- 8881605
TI  - The health of women and children in South Carolina: success or crisis?

PMID- 8881606
TI  - Maternal mortality in South Carolina: an update 1985-1994.

PMID- 8881607
TI  - Preventing HIV infection in infants and children by reducing perinatal HIV
      transmission: review of efficacy and preliminary cost evaluation. South Carolina
      Pediatric AIDS Advisory Committee.

PMID- 8881608
TI  - Maternal use of alcohol during pregnancy is a risky lifestyle.
AB  - Alcohol is a well known teratogen. Its role in causing fetal alcohol
      syndrome/fetal alcohol effects is well documented. A vast amount of study over
      the past several decades has finally provided insight into many aspects of its
      effect. The only effective treatment is complete abstinence from the drug during
      pregnancy.

PMID- 8881609
TI  - The role of health care in child abuse and neglect prevention.
AB  - In this review, we have suggested a variety of ways that we as health care
      providers can adapt our practices to provide the support necessary to increase
      the competency of families in parenting and nurturing their young. There are a
      variety of modalities worthy of consideration as methods that make the lives of
      our children that much better. In our quest to prevent child maltreatment, we
      need an emphasis on supporting families so that they can effectively provide the
      love and nurturing that all children require.

PMID- 8881610
TI  - Managed care and early discharge.

PMID- 8881611
TI  - Maternal and child health.

PMID- 8881612
TI  - Transoesophageal echocardiography in anaesthesia and intensive care.

PMID- 8881613
TI  - Single bolus compared with a fractionated dose injection technique of bupivacaine
      for extradural Caesarean section: effect on uteroplacental and fetal haemodynamic
      state.
AB  - We studied 26 healthy parturients undergoing elective Caesarean section,
      allocated randomly to receive extradural block with 0.5% plain bupivacaine in a
      double-blind manner in either a single bolus or fractionated doses. After a 3-ml
      test dose, an additional 20 ml of bupivacaine were given over a 5-min period in
      the single bolus group (n = 13) and over a 25-min period in the fractionated dose
      group (n = 13). We studied the effects of bupivacaine on blood flow velocities in
      the maternal placental and non-placental uterine and fetal umbilical arteries
      before and four times during establishment of extradural block using a pulsed
      colour Doppler technique. Median sensory block reached T3 in the single-dose
      group compared with T4 in the fractionated-dose group. Two subjects in each group
      required i.v. ephedrine to correct transient hypotension (systolic arterial
      pressure < 90 mm Hg). Blood flow velocity waveform indices of the uterine and
      umbilical arteries did not differ significantly within or between groups during
      the study. There was no significant difference in neonatal outcome, as assessed
      by Apgar scores and umbilical artery pH values. In conclusion, we observed no
      deterioration in uteroplacental circulation after administration of a single
      bolus dose of bupivacaine.

PMID- 8881614
TI  - Spinal anaesthesia with 0.25% hyperbaric bupivacaine for Caesarean section:
      effects of volume.
AB  - To investigate the safety and efficacy of 0.25% hyperbaric bupivacaine for spinal
      anaesthesia in Caesarean section, we studied 60 parturients allocated randomly to
      one of three groups. According to the patient's height, groups 1, 2 and 3
      received 3.2-3.6 ml (8-9 mg), 3.6-4.0 ml (9-10 mg) and 4.0-4.4 ml (10-11 mg) of
      0.25% bupivacaine in 5% glucose, respectively. Subarachnoid injection was
      performed in the right lateral decubitus position, and parturients were then
      turned immediately supine with left uterine displacement. Mean spread of sensory
      analgesia was significantly higher in group 3 (T2-3) than in groups 1 and 2 (T4-5
      in each group). Duration of sensory analgesia was significantly longer in groups
      2 and 3 than in group 1. Complete motor block of the lower extremities occurred
      in all patients but in only one in group 1. Onset time and duration of motor
      block were not significantly different between the three groups. The incidence of
      hypotension was significantly higher in group 3 (75%) than in groups 1 and 2 (40%
      in each group). The efficacy of intraoperative analgesia was significantly
      greater in groups 2 and 3 than in group 1. The incidence of patients requiring
      analgesics during operation was significantly lower in groups 2 (25%) and 3 (10%)
      than in group 1 (70%). There was no difference in neonatal condition between the
      three groups. Spinal anaesthesia with 3.6-4.0 ml of 0.25% bupivacaine in 5%
      glucose was satisfactory for Caesarean section.

PMID- 8881616
TI  - Soft tissue anatomy within the vertebral canal in pregnant women.
AB  - To clarify pregnancy-induced changes in soft tissue anatomy within the vertebral
      canal, we have studied magnetic resonance (MR) images of the lumbar spine in
      three women. In each subject, T2-weighted axial MR images were obtained both
      before pregnancy and at 32 weeks' gestation, and the paired images were compared.
      The extradural venous plexus was engorged significantly in supine parturients. In
      addition, the engorged extradural venous plexus displaced the dura away from the
      wall of the vertebral canal in a posterior direction, which resulted in a
      decrease in the volume of the cerebrospinal fluid in the dural sac. These
      findings confirmed the long-held concept that the engorged extradural venous
      plexus in supine parturients decreases the effective capacity of the extradural
      and subarachnoid spaces.

PMID- 8881615
TI  - Spinal anaesthesia for Caesarean section: effect of Sprotte needle orientation.
AB  - We induced spinal anaesthesia in 100 women presenting for elective Caesarean
      section with the mother in the right lateral position. Patients were allocated
      randomly to have the side eye of the 24-gauge Sprotte spinal needle pointing in
      one of four directions: group A, cephalad; group B, right lateral; group C, left
      lateral; group D, caudad. Isobaric bupivacaine 0.5% (2.5 ml) was injected over 30
      s before the mother was placed supine with a 15 degree left lateral tilt. Onset
      time and height of the subsequent analgesic and anaesthetic blocks were assessed
      by a blinded observer. Onset of sensory block to T4 was significantly faster in
      group A (P = 0.001). There were no differences in final block height, incidence
      of hypotension, nausea and vomiting or ephedrine requirements.

PMID- 8881617
TI  - Thrombelastography changes in pre-eclampsia and eclampsia.
AB  - We have measured platelet count, bleeding time and thrombelastography (TEG)
      variables and the correlation between these variables in 49 pregnant patients
      presenting with pre-eclampsia or eclampsia. Eighteen patients (37%) had a
      platelet count < or = 150 x 10(9) litre-1 and seven (14%) had a platelet count <
      or = 100 x 10(9) litre-1. Bleeding time was prolonged > 9.5 min in 13 (27%)
      patients and the TEG was abnormal in four (8%). The TEG variables, k time and
      maximum amplitude (MA) had a strong correlation with platelet count (k time
      platelet count < or = 150 x 10(9) litre-1, r = -0.68, P = 0.003, platelet count <
      or = 100 x 10(9) litre-1, r = -0.84, P = 0.02; MA--platelet count < or = 150 x
      10(9) litre-1, r = 0.72, P = 0.001, platelet count < or = 100 x 10(9) litre-1, r
      = 0.78, P = 0.04). There was no correlation between bleeding time and
      thrombocytopenia (platelet count < or = 150 x 10(9) litre-1, r = -0.18, ns;
      platelet count < or = 100 x 10(9) litre-1, r = 0.09, ns). There was no
      correlation between bleeding time and any measured TEG variable. Of the 10 (20%)
      patients with an adequate platelet count (> 100 x 10(9) litre-1) but prolonged
      bleeding time, the TEG was normal, suggesting adequate haemostasis. An MA of 53
      mm, which is the lower limit for normal pregnancy, correlated with a platelet
      count of 54 x 10(9) litre-1 (95% confidence limits 40-75 x 10(9) litre-1).
      Although the number of patients with severe thrombocytopenia was small, a
      platelet count of 75 x 10(9) litre-1 should be associated with adequate
      haemostasis.

PMID- 8881618
TI  - Alfentanil-mediated analgesia during propofol injection: no evidence for a
      peripheral action.
AB  - We have investigated if alfentanil acts via peripheral opioid receptors to
      relieve the pain which occurs on injection of propofol. Thirty seconds before
      induction of anaesthesia and immediately after a tourniquet at 50 mm Hg greater
      than systolic pressure was inflated on the upper arm, patients were given either
      placebo (n = 22), alfentanil 1 mg (n = 22) or lignocaine 40 mg (n = 22) via an
      i.v. cannula in the dorsum of the hand. Pain during injection of propofol was
      assessed using a three-point verbal rating scale, recorded at 8-s intervals. We
      found a significant reduction in pain after lignocaine compared with the two
      other groups (P < 0.001), but there was no difference between the placebo and
      alfentanil groups. We conclude that alfentanil does not relieve pain on injection
      with propofol via an action on peripheral opioid receptors when alfentanil is
      limited to the forearm for 30 s before induction of anaesthesia.

PMID- 8881619
TI  - Psychophysical and electrophysiological responses to experimental pain may be
      influenced by sedation: comparison of the effects of a hypnotic (propofol) and an
      analgesic (alfentanil).
AB  - Sedation may influence the responses of some experimental pain models used to
      test analgesic efficacy. In this study we compared the effects of a sedative
      (propofol) and analgesic (alfentanil) on: nociceptive reflex to single and
      repeated electrical stimulations; mechanical pressure pain; and evoked potentials
      elicited by nociceptive (electrical and laser) and non-nociceptive (acoustical)
      stimulation. We studied 12 healthy volunteers with two subanaesthetic
      concentrations of propofol and two analgesic concentrations of alfentanil. Both
      propofol and alfentanil increased the threshold for nociceptive reflex to single
      electrical stimulations, but only alfentanil increased the threshold for
      nociceptive reflex to repeated electrical stimulations. The pressure pain
      tolerance thresholds were increased significantly by alfentanil, whereas propofol
      significantly decreased the thresholds (hyperalgesia). Propofol and alfentanil
      induced similar reductions in the amplitudes of the evoked potentials elicited by
      nociceptive (electrical and laser) and non-nociceptive (acoustical) stimulation,
      whereas only alfentanil reduced the perceived pain to nociceptive stimulations.
      We have shown that sedation can influence both the psychophysical and
      electrophysiological responses of some experimental pain tests used to measure
      analgesic efficacy, and that propofol in subhypnotic doses, has no analgesic
      effect on painful electrical and heat stimulations, but has a hyperalgesic effect
      on mechanical pressure pain.

PMID- 8881620
TI  - Quantitative EEG in assessment of anaesthetic depth: comparative study of
      methodology.
AB  - Methodology for assessment of depth of anaesthesia based on analysis of the
      electroencephalogram (EEG) is controversial. Techniques range from display of
      single measures, for example median value of the frequency spectrum, to dedicated
      pattern recognition systems based on measures of several EEG features. We have
      compared the performance of four techniques using tape-recorded data from 23
      patients anaesthetized with either halothane or isoflurane using standardized
      regimens. The techniques were: (1) median frequency, (2) spectral edge frequency,
      (3) the cerebral function analysing monitor (CFAM1) and (4) a depth of
      anaesthesia monitor based on EEG pattern recognition (ADAM). Dose-response curves
      are presented for stepwise increases in stable end-tidal concentrations of each
      agent. Results indicated considerable inter-patient variability and the
      limitations of single EEG measures, particularly with deeper anaesthesia
      producing a burst suppression pattern in the EEG. Pattern recognition techniques
      reduced these difficulties and appeared to be promising over a wide range of
      anaesthetic levels.

PMID- 8881621
TI  - Spectral edge frequency of the electroencephalogram to monitor "depth" of
      anaesthesia with isoflurane or propofol.
AB  - To determine threshold values, sensitivity and specificity of the spectral edge
      frequency (SEF) of the electroencephalogram (EEG) that indicate intraoperative
      movements, we studied 49 patients undergoing, elective laparotomy. Extradural
      analgesia was used in all patients. To maintain general anaesthesia, patients in
      group 1 (n = 23) received 0.4-1.2 vol% isoflurane and patients in group 2 (n =
      24) propofol 3-5 mg kg-1 h-1 i.v. During operation and emergence from
      anaesthesia, spontaneous purposeful movements were documented. The EEG was
      recorded continuously in the awake state until the end of anaesthesia. Power
      spectral analysis calculated the SEF and power in the delta, theta, alpha and
      beta bands and the delta ratio. Adequate anaesthesia caused a statistically
      significant decrease in SEF from 16 to 12 Hz. Power in the beta band decreased
      and power in the theta band and total power increased compared with the awake
      state. Before and during movements observed in the intraoperative period or
      during emergence from general anaesthesia, SEF increased from 12 to 18 Hz, the
      power in beta band increased and theta power decreased compared with the state of
      adequate anaesthesia. A threshold value of SEF 14 Hz to predict movements during
      anaesthesia had a sensitivity of 72% and specificity of 82%.

PMID- 8881622
TI  - The reinforced laryngeal mask airway for dento-alveolar surgery.
AB  - We have evaluated the reinforced laryngeal mask airway (LMA) for use during dento
      alveolar surgery in 100 ASA I and II day-case patients allocated randomly to
      receive either a nasotracheal tube or reinforced LMA. We recorded ease of airway
      insertion, airway complications, quality of recovery and replies to a 24-h
      postoperative questionnaire. In addition, a fibreoptic assessment was made of
      laryngotracheal soiling, and the effect of head movement and the position of the
      reinforced LMA. There were no significant differences in difficulty in airway
      positioning or perioperative oxygen desaturation. Nineteen patients in the
      nasotracheal tube group had epistaxis (P = 0.001) and laryngotracheal soiling
      occurred in three of these patients. Two reinforced LMA were dislodged on moving
      into the operating theatre and in a further five patients in this group there was
      partial airway obstruction (compared with none in the nasotracheal tube group; P
      = 0.018) which was caused by downward pressure on the mandible by the surgeon.
      There were no differences in postoperative complications. No surgeon reported
      poor access to the operating field. Overall the reinforced LMA provided
      satisfactory conditions for this surgery but vigilance of the airway was
      required, especially at the time of extraction.

PMID- 8881623
TI  - Isoflurane waste gas exposure during general anaesthesia: the laryngeal mask
      compared with tracheal intubation.
AB  - We have compared exposure to isoflurane while using the laryngeal mask airway
      (LMA) during anaesthesia under positive pressure ventilation with exposure while
      using tracheal intubation. Trace concentrations of isoflurane were measured
      directly using a highly sensitive photoacoustic infrared spectrometer (Bruel and
      Kjaer 1302, Denmark) during general anaesthesia in 20 eye surgery procedures.
      Measurements were made at six locations (three personnel-related, three leakage
      related) in the operating theatre. Despite some high isoflurane values (greater
      than 2000 ppm at one leakage-related measurement point) all measured values at
      the personnel-related points were low (the majority were less than isoflurane 2
      ppm). In the LMA group, mean trace concentrations were slightly higher than in
      the tracheal tube (ET) group. Mean exposure to isoflurane, expressed as median
      (range) related to anaesthetic administration, was highest for the auxiliary
      nurse (0.64 (0.22-26.89) ppm for the LMA compared with 0.31 (0.02-1.07) ppm for
      the tracheal tube), followed by the anaesthetist (0.50 (0.28-2.28) ppm for the
      LMA compared with 0.35 (0.02-0.73) ppm for the tracheal tube) and the surgeon
      (0.36 (0.20-3.93) ppm for the LMA compared with 0.29 (0.01-0.50) ppm for the
      tracheal tube). We conclude that the use of the LMA in patients undergoing
      ventilation is not associated necessarily with high concentrations of isoflurane
      in a modern working environment.

PMID- 8881624
TI  - Ventilatory effects of eltanolone during induction of anaesthesia: comparison
      with propofol and thiopentone.
AB  - We recorded the ventilatory effects of eltanolone 0.75 mg kg-1, propofol 2.5 mg
      kg-1 and thiopentone 4 mg kg-1 at induction of anaesthesia in 76 unpremedicated
      patients, aged 18-65 yr. Measurements were made using a pneumotachograph
      incorporated between a close-fitting face mask and a T-piece delivering 35%
      oxygen. Eltanolone caused significantly less apnoea than propofol (incidence 57%
      vs 100%) and less reduction in ventilation than propofol (median maximum decrease
      4.8 vs 7.8 litre min-1), but the differences between eltanolone and thiopentone
      were smaller and generally not significant. Ventilatory frequency was maintained
      well in the eltanolone group.

PMID- 8881625
TI  - Effect of anaesthesia on lung function in children with asthma.
AB  - Spirometry was performed before operation, soon after recovery ("early") and the
      day after ("late") general anaesthesia for elective surgery in 20 children with
      asthma and 20 matched children without asthma. Pulse oximetry was recorded on the
      first postoperative night. The mean early peak expiratory flow rate (PEFR)
      decreased in the asthmatics by 19.91 (95% confidence intervals (CI) 10.84-28.97)%
      and in the controls by 19.25 (10.70-27.80)%. The mean early FEV1 decreased in the
      asthmatics by 16.02 (9.29-22.75)% and in the controls by 11.03 (2.86-19.19)%. The
      mean late decrease from baseline PEFR for the asthmatics was 18.55 (11.23-25.87)%
      but only 14.93 (7.89-21.97)% for the controls. The mean late FEV1 was 8.2 (0.83
      15.56)% below baseline in the asthmatics but only 6.82 (-0.79 to 14.42)% in the
      controls. There were no differences in overnight pulse oximetry. We conclude that
      healthy children exhibited a decrease in FEV1 and PEFR after general anaesthesia
      for elective surgery, but this decline did not appear to be any greater in well
      controlled asthmatic children compared with children who did not have asthma.

PMID- 8881626
TI  - Ketamine and norketamine plasma concentrations after i.v., nasal and rectal
      administration in children.
AB  - It has been suggested that nasal administration of ketamine may be used to induce
      anaesthesia in paediatric patients. We have examined the pharmacokinetics of
      ketamine and norketamine after nasal administration compared with rectal and i.v.
      administration in young children. During halothane anaesthesia, 32 children, aged
      2-9 yr, weight 10-30 kg, were allocated randomly to receive ketamine 3 mg kg-1
      nasally (group IN3) or ketamine 9 mg kg-1 nasally (group IN9); ketamine 9 mg kg-1
      rectally (group IR9); or ketamine 3 mg kg-1 i.v. (group IV3). Venous blood
      samples were obtained before and up to 360 min after administration of ketamine.
      Plasma concentrations of ketamine and norketamine were measured by gas liquid
      chromatography. Statistical comparisons were performed using ANOVA and the
      Kruskall-Wallis test, with P < 0.05 as significant. Mean plasma concentrations of
      ketamine peaked at 496 ng ml-1 in group IN3 within 20 min, 2104 ng ml-1 in group
      IN9 within 21 min, and 632 ng ml-1 in group IR9 within 42 min. Plasma
      concentrations of norketamine peaked at approximately 120 min after nasal
      ketamine, but appeared more rapidly after rectal administration of ketamine and
      were always higher than ketamine concentrations in the same situation. Calculated
      bioavailability was 0.50 in groups IN3 and IN9 and 0.25 in group IR9. We conclude
      that nasal administration of low doses of ketamine produced plasma concentrations
      associated with analgesia, but using high doses via the nasal route produced high
      plasma concentrations of ketamine similar to those that induce anaesthesia.
      However, the large volume of ketamine required was partly swallowed and led to an
      unacceptable variability of effect that precludes this route for induction of
      anaesthesia.

PMID- 8881627
TI  - Determinants of duration of ICU stay after coronary artery bypass graft surgery.
AB  - Prediction of duration of a patient's stay in the ICU after cardiac surgery is
      difficult. In 652 consecutive adult patients undergoing elective coronary artery
      bypass graft (CABG) surgery, we analysed prospectively preoperative and immediate
      postoperative variables thought to influence duration of stay in the ICU. With
      univariate analysis, we found that age, preoperative left ventricular ejection
      fraction, bypass time, aortic cross-clamp time, blood transfusions and the number
      of inotropic agents administered in the immediate postoperative period (for at
      least 6 h) were significant correlates of duration of stay in the ICU. However,
      logistic regression analysis showed that the number of inotropes was the most
      important determinant of stay in the ICU, with an overall prediction accuracy of
      94.8%. The main cause of prolonged stay in the ICU (more than 2 days) was low
      cardiac output syndrome. We conclude that analysis of perioperative variables
      enhanced our ability to accurately predict duration of stay in the ICU in cardiac
      surgery patients. The number of inotropic agents administered during the first 6
      h after operation was the most important determinant of duration of stay in the
      ICU.

PMID- 8881628
TI  - Comparison of propofol and a propofol-methohexitone mixture for induction of day
      case anaesthesia.
AB  - We studied 99 patients undergoing day-case urological surgery, allocated randomly
      to receive a sleep dose of either 1% propofol or a mixture of equal volumes of 1%
      propofol and 0.5% methohexitone, and thereafter a standardized anaesthetic. With
      the exception of minor differences in intraoperative heart rate there were no
      significant differences between the two groups in induction properties and
      complications, intraoperative variables, rate of recovery or postoperative
      sequelae.

PMID- 8881629
TI  - ASA classification and perioperative variables as predictors of postoperative
      outcome.
AB  - In a prospective study of 6301 surgical patients in a university hospital, we
      examined the strength of association between ASA physical status classification
      and perioperative risk factors, and postoperative outcome, using both univariate
      analysis and calculation of the odds ratio of the risk of developing a
      postoperative complication by means of a logistic regression model. Univariate
      analysis showed a significant correlation (P < 0.05) between ASA class and
      perioperative variables (intraoperative blood loss, duration of postoperative
      ventilation and duration of intensive care stay), postoperative complications and
      mortality rate. Univariate analysis of individual preoperative risk factors
      demonstrated their importance in the development of postoperative complications
      in the related organ systems. Estimating the increased risk odds ratio for single
      variables, we found that the risk of complication was influenced mainly by ASA
      class IV (risk odds ratio = 4.2) and ASA class III (risk odds ratio = 2.2). We
      conclude that ASA physical status classification was a predictor of postoperative
      outcome.

PMID- 8881630
TI  - Time course of increased haemodilution in hypotension induced by extradural
      anaesthesia.
AB  - Volume loading with crystalloid solution results in more pronounced haemodilution
      in patients who develop arterial hypotension during induction of extradural
      anaesthesia than in those who remain normotensive. The aim of this study was to
      describe the time course of this increase in haemodilution. Heart rate, systolic
      arterial pressure and blood haemoglobin concentration were measured every 3 min
      during the onset of extradural anaesthesia in 22 elderly men undergoing short
      urological operations. Fluid therapy consisted of 15 ml/kg body weight of
      Ringer's acetate solution. Patients with a decrease in systolic pressure of > 25%
      retained 50% (SD 12%) of the infused fluid in the circulation, while the others
      retained 36 (8%) (P < 0.002). In both groups, arterial hypotension was followed
      by increased haemodilution after a delay of as much as 15 min. This suggests
      that, despite volume loading, there is relative hypovolaemia throughout the
      development of hypotension.

PMID- 8881631
TI  - Combination of inhaled nitric oxide with i.v. nitroglycerin or with a
      prostacyclin analogue in the treatment of experimental pulmonary hypertension.
AB  - We have studied the effect of combining inhaled nitric oxide (NO) with an i.v.
      vasodilator agent, nitroglycerin, or ciloprost, a prostacyclin analogue, during
      acute pulmonary hypertension in pigs, induced by continuous infusion of a
      thromboxane analogue (U46619), adjusted to maintain mean pulmonary artery
      pressure (MPAP) at 40 mm Hg. The effects of the different treatments on MPAP and
      pulmonary resistances were determined. In the first part of the study, we
      determined the dose-response to increased NO concentrations from 5 to 40 ppm.
      This showed a maximum pulmonary effect with NO 5 ppm, but with no systemic
      effects. The effect of NO 10 ppm was then compared with two i.v. drugs.
      Nitroglycerin was less effective than NO on pulmonary vessels but induced
      significant arterial hypotension. Pulmonary vasodilatation induced by ciloprost
      was greater than that by NO but with the same side effects as nitroglycerin on
      systemic variables. We also found that the combination of NO and nitroglycerin
      had the same pulmonary effects as NO 10 ppm but that adding ciloprost to NO
      decreased pulmonary pressures significantly more than either drug used alone. We
      conclude that inhaled NO may be usefully combined with i.v. ciloprost but not
      with i.v. nitroglycerin.

PMID- 8881632
TI  - Role of prostaglandins and nitric oxide on halothane-induced arteriolar
      dilatation in rat diaphragm.
AB  - The effects of anaesthetics on the microcirculation of the diaphragm are
      incompletely understood. Therefore, we assessed by in vivo intravital microscopy
      in rats the action of halothane on diaphragmatic arteriolar diameter and the role
      of nitric oxide and prostaglandins on halothane-induced diaphragmatic arteriolar
      diameter. We studied 54 rats anaesthetized with thiopentone. Dose-response curves
      to topically applied Krebs' solution saturated with halothane at increasing
      concentrations of 0%, 1%, 3% and 5% were carried out in the presence of an
      inhibitor of nitric oxide synthesis (N omega-nitro-L-arginine (LNA), 300 mumol
      litre-1) or inhibitors of prostaglandin synthesis (mefenamic acid 20 mumol litre
      1 or indomethacin 20 mol litre-1) or in the absence of any inhibitor. We found
      dose-dependent arteriolar dilatation which was abolished by mefenamic acid and
      indomethacin. In contrast, the effect of halothane was not modified by LNA. These
      data demonstrated that halothane-induced arteriolar dilatation in the diaphragm
      of the rat was mediated by prostaglandins but not by nitric oxide.

PMID- 8881633
TI  - Ketamine inhibits nitric oxide production in mouse-activated macrophage-like
      cells.
AB  - We have investigated the effects of ketamine on nitric oxide produced by
      activated macrophages using a murine macrophage-like cell line, J774. Cells were
      incubated for 18 h under stimulation with lipopolysaccharide and interferon-gamma
      or lipoteichoic acid and interferon-gamma, with various concentrations of
      ketamine (6-600 mumol litre-1). Nitric oxide production was assessed by measuring
      nitrite, a stable by-product of nitric oxide breakdown, in the medium. Other N
      methyl-D-aspartate receptor antagonists, MK-801 (150 mumol litre-1) and
      dextromethorphan (150 mumol litre-1) were also tested. In addition, we studied
      the effects of ketamine on production of tumour necrosis factor-alpha by
      activated macrophages. Ketamine inhibited nitrite production dose-dependently
      with both lipopolysaccharide- and lipoteichoic acid-activated macrophages by up
      to approximately 65% at the highest ketamine concentration (600 mumol litre-1).
      Neither MK-801 nor dextromethorphan had an inhibitory effect. Ketamine also
      suppressed production of tumour necrosis factor-alpha. The data show that
      ketamine inhibited nitric oxide production by activated macrophages probably, in
      part, via inhibition of production of tumour necrosis factor-alpha, an autocrine
      stimulatory factor for nitric oxide production, but not via the NMDA receptor
      pathway, which is involved in neuronal nitric oxide production.

PMID- 8881634
TI  - Potentiation of local lignocaine-induced sensory block by calcium channel
      blockers in rats.
AB  - We have studied the effects of three different types of calcium channel blockers
      (verapamil, diltiazem, and nicardipine) on local lignocaine sensory block. The
      standardized tail flick test was used to measure the duration and degree of
      lignocaine-induced conduction block in rats. After obtaining baseline tail flick
      latencies (mean 3.2 s), two 100-microliter doses of 0.3% lignocaine alone, a
      combination of verapamil 25, 100 or 200 micrograms, diltiazem 25, 100 or 200
      micrograms, or nicardipine 0.5, 1.0 or 2.0 micrograms, and a large dose of
      calcium channel blockers (verapamil 200 micrograms, diltiazem 200 micrograms or
      nicardipine 2.0 micrograms) were injected on opposite sites of the tail base and
      the tail flick test was performed every 5 min for 45 min. A large dose of the
      calcium channel blockers showed no prolongation of tail flick latencies.
      Administration of 0.3% lignocaine alone produced a significant increase in tail
      flick thresholds and the peak effect of the percentage maximum possible effect (%
      MPE) was demonstrated at 5 min after drug injection (mean % MPE 28.8%; P < 0.01
      vs baseline). Co-administration of 0.3% lignocaine and three doses of verapamil
      produced significant increases in area under the curve (AUC) in a dose-dependent
      fashion. Mean AUC values for 0.3% lignocaine alone and a combination of verapamil
      25, 100 or 200 micrograms were 217.5, 502.5, 529.1 and 1600.3, respectively.
      Almost similar patterns of augmentation in AUC values were demonstrated after
      addition of different doses of diltiazem or nicardipine to 0.3% lignocaine. We
      conclude that the use of mixtures of local anaesthetic and calcium channel
      blocker potentiated lignocaine sensory block at the level of the peripheral
      nerves.

PMID- 8881635
TI  - I.v. anaesthetic agents inhibit dihydropyridine binding to L-type voltage
      sensitive Ca2+ channels in rat cerebrocortical membranes.
AB  - Previous studies have implicated the neuronal L-type voltage-sensitive Ca2+
      channel (VSCC) as a target site for i.v. anaesthetic agents. It is unclear if
      these agents interact with the L-channel alpha-subunit 1,4-dihydropyridine (DHP)
      binding site. In this study, we have examined the interaction of thiopentone,
      pentobarbitone, ketamine, etomidate, propofol and alphaxalone, and the non
      anaesthetic barbiturate, barbituric acid, with the DHP binding site on rat
      cerebrocortical membranes. Binding assays were performed in 1-ml volumes of Tris
      HCl 50 mmol litre-1, pH 7.4, for 90 min at room temperature containing 200
      micrograms of membrane protein with [3H]PN200-110 as a radiolabelled DHP. Non
      specific binding was defined in the presence of nifedipine 10(-5) mol litre-1.
      The interaction of i.v. anaesthetics was determined by displacement of [3H]PN200
      110 0.2 nmol litre-1. All i.v. anaesthetics showed some interaction with the DHP
      binding site. The concentrations of anaesthetic producing 25% inhibition of
      specific binding (corrected for the competing mass of [3H]PN200-110), K25 were
      (mumol litre-1): thiopentone 48 (SEM 2), pentobarbitone 95 (7), propofol 40 (2),
      etomidate 25 (2), alphaxalone 17 (3) and ketamine 198 (16). Barbituric acid was
      ineffective. With the exception of ketamine, there was a significant correlation
      between K25 and peak serum concentration during anaesthesia (P = 0.033) and serum
      concentrations on wakening (P = 0.018), suggesting that the L-channel DHP binding
      site may be a target for i.v. anaesthetic agents.

PMID- 8881636
TI  - Is inhibition of dopamine uptake relevant to the hypnotic action of i.v.
      anaesthetics?
AB  - We have examined the effects of ketamine, etomidate, propofol and thiopentone on
      the uptake of [3H]-dopamine into rat striatal synaptosomes. [3H]-dopamine uptake
      (5 min, 37 degrees C) was potently inhibited by nomifensine, a classical
      inhibitor of the dopamine carrier. All anaesthetics induced concentration-related
      inhibition of the uptake process, values for IC50 being 4.6 x 10(-6), 5.5 x 10(
      5), 1.5 x 10(-4) and 2.7 x 10(-4) mol litre-1 for ketamine, etomidate, propofol
      and thiopentone, respectively. For all anaesthetics, inhibition of [3H]-dopamine
      uptake was reversible with a non-competitive profile. These data suggest that
      inhibition of striatal dopamine uptake may represent a relevant target site for
      some, but not all, i.v. anaesthetics.

PMID- 8881637
TI  - Myocardial extraction of bupivacaine in anaesthetized sheep and by hearts of
      sheep and rats in vitro.
AB  - We observed the in vivo kinetics of bupivacaine in the cardiopulmonary system,
      particularly in the pulmonary artery, the upper part of the descending aorta and
      the coronary sinus of anaesthetized sheep, each of which received a high dose
      infusion into the central vein. In some experiments dilution curves were
      monitored for the non-extracted dye, indocyanine green. Concentrations of
      bupivacaine were approximately 20% lower in the aorta than in the pulmonary
      artery. This gradient of bupivacaine was present across the lung for 5-10 min.
      Concentrations of bupivacaine in the coronary venous plasma were also markedly
      lower than at the arterial site. Initially more than 50% of the amount of
      bupivacaine at the arterial site was removed by the heart. Later, the myocardial
      extraction ratio decreased and plateaued at a value of 0.30-0.40. At this time,
      concentrations of bupivacaine in the pulmonary artery were approximately 12
      micrograms ml-1. Therefore, approximately 0.3-0.6 mg of bupivacaine were
      extracted per minute by the sheep heart in vivo. On the other hand, isolated
      perfused rat hearts did not substantially remove bupivacaine (2 micrograms ml-1)
      from the medium. Approximately one-third of 14C-bupivacaine was retained in
      slices of rat and sheep myocardial tissue. However, there was no evidence that
      metabolism played a substantial role in the cardiac kinetics of bupivacaine.

PMID- 8881638
TI  - Nitrous oxide produces a non-linear reduction in thiopentone requirements.
AB  - We studied 88 healthy, ASA I patients (aged 20-45 yr), to determine if nitrous
      oxide affects thiopentone requirements for achieving 50% probability of no
      movement in response to verbal commands (CP,50). Patients were allocated randomly
      to one of four nitrous oxide concentration groups (0%, 20%, 40% and 60%).
      Patients in each group were also allocated randomly to receive predetermined
      target plasma concentrations of thiopentone. Computer-controlled continuous
      infusion was used to maintain the target plasma thiopentone concentration, and
      this concentration was held constant for 6 min to ensure equilibration. The
      CP,50, value of thiopentone in the absence of nitrous oxide was 14.8 micrograms
      ml-1. The reduction in CP,50 by nitrous oxide was non-linear, and the interaction
      coefficient between nitrous oxide and thiopentone was significantly smaller than
      zero (P = 0.0274), indicating that nitrous oxide antagonized the ability of
      thiopentone to prevent response to verbal commands.

PMID- 8881639
TI  - Evaluation of two warming systems after cardiopulmonary bypass.
AB  - We have compared the Thermomat electric undermattress (JMW Systems, Edinburgh,
      UK) and the Bair Hugger (Augustine Medical, Courtelary, Switzerland) forced-air
      warming blanket in 30 adult patients after cardiac surgery. All patients were
      warmed to an oesophageal temperature of 38 degrees C before termination of
      cardiopulmonary bypass (CPB); those with oesophageal temperatures < 35.5 degrees
      C at skin closure were allocated randomly to be rewarmed in the intensive care
      unit either on the Thermomat (n = 15) or under the Bair Hugger blanket (n = 15),
      at their highest settings. Oesophageal and lateral thigh skin temperatures were
      recorded every 15 min for 4 h. There was a significantly faster increase in core
      temperature (0.5 vs 0.75 degrees C h-1; P < 0.0002) and skin temperature (0.86 vs
      1.3 degrees C h-1; P < 0.001) in the Bair Hugger group. However, there was no
      difference in the number of patients who reached a core temperature of 36 degrees
      C (15 Bair Hugger, 14 Thermomat) or 37 degrees C (11 Bair Hugger, seven
      Thermomat), or in the number of patients who reached a skin temperature of 37
      degrees C in 4 h (four Bair Hugger, one Thermomat). Twelve patients in the Bair
      Hugger group reached a skin temperature of 36 degrees C compared with two in the
      Thermomat group (P < 0.001). The Bair Hugger warmed faster than the Thermomat
      both centrally and peripherally, and warmed more patients to a core temperature
      of 37 degrees C in 4 h, but did not reduce the time to tracheal extubation or
      alter important clinical aspects of postoperative course.

PMID- 8881640
TI  - Calcium homeostasis during i.v. infusion of 1.5% glycine in anaesthetized pigs.
AB  - We have examined changes in plasma concentrations of calcium in seven
      anaesthetized pigs during i.v. infusion of irrigating fluid containing 1.5%
      glycine. Volumes infused were 875 ml at 20 min (22 ml kg-1), 1475 ml at 40 min
      and 2075 ml at 60 min (75 ml kg-1). Plasma concentrations of sodium decreased
      from 134.5 (SD 3.4) to 112.8 (6.7) mmol litre-1 at 60 min and correlated with the
      volume of glycine infused (r2 = 0.73; P < 0.0001). Changes in total calcium
      concentrations were not statistically significant. A decrease in ionized calcium
      concentration was observed at 40 min (1.12 (0.05) vs 1.24 (0.04) mmol litre-1; P
      < 0.05) and reached 1.11 (0.05) mmol litre-1 at 60 min (P < 0.01). However, when
      corrected for pH, this decrease was not statistically significant. These results
      suggest that changes in plasma concentrations of sodium rather than changes in
      calcium homeostasis are probably more important in the development of
      transurethral prostatic syndrome.

PMID- 8881641
TI  - Cardiac arrest after Caesarean section under subarachnoid block.
AB  - Cardiac arrest occurred on arrival in the recovery room after emergency Caesarean
      section under subarachnoid block. The patient was resuscitated successfully and
      recovered with no adverse effects. The current literature is reviewed and the
      pathophysiological mechanisms involved in the aetiology of cardiac arrest under
      subarachnoid block are discussed. Early use of adrenaline to treat severe
      bradycardia or hypotension is recommended.

PMID- 8881642
TI  - Severe systemic cholesterol embolization after open heart surgery.
AB  - Cholesterol crystal embolization (CCE) may be triggered by various factors: intra
      arterial angiographic procedures, aortic or vascular surgery, anticoagulant or
      thrombolytic treatments, or both. There are few previous reports of patients
      undergoing coronary artery bypass grafting (CABG) experiencing and therefore
      displaying severe systemic CCE. We describe four patients presenting, shortly
      after CABG, cutaneous, renal, neurological and hepatic signs related to severe
      CCE confirmed by skin biopsy. All patients died 11-92 days after surgery. As
      systemic CCE reveals severe atheromatous disease and is associated with a poor
      prognosis, it is advisable to avoid CABG in patients who present symptoms of CCE
      before surgery.

PMID- 8881643
TI  - CSF progesterone and spread of subarachnoid anaesthesia in pregnancy.

PMID- 8881644
TI  - Sevoflurane.

PMID- 8881645
TI  - Removal of extradural catheters.

PMID- 8881646
TI  - Optimal intracuff pressures with the laryngeal mask.

PMID- 8881647
TI  - Prevention of cardiovascular response to tracheal intubation.

PMID- 8881648
TI  - Analgesia: dose-effect or pre-emptive effect?

PMID- 8881649
TI  - Convective warming after CABG.

PMID- 8881650
TI  - Adequate general anaesthesia--what are we trying to achieve?

PMID- 8881651
TI  - Spinal anaesthesia for Caesarean section.

PMID- 8881652
TI  - Spinal anaesthesia for Caesarean section.

PMID- 8881653
TI  - [The 40th Congress of the Japan Rheumatism Association. Fukushima, Japan. May 23
      25, 1996. Abstracts].

PMID- 8881654
TI  - World Congress on In Vitro Biology. 1996 meeting of the Society for In Vitro
      Biology. San Francisco, California, June 22-27, 1996. Abstracts.

PMID- 8881655
TI  - [71st annual meeting of the Japanese Society of Tuberculosis. Tokyo, March 21-22,
      1996. Abstracts].

PMID- 8881656
TI  - COL3A1 mutations cause variable clinical phenotypes including acrogeria and
      vascular rupture.
AB  - We have recently analysed by histological, protein and molecular DNA techniques
      23 mutations of the collagen III gene (COL3A1), most of which cause premature
      arterial fragility, thin skin and variants of vascular Ehlers-Danlos syndrome.
      There were 14 glycine substitutions between residues 637 and 1021, eight exon
      skips between exons 7 and 45 and one small inframe deletion. The glycine
      substitutions produce a gradient of increasingly abnormal clinical phenotypes
      from exons 36 to 49 while the clinical severity of exon skips is much more
      variable. Each mutation is private for the affected family or individual
      concerned having the potential for early prenatal diagnosis and prevention.

PMID- 8881657
TI  - The atopy patch test: an increased rate of reactivity in patients who have an air
      exposed pattern of atopic eczema.
AB  - In a subgroup of patients with atopic eczema (AE), eczematous skin lesions can be
      induced by epicutaneous testing with aeroallergens (the atopy patch test: APT).
      An increased frequency of positive APT has been found in AE patients showing a
      predictive lesional pattern affecting air-exposed skin areas. This study
      investigates the dose-response of the APT in two different patient groups with
      AE. Petrolatum preparations of house dust mite, cat dander and grass pollen
      allergens in four concentrations (500-10,000 protein nitrogen units) were tested
      epicutaneously in 57 patients with AE, who were prospectively divided in two
      groups according to whether their AE pattern was with (group I) or without (group
      II) a predictive distribution. Sixty-nine per cent of patients in group I, and
      39% in group II, had positive APT reactions (P = 0.02). The reactions in group I
      were elicitable with lower allergen concentrations (P = 0.03). A clinically
      recognizable subgroup of patients with AE showed increased cutaneous sensitivity
      to aeroallergens.

PMID- 8881658
TI  - Functional thrombomodulin expression on epithelial skin tumours as a
      differentiation marker for suprabasal keratinocytes.
AB  - In normal human skin,, immunoreactive thrombomodulin (TM) is expressed in a
      strict differentiation related pattern, solely in suprabasal spinous layer
      keratinocytes. To evaluate the potential application of TM as a differentiation
      marker for keratinocyte-derived skin tumours, we have studied
      immunohistopathological, biochemical and functional TM activities in various skin
      tumours. Immunoreactive, full sized and enzymatically active TM was expressed in
      keratinocyte-derived skin tumours (squamous cell carcinoma, seborrhoeic keratosis
      and partly Bowen's disease), as well as normal epidermal keratinocytes and
      endothelial cells. However, no TM was detected in basal cell carcinomas, senile
      keratosis or non-squamous epithelial tumours such as malignant melanoma, naevus
      pigmentosus and Paget's disease. Interestingly, decreased expression was observed
      in verruca vulgaris. These findings suggested that differentiation-dependent TM
      expression was restricted to epithelial skin tumours and undetectable on neural
      crest derived tumours. TM is a differentiation marker for spinous layer
      keratinocytes and is a useful tool in histopathological study of epithelial
      tumours.

PMID- 8881659
TI  - Interleukin-1 but not tumour necrosis factor alpha synergistically upregulates
      the granulocyte-macrophage colony-stimulating factor-induced B7-1 expression of
      murine Langerhans cells.
AB  - Epidermal Langerhans cells (LC) express several co-stimulatory molecules such as
      B7/BB1, which has been implicated as one of the important determinants for potent
      antigen-presenting function of LC. Recent studies have shown that B7/BB1 antigens
      comprise three distinct molecules termed B7-1, B7-2 and B7-3. Previous studies
      have revealed that the phenotypic and functional properties of murine LC are
      enormously affected by various cytokines including granulocyte-macrophage colony
      stimulating factor (GM-CSF), interleukin-1 (IL-1), and tumour necrosis factor
      alpha (TNF-alpha) derived from surrounding keratinocytes. We have already
      demonstrated that the expression of B7-1 of murine LC is significantly enhanced
      by GM-CSF, IL-1 or TNF-alpha. In this paper, we present that IL-1, but not TNF
      alpha, synergistically up-regulates the GM-CSF-induced B7-1 expression of murine
      LC.

PMID- 8881660
TI  - Selective calmodulin antagonists fail to inhibit phorbol ester-induced superoxide
      anion release from human neutrophils: effects of antifungal azole derivatives.
AB  - The ability of antifungal azole derivatives to inhibit superoxide anion release
      from human leucocytes and the relevance of their documented calmodulin (CaM)
      antagonism was investigated with respect to anti-inflammatory drug activity.
      Econazole, miconazole and clotrimazole were found to inhibit phorbol ester
      induced release of superoxide anions from human polymorphonuclear leucocytes
      effectively with IC50 values in the range of 36-162 mumol/l. In contrast,
      bifonazole and ketoconazole produced minimal or no inhibition, thus suggesting
      that mechanisms other than inhibition of superoxide anion release may largely
      account for their clinical activity in inflammatory skin disorders. The selective
      CaM antagonist J-8, which was used as a reference, failed to inhibit the release
      process, whereas W-7 as a dual CaM/protein kinase C inhibitor induced dose
      dependent inhibition. When tested on protein kinase C activity in vitro,
      econazole, miconazole and clotrimazole were inhibitory, but bifonazole and
      ketoconazole were without significant effect. It is thus concluded that
      inhibition of superoxide anion release reflects the ability of these drugs to
      inhibit protein kinase C, but not their potency to antagonize CaM. Given the role
      of reactive oxygen species in tissue damage by neutrophils, we propose protein
      kinase C, rather than CaM, as another potential target of anti-inflammatory
      therapy.

PMID- 8881661
TI  - Ultrastructural abnormalities in the dermal papillae of both lesional and
      clinically normal follicles from alopecia areata scalps.
AB  - Alopecia areata is a form of balding whose aetiology is uncertain. Although the
      dermal papilla in the hair bulb regulates the follicle and may play a part in the
      pathogenesis of alopecia areata, its ultrastructure has not been well described.
      As clinically normal, i.e. non-balding, follicles from alopecia areata scalps
      show abnormalities at the light microscope level, it would be expected that they
      should exhibit the earliest pathological changes involved in the dysfunction of
      the follicle. This study was designed to investigate the ultrastructure of normal
      human scalp follicular dermal papillae and to see if changes occurred in the
      ultrastructure of dermal papillae from either lesional or non-balding regions of
      alopecia areata. Normal dermal papillae contained well formed fibroblast-like
      cells with large, oval nuclei and well-developed endoplasmic reticulum; the cells
      were separated from each other by extracellular matrix containing small pieces of
      collagen and basal lamina-like material. Dermal papillae from both clinically
      normal and lesional alopecia areata follicles were less well organized and the
      dermal papilla cells exhibited signs of cell injury and contained abnormal
      amounts of pigment; an increased concentration of fibrous material in the
      extracellular matrix and thickening of the dermal papilla-epithelial junction
      were also seen. Follicles from lesional areas showed more pronounced changes than
      clinically normal ones. Ultrastructural abnormalities in the dermal papillae of
      clinically normal scalp follicles support the study of these follicles as a prime
      research target. The changes detected suggest that dermal papilla cells in
      alopecia areata would be less able to synthesize regulatory factors and that
      these may have more difficulty crossing into the epithelial compartment. They are
      consistent with an early pathological role for the dermal papilla in alopecia
      areata, but do not distinguish whether this is a primary aetiological role or a
      secondary response to an insult elsewhere in the follicle.

PMID- 8881662
TI  - In vivo depletion of CD8+ T cells restores hair growth in the DEBR model for
      alopecia areata.
AB  - Alopecia areata (AA) is a putative autoimmune disease in which anagen hair
      follicles are the target of immune cell attack. While both CD4+ and CD8+ T
      lymphocytes are prominent in the infiltrate, their respective roles in the
      pathogenesis of AA remain unknown. Here we directly investigated the activity of
      CD8+ cells in the inhibition of hair growth using the Dundee experimental bald
      rat (DEBR) model for AA. Eight lesional DEBRs were fully depleted of their CD8+
      cells by intraperitoneal injection of OX-8 monoclonal antibody (MoAb) specific
      for these cells over a 15-day therapy course. A control group of eight lesional
      rats was injected with the irrelevant MoAb OX-21. Sequential blood samples were
      analysed by flow cytometry to observe changes in the CD8+ cell population and
      macrophotography used to record changes in hair growth activity. All eight CD8+
      depleted rats started to regrow hair within 29 days from the start of treatment,
      the final response ranging from sparse regrowth to a near normal coat. While two
      rats maintained their new pelage, the remainder lost hair as the CD8+ population
      in peripheral blood increased. Two of the control rats also showed hair regrowth
      over the experimental period of 156 days. These results suggest that CD8+ cells
      play an active part in the pathogenesis of AA. As hair production did not fully
      recover in all animals, immune mechanisms other than CD8+ cells may be involved
      in effecting hair loss. However, analysis of CD8+ cell levels in the skin of CD8+
      depleted rats may help resolve their full importance in AA.

PMID- 8881663
TI  - Assessment of dermal water by high-frequency ultrasound: comparative studies with
      nuclear magnetic resonance.
AB  - Although a principal constituent of human skin, cutaneous water is difficult to
      study, and little is known about water behaviour in physiological and
      pathological conditions of the skin. It has been proposed recently that changes
      in dermal echogenicity measured by high-frequency ultrasonography reflect changes
      in dermal water content. To validate skin ultrasonography for assessment of
      dermal water changes we have studied the relationship between dermal echogenicity
      and skin water content determined by nuclear magnetic resonance technique. Twenty
      MHz ultrasound scanning of the dorsal and ventral forearm skin was performed in
      59 healthy volunteers (age 18-65) and dermal echogenicity was determined by
      counting low echogenic pixels (LEPs) in skin images. 1H magnetic resonance
      spectra were obtained from the same regions and the ratio of areas under the
      water- and fat-specific peaks (W/F) were calculated to measure a relative water
      content. Acute dermal oedema (histamine weal) was studied in the same way in 40
      individuals. Baseline dermal echogenicity correlated significantly with W/F, both
      in the ventral (r = 0.47) and dorsal (r = 0.57) forearm. Intradermal application
      of histamine caused a development of intradermal oedema which could be visualized
      by nuclear magnetic resonance imaging. In a corresponding ultrasound image oedema
      was seen as a low-echogenic area. The proportional increases in LEPs and W/F
      after histamine application were correlated, but the elevation in LEPs was 25-48%
      (95% confidence intervals) higher than that for W/F. These results suggest that
      high-frequency ultrasonography is a sensitive method for assessment of changes in
      dermal hydration. This technique may find important applications in comparative
      and non-invasive evaluations of dermal water in physiological conditions and in
      skin pathologies associated with oedema formation.

PMID- 8881664
TI  - Corticosteroid usage and binding to arginine: determinants of corticosteroid
      hypersensitivity.
AB  - Hypersensitivity to topical corticosteroids is a common cause of allergic contact
      dermatitis. The development of contact allergy is dependent on individual
      susceptibility, exposure to the potential allergen and the ability to penetrate
      the epidermis and react with epidermal protein. We looked at corticosteroid
      binding to arginine and relative usage of corticosteroids to see if these
      variables explain the number of allergic reactions seen to these structurally
      similar chemicals. A linear relationship was found between a measure of
      corticosteroid binding to arginine, the log of relative corticosteroid usage and
      the log of the relative number of corticosteroid allergies. Using multiple
      regression this association was significant (P = 0.01). Statistically, these two
      variables accounted for 73% of the variation in the results. Our results showed
      that the number of corticosteroid allergic reactions was dependent on usage and
      the intrinsic ability of the corticosteroid to degrade and bind to arginine.
      While total corticosteroid usage is unlikely to change, the prescription of
      individual corticosteroids with a reduced potential to degrade and bind to
      protein, but with equal efficacy, might reduce the overall prevalence of
      corticosteroid hypersensitivity.

PMID- 8881665
TI  - Detection of Mycobacterium tuberculosis complex DNA by the polymerase chain
      reaction for rapid diagnosis of cutaneous tuberculosis.
AB  - We assessed the polymerase chain reaction (PCR) technique to detect Mycobacterium
      tuberculosis complex DNA in 48 paraffin-embedded specimens from 32 patients with
      different variants of cutaneous tuberculosis, and compared the results with those
      of culture. A 123 bp product of the IS6110 insertion sequence specific of M.
      tuberculosis complex was amplified and confirmed by digestion with SalI
      restriction endonuclease. The time required for the procedure was 3 days. Thirty
      seven samples (77.1%) were positive for M. tuberculosis complex DNA. No false
      positive results were obtained in nine negative controls. Of the 20 specimens
      tested by PCR and culture, the frequency of positivity was 90% for DNA
      amplification and 65% for culture. In seven cases of lupus vulgaris, the figures
      were 100% and 57%, respectively. In the 11 specimens culture negative or not
      microbiologically tested and PCR negative, evidence for tuberculous infection was
      provided by the correlation of various relative and absolute criteria. These
      results show that PCR amplification of the IS6110 insertion fragment is a rapid
      and accurate means for the detection of M. tuberculosis complex DNA in paraffin
      embedded skin biopsies from patients with cutaneous tuberculosis, especially in
      paucibacillary lesions.

PMID- 8881666
TI  - Topical vitamin D3 (tacalcitol) for steroid-resistant prurigo.
AB  - A topical vitamin D3 ointment (tacalcitol) was prescribed for patients with long
      lasting pruriginous lesions (four with prurigo nodularis and seven with subacute
      prurigo, four of whom had atopic dermatitis). Seven of 11 cases had not responded
      to a topical steroid ointment and even to occlusive application of the ointment.
      Nine of 11 cases showed a significant clinical response to this new regimen
      within 4 weeks. Epidermal Fc epsilon R1(+) dendritic cells were increased in
      number in prurigo nodularis and reduced to normal level after the therapy.
      Topical vitamin D3 ointment might be an alternative therapy for steroid-resistant
      prurigo.

PMID- 8881667
TI  - Expression of intercellular adhesion molecule-1 in UVA-irradiated human skin
      cells in vitro and in vivo.
AB  - Ultraviolet A (UVA) radiation represents an important oxidative stress to human
      skin and certain forms of oxidative stress have been shown to modulate
      intercellular adhesion molecule-1 (ICAM-1) expression. ICAM-1 has been shown to
      play an important part in many immune reactions and the perturbations of this
      molecule by ultraviolet radiation could have implications in many inflammatory
      responses. An enhancement immunohistochemical method with avidin/biotin was used
      for analysing the early effects of UVA radiation on human cell cultures and human
      skin (340-400 nm). Both in vitro and in vivo data show that ICAM-1 staining in
      epidermal keratinocytes, which was expressed constitutively, decreased in a UVA
      dose-dependent manner. The decrease was most noted at 3-6 h following UVA
      radiation with some ICAM-1 staining returning by 48 h post-UVA. ICAM-1 positive
      staining in the dermis was specific for vascular structures and was increased 24
      h after UVA radiation. Cultured dermal fibroblasts exhibited ICAM-1 staining
      which increased slightly within 6-48 h post-UVA radiation. As epidermal ICAM-1
      expression is depleted following UVA radiation and dermal expression increases
      due to an increase in the vascular structures, ICAM-1 provides a valuable marker
      following UVA radiation in human skin that can be readily measured in situ.

PMID- 8881668
TI  - 8-MOP PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen
      with a skin-type approach.
AB  - Two ultraviolet A (UVA) regimens for oral 8-methoxypsoralen (8-MOP)
      photochemotherapy (PUVA) for moderate/severe chronic plaque psoriasis using a
      half body study technique were compared. Each patient received both regimens. A
      higher-dose regimen based on minimal phototoxic dose (MPD) with percentage
      incremental increases was given to one-half of the body. The other half received
      a lower dose regimen based on skin type with fixed incremental UVA increases.
      Patients were treated twice weekly. Symmetrical plaques were scored to determine
      the rate of resolution with each regimen. In addition, the number of treatments,
      cumulative UVA dose and number of days in treatment to achieve overall clearance
      were recorded. Patients were reviewed monthly for 1 year to record remission
      data. Thirty-three patients completed the study. Both regimens were effective and
      well tolerated. With the MPD-based approach, the number of exposures was
      significantly less for patients with skin types I and II but not III. Although
      the cumulative UVA dose was higher with the MPD regimen for all skin types
      studied, the reduced number of exposures required for clearance for skin types I
      and II but not III, combined with the security of individualized MPD testing, has
      practical attractions. MPD testing also identified five patients who required an
      increased psoralen dose and six patients who required a reduction of the initial
      UVA dose with the skin type regimen. Forty-two percent were still clear 1 year
      after treatment and there was no significant difference in the number of days in
      remission between the regimens for those whose psoriasis had recurred. The
      reduction in the number of exposures required for clearance with the MPD-based
      regimen may be safer and more cost effective in the long term.

PMID- 8881669
TI  - Chronic sun exposure alters both the content and distribution of dermal
      glycosaminoglycans.
AB  - Chronic sun exposure leads to structural and functional alterations in exposed
      skin. Photoageing is a process distinct from the changes taking place due to
      chronological ageing. Unique alterations in the dermal extracellular matrix occur
      as a result of photoageing and are responsible for many of these physiological
      changes taking place in sun-damaged skin. Accompanying the deposition of abnormal
      elastic tissue, or solar elastosis, are significant alterations in dermal
      glycosaminoglycans (GAGs). Accumulation of GAGs as a result of photoageing, as
      demonstrated in both humans and animal models of photoageing, seems almost
      paradoxical in view of the large amounts of GAGs present in the skin of newborns,
      making their skin well hydrated and supple, in sharp contrast to the weathered
      appearance of photoaged skin. We investigate the relative GAG content of
      photoaged skin using immunoperoxidase stains specific for hyaluronic acid and
      chondroitin sulphate, and determine the location of these GAGs using confocal
      laser scanning microscopy. Our results demonstrate significant increases in GAG
      staining in sun-damaged vs. sun-protected skin from the same individuals, as
      measured by computer-based image analysis. Furthermore, confocal laser scanning
      microscopy reveals that the increased dermal GAGs in sun-damaged skin are
      deposited on the elastotic material of the superficial dermis of photodamaged
      skin, and not between collagen and elastic fibres as in normal skin. The abnormal
      location of GAGs on these fibres may explain the apparent paradoxical weathered
      appearance of photodamaged skin despite increased GAGs.

PMID- 8881670
TI  - Melanin content and distribution in the surface corneocyte with skin phototypes.
AB  - An individual's sensitivity to sunlight is traditionally assessed by the Boston
      or Fitzpatrick classification of skin type. The ability to tan depends, to some
      degree, on the melanin content of the epidermis. In the study reported here,
      surface corneocytes in exposed skin and unexposed skin have been assessed using a
      surface stripping slide mounting technique and an Optomax V image analyser, with
      which the percentage of corneocyte area occupied by melanin granules has been
      taken as the melanin content index (MCI). There was a significantly different MCI
      between different skin types for both exposed (P < 0.0001) and unexposed (P <
      0.0001) areas using the Kruskal-Wallis one-way ANOVA test. There was also a
      positive significant correlation between MCI and skin types II-VI in both exposed
      (r = 0.95, P < 0.001) and unexposed areas (r = 0.89, P < 0.005). Image analysis
      also demonstrated that the number of melanin granules in surface corneocytes was
      significantly higher in the exposed area compared with the unexposed area, for
      skin types II, III, IV, V and VI. Melanin cap-like structures were also observed
      in exposed corneocytes and heavily pigmented skin contained larger melanin
      particles than fairer skin. The results indicate that an individual's skin
      phototype and melanin content, assessed by image analysis, have a significant
      correlation.

PMID- 8881671
TI  - The use of targeted and non-targeted advertising to enrich skin cancer screening
      samples.
AB  - The purpose of this study was to determine whether the risk factor profile of
      persons attending skin cancer screening clinics could be enriched by appropriate
      advertising prior to the screening events. Eleven screening clinics were held in
      eight rural and three suburban communities. Matched communities were randomly
      assigned to either a target or non-target condition. Targeted communities
      received an advertisement designed to attract high-risk individuals. The
      advertisement listed a number of risk factors and encouraged readers with one or
      more of the listed risk factors to attend the screening. Non-targeted communities
      received a general advertisement requesting individuals who felt they were at
      risk of skin cancer to attend the clinic. Risk factor profiles of all
      participants were measured on the factors listed in the targeted advertisement.
      The risk factor profiles of screenees and the referral rates for skin lesions
      requiring attention were significantly higher in the targeted communities than in
      the non-targeted communities. Lesions suspicious of malignant melanoma or
      Hutchinson's melanotic freckle also were higher, but not statistically
      significant, in the targeted communities. Population samples attending community
      based skin cancer screening clinics can be enriched by appropriate targeted
      advertising prior to the screening events. This has important implications for
      determining the potential cost-effectiveness of population screening programmes.

PMID- 8881672
TI  - Multiple linear lichen planus in the lines of Blaschko.
AB  - The lines of Blaschko describe a distribution pattern which may represent
      embryological development pathways. The distribution may occasionally be followed
      by some skin disorders. We report a patient who had multiple lesions of linear
      lichen planus which followed Blaschko's lines. There were multiple streaks
      affecting several different areas of the body.

PMID- 8881673
TI  - Linear atrophoderma of Moulin: a disease which follows Blaschko's lines.
AB  - Linear atrophoderma of Moulin is a distinctive disease pattern characterized by
      hyperpigmented atrophoderma and described originally in 1992. It follows the
      lines of Blaschko, and occurs without preceding inflammation, subsequent
      induration or scleroderma. The lesions usually develop during childhood or
      adolescence, and the prognosis is good. The differential diagnoses include linear
      dermatoses, e.g. linear scleroderma, epidermal naevi, inflammatory linear
      verrucous epidermal naevus, lichen striatus, Blaschkitis acuta, reticulate
      hyperpigmentation of Iijima and linear lupus erythematosus. Diagnosis is made
      clinically and histologically. We report a 22-year-old woman with a 17 year
      history of linear atrophoderma which involved the right arm and trunk.

PMID- 8881674
TI  - Widespread angiokeratomas and tuberous sclerosis.
AB  - We report a 29-year-old woman who had prominent cutaneous markers of tuberous
      sclerosis, with subependymal nodules and renal cysts on computerized tomographic
      scan, who also showed multiple angiokeratomas widely distributed on the buttocks
      and posterior thighs. Enzymatic studies ruled out Fabry's disease and other
      lysosomal storage disorders. This is the first reported association of widespread
      angiokeratomas and tuberous sclerosis.

PMID- 8881675
TI  - Acquired immunobullous disease: a cutaneous manifestation of IgM
      macroglobulinaemia.
AB  - Waldenstrom's macroglobulinaemia has been associated with a variety of cutaneous
      manifestations. We report a patient with an acquired bullous disorder associated
      with skin fragility and IgM kappa paraprotein. Immunofluorescence studies
      demonstrated bright linear deposition of IgM along the basement membrane zone
      (BMZ), around dermal blood vessels and on arrector pili muscles. Weak
      keratinocyte cell surface staining with IgM was also noted. There was no
      deposition of complement or other immunoglobulins. Indirect immunofluorescent
      studies revealed a circulating IgM anti-BMZ antibody (titre 1/200), which bound
      to both the roof and the floor of a 1 mol/l NaCl split skin substrate.
      Immunoblotting analysis of the patient's serum, with both epidermal and dermal
      extracts, was negative. Treatment with a combination of prednisolone and
      azathioprine was successful. We suggest that this IgM kappa paraprotein has a low
      affinity for an undefined epitope within the lamina lucida, which has produced a
      subepidermal bullous disorder associated with skin fragility.

PMID- 8881676
TI  - Examination of cutaneous macroglobulinosis by immunoelectron microscopy.
AB  - Cutaneous macroglobulinosis is a rare cutaneous manifestation of Waldenstrom's
      disease. Lesions are though to result from accumulation of macroglobulin in the
      dermis and are therefore called IgM storage papules. Ultrastructural findings in
      the previously reported cases were contradictory and the nature of the deposits
      was not established by electron microscopy. The purpose of this study was to
      analyse such deposits by the use of immunoelectron microscopy. A 60-year-old
      woman had multiple erythematous papules for 1 year. The histopathological changes
      consisted of plasmocytic infiltration of the dermis and eosinophilic deposits.
      The skin changes and other investigations led to a diagnosis of Waldenstrom's
      disease. Samples from normal and diseased skin were analysed by electron
      microscopy and by immunogold labelling with anti-IgM antibodies, after Lowicryl
      K4M embedding. An extracellular electron dense granular and filamentous material
      was observed in the mid- and upper dermis, between and within the collagen
      bundles. No periodicity was noted and no deposits were seen at the dermoepidermal
      junction. Immunoelectron microscopy showed a positive labelling located only on
      these deposits, in both normal-appearing skin and in lesions. In this patient,
      immunoelectron microscopy clearly demonstrated the presence of large amounts of
      IgM in the dermis, which were found in the lesions of cutaneous macroglobulinosis
      and in normal skin. These results suggest that the IgM storage papules result
      from a greater density of deposits rather than a site-specific accumulation.

PMID- 8881677
TI  - Skin grafts as pharmacological agents: pre-wounding of the donor site.
AB  - Initially thought to act as tissue replacement, cultured epithelial allografts
      are now known to work by providing a potent stimulus for healing. In a similar
      fashion, we believe that traditional autografts may also provide a stimulus to
      help heal chronic wounds, thus acting as pharmacological agents for healing. We
      attempted to assess the possibility of augmenting the stimulatory properties of
      donor skin by initiating the healing process in the donor region prior to
      grafting. This was accomplished by pre-wounding the donor area 3 days prior to
      harvesting the donor skin. We compared these 'pre-wounded' grafts to those
      harvested immediately. Two patients underwent punch grafting for chronic leg
      ulceration. Half of the ulcer was grafted with donor skin harvested from an area
      that was pre-wounded and the other half from freshly harvested skin. We evaluated
      each for improvement of granulation tissue and degree of edge effect (migration
      of the previously dormant wound edges). All the grafts did well. There was marked
      improvement in granulation tissue in the ulcer bed after grafting, and the
      obvious presence of an edge effect. The edge effect was increased on the site
      where the pre-wounded grafts were placed. It may be possible to augment the
      growth stimulatory properties of donor skin. This may offer therapeutic options
      in patients with chronic wounds.

PMID- 8881678
TI  - The cytotoxic effect of neonatal lupus erythematosus and maternal sera on
      keratinocyte cultures is complement-dependent and can be augmented by ultraviolet
      irradiation.
AB  - To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the
      pathogenesis of the skin lesions in neonatal lupus erythematosus (NLE),
      keratinocytes were cultured, as the target cells, from a patient with NLE and
      from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic
      Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a
      much greater extent than that on normal keratinocytes. A dose of 200 mJ/cm2 UVB
      irradiation on NLE keratinocytes induced a 2.5-3-fold increase in Ro/SSA and
      La/SSB expression compared to non-irradiated cells. Sera derived from both the
      NLE patient and from his mother exhibited a cytotoxic effect on NLE
      keratinocytes, but not on control cells, in the presence of complement.
      Furthermore, the cytotoxicity of the sera was enhanced on UVB-irradiated NLE
      keratinocytes, whereas it had no cytotoxic effects on UVB-irradiated control
      cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on
      the surface membrane of NLE keratinocytes induces the autoantibodies and
      complements to injure the cells. This complement-mediated cytotoxic effect can be
      augmented by UV irradiation, a concept not incompatible with the exacerbation of
      the skin eruption in sun-exposed skin sites.

PMID- 8881680
TI  - Recombinant granulocyte colony-stimulating factor in the management of toxic
      epidermal necrolysis.
AB  - We report a 7-year-old girl with extensive toxic epidermal necrolysis (TEN) and
      neutropenia who was successfully treated using recombinant granulocyte colony
      stimulating factor. Our patient had extensive epidermal loss and neutropenia,
      both indicators of a poor prognosis, but none the less made a rapid and complete
      recovery.

PMID- 8881679
TI  - Digital calcification in systemic sclerosis: effective treatment with good tissue
      preservation using the carbon dioxide laser.
AB  - Tissue calcification of the fingers associated with limited systemic sclerosis is
      a common problem and is the source of considerable morbidity as it may be
      extremely tender and cause considerable functional disability. The current
      treatment of digital calcification is unsatisfactory. We evaluated the use of the
      carbon dioxide (CO2) laser in the management of this condition in six patients
      with the limited form of systemic sclerosis. A total of 21 areas of symptomatic
      digital calcification of the fingers were treated. Complete resolution of
      symptoms occurred in 12, moderate response with partial improvement was seen in
      five, little improvement was observed in two, and recurrence of calcinosis was
      found in two. The patient's average healing time was 6 weeks (range 4-10). The
      median duration of follow-up was 20 months (range 12-40). Postoperative infection
      was seen in two patients, and resolved completely in both with the use of topical
      and oral antibiotics. We found the CO2 laser a simple and effective treatment for
      most of the symptomatic lesions of digital calcification, and it may obviate the
      need for deforming surgery in many cases.

PMID- 8881681
TI  - Allopurinol: a therapeutic alternative for disseminated cutaneous sarcoidosis.
AB  - We report a 57-year-old woman, with progressive disseminated cutaneous
      sarcoidosis, whose eruption responded to treatment with allopurinol.

PMID- 8881682
TI  - Delayed hypersensitivity reactions to corticosteroids applied to mucous
      membranes.
AB  - Despite the widespread use of corticosteroids on the mucous membranes of the
      nose, eye and bronchial tree, mucosal contact sensitivity has apparently been
      uncommon. However, since the introduction of new corticosteroids such as
      tixocortol pivalate and budesonide, mucosal contact sensitivity, particularly
      that affecting the nasal mucosa, has increasingly been reported. Contact allergy
      on other mucosal surfaces and in the bronchial tree is very rare. We report three
      women who had contact allergy to tixocortol pivalate or budesonide in nasal
      sprays, and one woman who had an allergic contact stomatitis from tixocortol
      pivalate in oral lozenges.

PMID- 8881683
TI  - Minocycline-induced discolouration of the sclerae.
AB  - We report two patients with minocycline-induced pigmentation of the sclerae.
      Cutaneous pigmentation is a well-recognized complication of minocycline therapy,
      but only five cases of pigmentation of the sclerae have been described
      previously. These five patients have a number of features in common with the two
      reported here. We propose that these patients represent the most severe end of
      the spectrum of minocycline-induced cutaneous changes. Patients should be warned
      about the possibility of the occurrence of pigmentary changes before starting
      therapy.

PMID- 8881684
TI  - Minocycline-induced pigmentation resolves after treatment with the Q-switched
      ruby laser.
AB  - Four patients with minocycline-induced cutaneous pigmentation were treated with
      the Q-switched ruby laser. The pigmentation resolved and there was no adverse
      effects.

PMID- 8881685
TI  - An eruption associated with alphavirus infection.
AB  - Some alphaviruses, e.g. Sindbis, cause an acute febrile illness associated with
      papular rashes and arthralgia. The diagnosis is usually serological and, hence,
      the histopathology of the rashes has been poorly elucidated. We report on two
      patients with rapidly healing eruptions associated with Sindbis virus infection.
      The histopathology of the rashes showed large, pronounced lymphohistiocytic
      infiltrates with atypical lymphoid cells around the hair follicles, changes not
      usually seen in rapidly-healing dermatoses.

PMID- 8881686
TI  - Mycobacterium kansasii infection limited to the skin in a patient with AIDS.
AB  - We describe a case of cutaneous Mycobacterium kansasii infection in a 56-year-old
      man with acquired immunodeficiency syndrome, who received treatment with
      trimethoprim-sulphamethoxazole for Pneumocystis carinii pneumonia. Resolution of
      the cutaneous lesion was observed without specific treatment.

PMID- 8881687
TI  - Salivary gland lymphoplasmacytoid lymphoma with nodular cutaneous amyloid
      deposition and lambda chain paraproteinaemia.
AB  - We report the case of an 83-year-old woman who developed a lymphoplasmacytoid
      lymphoma of the salivary glands with extension to the skin of the cheeks and
      laterocervical area. The most remarkable feature was the massive amyloid
      deposition that gave the cutaneous lesions a distinctive clinical appearance,
      similar to that observed in cases of nodular cutaneous amyloidosis. An IgM-lambda
      paraprotein was also detected in the serum.

PMID- 8881688
TI  - Treatment of nodular prurigo with cyclosporin (treat the disease, not just the
      symptoms)

PMID- 8881689
TI  - Cutaneous vasculitis.

PMID- 8881690
TI  - Narrow-band UVB phototherapy for severe atopic dermatitis.

PMID- 8881691
TI  - Protein contact dermatitis.

PMID- 8881692
TI  - Polypoid melanoma is not rare.

PMID- 8881693
TI  - Celery soup causing severe phototoxicity during PUVA therapy.

PMID- 8881694
TI  - Bullous pemphigoid localized to the mouth.

PMID- 8881695
TI  - Modulation of serum eosinophil cationic protein levels by cyclosporin in severe
      atopic dermatitis.

PMID- 8881696
TI  - Alpha interferon-induced hair discolouration.

PMID- 8881697
TI  - Semecarpus anacardium-induced facial oedema.

PMID- 8881699
TI  - Onycholysis in sarcoidosis--a previously undescribed association.

PMID- 8881698
TI  - Hyper-IgE multicentric Castleman's disease: eosinophilic skin eruption,
      generalized lymphadenopathy, and polyclonal hyperimmunoglobulinaemia with an
      extremely high serum IgE level.

PMID- 8881700
TI  - Nutritional deficiency and the skin in Shwachman syndrome.

PMID- 8881701
TI  - Squamous cell carcinoma of the scalp following a chemical burn and chronic
      discoid lupus erythematosus.

PMID- 8881702
TI  - Intimate associations between PGP9.5-positive nerve fibres and Langerhans cells.

PMID- 8881703
TI  - Perniosis--a possible association with a preleukaemic state.

PMID- 8881704
TI  - [The 38th Annual Meeting of the Japanese Society of Child Neurology. July 18-20,
      1996. Tokyo, Japan. Abstracts].

PMID- 8881705
TI  - [The 31st Conference of Japanese Medical Society of Alcohol and Drug Studies.
      September 13-14, 1996. Yokohama, Japan].

PMID- 8881706
TI  - Multi-frequency bioelectric impedance measurements for predicting body water
      compartments in patients with non-ascitic liver cirrhosis.
AB  - We assessed total body water (TBW) and extracellular water (ECW) in thirty-four
      non-ascitic cirrhotics and twenty healthy controls by 2H2O and Br dilution. In
      the same subjects, bioelectric impedance (BI) was recorded at multiple
      frequencies. Body hydration was similar for controls (mean 55.6 (SD 6.7)), less
      severe cirrhotics (Child-Pugh classification A; CPA; n 21, mean 56.2 (SD 6.2))
      and moderately-severe cirrhotics (Child-Pugh classification B; CPB; n 13, mean
      57.2 (SD 5.4)). However, intracellular water standardized per litre TBW was
      significantly higher in CPB subjects (mean 27.0 (SD 7.5); P < 0.01) compared with
      CPA (mean 21.3 (SD 10.6)) and control subjects (mean 18.0 (SD 9.8)). Published
      formulas for predicting TBW and ECW from BI at multiple frequencies were applied
      to the cirrhotics. These formulas gave accurate predictions of TBW and ECW,
      although standard errors of estimates were higher for CPB subjects (TBW < or =
      2.5 and ECW < or = 2.1 l) than those for CPA (TBW < or = 2.0 and ECW < or = 1.8
      l) and control (TBW 1.4 and ECW 0.9 l) subjects.

PMID- 8881707
TI  - Iron nutrition and anaemia in a malaria-endemic environment: haematological
      investigation of the Gidra-speaking population in lowland Papua New Guinea.
AB  - Blood examination was conducted for the four Gidra-speaking village groups in
      Papua New Guinea, who were characterized by high Fe intake and high malaria
      prevalence with marked inter-village differences. The northern riverine
      villagers, whose Fe intake was higher than the other three village groups, did
      not suffer from Fe-deficiency anaemia in their malaria-endemic environment; nor
      did the inland villagers, with their second highest Fe intake and their malaria
      free environment, suffer from Fe-deficiency anaemia. However, several individuals
      of the southern riverine village suffered from anaemia in a malaria-endemic
      environment, although their Fe intake was almost the same as the inland
      villagers'. A considerable proportion of the coastal villagers were anaemic,
      reflecting the lowest Fe intake and the highest malaria prevalence. An inter
      village comparison of the relationships between haemoglobin levels and
      transferrin saturation revealed that the southern riverine villagers needed
      smaller amounts of circulating Fe for erythropoiesis than the northern riverine
      and inland villagers, reflecting the long-term human-environment conditions such
      as the density of malaria vectors and the people's dietary habits. Fe
      supplementation was not judged effective against hypoferraemia and/or anaemia in
      such a population. As the incidence of malaria had no significant long-lasting
      effect on Fe stores or circulating Fe concentration, but did have an effect on
      anaemia, the hypothesis that malaria causes a transfer of Fe from the blood to
      parenchymal tissues as a defence against infectious diseases was not supported.

PMID- 8881708
TI  - The influence of ammonia, biogenic amines and gamma-aminobutyric acid on grass
      silage intake in sheep.
AB  - We investigated whether biogenic amines alone, or a combination of NH3, amines
      and gamma-aminobutyric acid (GABA) influenced grass-silage intake, intake
      behaviour and rumen liquid content in sheep. Three diets were studied: a grass
      silage preserved with formic acid (4 litres/tonne) (FAS), FAS with 4.9 g
      amines/kg DM added (FAS+A), and FAS supplemented with a combination of N
      components at the following concentrations: 2.7 g amines, 3.0 g NH3 and 5.0 g
      GABA/kg DM (FAS+C). The diets were offered ad libitum, once daily to six rumen
      cannulated Texel wethers in a crossover design. Daily DM intake (DMI; g DM/d)
      tended to be influenced by diet (P = 0.08). The DMI of FAS+A was similar to that
      of FAS alone, whereas that of FAS+C tended to be higher. The mean rate of
      ingestion (g DM/min) over all feeding bouts tended to be the lowest for FAS+A (P
      = 0.06). No differences were found among the diets concerning intake behaviour
      during the principal meal. Average intake rate of the small meals tended to be
      the lowest for FAS+A (P = 0.06). Although rumen NH3 concentration was higher (P <
      0.05) after the principal meal, rumen pH, osmolality, rumen pool size and liquid
      content were not significantly altered by adding amines or the mixture of N
      components to FAS. We conclude that biogenic amines or N-containing products of
      protein fermentation in concentrations normally found in poor-quality silages do
      not reduce the intake of well-preserved formic acid-treated silage. A direct
      effect on chemostatic regulation of intake was not observed, but a slight
      negative effect on silage palatability cannot be excluded.

PMID- 8881709
TI  - The effect of condensed tannins from heated and unheated cottonseed on the ileal
      digestibility of amino acids for the growing rat and pig.
AB  - The effect of condensed tannins (CT) from heated and unheated cottonseed on the
      apparent ileal digestibility of amino acids for the growing rat and pig was
      determined. In Expt 1, twenty-four rats were allocated to four semi-purified
      diets which contained cottonseed kernel and hulls as the only protein source. Two
      of the diets contained unheated solvent-extracted cottonseed kernel and hulls,
      while the remaining two diets contained similar material but which had been heat
      treated by autoclaving at 110 degrees for 120 min. In Expt 2, twelve rats and
      twelve pigs were fed on four semi-purified diets containing commercial cottonseed
      meal (CSM) as the only protein source. Cr2O3 was added to all diets as an
      indigestible marker. For each pair of diets in both experiments, PEG was either
      included or excluded. The effect of CT was assessed by comparing control animals
      (-PEG; CT acting) with PEG-supplemented animals (+PEG; CT inactivated). Ileal
      contents from the terminal 150 and 450 mm of ileum were collected at slaughter, 7
      h from the start of feeding, for the rats and pigs respectively. Apparent ileal
      amino acid digestibility for rats fed on the diet containing cottonseed kernel
      and hulls was significantly depressed by the heat treatment, particularly for
      lysine and threonine. On average, apparent ileal amino acid digestibility in the
      diets without PEG was decreased from 0.80 to 0.70 by heat treatment. Dietary
      cottonseed CT depressed apparent ileal protein digestibility in the pig and in
      the rat. The addition of PEG to the diets significantly increased the apparent
      ileal digestibility of N and some amino acids for the pigs and the rats. The mean
      increase in apparent ileal digestibility due to PEG addition for the fourteen
      amino acids was 2 percentage units in both species fed on the commercial CSM
      diets, and 2 or 4 percentage units in rats fed on the unheated or the heated
      cottonseed kernel and hull diets respectively. The effect of PEG was similar in
      the heated and unheated cottonseed kernel and hulls for most amino acids, but
      apparent ileal digestibilities of threonine, tyrosine and lysine were increased
      more by PEG in heated than in unheated CSM. Apparent ileal N digestibility was
      lower in the pig than in the rat. For several of the amino acids there were
      significant animal species differences in apparent ileal digestibility. Studies
      into the effects of cottonseed CT should be carried out in the target animal
      species. The commercial CSM had a low apparent ileal amino acid digestibility
      overall, particularly for the essential amino acids lysine and threonine. It was
      concluded that effects of heating did not eliminate the reversible reactivity of
      cottonseed CT on amino acid digestion in rats and pigs but rather appeared to
      increase it for threonine, tyrosine and lysine in Expt 1, causing large
      reductions in apparent ileal digestibility of these amino acids.

PMID- 8881710
TI  - Utilization of endogenous and dietary urea in the large intestine of the mature
      horse.
AB  - The dynamics of N metabolism in mature horses were investigated when they were
      fed on a low-N diet or the same diet supplemented with sufficient urea or soybean
      meal to meet their theoretical N requirements. There were no differences in DM,
      organic matter or neutral-detergent-fibre digestibilities for the three diets. N
      digestibilities and digestible-N intakes were similar for the urea- and soyabean
      supplemented diets and very low for the low-N diet. For all three diets plasma
      urea was degraded in the digestive tract to NH3 which was utilized by the
      bacterial population as a N source. NH3 was absorbed from the large intestine
      into the blood and converted to urea. NH3 was also incorporated into plasma
      proteins. The horses fed on the low-N diet degraded a greater proportion of
      endogenous urea in the digestive tract than did horses fed on the urea-or
      soyabean-supplemented diets. However, the horses fed on the urea diet had the
      highest degradation rate of urea. The quantity of urea degraded in the digestive
      tract of horses fed on the urea-supplemented and the low-N diets could not
      compensate for a lack of dietary crude protein in these diets. The horses were in
      a negative N balance when fed on the low-N and urea-supplemented diets and a
      positive N balance when fed on the soyabean-supplemented diet. Dietary urea
      supplementation did not benefit the horses.

PMID- 8881711
TI  - Hypolipidaemic, gastrointestinal and related responses of broiler chickens to
      chitosans of different viscosity.
AB  - Broiler chickens (1-d-old) were fed ad libitum on a control diet based on maize
      and maize starch or diets containing low-, medium- or high-viscosity chitosans at
      an inclusion level of 15 g/kg. Body weights and feed intakes of chickens given
      chitosan-containing diets were generally depressed in comparison with those of
      control-fed animals on days 11 and 18 of the experiment. On days 12 and 19,
      feeding the low-viscosity-chitosan diet reduced plasma triacylglycerol and total
      plasma cholesterol concentrations in relation to chickens receiving the control
      diet, while the medium- and high-viscosity-chitosan-containing diets reduced
      total plasma cholesterol and elevated, although not significantly, plasma HDL
      cholesterol concentrations compared with those of control-fed animals. Chitosan
      feeding generally improved plasma HDL-cholesterol:total cholesterol ratio in
      comparison with control feeding, which was attributed to the general reductions
      in plasma cholesterol concentrations rather than increases in plasma HDL
      cholesterol concentrations. Feeding the high-viscosity-chitosan-containing diet
      significantly reduced the ileal digestibility of crude protein (N x 6.25) and
      crude fat compared with chickens given the control diet. The reduction in ileal
      crude fat digestibility was greatest among chickens receiving the high-viscosity
      chitosan-containing diet and chitosan-containing diets reduced ileal fat
      digestibility by 8% on average compared with that of control-fed birds. However,
      increasing the viscosity of the chitosan fraction could not be correlated with
      increases in terminal ileal digesta viscosity and, therefore, it could not be
      established that increased ileal lumen viscosity alone contributed to reductions
      in body weight, feed intake and plasma cholesterol concentrations. However, the
      fact that ileal digestibility of fat was reduced by feeding chitosan to chickens
      suggests the action of other hypolipidaemic mechanisms.

PMID- 8881712
TI  - Changes in the concentration of fructose in the blood of piglets of different
      ages after doses of fructose, fructose plus glucose, and sucrose.
AB  - We investigated the hydrolysis of sucrose in the small intestine and the
      subsequent absorption and metabolism of fructose in sucking piglets by measuring
      temporal changes in the concentration of fructose in the plasma following the
      administration of physiological amounts of these carbohydrates. Calculations of
      the area under the curve for fructose in the plasma showed that there was no age
      limit to the piglets' ability to absorb fructose. However, there was a limit to
      the amount of fructose that the younger piglets could get from a dose of sucrose.
      Indeed, we demonstrated that there was a positive linear correlation between a
      piglet's capacity to hydrolyse sucrose and the age of the piglet up to 15 d of
      age (r 0.98). The half-life for fructose was 495, 103, 38, 49 and 28 min in 2-, 5
      , 7-, 10- and 15-d-old piglets respectively and, thus, there was only limited
      utilization of fructose in the younger piglets. However, there were 13.0- and 1.4
      fold increases in the elimination rate of fructose from the plasma of piglets
      from 2 to 7 d and from 7 to 15 d respectively, consistent with the reported
      increase in the deposition of fat in piglets of a similar age range. Hence, the
      effective metabolism of fructose may be partially dependent on the amount of
      adipose tissue present and the phosphorylation of this monosaccharide by
      hexokinase (EC 2.7.1.1) in this tissue.

PMID- 8881714
TI  - Mammary sensitivity to protein restriction and re-alimentation.
AB  - The present study tested the influence of protein undernutrition and re
      alimentation on mammary gland size and secretory cell activity in lactating rats.
      During gestation, female Sprague-Dawley rats were offered a high-protein diet
      (215 g crude protein (N x 6.25; CP)/kg DM; H); litters were standardized to
      twelve pups at parturition. During lactation, two diets were offered ad libitum,
      diet H and a low-protein diet (90 g CP/kg DM; L). Lactational dietary treatments
      were the supply ad libitum of either diet H (HHH) or diet L (LLL) for the first
      12 d of lactation, or diet L transferring to diet H on either day 6 (LHH) or 9
      (LLH) of lactation. On days 1, 6, 9 and 12 of lactation, rats from each group (n
      > or = 6) were used to estimate mammary dry mass, fat, protein, DNA and RNA; the
      activities of lactose synthetase (EC 2.4.1.22) enzyme and Na+,K(+)-ATPase (EC
      3.6.1.37) were also measured. Rats offered a diet considered protein sufficient
      (H) from day 1 of lactation showed a decrease in mammary dry mass and fat but an
      increase in DNA, RNA and protein on day 6, after which there was no further
      change, except for mammary protein which continued to increase. However, rats
      offered diet L showed a steady loss in mammary mass and fat throughout the 12 d
      lactation period and no change in mammary DNA, RNA or protein. Rats previously
      protein restricted for either the first 6 or 9 d of lactation had their mammary
      dry mass and mammary fat loss halted and showed a rapid increase in mammary DNA,
      RNA and protein on re-alimentation. Lactose production in group HHH, as measured
      by lactose synthetase activity, was similar on days 1 and 6 of lactation, after
      which a significant increase was seen. Protein-restricted rats showed no change
      in lactose synthetase activity during the 12 d experimental period. Changing from
      diet L to diet H led to a significant increase in lactose synthetase activity to
      levels comparable with those offered diet H from day 1. These results show that
      rats offered a protein-restricted diet during lactation suffer mammary
      underdevelopment, but this may be rapidly reversed by re-alimentation with a high
      protein diet.

PMID- 8881713
TI  - Maintenance of villus height and crypt depth, and enhancement of disaccharide
      digestion and monosaccharide absorption, in piglets fed on cows' whole milk after
      weaning.
AB  - The aims of the present study were (a) to maintain the structure and function of
      the small intestine of the piglet after weaning, and (b) to compare the capacity
      in vivo of sucking and weaned piglets to digest oral boluses of lactose and
      sucrose and absorb their monosaccharide products. Piglets were fed on cows' whole
      milk ad libitum every 2 h for 5 d after weaning. Physiological doses of lactose
      plus fructose (treatment LAC+FRU) and sucrose plus galactose (treatment SUC+GAL)
      were administered on day 27 of lactation and on the fifth day after weaning,
      after which time piglets were killed. Villus height and crypt depth were
      maintained (P > 0.05) by feeding cows' milk after weaning. The areas under the
      curves (AUC) for galactose and glucose, adjusted for live weight and plasma
      volume, increased (P < 0.05) after weaning. Despite the enhancement of gut
      function after weaning, the galactose index (GalI:AUC for galactose ingested as
      lactose divided by the AUC for the same dose of galactose ingested as the
      monosaccharide) and fructose index (FruI: AUC for fructose ingested as sucrose
      divided by the AUC for the same dose of fructose ingested as the monosaccharide),
      which are indices of digestive and absorptive efficiency, both decreased after
      weaning. This apparent anomaly may be reconciled by increased growth, and hence
      surface area, of the small intestine between weaning and slaughter such that
      'total' digestion and absorption most probably increased despite apparent
      decreases in GalI and FruI. Positive correlations (P < 0.05) between villus
      height and GalI are consistent with the maximum activity of lactase occurring
      more apically along the villus. Significant linear relationships (P < 0.05) were
      recorded between villus height at the proximal jejunum and adjusted AUC for
      galactose and glucose following treatment LAC+FRU, and between villus height at
      the proximal jejunum and adjusted glucose AUC following treatment SUC+GAL. These
      relationships suggest that maximum digestion and absorption occurs at increasing
      distances along the crypt:villus axis in the weaned pig.

PMID- 8881715
TI  - Modification of the fatty acid composition of dietary oils and fats on
      incorporation into chylomicrons and chylomicron remnants.
AB  - Possible changes in the fatty acid composition of dietary fats and oils which
      might occur during digestion, absorption and formation of chylomicrons and
      chylomicron remnants were investigated. Chylomicrons were collected from the
      thoracic duct of rats tube-fed with olive, maize, palm or fish oil or butter fat,
      and their fatty acid composition was determined and compared with that of their
      parent lipids. In turn, these lipoproteins were converted to chylomicron remnants
      in functionally hepatectomized rats and their composition re-determined. The
      predominant fatty acids in each of the oils and fats also predominated in their
      respective chylomicrons, but their proportions were reduced during the processes
      leading to their formation. Endogenous contributions of linoleic,
      eicosapentaenoic, and docosahexaenoic acids were particularly noted when these
      fatty acids were not well-represented in the original oils and fats, suggesting
      that they may be obligatory constituents in the formation of chylomicrons. The
      conversion of chylomicrons to remnants further attenuated the extremes in fatty
      acid composition of the dietary oils and fats. These results indicate that
      following an acute intake of oil or fat, the resulting chylomicrons and
      chylomicron remnants presented to the tissues contain a more balanced
      distribution of saturated, mono- and polyunsaturated fatty acids than the oils
      and fats from which they were derived.

PMID- 8881716
TI  - The relationships between dietary alpha-linolenic:linoleic acid and rat platelet
      eicosapentaenoic and arachidonic acids.
AB  - Increased dietary intake of alpha-linolenic acid (ALA) may be desirable to enrich
      tissue eicosapentaenoic acid (EPA; 20:5n-3) but competition between n-3 and n-6
      fatty acids for enzymes involved in elongation and subsequent acylation will
      determine the relative proportions of phospholipid fatty acids. The aim of the
      present study was to examine the effects of altering the dietary ALA:linoleic
      acid (LA) ratio on rat platelet EPA and arachidonic acid (AA; 20:4n-6)
      concentrations. Sprague-Dawley rats were fed on diets containing 30% total energy
      as fat with approximately 10% each of saturated, monounsaturated and
      polyunsaturated fatty acids with one of the following ALA:LA values; 1:7, 1:4,
      1:1 or 1.3:1 (nine rats per group). After 4 weeks, blood was withdrawn from the
      abdominal aorta and platelet fatty acids analysed. The proportion of EPA was
      greater at the 1:1 and 1.3:1 ratios compared with the 1:7 and 1:4 (P < 0.05), and
      a decrease in AA was observed (P < 0.05) at the higher ratios. It was established
      that the platelet EPA:AA value increased (P < 0.05) as the dietary ALA:LA value
      increased.

PMID- 8881717
TI  - Flavin metabolism during respiratory infection in mice.
AB  - Previous control studies carried out in children showed that respiratory
      infection alters riboflavin metabolism and leads to excessive urinary losses of
      the vitamin. In order to understand the nature of biochemical changes in
      riboflavin metabolism during respiratory infection, a study was carried out using
      the mouse as the experimental model, and Klebsiella pneumoniae as the infective
      organism. Mice were fed on either a low (0.5 mg/kg)- or high (13.3 mg/kg)
      riboflavin semi-synthetic diet. Infection resulted in a 5-6-fold higher excretion
      of riboflavin in the urine of mice fed on the low-riboflavin diet. Higher
      erythrocyte FAD levels and lower liver FAD levels were also observed during
      infection. Of the four enzymes involved in the synthesis and breakdown of the
      flavin coenzymes studied, the activity of hepatic flavokinase (ATP: riboflavin 5'
      phosphotransferase; EC 2.7.1.26) was significantly lower, and that of FAD
      synthetase (ATP: FMN adenylyltransferase; EC 2.7.7.2) was higher during
      riboflavin restriction and infection. The activity of FMN (acid) phosphatase (EC
      3.1.3.2) was unchanged, whereas FAD (nucleotide) pyrophosphatase (EC 3.6.1.9)
      activity was significantly higher both with the low-riboflavin diet and during
      infection. Thyroid hormone is known to modulate flavokinase activity and, hence,
      thyroid status was assessed. Plasma triiodothyronine (T3) levels were not
      affected, but thyroxine levels were lower in the mice fed on the low-riboflavin
      diet. However, plasma T3 was significantly lower during infection, suggesting a
      mechanistic role for the hormone in the reduction of flavokinase activity.

PMID- 8881718
TI  - Effect of dietary calcium intake and meal calcium content on calcium absorption
      in the rat.
AB  - Fifty-four male and forty-five female 7-week-old rats, Wistar strain, average
      weights 190 g and 140 g respectively, were randomized by weight into three groups
      of eighteen rats each (males) and three groups of fifteen rats each (females) and
      fed on a semi-purified diet containing (per kg) 2 (low), 5 (normal) or 20 g
      (high) Ca as CaCO3 for 2 weeks. Each group was then further randomized into three
      groups of six rats each (males) and five rats each (females) and given a meal (10
      g of the same diet) containing either 2, 5 or 20 g Ca as 47CaCO3. 47Ca was
      determined in quantitative daily collections of faeces over 7 d and fractional
      absorption of 47Ca estimated by extrapolating the linear portion (days 3-7) of
      the plot of log 47Ca retention v. time back to the time of isotope
      administration. Absorption of meal Ca was higher in males than in females and was
      affected similarly in males and females by previous dietary Ca intake and meal Ca
      content. Fractional absorption of meal Ca decreased with increasing previous
      dietary Ca intake and with increasing meal Ca content, and the combined effect of
      these two variables caused fractional Ca absorption to vary from 11-89%. Absolute
      absorption of meal Ca decreased with increasing previous dietary Ca intake and
      increased with increasing meal Ca content. The influence on Ca absorption of
      variations in meal Ca content (load effect) was greater than that of variations
      in previous dietary Ca intake (adaptive effect). These results show that previous
      dietary Ca intake and meal Ca content are both major determinants of Ca
      absorption from meals in intact rats fed in the normal way and that the rat
      responds to these factors in a manner similar to that reported for humans. This
      study provides further evidence of similarities between rats and humans in
      dietary Ca absorption.

PMID- 8881719
TI  - American Society for Gastrointestinal Endoscopy annual meeting. San Francisco,
      California, May 19-22, 1996. Abstracts.

PMID- 8881720
TI  - American Society of Andrology, 21st annual meeting. Minneapolis, Minnesota, April
      25-29, 1996. Abstracts.

PMID- 8881721
TI  - What is clinical audit?
AB  - The emphasis of clinical audit should be on improvement in care. Audit can only
      improve healthcare if it includes a mechanism for change. The fact that
      information about outcomes is collected does not necessarily mean that care is
      being audited, nor that improved care will result. Audit must be distinguished
      from data collection, surgical epidemiology, and research.

PMID- 8881722
TI  - Aneurysms of the visceral and renal arteries.
AB  - Visceral aneurysms represent a rare clinical entity; however, 10-20% will rupture
      and this is accompanied by a significant mortality rate of 20-70%, depending on
      the location of the aneurysm. The incidence, pathogenesis and clinical aspects of
      splanchnic and renal artery aneurysms are reviewed from the available literature
      and the problems of diagnosis and treatment are discussed. Their incidence is
      increasing and controversy still exists regarding their treatment. The decision
      for intervention has to take into account the size and the natural history of the
      lesion, the risk of rupture, which is high during pregnancy, and the relative
      risk of surgical or radiological intervention. For most asymptomatic aneurysms,
      expectant treatment is acceptable. For large, symptomatic or aneurysms with a
      high risk of rupture, surgery is advisable. An alternative treatment is the use
      of endovascular techniques, ie embolisation, or graft stent insertion.

PMID- 8881723
TI  - Myocardial perfusion scintigraphy in patients undergoing major non-vascular
      abdominal surgery.
AB  - The prognostic value of myocardial perfusion scintigraphy is beginning to be
      recognised in patients undergoing cardiovascular surgery. The aim of this
      prospective study was to assess the predictive value of scintigraphy in elderly
      patients undergoing major non-vascular abdominal surgery. Adenosine stress
      thallium-201 (201Tl) single-photon emission tomography (SPET) was employed for
      imaging using a standard protocol. Patients over the age of 60 years (n = 55)
      with an intermediate to high likelihood of coronary artery disease were evaluated
      prospectively. The clinical outcome variables analysed were cardiac mortality and
      major cardiac morbidity occurring within 30 days of surgery. Cardiac events were
      cardiac death (n = 5), angina pectoris (n = 5), nonfatal mycardial infarction (n
      = 1), acute left ventricular failure (n = 2) and arrhythmias requiring treatment
      (n = 4). All cardiac events occurred in the first 10 postoperative days except
      one cardiac death which happened on the 29th postoperative day. Patients with an
      abnormal 201Tl SPET scan had a higher risk of postoperative death (4 vs 1) or any
      postoperative cardiac event (13 patients vs 4 patients; P < 0.0001) when compared
      with those with a normal scan. The sensitivity, specificity and positive
      predictive value of 201Tl imaging for perioperative ischaemia and adverse
      outcomes were 76%, 82% and 65%, respectively. The occurrence of an intraoperative
      event (P < 0.02) and the length of surgery (P < 0.01) were also predictors of a
      postoperative cardiac event. Clinical risk variables and an abnormal
      electrocardiogram in isolation were poor predictors. In conclusion, preoperative
      myocardial perfusion scintigraphy is a valuable technique for identifying elderly
      patients with a high risk for cardiac events when undergoing major non-vascular
      abdominal surgery.

PMID- 8881725
TI  - Fragmentation in the pursuit of quality: the dental dilemma.

PMID- 8881726
TI  - Catheterisation technique: overcoming gel blockage.

PMID- 8881724
TI  - Per[cyst]ent growth: the odontogenic keratocyst 40 years on.

PMID- 8881727
TI  - Day-stay tonsillectomy: is hospital stay reduced at the expense of increased
      community care?
AB  - There is concern about the burden day-stay surgery created upon community
      services. We have followed 128 children and 38 adults undergoing day-stay
      tonsillectomy and a similar cohort of adults and children undergoing
      tonsillectomy as inpatients and looked at the demands made on general practice
      and casualty services over the 2 weeks after discharge. Twelve adults (18%) and
      four children (3%) required overnight admission after day-stay surgery. Within
      the first 2 weeks, 27 adults (48.2%) and 62 children (50%) visited their GP and
      13 adults (23.2%) and six children (4.8%) visited the casualty department. There
      was no statistically significant difference for either adults or children when
      comparing the day-stay and inpatient cohorts. Adult day-stay tonsillectomy is
      associated with a high admission rate. Both adult and paediatric tonsillectomy
      lead to considerable demand for general practice and casualty services, but this
      demand is high regardless of whether the day-stay or inpatient route is chosen.

PMID- 8881728
TI  - Management of epistaxis: a national survey.
AB  - A survey to assess variations in management and outcome of patients admitted with
      epistaxis was conducted. A questionnaire was sent to all consultant
      otolaryngologists working at NHS hospitals in England and Wales requesting
      information about management of patients admitted with epistaxis over a 3 month
      period. Data analysis of information provided by 102 consultants for a total of
      933 patients was performed. The average number of patients admitted with
      epistaxis over a period of 3 months per consultant was 10.2. More than 70% of the
      patients were aged 60 years or over. Approximately 75% of the patients required
      nasal packing; the most common pack used was BIPP (Bismuth Iodine Paraffin
      Paste). Of the patients, 5.6% required general anaesthesia, with less than 1%
      requiring formal arterial ligation. The mean duration of stay in hospital was 2.9
      days. Few complications were reported. Patients admitted with epistaxis were
      generally managed conservatively, with very few requiring surgical intervention.
      There was remarkable consensus in various aspects of management of patients
      admitted with epistaxis.

PMID- 8881729
TI  - Hepatitis B vaccine uptake among surgeons at a London teaching hospital: how well
      are we doing?
AB  - In order to determine the perceptions of surgical staff of the risks of hepatitis
      B virus (HBV) infection and its prevention through vaccination, and to assess
      frequency of 'sharps' injuries and compliance with the Department of Health (DoH)
      recommendations on vaccination, a questionnaire was distributed to surgical staff
      in the Guy's and St Thomas' Hospital Trust. Only 52 of the 88 surgeons who
      responded (59%) had documented vaccine-induced immunity to HBV. Eighty-five (97%)
      had received at least one dose of vaccine but 15 of these (18%) had failed to
      complete the course. Of the 70 surgeons completing the course, only 56 (80%) had
      had their immune responses checked and only 44 (63%) admitted sustaining a
      'sharps' injury at least once a month, yet only 17% consistently reported these
      injuries. Those least likely to report were cardiothoracic and obstetric and
      gynaecology surgeons; these specialties also sustained the highest frequency of
      'sharps' injuries. Ophthalmologists, who sustained the lowest rate of injury,
      were most likely to report. In conclusion, a significant number of surgeons
      appeared not to have completed a course of hepatitis B vaccine in the presence of
      a high frequency of 'sharps' injuries. Following the publication of DoH
      guidelines on protecting workers from HBV, it must be stressed that failure to
      comply with recommendations may have medicolegal implications.

PMID- 8881730
TI  - Impact of MRI on a knee arthroscopy waiting list.
AB  - As part of a waiting list initiative, magnetic resonance imaging (MRI) scans were
      arranged for 69 patients waiting for knee arthroscopy. All patients had a
      clinical diagnosis of a meniscal tear. With 11 non-attenders, 58 scans were
      performed. Of the patients scanned, 35 had demonstrable meniscal tears, and five
      patients had other pathology on their scans. All patients were reviewed
      clinically after their scans, and 24 patients were removed from the waiting list.
      After a further 9 months, only one of the 24 patients removed had been re-listed
      for therapeutic arthroscopy. This initiative proved a cost-effective method of
      reducing waiting times for knee arthroscopy.

PMID- 8881731
TI  - Soft tissue sarcoma of the extremity.
AB  - A retrospective review of 33 cases of soft tissue sarcoma of the extremity
      presenting over a 10 year period was undertaken. The history, patterns of
      referral, diagnostic investigations, procedures undertaken and outcomes were
      studied. We found there was a frequent delay in diagnosis and sometimes
      misinterpretation of biopsy specimens. Patients were seen by a variety of
      specialists from disciplines such as general surgery, plastic surgery,
      orthopaedic surgery and rheumatology. Considerable progress has been made in the
      treatment of soft tissue sarcomas, often allowing local control of the tumour
      without amputation. We believe there should be early referral of patients having
      these tumours to a centre where a combined multidisciplinary approach can be
      undertaken.

PMID- 8881732
TI  - Palliation of malignant dysphagia: an alternative to surgery.
AB  - This paper presents the results of palliative treatment of 474 patients with
      malignant dysphagia. Laser produces good relief of symptoms but requires frequent
      repetition. Self-expanding metal stents provide one-off relief of dysphagia but
      do have complications. A randomised trial of laser versus covered and uncovered
      metal stents has demonstrated improved relief of dysphagia of stents over laser,
      but highlighted the problems at the cardia when stents are used. Chemotherapy in
      patients with advanced adenocarcinoma using epirubicin, cisplatin and 5
      fluorouracil produces a response in two-thirds of cases, with relief of dysphagia
      and possible increase in survival. A treatment plan for palliation of patients
      with malignant dysphagia is presented.

PMID- 8881733
TI  - Video-assisted thoracoscopy in the evaluation of penetrating thoracic trauma.
AB  - The management of patients who present with penetrating thoracic trauma but are
      haemodynamically stable may be subjective and imprecise. We report our initial
      experience with the use of video-assisted thoracoscopy in a series of five
      patients in whom accurate assessment was achieved and unnecessary thoracotomy
      avoided.

PMID- 8881734
TI  - Anxiety in patients with symptomatic breast disease: effects of immediate versus
      delayed communication of results.
AB  - Immediate reporting of fine needle aspiration biopsy (FNAB) specimens has been
      introduced into many breast clinics; in others, women return to a later clinic to
      receive the result. This delay in communication of results may lead to elevated
      anxiety. This study compared anxiety levels in two groups having FNAB. One group
      received results at the initial clinic visit (n = 51), the other having delayed
      communication (n = 51). Anxiety was measured using the six-item short form of the
      Spielberger State-Trait Anxiety Inventory (STAI-SSF) and was administered before
      and after each consultation. Initial anxiety was high in both groups. Women with
      malignant results had higher post-communication anxiety compared with women with
      benign results. However, within the group with benign results (the vast
      majority), immediate communication was associated with a significantly greater
      fall in STAI-SSF scores from before to after the first consultation (U = 587.0; P
      < 0.02). There was no difference between the immediate and delayed communication
      among women with a malignant diagnosis (U = 26.0; P = 0.91). These results
      provide preliminary support for the more widespread introduction of a cytologist
      into breast clinics to allow immediate communication of results.

PMID- 8881735
TI  - Long-term review of coeliac axis compression syndrome.
AB  - Coeliac axis compression syndrome is a rare condition, characterised by chronic
      intermittent colicky upper abdominal pain after eating, associated with weight
      loss and an epigastric bruit. Typically, the patient is an otherwise fit young to
      middle-aged adult. The diagnosis requires the exclusion to other causes of upper
      gastrointestinal pathology, and is suggested by narrowing or occlusion of the
      coeliac axis on angiography. The pathophysiology of this finding and the complex
      of symptoms in a typical patient remains unclear. Carefully selected patients
      seem to derive long-term benefit from decompression.

PMID- 8881736
TI  - Duplex-guided compression of femoral artery false aneurysms reduces the need for
      surgery.
AB  - In a 1-year period, 13 patients underwent duplex-guided compression (DGC) of
      femoral artery false aneurysms. Of the 13 false aneurysms, 11 arose after cardiac
      catheterisation, and DGC was successful in 10 (77%) cases. The number of
      percutaneous cardiological procedures has risen over the past 5 years, and with
      time a greater proportion of these procedures have become more complex, involving
      coronary angioplasty or coronary stenting. The rate of vascular complications has
      risen from 0.2% in 1991-1992 to 0.61% in 1994-1995. Duplex-guided compression has
      reduced the number of operations performed for the vascular complications of
      percutaneous cardiological procedures by 50%. No complications have arisen from
      DGC, and it is recommended as the first line of management for femoral artery
      false aneurysms after percutaneous cardiological procedures.

PMID- 8881737
TI  - A systematic review of the effectiveness and safety of laparoscopic
      cholecystectomy.

PMID- 8881738
TI  - Blood transfusion requirements in femoral neck fractures.

PMID- 8881739
TI  - Minimum standards for the management of cleft lip and palate: efforts to close
      the audit loop.

PMID- 8881740
TI  - Laparoscopic orchidopexy: one-stage alternative for non-palpable testes.

PMID- 8881741
TI  - Iatrogenic accessory nerve injury.

PMID- 8881742
TI  - The treacherous fibroadenoma: a 'mighty mouse'.

PMID- 8881743
TI  - An audit of one surgeon's experience of oral squamous cell carcinoma using a
      computerised malignancy database.

PMID- 8881744
TI  - Cumulative index: volumes 15-24. January 1996.

PMID- 8881745
TI  - The Nramp1 antimicrobial resistance gene segregates independently of resistance
      to virulent Mycobacterium tuberculosis.
AB  - Nramp1 is a recently cloned gene that is involved in resistance of mice to
      infection with certain microbial pathogens, including the attenuated bacillus
      Calmette-Guerin (BCG) strain of Mycobacterium bovis, as well as certain other
      mycobacteria. With a view to determining whether Nramp1 influences resistance of
      mice to infection with virulent M. tuberculosis, BALB/c mice homozygous for the
      susceptibility allele of Nramp1, and DBA/2 mice homozygous for the resistance
      allele, as well as their F1 and F2 progeny, were typed according to their
      possession of these alleles using a 'hot start' polymerase chain reaction (PCR)
      procedure. As assessed by the ability of the mice to survive infection, the
      results show that Nramp1 plays no discernible role in resistance to tuberculosis.

PMID- 8881746
TI  - Analysis of peptide-binding motifs for two disease associated HLA-DR13 alleles
      using an M13 phage display library.
AB  - Major histocompatibility complex (MHC) molecules bind peptides bearing an
      appropriate 'sequence motif' for MHC binding. The use of phage display libraries
      exploits the ability of MHC class II molecules to exchange peptides in solution
      and thus select out peptide sequences with high-affinity binding from a large
      array of random peptides. We have analysed the peptide binding motifs of HLA
      DRB1*1301 and *1302 using affinity purified HLA-DR13 molecules to purify
      sequentially HLA-DR13-binding peptides from a large random library of M13 phage
      containing nonamer inserts in the pIII coat protein. These DR13 alleles differ
      only at position 86 of the HLA-DR beta chain, where they contain valine and
      glycine residues respectively. These alleles were chosen because of their
      association with protection from severe malaria and chronic hepatitis B virus
      infection in West Africa. Analysis of the phage bound to these DR molecules
      suggests binding motifs. We compare the results derived from the use of the phage
      display library with results obtained from analysis of eluted peptides and
      peptide-binding studies. This analysis shows that although there is a common
      theme to motifs derived using different methods, there are also subtle variations
      between them.

PMID- 8881747
TI  - Synthetic peptides non-covalently bound to bacterial hsp 70 elicit peptide
      specific T-cell responses in vivo.
AB  - We have examined the immunogenicity of complexes formed by non-covalent
      association of a synthetic peptide corresponding to influenza A virus
      nucleoprotein, residues 206-229 (pNP) and Mycobacterium tuberculosis heat-shock
      protein 70 (hsp 70). One or two injections of these complexes given to BALB/c
      mice without any additional adjuvant, were capable of eliciting very strong
      peptide-specific proliferative T-cell responses in the spleen. These responses
      were dependent on the stability of the complex since immunogenicity was lost when
      dissociated with ATP prior to immunization. T-cell responses to hsp 70 were
      easily generated by immunization with the purified chaperone alone, either after
      primary or secondary immunization. Injection of pNP-hsp 70 complexes, however,
      although generating good primary responses, resulted in very much decreased
      proliferative responses to the hsp 70.

PMID- 8881748
TI  - Induction of antibody-secreting cells and T-helper and memory cells in murine
      nasal lymphoid tissue.
AB  - Intranasal (i.n.) immunization is an effective route for inducing mucosal immune
      responses especially in the upper respiratory tract and mouth. To characterize
      the cells involved in these responses, nasal lymphoid tissue (NALT; considered to
      be the equivalent of Waldeyer's ring in humans) of normal mice, and of mice
      immunized intranasally with a bacterial protein antigen conjugated to cholera
      toxin B subunit, was isolated and the lymphoid cells analysed according to
      surface phenotype, immunoglobulin and antibody secretion, and cytokine profile.
      Compared with cells obtained from Peyer's patches (PP), NALT cells contained a
      higher proportion of T cells, especially naive (CD45RB+hi) T-helper cells, and
      fewer surface (s)IgA+ cells. Both tissues contained high proportions of sIgM+
      IgD+ unswitched B cells. After i.n. immunization, IgA antibody-secreting cells
      were increased, indicating that isotype switching and differentiation of B cells
      to IgA-secreting cells occurred in NALT, whereas smaller numbers of antibody
      secreting cells were found in PP after intragastric (i.g.) immunization. Antigen
      specific memory cells persisted in NALT for at least 8 months after initial
      immunization. The cytokine expression profiles of antigen-stimulated NALT and PP
      cells of immunized mice, revealed by reverse transcription polymerase chain
      reaction analysis of mRNA, were similar. Both NALT and PP cells tended to express
      type 2 earlier or for longer than type 1 cytokine mRNA, but NALT cells tended to
      express interleukin-4 (IL-4) earlier, and IL-5 for a longer period, than PP
      cells. Thus NALT shares with PP cell populations typical of a mucosal inductive
      site, including unswitched B cells and naive T-helper (Th) cells. After i.n.
      immunization, NALT has the capacity to provide help for B-cell maturation and
      differentiation, as well as to maintain immune memory.

PMID- 8881749
TI  - Expansion of cytotoxic CD8+ CD28- T cells in healthy ageing people, including
      centenarians.
AB  - Ageing is associated with complex remodelling in the phenotypic and functional
      profiles of T lymphocytes. We investigated whether expression of CD28 antigen on
      T cells is conserved throughout adulthood and ageing in humans. For this purpose
      we analysed T cells obtained from peripheral blood of 102 healthy people of ages
      ranging from 20 to 105 years. We found an age-related increase of CD28- T cells
      in percentage and absolute number, predominantly among CD8+ T cells. CD28- T
      cells from aged donors analysed by flow cytometry appeared as resting cells (not
      expressing CD25, CD38, CD69, CD71, DR), bearing markers of cytotoxic activity (CD
      11b and CD 57) and with a phenotype compatible with 'memory' cells (up-regulated
      CD2 and CD11a; CD62L absent). At the functional level, freshly isolated purified
      CD28- CD8+ T cells showed high anti-CD3 redirected cytotoxic activity against Fc
      bearing P815 cells. The same activity tested on freshly isolated bulk T
      lymphocytes was significantly augmented with age. We found a positive correlation
      between age, number of CD8+ CD28- T cells and anti-CD3 redirected cytotoxicity by
      freshly isolated T cells. These data suggest that an activation of unknown nature
      within the cytotoxic arm of the immune system occurs with age. We speculate that
      these cytotoxic T lymphocytes (CTL) in vivo may constitute armed effector cells
      for immediate killing of targets bearing peptides from pathogens of intracellular
      origin.

PMID- 8881750
TI  - Factors that influence activated CD8+ T-cell apoptosis in patients with acute
      herpesvirus infections: loss of costimulatory molecules CD28, CD5 and CD6 but
      relative maintenance of Bax and Bcl-X expression.
AB  - The expanded CD8+ T-lymphocyte population arising in response to viral infection
      controls the virus but could also prove damaging to the host unless safely
      removed at the end of the immune response. Apoptosis provides a mechanism whereby
      this can be achieved, as apoptotic cells are recognized and engulfed by
      macrophages. Peripheral blood CD8+ T lymphocytes from individuals with acute
      viral infections were highly susceptible to apoptosis after short-term culture in
      vitro. This spontaneous cell death could be prevented by interleukin-2 (IL-2) and
      was related to a decreased expression of Bcl-2 but not Bax or Bcl-XL, additional
      molecules that promote or prevent apoptosis, respectively, as well as an increase
      in CD95. After stimulation with anti-CD3 antibody, T cells from these patients
      also underwent an activation-induced cell death (AICD) that could not be
      prevented by IL-2. Interestingly, CD8+ T cells from this patient group expressed
      lower than normal levels of three costimulatory molecules, CD28, CD5 and CD6,
      suggesting that stimulation in the absence of a second signal is a possible
      mechanism for the defective reactivation of these cells. Thus multiple
      mechanisms, including loss of Bcl-2, increased CD95 and loss of costimulatory
      molecules, place constraints on the survival and reactivation of activated CD8+ T
      cells after viral infections. This enables immune activation to be controlled and
      cellular homeostasis to be re-established during resolution of viral diseases in
      vivo.

PMID- 8881751
TI  - Limited heterogeneity of biased T-cell receptor V beta gene usage in lung but not
      blood T cells in active pulmonary sarcoidosis.
AB  - Sarcoidosis is a multisystem disorder characterized by non-caseating granulomas
      and the accumulation of CD4+ T cells in involved tissues such as the lung. To
      evaluate the diversity of the CD4+ T-cell repertoire in this disorder, a detailed
      clonal analysis was performed in five individuals with active sarcoidosis who
      demonstrated preferential accumulation of T cells expressing the T-cell receptor
      variable gene family V beta 8 in either the lung or blood. In three individuals,
      analysis of unselected samples of nucleotide sequences derived from V beta 8+
      lung T cells demonstrated degrees of clonality ranging from 11% to 46%,
      indicating the expansion of limited numbers of V beta 8+ T-cell clones in the
      lung. Analysis of the corresponding deduced amino acid sequences demonstrated
      common VDJ junctional amino acid residues in the dominant V beta 8+ T-cell clones
      derived from two oligoclonal V beta 8+ lung T-cell populations, consistent with
      an antigen-specific T-cell response. In contrast, analysis of V beta 8+ CD4+ T
      cells from the blood of an individual with a marked bias for peripheral blood V
      beta 8+ T cells demonstrated no evidence of oligoclonality, suggesting that the
      stimulus for circulating biased V beta-specific T cells in sarcoidosis may derive
      from a different, perhaps superantigenic, origin. Clinical improvement in the
      disease either in response to treatment with corticosteroids or as a result of
      spontaneous resolution was associated with a decrease in the proportion of V beta
      8-specific T cells in the biased lung and/or blood T-cell compartments. Together,
      these observations are consistent with a role for this T-cell subset in the
      clinical manifestations of active granulomatous disease.

PMID- 8881752
TI  - Structural mutations in the constant region of the T-cell antigen receptor
      (TCR)beta chain and their effect on TCR alpha and beta chain interaction.
AB  - The region responsible for T-cell receptor (TCR)alpha and beta chain assembly has
      previously been shown to reside in their extracellular domains. In an attempt to
      delineate further the structural requirements for TCR alpha and beta chain
      assembly, chimeric TCR beta chains with increasing length of constant (C) region
      and mutant TCR beta chains with C-domain point mutations were constructed. Their
      ability to assemble with wild-type TCR alpha chain was evaluated in non-T (COS
      cells) or T cells. The results reveal that the C beta domain is the binding
      region to TCR alpha chain, whereas the intact variable (V), diversity (D) and
      joining (J) regions with a short C-domain of beta chain are not sufficient for
      the TCR alpha and beta chain assembly. The unique interchain disulphide bond
      between TCR alpha and beta chains is not required for the TCR alpha beta
      heterodimer formation.

PMID- 8881753
TI  - Development of CD8 alpha/beta + TCR alpha beta intestinal intraepithelial
      lymphocytes in athymic nu/nu mice and participation in regional immune responses.
AB  - On the basis of the CD8 coreceptor expression, T-cell receptor (TCR)alpha beta
      bearing intestinal intraepithelial lymphocytes (i-IEL) segregate into two
      populations. The CD8 alpha alpha + TCR alpha beta i-IEL develop thymus
      independently, whereas the CD8 alpha beta + TCR alpha beta i-IEL are generally
      considered to be thymus dependent. Flow cytometry analysis revealed a distinct
      population of CD8 alpha beta + TCR alpha beta i-IEL in individual athymic nu/nu
      mice. The i-IEL encompassing CD8 alpha beta + TCR alpha beta cells expressed
      potent cytolytic and interferon-gamma-producing activities. These findings
      demonstrate that CD8 alpha beta + TCR alpha beta i-IEL can develop in nu/nu mice
      independently from a functional thymus and suggest that these cells, directly or
      indirectly, perform biological functions in the gut.

PMID- 8881754
TI  - Role of the CD6 glycoprotein in antigen-specific and autoreactive responses of
      cloned human T lymphocytes.
AB  - CD6 is a 130 000 MW T-cell surface glycoprotein that can deliver coactivating
      signals to mature T lymphocytes. Studies using monoclonal antibodies (mAb) have
      defined at least four epitopes on CD6, and distinct functional responses are
      elicited by mAb to the different epitopes. The function of CD6 is unknown.
      Multiple CD6 ligands are predicted, based on data that a soluble CD6 fusion
      protein precipitates at least three peptides. A cDNA clone for one of these
      ligands, termed activated leucocyte-cell adhesion molecule (ALCAM) has recently
      been isolated. In order to further characterize the role of CD6 in cell-cell
      interactions, we have examined the role of CD6 in a variety of responses by
      tetanus toxoid (TT) specific human T-cell clones. Anti-CD6 mAb UMCD6 (epitope 3)
      inhibits antigen-specific responses of such clones to TT, but not to the
      superantigen SEA. Responses of clones to nominal antigen are CD6-dependent using
      either peripheral blood mononuclear cells (PBMC) or macrophage-depleted E rosette
      negative cells as the antigen-presenting cell (APC) population. Furthermore,
      these clones made autoreactive with DNA methyltransferase inhibitors express
      increased CD6, and autoreactivity is inhibited by UMCD6. Taken together, the data
      suggests the existence of a functional CD6 ligand in peripheral blood which is
      expressed by APC, including cells other than macrophages. Interactions between
      CD6 and CD6 ligands may regulate both antigen specific and autoreactive responses
      of human T lymphocytes.

PMID- 8881755
TI  - CD4+ cytolytic effectors are inefficient in the clearance of Listeria
      monocytogenes.
AB  - Cytotoxic T lymphocytes (CTL) recognize and lyse target cells through the
      interaction of the T-cell receptor complex with the class I or class II major
      histocompatibility complex (MHC). The production of class I-restricted CTL has
      been shown to be critical to the elimination of specific pathogens including
      Listeria monocytogenes. However, the function of class II-restricted CTL in the
      clearance of intracellular pathogens is poorly understood. H-2b beta 2
      microglobulin-deficient mice (beta 2M-/-) are not able to produce CD8+ CTL in
      response to infection with L. monocytogenes. We used this model to evaluate the
      efficacy of class II-restricted CTL, in the absence of a class I-restricted
      response, during a primary infection with L. monocytogenes. We demonstrate that,
      despite their effectiveness in adoptive transfer of protection, Listeria-specific
      CD4+ class II-restricted cytotoxic lymphocytes are ineffective in decreasing
      titres of L. monocytogenes in the spleen was found established infection. In beta
      2M-/- mice, persistence of L. monocytogenes in the spleen was found
      preferentially in class II-negative cells. Surprisingly, class I-restricted CTL
      from C57BL/6 mice were capable of decreasing bacterial titres during an
      established infection even in the absence of detectable class I on the surface of
      cells from beta 2M-/- mice. These data strongly suggest that, in the absence of a
      class I-restricted response, pathogens that elicit a class II-restricted
      cytotoxic response may escape prompt eradication by the immune system.

PMID- 8881756
TI  - Contribution of extrathymic gamma delta T cells to the expression of heat-shock
      protein and to protective immunity in mice infected with Toxoplasma gondii.
AB  - We demonstrated that gamma delta T cells contribute to protective immunity
      against Toxoplasma gondii by inducing the expression of a 65,000 MW heat-shock
      protein (hsp 65) in host macrophages. Here we examined the role of extrathymic
      and intrathymic gamma delta T cells in protective immunity and hsp 65 expression
      in mice infected with T. gondii. Intrathymic gamma delta T cells were obtained
      from severe combined immunodeficiency (SCID) mice grafted with syngeneic fetal
      thymus (TG-SCID), in which only T cells derived from the donor thymus developed,
      whereas extrathymic gamma delta T cells were obtained from nude mice that lack
      thymus. Extrathymic gamma delta T cells from T. gondii-infected nude mice
      differed from intrathymic gamma delta T cells of infected TG-SCID mice, in terms
      of Thy1.2 expression and V-region gene usage of T-cell receptor (TCR) gamma
      delta. Extrathymic gamma delta T cells expressed extremely high levels of Thy1.2,
      and had V gamma 7 repertoire but lacked V gamma 5,6 and V delta 1,5. On the other
      hand, intrathymic gamma delta T cells express intermediate and low levels of
      Thy1,2. These cells possessed V gamma 5,6 and V delta 1,5 but failed to rearrange
      the V gamma 7 gene. Peritoneal macrophages from infected nude mice contained hsp
      65, whereas this protein was scarcely expressed in those of infected TG-SCID
      mice. Transfer of extrathymic, but not of intrathymic gamma delta T cells to SCID
      mice enabled their macrophages to express hsp 65. Athymic nude mice were
      significantly resistant to the infection compared with SCID mice which lack gamma
      delta T as well as alpha beta T cells. The resistance was dependent upon
      extrathymic gamma delta T cells, since nude mice depleted of gamma delta T cells
      using a corresponding monoclonal antibody became extremely susceptible. These
      results indicated that extrathymic rather than intrathymic gamma delta T cells
      play some crucial roles in protection against T. gondii and in hsp 65 expression.

PMID- 8881757
TI  - Afferent lymph veiled cells stimulate proliferative responses in allogeneic CD4+
      and CD8+ T cells but not gamma delta TCR+ T cells.
AB  - Dendritic cells were identified in afferent lymph derived by lymphatic
      cannulation of cattle, stained with monoclonal antibody (mAb) to the bovine
      workshop cluster 6 (WC6) antigen, which is highly expressed on bovine afferent
      lymph veiled cells, and sorted with a fluorescence-activated cell sorter. These
      cells expressed major histocompatibility complex (MHC) class I and II and CD1b
      but not CD14. They bound human and murine CTLA4-immunoglobulin (CTLA4-Ig) fusion
      proteins indicating expression of CD80 and or CD86. Dendritic cells induced
      proliferative responses in allogeneic CD4+ and CD8+ cells sorted from blood but
      did not induce responses in purified allogeneic WC1+, gamma/delta T cells, which
      are CD2-, CD4-, CD8- and are the major gamma delta T-cell population in cattle
      blood, even when interleukin-2 (IL-2) was added to cultures. A WC1-, CD2+ gamma
      delta T-cell receptor (TCR)+ population predominates in cattle spleens and
      proliferation of a T-cell line with this phenotype was not induced by allogeneic
      dendritic cells, with or without added IL-2. The observations imply that the
      ligand for the gamma delta TCR expressed on the two populations is not present on
      allogeneic dendritic cells or that the costimulatory molecules expressed on
      dendritic cells that render them highly effective at stimulating MHC class I- and
      class II-restricted CD8+ and CD4+ T cells are not recognized by the WC1+ or WC1-
      gamma/delta T cells. Expression of CD28 by the four cell types was assessed by
      reverse transcriptase-polymerase chain reaction (RT-PCR). Purified CD4+ and CD8+
      cells both produced CD28 transcripts but neither purified WC1+ cells nor the WC1-
      gamma delta TCR+ cell line did so. The findings indicate that CD80 and or CD86
      are involved in the stimulation of CD4+ and CD8+ alpha beta TCR+ T cells but not
      in the stimulation of either of the two gamma delta TCR+ populations.

PMID- 8881758
TI  - Induction of intercellular adhesion molecule-1 in human nasal epithelial cells
      during respiratory syncytial virus infection.
AB  - The effects of infection with respiratory syncytial virus (RSV) on expression of
      intercellular adhesion molecule (ICAM)-1 was determined in vitro in nasal
      epithelial cell cultures. Functional consequences of changes in ICAM-1 expression
      were assessed by measuring adhesion of a human leukaemic T-cell line to RSV
      infected epithelial cells. Also, adhesion of phytohaemagglutinin-activated
      tonsillar lymphocytes (TL) to RSV-infected epithelial cells caused a significant
      increase in interleukin (IL)-4 or IL-5 production. Release of these cytokines was
      adhesion dependent as non-adherent TL produced significantly less IL-4 or IL-5.
      However, no significant difference was observed for IL-2 or interferon-gamma (IFN
      gamma) production. These observations suggest that RSV-infected epithelial cells
      may induce T-helper type-2 (Th2)-like cytokines by mucosal lymphocytes during
      mucosal infection in vivo.

PMID- 8881760
TI  - Preparation of monoclonal anti-porcine CD3 antibodies and preliminary
      characterization of porcine T lymphocytes.
AB  - The CD3-T-cell receptor complex is the clonotypic surface structure by which T
      lymphocytes recognize foreign antigens and are subsequently activated. Because of
      the low immunogenicity of the CD3 molecules, anti-CD3 monoclonal antibodies (mAb)
      are difficult to prepare and have not been available in several species.
      Following isolation of porcine CD3, 14 anti-porcine CD3 mAb were prepared, which
      define six groups of CD3-epsilon epitopes, coprecipitate two types of TCR and
      reveal considerable heterogeneity of CD3 expression amongst lymphocyte
      subpopulations. Thus, both CD3 positive and negative subpopulations of CD2 or CD8
      positive cells were found in the blood. The density of CD3 on CD2+ or CD8+ cells
      was relatively low and heterogeneous, whereas the CD2-, CD8- or MAC320+ T cells
      expressed CD3 at a higher and more homogeneous level. Finally, in the thymus,
      staining with anti-CD3 resolved large thymocytes into two subsets: one expressing
      a high level of CD3 and the other being negative. In contrast, small thymocytes
      expressed CD3 at a low and more homogeneous level. Immunohistological studies
      confirmed the presence of clearly detectable CD3 in thymus medulla and the T-cell
      regions of peripheral lymphoid tissues. Most of the mAb were mitogenic, when
      presented to peripheral blood mononuclear cells in immobilized form. The anti-CD3
      mAb also induced redirected cytotoxicity which was shown to be Fc receptor
      dependent.

PMID- 8881759
TI  - Treatment of established adjuvant arthritis in rats with monoclonal antibody to
      CD18 and very late activation antigen-4 integrins suppresses neutrophil and T
      lymphocyte migration to the joints and improves clinical disease.
AB  - The migration of leucocytes from blood into the joint is a key feature of human
      and experimental arthritis. Adhesion molecules on leucocytes and vascular
      endothelium are important in this process and may be therapeutic targets for
      intervention in arthritis. We investigated whether monoclonal antibody treatment
      to block the alpha 4 integrin, very late activation antigen-4 (VLA-4), and beta 2
      integrins (CD11/CD18) administered to rats during the preclinical (day 5) or
      clinical phase (day 10+) would modify disease. When treatment was initiated 5
      days after induction of disease, development of arthritis was significantly
      reduced by either anti-alpha 4 (TA-2) or anti-beta 2 (WT.3) monoclonal antibodies
      (mAb) and the combination of both mAb was even more effective (clinical scores:
      control 11.4; anti-alpha 4 6.6; anti-beta 2 6.8; anti-alpha 4 + anti-beta 2 3.9).
      When treatment was delayed until arthritis was apparent (day 10), the anti-alpha
      4 + anti-beta 2 mAb combination still significantly diminished the arthritis
      score on day 14 (control 13; anti-alpha 4 + anti-beta 2 7.9). Treatment with anti
      alpha 4 + anti-beta 2 mAb decreased the migration to the joints of blood
      polymorphonuclear leucocytes (PMNL) by 66-79% and of spleen T lymphocytes by 56
      75%, depending on the joint. In contrast, PMNL migration was abolished (> 98%)
      and T-cell migration markedly (87%) inhibited to dermal inflammatory reactions in
      the same animals. These findings demonstrate: that blocking mAb to alpha 4 and
      beta 2 integrins can reduce the severity of adjuvant arthritis, even after joint
      inflammation has developed; that this treatment can markedly inhibit PMNL and T
      lymphocyte migration to the joints; and that yet to be defined mechanisms
      distinct from alpha 4 (CD49d) and beta 2 (CD11/CD18) integrins, also contribute
      to leucocyte migration to inflamed joints. Identifying these additional adhesion
      mechanisms may be required to control joint inflammation further.

PMID- 8881761
TI  - Activation by mitogens and superantigens of axolotl lymphocytes: functional
      characterization and ontogenic study.
AB  - Urodele amphibians have weak and slow immune responses compared to mammals and
      anuran amphibians. Using new culture conditions, we tested the ability of
      lymphocytes of a well-studied salamander, the Mexican axolotl (Ambystoma
      mexicanum) to proliferate in vitro with diverse mitogenic agents. We demonstrated
      that the axolotl has a population of B lymphocytes that proliferate specifically
      and with a high stimulation index to the lipopolysaccharide (LPS) known as a B
      cell mitogen in mammals. This proliferative capacity is observed without
      significant changes throughout ontogenesis. In the presence of LPS, axolotl B
      lymphocytes are able to synthesize and secrete both isotopes of immunoglobulin
      described in this species, IgM and IgY. Moreover, a distinct lymphocyte
      subpopulation is able to poliferate significantly in response to the mitogens
      usually known as T-cell specific in mammals, phytohaemagglutinin (PHA) and
      concanavalin A (Con A). The activated cells are T lymphocytes, as shown by
      depletion experiments performed in vitro with monoclonal antibodies, and in vivo
      by thymectomy. Splenic T lymphocytes of young axolotls (before 10 months) do not
      have this functional ability, which suggests maturation and/or migration
      phenomena during T-cell ontogenesis in this species. Axolotl lymphocytes are able
      to proliferate in vitro with a significant stimulation index to staphylococcal
      enterotoxins A and B (SEA and SEB). These products act on mammalian lymphocytes
      as superantigens: in combination with products of the major histocompatibility
      complex (MHC), they bind T-cell receptors with particular V beta elements. The
      fact that these superantigens are able to activate lymphocytes of a primitive
      vertebrate suggests a striking conservation of molecular structures implied in
      superantigen presentation and recognition.

PMID- 8881762
TI  - Signal transduction through mu kappa B-cell receptors expressed on pre-B cells is
      different from that through B-cell receptors on mature B cells.
AB  - We introduced kappa light chain genes into pre-B cells to increase the surface mu
      HC expression, and established transfectants expressing mature type of B-cell
      receptors (BCR) on pre-B-cell surfaces. Since the cytoplasmic conformations of
      the reconstituted BCR and intrinsic pre-B-cell receptor (pre-BCR) are identical,
      they would be connected with the identical signal transduction pathways in pre-B
      cells. By using the transfectants, we revealed that the reconstituted BCR on pre
      B cells was functionally equivalent to BCR on mature B cells in terms of the
      induction of intracellular Ca++ mobilization. However, we found that the signal
      transduction pathways through BCR on pre-B cells were quantitatively different
      from those mature B cells in two ways. First, cross-linkage of the reconstituted
      BCR on pre-B cells induced preferential tyrosine phosphorylation of p120 and
      p100, which was not observed when BCR on mature B cells was cross-linked. Second,
      BCR in pre-B cells was physically associated with a larger amount of
      phosphatidylinositol-3 kinase (PI-3K) than BCR in mature B cells in spite of the
      fact that both pre-B and B cells expressed a similar amount of PI-3K in
      cytoplasm. Signals through pre-BCR and BCR are known to cause distinct biological
      effects in B-cell development. The biochemical features in the downstream of
      reconstituted BCR on pre-B cells, which we revealed in this study, will be of
      help in understanding the mechanism of functional differences between pre-BCR and
      BCR.

PMID- 8881763
TI  - Chemotaxis of human B lymphocytes to anti-IgD.
AB  - The resting population of small surface IgM+ and surface IgD+ B cells from the
      human tonsil can be preactivated by overnight culture in interleukin-4 (IL-4) to
      show locomotor responses to anti-IgM and anti-IgD at between 10 ng and 1
      microgram/ml. Because this locomotion is activated through the antigen receptor
      and may simulate a response to antigen, we set out to establish whether this was
      a chemotactic response using a checkerboard filter assay with a range of
      concentrations and concentration gradients of anti-IgD. At high concentrations
      (100 ng/ml to 1 microgram/ml), a chemokinetic response, but no chemotaxis, to
      anti-IgD was seen. However, in concentration gradients set up at lower
      concentrations (0-50 ng/ml) a chemotactic response was demonstrable. During the
      period of culture in anti-IgD at 1 microgram/ml, a progressive loss of surface
      IgD from the cells was seen, but there was no loss at 10 ng/ml. This receptor
      loss from the cell surface may account for the lack of chemotactic effect of the
      anti-IgD at higher concentrations.

PMID- 8881764
TI  - A defect in inducible beta-galactosidase of B lymphocytes in the osteopetrotic
      (mi/mi) mouse.
AB  - Macrophages were activated by administration of an inflammatory lipid metabolite,
      lysophosphatidylcholine (lyso-Pc), to wild type mice but not murine
      (microphthalmic) osteopetrotic (mi/mi) mutant mice. In vitro treatment of wild
      type mouse peritoneal cells with lyso-Pc efficiently activated macrophages
      whereas lyso-Pc-treatment of mi mutant mouse peritoneal cells resulted in no
      activation of macrophages. Generation of macrophage activating factor requires a
      precursor protein, serum vitamin D binding protein (DBP), and participation of
      lyso-Pc-inducible beta-galactosidase of B lymphocytes. Lyso-Pc-inducible beta
      galactosidase of B lymphocytes was found to be defective in mi mutant mice.

PMID- 8881765
TI  - Isotype and antibody specificity of spontaneously formed immunoglobulins in pig
      fetuses and germ-free piglets: production by CD5- B cells.
AB  - Pig fetuses, colostrum-deprived newborns and germ-free (GF) piglets, animals in
      which B-cell development is not influenced by maternal regulatory factors, were
      employed to study the occurrence and specificity of natural antibodies (NAb).
      Serum immunoglobulins of all isotypes were found in 44-day-old fetuses (the
      gestation period in pigs lasts 114 days) and their level, with predominating IgM,
      was increased during fetal ontogeny. In sera of fetuses at the end of embryonic
      life as well as of newborns and older GF piglets, antibody activity against
      autoantigens (thyroglobulin, hormones, ssDNA), phylogenetically conserved
      proteins (myosin), haptens (trinitrophenyl; TNP) and bacterial components
      (Escherichia coli O86, tetanic anatoxin) was detected by enzyme-linked
      immunosorbent assay. The antigen-biding activity of IgM NAb increased after
      isolation of the serum immunoglobulins on a Staphylococcus Protein A (SPA)
      Sepharose column. IgM reactivity similar to that detected in serum was found in
      supernatants from polyclonally stimulated cultures of spleen of 8- and 12-day-old
      GF piglets. Pig fetal liver IgM+ B cells, which were able to produce IgM after
      polyclonal stimulation, did not express the CD5 molecule. Our results indicate
      that pig preimmune repertoire is comparable to that described in humans and mice,
      although in contrast to these species pig B-1 cells do not express CD5.

PMID- 8881766
TI  - Sequence analysis of rearranged IgVH genes from microdissected human Peyer's
      patch marginal zone B cells.
AB  - The Peyer's patches of the terminal ileum are a source of IgA plasma cells in the
      intestinal lamina propria of experimental animals. They are also thought to
      harbour IgA memory cells. However, the microanatomical location of Peyer's patch
      memory cells, and whether they are also present in man is not known. Human
      Peyer's patches have a pronounced marginal zone (MGZ) of sIgD-negative B cells.
      In this study we analysed the sequence of polymerase chain reaction-amplified,
      rearranged IgVH genes from microdissected MGZ B cells, to determine whether this
      is a site of B-cell memory in Peyer's patches. We observed that the majority of
      Peyer's patch MGZ B cells contain heavily mutated IgVH genes and are therefore
      clearly memory B cells. Sequences of rearranged mutated genes in the MGZ have a
      pattern of replacement and silent mutations expected of selected products of the
      affinity maturation process. Related clones, with identical CDR3 but different
      patterns of mutation, are seen. This suggests that either these memory cells are
      formed as the germinal centre selection process proceeds, or a memory cell has re
      entered the germinal centre for further rounds of mutation. Interestingly, in one
      patient, the MGZ in the Peyer's patches also contains a proportion of B cells
      with unmutated IgVH 4.21 genes.

PMID- 8881767
TI  - Mechanisms by which HLA-class II molecules protect human B lymphoid tumour cells
      against NK- and LAK-mediated cytolysis.
AB  - We have previously shown that mutant B lymphoblastoid cell lines, totally
      deficient in expression of human leucocyte antigen (HLA)-class II molecules, but
      with normal HLA-class I expression, develop enhanced susceptibility to natural
      killer (NK) and lymphokine-activated killer (LAK) cell lysis. The current
      investigations were aimed at examining the role of HLA-DR and native peptides
      occupying the antigen-presenting grooves of HLA-class II molecules in protecting
      mutants of the same B-lymphoid lines against LAK-mediated lysis. No augmentation
      in LAK lysis was observed despite using two mutant B-cell lines (9.22.3 and
      3.1.0) that lacked HLA-DR. Both these lines expressed HLA-DP and HLA-DQ. However,
      when using other B-cell lines with point mutations in certain regions of the HLA
      DR alpha-chain (78, 80 and 96) significantly increased their susceptibility to
      LAK lysis despite normal expression of HLA-DR and the other class I and II
      molecules. Of particular interest was the finding that absence of native peptides
      in antigen-presenting grooves of all the HLA-class II molecules did not render
      the mutant B cell (9.5.3) susceptible to LAK lysis. These observations support
      the concept that there are different NK or LAK clones. Certain LAK clones
      recognize 'self' major histocompatibility complex (MHC) antigens (but not the
      native peptides in their antigen-presenting grooves). Presence of 'self' MHC
      antigens inhibits such clones. Conversely, other NK or LAK clones recognize 'non
      self' in the context of MHC antigens. Hence, point mutations at certain specific
      sites on the MHC molecules or foreign peptides in the antigen-presenting grooves
      enhances the susceptibility of these cells to LAK clones recognizing 'non-self'.

PMID- 8881768
TI  - Immune responses in congenic mice to multiple antigen peptides based on defined
      epitopes from the malaria antigen Pf332.
AB  - Repeat sequences from the Plasmodium falciparum blood stage antigen Pf332
      frequently comprise the pentapeptide VTEEI, an epitope recognized by certain
      parasite neutralizing antibodies. This B-cell epitope was assembled in an
      octavalent multiple antigen peptide (MAP) system either as trimers (VTEEI)3
      (MAP1) or as an integral part of a naturally occurring Pf332 undecamer repeat
      sequence SVTEEIAEEDK (MAP2). Characteristics of the immunogenicity of these
      subunit constructs were evaluated in H-2 congenic mice. MAP1 generated antibody
      responses in mice of the H-2d, H-2k and H-2q haplotypes, but not in H-2b or H-2s
      mice, whereas MAP2 only induced antibodies in mice of H-2k haplotype. When
      analysing T-cell responses induced by the MAP, lymph node cells from responder
      strains primed in vivo with MAP1 proliferated in response to restimulation with
      both MAP1 and the peptide (VTEEI)3. MAP2, however, did not induce a detectable T
      cell proliferation. Additionally, the lack of antibody response to MAP1 in H-2b
      mice could be circumvented by combining the MAP1 peptide and a H-2b-restricted T
      cell epitope in a diepitope MAP construct. Despite the fact that the motif VTEEI
      has not been identified in Pf332 sequences in the form of a trimer, MAP1 did
      induce Pf332 protein-reactive antibodies. Assembly of multimers of short defined
      epitopes in MAP constitutes an interesting approach for the design of polyvalent
      subunit immunogens.

PMID- 8881769
TI  - Crystallization of a complex between the Fab fragment of a human immunoglobulin M
      (IgM) rheumatoid factor (RF-AN) and the Fc fragment of human IgG4.
AB  - Rheumatoid factors (RF) are the characteristic autoantibodies found in patients
      with rheumatoid arthritis. They recognize epitopes in the Fc region of
      immunoglobulin G (IgG) and are often of the IgM isotype. In order to analyse the
      nature of RF-Fc interactions, we have crystallized a complex between the Fab
      fragment of a human monoclonal IgM rheumatoid factor (RF-AN) and the Fc fragment
      of human IgG4. The stoichiometry of the complex within the crystals was found to
      be 2:1 Fab:Fc. The crystals diffracted X-rays to 0.3 nm resolution, and the space
      group was C2, with cell dimensions a = 16.03 nm, b = 8.19 nm, c = 6.42 nm, beta =
      98.3 degrees. We have also determined the sequence of the variable region of the
      RF-AN light chain, not hitherto reported. This belongs to the V lambda III-a
      subgroup and is closely related to the germline gene Humlv318, from which it
      differs in three amino acid residues. This is the first reported crystallized
      complex between a human autoantibody and its autoantigen.

PMID- 8881771
TI  - Synthesis of classical pathway complement components by chondrocytes.
AB  - Using immunohistochemical studies, C1q, C1s, C4 and C2 were detected in
      chondrocytes in normal human articular cartilage and macroscopically normal
      articular cartilage from the inferior surfaces of hip joints of patients with
      osteoarthritis. Using reverse-transcribed polymerase chain reaction (RT-PCR),
      mRNA for C1q, C1s, C4 and C2 was also detected in RNA extracted from articular
      cartilage. C1r, C3, C1-inhibitor, C4-binding protein and factor I were not
      detected by either technique. Articular chondrocytes cultured in vitro
      synthesized C1r, C1s, C4, C2, C3 and C1-inhibitor but not C1q, C4-binding protein
      or factor I, as assessed by enzyme-linked immunosorbent assay (ELISA) and
      Northern blot analysis. Thus cultured articular chondrocytes have a complement
      profile that is similar to that of cultured human fibroblasts rather than that of
      articular chondrocytes in vivo. Complement synthesis in cultured chondrocytes was
      modulated by the cytokines interleukin-1 beta (IL-1 beta), tumour necrosis factor
      alpha (TNF-alpha) and interferon-gamma (IFN-gamma), showing that cytokines can
      probably regulate complement synthesis in intact cartilage. The possible roles of
      local synthesis of complement components by chondrocytes in matrix turnover and
      the regulation chondrocyte function are discussed.

PMID- 8881770
TI  - Differential effects of osteopontin on the cytotoxic activity of macrophages from
      young and old mice.
AB  - Osteopontin (OPN) is a secreted phosphoprotein found in body fluids (e.g. plasma,
      urine, milk) and in mineralized tissues. Its expression is increased in many
      transformed cells and in normal cells exposed to various cytokines. When
      stimulated with the inflammatory mediators lipopolysaccharide and interferon
      gamma, mouse macrophages secrete nitric oxide (NO) as a cytotoxic agent effective
      against microbial invaders and tumour cells. This report documents (1) that
      thioglycollate-elicited peritoneal macrophages, activated with the inflammatory
      mediators, produced less NO and exhibited reduced cytotoxicity towards target
      cells when they were obtained from old animals than when they were obtained from
      young animals; and (2) that OPN was able to inhibit both the induced NO synthesis
      and cytotoxicity, but more effectively in macrophages from the young animals than
      those from the old animals. This may be due to the observed higher level of OPN
      expression in macrophages from old animals.

PMID- 8881772
TI  - Hormones and the cytoskeleton of animals and plants.
AB  - It is often overlooked that a cell can exert its specific functions only after it
      has acquired a specific morphology: function follows form. The cytoskeleton plays
      an important role in establishing this form, and a variety of hormones can
      influence it. The cytoskeletal framework has also been shown to function in a
      variety of cellular processes, such as cell motility (important for behavior),
      migration (important for the interrelationship between the endocrine and immune
      systems, e.g., chemotaxis), intracellular transport of particles, mitosis and
      meiosis, maintenance of cellular morphology, spatial distribution of cell
      organelles (e.g., nucleus and Golgi system), cellular responses to membrane
      events (e.g., endocytosis and exocytosis), intracellular communication including
      conductance of electrical signals, localization of mRNA, protein synthesis, and-
      more specifically in plants--ordered cell wall deposition, cytoplasmic streaming,
      and spindle function followed by phragmoplast function. All classes of hormones
      seem to make use of the cytoskeleton, either during their synthesis, transport,
      secretion, degradation, or when influencing their target cells. In this review
      special attention is paid to cytoskeleton-mediated effects of selected hormones
      related to growth, transepithelial transport, steroidogenesis, thyroid and
      parathyroid functioning, motility, oocyte maturation, and cell elongation in
      plants.

PMID- 8881773
TI  - Twisted liquid crystalline supramolecular arrangements in morphogenesis.
AB  - Supramolecular assemblies following liquid crystalline cholesteric geometries
      have been described in biological systems from optical properties observed in
      polarized-light microscopy and structural data obtained in electron microscopy.
      Major biological macromolecules are discussed, including structural polymers of
      the extracellular matrix, genetic material in nuclei and chromosomes, and
      proteins of the cytoplasm. The liquid crystalline assembly properties of
      biological polymers have been demonstrated by experiments in vitro with molecules
      at basic structural levels, such as molecular chains of cellulose and chitin,
      triple helices of collagen, and double helices of DNA, and also with entities at
      higher states of organization as they appear in cells and tissues, such as
      cellulose and chitin crystallites, and collagen fibrils. It appears that the
      building of cellular and extracellular edifices implies self-ordering processes
      of the liquid crystalline type and that the study of these mesomorphic states
      will help resolve basic questions about the structure and morphogenesis of
      densely packed biological structures.

PMID- 8881774
TI  - Vitellogenin receptors: oocyte-specific members of the low-density lipoprotein
      receptor supergene family.
AB  - Receptors that transport vitellogenin (VTG) into oocytes are of vital importance
      to egg-laying species, because they mediate a key step of oocyte maturation, a
      prerequisite to reproduction. Vitellogenins are lipophosphoglycoproteins that are
      produced under female hormonal control in large central organs (fat body in
      insects; liver in higher animals) and are transported in the circulation to the
      female gonads. VTG receptors localized in coated pits on the surface of growth
      competent oocytes are able to accumulate in the yolk high concentrations of VTG
      and other ligands they recognize. The study of VTG receptors and their ligands
      has identified genes that specify related ligands, and a family of receptors. To
      date, all molecularly characterized VTG receptors belong to the low-density
      lipoprotein receptor supergene family, which ranges from a 600-kDa receptor in
      Caenorhabditis elegans to the 100-kDa so-called very-low-density lipoprotein
      receptors in mammals. These receptors, by and large, recognize ligands with
      similarities in structural elements first defined in the human apoplipoproteins B
      100 and E. Recent studies on the receptor family have added VTG and lipoprotein
      lipase to the list of co-evolved ligands and have revealed that VTG receptors are
      able to interact with ligands other than VTG and also with some unrelated to
      lipoprotein metabolism. For example, the chicken VTG receptor also imports very
      low-density lipoprotein, riboflavin-binding protein, and alpha-2-macroglobulin
      into growing oocytes. Such multifunctionality of receptors is likely the result
      of evolutionary pressure to provide the female germ cell with a highly economical
      machinery for vitellogenesis.

PMID- 8881775
TI  - Follicular dendritic cells and germinal centers.
AB  - Follicular dendritic cells (FDCs) are stromal cells unique to primary and
      secondary lymphoid follicles. Recirculating resting B cells migrate through the
      FDC networks, whereas antigen-activated B cells undergo clonal expansion within
      the FDC networks in a T cell-dependent fashion, thereby generating germinal
      centers. Here, B cells undergo somatic mutation, positive and negative selection,
      isotype switching and differentiation into high-affinity plasma cells and memory
      B cells. Since the discovery of FDCs by electron microscopy as long-term antigen
      retaining cells 30 years ago isolation of FDCs and generation of FDC-like cells
      lines and of FDC-specific monoclonal antibodies have been achieved. FDCs express
      all three types of complement receptors as well as Ig-Fc receptors, through which
      antigen-antibody immune complexes are retained. However, the mechanism that
      prevents FDCs from internalizing the antigens and retaining them in native form
      for long periods of time remains obscure. Substantial evidence derived from
      cultures in vitro indicates that FDCs contribute directly to the survival and
      activation of peripheral B cells. The adhesion between FDCs and B cells is
      mediated by ICAM-1 (CD54)-LFA-1(CD11a) and VCAM-VLA-4. T cells may interact with
      FDCs in a CD40/CD40-ligand-dependent fashion. Whether FDCs originate from
      hematopoietic progenitors or from stromal elements is still a controversy. New
      evidence suggests the presence of two types of dendritic cells within human
      germinal centers: (i) the classic FDCs that express DRC-1, KiM4, and 7D6 antigens
      represent stromal cells; and (ii) the newly identified CD3-CD4-CD11c- germinal
      center dendritic cells (GCDC) represent hematopoietic cells that may be analogous
      to the antigen-transporting cells described in mice. Finally, FDCs appear to be
      involved in the growth of follicular lymphomas and in the pathogenesis of HIV
      infection.

PMID- 8881776
TI  - Cell biology of kidney glomerulus.
AB  - It has been accepted that some artifacts are inevitably produced by the
      conventional preparation steps for electron microscopy, including fixation,
      dehydration, embedding, ultrathin sectioning, and staining. Therefore,
      conventional ultrastructural findings on kidney glomeruli are hardly thought to
      be correlated with the physiological functions of kidneys in vivo. In this
      chapter, two preparation techniques, the quick-freezing and deep-etching (QF-DE)
      method or the quick-freezing and freeze-substitution (QF-FS) method, are
      presented and shown to be useful for clarifying the ultrastructures of kidney
      glomeruli more closely to structures in vivo with fewer artifacts. Moreover, the
      ultrastructures of glomerular capillary loops have been demonstrated by a new "in
      vivo cryotechnique," that shows that hemodynamic factors should be considered in
      the morphological study of glomerular functions.

PMID- 8881777
TI  - Distribution and functions of parathyroid hormone-related protein in vertebrate
      cells.
AB  - Parathyroid hormone-related protein (PTHrP) was isolated from tumors and
      identified as the agent of humoral hypercalcemia of malignancy (HHM) in 1987.
      Since then its gene structure in several mammalian and an avian species has been
      analyzed and its gene expression demonstrated in many adult and embryonic tissues
      derived from all three germ layers. The composition and structure of PTHrP
      peptide depends on both differential gene splicing and posttranslational
      processing, which result in a range of peptides of potentially diverse functions.
      This chapter describes the distribution of PTHrP in both normal and neoplastic
      adult and embryonic tissues. PTHrP is of fundamental importance to cell survival
      because the absence of the gene is fatal; this aspect of PTHrP function in cell
      physiology becomes overwhelmingly important in neoplasia. Intracrine or paracrine
      actions for PTHrP seem to be most likely in mammalian and avian physiology, but
      in fishes high circulating levels suggest classic endocrine functions as well.
      Much remains to be learned of the biology of this fascinating protein.

PMID- 8881778
TI  - The tuberous breast deformity: classification and treatment.
AB  - To date there are many descriptive terms for the tuberous breast deformity but
      there is no widely accepted nomenclature. A retrospective study was undertaken of
      68 tuberous breasts and the operative corrections performed. The deformities were
      classified into four types. Type I (hypoplasia of the lower medial quadrant),
      type II (hypoplasia of the lower medial and lateral quadrants, sufficient skin in
      the subareolar region), type III (hypoplasia of the lower medial and lateral
      quadrants, deficiency of skin in the subareolar region) and type IV (severe
      breast constriction, minimal breast base). Areolar prolapse, usually regarded as
      a major symptom, was only found in 30 (44%) deformed breasts. Postoperative
      review of 51 breasts in 31 patients showed that type I cases treated by reduction
      mammaplasty of adequately sized breasts or augmentation of hypoplastic breasts
      had excellent results. These procedures with additional spreading of the breast
      tissue in type II deformities give good results. Severe cases (types III and IV)
      treated by augmentation and tissue spreading procedures have an unsatisfactory
      shape and have a 'second crease' deformity. For types III and IV, additional skin
      in the subareolar region by tissue expansion or flap procedures is necessary.
      There is no one method to correct 'the' tuberous breast but there are many
      procedures which should be used according to the type of deformity. The
      classification developed could end the confusion in nomenclature.

PMID- 8881779
TI  - A review of 120 Becker permanent tissue expanders in reconstruction of the
      breast.
AB  - In reconstructive breast surgery, the permanent tissue expander has become
      popular because it avoids expander-implant exchange and gives the patient some
      control over the final breast size. It may, however, be associated with a number
      of complications. We therefore analysed the clinical notes of 111 consecutive
      recipients of Becker breast expanders with respect to complications and their
      possible predisposing factors. 120 prostheses were inserted in 111 consecutive
      patients with a mean age of 42.6 years. Median follow-up was 12 months (range 8
      to 22). The commonest indication was postmastectomy breast reconstruction (81%)
      followed by congenital hypoplasia (14%) and acquired breast asymmetry following
      repeated biopsies (3%). Overexpansion before size adjustment was achieved after
      an average of 8 expander inflations. Complications included capsular contracture
      (9%), local tumour recurrence (8%), wound dehiscence (8%), filling port failure
      (6%), infected prostheses (4.5%) and ruptured implants (1.6%). The significant
      predisposing factors to wound dehiscence/infection were heavy smoking and
      radiotherapy (P < or = 0.05, chi 2 test). Expansion rate was not a factor. 89% of
      patients expressed satisfaction with the final aesthetic result. Despite the
      excellent results obtained with this technique, caution must be exercised in
      heavy smokers and the previously irradiated.

PMID- 8881780
TI  - Breast reconstruction with anatomical expanders and implants: our early
      experience.
AB  - Dissatisfied with the upper pole fullness produced by the Becker expander/mammary
      prosthesis, we started using 'anatomically' shaped expanders and implants, as
      described by Maxwell, for breast reconstruction. We reviewed the results of our
      first 24 breast reconstructions in 19 patients, who were deemed suitable for
      reconstruction with this technique between August 1994 and April 1995 (9 months).
      The most commonly used expander was 500 cc (range 400-700 cc) and an average of
      2.73 inflations was required before replacing the expander with a definitive
      implant. The minimum follow-up was 6 months. Few complications were recorded and
      all patients were very happy with the final result. We found that the
      anatomically shaped expanders and implants produced better aesthetic
      reconstructions compared to dome shaped prostheses. Importantly, the procedure
      was technically simple and the results readily reproducible.

PMID- 8881781
TI  - The effect of sphincter pharyngoplasty on the range of velar movement.
AB  - The aim of this study was to assess the mobility of the soft palate following
      sphincter pharyngoplasty in patients with velopharyngeal incompetence of variable
      aetiology. Pre- and postoperative videotape recordings of lateral view
      videofluoroscopy of 24 patients were retrospectively studied and compared with
      regard to the range of velar movement. Tracings of the velopharyngeal port were
      made on acetate paper directly from the television monitor and absolute angle
      measurements were taken. Analysis of the results showed a highly significant
      increase in the range of palatal movement postoperatively. There was no evidence
      of correlation between the magnitude of the increase and the postoperative
      improvement in speech. The findings and their implications are discussed.

PMID- 8881782
TI  - An objective assessment of speech and swallowing following free flap
      reconstruction for oral cavity cancers.
AB  - In this prospective study, eight consecutive patients underwent excision of oral
      cavity cancer and reconstruction with a microvascular free flap. Six patients had
      one pre- and two postoperative assessments of speech and swallowing at four to
      six weeks and four to six months respectively. One patient could not attend for
      the preoperative assessment and another for the first postoperative assessment.
      The speech assessment consisted of an intelligibility score and an articulation
      score. The swallowing assessment consisted of a videofluoroscopic examination.
      Five patients had an excellent postoperative speech assessment score, two had a
      moderate and one a poor result. Videofluoroscopy demonstrated minor swallowing
      problems preoperatively in one patient. Postoperatively, three patients had
      severe or moderate loss of control of bolus. Significant aspiration was detected
      in two and mild aspiration in one patient at the second postoperative assessment.
      The abnormalities of speech and swallowing were minor in the majority of the
      patients and the overall outlook was good. This information should be of value
      for preoperative counselling.

PMID- 8881783
TI  - Petrosectomies for invasive tumours: surgery and reconstruction.
AB  - Tumours involving the temporal bone have historically carried a bad prognosis.
      The only prospect of cure is radical en bloc resection. Temporal bone resection
      for malignancies is, however, such a formidable undertaking that many centres
      label such tumours as unresectable. Additionally, the enormity of the surgical
      defect poses a major reconstructive challenge. A review of 14 petrosectomies (in
      12 males and 2 females) performed for extensively invasive neoplasms in and
      around the ear is presented. All underwent immediate reconstruction, the majority
      (12/14) with free tissue transfers. 9 of the 14 patients (64%) are still alive
      after a mean follow-up of 70 months (range 4-8 years). With the use of free
      tissue transfers, an aggressive approach with regard to the resection margins can
      safely be adopted in the full knowledge that the eventual size of the defect need
      not compromise tumour clearance. Additionally, free flaps provided a reliable
      dural seal. This approach of radical en bloc resection with free flap
      reconstruction has decreased the mortality (compared to the literature), while
      largely reducing the morbidity to that of unavoidable cranial nerve resection.

PMID- 8881784
TI  - The influence of maxillary dentures on mid-facial fracture patterns.
AB  - The presence of upper arch dentures modifies fracture patterns occurring in mid
      facial trauma. The fracture patterns of 16 upper denture wearers suffering
      maxillary fractures were retrospectively studied. Mid-facial fractures in this
      group were predominantly of the Le Fort I type and in 14 patients demonstrated an
      atypical fracture path with a vertical fracture passing from the main Le Fort I
      fracture to the inferior orbital rim. Full upper arch dentures generally
      protected the upper alveolus from fracture but, where there was discontinuity of
      the prosthesis, alveolar fractures mirroring the edge of the denture as it
      crossed the alveolar region were seen. These findings should alert the clinician
      to the possibility of unusual maxillary fractures in denture wearers and aid our
      understanding of fracture patterns in the mid-facial skeleton.

PMID- 8881785
TI  - The distally based superficial sural flap for reconstruction of the lower leg and
      foot.
AB  - We describe our experience with the use of distally based superficial sural flaps
      for coverage of defects in the lower leg and foot in 21 patients. In 18 patients
      the flap was successfully transferred, in 2 cases partial necrosis of the flap
      occurred and 1 flap failed completely. In 18 cases the flap was used as a
      fasciocutaneous flap and in 3 cases as a fascial flap only. The advantages of
      this flap are: easy and quick dissection, hence saving operating time, minimal
      morbidity of donor site and preservation of major arteries of the leg. Although
      the flap was described as reliable for covering defects around the ankle joint,
      we have been able to cover defects of the dorsum of the foot distally and up to
      the mid-third of the tibia proximally.

PMID- 8881786
TI  - Adipofascial flap of the lower leg based on the saphenous artery.
AB  - The adipofascial flap of the lower leg based on the saphenous artery is a
      modification of the saphenous artery flap. It has been used successfully in 5
      patients for reconstruction of soft tissue defects around the knee and superior
      third of the tibia. The size of these flaps ranged from 5 x 12 cm to 5 x 18 cm.
      All flaps survived completely. These cases had minimal donor site morbidity
      because their donor sites were closed primarily with the preserved overlying
      skin.

PMID- 8881787
TI  - Free arterialised venous forearm flaps for limb reconstruction.
AB  - Arterialised venous flaps are an alternative method to conventional flaps.
      Arterialised venous flaps include only the venous network and afferent blood
      comes from the arterial system. Arterialised venous flaps have been mostly used
      for closure of small defects. We have designed an arterialised venous flap
      utilising the venous network of the forearm and applied this flap in 5 patients
      with various defects in the extremities ranging in size from 6 x 8 cm to 10 x 12
      cm. Four flaps totally survived. One flap had 30% partial necrosis. Overall
      clinical results were successful. The free arterialised venous forearm flap
      provides large, thin, good quality tissue with less morbidity at the donor site
      without sacrificing one major artery of the hand and can be an alternative for
      the conventional radial forearm flap.

PMID- 8881788
TI  - Flexor carpi radialis opponensplasty.
AB  - Although numerous opponensplasties are described, the options are limited when
      the median and ulnar nerves and the flexor tendons are injured. We describe a new
      tendon transfer using the previously injured flexor carpi radialis combined with
      a fascia lata graft for opponensplasty in a patient who had a wrist injury
      resulting in division of all his flexor tendons, except flexor carpi ulnaris, and
      the median and ulnar nerves.

PMID- 8881789
TI  - The use of pH adjusted lignocaine in controlling operative pain in the day
      surgery unit: a prospective, randomised trial.
AB  - We report the results of a randomised, case matched, controlled, double blind
      study on 40 patients undergoing correction of their prominent ears, comparing
      efficacy of pH adjusted lignocaine to lignocaine alone in controlling operative
      pain. Each patient received commercial lignocaine in one ear and the same
      preparation reconstituted with 1 ml of 8.4% sodium bicarbonate in the other ear
      according to our randomisation protocol. 30 patients were studied to compare the
      difference between the buffered and commercial preparation infiltrated at room
      temperature. A further 10 patients were studied to assess the benefit the
      buffered preparation at room temperature had over commercial lignocaine warmed to
      body temperature. Linear analogue pain scores for discomfort at infiltration and
      during the operation itself were analysed. Buffered lignocaine imparts a
      significant reduction in pain on infiltration, compared to the commercial
      preparation at both room and body temperature. Both preparations were equally
      effective in obliterating pain during the operation itself.

PMID- 8881790
TI  - Recurrence of thin melanoma: how effective is follow-up?
AB  - In order to assess the benefit to patients with thin malignant melanoma (< 0.76
      mm) of a 5-year clinical follow-up programme, we have studied 602 patients with a
      minimum time from primary surgery of 5 years. Tumour recurrence occurred in 24
      patients (4% of all patients) but only five surgically treatable recurrences (<
      1% of all patients) occurred within the 5-year period following primary surgery.
      After 5 years there were four surgically treatable recurrences, but their
      prognosis was generally poor. The remaining cases of tumour recurrence were not
      surgically treatable. In the face of an increasing incidence of melanoma, and the
      accompanying increase in demand for surgical treatment and outpatient review, we
      question the need for prolonged hospital follow-up of thin melanoma.

PMID- 8881791
TI  - Micrographic surgery for subungual squamous cell carcinoma.
AB  - Eight patients were treated for subungual squamous cell carcinoma (4 female, 4
      male; mean age 61 years). History of disease ranged from 9 months to 14 years
      (mean 4.7 years). Outpatient surgery under local anaesthetic was performed using
      Mohs micrographic surgery and formalin-fixed histological specimens. Tumour
      clearance was achieved after 2-6 procedures (median 3) over a mean period of 6.9
      days. In all cases the wounds were allowed to heal by secondary intention and the
      distal phalanx was preserved. During a mean follow-up period of 3.1 years (range
      0.5-6), no recurrence was seen and involved digits remained functional. Mohs
      micrographic surgery can provide a valuable alternative to amputation for
      subungual squamous cell carcinoma.

PMID- 8881792
TI  - Laser treatment for an unusual reactive vascular proliferation.
AB  - An unusual case of severe vascular proliferation presenting in the form of
      haemorrhaging cutaneous lesions on the leg is reported. The similarity between
      these benign lesions and various malignancies is outlined. The patient healed
      well when the lesions were excised using a laser under local anaesthetic.

PMID- 8881793
TI  - The combined costal cartilage and rectus abdominis myocutaneous free flap.

PMID- 8881794
TI  - Cool perfusion solutions for skin flaps.

PMID- 8881795
TI  - A perfusion solution containing an antithrobotic agent and an oxygen free radical
      scavenger has a beneficial effect on postischaemic oedema and skin flap survival.

PMID- 8881796
TI  - Keloid of the penis after circumcision.

PMID- 8881797
TI  - Hydrogen sulphide: a bacterial toxin in ulcerative colitis?

PMID- 8881798
TI  - Oesophageal cancer is an uncommon cause of death in patients with Barrett's
      oesophagus.
AB  - BACKGROUND: Barrett's oesophagus carries a 30-fold to 40-fold increased risk of
      oesophageal cancer. It is unknown whether endoscopic surveillance programmes
      reduce mortality from oesophageal cancer. METHODS: A cohort study was undertaken
      of all 166 patients in whom the diagnosis Barrett's oesophagus had been
      established between 1973 and 1986. RESULTS: One hundred and fifty five of 166
      patients could be traced (93%). During a mean follow up of 9.3 years (amounting
      to 1440 patient years) eight patients had developed oesophageal cancer at random
      intervals (one case in 180 patient years). All but one of the tumours were
      diagnosed at endoscopy for symptoms, three in the stage of carcinoma in situ.
      Risk factors for the development of oesophageal cancer were extensive Barrett's
      oesophagus exceeding 10 cm (p = 0.02) and Barrett's ulcer at the time of intake
      (p = 0.009). Seventy six patients were alive; three had undergone surgery for
      oesophageal cancer and were without recurrence respectively, 12.8 years, 12.1
      years, and 7 months postoperatively. Seventy nine patients had died; five of them
      had developed oesophageal cancer, but in only two cases this had been the cause
      of death (2.5%). CONCLUSIONS: Oesophageal cancer is an uncommon cause of death in
      patients with Barrett's oesophagus. The patients of this cohort would not have
      benefited from an endoscopic surveillance programme.

PMID- 8881799
TI  - Risk factors of oesophageal perforation during pneumatic dilatation for
      achalasia.
AB  - BACKGROUND/AIMS: Pneumatic dilatation of the oesophagus is a well established
      treatment for achalasia. Oesophageal perforation is the most serious complication
      that occurs in 2% to 6% of cases. The aim of this retrospective survey was to
      identify predictive risk factors for perforation in a consecutive series of 218
      patients with achalasia. METHODS: Between 1983 and 1993, 270 pneumatic
      dilatations were performed in 218 patients. A Witzel dilator was used in 58 cases
      and a Rigiflex dilator in 212. Eight oesophageal perforations occurred (3%). The
      clinical, radiological, endoscopic, manometric, and technical data for the eight
      perforated patients were compared with those of 30 patients randomly sampled
      among those without perforation. RESULTS: All perforations occurred during the
      first dilatation. Perforations were fewer during dilatations with the Rigiflex
      dilator than with the Witzel dilator (2.4% v 5.2%). Perforations were all located
      above the cardia, on the left side of the oesophagus. In a multivariate analysis,
      a small weight loss and a high amplitude of oesophageal contractions in the group
      of patients with perforations were predictive of complications (respectively, p =
      0.001 and p = 0.026). A contraction amplitude higher than 70 cm H2O in the lower
      part of the oesophagus was observed in three of eight patients with perforations
      but was not seen in any of the 30 patients without perforation (p < 0.01).
      CONCLUSIONS: This identification of risk factors should facilitate the choice
      between pneumatic dilatation or a surgical approach.

PMID- 8881800
TI  - Decreased plasma isoleucine concentrations after upper gastrointestinal
      haemorrhage in humans.
AB  - BACKGROUND: A decrease in arterial isoleucine values after intragastric blood
      administration in pigs has been observed. This contrasted with increased values
      of most other amino acids, ammonia, and urea. After an isonitrogenous control
      meal in these pigs all amino acids including isoleucine increased, and urea
      increased to a lesser extent, suggesting a relation between the arterial
      isoleucine decrease and uraemia after gastrointestinal haemorrhage. METHODS: To
      extend these findings to humans, plasma amino acids were determined after
      gastrointestinal haemorrhage in patients with peptic ulcers (n = 9) or
      oesophageal varices induced by liver cirrhosis (n = 4) and compared with
      preoperative patients (n = 106). RESULTS: After gastrointestinal haemorrhage,
      isoleucine decreased in all patients by more than 60% and normalised within 48
      hours. Most other amino acids increased and also normalised within 48 hours.
      Uraemia occurred in both groups, hyperammonaemia was seen in patients with liver
      cirrhosis. CONCLUSIONS: These results confirm previous findings in animals and
      healthy volunteers that plasma isoleucine decreases after simulated upper
      gastrointestinal haemorrhage. This supports the hypothesis that the absence of
      isoleucine in blood protein causes decreased plasma isoleucine values after
      gastrointestinal haemorrhage, and may be a contributory factor to uraemia and
      hyperammonaemia in patients with normal and impaired liver function,
      respectively. Intravenous isoleucine administration after gastrointestinal
      haemorrhage could be beneficial and will be the subject of further research.

PMID- 8881801
TI  - Helicobacter pylori infection in children: relation with current household living
      conditions.
AB  - BACKGROUND: Studies demonstrating that deprived household living conditions
      during childhood are risk factors for acquisition of Helicobacter pylori
      infection have been performed mainly in adults, who probably acquired the
      infection several decades ago. This study investigates whether deprived household
      living conditions remain important risk factors for infection in subjects
      (children) with recently acquired infection. AIMS: To examine the relation
      between current household living conditions and acquisition of H pylori infection
      in childhood. SUBJECTS/SETTING: Opportunistically recruited group of 367
      children, aged 3 to 15 years, undergoing routine non-gastrointestinal day
      surgery. METHODS: Anti-H pylori IgG antibodies measured by a commercial enzyme
      linked immunosorbent assay validated for use in children. Postal questionnaire
      collecting sociodemographic data and data on household living conditions.
      RESULTS: Infection was associated with social class and overcrowding in the
      household. After adjustment for age, social class, and household density, a
      positive association remained between infection with H pylori and bed-sharing
      between children and parents on one or two nights per week, odds ratio for
      infection (95% CI), 2.29 (1.21, 4.32) or more frequently, odds ratio for
      infection (95% CI), 2.95 (1.35, 6.45). CONCLUSIONS: The continuing importance of
      household living conditions in the acquisition of H pylori infection is confirmed
      and household crowding and sharing a bed with a parent are identified as risk
      factors for infection.

PMID- 8881802
TI  - Role of Helicobacter pylori in ulcer healing and recurrence of gastric and
      duodenal ulcers in longterm NSAID users. Response to omeprazole dual therapy.
AB  - BACKGROUND: The relation between Helicobacter pylori infection and non-steroidal
      anti-inflammatory drug (NSAID)-associated peptic ulcers remains unclear; in
      particular, it is not known whether H pylori plays a part in the healing and
      recurrence of these ulcers. AIMS: To evaluate prospectively in a consecutive
      series of arthritis patients receiving longterm NSAID treatment the prevalence of
      peptic ulcer as well as the effect of H pylori eradication on the healing and
      recurrence of gastric and duodenal ulcer found. PATIENTS: Some 278 consecutive
      patients underwent gastroscopy with multiple biopsies of the gastric antrum and
      corpus for histological examination and rapid urease test. One hundred peptic
      ulcers (59 gastric ulcers, 39 duodenal ulcers, and two gastric ulcers concomitant
      with a duodenal ulcer) were found. Seventy per cent of these ulcers were H pylori
      positive. METHODS: According to their H pylori status, ulcer patients were
      randomised to one of the following treatments: H pylori negative ulcers received
      omeprazole 20 mg twice daily for four to eight weeks, whereas H pylori positive
      lesions were treated with omeprazole 20 mg twice daily plus amoxycillin 1 g twice
      daily (the second of these for the first two weeks) or omeprazole alone for four
      to eight weeks while continuing NSAID therapy. Patients with healed ulcers were
      endoscopically followed up for six months after stopping antiulcer therapy while
      continuing NSAIDs. RESULTS: Endoscopic healing rates for gastric and duodenal
      ulcers in the three different groups were similar both at four and eight weeks. H
      pylori eradication did not influence healing, which occurred in 14 of 20 (70%) of
      patients in whom H pylori was eradicated, compared with 14 of 17 (82%) of
      patients with persistent infection. Cumulative recurrence rates at six months did
      not statistically differ among the three different groups (27% in H pylori
      negative, 46% in H pylori positive, and 31% in those where H pylori was
      eradicated during the healing phase), although a numerical trend in favour of a
      higher recurrence rate in infected patients was evident. CONCLUSIONS: H pylori
      eradication does not confer any significant advantage on the healing of gastric
      and duodenal ulcers associated with longterm NSAID use. It remains to be
      established with certainty whether eradication may be helpful in the reduction of
      recurrence in a specific subset of NSAID associated ulcer.

PMID- 8881803
TI  - Is saliva serology useful for the diagnosis of Helicobacter pylori?
AB  - BACKGROUND: The Cortecs Diagnostics Helisal Assay test is a quantitative
      immunoassay for salivary IgG antibodies against Helicobacter pylori. Saliva can
      be obtained simply with the kit in the general practitioners surgery. AIMS: To
      compare the new saliva serological test for H pylori with 'gold standard'
      evidence of H pylori infection (antral biopsy specimens for histology, culture,
      and urease test) and a new serum serological test. PATIENTS: Eighty six
      unselected dyspeptic patients undergoing endoscopy. METHODS: Each patient
      provided saliva and serum before endoscopy for H pylori serology, which was
      compared against 'gold standard' evidence of infection. RESULTS: Thirty two
      patients were H pylori positive by the 'gold standard' tests. At a cut off value
      of 0.15 EU/ml the saliva test had a sensitivity of 88% and a specificity of 71%,
      with a negative predictive value of 90%. If patients who were taking omeprazole
      or had recent antibiotics are excluded, the sensitivity is unchanged but the
      specificity increases to 79%. The serum test had a similar sensitivity of 85% but
      better specificity of 78%. CONCLUSION: Serum testing remains the best serological
      test for H pylori in the hospital setting. Saliva testing may have a role in
      epidemiological studies and in screening dyspeptic patients in general practice,
      especially in children in whom venesection is more difficult.

PMID- 8881804
TI  - Vitamin E concentrations in the human stomach and duodenum--correlation with
      Helicobacter pylori infection.
AB  - BACKGROUND: Vitamin E (alpha-tocopherol) is an important endogenous antioxidant
      and may also act as an anticarcinogen. AIM: To determine the vitamin E status of
      subjects with, and without, gastroduodenal inflammation and Helicobacter pylori
      infection. SUBJECTS: 36 patients undergoing routine gastroscopy for investigation
      of dyspepsia. METHODS: High performance liquid chromatography with fluorometric
      detection was used to determine alpha-tocopherol values. RESULTS: In H pylori
      negative subjects with normal gastroduodenal histology (n = 11) median alpha
      tocopherol values (ng/mg tissue weight) were significantly higher in the corpus
      (16.4, interquartile range (IQR) 8.9-22.6) than in the antrum (3.0, IQR 2.6-6.7,
      p = 0.001) or duodenum (6.7, IQR 2.5-8.4, p = 0.001). H pylori infection (n = 19)
      was associated with a reduction in the corpus alpha-tocopherol values (median
      8.3, IQR 4.9-13.7, p < 0.05) but there was no significant change in the antral
      concentrations although this was the main site of inflammation and neutrophil
      activity. Duodenal alpha-tocopherol values were not significantly changed in the
      presence of duodenitis or gastric H pylori infection. alpha-Tocopherol was not
      detected in the gastric juice of any of the subjects. Plasma alpha-tocopherol
      concentrations in the H pylori negative subjects (median 10.4 mg/l, IQR 7.2-11.9)
      were not significantly different to the values in the H pylori positive subjects
      (median 11.1 mg/l, IQR 7.6-12.7). CONCLUSIONS: Concentrations of alpha-tocopherol
      in H pylori negative subjects are higher in the corpus than in the antrum or
      duodenum. In the presence of predominantly antral H pylori infection and
      neutrophil activity the major change seen is a reduction in corpus alpha
      tocopherol values while antral concentrations are maintained. These findings may
      reflect a mobilisation of antioxidant defences to the sites of maximal
      inflammation in the stomach.

PMID- 8881805
TI  - Endoscopic papillectomy: a novel approach to difficult cannulation.
AB  - BACKGROUND: Selective cannulation of the biliary and pancreatic ducts is
      considered to be the most difficult and rate limiting aspect of diagnostic
      endoscopic retrograde cholangiopancreatography (ERCP). AIMS/METHODS: A novel
      technique for difficult cannulation is described and its potential role in
      relieving malignant duodenal obstruction secondary to ampullary carcinoma. A
      diagnostic endoscopic papillectomy was performed in 10 patients in whom previous
      attempts at cannulation had failed. Five patients had exophytic ampullary
      carcinomas, one had carcinoma of the head of pancreas, two had an oedematous
      ampulla secondary to low common bile duct stones, while two had protuberant
      ampullae with ectopic orifices. The technique entails snaring the ampulla flush
      with the duodenal wall using a polypectomy snare and in a similar fashion to
      polypectomy removing the ensnared ampulla with diathermy using a coagulation
      current. The underlying exposed ducts can then be cannulated while the ensnared
      ampulla can be retrieved to aid histological diagnosis. RESULTS: Successful
      cannulation was achieved in all 10 cases with significant haemorrhage in one
      patient (10%). Four of the snared ampullary carcinomas (80%) were retrieved
      enabling a histological diagnosis to be made. CONCLUSIONS: This study
      demonstrates the potential role for endoscopic papillectomy as a means of
      cannulation in difficult circumstances, however larger comparative studies are
      required.

PMID- 8881806
TI  - An impaired phagocytic function is associated with leucocyte activation in the
      early stages of severe acute pancreatitis.
AB  - BACKGROUND: An excessive leucocyte activation takes place early in severe acute
      pancreatitis. Furthermore, some indirect evidences suggest a disturbance of the
      mononuclear phagocytic system in the severe cases. AIMS: To compare the early
      functionalism of leucocytes obtained from patients with mild disease and severe
      disease, under the hypothesis that an impaired phagocytic function could be
      associated with the leucocyte activation. PATIENTS AND METHODS: Flow cytometric
      parameters of leucocyte function, such as phagocytosis, and fluorescence of
      leucocytes with acridine orange (FLAO) were prospectively measured together with
      granulocyte elastase plasma concentrations in 21 patients with severe (n = 7) and
      mild (n = 14) acute pancreatitis. Samples were drawn at 24 hours from admission,
      48 hours, 72 hours, and on day 5. RESULTS: There was a greater leucocyte
      activation together with a deficient phagocytosis before 72 hours in severe
      patients. The results (mean (SEM)) severe v mild were: 440 (115) microgram/l v 77
      (14) micrograms/l for granulocyte elastase, 2.218 (377) v 1.308 (155) for FLAO,
      64 (7) v 90 (2), and 55 (9) v 81 (3) for percentages of phagocytising neutrophils
      and monocytes, respectively. Phagocytic capacity returned to normal later on day
      5. CONCLUSIONS: The excessive leucocyte activation together with the impaired
      phagocytosis could be related to the onset of complications in severe acute
      pancreatitis.

PMID- 8881807
TI  - Factors associated with serum antibodies to reticulin, endomysium, and gliadin in
      an adult population.
AB  - BACKGROUND: Gluten sensitivity is thought to be significantly under-diagnosed in
      the population. AIMS: The aims of this study were to investigate the prevalence
      of antibodies associated with coeliac disease in a large representative sample of
      the adult population and to determine factors that are associated with their
      presence. PATIENTS: Serum samples from 5420 subjects with approximately equal
      numbers in each five year group from ages 15 to 65 years were obtained from the
      Belfast MONICA project and Change of Heart surveys, set up to monitor and assess
      risk factors associated with coronary heart disease in the population. METHODS:
      Using immunofluorescence and enzyme linked immunosorbent assay (ELISA) techniques
      autoantibodies, including those to reticulin, endomysium, and gliadin were
      determined. RESULTS: The results establish that IgA antigliadin antibody
      prevalence is high at 5.7%. Antiendomysial antibody was present in 1.2% of
      samples and gliadin and endomysial antibodies in 0.4%. No significant differences
      were found between men and women, area of residence in Northern Ireland or the
      year of sampling over the eight year period. However, there was a significant
      increase in the prevalence of IgA gliadin antibody, and to a lesser extent IgA
      endomysial antibody, with increasing age. CONCLUSION: The high prevalence of
      these positive antibodies suggests that coeliac disease may be relatively common
      in Northern Ireland.

PMID- 8881808
TI  - Allopurinol and glutamine attenuate bacterial translocation in chronic portal
      hypertensive and common bile duct ligated growing rats.
AB  - BACKGROUND: Spontaneous bacterial infections and septicaemia result in morbidity
      and mortality in patients with portal hypertension and obstructive jaundice. AIM:
      The aim of this study in rats was to investigate the incidence of bacterial
      translocation in portal hypertension and obstructive jaundice, and to evaluate
      the effects of allopurinol and glutamine. METHODS: Rats were subjected to sham
      laparotomy (SL), portal hypertension (PH) by calibrated stenosis of the portal
      vein, and common bile duct ligation (CBDL). Animals of each group were either
      treated with allopurinol (50 mg/kg twice a week), glutamine (1 g/kg/d), and
      allopurinol and glutamine. RESULTS: After four weeks, significant bacterial
      translocation in the untreated PH and CBDL rats occurred. Intestinal mucosal
      malondialdehyde concentrations (MDA), as an indicator for lipid peroxidation, and
      myeloperoxidase activity (MPO) released from activated neutrophils were also
      significantly increased (p < 0.01). Allopurinol and glutamine in PH and CBDL rats
      improved bacterial translocation, and decreased MDA and MPO values (p < 0.01).
      CONCLUSION: In PH and CBDL rats significant bacterial translocation, ileal
      mucosal lipid peroxidation, and neutrophil derived MPO activity occurred.
      Allopurinol and glutamine significantly reduced bacterial translocation, as well
      as ileal mucosal MDA and MPO activities.

PMID- 8881809
TI  - Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a
      prospective randomised double blind study.
AB  - BACKGROUND: Gastric and duodenal bacterial overgrowth frequently occurs in
      conditions where diminished acid secretion is present. Omeprazole inhibits acid
      secretion more effectively than cimetidine and might therefore more frequently
      cause bacterial overgrowth. AIM: This controlled prospective study compared the
      incidence of gastric and duodenal bacterial overgrowth in patients treated with
      omeprazole or cimetidine. METHODS: 47 outpatients with peptic disease were
      randomly assigned to a four week treatment regimen with omeprazole 20 mg or
      cimetidine 800 mg daily. Gastric and duodenal juice were obtained during upper
      gastrointestinal endoscopy and plated for anaerobic and aerobic organisms.
      RESULTS: Bacterial overgrowth (> or = 10(5) cfu/ml) was present in 53% of the
      patients receiving omeprazole and in 17% receiving cimetidine (p < 0.05). The
      mean (SEM) number of gastric and duodenal bacterial counts was 6.0 (0.2) and 5.0
      (0.2) respectively in the omeprazole group and 4.0 (0.2) and 4.0 (0.1) in the
      cimetidine group (p < 0.001 and < 0.01; respectively). Faecal type bacteria were
      found in 30% of the patients with bacterial overgrowth. Basal gastric pH was
      higher in patients treated with omeprazole compared with cimetidine (4.2 (0.5)
      versus 2.0 (0.2); p < 0.001) and in patients with bacterial overgrowth compared
      with those without bacterial overgrowth (5.1 (0.6) versus 2.0 (0.1); p < 0.0001).
      The nitrate, nitrite, and nitrosamine values in gastric juice did not increase
      after treatment with either cimetidine or omeprazole. Serum concentrations of
      vitamin B12, beta carotene, and albumin were similar before and after treatment
      with both drugs. CONCLUSIONS: These results show that the incidence of gastric
      and duodenal bacterial overgrowth is considerably higher in patients treated with
      omeprazole compared with cimetidine. This can be explained by more pronounced
      inhibition of gastric acid secretion. No patient developed signs of malabsorption
      or an increase of N-nitroso compounds. The clinical significance of these
      findings needs to be assessed in studies with long-term treatment with
      omeprazole, in particular in patients belonging to high risk groups such as HIV
      infected and intensive care units patients.

PMID- 8881810
TI  - Adult coeliac disease and cigarette smoking.
AB  - BACKGROUND: Genetic predisposition and gliadin exposure are known to be crucial
      factors in the development of coeliac disease. Circumstantial evidence suggests
      that other unidentified environmental factors may also be of pathogenetic
      importance. AIM: To define the relation between cigarette smoking and the risk of
      development of symptomatic adult onset coeliac disease. SUBJECTS: Eighty six
      recently diagnosed adult coeliac disease patients and 172 controls matched for
      age and sex. METHOD: Matched case control study, using a simple questionnaire to
      determine smoking history, and in particular smoking status at the time of
      diagnosis of coeliac disease. RESULTS: At the time of diagnosis, the proportion
      of current smokers was 7% in the coeliac group, and 32.6% in the control group,
      giving a matched odds ratio of 0.15 (95% confidence intervals 0.06, 0.38). The
      difference could not be accounted for by social class, nor by coeliac patients
      giving up smoking after the onset of symptoms as most non-smokers in the coeliac
      group had never smoked. CONCLUSION: Cigarette smoking, or a factor closely linked
      to it, seems to exert a major protective effect against the development of
      symptomatic adult onset coeliac disease. The implication is that gliadin exposure
      is not the only important environmental factor involved in the pathogenesis of
      this condition.

PMID- 8881811
TI  - Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and
      rectal foam administration.
AB  - BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective
      medications for refractory inflammatory bowel disease. However, use of these
      drugs has been limited by concerns about their toxicity. Colonic delivery of
      azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To
      determine the bioavailability of 6-mercaptopurine after administration of
      azathioprine via three colonic delivery formulations. METHODS: Twenty four
      healthy human subjects each received 50 mg of azathioprine by one of four
      delivery formulations (each n = 6): oral; delayed release oral; hydrophobic
      rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose
      of intravenous azathioprine during a separate study period. Plasma concentrations
      of 6-mercaptopurine were determined by high pressure liquid chromatography.
      RESULTS: The bioavailabilities of 6-mercaptopurine after colonic azathioprine
      administration via delayed release oral, hydrophobic rectal foam, and hydrophilic
      rectal foam (7%, 5%, 1%; respectively) were significantly lower than the
      bioavailability of 6-mercaptopurine after oral azathioprine administration (47%)
      by Wilcoxon rank sum pairwise comparison. CONCLUSIONS: Azathioprine delivered to
      the colon by delayed release oral and rectal foam formulations considerably
      reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of
      these colonic delivery methods, which can potentially limit toxicity by local
      delivery of high doses of azathioprine, should be investigated in patients with
      inflammatory bowel disease.

PMID- 8881812
TI  - Association of HLA class II genes with susceptibility to Crohn's disease.
AB  - BACKGROUND: Published studies on the association between HLA class II genes and
      inflammatory bowel disease are contradictory perhaps because of the limited size
      and ethnic heterogeneity of the populations studied. AIM: To compare the
      frequencies of HLA class II genes in a large number of French patients with
      Crohn's disease and in an ethnically matched control group. METHODS: 344 patients
      (196 F, 148 M, mean age 23.6 years) with Crohn's disease were molecularly
      genotyped for the HLA-DQB1 and DRB1 alleles. The results were compared with those
      for an ethnically matched control population of 488 white adults. RESULTS: There
      were two significant variations of alleles at the DQB1 locus: an increase in
      DQB1*0501 allele frequency (chi 2 = 10.6, corrected p value (pc) = 0.01, odds
      ratio (OR) = 1.61) and a decrease in DQB1*0602/0603 allele frequencies (chi 2 =
      8.43, pc = 0.037, OR = 0.66). DRB1 analysis showed associations with three
      allelic variations: an increase in the frequencies of DRB1*01 (chi 2 = 12.86, pc
      = 0.003, OR = 1.75) and DRB1*07 alleles (chi 2 = 11.18, pc = 0.008, OR = 1.58)
      and a very significant decrease in that of the DRB1*03 allele (chi 2 = 19.7, pc =
      9.10(-5), OR = 0.46). CONCLUSION: The alleles DRB1*01 and DRB1*07 are associated
      with susceptibility to Crohn's disease. The strong negative association between
      the DRB1*03 allele and Crohn's disease suggests that the HLA-DRB1*03 allele
      mediates 'resistance' to Crohn's disease.

PMID- 8881813
TI  - Autoantibodies and immunoglobulins in collagenous colitis.
AB  - BACKGROUND: The aetiology and pathogenesis of collagenous colitis are unknown.
      Autoimmunity has been suggested, but no serological findings have supported such
      a theory. AIMS AND METHODS: Serum from 38 collagenous colitis patients and 38
      matched healthy controls was analysed for autoantibodies--that is, antinuclear
      antibodies, antineutrophil cytoplasmic antibodies, smooth muscle and
      mitochondrial antibodies, rheumatoid factor and antibodies to thyroglobulin and
      microsomal antigen, together with antibodies to endomysium, gliadin, and
      cardiolipin. The serum values of IgA, IgG, IgM, and IgG-subclasses, and
      complement factors C3 and C4 were also determined. RESULTS: In patients with
      collagenous colitis the mean value of IgM was significantly increased 2.5 g/l
      (95% CI; 1.9, 3.2) compared with 1.4 g/l (95% CI; 1.2, 1.7) in controls (p =
      0.002). Antinuclear antibodies occurred in nine of 38 patients compared with
      three of 38 controls, this difference was not statistically significant (p =
      0.11). The results of all other immunoglobulins, complement factors, and specific
      antibodies showed no statistical difference between patients and controls.
      CONCLUSIONS: No firm evidence for an autoimmune genesis in collagenous colitis is
      found in this study, although the findings of a positive ANA-titre in some
      patients and an increased IgM level might give some support for this hypothesis.

PMID- 8881814
TI  - Methionine derivatives diminish sulphide damage to colonocytes--implications for
      ulcerative colitis.
AB  - BACKGROUND: Bacterial production of anionic sulphide is increased in the colon of
      ulcerative colitis and sulphides can cause metabolic damage to colonocytes. AIMS:
      To assess the reversal of the damaging effect of sulphide to isolated colonocytes
      by methionine and methionine derivatives. METHODS AND SUBJECTS: Isolated
      colonocytes were prepared from rat colons and 12 human colectomy specimens. In
      cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate
      (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect
      of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL
      methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was
      observed. RESULTS: In rat colonocytes sodium hydrogen sulphide dose dependently
      reduced oxidative metabolite formation from n-butyrate, an action reversed in
      order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine
      S-methyl-sulphonium chloride > L-methionine. In human colonocytes S
      adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2
      production (p = < 0.005) suppressed by sodium hydrogen sulphide. CONCLUSION:
      Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency
      of sulphide detoxification may be an important factor in the pathogenesis and
      treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane
      disulphonate may be of therapeutic value.

PMID- 8881815
TI  - Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A
      placebo controlled one year study.
AB  - BACKGROUND AND AIMS: To evaluate the efficacy and safety of the topical
      corticosteroid budesonide, given in an oral controlled release formulation for
      maintenance of remission in patients with ileal and ileocaecal Crohn's disease
      (CD). PATIENTS AND METHODS: Out of 176 patients with active CD who had achieved
      remission (CD activity index score < or = 150) after 10 weeks' treatment with
      either budesonide or prednisolone, 90 were randomised to continue with once daily
      treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months
      in a double blind, multicentre trial. Time to symptomatic relapse was calculated
      using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic
      visits and a corticotropin stimulation test was performed after three months of
      treatment. RESULTS: Thirty two patients were allocated to the 6 mg budesonide
      group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19
      per cent of the patients in the 6 mg group had relapsed, compared with 45 per
      cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The
      corresponding results after 12 months was 59 per cent in the 6 mg budesonide
      group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p =
      0.44). The median time to relapse or discontinuation was 258 days in the 6 mg
      group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021).
      Mean morning plasma cortisol values increased from entry in all three groups with
      no statistically significant differences at 12 months. All 13 patients remaining
      in the placebo group after three months had a normal corticotropin stimulation
      response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg
      budesonide groups (p = 0.14). Acne and moon face were slightly more common in the
      budesonide groups. CONCLUSION: 6 mg budesonide once daily is significantly more
      efficacious than placebo in prolonging time to relapse in CD, and causes only
      minor systemic side effects.

PMID- 8881816
TI  - Promotion of colorectal neoplasia in experimental murine ulcerative colitis.
AB  - BACKGROUND: The mechanisms underlying the frequent development of colorectal
      carcinomas in patients with ulcerative colitis are still unknown. AIMS: To
      evaluate whether mucosal necrosis and regeneration act as enhancing or promoting
      factors in colorectal tumorigenesis, development of multiple colorectal tumours
      was studied in a murine model of ulcerative colitis with azoxymethane
      pretreatment. METHODS: Periods of chronic ulcerative colitis in mice were induced
      by three repeated administrations of 3% dextran sulphate sodium subsequent to a
      single azoxymethane pretreatment, to give conditions similar to the clinically
      observed active and remission phases. RESULTS: In the chronic colitis group with
      carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the
      colorectum. This occurred primarily on the left side of the large intestine or
      transverse colon, the sites of the most severe colitic injury. The observed
      lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell
      proliferation was evidenced by high uptake of bromodeoxyuridine, and increased
      activities of thymidylate synthetase and thymidine kinase. No tumours were
      induced in the control groups with azoxymethane pretreatment or chronic colitis
      alone. CONCLUSIONS: Repeated mucosal erosion with necrosis and regeneration is
      critical for the development of colorectal tumours in this experimental colitis
      system.

PMID- 8881817
TI  - Nitric oxide donating compounds stimulate human colonic ion transport in vitro.
AB  - BACKGROUND: Nitric oxide (NO) has been recently implicated as a possible mediator
      of bowel inflammation and has also been shown to stimulate electrogenic chloride
      secretion in rat and guinea pig intestine. This study therefore investigated the
      effect on two NO donors, sodium nitroprusside (SNP) and S-nitroso-N
      acetylpenicillamine (SNAP) on human colonic ion transport. METHODS: Changes in
      short circuit current (delta SCC) in response to nitric oxide donating compounds
      were measured in muscle stripped normal human colon mounted in Ussing chambers.
      The ion species and intracellular mechanisms responsible for delta SCC evoked by
      SNP were investigated. RESULTS: Basolateral SNP caused a progressive rise in
      delta SCC over the range 10(-7) to 10(-4)M (ED50 = 2.5 x 10(-5)M). SNAP 10(-4)M
      also evoked a qualitatively similar delta SCC compared with SNP 10(-4)M.
      Basolateral SNP evoked a greater delta SCC than apical and this was significantly
      attenuated by bumetanide 10(-4)M (52.9 +/- 10.1%) and in chloride free media
      (68.3 +/- 7.3%). delta SCC response to SNP was not significantly changed by
      basolateral 4-acetamido-4'-isothio-cyano-2,2'disulphonic acid stillbene (SITS 10(
      3)M) an inhibitor of sodium/bicarbonate exchange, or apical amiloride 10(-5)M an
      inhibitor of sodium absorption. SNP induced delta SCC was also significantly
      reduced by piroxicam (mean (SEM)) 10(-5)M (57.9 (11.9)%), nordihydroguaretic acid
      10(-4)M (48.0 (12.9)%), tetrodotoxin (TTX 10(-6)M, 52.3 (9.1)%), and practically
      abolished by TTX and piroxicam together (96.8 (3.3)%). CONCLUSION: NO donors
      stimulate human colonic ion transport in vitro. For SNP, increased delta SCC is
      at least due in part to chloride secretion, and the response seems to be
      transduced through enteric nerves and by local prostanoid synthesis. This study
      provides evidence that NO may be another important mediator of ion transport in
      human colon.

PMID- 8881818
TI  - High intracolonic acetaldehyde values produced by a bacteriocolonic pathway for
      ethanol oxidation in piglets.
AB  - BACKGROUND: Human colonic contents and many colonic microbes produce considerable
      amounts of acetaldehyde from ethanol in vitro. AIMS: To examine in piglets if
      acetaldehyde is produced in the colon also in vivo, and if so, what is the fate
      of intracolonically formed acetaldehyde. ANIMALS: Seventeen native, non-fasted
      female piglets (20-25 kg) were used. METHODS: Six piglets received either 1.5
      g/kg bw or 2.5 g/kg bw of ethanol intravenously. In seven piglets, 0.7 g or 1.75
      g of ethanol/kg bw was administered intravenously, followed by a subsequent
      intragastric ethanol infusion of 1.8 g/kg bw and 4.5 g/kg bw, respectively. The
      samples of colonic contents for the assessment of ethanol and acetaldehyde
      concentrations were obtained up to seven hours. In four additional piglets, the
      intracolonic values of ethanol, acetaldehyde, and acetate were observed for 60
      minutes after an intracolonic infusion of acetaldehyde solution. RESULTS: A
      raised intracolonic, endogenous acetaldehyde concentration (mean (SEM); 36 (9)
      microM) was found in all piglets before ethanol infusion. After the infusion of
      ethanol, intracolonic ethanol and acetaldehyde values increased in parallel,
      reaching the peak values 57 (4) mM of ethanol and 271 (20) microM of acetaldehyde
      in the group that received the highest dose of ethanol. A positive correlation (r
      = 0.45; p < 0.001) was found between intracolonic ethanol and acetaldehyde
      values. Acetaldehyde administered intracolonically was mainly metabolised to
      acetate but also to ethanol in the colon. CONCLUSIONS: Significant endogenous
      intracolonic acetaldehyde values can be found in the normal porcine colon.
      Furthermore, our results suggest the existence of a bacteriocolonic pathway for
      ethanol oxidation. Increased amounts of acetaldehyde are formed intracolonically
      from ingested ethanol by this pathway.

PMID- 8881819
TI  - Risk of colorectal adenomas in patients with a family history of colorectal
      cancer: some implications for screening programmes.
AB  - BACKGROUND AND AIMS: Most colorectal cancers (CRC) arise in colorectal adenomas.
      A case-control study was conducted to see whether a family history of CRC is
      associated with a higher prevalence of colorectal adenomas. SUBJECTS: Subjects
      were drawn from all patients who underwent colonoscopy at the Royal Brisbane
      Hospital between 1980-1982 and 1985, and included 141 cases with colorectal
      adenomas diagnosed at colonoscopy and 882 controls who were free of polyps at
      colonoscopy. METHODS: The prevalence of family history of CRC was compared
      between patients with adenomas and negative colonoscopy controls. RESULTS:
      Overall, patients with one first degree relative with CRC were at no greater risk
      for adenomas at colonoscopy than patients with no family history (odds ratio (OR)
      = 0.8, 95% confidence intervals (CI) = 0.4, 1.5). Patients with two or more
      affected first degree relatives had a more than doubled risk for adenomas (OR =
      2.3, 95% CI = 0.5, 8.2), and were also more likely to carry moderately or
      severely dysplastic adenomas (OR = 14.1, 95% CI = 2.0, 62.9). CONCLUSIONS: These
      findings are consistent with the hypothesis that some families, in addition to
      those with familial adenomatous polyposis, have an increased susceptibility to
      develop colorectal adenomas, and that adenomas in such families may have a
      greater tendency to undergo malignant transformation.

PMID- 8881820
TI  - How well does stool form reflect colonic transit?
AB  - BACKGROUND: Watery stools are equated with rapid and hard stools with slow
      intestinal transit; however, the relation between stool form and transit through
      specific regions of the gut is not clear cut. In addition, more information is
      needed on interindividual variability of these measurements. AIM: To examine the
      relations between stool form and gastric emptying, small bowel and colonic
      transit. METHODS: Regional gut transit was assessed scintigraphically and
      segmental colonic transit was also quantified by radio-opaque markers. On two
      occasions, 32 healthy volunteers (12 men, 20 women) were studied, women during
      the follicular and luteal phases of menstruation, men twice within a similar four
      week period. Diets were standardised and stool form was recorded on a seven point
      scale. RESULTS: Women had significant harder stools; hard stools were correlated
      significantly with slow transit and loose stools with fast transit through the
      colon. CONCLUSIONS: Stool form could not be related to gastric emptying or small
      bowel transit.

PMID- 8881821
TI  - Divergent patterns of matrix metalloproteinase activity during wound healing in
      ileum and colon of rats.
AB  - BACKGROUND: Uncontrolled and increased extracellular matrix degradation during
      early anastomotic repair in the intestine may reduce wound strength increasing
      the risk of anastomotic dehiscence. AIMS: To characterise the metalloproteinases
      present in intact and anastomosed ileum and colon to study their role in matrix
      degradation after surgery. SUBJECTS: Tissue extracts of uninjured, and of
      anastomosed rat ileum and colon at postoperative days 1, 2, 3, 7, and 90, were
      used. METHODS: Metalloproteinases were identified by gelatin and casein
      zymography. Aminophenylmercuric acetate (APMA) treatment was used to activate
      latent metalloproteinases. RESULTS: Both uninjured ileum and colon contained a 60
      and 67 kDa activity, but a 54 and 72 kDa gelatinase was present in ileum only,
      and a 51 kDa activity in colon only. APMA treatment converted the 60 kDa protease
      to 54 and 51 kDa forms and the 72 kDa protease to the 67 kDa form. These
      gelatinases may correspond to latent and active forms of MMP 1 and MMP 2,
      respectively. Additional metalloproteinases were observed after anastomotic
      construction. Both ileum and colon contained 95 and 230 kDa gelatinases, which
      were converted to 83 and 76 kDa forms by APMA. They may be the latent and active
      forms of MMP 9, respectively. Gelatinolytic activities of 25 and 28 kDa were only
      found in anastomosed ileum. Caseinolytic activities were only found in ileum
      extracts and those were most prominent at day 1, 2, and 3 after surgery.
      CONCLUSIONS: The metalloproteinase pattern in ileum and colon differ considerably
      suggesting that matrix degradation after anastomotic construction may also vary.

PMID- 8881822
TI  - Disturbed anal sphincter function following vaginal delivery.
AB  - BACKGROUND: Recently interest in idiopathic (neurogenic) faecal incontinence has
      swung from denervation of the external anal sphincter to the internal sphincter.
      AIMS: To evaluate the effects of vaginal delivery on the internal sphincter.
      SUBJECTS: 1372 mothers were studied antenatally and 1202 were accepted into the
      study. METHODS: Sphincter pressures were measured antenatally, in the early
      postnatal period, and six to 10 weeks later in selected patients. RESULTS: 755 of
      1202 subjects assessed antenatally were primiparous women and 447 multiparous
      women. Some 320 previous spontaneous vaginal deliveries (SVD) (mean 59 mm Hg) and
      67 previous forceps deliveries (mean 58 mm Hg) had lower resting pressures than
      755 primiparous women (mean 66 mm Hg) (p < 0.01). A total of 493 subjects were
      reassessed postnatally. There were 372 SVDs, 47 vacuum extractions, 20 forceps,
      and 54 caesarean deliveries. All vaginal deliveries but not caesarean sections
      dropped their resting anal pressures from antenatal values (p < 0.001). Some 227
      first SVDs had a much greater fall than 145 subsequent SVDs. In 162 subjects who
      had undergone their first vaginal delivery and who were followed up there was
      some recovery but the resting pressures were still lowered at six to 10 weeks
      post partum. CONCLUSIONS: The first vaginal delivery causes a permanent lowering
      of resting anal pressures. The possible reasons for this are discussed.

PMID- 8881823
TI  - Autonomic control of colonic tone and the cold pressore test.
AB  - BACKGROUND: Cardiovascular responses to cold stimulation are well characterised.
      It is unclear, however, whether cold pain stimulates responses in colonic tone in
      the transverse and sigmoid regions. AIMS: To assess the effects of cold
      stimulation on tone nd motility in the transverse and sigmoid colon and on
      cardiovascular autonomic activity. METHODS: Phasic and tonic motility of the
      transverse and sigmoid colon, pulse rate, and beat to beat pulse variability
      (which are measures of centrally mediated changes in autonomic function) were
      measured before, during, and after a standard cold pressor test in 22 healthy
      volunteers. RESULTS: Cold pain induced a significant increase in colonic tone but
      not phasic contractility in the transverse and sigmoid regions. Simultaneously,
      cold pain increased pulse interval variability. CONCLUSION: The findings are
      consistent with the hypotheses that cold pain produces coactivation of both the
      sympathetic and parasympathetic limbs of the autonomic nervous system and that
      cold induced changes in colonic tone are temporally associated with alterations
      in central autonomic nervous activity.

PMID- 8881825
TI  - Intestinal immunisation with Escherichia coli protects rats against Escherichia
      coli induced cholangitis.
AB  - BACKGROUND: Cholangitis, an infection of the biliary tract, is most commonly
      caused by Gram negative bacteria, particularly Escherichia coli. Factors
      governing the severity of cholangitis, including the role of biliary IgA, are
      poorly understood. AIMS: The aim of this work was to find out if biliary IgA
      directed against E coli protects rats against hepatobiliary infection with E
      coli. SUBJECTS: Male Sprague-Dawley rats weighing 270-350 grams were used in all
      of the experiments. METHODS: At laparotomy, rats were immunised by injecting
      killed E coli or normal saline (controls) into Peyer's patches. With or without
      subsequent antigenic boosting (by oral administration of killed E coli), bile was
      collected at a second laparotomy, and rats were infected by introducing viable E
      coli into the bile duct. Production of IgA anti-E coli antibody was measured by
      enzyme linked immunosorbent assay of bile, and the presence of hepatobiliary
      infection was determined by quantitative culture of liver homogenates. RESULTS:
      Systemic infection was present in six of 12 control rats and in one of 24
      immunised rats (p = 0.005) after death. There was an inverse correlation between
      immunisation and E coli colony counts in cultured liver homogenates (p = 0.024).
      CONCLUSION: The findings suggest that biliary IgA directed against E coli
      protected rats against hepatobiliary E coli infection and systemic sepsis.

PMID- 8881824
TI  - Double blind, placebo controlled food reactions do not correlate to IgE allergy
      in the diagnosis of staple food related gastrointestinal symptoms.
AB  - BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal
      tract are poorly understood. There is conflicting evidence in the literature on
      the role for IgE mediated allergy in gastrointestinal reactions to staple foods.
      AIM: The aim was therefore to study the role of IgE mediated allergy in a group
      of patients with a history of gastrointestinal symptoms related to staple foods
      (cows' milk, hens' egg, wheat and rye flour) verified in double blind placebo
      controlled challenges (DBPCFC). PATIENTS: Fifteen patients with DBPCFC,
      identified by screening of 96 consecutive patients referred to our allergy clinic
      for investigation of suspected gastrointestinal symptoms due to staple foods.
      METHODS: The screening included diaries as well as elimination diets and open and
      blinded food challenges. The frequency of atopy were compared between the double
      blind positive and double blind negative patients. RESULTS: The positive DBPCFC
      in the 15 patients included eight patients with milk intolerance, four with wheat
      flour, two with egg, and one with rye flour. There was no indications of an
      allergic pathogenesis in all 15 patients with positive DBPCFC, as the skin prick
      test and radioallergosorbent test were negative for the relevant allergens. The
      frequency of atopy was four of 21 (19%) in the double blind negative group and
      three of 15 (20%) in the double blind positive group. CONCLUSION: In adult
      patients with staple food induced gastrointestinal symptoms, objectively verified
      by DBPCFC, there were no indications of IgE mediated allergy to the relevant
      foods suggesting other mechanisms in adults than in children. Future studies may
      include measures of local events in the shock organs in relation to food intake,
      for instance utilising inflammatory markers in jejunal fluids.

PMID- 8881826
TI  - Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary
      cirrhosis and its relation to prognostic models.
AB  - BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (31P
      MRS) provides biochemical information about phosphorus metabolism. AIM: To assess
      31P MRS as a prognostic marker in patients with primary biliary cirrhosis (PBC)
      in relation to the current clinical prognostic models. PATIENTS AND METHODS:
      Twenty three patients with PBC of varying functional severity and 16 matched
      healthy volunteers were studied using in vivo 31P MRS. Spectra were acquired
      using a 1.5 T spectroscopy system. Peak area ratios of phosphomonoesters (PME),
      inorganic phosphate (Pi), and phosphodiesters (PDE) and nucleotide triphosphate
      (NTP) were calculated. Pugh score, Christensen prognostic index, and R value
      according to the Mayo model were calculated from the clinical data. RESULTS: The
      PME/NTP, Pi/NTP, PME/PDE, and PME/Pi ratios and the PME signal height ratio (SHR)
      were significantly higher, while the PDE/NTP and PDE/SHR were significantly lower
      in PBC patients compared with healthy volunteers (p < 0.01). Significant
      correlations were seen between PME/Pi ratio and the prognostic index according to
      Christensen (r = 0.63, p < 0.001), R value according to the Mayo model (r = 0.45,
      p < 0.03), and with the Pugh score (r = 0.55, p < 0.007). CONCLUSIONS: This study
      shows that PME/Pi ratio obtained from 31P MRS correlates well with all three of
      the commonly used models of prognosis in patients with PBC. A longitudinal study
      with larger number of patients is required to confirm these findings and
      elucidate the biochemical changes underlying this phenomenon.

PMID- 8881827
TI  - Measles viral genomic sequences in intestinal tissue.

PMID- 8881828
TI  - Oesophageal hypersensitivity.

PMID- 8881829
TI  - Standard 12-lead electrocardiographic diagnosis for identifying the culprit
      artery in inferior wall acute myocardial infarction showing ST segment elevation
      in the inferior leads.

PMID- 8881830
TI  - The clinical spectrum and prognosis of native valve infective endocarditis in non
      addicts.

PMID- 8881831
TI  - Syndrome X: can the puzzle be unravelled?

PMID- 8881832
TI  - Does oestrogen replacement therapy improve exercise capacity and myocardial
      ischaemia?

PMID- 8881833
TI  - Stress echocardiography: the scourge of subjective interpretation.

PMID- 8881834
TI  - Heart rate variability and inappropriate sinus tachycardia after high frequency
      ablation: sign of the injured autonomic nervous system?

PMID- 8881835
TI  - The clinical impact of coronary artery disease; are subjective measures of health
      status more relevant than laboratory-assessed exercise tolerance?

PMID- 8881836
TI  - Percutaneous mitral valvuloplasty: a decade of experience.

PMID- 8881837
TI  - The role of basic arrhythmia research. The continued need for experiments in the
      intact heart and organism.

PMID- 8881838
TI  - Utilization of oxygen by the contractile apparatus is disturbed during
      reperfusion of post-ischaemic myocardium.
AB  - Post-ischaemic ventricular function remains depressed (= myocardial stunning)
      despite nearly normal coronary blood flow during reperfusion. In order to
      illuminate the causes of this phenomenon, we studied the relationship between
      ventricular function and myocardial oxygen consumption (MVO2tot) in experiments
      on 15 isolated rabbit hearts perfused with erythrocyte suspension (hct = 30%).
      Left ventricular systolic function was assessed by measuring aortic flow (ml.min
      1), peak systolic pressure (LVPmax), dP/dtmax, and early relaxation in terms of
      dP/dtmin during control and 30 min after the onset of reperfusion, following 20
      min global no-flow ischaemia. The pressure-volume area was calculated as a
      measure of total mechanical energy. The external mechanical efficiency (Eext) was
      assessed from stroke work and MVO2tot. Both contractile efficiency (Econ =
      inverse slope of the MVO2-PVA relationship) and MVO2 of the unloaded contracting
      heart (MVO2unl = basal MVO2 + MVO2 for excitation-contraction coupling) were
      calculated using pressure-volume area and MVO2tot. RESULTS: At matched heart rate
      (149 +/- 30 vs 147 +/- 31 min-1; mean +/- SD) and end-diastolic volume (1.3 +/-
      0.2 ml), the systolic variables were significantly decreased in the stunned
      myocardium: aortic flow: 38 +/- 13 vs 9 +/- 11 ml.min-1, LVPmax: 112 +/- 19 vs 74
      +/- 18 mmHg, and dP/dtmax: 1475 +/- 400 vs 1075 +/- 275 mmHg.s-1. Likewise,
      dP/dtmin was significantly impaired (-1275 +/- 250 vs -975 +/- 250). The decrease
      in pressure-volume area (570 +/- 280 vs 270 +/- 200 mmHg.ml.100 g-1) was not
      statistically significant. In contrast, both Eext (0.75 +/- 0.29 vs 0.18 +/- 0.26
      arbitrary units) and Econ (31 +/- 18 vs 14 +/- 7%) were significantly decreased,
      whereas MVO2tot (40 +/- 9 vs 34 +/- 8 microliters.beat-1.100 g-1) and MVO2unl (26
      +/- 9 vs 22 +/- 6 microliters.beat-1.100 g-1) were not. SUMMARY: Ventricular
      function after brief episodes of ischaemia is decreased whereas MVO2tot is
      maintained, i.e. external efficiency is decreased. MVO2 for the unloaded
      contraction remained unchanged, indicating that MVO2 for excitation-contraction
      coupling is inappropriately high for the depressed contractile state. The
      decreased contractile efficiency indicates further that O2 utilization of the
      contractile apparatus is disturbed during reperfusion.

PMID- 8881839
TI  - Functional and ultrastructural alterations of canine myocardium subjected to very
      brief coronary occlusions.
AB  - The effects of very brief and recurrent coronary occlusions on myocardial
      regional shortening and its ultrastructure have been analysed. Ultrasonic
      crystals were implanted in the left ventricular subendocardium of 23
      anaesthetized dogs with the thorax open, to measure the shortening fractions of
      an ischaemic and a control segment. Twenty 2 min total occlusions were provoked
      in the left anterior descending coronary artery, with 3 min recovery intervals
      (reperfusion) between occlusions. The shortening fraction decreased progressively
      with each occlusion, reaching a value 18.9% lower than the basal after the last
      ischaemic episode (P < 0.05); 32.3% after 4 h of reperfusion (P < 0.01), and
      28.6% after 24 h (P < 0.01). Qualitative and quantitative ultrastructural
      analysis showed an increase in the mitochondrial volume of the ischaemic tissue
      (158% vs control, P < 0.001) with significant damage to the cell components (7.7
      fold increases vs control mitochondria). These results show that when the
      myocardium is subjected to very brief and repeated coronary occlusions, there is
      progressive deterioration of systolic function with structural alterations,
      mainly at the mitochondrial level. These modifications are still observable 24 h
      after the end of ischaemic stimulation and could be the cause of transitory
      and/or chronic systolic dysfunctions in the absence of previous heart attack.

PMID- 8881840
TI  - Atherogenic risk reduction in patients with dyslipidaemia. comparison between
      bezafibrate and lovastatin.
AB  - OBJECTIVE: To examine the atherogenic risk-reducing effect of bezafibrate and
      lovastatin. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Double-blind, randomized
      clinical trial of male and female patients with moderate hypercholesterolaemia
      with or without hypertriglyceridaemia. Two months dietary treatment followed by
      400 mg sustained release bezafibrate every day or 20 mg lovastatin every day for
      6 months. Patients recruited (n = 561) and treated (n = 524) by primary care
      physicians throughout Austria. MAIN OUTCOME MEASURES: Multifactorial assessment
      of atherogenic risk profile. RESULTS: Bezafibrate increased high density
      lipoprotein cholesterol by 16%, lovastatin by 10% (P < 0.05). Bezafibrate
      decreased low density lipoprotein cholesterol by 20%, lovastatin by 27% (P <
      0.001). Bezafibrate decreased total cholesterol by 15%, lovastatin by 18% (P <
      0.001). Bezafibrate reduced triglycerides by 29%, lovastatin by 13% (P < 0.001);
      and fibrinogen by 9.4% and 3.0%, respectively. Fibrinogen reduction as a result
      of bezafibrate administration was dependent on starting levels. The risk ratio
      cholesterol:high density lipoprotein cholesterol (baseline both 6.1) reduction
      was 27% in both groups. The low:high density lipoprotein ratio (baseline:
      4.1/4.2) reduction reached 31% and 34% respectively. Coronary events' probability
      (calculated from multifactorial risk functions) were greatly reduced by both
      agents (41%/33%). Hypertriglyceridaemic patients had a higher initial global
      coronary risk and profited more from treatment. Bezafibrate was significantly
      better tolerated (P < 0.001) than lovastatin; most events were gastrointestinal
      (6 vs 14, ns) or as a result of creatine phosphokinase elevations (3 vs 12, P <
      0.05). CONCLUSIONS: Both treatments significantly reduced the risk parameters for
      developing coronary heart disease, and calculated multifactorial coronary risk
      was similarly decreased. When selecting a drug for moderate dyslipidaemia and if
      haemostatic regulation is disturbed, the additional effect of bezafibrate on
      elevated fibrinogen levels should be considered.

PMID- 8881841
TI  - Thrombolytic therapy for evolving myocardial infarction needs an approach that
      integrates benefit and risk.
AB  - Thrombolytic therapy is a major step forward in the treatment of acute myocardial
      infarction and results in substantial reduction of mortality. However, in
      individual patients the benefits and bleeding risk are difficult to estimate,
      especially when benefit seems small or outweighed by the risk of intracranial
      bleeding. For this and other reasons less than half the patients with evolving
      myocardial infarction are treated with thrombolytic therapy. We propose to
      approach the decision 'to treat or not to treat' in a systematic way, integrating
      estimated benefit and intracranial bleeding risk in individual patients.
      According to a decision-model developed with currently available medical
      knowledge, thrombolytic therapy appears beneficial in the majority of patients
      with evolving myocardial infarction provided that ST segment elevation is present
      and treatment can be started within 12 h of onset of symptoms. Thrombolytic
      therapy is warranted in the absence of risk factors for intracranial haemorrhage,
      even if the risk of cardiac death in the first year without thrombolytic therapy
      is as low as 2.3% (patients with small inferior wall infarctions). For patients
      with increased intracranial bleeding risk, the cardiac baseline risk without
      thrombolytic therapy and treatment delay become important variables to take into
      account when selecting thrombolytic therapy. Precise thresholds for these
      variables are presented.

PMID- 8881842
TI  - Reproducibility of digital exercise echocardiography.
AB  - We determined the intra, inter-observer and temporal variability of upright
      bicycle exercise echocardiography in 50 consecutive patients with suspected
      coronary heart disease. Using significant artery stenoses as reference, the
      sensitivity of digital exercise echocardiography was 89% and the specificity 92%.
      Regarding the presence or absence of exercise-induced ischaemia, intra-observer
      agreement was 86% (73-94% with 95% confidence limits, kappa value (K) 0.70 (0.50
      0.91)). Inter-observer agreement between two independent observers was 92 (81
      98)% (K = 0.81 (0.63-0.99)). Temporal variability was examined by repeating
      exercise echocardiography after one week in 30 stable patients; it demonstrated
      90 (78-97)% agreement (K = 0.71 (0.40-1.00)). The inter-observer agreement
      appeared to be lower in patients or myocardial segments with wall motion
      abnormalities at rest (86% and 82%, respectively) than in patients or segments
      with normal myocardial function at rest (96% and 94%, respectively); ns, P <
      0.05, respectively). Analysis of specific regions showed a significantly higher
      level of agreement (P < 0.05) regarding exercise-induced ischaemia in segments
      supposed to be supplied by the circumflex branch of the left coronary artery
      (96%) than in the perfusion bed of the left anterior descending branch (87%) and
      right coronary artery (88%). Comparing estimated values of echocardiographic
      ejection fraction, analysis of intra-observer variability showed a correlation
      coefficient of 0.91 and 95% confidence limits of a single estimate of ejection
      fraction of +/- 10.3%. Corresponding analyses of inter-observer and temporal
      variability showed correlation coefficients of 0.93 and 0.84, respectively, and
      95% confidence limits of single estimates of ejection fraction of +/- 9.6% and +/
      13.0%, respectively. Thus, the diagnostic result and the reproducibility of
      digital exercise echocardiography are satisfactory and comparable with those
      obtained by myocardial scintigraphy. However, approximately 10% of the
      examination results may be reversed when the test is repeated or reevaluated by
      the same or by another observer. The result seems to be less reproducible in
      patients with abnormal wall motion at rest than in patients with normal
      myocardial function before exercise.

PMID- 8881843
TI  - Good exercise capacity at hospital discharge predicts recovery of baroreflex
      sensitivity after myocardial infarction.
AB  - Myocardial infarction results in depressed baroreflex sensitivity, which has been
      shown to be associated with increased risk of ventricular arrhythmias and sudden
      death. We measured baroreflex sensitivity in 37 patients with acute myocardial
      infarction before hospital discharge and 3 months after the infarction to find
      out whether the baroreflex sensitivity recovers during that period. In addition,
      baroreflex sensitivity was assessed in 15 healthy controls. Baroreflex
      sensitivity was assessed from the regression line relating the change in R-R
      interval to the change in systolic blood pressure following an intravenous bolus
      injection of phenylephrine. There was a wide inter-individual variation in the
      change of baroreflex sensitivity (delta baroreflex sensitivity) in infarction
      patients, but the average baroreflex sensitivity showed no significant change
      during the 3-month follow-up (10.2 + 5.6 to 11.8 +/- 7.5 ms.mmHg-1, ns) and
      remained lower than the baroreflex sensitivity of the controls (16.4 +/- 9.7
      ms.mmHg-1, P < 0.05). delta Baroreflex sensitivity correlated significantly with
      exercise capacity measured before hospital discharge. When the patients were
      divided into tertiles according to the delta baroreflex sensitivity (-3.3 +/- 1.5
      ms.mmHg-1 in the lowest tertile, 1.0 +/- 1.0 ms.mmHg-1 in the middle tertile and
      7.5 +/- 4.0 ms.mmHg-1 in the highest tertile) the exercise capacity was found to
      increase from the lowest to the highest tertile (exercise time 357 +/- 115 s, 418
      +/- 126 s and 461 +/- 141 s, respectively; P < 0.05 lowest vs highest tertile).
      Patients with a low exercise tolerance (exercise time < 360 s) showed a
      significantly smaller delta baroreflex sensitivity than patients with a good
      exercise tolerance (exercise time > or = 480 s) (-0.5 +/- 4.4 vs 5.3 +/- 5.4
      ms.mmHg-1, P < 0.05), respectively. delta Baroreflex sensitivity was not related
      to the location or type of infarction, thrombolytic therapy, presence of angina
      pectoris or left ventricular function at the time of discharge. In conclusion,
      exercise capacity assessed before hospital discharge seems to be a predictor of
      baroreflex sensitivity recovery in patients with a recent myocardial infarction.

PMID- 8881844
TI  - Clinical predictors of unstable coronary lesion morphology.
AB  - We evaluated prospectively clinical and angiographic data in 400 patients, 200
      with unstable and 200 with stable angina in order to determine which clinical
      markers could reliably predict unstable coronary artery lesions. Comparison of
      the angiogram of 200 patients with unstable and 200 with stable angina revealed a
      high-grade lesion (42% vs 23%, P < 0.0001), complex lesion morphology (49% vs
      20%, P < 0.0001) and thrombus-containing lesions (7% vs 1%, P = 0.006) as typical
      findings in patients with unstable angina. A high-grade lesion and/or complex
      lesion (including thrombotic lesions but excluding total occlusion) was found in
      61% of unstable and 34% of stable patients (P < 0.0001). Clinical features
      including the Braunwald classification of unstable angina were then evaluated by
      means of a multivariate approach with regard to their ability to predict the
      presence of unstable coronary artery lesions. Multivariate analysis revealed an
      abnormal ECG as the single most predictive clinical indicator of complex lesion
      morphology (P < 0.0001, odds ratio 4,2). The clinical presentation of recent
      onset of angina was highly predictive of a high grade lesion (P = 0.0003, odds
      ratio 3,2). The endpoint of a high-grade and/or a complex lesion was identified
      by an abnormal ECG (P = 0.0015, odds ratio 3,0) and recent onset angina (P =
      0.0119, odds ratio 2,5). Thus, a high grade and/or complex lesion, typical of
      patients with unstable angina, was best identified by the clinical feature of
      recent onset angina and/or abnormal ECG changes.

PMID- 8881845
TI  - Felodipine in addition to beta-adrenergic blockade for angina pectoris. a
      multicentre, randomized, placebo-controlled trial.
AB  - The additional efficacy, duration of action and tolerability of felodipine were
      evaluated in patients with stable angina pectoris and a positive stress test who
      were already receiving therapy with a beta-adrenergic blocker. One hundred and
      twenty-eight patients were randomized to double-blind treatment with 5-10 mg
      felodipine once daily or matching placebo, and were evaluated by serial exercise
      testing during 12 weeks of treatment. Felodipine at 4 h significantly increased
      exercise duration assessed after 4 weeks of treatment (increase 34 +/- 65 s vs 18
      +/- 71 s in placebo-treated patients; 95% confidence interval 1.01-1.11; P =
      0.01), and after 12 weeks of treatment (increase 39 +/- 103 s vs 3 +/- 72 s; 95%
      confidence interval 1.01-1.16; P = 0.02). The time until onset of exercise
      induced anginal pain and time until 1 mm ST depression assessed after 4 weeks of
      treatment also increased significantly with felodipine compared to placebo. No
      statistically significant changes in exercise test parameters evaluated 24 h
      after medication were observed. The addition of felodipine once daily
      demonstrated a sustained improvement in exercise duration in patients symptomatic
      despite treatment with a beta-blocker evaluated 4 h after drug intake. At 24 h
      post dose, no statistically significant effect was observed. Felodipine is well
      tolerated with a low incidence of side-effects and no adverse effect on quality
      of life.

PMID- 8881846
TI  - ST segment depression in lateral limb leads in inferior wall acute myocardial
      infarction. Implications regarding the culprit artery and the site of
      obstruction.
AB  - We examined whether the pattern of ST segment depression in lateral leads (I,
      aVL, V5, V6) in the initial electrocardiogram of patients (n = 88) with inferior
      wall acute myocardial infarction (ST segment elevation of > or = mm in > or = 2
      inferior leads) correlates with the site of obstruction, as determined
      angiographically during acute hospitalization. Of the 62 patients in which the
      culprit artery could be determined unequivocally, in 46 the culprit artery was
      the right coronary artery (20 proximal to the first right ventricular branch and
      26 distal), and in 16 the left circumflex coronary artery (seven proximal to the
      first marginal branch or involving a high first marginal branch, and nine with
      distal obstruction). Significant ST segment depression (ST < or = 1 mm) in leads
      I and aVL was more common in right coronary artery obstruction (P < 0.05 and P <
      0.0001, respectively). The absence of significant ST segment depression in lead
      aVL was most common in proximal circumflex obstruction (P < 0.0001), with a
      similar trend for lead I (P < 0.11). ST segment depression patterns in leads V5
      and V6 were not indicative of the infarct-related artery or the site of
      obstruction. Thus, significant ST segment depression in leads I and aVL indicates
      right coronary artery-associated inferior wall acute myocardial infarction with a
      sensitivity of 70% and 100%, and a specificity of 63% and 38%, respectively,
      whereas the lack of ST segment depression in these leads indicates proximal
      circumflex obstruction with a sensitivity of 71% and 86%, and a specificity of
      65% and 100%, respectively.

PMID- 8881847
TI  - Clinical validation of a quality of life questionnaire in angina pectoris
      patients.
AB  - Angina pectoris impairs patients' quality of life. In order to assess its impact
      on quality of life, a questionnaire was developed using a literature review and
      interviews with patients and clinicians. It consisted of a general profile (SF
      36) which measured functional status, well-being, perceived health, and a
      specific index, the Angina Pectoris Quality of Life Questionnaire, supplemented
      by new items. The acceptability, internal consistency reliability and clinical
      validity of this 70-item questionnaire were analysed in a cross-sectional study.
      Of 197 coronary patients approached, 93% (n = 184) agreed to participate and 86%
      (n = 170) returned the mailed questionnaire. Mean age of patients was 67 years
      (+/- 10); 79% were male and 70% were retired. Sixty patients were asymptomatic
      and 110 reported anginal crises (Canadian Cardiovascular Society Classification:
      class I: 48; II: 37; III: 13; IV: 0; V: 12). Globally, angina pectoris was found
      to affect each quality of life concept measured: physical functioning, well
      being, and perceived health. Quality of life profiles worsened in accordance with
      increasing severity of the condition, as stratified by angina pectoris class.
      Asymptomatic patients reported better general and specific profiles. These
      results support the feasibility and usefulness of evaluating quality of life
      using the questionnaire. The validation of the data is very encouraging and
      enables the questionnaire to be used in clinical trials.

PMID- 8881848
TI  - Comparison of Nottingham Health Profile (NHP) scores with exercise duration and
      measures of ischaemia during treadmill exercise testing in patients with coronary
      artery disease.
AB  - A cross-sectional study of patients with stable coronary artery disease was
      performed to compare perceived health status with the results of a treadmill
      exercise test. One hundred and twenty one patients, mean age 55.07 years, 106
      male, who had all suffered a myocardial infarction under the age of 56 years, up
      to 9 years earlier were studied. Perceived health status was assessed using the
      Nottingham Health Profile, part 1 of which assesses six dimensions of normal
      living, and part 2 seven areas of daily life. Nottingham Health Profile scores
      were higher (worse perceived health status) in patients with poor treadmill
      exercise capacity within all dimensions of part 1 (energy, pain, physical
      mobility P < 0.001, emotional reactions, sleep P < 0.01, social isolation P <
      0.05) and most of those within part 2 (care of home, taking holidays P < 0.001,
      hobbies P < 0.01, relationships at home, sex life P < 0.05). The perceived health
      status of patients without a history of angina is significantly better than those
      with angina (pain, physical mobility P < 0.001, energy, emotional reactions,
      social isolation P < 0.01, sleep P < 0.05, within part 1, taking holidays P <
      0.01, care of the home, social life, sex life, hobbies P < 0.05, within part 2).
      Thus, patients with a poor perceived health status, also have poorer results
      using more conventional clinical measures of coronary artery disease. The
      Nottingham Health Profile may be a useful adjunct in patient assessment.

PMID- 8881849
TI  - Acute effect of oestrogen replacement therapy on treadmill performance in
      postmenopausal women with coronary artery disease.
AB  - The significant reduction in cardiovascular morbidity and mortality following
      oestrogen replacement therapy in postmenopausal women is only partly explained by
      an improved lipid profile. Given acutely, oestradiol causes vasodilatation and
      increases coronary blood flow and, in large doses, improves treadmill performance
      in postmenopausal women with coronary artery disease. However, the significance
      of oestrogen-mediated vasodilatation is unknown since the acute effects of
      oestradiol in doses and preparations commonly used clinically have not been
      tested. The aim of this study was to evaluate the acute effects of conventional
      replacement therapy with 17 beta-oestradiol on treadmill performance in 16
      postmenopausal women with angina in a randomized, double-blind, placebo
      controlled cross-over trial. Following baseline treadmill testing a transdermal
      oestrogen patch releasing 50 micrograms oestradiol. 24 h-1 or matching placebo
      was applied and the exercise test repeated 24 h later. The patch was then
      removed. Seven to 14 days later the sequence was repeated using the alternative
      patch. The changes in time to angina, time to 1 mm ST segment depression and
      total exercise time for each treatment compared with the corresponding baseline
      test were calculated. Plasma 17 beta-oestradiol increased with active therapy
      from 56 +/- 30 pmol.l-1 to 204 +/- 90 pmol.l-1, indicating adequate replacement.
      Compared with their respective baseline exercise tests there were no differences
      between active and placebo patches for time to angina (active: 13 +/- 55 s vs
      placebo: 10 +/- 47 s), time to 1 mm ST segment depression (active: -30 +/- 52 s
      vs placebo: 24 +/- 71 s) or total exercise time (active: 14 +/- 45 s vs placebo:
      13 +/- 35 s). Despite the recognized acute vasodilator action of larger doses of
      oestrogen, doses conventionally used in hormone replacement therapy had no acute
      effect on treadmill performance in this group of postmenopausal women with
      coronary artery disease.

PMID- 8881850
TI  - Mechanisms of angina pectoris in syndrome X assessed by myocardial perfusion
      dynamics and heart rate variability.
AB  - The fundamental abnormality in syndrome X (angina pectoris, ischaemia-like stress
      ECG despite angiographically normal coronary arteries) might be patchily
      distributed increased tone in pre-arteriolar coronary vessels with compensatory
      release of adenosine. The aim of this study was to confirm this hypothesis and to
      explore its relationships with autonomic system functioning. Using parametric
      positron emission tomography, myocardial perfusion was examined in 480 segments
      in 16 syndrome X patients and 16 age- and sex-matched healthy volunteers.
      Autonomic function was explored by Holter monitoring of time domain parameters of
      heart rate variability. Compared to volunteers, both mean perfusion (123 +/- 35
      vs 87 +/- 16 mg.min-1.100 g-1; P < 0.01) and its coefficient of variation (17.0
      +/- 3.2 vs 13.6 +/- 2.2%; P < 0.01) as a measure of perfusion heterogeneity, were
      higher in patients with syndrome X. In contrast to the findings in the control
      subjects, patients showed an inverse relationship between perfusion heterogeneity
      (coefficient of variation of segmental perfusion) and autonomic tone (heart rate
      variability parameters). Since marked perfusion heterogeneity (inversely related
      to autonomic tone) and higher overall perfusion were found, the study supports
      the data that in syndrome X hyperreactivity of small coronary vessels with
      compensatory release of adenosine may be patchily distributed.

PMID- 8881851
TI  - Requirements for quality assessment in coronary angiograph and angioplasty.
AB  - The application of formal methods of quality assessment in medicine is a
      relatively new activity. Interventional cardiology is expected to be one of the
      fields of clinical medicine adopting formal schemes of quality assessment at a
      relatively early phase because of its invasive nature, the associated risks, the
      rapid growth of this treatment and the correspondingly increasing total cost. We
      therefore aim to compile the requirements for the development of quality
      assessment schemes in angioplasty and coronary angiography. The rather disparate
      nature of methodologies applied in previous and present quality initiatives is
      reviewed, grouping the numerous methods of organizing quality initiatives found
      in the literature into a few generic schemes. This new classification of methods
      is provided as a prerequisite for the discussion of general problems inherent in
      current quality initiatives in the medical field and for the selection of
      approaches to quality development best suited for the environment of the
      catheterization laboratory. Here we identify the concrete steps of goal
      definition, quality indicator selection, definition of standards and thresholds
      for these indicators and the selection of a quality management scheme for
      monitoring the aspects of quality previously defined. Because of the limitations
      of each of the original methodologies of quality assessment, we propose a
      synthesis of the most important approaches as the basis for new quality
      initiatives in interventional cardiology.

PMID- 8881852
TI  - Simplified method for compression of femoral false aneurysms.
AB  - False aneurysm formation is a not uncommon complication of cardiac
      catheterization. Until recently, surgical repair was the only therapeutic option
      available when conservative management failed. However, Doppler-guided
      compression of the aneurysm has been advocated in recent years; the method
      requires prolonged indirect manual compression of the femoral artery aneurysm and
      is uncomfortable for both the patient and operator. In ten consecutive patients
      the use of Doppler-guided clamp placement and aneurysm compression for 60 min
      resulted in complete thrombosis of the aneurysm in eight, and only one patient
      required surgical repair. The procedure was well tolerated by all patients
      (analgesia was administered liberally). Eight patients were discharged within 24
      h, one after 2 days and the single surgical patient remained an inpatient for 6
      days. Doppler-guided clamp compression of false aneurysms is a safe, effective
      and cost effective method of managing these patients.

PMID- 8881853
TI  - Predictors of angiographic findings when chest pain recurs after successful
      coronary angioplasty.
AB  - The angiographic findings of 569 patients who underwent repeat coronary
      angiography for recurrence of chest pain after successful coronary angioplasty
      were evaluated. On the basis of angiographic findings, 250 patients (44%) were
      classified as having restenosis, 72 (13%) incomplete revascularization, 115 (20%)
      new significant coronary artery lesions, and 132 (23%) no significant disease.
      The number of diseased vessels at the time of coronary angioplasty (P < 0.001),
      number of vessels dilated (P < 0.001), and in particular, the time from
      angioplasty to recurrent chest pain (P < 0.001), were predictive of angiographic
      findings. When chest pain recurred within 4 weeks of angioplasty, 70% of patients
      had either incomplete revascularization or no significant coronary artery
      stenosis, when it recurred between 4 and 24 weeks of angioplasty, restenosis was
      the most common finding (71%), and when it recurred more than 24 weeks after
      angioplasty, new disease was the most common finding, occurring in 53% of
      patients. Of the 115 patients who developed new disease, angioplasty was
      initially performed on 133 vessels, and 222 vessels were not dilated. At repeat
      angiography, 81 of the 133 vessels (61%) that had had angioplasty and 109 of the
      222 vessels (49%) that had not had angioplasty had new lesions; this difference
      was significant at P = 0.03. In conclusion, although the most common cause of
      recurrence of chest pain after initially successful coronary angioplasty was
      restenosis, other mechanisms may also be responsible. The time from coronary
      angioplasty to onset of recurrent chest pain was the most powerful predictor of
      angiographic outcome. The incidence of new lesion development was higher in the
      vessels that had instrumented angioplasty, possibly reflecting accelerated
      atherosclerosis or increased fibrocellular proliferation from intimal injury.

PMID- 8881854
TI  - Mechanisms of luminal enlargement and quantification of vessel wall trauma
      following balloon coronary angioplasty and directional atherectomy.
AB  - OBJECTIVES: The purpose of this study was to assess the dual action of lumen
      enlargement and vessel wall damage following either balloon angioplasty or
      directional atherectomy, using intracoronary ultrasound, and angioscopy.
      BACKGROUND: Differences in the mechanisms of action of balloon angioplasty and
      directional atherectomy may have a significant bearing on the immediate outcome
      and the restenosis rate at 6 months. METHODS: A total of 36 patients were studied
      before and after either balloon angioplasty (n = 18) or directional atherectomy
      (n = 18). Ultrasound measurements included changes in lumen area, external
      elastic membrane area and plaque burden. In addition, the presence and extent of
      dissections were assessed to derive a damage score. Angioscopic assessment of the
      dilated or atherectomized stenotic lesions was translated into semi-quantitative
      dissection, thrombus and haemorrhage scores. RESULTS: Atherectomy patients had a
      larger angiographic vessel size compared with the angioplasty group (3.55 +/-
      0.46 mm vs 3.00 +/- 0.64 mm, P < 0.05); however, minimal lumen diameter (1.18 +/-
      0.96 mm vs 0.85 +/- 0.49 mm) and plaque burden (17.04 +/- 3.69 vs 15.23 +/- 4.92
      mm2) measurements did not differ significantly. As a result of plaque reduction,
      atherectomy produced a larger increase in luminal area than the angioplasty group
      (5.80 +/- 1.78 mm2 vs 2.44 +/- 1.36 mm2, P < 0.0001). Lumen increase after
      angioplasty was the result of 'plaque compression' (50%) and wall stretching
      (50%). Additionally, in both groups there was indirect angioscopic evidence of
      thrombus 'microembolization' as an adjunctive mechanism of lumen enlargement.
      Angioscopy identified big flaps in six and small intimal flaps in 11 of the
      atherectomized patients as compared with five and 12 patients in the angioplasty
      group. Changes in thrombus score following both coronary interventions were
      identical (0.72 +/- 3.42 points atherectomy vs -0.38 +/- 3.27 points balloon
      angioplasty, ns). CONCLUSIONS: Lumen enlargement after directional atherectomy is
      mainly achieved by plaque removal (87%), whereas balloon dilation is the result
      of vessel wall stretching (50%) and plaque reduction (50%). Despite the fact that
      the luminal gain achieved by directional atherectomy is twice that achieved with
      balloon angioplasty, the extent of trauma induced by both techniques seems to be
      similar.

PMID- 8881855
TI  - The importance of abnormalities of liver function tests in predicting mortality
      in chronic heart failure.
AB  - A number of simple clinical and laboratory variables were analysed in a group of
      patients with chronic heart failure to evaluate their prognostic significance.
      Five hundred and fifty-two patients were followed for a maximum of 13 years with
      a total exposure time to death or censored survival of 1148 years. Of the
      clinical variables, diuretic dose and NYHA class were related to mortality (P <
      0.01), and ischaemic heart disease was associated with a worse prognosis than
      other aetiologies (P < 0.05). Of the laboratory variables, abnormalities of liver
      function tests including bilirubin (P < 0.01), aspartate transaminase (P <
      0.005), gamma glutamyl transpeptidase (P < 0.005) and alkaline phosphatase (P <
      0.01) were all related to mortality as was plasma urate (P < 0.01). Multivariate
      survival analysis of all variables showed aspartate transaminase (chi 2 17.36, P
      < 0.001) accounted for the greatest variance followed by serum bilirubin (chi 2
      14.35, P < 0.005). Thus, abnormalities in liver function tests have prognostic
      importance in chronic heart failure.

PMID- 8881856
TI  - Right ventricular dysplasia as a generalized cardiomyopathy? findings on magnetic
      resonance imaging.
AB  - The aim of our study was to define cardiac morphological and functional
      abnormalities of right ventricular dysplasia by magnetic resonance imaging.
      Twenty-two healthy volunteers (age, 37.7 +/- 14.2 years) free of cardiac or
      respiratory diseases (group I) and 12 patients (age, 41.9 +/- 15.8 years) with
      clinical, electrophysiological and cineangiographic diagnosis of right
      ventricular dysplasia (group II) underwent magnetic resonance imaging at 0.2
      Tesla. End-diastolic diameter, trabecular disarray and segmental wall motion
      abnormalities were evaluated for the right ventricle as were adipose replacement
      and fractional shortening for both ventricles. The right ventricular end
      diastolic diameter was significantly enlarged in group II (P = 0.0023). Right
      ventricular trabecular disarray was mild in two group I subjects, and moderate in
      seven and massive in five group II patients. Right ventricular systolic bulges
      were found in seven group II patients, aneurysms in five. Excellent agreement was
      found between magnetic resonance imaging and cineangiography for bulges,
      aneurysms and tricuspid regurgitation (P < 0.0001). On spin-echo images, signal
      hyperintensities, due to adipose replacement, were found in 44 cardiac regions in
      group II: right ventricular outflow tract (12), sub-tricuspid posterobasal region
      (8), right ventricular apex (9), right ventricular anterior wall (6),
      interventricular septum (4), left ventricular lateral wall (4), left ventricular
      apex (1). Significant signal-to-noise ratio differences were found between group
      II abnormal areas and group I myocardial tissue for the right (P < 0.0001) and
      left ventricles (P = 0.0006). Fractional shortening in the right and left
      ventricles were significantly reduced in group II (P = 0.0002 and P = 0.00016,
      respectively). Magnetic resonance imaging can be considered a very useful
      diagnostic tool for the detection of features typical of right ventricular
      dysplesia, such as adipose replacement, trabecular disarray, bulges and aneurysms
      and provides useful information about cardiac function and regional wall motion.
      It indicates that left ventricular involvement occurs in a significant fraction
      of patients, and suggests that right ventricular dysplasia may be a generalized
      cardiomyopathy.

PMID- 8881857
TI  - Long-term efficacy of d/l sotalol in patients with sustained ventricular
      tachycardia refractory to class I antiarrhythmic drugs.
AB  - The efficacy of d/l sotalol was investigated in 50 patients (43 men, seven women;
      33 with coronary artery disease, 15 with dilated cardiomyopathy; ejection
      fraction 33 +/- 10%) with inducible sustained ventricular tachycardia. Before d/l
      sotalol a mean of 2 +/- 1 (1 to 4) class I antiarrhythmic drugs were ineffective.
      In 24 patients (48%) oral d/l sotalol (320 +/- 47 mg.day-1) prevented induction
      of the ventricular tachycardia; in 23 patients the ventricular tachycardia
      remained inducible (d/l sotalol 326 +/- 50 mg.day-1). The electrophysiological
      effects of d/l sotalol did not differ between patients in whom d/l sotalol
      prevented induction of ventricular tachycardia and those in whom the ventricular
      tachycardia remained inducible. In two patients, torsade des pointes developed
      after oral application of d/l sotalol; one patient suffered from severe
      hypotension even with 80 mg of sotalol per day. During long-term follow-up (27 +/
      12 months) 5/24 patients (21%) had a non-fatal recurrence of ventricular
      tachycardia (1 week to 21 months), one patient died suddenly and another from
      progressive heart failure. In patients in whom the ventricular tachycardia could
      be induced despite oral application of d/l sotalol, control of the ventricular
      tachyarrhythmia was attempted by the use of sotalol in combination with
      mexiletine (n = 2), amiodarone (n = 9), catheter ablation (n = 2),
      antitachycardia surgery (n = 1) or the implantation of an automatic cardioverter
      defibrillator (n = 12). Recurrence of ventricular tachycardia was observed in
      four patients without an implanted cardioverter defibrillator. Seven out of 12
      patients with an implanted cardioverter defibrillator received appropriate shocks
      or successful antitachycardia pacing. Although no patient died suddenly, overall
      mortality was 17% in this group. It is concluded that d/l sotalol is highly
      effective in the suppression of sustained monomorphic ventricular tachycardia
      inducible by programmed electrical stimulation. However during a mean follow-up
      of 27 +/- 12 months a recurrence of ventricular tachycardia was seen in 21% of
      patients, and one patient died suddenly.

PMID- 8881858
TI  - Evaluation of atrial vulnerability with transoesophageal stimulation in patients
      with atrioventricular junctional reentrant tachycardia. Comparison with patients
      with ventricular pre-excitation and with normal subjects.
AB  - The aim of our work was to evaluate the inducibility of atrial fibrillation in a
      group of patients with atrioventricular junctional reentrant tachycardia and to
      compare it with that of patients with a Kent-type ventricular pre-excitation
      (Wolff-Parkinson-White syndrome) and a control group. One hundred and twenty-five
      subjects were separated into groups. Group 1 comprised 49 Wolff-Parkinson-White
      patients, with a mean age of 26.4, range 10-66 years; group 2, 51 patients with
      atrioventricular junctional reentrant tachycardia inducible by transoesophageal
      atrial stimulation and/or clinically documented, with a mean age of 43.4, range
      16-78 years; group 3, 25 control subjects with a mean age of 26.4, range 13-76
      years. Each subject underwent atrial transoesophageal stimulation with the
      following protocol: programmed atrial stimulation with 1 and 2 stimuli during
      atrial pacing of 100.min-1 and 150.min-1; atrial stimulation for 10 s at a rate
      of 200-300-400-500-600.min-1 with intervals of 10 s between stimulations, five
      successive 'ramp-up' atrial stimulations for 9 s with the rate increasing from
      100 to 800.min-1 with intervals of 10 s between stimulations. The end point was
      the completion of the protocol or induction of sustained atrial fibrillation (> 1
      min). The chi-square test was used for statistical analysis. Our results showed
      that in group 1 atrial fibrillation was induced in 27/49 patients (55.1%); this
      was sustained in 13/49 (26.5%) and non-sustained in 14/49 (28.5%); in group 2,
      atrial fibrillation was induced in 22/51 patients (43.0%); it was sustained in
      7/51 (13.7%) and non-sustained in 15/51 (29.4%); in group 3, sustained atrial
      fibrillation was not induced in any subject and in only one subject was a non
      sustained atrial fibrillation (4 s) induced. The chi-square test showed that
      group 2 vs group 1 were non-significant, while group 2 vs group 3 and group 1 vs
      group 3 were significant (P < 0.003 and P < 0.0007, respectively). Therefore
      group 2 patients showed a greater atrial vulnerability in comparison to the
      control subjects and a similar vulnerability to group 1 patients. It is possible
      that the greater atrial vulnerability in the patients of group 2 was due to the
      double nodal pathway.

PMID- 8881859
TI  - Heart rate variability and inappropriate sinus tachycardia after catheter
      ablation of supraventricular tachycardia.
AB  - Sinus tachycardia has been reported after radiofrequency catheter ablation of
      supraventricular tachycardia. Frequently, these patients require beta-blocking
      agents for symptomatic control. The purpose of this study was to evaluate
      prospectively the incidence of inappropriate sinus tachycardia and heart rate
      variability after ablation of atrioventricular nodal reentrant tachycardia and
      accessory pathways. Patients undergoing ablation had 24-h ambulatory monitoring
      ECG (Holter) performed before the procedure, on the day of the ablation, and 3
      months afterwards. There were 170 patients, mean age 48 +/- 23 years; 93 were
      female. A complete study of the 24-h Holter with analysis of heart rate
      variability: SD, rMSSD, pNN50, high and low frequency was obtained. There was a
      low prevalence of inappropriate sinus tachycardia after the ablation procedure
      (10 of 170 patients: five with four atrioventricular nodal reentry, with
      posteroseptal accessory pathways and one of the latter following ablation of the
      left accessory pathway). There was no modification of time and frequency domain
      parameters of heart rate variability in the remaining patients who underwent
      radiofrequency ablation. Holter monitoring 3 months after ablation showed that
      parameters of heart rate and heart rate variability had normalized in patients
      who had developed inappropriate sinus tachycardia. Inappropriate sinus
      tachycardia may be initiated by both radiofrequency ablation of atrioventricular
      nodal reentrant tachycardia and radiofrequency ablation of posteroseptal
      accessory pathways. Specific damage to the posteroseptal region is responsible
      for these changes, which usually recover spontaneously after 3 months.

PMID- 8881860
TI  - Effects of the new class III antiarrhythmic drug dofetilide on the atrial and
      ventricular intracardiac monophasic action potential in patients with angina
      pectoris.
AB  - The class III antiarrhythmic drug dofetilide is known to prolong action potential
      duration by specific blockade of the delayed rectifier potassium channel Ik. As
      dofetilide is likely to be used in the treatment of atrial arrhythmias it is
      important to determine the relative sensitivity of the atrium and ventricle in
      man. Twelve male patients underwent monophasic action potential and refractory
      period recordings from the high right atrium and right ventricular septum. The
      patients received either 8 micrograms.kg-1 dofetilide or placebo intravenously.
      The mean QTc was prolonged by 11% (SD 5%, P < 0.00001) in the active group; the
      mean monophasic action potential increased by 31% (SD 15%, P < 0.0005) in the
      atrium and 27% (SD 9%, P < 0.00005) in the ventricle; the mean effective
      refractory period increased by 30% (SD 16%, P < 0.0005) in the atrium and 20% (SD
      6%, P < 0.0001) in the ventricle. No significant change occurred in the placebo
      group. There was no significant difference in effect between the two chambers.
      The change in QTc did not accurately reflect acute changes in refractory period
      or monophasic action potential duration. This has important implications for the
      use of QT prolongation to assess the acute effect of class III drugs.

PMID- 8881861
TI  - A comparison of non-invasive continuous finger blood pressure measurement
      (Finapres) with intra-arterial pressure during prolonged head-up tilt.
AB  - Simultaneous intra-radial and non-invasive (Finapres, Ohmeda) blood pressures
      were compared during prolonged head-up tilt, in eight patients (mean age 49
      years) with malignant vasovagal syncope. Twelve tilts were performed, of which
      eight resulted in vasovagal syncope. The mean bias (difference between Finapres
      and intra-arterial pressures) for systolic pressure was +0.7 mmHg (standard
      deviation 11.3 mmHg) and for diastolic pressure was +5.4 mmHg (standard deviation
      7 mmHg). The within-tilt precision (standard deviation of the bias) of the non
      invasive measurements varied between 2.9-12.4 mmHg (median 4.5 mmHg) for systolic
      comparisons, and 1.6-8.4 mmHg (median 4.4 mmHg) for diastolic comparisons. In all
      but one tilt highly significant positive increases in both systolic (median 7.1
      mmHg) and diastolic bias (median 8.1 mmHg) occurred on tilt with respect to
      resting pre-tilt levels. Independent of the absolute level of agreement, the non
      invasive measurements followed changes in intra-arterial pressure closely, with
      89% of beat-to-beat changes in systolic pressure, and 95% of beat-to-beat changes
      in diastolic pressure followed to within +/- 2 mmHg. This study suggests that the
      Finapres is well suited for use during diagnostic tilt testing, demonstrating an
      acceptable within-tilt precision and closely following pressure changes during
      vasovagal syncope.

PMID- 8881862
TI  - Age-related changes in structure and relative collagen content of the human and
      feline sinoatrial node. A comparative study.
AB  - Age-related changes in the structure and size of the human and cat sinoatrial
      nodes were studied by light microscopy, with emphasis on changes in relative
      collagen volume. Sinoatrial nodes from 41 humans (aged 0-94 years) and 21 cats
      (aged 6 weeks-18 years) were used. It was found that there were no changes in the
      dimensions of the sinoatrial node during adult life in either species. In Sirius
      Red F3 Ba stained sections, the relative volume of collagen was measured using an
      interactive image analysis system. The relative volume of collagen in the human
      sinoatrial node increases from 38% during childhood to 70% during adulthood. Once
      adulthood is reached, there are no further changes in the relative volume of
      collagen. In the cat sinoatrial node the relative volume of collagen is only 27%
      and does not change with age. The organisation of collagen in the sinoatrial
      node, however, demonstrates an age-dependent change in both humans and cats. From
      coarse strands between clusters of nodal cells it gradually changes into a fine
      network of isolated collagen fibres which surround individual nodal cells. This
      process is more pronounced in humans. It is concluded that age-related changes in
      sinoatrial node function are not related to an increase in collagen content in
      the sinoatrial node.

PMID- 8881863
TI  - Review of the long-term course of 52 patients with pulmonary atresia and
      ventricular septal defect. Anatomical and surgical considerations.
AB  - This study reviews the long-term course of 52 patients with pulmonary atresia and
      ventricular septal defect seen in a single institution and followed for a mean
      period of 8.6 years (range 2 days to 20 years). Before the first operation,
      pulmonary blood supply was provided by ductus arteriosus supplying confluent
      pulmonary arteries in 26 patients (50%, group I), and was partially or entirely
      dependent on systemic collateral arteries in the other 26 patients (group II).
      The angiographic mean ratio of diameters of the right and left pulmonary
      artery/descending aorta (McGoon ratio) was significantly lower in group II than
      in group I, 0.76 +/- 0.42 vs 1.04 +/- 0.17 (P = 0.006). Severe arborization
      defects (with fewer than 10 pulmonary vascular segments connected to central
      pulmonary arteries) were present only in group II patients (eight patients: 15%),
      six of whom had congenital absence of the central pulmonary arteries. Corrective
      surgery was performed in 23 patients (44%, 14 in group I, nine in group II). All
      but one, who died later, had a McGoon ratio > or = 1 (mean 1.19 +/- 0.18) at time
      of repair. There was one hospital death (4%) and two late deaths (9%). All but
      one of the surviving corrected patients were in functional class I or II. Conduit
      replacement reoperation was performed in three patients (14%), 6, 10 and 13
      years, respectively, after repair. At the end of the study, among the 37 patients
      (71%) who were alive (17 in group I, 20 in group II), 20 (39%) were corrected (12
      in group I, eight in group II), four await corrective surgery, and six (11.5%)
      are estimated inoperable (all in group II) because of very hypoplastic or absent
      pulmonary arteries. This study confirms the estimated rate in the published
      literature of long-term survival in patients with pulmonary atresia and
      ventricular septal defect, and the good results of corrective surgery whenever
      the size and distribution of pulmonary arteries are satisfactory. The problem of
      very hypoplastic pulmonary arteries and severe arborization defects remains
      contentious.

PMID- 8881864
TI  - Magnetic resonance imaging of the pulmonary venous flow pattern in mitral
      regurgitation. Independence of the investigated vein.
AB  - OBJECTIVES: The aim of the present study was two-fold: first, to quantify
      characteristic parameters of the pulmonary venous flow pattern in patients with
      mitral regurgitation by using magnetic resonance phase velocity mapping; second,
      to determine whether this pattern is dependent on the vein being investigated and
      the direction of the regurgitant jet. BACKGROUND: Echocardiographic findings
      threw doubt on whether the pulmonary venous flow pattern is independent of the
      vein being investigated and whether the flow velocities in the pulmonary veins
      have a linear relationship with the volume flow. SUBJECTS AND METHODS: Flow
      patterns were assessed in all four pulmonary veins by magnetic resonance velocity
      mapping in healthy volunteers and in 17 patients with echocardiographically mild
      and 13 patients with severe regurgitation. RESULTS: No differences were found
      between the use of velocity or volume flow for characterizing individual curves.
      The pulmonary venous flow pattern in controls was characterized by six points, a
      biphasic systolic wave (maximum systolic volume flow: 29 +/- 18 ml.s-1), and end
      systolic descent (24 +/- 18 ml.s-1), a biphasic diastolic wave (maximum diastolic
      volume flow: 69 +/- 22 ml.s-1) and an end-diastolic reversed flow. Reversed end
      systolic flow was a characteristic sign of severe regurgitation (-10 +/- 18 ml.s
      1). The systolic-to-diastolic flow ratio was lower in severe regurgitation (0.5
      +/- 0.6) than in mild regurgitation (1.4 +/- 0.9), P < 0.0001). In severe
      regurgitation, the normalized time intervals from Q wave to the highest systolic
      peak and end-systolic descent were of less prolonged duration than in mild
      regurgitation and controls (P < 0.01). Flow patterns between veins were similar
      and the median of the correlation coefficients between the curves was the same in
      patients with or without an eccentric jet, 0.80 and 0.81, respectively.
      CONCLUSION: Magnetic resonance velocity mapping is helpful in determining and
      understanding pulmonary venous flow characteristics. It is demonstrated that the
      pulmonary venous flow pattern is independent of the vein being investigated
      irrespective of the regurgitant jet direction, and that it is useful in grading
      mitral regurgitation.

PMID- 8881865
TI  - Is the clinical spectrum and prognosis of native valve infective endocarditis in
      non-addicts changing?
AB  - One hundred and ninety-four episodes of endocarditis on native valves in non
      addict patients were diagnosed from 1975 to 1992 and were divided into groups A
      (78 patients, 1975-1983) and B (116 patients 1984-1992). Both groups had the same
      gender distribution, similar valvular involvement and microbiological
      characteristics. In group B patients, median age was older (46 vs 54 years, P =
      0.0002), the number of patients without previous heart disease was higher (46% vs
      22%, P = 0.02) and the median time of symptoms before diagnosis was shorter (30
      vs 50 days, P = 0.038). Both groups had similar incidence of heart failure (32%
      vs 36%), surgical treatment (30% vs 33%) and embolic episodes (26% vs 34%).
      Surgical mortality decreased from 43% to 18% (P = 0.03). Overall mortality
      decreased non-significantly from 19% in group A to 12% in group B. Predictors of
      death in group A were heart failure (odds ratio 9.6, 95% confidence interval 3
      36) and surgical treatment (odds ratio 5, 95% confidence interval 1.3-19).
      Predictors of death in group B were age (odds ratio 4.98, 95% confidence interval
      1.4-19), female sex (odds ratio 5.3, 95% confidence interval 1.3-20),
      staphylococcal infection (odds ratio 4.9, 95% confidence interval 1.1-22) and
      heart failure (odds ratio 5.2, 95% confidence interval 1.3-20). Although in
      recent years infective endocarditis occurs in older patients and is more common
      in patients with previously unknown heart disease a substantial change in major
      clinical and prognostic variables is not apparent in our population. Overall in
      hospital mortality has decreased from 19% to 12% mainly due to better surgical
      results.

PMID- 8881866
TI  - Evaluation of regional haemodynamics and alterations of vascular wall of the
      lower limbs in hypertensive subjects.
AB  - This study was designed to analyse the relationship between arterial hypertension
      and changes in arterial blood flow and vascular wall damage of the lower limbs in
      hypertensive patients with various degrees of hypertension. Six hundred and fifty
      four hypertensive patients (421 males and 233 females) aged 35 to 70 years and 88
      healthy subjects (63 males and 25 females) aged 39 to 60 years were studied.
      Strain-gauge plethysmography of the lower limbs was used to calculate arterial
      calf blood flow (RF), arterial calf blood flow after post-ischaemic hyperaemia
      (PF), basal and minimal vascular resistances (BVR and MVR), time to reach peak
      flow (tPF), time until 50% reduction of peak flow (tT1/2) and total recovery time
      (tT). In 108 (67 males and 41 females) of the hypertensive patients, a
      morphological study by echo-Doppler duplex scanning of the popliteal artery was
      performed to measure medial-intimal thickening and popliteal lumen diameter. Our
      results indicate that regional haemodynamics of the lower limbs worsened in
      hypertensives in comparison with control subjects. In addition, the change in
      peripheral haemodynamics was related to the degree of hypertension. Moreover,
      medial--intimal thickening was significantly (P < 0.05) higher in severe
      hypertensives than mild hypertensives. Popliteal lumen diameter was significantly
      (P < 0.05) lower in severe hypertensives than moderate and mild hypertensives. In
      all these subjects mean blood pressure was correlated directly (r = 0.31; P <
      0.001) with medial-intimal thickening and inversely (r = -0.37; P < 0.001) with
      popliteal lumen diameter. Multiple regression analysis indicated that mean blood
      pressure, age and serum cholesterol were independently correlated to medial
      intimal thickening. This relationship was not influenced by the diabetic patients
      and smokers among the groups. Our results indicate that hypertension impairs
      peripheral flow and encourages the development of medial-intimal thickening.

PMID- 8881867
TI  - A new variant of type IV glycogenosis with primary cardiac manifestation and
      complete branching enzyme deficiency. In vivo detection by heart muscle biopsy.
AB  - Type IV glycogenosis (polyglucosan body disease) is a rare congenital autosomal
      recessive inherited disorder, caused by lack of the branching enzyme (amylo-1,4
      1,6 transglucosidase). This deficiency leads to storage of abnormal glycogen
      (polyglucosan bodies) in the liver and other tissues. The clinical onset of the
      disease is insidious with non-specific gastrointestinal symptoms followed by
      progressive hepatic failure. Usually patients die due to hepatic cirrhosis within
      4 years. Sometimes myopathy of the heart and skeletal muscle is also present. In
      these cases, the clinical onset is often later than in typical cases. We report
      on two brothers with primarily cardiac manifestation and late onset of the
      disease. The older one started to suffer from progressive dilated cardiomyopathy
      at the age of 18 years, presenting with severe heart failure, hepatosplenomegaly,
      ascites and peripheral oedema. He also demonstrated myopathy and muscular atrophy
      especially of the shoulder and lower limbs. Initially he improved on medical
      therapy, but one year later severe heart failure recurred followed shortly
      afterwards by sudden cardiac death. Right heart and skeletal muscle biopsies were
      performed while he was alive. These, as well as the autopsy, revealed massive
      accumulation of polyglucosan bodies. In both heart and skeletal muscle, complete
      branching enzyme deficiency could be proven. His 14-year-old brother showed
      similar clinical findings of mild dilated cardiomyopathy. His muscle biopsy also
      revealed polyglucosan body myopathy. Thus, in young patients presenting with
      congestive cardiomyopathy, type IV glycogenosis has to be considered in the
      differential diagnosis.

PMID- 8881868
TI  - The haemodynamic effect of prophylactic peri-operative dopexamine in coronary
      artery bypass patients.
AB  - Twenty-three low risk coronary artery bypass graft patients underwent a
      controlled study of the effects of prophylactic perioperative dopexamine
      hydrochloride on haemodynamic indices and peripheral perfusion. The infusion
      commenced following induction of anaesthesia and continued for 24 h
      postoperatively. The study demonstrated that dopexamine significantly increased
      cardiac index compared with the control group (P < 0.05) and that this effect was
      mediated through an increase in both left ventricular stroke volume index and
      heart rate (P < 0.05). This was associated with a significantly lower systemic
      vascular resistance (P < 0.05), without an increase in left ventricular stroke
      work index in the dopexamine group. Despite normal pre-operative left ventricular
      function, both groups exhibited a fall in pH (P < 0.05) relative to baseline
      levels. This fall in pH began prior to cardiopulmonary bypass and persisted in
      the early postoperative period in both groups, suggestive of tissue hypoperfusion
      and oxygen deficiency. These indices normalized more rapidly in the dopexamine
      group, suggesting a more rapid reversal of an intra-operative oxygen debt in this
      group. The study demonstrates the mechanism of action of dopexamine on cardiac
      function and peripheral perfusion during cardiac surgery and shows that the
      inodilator properties during cardiac surgery are useful haemodynamically and
      facilitate early reversal of tissue hypoperfusion and oxygen debt in this
      environment.

PMID- 8881869
TI  - Acute effects of atrial natriuretic peptide on left ventricular diastolic
      function. a pulsed wave Doppler study in man.
AB  - Doppler echocardiographic indices of diastolic function and systemic
      haemodynamics were studied in response to infusions of atrial natriuretic peptide
      (0.5, 1, 2, 5 pmol.kg-1.min-1) and placebo (0.9% (w/v) saline) in ten normal male
      subjects. Compared with placebo, atrial natriuretic peptide infusion produced a
      significant and dose-related reduction in the isovolumic relaxation time [(mean
      and 95% CI) -5.9 (-9.2 to -2.6) ms (P < 0.01) at 5 pg.kg-1 min-1] and a
      significant increase in the ratio between early and late transmitral peak
      velocities [0.46 (0.02 to 0.89) (P < 0.05) at 5 pg.kg-1 min-1]. No significant
      changes in heart rate, blood pressure or aortic stroke distance were observed
      with infusion of atrial natriuretic peptide compared with placebo. These data
      suggest that pathophysiological plasma concentrations of atrial natriuretic
      peptide improve diastolic function by increasing the rate of myocardial
      relaxation.

PMID- 8881870
TI  - The relationship of autonomic function to age-related changes in left ventricular
      filling in normal subjects.
AB  - Heart rate and age are independent variables associated with the pattern of
      normal left ventricular filling. Since heart rate variability also varies with
      age, the relationship between these and left ventricular filling in normal
      subjects was assessed. In 31 subjects (age range 21 to 71 years), power spectral
      analysis of heart rate variability was determined from 24 h Holter tapes, and
      left ventricular filling was assessed by Doppler echocardiography. Relationships
      between heart rate variability and left ventricular filling were assessed by
      univariate and multivariate regression analyses. Total, low frequency and high
      frequency power each significantly correlated with the peak filling velocity with
      atrial systole (A) (r = -0.70, P < 0.0001; r = -0.69, P < 0.0001; r = -0.54, P <
      0.01, respectively), but did not correlate with measures of early diastolic left
      ventricular filling. Although age and A were related (r = 0.46, P < 0.010), age
      was no longer a significant variable when measures of heart rate variability were
      included in the multivariate regression model for A. Thus, the variability in
      measures of early diastolic filling in normal subjects appears to be independent
      of measures of heart rate variability, whereas, A is significantly associated
      with these measures.

PMID- 8881871
TI  - Dipyridamole slows the rate of isovolumic pressure fall in patients with normal
      coronary arteries.
AB  - Dipyridamole is currently used for thallium imaging and stress echocardiography.
      The coronary and haemodynamic effects of dipyridamole are well documented while
      its effects on left ventricular relaxation remain to be determined. The aim of
      the present study was to evaluate the effects of dipyridamole on left ventricular
      relaxation rate in healthy subjects. High fidelity pressure recordings were
      obtained at fixed atrial pacing (89 +/- 2 beats.min-1) in 10 subjects with normal
      left ventricular angiography and coronary arteriograms. Left ventricular pressure
      was recorded at rest and 5 min after a 4 min infusion of dipyridamole (0.14 mg.kg
      1.min-1). Dipyridamole infusion decreased left ventricular systolic pressure (P <
      0.01) and time to left ventricular systolic pressure (P < 0.01), with no changes
      in end-diastolic pressure or peak rate of pressure rise. The peak rate of
      isovolumic pressure fall decreased (from 1957 +/- 105 to 1488 +/- 100 mmHg.s-1, P
      < 0.01) and the time constant of isovolumic relaxation increased (from 37 +/- 2
      to 44 +/- 3 ms, P < 0.02). In conclusion, our study indicates that acute
      administration of clinically relevant doses of dipyridamole displays deleterious
      effects on heart relaxation in healthy humans.

PMID- 8881872
TI  - Heterogeneity of left ventricular regional wall thickening following dobutamine
      infusion in normal human subjects.
AB  - BACKGROUND: Pathophysiological data and pragmatic clinical experience with stress
      echocardiography suggest that inotropic stimulation with simultaneous changes in
      heart rate and loading conditions can affect the function of various myocardial
      regions asymmetrically, inducing heterogeneity in wall motion and thickening,
      possibly mimicking 'ischaemic' regional hypokinesis or lack of hyperkinesis
      during stress. OBJECTIVES: To describe, in a quantitative fashion, the
      physiological contractile response of different left ventricular regions
      following dobutamine infusion. METHODS: Two hundred and twenty-three in-hospital
      patients undergoing dobutamine stress echocardiography and coronary angiography
      were initially considered. Of these 223 patients, 18 had angiographically normal
      coronary arteries, normal resting function, negative ergonovine and exercise
      stress tests, and negative dobutamine stress echocardiograms; of the 18, only in
      11 patients (six females, age = 56 +/- 10 years) was it possible to obtain
      quantitative measurements of the middle segments of the inferior, anterior,
      lateral, and septal walls. Two-dimensional echocardiographic measurements of wall
      thickness were obtained at the end-diastolic (onset of Q wave) and end-systolic
      phases, both at baseline (rest) and at the peak of the dobutamine infusion (40
      micrograms.min-1.kg-1 plus atropine). RESULTS: Dobutamine increased heart rate
      (rest = 69 +/- 9 vs dobutamine = 138 +/- 13 beats.min-1; P < 0.01), whereas
      systolic blood pressure did not change significantly (rest = 136 +/- 15 vs
      dobutamine = 150 +/- 25 mmHg, P = ns). During stress, % systolic thickening
      decreased in the inferior wall (rest = 73 +/- 24 vs dobutamine +/- 50 +/- 9%; P <
      0.01), whereas it tended to increase to a variable extent in the other regions,
      i.e. septal (rest = 46 +/- 17 vs dobutamine = 68 +/- 13%, P < 0.01), anterior
      (rest 62 +/- 19 vs dobutamine = 69 +/- 11%, P = ns), and lateral wall (rest = 48
      +/- 16 vs dobutamine = 61 +/- 18%, P = ns). The decrease in % systolic thickening
      of the inferior wall was inversely correlated with the increase in end-diastolic
      wall thickness (r = -0.75; P < 0.01), but neither with heart rate (r = 0.15; P =
      ns) nor with systolic blood pressure changes (r = 0.05; P = ns). CONCLUSIONS:
      Heterogeneity of left ventricular wall thickening can be induced or magnified by
      dobutamine infusion even in subjects without coronary artery disease, with the
      inferior wall showing a lack of hyperkinesis, up to relative hypokinesis, in
      comparison with other myocardial regions. Caution in aggressive dobutamine stress
      echocardiography reading, especially in the inferior wall, might be warranted.

PMID- 8881873
TI  - The signal-averaged ECG becomes late potential-positive at low noise levels in
      healthy subjects.
AB  - Late potentials are detected at various noise levels in clinical studies. The aim
      of this study was to quantify the effect of residual noise level on the signal
      averaged ECG. Thirty minutes of raw ECG (lead -X, +X, -Y, +Y, -Z, and +Z) from 10
      healthy volunteers were digitized and stored on optical discs. Each ECG was
      analysed by four signal averaging procedures to noise level 0.1, 0.2, 0.3, and
      0.4 microV, respectively. At each noise level, time domain analysis of the
      filtered vector (40-250 Hz) included determination of the QRS duration (QRS),
      late potential duration (LPD, duration of terminal signals below 40 microV), and
      root-mean-square voltage of the terminal 40 ms of the filtered QRS (RMS40). On
      average, the measured signal-averaged QRS duration was prolonged by 7.0 ms (range
      0.9-12.5 ms) per 0.1 microV reduction in noise level. Late potential duration
      increased by 5.9 ms (range 0.2-10.0 ms) per 0.1 microV reduction in noise level,
      and RMS40 was reduced by 9.1 microV (range 0.5-20.2 microV) per 0.1 microV
      reduction in noise level. At noise level 0.4 microV, 0.3 microV, 0.2 microV, and
      0.1 microV the number of late potential-positive subjects were 1, 2, 4, and 6,
      respectively. Late potential parameters are significantly dependent on noise
      level after signal averaging. Using conventional criteria for late potentials,
      healthy subjects become false-positive at low noise levels. Establishment of
      standards for noise level is recommended.

PMID- 8881874
TI  - Partial papillary muscle rupture complicating acute myocardial infarction.
      diagnosis by multiplane transoesophageal echocardiography.
AB  - Papillary muscle rupture is a rare but generally fatal mechanical complication of
      acute myocardial infarction. In contrast to complete papillary muscle rupture,
      echocardiographic recognition of partial papillary muscle rupture has rarely been
      reported and seems to be more challenging. We describe a patient with partial
      papillary muscle rupture that could only be diagnosed by multiplane
      transoesophageal echocardiography, whereas transthoracic echocardiography and
      single plane transesophageal echocardiography showed only posterior mitral
      leaflet prolapse.

PMID- 8881875
TI  - Single right coronary artery assessed by contrast angiography and
      transoesophageal echocardiography.
AB  - Contrast angiography is the gold standard for the assessment of the site and
      severity of coronary artery narrowing. Transoesophageal echocardiography is
      recognized as a feasible technique in assessing coronary artery anomalies. Our
      patient had arteriosclerotic narrowing in a single right coronary artery with
      poor distal opacification during contrast injection. Combining transoesophageal
      echocardiography with contrast angiography helped us in visualizing a surgically
      accessible vessel on the anterior wall of the left ventricle.

PMID- 8881876
TI  - Multiple restenosis following PTCA.

PMID- 8881877
TI  - Cardiac involvement in seat belt-related and direct sternal trauma: a prospective
      study in management implications.

PMID- 8881878
TI  - Measurement reproducibility in cardiology.

PMID- 8881879
TI  - Exercise intolerance in patients with chronic heart failure.

PMID- 8881880
TI  - Acute myocardial infarction in the young--the role of smoking.

PMID- 8881881
TI  - The contributions and limitations of hydroxyapatite coatings to implant fixation:
      A histomorphometric study of load bearing implants in dogs.
AB  - The contribution and limitation of hydroxyapatite coatings to implant fixation
      are discussed following a 5-year histomorphological study of the bony
      incorporation of macroporous stemless hemiarthroplasties in dogs. Implants
      without coating, with a pure titanium coating and with a hydroxyapatite coating
      were compared. The mean extent of direct contact between bone and hydroxyapatite
      coated implants was 66% compared with 0 to 5% in the other implants. Areas of
      resorption of the coating were seen in every case associated with direct bone
      apposition on the metal surface. When the initial fixation is stable,
      osteointegration of hydroxyapatite-coated implants is obtained consistently,
      despite design features known to preclude bone incorporation. Implant fixation
      must depend on a mechanical interlock with bone because of the resorbability and
      mechanical properties of hydroxyapatite coatings.

PMID- 8881882
TI  - Remodelling and pain after uncemented total hip replacement.
AB  - We studied 70 patients after uncemented hip replacement with the Lord prosthesis
      which has a relatively long, completely macrotextured stem. The mean follow up
      was for 9.5 years. We compared radiographs at one year after operation, at 5
      years and at the last follow up. Twenty-five patients (36%) had deep or
      circumferential pain in the thigh. Of the 44 who were most active at 5 years
      those with thigh pain had less proximal cortical loss than those without (p <
      0.05), most cortical bone formation distally and most often had incomplete
      radiolucent lines at the mid-stem level, perhaps indicating more elastic
      displacement of the bone relative to the prosthesis. The presence of radiolucent
      lines correlated with the increase in cortical width at 5 years (p < 0.01).
      Cortical remodelling continued after 5 years at all levels except at the tip (p <
      0.01). The relative elastic displacement at the interface could cause pain and
      may contribute to the pattern of bone remodelling in the femur after uncemented
      hip replacement.

PMID- 8881883
TI  - One stage revision arthroplasty of the hip for deep gram negative infection.
AB  - We describe the use of one stage revision arthroplasty of the hip for deep gram
      negative infections. We have followed up 15 patients for an average of 8 years
      following operation. Two procedures failed, one at two years due to aseptic
      loosening and another because of persistent infection. We attribute the low
      reinfection rate (1/15) to meticulous surgical technique, preoperative parenteral
      antibiotics and antibiotic loaded cement. Both failures occurred in the two
      operations performed without antibiotic loaded cement. We do not recommend the
      use of plain cement for exchange hip arthroplasty in the presence of gram
      negative infection.

PMID- 8881885
TI  - Low-energy extracorporal shock wave therapy for persistent tennis elbow.
AB  - Fifty patients who suffered from persistent tennis elbow for more than 12 months,
      and were referred for surgical treatment, were assigned at random to 2 groups of
      low-energy extracorporal shock wave therapy. Group I received a total of 3000
      impulses of 0.08 mJ/mm2; group II (controls) 30 impulses of 0.08 mJ/mm2. Follow
      up was after 3 and 12 weeks. We found no significant differences between the 2
      groups before treatment, there was but significant relief of pain and improvement
      of function in group I with good or excellent outcome in 56% at the last
      evaluation.

PMID- 8881884
TI  - [Unstable fractures of the distal radius: a new classification].
AB  - We have carried out a retrospective study of 100 fractures of the distal radius
      which were classified according to 3 principal factors, namely the amount of
      displacement (D), the involvement of the epiphysis (E), and the degree of
      metaphyseal comminution (M). Each of these 3 groups was further divided into 4
      levels of increasing instability. The fractures were assessed 3 months after
      injury. Most occurred in old patients with low grades in the DEM scale, often in
      association with osteoporosis and following a simple fall. Metaphyseal
      comminution and the degree of displacement did not correlate with the degree of
      osteoporosis. The highest grades of epiphyseal lesions occurred in young
      patients, and intact epiphyses were seen in the more osteoporotic population. The
      Kapandji technique, using 3 Kirschner wires, was used in 58 cases, mostly with
      low grades of DEM, and gave satisfactory results, but in 14% anterior carpal
      translation was noted. This may lead to anterior instability. External fixation
      was employed in 32 patients with higher grade fractures. A good anatomical result
      was usually obtained but the wrists were more stiff. In 7 of these patients
      fixation of articular fragments by wires was also needed. Reduction and
      immobilisation in a cast was undertaken in 7 cases with variable results. Double
      cortical pinning was used in 3 patients and was useful in the highest grades of
      displacement. We outline a scheme for treatment based on our classification.

PMID- 8881886
TI  - Reconstruction of the chronically insufficient anterior cruciate ligament: long
      term results of the Eriksson procedure.
AB  - Thirty-two patients (26 men and 6 women) with symptoms due to chronic
      insufficiency of the anterior cruciate ligament were treated by reconstruction
      using the medial one-third of the patellar tendon. The average delay between
      injury and operation was 4.8 years. Prior to this, 28 operations had been carried
      out on the knees of 20 of the patients. At follow up, at an average of 6.6 years
      after reconstruction, 50% were satisfied subjectively with the end result, and
      57% were excellent or good on the Lysholm score. The Lachman test showed that 50%
      were completely stable and none had severe laxity. The anterior drawer test was
      negative in 59% and only one had moderate laxity. The pivot shift was negative in
      69% and only 2 were 2+ positive. Twenty-one of the 29 patients who were active in
      sport before their injury were able to continue their activity at the same or a
      reduced level.

PMID- 8881887
TI  - Intervertebral discitis in children: a review of 12 cases.
AB  - Twelve children with lumbar discitis were reviewed. The average age at diagnosis
      was 2.5 years. Seven were girls, and the follow-up varied between 2 and 10 years
      (average 5 years). The clinical signs were general irritability, abdominal or hip
      pain and refusal to walk or to sit. The erythrosedimentation rate was elevated in
      all but two. Radiographic narrowing of the disc space was seen in seven patients.
      Needle disc aspiration was done in five cases with two being positive for
      Staphylococcus aureus. Blood culture was positive in one case. Magnetic resonance
      imaging helped to diagnose the condition in three. Treatment consisted of bed
      rest and immobilisation of the spine; intravenous antibiotics were given to nine
      children. The natural course of the disease was benign in all our twelve cases.

PMID- 8881888
TI  - The causes of failure of lumbar transpedicular spinal instrumentation and fusion:
      a prospective study.
AB  - A prospective study was made of 101 patients who underwent transpedicular spinal
      instrumentation and fusion of the lumbar spine. All were reviewed by an
      independent observer. The objectives were to determine the causes of clinical
      failure and to recommend preventive measures. Forty-two primary and 59 revision
      operations were performed. The average age was 46 years and follow up 4 years.
      The variable screw placement and Cotrel-Dubousset systems were used. Posterior
      lumbar interbody fusion was carried out in 24 patients. The outcome was
      satisfactory after primary operations in 67% and after revisions in 46%. Nerve
      root injuries due to screw placement occurred in 4% (2% permanent and 2%
      transient). Instrumentation-induced foraminal stenosis developed in 2%. Proper
      surgical technique can avoid these complications. Predictive factors for failure
      are: abnormal psychology, symptomatic epidural fibrosis, inadequate decompression
      of lateral stenosis, surgical complications and the use of allografts.

PMID- 8881889
TI  - Spinal fusion in situ in osteogenesis imperfecta.
AB  - Osteogenesis imperfecta in its most severe forms has a devastating effect on the
      peripheral and central skeleton, and patients are unable to walk. Spinal
      deformity is common and causes difficulty in sitting, pain and potentially life
      threatening complications. Instrumented spinal fusion might be considered the
      treatment of choice, but the bone may be too weak to sustain the implants and
      autogenous bone graft is poor in quantity and quality. We present the preliminary
      results of a technique of fusion without instrumentation and using Keil bone
      graft in 5 patients with severe osteogenesis imperfecta. The curve was stabilised
      and back pain relieved.

PMID- 8881890
TI  - Complications and technical problems with the gamma nail.
AB  - A retrospective review of complications with the gamma nail has been carried out
      in 152 patients with stable and unstable pertrochanteric fractures. Operative
      complications occurred in 10 patients. Screws penetrated the femoral neck in 3,
      immediate varus was associated with a short screw in 2, diaphyseal fractures
      occurred at the site of the distal screws in 3 and comminuted femoral fractures
      in 2. Fifteen patients (10.5%) died in hospital. At follow up, pseudarthrosis was
      present in 2 cases and fractures of the femoral shaft in 4. The incidence of
      complications could be reduced by using of shorter nails, less valgus angulation
      and by not introducing distal screws unless essential.

PMID- 8881891
TI  - Comparative biomechanics of the sliding screw-plate and the Bousquet nail-plate.
AB  - Four stable and 12 unstable trochanteric fractures were produced in human
      cadavers and fixed with either a sliding screw-plate or the Bousquet nail-plate.
      Axial cyclic loading showed that both implants were satisfactory for stable
      fractures. The sliding screw-plate withstood increased loads and the system
      failed at a later cycle in unstable fractures. Central placement of both the
      sliding screw or nail enhances stability, especially against torsional forces.

PMID- 8881892
TI  - Reconstruction femoral nailing for nonunion of subtrochanteric fracture: a
      revision technique following dynamic condylar screw failure.
AB  - We report two cases of nonunion of subtrochanteric fractures associated with
      failure of fixation with a dynamic condylar screw (DCS) due to plate fracture. In
      both cases the nonunion was successfully treated by insertion of a reconstruction
      femoral nail. This implant allowed early weightbearing despite the patients'
      advanced age and poor bone quality. We did not perform direct bone grafting and
      the fractures healed without complication.

PMID- 8881893
TI  - Management of primary idiopathic hyperphosphatasemia with calcitonin: a case
      report.
AB  - We describe a patient with primary idiopathic hyperphosphatasemia, a rare
      hereditary disease caused by a primary enzymatic disorder. The clinical,
      radiological, histological and biochemical features of the disease and their
      response to treatment with Calcitonin are described. We recommend Calcitonin for
      this rare disease in specialist units. It leads to improvement in many markers
      and better function.

PMID- 8881895
TI  - American College of Sports Medicine 43rd annual meeting. Cincinnati, Ohio, May 29
      June 1, 1996. Abstracts.

PMID- 8881894
TI  - Osteoid osteoma with a multicentric nidus.
AB  - A case is reported of a 16-year-old boy who presented with continuous pain in his
      right leg. Cortical thickening and diffuse medullary sclerosis was revealed on x
      ray of the distal tibia. CT imaging showed a circumscribed annular pattern
      extending some 2.5 cm-s and indicating the multifocal nature of the lesion. The
      diagnosis of multifocal osteoid osteoma was confirmed after histological
      examination of the block of resected bone.

PMID- 8881896
TI  - Neoral (cyclosporin) in dermatology: technical aspects.
AB  - Cyclosporin is a highly effective treatment for psoriasis, atopic dermatitis and
      many other inflammatory dermatoses. Absorption of cyclosporin from the
      traditional Sandimmun formulation is influenced by many factors, including bile
      flow, food and gastrointestinal motility. As a consequence, the bioavailability
      of Sandimmun is low and highly variable, both within and between patients. Neoral
      is a microemulsion preconcentrate formulation that has self-emulsifying
      properties and immediately forms a microemulsion in aqueous fluids, allowing
      rapid and consistent absorption of cyclosporin from the gastrointestinal tract.
      Benefits in dermatology are likely to be more patients responding at lower doses,
      a faster onset of action and a more predictable response to a given dose allowing
      for fewer dose adjustments. In the future these benefits of Neoral may lead to
      the simplified management of cyclosporin treatment and less frequent safety
      monitoring.

PMID- 8881897
TI  - Clinical aspects: preliminary experience with a novel oral formulation of
      cyclosporin (Neoral).
AB  - Cyclosporin has been shown to be highly effective in psoriasis, atopic dermatitis
      and numerous other dermatoses. Despite the effectiveness of cyclosporin, the
      response varies somewhat between individuals. Some may not respond, and often
      this is linked with unpredictable absorption of the traditional formulation.
      Cases of atopic dermatitis and psoriasis previously resistant to cyclosporin have
      responded well to a new microemulsified formulation, Neoral, and formal trials
      are now underway to investigate its use in these indications. Preliminary data
      from a clinical trial using the new formulation in chronic plaque psoriasis
      suggest that this has similar efficacy and tolerability to the traditional
      formulation in this condition, and that repeated short courses of therapy may be
      well tolerated.

PMID- 8881898
TI  - Comparison of the steady state pharmacokinetics of two formulations of
      cyclosporin in patients with atopic dermatitis.
AB  - A comparison was made of the efficacy, tolerability, safety and steady state
      pharmacokinetics of Sandimmun and Neoral in 11 stable atopic dermatitis patients
      already on Sandimmun. The study was of an open, crossover design. At entry into
      the trial, patients were switched to Neoral for 28 days. Treatment was switched
      back to Sandimmun for Days 28 to 42. The morning dose was given fasting, the
      evening dose after a standard meal. All measures of eczema severity improved
      during the Neoral treatment period. Neoral was markedly better tolerated with
      fewer side-effects. Switching from Sandimmun to Neoral at the same dose resulted
      in less variable pharmacokinetic profiles in both fasted and fed states. There
      was an increase in bioavailability with better, less variable and faster
      absorption, with a slightly reduced tmax, a higher mean Cmax (+43%) and a higher
      mean AUC (+30%) in fasted, but not fed patients. Higher trough levels (Cmin)
      occurred throughout for Neoral. These differences between the two formulations
      were not associated with any changes in safety parameters. Overall, Neoral was
      equivalent or superior to Sandimmun in tolerability and efficacy when given on a
      1:1 dose basis.

PMID- 8881899
TI  - The long-term safety and efficacy of cyclosporin in severe refractory atopic
      dermatitis: a comparison of two dosage regimens.
AB  - An open, randomized trial was performed to determine the optimal dosage schedule
      with regard to the efficacy and safety of cyclosporin in severe atopic
      dermatitis. The study also provided clinical experience with regard to the
      efficacy and safety of long-term cyclosporin treatment. During a 2-month dose
      finding period, 78 patients with severe, long-standing atopic dermatitis received
      cyclosporin at a dose of either 5 mg/kg per day, decreasing to 3 mg/kg per day
      (Group A), or 3 mg/kg per day, increasing to 5 mg/kg per day (Group B), Patients
      were maintained on their optimal dose for a further 10 months. Patients in Group
      A showed a significantly greater improvement in efficacy parameters over the
      first 2 weeks than with patients in Group B, but as the dose was decreased in
      Group A and increased in Group B, these differences were minimized. After 1 year,
      cyclosporin showed an efficacy of 59.8% in Group A and 51.7% in Group B, assessed
      by a severity score. Assessed in terms of an area score, these figures were 48.7%
      and 40%, respectively. Cyclosporin demonstrated a good safety profile during long
      term treatment and was generally well tolerated. The lower starting dosage was
      not associated with higher dropout rates. This study showed no differences in
      efficacy or adverse events between the two dosage schedules in long-term
      treatment.

PMID- 8881900
TI  - Treatment of severe atopic dermatitis in childhood with cyclosporin.
AB  - Cyclosporin has been shown to be effective in the treatment of adult atopic
      dermatitis, but there are no clinical trials evaluating its use in childhood.
      Atopic dermatitis is more common in children and the severe form can be
      associated with considerable morbidity. We report on 18 children with severe
      refractory atopic dermatitis who have been treated with cyclosporin on an open
      basis. The drug was given at an initial daily dose of 5 or 6 mg/kg and in some
      patients the dose was reduced according to response. Sixteen patients showed a
      good or excellent response to treatment, one a moderate response and one patient
      failed to improve. The treatment was well tolerated and there were no significant
      changes in serum creatinine or blood pressure. Long remission after withdrawal of
      treatment was seen in some patients, although most relapsed within a few weeks.
      We suggest that cyclosporin is an effective and safe short-term treatment for
      severe atopic dermatitis in childhood.

PMID- 8881901
TI  - Six area, six sign atopic dermatitis (SASSAD) severity score: a simple system for
      monitoring disease activity in atopic dermatitis.
AB  - The Six Area, Six Sign Atopic Dermatitis severity score has proved to be a simple
      and effective system for recording and monitoring disease activity in atopic
      dermatitis. The score is obtained by grading six signs (erythema, exudation,
      excoriation, dryness, cracking and lichenification), each on a scale of ()
      (absent), 1 (mild), 2 (moderate), or 3 (severe), at each of six sites; arms,
      hands, legs, feet, head and neck, trunk. The maximum score is 108.

PMID- 8881902
TI  - Individualized short-course cyclosporin therapy in psoriasis.
AB  - The efficacy and side-effects of cyclosporin in psoriasis, namely hypertension
      and renal dysfunction, are dose-related. An initial dose of 3 mg/kg per day has a
      better risk/benefit ratio than 5 mg/kg per day. Maximum efficacy is usually
      reached after 2-3 months, and effects of the drug remain even after treatment
      stops. We therefore suggest that periodic short-term use of cyclosporin in order
      to combine persisting therapeutic effect with safety. Psoriatic erythroderma and
      arthropathy also respond rapidly to oral cyclosporin. Once patients have been
      successfully treated, the drug should be discontinued. Treatment must not exceed
      6 months, but in the case of relapse a new cycle of the previously effective and
      tolerated dose can be given. The concomitant use of other therapies has been
      assessed in an attempt to reduce the dose of cyclosporin. There are no
      significant cyclosporin-sparing effects when etretinate or UVB are used
      adjunctively, and currently no convincing data on the risk of combining low-dose
      cyclosporin with immunosuppressive therapy (including methotrexate, UVB, and
      PUVA) in dermatological indications. The addition of topical corticosteroids or
      calcipotriol leads to more rapid clearing of psoriasis plaques, although relapse
      rates remain unchanged. Individualized short-course cyclosporin therapy is useful
      in controlling acute psoriasis flares and/or inducing remission; less potent
      agents can then be used for maintenance therapy. Short courses of low-dose
      cyclosporin may almost completely eliminate the risks of renal dysfunction from
      this drug.

PMID- 8881903
TI  - Increased bioavailability and improved efficacy, in severe psoriasis, of a new
      microemulsion formulation of cyclosporin.
AB  - Cyclosporin, as the microemulsion formulation Neoral, was given to two groups of
      patients with severe psoriasis (Psoriasis Area and Severity Index: PASI > 12.0).
      Group A (10 patients) were receiving the traditional formulation of cyclosporin,
      Sandimmun, at the start of the study, with a partial clinical response, and were
      switched to Neoral at the same dose (3.3 mg/kg per day). Group B patients, who
      had previously been treated with Sandimmun but were treatment failures, were
      given Neoral, 3.5 mg/kg per day. This led to rapid improvement in psoriasis in
      both groups. In Group A mean PASI fell from 22.3 to 11.6 on Sandimmun, after 82
      +/- 30 weeks, and to 4.0 (P < 0.05) after 32 weeks of Neoral. In Group B mean
      PASI decreased from 20.3 to 3.7 (P < 0.05) at a dose of 3.1 mg/kg per day.
      Pharmacokinetic data demonstrated significant decrease in tmax from 2.3 to 1.4
      hours. After 2 weeks Cmax and the area under the curve (AUC) (0-4 h) were
      significantly increased by 41% and 61%, respectively. Further pharmacokinetic
      data at 3 months showed similar results. No significant changes in renal function
      from pre-treatment status were seen in either group. None of the patients
      developed hypertension. No serious adverse events were reported. The
      microemulsion formulation of cyclosporin showed greater efficacy and
      bioavailability. Improved outcome was seen at doses which were on average 15%
      lower than with the traditional formulation, leading to a reduction in cost of
      treatment.

PMID- 8881904
TI  - Cyclosporin in less common immune-mediated skin diseases.
AB  - Cyclosporin represents a major step forward in the systemic treatment of various
      dermatoses. Psoriasis vulgaris and atopic eczema, the two major indications for
      the drug, are dealt with elsewhere in this issue. Therefore, this short review
      will focus on less common inflammatory skin diseases.

PMID- 8881905
TI  - The genetics of osteoarthritis.

PMID- 8881906
TI  - The pathology of osteogenesis imperfecta.

PMID- 8881907
TI  - Cytogenetics 40 years on.

PMID- 8881908
TI  - Immunisation policies--successes, failures and the future.

PMID- 8881909
TI  - Urinalysis in clinical diagnosis.

PMID- 8881910
TI  - Causes of death in osteogenesis imperfecta.
AB  - AIMS: To determine the causes of death in patients with osteogenesis imperfecta,
      excluding infants with the perinatal lethal form (type II). METHODS: Seventy nine
      patients with known osteogenesis imperfecta were identified, 37 of whom had been
      seen clinically in life. Causes of death were identified from death certificates,
      postmortem reports, medical records, hospital consultants, relatives, and the
      Brittle Bone Society's records. RESULTS: Patients with the milder types of
      osteogenesis imperfecta, I and IV, often had a normal lifespan and died of
      unrelated illnesses such as myocardial infarction and malignancy. In some of
      these patients and in many patients with the more severe type III disease, it was
      clear that osteogenesis imperfecta contributed significantly to death, almost
      certainly to many of the respiratory deaths and to deaths from cardiac failure
      due to kyphoscoliosis. Osteogenesis imperfecta also caused six deaths, directly
      or indirectly, due to basilar invagination of the skull. Osteogenesis imperfecta
      may have contributed to deaths from intracranial bleeding. Apparently minor
      traumatic incidents may have disastrous consequences in patients with this
      disorder. CONCLUSIONS: Prompt care for respiratory infections and prevention of
      trauma in patients with osteogenesis imperfecta is essential.

PMID- 8881911
TI  - Detection of herpesvirus-like DNA by nested PCR on archival skin biopsy specimens
      of various forms of Kaposi sarcoma.
AB  - AIMS: To detect herpesvirus-like DNA sequences, defining a new herpesvirus, human
      herpesvirus 8 (HHV8), in paraffin wax embedded skin biopsy specimens of the
      various forms of Kaposi sarcoma. METHODS: DNA was extracted from archival skin
      biopsy specimens of Kaposi sarcoma, other mesenchymal skin tumours and various
      inflammatory skin lesions of HIV seropositive and negative patients. HHV8 DNA was
      detected by using a nested PCR assay. Human beta-globin DNA served as an internal
      control. RESULTS: Twenty two samples of Kaposi sarcoma were analysed, comprising
      12 of the endemic type, nine HIV associated and one transplantation related. HHV8
      DNA was detected by nested PCR in all forms of Kaposi sarcoma. By contrast, no
      HHV8 DNA was detected in five mesenchymal skin tumours or nine biopsy specimens
      of unspecific inflammatory skin lesions of HIV seropositive and negative
      patients. CONCLUSIONS: Detection of HHV8 DNA in paraffin wax embedded tissue can
      be used to confirm a diagnosis of Kaposi sarcoma.

PMID- 8881912
TI  - Serum lipid, lipoprotein and apolipoprotein changes in gestational diabetes
      mellitus: a cross-sectional and prospective study.
AB  - AIMS: To compare serum lipid, lipoprotein and apolipoprotein concentrations
      during and six to 12 months after pregnancy in control and diabetic women.
      METHODS: The serum lipid, lipoprotein and apolipoprotein concentrations were
      measured in 20 women with gestational diabetes mellitus (GDM) and 22 women with
      normal glucose tolerance (controls) during the third trimester of pregnancy and
      six to 12 months after delivery. RESULTS: During pregnancy the women with GDM had
      higher serum triglyceride (mean (95% confidence interval (CI)), 2.91 (2.22-3.51)
      v 2.1 (1.75-2.52)) but lower low density lipoprotein (LDL) cholesterol
      concentrations compared with controls (mean (SD), 3.08 (1.2) v 4.01 (1.1). Total
      cholesterol, high density lipoprotein (HDL) cholesterol and apolipoprotein
      concentrations were not significantly different between the two groups. After
      pregnancy, total cholesterol, HDL cholesterol, triglyceride, and apolipoprotein
      A1 and B decreased in a parallel manner, resulting in lower concentrations,
      comparable between the two groups. LDL cholesterol concentrations decreased after
      pregnancy in the controls (mean (SD), 4.01 (1.1) v 2.69 (0.6)) but not in those
      with GDM (3.08 (1.2) v 2.72 (0.7)). The change in lipid concentrations was not
      related to change in weight. CONCLUSION: Development of diabetes during pregnancy
      induces a state of dyslipidaemia characterised by elevated triglyceride
      concentrations, as seen in other insulin resistance states. However, GDM seems to
      blunt the increase in LDL cholesterol during pregnancy and this requires further
      investigation. Whether the changes in lipoprotein metabolism in GDM are
      significant for the health status of the mother and the foetus requires further
      study.

PMID- 8881913
TI  - Solid tissue culture for cytogenetic analysis: a collaborative survey for the
      Association of Clinical Cytogeneticists.
AB  - AIMS: To survey the diagnostic service provided by UK laboratories for the
      culture of solid tissue samples (excluding tumours) and in particular to examine
      the variation in culture success rates and the problems of maternal cell
      overgrowth. METHODS: Twenty seven laboratories took part in a collaborative
      survey during 1992. Each laboratory submitted data on up to a maximum of 60
      consecutive specimens (n = 1361) over a six month period. RESULTS: Skin
      specimens, the largest category received (n = 520), were the most problematic
      (51% success rate). Culture success rates were significantly lower (43%) when
      skin specimens (n = 140) were transported dry to the laboratory. Success rates
      for skin specimens also varied, depending on the origin of the specimen, from 18%
      for intra-uterine deaths (IUD) (n = 94) to 85% for neonatal deaths (n = 33) and
      83% for live patients (n = 54). Culture of selected extra-fetal tissues from IUD,
      stillbirths and following elective termination of pregnancy (TOP) gave comparable
      success rates to those achieved for skin samples from neonatal deaths and live
      births. Skewed sex ratios, female > male, were identified for products of
      conception (POC) (n = 298) and placental biopsy specimens (n = 97). CONCLUSIONS:
      By appropriate selection, transport and processing of tissues, and in particular
      by avoiding relying solely on skin samples from IUD, stillbirths and TOP, an
      increase in culture success rates for solid tissue samples submitted for
      cytogenetic analysis could be achieved. The high risk of maternal cell
      contamination from POC and placental biopsy specimens was also identified in this
      survey.

PMID- 8881914
TI  - Antigen capture ELISA for the heat shock protein (hsp60) of Chlamydia
      trachomatis.
AB  - AIMS: To develop an indirect ELISA using the heat shock protein (hsp60) of
      Chlamydia trachomatis as antigen. METHODS: The hsp60 gene was amplified by PCR,
      expressed in the vector pDEV-107 and transformed into Escherichia coli. The
      recombinant protein, expressed as a beta-galactosidase fusion product, was
      captured onto a solid phase using a monoclonal antibody directed against beta
      galactosidase. Following incubation with goat anti-human antibody conjugated to
      peroxidase and colour development on addition of peroxidase substrate, antibody
      recognition of antigen was quantified by optical density at 492 nm. RESULTS: A
      sensitive and relatively specific ELISA to detect hsp60 has been produced, which
      can be exploited to determine the antibody response to C trachomatis hsp60.
      CONCLUSIONS: This assay will permit the future investigation of the
      immunopathogenesis of persistent inflammation following C trachomatis infection.

PMID- 8881916
TI  - A comparison of pathological methods of measuring lung cancer volume.
AB  - AIM: To determine which of several pathological methods of measuring lung cancer
      volume compared most favourably with the gold standard. METHODS: Three
      pathological methods were used on 54 resected lung cancers: (1) measuring the
      maximum dimension and assuming a spherical shape; (2) measuring three dimensions
      and assuming an ellipsoidal shape; and (3) deriving the volume from the area of
      tumour on sequential 1 cm slices using a photocopier and an image analysis
      system. The gold standard was obtained from the area of whole mount tumour
      sections on sequential 0.1 cm slices of eight cancers. RESULTS: Volumes derived
      from 1 cm lung slices gave results closest to our gold standard but assuming
      tumours were ellipsoidal was only a slightly less accurate and less time
      consuming method. Assuming cancers were spherical resulted in gross
      overestimation of the tumour volumes. CONCLUSIONS: For practical purposes, it is
      reasonable to measure three dimensions of a lung tumour at sectioning and
      calculate the volume using the formula for an ellipsoid (V = 4/3 pi d.e.f, where
      d, e and f are the semi-axes).

PMID- 8881915
TI  - p53 protein expression in malignant, pre-malignant and non-malignant lesions of
      the lip.
AB  - AIM: To elucidate the role of the p53 tumour suppressor gene in the pathogenesis
      of lip cancer. METHODS: Expression of p53 was evaluated immunocytochemically in a
      retrospective study of formalin fixed, paraffin wax embedded tissue. Five cases
      each of four types of lip lesions were studied; these comprised squamous cell
      carcinoma (SCC), solar keratosis (SK), chronic hyperplastic candidosis (CHC), and
      lichen planus (LP). Five cases each of normal lip mucosa, SCC, and SK from sun
      exposed facial skin as well as LP, CHC, and SCC from buccal mucosa were also
      analysed. Immunolocalisation of p53 was scored semiquantitatively. The degree of
      apoptosis was also assessed in selected lesions by determining cell nuclear
      fragmentation. RESULTS: All SCCs from lip lesions were immunopositive for p53.
      All cases of SK and two of five CHC lip lesions were also p53 positive. Normal
      lip mucosa samples were p53 negative. Sun exposed skin lesions of SCC and SK were
      all positive for p53, but only three of five cases of SCC from the buccal mucosa
      had detectable levels of p53. p53 expression was not detected in CHC and LP
      lesions of the buccal mucosa. CONCLUSIONS: The aberrant expression of p53 is
      likely to occur early in the pathogenesis of lip cancer and may be related to
      exposure to the sun. The immunopositive p53 cells identified in the benign LP
      lesions do not necessarily correlate with commitment of cells within the lesion
      to programmed cell death. In light of the prior reports which indicate that p53
      positive cells may progress to form malignant tumours, it is suggested that
      patients with p53 positive but otherwise benign lesions should be followed more
      closely.

PMID- 8881917
TI  - Proliferating cell nuclear antigen expression in papillary thyroid carcinoma.
AB  - AIMS: To correlate the expression of proliferating cell nuclear antigen (PCNA)
      with various clinicopathological features of papillary thyroid carcinoma.
      METHODS: Sections from 131 formalin fixed, paraffin wax embedded papillary
      thyroid carcinomas were stained with a monoclonal antibody (PC10) directed
      against PCNA using the avidin-biotin immunoperoxidase (ABC) method. PCNA
      immunoreactivity was based on the PCNA labelling index (LI) following evaluation
      of at least 1000 tumour cells, and expressed as follows: grade A (LI < 10%),
      grade B (10% < or = LI < 25%), and grade C (LI > or = 25%). The relation between
      PCNA expression in these three groups and other clinicopathological factors, such
      as sex, age, tumour size, nodal metastases, and histological differentiation,
      were examined. RESULTS: Based on the labelling index, 57 (43.5%) cases were
      graded as A, 46 (35.1%) as B, and 28 (21.4%) as C. The female-:male ratios were
      6.13:1 for group A, 2.83:1 for group B, and 2.11:1 for group C. The mean (SD)
      ages of the patients were 39.0 (16.1) in group A, 53.5 (14.4) in group B, and
      55.8 (13.3) years in group C. The correlation between age and PCNA grade was
      strongest in women. CONCLUSIONS: PCNA immunoreactivity is correlated with sex and
      age in patients with papillary thyroid tumours.

PMID- 8881918
TI  - Expression of IL-2R, IL-4R, IL-6R on peripheral blood lymphocytes in systemic
      lupus erythematosus and correlation with disease activity: a prospective study.
AB  - AIMS: To study the expression of interleukin-2 receptor (IL-2R), interleukin-4
      receptor (IL-4R) and interleukin-6 receptor (IL-6R) on peripheral blood
      lymphocytes (PBL) in patients with systemic lupus erythematosus (SLE); to
      correlate the level of expression of these receptors with SLE disease activity.
      METHODS: Peripheral blood lymphocytes were studied by a high sensitivity flow
      cytometry technique using monoclonal antibodies directed against CD25 (IL-2R
      alpha chain), CD122 (IL-2R beta chain), CD124 (IL-4R), and CD126 (IL-6R). SLE
      disease activity was scored using the SLE Disease Activity Index, C3 and C4
      concentrations, anti-dsDNA level, and absolute lymphocyte count. RESULTS:
      Compared with normal controls, PBL from patients with SLE had a higher percentage
      of CD25+ cells (median 20.8% v 16.5%) and a lower percentage of CD122+ cells
      (median 13.1% v 22.4%). The difference in CD122+ cells was greater in the
      CD122weak population than the CD122strong (natural killer cell) population. The
      percentages of CD124+ and CD126+ PBLs in patients with SLE and controls were
      similar. On CD25+ cells, the relative antigenic level of the IL-2R alpha chain
      was significantly higher in patients with SLE (median 2.01 v 1.81). The relative
      antigenic levels of CD122+, CD124+ and CD126+ cells were similar in patients and
      controls. Neither the percentages nor the relative antigenic levels of all of
      these cytokine receptors were correlated with any of the parameters of disease
      activity. CONCLUSION: Lymphocyte activation in patients with SLE was evident from
      the increase in CD25 expression on PBL, with a reciprocal decrease in CD122
      expression. As the expression of IL-2R, IL-4R, IL-6R did not correlate with
      disease activity, it seems that these cytokine/receptor systems do not play a
      direct role in disease activation in SLE.

PMID- 8881919
TI  - Ethnic and sex differences in the total and differential white cell count and
      platelet count.
AB  - AIM/BACKGROUND: Previous studies have suggested that healthy subjects of African
      ancestry have lower total white cell counts, neutrophil counts and platelet
      counts than Caucasian subjects and that, at least among Caucasians, women have
      higher neutrophil and platelet counts than men. The primary aim of this study was
      to confirm and quantify the ethnic differences, confirm the sex difference in
      Caucasians and determine whether there was a similar sex difference in non
      Caucasians. A secondary aim was to establish reference ranges for white cell and
      platelet counts for the different ethnic and sex groups. METHODS: The study
      population comprised 417 healthy volunteers (201 women and 216 men), of whom 200
      were Caucasian, 102 were Afrocaribbean and 115 were African. Full blood counts,
      including a differential white cell count, were measured using a H.2 automated
      differential counter. White cell and platelet counts were compared between the
      three different ethnic groups and between men and women. Reference ranges were
      determined for each ethnic and sex group. RESULTS: Africans and Afrocaribbeans
      had lower total white cell, neutrophil and platelet counts than Caucasians and
      counts were lower in Africans than in Afrocaribbeans. Women had higher neutrophil
      and platelet counts than men in all ethnic groups. CONCLUSIONS: Sex and ethnic
      origin should be taken into consideration when assessing white cell and platelet
      counts.

PMID- 8881920
TI  - Proliferation in the normal cervix and in preinvasive cervical lesions.
AB  - AIMS: To characterise further the proliferative compartment of the normal cervix
      and to document its alteration, if any, in the various grades of cervical
      intraepithelial neoplasia (CIN), particularly changes to the basal epithelial
      layer; to hypothesise as to the diagnostic and biological significance of any
      observed differences. METHOD: Proliferative compartments from 86 cervical biopsy
      specimens (10 normal, 11 with koilocytic change only, 12 CIN I, nine CIN II, and
      44 CIN III) were determined using microwave antigen retrieval and a standard
      three-step Streptavidin biotin peroxidase immunocytochemical technique
      incorporating the MIB-1 monoclonal antibody (directed against the Ki-67 antigen).
      Immunoreactivity was assessed as occupying either the lower one third, lower two
      thirds or all three thirds of the squamous epithelium. Basal cell positivity was
      also quantitated. RESULTS: Specimens without CIN showed a thin suprabasal
      proliferative compartment two to four cells thick. True basal positivity was
      infrequent. With increasing grade of CIN, the growth compartment stretched
      evermore superficially so that in lesions of CIN III almost the full thickness of
      epithelium was cycling. In all grades of CIN, basal cell proliferation was
      significantly increased. CONCLUSIONS: In normal cervix, the parabasal layers
      represent the main proliferative pool with the basal layer providing a reserve.
      When CIN supervenes, this proliferative compartment expands commensurate with the
      grade of dysplasia and as basal turnover is increased specifically the intimate
      relation between epithelium and basement membrane might be disturbed,
      facilitating invasion. The diagnostic utility of these changes in growth
      compartments is limited.

PMID- 8881921
TI  - Assessment of IgH PCR strategies in multiple myeloma.
AB  - AIMS: To compare the ability of four commonly used PCR techniques to demonstrate
      clonal IgH rearrangements in multiple myeloma. METHODS: Bone marrow samples
      (containing a minimum of 10% plasma cells) were obtained from 127 patients with
      confirmed multiple myeloma. Framework 3 (Fr3) PCR was performed in all cases and
      the Framework 1 (Fr1f) PCR, which utilises six VH family specific primers, in 98
      cases. In addition, 44 cases were assessed by Fr3, Fr1f, Framework 2 (Fr2) and
      Framework 1 consensus (Fr1 con) PCR techniques. JH primer selection was also
      assessed such that each PCR strategy was performed twice in each of the 44 cases,
      using the JH consensus primer (JH con) alone and then repeated with an equimolar
      mixture of JH con, JH3 and JH6 (JH mix). RESULTS: Clonal rearrangements were
      demonstrated in 71 (56%) of 127 cases with the Fr3 PCR and in 52 (53%) of 98 with
      the Fr1f PCR. However, by using both techniques it was possible to demonstrate
      clonal IgH rearrangements in 92 (75%) of 122 cases. Forty four cases were
      assessed by all four PCR techniques; in these cases the Fr3 and Fr1f PCRs
      demonstrated clonal rearrangements in 26 (59%) cases with a combined yield of 34
      (77%). The Fr2 and Fr1 con PCR techniques had inferior pick up rates,
      demonstrating clonal rearrangements in 21 (48%) of 44 cases and a combined yield
      of 28 (63%). The Fr2 PCR did, however, demonstrate a clonal rearrangement in one
      case negative by both Fr3 and Fr1f. Two additional rearrangements were
      demonstrated by using JH mix; one became positive by Fr3, Fr1f and Fr2 and the
      other positive by Fr1f, Fr1 con and Fr2. CONCLUSIONS: By utilising both the Fr3
      and Fr1f PCR techniques it is possible to demonstrate definitive clonal
      rearrangements in the majority of patients with multiple myeloma. The Fr1 con and
      Fr2 PCR techniques have inferior pick up rates but may detect some additional
      rearrangements.

PMID- 8881922
TI  - Insulin-like growth factor-I in Helicobacter pylori gastritis and response to
      eradication using bismuth based triple therapy.
AB  - AIMS: To measure insulin-like growth factor-I (IGF-I) concentrations in the
      presence and absence of Helicobacter pylori infection and in response to
      eradication of the organism. METHODS: An enzyme linked immunosorbent assay was
      used to measure gastric and fasting serum concentrations of IGF-I in 17 patients
      with and 11 without H pylori infection. Repeat assessments were performed in the
      infected patients six weeks after they received a two week course of bismuth
      chelate, metronidazole, and amoxycillin. RESULTS: IGF-I was detected at very low
      concentrations in gastric juice and in mucosal incubates. The median serum IGF-I
      concentration was 88 micrograms/l in the patients infected with H pylori compared
      with 90 micrograms/l in the non-infected controls; IGF-I concentrations dropped
      to 77 micrograms/l following eradication therapy (p = 0.014). CONCLUSION: The
      similarity in baseline IGF-I concentrations in the presence and absence of H
      pylori suggests that their subsequent drop after treatment is more likely to be
      due to the treatment.

PMID- 8881924
TI  - Hypophosphatasia.
AB  - Hypophosphatasia is a rare inherited metabolic disease characterised by reduced
      plasma and tissue alkaline phosphatase activity, and may present in infancy,
      childhood or adulthood. The differing modes of inheritance, presentation and
      natural history are likely to reflect variable expression of the alkaline
      phosphatase gene defect. A case of infantile hypophophatasia presenting with
      hypercalcaemia is described and the histological and radiological resolution of
      the mineralisation defect present initially are reported.

PMID- 8881923
TI  - Electron microscopy and serological features of a patient with Q fever prosthetic
      valve endocarditis.
AB  - The clinical, serological and electron microscopic findings in a 47 year old
      woman with bioprosthetic valve coxiella endocarditis occurring 15 years after
      streptococcal endocarditis are described. The patient underwent valvular surgery
      a total of four times to control symptoms and remains well on medical therapy
      more than two years after her last operation.

PMID- 8881925
TI  - Does storage of sputum specimens adversely affect culture results?
AB  - It has been recommended that samples submitted for microbiological examination
      should be retained for 48 hours after issue of the final report. In order to
      ascertain whether reproducible results could be achieved following storage of
      sputum specimens, two laboratories each re-cultured 100 samples 48 hours after
      their report had been issued and a further laboratory re-cultured 100 samples 48
      hours after receipt. Discordant results were obtained in only 5-25% of specimens,
      indicating that potential respiratory pathogens could survive storage.

PMID- 8881926
TI  - Isolation of Mycoplasma hominis using the BACTEC 9000 series blood culture
      system.
AB  - Mycoplasma hominis has been implicated as an important cause of septicaemia.
      There have been reported variances in the ability of blood culture systems to
      support the growth of this organism. In this study the ability of the BACTEC 9000
      series automated system to grow and detect M hominis was assessed. Three of five
      wild M hominis strains grew in the BACTEC Anaerobic Plus/F medium but growth was
      not flagged by the detection mechanism of the system. It is recommended that
      users of the BACTEC 9000 series should use a seven day protocol and perform
      terminal subculture for suspected cases of M hominis septicaemia.

PMID- 8881927
TI  - Heat tolerance of vancomycin resistant Enterococcus faecium.
AB  - The heat tolerance of 27 Enterococcus faecium isolates in water was studied.
      Stationary phase cultures including vancomycin resistant and sensitive clinical
      and food isolates were exposed to heat at 60 degrees, 65 degrees, 71 degrees, and
      80 degrees C for one, three, 10, and 30 minutes and the log10 reductions in
      bacterial counts were determined. Exposure at 71 degrees and 80 degrees C
      resulted in > 6 log10 reduction in viable counts for all isolates. Seven (24%)
      isolates survived (< 5 log10 reduction) heat at 65 degrees C for 10 minutes. The
      E faecium isolates were more resistant to heat than the two E faecalis reference
      strains. No differences in heat tolerance were observed between vancomycin
      sensitive and resistant strains or between isolates of human or food origin.

PMID- 8881928
TI  - The hidden increase in histopathologists' workload.
AB  - The informational content of histopathological reports generated between 1985 and
      1995 was assessed. This showed an exponential rise over the past five years. It
      is postulated that this has arisen from developments in medical science and
      demands from clinical colleagues. This increase in workload is not addressed by
      present methods of measurement and has major resource implications.

PMID- 8881929
TI  - Central review of bone marrow biopsy specimens from patients with neuroblastoma.
AB  - In order to achieve some uniformity in histological detection of bone marrow
      infiltration by neuroblastoma and to provide a measure of variation in
      histological opinions, sections from 712 evaluable trephine biopsy cores from
      children in a European Neuroblastoma Study Group (ENSG) study were reviewed
      centrally. Biopsy specimens were graded as tumour positive or negative.
      Discordance between local and central review opinions was found in 5% of
      specimens. Only five of 165 children at presentation and nine of 256 re-staging
      procedures in 126 children, affecting one child each, had their diagnosis
      upgraded to positive. In six re-staging procedures, affecting one child each, the
      diagnosis was downgraded. The low discordance rate is encouraging and
      substantially less important than previously documented difficulties in obtaining
      adequate specimens.

PMID- 8881930
TI  - Phraseology in quality assurance reports.

PMID- 8881931
TI  - Phraseology in quality assurance reports.

PMID- 8881932
TI  - beta hCG as a prognostic marker in prostatic adenocarcinoma.

PMID- 8881933
TI  - Current guidelines for sampling the cervix in hysterectomy specimens are
      appropriate.

PMID- 8881934
TI  - Specificity of plasma cell antibody VS38.

PMID- 8881935
TI  - Confidentially, death and the doctor.

PMID- 8881936
TI  - Peritoneal involvement by rectal cancer.

PMID- 8881937
TI  - Phytotherapy for the prostate.

PMID- 8881938
TI  - The relevance of p53 mutation in urological malignancies: possible clinical
      implications for bladder cancer.

PMID- 8881939
TI  - Clinical, radiological and histological features of adrenal myelolipoma: review
      and experience with a further eight cases.
AB  - OBJECTIVE: To review published reports of surgically treated adrenal myelolipomas
      and report experience with a further eight cases. PATIENTS AND METHODS: Eight
      patients (three men and five women, mean age 50.7 years) with adrenal myelolipoma
      were treated surgically because of the tumour size, symptomatology and/or
      associated renal pathology. Associated medical problems included hypertension in
      three patients and diabetes mellitus in one but none of the tumours was
      endocrinologically active. RESULTS: Five patients were diagnosed definitively by
      abdominal ultrasonography, computed tomography and angiography while the other
      three were incidentally diagnosed during surgical intervention for ipsilateral
      renal cell carcinoma in one patient, hydronephrotic kidney in another and
      multiple renal stones in the third. On pathological examination, the masses
      removed were surrounded by a thin fibrous capsule and compressed cortical tissue.
      A cut section was bright yellow with foci of red-brown discoloration.
      Microscopically, the tumour consisted mainly of mature adipose tissue with
      scattered islands of haemopoietic cells. There was no operative mortality and no
      gross morbidity. CONCLUSION: The management of adrenal myelolipoma should be
      appropriate to each individual case. Operative intervention should be reserved
      for symptomatic patients or those with large 'silent' tumours that may produce
      life-threatening shock secondary to spontaneous haemorrhage. Small asymptomatic
      tumours with definite radiological findings can be followed expectantly.

PMID- 8881940
TI  - Incidentally detected renal cell carcinoma: pathological features, survival
      trends and implications for treatment.
AB  - OBJECTIVES: To compare treatment outcomes in symptomatic and incidental renal
      cell carcinoma (RCC) with specific interest in the role of radical nephrectomy.
      PATIENTS AND METHODS: The records of 189 patients with a clinical diagnosis of
      RCC were reviewed. The mode of presentation, tumour size, grade and stage at
      presentation were correlated with final outcome, as measured by the disease-free
      and overall survival of the patients. RESULTS: The rate of incidental detection
      was 15%; incidental tumours were of a lower stage and patients with incidentally
      detected tumours had a significantly longer disease-free and overall survival
      than had those with symptomatic tumours (P < 0.05). CONCLUSIONS: The increased
      detection of incidental tumours should further improve survival in RCC. We
      continue to advocate radical nephrectomy for incidentally detected tumours, as it
      offers the best outcome and simplifies the follow-up.

PMID- 8881941
TI  - Wegener's granulomatosis involving the urogenital tract.
AB  - OBJECTIVE: To report eight cases of limited Wegener's granulomatosis (WG)
      affecting the urogenital tract (testis, ureter, bladder, urethra and penis) and
      to emphasize the importance of the anti-neutrophil cytoplasm antibody (ANCA) test
      in establishing the diagnosis. PATIENTS AND METHODS: Eight patients (six men and
      two women, aged 41-77 years) were diagnosed with WG, based on their previous
      medical history, the ANCA test and by biopsy. RESULTS: In each case, there were
      difficulties and delay in establishing the diagnosis of WG and starting
      appropriate treatment. The ANCA test was positive in seven cases and helped in
      establishing the diagnosis, in conjunction with the confirmation of vasculitis
      and granulomata by biopsy. CONCLUSION: We advocate ANCA testing in patients
      presenting with limited urogenital disease in association with a past or present
      relevant history of arthritis, skin vasculitis and/or biopsies showing necrosis
      or non-specific inflammation.

PMID- 8881942
TI  - Primary psoas abscess--diagnostic and therapeutic considerations.
AB  - OBJECTIVE: To present our experience of the diagnosis and treatment of primary
      psoas abscess in India. PATIENTS AND METHODS: Between July 1993 and December
      1995, five men (aged 24-67 years) presented with suspected primary psoas abscess.
      All five patients had fever with or without rigors and upper/lower abdominal pain
      of varying duration (2-6 weeks). RESULTS: The presentation in all patients was
      conspicuous by the absence of the classical signs of limping and positive psoas
      symptoms. Computed tomography (CT) was the best method of diagnosis, being
      accurate in every case. Antibiotics alone (two patients), or in combination with
      percutaneous aspiration, were curative. CONCLUSIONS: This small series of five
      patients of primary psoas abscess was remarkable in that all the patients were
      men and three were elderly. The classical symptom of limping was absent in all.
      The urologist can be misled by loin pain and irritative lower urinary symptoms in
      the patients, resulting in a delay in diagnosis and management.

PMID- 8881943
TI  - Expression of multidrug resistance-related genes (mdrl, MRP, GST-pi and DNA
      topoisomerase II) in urothelial cancers.
AB  - OBJECTIVE: To characterize the multidrug resistance (MDR) phenotype in human
      urothelial cancers, the expression levels of four MDR-related genes (multidrug
      resistance, mdrl; multidrug resistance-associated protein, MRP; glutathione S
      transferase-pi, GST-pi; and DNA topoisomerase II, topo II) were analysed in
      urothelial cancers. MATERIALS AND METHODS: Fifty-two tumour tissue and three
      normal urothelial mucosa samples were obtained from 44 patients with urothelial
      cancers. The expression of each gene was analysed with a reverse-transcription
      polymerase chain reaction (RT-PCR) method using beta 2-microglobulin (b2m) mRNA
      as an endogenous control. Levels of expression were expressed as the ratio of the
      specific products of the target gene to those specific to b2m. RESULTS: In
      primary urothelial cancer tissues, the mean (SD) expression of mdrl, MRP, GST-pi
      and topo II relative to b2m expression were 0.067 (0.061), 0.27 (0.23), 0.35
      (0.31) and 0.12 (0.05), respectively. The mean expressions of MRP and GST-pi were
      higher than those of mdrl and topo II. The mean ratios of mdrl/b2m, MRP/b2m, GST
      pi/b2m and topo II/b2m in normal urothelial mucosa were 0.06 (0.03), 0.12 (0.09),
      0.30 (0.32) and 0.14 (0.01), respectively. There was no significant association
      of the expression of each gene with either the grade or extent of the primary
      tumour. The level of MRP expression in each sample was correlated significantly
      with the expression of mdrl and GST-pi in the urothelial cancers (r = 0.637 and
      0.537, respectively). Chemotherapy did not markedly influence the induction of
      expression of the MDR-related genes, except for one case in which mdrl expression
      was 15 times greater than before chemotherapy. The expression of GST-pi in the
      patients not receiving chemotherapy was significantly higher than in those that
      did. CONCLUSIONS: These results suggest that the activation of MRP and GST-pi
      expression occurs during the tumorigenesis of urothelial cancers and that it may
      confer de novo and acquired drug resistance on urothelial cancers. These results
      should provide further insight into the complex role postulated for MDR-related
      genes in chemotherapy, carcinogenesis and tumour progression.

PMID- 8881944
TI  - Quality of life in patients undergoing bacille Calmette-Guerin therapy for
      superficial bladder cancer.
AB  - OBJECTIVE: To determine the impact of post-operative education about bladder
      cancer and topical immunotherapy on the physical, psychological and social well
      being of patients with superficial bladder cancer. PATIENTS AND METHODS: Eighty
      five patients (mean age 59 years, range 26-85, 64 men and 21 women) receiving
      topical immunotherapy were questioned during the initial cycle of treatment and
      during maintenance therapy with bacille Calmette-Guerin (BCG). Patients completed
      a questionnaire on their quality of life when they commenced treatment and twice
      more during maintenance therapy. RESULTS: Psychological distress and physical
      symptoms were intense when the diagnosis of bladder cancer was revealed to the
      patients, despite the knowledge that this cancer is usually curable. The overall
      quality of life, condition of health and sexual activity were mostly only
      moderate, were poor during initial therapy and better during 3-monthly
      maintenance therapy. CONCLUSION: In general, the quality of life of these
      patients is characterized by the disruption of their lifestyle and marked by
      change in their circumstances. It is the responsibility of the urologist to take
      the necessary time to educate, comfort and motivate such patients with
      superficial bladder cancer.

PMID- 8881945
TI  - The management of superficial bladder cancer: an interactive seminar.
AB  - OBJECTIVES: To determine the current management of superficial bladder cancer in
      the United Kingdom. METHODS: An interactive seminar with a series of questions
      about management and hypothetical clinical scenarios was conducted at the 1995
      conference of the British Association of Urological Surgeons. The responses of
      the audience were recorded electronically and analysed. RESULTS: The results
      showed that there is a wide variation in practice and some confusion over the
      place of intravesical treatment using cytotoxic drugs and bacille Calmette
      Guerin. CONCLUSIONS: The management of superficial bladder cancer could be
      improved by a more widespread use of intravesical therapy, along with the
      introduction of local protocols and national guidelines.

PMID- 8881946
TI  - The safety of finasteride used in benign prostatic hypertrophy: a non
      interventional observational cohort study in 14,772 patients.
AB  - OBJECTIVE: To examine the safety of finasteride as used in general medical
      practice to treat benign prostatic hypertrophy (BPH). PATIENTS AND METHODS:
      Information was collected on 14,772 patients who were included in an
      observational cohort study conducted using Prescription-Event Monitoring.
      RESULTS: Finasteride was reported to have been effective in 60% of the patients
      in whom an opinion on efficacy was recorded. Impotence or ejaculatory failure was
      reported in 2.1% of the patients, decreased libido in 1% and gynaecomastia and
      related conditions in 0.4%. Impotence was the most frequent reason for stopping
      treatment with finasteride and was the most commonly reported adverse reaction to
      the drug. Of the patients included in the elderly cohort involved in this study,
      819 (5.5%) died; none of these deaths was attributed to finasteride. CONCLUSION:
      Impotence or ejaculatory failure, decreased libido and gynaecomastia in a small
      proportion of patients were associated with the use of finasteride. The results
      of this study strongly suggest that this drug is acceptably safe when used in
      accordance with the current prescribing information.

PMID- 8881947
TI  - Improved reliability of uroflowmetry investigations: results of a portable home
      based uroflowmetry study.
AB  - OBJECTIVES: To compare the results obtained using a portable home-based
      uroflowmeter with the results of traditional flowmetry performed in the out
      patient department (OPD). PATIENTS AND METHODS: Sixty-seven patients (mean age 61
      years, range 38-79) with lower urinary tract symptoms and/or benign prostatic
      enlargement used a home-based uroflowmeter comprising a datalogger and specially
      designed fluid sensors incorporated into disposable beakers. The results of these
      measurements were compared with those from uroflowmetry in the OPD and with other
      clinical variables. RESULTS: There was a good correlation between the uroflow
      results obtained when voiding at home and at the OPD. The highest measured
      maximum flow and voided volume were obtained with the home-based uroflowmeter
      system. However, the mean of all consecutive home-based maximum flow and voided
      volume measurements were lower than those obtained by single-void uroflowmetry in
      the OPD. CONCLUSIONS: Home-based uroflowmetry provides reliable voiding results
      which are comparable with those obtained in the OPD.

PMID- 8881948
TI  - The role of an advanced thermotherapy device in prostatic voiding dysfunction.
AB  - OBJECTIVES: To investigate the efficacy of an advanced transurethral
      thermotherapy (TUMT) device (T3, Urologix) using urodynamic analysis in addition
      to the standard evaluation protocol in patients with symptomatic benign prostatic
      hyperplasia (BPH). PATIENTS AND METHODS: Fifty men with symptomatic BPH were
      assessed using the AUA symptom score, uroflowmetry and ultrasonography (to
      determine prostatic volume and residual urinary volume) before and 6 weeks, 3, 6
      and 12 months after thermotherapy. TUMT was delivered using a focused microwave
      energy system for 1 h in each patient, treated on an out-patient basis. Video
      pressure flow studies with advanced urodynamic analysis were also performed
      before and 3 months after treatment. RESULTS: The mean AUA symptom score
      decreased by 63%, the mean peak flow rate increased by 64% and the post-void
      residual volume decreased by 30% 3 months after treatment; this improvement was
      maintained at one year after treatment. Advanced urodynamic analysis showed that
      52% of the patients had a decreased severity of obstruction. Furthermore, the
      efficiency of detrusor contraction improved in 86% of the patients. The
      improvement in the symptom score, flow rate and residual urine was significantly
      better in patients with marginal obstruction than in patients with unequivocal
      obstruction. CONCLUSION: Urodynamic analysis can predict the treatment outcome of
      TUMT and the results of thermotherapy are significantly better in patients with
      marginal prostatic bladder outflow obstruction.

PMID- 8881949
TI  - A comparative study of laser ablation and transurethral electroresection for
      benign prostatic hyperplasia: results of a 6-month follow-up.
AB  - OBJECTIVE: To compare the efficacy of standard transurethral electroresection of
      the prostate (TURP) and visual laser ablation in the treatment of benign
      prostatic hyperplasia (BPH). PATIENTS AND METHODS: In a randomized prospective
      study, the prostate glands of 60 patients with symptomatic bladder outlet
      obstruction caused by BPH were treated with TURP or visual ablation with the
      Ultraline side-firing Nd:YAG laser; the patients were assessed using standard
      symptom scores, the measurement of residual urine and uroflowmetry both before
      and at 3 and 6 months after treatment. RESULTS: All patients in both treatment
      groups had a significant improvement in symptoms and objective measures of
      voiding. The laser treatment gave significantly better improvements in symptom
      score than did TURP (P = 0.034), but TURP produced significantly better peak
      urinary flow rates (P = 0.025). CONCLUSION: These early results indicate that
      laser ablation of BPH may be a good alternative in the surgical treatment of this
      disease.

PMID- 8881950
TI  - Identification of patients requiring out-patient follow-up after transurethral
      prostatectomy: is there a role for nurse-led screening of post-operative outcomes
      by telephone?
AB  - OBJECTIVE: To determine the most efficient method to follow patients after
      transurethral prostatectomy (TURP) such that only those patients suffering
      significant post-operative problems are reviewed. PATIENTS AND METHODS: The study
      comprised two parts: (1) a retrospective review of the case notes of 100
      consecutive patients who underwent TURP under one consultant to determine whether
      any factors could be identified pre- or post-operatively by which those patients
      most likely to require clinic review could be selected and; (2) a prospective
      review of the succeeding 100 patients undergoing TURP, using a telephone
      'screening' call made by the urological research nurse 3 months after the
      operation. Patients who requested follow-up and those patients with malignancy or
      admitted in high-pressure chronic retention were reviewed in the out-patient
      department. RESULTS: In the first part, 17 patients (17%) required an out-patient
      review for malignancy. Only nine patients (11%) with benign histology required
      further treatment after TURP; this subgroup could not be identified on the basis
      of their pre- or post-operative symptoms. In the second part, 23 patients were
      not reviewed by telephone; 14 had carcinoma of the prostate, eight had no
      telephone and one could not be contacted after seven attempts. Of the remaining
      77 contacted by phone, 61 (79%) declined further clinic review and 16 (21%)
      requested follow-up for persistent problems. A mean of two calls was made per
      patient and the mean duration of each call was 6.3 min. CONCLUSIONS: Based on pre
      or post-operative symptoms at the time of discharge, there is no reliable method
      of identifying those patients who have a poor result after TURP. Telephone
      screening of patients at 3 months identified successfully those patients who
      required an out-patient review and enabled resources to be targeted towards this
      difficult group of patients.

PMID- 8881951
TI  - Effect of finasteride on free and total serum prostate-specific antigen in men
      with benign prostatic hyperplasia.
AB  - OBJECTIVE: To examine changes in the free-to-total (f/t) serum prostate-specific
      antigen (PSA) ratio among men treated with finasteride for benign prostatic
      hypertrophy. PATIENTS AND METHODS: Blood samples were taken from 20 men (mean age
      71 years, range 61-87) before and after a minimum of 9 months of treatment with
      finasteride and the f/tPSA ratio determined using the Immulite assay system.
      RESULTS: Although mean total and free PSA levels decreased significantly, the
      mean f/tPSA ratio increased only slightly and not significantly; the ratios
      remained unchanged in men with an initially low or high (< > 10%) ratio.
      CONCLUSIONS: Concern has been expressed over the loss of the discriminatory power
      of serum PSA in a patient receiving treatment with finasteride. The f/tPSA ratio,
      currently used to help differentiate benign from malignant processes in the
      prostate, remains valid during treatment with finasteride; it does not affect the
      f/tPSA ratio.

PMID- 8881952
TI  - Free-to-total prostate-specific antigen serum concentrations in patients with
      prostate cancer and benign prostatic hyperplasia.
AB  - OBJECTIVE: To determine whether the proportion of total serum prostate-specific
      antigen (tPSA) which is unbound or free (free PSA) offers a better discriminant
      for the detection of patients with prostate cancer (CaP) and those with benign
      prostatic hyperplasia (BPH) than does serum tPSA alone. PATIENTS AND METHODS: In
      a retrospective analysis, the proportion of free PSA was determined in the sera
      of 60 patients with histologically confirmed localized (n = 39; pT1-3NoMo) and
      metastatic (n = 21; T2-4NxM+) CaP and 45 patients with BPH. Forty patients with
      urolithiasis served as a control group. Serum levels of free and total PSA were
      determined using a chemiluminescent enzyme immunoassay. RESULTS: Patients with
      CaP had a lower percentage of free PSA (localized CaP median 8.8%; metastatic CaP
      median 7.1%) than patients with BPH (median 19.5%) and those with urolithiasis
      (median 18.8%: P < 0.001). The percentage of free PSA did not differ
      significantly between patients with clinically localized and metastatic disease.
      CONCLUSION: The determination of the proportion of free PSA enhanced the
      discrimination between BPH and CaP and may reduce the number of unnecessary
      biopsies in patients with an elevated PSA. The results warrant further
      investigations in a broader population to improve the clinical use of serum PSA
      as a tumour marker for discriminating patients with an early, potentially curable
      CaP from men with BPH.

PMID- 8881953
TI  - Abnormal prostatic cells in ejaculates from men with prostatic cancer--a
      preliminary report.
AB  - OBJECTIVE: To relate findings from a novel approach, ejaculate cytology, to the
      established reference, histopathology from transrectal ultrasonography (TRUS)
      guided prostatic biopsies, in patients at risk of having prostatic cancer on the
      basis of an abnormal digital rectal examination (DRE) and/or an elevated serum
      prostate specific antigen (PSA). PATIENTS SUBJECTS AND METHODS: Thirty-seven men
      suspected of having prostatic carcinoma provided ejaculate specimens which were
      collected in Hanks solution. The specimens were centrifuged to form a pellet from
      which smears were made for cytological examination. Immunohistochemical staining
      for PSA and prostatic acid phosphatase (PAP) were performed on embedded blocks of
      these cells. TRUS-guided sextant biopsies were performed for histological
      specimens using standard clinical procedures. A control group of 32 men < 30
      years of age, with no family history of prostatic cancer, also produced specimens
      of ejaculate which were processed similarly. RESULTS: Frankly malignant and
      atypical prostatic cells were identified in ejaculate specimens from 14 of the 37
      patients. Of 12 patients with TRUS biopsies positive for malignancy, nine (75%)
      had abnormal cells in their ejaculates. Furthermore, five of 25 patients with
      negative biopsies for adenocarcinoma also had abnormal ejaculate cytology; two of
      these five patients had high-grade prostatic intra-epithelial neoplasia (PIN). In
      the control group, no PSA- or PAP-positive prostatic epithelial cells were
      identified. Normal prostatic cells were not seen in any of the ejaculate
      specimens examined. CONCLUSIONS: These results indicate that ejaculate cytology,
      which is a non-invasive and easily repeated investigation, may prove to be a
      useful approach in the early detection of cancer of the prostate. However, its
      value in this role, together with the clinical significance of cytological
      findings, needs to be established, especially in relation to PSA and TRUS biopsy.

PMID- 8881954
TI  - The role of digital rectal examination, biopsy Gleason sum and prostate-specific
      antigen in selecting patients who require pelvic lymph node dissections for
      prostate cancer.
AB  - OBJECTIVE: To examine the usefulness of clinical stage, tumour differentiation
      and prostate-specific antigen (PSA) level, alone and in combination, to predict
      regional nodal metastases in individual patients with localized prostate cancer.
      PATIENTS AND METHODS: The usefulness of digital rectal examination (DRE), biopsy
      Gleason sum and PSA, alone and in combination, to predict nodal metastases in an
      individual patient was examined. The study included 689 patients who had
      laparoscopic or open pelvic lymph node dissection for clinical stage T1-3
      prostate cancer. The Kruskal-Wallis test, Mantel-Haenszel test, chi-squared test
      and logistic regression were used for continuous, ordinal, categorical, and
      multivariate analysis, respectively. RESULTS: Of the 689 patients who underwent
      radical prostatectomy, 52 (8%) had nodal metastases. Although clinical stage,
      DRE, pre-operative PSA level and biopsy Gleason sum were significantly related in
      the univariate analysis, only pre-operative PSA level and biopsy Gleason sum were
      significant predictors of lymph node status in a multivariate analysis. However,
      based on a receiver operating characteristic curve, a model with satisfactory
      sensitivity and specificity could not be obtained. CONCLUSION: Current
      estimations of primary prostate cancer biology using pre-operative PSA level,
      clinical stage and biopsy Gleason sum are not sufficiently sensitive to predict
      nodal metastases, and pelvic lymphadenectomy remains the definitive method of
      detection.

PMID- 8881955
TI  - The proportional decrease in prostate specific antigen level best predicts the
      duration of survival after hormonal therapy in patients with metastatic carcinoma
      of the prostate.
AB  - OBJECTIVE: To examine the usefulness of a test for prostate specific antigen
      (PSA) to predict survival in hormonally treated patients with metastatic prostate
      cancer. PATIENTS AND METHODS: The study comprised 49 patients (mean age 72 years,
      SD 6) who underwent orchidectomy for metastatic prostate cancer. PSA was measured
      before orchidectomy and after 6 months, and the absolute, differential and
      proportional decreases calculated. A Cox proportional hazards regression model,
      which controlled for patient age, tumour (Gleason) grade and the number of
      skeletal metastases, was then used to evaluate these estimates of PSA as
      predictors of survival. RESULTS: The 6-month proportional decrease in PSA from
      the pre-operative level was the most accurate predictor of patient survival (P =
      0.006) after hormonal therapy for metastatic prostate cancer. CONCLUSION: This
      information may help to direct appropriate patients to new and experimental
      therapies for metastatic disease.

PMID- 8881956
TI  - A 3-year follow-up of patients with localized prostate cancer operated on with or
      without pre-treatment with the GnRH-agonist triptorelin.
AB  - OBJECTIVE: To examine the effect of pre-operative androgen deprivation on the
      progression rate of malignancy in patients operated on for localized prostate
      cancer. PATIENTS AND METHODS: A total of 53 patients received no hormone therapy
      (group 1) and a further 38 patients (group 2) received the generic releasing
      hormone agonist triptorelin during the 3 months before surgery. The patients in
      group 1 had T1b-T2 tumours, whereas 12 of those in group 2 had clinical stage T3
      tumours. Despite this, the surgical specimens from the patients in group 2 showed
      a rate of cancer invasion of the surgical margins 20% lower than those from the
      patients in group 1. After prostatectomy, the patients were followed for 3 years
      by repeated analyses of prostate-specific antigen (PSA) in serum. RESULTS: During
      the follow-up, the PSA level exceeded the upper threshold (0.6 ng/mL) in 16% of
      the patients in group 1 and in 43% of those in group 2 (P < 0.05). This
      difference was mainly related to the pre-treatment stage of the tumor. Some of
      the patients in group 1 received post-operative radiotherapy but this was not
      reflected in their PSA levels. Of the patients in group 1 and 2, 4% and 14%
      respectively (P > 0.05), developed symptoms from skeletal metastases. CONCLUSION:
      There was no evidence that pre-operative hormone therapy slowed the progression
      of prostate cancer.

PMID- 8881957
TI  - Open versus closed epididymal sperm retrieval in men with secondarily obstructed
      vasal systems--a preliminary report.
AB  - OBJECTIVE: To evaluate and compare sperm quality and suitability for
      intracytoplasmic sperm injection (ICSI) from open and percutaneous epididymal
      aspiration in men with obstructive azoospermia, and to determine the relevance of
      epididymal morphology. PATIENTS AND METHODS: A series of 20 men undergoing
      vasectomy reversal were evaluated by percutaneous (PESA) and open epididymal
      sperm aspiration (MESA) before undergoing surgery for reversal. Two samples were
      taken with PESA, one with the needle in situ (PESA1) and the second while
      withdrawing the needle (PESA2). Epididymal morphology was graded as normal,
      distended and grossly distended. Five men undergoing vasectomy served as a
      control, nonobstructed group for percutaneous aspiration. Analysis of the
      aspirates was performed immediately after operation with no knowledge of the
      treatment, and aspiration was considered successful if sperm suitable for ICSI
      were retrieved. RESULTS: In the obstructed group, 15 of 20 men had successful
      PESA and 13 of these also had successful MESA. PESA was successful bilaterally
      eight times compared with MESA on five occasions; two men with successful PESA
      had no success with MESA. PESA2 was five times more successful than PESA1. Only
      one PESA in the non-obstructed group was suitable for ICSI. PESA was successful
      in 21 of 25 distended or grossly distended epididymi compared with only three of
      21 non-distended systems. CONCLUSION: PESA is a viable alternative to MESA in
      patients with obstructive azoospermia, particularly when associated with
      clinically distended epididymi.

PMID- 8881959
TI  - Genitourinary tract injuries in girls.
AB  - OBJECTIVE: To evaluate lower genitourinary tract injuries in girls and to propose
      guidelines for the investigation and initial management of this unusual injury.
      PATIENTS AND METHODS: The hospital records of 38 girls (aged 2-13 years) treated
      in our institution because of lower genitourinary (LG) tract injury between 1988
      and 1995 were reviewed retrospectively. Urethral ruptures were detected in six
      patients, but the most frequent injuries were to the vulva (63%) and vagina
      (53%). There were pelvic fractures in eight patients and femoral fractures in a
      further five. Eight patients had concomitant anorectal lacerations. Vaginal and
      perineal lacerations were repaired primarily and a temporary urethral catheter
      was placed for a mean of 3 days. Partial urethral disruptions were repaired
      primarily over a stenting catheter in three patients. In one case, vaginal
      laceration and proximal complete rupture of the urethra was managed through a
      transvaginal approach with end-to-end urethral anastomosis over a stenting
      catheter. There was a complete rupture of the distal urethra and avulsion of the
      external meatus in two cases and these patients were managed by urethral
      advancement and meatoplasty. RESULTS: Perineal physical signs did not reflect the
      severity of the lesions and cystovaginoscopy allowed localization of lacerations
      in some cases. Primary repair was possible in all cases. Three patients (8%) had
      wound infection after surgery. One patient had temporary urinary incontinence
      which was managed conservatively and one patient had faecal incontinence which
      needed secondary surgery. CONCLUSION: All female paediatric patients with
      suspected LG tract injury should undergo examination under anaesthesia to
      determine the degree of injury or possible concomitant injury to the urethra,
      bladder or rectum. Primary repair of these injuries is recommended.

PMID- 8881958
TI  - The influence of temperature on changes in pH, lactate and morphology during
      testicular ischaemia.
AB  - OBJECTIVE: To examine the role of temperature in the irreversible changes that
      occur within 4-6 h as ischaemic atrophy develops in the testis during testicular
      torsion, by determining effects on testicular pH, lactate accumulation and
      morphology. MATERIALS AND METHODS: Tissue acidification (pH), tissue lactate and
      structural changes were measured at temperatures of 35, 25, 15 and 5 degrees C in
      34 human testes obtained as orchidectomy specimens from patients with metastatic
      prostatic cancer, and in 19 testes taken from young dogs. RESULTS: At a normal
      testicular temperature of 35 degrees C, the pH decreased to 6.0 within 2 h of the
      onset of ischaemia; cooling to 15 degrees C extended this delay to 6 h. Tissue
      lactate increased from 25 mumol/g dry weight to about 200 mumol/g at 35 degrees
      C. Semi-thin sections of the canine testes showed swelling of the intratubular
      tissue with loss of interstitial space; lower temperature delayed these changes.
      CONCLUSIONS: In the present study, 6 h of torsion was relatively prolonged, in
      that the pH decreased to 5.8 and testicular tissue was destroyed. Acidification
      and histological damage can be prevented by cooling. The critical pH of the
      testis beyond which irreversible changes occur is unknown; a pH of < 6.0 is
      likely to provoke such changes.

PMID- 8881960
TI  - Urethral injury in girls with fractured pelvis following blunt abdominal trauma.
AB  - OBJECTIVE: To review the management of major urethral injury in three girls with
      fractured pelvis following blunt abdominal trauma. PATIENTS AND METHODS: Three
      girls aged 5 years, 1 year and 3 years sustained major urethral injury in
      association with fractured pelvis following blunt abdominal trauma. Initial
      management was undertaken elsewhere. Two girls, with complete loss of the urethra
      and a closed bladder base, were managed by construction of a neourethra using a
      flipped anterior bladder-wall tube. The third patient with extensive perineal
      soft-tissue loss and rupture of the bladder neck and urethra had a modified Young
      Dees-Leadbetter bladder neck reconstruction. All three had an associated vaginal
      injury which did not require a specific surgical procedure. RESULTS: The two
      girls who underwent construction of a neourethra using a flipped anterior bladder
      wall tube are continent. The first voids normally and the second is managed by
      clean intermittent catheterization. The patient who underwent bladder neck
      reconstruction is incontinent and further surgery, possibly a continent
      diversion, may be necessary. CONCLUSION: Pelvic fracture following blunt
      abdominal trauma in girls may be associated with major urethral injury, usually
      with an associated vaginal injury. Surgical ingenuity is required to repair such
      injuries successfully. In those with complete loss of the urethra, a flipped
      anterior bladder-wall tube neourethra is suitable.

PMID- 8881961
TI  - The origin of vesico-ureteric reflux in male newborns: further evidence in favour
      of a transient fetal urethral obstruction.
AB  - OBJECTIVE: To present further arguments supporting a transient urethral
      obstruction occurring during early fetal development as an explanation of the
      origin of vesico-ureteric reflux (VUR) in baby boys. PATIENTS AND METHODS: The
      findings of ultrasonography and voiding cysto-urethrography (VCUG) in 25 baby
      boys with VUR were reviewed, studying mainly bladder and urethral anomalies on
      VCUG and bladder-wall thickness on ultrasonography. RESULTS: A bladder or
      urethral anomaly was found in 15 patients, comprising isolated posterior urethral
      dilatation in five, posterior urethral dilatation with a bladder anomaly in four,
      tubular appearance of the urethra in two and bladder neck hypercontractility with
      diverticulae in four. Bladder-wall thickness ranged from 1 to 8 mm (mean 3.7) and
      in eight patients, the thickness exceeded 5 mm. CONCLUSION: The bladder and
      urethral anomalies found in this series of patients with neonatal VUR could be
      explained by a transient bladder outlet obstruction that possibly occurred in
      utero. These findings support the theory that a significant number of cases of
      VUR seen in baby boys result from a transient fetal urethral obstruction.

PMID- 8881962
TI  - Stone matrix clearance from the pelvicalyceal system using a bottle-brush.

PMID- 8881963
TI  - Easing the technical difficulty of microscopic vasectomy reversal.

PMID- 8881964
TI  - Actinomycosis associated with pilonidal sinus of the penis.

PMID- 8881966
TI  - An unusual prostatic foreign body.

PMID- 8881965
TI  - Adenocarcinoma of the residual bladder following caecocystoplasty for
      cyclophosphamide-induced cystitis.

PMID- 8881967
TI  - Multiple neurilemmomas of the penis.

PMID- 8881968
TI  - Neurilemmoma of the kidney.

PMID- 8881969
TI  - Trousseau's syndrome in renal cell carcinoma.

PMID- 8881970
TI  - Liposuction for retracted urostomy.

PMID- 8881972
TI  - Late conduit perforation in a modified classical Mitrofanoff continent urinary
      diversion.

PMID- 8881971
TI  - A reno-colonic fistula associated with adult polycystic kidney disease.

PMID- 8881973
TI  - Peri-arteritis causing ureteric obstruction.

PMID- 8881974
TI  - Xanthogranulomatous pyelonephritis presenting as a psoas abscess in a child.

PMID- 8881975
TI  - A simple method for checking ureteric JJ stent position.

PMID- 8881976
TI  - Sexual function after radiotherapy treatment for prostate cancer.

PMID- 8881977
TI  - Fibre-optic cystoscope-guided insertion of J-J ureteric stent.

PMID- 8881978
TI  - Staging problems in the pre-operative chemotherapy of Wilms' tumour.

PMID- 8881979
TI  - Management of ureteric calculi during pregnancy by ureteroscopy and laser
      lithotripsy.

PMID- 8881980
TI  - The management of cerebral palsy: subjectivity and a conundrum.

PMID- 8881981
TI  - Baclofen in the treatment of cerebral palsy.
AB  - Baclofen, a gamma-aminobutyric acid agonist, acts at the spinal cord level to
      impede the release of excitatory neurotransmitters that cause spasticity. Oral
      baclofen improves cerebral spasticity mildly, but its activity is limited because
      of its poor lipid solubility. Cerebrospinal fluid baclofen levels after
      intrathecal administration are many times higher than those achieved after oral
      administration. Continuous intrathecal baclofen infusion has been used to treat
      cerebral spasticity in two patient groups: in older ambulatory children with
      inadequate underlying leg strength, and in patients with severe spasticity in
      both the upper and lower extremities. Responsiveness to intrathecal baclofen is
      confirmed by test injections before insertion of a programmable subcutaneous
      pump. Continuous intrathecal baclofen infusion dosages vary from 27 to 800
      micrograms/day. Continuous intrathecal baclofen infusion reduces spasticity in
      the upper and lower extremities, and improves upper extremity function and
      activities of daily living but has no effect on athetosis in the dosages used to
      treat spasticity. Complications related to the intrathecal catheter occur in
      approximately 20% of patients, and infection requiring pump removal occurs in
      approximately 5%. Preliminary studies indicate that continuous intrathecal
      baclofen infusion alleviates some forms of generalized dystonia associated with
      cerebral palsy.

PMID- 8881982
TI  - Neurologic abnormalities in infantile autism.
AB  - Neuroanatomic, pathologic, and neurobehavioral studies point to a cerebellar and
      parietal abnormality in autism. We used a standardized protocol to examine
      neurologic function in 28 pediatric autistic subjects and 24 pediatric normal
      healthy volunteer controls. As a group, the autistic subjects had quantitative
      measures from magnetic resonance imaging suggesting hypoplasia or hyperplasia of
      the cerebellar vermis, as well as measurements of posterior corpus callosum
      suggesting abnormalities of posterior cortex. In groups of tests that reflect
      cerebellar and parietal function, the neurologic abnormalities detectable by
      clinical examination were significantly greater for autistic subjects than for
      normal controls. These studies confirm that the structural and behavioral deficit
      in autism does lead to abnormalities that can be detected on the clinical
      neurologic examination.

PMID- 8881983
TI  - Predictors of clonidine response in Tourette syndrome: implications and
      inferences.
AB  - Clonidine is an alpha-adrenergic agonist which may alleviate emerging symptoms in
      Tourette syndrome, an observation that has fueled speculation regarding
      involvement of stress-sensitive central noradrenergic systems in this disorder.
      We conducted a retrospective study of 53 juvenile patients with Tourette syndrome
      to assess predictors of short-term behavioral and tic response to oral clonidine
      and to examine the relationship, if any, among pretreatment blood pressure, tic
      severity, and clonidine response. When adverse effects were considered, older
      subjects experienced a better therapeutic response to clonidine, independent of
      dose. Improvement in symptoms of attention-deficit hyperactivity disorder was
      associated with a longer duration of vocal tics before treatment. Baseline
      sitting diastolic blood pressure was directly correlated with measures of tic
      severity but not with tic response to clonidine. The findings (1) provide
      indirect support for involvement of central noradrenergic systems in tic
      expression; (2) suggest that emergence of a tic-related neurophysiologic
      dysfunction may be necessary for optimal behavioral response to clonidine in
      Tourette syndrome; and (3) provide broad guidelines for the clinician considering
      clonidine therapy for pediatric patients with Tourette syndrome, particularly
      those with comorbid attention-deficit hyperactivity disorder.

PMID- 8881984
TI  - Apnea of infancy, seizures, and gastroesophageal reflux: an important but
      infrequent association.
AB  - Seventeen infants between 3 and 37 weeks of age were sequentially admitted for
      investigation of apnea of infancy or apparent life-threatening events associated
      with suspected regurgitation. They all underwent an overnight polygraphic study,
      including esophageal pH monitoring. In nine infants, gastroesophageal reflux was
      diagnosed. In five of them, the reflux was associated with apnea. However,
      unassociated episodes of apnea and gastroesophageal reflux occurred (7.1 times
      and four times, respectively) more frequently than associated episodes. In two of
      the five infants, a seizure preceded both reflux and apnea and might have acted
      as a trigger for the apparent life-threatening events. Infants with apparent life
      threatening events or apnea of infancy frequently demonstrate gastroesophageal
      reflux that cannot be consistently related to their events. However, when the
      association is demonstrated, a common epileptic convulsive etiology should be
      considered.

PMID- 8881985
TI  - Increased ALZ-50 immunoreactivity in sudden infant death syndrome.
AB  - Neuronal expression of the ALZ-50 epitope was investigated in hippocampus and
      medulla from infants dying of sudden infant death syndrome or known causes
      (controls). Hippocampal studies include data from 31 infants dying of known
      causes between 32 weeks' gestation and 16 months postpartum and 46 infants who
      died of sudden infant death syndrome. The medulla at the level of the mid olivary
      protuberance was investigated in 22 infants with sudden infant death syndrome and
      11 controls matched for age and postmortem interval. Medullary sections were also
      examined using immunohistochemical methods to demonstrate reactivity to glial
      fibrillary acidic protein antibody. The density of ALZ-50-immunodecorated neurons
      in control hippocampus rises from the level observable in utero to a maximum
      between 1 and 4 months of age and declines thereafter. The density of ALZ-50
      immunoreactive neurons in hippocampus is significantly increased in infants with
      sudden infant death syndrome at all ages. Significant regionally specific
      increases in the number of ALZ-50-immunoreactive neurons, and glial fibrillary
      acidic protein-reactive cells were found in sudden infant death syndrome medulla;
      coincidental increases were observed in only the solitary nucleus. Neurons
      exhibiting the ALZ-50 epitope may reflect apoptotic neuron death of normal
      development, and increased numbers of immunoreactive neurons may suggest enhanced
      neurodegeneration in sudden infant death syndrome.

PMID- 8881986
TI  - Leber's congenital amaurosis associated with mitochondrial dysfunction.
AB  - We report the case histories of two 6-month-old girls, both with young,
      nonconsanguineous parents, referred to us for suspected blindness. In both cases,
      Leber's congenital amaurosis was diagnosed. Due to persistently high lactic acid
      levels in blood, muscle biopsies were taken. Analysis of biopsies revealed that
      both patients had low levels of complex IV of the mitochondrial respiratory
      chain; one patient additionally had low levels of complex III. Microscopic and
      ultrastructural alterations of muscle, typically observed in mitochondrial
      disorders, were observed only in the second patient. These observations raise the
      possibility that at least some cases of Leber's congenital amaurosis may be due
      to alterations in the mitochondrial respiratory chain.

PMID- 8881987
TI  - Basal ganglia volumes in children with attention-deficit hyperactivity disorder.
AB  - Previous research has demonstrated volume reduction of the left globus pallidus
      in children with the codiagnoses of Tourette syndrome and attention-deficit
      hyperactivity disorder (ADHD), in comparison with children who have Tourette
      syndrome alone and with normal controls. The purpose of this study was to
      determine whether children with ADHD alone also had volume reduction of the
      globus pallidus or other basal ganglia structures. Subjects were 10 boys with
      ADHD, 16 boys with Tourette syndrome and ADHD, and 11 normal control boys. Groups
      were matched for age. Boys with ADHD were individually matched for age,
      handedness, and IQ to 10 of the 16 boys with Tourette syndrome and ADHD. Volumes
      of caudate, putamen, and globus pallidus were measured and corrected for brain
      volume. The boys with ADHD had significantly smaller left globus pallidus volume
      and total globus pallidus volume (corrected for brain volume) than the normal
      controls. The Tourette syndrome plus ADHD group did not differ from the ADHD
      group on any of the measures. We conclude that small globus pallidus volume,
      particularly on the left side, is associated with ADHD.

PMID- 8881988
TI  - Pediatric ulnar mononeuropathy: report of 21 electromyography-documented cases
      and review of the literature.
AB  - Pediatric ulnar mononeuropathies are the most frequent upper extremity
      mononeuropathies seen in the electromyography laboratory at The Children's
      Hospital, Boston. Twenty-one children (12 boys and nine girls) with pediatric
      ulnar mononeuropathy, aged 5 to 18 years, were seen from 1979 to 1991. The causes
      included acute trauma in 11 children (52%), compression in five children (24%),
      entrapment in three children (14%), and indeterminate in two children (10%). The
      sites of nerve injury included the elbow in 10 children (48%), forearm in three
      children (14%), wrist in five children (24%), hand in one child (4%), and
      indeterminate in the remaining two children (10%). Prognosis is more favorable in
      nontraumatic (83% improved) pediatric ulnar neuropathies than with traumatic
      lesions (56% improved), with at least a 1-year follow-up.

PMID- 8881989
TI  - Respiratory sinus arrhythmia in patients with Prader-Willi syndrome.
AB  - In this investigation, we sought to further test the hypothesis that
      parasympathetic deficiency exists among persons with Prader-Willi syndrome, by
      examining respiratory sinus arrhythmia. The study sample comprised two groups of
      patients: 14 subjects with Prader-Willi syndrome and 14 age- and sex-matched
      controls. Each subject's electrocardiogram was recorded in a quiet room and
      digitized by a personal computer during five 1-minute periods. RR intervals
      within each 1-minute period were converted to heart rate in 120 successive 0.5
      second intervals. The resultant heart rate time series was converted to its
      underlying frequency composition by a fast Fourier transform and averaged across
      minutes. Respiratory sinus arrhythmia was defined as the variability in the time
      series over a frequency range (0.096 to 0.48 Hz) corresponding to a range of
      respiratory rates from six to 30 breaths/minute. Analysis revealed significantly
      less variability in the heart rates of subjects with Prader-Willi syndrome
      relative to age- and sex-matched controls (group x frequency bin: F = 2.26, P <
      .05). An analysis of covariance adjusting for body mass index differences between
      the groups produced identical results. These findings support the existence of a
      parasympathetic deficiency among subjects with Prader-Willi syndrome independent
      of their body mass. This is likely due to dysregulation of the central autonomic
      network.

PMID- 8881990
TI  - Reminiscences of an earlier career.

PMID- 8881991
TI  - Correlation between the histopathologic, genotypic, and phenotypic features of
      hereditary peripheral neuropathies in childhood.
AB  - In recent years, there have been remarkable advances in the understanding of the
      molecular genetic basis of the hereditary polyneuropathies. Linkage of the genes
      for Charcot-Marie-Tooth disease to chromosomes 1 and then 17 was followed by the
      discovery that the commonest form of Charcot-Marie-Tooth disease (CMT1A) was due
      to a duplication of DNA at 17p11.2-12. This duplication was shown to contain the
      gene for peripheral myelin protein PMP22. The finding that mutations of the
      myelin protein PMP22 gene were present in some Charcot-Marie-Tooth disease cases
      lacking the duplication confirmed the myelin protein PMP22 gene as the site of
      the defect in Charcot-Marie-Tooth disease. Similarly, defects of the myelin
      protein P0 gene on chromosome 1 have been demonstrated in a rarer form of Charcot
      Marie-Tooth disease (CMT1B). A deletion of DNA at 17p11.2-12 results in the
      disorder hereditary neuropathy with liability to pressure palsies. Other
      mutations of the myelin protein PMP22 and myelin protein P0 genes have been
      associated with the clinical syndrome known as Dejerine-Sottas disease. An X
      linked form of Charcot-Marie-Tooth disease (CMTX) has been characterized and
      shown to be due to mutations of the gap junction protein, connexin 32. Transgenic
      murine models with inactivated myelin protein PMP22 and myelin protein P0 genes
      have shown pathologic changes strinkingly similar to those seen in human patients
      with disturbances of those genes. In this paper, the clinical and histopathologic
      characteristics of these conditions are discussed in relation to the genotypic
      basis. It will be argued that there is still an important place for the clinician
      and nerve pathologist in a medical world immersed in the wonders of molecular
      genetics.

PMID- 8881992
TI  - Electrophysiologic measures of delayed maturation in attention-deficit
      hyperactivity disorder.

PMID- 8881993
TI  - Volvular epilepsy associated with line-of-migration abnormality: a case report.

PMID- 8881994
TI  - Fatal mumps meningoencephalitis in a child with severe combined immunodeficiency
      after bone marrow transplantation.

PMID- 8881995
TI  - Central apnea in a child with congenital autonomic dysfunction and universal pain
      loss.

PMID- 8881997
TI  - Hemidystonia improved by baclofen and PET scan findings in a patient with
      glutaric aciduria type I.

PMID- 8881996
TI  - Neuromyelitis optica in childhood: case report with sequential MRI findings.

PMID- 8881998
TI  - The use of felbamate to treat infantile spasms.

PMID- 8881999
TI  - Expert witness testimony.

PMID- 8882000
TI  - Studies on the purification of peroxidase from horseradish roots using reverse
      micelles.
AB  - Horseradish peroxidase (HRP) was successfully purified from horseradish roots by
      a two-stage reverse-micellar extraction from the dialyzed aqueous extract. The
      anionic surfactant AOT dissolved in isooctane was used to produce the reverse
      micellar phases. The narrow pH range at which HRP solubilization occurred was
      exploited to remove most of the contaminant proteins in the first forward
      extraction. In the second extraction stage, HRP was selectively solubilized and
      concentrated by using a volume ratio of 10 between the aqueous and organic
      phases. The HRP final specific activity was 86 guaiacol U mg-1, obtained with a
      purification factor of 80 and yield of 46%. Sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis showed two overlapping bands, with HRP corresponding to that
      at 43.8 kDa. Image analysis on isoelectric focusing (IEF) gels showed that the
      HRP was 80% pure. Ion exchange liquid chromatography showed that most of the
      specific activity was due to the basic isoenzyme with pI 8.5, which comprises
      33.5% of the product. There were high HRP losses as a precipitate at the
      interface when direct reverse-micellar extraction was attempted from the crude
      extract. It is believed that the hydrophobic environment near the haem group of
      the HRP basic isoenzyme favors complex formation with the surfactant, and that
      this is promoted at higher protein concentrations.

PMID- 8882001
TI  - Substrate specificity and kinetics of Candida rugosa lipase in organic media.
AB  - The fatty acid specificity of lipase from Candida rugosa during the
      esterification of saturated fatty acids and sulcatol in toluene has been studied.
      The true kinetic parameters are obtained by fitting the experimental data to a
      Ping-Pong kinetic model that includes alcohol inhibition. The fitted parameter
      values are compared with apparent values that would be obtained from restricted
      data sets in which one of the substrate concentrations was kept constant. It has
      been found that in reactions inhibited by alcohol the true Ping-Pong parameters
      can be significantly different from the apparent ones. Corrections for solvation
      are made by using activities instead of concentrations to fit the kinetic
      parameters. Though activity coefficients, estimated using the UNIFAC group
      contribution method, vary by over 25% for changing concentrations in the same
      solvent, their use did not improve the fit to the data. This contrasts with what
      has been found in comparisons of different solvents, where the differences in
      activity coefficients are much larger.

PMID- 8882002
TI  - Development of a gas-phase oxygen biosensor using a blue copper-containing
      oxidase.
AB  - A gas-phase oxygen biosensor based on blue copper-containing oxidases was
      developed. Blue-oxidase enzymes, including laccase and ascorbate oxidase, have a
      blue chromophore prosthetic group, type 1 Cu+2, which can be reduced and
      decolorized with reducing substrates. When the enzyme is reoxidized with
      molecular oxygen, there is a concomitant return of the blue color. The oxygen
      biosensor consisted of the Rhus vernicifera laccase and ascorbate as substrate
      enclosed in pouches of low-density polyethylene under nitrogen gas. Operational
      stability of the biosensor was established by exposing it to different
      oxygen/nitrogen gas mixtures at 5 degrees C. Gas-phase oxygen concentrations were
      measured by keeping it under nitrogen gas and subsequently recording the rate of
      reappearance of the enzyme blue color, both visually and spectrophotometrically
      at 610 nm. The oxygen biosensor was able to detect a wide range of oxygen
      concentrations. The time required to recover the blue color, namely the biosensor
      response time, at the optimized assay conditions of 5 degrees C and a high-water
      activity level, was determined. This research describes the development of an
      oxygen biosensor with adequate activity and stability to measure gas-phase oxygen
      concentrations at 5 degrees C and high-water activity levels. The oxygen
      biosensor could be used to indicate oxygen concentrations above acceptable levels
      in headspace oxygen concentration which could affect the quality and safety of
      products packaged under initial low levels of oxygen concentration.

PMID- 8882003
TI  - Chemoenzymatic synthesis of D(-)phenylglycine using hydantoinase of Pseudomonas
      desmolyticum resting cells.
AB  - We screened 125 Pseudomonas strains from our culture collection for the
      production of hydantoinase activity using DL-phenylhydantoin as a substrate.
      Pseudomonas desmolyticum NCIM 2112 was found to be the best hydantoinase
      (dihydropyrimidinase E.C. 3.5.2.2) producer. The enzymatic reactions were carried
      out using 18-20-h grown cells in nutrient broth and 5-phenylhydantoin as the
      substrate. Optimization studies for the biotransformation reaction were performed
      to increase product yield. The optimum pH and temperature for D(-)N
      carbamoylphenylglycine production were 9.5 and 30 degrees C, respectively.
      Biotransformation under these alkaline conditions allowed the complete conversion
      of 27.0 g l-1 of DL-phenylhydantoin to 26.5 g l-1 of N-carbamoylphenylglycine
      within 24 h, with a molar yield of 90%. The hydantoinase involved in this
      biotransformation process was strictly D-stereospecific, because the product
      isolated was pure D(-)N-carbamoylphenylglycine. This pure product was further
      chemically converted to D(-)phenylglycine using nitrous acid with an 80% chemical
      yield. Thus, the overall conversion efficiency of DL-5-phenylhydantoin to D(
      )phenylglycine was found to be 65-68%.

PMID- 8882004
TI  - Physiologic studies with the sulfate-reducing bacterium Desulfovibrio
      desulfuricans: evaluation for use in a biofuel cell.
AB  - The growth kinetics of the sulfate-reducing bacteria Desulfovibrio desulfuricans
      Essex 6 was investigated under various conditions for potential use in a
      microbial fuel cell that recovers electrons generated from the reduction of
      sulfate to hydrogen sulfide. Hydrogen sulfide was found to inhibit growth and
      decrease both the growth yields and the sulfate-specific reduction rate. Hydrogen
      sulfide inhibition was direct, reversible, and not due to limitation by iron
      deficiency. A high initial lactate concentration also retarded bacterial growth,
      reduced the specific sulfate reduction rates, and gave variable biomass growth
      yields. This effect resulted from a bottleneck in the lactate oxidation pathway
      which induced the production of the secondary product butanol. The use of
      pyruvate as a carbon source was more advantageous than lactate in terms of growth
      rate and biomass growth yields, with only a slight decrease in the rate of
      specific sulfate reduction. For equal biomass, a slightly higher current density
      was generated from lactate than pyruvate, but pyruvate required nearly 40% less
      sulfate.

PMID- 8882005
TI  - Inhibition of D-amino acid oxidase by alpha-keto acids analogs of amino acids.
AB  - The inhibition of D-amino acid oxidase by certain alpha-keto acids products of
      the reaction with D-amino acids, in particular alpha-keto acids that are analogs
      of the amino acids alanine, valine, leucine, phenylanaline, phenylglycine,
      tyrosine and tryptophan, is reported. All the alpha-keto acids assayed behaved as
      substrate competitive inhibitors of the enzyme. The relationship between the
      degree of inhibition and the structure of the inhibitor is discussed.

PMID- 8882006
TI  - Purification and characterization of a glycerol oxidase from Penicillium sp. TS
      622.
AB  - A novel extracellular glycerol oxidase was purified 39-fold from wheat bran
      culture of a soil-isolated Penicillium strain TS-622 with an overall yield of 3%.
      The addition of Triton X-100 into the extraction buffer improved the extraction
      yield by 90 times, indicating that the enzyme is bound to the cell surface. The
      molecular weight of this enzyme was 400,000 as determined by size-exclusion high
      performance liquid chromatography. The optimum pH was from 6 to 7 and the optimum
      temperature was 45 degrees C. This enzyme showed high specificity toward
      dihydroxyacetone and glycerol. It was inhibited by KCN, NaN3, and hydroxylamine.

PMID- 8882007
TI  - Esoteric contact dermatitis. part II: the paraben paradox.

PMID- 8882008
TI  - Scorpion sting reactions.

PMID- 8882009
TI  - Topical retinoic acid (tretinoin) for photoaging: conceptions and misperceptions.

PMID- 8882010
TI  - Tundra tongue.
AB  - When the tongue comes in contact with frozen metal or nonmoist ice cubes, it
      becomes adherent. The author illustrates such an example experienced by his son.

PMID- 8882011
TI  - Subcutaneous mucormycosis seen after gypsum fixation for bone fracture.
AB  - A patient with erythema on the dorsum of the left foot after the removal of
      gypsum fixation applied for the treatment of bone fracture is reported. Both the
      clinical and histopathologic features led to the diagnosis of mucor infection.

PMID- 8882012
TI  - Acquired pili torti--a structural hair shaft defect in anorexia nervosa.
AB  - The hair of seventeen girls aged 13 to 19 years with anorexia nervosa (AN) was
      studied and compared with the hair of fifteen healthy girls aged 13 to 18 years
      with no complaints of hair loss but with similar habits of hairstyling and care.
      Light microscopic examination of the hair revealed no defect in the control
      group. In the AN group, fourteen patients (82.3 percent) had pili torti, an
      acquired hair shaft defect that has not yet been described in association with
      this disease. We estimate that the hair defect was due to malnutrition combined
      with ingestion of exaggerated amounts of yellow vegetables and vitamin
      supplements, causing a significant increase in levels of serum carotene, retinyl
      esters, retinol, and retinoic acid. We suggest a possible link between excess
      vitamin A and pili torti in patients with AN.

PMID- 8882013
TI  - Indurated plaques of mycosis fungoides in a woman with fulminant hepatic failure.
AB  - Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that may mimic, clinically
      and histologically, other more common entities before definitive diagnosis. We
      report a case of plaque-stage MF in a young woman with hepatic failure and
      present an overview of some of the diagnostic features and therapeutic options
      available for this disease.

PMID- 8882014
TI  - An atypical piloleiomyoma presenting as a nonhealing ulcerated nodule.
AB  - Piloleiomyomas are benign smooth muscle tumors arising from the arrectores
      pilorum muscles in the skin. They vary in size and number, and are often
      spontaneously painful or sensitive to touch and cold. An unusual case of an
      ulcerated and painless piloleiomyoma is presented.

PMID- 8882015
TI  - Granuloma annulare-like lesions and secondary hyperparathyroidism.
AB  - We describe a patient with chronic renal disease and secondary
      hyperparathyroidism who developed a lesion of granuloma annulare with evidence of
      calcium in the lesion. The lesion developed after an intravenous infusion of
      calcium gluconate.

PMID- 8882016
TI  - Recurrent lentigo maligna invading a skin graft successfully treated with Mohs'
      micrographic surgery.
AB  - Lentigo maligna (LM) is a pigmented lesion occurring on sun-exposed skin that may
      become lentigo maligna melanoma (LMM). The tumor can behave in an aggressive
      fashion, causing significant cosmetic disfigurement, often extending
      significantly further than the clinical margin. Complete surgical excision is the
      treatment of choice. We describe a 74-year-old woman with a large LM of the left
      cheek, upper and lower eyelids, and preauricular skin that had recurred twice.
      The tumor was removed using Mohs' micrographic surgery (MMS) with rush permanent
      sections and was found to infiltrate extensively the split-thickness skin graft
      that had been placed five years earlier. LM can invade and replace a skin graft.
      Although destructive modalities and conventional surgery are recommended by some
      authors, MMS offers the greatest likelihood of cure, the ability to examine
      nearly 100 percent of the surgical margins, and maximal tissue sparing. Complete
      excision of LM at its earliest recognition may prevent invasive LMM and will
      limit cosmetic disfigurement.

PMID- 8882017
TI  - Primary care and rheumatology in musculoskeletal disorders: bridging the gap.

PMID- 8882018
TI  - OMERED: Outcome measures in rheumatology education.

PMID- 8882019
TI  - Silent myocardial ischemia in Behcet's disease.

PMID- 8882020
TI  - Oral bolus cyclophosphamide--liberating libation or nauseating nostrum?

PMID- 8882021
TI  - Adenosine triphosphate levels in human plasma.
AB  - OBJECTIVE: To quantify extracellular adenosine triphosphate (ATP) levels in human
      platelet-poor plasma as a potential source of synovial fluid ATP, and to
      determine variables affecting these levels. METHODS: ATP was measured by the
      specific luciferase method; platelet beta thromboglobulin was determined by
      radioimmunoassay. The effects of fasting, feeding, venipuncture, and muscular
      exercise were determined by serial venipuncture in healthy subjects. Diurnal
      variation was determined by serial sampling through indwelling venous catheters
      in 3 healthy subjects and 3 women with knee osteoarthritis. RESULTS: Unlike beta
      thromboglobulin levels, which did not change, an invariable marked (mean 58%)
      fall in plasma ATP was noted 15 min after the first venipuncture, whether the
      subject had eaten or not. Indomethacin treatment had no effect on this
      phenomenon. Exercise of forearm muscles had no effect on plasma ATP. The drop in
      plasma ATP occurred between 3 and 15 min, with recovery at about 90 min. A
      diurnal variation in plasma ATP was found with trough levels at noon and at night
      during sleep. CONCLUSION: The predictable sharp fall in plasma ATP levels induced
      by venipuncture and the clear diurnal variation suggest that plasma contains ATP
      independent of platelet dense body release and endothelial cell needle trauma.
      Synovial plasma flow at peak (600 nM) levels is insufficient to provide more than
      one-third of the extracellular ATP needed to generate inorganic pyrophosphate in
      articular tissues.

PMID- 8882022
TI  - Treatment of rheumatoid arthritis by immunization with mononuclear white blood
      cells: results of a preliminary trial.
AB  - OBJECTIVE: To determine if immunization with alloantigenic blood mononuclear
      cells (MNC) in active rheumatoid arthritis (RA) can result in objective and
      subjective improvement in RA. METHODS: Eleven patients meeting American College
      of Rheumatology criteria for RA were treated in an open label trial by
      immunization with allogeneic MNC obtained from donors screened for infectious
      agents according to American Association of Blood Banks guidelines. MNC (30-250 x
      10(6) cells) were given at 6 week intervals. Half the MNC (vol 2 ml) were
      injected intravenously and half in 4 divided doses subcutaneously (sq, 0.5 ml
      each). Disease activity assessments were done before entry and at immunotherapy
      visits thereafter. These included physician global assessment of disease
      activity, patient global assessment of pain, arthritis impact measurement scales
      (AIMS), swollen joint count, erythrocyte sedimentation rate (ESR), and/or C
      reactive protein (CRP). RESULTS: Statistically significant improvement was noted
      in all clinical variables measured when pretreatment data were compared to those
      obtained at the time of injection number 3. MNC dose related improvement was
      found when the total number of cells given in the first 2 injections were
      compared to percentage improvement in patient assessment of pain (r = 0.71, p <
      0.02), AIMS (r = 0.60, p = 0.05), and improvement in the means of all variables
      measured (r = 0.70, p < 0.03). When all variables were averaged, 6 of 11 patients
      experienced > 20% and 3 of 11 experienced > or = 40% improvement. The only side
      effects noted were transient local pain and swelling at the sq injection sites.
      CONCLUSION: MNC immunization may represent a suitable and safe alternative to
      drug treatment for selected patients with RA. Statistically significant
      improvement was found in all variables and several of these were cell dose
      related. A placebo controlled randomized trial immunizing with a standardized
      number of cells will address efficacy of this biological treatment approach.

PMID- 8882023
TI  - Serum phospholipase A2 activity in patients with rheumatoid arthritis before and
      after treatment with methotrexate, auranofin, or combination of the two.
AB  - OBJECTIVE: (1) To confirm a previous observation that serum phospholipase A2
      (PLA2) activity correlates with disease activity in rheumatoid arthritis (RA);
      and (2) to determine whether serum PLA2 activity changes after treatment with
      methotrexate (MTX), auranofin (AF), or a combination of the 2 (COMBO). METHODS:
      Sera obtained at baseline and after treatment from 100 patients with RA (40 MTX,
      32 AF, and 28 COMBO) who participated in a multicenter, double blind trial were
      tested for PLA2 activity using an assay that measures the release of radiolabeled
      14C oleic acid from the cell membrane of Escherichia coli. Detailed statistical
      analysis was performed using previously collected clinical data to determine
      whether correlations exist between RA disease activity and serum PLA2 activity;
      whether baseline serum PLA2 activity predicted a therapeutic response in any
      treatment group; and whether there was a significant change in serum PLA2
      activity after treatment in patients who responded to the various drugs. RESULTS:
      Baseline serum PLA2 activity was significantly increased in patients with RA
      compared to healthy controls. No correlation between serum PLA2 activity and RA
      disease activity was noted at baseline. Mean serum PLA2 activity did not change
      significantly after treatment with MTX, AF, or COMBO in either treatment
      responders or nonresponders. CONCLUSION: Serum PLA2 activity is increased in
      patients with RA compared to healthy controls, but does not correlate with
      disease activity in patients, nor does it predict a response to treatment with
      MTX, AF, or COMBO. Serum PLA2 activity also did not change significantly after
      treatment with any of the above agents.

PMID- 8882024
TI  - Increased nitric oxide levels in patients with rheumatoid arthritis.
AB  - OBJECTIVES: We determined whether serum levels of nitric oxide (NO) correlate
      with disease activity of rheumatoid arthritis (RA) and inflammatory cytokines by
      measuring the serum and synovial fluid (SF) concentrations of NO in patients with
      RA and patients with osteoarthritis (OA) and healthy subjects. METHODS: The
      concentration of NO in each sample was determined by chemiluminescence. Cytokine
      levels were determined using sandwich enzyme-linked immunoassays. RESULTS: The
      mean serum concentration of NO was significantly higher in patients with RA
      (293.4 +/- 108.5 nM) compared with that of patients with OA (33.4 +/- 4.0, p <
      0.01) and healthy subjects (35.9 +/- 4.5, p < 0.01). The mean SF concentration of
      NO (3218 +/- 73.7, p < 0.01) was significantly higher than that of serum in
      patients with RA. Furthermore, levels of serum NO, interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) were significantly higher in patients with RA
      with active disease compared to patients with inactive disease. Serum NO levels
      correlated significantly with the morning joint stiffness, the number of tender
      or swollen joints, and CRP. Furthermore, NO levels correlated significantly with
      serum TNF-alpha and IL-6 levels. CONCLUSIONS: Our results suggest that increased
      endogenous NO synthesis reflects abnormalities of immunoregulation in the joints
      of patients with RA.

PMID- 8882025
TI  - The diagnosis of iron deficiency in patients with rheumatoid arthritis and
      anemia: an algorithm using simple laboratory measures.
AB  - OBJECTIVE: Anemia of chronic disorders (ACD) and iron deficiency are common
      features in rheumatoid arthritis (RA), but may be difficult to distinguish
      without marrow sampling, which is invasive, time consuming, and expensive. We
      sought simple laboratory measures that identified patients with absent marrow
      iron stores (iron deficiency). METHODS: 45 anemic patients with RA underwent
      marrow sampling in addition to a complete blood count and serum ferritin and iron
      saturation measurements. RESULTS: 47% of patients had iron deficiency. These
      patients had significantly lower mean corpuscular volume (MCV), serum ferritin,
      and iron saturation. A 3 step algorithm was developed using these laboratory
      variables to identify iron deficiency. This algorithm correctly classified 94%
      patients with iron deficiency and 85% with ACD. CONCLUSION: Our study
      demonstrates that iron deficiency may be reliably identified by measuring serum
      ferritin, MCV, and iron saturation in many patients with RA, thereby avoiding the
      trauma and expense of marrow sampling.

PMID- 8882026
TI  - Bone alkaline phosphatase in rheumatoid arthritis: a longitudinal study.
AB  - OBJECTIVE: To determine whether the raised total alkaline phosphatase (TAP) found
      in patients with active rheumatoid arthritis (RA) is derived primarily from an
      increase of the bone or liver isoenzyme, and to evaluate the treatment effect of
      steroids and disease modifying antirheumatic drugs (DMARD) on bone alkaline
      phosphatase (BAP) in serial analyses. METHODS: 58 patients with RA were treated
      with the DMARD gold sodium thiomalate (n = 22), D-penicillamine (n = 18), or
      sulfasalazine (n = 18) over a 24 week period with regular assessment of disease
      activity and measurement of BAP using a newly developed specific double
      monoclonal radioimmunometric assay. RESULTS: In the RA group as a whole, BAP
      correlated with TAP at all time points (e.g., Week 0 rs = 0.50, p < 0.0001). In
      contrast, no correlation was found between the intraindividual change of BAP and
      TAP between Weeks 4 and 24. TAP was correlated with disease activity (assessed by
      plasma viscosity rs = 0.33, p < 0.02 for the whole RA group and rs = 0.48, p <
      0.0002 for intraindividual change from Weeks 4 to 24). Similarly, gamma
      glutamyltranspeptidase was correlated with disease activity (rs = 0.56, p <
      0.0001, and rs = 0.50, p < 0.0001, respectively). In contrast, BAP was not
      correlated with disease activity. Low dose steroids and the 3 DMARD studied had
      no significant effect on the time course of BAP. CONCLUSION: In the majority of
      patients with active RA, any increase of TAP is not mirrored by an increase of
      BAP. This supports the hypothesis that inflammatory reactions result in an
      increase in the plasma concentration of the membrane bound enzymes of the
      hepatobiliary system, including gamma-glutamyltranspeptidase and the liver
      isoenzyme of alkaline phosphatase, which is likely to be responsible, at least in
      part, for the increase of TAP. Since BAP is not correlated with disease activity,
      BAP measurements are not useful in monitoring response to treatment.

PMID- 8882027
TI  - Effects of triazolam on sleep, daytime sleepiness, and morning stiffness in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the effects of triazolam upon insomnia and daytime
      sleepiness in patients with rheumatoid arthritis (RA). METHODS: Triazolam or
      placebo was administered during two 7 night periods to 15 patients with RA in a
      double blind crossover study. Polysomnographic recordings were conducted on the
      last 2 nights of each condition, and multiple sleep latency tests and mood and
      arthritis assessments were performed during the intervening day in each
      condition. RESULTS: In the triazolam condition, total sleep time was increased,
      daytime sleepiness was reduced, and morning stiffness was improved compared to
      placebo. Objective measures of sleep fragmentation were unchanged. Clinical
      arthritis assessments were similar during both conditions. CONCLUSION: Short term
      hypnotic therapy improves sleep in patients with RA and appears to improve
      morning stiffness and daytime sleepiness.

PMID- 8882028
TI  - The frequency of cutaneous vasculitis is not increased in patients with
      rheumatoid arthritis treated with methotrexate.
AB  - OBJECTIVE: To analyse the frequency, type, and immunohistological features of
      clinical cutaneous vasculitis developing in patients with rheumatoid arthritis
      (RA) treated or not with methotrexate as well as their demographic, clinical and
      biological characteristics. METHODS: Ninety-one patients with RA receiving 9.5
      mg/wk of methotrexate (MTX) were compared for an average observation time of 18
      months to 130 matched patients with RA treated with various drugs excluding MTX.
      RESULTS: Whether receiving MTX or not, 5.4% of patients with RA developed a
      clinical cutaneous vasculitis. There were significant differences between both
      groups for 2 variables only: a higher percentage of polyneuropathies and a higher
      level of immune complex-plasma levels in non-MTX patients. The immunohistological
      analysis did not differentiate both groups. CONCLUSION: The percentage of
      cutaneous vasculitis that developed under MTX therapy was not different from that
      occurring as a natural complication of longstanding severe RA.

PMID- 8882029
TI  - Diminished autonomic nervous system responsiveness in rheumatoid arthritis of
      recent onset.
AB  - OBJECTIVE: To investigate responsiveness of the autonomic nervous system in
      rheumatoid arthritis (RA) of recent onset. METHODS: 21 patients (17 women, mean
      age 55.7 years) and 20 healthy controls (16 women, mean age 52.7 years) were
      subjected to 4 tasks eliciting divergent autonomic reactions: film watching, mild
      physical exercise, cognitive discrimination, and the Stroop color-word
      interference test. Changes in heart rate, diastolic (DBP) and systolic (SBP)
      blood pressure, and skin conductance relative to pretask baseline values were
      computed and related to erythrocyte sedimentation rate, pain, mobility, and
      dexterity. RESULTS: Mean autonomic levels of patients were normal, as well as
      autonomic responses to film watching and mild physical exercise. Diminished
      autonomic responses were observed during cognitive discrimination and during the
      Stroop test. Blood pressure responses were negatively related to pain severity,
      but positively to impaired dexterity. CONCLUSION: Diminished autonomic nervous
      system response is observed in RA of recent onset, most clearly in patients with
      more severe pain. This suggests that it is associated with primary
      pathophysiological mechanisms.

PMID- 8882030
TI  - Quantitative measurement of erosion growth and joint space loss in rheumatoid
      arthritis hand radiographs.
AB  - OBJECTIVE: To evaluate the performance of simple, inexpensive quantitative
      techniques for measuring erosion growth and joint space loss in serial hand
      radiographs of patients with rheumatoid arthritis (RA). METHODS: Erosions were
      measured using a plastic overlay template of sample erosion sizes. Joint spaces
      were measured with a hand held measuring micrometer. In the first phase of
      testing, a spectrum of individual erosions and joint spaces was measured to
      determine intra and interobserver correlations and variability. In the 2nd phase,
      the tools were used to measure serial changes in RA hand radiographs. Observer
      correlations and the ability to discriminate serial changes were determined and
      compared to the scoring method of Sharp. RESULTS: Measurements of individual
      erosion areas and joint spaces were highly reproducible. Intra and interobserver
      correlations were significant (p < 0.05) for serial erosion growth and joint
      space loss measurements, as well as changes in Sharp scores. Quantitative
      measurements correlated highly with the corresponding Sharp score changes. Of all
      measurements or scores recorded, quantitative joint space loss measurements were
      statistically superior in discriminating serial change in RA hand radiographs.
      Quantitatively measured joint space loss correlated well with both erosion growth
      measurements and serial change in total Sharp scores. CONCLUSION: Quantitative
      measurement of erosion growth and joint space loss is possible with simple
      inexpensive techniques. Further study is needed to confirm our data, which
      suggest that quantitative measurement of joint space narrowing may be the most
      useful discriminator of serial changes in RA hand radiographs.

PMID- 8882031
TI  - Outpatient monthly oral bolus cyclophosphamide therapy in systemic lupus
      erythematosus.
AB  - OBJECTIVE: An open label study to determine the feasibility and acute toxicity of
      a 6 month course of outpatient intermittent bolus high dose oral cyclophosphamide
      in patients with active systemic lupus erythematosus (SLE). METHODS: Oral
      cyclophosphamide in a single dose of 0.5 to 1.0 g/m2 was given monthly for 6
      consecutive months. Disease activity was monitored by quantitative assessments of
      urine sediment, 24h urine protein excretion, and the Systemic Lupus Activity
      Measure (SLAM). RESULTS: Twelve patients (11 with glomerulonephritis and one with
      thrombocytopenia) were studied. Improvements in SLAM scores, proteinuria, and
      urinary cellular casts were observed in the majority of the 9 patients with
      nephritis who completed the study. Adverse effects included mild nausea in most
      patients and intercurrent infections in 2 patients (herpes zoster, cellulitis,
      urinary tract infection). Three patients failed to complete the 6 month course of
      therapy because of treatment failure in the patient with thrombocytopenia,
      pregnancy, and severe vomiting, respectively. CONCLUSION: High dose pulse oral
      cyclophosphamide is an acceptable alternative for the aggressive outpatient
      management of selected patients with lupus nephritis.

PMID- 8882032
TI  - Anti-(DNA-histone) antibodies in active lupus nephritis.
AB  - OBJECTIVE: To detect and characterize anti-(DNA-histone) antibodies in patients
      with active lupus nephritis. METHODS: Calf thymus double stranded DNA was
      reassociated with histone in vitro. Polynucleosomes were prepared from chicken
      erythrocyte nuclei, calf thymus nucleohistone, and human peripheral blood
      mononuclear cells. Anti-DNA activity was depleted from purified IgG using DNA
      cellulose. Binding of the adsorbed IgG to various (DNA-histone) related antigens
      was measured by ELISA. Antigen specificity was assessed by inhibition assays and
      adsorption studies using histone and nucleosome conjugated sepharose beads.
      RESULTS: Anti-(DNA-histone) antibodies were detected in 3 of 5 patients with
      active lupus nephritis. They specifically recognized determinants consisting of
      both DNA and histone, but not DNA or histone alone. Anti-(DNA-histone) antibodies
      largely overlapped with antinucleosome antibodies and appeared to react with
      nucleosomes released by apoptotic human mononuclear cells. CONCLUSION: Anti-(DNA
      histone) antibodies are present in active lupus nephritis and largely represent
      antinucleosome antibodies. They may contribute to the pathogenesis of nephritis
      by forming immune complexes with apoptosis related nucleosomes.

PMID- 8882033
TI  - High prevalence of antiphospholipid antibodies in precapillary pulmonary
      hypertension.
AB  - OBJECTIVE: To assess prevalence and clinical associations of various
      antiphospholipid antibodies (aPL) in patients with primary and secondary
      pulmonary hypertension. METHODS: A prospective trial of aPL in 38 consecutive
      patients with pulmonary hypertension. Nine patients had primary pulmonary
      hypertension. Twenty-nine patients had pulmonary hypertension secondary to
      different etiologies: left heart failure, 8; congenital heart defect, 11; various
      lung diseases, 10. The search for aPL directed against 4 phospholipids
      (cardiolipin, phosphatidylserine, inositol, ethanolamine) was by ELISA. RESULTS:
      Eleven patients (29%) had aPL, with various phospholipid specificities. Mean
      pulmonary artery pressure and mean pulmonary vascular resistance of aPL positive
      patients were not different from those of aPL negative patients. Mean pulmonary
      wedge pressure was significantly lower in aPL positive patients than those
      without aPL. Positive aPL were detected only in patients with precapillary
      pulmonary hypertension (11/30; 36.6%). The prevalence of aPL in primary (4/9;
      44%) was not significantly different from aPL in secondary (7/29; 24%) pulmonary
      hypertension. There was no association between the presence of aPL and prior
      thrombosis or recurrent fetal losses. CONCLUSION: The frequent positivity of aPL
      in precapillary pulmonary hypertension, irrespective of its cause and severity,
      suggests the existence of an associated endothelial disease. These antibodies
      might play a role in the initiation and/or progression of in situ thromboses
      frequently observed in precapillary pulmonary hypertension. Our results reinforce
      the necessity of longterm anticoagulant treatment in these patients.

PMID- 8882034
TI  - Peripheral blood mononuclear cells of patients with systemic sclerosis produce
      increased amounts of interleukin 6, but not transforming growth factor beta 1.
AB  - OBJECTIVE: To assess the ability of peripheral blood mononuclear cells (PBMC) of
      patients with systemic sclerosis (SSc) to produce interleukin 6 (IL-6),
      transforming growth factor beta 1 (TGF-beta 1), to identify the IL-6 producer
      cells in the in vitro model, and to correlate these data with the clinical
      evidence of our patients. METHODS: We used a sandwich ELISA to quantitate IL-6
      and TGF-beta 1 levels in sera, plasma, and supernatants, and an imunofluorescence
      technique to evaluate IL-6 producing cells in our patients. RESULTS: IL-6 was
      detected in sera from 8 of 20 patients and no controls (p < 0.05). A significant
      increase of IL-6 production was observed in both spontaneous and
      phytohemagglutinin (PHA) induced cultures of PBMC from patients with SSc vs
      controls. No differences in TGF-beta 1 production were observed, either in sera
      or supernatants, between patients and controls. A significant increase of IL-6
      synthesizing cells was observed after 3 h of PHA stimulation in patients vs
      controls (p < 0.05). CONCLUSION: Spontaneous IL-6 production and the higher
      number of IL-6 producing cells in patients with SSc suggest that these cells have
      been already primed in vivo. The absence of PBMC primed for TGF-beta 1 production
      supports the hypothesis that cells other than lymphocytes produce and secrete
      this cytokine in the skin of patients. Higher serum levels of IL-6 observed in a
      subset of patients did not correlate with either severity or duration of disease.

PMID- 8882035
TI  - Detection of early asymptomatic esophageal dysfunction in systemic sclerosis
      using a new scintigraphic grading method.
AB  - OBJECTIVE: To screen patients with systemic sclerosis (SSc) for esophageal
      disease and to demonstrate a new system of grading dysmotility; to determine the
      relationship between the symptom of dysphagia and the degree of hypomotility
      shown by scintigraphy. METHODS: 301 patients with SSc were studied by esophageal
      scintigraphy using a semisolid orally ingested bolus to detect esophageal
      dysfunction and gastroesophageal reflux. A new system of grading was used to
      quantitate the degree of dysfunction, ranging from grade 0 (normal) to grade 4
      (severe abnormality). RESULTS: 246 (82%) patients in the study population had
      evidence of esophageal hypomotility. Gastroesophageal reflux was noted in 83
      (28%) patient. The largest number of patients (33%) were found to have grade 2
      abnormalities. The number of patients with reflux decreased with increasing
      severity of grade, from grade 2 to grade 4 (35 to 13%). A retrospective study of
      the symptoms of 50 of the total study population showed that increasing severity
      of grade correlated with increasing mean duration of SSc. There was no
      significant relationship between disease subset and the presence or severity of
      esophageal hypomotility. 60% of patients in grades 1 and 2 (i.e. with observed
      dysmotility shown on scintigraphy) had no symptoms of dysphagia. In the more
      severe grades (scan grades 3 and 4), symptoms of dysphagia correlated with
      increase in grade. CONCLUSION: Symptoms may be unreliable in judging the presence
      of extent of esophageal disease in SSc. Esophageal scintigraphy is a useful
      noninvasive screening test for the detection of asymptomatic disease. The new
      grading system provides information that rapidly identifies the stage of
      esophageal disease and gives comparative data for followup and interventional
      studies.

PMID- 8882036
TI  - Initial prevalence and incidence of secondary Raynaud's phenomenon in patients
      with Raynaud's symptomatology.
AB  - OBJECTIVE: To establish the initial prevalence and incidence of secondary
      Raynaud's phenomenon (RP) in an outpatient population presenting with RP and
      assessment of the discriminating and predictive value of the variables of a
      diagnostic program. METHODS: 112 patients (average followup time 46 mo) were
      investigated prospectively. A screening program including anamnestic data,
      clinical examinations, noninvasive angiologic measurements, radiographic
      examinations, and laboratory chemistry was applied initially and repeated every 6
      months. Patients with suspected secondary RP according to the screening underwent
      an extended diagnostic program. RESULTS: Based on the initial screening, 73
      patients were classified as primary RP and 39 patients as suspected secondary RP.
      After examinations of the extended diagnostic program, 16 patients were diagnosed
      as secondary RP (initial prevalence 14.3%). During followup another 5 patients
      were diagnosed as secondary RP (annual incidence 1.4%). Using stepwise logistic
      regression, 7 screening variables were included in a model, leading to 96%
      correct classifications (sensitivity 86%, specificity 100%). Most of these
      variables were also suitable to predict the transition to secondary RP. An
      alternative classification based on a total symptoms score led to 94% correct
      classifications (sensitivity 86%, specificity 96%). CONCLUSION: The diagnostic
      program proved adequate and effective. Patients with RP and related arterial
      circulatory disorder showed a different clinical course than patients with an
      immunopathogenesis. A combination of several variables seems to be superior, with
      respect to the prediction and differentiation of secondary RP, to an approach
      based on single variables.

PMID- 8882037
TI  - Reduced serum creatine kinase activity in inflammatory rheumatic diseases.
AB  - OBJECTIVE: To determine if serum CK activity is reduced in inflammatory rheumatic
      diseases and to evaluate whether this phenomenon is linked to disease activity or
      steroid therapy. METHODS: Serum CK activity was measured in patients with
      systemic lupus erythematosus (SLE, n = 52), rheumatoid arthritis (RA, n = 80),
      ankylosing spondylitis (AS, n = 82), spondyloarthropathies other than AS (SpA, n
      = 22), and a miscellaneous group (MI, n = 27), and in 103 control patients with
      noninflammatory arthropathies (NIA). Laboratory variables of inflammatory
      activity such as ESR, CRP, platelet count, and hemoglobin (and anti-DNA
      antibodies and complement levels in SLE) were measured at the same time. Daily
      dose of steroids was also evaluated. RESULTS: Serum CK activity was significantly
      reduced in SLE (mean +/- SD: 49 +/- 41 IU/l), RA (68 +/- 41 IU/l), SpA (88 +/- 53
      IU/l), and MI (75 +/- 32 IU/l) compared to controls (111 +/- 38 IU/l) (p = 0.002
      for SpA and p < 0.001 for the other groups). No differences in CK values were
      observed between AS and controls, although AS patients with peripheral arthritis
      had lower serum CK activity than those without (80 +/- 32 vs 121 +/- 62 IU/l,
      respectively, p < 0.05. ESR, CRP, and platelets correlated inversely with CK
      values in RA, AS, and MI. In the SpA group only ESR correlated inversely with CK.
      In SLE, a positive correlation was found between CK values and CH50 and a
      negative one with anti-DNA levels. Patients taking steroids had significantly
      lower CK activity than those without corticotherapy. However, multivariate
      analysis showed that only inflammatory activity and no steroids had an effect in
      reducing CK activity. CONCLUSION: Serum CK activity is significantly reduced in
      several inflammatory rheumatic diseases. Inflammatory activity seems to play the
      major role in this phenomenon.

PMID- 8882038
TI  - Decreased reflex tearing is associated with lymphocytic infiltration in lacrimal
      glands.
AB  - OBJECTIVE: To investigate whether reflex tearing measured by the Schirmer test
      with nasal stimulation is better correlated with lymphocytic infiltration of the
      lacrimal gland and is thus a more appropriate test for Sjogren's syndrome (SS).
      METHODS: 272 patients with dry eye (age 55.5 +/- 13.5 years) with regular
      Schirmer test results < 10 mm were recruited for the study. They were divided
      into 2 groups depending on the results of the Schirmer test with nasal
      stimulation. 24 age and sex matched patients from each group were selected for
      lacrimal gland biopsy and 10 patients for salivary gland biopsy, and the levels
      of systemic autoantibodies and degrees of ocular surface staining and lymphocytic
      infiltration of the lacrimal and salivary glands were compared. RESULTS: Of the
      272 patients, 187 (68.8%) had good reflex tearing (GT) and 85 (31.2%) had poor
      reflex tearing (PT). There were no significant differences in the age or sex of
      the 2 groups. Lymphocytic infiltration of the lacrimal gland was observed in 7 GT
      cases and 22 PT cases out of 24 cases. Lymphocytic infiltration of the salivary
      gland was also higher in the PT (6 of 10) than the GT group (2 of 10).
      CONCLUSION: Evaluation of reflex tearing by the Schirmer test with nasal
      stimulation identifies 2 groups of patients with dry eye. Those with poor reflex
      tearing were more likely to have autoantibodies and lymphocytic infiltration of
      the exocrine glands consistent with SS.

PMID- 8882039
TI  - Cytokines in Behcet's disease.
AB  - OBJECTIVE: Cytokines take place in immunologic and inflammatory reactions. The
      aim of this study was to describe the roles of various cytokines in the
      pathogenesis of Behcet's disease (BD). METHODS: Serum levels of interleukin-1
      beta (IL-1 beta), interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R),
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were studied in
      24 patients with active BD and 15 healthy adults as controls, by ELISA technique.
      Patients were separated into 2 groups according to the number of active organ
      systems (Group I: < 3 vs Group II: > or = 3). RESULTS: sIL-2R and age adjusted
      TNF-alpha levels were higher in patients with BD compared to controls (p = 0.004
      and p = 0.002, respectively). But the median concentrations of Group I and Group
      II were not different. Serum levels of IL-1 beta, IL-2 and IL-6 were similar to
      the control group. CONCLUSION: High serum levels of sIL-2R and TNF-alpha indicate
      activation of the immune system in BD. But this finding may not be useful as a
      marker of disease activity.

PMID- 8882040
TI  - Silent myocardial ischemia in Behcet's disease.
AB  - OBJECTIVE: Behcet's disease (BD) is a multisystemic disorder usually described as
      a triple symptom complex consisting of aphthous stomatitis, genital ulcerations,
      and uveitis. Vasculitis is a key feature of the disease, which may lead to
      functional disturbances in highly vascularized organs. However, cardiac
      involvement is seldom recognized. We investigated the prevalence of silent
      myocardial ischemia (SMI) in BD as the clinical presentation of microvascular
      disease. METHODS: Ambulatory cardiac monitoring (Holter) was used in 36 patients
      with BD to detect silent myocardial ischemia. 201Thallium myocardial perfusion
      scintigraphy and radionuclide ventriculography were also performed. All patients
      fulfilled International Study Group for Behcet's Disease criteria and 11 of them
      had major vascular involvement. The same method was also performed on 38 control
      subjects for comparison of SMI positivity in patients with BD. RESULTS:
      Ambulatory cardiac monitoring was performed for 9.2 +/- 0.9 h, mean heart rate
      was 82 +/- 9 bpm, and no serious rhythm disturbance was recorded. SMI was
      described in 9 of 36 patients (25%) (median age 38 years, range 30-46) as ST
      segment depression of 3.00 +/- 0.42 mm with a duration of 4.01 +/- 0.9 min. One
      SMI positivity only was recorded in the control group in a 52-year-old man with a
      stenotic lesion in the left anterior descending coronary artery (p < 0.001).
      Eight of 9 patients with SMI showed a partially reversible myocardial perfusion
      defect after exertion, and 7 demonstrated some degree of left ventricular wall
      motion abnormality by radionuclide ventriculography. Coronary angiography was
      normal in 7 of 9 patients with SMI. Additionally, 7 of 9 patients with SMI had
      major vascular involvement, while only 4 of 27 without SMI had major vascular
      disease (p = 0.0022). CONCLUSION: SMI incidence is significantly higher in BD
      compared to the control group. Impaired endothelial cell function may be the
      underlying cause in the pathogenesis of BD or of its vascular complications such
      as SMI.

PMID- 8882041
TI  - Isometric strength measurements of knee extensors in women with osteoarthritis of
      the knee.
AB  - OBJECTIVE: To compare torque-angle characteristics of the knee extensors of women
      with and without osteoarthritis (OA) of the knee, and to determine the
      reliability of these measures. METHODS: The isometric torque of the knee
      extensors of both legs was tested on 3 occasions in 17 women with OA of the knee
      and 17 healthy women. Tests were performed on an isokinetic dynamometer at 3 knee
      angles (30 degrees, 60 degrees, 90 degrees). The peak torque values were
      subjected to 4 way analysis of variance (group vs leg vs angle vs time), and
      intraclass correlation coefficients were calculated. RESULTS: The reliability
      coefficients for repeated measures of isometric torque varied from 0.83 to 0.94
      in the OA group and from 0.90 to 0.95 in the comparison group. The ANOVA and post
      hoc analyses revealed that the OA group had significantly (p < 0.05) lower knee
      extensor torque than the comparison group, and that the more symptomatic OA knee
      had lower torque than the contralateral limb. The torque was different across the
      3 angles, but the torque-angle relationship was the same for both groups.
      CONCLUSION: Isometric torque of the knee extensors can be measured reliably in
      women with OA of the knee. The torque is lower in women with OA than in women
      with no knee problems, and the changes are similar across different knee angles.

PMID- 8882042
TI  - Are risk factors for patellofemoral and tibiofemoral knee osteoarthritis
      different?
AB  - OBJECTIVE: To determine whether patellofemoral (PF), tibiofemoral (TF), and
      combined patterns of knee osteoarthritis (OA) differ in their strengths of
      associations with any of the known risk factors for knee OA, and especially to
      evaluate whether body mass index (BMI) correlates with all 3 patterns, or only
      with tibiofemoral disease, as previously suggested. METHODS: We obtained
      anteroposterior and lateral knee radiographs on 608 participants at the 22nd
      biennial examination of the Framingham cohort study (1992-3). The presence or
      absence of OA in the TF and PF compartments of each knee was scored, and subjects
      were classified on the basis of the pattern of compartmental involvement in their
      2 knees. The strength of association of age, sex, BMI, chondrocalcinosis, and
      knee injury was computed for PF, TF, and combined pattern of knee OA using
      multiple logistic regression. RESULTS: The mean age and BMI of the sample were
      80.7 yrs (SD 5.0) and 25.4.kg-2 (SD 3.7), respectively. PF, TF, and combined
      patterns of knee OA were present in 5.3, 23.0 and 19.7%, respectively. Elevated
      BMI was a risk factor for all 3 patterns of disease (adjusted OR for highest vs
      lowest tertile of BMI 3.7, 1.9, and 7.0 for PF, TF, and combined pattern,
      respectively). Risk factor profiles were broadly similar for TF and PF OA, with
      the possible exception of knee injury in men (adjusted OR = 2.0 for PF, 3.7 for
      TF OA). Risk factors were generally more strongly associated with the combined
      pattern of OA. CONCLUSION: Obesity is an important risk factor for PF, TF, and
      combined patterns of knee OA. The relationships of these patterns with the risk
      factors investigated here appear similar and are strongest for the combined
      pattern.

PMID- 8882043
TI  - Arthroscopic anterior cruciate ligament transection induces canine
      osteoarthritis.
AB  - OBJECTIVE: To determine whether arthroscopic anterior cruciate ligament (ACL)
      transection in the canine knee can be an effective alternative method for
      creating canine osteoarthritis (OA). METHODS: Six adult dogs underwent
      arthroscopic examination of the left knee with a 2.7 mm 30 degrees fiberoptic
      arthroscope. The articular surfaces of the femoral condyles, tibial plateaus, and
      patella were examined for evidence of OA. The ACL was directly visualized and
      transected. Care was taken to avoid iatrogenic articular cartilage injury. The
      animals were sacrificed 2 to 6 months after ACL transection. Both the ACL
      transected and ACL intact knees from each animal were assessed for gross
      pathology and histology. RESULTS: The dogs experienced minimal perioperative pain
      and rapidly returned to their preinjury level of activity. Gross and histological
      examination of articular cartilage confirmed this approach induced OA in every
      ACL transected knee. No contralateral ACL intact knee developed degenerative OA
      changes. CONCLUSION: Arthroscopic ACL transection is an effective method for
      creating canine OA. This approach has several methodological advantages relative
      to other techniques.

PMID- 8882044
TI  - Bilateral canine model of osteoarthritis.
AB  - OBJECTIVE: To determine whether bilateral arthroscopic anterior cruciate ligament
      (ACL) transection creates symmetrical osteoarthritis (OA) in canine knees.
      METHODS: Six dogs underwent bilateral arthroscopic ACL transections. The animals
      were sacrificed at intervals ranging from 2 to 12 months post ACL transection.
      Both knees in each animal were assessed for gross pathology, histology, and
      biochemistry. RESULTS: The limited invasiveness of arthroscopic ACL transection
      allowed bilateral ACL transections to be performed with minimal animal morbidity.
      Gross pathological, histological, and biochemical assessments of bilaterally ACL
      transected canine knees consistently confirmed the induction of OA changes in
      both knees. Of note, there was no significant difference in the degree of
      articular cartilage degeneration created in each pair of knees. CONCLUSION:
      Bilateral ACL transection induces symmetrical canine knee OA. This approach
      provides a potent model for investigating fundamental OA mechanisms and
      therapeutic approaches, since one knee can be experimentally manipulated while
      the other knee is used as a control. This allows each animal to be its own
      internal control, avoiding the interanimal variability associated with the
      unilateral canine OA model.

PMID- 8882045
TI  - Determinants of physician confidence in the primary care management of
      musculoskeletal disorders.
AB  - OBJECTIVE: To examine the determinants of confidence in managing musculoskeletal
      (MSK) disorders among primary care physicians. METHOD: A self-administered
      questionnaire was mailed to a stratified (by urban/rural location) random sample
      of 798 Ontario primary care physicians who were members of the College of Family
      Physicians of Canada. Two mailings and a reminder postcard were used to increase
      response. As the main outcome measure, confidence was measured on a 10 point
      Likert-type scale. RESULTS: The overall response rate was 68.3%. Most respondents
      were practising in a full time group setting; their average age was 40.3 years.
      Respondents were significantly more confident in performing a comprehensive
      cardiovascular examination than a MSK examination. Highest levels of confidence
      were observed for using nonsteroidal antiinflammatory drugs and managing common
      MSK disorders. Lower scores were reported for doing a joint injection/aspiration.
      Rural physicians were more confident than urban physicians in doing a joint
      injection/aspiration and monitoring patients who were taking disease modifying
      agents. Previous continuing medical education (CME) was significantly (p < 0.01)
      related to all confidence outcomes using multiple regression analysis. For many
      outcomes, men reported higher confidence scores than women after adjustment for
      various demographic characteristics. CONCLUSION: CME may be the most important
      and modifiable variable to improve physician management of MSK disorders.

PMID- 8882046
TI  - The articular prognosis of pauciarticular onset juvenile arthritis is not
      influenced by the presence of uveitis.
AB  - OBJECTIVE: The purpose of our retrospective study was to determine the longterm
      articular prognosis in patients with pauciarticular onset juvenile arthritis (JA)
      with and without uveitis. METHODS: Twenty-nine patients with pauciarticular onset
      JA with uveitis were compared to 86 without uveitis, matched for sex, age at
      disease onset, and duration of followup. All patients had a minimum followup of 6
      years from disease onset. The outcome of arthritis was evaluated by: (1)
      progression to polyarticular disease; (2) hip involvement; (3) radiographic
      evidence of articular erosions; (4) significant functional disability at the last
      visit. RESULTS: There was no statistically significant difference between the 2
      groups in the severity variables considered, single or combined. CONCLUSION: Our
      data suggest that the presence of uveitis does not influence the longterm
      articular prognosis in pauciarticular onset JA.

PMID- 8882047
TI  - Sulfasalazine therapy for juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To determine the safety and therapeutic potential of sulfasalazine
      (SSZ) in the treatment of a large cohort of patients with juvenile rheumatoid
      arthritis (JRA). METHODS: All patients who required the addition of a second line
      agent were offered SSZ and assessed at regular intervals. Thirty patients took
      SSZ as their sole drug therapy. One hundred thirty-nine patients with an average
      age of 11.5 yrs (range 1.5-21.8 yrs) took the medication. The duration of
      symptoms at the start of treatment was 30 mo (1-130 mo). All subtypes of JRA were
      included in the study group. Patients were treated for a mean of 13 mo (1-42 mo)
      with 31 mg/kg/day of SSZ. Significant improvement was defined as 50% decrease in
      the number of joints with active arthritis; or 50% decrease in the number of
      joints with effusion; or 50% decrease in total degrees of joint contractures; or
      normalization of an elevated erythrocyte sedimentation rate within 12 months of
      starting treatment. Data on adverse reactions, remissions, and treatment failure
      were also collected. RESULTS: One hundred two patients (73%) had significant
      improvement after starting SSZ. Fifty-six patients (40%) were able to stop all
      other medication at an average of 9.5 mo. Thirty-nine patients (28%) remitted and
      discontinued all medication. Twenty-three patients (17%) discontinued the drug
      for adverse reactions. All reactions resolved completely when the drug was
      discontinued. CONCLUSION: SSZ is safe and appears to be an effective primary or
      second line therapy for JRA, and should be studied further in a multi
      institutional, placebo controlled study.

PMID- 8882048
TI  - Residual serologic reactivity in children with resolved Lyme arthritis.
AB  - OBJECTIVE: To define the pattern of persistent antibody response in children with
      resolved Lyme arthritis. METHODS: From a cohort of 67 children with Lyme
      arthritis followed in our department since 1989, 19 were selected using these
      criteria: All patients (1) were asymptomatic; (2) had an ELISA titer < or =
      1:160; (3) had been in treatment a minimum of 6 months. Their initial and late
      samples were assessed by Western blot and the pattern of reactivity was analyzed.
      RESULTS: The mean interval between treatment and last sample was 9.6 months (6
      23). Analysis of the last sample showed that only 5/19 were negative by ELISA and
      4/19 were at the cutoff limit (1:80). Only 6 patients had fewer than 4 reactive
      bands, 4 had 4 bands, and 9 had 5-11 bands on Western blot. The 41, 39, and 60
      kDa were the most commonly observed reactive bands at last evaluation. 31 and 34
      kDa bands, while relatively common in initial samples (36%), became uncommon (5%)
      on late samples. A significant finding was the absence of IgM reactivity in
      18/19: 1/19 had 41 kDa reactivity. Only 4 patients had both ELISA (< 1:80) and
      Western blot tests negative (< 5 reactive bands). CONCLUSION: All patients with
      resolved Lyme arthritis continue to show serologic reactivity beyond 6 months of
      therapy. 68% of the patients satisfy Western blot criteria for positivity in our
      laboratory. IgM reactivity to any antigen was minimal and IgG reactivity against
      the 41 kDa antigen, considered diagnostic of infection in initial samples by some
      laboratories, is very common (16/19).

PMID- 8882049
TI  - Studies on associations of antinuclear antibodies with antibodies to an
      uveitogenic peptide of retinal S antigen in children with uveitis.
AB  - OBJECTIVE: To determine if, in children with uveitis, antinuclear antibodies
      (ANA) are associated with antibodies to an uveitogenic peptide of a soluble
      retinal antigen and to the homologous nuclear antigen, histone 3 (H3). ANA occur
      in most children with juvenile rheumatoid arthritis (JRA) and associated uveitis.
      An uveitogenic segment of retinal soluble antigen (S antigen peptide) is
      homologous with a similarly uveitogenic peptide of H3. We investigated a possible
      association between ANA positivity, antibodies to H3, and antibodies to the
      uveitogenic S antigen peptide. METHODS: The sera of 31 children with uveitis (20
      of whom had associated JRA) were tested for the presence of ANA by indirect
      immunofluorescence. Antibodies to H3 and to an uveitogenic peptide of S antigen
      (an 18 mer segment having the amino acid sequence DTNLASSTIIKEGIDKTV) were
      measured by enzyme immunoassay. RESULTS: 19 of 20 children (95%) with JRA and
      associated uveitis and none of 11 with uveitis not associated with JRA had
      positive tests for ANA (X2 = 14.97; p < 0.00001). 16 of 19 ANA positive sera from
      subjects with JRA (84%) displayed reactivity with the chromosomal regions of
      metaphase cells. 9 of 20 patients with JRA with uveitis (45%) and 2 of 11
      patients (18%) with uveitis not associated with JRA had antibodies to H3. Two
      uveitic patients with JRA (10%) and 2 non-JRA patients with uveitis (18%) reacted
      with S antigen peptide. Antibodies to H3 occurred significantly more frequently
      in children with uveitis than in all adult control subjects (X2 = 12.98; p =
      0.003) and in adults with uveitis (X2 = 5.62; p = 0.022). CONCLUSION: Humoral
      immune responses to the uveitogenic peptide of S antigen and the homologous H3
      antigen appear not to be uniquely important in the immunopathology of uveitis
      associated with JRA. Antibodies to isolated H3 do not exclusively account for ANA
      positivity in the uveitic patient with JRA. A unique immunopathogenic mechanism
      for the development of uveitis associated with JRA is suggested by the
      observations that (1) children with uveitis associated with JRA are more likely
      to be ANA positive than children with uveitis not associated with JRA, and (2)
      children with uveitis associated with JRA are significantly more likely to be ANA
      positive and to have antibodies to H3 than adults with uveitis.

PMID- 8882050
TI  - Prolactin hormone in juvenile systemic lupus erythematosus: a possible
      relationship to disease activity and CNS manifestations.
AB  - OBJECTIVE: In this prospective study we aimed to determine serum prolactin (PRL)
      concentrations among patients with prepubertal juvenile systemic lupus
      erythematosus (SLE) and their possible relationship to disease activity and/or
      manifestations. METHODS: Serum PRL was estimated by immunoradiometric assay in 33
      prepubertal children with SLE and 20 healthy controls. Patients had complete
      clinical and laboratory investigations. Disease activity was evaluated using the
      Systemic Lupus Activity Measurement Index (SLAM). RESULTS: The mean serum PRL
      level was higher in juvenile SLE than healthy controls; however, the difference
      was not statistically significant. There was no significant correlation between
      the serum PRL levels and total SLAM score among our patients. Serum PRL levels
      were significantly correlated with erythrocyte sedimentation rate (r = +0.352, p
      < 0.05) and inversely with each of total leukocyte count (r = -0.504, p < 0.01)
      and lymphocyte count (r = -0.408, p < 0.05). Hyperprolactinemia was found in 3
      (9%) of the children with SLE but not in controls. All 3 patients with
      hyperprolactinemia (100%) had central nervous system (CNS) manifestations
      compared to only 3 (10%) patients (p < 0.003) with normal PRL level. CONCLUSION:
      Our results suggest a subset of juvenile SLE characterized by hyperprolactinemia
      and increased prevalence of CNS manifestations. A possible relationship between
      serum PRL concentrations and disease activity in juvenile SLE was found. Our data
      point to the importance of further studies of the role of PRL in immunomodulation
      of pediatric rheumatic diseases.

PMID- 8882051
TI  - C1 inhibitor deficiency in a patient with rheumatoid arthritis--increased risk of
      adverse effects of penicillamine?
AB  - We report the coincidence of hereditary angioedema and rheumatoid arthritis in a
      male patient and in his father. During treatment with D-penicillamine the patient
      developed a transient lupus-like disorder with glomerulonephritis that resolved
      when D-penicillamine was discontinued. He later was diagnosed with malignant
      lymphoma. Impaired classical complement pathway function could have contributed
      to development of the drug reaction.

PMID- 8882052
TI  - Interferon alpha 2a therapy for urticarial vasculitis with angioedema apparently
      following hepatitis A infection.
AB  - A 68-year-old woman with a 5 yr history of chronic recurrent urticarial
      vasculitis with angioedema, refractory to conventional treatment including
      glucocorticosteroids, H1 and H2 blockers, nonsteroidal antiinflammatory agents,
      methotrexate, hydroxychloroquine, dapsone, azathioprine, intravenous gamma
      globulin, and plasma exchange, was successfully treated with interferon alpha 2a.
      The cause of the urticarial vasculitis remains unknown, although its onset
      followed a hepatitis A infection. This is the first report of the successful use
      of interferon alpha for chronic urticarial vasculitis/angioedema.

PMID- 8882053
TI  - Thrombotic thrombocytopenic purpura in adult Still's disease.
AB  - We describe 2 patients with adult Still's disease who developed thrombotic
      thrombocytopenic purpura (TTP) and were successfully treated. Although TTP has
      been associated with autoimmune diseases, usually with systemic lupus
      erythematosus or various forms of vasculitis, it has rarely been observed in
      patients with adult Still's disease. This uncommon coexistence of 2 clinical
      entities may indicate similar pathogenetic mechanisms.

PMID- 8882054
TI  - Accelerated progressive systemic sclerosis in a patient with hypothenar hammer
      syndrome.
AB  - We describe the first case of hypothenar hammer syndrome followed by accelerated
      systemic sclerosis (SSc). A sawmill worker with repeated wrist trauma presented
      with bilateral digital ischemia and fingertip ulcerations. Hypothenar hammer
      syndrome involving both hands was diagnosed based on classic angiographic studies
      showing occlusion of the ulnar arteries at the level of the hamate and occlusions
      of multiple digital arteries. He also had minimal digital swelling,
      telangiectatic lesions on the fingers, and a positive FANA test. Resected ulnar
      arteries showed clearcut changes compatible with both microtrauma and SSc. After
      surgical repair of both ulnar arteries, he rapidly developed severe SSc with
      significant cardiopulmonary involvement.

PMID- 8882055
TI  - Female genital tract giant cell arteritis associated with occult temporal
      arteritis.
AB  - Giant cell arteritis (GCA) of the female genital tract has been described as an
      incidental finding, but associated temporal arteritis (TA) has been rarely
      reported. We describe a case of female genital tract GCA associated with occult
      giant cell TA, which in the absence of cranial symptoms was confirmed by a random
      temporal artery biopsy. The patient remains asymptomatic at 12 month followup
      after treatment with prednisolone and azathioprine.

PMID- 8882056
TI  - Liver involvement in familial granulomatous arthritis (Blau syndrome).
AB  - We describe hepatic granulomata in a patient with familial granulomatous
      synovitis (Blau syndrome). While visceral involvement is a previously
      unrecognized manifestation of Blau syndrome, its occurrence has been well
      documented in a similar disease, childhood sarcoidosis. Our findings suggest that
      the 2 conditions (Blau syndrome and childhood sarcoidosis) are more closely
      related than thought.

PMID- 8882057
TI  - SAPHO syndrome and pyoderma gangrenosum: is it fortuitous?
AB  - Pyoderma gangrenosum is well known as an associated feature of inflammatory bowel
      disease (IBD). Recently, higher than normal prevalence of IBD in patients with
      the SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome has been
      reported. However, the association of pyoderma gangrenosum with SAPHO syndrome
      without definitely excluded IBD has not been reported. We describe a case that
      suggests a possible connection between these 2 entities.

PMID- 8882058
TI  - Folinic acid supplementation in patients with juvenile rheumatoid arthritis
      treated with methotrexate.

PMID- 8882059
TI  - The benefit/risk ratio of low dose cyclosporin A in rheumatoid arthritis.

PMID- 8882060
TI  - Evaluation of disease activity in rheumatoid arthritis and other arthritides
      using 99mTechnetium labeled nonspecific human immunoglobulin.

PMID- 8882061
TI  - Pancytopenia related eosinophilia in rheumatoid arthritis.

PMID- 8882062
TI  - Photochemotherapy for refractory rheumatoid arthritis.

PMID- 8882063
TI  - An update on the Bath Ankylosing Spondylitis Disease Activity and Functional
      Indices (BASDAI, BASFI): excellent Cronbach's alpha scores.

PMID- 8882064
TI  - An update on the Bath Ankylosing Spondylitis Disease Activity and Functional
      Indices (BASDAI, BASFI): excellent Cronbach's alpha scores.

PMID- 8882065
TI  - Serum cytokine and cytokine receptor levels in patients with giant cell arteritis
      during corticotherapy.

PMID- 8882066
TI  - Benign hypergammaglobulinemic purpura and anti-Ro(SSA) antibodies in
      undifferentiated connective tissue disease.

PMID- 8882067
TI  - Antineutrophil cytoplasmic antibodies in leptospirosis.

PMID- 8882068
TI  - Cyclophosphamide treatment of paraquat poisoning.

PMID- 8882069
TI  - Pulse therapy with cyclophosphamide and methylprednisolone in patients with
      moderate to severe paraquat poisoning: a preliminary report.
AB  - BACKGROUND: Severe paraquat poisoning causes considerable morbidity and
      mortality. High doses of cyclophosphamide and dexamethasone have been used to
      treat patients with paraquat poisoning, but with mixed results. The use of pulse
      methylprednisolone and cyclophosphamide was investigated in the treatment of
      moderately severe paraquat poisoning. METHODS: During a six-year period 87
      patients with paraquat poisoning were admitted to hospital, of whom 33 had
      moderate to severe intoxication. Seventeen patients received conventional
      treatment and served as historical controls, and 16 received intravenous
      infusions of cyclophosphamide 1 g daily for two days and methylprednisolone 1 g
      daily for three days. RESULTS: There were no differences between the groups in
      age, sex, severity of paraquat poisoning (as assessed by urine dithionite tests),
      or in the time elapsed from ingestion to presentation at hospital or to the
      beginning of haemoperfusion. No differences were seen in biochemical measurements
      on the third day after paraquat poisoning. The mortality in the pulse therapy
      group was lower than that in the control group (4/16 (25%) versus 12/17 (70.6%),
      p = 0.01). All fatalities were from progressive respiratory failure. CONCLUSIONS:
      Pulse therapy with cyclophosphamide and methylprednisolone may be effective in
      preventing respiratory failure and reducing mortality in patients with moderate
      to severe paraquat poisoning. Further controlled studies are needed to confirm
      this and to establish the mechanisms.

PMID- 8882070
TI  - Safety of fibreoptic bronchoscopy in asthmatic and control subjects and effect on
      asthma control over two weeks.
AB  - BACKGROUND: Concerns remain about the safety of bronchoscopy in asthma and there
      are few data on the effect of this procedure on asthma control in the days or
      weeks following bronchoscopy. METHODS: In an initial study of bronchoalveolar
      lavage and bronchial biopsies in asthmatic and control subjects, data on peak
      expiratory flow rates (PEFR) collected prospectively before and after the
      procedure were available from 21 of the 29 asthmatic subjects studied. These
      showed a median 23% fall in PEFR from baseline after bronchoscopy (range 3-58%).
      To determine whether this fall in PEFR following bronchoscopy reflected
      bronchospasm or the effect of sedation, PEFR and spirometric tests were performed
      during the two hours following bronchoscopy in a further study of 15 symptomatic
      asthmatic subjects and 20 non-asthmatic controls. To examine the effect on asthma
      control, asthmatic patients recorded PEFR, symptom scores, and medication use for
      two weeks before and after bronchoscopy. RESULTS: After bronchoscopy with
      bronchial biopsies there was no difference between the median maximal fall in
      either PEFR or arterial oxygen saturation between the 15 asthmatic patients
      (10.4% and 4%, respectively) and 20 controls (12% and 3%). Moreover, there were
      no significant changes in PEFR, symptom score, or medication use by the asthmatic
      subjects in the two weeks after bronchoscopy when compared with the two weeks
      before bronchoscopy. CONCLUSIONS: Fibreoptic bronchoscopy is well tolerated in
      asthmatic subjects. Falls in PEFR in both asthmatic and non-asthmatic subjects
      after bronchial biopsy may reflect the effects of sedation rather than
      bronchospasm. Additional bronchoalveolar lavage may cause bronchoconstriction.
      Careful monitoring is therefore essential. Peak flow monitoring up to two weeks
      after bronchoscopy with bronchial biopsy revealed no delayed effects on asthma
      control.

PMID- 8882071
TI  - Study of the aetiology of wheezing illness at age 16 in two national British
      birth cohorts.
AB  - BACKGROUND: Data from two national British birth cohorts were used to measure the
      increase in prevalence of wheezing illness at age 16 between 1974 and 1986, and
      to investigate the role of several potential risk factors in the increase.
      METHODS: The occurrence of self-reported asthma or wheezy bronchitis within the
      past year, and the frequency of attacks of wheezing illness at age 16, were
      compared in 11,262 and 9266 children born in one week of 1958 and 1970,
      respectively. The effects of several putative risk factors for asthma--including
      birth weight, maternal age, birth order, breast feeding, maternal smoking in
      pregnancy, child's personal smoking, and father's social class--on the change in
      occurrence of wheezing illness at age 16 were assessed by multiple logistic
      regression. RESULTS: The annual period prevalence of asthma or wheezy bronchitis
      at age 16 increased from 3.8% in 1974 to 6.5% in 1986 (prevalence ratio (PR) =
      1.71, 95% CI 1.52 to 1.93). The proportion of children experiencing attacks more
      than once a week increased from 0.2% to 0.7% (PR = 3.77, 95% CI 2.28 to 6.23).
      The prevalence of self-reported eczema and hayfever within the past year doubled
      between 1974 and 1986, suggesting that the increase in asthma was part of a
      general increase in the prevalence of atopic disease. However, in the complete
      dataset, after adjustment for the effects of the risk factors studied, the
      prevalence odds ratio for asthma or wheezy bronchitis in 1986 compared with 1974
      was virtually unchanged from the unadjusted value at 1.77 (95% CI 1.46 to 2.15).
      CONCLUSION: The prevalence of wheezing illness in British teenagers increased by
      approximately 70% between 1974 and 1986. This increase appears to have occurred
      in the context of a general increase in atopic disease and was largely
      unexplained by changes in the distribution of maternal age, birth order, birth
      weight, infant feeding, maternal smoking, active smoking by the child, or
      father's social class.

PMID- 8882073
TI  - Effects of cessation of terbutaline treatment on airway obstruction and
      responsiveness in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Cessation of regular therapy with inhaled beta 2 agonists in patients
      with asthma may lead to a temporary deterioration of lung function and airway
      responsiveness. Few such studies have been reported in patients with chronic
      obstructive pulmonary disease (COPD), so an investigation was carried out to
      determine whether rebound airway responsiveness and rebound bronchoconstriction
      also occurs in COPD and if there is any relationship with the dose of beta 2
      agonist being used. METHODS: Lung function (forced expiratory volume in one
      second (FEV1) and peak expiratory flow (PEF)), airway responsiveness (PC20
      methacholine (PC20)) and symptoms were assessed in a double blind, placebo
      controlled crossover study during and after cessation of two weeks regular
      treatment with placebo, and low dose (250 micrograms) and high dose (1000
      micrograms) inhaled terbutaline via a dry powder inhaler (Turbohaler) all given
      three times a day. Sixteen non-allergic patients with COPD of mean (SD) age 58.7
      (6.5) years, FEV1 57.1 (12.8)% of predicted, and reversibility on 1000 micrograms
      terbutaline of 4.5 (3.5)% predicted were studied. PC20 and FEV1 were measured 10,
      14, 34 and 82 hours after the last inhalation of terbutaline or placebo.
      Measurements performed at 10, 14, and 34 hours were expressed relative to 82 hour
      values in each period, transformed into an area under the curve (AUC) value and
      analysed by ANOVA. RESULTS: Mean morning and evening PEF increased during
      terbutaline treatment. PC20 and FEV1 did not change after cessation of
      terbutaline treatment. CONCLUSIONS: Cessation of regular treatment with both low
      and high dose inhaled terbutaline does not result in a rebound
      bronchoconstriction and rebound airway responsiveness in patients with COPD.

PMID- 8882072
TI  - Breathing pattern and carbon dioxide retention in severe chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: The factors leading to chronic hypercapnia and rapid shallow
      breathing in patients with severe chronic obstructive pulmonary disease (COPD)
      are not completely understood. In this study the interrelations between chronic
      carbon dioxide retention, breathing pattern, dyspnoea, and the pressure required
      for breathing relative to inspiratory muscle strength in stable COPD patients
      with severe airflow obstruction were studied. METHODS: Thirty patients with COPD
      in a clinically stable condition with forced expiratory volume in one second
      (FEV1) of < 1 litre were studied. In each patient the following parameters were
      assessed: (1) dyspnoea scale rating, (2) inspiratory muscle strength by measuring
      minimal pleural pressure (PPLmin), and (3) tidal volume (VT), flow, pleural
      pressure swing (PPLsw), total lung resistance (RL), dynamic lung elastance
      (ELdyn), and positive end expiratory alveolar pressure (PEEPi) during resting
      breathing. RESULTS: Arterial carbon dioxide tension (PaCO2) related directly to
      RL/PPLmin, and ELdyn/PPLmin, and inversely to VT and PPLmin. There was no
      relationship between PaCO2 and functional residual capacity (FRC), total lung
      capacity (TLC), or minute ventilation. PEEPi was similar in eucapnic and
      hypercapnic patients. Expressing PaCO2 as a combined function of VT and PPLmin
      (stepwise multiple regression analysis) explained 71% of the variance in PaCO2.
      Tidal volume was directly related to inspiratory time (TI), and TI was inversely
      related to the pressure required for breathing relative to inspiratory muscle
      strength (PPLsw, %PPLmin). There was an association between the severity of
      dyspnoea and both the increase in PPLsw (%PPLmin) and the shortening in TI.
      CONCLUSIONS: The results indicate that, in stable patients with COPD with severe
      airflow obstruction, hypercapnia is associated with shallow breathing and
      inspiratory muscle weakness, and rapid and shallow breathing appears to be linked
      to both a marked increase in the pressure required for breathing relative to
      inspiratory muscle strength and to the severity of the breathlessness.

PMID- 8882074
TI  - Effects of regular salmeterol on lung function and exercise capacity in patients
      with chronic obstructive airways disease.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of single and
      chronic dosing with salmeterol on exercise capacity and lung function in patients
      with chronic obstructive pulmonary disease. METHODS: Twenty nine patients of mean
      (SE) age 64 (1.5) years, forced expiratory volume in one second (FEV1) 42(3)% of
      predicted, and 5-15% reversibility to salbutamol 200 micrograms were randomised
      to receive four weeks treatment with salmeterol 50 micrograms twice daily or
      placebo in a double blind crossover fashion with a one week washout period in
      between. Measurements of spirometric parameters, static lung volumes, and
      exercise capacity were made one and six hours after a single dose, and six hours
      after the final dose of salmeterol or placebo. RESULTS: Salmeterol produced a
      small increase in FEV1 at one and six hours after a single dose, and this was
      maintained after chronic dosing (mean difference and 95% CI versus placebo):
      single dosing at one hour 0.07 (95% CI 0.02 to 0.11) 1, single dosing at six
      hours 0.16 (95% CI 0.09 to 0.22) 1, chronic dosing at six hours 0.11 (95% CI 0.03
      to 0.19) 1. The increase in forced vital capacity (FVC) was greater with
      salmeterol than with placebo six hours after single but not chronic dosing:
      single dosing at six hours 0.17 (95% CI 0.04 to 0.29) 1, chronic dosing at six
      hours 0.02 (95% CI -0.18 to 0.22) 1. Slow vital capacity was increased after
      treatment with salmeterol compared with placebo one and six hours after single
      but not after chronic dosing. There were no significant differences in static
      lung volumes or exercise capacity after single or chronic dosing with salmeterol
      compared with placebo. Patients reported a significantly lower Borg score for
      perceived exertion following the six minute walk after chronic treatment with
      salmeterol compared with placebo. CONCLUSIONS: Salmeterol produced a small
      improvement in spirometric values compared with placebo consistent with the
      degree of reversibility originally shown by the subjects to salbutamol 200
      micrograms. This was not associated with improvements in static lung volumes or
      exercise capacity, but there was some symptomatic benefit in that patients were
      able to walk the same distance in six minutes with less perceived exertion.

PMID- 8882075
TI  - Evaluation of nocturnal bronchoconstriction by all night tracheal sound
      monitoring.
AB  - BACKGROUND: A study was undertaken to evaluate the reliability of a digital
      tracheal sound analyser (ELENS-DSA) in predicting nocturnal changes in airways
      resistance in asthmatic patients. This device allows continuous measurement of
      the proportion of the time occupied by wheezing (Wh%). METHODS: Nocturnal
      polygraphic studies with simultaneous continuous monitoring of tracheal sounds
      and airways resistance were performed in seven patients with nocturnal asthma. In
      order to evaluate the possible bias in wheezing estimation, each tracheal sound
      recording was passed through the automatic analyser and simultaneously monitored
      with earphones by an experienced observer. RESULTS: The device detected audible
      wheezing with an optimal sensitivity and specificity of 70%. Snoring was a minor
      cause of the relatively poor characteristics of the system. A close correlation
      (p < 0.001) between Wh% and airways resistance was observed only in those
      patients with the highest increase in resistance; when the results of all the
      subjects were pooled the correlation observed was poor. The predictive value of
      Wh% in detecting changes in airways resistance during 10 minute intervals was
      lower than 70%. The positive and negative predictive values of Wh% were raised to
      79% and 83%, respectively, for 30 minute intervals. CONCLUSIONS: The ELENS-DSA
      system is a relatively crude means of detecting wheezing and assessing
      bronchoconstriction quantitatively. However, it is able to detect accurately
      nocturnal bronchoconstriction for 30 minute intervals. This finding, along with
      the fact that the monitoring is non-invasive, suggests that it may be a promising
      tool, especially for patients during sleep.

PMID- 8882076
TI  - Longitudinal effects of change in body mass on measurements of ventilatory
      capacity.
AB  - BACKGROUND: In several longitudinal studies changes in body mass and in forced
      expiratory volume in one second (FEV1) have been found to be negatively
      correlated. This paper tests the hypothesis that failure to allow for the
      association can lead to error in the interpretation of longitudinal measurements
      of ventilatory capacity. METHODS: Male shipyard workers (n = 1005) were assessed
      on two occasions with an average interval between measurements of 6.9 years. A
      respiratory symptoms questionnaire, detailed anthropometric measurements, and
      dynamic spirometric tests were undertaken. Multiple regression analysis was used
      to identify variables which contributed to the changes in lung function. RESULTS:
      After allowing for age and growth in stature, a change in body mass of 1 kg was,
      on average, associated with a mean (SE) converse change in FEV1 of 17.6 (2.0) ml,
      and in forced vital capacity (FVC) of 21.1 (2.5) ml. Neglect of changes in body
      mass (which in this context reflected changes in body fat) led to underestimation
      of the longitudinal decline in FEV1 with age and failure to detect significant
      improvements in FEV1, both in smokers following discontinuation of smoking and in
      shipyard welders and caulker/burners as a consequence of leaving their
      employment. The estimated peak ages and associated peak levels of the indices
      were found to differ, depending on whether or not they were expressed at constant
      body mass. CONCLUSIONS: Neglect of changes in body mass can lead to erroneous
      conclusions being drawn from longitudinal measurements of FEV1.

PMID- 8882077
TI  - Effects of lung volume and fatigue on evoked diaphragmatic phonomyogram in normal
      subjects.
AB  - BACKGROUND: A diaphragmatic phonomyogram (PMG) evoked by maximal phrenic nerve
      stimulation at end expiratory lung volume (FRC) has been previously described as
      a good index of changes in diaphragmatic contractility with fatigue. A study was
      undertaken to assess whether this conclusion could be extended to different lung
      volumes. METHODS: Diaphragmatic compound motor action potentials (CMAPs) were
      recorded on each side of the chest by the means of surface electrodes placed over
      the eight intercostal spaces in five healthy subjects. Diaphragmatic PMGs from
      both sides were recorded with condenser microphones fixed to the skin close to
      the CMAP recording electrodes. Oesophageal and gastric balloon tipped catheters
      were employed to measure transdiaphragmatic pressure twitches (TwPDI) which
      served as the standard measure of changes in diaphragmatic contractility. PMG and
      TwPDI responses were compared at different lung volumes over inspiratory capacity
      both before and after fatiguing inspiratory resistive loading. RESULTS: No
      consistent relationship was found in different subjects or on different days in
      the same subject between PMG and lung volume or between PMG and TwPDI. However,
      the PMG:CMAP ratio from both sides at any given lung volume decreased after
      fatigue in roughly the same proportion as the TwPDI. CONCLUSIONS: These results
      show that, although PMG can detect changes in diaphragmatic contractility caused
      by fatigue in normal subjects, lung volume changes need to be controlled and each
      subject should serve as his or her own control.

PMID- 8882078
TI  - Mortality rates from cryptogenic fibrosing alveolitis in seven countries.
AB  - BACKGROUND: Registered mortality from cryptogenic fibrosing alveolitis (CFA) in
      England and Wales has increased substantially since the specific International
      Classification of Diseases code for CFA was introduced in 1979. However, since a
      significant proportion of deaths from CFA are misclassified as post inflammatory
      fibrosis (PIF), it is possible that the observed rise in CFA mortality is due to
      diagnostic transfer from this code. To investigate this, and to assess mortality
      trends in other countries, annual CFA and PIF mortality data from England and
      Wales, USA, Australia, Scotland, Canada, New Zealand, and Germany were analysed.
      METHODS: Crude annual mortality rates were calculated and rates standardised by
      Poisson regression to allow assessment of changes over time and comparison
      between countries, sexes, and age groups. The relative trends in mortality from
      CFA and PIF were assessed by calculating the annual ratio of CFA to PIF deaths.
      RESULTS: Men were more likely than women to die from both CFA and PIF in all
      countries. The highest standardised CFA mortality rate occurred in England and
      Wales, and the lowest in Germany. Since 1979 mortality from CFA has increased in
      England and Wales, Australia, Scotland and Canada, but there was no trend in CFA
      mortality in New Zealand or Germany. In the USA mortality from CFA was low and
      has fallen. Mortality from PIF increased in all countries except New Zealand and
      Germany, and the highest PIF mortality, together with the greatest increase over
      time, was seen in the USA. Changes over time in the annual ratio of CFA to PIF
      deaths in all countries were small, implying that diagnostic transfer is not a
      major cause of the increasing CFA mortality. CONCLUSIONS: Mortality from CFA
      continues to increase in England and Wales and in many other countries.
      Diagnostic transfer from PIF does not appear to be a major cause of this.

PMID- 8882079
TI  - Accuracy of mortality data for interstitial lung diseases in New Mexico, USA.
AB  - BACKGROUND: The sensitivity and accuracy of death certificates and mortality data
      as sources of population based data on the occurrence of interstitial lung
      diseases has received limited attention. To determine the usefulness of these
      data sources, death certificates and mortality data from patients in New Mexico
      were examined. METHODS: Patients with an interstitial lung disease were
      identified from a population based registry. For subjects who had died,
      diagnostic information from their death certificates and from mortality data was
      compared with the clinical diagnoses made before death. RESULTS: Of 385 patients
      with a clinical diagnosis of an interstitial lung disease, 134 died between
      October 1988 and August 1994. Death certificates were obtained for 96% of these
      patients. An interstitial lung disease was listed somewhere on the death
      certificate for only 46% of the patients, and as an immediate cause of death for
      only 15%. For the patients with an interstitial lung disease listed somewhere on
      the death certificate the overall concordance between the diagnoses before death
      and those on the death certificate was 76%. Mortality data for the State of New
      Mexico showed a diagnosis of interstitial lung disease to be the assigned cause
      of death for only 22% of the patients. The overall agreement between the
      diagnoses made before death and those of the state mortality data was only 21%.
      CONCLUSIONS: These results suggest that death certificates and state mortality
      data are neither sensitive nor accurate for describing the occurrence of
      interstitial lung diseases. This finding may partly explain the apparently low
      mortality rates from idiopathic pulmonary fibrosis in the USA compared with other
      countries.

PMID- 8882080
TI  - Endocrine cells in tumour-bearing lungs.
AB  - BACKGROUND: When hormones are detected in the serum of patients with bronchial
      carcinoma they are generally considered to originate from the tumour, but this
      may be not the only explanation. Pulmonary endocrine cells proliferate in lungs
      affected by non-neoplastic disease and their products are often demonstrable in
      the serum. The aim of this study was to examine the pulmonary endocrine systems
      of a series of tumour-bearing lungs to see whether any changes in them could
      possibly account for raised levels of pulmonary peptides in the blood. METHODS:
      The morphology, number, distribution, and content of pulmonary endocrine cells in
      30 pairs of tumour-bearing lungs from patients coming to necropsy with bronchial
      carcinoma were examined. These features were related to the pathology of the
      tumour and to other pathological changes present in the lungs, and compared with
      pulmonary endocrine cells in 10 pairs of control lungs from patients without
      pulmonary disease. RESULTS: Increased numbers of endocrine cells, often in the
      form of large abnormal aggregates, were present in 17 pairs of tumour-bearing
      lungs where they were associated not with the tumour but with non-tumoral
      pathology, especially inflammation and changes associated with cardiac failure.
      Appropriate and inappropriate peptides were identified within them. CONCLUSION:
      The possibility is raised that, in some subjects with bronchial carcinoma who
      have raised serum hormone levels, the source of these substances might be the
      endocrine cells in the diseased lung around the tumour.

PMID- 8882081
TI  - Reduced beta adrenoceptor density in vivo in human lung tumours: a preliminary
      study with positron emission tomography.
AB  - BACKGROUND: Reduced beta adrenergic receptor density in tumours has been reported
      in previous in vitro studies. The aim of the present study was to assess whether
      this occurs in vivo. METHODS: Pulmonary beta adrenoceptors were imaged and
      quantified in vivo using positron emission tomography (PET) and the beta
      antagonist radioligand (S)-[11C]CGP-12177 in five men with lung tumours of mean
      age 58 years (range 42-68). The histology of the tumours was squamous cell
      carcinoma in two cases, adenocarcinoma in one, carcinoid tumour in one, and large
      cell carcinoma in one. The regional blood volume and extravascular tissue density
      were also measured using PET. Regions of interest were drawn for both non-tumour
      and tumour lung tissue. RESULTS: The mean (SD) blood volume was 0.142 (0.025)
      ml/ml in tumour regions and 0.108 (0.010) ml/ml in normal lung regions--a
      difference of 31%. Mean (SD) extravascular tissue density was 0.653 (0.133) g/ml
      in tumour regions, substantially higher than in normal lung regions (0.157
      (0.021) g/ml). On the contrary, beta receptor density was 5.1 (1.8) pmol/g in
      tumour regions, lower than the value of 9.9 (1.6) pmol/g found in adjacent normal
      lung--a difference of 48%. CONCLUSIONS: In vivo beta adrenoceptor density is
      reduced in human lung tumours.

PMID- 8882082
TI  - Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal
      Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis
      by western blotting and laser scanning densitometry.
AB  - BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas
      aeruginosa (a beta ab) are markers of the development of resistance of P
      aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and
      chronic lung infection. The role of these antibodies in patients with chronic
      lung infection with P aeruginosa was further investigated by correlating the a
      beta ab IgG subclasses with pulmonary function in patients with cystic fibrosis.
      METHODS: Immunoglobulin G (IgG) and IgG subclass a beta ab were investigated by
      western blotting and quantified by laser scanning densitometry. A longitudinal
      study on 43 consecutive patients with cystic fibrosis who developed chronic lung
      infection with P aeruginosa was performed. RESULTS: IgG subclass a beta ab
      appeared in all patients with chronic infection with P aeruginosa. Eleven years
      after the onset of infection all the patients had IgG1, 79% had IgG4, 56% IgG2,
      and only 16% of the patients had IgG3 a beta ab. The IgG1 and IgG4 a beta ab
      appeared first, and more than 50% of the patients were IgG1 and IgG4 a beta ab
      positive within 2-3 years of the onset of infection, but IgG2 positivity only
      appeared after seven years and IgG3 remained absent from most of the patients.
      The median a beta ab levels increased during chronic infection: 100-fold for
      IgG1, 22-fold for IgG2, and 45-fold for IgG4. A 16-fold increase in the IgG3 a
      beta ab levels was detected in the six patients who developed IgG3 a beta ab. In
      the first four years of the chronic infection the a beta ab titres were higher in
      patients with good lung function than in those with poor lung function.
      CONCLUSIONS: The association of a weak IgG3 and a strong IgG4 a beta ab response
      suggests that the contribution of a beta ab antibodies to lung diseases mediated
      by immune complexes might be less important than other antipseudomonal
      antibodies. A beneficial neutralising effect of the a beta ab antibodies on the
      antibiotic destroying enzymes may be an additional factor.

PMID- 8882083
TI  - Cytokines in bronchoalveolar lavage fluid in patients with high altitude
      pulmonary oedema at moderate altitude in Japan.
AB  - BACKGROUND: The precise mechanism of high altitude pulmonary oedema (HAPE)
      remains unclear. The purpose of this study was to evaluate the role of cytokines
      and P-selectin in the development of HAPE which occurred at moderate altitude in
      Japan. METHODS: The following cellular and biochemical markers and chemotactic
      cytokines were measured in the bronchoalveolar (BAL) fluid from four patients
      with HAPE at 2857-3180 m in the Japanese Alps: total proteins, albumin, lactate
      dehydrogenase (LDH), and interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor
      antagonist (ra), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, and the
      soluble form of P-selectin. RESULTS: At admission there were significant
      increases in the levels of total cells, especially macrophages and neutrophils,
      total protein, albumin and LDH when compared with 13 healthy individuals.
      Furthermore, the levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were also
      considerably increased but returned quickly to the normal ranges or were not
      detected after recovery. The levels of IL-1 alpha, IL-10, and P-selectin did not
      change. CONCLUSIONS: These results suggest that an inflammatory process almost
      identical with acute respiratory distress syndrome (ARDS) may occur in HAPE, but
      that these changes are transient and are not associated with any increase in P
      selectin levels in the BAL fluid.

PMID- 8882084
TI  - Comparison of soybean epidemic asthma and occupational asthma.

PMID- 8882085
TI  - The role of recombinant human DNase in the treatment of patients with cystic
      fibrosis: many promises, more problems.

PMID- 8882086
TI  - Techniques in mechanical ventilation: principles and practice.

PMID- 8882087
TI  - Pulmonary hypertension: NO therapy?
AB  - Endothelium-derived nitric oxide (NO) is a powerful pulmonary vasodilator which
      also prevents adhesion and aggregation of platelets, controls growth of smooth
      muscle, and influences the expression of growth promoting and vasoactive
      substances. Impaired endothelial NO production contributes to pulmonary
      vasoconstriction and vascular remodelling in several forms of pulmonary
      hypertension. Exogenous NO gas delivered via the airspaces is a selective
      pulmonary vasodilator now used as treatment in various lung disorders.

PMID- 8882088
TI  - Lymphangiomatosis presenting with bronchial cast formation.
AB  - Lymphangiomatosis is a rare disorder of the lymphatic system that is known to
      cause chylothorax. Chyloptysis may occur but chylous bronchial cast formation is
      rare. A case is reported of lymphangiomatosis in a 34 year old woman whose
      initial manifestation was cough productive of bronchial casts. Two years later
      the patient developed a chylothorax. Ligation of the thoracic duct through a low
      thoracotomy was curative.

PMID- 8882089
TI  - Generalised lymphangiectasia: pulmonary presentation in an adult.
AB  - A 25 year old man presented with dyspnoea and was found to have generalised, but
      predominantly pulmonary, lymphangiectasis without gastrointestinal symptoms. This
      is an unusual presentation of a disorder previously diagnosed only in childhood.

PMID- 8882090
TI  - Bronchoalveolar lavage with trypsin in pulmonary alveolar proteinosis.
AB  - Two cases of pulmonary alveolar proteinosis were treated with bronchoalveolar
      lavage (BAL) via a fibreoptic bronchoscope. Additional clinical improvement was
      seen when trypsin was added to the lavage fluid. Analysis of effluents in the BAL
      fluid showed marked reduction of protein constituents with clinical improvement
      after treatment with trypsin in the lavage. BAL with trypsin was well tolerated.

PMID- 8882091
TI  - Nosocomial pneumonia during mechanical ventilation.

PMID- 8882092
TI  - Silica exposure and risk of lung cancer.

PMID- 8882094
TI  - Students' perception of occupational medicine.

PMID- 8882093
TI  - Mesothelioma: An unwarranted causal model.

PMID- 8882095
TI  - The disabled, the disallowed, the disaffected and the disavowed.

PMID- 8882096
TI  - The effects of chronic industrial noise exposure on urinary cortisol, fatigue and
      irritability: a controlled field experiment.
AB  - This quasiexperimental field study explored the effect of noise attenuation on
      urinary cortisol excretion (sampled three times, at 6:30 and 10:30 AM and 1:30
      PM) and reported fatigue and postwork irritability among 35 healthy industrial
      workers chronically exposed to high ambient noise levels (> 85 dB [A]) without
      using ear protectors. The results indicated that under conditions of chronic
      noise exposure the cortisol level at the end of the workshift was high and almost
      reached the morning level. This elevation in cortisol excretion was accompanied
      by high levels of accumulated fatigue and postwork irritability. Attenuating the
      noise reaching the eardrum by 30 to 33 dB, by fitting the same workers with
      earmuffs for a period of 7 working days, resulted in a significant improvement in
      both psychological and physiological stress reactions. Besides decreasing noise
      intensity, no other changes were made, either to ongoing work activities or to
      the other characteristics of the ambient noise. The cortisol level declined
      steadily during the workshift and exhibited the normal cortisol diurnal rhythm.
      At the end of the workshift, this level was significantly lower (P < .05) than
      that observed under the chronic noise-exposure condition. There was also a
      concomitant reduction in reported fatigue (P < .05) and postwork irritability (P
      < .01). These findings demonstrate the "net" contribution of ambient noise to
      elevating stress reactions to regular work demands.

PMID- 8882097
TI  - Health care worker exposure to aerosolized ribavirin: biological and air
      monitoring.
AB  - Aerosolized ribavirin is administered frequently to treat severe respiratory
      syncytial virus infections. The drug's potential reproductive effects in
      occupationally exposed workers remains a concern among health care workers. In
      this evaluation, we measured urinary ribavirin concentrations in occupationally
      exposed health care workers. Ribavirin was detected in 16 of 26 (62%) post-work
      shift urine samples that had been provided by nurses, and in five of 22 (23%)
      post-work-shift urine samples that had been provided by respiratory therapists
      (range, < 0.01 to 0.22 mumol/L). We also measured airborne ribavirin
      concentrations in the personal breathing zones of nurses. Ventilators and other
      administration units that were enclosed by an aerosol containment tent produced
      significantly lower airborne ribavirin exposures than administration units
      without a containment tent did (range, < 2.5 to 78 micrograms/m3). On the basis
      of this and other evaluations of airborne ribavirin concentrations, we recommend
      using aerosol containment systems with all types of ribavirin administration
      units except mechanical ventilators.

PMID- 8882098
TI  - Explant culture, immunofluorescence and electron-microscopic study of flexor
      retinaculum in carpal tunnel syndrome.
AB  - Although flexor-retinaculum (FR) release provides dramatic relief from carpal
      tunnel syndrome (CTS), the role of this ligament in CTS is not well understood.
      We have adopted a unique approach to study the cellular pathogenesis of CTS by
      establishing a method for the culture of cells of FR from subjects with and
      without CTS. The cultured cells were characterized by light, immunofluorescence,
      electron microscopy, Western blot analysis, and growth studies. Two main
      differences between the CTS and control cells included a faster growth rate and
      an altered fine morphology that reveals the contractile nature of the CTS cells.
      It is possible that the presence of these contractile cells in FR is responsible
      for increasing the contractility of the FR, leading to a decrease in the volume
      of the carpal tunnel, thus exerting pressure on the median nerve and triggering
      CTS.

PMID- 8882099
TI  - Mortality patterns among Vietnam veterans: a 24-year retrospective analysis.
AB  - The mortality experience of 33,833 US Army and Marine Corps Vietnam veterans who
      died during 1965-1988 was compared with that of 36,797 deceased non-Vietnam
      veterans using proportionate mortality ratios (PMRs). Military service
      information was abstracted from military personnel records and cause of death
      information recorded from death certificates. Army Vietnam veterans had
      statistically significant excesses of deaths from laryngeal cancer (PMR = 1.38)
      and lung cancer (PMR = 1.08). There was an excess of external causes (PMR =
      1.03), including motor vehicle accidents (PMR = 1.03) and accidental poisonings
      (PMR = 1.17). In contrast to Army Vietnam veterans, the results for Marine
      Vietnam veterans varied according to the referent population used. When compared
      with non-Vietnam veterans, Marine Vietnam veterans had significantly elevated
      PMRs for lung cancer (PMR = 1.17) and skin cancer (PMR = 1.33). There was also a
      significant excess of external causes of death (PMR = 1.06), accidental
      poisonings (PMR = 1.19), and homicides (PMR = 1.16) compared with all non-Vietnam
      veterans.

PMID- 8882100
TI  - Improvement in lung function measurements using a flow spirometer that emphasizes
      computer assessment of test quality.
AB  - We compared retrospective measurements of lung function from 101 steel workers
      using a commercially available spirometer to prospective lung function
      measurements performed, on average, 1.3 years later, with a newly developed
      spirometer. This spirometer was designed and developed to incorporate technology
      that provides immediate feedback on the quantitative and qualitative aspects of
      each forced expiratory effort. Of the 101 workers, 82 who had spirometry
      performed with each spirometer had at least two acceptable curves, and 51 workers
      tested with each spirometer had curves that met all American Thoracic Society
      (ATS) criteria for spirometry. No group showed the anticipated decline in forced
      expiratory volume in 1 second (FEV1) over time. The results showed an increased
      number of curves meeting ATS acceptability and reproducibility criteria, and a
      statistically significant increase in the FVC in all groups, and an increase in
      the FEV1 in the group encompassing all workers. Use of technology that
      strengthens the interaction between the spirometry technician, the data available
      to the technician on the computer, and the participant appears to represent true
      underlying lung function more accurately. Such an approach to the collection of
      lung function data should be considered by those evaluating spirometers for
      implementation in the workplace or pulmonary function laboratory as well as by
      those planning future spirometer development.

PMID- 8882101
TI  - A graduate course in work site health promotion for occupational health
      practitioners.
AB  - This paper describes the rationale, teaching strategies, outcomes, and a 6-month
      follow-up of an academic course in work site health promotion, in which 35
      occupational health practitioners participated. The one-semester course was part
      of the Masters in Science program in occupational health at the Tel-Aviv
      University Medical School. The primary goals of the study were to teach the
      theoretical bases of work site health promotion and their application to specific
      health needs, and to train better role models for employees. The primary teaching
      strategies were: (1) facilitation of experiential learning, by encouraging
      students to undergo health screening and then engage in a personal health
      promotion plan; (2) use of health promotion experts as guest teachers; and (3) an
      increase in formal knowledge through formal lectures and background reading. At
      the time of follow-up, most of the students were still adhering to their plans
      and maintaining much of their health promotion achievements. Additional outcomes
      included increased awareness of health risks and health promotion issues, and
      positions as role models in the private and professional domains. The primary
      barrier to adherence was low frustration tolerance, which can be regarded as the
      major challenge to health promotion programs and courses. It is suggested that
      the course format is an effective means of educating health promoters.

PMID- 8882102
TI  - Tobacco, caffeine, alcohol, and carpal tunnel syndrome in American industry. A
      cross-sectional study of 1464 workers.
AB  - We investigated the effects of three legal drugs (tobacco, caffeine, and alcohol)
      on the prevalence of carpal tunnel syndrome (CTS) confirmed by nerve conduction
      studies (definite CTS) in two groups of American industrial workers: 656
      nonclaimant workers and 808 working patients referred for upper extremity
      symptoms. Comparing workers with definite CTS to workers without definite CTS
      revealed 26% greater current use of tobacco, 19% greater lifetime use of tobacco,
      5% greater current use of caffeine, 14% lesser current use of alcohol, and 75%
      greater history of alcohol abuse in the workers with definite CTS. All these
      differences were statistically significant. Those who currently used alcohol but
      not tobacco or caffeine were at the lowest risk for slowing, symptoms, and
      definite CTS. Those who currently used caffeine alone or in combination with
      tobacco were at the highest risk. In female workers, current smoking, current
      caffeine use, and current coffee consumption independently predicted 5.0% of the
      explainable risk for definite CTS. In male workers, history of alcohol abuse and
      current beer consumption independently predicted 3.0% of the explainable risk for
      definite CTS. Prevalence of slowing, symptoms, and definite CTS in 12 specific
      job categories correlated directly with current tobacco use. We conclude that the
      use of legal drugs affects the prevalence of median nerve slowing, symptoms, and
      carpal tunnel syndrome, but the effects of the drugs independently explain only a
      small portion of the total risk. Nevertheless, legal drug use or abuse may serve
      as a marker for increased CTS risk.

PMID- 8882103
TI  - A twenty year (1971-1990) review of tracheostomies in a major paediatric
      hospital.
AB  - Changing trends in the indications for paediatric tracheostomies, with decreasing
      numbers of tracheostomies being performed, have been reported in the literature.
      In a retrospective analysis of the period 1971 to 1990 the experience of
      tracheostomies in children under the age of 15 at Our Lady's Hospital (Dublin) is
      reviewed. Only 29 tracheostomies were performed during this time with an increase
      in numbers (90%) performed during the second 10 year period. The major underlying
      indication for tracheostomy in both 10 year periods was for the management of an
      airway problem secondary to congenital abnormalities (65%). In 14 children the
      operation was performed during the first year of life. However, while 90% of the
      children were under the age of one in the period 1971-1980 this fell to 26%
      during 1981-1990. Complications occurred in 41% overall, however, in the under 1
      year old group 64% developed complications. There were no deaths as a direct
      result of the tracheostomy or its complications, but six children died because of
      the severity of the underlying disease. The average length of time before
      decannulation was 2.1 years, with decannulation difficulties occurring
      infrequently (11%).

PMID- 8882104
TI  - Selection of pediatric patients for use of the Passy-Muir valve for speech
      production.
AB  - A potential side effect of tracheotomy in the pediatric population is poor speech
      development. It has been well documented that children with tracheotomies have
      delays in expressive and receptive language out of proportion to the child's
      degree of intellectual functioning. While numerous methods of augmentative
      devices have been proposed, none are ideal for the child with a tracheotomy. Of
      the choices available, the Passy-Muir valve is best suited for use in the
      pediatric population. We present a method of selection of patients for Passy-Muir
      valve placement currently in use at Blythedale Children's Hospital. The criteria
      employed include measurement of trans-tracheal pressures. This has not previously
      been presented in the literature, but has been found to be of significant value
      in determining who will benefit most from Passy-Muir valve placement.

PMID- 8882105
TI  - Topical lidocaine for postoperative analgesia following myringotomy and tube
      placement.
AB  - One of the most frequently performed surgical procedures in pediatrics is
      myringotomy and tube placement. Analgesia is often difficult to achieve and
      children may be uncontrollable, distressing both parents and nursing staff. We
      designed this investigation to determine if topical lidocaine instilled in the
      ear canal after myringotomy and tube placement could improve postoperative
      analgesia. This prospective, randomized, double-blind clinical trial compared
      topical 4% lidocaine combined with antibiotic drops to placebo and antibiotic
      drops placed in the external auditory canal following completion of myringotomy
      and tube placement. One hundred twenty-two ASA class I or II patients were
      enrolled and completed this investigation. Primary outcome measure was relief of
      pain based on pain scores and the need for acetaminophen. Patients who received
      4% lidocaine with gentamicin had better pain scores (2.81; P = 0.002) than those
      receiving placebo (4.77). Twenty-seven patients (45%) in the control group
      received acetaminophen for treatment of postoperative pain compared to eight
      (13%) in the lidocaine group (P < 0.001). No reports or complaints of vertigo or
      tinnitus were noted in any patient. The application of 4% lidocaine in antibiotic
      drops significantly improves postoperative analgesia in patients undergoing
      myringotomy and tube insertion under general anesthesia. Utilizing this technique
      should help improve analgesia, specifically in the early postoperative period,
      and decrease the presence of stress following surgery.

PMID- 8882106
TI  - Early adenotonsillectomy for relief of acute upper airway obstruction due to
      acute tonsillitis in children.
AB  - Early adenotonsillectomy (TA) for acute upper airway obstruction precipitated by
      acute tonsillitis was performed in 17 children admitted to the Royal Childrens
      Hospital over a 15 year period. The age ranged from 13 to 83 months (mean 37
      months) and surgery was performed from 1 to 11 days (mean 5.8 days) following
      admission. One child who underwent surgery within 24 h of admission had an
      intraoperative blood loss of 250 ml requiring transfusion, but there were no
      cases of post operative hemorrhage. Airway obstruction was relieved by surgery in
      all cases and patients were discharged 1 to 6 days (mean 2.4 days) later. Early
      TA should be considered for relief of upper airway obstruction due to acute
      tonsillitis after an initial 24 h of intravenous antibiotic therapy.

PMID- 8882107
TI  - Role of cesarean section in prevention of recurrent respiratory papillomatosis-
      is there one?
AB  - Recurrent respiratory papillomatosis (RRP) is a benign yet aggressive neoplasm
      that produces considerable morbidity in children. Previous studies have linked
      RRP in children to mothers with genital tract human papillomavirus infections
      (HPV). Risk factors for vertical transmission have not been well identified.
      Controversy exists among obstetricians and otolaryngologists regarding the role
      of cesarean section in preventing the transmission of HPV disease from mother to
      child. We address this issue by presenting the results of a national survey of
      otolaryngologists, the American College of Obstetrics and Gynecology position
      statement, the relevant literature regarding the association between RRP and
      maternal HPV, and the proposed mechanisms for HPV transmission at birth. We
      postulate a very limited role for cesarean section in preventing transmission of
      RRP, given our present knowledge of this disease.

PMID- 8882108
TI  - Oral palatine ulcers of a traumatic nature in infants: Bednar's aphthae.
AB  - The authors present five cases of large palatine ulcers of a traumatic nature in
      infants, with duration from two weeks to four months. Causal diagnosis was
      difficult at first until the possibility of trauma caused by non-orthodontic
      nipples (all cases) and dummies (4)--Bednar's aphthae--was considered. Other
      problems related to sucking were observed: a horizontal position for nursing
      (all) and very narrow nipple hole (4). The infants' mothers were advised to
      enlarge the orifice in the nipple and correct the position for nursing (3 cases)
      and, in addition, to suspend use of a dummy (1 case) and discontinue use of a
      bottle and dummy (1 case). All of the ulcers healed within a period from one to
      four weeks. Small scars remained in two of the children.

PMID- 8882109
TI  - The nasal volume of children as measured by Manometric Rhinometry.
AB  - A new method of measuring nasal volume has been developed called 'Manometric
      Rhinometry'. We describe the principle behind its use and present the results of
      measuring two groups of normal children aged 4-10. The total volume of the nasal
      cavity, paranasal sinuses and postnasal space in these children averaged 81 ml in
      4-year olds and 140 ml in 10-year olds when measured using an open cell foam
      plug. Where a rigid nasal tip was used the volume averaged 67 ml in 4-year olds
      rising to 99 ml in 8-year olds. Correlation with age, weight, height and head
      circumference showed the greatest correlation with height (r = 0.66). Multiple
      regression analysis did not add further explanatory power.

PMID- 8882110
TI  - Acoustic trauma caused by lightning.
AB  - Lesions produced by exposure to noise are frequent in everyday life. Injuries may
      be found in all systems of the human body, from the digestive to the endocrine,
      from the cardiovascular to the nervous system. Many organs may be damaged, the
      ear being one of them. It is known that noise produced by factories, airports,
      musical instruments and even toys can cause auditory loss. Noises in nature can
      also cause acoustic trauma. This report is the case history of acoustic trauma
      caused by lightning. The patient was studied with CAT scan, electroencephalogram,
      and brain mapping, impedance audiometry with tympanogram and acoustic reflex,
      audiometry and evoked otoacoustics emissions: distortion products and transients.

PMID- 8882111
TI  - Nager acrofacial dysostosis: management of a difficult airway.
AB  - Nager acrofacial dysostosis, first described by Nager and deReynier in 1948, is a
      rare syndrome characterized by mandibulofacial dysostosis with associated radial
      defects. The facial features include downward slanting palpebral fissures, absent
      eyelashes in the medial third of the lower lids, mandibular and malar hypoplasia,
      dysplastic ears with conductive deafness, and variable degrees of palatal
      clefting. Upper limb malformation is a constant feature of Nager syndrome and
      ranges from thumb hypoplasia to absence of the radial ray. The maxillo-mandibular
      hypoplasia and associated retroplaced tongue set the stage for early and
      significant upper airway obstruction. The craniofacial anomalies and associated
      trismus make emergent airway intubation challenging. We present a case of Nager
      syndrome with life threatening airway obstruction unresponsive to conservative
      management. This case and a review of the literature emphasize the importance of
      early tracheotomy for these patients.

PMID- 8882112
TI  - Accidents related to manure in eastern Switzerland: an epidemiological study.
AB  - OBJECTIVES: Liquid manure systems and manure pits are major hazards in the
      agricultural workplace. The incidence of accidents related to manure is unknown.
      The objective of this study was to survey the liquid manure facilities of farms
      in eastern Switzerland and find the incidence of accidents related to manure in
      the region. METHODS: Retrospective cohort study and cross sectional survey of 210
      farms in eastern Switzerland. RESULTS: The incidence of accidents related to
      manure was found to be 10.4/1000 person-years. Most accidents were categorised as
      minor--that is, had a benign outcome for the people involved or involved animals
      only. One in 33 of the farms surveyed was the scene of an accident related to
      manure each year. CONCLUSIONS: The medical literature on accidents related to
      manure mostly reports accidents with catastrophic outcomes. This study shows that
      this type of accident is only the tip of the iceberg. Most of the accidents
      reported in this study belong to a category that has hitherto been un-noticed and
      unreported. The term "accident related to manure" covers a broad range of events,
      and those resulting in serious human illness or death represent only a small part
      of this spectrum. A wide variety of liquid manure systems were found on the farms
      surveyed. Very few liquid manure facilities conformed to published safety
      standards.

PMID- 8882113
TI  - Immunological changes among farmers exposed to phenoxy herbicides: preliminary
      observations.
AB  - OBJECTIVES: To evaluate short term immunological changes after agricultural
      exposure to commercial formulations of chlorophenoxy herbicides. METHODS: Blood
      samples were collected from 10 farmers within seven days before exposure, one to
      12 days after exposure, and again 50 to 70 days after exposure. Whole blood was
      used to count lymphocyte subsets with monoclonal antibodies. Peripheral blood
      mononuclear (PBM) cells were used to measure natural killer (NK) cell activity
      and lymphocyte response to mitogenic stimulations. Values before exposure were
      used as reference. RESULTS: In comparison with concentrations before exposure, a
      significant reduction was found one to 12 days after exposure in the following
      variables (P < 0.05): circulating helper (CD4) and suppressor T cells (CD8), CD8
      dim, cytotoxic T lymphocytes (CTL), natural killer cells (NK), and CD8 cells
      expressing the surface antigens HLA-DR (CD8-DR), and lymphoproliferative response
      to mitogen stimulations. All immunological values found 50-70 days after exposure
      were comparable with concentrations before exposure, but mitogenic proliferative
      responses of lymphocytes were still significantly decreased. CONCLUSIONS:
      According to our data agricultural exposure to commercial 2,4
      dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA)
      formulations may exert short term immunosuppressive effects. Further studies
      should clarify whether the immunological changes found may have health
      implications and can specifically contribute to cancer aetiology.

PMID- 8882114
TI  - Acute effects of exposure to air contaminants in a sawmill on healthy volunteers.
AB  - OBJECTIVES: To study whether air contaminants in sawmills can induce acute
      changes in the upper and lower airways of previously non-exposed subjects.
      METHODS: Nineteen healthy volunteers were examined to find the concentration of
      interleukin 6 (IL-6) in nasal lavage fluid and lung function before and after
      five hour exposure to dusts and fumes generated in a sawmill where timber from
      Scots pine was sawed. When exposed, the subjects had respirators with and without
      a particle filter. RESULTS: The median for daily time weighted average
      concentration of total dust for subjects with respirators without a filter was
      0.13 mg/m3, which was significantly higher than the median of 0.04 mg/m3 for
      subjects who had respirators with a filter. The median for the concentration of
      IL-6 in the nasal lavage fluid increased after exposure from 0.5 to 5.9 pg/ml in
      subjects with respirators without a particle filter (P < 0.05). The increase of
      the concentration of IL-6 was significantly correlated with the dust
      concentration. A decrease in transfer factor of the lung was significantly
      correlated with daily time weighted average concentrations of terpenes.
      CONCLUSION: The findings suggest that healthy volunteers, exposed to air
      contaminants in a sawmill, show a slight inflammatory reaction. Also, the results
      of the study indicate the importance of decreasing the concentrations of wood
      dust in the work environment.

PMID- 8882115
TI  - Interferences of urinary tract infection in the measurement of urinary nitrous
      oxide.
AB  - OBJECTIVES: To investigate the effective role of micro-organisms in producing
      N2O. METHODS: The N2O in either urine samples inoculated with 24 microbial
      strains or urine samples from patients with urinary tract infections were
      measured. RESULTS: Gram negative bacilli generally produced high amounts of
      nitrous oxide (N2O), whereas Gram positive cocci and yeasts did not. The
      production of N2O depends on the incubation time and follows exponential
      kinetics, reaching a plateau at 48 hours. Furthermore, the results of
      urinocultures agreed well with N2O concentrations found in urine samples: samples
      negative for bacteria were found to contain very low concentrations of N2O
      whereas those positive--for example, for Enterobacteriaceae--gave highest N2O
      values. CONCLUSION: The urinary tract infections caused by Gram negative bacilli
      are important confounding factors in biological monitoring practices of exposure
      to inhalation anaesthetics. The current methods adopted to avoid these factors
      (urine acidification, storage of samples at 4 degrees C) are not good enough
      because of the relative acid tolerance of some strains and the production of N2O
      directly into the bladder.

PMID- 8882117
TI  - Comparison of average estimated metabolic rates for styrene in previously exposed
      and unexposed groups with pharmacokinetic modelling.
AB  - OBJECTIVE: To understand whether previous styrene exposure increases the human
      liver's ability to convert styrene into styrene oxide. METHODS: The hypothesis
      was tested that the average linear metabolic rate constant kappa was the same in
      both exposed and unexposed groups, when the exposed group comprised people with a
      history of styrene exposure and the unexposed group had no exposure. In an
      experimental chamber, these two groups of subjects were exposed to a
      concentration of 80 ppm styrene for two hours. A three compartment
      pharmacokinetic model was used to define kappa. Based on large sample theory, the
      comparison of estimated mean values of kappa in the exposed and unexposed groups
      was shown to be equivalent to a comparison of the estimated mean values of the
      hepatic clearance X in the two groups. A method was developed to estimate X for
      each subject in both groups from the subject's height, weight, and estimated
      asymptotic styrene decay constant alpha. Here, alpha was estimated individually
      from observed blood concentrations over time when sufficient time had elapsed
      after the controlled exposure. RESULTS: The proposed methodology of comparing the
      estimated mean values of kappa in exposed and unexposed groups reduced the number
      of specific physiological variables involved to three, all of which were
      estimable from data based on simple direct measurements. In contrast, other
      methods based on pharmacokinetic models usually involved many variables that were
      non-estimable on an individual basis. Consequently, statistical comparisons were
      impossible. These methods were applied to analyse previously published data on
      the time course of styrene concentrations in arterial blood of subjects in both
      exposed and unexposed groups. A Wilcoxon non-parametric rank sum test with the
      individually estimated X values was used, and no significant difference in the
      means of X in the two groups was found. CONCLUSION: The linear metabolic rate
      constant kappa for humans is probably not altered by previous exposure to
      styrene. This result is in agreement with some experimental studies on animals.
      However, in the data analysis, it was noted that the number of subjects in each
      group was small (6-7) and that the styrene concentration data did not exactly
      reflect true behaviour of asymptotic decay. Further studies are still needed to
      draw more definitive conclusions.

PMID- 8882116
TI  - Urinary alkoxyacetic acids and renal effects of exposure to ethylene glycol
      ethers.
AB  - OBJECTIVES: Ethylene glycol ethers and their acetates are widely used in
      industry, because of their hydrophilic and simultaneously lipophilic properties.
      Ethylene glycol ethers and their acetates are mainly metabolised to alkoxyacetic
      acids, but there is also a minor pathway through ethylene glycol to oxalic acid.
      The main pathway of ethylene glycol ethers is associated with significant
      clinical or experimental health effects and the minor pathway is also interesting
      because formation of urinary stones depends principally upon the urinary
      concentration of oxalate and calcium. METHODS: Excretion of alkoxyacetic and
      oxalic acids was examined among silkscreen printers for an entire working week.
      The aim of the study was to evaluate alkoxyacetic acids as early indicators of
      exposure to glycol ethers and to evaluate their toxicity to kidneys. The load of
      alkoxyacetic and oxalic acids was compared with the excretion of calcium,
      chloride, ammonia, and glycosaminoglycans (GAG). Morning urine was chosen for the
      main analysis, as the overall metabolite, ethoxyacetic acid (EAA), has a long
      elimination time from the body. RESULTS: The excretion of calcium increased
      according to the urinary alkoxyacetic acid load. The excretion of ammonia and
      chloride was higher among the exposed workers than among the controls. The
      highest urinary alkoxyacetic acid load was also associated with increased
      excretion of GAG, which may reflect the toxicity of metabolites of ethylene
      glycol ether. The excretion of GAG correlated positively with that of calcium in
      the printers with highest exposure. The tendency to form urinary stones was 2.4
      fold higher among silkscreen printers than among office workers. CONCLUSION: On
      the basis of renal effects our study indicates the need for establishing a new
      biological exposure limit before a workshift that is clearly below 100 mmol
      ethoxyacetic acids per mol creatinine in morning urine of people occupationally
      exposed to ethylene glycol ethers.

PMID- 8882118
TI  - Cause specific mortality and cancer incidence among employees exposed to 2,3,7,8
      TCDD after a 1953 reactor accident.
AB  - OBJECTIVE: To evaluate the long term health consequences of past occupational
      exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). METHODS: Cancer incidence
      and cause specific mortality were examined up to and including 1992 in a group of
      243 men with external comparisons and internal dose-response analyses. Model
      based estimates of TCDD dose (expressed in micrograms/kg body weight) were
      developed for all cohort members with an approach that incorporated detailed
      accounts of each employee's work activities, analyses of TCDD in blood lipid of
      138 employees, and internally derived estimates of elimination rates of TCDD.
      RESULTS: The estimated dose of TCDD for 135 men was > or = 0.1 microgram/kg body
      weight and for 69 men > or = 1 microgram/kg body weight. Increased cancer risk
      ratios were found with higher doses of TCDD and longer interval since first
      exposure for all sites combined and digestive and respiratory cancers in
      particular. Within the high dose group (> or = 1 microgram/kg body weight), total
      cancer mortality was increased > or = 20 years after first exposure (13 cases,
      standardised mortality ratio (SMR) 1.97, 95% confidence interval (95% CI) 1.05
      3.36) as was respiratory cancer (six cases, SMR 3.06; 95% CI 1.12-6.66). Among
      current cigarette smokers, 12 cancer deaths occurred in the high dose group (SMR
      3.42, 95% CI 1.77-5.97) compared with seven deaths at lower doses of TCDD (SMR
      1.29, 95% CI 0.52-2.66). Regression analyses based on the Cox's proportional
      hazards model provided further evidence of a relation between cumulative dose of
      TCDD and occurrence of both overall and digestive cancer. No evidence of an
      effect of TCDD on overall mortality or deaths due to circulatory disease was
      found and no cases of non-Hodgkin's lymphoma or soft tissue sarcoma have been
      found to date. CONCLUSIONS: Our findings are consistent with a carcinogenic
      effect induced by TCDD at doses > or = 1 microgram/kg body weight. With such a
      small cohort, the risk estimates are not very stable and could be affected by
      selection and confounding.

PMID- 8882119
TI  - Mortality among chemical workers in a factory where formaldehyde was used.
AB  - OBJECTIVES: An independent and updated historical cohort mortality study was
      conducted among chemical plant workers to investigate further an association
      between exposures to formaldehyde and particulates and cancers of the nasopharynx
      and lung reported in an earlier National Cancer Institute study of the same
      plant. METHODS: Subjects were 7359 workers who were first employed between 1941
      and 1984 in a factory in Wallingford, Connecticut where formaldehyde was used.
      Vital status was determined on 31 December 1984 for 96% of the cohort and death
      certificates were obtained for 93% of 1531 known deaths. Exposures of individual
      workers were estimated quantitatively for formaldehyde, product particulates, and
      non-product particulates, and qualitatively for pigment. Statistical analyses
      focused on 6039 white men in 1945-84. Cohort data that could not have been
      included in the National Cancer Institute study were also analysed separately.
      RESULTS: Mortality among long term workers (employed > or = 1 y) was generally
      similar to or more favourable than that of the general population, and there was
      little evidence of a relation between either rates of lung cancer or standardised
      mortality ratios (SMRs) and several measures of exposure to formaldehyde,
      particulates, and pigment. For several causes including lung cancer, death rates
      among short term workers (employed < 1 y) were significantly increased. Short
      term workers did not seem to differ from long term workers for the exposures
      considered. Among all white men, a significant SMR of 550 (local comparison) for
      nasopharyngeal cancer (NPC) was based on the same four index cases identified in
      the earlier study of this plant. Only one case of nasopharyngeal cancer had any
      appreciable exposure to formaldehyde. No new cases of nasopharyngeal cancers were
      found among the cohort data that could not have been included in the National
      Cancer Institute study--that is, extended observation time and additional study
      members. CONCLUSIONS: Among workers employed for at least one year, this study
      provides little evidence that the risk of lung cancer is associated with exposure
      to formaldehyde alone or in combination with particulates or pigment. The
      significant increases in both the rates and SMRs for lung cancer seem to be
      primarily a phenomenon of short term workers, but the possibility remains that
      unmeasured occupational or non-occupational factors may have played a part.

PMID- 8882120
TI  - Lung cinescintigraphy in the dynamic assessment of ventilation and mucociliary
      clearance of asbestos cement workers.
AB  - OBJECTIVES: To verify in vivo whether lung cinescintigraphy confirms the effect
      of asbestos on the patency of the smallest airways and on the efficiency of
      mucociliary clearance in asbestos cement workers. METHODS: 39 male subjects were
      examined: 30 asbestos cement workers and nine workers never exposed to
      occupational respiratory irritants. All subjects had a chest radiograph
      (International Labour Organisation (ILO) 1980); standard questionnaire on chronic
      bronchitis; spirometry; arterial blood gas analysis; carbon monoxide transfer
      factor (TLcosb); pulmonary O2 and CO2 ductances (DuO2, DuCO2); electrocardiogram;
      and lung cinescintigraphy after radioaerosol inhalation for the measurement of
      mucociliary clearance time in vivo in the smallest ciliated airways and for the
      assessment of radioaerosol deposition in alveoli (alveolar deposition index).
      RESULTS: Apart from nine non-exposed subjects, the 30 asbestos cement workers
      were so classified on the basis of chest radiography: nine of them as healthy
      exposed, 10 with pleural plaques, and 11 with asbestosis. The four groups had
      similar ages, work seniority, and smoking habits. Exercise dyspnoea was
      significantly more frequent in asbestos cement workers. Lung function variables
      of workers with effects related to asbestos were significantly lower than the
      other two groups. The PaO2, TLcOsb and DuO2 mean values were significantly lower
      in exposed workers than non-exposed. The mean PacO2 value was significantly
      higher in the asbestosis group than in the other three groups. Workers with
      effects related to asbestos showed a significantly lower alveolar deposition
      index and a significantly higher mucociliary clearance time than the other two
      groups. Subjects with asbestosis showed similar differences from those with
      pleural plaques. CONCLUSIONS: Lung cinescintigraphy confirms in vivo the effects
      of asbestos on bronchiolar and alveolar patency and on efficiency of mucociliary
      clearance in the smallest ciliated airways. Finally, lung cinescintigraphic
      variables are able to discriminate workers with asbestosis from those with
      pleural plaques.

PMID- 8882121
TI  - Work related risk factors for musculoskeletal complaints in the nursing
      profession: results of a questionnaire survey.
AB  - OBJECTIVES: To determine the prevalence of musculoskeletal complaints of the
      back, arms or neck, and legs among nurses, and to investigate the relation
      between these complaints and various work related and personal variables.
      METHODS: A questionnaire survey was carried out in four nursing homes in The
      Netherlands. RESULTS: The response was 95% and resulted in 846 completed
      questionnaires. It was found that a large proportion of the subjects regularly
      had back complaints (36%) but also had arm or neck (30%) and leg complaints
      (16%). Almost all respondents (89%) considered nursing work as physically
      strenuous. Most of them complained of working under time pressure (69%),
      increased work pressure (70%), and having no opportunity to take a break from the
      work (70%). The physical variables which seem to trouble the subjects most were
      lifting (65%), working in awkward postures (47%), and stooping (34%). Moreover,
      53% of the subjects responded that the ergonomic lay out of the ward was
      disagreeable. Most of the work related variables under study seemed to be
      associated with musculoskeletal complaints. For all types of complaints the
      strongest associations were found with having to lift heavy loads. Apart from
      physical stress various aspects of work pressure showed strong associations with
      the occurrence of musculoskeletal complaints. The variables on the ergonomy of
      the ward showed less clear associations with musculoskeletal complaints than were
      found for physical stress and work pressure. CONCLUSIONS: From these results it
      may be concluded that future research of health risks of nursing work should have
      a wider focus than the relation between physical workload and low back pain.

PMID- 8882122
TI  - Research priorities in occupational medicine: a survey of United Kingdom
      personnel managers.
AB  - A Delphi survey was carried out in an attempt to identify areas of priority in
      occupational health that should be targeted by research. Previously 53
      occupational physicians identified and ranked these areas. These were then
      assessed by personel managers. There was considerable agreement on priorities
      between the two groups with musculoskeletal disorders and stress securing the
      highest ranking.

PMID- 8882123
TI  - Reanalysis of mortality from lung cancer among diatomaceous earth industry
      workers, with consideration of potential confounding by asbestos exposure.
AB  - OBJECTIVE: To evaluate the potential for confounding from asbestos exposure,
      primarily chrysotile, on the relation between crystalline silica and mortality
      from lung cancer among diatomaceous earth (diatomite) workers. METHODS: A
      reanalysis of a cohort mortality study of diatomite workers was performed to take
      into account quantitative estimates of asbestos exposure. The reanalysis was
      limited to a subset of the original cohort, comprising 2266 white men for whom
      asbestos exposure could be reconstructed with greatest confidence. Comparisons
      between mortality from lung cancer (standardised mortality ratios (SMR)) were
      made between rates for 1942-87 for United States white men, and workers cross
      classified according to cumulative exposures to crystalline silica and asbestos.
      Comparisons of internal rates, involving Poisson regression modeling, were
      conducted for exposure to crystalline silica, with and without adjustment for
      asbestos exposure. Exposures were lagged by 15 years to take into account disease
      latency. RESULTS: There was an overall excess of lung cancer (SMR 1.41; 52
      observed). The SMRs for four categories of increasing crystalline silica among
      the workers not exposed to asbestos were 1.13, 0.87, 2.14, 2.00. An SMR of 8.31
      (three observed) was found for workers with the highest cumulative exposure to
      both dusts. Internal analysis, after adjustment for asbestos exposure, yielded
      rate ratios for categories of exposure to crystalline silica: 1.00 (reference),
      1.37, 1.80, and 1.79. CONCLUSIONS: Asbestos exposure was not an important
      confounder of the association between crystalline silica and mortality from lung
      cancer in this cohort. Although based on a small number of deaths from lung
      cancer, the data suggest possible synergy between these exposures. An extended
      follow up of this cohort is in progress and should enable better assessments of
      independent and combined effects on risk of lung cancer.

PMID- 8882124
TI  - Epidemiology of peripheral joint osteoarthritis.

PMID- 8882126
TI  - Chronic flexor tenosynovitis: missed diagnosis for a decade.

PMID- 8882125
TI  - Management strategies for chronic pain.

PMID- 8882127
TI  - Back pain in the older patient.

PMID- 8882128
TI  - Increased capillary permeability in systemic sclerosis: help or hindrance?

PMID- 8882129
TI  - Incidence of rheumatoid arthritis in Finland during 1980-1990.
AB  - OBJECTIVE: To obtain information on the incidence of rheumatoid arthritis and on
      its recent trends in Finland. METHODS: The study covered those subjects entitled
      to receive specially reimbursed medication for rheumatoid arthritis under the
      nationwide sickness insurance scheme in five out of 21 central hospital districts
      in Finland (population basis about one million adults) during three years: 1980,
      1985, and 1990. RESULTS: The annual incidence of rheumatoid arthritis in 1980 and
      1985, satisfying the American Rheumatism Association 1987 classification
      criteria, was 39/100,000 of the population > or = 16 years of age. The combined
      incidence of rheumatoid factor (RF) positive arthritis and RF negative
      polyarthritis was 46/100,000. A decline of approximately 40% occurred in the
      number of RF negative rheumatoid arthritis cases in 1990 compared with the
      earlier years. The declining trend was statistically significant (P = 0.008).
      CONCLUSION: The decline in incidence of RF negative rheumatoid arthritis in
      Finland may reflect changes in the environment specifically affecting the risk of
      RF negative disease.

PMID- 8882130
TI  - Parasympathetic dysfunction in rheumatoid arthritis patients with ocular dryness.
AB  - OBJECTIVE: To determine whether abnormalities in the function of the autonomic
      nervous system are associated with oral and ocular dryness in rheumatoid
      arthritis. METHODS: Pupillography was done using an infrared light reflection
      method (IRIS) to measure both parasympathetic function (constriction latency and
      the latency of maximum constriction velocity (MCV)) and sympathetic function
      (dilatation latency) in rheumatoid arthritis patients with and without ocular
      dryness. The Schirmer and Saxon tests were used to measure the tear and saliva
      production respectively. RESULTS: The Schirmer and Saxon test results in
      rheumatoid arthritis patients with ocular dryness were reduced (P < 0.05)
      compared with rheumatoid arthritis patients without ocular dryness and healthy
      controls. Constriction latency and MCV latency were prolonged in rheumatoid
      arthritis patients with ocular dryness compared to the other two groups (P <
      0.05). A negative correlation was found between the degree of ocular dryness and
      both constriction latency and MCV latency. No correlation was found between the
      results of pupillography and saliva production. CONCLUSIONS: Parasympathetic
      dysfunction may play a role in ocular dryness in patients with rheumatoid
      arthritis.

PMID- 8882131
TI  - Antibody deficiency associated with gold treatment: natural history and
      management in 22 patients.
AB  - OBJECTIVE: To perform a clinical and immunological study of patients with
      rheumatoid arthritis who develop subnormal serum immunoglobulins on gold
      treatment; to clarify the nature of the defect in antibody production and
      determine the natural history of this adverse reaction; to use this information
      to suggest guidelines for the detection, investigation, and management of this
      complication. METHODS: 22 patients who developed subnormal levels of one or more
      immunoglobulin isotypes while receiving gold treatment were recruited over a 10
      year period from the practice of a single rheumatologist. Antibody production was
      assessed by measurement of total immunoglobulins and of specific antibody
      production against polysaccharide and protein antigens, with test immunisation if
      necessary. RESULTS: Two broad patterns of antibody deficiency were identified:
      (1) (n = 11) mild, affecting only one immunoglobulin isotype and with normal
      specific antibody production. These patients were in general able to continue
      gold without further deterioration in antibody production. (2) (n = 11) severe,
      affecting two or three immunoglobulin isotypes, with defective specific antibody
      production. Six patients developed significant infections and were treated with
      immunoglobulin. Gold was discontinued in all. Normal antibody production
      recovered in nine patients, and in all but one followed for more than one year.
      No relation was seen between duration/dose of gold and antibody deficiency.
      CONCLUSIONS: Gold-induced antibody deficiency may be more common than usually
      recognised. A spectrum of deficiency exists, with some patients developing
      infective complications. Antibody production should be monitored in patients on
      gold treatment.

PMID- 8882132
TI  - Increased concentrations of bone sialoprotein in joint fluid after knee injury.
AB  - OBJECTIVE: To detect evidence for localised changes in bone matrix metabolism
      after joint trauma and in post-traumatic osteoarthritis by quantification of bone
      sialoprotein in joint fluid and serum after knee injury in a cross sectional
      study. METHODS: Samples of knee joint fluid and serum were obtained from
      volunteers with normal knees (n = 19), patients with rupture of the anterior
      cruciate ligament isolated or combined with tear of a meniscus (n = 114), and
      patients with isolated meniscus lesions (n = 80). Concentrations of bone
      sialoprotein were determined by ELISA. Concentrations of other markers of joint
      tissue metabolism in these samples were determined in previous investigations.
      RESULTS: The median concentrations of bone sialoprotein in joint fluid from
      healthy volunteers was 122 ng ml-1 (range 41 to 183). Concentrations of bone
      sialoprotein were increased in both injury groups compared with the reference
      group (median for cruciate ligament injury 146 ng ml-1, range 72 to 339; median
      for meniscus injury 166 ng ml-1, range 75 to 376). After injury, bone
      sialoprotein increased quickly and remained increased for six months. Bone
      sialoprotein in joint fluid was increased only in samples from joints with normal
      or nearly normal (fibrillated) cartilage, and was within reference range in
      joints with radiographic signs of osteoarthritis. Bone sialoprotein
      concentrations in joints with cruciate ligament injury were positively correlated
      with levels of aggrecan and cartilage oligomeric matrix protein fragments, and
      with levels of stromelysin-1 and tissue inhibitor of metalloproteinase-1. The
      ratios between the concentrations of bone sialoprotein in joint fluid and serum
      were > 1 in the majority of the cruciate ligament injury cases. CONCLUSIONS: The
      release of significant amounts of bone sialoprotein into joint fluid in
      connection with acute joint trauma may be associated with injury to, and active
      remodelling of, the cartilage-bone interface and subchondral bone. The findings
      are consistent with dramatic shifts in cartilage, bone, and synovial metabolism
      following joint injury. Bone sialoprotein concentrations in synovial fluid may be
      a useful marker of subchondral injury and remodelling following joint injury.

PMID- 8882133
TI  - Restrictions of T cell receptor beta chain repertoire in the peripheral blood of
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate whether oligoclonal T cell populations occur in
      peripheral blood lymphocytes from patients with systemic lupus erythematosus
      (SLE). METHODS: RNA was extracted from the lymphocytes isolated from whole
      peripheral blood of five female patients fulfilling ARA criteria for SLE and two
      healthy female controls, and synthesised into cDNA. CDR3 length spectratyping was
      performed using a polymerase chain reaction (PCR) run to saturation followed by a
      primer extension with a radioactively labelled primer. The resulting samples, one
      for each of the 23 V beta families, were then run on a polyacrylamide sequencing
      gel to examine the T cell receptor beta chain repertoire at the level of VDJ
      length heterogeneity. RESULTS: The two healthy female controls showed faint
      oligoclonal bands in only two and three V beta families respectively. Three of
      the patients showed a similar degree of oligoclonality to the controls, while the
      other two, who had active disease as shown by SLAM scores of 17 and 19 and in one
      case low C4 and raised C3dg levels, showed marked oligoclonality of their T cell
      beta chain repertoire affecting more than 17 of the 23 V beta families analysed.
      CONCLUSIONS: Using the technique of CDR3 length spectratyping, restriction of T
      cell receptor beta chain usage by peripheral blood T cells in patients with SLE
      has been demonstrated for the first time.

PMID- 8882134
TI  - Cytokine production by endothelial cells infected with human T cell lymphotropic
      virus type I.
AB  - OBJECTIVE: To investigate the ability of human T cell lymphotropic virus type I
      (HTLV-I) to infect endothelial cells and induce cytokine production by these
      cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were cocultured
      with HTLV-I infected T cell line (MT-2 cells) or uninfected T cell line (CEM
      cells). RESULTS: Following coculture with MT-2 cells, endothelial cells expressed
      HTLV-I specific core antigens. Endothelial cells cocultured with MT-2 cells
      produced significant amounts of several cytokines, including interleukin (IL)-1
      alpha, IL-6, granulocyte colony stimulating factor (G-CSF), and
      granulocyte/macrophage colony stimulating factor (GM-CSF), compared with
      endothelial cells cocultured with CEM cells. Coculturing of endothelial cells
      with MT-2 and CEM cells failed to produce detectable amounts of IL-1 beta and
      tumour necrosis factor alpha (TNF-alpha). The production of cytokines by
      endothelial cells cocultured with MT-2 cells was more persistent than that by
      endothelial cells cocultured with CEM cells after several passages. Furthermore,
      the production was blocked by cocultivation of endothelial cells and MT-2 cells
      using the Millicell system. Finally, after cocultivation of endothelial cells and
      MT-2 cells, endothelial cells positive for HTLV-I antigen were stained by anti-GM
      CSF antibody. CONCLUSIONS: HTLV-I can infect endothelial cells, resulting in
      their active production of several cytokines, such as IL-1 alpha, IL-6, G-CSF,
      and GM-CSF. These findings strongly suggest that the excess production of these
      cytokines by HTLV-I infected endothelial cells may be involved in the
      pathogenesis of HTLV-I associated inflammatory diseases.

PMID- 8882135
TI  - Transplantation with allogenic bone marrow from a donor with systemic lupus
      erythematosus (SLE): successful outcome in the recipient and induction of an SLE
      flare in the donor.
AB  - OBJECTIVE: To investigate the transfer of autoimmunity by allogenic bone marrow
      transplantation. METHODS: Bone marrow transplantation was performed in a 43 years
      old man with acute myeloid leukaemia (AML) in remission. The donor was his HLA
      identical brother who had a mild systemic lupus erythematosus (SLE).
      Autoantibodies, including antinuclear, anti-C1q, and anticardiolipin antibodies,
      were measured before and after transplantation. RESULTS: Transient mild graft
      versus host disease (GvHD) developed in the recipient in the weeks following
      transplantation. The donor had persistently high concentrations of anti-C1q
      antibodies to the collagenous region of the complement component C1q. Three
      months after transplantation the recipient developed antiC1q antibodies that
      persisted for two months. No other autoantibodies and no SLE-like manifestations
      appeared. Chronic GVHD started five months posttransplant and responded to
      intensified immunosuppressive treatment. Three years post-transplant the patient
      was in unmaintained remission. Within a few weeks after bone marrow donation the
      donor's disease was exacerbated with development of severe pulmonary alveolitis
      which required treatment with cyclophosphamide. CONCLUSIONS: When bone marrow
      transplantation was performed in a patient with AML with bone marrow from an HLA
      identical brother who had SLE, no evidence of transfer of disease was obtained.
      However, the recipient temporarily produced anti-C1q antibodies which was a
      characteristic feature of the donor's SLE and was probably produced by the
      transplant. The flare of the donor's SLE might be related to the bone marrow tap.

PMID- 8882136
TI  - Value of synovial fluid interleukin-1 beta determination in predicting the
      outcome of psoriatic monoarthritis.
AB  - OBJECTIVE: To investigate the value of synovial fluid analysis in predicting the
      outcome of psoriatic monoarthritis. METHODS: In synovial fluid from knee joints
      of 18 patients with psoriatic monoarthritis lasting less than six months, white
      blood cell count, acid phosphatase, lysozyme, and interleukin (IL)-1 beta were
      determined. ESR and serum C reactive protein were also measured. To define the
      outcome, the patients were monitored for at least three years and then subdivided
      into those with polyarthritis and those without. RESULTS: Among the blood and
      synovial fluid indices considered, synovial fluid IL-1 beta was the only variable
      which differed between the patients who developed polyarthritis, within three
      years and those without polyarthritis after this time, at 20.82(SD 8.79) v
      4.19(4.73) pg ml-1, P < 0.0001). A correlation was found between synovial fluid
      IL-1 beta concentrations and the number of affected joints after three years (r =
      0.739, P < 0.0001). CONCLUSIONS: Determination of synovial fluid IL-1 beta at
      disease onset may be useful in revealing the outcome of psoriatic monoarthritis
      since, among the variables considered in our study, this was the only one capable
      of predicting the evolution of monoarticular psoriatic arthritis to
      polyarthritis.

PMID- 8882137
TI  - Grouped caging predisposes male mice to ankylosing enthesopathy.
AB  - OBJECTIVE: To evaluate the number of males per cage as a possible risk factor for
      murine ankylosing enthesopathy (ANKENT)--a spontaneous joint disease with
      parallels to human seronegative spondylarthropathies--since ANKENT shows
      incomplete penetrance of genetic susceptibility factors among individuals living
      in a stable environment. METHODS: Frequency of ANKENT was compared among males
      housed with females, with other males, or alone. RESULTS: In three independent
      cohorts, a trend was observed that males housed with females rarely develop the
      disease, in contrast to males housed with other males (P < 0.25, P < 0.05, and P
      < 0.01). Furthermore, no males caged alone developed ANKENT, whereas disease did
      occur in males grouped together (P < 0.01). When healthy males (retired breeders)
      were recaged either alone or with other males, ANKENT developed among the grouped
      males only (P < 0.005). CONCLUSIONS: Caging males together is a relative risk
      factor for ANKENT. Grouped caging may perturb the immune system through endocrine
      pathways or modify microbiological load through behaviour (for example, infection
      due to biting).

PMID- 8882138
TI  - Behcet disease: advantageous against development of neoplasia?

PMID- 8882139
TI  - Parvovirus B19 and acute joint swelling in rheumatoid arthritis patients.

PMID- 8882140
TI  - Down syndrome with coexistent gout: report of six patients and possible reasons
      for the scarcity of descriptions of this association.

PMID- 8882141
TI  - Definition of hip osteoarthritis for epidemiological studies.

PMID- 8882142
TI  - Definitions of osteoarthritis in the knee and hand.

PMID- 8882143
TI  - Occurrence of osteoarthritis of the peripheral joints in European populations.

PMID- 8882144
TI  - The occurrence of osteoarthritis outside Europe.

PMID- 8882145
TI  - Genetics of osteoarthritis.
AB  - The available evidence suggests that genetic factors have a major role in
      osteoarthritis. It has been believed for over 50 years that a strong genetic
      component to certain forms of osteoarthritis is present. This genetic influence
      has now been estimated to be up to 65% in a recent twin study. The nature of the
      genetic influence in osteoarthritis is speculative and may involve either a
      structural defect (that is, collagen), alterations in cartilage or bone
      metabolism, or alternatively a genetic influence on a known risk factor for
      osteoarthritis such as obesity. Exciting work has showed that mutations in the
      collagen type 2 are important in some rare, familial forms of osteoarthritis.
      Further work is needed on isolating the gene or genes involved in the
      pathogenesis of this common, disabling condition.

PMID- 8882146
TI  - Does excess weight cause osteoarthritis and, if so, why?

PMID- 8882147
TI  - Obstetric and gynaecological factors in susceptibility to peripheral joint
      osteoarthritis.
AB  - There is clear evidence that the age period coinciding with the peak age of the
      menopause is associated with an increased prevalence of osteoarthritis and this
      fits in with clinical observation of high likelihood of presentation at this age.
      A number of pieces of biological evidence also support the notion that changes in
      sex hormone status might influence risk of degenerative disease at peripheral
      joint sites. There do not appear, however, to be any important epidemiological
      predictors based on menstrual or obstetric history that might be useful in
      predicting who these women might be.

PMID- 8882148
TI  - Sex hormones and the risk of osteoarthritis in women: epidemiological evidence.

PMID- 8882149
TI  - Osteoarthrosis of the knee and physical load from occupation.

PMID- 8882150
TI  - Occupational activity and the risk of hip osteoarthritis.

PMID- 8882151
TI  - Physical activity at leisure and risk of osteoarthritis.
AB  - A summary of the evidence linking exercise and osteoarthritis is given in the
      table. In summary, normal joints appear to tolerate prolonged vigorous low impact
      exercise without accelerated development of osteoarthritis. The risk of
      developing osteoarthritis appears to be increased in sporting activities that
      continually expose normal joints to high levels of impact or torsional loading
      and in individuals who continue sporting activities after they have injured
      supporting structures in the joint (like ligaments, tendons, and menisci). The
      hypothesis that high impact loads to joints over time will accelerate the
      development of osteoarthritis in exposed joints must now be examined in a
      longitudinal study.

PMID- 8882152
TI  - Prognosis of osteoarthritis.

PMID- 8882153
TI  - Some new twists in the regulation of gene expression by thyroid hormone and
      retinoic acid receptors.
AB  - Recent studies indicate that heterodimeric nuclear receptors utilize several
      novel mechanisms for increasing the complexity of transcriptional responses to
      hormonal stimuli. By binding as heterodimers, these receptors can potentially
      respond to more than one activating ligand. Allosteric interactions between the
      ligand binding domains of RXR and its heterodimeric partners regulate the binding
      of RXR ligands, resulting in either selective or dual transcriptional responses.
      Regulation of the relative levels of expression of different heterodimeric
      partners that permit signaling through RXR is likely further to expand the
      patterns of transcriptional responses that can occur through a given response
      element. Heterodimeric nuclear receptors also bind to asymmetric response
      elements with specific polarities that result from the formation of cooperative
      interfaces between DNA binding domains. The DNA binding interface serves to
      determine the response element specificity of different heterodimers based on the
      spacing between half sites. The specific polarity of DNA binding has also been
      shown to provide a mechanism for regulating the transcriptional responses of
      retinoic acid receptors to activating ligands through the differential control of
      co-repressor interactions. The identification and characterization of co
      activator and co-repressor molecules is likely to provide a very interesting next
      chapter to the mechanisms of steroid hormone action.

PMID- 8882154
TI  - Parathyroid hormone-related protein (PTHrP) action in rat articular chondrocytes:
      comparison of PTH(1-34), PTHrP(1-34), PTHrP(1-141), PTHrP(100-114) and antisense
      oligonucleotides against PTHrP.
AB  - Parathyroid hormone-related protein (PTHrP) is thought to be an important
      autocrine/paracrine factor for chondrocyte metabolism since mice lacking the
      PTHrP gene exhibit abnormal cartilage development. To determine the biological
      role of PTHrP in chondrocytes, we first compared the agonist potency of human (h)
      PTHrP(1-34) with hPTH(1-34) in cultured rat articular chondrocytes. Neither
      hPTHrP(1-34) nor hPTH(1-34) altered basal DNA synthesis, but attenuated the
      stimulatory effect of transforming growth factor beta (TGF-beta). Both agents
      suppressed the expression of alpha(1) type II collagen mRNA in a dose-response
      fashion with the same potency. In addition, the action of exogenously added
      hPTHrP(1-34) and hPTH(1-34) on intracellular cAMP and [Ca2+]i levels was similar.
      We next compared the effect of PTHrP within its entire amino acid sequence (1
      141). With regard to thymidine incorporation, alpha(1) type II collagen gene
      expression and accumulation of cAMP and [Ca2+]i level, there was no significant
      difference between hPTHrP(1-34) and hPTHrP(1-141). PTHrP C-terminal (100-114) did
      not show any function. To further investigate PTHrP function, intracellular PTHrP
      translation was inhibited by a transgene of antisense oligonucleotides against
      PTHrP. Antisense oligonucleotides decreased PTHrP mRNA translation, specifically
      inhibited DNA synthesis in control as well as TGF-beta-treated chondrocytes and
      enhanced alpha(1) type II collagen mRNA expression in TGF-beta-treated
      chondrocytes. These results suggest that there is no significant difference
      between exogenously added hPTH(1-34), hPTHrP(1-34) and PTHrP(1-141) with regard
      to the biological action of these agents, including cell growth, differentiation
      and second messenger pathway. However, the result of DNA synthesis in the
      antisense PTHrP-inhibition study suggests that intracellular PTHrP may have an as
      yet unknown biological role, in addition to a classical PTH/PTHrP receptor
      mediated function in the rat articular chondrocyte.

PMID- 8882155
TI  - Acute inhibitory effect of excess iodide on ornithine decarboxylase in the
      thyroid of propylthiouracil-treated rats.
AB  - Polyamines such as putrescine, spermidine and spermine have been thought to play
      an important role in thyroid growth induced by goitrogens. Reduced biosynthesis
      of these polyamines might play a role in the antigoitrogenic effects of excess
      iodide. This study was designed to examine the effect of potassium iodide (KI) on
      ornithine decarboxylase (ODC), a rate-limiting enzyme in the biosynthesis of
      polyamines. Thyroidal ODC activity, protein content and mRNA were increased in
      rats made hypothyroid by 10 days of propylthiouracil treatment. The increase in
      ODC activity was suppressed after subcutaneous injection of KI (13mg/kg body
      weight); the apparent half-life of ODC activity after the treatment was estimated
      to be 19 min and the maximum suppression (90%) was seen 60 min after the
      treatment. On the other hand, administration of iodine-containing compounds
      including L-thyroxine, L-di-iodotyrosine,amiodarone, iopanoic acid and
      erythrosine showed no significant effect on ODC activity. The inhibitory effect
      of excess iodide was not reversed by pretreatment with dibutyryl cAMP and
      theophylline. The amount of immunoreactive ODC protein was reduced by iodide
      treatment (40%). However, the decrease was not as great as the decrease in ODC
      activity (90%). No significant change in thyroidal ODC mRNA content was seen 1
      and 3 h following KI treatment. These results suggest that excess iodide reduces
      ODC activity in the rat thyroid gland by a post-transcriptional mechanism.

PMID- 8882156
TI  - Disrupted co-ordination of Pax-8 and thyroid transcription factor-1 gene
      expression in a dedifferentiated rat thyroid tumour cell line derived from FRTL
      5.
AB  - The mutant rat thyroid cell line FRTL-5/TA, isolated from a non-functional tumour
      which originated spontaneously from wild-type FRTL-5 cells, shows autonomous TSH
      independent growth and loss of the thyroid-specific phenotype, lacking thyroid
      specific expression of thyroglobulin (Tg) and thyroid peroxidase (TPO) genes. To
      investigate the role of the transcription factors Pax-8 and thyroid transcription
      factor-1 (TTF-1) in rat thyroid tumorigenesis, RNA expression of these two
      thyroid-specific nuclear factors was measured in FRTL-5/TA tumour cells and
      compared with the expression in wild-type FRTL-5 cells. TTF-1 gene expression was
      similar to that in wild-type FRTL-5, and showed a similar down-regulation after
      stimulation with TSH. The finding suggested normal TTF-1 mRNA and protein
      expression in both cell lines. By contrast, Pax-8 mRNA transcript signal was
      markedly reduced in FRTL-5/TA cells, reaching levels as low as 8% of the normal,
      basal level in FRTL-5 cells. These data indicated that the loss of thyroid
      specific expression of Tg and TPO genes in FRTL-5/TA cells was not related to
      changes in TTF-1 gene expression but rather to reduced Pax-8 gene expression. It
      was concluded that a disruption of the co-ordinated expression of TTF-1 and Pax-8
      is implicated in the loss of thyroid phenotype of FRTL-5/TA cells in terms of
      reduced Tg and TPO expression.

PMID- 8882157
TI  - Comparison between urinary pyridinium cross-links and hydroxylysine glycosides in
      monitoring the effects of ovariectomy and 17 beta-estradiol replacement in aged
      rats.
AB  - This study was undertaken to assess the sensitivity of hydroxylysylpyridinoline
      (HP), lysylpyridinoline (LP), galactosylhydroxylysine (GHyl) and
      glucosylgalactosylhydroxylysine (GGHyl) to monitor bone response to estrogen
      deficiency and replacement by comparing their excretory patterns in
      ovariectomized aged (11-14 months old) rats. The ovariectomized (OVX) rats were
      randomized into two groups: (1) OVX plus vehicle; (2) OVX plus 17 beta-estradiol
      (17-beta E, 10 micrograms/kg, s.c., 4 days/week). Treatment with 17-beta E
      started immediately after OVX and continued for 60 days. The collagen catabolites
      were measured in urine for 1 month before OVX and thereafter for 60 days. In
      temporal coincidence with urine collection, bone area and bone mineral density
      (BMD) of lumbar vertebrae, femoral diaphysis and distal metaphysis were measured
      by dual-energy X-ray absorptiometry. In the untreated rats, BMD of the femoral
      metaphysis and lumbar vertebrae decreased significantly and the urinary excretion
      of LP, HP, GHyl and GGHyl increased with different patterns. In the treated rats,
      17-beta E replacement prevented the increment in LP excretion, partially
      prevented the increase in HP excretion, but had no effect on the excretion of
      GHyl and GGHyl. In conclusion pyridinolines and glycosides have different
      sensitivities to the bone response to OVX. Glycoside excretion after OVX also
      reflects metabolic processes not strictly related to bone loss and, in contrast
      with LP, is not sensitive to estrogen replacement.

PMID- 8882158
TI  - Ontogeny of growth hormone, insulin-like growth factor-I, estradiol and cortisol
      in the growing lamb: effect of testosterone.
AB  - Exogenous sex steroids have altered growth hormone secretion in some domestic
      species. This study examined whether different physiological concentrations of
      testosterone alter muscle growth in sheep through modification of the
      somatotropic axis. The effects of testosterone on growth hormone (GH), insulin
      like growth factor-I (IGF-I), estradiol (E2) and cortisol concentrations in
      growing lambs were evaluated in 20 rams, 20 wethers and 20 wethers receiving
      subcutaneous testosterone replacement therapy. Two animals from each of the three
      testosterone status groups were slaughtered at 14-day intervals from 49 to 133
      days of age, and then at 28-day intervals until 217 days of age for a total of 10
      slaughter ages. Animals were sampled every 10 min for an 8-h period 1 day prior
      to slaughter to characterize the episodic patterns of GH and testosterone.
      Immediately after slaughter, the semitendinosus, splenius and triceps brachii
      muscles were removed, trimmed of adhering fat and connective tissue, and weighed.
      Testosterone increased the combined muscle weight. GH concentrations decreased
      during the course of the experiment. However, there was no effect of testosterone
      on GH mean, baseline, amplitude or GH pulse frequency measured by PULSAR. IGF-I
      concentrations increased in response to testosterone treatment. Testosterone had
      no effect on cortisol levels while E2 levels were increased after 133 days.
      Increased muscle growth due to testosterone appeared to be caused either by a
      direct effect or by increased levels of IGF-I independent of circulating GH
      concentrations.

PMID- 8882159
TI  - Lectin-binding assays for the isoforms of human erythropoietin: comparison of
      urinary and four recombinant erythropoietins.
AB  - Assays have been developed for the isoforms of erythropoietin (EPO) based on
      their binding to eight different lectins. These assays were used to compare the
      isoform compositions of two preparations of human urinary EPO (uEPO) and four
      preparations of recombinant DNA-derived human EPO (rEPO), which had been shown to
      differ in their biological and immunological properties and in their isoform
      composition as judged by isoelectric focusing and electrophoresis. Agarose-bound
      Ricinus communis agglutinin I (RCA), Erythrina cristagalli agglutinin (ECA),
      Maackia amurensis leukoagglutinin (MAL), Sambucus nigra agglutinin (SNA),
      Lycopersicon esculentum agglutinin (LEA), concanavalin A (Con A), Phaseolus
      vulgaris agglutinin-L4 (L-PHA) and Agaricus bisporus agglutinin (ABA) were used
      to bind EPO isoforms possessing: N-glycans containing non-sialylated outer Gal
      beta 1-4GlcNAc (RCA and ECA), NeuAc alpha 2-3Gal beta 1-4GlcNAc (MAL), NeuAc
      alpha 2-6Gal (SNA), or repeating Gal beta 1-4GlcNAc sequences (LEA); biantennary
      N-glycans (Con A); tetraantennary and 2,6-branched triantennary N-glycans (L
      PHA); and O-glycans containing NeuAc alpha 2-6GalNAc (SNA) and Gal beta 1-3GalNAc
      (ABA). Free EPO was measured by mouse spleen cell bioassay or immunoassay.
      Estimates from most lectin-binding assays were reproducible between assays and
      batches of lectin-agarose, although batches of MAL- and ABA-agarose, and to a
      lesser extent LEA-agarose, differed in their EPO-binding. Lectin-binding assays
      showed differences between the isoform compositions of all EPOs, including the
      two Chinese hamster ovary cell-derived rEPOs, with RCA- and ECA-binding assays
      being the most discriminating. Lectin-binding estimates provided evidence that
      uEPO differs from these rEPOs in its lower content of isoforms with biantennary N
      glycans and higher content of those with multiantennary N-glycans, and in its
      lower content of isoforms with N-glycans possessing repeating Gal beta 1-4GlcNAc
      sequences and of those with O-glycans containing Gal beta 1-3GalNAc. Lectin
      binding estimates also indicated that, contrary to some reports, uEPO possesses
      Gal beta 1-3GalNAc-containing O-glycans but not NeuAc alpha 2-6GalNAc-containing
      O-glycans or NeuAc alpha 2-6Gal-containing N-glycans. Most groups of lectin-bound
      EPO isoforms did not differ in their relative bioactivities and
      immunoreactivities. However, estimates for ABA-bound EPO isoforms suggested that
      O-glycans might influence the bioactivity of EPO differently to its
      immunoreactivity. Furthermore, the bioactivities of some ECA-bound EPO isoforms
      were higher, and those of some of the MAL-bound EPO isoforms lower, than their
      immunoreactivities, consistent with the reported enhancement of EPO in vitro
      bioactivity by desialylation.

PMID- 8882160
TI  - The effects of steroidal and non-steroidal ovarian hormones on pituitary
      responsiveness to gonadotrophin surge-attenuating factor.
AB  - Primary pituitary cultures from adult female rats were used to investigate the
      effects of steroidal (oestradiol and progesterone) and non-steroidal (inhibin,
      follistatin) ovarian hormones on the suppressive actions of the ovarian factor
      gonadotrophin surge-attenuating factor (GnSAF) in the control of gonadotrophin
      secretion. The source of GnSAF was a chromatographic preparation from follicular
      fluid containing four distinct protein bands as resolved on SDS-PAGE. Oestradiol
      and progesterone added alone had no effect on gonadotrophin secretion but had a
      wide range of effects on the suppression of both LH and FSH secretion caused by
      the non-steroidal factors. Oestradiol, progesterone and oestradiol+progesterone
      enhanced the suppressive actions of GnSAF on GnRH-induced LH secretion (causing
      19.3 +/- 5.2% (P < 0.05), 41.9 +/- 3.4% (P < 0.001) and 32.2 +/- 5.3% (P < 0.001)
      greater suppression than GnSAF alone). Progesterone and oestradiol+progesterone
      completely abolished the suppression of basal FSH secretion caused by inhibin
      (causing 157.1 +/- 22.2%, P < 0.001, and 160.9 +/- 11.3%, P < 0.001, stimulation
      compared with inhibin alone). Separately the steroids had no effect on the
      suppression of gonadotrophin secretion caused by follistatin. However, in
      combination, oestradiol+progesterone potentiated the suppressive actions of
      follistatin on GnRH-induced LH secretion causing 29.9 +/- 5.3% (P < 0.05) greater
      suppression than follistatin alone. In combination, high-dose follistatin and
      GnSAF caused 31.1 +/- 6.5% (P < 0.01) greater suppression than GnSAF alone. Thus
      in combination high-dose follistatin and GnSAF have additive effects on the
      suppression of GnRH-induced LH secretion. Recombinant human inhibin and GnSAF
      added in combination had little further effect compared with either alone
      suggesting that they may have a similar mechanism of action at the pituitary
      level. These results demonstrate that while FSH secretion in vitro is mainly
      controlled by inhibin and follistatin, LH secretion is affected by the presence
      of a whole range of factors. We have demonstrated that oestradiol and
      progesterone potentiate the suppressive actions of GnSAF in vitro. These data are
      compatible with the suggestion that in the late follicular phase it is falling
      levels of GnSAF that allow positive feedback of the steroids on the pituitary to
      elicit the LH surge, rather than increases in the stimulatory effects of the
      ovarian steroids overcoming GnSAF. The actions of GnSAF on the pituitary may be
      modulated by follistatin but it is unlikely that inhibin has any modulatory
      effects on the GnSAF-induced suppression of LH secretion.

PMID- 8882161
TI  - Luteolytic effect of LH: inhibition of 3 beta-hydroxysteroid dehydrogenase and
      stimulation of 20 alpha-hydroxysteroid dehydrogenase luteal activities in late
      pregnant rats.
AB  - The mechanisms associated with the onset of luteolysis in the pregnant rat are
      not well known. The effect of a specific rat LH antiserum (AS-rLH) and of ovine
      LH (oLH) on luteal steroidogenesis on day 19 of pregnancy was examined. Rat LH
      antiserum administered intrabursally at 1000-1100 h on day 19 of pregnancy
      prevented the physiological decrease in 3 beta-hydroxysteroid dehydrogenase (3
      beta-HSD) activity, the increase in 20 alpha-hydroxysteroid dehydrogenase (20
      alpha-HSD) activity and the fall in serum progesterone (P4) level observed at
      1800 h on day 21 of pregnancy. To see if oLH has a direct effect on luteal
      steroidogenesis, the gonadotrophin was injected into the periovarian bursa. The
      intrabursa treatment with 1 microgram oLH on day 19 of pregnancy at 0800-0900 h
      did not modify corpus luteal function 36 h after treatment, but treatment with 4
      micrograms oLH per ovary induced a significant progressive decrease in luteal 3
      beta-HSD activity starting 12 h after treatment, while a significant increase in
      20 alpha-HSD activity, concomitant with a decrease in serum P4 level, occurred 48
      h after treatment. Luteal P4 content decreased with respect to control groups 36
      and 48 h after intrabursal treatment with 4 micrograms oLH. The intrabursal
      administration of 8 micrograms oLH induced an increase in 20 alpha-HSD activity
      and a decrease in 3 beta-HSD activity 36 h after treatment. Administration of 4
      micrograms oLH per ovary on day 8 of pregnancy induced a significant increase in
      serum P4 levels without modifying 3 beta-HSD activity. In rats treated with oLH
      on day 19 of pregnancy the decrease in 3 beta-HSD activity occurred 36 h before
      the significant increase in 20 alpha-HSD activity and serum P4 level. In
      conclusion, the luteal enzymatic activity changes and the significant decrease in
      the intraluteal P4 concentration induced by the intrabursal administration of oLH
      and the clear effect of AS-rLH preventing the physiological luteal changes
      preceding parturition provide good evidence of an intraovarian action of LH
      during the normal progression of luteolysis in late pregnant rats.

PMID- 8882162
TI  - Immunization of male rabbits with sheep luteal receptor to LH results in
      production of antibodies exhibiting hormone-agonistic and -antagonistic
      activities.
AB  - Antibodies to LH/chorionic gonadotrophin receptor (LH/CG-R; molecular weight 67
      000), isolated in a homogenous state (established by SDS-PAGE and ligand
      blotting) from sheep luteal membrane using human CG (hCG)-Sepharose affinity
      chromatography, were raised in three adult male rabbits (R-I, R-II and R-III).
      Each of the rabbits received 20-30 micrograms of the purified receptor in
      Freund's complete adjuvant at a time. Primary immunization was followed by
      booster injection at intervals. Production of receptor antibodies was monitored
      by (1) determining the dilution of the serum (IgG fraction) that could
      specifically bind 50% of 125I-LH/CG-R added and (2) analysing sera for any change
      in testosterone levels. Following primary immunization and the first booster, all
      three rabbits exhibited a 2.5- to 6.0-fold increase in serum testosterone over
      basal levels and this effect was spread over a period of time (approximately 40
      days) coinciding with the rise and fall of receptor antibodies. The maximal
      antibody titre (ED50) produced at this time ranged from 1:350 to 1:100 to below
      detectable limits for R-I, R-II and R-III respectively. Subsequent immunizations
      followed by the second booster resulted in a substantial increase in antibody
      titre (ED50 of 1:5000) in R-I, but this was not accompanied by any change in
      serum testosterone over preimmune levels, suggesting that with the progress of
      immunization the character of the antibody produced had also changed. Two pools
      of antisera from R-I collected 10 days following the booster (at day 70 (bleed I)
      and day 290 (bleed II)) were used in further experiments. IgG isolated from bleed
      I but not from bleed II antiserum showed a dose-dependent stimulation of
      testosterone production by mouse Leydig cells in vitro, thus confirming the in
      vivo hormone-mimicking activity of antibodies generated during the early
      immunization phase. The IgG fractions from both bleeds were, however, capable of
      inhibiting (1) 125I-hCG binding to crude sheep luteal membrane (EC50 of 1:70 and
      1:350 for bleed I and II antisera respectively) and (2) ovine LH-stimulated
      testosterone production by mouse Leydig cells in vitro, indicating the presence
      of antagonistic antibodies irrespective of the period of time during which the
      rabbits were immunized. The fact that bleed I-stimulated testosterone production
      could be inhibited in a dose-dependent manner by the addition of IgG from bleed
      II to the mouse Leydig cell in vitro assay system showed that the agonistic
      activity is intrinsic to the bleed I antibody. The receptor antibody (bleed II)
      was also capable of blocking LH action in vivo, as rabbits passively (for 24 h
      with LH/CG-R antiserum) as well as actively (for 430 days) immunized against
      LH/CG-R failed to respond to a bolus injection of LH (50 micrograms). At no time,
      however, was the serum testosterone reduced below the basal level. This study
      clearly shows that, unlike with LH antibody, attempts to achieve an LH deficiency
      effect in vivo by resorting to immunization with holo LH receptor is difficult,
      as receptor antibodies exhibit both hormone-mimicking (agonistic) as well as
      hormone-blocking (antagonistic) activities.

PMID- 8882163
TI  - Activation of protein kinase A and protein kinase C mediates the depolarising
      effect of LH in ovine cumulus-corona cells.
AB  - We have studied the changes in membrane potential induced by LH in cumulus and
      granulosa cells isolated from sheep antral follicles. The investigation was
      carried out by using a non-invasive technique based on the use of a membrane
      potential sensitive probe, bis-oxonol. The membrane potential of mural granulosa
      cells was totally unaffected by LH, while that of cumulus or corona cells showed
      a marked depolarisation, starting 2-3 min after the addition of the hormone and
      plateauing after 5-10 min. None of the cells tested reacted to FSH. In the second
      part of the experiment the role of protein kinase A (PKA) and protein kinase C
      (PKC) in mediating the effect of LH was studied. The selective activation of PKA
      or PKC induced in cumulus-corona cells a rapid hyperpolarisation due to increased
      Cl and K conductance respectively. By contrast, the simultaneous activation of
      the two kinases induced a rapid membrane depolarisation due to the progressive
      decrease in K conductance. The activation of each kinase or their combined
      stimulation did not induce any change in the membrane potential of mural
      granulosa cells. These data demonstrated that LH has a depolarising effect
      regionally circumscribed to cumulus-corona cells and that this depolarisation
      depends on a reduction of K conductance caused by the activation of PKA and PKC.

PMID- 8882164
TI  - Potent inhibitory effects of steroids in an in vitro model of angiogenesis.
AB  - The regulation of angiogenesis in the ovarian follicle and corpus luteum is
      unclear. Steroids are produced at very high concentrations in these tissues and
      we therefore examined the effect of steroids on angiogenesis in vitro. Explants
      of rat aorta were embedded in collagen gel and cultured in serum-free medium.
      Capillary-like microvessels were produced from the explants and microvessel
      number and length were measured in the presence and absence of steroids. At a
      concentration of 10 micrograms/ml, cortisol, progesterone, 17 alpha
      hydroxyprogesterone and medroxyprogesterone acetate produced degeneration of
      microvessels after 7 days of steroid treatment (P < 0.01). Androstenedione and
      tetrahydro-S-(11-deoxytetrahydrocortisol) (tetrahydro S) produced degeneration at
      a slower rate: androstenedione inhibited microvessel growth after 11 days (P <
      0.01) and tetrahydro S after 14 days (P < 0.05). Oestriol had no effect on
      microvessels; oestrone had a slow degenerative effect with significant inhibition
      seen after 14 days (P < 0.01). Oestradiol-17 beta at a concentration of 10
      micrograms/ml completely inhibited microvessel growth from the explant cultures
      (P < 0.01) while at 1 microgram/ml it caused degenerative effects on growing
      microvessels. The effects of oestradiol and cortisol were reversible on removal
      of steroid-containing medium and replacement with 10% serum. We conclude that
      oestradiol may modulate angiogenesis in tissues in which the steroid
      concentration is high.

PMID- 8882165
TI  - Growth hormone binds to a single high affinity receptor site on mouse
      osteoblasts: modulation by retinoic acid and cell differentiation.
AB  - Growth hormone (GH) exerts direct differentiative and proliferative effects on
      osteoblasts. We studied 125I-labeled human (h) GH binding to primary mouse
      osteoblasts derived from collagenase-treated 18-day fetal mouse calvaria.
      Scatchard analysis of the data revealed a single class of high affinity GH
      receptors (apparent Ka = 5.74 x 10(9) M-1) with 2200 sites per cell. Affinity
      crosslinking and SDS-PAGE electrophoresis showed two bands with apparent
      molecular masses of 120 and 70 kDa. Mouse osteoblasts express GH receptor mRNA
      with gene transcripts of 4.2 and 1.2 kb, at levels which reach approximately 1/6
      of those in mouse liver and 1/3 of those in mouse muscle. Two populations of
      undifferentiated and diffentiated osteoblasts, obtained by sequential collagenase
      digestion of mouse calvaria, were used to study the relationship between
      osteoblastic phenotype and GH receptor expression. Although the affinity of the
      receptors in undifferentiated and differentiated cells was the same, the capacity
      was significantly higher (1.45 +/- 1.0% vs 2.39 +/- 0.9%, P = 0.03) in
      differentiated cells. This stresses the specific importance of the osteoblast as
      a target cell for GH. The differentiating potential of the vitamin A derivative
      retinoic acid was subsequently used experimentally to induce differentiation in
      the cells. Retinoic acid increased 125I-hGH binding to preosteoblasts (153%, P =
      0.02). Together, these data demonstrate the presence of a high affinity GH
      receptor in mouse osteoblasts which is related to differentiation.

PMID- 8882166
TI  - The effect of oxytocin and oestradiol on the action of conceptus secretory
      protein in progesterone-treated ovariectomized ewes.
AB  - In intact cyclic ewes intrauterine infusion of conceptus secretory proteins
      results in the suppression of both endometrial oxytocin receptor concentrations
      and oxytocin-induced prostaglandin F2 alpha release. However, similar infusion in
      progesterone-treated ovariectomized ewes, while suppressing endometrial oxytocin
      receptors, does not fully inhibit oxytocin-induced prostaglandin F2 alpha
      release. To examine whether this anomaly resulted from an inadequate simulation
      of the luteal phase in the ovariectomized ewe treated with progesterone alone,
      the effects of additional treatment with two other ovarian hormones, oestradiol
      17 beta and oxytocin, was investigated. Rather than permitting conceptus
      secretory protein to successfully inhibit oxytocin-induced prostaglandin F2 alpha
      release, treatment with oestradiol-17 beta in addition to progesterone actually
      resulted in an advancement in the timing of release. However, treatment with
      oxytocin, alone or in combination with oestradiol, permitted the full inhibition
      of oxytocin-induced prostaglandin F2 alpha release. To confirm that this effect
      did not result from the action of oxytocin alone, independently of the action of
      conceptus secretory protein, a second experiment was undertaken using a similar
      protocol but without the infusion of conceptus secretory protein. In this
      situation, oxytocin-induced prostaglandin F2 alpha release was only partially
      inhibited suggesting that both luteal oxytocin and conceptus secretory proteins
      are necessary to facilitate the full inhibition of luteolysis during early
      pregnancy in the ewe.

PMID- 8882167
TI  - Changes in oxytocin receptor mRNA in the rat uterus measured by competitive
      reverse transcription-polymerase chain reaction.
AB  - Large changes in the responsiveness of target organs to oxytocin are thought to
      originate from alteration of the number of oxytocin receptors (OTR). To elucidate
      the molecular mechanisms regulating the synthesis of the OTR, we developed a
      competitive reverse transcription-PCR protocol to measure OTR mRNA. We
      synthesized cRNA comprising a small stuffer introduced into the target mRNA.
      Using this cRNA as an internal standard, we made a quantitative estimation of OTR
      mRNA. Application of this method to the rat uterus revealed that the mean levels
      of OTR mRNA remained unchanged until 1030-1100 h on day 21 of pregnancy,
      increased significantly after 2200-2230 h on the same day and declined rapidly
      after parturition. A similar rapid increase in uterine OTR mRNA content was
      observed in rats given prostaglandin on day 18, inducing premature delivery on
      day 19 of pregnancy. All parturient rats had higher OTR mRNA levels regardless of
      whether parturition was spontaneous or prostaglandin induced. However, in a few
      rats, OTR mRNA remained as low as that observed during mid pregnancy even on day
      22 of gestation, the expected day of parturition in about 70% of the rats in our
      colony. A similar increase in uterine OTR mRNA content to that observed at
      parturition was induced by oestrogen treatment for 3 days in ovariectomized
      virgin rats, but concomitant injection of progesterone did not influence the
      effect of oestrogen. The present results revealed that the large increase of
      uterine OTR at the peripartum period is accompanied by an increase in OTR mRNA
      content that may be brought about, at least in part, by increased oestrogen
      secretion following luteolysis.

PMID- 8882168
TI  - Relaxin stimulates atrial natriuretic peptide secretion in perfused rat heart.
AB  - Relaxin, a reproductive hormone of the insulin-like growth factor family,
      increases heart rate in experimental animals but its other actions on cardiac
      function and cellular mechanisms responsible for the positive chronotrophic
      effect remain unknown. We have studied the actions of human recombinant gene-2
      relaxin on the release of atrial natriuretic peptide (ANP) and cardiac function
      (heart rate, contractile force, perfusion pressure) as well as the underlying
      signal transduction mechanisms by using the isolated perfused spontaneously
      beating rat heart preparation. The administration of relaxin into the perfusion
      fluid at concentrations of 1.5, 3 or 10 nM for 30 min caused a dose-dependent
      sustained increase in heart rate, while contractile force and perfusion pressure
      remained unchanged. In addition, infusion of relaxin at a concentration of 10 nM
      into the perfusate produced a gradual 1.5-fold increase in immunoreactive ANP (IR
      ANP) secretion (from 456 +/- 76 to 701 +/- 124 pg/ml, F = 4.5, P < 0.001). The
      ANP secretory and chronotrophic effects of relaxin appear to involve the
      activation of protein kinase C, since administration of a protein kinase C
      inhibitor staurosporine at a concentration of 30 nM completely blocked the effect
      of relaxin (10 nM) on IR-ANP secretion (P < 0.001) and heart rate (P < 0.001). A
      cAMP-dependent protein kinase inhibitor, H-89 (100 nM), also substantially
      reduced the ANP secretory effect of relaxin and attenuated the increase in heart
      rate during the sustained phase of the relaxin infusion (P < 0.001). KN-62 (3
      microM), a Ca2+/calmodulin-dependent protein kinase inhibitor, decreased the
      positive chronotrophic effect of relaxin (P < 0.001) but did not influence
      significantly the effect of relaxin on IR-ANP release in isolated perfused rat
      heart preparation. These results provide the first evidence that relaxin
      stimulates the secretion of ANP from isolated perfused rat hearts. Our results
      also suggest that relaxin modulates ANP secretion by activation of protein kinase
      C and cAMP-dependent protein kinase pathways.

PMID- 8882169
TI  - Localization of prostaglandin H synthase type 2 protein and mRNA in term human
      fetal membranes and decidua.
AB  - Prostaglandin (PG) production by human fetal membranes (amnion and chorion laeve)
      may be important in the onset and progression of labour, cervical ripening and
      membrane rupture. Prostaglandin H synthase (PGHS) is a key enzyme in PG formation
      and has two isoforms, a constitutive form (PGHS-1) and an inducible form (PGHS
      2). The present study examined the cellular distribution of the PGHS-2 enzyme and
      PGHS-2 mRNA in term human fetal membranes and decidua prior to and following
      labour, using immunohistochemistry and in situ hybridization with an 35S-labelled
      oligonucleotide probe. The PGHS-2 protein was found to be localized in amnion
      epithelial cells and chorion laeve trophoblast, but was absent or at low levels
      in the decidual stroma in most tissues, although cells surrounding some of the
      blood vessels in the decidual did express PGHS-2. In situ hybridization
      demonstrated that PGHS-2 mRNA had a similar distribution and was localized to
      amnion epithelial cells, cells in the amnion-chorion mesenchyme, chorion laeve
      trophoblast and, occasionally, to cells surrounding blood vessels in the decidua.
      Of particular note was the high mRNA expression in some cells and low expression
      in other cells, particularly in the chorion, and the low level of PGHS-2 mRNA in
      decidua. There was no observable difference in the cellular localization of PGHS
      2 protein or PGHS-2 mRNA in tissues obtained prior to and following labour. The
      studies indicate that, at term, the inducible form of PGHS, PGHS-2, is expressed
      at a high level in fetal tissues in a number of different cell types rather than
      in the maternal decidua.

PMID- 8882171
TI  - Labour-associated increase in interleukin-1 alpha release in vitro by human
      gestational tissues.
AB  - The aims of this study were to investigate the concentration and release of
      interleukin-1 alpha (IL-1 alpha) at the time of human term labour, and to study
      the regulation of IL-1 alpha release from human gestational tissue explants by
      bacterial endotoxin. Immunoreactive IL-1 alpha concentrations in maternal plasma,
      amniotic fluid and conditioned media from human amniotic fluid and conditioned
      media from human amniotic, choriodecidual and placental explants were quantified
      before and after spontaneous term labour-onset and delivery. Furthermore, the
      effects of a bacterial endotoxin, lipopolysaccharide (LPS), on the release of IL
      1 alpha from human gestational tissue explants over a time course of 24 h (n = 3)
      and LPS concentrations ranging from 10-10(7) pg/ml (n = 3) were investigated. IL
      1 alpha concentrations in maternal plasma and amniotic fluid did not change
      significantly with spontaneous term labour-onset. In contrast, IL-1 alpha was
      released in detectable amounts from human amniotic and choriodecidual explants
      only in association with term labour-onset and delivery. Similarly, placental
      release of IL-1 alpha was increased significantly in explant cultures in
      association with term labour-onset and delivery. LPS increased IL-1 alpha release
      significantly only from human placental explants from both term not-in-labour and
      term after-labour tissues. The data demonstrate differential regulation of IL-1
      alpha release from human gestational tissues in association with labour and LPS
      treatment and the observations support the hypothesis that the labour-associated
      increase in IL-1 alpha release from the fetal membranes is independent of
      exposure to bacterial endotoxin.

PMID- 8882170
TI  - Application of a CHO cell line transfected with the human FSH receptor for the
      measurement of specific FSH receptor activation inhibitors in human serum.
AB  - Effects of FSH on ovarian follicular development can be modulated by factors
      present in serum or by locally produced factors in follicular fluid. Some of
      these factors may act directly on the FSH receptor. A Chinese hamster ovary cell
      line (CHO-F3B4) stably transfected with the human FSH receptor has been used to
      measure the effects of these modulators on FSH-stimulated adenylate cyclase
      activity. After incubation of CHO-F3B4 cells with human recombinant FSH (recFSH)
      for 4 h, cAMP levels were elevated 100-230 times above basal levels (ED50 24.9
      mU/ml recFSH). cAMP production was inhibited after the addition of increasing
      amounts (up to 90% of the incubation volume) of hypogonadotrophic human serum
      (HS) at a fixed stimulatory dose of 30 mU/ml recFSH. At 10% HS the cAMP response
      was diminished to approximately 40-60% of the original value, whereas at a
      concentration of 90% HS the cAMP values were diminished to 30%. Effects of serum
      components on cell viability could be excluded, since forskolin- and cholera
      toxin-stimulated cAMP production were not affected by preincubation of the cells
      in the presence of HS. The FSH-stimulated oestradiol production in rat Sertoli
      cells, which has been used frequently for in vitro bioassays of FSH, was almost
      completely inhibited by the addition of human serum, suggesting that serum has
      more pronounced effects on events downstream of receptor activation. Various
      specific FSH binding inhibitors have been demonstrated by radioreceptor assays to
      be present in serum. In order to assess whether such FSH receptor binding
      inhibitors would also inhibit receptor activation, the specific conditions used
      in the radioreceptor assays (buffers of low ionic strength) were also used to
      measure the effects of serum on FSH receptor activation. Under these conditions
      (a low-salt buffer, corrected for low osmolarity with 200 mM sucrose), CHO-F3B4
      cells responded to FSH stimulation in a similar way to that observed in normal
      buffers. When CHO-F3B4 cells were incubated in this low-salt buffer with a fixed
      low dose of FSH (3 mU/ml), the addition of 3-90% (v/v) dialysed HS inhibited the
      FSH-stimulated cAMP accumulation to a similar extent to that in standard
      conditions. The observed inhibition of adenylate cyclase activation by the low
      molecular-mass fraction (< 10 kDa) of HS could be attributed to the presence of
      salts in this fraction, since the addition of PBS in similar concentrations
      displayed an equal degree of inhibition. It is concluded that the inhibitory
      effects of serum on FSH-stimulated cAMP production in CHO-F3B4 cells are small,
      compared with the inhibition of aromatase induction in rat Sertoli cells. The
      strong inhibition of aromatase in rat Sertoli cells may result from the effects
      of serum acting on the FSH receptors as well as on other pathways not related to
      the FSH receptor. Therefore, measurement of aromatase in Sertoli cells is not
      suitable for the detection of inhibitors of FSH receptor activation. The CHO-F3B4
      cells are useful for the measurement of whether inhibition of FSH receptor
      activation occurs in serum or follicular fluid from patients with disturbed
      follicle development.

PMID- 8882172
TI  - Geographical information systems and tropical diseases.

PMID- 8882173
TI  - Royal Society of Tropical Medicine and Hygiene meeting at Manson House, London,
      18 May 1995. The epidemiology of human schistosomiasis in the Senegal river
      basin.
AB  - Extensive water development has taken place in the north of Senegal over the last
      decade, resulting in a large increase in the amount of fresh water for
      irrigation. The objectives of the present study were to determine the prevalence
      and intensity of Schistosoma mansoni and S. haematobium in the Senegal river
      basin (SRB), and to ascertain the distribution of the snail species acting as
      intermediate hosts for both species of schistosomes. The schistosomiasis survey
      started in January 1994 and was completed in March 1995. Compared to studies
      before the construction of the Diama dam, there was a significant increase in
      both the prevalence and intensity of urinary and intestinal schistosomiasis in
      the human population in parts of the SRB. From the 9014 people who were
      registered from 180 villages and 4 towns (10 districts), 7750 were examined. S.
      mansoni was found in the lower valley (lower delta-Senegal river, lower delta
      Lampsar river, upper delta, and diere) but not in the middle valley. The mean
      prevalence ranged from 4.4% in the lower delta-Senegal River to 71.8% in the zone
      of Lac de Guiers, where prevalence and intensity of infection were higher on the
      eastern side of the lake (81.3% with a mean number of 2088 eggs/g of faeces)
      compared with the western side (50.3% with a mean 1111 eggs/g). S. haematobium
      was recorded throughout the area of study, ranging from a mean prevalence of
      0.37% in diere (lower valley) to 41.5% in the lower valley (Lampsar river), where
      the mean egg count was 313/10 mL of urine. Physical and chemical changes to the
      environment have favoured the spread and increase in the populations of
      freshwater snails. The only snail involved in the transmission of S. mansoni was
      Biomphalaria pfeifferi. Five species of bulinid snails were present--Bulinus
      globosus, Bu. umbilicatus, Bu. senegalensis, Bu. forskalii and Bu. truncatus--but
      only the first 3 species were involved in the transmission of S. haematobium in
      the lower and middle valleys.

PMID- 8882174
TI  - Royal Society of Tropical Medicine and Hygiene meeting at Manson House, London,
      14 December 1995. Enteropathogenic Escherichia coli--mucosal infection models.
AB  - The formation of attaching and effacing (A/E) lesions is central to the
      pathogenesis of enteropathogenic Escherichia coli (EPEC)-mediated disease in
      humans and Citrobacter rodentium-mediated transmissible colonic hyperplasia in
      mice. Closely related outer membrane proteins, known as intimins, are required
      for formation of the A/E lesion by both EPEC and C. rodentium. In this study we
      found similar ultrastructural damage in small intestinal biopsies from an EPEC
      infected child and large bowel specimens from C. rodentium-infected mice. The C.
      rodentium-infected large bowel biopsies revealed massive hyperplastic reactions
      and the infected human small intestinal biopsies showed an increase in total
      crypt cell number and mitotic index. EPEC-infected small intestinal organ
      cultures revealed bacteria adhering in a localized pattern and evidence of A/E
      lesions. Covaspheres coated with a biologically active cell-binding domain of
      intimin also adhered to cells in a localized fashion but did not induce the
      characteristic A/E lesions.

PMID- 8882176
TI  - Who misses out with school-based health programmes? a study of schistosomiasis
      control in Egypt.
AB  - There has been a recent revival of interest in school-based health programmes in
      developing countries as a means of reducing the morbidity observed in school-aged
      children, of improving their physical growth and cognitive development, and of
      controlling transmission of disease in the community at large. This study used
      data collected from a large epidemiological survey of schistosomiasis in Egypt to
      examine what proportion of infected children missed treatment from an established
      national school-based schistosomiasis control programme simply because they did
      not attend school. It showed that children who were not enrolled in school had a
      higher prevalence of infection and were more intensely infected than children who
      attended school. At the extreme, over 80% of infected girls in one part of Egypt
      could not be treated by the existing school programme because they did not attend
      school. If these trends are similar in other countries where school-based
      programmes are being developed, school-based delivery may exacerbate existing
      inequalities in society and ways of expanding services to children who do not
      attend school regularly need to be explored.

PMID- 8882175
TI  - Pyrethroid-impregnated bed nets for personal protection against malaria for
      Afghan refugees.
AB  - A field trial of permethrin-impregnated bed nets (PIBs) was conducted in 2 Afghan
      refugee villages in Pakistan. Nets were issued to only 10% of families (= 1398
      people); this simulated a situation in which bed nets are gradually adopted by
      villagers in Afghanistan. A further 10% lacking bed nets were selected as
      controls from the same villages. An initial survey showed that 86% of household
      heads were aware that malaria was transmitted by mosquito bites, but only 2% had
      used bed nets before. Trial families were encouraged to attend the village health
      centres if they fell ill. Microscopy records showed that, between July and
      December 1991, 22.4% of the control group became infected with Plasmodium vivax
      and 13.0% contracted P. falciparum while in the intervention group only 9.9%
      contracted P. vivax (relative risk 0.58, confidence interval [CI] 95% 0.49-0.68)
      and only 3.8% contracted P. falciparum (relative risk 0.39, 95% CI 0.29-0.53). A
      single treatment of the nets with permethrin at 0.5g/m2 remained protective
      throughout the 6 months' transmission season. 73% of families claimed to use
      their nets every night; members of families who claimed to use nets less
      regularly showed an incidence similar to that of the control group. There was no
      sex or age difference in net use or protective efficacy. Headlouse infestation
      rates were reduced in PIB users. Few nets were washed, given away or sold. The
      prospect for PIBs as personal protection appears good, despite people's lack of
      previous experience.

PMID- 8882177
TI  - Measuring the effect of a hygiene behaviour intervention by indicators of
      behaviour and diarrhoeal disease.
AB  - A social marketing approach used both qualitative and quantitative methods to
      develop a hygiene behaviour intervention in rural north-east Thailand. Behaviours
      were preselected from a previous study and the intervention was designed to
      promote hand washing, especially before feeding a baby, cooking, eating, and
      after defaecation or cleaning a baby's bottom, and dish washing immediately after
      eating. A bacteriological indicator (enumerating faecal streptococci using a
      finger impression technique) was developed to measure changes in hand washing
      behaviour and observation (spot checks) of dirty dishes to indicate dish washing
      practice. There was a significant improvement in both behaviours and a
      significant reduction in diarrhoeal disease as a result of the intervention.
      Furthermore, both indicators were retrospectively found to be positively related
      to diarrhoeal disease incidence. However, receiving and being able to recall the
      intervention messages was not necessarily sufficient to ensure behaviour change,
      as some adults found it difficult to change old habits. Villages showing the
      greatest improvement tended to have a stronger sense of community than others and
      to have more people actively involved in the intervention.

PMID- 8882178
TI  - Comparative evaluation of the use of artificial neural networks for modelling the
      epidemiology of schistosomiasis mansoni.
AB  - There has been a marked increase in the application of approaches based on
      artificial intelligence (AI) in the field of computer science and medical
      diagnosis, but AI is still relatively unused in epidemiological settings. In this
      study we report results of the application of neural networks (NN; a special
      category of AI) to schistosomiasis. It was possible to design an NN structure
      which can process and fit epidemiological data collected from 251 schoolchildren
      in Egypt using the first year's data to predict second and third years' infection
      rates. Data collected over 3 years included age, gender, exposure to canal water
      and agricultural activities, medical history and examination, and stool and urine
      parasitology. Schistosoma mansoni infection rates were 50%, 78% and 66% at the
      baseline and the 2 follow-up periods, respectively. NN modelling was based on the
      standard back-propagation algorithm, in which we built a suitable configuration
      of the network, using the first year's data, that optimized performance. It was
      implemented on an IBM compatible computer using commercially available software.
      The performance of the NN model in the first year compared favourably with
      logistic regression (NN sensitivity = 83% (95% confidence interval [CI] 78-88%)
      and positive predictive value (PPV) = 63% (95% CI 57-69%); logistic regression
      sensitivity = 66% (95% CI 60%-72%) and PPV = 59% (95% CI 53%-65%). The NN model
      generalized the criteria for predicting infection over time better than logistic
      regression and showed more stability over time, as it retained its sensitivity
      and specificity and had better false positive and negative profiles than logistic
      regression. The potential of NN-based models to analyse and predict wide-scale
      control programme data, which are inevitably based on unstable egg excretion
      rates and insensitive laboratory techniques, is promising but still untapped.

PMID- 8882179
TI  - Influenza survey in Senegal.

PMID- 8882180
TI  - Epidemiological features of epidemic cholera (El Tor) in Zimbabwe.
AB  - Epidemics of cholera have been frequent in southern Africa since the
      reintroduction of the disease to the continent in 1970. In late 1992, following a
      severe drought and an influx of refugees from Mozambique, cholera reappeared in
      Zimbabwe for the first time since 1985 and rapidly spread through the rural areas
      of the country. Data relating to symptomatic cholera infection collected during 2
      large outbreaks on the eastern border of the country showed that host age and sex
      were important factors relating to symptomatic infection, as were population
      density and access to water. Epidemic profiles for the 2 study areas differed in
      that one of the profiles exhibited a distinct second phase epidemic. This unusual
      pattern was compared qualitatively with the output of a series of simple
      mathematical models to examine the contribution of different epidemiological
      processes to the pattern of disease observed. Model output suggested a complex
      disease process, in which the dynamics may have been influenced by spatial
      components. Statistical analysis of these unusual data showed that the observed
      pattern was independent of the effects of host age or sex, and provided
      compelling evidence of a marked spatial component of the second phase epidemic.

PMID- 8882181
TI  - Specificity of a commercial indirect immunofluorescence technique in the
      diagnosis of visceral leishmaniasis in patients infected with HIV-1.

PMID- 8882182
TI  - A polymerase chain reaction assay for the detection of Wuchereria bancrofti in
      blood samples from French Polynesia.
AB  - A polymerase chain reaction (PCR) assay based on a highly repeated
      deoxyribonucleic acid (DNA) sequence found in Wuchereria bancrofti (the SspI
      repeat) has been developed to address the shortcomings of traditional diagnostic
      methods. In this field study in a W. bancrofti endemic region of French
      Polynesia, 373 human blood samples were collected and 100 microL of blood were
      screened by the SspI PCR assay and 1 microL by membrane filtration. The SspI PCR
      assay detected 99 of 113 blood samples in which microfilariae had been detected
      by filtration (sensitivity of 88%) with a specificity of 100%. All the samples
      missed by the SspI PCR assay had less than 8 microfilariae per mL of blood. To
      evaluate the efficacy of screening larger blood samples by PCR, both 100 microL
      and 500 microL samples from 50 patients with very low-level microfilaraemia were
      screened by the SspI PCR assay; the sensitivity increased from 60% to 84% when
      using the larger volume of blood. Finally, an enzyme-linked immunosorbent assay
      based version of the SspI PCR assay was used to screen blood from 12 patients
      following treatment with diethylcarbamazine, ivermectin, or both. These results
      showed that the PCR assay closely paralleled the presence or absence of
      microfilariae in the blood and that no increase in the DNA level was seen
      immediately following drug treatment.

PMID- 8882183
TI  - Possible prognostic significance of a brief rise in parasitaemia following
      quinine treatment of severe Plasmodium falciparum malaria.
AB  - An increase in parasitaemia is not uncommon after initiation of treatment for
      Plasmodium falciparum malaria, but its exact significance is unknown. The time
      course of parasitaemia was assessed retrospectively in 33 patients with severe
      imported malaria. In 19 patients (group 1) mean parasitaemia (+/- SEM) fell
      promptly after starting quinine treatment, from 24.9 +/- 4.1% on day 0 to 9.7 +/-
      2.3% on day 1 and 1.8 +/- 0.7% on day 2. In 14 other patients (group 2),
      parasitaemia did not change significantly or increased, with mean parasitaemia
      (+/- SEM) of 9.5 +/- 2.1% on day 0, 17.2 +/- 2.6% on day 1, and 3.7 +/- 1.8% on
      day 2. Simplified acute physiology scores on admission (mean +/- SEM) were 17.4
      +/- 1.4 in group 1 and 11.7 +/- 1.0 in group 2 (P = 0.006). The mean number of
      complications of malaria per patient (+/- SEM) was 2.9 +/- 0.5 in group 1 and 1.6
      +/- 0.3 in group 2 (P = 0.046). Two group 1 patients died. Initially, more than
      95% of peripheral blood parasites were tiny and small rings in both groups, and
      this distribution was unchanged on day 1, suggesting that the parasitaemia
      increase in group 2 was not due to release of sequestered mature parasites. In
      severe falciparum malaria, a rise in parasitaemia after treatment initiation may
      be of favourable prognostic significance and should not lead to aggressive
      therapeutic approaches such as exchange transfusion.

PMID- 8882184
TI  - Absence of neuropsychological sequelae following cerebral malaria in Gambian
      children.
AB  - Cerebral malaria causes major neurological sequelae in a proportion of survivors
      and may lead to neuropsychological sequelae in children who seem to have made a
      good recovery. If this is the case, cerebral malaria could have a dramatic impact
      on the development of thousands of African children. The present study was
      carried out to provide information on the incidence and type of
      neuropsychological sequelae in children who survive the disease without major
      neurological sequelae. A matched case-control study design was used in which 36
      pairs of children were assessed. The cases had been treated for cerebral malaria
      a mean of 3.4 years before testing. No evidence of a serious long-term impact on
      most assessed neuropsychological functions was found in these children. Only in
      the balance test did cases perform less well than their matched controls, but the
      difference between the 2 groups was only of borderline significance. These
      findings suggest that the long-term impact of cerebral malaria on the development
      of children who recover without major neurological sequelae is not as serious as
      had been feared.

PMID- 8882185
TI  - Elevated serum nitrate in Trypanosoma brucei 'rhodesiense' infections: evidence
      for inducible nitric oxide synthesis in trypanosomiasis.

PMID- 8882186
TI  - Diffuse cutaneous leishmaniasis due to Leishmania major in Senegal.

PMID- 8882187
TI  - Schistosoma haematobium infection in western Madagascar: morbidity determined by
      ultrasonography.
AB  - To assess the morbidity related to Schistosoma haematobium infection in western
      Madagascar, an ultrasonographic examination was performed of 574 inhabitants > 5
      years old in a village in an old-established endemic area where no prior
      systematic antischistosomal treatment had been given. The overall prevalence of
      infection was 75.9% and the geometric mean egg count of positive individuals was
      36 eggs/10 mL of urine. Recent haematuria had been experienced by 31.8% of
      individuals. Echographic abnormalities of the urinary tract were present in 50.5%
      of individuals: they were more frequent in males. Bladder wall lesions were
      observed in 93.1% of individuals with ultrasonographic changes, irregularities of
      the inner surface being the most common finding. Congestive changes were noted in
      8.4% of kidneys, but we observed only 4 severe congestions. Bladder lesions and
      congestive changes in kidneys predominated in youth; their presence and severity
      were significantly correlated with egg excretion. In 12 inhabitants, grade 1
      periportal fibrosis was observed, but no significant association was found with
      S. haematobium infection. In a control village, where the prevalence of S.
      haematobium infection was 7%, moderate congestion of kidneys was observed in 2%
      of examined inhabitants, and bladder changes in 6%, with a significant
      relationship with S. haematobium infection.

PMID- 8882188
TI  - Clinical features, antimicrobial susceptibility and toxin production in Vibrio
      cholerae O139 infection: comparison with V. cholerae O1 infection.
AB  - We prospectively compared the clinical features of cholera due to Vibrio cholerae
      O1 and V. cholerae O139 in 242 men 18-60 years of age, with a history of
      diarrhoea of 24 h or less, and moderate or severe dehydration. The antimicrobial
      susceptibility of all of the V. cholerae strains isolated from these patients was
      determined, and in vitro cholera toxin production determined for 68 isolates. On
      admission, the 110 patients infected with V. cholerae O1 significantly more often
      had body temperature < 36 degrees C (85% vs. 66%, P < or = 0.05), faecal
      leucocyte count > 50/high power microscope field (40% vs. 12%), and lower mean
      faecal chloride content (94 vs. 103 mmol/L) than did the 132 patients infected
      with V. cholerae O139. Patients infected with V. cholerae O1 also initially had
      significantly higher median volumes of stool (13 vs. 11 mL per kg body weight per
      h), vomitus (1 mL/kg/h vs. nil), and intravenous fluid requirements (23 vs. 21
      mL/kg/h). All V. cholerae O1 and O139 isolates were susceptible to ciprofloxacin,
      all but one were susceptible to doxycycline and erythromycin, and the majority of
      both serogroups were resistant to co-trimoxazole (95% and 97%, respectively). V.
      cholerae O1 and O139 susceptibilities differed for tetracycline (58% vs. 100%)
      and furazolidone (27% vs. 93%) (P < 0.001 in both cases). The amount of cholera
      toxin produced in vitro by strains of V. cholerae O1 and O139 was similar, and
      did not correlate with stool volume. The results demonstrated that V. cholerae
      O139 does not cause more severe, or more invasive, disease than V. cholerae O1,
      as had been previously suggested, but that clinically important differences in
      antimicrobial susceptibility do exist among strains isolated in Bangladesh.

PMID- 8882189
TI  - Infections in haematological malignancies: an autopsy study of 72 cases.
AB  - Autopsy material from 72 patients with haematological malignancies treated in
      India was reviewed. Thirty-seven patients (51%) had documented infections; 20
      (27%) had bacterial infections, 14 of which were Gram-negative organisms
      (Pseudomonas species in 10); tuberculosis was present in 2 patients (2.7%).
      Twenty-one patients (29%) had systemic fungal infections; invasive pulmonary
      aspergillosis and gastrointestinal candidiasis were present in 10 patients each.
      Only 3 patients (4%) had viral infection, all of which were due to
      cytomegalovirus. Eleven patients (15%) had polymicrobial infections. No patient
      had any parasitic infection. Systemic fungal infections due to Aspergillus and
      Candida predominated, while Gram-negative bacterial infections were also common.

PMID- 8882190
TI  - Survey of resistance to chloroquine by Plasmodium vivax in Indonesia.
AB  - In February 1995 we surveyed to chloroquine among patients with Plasmodium vivax
      malaria at Nias Island, in the Indian Ocean near north-western Sumatra, Indonesa.
      The subjects, 21 indigenous males and females (6-50 years old) infected with > 40
      asexual blood stage parasites of P. vivax per microliter of blood, had mild
      symptoms or none at all. Seven of these patients had > 100 ng/mL whole blood
      chloroquine levels before the first supervised dose of chloroquine (3 doses of 10
      mg/kg, 10 mg/kg, 5 mg/kg of base given at 24 h intervals). Whole blood
      chloroquine levels on the last day of dosing confirmed normal absorption (range
      413-3248, mean 1141, SD 616 ng/mL). Blood films were examined on days 0, 2, 4, 7,
      11, 14, 18, 21 and 28 after initiating therapy. Three patients had recurrent
      asexual P. vivax parasitaemias between days 14 and 18, despite effective levels
      of chloroquine in whole blood (> or = 100 ng/mL) at the time of recurrence.
      Resistance to standard chloroquine therapy by P. vivax appeared in 14% of
      infections among residents of Nias.

PMID- 8882191
TI  - Chloroquine sensitive Plasmodium falciparum and P. vivax in central Java,
      Indonesia.

PMID- 8882192
TI  - Survey of resistance to chloroquine of falciparum and vivax malaria in Palawan,
      The Philippines.

PMID- 8882193
TI  - Artemether or artesunate followed by mefloquine as a possible treatment for
      multidrug resistant falciparum malaria.
AB  - Plasmodium falciparum in south-east Asia is highly resistant to chloroquine and
      sulfadoxine-pyrimethamine. Mefloquine used to be the chemosuppressant drug of
      choice in areas with chloroquine resistance. However, sensitivity to this drug
      has recently decreased in Thailand, Cambodia and Myanmar, and there is no
      suitable single alternative drug. We therefore investigated possible alternative
      combination therapies for multidrug resistant falciparum malaria. 120 male Thai
      patients at Makarm Malaria Clinic, Chantaburi, in eastern Thailand were allocated
      at random to receive either oral artemether (group A) or artesunate (group B) at
      a single dose of 300 mg on day 1, both followed by mefloquine, 750 and 500 mg at
      24 and 30 h, respectively. Follow-up was on days 1, 2, 7, 14, 21, 28, 35 and 42.
      Patients in both groups had a rapid initial response to treatment; in most cases
      parasitaemia was cleared within 24 h, and fever was cleared within 24 h in 62%
      and 76.7% of the patients in groups A and B, respectively. 58 patients in group A
      and 57 in group B completed follow-up and cure rates were 98% and 97%,
      respectively. Reinfection could not be excluded for the 3 patients with
      recrudescences; all were cured with a repeated course of treatment. No serious
      adverse effect was observed in either group, only mild and transient nausea,
      vomiting and loss of appetite, with no significant difference between the 2
      groups. These results suggest that a single oral dose of 300 mg of either
      artemether or artesunate followed by 1250 mg of mefloquine in 2 divided doses is
      effective against multiple drug resistant falciparum malaria. Either regimen can
      be considered as a suitable 'stand-by' in endemic areas of multiple drug
      resistant falciparum malaria.

PMID- 8882195
TI  - Metronidazole and suramin combination in the treatment of arsenical refractory
      Rhodesian sleeping sickness--a case study.

PMID- 8882194
TI  - Proguanil polymorphism does not affect the antimalarial activity of proguanil
      combined with atovaquone in vitro.
AB  - Clinical studies have shown proguanil (PROG) combined with atovaquone (ATQ) to be
      an effective and safe antimalarial combination for the treatment of multidrug
      resistant falciparum malaria. PROG is a prodrug, which undergoes hepatic
      metabolism to its pharmacologically active metabolite cycloguanil (CYC).
      Individuals exhibit genetic polymorphism with respect to PROG, and can be
      phenotyped as either extensive metabolizers (EMs) or poor metabolizers (PMs) by
      measuring their PROG/CYC concentration ratio in plasma following PROG/ATQ
      administration. PMs produce lower plasma concentrations of CYC than EMs and thus
      may be more susceptible to prophylaxis or treatment failure. Both PROG and CYC
      potentiate the activity of ATQ in vitro. The antimalarial activity ex vivo of
      Thai patients' plasma samples obtained from EMs and PMs given concurrent PROG and
      ATQ was studied using the K1 isolate of Plasmodium falciparum. This isolate is
      resistant to PROG and CYC, but sensitive to ATQ. Maximum inhibitory dilution
      profiles of the patients' plasma samples containing PROG and ATQ from EMs and PMs
      were similar. These findings indicate that differences in plasma drug
      concentrations between EMs and PMs did not alter the antimalarial activity in
      vitro against the K1 isolate. The phenotypic status of individuals is not an
      important issue in the treatment of patients with PROG/ATQ.

PMID- 8882197
TI  - Decreased prevalence and intensity of Loa loa infection in a community treated
      with ivermectin every three months for two years.

PMID- 8882196
TI  - Mass DEC chemotherapy for control of bancroftian filariasis: comparative efficacy
      of four strategies two years after start of treatment.
AB  - The efficacy of 4 strategies for control of bancroftian filariasis using mass
      diethylcarbamazine (DEC) chemotherapy was evaluated and compared in 4 endemic
      communities in Tanzania 2 years after the start of treatment. The strategies used
      were the standard 12 d treatment (strategy I), a semi-annual single dose
      treatment (strategy II), a monthly low dose treatment (strategy III), and DEC
      medicated salt (strategy IV). Treatment took place during the first study year,
      and no treatment was given during the second year. Among individuals who were
      microfilaraemic before treatment, the microfilaria (mf) clearance rates were
      41.5%, 75.0%, 84.0% and 89.1%, and the pre-treatment mf geometric mean
      intensities (GMIs) were reduced by 97.1%, 98.9%, 99.8% and 99.8%, for strategies
      I, II, III and IV, respectively, 2 years after starting treatment. Statistical
      analysis indicated that strategies III and IV were equally effective, and
      superior in clearing microfilaraemias and in reducing mf GMIs compared to
      strategies I and II; strategy II was significantly more effective than strategy
      I. The rate of occurrence of new cases of microfilaraemia among individuals who
      were amicrofilaraemic during the pre-treatment surveys was negligible over the
      study period in all communities. In all the communities combined, 66.6% of males
      presenting hydrocele before treatment, and 61.5% of individuals presenting
      elephantiasis before treatment, showed improvements in these conditions 2 years
      after the start of treatment, either as a reduction in size or complete
      disappearance.

PMID- 8882198
TI  - Blood, bone marrow and splenic lymphocyte subset profiles in Indian visceral
      leishmaniasis.
AB  - We examined the lymphocyte subsets in peripheral blood, bone marrow and spleen of
      11 patients with acute visceral leishmaniasis (VL) and 9 with chronic VL before
      and after 8 weeks of antileishmanial therapy. On admission, the CD4 cell count
      was depressed in the peripheral blood of acute and chronic VL cases as compared
      to the value in 10 normal control subjects. In contrast, CD4 cell counts were
      higher in the bone marrow in acute and chronic cases, and in splenic aspirates of
      chronic cases only, compared to normal values. The peripheral blood CD8 cell
      count, while normal in acute cases, was uniformly low in chronic cases. Counts of
      CD8 cells were also low in bone marrow of acute and chronic cases, as well as in
      splenic aspirates of chronic cases only. All these differences were significant
      (P < 0.05). After treatment, the CD4 cell count in the peripheral blood
      increased, but decreased in bone marrow and splenic aspirates. The CD8 cell count
      remained unaltered in the peripheral blood but increased significantly (P < 0.05)
      in bone marrow and spleen. The results suggest that in VL the peripheral blood
      picture may not reveal the actual T cell subset profile in the
      reticuloendothelial system. The changes in CD8 cell counts in the bone marrow and
      spleen seem to be independent, and are probably influenced by antileishmanial
      therapy.

PMID- 8882199
TI  - Prolonged Th2 cell activation and increased viral replication in HIV-Leishmania
      co-infected patients despite treatment.

PMID- 8882200
TI  - Vaccination against hepatitis B virus in highly endemic areas: waning vaccine
      induced immunity and the need for booster doses.
AB  - A dynamic model of the transmission of hepatitis B virus (HBV) was used to
      investigate some of the possible implications of the loss of vaccine-induced
      immunity on the effectiveness of mass HBV vaccination in high endemicity
      countries. The model, which describes the processes of horizontal and vertical
      transmission of HBV in a rapidly growing population, was based on one previously
      published, modified to allow for waning vaccine-induced immunity. All model
      parameters were empirically based. Summaries of published data provided estimates
      of the mean duration of immunity in vaccine responders and age-dependence in the
      risk of developing acute HBV disease. Simulations of the temporal and long-term
      impact of mass infant immunization on the prevalence of HBV chronic carriage and
      acute disease suggested that booster doses are of little benefit in coping with
      waning vaccine protection. The key factor is that vaccine-induced protection
      should be long enough to prevent infection in the first few years of life, when
      the risk of developing chronic carriage is highest.

PMID- 8882201
TI  - Measles vaccine failure not associated with vitamin A supplementation.

PMID- 8882202
TI  - Seasonal change in nutritional status among young children in an urban shanty
      town in Peru.
AB  - Seasonal variation in nutritional status among young children has been described
      in rural populations, but in few urban settings. We examined seasonality in 7
      years of nutritional surveillance data from an urban shanty town near Lima, Peru,
      where children 0-35 months old were measured at intervals of 4-5 months. We
      compared nutritional status by month, using generalized estimating equations to
      account for the intercorrelations among measurements of the same person at
      different times. The periodicity of the seasonal variation was found to fit a
      model in which the month of the year was sine-transformed, and this sine
      transformed model was used to examine possible interactions with age, sex and
      year of examination. A total of 38,626 measurements was available from 11,333
      children. In late winter, mean weight-for-height was an estimated 0.38 Z score
      higher than in late summer. The seasonal effect occurred at all ages, in both
      sexes, and in each year of surveillance. The amplitude was greatest for children
      6-23 months old. The summer trough in weight-for-height was lower in 1989 than in
      other years; children who experienced this summer low had lower mean height-for
      age in subsequent years. The seasonal variation in nutritional status may be
      related to differences in dietary intake, or to the higher prevalence of
      bacterial diarrhoea in summer than in winter. The more marked drop in weight-for
      height in 1989 and subsequent trough in height-for-age may be related to
      political and economic changes than adversely affected food access in Peru.

PMID- 8882204
TI  - [Evolution of the immunobiologic diagnosis in allergy].

PMID- 8882203
TI  - Clinical diagnosis of malaria.

PMID- 8882205
TI  - Effect of immunotherapy in allergic bronchial asthma.
AB  - A total of 28 patients affected with bronchial asthma were given immunotherapy in
      the allergy clinic of King Fahd Hospital of the University. Of the 28 patients,
      12 were females and 16 were males. IgE titers over 180 IU, skin tests showed
      positive reactions to many allergens mainly inhalant. Treatment with subcutaneous
      injections of immunotherapy was effective.

PMID- 8882206
TI  - [Desensitization, hyposensitization, specific immunotherapy].
AB  - The technique of desensitization began in Great Britain in 1911 (Noon).
      Modifications have recently been introduced in some European countries: in the
      South, desensitization is the cornerstone of treatment of immediate allergy,
      whilst in Scandinavia and especially in Great Britain the number of
      desensitizations has decreased.

PMID- 8882207
TI  - [Multicenter study on the efficacy of Zyrtec (Cetirizine) in the treatment of
      perennial allergic rhinitis in 875 adolescents].
AB  - 875 adolescents of both sexes, aged between 12 and 15 years, who had presented
      with a perennial allergic rhinitis, were included in an open study that was
      conducted by pediatricians and allergologists on the efficacy of ZYRTEC
      (CETIRIZINE). There were four evaluations in the study, at Day-10, D 0, D15 and
      D30 and it was conducted according to the following plan: A first period (D-10 to
      D 0) to establish the eligibility of the subjects to be tested, and to establish
      the clinical allergic history, before definitive inclusion at D 0. A second
      period, of therapy, of 30 days, during which the subjects took a 10 mg tablet of
      ZYRTEC as a daily dose. Efficacy was evaluated at each visit by scores of
      intensity of major symptoms (sneezing, nasal discharge, nasal obstruction, nasal
      pruritus) and secondary symptoms (ocular score ... ) of rhinitis, as well as
      anterior rhinoscopy. The patients made an auto-evaluation of symptoms at
      different times. Analysis of the different parameters showed a real efficacy of
      ZYRTEC, for 30 days of treatment, in young patients. Furthermore, the tolerance
      of the product is excellent. This study has shown an overall improvement in the
      symptoms of perennial allergic rhinitis in patients who were treated with ZYRTEC
      in conditions similar to those of usual medical practice by pediatricians and
      allergologists.

PMID- 8882208
TI  - Hypertonic saline in cystic fibrosis.

PMID- 8882209
TI  - A step forward in clinically evaluating gas transfer in the lung.

PMID- 8882210
TI  - Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic
      fibrosis.
AB  - Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick
      secretions, which cause airway obstruction and subsequent colonization and
      infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase
      has been shown to reduce the viscoelasticity of sputum in patients with cystic
      fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline
      (HS) has been demonstrated to enhance mucociliary clearance and sputum
      expectoration by rehydrating airway secretions, and may therefore provide a low
      cost alternative. We studied the changes in pulmonary function and symptoms in a
      group of patients with CF who have moderate to severe lung disease. The patients
      were evaluated following 2 weeks of treatment with HS in an open-label study.
      Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6%
      NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a
      portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of
      salbutamol was administered prior to the nebulized solutions. A symptom score was
      recorded and spirometry was performed on day 0 before therapy was started, on day
      14 (the last day of therapy), and on day 28 (14 days after the last treatment
      with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2
      (range 7-36) years completed the study. There was no difference in baseline
      characteristics between the two groups. Following 2 weeks of treatment, there was
      a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD)
      in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS
      therapy (P = 0.004). Furthermore, there was a subjective improvement in the
      effectiveness of chest physiotherapy as reported by those using HS (P = 0.02).
      The treatment was well tolerated. We conclude that in patients with CF,
      ultrasonically nebulized hypertonic saline improves lung function in a way
      similar to that reported for human recombinant DNase when inhaled over a 2 week
      period. Nebulized saline also enhances the perception of effectiveness of chest
      physiotherapy.

PMID- 8882211
TI  - Pulmonary diffusing capacity at reduced alveolar volumes in children.
AB  - The diffusing capacity, when normalized per liter of alveolar volume (DL,CO/VA)
      decreases in normal adults, whereas their total diffusing capacity (DL,CO)
      increases as alveolar volume (VA) increases. We studied these relationships in a
      group of normal children below 20 years of age. Diffusion variables were
      determined using the single breath technique. The effects of sex, age, and height
      on these relationships were estimated. DL,CO increased and DL,CO/VA decreased as
      alveolar volume increased. DL,CO and DL,CO/VA reference values at total lung
      capacity (TLC) appeared to be comparable to reference values at TLC in the
      literature. Reference values of DL,CO and DL,CO/VA derived from measurements at
      various alveolar volumes also predict similar values at TLC. The advantage of our
      reference equations is their applicability to patients with restrictive lung
      disease. Actual DL,CO/VA can be compared with reference DL,CO/VA at actual
      (restrictive) TLC instead of reference DL,CO/VA at reference TLC. This comparison
      extends the evaluation of a diffusion disorder.

PMID- 8882212
TI  - Distribution and transmission of Pseudomonas aeruginosa and Burkholderia cepacia
      in a hospital ward.
AB  - Genotyping and antibiotic susceptibility testing were used to analyze Pseudomonas
      aeruginosa and Burkholderia cepacia strains from sink drain from 14 pediatric
      patients with cystic fibrosis (CF) and from hospital personnel as part of a 4
      week prospective study of strain transmission in a pediatric ward. A total of
      87.5% of all washbasin drains were contaminated with P. aeruginosa [10(2) to
      10(5) colony forming units (CFU)/ml sink fluid], whereas B. cepacia was found
      only once in a sink drain. From the eight CF patients already infected with P.
      aeruginosa upon entering the ward, we isolated six genotypes that were identical
      with strains found in sink drains of the ward. Four of the 16 members of the
      personnel had one positive P. aeruginosa hand culture. B. cepacia was never found
      in patients or on personnel hands. Hand washing in contaminated sinks (> or =
      10(3) CFU/ml) led to positive P. aeruginosa or B. cepacia hand cultures. P.
      aeruginosa or B. cepacia embedded in sputum were transmissable by hand shaking
      for up to 180 min, whereas both pathogens suspended in physiological saline were
      transmissable to other hands only up to 30 min. Genotyping of P. aeruginosa
      revealed strain transmission from CF patients or the environment to other
      patients or the personnel, as well as one transmission from the environment to a
      CF patient. The ability of CF sputum to prolong survival of P. aeruginosa and B.
      cepacia may be important for strain transmission. The results suggest that
      improved hygienic measures are required to prevent routes of bacterial
      transmission via the hands and sink drains.

PMID- 8882213
TI  - Tuberculosis in children: an update.

PMID- 8882214
TI  - Pulse oximetry: accuracy of methods of interpreting graphic summaries.
AB  - Although pulse oximetry has been used to determine the frequency and extent of
      hemoglobin desaturation during sleep, movement artifact can result in
      overestimation of desaturation unless valid desaturations can be identified
      accurately. Therefore, we determined the accuracy of pulmonologists' and
      technicians' interpretations of graphic displays of desaturation events, derived
      an objective method for interpreting such events, and validated the method on an
      independent data set. Eighty-seven randomly selected desaturation events were
      classified as valid (58) or artifactual (29) based on cardiorespiratory
      recordings (gold standard) that included pulse waveform and respiratory inductive
      plethysmography signals. Using oximetry recordings (test method), nine pediatric
      pulmonologists and three respiratory technicians ("readers") averaged 50 +/- 11%
      (SD) accuracy for event classification. A single variable, the pulse amplitude
      modulation range (PAMR) prior to desaturation, performed better in discriminating
      valid from artifactual events with 76% accuracy (P < 0.05). Following a seminar
      on oximetry and the use of the PAMR method, the readers' accuracy increased to 73
      +/- 2%. In an independent set of 73 apparent desaturation events (74% valid, 26%
      artifactual), the PAMR method of assessing oximetry graphs yielded 82% accuracy;
      transcutaneous oxygen tension records confirmed a drop in oxygenation during 49
      of 54 (89%) valid desaturation events. In conclusion, the most accurate method
      (91%) of assessing desaturation events requires recording of the pulse and
      respiratory waveforms. However, a practical, easy-to-use method of interpreting
      pulse oximetry recordings achieved 76-82% accuracy, which constitutes a
      significant improvement from previous subjective interpretations.

PMID- 8882215
TI  - Occlusion maneuver to detect the relative contribution of the rib cage and
      abdomen to tidal volume using respiratory inductive plethysmography in infants.
AB  - Respiratory inductive plethysmography (RIP) records movements of the rib cage
      (RC) and abdomen (AB). A calibration procedure is needed to determine their
      relative contribution to tidal volume. We evaluated the hypothesis that the
      relative contribution of the RC and AB could be defined from respiratory efforts
      made during a brief occlusion of the airways in 10 infants aged 6.5-19 months,
      who were studied in quiet sleep. Six occlusions were performed during tidal
      breathing, with and without a pneumotachograph (PNT) and face mask in place. We
      analyzed the periods of occluded respiratory effort when RC and AB were in
      opposite directions (paradoxical movements), plotting RC vs. AB and performing a
      least-squares linear regression to estimate the ratio of the coefficients of
      AB/RC. Multiple linear regression of AB and RC over tidal volume during about 100
      seconds of tidal breathing provided a reference standard. A ratio of 1 means that
      AB and RC make equal contributions to tidal volume. The feasibility of the
      occlusion maneuver was poor; only 51% of occlusions with PNT and 54% without led
      to a paradoxical movement with a good fit (r > 0.9). The mean coefficient of
      variation (range) was 9.35% (3.9-15.3%) with PNT and 12.1% (2.5%-26.3%) without
      it. The accuracy was very poor, with the mean AB/RC value being 0.94 with
      occlusions and 2.39 with multiple linear regression. The mean difference was 1.45
      (SD 0.80), yielding 95% confidence limits for the difference of 0.12-3.01. We
      concluded that, due to its very poor accuracy and feasibility, the occlusion
      technique is not a useful method to calibrate RIP in infancy.

PMID- 8882216
TI  - Multidrug-resistant tuberculosis in children: two cases and a review of the
      literature.

PMID- 8882217
TI  - Airtight pediatric fiberoptic bronchoscopy.

PMID- 8882218
TI  - Health services information and health services research from the British Isles
      to Europe to Asia, over 40 years.

PMID- 8882219
TI  - General practice on a new housing estate. 1956.
AB  - An analysis has been carried out of the records kept for the year 1953 by six
      doctors practising on a new housing estate near London. The population of the
      estate is described in terms of age, sex, and social class. 76 per cent. of the
      registered patients consulted a doctor at some time during the year, the
      consultation rate per person being 4.1 based on the average registered
      population; females had more consultations than males; 80 per cent. of all
      consultations were made by people under the age of 45. One-sixth of the patients
      accounted for about half of the consultations, and 30 per cent. of the
      consultations were made by the 7 per cent. of registered patients who consulted
      twelve or more times in the year. The consultation rates showed a slight, but
      statistically significant, social gradient, with more consultations among
      patients in the lower social classes. The illness rate was 26 per person, and was
      higher among males in infancy and old age, and among females between the ages of
      5 and 64. A method of estimating the duration of sickness in terms of the period
      under medical care was employed. This showed that 70 per cent. of all illnesses
      were dealt with in single consultations, and that only 3 per cent. of illnesses
      were under care for more than 90 days. Over half of the practice population were
      under care for less than 5 days, and only 8 per cent. for more than 90 days. The
      proportion of patients having more than 30 days sickness generally increased with
      age, but there was a slight fall among the women aged 65 and over. Certificates
      were issued at the rate of about one for every five consultations, two-thirds of
      these being necessitated by the requirements of the National Insurance
      regulations. Prescriptions were issued at the rate of about one per consultation,
      the prescription rate being 41 per person. Only 5 per cent. of the practice
      population consulted the doctor but did not obtain a prescription. About 30 per
      cent. of the patients who consulted a doctor were referred outside the practices,
      80 per cent. of all referrals being to hospitals, either as inpatients or as out
      patients. The person-hospital referral rate was 20 per 100, and there were 31
      referrals for every 100 registered patients. Males over 65 had the highest rates
      for consultations, illnesses, prescriptions, and referrals. The reason for this
      is discussed. The value of record-keeping by general practitioners is stressed,
      together with the need for a generally accepted method of expressing rates in
      studies of this kind.

PMID- 8882220
TI  - Quality of life assessment in children: a review of conceptual and methodological
      issues in multidimensional health status measures.
AB  - STUDY OBJECTIVE: To clarify concepts and methodological problems in existing
      multidimensional health status measures for children. DESIGN: Thematic review of
      instruments found by computerised and manual searches, 1979-95. SUBJECTS: Nine
      health status instruments. MAIN RESULTS: Many instruments did not satisfy
      criteria of being child centered or family focussed; few had sufficient
      psychometric properties for research or clinical use; underlying conceptual
      assumptions were rarely explicit. CONCLUSIONS: Quality of life measures should be
      viewed cautiously. Interdisciplinary discussion is required, as well as
      discussion with children and parents, to establish constructs that are truly
      useful.

PMID- 8882221
TI  - Gene environment interaction.

PMID- 8882222
TI  - Further thoughts on the aluminum-Alzheimer's disease link.
AB  - STUDY OBJECTIVE AND METHOD: The results of studies on aluminum (Al) and
      Alzheimer's disease (AD) from groups in Newcastle, UK and Ontario, Canada were
      compared in order to explain why the former were unable to detect a link while
      the latter could, and to suggest alternative ways of examining the data. RESULTS:
      The Al concentrations in the Newcastle study were relatively small compared with
      the Ontario ones. When Al concentrations > 250 micrograms/l were used, the RRs
      were greater for AD than for other forms of dementia, and the RRs were lower for
      those under 75 years and greater at ages 85 years and over than at ages above 75
      years. The relationship between dementia and Al concentrations was U or J shaped-
      there was a minimum at an Al concentration of 100 micrograms/l. Other
      constituents or properties such as silicic acid, fluoride, turbidity, iron, and
      pH all have an effect on the relationship. CONCLUSIONS: Analyses of the type
      reported from Newcastle can yield further information if they are extended to
      include multivariate analyses that take account of other water constituents which
      can affect the relationship between Al water concentrations and AD are carried
      out. The relationship between Al and dementia may be U or J shaped rather than
      linear. With regard to AD, the group aged less than 65 years is not the best one
      in which to explore a relationship. Lastly, it may be that a link with AD is most
      meaningful at relatively high Al water concentrations.

PMID- 8882223
TI  - Changing life expectancy in the 1980s: why was Denmark different from Sweden?
AB  - OBJECTIVE: To identify the contribution from specific causes of death to the
      changes in life expectancy at birth in Denmark relative to Sweden in different
      age groups during the 1980s and to compare the difference in life expectancy
      between the two countries in 1990. DESIGN: Mortality data from WHO mortality
      tapes grouped in smaller series of clinically meaningful categories were used to
      calculate the contribution of each of these categories at each 10 year age group
      to the difference in life expectancy at birth in each country between 1979 and
      1990 and between the two countries. SETTING: Denmark and Sweden. RESULTS: Between
      1979 and 1990 life expectancy increased in both Denmark and Sweden. However, the
      increase in Sweden was more than two years while that in Denmark was less than
      one year. In both countries a decrease in cardiovascular disease mortality
      contributed most to the increase in life expectancy in males as well as females.
      In both sexes the smaller increase in life expectancy in Denmark was a result of
      differences in mortality trends in cardiovascular diseases and respiratory and
      non-respiratory cancers. CONCLUSION: Over a short time two Nordic countries
      experienced remarkable but different changes in mortality. These findings suggest
      that mortality rates are sensitive to even minor differences in social and
      cultural factors across countries and over short time periods.

PMID- 8882224
TI  - Body size and mortality in women: a 29 year follow up of 12,000 pregnant women in
      northern Finland.
AB  - STUDY OBJECTIVE: To examine the association between body height, body mass index
      (BMI), and mortality in fertile women of childbearing age. DESIGN: A prospective
      cohort study with a 29 year mortality follow up. SETTING AND PARTICIPANTS: A
      cohort of women (n = 11,997) expected to deliver during 1966 in two northern
      provinces of Finland. Data on height and pre-pregnancy weight, collected with
      those on sociodemographic characteristics and smoking by questionnaire at the
      third trimester, were provided by 91% of the participants. Follow up for
      mortality using national registries was from delivery until the end of 1994. MAIN
      RESULTS: Height had a 'U' shaped association with total mortality over the whole
      follow up time. In women who were shorter than average, the death rate from
      cardiovascular diseases was increased and in taller women this was true for
      tumours. Compared with the women of 'normal weight' (BMI 21 to < 25 kg/m2), the
      obese subjects (BMI at least 29) did not have increased mortality during the
      first 20 years, but had a relative risk of 1.7 during the final nine years of
      follow up, primarily as a result of cardiovascular diseases. The lean women (BMI
      < 21) experienced a similar rate overall, but moderately overweight women (BMI 25
      to < 29) had a consistently lower mortality than women of normal weight.
      CONCLUSIONS: Among fertile women of childbearing age, both the short and tall
      seem to have an increased total mortality compared with those of average body
      height, resulting from opposite trends in major causes of death. Obesity is
      associated with raised long term total mortality.

PMID- 8882225
TI  - Health and social precursors of unemployment in young men in Great Britain.
AB  - OBJECTIVE: To identify health and socioeconomic factors in childhood that are
      precursors of unemployment in early adult life and to examine the hypothesis that
      young men who become unemployed are more likely to have accumulated risks to
      health during childhood. DESIGN: Longitudinal birth cohort study. The amount of
      unemployment experienced in early adult life up to age 32 years was the outcome
      measure used. Exposure measures to indicate vulnerability to future ill health
      were: height at age 7 years and the Bristol social adjustment guide (BSAG) at age
      11 years, a measure of behavioural maladjustment. Socioeconomic measures were:
      social class at birth, crowding at age 7, qualifications attained before labour
      market entry, and region of residence. SETTING: Great Britain. SUBJECTS:
      Altogether 2256 men with complete data from the national child development study
      (NCDS). The NCDS has collected data on all men and women born in one week in 1958
      and has followed them up using interviews, self completion questionnaires, and
      medical examinations at birth and at ages 7, 11, 16, 23 and 33 years. RESULTS: A
      total of 269 men (11.9%) experienced more than one year of unemployment between
      ages 22 and 32 years. Poor socioeconomic conditions in childhood and a lack of
      qualifications were associated with an increased risk of unemployment.
      Geographical region was also significant in determining the risk of unemployment.
      Men with short stature and poor social adjustment in childhood were more likely
      to experience unemployment in adult life, even after controlling for
      socioeconomic background, education, and parental height. These differences
      remained when those with chronic childhood illnesses were excluded from the
      analysis. The adjusted relative odds for experiencing more than one year of
      unemployment between ages 22 and 32 years for men who were in the top fifth of
      the BSAG distribution (most maladjusted) compared with those in the bottom fifth
      were 2.36 (95% CI 1.49, 3.73). The adjusted relative odds for experiencing more
      than one year of unemployment between ages 22 and 32 years for men who were in
      the bottom fifth of the distribution of height at age 7 years (indicating slowest
      growth) compared with those in the top fifth, were 2.41 (95% CI 1.43, 4.04).
      Adult height was not significantly associated with unemployment. CONCLUSION: The
      relationship between unemployment and poor health arises, in part, because men
      who become unemployed are more likely to have accumulated risks to health during
      childhood, reflected by slower growth and a greater tendency to behavioural
      maladjustment. Short stature in childhood is a significant indicator of poor
      socioeconomic circumstances in childhood and reflects earlier poor development.

PMID- 8882226
TI  - Self rated health as a predictor of coronary heart disease in Copenhagen,
      Denmark.
AB  - STUDY OBJECTIVE: To analyse the association between self rated health and the
      incidence of fatal and non-fatal coronary heart disease (CHD) in a Danish cohort
      followed up over 16 years. DESIGN: This was a prospective epidemiological follow
      up study. SETTING: A cohort from the County of Copenhagen, Denmark. PARTICIPANTS:
      The study included 1052 men and women born in 1936. During the 16 years' follow
      up 50 cases of CHD were registered in either the Danish register of deaths or the
      register of hospital admissions. MAIN RESULTS: Univariate analysis showed the
      following relative risks of CHD in the four self rated health groups: 'extremely
      good': 1.0, 'good': 4.0, 'poor': 5.8, 'miserable': 12.1 (p = 0.02). After control
      for the conventional CHD risk factors and a substantial number of other potential
      confounders the relative risks were: 1.0, 4.2, 6.5, and 18.6 (p = 0.02)
      respectively. CONCLUSIONS: Self rated health was an independent predictor of CHD
      in the present cohort. If confirmed, the association between self rated health
      and CHD may lead to new insight into psychosocial processes leading to this
      disease.

PMID- 8882227
TI  - Mature maternity: long term associations in first children born to older mothers
      in 1970 in the UK.
AB  - STUDY OBJECTIVES: To identify the physical, behavioural, medical, and educational
      outcomes in first children born to women aged 30 or more compared with those born
      to younger women. DESIGN: Longitudinal cohort study design employing logistic
      regression analysis of data obtained from the British births survey of 1970 and
      the child health and education study follow ups to this cohort at ages 5 and 10.
      SETTING: One week birth cohort covering the whole of the United Kingdom.
      PARTICIPANTS: The carers of 4315 first children born to women during the week of
      April 5th-11th 1970 inclusive in the whole of the United Kingdom except Northern
      Ireland, and followed up at both 5 and 10 years of age. In addition, information
      was obtained from health visitors, the child's teacher at 10, and the medical
      officer who completed an examination. At 10 the child also completed a
      questionnaire. MEASUREMENTS: Data were obtained from questionnaires administered
      to the carers of the child at each time point, from their teacher at age 10, and
      from the results of a medical examination at age 10. Educational tests were also
      conducted at this age. MAIN RESULTS: Having adjusted for the effects of
      confounding factors, late primiparity was significantly associated with a number
      of events in labour and delivery involving obstetric interventions ranging from
      induction to operative deliveries and general anaesthesia. At 5 years of age,
      controlling additionally for family size at that time, associations were found
      between late primiparity and fewer adverse measures of behaviour in the child.
      Both the child's head circumference and the score on a picture based vocabulary
      test at this age were slightly greater in the index group. At 10 years of age,
      adjusting for background factors and present family size, late primiparity was
      associated with few outcome measures. Children born to older mothers, however,
      scored slightly higher on a broad range of educational tests administered at
      school. CONCLUSIONS: No clearly demonstrable adverse outcomes could be linked to
      later primiparity in the 1970 child health and education study national cohort
      study. Modest behavioural and educational advantages were detected in the group
      with older first-time mothers. A woman's later primiparity may be associated with
      their child having a slightly larger head circumference compared with whole of
      the rest of the study cohort.

PMID- 8882228
TI  - Epidemiology and implications of ocular trauma admitted to hospital in Scotland.
AB  - OBJECTIVES: To describe the current epidemiology of serious ocular trauma which
      necessitates admission to hospital so that health and safety strategies for the
      prevention of ocular injuries and their role within the national health strategy,
      The Health of the Nation, can be better informed. DESIGN: A prospective
      observational study of all patients with ocular trauma admitted to hospital under
      the care of a consultant ophthalmologist between 1 November 1991 and 31 October
      1992. SETTING: All ophthalmic department in Scotland. SUBJECTS: All patients with
      ocular trauma admitted to hospital in Scotland. The population of Scotland
      represented the population at risk of injury. MEASURES AND MAIN RESULTS: Measures
      included the type and cause of injury, the place where it occurred, and awareness
      of risk and safety. All ophthalmic departments in Scotland participated and 428
      admissions were reported. The home was the most common place for a serious injury
      to occur (30.2%), followed by the workplace (19.6%) and a sports or leisure
      facility (15.8%). The home was the single most frequent place of injury for the 0
      15 year and 65 year and over age groups. Tools or machinery, either at home
      (13.9%) or at work (10.3%), were collectively (24.2%) the most frequent cause of
      injury, followed by assault (21.8%) and sports-related activities (12.5%). The
      most frequent type of injury was a blunt injury (54.4%). Six per cent (n = 25) of
      all injuries were bilateral. Only 13.2% of patients were aware of any risk of
      injury, with 5.6% aware of any risk at home. When applicable, protective eye wear
      was only available to 48.6% of patients and only 19.4% of these used it.
      CONCLUSION: Serious ocular trauma frequently occurs at home and the young and the
      elderly are particularly at risk. This represents a significant change in the
      epidemiology of serious ocular trauma and has important implications for
      prevention. Health and safety strategies specifically aimed at preventing eye
      injury should now include the home as a high risk environment in addition to the
      work-place and sports/leisure facilities. The target groups for accident
      prevention in The Health of the Nation strategy include those at risk of serious
      ocular trauma with potentially sight threatening sequelae. Those involved in
      implementing the national accident prevention strategy should be aware of this,
      for in this process it is possible that some serious eye injuries may also be
      prevented.

PMID- 8882229
TI  - Tobacco smoking and alcohol consumption as risk factors for glioma: a case
      control study in Melbourne, Australia.
AB  - OBJECTIVE: To investigate possible associations between tobacco smoking and
      alcohol consumption and the risk of adult glioma. DESIGN: This was a population
      based, case-control study. Relative risks (RR) were estimated using logistic
      regression analysis. SETTING: Melbourne, Australia. PARTICIPANTS: These comprised
      416 case subjects (166 women, 250 men), 66% of those eligible; and 422 control
      subjects (170 women, 252 men), 43.5% of those potentially eligible. RESULTS:
      There was no increase in risk of glioma with having ever smoked tobacco (RR 1.29,
      95% CI 0.95, 1.75) for all subjects, adjusted for age, a reference date, and
      gender. There was a slight increase in risk for men (RR 1.64, 95% CI 1.1, 2.45),
      but not for women (RR 0.99, 95% CI 0.62, 1.62). For men, there was no increase in
      risk with increasing pack-years of cigarette smoking, but the risk was
      significantly increased in subjects who had smoked for less than 10 years. There
      was no increase in risk associated with having ever drunk alcohol for all
      subjects (RR 0.96, 95% CI 0.67, 1.37), women (RR 0.69, 95% CI 0.4, 1.15) or men
      (RR 1.40, 95% CI 0.81, 2.43). CONCLUSIONS: This study does not support an
      association between either tobacco smoking or alcohol consumption and glioma. The
      pattern of risk associated with tobacco smoking in men appears inconsistent with
      a causal role, and may be due to chance, response bias, or uncontrolled
      confounding.

PMID- 8882230
TI  - The admission of Asian patients to intensive therapy units and its implications
      for kidney donation: a preliminary report from Coventry, UK.
AB  - OBJECTIVE: To determine the relative admission rates of Asian and non-Asian
      patients to intensive therapy units (ITUs) in Coventry and to explore the
      implications of these rates for the transplantation of organs to Asian people.
      DESIGN: Examination of 1991 census data and a retrospective review of ITU
      admissions books. Data were collected on ethnic background, presenting diagnosis,
      and clinical outcome for each admission. SETTING: The three ITUs in Coventry.
      PATIENTS: All admissions to the ITUs from 1990-93 inclusive. RESULTS: Asian
      patients were admitted to ITUs disproportionately to their numbers in the
      Coventry population. Members of the Asian community were less than half as likely
      to be admitted to an ITU (p < 0.001) and more likely to die while there (p =
      0.007) than members of the non-Asian population in Coventry. The proportions of
      patients referred to the transplant unit and the rates of subsequent donation do
      not seem to differ significantly for Asian and non-Asian patients (p = 0.26 in
      both cases). CONCLUSIONS: There are clear implications for the availability of
      cadaveric kidney transplantation to Asian patients, given that few kidneys from
      non-Asian donors are histocompatible with Asian recipients. Indeed, in Asians,
      promotion of living related donation may be more effective in countering the
      organ shortfall than efforts to increase consent to cadaveric transplantation.
      However, it may be valuable to investigate any patterns of morbidity or social or
      cultural factors that might explain the initial low admissions rates to ITUs for
      Asian patients.

PMID- 8882231
TI  - Utilisation of reproductive health services in rural Vietnam; are there equal
      opportunities to plan and protect pregnancies?
AB  - STUDY OBJECTIVES: To describe the utilisation of reproductive health services
      (family planning, antenatal care, and delivery services) and the socioeconomic
      determinants for utilisation of health services. DESIGN: This was a cross
      sectional survey, using a multistage sampling technique. SETTING: Tien Hai
      district, Thai Binh Province, Vietnam. Altogether 1132 mothers with children
      under 5 years of age were interviewed about antenatal, delivery, and family
      planning services utilisation during a five year period (1987-92). MAIN RESULTS:
      Seventy per cent of the women used contraceptive methods, with the intrauterine
      device being the most common. The use of the intrauterine device was positively
      associated with the number of children alive but not with other sociodemographic
      factors in the mothers. Thirty per cent of the women had attended an antenatal
      clinic for check ups during their last pregnancy. It was found that mothers with
      fewer deliveries, higher education, and who were Buddhist or of no religion had
      utilised antenatal services more frequently than the others. Seventy five per
      cent of the mothers in this study had been assisted by health professionals at
      their last delivery. Those mothers with fewer deliveries, higher education, who
      were Buddhist or had no religion, and had sufficient to eat were more likely to
      have their births attended by health professionals. CONCLUSIONS: In spite of a
      relatively high education level in the population and services which are
      generally available, there was an under utilisation of antenatal and delivery
      care and there was no equal opportunity for different groups of mothers to use
      these services. Family planning services were, however, frequently used and were
      used to the same extent by different groups of mothers. Except for abortion,
      alternatives to the intrauterine device method were rarely available. If
      pregnancies are to be protected in an efficient way in rural Vietnam,
      reproductive health care must be strengthened and efforts should be made to reach
      the women who are not using these services at present.

PMID- 8882232
TI  - Non-urgent care in the hospital medical emergency department in France: how much
      and which health needs does it reflect?
AB  - OBJECTIVES: The goal was to describe the use of the medical emergency department
      as a source of non-urgent medical care in order to assess unmet health care needs
      among its users. The specific objectives were thus to assess the proportion of
      emergency department visits for non-urgent medical care and to describe those who
      used the department for this reason. DESIGN: A cross sectional study was
      performed at the emergency department in two hospitals (around 12,000 visits per
      year each). Subjects were interviewed before and after the visit using a
      standardised questionnaire. SETTING: The medical emergency department of two
      university hospitals, one in Paris and one in Besancon (France). SUBJECTS: Each
      patient aged 15 and more attending the emergency department for a visit during 40
      randomly selected periods of 12 hours was included. MAIN OUTCOME MEASURES: A
      definition of urgent care was adopted before the beginning of the study. Four
      expert judgments were then used for each case to determine whether the reason for
      the visit was urgent or not. RESULTS: Altogether 594 patients in the Paris
      emergency department and 614 in the Besancon one were included. In Besancon, the
      patients were older, a general practitioner was more often cited as the regular
      source of care, and the percentage of subsequent hospital admission was higher
      than in Paris (71% versus 34%). The non-urgent visits were estimated to account
      for 35% and 29% of the visits in Paris and Besancon respectively. Patients using
      the emergency department for a non-urgent visit were younger than other patients.
      More of them were unemployed, homeless, born outside of France, and without
      health insurance. CONCLUSIONS: Non-urgent use of the emergency department was
      observed in about one third of the visits. Groups using the department for
      primary care and/or non-urgent care were mostly young and socially fragile, with
      no regular source of health care. Their poor health condition suggests that there
      is a need for a structure providing primary care both inside and outside 'normal'
      working hours.

PMID- 8882233
TI  - Comparison of patient satisfaction with ambulatory visits in competing health
      care delivery settings in Geneva, Switzerland.
AB  - OBJECTIVES: To measure satisfaction with medical visits in various health care
      settings and to assess the extent to which differences in satisfaction scores
      between health care settings can be attributed to patients' characteristics.
      DESIGN: This was a cross sectional survey to measure seven dimensions of patient
      satisfaction. SETTINGS: Ambulatory visits to 'gatekeepers' or specialists in a
      newly established managed care organisation, a private group practice, or a
      university hospital outpatient clinic in Geneva, Switzerland. PATIENTS: There
      were altogether 1027 adult patients (81% participation rate). RESULTS: Patients
      who consulted physicians in the private group practice reported higher levels of
      satisfaction (overall mean 83.2 on a scale between 0 and 100) than university
      clinic patients (79.7), patients of independent specialists within the managed
      plan (78.5), and patients of managed plan gatekeepers (69.8, intergroup
      differences p < 0.001). Differences between settings were reduced after
      adjustment for sex, age, country of origin, general practitioner versus
      specialist visit, and scheduled versus urgent visit (adjusted scores: 80.8, 78.8,
      77.6, and 72.7 in the four settings, p < 0.001). Intergroup differences were
      largest for general satisfaction, but small and non-significant for satisfaction
      with explanations given by the physician and for time spent with the patient.
      CONCLUSIONS: Patient satisfaction varied widely between health care settings.
      Differences in satisfaction ratings could be ascribed only partly to disparities
      in patient populations. Patients of managed plan gatekeepers were least
      satisfied, presumably because they could not choose their physician freely.
      Comparison of patient satisfaction across health care settings can provide a
      basis for targeted quality improvement initiatives.

PMID- 8882234
TI  - Estimating the prevalence of drug misuse in Dundee, Scotland: an application of
      capture-recapture methods.
AB  - STUDY OBJECTIVES: To apply capture-recapture methods to provide an estimate of
      the prevalence of opiate and benzodiazepine misuse in Dundee, Scotland. DESIGN: A
      four sample capture-recapture method using data from both statutory and non
      statutory data sources to estimate drug misuse prevalence in Dundee between
      January 1990 and December 1994. PARTICIPANTS: Users of benzodiazepines or opiates
      residing within Dundee. RESULTS: Altogether 855 drug misusers were identified
      from various sources within Dundee; many were identified from more than one
      source. Using this data, the estimated unknown population was 1702, giving a
      total population of 2557 (95% confidence interval (CI) 1974, 3458) who misuse
      benzodiazepines or opiates. This represents a prevalence of 28.8 (95% CI 22.3,
      39.0) per thousand. CONCLUSIONS: Capture-recapture techniques can be applied to
      statutory and non-statutory agency data to produce an estimate of at least
      certain sections of the drug misusing population. However, it is important to
      recognise the limitations of this methodology and in future to seek to combine a
      range of approaches to the problem of estimating prevalence rather than sticking
      rigidly to any single approach.

PMID- 8882235
TI  - Estimating sample sizes for studies using the SF-36 health survey.

PMID- 8882236
TI  - Suicide from the Clifton Suspension Bridge in England.

PMID- 8882237
TI  - Thoracic epidural analgesia in cardiac surgery.

PMID- 8882238
TI  - An investigation of the potential morphine sparing effect of midazolam.
AB  - The effect of a bolus and continuous infusion of midazolam on postoperative
      morphine consumption was assessed in a placebo-controlled, double-blind, randomly
      allocated trial of 50 patients undergoing elective abdominal hysterectomy.
      Patients in the trial group received a bolus dose of midazolam 5 mg.70 kg-1 at
      induction followed by an infusion at a rate of 1 mg.70 kg-1.h-1 over the next 48
      h. Morphine consumption in the midazolam group was significantly lower in the
      first 12 h postoperatively (p < 0.02) but there was no significant difference
      between the two groups thereafter. Patients in the midazolam treated group had
      lower pain scores over the first 24 h. Also, a significantly greater number of
      patients in the midazolam group required no antiemetic medication over the 48 h
      study period (p < 0.05). Assessment of sedation revealed no significant
      difference between groups. We conclude that low dose midazolam has a significant,
      but short-lived, morphine sparing effect.

PMID- 8882239
TI  - Laryngoscopy using the McCoy laryngoscope after application of a cervical collar.
AB  - A rigid cervical collar was applied to 102 patients under general anaesthesia.
      Laryngoscopy was performed using a McCoy laryngoscope blade (size 3) initially in
      the standard Macintosh configuration followed by activation of the distal hinged
      tip. The two views obtained at laryngoscopy were graded according to standard
      guidelines. In 46/102 (45.1%) patients the laryngoscopic view was improved by one
      or more grades. In 10/102 (9.8%) the view was improved by two grades. Difficult
      laryngoscopy (grade 3 or 4) was encountered in 26/102 patients using the McCoy
      laryngoscope in the unactivated position (Macintosh configuration). Of these 26
      patients, 24 (92.3%) had glottic structures identified (grade 1 or 2) when the
      distal tip of the laryngoscope blade was activated (p < 0.001). The McCoy
      laryngoscope significantly improves the view at laryngoscopy in the patient whose
      neck is immobilised in a rigid cervical collar.

PMID- 8882240
TI  - The effect of the addition of lignocaine on propofol emulsion stability.
AB  - The stability of propofol emulsion following the addition of various amounts of
      lignocaine solution was investigated. The investigations used were macroscopic
      and microscopic observations and electroacoustic determination of both droplet
      size and zeta potential. Evidence of emulsion instability was present following
      the addition of even small amounts of lignocaine. Resultant changes are unlikely
      to be clinically important following the addition of less than 20 mg of
      lignocaine to 200 mg of propofol (20 ml of propofol emulsion). It is recommended,
      however, that anaesthetists consider the possibility of destabilisation of
      propofol emulsion when adding larger doses of lignocaine, or when there is a
      delay between formulation and administration of the propofol-lignocaine mixtures.

PMID- 8882241
TI  - The effect of four different surgical prone positions on cardiovascular
      parameters in healthy volunteers.
AB  - Twenty healthy volunteers were placed in four different surgical prone positions:
      on pillows, on an evacuatable mattress, on pelvic props and in the knee-chest
      position. The normal supine position was used as a control for the measurement of
      cardiovascular parameters. Mean arterial pressure was measured by automated
      oscillotonometry. Transthoracic electrical bioimpedance was used to measure
      cardiac output and heart rate. Cardiac index and total vascular resistance index
      were derived from these data. No significant changes in heart rate or mean
      arterial pressure occurred when the volunteers were moved from the supine
      position to any of the four prone positions or when returned to the supine
      position again. Cardiac index decreased significantly on going from the supine to
      the knee-chest position (20%) and onto the props (17%) but not onto the
      evacuatable mattress (11%) or the pillows (3%).

PMID- 8882242
TI  - Changes in tracheal tube position during laparoscopic cholecystectomy.
AB  - The distance from the carina to the tip of the tracheal tube was measured with a
      fibreoptic bronchoscope in 21 consecutive patients undergoing elective
      laparoscopic cholecystectomy. After placement of an Eschmann tracheal tube with a
      printed intubation guide mark at the vocal cords, the distance was 28 (15) [5-54]
      mm (mean (SD) [range]). The tube was then repositioned so that the distance was
      34 (3) [30-40] mm from tip of the tube to the carina. After creation of
      pneumoperitoneum, the distance was significantly decreased to 26 (5) [17-35] mm
      (p < 0.005), which was not significantly altered by subsequent moving of the
      patient to the reverse Trendelenburg and left lateral tilt position. The maximum
      distance of tube migration was 8 (4) [0-15] mm. Four out of 21 patients would
      have been at risk of bronchial intubation after pneumoperitoneum if the tube had
      not been repositioned. Placement of the tube according to the guide mark is not
      recommended for laparoscopic cholecystectomy.

PMID- 8882243
TI  - The effect of ondansetron on the pharmacokinetics and pharmacodynamics of
      temazepam.
AB  - The objective of this study was to determine the effects of ondansetron on the
      pharmacokinetics of temazepam and on pharmacodynamics relevant to its use as oral
      premedication. Twenty-four healthy volunteers (12 of each sex) were administered
      the following oral treatments in a randomised, double-blind crossover design:
      temazepam 20 mg plus placebo; or temazepam 20 mg plus ondansetron 8 mg. Blood
      samples were taken for plasma temazepam assay at intervals up to 32 h after
      administration. In addition, a brief battery of psychomotor tests was
      administered 1 h prior to dosing and 1 and 4 h after dosing. Analysis of the
      derived pharmacokinetic parameters showed no differences between the treatments
      described above. Analysis of data from the dynamic measures likewise showed no
      difference between the treatments. It was concluded that the co-administration of
      ondansetron did not influence the pharmacokinetics or pharmacodynamic actions of
      temazepam.

PMID- 8882244
TI  - Thiopentone requirements in adults after varying pre-induction doses of fentanyl.
AB  - The thiopentone dose needed for satisfactory induction of anaesthesia was
      determined in 60 adult patients using a double-blinded study design. No
      premedication was given. The effect of pretreatment with four different doses of
      fentanyl on ED50 for thiopentone was determined and compared with a control group
      not receiving fentanyl. The cardiovascular effects of the combinations were also
      studied. ED50 for thiopentone was reduced from 4.0 mg.kg-1 in the control group
      to 2.2 mg.kg-1 in patients receiving fentanyl 5.0 micrograms.kg-1. Only in the
      group of patients receiving fentanyl 5.0 micrograms.kg-1 was there no significant
      change in systolic arterial blood pressure. An increased heart rate was noted in
      patients induced with thiopentone in combination with fentanyl 0.625
      micrograms.kg-1. No adverse effects of thiopentone, fentanyl or the combinations
      were noted.

PMID- 8882245
TI  - The use of absorbent materials for the disposal of controlled drugs.
AB  - The Association of Anaesthetists of Great Britain and Ireland's most recent
      publication on controlled drugs notes that the Environmental Protection Act
      (1992) does not permit the disposal of controlled drugs into the water sewerage
      system. The Association suggests that, in order to conform to the Misuse of Drugs
      Regulations (1985), controlled drugs may best be disposed of using some sort of
      absorbent material, for example a small amount of cat litter or wallpaper paste,
      in the bottom of a sharps bin. The absorbent capacity of three types of cat
      litter, wallpaper paste and a commercial absorbent material were tested. Both the
      commercial absorbent and wallpaper paste displayed limited absorbent qualities
      unless the container was agitated. The cat litter, Snowflake, absorbed more
      controlled drug than the others (one-way ANOVA, F2,12 = 250.85, p < 0.01). The
      use of absorbent materials in sharps bins for the disposal of controlled drugs in
      clinical areas has limitations and may not be suitable. It is concluded,
      therefore, that small volumes of controlled drugs should be disposed of directly
      into clinical waste and that large volumes should be dealt with using a
      commercial absorbent in its own container.

PMID- 8882246
TI  - A new critical incident monitor for use with the paediatric T-piece. In vitro
      evaluation and clinical experience with the Magtrak Infanta Electronic
      Respirometer.
AB  - In vitro studies and clinical evaluation suggest that the Magtrak Infanta
      Electronic respirometer provides a useful additional critical incident monitor
      for use with the paediatric T-piece. During ventilation with the Nuffield 200
      ventilator and Newton valve it provides early warning of leaks or disconnections
      in the breathing system, airway obstruction and reduction in fresh gas flow. Some
      of these events may not be detected by conventional monitors.

PMID- 8882247
TI  - Spinal needle damage during routine clinical practice.
AB  - This study investigated whether the tips of spinal needles are damaged during the
      process of spinal anaesthesia by impact on bone, by repeated attempts at
      performing the block or by the use of an introducer. Used spinal needles from
      five different hospitals were carefully resheathed after use and a questionnaire
      completed. The needles were examined under a light microscope with the observer
      unaware of the questionnaire data. Two hundred and twenty-two needles were
      examined, of which 36 were damaged. Five unused control needles of each type were
      also examined and all were found to be undamaged. There was no significant
      difference between the damaged and undamaged used needles with respect to impacts
      on bone or the number of attempts. Pajunk 24G Sprotte needles were significantly
      less likely to sustain damage when the integral introducer was used as compared
      to an alternative introducer.

PMID- 8882248
TI  - The paradox of the StatCap carbon dioxide indicator. An experimental evaluation
      of rebreathing.
AB  - The StatCap semiquantitative carbon dioxide detector was evaluated in an
      experimental setting. The monitor underread at progressively higher
      concentrations of carbon dioxide. During simulated rebreathing, progressive
      increases in inspired carbon dioxide resulted in the StatCap readings decreasing.
      It is recommended that the StatCap be used with caution in circumstances where
      rebreathing may occur, for example, during manual ventilation with an Ayre's T
      piece.

PMID- 8882249
TI  - The airways and anaesthesia--I. Anatomy, physiology and fluid mechanics.

PMID- 8882250
TI  - Torsade de pointes ventricular tachycardia following coronary artery spasm during
      general anaesthesia.
AB  - We present a patient who suffered two episodes of torsade de pointes ventricular
      tachycardia during general anaesthesia for abdominal surgery. The first occurred
      on suctioning of the tracheobronchial tree and the second while anaesthesia was
      light. Since ST segment elevation was in each case noted before the onset of
      torsade de pointes, coronary artery spasm was suspected to be the cause. An
      intravenous infusion of nitroglycerine was effective in treating and preventing
      these episodes. These findings suggest that coronary artery dilators such as
      nitroglycerine are indicated for initial treatment of torsade de pointes
      following coronary artery spasm in order to facilitate recovery from myocardial
      ischaemia.

PMID- 8882251
TI  - The hazards of anaesthetic gas scavenging systems.
AB  - The function of scavenging equipment is to remove waste anaesthetic gases from
      the operating theatre and thus reduce the potentially harmful effects these
      agents may have on staff. However, these systems can pose a serious risk to
      patients which is not well recognised. We describe two cases where harm to
      patients could have occurred as a result of faulty or inappropriate equipment
      being used and inadequate checking of scavenging systems.

PMID- 8882252
TI  - Osteogenesis imperfecta and malignant hyperthermia. Is there a relationship?
AB  - We describe a patient with osteogenesis imperfecta who developed tachycardia,
      metabolic and respiratory acidosis (pH 7.14, PCO2 8.4 kPa, BE -8.5 mmol.l-1) and
      hyperthermia up to 40 degrees C during anaesthesia with barbiturates, fentanyl,
      pancuronium, and nitrous oxide. Malignant hyperthermia was suspected and the
      patient treated accordingly. Two years later the in-vitro contracture test for
      malignant hyperthermia was completely normal. We conclude that hypermetabolism in
      patients with osteogenesis imperfecta is due to unknown mechanisms other than
      malignant hyperthermia.

PMID- 8882253
TI  - Remote controlled prolonged conscious sedation for gynaecological radiotherapy.
AB  - Conscious sedation with subanaesthetic doses of propofol is an effective
      technique for the management of highly anxious patients in dentistry. Prolonged
      administration of propofol to achieve conscious sedation in spontaneously
      breathing patients without an airway adjunct has not been reported previously. We
      describe the management of target-controlled conscious sedation with propofol for
      21 h in a patient undergoing gynaecological radiotherapy.

PMID- 8882254
TI  - Lingual nerve paralysis following the use of the laryngeal mask airway.
AB  - A 42-year-old woman, undergoing a diagnostic laparoscopy, developed a unilateral
      lingual nerve palsy following the use of a laryngeal mask airway.

PMID- 8882255
TI  - Intrathecal administration of morphine for elective Caesarean section. A
      comparison between 0.1 mg and 0.2 mg.
AB  - This study compared the quality of analgesia and incidence of adverse effects
      with two doses of intrathecal morphine in patients undergoing elective Caesarean
      section. Fifty patients were randomly allocated to receive either morphine 0.1 mg
      or 0.2 mg in addition to a standard intrathecal dose of 2.5 ml bupivacaine 0.5%
      in 8% dextrose. The quality of analgesia was assessed using visual analogue
      scores and the incidence of nausea, vomiting and itching were recorded during the
      first 24 h postoperatively. There was no statistically significant difference in
      the quality of analgesia nor in the incidence and severity of itching between the
      two groups. Fewer patients in the 0.1 mg morphine group experienced postoperative
      nausea and vomiting (7 versus 14, p < 0.05). We conclude that the use of 0.1 mg
      morphine intrathecally produces comparable analgesia to 0.2 mg after Caesarean
      section with significantly less nausea and vomiting.

PMID- 8882256
TI  - Routine suxamethonium in children. A regional survey of current usage.
AB  - This survey aimed to assess the extent and pattern of use of suxamethonium for
      elective tracheal intubation in children and the occurrence of major
      complications. A postal questionnaire was sent to 280 consultant anaesthetists
      and senior registrars in the West Midlands Region. Of the 180 replies received,
      84% of respondents use suxamethonium routinely. Usage was more common amongst
      those more recently trained (all anaesthetists with less than 10 years experience
      reported using suxamethonium for routine intubation compared with 81% of those
      with over 20 years experience). Reported side effects directly attributable to
      suxamethonium were common, the most frequent being cardiac arrhythmias
      (especially bradycardia) following the first dose (24% respondents) or the second
      dose (43%), and prolonged apnoea (36% of respondents). There were 13 reported
      cardiac arrests (requiring external cardiac massage), three of which were
      associated with repeat dosing and one with undiagnosed Duchenne muscular
      dystrophy. Three cases of documented hyperkalaemia did not lead to cardiac
      arrest. There were two deaths, neither of which could be solely attributed to the
      use of suxamethonium. We conclude that suxamethonium remains popular in
      paediatric practice and that minor side effects are common and usually
      preventable. Life-threatening reactions are rare and until a truly comparable
      alternative is produced this drug will continue to be used in children.

PMID- 8882257
TI  - Injection pain with propofol. Reduction with aspiration of blood.
AB  - A randomised, controlled, single-blind study was performed on 100 patients to
      investigate a new method of reducing pain on propofol injection. Aspiration of 2
      ml of the patient's blood into a syringe of propofol immediately before injection
      was compared with the addition of lignocaine 20 mg or normal saline 2 ml to the
      propofol before injection. The addition of blood was significantly more effective
      in reducing pain on injection than the addition of saline (p < 0.001), but was
      not significantly more effective than the addition of lignocaine.

PMID- 8882258
TI  - Antiemetic efficacy of ondansetron with patient-controlled analgesia.
AB  - A double-blind, randomised, placebo-controlled study was performed to assess the
      antiemetic efficacy of ondansetron in women receiving morphine from a patient
      controlled analgesia system after total abdominal hysterectomy. Sixty-six ASA
      grade 1 or 2 patients scheduled for total abdominal hysterectomy were randomly
      allocated into one of two groups. All patients received a standardised
      anaesthetic and postoperative patient-controlled analgesia regimen. Group 1
      received ondansetron 4 mg at induction of anaesthesia, repeated 8 h later. Group
      2 received saline as a placebo at the same times. Pain scores, nausea scores,
      episodes of vomiting, use of rescue antiemetics and recollection of nausea and
      vomiting were not different between the groups. Only 15% of patients who received
      ondansetron and 30% of patients who received the placebo recorded no nausea or
      vomiting in the first 24 h. We conclude that ondansetron, in the dose studied,
      does not reduce nausea and vomiting in women receiving morphine from a patient
      controlled analgesia system after total abdominal hysterectomy.

PMID- 8882259
TI  - The effect of pretreatment with ketorolac on pain during intravenous injection of
      propofol.
AB  - A randomised, double-blind, controlled trial was undertaken to compare three
      different methods of reducing pain during the intravenous injection of propofol.
      In 101 patients undergoing daycase surgery, verbal rating scores for pain during
      injection of propofol were compared immediately after intravenous pretreatment
      with ketorolac 10 mg, lignocaine 10 mg or saline. Neither pain during injection
      (p = 0.129), nor venous sequelae at 7 days postoperatively were significantly
      different between the three treatments. Pain during propofol injection remains a
      confounding clinical problem.

PMID- 8882260
TI  - Unfamiliar equipment--a cautionary tale.

PMID- 8882261
TI  - Ventilator disconnect alarms.

PMID- 8882262
TI  - Bimanual cricoid pressure.

PMID- 8882263
TI  - Postoperative morbidity following cataract surgery.

PMID- 8882264
TI  - Fluid preload and atrial natriuretic peptide.

PMID- 8882265
TI  - Tachypnoea following vital capacity induction with sevoflurane.

PMID- 8882266
TI  - Intubation and suspected cervical spine injury.

PMID- 8882267
TI  - Pre-operative hypertension; do we postpone surgery too readily?

PMID- 8882268
TI  - Hallucinations after orally administered lorazepam in an adult--a problem
      revisited.

PMID- 8882269
TI  - Repeat dose after an inadequate spinal block.

PMID- 8882270
TI  - Failed spinal anaesthesia.

PMID- 8882271
TI  - Through the needle approach for difficult epidurals.

PMID- 8882272
TI  - The rectus sheath block--well worth remembering.

PMID- 8882273
TI  - Carboxyhaemoglobin-corrected oxygen saturation.

PMID- 8882274
TI  - Use of a fibreoptic intubating laryngoscope to replace a misplaced tracheostomy
      tube.

PMID- 8882275
TI  - Lassoed with a J-wire.

PMID- 8882276
TI  - Tunnelling in the opposite direction.

PMID- 8882278
TI  - Please tell children the truth.

PMID- 8882277
TI  - Patient consent and rectal drug administration.

PMID- 8882279
TI  - Influence of oestrogens on muscarinic receptor density and contractile response
      in the guinea-pig uterus.
AB  - The objective of this study was to investigate the contractile response in vitro
      of uterine and myometrial strips from control and oestrogen-treated guinea-pigs
      to carbachol. In addition, the muscarinic receptor parameters in subcellular
      preparations from the myometrium of the same animals were evaluated. Strips of
      guinea-pig uterus contract in response to carbachol in a concentration dependent
      manner and the effect of carbachol is independent of the presence of an intact
      endometrium. However, treatment with oestrogen reduces the response to carbachol,
      when expressed with respect to the effect of KCl. Measurement of the specific
      binding of [3H]quinuclidinyl benzylate ([3H]QNB) to myometrial membranes from
      control and oestradiol-treated immature guinea-pigs showed that oestradiol
      significantly decreased the number of specific binding sites of [3H]QNB, but did
      not change the apparent affinity of specific [3H]QNB binding. Moreover, the
      apparent affinity constants for the different antagonists showed a close
      similarity to those obtained at muscarinic receptors present in the myometrium
      from control and oestradiol-treated guinea-pigs.

PMID- 8882280
TI  - Immunohistochemical and ultrastructural localization of prostaglandin H synthase
      in the preimplantation mouse embryo.
AB  - The immunohistochemical and ultrastructural localization of prostaglandin H
      synthase (PGH synthase) was studied in the Albino Swiss CF-1 mouse at different
      stages of embryonic development (two-cell stage, four-eight cell stage, morula
      and blastocyst). Flushed embryos and sections of uteri and oviducts containing
      embryos were treated with a mouse IgG monoclonal anti-PGH synthase antibody. The
      second antibody (rabbit anti-mouse) was conjugated with peroxidase or fluorescein
      isothiocyanate for light microscopy, fluorescence microscopy and confocal
      scanning. For reflection contrast microscopy and transmission electron microscopy
      a second antibody, goat anti-mouse, was conjugated with ultrasmall gold
      particles. Controls without anti-PGH synthase were used concurrently. All embryos
      demonstrated PGH synthase reactivity. Immunostaining appeared to be more intense
      at the two-cell stage, four-eight cell stage embryos and morulae than in
      blastocysts. Further examination indicated an intracytoplasmic location for PGH
      synthase, which was confirmed by stereoscopic photographs made during confocal
      scanning microscopy and by the immunostaining patterns observed with reflection
      contrast microscopy and transmission electron microscopy. Transmission electron
      microscopy immunostaining patterns support the localization of PGH synthase in
      the endoplasmic reticulum. This is the first demonstration of the ultrastructural
      localization of PGH synthase in the mouse embryo. Its presence before the
      apposition with the endometrial epithelium supports the hypothesis that
      arachidonic acid metabolism via the PGH synthase pathway may be crucial for
      implantation.

PMID- 8882281
TI  - A preliminary investigation of the relationship between ovarian steroids, LH,
      reproductive behaviour and vaginal changes in lesser bushbabies (Galago moholi).
AB  - Urinary hormone profiles, determined by means of radioimmunoassays, were aligned
      with changes in mating behaviour and vaginal morphology and cytology during the
      ovarian cycles of adult, female lesser bushbabies (Galago moholi), a prosimian
      species. Intromission occurred in all seven females, 2.0 +/- 1.1 days (mean +/-
      SEM, median = 0) after the occurrence of vaginal opening, and lasted for 4.1 +/-
      0.7 days. Three females subsequently gave birth. Vaginal swelling and labial
      reddening were initiated at least 2.5 +/- 0.5 days before vaginal opening and
      lasted 10.4 +/- 0.9 days. Pro-oestrous and vaginal oestrous smears coincided with
      vaginal opening, specifically during the period of mating. Concentrations of
      immunoreactive oestradiol increased during the first few days of vaginal opening
      in one pregnant female and in the nonpregnant females, and coincided with mating.
      Concentrations of immunoreactive progesterone did not show any temporal pattern
      for either pregnant or nonpregnant females. Concentrations of immunoreactive
      testosterone were generally higher during vaginal swelling and opening than
      during the remainder of the cycle in one pregnant female, whereas in nonpregnant
      females, no specific temporal pattern was evident. In both pregnant and
      nonpregnant females, immunoreactive LH concentrations increased during the period
      of vaginal swelling and opening, while in nonpregnant females increases were also
      apparent after vaginal closure. The data reported here are preliminary, and
      further research is necessary to establish conclusively patterns of excreted
      hormones during the reproductive cycles of Galago moholi and in other prosimian
      species.

PMID- 8882282
TI  - Embryo viability, duration of gestation and birth weight in sheep after transfer
      of in vitro matured and in vitro fertilized zygotes cultured in vitro or in vivo.
AB  - The influence of various in vitro procedures on embryo survival and the
      production of normal offspring was investigated in sheep. Zygotes produced from
      in vitro matured (IVM) and fertilized (IVF) oocytes derived from slaughtered
      Merino ewes were allocated to three culture treatments for 6.5 days. Two groups
      were cultured in vitro in the absence or presence of oviduct epithelial cells
      while the third group was cultured in vivo in the oviducts of synchronized ewes.
      A fourth group of zygotes obtained from superovulated Merino ewes was also
      cultured in vivo and served as controls. After culture, IVM-IVF morulae and
      blastocysts, and control embryos were transferred to final recipient ewes.
      Pregnancy was diagnosed at day 50 of gestation by ultrasonography and pregnancies
      were allowed to go to term. The survival to term of IVM-IVF zygotes cultured in
      vitro was reduced compared with both in vivo cultured IVM-IVF zygotes and control
      zygotes (25-35% versus 51-60%, respectively, P < 0.05). Day 6.5 IVM-IVF morulae
      had a lower survival rate than did control morulae regardless of culture
      treatment (P < 0.05), while survival rates of day 6.5 IVM-IVF blastocysts
      cultured in vivo did not differ from those of control blastocysts (P > 0.1). Both
      the gestation period and birth weight of IVM-IVF lambs were increased when
      compared with controls, the former significantly in all groups (154.0-154.9 days
      versus 150.6 days; P < 0.01), while the latter increase was on the borderline of
      significance (4.5-4.8 kg versus 4.0 kg; 0.01 < or = P < or = 0.1, respectively)
      and dependent on the prolongation of the gestation period. It is concluded that
      in vitro maturation and fertilization compromise subsequent embryonic and fetal
      development in sheep irrespective of the subsequent in vivo or in vitro culture
      treatment. Subjecting IVM-IVF zygotes to in vivo culture for 6.5 days minimizes
      only some of these effects, thus leading to the aberrant production of some
      offspring.

PMID- 8882283
TI  - Nutrient partitioning and fetal growth in rapidly growing adolescent ewes.
AB  - A highly controlled model to investigate nutrient partitioning and the control of
      fetal growth in the rapidly growing adolescent sheep is described. Embryos
      recovered from superovulated adult ewes inseminated by a single sire were
      transferred in singleton to the uterus of prepubertal adolescent recipients
      induced to ovulate at 21 weeks of age (liveweight 44.4 +/- 0.38 kg). After embryo
      transfer, the adolescent recipients were individually offered a high (n = 28) or
      low (n = 20) quantity of a complete diet calculated to achieve rapid (RMG) or
      normal (NMG) maternal growth rates. After day 100 of gestation the feed intake of
      the NMG group was adjusted weekly to meet the increasing nutrient demands of the
      gravid uterus. The proportion of adolescent recipients initially conceiving was
      significantly (P < 0.01) influenced by maternal nutrient intake and was lower in
      the RMG (0.57) than in the NMG (0.85) group. For adolescent dams that maintained
      their pregnancies, liveweight gain during the first 95 days of gestation was
      significantly (P < 0.001) higher in the RMG compared with the NMG group (234 +/-
      9.5 and 75 +/- 5.0 g day-1, respectively). Rapid maternal growth rates were
      associated with a significant reduction in both fetal and placental weights as
      determined when the animals were killed on day 95 of gestation (n = 3 per group)
      or at term. For the RMG (n = 8) and NMG (n = 11) groups, respectively, mean lamb
      birthweights at term were 2.74 +/- 0.25 and 4.34 +/- 0.27 kg (P < 0.001), while
      term placental weights were 263 +/- 16.8 and 438 +/- 44.6 g (P < 0.002). The
      number of fetal cotyledons per placenta and mean fetal cotyledon weight were
      significantly lower in RMG compared with NMG ewes (P < 0.05). Irrespective of
      treatment group, lamb birthweight was highly positively correlated with placental
      weight and both parameters were negatively correlated with maternal liveweight
      gain during the first 100 days of gestation. The incidence of non-infectious
      spontaneous abortion at 125 +/- 1.3 days of gestation was higher (P < 0.001) in
      the RMG (4 of 12) than in the NMG (1 of 12) group. Similarly, duration of
      gestation for those ewes delivering live young was shorter (P < 0.01) in the RMG
      compared with the NMG group (140 +/- 0.94 versus 143 +/- 0.28 days). Colostrum
      yield at parturition was positively related to placental weight and significantly
      lower (P < 0.001) in the RMG than in the NMG group (35 +/- 12.1 and 247 +/- 36.2
      g, respectively). Neonatal survival rates at 72 h after parturition were reduced
      (P < 0.05) in the RMG (38%) compared with the NMG group (91%). These data suggest
      that in rapidly growing adolescent ewes, the established anabolic drive to
      maternal tissue synthesis is maintained at the expense of the gradually evolving
      nutrient requirements of the gravid uterus. This results in a major restriction
      in placental growth and a highly significant decrease in birthweight.

PMID- 8882284
TI  - Release of an oxytocic peptide at parturition in the marsupial, Macropus eugenii.
AB  - The oxytocic peptide mesotocin was measured in plasma samples collected
      throughout pregnancy in the conscious tammar wallaby, Macropus eugenii. Plasma
      mesotocin and the prostaglandin metabolite 13,14-dihydro-15-oxo-prostaglandin F2
      alpha were also assessed immediately prepartum and during parturition. A
      radioimmunoassay for mesotocin was validated in the tammar and this assay allowed
      direct measurement in 50 microliters unextracted plasma with a sensitivity of
      12.5 pmol l-1. Plasma concentrations of mesotocin remained basal (approximately
      15 pmol l-1) at all stages of pregnancy, including prepartum. A significant (P <
      0.05) increase in plasma mesotocin was observed only immediately after delivery
      of the neonate and this increase was maintained for at least 15 min postpartum.
      Mesotocin concentrations returned to basal values 2 h after birth. Peak
      concentrations of mesotocin of 516.7 +/- 108.1 pmol l-1 were measured within 2
      min of birth. This peak coincided with a short-lived peak in concentration of
      prostaglandin F2 alpha metabolite immediately after birth (2.1 +/- 0.4 nmol l-1)
      which decreased to less than 0.3 nmol l-1 within 2 h postpartum. These data
      demonstrate that mesotocin is released during, or immediately after, delivery and
      appears to parallel the profile of circulating prostaglandin F2 alpha metabolite
      in this marsupial.

PMID- 8882285
TI  - Regulation of epidermal growth factor receptor synthesis by ovarian steroids in
      human endometrial cells in culture.
AB  - The aim of this study was to investigate the effect of oestradiol and
      progesterone on epidermal growth factor (EGF) binding in human endometrial glands
      and stromal cells in culture. Monolayers of isolated glands or stromal cells were
      cultured for 6 days in the presence or absence of steroids which were replenished
      daily. Binding of 125I-labelled EGF was measured in the presence and absence of
      unlabelled EGF. Over a 6 day period, oestradiol caused a dose-dependent increase
      in the number of EGF receptors in stromal cells, with a maximum effect of 150%
      control at a concentration of 10 nmol l-1. The effect of progesterone was also
      dose dependent and reached a maximum of 170% control at 100 nmol progesterone l
      1. Oestradiol and progesterone in combination caused a greater increase in EGF
      receptor concentration than did either steroid alone (control, 100 +/- 11%;
      oestradiol, 144 +/- 11% control; progesterone, 200 +/- 20% control; oestradiol
      and progesterone, 288 +/- 6% control). Steroid treatment did not alter the
      affinity of the receptor for EGF. The stage of the cycle of the tissue did not
      affect the response to steroids. The effect of oestradiol was inhibited by the
      anti-oestrogen ICI182780, and that of progesterone by the anti-progestin RU486.
      In endometrial glands, neither oestradiol nor progesterone affected the number of
      EGF receptors, but the two steroids in combination induced an increase of 140 +/-
      23% control where control was 100 +/- 15%. These data demonstrate that oestradiol
      and progesterone increase the number of EGF receptors in vitro, and suggest that
      EGF is involved in mediating the actions of these steroids on the processes of
      proliferation and differentiation in the human endometrium.

PMID- 8882286
TI  - Role of antral follicle development and cumulus cells on in vitro fertilization
      of mouse oocytes.
AB  - The role exerted by antral follicle development and by companion granulosa cells
      on the ability of mouse oocytes at metaphase II to fuse with spermatozoa (as
      estimated by the kinetics of sperm-egg fusion), and to support normal
      fertilization (estimated by the formation of a male pronucleus) was investigated.
      After 17 h of culture in vitro, nuclear maturation occurred in 82% of oocytes
      derived from early antral follicles devoid of granulosa cells (denuded oocytes)
      and in 95% of oocytes derived from preovulatory follicles and cultured cumulus
      intact or cumulus-free. Among the matured oocytes, 95% of cumulus-intact oocytes
      were arrested at metaphase II, while 61% of denuded and 50% of cumulus-free
      oocytes were arrested at metaphase I. The competence of denuded and cumulus-free
      oocytes to override the metaphase I stage was not affected by the addition of
      preantral granulosa, early antral granulosa or cumulus cells to the maturation
      medium. The kinetics of sperm-oocyte fusion were comparable in cumulus-intact and
      cumulus-free oocytes, and were more rapid than those of the early antral oocytes
      for insemination periods up to 60 min. However, when denuded oocytes were matured
      in medium containing early antral granulosa or cumulus cells, the kinetics of
      sperm-egg fusion was greatly accelerated to values equivalent to those of
      preovulatory oocytes. The ability of denuded oocytes to fuse with spermatozoa was
      unaffected by the addition of preantral granulosa cells to the maturation medium.
      Sixty minutes after insemination, the fertilization rates were 39% for denuded
      oocytes, 50% for cumulus-free oocytes and 73% for cumulus-intact oocytes. The
      fertilization rate of denuded and cumulus-free oocytes was significantly improved
      by the addition to the maturation medium of cumulus cells, but not by the
      addition of preantral or early antral granulosa cells. Taken together, the
      present results show that in mice, the maturation of both oolemma and ooplasm,
      required for successful fertilization, is acquired together with the development
      of antral follicles and is positively affected by cumulus cells during meiotic
      progression.

PMID- 8882287
TI  - Effect of cycloheximide on nuclear maturation of horse oocytes and its relation
      to initial cumulus morphology.
AB  - The period of protein synthesis necessary for meiotic maturation in horse oocytes
      initially having compact or expanded cumulus cells was studied. Oocytes incubated
      in the presence of cycloheximide after 0, 4, 8, 12 or 16 h maturation in vitro
      (total incubation time 24 h) were matured for 24 h, or were incubated with
      cycloheximide for 24 h and then matured for 24 h. Incubation with cycloheximide
      from 0 h was effective in suppressing maturation (no significant increase in
      maturing oocytes compared with controls fixed directly after removal from the
      follicle) in both expanded and compact groups and was completely reversible, as
      there was no difference in the proportion of oocytes reaching metaphase II
      between controls and treatment groups of either cumulus type. Addition of
      cycloheximide after 4 h maturation resulted in no significant difference in
      distribution of oocytes compared with addition at 0 h in either cumulus group. A
      significant decrease in the proportion of germinal vesicle stage oocytes, and an
      increase in oocytes in metaphase I occurred in oocytes with expanded cumulus
      cells in the 8 h treatment and in oocytes with compact cumulus cells in the 12 h
      treatment, compared with oocytes treated after 0 h. A significant increase in the
      proportion of oocytes at metaphase II occurred in the 12 h treatment for expanded
      cumulus-oocyte complexes and in the 16 h treatment for compact cumulus-oocyte
      complexes. These data show that nuclear maturation of horse oocytes can be
      reversibly suppressed by incubation with cycloheximide from the onset of culture.
      Oocytes with different initial cumulus type differed in the time required for
      protein synthesis essential for maturation: expanded cumulus-oocyte complexes
      required less time to prepare for germinal vesicle breakdown, maturation to
      metaphase I, and maturation to metaphase II, than did compact cumulus-oocyte
      complexes.

PMID- 8882288
TI  - Effects of insulin-like growth factors and binding protein 1 on bovine granulosa
      cell division in anchorage-independent culture.
AB  - Granulosa cells can exhibit the properties of stem cells and tumour cells.
      Contact with neighbouring cells does not inhibit their replication in vivo and
      they can divide in vitro while embedded in agar and thus without anchorage on a
      substratum. By culturing granulosa cells without anchorage, those cells that do
      not require anchorage, and thus exhibit at least one property of stem cells,
      divide. The effects of insulin-like growth factors (IGFs) and insulin-like growth
      factor binding protein 1 (IGFBP-1) on the replication of such cells was
      investigated by isolating granulosa cells from follicles (3-5 mm diameter) from
      cyclic cows and culturing them in soft agar-methylcellulose solution. Cell
      division was measured as [3H]thymidine incorporation into DNA, total DNA, or as
      the amount of the nuclear La antigen. This antigen is involved in RNA synthesis
      and is expressed ubiquitously; here it was used to estimate the number of cells
      indirectly. Both IGF-I (100 ng ml-1) and IGF-II (100 ng ml-1) and their
      respective analogues, as well as insulin, all at the same concentration,
      significantly increased DNA synthesis as determined by [3H]thymidine
      incorporation (n = 5). An increase in the number of cells in the presence of IGF
      I was also confirmed by DNA measurement (P < 0.05, n = 5) and by western
      immunoblotting analyses of La antigen (n = 3). IGFBP-1 significantly inhibited
      cell division stimulated by IGF-I (P < 0.001) and IGF-II (P < 0.001), but not
      that stimulated by the analogue, LR3IGF-I, which has low affinity for IGFBPs.
      Other factors also known to affect IGF synthesis or effectiveness (FSH,
      oestradiol, growth hormone) did not appear to influence division of granulosa
      cells when cultured under anchorage-independent conditions, while dibutyryl cAMP
      significantly inhibited cell division (P < 0.01, n = 5). In conclusion, IGFs have
      a role to play in stimulating division of stem-cell-like granulosa cells during
      follicular development and IGFBP-1 can specifically inhibit the mitogenic effects
      of IGFs.

PMID- 8882289
TI  - Protein content of cattle oocytes and embryos from the two-cell to the elongated
      blastocyst stage at day 16.
AB  - The protein content of cattle oocytes and preimplantation embryos produced in
      vivo, from the two-cell to the elongated blastocyst at day 16, was determined.
      From the oocyte to the expanded blastocyst stage (day 8), protein determination
      was carried out on zona pellucida-enclosed embryos. Protein content was measured
      by the Pierce Micro BCA protein assay. The mean protein content of oocytes was
      0.126 micrograms, with no significant increase at the two-cell stage (0.132
      micrograms). Protein content was higher at the morula stage (0.183 micrograms; P
      < 0.05) with a further increase at the expanded blastocyst stage (0.367
      micrograms; P < 0.05). There was a 160-fold increase in protein content from the
      expanded blastocyst to the hatched day 13 stage. Spherical, ovoid and elongated
      blastocysts were collected on days 13 and 14. The mean protein content of day 13
      (59.8 micrograms) and day 14 (92.4 micrograms) embryos was similar (P > 0.1), but
      the protein content of the elongated embryos was higher than that of ovoid or
      spherical embryos collected on the same day. Protein content of day 15 embryos
      (362.2 micrograms) was higher than that on day 14, with a further increase to
      946.6 micrograms by day 16. The correlation between protein content and day of
      development contained both a linear and a quadratic component. Embryo length and
      width increased from day 13 (5.24 mm and 0.89 mm, respectively) to day 16 (51.6
      mm and 1.82 mm, respectively). From day 13 to day 16, the protein content was
      correlated with both embryo length and width (r2 = 0.89 and 0.51, respectively; P
      < 0.001) and was highly correlated (r2 = 0.95) with the product of embryo length
      by width, indicating that protein content increases as a function of surface
      area.

PMID- 8882290
TI  - Suppression of matrix metalloproteinase production by hCG in cultures of human
      luteinized granulosa cells as a model for gonadotrophin-induced luteal rescue.
AB  - Granulosa cells were isolated from follicular aspirates collected at ovum
      recovery for in vitro fertilization. Cells were cultured in a defined medium on
      artificial extracellular matrix (Matrigel) in the presence or absence of hCG as a
      model for corpus luteum function. Release of cells from this culture system is
      reduced by hCG and this effect may be mediated through an inhibition of
      extracellular matrix degradation. Using zymography and western blot analysis, we
      confirm the identity of matrix metalloproteinases-2 and -9 in culture media.
      Matrix metalloproteinase-9 was the predominant gelatinase in freshly prepared
      granulosa cells and in culture media, and also represented a major
      metalloproteinase component in homogenates of early and mid-luteal phase samples
      of corpora lutea. Quantitative analysis of matrix metalloproteinases in culture
      media, obtained throughout the 14 day culture period and expressed per microgram
      of DNA, showed that matrix metalloproteinase-2, undetectable on day 2, rose
      throughout the culture period and that this rise was significantly inhibited by
      hCG. In contrast, matrix metalloproteinase-9 was clearly detectable on day 2 and
      remained relatively constant throughout much of the culture (day 2 to day 12) in
      the presence of gonadotrophin. Significantly increased production of matrix
      metalloproteinase-9 (day 6 to day 12) was evident in the absence of hCG. Our
      results provide further evidence for the hypothesis that the rescue of the corpus
      luteum in early pregnancy involves the maintenance of cellular function through
      the stabilization of the extracellular matrix.

PMID- 8882291
TI  - Differential effect of trilostane on the progestin milieu in the pregnant mare.
AB  - Trilostane, a competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase, was
      administered intravenously to pregnant mares (n = 3) between day 277 and day 282
      of gestation to determine its effect on the progestin milieu. In addition,
      placental tissue from mares at mid-gestation (150-300 days) (n = 4) were exposed
      to either deuterium-labelled pregnenolone alone or deuterium-labelled
      pregnenolone and trilostane to examine the effect of trilostane on placental
      metabolism of pregnenolone. Blood samples were collected from indwelling jugular
      catheters at frequent intervals for 48 h after infusion. Both plasma samples and
      incubation media were quantitatively analysed, after solid phase extraction and
      steroid derivitization, for concentrations of eight different progestin
      metabolites using gas chromatography and mass spectrometry. Trilostane infusion
      differentially affected the progestin milieu in vivo without inducing abortion.
      Forty-five minutes after infusion, maternal plasma concentrations of
      pregnenolone, 5-pregnene-3 beta, 20 beta-diol, 5 alpha-pregnane-3 beta,20 beta
      diol and 3 beta-hydroxy-5 alpha-pregnan-20-one increased (P < 0.05) and remained
      high for 37 h. Concentrations of 5 alpha-pregnane-3,20-dione, 20 alpha-hydroxy-5
      alpha-pregnan-3-one and 5 alpha-pregnane-3 beta,20 alpha-diol decreased 15 min
      after infusion (P < 0.05), yet 1.5 h after infusion, concentrations had increased
      and remained high until 37 h after infusion. Trilostane inhibited the conversion
      of pregnenolone to progesterone in vitro (P < 0.001) while mediating an increase
      (P < 0.05) in concentrations of 5 alpha-pregnane-3,20-dione and 3 beta-hydroxy-5
      alpha-pregnan-20-one. These observations demonstrate that the pregnant mare
      possesses unique steroid hormone metabolic activity and suggests that another
      steroid, perhaps 5 alpha-pregnane-3,20-dione and not progesterone, is the
      important steroid precursor for the other progestin metabolites found in
      circulating plasma.

PMID- 8882292
TI  - Nitric oxide synthase isoforms in the rat uterus: differential regulation during
      pregnancy and labour.
AB  - Production of nitric oxide in the uterus is increased during pregnancy and
      decreased during delivery. In this study the isoform of nitric oxide synthase
      which may be responsible for the changes in nitric oxide production was
      investigated in relation to pregnancy and delivery. Monoclonal antibodies were
      used to measure changes in neuronal nitric oxide synthase (NOS I), macrophage
      nitric oxide synthase (NOS II) and endothelial cell nitric oxide synthase (NOS
      III) protein in the rat uterus by densitometric scanning of specific bands.
      Results show that: (1) NOS II protein concentrations in the uterus were
      substantially increased during pregnancy and were decreased during delivery, both
      at term and preterm (induced by RU486); (2) NOS III protein was present at all
      stages examined but the concentrations were unchanged; (3) NOS I was present in
      the rat uterus during the nonpregnant stage but not during pregnancy and
      delivery. The changes in uterine NOS II protein concentrations during pregnancy
      and delivery were further confirmed by the changes in the Ca(2+)-independent, but
      not Ca(2+)-dependent, nitric oxide synthase activity. Therefore, an increase in
      NOS II, thus in nitric oxide production during pregnancy, may play a role in
      maintaining uterine quiescence.

PMID- 8882293
TI  - Colocalization of connexin 43 and connexin 45 but absence of connexin 40 in
      granulosa cell gap junctions of rat ovary.
AB  - The expression and localization of gap junction family proteins (connexins) were
      examined in nonstimulated and gonadotrophin-stimulated ovarian follicles of
      immature rats. Immunoblot and RNA blot analysis showed the presence of connexin
      (Cx) 43, Cx40 and Cx45 in ovarian tissue. Of these connexin proteins, Cx43 and
      Cx45 were identified by immunofluorescent microscopy between granulosa cells in
      characteristic expression patterns related to follicular developmental stages,
      while Cx40 was not expressed in granulosa cells but was detected in blood vessels
      in ovarian stroma. In some plaques of gap junction between granulosa cells, Cx45
      was found to be colocalized with Cx43. In immunofluorescent microscopy, the
      expression of Cx43 was increased with follicular growth, but decreased after
      induction of ovulation by injection of human chorionic gonadotrophin. In
      contrast, the Cx45 protein was constantly expressed through follicular
      development; however, after ovulation, no staining of Cx45 was detected in the
      corpus luteum. Dual expression and the functional role of Cx43 and Cx45 in cell
      to-cell communication in ovarian granulosa cells at various developmental stages
      were discussed.

PMID- 8882294
TI  - Role of high molecular weight seminal vesicle proteins in eliciting the uterine
      inflammatory response to semen in mice.
AB  - Mating evokes a characteristic pattern of molecular and cellular events in the
      rodent reproductive tract, including an infiltration of the endometrial stroma
      and uterine lumen with activated macrophages and granulocytes, which closely
      resembles a classic inflammatory response. Previous studies in mice indicate that
      these cellular changes are associated with, and are largely a consequence of, an
      upregulated synthesis and release of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) from the uterine epithelium in response to seminal fluid. The aim
      of this study was to investigate further the origin and nature of the factors
      present in seminal fluid that trigger the GM-CSF response. It was found that the
      characteristic increase in uterine expression of mRNA encoding GM-CSF and release
      of GM-CSF bioactivity from uterine epithelial cells into the luminal cavity seen
      after mating with intact or vasectomized males was no longer evident in matings
      with male mice from whom the seminal vesicles had been surgically removed. The
      extent of inflammatory leucocyte infiltration into the endometrium was also
      reduced; the most notable effect was a complete absence of the exocytosis of
      neutrophils into the luminal cavity normally seen after matings with intact or
      vasectomized males. Bioassay of the GM-CSF output of oestrous endometrial cells
      after culture with crude or Sephacryl S-400 chromatographed fractions of seminal
      vesicle fluid showed that the GM-CSF stimulating activity was predominantly
      associated with protein moieties in seminal vesicle fluid of approximately
      650,000 M(r) and 100,000-400,000 M(r). These data confirm the presence in seminal
      vesicle fluid of specific factors that initiate an inflammatory response in the
      uterus after mating through upregulating GM-CSF synthesis in the uterine
      epithelium. The significance of the cytokine release and cellular changes induced
      by seminal plasma for implantation of the conceptus and pregnancy outcome remain
      to be determined.

PMID- 8882295
TI  - Mouse fetal antigen 1 (mFA1), the circulating gene product of mdlk, pref-1 and
      SCP-1: isolation, characterization and biology.
AB  - The mouse homologue to human fetal antigen 1 (hFA1) was purified from mouse
      amniotic fluid by cation exchange chromatography and immunospecific affinity
      chromatography. Mouse FA1 (mFA1) is a single chain glycoprotein with an M(r) of
      42-50 kDa (SDS-PAGE). The N-terminal amino acid sequence (39 residues) revealed
      74% identity to hFA1 and 100% identity to the translated cDNAs referred to as
      mouse dlk, pref-1 and SCP-1. mFA1 is the secreted processed molecule encoded by
      the mRNA defined by these identical mouse cDNAs. Monospecific rabbit anti-mFA1
      antibodies, purified by ammonium sulfate precipitation and immunospecific
      affinity chromatography, were used for immunohistochemical and quantitative ELISA
      techniques. The indirect immunoperoxidase technique demonstrated mFA1 within the
      endocrine structures of adult mouse pancreas, whereas the exocrine tissue
      remained unstained. FA1-positive staining was also seen in the pituitary gland
      and the mouse adrenal gland. The concentration of mFA1 in a pool of amniotic
      fluid was assessed at 25 micrograms ml-1 and the serum concentration in normal
      nonpregnant adult mice (n = 28) was 11.3 +/- 5.0 ng ml-1 (2 SD). During pregnancy
      the concentration of mFA1 in maternal serum increased above the nonpregnant
      reference value at midpregnancy, reaching a maximum concentration (> 0.35
      microgram ml-1) 2 days prepartum. The maternal serum concentration was positively
      correlated with the number of fetuses. After delivery the rate of disappearance
      of mFA1 in maternal serum was very fast with a t1/2 < 1 h. The concentration of
      mFA1 in newborn mice was about 15 micrograms ml-1 and did not reach normal adult
      values until the age of > 50 days.

PMID- 8882297
TI  - Effects of oxytocin on sperm transport in the pubertal rat.
AB  - Oxytocin is present in the mammalian testis where it increases contractility of
      seminiferous tubules in vitro and has been implicated in sperm transport. The
      present study investigated whether oxytocin affects the transport of spermatozoa
      from the testis in vivo. In rats, mature spermatozoa are first seen in the testis
      42 days postpartum and arrive in the epididymis at about day 45. Male Wistar rats
      were given daily subcutaneous injections of either oxytocin (0.5 micrograms), the
      oxytocin antagonist des Gly-NH2d(CH2)5-[D-Tyr2,Thr4]OVT (0.2 micrograms) or
      saline from day 40 postpartum. Groups of six animals were killed 2 h after their
      last injection on days 43, 44, 45 and 46 postpartum. Testes were removed and
      fixed in Bouin's fluid for histological examination and the number of spermatozoa
      in the epididymides was counted. Spermatozoa were seen in the epididymis earlier
      in the oxytocin-treated rats (day 43) than in the control animals (day 44), and
      treatment with the antagonist delayed the appearance of spermatozoa in the
      epididymis until day 45. When the testes were examined, residual bodies, which
      were used as an indicator of spermiation, were seen only in one control animal
      before day 44. Residual bodies were seen in the testes of all oxytocin-treated
      rats on day 43 but were not detected until day 45 in the oxytocin antagonist
      treated rats. These data show that in rats oxytocin can affect the arrival of
      spermatozoa in the epididymis. Although this may be due in part to effects on
      tubal transport or the secretion of tubular fluid, these findings suggest that
      the peptide may affect spermiation.

PMID- 8882296
TI  - Inhibition of bovine fertilization in vitro by antibodies to SP-10.
AB  - The inhibiting effect on fertilization of antibodies to the intra-acrosomal
      protein SP-10 was studied in a bovine in vitro fertilization model. Indirect
      immunofluorescence showed that antibodies to human SP-10 localized to the
      acrosomal region of methanol-fixed, but not live, bovine spermatozoa, confirming
      the intra-acrosomal localization of bovine SP-10. The presence of the SP-10
      protein in bovine spermatozoa was further established by immunoblotting of
      extracts of bovine spermatozoa with monoclonal antibodies and polyclonal
      antibodies to human SP-10. The antibodies identified a pattern of immunoreactive
      peptides similar to human, baboon, monkey and pig SP-10. Fertilization
      experiments in vitro demonstrated that monoclonal antibodies, as well as
      polyclonal antibodies, to human SP-10 significantly reduced fertilization rates
      of bovine oocytes by bovine spermatozoa. SP-10 antibodies exerted their anti
      fertilization effect by reducing sperm-zona secondary binding. Consistent with
      the accessibility of the SP-10 antigen following capacitation, SP-10 antibodies
      also reduced the ability of capacitated spermatozoa to complete the acrosome
      reaction. Furthermore, SP-10 antibodies affected the motility of capacitated
      spermatozoa, while not affecting the motility of noncapacitated spermatozoa.

PMID- 8882298
TI  - Role of receptors for epidermal growth factor and insulin-like growth factors I
      and II in the differentiation of rat mammary glands from lactogenesis I to
      lactogenesis II.
AB  - In addition to ovarian steroids and lactogenic hormones from the placenta and
      pituitary, growth factors control the growth and differentiation of mammary
      glands. Lactogenesis II at the end of pregnancy is under the control of
      progesterone. Ovariectomy results in a significant decrease in the number of
      receptors for epidermal growth factor (EGF) and insulin-like growth factor I (IGF
      I) and an increase in IGF-II binding sites in mammary gland acini of rats,
      without affecting the affinity for their respective ligand. Although
      concentrations of EGF, IGF-I and IGF-II receptors are regulated by oestradiol and
      progesterone, replacement treatment with ovarian steroids after ovariectomy
      showed that receptor concentrations do not mediate the restraint on lactogenesis.
      Progesterone treatment, which inhibits the onset of lactogenesis II, did not
      restore EGF receptor concentrations to control values, and the presence of
      oestradiol was required to reverse the effect of ovariectomy. Oestradiol, which
      potentiates the effect of ovariectomy on milk synthesis, increases IGF-I receptor
      concentrations. IGF-II receptor concentrations, after the different steroid
      treatments, were consistent with the steroid effect on milk synthesis. The
      changes observed in the concentrations of these growth factor receptors at the
      onset of mammary gland secretion are not considered to affect the progesterone
      block to lactogenesis II, but rather are a consequence of the shift of the
      hormonal and, hence, physiological status of the gland.

PMID- 8882299
TI  - Transplantation of cryopreserved fetal ovarian tissue to adult recipients in
      mice.
AB  - Sixteen-day-old fetal mouse ovaries were slowly frozen in 1.5 mol
      dimethylsulfoxide ml-1 and subjected to one of two thawing procedures--fast thaw
      or slow thaw. Fresh and frozen-thawed fetal ovaries were transplanted
      orthotopically (to the bursal cavity) to either bilaterally or unilaterally
      ovariectomized adult female recipients. Fresh fetal ovaries were also
      transplanted heterotopically (under the kidney capsule) to intact, bilaterally or
      unilaterally ovariectomized adult females. Transplantation of fetal ovaries to
      bilaterally ovariectomized adult recipients resulted in restoration of cyclic
      activity within 20.5 +/- 4.7 (mean +/- SEM) days or 23.4 +/- 0.8 days in
      orthotopic and heterotopic groups, respectively. Developing follicles and corpora
      lutea were observed within 4 weeks after transplantation of fetal ovaries to
      heterotopic sites and within 6 weeks after transplantation to orthotopic sites.
      After orthotopic transplantation, 33% of the recipients became pregnant.
      Orthotopic or heterotopic transplantation to intact of unilaterally
      ovariectomized recipients resulted in quiescence of the fetal ovary. After
      cryopreservation, transplantation of fetal ovaries to bilaterally ovariectomized
      recipients resulted in restoration of cyclic activity within 19.3 +/- 2.1 days
      and 23.4 +/- 5.1 days after transplantation in slow thaw and fast thaw groups,
      respectively. Fertility was restored to 86% of fast thawed and 25% of slow thawed
      fetal ovary transplants to bilaterally ovariectomized adult recipients. No
      ovarian tissue was observed on the side of the fetal graft in unilaterally
      ovariectomized recipients that received frozen-thawed fetal ovaries. These
      results demonstrate that cryopreserved fetal ovarian tissue can be transplanted
      to adult recipients with subsequent restoration of fertility and that this
      process is dependent on the absence of the ovaries of the recipients.

PMID- 8882300
TI  - A new microemulsion formulation of cyclosporin: pharmacokinetic and clinical
      features.
AB  - Cyclosporin (cyclosporin A) has been used as an immunosuppressive agent after
      organ transplantation for more than 15 years. The bioavailability of cyclosporin
      in its conventional oral formulation 'Sandimmun' displays considerable inter- and
      intra-patient variability. Absorption is also bile dependent. Recently, a new
      galenic formulation of cyclosporin was introduced, 'Neoral', which is a water
      free microemulsion of cyclosporin. The microemulsion creates micelles which are
      absorbed in the small bowel without the presence of bile. Pharmacokinetic studies
      in healthy volunteers clearly demonstrate an increased bioavailability of the
      microemulsion formulation of cyclosporin, measured as an increase in maximum drug
      concentration (Cmax) and area under the drug concentration-time curve, and a
      reduced time to Cmax. These findings have been confirmed in kidney, liver and
      heart transplant recipients. With the microemulsion formulation, an improved
      prediction of cyclosporin concentrations has probably attributed to the decrease
      found in the variability of cyclosporin absorption. This could probably enable
      easier and more reliable monitoring of cyclosporin concentrations after
      transplantation. So far, data on the effects of conversion from the conventional
      to the microemulsion formulation of cyclosporin are only available in a limited
      number of patients and with a limited follow-up period. The main questions are
      related to what the long term consequences of the improved bioavailability of the
      microemulsion formulation will be. Further long term studies are needed in order
      to answer these questions. In the present review, we report on the
      pharmacokinetic properties of, and on clinical experience after solid organ and
      bone marrow transplantation with, the microemulsion formulation.

PMID- 8882301
TI  - Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis.
AB  - Low-dose pulse methotrexate has emerged as one of the most frequently used slow
      acting, symptom-modifying antirheumatic drugs in patients with rheumatoid
      arthritis (RA) because of its favourable risk-benefit profile. Methotrexate is a
      weak bicarboxylic acid structurally related to folic acid. The most widely used
      methods for the analysis of methotrexate are immunoassays, particularly
      fluorescence polarisation immunoassay. After oral administration, the drug is
      rapidly but incompletely absorbed. Since food does not significantly affect the
      bioavailability of oral methotrexate in adult patients, the drug may be taken
      regardless of meals. There is a marked interindividual variability in the extent
      of absorption of oral methotrexate. Conversely, the intraindividual variability
      is moderate even over a long time period. Intramuscular and subcutaneous
      injections of methotrexate result in comparable pharmacokinetics, suggesting that
      these routes of administration are interchangeable. A mean protein binding to
      serum albumin of 42 to 57% is usually reported. Again, the unbound fraction
      exhibits a large interindividual variability. The steady-state volume of
      distribution is approximately 1 L/kg. Methotrexate distributes to extravascular
      compartments, including synovial fluid, and to different tissues, especially
      kidney, liver and joint tissues. Finally, the drug is transported into cells,
      mainly by a carrier-mediated active transport process. Methotrexate is partly
      oxidised by hepatic aldehyde oxidase to 7-hydroxymethotrexate. This main,
      circulating metabolite is over 90% bound to serum albumin. Both methotrexate and
      7-hydroxy-methotrexate may be converted to polyglutamyl derivatives which are
      selectively retained in cells. Methotrexate is mainly excreted by the kidney as
      intact drug regardless of the route of administration. The drug is filtered by
      the glomeruli, and then undergoes both secretion and reabsorption processes
      within the tubule. These processes are differentially saturable, resulting in
      possible nonlinear elimination pharmacokinetics. The usually reported mean values
      for the elimination half-life and the total body clearance of methotrexate are 5
      to 8 hours and 4.8 to 7.8 L/h, respectively. A positive correlation between
      methotrexate clearance and creatinine clearance has been found by some authors.
      Finally, the pharmacokinetics of low-dose methotrexate appears to be highly
      variable and largely unpredictable even in patients with normal renal and hepatic
      function. Furthermore, studies in patients with juvenile rheumatoid arthritis
      provide evidence of age-dependent pharmacokinetics of the drug. These features
      must be considered when judging the individual clinical response to methotrexate
      therapy. Various drugs currently used in RA may interact with methotrexate.
      Aspirin might affect methotrexate disposition to a greater extent than other
      nonsteroidal anti-inflammatory drugs without causing greater toxicity.
      Corticosteroids do not interfere with the pharmacokinetics of methotrexate,
      whereas chloroquine may reduce the gastrointestinal absorption of the drug.
      Folates, especially folic acid, have been shown to reduce the adverse effects of
      methotrexate without compromising its efficacy in RA. Finally, both trimethoprim
      sulfamethoxazole (cotrimoxazole) and probenecid lead to increased toxicity of
      methotrexate, and hence should be avoided in patients receiving these drugs. A
      relationship between oral dosage and efficacy has been found in the range 5 to
      20mg methotrexate weekly. The plateau of efficacy is attained at approximately 10
      mg/m2/week in most patients. No clear relationship between pharmacokinetic
      parameters and clinical response has been demonstrated. Overall, the dosage must
      be individualised because of interindividual variability in the dose-response
      curve. This variability is probably related, at least in part, to the wide
      interindividual variability in the disposition of the drug.

PMID- 8882304
TI  - Molecular mechanisms of iron transport.
AB  - The homeostasis of iron transport and absorption represents a critical mechanism
      to maintain the necessary physiologic balance of this essential nutrient. Recent
      advances in our understanding of the molecular mechanisms involved in the
      transport of iron and its membrane translocation are reviewed. Translational and
      transcriptional control mechanisms that have been characterized to play a role in
      iron homeostasis are also discussed.

PMID- 8882305
TI  - The regulation and regulatory role of collagenase in bone.
AB  - Interstitial collagenase plays an important role in both the normal and
      pathological remodeling of collagenous extracellular matrices, including skeletal
      tissues. The enzyme is a member of the family of matrix metalloproteinases. Only
      one rodent interstitial collagenase has been found but there are two human
      enzymes, human collagenase-1 and -3, the latter being the homologue of the rat
      enzyme. In developing rat and mouse bone, collagenase is expressed by
      hypertrophic chondrocytes, osteoblasts, and osteocytes, a situation that is
      replicated in a fracture callus. Cultured osteoblasts derived from neonatal rat
      calvariae show greater amounts of collagenase transcripts late in
      differentiation. These levels can be regulated by parathyroid hormone (PTH),
      retinoic acid, and insulin-like growth factors, as well as the degree of matrix
      mineralization. Much of the work on collagenase in bone has been derived from
      studies on the rat osteosarcoma cell line, UMR 106-01. All bone-resorbing agents
      stimulate these cells to produce collagenase mRNA and protein, with PTH being the
      most potent stimulator. Determination of secreted levels of collagenase has been
      difficult because UMR cells, normal rat osteoblasts, and rat fibroblasts possess
      a scavenger receptor that removes the enzyme from the extracellular space,
      internalizes and degrades it, thus imposing another level of control. PTH can
      also regulate the abundance of the receptor as well as the expression and
      synthesis of the enzyme. Regulation of the collagenase gene by PTH appears to
      involve the cAMP pathway as well as a primary response gene, possibly Fos, which
      then contributes to induction of the collagenase gene. The rat collagenase gene
      contains an activator protein-1 sequence that is necessary for basal expression,
      but other promoter regions may also participate in PTH regulation. Thus, there
      are many levels of regulation of collagenase in bone perhaps constraining what
      would otherwise be a rampant enzyme.

PMID- 8882303
TI  - Diuretic combinations in refractory oedema states: pharmacokinetic
      pharmacodynamic relationships.
AB  - Diuretic resistance is encountered in a number of disease states, such as chronic
      renal failure, nephrotic syndrome, congestive heart failure (CHF) and cirrhosis.
      Diuretic stratagems which produce sequential nephron segment blockade, and thus a
      synergistic diuretic response, are frequently necessary and are regularly
      employed in these conditions. Pharmacokinetic determinants of diuretic response,
      including dose administered, absolute bioavailability, and tubular transport
      capacity and transport rate, are reviewed here. Pharmacodynamic factors are
      perhaps more important to overall response, and often result in modification of
      the dose-response relationship; these are also reviewed here. Stratagems used to
      maximise the diuretic response to loop diuretics include correcting abnormal
      haemodynamic parameters, utilising larger doses or constant intravenous
      infusions, and using albumin as a vehicle to deliver the loop diuretic to the
      site of tubular secretion. If these measures fail, then diuretic combinations are
      useful. Perhaps the most effective is the combination of metolazone (a thiazide
      type diuretic) and a loop diuretic. The rationale for and use of various diuretic
      combinations, with particular emphasis on the metolazone-loop diuretic
      combination, is reviewed here and applied to the major disease states associated
      with diuretic resistance.

PMID- 8882302
TI  - Drug monitoring in nonconventional biological fluids and matrices.
AB  - Determination of the concentration of drugs and metabolites in biological fluids
      or matrices other than blood or urine (most commonly used in laboratory testing)
      may be of interest in certain areas of drug concentration monitoring. Saliva is
      the only fluid which can be used successfully as a substitute for blood in
      therapeutic drug monitoring, while an individual's past history of medication,
      compliance and drug abuse, can be obtained from drug analysis of the hair or
      nails. Drug concentrations in the bile and faeces can account for excretion of
      drugs and metabolites other than by the renal route. Furthermore, it is important
      that certain matrices (tears, nails, cerebrospinal fluid, bronchial secretions,
      peritoneal fluid and interstitial fluid) are analysed, as these may reveal the
      presence of a drug at the site of action; others (fetal blood, amniotic fluid and
      breast milk) are useful for determining fetal and perinatal exposure to drugs.
      Finally, drug monitoring in fluids such as cervical mucus and seminal fluid can
      be associated with morpho-physiological modifications and genotoxic effects. Drug
      concentration measurement in nonconventional matrices and fluids, although
      sometimes expensive and difficult to carry out, should therefore be considered
      for inclusion in studies of the pharmacokinetics and pharmacodynamics of new
      drugs.

PMID- 8882306
TI  - Gene therapy: basic concepts and recent advances.
AB  - After years of preliminary in vitro and in vivo modeling, the first human gene
      therapy clinical trial was initiated approximately 5 years ago. The experience
      gained from this trial, and the others that have come after it, has shown that
      effective and efficient human gene therapy remains a tantalizing but elusive
      goal. Nevertheless, interest in this area of therapeutics continues to grow and
      over 100 gene therapy protocols have now been submitted to the Recombinant DNA
      Advisory Committee ("RAC") of the National Institutes of Health for approval. The
      goal of these protocols vary, but include correction of inherited gene defects,
      engineering new traits into cells such as diminished chemosensitivity in the case
      of bone marrow cells, or, in the case of tumor cells, expression of new
      immunophenotypes. Marking cells with a gene whose function can easily be
      detected, thereby rendering the cell traceable in vitro and in vivo is also the
      goal of several clinical trials. At the same time, different means of gene
      transfer are been investigated for the efficiency with which they deliver
      "therapeutic nucleotides" into their cellular targets. In this review, we recount
      some of the major developments that have occurred in these various areas and
      discuss their impact on progress in the field.

PMID- 8882307
TI  - Novel systems for controlled delivery of macromolecules.
AB  - Gene therapy promises new treatments for human disease by alterations in the DNA
      content of tissues. Methods for efficient and stable introduction of genes into
      target cells in the body are critically important in this effort. Researchers and
      physicians now have many years of experience with synthetic polymers for
      controlled drug delivery; many of these polymers can also be used to deliver
      macromolecules at controlled rates to tissues. This article reviews the use of
      polymers in controlled protein delivery and suggests ways that polymer delivery
      systems may be useful in the delivery of gene transfer agents.

PMID- 8882308
TI  - Drugs that target gene expression: an overview.
AB  - Over the last few years, it has become apparent that regulation of many normal
      physiological pathways, as well as the response to a wide variety of disease
      states, involves specific changes in gene transcription. The concept of drugs
      that regulate gene transcription is now firmly established. There are multiple,
      highly effective drugs in widespread use whose primary mechanism of action is to
      affect gene transcription. A major goal at Oncogene Science is to develop drugs
      that can modulate the normal physiological responses associated with disease by
      specifically increasing or decreasing the transcription of key genes. In this
      article, we review several examples of drugs that have been shown to act by
      regulating gene transcription and describe the approach Oncogene Science has
      pioneered.

PMID- 8882309
TI  - Regulation and regulatory role of gamma-carboxyglutamic acid containing clotting
      factors.
AB  - Blood coagulation is initiated following damage of the vessel wall. The large
      number of proteins that participate in the reactions that regulate blood
      coagulation must behave in a concerted manner to generate alpha-thrombin. This
      most abundant enzyme product of the coagulation process acts on the soluble blood
      protein fibrinogen to create the insoluble fibrin clot, trigger platelet
      activation, and initiate a variety of vascular processes ranging from coagulation
      inhibition and activation of fibrinolysis to cell growth. The majority of enzymes
      that participate in the blood-clotting process circulate in blood as inactive
      zymogens and procofactors. Following mechanical injury to the vessel wall, a cell
      associated protein, tissue factor, is exposed and initiates a series of enzymatic
      reactions localized on a membrane surface generally provided by cells and
      accumulating platelets. The binding of the enzymes and zymogen substrates to the
      exposed membrane surface and their activation are in part governed by the gamma
      carboxyglutamic acid residues (gla) of each protein. Recently, it has been
      demonstrated that the gla residues are necessary for Ca2+ binding and subsequent
      exposure of the hydrophobic membrane binding regions to the cell bilayer. Thus,
      the gla residues play a preeminent role during the blood-clotting process.
      Absence of gamma-carboxylation of one or more of the critical glutamic acid
      residues results in an impaired coagulation/anticoagulation process which may
      lead to a bleeding diathesis or thrombosis.

PMID- 8882310
TI  - Environmental pathogenesis of human retroviruses.

PMID- 8882311
TI  - Retroviral vaccines: challenges for the developing world.

PMID- 8882312
TI  - Roundtable: can experience with veterinary retroviral vaccines be applied to the
      human situation?

PMID- 8882313
TI  - Correlates of immune protection after vaccination with attenuated live murine
      leukemia virus.

PMID- 8882314
TI  - Efficacy of an inactivated feline leukemia virus vaccine.
AB  - An inactivated whole-virus FeLV vaccine, developed from a molecularly cloned FeLV
      isolate (FeLV-61E-A), was assessed for its ability to protect cats against
      homologous and heterologous virulent viral challenge. The fractions of cats that
      resisted the induction of persistent viremia after FeLV challenge were as
      follows: FeLV-61E-A vaccine, 95%; adjuvant controls, 26%; and established
      commercial control FeLV vaccine, 35%. The prechallenge mean neutralizing antibody
      titers for each group were as follows: FeLV-61E-A vaccine, 1:43; adjuvant
      controls, < 1:8; and commercial control FeLV vaccine, 1:12. The prototype FeLV
      61E-A vaccine was developed commercially for immunization of pet cats by
      substitution of a proprietary adjuvant and development of stable, high antigen
      production cell lines. This vaccine (Fel-O-Vax) has been studied extensively,
      alone and in multivalent combination with other feline virus vaccines, in seven
      efficacy trials involving a total of 150 immunized cats. These studies yielded an
      FeLV-resistant fraction of 87% in vaccinated cats as compared with 8% in adjuvant
      controls. The duration of immunity induced by an FeLV-61E-A commercial vaccine
      (Fel-O-Vax-LvK IV) was also assessed. One year after vaccination, 100% of
      challenged vaccinated cats and none of challenged controls resisted induction of
      persistent viremia. The results of these studies demonstrate that an inactivated
      FeLV vaccine prepared from a molecularly cloned subgroup A FeLV produces a high
      level of protective immunity against heterologous and homologous FeLV infection.
      This vaccine-induced immunity is durable for at least 1 year without intervening
      booster immunization or exposure to virus.

PMID- 8882315
TI  - The relevance of feline retroviruses to the development of vaccines against HIV.

PMID- 8882316
TI  - Comparative approach to retroviral vaccines.

PMID- 8882317
TI  - T cell-mediated destruction of bovine leukemia virus-infected peripheral
      lymphocytes by bovine leukemia virus env-vaccinia recombinant vaccine.

PMID- 8882318
TI  - Simian retrovirus vaccines: simian retrovirus and simian immunodeficiency
      lentivirus.

PMID- 8882319
TI  - Vaccine against human T cell leukemia-lymphoma virus type I: progress and
      prospects.

PMID- 8882320
TI  - Attenuated poxvirus vectors as carriers in vaccines against human T cell leukemia
      lymphoma virus type I.

PMID- 8882321
TI  - Replication in goats in vivo of caprine arthritis-encephalitis virus deleted in
      vif or tat genes: possible use of these deletion mutants as live vaccines.

PMID- 8882322
TI  - Characterization of protective and enhancing immune responses to equine
      infectious anemia virus resulting from experimental vaccines.

PMID- 8882323
TI  - Lentivirus replication in lymphoid tissue: use of lymphatic cannulation to study
      the initial stages of infection and immunity.

PMID- 8882324
TI  - Molecular studies of visna virus gene expression: analysis of envelope gene
      expression in transgenic sheep.

PMID- 8882326
TI  - Molecular characterization of field isolates of lentiviruses of small ruminants.

PMID- 8882325
TI  - Evaluation of vaccines for ovine lentivirus infection.

PMID- 8882327
TI  - Vaccination of cats with recombinant envelope glycoprotein of feline
      immunodeficiency virus: decreased viral load after challenge infection.

PMID- 8882328
TI  - Efficacy of recombinant feline leukemia virus vaccines.

PMID- 8882329
TI  - Accelerated viremia in cats vaccinated with recombinant vaccinia virus expressing
      envelope glycoprotein of feline immunodeficiency virus.

PMID- 8882330
TI  - Protection against human immunodeficiency virus type 2 and simian
      immunodeficiency virus in macaques vaccinated against human immunodeficiency
      virus type 2.

PMID- 8882331
TI  - Simian immunodeficiency virus live and inactivated experimental vaccines.

PMID- 8882332
TI  - Recombinant subunit vaccines against primate lentiviruses.

PMID- 8882333
TI  - "Attenuated" simian immunodeficiency virus in macaque neonates.

PMID- 8882334
TI  - An approach to vaccines against human immunodeficiency virus.

PMID- 8882335
TI  - Perspectives on retroviral pathogenesis and vaccines.

PMID- 8882336
TI  - Polymerase chain reaction to monitor repair of the HBV genome, the first step in
      viral replication.
AB  - A method based on the polymerase chain reaction (PCR) for evidencing repair of
      the hepatitis B virus (HBV) genome is described. Hepadnaviruses have a partially
      double-stranded relaxed circular genome (RC-DNA) which is converted into a
      covalently closed circular DNA (CCC-DNA) after entry of the virus into a target
      cell. Our aim was to set up a technique enabling us to determine whether possible
      in vitro replication of the virus in non-hepatic cells is initiated by formation
      of CCC-DNA. The relevant part of the strategy used for this PCR consisted of
      priming the HBV-DNA template with the same forward primer and with a reverse
      primer located either downstream or upstream from the minus strand gap. The CCC
      DNA form was found, as expected, in cells in which the virus was known to be
      actively replicating; although most sera contained only the RC-DNA form, it was
      also possible to evidence the CCC form. Such PCR amplification led to detection
      of 50-500 copies of the viral DNA. The method described should be useful in
      studying the biological fate of HBV in non-hepatic cells (considered as non
      permissive for virus replication), and in exploring the clinical significance of
      the presence of CCC-DNA in sera.

PMID- 8882337
TI  - Isolation and characterization of infectious full-length DNA clones of chimpanzee
      foamy viruses SFV6 and SFV7: evidence for a Taf-dependent internal promoter.
AB  - We have cloned complete viral genomes directly from Hirt supernatant DNAs of
      simian foamy virus types 6 and 7 (SFV6 and SFV7) -infected cells. These clones
      were shown to be infectious by transfection into cells and subsequent infection
      of susceptible cells either by cocultivation or by passage of cell-free
      supernatants. The presence of virus particles, suggested by a typical cytopathic
      effect, was confirmed by electron microscopy. These viruses were characterized at
      different levels of the replication cycle. The proviral genomes revealed a taf
      deletion comparable to that previously described in the human foamy virus (HFV)
      bel1 gene. Analysis of viral RNAs revealed similar patterns of transcripts for
      SFV6- and SFV7-infected cells, with predominant expression of accessory genes.
      Characteristic major viral polypeptides were identified by
      radioimmunoprecipitation for both isolates. Sequences homologous to the gene
      encoding Taf and to a potential internal promoter were identified in the
      infectious clones and subcloned into expression vectors. Their functional
      properties were tested by transfection assays, which provided evidence for the
      presence of a Taf-dependent internal promoter in both SFV6 and SFV7 isolates.

PMID- 8882338
TI  - In vitro studies on interferon-inducing capacity and sensitivity to IFN of human
      foamy virus.
AB  - We demonstrate in this article that human foamy virus (HFV) fails to induce
      interferon (IFN) production in two different human tissue culture cell lines:
      U373-MG and AV3. We also show the effect of human alpha-, beta- and gamma IFN on
      the multiplication cycle of HFV. Treatment of cells with 100 IU/ml of any IFN led
      to strong inhibition of an HFV-induced cytopathic effect. This effect was
      associated with a significant diminution of reverse transcriptase activity in
      supernatant fluids of IFN-treated infected cultures, and a substantial decrease
      in viral particle production, as detected by electron microscopy. All these
      effects were accompanied by strong inhibition of both viral proteins and RNA
      synthesis, as well as almost total disappearance of free and integrated proviral
      DNA. In light of our data, human IFN action on HFV seems to be mediated by a
      mechanism which differs from that observed in the case of other retroviruses
      (type C and D for instance); however, it evokes that described for HIV.

PMID- 8882339
TI  - Anti-HBe titre in patients infected with wild-type and e-minus variant of
      hepatitis B virus.
AB  - Serum samples from 77 HBsAg- and anti-HBe-positive chronic hepatitis B patients
      were studied for a G to A point mutation at the 1896 nucleotide of the precore
      region by polymerase chain reaction and oligonucleotide hybridization. Patients
      were grouped as: A, infected only by the wild-type virus; B, infected only by e
      minus variant; C, coinfected by the wild-type and e-minus variant; and D, no
      precore/core gene of hepatitis B virus detected. All samples were assayed for the
      titre of anti-HBe by ELISA and compared as grouped. A significantly higher titre
      was found in the coinfected group C compared to groups A (p < 0.01) and D (p <
      0.05). Results indicate that a high titre of anti-HBe is required as immune
      selective pressure for E-minus variant to overtake the wild-type virus.

PMID- 8882340
TI  - Clonal analysis suggests provirus expression in a subpopulation of human
      malignant trophoblast cells harbouring the human T cell lymphotropic virus type-I
      genome.
AB  - Previous studies have indicated that the villous trophoblast may be involved in
      intrauterine HTLV-I infection. Although the data furnished by our group (Liu et
      al., 1995) have demonstrated that the human trophoblast-derived malignant cell
      lines JAR and JEG-3 are susceptible to HTLV-I, the infection, even after thorough
      analysis, appeared to be limited to expression at the transcriptional level. In
      the present report, we sought to explore virus expression at the single cell
      level using eight clonally selected cell lines which were derived by limiting
      dilution from the previously infected parental cultures. Of the three cell lines
      JAR-H2, JAR-H3, and JEG-H3, all of which harboured full-length provirus, only in
      two (JAR-H2 and JEG-H3) were the virus-specific tax/rex and env transcripts
      demonstrated using RT-PCR. When compared with MT-2 cells, the detected steady
      state levels of HTLV-I mRNA appeared to be lower by three orders of magnitude.
      Viral Tax protein displaying a typical intranuclear localization was found in 1
      2% of JAR-H2 and JEG-H3 cells. Moreover, an altered phenotype characterized by
      multinucleated syncytia was observed in these cell cultures with the same
      frequency as Tax transactivator, implying a fusogenic activity of env protein.
      Infectious virus, however, could not be rescued from JAR-H2 or JEG-H3 clones by
      coculture with cord blood mononuclear cells. Our data suggest that trophoblast
      represents a susceptible, albeit a slightly permissive, host system for HTLV-I.

PMID- 8882341
TI  - Compact Epstein-Barr virus diagnosis based on a defined antigen mix and specific
      IgA.
AB  - An ELISA was evaluated to measure EBV-specific IgM, IgG and IgA using a test
      plate coated with a controlled mix of EA, VCA and EBNA. Using the IgM version,
      the multi-reactive surface reduced false-negative findings in cases of infectious
      mononucleosis (sensitivity 98%), but was confronted with polyclonal IgM responses
      (specificity 85% to 95% depending on the population). For the IgG version, a
      national research standard was involved, and in combination with the IgA
      estimation, a new diagnostic strategy became possible for chronic EBV infections
      and reactivations. Patients screened by enhanced IgG (> 650 U/ml) were confirmed
      by an elevated IgA signal (> 0.6 A), with an efficacy of 95%. A raised virus
      specific IgA response was not observed in cases of infectious mononucleosis, but
      was seen for healthy HIV-positive persons. Superior to the traditional antibody
      puzzle for EBV diagnosis, it will now become possible, using this compact
      diagnostic concept, to reduce laboratory expenses without loss of reliable
      results.

PMID- 8882342
TI  - CD26 and HIV infection.

PMID- 8882343
TI  - Effect of aluminium hydroxide administration on normal mice: tissue distribution
      and ultrastructural localization of aluminium in liver.
AB  - In order to assess the risk of parenteral aluminium (Al) exposure, we evaluated
      the effects of intraperitoneal administration of aluminium hydroxide, a compound
      widely used in medicine. Mice (strain Pzh:SFIS) received intraperitoneally, every
      two weeks 1 mg Al or 0.1 mg Al for five days a week. Controls received injections
      of saline. Al concentrations in liver, bone and brain were evaluated by
      electrothermal atomic absorption spectrometry after exposure to 2 mg, 4 mg, and 6
      mg Al. The concentration was the highest in liver and occurred after exposure to
      only 2 mg Al (265.1 +/- 27.7 mg/kg, 233.5 +/- 28.0 mg/kg). Generally further
      accumulation was not dose- and treatment-dependent. The only exception was a
      significant Al increase in the liver after exposure to 6 mg Al, injected 0.1 mg
      Al five days/week. Development of resorption granulomas was observed in the
      liver, Al being revealed by Morin fluorescence in constituent macrophages and
      giant cells. By electron probe X-ray microanalysis, Al was identified
      predominantly in lysosomes of macrophages and Kupffer cells. In tibia of mice, a
      dose-dependent Al accumulation was observed. The highest level of Al
      concentration after the 6 mg treatment was 23.5 +/- 3.82 mg/kg and 25.06 +/- 2.3
      mg/kg. The Al concentration in the brain of mice had not changed significantly
      during Al treatment.

PMID- 8882344
TI  - Morphine withdrawal alters anterior pituitary hormone secretion, brain
      endopeptidase activity and brain monoamine metabolism in the rat.
AB  - Rats were made tolerant to morphine by a 5-day regimen with increasing doses. The
      time course of changes in serum anterior pituitary hormone levels, brain endo-
      and exopeptidase activity, levels of brain biogenic amines and body weight were
      studied during abrupt morphine withdrawal. Cold stimulated secretion of
      thyrotropin and the secretion of growth hormone were both decreased whereas that
      of prolactin was increased. In the hypothalamus both prolyl endopeptidase and
      dipeptidyl peptidase IV activities were concomitantly increased. The hypothalamic
      5 hydroxyindole acetic acid levels were also increased. Changes in hormone
      secretion, peptidase activity and monoamine turnover had returned to baseline
      levels by 92 hr. Our results indicate that morphine withdrawal and the associated
      stress produce alterations in anterior pituitary thyrotropin and growth hormone
      secretion. Concomitant increases in hypothalamic prolyl endopeptidase and
      dipeptidyl peptidase activities may contribute to these changes.

PMID- 8882345
TI  - Neuroendocrine effects of dexmedetomidine: evidence of cross-tolerance between a
      mu-opioid agonist and an alpha 2-adrenoceptor agonist in growth hormone secretion
      of the male rat.
AB  - The role of alpha 2-adrenergic receptors (adrenoceptors) in the secretion of
      growth hormone, prolactin and thyrotropin was studied using highly selective
      agonists and antagonists of the alpha 2-adrenoceptor. The interplay between
      opiates and alpha 2-adrenergic drugs in the acute secretion of growth hormone and
      prolactin, as well as the possible cross-tolerance between morphine (mu-opioid
      receptor agonist) and dexmedetomidine (alpha 2-adrenoceptor agonist) in growth
      hormone secretion were also evaluated. Dexmedetomidine dose-dependently increased
      plasma growth hormone and prolactin levels and decreased thyrotropin levels. The
      enhanced secretion of both growth hormone and prolactin was antagonized by
      atipamezole (an alpha 2-adrenoceptor antagonist) but not by prazosin (an alpha 1
      adrenoceptor antagonist). Morphine (5 mg/kg)-induced stimulation of growth
      hormone secretion was antagonized by both naloxone (mu-opioid antagonist) and
      atipamezole. Naloxone, but not atipamezole, antagonized the morphine-induced
      increase in prolactin secretion. Dexmedetomidine increased growth hormone
      secretion in the saline pretreated rats, but did not do so in the morphine
      tolerant rats. The stimulation of alpha 2-adrenoceptor enhances secretion of both
      growth hormone and prolactin. The adrenergic regulation of thyrotropin secretion
      still remains unclear. Evidently, adrenergic mechanisms are involved in the
      morphine-induced stimulation of growth hormone secretion, but not in the morphine
      induced stimulation of prolactin secretion. In addition, there is a clear cross
      tolerance between dexmedetomidine and morphine in growth hormone secretion of the
      rat.

PMID- 8882346
TI  - Inhibition of low density lipoprotein oxidation by myrigalone B, a naturally
      occurring flavonoid.
AB  - The influence of myrigalone B, a flavonoid from the fruit exudate of Myrica gale
      L. on Cu(2+)-induced oxidation of low density lipoprotein from cholesterol fed
      rabbits was investigated. Myrigalone B was an effective antioxidant, as shown by
      its ability to dose-dependently prolong the lag time for the formation of
      conjugated dienes. A 100% increase in lag time corresponds to a myrigalone B
      concentration of 1.4 +/- 1.1 microM. For alpha-tocopherol, used as a reference,
      this effect corresponds to a concentration of 1.9 +/- 1.2 microM. Myrigalone B
      also dose-dependently reduced the maximum rate of formation of conjugated dienes,
      1.4 microM causing a 15 +/- 5% reduction, but it had no influence on the maximal
      amount of conjugated dienes formed.

PMID- 8882347
TI  - Effects of calcium channel modulators on the regulation of cytoplasmic Ca2+ and
      hormone secretion of parathyroid cells.
AB  - Effects of Ca(2+)-channel modulators were examined in human, bovine and murine
      parathyroid tissue. In 0.5 mM external Ca2+, 100 microM verapamil inhibited
      parathyroid hormone release, stimulated uptake and efflux of 45Ca and raised
      cytoplasmic Ca2+ concentration ([Ca2+]i). However, in 3.0 mM Ca2+ the drug only
      affected efflux. Methoxyverapamil (50 microM) inhibited parathyroid hormone
      release in 0.5 mM but stimulated secretion in 3.0 mM Ca2+. BAY K 8644 (10 microM)
      had similar actions as verapamil on parathyroid hormone release and [Ca2+]i,
      whereas nifedipine (1 microM) and diltiazem (50-100 microM) lacked effects.
      Despite the lack of voltage-dependent Ca2+ channels in parathyroid cells, drugs
      with established actions on such channels affect [Ca2+]i and parathyroid hormone
      release. However, these actions are not sufficiently pronounced and tissue
      specific to allow their use for correcting hyperparathyroidism.

PMID- 8882348
TI  - Arsenic-copper interaction in the kidney of the rat: influence of arsenic
      metabolites.
AB  - The present study was an attempt to investigate whether the renal accumulation of
      Cu observed in the kidneys of rats and guinea-pigs exposed to arsenite (As-III)
      was an effect of arsenite alone or also shared by its metabolites--arsenate (As
      V), dimethylarsinic acid and monomethylarsonic acid. The four arsenic compounds
      were administered subcutaneously and separately to rats for 12 days in increasing
      doses. Kidney, liver and blood were taken and analysed for As, Cu and other trace
      elements by atomic emission spectrometry. Results indicate that administration of
      As-V leads to renal Cu accumulation similar to that observed on administration of
      As-III and that the accumulation in both cases is dependent on the dose of
      arsenic, although higher doses of As-V were required to achieve renal Cu levels
      comparable to that of As-III. A constant molar As:Cu ratio independent of arsenic
      dose was obtained in the kidney. Dimethylarsinic acid did not affect renal Cu
      levels at all. Administration of monomethylarsonic acid led to a slight increase
      in renal Cu levels which did not increase further in spite of increased doses of
      monomethylarsonic acid. It is concluded from these studies that neither the
      metabolic transformation of inorganic arsenic to its methylated products nor its
      metabolites (dimethylarsinic acid and monomethylarsonic acid) caused the observed
      renal Cu accumulation, rather, the inorganic form of As, either in the trivalent
      or pentavalent form is responsible.

PMID- 8882349
TI  - Effect of dopexamine hydrochloride on sympathetic neuroeffector transmission in
      rabbit isolated pulmonary artery.
AB  - The effects of dopexamine hydrochloride on sympathetic neuroeffector transmission
      were studied in rabbit isolated pulmonary artery. Short-term exposure of
      dopexamine (10(-8) x 10(-7) M) and cocaine (10(-6)-3 x 10(-5) M), but not
      desipramine (3 x 10(-9)-3 x 10(-7) M), to the artery enhanced the contractions
      evoked by electrical-field stimulation. Corticosterone (4 x 10(-5) M),
      corticosterone (4 x 10(-5) M) plus cocaine (3 x 10(-8) M), but not cocaine (3 x
      10(-5) M), attenuated the enhancement seen with dopexamine. High concentrations
      of dopexamine (10(-5)-3 x 10(-5) M), cocaine (10(-4) M), and desipramine (10(-6)
      10(-5) M) decreased the stimulation-evoked contractions. Dopexamine (10(-7)-3 x
      10(-5) M), but neither cocaine nor desipramine, caused an increase in resting
      tension that waned with time. Corticosterone (4 x 10(-5) M), but not cocaine (3 x
      10(-5) M), attenuated the increase in resting tension. Propranolol (10(-6) M) did
      not alter the enhancing and inhibitory effects of dopexamine. A single
      concentration (10(-7) and 10(-6) M) of either dopexamine or desipramine caused a
      time-dependent biphasic response as regards the repetitive stimulation-evoked
      contractions of pulmonary artery: initial enhancement followed by inhibition. The
      inhibitory effect of dopexamine (10(-6) M) and desipramine (3 x 10(-6) M) seen
      after prolonged exposure was almost irreversible and partially reversible,
      respectively, by washing the preparations with drug-free salt solution. Cocaine
      caused a monophasic steady-state response: either enhancement (10(-5) M) or
      inhibition (2 x 10(-4) M). In both cases, the onset was rapid. The reduction
      caused by cocaine (2 x 10(-4) M) and by prazosin (10(-9) M) was fully reversed.
      Dopexamine (10(-5) M) antagonized competitively the contractions evoked by
      noradrenaline (3 x 10(-9)-10(-4) M). It is concluded that (1) the dopexamine
      induced enhancement of neurogenic contractions is not due to either inhibition of
      neuronal and extraneuronal uptake of noradrenaline or an agonist action on
      prejunctional beta 2-adrenoceptors; (2) that the dopexamine-induced inhibition of
      stimulation-evoked contraction is due to an inhibition of postjunctional alpha 1
      adrenoceptors; and (3) that the dopexamine-induced increase in resting tension is
      due to its metabolite methyldopexamine.

PMID- 8882350
TI  - Interaction between opioid and muscarinic receptors in the guinea-pig ileum
      preparation: a mathematical model.
AB  - Fentanyl and pethidine are opioid agonists and muscarinic antagonists in the
      guinea-pig ileum preparation. In this preparation an opioid agonist reduces the
      release of acetylcholine. Therefore an opiate may influence the potency of an
      anticholinergic drug. A mathematical model was developed to characterize this
      putative interaction between opioid and muscarinic receptors. The model is based
      on the assumption that the drugs interact with the receptors in a competitive
      manner according to the law-of-mass action. Concentration-response experiments
      were performed in the guinea-pig ileum preparation to test the model. The
      mathematical model describes the concentration-response curves very well and
      estimates the IC50 values for the two components with good precision. The study
      shows that an opioid agonist can potentiate the effect of an anticholinergic drug
      substantially. This is interesting with regard to the central anticholinergic
      syndrome. The conclusion is that the model describes the interaction adequately.

PMID- 8882351
TI  - Nephroprotective mechanism(s) of pentoxifylline: reduction of erythrocyte
      mediated vascular congestion and inhibition of nitric oxide release.
AB  - The present study attempted to evaluate pentoxifylline's mechanism(s) of action
      in the prevention of acute renal failure by examining its vascular decongestant
      activity in a rat model for acute renal failure and inhibitory activity of nitric
      oxide release from activated macrophage-like (RAW 264.7 cells) and murine mammary
      adenocarcinoma (EMT-6 cells) cell lines. Radiolabeled chromium-erythrocytes were
      injected intravenously into all rats. Following occlusion of the left kidney for
      45 minutes, rats were treated with pentoxifylline or normal saline. The medulla
      of the left (ischaemic) kidney had significantly higher radioactive counts than
      the right (control kidney) following an intravenous dose of normal saline. The
      medulla to whole blood radioactivity ratio of the left kidney was significantly
      greater than for the right (control) kidney. Animals administered intravenous
      pentoxifylline (5 mg/kg) had significantly lower radioactive counts in the
      medulla of the left (ischaemic) kidney than animals administered intravenous
      normal saline. No differences in radioactivity counts in the medulla of the left
      (ischaemic) kidney were observed when animals received intraperitoneal
      pentoxifylline (45 mg/kg) versus normal saline. In a second set of experiments
      the nitrite synthesis and percent cytotoxicity of pentoxifylline- and
      dexamethasone-treated cells were determined. Pentoxifylline at concentrations of
      4 mM and 8 mM significantly decreased nitrite synthesis in RAW 264.7 cells, and
      at pentoxifylline concentrations of 2 mM, 4 mM, and 8 mM in EMT-6 cells compared
      to untreated cells. Dexamethasone at a concentration of 1 microM decreased
      nitrite synthesis in RAW 264.7 and EMT-6 cells compared to untreated cells.
      Pentoxifylline at concentrations of 0.5 mM through 8 mM significantly decreased
      cytotoxicity in RAW 264.7 and EMT-6 cells compared to untreated cells.
      Dexamethasone at a concentration of 1 microM decreased cytotoxicity in RAW 264.7
      and EMT-6 cells compared to untreated cells. These finding suggest that
      pentoxifylline's ability to prevent acute renal failure may be a consequence of
      reduced vascular congestion and inhibition of nitric oxide release from activated
      macrophages.

PMID- 8882352
TI  - Milk transfer and neonatal uptake of coplanar polychlorinated biphenyl (PCB)
      congeners in mice.
AB  - The selective accumulation of 3,3',4,4'-tetrachlorobiphenyl metabolites in late
      gestational foetal blood and soft tissues in mice as a result of administration
      of different coplanar polychlorinated biphenyl (PCB) congeners, is reported
      elsewhere. The situation in the nursing neonate after maternal exposure to the
      same congeners is now studied: The 14C-labelled congeners 3,3',4,4'
      tetrachlorobiphenyl (IUPAC number CB-77),3,3',4,4'5-pentachlorobiphenyl (IUPAC
      number CB-126), 3,3',4,4',5,5'-hexachlorobiphenyl (IUPAC number CB-169) (all
      three non-ortho congeners) and 2,3,3',4,4'-pentachlorobiphenyl (IUPAC number CB
      105) (mono-ortho congener) were injected intravenously in lactating mice at day
      11 post partum. One day and four days later, milk and neonatal/maternal tissues
      and plasma radioactivity was monitored by liquid scintillation counting (dose:
      2.0 mumol (20-50 microCi)/kg body weight). In milk, CB-126, -169 and -105 showed
      higher levels (1450-2520 pmol/ml; one day after administration) than did CB-77
      (580 pmol/ml), and in neonates, the relative whole-body levels of radioactivity
      (CB-169 and -105 highest) were related to the levels seen in milk (probably the
      consequences of their metabolic persistence). The comparably high 14C
      concentration found in neonatal liver (about 15,000 pmol/kg) after CB-126
      administration and in plasma (880 pmol/ml) after CB-77 administration could be
      explained by binding to specific proteins. In general, neonatal mice had two to
      seven times higher plasma levels than those of their mothers. These results
      indicate that CB-126, -169 and -105 are transferred via milk to neonates in
      considerable quantity and are deposited mainly in neonatal liver, whereas CB-77
      is transferred in a comparably lower amount and accumulated in neonatal plasma.
      The lower 14C-levels in the NMRI mothers and offspring (about half of C57BL
      values in maternal and neonatal plasma), could possibly be explained by a
      differentiated metabolism of CB-77 in these two strains.

PMID- 8882353
TI  - Foetal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice.
AB  - Earlier studies (Darnerud et al. 1986) have shown that the Ah-receptor binding
      polychlorinated biphenyl (PCB) congener 3,3',4,4'-tetrachlorobiphenyl (IUPAC
      number CB-77) accumulated as hydroxy and methylsulphone metabolites in late
      gestational mice foetuses. In the present paper the foetal accumulation potential
      in mice of other dioxin-like PCB congeners was studied: 3,3',4,4',5
      pentachlorobiphenyl, 3,3',4,4',5,5'-hexachlorobiphenyl and 2,3,3',4,4'
      pentachlorobiphenyl (IUPAC numbers CB-126, CB-169, CB-105, to some extent dioxin
      like) were compared to results of CB-77 (all congeners 14C-labelled and in
      equimolar doses (2.0 mumol/kg body wt.)). CB-77 resulted in the comparatively
      strongest foetal 14C-accumulation, when measured in plasma or whole body
      homogenate four days after administration (day 17 of pregnancy); the plasma 14C
      values (calculated as pmol/g wet wt.) were 760, 130, 60 and 40 for CB-77, -126,
      105 and -169, respectively, and the CB-77 derived radioactivity in the foetal
      compartment was 3.6% of administered dose (i.e. a considerable portion of the
      remaining maternal body radioactivity). Thin-layer chromatography (TLC) results,
      suggesting extensive CB-77 metabolism and foetal metabolite uptake, support
      earlier findings. The effects of CB-77 and CB-169 on foetal 7-ethoxyresorufin-O
      deethylase (EROD) activities (day 17 of gestation; two days after 5 mg/kg body
      wt. dose (14.0-17.0 mumol/kg body wt.)) was about 20 times lower than of CB-126.
      In the dam, high radioactivity levels were observed in the liver and fat (highest
      concentrations found in CB-126 and CB-105, respectively). Strain comparison
      foetal 14C-uptake (four days after administration of CB-77) in C57BL mice was
      almost five times higher than in NMRI-may be correlated to earlier observed
      differences in EROD activities between these strains. The present results
      indicate that congener and strain differences exist regarding both foetal and
      maternal distribution patterns of coplanar PCB congeners and point out the
      difference in foetal disposition between CB-77 and the other studied congeners.

PMID- 8882354
TI  - Protective effects of Ca2+ channel blockers against methyl mercury toxicity.
AB  - The protective effects of Ca2+ channel blockers against the toxicity of methyl
      mercury were examined by both in vivo and in vitro experiments. In the in vivo
      study we first examined the effects of the Ca2+ channel blockers (20 mg/kg/day),
      flunarizine, nifedipine, nicardipine, and verapamil against the toxic level of
      methyl mercury treatment (5 mg/kg/day of methyl mercuric chloride for 12
      consecutive days). However, there was a difference in potency of the effects
      among the reagents. All the Ca2+ channel blockers prevented a decrease in body
      weight and/or the appearance of the symptoms of neurological disorders in the
      rats treated with methyl mercury. In the next experiment, we examined flunarizine
      at different levels of supplementation (1, 25 and 50 mg/kg/day). Flunarizine in a
      dose-dependent manner prevented a decrease in body weight, appearance of the
      symptoms of neurological disorder and mortality in the rats treated with methyl
      mercury. Flunarizine treatment (25 mg/kg/day) for the first 5 days did not affect
      mercury distribution among the tissues, suggesting that the mechanism of
      protection against methyl mercury-induced toxicity may be attributed to its own
      pharmacological effect. In the in vitro study we examined the effect of
      flunarizine (0, 0.5, 5 and 50 microM) using primary cultures of cerebellar
      granular cells in 96-well culture plates. Viable cell numbers were estimated 1
      and 3 days after treatment with methyl mercury. The estimated 50% lethal
      concentration (LC50) of methyl mercury was higher in plates treated with 5 and 50
      microM of flunarizine both on days 1 and 3, indicating that flunarizine protected
      the primary cultured cerebellar granular cells against the toxicity of methyl
      mercury. As such, Ca2+ channel blockers protected against the toxicity of methyl
      mercury both in vivo and in vitro, suggesting that Ca2+ plays an important role
      in the mechanisms of methyl mercury toxicity.

PMID- 8882355
TI  - Tetrandrine inhibits lipid peroxidation but lacks reactivity towards superoxide
      anion and hydrogen peroxide.

PMID- 8882356
TI  - Trichomoniasis complicating esophageal intramural pseudodiverticulosis: diagnosis
      by transmission electron microscopy.
AB  - A 58-year-old African-American man presented with a progressive esophageal
      stricture of unknown etiology complicated by esophageal candidiasis, broncho
      esophageal fistula, four episodes of aspiration pneumonia, and a 40-lb weight
      loss. He ultimately required an esophagectomy. Pathologic examination showed
      marked thickening of the esophageal wall by submucosal pseudodiverticula typical
      of esophageal intramural pseudodiverticulosis (EIPD) and extensive mucosal and
      submucosal chronic inflammation and fibrosis. Small, oval cells with ill-defined
      nuclei were present in lumens of some pseudodiverticula, light microscopically.
      Their exact nature could not be determined by light microscopy. The diagnosis of
      trichomoniasis became apparent only after transmission electron microscopic study
      of these cells demonstrated characteristic features of trichomonad protozoa.
      These included four anteriorly placed flagella with kinetosomes, a recurrent
      flagellum associated with an undulating membrane, a costa, a peltar-axostylar
      complex, and a small Golgi body with parabasal filaments. This case of EIPD is
      unusual in that the associated broncho-esophageal fistula and trichomoniasis have
      not been previously reported as complications of EIPD.

PMID- 8882357
TI  - Correlation of subcellular and intratumoral photosensitizer localization with
      ultrastructural features after photodynamic therapy.
AB  - Photodynamic therapy (PDT) of cancer typically involves systemic administration
      of tumor-localizing photosensitizers followed 48-72 h later by exposure to light
      of appropriate wavelengths. Knowledge about the distribution of photosensitizers
      in tissues is still fragmentary. In particular, little is known as to the
      detailed localization patterns of photosensitizers in neoplastic and normal
      tissues as well as the relationship between such patterns and the actual targets
      for the photosensitizing effect. This review focuses on ultrastructural features
      seen in treated cells and tumors. An attempt is made to correlate these findings
      with the subcellular/intratumoral localization pattern of the photosensitizers in
      tumor cell lines in vitro and in tumor models in vivo. Several subcellular sites
      are main targets of PDT with different sulfonated aluminum phthalocyanines
      (AIPcSn) in the human tumor cell line LOX. Nuclei are not among the primary
      targets. Overall, the ultrastructural changes correlate well with the data about
      the subcellular localization patterns for each analogue of AIPcSn in the same
      cell line. Similar findings are also obtained for the family of sulfonated
      mesotetraphenylporphines (TPPSn) in the NHIK 3025 cell line. The mechanisms
      involved in the killing of tumors by PDT seem to be a complex interplay between
      direct and indirect (via vascular damage) effects on neoplastic cells according
      to the intratumoral localization pattern of the applied dye. Several factors can
      affect the localization pattern of a drug, such as its chemical character, the
      mode of drug delivery, the time interval between drug administration and light
      exposure, and tumor type. Furthermore, whether local immune reactions (such as
      macrophages) and apoptosis (programmed cell death) are involved in the
      destruction of neoplastic cells by PDT in vivo is still an enigma. A general
      model for PDT-induced tumor destruction is suggested.

PMID- 8882358
TI  - Variability of differentiation patterns in xenotransplanted spindle cell
      sarcomas: a histomorphological, immunohistochemical, and ultrastructural study.
AB  - Three leiomyosarcomas, 3 nerve sheath sarcomas, 1 rhabdomyosarcoma, and 1 sarcoma
      not otherwise classifiable with 17 of their xenografts, grown on nude mice, were
      analyzed to assess the degree of concordance between histomorphology,
      immunohistochemistry, and ultrastructure in spindle cell sarcoma xenograft
      differentiation. Histomorphology was inconclusive or misleading in 4/8 sarcoma
      strains and immunohistochemistry in 4/8 originals and in 10/17 xenografts,
      although specific patterns had been identified ultrastructurally. Electron
      microscopy was superior to immunohistochemistry and histomorphology in spindle
      cell sarcoma differential diagnosis. A further purpose of this study was to
      clarify whether spindle cell sarcoma xenografts retain the morphological
      characteristics of their primaries. Histomorphological features of the primaries
      were preserved over all passages, whereas the immunohistochemical marker profiles
      as well as the ultrastructural phenotypes changed in 14/17 xenografts and in 8/17
      xenografts, respectively. Moreover, unusual bidirectional or tridirectional
      patterns of differentiation were identified ultrastructurally with leiomyomatous
      as well as Schwann cells occurring side by side and with MFH-like areas in 5/17
      xenotransplants. These findings suggest genetic instability of tumor cells and
      may be important in the consideration of mesenchymal differentiation pathways.

PMID- 8882359
TI  - Primary small cell neuroendocrine carcinoma of the kidney.
AB  - The histological, immunohistochemical, and ultrastructural features of a primary
      small cell neuroendocrine carcinoma of the renal parenchyma are described. Tumor
      cells were positive for cytokeratin, neuron-specific enolase, and Leu 7, but
      Grimelius- and chromogranin-negative. They also exhibited positivity with anti
      MIC2 antibody. By electron microscopy, tonofibrils, primitive desmosomes, and
      dense-core granules with a neuroendocrine appearance were present. This is only
      the 7th recorded example of such a tumor at this site, which showed an aggressive
      course characterized by widespread bony metastases.

PMID- 8882360
TI  - Myoepithelial carcinoma arising in a benign myoepithelioma: immunohistochemical,
      ultrastructural, and flow-cytometrical study.
AB  - A case of myoepithelial carcinoma arising in a benign myoepithelioma of the minor
      salivary gland in a 71-year-old patient is reported. The tumor presented
      initially on the palate and had been diagnosed as "benign lesion" 40 years
      before. It recurred 22, 36, and 40 years after initial presentation, and a
      similar histopathological diagnosis was rendered. One year after the last
      recurrence, the tumor recurred showing typical changes of malignant
      transformation, and the diagnosis was malignant myoepithelioma. The light
      microscopy and ultrastructural features of the initial tumor were typical of
      plasmocytoid myoepithelioma. There were abundant round cells and rare spindle
      cells with uniform dispersed filaments, sometimes arranged in parallel streams
      without evidence of dense bodies. These cells showed micropinocytotic vesicles
      along the cell membrane with poorly developed intercellular junctions and were
      surrounded by a basal membrane. The malignant counterpart showed fewer
      plasmocytoid cells and a rather epithelial pattern with marked nuclear
      pleomorphism and formation of small, or rarely large, glandular lumina. The
      immunohistochemical features were similar for the benign and malignant tumors,
      with positivity for S-100 protein, vimentin, cytokeratins, and CAM 5.2, and were
      negative for GFAP, muscle-specific actin, CEA, and desmin. Flow cytometry showed
      a change in the DNA content profile. The benign myoepithelioma had a diploid DNA
      content with a low S-phase fraction of 3.9% and proliferative index of 9.1%,
      while the myoepithelial carcinoma had an evident aneuploid DNA stem line and an
      increased S-phase fraction of 8.3% with a proliferative index of 18.1%.

PMID- 8882361
TI  - Extrarenal Wilms' tumor: an ultrastructural and immunoelectron microscopic case
      report.
AB  - Wilms' tumor is the most common malignancy of the genitourinary tract in children
      but the occurrence of extrarenal Wilms' tumor is extremely rare. Extrarenal
      Wilms' tumor, which by definition excludes a primary tumor in the kidney, has
      been reported less than fifty times. The ultrastructural appearance of renal
      Wilms' tumor has been well documented, but the present report is believed to be
      the first description of the ultrastructural appearance of extrarenal Wilms'
      tumor. The authors report, for the first time, localization of intermediate
      filament proteins (vimentin and cytokeratin) and epithelial membrane antigen
      (EMA) by immunoelectron microscopy in this neoplasm. Demonstration of the
      coexpression of vimentin and cytokeratin within the same blastemal cell, as well
      as the identification of desmosomes in a cell with vimentin intermediate
      filaments, suggests a relationship between stroma, blastema, and epithelia
      similar to that proposed in renal Wilms' tumor.

PMID- 8882362
TI  - Ultrastructural study of a perineurioma with ribosome-lamella complexes.
AB  - The participation of the perineurial cell in peripheral nerve tumors is the
      subject of much debate. The case of a 75-year-old female with a soft tissue tumor
      on her left shoulder is presented. The tumor had histological, ultrastructural,
      and immunohistochemical characteristics of a pure perineurial cell neoplasm.
      Ultrastructurally, distinctive ribosome-lamella complexes were found in the
      cytoplasm of the perineurial cells. This may be the first time that these
      structures have been described in perineurioma.

PMID- 8882363
TI  - Ribosome-lamella complexes in the perineurial cells of neurofibromatosis.
AB  - Ribosome-lamella complexes are occasionally seen in neoplastic disorders of the
      hematopoietic system, particularly in hairy cell leukemia. However, these
      structures are rare in epithelial and mesenchymal cells. In this report three
      tumors from a patient with neuro-fibromatosis (von Recklinghausen's disease) are
      examined by electron microscopy. Ribosome-lamella complexes were seen in the
      perineurial cells. This may be the first report of these complexes in nerve
      sheath tumors.

PMID- 8882364
TI  - Ultrastructural study of the osteointegration of bioceramics (whitlockite and
      composite beta-TCP + collagen) in rabbit bone.
AB  - Study examines the osteointegration of two porous ceramic implants, beta
      tricalcium phosphate (beta-TCP) and a composite (beta-TCP-collagen), in femur and
      tibias of 20 New Zealand white rabbits, which were sacrificed 1 week and 1, 4,
      and 12 months postimplant so that radiological, optical microscopic, and
      ultrastructural studies could be carried out. The results show a progressive
      degradation and resorption of both implant materials by means of a macrophagic
      reaction, which is at its most intense 1 month postimplant. The materials are
      substituted by newly formed bone tissue starting at the host bone-implant
      interface, the substitution being almost total by the end of the study, although
      less completely and earlier than in the case of the composite. Both materials can
      be considered as potential substitutes for bone tissue since they are
      biocompatible, bioreabsorbable, and osteogenic.

PMID- 8882365
TI  - Diagnosis of an anemone cell tumor as a B-cell lymphoma by molecular analysis.
AB  - An 83-year-old man presented with mediastinal and axillary lymphadenopathy.
      Immunophenotyping and electron microscopy performed on an excision biopsy were
      inconclusive. On a repeat biopsy a year later the ultrastructural features
      typical of an anemone cell tumor were seen. A panel of monoclonal antibodies
      showed positivity for vimentin only. The diagnosis of a high-grade B-cell
      lymphoma could be made only after detection of immunoglobulin gene rearrangement
      by polymerase chain reaction gene amplification.

PMID- 8882366
TI  - Studies on samh seeds (Mesembryanthemum forsskalei Hochst) growing in Saudi
      Arabia: 3. Utilization of samh seeds in bakery products.
AB  - Samh seeds obtained from Al-Jouf area were ground into flour analyzed and used as
      a replacement for wheat in the ratio of 10, 20 and 30% for bread and 30, 60 100%
      for cookies. The rheological effect of the Samh flour on Saudi wheat flour was
      also studied. The bread and cookies obtained were evaluated physically and by
      sensory evaluation. The results obtained indicated that samh flour has high
      protein content and could be used as a replacement for wheat flour upto 30%
      without adversely affecting the bread specific volume much. Samh flour has
      improved the cookies appearance specially the colour (chocolate colour) and
      spreading ratio. The results also revealed that it is possible to make cookies
      from 100% samh flour. Due to the high protein content of the samh seeds the
      nutritional value of the bread and cookies made with samh flour will be improved.
      The results of the sensory evaluation of the bread and cookies indicated that the
      bread made with samh flour upto 30% has similar characters except for the crumb
      color and the overall acceptability which were rated as significantly inferior.
      The sensory evaluation of the cookies showed that the cookies made with samh
      flour upto 100% were significantly superior (p < 0.05) to the cookies made with
      100% wheat flour (control).

PMID- 8882367
TI  - Protein profiles and organoleptic properties of bread from wheat flour and full
      fat or defatted fermented cocoa bean powder.
AB  - This study has shown that the protein in bread may be quantitatively increased
      significantly by addition of full-fat or defatted cocoa powder to white flour.
      The recipe in which white flour is incorporated with up to 10 percent defatted
      cocoa powder gives bread that is nearly as well accepted as white bread, but with
      a significantly higher protein content than the latter. However, organoleptic
      acceptability drops with increasing percentage of cocoa supplementation. The
      bitter taste of theobromine, which is normally present in high amounts in cocoa
      bean, is thought to be responsible for this problem of poor acceptability of high
      cocoa breads. This problem will have to be addressed in order to enhance the
      scope of increasing bread protein by cocoa supplementation.

PMID- 8882368
TI  - Protein quality of some Nigerian traditional diets based on the African yambean
      (Sphenostylis stenocarpa) and pigeon pea (Cajanus cajan).
AB  - The protein quality of Nigerian traditional diets based on the African yambean
      (AYB) and pigeon pea (PP) were performed by in vivo and in vitro bioassays. The
      individual foods were processed, cooked, dried and mixed to resemble the
      traditional diets. Weanling male Wistar rats (45-55 g) were used for the
      bioassay. The rats were fed ad libitum for 35 days of which 28 days were for
      growth and 7 days for N-balance. All the eleven diets including casein (control)
      provided 1.6 g N/100 g diet. The parameters tested include PER, growth, N
      balance, BV, NPU and apparent digestibility (AD). The rats fed the AYB diets,
      except AYB: Agidi (Ag), showed superiority in most of the parameters tested.
      There were significant positive correlations between PER and NPU (r = 0.925; p <
      0.001); PER and AD (r = 0.908; p < 0.001); PER and body weight gain (r = 0.969; p
      < 0.001). The in vitro protein digestibility of the diets was significantly
      correlated (r = 0.80; p < 0.01) with the in vivo apparent digestibility. These
      parameters were used to rank the various diets. Crayfish protein was a better
      supplement to legume/cereal or legume starchy staple mixtures than leguminous oil
      seed. However, supplementation of PP: steamed corn (SC) diet with crayfish did
      not prove beneficial. The result showed that diets based on the African yambean,
      an under-exploited legume, are nutritious. The need for its reintroduction into
      the fare of the populace through increased production and appropriate processing
      technology is stressed. The results of this study can form a base for the
      standardization of Nigerian diets based on these legumes.

PMID- 8882369
TI  - Effect of sesame seed proteins supplementation on the nutritional, physical,
      chemical and sensory properties of wheat flour bread.
AB  - Sesame products (sesame meal, roasted and autoclaved sesame meal, sesame protein
      isolate and concentrate) were added to Red wheat flour to produce blends at
      protein levels of 14, 16, 18 and 20 percent. Dough properties were studied using
      a Brabender Farinograph. Loaves were prepared from the various blends using the
      straight dough procedure and then evaluated for volume, crust and crumb colour,
      crumb texture, flavour and overall quality. The water absorption, development
      time and dough weakening were increased (p < 0.05) as the protein level increased
      in all blends; however, dough stability decreased. Sesame products could be added
      to wheat flour up to 18 percent protein level (sesame protein isolate) and up to
      16 percent protein level (other sesame products) without any observed detrimental
      effect on bread sensory properties. No significant differences (p > 0.05) were
      recorded in loaf volume between control and breads containing sesame protein
      isolate (up to 18 percent protein level) and either autoclaved sesame meal or
      sesame protein concentrate (up to 14 percent protein level). Addition of sesame
      products increased the content not only of protein but also minerals and total
      essential amino acids, especially lysine. The addition also improved in-vitro
      protein digestibility.

PMID- 8882370
TI  - Content of starch and sugars and in vitro digestion of starch by alpha-amylase in
      five minor millets.
AB  - Five varieties of minor millets were studied for their amylose, soluble amylose,
      amylopectin, soluble amylopectin, reducing sugar, total sugar and starch
      contents. Pure starch was isolated from each variety and the enzymic degradation
      of starch by porcine pancreatic alpha-amylase were examined with and without
      gelatinisation. Gelatinised sample of Echinochloa frumentacea (var. K2) showed
      minimal hydrolysis and gelatinised sample of Panicum miliaceum (var. CO3) showed
      maximum hydrolysis of starch by porcine pancreatic alpha-amylase. Gelatinised
      starch was highly susceptible to enzymic digestion when compared to ungelatinised
      starch. The extent of starch degradation varied from 71 to 85 percent in
      gelatinised samples and starch degradation in ungelatinised sample varied from 10
      to 18 percent.

PMID- 8882371
TI  - Effect of traditional processing of cassava on the cyanide content of gari and
      cassava flour.
AB  - Detoxification of cassava cultivars (30572 TMS and 30555 TMS) during their
      traditional methods of processing to produce gari and cassava flour has been
      investigated. The HCN quantitative determination was done using the enzymatic
      assay. Fermentation of cassava pulp for 96 hours during cassava processing for
      gari reduced the HCN by 22 ppm (52.4 percent) and 20 ppm (57.3 percent) for 30572
      TMS and 30555 TMS respectively. There was no significant difference (P > 0.05) in
      the HCN content of the two cultivars. Soaking of the sliced cassava tissue for 24
      hours in cassava flour production prior to sundrying resulted in 16 ppm (38.1
      percent) and 15 ppm (38.4 percent) HCN reduction for 30572 TMS and 30555 TMS
      respectively. HCN loss during sundrying was 6 ppm (14.3 percent) and 5 ppm (12.8
      percent) for the two cultivars. There was significantly (P < 0.05) higher HCN
      loss in processing of gari than cassava flour. The residual cyanide in gari was
      12 ppm for 30572 TMS and 10 ppm for 30555 TMS and that in the flour was 20 ppm
      for 30572 and 19 ppm for 30555 TMS.

PMID- 8882372
TI  - Chemical composition of indigenous wild herbs, spices, fruits, nuts and leafy
      vegetables used as food.
AB  - Thirty wild fruits, nuts, herbs, spices and leafy vegetables were characterized
      and their chemical composition determined. Some of them were not only used for
      food, but for medicine in minor aliments by the natives. Results of the proximate
      analysis showed that on dry weight basis, the crude protein content ranged from
      4.6 to 22.1 percent for spices and herbs, 3.2 to 43.1 percent for fruits and
      nuts, and 15.9 to 35.7 percent for leafy vegetables. The fat (ether extract)
      ranged from 7.5 to 36.0 percent for spices and herbs, 1.8 to 72.6 percent for
      fruits and nuts and 10.6 to 22.6 percent for leafy vegetables. Total carbohydrate
      content ranged from 34.6 to 71.9 percent for spices and herbs, 11.3 to 76.1
      percent for fruits and nuts, and 24.6 to 51.4 percent for leafy vegetables. The
      wild fruits, nuts and leafy vegetables are high in ascorbic acid (Vitamin C.)
      Ascorbic acid content ranged from 18 mg/100 g dry sample to 113 mg/100 g sample
      for fruits and nuts, and 23 mg/100 g to 232 mg/100 g sample for leafy vegetables.
      The levels for peroxide value and free fatty acids (as percent oleic acid) of the
      spices are generally low indicating good storage stability of these plant
      materials. The flavour imparting essential oils (as percent oleoresin) content of
      the spices/herbs were fairly high and ranged from 0.1 to 5.2 percent.

PMID- 8882373
TI  - Effects of soaking, cooking and fermentation on composition, in-vitro starch
      digestibility and nutritive value of common beans.
AB  - A common bean variety, grown in Burundi, was either fermented, soaked and/or
      cooked, and then assessed for nutrient composition, in-vitro starch digestibility
      and protein nutritive value. A decrease in ash, most minerals, vitamins, and some
      essential amino acids was noted for soaked, cooked and soaked-cooked beans.
      Compared to untreated beans, soaking decreased soluble sugar (9.8 percent) but
      increased starch (7.3 percent) and soluble fiber (16.9 percent). In cooked beans,
      an increase in soluble sugar (1.5 percent), and a decrease in thiamine (81.7
      percent), starch (24.6 percent) and soluble fiber (16.6 percent) and nitrogen
      (2.9 percent) contents were observed. Crude fiber (6.9 percent) and starch (10.0
      percent) increased while fat (17.6 percent), fatty acids (linoleic: 10.7 percent;
      linolenic: 14.3 percent) and soluble sugars (25.4 percent) and nitrogen (14.4
      percent) decreased in soaked-cooked beans. Fermentation increased potassium (11.6
      percent), soluble fiber (18.9 percent), and some amino acids but decreased fatty
      acids (linoleic: 13.5 percent; linolenic: 19.9 percent), soluble sugar (75.2
      percent) and vitamin (riboflavin: 41.0 percent; niacin: 24.5 percent) contents in
      common beans. However, the in-vitro starch digestibility was greatly improved
      (12.3 percent) by cooking while it decreased in soaked beans (29.2 percent).
      Soaking-cooking and fermentation did not have any significant effect on the
      digestibility of common bean starch. Finally, among the five treatments applied
      to common beans, only fermentation showed a significant improvement (8.3 percent)
      on the protein nutritive value of this legume.

PMID- 8882375
TI  - New hepatitis A vaccines and their role in prevention.
AB  - The hepatitis A virus (HAV) accounts for 20 to 25% of clinically apparent
      hepatitis cases worldwide. It generally causes mild to moderately severe acute
      illness. The serological prevalence of this virus is high in underdeveloped
      countries where poor sanitary conditions facilitate the spread of the virus. The
      Sentinel Counties studies of the Centers for Disease Control in the US have
      identified a number of factors associated with the acquisition of HAV, including
      household members, homosexual men, children and caretakers in day-care facilities
      who come into contact with individuals who are incubating or in the early phases
      of HAV infection. Poor sanitary conditions, international travel and intravenous
      drug use promote the transmission of the virus. However, in 40% of cases, no risk
      factor can be identified. Immune globulin (IG), once used exclusively for the
      prevention of HAV infection, acts by provoking passive-active immunity. It
      prevents clinical disease but permits subclinical disease to develop.
      Unfortunately, IG provides protection for only 3 to 6 months, necessitating
      repeat inoculation for exposure extending over 180 days. More recently, a number
      of live-attenuated and formalin-inactivated HAV vaccines have been developed and
      studied. The vaccines are well tolerated and highly immunogenic, with only mild
      local adverse reactions. The suggested dose and schedule is 720 ELISA units of
      inactivated vaccine injected intramuscularly at 0, 1 and 6 months. A single
      intramuscular dose of 1440 ELISA units followed 6 to 12 months later by a further
      injection has also been approved by the FDA and is available in several European
      countries. 90% of vaccines achieve protective levels of anti-HAV after the first
      injection. Routine use of the HAV vaccine for pre-exposure prophylaxis is
      expected to replace IG in healthy adults travelling to endemic areas, children in
      day-care centres, military personnel, homosexual men, healthcare workers and
      residents in institutions for the mentally disabled.

PMID- 8882374
TI  - Novel drugs and current therapeutic approaches in the treatment of heart failure.
AB  - Treatment of heart failure attempts to reduce symptoms, increase functional
      capacity and prolong survival. Optimal therapy usually requires a combination of
      several drugs. At present, ACE inhibitors are the drugs of first choice, but must
      be combined with diuretics in symptomatic patients. Digitalis glycosides are
      still an important supplement to diuretics and ACE inhibitors. Specific
      angiotensin receptor antagonists such as losartan have an effect comparable with
      that of ACE inhibitors and may possess certain advantages because of their direct
      effect at the receptor level. Extensive research has been conducted in the
      treatment of heart failure. Newer direct acting vasodilators such as flosequinan
      and epoprostenol have demonstrated improved exercise tolerance but have an
      adverse effect on mortality. Positive inotropic agents consisting of a
      heterogeneous group of drugs have been evaluated. Although novel agents such as
      xamoterol, milrinone, pimobendan and vesnarinone have demonstrated improved
      haemodynamics and improved symptoms, they are not advisable at present due to
      increased mortality related to treatment or a high incidence of adverse events.
      beta-Blockers, used judiciously, may improve functional capacity as well as
      mortality and may be an important supplement to current conventional treatment.
      The new generation of beta-blockers with vasodilating properties such as
      carvedilol and bucindolol appear promising.

PMID- 8882376
TI  - Long term treatment of bipolar disorder.
AB  - Bipolar disorder is characterised by recurrent episodes of mania and depression.
      The major objective of long term treatment is to reduce the frequency of these
      episodes. Lithium is the most widely recommended drug for this purpose, having
      been shown in controlled clinical trials to be more effective than placebo in
      reducing the likelihood of relapse. Unfortunately, its effectiveness in clinical
      practice is less than that predicted from these trials. A major cause of relapse
      is noncompliance, largely due to intolerance to adverse effects such as perceived
      mental sluggishness, thirst, polyuria and weight gain. Regular monitoring of
      lithium plasma concentrations is required to ensure that the range of 0.5 to 0.9
      mmol/L is not exceeded. Concentrations above this can lead to toxic symptoms,
      which if unchecked can cause brain damage and even death. The anticonvulsant
      drugs carbamazepine and valproic acid (sodium valproate) are potential
      alternatives to lithium. Patients who relapse frequently despite lithium may
      benefit from the addition of one of these agents, although formal clinical trial
      evidence of the efficacy of such combination treatment is lacking.
      Antipsychotics, administered as a depot formulation, can reduce the likelihood of
      relapse in patients with frequent manic episodes, especially if associated with
      poor compliance. Psychological treatment and patient education have been shown to
      improve outcome, and should be made more widely available to all patients with
      bipolar disorder.

PMID- 8882377
TI  - Causes and treatment of bone pain of malignant origin.
AB  - Pain relief has been one of the oldest and most important duties of the
      physician. There has been little change with regard to this obligation of all
      caregivers. One-third of patients with advanced cancer will develop clinically
      relevant skeletal metastases and chronic pain during the course of their disease.
      All physicians involved in the treatment of cancer patients should know the basic
      principles of pain treatment. These are described in the following article with
      special regard to bone pain of malignant origin. Correct assessment of pain
      intensity and frequency, as well as of the probable causes of pain, and the
      administration of adequate analgesic treatment should achieve satisfactory
      results in the vast majority of patients. Every physician should obtain detailed
      knowledge of the indications and adequate administration of pain-killing therapy
      as well as possible adverse effects and their successful treatment. It is
      important in particular to concentrate on a few nonsteroidal anti-inflammatory
      drugs (NSAIDs) as well as opiates. Knowledge of adequate doses, maximal
      recommended daily doses, pharmacological properties, important adverse effects
      and interactions is essential for success in the daily routine. Only by selecting
      2 or 3 drugs from each step in the analgesic ladder (WHO) will the nonspecialised
      physician obtain sufficient experience for optimal analgesia. Physicians should
      also not hesitate to contact other specialists (medical oncologists,
      radiotherapists, neurosurgeons, anaesthesiologists and others) in order to
      maximise benefit for an individual patient.

PMID- 8882378
TI  - Diagnosis and treatment of epilepsy in children and adolescents.
AB  - Seizures have a variety of aetiologies and may have various manifestations. Some
      are recurrent and represent the different types of epilepsy, whereas others are
      isolated events. Descriptions of various epileptic seizures, as well as their
      corresponding electroencephalograms (EEGs), have recently led to a unifying
      international classification of epileptic seizures and epilepsy syndromes. These
      classifications are extremely important for the practitioner working with the
      paediatric patient, as they allow for optimal evaluation and treatment. This
      article reviews the epilepsies and epilepsy syndromes with special attention to
      age of onset and prognosis. Special circumstances such as status epilepticus,
      which represents a true medical emergency, are reviewed. The first step in the
      pharmacological management of seizures is to establish the diagnosis of epilepsy.
      The recurrence of seizures (or the risk), seizure type and specific syndrome help
      guide initial treatment choices. There is no drug of choice, but some drugs have
      proven more effective for certain types of seizure. Monotherapy is preferable,
      and combination therapy should only be used if monotherapy with first-line drugs
      fails. Candidates for the newer antiepileptic drugs (e.g. felbamate, gabapentin,
      lamotrigine and vigabatrin) include patients resistant to older agents or who are
      unable to tolerate them. The exact place in therapy of these newer agents is
      uncertain, but in many patients they provide better seizure control and are
      better tolerated.

PMID- 8882379
TI  - Drug treatment of asthma in the elderly.
AB  - Asthma is a chronic inflammatory disease of the airways that may affect
      individuals at any age, and can be especially challenging to diagnose and treat
      in the elderly. The hallmarks of asthma--bronchial hyperreactivity and reversible
      airflow obstruction--lead to symptoms of intermittent wheezing, dyspnoea and
      cough. Occasionally, atypical symptoms such as chest pain or tightness occur and
      may mimic other diseases more common in the elderly, such as ischaemic heart
      disease. It is therefore important to use objective measures such as spirometry
      or bronchoprovocation testing to make a diagnosis. In recent years, trends in the
      treatment of asthma have changed from reliance on shorter-acting bronchodilating
      drugs to long term preventative therapy with inhaled corticosteroids. In some
      elderly asthmatic patients, symptoms may be mild and intermittent, and treatment
      with an inhaled beta 2-adrenergic agent may be all that is required. Most,
      however, experience persistent symptoms, and pharmacological therapy should begin
      with daily inhaled corticosteroids and be increased in a stepwise fashion
      according to the patient's needs. In such patients, short-acting beta 2-agonists
      should be continued as needed for acute symptomatic relief. Longer-acting beta 2
      agonists, oral theophylline and inhaled anticholinergic therapy may be useful.
      When symptoms are more severe and potentially life-threatening, oral
      corticosteroids should be given. Since elderly patients are more likely to
      develop complications of asthma therapy and more likely to manifest adverse
      interactions with other therapeutic agents, more intense monitoring of asthma
      treatment is required in dealing with this population.

PMID- 8882380
TI  - Meloxicam.
AB  - Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) developed for the
      treatment of rheumatoid arthritis and osteoarthritis. It has greater in vitro and
      in vivo inhibitory action against the inducible isoform of cyclo-oxygenase (COX
      2), which is implicated in the inflammatory response, than against the
      constitutive form of this enzyme (COX-1), inhibition of which is associated with
      gastric, renal and other adverse effects. It has anti-inflammatory effects
      similar to or better than those of other NSAIDs in animal models, and a greater
      therapeutic ratio (ulcerogenic potential:efficacy in adjuvant arthritis). In
      healthy volunteers meloxicam 7.5 or 15 mg caused less gastrointestinal mucosal
      damage on endoscopy than piroxicam 20 mg, with a significant difference between
      meloxicam 7.5 mg and piroxicam. In comparative clinical trials, meloxicam was at
      least as effective as piroxicam and naproxen in patients with rheumatoid
      arthritis, and diclofenac and piroxicam in patients with osteoarthritis.
      Meloxicam was at least as well tolerated as piroxicam, diclofenac or naproxen
      overall but had improved gastrointestinal tolerability compared with these
      agents.

PMID- 8882381
TI  - Fluvastatin: a review of its pharmacology and use in the management of
      hypercholesterolaemia.
AB  - Fluvastatin, a member of the group of drugs known as HMG-CoA reductase
      inhibitors, is used in the treatment of patients with hypercholesterolaemia. In
      clinical trials in patients with primary hypercholesterolaemia, fluvastatin 20 or
      40 mg/day achieved marked reductions from baseline in serum levels of low density
      lipoprotein (LDL)-cholesterol (19 to 31%) and total cholesterol (15 to 21%),
      along with modest declines in serum triglyceride levels (1 to 12%) and small
      increases in high density lipoprotein (HDL)-cholesterol levels (2 to 10%). These
      beneficial effects on the serum lipid profile were similar to those demonstrated
      with other HMG-CoA reductase inhibitors, although direct comparative trials are
      limited. Concomitant administration of fluvastatin plus another lipid-lowering
      agent, such as a bile acid sequestrant, a fibrate or nicotinic acid, usually
      reduced serum levels of total cholesterol and LDL-cholesterol by at least a
      further 5 to 10% from baseline compared with fluvastatin monotherapy. Fluvastatin
      has a similar tolerability profile to that of other HMG-CoA reductase inhibitors.
      Gastrointestinal disturbances, which are usually mild and transient, were the
      most frequently reported adverse events with fluvastatin in clinical trials.
      Persistent elevation of serum transaminase levels occurred in approximately 1% of
      fluvastatin recipients, which is similar to the rate for other HMG-CoA reductase
      inhibitors. Unlike other HMG-CoA reductase inhibitors, which have been
      infrequently associated with myopathy and rarely with rhabdomyolysis, these
      events have not been associated with fluvastatin to date, although fluvastatin
      has not been used as extensively as agents such as lovastatin. HMG-CoA reductase
      inhibitors other than fluvastatin, when given in combination with drugs such as
      fibrates, nicotinic acid, cyclosporin or erythromycin, can increase the risk of
      these potentially serious adverse events. Thus far, myopathy or rhabdomyolysis
      have not been reported among patients receiving fluvastatin concomitantly with
      any of these drugs. Therefore, fluvastatin can be given with caution in
      combination with fibrates, nicotinic acid, cyclosporin or erythromycin. In
      conclusion, fluvastatin has similar efficacy and tolerability profiles to other
      HMG-CoA reductase inhibitors, which are among the most effective agents available
      for treating patients with hypercholesterolaemia. Pharmacoeconomic studies
      performed to date suggest an advantage for fluvastatin over other HMG-CoA
      reductase inhibitors, predominantly because of its relatively low acquisition
      costs (at least in those countries in which the evaluations were conducted).
      Thus, fluvastatin is effective and well tolerated in patients with
      hypercholesterolaemia and appears to have an economic advantage over other HMG
      CoA reductase inhibitors, primarily as a result of its relatively low acquisition
      costs.

PMID- 8882382
TI  - Pantoprazole. A review of its pharmacological properties and therapeutic use in
      acid-related disorders.
AB  - Pantoprazole is an irreversible proton pump inhibitor which, at the therapeutic
      dose of 40mg, effectively reduces gastric acid secretion. In controlled clinical
      trials, pantoprazole (40mg once daily) has proved superior to ranitidine (300mg
      once daily or 150mg twice daily) and equivalent to omeprazole (20mg once daily)
      in the short term (< or = 8 weeks) treatment of acute peptic ulcer and reflux
      oesophagitis. Gastric and duodenal ulcer healing proceeded significantly faster
      with pantoprazole than with ranitidine, and at similar rates with pantoprazole
      and omeprazole. The time course of gastric ulcer pain relief was similar with
      pantoprazole, ranitidine and omeprazole, whereas duodenal ulcer pain was
      alleviated more rapidly with pantoprazole than ranitidine. Pantoprazole (40mg
      once daily) showed superior efficacy to famotidine (40mg once daily) in ulcer
      healing and pain relief after 2 weeks in patients with duodenal ulcer in a large
      multicentre nonblinded study. In mild to moderate acute reflux oesophagitis,
      significantly greater healing was obtained with pantoprazole than with ranitidine
      and famotidine, whereas similar healing rates were seen with pantoprazole and
      omeprazole. Pantoprazole showed a significant advantage over ranitidine in
      relieving symptoms of heartburn and acid regurgitation. Reflux symptoms were
      similarly alleviated by pantoprazole and omeprazole. Preliminary results indicate
      that triple therapy with pantoprazole, clarithromycin and either metronidazole or
      tinidazole is effective in the treatment of Helicobacter pylori-associated
      disease; however, these findings require confirmation in large well-controlled
      studies. Pantoprazole appears to be well tolerated during short term oral
      administration, with diarrhoea (1.5%), headache (1.3%), dizziness (0.7%),
      pruritus (0.5%) and skin rash (0.4%) representing the most frequent adverse
      events. The drug has lower affinity than omeprazole or lansoprazole for hepatic
      cytochrome P450 and shows no clinically relevant pharmacokinetic or
      pharmacodynamic interactions at therapeutic doses with a wide range of drug
      substrates for this isoenzyme system. In conclusion, pantoprazole is superior to
      ranitidine and as effective as omeprazole in the short term treatment of peptic
      ulcer and reflux oesophagitis, has shown efficacy when combined with
      antibacterial agents in H. pylori eradication, is apparently well tolerated and
      offers the potential advantage of minimal risk of drug interaction.

PMID- 8882383
TI  - Azithromycin. A review of its pharmacological properties and use as 3-day therapy
      in respiratory tract infections.
AB  - The azalide antibacterial agent azithromycin is a semisynthetic acid-stable
      erythromycin derivative with an expanded spectrum of activity and improved tissue
      pharmacokinetic characteristics relative to erythromycin. The drug is noted for
      its activity against some Gram-negative organisms associated with respiratory
      tract infections, particularly Haemophilus influenzae. Azithromycin has similar
      activity to other macrolides against Streptococcus pneumoniae and Moraxella
      catarrhalis, and is active against atypical pathogens such as Legionella
      pneumophila, Chlamydia pneumoniae and Mycoplasma pneumoniae. Once-daily
      administration of azithromycin is made possible by the long elimination half-life
      of the drug from tissue. Azithromycin is rapidly and highly concentrated in a
      number of cell types after absorption, including leucocytes, monocytes and
      macrophages. It undergoes extensive distribution into tissue, from where it is
      subsequently eliminated slowly. A 3-day oral regimen of once-daily azithromycin
      has been shown to be as effective as 5- to 10-day courses of other more
      frequently administered antibacterial agents [such as erythromycin, amoxicillin
      clavulanic acid and phenoxymethylpenicillin (penicillin V)] in patients with
      acute exacerbations of chronic bronchitis, pneumonia, sinusitis, pharyngitis,
      tonsillitis and otitis media. Adverse effects of azithromycin are mainly
      gastrointestinal in nature and occur less frequently than with erythromycin.
      Azithromycin is likely to prove most useful as a 3-day regimen in the empirical
      management of respiratory tract infections in the community. Its ease of
      administration and 3-day duration of therapy, together with its good
      gastrointestinal tolerability, should optimise patient compliance (the highest
      level of which is achieved with once-daily regimens). Azithromycin is also likely
      to be useful in the hospital setting, particularly for outpatients and for those
      unable to tolerate erythromycin.

PMID- 8882384
TI  - Cytotoxicity of polyamines to Amoeba proteus: role of polyamine oxidase.
AB  - It has been shown that oxidation of polyamines by polyamine oxidases can produce
      toxic compounds (H2O2, aldehydes, ammonia) and that the polyamine oxidase
      polyamine system is implicated, in vitro, in the death of several parasites.
      Using Amoeba proteus as an in vitro model, we studied the cytotoxicity to these
      cells of spermine, spermidine, their acetyl derivatives, and their hypothetical
      precursors. Spermine and N1-acetylspermine were more toxic than emetine, an
      amoebicidal reference drug. Spermine presented a short-term toxicity, but a 48-h
      contact time was necessary for the high toxicity of spermidine. The uptake by
      Amoeba cells of the different polyamines tested was demonstrated. On the other
      hand, a high polyamine oxidase activity was identified in Amoeba proteus crude
      extract. Spermine (theoretical 100%) and N1-acetylspermine (64%) were the best
      substrates at pH 9.5, while spermidine, its acetyl derivatives, and putrescine
      were very poorly oxidized by this enzyme (3-20%). Spermine oxidase activity was
      inhibited by phenylhydrazine (nil) and isoniazid (approximately 50%). Mepacrine
      did not inhibit the enzyme activity at pH 8. Neither monoamine nor diamine
      oxidase activity (approximately 10%) was found. It must be emphasized that
      spermine, the best enzyme substrate, is the most toxic polyamine. This finding
      suggests that knowledge of polyamine oxidase specificity can be used to modulate
      the cytotoxicity of polyamine derivatives. Amoeba proteus was revealed as a
      simple model for investigation of the connection between cytotoxicity and enzyme
      activity.

PMID- 8882385
TI  - Evaluation of mutagenic and cytotoxic effects of sodium fluoride on mammalian
      cells influenced by an acid environment.
AB  - The mutagenic activity of sodium fluoride at reduced pH was studied in the
      V79/HGPRT system. Statistical analysis of the results of mutagenicity testing
      suggests that, despite its high toxicity, sodium fluoride has no mutagenic
      effects at reduced pH on hamster V79 cells. Short-term treatment of cells with
      sodium fluoride at reduced pH inhibits growth activity of cells as well as
      synthesis of pulse-labeled nascent DNA and cumulative RNA synthesis and
      proteosynthesis. From the results of this study we suggest that an acid
      environment which supports formation of hydrogen fluoride increases toxic but not
      mutagenic potencies of sodium fluoride.

PMID- 8882387
TI  - The differential effects of cadmium exposure on the growth and survival of
      primary and established cells from fish and mammals.
AB  - The differential cytotoxic effects of cadmium on fish and mammalian epithelial
      cells in established and primary culture were assessed by looking at the
      reduction of the colony-forming ability and reduction in the extent of growth.
      The influence of medium composition on the toxicity of cadmium was also studied
      using serum-free and serum-containing media. The experiments using immortalized
      cell lines showed that mammalian cells were more sensitive than fish cells to
      cadmium. Both cell types were grown at the same serum concentration. However,
      using the normal primary system, human epithelial tissue explants showed less
      sensitivity to cadmium than did similar cultures from rainbow trout. It is likely
      that cellular mechanisms of cadmium resistance in the different cell types are
      responsible for these effects. As expected, cadmium proved to be more toxic when
      tested in serum-free medium. With fish skin primary cultures, reduction of cell
      numbers was observed at concentrations as low as 5 mumol/L in serum-free medium
      compared to 100 mumol/L in serum-containing medium. This was found to be due to
      the reduction in the activity of free cadmium ions, caused by the presence of
      serum in the medium. It is concluded that serum-free formulations are probably
      preferable when testing pollutants in vitro. The results highlight the importance
      of establishing species-specific pollution tests and standardizing variables. In
      summary, the results show species and culture media differences in cadmium
      toxicity and suggest that caution is required when extrapolating results for
      pollutant effects from one in vitro system to another.

PMID- 8882386
TI  - Assay of free-radical toxicity and antioxidant effect on the Hep 3B cell line: a
      test survey using lindane.
AB  - The content of reduced glutathione and of glutathione disulfide as well as the
      activities of glutathione reductase, glutathione peroxidase, glutathione S
      transferases, catalase and superoxide dismutases were determined in human
      hepatoma Hep 3B cells in relation to free-radical toxicity in order to appreciate
      the defense capacities of these cells compared to data on normal hepatocytes.
      When Hep 3B cells were exposed to lindane, a known inducer of free-radical
      production, superoxide dismutase activity appeared as the best-adapted cellular
      parameter for early detection of the resulting free-radical toxicity.

PMID- 8882389
TI  - Monosomy 6q1: syndrome delineation.
AB  - We report on a girl with a de novo 6q1 interstitial deletion. To our knowledge,
      this is the second reported case with a deletion of 6q11-q15. We review the
      phenotype of monosomy 6q1. Our patient has manifestations similar to others with
      monosomy 6q1 including mental deficiency, growth retardation, short neck, and
      minor facial anomalies.

PMID- 8882390
TI  - Delineation of a clinical syndrome caused by mosaic trisomy 15.
AB  - We report on a boy with mosaic trisomy 15. The clinical manifestations are
      compared with those of the few cases reported up to now. A clinical syndrome is
      delineated consisting of a characteristic shape of the nose and other minor
      craniofacial anomalies, as well as typical deformities of the hands and feet.
      Different degrees of mosaicism may explain the more or less severe manifestations
      in individual patients.

PMID- 8882388
TI  - A cellular model for drug interactions on hematopoiesis: the use of human
      umbilical cord blood progenitors as a model for the study of drug-related
      myelosuppression of normal hematopoiesis.
AB  - A cellular model of hematopoiesis which would be more convenient than bone marrow
      (BM) progenitors and directly relevant to human pathology is needed in order to
      investigate xenobiotic toxicity. Human umbilical cord blood (HCB), previously
      shown to be able to repopulate BM, provides a powerful in vitro model of normal
      human hematopoiesis. In order to validate the use of normal HCB progenitors as
      targets for dose-related myelosuppression, we used clonogenic assays and
      expansion in a liquid culture of progenitor-enriched cell suspensions from HCB. A
      series of 8 reference molecules, doxorubicin, cytosine-arabinoside, 5
      fluorouracil, 3'-azido-3'-deoxythymidine, acetylsalicylic acid, sodium valproate
      and two cephalosporin antibiotics, were tested. In vitro 50% inhibition
      concentrations (IC50) were compared to those observed or reported with BM
      progenitors, and to the values of plasma concentrations from treated patients.
      HCB progenitors as in vitro targets for cytotoxic molecules were easy to access
      and handle, and their use was sensitive, specific and reproducible. They gave
      results similar to BM progenitors and allowed a qualitative approach to cellular
      metabolism and toxicity using morphological, flow cytometric and chromatographic
      methods.

PMID- 8882391
TI  - Recognizing Ullrich-Turner syndrome by discriminant analysis of craniofacial
      structure.
AB  - In the present paper, we propose an efficient strategy for identification of
      craniofacial anomalies in the Ullrich-Turner syndrome (UTS). Standardized
      portrait- and profile-photographs were taken of 21 UTS patients with X-monosomy
      and 21 normal females. Twenty-seven craniofacial parameters were read from the
      photographs. The data were analyzed by discriminant analysis, a multivariate
      statistical method. The result was a function represented by a linear combination
      of all those craniofacial parameters which best separate the two groups. The
      discriminant function was applied to 15 additional patients with UTS of various
      cytogenetic types. All 15 patients were classified correctly. The technique
      facilitates syndrome-recognition and is a contribution toward the study of
      karyotype-phenotype relations.

PMID- 8882392
TI  - Micromegakaryocytes in a patient with partial deletion of the long arm of
      chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura.
AB  - Thrombocytopenia or pancytopenia is frequently reported in patients with partial
      11q deletion but there are no reports on bone marrow morphology of these
      patients. We report on a patient with partial deletion of the long arm of
      chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations
      including chronic thrombocytopenic purpura in whom micromegakaryocytes were found
      in the bone marrow aspirate. This is the first report of the presence of
      micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate
      examination of the bone marrow of other patients with the 11q deletion may
      clarify whether the observation of micromegakaryocytes is common in these
      patients. Micromegakaryocytes may indicate a defect of development. Two genes for
      two DNA binding proteins that are likely to be involved in hematopoiesis map in
      the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear
      factor-related-kB gene that maps to 11q24-q25. It is possible that these genes,
      when present in only one copy, result in thrombocytopenia or pancytopenia as
      observed in this patient.

PMID- 8882393
TI  - Mythos and logos in Hesiod's Theogony, circa 700 B.C.
AB  - Hesiod's Theogony, a completely preserved poem, is dated from about 700 B.C. It
      depicts partly a development, partly a situation that has arisen in the course of
      time in the world. It constitutes an attempt to understand the cosmos as the
      product of a genealogical evolution, which can be seen as a process of successive
      separation, differentiation, and hierarchization. In this attempted picture of
      the world myth and reality are inextricably interwoven. Observations of natural
      phenomena as far as of congenital malformations are accordingly exaggerated and
      undergone mythical transformation. Entities enumerated in this genealogical poem,
      no matter whether they stand for parts and concrete phenomena of the physical
      world or intellectual properties and abstract concepts, behave, think, and act,
      and are accordingly though of, in anthropomorphic terms. Monogamy, polygamy,
      endogamy, exogamy, asexual and sexual reproduction, multiple conceptions and
      births, dominantly and recessively inherited traits, normal and abnormal
      offspring, and perceptions and notions on cosmogony, isogamy, and teratogenesis
      could be observed in the writing of the Theogony and interpreted by rational
      modern concepts.

PMID- 8882394
TI  - Nonimmune fetal hydrops and placentomegaly: diagnosis of familial Wiedemann
      Beckwith syndrome with trisomy 11p15 using FISH.
AB  - We have studied a family in which four members of the same generation were
      affected with Wiedemann-Beckwith syndrome (WBS). Trisomy 11p15 was demonstrated
      using molecular probes in interphase nuclei of formalin-fixed paraffin-embedded
      placenta from a stillborn fetus and in peripheral blood lymphocytes from two
      liveborn female relatives. Clinical examination showed nonimmune hydrops and
      placentomegaly in two siblings and multiple phenotypic abnormalities consistent
      with WBS in the two other relatives. Paternal karyotype of the stillborn infants
      demonstrated a reciprocal translocation (46,XY,t(10;11) (q26;p15)) explaining the
      origin of the extra 11p15 material. This study illustrates the advantages of FISH
      for interphase analysis of chromosome aberrations otherwise not detected even by
      conventional cytogenetic analysis and documents that nonimmune hydrops associated
      with placentomegaly may be the presenting features in familial WBS.

PMID- 8882395
TI  - Hereditary multiple exostoses: confirmation of linkage to chromosomes 8 and 11.
AB  - Hereditary multiple exostoses (EXT) is an autosomal dominant disorder
      characterized by the formation of cartilage capped prominences that develop from
      the epiphyses of the long bones. EXT is heterogeneous with three different
      locations currently identified on chromosomes 8, 11, and 19. Recently, we
      identified and studied 12 large multigenerational EXT families. Linkage analyses
      demonstrates that 6 of these families map to 8q24 and 6 to 11p. None of the
      families map to the chromosome 19 locus. The results suggest that there are two
      major loci, on chromosomes 8 and 11, involved in the cause of EXT. The locus on
      chromosome 19 remains to be confirmed.

PMID- 8882396
TI  - Mild phenotype associated with inv dup 8 (q21.2-q22.3) of maternal origin.
AB  - We report on a girl with a de novo inverted duplication of chromosome 8 (q21.2
      q22.3) associated with a mild phenotype. We were able to establish the maternal
      origin of the rearranged chromosome. We discuss the correlation between genotype
      and phenotype on the basis of a review of the findings from individuals with
      partial dup(8q).

PMID- 8882397
TI  - Variant rhizomelic chondrodysplasia punctata (RCDP) with normal plasma phytanic
      acid: clinico-biochemical delineation of a subtype and complementation studies.
AB  - Rhizomelic chondrodysplasia calcificans punctata (RCDP) is an autosomal recessive
      peroxisomal disorder which affects phytanic acid oxidation and de novo
      biosynthesis of plasmalogens in liver and fibroblasts. Peroxisomal thiolase is
      present in its unprocessed precursor form (44 kDa). We studied a mentally
      retarded 9-year-old girl with cataracts and atypical bone dysplasia. Neurological
      findings were mild compared to classic RCDP. Plasma phytanic acid was normal.
      Results of de novo plasmalogen synthesis and phytanic acid oxidation studied in
      cultured skin fibroblasts were intermediate between normal controls and classic
      RCDP. Peroxisomal thiolase was present only as the unprocessed 44 kDa protein.
      Taken together these results suggest that we are dealing with a variant form of
      RCDP with clinical and biochemical abnormalities much milder as compared to
      classic RCDP. In order to establish the genetic relationship between our patient
      and classic RCDP patients complementation studies were carried out. Earlier
      studies had already shown that fibroblasts from all RCDP patients studied belong
      to a single complementation group. Fibroblasts from our patient could also be
      assigned to this complementation group suggesting that the phenotypic variability
      results from different mutations within the same gene.

PMID- 8882398
TI  - VACTERL with hydrocephalus and branchial arch defects: prenatal, clinical, and
      autopsy findings in two brothers.
AB  - VACTERL association is defined as a combination of vertebral, anal, cardiac,
      tracheoesophageal, renal and limb anomalies, in particular radial defects. In
      recent years hydrocephalus was observed in patients with apparent VACTERL
      association. This particular condition was recognized as a hereditary entity with
      poor prognosis. Both autosomal recessive and X-linked forms were described. Here
      we report prenatal, clinical and autopsy findings in 2 brothers with this
      syndrome, who had, in addition, branchial arch anomalies. The recurrence in this
      family suggests X-linked inheritance. Branchial arch defects have so far not been
      described as part of the VACTERL+H syndrome. This observation further supports
      that a variety of brain anomalies including hydrocephalus associated with VACTERL
      anomalies represents separate entities with a considerable recurrence risk. The
      use of the term VACTERL "association" for these conditions is misleading and is
      discouraged.

PMID- 8882399
TI  - Chorionic villus sampling and transverse digital deficiencies: evidence for
      anatomic and gestational-age specificity of the digital deficiencies in two
      studies.
AB  - Several but not all studies indicate that chorionic villus sampling (CVS) is
      associated with an increased risk for transverse limb deficiencies, including
      digital deficiencies. It has been suggested that variations in results regarding
      the transverse digital deficiencies (TDDs) may be due to the use of different
      classification criteria. We present the combined analysis of two case-control
      studies, the U.S. Multistate CVS (US) study and the Italian Multicentric Birth
      Defects (IP-IMC) study, using two different definitions of TDDs. We compared the
      frequency of CVS exposure in control infants with that among those infants with
      any number of affected digits (any TDD), and those with all five digits of at
      least one limb affected (extensive TDDs). The estimated relative risk (RR) for
      any TDD following CVS was 10.6 (IPIMC) and 6.6 (US). For the extensive TDDs, the
      RR was 30.5 (IPIMC) and 10.7 (US). In both studies, extensive TDDs were less than
      25% of all TDDs. Compared to all TDDs, extensive TDDs were more likely to occur
      after CVS performed earlier in the first trimester (before 10-11 weeks'
      gestation). These findings suggest a relationship between the timing of CVS and
      the severity of TDDs; indicate that using a restrictive definition of TDDs (all
      five digits affected) may limit the ability to evaluate the association between
      CVS and TDDs in populations in whom CVS is usually performed at or after 10
      weeks' gestation; and highlight the necessity to consider gestational age in any
      evaluation of the relative risk for limb deficiencies associated with CVS.

PMID- 8882400
TI  - Reduction of urinary tract and cardiovascular defects by periconceptional
      multivitamin supplementation.
AB  - The objective in the Hungarian randomised double-blind controlled trial was to
      study the preventive effect of periconceptional multivitamin supplementation on
      neural tube-defects and other congenital abnormalities. There were 2,471 and
      2,391 informative offspring (prenatally diagnosed and terminated malformed
      fetuses, stillborn fetuses, and liveborn infants) in the multivitamin and placebo
      like trace element groups, respectively. A single tablet either of a multivitamin
      containing 0.8 mg of folic acid or trace element supplement was given daily for
      at least one month before conception and at least until the date of the second
      missed menstrual period. The total rate of major congenital abnormalities was
      20.6/1,000 in the multivitamin and 40.6/1,000 in the trace element group. After
      the exclusion of six cases of neural-tube defects in the trace element group the
      difference was very highly significant [P = 0.0003; relative risk of 0.54 (95% CI
      0.39, 0.76)]. Multivitamin supplementation appeared to result in a significant
      reduction in the rate of urinary tract abnormalities, mainly obstructive defects,
      and in the rate of sporadic cardiovascular malformations, mainly ventricular
      septal defects. This report is regarded as a hypothesis-generating study
      encouraging others to see if the result can be repeated.

PMID- 8882401
TI  - Craniosynostosis, Philadelphia type: a new autosomal dominant syndrome with
      sagittal craniosynostosis and syndactyly of the fingers and toes.
AB  - The acrocephalosyndactyly syndromes (ACS) are a group of clinically similar
      disorders that share the manifestations of craniosynostosis and a variety of hand
      and foot anomalies. Here we report on a 5-generation kindred segregating sagittal
      craniosynostosis and syndactyly of the fingers and the toes in an autosomal
      dominant manner. The anomalies seen in this kindred comprise a syndrome distinct
      from other craniosynostosis syndromes. For this novel syndrome, we propose the
      name craniosynostosis, Philadelphia type.

PMID- 8882402
TI  - CHILD syndrome in a boy.
AB  - CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb
      defects) occurs, as a rule, exclusively in girls because the underlying X-linked
      gene exerts a lethal effect on male embryos. In this report the characteristic
      manifestations of CHILD syndrome are described in a 2-year-old boy with a normal
      chromosome constitution 46,XY. This exceptional case is best explained by the
      assumption of an early somatic mutation and thus compatible with the concept of X
      linked dominant male-lethal inheritance of this trait.

PMID- 8882403
TI  - Exclusion of linkage between RET and neuronal intestinal dysplasia type B.
AB  - Neuronal Intestinal Dysplasia type B (NID B) is a complex alteration of the
      enteric nervous system belonging to the group of intestinal dysganglionoses which
      may involve rectum, colon, and small intestine. Second only to Hirschsprung
      disease (HSCR), NID B is one of the most frequent causes of chronic constipation
      and pseudo-obstructive intestinal dysmotility. Since NID B is often associated
      with HSCR and point mutations in the RET proto-oncogene have been identified in
      HSCR patients, we analyzed two NID B pedigrees to investigate if RET mutations
      might cause also the NID B phenotype. Linkage analysis demonstrated that the NID
      B locus is not linked to RET in the pedigrees analyzed. Further genetic analyses
      will possibly improve the understanding of the cause and facilitate diagnostic
      procedures in NID B.

PMID- 8882404
TI  - Costello syndrome: update on the original cases and commentary.

PMID- 8882405
TI  - Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide
      binding repertoires of common HLA molecules.
AB  - An HLA-A3-like supertype (minimally comprised of products from the HLA class I
      alleles A3, A11, A31, A*3301, and A*6801) has been defined on the basis of (a)
      structural similarities in the antigen-binding groove, (b) shared main anchor
      peptide-binding motifs, (c) the identification of peptides cross-reacting with
      most or all of these molecules, and (d) the definition of an A3-like supermotif
      that efficiently predicts highly cross-reactive peptides. Detailed secondary
      anchor maps for A3, A11, A31, A*3301, and A*6801 are also described. The biologic
      relevance of the A3-like supertype is indicated by the fact that high frequencies
      of the A3-like supertype alleles are conserved in all major ethnic groups.
      Because A3-like supertype alleles are found in most major HLA evolutionary
      lineages, possibly a reflection of common ancestry, the A3-like supermotif might
      in fact represent a primeval human HLA class I peptide-binding specificity. It is
      also possible that these phenomena might be related to optimal exploitation of
      the peptide specificity by human TAP molecules. The grouping of HLA alleles into
      supertypes on the basis of their overlapping peptide-binding repertoires
      represents an alternative to serologic or phylogenetic classification.

PMID- 8882406
TI  - Isohemagglutinins and xenoreactive antibodies: members of a distinct family of
      natural antibodies.
AB  - Just as anti-blood group A and anti-blood group B antibodies pose a strong
      humoral barrier to the transplantation of allogeneic organs or blood,
      xenoreactive natural antibodies directed against Gal alpha 1-3Gal pose a barrier
      to the transplantation of xenogeneic organs or blood. We tested the idea that,
      although "natural" iso-hemagglutinins and xenoreactive natural antibodies
      recognize distinct structures, they have a similar origin and function. Anti-A
      antibodies, anti-B antibodies, and xenoreactive natural antibodies were present
      in serum at similar concentrations and varied with age, gender, and the
      concentration of total IgM in serum in a similar manner. Anti-A antibodies, anti
      B antibodies, and xenoreactive natural antibodies, unlike some elicited
      antibodies, had a high degree of thermal lability and bound more avidly at lower
      temperatures. The natural antibodies manifest remarkable homogeneity and high
      functional avidity for determinants on a cell surface but only a weak affinity
      for monovalent ligands. These findings suggest that anti-A antibodies, anti-B
      antibodies, and xenoreactive natural antibodies specific for Gal alpha 1-3Gal
      have a common origin and function and, given similar antigen density on target
      cells, provide similar humoral barriers to transplantation or transfusion and
      that these antibodies may be members of a common "family" of antibodies.

PMID- 8882407
TI  - Genetic polymorphisms of the major histocompatibility complex-encoded antigen
      processing genes TAP and LMP in sarcoidosis.
AB  - Sarcoidosis is a granulomatous disease showing a significant increase in the HLA
      DR5, -DR6, and -DR8 associated alleles in Japanese. To investigate whether the
      class I antigen-processing genes, encoded within the MHC class II region between
      the HLA-DP and -DQ loci, are involved in determining the susceptibility to
      sarcoidosis, TAP1, TAP2, and LMP2 alleles were analyzed by the PCR-RFLP method in
      85 Japanese patients with sarcoidosis and 91 healthy controls. There were no
      significant differences in the distribution of TAP1 and LMP2 alleles between the
      subgroups of the patients and controls positive or negative for DR5, DR6, and
      DR8. A significant decrease in the frequency of TAP2*0201 was found among the
      patients negative for DR5, DR6, and DR8 as compared to the DR-matched controls (p
      < 0.05), but this could be explained by its linkage disequilibrium to the
      negatively associated allele DR1. These findings suggest that the TAP or LMP2
      gene is not primarily involved in the susceptibility to sarcoidosis. In the
      course of this study, a linkage disequilibrium was observed in the Japanese
      population between TAP1 and TAP2 alleles, TAP1*0201 and TAP2*0102.

PMID- 8882408
TI  - Substitutions in the HLA-DR alpha chain differentially affect DR7-restricted T
      cell recognition of rabies virus antigen.
AB  - To investigate the functional roles of DR alpha residues in T-cell recognition,
      20 mutants of the DR alpha chain were constructed by site-directed mutagenesis.
      These DR alpha mutants were expressed with WT DR(beta 1*0701) on mouse L cells
      and used as APC for four DR7-restricted T-cell clones specific for rabies virus
      antigens. The results indicate that the DR alpha residues are differentially
      involved in recognition of rabies virus antigen by different T-cell clones.
      Mutations in the floor of the antigen-binding groove (positions 9, 11, 22, and
      24), on the alpha-helix (47, 55, 65, 66, and 72), and surprisingly on the outer
      loop (15, 18, and 19), abrogated recognition by at least one T-cell clone. Most
      of these residues appear to be involved in either peptide or TCR contact, based
      on the DR1 crystal structure. The involvement in T-cell recognition of DR alpha
      residues located in the outer loop outside the binding groove suggests that these
      residues may directly contact TCR, or indirectly contribute to the conformation
      of peptide sitting in the groove.

PMID- 8882409
TI  - Discrimination of HLA-B27 alleles by group-specific amplification followed by
      solid-phase sequencing.
AB  - HLA-B27 is known to be highly associated with ankylosing spondylitis. Until now,
      nine B27 subtypes have been sequenced and may contribute in different fashions to
      ankylosing spondylitis. Additionally, the divergent subtypes may be of clinical
      importance in bone marrow transplantation with alternative donors. The purpose of
      this study was to determine the different subtypes of HLA-B27 by a direct
      sequencing approach. The typing strategy is based on a group-specific
      amplification of the second and third exon followed by automated fluorescence
      sequencing of the polymorphic regions. The extensive sharing of sequence motifs
      between the different B alleles made it impossible to specifically amplify the
      B27 group under the precondition of including all sequence variations necessary
      for a postamplification specificity step. Therefore, for setting up a direct
      sequencing approach of B27, co-amplified B alleles had to be taken into account.
      In order to get unambiguous sequencing chromatograms without any heterozygous
      positions, nested sequencing primers were used which selectively matched sequence
      motifs only present in the second and third exon of the amplified B27 alleles.
      This strategy allowed in all cases investigated a clear separation of the
      haplotypes, revealing unequivocal sequencing results. Using this method, we have
      investigated 93 B27-positive individuals. Sequencing identified the alleles
      B*2702, 2703, 2704, 2705, and 2707. B*2701, 2706, 2708, and 2709 were not
      represented in the population studied.

PMID- 8882410
TI  - DN4: a novel cell surface molecule on cortical epithelial cells of the human
      thymus.
AB  - A novel cell surface molecule, DN4, defined by an mAb raised against human thymic
      epithelial cells, showed a specificity for epithelial cells of the thymic cortex.
      This antigen was not expressed at detectable levels on any other types of tissues
      in the human body except for the thymus and bone marrow. Immunohistochemical
      analysis revealed that the reactivity of anti-DN4 mAb was restricted to the
      thymic cortex, and the antigen-expressing cells were arranged in a reticular
      network with long processes between thymocytes. The cellular nature of DN4
      positive cells was identified as cortical epithelial cells, as DN4 was expressed
      in a subpopulation of freshly prepared thymic stromal cells which contain a large
      amount of keratin and expression of DN4 was strictly confined to the cortical
      area within the thymus on immunohistochemical analysis of frozen tissues.
      Immunofluorescence and flow cytometric analysis revealed that a subpopulation of
      bone marrow cells was also positive for DN4 (20%). The large blasts of normal
      bone marrow cells were clearly labeled with anti-DN4 mAb, in contrast to small
      sized bone marrow cells. This finding suggests that DN4 seems to be transiently
      expressed in certain blastic stages during the differentiation of bone marrow
      cells. Immunoprecipitation of 125I-labeled cell lysates from THP-1 and U937 cell
      lines with anti-DN4 mAb yielded a single chain glycoprotein with an approximate
      size of 80-85 kd. There was a reduction in apparent molecular weight of
      approximately 40 kd in the immunoprecipitation of cell lysates after
      endoglycosidase F treatment. Thus, DN4 seemed to have a considerable amount of
      carbohydrate group. DN4 appears to be a novel cortical epithelial cell antigen of
      the human thymus, and although the role of this molecule has not been well
      established experimentally, the possibility can be suggested that the DN4
      molecule might be involved in the positive selection of thymocytes which occurs
      predominantly in the thymic cortical area.

PMID- 8882411
TI  - Identification of HLA-DR9 (DRB1*0901)-binding peptide motifs using a phage fUSE5
      random peptide library.
AB  - We identified HLA-DRB1*0901-binding peptides by affinity-based selection of a
      phage random peptide library using the biotinylated DR9 complex. Analogue
      peptides with single amino acid residue substitutions of a DR9 binder revealed
      that two major anchors (WxxS, where x is any amino acid) play an essential role
      in binding to DR9. Determination of the binding affinity of synthetic wild-type
      based analogue peptides showed that substituting W to F or L, and S to A, V, or F
      allow high affinity binding with DR9. Collectively, DR9-binding peptide motifs
      identified in this study are characteristic in that (a) only two anchors of the
      NH2-terminal half of binding peptides play important roles in binding, and (b)
      small neutral hydrophilic Ser is allowed as the second anchor for high-affinity
      binding, unlike the other DR-binding motifs heretofore reported. The implications
      of our results are discussed in light of the HLA-DR9-associated susceptibility to
      juvenile-onset myasthenia gravis and systemic lupus erythematosus with
      antiphospholipid syndrome, in particular, T-cell responses to autoantigens.

PMID- 8882412
TI  - No primary association between the 308 polymorphism in the tumor necrosis factor
      alpha promoter region and insulin-dependent diabetes mellitus.
AB  - Whereas TNF-alpha has been implicated in the pathogenesis of IDDM, its possible
      role as a primary genetic susceptibility factor has not been well investigated.
      In this study, we analyzed a biallelic polymorphism in the TNF-alpha promotor
      region in a large collection of IDDM patients and controls ascertained from two
      ethnic populations (U.S. Caucasians and Chinese in Taiwan). We report that the
      associations with TNF-alpha are due to linkage disequilibrium between TNF-alpha
      and the DR3-DQB1*0201 haplotype in both ethnic populations. Our analyses of
      extended haplotypes for the HLA region further substantiate the conclusion that
      no primary association exists between IDDM and the TNF-alpha promoter
      polymorphism.

PMID- 8882413
TI  - The Dai minority population of southwest China: heterogeneity of DR2-associated
      HLA-DRB1,DRB5,DQA1, and DQB1 haplotypes.
AB  - HLA-DR2 is the most common DR specificity (60.3%) identified in the Dai minority
      population of Xishuangbanna, Yunna Province, China. We characterized the DRB1,
      DRB5, DQA1, and DQB1 alleles of 44 unrelated DR2-positive individuals, 11 of whom
      (15%) were DR2 homozygous. Four DRB1 and four DRB5 alleles encoding DR2 were
      identified in this population. The most frequent DR2-associated DRB1 alleles were
      *1602 (gf = 0.164) and *1502 (gf = 0.151). DRB1*1501 (gf = 0.048) and a new
      allele designated DRB1*1504 (gf = 0.014) were also detected, but *1601 and *1503
      were absent. The most frequent DR2-associated DRB5 alleles were *0101 (gf =
      0.233) and *0102 (gf = 0.110). Nine different DR2-associated DR/DQ haplotypes
      were identified. The two most common DR2 haplotypes were DRB1*1602, DRB5*0101,
      DQA1*0102, DQB1*0502 (hf = 0.142) and DRB1*1502, DRB5*0102, DQA1*0101, DQB1*0501
      (hf = 0.075). The new DRB1*1504 allele was found on a single haplotype:
      DRB1*1504, DRB5*0101, DQA1*0102, DQB1*0502 (hf = 0.017). The Dw2, Dw12, Dw21, and
      Dw22 haplotypes, present in many other Asian and Mongoloid populations, were not
      identified in this unique group. However, the Dai minority population is
      characterized by a relatively large number of diverse DR2 haplotypes and a new
      DRB1 allele encoding DR2.

PMID- 8882414
TI  - Description of a novel HLA-B35 (B*3514) allele found in a Mexican family of Nahua
      Aztec descent.
AB  - A new allele, HLA-B*3514, has been found in a Mexican family from Nahua descent.
      Its exon 2 is identical to that of B*3501 allele, but exon 3 bears a 3-base
      difference at codons 152 and 156, which results in Val-->Glu and Leu-->Trp
      changes, respectively, in the corresponding HLA molecule at the peptide-binding
      site. These substitutions may have originated from a DNA stretch donation from an
      allele belonging to the B15 group, enabling HLA-B*3514 to cope with the
      presentation of a new set of antigenic peptides. The high frequency of serologic
      B35 in Amerindians, together with the variety of B35 alleles detected by DNA
      sequencing in these populations, suggest that a frequent B35 subtype was present
      in the founder population and that several B35 subtypes may have been recently
      generated, probably due to the abrupt arrival of new pathogens following European
      invasions.

PMID- 8882415
TI  - T-cell receptor BV6S1 null alleles and HLA-DR1 haplotypes in polyarticular
      outcome juvenile rheumatoid arthritis.
AB  - JRA is a complex of disease subtypes which are normally identified by clinical
      features such as age of onset and extent of joint involvement both at onset and
      during the course of the disease. We previously identified an association between
      TCR BV6S1 null allele and one subgroup of early-onset pauciarticular patients
      positive for HLA-DQA1*0101, an HLA haplotype predisposing to a polyarticular
      course of the disease. In this report we extend this observation by identifying
      an increased prevalence of this nonfunctional or null allele in the patients with
      a polyarticular disease course regardless of the mode of onset. This increase was
      most prominent in clinical subsets that have early onset of the disease and a
      polyarticular outcome. In one clinical group, stratification of patients by the
      HLA allele DQA1*0101 strengthened the association considerably. This implies that
      there is an increased genetic load defined by specific alleles of both MHC and
      TCR genes.

PMID- 8882416
TI  - Abnormalities of lymphocyte subsets in canine systemic lupus erythematosus.
AB  - Canine systemic lupus erythematosus (SLE) is a disease clinically very similar to
      its human counterpart. But so far, no study has reported an accurate evaluation
      of the lymphocyte subsets in the canine disease. Here, we present a study in
      which lymphocyte subsets have been evaluated in the peripheral blood of 20 dogs
      suffering from spontaneous systemic lupus erythematosus (SLE) in active and
      inactive phases, before and during treatment with prednisone and levamisole. 22
      healthy dogs have been used as a control population. We show that canine SLE in
      active phases is associated with a several lymphopenia (1050 +/- 520 10(6)
      cells/l versus 2130 +/- 1 020 10(6) cells/l in controls). A striking finding is
      the imbalance of the CD4 and CD8 subsets (respectively 56.7 +/- 10.7% and 10.9 +/
      3.8% of CD4+ and CD8+ lymphocytes versus 40.5 +/- 11.5% and 18 +/- 4.4% in
      controls) and a strong activation of T-cells in active phases (64.1 +/- 16.9% of
      2B3+ cells versus 46.5 +/- 16.7%). Moreover, we observed a persistence of the T
      subset imbalance during spontaneous evolution. In contrast, the treatment induced
      in dogs showing a good response the correction of CD4/CD8 ratio and no clinical
      manifestations, whereas in low responders no such improvements were observed.
      Thus, this work suggests that the main immunological imbalance seen in SLE could
      be associated with defective suppressor cells and provides further evidence of
      similarity of human and dog SLE.

PMID- 8882418
TI  - Cyclins and autoimmunity: cyclin B1 gene expression and restriction fragment
      length polymorphism in lupus-prone mice.
AB  - Cyclin B1 is the major component of M-phase promoting factor that plays a major
      role in the G2/M transition of cell cycle. We examined the expression of cyclin
      B1 at the protein and mRNA levels in the thymus of 12-week-old autoimmune and
      normal mice. We found an abundance of cyclin B1 protein (58 kDa) in the thymus of
      lupus-prone MRL-lpr/lpr mice, whereas the level of this protein was negligible in
      other strains. The level of the predominant cyclin B1 mRNA (1.7 kb) species was
      not markedly different in these strains, suggesting post transcriptional
      modification of cyclin B1 in the thymus of MRL-lpr/lpr mice. Southern blot
      analysis of cyclin B1 gene showed multiple forms of cyclin B1-related sequences
      in various murine genomes. Flow cytometry showed a significantly higher level of
      cells in the G2/M phase and a significantly lower level in the S phase in
      thymocytes of MRL-lpr/lpr compared to that in normal BALB/c mice, indicating an
      alteration of cell cycle machinery in thymocytes of MRL-lpr/lpr mice. Taken
      together, these data show that an upregulation of cyclin B1 protein and
      accumulation of thymocytes at the G2/M phase in MRL-lpr/lpr mice might play an
      important role in the aberrant development of T cells in these mice.

PMID- 8882417
TI  - Characterization of T cell receptor repertoire and anti-Ro/SSA autoantibodies in
      relation to sialadenitis of NOD mice.
AB  - Non-obese diabetic (NOD) mice develop sialadenitis which morphologically
      resembles the exocrinopathy in human Sjogren's syndrome (SS). The sialadenitis is
      characterized by focal infiltrates of inflammatory cells. Immunoenzyme staining
      (ABC-technique) and monoclonal antibodies defining CD4, CD8, CD11b, TCR
      alpha/beta, gamma/delta, V beta 2, V beta 4, V beta 6, V beta 7, V beta 8.1, 2, V
      beta 10b and V beta 11 were used to examine the infiltrating mononuclear cells
      (MNC) in salivary glands of NOD mice. TCR alpha beta + cells dominated clearly
      over TCR gamma delta + cells in the salivary glands. A predominance of CD4+ T
      cells was identified, while a small population of CD8+ cells was found in the
      salivary gland infiltrates. CD11b+ mononuclear cells were sporadically seen
      within the salivary gland lesions. All different TCR V beta:s which were analysed
      appeared to be utilized at the site of MNC infiltration in salivary glands;
      although with various frequencies. The frequency pattern of V beta gene
      expression in salivary glands was V beta 8.1,2 (15%) > V beta 6 (12%) > V beta 4
      (11%) > V beta 10b (5%) > V beta 11 (5%) = V beta 2 (5%) > V beta 7 (3%).
      Analysis of the TCR V beta utilization in corresponding lymph nodes revealed a
      quite similar frequency pattern as found in the salivary glands. Serum samples
      were also tested for anti-Ro52, Ro60 and anti-La antibodies with Western blot.
      Autoantibody production was limited to anti-Ro/SSA and 3/37 (8%) of the mice were
      found to produce anti-Ro52 kD antibodies. The degree of sialadenitis (focus
      score) appeared not to influence reactivity to the Ro52 kD protein.

PMID- 8882420
TI  - Stress-induced cell surface expression and antigenic alteration of the Ro/SSA
      autoantigen.
AB  - Recent studies have shown that Ro/SSA autoantigen is heterogeneous. There are two
      isoform families; the 60 kD forms (Ro60) and the 52 kD forms (Ro52). Recently we
      have found that autoantibodies to the Ro/SSA proteins are conformation dependent.
      Anti-Ro60 antibodies are mainly directed to the native protein and conversely
      anti-Ro52 antibodies are directed only to the denatured protein. It has been
      known that UV irradiation to cultured keratinocytes induces cell surface
      expression of Ro/SSA and this phenomenon has been thought to be related with
      photosensitivity in patients with anti-Ro/SSA antibodies. We studied the
      quantitative and qualitative changes of the Ro/SSA protein induced by stress,
      such as with heat shock and UV irradiation, and found that only Ro52 could be
      expressed on the cell surface of human peripheral lymphocytes by either heat
      shock or UV irradiation. Moreover, flow cytometric analysis revealed that HS
      treated and UV-treated lymphocytes could be stained with patient sera, and by
      using a technique which combined immunoprecipitation and Western immunoblotting,
      it has been confirmed that Ro52 expressed on the cell surface can be recognized
      by anti-Ro/SSA antibodies in native form while cytoplasmic Ro52 cannot be
      recognized. These data suggest that Ro52 can be antigenic in vivo when expressed
      on the cell surface and may explain the mechanism of direct tissue damage by anti
      Ro/SSA antibodies.

PMID- 8882419
TI  - Genetic and immunological markers of insulin dependent diabetes in Black
      Americans.
AB  - ICA and GAD65 autoantibody profiles and HLA-DR and DQ analysis were performed on
      43 Black juvenile onset IDDM patients and 34 unrelated Black controls from
      Tennessee, USA. 75% of patients were positive for GAD65 autoantibodies but only
      53% had ICA; 39% both ICA and GAD65 antibodies. The strongest HLA association was
      with the DR3 haplotype DRB1*03 DQA1*0501 DQB1*0201 (63% of patients v 12% of
      controls RR = 13.0, p < 0.00002). DRB1*04 DQA1*0301 DQB1*0302, associated with
      IDDM in Caucasians but rare in Negroids, occurred in 27% of patients and 6% of
      controls (RR = 5.9, p < 0.04). All patients carried DQB1*0302 or DQB1*0201.
      DQB1*0602 was significantly reduced in patients (2.4% v 41%, RR = 0.036, p <
      0.008) and DRB1*1501 was absent in patients (0% v 35%). The frequency of GAD65
      autoantibodies in Black American IDDM patients is comparable to that in
      Caucasians; however ICA positivity is reduced. GAD65 antibodies may therefore be
      a more sensitive serological test to identify individuals in the Black American
      general population for markers associated with increased risk of developing IDDM.
      Current screening methods for predicting preclinical IDDM in Caucasians relies on
      a combination of immune and HLA markers of IDDM; studies of these markers in the
      Black Americans will make it possible to extend these options to additional
      genetically diverse populations.

PMID- 8882421
TI  - Anti-ganglioside antibodies in new onset type 1 diabetic patients and high risk
      subjects.
AB  - Insulin dependent (type 1) diabetes mellitus appears to be a genetically
      determined autoimmune disease. Gangliosides have been implicated in type 1
      diabetes as antigenic determinants recognized by islet cell antibodies (ICA) and
      shown to be able to modulate autoimmune phenomena in experimental diabetes. In
      order to explore in type 1 diabetes the humoral immune reactivity against
      gangliosides, taking into account their pancreatic localization and molecular
      characteristics, antibodies to gangliosides GM3, GM2, GM1, GD3, GD1a, GD1b, and
      GT1b have been investigated in sera from new onset type 1 diabetics and relatives
      of type 1 diabetic patients with or without insulin (CIAA) and/or islet cell
      autoantibodies. Using a purposefully designed sensitive ELISA method we found
      that presence of antibodies directed against the pacreatic disialo-ganglioside
      GD3 in a significant percentage of newly diagnosed type 1 diabetics (p < 0.001 vs
      normal controls) but not in CIAA and/or ICA positive relatives of type 1
      diabetics. These findings confirm the involvement of gangliosides in autoimmune
      phenomena related to type 1 diabetes and suggest disialo-ganglioside GD3 as
      target of a humoral immune response associated with the onset of insulin
      dependent diabetes.

PMID- 8882422
TI  - Immunoglobulin gene sequence analysis of anti-cardiolipin and anti-cardiolipin
      idiotype (H3) human monoclonal antibodies.
AB  - Heavy and light chain variable region nucleotide sequences were derived from 6
      human hybridoma antibodies which bear characteristics of antibodies associated
      with the phospholipid antibody syndrome. All antibodies originated from non
      autoimmune individuals and were polyspecific. Four of these reacted with
      cardiolipin (and other antigens) and three carried the H3 idiotype which is
      expressed on a high percentage of disease-associated anti-cardiolipin antibodies.
      This idiotype was localized to the lambda light chain of the H3 monoclonal
      antibody and found on two other antibodies which like H3 expressed V lambda 4 or
      the related V lambda 3 subgroup light chains. The H3 idiotype however did not
      define these subgroups nor was it required or sufficient for anti-cardiolipin
      activity. Anti-cardiolipin binding was found in VH1, VH3 and VH4 heavy chain
      families and in a V kappa 1 light chain. The D region was diverse in both length
      and gene usage. Although all cardiolipin binding antibodies showed little
      deviation from germline variable (V) gene sequences, where mutations occurred
      they tended to be replacement mutations and clustered in complementarity
      determining regions (CDR) suggesting these B cells were derived from antigen
      driven responses. These results from our panel of hybridomas and their comparison
      to other human antibodies provide extensive information on the diversity of
      genetic elements which can be used by cardiolipin-binding antibodies. We also
      show gene sequences which encode the disease-associated H3 idiotype and its
      location on lambda light chains, which imply that some labda light chains may be
      preferentially utilized in auto-reactive hybridomas.

PMID- 8882423
TI  - Different HLA-DQ are positively and negatively associated in Swedish patients
      with myasthenia gravis.
AB  - The aim of this study was to determine the association between HLA-DQ and
      myasthenia gravis (MG) in 79 Swedish patients and 155 unrelated population based
      controls. HLA genotyping was done using polymerase chain reaction combined with
      sequence specific oligonucleotide probes. The DQB allele, DQB1*0201 was
      positively associated with MG, 39/79 (49%) patients and 43/152 (28%) controls (OR
      2.47, Pc = 0.037). DQB1*0201 was observed more frequently in patients with an
      early onset of disease, below 30 years (Pc = 0.033). A negative association was
      found for DQA1*0103, 7/78 (9%) patients and 38/154 (25%) controls (OR 0.30, Pc =
      0.037). DQA1*0501-DQB1*0201 and DQA1*0201-DQB1*0201 together was significantly
      increased in patients when compared to controls (OR 2.68; Pc = 0.019). In
      conclusion, two different DQ2 haplotypes (DQA1*0501-DQB1*0201 and DQA1*0201
      DQB1*0201) were positively and the DQA1*0103 allele was negatively associated
      with MG. Susceptibility and resistance to MG in Swedish patients is mediated by
      HLA-DQ.

PMID- 8882424
TI  - Plakortides, novel cyclic peroxides from the sponge Plakortis halichondrioides:
      activators of cardiac SR-CA(2+)-pumping ATPase.
AB  - As part of a search for novel activators of Ca2+ pumping activity of cardiac SR-
      (sarcoplasmic reticulum), the EtOAc extract of the Jamaican sponge Plakortis
      halichondrioides was shown to be active. Bioassay-guided fractionation of the
      extract followed by preparative TLC and HPLC yielded several known and novel
      compounds. Three of the novel cyclic peroxides, plakortides F, G, and H (3, 4,
      and 5) are the subject of this report. Their structures including relative
      stereochemistry were established by interpretation of spectral data. Micromolar
      concentrations of plakortides F-H (3-5) were found to significantly enhance Ca2+
      uptake by SR.

PMID- 8882425
TI  - Isolation and synthesis of novel farnesyl protein transferase inhibitors,
      valinoctins A and B, from Streptomyces strain MJ858-NF3.
AB  - Two novel farnesyl protein transferase inhibitors, valinoctins A (1) and B (2),
      were isolated from the fermentation broth of Streptomyces strain MJ858-NF3. The
      tentative structures of these compounds were elucidated from NMR and mass spectra
      as dipeptides consisting of valine and a novel amino acyl moiety. Four possible
      isomers of valinoctin A were synthesized, and the protected derivative of the
      appropriate compound was crystallized to give the relative stereochemistry of X
      ray analysis. Since the valine residue of valinoctin A was determined to be the L
      configuration by a chiral HPLC column, absolute configuration of valinoctin A was
      determined.

PMID- 8882426
TI  - Taxol production in nodule cultures of Taxus.
AB  - The in vitro synthesis of secondary compounds from plants is one source of scarce
      and valuable phytopharmaceuticals. Often, some level of cellular or tissue
      differentiation is needed for the biosynthesis of many of these important
      compounds. Nodule cultures, consisting of cohesive multicellular units displaying
      a high degree of differentiation, were initiated from cultured needles of seven
      Taxus cultivars (Taxus cuspidata, Taxus x media 'Hicksii', Taxus x hunnewelliana
      'Richard Horsey', Taxus x media 'Dark Green Spreader', Taxus x media 'L. C.
      Bobbick', and Taxus brevifolia). Under normal semicontinuous perfusion culture
      conditions (bimonthly refreshments to yield 0.2% sucrose), only trace amounts of
      taxol were detected from Taxus nodule cultures. However, with an elevated sucrose
      level (0.5% or 1.0%), taxol production was enhanced in T. cuspidata nodules to
      approximately 12 micrograms taxol/g nodule dry weight (dw). Stimulation of taxol
      production by elevated sucrose levels occurred even in the absence of other
      nutrients. The effect of increased sucrose on taxol induction does not appear to
      be due to an osmotic effect in the medium, suggesting that the increase in taxol
      production may be correlated with a metabolic process within the nodules.
      Although sucrose had a significant effect on taxol production, taxane precursors
      or elicitors of terpenes, as well as other plant secondary metabolites, had no
      effect on the production of taxol from these cultures. In addition to taxol, the
      higher sucrose levels also induced the production of 7-epi-10-deacetyltaxol,
      cephalomannine, and 7-epi-10-deacetylcephalomannine, so that total content of
      these taxanes equaled approximately 39 micrograms taxane/g dw nodules.

PMID- 8882427
TI  - Trichoverroid stereoisomers.
AB  - Trichoverroids, which lie along the biosynthetic path between the simple and the
      macrocyclic trichothecenes, have been characterized previously as sets of
      diastereomers that have the S-configuration at C-6' and are epimeric at C-7'. An
      isolate of Myrothecium verrucaria (ATCC 20540), which is the only species of
      Myrothecium reported to produce the macrocyclic trichothecene isororidin E (3a),
      produces trichoverrols (1) and trichoverrins (2) that are epimeric at C-7' but
      that have R-configurations at the C-6' centers. Also reported are several
      additional naturally occurring C6'R-series trichoverroids that have varied
      structural modifications, including several E,Z-isomers 7-9, 9 beta,10 beta
      epoxides 11a and b, 12,13-deoxyisotrichoverrin B (10), and 8 alpha
      hydroxyisotrichoverrin A (12).

PMID- 8882428
TI  - Ability of different flavonoids to inhibit the procoagulant activity of adherent
      human monocytes.
AB  - Sixty-five natural flavonoids of various chemical classes were screened for their
      ability to inhibit the procoagulant activity of adherent human monocytes
      stimulated by endotoxin and interleukin-1 beta in vitro. Eighteen of these
      compounds inhibited the interleukin-1 beta-induced expression of tissue factor on
      human monocytes, but the most active compound was a biflavonoid: hinokiflavone.

PMID- 8882429
TI  - Cyclic peptides from higher plants. 24.1 yunnanin C, a novel cyclic heptapeptide
      from Stellaria yunnanensis.
AB  - A novel cytotoxic cyclic heptapeptide, yunnanin C (1), was isolated from the
      roots of Stellaria yunnanensis. The structure of 1, cyclo(-Gly-Ile-Gly-Phe-Tyr
      Ser-Pro-), was elucidated from spectroscopic evidence and by chemical
      degradation.

PMID- 8882430
TI  - Bioactive steroidal alkaloids from Solanum umbelliferum.
AB  - Bioassay-directed fractionation of the MeOH extract of Solanum umbelliferum
      afforded solasodine (1), O-acetylsolasodine (2), and solasodine 3-O-beta-D-
      glucopyranoside (3). Alkaloids 1 and 2 exhibited significant activity toward DNA
      repair-deficient yeast mutants, whereas 3 and the synthetic analogues N
      acetylsolasodine (4) and N,O-diacetylsolasodine (5) were found to be inactive.
      Compounds 2 and 3 are new natural products.

PMID- 8882431
TI  - Antineoplastic agents. 340. Isolation and structural elucidation of bryostatins
      16-18.
AB  - Separation of two trace cancer cell growth inhibitory (P388 leukemia) fractions
      from about 1000 kg of wet Gulf of Mexico Bugula neritina (Bryozoa) has led to the
      isolation of bryostatins 16-18 (2-4). A combination of HRFABMS and high-field
      (400 MHz) 1H- and 13C-NMR spectral analyses were employed to assign the
      structures. The three new 20-desoxybryostatins 16 (2), 17 (3), and 18 (4) showed
      significant growth inhibitory activity (P388 ED50, 2, 9.3 x 10(-3) micrograms/mL,
      3, 1.9 x 10(-2) micrograms/mL, and 4, 3.3 x 10(-3) micrograms/mL) against murine
      P388 lymphocytic leukemia.

PMID- 8882432
TI  - A new prenylated flavonol from the root of Petalostemon purpureus.
AB  - A new prenylated flavonol, petalopurpurenol (1), and a known dihydroflavonol,
      petalostemumol (2), have been isolated by DNA scission-guided fractionation of
      the organic portion of a 20% MeOH/CHCl3/H2O partition of a 50% MeOH/CHCl3 extract
      of the roots of Petalostemon purpureus. Compound 2 displayed moderate activity in
      DNA-scission assay. Both compounds 1 and 2 were evaluated for cytotoxicity in a
      panel of human cancer cell lines. The structures of petalopurpurenol (1) and
      petalostemumol (2) were determined by spectroscopic analysis.

PMID- 8882433
TI  - Metabolites from an Antarctic sponge-associated bacterium, Pseudomonas
      aeruginosa.
AB  - In an ongoing survey of the bioactive potential of microorganisms associated with
      marine invertebrates, the culture media of a sponge-associated bacterial strain
      of Pseudomonas aeruginosa was found to contain metabolites which inhibit the
      growth of several Gram-positive microorganisms. A series of diketopiperazines (1
      6) including a new natural product (6) and two known phenazine alkaloid
      antibiotics (7 and 8) were isolated from the culture broth of this bacterium.

PMID- 8882434
TI  - Bioactive ent-kaurene diterpenoids from Annona senegalensis.
AB  - Activity-guided fractionation of the stem bark of Annona senegalensis gave four
      bioactive ent-kaurenoids (1-4). Compound 2 showed selective and significant
      cytotoxicity for MCF-7 (breast cancer) cells (ED50 1.0 microgram/mL), and 3 and 4
      exhibited cytotoxic selectivity for PC-3 (prostate cancer) cells but with weaker
      potencies (ED50 17-18 micrograms/mL). The structure of the new compound, 3, was
      deduced from spectral evidence.

PMID- 8882435
TI  - A novel monogalactosylacylglycerol with inhibitory effect on platelet aggregation
      from the cyanophyceae Oscillatoria rosea.
AB  - (2S)-1-O-Palmitoyl-3-O-beta-D-galactopyranosylglycerol, isolated from the marine
      alga Oscillatoria rosea, inhibited platelet aggregation induced by U46619, a
      thromboxane A2 analogue. Its structure was elucidated by spectroscopic analysis
      and chemical evidence.

PMID- 8882436
TI  - New bioactive cerebrosides from Arisaema amurense.
AB  - From Arisaema amurense, four new cerebrosides were isolated along with a known
      cerebroside. The new cerebrosides were characterized as 1-O-beta-D-glucopyranosyl
      (2S,3R,4E,8Z)-2-[(2(R)- hydroxyicosanoyl)amido]-4,8-octadecadiene-1,3-diol (1),
      1-O-beta-D- glucopyranosyl-(2S,3R,4E,8Z)- 2-[(2-hydroxyoctadecanoyl)amido]-4,8
      octadecadiene-1,3-diol (2), 1-O-beta-D- glucopyranosyl- (2S,3R,4E,8E)-2-[(2
      hydroxyicosanoyl)amido]-4,8-oct adecadiene-1,3-diol (4), and 1-O-beta-D-
      glucopyranosyl-(2S,3R,4E,8E)-2-[(2-hydroxyoctadecanoyl )amido]-4,8- octadecadiene
      1,3-diol (5), respectively. These cerebrosides displayed significant
      antihepatotoxic activity.

PMID- 8882437
TI  - Phytogrowth-inhibitory and antifungal constituents of Helianthella quinquenervis.
AB  - Investigation on the roots of Helianthella quinquenervis (Hook.) A. Gray
      (Asteraceae), led to the isolation of one new benzofuran (6-methoxy-tremetone
      (1)) and a new prenylacetophenone (4-beta-D-(glucopyranosyloxy)-3-[3-methoxy
      trans-isopenten-1 -yl] acetophenone (3)). In addition, 6-hydroxy-3
      methoxytremetone (2), encecalin (6), euparin (5), demethylencecalin (4), and
      angelic acid were obtained. Structural assignments of the isolated compounds were
      based on spectroscopic and spectrometric analysis. Natural products 1-4 showed
      marginal cytotoxicity against three human tumor cell lines [MCF-7, A-549, and HT
      29]. Compounds 4 and 6 inhibited the radicle growth of Amaranthus hypochondriacus
      and Echinochloa crusgalli. Furthermore, substances 4-6 exhibited antifungal
      activity against Trichophyton mentagrophytes.

PMID- 8882438
TI  - Inhibition of hepatitis B surface antigen secretion on human hepatoma cells.
      Components from Rubia cordifolia.
AB  - The antiviral activity in the roots of Rubia cordifolia was examined, and three
      naphthohydroquinones, furomollugin (1), mollugin (2), and rubilactone (3), were
      isolated from it. Compounds 1 and 2 strongly suppressed the secretion of
      hepatitis B surface antigen (HBsAg), both with IC50 = 2.0 micrograms/mL, in human
      hepatoma Hep3B cells while having little effect on the viability of the cells.
      Evaluation of structurally related derivatives of 1 and 2 revealed that a 6
      hydroxy group and a pyran or furan ring contribute to this suppressive effect.

PMID- 8882439
TI  - Intellectual property rights, naturally derived bioactive compounds, and resource
      conservation. Meeting report.
AB  - The first Interim Annual Meeting of the American Society of Pharmacognosy was
      held October 20-22, 1994, in San Jose, Costa Rica. In the symposium, which was
      the main scientific focus of the meeting, speakers from both developed and
      developing countries presented their perspectives on issues regarding
      intellectual property rights in regard to drug development from natural sources,
      conservation of natural habitats, and international conventions on
      bioprospecting. Careful evaluation of existing policies, laws, and conventions;
      sensitivity to the respective world views of prospective partners; equitable
      sharing of benefits including scientific collaboration; and a sense of fairness
      will be necessary to ensure that the genetic resources of all countries will be
      developed for the benefit of humankind.

PMID- 8882440
TI  - [Association of congenital chromosome abnormalities and malignant diseases].
AB  - Chromosome studies were carried out on 112 children with acute leukemia and 10
      children with solid tumor. Acquired chromosome abnormalities were identified
      shown in 52% of patients with hematologic disorders (ALL 40%, ANLL 64%) and in
      four of 10 patients with non-hematologic disorders. Six patients had a
      constitutional chromosome aberration: three of them with ANLL and one child with
      ALL had trisomy 21, an other one with ALL had balanced translocation [t(2;7)] of
      maternal origin, and one child with Wilms' tumor-anirida syndrome had
      del(11)(p13). Two Down syndrome children with ANLL had additional acquired
      karyotypic changes. One of the Down's syndrome patients with ANLL M2 had t(8;21),
      the karyotype of the leukemic cells was: 47, XY, t(8;21) +21c. The other case
      with 21;21 centric fusion had hyperdiploidy, extra chromosomes were: +8, +14,
      +19, +20. It is very important to distinguish acquired and constitutional
      abnormalities in tumor cells.

PMID- 8882441
TI  - [Malignant mesothelioma of the pleura].
AB  - Forty cases of malignant mesothelioma diagnosed from 1989 to 1994 at the
      Department of Pulmonology, Semmelweis Medical School were reviewed
      retrospectively. In 6 patients (15%) had a history of exposure to asbestos. The
      possibility of the malignant mesothelioma was raised by the clinical signs and
      the results of chest X-ray, chest computed tomography and sonography of the chest
      at their patients. Diagnosis was made by hystological examination of
      thoracoscopic or needle pleural biopsy in 15 and 8 cases, respectively, by
      cytological examination of fine needle pleural biopsy or pleural fluid in 7 and 6
      cases, respectively, and by thoracotomy in 5 patients. Diagnosis was confirmed by
      multiple procedures in 11 patients. In six patients, diagnosis of malignant
      mesothelioma was made only by autopsy. The patients were staged according to
      Butchart et al. Longer survival was noted in the patients with earlier stages.
      Single or combined therapeutic modalities such as surgery (in 5 patients),
      chemotherapy (in 10 patients) and radiotherapy (in 3 patients) were used with
      additional symptomatic treatment in the majority of the cases. Pleurodesis also
      was done in 7 cases. There was no difference in survival among patients had
      received different treatment.

PMID- 8882443
TI  - [Organization and operation of special menopause clinics].
AB  - The authors summarized the special background information and practical
      experiences which helped them to organize the menopausal clinics for the patients
      in the peri- and postmenopausal age. The aim of the clinic was to to diagnose and
      manage the oestrogen deprivation in order to provide special care for the
      patients. The authors identified three key player; the general practitioners, the
      menopausal clinics and specialised centers in the field of the menopausal
      medicine. They emphasized the multidisciplinary features of the initial
      assessment and management plan of the hormone replacement therapy, the initiative
      role of the gynaecologist indicating and checking up the hormon replacement
      therapy and also undertaking the yearly oncogynaecologic screening. It was
      summarized the opportunities and limitations of the hormone replacement therapy
      to prevent, decrease or eradicate vasomotor, psychological and organic
      consequences of the menopause. They outlined the indications and
      contraindications and side-effects of the hormone replacement therapy. Finally,
      some theoretical and practical issues of the hormone replacement therapy were
      discussed.

PMID- 8882442
TI  - [Experience with the clinical use of laser surgery in the nasal cavity].
AB  - The authors treated nasal bleedings of various origin, lower turbinate
      hypertrophy, nasal polyps and rhinolithiasis using different, kinds of surgical
      lasers for the first time in Hungary. According to their experiences the modern
      CO2 and Nd-Yag laser with advanced optics are applicable for the purposes of
      endonasal laser surgery. The use of CO2 laser is indicated for vaporization and
      cutting of small haemorrhagic areas without strong bleeding, Nd-Yag laser is more
      suitable for coagulation and vaporization of highly vascularised tissue masses.
      The, fiber optic introducible into the endoscope makes the Nd-Yag laser useful
      for almost every endoscopic nasal and paranasal surgery, making simultaneous
      video-documentation possible. Using lasers combined with endoscopes (in itself or
      as an independent step of operation) is a method with minimal operational stress
      and invasivity, which makes effective surgery possible, in many cases as one-day
      surgery.

PMID- 8882444
TI  - [Successful surgical management of cardiovascular thrombosis and aortic
      coarctation, caused by protein C deficiency, in a newborn infant].
AB  - 10 days old newborn with coarctation of aortae had multiple thrombus formation in
      the left atria and aortic arch. At first step aortic isthmus reconstruction and
      thrombectomy was performed, which were followed by the multiple thrombectomy from
      mitral valve and aortic arch by extracorporeal circulation. Laboratory findings
      showed protein C deficiency. This is the first reported case with multiple
      thrombotic formation caused by protein C deficiency and aortic isthmus stenosis
      successfully operated on.

PMID- 8882445
TI  - [A multivariate analysis approach to antineoplastic and antiviral structure
      activity relationships to a series of podophyllotoxins].
AB  - In this work, the authors have used technics of multivariate analysis to
      determine the structure-activity relationships of 46 podophyllotoxin derivatives
      and analogs studied for their antineoplastic and antiviral activities. The
      obtained results allow to envisage the possible synthesis of more specific
      molecules by making modifications in the structure of the model molecular
      archetype.

PMID- 8882446
TI  - [Immunonephelometric analysis of immunoglobulin light chains: agreement between
      the theoretical and experimental model. Assessment of the reference values of the
      kappa/lambda ratio and the heavy to light chain ratio].
AB  - Since the introduction of fully automated nephelometric systems simultaneous
      measurements of immunoglobulin light chains kappa (kappa) and lambda (lambda) and
      IgG, IgA and IgM have become increasingly used for the routine assessment of
      humoral immunity. From these data two ratios were calculated, the kappa/lambda
      ratio and the heavy chains to light chains ratio. As changes in these ratios
      might have some predictive clinical value besides reflecting a monoclonal
      component, it is necessary to know mean and reference limits of these ratios. On
      account of differences in the calibration method of the light chains measurements
      (either free light chains or light chains bound to a complete molecule) and of
      differences in the calculation method of the heavy chains to light chains ratio
      we were led to conduct our own investigation. IgG, IgA and IgM and kappa and
      lambda light chains were immunonephelometrically measured in the sera of 84 blood
      donors. For each sample theoretical values for kappa + lambda, kappa and lambda,
      and kappa/lambda were calculated using the existing relation between the
      concentration of a given immunoglobulin and the concentration of bound light
      chains. Using the Valtec Protocole and the t test we were able to evidence highly
      significant differences (p < 10(-4) between theoretical and experimental values
      of kappa, lambda and kappa + lambda; those differences could be proved to be
      directly linked to the nephelometric technique itself. However the experimental
      kappa/lambda ratio did not appear to differ from the theoretical one nor the
      standardization method to have an effect on the reference values of this ratio,
      our values (mean and reference limits, 1.81, 1.29-2.53) being very similar to
      previously published results. Concerning the so called heavy chains to light
      chains ratio two methods were used to express it, one consisting in the ratio of
      the theoretical kappa + lambda value to the experimental one with the following
      results, 1.05 and 0.93-1.18 for the mean and reference limits and the other one
      using the raw data. The results were as follows: mean 3.50, reference limits 3.11
      3.94.

PMID- 8882447
TI  - [Migraine and serotonin: mechanisms and treatments].

PMID- 8882448
TI  - Culture temperature affects the molecular motion of bacteriorhodopsin within the
      purple membrane.
AB  - We measured the absorption anisotropies of bacteriorhodopsin (bR) within a purple
      membrane suspension after photo-excitation in the millisecond time range. The
      purple membranes used were isolated from Halobacterium salinarium grown at three
      different culture temperatures, 37.0, 43.0 and 47.5 degrees C. For the membranes
      from the 37.0 degrees C culture, the observed anisotropies at wavelengths of 410,
      570 and 680 nm showed almost the same slow decay. The slow decaying of the
      anisotropies originated from the rotation of the membrane itself. Using the
      membranes from the 43.0 and 47.5 degrees C culture, however, we found that the
      anisotropy change varied at each wavelength measured. In these cases, it is shown
      from detailed data analysis that 1) the rotational motion of photo-intermediates
      within the membrane is more restricted than that of non-excited bR and 2) the
      distorted arrangements of the proteins within the membrane remain, even after
      photo-intermediates return to ground-state bR. This restricted motion is probably
      caused by the conformational changes in photo-intermediates, which prevent the
      rotation of the monomer protein and/or lead photo-intermediates to bind with
      neighboring proteins.

PMID- 8882449
TI  - Medicinal foodstuffs. II. On the bioactive constituents of the tuber of
      Sagittaria trifolia L. (Kuwai, Alismataceae): absolute stereostructures of
      trifoliones A, B, C, and D, sagittariosides a and b, and arabinothalictoside.
AB  - From the medicinal foodstuff "kuwai", the tuber of Sagittaria trifolia L., four
      bioactive diterpene ketones, trifoliones A, B, C, and D, two diterpene
      glucosides, sagittariosides a and b, and a nitroethylphenol glycoside,
      arabinothalictoside, were isolated, together with six known diterpenes. Their
      absolute stereostructures were determined on the basis of chemical and
      physicochemical evidence which included the application of a modified Mosher's
      method and an exciton chirality method. Among the diterpene constituents,
      trifoliones A, B, C, and D exhibited inhibitory effects on the histamine release
      from rat mast cells induced by compound 48/80 and calcium ionophore A-23187.

PMID- 8882450
TI  - Synthesis and affinities for dopamine (D2) and 5-hydroxytryptamine (5-HT2A)
      receptors of 1-(benzoylpropyl)-4-(1-oxocycloalkyl-2-ethyl)-piperazines as cyclic
      butyrophenone derivatives.
AB  - Starting from benzo- or thienocycloalkaneacetic acids, we have prepared a series
      of 1-(3-p-fluorobenzoylpropyl)-4-(1-oxo-benzo- or thienocycloalkyl-2
      ethyl)piperazines 8a-e containing both semirigid and linear butyrophenones
      pharmacophores. The affinities of these compounds for dopamine (D2) and 5
      hydroxytryptamine (5-HT2A) receptors were evaluated in vitro in receptor-binding
      assays and in functional experiments. The ratios of pKi's for 5-HT2A/D2 receptors
      may be useful for rapid screening of new compounds and assessing potential
      induction of extrapyramidal symptoms; ratio values > or = 1.12 (Meltzer's ratio)
      are predictive of an atypical antipsychotic profile. The new molecules had a
      ratio in the range of 0.96-1.11 while haloperidol showed a ratio of 0.93. The 2
      piperazinoethyl thiotetralone derivative 8d (QF 0506B) with a ratio of 1.11 was
      the most active compound.

PMID- 8882451
TI  - Quantitative structure-activity relationships of Ca(2+)-antagonistic semotiadil
      congeners.
AB  - Structure-Ca2+ antagonistic activity relationships of semotiadil (1) congeners
      having a benzothiazine cyclic system were studied quantitatively by the Hansch
      Fujita method. A quadratic dependency of the activity on ClogP, a lipophilic
      descriptor, of terminal arylalkylamine moieties was suggested. A correlation
      between the dipole moment component of the 5'-substituted 2-phenylbenzothiazine
      parts and the potency was also suggested. Additionally, quantitative analysis was
      successfully shown for the 2-substituted 1 congeners. The results gave
      information about the mode of binding of 1 with Ca2+ receptor.

PMID- 8882452
TI  - Synthesis and biological activity of the metabolites of diethyl 4-[(4-bromo-2
      cyanophenyl)carbamoyl]benzylphosphonate (NO-1886).
AB  - Five metabolites of diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate
      (NO-1886) (1) were synthesized to confirm their proposed structures. The
      metabolites (2-6) were found to be identical with the synthesized compounds.
      These metabolites were orally administered to Triton WR-1339-induced
      hypertriglyceridemic rats, and the plasma levels of triglycerides were measured
      to estimate lipoprotein lipase activity. All the metabolites showed lower potency
      than NO-1886.

PMID- 8882453
TI  - Mechanism of inhibition of H+, K(+)-ATPase by sodium 2-[[4-(3- methoxypropoxy)-3
      methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole (E3810).
AB  - Sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl ]- 1H
      benzimidazole (E3810) and omeprazole inhibit gastric acid secretion through
      inhibition of the activity of H+, K(+)-ATPase present in parietal cell membrane
      vesicles, by chemical modification of SH groups in the enzyme molecule. In order
      to clarify the mechanism of the chemical modification, reaction products of E3810
      and omeprazole with 2-mercaptoethanol under acidic conditions (pH 3, 4, 5, 6)
      were isolated by HPLC, and subjected to structural analysis by UV, 1H-NMR and
      mass spectrometry. E3810 and omeprazole appeared to undergo two kinds of
      reactions, affording disulfide-type products (type I reaction) and sulfide-type
      products (type II reaction). The rates of these reactions were determined by
      HPLC, and the stability of the products in the presence and absence of
      glutathione was investigated. In the case of E3810, type I reaction was found to
      proceed faster than type II reaction at every pH value studied. The type I
      reaction of E3810 was faster than that of omeprazole. The rate of type I reaction
      decreased at pH 5 and 6, especially for omeprazole, and the contribution of type
      II reaction increased as the pH of the reaction mixture was increased. The
      sulfide-type modification products were stable, whereas the formation of the
      disulfide-type modification products was reversed by the action of endogenous SH
      compounds such as glutathione. These results suggest that higher inhibitory
      activity of E3810 against gastric acid secretion and faster recovery of the
      enzyme activity after inhibition by E3810 can be expected, as compared with those
      of omeprazole.

PMID- 8882454
TI  - Oral absorption improvement of poorly soluble drug using solid dispersion
      technique.
AB  - A new triazol antifungal agent, (+)-2-(2,4-difluorophenyl)-3-methyl-1-(1H-1, 2,4
      triazol-1-yl)-3-[6-(1H-1,2,4-triazol-1-yl)pyridazin++ +-3-ylthio]butan-2-ol (MFB
      1041), shows poor oral absorption and is practically insoluble in water (1.2
      micrograms/ml). Solid dispersion systems with an enteric polymer such as
      hydroxypropylmethylcellulose phthalate (HP-55) and carboxymethylethylcellulose
      (CMEC), and a nonenteric polymer, hydroxypropylmethylcellulose (Metolose) were
      evaluated to improve drug absorption and solubility. The oral bioavailabilities
      of these solid dispersions in beagle dogs were over 6 times higher than that of a
      suspension system with increasing drug solubility in an alkaline medium. X-Ray
      powder diffraction measurement of the solid dispersion showed a complete drug
      phase change from a crystal to an amorphous state. Further, from the results of a
      stability test, the preparations were stable in a desiccated condition and the
      absorption profiles also showed no change. From the results, it was suggested
      that the oral administrative preparation of MFB-1041 having a superior absorption
      profile and a high stability could be obtained by a drug phase change from a
      crystal to an amorphous state, especially in the spray-drying method using
      enteric polymers.

PMID- 8882455
TI  - Possible enhancing mechanism of the cutaneous permeation of 4-biphenylylacetic
      acid by beta-cyclodextrin derivatives in hydrophilic ointment.
AB  - The enhancing effects of heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta
      CyD) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) on the percutaneous
      absorption of 4-biphenylylacetic acid (BPAA), a nonsteroidal anti-inflammatory
      drug, in hydrophilic ointment were studied and compared with the parent beta
      cyclodextrin (beta-CyD). 13C-NMR measurements suggested that the biphenyl group
      of BPAA is preferably included within the cavity of three beta-CyDs. The three
      beta-CyDs remarkably enhanced the release of BPAA from the hydrophilic ointment
      base and the in vitro cutaneous permeation, depending on the increase in
      solubility of BPAA in the ointment base. Pretreatment of the ointment containing
      DM-beta-CyD or HP-beta-CyD onto the isolated skin of hairless mice, however,
      provided no effects on the skin permeation of BPAA. When propylene glycol was
      used as a vehicle, both the release rate and cutaneous permeation parameters
      showed no appreciable difference between BPAA alone and its HP-beta-CyD complex,
      because the solubilities of BPAA and its HP-beta-CyD complex were almost
      comparable in the vehicle. The present results suggested that the enhancing
      effect of beta-CyDs on the percutaneous absorption of BPAA can be mainly ascribed
      to an increase in the solubility of BPAA in the hydrophilic ointment.

PMID- 8882456
TI  - Studies on metabolites of mycoparasitic fungi. V. Ion-spray ionization mass
      spectrometric analysis of trichokonin-II, a peptaibol mixture obtained from the
      culture broth of Trichoderma koningii.
AB  - The sequence of a peptide, trichokonin-II (TK-II), obtained from the culture
      broth of Trichoderma koningii OUDEMANS, was examined by ion-spray ionization mass
      spectrometry (ISI-MS), including the collision-induced dissociation (CID)
      technique. TK-II was concluded to be a mixture of three peptaibols, TK-IIa, TK
      IIb, and TK-IIc.

PMID- 8882457
TI  - Preparation and antirheumatic activity of optically active 2-acetylthiomethyl-4
      (4-methylphenyl)-4-oxobutanoic acid (KE-298).
AB  - 2-Acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanonic acid (KE-298) is an
      antirheumatic agent. To elucidate the effects of optically active KE-298, we
      resolved the racemic acid and obtained the two optical isomers. (+)-KE-298 was
      converted to the 4-bromobenzyl ester derivative and the absolute structure was
      confirmed as (S) by X-ray crystallographic analysis. The pharmacological
      activities of the optical isomers and racemic KE-298 were compared by using the
      characteristic tests for KE-298. Though (+)-KE-298 showed a stronger suppressive
      effect on rat adjuvant arthritis than (-)-KE-298, no difference between the two
      isomers was detected in in vitro tests (enhancing effect on lymphocyte
      transformation, IL-1 antagonistic effect).

PMID- 8882458
TI  - Synthesis of furonaphth[1,3]oxazine and furo[1,3]oxazinoquinoline derivatives as
      precursors for an o-quinonemethide structure and potential antitumor agents.
AB  - The synthesis of dihydro furonaphth[1,3]oxazine derivatives 3 was performed
      through a Mannich-type condensation between 2-cyano-5-hydroxy-3
      methylnaphtho[1,2]furan 2a, 1.5 eq of a primary amine and 3 eq of formaldehyde.
      Similarly, 2-cyano-5-hydroxy-3-methylfuro[2,3-f]quinoline 2b gave the dihydro
      furo[1,3]oxazino-quinoline compounds 4. Heating a mixture of the naphthofuran 2a,
      tert-butylamine and formaldehyde at toluene reflux led to the furonaphthoxazine
      3e, which decomposes to afford an o-quinonemethide intermediate 5. The latter was
      trapped with 1-morpholinopropene to give a dihydro furonaphthopyran derivative 6.
      All compounds 2, 3, 4 and 6 were assayed for in vitro cytotoxic activity toward L
      1210, MDA-MB 231 and PC tumor cells. Among them, furonaphth[1,3]oxazines 3b, 3c,
      and furo[1,3]oxazinoquinolines 4c, 4d showed significant activity against L 1210
      cells, while furoquinoline 2b was the most cytotoxic compound towards all three
      cell lines.

PMID- 8882459
TI  - Cyclic pentapeptide endothelin A receptor antagonists with attenuated in vivo
      clearance.
AB  - A series of analogues of BQ-123 (1), a potent cyclic pentapeptide endothelin A
      receptor antagonist, with amino acids linked to the side-chain of the Pro residue
      via an ester linkage was synthesized. All analogues synthesized exhibited potent
      endothelin A receptor binding affinity similar to that of 1. Of the synthesized
      analogues, the Lys, Arg and N alpha,N epsilon-dimethyllysine analogues, 9d-f,
      exhibited about a three-fold attenuation of in vivo clearance compared with 1. In
      rats, these analogues exhibited a 3-fold-higher plasma concentration and a longer
      retention time in plasma as compared with those of 1. The attenuated in vivo
      clearance was thought to be a consequence of decreased extraction of the
      compounds from the blood via the hepatic anion transport system, which
      efficiently extracts 1 from the blood.

PMID- 8882460
TI  - Cytotoxic cardenolides from woods of Euonymus alata.
AB  - Three cytotoxic cardenolides, acovenosigenin A 3-O-alpha-L-ramnopyranoside (1),
      euonymoside A (2) and euonymusoside A (3), were isolated from the woods of
      Euonymus alata (Celastraceae). The chemical structure of a new cardenolide,
      euonymusoside A (3) has been elucidated on the basis of extensive spectral
      analysis and enzymic hydrolysis to be acovenosigenin A (1 beta, 3 beta, 14 beta
      trihydroxy-5 beta-cardenolide) 3-O-beta-D-glucopyranosyl (1-->6)-beta-D
      glucopyranosyl(1-->4)-alpha-L-rhamnopyranoside. All three showed potent cytotoxic
      activity against some neoplastic cell lines.

PMID- 8882461
TI  - Inhibition mechanisms of staurosporine and H7 to cAMP-dependent protein kinase
      through docking study.
AB  - Inhibition mechanisms of staurosporine and H7 to cAMP-dependent protein kinase
      have been investigated through docking studies. For each molecule, the
      energetically most stable docking model was searched by using the
      conformationally flexible automatic docking program ADAM without any
      presumptions. The results explain well the observation that staurosporine does
      not bind to the enzyme competitively with H7, even though the two compounds
      competitively inhibit ATP binding.

PMID- 8882462
TI  - Ventricular arrhythmias in heart failure.
AB  - In the management of patients with chronic heart failure, our attention is
      shifting from just improving left ventricular function and abolishing ventricular
      arrhythmias to improving personal longevity. Importantly, sudden cardiac death is
      a pattern of death in as many as a half of patients with chronic heart failure.
      Arrhythmias are common in this disorder, but may possibly be a marker of diseased
      heart rather than a predictor of sudden cardiac death. The mechanisms and
      triggers of rapid ventricular tachycardia or fibrillation responsible for sudden
      cardiac death have not been well established. At present, it is important to be
      reminded that pharmacologic augmentation of cardiac contractility or suppression
      of asymptomatic ventricular arrhythmias is not an effective approach to
      preventing sudden cardiac death, but may even be deleterious. Three groups of
      drugs that have shown efficacy in preventing sudden cardiac death in patients
      with chronic heart failure are amiodarone, beta-blockers, and angiotensin
      converting enzyme (ACE) inhibitors. Although how these drugs improve prognosis of
      heart failure are not clear at present, myocardial protection by these agents
      appears to be most important.

PMID- 8882463
TI  - Training of a cardiologist in the United States.
AB  - Cardiology training in the United States has been evolving into well organized
      programs aiming at providing comprehensive education in all areas of cardiology-
      invasive, non-invasive, clinical, and research. Changes in the overall healthcare
      system are being reflected in more intensive training of fewer cardiologists who
      will function as consultants and directors of cardiology care. In this paper,
      trends in cardiology training programs in the United States, and in our own
      institution in particular, are described and discussed.

PMID- 8882464
TI  - Is nitric oxide really important for regulation of the cerebral circulation? Yes
      or no?
AB  - Since endothelium-dependent relaxation of cerebral vessels was first identified
      in 1980, the pivotal role of the endothelium has become evident not only in
      dilator responses but also in constrictor responses to various kinds of
      stimulation. Involvement of endothelium-derived relaxing factors (EDRFs) as well
      as endothelium-derived contracting factors (EDCFs) has been postulated in such
      vascular responses. In 1987, one of the EDRFs was determined to be nitric oxide
      (NO), a simple and very labile molecule, whereas endothelin composed of 21 amino
      acid residues was identified as one of the EDCFs in 1988. Since 1990, numerous
      studies which exclusively employed L-arginine analogues as specific NO synthase
      (NOS) inhibitors, have been undertaken to examine the role of NO in the
      regulation of the cerebral circulation. However, some conflicting data have
      emerged. The few points of consensus among the researchers may be summarized as
      follows: (1) NO, probably produced in the endothelium, plays an important role in
      the maintenance of the basal cerebral blood flow, (2) NO is not directly involved
      in hypoxic vasodilation, and (3) NO mediates a functional coupling of metabolism
      and cerebral blood flow in certain types of neural activation. Hypercapnic
      vasodilation and autoregulatory responses are still the main topics providing
      conflicting data with substantial areas of controversy. Besides ensuring
      appropriate experimental protocols, future studies require the precise monitoring
      of the degree and cellular specificity (endothelium, perivascular nerve fibers,
      neurons, etc.) of NOS inhibition in order to obtain concrete and reliable
      experimental data.

PMID- 8882465
TI  - Prenatal diagnosis of inherited skin diseases.
AB  - Significant advances in the prenatal diagnosis of hereditary skin disorders,
      including severe forms of epidermolysis bullosa (EB) and tyrosinase-negative
      oculocutaneous albinism (OCA1A), have been reviewed. Fetal skin biopsy during the
      second trimester of pregnancy has been utilized successfully for the prenatal
      diagnosis of EB and OCA1A. Recently, elucidation of the specific gene mutation in
      affected individuals allowed us to perform DNA-based prenatal diagnosis during
      the first trimester of pregnancy. Over the last 5 years, we have established
      several new strategies for prenatal diagnosis for EB and OCA1A at the Special
      Clinic for Inherited Skin Disorders at Keio University Hospital.

PMID- 8882466
TI  - Molecular basis of embryo implantation.
AB  - Implantation following placentation is a unique system for mammals to reproduce.
      The initial attachment of the embryo to the uterus occurs via the apical cell
      membranes of two epithelial cells, trophoblast of the blastocyst and surface
      epithelial cells of the endometrium. Analysis of the implantation at the
      molecular level has been a difficult problem in reproductive biology. Recently, a
      major break through was made in this area: A discovery of a novel cell adhesion
      molecule complex mediating the initial attachment of trophoblast to the
      endometrial epithelium. This review provides a brief overview of cell adhesion
      molecules involved in implantation and introduces identification and
      characterization of trophinin and tastin.

PMID- 8882467
TI  - Hemolytic uremic syndrome following hemorrhagic colitis caused by verotoxin
      producing Escherichia coli O157:H7: early signs of hemolytic uremic syndrome.
AB  - Ten cases of hemolytic uremic syndrome (HUS) following hemorrhagic colitis caused
      by verotoxin T2-producing Escherichia coli O157:H7 (VTEC) occurred in a
      Kindergarten. Slight changes in results of peripheral blood and blood chemistry
      studies an average of 4 days after onset suggested HUS, and within the following
      12 hours platelet counts and levels of haptoglobin and lactic dehydrogenase
      decreased. Treatment was mainly directed toward the management of renal failure
      and included supportive therapy and anticoagulant and antiplatelet treatment.
      Although neurological complications occurred in some cases, all patients
      eventually recovered completely.

PMID- 8882468
TI  - Enhancing effect of the liver extract and flavin adenin dinucleotide mixture on
      anti-viral efficacy of interferon in patients with chronic hepatitis C.
AB  - A combined preparation of liver extract and flavin adenin dinucleotide (FAD)
      (Adelavin) has been widely used in patients with chronic liver diseases in Japan.
      One milliliter of this agent contains 15 microliters of phenol-soluble phase of
      liver nucleic acid fraction and 10 mg of FAD. To examine the advantages of using
      this preparation in the elimination of hepatitis C virus (HCV) from patients with
      chronic hepatitis (CH)-C receiving interferon (IFN), 2 ml of this preparation was
      intravenously (n = 9) or intramuscularly (n = 8) administered daily for 5 days
      before 6 million units of IFN-alpha was intramuscularly injected once. Before and
      48 hours after the injection of IFN, serum ALT, 2'5'-oligoadenylate synthetase
      (2'5-AS) activity, and HCV RNA levels were measured. The daily administration of
      this preparation alone for 5 days did not significantly change serum ALT, 2'5-AS
      activities, and HCV RNA levels. The 2'5-AS activities were significantly
      increased by IFN after the intravenous injection of this preparation (p < 0.01),
      while an injection of IFN alone of this dose did not change its activities (n =
      10). HCV RNA levels were significantly decreased by IFN only after the
      administration of the preparation (intramuscular, p < 0.01; intravenous, p <
      0.01). The effect of intravenous injection of this preparation was also elicited
      in patients with HCV genotype II and with HCV more than 10(5) copies/ml. These
      results suggest that this preparation may enhance the 2'5-AS production by IFN as
      a result of the increase in mitochondrial adenosin triphosphate production and
      may be a potent agent to enhance the anti-viral efficacy of IFN in patients with
      CH-C.

PMID- 8882469
TI  - Adjuvant cyclophosphamide, methotrexate and 5-fluorouracil versus
      cyclophosphamide plus futraful for premenopausal patients with stage I-II and one
      to three-node-positive breast cancer: results of a prospective randomized study.
AB  - A prospective randomized study was conducted to compare the adjuvant efficacy of
      12 cycles of low-dose CMF (cyclophosphamide: CPA, methotrexate; MTX, 5
      fluorouracil; 5-FU) with that of orally administered CPA plus FT (futraful) in
      premenopausal patients with stage I-II and one- to three-node-positive breast
      cancer. The 12-cycle CMF group (91 patients) received, 100 mg CPA orally on days
      1 to 14 plus 20 mg MTX and 500 mg 5-FU intravenously (iv) on days 1 and 8 of each
      cycle. The CPA plus FT group (85 patients) received 100 mg CPA and 600 mg FT
      orally each day for one year. The background characteristics of the two groups
      were comparable. At 5 and 10 years, there were non-significant trends towards
      better disease-free and overall survival rates in the CMF group. Both treatments
      were well tolerated, but more patients in the CPA plus FT group refused to
      continue chemotherapy because of continuous gastrointestinal disturbances. No
      clear benefit of adding low-dose MTX to CPA and fluoropyrimidines was observed in
      this subgroup of Japanese patients. Further studies will be required to clarify
      the superiority of conventional-dose of CMF treatment to orally administered CPA
      plust FT treatment.

PMID- 8882470
TI  - Modulation of elastin expression and cell proliferation in vascular smooth muscle
      cells in vitro.
AB  - Elastin expression in cultured vascular smooth muscle cell (VSMC) was found to be
      enhanced by potent inhibitors of VSMC proliferation including minoxidil, heparin
      and retinoic acid. By contrast, elastin expression was declined by potent
      stimulators of VSMC proliferation like epidermal growth factor, high K+,
      angiotension II and phorbol ester. To elucidate the relationship between elastin
      expression and cell proliferation, the elastin expression in the different cell
      growth states brought by cell-synchronizing culture or suspension culture, a
      culture system independent of potent modulators of VSMC proliferation. Elastin
      was found to be expressed maximally at G0 and minimally at G2/M phases,
      suggesting that cell growth state regulates elastin expression in VSMC culture.
      Synthetic elastin peptide VPGVG or its polymeric form (VPGVG)n enhanced VSMC
      proliferation, which resulted in the reduction of elastin expression. The results
      suggests that elastin fragment regulates VSMC proliferation. These correlation
      between elastin expression and cell growth state may play an essential role in
      elastin metabolism under the normal and diseased conditions.

PMID- 8882471
TI  - Helicobacter pylori infection and serum pepsinogen I concentration in peptic
      ulcer patients: effect of bacterial eradication.
AB  - OBJECTIVES: In order to test the hypothesis that H. pylori infections in the
      gastric antrum increase pepsinogen I release, fasting serum pepsinogen I
      concentrations were compared in peptic ulcer patients with and without H. pylori
      infection. A randomized prospective study was performed to determine whether the
      increased serum pepsinogen I concentrations associated with H. pylori infection
      respond to treatment that eradicates H. pylori. METHODS: Fasting serum pepsinogen
      I concentrations were measured by RIA in 736 patients with endoscopically and
      histologically confirmed benign peptic ulcer with and without H. pylori
      infection. Out of 511 patients with H. pylori infection, 110 patients (group 1)
      were randomly selected and were treated with metronidazole and tripotassium
      dicitrato bismuthate combined with ranitidine and antacid, and 97 patients (group
      2) were treated only with ranitidine and antacid. The third group, 54 patients
      free of H. pylori infection, was designed to evaluate the influence of H2
      receptor antagonist and antacid on the change of pepsinogen I. Fasting pepsinogen
      I concentration and H. pylori status were compared before and after the
      treatment. RESULTS: Patients infected by H. pylori (gastric ulcer 208, duodenal
      ulcer 303; total 511) had significantly higher fasting serum pepsinogen I
      concentrations than H. pylori negative patients (gastric ulcer 110, duodenal
      ulcer 115; total 225). Mean pepsinogen I level of the former was 124.3 +/- 46.9
      and that of the latter was 77.9 +/- 25.8 ng/ml. (p < 0.0001). The difference in
      serum pepsinogen I concentrations according to the location of ulcer crater was
      significant only in non-infected subjects e.g., mean pepsinogen I level H. pylori
      negative gastric ulcer was significantly lower than that of H. pylori-negative
      duodenal ulcer patients. H. pylori was eradicated in all the patients who had
      received antibacterial therapy for 4 weeks and serum pepsinogen I concentrations
      were significantly decreased from 129.8 +/- 43.0 to 82.4 +/- 24.0 ng/ml after
      eradication of the organism. (p < 0.0001) In contrast, H. pylori-positive
      patients who had not received antibacterial therapy were still infected at the
      completion of the study and there was no significant change in the serum
      pepsinogen I concentrations after the treatment (120.8 +/- 40.9 vs 126.3 +/- 40.4
      ng/ml). (p > 0.57) None of the patients who were initially H. pylori-negative has
      been reinfected during the period of the study and their serum pepsinogen I
      concentrations were not changed. (pre-treatment value 75.1 +/- 8.0; post
      treatment value 77.3 +/- 24.5 mg/ml) (p < 0.75) Four-to six-week therapy of H2
      receptor antagonist and antacid did not exert any influence on serum pepsinogen I
      concentrations. CONCLUSIONS: On the basis of our results, we have confirmed that
      the chronic infection of H. pylori of gastric antrum in peptic ulcer patients
      causes increased pepsinogen I release into the circulation, and eradication of
      the organism results in significant fall in serum pepsinogen I concentrations.

PMID- 8882472
TI  - Clinical features of ulcerative colitis in Korea.
AB  - OBJECTIVES: This study was conducted to investigate the clinical features of
      ulcerative colitis in Korea and to evaluate the clinical course after medical
      therapy. METHODS: Symptoms, signs and results of the treatment were
      retrospectively analyzed in 66 patients (male 32, female 34) diagnosed to have
      ulcerative colitis at the Asan Medical Center. RESULTS: The median age of the
      beginning of symptoms was 36 years (range, 14-72). Diarrhea and rectal bleeding
      were observed in 95.1 and 91.4%, respectively, at the time of diagnosis, while
      extra-colonic manifestations were observed in 24.1%. In 41 patients (62.1%),
      colitis developed in the rectum and sigmoid colon, while left colitis and
      extensive colitis developed in 11 (16.7%) and 14 patients (21.2%), respectively.
      The severity of disease was determined according to the clinical criteria,
      resulting in 22 (33.3%) mild, 21 (31.8%) moderate and 23 (34.8%) severe diseases.
      The seventy was also classified as 1, 2 and 3 by sigmoidocolonoscopic findings:
      1;17 patients(25.8%), 2;27(40.9%) and 22(33.3%). Among 23 patients with severe
      disease, 5 patients (7.6%) received total colectomy due to toxic megacolon,
      intractability to medical therapy, ileocolic fistula and intestinal stenosis. The
      severity determined by colonoscopic findings was well correlated with that
      determined clinically and was closely related to the severity of symptoms, levels
      of albumin, hemoglobin and the count of leukocyte. The median duration of
      symptoms before treatment was 4 weeks (range, 11-300). All patients were treated
      with sulfasalazine and prednisolone. All patients with medical therapy, except 2
      patients (96.7%), obtained clinical remission. The median days required for
      remission was 14 (range, 3-70). Relapse rates at 6 months, 1 year and 2 years
      after the initiation of treatment were 19.7, 34.1 and 49.3%, respectively. The
      median disease-free interval from the time of remission was 10 months (range, 2
      60). After remission, the subsequent relapse rate increased in severe disease,
      while no difference was observed between the disease extents. CONCLUSIONS: The
      general characteristics of clinical manifestations and clinical course, after the
      medical treatment of ulcerative colitis in Korean patients, are not considerably
      different from those in Western countries.

PMID- 8882473
TI  - Changes of atrial natriuretic peptide level in patients with nephrotic syndrome
      after supine bicycle exercise.
AB  - OBJECTIVES: The exact role of atrial natriutetic peptide (ANP) in the
      pathogenesis of edema in nephrotic syndrome (NS) has not been fully elucidated.
      We aimed to investigate the possible contribution of ANP to edema formation in
      NS. METHODS: We subjected 18 nephrotic subjects and 20 healthy volunteers to
      supine bicycle exercise (SBE), a maneuver that seemed to increase venous return
      and to enhance the release of ANP. Plasma concentrations of immunoreactive-ANP
      were measured before and after SBE by radioimmunoassay. RESULTS: There was a
      significant rise in the plasma concentration of ANP in the controls after SBE
      (from 31.1 +/- 6.16 to 42.0 +/- 6.01 pg/ml: p < 0.05). Meanwhile, there was no
      change in plasma concentration of ANP in the patients with NS (from 35.4 +/- 6.04
      to 35.1 +/- 5.31 pg/ml). The change in plasma concentration of ANP in controls
      was significantly different from that in those with NS (p < 0.05). The mean
      baseline value of ANP in controls was the same as in NS. CONCLUSIONS: These
      results show that SBE was a simple maneuver to stimulate the release of ANP in
      healthy controls. In contrast, it failed to stimulate the release of ANP in
      subjects with NS.

PMID- 8882474
TI  - Influence of 17- alpha-estradiol on catecholamine secretion from the perfused rat
      adrenal gland.
AB  - OBJECTIVES: It has been known that adrenal corticosteroids influence the
      expression of adrenomedullary catecholamine-synthetizing enzymes and also
      suppress the emission of axonal-like processes in cultured chromaffin cells. In
      the present study, it was attempted to investigate the effect of 17-alpha
      estradiol on catecholamine (CA) secretion evoked by acetylcholine (ACh). DMPP.
      McN-A-343, excess K+ and Bay-K-8644 from the isolated perfused rat adrenal gland.
      METHODS: Mature male Sprague-Dawley rats were anesthetized with ether. The
      adrenal gland was isolated by the method of WaKade. A cannula used for perfusion
      of the adrenal gland was inserted into the distal end of the renal vein. The
      adrenal gland, along with ligated blood vessels and the cannula, was carefully
      removed from the animal and placed on a platform of a leucite chamber. RESULTS:
      The perfusion of 17-alpha-estradiol (1-100 uM) into an adrenal vein for 20 min
      produced relatively dose-dependent inhibition in CA secretion evoked by ACh (5.32
      mM). DMPP (100 uM for 2 min). McN-A-343 (100 uM for 2 min) and Bay-K-8644 (10 uM
      for 4 min), while it did not affect the CA secretory effect of high K+ (56 mM).
      Also, in the presence of 17-beta-estradiol. CA secretion of ACh. DMPP and McN-A
      343, without any effect on excess K(+)-evoked CA sectretion was depressed.
      However, in adrenal glands pre-loaded with 17-alpha-estradiol (10 uM) plus
      tamoxifen (2 uM), which is known to be a selective antagonist of estrogen
      receptors (for 20 min). CA secretory responses evoked by ACh. DMPP and McN-A-343
      were condiderably recovered as compared to that of 17-alpha-estradiol only, but
      excess K(+)-induced CA secretion was not affected. However, pre-treatment with 17
      alpha-estradiol in the presence of meclopramide (dopaminergic antagonist) did not
      affect the secretory effect of CA evoked by ACh. DMPP, McN-A-343 and high
      potassium. CONCLUSIONS: These results suggest that 17-alpha-estradiol causes the
      marked inhibition of CA secretion evoked by cholinergic receptor stimulation, but
      not that by excess K+, indicating strongly that this effect may be mediated by
      inhibiting the influx of extracellular calcium into the rat adrenomedullary
      chromaffin cells through the activation of inhibitory estrogen receptors, and it
      also plays a modulatory role in regulating CA secretion.

PMID- 8882475
TI  - Prognostic factors of patients with thymoma.
AB  - OBJECTIVES: To analyze the prognostic factors influencing the survival of
      patients with thymoma, clinical characteristics, treatment modalities and
      survival of patients were evaluated. The efficacy of chemotherapy was also
      determined. METHODS: Retrospective study was done on one hundred patients whose
      diagnosis was confirmed pathologically at Seoul National University Hospital from
      1981 to 1994. The staging was carried out according to the Masaoka system.
      Survival rate was calculated by the Kaplan-Meier method and prognostic factors
      were analyzed by a multivariate analysis (Weibull model). RESULTS: The stage of
      100 patients was as follows: Stage I-50, II-6, III-27, IV A-10, IV B-7. The
      overall survival rates at 5 and 10 years after diagnosis were 73.1% and 58.7%,
      respectively. The 5-year survival differences, according to various prognostic
      factors, were as follows: 1) Stage: I-92.8%, II-100%, III-71.6%, IVA-25.9% and
      IVB-32.9% (p = 0.0029). 2) Age: < 60 years-79.5% and > or = 60 years-41.5% (p =
      0.0489). 3) Extent of resection: Total patients: complete resection-87.6% and
      incomplete resection-50.5% (p > 0.05) Stage III: complete resection-66.7% and
      incomplete resection-75.5% (p > 0.05) 4) Myasthenia gravis: present-71.6% and
      absent-74.9% (p > 0.05) Seventeen patients were treated with a combination
      chemotherapy of Cyclophosphamide, Adriamycin and cisplatin(CAP). Two complete
      responses and seven partial responses (overall response rate of 53%) were
      observed with a median response duration of fourteen months. Combination
      chemotherapy with CAP was effective. CONCLUSIONS: Stage and age were the
      independent prognostic factors in patients with thymoma. However, the presence of
      myasthenia gravis or the extent of resection in stage III patients was not
      associated with the survival time.

PMID- 8882476
TI  - A comparison of serum CYFRA 21-1 and SCC Ag in the diagnosis of squamous cell
      lung carcinoma.
AB  - To evaluate the usefulness of CYFRA 21-1 and SCC Ag in the diagnosis of squamous
      cell carcinoma (SQC) of the lung, we tested sera from 124 patients with lung
      cancers (squamous cell ca 72, adenoca 22, large cell ca 4, small cell ca 18 and
      undetermined 8) and 78 patients with inflammatory lung diseases (bronchitis 24,
      bronchiectasis 29, tuberculosis 19 and others 6) using immunoradiometric assay
      kit for cytokeratin fragment 19 (CYFRA 21-1) and radioimmunoassay kit for SCC Ag.
      The serum CYFRA 21-1 and SCC Ag were significantly higher in lung cancer patients
      compared with control subjects. However, the significant difference was
      restricted only to SQC. In patients with SQC, CYFRA 21-1 and SCC Ag showed
      significantly higher levels according to the advanced anatomic stages (stage I
      IIIa vs. stage IIIb, IV, p < 0.05). There was a good correlation between CYFRA 21
      1 and SCC Ag (r = 0.41, p < 0.001). Receiver operating characteristic (ROC)
      curves were generated from results of both tumor markers and areas under the
      curves (AUC) were calculated. AUC of CYFRA 21-1 (0.93) were significantly larger
      than that of SCC Ag (0.77) for the diagnosis of SQC (p < 0.05). Therefore, we
      conclude that CYFRA 21-1 is superior to SCC Ag in the diagnosis of squamous cell
      carcinoma of the lung.

PMID- 8882477
TI  - Combined cis-platinum and alpha interferon therapy of advanced hepatocellular
      carcinoma.
AB  - To evaluate the clinical efficacy of alpha-interferon(IFN-alpha) plus cis
      platinum in hepatocellular carcinoma(HCC). 56 inoperable patients with HCC were
      divided into IFN-alpha plus cis-platinum treated group (n = 30) and no antitumor
      therapy group (n = 26). The survival of IFN-alpha plus cis-platinum treated
      patients was significantly better than that of patients who received no antitumor
      therapy (p = 0.001). Median survival time was 33 weeks and 14.0 weeks,
      respectively. The cumulative estimated survival rates of our IFN-alpha plus cis
      platinum treated group (93.5% at 3mo, 75.0% at 6mo) were for longer than that of
      the no antitumor therapy group (84.6% at 3mo, 57.7% at 6mo). Objective tumor
      regression, greater than 50% was observed in 13.3% (4 of 30) of patients
      receiving IFN-alpha plus cis-platinum. By the univariate analysis, the absence of
      portal vein thrombus (p < 0.05), alkaline phosphatase lesser than 280 U/L (p =
      0.001), total bilirubin less than 2.0 mg% (p < 0.05), serum triglyceride less
      than 155 mg/dl (p < 0.05) were shown to be the factors most significantly
      favoring a better survival. By the multivariate analysis, using Cox proportional
      hazards model, IFN-alpha plus cis-platinum treated group (p = 0.0001), alkaline
      phosphatase less than 280 mg/dl (p = 0.005), the absence of portal vein thrombus
      (p = 0.020) were independent favorable prognostic factors. We conclude that IFN
      alpha plus cis-platinum is useful in patients with inoperable HCC and the above
      favorable prognostic factors may also be useful in the design and analysis of
      future clinical trials of systemic chemotherapy for HCC.

PMID- 8882478
TI  - Increased neutrophil chemotactic activity is noted in alminum-induced
      occupational asthma.
AB  - A worker with occupational exposure to aluminum powder developed asthmatic
      symptoms three years and six months after starting work. Skin tests (prick and
      intradermal) to aluminum chloride (AlCl3) were negative. Inhalation challenge
      test with 10 mg of aluminum powder and 10 mg/ml of AlCl3 solution induced an
      early asthmatic response. Sodium cromoglycate pre-treatment reduced AlCl3-induced
      bronchoconstriction. Neutrophil chemotactic activity was markedly increased one
      and seven hours after the challenge procedure, which was lessened with sodium
      cromoglycate pre-treatment. Aluminum can induce occupational asthma in exposed
      worker, which may be mediated by a non-immunologic mechanism and the possible
      role of neutrophils was suggested.

PMID- 8882479
TI  - PGF2 alpha causes bronchoconstriction and pulmonary vasoconstriction via
      thromboxane receptors in rat lung.
AB  - We determined the vascular and airway effects of PGF2 alpha and its mechanism of
      action on isolated-perfused lungs of rats were isolated and perfused at 50
      ml/kg/min with Krebs-Henseleit bicarbonate buffer solution containing 3% bovine
      serum albumin. The lungs were ventilated with 21% O2 and 5% CO2 at a tidal volume
      of 2 ml. frequency of 60 per minute and positive end expiratory pressure of 3
      cmH2O. Following injection of 50 micrograms PGF2 alpha into the afferent
      pulmonary catheter, there was a marked rise in pulmonary arterial pressure (Ppa)
      and in resistance to airflow across the lung (RL) and a fall in dynamic lung
      compliance (Cdyn). Double vascular occlusion technique revealed that 29% of the
      rise in Ppa was due to an increase in upstream and 71% to downstream resistance.
      N omega-nitro-L-arginine, 100 microns, a NO synthase inhibitor potentiated the
      Ppa response two-fold with significant change in airway mechanics. Rat atrial
      natriuretic factor (r-ANF), 40 micrograms quickly reversed the changes in Ppa, RL
      and Cdyn. Infusion of r-ANF prior to PGF2 alpha attenuated the Ppa response by
      38%, RL by 44% and Cdyn by 12%. SQ 29548, a thromboxane receptor blocker and Cl,
      a protein kinase C (PKC) inhibitor, fully blocked both the vascular and airway
      responses to PGF2 alpha. PGF2 alpha is a constrictor of pulmonary vessels and
      airways in rat lungs via thromboxane SQ 29548 receptors, thansduced by
      intracellular PKC.

PMID- 8882480
TI  - A case of Budd-Chiari syndrome with high antiphospholipid antibody in a patient
      with systemic lupus erythematosus.
AB  - Antiphospholipid syndrome is characterized by recurrent episodes of arterial and
      venous thrombosis, spontaneous fetal losses, thrombocytopenia and persistently
      elevated levels of antiphospholipid antibodies. We experienced a case of Budd
      Chiari syndrome in a 32-year old female lupus patient who was presented with left
      leg edema, ascites and esophageal varix. The clinical and laboratory findings
      were compatible with the cirteria for systemic lupus erythematosus (SLE) and she
      was found to have anticardiolipin antibody, thrombocytopenia and prolonged
      partial thromboplastin time. Initially, she was treated with intravenous heparin
      and uroki nase and she was followed up with warfarin, baby aspirin and steroids.

PMID- 8882481
TI  - Acute lung injury after phosgene inhalation.
AB  - Phosgene (COCl2) is a colorless oxidant gas which is heavier than air and the
      lethal exposure dose (LC50) in humans is 500 ppm/min. This gas was originally
      manufactured as an agent for chemical warfare during World War I and there had
      been a great deal of studies on phosgene poisoning during the early years of
      industrial use. It is still widely used in the synthesis of chemicals and
      plastics. In the modern era, however, phosgene poisoning is relatively uncommon
      except in accidental exposures. In Korea, there has been no report about lung
      injury from phosgene inhalation. We present a clinical experience with six
      patients accidentally exposed to phosgene.

PMID- 8882482
TI  - [Regional aging in Germany].
AB  - Elderly people in Germany have a specific regional distribution. Recent regional
      population projections show that these patterns will change. The most dynamic
      process of aging will take place in the suburban parts of the large western
      Germany agglomerations, whereas in eastern Germany aging concentrates in regions
      with a lower density. There will be a regional deconcentration of elderly people
      with consequences for the planning of infrastructure.

PMID- 8882483
TI  - [Development of disability in the elderly].
AB  - In two representative infratest-surveys, needs for care were systematically
      assessed regarding 24 basic activities of daily living (hygiene, mobility,
      communication, etc.). About 1.2 million persons in private homes and .5 million
      in homes for the elderly or handicaped were found to need care at least once a
      day. Impaired mobility was a persisting characteristic, partly due to physical
      disability, partly due to cognitive deficits. Being unable to phone or to
      orientate oneself outside the home, for instance, points to dementia. For the
      future, an increase in the number of persons who are dependent on care to 1.32
      million in private homes and 900,000 who probably will live in homes for elderly,
      can be calculated for the year 2040 as a consequence of the demographic impact.
      Nevertheless, also in the future nearly one out of two elderly will be able to
      live independently without any need of care or help. Self-maintenance can be
      identified as the essential problem, because people with need of care will
      increasingly live alone without any relatives.

PMID- 8882484
TI  - [Unequal conditions for longevity--determinants of mortality from the
      longitudinal perspective].
AB  - Longitudinal data of the German Socioeconomic Panel (GSOEP) offer new
      possibilities to identify the determinants for longevity respective the mortality
      risk. A panel probit model shows that beyond the cohort effects a low income
      position and a low educational level are determinants which increase the
      mortality risk dramatically. Widowhood and small family size also have increasing
      effect on mortality for men while marital status of single (unmarried, separated,
      divorced) has shortening effect on a woman's life expectancy. Reduced societal
      participation creates conditions which increase the mortality risk.

PMID- 8882485
TI  - [Demographic change, job market development and employment perspectives of
      elderly workers].
AB  - Demographic change will also have a strong influence on the labor market. The
      rate of younger employees is decreasing and the average age of the workforce is
      increasing. This does not imply, however, that the chances for older employees in
      the labor market will improve or that their working-life will be prolonged. As
      long as the labor market situation is difficult, the trend towards early
      retirement cannot be reversed. An increase in unemployment figures would be the
      consequence. But since employers will have to rely on the productivity of older
      employees after the turn of the millenium, action has to be undertaken now to
      promote the employment-related opportunities of older persons. Flexible working
      time arrangements and part-time work for older employees in particular could be
      good measures to increase the retirement age and to reduce working time in total.

PMID- 8882486
TI  - [Family relations and informal social networks in the social structure and
      demographic change].
AB  - Demographic changes and social structural transformations lead to changes in
      family size, the family cycle and in intergenerational relationships. Contrary to
      an abridged and overgeneralized public, political and scientific discussion, one
      can, by no means, assume a decrease in family functions concerning the aged. It
      seems that in some areas emotional and instrumental functions of the family
      increase. In other areas functions are transferred and generally there is a whole
      new division of labor between family and other informal networks. These informal
      networks are obviously becoming increasingly meaningful in the sense of a family
      "freely chosen". Because of considerable variability in social structure
      generalizations in this area cannot be made. On the whole, one can expect a
      continuing expansion and differentiation in the range and type of support offered
      the elderly by the family and other networks.

PMID- 8882487
TI  - [Social networks of elderly migrants: on the relevance of familial and intra
      ethnic support].
AB  - In a research project elderly migrants were interviewed about the size and
      composition of their social networks. First, the results indicate variations of
      network size by age, family status and gender: older, single and female
      participants have smaller networks than younger, married and male participants.
      Second, elderly migrants often have large sociability networks, but with regard
      to instrumental and emotional support the interviewed elderly migrants only can
      dispose of a few, mainly close family network members. Finally, a strong
      orientation of the elderly migrants to persons of their own ethnic group could be
      observed: with regard to all types of social support a distinct superiority of
      intraethnic relationships was found. Considering the predicted overburdening and
      reduction of the ethnic family-oriented support networks of the elderly migrants,
      the socio-political system must provide appropriate measures.

PMID- 8882488
TI  - [Demands on the legal pension security system based on the demographic change].
AB  - This paper deals with the German public pension system which is affected by
      changing demographics. It examines whether the problems can be solved more
      efficiently by either a fundamental change towards a tax-financed basic allowance
      augmented by a private capital accumulation sheme, or by adjustments within the
      present system of wage-determined contributions. The analysis shows that basic
      allowance and capital accumulation systems are inadequate, essentially for
      macroeconomic reasons and adverse effects on redistribution, to the
      demographically induced problems of the public pension system.

PMID- 8882489
TI  - [Social services and the pressure to modernize: new needs and developmental
      trends in care of the elderly].
AB  - Demographic and sociostructural changes put pressure on care services for the
      elderly within the German welfare system: There is a need for facilities and new
      concepts. This also requires more and flexible domestic services, which are
      poorly developed in the German social system. Because the German range of care
      provider types is easy to navigate, there is increased demand for consumer
      information and recommendations. Considering the domains of care services, which
      have been widely distributed to the powerful non-profit welfare organizations,
      the status quo vs. new flexible service will challenge consumers confidence and
      choice, especially since todays elderly are more active and have more expendable
      income. The recently instituted "long-term care insurance" encourages, for the
      first time, competition between nonprofit organizations and commercial providers.
      Nevertheless, a clearly perceptible "polarization of age" draws attention to
      persisting challenges to social policy. Therefore, the increasing competition
      among types of care providers urges for a truly independent quality control, as
      well as an effective "welfare mix".

PMID- 8882490
TI  - [Recent problems of advanced age in humans. I. General problems].
AB  - The obvious increase of human age even up to above one hundred years in nearly
      all civilised countries leeds the autor to discuss the following actual
      gerontologic problems: the needs for further splitting of categories of high age,
      the reasons for the rapid increase of the oldest-old group and the predicted
      "mushroom"-shaped age-pyramid in Germany. Further subjects are the liability of
      age-declaration in the highest age group according to the strict directions by
      Kannisto, the total account of men and women above one hundred years of age in
      different countries and in Germany since 1963, the difference between relative
      and absolute longevity and new molecular-biologic and genetic studies on extreme
      age.

PMID- 8882491
TI  - [Regional disparities in accessibility of inpatient treatment for elderly
      patients].
AB  - This article analyzes the supply of residential care facilities for old people in
      Germany with the aim to discover regional disparities. The analysis is based on
      the directory of residential institutions for old people (Altenheimadressbuch).
      On a national level the supply of residential care facilities in this data base
      is comparable with the results of the national statistic (Heimplatzstatistik).
      The results show considerable disparities that only to a minor extent coincide
      with the regional distribution of older people. Although there is no definite
      coherence between the supply of residential care facilities and the family care
      potential, there is a significant negative correlation between both.

PMID- 8882492
TI  - Target gene identification: target specific transcriptional activation by three
      murine homeodomain/VP16 hybrid proteins in Saccharomyces cerevisiae.
AB  - The mammalian homeodomain proteins encoded by Hox genes play an important role in
      embryonic development by providing positional queues which define developmental
      identities along the anteroposterior axis of developing organisms. These proteins
      bind DNA specifically through their homeodomain to sequences containing ATTA
      cores, and thereby are thought to exert their effect regulating downstream genes.
      Little is known about the specificity of binding of homeodomain proteins to their
      sequences and the identity of their target genes. We have developed a
      transcriptional activation assay in yeast which employs a homeobox/VP16 fusion
      gene as a transcriptional activator and a target construct in which test
      fragments of DNA are inserted upstream to a reporter gene. Using this assay, we
      compared transcriptional activation by three chimeric proteins containing the
      homeodomains of the mouse homeobox genes, Hoxa-5, Hoxb-6, and Hoxc-8. When tested
      on previously defined target sequences, strong differential specificities of
      activation were observed. In an effort to identify enhancers that normally
      respond to homeodomain transcriptional activators, random fragments of mouse
      genomic DNA were cloned upstream of the reporter gene. Genomic DNA fragments with
      distinct activation profiles were obtained and were found to share matches beyond
      the ATTA core with previously described enhancers. These results demonstrate that
      the transcriptional activation system in yeast can be used as a convenient system
      to detect DNA motifs which bind homeodomain proteins, and subsequently, to
      identify authentic target genes responsive to Hox gene proteins.

PMID- 8882493
TI  - Short-term effects of 3,5,3'-triiodothyronine on the intermediary metabolism of
      the dogfish shark Squalus acanthias: evidence from enzyme activities.
AB  - Plasma 3,5,3'-triiodothyronine (T3) concentration decreased significantly (P <
      0.05), during 1-5 days of captivity, from levels in the freshly caught dogfish
      shark Squalus acanthias. The short-term effects of T3 treatment on the
      intermediary metabolism of S. acanthias were measured in the gill, kidney, liver,
      and white muscle. Animals were kept for 1-5 days before experimentation. Three
      hours after an intraperitoneal injection with either a low T3 dose (8.3 pmol
      T3/kg fish) or a high T3 dose (830 pmol T3/kg fish), selected enzymes of amino
      acid metabolism, lipid catabolism, ketone body metabolism, glycolysis, and
      oxidative metabolism were measured. Activity of enzymes of amino acid metabolism
      and lipid catabolism increased significantly (P < 0.05) in the liver of fish
      treated with a low T3 dose. The low dose of T3 apparently influences glycolysis
      as pyruvate kinase activity significantly increase (P < 0.05) in the kidney and
      white muscle.

PMID- 8882494
TI  - Vitellogenin receptors during vitellogenesis in the rainbow trout Oncorhynchus
      mykiss.
AB  - Rainbow trout vitellogenin receptors have been characterized by ligand blotting
      and Scatchard analysis. Their evolution has been studied over a reproductive
      cycle in a broodstock of 2-year-old females. The receptors were prepared from
      ovarian membrane homogenates and were solubilized using n-octyl-beta-D
      glucopyranoside. The visualization of the receptor by ligand blotting using
      125iodine-vitellogenin after sodium dodecyl sulfate electrophoresis revealed the
      existence of one major binding component corresponding to a protein of 113 kDa.
      The Scatchard transformation of the binding data revealed a single class of
      binding sites with an apparent Kd of 1.8 x 10(-8) M/L. The variations of the
      binding characteristics (Kd and maximum binding) were investigated during
      vitellogenesis. This study revealed that the Kd was not affected by oocyte growth
      during vitellogenesis, but was highly decreased in ovulated eggs. The receptor
      number increased during the same period from 35 to 860 fM per oocyte, while the
      receptor number per mm2 of oocyte membrane surface was doubled during the same
      period.

PMID- 8882495
TI  - Characterization of growth hormone nycthemeral plasma profiles in catheterized
      rainbow trout (Oncorhynchus mykiss).
AB  - This study was conducted in order to characterize the nycthemeral plasma profiles
      of growth hormone (GH) in 41 prepubertal (2+) rainbow trout (Oncorhynchus
      mykiss). The possible influences of day-night alternation and of the food factor
      (quantity ingested, timing of the feed) on these plasma profiles were also
      analysed. Blood samples were taken every hour during a 24-hour period through a
      catheter inserted in the dorsal aorta. An assay of cortisol levels showed that
      the fish were in satisfactory physiological condition. The plasma concentrations
      of GH fluctuated significantly during the course of a nycthemere. The basal level
      was very low (0.32 +/- 0.01 ng/ml), and was interrupted by peaks that occurred at
      a rate of 2.1 +/- 0.1 peaks/24 hr, an amplitude of 2.0 +/- 0.3 ng/ml, and a
      duration of 3.5 +/- 0.2 hr. As a result, mean GH levels over a 24-hr period were
      low (0.7 +/- 0.1 ng/ml). Peaks occurred irregularly and asynchronously in
      individual fish and displayed no rhythmicity. Our study shows that there is a
      sexual difference in GH profiles in rainbow trout. No significant difference was
      observed between daily and nightly levels of GH (0.6 +/- 0.07 vs. 0.8 +/- 0.1
      ng/ml). No influence of the diet on the plasma profiles of GH was observed.
      Average levels of GH over a 24 hr period are not significantly correlated with
      the growth rate of the fish. This study shows that circulating levels of GH in
      rainbow trout are markedly lower than in other vertebrates.

PMID- 8882496
TI  - Regionally regulated conversion of protein expression in the skin during anuran
      metamorphosis.
AB  - The back skin of anuran larvae undergoes drastic metamorphic changes which are
      quite different from the tail skin. To have an insight into the mechanism of the
      region-dependent changes, we made a thorough survey of metamorphic alterations in
      protein expression in both the body and tail skin of Xenopus laevis tadpoles
      utilizing high-resolution two-dimensional electrophoresis. Approximately 400
      proteins were detected, 9 of which were identified as known proteins and were
      used as index proteins to standardize the readout of distribution of protein
      spots on gels. The overall pattern of polypeptide distribution (map) was
      classified into "larval type" and "adult type." The maps showed stage-specific
      changes. Up to stage 58 the back skin map remained the larval type, showed
      remarkable changes for the first time at stage 60 (whose pattern was a
      combination of both larval and adult types), and became the adult type at stage
      62. The basic feature of the tail skin map remained the larval type through the
      climax stage of metamorphosis. Experiments using tadpoles treated with an
      antithyroid drug showed that most of back skin proteins detected on the map are
      thyroid hormone responsive in their expression. Expression of keratin II (adult
      type keratin) was found to be uniquely regulated. As expected, silver staining
      detected it in the back but not in the tail. However, the protein-labeling
      experiment with [35S]methionine showed that the tail skin is actively
      synthesizing the adult keratin, suggesting that tail cells have a specific
      elimination mechanism of the protein.

PMID- 8882497
TI  - PCR-survey of Hox-genes of the zebrafish: new sequence information and
      evolutionary implications.
AB  - We analyzed the Hox gene complement of the zebrafish Danio rerio using a PCR
      survey. We found 18 new zebrafish HOM/Hox type sequences and one sequence of the
      msh group. For groups 1-3 and 8-10 we could unambiguously assign the zebrafish
      fragments to cognate groups. The assignment for cognate groups 4-7 had to remain
      tentative due to insufficient sequence variation. The number of zebrafish Hox
      fragments classified as members of cognate groups 1-4, 8, and 9 is identical to
      the number of genes in corresponding cognate groups of the mouse and human
      genomes. We found only two differences between the zebrafish and mouse Hox gene
      complement: four putative genes in group 10 (three in mammals) and only seven in
      the medial groups 5 to 7 (eight in mammals). Together with the previously
      published Hox gene sequences of the killifish, the larger number of zebrafish
      genes in group 10 is positive evidence for variation in the Hox gene complements
      among bony fish. In contrast, the Hox gene complement appears to be highly
      conserved among all tetrapods.

PMID- 8882498
TI  - Autoregulation of mariner transposase activity by overproduction and dominant
      negative complementation.
AB  - Genetic studies of the mariner transposable element Mos1 have revealed two novel
      types of regulatory mechanisms. In one mechanism, overproduction of the wild-type
      transposase reduces the overall level of transposase activity as assayed by the
      excision of a nonautonomous mariner target element. This mechanism is termed
      overproduction inhibition (OPI). Another mechanism is observed in a class of
      hypomorphic missense mutations in the transposase. In the presence of wild-type
      Mos1 transposase, these mutations exhibit dominant-negative complementation (DNC)
      that antagonizes the activity of the wild-type transposase. We propose that these
      regulatory mechanisms act at the level of the transposase protein subunits by
      promoting the assembly of oligomeric forms, or of mixed-subunit oligomers, that
      have reduced activity. We suggest that these regulatory mechanisms may apply
      generally to mariner-like elements (MLEs). Overproduction inhibition may help
      explain why the MLE copy number reaches very different levels in different
      species. Dominant-negative complementation may help explain why most naturally
      occurring copies of MLEs have been mutationally inactivated.

PMID- 8882499
TI  - Molecular evolution of ependymin and the phylogenetic resolution of early
      divergences among euteleost fishes.
AB  - The rate and pattern of DNA evolution of ependymin, a single-copy gene coding for
      a highly expressed glycoprotein in the brain matrix of teleost fishes, is
      characterized and its phylogenetic utility for fish systematics is assessed. DNA
      sequences were determined from catfish, electric fish, and characiforms and
      compared with published ependymin sequences from cyprinids, salmon, pike, and
      herring. Among these groups, ependymin amino acid sequences were highly divergent
      (up to 60% sequence difference), but had surprisingly similar hydropathy profiles
      and invariant glycosylation sites, suggesting that functional properties of the
      proteins are conserved. Comparison of base composition at third codon positions
      and introns revealed AT-rich introns and GC-rich third codon positions,
      suggesting that the biased codon usage observed might not be due to mutational
      bias. Phylogenetic information content of third codon positions was surprisingly
      high and sufficient to recover the most basal nodes of the tree, in spite of the
      observation that pairwise distances (at third codon positions) were well above
      the presumed saturation level. This finding can be explained by the high
      proportion of phylogenetically informative nonsynonymous changes at third codon
      positions among these highly divergent proteins. Ependymin DNA sequences have
      established the first molecular evidence for the monophyly of a group containing
      salmonids and esociforms. In addition, ependymin suggests a sister group
      relationship of electric fish (Gymnotiformes) and Characiformes, constituting a
      significant departure from currently accepted classifications. However,
      relationships among characiform lineages were not completely resolved by
      ependymin sequences in spite of seemingly appropriate levels of variation among
      taxa and considerably low levels of homoplasy in the data (consistency index =
      0.7). If the diversification of Characiformes took place in an "explosive"
      manner, over a relatively short period of time this pattern should also be
      observed using other phylogenetic markers. Poor conservation of ependymin's
      primary structure hinders the design of efficient primers for PCR that could be
      used in wide-ranging fish systematic studies. However, alternative methods like
      PCR amplification from cDNA used here should provide promising comparative
      sequence data for the resolution of phylogenetic relationships among other basal
      lineages of teleost fishes.

PMID- 8882500
TI  - Molecular evolution of the 5'-flanking regions of the duplicated Amy genes in
      Drosophila melanogaster species subgroup.
AB  - The nucleotide sequences of the 5'-flanking regions of the duplicated Amy genes
      in eight sibling species belonging to the melanogaster species subgroup are
      analyzed. In Drosophila melanogaster, a region of about 450 bp immediately
      upstream of the translation initiation site of the two paralogous genes (the
      proximal and distal genes) has sequence similarities. However, we could not
      detect any significant sequence similarity in the region more upstream than -450.
      This result indicates that the coding regions of the ancestral Amy gene were
      duplicated together with 450 bp of the 5'-flanking region as one unit. Multiple
      alignment of these 450-bp sequences in the proximal and distal genes of all eight
      species revealed a mosaic pattern of highly conserved and divergent regions. The
      conserved regions included almost all the putative regulatory elements identified
      in previous analyses of the sequences. A phylogenetic analysis of the aligned
      sequences shows that these 450-bp sequences are clustered into the proximal and
      the distal groups. As a whole, the divergence between groups in this region is
      very large in contrast to that in the coding regions. Based on the divergence
      between groups, the 450-bp region is divided into two subregions. We found that
      the ratios of the divergence between groups to that within groups differ in the
      two subregions. From these observations, we discuss a possibility of positive
      selection acting on the subregion immediately upstream of the Amy coding region
      to cause divergence of regulatory elements of the paralogous genes.

PMID- 8882501
TI  - A stepwise algorithm for finding minimum evolution trees.
AB  - A stepwise algorithm for reconstructing minimum evolution (ME) trees from
      evolutionary distance data is proposed. In each step, a taxon that potentially
      has a neighbor (another taxon connected to it with a single interior node) is
      first chosen and then its true neighbor searched iteratively. For m taxa, at most
      (m-1)!/2 trees are examined and the tree with the minimum sum of branch lengths
      (S) is chosen as the final tree. This algorithm provides simple strategies for
      restricting the tree space searched and allows us to implement efficient ways of
      dynamically computing the ordinary least squares estimates of S for the
      topologies examined. Using computer simulation, we found that the efficiency of
      the ME method in recovering the correct tree is similar to that of the neighbor
      joining method (Saitou and Nei 1987). A more exhaustive search is unlikely to
      improve the efficiency of the ME method in finding the correct tree because the
      correct tree is almost always included in the tree space searched with this
      stepwise algorithm. The new algorithm finds trees for which S values may not be
      significantly different from that of the ME tree if the correct tree contains
      very small interior branches or if the pairwise distance estimates have large
      sampling errors. These topologies form a set of plausible alternatives to the ME
      tree and can be compared with each other using statistical tests based on the
      minimum evolution principle. The new algorithm makes it possible to use the ME
      method for large data sets.

PMID- 8882502
TI  - A nuclear gene for higher level phylogenetics: phosphoenolpyruvate carboxykinase
      tracks mesozoic-age divergences within Lepidoptera (Insecta).
AB  - The sequence of phosphoenolpyruvate carboxykinase (PEPCK) has been previously
      identified as a promising candidate for reconstructing Mesozoic-age divergences
      (Friedlander, Regier, and Mitter 1992, 1994). To test this hypothesis more
      rigorously, 597 nucleotides of aligned PEPCK coding sequence (approximately 30%
      of the coding region) were generated from 18 species representing Mesozoic-age
      lineages of moths (Insecta: Lepidoptera) and outgroup taxa. Relationships among
      basal Lepidoptera are well established by morphological analysis, providing a
      strong test for the utility of a gene which has not previously been used in
      systematics. Parsimony and other phylogenetic analyses were conducted on
      nucleotides by codon positions (nt1, nt2, nt3) separately and in combination, and
      on amino acids, for comparison to the test phylogeny. The highest concordance was
      achieved with nt1 + nt2, for which one of two most-parsimonious trees was
      identical to the test phylogeny, and with all nucleotides when nt3 was down
      weighted sevenfold or higher, for which a single most-parsimonious tree identical
      to the test phylogeny resulted. Substitutions in nt3 approached saturation in
      many, but not all, pairwise comparisons and their exclusion or severe
      downweighting greatly increased the degree of concordance with the test
      phylogeny. Neighbor-joining analysis confirms this finding. The utility of PEPCK
      for phylogenetics is demonstrated over a time span for which few other suitable
      genes are currently available.

PMID- 8882503
TI  - Bootstrap method of interior-branch test for phylogenetic trees.
AB  - Statistical properties of the bootstrap test of interior branch lengths of
      phylogenetic trees have been studied and compared with those of the standard
      interior-branch test in computer simulations. Examination of the properties of
      the tests under the null hypothesis showed that both tests for an interior branch
      of a predetermined topology are quite reliable when the distribution of the
      branch length estimate approaches a normal distribution. Unlike the standard
      interior-branch test, the bootstrap test appears to retain this property even
      when the substitution rate varies among sites. In this case, the distribution of
      the branch length estimate deviates from a normal distribution, and the standard
      interior-branch test gives conservative confidence probability values. A simple
      correction method was developed for both interior-branch tests to be applied for
      testing the reliability of tree topologies estimated from sequence data. This
      correction for the standard interior-branch test appears to be as effective as
      that obtained in our previous study, though it is much simpler. The bootstrap and
      standard interior-branch tests for estimated topologies become conservative as
      the number of sequence groups in a star-like tree increases.

PMID- 8882504
TI  - Zea systematics: ribosomal ITS evidence.
AB  - Ribosomal internal transcribed spacer (ITS) sequences were used to evaluate the
      phylogenetics of Zea and Tripsacum. Maximum likelihood and polymorphism parsimony
      were used for phylogenetic reconstructions. Zea ITS nucleotide diversity was high
      compared to other plant species, but approximately equivalent to other maize
      loci. Coalescence of ITS alleles was rapid relative to other nuclear loci;
      however, there was still much diversity within populations. Zea and Tripsacum
      form a clade clearly differentiated from all other Poaceae. Four Zea ITS
      pseudogenes were identified by phylogenetic position and nucleotide composition.
      The phylogenetic position of Z. mays ssp. huehuetenangensis was clearly
      established as basal to the other Z. mays. The ITS phylogeny disfavored a Z.
      luxurians and Z. diploperennis clade, which conflicted with some previous
      studies. The introgression of Z. mays alleles into Z. perennis and Z.
      diploperennis was also established. The ITS data indicated a near contemporary
      divergence of domesticated maize and its two closest wild relatives.

PMID- 8882505
TI  - Zea ribosomal repeat evolution and substitution patterns.
AB  - Zea and Tripsacum nuclear ribosomal internal transcribed spacer (ITS) sequences
      were used to evaluate patterns of concerted evolution, rates of substitutions,
      patterns of methylation-induced deamination, and structural constraints of the
      ITS. ITS pseudogenes were identified by their phylogenetic position, differences
      in nucleotide composition, extensive deamination at ancestral methylation sites,
      and substitutions resulting in low-stability secondary RNA structures. Selection
      was important in shaping the kinds of polymorphisms and substitutions observed in
      the ITS. ITS substitution rates were significantly different among the Zea taxa.
      Deamination of cytosines at methylation sites was a potent mutation source, but
      selection appeared to maintain high methylation site density throughout the
      ribosomal repeat except for the gene promoter. Nucleotide divergence statistics
      identified selectively constrained regions at the 5' ends of the ITS1 and ITS2.

PMID- 8882506
TI  - Oxygen equilibria of cathodic eel hemoglobin analysed in terms of the MWC model
      and Adair's successive oxygenation theory.
AB  - Allosteric effects of erythrocytic NTP and proton concentrations on cathodic eel
      Hb were investigated by precise measurement of Hb-O2 equilibria (including
      extreme saturation values) and analysis in terms of the MWC two-state model and
      the Adair four-step oxygenation theory. Stripped cathodic Hb shows a reverse Bohr
      effect and high sensitivities to ATP and GTP that extend to high pH values (>
      8.5). A decrease in pH raises KT and lowers the allosteric constant L, compared
      to opposite effects in 'normal' Bohr effect Hbs. Phosphates even at low
      concentrations (GTP/Hb = 0.5) annihilate the reverse Bohr effect. GTP exerts a
      greater effect than ATP due to greater changes in KT and L, and NTP slightly
      reduces KR. In the absence of NTP, about 1.1 protons are released on
      deoxygenation at pH 8.15 (where most protons are released), indicating a pK value
      of the reverse Bohr group of approximately 8.2 (higher in oxy-Hb and lower in
      deoxy-Hb). The pH and NTP dependence of the Adair association constants and
      calculated fractional populations of Hb molecules in different oxygenation stages
      show that NTP effectors stabilise the T structure and postpone the T-R
      transition, whereas protons in the absence of NTP have the opposite effect. A
      molecular mechanism for the reverse Bohr effect is suggested.

PMID- 8882507
TI  - Effects of angiotensin II and its blockers Sar1-Ile8-angiotensin II and DuP 753
      on drinking in ducks in relation to properties of subfornical organ neurons.
AB  - Properties of systemically applied angiotensin II in stimulating water intake of
      normally hydrated ducks were studied and the results compared with properties of
      angiotensin II-responsive neurons of the subfornical organ which are considered
      as targets for circulating angiotensin II acting as a dipsogen. Following
      intravenous infusion of hypertonic saline (2000 mosmol.kg-1 at 0.3 ml.min-1 for 1
      h), intravenous infusion of 0.3 ml.min-1 isotonic saline with angiotensin II (200
      ng.min-1), starting 1 h later, stimulated drinking in each case at an angiotensin
      II plasma level of about 1400 pg.ml-1. Without hypertonic priming, the same
      angiotensin II infusion did not stimulate drinking in each experiment; however,
      if effective, repeated infusions of ANGII induced stable dipsogenic responses.
      Angiotensin II infusions did not alter plasma levels of antidiuretic hormone.
      Sar1-Ile8-angiotensin II, a non-selective angiotensin II antagonist, acted weakly
      as a partial agonist when infused at a dose 200-fold higher than angiotensin II
      and effectively blocked the dipsogenic action of angiotensin II; this corresponds
      to the inhibition of angiotensin II-induced excitation by Sar1-Ile8-angiotensin
      II observed in duck subfornical organ neurons. DuP 753 (losartan), an angiotensin
      II antagonist specifically blocking AT1 receptors in mammals, had equivocal
      effects on angiotensin II-induced drinking in ducks at rates 50- and 200-fold
      higher than angiotensin II, which corresponds to the weak inhibitory action of
      this compound on angiotensin II-induced neuronal excitation in the duck SFO.
      Blood pressure was only marginally elevated by the applied angiotensin II dose
      and Sar1-Ile8-angiotensin II had no effect.

PMID- 8882508
TI  - Vasotocin acts as a dipsogen in ducks at concentrations stimulating subfornical
      organ neurons in vitro.
AB  - The effects of systemic infusions of the avian antidiuretic hormone arginine
      vasotocin on water intake of domestic ducks were investigated under steady
      conditions of water balance in which angiotensin II was effective as a dipsogen.
      The study proceeded from the consistent stimulatory effect of arginine vasotocin
      on angiotensin II-responsive neurons found in the subfornical organ of ducks,
      suggesting brain-intrinsic vasotocinergic control of these neurons which are also
      accessible to circulating agents because of the lacking blood-brain barrier.
      Levels of circulating arginine vasotocin of about 2700 pg.ml-1 which were close
      to the threshold for activation of subfornical organ neurons in vitro, induced
      weak but significant drinking responses. Even at this high arginine vasotocin
      level circulatory effects were absent, thereby excluding their interference with
      water intake. Arginine vasotocin plasma levels of about 60 pg.ml-1 significantly
      attenuated the dipsogenic action of angiotensin. While drinking in response to
      high pharmacological levels of arginine vasotocin is assumed to mimic a
      stimulatory innervation of angiotensin-responsive subfornical organ neurons by
      brain-intrinsic vasotocinergic axons, attenuation of angiotensin-induced drinking
      by high physiological arginine vasotocin levels cannot be explained by its action
      on central neurons, but may be secondary to body fluid retention caused by the
      antidiuretic action of arginine vasotocin.

PMID- 8882509
TI  - Stratification and age-related differences in blubber fatty acids of the male
      harbour porpoise (Phocoena phocoena).
AB  - Fatty acid composition of blubber was determined at four body sites of 19 male
      harbour porpoises. A total of 65 fatty acids were quantified in each sample. The
      array of fatty acids contained in harbour porpoise blubber was similar to those
      found in other marine mammals. While chemical composition of total blubber was
      uniform over the body, with the exception of the caudal peduncle, vertical
      stratification was evident between the deep (inner) and superficial (outer)
      blubber layers. Fatty acids with chain lengths shorter than 18 carbons were
      present in significantly greater amounts in the outer blubber layer, while the
      longer-chain unsaturated fatty acids were more prevalent in the inner layer. This
      distribution suggests that the inner blubber layer is more active metabolically
      than the outer layer in terms of lipid deposition and mobilization. The degree of
      stratification between the two layers appears to increase with age, indicating a
      predictable turnover in the blubber layer of male porpoises. Harbour porpoise
      blubber contained high levels (2-27%) of isovaleric acid in the outer blubber
      layer, and these levels were positively correlated with age.

PMID- 8882510
TI  - Mediation of serotonin-induced hyperventilation via 5-HT3-receptor in European
      eel Anguilla anguilla.
AB  - The effects of serotonin (5-hydroxytryptamine) on ventilation were investigated
      by continuous measurements of intrabuccal pressure in unrestrained eel.
      Intravenous administration of 5-hydroxytryptamine (30 micrograms.kg-1) caused a
      large increase in ventilatory frequency (+ 100%) and amplitude (+ 140%). The 5
      hydroxytryptamine-induced hyperventilation was blocked by the 5-HT3-receptor
      antagonists metoclopramide (1.0 mg.kg-1) or MDL72222 (1.0 mg.kg-1), and was
      insensitive to the 5-HT1/2-receptor antagonist methysergide (3.0 mg.kg-1) and to
      the 5-HT4-receptor antagonist DAU 6285 CL (3.0 mg.kg-1). The hyperventilatory
      response to 5-hydroxytryptamine could be mimicked by the 5-HT3 receptor agonist 1
      phenylbiguanide (300 micrograms.kg-1). These results strongly implicate the 5-HT3
      receptor as the mediator of the 5-hydroxytryptamine-induced hyperventilation in
      eel.

PMID- 8882512
TI  - Modulation of catecholamine storage and release by the pituitary-interrenal axis
      in the rainbow trout, Oncorhynchus mykiss.
AB  - This study examined the effects of pituitary-interrenal hormones on catecholamine
      storage and release in the rainbow trout Oncorhynchus mykiss. An extract of trout
      pituitary elicited the release of adrenaline, but not noradrenaline, using an in
      situ perfusion preparation. A variety of doses of adrenocorticotropic hormone (2
      2000 mU) caused the release of both catecholamines in situ which was unaffected
      by pre-treatment with the ganglion blocker, hexamethonium, or the serotonergic
      receptor antagonist, methysergide, but was abolished in calcium-free media. Intra
      arterial injections of adrenocorticotrophic hormone in vivo caused an elevation
      of plasma adrenaline but not noradrenaline levels. Injections of cortisol in situ
      did not elicit catecholamine release. Trout given an intraperitoneal implant of
      cortisol (50 mg.kg-1 body weight) had significantly higher plasma cortisol
      concentrations when compared to controls after 7 days of implantation. Increases
      in the levels of stored catecholamines were observed in various regions of the
      kidney and posterior cardinal vein following 3 and 7 days of cortisol treatment.
      The ability of the chromaffin cells to release catecholamines in response to
      cholinergic stimulation was assessed in situ after 7 days of treatment. Basal
      (non-stimulated) adrenaline outflowing perfusate levels were greater in the
      cortisol-treated fish. Cortisol treatment increased the responsiveness of the
      catecholamine release process to low doses of the cholinoceptor agonist
      carbachol. Three or 7 days of cortisol treatment did not alter the in vitro
      activity of the enzyme phenylethanolamine-N-methyl transferase. The results of
      this study demonstrate that interactions within the pituitary-adrenal axis can
      influence both catecholamine storage and release in the rainbow trout.

PMID- 8882511
TI  - ETB-type receptors mediate endothelin-stimulated contraction in the aortic
      vascular smooth muscle of the spiny dogfish shark, Squalus acanthias.
AB  - Using various agonists, and the specific antagonist BQ-123, we have examined the
      sensitivity to endothelin of the vascular smooth muscle of the ventral aorta of
      the spiny dogfish shark, Squalus acanthias. Human endothelin-1 produced
      significant contraction of isolated vascular smooth muscle rings, with an EC50 of
      10 nmol.l-1. The presence of an intact endothelium did not alter this response
      but the magnitude of the contraction was greater in rings with an intact
      endothelium. The response to 0.2 mumol.l-1 endothelin-1 was equivalent to that of
      0.1 mmol.l-1 acetylcholine, and significantly greater than that to 80 mmol.l-1
      KCl, suggesting high sensitivity even to the heterologous, mammalian peptide. The
      Hill plot of the contractile response was a straight line with a slope of 1.12,
      indicating that a single receptor was mediating the response. Endothelin-1,
      endothelin-3, and sarafotoxin S6c produced similar concentration-response curves,
      and the response to endothelin-1 was insensitive to the ETA-specific inhibitor BQ
      123. Our data are consistent with the hypothesis that the receptor involved in
      the contractile response to endothelin of shark aortic vascular smooth muscle is
      of the ETB-rather than the ETA-type.

PMID- 8882514
TI  - Non-viral gene transfer: applications in developmental biology and gene therapy.
AB  - The main limitation of non-viral gene transfer methods is their relatively low
      efficiency in vivo. However, a number of approaches can be taken to improve their
      performances, whether the aim is studying gene function during development or
      employing these techniques for gene therapy. Three non-viral delivery systems
      that we have been particularly involved in in developing are described: the
      cationic lipid, dioctadecylamidoglycylspermine (DOGS), the cationic polymer
      polyethylenimine (PEI) and free DNA. The application of each of these methods to
      different in vivo situations is presented: the use of DOGS for transfecting
      embryos and the developing mammalian nervous system; the recent application of
      PEI to the nervous system; and how naked DNA can be employed for transfecting
      different muscles and brain. The relative efficiencies are compared on the basis
      of luciferase reporter gene expression assessed in each tissue with the most
      appropriate vector system. Finally, the perspectives for constructing composite
      vectors combining safety and efficiency are considered briefly.

PMID- 8882513
TI  - Rhythmic melatonin secretion in different teleost species: an in vitro study.
AB  - The rhythmic production of melatonin is governed by intrapineal oscillators in
      all fish species so far investigated except the rainbow trout. To determine
      whether the latter represents an exception among fish, we measured in vitro
      melatonin secretion in pineal organs of nine wild freshwater and six marine
      teleost species cultured at constant temperature and under different photic
      conditions. The results demonstrate that pineal organs of all species maintain a
      rhythmic secretion of melatonin under light:dark cycles and complete darkness,
      and strongly suggest that most fish possess endogenous intrapineal oscillators
      driving the rhythm of melatonin production, with the exception of the rainbow
      trout.

PMID- 8882515
TI  - Response to denervation of rabbit soleus and gastrocnemius muscles. Time-course
      study of postnatal changes in myosin isoforms, fiber types, and contractile
      properties.
AB  - In contrast to general belief, the response of rabbit muscles to denervation is
      maturation to slow-like type muscles [7]. We report now an investigation by
      biochemical, morphological, and mechanical studies of the time course effects of
      muscle denervation on the slow-type soleus and fast-type gastrocnemius to help
      elucidate the mechanism of maturation of rabbit denervated muscles to slow-like
      muscles. In both muscles, denervation induced selective progressive atrophy of
      most fast fibers and hypertrophy of many slow fibers which displayed wide Z
      lines; this was accompanied by the appearance of hybrid LC1F- and LC1E-associated
      slow myosins. The percentage of slow myosins increased with age similarly in the
      contralateral and denervated soleus. On the other hand, the percentage of slow
      myosins remained low in the contralateral gastrocnemius, whereas it increased to
      95% in the denervated gastrocnemius; in the denervated gastrocnemius, the
      percentage of slow myosins reached 50% at about 35 days postnatal. At this age,
      the maximal shortening velocity of the denervated gastrocnemius and its twitch
      contraction time were already those of a slow-type muscle. This suggests that in
      addition to myosin, other proteins contributed to the mechanical properties of
      the denervated gastrocnemius. Transformation of rabbit denervated muscles to slow
      like type muscles, which are associated with a lower energy requirement and
      higher muscle endurance than fast-type muscles, may constitute an adequate model
      for human neuromuscular pathology.

PMID- 8882516
TI  - Research on polychaete annelid osmoregulatory peptide(s) by immunocytochemical
      and physiological approaches. Computer reconstruction of the brain and evidence
      for a role of angiotensin-like molecules in Nereis (Hediste) diversicolor OF
      Muller.
AB  - Immunohistochemical and physiological studies were carried out on Nereis
      (Hediste) diversicolor OF Muller in order to obtain evidence concerning the
      neuroendocrine control of polychaete osmoregulation. The occurrence in this
      animal of peptides immunologically related to mammalian angiotensin II and I (AII
      and AI) and oxytocin (OT) was demonstrated in the brain and the ventral nerve
      cord (VNC) perikarya and nerve fibres as well as in a few peripheral structures
      (peripheral nerves, epithelial cells, nuchal organ, intestine and nephridia). The
      exact localization of immunoreactive cells was achieved by serial sections of
      brain and ventral nerve cord followed by a three-dimensional reconstruction of
      brain ganglionic nuclei using the CATIA ('Conception Assistee Tridimensionnelle
      Inter Active') Dassault system program. Injections of polyclonal antisera against
      AII or OT provoked a partial inhibition of the increase in body weight in Nereis
      exposed to hypo-osmotic medium. The effect of a-AII seemed more pronounced than
      that of a-OT. In a subsequent test, injections of synthetic AII and AII-amide
      (peptide recently isolated from an achaete (Salzet et al (1995) J Biol Chem 270,
      1575-1582) enhanced the increase in body weight and, therefore, strengthened the
      hypothesis of the neuroendocrine control of Nereis osmoregulation. The
      antidiuretic effect of both synthetic peptides in this study was indicative of
      the exact role of Nereis endogenous molecule(s). AII was less potent than its
      amidated form. If AI-like can easily be struck off the list of putative
      endogenous osmoregulatory factors, the role of OT-like substance in Nereis
      osmoregulation, which is partially demonstrated in this study, needs to be
      clarified by further physiological experiments using injection of synthetic
      peptide(s) or endogenous substance(s). All these results are discussed and
      compared to those recently obtained in an achaete annelid (Salzet et al (1993)
      Brain Res 631, 247-255; Salzet et al (1993) Brain Res 601, 173-184; Salzet et al
      (1995) J Biol Chem 270, 1575-1582.

PMID- 8882517
TI  - Partial characterization of eosinophilic granule cells (EGCs) and identification
      of mast cells of the intestinal lamina propria in rainbow trout (Oncorhynchus
      mykiss). Biochemical and cytochemical study.
AB  - The role of intestinal eosinophilic granule cells (EGCs) is still a subject of
      discussion. The aim of this study was to obtain additional functional data for a
      better characterization of these cells. Biochemical studies indicated the
      presence of small amounts of histamine, a characteristic and consistent marker of
      mast cells, in the posterior gut. On the other hand, histamine is always absent
      from homogenates of isolated EGCs. Using colorimetric assays, we were able to
      show aryl sulphatase B activity (18.5 +/- 3.7 nM nitrocatechol/10(6) cells) and
      detected peroxidase (1.86 +/- 0.03 ng/10(6) cells) in EGC homogenates. A
      cytochemical study enabled us to localize peroxidase in the granules of EGCs.
      These cells can also phagocytose latex beads. EGCs should thus be considered as
      homologous with mammalian eosinophils and not with mast cells. The screening for
      cells in the mucosae containing chondroitin sulphate revealed sparsely
      represented cells in the loose connective tissue in immediate proximity to blood
      capillaries. These cells could be mucosal mast cells.

PMID- 8882518
TI  - Transverse-axial tubular system in guinea pig ventricular cardiomyocyte: 3D
      reconstruction, quantification and its possible role in K+ accumulation-depletion
      phenomenon in single cells.
AB  - K+ accumulation-depletion (AD) phenomena were found in single guinea pig
      ventricular myocytes using the patch-clamp method in whole cell configuration. We
      suggest that the cardiomyocyte transverse-axial tubular system (TATS) lumen is
      the restricted extracellular space where the K+ AD could take place. A three
      dimensional (3D) reconstruction of the TATS in a cardiomyocyte segment from
      serial ultrafine sections was made by three-dimensional isosurface rendering and
      quantitative data were obtained from the image processing. This original approach
      of the TATS intricated network gave a new vision of this membrane system;
      moreover, quantitative data about the tubular membrane importance (52.6% of the
      total plasma membrane) and its surface area versus the tubular volume fraction
      (STATS/VTATS = 13.5 micron 2/micron 3) would fit in the electrophysiological
      results. The hypothesis whereby this 'extracellular' compartment could play, in
      single cells, a role as important as that of narrow clefts in the whole heart is
      discussed.

PMID- 8882519
TI  - The loss of contact inhibition and anchorage-dependent growth are key steps in
      the acquisition of Listeria monocytogenes susceptibility phenotype by non
      phagocytic cells.
AB  - We have previously demonstrated that intestinal and kidney finite cell lines were
      resistant to L monocytogenes invasion (ie allowed low bacterial entry and no
      intracellular multiplication) in contrast to the continuous cell lines which were
      susceptible to Listeria invasion (ie allowed high bacterial entry and
      intracellular multiplication) (Velge et al (1994a) Med Microbial Immunol 183,
      145). The aim of this study was to discover whether epigenetic or genetic
      cellular modifications could convert L monocytogenes resistant cells into a
      susceptible phenotype and to determine the cellular steps involved in Listeria
      susceptibility. Among the 5-azacytidine treated finite cell lines, the
      untransformed immortal cell lines established remained resistant to L
      monocytogenes invasion whereas the weakly transformed continuous cell lines
      established were converted into a susceptible phenotype. Transfection of
      resistant cells by SV40 large T antigen induced only highly transformed
      continuous cell lines displaying a susceptible phenotype. Taken together these
      data show that cell transformation enhanced Listeria invasion. This conclusion
      was supported by the observation that L monocytogenes was able to induce cell
      foci within murine finite cell monolayers. This morphological cell transformation
      was completely reversible and required live bacteria inside cells. In conclusion,
      we may speculate that the L monocytogenes intracellular multiplication observed
      within cell foci could be explained by the loss of contact inhibition of the
      finite cell monolayer. Indeed, the loss of both contact inhibition and anchorage
      dependent growth are the key steps involved in the L monocytogenes susceptibility
      phenotype.

PMID- 8882520
TI  - Presence of Chromatium vinosum chaperonins 10 and 60 in mitochondria and
      peroxisomes of rat hepatocytes.
AB  - In the present study we report the occurrence of chaperonins, cpn10 and cpn60, in
      Chromatium vinosum and rat hepatocytes, using specific polyclonal antibodies in
      conjunction with the protein A-gold immunocytochemical technique. As demonstrated
      by quantitative evaluations, the immunolabeling for cpn10 and cpn60 in C vinosum
      cells was associated primarily with the bacterial cell envelope. In rat liver
      homogenates, Western immunoblotting analysis has shown that antibodies to cpn10
      from C vinosum recognize an unique 25-kDa protein that remains to be further
      characterized. On the other hand, the antibody to cpn60 from C vinosum revealed
      the presence of a 60-kDa protein in the rat liver homogenates. Immunofluorescence
      on rat liver tissue revealed an intracellular granular labeling for both
      chaperonins. On the other hand, using the post-embedding immunoelectron
      microscopy technique cpn10 and cpn60 were localized specifically in liver
      mitochondria and peroxisomes. Interestingly, further analysis of the labeling
      distribution confirmed the association of both proteins with the mitochondrial
      inner membrane whereas in the peroxisomes the chaperonins appeared to be located
      in the matrix, away from the limiting peroxisomal membrane. The colocalization of
      both chaperonins suggests that, as in other bacteria as well as eukaryotic cells,
      they may act in tandem for the proper folding of particular proteins.

PMID- 8882521
TI  - A human autoantibody recognizing nuclear matrix-associated nuclear protein
      localized in dot structures.
AB  - A human autoimmune serum is used to characterize a protein which is located
      within a dot-like structure of the interphase nucleus. The dots are located in
      the nucleoplasma outside the nucleoli. The dot-like structure could be observed
      on a variety of human substrates (HEp-2, HepG2, HeLa, Molt-4, WI-38 cell lines,
      peripheral blood lymphocytes), mouse cell lines and tissues (3T3, L929, spleen
      sections), rat sections, marsupial PtK2 cells and hamster cell lines. The range
      of the number of dots and their size differed between cells and cell lines and
      varied between 1 and 24. The antigen could be identified as a 53 kDa protein with
      a pI of 8.7 and was named NDP53. Digestion experiments suggested that the protein
      is not associated with DNA or RNA, but is associated with the nuclear matrix.
      Immunelectron microscopy using ultra-thin sections revealed filamentous
      structures with a diameter of 0.1 to 0.6 microns. The antigen colocalizes with
      Sp100, PML and NDP55, which are part of a multiprotein complex known as PML
      oncogenic domain (POD), nuclear bodies, Kr bodies or ND10.

PMID- 8882522
TI  - Cytokines and invertebrate immune responses.
AB  - A profound interrelationship between cytokines and invertebrate (molluscs) immune
      responses has been reported. Different cytokines (IL-1 alpha, IL-2 and TNF-alpha)
      significantly stimulate molluscan hemocyte motility, increasing phagocytic
      activity and provoking the induction of nitric oxide synthase. As far as cell
      motility is concerned, the response to different cytokines varied between
      species. These and other recently reported findings (Ottaviani et al (1994) FEBS
      Lett 351, 19-21; Ottaviani et al (1995) Biochem Biophys Res Commun 207, 288-292)
      suggest that cytokines are important, ancestral, and functionally conserved
      molecules, which have also maintained their pleiotropicity, redundancy in the
      mode of action, and high promiscuity of their receptors during evolution.

PMID- 8882524
TI  - Intensivists in Singapore: raison d'etre in the modern era of critical care
      medicine.

PMID- 8882523
TI  - Cytological events during the initiation of meristematic nodules in calli derived
      from eggplant protoplasts.
AB  - Histological and ultrastructural studies have been undertaken in order to
      identify the particularities and, if possible, some mechanisms involved in
      regeneration from protoplasts in the eggplant Solanum melongena. The most
      important result consists of a peculiar and concomitant association of
      meristematic and differentiated features only in cells from which regenerative
      processes originate.

PMID- 8882525
TI  - Eclampsia--no room for complacency.

PMID- 8882526
TI  - Pregnancy and diabetes.

PMID- 8882527
TI  - Percutaneous balloon valvuloplasty in mitral restenosis after previous surgical
      commissurotomy.
AB  - OBJECTIVES: The aim of this study was to determine the safety profile, mitral
      valve outcome and follow-up functional status after percutaneous balloon mitral
      valvuloplasty (PBMV) in patients with mitral restenosis post-surgical
      commissurotomy. METHODS: Sixteen patients with symptomatic mitral restenosis
      after previous surgical commissurotomy underwent valvuloplasty using the Inoue
      balloon stepwise dilatation method. Echocardiography was performed before and
      after the procedure to evaluate the mitral valve area. RESULTS: All procedures
      were successfully completed without cardiac perforation, thromboembolism,
      resultant severe mitral regurgitation or death. The mitral valve area improved
      from 0.9 +/- 0.2 to 1.6 +/- 0.3 (p = 0.0001), accompanied by a significant
      immediate reduction in the left atrial pressure and transmitral gradient.
      Compared with PBMV in patients without past mitral surgery, patients with mitral
      restenosis undergoing PBMV experienced less valve area improvement but the
      difference was not significant (p = 0.137). Optimal valve enlargement resulting
      in mild mitral stenosis was achieved in 12 of the 16 patients. Midterm
      symptomatic benefit was observed in almost all patients. CONCLUSIONS: In view of
      the excellent success rate, low complication risk, the optimal haemodynamic
      results and favourable functional outcome afforded by mitral balloon
      valvuloplasty in patients with mitral restenosis after prior surgical
      commissurotomy, it is logical that balloon mitral valvuloplasty, where available,
      should be the initial treatment modality in this group of patients with suitable
      valve morphology before considering repeat mitral surgery.

PMID- 8882528
TI  - Clinical utility, safety, acceptability and complications of transoesophageal
      echocardiography (TEE) in 901 patients.
AB  - Transoesophageal echocardiography (TEE) has earned an important role in the
      evaluation of patients with cardiovascular diseases. We report our TEE experience
      in 901 patients who had suboptimal transthoracic echocardiographic studies
      performed between September 1989 and June 1993. The patient-population consisted
      of 459 females and 442 males, with an ethnic distribution of Chinese 76.5%,
      Malays 12.7%, Indians 8.5% and Others 2.3%. The mean age was 48 years. The main
      indications for TEE were: cardiac source of embolism (27.5%); native valve
      pathology (19.1%); atrial septal abnormality (9.7%); infective endocarditis
      (8.3%); intracardiac masses (7.0%); prosthetic valve dysfunction (6.3%);
      congenital heart diseases (4.6%); aortic diseases (3.4%) and miscellaneous
      (14.1%). The majority of the studies were done on in- and out-patients, with only
      1.2% performed in the intensive care area and 1% intraoperatively. 82.6% of TEE
      intubation were accomplished within one minute and most of the TEE studies were
      completed within twenty minutes. There were ten failures (1.2%). Major
      complications occurred in 5 patients (0.6%) but there was no mortality. 90.5% of
      the studies were considered by the operators as additionally-informative or
      useful for clinical decision making. In a subgroup analysis, 90.6% of the
      patients who had undergone TEE indicated their willingness for repeat studies if
      required and TEE was able to increase the sensitivity of detecting a potential
      cardioembolic source from 10.3% to 29.5%. In conclusion, with increasing
      experience, TEE can be performed expeditiously and safely, with good
      acceptability by our local population. TEE provides useful or additional
      information that supplements standard transthoracic echocardiography in a wide
      ranging spectrum of cardiac conditions.

PMID- 8882529
TI  - Evaluation of the efficacy of sequential intravenous-oral administration of
      pefloxacin in community-acquired lower respiratory tract infections in patients
      with underlying conditions.
AB  - We studied the efficacy of sequential intravenous-oral pefloxacin therapy in
      community-acquired lower respiratory tract infection in 24 patients with one or
      more underlying conditions. Twenty-eight patients were enrolled into the study
      but only 24 patients were evaluated. There were 16 males and 8 females with a
      mean age of 66.9 +/- 11.2 years (mean +/- SD, range 46 to 87 years). The
      underlying conditions present were bronchiectasis, chronic obstructive lung
      disease and diabetes mellitus. Patients who were older than 70 years but without
      any underlying condition were also enrolled. All received 4 days of intravenous
      pefloxacin 400 mg twice a day followed by oral pefloxacin 400 mg twice a day for
      another 10 days. Assessment of success was based on clinical, microbiological and
      radiological improvement. Pefloxacin produced 79.2% clinical cure rate. Another
      8.3% showed improvement. Pefloxacin was well tolerated. There were few adverse
      effects and none of the patients required a change of antibiotic. Pefloxacin was
      an effective and well tolerated treatment for respiratory tract infection and had
      the advantage of broad in-vitro antibacterial activity, twice daily dosing and
      sequential availability in an intravenous and oral formulation.

PMID- 8882530
TI  - Massive pleural effusion in pancreatitis: 2 case reports.
AB  - We report 2 patients with left-sided pleural effusion occurring in the setting of
      acute pancreatitis. Both patients had a strong history of alcohol consumption. In
      each case the pleural fluid amylase was markedly elevated, higher than that in
      the serum. The effusions resolved with closed chest tube drainage and the
      pancreatitis subsided with conservative therapy. In patients presenting with
      significant pleural effusions and acute upper abdominal symptoms, a thoracentesis
      with determination of the amylase titre may provide a quick means of diagnosing
      acute pancreatitis.

PMID- 8882531
TI  - Diagnosis of deep vein thrombosis using duplex ultrasonography.
AB  - Duplex ultrasonography is a safe, accurate, efficient, inexpensive, noninvasive
      diagnostic test for deep vein thrombosis (DVT). The sensitivity and specificity
      of this technique is comparable to venography in symptomatic patients in many
      studies. The diagnostic accuracy of this test can be further enhanced by serial
      studies. We report our experience with the use of this technique for study of 180
      patients with clinically suspected DVT. Only 55 (30.6%) patients were confirmed
      to have DVT on duplex ultrasonography which illustrates the inaccuracy of bedside
      diagnosis of this potentially life-threatening condition. Almost all our DVT
      patients have proximal vein involvement, indicating that venous thrombosis
      usually do not cause signs or symptoms until they become large, occlusive and
      extend into the proximal veins. It is also observed in our study cohort that half
      of the patients with proximal vein thrombosis has incomplete recanalisation on
      follow-up study. None of them with normal study developed significant sequelae of
      untreated DVT, suggesting that it is safe to withhold treatment based on result
      of this non-invasive test. Duplex ultrasonography is the diagnostic modality of
      choice for suspected DVT in symptomatic patients and is an excellent substitute
      for conventional contrast venography.

PMID- 8882532
TI  - Colonisation factors amongst clinical isolates of enterotoxigenic Escherichia
      coli.
AB  - The production of heat-labile (LT) and heat-stable (ST) enterotoxins,
      colonisation factor antigens (CFAs) and haemagglutinins was investigated amongst
      310 Escherichia coli (E. coli) isolates obtained from 62 children under the age
      of five, with diarrhoea. Twenty-one isolates were found to produce enterotoxins,
      of which fifteen (71%) isolates produced ST only, 2 (10%) produced LT only and 4
      (19%) produced both LT and ST. However, none of the isolates demonstrated any of
      the common CFAs identified to date, but 8 out of the 21 isolates demonstrated
      haemagglutination with rabbit, sheep or human group A erythrocytes, suggesting
      the presence of putative CFAs, yet unidentified.

PMID- 8882533
TI  - Obstetric outcome of pregestational diabetic pregnancies.
AB  - This retrospective study examined the obstetric and neonatal outcome in 23
      pregestational diabetic pregnancies. The incidence of congenital malformations
      and mortality in infants of diabetic mothers was increased compared to the
      control population. Late booking for antenatal care and poor glycaemia control
      are probably the reasons for this high incidence. There was also a significantly
      higher preterm delivery and Caesarean section rate in the pregnancies complicated
      by pregestational diabetes. The neonatal morbidity was also higher than the
      controls in terms of jaundice, hypoglycaemia, respiratory distress syndrome and
      admissions to neonatal intensive care unit. Only with preconception counselling
      and tight glycaemia control in the periconception period and throughout pregnancy
      can we expect a drop in the complication rates in pregestational diabetic
      pregnancies.

PMID- 8882534
TI  - Glycosylated haemoglobins in women with low risk for diabetes in pregnancy.
AB  - Glycosylated haemoglobin levels (HbA1) were determined in 489 normal pregnant
      Singaporean women, attending a diabetic screening programme using a 50g glucose
      challenge test. All subjects had no risk factors for diabetes mellitus nor a
      history of previous gestational diabetes. They were selected when the 1h 50g
      glucose challenge (GCT) is < 6.66 mmol/l or a 2h post-glucose level of < 7.77
      mmol/l (a 75g OGTT is repeated within a week of an abnormal GCT). Another 18
      subjects with normal OGTT but did not have a 50g glucose challenge done were also
      included in the study. Mean and normal range (2 SD) of HbA1 levels in all
      subjects were 4.64% and 3.66-5.62%, respectively. Mean HbA1 levels also varied
      with gestation and ethnic group. The HbA1 appeared to be low at early gestation
      with nadir at 21-24 weeks and thereafter returned to initial levels at term. In
      Chinese, mean HbA1 levels, random plasma glucose and 1h glucose challenge were
      significantly higher than those of the Malays but not the Indians. In referring
      to these levels, the variation within gestation and ethnic group must also be
      considered.

PMID- 8882535
TI  - Eclampsia--are we doing enough?
AB  - OBJECTIVES: This paper reviews the cases of eclampsia managed at the Kandang
      Kerbau Hospital with respect to incidence, management, maternal and perinatal
      outcome. METHOD: A retrospective analysis of eclampsia occurring over a 4-year
      period from January 1990 to December 1993. RESULTS: There were 27 cases of
      eclampsia among 59,599 deliveries during the study period, giving an overall
      incidence of 45.3 per 100,000 deliveries. Sixteen patients were nulliparous and
      the mean age was 29 years. Two-thirds of the cohort were booked patients and more
      than half of the cohort (55.6%) had their first seizure despite being in
      hospital. The majority (86.2%) of all seizures recorded occurred in the
      antepartum and intrapartum period. Eleven of the patients (40.7%) were
      asymptomatic prior to the first fit while headache was the commonest symptom of
      impending eclampsia in the remainder. Fifteen patients (55.6%) had significant
      proteinuria and this was associated with significant neonatal morbidity. The mean
      gestational age was 35.9 weeks and the mean birth weight was 2,328g. Major areas
      of substandard management included failure to administer anticonvulsant
      prophylaxis and antihypertensive agents when indicated, failure to assess for
      proteinuria, and failure to closely monitor the hypertensive and proteinuric
      patient. Seven patients developed convulsions despite anticonvulsant prophylaxis.
      Twenty-four patients were delivered by Caesarean section. There were 26 live born
      infants (singletons) and one abortus. There was no perinatal mortality. Neonatal
      morbidity was frequent and attributable to prematurity (51.9%) and birth asphyxia
      (29.6%). The majority of infants were well neurologically on long term follow-up.
      There was no maternal mortality but significant morbidity was present in 8
      patients (29.6%). High uric acid levels were associated with intrauterine death,
      prematurity and intrauterine growth retardation. Seven patients remained
      hypertensive on follow-up. Residual neurological deficits persisted in 3
      patients. CONCLUSIONS: The incidence of eclampsia at Kandang Kerbau Hospital
      shows an unsteady decline over the past 4 years. It carries significant foetal
      mortality (3.7%) as well as neonatal (74.1%) and maternal (29.6%) morbidity. The
      observation that neither the occurrence of antenatal office visits nor
      hospitalisation prevents eclampsia, and that substandard management was
      identified in most of the cases (77.8%) shows that there is no room for
      complacency and that more needs to be done. Improvement in patient assessment,
      institution of appropriate preventive therapy, a high index of suspicion even in
      apparently low-risk patients coupled with a disease notification system and
      regular audit may be the key strategies to reduce the incidence of this dreaded
      obstetric complication.

PMID- 8882536
TI  - Mass screening for diabetic retinopathy--a report on diabetic retinal screening
      in primary care clinics in Singapore.
AB  - INTRODUCTION: Mass screening for diabetic retinopathy is expensive and
      inaccessible if done by institutional ophthalmalogists. Most diabetics are seen
      in primary care. Hence it is logical to provide mass screening in primary care
      clinics. In Singapore, government polyclinics are ideal centres of screening as
      they are well organised and accessible to the community. SCREENING METHOD: An
      effective mass screening strategy must provide wide coverage, be low cost and
      have the ability to assess diabetic eyes accurately and quickly. Non-mydriatic
      fundal photography was used as the screening method. Mass coverage was achieved
      by rotating two cameras around six government polyclinics. Cost was reduced by
      training existing staff and organising the programme to provide a high turnover
      of screenees. The photographs were read by ophthalmologists in a government-owned
      hospital. Patients that required referral were referred to specialist eye
      clinics. RESULTS: A total of 13,296 patients were screened or rescreened during a
      period of 2 years (25 months). 2,911 patients or 21.8% of the total screened were
      found to have diabetic retinopathy. About half of these (10.8%) had sight
      threatening retinopathy. The most common sight threatening retinopathy was
      maculopathy (8.0%). Twenty-two percent of cases screened were referred. These
      include referral for other ocular conditions detected during the screening.
      CONCLUSION: Non-mydriatic fundal photography has proven to be both accessible and
      effective in screening diabetic eyes in urban Singapore and can be recommended
      for mass screening of diabetic eyes in the community.

PMID- 8882537
TI  - Laser reduction of inferior turbinates in children.
AB  - Perennial nasal obstruction in children refractory to medical treatment may be
      managed by turbinate reduction. Turbinectomy may involve a risk of significant
      postoperative bleeding and requires nasal packing. Submucosal diathermy is
      followed by nasal congestion and crusting; recurrent nasal obstruction is
      frequent at fifteen months. This study assesses the benefits of carbon dioxide
      laser reduction of inferior turbinates in 20 children. Intraoperative blood loss
      was negligible and no nasal packing was required. There was minimal postoperative
      discomfort which required no analgesia. No postoperative haemorrhage was
      recorded. The children were able to drink and eat by 4 and 6 hours respectively.
      Relief of nasal obstruction occurred one to seven days postoperatively and was
      confirmed by rhinohygrometry. Nasal patency was maintained on eighteen to twenty
      four months follow up. Mucosal healing was completed by four weeks. Mucosal
      saccharin clearances were normal postoperatively. We conclude laser turbinectomy
      is an excellent means of turbinate reduction in selected children.

PMID- 8882538
TI  - High frequency oscillatory ventilation in newborns with idiopathic persistent
      pulmonary hypertension.
AB  - Three consecutive term infants diagnosed as suffering from idiopathic persistent
      pulmonary hypertension of the newborn (PPHN) were tried on high frequency
      oscillatory ventilation (HFOV) after failure of conventional mechanical
      ventilation (CMV). All experienced a significant improvement in oxygenation. All
      three infants survived. HFOV was utilised in a fourth term infant initially
      diagnosed as having idiopathic PPHN with an immediate benefit. This infant
      subsequently died and was found at autopsy to have a lethal congenital
      maldevelopment of pulmonary microcirculation. No serious adverse effects were
      encountered with HFOV in contrast to the use of pharmacologic agents where
      hypotension was a serious problem. A therapeutic trial of HFOV is simple and
      efficient, and would not cause undue delay in the commencement of other rescue
      therapy should it prove unsuccessful. We predict HFOV will replace non-specific
      vasoactive agents as the standard first line alternative to CMV for the treatment
      of idiopathic PPHN.

PMID- 8882539
TI  - The presymptomatic molecular diagnosis of familial adenomatous polyposis in
      Singapore.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which
      predisposes to the development of colorectal cancer. The adenomatous polyposis
      coli (APC) gene, mutation of which is responsible for FAP, has been localised to
      chromosome 5q21. Linkage studies using DNA markers have proven useful for
      presymptomatic diagnosis of at-risk individuals. We have examined 8 FAP families
      from the Singapore Polyposis Registry by using 4 linked and 2 intragenic DNA
      markers. Presymptomatic diagnosis could be made in 84% (37 of 44) of at-risk
      individuals. Among these presymptomatically diagnosed cases, positive prediction
      was made in 32% (12 of 37) whereas negative prediction was possible in 68% (25 of
      37). As the accuracy of genetic diagnosis is high and the test reliable in most
      cases, the major impact of these tests will be the reduction of unnecessary
      anxiety and a significant reduction in the frequency of screening for at-risk
      individuals who are not carrying the affected gene.

PMID- 8882540
TI  - Bladder involvement in patients with colorectal carcinoma.
AB  - Twenty-seven patients underwent concomitant partial cystectomies out of a total
      of 542 patients with colorectal carcinoma operated on between October 1989 to
      December 1991. There were 19 males and 8 females with a median age of 63.7 years
      (range 44-80). The patients were followed up for a median of 40.2 months (range
      27-75 months). Histological invasion into the bladder was found in only 26% of
      the tumours. Eighty-five percent of the patients with carcinomatous invasion had
      preoperative urological symptoms whilst only 20% of those with inflammatory
      adhesions had urological symptoms. Four percent of the patient were Dukes' A, 50%
      Dukes' B, 42% Dukes' C and 4% Dukes' D. Twenty (74%) patients are alive without
      evidence of local or distant metastasis. One has local recurrence and another,
      distant metastasis. Five patients have died. The prognosis of patients with
      colorectal cancer and bladder involvement appears to be similar to those without
      bladder involvement provided clear margins are obtained.

PMID- 8882541
TI  - Outcome of the extremely low birth weight infants (less than 999 grams): what
      messages are we getting?
AB  - The outcome of the extremely low birth weight (less than 1,000g or ELBW) babies
      continues to improve. More ELBW babies are surviving, though some of them may
      have various degrees of impairment or disability. The chance of dying or
      surviving with a major disability or cerebral palsy declines significantly in
      recent years in the developed countries. The implication of these findings is
      that application of neonatal care does not increase the risk of disabled survival
      as has been often feared but promoted normal survival. Great effort has been put
      in to achieve good results and better outcome. Developing countries however, will
      face a problem of achieving similar results because of limited resources or
      priority of allocation of limited resources, inadequate facilities, lower socio
      economic status, poor home environment and lack of follow-up services, training
      and rehabilitation set-ups or intervention programme. What is the relevance of
      these good results in relation to the developing or third world countries? The
      limit of viability may have to be redefined. Nevertheless, it should be the aim
      to lower the mortality of these high risk babies and to reduce complications and
      morbidity of the survivors. Maintenance and control of body temperature, control
      of infections, blood sugar monitoring, antenatal steroids for the mother in
      premature labour, resuscitation at birth or even simple nasal continuous positive
      airway pressure (CPAP) should come a long way in fulfilling these goals. Those
      ELBW children who survive without neurological damage may have learning
      difficulties. It is necessary to find out the reasons for that such as the impact
      of the home environment on mental development. Do the children have a good
      background conducive for learning? Are there establishments for intervention
      programme in the community for these high risk children? The ratio of neonatal
      beds per 1,000 deliveries may have to be reviewed now that more ELBW infants are
      staying in the hospital for a longer period, and surviving.

PMID- 8882542
TI  - Current approach to the management of urinary stress incontinence.
AB  - The plethora of treatment modalities available for the treatment of female
      urinary stress incontinence reflects the uncertainty in the pathophysiology of
      this condition and the mechanism of cure. No single treatment method is suitable
      for all patients. For best results, many factors must be considered before
      choosing the treatment method most suited to the particular patient. This review
      examines the various treatment options available and attempts to set out criteria
      for choice of treatment. The role of conservative treatment has been deliberately
      highlighted especially for young and well motivated women with mild to moderate
      urinary stress incontinence before surgical treatment is used. The role and
      limitations of well established surgical procedures like Burch colposuspension
      and urethroplasty and the more recently introduced procedures like collagen
      implants, laparoscopic colposuspension and the role of artificial urinary
      sphincter are also examined.

PMID- 8882543
TI  - Management of hyperlipidaemia: postscript.

PMID- 8882544
TI  - Community-acquired pneumonia.
AB  - Major changes have occurred in the epidemiology of community-acquired pneumonia
      recently. The emergence of new pathogens emphasises the need for continued
      vigilance in the diagnosis of pneumonia while changes in the microorganism or in
      the host have resulted in exciting new aspects of several old pathogens. Clinical
      and radiologic signs are unreliable in predicting the infecting organisms. Thus
      initial therapy is nearly always empiric. This approach often requires good
      clinical judgement and a knowledge of local epidemiological patterns in choosing
      an appropriate regimen. State-of-the-art invasive diagnostic procedures are
      usually reserved for pneumoniae that fail to resolve with initial treatment. Non
      specific measures like stabilisation of underlying medical conditions, adequate
      nutrition and cessation of smoking or alcohol may help prevent the development of
      community-acquired pneumonia. On a larger scale, influenza and pneumococcal
      vaccinations are cost-effective preventive measures.

PMID- 8882545
TI  - Understanding HIV disease.
AB  - The world is now facing the second decade of global epidemic of HIV infection.
      Most of the Asian countries including Singapore are seeing a trend of rapid
      increase of HIV infected cases each year. It is now known that the HIV disease
      has a prolonged asymptomatic period of several years before the onset of AIDS
      defining illness. A HIV-infected person may present to a physician at any point
      of the entire course of HIV infection. Hence, this article aims to give an
      overview of HIV disease and to provide information for doctors today to equip
      themselves with adequate knowledge to deal with this deadly infection.

PMID- 8882546
TI  - Differential diagnosis of electrocardiographic changes in altered mental state.

PMID- 8882547
TI  - Clinics in diagnostic imaging (6).
AB  - A nine-month-old Chinese girl presented with a large buttock mass. Serum alpha
      fetoprotein level was elevated. Plain radiographs, computerised tomography and
      magnetic resonance imaging demonstrated a solid heterogeneous presacral mass. A
      sacrococcygeal teratoma was excised using the abdominoperineal approach. The
      patient responded well to multiagent chemotherapy. The features of this tumour
      are discussed, with emphasis on the role of imaging.

PMID- 8882548
TI  - Part II--controversies surrounding and following Rontgen's discovery.

PMID- 8882549
TI  - Scleroderma secondary to silica exposure--a case report.
AB  - In recent years there have been many reports of connective tissue diseases
      especially scleroderma following exposure to silica and silicone. We report a 51
      year-old Chinese who developed a scleroderma-like disease and pulmonary silicosis
      eight years after exposure to silica. To our knowledge, this is the first case to
      be reported in Malaysia.

PMID- 8882550
TI  - Stenting of stenosis of the abdominal aorta.
AB  - Isolated abdominal aortic stenosis resulting in bilateral lower limb claudication
      is uncommon in Asians. We report a 75-year-old Oriental man with isolated
      abdominal aortic stenosis who underwent intraluminal stenting, resulting in the
      abolishment of a 76 mmHg gradient. As the stenotic segment was local, only the
      mid-segment of the Palmaz stent was apposed to the aortic wall. Follow-up
      ultrasound scans showed that the partially apposed stent was potent, with no
      thrombosis in the free space between the stent and the wall. Hence, although
      aortic stenting in this patient resulted in partial apposition of the stent to
      the aortic wall, there was no thrombosis or migration of the stent. The patient
      remained symptom-free one year post-stenting. Stenting in this patient with
      failed balloon angioplasty was a safe and efficacious method of treating
      significant isolated abdominal aortic stenosis.

PMID- 8882551
TI  - Malignant melanoma of the oesophagus--a case report.
AB  - Primary malignant melanoma of the oesophagus is a rare presentation for melanoma
      and is also an unusual and aggressive form of oesophageal neoplasm. We present a
      57-year-old Chinese gentleman who underwent successful resection of a primary
      malignant melanoma of the oesophagus.

PMID- 8882552
TI  - Derealisation following head injury: a case report.
AB  - Depersonalisation and derealisation which are often present together, occur in a
      number of functional and organic conditions. However, their occurrence in the
      post-concussional syndrome has been previously described in only one case. A case
      is presented in which derealisation was the only presentation following a minor
      closed head injury. The possible aetiology is discussed.

PMID- 8882553
TI  - Biliary ascariasis and extrahepatic cholangiocarcinoma.

PMID- 8882554
TI  - Emergency department visits and hospitalizations for respiratory disease on the
      island of Hawaii, 1981 to 1991.
AB  - This study examined trends in and patterns of emergency department visits and
      hospitalizations for respiratory disease on the island of Hawaii from 1981 to
      1991. We found that emergency department visit rates and hospitalization rates
      for both asthma and COPD for 1987 to 1991 increased in all regions of the island
      in comparison with such rates for 1981 to 1986. Rates of emergency department
      visits and hospitalizations for chronic obstructive pulmonary disease or COPD,
      but not asthma, were significantly higher in the high-exposure Kona side of the
      island than in the intermittent-exposure Hilo side of the island during 1983 and
      1988 to 1990. We also found that during the weeks that winds were from the west,
      blowing volcanic air pollution toward Hilo, emergency department visits for
      asthma increased 15%. Some of the results of our study support the hypothesis
      that volcanic air pollution affects respiratory health on the island of Hawaii,
      while other results do not. Any future studies should include measurements of air
      pollutant levels.

PMID- 8882555
TI  - Early indicators of immunotoxicity: development of molecular biological test
      batteries.

PMID- 8882556
TI  - Development and validation of new screening tests for nephrotoxic effects.
AB  - Within the framework of an European Commission-funded project, groups of
      industrial workers exposed to heavy metals (cadmium, mercury and lead) or
      solvents were studied together with corresponding control groups. Eighty-one
      measurements were carried out on urine and serum samples and the scientific
      results together with individual questionnaire information were entered into a
      central database. Data obtained was assessed centrally and individually in
      subsidiary studies. The measurable contributions were assessed either singly or
      in combination, of smoking, gender, metal exposure and site, to nephrotoxicity.
      The potential value of each test as an indicator of nephrotoxicity was then
      assessed on the basis of sensitivity and specificity. A number of new tests
      including prostaglandins and for extracellular matrix components were
      investigated as well as established tests for renal damage and dysfunction. The
      data obtained from this comprehensive study emphasises the value of noninvasive
      biomarkers for the early detection of nephrotoxicity due to environmental toxins.
      The urinary profile varied with the type of environmental/occupational toxin. By
      careful selection of a small panel of markers they can be used to indicate the
      presence of renal damage, the principal region affected, and to monitor the
      progress of disease and damage. Biomarkers were also used to confirm and
      tentatively establish safe exposure levels to nephrotoxins.

PMID- 8882557
TI  - Biochemical markers of neurotoxicity. A review of mechanistic studies and
      applications.
AB  - Neurotoxicology presents major challenges to the development of biological
      markers in accordance to conventional research strategies. Because of the
      inaccessibility of the nervous system, one of the proposed alternatives is the
      study of biochemical signals in peripheral tissues which can easily and ethically
      be obtained in humans, and which could represent surrogate indicators of
      equivalent parameters in the nervous tissue. Considerable scientific support to
      this approach is provided by the results of recent investigations in major areas
      of pharmacology and psychobiology. Studies examining parameters of
      neurotransmission and second messenger systems in peripheral blood cells, and
      variations in the peripheral body fluid content of endogenous substances
      reflecting nervous tissue dysfunction or damage are presented in this paper as
      examples of efforts toward rational development and validation of novel
      indicators of nervous system toxicity. Cholinergic muscarinic receptors and
      calcium signalling in peripheral blood lymphocytes, myelin basic protein in
      cerebrospinal fluid, and blood polyamines are discussed as potential surrogate
      indicators based on the results of in vitro or in vivo animal studies of
      neurotoxic metals (mercury, triethyltin), pesticides (disulfoton), drugs of abuse
      (d-fenfluramine) and model epileptogenic compounds (kainic acid). Data from
      investigations examining serum prolactin, type B monoamine oxidase (MAO-B) and
      dopamine beta-hydroxylase (DBH) in workers occupationally exposed to manganese,
      lead or styrene are also presented. Although research in this field is still at
      its very early stage, current evidence suggests that (i) certain neurochemical
      markers may be valuably used in animal studies as a complement to conventional
      laboratory tests to augment their sensitivity or predictivity; (ii) a mechanistic
      research approach is required to establish which markers offer the greatest
      promise for application in human biomonitoring.

PMID- 8882558
TI  - A computer-based flowcharting system for clinical protocols.
AB  - In medicine, scientific and technological developments for investigation and
      treatment are proceeding at an ever increasing rate. Protocols for patient
      management are becoming ever more complicated. Rational design and scientific
      evaluation of protocols requires precise documentation. We propose a notation
      based on a series of simple flowcharts which describe procedures in increasing
      detail. Each step in a flowchart is justified by a reasoned argument, possibly
      including reference to published articles. General correctness requirements of a
      protocol include, for example, conformity with known indications and
      contraindications for investigations and treatments. These correctness
      requirements can be specified declaratively in mathematical logic and justified
      by reasoned argument. This makes the correspondence between a protocol and its
      scientific foundation even more explicit. Flowcharts of this nature are more
      easily created and modified using a personal computer. Furthermore, use of the
      computer enables a protocol to be checked automatically against its specification
      for more rapid identification of errors during development and maintenance of the
      protocol. We present the structured design of our flowcharting system in the 'Z'
      specification language, and we examine the practicality of our approach by means
      of a case study; the management of infertility. Our flowcharting system may also
      have application outside medicine where it is necessary to describe formal
      protocols for complex procedures.

PMID- 8882559
TI  - Two levelled design of an unified paediatric health care encounter.
AB  - The appearance of the new computer-based information technology has initiated the
      possibility of medical staff performing their everyday routine activities more
      effectively and efficiently. But to be able to use information technology as
      successfully as possible, unified and integrated medical encounters are urgently
      needed especially in the paediatrics field. The tendency to unify the medical
      encounter is relatively old and had already begun in the 'pre-computer era'.
      There were some, unpublished, attempts to unify the child's medical encounter
      during the last years in our country. Unfortunately they were all unsuccessful
      for various reasons, but it is our deep belief that the common factor for their
      lack of success was the inappropriateness of the methodology being used and the
      neglect of many system theory principles especially soft-system ones. It is the
      objective of this paper to briefly introduce MetaMet and its application in the
      design of the UNCLE (UNified Child's heaLth carE Encounter). MetaMet is an
      information system design approach, based on two-levelled design and its aim is
      to overcome at least some problems concerned with software crisis and to enable
      more successful design of (medical) information systems.

PMID- 8882560
TI  - Discovering objects in a blood recipient information system.
AB  - Application of object-oriented (OO) methodologies has been generally considered
      as a solution to the problem of improving the software development process and
      managing the so-called software crisis. Among them, object-oriented analysis
      (OOA) is the most essential and is a vital prerequisite for the successful use of
      other OO methodologies. Though there are already a good deal of OOA methods
      published, the most important aspect common to all these methods: discovering
      objects classes truly relevant to the given problem domain, has remained a
      subject to be intensively researched. In this paper, using the successful
      development of a blood recipient information system as an example, we present our
      approach which is based on the conceptual framework of responsibility-driven OOA.
      In the discussion, we also suggest that it may be inadequate to simply attribute
      the software crisis to the waterfall model of the software development life
      cycle. We are convinced that the real causes for the failure of some software and
      information systems should be sought in the methodologies used in some crucial
      phases of the software development process. Furthermore, a software system can
      also fail if object classes essential to the problem domain are not discovered,
      implemented and visualized, so that the real-world situation cannot be faithfully
      traced by it.

PMID- 8882561
TI  - Query-handling in MLM-based decision support systems.
AB  - Arden Syntax for Medical Logic Modules is a standard specification for creation
      and sharing of knowledge bases. The standard specification focuses on knowledge
      that can be represented as a set of independent Medical Logic Modules (MLMs) such
      as rules, formulas and protocols. The basic functions of an MLM are to retrieve
      patient data, manipulate the data, come to some decision, and possibly perform an
      action. All connections to the world outside an MLM are collected in the data
      slot of the MLM. The institution specific parts of these connections are inside
      the notation of curly brackets ([]) to facilitate sharing of MLM between
      institutions. This paper focuses on some of the problems that occur in relation
      to Arden Syntax and connections to a patient database such as database queries.
      Problems related to possibilities of moving one or several module(s) are also
      discussed, with emphasis on database connections. As an example, an MLM based
      Decision Support System (DSS) developed at Linkoping University is described.

PMID- 8882562
TI  - The design and development of hypertext courseware for CAL in diagnostic
      radiography.
AB  - Educational software has been designed and developed for training within the
      field of diagnostic radiography and is particularly concerned with the science
      and technology of diagnostic X-rays. The material has been structured into
      hypertext networks and as such allows interactive exploration of the available
      information. The courseware development platform was Microsoft Windows and
      authoring was accomplished using the constructional tool kit ToolBook. The
      resulting CAL package is highly graphical in nature with a user interface
      designed to meet the 'friendliness' demands of the end user group. Mechanisms for
      navigation through, and orientation within, the hypertext have also been
      established which support two levels of user activities. By changing the level of
      user freedom, students using the system as a learning tool are restricted to more
      structured routes than experienced staff using the courseware as an information
      resource. An aim of this work has been to provide interactive educational
      activities to support the main courseware, and consequently a novel application
      has been developed using dynamic data exchange (DDE) and the spreadsheet software
      Excel. Through a ToolBook front end students can interactively alter an X-ray
      spectrum by changing the operating conditions of a simulated X-ray tube.

PMID- 8882563
TI  - A learning tool in medical imaging: using procedure graphs in radiographic
      process simulation.
AB  - Teaching the procedural elements of imaging protocols and understanding the
      interrelationships and interdependencies of diagnostic X-ray system parameters
      and their effects on image quality, are among the main objectives of medical
      imaging training programs. A teaching tool is designed and implemented to support
      these goals. Tool design is influenced by hybrid learning system architectures
      and it is based on a graph approach, which is described. Implementation is
      carried out using a hypermedia development environment (Toolbook) coupled with a
      database (Paradox). The core of the system is an attributed priority graph,
      capable of supporting the organization of the domain knowledge, monitoring of
      user-machine interaction and managing the user-system dialogue. Use of this
      approach resulted in an interactive simulation tool, which provides computer
      aided learning support, to radiology related personnel, such as radiologists and
      radiographers. The potential value of the tool is not restricted only to didactic
      tasks, but may include trouble-shooting and documentation.

PMID- 8882564
TI  - Design and implementation of secure medical database systems.
AB  - Medical database security plays an important role in the overall security of
      medical information systems and networks. This is both because of the nature of
      this technology and its widespread use today. Database security not only involves
      fundamental ethical principles, but also essential prerequisites for effective
      medical care. The development of appropriate secure medical database design and
      implementation methodologies is an important research problem in the area and a
      necessary prerequisite for the successful development of such systems. The
      general framework and requirements for medical database security are given and a
      number of parameters of the secure medical database design and implementation
      problem are presented and discussed in this paper. A secure medical database
      development methodology is also presented which could help overcome some of the
      problems currently encountered.

PMID- 8882565
TI  - Perspectives of child neurology. Festschrift for Professor Yukio Fukuyama.
      Proceedings of the International Forum of Child Neurology. Tokyo, 9 July 1994.

PMID- 8882566
TI  - What is child neurology?

PMID- 8882567
TI  - Child neurology in Taiwan, ROC: past, present and future.
AB  - The status of child neurology in Taiwan is analysed as to three stages, i.e.,
      past, present and future. The year of demarcation between the past and present is
      set arbitrarily at 1988, when the academic organization changed. Each stage is
      reviewed from four aspects--academic organization of subspecialty training and
      research, change in disease pattern, diagnostic procedure, and treatment.

PMID- 8882568
TI  - Neonatal neurology, past present and future. A window on the brain.
AB  - Interest in the neurology of the newborn has been largely stimulated by the new
      advances of imaging; CT, cranial ultrasonography and MRI which for the first time
      allowed diagnosis of brain lesions in the live infant which in the past could
      only be made by post mortem examinations. (Ultrasound in particular, as it is
      safe, cheap and portable has been eminantly suitable for routine use in the
      nurseries to study the incidence, timing and evolution of the lesions in the
      neonatal period. While MRI is expensive and more difficult to perform it gives
      superb anatomical definition and is also safe for repeated examinations. It is
      thus very suitable to follow the evolution of the lesions into infancy). The aim
      of this presentation is to illustrate how an integrated approach with the
      combined use of imaging and clinical evaluations lead to a better understanding
      of antenatal and perinatal factors which may be responsible for the production of
      these lesions on one hand and the impact of these lesions on later development on
      the other.

PMID- 8882569
TI  - Advances in the genetics of hereditary hypertrophic neuropathy in childhood.
AB  - The peripheral neuropathies constitute approximately 30% of cases seen in a
      pediatric neuromuscular service. Two-thirds of such cases are chronic. Of the
      latter group roughly 70% are hereditary, 20% indeterminate and 10% acquired.
      There are definite chromosomal localizations for an increasing number of the
      hereditary neuropathies: to the region of the centromere of the X chromosome in
      an X-linked form of Charcot-Marie-Tooth (CMT) disease, to chromosome 17 in the
      commonest form of CMT, and to the long arm of chromosome 1, close to the Duffy
      locus, in a few kindreds with a rarer type of CMT. A duplication of DNA on the
      long arm of chromosome 17 is the commonest abnormality in autosomal dominant CMT.
      The duplicated region contains the gene for a 22 kDa myelin protein, PMP-22. The
      gene for PMP-22 is the site of a mutation in the hereditary neuropathy of the
      Trembler mouse. Some sporadic and inherited cases of chronic hypertrophic
      demyelinating neuropathy have recently been shown to be associated with specific
      mutations of the myelin protein P0 and PMP-22 loci. By contrast, a deletion
      encompassing the PMP-22 locus has been found in tomaculous neuropathy (hereditary
      liability to pressure palsies). Finally, mutations of the gap junction protein,
      connexin 32, have been shown to be responsible for X-linked dominant CMT.

PMID- 8882570
TI  - Deflazacort vs. prednisone in Duchenne muscular dystrophy: trends of an ongoing
      study.
AB  - Several studies have demonstrated the slowing effect of corticosteroids on the
      decline of muscle strength in Duchenne muscular dystrophy (DMD). Deflazacort
      (DFC) is supposed to have fewer side effects than prednisone (PRED). An ongoing
      double blind multicenter study is comparing the effects and side effects of
      deflazacort (0.9 mg/kg/day) and prednisone (0.75 mg/kg/day) in DMD. This interim
      report includes data for 67 boys between age 5 years and loss of ambulation.
      Besides the common clinical and laboratory data for chronic corticoid treatment,
      motor performance has been tested. Interim results, 3-15 months after starting
      the medication, show some scattering but no grouping of data for all the
      functions tested: timed motor functions, sum of the strength of 20 muscles
      according to a 10-point scale on manual testing, weight gain, osteocalcin and
      alkaline phosphatase. Only the changes in CK activity after 3 months medication
      might reflect two equal groups without any correlation with the initial activity
      or with other parameters. On average, there was no clear-cut loss of muscle
      strength or performance. Except for in 4 patients, who were excluded due to
      unacceptable weight gain and/or loss of ambulation, there were no side effects
      considered to be serious. The results suggest that (i) DFC and PRED in equal anti
      inflammatory dosage are similarly or equally efficient in slowing down the
      decline of muscle strength in DMD; (ii) benefits outweigh the side effects. This
      allows the study to continue as designed.

PMID- 8882571
TI  - Ethical problems in prenatal diagnosis: pediatric considerations.
AB  - In Europe, the recent advances in prenatal diagnosis and their practical
      consequences have elicited political rather than ethical discussions. An attempt
      will be made to outline and to ethically evaluate criteria pertaining to the
      termination of pregnancy because of malformation or disease of the fetus. Is it
      possible to determine the beginning of life, of an individual, of a personality?
      Are the severity of a malformation or disease, the duration of life to be
      expected, and the probable time of onset of relevant disease symptoms measurable
      parameters that can be used to arrive at an ethically correct or at least
      acceptable decision? In spite of efforts towards ethical objectivity, it appears
      difficult to set criteria completely independent of professional experience and
      responsibilities, and of legal liabilities sometimes resulting in dialectical
      patterns of thinking. The mothers' needs and wishes will play a paramount role in
      obstetric considerations. The paediatric point of view necessarily emphasizes the
      best interest of the child. Ethical criteria can not provide unequivocal answers.
      They can help, however, in a 'no-win' situation, to find an acceptable way
      between two 'evils': the death of an unborn child or the birth of a child with a
      severe disease.

PMID- 8882572
TI  - Correlations between clinical and neuropathological diagnosis of cortical
      anomalies in developmentally disabled children.
AB  - The capabilities and limitations of clinical diagnoses, particularly brain
      imaging of cortical anomalies, in developmentally disabled children are reviewed.
      Some aspects of diagnostic problems in generalized cortical dysgeneses, like
      lissencephaly type I and II, subcortical heterotopias, generalized
      polymicrogyria, or focal cortical anomalies and primary micrencephalies, are
      discussed.

PMID- 8882573
TI  - History of the tuberous sclerosis complex.
AB  - How the concept of the tuberous sclerosis complex (TSC) has developed over a
      period of time spanning 160 years has come form simple clinical observations,
      pathological studies and technological advances of imaging methods. It all began
      with PFO Rayer's color plate of a drawing of a patient who apparently had facial
      angiofibroma, published in the year 1835, and continued with von Recklinghausen's
      report of cardiac myomas and cerebral sclerosis in a newborn who had died minutes
      after birth. The seminal contribution was provided by D.M. Bourneville who, in
      1880, reported and named as tuberous sclerosis the neuropathological findings in
      a young patient with seizures, hemiplegia, and mental subnormality who also had
      renal tumors. We now know that TSC is a hamartomatosis, and thanks to studies of
      recent years using positional cloning and DNA analysis, we are beginning to
      understand the biological mechanisms of these disorders which include NF1, NF2
      and von Hippel-Lindau disease. Unique to TSC is that it is both phenotypically
      and genotypically heterogeneous. One of two suspected genes found in chromosome
      16 by positional cloning has been cloned (TSC2). Another one that was discovered
      earlier in chromosome 9 (TSC1) has not yet been characterized. The gene product
      from TSC2 has been named tuberin.

PMID- 8882574
TI  - Epilepsy etiology with special emphasis on immune dysfunction and neurovirology.
AB  - The etiology of epilepsy remains in most cases an enigma. Based on the finding of
      a genetically dependent immune dysfunction in focal epilepsies, brain specimens
      from 16 patients, ranging in age from 6 to 39 years and operated on for therapy
      resistant focal, mainly temporal lobe epilepsy were analyzed for the presence of
      viral DNA. The PCR technique was used for detection of viral DNA from the herpes
      virus group. HSV-1 was found in 44% CMV in 50%, and HHV-6 in 25%. Three patients
      were positive for more than one of these viruses. The control material,
      consisting of only 4 brain tissue samples, showed DNA from HSV-1 in one case.
      Until more brain samples from controls have been examined, caution must be taken
      before a viral etiology is applied to focal epilepsy.

PMID- 8882575
TI  - Ontogeny and topography of seizure regulation by the substantia nigra.
AB  - The substantia nigra pars reticulata (SNR) is a structure involved in the control
      of seizures, and its effects on seizures are age-dependent. GABAergic
      transmission in the SNR, mediated by GABAA receptors, influences seizure
      susceptibility. We have found that in the adult SNR there may be at least two
      segregated GABAA-sensitive SNR projection networks involved in regulating the SNR
      effects on seizures, perhaps reflecting the existence of an anticonvulsant and a
      proconvulsant network. The two networks with opposing effects on seizures
      originate from two topographically distinct regions. The anterior-medial region
      of the SNR is associated with anticonvulsant effects, whereas the posterior
      dorsal region of the SNR is associated with proconvulsant effects. To explain
      ontogenic differences in the SNR effects on seizures, we hypothesize that the two
      functionally segregated networks which influence the expression of seizures may
      become segregated with maturation. The increased seizure susceptibility of rat
      pups may be due, in part, to delayed development of this anterior-medial SNR
      anticonvulsant network.

PMID- 8882576
TI  - Molecular neurobiological approach to the pathogenesis of epilepsy: a preliminary
      study.
AB  - We studied the effects and the interactions of some candidate genes related to
      the pathogenesis of epilepsy using a domestic audiogenic epilepsy-prone rat,
      matched with the epilepsy-resistant Wistar rat, and primary fetal cerebral
      cortical neuronal cell cultures of both. The preliminary results showed that
      there was a possible abnormality of the CCK gene at the post-translational stage
      in the early postnatal period in P77PMC rat brain; the later rapidly increased
      rate of CCK-8 synthesis in the hippocampus and subcortical region may represent a
      compensatory response to the neuronal pathways involved in audiogenic seizures.
      CCK-8 can decrease the NMDA (1 microM)-induced free intracellular Ca2+
      concentration, so it seems to be an inhibitory neuromodulator. In neuronal cell
      cultures, the NMDA (0.1 microM)-induced c-fos mRNA expression on culture day 18
      in vitro was higher in P77PMC than Wistar rats (P < 0.05). Interleukin-1 (20 nM)
      can induce endogenous opioid mRNA expression and peptide release in neuronal cell
      cultures, which can be abolished by the addition of antisense oligos of c-fos/c
      jun to cell cultures treated with interleukin-1. Both interleukin-1 and opioids
      can increase the free intracellular Ca2+ concentration, and their specific
      antagonists can reverse their effects, so they both seem to be excitatory
      neuromodulators in the CNS.

PMID- 8882577
TI  - Reye syndrome: an international perspective.
AB  - An international perspective of Reye syndrome provides insights not noticeable
      with a parochial perspective. Sources of variation in Reye syndrome include
      geographic factors. The disappearance of Reye syndrome occurred globally, raising
      doubts about the importance of regional efforts to eliminate specific putative
      causes.

PMID- 8882578
TI  - Structure of the ternary complex of EF-Tu: macromolecular mimicry in translation.

PMID- 8882579
TI  - Reactive oxygen species and programmed cell death.
AB  - Bcl-2 is a proto-oncoprotein with apparently one function--to suppress programmed
      cell death (PCD)--yet how it does so remains a mystery. Several authors have
      proposed that Bcl-2 is an antioxidant that suppresses the formation or action of
      reactive oxygen species (ROS) and in this way inhibits PCD. However, three recent
      papers indicate that ROS are not required for PCD and that Bcl-2 can protect
      against cell death even under conditions where ROS are unlikely to be produced.

PMID- 8882580
TI  - The SANT domain: a putative DNA-binding domain in the SWI-SNF and ADA complexes,
      the transcriptional co-repressor N-CoR and TFIIIB.

PMID- 8882581
TI  - Chemical kinetic theory: understanding cell-cycle regulation.
AB  - Progress of a cell through its reproductive cycle of DNA synthesis and division
      is governed by a complex network of biochemical reactions controlling the
      activities of both M-phase- and S-phase-promoting factors. Standard chemical
      kinetic theory provides a disciplined method for expressing the molecular
      biologists' diagrams and intuition in precise mathematical form, so that
      qualitative and quantitative implications of our 'working models' can be derived
      and compared with experiment.

PMID- 8882582
TI  - Proteasomes: destruction as a programme.
AB  - Proteasomes are large multi-subunit protease complexes that selectively degrade
      intracellular proteins. Most of the proteins removed by these proteases are
      tagged for destruction by ubiquitination. Proteasomes have a role to play in
      controlling cellular processes, such as metabolism and the cell cycle, through
      signal-mediated proteolysis of key enzymes and regulatory proteins. They also
      operate in the stress response, by removing abnormal proteins, and in the immune
      response, by generating antigenic peptides.

PMID- 8882583
TI  - The role of MCM/P1 proteins in the licensing of DNA replication.
AB  - The DNA replication licensing system ensures that eukaryotic chromosomes
      replicate precisely once per cell cycle. A central component of the licensing
      system, RLF-M, has recently been shown to consist of a complex of Mcm/P1
      proteins. This result allows us to integrate data about the MCM/P1 family
      obtained in different eukaryotes, ranging from yeast to man, into a general
      picture of the way that chromosome replication is controlled.

PMID- 8882585
TI  - Is RNase-free really RNase for free?

PMID- 8882584
TI  - Processing the holliday junction in homologous recombination.
AB  - The Holliday junction is a well-known intermediate of homologous recombination.
      Recently, the proteins involved in the correct processing of the Holliday
      structure into mature recombinant molecules, namely RuvA, RuvB, RuvC and RecG
      have been isolated and characterized. This has culminated in a model for their
      synergistic mechanism of action and the solving of the RuvC crystal structure.

PMID- 8882586
TI  - Jean Brachet's alternative scheme for protein synthesis.

PMID- 8882587
TI  - Functional, endogenously expressed 5-hydroxytryptamine 5-ht7 receptors in human
      vascular smooth muscle cells.
AB  - Human uterine artery smooth muscle cells in culture were shown to express
      constitutively both 5-ht7 receptor mRNA and 5-ht7-like receptors functionally
      linked to cyclic AMP formation. 5-Carboxamidotryptamine (5-CT) and 5-HT enhanced
      forskolin-stimulated cyclic AMP accumulation in these cells, with pEC50 values of
      7.12 and 6.25, sumatriptan being very weakly active. Both methiothepin (0.1
      microM) and clozapine (1 microM), but not the 5-HT4-receptor antagonist, SDZ 205
      557 (10 microM) antagonized the effects of 5-CT. In reverse transcriptase
      polymerase chain reaction analysis, the mRNA for 5-ht7, but not for 5-HT4 or 5
      ht6 receptors was found to be strongly expressed in the same cells. These
      findings represent a further step toward the recognition of 5-ht7 receptors as
      real, functional receptors.

PMID- 8882588
TI  - Necessity of dual blockade of endothelin ETA and ETB receptor subtypes for
      antagonism of endothelin-1-induced contraction in human bronchi.
AB  - 1. Endothelin (ET)-1 has been postulated to be involved in the development of
      obstructive airway diseases in man. In the present study, we attempted to
      characterize ET receptor subtypes mediating ET-1-induced contraction in human
      isolated bronchi. The ET receptor antagonists used in the present study were BQ
      123 (ETA receptor-selective), BQ-788 (ETB receptor-selective) and BQ-928 (ETA/ETB
      dual). Sarafotoxin S6c (S6c) was also used as an ETB receptor-selective agonist.
      2. In human bronchi, ET-1 and S6c (10(-12)M to 10(-7) M) produced concentration
      dependent contraction with almost equal potency (pD2: 8.88 +/- 0.16 for ET-1 and
      9.42 +/- 0.15 for S6c). The contraction induced by S6c was competitively
      antagonized by BQ-788 alone (1 and 10 microM) with a pKB value of 7.49 +/- 0.21,
      suggesting that the stimulation of ETB receptors causes a contraction of human
      bronchi. However, contrary to expectation, the concentration-response curves for
      ET-1 were not affected by BQ-788. The ET-1- and S6c-induced contractions were not
      affected by BQ-123 (10 microM). Thus, ET-1-induced contraction of human bronchi
      is not antagonized by BQ-123 alone or by BQ-788 alone. 3. Combined treatment with
      10 microM BQ-123 and 10 microM BQ-788 significantly antagonized the contraction
      induced by ET-1 with a dose-ratio of 11. BQ-928 also significantly antagonized ET
      1-induced contraction with a pKB value of 6.32 +/- 0.24. 4. The specific binding
      of [125I]-ET-1 to human bronchial membrane preparations was inhibited by BQ-123
      (100 pM to 1 microM) by approximately 40%. Combination treatment with BQ-788 (100
      pM to 1 microM) completely inhibited the BQ-123-resistant component of [125I]-ET
      1 specific binding. 5. In conclusion, the present study demonstrates that BQ-788
      alone cannot inhibit ET-1-induced contractions in human bronchi, although human
      bronchial ETB receptors are BQ-788-sensitive. Furthermore, it was shown that
      blockade of both receptor subtypes antagonizes ET-1-induced contraction, and that
      both receptor subtypes co-exist in human bronchial smooth muscles. These findings
      suggest that ETA receptors as well as ETB receptors are involved in ET-1-induced
      contraction in human bronchi. If ET-1 is involved in human airway diseases, dual
      blockade of ETA and ETB receptors may be necessary to treat the diseases.

PMID- 8882589
TI  - Cardioprotective actions of oligotide, a single stranded polydeoxyribonucleotide
      complex, in myocardial ischaemia and reperfusion injury.
AB  - 1. The efficacy of oligotide, a single stranded polydeoxyribonucleotide complex,
      was examined in a feline model of myocardial ischaemia (MI: 90 min) and
      reperfusion (R: 270 min). Oligotide (15 mg kg-1 bolus) was administered
      intravenously 80 min after occlusion of the left anterior descending (LAD)
      coronary artery (i.e., 10 min prior to R) and continued for an additional 280 min
      (10 mg kg-1 h-1 infusion). 2. Oligotide-treated cats showed significantly smaller
      myocardial necroses and lower cardiac myeloperoxidase activities (significantly
      lower neutrophil infiltration) in the necrotic zone as compared to MI+R cats
      receiving only vehicle. 3. LAD coronary arteries isolated from MI+R cats
      exhibited a significant endothelial dysfunction (i.e., reduced endothelium
      dependent relaxation), and significantly increased adherence of polymorphonuclear
      neutrophils (PMNs) ex vivo. However, oligotide significantly preserved
      endothelial function and attenuated PMN adherence in ischaemic LAD coronary
      arteries. 4. Oligotide attenuated P-selectin expression on thrombin-stimulated
      platelets as well as PMN adherence to thrombin-stimulated coronary endothelium.
      Immunohistochemical examination in vivo revealed that oligotide treatment also
      significantly inhibited coronary endothelial P-selectin expression after 90 min
      MI and 20 min R. 5. Oligotide exerted a significant cardioprotection in MI+R
      injury. The mechanism appears to be related to attenuation of PMN-endothelial
      interaction and eventual infiltration into the ischaemic myocardium.

PMID- 8882590
TI  - Extent of salmeterol-mediated reassertion of relaxation in guinea-pig trachea
      pretreated with aliphatic side chain structural analogues.
AB  - 1. Salmeterol is a potent, selective and long acting beta 2-adrenoceptor agonist.
      In vitro, salmeterol exerts 'reassertion' relaxation of airways smooth muscle.
      Reassertion relaxation refers to the capacity of salmeterol to cause repeated
      functional antagonism of induced contraction when airway smooth muscle is
      intermittently exposed to, then washed free from, beta-adrenoceptor antagonists
      such as sotalol. The mechanism(s) underlying reassertion relaxation are unknown
      but may relate to high affinity binding of the long aliphatic side chain of
      salmeterol to an accessory site, distinct from the agonist recognition site, in
      or near the beta 2-adrenoceptor (exosite binding hypothesis). 2. In order to test
      the exosite hypothesis, three pure analogues of salmeterol, each exactly
      preserving the molecular structure of the aliphatic side chain but with zero or
      low efficacy at the beta 2-adrenoceptor were synthesized. The effect of pre
      incubating guinea-pig tracheal smooth muscle with these analogues on salmeterol
      induced reassertion relaxation was determined. 3. Computer Assisted Molecular
      Modelling of these molecules revealed that each of them exactly preserved the low
      energy linear conformation of the aliphatic side chain of salmeterol. Measurement
      of lipophilicity (octanol:water partition coefficient; log P) and direct
      partition into synthetic membranes (membrane partition coefficient; Kpmem) showed
      that all compounds had high affinity for lipids and membranes. In particular the
      biophysical properties of CGP 59162 (log P 1.89, Kpmem 16500) were very similar
      to salmeterol (log P 1.73, Kpmem 16800). 4. Two of the analogues, CGP 54103 and D
      2543 (1 microM), which are structural mimics of the side chain of salmeterol,
      differing slightly in their length, did not prevent either the initial relaxation
      induced by salmeterol (0.1 microM) or the reassertion relaxation; however, it was
      not possible to determine whether either of these molecules occupied the beta 2
      adrenoceptor. 5. The third analogue, CGP 59162, which has the substituents on the
      active saligenin head group of salmeterol in transposed positions, itself exerted
      a weak beta 2-adrenoceptor-mediated relaxation antagonized by ICI 118551 (beta 2
      selective antagonist) but not CGP 20712 (beta 1-selective antagonist) and, at
      higher concentrations CGP 59162 caused reassertion relaxation suggesting that it
      may occupy and activate the beta 2-adrenoceptor in a manner analogous to
      salmeterol. 6. CGP 59162, at concentrations up to ten fold molar excess, did not
      prevent or reduce salmeterol-induced reassertion relaxation. 7. In conclusion
      these data are not consistent with the existence of a distinct 'exosite'
      recognising the aliphatic side chain of salmeterol mediating reassertion.

PMID- 8882591
TI  - Pharmacological manipulation of cyclo-oxygenase-2 in the inflamed hydronephrotic
      kidney.
AB  - 1. Bradykinin (BK, 1 microgram) caused a small (2 fold at 6 h) increase in
      prostaglandin E2 (PGE2) in the normal rabbit kidney, perfused ex vivo. This was
      exaggerated (6 fold at 6 h) in the hydronephrotic kidney (HNK). The exaggerated
      release of PGE2 was attenuated by cycloheximide, an inhibitor of protein
      synthesis or by dexamethasone, a steroid known to inhibit the induction of cyclo
      oxygenase (COX-2). BK (1 microgram) when injected at 6 h of perfusion increased
      the release of PGE2 from 90 +/- 33 pg ml-1 min-1 to 3069 +/- 946 pg ml-1 min-1.
      This was reduced to 200 +/- 30 pg ml-1 min-1 in kidneys infused with
      cycloheximide (1 microM) and to 250 +/- 40 pg ml-1 min-1 in kidneys infused with
      dexamethasone (n = 8). 2. When tested on human and murine recombinant COX-1 and
      COX-2 enzymes, DuP-697 was at least 50 fold more selective for COX-2 than for COX
      1. 3. DuP-697 reduced the exaggerated release of PGE2 elicited by BK in the HNK
      (e.g., at 6 h of perfusion BK-evoked PGE2 release decreased from 3069 +/- 946 pg
      ml-1 min-1 to 187 +/- 22 pg ml-1 min-1 after perfusion with 1 microM DUP-697, n =
      8). 4. Cycloheximide, dexamethasone or DuP-697 at doses used to inhibit
      completely the exaggerated release of PGE2 in the hydronephrotic kidney, failed
      to inhibit the release of PGE2 elicited by the injection of BK (1 microgram) in
      the normal contralateral kidney. 5. Indomethacin (1 microM), a non-selective COX
      1 and COX-2 inhibitor, completely inhibited PGE2 release in the normal
      contralateral as well as in the hydronephrotic kidney. 6. We suggest that renal
      prostaglandin production in the normal kidney is driven by the activity of
      constitutive COX-1 while at sites of inflammation, such as the hydronephrotic
      kidney, there is induction of COX-2 that can be blocked selectively by anti
      inflammatory glucocorticoids or selective COX-2 inhibitors.

PMID- 8882592
TI  - Effect of dexfenfluramine on the transcriptional activation of CRF and its type 1
      receptor within the paraventricular nucleus of the rat hypothalamus.
AB  - 1. The present study investigated the effect of intraperitoneal (i.p.)
      administration of the indirect 5-hydroxytryptamine (5-HT) receptor agonist,
      dexfenfluramine, on the transcriptional activity of corticotropin-releasing
      factor (CRF) and its type 1 receptor in the brains of conscious male Sprague
      Dawley rats via in situ hybridization histochemistry (ISHH) using both intronic
      and exonic probe technology. 2. The immediate early gene (IEG) c-fos mRNA was
      also used as index of cellular activity, whereas localization between CRF
      immunoreactive (ir) perikarya and the IEG was accomplished to determine the site
      of CRF neuronal activation in the brain of dexfenfluramine-treated rats. 3.
      Thirty minutes, 1, 3, and 6 h after a single injection of either dexfenfluramine
      (10 mg kg-1) or the vehicle solution, adult male rats (230-260 g) were deeply
      anaesthetized and rapidly perfused with a 4% paraformaldehyde-borax solution
      (PF). The brains were removed from the skull, postfixed, and placed in a solution
      of 4% PF-10% sucrose overnight at 4 degrees C. Frozen brains were mounted on a
      microtome and cut from the olfactory bulb to the medulla in 30-microns coronal
      sections. 4. Dexfenfluramine induced a general neuronal activation as indicated
      by the strong signal of c-fos mRNA in several structures of the brain, including
      the parietal cortex, caudate putamen, circumventricular organs, medial preoptic
      area, bed nucleus of the stria terminalis, choroid plexus, choroidal fissure,
      supraoptic nucleus, paraventricular nucleus of the hypothalamus (PVN),
      paraventricular nucleus of the thalamus, central nucleus of the amygdala,
      dorsomedial nucleus of the hypothalamus, laterodorsal tegmental nucleus, locus
      coeruleus, and several subdivisions of the dorsal vagal complex. In most of these
      structures, the signal was maximal at 30 min, still strong and positive at 60
      min, largely decreased at 3 h, and had completely disappeared 6 h after
      injection. 5. In the parvocellular division of the PVN, the large majority of CRF
      ir perikarya displayed a positive signal for the mRNA encoding c-fos, indicating
      a profound CRFergic activation within this neuroendocrine nucleus after
      dexfenfluramine administration. 6. Colocalization between CRF-ir neurones and c
      fos positive cells was not detected in any other regions. This selective
      activation of PVN CRF neurones was also confirmed by the presence of CRF primary
      transcript; 30 min after i.p. injection of the indirect 5-HT agonist, a positive
      signal for CRF hnRNA was observed, specifically in the parvocellular PVN. 7.
      Transcription of the gene encoding the type 1 receptor for CRF was highly
      stimulated in the PVN following 5-HT activation. Although this hypothalamic
      nucleus exhibited a barely detectable signal under basal conditions,
      dexfenfluramine induced a strong signal of CRF1 receptor mRNA in the
      parvocellular PVN. Interestingly, CRF-ir neurones displayed a positive signal for
      the mRNA encoding the CRF1 receptor, 3 and 6 h after systemic treatment with
      dexfenfluramine. 8. These results indicate that although dexfenfluramine can
      generate a wide neuronal activation throughout the brain, this 5-HT agonist
      triggers the activity of CRF neurones selectively in the parvocellular division
      of the PVN, a mechanism possibly related to the activity of hypothalamic
      pituitary-adrenal axis. Induction of CRF1 receptor mRNA in CRF cells of the PVN
      indicates that neuroendocrine CRF neurones can be targeted by CNS CRF under 5-HT
      stimulation.

PMID- 8882593
TI  - Evidence for mediation by endothelium-derived hyperpolarizing factor of
      relaxation to bradykinin in the bovine isolated coronary artery independently of
      voltage-operated Ca2+ channels.
AB  - 1. The role of endothelium-derived hyperpolarizing factor and voltage-operated
      Ca2+ channels in mediating endothelium-dependent, NG-nitro-L-arginine (L-NOARG;
      100 microM) -resistant relaxations to bradykinin (BK), was examined in isolated
      rings of endothelium-intact bovine left anterior descending coronary artery. 2.
      Rings of artery were contracted isometrically to approximately 40% or their
      respective maximum contraction to 125 mM KCl Krebs solution (KPSSmax) with the
      thromboxane A2-mimetic, U46619. Relaxations to BK and the endothelium-independent
      NO donor, S-nitroso-N-acetylpenicillamine (SNAP), were normalized as percentages
      of reversal of the initial contraction to U46619. All experiments were carried
      out in the presence of indomethacin (3 microM). 3. BK caused concentration
      dependent relaxations [sensitivity (pEC50) 9.88 +/- 0.05; maximum relaxation
      (Rmax), 103.3 +/- 0.5%] in U46619-contracted rings of bovine coronary artery. L
      NOARG (100 microM) caused a significant (P < 0.01) 3 fold reduction in the
      sensitivity to BK (pEC50, 9.27 +/- 0.11) without affecting the Rmax (101.8 +/-
      2.3%). A similar, significant 3 fold reduction in sensitivity to BK with no
      change in Rmax was observed after treatment with oxyhaemoglobin (20 microM;
      pEC50, 9.18 +/- 0.13, P < 0.001) or a combination of oxyhaemoglobin (20 microM)
      and L-NOARG (100 microM; pEC50, 9.08 +/- 0.10, P < 0.001). Oxyhaemoglobin (20
      microM) either alone or in combination with L-NOARG (100 microM) caused an
      approximate 600 fold decrease in the sensitivity to SNAP. 4. The L-type voltage
      operated Ca2+ channel inhibitor, nifedipine (0.3 microM-3 microM), reduced the
      maximum contraction (Fmax) to isotonic 68 mM KCl Krebs solution (103.5 +/- 2.0%
      KPSSmax) by 85-90% (P < 0.001); yet, the highest concentration of nifedipine (3
      microM) caused only a small but significant reduction in both the sensitivity and
      Fmax to U46619. By contrast, nifedipine (3 microM) had no effect on the
      relaxation response to BK. Furthermore, a combination of nifedipine (3 microM)
      and L-NOARG (100 microM) had no further inhibitory effects on relaxations to BK
      (pEC50, 8.79 +/- 0.10; Rmax, 101.7 +/- 2.4%) than did L-NOARG (100 microM) alone
      (pEC50, 9.05 +/- 0.12; Rmax, 99.62 +/- 1.19). Also, nifedipine (0.3 microM and 3
      microM) had no effect on the maximum relaxation to the K+ channel opener,
      levcromakalim (0.3 microM). 5. In the presence of nifedipine (0.3 microM to
      control contractions induced by high KCl) and isotonic 68 mM KCl Krebs solution
      (to inhibit K+ channel activity), relaxations to BK (pEC50, 9.42 +/- 0.10; Rmax,
      93.9 +/- 1.8%) were similar to those observed in normal Krebs solution (pEC50,
      9.58 +/- 0.09; Rmax, 98.4 +/- 0.8%). However, in the presence of 68 mM KCl Krebs
      solution the inhibitory effect of L-NOARG (100 microM) on relaxations to BK
      (pEC50, 8.53 +/- 0.20; Rmax, 31.0 +/- 11.3%) was markedly greater than that in
      normal KCl Krebs solution (pEC50, 9.12 +/- 0.08; Rmax, 91.5 +/- 2.0%). Similar
      treatment with 68 mM KCl Krebs had no effect on relaxations to the NO donor,
      SNAP, yet abolished the response to the K+ channel opener, levcromakalim (0.3
      microM). 6. In summary, this study has shown that (1) NO synthesis in response to
      BK in bovine coronary artery endothelial cells in situ is likely to be abolished
      by L-NOARG, (2) NO-independent relaxations to BK are markedly attenuated by 68 mM
      KCl-containing Krebs, which, in the absence of L-NOARG, had no effect, (3)
      nifedipine blocked contractions to a maximum-depolarizing stimulus (KCl) yet had
      no effect on NO-independent relaxations to BK, and (4) maximum relaxations to
      levcromakalim were abolished by 68 mM KCl Krebs but were not affected by
      nifedipine. Therefore, we hypothesize that if smooth muscle hyperpolarization is
      involved in non-NO-, endothelium-dependent relaxation in bovine coronary arteries
      contracted with U46619, then it can accomplish this via a mechanism which does
      not i

PMID- 8882594
TI  - Vasorelaxant properties of norbormide, a selective vasoconstrictor agent for the
      rat microvasculature.
AB  - 1. The effects of norbormide on the contractility of endothelium-deprived rat,
      guinea-pig, mouse, and human artery rings, and of freshly isolated smooth muscle
      cells of rat caudal artery were investigated. In addition, the effect of
      norbormide on intracellular calcium levels of A7r5 cells was evaluated. 2. In
      resting rat mesenteric, renal, and caudal arteries, norbormide (0.5-50 microM)
      induced a concentration-dependent contractile effect. In rat caudal artery, the
      contraction was very slowly reversible on washing, completely abolished in the
      absence of extracellular calcium, and antagonized by high concentrations (10-800
      microM) of verapamil. The norbormide effect persisted upon removal of either
      extracellular Na+ or K+. The contractile effect of norbormide was observed also
      in single, freshly isolated smooth muscle cells from rat caudal artery. 3. In
      resting rat and guinea-pig aortae, guinea-pig mesenteric artery, mouse caudal
      artery, and human subcutaneous resistance arteries, norbormide did not induce
      contraction. When these vessels were contracted by 80 mM KCl, norbormide (10-100
      microM) caused relaxation. Norbormide inhibited the response to Ca2+ of rat aorta
      incubated in 80 mM KCl/Ca2(+)-free medium. Norbormide (up to 100 microM) was
      ineffective in phenylephrine-contracted guinea-pig and rat aorta. 4. In A7r5
      cells, a cell line from rat aorta, norbormide prevented high K(+)- but not 5
      hydroxytryptamine-induced intracellular calcium transients. 5. These findings
      indicate that in vitro, norbormide induces a myogenic contraction, selective for
      the rat small vessels, by promoting calcium entry in smooth muscle cells,
      presumably through calcium channels. In rat aorta and arteries from other
      mammals, norbormide behaves like a calcium channel entry blocker.

PMID- 8882595
TI  - The effect of ischaemia on endothelium-dependent vasodilatation and adrenoceptor
      mediated vasoconstriction in rat isolated hearts.
AB  - 1. The aim of this study was to investigate whether global ischaemia and
      reperfusion in rat isolated hearts affects endothelium-dependent vasodilatation
      and adrenoceptor-mediated vasoconstriction. In addition, it was first determined
      whether inhibition of the actions of nitric oxide (NO) influenced the responses
      to alpha-adrenoceptor agonists in the rat coronary vasculature. 2. In rat
      isolated, Langendorff perfused hearts, inhibition of NO with haemoglobin (Hb, 6
      microM) significantly inhibited the vasodilator responses to the endothelium
      dependent vasodilators, acetylcholine (ACh, 3-100 pmol), carbachol (CCh, 10-300
      pmol), bradykinin (Bk, 1-30 pmol) and histamine (0.3-10 nmol) but did not affect
      responses to the endothelium-independent vasodilator, sodium nitroprusside (SNP,
      0.01-1 nmol). 3. Inhibition of the action of NO by Hb significantly enhanced the
      vasoconstrictor response to the non-selective alpha-adrenoceptor agonist,
      noradrenaline (NA, 0.1-10 nmol) and the alpha 2-adrenoceptor agonist, B-HT 920
      (0.001-1 mumol) but had no effect on the vascular response to the alpha 1
      adrenoceptor agonist, methoxamine (MTX, 10-300 nmol). 4. In the perfused hearts
      ischaemia, induced by 30 min perfusion at 5% of the normal rate of flow, followed
      by 15 min of reperfusion (ischaemia/reperfusion) selectively impaired the
      vasodilator responses to ACh and CCh which act by muscarinic receptor stimulation
      but did not affect responses to the other endothelium-dependent vasodilators Bk
      and histamine or to the endothelium-independent dilator SNP. 5. After
      ischaemia/reperfusion the coronary vasoconstrictor responses to B-HT 920 were
      slightly but significantly enhanced whereas the responses to NA and MTX were
      unaffected. 6. Thus, in the rat isolated heart, low flow induced-ischaemia and
      reperfusion causes a selective impairment of muscarinic receptor-mediated
      vasodilatation but does not impair responses to all endothelium-dependent
      vasodilators. Enhanced constrictor responses to noradrenaline and B-HT 920 in the
      presence of Hb indicates that endogenous NO modulates the constriction of
      coronary resistance vessels in response to stimulation of alpha 2-adrenoceptors.
      Ischaemia and reperfusion in this isolated vascular bed caused only a small
      increase in the coronary vasoconstrictor response to alpha 2-adrenoceptor
      stimulation. It appears that in the rat isolated heart the degree of endothelial
      dysfunction caused by ischaemia/reperfusion is insufficient to cause a
      functionally significant change in alpha-adrenoceptor-mediated constriction.

PMID- 8882596
TI  - Functional effects of econazole on inducible nitric oxide synthase: production of
      a calmodulin-dependent enzyme.
AB  - 1. We performed experiments to examine the effects of an anti-fungal imidazole
      compound, econazole, on the regulation and effects of lipopolysaccharide
      inducible nitric oxide synthase (iNOS) activity in rat aortic rings and cultured
      J774 murine macrophage cells. 2. In endothelium-intact rings of thoracic aorta,
      phenylephrine caused a concentration-dependent contraction with EC50 of 1.9 +/-
      0.15 x 10(-8) M (n = 5). Following incubation with lipopolysaccharide (LPS, 5
      micrograms ml-1) for 8 h there was a right-shift in the concentration-response
      curve (EC50 3.1 +/- 0.28 x 10(-7) M, P < 0.05) with a depression in the maximum
      contraction from 1.44 +/- 0.25 g to 0.86 +/- 0.26 g (n = 4). Co-incubation of
      rings with econazole (1 x 10(-5) M) partially inhibited the LPS-induced loss of
      reactivity to phenylephrine (EC50 6.5 +/- 0.72 x 10(-8) M) and fully inhibited
      the reduction in maximum tension (1.49 +/- 0.19 g; n = 5). 3. In J774 cells,
      incubation with LPS (10 micrograms ml-1, 24 h) resulted in significant nitrite
      production that was inhibited by co-incubation with econazole (IC50 5.0 +/- 0.9 x
      10(-6) M; n = 5). In cells stimulated with LPS, production of L-[3H]-citrulline
      from L-[3H]-arginine was 6.41 +/- 0.22 pmol mg-1 protein min-1 (n = 3). This was
      inhibited by 92 +/- 6% by addition of NG-monomethyl-L-arginine (L-NMMA, 1 x 10(
      3) M; n = 3) to the homogenate but not by econazole (1 x 10(-5) M; n = 3). In
      contrast pretreatment of cells with econazole (1 x 10(-5) M) markedly reduced the
      LPS-induced [3H]-citrulline production (0.86 +/- 0.053 pmol mg-1 protein min-1; P
      < 0.01; n = 3). 4. In cells treated with LPS and econazole, L-[3H]-citrulline
      production was restored in a concentration-dependent manner by addition of
      calmodulin (1 x 10(-8)-3 x 10(-7) M) with an IC50 of 4.2 +/- 0.9 x 10(-8) M. 5.
      We have shown that econazole inhibits the functional and biochemical activity of
      iNOS in rat aortic rings and cultured J774 cells. Treatment of cells with
      econazole renders the NO synthase functionally inactive. In econazole-treated
      cells enzyme activity is restored by calmodulin suggesting that econazole may
      inhibit the binding of this essential co-factor to the enzyme following its
      production. These studies may have implications for the design of novel anti
      inflammatory agents working through the L-arginine-nitric oxide pathway.

PMID- 8882597
TI  - Differential action of NMDA antagonists on cholinergic neurotoxicity produced by
      N-methyl-D-aspartate and quinolinic acid.
AB  - 1. Injections of N-methyl-D-aspartate (NMDA) and quinolinic acid (Quin), agonists
      that activate NMDA receptors, into the rat nucleus basalis magnocellularis (nbM)
      produced a dose-related decrease in cholineacetyltransferase (ChAT) activity in
      the cerebral cortex and amygdala 7 days after injection. 2. In order to examine
      the possibility that NMDA and Quin activate different sub-types of NMDA receptors
      to produce central cholinergic neurotoxicity, the sensitivity of these agonists
      to the action of three different NMDA receptor antagonists, 2-amino-7
      phosphonoheptanoate (AP-7), 7-chlorokynurenate and dizolcipine (MK801) was
      examined by injecting a fixed dose of NMDA (60 nmol) or Quin (120 nmol) in
      combination with different doses of the antagonists into the nbM. 3. Both AP-7
      (0.6-15 nmol) and 7-chlorokynurenate (3.75-200 nmol), which block the NMDA
      receptor recognition site and glycine modulatory site respectively, produced a
      dose-related attenuation of the NMDA or Quin-induced decrease in ChAT activity in
      both the cortex and amygdala. Both antagonists showed a greater potency against
      the action of NMDA than against Quin. 4. MK801 (2-200 nmol), an NMDA receptor
      linked channel blocker, attenuated the Quin and NMDA response only at a high
      dose. Unlike AP-7 and 7-chlorokynurenate, MK801 did not exhibit a consistent
      difference in its potency as an antagonist against NMDA and Quin. 5. The
      differential antagonist actions of AP-7 or 7-chlorokynurenate against NMDA and
      Quin-induced cholinergic neurotoxicity suggest that the excitotoxic actions of
      these two agonists are mediated via distinct NMDA receptor sub-types. The NMDA-
      and Quin-sensitive receptors appear to differ with respect to properties of the
      receptor recognition and glycine modulatory sites that are associated with these
      receptors.

PMID- 8882598
TI  - Involvement of sensory neuropeptides in the development of plasma extravasation
      in rat dorsal skin following thermal injury.
AB  - 1. The involvement of the neuropeptides, substance P (SP) and calcitonin gene
      related peptide (CGRP) in plasma extravasation following thermal injury of rat
      dorsal skin was investigated. 2. Heat applied to the dorsal skin of anaesthetized
      rats by a temperature-controlled skin heater (1 cm diameter) for 5 min induced
      temperature-dependent plasma protein extravasation at 46 degrees C to 50 degrees
      C measured over the 20 min following initiation of heat. 3. The NK1-receptor
      antagonist, SR140333, at doses above 36 nmol kg-1, significantly (P < 0.05)
      inhibited plasma extravasation by up to 79 +/- 3% (120 nmol kg-1) after heat
      application at 48 degrees C and by up to 53 +/- 10% (120 nmol kg-1) after heat
      application at 50 degrees C. 4. The CGRP1-receptor antagonist, CGRP8-37, at doses
      of 200 and 400 nmol kg-1, significantly inhibited (P < 0.01) plasma extravasation
      by 55 +/- 9 and 60 +/- 12%, respectively, after heat application at 48 degrees C.
      At a dose of 200 nmol kg-1 CGRP8-37 inhibited plasma extravasation by 41 +/- 8%
      after heat application at 50 degrees C. 5. SR140333, 120 nmol kg-1, and CGRP8-37,
      200 nmol kg-1 together significantly (P < 0.01) inhibited plasma extravasation by
      84 +/- 15% after heating at 48 degrees C for 5 min. 6. In experiments where the
      response was measured for 0-5, 5-10, 10-15 or 15-20 min, SR140333, 120 nmol kg-1,
      significantly (P < 0.05) inhibited plasma extravasation which had accumulated
      during all the time periods measured. In comparison, CGRP8-37, 200 nmol kg-1, was
      significantly (P < 0.05) effective at time-points up to 15 min after initiation
      of injury. 7. In longer term experiments plasma protein extravasation continued
      for at least 95 min after initiation of thermal injury. SR140333, at a dose of
      120 nmol kg-1, significantly inhibited plasma extravasation for up to 65 min
      after initiation of injury. 8. In conclusion, the data from the present study
      demonstrate that both SP and CGRP are likely to have a role in the acute plasma
      extravasation after thermal injury. In addition, evidence suggests SP may have a
      role in plasma extravasation for up to 65 min.

PMID- 8882599
TI  - Regulation of the human histamine H1 receptor stably expressed in Chinese hamster
      ovary cells.
AB  - 1. The human H1 receptor gene expressed in Chinese hamster ovary cells (CHOhumH1)
      encodes a classical histamine H1 receptor with a pharmacology similar to that of
      the H1 receptor found in guinea-pig cerebellum and the endogenously expressed
      human H1 receptor in 1321N1 astrocytoma cells as determined by [3H]-mepyramine
      binding studies. 2. In CHOhumH1 cells, histamine induced a concentration
      dependent rise in inositol phosphates (EC50 2.23 +/- 0.97 microM) and a rapid
      increase of [Ca2+]i, followed by a sustained increase of [Ca2+]i upon addition of
      100 microM histamine. 3. Short-term exposure of CHOhumH1 cells to histamine (100
      microM) resulted in a decrease of subsequent histamine-induced Ca2+ responses.
      The histamine-induced desensitization appeared to be heterologous as the ATP
      induced Ca2+ response was also found to be affected. 4. The process of
      heterologous histamine-induced desensitization of the Ca2+ response in CHOhumH1
      cells can be ascribed to an alteration at the level of the intracellular Ca2+
      pool, as the Ca2+ response of caffeine (10 mM), which releases Ca2+ from
      intracellular Ca2+ stores was also attenuated upon short-term histamine exposure.
      5. In CHOhumH1 cells the PKC activator, PMA, was found to inhibit the histamine
      (100 microM)-induced Ca2+ response concentration-dependently (IC50 0.2 +/- 0.03
      microM) as well as the ATP (100 microM)-induced Ca2+ response. However, this
      inhibition was only partial and less effective than histamine-pretreatment.
      Moreover, in CHOhumH1 cells PKC downregulation induced by long-term exposure to
      PMA (1 microM) did not affect the histamine-induced desensitization nor did
      pretreatment with the specific PKC inhibitor Ro-31-8220 (10 microM), indicating
      that in CHOhumH1 cells PKC is probably not involved in the heterologous
      desensitization. 6. Long-term treatment of CHOhumH1 cells with histamine or other
      H1 agonists resulted in a time- and concentration-dependent decrease in the
      number of H1 receptor binding sites (maximal reduction: 47 +/- 5%). 7. Long-term
      exposure of CHOhumH1 cells to ATP or PMA did not affect H1 receptor density. 8.
      Both histamine (100 microM)- and ATP (100 microM)-induced Ca2+ responses were
      affected upon long-term exposure of cells to histamine (100 microM), which might
      be explained by an alteration at a level distant from the receptor. 9. These
      results show that in CHOhumH1 cells the human histamine H1 receptor is
      susceptible to short-term and long-term receptor regulation in which PKC does not
      seem to play a role. The CHOhumH1 cells therefore provide an excellent model
      system for studying the mechanism(s) of PKC-independent H1 receptor regulation.

PMID- 8882600
TI  - 5-HT2B receptor-mediated calcium release from ryanodine-sensitive intracellular
      stores in human pulmonary artery endothelial cells.
AB  - 1. We have characterized the 5-hydroxytryptamine (5-HT)-induced calcium
      signalling in endothelial cells from the human pulmonary artery. Using RT-PCR we
      show, that of all cloned G-protein coupled 5-HT receptors, these cells express
      only 5-HT1D beta, 5-HT2B and little 5-HT4 receptor mRNA. 2. In endothelial cells
      5-HT inhibits the formation of adenosine 3':5'-cyclic monophosphate (cyclic AMP)
      via 5-HT1D beta receptors but fails to activate phosphoinositide (PI) turnover.
      However, the latter pathway is strongly activated by histamine. 3. Despite the
      lack of detectable inositol phosphate (IP) formation in human pulmonary artery
      endothelial cells, 5-HT (pD2 = 5.82 +/- 0.06, n = 6) or the selective 5-HT2
      agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (pD2 = 5.66 +/-
      0.03, n = 7) elicited transient calcium signals comparable to those evoked by
      histamine (pD2 = 6.44 +/- 0.01, n = 7). Since 5-HT2A and 5-HT2C receptor mRNAs
      are not detectable in pulmonary artery endothelial cells, activation of 5-HT2B
      receptors is responsible for the transient calcium release. The calcium
      transients are independent of the inhibition of adenylate cyclase, since DOI does
      not stimulate 5-HT1D beta receptors. 4. Both, the 5-HT- and histamine-stimulated
      calcium signals were also observed when the cells were placed in calcium-free
      medium. This indicates that 5-HT triggers calcium release from intracellular
      stores. 5. Heparin is an inhibitor of the IP3-activated calcium release channels
      on the endoplasmic reticulum. Intracellular infusion of heparin through patch
      pipettes in voltage clamp experiments failed to block 5-HT-induced calcium
      signals, whereas it abolished the histamine response. This supports the
      conclusion that the 5-HT-induced calcium release is independent of IP3 formation.
      6. Unlike the histamine response, the 5-HT response was sensitive to micromolar
      concentrations of ryanodine and, to a lesser extent, ruthenium red. This implies
      that 5-HT2B receptors trigger calcium release from a ryanodine-sensitive calcium
      pool. 7. It has been postulated that cyclic ADP-ribose (cADPR) is a soluble
      second messenger which activates ryanodine receptors. However, calcium signals
      similar to the 5-HT response could not be elicited by intracellular infusion with
      cADPR. Furthermore, the subsequent application of 5-HT or DOI elicited a calcium
      signal that was not affected by the above pretreatment. 8. We conclude that human
      5-HT2B receptors stimulate calcium release from intracellular stores through a
      novel pathway, which involves activation of ryanodine receptors, and is
      independent of PI-hydrolysis and cADPR.

PMID- 8882601
TI  - Increase by adrenaline or angiotensin II of the accumulation of low density
      lipoprotein and fibrinogen by aortic walls in unrestrained conscious rats.
AB  - 1. Earlier experiments of ours with anaesthetized rabbits showed that infusions
      of catecholamines into the carotoid blood stream significantly increased the
      uptake of radioiodinated low density lipoprotein (LDL) by the artery wall after
      as little as 2 h. This observation has now been extended to much longer time
      periods, i.e., 6 days, and another species, viz. conscious and unrestrained rats;
      also to another pressor agent, angiotensin II, as well as to another plasma
      protein, fibrinogen. 2. Groups of rats were infused from subcutaneously implanted
      osmotic minipumps for 6 days. The infusions were either into a carotid artery or
      into the surrounding tissues, with essentially the same effects. Control animals
      were infused with saline, and test animals with either adrenaline or angiotensin
      II. The minipump concentration of adrenaline of 4-5 microM, which gave blood
      concentrations of 25-41 nM, increased the blood pressure significantly after 3
      days. The minipump concentration of angiotensin II of 9.9 mg ml-1 was chosen to
      produce similar increases in blood pressure. 3. Five days after starting the
      infusion, rats were injected i.v. with either homologous or human LDL labelled
      with [125I]-tyramine cellobiose (TC), or with [131I]-TC labelled human
      fibrinogen. Twenty-four hours later, the animals were killed and the
      radioactivities determined in the whole aorta. The labelled TC radioactivities
      represent primarily metabolised protein (because TC is trapped intracellularly),
      but also include the fraction of intact, i.e., non-metabolized protein in transit
      through the vessel wall. To determine the contribution of the latter, in some
      experiments we injected double-labelled [131I]-[125TC]-LDL only. These
      experiments showed that the [131I]-LDL counts representing protein in transit
      accounted for approx. 20% of the total 125TC counts, and that this percentage was
      not significantly affected by adrenaline or angiotensin II. Therefore, the bulk
      of the experiments was carried out with single labelled proteins, using 125I to
      label TC-LDL and 131I to label TC-fibrinogen. In these experiments, the
      radioactivity of the arterial wall thus provides a cumulative measure of the
      uptake and degradation of proteins. 4. Aortic wall radioactivities from rat and
      human LDL and from human fibrinogen were significantly increased by both agents.
      Adrenaline at 25-41 nM increased the radioactivities by 52 and 47% for rat and
      human LDL respectively, and by 31% for human fibrinogen; these differences were
      highly significant (P < 0.01). Angiotensin II at ca. 10 nM also increased the
      radioactivities significantly, by 21% for human LDL and by 109% for human
      fibrinogen (P < 0.05). 5. The results suggest that the accumulation of LDL and of
      fibrinogen by rat aorta is increased by adrenaline or by angiotensin II at
      concentrations which raise the blood pressure progressively and significantly
      after 3 or 5 days respectively.

PMID- 8882602
TI  - Thromboxane A2-mediated shape change: independent of Gq-phospholipase C--Ca2+
      pathway in rabbit platelets.
AB  - 1. Thromboxane A2 (TXA2) receptor-mediated signal transduction was investigated
      in washed rabbit platelets to clarify the mechanisms of induction of shape change
      and aggregation. 2. The TXA2 agonist, U46619 (1 nM to 10 microM) caused shape
      change and aggregation in a concentration-dependent manner. A forty-times higher
      concentration of U46619 was needed for aggregation (EC50 of 0.58 microM) than
      shape change (EC50 of 0.013 microM). The aggregation occurred only when external
      1 mM Ca2+ was present, but the shape change could occur in the absence of Ca2+.
      3. SQ29548 at 30 nM and GR32191B at 0.3 microM (TXA2 receptor antagonists)
      competitively inhibited U46619-induced shape change and aggregation with similar
      potency, showing that both aggregation and shape change induced by U46619 were
      TXA2 receptor-mediated events. However, ONO NT-126 at 1 nM, another TXA2 receptor
      antagonist, inhibited U46619-induced aggregation much more potently than the
      shape change, suggesting the possible existence of TXA2 receptor subtypes. 4. ONO
      NT-126 (2 nM to 3 microM) by itself caused a shape change without aggregation in
      a concentration-dependent manner, independent of external Ca2+. Therefore, ONO NT
      126 is a partial agonist at the TXA2 receptor in rabbit platelets. 5. U46619 (10
      nM to 10 microM) increased internal Ca2+ concentration ([Ca2+]i) and activated
      phosphoinositide (PI) hydrolysis in a concentration-dependent manner with a
      similar concentration-dependency. 6. U46619 (3 nM to 10 microM) also activated
      GTPase concentration-dependently in the membranes derived from platelets. U46619
      induced activation of GTPase was partly inhibited by treatment of membranes with
      QL, an antibody against Gq/11. 7. The EC50 values of U46619 in Ca2+ mobilization
      (0.15 microM), PI hydrolysis (0.20 microM) and increase in GTPase activity (0.12
      microM) were similar, but different from the EC50 value in shape change (0.013
      microM), suggesting that activation of TXA2 receptors might cause shape change
      via an unknown mechanism. 8. U46619-induced shape change was unaffected by W-7
      (30 microM), a calmodulin antagonist or ML-7 (30 microM), a myosin light-chain
      kinase inhibitor, indicating that an increase in [Ca2+]i might not be involved in
      the shape change. In fact, U46619 (10 nM) could cause shape change without
      affecting [Ca2+]i level, determined by simultaneous recordings. 9. [3H]-SQ29548
      and [3H]-U46619 bound to platelets at a single site with a Kd value of 14.88 nM
      and Bmax of 106.1 fmol/10(8) platelets and a Kd value of 129.8 nM and Bmax of
      170.4 fmol/10(8) platelets, respectively. The inhibitory constant Ki value for
      U46619 as an inhibitor of 3H-ligand binding was similar to the EC50 value of
      U46619 in GTPase activity, phosphoinositide hydrolysis and Ca2+ mobilization, but
      significantly different (P < 0.001 by Student's t test) from the effect on shape
      change. 10. Neither U46619 nor ONO NT-126 affected the adenosine 3',5'-cyclic
      monophosphate (cyclic AMP) level in the presence or absence of external Ca2+
      and/or isobutyl methylxanthine. 11. The results indicate that TXA2 receptor
      stimulation causes phospholipase C activation and increase in [Ca2+]i via a G
      protein of the Gq/11 family leading to aggregation in the presence of external
      Ca2+, and that shape change induced by TXA2 receptor stimulation might occur
      without involvement of the Gq-phospholipase C-Ca2+ pathway.

PMID- 8882603
TI  - The ontogenetic profiles of the pre- and postjunctional adenosine receptors in
      the rat vas deferens.
AB  - 1. The ontogenetic profiles of the prejunctional A1 and postjunctional A1 and A2
      receptors on the rat vas deferens were investigated, using a combination of
      functional and radioligand binding assays to follow the A1 receptors and
      functional assays alone to follow the development of the A2 receptors. 2. The
      prejunctional A1 receptor, assessed by the inhibitory action of N6
      cyclopentyladenosine (CPA) (3 nM-3 microM) on nerve-mediated contractions, was
      present from day 15 onwards, day 15 being the earliest age at which nerve
      mediated contractions could be detected. The potency of CPA was constant across
      the ages studied, with pD2 values ranging from 6.4-7.1, not significantly
      different from that previously observed in adult rat vas deferens. 3. The
      postjunctional A2 receptors, assessed by the inhibitory action of 5'-N
      ethylcarboxamidoadenosine (NECA) (10 nM-30 microM) on KCl-induced contractions
      were present from day 10 onwards, day 10 being the earliest age at which
      responses to KCl could be observed. The potency of NECA remained constant with an
      increase in age, with potency values, expressed as pEC25 values, ranging from 6.5
      7.0. 4. The postjunctional A1 receptor displayed a different development profile
      from that of the prejunctional A1 and postjunctional A2 receptors. Postjunctional
      A1 receptors were identified by the enhancement of KCl-induced contractions by
      CPA (10 nM-0.3 microM). At 10 and 15 days, CPA failed to enhance KCl-induced
      contractions. From day 20 to day 40, this enhancement increased with an increase
      in age and the level of enhancement achieved statistical significance from day
      30. 5. Radioligand binding studies using 1,3-[3H]-dipropyl-8-cyclopentylxanthine
      ([3H]-DPCPX) revealed binding sites characteristic of A1 receptors on the vas
      deferens from rats aged 20 days onwards. The density (Bmax) of A1 receptors
      expressed relative to protein content was greatest at day 20 (153 +/- 33 fmol mg
      1 protein) and declined at day 30 (43.9 +/- 3.7 fmol mg-1 protein) to a level
      commensurate with that previously determined in adult rat vas deferens (43.3 +/-
      12 fmol mg-1 protein). However, when expressed relative to tissue wet weight
      little variation in receptor density was observed between these ages (Bmax 0.13
      +/- 0.02 fmol mg-1 wet weight at 20 days; 0.17 +/- 0.01 fmol mg-1 wet weight at
      30 days). The binding affinity (KD) remained constant with an increase in age and
      was similar to the KD value previously generated for adult rat vas deferens
      (approximately 1 nM). At ages 10 and 15 days no reproducible binding could be
      detected. 6. These results show the differential development of the adenosine
      receptors on the rat vas deferens with postjunctional A1 receptors demonstrating
      delayed development, while prejunctional A1 and postjunctional A2 receptors were
      present from the earliest ages studied. In addition, comparison of binding
      studies and functional studies suggests that the binding studies detect only the
      A1 receptors present on the smooth muscle and not those present on the nerve
      terminals.

PMID- 8882604
TI  - Potentiation by 2,2'-pyridylisatogen tosylate of ATP-responses at a recombinant
      P2Y1 purinoceptor.
AB  - 1. 2,2'-Pyridylisatogen tosylate (PIT) has been reported to be an irreversible
      antagonist of responses to adenosine 5'-triphosphate (ATP) at metabotropic
      purinoceptors (of the P2Y family) in some smooth muscles. When a recombinant P2Y1
      purinoceptor (derived from chick brain) is expressed in Xenopus oocytes, ATP and
      2-methylthioATP (2-MeSATP) evoke calcium-activated chloride currents (ICl,Ca) in
      a concentration-dependent manner. The effects of PIT on these agonist responses
      were examined at this cloned P2Y purinoceptor. 2. PIT (0.1-100 microM) failed to
      stimulate P2Y1 purinoceptors directly but, over a narrow concentration range (0.1
      3 microM), caused a time-dependent potentiation (2-5 fold) of responses to ATP.
      The potentiation of ATP-responses by PIT was not caused by inhibition of oocyte
      ecto-ATPase. At high concentrations (3-100 microM), PIT irreversibly inhibited
      responses to ATP with a IC50 value of 13 +/- 9 microM (pKB = 4.88 +/- 0.22; n =
      3). PIT failed to potentiate inward currents evoked by 2-MeSATP and only
      inhibited the responses to this agonist in an irreversible manner. 3. Known P2
      purinoceptor antagonists were tested for their ability to potentiate ATP
      responses at the chick P2Y1 purinoceptor. Suramin (IC50 = 230 +/- 80 nM; n = 5)
      and Reactive blue-2 (IC50 = 580 +/- 130 nM; n = 6) reversibly inhibited but did
      not potentiate ATP-responses. Coomassie brilliant blue-G (0.1-3 microM)
      potentiated ATP-responses in three experiments, while higher concentrations (3
      100 microM) irreversibly inhibited ATP-responses. The results indicated that
      potentiation and receptor antagonism were dissociable and not a feature common to
      all known P2 purinoceptor antagonists. 4. In radioligand binding assays, PIT
      showed a low affinity (pKi < 5) for a range of membrane receptors, including:
      alpha 1, alpha 2-adrenoceptors, 5-HT1A, 5-HT1B, 5-HT2, 5-HT3, D1, D2, muscarinic,
      central benzodiazepine, H1, mu-opioid, dihydropyridine and batrachotoxin
      receptors. PIT showed some affinity (pKi = 5.3) for an adenosine (A1) receptor.
      5. In guinea-pig isolated taenia caeci, PIT (12.5-50 microM) irreversibly
      antagonized relaxations to ATP (3-1000 microM); PIT also directly relaxed the
      smooth muscle and histamine was used to restore tone. Relaxations to nicotine (10
      100 microM), evoked by stimulating intrinsic NANC nerves of taenia caeci
      preparations in the presence of hyoscine (0.3 microM) and guanethidine (17
      microM), were not affected by PIT (50 microM, for 25-60 min). 6. These
      experiments indicate that PIT causes an irreversible antagonism of ATP receptors
      but, for recombinant chick P2Y1 purinoceptors, this effect is preceded by
      potentiation of ATP agonism. The initial potentiation by PIT (and by Coomassie
      brilliant blue-G) of ATP-responses raises the possibility of designing a new
      class of modulatory drugs to enhance purinergic transmission at metabotropic
      purinoceptors.

PMID- 8882605
TI  - Characterization of a 5-HT1B receptor on CHO cells: functional responses in the
      absence of radioligand binding.
AB  - 1. Chinese hamster ovary (CHO) cells have been reported to be devoid of 5-HT
      receptors and have frequently been used as hosts for the expression of cloned 5
      HT receptors. Unexpectedly, 5-HT was found to induce profound inhibition of
      forskolin-stimulated cyclic AMP production in these cells and the aim of this
      study was to classify the 5-HT receptor involved. 2. In CHO(dhfr-) cells 5-HT was
      a potent agonist and caused 80-100% inhibition of forskolin stimulated cyclic AMP
      production. A study using several 5-HT1 receptor agonists revealed the following
      potencies (p[A50]): RU24969 (9.09 +/- 0.17) > 5-carboxamidotryptamine (8.86 +/-
      0.20) > 5-HT (8.07 +/- 0.05) > CP-93,129 (7.74 +/- 0.10) > sumatriptan (5.93 +/-
      0.04). All five agonists achieved a similar maximum effect. Irreversible receptor
      alkylation studies yielded a pKA estimate of 7.04 +/- 0.34 for 5-HT. 3. The 5
      HT1A/1B antagonist, (+/-)-cyanopindolol (4-100 nM), caused parallel rightward
      shifts of the 5-HT concentration-effect curve with no change in asymptote. Schild
      analysis yielded a pKB estimate of 8.69 +/- 0.09 (Schild slope 1.13 +/- 0.10).
      (+/-)-Cyanopindolol actually behaved as a partial agonist with an intrinsic
      activity of 0.2-0.5 and a p[A50] of 8.55. 4. 5-HT (0.01-10 microM) also elicited
      a concentration-dependent increase in intracellular [Ca2+] in CHO(dhfr-) cells
      thus demonstrating that dual coupling is not a phenomenon restricted to systems
      in which there is overexpression of transfected receptors. 5. This agonist and
      antagonist profile is consistent with the presence of a 5-HT1B receptor. 8-OH
      DPAT (1 microM) and renzapride (3 microM) were without effect on forskolin
      stimulated cyclic AMP production and ketanserin (0.3 microM) did not antagonize
      the inhibition produced by 5-HT, thus excluding the involvement of 5-HT1A, 5-HT4,
      and 5-HT2 receptors. 6. The possibility that expression of a 5-HT1B receptor was
      associated with the dhfr- mutation was excluded since RU24969, 5-HT and CP-93,129
      were also potent agonists in unmutated, CHO-K1 cells: p[A50] 9.03 +/- 0.03, 8.34
      +/- 0.05, 7.69 +/- 0.07 respectively, and (+/-)-cyanopindolol (0.1 microM)
      shifted the 5-HT curve to the right and yielded a pA2 estimate of 8.70 +/- 0.06.
      7. Little or no specific binding of [3H]-5-HT (0.1-200 nM) or of the high
      affinity ligand [125I]-iodocyanopindolol (0.01-3 nM) to CHO(dhfr-) cell membranes
      could be detected. 5-HT also failed to elicit any increase in the binding of
      [35S]-GTP gamma S to CHO membranes. 8. In conclusion, cultured CHO cells express
      5-HT1B receptors which are negatively coupled to adenylyl cyclase and positively
      coupled to increases in intracellular calcium. The absence of radioligand binding
      was unexpected in view of the high potency of 5-HT and the partial agonist
      activity of the normally 'silent' competitive antagonist, (+/-)-cyanopindolol.
      This implies very efficient receptor-effector coupling of a low density of 5-HT1B
      receptors. Clearly, the absence of detectable radioligand binding cannot be
      assumed to mean the absence of receptors capable of eliciting a significant
      functional response.

PMID- 8882606
TI  - Characterization of the pharmacological profile of the potent LTB4 antagonist CP
      105,696 on murine LTB4 receptors in vitro.
AB  - 1. Binding of [3H]-leukotriene B4 ([3H]-LTB4) to murine spleen membranes (MSM)
      was determined. 2. Scatchard analyses of [3H]-LTB4 binding indicated the presence
      of high (KD1 = 1.7 nM) and low (KD2 = 7.5 nM) affinity receptors on MSM with Bmax
      values of 151 fmol mg-1 protein (Bmax1) and 354 fmol mg-1 protein (Bmax2),
      respectively. 3. CP-105,696, a potent LTB4 antagonist, inhibited [3H]-LTB4 (0.67
      nM) binding to the high affinity receptor on MSM, IC50 = 30.2 nM, Ki = 17.7 nM
      with a Hill coefficient of 0.93. 4. Scatchard analyses of [3H]-LTB4 binding to
      MSM in the presence of CP-105,696 indicated that the high-affinity receptor was
      inhibited in a non-competitive manner and the low-affinity receptor in a
      competitive manner. 5. Isolated peripheral blood murine neutrophils (MN)
      responded chemotactically to LTB4, EC50 = 2.5 nM. CP-105,696 blocked this
      response, IC50 = 2.3 nM. When examined over a full concentration-response range
      of LTB4, CP-105,696 inhibited chemotaxis in a non-competitive manner. 6. Murine
      neutrophils in anticoagulated whole blood upregulated the integrin, complement
      receptor type 3 (CD11b/CD18, Mac-1) in response to LTB4, EC50 = 20 nM and this
      was inhibited by CP-105,696 in a competitive manner. 7. These results provide
      evidence that MSM have specific binding sites for LTB4, and as exemplified by CP
      105,696, that these receptors may be useful for determining the potency and
      nature of antagonism of novel LTB4 receptor antagonists.

PMID- 8882607
TI  - Desensitization of AMPA receptors and AMPA-NMDA receptor interaction: an in vivo
      cyclic GMP microdialysis study in rat cerebellum.
AB  - 1. Desensitization is an important characteristic of glutamate receptors of the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type. 2. Stimulation
      of N-methyl-D-aspartate (NMDA) or AMPA receptors in cerebellum results in
      increased production of cyclic GMP. We have investigated AMPA receptor
      desensitization in vivo by monitoring extracellular cyclic GMP during
      intracerebellar microdialysis in conscious unrestrained adult rats. 3. Local
      infusion of AMPA (10 to 100 microM) caused dose-related elevations of cyclic GMP
      levels. The effect of AMPA was prevented by the non-NMDA receptor antagonist, 6,7
      dinitroquinoxaline-2,3-dione (DNQX) and by the nitric oxide (NO) synthase
      inhibitor NG-nitro-L-arginine (L-NOARG). 4. In the absence of AMPA, DNQX lowered
      the basal levels of cyclic GMP whereas the NMDA receptor channel antagonist
      dizocilpine (MK-801) was ineffective. 5. Cyclothiazide, a blocker of AMPA
      receptor desensitization, potentiated the cyclic GMP response to exogenous AMPA.
      Moreover, cyclothiazide (100-300 microM) produced on its own dose-dependent
      elevations of extracellular cyclic GMP. The cyclothiazide-induced response was
      prevented not only by DNQX but also by MK-801. 6. While the cyclic GMP response
      elicited by AMPA was totally insensitive to MK-801, the response produced by AMPA
      (10 microM) plus cyclothiazide (30 microM) was strongly attenuated by the NMDA
      receptor antagonist (30 microM). 7. The results suggest that (a) AMPA receptors
      linked to the NO-cyclic GMP pathway in the cerebellum can undergo desensitization
      in vivo during exposure to exogenous AMPA; cyclothiazide inhibits such
      desensitization; (b) AMPA receptors (but not NMDA receptors) are 'tonically'
      activated and kept in a partly desensitized state by endogenous glutamate; (c) if
      cyclothiazide is present, activation of AMPA receptors may permit endogenous
      activation of NMDA receptors.

PMID- 8882608
TI  - Mediation of cimetidine secretion by P-glycoprotein and a novel H(+)-coupled
      mechanism in cultured renal epithelial monolayers of LLC-PK1 cells.
AB  - 1. Previous studies have shown that the weak base, cimetidine, is actively
      secreted by the renal proximal tubule. In this study we have examined the
      transport of cimetidine by renal LLC-PK1 epithelial cell monolayers. 2. In LLC
      PK1 cell monolayers the basal-to-apical flux of cimetidine was significantly
      greater than the apical-to basal flux, consistent with net secretion of
      cimetidine in a basal-to-apical direction. 3. Net secretion of cimetidine was
      significantly (70%) reduced by the addition of either 100 microM verapamil or 100
      microM nifedipine to the apical membrane. The reduction in net secretion was the
      result of an inhibition of basal-to-apical flux; these agents had no effect upon
      flux in the apical-to-basal direction. These results suggest that cimetidine
      secretion is mediated primarily by P-glycoprotein located in the apical membrane.
      In addition we found no evidence of a role for organic cation antiport in the
      secretion of cimetidine. 4. In the presence of an inwardly directed proton
      gradient across the apical membrane (pH 6.0), cimetidine secretion was
      significantly reduced compared to that measured at an apical pH of 7.4. The
      reduction in net secretion at pH 6.0 was the result of a stimulation of
      cimetidine uptake across the apical membrane. This pH-dependent uptake mechanism
      was sensitive to inhibition by DIDS (100 microM). 5. Experiments with BCECF
      (2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein) loaded monolayers
      demonstrated that cimetidine influx across the apical membrane was associated
      with proton flow into the cell and was sensitive to inhibition by DIDS. 6. These
      results suggest that net secretion of cimetidine across the apical membrane is a
      function of the relative magnitudes of cimetidine secretion mediated by P
      glycoprotein and cimetidine absorption mediated by a novel proton-coupled, DIDS
      sensitive transport mechanism.

PMID- 8882609
TI  - Acute inflammatory response in the mouse: exacerbation by immunoneutralization of
      lipocortin 1.
AB  - 1. An immuno-neutralization strategy was employed to investigate the role of
      endogenous lipocortin 1 (LC1) in acute inflammation in the mouse. 2. Mice were
      treated subcutaneously with phosphate-buffered solution (PBS), non-immune sheep
      serum (NSS) or with one of two sheep antisera raised against LC1 (LCS3), or its N
      terminal peptide (LCPS1), three times over a period of seven days. Twenty four
      hours after the last injection several parameters of acute inflammation were
      measured including zymosan-induced inflammation in 6-day-old air-pouches, zymosan
      activated serum (ZAS)-induced oedema in the skin, platelet-activating factor
      (PAF)-induced neutrophilia and interleukin-1 beta (IL-1 beta)-induced
      corticosterone (CCS) release. 3. At the 4 h time-point of the zymosan inflamed
      air-pouch model, treatment with LCS3 did not modify the number of
      polymorphonuclear leucocytes (PMN) recruited: 7.84 +/- 1.01 and 7.00 +/- 0.77 x
      10(6) PMN per mouse for NSS- and LCS3 group, n = 7. However, several other
      parameters of cell activation including myeloperoxidase (MPO) and elastase
      activities were increased (2.2 fold, P < 0.05, and 6.5 fold, P < 0.05,
      respectively) in the lavage fluids of these mice. Similarly, a significant
      increase in the amount of immunoreactive prostaglandin E2 (PGE2; 1.81 fold, P <
      0.05) and IL-1 alpha (2.75 fold, P < 0.05), but not tumour necrosis factor-alpha
      (TNF-alpha), was also observed in LCS3-treated mice. 4. The recruitment of PMN
      into the zymosan inflamed air-pouches by 24 h had declined substantially (4.13 +/
      0.61 x 10(6) PMN per mouse, n = 12) in the NSS-treated mice, whereas high values
      were still measured in those treated with LCS3 (9.35 +/- 1.20 x 10(6) PMN per
      mouse, n = 12, P < 0.05). A similar effect was also found following sub-chronic
      treatment of mice with LCPS1: 6.48 +/- 0.10 x 10(6) PMN per mouse, vs. 2.77 +/-
      1.20 and 2.64 +/- 0.49 x 10(6) PMN per mouse for PBS- and NSS-treated groups (n =
      7, P < 0.05). Most markers of inflammation were also increased in the lavage
      fluids of LCS3-treated mice: MPO and elastase showed a 2.47 fold and 17 fold
      increase, respectively (P < 0.05 in both cases); TNF-alpha showed a 11.1 fold
      increase (P < 0.05) whereas the IL-1 alpha levels were not significantly
      modified. PGE2 was still detectable in most (5 out of 7) of the mice treated with
      LCS3 but only in 2 out of 7 of the NSS-treated mice. 5. Intradermal injection of
      50% ZAS caused a significant increase in the 2 hoedema formation in the skin of
      LCS3-treated mice in comparison to PBS- and NSS-treated animals: 16.7 +/- 1.5
      microliters vs. 10.8 +/- 1.2 microliters and 10.2 +/- 1.0 microliters,
      respectively (n = 14 mice per group, P < 0.05). ZAS-induced oedema had subsided
      by 24 h in control animals but a residual significant amount of extravasation was
      still detectable in LCS3-treated mice: 4.4 +/- 0.8 microliters (P < 0.05). 6. A
      recently described model driven by endogenous glucocorticoids is the blood
      neutrophilia observed following administration of PAF. In our experimental
      conditions, a single bolus of PAF (100 ng, i.v.) provoked a marked neutrophilia
      at 2 h (2.43 and 2.01 fold) in NSS- and PBS-treated mice (n = 11), respectively,
      which was significantly attenuated in the animals treated with LCS3: 1.26 fold
      increase in circulating PMN (n = 11, P < 0.01 vs. NSS- and PBS-groups). 7.
      Intraperitoneal injection of IL-1 beta (5 micrograms kg-1) caused a marked
      increase in circulating plasma CCS by 2 h, to a similar extent in all
      experimental groups. In contrast, measurement of CCS levels in the plasma of mice
      bearing air-pouches inflamed with zymosan revealed significant differences
      between LCS3 and NSS-treated mice at the 4 h time-point: 198 +/- 26 ng ml-1 vs.
      110 +/- 31 ng ml-1 (n = 8, P < 0.05). 8. In conclusion, we found a remarkable
      exacerbation of the inflammatory process with respect to both humoral and
      cellular components in mice passively immunised agains

PMID- 8882610
TI  - Decreased susceptibility to copper-induced oxidation of rat-lipoproteins after
      fibrate treatment: influence of fatty acid composition.
AB  - 1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on
      plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to
      copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15
      day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB
      (39%). This effect was related to a significant reduction (67% for CFB and 56%
      for BFB) in the amount of circulating VLDL-protein. 3. Plasma total cholesterol
      was reduced by 28% and 45% in CFB- and BFB-treated animals, respectively, mainly
      by modification of the cholesteryl ester fraction. In contrast, GFB significantly
      increased total cholesterol (27%). No modification in the LDL protein or lipid
      content was introduced by fibrates, although GFB decreased the proportion of LDL
      triglycerides, at the expense of an increase in total cholesterol. 4. The fatty
      acid species carried by VLDL and LDL were affected after fibrate treatment. In
      general, both particles showed an increase in monounsaturated fatty acids (MUFA)
      (18:1) and a decrease in polyunsaturated fatty acids (PUFA) species (18:2 n-6,
      20:4 n-6, 18:3 n-3, 20:5 n-3). As a consequence, the ratio of PUFA/(SFA+MUFA) for
      the whole lipoproteins was markedly reduced. 5. The degree of copper-induced VLDL
      and LDL-oxidation was assessed by means of the analysis of lysine content,
      thiobarbituric acid reactive substances (TBARS) production and conjugated dienes
      formation. Lipoproteins obtained from fibrate-treated rats were more resistant to
      the oxidative challenge. For each lipoprotein, BFB was the most effective drug,
      followed by CFB and GFB. 6. The observed antioxidant effect can be ascribed to
      two independent phenomena produced by fibrates: the reduction of the amount of
      substrate for the oxidation process due to their hypolipidemic activity, and the
      alteration in the type of fatty acids transported by the lipoproteins towards an
      enrichment in species resistant to the oxidation process. 7. As similar
      lipoprotein fatty acid changes have been reported after fibrate treatment in
      human subjects, an antioxidant effect of fibrates in human therapy, independent
      of their well known hypolipidaemic activity, should be expected.

PMID- 8882611
TI  - Analysis of the signal transduction in the induction of nitric oxide synthase by
      lipoteichoic acid in macrophages.
AB  - 1. This study investigates the signal transduction mechanisms leading to the
      enhanced formation of nitric oxide (NO) due to the induction of NO synthase
      (iNOS) in murine J774.2 macrophages in culture activated with lipoteichoic acid
      (LTA), a cell wall component of the gram-positive bacterium Staphylococcus
      aureus. 2. LTA (10 microgram ml-1) caused within 24 h an enhanced accumulation of
      nitrite (an indicator of NO biosynthesis) in the supernatant of J774.2
      macrophages which was prevented by the non-selective NOS inhibitor NG-monomethyl
      L-arginine (L-NMMA; IC50: 35 microM) or by the iNOS-selective NOS inhibitor,
      aminoethyl-isothiourea (AE-ITU; IC50: 6 microM). The inhibition of nitrite
      formation afforded by these agents was prevented by excess L-arginine (3-30 mM),
      but not by D-arginine (3-30 mM). Furthermore, the degree of iNOS inhibition was
      similar when these NOS inhibitors were added to the macrophages 10 h after LTA.
      3. Pretreatment of J774.2 macrophages with cyclohexamide or dexamethasone
      prevented the enhanced formation of nitrite caused by LTA. This inhibition did
      not occur when dexamethasone or cyclohexamide were added to the cells 10 h after
      LTA. The increase in nitrite formation stimulated by LTA (10 micrograms ml-1) was
      not affected by polymyxin B (0.05-0.5 microgram ml-1), an agent which binds and
      inactivates endotoxin. 4. A specific inhibitor of phosphatidylcholine
      phospholipase C (PC-PLC), D609, prevented the increase in nitrite formation (IC50
      = 20 micrograms ml-1) caused by LTA. The inhibition afforded by D609 was
      significantly smaller when this agent was added to the cells 10 h after LTA. 5.
      The structurally distinct tyrosine kinase inhibitors, erbstatin, genistein, and
      tyrphostin AG126 prevented the formation of nitrite caused by LTA. The inhibition
      afforded by these compounds was significantly attenuated when they were added to
      the cells 10 h after LTA. In contrast, daidzein or tyrphostin A-1, which are
      inactive analogues of genistein and tyrphostin (up to a concentration of 10
      microM) did not affect the nitrite formation caused by LTA. 6. Inhibitors of the
      activation of the nuclear transcription factor NF-kappa B such as pyrrolidine
      dithiocarbamate (PDTC; an antioxidant and a metal chelator), butylated
      hydroxyanisole (BHA; an antioxidant), L-1-tosylamido-2-phenylethyl chloromethyl
      ketone (TPCK), calpain inhibitor I (both I kappa B-protease inhibitors), or
      rotenone (an antioxidant which inhibits electron transport) prevented the nitrite
      formation stimulated by LTA. The inhibition afforded by these agents was
      significantly smaller when they were added to the macrophages 10 h after LTA. 7.
      Incubation of J774.2 cells with LTA over 24 h resulted in the expression of iNOS
      protein (130 kDa) as identified by Western blot analysis. The expression of iNOS
      protein by LTA was significantly attenuated by cyclohexamide, D609, tyrphostin
      AG126, PDTC or by TPCK. 8. Thus, the signal transduction leading to the
      expression of iNOS protein and activity caused by LTA in murine J774.2
      macrophages involves (i) the activation of PC-PLC, (ii) phosphorylation of
      tyrosine kinase, and (iii) the activation of the transcription factor NF-kappa B.

PMID- 8882612
TI  - Evidence for human thromboxane receptor heterogeneity using a novel series of
      9,11-cyclic carbonate derivatives of prostaglandin F2 alpha.
AB  - 1. The pharmacological activity of a novel series of 9,11-cyclic carbonate
      derivatives of prostaglandin F2 alpha (PGF2 alpha) was investigated in various
      isolated smooth muscle preparations possessing different prostanoid receptor
      subtypes as well as in human platelets. Since subdivision of thromboxane (TP-)
      receptors into vascular/smooth muscle and platelet subtypes is a controversial
      subject, our studies included a human smooth muscle preparation (myometrium) in
      addition to the widely used rat aorta and human platelets as TP-receptor
      preparations. 2. Two members of that series, AGN191976 and AGN192093 were found
      to be highly potent and selective thromboxane-mimetics. AGN191976 and AGN192093
      contracted isolated tissues of the rat thoracic aorta with EC50 values of 0.32 +/
      0.08 and 1.30 +/- 0.53 nM, respectively. Both agonists were at least 10 times
      more potent than the benchmark TP-agonist, U-46619, in this preparation, whilst
      being at least 500 times less potent at other prostanoid receptors (DP, EP1, EP3,
      FP, IP) in vitro. 3. In human myometrial strips from pregnant and non-pregnant
      donors, both AGN191976 and AGN192093 were potent contractile agonists. The rank
      order of potency in myometrium of AGN191976 > AGN192093 > U-46619 correlated well
      with that in the rat aorta. In human platelet-rich plasma (PRP), however,
      AGN191976 had potent proaggregatory activity (EC50 = 16.3 +/- 1.4 nM), which is a
      TP-receptor-mediated event, whereas AGN192093 was a much weaker agonist (EC50 =
      37.9 +/- 2.0 microM). AGN192093 did not behave as an antagonist in the platelets,
      since it did not antagonize platelet aggregation induced by ADP, arachidonic
      acid, U-46619 or AGN191976. In human washed platelets, the activity profile of
      AGN191976 (EC50 = 4.15 +/- 0.52 nM) and AGN192093 (no aggregation up to 10
      microM) was similar to that obtained in PRP. 4. The involvement of TP-receptors
      was verified with the potent TP-antagonist, SQ29548. SQ29548 (0.1 microM in
      myometrium; 1 microM in aorta; 1 microM and 10 microM in platelets) antagonized
      responses to U-46619, AGN191976 and AGN192093 as expected. 5. In conclusion,
      AGN191976 and AGN192093, both 9,11-cyclic carbonate derivatives of PGF2 alpha,
      were found to be highly potent and selective thromboxane-mimetics in rat vascular
      and human myometrial smooth muscle. However, only AGN 191976 was a potent agonist
      at TP-receptors in human platelets. The differential activity of AGN192093 on TP
      receptor-mediated events in platelets and smooth muscle provides further evidence
      for a subdivision of TP-receptors. AGN192093 appears to be a useful tool for the
      pharmacological distinction of TP-receptor subtypes.

PMID- 8882613
TI  - Comparison of the chronic and acute effects of amiodarone on the calcium and
      potassium currents in rabbit isolated cardiac myocytes.
AB  - 1. The acute and chronic effects of amiodarone were studied on the transmembrane
      ionic currents in rabbit single ventricular myocytes at 35 degrees C by applying
      the whole-cell configuration of the patch-clamp technique. 2. Acute exposure to 1
      and 5 microM amiodarone significantly reduced the amplitude (-53.9 +/- 3.9%, n =
      5 and -64.0 +/- 2.0%, n = 3, P < 0.01), but chronic amiodarone treatment (i.p. 50
      mg kg-1 day-1 for 3-4 weeks) changed neither the amplitude nor the kinetics of
      the inward calcium current. 3. Both acute superfusion with amiodarone (1 and 5
      microM) and chronic amiodarone treatment significantly decreased the amplitude of
      the delayed rectifier outward potassium current (IK). 4. Acute application of
      amiodarone (1 and 5 microM) did not alter but chronic amiodarone treatment
      moderately depressed the transient outward current (Ito). 5. Neither the acute (1
      and 5 microM) nor the chronic amiodarone treatment changed the magnitude of the
      inward rectifier potassium current (Ik1). 6. It is concluded that acute
      amiodarone application and chronic amiodarone treatment alter transmembrane ionic
      currents of ventricular myocytes differently. This may explain, at least in part,
      the marked differences in the cardiac electrophysiological effects observed after
      acute and chronic amiodarone treatment in patients.

PMID- 8882614
TI  - Antagonistic actions of renal dopamine and 5-hydroxytryptamine: effects of amine
      precursors on the cell inward transfer and decarboxylation.
AB  - 1. The present work was designed to examine the interference of L-3,4
      dihydroxyphenylalanine (L-DOPA) on the cell inward transport of L-5
      hydroxytryptophan (L-5-HTP) and on its decarboxylation by aromatic L-amino acid
      decarboxylase (AAAD) in rat isolated renal tubules. 2. The accumulation of both L
      5-HTP and L-DOPA in renal tubules was found to occur through non-saturable and
      saturable mechanisms. The kinetics of the saturable component L-5-HTP and L-DOPA
      uptake in renal tubules were as follows: L-5-HTP, Vmax = 24.9 +/- 4.5 nmol mg-1
      protein h-1 and Km = 121 (95% confidence limits: 75, 193) microM (n = 5); L-DOPA,
      Vmax = 58.0 +/- 4.3 nmol mg-1 protein h-1 and Km = 135 (97, 188) microM (n = 5).
      When the saturation curve of L-5-HTP tubular uptake was performed in the presence
      of L-DOPA (250 microM), the maximal rate of accumulation of L-5-HTP in renal
      tubules was found to be markedly (P < 0.01) reduced (Vmax = 10.5 +/- 1.7 nmol mg
      1 protein h-1, n = 4); this was accompanied by a significant (P < 0.05) increase
      in Km values (325 [199, 531] microM, n = 4). 3. L-DOPA (50 to 2000 microM) was
      found to produce a concentration-dependent decrease (38% to 91% reduction) in the
      tubular uptake of 5-HTP; the Ki value (in microM) of L-DOPA for inhibition of L-5
      HTP uptake was found to be 29.1 (13.8, 61.5) (n = 6). 4. At the highest
      concentration tested the organic anion inhibitor, probenecid (10 microM) produced
      no significant (P = 0.09) changes in L-5-HTP and L-DOPA uptake (18% and 22%
      reduction, respectively). The organic cation inhibitor, cyanine 863 (1-ethyl-2
      [1,4-dimethyl-2-phenyl-6-pyrimidinylidene)methyl]-quino linium) produced a potent
      inhibitory effect on the tubular uptake of L-5-HTP (Ki = 212 [35, 1289] nM, n =
      8), being slightly less effective against L-DOPA uptake (Ki = 903 [584, 1396] nM,
      n = 5). The cyanine derivatives 1,1-diethyl-2,4-cyanine (decynium 24) and 1,1
      diethyl-2,2-cyanine (decynium 22) potently inhibited the tubular uptake of both L
      5-HTP (Ki = 100 [49, 204] and 120 [26, 561] nM, n = 4-6, respectively) and L-DOPA
      (Ki = 100 [40, 290] and 415 [157, 1094] nM, n = 5, respectively). 5. The Vmax and
      Km values for AAAD using L-DOPA as the substrate (Vmax = 479.9 +/- 74.0 nmol mg-1
      protein h-1; Km = 2380 [1630, 3476] microM; n = 4) were both found to be
      significantly (P < 0.01) higher than those observed when using L-5-HTP (Vmax =
      81.4 +/- 5.2 nmol mg-1 protein h-1, Km = 97 [87, 107] microM, n = 10). The
      addition of 5 mM L-DOPA to the incubation medium reduced by 30% (P < 0.02) the
      maximal rate of decarboxylation of L-5-HTP (Vmax = 56.7 +/- 3.1 nmol mg-1 protein
      h-1, n = 10) and resulted in a significant (P < 0.05) increase in Km values (249
      [228, 270] microM, n = 10). 6. The results presented suggest that L-5-HTP and L
      DOPA are using the same transporter (most probably, the organic cation
      transporter) in order to be taken up into renal tubular cells; L-DOPA exerts a
      competitive type of inhibition upon the tubular uptake and decarboxylation of L-5
      HTP. The decrease in the formation of 5-HT as induced by L-DOPA may also depend
      on a decrease in the rate of its decarboxylation by AAAD.

PMID- 8882615
TI  - Antagonistic actions of renal dopamine and 5-hydroxytryptamine: endogenous 5
      hydroxytryptamine, 5-HT1A receptors and antinatriuresis during high sodium
      intake.
AB  - 1. The present study has examined the effect of (+)-WAY 100135, a selective
      antagonist of 5-HT1A receptors, and ketanserin, an antagonist of 5-HT2 receptors,
      on the urinary excretion of Na+, K+, dopamine, 5-hydroxytryptamine (5-HT) and
      their metabolites in rats treated with the selective type A monoamine oxidase
      (MAO-A) inhibitor, Ro 41-1049 (15 mg kg-1 day-1) in conditions of normal sodium
      (NS) and high sodium (HS; 1.0% NaCl in drinking water) intake. 2. Male Wistar
      rats were placed in metabolic cages and were given tap water (NS diet) in the
      first 4 days of the study and then challenged to a HS diet for another 7 days. Ro
      41-1049 was given in drinking water only in the last 3 days of the HS diet,
      whereas (+)-WAY 100135 (5 and 10 mg kg-1 day-1, s.c.) or ketanserin (2 mg kg-1
      day-1, s.c.) were administered in the last 4 days of the HS intake period. 3.
      Daily urinary excretion (in nmol kg-1 day-1) of dopamine (82 +/- 2), 3,4
      dihydroxyphenylacetic acid (DOPAC; 198 +/- 9), homovanillic acid (HVA; 915 +/-
      47), 5-HT (586 +/- 37) and 5-hydroxyindoleacetic acid (5-HIAA; 1035 +/- 64) in
      the HS intake period was similar or higher than that in NS diet (dopamine = 68 +/
      2, DOPAC = 197 +/- 4, HVA = 923 +/- 42, 5-HT = 539 +/- 132, 5-HIAA = 1286 +/-
      95). The administration of Ro 41-1049 on 3 consecutive days reduced the urinary
      excretion of dopamine, DOPAC and HVA, respectively, by 35-51% (P < 0.05), 73-85%
      (P < 0.05) and 59-66% (P < 0.05); the urinary excretion of 5-HT increased 2 fold
      (P < 0.01) and the levels of 5-HIAA were reduced by 39-77% (P < 0.05). 4. During
      HS intake (7 days), daily urinary excretion of Na+ increased 5.5 fold (from 6.7
      +/- 0.2 to 36.5 +/- 0.9 mmol kg-1 day-1), without changes in the urinary
      excretion of K+ (from 11.2 +/- 0.2 to 11.9 +/- 0.5 mmol kg-1 day-1) and urinary
      osmolality (from 1083.8 +/- 26.7 to 1117.7 +/- 24.1 mOsm kg-1 H2O). MAO-A
      inhibition during HS intake was found to produce a 47-68% decrease in Na+
      excretion (from 39.1 +/- 0.7 to 15.1 +/- 2.5 mmol kg-1 day-1, n = 4; P < 0.02)
      and urine volume (from 160.4 +/- 3.3 to 43.8 +/- 9.0 ml kg-1 day-1, n = 4; P <
      0.02) without changes in K+ (from 11.1 +/- 0.5 to 9.2 +/- 0.6 mmol kg-1 day-1, n
      = 4) and creatinine (from 29.1 +/- 2.3 to 28.4 +/- 2.1 mg kg-1 day-1) excretion;
      urine osmolality increased 2 fold (from 936.3 +/- 40.3 to 2210.7 +/- 157.4 mOsm
      kg-1 H2O, n = 4; P < 0.02). Administration of (+)-WAY 100135 (5 and 10 mg kg-1
      day-1), but not of ketanserin (2 mg kg-1 day-1), was found to inhibit the
      antinatriuretic effect induced by Ro 41-1049 during HS intake. 5. It is suggested
      that MAO-A inhibition during HS intake leads to an increased availability of 5-HT
      in renal tissues, the effect of which is a decrease in the urinary excretion of
      Na+, involving the activation of tubular 5-HT1A receptors.

PMID- 8882616
TI  - Antagonistic actions of renal dopamine and 5-hydroxytryptamine: increase in Na+,
      K(+)-ATPase activity in renal proximal tubules via activation of 5-HT1A
      receptors.
AB  - 1. 5-Hydroxytryptamine (5-HT) is antinatriuretic. Since this effect of 5-HT is
      not accomplished by changes in glomerular haemodynamics, we have examined in this
      study whether 5-HT may influence sodium excretion by affecting the Na+, K(+)
      ATPase activity in renal cortical tubules. 2. Na+, K(+)-ATPase activity was
      determined as the rate of [32P]-ATP hydrolysis in renal cortical tubules in
      suspension. Basal Na+, K(+)-ATPase activity in renal tubules was 4.8 +/- 0.4
      mumol Pi mg-1 protein h-1 (n = 8). The 5-HT1A receptor agonist, (+/-)-8-hydroxy-2
      (di-n-propylamino) tetraline (8-OH-DPAT) (10 to 3000 nM) induced a concentration
      dependent increase (P < 0.05) in Na+, K(+)-ATPase activity with an EC50 value of
      355 nM (95% confidence limits: 178, 708). Maximal stimulation elicited by 3000 nM
      of 8-OH-DPAT was antagonized by the selective 5-HT1A receptor antagonist, (+)-WAY
      100135 10 to 1000 nM) with an IC50 value of 20 nM (14, 29); 0.3 microM (+)-WAY
      100135 completely abolished (P < 0.01) the stimulatory effect of 8-OH-DPAT. The
      stimulatory effect of 8-OH-DPAT was found to be time-dependent (15 +/- 2% and 66
      +/- 7% increase at 2.5 and 5.0 min, respectively). The 5-HT2 receptor agonist
      alpha-methyl-5-HT (100 to 3000 nM) did not induce any significant changes in Na+,
      K(+)-ATPase activity (5.0 +/- 1.5 mumol Pi mg-1 protein h-1; n = 4). 3. The
      stimulatory effect 8-OH-DPAT was absent when homogenates were used. Stimulation
      occurred at a Vmax concentration (70 mM) of sodium supporting the notion that
      stimulation occurs independently of increasing sodium permeability. 4. The
      inhibitory effect of dopamine (P < 0.05) on Na+, K(+)-ATPase activity was blunted
      by co-incubation with 8-OH-DPAT (0.5 microM). 5. It is concluded that activation
      of 5-HT1A receptors increases Na+, K(+)-ATPase activity in renal cortical
      tubules; this effect may represent an important cellular mechanism, at the tubule
      level, responsible for the antinatriuretic effect of 5-HT.

PMID- 8882617
TI  - Nitric oxide-mediated relaxation without concomitant changes in cyclic GMP
      content of rat proximal colon.
AB  - 1. We studied the relation of nitric oxide-mediated relaxation of longitudinal
      muscle to changes in cyclic GMP content of the tissue in the proximal colon of
      rats. 2. Dimethylphenylpiperazinium (DMPP) and electrical field stimulation (EFS)
      induced nitric oxide-mediated relaxation of the segments with a concomitant
      increase in cyclic GMP content. 3. LY 83583 and methylene blue, soluble guanylyl
      cyclase inhibitors, significantly inhibited the stimulatory effects of DMPP and
      EFS on the cyclic GMP content, but did not affect the relaxant responses of the
      segments to DMPP and EFS. 4. Rp-8 bromo cyclic GMPS, an inhibitor of cyclic GMP
      dependent protein kinase had no effect on DMPP- and EFS-induced relaxation. 5.
      These data strongly suggested that nitric oxide-mediated relaxation of the rat
      proximal colon is not associated with change in cyclic GMP content of the tissue.

PMID- 8882618
TI  - Interactions of 2,3-benzodiazepines and cyclothiazide at AMPA receptors: patch
      clamp recordings in cultured neurones and area CA1 in hippocampal slices.
AB  - 1. The 2,3-benzodiazepines GYKI 52466, GYKI 53405 and GYKI 53655 antagonized AMPA
      induced currents in cultured superior colliculus neurones in a non use-dependent
      manner (steady state IC50s: GYKI 52466 9.8 +/- 0.6 microM; GYKI 53405 3.1 +/- 0.6
      microM; GYKI 53655 0.8 +/- 0.1 microM). 2. Higher concentrations of all three
      antagonists slowed the onset kinetics and quickened the offset kinetics of AMPA
      induced currents indicative of an allosteric interaction with the AMPA
      recognition site. 3. Cyclothiazide (3-300 microM) dramatically slowed
      desensitization of AMPA-induced currents and potentiated steady state currents
      (EC50 10.0 +/- 2.5 microM) to a much greater degree than peak currents. Both tau
      on and tau off were also increased by cyclothiazide in a concentration-dependent
      manner (EC50: tau on 42.1 +/- 4.5 microM; tau off 31.6 +/- 6.6 microM). 4.
      Cyclothiazide (10-100 microM) shifted the concentration-response curves of the
      2,3-benzodiazepines to the right. For example, with 10 microM cyclothiazide the
      IC50s of GYKI 52466 and GYKI 53405 on steady-state AMPA-induced currents were
      57.9 +/- 9.5 and 41.6 +/- 1.5 microM, respectively. 5. GYKI 53405 and GYKI 52466
      concentration-dependently reversed the effects of cyclothiazide (100 microM) on
      offset kinetics (GYKI 53405 IC50 16.6 +/- 4.2 microM). However, the 2,3
      benzodiazepines were unable to reintroduce desensitization in the presence of
      cyclothiazide and even concentration-dependently slowed the onset kinetics of
      AMPA responses further (GYKI 53405 EC50 8.0 +/- 2.8 microM). 6. GYKI 52466
      decreased the peak amplitude of hippocampal area CA1 AMPA receptor-mediated
      excitatory postsynaptic currents (e.p.s.cs) (IC50 10.8 +/- 0.8 microM) with no
      apparent effect on response kinetics. Cyclothiazide prolonged the decay time
      constant of AMPA receptor-mediated e.p.s.cs (EC50 35.7 +/- 6.5 microM) with less
      pronounced effects in slowing e.p.s.c. onset kinetics and increasing e.p.s.c.
      amplitude. 7. Cyclothiazide (330 microM) shifted the concentration-response curve
      for the effects of GYKI 52466 on AMPA receptor-mediated e.p.s.c. peak amplitude
      to the right (GYKI 52466 IC50 26.9 +/- 9.4 microM). Likewise, GYKI 52466 (30-100
      microM)) shifted the concentration-response curve for the effects of
      cyclothiazide on AMPA receptor-mediated e.p.s.c. decay time constants to the
      right. 8. In conclusion, cyclothiazide and the 2,3-benzodiazepines seem to bind
      to different sites on AMPA receptors but exert strong allosteric interactions
      with one another and with other domains such as the agonist recognition site. The
      interactions of GYKI 52466 and cyclothiazide on AMPA receptor-mediated e.p.s.cs
      in area CA1 of hippocampal slices provide evidence that the decay time constant
      of these synaptic events are not governed by desensitization.

PMID- 8882619
TI  - Time course of changes in ETB receptor density and function in tracheal airway
      smooth muscle during respiratory tract viral infection in mice.
AB  - 1. In the current study, the density and function of ETA and ETB receptors in
      mouse tracheal airway smooth muscle were determined over the time course of
      respiratory tract infection with influenza A/PR-8/34 virus. 2. Quantitative
      autoradiographic studies using [125I]-endothelin-1 revealed that the tracheal
      airway smooth muscle from control mice contained ETA and ETB sites in the ratio
      of 49%:51% (+/- 2%, n = 29 mice). Respiratory tract viral infection was
      associated with increases in the density of ETA sites and decreases in the
      density of ETB sites at days 1, 2 and 4 post-inoculation which were reversible by
      day 19. For example, at day 4 post-inoculation, a time when the manifestations of
      viral infection were at or near their peak, the ratio of ETA:ETB sites was
      72%:28% (+/- 4%, n = 6 mice, P < 0.05). In contrast, at day 19 post-inoculation,
      by which time viral infection had essentially resolved, the ratio of ETA:ETB
      sites was similar to control (51%:49% (+/- 3%), n = 6 mice). 3. Endothelin-1 was
      a potent spasmogen in isolated tracheal airway smooth muscle preparations from
      control mice (ED70 = concentration producing 70% of contraction induced by 10
      microM carbachol = 6.3 nM (95% confidence limits, 4.0-10; n = 6 mice)). Neither
      the ETA receptor-selective antagonist, BQ-123 (3 microM), nor the ETB receptor
      selective antagonist, BQ-788 (1 microM) alone had any significant inhibitory
      effect on endothelin-1-induced contractions of mouse isolated tracheal smooth
      muscle. However, simultaneous treatment with BQ-123 (3 microM) and BQ-788 (1
      microM) resulted in a 10 fold rightward shift in the concentration-effect curve
      to endothelin-1 (ED70 = 60 nM, (44-90; n = 6 mice, P < 0.05)), indicating that
      contraction was mediated via both ETA and ETB receptors. 4. Endothelin-1 evoked
      similar concentration-dependent contractions of tracheal smooth muscle isolated
      from control and virus-inoculated mice. In the presence of the ETB receptor
      selective-antagonist, BQ-788 (1 microM), the potency and maximum response to
      endothelin-1 were similar in preparations from control and virus-inoculated mice
      at all time points investigated. However, unlike control responses, endothelin-1
      induced contractions in preparations from virus-infected mice were significantly
      inhibited by the ETA receptor-selective antagonist, BQ-123. For example, at day 4
      post-inoculation, the contractile response to 30 nM endothelin-1, in the presence
      of BQ-123 (3 microM), was only 20 +/- 12% (n = 6 mice, P < 0.05) of that produced
      in control preparations under similar conditions. However, at day 19 post
      inoculation, contraction evoked by 30 nM endothelin-1 in the presence of BQ-123
      (3 microM), was similar to that in preparations from control mice. 5. In summary,
      during the early stages (days 1-8 post-inoculation) of respiratory tract
      infection with influenza A/PR-8/34 virus, we observed decreases in the density of
      tracheal airway smooth muscle ETB receptors which were reflected in decreases in
      ETB receptor-mediated airway smooth muscle contraction. In addition, during the
      same period of viral infection we observed increases in the density of tracheal
      airway smooth muscle ETA receptors which were not associated with increased
      function of the ETA receptor-effector system linked to contraction. Virus
      associated modulation of ETA and ETB receptor density and function was reversible
      with recovery from infection.

PMID- 8882620
TI  - Allosteric modulation of an expressed homo-oligomeric GABA-gated chloride channel
      of Drosophila melanogaster.
AB  - 1. Functional GABA-gated chloride channels are formed when cRNA encoding the
      Drosophila melanogaster GABA receptor subunit RDL is injected into the cytoplasm
      of Xenopus oocytes. Two-electrode voltage-clamp was used to investigate
      allosteric modulation of GABA-induced currents recorded from the expressed,
      bicuculline-insensitive, RDL homo-oligomers. 2. Flunitrazepam (0.1 microM to 100
      microM) had no effect on the amplitude of responses to 10 microM GABA
      (approximately EC10), whereas 4'chlorodiazepam (100 microM) enhanced the
      amplitude of submaximal responses to GABA. 3-Hydroxymethyl-beta-carboline (1
      microM) and ethyl-beta-carboline-3-carboxylate (both 1 and 100 microM) had no
      effect on currents induced by 30 microM (approximately EC50) GABA. However 100
      microM 3-hydroxymethyl-beta-carboline reduced potentiation by 4'chlorodiazepam.
      3. The sodium salts of pentobarbitone (10 microM to 1 mM) and phenobarbitone (50
      microM to 1 mM) dose-dependently enhanced submaximal GABA responses. Neither
      barbiturate activated currents in the absence of GABA. 4. At 10 microM, the
      steroids 5 alpha-pregnan-3 alpha-ol-20-one and alphaxalone (5 alpha-pregnan-3
      alpha-ol-11,20-dione), potentiated submaximal GABA responses. The
      stereoselectivity of steroid action seen on vertebrate GABAA receptors was
      observed on RDL homo-oligomers as 5 alpha-pregnan-3 beta-ol-20-one (10 microM)
      was without effect. None of the three steroids tested activated currents in the
      absence of GABA. 5. The novel anticonvulsant, loreclezole (100 microM),
      potentiated the response to 10 microM GABA, but not that of saturating
      concentrations of GABA. delta-Hexachlorocyclohexane (0.1 microM to 30 microM) was
      a potent enhancer of submaximal responses to GABA of RDL. 6. The potencies of
      barbiturates and steroids on RDL homo-oligomers resemble those observed for
      several in situ insect GABA receptors, whereas those of benzodiazepine binding
      site ligands are considerably reduced. The differences in the benzodiazepine
      pharmacology of RDL homo-oligomers and native GABA receptors, may reflect roles
      of other subunits in native insect receptors.

PMID- 8882621
TI  - Increase by lysophosphatidylcholines of smooth muscle Ca2+ sensitivity in alpha
      toxin-permeabilized small mesenteric artery from the rat.
AB  - 1. Pharmacological characterization of different lysophosphatidylcholines was
      performed based on their effect on the Ca2+ sensitivity of contraction in alpha
      toxin-permeabilized rat mesenteric arteries. Furthermore, the effect of
      noradrenaline on [3H]-myristate-labelled lysophosphatidylcholine levels was
      assessed, to investigate whether lysophosphatidylcholines could be second
      messengers. 2. Palmitoyl or myristoyl L-alpha-lysophosphatidylcholine increased
      the sensitivity to Ca2+, whereas lysophosphatidylcholines containing other fatty
      acids had less or no effect. 3. L-alpha-phosphatidylcholine, L-alpha
      glycerophosphorylcholine, palmitic acid, myristic acid and choline, potential
      metabolites of lysophosphatidylcholines, did not affect contractions. 4.
      Noradrenaline (GTP was required) and GTP gamma S increased the sensitivity to
      Ca2+, and GDP-beta-S inhibited the effect of noradrenaline.
      Lysophosphatidylcholines, however, had no requirement for GTP and caused
      sensitization in the presence of GDP-beta-S. 5. Calphostin C, a relatively
      specific protein kinase C inhibitor, did not affect contraction induced by Ca2+,
      but abolished the sensitizing effect of lysophosphatidylcholine. 6. Noradrenaline
      caused no measurable changes in the levels of [3H]-myristate-labelled
      phosphatidylcholine and lysophosphatidylcholine at 30 s and 5 min stimulation. 7.
      These results suggest that lysophosphatidylcholines can increase Ca2+ sensitivity
      through a G-protein-independent, but a protein kinase C-dependent mechanism.
      However, the role for lysophosphatidylcholines as messengers causing Ca2+
      sensitization during stimulation with noradrenaline remains uncertain because no
      increase in [3H]-myristate labelled lysophosphatidylcholine could be measured
      during noradrenaline stimulation.

PMID- 8882622
TI  - Differential effects of protein kinase C inhibitors on chemokine production in
      human synovial fibroblasts.
AB  - 1. Rheumatoid arthritis is associated with the accumulation and activation of
      selected populations of inflammatory cells within the arthritic joint. One
      putative signal for this process is the production, by resident cells, of a group
      of inflammatory mediators known as the chemokines. 2. The chemokines interleukin
      8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and RANTES (regulated on
      activation normal T-cell expressed and presumably secreted) are target-cell
      specific chemoattractants produced by synovial fibroblasts in response to
      stimulation with interleukin-1 alpha (IL-1 alpha) or tumour necrosis factor alpha
      (TNF alpha). The signalling pathways involved in their production are not well
      defined. We therefore used four different protein kinase C inhibitors to
      investigate the role of this kinase in the regulation of chemokine mRNA and
      protein expression in human cultured synovial fibroblasts. 3. The non-selective
      PKC inhibitor, staurosporine (1-300 nM) significantly increased the production of
      IL-1 alpha-induced IL-8 mRNA and protein. A specific PKC inhibitor, chelerythrine
      chloride (0.1-3 microM), also caused a small concentration-dependent increase in
      IL-8 mRNA and protein production. In contrast, 3-[1-[3-(amidinothio)propyl]-3
      indoly]-4-(1-methyl-3-indolyl )- 1H-pyrrole-2,5-dione methanesulphonate (Ro 31
      8220) and 2[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3- yl)-maleimide
      (GF 109203X), two selective PKC inhibitors of the substituted bisindolylmaleimide
      family had a concentration-dependent biphasic effect on IL-1 alpha or TNF alpha
      induced chemokine expression. At low concentrations they caused a stimulation in
      chemokine production, which was especially evident at the mRNA level. At higher
      concentrations both inhibited IL-1 alpha or TNF alpha-induced chemokine mRNA and
      protein production. Ro 31-8220 was 10 fold more potent than GF 109203X, with an
      IC50 of 1.6 +/- 0.08 microM (mean +/- s.e.mean, n = 4) for IL-1 alpha induced IL
      8 production. Ro 31-8220 also inhibited the expression of IL-1 alpha or TNF alpha
      induced MCP-1 and RANTES mRNA with a similar potency. 4. The stimulatory effect
      of staurosporine is discussed in relation to the known poor selectivity of this
      inhibitor for PKC. It is proposed that activation of an isoform of PKC, possibly
      PKC epsilon or zeta, which is inhibited by higher concentrations of the
      bisinodolylmaleimides, plays a role in the regulation of chemokine expression
      induced by IL-1 alpha or TNF alpha in synovial cells. 5. The inhibition of
      chemokine production by bisindolylmaleimide compounds heralds a novel approach
      for future anti-inflammatory therapies.

PMID- 8882623
TI  - The binding characteristics of a human bladder recombinant P2X purinoceptor,
      labelled with [3H]-alpha beta meATP, [35S]-ATP gamma S or [33P]-ATP.
AB  - 1. The binding of [3H]-alpha beta meATP, [35s]-ATP gamma S and [alpha 33P]-ATP to
      a human bladder P2X purinoceptor, transiently expressed in CHO-K1 cells using the
      Semliki Forest Virus (SFV) expression system, was examined. The characteristics
      of the binding sites were compared with results obtained in rat vas deferens, a
      tissue in which the radioligands are thought to label P2X purinoceptors and in
      which the endogenous P2X purinoceptor displays high homology with the human
      bladder P2X purinoceptor. 2. In non-infected CHO-K1 cells, 100 microM ATP evoked
      only small inward currents (40 pA) in approximately 30% of the cells when studied
      by the whole-cell voltage clamp technique. In membranes prepared from either
      these non-infected cells or cells infected with SFV containing the LacZ gene (SFV
      LacZ), [3H]-alpha beta meATP bound with low affinity (pKd = 7.04; Bmax = 8.88
      pmol ml-1 protein) and there was only a low density of [35S]-ATP gamma S binding
      sites (pKd = 8.74; Bmax = 358 fmol ml-1 protein). These binding sites differed
      from those present in rat vas deferens. Thus, pIC50 values for alpha beta meATP
      (6.5) and L-beta gamma meATP (4.0) at the [3H]-alpha beta meATP binding sites in
      non-infected CHO-K1 cells were much lower than the respective pIC50 values of 8.3
      and 7.7, determined in rat vas deferens. Similarly, affinity estimates (pIC50
      values) for ATP (6.82), 2-meS-ATP (5.43), ATP gamma S (7.06) and alpha beta meATP
      (4.84) at the [35S]-ATP gamma S binding sites in non-infected CHO-K1 cells were
      up to 2291 fold lower than the respective values of 9.01, 8.79, 8.73 and 7.57,
      determined in rat vas deferens. 3. In CHO-K1 cells infected using SFV containing
      the cDNA for the human bladder P2X purinoceptor (SFV-h.P2X), ATP, 2-meS-ATP and
      alpha beta meATP evoked large inward currents (2-7 nA) in whole cell voltage
      clamp studies. In membranes prepared from these SFV-h.P2X infected cells, [3H]
      alpha beta meATP binding was increased, compared to that measured in the non
      infected or SFV-LacZ infected cells, with only high affinity [3H]-alpha beta
      meATP binding sites being detected (pKd = 9.21; Bmax = 3.54 pmol mg-1 protein).
      The pIC50 values for alpha beta meATP (8.2) and L-beta gamma meATP (7.2) in
      competing for these sites were the same or similar to the values determined in
      rat vas deferens. 4. A high density of [35H]-ATP gamma S binding sites (pKd =
      9.09; Bmax = 6.82 pmol mg-1 protein) was also present in the membranes from CHO
      K1 cells infected with SFV-h.P2X and affinity estimates (pIC50 values) for ATP
      (8.93), 2-meS-ATP (8.23), ATP gamma S (8.08), and alpha beta meATP (7.17) at
      competing for these sites were as much as 631 fold higher than the respective
      values determined in non-infected CHO-K1 cells but were close to the values
      determined in rat vas deferens. Similar data were obtained with [alpha 33P]-ATP
      as radioligand. 5. These data suggest that [3H]-alpha beta meATP, [35S]-ATP gamma
      S and [33P]-ATP label the human bladder recombinant P2X purinoceptor expressed in
      CHO-K1 cells following infection with SFV-h.P2X and provide further corroborative
      evidence to support the contention that the high affinity binding sites for these
      radioligands in rat vas deferens are P2X purinoceptors.

PMID- 8882624
TI  - Effects of tedisamil (KC-8857) on cardiac electrophysiology and ventricular
      fibrillation in the rabbit isolated heart.
AB  - 1. The direct cardiac electrophysiological and antifibrillatory actions of
      tedisamil (KC-8857) were studied in rabbit isolated hearts. 2. Tedisamil (1, 3,
      and 10 microM), prolonged the ventricular effective refractory period (VRP) from
      120 +/- 18 ms (baseline) to 155 +/- 19, 171 +/- 20, and 205 +/- 14 ms,
      respectively. Three groups of isolated hearts (n = 6 each) were used to test the
      antifibrillatory action of tedisamil. Hearts were perfused with 1.25 microM
      pinacidil, a KATP channel activator. Hearts were subjected to hypoxia for 12 min
      followed by 40 min of reoxygenation. Ventricular fibrillation (VF) developed
      during hypoxia and reoxygenation in both the control and 1 microM tedisamil
      treated groups (5/6 and 4/6, respectively). Tedisamil (3 microM) reduced the
      incidence of VF (0/6, P = 0.007 vs. control). 3. In a separate group of hearts,
      VF was initiated by electrical stimulation. The administration of 0.3 ml of 10 mM
      tedisamil, via the aortic cannula, terminated VF in all hearts, converting them
      to normal sinus rhythm. 4. Tedisamil (3 microM) reversed pinacidil-induced
      negative inotropic effects in rabbit isolated atrial muscle which were
      equilibrated under normoxia, as well as in atrial muscle subjected to hypoxia and
      reoxygenation. 5. The results demonstrate a direct antifibrillatory action of
      tedisamil in vitro. The mechanism responsible for the observed effects may
      involve modulation by tedisamil of the cardiac ATP-regulated potassium channel,
      in addition to its antagonism of IK and Ito.

PMID- 8882625
TI  - Evidence that tachykinins relax the guinea-pig trachea via nitric oxide release
      and by stimulation of a septide-insensitive NK1 receptor.
AB  - 1. This study investigated the possibility that tachykinins relax the guinea-pig
      isolated trachea by releasing nitric oxide (NO) from the epithelium. The types of
      tachykinin receptor mediating both relaxation and contraction of the trachea were
      also studied. Isometric tension was recorded in isolated tracheal tube
      preparations precontracted with acetylcholine (10 microM) in which compounds were
      administered intraluminally in the presence of phosphoramidon and indomethacin
      (both 1 microM) and the tachykinin NK2 receptor antagonist, SR 48,968 ((S)-N
      methyl-N[4-(4-acetyl amino-4-phenylpiperidino)-2-(3,4
      dichlorophenyl)butyl]benzamide), 0.1 microM). 2. In the presence of the inactive
      enantiomer of an NO-synthase inhibitor, NG-monomethyl-D-arginine (D-NMMA, 100
      microM), substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and the
      selective NK1 receptor agonist, [Sar9, Met(O2)11]-SP, (0.1-10 nM) relaxed
      tracheal tube preparations. This relaxation was changed into a contraction by
      pretreatment with the NO-synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA,
      100 microM). The effect of L-NMMA on SP- and [Sar9, Met(O2)11]-SP-induced
      responses was reversed by L-arginine (L-Arg, 1 mM), but not by D-Arg (1 mM).
      After removal of the epithelium SP, NKA and NKB and [Sar9, Met(O2)11]-SP (0.1-10
      nM) evoked contractile responses in the presence of either L-NMMA (100 microM) or
      D-NMMA (100 microM). The effects of SP and [Sar9, Met(O2)11]-SP obtained in the
      presence of another NO-synthase inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME, 100 microM) or its inactive enantiomer, NG-nitro-D-arginine methyl ester (D
      NAME, 100 microM) were similar to those observed with L-NMMA or D-NMMA,
      respectively. 3. The selective NK1 receptor agonist, [pGlu6, Pro9]-SP(6-11)
      (septide, 0.1-10 nM) evoked contractile responses of tracheal tube preparations
      in the presence of either D-NMMA (100 microM) or L-NMMA (100 microM). The log
      concentration-response curve to septide obtained in the presence of L-NMMA was
      similar to that obtained in the presence of D-NMMA. [Sar9, Met(O2)11]-SP (0.1-10
      nM) relaxed tracheal tube preparations precontracted with septide (1 microM),
      whereas septide (0.1 nM-1 microM) further contracted tracheal tube preparations
      precontracted with [Sar9, Met(O2)11]-SP (1 microM). 4. Relaxant and contractile
      responses evoked by SP, NKA, NKB and by [Sar9, Met(O2)11]-SP (0.1-10 nM) were not
      affected by a combination of the histamine H1 (pyrilamine, 1 microM) and H2
      (cimetidine, 1 microM) receptor antagonists, but were abolished by the tachykinin
      NK1 receptor antagonist, CP-99,994 ((2S,3S)-3-(2-methoxybenzylamino)-2
      phenylpiperidine, 1 microM), though not by its inactive enantiomer CP-100,263 (1
      microM). Contractile responses evoked by septide (10 nM and 1 microM) were also
      abolished by CP-99,994 (1 microM) but not by CP-100,263 (1 microM). 5. These
      results demonstrate that tachykinins relax guinea-pig tracheal tube preparations
      by releasing NO via the stimulation of epithelial NK1 receptors by a mechanism
      independent of histamine release. The NK1 receptor type involved is sensitive to
      SP, NKA, NKB and [Sar9, Met(O2)11]-SP but not to septide, and is
      pharmacologically distinct from the NK1 receptor that mediates contraction, which
      is stimulated by all the agonists, including septide.

PMID- 8882626
TI  - Characterization of endothelin receptor subtypes mediating Ca2+ mobilization and
      contractile response in rabbit iris dilator muscle.
AB  - 1. We investigated the characteristics of endothelin (ET)-induced contraction and
      changes in intracellular Ca2+ concentration ([Ca2+]i) using the fura-2-loaded and
      non-loaded rabbit iris dilator. ET-1 and ET-2 (3-100 nM) and ET-3 (30-100 nM)
      caused contraction in a concentration-dependent fashion. 2. The selective ETB
      receptor agonists, IRL1620 and sarafotoxin S6c produced only a small contraction
      or no contraction at a concentration of 1 microM. The rank order of potencies for
      the contraction (pD2 value) was ET-1 = ET-2 > ET-3 >> sarafotoxin S6c = IRL1620.
      3. The contractile response to ET-3 was antagonized by pretreatment with BQ-123
      (10 nM), a selective ETA receptor antagonist. The contractile responses to ET-1
      and ET-2 were antagonized by pretreatment with BQ-123 (10 microM), but not at a
      concentration of 10 nM. 4. ETs increased [Ca2+]i and sustained muscle
      contraction. ET-1 (100 nM), ET-2 (100 nM), and ET-3 (1 microM) induced an
      elevation of [Ca2+]i consisting of two components: first a rapid and transient
      elevation to reach a peak, followed by a second, sustained elevation; a sustained
      contraction was produced without a transient contraction. The ETB receptor
      selective agonist, IRL1620 (1 microM) and sarafotoxin S6c (1 microM) also induced
      a rapid and transient elevation of [Ca2+]i to reach a peak and a sustained
      elevation, together with only a small contraction or no contraction. 5. ET-1 (100
      nM) induced a transient increase in [Ca2+]i in a Ca(2+)-free, 2 mM EGTA
      containing physiological saline solution (Ca(2+)-free PSS), and a small sustained
      contraction which was significantly different from that induced by ET-1 (100 nM)
      in normal PSS. The ET-1-induced increase in [Ca2+]i and sustained contraction
      were not affected by the voltage-dependent Ca2+ channel blocker, nicardipine (10
      microM). The ET-1-induced transient increase in [Ca2+]i was significantly reduced
      by the sarcoplasmic reticulum (SR) Ca(2+)-ATPase inhibitor, cyclopiazonic acid
      (30 microM); however, the ET-1-induced sustained contraction was not affected by
      this agent. 6. The selective ETA receptor antagonist, BQ-123 (100 nM) reduced the
      ET-3 (100 nM)-induced contraction, but did not affect the transient increase or
      elevation of the second phase of [Ca2+]i. However, this antagonist at 1 microM
      did not affect the ET-1 (100 nM)- and ET-2 (100 nM)-induced elevation of [Ca2+]i
      and contractile response, or the IRL1620-induced elevation of [Ca2+]i. 7. The
      selective ETB receptor antagonist, BQ-788 (1 microM) reduced the transient
      increase in [Ca2+]i induced by ET-1 (30 nM), ET-2 (30 nM), ET-3 (100 nM) and
      IRL1620 (1 microM), but did not affect the sustained elevation of [Ca2+]i and
      contractile responses produced by ET-1, ET-2 and ET-3. 8. Pretreatment with
      IRL1620 (1 microM) reduced the increase in [Ca2+]i induced by IRL1620 (1 microM)
      and sarafotoxin S6c (1 microM), as well as the ET-1 (100 nM)-, ET-2 (100 nM)- and
      ET-3 (1 microM)-induced elevation of [Ca2+]i, whereas in the presence of IRL1620,
      ET-1-, ET-2- and ET-3-induced contractions were unaltered. 9. These results
      suggest that ETA and ETB receptor subtypes exist in the rabbit iris dilator
      muscle, and that the ETA receptor is divided into: (1) BQ-123-sensitive ETA
      subtypes activated by ET-1, ET-2 and ET-3, and (2) BQ-123-insensitive ETA
      subtypes activated by ET-1 and ET-2, which cause the sustained increase of
      [Ca2+]i and contraction; in contrast, ETB receptor subtypes are activated by ET
      1, ET-2, ET-3, IRL1620 and sarafotoxin S6c and cause the transient and sustained
      increase in [Ca2+]i which is not able to contract the smooth muscle.

PMID- 8882627
TI  - Modelling the changes induced by chronic desipramine treatment on the factors
      governing the agonism at prejunctional alpha 2-adrenoceptors.
AB  - 1. The adaptational changes induced after chronic desipramine treatment on
      functional responsiveness of alpha 2-adrenoceptor activation were investigated in
      prostatic portions of the rat vas deferens. 2. For this purpose, clonidine and
      xylazine were studied for their effects on twitch contractions elicited by
      electrical field stimulation of prostatic portions removed 48 h after the last
      injection to the animals of vehicle or desipramine (10 mg kg-1, i.p.; 14 days).
      Operational model-fitting and the nested hyperbolic method were used to analyse
      the effects of irreversible receptor alkylation by N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ, 300 nM) on the alpha 2-adrenoceptor-mediated effects of
      clonidine, either in vehicle- or in desipramine-treated animals. 3. Treatment
      with desipramine decreased the potency (increased the EC50) of clonidine and
      xylazine by about 12 and 9 fold respectively. However, the treatment did not
      modify the maximal effect (alpha) elicited by either agonist. The estimates of
      apparent affinity for clonidine did not depend on the method of calculation as
      the 'null' method and the 'operational' method gave similar answers. Estimates of
      tau values for both agonists revealed that chronic desipramine treatment resulted
      in significant decreases in the efficacy of agonists. However, desipramine
      treatment was not associated with significant changes in the affinity constant
      for clonidine while for xylazine, the operational model provided a higher
      estimate of KA (lower affinity) after desipramine treatment. 4. The results
      indicate a large receptor reserve at prejunctional alpha 2-adrenoceptors which is
      modulated by chronic desipramine treatment. 5. The comparison of results obtained
      after chronic desipramine exposure with those by using EEDQ suggests that chronic
      desipramine treatment is not a useful experimental intervention for the purpose
      of estimating agonist affinities and efficacies.

PMID- 8882628
TI  - Mechanisms of block of a human cloned potassium channel by the enantiomers of a
      new bradycardic agent: S-16257-2 and S-16260-2.
AB  - 1. The effects of S-16257-2 (S57) and S-16260-2 (R60), the two enantiomers of a
      new bradycardic agent, were studied on human cloned K+ channels (hKv1.5) stably
      expressed in a mouse L cell line using the whole-cell configuration of the patch
      clamp technique. 2. S57 and R60 did not modify the sigmoidal activation time
      course of the current but reduced the amplitude and increased the rate of the
      decay of the current during the application of depolarizing pulses. Both, S57 and
      R60 produced a concentration-dependent block of hKv1.5 channels with apparent KD
      values of 29.0 +/- 1.9 microM and 40.9 +/- 4.0 microM, respectively. Thus, S57
      was 1.4 fold more potent than R60 in blocking hKv1.5 channels. 3. The blockade
      produced by S57 and R60 was voltage-dependent and increased steeply between -30
      and 0 mV, which corresponded with the voltage range for channel opening. This
      result indicated that both enantiomers block the hKv1.5 channels, preferentially,
      when they are in the open state. Between 0 and +60 mV the blockade exhibited a
      shallow voltage-dependence which was described by an electrical distance of 0.18
      +/- 0.002 and 0.19 +/- 0.004 for S57 and R60, respectively. 4. S57 and R60 also
      increased the rate of decline of the current during the application of
      depolarizing pulses. The time constant of such decline (tau Block) was faster in
      the presence of R60 than in the presence of S57 (16.2 +/- 1.5 ms vs. 24.0 +/- 2.6
      ms; P < 0.01). The apparent association rate constants (k) were similar for S57
      and R60 ((0.52 +/- 0.13) x 10(6) M-1 s-1 and (0.66 +/- 0.13) x 10(6) M-1 s-1,
      respectively), whereas the dissociation rate constant (l) was faster for R60 than
      for S57 (25.8 +/- 1.8 s-1 and 13.0 +/- 2.4 s-1, respectively). 5. Both
      enantiomers slowed the deactivation of the tail currents elicited upon
      repolarization to -40 mV, thus inducing a 'crossover' phenomenon. These results
      suggested that drug unbinding is required before hKv1.5 channels can close. 6. It
      is concluded that R60 and S57 produced a similar time- voltage- and state
      dependent block of hKv1.5 channels that can be interpreted as open channel block
      by the charged form of each enantiomer. The main difference between R60 and S57
      were linked to the apparent dissociation rate constants.

PMID- 8882629
TI  - Effect of membrane hyperpolarization induced by a K+ channel opener on histamine
      induced Ca2+ mobilization in rabbit arterial smooth muscle.
AB  - 1. The role of membrane hyperpolarization on agonist-induced contraction was
      investigated in intact and alpha-toxin-skinned smooth muscles of rabbit
      mesenteric artery by use of the ATP-sensitive K+ channel opener, (-)-(3S,4R)-4-(N
      acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2- dimethyl-2H-1-benzopyran-3-ol (Y
      26763), and either histamine (Hist) or noradrenaline (NA). 2. Hist (3 microM) and
      NA (10 microM) both produced a phasic, followed by a tonic increase in
      intracellular Ca2+ concentration ([Ca2+]i) and force. Y-26763 (10 microM)
      potently inhibited the NA-induced phasic and tonic increase in [Ca2+]i and force.
      In contrast, Y-26763 attenuated the Hist-induced phasic increase in [Ca2+]i and
      force but had almost no effect on the tonic response. However, ryanodine
      treatment of muscles in order to inhibit the function of intracellular Ca2+
      storage sites altered the action of Y-26763 which now attenuated the Hist-induced
      tonic increase in [Ca2+]i and force in a concentration-dependent manner (at
      concentrations > 1 microM). Glibenclamide (10 microM) attenuated the inhibitory
      action of Y-26763. 3. Hist (3 microM) depolarized the smooth muscle cells to the
      same extent as NA (10 microM). In the absence of either agonist, Y-26763 (over 30
      nM) hyperpolarized the membrane and glibenclamide inhibited this
      hyperpolarization. Y-26763 (10 microM) almost abolished the NA-induced membrane
      depolarization, but only slightly attenuated the Hist-induced membrane
      depolarization in which the delta (delta) value (the difference before and after
      application of Hist) was not modified by any concentration of Y-26763. In
      ryanodine-treated smooth muscle cells, Y-26763 hyperpolarized the membrane and
      potently inhibited the membrane depolarization induced by Hist. 4. In ryanodine
      treated muscle, Y-26763 had no measurable effect on the Hist-induced [Ca2+]i
      force relationship. Y-26763 also had no apparent effect on the myofilament Ca(2+)
      sensitivity in the presence of Hist in alpha-toxin-skinned smooth muscles. 5. It
      is concluded that the membrane hyperpolarization induced by Y-26763 may not be
      enough to inhibit the Hist-activated Ca2+ influx. It is also suggested that Hist
      prevents the membrane hyperpolarization induced by Y-26763, activating an unknown
      mechanism which is thought to depend on the function of intracellular Ca2+
      storage sites.

PMID- 8882630
TI  - Stimulatory effects of the putative metabotropic glutamate receptor antagonist L
      AP3 on phosphoinositide turnover in neonatal rat cerebral cortex.
AB  - 1. The effects of the metabotropic glutamate receptor (mGluR) antagonist, L-2
      amino-3-phosphonopropionate (L-AP3) on phosphoinositide turnover in neonatal rat
      cerebral cortex slices has been investigated. 2. At concentrations of < or = 300
      microM, L-AP3 inhibited total [3H]-inositol phosphate ([3H]-InsPx) and
      Ins(1,4,5)P3 mass responses stimulated by the selective mGluR agonist, 1-amino
      cyclopentane-1S, 3R-dicarboxylic acid (1S, 3R-ACPD). Comparison with the
      competitive mGluR antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine ((+/-)
      MCPG) clearly demonstrated that L-AP3 caused inhibition by a mechanism that was
      not competitive, as L-AP3 decreased the maximal response to 1S, 3R-ACPD (by
      approximately 40% at 300 microM L-AP3) without significantly affecting the
      concentration of 1S, 3R-ACPD required to cause half-maximal stimulation of the
      [3H]-InsPx response. 3. In contrast, at a higher concentration L-AP3 (1 mM)
      caused a large increase in [3H]-InsPx accumulation which was similar in magnitude
      in both the absence and presence of 1S, 3R-ACPD (300 microM). D-AP3 (1 mM) had no
      stimulatory effect alone and did not affect the response evoked by 1S, 3R-ACPD. L
      AP3 (1 mM) also caused a large increase in Ins(1,4,5)P3 accumulation. The
      magnitude of the response (4-5 fold increase over basal) approached that evoked
      by a maximally effective concentration of 1S, 3R-ACPD, but differed substantially
      in the time-course of the response. The stimulatory effects of 1S, 3R-ACPD and L
      AP3 on Ins(1,4,5)P3 accumulation were also similarly affected by decreases in
      extracellular calcium concentration. 4. Detailed analysis of the inositol
      phospholipid labelling pattern and the inositol (poly)phosphate isomeric species
      generated following addition of L-AP3 was also performed. In the continued
      presence of myo-[3H]-inositol, L-AP3 (1 mM) stimulated a significant increase in
      phosphatidylinositol labelling, but not that of the polyphosphoinositides, and
      the inositol (poly)phosphate profile suggested that substantial Ins(1,4,5)P3
      metabolism occurs via both 5-phosphatase and 3-kinase routes. 5. A significant
      stimulatory effect of L-AP3 (1 mM) on [3H]-InsPx accumulation was also observed
      in neonatal rat hippocampus, and cerebral cortex and hippocampus slices prepared
      from adult rat brain. 6. These data demonstrate that whilst L-AP3 antagonizes
      mGluR-mediated phosphoinositide responses at concentrations of < or = 300 microM,
      higher concentrations substantially stimulate this response. The ability of (+/-)
      MCPG (1 mM) to attenuate significantly L-AP3-stimulated [3H]-InsPx accumulation,
      suggests that both the inhibitory and stimulatory effects of L-AP3 may be
      mediated by mGluRs.

PMID- 8882631
TI  - Regulation by metformin of the hexose transport system in vascular endothelial
      and smooth muscle cells.
AB  - 1. The effect of the biguanide metformin on hexose transport activity was studied
      in bovine cultured aortic endothelial (BEC) and smooth muscle cells (BSMC). 2.
      Metformin elevated the rate of hexose transport determined with 2-deoxyglucose
      (2DG) in a dose- and time-dependent manner in both cell types. Similar ED50
      values (0.8-1.0 mM) were determined for the effect of metformin on 2DG uptake in
      both BEC and BSMC following 24 h exposure to increasing concentrations of
      metformin, with maximal stimulation at 2 mM. 3. In BEC, metformin increased the
      hexose transport rate 2-3 fold at all glucose concentrations tested (3.3-22.2
      mM). In BSMC incubated with 22.2 mM glucose, metformin elevated the hexose
      transport approximately 2 fold. The drug was also effective at lower glucose
      levels, but did not exceed the maximal transport rate observed in glucose
      deprived cells. 4. Similar results were obtained when the effect of metformin on
      hexose transport activity was assessed with the non-metabolizable hexose
      analogue, 3-O-methylglucose, suggesting that the drug affects primarily the rate
      of hexose transport rather than its subsequent phosphorylation. 5. The metformin
      induced increase in hexose transport in BSMC treated for 24 h with the drug
      correlated with increased abundance of GLUT1 protein in the plasma membrane, as
      determined by Western blot analysis. 6. These data indicate that in addition to
      its known effects on hexose metabolism in insulin responsive tissues, metformin
      also affects the hexose transport system in vascular cells. This may contribute
      to its blood glucose lowering capacity in patients with Type 2, non-insulin
      dependent diabetes mellitus.

PMID- 8882632
TI  - Characterization of 5-hydroxytryptamine receptors mediating contractions in
      basilar arteries from stroke-prone spontaneously hypertensive rats.
AB  - 1. The 5-hydroxytryptamine (5-HT) induced-contraction in ring preparations of
      basilar arteries from Wistar-Kyoto rats (WKY) and stroke-prone spontaneously
      hypertensive rats (SHRSP) was pharmacologically characterized in vitro. 2.
      Contractile responses to 5-HT (1 nM-100 nM) and their pD2 values in arteries from
      SHRSP at 6 months of age were significantly greater than those in age-matched
      WKY, although the maximum response did not differ between the two groups. 3.
      There were no significant differences in contractile responses to U-44619,
      endothelin-1, neuropeptide Y, and angiotensin II between WKY and SHRSP arteries.
      4. Spiperone (1 nM-1 microM, a 5-HT2 receptor antagonist), produced biphasic
      displacement of the 5-HT curves in WKY and SHRSP arteries. The response to high
      concentrations of 5-HT was concentration-dependently antagonized by spiperone,
      while the response to low concentrations of 5-HT was resistant to blockade by
      spiperone, and the spiperone-resistant contractile responses induced by 5-HT were
      greater in SHRSP than in WKY. Ketanserin (1-100 nM, 5-HT2) also produced a
      biphasic shift of the 5-HT curves for both arteries. 5. Methiothepin (10 and 100
      nM, 5-HT1 and 5-HT2) potently inhibited 5-HT-induced contractions in both groups.
      In addition, methiothepin (100 nM) produced a parallel shift to the right of the
      component of 5-HT-induced contractile responses that was resistant to blockade by
      spiperone in both groups. 6. The contractile effects of 5-HT in WKY and SHRSP
      arteries were not affected by MDL 72222 (1 microM, 5-HT3) and SDZ 205-557 (1
      microM, 5-HT4). In addition, cocaine (10 microM), pargyline (50 microM), prazosin
      (10 microM), indomethacin (3 microM) and SQ 29,548 (1 microM) did not affect the
      contractile effects of 5-HT in either artery. 7. Contractile responses to 5
      carboxamidotryptamine, CGS 12066B, pindolol and propranolol were greater in SHRSP
      arteries than in WKY arteries, whereas contractions in response to 8-hydroxy-2
      (di-n-propylamino)tetralin (8-OH-DPAT), alpha-methyl-5-HT and 2-methyl-5-HT did
      not differ between the two groups. Cisapride failed to contract basilar arteries
      in both groups. Furthermore, a correlation analysis showed a highly significant
      correlation between the pD2 values of 5-HT agonists in WKY and SHRSP arteries and
      their published binding affinities at the 5-HT1B subtype. 8. These findings
      suggest that 5-HT elicits vasoconstriction in rat basilar arteries by stimulation
      of a mixed receptor population of 5-HT2 and 5-HT1-like receptors (similar to the
      5-HT1B receptor subtype), and that the contraction mediated by 5-HT1-like
      receptors is enhanced in the basilar artery from SHRSP.

PMID- 8882633
TI  - Stimulation of protein kinase C redistribution and inhibition of leukotriene B4
      induced inositol 1,4,5-trisphosphate generation in human neutrophils by lipoxin
      A4.
AB  - 1. To test the hypothesis that protein kinase C (PKC) is involved in the
      inhibitory actions of lipoxin A4 (LXA4) on second messenger generation, we
      studied the effects of LXA4 on PKC in human neutrophils and on leukotriene B4
      (LTB4)-stimulated inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) generation. 2.
      LXA4, 1 microM, caused a fall in cytosolic PKC-dependent histone phosphorylating
      activity to 23.5% of basal levels. 3. LXA4, caused an increase in particulate PKC
      dependent histone phosphorylating activity with a bell-shaped dose-response
      fashion; maximal stimulation was observed at 10 nM LXA4. 4. Western blot analysis
      with affinity-purified antibodies to alpha- and beta-PKC showed that only the
      beta-PKC isotype was translocated by LXA4. 5. LXA4 inhibited LTB4-stimulated
      Ins(1,4,5)P3 generation in a bell-shaped fashion with maximal inhibition at 1 nM
      LXA4. The observed inhibition was dose-dependently removed by pre-incubation with
      a PKC inhibitor (Ro-31-8220). 6. These results show that LXA4 activates PKC in
      whole cells and supports a role for PKC activation in the inhibitory action of
      LXA4 on LTB4-induced Ins(1,4,5)P3 generation. 7. LXA4 (1-1000 nM) pre-incubation
      did not affect specific binding of [3H]-LTB4 to neutrophils. Thus, the inhibitory
      effect of LXA4 on LTB4-stimulated Ins(1,4,5)P3 generation could not be attributed
      to an effect on LTB4 receptors.

PMID- 8882634
TI  - Stimulation by the nucleotides, ATP and UTP of mitogen-activated protein kinase
      in EAhy 926 endothelial cells.
AB  - 1. We have investigated the characteristics of activation of the 42kDa isoform of
      mitogen-activated protein (MAP) kinase in response to various nucleotides in the
      endothelial cell line EAhy 926. 2. Adenosine 5'-triphosphate (ATP) in the
      concentration range 0.1-100 microM stimulated the rapid and transient tyrosine
      phosphorylation and activation of the 42 kDa isoform of MAP kinase in EAhy 926
      endothelial cells which peaked at 2 min and returned to basal values by 60 min.
      ATP also stimulated a similar response in primary cultured bovine aortic
      endothelial cells. 3. Uridine 5' triphosphate (UTP) also stimulated the 42 kDa
      isoform of MAP kinase with similar potency to ATP (EC50 values 5.1 +/- 0.2 microM
      for UTP; 2.9 +/- 0.8 microM for ATP), whilst the selective P2Y-purinoceptor
      agonist, 2-methylthioATP (2-meSATP) was without effect up to concentrations of
      100 microM. In bovine aortic endothelial cells however, UTP and 2-meSATP both
      stimulated MAP kinase. 4. Pretreatment of cells for 24 h with 12-O tetradecanoyl
      phorbol 13-acetate resulted in the loss of the alpha and epsilon isoforms of
      protein kinase C (PKC) and virtual abolition of nucleotide-stimulated MAP kinase
      activity (> 90% inhibition). 5. Preincubation for 30 min with the PKC inhibitor,
      Ro-31 8220 (10 microM) reduced MAP-kinase activation at 2 min but potentiated the
      response at 60 min. 6. Removal of extracellular calcium in the presence of EGTA
      reduced the MAP kinase activation in response to UTP by approximately 30-50%. 7.
      Pretreatment with pertussis toxin (18 h, 50 ng ml-1) did not significantly affect
      the UTP-mediated activation of pp42 MAP kinase. 8. These results show that in the
      EAhy 926 endothelial cell line, nucleotides stimulate activation of MAP kinase in
      a protein kinase C-dependent manner through interaction with a P2U-purinoceptor.

PMID- 8882635
TI  - Calcium entry and 5-HT2 receptor blockade in oliguric ischaemic acute renal
      failure: effects of levemopamil in conscious rats.
AB  - 1. Unilateral left renal artery occlusion for 1 h in a group of 8 untreated
      female Sprague-Dawley rats resulted in oliguric acute renal failure (ARF)
      persisting for more than 6 h after reflow, i.e. after reperfusion of the kidney
      by removal of the arterial clamp. In a second group of 8 rats with left
      unilateral ARF the effects of levemopamil (L), a calcium entry blocker with 5
      hydroxytryptamine2 (5-HT2) receptor antagonistic properties, were studied. Rats
      received L as a continuous infusion (6 mg kg-1 h-1) from 1 h before ischaemia
      until 6 h after reflow. 2. Endogenous creatinine clearance, an estimate of
      glomerular filtration rate (GFR), of left ischaemic kidneys of untreated rats was
      almost completely abolished and urine flow was 0.05 +/- 0.02 and 0.03 +/- 0.01 ml
      h-1 100 g-1 body weight (body wt.) at 2 and at 6 h of reflow, respectively. In
      contrast, left ischaemic kidneys of L-treated rats revealed significantly higher
      GFR (0.10 +/- 0.02 and 0.03 +/- 0.01 ml min-1 g-1 kidney weight (k.wt.); P <
      0.01) and urine flow (0.51 +/- 0.05 and 0.15 +/- 0.04 ml h-1 100 g-1 body wt.; P
      < 0.05) at 2 and 6 h of reflow, respectively. 3. At 6 h of reflow, mitochondria
      from the cortex of left ischaemic kidneys of untreated rats showed significantly
      reduced ATP synthesis when compared to right intact kidneys (0.06 +/- 0.02 vs
      0.26 +/- 0.02 mumol ATP mg-1 protein min-1 (P < 0.01)). In contrast, in L-treated
      rats, ATP synthesis of left ischaemic kidneys was largely preserved (0.17 +/-
      0.01 mumol ATP mg-1 protein min-1). 4. Ischaemia of left kidneys resulted in a
      significant decrease in medullary Na-K-ATPase activity to 9.6 +/- 2.4 as compared
      to 20.4 +/- 3.7 mumol P(i) h-1 mg-1 protein in the intact right kidneys which was
      not prevented by L (9.4 +/- 2.4 mumol P(i) h-1 mg-1 protein). 5. In untreated
      rats the calcium content in cortical mitochondria from left ischaemic kidneys had
      risen 2 fold to 23.0 +/- 1.8 at 6 h of reflow as compared to 12.2 +/- 0.3 nmol mg
      1 protein in right intact kidneys (P < 0.01). This rise in mitochondrial calcium
      was not significantly attenuated by treatment with L (19.9 +/- 1.7 nmol mg-1
      protein). 6. The results show that L transiently converted oliguria into non
      oliguria during the early phase after reflow in ischaemic ARF, i.e. after
      reperfusion following 1 h of complete interruption of renal perfusion. The
      present data suggest indirectly that the 5-HT2-antagonistic properties of L
      rather than its calcium channel blocking action maintains GFR at low level and
      protects mitochondrial function early after reflow in this model of ischaemic
      ARF.

PMID- 8882636
TI  - Biphasic effects of the beta-adrenoceptor agonist, BRL 37344, on glucose
      utilization in rat isolated skeletal muscle.
AB  - 1. The effects of the selective beta 3-adrenoceptor agonist, BRL 37344 (BRL) on
      glucose uptake and phosphorylation (i.e. glucose utilization; GU) and glycogen
      synthesis in rat isolated soleus and extensor digitorium longus (EDL) muscle
      preparations in vitro were investigated by use of 2-deoxy-[3H]-glucose (GU) and
      [U-14C]-glucose (glycogen synthesis). 2. Low concentrations of BRL (10(-11)-10(
      9) M) significantly increased GU, with maximal increases of 30% in soleus and 24%
      in EDL at 10(-11) M. Neither the selective beta 1-adrenoceptor antagonist,
      atenolol (10(-8)-10(-6) M), nor the selective beta 2-adrenoceptor antagonist, ICI
      118551 (10(-8)-10(-6) M) had any effect on the stimulation of GU induced by 10(
      11) M BRL. 3. High concentrations of BRL (10(-6)-10(-5) M) caused significant
      inhibition (up to 30%) of GU in both soleus and EDL muscles. The inhibition of
      10(-6) M BRL was blocked completely by 10(-6) and 10(-7) M ICI 118551 in soleus,
      and by 10(-6)-10(-8) M ICI 118551 in EDL; atenolol (10(-8)-10(6) M) had no
      effect. 4. Another selective beta 3-adrenoceptor agonist, CL 316,243, also caused
      a significant stimulation of muscle GU, with maximal increases of 43% at 10(-9) M
      in soleus and 45% at 10(-10) M in EDL. The stimulation of GU declined with
      further increases in the concentration of CL 316,243, but no inhibition of GU was
      seen, even at the highest concentration (10(-5) M) tested. 5. BRL at 10(-5) M
      inhibited completely insulin-stimulated glycogen synthesis in both soleus and
      EDL, but this inhibitory effect of BRL was abolished by 10(-6) M ICI 118551. BRL
      at 10(-11) M (with or without 10(-6) M ICI 118551) had no effect on insulin
      stimulated glycogen synthesis. 6. It is concluded that: (i) low (< nM)
      concentrations of BRL stimulate GU via an atypical beta-adrenoceptor that is
      resistant to conventional beta 1-adrenoceptor and beta 2-adrenoceptor
      antagonists; (ii) the stimulation of GU is negated by the activation of beta 2
      adrenoceptors that occurs at higher (> nM) concentrations of BRL; (iii)
      inhibition of GU via beta 2-adrenoceptor activation is associated with inhibition
      of glycogen synthesis, possibly due to activation of glycogenolysis; (iv) the
      opposing effects of beta 2-adrenoceptor and atypical beta-adrenoceptor activation
      on GU suggest that in skeletal muscle these adrenoceptors are linked to different
      post-receptor pathways.

PMID- 8882637
TI  - Multiple receptors for calcitonin gene-related peptide and amylin on guinea-pig
      ileum and vas deferens.
AB  - 1. The responses of the electrically stimulated guinea-pig ileum and vas deferens
      to human and rat calcitonin gene-related peptide (CGRP) and amylin were
      investigated. 2. The inhibition of contraction of the ileum produced by human
      alpha CGRP was antagonized by human alpha CGRP8-37 (apparent pA2 estimated at
      7.15 +/- 0.23) > human alpha CGRP19-37 (apparent pA2 estimated as 6.67 +/- 0.33)
      > [Tyr0]-human alpha CGRP28-37. The amylin antagonist, AC187, was three fold less
      potent than CGRP8-37 in antagonizing human alpha CGRP. 3. Both human beta- and
      rat alpha CGRP inhibited contractions of the ileum, but this was less sensitive
      to inhibition by CGRP8-37 than the effect of human alpha CGRP. However, CGRP19-37
      was twenty times more effective in inhibiting the response to rat alpha CGRP
      (apparent pA2 estimated as 8.0 +/- 0.1) compared to human alpha CGRP. 4. Rat
      amylin inhibited contractions in about 10% of ileal preparations; this effect was
      not antagonized by any CGRP fragment. Human amylin had no action on this
      preparation. 5. Both human and rat alpha CGRP inhibited electrically stimulated
      contractions of the vas deferens, which were not antagonized by 3 microM CGRP8-37
      or 10 microM AC187. 6. Rat amylin inhibited the stimulated contractions of the
      vas deferens (EC50 = 77 +/- 9 nM); human amylin was less potent (EC50 = 213 +/-
      22 nM). The response to rat amylin was antagonized by 10 microM CGRP8-37 (EC50 =
      242 +/- 25 nM) and 10 microM AC187 (EC50 = 610 +/- 22 nM). 7. It is concluded
      that human alpha CGRP relaxes the guinea-pig ileum via CGRP1-like receptors, but
      that human beta CGRP and rat alpha CGRP may use additional receptors. These are
      distinct CGRP2-like and amylin receptors on guinea-pig vas deferens.

PMID- 8882638
TI  - In vitro translation of the full-length RNA transcript of figwort mosaic virus
      (Caulimovirus).
AB  - The circular DNA genome of FMV consists of seven tandemly arranged genes placed
      successively on a full-length RNA transcript that spans the entire circular viral
      genome. This transcript is a tentative mRNA for at least five of the six major
      conserved genes of this virus (genes I-V) that are positioned on this transcript.
      The sixth major gene (gene VI) is expressed as a separate monocistronic
      transcript. A long 5'-nontranslated leader (598 nucleotides), a small
      nonconserved gene (VII), and a short intergenic region (57 nucleotides) precede
      the five major conserved genes (I through V) on the full-length transcript. A
      reporter gene (CAT), as a separate cistron or fused in-frame, to viral cistrons
      in various downstream positions in cloned versions of the viral genome was used
      in a transcription vector to generate artificial full-length transcripts of FMV.
      When these mRNAs were translated in vitro (rabbit reticulocyte lysate system),
      the reporter gene was translated efficiently in all positions. Translation of
      internal native viral gene positioned on the full-length transcript of FMV was
      also determined (the gene VI product). These observations suggest that the full
      length FMV transcript functions as a polycistronic mRNA in plants. Results are
      best explained on the basis of translational coupling/relay race model.

PMID- 8882639
TI  - Subtle determinants of the nucleocytoplasmic partitioning of in vivo-transcribed
      RNase MRP RNA in Xenopus laevis oocytes.
AB  - RNase MRP is a ribonucleoprotein originally identified on the basis of its
      ability to cleave RNA endonucleolytically from origins of mitochondrial DNA
      replication, rendering it a likely candidate for a role in priming leading-strand
      synthesis of mtDNA. In addition, a nuclear role for RNase MRP has been identified
      in yeast (Saccharomyces cerevisiae) ribosomal RNA processing. Consistent with a
      duality of function, RNase MRP has been localized to both mitochondria and
      nucleoli by in situ techniques. The RNA component of this ribonucleoprotein has
      been characterized from several different species. We previously cloned the gene
      for Xenopus laevis MRP RNA and showed that RNase MRP RNA is differentially
      expressed during amphibian development; in addition, the microinjected X. laevis
      RNase MRP RNA gene is correctly and efficiently transcribed in vivo. This article
      presents an analysis of the intracellular movement of in vivo-transcribed RNase
      MRP RNA in microinjected mature X. laevis oocytes. Although X. laevis MRP RNA is
      assembled into a ribonucleoprotein form and transported in an expected manner,
      human and mouse MRP RNAs exhibit markedly different transport patterns even
      though they are highly conserved in primary sequence. Furthermore, the only
      currently assigned protein (Th autoantigen) binding site in MRP RNA can be
      deleted without loss of nuclear export capacity. These results indicate that
      subtle determinants must exist for nucleocytoplasmic partitioning of this RNP and
      that the conserved Th autoantigen binding region appears unnecessary for the
      transit of in vivo-transcribed MRP RNA to the cytoplasm of mature X. laevis
      oocytes.

PMID- 8882640
TI  - Differential regulation of transcription by the NURR1/NUR77 subfamily of nuclear
      transcription factors.
AB  - NURR1 is an orphan member of the nuclear receptor superfamily of transcription
      factors that shares close sequence homology to the orphan nuclear receptor and
      immediate early gene product NUR77(NGF1 beta). The physiological role of NURR1
      has not been established in mammalian cells. However, the observation that NURR1
      and NUR77 interact with at least one common enhancer element (AAAAGGTCA),
      together with their partly overlapping but differential expression patterns in
      mammalian tissues, suggests that these proteins may have both shared and
      independent transcription regulatory functions. To identify potential target
      genes that may be regulated by NURR1, we analyzed its DNA binding properties to
      potential cis-acting enhancer elements. Using point mutagenesis of the AAAAGGTCA
      motif, we have identified three additional sequences that bind specifically to
      both NURR1 and NUR77, one of which serves as a functional enhancer element.
      Comparative analysis of the transcription regulatory properties of NURR1 and
      NUR77 indicates that the proteins can display opposing transregulatory activities
      that are influenced by the specific cis-acting sequences to which they bind. Our
      results indicate that the transcriptional responses of specific target genes to
      the NURR1/NUR77 subfamily may be differentially regulated by the relative
      cellular levels of NURR1 and NUR77 and influenced by the specific enhancer
      sequences that mediate their activity. Finally, we have identified several
      potential target genes of neuronal and neuroendocrine origin whose promoters
      contain this element.

PMID- 8882641
TI  - Nuclear factor YY1 activates the mammalian F0F1 ATP synthase alpha-subunit gene.
AB  - Analysis of the promoters of the bovine and human nuclear-encoded mitochondrial
      F0F1 ATP synthase alpha-subunit genes (ATPA) has identified several positive cis
      acting regulatory regions that are important for basal promoter activity in human
      HeLa cells. We have previously determined that the binding of a protein factor,
      termed ATPF1, to an E-box sequence (CANNTG) located within one of these cis
      acting regions is critical for transcriptional activation of the ATPA gene. In
      this article, we describe a second positive cis-acting regulatory element of the
      ATPA gene that is important for expression of the ATPA gene. We show that this
      cis-acting element also contains a binding site for a protein present in HeLa
      cells. On the basis of electrophoretic mobility shift patterns, oligonucleotide
      competition assays, and immunological cross-reactivity, we conclude that this
      protein factor is Yin-Yang 1 (YY1). Experiments carried out to examine the
      functional role of YY1 within the context of the ATPA promoter demonstrated that
      YY1 acts as a positive regulator of the ATPA gene. For example, when the YY1
      binding site of the ATPA promoter was placed upstream of a reporter gene it was
      found to activate transcription in transient transfection assays. In addition,
      disruption of the YY1 binding site in the ATPA gene resulted in a loss of
      transcriptional activity. Furthermore, in cotransfection experiments
      overexpression of YY1 in trans was found to activate transcription of ATPA
      promoter-CAT constructs. Thus, at least two positive trans-acting regulatory
      factors, ATPF1 and YY1, are important for expression of the bovine and human F0F1
      ATP synthase alpha-subunit genes.

PMID- 8882642
TI  - GAL4-VP16 stimulates two RNA polymerase II promoters primarily at the
      preinitiation complex assembly step.
AB  - We previously demonstrated that RNA polymerase II promoters may be limited in
      strength not only at the step of transcription complex assembly, but also at
      initiation or promoter clearance. Here we report on experiments designed to test
      the possibility that steps following transcription complex assembly might be
      stimulated by transcriptional activators. Using an in vitro system in which we
      can independently measure the efficiency of assembly, initiation, and promoter
      clearance, we have investigated the mechanism by which the model activator GAL4
      VP16 increases transcription from two promoters: a weak variant of Ad 2 ML with
      an altered TATA box, which is inefficient in transcription initiation, and the
      mouse beta-globin promoter, which is inefficient in promoter clearance. We found
      that whereas GAL4-VP16 is effective in stimulating both promoters, this increase
      resulted only from greater transcription complex assembly; the initiation and
      clearance steps were not affected. Because recent studies have suggested that the
      core transcription factors TFIIE and TFIIH might be important in promoter
      clearance, we also attempted to increase the initiation and clearance
      efficiencies of the Ad ML-TATA mutant and globin promoters by direct addition of
      excess TFIIE and TFIIH to partially purified preinitiation complexes assembled at
      each of these promoters. These factors had no effect on transcription by either
      of the preinitiation complexes.

PMID- 8882643
TI  - In situ detection of human cytomegalovirus DNA in gastrointestinal biopsies from
      AIDS patients by means of various PCR-derived methods.
AB  - The development of new in situ assessment of HCMV disease on endoscopical
      gastrointestinal biopsies from AIDS patients is described and compared with the
      viral load measured by semiquantitative solution-phase PCR (SQ-PCR). Ten biopsies
      were examined by viral isolation, standard histology, in situ hybridization
      (ISH), in situ PCR-hybridization (PCR-ISH) and SQ-PCR, using the same target
      sequence. The methods developed for in situ HCMV detection were HCMV primers, the
      plasmid pCMV 406-S, a vector-free-digoxigenin-labelled HCMV-362 probe and the pSK
      + MCS nonsense probe. Paraffin-embedded MRC5 cells, either HCMV-infected or
      uninfected served as controls of specificity for ISH. beta-Actin primers were
      designed as markers of DNA integrity. Computerized models of the PCR, solution
      phase and in situ PCR on formalin-fixed DNA indicated that HCMV and beta-actin
      primers were efficient and specific. Nine biopsies were negative for HCMV by
      histology and virus isolation. SQ-PCR revealed 80,000; 80 and < 80 HCMV genomic
      equivalents in 6, 2 and 2 biopsies, respectively. In 8 biopsies, both ISH and PCR
      ISH identified positive nuclei in the intestinal epithelium, with sparing of the
      lamina propria. This indicates that an improvement in in situ methods can help
      the timely diagnosis of HCMV infection. Direct in situ PCR with beta-actin
      primers showed a positive signal in all the nuclei in the tissue sections,
      whereas omission of Taq polymerase resulted in an absence of signal, implying
      optimal in situ PCR. The data suggest an early-stage reactivation of HCMV,
      possibly harboured in the intestinal epithelium.

PMID- 8882644
TI  - A polymerase chain reaction to detect a spliced late transcript of human
      cytomegalovirus in the blood of bone marrow transplant recipients.
AB  - A reverse transcription (RT) nested polymerase chain reaction (PCR) procedure is
      described for detecting RNA to a spliced late gene (SLG) of human cytomegalovirus
      (CMV), the product of which (175 bp) is easily differentiated in agarose gels
      from the product when the target is unspliced viral RNA or DNA (258 bp). The SLG
      RT-PCR has been compared against a semi-quantitative PCR for CMV DNA in buffy
      coat specimens collected weekly after bone marrow transplantation from 3 patients
      and against the results of culturing these specimens for CMV both by conventional
      virus isolation, based on the detection of cytopathic effect, and by the early
      detection of infected cells by staining with virus-specific monoclonal
      antibodies. The detection of CMV RNA by SLG-RT-PCR correlated well with the
      detection of infective virus but only when the results of both culture methods
      were combined, in that neither culture method alone was as sensitive as the SLG
      RT-PCR. The presence of SLG RNA in the circulation is of value as a marker of
      active CMV infection.

PMID- 8882645
TI  - In situ hybridization technique for the detection of swine enteric and
      respiratory coronaviruses, transmissible gastroenteritis virus (TGEV) and porcine
      respiratory coronavirus (PRCV), in formalin-fixed paraffin-embedded tissues.
AB  - The in situ hybridization (ISH) technique was developed to detect the swine
      coronaviruses, transmissible gastroenteritis virus (TGEV) and porcine respiratory
      coronavirus (PRCV), in cell culture and tissue sections from TGEV-or PRCV
      infected pigs. The 35S-labeled RNA probes were generated from two plasmids
      pPSP.FP1 and pPSP.FP2 containing part of the S gene of TGEV. The procedure was
      first standardized in cell cultures. The radiolabeled pPSP.FP2 probe detected
      both TGEV and PRCV in virus-inoculated cell cultures, whereas pPSP.FP1 probe
      detected TGEV but not PRCV. The probe was then used to detect TGEV or PRCV in
      tissues of pigs experimentally infected with TGEV or PRCV or naturally infected
      with TGEV. Again, the probes detected TGEV in intestines of experimentally and
      naturally infected pigs and PRCV in the lungs of experimentally infected pigs.
      TGEV RNA was detected mainly within the enterocytes at the tips of villi and,
      less often, within some crypt epithelial cells. PRCV was shown to replicate
      mainly in the bronchiolar epithelial cells and in lesser amount in type II
      pneumocytes, type I pneumocytes, alveolar macrophages and bronchial epithelial
      cells, respectively. ISH has potential applications as a diagnostic test for the
      detection and differentiation of TGEV and PRCV in tissues and in studies to gain
      a better understanding of the mechanism of pathogenesis of enteric and
      respiratory coronavirus infections.

PMID- 8882646
TI  - Gene analysis of reassortant influenza virus by RT-PCR followed by restriction
      enzyme digestion.
AB  - An amplification system for nearly full length cDNA coding the eight influenza
      virus segments of A type (H1N1, H2N2, H3N2) and B type influenza viruses is
      described. Each of the segments of PB1, PB2, PA, NP, M, and NS can be amplified
      using one 5' primer and one 3' primer for A-type influenza viruses. The RT-PCR
      amplification system was applied to define the gene composition of three subtype
      cold-recombinant, live attenuated influenza viruses. Each segment of the
      attenuated influenza virus could be identified as deriving from segments of the
      Ca donor or wild virus by comparing the representative restriction enzyme
      digestion patterns of the three PCR products obtained from the Ca donor, the cold
      live attenuated influenza viruses and the wild virus. This RT-PCR method, using
      RT-PCR followed by digestion of PCR products with restriction enzymes, was very
      beneficial for analyzing the genome of reassortant influenza viruses.

PMID- 8882647
TI  - Mapping of polyomavirus DNA replicative intermediates by two-dimensional gel
      analysis using chemiluminescent detection.
AB  - Py DNA replicative intermediates (RIs) were mapped using a neutral/neutral two
      dimensional (N/N 2D) technique by both chemiluminescent and radioactive
      detection. The nonradioactive method provides similar sensitivity to radioactive
      methods while possessing the advantages of stability of labeled probes, faster
      processing, multiple exposures, easy disposal and safety associated with
      nonradioactive detection. Application of this method to 2D gel analysis requires
      some technical modification to reduce background and save the substrate. The
      patterns of Py RIs with Afl II digestion suggest that bidirectional replication
      occurs during Py DNA synthesis in cell culture, but other unexpected structures
      of DNA replication are also seen.

PMID- 8882648
TI  - Dengue virus envelope glycoprotein can be secreted from insect cells as a fusion
      with the maltose-binding protein.
AB  - The maltose-binding protein (MalE) contains a signal sequence which allows its
      translocation in the periplasm of prokaryotic microorganisms. In this study, MalE
      was produced in Spodoptera frugiperda (Sf9) lepidopterian cells using the
      baculovirus expression system. The secretion of MalE, following cleavage of its
      signal sequence, to the supernatant fluid of recombinant baculovirus-infected Sf9
      cells and its affinity for maltodextrin polymers allowed recovery of significant
      amounts (> or = 10 micrograms per 10(6) cells) of highly purified protein. The
      gene encoding the envelope glycoprotein E of the dengue (DEN) type 2 virus
      deleted of its C-terminal 102 amino acids (D2E delta 102) was fused to the MalE
      gene. The resulting hybrid MalE-D2E delta 102 glycoprotein was processed through
      the Golgi network of Sf9 cells and was secreted. It was retained on a
      maltodextrin column and was eluted with maltose. Antigenic and immunogenic
      properties dependent on the three-dimensional structure in the native E protein
      were preserved in the recombinant MalE-D2E delta 102 protein. Thus MalE with its
      signal sequence may be used as a carrier protein for production in the
      baculovirus system and purification of proteins which require transportation
      through intracellular compartments for correct folding and processing.

PMID- 8882649
TI  - Improved detection of barley yellow dwarf virus in single aphids using RT-PCR.
AB  - The detection of a British isolate of barley yellow dwarf virus (BYDV-G, PAV
      like) from individual vector aphids, using a combined assay of reverse
      transcription and polymerase chain reaction (RT-PCR) is reported. The method
      makes use of a multiplex format, including internal control primers directed at
      conserved regions of insect actin. The actin primers serve as controls for each
      stage of the method and are suitable for use in a range of invertebrate species.
      Detection of BYDV in vector aphids for use in forecasting systems is at present
      carried out using an enzyme-amplified ELISA system. In direct comparisons with
      the amplified ELISA, RT-PCR shows an increase in sensitivity detecting 11 fg of
      purified virus. Detection of virus in ELISA-negative aphids by RT-PCR was also
      demonstrated, and its potential as a routine diagnostic tool for virus detection
      in aphids is discussed.

PMID- 8882650
TI  - Highly sensitive immunoassays for detection of barley stripe mosaic virus and
      beet necrotic yellow vein virus.
AB  - Enzyme immunoassays based on the use of monoclonal antibodies (MAbs) were
      developed for the detection of the barley stripe mosaic virus (BSMV) and the beet
      necrotic yellow vein virus (BNYVV). Assays employing conjugates of MAbs to
      horseradish peroxidase (HRP) were compared to systems with biotinylated MAbs and
      streptavidin conjugated either to monomeric HRP or to HRP homopolymers with
      different polymerisation degrees including those of 20, 40 and 80. In the ELISA
      with streptavidin-polymeric HRP conjugates the assay detection limit was about 12
      25 times as good as in the monoclonal double antibody sandwich ELISA. The system
      for BSMV detection with polymeric HRP was sufficiently sensitive to detect a
      single infected seed among more than 10(4) healthy ones. The assay detection
      limit was 1 ng/ml. The immunoenzyme system for BNYVV allowed virus detection in
      1:12000 diluted extracts from BNYVV-infected leaves.

PMID- 8882651
TI  - A polyclonal antiserum against a recombinant viral protein combines specificity
      with versatility.
AB  - A polyclonal rabbit antiserum was obtained to the nucleoprotein of tomato spotted
      wilt tospovirus expressed as a recombinant fusion protein in E. coli. In indirect
      plate trapping ELISA, the antiserum gave similar titres against purified TSWV
      nucleocapsids in native form, the fusion protein and the carrier protein. The
      crude antiserum was also tested by Western blotting, indirect plate trapping
      ELISA and immunogold electron microscopy of thin sections: purified
      immunoglobulins were tested by DAS-ELISA. In all cases, with both glasshouse and
      field material, the antibodies had good detectability and specificity. By ELISA
      and Western blots against other tospoviruses, impatiens necrotic spot and
      groundnut bud necrosis viruses did not react but there was a reaction with
      groundnut ringspot virus, reflecting the nucleoprotein amino acid sequence
      similarity. These antibodies combine specificity to the target protein and
      versatility with regard to all the more important serological techniques. There
      were no undesired reactions resulting from immunization using a complex virus
      purified from infected host material.

PMID- 8882652
TI  - Competitive ELISA for detection of HHV-6 antibody: seroprevalence in a danish
      population.
AB  - A competitive HHV-6 enzyme-linked immunosorbent assay (ELISA) was established,
      utilizing HHV-6 rabbit polyclonal antibodies and HHV-6 cellular antigen. In
      total, 285 sera from Danish children aged 1-6 years were screened for HHV-6
      antibodies. The lowest seropositive rate, 78% was found in the youngest age group
      from 1 year to 15 months. All 120 (100%) children aged 3 years and above were
      seropositive. The ELISA was compared with indirect immunofluorescence assay (IFA)
      using a group of 83 serum samples from 65 Danish patients (aged 4 weeks to 72
      years). All but one of the sera (100% of patients) were positive in the ELISA,
      but only 71% of sera (65% of patients) were positive with both assays. The ELISA
      detected one seroconversion in a baby, which was not detected by IFA. The ELISA
      was found to be more sensitive than IFA.

PMID- 8882653
TI  - Rapid detection and typing of human papillomaviruses by consensus polymerase
      chain reaction and enzyme-linked immunosorbent assay.
AB  - A novel method for the detection and typing of human papillomaviruses (HPV) based
      on consensus polymerase chain reaction (PCR) using MY09/MY11 primers followed by
      detection of PCR products in a standard microtiter plate format using a recently
      developed commercially available standardised PCR ELISA kit (Boehringer Mannheim,
      Germany) was developed. The reliability and feasibility of the method were
      evaluated on 140 HPV-positive and 85 HPV-negative DNA samples extracted from
      different archival clinical specimens. Virtually complete agreement between the
      results of this novel method and the results of previous in-house PCRs and typing
      method was obtained. The sensitivity level of the novel method, determined by
      serial log-dilutions of SiHa cells, is about 50 copies of HPV 16. The PCR-ELISA
      provides the potential for an automated, simple, rapid and accurate test for
      detection and typing of HPV in diagnostic virological laboratories.

PMID- 8882654
TI  - Early trypsin, a female-specific midgut protease in Aedes aegypti: isolation,
      aminoterminal sequence determination, and cloning and sequencing of the gene.
AB  - Early trypsin is a female-specific protease present in the Aedes aegypti midgut
      during the first hours after ingestion of a blood meal. It plays an essential
      role in the transcriptional activation of the late trypsin form, the major midgut
      endoprotease involved in the blood meal digestion. Early trypsin is the most
      abundant midgut polypeptide isolated by benzamidine-sepharose affinity
      chromatography 3 h after feeding. The amino-terminal sequence of the early
      trypsin protein matches that of the 3a1 cDNA for a putative trypsinogen described
      by Kalhok et al. (Insect. Molec. Biol., 2, 71-79, 1993). The early trypsin cDNA
      was over expressed in Escherichia coli. Polyclonal antibodies generated against
      this recombinant protein were used to show that the enzyme was present in the
      midgut during the first 4 h after feeding. A 2.5 kb genomic clone of the early
      trypsin was isolated, mapped and subcloned. A 1.56 kb subclone, corresponding to
      1303 bp of the upstream regulatory region and 265 bp of the coding region, was
      sequenced. The gene contains a 64 nucleotide intron which interrupts the codon
      for Val at position 18 of the protein. This Val is located toward the end of the
      putative signal sequence of the protein.

PMID- 8882655
TI  - Cloning and baculovirus expression of a desiccation stress gene from the beetle,
      Tenebrio molitor.
AB  - The cDNA sequence encoding a novel desiccation stress protein (dsp28) found in
      the hemolymph of the common yellow mealworm beetle, Tenebrio molitor, has been
      determined. The sequence encodes a 225 amino acid protein containing a 20 amino
      acid signal peptide. Dsp28 shows no significant similarity to any known nucleic
      acid or protein sequence. Levels of dsp28 mRNA were found to increase approx 5
      fold following desiccation. Dsp28 cDNA has been cloned into a baculovirus
      expression vector and the expressed protein was compared to native dsp28. Both
      dsp28 expressed by recombinant baculovirus and native dsp28 are glycosylated and
      N-terminally processed. Although dsp28 is induced by cold in addition to
      desiccation stress, it does not contribute to the freezing point depression
      (thermal hysteresis) observed in Tenebrio hemolymph.

PMID- 8882656
TI  - Differences in environmental temperature, ethanol and sucrose associated with
      enzyme activity and weight changes in Drosophila melanogaster.
AB  - Activity changes of three enzymes (ADH, ODH and AOX) of Drosophila melanogaster
      were followed under different environmental conditions. The influences of
      ethanol, starvation (no carbohydrates in the medium) and ethanol stress during
      starvation were studied at both 18 and 26 degrees C. Two strains that were
      monomorphic for different alleles at the Odh and Aldox loci but otherwise
      identical were used. The investigated environmental conditions affected ADH
      induction by exogenous ethanol differently in the two strains. The different
      allozymes of ODH and AOX also responded differently to the treatments. We
      observed that the sucrose content of the medium on which ethanol exposure took
      place and the temperature strongly affected the responses within any single
      strain. Correlations were estimated among the three enzymes in the larval and
      adult stages of each strain separately. At both temperatures, differences between
      strains were observed in the patterns of associations of the response variables,
      in the larval, but not in the adult stages.

PMID- 8882657
TI  - Endocytosis by digest cells of the cattle tick Boophilus microplus: regulation by
      protein kinase C.
AB  - Endocytosis of fluorescently-labeled bovine serum albumin by digest cells of the
      gut of the cattle tick Boophilus microplus is inhibited by approx 60% in the
      presence of the tumour promoter 12-O-tetradecanoylphorbol 13-acetate. The results
      are consistent with a role for protein kinase C in regulating the uptake of blood
      meal by digest cells. Protein kinase C activity has been measured in the digest
      cell and the amount of enzyme has also been determined using a phorbol ester
      binding assay. The presence of a small number of specific protein kinase C
      substrates in the plasma membrane of the digest cell has been demonstrated.
      Preliminary experiments indicate that one of these substrates, a protein of
      approximately 30 kDa, is an integral membrane protein, part of which is exposed
      on the extracellular surface of the digest cell.

PMID- 8882658
TI  - Ecdysone and insect immunity: the maturation of the inducibility of the
      diptericin gene in Drosophila larvae.
AB  - The developmental analysis of the inducibility of the Drosophila diptericin gene
      promoter as a response to septic injury shows an important increase in the
      response during the third larval instar leading to a maximum in late larvae and
      early prepupae. This increase, or maturation, is temporally correlated with known
      ecdysone induced events of the salivary gland and we now present evidence, using
      wild type and mutant larvae, that it does indeed depend upon ecdysone. The
      response remains minimal in larvae carrying either the temperature sensitive
      ecdysone deficient late larval lethal allele ecd1, or l(1)t187, a deep orange
      allele known to be deficient in the ecdysone response. However, experiments with
      the late larval lethal Broad-Complex mutant l(1)t435 show that the regulation of
      this response is distinct from the developmental ecdysone regulated hierarchies.

PMID- 8882659
TI  - Cyclic AMP is a requisite messenger in the action of big PTTH in the prothoracic
      glands of pupal Manduca sexta.
AB  - Prothoracicotropic hormone (PTTH), a peptide produced by the insect brain,
      stimulates the prothoracic glands to secrete ecdysteroids. The big form of this
      peptide (25.5 kDa) has been postulated to act through cyclic AMP in larval
      Manduca sexta, but the role of the cyclic nucleotide in the action of PTTH in
      pupal glands has been less clear. Results of the present study indicate that PTTH
      stimulated ecdysteroid secretion and protein phosphorylation by glands removed
      from pupal Manduca sexta are blocked by two inhibitors of cAMP-dependent protein
      kinase: Rp-cAMPS, an antagonist of cAMP binding to the regulatory subunit of the
      kinase, and H-89, an inhibitor of the catalytic subunit of the kinase. Further,
      PTTH stimulates significant accumulation of cAMP in pupal glands, although less
      than that previously seen in PTTH-stimulated larval glands. Cyclic AMP-dependent
      protein kinase is found in cytoplasmic and membrane-associated glandular
      subfractions, as measured by incorporation of [32P]8-N3cAMP into the regulatory
      subunit of the kinase. PTTH enhances cytoplasmic cAMP content and appears to
      increase the amount of cAMP bound to a cytoplasmic type II regulatory subunit of
      cAMP-dependent protein kinase. The results indicate that cAMP plays a requisite
      role in PTTH action in pupal glands, thus arguing in favor of a uniform mechanism
      of action for the peptide during Manduca development.

PMID- 8882660
TI  - PCR differential display of immune gene expression in Trichoplusia ni.
AB  - The immune state of insects is defined by a set of proteins that is absent in the
      naive state. To explore the immune system of Trichoplusia ni in more detail we
      have employed a PCR differential display technique to compare the mRNA population
      of untreated last instar larvae to that of immunized animals. In the primary
      display, more than one hundred bands seemed induced upon bacterial challenge.
      When they were used as probes in Northern blots, 35% of these probes detected
      inducible mRNA species. Such probes were used to screen a cDNA library from
      immunized larvae. We isolated clones for T. ni homologs of cecropin A, lysozyme
      and attacin. One differentially expressed band hybridized to clones for BJHSP1, a
      hemacy-anin-related protein which is hormonally up-regulated in last instar
      larvae; this induction is probably not related to the bacterial infection. Still
      other probes recognized inducible mRNAs of 1.6 and 1.0 kb. The corresponding cDNA
      clones did not show strong sequence homology to any known proteins. We have
      demonstrated the potential of this PCR technique to display both known and
      unknown genes specific for the immune state of whole insects against a background
      of genes involved in larval development.

PMID- 8882661
TI  - Identification of PBAN-like peptides in the brain-subesophageal ganglion complex
      of lepidoptera using Western-blotting.
AB  - An immunoblotting technique used to visualize pheromone-biosynthesis-activating
      neuropeptide (PBAN)-like peptides in insect tissues is described. This technique
      involves a tricine-SDS-PAGE system and a chemiluminescent revelation of the
      antigens. Using this technique, PBAN-like immunoreactive peptides were found in
      the brain-subesophageal ganglion complex of various lepidopteran species,
      including moths: Heliothis zea, Mamestra brassicae, Spodoptera littoralis, S.
      latifascia and S. descoinsi (Noctuidae), Eldana saccharina (Pyralidae), and a
      butterfly: Pieris brassicae (Pieridae). PBAN-like peptides were detected in both
      sexes of the species studied, and even in a butterfly species that does not use
      pheromone to mate. This suggests that those peptides are widely distributed among
      Lepidoptera and confirms that they could be involved in functions other than
      regulation of sex pheromone production.

PMID- 8882662
TI  - Studies of HIV-1 envelope glycoprotein-mediated fusion using a simple
      fluorescence assay.
AB  - OBJECTIVE: To study HIV envelope glycoprotein (Env)-mediated entry using a
      sensitive fusion assay. DESIGN AND METHODS: CD4+ lymphocytes or T-cell lines were
      labelled with fluorescent cytoplasm or membrane markers. Fusion with Env
      expressing adherent cells was monitored by observing dye transfer from CD4+ cells
      to Env cells. RESULTS: Cell-cell fusion began 20-30 min after co-cultivation at
      37 degrees C. Pre-binding at 4 degrees C was observed not to decrease the lag
      phase before fusion. Cells expressing envelope glycoproteins from non-syncytium
      inducing (NSI) HIV strains showed dye transfer between two cells without
      progression to syncytia. A glycosylphosphatidylinositol anchored Env was found to
      be incapable of mediating membrane fusion, as measured either by lipid or
      cytoplasm contents mixing. Primary mouse cells expressing human CD4 and mouse 3T3
      cells stably expressing both human CD4 and human CD26 did not support fusion with
      our Env-expressing cells. CONCLUSIONS: Env-mediated cell-cell fusion is a
      relatively slow process, probably reflecting a multi-step process occurring after
      CD4 binding and requiring the transmembrane domain of gp41. Env proteins are able
      to mediate cell-cell fusion at least under some experimental conditions,
      indicating that lack of a syncytia phenotype does not rule out the possibility of
      fusion occurring between only two or a few cells.

PMID- 8882663
TI  - Cytotoxic T-lymphocytes from HIV-infected individuals recognize an activation
      dependent, non-polymorphic molecule on uninfected CD4+ lymphocytes.
AB  - OBJECTIVES: Correlation of lysis of autologous CD4+ target cells by cytotoxic
      lymphocytes from HIV-seropositive patients to target activation, viral
      replication, and major histocompatibility complex (MHC) restriction. DESIGN:
      Twenty-two HIV-infected patients were evaluated for lysis of activated CD4+
      cells, concurrent with measurement of proliferation of the target cells, and with
      viral replication. METHODS: Titrated standard 51Cr-release assays for specific
      effector-to-target cell recognition, blocking antibodies and cell depletion for
      cell characterization, incorporation of [3H]-thymidine for proliferation, and p24
      antigen capture assays for viral replication. RESULTS: HIV-infected patients had
      cytotoxic lymphocytes capable of recognizing activated CD4+ target cells in a non
      MHC-restricted manner. The lysis depended on the degree of target activation, and
      was independent of viral replication. CONCLUSIONS: This cytolytic activity is
      unique to HIV-infected patients, and is suggestive of activation-induced cell
      death that may contribute to the progressive depletion of CD4+ lymphocytes during
      HIV pathogenesis.

PMID- 8882664
TI  - Predictive value of viral load measurements in asymptomatic untreated HIV-1
      infection: a mathematical model.
AB  - OBJECTIVE: To model the predictive value of viral load measurements in
      asymptomatic patients with HIV-1 infection, who have CD4 cell counts > 500 x
      10(6)/l and no prior antiretroviral therapy, when the time of seroconversion and
      the prior levels of viremia are unknown. DESIGN: A mathematical model was
      constructed for the changes in HIV RNA load over time based on data from cohorts
      of HIV-infected patients followed since the time of seroconversion. METHODS: For
      different values of viral load, the time to progression to AIDS or an equivalent
      state [progression to AIDS equivalent (PAE)] was calculated using a wide range of
      estimates for the time since seroconversion and the rate of change of the viral
      load over time. RESULTS: In the absence of antiretroviral treatment, patients
      with a viral load of 10(5) copies/ml serum are at risk for PAE in less than 3
      years (0-3 years) and patients with a viral load half a log higher are at risk in
      less than 1 year. In contrast, patients with a viral load of 10(4.5) have at
      least 1.9 years and may have up to 8 years before risk of PAE. Patients with a
      viral load of 10(4) RNA copies/ml have at least 2.8 years and may have up to 19
      years before risk of PAE. The rate of change of the viral load was an important
      predictor of outcome; the time since seroconversion had only a minor effect.
      CONCLUSIONS: The viral load in the plasma or serum has predictive value even if
      the time of seroconversion is unknown. The rate of change of viral load over time
      may also be an important predictive factor. Serial measurements of viral load
      over time may provide therapeutic guidance.

PMID- 8882665
TI  - Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients
      receiving long-term continuous versus intermittent fluconazole therapy.
AB  - OBJECTIVE: To examine the impact of continuous versus intermittent fluconazole
      therapy on fungal colonization and fluconazole resistance in the oropharynx of
      HIV-infected patients. DESIGN: Case-control study. SETTING: Duke University Adult
      Infectious Diseases Clinic, a tertiary referral center in North Carolina which
      provides care for 700 HIV-infected persons. PATIENTS: Nineteen HIV-infected
      patients on daily continuous fluconazole for a minimum of 6 months and eleven HIV
      infected patients on intermittent fluconazole for a minimum of 6 months were
      matched by sex and CD4 cell count to HIV-infected patients who had not received
      fluconazole in the preceding 6 months. MAIN OUTCOME MEASURES: Fungal isolation
      and fluconazole susceptibility testing were performed on oral saline rinses from
      each patient. RESULTS: The patients taking continuous fluconazole were more
      likely than matched controls to have had sterile mouth rinses (14 out of 19
      versus five out of 19; P < 0.001), and the yeasts that were isolated were more
      likely than matched controls to be non-Candida albicans species and to have
      minimum inhibitory concentrations (MIC) to fluconazole > or = 16 micrograms/ml.
      None of these isolates were associated with symptoms. In contrast, none of the
      patients in the intermittent fluconazole group had sterile cultures. When this
      group was compared to controls, they were more likely to have had non-C. albicans
      species, and the C. albicans isolates obtained had higher MIC to fluconazole.
      CONCLUSIONS: Long-term continuous therapy with fluconazole may prevent the
      appearance of Candida in the oral cavity. This finding may reduce recurrence
      rates and might favorably impact on the clinical appearance of mucosal
      candidiasis with resistant C. albicans.

PMID- 8882666
TI  - Predictors of survival in HIV-infected tuberculosis patients.
AB  - OBJECTIVE: To ascertain predictors of survival in HIV-infected tuberculosis (TB)
      patients. DESIGN: Retrospective cohort study. SETTING: New York City public
      hospital. PATIENTS: Fifty-four consecutive HIV-seropositive patients with newly
      diagnosed TB and no other AIDS-defining illnesses. MAIN OUTCOME MEASURES: CD4+ T
      lymphocyte counts, completion of anti-TB therapy, repeat hospitalizations with
      TB, and survival. RESULTS: Forty-five (84%) of the 54 patients died a median of
      15 months after TB diagnosis (range, 1-80 months), five (9%) were alive after a
      median of 81 months (range, 75-84 months), and four (7%) were lost to follow-up
      after a median of 42 months (range, 30-66 months). In univariate analyses,
      disseminated TB, intrathoracic adenopathy, oral candidiasis and CD4 count
      depletion were each associated with decreased survival. In a multivariate
      analysis, CD4 count depletion was the only independent predictor of decreased
      survival. Repeat hospitalization with TB occurred in 10 out of 15 patients who
      did not complete anti-TB therapy compared with one out of 21 patients who
      completed anti-TB therapy (P < 0.001). CONCLUSION: The clinical presentation of
      TB and CD4 count at TB diagnosis are each predictive of survival in HIV
      seropositive TB patients. The CD4 count is the only independent predictor of
      survival.

PMID- 8882669
TI  - Increasing the use of bleach and condoms among injecting drug users in Denver:
      outcomes of a targeted, community-level HIV prevention program.
AB  - OBJECTIVE: To evaluate the impact of an HIV risk-reduction program among
      injecting drug users (IDU) in Denver, Colorado. DESIGN: A targeted, community
      level intervention study with multiple, time-phased, cross-sectional measurements
      assessing HIV high-risk behaviors among IDU in intervention and comparison sites.
      SETTING: Neighborhoods with high IDU prevalence in Denver, Colorado (intervention
      site) and Long Beach, California (non-intervention comparison site).
      PARTICIPANTS: Street-recruited IDU who had injected drugs in the previous 30 days
      and shared injection equipment in the previous 60 days to evaluate the use of
      bleach to clean injection equipment; or had sexual intercourse in the previous 30
      days, to evaluate condom use. INTERVENTION: A prevention program in which peer
      volunteers were recruited and trained to distribute and discuss intervention kits
      that included condoms, bleach bottles and role model stories. MAIN OUTCOME
      MEASURES: Multiple cross-sectional surveys were conducted in the intervention and
      comparison sites to assess the impact of the intervention on the consistent use
      of bleach before sharing injection equipment and the consistent use of condoms
      for vaginal intercourse with steady and occasional partners. RESULTS: Between
      February 1991 and December 1993, 1997 IDU were interviewed, 890 at the
      intervention site and 1107 at the comparison site. In contrast to the comparison
      site, subjects from the intervention site reported significant increases in
      consistent use of bleach [odds ratio (OR), 2.6; 95% confidence interval (CI), 1.3
      5.1; P < 0.001], and consistent use of condoms with occasional partners (OR,
      13.6; 95% CI, 3.2-58.0; P < 0.001). CONCLUSION: This targeted, peer-based
      intervention was associated with significant HIV risk reduction among IDU in
      Denver and may be useful in other communities at risk for HIV infection.

PMID- 8882668
TI  - Production of plasminogen activator and plasminogen activator inhibitors by
      alveolar macrophages in control subjects and AIDS patients.
AB  - OBJECTIVE: To reveal a possible impairment of the plasminogen activator system in
      the pulmonary infections of AIDS patients. DESIGN: To test the plasminogen
      activator system functionality in alveolar macrophages and bronchoalveolar lavage
      fluid (BALF) in control subjects and AIDS patients. Procedures were designed to
      detect the presence of imbalance in plasminogen activator activity and to
      ascertain if this imbalance is due to a direct effect of the HIV virus on
      macrophages or to superimposed opportunistic infection. METHODS: Alveolar
      macrophages obtained by bronchoalveolar lavage (BAL) were either lysed with
      Triton X-100 or cultured for 24 h. Plasminogen activators and plasminogen
      activator inhibitors (PAI) were measured by chromogenic substrate assay and
      binding to 125I-urokinase followed by 10% sodium dodecyl-sulphate polyacrylamide
      gel electrophoresis (SDS-PAGE), respectively. RESULTS: Plasminogen activator
      activity in BALF and in alveolar macrophages from AIDS patients was decreased.
      This reduction was independent of the presence of an infectious pulmonary
      process. In contrast, free PAI was increased in AIDS patients with Pneumocystis
      carinii infection. This increase is possibly caused by a different glycosylated
      form of PAI-2. CONCLUSIONS: Our data support the view that the pulmonary
      fibrogenic response is in part secondary to an imbalance within the plasminogen
      activator system and provide the basis for clarifying the role of these
      alterations in the pathophysiology of AIDS-related pulmonary infections.

PMID- 8882667
TI  - Association of maternal drug use during pregnancy with maternal HIV culture
      positivity and perinatal HIV transmission.
AB  - OBJECTIVE: To evaluate the relationship of drug use with maternal HIV culture
      positivity at delivery and perinatal HIV transmission. DESIGN: Multicenter
      prospective cohort study. SETTING: Obstetric and pediatric clinics in five cities
      in the United States. PARTICIPANTS: Five hundred and thirty HIV-infected pregnant
      women and their infants. MAIN OUTCOME MEASURES: Multivariate logistic regression
      was used to evaluate the association of 'hard drug' use (one or more of the
      following: cocaine, heroin/opiates, methadone, injecting drug use) assessed by
      self-report and urine toxicology with positive maternal HIV culture at delivery
      and perinatal HIV transmission. RESULTS: Forty-two per cent of women used hard
      drugs during pregnancy. Increased probability of a positive maternal delivery HIV
      culture was significantly associated with prenatal hard drug use [odds ratio
      (OR), 3.08] and maternal cocaine use (OR, 2.98) among HIV-infected women with >
      29% CD4+ lymphocytes. After adjusting for maternal culture positivity at
      delivery, CD4+ lymphocyte percentage and gestational age, significantly greater
      transmission risk was observed with hard drug use among women with membrane
      rupture > 4 h. CONCLUSIONS: On the basis of self-report and urine toxicology,
      overall maternal hard drug use and cocaine use in the WITS cohort were associated
      with maternal HIV culture positivity at delivery, and maternal hard drug use was
      associated with perinatal transmission.

PMID- 8882670
TI  - An epidemiological study of tuberculosis and HIV infection in Tanzania, 1991
      1993.
AB  - OBJECTIVE: In Tanzania during the past 6 years reported tuberculosis (TB) cases
      have nearly doubled, with proportionately much greater increases in smear
      negative and extrapulmonary cases compared with smear-positive cases. At the same
      time, HIV infection has become widespread throughout the country. This survey was
      undertaken in order to study the association of TB and HIV and to determine the
      impact of HIV on present and future TB cases in Tanzania. METHODS: The survey
      design provided for HIV testing of a representative country-wide sample of
      approximately one-sixth of all new and relapse cases registered between January
      1991 and December 1993, with linkage to demographic, clinical and bacteriological
      data for these cases. HIV surveillance data were used for comparison purposes.
      RESULTS: A total of 6928 TB cases from all of the country's 20 mainland regions
      were tested. The overall HIV seroprevalence was 32%. Both crude and adjusted odds
      ratios (OR) for HIV infection were higher in women, those aged 25-44 years, urban
      residents, cases of smear-negative and extrapulmonary disease, and persons with a
      bacille Calmette-Guerin (BCG) vaccination scar. The age-and sex-adjusted relative
      risk for HIV infection in TB patients compared to blood donors in the same
      regions was 7.1 (95% confidence interval, 6.6-7.5), and was significantly higher
      among those aged 25-34 years. Of 3360 patients with bacteriological culture
      results 46% were culture-positive for Mycobacterium tuberculosis. Drug
      susceptibility tests were performed on 1164 isolates with the overall rate of
      drug resistance of 6.2%. Rates of initial resistance were low in both HIV
      positive (4%) and HIV-negative (5.8%) patients. Rates of acquired resistance were
      higher (19% overall) and did not vary significantly by HIV serostatus. Initial
      combined resistance to both isoniazid and rifampicin was uncommon (0.4%) as was
      monoresistance to rifampicin (0.3%). CONCLUSIONS: The higher OR for women and
      young adults reflect the higher rates of HIV infection in those populations. The
      finding that smear-positive relapse cases were no more likely to have HIV
      infection than new smear-positive cases suggests that the treatment regimen for
      new cases is effective in HIV-associated TB. The low rates of both initial and
      acquired drug resistance in HIV-positive patients is further evidence of adequacy
      of treatment. The higher relative risk for HIV infection among patients aged 25
      34 years suggests increased HIV-related TB transmission. Finally, it is estimated
      that approximately two-thirds of the increase in the rate of smear-positive
      tuberculosis in the country can be directly attributed to HIV infection.

PMID- 8882671
TI  - Frontloading: a risk factor for HIV and hepatitis C virus infection among
      injecting drug users in Berlin.
AB  - OBJECTIVE: To determine whether frontloading (i.e., syringe-mediated drug
      sharing) is a risk factor for HIV, hepatitis B virus (HBV) and hepatitis C virus
      (HCV) infection among injecting drug users (IDU). DESIGN: Cross-sectional study.
      Data on sociodemographic and behavioural characteristics were obtained by a
      standardized questionnaire. Serum samples were tested for seromarkers for HIV,
      HBV and HCV. SETTING AND PARTICIPANTS: IDU were recruited at 'low-threshold'
      storefront agencies (out-of-treatment sample), and at a centre for long-term drug
      use treatment (in-treatment sample). Individuals were included in the study if
      they had injected drugs within the previous 3 months. MAIN OUTCOME MEASURES:
      Serological evidence for HIV, HBV, HCV exposure. RESULTS: Of all IDU (n = 324),
      84% had ever practised frontloading with non-sterile injecting equipment, and 46%
      had done so more than 100 times; 32% had front-loaded during the 6 months prior
      to the interview. The crude seroprevalence rates for HIV, HBV and HCV increased
      with the overall frequency of frontloading, and reached 22, 71 and 94%,
      respectively, among IDU who had frontloaded more than 100 times. After
      controlling for confounding effects by logistic regression, having practised
      frontloading more than 100 times was significantly associated with HIV infection
      [adjusted prevalence odds ratio (POR) 3.5; 95% confidence interval (CI), 1.4-9],
      and HCV infection (adjusted POR, 5.4; 95% CI, 2.3-12), but not with HBV
      infection. Another independent risk factor for all three virus infections was
      needle-sharing in prison. CONCLUSIONS: In communities where sterile injection
      equipment is readily available, and IDU have substantially reduced their overall
      levels of needle-sharing, the practice of frontloading appears to be a major risk
      factor for infections by blood-borne viruses among IDU. Prevention activities
      should specifically address this risk behaviour.

PMID- 8882672
TI  - Evaluation of an HIV risk reduction intervention among African-American
      homosexual and bisexual men.
AB  - OBJECTIVE: To provide the first data which evaluates an HIV risk reduction
      intervention designed to reduce HIV high-risk sexual behavior in African-American
      homosexual and bisexual men. SUBJECTS: Participants (n = 318) were recruited from
      bars, bathhouses, and erotic bookstores, and through homosexual African-American
      organizations, street out-reach, media advertisements, and personal referrals of
      individuals aware of the study. METHODS: Participants were randomized into a
      single or triple session experimental group or a wait-list control group. Both
      experimental interventions included AIDS risk education, cognitive-behavioral
      self-management training, assertion training, and attempts to develop self
      identity and social support. Data collection involved assessments of self
      reported changes in sexual behavior at 12- and 18-month follow-up. RESULTS:
      Participants in the triple session intervention greatly reduced their frequency
      of unprotected anal intercourse (from 46 to 20%) at the 12-month follow-up
      evaluation and (from 45% to 20%) at the 18-month follow-up evaluation. However,
      levels of risky behavior for the control group remained constant (from 26 to 23%
      and from 24 to 18%) at 12- and 18-month follow-up evaluations, respectively. In
      addition, levels of risky behavior for the single session intervention decreased
      only slightly (from 47 to 38% and from 50 to 38%) at the 12- and 18-month follow
      up evaluations, respectively. CONCLUSIONS: Results were interpreted to
      demonstrate the superiority of a triple session over a single session
      intervention in reducing risky sexual behavior in this cohort.

PMID- 8882673
TI  - Knowledge, attitudes and perception of AIDS in rural Senegal: relationship to
      sexual behaviour and behaviour change.
AB  - OBJECTIVES: To describe the determinants of 'at risk' sexual behaviour and
      perception of AIDS-related prevention messages in rural Africa. SETTING: A rural
      area in Southern Senegal. DESIGN: Cross-sectional study using a standardized
      questionnaire administered by local interviewers to 240 men and 242 women aged 15
      59 years, randomly selected among the general population. RESULTS: Twenty-eight
      per cent of the sexually active men and 27% of the sexually active women declared
      at least one casual sexual partner in the 12 months preceding the interview.
      Among these, 27% of men and 30% of women declared having used a condom in most
      acts of casual intercourse. Seasonal migrants and divorced or widowed women were
      more likely to declare casual sex. Causal sex was motivated by material needs for
      66% of the women who experienced it, and those of the women who reported casual
      sexual intercourse were less likely to feel at risk of AIDS [odds ratio (OR),
      3.9; P = 0.01] and were more optimistic about their future (OR, 3.6; P = 0.03).
      For men, the motivations explaining a change in sexual behaviour in order to
      avoid HIV infection included the perception of AIDS as a health problem (OR, 11;
      P = 0.004), the perception of the disease as serious (OR, 5.4; P = 0.001) and the
      feeling of personal risk of becoming HIV-infected (OR, 3.2; P = 0.02). Perceived
      skill in changing one's behaviour was strongly associated with declaration of
      past behaviour change for both men and women (men: OR, 3.4; P = 0.02; women: OR,
      6.3; P = 0.0001). CONCLUSION: Men and women exhibit two different patterns
      regarding their behaviour and perception towards AIDS. Material needs appear to
      be of importance for women, whereas perception of a real threat lead men to adopt
      protective behaviours. In the very area of this study, widowed and divorced women
      as well as male seasonal migrants are particularly exposed to HIV infection. They
      are characterized by a higher risk behaviour, a low rate of condom use and seldom
      declared any protective measures to avoid HIV infection.

PMID- 8882675
TI  - Hope for evidence-based HIV/AIDS prevention?

PMID- 8882674
TI  - Relationship between fluconazole dosage regimens and the emergence of fluconazole
      resistant Candida albicans.

PMID- 8882676
TI  - Poststenotic cavitating pneumonia due to Rhodococcus equi in HIV infection.

PMID- 8882677
TI  - Symptomatic leiomyoma of the adrenal gland in a woman with AIDS.

PMID- 8882678
TI  - Cutaneous reactions to trimethoprim-sulphametrole in AIDS patients treated for
      Pneumocystis carinii pneumonia.

PMID- 8882679
TI  - Diagnostic HIV antibody testing in the United States: the role of private
      providers and public programs.

PMID- 8882680
TI  - Presence of HIV-1 group O infection in West Africa.

PMID- 8882681
TI  - Lower prevalence and incidence of HIV-1 syncytium-inducing phenotype among
      injecting drug users relative to homosexual men.

PMID- 8882682
TI  - Cytomegalovirus infection: a possible cause of recurrent transient neurological
      dysfunction in advanced HIV infection.

PMID- 8882683
TI  - Evaluating behavioral interventions for HIV prevention.

PMID- 8882684
TI  - Identification of a novel HLA-A25-restricted epitope in a conserved region of p24
      gag (positions 71-80).

PMID- 8882685
TI  - Evaluation of oligonucleotide probes for the determination of the two major HIV-1
      env subtypes in Thailand.

PMID- 8882686
TI  - Postnatal development and structure of the neurocentral junction. Its relevance
      for spinal surgery.
AB  - STUDY DESIGN: The early and late development of the neurocentral junction between
      the vertebral arch and the vertebral body was studied, and this structure was
      related to spinal surgery. OBJECTIVES: Because of its strategic position within
      the vertebral body, its structure could be of relevance for spinal surgery.
      During the positioning of cannulated pedicle screws and before penetration into
      the cancellous bone of the vertebral body, resistance had to be overcome inside
      the "pedicle" of the vertebral arch. Was this point of resistance related to the
      neurocentral joint? SUMMARY OF BACKGROUND DATA: Data on the fate of this
      developmental structure after age 3-6 years, the age at which it fuses, appeared
      to be missing in literature. METHODS: We examined dry bone and "fresh" vertebrae
      from individuals ranging in age from 0 to 75 years. Observations were recorded by
      means of gross anatomic photographs, micrographs, radiographs, and computed
      tomography scans. RESULTS: After fusion of the junction at age 3-6 years, its
      structure persists through life as a bilateral plate of bone extending from the
      cranial to the caudal anular epiphyses inside the dorsolateral parts of the
      definitive body. CONCLUSIONS: This plate may function as a support for pedicle
      screw fixation. Its form explains typical burst fractures of the vertebral body.
      Spondylolysis at this site is unknown.

PMID- 8882687
TI  - Comparisons of lordotic cervical spine curvatures to a theoretical ideal model of
      the static sagittal cervical spine.
AB  - STUDY DESIGN: Measurements from lateral cervical radiographs of randomly selected
      patients are compared with two proposed ideal models. OBJECTIVES: To evaluate
      lordotic cervical curvatures from a large population base, to provide a geometric
      sagittal cervical spine model, and to test the validity of the model to predict
      measured angles and distances. Averages of ranges and normal values for cervical
      lordosis under conditions of static equilibrium are sought. SUMMARY OF BACKGROUND
      DATA: Seven angles and three distances were taken from 400 randomly selected
      lateral cervical radiographs of patients at a private clinic. METHODS: The
      radiographic measurements are compared with predicted values from our geometric
      sagittal cervical spine model and the Delmas ideal cervical model. RESULTS:
      Values were predicted successfully by the geometric model with an average error
      of 5% compared with the radiographic measurements. The range of lordosis,
      measured at the posterior of C2 and C7, was 16.5-66 degrees, with a mean of 34
      degrees. The average height-to-length ratio for the cervical spine was 0.97.
      CONCLUSIONS: Predicted values from the geometric model were comparable with the
      measurements of the relative rotation angles at each vertebral interspace,
      absolute rotation angles from C2 to C7, and height-to-length ratios. A cervical
      lordosis of 34 degrees and a height-to-length ratio of 0.97 are suggested for
      clinical and theoretical outcomes.

PMID- 8882688
TI  - Kinematic evaluation of lumbar fusion techniques.
AB  - STUDY DESIGN: Eight human cadaveric lumbosacral spines were biomechanically and
      kinematically tested in torsion and compression-flexion. They were retested after
      simulated posterolateral fusion, anterior lumbar interbody fusion, and
      circumferential fusion. OBJECTIVES: To analyze stiffness and motion in the
      anterior and posterior columns of the index and contiguous spinal motion units of
      anterior, posterolateral, and circumferential fusions. SUMMARY OF BACKGROUND
      DATA: Previous biomechanical studies have not incorporated analysis of motion
      with six degrees of freedom, consideration of contiguous levels, and comparisons
      of anterior and posterior column motion. METHODS: Eight human cadaveric
      lumbosacral spines were biomechanically tested in compression-flexion and torsion
      using an advanced biplanar radiography technique. Each specimen underwent either
      a simulated posterolateral fusion or anterior fusion followed by a
      circumferential fusion. Motion and stiffness at the level of the fusion and at
      contiguous levels were analyzed independently in the anterior and posterior
      columns of the spine. RESULTS: At the level of fusion, the simulated
      posterolateral and anterior fusions prevented more motion in torsion compared
      with compression-flexion. With all specimens, it was shown that circumferential
      fusions were stiffer than the intact specimen. Our comparison of motion in the
      anterior and posterior columns found no significant differences within the
      columns of a single vertebral motion segment. Compared with posterolateral
      fusions, anterior fusions were found to have the greatest effect in increasing
      motion at contiguous levels. The effect of circumferential fusions on adjacent
      level kinematics was not significantly greater than that of anterior fusions.
      CONCLUSION: There are major biomechanical differences between different fusion
      techniques. This information should be considered in patients undergoing lumbar
      spinal fusion.

PMID- 8882690
TI  - Anatomic consideration of C2 pedicle screw placement.
AB  - STUDY DESIGN: This anatomic study tested placement of C2 pedicle screws using
      cadaver specimens. OBJECTIVES: To further assess the safety of transpedicular
      screw placement in the axis by comparing two surgical techniques. SUMMARY OF
      BACKGROUND DATA: Transpedicular screw fixation of traumatic spondylolisthesis of
      the axis has been described in the literature. Recently, anatomic studies and
      clinical applications of transpedicular screw fixation for traumatic lesions of
      middle and lower cervical spine have been described. No previous study assessing
      the safety of C2 pedicle screw placement is available. METHODS: Sixteen embalmed
      cadaveric specimens were used for this study. In the first eight specimens
      (Method A), the point of entry for screw placement was chosen to be about 5 mm
      inferior to the superior border of C2 lamina and 7 mm lateral to the lateral
      border of the spinal canal. The screw direction was chosen to be about 30 degrees
      medial to the sagittal plane and 20 degrees cephalad to the transverse plane. A
      3.5-mm cortical screw of appropriate length, determined with depth gauge, was
      placed bilaterally into the C2 pedicle. In the next eight specimens (Method B),
      the direction of the drill bit was guided directly by the medial and superior
      aspect of the individual C2 pedicle. Gross dissection was done to view violation
      of dura, nerve roots, vertebral artery, and penetration of medial, lateral,
      superior, and inferior cortex of the C2 pedicle. Radiographs and computed
      tomography scans were obtained to evaluate screw placement in the C2 pedicle.
      RESULTS: In Method A, four screws had lateral violations into the vertebral
      artery. In Method B, only two cases of minimal penetration of pedicle cortex were
      found. No medial, superior, or inferior violation of the pedicle cortex was found
      in the present study. CONCLUSIONS: The present anatomic study suggests that
      transpedicular screw fixation may be performed safely in the C2 pedicle by using
      the second technique. Using the first technique is not safe.

PMID- 8882689
TI  - Cervical interbody xenograft with plate fixation: evaluation of fusion after 7
      years of use in post-traumatic discoligamentous instability.
AB  - STUDY DESIGN: This retrospective study analyzed clinical and radiologic follow-up
      evaluations of cervical arthrodesis where interbody xenograft combined with
      internal fixation was used for management of post-traumatic discoligamentous
      instability. OBJECTIVES: To report results of use of xenograft to avoid the
      various disadvantages linked to the use of autologous or allogenous bone graft.
      SUMMARY OF BACKGROUND DATA: Ligamentous instability of the cervical spine is
      unlikely to heal in a high proportion of cases, and surgical arthrodesis is
      usually indicated. Anterior arthrodesis has proved to be a safe procedure, but
      many problems are associated with the use of autograft or allograft. Given the
      great number of xenograft procedures, there are relatively few reports in the
      literature. METHODS: A retrospective study analyzed a consecutive series of 52
      patients presenting with post-traumatic discoligamentous instability of the
      cervical spine in which cervical interbody xenografts with plate fixations were
      done. Follow-up clinical evaluation for neck pain and radiologic evaluation for
      arthrodesis stability and xenograft fusion at various points in time were done.
      RESULTS: The long-term results in 41 patients were satisfactory: no infectious
      complications, extrusion, fracture, loss of height, or resorption of the graft.
      Seventy-five percent fusion was seen before 9 months after surgery, and 100%
      fusion was seen 3-18 months after surgery (average, 7.4 months). CONCLUSIONS:
      Interbody xenograft combined with a rigid plate fixation avoids the problems
      linked to autologous or allogenous bone graft and gives a safe and solid
      interbody fusion when arthrodesis is required in ligamentous instability of the
      cervical spine.

PMID- 8882691
TI  - Evaluation of cervical posterior lateral mass screw placement by oblique
      radiographs.
AB  - STUDY DESIGN: The present study analyzed the two-dimensional representation of
      cervical lateral mass screws by oblique radiographs compared with cadaveric
      placement. This was accomplished by posterior and lateral cervical dissection of
      the lateral masses and intervertebral foramina, keeping the emerging nerve roots
      intact. The intervertebral foramina were divided into two zones for the study.
      OBJECTIVES: To identify and describe the value of oblique radiographs in
      evaluating posterior lateral mass screw placement in the cervical spine. SUMMARY
      OF BACKGROUND DATA: Posterior plate-screw fixation is an effective method of
      stabilizing the traumatized cervical spine. Because of the surrounding anatomy,
      precise placement of screws must be attained to avoid iatrogenic injury to the
      nerve roots, and incorrectly placed screws must be identified quickly to minimize
      the neurologic complication. No previous radiologic study regarding evaluation of
      the lateral mass screw placement has been reported. METHODS: Six cervical spines
      were removed from embalmed cadavers. Posterior and lateral removal of soft tissue
      ensued until the lateral masses and spinal nerves were clearly and completely
      exposed. Two specimens and 20 screws were used for each of the following methods:
      Roy-Camille, zone 1 placement, and zone 2 placement. Zone 1 was defined as the
      area between pedicles of adjacent vertebrae. Zone 2 was defined as the area
      between transverse processes of adjacent vertebrae. Forty-five degrees oblique
      left and right, anteroposterior, and lateral radiographs were taken. RESULTS: All
      screws placed by the Roy-Camille technique and 19 of 20 screws intentionally
      placed in zone 1 were represented accurately by oblique radiographs. Nineteen of
      20 screws placed in zone 1 were well appreciated in the foramen in oblique view.
      However, 13 of 20 screws placed in zone 2 and approximating the nerve root were
      inaccurately represented or ambiguous in oblique radiographs. CONCLUSIONS:
      Oblique radiographs are valuable to view the relationship between screw placement
      and foramina. Screws crossing the line connecting the posterior borders of the
      intervertebral foramina and appearing in the pedicle actually exit the bone and
      may risk damaging the nerve root.

PMID- 8882692
TI  - Back pain during pregnancy: a prospective study.
AB  - STUDY DESIGN: A longitudinal, prospective, observational, cohort study.
      OBJECTIVES: To describe the natural history of back pain occurring during
      pregnancy and immediately after delivery. SUMMARY OF BACKGROUND DATA: Back pain
      during pregnancy is a frequent clinical problem even during the early stages of
      pregnancy. The cause is unclear. METHODS: A cohort of 200 consecutive women
      attending an antenatal clinic were followed throughout pregnancy with repeated
      measurements of back pain and possible determinants by questionnaires and
      physical examinations. RESULTS: Seventy-six percent reported back pain at some
      time during pregnancy. Sixty-one percent reported onset during the present
      pregnancy. In this group, the prevalence rate increased to 48% until the 24th
      week and then remained stable and declined to 9.4% after delivery. The reported
      pain intensity increased by pain duration. The pain score correlated closely to
      self-rated disability and days of sickness benefit. CONCLUSIONS: Back pain during
      pregnancy is a common complaint. The 30% with the highest pain score reported
      great difficulties with normal activities. The back pain started early in
      pregnancy and increased over time. Young women had more pain than older women.
      Back pain starting during pregnancy may be a special entity and may have another
      origin than back pain not related to pregnancy.

PMID- 8882693
TI  - Are occupational drivers at an increased risk for developing musculoskeletal
      disorders?
AB  - STUDY DESIGN: This study analyzed the role of exposure to driving and other
      covariates in reports of back, neck, and shoulder pain and resultant disability.
      Cohorts in Sweden and the United States were compared. OBJECTIVES: To establish
      the effect of mechanical and psychosocial factors in reporting back, neck, and
      shoulder pain and work loss. SUMMARY OF BACKGROUND DATA: There are numerous
      reports of a positive relationship between back pain and driving. However,
      exposure data are minimal. The influence of job satisfaction has not been
      assessed. METHODS: The physical factors affecting reports of back, neck, and
      shoulder pain were investigated in a two-country cohort study of bus and truck
      drivers and sedentary workers. Vibration exposure was obtained by directly
      measuring the vibration imposed on the driver during a typical work day. Lifting
      exposure was attained by questionnaire. Cumulative exposure was computed based on
      work history. Musculoskeletal health information was based on a modified nordic
      questionnaire, and other questionnaires recorded the physical and psychosocial
      aspects of the work environment. RESULTS: Of the sample, 50% reported low back
      pain, with no difference between countries. The highest risk factors (odds
      ratios) for back and neck pain were long-term vibration exposure, heavy lifting,
      and frequent lifting. A combination of long-term vibration exposure and frequent
      lifting carried the highest risk of low back pain. Work loss from low back pain
      was influenced by perceived job stress. CONCLUSIONS: Vibration (resulting from
      driving) and lifting cause back, neck, and shoulder pain, whereas inability to
      work seems affected by stress at work.

PMID- 8882694
TI  - Thoracic volume changes in scoliosis surgery.
AB  - STUDY DESIGN: Eighteen patients with adolescent idiopathic scoliosis treated with
      ISOLA instrumentation and 13 treated with Cotrel-Dubousset instrumentation were
      studied before and after surgery with computed tomography scans. OBJECTIVES: To
      analyze and compare the immediate change in chest volume of patients treated with
      the derotation method of Cotrel-Dubousset versus the sublaminar wire
      translational technique of ISOLA. SUMMARY OF BACKGROUND DATA: Previous literature
      suggests a small but variable improvement in pulmonary function with the use of
      Harrington instrumentation when treating adolescent idiopathic scoliosis. The
      effect of modern instrumentation techniques on chest volume and ultimately
      pulmonary function has not been determined. METHODS: An axial computed tomography
      slice was made through each vertebral body from T3 to T10. Using a technique of
      spine curve measurements, the cross-sectional area at each level was computed,
      and from the height measured, the volume of the thoracic cage was computed.
      RESULTS: Single thoracic curves (King-Moe Type III) managed with ISOLA sublaminar
      instrumentation showed a statistically significant increase in chest volume when
      compared with other curve types and when compared with all curves managed with
      Cotrel-Dubousset. Seventeen of 18 patients treated with ISOLA instrumentation
      gained chest volume, whereas half of those treated with Cotrel-Dubousset actually
      lost volume. CONCLUSIONS: ISOLA instrumentation and sublaminar wiring appears to
      increase the chest volume in patients with adolescent idiopathic scoliosis. Its
      clinical significance remains to be determined.

PMID- 8882695
TI  - Inappropriate secretion of antidiuretic hormone in postoperative scoliosis
      patients: the role of fluid management.
AB  - STUDY DESIGN: The present study examined the hypothesis that hypotonic saline
      therapy before surgery was a major factor in the development of the syndrome of
      inappropriate antidiuretic hormone secretion. OBJECTIVES: The influence of fluid
      therapy and its relationship to the syndrome of inappropriate antidiuretic
      hormone secretion was studied by measuring patient electrolyte and osmolar
      responses at given times after surgery. SUMMARY OF BACKGROUND DATA: Mild renal
      dysfunction and increased plasma antidiuretic hormone occurs after surgery.
      Occurrence of the syndrome of inappropriate secretion of antidiuretic hormone
      after spine surgery is rare. The development of the syndrome of inappropriate
      secretion hormone after surgery may be related to hypotonic fluid replacement
      during and after surgery. METHODS: Twelve patients undergoing surgery for
      correction of idiopathic scoliosis were assigned randomly to two groups. The
      control group (five patients) was given isotonic saline, and the trial group
      (seven patients) was given hypotonic saline. RESULTS: The trial group developed
      syndrome of inappropriate antidiuretic hormone secretion with a significant
      decrease in serum sodium and osmolarity. The control group did not develop
      syndrome of inappropriate antidiuretic hormone secretion. CONCLUSIONS: Hypotonic
      saline therapy predisposes to the development of syndrome of inappropriate
      antidiuretic hormone secretion, whereas isotonic saline protects patients from
      syndrome of inappropriate antidiuretic hormone secretion when undergoing surgery
      for scoliosis.

PMID- 8882696
TI  - Surgical treatment of severe L5-S1 spondylolisthesis in children and adolescents.
      Results of intraoperative reduction, posterior interbody fusion, and segmental
      pedicle fixation.
AB  - STUDY DESIGN: A retrospective study was done in 12 teenagers with severe L5-S1
      spondylolisthesis surgically treated with a single-stage posterior procedure for
      reduction, posterior interbody fusion, and segmental instrumentation. OBJECTIVE:
      To evaluate the effectiveness and reliability of intraoperative reduction and
      posterior interbody fusion in severe lumbosacral spondylolisthesis in children.
      SUMMARY OF BACKGROUND DATA: Twelve young patients (age, 13-18 years; mean = 16 +/
      1.5) with severe L5-S1 spondylolisthesis (slip, 59%-85%; mean = 70.4 +/- 8.8%)
      were available for follow-up evaluation (6-24 months after surgery). All
      presented with serious preoperative clinical signs (tight hamstrings, waddling
      gait, lumbosacral pain, radiated leg pain). METHODS: The patients underwent
      surgery using a single posterior surgical procedure. After removal of the
      loosened arch and complete discectomy, a temporary device placed bilaterally
      between L1 and the sacral wings was used to achieve reduction by distraction.
      This was followed by a posterior interbody strut graft and pedicle segmental
      fixation. No postoperative casting was used. Clinical examination was done, and
      radiographic measurements were taken after surgery and at follow-up evaluation.
      Patients were evaluated for fusion rate, stability of reduction, clinical
      outcome, and possible complications. RESULTS: All patients underwent solid fusion
      without loss of reduction. No intraoperative or postoperative complications were
      observed. Mean correction of the initial slipping was 79.5 +/- 7% of the initial
      deformity. No clinical signs were present at follow-up evaluation. CONCLUSIONS:
      Intraoperative distraction appears to be truly effective in reducing severe
      lumbosacral olyshtesis in children. Posterior interbody fusion (and eventual
      sacral dome osteotomy) successfully combines the goals of solid fusion with the
      requirements of root decompression. No neurologic problems were seen as a
      consequence of distraction. The solidity of the posterior segmental pedicle
      instrumentation combined with the anterior strut graft eliminate the need for
      postoperative casting.

PMID- 8882697
TI  - Anterior instrumentation of the spine in thoracic and thoracolumbar fractures:
      the single rod versus the double rod Slot-Zielke device.
AB  - STUDY DESIGN: This retrospective study analyzed the clinical and radiologic
      results of two groups of patients with unstable burst fractures of the
      thoracolumbar spine treated with anterior decompression, reduction of the
      kyphotic deformity, and stabilization by grafting and instrumentation. OBJECTIVE:
      To compare the results regarding loss of correction of two groups of patients
      treated with two different configurations of the same instrumentation, the so
      called "Slot-Zielke" device. SUMMARY OF BACKGROUND DATA: Decompression of burst
      fractures and reduction of kyphotic deformity are facilitated by the anterior
      approach to the spine. The maintenance of reduction depends on the strength of
      the grafting material and on the rigidity of the internal fixation. METHOD: Forty
      consecutive patients with spine fractures underwent surgery for anterior
      decompression, reduction of kyphotic deformity, and stabilization by grafting and
      instrumentation. The first group of 25 patients (Group A) received a single rod
      "Slot-Zielke" device as an implant. The second group of 15 patients (Group B)
      received a double rod "Slot-Zielke" device. Before and at least 2 years after
      surgery, the kyphotic angle between the vertebrae above and below the fracture
      was measured. RESULTS: The clinical results at follow-up evaluation were similar
      between the groups. In Group A, 60% of the cases had a loss of correction of 5
      degrees or more (least square mean, 5.64 degrees; range, 0-23 degrees). In Group
      B, the loss of correction in all cases was less than 5 degrees (least square
      mean, 1.60 degrees; range, 0-4 degrees). The difference between the average of
      both groups was highly significant (P = 0.014). CONCLUSION: The double rod
      instrumentation performs significantly better regarding loss of correction
      compared with the single rod instrumentation.

PMID- 8882698
TI  - The North American spine society lumbar spine outcome assessment Instrument:
      reliability and validity tests.
AB  - STUDY DESIGN: A cross-sectional study of a convenience sample of lumbar spine
      patients, with a subsample followed for retest reliability. OBJECTIVES: To assess
      the instrument's reliability, validity, and acceptability to patients. SUMMARY OF
      BACKGROUND DATA: Patients with eight diagnoses, four before surgery and four
      after surgery, were recruited from six orthopedic practices to test the
      questionnaire. METHODS: One hundred sixty-seven patients were approached through
      the physician's office, yielding 136 usable questionnaires (84%) and 24-hour
      retests on 64 patients. RESULTS: The questionnaire took about 20 minutes to
      administer and was acceptable to patients. The lumbar spine pain and disability
      and neurogenic symptoms subscales discriminated among patient groups as
      hypothesized and showed significantly better scores for patients independently
      judged successful by their physicians after surgery. Test-retest reliability and
      internal reliability were high (range, 0.85-0.97). Sample sizes of 20-37 would be
      needed to detect a 20% difference between two groups (alpha, 0.05; beta, 0.20).
      CONCLUSIONS: The questionnaire should be considered for monitoring of individual
      patient's progress in treatment and for clinical trials.

PMID- 8882699
TI  - Dose distribution at radiographic examination of the spine in pediatric
      radiology.
AB  - STUDY DESIGN: The radiation dose distribution at radiographic examinations of the
      lumbar spine and the thoracic spine and at examinations for scoliosis has been
      investigated in pediatric patients. OBJECTIVES: To derive the conversion factors
      between the entrance surface dose and the mean absorbed dose to the most
      radiation-sensitive organs, and to determine the dose level and its variation for
      patients. SUMMARY OF BACKGROUND DATA: Fifty-five patients participated in the
      survey. Mathematically describable phantoms were used to simulate the body of
      children of various ages. METHODS: Relative absorbed dose in the body was
      determined with measurements. The entrance surface dose and the dose-area product
      were measured for a number of patients. The effective dose and its variation
      between patients were estimated. RESULTS: The mean entrance surface doses were
      highest for the lumbar spine examinations (2.6 mGy, anteroposterior projection;
      6.7 mGy, lateral projection). The female gonads received the highest dose. The
      mean entrance surface doses for the thoracic spine examinations were 2.1 mGy for
      the frontal view and 6.1 mGy for the lateral view. The breasts, thyroid, lungs,
      and esophagus received the highest absorbed dose. Mean effective dose for one
      frontal and one lateral view was slightly higher for lumbar spine examinations
      than for thoracic spine examinations. An optimized scoliosis examination gives a
      much lower effective dose, about 0.05 mSv (frontal view). If an additional
      exposure determining the "skeletal age" is performed, the effective dose rises
      with 0.12 mSv. CONCLUSIONS: Thoracic spine and lumbar spine examinations lead to
      relatively high-absorbed doses to radiation-sensitive organs. Because the
      scoliosis investigation is repeated several times, the total effective dose could
      be considerable.

PMID- 8882700
TI  - Atlantoaxial instability in Lesch-Nyhan syndrome.
AB  - STUDY DESIGN: A clinical case report of two brothers with Lesch-Nyhan syndrome
      found to have atlantoaxial instability is reported. OBJECTIVES: To report the
      clinical and radiologic findings and the operative outcome in these patients.
      SUMMARY OF BACKGROUND DATA: Both patients had biochemically proven Lesch-Nyhan
      syndrome. No previous cases of cervical instability have been reported in this
      group of patients. METHODS: The first patient presented with neck pain and
      progressive quadriplegia. Radiology including computed tomography scanning showed
      fracture of the tip of the odontoid and forward subluxation of the atlas. He was
      treated with a C1-C2 Gallie fusion. The second patient (his brother) was found to
      have similar radiologic findings but had not developed quadriplegia. He has not
      required surgery. RESULTS: At surgery, attempted correction of the subluxation
      produced severe bradycardia. An in situ fusion was performed that relieved the
      patient's neck pain. The child's neurologic status has remained the same during a
      16-month follow-up period, despite failure of the posterior wire fixation 12
      months after surgery. CONCLUSIONS: Patients with Lesch-Nyhan syndrome may develop
      atlantoaxial instability with subsequent neck pain and quadriplegia that may be
      masked by their underlying disease. Posterior fusion produced symptomatic relief
      but no improvement in neurologic status in our patient. Posterior fusion probably
      should be augmented by rigid cervical immobilization until fusion is confirmed in
      this type of patient.

PMID- 8882701
TI  - Meningitis complicating spinal surgery.
AB  - STUDY DESIGN: A retrospective review of all cases of bacterial meningitis after
      spinal surgery. OBJECTIVES: To identify the usual clinical and laboratory
      features, and to determine the frequency of this complication. SUMMARY OF
      BACKGROUND DATA: Meningitis has been recognized as a rare complication of spinal
      surgery, but no series of cases has been reported previously, and there are no
      published estimates of its frequency. METHODS: A retrospective review of the
      medical records of all cases of bacterial meningitis after spinal surgery in
      Auckland over a 3-year period was done. RESULTS: Four cases were identified after
      2180 operations, an incidence of 0.18%. All four patients survived. CONCLUSIONS:
      This is a rare complication from which a good outcome is possible with early
      diagnosis and prompt management.

PMID- 8882702
TI  - Intramedullary tuberculous abscess: a case report.
AB  - STUDY DESIGN: This case report shows an intramedullary thoracic spinal cord
      abscess secondary to Mycobacterium tuberculosis in a 7-year-old boy with chronic
      progressive paraparesis and hypesthesia below T10. OBJECTIVES: The treatment of
      this patient involved drainage of pus followed by appropriate chemotherapy.
      SUMMARY OF BACKGROUND DATA: Abscess and tuberculomas of the spinal cord are rare
      entities. They are indistinguishable from neoplasms. The possibility of
      tubercular abscess or granuloma should be kept in mind when an intraspinal mass
      is found, provided that the clinical history is unusual for tumor. METHODS: A
      left T7-T8 hemilaminectomy was performed. A quantity of pus was drained through a
      small myelotomy. A small specimen was taken, and antituberculosis treatment was
      given after surgery. RESULTS: Excellent clinical outcome was obtained with a
      combination of medical and surgical management. CONCLUSION: The treatment of
      intramedullary abscess consists of surgical evacuation of the pus. Appropriate
      treatment offers a favorable prognosis even in cases with severe deficits.

PMID- 8882703
TI  - Congenital spine deformity, congenital stenosis, diastematomyelia, and tight
      filum terminale in a workmen's compensation patient: a case report.
AB  - STUDY DESIGN: This case report concerns a patient injured at work who was denied
      adequate evaluation and treatment by a Workman's Compensation Commission,
      resulting in nearly complete paraplegia. OBJECTIVES: For a patient with a
      congenital spine deformity, a diastematomyelia, a tight filum terminale, and a
      congenital stenosis, denial of magnetic resonance imaging evaluation and
      appropriate surgery cannot be justified. SUMMARY OF BACKGROUND DATA: This 35-year
      old man injured his knee and back in a fall at work but was able to work for 1
      week. Progressive neurologic deterioration was documented, but magnetic resonance
      imaging evaluation was denied. When it finally obtained and the lesion
      identified, appropriate neurosurgery was denied. METHODS: When seen by the
      authors more than 3 years after his injury, he had a nearly complete paraplegia.
      Despite neurosurgical decompression and spine stabilization, no significant
      recovery occurred. RESULTS: A nearly complete paraplegia resulted from this
      combination of lesions coupled with intolerable delay in diagnosis and therapy,
      both the result of "foot-dragging" by a Workmen's Compensation Commission.
      CONCLUSIONS: In an effort to be "cost-conscious" and to avoid "unnecessary low
      back surgery," a Workmen's Compensation Commission has caused a patient to become
      paraplegic. Such management is neither cost-effective nor of adequate quality.

PMID- 8882704
TI  - Far lateral disc herniations.

PMID- 8882705
TI  - Prevalence and clinical features of internal disk disruption in patients with
      chronic low back pain.

PMID- 8882707
TI  - Homologous recognition by RecA protein using non-equivalent three DNA-strand
      binding sites.
AB  - A key step in homologous recombination is the formation of a heteroduplex joint
      between double-stranded DNA and single-stranded DNA by the homologous pairing and
      strand-exchange, and this step is also important in recombinational repair of
      damaged DNA in various organisms. The homologous pairing and the strand-exchange
      are promoted in vivo and in vitro by RecA protein of Escherichia coli or its
      homologues of bacteria, virus, and lower and higher eukaryotes. A central
      question on the mechanism of homologous recombination is how RecA protein (and
      its homologues) recognizes homologous sequences between single-stranded DNA and
      double-stranded DNA. Recent studies suggest that RecA protein promotes homologous
      recognition between these DNA molecules by the formation of a transient and
      additional pairing of identical sequences via non-Watson-Crick interactions to
      the Watson-Crick-type duplex DNA, and that RecA protein uses three non-equivalent
      DNA-strand-binding sites in this reaction.

PMID- 8882706
TI  - Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis.
AB  - Activated gelatinase A is reportedly associated with tumor spread. We identified
      novel matrix metalloproteinases that localize on the cell surface and mediate the
      activation of progelatinase A. Thus, these progelatinase A activators were named
      membrane-type matrix metalloproteinase-1 and -2 (MT-MMP-1 and -2, respectively).
      MT-MMP-1 is overexpressed in malignant tumor tissues, including lung and stomach
      carcinomas that contain activated gelatinase A. This suggests that MT-MMP-1 is
      associated with the activation of progelatinase A in these tumor tissues. The
      expression of MT-MMP-1 also induced binding of gelatinase A to the cell surface
      by functioning as a receptor. The cell surface localization of proteinases has
      advantages over pericellular proteolysis. MT-MMP-1 and its family may play a
      central role in the cell surface localization and activation of progelatinase A
      and via this mechanism, tumor cell use exogenous progelatinase A to mediate the
      proteolysis associated with invasion and metastasis.

PMID- 8882708
TI  - Crystallization and preliminary X-ray diffraction study of recombinant human
      eukaryotic initiation factor-4E.
AB  - Recombinant human eukaryotic initiation factor-4E (eIF-4E), purified by m7GTP
      Sepharose 4B affinity chromatography, was used for crystallization. After
      concentration of the eIF-4E protein (7 mg/ml), the solution was subjected to
      crystallization by the hanging-drop method. Transparent needle crystals complexed
      with m7GTP were obtained from 50 mM 2-(N-morpholino)ethanesulfonic acid-KOH
      buffer (pH 6.5) containing 25% (w/v) polyethylene glycol 6000 and 0.2 M
      (NH4)2SO4. The crystals belong to tetragonal space group P4(1) or P4(3), of Z =
      4, with unit-cell dimensions of a = 89.26, b = 89.26, and c = 38.51 angstrum, and
      diffract beyond 2.1 angstrum resolution. The Vm value was calculated to be 3.07
      angstrum 3/Da, which indicates a solvent content of 59.9%.

PMID- 8882709
TI  - Structure determination of an immunopotentiator peptide, cinnamycin, complexed
      with lysophosphatidylethanolamine by 1H-NMR1.
AB  - The three-dimensional structure of a complex of cinnamycin, a 19-amino acid
      residue immunopotentiator peptide, and lysophosphatidylethanolamine was
      determined by 1H-NMR. The complex was cylindrical in shape, 11 A in diameter and
      26 A in length, excluding the acyl chain of the phospholipid. The peptide had a
      hydrophobic pocket surrounded by residues Phe-7 through Ala(S)-14 to bind to the
      head group of the ligand. Fitting of the head group to the hydrophobic pocket was
      so good that other than a glycerophosphoethanolamine head group would be unable
      to fit the pocket. The goodness of the fitting is compatible with the strict
      specificity of ligand binding of the peptide.

PMID- 8882710
TI  - Structure of mouse interferon stimulated gene factor 3 gamma (ISGF3 gamma/p48)
      cDNA and chromosomal localization of the gene.
AB  - Interferon stimulated gene factor 3 (ISGF3) is a trimeric transcription factor
      activated on treatment of cells with interferon-alpha and beta (type I IFNs).
      Upon stimulation, the regulatory subunits, p84/91 and p113, present in the
      cytoplasm are phosphorylated at specific tyrosine residues and assemble with the
      DNA binding subunit, ISGF3 gamma, into the active ISGF3 in the nucleus. Thus,
      ISGF3 plays a primary role in the transmission of a signal from the cell surface
      to the nucleus. In this report, we describe the cloning of a mouse cDNA encoding
      a polypeptide homologous to human ISGF3 gamma. Comparison of the deduced amino
      acid sequences revealed the middle region was significantly different between
      mouse and man. The mouse cDNA was shown to encode a functional ISGF3 subunit by
      means of an in vitro reconstitution assay. Furthermore, the locus of the ISGF3
      gamma gene, designated as Isgf3g, was mapped to distal mouse chromosome 14 by
      linkage analysis using an intersubspecific backcross typing panel.

PMID- 8882711
TI  - Characterization of the human full-length PTK7 cDNA encoding a receptor protein
      tyrosine kinase-like molecule closely related to chick KLG.
AB  - A 220-bp fragment of PTK7 cDNA was previously cloned from normal human melanocyte
      RNAs by means of the reverse transcription-polymerase chain reaction [Lee, S.-T.,
      Strunk, K.M., and Spritz, R.A. (1993) Oncogene 8, 3403-3410]. We now report the
      cloning of the human full-length PTK7 cDNA and its characterization. The 1,070
      amino acid PTK7 polypeptide deduced from the cDNA sequence constitutes receptor
      protein tyrosine kinase (RPTK), but has several unusual residues in some of the
      highly conserved tyrosine kinase motifs. PTK7 mRNA was expressed at the highest
      level in a human erythroleukemia cell line among tested samples, and at
      relatively high levels in liver, lung, pancreas, kidney, placenta, and
      melanocytes. Human PTK7 is 72% identical to chick KLG, suggesting that PTK7 is
      homologous or possibly orthologous to chick KLG, and that these represent a new
      subfamily of RPTKs.

PMID- 8882712
TI  - Age-related changes in lipid secretion of perfused livers from male Wistar rats
      donors.
AB  - Male Wistar rats show typical age-related variations in the distribution of high
      density lipoprotein subfractions that include an increase in HDL1 and a decrease
      in HDL2 proportion. The role of liver in these variations was evaluated by
      studying the lipoprotein and bile secretions from perfused livers of 14 +/- 1 and
      3.5 +/- 0.5 month old Wistar rats (adult and young animals, respectively). The
      lipid content of lipoproteins secreted from adult livers was higher in HDL2
      fraction and lower in VLDL fraction. The lipid output did not show significant
      age-related variations in the case of HDL1 fraction. However, the lipoproteins
      secreted from adult livers contained a higher proportion of phospholipids, and a
      lower proportion of triacylglycerols in comparison with lipoproteins secreted by
      young livers. Therefore, the molar ratio of core to surface lipids was lower in
      lipoproteins secreted by adult livers. Adult livers showed a reduction in bile
      flow by about 37% with a significantly higher phospholipid secretion. These
      findings suggest that both the hepatic metabolism of glycerophospholipids and
      their repartition between plasma and bile compartments are affected by aging
      process. In conclusion, present data show that the age-related increase in plasma
      HDL1 proportion, previously observed in this rat strain in vivo, are not due to a
      higher liver secretion of these particles. Conversely, liver appears to have a
      major role in the age-related VLDL increase and in the variations of phospholipid
      lipoprotein secretion.

PMID- 8882713
TI  - A detoxication route for acetaldehyde: metabolism of diacetyl, acetoin, and 2,3
      butanediol in liver homogenate and perfused liver of rats.
AB  - The metabolism of diacetyl (2,3-butanedione), acetoin (3-hydroxy-2-butanone), and
      2,3-butanediol, which are metabolites of acetaldehyde was quantitatively
      investigated using rat liver homogenate, liver perfusion, and in vivo
      experiments. Diacetyl and acetoin were reduced to 2,3-butanediol in these
      experiments, but acetoin and 2,3-butanediol were scarcely oxidized to diacetyl,
      indicating that the reduction reaction to 2,3-butanediol from diacetyl occurs
      actively in rat liver. The formation of acetoin from diacetyl required either
      NADH or NADPH as a reductant, while the reduction of acetoin to 2,3-butanediol
      required NADH. Acetoin and 2,3-butanediol were more readily accumulated than
      diacetyl in brain tissue.

PMID- 8882714
TI  - A method for screening antisense oligodeoxyribonucleotides effective for mRNA
      translation-arrest.
AB  - A transcription and translation coupled reticulocyte lysate system was
      established for rapid screening of antisense oligodeoxyribonucleotides (ODNs) to
      determine which are most effective for mRNA translation-arrest. A plasmid
      containing the target cDNA under the control of the T7 (or SP6) promoter was
      added to the lysate system in the presence of the T7 (or SP6) RNA polymerase,
      RNase H, and the antisense ODN under test. Transcription and translation were
      accomplished in a one-tube reaction. Translation-arrest caused by antisense ODN
      was evaluated in terms of the amounts of de novo-synthesized, [35S]-methionine or
      [35S]cysteine labeled target protein measured by gel electrophoresis and
      autoradiography. The properties of this system and optimal reaction conditions
      for use in antisense ODN screening were determined. Our method is simpler and
      more rapid than other in vitro screening methods.

PMID- 8882715
TI  - Characterization of NADPH-dependent ubiquinone reductase activity in rat liver
      cytosol: effect of various factors on ubiquinone-reducing activity and
      discrimination from other quinone reductases.
AB  - Cytosolic NADPH-dependent ubiquinone reductase (NADPH-UQ reductase) accounted for
      about 68% of the total ubiquinone (UQ) reductase activity in rat liver homogenate
      [Takahashi, T. et al. (1995) Biochem. J. 309, 883-890]. We investigated the
      effects of various factors on this enzyme activity in rat liver cytosol with the
      aim of elucidating its physiological roles. The NADPH-UQ reductase in rat liver
      cytosol catalyzed the reduction of UQ to UQH2 with concomitant oxidation of
      equimolar NADPH. The optimal pH was around 7.4, and the optimal temperatures were
      about 28 degrees C for NADH and about 37 degrees C for NADPH. NADH, deamino NADH,
      and deamino NADPH were much less active hydrogen donors than NADPH, whereas
      reduced nicotinamide mononucleotide, ascorbate, erythorbate, reduced glutathione,
      and cysteine were inactive. As the hydrogen acceptor, UQ-9 had the highest
      Vmax/Km among the long-chain UQ homologues tested. FAD and FMN stimulated the
      activity. Anionic detergents, Mg2+ and Sr2+ also enhanced the activity. Rotenone,
      malonic acid, antimycin A, and KCN, which inhibit mitochondrial and microsomal
      electron transfer enzymes, superoxide dismutase, and acetylated cytochrome c had
      no effect on the NADPH-UQ reductase activity. These results indicated that the
      NADPH-UQ reductase in rat liver cytosol is a flavoprotein that reduces UQ-10 by a
      two-electron reduction mechanism and is distinguishable from known microsomal and
      mitochondrial enzymes, as well as DT-diaphorase [EC 1.6.99.2].

PMID- 8882716
TI  - Change in the expression of C-type natriuretic peptide and its receptor, B-type
      natriuretic peptide receptor, during dedifferentiation of chondrocytes into
      fibroblast-like cells.
AB  - Chondrocytes derived from rat xiphoid cartilage dedifferentiated into fibroblast
      like cells as the number of passages of the cells in culture increased. During in
      vitro dedifferentiation the growth of the cells was markedly suppressed. We had
      proposed previously that C-type natriuretic peptide (CNP) might be a potent
      antimitogenic factor for chondrocytes, and TGF-beta 1 induced a marked increase
      in CNP secretion of chondrocytes. Therefore, we investigated the expression of
      CNP, B-type natriuretic peptide receptor (NPR-B or GC-B), and TGF-beta 1 in this
      process. Radioimmunoassay and RNase protection analyses revealed passage
      associated increase in CNP-like immunoreactivity and in levels of NPR-B mRNA,
      respectively. Northern blot analyses showed that the level of TGF-beta 1 mRNA
      decreased with increasing passage number. These results suggest that the
      expression of CNP and NPR-B might be involved in in vitro dedifferentiation of
      chondrocytes and TGF-beta 1 does not affect the increasing level of CNP during in
      vitro dedifferentiation.

PMID- 8882717
TI  - Purification and characterization of active fragment of Ca2+/calmodulin-dependent
      protein kinase II from the post-synaptic density in the rat forebrain.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) of the post-synaptic
      density (PSD) was solubilized and activated 4- to 5-fold by limited alpha
      chymotrypsin digestion with prior autophosphorylation of the kinase. The enzyme
      was also activated by trypsin and mu-calpain, a Ca(2+)-dependent protease. The
      active catalytic fragment was purified to homogeneity using gel filtration and
      ion exchange chromatography. The purified active fragment was completely
      Ca2+/calmodulin-independent and exists as a monomer. Kinetic studies with the
      purified fragment revealed similar Km values for ATP and synthetic peptide
      substrate, and an about 8-fold increment in Vmax, compared with native PSD CaM
      kinase II.

PMID- 8882718
TI  - Uncoupling mechanism of glycoside antibiotic aculeximycin in isolated rat-liver
      mitochondria.
AB  - Effects of basic glycoside antibiotic aculeximycin (ACM) on the oxidative
      phosphorylation of rat-liver mitochondria were examined. ACM was shown to be a
      potent uncoupler of the oxidative phosphorylation. To cause the same extent of
      respiration release, higher concentration of ACM was required in phosphate (Pi)
      free medium than in Pi medium. During the uncoupling caused by ACM in Pi medium,
      large amplitude swelling and oxidation of intramitochondrial NAD(P)H occurred,
      indicating that ACM remarkably enhances permeability of the inner mitochondrial
      membrane. The Pi uptake via Pi/H+ symporter was shown to play an important, but
      not essential, role in the uncoupling by ACM, indicating the increase in membrane
      permeability is mostly due to acceleration of Pi/H+ influx through Pi/H+
      symporter activated by ACM. ACM is the first naturally occurring antibiotic, to
      our knowledge, which activates Pi/H+ symporter. However, since the inhibition of
      Pi/H+ symporter by N-ethylmaleimide did not completely abolish the uncoupling
      activity of ACM, and ACM induced the uncoupling even in Pi-free medium, an
      increase in the membrane permeability for other ions, such as Na+ and K+, due to
      a different action mechanism has also to be considered. On the other hand,
      positively charged amine local anesthetics, like dibucaine, prevented the
      uncoupling activity by ACM in both Pi and Pi-free medium. The uncoupling activity
      of N-diacetylated ACM lacking free amino groups was ca. 1/120th that of ACM,
      indicating that positively charged amino groups are important for the uncoupling
      activity. It is suggested that some specific interactions between positively
      charged amino groups of ACM and the binding site, which is probably negatively
      charged, are triggers that affect the permeability of the inner mitochondrial
      membrane. Amine local anesthetics may mask the negative charge of the binding
      site, thereby interfering with ACM binding.

PMID- 8882719
TI  - Monoclonal anti-human aldolase C antibodies that react to the isozyme group
      specific sequences and generally conserved sequences of human aldolase C1.
AB  - Nine monoclonal mouse anti-human aldolase C antibodies, mAbs A4, A8, B4, B7, B8,
      C1, D9, E10, and H1, were isolated and characterized. These mAbs fall
      substantially into four groups according to their reactivity with antigens. (i)
      Human aldolase C-specific mAbs (B8, D9, and H1). (ii) Type C aldolase-specific
      mAbs (B4 and E10). (iii) Ubiquitous mAbs, which react with vertebrate aldolases
      irrespective of type of isozyme and species (A4 and B7). (iv) Sub-ubiquitous
      mAbs, which are closely similar to the ubiquitous mAbs but differ slightly in
      terms of antigenic specificity (A8 and C1). Aldolase C-specific mAbs B8, H1, B4,
      and E10, but not D9, have their epitopes on a region within amino acid positions
      79-193 of antigens, where the type-C isozyme group-specific sequence-3 (IGS-3) is
      situated. In contrast, ubiquitous mAbs A4 and B7 and sub-ubiquitous mAb A8 may
      have their epitopes on the commonly conserved regions of the three isozyme
      groups. The epitope of sub-ubiquitous mAb C1 appears to be on the IGS-2/3 but
      this is yet to be resolved. These nine mAbs can be classified into two groups
      based on the mode of epitope recognition, which was determined by ELISA,
      immunoblotting, and immunoprecipitation assays: (i) primary sequence-epitope mAbs
      such as B4, E10, and B7; and (ii) conformation-epitope mAbs (B8, D9, H1, A4, A8,
      and C1). Among these mAbs, aldolase C-specific mAbs H1 and E10 appear to be
      useful as probes for detection of conformational change around the type-C IGS-3
      motif of human aldolase C because, when assessed by immunoprecipitation assay,
      mAb H1 reacts only with human aldolase C but not with CA250 and CA306, while mAb
      E10 reacts with CA250 and CA306 but not with aldolase C, even though these
      antigens have a common type-C IGS-3 motif. Similarly, the ubiquitous mAb B7
      should serve as a probe for general use to detect vertebrate aldolases
      irrespective of isozyme groups and species.

PMID- 8882720
TI  - Change in the expression of hypopharyngeal-gland proteins of the worker honeybees
      (Apis mellifera L.) with age and/or role.
AB  - The roles of adult worker honeybees change with age; young workers nurse brood by
      secreting bee milk (royal jelly), and older workers forage for nectar and pollen
      and process nectar into honey. The electrophoretic profile of worker
      hypopharyngeal-gland proteins changes with age and/or role. Immunoblotting
      analysis using affinity-purified antibodies against three major proteins (50, 56,
      and 64 kDa) of the nurse-bee gland showed that they are synthesized selectively
      and secreted as bee-milk proteins. Immunofluorescence study showed that the
      proteins condense in the duct after secretion from acini. However, a major 70-kDa
      protein synthesized specifically in the forager-bee hypopharyngeal gland was
      identified as an alpha-glucosidase. Therefore, the hypopharyngeal gland seems to
      have two distinct states differentiated by synthesizing of different major
      proteins depending on the age-dependent role change.

PMID- 8882721
TI  - Significance of the chromatin structure in expression of the rat prolactin gene.
AB  - To elucidate the mechanisms underlying cell type-specific expression of the
      growth hormone (GH) and prolactin (PRL) genes, we used rat pituitary-derived cell
      lines producing exclusively GH (GC cells) or PRL (235 cells), and examined the
      following: expression of transcription factors essential for GH and/or PRL gene
      expression; promoter/enhancer activity of the GH and PRL genes transiently
      introduced by transfection; and chromatin structures of the GH and PRL genes.
      Even in PRL-nonproducing GC cells, the PRL promoter/enhancer was more active than
      the GH promoter, and the transcription factors, Pit-1 and estrogen receptor (ER),
      essential for PRL gene expression were functional. The PRL promoter/enhancer of
      GC cells was normal. On DNase I sensitivity analysis of the chromatin structure,
      two hypersensitive sites were detected in PRL gene chromatin of PRL-producing 235
      cells but none in that of GC cells. It thus follows that the major reason for
      absence of the expression of the endogenous PRL gene in GC cells is neither the
      lack of transcription factors necessary for PRL gene expression nor an anomaly of
      the PRL gene itself, but that the chromatin structure of the PRL gene differs in
      PRL-nonproducing and -producing cells. It was shown in this study that neither
      Pit-1 nor ER is required for conversion of the structure of PRL gene chromatin to
      a DNase I-hypersensitive state.

PMID- 8882722
TI  - Molecular cloning and expression of a mouse alpha-1,3 fucosyltransferase gene
      that shows homology with the human alpha-1,3 fucosyltransferase IV gene.
AB  - The polymerase chain reaction was used to amplify and clone a fragment of a novel
      fucosyltransferase cDNA from mouse embryonal carcinoma F9 cells. Southern blot
      analysis of mouse genomic DNA with the cloned cDNA fragment revealed that there
      is a single copy of the fucosyltransferase gene per haploid genome. A 5 kb EcoRI
      restriction fragment of the genomic DNA hybridized with the cDNA has been cloned
      and a 1,697 bp fragment containing the sequence of the cDNA was sequenced. The
      nucleotide sequence and the deduced amino acid sequence of the clone showed a
      highest degree of homology with those of human alpha-1,3 fucosyltransferase IV,
      i.e. 77.1 and 75.5% identity, respectively. Consistent with the sequence
      similarity, the transfection of a 1,544 bp fragment under the control of the
      cytomegarovirus enhancer and beta actin promoter into COS-1 cells confers alpha
      1,3 fucosyltransferase activity on the cells, resulting in cell surface
      expression of SSEA-1.

PMID- 8882723
TI  - Purification and characterization of the DNA-binding domain of BTEB, a GC box
      binding transcription factor, expressed in Escherichia coli.
AB  - BTEB is a GC-binding protein that regulates the transcription of genes with a
      single GC-box or tandemly repeated GC-boxes in the promoter. The DNA-binding
      domain of BTEB consists of three contiguous Cys2-His2 zinc finger motifs and
      short segments adjacent to their N- and C-terminal sides [Kobayashi et al. (1995)
      J. Biochem. 117, 91-95]. The truncated BTEB (residues 120 to 244) containing the
      DNA-binding domain was expressed in Escherichia coli and purified to homogeneity
      under denaturing conditions. DNA-binding activity of the BTEB was regenerated by
      refolding in the presence of Zn2+. The efficiency in regeneration was 70 +/- 10%,
      and the dissociation constant (Kd) of the DNA-complex was 4 +/- 2 nM. Co2+ also
      regenerated the DNA-binding affinity of BTEB, albeit with less efficiency than
      Zn2+. Co-BTEB showed a slightly lower affinity to the specific DNA than Zn-BTEB.
      Refolding in the presence of Cd2+ resulted in an extremely low efficiency in
      regeneration of the DNA-binding activity. Zn-BTEB is in a monomer state at
      concentrations lower than 0.5 microM, and forms a dimer in the concentration
      range of about 10 to 200 microM.

PMID- 8882724
TI  - Cytochrome P450rm from Rhodotorula minuta catalyzes 4-hydroxylation of benzoate.
AB  - Rhodotorula minuta, a red yeast, produces a cytochrome P450, tentatively named
      P450rm, catalyzing the formation of isobutene from isovalerate. We found that
      P450rm interacted with benzoate and the dissociation constant of P450rm for
      benzoate was 36 microM. A reconstituted system that consisted of purified P450rm
      and cytochrome P450 reductase catalyzed the 4-hydroxylation of benzoate in
      addition to the formation of isobutene; the turnover rate was approximately 40
      nmol/min/nmol P450rm. The P450rm-monooxygenase system was specific for benzoate
      and did not catalyze hydroxylation of other aromatic carboxylates. Since only a
      benzoate 4-hydroxylase that requires tetrahydropteridine has been isolated to
      date, P450rm appears to be the first isolated cytochrome P450 that acts as a
      benzoate 4-hydroxylase. The P450rm-monooxygenase system in microsomes of R.
      minuta might function in the degradation of L-phenylalanine on the pathway to
      beta-ketoadipate.

PMID- 8882725
TI  - Isolation and characterization of retinoic acid-inducible cDNA clones in F9
      cells: a novel cDNA family encodes cell surface proteins sharing partial homology
      with MHC class I molecules.
AB  - Rae-1 cDNA is one of the retinoic acid (RA) inducible cDNA clones in mouse
      embryonal carcinoma F9 cells. Rae-1 mRNAs were detected in mouse early embryos,
      but not in various tissues of adult mice. RAE-1 protein apparently consists of
      253 amino acids and is likely to be a glycoprotein consisting of a leader
      sequence, an extracellular domain, a serine, threonine, proline-rich domain, and
      a transmembrane domain. Interestingly, it has a weak, but significant homology
      with major histocompatibility complex (MHC) class I molecules and was
      immunocytochemically identified as a cell surface protein. By determining partial
      nucleotide sequences of 17 Rae-1 cDNAs isolated from the RA-induced F9 cells, at
      least three different kinds of Rae-1 cDNAs were identified and were named Rae-1
      alpha, Rae-1 beta, and Rae-1 gamma cDNAs, respectively. As the overall nucleotide
      sequence homology among these three cDNAs was about 98%, they constitute a novel
      gene family which is likely to be involved in early mammalian embryogenesis.

PMID- 8882726
TI  - Alterations in activity of protein tyrosine phosphatase SH-PTP1 in autoimmune
      MRL/mpj-lpr/lpr mice.
AB  - Activities of protein tyrosine kinase (PTK) and protein tyrosine phosphatase
      (PTP) in autoimmune MRL/MpJ-lpr/lpr mice (lpr mice) were measured and compared
      with the activities in the tissues from MRL/MpJ-+/+ mice (+/+ mice) as the
      control. In the spleen and liver, PTK activities in cytosol and membrane
      fractions were about 1.7- and 1.3-fold, respectively, higher in lpr mice than +/+
      mice. PTP activities in cytosol and membrane fractions from lpr mice were 1.7-
      and 1.3-fold, respectively, higher in spleen, and 2.5- and 1.3-fold,
      respectively, higher in liver compared with those of the controls. These results
      demonstrate that the mutation of lpr gene resulted in elevation of PTK and PTP
      activities. Then, we measured the amounts and activities of SH-PTP1, a cytosolic
      PTP playing a crucial role in intracellular signaling from Fas antigen. The
      amounts of SH-PTP1 were about 4-fold larger in thymus, spleen, and lymphnodes
      than in liver, but there was no marked difference in the amounts between lpr and
      +/+ mice. On the other hand, activity of SH-PTP1 was definitely lower in lpr
      spleen and lymphnodes than +/+ spleen, but several times higher in lpr liver than
      +/+ liver. Tyrosine phosphorylation levels of SH-PTP1 in spleen of lpr and +/+
      mice were similar. However, in liver, it was less phosphorylated in lpr than in
      +/+ mice. This hypophosphorylation might cause the activation of SH-PTP1 activity
      in lpr liver.

PMID- 8882727
TI  - Purification and identification of a novel and four known serine proteinase
      inhibitors secreted by human glioblastoma cells.
AB  - Our previous studies have shown that some human cancer cell lines produce
      pancreatic trypsinogen, plasminogen, and tissue-type kallikrein. To understand
      the regulatory mechanism of these proteinases, serine proteinase inhibitors
      secreted by human glioblastoma cell line T98G were analyzed by gelatin reverse
      zymography with trypsin. The serum-free conditioned medium of T98G cells showed
      more than ten trypsin inhibitor bands ranging from 16 to 150 kDa in the reverse
      zymography. Major trypsin inhibitors were purified by trypsin-affinity
      chromatography. Analysis of their N-terminal amino acid sequences demonstrated
      that the purified inhibitors were identical to the secreted forms of amyloid
      protein precursors (APPs), tissue factor pathway inhibitor (TFPI), placental
      protein 5 (PP5)/TFPI-2, and secretory leukocyte proteinase inhibitor (SLPI). In
      addition, a novel 25-kDa trypsin-binding protein, tentatively named p25TI, was
      identified. p25TI showed weak inhibitory activity against trypsin in reverse
      zymography as compared with the other inhibitors. The secretion of multiple forms
      of serine proteinase inhibitors by human cancer cells raises the possibility that
      they might be involved in the abnormal growth of cancer cells.

PMID- 8882728
TI  - Sex and strain differences in constitutive expression of fatty acid omega
      hydroxylase (CYP4A-related proteins) in mice.
AB  - The constitutive expression of hepatic fatty acid hydroxylase was examined in
      both sexes of ddY mice by measuring the activities of lauric acid omega
      hydroxylase (LAH). The activity of male mice was significantly higher than that
      of female mice. Such a sex difference of hepatic LAH activity was not observed in
      other strains of mice, including BALB/c and C57BL/6. To examine whether decreased
      total P450 activities caused low LAH activity levels in female ddY mice,
      ethoxycoumarin O-deethylase activity, which is exhibited by many P450s, was
      measured in both sexes of mice. This activity had no sex difference. The
      developmental regulation of hepatic fatty acid hydroxylase was then examined by
      making consecutive measurements of LAH activity in ddY mice. The activity is the
      same in immature male and female mice, but is differentiated in the sexually
      mature state. Furthermore, in male mice, orchiectomy caused a dramatic decrease
      in hepatic LAH activity and the activity was restored by testosterone treatment
      to the level of the intact animal. In female mice, ovariectomy and estradiol
      treatment had no effect on the activity, but testosterone treatment caused an
      increase in the activity. The above data are consistent with the constitutive
      expression of CYP4A-related proteins measured by using anti-rat CYP4A1 polyclonal
      antibody. Anti-CYP4A1 antibody inhibited LAH activity, but not lauric acid (omega
      1)-hydroxylase activity. These results suggest that some factors associated with
      male sex hormone are involved in the regulation of hepatic fatty acid omega
      hydroxylase in ddY mice.

PMID- 8882729
TI  - Expression of carbohydrate-binding protein p33/41 in human tumor cell lines.
AB  - We previously reported a new type of lectin, p33/41 (annexin IV), which was
      isolated from a bovine tissue extract [Kojima, K. et al. (1992) J. Biol. Chem.
      267, 20536-20539]. When the expression of p33/41 (annexin IV) was surveyed in the
      lysates of 39 human tumor cell lines by SDS-PAGE, followed by Western blot
      analysis with polyclonal anti-bovine p33/41 and monoclonal anti-annexin IV (Z016,
      Zymed) antibodies, 21 cell lines were found to be reactive with the polyclonal
      antibody, whereas all 39 cell lines were stained with Z016. These results
      together with those obtained with standard proteins, annexins IV and V, suggested
      that the monoclonal antibody, Z016, recognizes annexin V, but not p33/41 (annexin
      IV). Therefore, we performed cDNA cloning of human p33/41 (annexin IV) to prepare
      a recombinant protein and raised monoclonal antibodies against the protein.
      Northern blot analysis with the cDNA as a probe showed that a human colon cancer
      cell line, HT29, contains p33/41 (annexin IV) mRNA of two sizes, 2.0 and 3.0 kb.
      The two monoclonal antibodies, AS11 and AS17, against the recombinant protein
      generated were useful for flow cytometric analysis, ELISA, Western blot analysis
      and immunoprecipitation. Flow cytometric analysis with AS17 showed that p33/41
      (annexin IV) is located in the cytoplasm of HT29 cells, but not on the cell
      surface. However, one of the cell surface proteins first labeled with biotin and
      then solubilized with a detergent was immunoprecipitated with AS17. The results
      suggest the existence of a membrane spanning form of p33/41 (annexin IV).

PMID- 8882730
TI  - Transmethylation reaction is essential for Sarcophaga lectin gene activation.
AB  - Incubation of Sarcophaga fat bodies in buffered insect saline resulted in
      simultaneous activation of multiple defense protein genes [Sugiyama, H. and
      Natori, S. (1991) Eur. J. Biochem. 200, 495-500]. In this study, we demonstrated
      that the addition of both adenosine and homocysteine thiolactone to this medium
      abolished activation of these defense protein genes. As S-adenosyl-homocysteine,
      a potent inhibitor of the transmethylation reaction, is produced in the fat body
      under these conditions, methylation of a certain fat body protein seems to be a
      prerequisite for the selective activation of insect defense protein genes.
      Activation of the HSP70 gene was not interfered with S-adenosyl-homocysteine.

PMID- 8882731
TI  - Identification of five embryonic hemoglobins of rat and ontogeny of their
      constituent globins during fetal development.
AB  - Hemoglobins of rats switch from an embryonic to an adult type during fetal
      development. However, very little is known about the structures and molecular
      species of hemoglobins occurring in the fetal life of rats. In the present study
      we isolated five embryonic hemoglobins, designated E1, E2, E3, E4, and E5, from
      the blood of rat fetuses on day 14 of gestation by ion exchange chromatography.
      Reverse-phase high performance liquid chromatography revealed that these
      hemoglobins each consist of two kinds of globins: E1(11 alpha:epsilon 1), E2(1
      alpha: epsilon 1), E3(zetta: epsilon 1), E4(1 alpha: epsilon 3), and E5(zetta:
      epsilon 3), respectively. The complete amino acid sequences of the zetta, epsilon
      1, and epsilon 3 globins were determined. The zetta globin showed characteristic
      features common in alpha-type embryonic globins of known species in that the N
      terminus is blocked and the amino acid at position 38 is Gln. epsilon 1 and
      epsilon 3 are beta-type embryonic globins, sharing 73.7% amino acid homology.
      Interestingly, they are more similar to the corresponding mouse beta-type
      embryonic globins, y and z, respectively, than to each other, implying that these
      globins have evolved orthologously from common ancestral proteins. It was also
      shown that the zetta, epsilon 1, and epsilon 3 globins are almost completely
      replaced by the adult type alpha and beta globins in the blood of rat fetuses by
      day 18 of gestation.

PMID- 8882732
TI  - Synthetic glycogels for affinity electrophoresis: a facile and efficient method
      for investigating sugar-lectin interaction.
AB  - A novel and efficient method for analyzing sugar-lectin interaction using
      affinity electrophoresis (AEP) is described. Polyacrylamide gels covalently
      conjugated with 2-acetamido-2-deoxy-D-glucopyranose (GlcNAc) residues were
      successfully prepared by radical copolymerization of highly reactive 3-(N
      acryloylamino)propyl 2-acetamido-2-deoxy-beta-D-glucopyranoside with acrylamide
      in the presence of N,N'-methylenebisacrylamide (BIS). When the glycogels carrying
      various densities of GlcNAc branches were employed for polyacrylamide gel
      electrophoresis (PAGE) of lectins, the mobilities of wheat germ agglutinin (WGA)
      were specifically reduced by increasing the concentrations of the GlcNAc residues
      in gels, although concanavalin A (Con A) showed no significant change in the
      mobility. It was also demonstrated that the association constant of WGA with
      immobilized GlcNAc residue can be determined by combined use of this stable
      glycogel and an automated gel-scanning system associated with fluorometric
      spectroscopy. The association constant of WGA with the GlcNAc moiety was
      estimated to be 1.24 x 10(4) M-1.

PMID- 8882733
TI  - Isolation and partial characterization of N-acetyl-D-galactosamine-binding
      lectins from Epiphragmophora trenquelleonis snail.
AB  - A human blood type A hemagglutinating activity was detected in albumin gland
      extracts of Epiphragmophora trenquelleonis snail separated by GalNAc-agarose
      affinity chromatography, of which two N-acetyl-D-galactosamine-binding lectins in
      the extracts were ETL1 was displaced from the affinity column with 1 mM GalNAc,
      and ETL2 with 20 mM GalNAc. Both lectins agglutinated specifically human blood
      type A and AB erythrocytes, but not type B and O erythrocytes. Gel filtration
      chromatography gave a native molecular weight of about 59 kDa for ETL1 and about
      54 kDa for ETL2. On SDS-PAGE under nonreducing conditions, ETL1 showed two
      protein subunits of about 29 and 27 kDa, while ETL2 showed three protein subunits
      of about 27, 24, and 22 kDa. On SDS-PAGE under reducing conditions, both lectins
      showed four protein subunits of 17, 16, 12, and 11 kDa. By Western blot analyses
      developed with biotin-labeled lectins, N-linked oligosaccharides were detected in
      the 17- and 16-kDa protein subunits of ETL1 and ETL2, and in the 12-kDa protein
      subunit of ETL2. O-linked oligosaccharides were detected only in the 11-kDa
      protein subunit of ETL1 and ETL2. On isoelectric focusing both lectins exhibited
      microheterogeneity: ETL1 focused as three protein bands with pIs in the range of
      5.6-6.0, while ETL2 focused as four protein bands with pIs in the range of 6.8
      7.4. We suggest that native ETL1 and ETL2 are glycoprotein complexes with
      molecular weights of 59-54 kDa, composed of two 29-22-kDa nonreduced protein
      subunits held together by noncovalent hydrophobic interactions. Each of the
      nonreduced protein subunits seems to be composed of two 17-11-kDa reduced protein
      subunits held together by interchain disulfide linkages. The main differences
      between ETL1 and ETL2 could be due to different posttranslational modifications
      or to the relative contribution of one or more of their protein subunits.

PMID- 8882734
TI  - Effects of monophosphoryllipid-A on the immunization of mice with keyhole limpet
      hemocyanin- and muramyldipeptide-ganglioside Gfpt1 conjugates.
AB  - Since it was considered that an active immunization against ganglioside Gfpt1
      (IV2Fuc-, II3NeuAc-Gg4Cer) expressed by human small cell lung cancer cells may be
      beneficial in the treatment of this neoplasm in humans, an optimal mode of
      vaccination in model mice was investigated. A novel Gfpt1-muramyldipeptide
      conjugate (Gfpt1-MDP) was synthesized. Its ganglioside carbohydrate-directed
      immunogenicity in mice as measured by serum antibody titers was comparable to
      that of the previously described Gfpt1-keyhole limpet hemocyanin conjugate (Gfpt1
      KLH). Similar immunogenicity was displayed by free Gfpt1 in muramyldipeptide
      phosphoethanolamine-containing phosphatidyl-choline, -serine (PC,PS) liposomes.
      Immunization with Gfpt1-vaccines in the presence of monophosphoryllipid A (MPL),
      in general, raised titers of anti-Gfpt1 antibodies effectively. Immunization with
      PC, PS-liposomes containing unconjugated Gfpt1 and MPL stimulated the highest
      titers observed, thereby effectively preventing tumor growth in Balbc nu/nu-mice
      challenged with human small cell lung cancer cells. However, there was a strong
      crossreaction of these and most other sera with the structurally related and
      widely distributed ganglioside Gtet1 (II3NeuAc-Gg4Cer). Only immunization with
      Gfpt1-KLH conjugate in the presence of MPL stimulated selectively high anti-Gfpt1
      antibody titers showing comparably low crossreactivity to ganglioside Gtet1.

PMID- 8882735
TI  - Successful embryo recovery from swine by a minimal invasive technique.
AB  - An endoscopic embryo flushing technique was elaborated to make possible the
      minimal invasive collection of ova from swine. After experience with pig
      laparoscopy, the method of endoscopic embryo recovery in small ruminants was
      adapted to the abdominal anatomy of swine. Twelve oestrus-synchronized gilts were
      operated 5 days after artificial insemination. In 10 cases both uterine horns
      were flushed by using a Rusch-Gold balloon catheter, flushing cannula and
      atraumatic grasping forceps beside the 10 mm diameter optic. The whole procedure
      took approximately 35-45 min. The average collection rate was 40.4%. According to
      the results, endoscopic embryo recovery can be a useful method in swine
      reproductive research and in top breeding in the future.

PMID- 8882736
TI  - Achievements and difficulties in maintaining the tuberculosis-free status of
      Hungarian cattle herds.
AB  - The tuberculosis-free status of Hungarian cattle herds in the period between 1988
      and the end of 1993 is evaluated. An epidemiological analysis of tuberculin
      tests, laboratory assays and allergic tests yielding positive results, summarized
      in three tables, is given with respect to the cattle population of Hungary. The
      origin of positive reactions obtained in the tuberculin tests was traced in
      different farms of a total of 323 communities. On those farms, the diagnostic
      slaughter and examination of 1,851 breeding animals to exclude or confirm
      Mycobacterium bovis infections involved substantial economic losses. From 25
      outbreaks investigated in the period of study, a total of 191 M. bovis strains
      were isolated from the organs of 21 cattle in 15 household stocks in 14
      communities, as well as from 170 bovine organ samples from large farms of 10
      communities (7 agricultural co-operatives and 3 state farms). In all of these
      cases, infection could be traced back to humans excreting M. bovis. Determination
      of the 2-thiophenecarboxylic hydrazide (TCH) resistance of the isolates
      facilitated the epidemiological investigation. The paper also contains some
      recommendations on the prevention or reduction of losses.

PMID- 8882737
TI  - The value of immunodiagnostic tests in detecting tuberculosis in an infected red
      deer herd and in eradication of the disease by selection.
AB  - The sensitivity and specificity of intradermal tuberculin test (Tb test) were
      studied in an infected red deer (Cervus elaphus) herd (n = 109) in comparison to
      the results of other examinations including gross pathology, histopathology,
      Mycobacterium bovis culture, and the lymphocyte-stimulation test (LST). In our
      case, relative sensitivity was 79.5% and relative specificity was 45.7%. The
      predictive value in negative and positive cases was 80.0% and 44.9%,
      respectively. On the basis of the results obtained, eradication of tuberculosis
      by the selection procedure from a herd of newly captured and colonized deer was
      performed using the Tb test. For the purposes of eradication by selection all
      deer responding to B-PPD were considered positive.

PMID- 8882738
TI  - Detection of ochratoxin a in human blood and colostrum.
AB  - Ochratoxin A (OA) is one of the most frequent sources of mycotoxin contamination
      of feed plants in Hungary. It is produced by 10% of Aspergillus and 12% of
      Penicillium species, i.e. by the widely occurring "commonest" mould species.
      Human exposure to mycotoxins closely resembles that of swine. Fifty-two out of
      100 human blood samples collected at random (52%) were found to contain
      ochratoxin A (0.2-12.9 ng/ml). Recent studies have clearly shown that OA has
      mutagenic, teratogenic and carcinogenic effects. Sensitivity to mycotoxins is
      known to be inversely related to age. Therefore, it was considered important to
      test human colostrum samples for OA content. Thirty-eight out of 92 colostrum
      samples (41.3%) collected from women in the first 24 hours post partum contained
      ochratoxin A (0.2-7.3 ng/ml). The HPLC method applied in this study is described
      in detail.

PMID- 8882739
TI  - Dynamics of Anguillicola crassus (Nematoda: Dracunculoidea) larval infection in
      paratenic host fishes of Lake Balaton, Hungary.
AB  - Anguillicola crassus, a nematode parasitizing the swimbladder of the European eel
      (Anguilla anguilla) caused substantial mortality among eels in Lake Balaton in
      the years 1991 and 1992. Parallel to a 3-year study of the infection dynamics of
      eels, Anguillicola larval infection of paratenic host fishes was also surveyed in
      the lake between 1991 and 1993. During that study, a total of 1,382 specimens of
      22 paratenic host fish species were processed. The results showed that
      anguillicolosis had become a parasitosis widespread throughout the lake, and
      larval infection could be detected in practically all paratenic hosts examined.
      The prevalence and intensity values recorded in the paratenic hosts do not
      completely follow the dynamic change observed during the survey of eel infection.
      During the study of larval infection in paratenic hosts, only inter-species
      differences in the prevalence and intensity of infection could be found, rather
      than the expected course of infection spreading from the West to the East in both
      space and time. Marked differences existed between paratenic host species in the
      degree of host reaction to the larvae.

PMID- 8882740
TI  - Evaluation of blood lipid peroxidation parameters in carbon tetrachloride (CCl4)
      toxicity in sheep.
AB  - Seven female, 2-year-old, nonpregnant, Merino ewes were treated with a nonlethal
      dose of 0.3 ml/kg body mass carbon tetrachloride (CCl4) in 1:1 v/v dilution with
      paraffin oil via a stomach tube into the rumen. Blood samples were collected one
      day before and on the first, second, third, seventh and tenth day after toxin
      exposure to study the changes of the lipid peroxidation (LP) status of red blood
      cell haemolyzate (RBC-haem). The severity of liver damage was monitored by
      determination of aspartate aminotransferase (AST) activity and bilirubin
      concentration in the blood plasma. Twenty-four h after CCl4 exposure all animals
      became lethargic and anorexic, their heart rate and respiratory rate increased.
      On the subsequent two days these signs became more severe, but by the 10th day
      the symptoms disappeared. On the 1st and 2nd day following CCl4 exposure the
      concentration of malondialdehyde (MDA)--an end product of LP--in RBC-haem
      significantly increased. A slight decrease was found on the 3rd, 7th and 10th
      day, but MDA values remained significantly higher than the basal ones. The
      activity of glutathione peroxidase (GPX) in RBC-haem increased slowly on the 1st
      and 2nd day, then it rose intensively on the third day. GPX activity remained
      elevated until the 7th day, but on the 10th day it dropped again. Catalase (Cat)
      activity in RBC-haem did not show any significant changes during the experiment.
      AST activity in blood plasma showed a two-fold increase in the first three days;
      later on the high values decreased. Total and direct plasma bilirubin
      concentration slightly increased on the 3rd day, then both decreased. LP effects
      in CCl4-induced hepatocellular injury were significant in sheep, in line with the
      results of experiments on other species such as rats. The LP effects were
      demonstrated by the elevated MDA concentration and GPX activity.

PMID- 8882741
TI  - Effects of histamine on gizzard erosions and on the activity of selected enzymes
      in chickens.
AB  - Dose- (5, 10 and 15 mg/kg body mass) and time-dependent (2, 6, 12 and 24 h after
      treatment) effects of histamine on gizzard lesions and serum AST, ALT and CK
      activities of chickens are reported. Morphometric results and histopathological
      examination revealed that the most effective histamine dose which induced severe
      gizzard lesions was 10 mg/kg b.m., especially 2, 6 and 12 h after administration.
      No difference from the control values was found after 24 h. That dose also
      induced an elevation of serum enzyme (AST, ALT, CK) activities, which was most
      expressed for the activity of ALT.

PMID- 8882742
TI  - Differences in the thyroxine, triiodothyronine and reverse triiodothyronine
      contents of fetal pig tissues relative to gestational age.
AB  - The concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'
      triiodothyronine (reverse T3) were measured in the liver, kidney and skeletal
      muscles of pig fetuses from day 32 to 113 of age. The iodothyronines were found
      to be present already between days 32 and 39, that is before the onset of fetal
      thyroid function. In the liver, kidneys and skeletal muscles T4 reached maximal
      concentrations at midgestation (days 56 and 93). The T3 level increased with
      gestational age in all tissues examined but, as opposed to T4, its maximal value
      was reached shortly before birth. The rT3 level was the highest between days 85
      and 100 in the liver and kidney; however, in the skeletal muscles it did not
      change with gestation. The presented profiles of change of T4 and rT3 in the
      examined tissues did not correspond to the blood hormone pattern already observed
      in pig, whereas changes in tissue T3 concentrations were similar to those in the
      serum.

PMID- 8882743
TI  - Seasonal variation in the concentration of vitamins A and E in the blood plasma
      of fat-tailed sheep.
AB  - Six non-pregnant ewes and 6 rams (age: 3-4 years) of an Iranian fat-tailed sheep
      breed (Shal) were used. Blood samples were collected monthly for 12 months, and
      the concentrations of retinol and alpha-tocopherol were determined by high
      performance liquid chromatography (HPLC). A limited ration of standard
      composition was fed throughout the year. The ration was supplemented with 25-32
      IU alpha-tocopherol/animal/day. Vitamin A concentrations in the blood plasma of
      ewes were lower in the spring (442 +/- 9 micrograms/L) and summer (452 +/- 7
      micrograms/L) and higher in the autumn (467 +/- 5 micrograms/L). In the rams, the
      plasma concentration of vitamin A was the lowest in the spring (436 +/- 6
      micrograms/L) and the highest in the summer (471 +/- 5 micrograms/L). A seasonal
      comparison did not show statistical differences between consecutive seasons for
      the ewes (P > 0.05). The differences were significant between winter and spring
      (P < 0.05) and spring and summer (P < 0.001) for the rams. The blood plasma
      concentration of vitamin E was 1.21 +/- 0.05, 1.04 +/- 0.05, 1.24 +/- 0.05 and
      1.24 +/- 0.08, mg/L in spring, summer, autumn and winter, respectively, for the
      ewes and 1.24 +/- 0.05, 1.11 +/- 0.06, 1.09 +/- 0.04 and 1.38 +/- 0.07 mg/L in
      spring, summer, autumn and winter, respectively, for the rams. The values were
      significantly different between spring and summer (P < 0.05) and summer and
      autumn (P < 0.01) for the ewes. In rams, the values obtained in autumn also
      showed a significant difference (P < 0.001) from those found in winter.
      Differences between values found in other seasons were not significant (P >
      0.05). The retinol and alpha-tocopherol concentrations of the blood plasma were
      highly similar in the two sexes. The concentrations of retinol in the summer (P <
      0.01) and alpha-tocopherol in the autumn (P < 0.05) showed significant
      differences between the two sexes. The results show that the concentrations of
      vitamins A and E are relatively constant in the blood plasma of fat-tailed sheep
      kept on a standardised feed. However, some differences due to the influence of
      season and sex were observed.

PMID- 8882744
TI  - Variations in the yield, composition and somatic cell count of ewe's milk during
      lactation.
AB  - Variations in the yield, composition and somatic cell count of milk were studied
      in 30 grazing ewes, representing the Pleven F1 x East-Friesian Blackface, Pleven
      F1 and Merino genotypes, during five months of lactation. The somatic cell count
      (SCC) correlated negatively with milk yield and lactose whilst positively with
      milk protein and milk fat, except for Pleven F1 ewes which showed these
      correlations with reversed values. The highest milk yield with the lowest SCC was
      shown by the Pleven F1 x East-Friesian Blackface genotype. Lactose concentration
      varied in a significant negative correlation with the neutral detergent fibre
      content of the grass.

PMID- 8882745
TI  - An understanding of flow- and diffusion-limited vs. carrier-mediated hepatic
      transport: a simulation study.
AB  - Concentration-dependent changes in the hepatic extraction ratio E and tissue
      accumulation of drugs were examined in a simulation study, wherein plasma protein
      binding, flow, and mode of entry were altered. A tubular flow model that
      described carrier-mediated (influx: Kml = 20 microM, Vmax1 = 1000 nmol min-1;
      efflux, Km2 = 200 microM, Vmax2 = 250 nmol min-1), flow-limited (influx clearance
      CLin = efflux clearance CLef = 50 ml min-1), or diffusion-limited (CLin = CLef =
      0.1 ml min-1) hepatocytic entry was employed; drug removal was solely via biliary
      excretion (Km3 = 100 microM, Vmax3 = 1500 nmol min-1). Other parameter space and
      the combination of carrier-mediated transport and passive diffusion were also
      explored. Increased plasma protein binding reduced the hepatic extraction of the
      substrate, and in some instances, constituted the rate-controlling factor,
      especially at lower input concentrations for which tighter binding existed.
      Increased flow rate also brought about a reduction in E, affecting E almost
      inversely when values of E were low (e.g., for the diffusion-limited case or at
      higher input concentration). Tissue accumulation patterns and the apparent tissue
      distribution equilibrium ratio, i.e., tissue to plasma unbound concentration
      ratio Kp, differed among the systems. The behavior of Kp may be used as an
      identifier for the mode of drug transport: A declining (concave-down) Kp curve or
      a parabolic Kp that approached unity with input concentration (Cln) is associated
      with carrier-mediated entry; a rising Kp curve that approaches unity with Cln
      suggests flow limitation; and a waning concave-up Kp curve of very low magnitude
      represents diffusion limitation. Since the unbound tissue concentration (Ct)
      differs from the logarithmic average of the unbound input and output
      concentrations in plasma (Cu) for carrier-mediated and diffusion-limited systems,
      excretion parameters may be obtained only upon fitting of the overall excretion
      rate vs. Ct in the Michaelis-Menten equation; whereas when data are fitted with
      Cu, the rate-limiting step, influx, or deviations of influx, efflux, and
      excretion, will be obtained. When Ct equals Cu, as in flow-limited systems,
      accurate excretion parameters will be provided with the fitting of data against
      either Ct or Cu.

PMID- 8882746
TI  - Stereoselective binding properties of naproxen glucuronide diastereomers to
      proteins.
AB  - The stability of naproxen glucuronide (NAP-G) diastereomers was investigated in
      buffer, 0.3% and 3% human serum albumin (HSA) solutions, and human plasma. R-NAP
      G was found to be less stable in phosphate buffer than its S-diastereomer,
      whereas incubation media containing protein in general increased the degradation
      rate of NAP-G but also caused a change of the stereoselective stability where the
      R-NAP-G was more stable than S-NAP-G. Reversible binding of NAP-Gs to HSA (0.3%)
      was investigated and compared with the corresponding properties of naproxen (NAP)
      enantiomers. NAP-G diastereomers exhibited a considerable and stereoselective
      affinity to HSA, although less than that observed for the NAP enantiomers. In
      vitro irreversible binding of NAP-Gs to HSA, human and rat plasma proteins was
      also investigated. Irreversible binding was higher for R-NAP-G (50 microM) than
      for S-NAP-G (50 microM) in all incubation media. This stereoselective difference
      was observed with HSA containing medium as well as in rat and human plasma.
      Incubation with unconjugated NAP did not lead to irreversible binding.
      Preincubation of HSA with acetylsalicylic acid (approximately 11 mM) and
      glucuronic acid (50 mM) decreased the extent of irreversible binding suggesting
      involvement of lysine residues for covalent binding. Preincubation with S-NAP
      also decreased the irreversible binding yield.

PMID- 8882747
TI  - In vivo pharmacokinetic study for the assessment of poly(L-aspartic acid) as a
      drug carrier for colon-specific drug delivery.
AB  - Glucocorticoids remain one of the mainstays of therapy for acute attacks of
      inflammatory bowel disease despite systemic side effects that limit their use.
      Prodrugs that selectively deliver glucocorticoids to the colon may lower the
      required dose and side effects. Because enzymes of gut microflora are able to
      cleave certain peptide and ester bonds, the ability of an ester prodrug
      consisting of dexamethasone (DX) as model drug and poly(L-aspartic acid) (weight
      average mol wt = 30,000) as drug carrier was investigated to selectively release
      the drug in the large intestine. Prodrug and drug solutions (1.18 mg DX/ml DMSO)
      were administered to two groups of male Sprague-Dawley rats by intragastric
      infusion using an ALZET osmotic pump. All rats were infused for sufficient time
      to achieve steady state in both blood and GI-tract tissues. DX concentrations in
      blood and tissue samples were measured with HPLC. The steady state DX
      concentrations at these sites were used to calculate a drug delivery index (DDI).
      DX blood concentrations were significantly lower (p < 0.05) after intragastric
      administration of the prodrug. Moreover, prodrug administration resulted in
      significantly higher DX concentrations in the cecum and colon mucosa and the
      cecum muscle tissue compared to DX administration (p < 0.05). The prodrug led to
      an increase of the DX concentration in the large intestinal tissues by factors of
      1.3-2.0 and to an 1.3-fold decrease of DX blood concentrations. Thus, this novel
      conjugate should both increase efficacy and reduce toxicity to some extent.

PMID- 8882748
TI  - Estimation of population pharmacokinetics using the Gibbs sampler.
AB  - Quantification of the average and interindividual variation in pharmacokinetic
      behavior within the patient population is an important aspect of drug
      development. Population pharmacokinetic models typically involve large numbers of
      parameters related nonlinearly to sparse, observational data, which creates
      difficulties for conventional methods of analysis. The nonlinear mixed-effects
      method implemented in the computer program NONMEM is a widely used approach to
      the estimation of population parameters. However, the method relies on somewhat
      restrictive modeling assumptions to enable efficient parameter estimation. In
      this paper we describe a Bayesian approach to population pharmacokinetic analysis
      which used a technique known as Gibbs sampling to simulate values for each model
      parameter. We provide details of how to implement the method in the context of
      population pharmacokinetic analysis, and illustrate this via an application to
      gentamicin population pharmacokinetics in neonates.

PMID- 8882749
TI  - [Angiotensin II--receptor antagonists: a new action group for an established
      active principle].

PMID- 8882751
TI  - [In review: medicinal chemistry. Drug development in the last year.
      Antipsychotics. 1].

PMID- 8882750
TI  - [Penicillin--binding protein: the target for beta-lactam antibiotics, beta
      lactamases and their inhibitors].

PMID- 8882752
TI  - [New data: daunoxome against Kaposi sarcoma. Fifth European Conference on
      clinical aspects and treatment of HIV infection].

PMID- 8882753
TI  - Respiratory allergy to parietaria pollen in 348 subjects.
AB  - We have revisited 348 records of allergic outpatients to Parietaria, ratio M/F
      1:1 and mean age 29.46 +/- 12.49 yrs. 97 of them were skin positive to Parietaria
      only (A-group: M/F 37/60); 251 patients were skin positive also to other
      allergens (B-group: M/F 137/114). Mean age of A-group patients (35.41 +/- 12.91)
      was higher than B-group (27.16 +/- 11.54; p < 001). Dividing mono and
      polysensitized subjects by age decade, a different distribution was found between
      the two groups (p < 001): monosensitized patients showed an increasing number of
      subjects from the 3rd to the 4th decade and a decreasing trend in the following
      decades; polysensitized patients showed a prevalence in age < 20 yrs and a
      decreasing trend in the other decades. In B-group Gramineae were the most
      frequent allergens associated to Parietaria (84.8%) followed by Olea Europaea
      (41.1%), Dermatophagoides farinae (37.4%) and Dermatophagoides pteronyssinus
      (36.2%). Main symptoms were rhinoconjunctivitis (187 cases), rhinitis + asthma
      (141 cases) and bronchial asthma (20 cases). Comparing the clinical features of
      the two groups, we have found that monosensitized patients showed a female
      prevalence, a prevalence of rhinitis with late onset of symptoms while in
      patients suffering from isolated asthma the onset was early.

PMID- 8882755
TI  - Local treatment of nasal polyposis with capsaicin: preliminary findings.
AB  - The inflammatory process triggered by the nasal hyperreactivity, whether specific
      or aspecific, presents three components: immunomediation-neurogenic
      interconnection between the nervous and the immunitary systems. Neuropeptides (eg
      SP and CGRP) are among the agents responsible for neurogenic phlogosis and, in
      our opinion, they contribute towards the onset of polyps. Capsaicin, which acts
      on the C fibres, has been applied locally (30 microns) by the AA in 15 patients
      affected by aspecific nasal hyperreactivity with polyps, in the course of a
      double blind study with an equal number of patients. Treatment was given once a
      week for 5 consecutive weeks in order to evaluate the effect on both the
      hyperreactivity and the polyps. Before and after each session and at the 1- and 3
      month controls the following tests were carried out: assessment of symptoms,
      nasal endoscopy, sizing of the polyps, aspecific nasal provocation test and nasal
      cytology. Apart from an improvement in symptoms and in nasal hyperreactivity,
      results showed a reduction in the size of the polyps even though accompanied by a
      gradual increase of eosinophiles which was not correlated to a degranulation
      process.

PMID- 8882754
TI  - Sensitization to neumoallergens influence in mothers of asthmatic children.
AB  - Allergy diseases in our province have the characteristic of early appearance of
      asthma and predominant monosensitization to domestic dust mites due to the
      climatic condition. In this work we study the influence in allergic children. We
      selected 1028 mothers that brought their children to hospital for the first time.
      We divided them in two groups. One was comprised of 459 mothers of atopic
      children (MA) and another of 569 mothers of non atopic children (MC). All mothers
      were skin-prick tested (Phazet). The papula area, the mothers with aeroallergen
      sensitization, were 180 (17.5%) between MA 126 (27.4%) and MC 54 (9.5%). The
      diagnosis of allergic mothers was higher in MA than in MC. Asthma 8.39%, Rhinitis
      4.75% and dermatitis 2%. 53.31% lived on the coast. 51.45% had house moulds. 31%
      had animals. 34.9% were smokers. There were more adverse drug reactions in MA
      than in MC. 180 mothers presented sensitization. D. pteronyssinus 66.3%, D.
      farinae 65.5% Lolium P. 14.55%, Cats 11.6% (MA > MC), Artemisia Vulgaris 6.25%
      and Cladosporium Herbarum 0.6%. There was no correlation between skin
      sensitization and domestic animals. There was no influence between children's IgE
      and mothers with skin sensitization. Skin sensitization to grass pollen
      correlated with the mother who was living in another country. The mothers who
      have been living more than five years in our province presented more skin
      sensitization to aero-allergens.

PMID- 8882756
TI  - Drug fever attributable to Calcium Dobesilate.
AB  - Many drugs may cause fever through different mechanisms, the most frequent being
      hypersensitivity. We are reporting on two cases of drug fever attributable to
      Calcium Dobesilate, a drug used for treating chronic venous insufficiency and
      other vascular disturbances. The diagnosis was made by oral challenge with the
      drug. It reproduced the clinical picture referred to in the anamnesis, including
      hyperthermia. In patient 2 the challenge proved to be useful though she was being
      treated with oral corticosteroids for systemic lupus erythematosus (SLE).
      Cutaneous tests (PRICK and patch tests) were negative with the suspected drug;
      however we think that an immunological mechanism could be responsible for the
      reactions.

PMID- 8882757
TI  - Drug-related Henoch-Schonlein Purpura.
AB  - We report the case of a patient with Henoch-Schonlein Purpura related to a
      treatment with cefuroxime and diclofenac who presented important systemic
      manifestations including a glomerulonephritis with IgA mesangial deposits. Skin
      testing with beta lactam antibiotics and diclofenac were negative in immediate
      and late reaction as well as RAST test to penicillins G and V. No cautious
      administration of drugs was done because of the illness severity. Although a
      reaction to diclofenac could not be excluded we thought that the more probably
      implicated drug was cefuroxime because the patient referred a purpuric rash after
      the intake of cephradine for a mastitis, ten years ago.

PMID- 8882758
TI  - [Asthma and cyclic neutropenia].
AB  - We report a male with history of recurrent infections (recurrent oral aphtous
      disease [ROAD], middle ear infections and pharyngo amigdalitis) every 3 weeks
      since he was 7 months old. At the age of 3 years cyclic neutropenia was diagnosed
      with cyclic fall in the total neutrophil count in blood smear every 21 days and
      prophylactic antimicrobial therapy was indicated. Episodic events every 3 weeks
      of acute asthma and allergic rhinitis were detected at the age of 6 years old and
      specific immunotherapy to Bermuda grass was given during 3 years with markedly
      improvement in his allergic condition but not in the ROAD. He came back until the
      age of 16 with episodic acute asthma and ROAD. The total neutrophil count failed
      to 0 every 21 days and surprisingly the total eosinophil count increased up to
      2,000 at the same time, with elevation of serum IgE (412 Ul/mL). Specific
      immunotherapy to D.pt. and Aller.a. and therapy with timomodulin was indicated.
      After 3 months we observed clinical improvement in the asthmatic condition and
      the ROAD disappeared, but the total neutrophil count did not improve. We present
      this case as a rare association between 2 diseases with probably no etiological
      relationship but may be physiopatological that could help to understand more the
      pathogenesis of asthma.

PMID- 8882759
TI  - Rhinoreactivity in a patient affected by the Darier-White disease.
AB  - The Darier-White disease is a rare hyperkeratosic skin-disease which can also
      affect other organs. From an otoiatric point or view, there are alterations of
      the oral cavity, salivary glands and congenital deafness, but there is nothing
      against the nasal mucosa. The clinical case we studied, shows the presence of
      aspecific nasal hyperreactivity correlated to sun exposure as it happens for
      cutaneous lesions, independently of the presence of eosinophiles in the nasal
      secretion. This could mean that the Darler-White disease can also alter the
      function of the nasal mucosa.

PMID- 8882760
TI  - Hipersensitivity to fruits in latex allergic patients.
AB  - In medical literature, there are many cases reported of anaphylaxis due to
      fruits, before or after allergic reactions to latex. We present two atopic
      patients, with allergy to latex (by clinical history, positive skin test and
      RAST). Both patients showed a positive skin test and RAST to fruits (banana,
      kiwi, avocado and chestnut), but clinically caused no symptoms.

PMID- 8882762
TI  - Historical aspects of nonmelanoma skin cancer.

PMID- 8882761
TI  - Survival up to 5 and 10 years of mexican pediatric patients with systemic lupus
      erythematosus. Overhaul of 23 years experience.
AB  - A retrospective overhaul of all the patients with Systemic Lupus Erythematosus,
      deceased or followed-up for at least 5 years within the Immunology Service of the
      Instituto Nacional de Pediatria (Mexico), since 1970 up to december 1993. The
      objective was to determine overlife of mexican childs attended in a govermental
      institution and secondary to get information about demographic characteristics,
      time from inicial manifestations to diagnosis, treatment received, frequent
      complications, most important sequelas, and deed causes. 65 clinical records were
      reviewed, 86.2% females and 13.8% males, ages from 2 to 18 years old; 20 months
      was the average from start of illnes to definitive diagnosis. Most patient's
      initial treatment was prednisone and cyclophosphamide, being modified according
      to response evaluated by clinical al laboratory follow-up. Fifty one patients
      (78.5%) survived, 60% from 5 to 10 years, and 40% more than 10 years. Fourteen
      patients died (21.5%). Most frequent complications were local and systemic
      infections, hemorragic cystitis and steroidal diabetes. Principal dead cause was
      sepsis. Mortality en Systemic Lupus Erythematosus patients continues being high.
      Many factors contribute for delay diagnosis, in its way responsable for poorer
      pronostic. As a pediatric hospital, follow-up is end at adulthood, what makes
      long term follow-up limited.

PMID- 8882763
TI  - Etiology and pathogenesis of basal cell carcinoma.

PMID- 8882764
TI  - Etiology and pathogenesis of squamous cell carcinoma.

PMID- 8882765
TI  - Histology of basal cell carcinoma.

PMID- 8882766
TI  - Diagnosis of nonmelanoma skin cancer.

PMID- 8882767
TI  - Histopathology of cutaneous squamous cell carcinoma.

PMID- 8882768
TI  - Comparative aspects of nonmelanoma skin cancer.

PMID- 8882769
TI  - Radiation therapy for skin neoplasms.

PMID- 8882770
TI  - Cryotherapy of nonmelanoma skin cancer.

PMID- 8882771
TI  - Mohs micrographic surgery for nonmelanoma skin cancer.

PMID- 8882772
TI  - Principles of reconstruction following excision of nonmelanoma skin cancer.

PMID- 8882773
TI  - Comparison of treatment modalities for basal cell carcinoma.

PMID- 8882774
TI  - Comparison of treatment modalities for squamous cell carcinoma.
AB  - Numerous treatment modalities exist for cutaneous SCC. Having a variety of
      modalities in our armamentarium is useful, but they should be selected carefully
      based on certain key clinical and histologic prognostic factors. The histologic
      parameters should be provided to you by your dermatopathologist and can direct
      the clinician to better tailor treatment to specific neoplasms and thus produce
      more predictable outcomes. By incorporating the available prognostic factors in
      the literature, we can develop a reproducible schema or algorithmic approach to
      the treatment of cutaneous SCC to provide the highest cure rates possible while
      minimizing the morbidity for our patients (see Table 1).

PMID- 8882775
TI  - Focal dermal hypoplasia (Goltz syndrome) associated with intestinal malrotation
      and mediastinal dextroposition.
AB  - Focal dermal hypoplasia (Goltz syndrome) is a rare syndrome comprising
      developmental anomalies of tissues and organs of mesoectodermal derivation. We
      report on a characteristic case of focal dermal hypoplasia with the previously
      unreported association of mediastinal dextroposition and intestinal malrotation.

PMID- 8882776
TI  - FISH detection of chromosome 15 deletions in Prader-Willi and Angelman syndromes.
AB  - We have evaluated fluorescence in situ hybridization (FISH) analysis for the
      clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi
      syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN,
      D15S10, and GABRB3. In a series of 118 samples from patients referred for PWS or
      AS, 29 had deletions by FISH analysis. These included two brothers with a
      paternally transmitted deletion detectable with the probe for SNRPN only. G
      banding analysis was less sensitive for deletion detection but useful in
      demonstrating other cytogenetic alterations in four cases. Methylation and CA
      repeat analyses of 15q11-q13 were used to validate the FISH results. Clinical
      findings of patients with deletions were variable, ranging from newborns with
      hypotonia as the only presenting feature to children who were classically
      affected. We conclude that FISH analysis is a rapid and reliable method for
      detection of deletions within 15q11-q13 and whenever a deletion is found, FISH
      analysis of parental chromosomes should also be considered.

PMID- 8882777
TI  - Thomas syndrome: potter sequence with cleft lip/palate and cardiac anomalies.
AB  - Holzgreve et al. [Am J Med Genet 18:177-184, 1984] first reported on a syndrome
      including renal anomalies, heart defect, polydactyly, and cleft palate with other
      oropharyngeal anomalies. We report here on four sibs with renal adysplasia
      associated in two with cardiovascular malformations and cleft lip or cleft palate
      in two. We propose that these patients as the two siblings reported by Thomas et
      al. [Am J Med Genet 45:767-769, 1993] are affected with a syndrome different of
      the one described by Holzgreve et al. [Am J Med Genet 18:177-184, 1984] mainly
      because of the absence of polydactyly. Thomas syndrome is probably inherited as
      an autosomal recessive trait with marked variability.

PMID- 8882778
TI  - Two sibs with anophthalmia and pulmonary hypoplasia (the Matthew-Wood syndrome).
AB  - We describe two sibs with pulmonary hypoplasia and anophthalmia; one also had a
      number of other malformations. Only one other broadly similar case could be found
      in the literature, and it was an isolated occurrence. The condition is named the
      Matthew-Wood syndrome.

PMID- 8882779
TI  - Mental retardation, epilepsy, short stature, and skeletal dysplasia: confirmation
      of the Gurrieri syndrome.
AB  - We report on a male with severe mental retardation, epilepsy, short stature, and
      skeletal dysplasia. The syndrome was first delineated by Gurrieri et al. in 1992
      [Am J Med Genet 44:315-320]. This case seems to confirm the existence of the
      Gurrieri syndrome.

PMID- 8882780
TI  - Delineation of the Marfan phenotype associated with mutations in exons 23-32 of
      the FBN1 gene.
AB  - Marfan syndrome is a dominantly inherited connective tissue disorder with a wide
      range of phenotypic severity. The condition is the result of mutations in FBN1, a
      large gene composed of 65 exons encoding the fibrillin-1 protein. While mutations
      causing classic manifestations of Marfan syndrome have been identified throughout
      the FBN1 gene, the six previously characterized mutations resulting in the
      severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of
      the gene. We screened 8 patients with either neonatal Marfan syndrome or severe
      cardiovascular complications of Marfan syndrome for mutations in this region of
      the gene. Using intron-based exon-specific primers, we amplified exons 23-32 from
      genomic DNAs, screened these fragments by single-stranded conformational
      polymorphism analysis, and sequenced indicated exons. This analysis documented
      mutations in exons 25-27 of the FBN1 gene in 6 of these patients. These results,
      taken together with previously published FBN1 mutations in this region, further
      define the phenotype associated with mutations in exons 24-32 of the FBN1 gene,
      information important for the development of possible diagnostic tests and
      genetic counseling.

PMID- 8882781
TI  - Unique mosaicism of tetraploidy and trisomy 8: clinical, cytogenetic, and
      molecular findings in a live-born infant.
AB  - We report on a live-born infant with mosaicism of tetraploidy and trisomy 8 who
      had craniofacial abnormalities, cardiac and genitourinary defects, agenesis of
      the corpus callosum, and anomalies of limbs. The infant died at age 14 weeks.
      Molecular studies were done on peripheral blood lymphocytes and cultured
      amniocytes to determine the origin of the cytogenetic abnormalities. On the basis
      of the results, we describe a possible mechanism to explain these abnormalities.
      To our knowledge, this infant represents the first reported case of mosaic
      trisomy 8 with a tetraploid cell line.

PMID- 8882782
TI  - Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)
AB  - Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation
      (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part
      of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS,
      detailed clinical studies including radiographic, neurologic, developmental,
      ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27
      SMS patients. Significant findings include otolaryngologic abnormalities in 94%,
      eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in
      75%, hearing impairment in 68% (approximately 65% conductive and 35%
      sensorineural), scoliosis in 65%, brain abnormalities (predominantly
      ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies
      (especially duplication of the collecting system) in 35%, low thyroxine levels in
      29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The
      measured IQ ranged between 20-78, most patients falling in the moderate range of
      mental retardation at 40-54, although several patients scored in the mild or
      borderline range. The frequency of these many abnormalities in SMS suggests that
      patients should be evaluated thoroughly for associated complications both at the
      time of diagnosis and at least annually thereafter.

PMID- 8882783
TI  - Standard weight for height curves in achondroplasia.
AB  - Standard curves developed for the general population cannot be used to assess the
      growth of an individual who has a condition that results in disproportionate
      short stature. For this reason, efforts have been made to develop growth curves
      specific for several of the chondrodysplasias. However, data concerning weight
      for height have been largely lacking, although they may be of particular
      importance for conditions such as achondroplasia, where there is some consensus
      that an increased prevalence of obesity is a particular problem. In this paper we
      provide standard weight for height curves for males and females with
      achondroplasia, and discuss the use of several indices which have been applied to
      the assessment of body fat in the general population.

PMID- 8882785
TI  - Brachmann-de Lange syndrome: pre- and postnatal findings.
AB  - Brachmann-de Lange syndrome (BDLS) is a well-delineated and relatively common
      syndrome. However, prenatal diagnosis has never been reported, even if in some
      cases ultrasonography demonstrated one or more manifestations of the syndrome. We
      report on 3 cases: in the first 2 cases, prenatal ultrasonography demonstrated
      some signs of the condition. The third represents, to our knowledge, the first
      prenatal diagnosis of BDLS. We also present a review of the literature concerning
      pre- and postnatal findings in this syndrome.

PMID- 8882784
TI  - Linkage of congenital isolated adrenocorticotropic hormone deficiency to the
      corticotropin releasing hormone locus using simple sequence repeat polymorphisms.
AB  - Genetic screening techniques using simple sequence repeat polymorphisms were
      applied to investigate the molecular nature of congenital isolated
      adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare
      cause of hypocortisolism shared by a brother and sister with two unaffected sibs
      and unaffected parents is inherited as an autosomal recessive single gene
      mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol
      sufficiency were investigated for a causal role in this disorder. Southern
      blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin
      (POMC), the ACTH precursor. Other candidate genes subsequently considered were
      those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC
      1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were
      performed using polymorphic di- and tetranucleotide simple sequence repeat
      markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The
      chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC
      1, and NEC-2 were not compatible with linkage. However, 22 individual markers
      defining the chromosomal haplotypes flanking CRH were compatible with linkage of
      the disorder to the immediate area of this gene on chromosome 8. Based on these
      data, we hypothesize that the ACTH deficiency in this family is due to an
      abnormality of CRH gene structure or expression. These results illustrate the
      useful application of high density genetic maps constructed with simple sequence
      repeat markers for inclusion/exclusion studies of candidate genes in even very
      small nuclear families segregating for unusual phenotypes.

PMID- 8882786
TI  - Chromosome 22q11.2 deletion in a boy with Opitz (G/BBB) syndrome.
AB  - This report is on a 14-month-old boy with manifestations of Opitz (G/BBB)
      syndrome in whom a 22q11.2 deletion was found. Deletion analysis was requested
      because of some findings in this patient reminiscent of velocardiofacial (VCF)
      syndrome. The extent of aspiration and of respiratory symptoms in this child is
      not usually seen in VCF syndrome. Opitz syndrome maps to at least two loci, one
      on Xp, the other on 22q11.2.

PMID- 8882788
TI  - Genetic study of scaphocephaly.
AB  - From a series of 1,408 patients with craniosynostosis hospitalized between 1976
      and 1994, 561 probands with non-syndromal isolated sagittal synostosis were
      analyzed. The prevalence of sagittal synostosis was estimated in the order of 1
      in 5,000 children. Family information was obtained from 373 probands distributed
      among 366 families. The male:female ratio was 3.5:1. There was no maternal or
      paternal age effect. In 22 of the 366 pedigrees, a high degree of familial
      aggregation was observed, giving a 6% figure of familial cases. Segregation
      analysis of 253 families indicates that sagittal synostosis is transmitted as a
      dominant disorder with 38% penetrance and 72% of sporadic cases. The frequency of
      twinning was 4.8% with only 1 concordance for sagittal synostosis in a
      monozygotic twin pair. The possibility of a mechanical pathogenesis in sporadic
      cases is discussed.

PMID- 8882787
TI  - Further delineation of the acro-renal-ocular syndrome.
AB  - A triad of acral, renal, and ocular abnormalities was reported previously in four
      families. We report on a fifth family, in which a mother, one of her four sons
      and one of her two daughters are affected. Major findings in the acro-renal
      ocular syndrome are upper limb abnormalities, mainly thumb hypoplasia, eye
      abnormalities such as coloboma and Duane anomaly and renal migration defects. A
      close embryological-temporal relationship between the traits of this entity
      suggest a common monogenic cause. The pattern of inheritance is probably
      autosomal dominant. Because of a wide variability of clinical manifestations,
      recognition of the syndrome in individual cases may be difficult.

PMID- 8882789
TI  - Cerebro-costo-mandibular syndrome.
AB  - We describe two boys with the cerebro-costo-mandibular syndrome (CCMS). Both
      patients presented with Pierre Robin anomaly and respiratory insufficiency and
      died 12 hours and 10 months after birth. The first boy had muscular hypotonia,
      severe micrognathia, glossoptosis, short palate, preauricular tag, paraumbilical
      fibroma, and a small and narrow thorax. His chest roentgenographs showed marked
      hypoplasia of the first to tenth rib, multiple posterior rib-gaps in the only
      four ossified ribs. Tracheomalacia and stenosis of the left ureter was observed
      during autopsy. No structural cerebral anomalies were observed. Respiratory
      distress necessitated a tracheostomy in the second boy. He had severe
      micrognathia with glossoptosis and a cleft soft palate were noted. His chest
      roentgenograph showed a bell-shaped, small thorax with multiple dorsal rib-gap
      defects. CCMS is a rare disorder often associated with Pierre Robin anomaly.
      Chest roentgenographs show the typical posterior rib-gap defects, which are quite
      variable. CCMS usually occurs as an isolated event in a family. Of 41 reported
      families four reports describe horizontal and two describe vertical transmission
      of CCMS. This might imply genetic heterogeneity with autosomal recessive and
      autosomal dominant inheritance. Inter- and intrafamilial expression is variable.
      Careful family studies are necessary before genetic counseling is given.

PMID- 8882790
TI  - Severe form of Freeman-Sheldon syndrome associated with brain anomalies and
      hearing loss.
AB  - We describe a child with whistling face and multiple contractures, including
      ulnar deviation of fingers, compatible with a diagnosis of Freeman-Sheldon
      syndrome (FSS). This patient also presented severe hypertonicity, multiple
      episodes of pneumonia, difficulty in swallowing, and poor weight gain, which are
      characteristic of the most severe cases of FSS. A brain CT scan showed cerebellar
      and brainstem atrophy. Auditory brainstem responses were absent. The child died
      at 5 months of respiratory failure. This case suggests the possibility that,
      especially in the most severe forms, brain abnormalities may be responsible for
      some of the clinical manifestations of this syndrome, i.e., respiratory problems,
      difficulty in swallowing and severe hypertonicity. We assume that there is more
      than one pathogenetic mechanism (muscular, skeletal, and neurological) underlying
      FSS, which, together with the genetic heterogeneity and the wide range of
      clinical symptoms leads us to suggest that it is more appropriate to speak of a
      Freeman-Sheldon spectrum rather than syndrome and that thorough investigation for
      CNS and auditory abnormalities should be part of the initial work-up of these
      patients.

PMID- 8882791
TI  - De novo interstitial tandem duplication of chromosome 4(q21-q28).
AB  - We describe a girl with a previously unreported de novo duplication of chromosome
      4q involving segment q21-q28. Clinical manifestations included growth and
      psychomotor retardation, facial asymmetry, hypotelorism, epicanthic folds,
      mongoloid slant of palpebral fissures, apparently low-set auricles, high nasal
      bridge, long philtrum, small mouth, short neck, low-set thumbs, and bilateral
      club foot. This phenotype is compared with that of previously reported cases of
      duplication 4q.

PMID- 8882792
TI  - De novo direct duplication of chromosome segment 22q11.2-q13.1.

PMID- 8882793
TI  - Upper limb malformations in chromosome 22q11 deletions.

PMID- 8882794
TI  - Opitz G/BBB syndrome: clinical comparisons of families linked to Xp22 and 22q,
      and a review of the literature.

PMID- 8882795
TI  - Opitz GBBB syndrome and the 22q11.2 deletion.

PMID- 8882796
TI  - Interstitial deletion of 11(p11.2p12): a newly described contiguous gene deletion
      syndrome involving the gene for hereditary multiple exostoses (EXT2).
AB  - Individuals with deletions of the proximal portion of the short arm of chromosome
      11 share many manifestations including mental retardation, biparietal foramina,
      minor facial anomalies, and multiple cartilaginous exostoses. The finding of
      multiple exostoses in these patients is remarkable as the disorder hereditary
      multiple exostoses, which is inherited in an autosomal dominant manner, has
      recently been mapped by linkage to three regions, including proximal 11p. We
      report the clinical and molecular findings in an additional patient with an
      11(p11.2p12) deletion. Cytogenetic and molecular analysis demonstrated a de novo,
      paternally derived deletion for markers which have been shown to be tightly
      linked to the 11p locus (EXT2). These data support the location of EXT2 within
      this region and also provide information regarding the ordering of polymorphic
      markers on 11p. Deletion 11(p11.2p12) is a rare, yet specific, deletion syndrome
      involving the EXT2 locus, a gene for parietal foramina, and a mental retardation
      locus, and therefore can be classified as a contiguous gene deletion syndrome.

PMID- 8882797
TI  - Historical evolution and modern implications of concepts of consent to, and
      refusal of, medical treatment in the law of trespass.

PMID- 8882798
TI  - Legal implications of specialty board certification.

PMID- 8882799
TI  - Breaking through the tobacco industry's smoke screen: state lawsuits for
      reimbursement of medical expenses.

PMID- 8882800
TI  - Exclusive contracts: are constructively terminated incumbent physicians entitled
      to a fair hearing?

PMID- 8882801
TI  - Advances in gene technology: molecular biology of human genetic disease.
      Proceedings of the 1994 Miami Bio/Technology European Symposium. Monaco, November
      17-20, 1994.

PMID- 8882802
TI  - Utilization and degradation of an ester-based synthetic lubricant by
      Acinetobacter lwoffi.
AB  - An oil-degrading bacterium, Acinetobacter lwoffi, isolated by elective culture
      from the Medway estuary, utilized an ester-based synthetic lubricating oil
      EMKARATE DE 155 as sole carbon and energy source. Analysis of culture
      supernatants by gas chromatography showed the accumulation of a nondegradable
      metabolite 1,1,1 Tris (hydroxymethyl)propane in addition to two metabolizable
      fatty acids, octanoic and decanoic acids as products of the synthetic oil
      degradation. Esterase activities were subsequently demonstrated in oil and
      acetate-grown cells. The synthetic oil therefore appears to be partially
      biodegradable in the environment.

PMID- 8882803
TI  - The influence of creosote compounds on the aerobic degradation of toluene.
AB  - The inhibiting effect of 14 typical creosote compounds on the aerobic degradation
      of toluene was studied in batch experiments. Four NSO-compounds (pyrrole, 1
      methylpyrrole, thiophene, and benzofuran) strongly inhibited the degradation of
      toluene. When the NSO-compounds were present together with toluene, little or no
      degradation of toluene was observed during 16 days of incubation, compared with a
      total removal of toluene within 4 days when the four compounds were absent.
      Indole (an N-compound) and three phenolic compounds (phenol, o-cresol, and 2,4
      dimethylphenol) also inhibited the degradation of toluene, though the effect was
      much weaker that of the four NSO-compounds. O-xylene, p-xylene, naphthalene and 1
      methylnaphthalene seemed to stimulate the degradation even though the influence
      was very weak. No effects of benzothiophene (an S-compound) and quinoline (an N
      compound) were observed. Benzofuran (an O-compound) was identified as the
      compound that most inhibited the degradation of toluene. An effect could be
      detected even at low concentrations (40 micrograms/l).

PMID- 8882804
TI  - A dynamic river model for biodegradability studies: investigations with selected
      aromatic compounds at low concentrations and comparison with aquatic batch tests.
AB  - The objective of this publication is to present a new dynamic aerobic
      biodegradation test method simulating a river. A laboratory cascade test system
      and standardized batch shake flask tests were used for biodegradation studies
      with the non-volatile and non-sorbing model compounds 2,4-dinitrophenol,
      naphthalene-1-sulphonic acid and sulphanilic acid. To be closer to the often very
      low concentrations of substances in the environment the concentrations of the
      compounds used were standard test concentrations and lower. 14C labelled
      compounds were measured at 50 micrograms/l, capillary electrophoresis at 5000
      micrograms/l and the removal of dissolved organic carbon at 50000 micrograms/l.
      The test results obtained confirmed the known ultimate biodegradability of the
      test compounds and showed that biodegradation degrees, rates and degradation
      durations depended on the test systems, the concentrations of test compounds and
      the inocula. The river model is a suitable simulation test for natural dynamic
      surface waters which can be used to perform biodegradability studies at low test
      concentrations if adequate analytical tools, preferably radioactive-labelled
      substances, are available.

PMID- 8882805
TI  - Metabolism of twelve herbicides by Streptomyces.
AB  - Experiments were conducted to assess the ability of Streptomyces (strain PS1/5)
      to metabolize twelve herbicides representing several different classes including:
      acetanilides, triazines, ureas, uracils, and imidazoles. Incubations in aqueous
      culture with dextrin as carbon source and either ammonium or Casamino acids as
      nitrogen source resulted in transformations (> 50%) of eight of the herbicides
      tested: alachlor, metolachlor, atrazine, prometryne, ametryne, linuron,
      tebuthiuron, and bromacil; the remaining four herbicides (cyanazine, diuron,
      metribuzin, and imazapyr) were also transformed, but to a lesser extent. In most
      instances, biotransformations occurred concurrently with growth and results were
      consistent regardless of the nitrogen source (ammonium vs. Casamino acids).
      However, in some instances there were differences in rates of biotransformation
      as a consequence of the nitrogen source (e.g. alachlor, metribuzin), suggesting
      the selective induction of certain metabolic enzymes; in other instances
      biotransformations were not associated with growth, suggesting secondary
      metabolism. An experiment was also conducted to assess the ability of
      Streptomyces (strain PS1/5) to metabolize atrazine contaminated soil. Inoculation
      of soil amended with 20 micrograms/g of atrazine and 5% chitin as carbon source
      resulted in ca. 78% removal of atrazine within 28 days. These data suggest that
      Streptomyces species may be potential candidates for soil inoculation to
      bioremediate herbicide contaminated soils.

PMID- 8882806
TI  - Biodegradation of atrazine in surface soils and subsurface sediments collected
      from an agricultural research farm.
AB  - The purpose of the present study was to assess atrazine (2-chloro-4-ethylamino-6
      isopropylamino-s-triazine) mineralization by indigenous microbial communities and
      to investigate constraints associated with atrazine biodegradation in
      environmental samples collected from surface soil and subsurface zones at an
      agricultural site in Ohio. Atrazine mineralization in soil and sediment samples
      was monitored as 14CO2 evolution in biometers which were amended with 14C-labeled
      atrazine. Variables of interest were the position of the label ([U-14C-ring]
      atrazine and [2-14C-ethyl]-atrazine), incubation temperature (25 degrees C and 10
      degrees C), inoculation with a previously characterized atrazine-mineralizing
      bacterial isolate (M91-3), and the effect of sterilization prior to inoculation.
      In uninoculated biometers, mineralization rate constants declined with increasing
      sample depth. First-order mineralization rate constants were somewhat lower for
      [2-14C-ethyl]-atrazine when compared to those of [U-14C-ring]-atrazine. Moreover,
      the total amount of 14CO2 released was less with [2-14C-ethyl]-atrazine.
      Mineralization at 10 degrees C was slow and linear. In inoculated biometers, less
      14CO2 was released in [2-14C-ethyl]-atrazine experiments as compared with [U-14C
      ring]-atrazine probably as a result of assimilatory incorporation of 14C into
      biomass. The mineralization rate constants (k) and overall extents of
      mineralization (Pmax) were higher in biometers that were not sterilized prior to
      inoculation, suggesting that the native microbial populations in the sediments
      were contributing to the overall release of 14CO2 from [U-14C-ring]-atrazine and
      [2-14C-ethyl]-atrazine. A positive correlation between k and aqueous phase
      atrazine concentrations (Ceq) in the biometers was observed at 25 degrees C,
      suggesting that sorption of atrazine influenced mineralization rates. The
      sorption effect on atrazine mineralization was greatly diminished at 10 degrees
      C. It was concluded that sorption can limit biodegradation rates of weakly
      sorbing solutes at high solid-to-solution ratios and at ambient surface
      temperatures if an active degrading population is present. Under vadose zone and
      subsurface aquifer conditions, however, low temperatures and the lack of
      degrading organisms are likely to be primary factors limiting the biodegradation
      of atrazine.

PMID- 8882807
TI  - Complete degradation of xenobiotic surfactants by consortia of aerobic
      microorganisms.
AB  - Linear alkylbenzene sulphonates are primarily attacked via a hydroxylation of the
      alkyl chain from the methyl group followed by beta-oxidation. The alkyl chain is
      metabolized by pure cultures to give sulphophenyl carboxylates which accumulate
      in the medium. In mixed culture, other microorganisms are capable of degrading
      sulphophenyl carboxylates. Formation of ethylene glycol monosulphates as major
      products of alkyl ethoxy sulphates demonstrates that the ether bonds are cleaved.
      The bacteria involved in growing on the alkyl chain are unable to utilize the
      hydrophilic moiety. This hydrophilic moiety, in turn, is degraded by other
      microorganisms. The degradation of alkylphenol ethoxylates and highly branched
      alcohol ethoxylates proceeds by shortening the polyoxyethylene chain leaving the
      hydrophobic part of the molecule. The biodegradation of linear alcohol
      ethoxylates and ethoxylated fatty amines is initiated by a central cleavage or
      omega-oxidation. Subsequent oxidation of the alkyl chains results in the
      production of polyethylene glycols and secondary ethoxylated amines. Both polar
      moieties are metabolized by other microorganisms. Degradation of
      alkyltrimethylammonium salts and alkylamines is initiated by a cleavage of the
      Calkyl-N bond. The central fission leads to the formation of alkanals which are
      readily converted by beta-oxidation. The alkyl chain-utilizing bacteria are not
      able to degrade the methylamines. The methylamines, in turn, are subject to
      biodegradation by methylotrophs. The limited metabolic capacities of pure
      cultures of microorganisms utilizing surfactants point to the requirement of
      consortia to degrade surfactants completely. Complete degradation of surfactants
      is accomplished by mixed cultures of microorganisms constructed on the basis of
      synergistic and commensalistic relationships. However, degradation of a
      surfactant by one member of a commensalistic consortium may lead to the
      production of toxic or non-toxic metabolites. Waste water treatment without the
      build up of such metabolites can be achieved in plants operated with sludge
      retention times that are suitable for maintaining all microorganisms of the
      consortium. In contrast, in natural ecosystems the introduction of a surfactant
      may result in a transient formation of a metabolite.

PMID- 8882808
TI  - Transformation and mineralization of halophenols by Penicillium simplicissimum
      SK9117.
AB  - The metabolism of monohalophenols by Penicillium simplicissimum SK9117, isolated
      from a sewage plant was investigated. In submerged cultures, 3-, 4-chlorophenol,
      and 4-bromophenol were metabolized in the presence of phenol. 3-Chlorophenol was
      transformed to chlorohydroquinone, 4-chlorocatechol, 4-chloro-1,2,3
      trihydroxybenzene, and 5-chloro-1,2,3-trihydroxybenzene. With 4-chlorophenol only
      4-chlorocatechol was observed as transient product. A release of chloride ions
      was not observed. Whereas monobromo-, and monochlorophenols could not support
      growth as sole carbon and energy source, growth and release of fluoride ions were
      observed with monofluorophenols as substrates. In presence of phenol, the
      degradation of all monofluorophenols was enhanced. Substrate and cosubstrate
      disappeared simultaneously. 3-Fluorophenol and 4-fluorophenol were completely
      mineralized as shown by the equimolar release of fluoride ions.

PMID- 8882809
TI  - Quantitative structure--activity relationships of the synthetic substrates for
      elastase enzyme using nonlinear partial least squares regression.
AB  - Eighty-nine synthetic substrates for elastase enzyme and its activities (log
      1/Km, log kcat, and log Kcat/Km) are treated using partial least squares (PLS)
      and quadratic partial least squares (QPLS). Chemical features of synthetic
      substrates are described using principal properties (PPs). By using the QPLS
      method, we obtain the nonlinear model equations for three properties (log 1/Km,
      log kcat, and log kcat/km) with the correlation coefficient 0.736, 0.918, and
      0.868, respectively. Also, the predictive correlation coefficients for these
      model equations are 0.640, 0.865, and 0.793, respectively. By this study, it
      becomes clear that the z2 value of the amino acid residue on position A and the
      size of the side chain for amino acid residues on position B are related to the
      properties of the synthetic substrates.

PMID- 8882810
TI  - The neural network as a tool for multispectral interpretation.
AB  - A neural network which utilized data from the infrared spectra, carbon-13 NMR
      spectra, and molecular formulas of organic compounds was developed. The network,
      which had one layer of hidden units, was trained by backpropagation; network
      parameters were determined by a simplex optimization procedure. A database of
      1560 compounds was used for training and testing. The trained network was able to
      identify with high accuracy the presence of a broad range of substructural
      features present in the compounds. The number of features identified and the
      accuracy were significantly greater as compared with networks using data from a
      single form of spectroscopy. The results have significance for the SESAMI
      computer-enhanced structure elucidation system.

PMID- 8882811
TI  - Development of neural network simulator for structure--activity correlation of
      molecules (NECO). Prediction of endo/exo substitution of norbornane derivatives
      and of carcinogenic activity of PAHs from 13C-NMR shifts.
AB  - A perceptron type neural network simulator for structure--activity correlation of
      molecules has been developed with two different learning methods, i.e., back
      propagation and reconstruction methods. First by use of the back-propagation
      method the exo/endo branching of norbornane and norbornene derivatives was
      correctly predicted from the set of 13C NMR chemical shifts for various ring
      carbon atoms. Then the obtained correlation was analyzed by the reconstruction
      learning method. It was shown in this case that the NMR shifts for two carbon
      atoms out of seven have strong correlation with the exo/endo branching. Further,
      structure--activity correlation between the 13C NMR chemical shifts and
      carcinogenicity of 11 polycyclic aromatic hydrocarbons was also analyzed using
      the reconstruction method. It was demonstrated that neural network analysis is
      suitable for the elucidation of complicated structure--activity problems where
      many factors are nonlinearly entangled.

PMID- 8882812
TI  - Stage-specific and cell type-specific aspects of genomic imprinting effects in
      mammals.
AB  - Recent studies have revealed that maternal and paternal alleles of some imprinted
      genes are differentially expressed from the earliest time of expression, with
      virtually no expression from one of the two alleles, while for other imprinted
      genes the normally silent allele can be transcribed during early development. In
      addition, a number of imprinted genes manifest their imprints only in select
      tissues. These observations indicate that the marks that denote parental
      chromosome origin need not directly determine allele expression, but rather bias
      later epigenetic modifications toward a particular allele. Thus, factors
      expressed at specific stages or in specific cell types are required to silence
      one parental allele or another. Stage-dependent and tissue-specific epigenetic
      modifications include the progressive establishment of the mature adult parental
      allele-specific DNA methylation patterns. These changes resemble and may share a
      common mechanistic basis with other epigenetic modifications that occur during
      development. Understanding the mechanisms by which these post-fertilization
      epigenetic modifications are mediated and regulated will be essential for
      understanding how genomic imprinting leads to differences in parental allele
      expression.

PMID- 8882813
TI  - Factors controlling prespore cell differentiation in Dictyostelium discoideum:
      minute amounts of differentiation-inducing factor promote prespore cell
      differentiation.
AB  - Amoebae of strain V12M2 differentiate efficiently into prespore cells without
      cell contact in a salt solution containing cAMP, if the pH of the medium is
      maintained suitably acidic using a restricted buffer [31]. Under such conditions,
      most cells differentiate into prespore cells at pH 5.2. Using this developmental
      system, the elements controlling prespore-cell differentiation were analyzed.
      First, the dependence on cell density was examined. At a very low density (10(2)
      cells/cm2), most cells did not differentiate. As the density was increased the
      proportion of prespore cells differentiating increased, reaching a maximum at 5 x
      10(3) cells/cm2. Conditioned medium could mimic the effects of cell density on
      cell differentiation. These findings suggest the presence of factor(s) released
      into the medium which are involved in inducing prespore-cell differentiation. The
      conditioned medium was found to contain at least two prespore-inducing
      components; one is a novel factor(s) and the other is DIF, which has previous
      only been considered to repress prespore-cell differentiation. These findings
      were supported by experiments using a DIF-deficient mutant, HM44.

PMID- 8882814
TI  - Cell-density-dependent repression of discoidin in Dictyostelium discoideum.
AB  - When Dictyostelium discoideum cells are grown on bacteria, their natural food
      source, the discoidin genes are induced by cell-density-sensing factors before
      the food supply is exhausted [11, 18], and expression increases continuously
      thereafter. This regulation pattern is changed when cells are grown in axenic
      medium: the discoidins are induced at a considerably lower cell density and are
      no longer expressed in stationary phase [13]. We have investigated this
      phenomenon further and show that repression begins when cells are still in
      exponential growth. It occurs at the level of transcription and involves an
      element of the discoidin I gamma promoter for which no function has previously
      been described. Since the effect of high cell density can be mimicked by
      conditioned medium, it appears that the repression is due to an extracellular
      signal. This signal is neither ammonia, nor folate, nor cAMP, the known
      repressors of discoidin expression.

PMID- 8882815
TI  - Persistent correlation between expression of a sulfated carbohydrate antigen and
      adrenergic differentiation in cultures of quail trunk neural crest cells.
AB  - The carbohydrate antigen recognized by monoclonal antibodies such as HNK-1 (first
      characterized as recognizing human natural killer cells) and NC-1 (raised against
      quail neural-crest-derived cells) is found on a number of molecules associated
      with cell differentiation in vertebrates [42]. Previous work has shown that
      subpopulations of cultured quail trunk neural crest cells can be separated by
      fluorescence-activated cell sorting (FACS) on the basis of expression of this
      carbohydrate antigen. When neural crest cells are separated after 2 days in
      culture, adrenergic cells develop preferentially within the HNK-1-reactive
      subpopulation [27]. We wished to investigate whether the capacity for adrenergic
      differentiation remained associated with the HNK-1-positive cell population at
      later times in vitro, when the percentage of HNK-1-reactive cells has declined.
      The present study found that neural crest cells separated according to HNK-1
      reactivity after 4 days in culture also showed preferential development of
      adrenergic cells in HNK-1-positive-enriched cultures, indicating that the HNK-1
      epitope is persistently expressed in vitro on cells with adrenergic potential
      after 4 days of culture. To investigate the possible function of this epitope in
      development of the adrenergic phenotype, HNK-1 was added to unsorted neural crest
      cell cultures. The presence of antibody resulted in a decrease in the percentage
      of HNK-1-reactive cells during the initial 24 h after replating, but had no
      effect on the number of catecholamine-positive cells which developed after 7
      days. We conclude that the epitope recognized by the HNK-1 antibody does not
      appear to function in the induction of the adrenergic phenotype. However, this
      antigenic determinant is useful as a predictive early marker which defines a
      subset of neural crest cells that includes those with the ability to undergo
      adrenergic differentiation.

PMID- 8882816
TI  - Expression of several muscle-specific genes during differentiation of cultured
      quail pineal body cells under artificial (high NaCl) conditions.
AB  - A change in cell differentiation of pineal body cells to cells with myogenic
      features can be induced when such cells are cultured with stepwise increases in
      the NaCl concentration up to a 125 mM NaCl excess. Further differentiation can be
      achieved by changing the culture medium to Cosmedium (serum-free) with the same
      high NaCl concentration. This system is a good candidate as an in vitro model for
      the commitment of pre-myoblastic cells to myogenic cells, and for studies on
      early phases of myogenic differentiation, since the myogenic fate is not selected
      under conventional isotonic culture conditions. Our first step was to analyze the
      expression schedule of an intermediate filament protein, desmin, as an early
      stage marker of muscle differentiation. Desmin expression was detected at a low
      level in mononucleated cells during early differentiation stages (two days in
      medium with a 50 mM excess of NaCl), and a higher order of expression was
      observed in later stages in 20-40% of cells corresponding to myotubes. Expression
      of qmf1 and qmf2 mRNA, quail counterparts of MyoD and myogenin, respectively, was
      detected in two different stages: in the pineal body of 9-day-old embryos and in
      myogenically differentiated pineal cells, by Northern blotting and RT-PCR
      analysis. When pineal cells were transferred to the culture system, qmf1 and qmf2
      expression was not present in isotonic medium and no myogenic differentiation
      occurred under these conditions. However, they reappeared and increased during
      the final stages of myogenic differentiation in the high NaCl medium.
      Furthermore, by use of muscle-specific domain (MSD)-specific antibodies we found
      the expression of a muscle-specific neural cell adhesion molecule (NCAM) species
      at the late stages of differentiation. These results show that the gene
      expression and mRNA splicing patterns of the cells changed from pineal body
      specific to muscle-specific. On the basis of these results, we conclude that this
      system is appropriate for studying the differentiation of non-muscle cells to
      muscle cells.

PMID- 8882817
TI  - Conventional patterns of human intestinal proliferation in a severe-combined
      immunodeficient xenograft model.
AB  - The present work describes the pattern of human intestinal proliferation in an
      immunodeficient murine xenograft model, which we have shown to closely mimic cell
      division in normal paediatric gut. Cellular proliferation was measured using a
      double-label technique combining MIB-1 immunohistochemistry and [3H]thymidine
      autoradiography, to critically compare values for the tissue growth fraction (G1,
      G2, S- and M-phase cells) and DNA synthesizing (S-phase) cells in xenograft
      epithelium, lamina propria, muscularis externa and intraepithelial lymphocytes.
      The MIB-1 monoclonal antibody (which recognises the cell-cycle dependent nuclear
      antigen Ki-67) specifically labelled proliferating human cells within the
      xenografts and did not cross-react with dividing murine cells. This was confirmed
      using ultrastructural in situ hybridisation with human- and mouse-specific DNA
      probes to identify the genetic origin of proliferating cells. In general, we
      found a good tissue correlation between MIB-1 and [3H]thymidine labelling, the
      only exception being an apparent dysregulation of Ki-67 antigen expression in
      regenerating xenograft epithelium. In developed xenograft intestine, the highest
      levels of proliferation were consistently recorded within the crypt epithelium,
      where 15.7%-26.7% of cells were actively cycling and S-phase occupied
      approximately half of the cell cycle. The frequency distribution of proliferating
      epithelial cells within small and large intestinal xenograft crypts was clearly
      tissue-specific, showing typical patterns of cell division. Therefore, the
      presence of functional pluripotent epithelial stem cells and conventional spatio
      temporal patterns in cellular proliferation, migration, de-cycling, lineage
      commitment and cytodifferentiation now makes this an attractive experimental
      model with which to study human intestinal crypt responses to various types of
      tissue manipulation, e.g. cytotoxic, radiotherapeutic, dietary, endocrine and
      gene-targeting therapy.

PMID- 8882818
TI  - [Alternative techniques in coronary intervention--a new differential therapy?].
AB  - Alternative coronary angioplasty techniques have not been applied as often as
      initially supposed. Due to the favorable success rates, complication rates and
      costs, balloon angioplasty is still the gold standard and primary intervention
      procedure. Beyond that, in randomized studies recurrence rates were shown mostly
      higher with newer techniques. Thus alternative techniques are recommendable only
      when balloon angioplasty is unsuccessfull or when a failure is to be expected.
      Today, some niches for alternative techniques can be defined, although they have
      to be confirmed in further randomized studies, particularly since these
      techniques usually require a final balloon dilatation and can give rise to new
      complications.

PMID- 8882819
TI  - [Primary balloon dilatation in every coronary stenosis?].
AB  - The introduction of coronary balloon angioplasty launched interventional
      cardiology. The first 18 years saw significant technical refinements of the
      dilatation catheters. Balloon catheters remained the primary instrument for
      coronary angioplasty in spite of the arrival of various new devices. Only the
      stent has proved really advantageous. The marked increase of coronary angioplasty
      procedures worldwide is based on two facts. First, coronary artery disease is
      being detected increasingly earlier. Second, early states of coronary artery
      disease are treated invasively more and more often. Today, the majority of
      coronary angioplasty procedures is performed in patients who would have been
      treated medically a decade ago. The dominant role of coronary bypass surgery in
      true triple vessel disease has not been challenged. The tendency to perform
      coronary angioplasty in early coronary disease can only be justified if the
      method remains simple or gets even more simple and cost efficient. The increasing
      frequency of angioplasty procedures done during the diagnostic study is tending
      in that direction, as does the decreasing diameter of the material used. At
      present, there is no coronary situation where a new device should be used rather
      than a balloon catheter. Therefore, simple and complex cases should be attempted
      with a balloon first. New devices should only be used in case of a failure of the
      balloon. A frequent failure of balloon dilatation is a menacing dissection for
      which the stent is the therapy of choice. The need for the remaining new devices
      is very small (e.g., rotablator or laser for unpassable or uncrackable stenoses)
      or non existent.

PMID- 8882820
TI  - [High frequency rotational angioplasty].
AB  - High-speed rotational coronary atherectomy is an alternative method to treat
      complex, especially calcified coronary stenoses. A rotating burr tip removes the
      occlusive plaque tissue. The applied rotating frequency is between 160 000 to 190
      000 rpm. The primary technical success-rate for high frequency rotational
      atherectomy alone yields between 50 to 60% on average. Associated with
      consecutive additional balloon angioplasty, the success rate is between 80 and
      95% when treating complex type B II or C stenoses. Today, the usage of a single
      burr tip size with adjunctive balloon angioplasty has become a standard
      procedure. The occurrence of serious complications such as extensive dissections
      or thrombotic vessel occlusion is a rare phenomenon after high-speed rotational
      atherectomy compared to coronary balloon angioplasty, whereas coronary spasm is
      more common after high-speed rotational atherectomy. According to the actual
      results, high-speed rotational angioplasty did not lower the rate of long-term
      restenosis, compared to the results achieved by balloon angioplasty alone. The
      rate of long-term restenosis is reported to be between 40 to 50% after highspeed
      rotational angioplasty with or without adjunctive balloon angioplasty.

PMID- 8882821
TI  - [Value of rotational ablation in reopening chronic coronary artery occlusion].
AB  - Previous studies, including our own prospective study (634 patients), on chronic
      coronary artery occlusion demonstrated the highest success rate in reopening by
      primary use of conventional guidewire technique. The present prospective
      randomized study in 124 patients investigates the role of high-speed rotational
      angioplasty after primary guidewire-recanalization in comparison to sequential
      PTCA. Early results were described by analyzing the residual degree of stenosis,
      early dissection, stabile dissection at the end of procedure, complicated
      dissection, necessity of stent implantation, acute re-occlusion, restenosis or
      reocclusion during recoronary angiography after 24 h, and infarction. Despite the
      advantage of rotablation with significant reduction of early and stabile
      dissections (p < 0.01) only slight difference in restenosis-rate and comparable
      results for the rest parameters were achieved. CONCLUSION: Results of this study
      demonstrate no advantage in using rotablation after recanalization of chronic
      coronary occlusion in comparison to sequential PTCA.

PMID- 8882822
TI  - [High risk PTCA: prevention and treatment of cardiogenic shock with mechanical
      assist systems].
AB  - Vessel occlusion during of after PTCA integrates the risk of pump failure if the
      ischemia volume is great as compared to the remaining myocardium. In so-called
      high-risk PTCA a risk stratification by means of risk scores such as "Bergelson
      Score" is mandatory. To encounter the risk of pump failure the application of
      mechanical cardiac assist devices such as balloon pumps, Hemopump or percutaneous
      applicable cardio-pulmonary support (pCPS) can be considered. To counteract
      ischemia during balloon inflation active perfusion balloons can be applied. The
      latter systems are simple and effective, however the duration of application is
      restricted to the balloon inflation period. Cardiac assist devices are more
      aggressive. While the results of intaaortic ballon pump in combination with high
      risk PTCA are unsatisfying, Hemopumps and pCPS were alternatives, although the
      Hemopump is still under investigation. Our own results on 42 patients with high
      risk PTCA demonstrate an acceptable 8.6% hospital mortality rate, however an
      unsatisfying intermediate survival rate since a complete revascularisation in
      this subset of patients with extensive coronary disease and, frequently, total
      vessel occlusion is mostly impossible.

PMID- 8882823
TI  - [Applications and value of intravascular ultrasound imaging in coronary
      interventions].
AB  - Intravascular ultrasound (IVUS) is a twodimensional imaging technique that
      provides crossections of the coronary artery with a high spatial resolution and
      therefore became the new gold standard for quantifying complex lesions. The
      detailed information about vessel and lumen dimensions before and particularly
      after angioplasty is of high clinical value, because the acute luminal gain is an
      important predictor of restenosis. At the moment IVUS is the only way of
      analyzing the plaque composition in vivo. This allows plaque-specific
      interventional therapy of coronary lesions with balloon or modern alternative
      angioplasty techniques like directional atherectomy, rotational atherectomy,
      stenting or a combination of these. IVUS can also quantify the plaque burden in
      angiographically normal reference segments during balloon angioplasty and
      stenting. This often leads to the use of larger balloon diameters than those
      chosen by angiographic measurement of the reference segments. For stenting the
      prognostic significance of this additional luminal gain could be shown, for other
      interventional procedures this is currently being investigated in controlled
      studies.

PMID- 8882824
TI  - [Conventional therapeutic strategy in PTCA-induced dissection: long-term re-PTCA,
      early re-coronary angiography].
AB  - A prospective randomized trial in 324 patients (pts.) analyzed the early clinical
      course of stabile dissections (stabile perfusion, degree of residual stenosis >
      50% < 70% and stabile early result after 24 h). The results of quantitative
      recoronary angiography after 6 weeks and 3-4 months with differentiated
      reintervention (long time-PTCA, atherectomy, stent, CABG) were analyzed to
      determine the early clinical course. 57% of pts. demonstrated a type-I dissection
      (excentric stabile dissection with quantifiable degree of residual stenosis). By
      early recoronary angiography after 6 weeks with differentiated reintervention 68%
      of pts. (125 pts.) showed a sufficient result after 3.8 months. In 51% of pts. an
      additional sufficient result could be achieved by a second reintervention after
      1/4 year. Considerable complications (infarction, CABG, acute death) occurred in
      2.7% of pts. with type-I dissections. 108 pts. (33%) could be classified with
      type-II dissection (diagonal flap). Sufficient result after 3.5 months could be
      achieved in 84% pts. In 20 of 22 pts. an additional successful reintervention
      could be performed. The complication-rate (infarction, CABG) was 5.5%. In pts.
      with type-IV dissection (complex dissection) the early clinical course was more
      unfavorable with higher restenosis rate and considerable complications of 10%.
      The rare type-III dissection (short spiral dissection) showed a high recurrence
      rate already after 6 weeks (33%) and sufficient results after 3.2 months only in
      42% of pts. Complication rate was high with 50% (2 x deaths, 2 x CABG).

PMID- 8882825
TI  - [Directional coronary atherectomy in coronary dissection?].
AB  - Significant local dissection at the site of angioplasty remains the most common
      cause of complications at balloon dilatation. In the past, the only solution was
      to transfer the patient for emergency coronary artery bypass grafting. Recent
      improvements in equipment and increasing experience mean that alternative
      instrumental methods are now available to manage dissection; in particular, by
      directional atherectomy and stent implantation, thus possibly avoiding surgery.
      In this article, the use of atherectomy as management for acute local dissection
      will be discussed, with special reference to the potential difficulties which may
      be encountered. Data showing that excellent immediate results and good long-term
      success can be achieved with atherectomy for acute dissection using careful
      selection criteria will be presented, indicating that atherectomy is a valid
      alternative instrumental treatment for the management of such dissection.

PMID- 8882826
TI  - [Direct coronary bypass operation in complicated coronary dissection].
AB  - Improvement of interventional techniques, sophisticated patient selection, and
      individual experience has decreased the probability of emergency operative
      revascularization of increasing numbers of PTCA cases in recent years. This rate
      is now between 0.5 to 3%, including highrisk dilatations. Dissection is the most
      common complication of PTCA, while perforation is rare. Patients with high risk
      for PTCA-procedures (age, concomittant diseases, female gender) are, in general,
      risk patients for operative revascularization. The postoperative course of
      emergency bypass surgery after PTCA-complication (infarction rate, mortality) is
      dependent on duration and severity of the myocardial ischemia and preoperative
      circulatory function. Complete revascularization in cases of multi-vessel disease
      and the use of the internal mammary artery as a graft vessel is being achieved in
      increasing numbers.

PMID- 8882827
TI  - [The significance of intravascular ultrasound in differential diagnosis and
      therapy of coronary stenoses].
AB  - Intravascular ultrasound (IVUS) has emerged from being a research tool to
      becoming an important aspect in invasive cardiology, because it offers the
      possibility to obtain "in vivo" histology, including the vessel wall, while
      angiography allows for lumenograms only. The reasons for performing IVUS can be
      divided into either diagnostic or intervention associated indications. Diagnostic
      strength of IVUS is the ability to monitor compensatory coronary artery
      enlargement as a response to arteriosclerosis, to reveal occult left main stem
      disease, and angiographically "silent" arteriosclerosis. The peri-interventional
      potentials of IVUS are the ability to allow optimal device selection, i.e.,
      rotablators in calcified lesions or atherectomy devices in large plaque burden.
      The effects of PTCA on vessel wall morphology can be studied in great detail and
      the effect on true luminal gain assessed almost on-line. Several groups showed
      that the residual plaque area after angiographically successful PTCA lies in the
      range of 60%. A significant reduction of this number may influence long-term
      outcome after PTCA. Minimal luminal areas after PTCA seem to be an indicator of
      restenosis, while the morphological appearance alone seems to be less predictive.
      Intravascular monitoring of stent implantation led to high-pressure stent
      deployment with significant increase in postprocedural luminal diameters and,
      finally, the ability to withold anticoagulation in patients with optimal stent
      deployment. Furthermore, integrated devices, like balloons on IVUS catheters,
      steerable catheters, integrated flow measurements and pressure transducers will
      further increase the usefulness of IVUS.

PMID- 8882828
TI  - [Coronary laser angioplasty: clinical value and experimental progress].
AB  - From 1988 to 1995, approximately 10,000 patients with coronary artery disease
      have been treated using excimer laser angioplasty. All data underline the
      feasibility and safety of this technique. However, coronary excimer laser
      angioplasty has been performed as a stand-alone procedure in a minority of
      patients, only, either due to an insufficient angiographic result, or due to
      complications such as abrupt vessel closure, severe dissection or perforation.
      Clinical and angiographic follow-up studies have also documented that excimer
      laser angioplasty does not reduce the incidence of restenosis following the
      coronary intervention. Experimental results underline the importance of pressure
      waves and bubble formations, which can cause additional vessel wall trauma
      despite thermal injury. Promising new laser devices should offer high ablation
      rates with only minimal thermal and acoustic tissue injury. It is expected that
      such laser devices will emit in the mid-infrared spectrum of light.

PMID- 8882829
TI  - [Concepts for local therapy of restenosis].
AB  - Local drug delivery is a new therapeutic approach targeted at the prevention of
      restenosis after coronary balloon angioplasty. Several mostly catheter-based
      devices have been designed to deliver medications with, for example,
      antithrombotic or antiproliferative actions directly at the site of angioplasty.
      Besides delivery of conventional pharmacologic agents, novel therapeutic
      strategies based on molecular mechanisms (e.g., gene transfer or antisense
      oligonucleotides) are currently under investigation and at the threshold of
      clinical trials. In addition, local radiation with either radioactive wires or
      stents has shown promising results in first experimental studies. More
      investigations are necessary, however, to clearly demonstrate the efficacy of the
      various local delivery approaches, with a special emphasis on safety aspects.

PMID- 8882830
TI  - [Treatment of recurrent stenosis by conventional re-PTCA].
AB  - Balloon angioplasty for restenosis has a higher success rate and a lower
      complication rate as compared to PTCA in de-novo-lesions. The restenosis rate
      after a second or third PTCA is only slightly higher than after a first PTCA. So
      far, balloon dilatation is the most effective and most economic treatment for
      restenosis.

PMID- 8882831
TI  - Racism and health: a research agenda.

PMID- 8882832
TI  - Toward a conceptualization of race in epidemiologic research.
AB  - This paper is a review of the prevailing conceptual basis of the use of race in
      health research. The author explores the current definitions of race in health
      research, and describes some of the history of race fabrication. In the
      examination of the association between race and disease the author describes
      black/white differences in age-adjusted mortality, infant mortality rates and
      birthweight. The analysis of race and disease is frustrated by incomplete
      theoretical constructs. Race, as used in health research, tends to be a
      unidimensional construct and the complex interplay between race and other social
      status variables is simplified. These problems are illustrated, and the author
      suggests a multidimensional construct of race.

PMID- 8882833
TI  - Why we should continue to study race...but do a better job: an essay on race,
      racism and health.
AB  - For at least a century, American medical and public health researchers have used
      race as a marker for biology, and have documented race-associated differences in
      health and illness behavior. The research has often been inappropriate and has
      led to abuses and erroneous conclusions about the role played by race in the
      production of disparities in health status. Consequently, some researchers have
      begun to advocate the abolition of medical and public health research using race.
      In this essay, I argue that, although the arguments against continuing to study
      race have some merit, more rather than fewer studies of race are needed.
      Researchers should be more careful in the use of race and more conscious of the
      limitations of the race concept.

PMID- 8882834
TI  - Institutional racism and the medical/health complex: a conceptual analysis.
AB  - Presented in this paper is a theoretical framework for understanding and applying
      the concept of institutional racism to the medical/health care system. Medicine
      and health are viewed as vital social institutions that reflect the norms, values
      and social stratification systems of the larger society. Institutional or
      systemic patterns of racism are legitimated and promulgated through accepted
      standards, criteria, and organizational processes within the medical health
      complex that have the effect of discriminating against the minority group. It is
      maintained that racism is manifested (overtly or covertly) through history,
      ideology, community relations, research, education and the professions, and
      differential treatment. Focusing on investigators who have conducted studies of
      "racial bias" in the diagnosis and treatment of coronary artery disease, the
      author discusses some of the shortcomings of this research, from an institution
      racism perspective. Differential treatment researchers are encouraged to include
      social theory as part of their analysis and to explain the practical significance
      of their findings for the equitable delivery of health care. It is suggested
      that, because of wider structural changes occurring in American society, issues
      related to racism within medical and health institutions will become increasingly
      more important.

PMID- 8882835
TI  - Racism and perinatal addiction.
AB  - Recent publicity and policy have targeted drug use by non-white women,
      particularly during pregnancy and parenthood. This emphasis on women of color is
      discordant with the population demographics of substance use and addiction,
      although morbidity and mortality related to drugs is often greater among
      nonwhites. Women with addictive disorders that are exacerbated by their social
      environments are blamed for their behavior. Meanwhile, drug treatment and primary
      health care services for these women are woefully inadequate. Among newborns
      testing positive for cocaine, those with black mothers are more likely to be
      discharged to non-maternal care, which may perpetuate family disruption. There
      are multiple reasons for true and perceived ethnic differences in substance use,
      addiction, and related social and medical harm. Such harm may be worsened by the
      racism inherent in U.S. drug policy. The scapegoating of non-white drug-using
      women and the paucity of treatment for them may be related to political and
      economic imperatives of society in maintaining and pacifying exploited groups.

PMID- 8882836
TI  - Are black Americans entitled to equal health care? a new research paradigm.
AB  - This paper analyzes the health, economic and legal implications of most major
      health systems' reform initiatives in the 20th century and, briefly, the 19th
      century. The paper suggests that models of analysis grounded in science deter the
      development of claims for racial equality in health care. Because race is a legal
      construct, the paper suggests that the 14th Amendment's Equal Protection Clause
      is an analytical framework that better accommodates the complexity of the health
      system, is at the heart of our national laws and ethos, and has political
      rhetorical power to further the political and policy debate. Major components of
      the health care system, including professional training, hospital construction,
      and health care financing, are analyzed for racially discriminatory purpose or
      impact and the extent of government participation. The paper gives particular
      attention to: the Flexner Report and the limited number of black physicians; the
      Hill-Burton program and the disproportionate assistance it gave to white
      controlled hospitals; and, efforts to expand health insurance coverage that also
      disproportionately favored the needs of the white community. Given the
      compounding effects of numerous policy decisions made over many years, there
      should not be any great wonder that such gross disparities in morbidity and
      mortality exist between black and white Americans. Further research and analysis
      of the policy decisions that have constructed the current health care system as
      well as framing those analyses as claims for racial fairness will better develop
      the policy debate than more narrowly focused analytical models from biomedical
      science or epidemiology. The law produced slavery and segregation, which usually
      determined where you lived, where you went, what work you could do, and what you
      learned. That legally constructed system significantly determined what you earned
      and what health you had. The biomedical models of analysis of our health system
      are too narrowly focused and temporally limited to identify the broad systemic
      barriers to equal health and health care. An analytical framework from law more
      easily accommodates the complex dynamics of our health care system. The equal
      protection clause of the 14th amendment has been used to analyze complex social
      and economic models, such as housing and education and has moved those systems to
      greater racial equality. The equal protection clause is at the heart of our
      national laws and ethos and, as a claim for fair treatment from government, has
      considerable rhetorical power. Menefee presents an analysis of major health
      policies dealing with training of physicians, construction of hospitals, and
      financing of personal health care. He suggests it demonstrates a health system
      rooted in racial discrimination and perpetuating racial discrimination in
      education, employment and housing. The history of successes using this analytical
      framework in other areas of social policy validates its consideration by health
      policy analysts for further research.

PMID- 8882837
TI  - Racism and children's health: issues in development.
AB  - It has been posited by some social scientists that racism has a negative impact
      on the health of certain minority groups in the United States. How racism affects
      the development of children and thus their health, has not been addressed by
      research in developmental psychology, despite a plethora of studies of
      racial/ethnic identity development. Existing developmental theories may be
      amenable to describing and possibly predicting the role that racism plays on
      child and adolescent development. A model is presented that attempts to explain
      how racism might affect a child's development and consequently his health by
      incorporating and synthesizing various developmental principles and social
      cognition theory. The need for empirical inquiry on this topic is indicated;
      design suggestions are offered.

PMID- 8882838
TI  - Target marketing of tobacco and alcohol-related products to ethnic minority
      groups in the United States.
AB  - This paper examines whether increased consumption of tobacco and alcohol products
      by minority groups is a function of the target marketing campaigns directed at
      these groups by marketers, and whether such contributes to the perpetuation of
      racism. First, a description of the tobacco and alcohol consumption rates of
      blacks and Hispanics compared to whites is presented, including a comparative
      analysis of the health effects and mortality rates resulting from the consumption
      of tobacco and alcohol. Second, the paper examines specific marketing strategies
      of targeting tobacco and alcohol products to ethnic minority consumers. This is
      followed by a discussion of whether these practices are a deliberate strategy
      driven by racism or just the pursuit of profit. A framework for answering the
      question is provided. Finally, the paper assesses the prospects for change in the
      future, and analyzes specific needs for future research.

PMID- 8882839
TI  - Segregation, discrimination and mortality in U.S. blacks.
AB  - Theoretically, segregation and discrimination could affect mortality among blacks
      (African Americans) not only through their impact on social class (including the
      concentration of blacks in high-poverty areas) but also by influencing health
      care and psychosocial factors. This paper reviews evidence that variation in
      mortality rates for black infants and young adults living in large metropolitan
      areas is associated with the level of black-white segregation. A few metropolitan
      areas in California with relatively low levels of segregation are shown to have
      low black death rates and small black-white differences in mortality rates for
      infants and young adult males (15-44 years old). In-depth studies are needed in
      these areas. Longitudinal studies of potential "risk factors" for disease and
      death among blacks should include: personal histories of experiences with
      discrimination, psychological reactions to discrimination, segregation indexes,
      quality of life in residential areas, and social class indicators.

PMID- 8882840
TI  - Affective and physiological responses to racism: the roles of afrocentrism and
      mode of presentation.
AB  - Recent experiments have examined the subjective and physiological responses of
      African Americans to racism using video-taped vignettes or emotional imagery.
      These studies reported changes in mood and increases in cardiovascular (CV) and
      electromyographic (EMG) activity when analogs of the stressful situations were
      encountered. In addition, individual differences in responses were found to be
      related to various personality measures. The present study examined the mood, CV
      and EMG responses of 60 African-American women as they encountered social
      situations that included blatant and more subtle forms of racism. Half of the
      sample viewed both vignettes while the remainder imagined them. The relationship
      between responses and Afrocentrism, a measure related to black identity, was
      examined. Significant changes in heart rate, digital blood flow and facial muscle
      activity in the corrugator regions resulted. The most pronounced changes occurred
      when blatantly racist material was encountered. Mood changes tended to be
      stronger when material was imagined versus viewed. In general, Afrocentricity was
      not related to physiological responses to the scripts, though mood responses and
      Afrocentricity were related in several instances. The findings indicate that CV,
      as well as EMG and mood responses, are sensitive to various forms of racism
      presented in imagery and video modes.

PMID- 8882841
TI  - Gender differences in mood and cardiovascular responses to socially stressful
      stimuli.
AB  - Filmed vignettes of socially stressful situations elicit changes in emotional
      states and physiological activation. Several studies have reported changes in
      mood and physiological activity in African Americans who encountered laboratory
      analogs of stressful situations. However, none have examined gender differences.
      African-American college students (52 women and 40 men) viewed two versions of
      one of two social stressors. In one instance, the perpetrator of the stressful
      circumstances was Caucasian, while in the other, a Black perpetrator was viewed.
      Order of viewing was counterbalanced. The scenes depicted either an unjust arrest
      for shoplifting or an encounter with a rude and threatening highway patrolman.
      Analyses of variance determined that increases in blood pressure occurred as the
      stressful scenes were viewed, though no increases occurred in response to the
      neutral material. Women reported more tension, distress and fear during the
      stressors while the men evidenced more pronounced elevations in blood pressure.
      The findings encourage further study of the impact of social stress on
      physiological and emotional processes.

PMID- 8882842
TI  - Racism and the physical and mental health status of African Americans: a thirteen
      year national panel study.
AB  - This paper examined the relationships between the experiences and perceptions of
      racism and the physical and mental health status of African Americans. The study
      was based upon thirteen year (1979 to 1992), four wave, national panel data (n =
      623) from the National Survey of Black Americans. Personal experiences of racism
      were found to have both adverse and salubrious immediate and cumulative effects
      on the physical and mental well-being of African Americans. In 1979-80, reports
      of poor treatment due to race were inversely related to subjective well-being and
      positively associated with the number of reported physical health problems.
      Reports of negative racial encounters over the 13-year period were weakly
      predictive of poor subjective well-being in 1992. A more general measure of
      racial beliefs, perceiving that whites want to keep blacks down, was found to be
      related to poorer physical health in 1979-80, better physical health in 1992, and
      predicted increased psychological distress, as well as, lower levels of
      subjective well-being in 1992. In conclusion, the authors suggested future
      research on possible factors contributing to the relationship between racism and
      health status among African Americans.

PMID- 8882843
TI  - The health consequences of racial discrimination: a study of African Americans.
AB  - This investigation focuses on the relationship between racial discrimination and
      health. Many studies have shown a link between race and differential health
      outcomes, but few have actually measured racial discrimination. Such studies
      leave unanswered the question of exactly how the experience of racial
      discrimination might affect health. Racial discrimination is argued to act in the
      same fashion as other chronic stressors by increasing blood pressure. However,
      racial discrimination may also give rise to the sense of thwarted aspirations,
      itself a stressor, and make the active coping style of "John Henryism" more
      likely. In these data, we measure perceived racial discrimination for a sample of
      African Americans and find that experiencing racially-based discriminatory
      treatment does not impact health. There is no relationship between doctor
      diagnosed hypertension and cardiovascular disease, and being the victim of
      racially biased treatment. We discuss possible reasons for this, and argue that
      greater conceptualization about the postulated link between discrimination and
      health is necessary, as well as explicitly designed studies for the purpose of
      examining this postulated relationship.

PMID- 8882844
TI  - The perceived racism scale: a multidimensional assessment of the experience of
      white racism among African Americans.
AB  - The experience of racism is a complex, multidimensional phenomenon. At present,
      there are few instruments that attempt to capture the experience of racism in all
      of its complexity. For this study, a new instrument, the Perceived Racism Scale,
      has been constructed to assess the experience of racism in African Americans in a
      multidimensional manner. The scale not only provides a measure of the frequency
      of exposure to many manifestations of racism (including individual and
      institutional, overt and covert, attitudinal, behavioral, and cultural), but
      takes a step forward in more comprehensively measuring the experience of racism
      by assessing emotional and behavioral coping responses to racism. These responses
      are measured with respect to exposure to racism in three situational domains: on
      the job, in academic settings, and in the public realm. Measurement of responses
      to a fourth domain, that of exposure to racist statements, is also included. It
      is hoped that the Perceived Racism Scale will facilitate a more comprehensive
      understanding of the experience of racism among African Americans and, through
      its use in research and clinical settings, will ultimately move us closer to
      reducing the prevalence and potentially untoward effects of racism.

PMID- 8882845
TI  - Racism and the mental health of African Americans: the role of self and system
      blame.
AB  - The research on external (social system) and internal (personal) attributions to
      mental health outcomes for African Americans is reviewed. Although many blacks
      have aspirations that they are unable to achieve, the motivational and mental
      health consequences of this situation are unclear. Several researchers have
      suggested that it is adaptive for African Americans to reduce striving effort and
      bring personal goals more in line with the objective realities of an unfair
      opportunity structure. Others have proposed that because an unjust system is to
      blame, the most appropriate response is to work collectively with other group
      members to make the system more open to opportunities for advancement.
      Epidemiologic research on the relationship of internal-external locus of control
      to mental disorder has generally found that being internal has positive mental
      health effects; while having an external orientation is detrimental. This paper
      addresses these issues by demonstrating that the psychiatric-epidemiologic and
      the race-consciousness literatures lead to opposite predictions about the
      relationship of external attributions (fatalism and system blame) to mental
      health. The article concludes with a series of issues that need to be addressed
      in order to advance knowledge about social and psychological risk factors for
      psychiatric disorders in African Americans.

PMID- 8882846
TI  - Social identity and arterial blood pressure in the African-American community.
AB  - It has been suggested that racism may account in part for health inequalities
      between African Americans and other ethnic groups in the United States. While
      there is a strong plausibility to this suggestion, specifying the causal pathways
      through which enduring patterns of prejudice and discrimination affect
      pathophysiologic processes has proven difficult. The aim of this paper is to
      suggest just such a specification of this effect, building on prior work locating
      this process in social interaction. It is argued that, in mundane social
      interaction, African-American ethnicity as a status attribute overrides the other
      social attributes through which individuals structure the social identities that
      mediate mundane social interaction. Three specific variables that influence
      social identity are examined: lifestyle incongruity, stressful life events, and
      identity accumulation. Using data collected in an African-American community in
      the rural South, it was found that these three variables are related to blood
      pressure in interaction with socioeconomic status. Additionally, each of the
      three variables is related to individuals' perceptions of racism in mundane
      interactions. This pattern of results suggests that the attribution of lower
      social status to African-American ethnicity within the color-conscious society of
      the U.S., and the subsequent effect of this attribution on social interaction, in
      part account for observed health inequalities.

PMID- 8882847
TI  - Hemodynamic responses associated with post-exercise hypotension in normotensive
      black males.
AB  - The purpose of this study was to characterize the hemodynamic responses during
      recovery from moderate intensity exercise in young black normotensive males.
      Nineteen normotensive men (age 25.0 +/- 1.0 yrs, VO2peak 48.8 +/- 1.5 ml.kg-1.min
      1) walked continuously on a treadmill for 40 minutes at 50-60% heart rate
      reserve. Following exercise, blood pressure (by auscultation) and hemodynamic
      variables (impedance cardiography) were monitored for two hours in a quiet room
      with subjects in a seated posture. During the initial 40 minutes of recovery,
      cardiac output, (Q) was significantly greater than the pre-exercise baseline (p <
      0.05). This was mediated by heart rate, which was elevated above the pre-exercise
      baseline for 75 minutes. Mean systolic blood pressure (SBP) was reduced by at
      least 7 mm Hg from 30 minutes to 2 hours post-exercise, compared to the pre
      exercise baseline, (mean = 112 +/- 1.6) (p < 0.05). Total peripheral resistance
      (TPR, dyne.s.cm-5) was depressed for 60 minutes compared to the pre-exercise
      baseline (BL, 959.8 +/- 40.6), p < 0.05, but was fully recovered by two hours. It
      was concluded that in this group of young black normotensive males, moderate
      intensity aerobic exercise led to a prolonged reduction in SBP through relative
      changes in Q and TPR. These observations have not been consistently observed by
      other investigators in normotensive white males under similar experimental
      conditions.

PMID- 8882848
TI  - American Society of Hypertension. Eleventh scientific meeting, May 15-18, 1996.
      Abstracts.

PMID- 8882849
TI  - 1996 Joint Meeting of the Research Society on Alcoholism and the International
      Society for Biomedical Research on Alcoholism. Washington, D.C., June 22-27,
      1996. Abstracts.

PMID- 8882851
TI  - [26th annual meeting of the Austrian Society for Internal Medicine. September 21
      23, 1995. Abstracts].

PMID- 8882850
TI  - VIth International Symposium on Insulin Receptors and Insulin Action, Molecular
      and Clinical Aspects. Copenhagen, Denmark, May 6-10, 1996. Abstracts.

PMID- 8882852
TI  - Society for the Study of Reproduction 29th annual meeting. London, Ontario,
      Canada, July 27-30, 1996. Abstracts.

PMID- 8882853
TI  - Irish Society of Gastroenterology winter meeting. Dublin, 17-18 November 1995.
      Abstracts.

PMID- 8882855
TI  - 80th meeting of the German Society of Pathology. Dresden, Germany, 27 May-1 June
      1996. Abstracts.

PMID- 8882854
TI  - Swiss Society of Traumatology and Insurance Medicine, 2nd Central European
      Congress of Traumatology. Davos May 29-June 1, 1996. Abstracts.

PMID- 8882856
TI  - Conference of European Comparative Endocrinologists from Molecular to Ingrative
      Biology. Rouen, France, September 10-14, 1996. Abstracts.

PMID- 8882857
TI  - A new method to measure alveolar-epithelium permeability in intact lung.

PMID- 8882858
TI  - Counting charges.

PMID- 8882859
TI  - Transalveolar osmotic and diffusional water permeability in intact mouse lung
      measured by a novel surface fluorescence method.
AB  - A surface fluorescence method was developed to measure transalveolar transport of
      water, protons, and solutes in intact perfused lungs. Lungs from c57 mice were
      removed and perfused via the pulmonary artery (approximately 2 ml/min). The
      airspace was filled via the trachea with physiological saline containing a
      membrane-impermeant fluorescent indicator (FITC-dextran or aminonapthalene
      trisulfonic acid, ANTS). Because fluorescence is detected only near the lung
      surface due to light absorption by lung tissue, the surface fluorescence signal
      is directly proportional to indicator concentration. Confocal microscopy
      confirmed that the fluorescence signal arises from fluorophores in alveoli just
      beneath the pleural surface. Osmotic water permeability (Pf) was measured from
      the time course of intraalveolar FITC-dextran fluorescence in response to changes
      in perfusate osmolality. Transalveolar Pf was 0.017 +/- 0.001 cm/s at 23 degrees
      C, independent of the solute used to induce osmosis (sucrose, NaCl, urea),
      independent of osmotic gradient size and direction, weakly temperature dependent
      (Arrhenius activation energy 5.3 kcal/mol) and inhibited by HgCl2. Pf was not
      affected by cAMP activation but was decreased by 43% in lung exposed to hyperoxia
      for 5 d. Diffusional water permeability (Pd) and Pf were measured in the same
      lung from intraalveolar ANTS fluorescence, which increased by 1.8-fold upon
      addition of 50% D2O to the perfusate, Pd was 1.3 x 10(-5) cm/s at 23 degrees C.
      Transalveolar proton transport was measured from FITC-dextran fluorescence upon
      switching perfusate pH between 7.4 and 5.6; alveolar pH half-equilibrated in 1.9
      and 1.0 min without and with HCO3-, respectively. These results indicate high
      transalveolar water permeability in mouse lung, implicating the involvement of
      molecular water channels, and establish a quantitative surface fluorescence
      method to measure water and solute permeabilities in intact lung.

PMID- 8882860
TI  - Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels.
AB  - In voltage-dependent ion channels, the gating of the channels is determined by
      the movement of the voltage sensor. This movement reflects the rearrangement of
      the protein in response to a voltage stimulus, and it can be thought of as a net
      displacement of elementary charges (e0) through the membrane (z: effective number
      of elementary charges). In this paper, we measured z in Shaker IR (inactivation
      removed) K+ channels, neuronal alpha 1E and alpha 1A, and cardiac alpha 1C Ca2+
      channels using two methods: (a) limiting slope analysis of the conductance
      voltage relationship and (b) variance analysis, to evaluate the number of active
      channels in a patch, combined with the measurement of charge movement in the same
      patch. We found that in Shaker IR K+ channels the two methods agreed with a z
      congruent to 13. This suggests that all the channels that gate can open and that
      all the measured charge is coupled to pore opening in a strictly sequential
      kinetic model. For all Ca2+ channels the limiting slope method gave consistent
      results regardless of the presence or type of beta subunit tested (z = 8.6).
      However, as seen with alpha 1E, the variance analysis gave different results
      depending on the beta subunit used. alpha 1E and alpha 1E beta 1a gave higher z
      values (z = 14.77 and z = 15.13 respectively) than alpha 1E beta 2a (z = 9.50,
      which is similar to the limiting slope results). Both the beta 1a and beta 2a
      subunits, coexpressed with alpha 1E Ca2+ channels facilitated channel opening by
      shifting the activation curve to more negative potentials, but only the beta 2a
      subunit increased the maximum open probability. The higher z using variance
      analysis in alpha 1E and alpha 1E beta 1a can be explained by a set of charges
      not coupled to pore opening. This set of charges moves in transitions leading to
      nulls thus not contributing to the ionic current fluctuations but eliciting
      gating currents. Coexpression of the beta 2a subunit would minimize the fraction
      of nulls leading to the correct estimation of the number of channels and z.

PMID- 8882861
TI  - Activation of different Cl currents in Xenopus oocytes by Ca liberated from
      stores and by capacitative Ca influx.
AB  - Xenopus oocytes are an excellent model system for studying Ca signaling. The
      purpose of this study was to characterize in detail the Ca-activated Cl currents
      evoked by injection of inositol 1,4,5-trisphosphate (IP3) into Xenopus oocytes
      voltage-clamped with two microelectrodes. Injection of IP3 into Xenopus oocytes
      activates two different Ca-activated Cl currents. ICl-1 is stimulated rapidly
      (within 5 s after IP3 injection), exhibits time-dependent activation upon
      depolarization, a linear instantaneous IV relationship with a reversal potential
      near ECl, and a curvilinear activation curve with an approximate half-maximal
      activation voltage of > 200 mV. ICl-2D is stimulated slowly after IP3 injection
      (half-maximal stimulation occurs approximately 3 min after injection). ICl-2D has
      a strongly outwardly rectifying instantaneous IV relationship with a reversal
      potential near ECl and is activated by hyperpolarization with a half-maximal
      activation voltage of -105 mV. ICl-2D cannot be activated by Ca released from
      stores but is activated by Ca influx. In contrast, ICl-1 can be stimulated by Ca
      released from intracellular Ca stores. It can also be stimulated by Ca influx
      through store-operated channels if the Ca driving force is increased by a
      hyperpolarization immediately before the depolarization that gates ICl-1
      channels. The description of two currents activated by influx and Ca release from
      stores provides new insights into and questions about the regulation of Ca in
      Xenopus oocytes.

PMID- 8882862
TI  - Cell swelling activates ATP-dependent voltage-gated chloride channels in M-1
      mouse cortical collecting duct cells.
AB  - In the present study we used whole-cell patch clamp recordings to investigate
      swelling-activated Cl-currents (ICl-swell) in M-1 mouse cortical collecting duct
      (CCD) cells. Hypotonic cell swelling reversibly increased the whole-cell Cl-
      conductance by about 30-fold. The I-V relationship was outwardly-rectifying and
      ICl-swell displayed a characteristic voltage-dependence with relatively fast
      inactivation upon large depolarizing and slow activation upon hyperpolarizing
      voltage steps. Reversal potential measurements revealed a selectivity sequence
      SCN- > I- > Br- > Cl- > > gluconate. ICl-swell was inhibited by tamoxifen, NPPB
      (5-nitro-2(3-phenylpropylamino)-benzoate), DIDS (4,4'-diisothiocyanostilbene-2,2'
      disulphonic acid), flufenamic acid, niflumic acid, and glibenclamide, in
      descending order of potency. Extracellular cAMP had no significant effect. ICl
      swell was Ca2+ independent, but current activation depended on the presence of a
      high-energy gamma-phosphate group from intracellular ATP or ATP gamma S.
      Moreover, it depended on the presence of intracellular Mg2+ and was inhibited by
      staurosporine, which indicates that a phosphorylation step is involved in channel
      activation. Increasing the cytosolic Ca2+ concentration by using ionomycin
      stimulated Cl- currents with a voltage dependence different from that of ICl
      swell. Analysis of whole-cell current records during early onset of ICl-swell and
      during final recovery revealed discontinuous step-like changes of the whole-cell
      current level which were not observed under nonswelling conditions. A single
      channel I-V curve constructed using the smallest resolvable current transitions
      detected at various holding potentials and revealed a slope conductance of 55,
      15, and 8 pS at +120, 0, and -120 mV, respectively. The larger current steps
      observed in these recordings had about 2, 3, or 4 times the size of the putative
      single-channel current amplitude, suggesting a coordinated gating of several
      individual channels or channel subunits. In conclusion we have functionally
      characterized ICl-swell in M-1 CCD cells and have identified the underlying
      single channels in whole-cell current recordings.

PMID- 8882863
TI  - N-type inactivation and the S4-S5 region of the Shaker K+ channel.
AB  - The intracellular segment of the Shaker K+ channel between transmembrane domains
      S4 and S5 has been proposed to form at least part of the receptor for the
      tethered N-type inactivation "ball." We used the approach of cysteine
      substitution mutagenesis and chemical modification to test the importance of this
      region in N-type inactivation. We studied N-type inactivation or the block by a
      soluble inactivation peptide ("ball peptide") before and after chemical
      modification by methanethiosulfonate reagents. Particularly at position 391,
      chemical modification altered specifically the kinetics of ball peptide binding
      without altering other biophysical properties of the channel. Results with
      reagents that attach different charged groups at 391 C suggested that there are
      both electrostatic and steric interactions between this site and the ball
      peptide. These findings identify this site to be in or near the receptor site for
      the inactivation ball. At many of the other positions studied, modification
      noticeably inhibited channel current. The accessible cysteines varied in the
      state-dependence of their modification, with five- to tenfold changes in
      reactions rate depending on the gating state of the channel.

PMID- 8882865
TI  - Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle.
      Multiple pathways of channel gating.
AB  - Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles
      in excitation-contraction coupling in skeletal muscle: (a) they function as the
      voltage sensor which undergoes fast transition to control release of calcium from
      sarcoplasmic reticulum, and (b) they provide the conducting unit of a slowly
      activating L-type calcium channel. To understand this dual function of the DHP
      receptor, we studied the effect of depolarizing conditioning pulse on the
      activation kinetics of the skeletal muscle DHP-sensitive calcium channels
      reconstituted into lipid bilayer membranes. Activation of the incorporated
      calcium channel was imposed by depolarizing test pulses from a holding potential
      of -80 mV. The gating kinetics of the channel was studied with ensemble averages
      of repeated episodes. Based on a first latency analysis, two distinct classes of
      channel openings occurred after depolarization: most had delayed latencies,
      distributed with a mode of 70 ms (slow gating); a small number of openings had
      short first latencies, < 12 ms (fast gating). A depolarizing conditioning pulse
      to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant
      increase in the activation rate of the ensemble averaged-current; the time
      constant of activation went from tau m = 110 ms (reference) to tau m = 45 ms
      after conditioning. This enhanced activation by the conditioning pulse was due to
      the increase in frequency of fast open events, which was a steep function of the
      intermediate voltage and the interval between the conditioning pulse and the test
      pulse. Additional analysis demonstrated that fast gating is the property of the
      same individual channels that normally gate slowly and that the channels adopt
      this property after a sojourn in the open state. The rapid secondary activation
      seen after depolarizing prepulses is not compatible with a linear activation
      model for the calcium channel, but is highly consistent with a cyclical model. A
      six-state cyclical model is proposed for the DHP-sensitive Ca channel, which
      pictures the normal pathway of activation of the calcium channel as two voltage
      dependent steps in sequence, plus a voltage-independent step which is rate
      limiting. The model reproduced well the fast and slow gating models of the
      calcium channel, and the effects of conditioning pulses. It is possible that the
      voltage-sensitive gating transitions of the DHP receptor, which occur early in
      the calcium channel activation sequence, could underlie the role of the voltage
      sensor and yield the rapid excitation-contraction coupling in skeletal muscle,
      through either electrostatic or allosteric linkage to the ryanodine
      receptors/calcium release channels.

PMID- 8882864
TI  - Molecular identification of SqKv1A. A candidate for the delayed rectifier K
      channel in squid giant axon.
AB  - We have cloned the cDNA for a squid Kvl potassium channel (SqKv1A). SqKv1A mRNA
      is selectively expressed in giant fiber lobe (GFL) neurons, the somata of the
      giant axons. Western blots detect two forms of SqKv1A in both GFL neuron and
      giant axon samples. Functional properties of SqKv1A currents expressed in Xenopus
      oocytes are very similar to macroscopic currents in GFL neurons and giant axons.
      Macroscopic K currents in GFL neuron cell bodies, giant axons, and in Xenopus
      oocytes expressing SqKv1A, activate rapidly and inactivate incompletely over a
      time course of several hundred ms. Oocytes injected with SqKv1A cRNA express
      channels of two conductance classes, estimated to be 13 and 20 pS in an internal
      solution containing 470 mM K. SqKv1A is thus a good candidate for the "20 pS" K
      channel that accounts for the majority of rapidly activating K conductance in
      both GFL neuron cell bodies and the giant axon.

PMID- 8882866
TI  - Localization of the gene (or genes) for a syndrome with X-linked mental
      retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal
      course in early childhood.
AB  - Linkage analysis is described in a family with X-linked mental retardation,
      ataxia, weakness, floppiness, delayed motor development, absence of deep tendon
      reflexes, hearing impairment and loss of vision (MIM no. 301835). The disease has
      a fatal course due to the susceptibility of the patients to infections,
      especially of the respiratory tract. Clinical signs indicate impairment of the
      posterior columns, peripheral motor and sensory neurons and the second and eighth
      cranial nerves and/or their nuclei. The involvement of the posterior columns of
      the spinal cord is further suggested by the almost complete absence of myelinated
      fibers therein. We localized the responsible gene(s) to Xq21.33-q24 between
      DXS1231 and DXS1001 with a maximum lod score of 6.97. The proteolipid protein
      gene, which codes for two myelin proteins of the central nervous system and is
      located in this region, was considered as a candidate gene for this disorder.
      However, no mutations were found in the protein-coding part of this gene.

PMID- 8882867
TI  - Dombrock blood group (DO): assignment to chromosome 12p.
AB  - The Dombrock blood group system (DO) is a common polymorphism in Caucasians,
      represented by two red cell antigen alleles. In a linkage study in our family
      material of 832 families from the Copenhagen area, we found a strong indication
      of tight linkage with the two flanking DNA polymorphisms D12S358 (z = 7.66; at
      theta M = 0.001, theta F = 0.031) and D12S364 (z = 8.53; at theta M = 0.068,
      theta F = 0.031). DO is assigned to the region 12p13.2-12p12.1 by physically
      localised markers.

PMID- 8882868
TI  - Sequence variations in the Fanconi anaemia gene, FAC: pathogenicity of 1806insA
      and R548X and recognition of D195V as a polymorphic variant.
AB  - Fanconi anaemia (FA) is a rare autosomal recessive disorder associated with
      diverse clinical symptoms, increased chromosomal instability and a marked
      hypersensitivity to crosslinking agents. At least five complementation groups
      have been defined, the gene for group C (FAC) being the only FA gene cloned thus
      far. Several sequence variations have been detected in FA patients, whose
      assignment to group C, however, had not been ascertained by complementation
      studies. Using a functional assay, in which we tested the capacity of a variant
      sequence to correct the defect in FA-C lymphoblasts, we provide evidence for the
      pathogenic status of 1806insA and R548X and for non-pathogenicity of D195V.

PMID- 8882869
TI  - Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal
      muscular atrophy.
AB  - Two genes are known to be involved in spinal muscular atrophy (SMA), namely, SMN
      (survival motor neuron) and NAIP (neuronal apoptosis inhibitory protein).
      Deletion analysis of these genes has been reported for many ethnic groups. We
      have extended this analysis to include 15 Arabic patients (11 unrelated cases of
      type I, which represent practically all of the patients diagnosed within the last
      2 years in Kuwait, and 4 type-II cases from a single kinship). Also, 41 healthy
      relatives (parents and sibs) and 44 control individuals of Arabic origin were
      analyzed. The homozygous deletions of exons 7 and 8 of the SMN gene were found in
      all SMA patients studied. Exon 5 of NAIP was homozygously absent in all type-I
      patients, but was retained in type-II cases. Among members of SMA families, one
      mother was found to be homozygously deleted for NAIP. All of the control
      individuals had both normal SMN and NAIP. Our results are in agreement with the
      general consensus that the incidence of NAIP deletion is higher in the more
      severe SMA cases. Furthermore, they suggest that SMA type-I chromosomes, with the
      dual deletion of the SMN and NAIP genes, are more common in Arabs than in
      patients of other ethnic origin.

PMID- 8882870
TI  - Multiple products in the protein truncation test due to alternative splicing in
      the adenomatous polyposis coli (APC) gene.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR)-based analyses of the
      adenomatous polyposis coli (APC) gene encompassing exons 1-15 revealed a complex
      pattern of products that were due to alternative splicing of exons 9, 10A and 14.
      The multiplicity of polypeptide chains obtained from T7-promoter-directed in
      vitro translation of the RT-PCR product pool was confirmed immunochemically to
      correspond to the mRNA isoforms, but not to represent products of internal
      initiation of translation. This observation is of particular relevance for the
      diagnostic protein truncation test (PTT), since this assay will pick up mRNA
      variants derived from physiological splice events, e.g., skipping of exons 9, 10A
      and 14. In vitro-translated proteins of reduced molecular weight were therefore
      detectable in healthy individuals. We extended this observation to the PTT of
      cDNA encompassing APC exons 1-14 of familial adenomatous polyposis patients.
      Knowledge of the normal polypeptide pattern seen in the diagnostic in vitro
      translation assay allowed us not only to identify translational stop mutations,
      but even to detect a splice acceptor mutation of exon 14 as a result of
      quantitative changes of the isoform pattern. Western immuno blot analysis on
      protein extracts of Epstein-Barr virus-immortalized lymphocytes of the same
      patients revealed that mutations accessible to the RT-PCR PTT yield
      intracellularly undetectable APC proteins.

PMID- 8882871
TI  - Identification of NF2 germ-line mutations and comparison with neurofibromatosis 2
      phenotypes.
AB  - Neurofibromatosis 2 (NF2) is an autosomal inherited disorder that predisposes
      carriers to nervous system tumors. To examine genotype-phenotype correlations in
      NF2, we performed mutation analyses and gadolinium-enhanced magnetic resonance
      imaging of the head and full spine in 59 unrelated NF2 patients. In patients with
      vestibular schwannomas (VSs) or identified NF2 mutations, the mild phenotype was
      defined as < 2 other intracranial tumors and < or = 4 spinal tumors, and the
      severe phenotype as either > or = 2 other intracranial tumors of > 4 spinal
      tumors. Nineteen mutations were found in 20 (34%) of the patients and were
      distributed in 12 of the 17 exons of the NF2 gene, including intron-exon
      boundaries. Seven mutations were frameshift, six were nonsense, four were splice
      site, two were missense, and one was a 3-bp in frame deletion. The nonsense
      mutations included one codon 57 and two codon 262 C-->T transition in CpG
      dinucleotides. The frameshift and nonsense NF2 mutations occurred primarily in
      patients with severe phenotypes. The two missense mutations occurred in patients
      with mild phenotypes, and three of the four splice site mutations occurred in
      families with both mild and severe phenotypes. Truncating NF2 mutations are
      usually associated with severe phenotypes, but the association of some mutations
      with mild and severe phenotypes indicates that NF2 expression is influenced by
      stochastic, epigenetic, or environmental factors.

PMID- 8882872
TI  - Absence of somatic mosaicism in 17 families with hemophilia B: an analysis with a
      sensitivity 10- to 1000-fold greater than that of sequencing gels.
AB  - Most estimates of germ-line mosaicism have been derived from families in which
      there has been transmission of a mutated allele to two or more children by an
      unaffected individual. Previously, analyses for somatic mosaicism detected five
      such individuals by PCR-based sequencing and haplotype analysis at a sensitivity
      of approximately 1 mutant per 10 wild-type alleles. To determine whether
      mutations that occur later in embryogenesis also give rise to somatic mosaicism,
      we analyzed leukocyte DNA from 17 individuals in whom a mutation in the factor IX
      gene was known to have originated. Methods capable of detecting 1 mutant allele
      in 100-10,000 were utilized, and no further examples of somatic mosaicism were
      detected. If confirmed by future studies, the paucity of somatic mosaicism with
      mutant:wild-type allele frequencies ranging from 1:10 to 1:1000 (relative to the
      11% of somatic mosaicism detected with mutant:wild-type allele frequencies of 1:1
      to 1:10) may reflect a higher mutation rate and/or germ-line lineage allocation
      very early in embryogenesis.

PMID- 8882873
TI  - The apolipoprotein E polymorphism in Greenland Inuit in its global perspective.
AB  - Apolipoprotein E (apoE) genotypes were determined in Inuit population samples
      from Nuuk on the south-west coast of Greenland (n = 100) and from the Ammassalik
      region on the south-east coast (n = 78). The epsilon 2 allele was absent in the
      latter sample, and the epsilon 4 allele frequency was relatively high, about 23%.
      As in most other populations, mean plasma lipoprotein-related variables, except
      high-density lipoprotein (HDL) cholesterol, were higher in both Inuit men and
      women with epsilon 4 than in epsilon 3 epsilon 3 genotypes (P < 0.05 for
      triglycerides in men, and for non-HDL cholesterol and apolipoprotein B in women).
      The estimated apoE allele frequencies were combined with data from other studies
      of aboriginal peoples to outline a world map of apoE allele frequencies. A recent
      study of non-human primates suggests that epsilon 4, and not epsilon 3, is the
      ancestral allele in humans and we have used the map to generate additional
      hypotheses regarding the history of the apoE polymorphism in humans.

PMID- 8882874
TI  - HindIII DNA polymorphism in the lipoprotein lipase gene and plasma lipid
      phenotypes and carotid artery atherosclerosis.
AB  - Lipoprotein lipase (LPL) is the rate limiting enzyme in the hydrolysis of core
      triglyceride in chylomicron and very low density lipoprotein (VLDL) thus
      affecting a broad spectrum of plasma lipid levels. In this paper, we investigated
      the association of a HindIII polymorphism in the LPL gene with plasma lipid
      levels and carotid artery wall thickness measured by B-mode ultrasonography. A
      total of 238 Caucasian subjects were selected from the Atherosclerosis Risk In
      Community (ARIC) study (male = 1.31, female = 107) based on their fasting
      triglyceride and LDL-cholesterol levels: normolipidemic (n = 48),
      hypertriglyceridemic (n = 44), hypercholesterolemic (n = 36), and
      hypertriglyceridemic-hypercholesterolemic (n = 110) groups. We observed a
      marginally significant association between lipid phenotypes and HindIII genotypes
      (P = 0.04) in males, with the hypertriglyceridemic and hypercholesterolemic
      groups having a higher frequency (0.65) of the H+H+ genotype than the other two
      groups (pooled: 0.55). In males, there was also a significant association between
      HindIII genotypes and carotid artery wall thickness after considering the effects
      of age, body mass index, cigarette smoking, lipid phenotype and diabetes status
      (P = 0.013), with the H+H+ genotype having a higher average value of carotid
      artery wall thickness (0.84 +/- 0.15 mm) than the other two genotype groups (0.76
      +/- 0.14 mm in H+H(+)-genotype class, 0.75 +/- 0.13 mm in H-H- genotype class).
      In females, no significant associations among LPL HindIII genotype, lipid
      phenotype and carotid artery wall thickness were observed. These results suggest
      that the LPL HindIII polymorphism influences LPL-catalyzed, triglyceride-rich
      lipoprotein metabolism and carotid artery atherosclerosis in a gender-specific
      manner.

PMID- 8882875
TI  - Hypertriglyceridemia and the apolipoprotein CIII gene locus: lack of association
      with the variant insulin response element in Italian school children.
AB  - Hypertriglyceridemia is a common metabolic disorder with a major inherited
      component. In some individuals the condition is suspected to occur as a result of
      overproduction of apolipoprotein (apo)CIII, a major constituent of triglyceride
      rich lipoproteins. Population studies have established an association with the
      apoCIII gene but the identify of the causal mutation remains unknown. In the
      present study we have examined a series of six 5' polymorphic nucleotides (G-935
      to A, C-641 to A, G-630 to A, deletion of T-625, C-482 to T, and T-455 to C) that
      lie within the promoter region of the apoCIII gene for evidence of possible
      involvement in disease susceptibility. The polymorphic nucleotides at positions 
      455 and -482 reside within a negative insulin-response element. We show, in a
      community-based sample of 503 school children, that a DNA polymorphism (S2
      allele) within the 3'-noncoding region of the apoCIII gene was associated with
      elevated apoCIII and triglyceride levels, but that the polymorphic nucleotides of
      the promoter were not. In addition, no obvious effect of any extended apoCIII
      promoter haplotype on plasma apoCIII or triglyceride levels, over and above that
      conferred by the presence of the S2 polymorphic nucleotide, was detected. These
      results demonstrate that none of the 5' apoCIII polymorphisms can account for the
      association of the apoCIII gene locus with hypertriglyceridemia and, moreover,
      owing to linkage disequilibrium, raise the possibility that the region conferring
      susceptibility maps downstream, rather than upstream, of the apoCIII gene
      promoter sequences.

PMID- 8882876
TI  - Age-dependent penetrance and mapping of the locus for juvenile and early-onset
      open-angle glaucoma on chromosome 1q (GLC1A) in a French family.
AB  - The GLC1A locus for autosomal dominant primary open-angle glaucoma (POAG) with
      juvenile onset (before 20 years) has been mapped to chromosome 1q21-q31.
      Recently, a French-Canadian family was described in which both juvenile-onset and
      middle-age or early-onset POAG were observed and linked to GLC1A. We now describe
      a second POAG family with variable age of onset (range 11-51, median 36 years of
      age). Linkage to GLC1A was established with a maximum lod score of 6.21 at the
      D1S452 locus. A recombination event in a severely glaucomatous patient restricted
      the distal boundary of the GLC1A interval proximal to the AFM154xc9 marker. This
      study strengthens the idea that early-onset POAG may also be determined by the
      GLC1A genetic region.

PMID- 8882877
TI  - Exclusion of the MSX1 homeobox gene as the gene for the Ellis van Creveld
      syndrome in the Amish.
AB  - Ellis van Creveld syndrome (EVC) is an autosomal recessive disorder which has
      previously been mapped to human chromosome 4p16.1. This disorder is characterized
      by disproportionate dwarfism, polydactyly, cleft palate, natal teeth, and
      congenital heart disease. The MSX1 homeobox gene also maps to the 4p16.1 region.
      Msx gene transcripts in the mouse embryo are known to be involved in pattern
      formation of the developing limb bud and craniofacial bones. Thus, on the basis
      of both map location and known gene function, MSX1 was an excellent candidate as
      the causative gene for EVC. Nonetheless, direct DNA sequencing of both exons of
      the MSX1 gene in five affected individuals segregating with the EVC phenotype, as
      well as those of two obligate carriers, revealed no mutations in the coding
      region of the gene.

PMID- 8882878
TI  - Molecular cytogenetic characterization of breakpoints involving pericentric
      inversions of human chromosome 9.
AB  - Pericentric inversions involving the secondary constriction (qh) region of
      chromosome 9 are considered to be normal variants. The evolutionary mechanisms
      and conservation of these inversions via Mendelian fashion have been investigated
      since the advent of banding techniques. Routine cytogenetic techniques cannot
      provide the fine characterization necessary to determine the type of genetic
      material involved in these rearrangements. Therefore, the fluorescence in situ
      hybridization technique with the human centromere-specific alpha satellite and
      the beta satellite (D9Z5) and classical satellite (D9Z1) human DNA probes were
      used to identify the breakpoints of chromosome 9 pericentric inversions. Four
      unique types of pericentric inversions involving the 9qh region were observed,
      and the mechanism may be due to breakage and reunion at the proposed breakpoints.
      They are: type A inversions consist of breakpoints within the alpha and beta
      satellite DNA regions; type B consist of breakpoints within the beta satellite
      DNA region and band 9q13; type C involve breakage within the beta and classical
      satellite DNA regions, and type D have breakpoints within the alpha and classical
      satellite DNA regions. Obviously, reshuffling of satellite DNA sequences has
      occurred, which has given rise to a variety of heteromorphisms whose clinical
      significance remains obscure.

PMID- 8882879
TI  - Molecular genetics of familial hypercholesterolemia in Israel.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by a
      multitude of low density lipoprotein receptor (LDL-R) mutations. The purpose of
      the current investigation was to define the spectrum of mutations causing FH in
      Israel and determine their relative distribution among diverse origin groups. A
      total of 193 FH families were recruited in Israel, 54 of them through the MED PED
      (Make Early Diagnosis Prevent Early Death) FH program. Molecular analysis of the
      LDL-R using single-strand conformation polymorphism (SSCP) or denaturing gradient
      gel electrophoresis (DGGE) or both has been completed in 95 index cases. This
      analysis resulted in the identification of 15 LDL receptor mutations, including 7
      novel mutations (del 197, C308G, R385W, splice junction mutation of intron 14,
      del 328, del 502-505, stop 10, del 165), that were present in 49 index cases
      (52%). The 15 mutations are mapped to three known functional domains of the
      receptor (7 in the LDL-binding region, 7 in the epidermal growth factor precursor
      homology region and 1 in the membrane-spanning region). Screening for the
      identified mutations in the remaining 98 index cases enabled the molecular
      diagnosis of 31 additional cases. It is therefore concluded that 80 out of 193
      index cases (41%) harbor 1 of the 15 mutations described here. Three mutations
      del197 (FH-Lithuania), D147H (FH-Sephardic), and stop660 (Lebanese allele)-were
      found in a total of 66 index cases (34%); these may be regarded as founder
      mutations in the three respective origin groups. In conclusion, in Israel
      molecular heterogeneity at the LDL receptor gene locus reflects the ethnic
      distribution of its origin groups. The results of the present investigation
      provide valuable diagnostic tools for a subset of the Israeli patients with FH
      who are at high risk for atherosclerosis and its complications.

PMID- 8882880
TI  - Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in
      patients with congenital nephrogenic diabetes insipidus.
AB  - The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male
      patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R
      gene of the patient of family 1 had the wild-type sequence. Consequently, the
      coding region of the aquaporin-2 gene including the exon-intron junctions was
      sequenced. A novel G to T transversion at codon 202, predictive of an exchange of
      tryptophan 202 by cysteine, was identified. As the mutation occurs at G-1 of the
      5' splice donor site of intron 3, aberrant splicing is also likely. The mutation
      involves one of the supposed water pore-forming loops. Therefore, both aberrant
      splicing and amino acid substitution are likely to result in a functionally
      defective protein. Sequencing of the complete V2R gene of the male patient of
      family 2 revealed a novel single-base deletion at codon 310 (delta C1001),
      shifting the reading frame to give an altered amino acid sequence beginning at
      codon 311. The mutation is unique in predicting a C-terminally extended protein
      (termination after codon 434 in the mutant receptor instead of codon 371 in the
      wild-type). The deduced mutant protein is likely to be nonfunctional since the
      amino acid sequence of the seventh transmembrane domain and the C-terminus is
      altered.

PMID- 8882881
TI  - OB gene not linked to human obesity in Mexican American affected sib pairs from
      Starr County, Texas.
AB  - Obesity is a highly prevalent disease, which is associated with a number of
      chronic conditions and, as such, represents a major public health burden.
      Numerous studies indicate that there is a genetic component contributing to
      interindividual variability in obesity. The discovery of the ob gene in mice,
      mutations in which produce extreme obesity and non-insulin-dependent diabetes
      mellitus (NIDDM), provides a prime candidate gene for human obesity. We
      investigated linkage between the human OB gene and obesity in a sample of Mexican
      Americans from Starr County, Texas. Markers D7S635 and D7S1875, estimated to lie
      within a region approximately 290 to 400 kb proximal to the OB gene, were used to
      genotype 177 obese individuals distributed in 64 sibships. Obesity was defined as
      a body mass index (BMI) above 30 kg/m2. Linkage analyses for affected sibling
      pairs provided no evidence for linkage in this sample. In addition, differences
      between siblings for weight, BMI, systolic and diastolic blood pressure, percent
      body fat, waist-to-hip ratio, and blood lipid measures were not significantly
      related to number of alleles shared identical by state (IBS) for either of the
      two markers. While the OB gene may be involved in the metabolic sequences leading
      to obesity, the present linkage results do not support the existence of common
      genetic variation at or near the OB locus that increases risk for human obesity.

PMID- 8882882
TI  - The origin of the most common mutation of adenine phosphoribosyltransferase among
      Japanese goes back to a prehistoric era.
AB  - The incidence of adenine phosphoribosyltransferase (APRT) deficiency is higher
      among Japanese nationals than among other ethnic groups, and the most common
      mutation (APRT*J, ATG to ACG mutation at codon 136) accounts for 68% of the
      disease-causing genes among Japanese. To investigate the origin of these
      mutations, we studied the geographical distribution of the mutant genes in Japan.
      The APRT*J mutation is distributed nearly uniformly in the four main islands of
      Japan and Okinawa, suggesting a very early origin. The products of PCR
      amplification between positions 2344 and 2750 of the genomic APRT sequence were
      examined by SSCP analysis in random blood samples from Japanese, Korean, and
      Taiwanese nationals. Among 955 random Japanese blood samples, 7 (0.73%) were
      heterozygous for the APRT*J mutation, giving a calculated heterozygote frequency
      of 1.1% among Japanese for the entire APRT deficiency. None of 231 Taiwanese
      samples contained heterozygotes for the APRT*J mutation, while 2 (0.53%) of 356
      Korean samples were heterozygous. In addition to the APRT*J sequence, a total of
      five variant sequences was found. Sequencing one variant revealed a base
      substitution in intron 4, suggesting therefore that they are harmless mutations.
      Since the APRT*J mutation is present in Koreans and Okinawans who share ancestors
      only before the Yayoi era (third century BC to third century AD), the origin of
      the APRT*J mutation predates 300 BC.

PMID- 8882883
TI  - Microsatellite instability and mutations of p53 and TGF-beta RII genes in gastric
      cancer.
AB  - To investigate the molecular mechanism of gastric carcinogenesis, we analyzed
      genetic instability and p53 gene mutations in 40 primary gastric carcinomas.
      Tumor samples were from untreated patients with no family history suggestive of
      genetic predisposition to cancer. We screened six microsatellite loci by the
      polymerase chain reaction (PCR) method, and exons 5-8 of the p53 gene by the PCR
      based denaturing gradient gel electrophoresis and sequencing techniques.
      Microsatellite instability was detected in 32.5% (13/40), and gene mutations in
      40% (16/40), of the tumors analyzed. No statistically significant associations
      were found between genetic alterations and clinico-pathological variables (with
      the exception of diffusion of lymph node metastases, which was inversely
      associated with the presence of microsatellite alterations; P < 0.01).
      Interestingly, a negative association was found between genetic instability and
      p53 gene mutations: 11 out of 13 tumors showing instability proved to carry a
      nonmutated p53 gene versus 2/13 carrying a mutated gene (P = 0.03). These
      observations suggest that genetic instability and p53 gene mutations play a
      crucial role in the gastric carcinogenic process, but likely act through distinct
      pathways during cancer development. However, genetic instability is not in and of
      itself neoplastic. Therefore, we investigated whether insertion/deletion
      mutations of the polyadenine tract within the transforming growth factor-beta
      type II receptor gene (TGF-beta RII) were frequently present in gastric tumors
      with an RER+ (replication error) phenotype. We found RII mutations in 8/40 (20%)
      samples: mutations were present in 7/13 (54%) RER+ tumors versus 1/27 (4%) RER-
      cases (P < 0.001).

PMID- 8882884
TI  - Simultaneous detection of structural and numerical chromosome abnormalities in
      sperm of healthy men by multicolor fluorescence in situ hybridization.
AB  - Both structural and numerical chromosome aberrations in sperm represent important
      categories of paternally transmitted genetic damage. Therefore, a new multiprobe
      fluorescence in situ hybridization (FISH) method, using DNA probes for three
      targets (centromere and telomere of chromosome 1, centromere of chromosome 8),
      was developed to detect human sperm carrying three types of chromosomal defects:
      (1) terminal duplications or deletions in chromosome 1p, (2) aneuploidy involving
      chromosomes 1 or 8, and (3) diploidy. Baseline frequencies were determined for
      three healthy donors who had been previously evaluated for sperm cytogenetics by
      the human-sperm/hamster-oocyte cytogenetic technique (hamster technique). Among
      approximately 120,000 sperm analyzed by the new FISH method, the average baseline
      frequencies of sperm carrying telomeric duplications and deletions of 1p were 3.2
      +/- 1.9 and 2.9 +/- 3.6 per 10(4), respectively. Diploid sperm was found in an
      average frequency of 6.6 +/- 4.0 per 10(4). Average frequencies of disomic sperm
      for chromosomes 1 or 8 were 1.7 +/- 2.2 and 1.9 +/- 2.3 per 10(4), respectively.
      Inter-individual differences were observed for deletions of 1p but not for the
      other sperm phenotypes. A good correlation was obtained between the frequencies
      of sperm with structural chromosome aberrations detected with the new assay and
      the frequency of sperm carrying premeiotic or meiotic cytogenetic damage detected
      with the hamster technique. The observed levels of numerical aberrations with the
      new FISH assay were within range of the baseline frequencies reported by the
      hamster technique. The newly developed FISH assay has promising applications in
      genetic, clinical, physiological and toxicological studies.

PMID- 8882885
TI  - Sequence-specific and length-dependent interaction of C2H2 zinc fingers and (TA)n
      microsatellites.
AB  - A possible function for microsatellite elements still remains elusive. Here we
      demonstrate that (TA)n microsatellites can be recognized in vivo in transient
      assays by a combination of naturally occurring C2H2 zinc fingers with high
      affinity that depends on specific protein-DNA contacts. This interaction results
      in an upregulation of the basal transcription level, when (TA)n elements are
      placed upstream of a minimal promoter. Upregulation depends on the length of the
      element. Our results suggest that specific interaction of transcription factors
      with microsatellite sequences may underlie effects on transcriptional regulation
      exerted by these sequences. Identification of such interactions would be a first
      step towards understanding the function and evolution of microsatellite elements.

PMID- 8882887
TI  - Twelve amplified and expressed genes localized in a single domain in glioma.
AB  - Gene amplification has been associated both with tumor stage and progression in
      human gliomas. Several distinct amplified loci have been identified by
      comparative genomic hybridization and Southern blot analysis. It has been
      increasingly recognized that amplified domains comprise multiple genes. Here, we
      demonstrate amplification of up to 12 different genes from an amplified domain at
      12q13-15 that has been found in approximately 15% of astrocytomas and
      glioblastomas. The amplified genes were GLI, WNT1, MDM2, SAS, CDK4 OS-4, GAS16,
      GAS27, GAS41, GAS56, GAS 64 and GAS89. In one glioblastoma all 12 amplified genes
      were also found to be expressed. These results strongly warrant the search for as
      yet unidentified genes in regions previously reported to be amplified.

PMID- 8882886
TI  - Linkage disequilibrium analysis in Machado-Joseph disease patients of different
      ethnic origins.
AB  - Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar
      degeneration originally described in families of Portuguese-Azorean ancestry. The
      hypothesis that its present world distribution could result from the spread of an
      original founder mutation has been raised. To test this possibility we have
      conducted a linkage disequilibrium study of markers segregating with the MJD1
      locus in a total of 64 unrelated families of different geographical origins.
      Significant association was detected between the MJD1 locus and marker alleles at
      loci D14S280, D14S1050 and D14S81. All affected individuals, except one Chinese
      family, had allele 3 (237 bp) at D14S280. This finding is consistent with a
      founder effect in our MJD population. However, distinct haplotypes were observed
      in patients originating from the two Azorean islands showing the highest disease
      prevalence; therefore, the possible existence of more than one founder mutation
      can not be excluded with the markers currently available.

PMID- 8882888
TI  - Human Gene Mutation Database.

PMID- 8882890
TI  - Sparfloxacin worldwide in vitro literature: isolate data available through 1994.
AB  - Sparfloxacin is a piperazinyl, cyclopropyl-fluoroquinolone with broad-spectrum
      antibacterial activity. Compared to other quinolones, sparfloxacin displays
      improved activity against a variety of pathogens including Staphylococcus,
      Streptococcus, Enterococcus, Chlamydia, Mycoplasma, Ureaplasma, and Mycobacteria
      species. Other susceptible organism group include Haemophilus, Legionella,
      Moraxella, Neisseria, Aeromonas, Acinetobacter, Bordetella, Brucella,
      Campylobacter, Gardnerella, and Helicobacter species. Most Enterobacteriaceae are
      also susceptible, whereas most isolates of Pseudomonas aeruginosa are not.
      Sparfloxacin is bactericidal. Activity is generally stable to variations of
      inoculum, pH, and cation concentration, and it is unchanged in the presence of 5%
      sodium cholate or 70% human serum. Susceptibility to the drug is diminished in
      urine. Cross-resistance, although incomplete, has been documented with other
      quinolones, but not with other antimicrobic classes.

PMID- 8882891
TI  - Use of the in vitro induced antibody production test (IVIAP) to elucidate
      inconclusive status of HIV-1 infection.
AB  - Studies have demonstrated the diagnostic usefulness of in vitro production of
      virus-specific antibodies by peripheral blood mononuclear cells (PMBC) from HIV
      infected subjects. We evaluated the IVIAP (in vitro induced antibody production)
      by lympocytes from peripheral blood of 30 adult patients. Samples included 10
      patients with inconclusive status of HIV-1 infection on previous serologic
      screening (2 blood donors, 8 with high risk behavior), 10 AIDS patients (CDC II
      IV), and 10 known seronegative subjects. Positive IVIAP results were obtained on
      2 of 10 inconclusive cases, earlier than seroconversion would demonstrate. The 8
      remaining cases resulted in a negative outcome on IVIAP test, even in 2
      seronegative homosexuals presenting Kaposi's sarcoma. Results showed 100%
      concordance either with a clinical/serological follow-up done after IVIAP tests
      or PCR performed for Kaposi's cases. Also, no false-positive or false-negative
      was detected on control groups. We concluded that IVIAP could identify the real
      status of HIV infection in a shorter time and with low cost compared to
      conventional serological methods currently available. The IVIAP test is easily
      performed so that can be considered as a routine supplemental test.

PMID- 8882892
TI  - Evaluation of the mycobacteria growth indicator tube compared to Septi-Chek AFB
      for the detection of mycobacteria.
AB  - The Mycobacteria Growth Indicator Tube (MGIT) and the AFB Septi-Check (SC)
      systems were compared for the ability to detect myobacterial isolates, time to
      detection, and rate of bacterial contamination. Fifty-eight mycobacterial culture
      positive specimens were studied. MGIT and SC were both positive in 30 of the 58
      specimens (52%); SC alone was positive in 22 (38%), and MGIT alone was positive
      in 6 (10%) of the 58 specimens. Among the 30 isolates identified in both systems,
      there were 7 Mycobacterium tuberculosis, 14 M. avium, 6 M. fortuitum-chelonae
      complex, and 3 other mycobacterial species. MGIT detected Mycobacterium
      tuberculosis faster; SC detected M. avium complex faster and more often; and M.
      fortuitum-chelonae isolates were detected at the same rate. MGIT showed more
      contamination (12.6%) than did the SC (7.8%). MGIT is comparable to SC for the
      detection of MTB, but MAC isolates were detected more often and faster in the SC
      system.

PMID- 8882893
TI  - Clinical evaluation of a dried commercially-prepared microdilution panel for
      antifungal susceptibility testing.
AB  - A commercially-prepared dried broth microdilution panel (Sensititre) was compared
      with a reference microdilution method for antifungal susceptibility testing of
      two reference yeast strains and 98 clinical isolates of Candida spp. The
      antifungal agents tested include 5-fluorocytosine (5FC), fluconazole,
      itraconazole, and D0870. Microdilution testing was performed according to
      National Committee for Clinical Laboratory Standards (NCCLS) recommendations.
      Minimum inhibitory concentration (MIC) endpoints were read visually after 48
      hours of incubation and were assessed independently for each microdilution panel.
      The MICs for the reference strains were within published control limits for both
      reference and Sensititre microdilution panels. Discrepancies among MIC endpoints
      of no more than two dilutions (two wells) were used to calculate the percent
      agreement. An acceptable level of agreement between Sensititre and reference
      panels was observed for all antifungal agents when tested against the 98 clinical
      isolates. Agreement ranged from 83% for itraconazole to 93% for 5FC. The
      Sensititre dried microdilution panel appears to be a viable alternative to
      inhouse prepared microdilution panels and to the NCCLS microdilution reference
      method.

PMID- 8882894
TI  - DNA macrorestriction profiles and antifungal susceptibility of Candida
      (Torulopsis) glabrata.
AB  - Candida (Torulopsis) glabrata is an emerging nosocomial pathogen that may be
      relatively resistant to fluconazole. A series of 75 isolates (blood, urine,
      tissue, and other sites) from 16 patients (1 to 12 isolates per patient) at a
      single university medical center were analyzed by pulsed field gel
      electrophoresis (PFGE) of restriction endonuclease digests of chromosomal DNA.
      The MICs of the isolates for amphotericin B, flucytosine, fluconazole, and
      itraconazole, were determined by a microdilution broth method. A preliminary
      study of seven restriction enzymes, three producing small fragments (Hinf I, Hind
      III, Eco RI) and four producing large fragments (Eag I, BssH II, Sfi I, Not I)
      identified Not I as giving interpretable banding patterns. Isolates were
      considered of different types if they differed by two or more bands. Sixteen
      distinct DNA types (A to P) were identified. Karyotyping was used an an
      additional technique to compare strains with a common PFGE type. Most patients
      were colonized or infected with a single type at multiple body sites and over
      time. One PFGE type was shared by four patients housed in different areas of the
      institution at different times. For two of these four patients, the karyotype was
      also indistintuishable. Five patients were each colonized with two distinct
      types. The MIC of the strains studied were amphotericin B 0.5-1.0 microgram/ml
      (MIC90 = 1.0 microgram/ ml), 5-fluorocytosine 0.25-->256 micrograms/ml (MIC90 = 2
      micrograms/ml), fluconazole 0.25-->128 micrograms/ml (MIC90 = 32 micrograms/ml),
      and itraconazole 0.06-8.0 micrograms/ml). Molecular typing by PFGE using Not I
      digestion is a useful technique for epidemiological investigation as
      epidemiologically related isolates are generally identical and epidemiologically
      unrelated isolates are different by this method.

PMID- 8882895
TI  - Activity of penicillin and three third-generation cephalosporins against US
      isolates of Streptococcus pneumoniae: a 1995 surveillance study.
AB  - In a surveillance study of Streptococcus pneumoniae from the United States the
      incidence of resistance (including both resistant and relatively resistant
      strains) to penicillin was 37.2% when tested by the oxacillin disk-diffusion
      test, or 27.2% when tested by microdilution minimum inhibitory concentrations.
      Strains that were susceptible to penicillin by the oxacillin test were also
      susceptible to the third-generation cephalosporins cefotaxime, ceftriaxone, and
      ceftizoxime. The overall resistance (without regard to penicillin resistance) to
      cefotaxime was 8.8%, to ceftriaxone was 7.9%, and to ceftizoxime was 17.2%; the
      rates of resistance among penicillin-resistant and relatively resistant strains
      (combined), however, were 23.6% for cefotaxime, 21.4% for ceftriaxone, and 43.2%
      for ceftizoxime. The incidence of penicillin resistance and relative resistance
      in these pneumococcal isolates varied from one institution to another, but all
      institutions had these strains and the incidence varied from 4.3% to 60.9%.
      Having ceftizoxime, the least active of the third-generation cephalosporins,
      tested on the formulary did not appear to increase selection of beta-lactam
      resistant strains. The increased resistance to penicillin with the concomitant
      increase in resistance to third-generation cephalosporins may greatly increase
      the difficulty of selecting optimal therapy of patients with life-threatening
      infections due to S. pneumoniae.

PMID- 8882896
TI  - Penicillium peritonitis in a patient receiving continuous ambulatory peritoneal
      dialysis.
AB  - We describe herein a case of peritonitis caused by Penicillium species in a
      patient receiving continuous ambulatory peritonal dialysis (CAPD). This is the
      first reported case of Penicillium peritonitis complicating CAPD. It is also
      unusual because Penicillium typically is considered a contaminant and only rarely
      is it considered a human pathogen.

PMID- 8882897
TI  - Cholinergic agents structurally related to furtrethonium. 3. Synthesis and
      antimuscarinic activity of a series of N-(5-methyl-2-furfuryl and-tiophenyl)
      dialkyl amines and of 2-dimethylamino methyl-4-(1'-substituted-acetoxy-methyl)
      1,3-dioxolanes.
AB  - The introduction of an homologous series of cyclic amines at position 2 of 5
      methylfurane and its isoster 5-methylthiophene induced a weak antagonist
      behaviour, probably depending on the steric hindrance of the substituents at the
      nitrogen, in the case of the cardiac tissue. Surprisingly, when evaluated on
      guinea-pig ileum preparatons, these compounds showed non-muscarinic effects, not
      related either to nicotinic or istaminergic effects, the nature of which awaits
      to be explained. Substitution of the furane ring on the structure of the lead 2a,
      b, obtained in a previous study, with the bioisoster 1,3-dioxolane moiety gave
      potent but not selective analogues (17 and 18).

PMID- 8882898
TI  - A novel method for boronating antibodies without loss of immunoreactivity, for
      use in neutron capture therapy.
AB  - The search for suitable boron containing compounds for 10B neutron capture
      therapy (BNCT) is based on the principle that boron atoms must be delivered
      specifically to tumour cells at a concentration high enough to be effective
      without being toxic to normal cells. Specificity may be achieved through
      monoclonal antibodies. However, it has been difficult to conjugate large numbers
      of boron atoms to the antibody molecules without inactivating them. We have
      devised a strategy to do this indirectly through the use of a boronated glutamate
      lysine polymer in conjunction with biotin and streptavidin.

PMID- 8882899
TI  - Synthesis and biological evaluation of imidazole based compounds as cytochrome P
      450 inhibitors.
AB  - Several phenyl ethyl and phenyl propyl imidazole based compounds have been
      synthesised and their biological activity evaluated against human placental
      Aromatase (AR), rat testicular 17 alpha-hydroxylase/ 17,20-lyase (P450(17) alpha)
      and bovine cholesterol side chain cleavage (CSCC). The compounds showed good
      selectivity towards AR with N-[2-(4'-Nitrophenyl) ethyl] imidazole (2) (IC50 =
      0.16 +/- 0.01 microM, Ki = 0.09 +/- 0.01 microM), the most potent AR inhibitor,
      showing some 130 times greater potency over Aminoglutethimide (AG) (IC50 = 20.0
      +/- 2.6 microM, Ki = 11.0 +/- 2.0 microM). N-[3-(4'-Fluorophenyl) propyl]
      imidazole (10) (IC50 = 0.31 +/- 0.01 microM, Ki = 0.34 +/- 0.05 microM), N-(2-(4'
      Fluorophenyl ethyl) imidazole (5) (IC50 = 0.74 +/- 0.01 microM, Ki = 0.40 +/-
      0.02 microM), N-(3-(4'-Chlorophenyl propyl) imidazole (9) (IC50 = 0.82 +/- 0.02
      microM) and N-[3-(4'-Nitrophenyl) propyl] imidazole (7) (IC50 = 0.84 +/- 0.02
      microM, Ki = 0.10 microM) were also more potent than AG. Of the compounds tested
      for P450(17) alpha activity, 7 (IC50 = 25.0 +/- 2.0 microM), N-[2-(4'
      Aminophenyl) ethyl] imidazole (3) (IC50 = 27.6 +/- 0.10 microM), 9 (IC50 = 29.0
      +/- 4.0 microM) and 2 (IC50 = 30.2 +/- 2.0 microM) showed the highest activity,
      possessing approximately half the activity of Ketoconazole (IC50 = 12.1 +/- 2.9
      microM). Compounds 1, 2, 3, and 7 showed 0% inhibitory activity towards CSCC at
      200 microM whilst AG showed 83% inhibition under the same conditions. The
      compounds proved themselves to be excellent lead compounds and supported the
      novel models developed by Ahmed for AR and P450(17) alpha.

PMID- 8882900
TI  - Specific interaction between HIV-1 proteinase and 5'-phosphate peptidomimetic
      derivatives of nucleoside analogues.
AB  - HIV-1 proteinase is shown to interact with 5'-(methoxyglycinyl-S-(N
      methylcarbamoylmethyl))thiophosphat e derivatives of 3'-fluoro-3'-deoxythymidine
      (FLT), 3'-azido-3'-deoxythymidine (AZT) and of acyclovir (ACV). The enzyme is
      inhibited in vitro by micromolar concentrations of these compounds. The Ki-value
      for the FLT derivative was 15 microM. Other closely related 5'-phosphate
      derivatives of nucleoside analogues tested showed no effect on the enzymatic
      activity, indicating a high degree of specificity. This type of compound is
      unstable in buffer at alkaline pH and in cell culture resulting in inhibition of
      HIV replication. HIV proteinase does not catalyse the hydrolysis nor is it
      inhibited by the hydrolysis products. Modelling of the non-nucleoside moiety of
      the compounds show that they can adopt a low energy conformation which is similar
      to a pseudo C2 symmetric inhibitor of HIV-1 proteinase.

PMID- 8882901
TI  - Structure and in vivo activity of hypoglycaemic analogues of human growth hormone
      (6-13).
AB  - A range of peptide analogues related to Asu11-human growth hormone (6-13) have
      been synthesized and tested for hypoglycaemic activity using in vivo insulin
      tolerance tests. Utilising an alanine scan procedure and a selective amino acid
      residue approach these structure-activity studies suggest that residues Phe10,
      Arg8 and the C-terminal beta-turn structure are important for the expression of
      biological activity.

PMID- 8882902
TI  - Dopaminergic (4aR,10bS)-cis- and (4aS,10bS)-trans-octahydrobenzo[F]quinolines
      have similar pharmacophores.
AB  - The structures and absolute configurations of two N-phenethyl substituted cis-
      and trans-octahydrobenzo[f]quinolines were determined by X-ray crystallography.
      The absolute configurations of the enantiomers that have high affinity for
      dopaminergic receptors were found to be (4aR,10bS) and (4aS,10bS) for the (-)-cis
      and (-)-trans-8,9-dihydroxy substituted compounds. This is consistent with
      previous results for a dopamine agonist pharmacophore. MM2-87 calculations for a
      cis isomer, which has two alternative chair conformations of the piperidine ring,
      indicated that the preferred conformer is the same as that observed in the
      crystal structure. Superposition of the more active cis and trans enantiomers
      showed that the three dimensional orientations of the phenyl ring and the
      ammonium group are similar in the two geometrical isomers. The cis isomer,
      however, has steric bulk out of the plane of the molecule and this appears to
      result in a loss of agonist efficacy. The addition of the N-phenethyl group to
      the 7-OH and 7,8-diOH cis compounds, however, appears to be sufficient to restore
      high affinity for dopaminergic receptors unlike previously synthesized cis
      compounds. These cis compounds, however, appear to be mixed agonist/antagonists
      or antagonists on functional assays of dopaminergic activity.

PMID- 8882903
TI  - Validity of a random noise oscillation and body box system for the measurement of
      the respiratory impedance of small animals.
AB  - The accuracy and validity of a body box system which was developed for the
      measurement of airway and chest wall impedance in small animals such as canines
      was evaluated. Input impedance was calibrated using a resistance tube and the
      mouth flow sensing system was designed to be as symmetrical as possible such that
      the minimal common mode rejection ratio (CMRR) from 10 to 40 Hz was greater than
      60 dB. The validity of this system using the resistance tube and inertant models
      indicated that the average error ratio for the input impedance and for the flow
      transfer function between the mouth and chest flow was within 3 and 0.5%,
      respectively. The location of the box pressure port near to the oscillatory flow
      inlet was shown to potentially give rise to errors in the measurement of the flow
      transfer factor due to the direct effects of the inflow. A distance of 60 cm was
      adopted in the present system, which proved to be sufficient to avoid this
      effect. It was concluded that the body box system which is described for small
      animals in the present study is appropriate for obtaining separate and accurate
      airway and tissue impedance data.

PMID- 8882904
TI  - Chest flow during the initial inspiratory phase (V0.1) in pulmonary diseased
      patients.
AB  - We measured the chest flow 0.1 s after the onset of the inspiratory phase (V0.1)
      in patients with chronic pulmonary emphysema (CPE: n = 5), interstitial
      pneumonitis (IP: n = 5) and normal subjects (Nor: n = 5). The subjects sat in a
      body box and breathed air from outside of the body box. V0.1 was measured during
      rest and during maximal breathing (V0.1-rest, V0.1-max) and then these results
      were compared with P0.1 (P0.1 rest, P0.1-max) values. V0.1-rest was not
      significantly different between the three groups (Nor: 0.25 +/- 0.10, CPE: 0.27
      +/- 0.06, IP: 0.26 +/- 0.06, l/s), whereas the P0.1-rest in IP patients was
      significantly greater than in normal subjects (Nor: 1.98 +/- 0.61, CPE: 3.00 +/-
      0.80, IP: 3.60 +/- 0.68 hPa; P < 0.05 compared with normal). The V0.1-max in CPE
      and IP patients was significantly lower than in normal subjects (Nor: 3.66 +/-
      1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05 compared with normal
      subjects (Nor: 3.66 +/- 1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05
      compared with normal), whereas P0.1-max in IP patients was not significantly
      different with in normal subjects (Nor: 33.2 +/- 10.2, CPE: 9.8 +/- 3.7, IP: 19.5
      +/- 3.4 hPa, P < 0.05 compared with normal, P < 0.05 compared with CPE). A
      simulation of the influence of the mechanical properties of the respiratory
      system on V0.1 and P0.1 using the Runge-Kutta method suggested that V0.1 was
      negatively affected by airway resistance but positively affected by chest wall
      and lung compliance. In contrast, the influence of respiratory mechanics on P0.1
      was much less than on the V0.1, except for highly decreased lung compliance. In
      CPE patients, it was suspected that mechanical disorders might not simply be the
      determining factors of V0.1-max, but that limitations of the neuro-muscular drive
      due to chest wall deformity may also play a definitive role in the smaller V0.1
      max. In contrast, it may be inferred that IP patients had to exert greater
      inspiratory effort as compared with the other two groups in order to maintain a
      similar V0.1-rest because of the increased airway resistance and decreased tissue
      compliance; thus these abnormal mechanical properties suppress the increase in
      the V0.1-max. It may be concluded that V0.1 is a good index of chest wall
      acceleration, which is determined by both the neuro-muscular drive and the
      mechanics of the respiratory system.

PMID- 8882906
TI  - Indirect measurement of tidal volume by multi-lead electrocardiograms: effect of
      filtering, deep breath, lead and posture.
AB  - We examined a new method for estimating tidal volume from the electrocardiogram
      (ECG) in order to dispense with the need for sensors used exclusively for tidal
      volume measurement. The direction of the vector loop in the QRS complex (DVL) was
      defined as the direction of the diagonal line of the rectangle which
      circumscribed the vector loop obtained from two orthogonal leads. Two leads of
      the ECG were transformed into the orthogonal leads using Einthoven's triangle.
      The peak-to-peak change in the direction (the change in the DVL) was highly
      correlated with tidal volume. Low-pass filtering of the ECG produced a better
      correlation between tidal volume and the change in the DVL, when the cutoff
      frequency was set at 20-45 Hz. A tidal volume of less than 1.21 was correlated
      more highly with the change in the DVL than a tidal volume of more than 1.21 A
      combination of leads I and III produced the best correlation between tidal volume
      and the change in the DVL, compared with other combinations. The posture of the
      subject had some effects on the slope of the linear regression between tidal
      volume and the change in the DVL.

PMID- 8882905
TI  - Accuracy verification of a PSD-equipped camera-based photostereometric system
      developed for measuring cranial movements in six degrees of freedom.
AB  - The overall objective of this research is to develop a new type of X-ray
      television that allows quantitative analysis of jaw movement. Previous X-ray
      televisions require the patient's head to be held immobile in a normalized
      orientation by means of a positioning jig. This immobilization, however, is
      somewhat time consuming and also restricts natural jaw movements. In order to
      avoid these problems, we have been developing an automatic head-positioning
      system, consisting of two subsystems: a robotized chair and a head-position
      sensor. This paper describes the latter sensing subsystem and focuses on its
      measurement accuracy. To obtain the position and orientation of the head, two
      video cameras, equipped with a position-sensitive device (PSD), detect the three
      dimensional positions of four non-coplanar LED markers mounted on the head. The
      position data obtained is then utilized to operate the robotized chair so as to
      hold the head in the same orientation. Accuracy verification study revealed that
      the overall error of the LED position lay within 1.56 mm (2.8% of total range of
      the motion. 55 mm) and the spatial resolution at all LEDs was 0.19 mm when using
      an averaging filter.

PMID- 8882907
TI  - Waveform estimation techniques for event-related bioelectric signals: a study of
      performance.
AB  - Many bioelectric signals result from the electrical response of a physiological
      system to an impulse that can be internal (ECG signals) or external (evoked
      potentials). A comparative study of performance of seven waveform estimation
      techniques used for event-related signals that are time-locked to a stimulus is
      presented in this paper. Computer generate 1 signals and noise for several signal
      to-noise ratios (SNRs) are used to make ensembles of simulated noisy waveforms.
      The performance of each technique is numerically investigated using the root-mean
      squared error and two well known SNR estimators. The results show that an
      adaptive impulse correlated filter performs the best. It is capable of estimating
      the deterministic component of the signal and removes the noise uncorrelated with
      stimulus even if this noise is colored and without the need for prealignment.

PMID- 8882908
TI  - George Winokur: the man, the clinical scientist, the editor.

PMID- 8882910
TI  - Nonverbal attunement between depressed patients and an interviewer predicts
      subsequent improvement.
AB  - Depressed patients' support-seeking behaviour and the responses to this behaviour
      by others (support-giving) are presumed to play a causal role in depression. In
      interactions between normals, attuning nonverbal behaviour (i.e., equalizing
      levels of specific behavioural activities) is important for satisfaction of the
      participants with the interaction. We investigated the attunement of nonverbal
      support-seeking and support-giving of 31 depressed patients and 1 interviewers
      during a 20-min admission interview. We defined attunement as the absolute
      difference between patients' and interviewers' nonverbal behaviour. It was found
      that the more attunement increased over the interview, the more favourable the
      subsequent course of depression was. The findings emphasize the potential role of
      interpersonal processes in depression.

PMID- 8882909
TI  - Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood
      disorders.
AB  - Disturbances in dopaminergic systems have been implicated in the etiology of mood
      disorders. Although genetic factors also play an important role, no major gene
      has been identified. We conducted an association study using the dopamine D2, D3
      and D4 receptor, and transporter gene polymorphisms, comparing 101 mood-disorder
      patients (52 bipolar and 49 unipolar) and 100 controls. Our results suggest that
      there is a significant association between the dopamine D4 receptor gene and mood
      disorders, especially major depression, but no association between the other
      polymorphisms and mood disorders. Further investigations are needed to clarify
      the clinical significance of this association in the pathophysiology of mood
      disorders.

PMID- 8882911
TI  - Alterations in iron metabolism and the erythron in major depression: further
      evidence for a chronic inflammatory process.
AB  - There is now some evidence that major depression is accompanied by biochemical
      and immune changes pointing to the presence of a chronic inflammatory response.
      The latter condition is reportedly characterized by changes in iron (Fe)
      metabolism and the erythron, such as decreased serum Fe and transferrin (Tf) and
      increased serum ferritin, lower number of red blood cells (RBC), lower hematocrit
      (Htc) and hemoglobin (Hb). The aim of the present study was to examine Fe
      metabolism and the erythron in 38 major depressed subjects versus 15 normal
      volunteers, as well as the effects of antidepressant treatments on these
      variables. Major depressed subjects had significantly lower serum Fe and Tf, a
      lower number of RBC, lower Htc and Hb, and a significantly increased number of
      reticulocytes than normal controls. Serum ferritin was significantly higher in
      major depressed patients with melancholia than in those with simple major
      depression and normal controls. Mean corpuscular volume (MCV), MC Hb (MCH), MC Hb
      concentration (MCHC) and RBC distribution width (RDW) were not significantly
      different between major depressed subjects and normal controls. Treatment with
      antidepressants during 5 weeks had no significant effect on the alterations in
      number of RBC and reticulocytes, Htc, Hb, Fe and Tf. There were significant
      relationships between the above Fe and erythron variables and established immune
      inflammatory markers of major depression, e.g., lowered serum albumin and zinc
      and the increased electrophoretically-separated alpha 1-globulin fraction. The
      results suggest that the disorders in Fe metabolism and the erythron during major
      depression may be induced by the immune-inflammatory response in that illness.

PMID- 8882912
TI  - Blood coagulation and platelet aggregation in major depression.
AB  - Recently, it was found that the plasma of depressed patients significantly
      reduced the primary and secondary platelet aggregation to aggregating agents,
      such as ADP and collagen, in platelet rich plasma (PRP) of normal volunteers.
      Other authors found significantly decreased maximum amplitudes of adrenaline
      induced platelet aggregation in major depressed patients versus normal controls.
      The aim of the present study was to examine platelet aggregation and blood
      coagulation in depression. Toward this end, the authors have measured secondary
      platelet aggregation to ADP and collagen, and the activated partial
      thromboplastin time (APTT) and prothrombin time (PT) in 16 normal volunteers, 16
      minor, 40 simple major and 23 melancholic subjects. There were no significant
      differences in ADP- or collagen-induced platelet aggregability, APTT or PT
      between normal controls, minor, simple major or melancholic depressed patients.
      There were no significant relationships between severity of depression and APTT,
      PT or platelet aggregability to ADP or collagen. It is concluded that blood
      coagulation and platelet aggregability to ADP and collagen are probably not
      disordered in major depression.

PMID- 8882913
TI  - Personality traits in subjects with bipolar I disorder in remission.
AB  - This study compared the personality traits of subjects with bipolar I disorder in
      remission to the personality traits of subjects with no history of any mental
      illness. Subjects were assessed as part of a prospective, multicenter,
      naturalistic study of mood disorders. Diagnoses were rendered according to
      Research Diagnostic Criteria, through use of the Schedule for Affective Disorders
      and Schizophrenia - Lifetime Version. A total of 30 euthymic bipolar I subjects
      were compared to 974 never-ill subjects on 17 personality scales selected for
      their relevance to mood disorders. The subjects with bipolar I disorder in
      remission had more aberrant scores on 6 of the 17 personality measures, including
      Emotional Stability, Objectivity, Neuroticism, Ego Resiliency, Ego Control, and
      Hysterical Factor. These findings indicate that patients with bipolar I disorder
      in remission have personality traits that differ from those of normal controls.

PMID- 8882914
TI  - Sunny hospital rooms expedite recovery from severe and refractory depressions.
AB  - Bright light therapy is an effective treatment for seasonal affective disorder,
      an uncommon condition marked by mild winter depression. Bright lights have been
      used as adjuncts in the pharmacological treatment of other types of depressive
      illness. The rooms in our psychiatric inpatient unit are so placed that half are
      bright and sunny and the rest are not. Reasoning that some patients were getting
      light therapy inadvertently, we compared the lengths of stay of depressed
      patients in sunny rooms with those of patients in dull rooms. Those in sunny
      rooms had an average stay of 16.9 days compared to 19.5 days for those in dull
      rooms, a difference of 2.6 days (15%): P < 0.05.

PMID- 8882915
TI  - The validity of observed depression as a criteria for mood disorders in patients
      with acute stroke.
AB  - The validity of observed depression as a criteria for major or minor depression
      was assessed among 301 patients with acute stroke. Patients who acknowledged a
      depressed mood or loss of interest (standard depression) were compared to
      patients who denied depression but were 'observed' to be depressed (non-standard
      depression) for the clinical correlates of depression. Although standard and non
      standard major depressions had some clinical correlates such as increased
      frequency of female gender and prior psychiatric history, standard major
      depression patients had a significantly higher frequency of left hemisphere
      lesions than the non-standard major depression patients. These results support
      the validity of 'observed' depression as a criteria for major depression but also
      suggest the possibility that failure to report depressed mood may identify a
      condition with a different etiology than depression that is recognized and
      acknowledged. Observed depression, however, was not validated among patients with
      minor depression since there were no clinical or phenomenological differences
      from non-depression.

PMID- 8882916
TI  - Anxiety and autonomic regulation in major depressive disorder: an exploratory
      study.
AB  - Spectral analysis of fluctuations in heart rate and blood pressure was employed
      to explore sympathetic and parasympathetic cardiovascular control mechanisms in
      relation to trait anxiety in major depressive disorder Sixteen drug-free female
      depressed patients were divided into two groups: those who were high on trait
      anxiety (HTA, n = 9) and those who were normal or low on trait anxiety (LTA, n =
      7). In patients and age-matched female controls (n = 10), heart rate (HR), blood
      pressure (BP; Finapres device) and respiration were recorded during a period of
      supine rest (10 min), orthostatic challenge (60 degrees head-up tilting, 8 min),
      and post-orthostatic supine rest (8 min). Power spectra were calculated over the
      last 4 min of these three situations for HR, systolic BP, as well as for
      respiration. Spectral density was assessed for three frequency bands: low (0.02
      0.06 Hz), mid (0.07-0.14 Hz) and high (0.15-0.50 Hz). Patients did not differ
      from controls during supine rest. During orthostatic challenge, HTA patients
      showed significantly more HR increase and suppression of high-frequency
      fluctuations of HR (suggesting stronger vagal inhibition) in comparison with the
      controls; this effect was accompanied by a significant increase in respiratory
      frequency. Both patients groups did not show the normal increase in mid-frequency
      band fluctuations of BP during orthostatic challenge, indicating reduced
      sympathetic activation. Low-frequency fluctuations of HR, as well as respiratory
      frequency during post-orthostatic supine rest of the HTA patients were
      significantly increased versus controls. This exploratory study indicates that
      trait anxiety may be a relevant factor when evaluating parasympathetic and
      sympathetic dysbalances in the state of a major depressive disorder.

PMID- 8882917
TI  - Primary dysthymia: a study of several psychosocial, endocrine and immune
      correlates.
AB  - The relationship between primary dysthymia (chronic, low grade depression) and
      indices of major and minor life stresses, uplifts and coping styles was examined.
      Additionally, circulating lymphocyte subsets were assessed in dysthymic patients
      to determine their relationship to stress/coping factors or plasma levels of
      cortisol, ACTH or norepinephrine. Primary dysthymia was found to be associated
      with increased minor stressors (daily hassles), reduced uplifts, as well as
      particular reliance on emotion-focused rather than problem-oriented coping
      strategies. Interestingly, among dysthymics, the early onset group exhibited a
      greater degree of hassles and greater emotion-focused coping compared to the late
      onset subgroup. Although hassles and coping styles were correlated with depressed
      mood, only coping styles predicted severity of depressed affect. It seems that
      although dysthymia is characterized by increased hassles and reduced uplifts,
      these variables do not distinguish between the severity of the depressive affect,
      whereas the coping styles employed in the face of the increased hassles and
      reduced uplifts are more closely aligned with depression severity. Dysthymia was
      associated with elevated levels of circulating natural killer (NK) cells. Since
      levels of plasma cortisol, ACTH or norepinephrine were not increased in the
      dysthymic subjects, it is likely that the elevated NK cell number was unrelated
      to these neuroendorcrine measures. In control subjects circulating NK cells were
      inversely related to the severity of hassles recently encountered, while in
      dysthymic patients stress and coping factors were unrelated to NK cell numbers.
      Thus, it appears that the altered NK cells in dysthymic patients were not related
      to the increased stress perception and altered coping which characterize these
      patients.

PMID- 8882918
TI  - Developments in the drug treatment of panic disorder: what is the place of the
      selective serotonin reuptake inhibitors?
AB  - Panic disorder is becoming better recognised and understood as a chronic,
      debilitating but treatable condition. Drug treatment options shown by adequate
      research to be beneficial in this condition include mainly the benzodiazepine
      alprazolam, the tricyclic antidepressants (TCAs) imipramine and clomipramine, the
      monoamine oxidase inhibitor (MAOI) phenelzine, and the newer selective serotonin
      reuptake inhibitors (SSRIs) fluvoxamine and paroxetine. Alprazolam, although
      approved for use in panic disorder in the US and very widely used, is associated
      with a risk of dependence and withdrawal syndromes. Given that depression
      frequently occurs as a comorbid condition with panic disorder the use of
      antidepressants is a logical choice. Among the antidepressants, MAOIs are little
      used in panic disorder, mainly because of their potential for precipitating
      hypertensive crises if tyramine is ingested. TCAs are widely used and are
      effective but they are associated with initial activation, or 'jitteriness', have
      a 4-6-week time lag before onset of beneficial effect and produce troublesome
      side effects in a high proportion of patients, particularly during long-term use.
      TCAs are also cardiotoxic in overdosage, and panic disorder patients with
      comorbid depression are at high risk of attempted suicide. Serotonin
      dysregulation has been implicated in the pathogenesis of anxiety disorders in
      general, and panic disorder in particular. Among the TCAs, those with an effect
      on serotonin reuptake are most effective in panic disorder. SSRIs are
      specifically active on serotonin reuptake and do not have anticholinergic effects
      or act on the noradrenergic system. There is a clear pharmacological rationale
      for believing that SSRIs should be as effective as TCAs in panic disorder and
      better tolerated. Accumulating clinical research evidence supports this
      hypothesis. Further comparative studies with standard agents and additional long
      term studies to support the initial long-term data with paroxetine are needed to
      confirm SSRIs as drug treatment of choice in panic disorder.

PMID- 8882919
TI  - Depression in former school-age mothers and community comparison subjects.
AB  - This paper examines the lifetime prevalence and correlates of major depressive
      disorder in a cohort of former school-age mothers and compares the prevalence and
      correlates to those found in women of the same age, ethnicity, and geographical
      location as the school-age mothers. The sociodemographic characteristics show
      some striking differences. The former young mothers were less likely to be on
      public assistance (19% vs 42%), but were more likely to be working (78% vs. 55%),
      to have completed high school or college and to meet the DSM-III criteria for
      depression (10.7% vs. 4.9%) than the sample of community women. The only factor
      related to depression in the former school-age mothers was a diagnosis of
      drug/alcohol abuse or dependence.

PMID- 8882920
TI  - A randomised controlled out-patient trial of cognitive-behavioural treatment for
      children and adolescents with depression: 9-month follow-up.
AB  - Nine-month outcome data of a randomized controlled out-patient trial of cognitive
      behavioural treatment (CBT) for children and adolescents with depression are
      presented. CBT was compared with a non-focussed intervention (NFI) in 56
      subjects. At 9 months after thr termination of the trial, 21 children (37.5%)
      fulfilled criteria for a psychiatric disorder (DSM-III-R), out of whom 15 (26.8%)
      had a depressive illness. However, 25 subjects (45%) reported depressive symptoms
      of significant severity to suggest a depressive episode during the previous 9
      month period. Both treatment groups maintained a significant improvement on all
      psychosocial measures since the post-treatment assessment. No significant
      treatment effect was established. Low self-esteem at the time of referral,
      predicted presence of psychiatric disorder, and child-reported scores of
      depressive symptoms and low self-esteem at follow-up. The research and clinical
      implications for the treatment of depressive disorders in young life are
      discussed.

PMID- 8882921
TI  - Jefferson receives patent for new blood test to improve diagnosis of prostate
      cancer.

PMID- 8882922
TI  - Management of locally advanced prostate cancer.
AB  - The staging and treatment of prostate cancer are complex, particularly in
      patients with clinical disease that has advanced locally beyond the confines of
      the gland. Management choices are made more difficult by a paucity of quality
      randomized and controlled studies. Staging has traditionally relied on digital
      rectal examination, which is now being augmented by improved noninvasive
      radiologic studies. Radiation is the most common form of treatment today, and
      newer techniques are being examined and compared to external-beam therapy.
      Surgical intervention as monotherapy has failed to show a survival advantage.
      Current approaches treatment appear to be evolving toward combination therapies,
      potentially incorporating hormonal manipulation. Patients with locally advanced
      disease should be encouraged to enter prospective clinical trials.

PMID- 8882923
TI  - Month-long postoperative radiotherapy and 5-FU improve survival in rectal cancer.

PMID- 8882924
TI  - Management of hot flushes due to endocrine therapy for prostate carcinoma.
AB  - Endocrine manipulation plays a crucial role in the treatment of advanced prostate
      carcinoma. Recent enthusiasm for earlier use of endocrine therapy has increased
      the significance of diminishing treatment-related side effects, particularly
      vasomotor hot flushes, to ensure long-term patient compliance. Treatments that
      lower serum testosterone, such as orchiectomy or luteinizing hormone-releasing
      hormone (LHRH) analogs, cause hot flushes in over half of men. Lack of regulatory
      feedback in the hypothalamus from circulating serum testosterone is the presumed
      mechanism of hot flushes in these men. Most often, hot flushes are only mildly
      bothersome and can be tolerated without the need for treatment. However, if
      flushes are particularly annoying or problematic, treatment should be offered.
      Small doses of diethylstilbestrol (DES) are effective in relieving hot flushes
      but cause gynecomastia. Megestrol acetate, at a dose of 20 mg bid, completely
      eliminates hot flushes in most men, and the dose can be progressively lowered in
      some.

PMID- 8882925
TI  - Health insurance: coverage of autologous bone marrow transplantation for breast
      cancer.

PMID- 8882926
TI  - Prognostic factors in low-stage nonseminomatous testicular cancer.
AB  - Whether patients with clinical stage I nonseminomatous testicular germ-cell
      cancer (NSGCT) should be treated with orchiectomy and retroperitoneal lymph node
      dissection (RPLND) or orchiectomy and surveillance remains controversial.
      Proponents of the former approach cite the uncertainty and risks of monitoring
      young men who may harbor occult metastases, while proponents of the latter
      strategy contend that surgical staging overtreats 60% to 70% of men. Over the
      last few years, prognostic factors in the primary testicular tumor have helped
      clinicians make more rational decisions about whether RPLND or surveillance
      should follow initial orchiectomy. As of 1996, the most clinically useful
      prognostic factors are the percentage of embryonal carcinoma and the presence or
      absence of vascular invasion by tumor cells in the primary tumor. Ongoing work
      with flow cytometry, image analysis, proliferation markers, and oncogene and
      tumor-suppressor gene markers may allow us to further stratify patients as to
      their likelihood of occult metastases and permit rational "risk-adaptive"
      treatment.

PMID- 8882927
TI  - New donor leukocyte approaches may improve outcomes in relapsed CML post
      transplant.

PMID- 8882929
TI  - Antisense gene therapy trials underway in patients with CML.

PMID- 8882928
TI  - Management of esophageal cancer.
AB  - The standard approaches of surgery or radiotherapy cure only a minority of
      patients with esophageal cancer. Because of these poor results and the frequent
      systemic pattern of recurrences, combined-modality therapy employing chemotherapy
      has been extensively studied. Preoperative chemotherapy, both alone and given
      concurrently with radiation, has not shown a significant impact on survival and
      remains investigational. Concurrent chemoradiation as definitive therapy is an
      alternative to surgery for localized disease. Paclitaxel and vinorelbine have
      significant activity as single agents in metastatic disease. Paclitaxel is
      currently under investigation in combination therapy for metastatic disease, as a
      radiosensitizer for locally advanced disease, and as preoperative therapy. For
      palliation of locally advanced esophageal cancer, a variety of endoscopic
      techniques are available to relieve dysphagia. Laboratory studies have identified
      growth factor pathways and tumor-suppressor genes as potential new pharmacologic
      targets.

PMID- 8882931
TI  - How to better communicate cancer risk to patients.

PMID- 8882930
TI  - Data review shows fruits and vegetables can block major cancers.

PMID- 8882932
TI  - Parameters for plaque formation in the potency assay of Japanese measles
      vaccines.
AB  - Parameters for plaque formation by measles vaccine strains licensed in Japan were
      studied. For the plaque test, inoculum volume was one of the critical factors for
      obtaining an appropriate titre of the sample. A linear relationship between the
      inoculum volume and the apparent reciprocal titre was discovered, enabling the
      comparison of absolute titres. Another factor affecting the infectivity was the
      strain-specific temperature sensitivity in the plaque assay. Although all the
      vaccine strains tested showed the highest titre at 35 degrees C, the pattern of
      the temperature sensitivity differed from one strain to another. These factors
      must be taken into consideration in order to obtain an appropriate titre of a
      vaccine virus.

PMID- 8882933
TI  - Evaluation of electrophoretic immunoblotting for the detection of antibodies
      against the bovine leukosis virus in cattle.
AB  - Six antigen preparations of bovine leukemia virus, including affinity-purified
      glycoprotein gp51, gradient-purified fetal lamb kidney-bovine leukemia virus
      antigen, and four crude antigens, were used in combination with several groups of
      cattle sera, for the evaluation of electrophoretic immunoblotting as a
      serological test method. Sera (89) from cattle naturally-infected with bovine
      leukosis virus, a panel of reference sera from infected and uninfected cattle
      (18), and serial bleedings from experimentally-infected cows (4) were used. Major
      differences between the six antigen preparations were observed in their
      reactivity with the various sera. The immunological variabilities of these
      antigens were confirmed further by their reactions with a gp51-specific
      monoclonal antibody. The known immunodominant gp51 failed as a reliable indicator
      for the serological status of the sera in blots when compared to the results on
      the same sera, two gp51-specific ELISAs and the agar gel immunodiffusion test
      were used as reference tests. There was a lack of staining of gp51 antigen by
      many sera, probably due to the labile nature of the gp51 molecule. On the other
      hand, non-specific staining in the gp51 region appeared with high frequency in
      some antigens. Antibody staining of the internal viral protein p24 correlated
      well with the results of the three reference tests. Other bands stained
      infrequently and were of no diagnostic value.

PMID- 8882934
TI  - Identification of peptides mimicking the antigenicity and immunogenicity of
      conformational epitopes on Japanese encephalitis virus protein using synthetic
      peptide libraries.
AB  - Monoclonal antibodies (mAbs) N.03 and N.08 that recognize conformational epitopes
      on the prM protein of Japanese encephalitis virus (JEV) were analyzed to identify
      their peptide ligands by using a novel approach that combined two different
      synthetic peptide libraries. Immunoscreening of a library containing 20(5)
      sequences of pentapeptides revealed that the ligands for N.03 and N.08 had motif
      sequences, (Y/W/F)GG(I/L/M) and (N/Q)WY(D/E), respectively. To select higher
      affinity ligands, we synthesized and screened another type of library with 20
      peptide mixtures that were based on the identified motif, where only one amino
      acid position was defined; and the process was reiterated for the remaining
      undefined positions. Consequently, the peptides YGGIYMNG and QWYDDR were
      identified as peptide ligands of N.03 and N.08, respectively. These peptides
      bound specifically to the antigen-combining sites of the mAbs as confirmed by
      competitive binding assays. Mouse antisera directed against the peptide YGGIYMNG
      specifically recognized JEV, while those against QWYDDR did not. These data
      demonstrated that peptide ligands which reproduce or mimic the immunogenicity as
      well as the antigenicity of conformational epitopes can be at least partly
      identified using this approach. This approach may be useful for analyzing
      conformational epitopes, which are generally difficult to characterize, and might
      provide a step toward vaccine development when applied to protective mAbs.

PMID- 8882935
TI  - Phosphatidylserine binding to solid-phase rhabdoviral peptides: a new method to
      study phospholipid/viral protein interactions.
AB  - A new method is described for the study of phosphatidylserine binding to
      rhabdoviral peptides by using solid-phase assays. This new assay could probably
      be extended to study the interactions between host membrane phospholipid and
      viral proteins in other viruses. By using labeled and hydrated phosphatidylserine
      (PS), PS-binding to solid-phase 15-mer peptides (pepscan) could map putative
      phospholipid-binding regions of the glycoprotein G of viral haemorrhagic
      septicaemia virus (VHSV), a salmonid rhabdovirus. The major PS-binding region of
      27 aa (aa82-109, p2) did not only bind PS, but also phosphatidylethanolamine (PE)
      and phosphatidylcholine (PC). Extraction of the PS bound to solid-phase p2 by a
      variety of chemical compounds and competition experiments with several
      phospholipid-related compounds showed that PS-Binding to p2 was dependent on not
      only hydrophobic, but also ionic interactions, as suggested by prior work on
      phospholipid interactions in other rhabdoviruses. Saturation/competition
      experiments with labeled and cold PS, PE and PC also showed that the reaction
      probably takes place between high molecular weight aggregates of hydrated
      phospholipids and several molecules of solid-phase p2. This assay has been used
      previously to detect hydrophobic amino acid heptad-repeats in rhabdoviruses and
      when anti-p2 antibodies to VHSV were obtained they were capable of inhibiting
      VHSV-induced cell to cell fusion.

PMID- 8882936
TI  - Expression and purification of the seven nonstructural proteins of the flavivirus
      Kunjin in the E. coli and the baculovirus expression systems.
AB  - All seven nonstructural (ns) proteins of the flavivirus Kunjin (KUN) ranging from
      NS1 to NS5 were expressed either alone or as fusion proteins with Glutathione-S
      transferase (GST). High level expression of recombinant proteins was achieved in
      Spodoptera frugiperda (Sf9) cells using the baculovirus expression system in
      contrast to the low level of expression in E. coli. The order of the level of
      expression of the recombinant fusion proteins per 4 x 10(7) Sf9 cells was: GST
      NS5 (yields approximately 4-5 mg) > GST-delta NS3 (approximately 1-2 mg) > GST-4A
      (approximately 1 mg) > GST-2B (approximately 0.5-1 mg) > GST-2A (approximately
      0.5 mg) > GST-4B (approximately 0.1-0.2 mg). NS1 protein was expressed in a
      native form at the level of approximately 2-4 mg per 4 x 10(7) Sf9 cells. All the
      GST-fusion proteins were purified by adsorption on Glutathione Sepharose (GS)
      beads from solubilized lysates of Sf9 cells infected with the recombinant
      baculoviruses, or of E. coli cultures transformed with the expression plasmid and
      induced with IPTG. Only delta NS3 protein was recovered intact by removing GST
      from the fusion protein by digestion with Factor Xa protease. Attempts to cleave
      off the GST moiety from all the other purified recombinant proteins resulted
      either in inefficient cleavage or in degradation of the proteins. No GST-NS5 but
      from 20 to 50% of the purified GST-NS2A, GST-NS2B, GST-delta NS3, GST-NS4A, and
      GST-NS4B was eluted off the GS beads by adding glutathione. Thus, KUN purified
      recombinant proteins, either in eluted form or while immobilized on GS beads,
      could be used to raise monospecific antibodies, to perform functional assays or
      to participate in protein-protein or RNA-protein binding reactions.

PMID- 8882937
TI  - Use of non-radioactive probes for VP4 typing of human rotaviruses.
AB  - The rotavirus outer capsid proteins VP4 and VP7 determine the P- and G-serotypes,
      respectively, of the virus. Three types of VP4 protein are commonly found in
      human rotaviruses (P4, P6 and P8) which are encoded by distinct VP4 gene alleles.
      We developed a non-radioactive Northern hybridization method for the P-genotyping
      of rotavirus field isolates. Double-stranded RNA was isolated from faecal
      specimens of rotavirus positive patients. Digoxigenin (DIG)-labelled cDNA probes
      derived from the VP4 gene of the standard strains RV5 (P4), ST3 (P6) and RV4 (P8)
      were used to discriminate between the different alleles. Although the P4 probe
      exhibited cross-reactivity with some P8 samples, the P6 and P8 probes were found
      to be type-specific. In addition, the probes did not react with standard strains
      representative of other defined human and animal rotavirus P-types. Use of these
      probes on viral RNA of faecal origin allowed approximately 70% of samples to be
      assigned a P-type. This method complements PCR- and EIA-based P-typing methods,
      is relatively inexpensive and is readily applicable to large numbers of samples,
      thus proving useful for epidemiological studies.

PMID- 8882938
TI  - Polymerase chain reaction amplification of the thymidine kinase and protein
      kinase-related genes of channel catfish virus and a putative pilchard
      herpesvirus.
AB  - Polymerase chain reaction (PCR) amplification assays were developed for the
      detection of thymidine kinase (TK) and protein kinase (PK)-related genes of the
      channel catfish virus (CCV). Two pairs of primers were constructed based on the
      published nucleotide sequences of CCV and were used to amplify the expected
      fragments of 584 and 755 bp for the TK and PK-related genes, respectively. The
      amplified fragments were shown to be specific for each of the target genes by
      chemiluminescence Southern blot hybridisation with a digoxigenin-labelled 20-base
      internal probe. The optimised CCV PCR assay can be used to amplify TK- and PK
      related genes in other mammalian and avian herpesviruses. The CCV TK PCR assay
      also amplified a TK-like gene in some pilchard's gills and tissues obtained in
      the recent epizootic of pilchard kills in New Zealand.

PMID- 8882939
TI  - Comparison of capillary blood versus venous blood samples in the assessment of
      immunity to measles.
AB  - Seroepidemiological investigations are essential for assessing the efficacy of
      measles vaccination programmes. However, when large-scale sampling is needed, a
      major difficulty is the problem of taking venous blood, especially in children.
      An alternative method is the collection of capillary blood samples spotted on
      filter papers. The eluted extract from these 'blood' spots can be used instead of
      serum samples for measles laboratory diagnosis or investigations. Measles
      antibody detection is readily carried out by ELISA on serum samples. The same
      technique can be used on eluates from capillary blood spots. Measles antibody
      titres determined on matched serum and blood spot samples from 27 children were
      compared. A strong correlation was found between the results obtained with the
      two methods of blood sampling.

PMID- 8882940
TI  - A fluorescence-based quantitative PCR method for investigation of pseudorabies
      virus latency.
AB  - A quantitative PCR method was developed in order to quantitate the number of
      copies of Pseudorabies virus (PRV) genome present in tissues from infected pigs.
      The method is based on the use of an internal standard that differs from the
      target DNA by a deletion of ten base pairs, and that is co-amplified with the
      target DNA. The resulting PCR products are labelled with a fluorescent primer and
      are then separated and detected by means of an automated sequencer. The assay was
      found to be specific and sensitive, allowing the detection of five copies of
      viral DNA among 10(6) host cells. The method was used successfully to quantitate
      the number of PRV DNA copies in trigeminal ganglia samples from infected pigs
      during the acute and the latent stages of the infection. Between 12 and 3.10(5)
      copies of viral genome per 10(6) neuronal cells were detected in these tissues
      which is consistent with data published previously.

PMID- 8882941
TI  - Production of non-infectious human immunodeficiency virus-like particles which
      package specifically viral RNA.
AB  - A recombinant vector that rapidly produces large amounts of human
      immunodeficiency virus (HIV) virus-like particles (VLPs) was constructed. This
      vector lacks LTR sequences and a functional nef gene. The VLPs produced are non
      infectious but similar in structure to mature, infectious HIV virions. They
      package specifically HIV RNAs containing appropriate signals and do not package
      abundant cellular mRNAs (e.g. actin). In the system described here, efficient
      particle production and release is decoupled from infection. Use of this VLP
      system offers many advantages over the study of infectious virions, permitting
      the expression of mutant phenotypes which interfere with virus infectivity.

PMID- 8882942
TI  - A polymerase chain reaction for the detection of nucleopolyhedroviruses in
      infected insects: the fate of the Spodoptera littoralis virus in Locusta
      migratoria.
AB  - The Spodoptera littoralis nucleopolyhedrovirus (SlNPV) is a potential pest
      control agent of Spodoptera spp. As part of our studies to establish the use of
      this virus, a polymerase chain reaction (PCR)-based method was developed for the
      detection of viral DNA in infected insects. PCR amplification of the polyhedrin
      sequences enabled the detection of low levels of viral DNA directly from viral
      occlusion bodies or from total larval DNA. The use of different sets of synthetic
      DNA primers allowed us to differentiate between SlNPV and the Autographa
      californica NPV (AcNPV) and to identify a new AcNPV variant isolated from a
      cotton pest, Pectinophora gossypiella NPV. The PCR method was also used to test
      for the possible infection of Locusta migratoria larvae by SlNPV, reported by
      Bensimon et al., 1987. The progress of SlNPV infection in L. migratoria larvae
      was monitored by PCR for 2 weeks. The reaction revealed decreasing amounts of
      viral DNA in infected larvae. During this time, no signs of disease were observed
      in the infected locusts.

PMID- 8882943
TI  - Development and application of HHV-6 antigen capture assay for the detection of
      HHV-6 infections.
AB  - An HHV-6 antigen capture assay measuring gp116/64/54 antigen was developed. This
      ELISA is specific for HHV-6 Variants A and B, does not cross react with other
      human herpesviruses, is sensitive, stable, quantitative, and can detect antigen
      in body fluids and cell cultures. Relative to virus isolation or techniques for
      measuring HHV-6 nucleic acids, the assay is much simpler and less expensive to
      perform. Plasmas/sera (413) obtained from healthy donors, children with Exanthem
      subitum, febrile illnesses, patients with Chronic Fatigue Syndrome, and AIDS
      patients tested by antigen capture assay demonstrated that the assay is useful in
      clinical laboratory settings. The capture assay can also be used to monitor cell
      cultures for virus isolation, production, quantitation, and antiviral agent
      screening.

PMID- 8882944
TI  - A two plasmid co-expression system in Escherichia coli for the production of
      virion-like reverse transcriptase of the human immunodeficiency virus type 1.
AB  - Many bacterial expression systems have been developed to study the reverse
      transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). This enzyme
      exists in the virions as a heterodimer of a 66 kDa (p66) subunit and a 51 kDa
      (p51) subunit, originating through proteolytic maturation of the p66 subunit.
      Most expression systems rely on the processing of p66 by bacterial proteases,
      this results in a p51 subunit with a non-authentic carboxy-terminus. In contrast,
      the expression system described produces an RT with an authentic carboxy
      terminus. This was achieved by the co-expression of the two subunits of HIV-1 RT,
      which were each cloned on a different, compatible plasmid in Escherichia coli,
      and by the use of protease inhibitors during cell lysis. This approach enabled us
      not only to obtain virion-like RT, as verified by mass spectrometry, but also to
      monitor the effect of mutations in one or both subunits on the activity of RT and
      on its sensitivity towards RT inhibitors. The co-expression system described
      represents a useful method to produce HIV-1 RT, both authentic and mutated, in
      quantities that allow large-scale studies on the functional organisation of the
      RT-subunits and the sensitivity of the enzyme to RT inhibitors.

PMID- 8882945
TI  - Sequence-specific, single-primer amplification and detection of PCR products for
      identification of hepatitis viruses.
AB  - A simple system to detect polymerase chain reaction (PCR) amplification products
      was developed. This detection method has the sensitivity and the specificity of
      nested primer PCR amplification or Southern blot hybridization of PCR product.
      Digoxigenin-labeled PCR products were hybridized with a biotinylated probe in
      liquid phase and captured on to microtiter wells coated with antidigoxigenin
      followed by detection with streptavidin-peroxidase. The sensitivity of this assay
      for the detection of hepatitis A virus, hepatitis B virus, and hepatitis C virus
      is equal to that of existing nucleic acid detection systems.

PMID- 8882946
TI  - Highly sensitive qualitative and quantitative detection of reverse transcriptase
      activity: optimization, validation, and comparative analysis with other detection
      systems.
AB  - An ultra-sensitive assay for reverse transcriptase (RT) activity called Amp-RT
      has been developed. An in vitro transcribed heteropolymeric RNA sequence was used
      as a template, and polymerase chain reaction (PCR) amplification with Southern
      blot hybridization served as a detection system for the cDNA product of the
      reaction. Titration of Mg2+ and Mn2+ concentrations using the human
      immunodeficiency virus type 1 (HIV-1) and the human T lymphotropic virus type 1
      (HTLV-I), respectively, showed optimal assay reactivity for both viruses at 2-20
      mM of Mg2+. Analysis of density banded HIV-1 showed that the peak RT activity of
      the assay was associated with the fractions consistent with retrovirus particles.
      The sensitivity of Amp-RT was also compared with that of three conventional RT
      assays by using seven different retroviruses including HIV-1, simian
      immunodeficiency virus (SIV), caprine arthritis-encephalitis virus (CAEV), HTLV-I
      and HTLV-II, simian retrovirus type 2 (SRV-2), and gibbon ape leukemia virus
      (GALV). HTLV-I, HTLV-II, and GALV could not be detected by the three conventional
      RT assays. Amp-RT was able to detect all these viruses in 10(1)-10(3)-fold
      dilutions. Similarly, Amp-RT was found to be 10(3)-10(6)-fold more sensitive than
      the other RT assays in detecting HIV-1, SIV< or CAEV. Culture supernatants from
      uninfected cell lines were all Amp-RT negative. A quantitative Amp-RT assay was
      also developed by using recombinant HIV-1 RT and signal quantitation. The assay
      was found to have a 5 log linear range, and therefore, provides a useful tool for
      quantitating RT and retroviruses. Amp-RT offers a sensitive generic tool for the
      qualitative and quantitative detection of known and unknown retroviruses.

PMID- 8882947
TI  - Detection of human cytomegalovirus polymerase chain reaction products using
      oligonucleotide probes directly conjugated to alkaline phosphatase.
AB  - A 24 base pair oligonucleotide probe directly conjugated to alkaline phosphatase
      has been used to detect immobilised amplicons derived from a cytomegalovirus
      specific polymerase chain reaction (PCR). The sensitivity of detection using a
      highly amplified alkaline phosphatase detection system was four genome
      equivalents and was comparable to the limit of detection using agarose gel
      methods. The mean optical density at 492 nm of samples not known to contain
      cytomegalovirus DNA was 0.085 +/- 0.006 and was well separated from the optical
      density generated from four genome equivalents (absorption at 492 nm: 0.132). The
      assay was used to identify the presence of cytomegalovirus in blood DNA extracts
      from immunocompromised patients in whom conventional ethidium bromide stained
      agarose gel electrophoresis revealed the presence of multiple amplicons. Samples
      yielding an uninterpretable result at both neat and diluted 1 in 20 in the PCR
      gave rise to the highest proportion of positive results (68%) whilst samples that
      produced uninterpretable results neat but were negative at 1 in 20 and vice versa
      gave positive rates of 33.6 and 21.7%, respectively. The use of this assay for
      identifying cytomegalovirus specific PCR products in problematic samples is
      discussed.

PMID- 8882948
TI  - Detection of baculovirus gene expression in insect cells and larvae by low light
      video image analysis.
AB  - Recombinant baculovirus isolates BmNPVluc and AcNPVluc (Kopylova-Sviridova et
      al., 1990) expressing the luc gene in Bombyx mori N-4, and in Sf 9 and
      Trichoplusia ni 368 cells, respectively, were studied. Luc gene expression driven
      by baculovirus regulatory elements was detected by enzyme and photometric assays.
      The expression of recombinant AcNPVluc and BmNPVluc genes in infected larvae of
      the cabbage looper, T. ni and the tomato hornworm Manduca sexta was analyzed by
      low-light video image methods. Expression of the luc gene was detected at high
      levels in both the lepidopteran cells and in third to fifth instar T. ni larvae.
      However, no light emission was detected in M. sexta caterpillars. High levels of
      light emission were detected in T. ni larvae when occlusion bodies containing
      both wild type and recombinant virus were fed to larvae. The results of these
      experiments demonstrate that video image analysis can be used to monitor the
      progression of baculovirus infection in susceptible insect cells and larvae.
      Bioluminescence in recombinant virus infected larvae can be used to determine
      virus host range, to monitor latent virus infection in insect cells and to assess
      the spread of recombinant viruses in the environment. Video image analysis was
      found to be a sensitive method for rapid detection and semiquantitative
      measurement of luc gene expression in baculovirus infected cells and for
      monitoring virus infection in larval tissues.

PMID- 8882949
TI  - Multi-unit anti-BCR-ABL ribozyme therapy in chronic myelogenous leukemia.
AB  - In this review, we summarize and update our data on the development of a multi
      unit anti-BCR/ABL ribozyme. In vitro studies comparing several anti-BCR/ABL
      ribozymes demonstrated that a triple-unit ribozyme is the most efficient.
      Detailed kinetic analysis revealed this ribozyme to have a lower Kcat, most
      likely due to non homologous bases at restriction enzyme sites used in ribozyme
      construction. Delivery of this ribozyme to a BCR/ABL transformed cell line by a
      novel vehicle targeting the folate receptor resulted in a 3 log reduction in
      BCR/ABL mRNA when analyzed by RT-PCR. This delivery strategy reversed the IL-3
      independence of this cell line. Retroviral vectors containing genes coding for
      the multi-unit ribozyme have been constructed and their use to effect BCR/ABL
      transformed cell biology is discussed.

PMID- 8882950
TI  - Circulating clonotypic B cells in the biology of multiple myeloma: speculations
      on the origin of myeloma.
AB  - The population of circulating B cells in myeloma patients includes an apparently
      large but variable subset with the IgH VDJ rearrangement diagnostic for the
      malignant clone of plasma cells in individual myeloma patients. Although the
      biological significance is at present unknown, it is likely that they include
      both malignant and non-malignant clonal relatives of the myeloma plasma cells.
      This article presents speculations on the significance of these cells in the
      origin of myeloma and the relationship between monoclonal gammopathy of
      undetermined significance (MGUS) and frank myeloma. MGUS appears to represent the
      establishment of clonal dominance probably by a chronically antigen-stimulated B
      cell clone. It seems likely that malignant transformation event(s) occurring in a
      clonal daughter cell give rise to myeloma. If correct, this implies that in a
      myeloma patient, non-malignant antigen-responsive B cells expressing the patient
      specific IgH rearrangement coexist in the circulation and probably all lymphoid
      tissues, with their malignant antigen-independent relatives. However, the
      significance one attributes to the clonotypic B cells detected in the blood of
      myeloma patients depends in part on the view one takes of the progression from
      MGUS to myeloma. An alternative perspective is that MGUS represents a dormant
      state of malignancy held in check by controlled apoptosis, arrested cell cycling,
      and/or by immunoregulatory networks. Although lacking in experimental support, if
      this interpretation were correct, myeloma would occur when the regulatory
      mechanisms fail, allowing uncontrolled malignant cell renewal. This alternative
      view would imply that the majority of circulating clonotypic B cells might be
      malignant. Thus, an analysis of the biology of these clonotypic circulating B
      cells, with an emphasis on measures of malignancy, is likely to shed considerable
      light on the events underlying myeloma genesis, progression and spread.

PMID- 8882951
TI  - Concepts of hemopoietic cell amplification. Synergy, redundancy and pleiotropy of
      cytokines affecting the regulation of erythropoiesis.
AB  - Hemopoietic cell amplification in vivo is regulated by various mechanisms which
      appear to be under control of many hemopoietic growth factors. Quiescent stem
      cells can be activated into cell cycle, dividing progenitor cells can reduce
      their cycle time, the differentiation velocity (i.e. transit-time) can be
      manipulated, apoptosis can be prevented, and finally, at least in the murine
      system, migration of cells between the microenvironments in marrow and spleen may
      take place. Perturbations of any of the parameters by which these mechanisms are
      defined, will affect in vivo blood cell production. In this review the
      consequences of these perturbations, and the role of growth factors herein, are
      discussed. These fundamental aspects of the regulation of hemopoiesis are
      illustrated with recent data showing the synergistic, redundant and pleiotropic
      effects of SCF, IL-11, EPO and G-CSF on the in vivo formation of erythrocytes.
      Given the overwhelming number of growth factor-related studies that are now
      appearing, a re-evaluation of data, available in the literature, in the context
      of the mechanistic approach of growth factor-dependent hemopoiesis which is
      presented in this paper, seems to be useful and warranted.

PMID- 8882952
TI  - Aspects concerning busulfan pharmacokinetics and bioavailability.
AB  - Busulfan as a high-dose therapy is an important component of many of the
      myeloablative regimens for both allogeneic and autologous bone marrow
      transplantation (BMT) in adults and children. During the last decade, several
      studies have shown a wide inter- and intra-patient variability of busulfan
      disposition in adults and children. Some of the factors affecting the
      interpatient-variability were identified as circadian rhythmicity, age, disease,
      drug interaction, alteration in hepatic function and recently busulfan
      bioavailability. In adults, pharmacodynamic studies have shown a positive
      correlation between high-systemic exposure of the drug and venocclusive disease
      (VOD). However, pharmacodynamic studies in children did not establish any
      correlation between the systemic exposure and VOD. Drug-monitoring and dose
      adjustment in adults were used successfully to decrease the occurrence of VOD and
      mortality. It was observed that about 20% of the busulfan dose crosses the blood
      brain barrier. The high amount of the drug which enters the brain can probably be
      involved in the CNS toxicities reported. In children, a low rate of toxicity
      combined with a high rate of engraftment failure were observed. Several
      investigators have expressed their concern about the dosage in children and many
      suggested higher doses based on the body surface area for young children.
      However, recently it was shown that busulfan bioavailability varied by 2-fold in
      adults (0.5-1.03) while in children a 6-fold variation was observed (0.22-1.20).
      The access to an intravenous form of busulfan and a deeper understanding of
      pharmacodynamics of the drug might be essential to optimize the treatment, reach
      a successful engraftment and lower the therapy related toxicities.

PMID- 8882953
TI  - Vinorelbine: a new promising drug in Hodgkin's disease.
AB  - Vinorelbine is a new semisynthetic vinca alkaloid that differs chemically from
      vinblastine by a substitution of the catharanthine moiety. The powerful
      cytostatic activity of vinorelbine against murine tumors, human malignant cell
      lines and human tumor xenografts in nude mice has been demonstrated. Phase I-II
      studies of intravenous vinorelbine, administered weekly as single agent or in
      combination chemotherapy have been conducted since 1986. Results suggest that
      vinorelbine has high activity in non-small cell lung cancer, breast cancer and
      cisplatin-resistant ovarian cancer with mild toxicity, being neutropenia the
      major treatment related complication. In this paper we critically review the
      activity of vinorelbine in pretreated Hodgkin's patients. Available results
      strongly suggest the inclusion of this drug in first or second line chemotherapy
      regimens in Hodgkin's disease.

PMID- 8882954
TI  - Clinical and biological significance of serum tumor markers in adult T-cell
      leukemia.
AB  - As the clinical manifestations of adult T-cell leukemia (ATL) can be quite
      diverse, useful indicators for the therapy and prognosis are required for the
      disease. In this review, the clinical and biological significance of serum tumor
      markers at diagnosis in ATL patients is described. Serum lactic dehydrogenase (S
      LDH), serum thymidine kinase (S-TK) and serum parathyroid hormone-related protein
      (S-PTHrP) at diagnosis of ATL showed a correlation with among leukocyte count,
      absolute number of abnormal lymphocytes with polymorphic nuclei, platelet count,
      serum calcium and the length of survival after the initial diagnosis. Serum beta
      2-microglobulin (S-beta 2M) correlated with age, platelet count and survival. A
      statistical correlation existed between these four serum tumor markers. Other
      serum tumor markers such as immunosuppressive acidic protein (S-IAP), ferritin (S
      Ft) and tissue polypeptide antigen (S-TPA) showed no correlation with clinical
      and histological data in ATL patients.

PMID- 8882955
TI  - Role of hydroxyl radicals in radiation-induced activation of lyn tyrosine kinase
      in human B-cell precursors.
AB  - Here we show that exposure of human B-cell precursors to gamma-rays stimulates
      the enzymatic activity of the Src protooncogene family protein tyrosine kinase
      LYN. LYN activation in irradiated cells is not triggered by DNA damage or a
      nuclear signal since gamma-rays effectively stimulated LYN kinase in enucleated B
      cell precursors as well. LYN activation in irradiated cells was abrogated by
      presence of the OH* radical scavenger dimethylsulfoxide and exposure of intact or
      enucleated B-cell precursors to chemically generated OH* radicals instead of
      gamma-rays also triggered LYN kinase activation and enhanced tyrosine
      phosphorylation of multiple electrophoretically distinct protein substrates.
      Thus, OH* radicals appear to be both mandatory and sufficient for radiation
      induced LYN kinase activation in irradiated B-cell precursors. We further present
      evidence which indicates that OH* radicals activate LYN by a novel mechanism
      which involves disruption of inactive LYN-LYN homodimers and monomerization of
      the LYN kinase after proteolytic degradation of a putative LYN-associated adapter
      protein through a cytoplasmic TPCK-sensitive chymotrypsin-like protease following
      its oxidation. LYN kinase plays a pivotal role in initiation of signal cascades
      that affect the proliferation, differentiation, and survival of B-cell
      precursors. Our results prompt the hypothesis that a growth regulatory balance
      might be altered in human B-cell precursors by radiation-induced stimulation of
      LYN kinase.

PMID- 8882956
TI  - Accuracy of immunohistochemistry and flow cytometry in estimating the proportion
      of leukemic cells in S phase in chronic myeloid leukemia patients.
AB  - We compared the proportion of S phase cells in bone marrow and peripheral blood
      samples obtained from 17 patients with chronic myeloid leukemia (CML). Before
      sampling all patients received a one hour i.v. infusion of iododeoxyuridine
      (IdUrd). The proportion of S phase cells was studied by immunohistochemistry
      (IHC) in bone marrow biopsies, and by flow cytometry (FCM) in bone marrow
      aspirates and peripheral blood samples. The IdUrd labelling index (LI) in bone
      marrow biopsy sections (27.5 +/- 1.8%) was significantly higher than the
      proportion of IdUrd labelled cells in bone marrow aspirate (15.1 +/- 2.0%). The
      percentage of S phase cells in peripheral blood was approximately the same as
      that in the aspirate (12.4 +/- 1.3%) and was correlated with that of bone marrow
      aspirate indicating a high degree of the aspirate dilution by peripheral blood.
      It is likely that the differences in % S phase cells in the aspirate and the
      biopsy result from this dilution. Estimates of the % S phase cells in the
      peripheral blood study by IHC and FCM were essentially the same. Samples labelled
      for one hour in vitro resulted in 1.5 fold higher LI than the same samples
      labelled in vivo. We conclude that estimates of the 8% S phase cells in the bone
      marrow of patients with CML should be made by infusing patients with IdUrd or
      BrdUrd with immunohistochemical evaluation of a marrow biopsy. Additionally in
      vitro labelling is not reflective of the percent S phase cells in vivo in
      patients.

PMID- 8882957
TI  - Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors
      of progression-free survival in chronic lymphocytic leukemia and immunocytoma.
AB  - Chronic lymphocytic leukemia (CLL) and immunocytoma (IC) are remarkably
      heterogeneous with regard to their clinical course. The current staging systems
      can distinguish prognostic subgroups, but do not seem to predict the risk of
      disease progression of an individual patient with sufficient accuracy. Given the
      increase of treatment options for CLL and IC, additional parameters are needed to
      decide which patients may benefit from early or intensified treatment. It has
      been shown that two biochemical markers, serum beta 2-microglobulin (s-beta 2M)
      and serum thymidine kinase (s-TK), might identify CLL and IC patients at high
      risk of disease progression. Therefore, the prognostic value of these two serum
      parameters was compared with a panel of several established prognostic factors in
      a prospective clinical trial. 113 patients with CLL and 41 patients with IC (mean
      age +/- SD 63.9 +/- 10.7 years) were included. The following parameters were
      determined: histopathological diagnosis (IC vs. CLL), age, sex, performance
      status (Karnofsky index), B symptoms, peripheral blood lymphocyte count, platelet
      count, blood hemoglobin, serum lactate dehydrogenase (s-LDH), s-beta 2M, s-TK,
      serum creatinine, number of lymph node areas involved, prior therapy, and the
      time from diagnosis to inclusion in the study. Univariate analyses showed that
      nine parameters (Karnofsky index, peripheral blood lymphocytosis, platelet count,
      blood hemoglobin, lymph node areas involved, pretreatment, s-LDH, s-beta 2M, and
      s-TK) significantly predicted progression-free survival. In a Cox regression
      model, only four of these parameters provided independent prognostic information
      on progression-free survival: 1. s-beta 2M, 2. Karnofsky index, 3. platelet
      count, and 4. s-TK. The results show that s-beta 2M and s-TK independently
      predict progression-free survival in patients with CLL and IC, and suggest that
      these prognostic factors may allow an improved prediction of progression-free
      survival, particularly in early disease stages.

PMID- 8882958
TI  - Hematologic recovery and survival of lymphoma patients after autologous stem-cell
      transplantation: comparison of bone marrow and peripheral blood progenitor cells.
AB  - Autologous stem-cell transplantation is widely used as part of the treatment of
      poor prognosis lymphoma patients. Since 1986, peripheral blood progenitor cells
      (PBPC) mobilized by chemotherapy and/or hematopoietic growth factors have
      progressively been used instead of autologous bone marrow (BM) cells. Toxicity,
      engraftment and long-term outcome were compared in a population of relapsing or
      refractory lymphoma patients given high-dose therapy. During 1986 to 1993, 150
      patients with refractory or relapsed non-Hodgkin's lymphomas (n = 93) or
      Hodgkin's disease (n = 57) received intensive therapy followed by the reinjection
      of BM (n = 72) or PBPC (n = 78). PBPC were collected by aphereses during the
      phase of hematologic recovery after mobilization by chemotherapy alone (n = 36)
      or associated with GCSF (n = 43). Conditioning regimens included chemotherapy
      alone in 77%, associated with total body irradiation (TBI) in 23%. After stem
      cell reinfusion, 55% of the PBPC group received GCSF versus 24% in the BM group.
      Results show that the median time to neutrophil counts > 500/microliters and
      platelets > 50,000/microliters was significantly shorter in the PBPC than the BM
      group, respectively 13 versus 23 days and 18 versus 26 days (P < 0.05). This
      difference remained significant (P < 0.05) when patients were stratified
      according to the administration or not of GCSF after transplantation. PBPC
      grafting after high-dose therapy was associated with a median reduction of the
      hospital stay of 10 days. The majority of patients (90%) maintained normal blood
      counts at 3 months, and no secondary graft failure was observed in either group.
      The use of TBI in the conditioning regimen was the only significant factor
      affecting long-term hematologic recovery. For relapsing patients with
      histologically aggressive lymphomas, overall survival and failure-free survival
      were similar in both groups. In conclusion, PBPC transplantation is a safe
      procedure associated with improvement of hematopoietic recovery and a shortened
      hospital stay.

PMID- 8882960
TI  - Analysis of the colonization of unirradiated and irradiated SCID mice by human
      lymphoma and non-malignant lymphoid cells.
AB  - We have evaluated the severe combined immunodeficient (SCID) mouse as an in-vivo
      model for the study of non-Hodgkin's lymphomas (NHL). Characterization of the
      immune system of the animals in our SCID mouse colony was carried out to assess
      the numbers of lymphoid cells present, to determine natural killer (NK) cell
      activity as a function of age and to examine the histology of the lymphoid
      organs. In this study four human NHL established cell lines (Daudi, Namalwa,
      U937, MC116), lymphoma cells from four fresh NHL biopsies and normal peripheral
      blood mononuclear cells (PBMC) and bone marrow cells were investigated, after
      intraperitoneal injection into the mice. The presence of the human NHL cells in
      the peritoneum and spleen was assessed by FACS analysis. The colonization
      potential was investigated in a range of tissues by polymerase chain reaction
      (PCR) amplification of human repetitive sequences. These studies revealed clear
      differences in the abilities of the NHL cell types to colonize the SCID mice.
      Namalwa, Daudi and U937 cells demonstrated the highest efficiency of colonization
      and readily formed tumours, whereas MC116, the NHL biopsy cell populations and
      the non-malignant lymphoid cells showed little ability to survive and colonize
      other tissues in the SCID mice. Whole body irradiation of the SCID mice appeared
      to improve the survival of human PBMC, NHL biopsy cells and MC116 cells in the
      peritoneum, but had little effect on their colonization potential. The
      significance of these studies is discussed.

PMID- 8882959
TI  - Plasma M-CSF as an indicator of response to chemotherapy in adult T cell leukemia
      patients.
AB  - The plasma concentration of macrophage colony-stimulating factor (M-CSF) was
      measured in 10 patients with acute type adult T cell leukemia (ATL) during the
      clinical course before and after chemotherapy. M-CSF concentration decreased
      significantly when the patients achieved complete remission (CR) or partial
      remission (PR) (t-test: p = 0.0001). Five of the patients showed disease
      progression after several months of PR, and plasma M-CSF increased at that time
      (t-test: p = 0.0456). Thus, plasma M-CSF concentration appeared to accurately
      reflect the disease activity in ATL. In support of these results, all three ATL
      cell lines established from these patients secreted M-CSF in vitro after
      stimulation with phorbol myristate acetate (PMA) or concanavalin A (Con A).
      Plasma M-CSF concentration, however, increased transiently when the patients were
      febrile (t-test: p = 0.0001), even though their ATL condition was unchanged.
      Taken together, these results indicate that there are two sources of increased
      plasma M-CSF concentration in ATL; ATL cells themselves and normal parenchymal
      cells that cause this increase as the result of elevated body temperature due to
      inflammation.

PMID- 8882961
TI  - Expression of tenascin is related to histologic malignancy and angiogenesis in b
      cell non-Hodgkin's lymphomas.
AB  - The topography of and the area covered by tenascin, laminin and type IV collagen
      (all components of the subendothelial basement membrane), and the microvessel
      area (an index of angiogenesis), as evaluated with factor VIII, were investigated
      immunohistochemically in 61 B-cell non-Hodgkin's lymphomas (B-NHL) and 30 benign
      lymphadenopathies as controls. The three components were located in the
      microvessels and in a microvessel-bound stromal reticular network, the expression
      of tenascin being always more extended and finer than the other components. Of
      the lymphadenopathies, reactive and atypical lymphoid hyperplasias showed vessels
      and stromal network in the interfollicular zone only, whereas in Castleman's and
      angioimmunoblastic forms these structures were widely scattered in the tissue,
      and the area of the three components and that of the microvessels were
      significantly larger. Of the low-grade B-NHL, follicular subtypes had vessels and
      stromal network confined to the interfollicular inflammatory zone, but not in
      tumor follicles, whereas these structures were irregularly distributed throughout
      the small lymphocytic subtype. The levels of areas in low-grade B-NHL overlapped
      those of Castleman's and angioimmunoblastic lymphadenopathies. Among the
      intermediate-grade tumors, the follicular subtype resembled the follicular
      tumors, and the diffuse subtypes displayed vessels and stromal network throughout
      the tissue in close association with the neoplastic cells, and with significant
      increments of both the tenascin and the microvessel areas, but with a significant
      reduction of both the laminin and the type IV collagen areas. Distribution was
      similar in high-grade B-NHL, but tenascin and microvessel area variations, on the
      one hand, and those of laminin and type IV collagen areas were still more
      apparent than in the intermediate-grade. A high correlation was demonstrated in
      all groups of tissues between tenascin and microvessel area. In addition, in the
      diffuse intermediate-grade and high-grade B-NHL highly immature vessels were
      frequently detected by ultramicroscopy. The results show that tenascin expression
      and angiogenesis are closely related, and that both increase in function of tumor
      malignancy. Unlike laminin and type IV collagen, tenascin is associated with
      highly immature vessels in B-NHL. We suggest that tenascin expression and
      angiogenesis are governed by the B-NHL-associated inflammatory infiltrate, as
      well as by the B-NHL cells, particularly in more malignant tumors.

PMID- 8882962
TI  - The treatment of elderly patients with aggressive non-Hodgkin's lymphomas:
      feasibility and efficacy of an intensive multidrug regimen.
AB  - The results of a prospective trial of an 8 week treatment for elderly patients
      with advanced intermediate-high grade NHL are reported. Our aim was to reduce
      general toxicity without losing an antilymphoma effect. For this reason the use
      of growth factor was studied. We also analysed the behavior of different
      histological groups (E + F vs G + H). From November 1991 to November 1993 100
      patients older than 65 years with combination intermediate-high grade advanced
      stage NHL were treated with the P-VEBEC regimen, an original including epirubicin
      50 mg/sqm, cyclophosphamide 300 mg/sqm and etoposide 100 mg/sqm on weeks 1, 3, 5,
      7; vinblastine 5 mg/sqm and bleomycin 5 mg/sqm on weeks 2, 4, 6, 8; prednisone 50
      mg/sqm/day per os in the first two weeks and thereafter every other day .46 pts
      received rG-CSF 5 micrograms/Kg/day throughout the treatment starting on day 2 of
      every week for 4 consecutive days. Twenty eight pts had B symptoms, 41 had bulky
      disease, 37 LDH levels above normal, 50 stage IV patients and 30 had bone marrow
      involvement. Sixty two percent achieved a complete remission (CR). Adverse
      prognostic factors for CR were E and F histology, stage IV disease, bone marrow
      infiltration, serum LDH levels above normal, international Prognostic Index
      (I.I.) intermediate-high and high risk categories and relative dose intensity
      (RDI) less than 0.80. Severe toxicity was rarely recorded and only one toxic
      death was observed. With a median follow-up of 33 months OS, DFS and EFS were
      44%, 60% and 30% respectively. EFS was influenced by stage, BM involvement, level
      of LDH and I.I. intermediate-high and high risks. The 52 patients with DLCL
      (diffuse large cell lymphomas--G + H according to WF) did better with a higher
      CR, OS, DFS and EFS rates, than the other WF subtypes. In conclusion P-VEBEC is a
      feasible combination to use in elderly patients, mainly in DLCL. The use of rG
      CSF improves the RDI. A RDI > 0.80 could play a role in improving the outcome,
      especially in patients with adverse prognostic factors. For other subgroups
      another schedule is probably justified.

PMID- 8882963
TI  - Clinical and hematological characteristics of hepatosplenic T gamma/delta
      lymphoma with isochromosome for long arm of chromosome 7.
AB  - Hepatosplenic T gamma/delta lymphoma is a rare entity of peripheral T cell
      lymphoma. Three of 386 patients with non-Hodgkin's lymphoma in our institute were
      found to have this subtype of lymphoma. All had chromosomal abnormalities of
      isochromosome 7q and trisomy 8. The clinical and hematological features of these
      three patients are reported. All were males with ages ranging from 23 to 29
      years. Initial presentation comprised purpura and variable degree of
      hepatosplenomegaly. None had superficial lymphadenopathy. Hematologically, they
      showed pictures resembling immune related thrombocytopenia and/or hemolytic
      anemia. Examination of the bone marrows revealed hypercellularity with increased
      number of megakaryocytes and erythroid cells and various degrees of abnormal
      lymphoid cell infiltration. The histopathologic section of the spleen from one
      patient who underwent splenectomy revealed abnormal cell infiltration in the
      sinusoids of the red pulp. Lymphoma cells showed T gamma/delta lymphoid
      immunophenotype (CD3+ CD2+ CD4- CD8-, TCR delta-1+, and beta F1-). The platelet
      counts were elevated transiently after initial treatment with corticosteroids,
      but the condition soon deteriorated. All died of refractory lymphoma five to nine
      months after diagnosis. Review of the literature, showed that only four other
      cases have been reported until now and although no cytogenetic data were
      available for these patients, they had very similar clinical pictures as those in
      this series. It is suggested that hepatosplenic T gamma/delta lymphoma represents
      a rare, but distinct, clinicopathological and cytogenetic entity.

PMID- 8882964
TI  - Treatment of three patients with systemic mastocytosis with interferon alpha-2b.
AB  - It has been reported that the administration of interferon alpha-2b is of
      potential benefit in the treatment of mastocytosis based on a single patient
      study (NEJM, Feb 27, 1992, 326(9):619-623). Following this report, we
      administered interferon alpha-2b at a dose of 4 to 5 million units per square
      meter of body surface area for at least 12 months to one patient with
      mastocytosis with an associated hematologic disorder (patient 1), one patient
      with aggressive systemic mastocytosis (patient 2), and one patient with indolent
      mastocytosis (patient 3). Patients were monitored with the following clinical and
      laboratory parameters: serial bone marrow biopsies and aspirates, patient log of
      histamine release attacks, medication dependency, plasma tryptase levels, serum
      lactate dehydrogenase (LDH) levels, white blood cell counts and differentials,
      extent of urticaria pigmentosa lesions, bony involvement, and extent of
      gastrointestinal involvement and hepatomegaly. We also examined the ability of
      interferon alpha-2b to inhibit recombinant human stem cell factor (rhSCF)
      dependent mast cell proliferation from CD34+ bone marrow-derived cells. All
      patients demonstrated continued progression of disease in one or more clinical
      criteria at one year of therapy. Similarly, interferon alpha-2b did not inhibit
      the culture of mast cells from CD34+ bone marrow-derived cells in the presence of
      SCF. Thus, in our study of three patients with systemic mastocytosis, treatment
      with interferon alpha-2b was found to be ineffective in controlling progression
      of disease.

PMID- 8882965
TI  - Intermittent 2-hour intravenous infusions of 2-chlorodeoxyadenosine in the
      treatment of 110 patients with refractory or previously untreated B-cell chronic
      lymphocytic leukemia.
AB  - The purpose of our study was to determine the effectiveness of 2-CdA in 2-hour
      intravenous infusions in the treatment of B-CLL. One hundred and ten patients
      with B-CLL received 1 to 10 courses of 2-CdA (median 2.5) at a dosage of 0.12
      mg/kg daily for 5 consecutive days. Eighteen of them were untreated and 92
      relapsed or became refractory to previous therapeutic modalities. Complete
      remission (CR) was achieved in 8 (7.3%) and partial remission (PR) in 35 patients
      (31.8%) giving an overall response rate of 39.1%. In 3 patients, cross-resistance
      to fludarabine was noticed. Toxic effects of 2-CdA were more frequently observed
      in previously treated patients. Hemorrhagic complications due to drug-induced
      thrombocytopenia were noticed in 25 (22.7%) and severe infections including
      sepsis in 14 (12.7%) patients.

PMID- 8882966
TI  - Serum G-CSF levels in primary myelofibrosis and chronic neutrophilic leukemia as
      estimated by the highly sensitive chemiluminescence enzyme immunoassay (CLEIA).
AB  - We previously reported that serum granulocyte colony stimulating factor levels of
      chronic myelogenous leukemia patients in chronic phase (CP) are significantly
      lower than those of healthy persons or other hematological malignancies as
      assessed by chemiluminescence enzyme immunoassay (CLEIA). In this study, we
      clarify the difference in serum G-CSF levels between patients with primary
      myelofibrosis (PMF, myelofibrosis with myeloid metaplasia; MMM) and those with
      secondary myelofibrosis caused by several hematological disorders, using the same
      highly sensitive CLEIA method. It is clearly demonstrated that serum G-CSF levels
      of the patients with PMF and chronic neutrophilic leukemia (CNL) are extremely
      low, similar to those in patients with CML in CP in this study. From these data,
      it is speculated that the abnormal proliferation of granulocytes in PMF and CNL
      may not be due to the stimulation by G-CSF, and that a negative feedback
      mechanism might exist between peripheral granulocytes and serum G-CSF.

PMID- 8882967
TI  - Clinical relevance of the breakpoint sites within the M-BCR in 50 patients from
      Argentina with chronic myeloid leukemia.
AB  - Fifty patients from Argentina with chronic myeloid leukemia (CML) were studied in
      order to characterize the breakpoint site within the major breakpoint cluster
      region (M-BCR) and its relationship with the duration of the chronic phase (CP).
      The DNA digestion with the restriction enzymes: Bgl II, BAM HI and Hind III and
      hybridization with the 1.2Kb Hind III-Bgl II bcr probe showed that 56% of cases
      had the breakpoint in 5'M-bcr region and the remaining 44% in 3'M-bcr region. The
      duration of chronic phase from diagnosis to the onset of the blast crisis (BC)
      was correlated with the location of the breakpoint within the M-bcr and no
      statistical differences were observed between the 5' and the 3' groups. These
      data indicate that the breakpoint site within the bcr gene is not a prognostic
      indicator of the duration of CP of the disease.

PMID- 8882968
TI  - Adult T-cell leukemia (ATL) with an unusual immunophenotype and a high cellular
      proliferation rate.
AB  - A patient with adult T-cell leukemia (ATL) characterized by a suppressor
      phenotype is reported. A 52-year-old mulatto male presented with symptoms and
      signs of hypercalcemia. His laboratory finding disclosed a peripheral blood
      specimen with abnormal cells characterized by a rather pleomorphic morphology and
      polylobated nucleous typical of ATL cells. Serum calcium and LDH were 18.2 mg/dl
      and 1373 IU, respectively. The phenotype of these cells was CD2+, CD4-, CD8+,
      CD28+ associated with the expression of activated antigens such as CD25, CD38,
      CD71 and CD30. Ki-67 positive were found in 20% of cells. The argyrophilic stain
      for nuclear organizer regions (AgNORs) was shown one cluster in 35% of abnormal
      cells. The serum antibodies were positive against human T-cell lymphotropic virus
      type I (HTLV-I) and clinical features were compatible with the diagnosis of ATL
      acute type. The combination therapy with cyclophosphamide, vincristine,
      prednisone decreased the number of leukemic cells but the clinical course was
      aggressive. He only responded transiently to treatment and died of multiorgan
      failure due to uncontrollable septicemia two weeks after admission.

PMID- 8882969
TI  - Cutaneous monoblastic leukemia as a first sign of relapse six years after
      autologous bone marrow transplantation for acute leukemia.
AB  - A patient with acute monoblastic leukemia (AML, M5A) was treated successfully in
      December 1987. In 1993 after 6 years in complete remission, she presented with an
      intracutaneous nodular mass on her right upper arm which was resected in toto and
      shown to be undifferentiated monoblastic leukemia. Two further chloroma lesions
      were excised in July 1994 and March 1995 respectively. Bone marrow cytology and
      histology always showed a continuing complete remission with no evidence of
      leukemia relapse. In July 1995 she presented with a disseminated skin infiltrate
      and a relapse with 80% monoblasts in the bone marrow. After one course of
      chemotherapy (Idarubicin/Ara-C), a second complete remission was achieved and her
      leukemic skin infiltrate disappeared completely. This case illustrates that
      chloromas of the skin can occur as late as 6 years after treatment for AML and
      also emphasizes that the occurrence of a chloroma does not necessarily mean
      immediate leukemia relapse. It also stresses that a second complete remission can
      be achieved with standard AML-induction therapy despite widespread leukemic skin
      infiltrates in such patients.

PMID- 8882971
TI  - Quantitative analysis of triglycerides using atmospheric pressure chemical
      ionization-mass spectrometry.
AB  - Atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) was used for
      quantitative analysis of triglycerides (TG) separated by reverse-phase high
      performance liquid chromatography. APCI-MS was used for analysis of mono-acid TG
      standards containing deuterated internal standard, of a synthetic mixture of
      heterogeneous TG, of randomized and normal soybean oils and of randomized and
      normal lard samples. Quantitation of the TG by four approaches based on APCI-MS
      were compared, and these were compared to quantitation obtained using liquid
      chromatography (LC) with flame-ionization detection (FID). The APCI-MS methods
      were based on (i) calibration curves from data for mono-acid TG standards, (ii)
      response factors obtained from a synthetic mixture of TG, (iii) response factors
      calculated from comparison of randomized samples to their statistically expected
      compositions, and (iv) response factors calculated from comparison of fatty acid
      (FA) compositions calculated from TG compositions to FA compositions obtained by
      calibrated gas chromatography (GC) with FID. Response factors derived from a
      synthetic mixture were not widely applicable to samples of disparate composition.
      The TG compositions obtained using APCI-MS data without application of response
      factors had average relative errors very similar to those obtained using LC-FID.
      Numerous TG species were identified using LC/APCI-MS which were undetected using
      LC-FID. Two quantitation methods, based on response factors calculated from
      randomized samples or on response factors calculated from FA compositions, both
      gave similar results for all samples. The TG compositions obtained using response
      factors calculated from FA compositions showed less average relative error than
      was obtained from LC-FID data, and were in good agreement with predicted
      compositions for the synthetic mixture and for randomized soybean oil and lard
      samples.

PMID- 8882972
TI  - Postparturition changes in the triacylglycerols of cow colostrum.
AB  - The changes in the triacylglycerol (TAG) composition of colostrum fat of three
      cows were studied. In addition to the determination of fatty acid composition by
      gas chromatography, the distribution of TAG according to the acyl carbon number
      (ACN) and molecular weight was analyzed utilizing both supercritical fluid
      chromatography (SFC) and ammonia negative-ion chemical ionization mass
      spectrometry (MS). Colostrum TG contained substantially less stearic and oleic
      acids and more myristic and palmitic acids than the normal Finnish milk fat. The
      major trends in the changes of fatty acids and TAG were similar for each cow,
      although clear differences between individuals were found. During the first week
      of parturition, the proportions of short-chain fatty acids (C4-C10) typically
      increased as well as those of stearic and oleic acids, whereas the relative
      amounts of C12-C16 acids decreased, especially those of myristic and palmitic
      acids. Distinct changes occurred also in TAG distributions: the proportions of
      molecules with ACN 38-40 increased and those with ACN 44-48 decreased. Although
      there were distinct differences between individuals shortly after delivery, both
      the fatty acid compositions and TAG distributions of the milk samples of the cows
      started to resemble each other after one week. The theoretical profiles of
      colostrum TAG calculated based on the fatty acid compositions differed clearly
      from the ACN distributions analyzed by SFC and MS. Thus, the analysis of TAG is
      essential, because the changes in molecular species composition of colostrum TAG
      cannot be estimated according to the fatty acid analysis alone.

PMID- 8882973
TI  - Effect of castration and hormonal supplementation on cholesterol cholelithiasis
      in the male hamster.
AB  - This study examined the effect of castration and dietary hormonal supplementation
      on cholesterol cholelithiasis in male hamsters. Animals fed a standard lithogenic
      diet developed cholesterol gallstones (17%) after 6 wk, while castrated hamsters
      did not form any stones. Addition of a synthetic androgen, methyltestosterone, to
      the lithogenic diet induced cholelithiasis in castrated animals (50%). The biles
      of normal and castrated-hormone supplemented hamsters had cholesterol saturation
      indices of 1.0 and 1.1, respectively, while the bile of the castrated animals
      remained unsaturated (0.6). The ratio of cholic acid/chenodeoxycholic acid in
      bile increased after castration, but returned to normal levels following hormonal
      supplementation. Biliary cholesterol carriers were separated by
      ultracentrifugation. Animals in the stone-forming groups (normal and castrated
      hormone treated) had a significant proportion of their biliary cholesterol in
      vesicles (44 and 46%, respectively); castrated hamsters had less cholesterol in
      vesicle form (9%). The molar ratio of cholesterol/phospholipid in vesicles was
      reduced after castration (0.93 vs. 0.42) and increased by hormonal
      supplementation (1.89). In conclusion, when compared to normal male hamsters fed
      a standard lithogenic diet, castration reduced the cholesterol saturation of
      bile, lowered the vesicular/micellar ratio in bile, and inhibited cholesterol
      cholelithiasis. Dietary androgen supplementation increased the lithogenicity of
      bile, resulting in stone formation in castrated animals.

PMID- 8882974
TI  - Dietary fat alters biliary lipid secretion in the hamster.
AB  - Dietary fat has been found to alter the incidence of cholesterol gallstones in
      hamsters: butterfat intensifies while safflower oil reduces lithiasis. WE not
      report how dietary fat affects bile flow and biliary lipid secretion in this
      model. Male hamsters were fed one of three experimental diets: a control diet
      (containing 0.3% cholesterol); control diet + 4.0% butterfat; or control diet +
      4.0% safflower oil. After three weeks, bile samples were collected via an
      external biliary fistula. The endogenous bile acid pool was depleted for 120 min
      followed by increasing rates of taurocholate infusion for 160 min. Basal
      secretion of biliary lipids was measured during the bile acid depletion period.
      Basal bile flow and bile acid output were not significantly different in the
      three groups. Dietary butterfat increased basal cholesterol output compared to
      the control diet (0.037 vs. 0.025 mumol/min.kg, respectively); safflower oil did
      not change cholesterol output (0.027 mumol/min.kg). Hamsters fed butterfat or
      safflower oil secreted more phospholipid (0.171 and 0.178 mumol/min.kg,
      respectively) than controls (0.131 mumol/min.kg). The cholesterol/phospholipid
      output ratio of the butterfat group was higher than the safflower oil group
      (0.220 vs. 0.153, respectively). Effects of dietary fat on several relationships
      between file flow and biliary lipid secretion were analyzed by linear regression
      using the data for the entire bile collection period (bile acid depletion and
      taurocholate infusion). Butterfat and safflower oil did not change either bile
      acid dependent or bile acid independent bile flow. Hamsters fed butterfat had a
      higher linkage coefficient (slope) of cholesterol vs. bile acid output than the
      safflower oil group (0.023 vs. 0.009, respectively). The linkage coefficient of
      phospholipid vs. bile acid output of the butterfat group was higher than the
      controls (0.278 vs. 0.185, respectively). In summary, butterfat induced a high
      cholesterol and phospholipid secretion with a high cholesterol/phospholipid
      output ratio; safflower oil induced a high phospholipid secretion with a low
      cholesterol/phospholipid output ratio. Butterfat and safflower oil have different
      effects on biliary lipid secretion. These differences in biliary lipid secretion
      may explain, in part, how butterfat and safflower oil differ in affecting
      gallstone formation in hamsters.

PMID- 8882970
TI  - Acyl-CoA binding proteins: multiplicity and function.
AB  - The physiological role of long-chain fatty acyl-CoA is thought to be primarily in
      intermediary metabolism of fatty acids. However, recent data show that nM to
      microM levels of these lipophilic molecules are potent regulators of cell
      functions in vitro. Although long-chain fatty acyl-CoA are present at several
      hundred microM concentration in the cell, very little long-chain fatty acyl-CoA
      actually exists as free or unbound molecules, but rather is bound with high
      affinity to membrane lipids and/or proteins. Recently, there is growing awareness
      that cytosol contains nonenzymatic proteins also capable of binding long-chain
      fatty acyl-CoA with high affinity. Although the identity of the cytosolic long
      chain fatty acyl-CoA binding protein(s) has been the subject of some controversy,
      there is growing evidence that several diverse nonenzymatic cytosolic proteins
      will bind long-chain fatty acyl-CoA. Not only does acyl-CoA binding protein
      specifically bind medium and long-chain fatty acyl-CoA (LCFA-CoA), but ubiquitous
      proteins with multiple ligand specificities such as the fatty acid binding
      proteins and sterol carrier protein-2 also bind LCFA-CoA with high affinity. The
      potential of these acyl-CoA binding proteins to influence the level of free LCFA
      CoA and thereby the amount of LCFA-CoA bound to regulatory sites in proteins and
      enzymes is only now being examined in detail. The purpose of this article is to
      explore the identity, nature, function, and pathobiology of these fascinating
      newly discovered long-chain fatty acyl-CoA binding proteins. The relative
      contributions of these three different protein families to LCFA-CoA utilization
      and/or regulation of cellular activities are the focus of new directions in this
      field.

PMID- 8882975
TI  - Effects of dietary heated fats on rat liver enzyme activity.
AB  - The objective of this study was to evaluate the effects of dietary heated fats
      from a commercial deep-fat frying operation on rat liver enzyme activity. The
      fats, partially hydrogenated soybean oil (PHSBO) used for four days and for 7
      days (7-DH) for frying foodstuffs in a commercial restaurant, were fed to rats in
      either free access to food or by pair-feeding graded doses. All diets were
      isocaloric and contained 15 g/100 g of diet. Experiments were conducted with
      control rats fed non-heated (NH) PHSBO diet. Animals fed 7-DH diet in each set of
      experiments had larger amounts of cytochromes P450 and b5 and greater activity of
      NADPH-cytochrome P450 reductase when compared to controls. The activities of
      carnitine palmitoyltransferase-I and isocitrate dehydrogenase were significantly
      lower in rats fed test diets in comparison to controls. A significantly depressed
      activity of glucose 6-phosphate dehydrogenase was also noticed for these animals
      when compared to those fed NH. In addition, liver and microsomal protein
      concentrations were significantly greater in rats fed the used oils in comparison
      to controls, and liver glycogen was significantly lower.

PMID- 8882976
TI  - Effect of dietary vitamin E levels on fatty acid profiles and nonenzymatic lipid
      peroxidation in the guinea pig liver.
AB  - Guinea pigs were fed for five weeks with three diets containing different levels
      of vitamin E: LOW (but nondeficient, 15 mg of vitamin E/kg diet), MEDIUM (150
      mg/kg diet), and HIGH (1,500 mg/kg diet). Dietary vitamin E supplementation did
      not change oxidative stress indicators in the hydrophilic compartment but
      increased liver alpha-tocopherol in a dose-dependent way and strongly decreased
      sensitivity to nonenzymatic in vitro liver lipid peroxidation. This last effect
      was already observed in group MEDIUM, and no further decrease in in vitro lipid
      peroxidation occurred from group MEDIUM to group HIGH. The protective effect of
      vitamin E against in vitro lipid peroxidation was observed even though an optimum
      dietary concentration of vitamin C for this animal model was present in the three
      different vitamin E diets. Both HIGH and LOW vitamin E decreased percentage fatty
      acid unsaturation in all phospholipid fractions from membrane origin in relation
      to group MEDIUM. The results, together with previous information, show that both
      vitamin E and vitamin C at intermediate concentrations are needed for optimal
      protection against lipid peroxidation and loss of fatty acid unsaturation even in
      normal nonstressful conditions. These protective concentrations are higher than
      those needed to avoid deficiency syndromes.

PMID- 8882977
TI  - Fatty acid composition of Danish margarines and shortenings, with special
      emphasis on trans fatty acids.
AB  - Trans fatty acids from hydrogenated vegetable and marine oils could be as
      hypercholesterolemic and atherogenic as saturated fatty acids. Hence, it is
      important to know the fatty acid composition in major food contributors, e.g.,
      margarines and shortenings. In 1992 margarines were examined, and in 1995 brands
      covering the entire Danish market were examined. Significant amounts of trans
      18:1 were found only in hard margarines (mean: 4.2 +/- 2.8%) and shortenings
      (mean: 6.8 +/- 3.1%), whereas the semisoft and soft margarines contained
      substantially less trans-18:1 in 1995 than in 1992. Where marine oils had been
      used to a larger degree the mean trans-monoenoic content was about 15%, of which
      close to 50% was made up of long-chain (C20 and C22) trans fatty acids. A
      noteworthy decrease in the content of trans-18:1 had occurred for the semisoft
      margarines, from 9.8 +/- 6.1% in 1992 to 1.2 +/- 2.2% in 1995. Calculated from
      sales figures, the supply of trans-18:1 plus saturated fatty acids from
      margarines has decreased over this three-year period by 1.4 g/day, which has been
      replaced by cis monounsaturated and polyunsaturated fatty acids.

PMID- 8882978
TI  - Polyunsaturated fatty acids exert antiarrhythmic actions as free acids rather
      than in phospholipids.
AB  - Previous studies have shown that exogenous free n-3 polyunsaturated fatty acids
      (PUFA) can prevent tachyarrhythmias caused by specific agents in isolated cardiac
      myocytes. However, the question as to whether incorporation of the n-3 PUFA into
      membrane phospholipids has the same immediate protective effects remained to be
      answered. To answer this question, we increased the content of n-3 PUFA in the
      phospholipids of cultured neonatal rat myocytes by growing them 2-3 d in a
      culture to which eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in 15
      microM concentration was added. Analysis of the fatty acid composition of
      membrane phospholipids revealed a significantly higher level of EPA and DHA (from
      0.2 to 7.6% and from 1.2 to 6.5%) in cells supplemented with EPA or DHA,
      respectively. The responses of the myocytes grown in normal media or in media
      enriched with the PUFA to arrhythmogenic agents were examined after free fatty
      acids were removed from the medium and the cells. The arrhythmogenic agents used
      were the beta-adrenergic agonist isoproterenol or an elevated extracellular
      concentration of calcium. The results showed that there was no significant
      difference in the induction of tachyarrhythmias by isoproterenol or by elevated
      [Ca2+]o in cells grown in media enriched with PUFA, as compared with cells grown
      in normal media in the absence of the free PUFA. Under the conditions of this
      study, only the unesterified PUFA were able to protect the cardiomyocytes against
      induced arrhythmias. There was no antiarrhythmic effect due to an increased
      fraction of EPA or DHA in membrane phospholipids.

PMID- 8882980
TI  - Sterol composition of phaeodactylum tricornutum as influenced by growth
      temperature and light spectral quality.
AB  - In a detailed sterol analysis of the marine diatom Phaeodactylum tricornutum,
      free sterols as well as esterified and glycosylated conjugates were found. When
      the alga was grown under standard conditions (i.e., at 13 degrees C under white
      light), 64% of total sterols were steryl glycosides. In all sterol classes,
      except steryl esters, (24S)-24-methylcholesta-5,22E-dien-3 beta-ol
      (epibrassicasterol) was the major (80 to 99%) sterol component. Eight other
      sterols were identified. Growth under different light spectral quality (red,
      blue, yellow, and green) at 13 and 23 degrees C was examined. At 23 degrees C, a
      dramatic decrease in total sterol content was observed, especially under blue
      light. The distribution of sterols between free and conjugated forms as well as
      sterol profile inside each class was found to be strongly dependent on the light
      spectral quality at both temperatures.

PMID- 8882979
TI  - Enhancement by ganglioside GT1b of annexin I phosphorylation in bovine mammary
      gland in the presence of phosphatidylserine and Ca2+.
AB  - Ganglioside GT1b and, to a lesser extent, GD3, enhanced phosphorylation of a 36
      kDa protein (the substrate of protein kinase C) in the particulate fraction from
      bovine mammary gland. Sialic acids, asialogangliosides, and GM3 were without
      effect, and GD1a conversely inhibited phosphorylation of the 36 kDa protein. The
      enhanced phosphorylation by GT1b required the simultaneous presence of
      phosphatidylserine (PS) and Ca2+. The 36 kDa protein reacted with anti-annexin I
      in Western blot analysis. Addition of purified annexin I to the reaction mixture
      containing the particulate fraction increased the extent of phosphorylated 36 kDa
      protein, and the phosphorylation was further enhanced by GT1b. The enhanced
      phosphorylation of annexin I by GT1b was also dependent on PS and Ca2+. When
      annexin I was phosphorylated by purified protein kinase C, GT1b inhibited the
      annexin I phosphorylation. Addition of epidermal growth factor or insulin to the
      particulate fraction had little effect on the enhancement. These results suggest
      that an enzyme or enzymes other than protein kinase C, epidermal growth factor
      receptor kinase, or insulin receptor kinase is responsible for the GT1b- and GD3
      enhanced phosphorylation of annexin I in the presence of PS and Ca2+.

PMID- 8882981
TI  - A simple method for the synthesis of ceramides and radiolabeled analogues.
AB  - A simple method has been developed for the coupling of amines to carboxylic
      acids. N-Fatty-acyl-sphingosine, cerebroside, and GM3, as well as their
      respective [14C] analogues, were synthesized using diethylphosphoryl cyanide as a
      potent coupling agent in the presence of triethylamine. The reaction procedure is
      rapid, racemization-free, and utilizes acids without derivatization. The desired
      ceramide products were obtained in 85-90% yield within one hour. The facile
      method presented here can also be used to synthesize [3H]-N-acyl-labeled, as well
      as [14C] [3H] double-labeled, ceramides.

PMID- 8882983
TI  - Brain relapses in chemotherapy-treated small cell lung cancer: a retrospective
      review of two time-dose regimens of therapeutic brain irradiation.
AB  - The incidence of brain metastases secondary to small cell lung cancer (SCLC) is
      about 35% and the treatment strategy of brain irradiation with respect to dose
      and fractionation is controversial. In order to evaluate treatment outcome of
      brain irradiation in SCLC patients with brain relapse, we retrospectively
      evaluated all patients treated with brain irradiation in the eastern part of
      Denmark from 1988 to 1992 (PCI patients excluded). During this 5-year period, 101
      evaluable patients were included (44 females, 57 males) (median age 61 years;
      range, 39-75 years). Forty-four patients, of whom 43 were in extracerebral
      complete remission (CR), received extended course (EC) brain irradiation (> 45
      Gy, treatment schedule > 4 weeks). Fifty-seven patients received short course
      (SC) brain irradiation (< 30 Gy, treatment schedule < 1 week). Among the SC
      treated patients, 14 were in CR, 20 had partial remission or stable disease and
      23 had progressive extracerebral disease. The median survival (from diagnosis of
      brain metastases) in the group receiving irradiation with EC (44 patients) was
      160 days (range, 74-2021 days), while the 57 patients treated with SC had a
      median survival of 88 days (range, 20-948 days) (P = 0.00001, Log-Rank analysis).
      In a subgroup of 14 patients in extracerebral CR, receiving SC irradiation, the
      median survival was 83 days (range, 15-948 days). When the latter patients were
      compared to the 43 patients in CR in the group treated with EC, a statistically
      significant difference was shown (P = 0.034, Log-Rank analysis). Using Cox-hazard
      regression analysis with backward elimination, liver metastases and poor
      performance status were adverse prognostic signs, although the only significant
      parameters of survival were gender (female vs. male, relative risk of dying 1 and
      1.52, P = 0.05) and schedule of brain irradiation (extended course vs. short
      course, relative risk of dying, 0.36 and 1, P < 0.001). Extended course
      irradiation of brain relapse secondary to SCLC seems in general to be of limited
      value, although a significant prolonged survival at approximately 7 weeks, was
      obtained. The prolongation of survival does not seem worthwhile considering the
      length of treatment time (5-6 weeks) compared to SC treatment (1 week). However,
      the data do not permit evaluation of the quality of life of the patients. This
      retrospective evaluation suggests the need for randomized trials with carefully
      planned quality-of-life assessments.

PMID- 8882982
TI  - Intracellular diacylglycerol: a mitogenic second messenger proposable as marker
      of transformation in squamous cell carcinoma of the lung.
AB  - In this study, we examined 50 patients with documented lung cancer projecting in
      the bronchial lumen unilaterally. Bronchial lavage from the affected and
      unaffected sides provided neoplastic and normal cells in which we studied an
      intracellular mitogenic second messenger, diacylglycerol, associated with
      transformation. The levels of diacylglycerol in cells from the affected side were
      compared with that from the healthy side, thus providing an internal control for
      each patient. Our data show that the levels of diacylglycerol in lavage fluid
      relative to affected bronchus are elevated in 56% of all the patients examined.
      This elevation reaches 77% in patients with squamous cell carcinoma, a value of
      sensitivity higher than 'traditional' markers for cancer of the lung. Thus, these
      findings may have significant implications for the use of diacylglycerol
      measurement as a novel biomarker for early detection of lung cancer, and for
      monitoring recurrences after treatment.

PMID- 8882984
TI  - Histopathological grading of response to induction chemotherapy in non-small cell
      lung cancer: a preliminary study.
AB  - Management of locally advanced NSCLC is controversial. Induction chemotherapy
      followed by surgery has become an accepted approach for Stage III disease.
      However, the clinical assessment of the efficacy of preoperative treatment is
      inaccurate. We propose a four-grade histopathological evaluation of the response
      to chemotherapy based on the analysis of 20 evaluable cases and compared with
      clinical outcome. Follow-up ranged from 12 to 68 months. Correlation between
      different grading of necrosis and survival is statistically significant. Based on
      these preliminary results, we suggest that grading of response is a valid
      parameter to evaluate standard regimens and novel drug associations in larger
      trials.

PMID- 8882985
TI  - Is thrombomodulin useful as a tumor marker of a lung cancer?
AB  - To evaluate whether thrombomodulin (TM) can be considered a tumor marker of lung
      cancer, we examined serum TM levels in 179 lung cancer patients by an enzyme
      immunoassay. Further, in 91 resected cases, we also investigated the TM presence
      in lung cancer tissue by an immunohistochemical method. Our findings revealed
      that 58 (32%) of 179 lung cancer patients had higher serum TM levels than our
      cutoff levels. No difference was seen in the serum TM-positive ratio between
      histologic types, but patients with Stage IV disseminated cancer showed a higher
      serum TM-positive ratio than those with Stage I-IIIB localized cancer, especially
      cases of adenocarcinoma. Immunostaining results showed a TM presence in the
      cancer cells of 32 (35%) of 91 lung cancer cases. The TM presence in cancer cells
      was higher in cases with squamous cell carcinoma than with adenocarcinoma; no
      differences were seen among the disease stages. No correlation was found between
      the serum TM and the presence of TM in cancer cells. Further, serum TM status
      appears to have little clinical significance as a method to detect early lung
      cancer or for predicting the recurrence after the surgical excision of a lung
      cancer. Thus, we have concluded that, although serum TM levels are elevated in
      some lung cancer patients, it is doubtful that the TM status is useful as a tumor
      marker of lung cancer.

PMID- 8882987
TI  - Two dose levels of ifosfamide in malignant mesothelioma.
AB  - Thirty-one consecutive patients with histologically proven and symptomatic
      malignant mesothelioma were treated with two dose levels of ifosfamide. The first
      group of 15 patients were given 2.3 g/m2/day for 5 days (group A) and the
      following 16 patients were treated with 1.2 g/m2/day for 5 days of ifosfamide
      (group B). Treatment cycles were repeated every 3 weeks. While the partial
      response rate (PR) in group A was 38.5%, it was only 6.25% in group B (P > 0.05).
      The 95% confidence interval for the difference in PR rates was 3.3-61.2% > The
      overall survival (OAS) of groups A and B were similar (8 months and 9 months,
      respectively). Higher Grade 3-4 myelotoxicity was observed in group A when
      compared to group B (30.8% vs. 18.7%; P > 0.05). In conclusion, a favourable
      response rate could be achieved in malignant mesothelioma with high dose
      ifosfamide at the cost of increased toxicity.

PMID- 8882986
TI  - Interferon alpha-2a and combined chemotherapy as first line treatment in SCLC
      patients: a randomized trial.
AB  - BACKGROUND: Interferons (IFNs) are known to act synergistically with
      antineoplastic agents when applied to SCLC cell cultures. This study was
      conducted in order to detect the clinical benefits, if any, of the addition of
      IFN-alpha in the induction chemotherapy (CT) of SCLC patients. PATIENTS AND
      METHODS: Ninety previously untreated patients with SCLC were randomly assigned to
      receive either CT alone (arm A) or CT plus IFN alpha-2a in a dose of 3 MU/m2
      twice weekly (arm B). CT for both arms consisted of carboplatin 420 mg/m2,
      etoposide 200 mg/m2 and ifosfamide 3.5 g/m2 or epirubicin 80 mg/m2 every 28 days
      for a total of eight cycles. Responding patients received primary site and
      prophylactic cranial irradiation and then had maintenance CT with
      cyclophosphamide 100 mg/m2/day for 20 days every month. Patients in arm B
      received IFN throughout these treatments. RESULTS: Eighty-one patients were
      evaluable for response, 39 in arm A and 42 in arm B. Both arms were comparable in
      terms of age, performance status and extent of disease. Overall response rates
      were not significantly different between the two arms (90% vs. 86%), although
      complete response rate was higher in arm B (38% vs. 28%). More importantly,
      Kaplan-Meier analysis disclosed a clear survival benefit in the arm receiving IFN
      alpha (P < 0.05). For limited disease the difference was even more significant (P
      < 0.0067), while for extensive disease no significant difference was found (P <
      0.35). Fever, fatigue and anorexia were more frequent in arm B (P < 0.001), as
      also leukopenia (P < 0.01). CONCLUSION: The addition of IFN-alpha to induction CT
      appears to confer a survival benefit to SCLC patients but optimal dosing schedule
      has yet to be defined.

PMID- 8882988
TI  - A phase I/II trial of etoposide and cisplatin in extensive small cell lung
      cancer: a cancer and leukemia group B study.
AB  - Patients with untreated extensive small cell lung cancer (SCLC) with CALGB
      performance scores 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and
      cisplatin doses of 20, 30, or 35 mg/m2/day days 1-3 in a Phase I/II format. Of
      the nine patients treated at the 35 mg/m2/day cisplatin dose in the Phase I
      portion of the study, Grade 4 leukopenia occurred in five patients and Grade 4
      thrombocytopenia in four. There were two deaths due to myelosuppression and
      sepsis. This dose was thus considered the maximum tolerated dose (MTD), and a
      Phase II trial was then conducted using this treatment program. In the Phase II
      trial of 39 patients, the objective response rate was 67% (95% confidence
      interval, 50-81%) with 21% complete responses (CI 9-36%). Median survival was
      10.5 months. Grade 4-5 leukopenia was seen in 57% and Grade 4-5 thrombocytopenia
      in 56%. The MTD defined by this Phase I trial represents a 67-100% increase in
      etoposide and a 32-42% increase in cisplatin dosage compared to prior studies.
      The observed objective response rates with this regimen are comparable to studies
      using conventional doses, but hematological toxicity was higher.

PMID- 8882989
TI  - Phase I/II study of combination chemotherapy with cisplatin, carboplatin and
      etoposide in small cell lung cancer.
AB  - A Phase I/II study of combination chemotherapy with cisplatin (CDDP), carboplatin
      (CBDCA) and etoposide (VP-16) (CPVP) was conducted in patients with small cell
      lung cancer. The dose level of etoposide was fixed at 100 mg/m2, while the doses
      of CDDP and CBDCA administered at each of the four steps were 50/200, 60/200,
      60/250 and 70/250 mg/m2, respectively. Nine patients were allocated to each step
      dose group. Adverse effects were evaluated during the first two courses to
      establish the maximum tolerated dose (MTD). As a result, the step 3 doses turned
      out to be the MTD. The dose-limiting factor was hematotoxicity. Gastrointestinal
      toxicity was also present, but was tolerated. The overall response rate in
      patients with measurable or evaluable lesions was 91%. In 22 chemotherapy-naive
      patients, the median survival time was 16.6 months. These results suggest that
      the recommended dose is step 2, and that the CPVP regimen might be both more
      tolerable and more effective than the standard PVP regimen. Based on the above
      findings, CPVP therapy warrants further study in Phase II and III trials.

PMID- 8882990
TI  - Pulmonary blastoma: a rare lung malignancy.
AB  - We describe a case of pulmonary blastoma, a rare lung malignancy which affects a
      younger population. Despite its usually indolent presentation, it is an
      aggressive malignancy with a prognosis similar to that for bronchogenic
      carcinoma.

PMID- 8882991
TI  - Adenocarcinoma of the lung presenting as a diffuse interstitial process in a 25
      year-old man.
AB  - Adenocarcinoma of the lung is rare in young adults, particularly in persons below
      the age of 30. Younger patients tend to present with advanced stages of
      carcinoma, and often have a rapidly deteriorating course. We describe a 25-year
      old male who presented with diffuse interstitial lung disease which was found at
      autopsy to be lymphangitic carcinomatosis of probable pulmonary origin.

PMID- 8882992
TI  - Lung squamous cell carcinoma presenting with brain metastases in an HIV-positive
      patient.
AB  - The case history of a patient with squamous cell carcinoma of the lung and HIV
      infection is described, who presented clinically with CNS symptomatology. No
      association of the tumor with human papilloma virus was found.

PMID- 8882993
TI  - Influence of different exercise protocols on functional capacity and symptoms in
      patients with chronic heart failure.
AB  - This study compares hemodynamic, metabolic, and gas exchange responses,
      catecholamine levels, and symptoms in 35 male patients with chronic heart failure
      (CHF) ([mean +/- SD] age 53 +/- 11 yr; ejection fraction 24 +/- 11%) during three
      differently graded exercise test protocols. On three consecutive days patients
      performed cycle ergometry supine, with prolonged steps (prol BE) and right heart
      catheterization, ramplike cycle ergometry sitting (ramp BE), and ramplike
      treadmill walking (TMW). As in routine clinical practice, the prol BE was
      terminated when pathologic central hemodynamics and/or increased symptomology
      occurred, and ramp BE and TMW due to increased symptomology and/or physician's
      decision. During prol BE at ventilatory threshold (VT) the VO2 (8.6 +/- 1.8 ml.kg
      1.min-1) was lower than during ramp BE (9.3 +/- 2.1 ml.kg-1.min-1) (P < 0.017)
      and TMW (11.8 +/- 2.3 ml.kg-1.min-1) (P < 0.0001). Prol BE, ramp BE, and TMW also
      differed significantly with respect to ventilation (22 +/- 7 l.min-1; 26 +/- 6
      l/min-1; 29 +/- 7 l.min-1; P < 0.01) and heart rate (100 +/- 15 beats.min-1; 103
      +/- 18 beats.min-1; 110 +/- 16 beats.min-1; P < 0.017). No differences were found
      in lactate levels, catecholamine levels, and ratings of leg fatigue and dyspnea.
      At test termination, the peak VO2 during prol BE (100.8 +/- 3.3 ml.kg-1.min-1)
      was lower than during ramp BE (13.3 +/- 4.1 ml.kg-1.min-1) (P < 0.0001) and TMW
      (14.7 +/- 3.4 ml.kg-1.min-1) (P < 0.0001). Peak norepinephrine value during ramp
      BE (4.531 +/- 2.788 nmol.l-1) was higher than during prol BE (3.707 +/- 2.262
      nmol.l-1) (P < 0.001). Among the three tests, no significant differences were
      found for peak values of heart rate, lactate, and ratings of dyspnea. Although
      the VO2.kg-1 at VT was significantly higher during ramp BE and TMW compared to
      prol BE (P < 0.001), the values expressed as a percent of peak VO2.kg-1 were
      significantly lower (70 +/- 4%; 72 +/- 6%; 79 +/- 3%; P < 0.017). A systematic
      effect on aerobic capacity with reduced peak values during ramp BE and TMW was
      demonstrated when test termination was based primarily on pathological findings
      of central hemodynamics from prol BE.

PMID- 8882994
TI  - Optimization of force in the Wingate Test for children with a neuromuscular
      disease.
AB  - Determination of the optimal braking force (Fopt in the Wingate Anaerobic Test
      (WAnT) among healthy people has been determined based on total body mass. The
      abnormal muscle mass to total body mass ratio in individuals with neuromuscular
      disabilities invalidates this approach. This study was intended to validate the
      optimal force obtained from the Force Velocity Test (FVT) and from an estimate of
      lean arm volume as two alternative predictors for the Fopt. Twenty-eight 6- to 16
      yr-old girls and boys with neuromuscular diseases performed the arm WAnT six
      times (three trials in each of two visits) against various braking forces to
      directly determine Fopt. They also performed the arm Force Velocity Test to
      assess optimal force (FoptFVT). Lean arm volume was determined by anthropometry
      (ALV) and water displacement (WLV). Correlations between Fopt on the one hand,
      and FoptFVT, WLV, and ALV on the other, were: R2 = 0.91, 0.81, and 0.82,
      respectively. Total body mass was the worst predictor (R2 = 0.65). Thus, Fopt
      obtained from either FVT or lean arm volume estimate is a useful predictor of the
      Fopt for mean power of the WAnT in children and adolescents with a neuromuscular
      disability.

PMID- 8882995
TI  - Marathon medical services: strategies to reduce runner morbidity.
AB  - Grandma's Marathon has been run each year in June since 1977 in Duluth, MN. It is
      ranked in the top 20 marathons and in 1993 was ranked the ninth largest and
      fourth fastest in the United States. As Grandma's Marathon continues to grow each
      year, so do concerns for the runners' safety. A half marathon was added in 1991
      and earlier race times have been implemented to make the race safer for the
      runners. During the years of 1989-1995, data from the medical tent, weather
      bureau, and race booklets were analyzed using odds ratios to predict factors
      associated with a need for medical assistance. The odds of needing assistance
      were almost two times higher before implementing the half marathon and the odds
      of needing assistance decreased with earlier start times. Except for 1994 when
      the race was later, the percent of finishers seeking medical attention has
      decreased each year, a fact that we feel is a direct result of these race
      changes. Thus, the addition a half marathon and earlier start times can help
      decrease the number of people needing medical assistance.

PMID- 8882996
TI  - Influence of walking volume on health benefits in women post-menopause.
AB  - The health benefits of physical activity are believed to be related more to
      exercise volume than to intensity. In this 24-wk study, we examined the effect of
      walking volume on aerobic fitness, serum lipids, and body composition in women
      post-menopause, a population at risk for coronary artery disease. Of 79 women
      randomly assigned to groups at the outset, 56 completed the study (mean age 61.3
      +/- 5.8). Participants walked at an intensity of 60% peak oxygen uptake (VO2peak)
      for 60 min, 3 d.wk-1 (N = 19) or 5 d.wk-1 (N = 17), or remained sedentary (N =
      20). Walking 3 or 5 d.wk-1 increased VO2peak (ml.kg-1.min-1) by 12% and 14%,
      respectively (P < 0.01). There were no changes in serum lipids in response to
      either program. Percent body fat decreased by 1.1% and 1.3% in those walking 3
      and 5 d.wk-1, respectively; both changes significantly different from the control
      group (P < 0.05). Walking 5 d.wk-1 did not result in more health benefits than 3
      d.wk-1, possibly due to a greater compensatory decline in activities other than
      the walking program, or greater discrepancies between actual and reported
      activity and food intake. Longer-duration programs, or simultaneous changes in
      diet, may be necessary to alter serum lipids in nonobese, normo-lipidemic women
      post-menopause.

PMID- 8882997
TI  - Contractility of the ventilatory pump muscles.
AB  - The ventilatory muscles are striated skeletal muscles, and their in situ function
      is governed by the same relationships that determine the contractile force of
      muscles in vitro. The ventilatory muscles, however, are functionally distinct
      from limb skeletal muscles in several aspects, the most notable being that the
      ventilatory muscles are the only skeletal muscles upon which life depends. Among
      the muscles that participate in ventilation, the diaphragm is closest to its
      optimal resting length at functional residual capacity (FRC) and has the greatest
      capacity for shortening and volume displacement, making it the primary muscle of
      inspiration. All inspiratory muscles shorten when the lung is inflated above FRC,
      but interactions among the various inspiratory muscles make for a wider range of
      high force output than could be achieved by any one muscle group acting in
      isolation. The velocity of inspiratory muscle shortening, especially
      diaphragmatic shortening, causes maximal dynamic inspiratory pressures to be
      substantially lower than maximal static pressures. This effect is especially
      pronounced during maximal voluntary ventilation, maximal exercise, and maximal
      inspiratory flow, volume maneuvers over the full vital capacity. During quiet
      breathing, the ventilatory muscles operate well below the limits of their neural
      activation and contractile performance. During intense activity, however, the
      diaphragmatic excursion approaches its limits over the entire vital capacity, and
      respiratory pressures may near their dynamic maximum. Because the system may
      operate near its available capacities during increased ventilatory demands,
      multiple strategies are available to compensate for deficits. For example, if the
      diaphragm is acutely shortened, it can still generate the required respiratory
      pressure if it receives more neural drive. Alternatively, other muscles can be
      recruited to take over for an impaired diaphragm. Thus, the whole system is
      highly versatile.

PMID- 8882998
TI  - Adaptive strategies of respiratory muscles in response to endurance exercise.
AB  - The purpose of this review is to discuss the adaptive strategies of mammalian
      respiratory muscles in response to whole-body endurance exercise training. It is
      now clear that endurance training results in small (i.e., 20-30%) but significant
      increases in mitochondrial enzyme activity and the activities of key antioxidant
      enzymes (i.e., superoxide dismutase and glutathione peroxidase) within the rodent
      diaphragm. Interestingly, the magnitude of this training-induced increase in
      costal diaphragmatic oxidative and antioxidant enzyme activity is relatively
      independent of the exercise duration and intensity. Although the crural diaphragm
      of rodents is also capable of increasing its oxidative and antioxidant capacity
      in response to endurance training, high-to moderate-intensity exercise of long
      duration is required to promote these changes. Endurance training also increases
      the oxidative capacity of other key rodent inspiratory muscles, such as the
      parasternal intercostals and external intercostals. Furthermore, endurance
      training results in small (approximately 10%) increased in the oxidative capacity
      of key abdominal (expiratory) muscles. Whether the improvement in oxidative
      capacity of respiratory muscles is of significant magnitude to result in
      improvement in respiratory muscle performance remains an unanswered question.

PMID- 8882999
TI  - Respiratory muscle perfusion and energetics during exercise.
AB  - The oxygen cost of breathing and blood flow requirements of the respiratory
      muscles during exercise are discussed along with the implications for limitation
      of locomotor muscle and exercise performance. Findings show that the oxygen cost
      of the hyperpnea achieved during very heavy exercise may approach 15% or more of
      VO2max under conditions that require extraordinary levels of ventilatory work.
      These conditions include those in the highly trained endurance athlete (at VE >
      150 l.min-1), the older athlete at VE of 110-120 l.min-1), and athletic cursorial
      mammals at VO2max--all of whom experience significant expiratory flow limitation
      and sometimes even complete ventilatory limitation during heavy or maximum
      exercise. Rates of blood flow to the respiratory muscles under these peak
      exercise conditions may equal or exceed those to the limb locomotor muscles. The
      hypothesis is advanced that excessive requirements of ventilatory work (and
      therefore VO2 and blood flow) during heavy exercise may cause reflex
      vasoconstriction of locomotor muscles resulting in curtailment of endurance
      exercise performance.

PMID- 8883000
TI  - Respiratory muscle fatigue during exercise: implications for performance.
AB  - Heavy whole-body exercise, requiring a 10- to 15-fold increase in minute
      ventilation, encroaches on the capacities of the respiratory muscle system to
      respond. Recently, using the technique of bilateral phrenic nerve stimulation, it
      has been shown that heavy endurance exercise (> 85% of VO2max) lasting > 8-10 min
      causes diaphragmatic fatigue (15-30% reduction in transdiaphragmatic pressures
      when electrically stimulated at low frequencies [1-20 Hz] supramaximally). The
      fatigue appears to be due to an interaction of diaphragmatic work (i.e., pressure
      production) combined with effects related to exercise intensity (i.e., increased
      blood flow competition with the locomotor muscles and increased production of
      metabolic by-products) and requires > 60 min for recovery. Fitness (i.e., as
      implied from VO2max) appears to allow greater diaphragmatic work for a similar
      degree of fatigue. Unloading the respiratory muscles (with helium/oxygen gas or
      using a pressure-assist device) during heavy exercise < 90-95% of VO2max does not
      appear to alter exercise time, VO2max, or minute ventilation, implying that
      respiratory muscle fatigue plays little role in altering human performance at
      these work intensities. However, unloading the respiratory system with helium at
      work intensities > 90-95% of VO2max has been shown to improve exercise time. This
      would imply that respiratory muscle fatigue may play a role in limiting human
      performance at the extremes of human performance or that other factors related to
      the respiratory system (i.e., alterations in the sensation of dyspnea or
      mechanical load) may play an important role.

PMID- 8883001
TI  - Effects of exercise intensity on 24-h energy expenditure and substrate oxidation.
AB  - The purpose of this study was to determine: 1) the reliability of 24-h
      respiratory calorimetry measurements, and 2) the effects of low- versus high
      intensity exercise on energy expenditure (EE) and substrate oxidation over a 24-h
      period. Eight women (age 28 +/- 4.3 yr) were measured for body composition,
      maximal oxygen consumption while cycling, and EE in three, 24-h calorimeter
      tests, with identical work output but differing intensity during a 60-min
      exercise session. Low-intensity (LI) exercise involved continuous cycling at 50%
      VO2max; whereas high-intensity (HI) exercise involved interval cycling (2 min
      exercise/recovery) at 100% VO2max. Subjects were randomly assigned to the first
      two tests at LI or HI, with the third test at the alternate intensity. No
      differences in EE or respiratory quotient (RQ) during rest, sleep, exercise, or
      over the 24 h were found between the first two tests (C.V. = 6.0%), demonstrating
      the reliability of the measurements. The HI protocol elicited significantly
      higher EE than LI during rest, exercise, and over 24 h, whereas sleeping EE
      approached significance. No significant differences in RQ during rest, sleep, or
      over 24 h were found, but 24-h lipid and carbohydrate oxidation were similar in
      the two protocols. The HI exercise RQ was significantly higher than LI. These
      findings demonstrated higher 24-h EE in the HI than LI protocol, but similar 24-h
      substrate oxidation rates.

PMID- 8883002
TI  - Forearm blood flow by Doppler ultrasound during test and exercise: tests of day
      to-day repeatability.
AB  - The between-day repeatability of simultaneous measures of brachial artery
      diameter (D) (echo Doppler) and mean blood velocity (MBV) (pulsed Doppler) was
      tested during rest and exercise. On 3 separate days, six volunteers performed one
      trial of 1-min rest followed by a step increase in dynamic handgrip exercise for
      4 min which required the lifting and lowering of a 4.4-kg weight (approximately 8
      12% MVC) in a 1s/2s (work/rest) cadence. Measures for MBV and D were collected
      continuously on a beat-by-beat basis during the transition from rest to end
      exercise. The mean rest values over one min, and single data points at 30, 60,
      120, and 240 s of exercise were extracted from the time series data. At all
      exercise time points, MBV was greater than rest (P < 0.05), but these levels were
      not different across test days. Arterial D at all exercise time points ranged
      from 3.8 +/- 0.1 mm to 4.1 +/- 0.1 mm (mean +/- SEM) and did not differ from rest
      (3.9 +/- 0.1 mm) (P > 0.05), nor did D differ between days. The mean between-day
      coefficient of variation for D was 4.08 +/- 0.7% at rest and ranged from 2.90 +/-
      0.4% to 3.96 +/- 0.5% during exercise. The coefficient of variation for MBV was
      13.2 +/- 2.6% at rest and reached 20.2 +/- 3.1% during the final min of exercise;
      the exercise variability was reduced to 14.9 +/- 2.4% by averaging MBV over 3 s
      (the duration of a contraction/relaxation duty cycle) (P < 0.05) with no further
      advantage of averaging over ten 60-s sample periods. The data indicate that, for
      the six subjects tested, Doppler ultrasound measures of arterial MBV and diameter
      during both rest and exercise were reproducible across different test days and
      can be used as a reliable, noninvasive means of testing hypotheses pertaining to
      blood flow control.

PMID- 8883003
TI  - A 20-yr longitudinal study of Olympic oarsmen.
AB  - Nine 1972 silver-medalist oarsmen were studied before the Olympic Games and 10
      and 20 yr later. Peak power, metabolic responses, and heart rate were recorded
      during rowing ergometry; blood lactate was measured following exercise. The
      skinfold equation yielded percent body fat. The average change (multiple analysis
      of variance) among measurements from 1972 to 1992 was 37.5 +/- 3% (P < 0.01).
      Average changes between 1972 and 1982 and between 1982 and 1992 were similar, 17
      and 18%, respectively (P < 0.01). The most significant change between 1972 and
      1992 was decreased peak blood lactate (106%). Decreases in peak power, VE, and
      VO2 (ml.kg-1.min-1) were all similar, approximately 40%, and were significant.
      Body fat increased (from 12.3 to 15.6%), and absolute VO2 and relative VO2 (lean
      body mass) decreased 30% (P < 0.01). Only body weight, heart rate, and O2 pulse
      showed smaller changes, but these changes were still significant (P < 0.05).
      Relative peak VO2 decreased from 65.5 to 46.8 ml.kg-1.min-1 from 1972 to 1992 and
      at a rate of 10%.decade-1. The most significant changes between 1972 and 1982
      were increases in percent body fat (from 12.3 to 16.3%) and decreases in VO2
      values (P < 0.01). There was less change in body fat between 1982 and 1992, but
      lactate significantly decreased (P < 0.01), as did peak power and absolute and
      relative VO2 and VE. Although fitness levels in former elite oarsmen decreased
      each decade, these declines were somewhat arrested by regular aerobic training.
      Body fat increased and metabolic capacity decreased rapidly during the first
      decade, whereas anaerobic capacity decreased more significantly in the second
      decade. Anaerobic capacity diminished at a significantly greater rate than
      aerobic capacity, probably as a result of the aging process and emphasis on
      aerobic training in post-competitive years.

PMID- 8883005
TI  - Physical activity, fitness, and plasma fibrinogen with reference to fibrinogen
      genotypes.
AB  - The relation of daily energy expenditure (EE) and maximal oxygen uptake (VO2max)
      to plasma fibrinogen with reference to DNA polymorphism was analyzed in a random
      sample of men (N = 189), age 50-60. Fibrinogen polymorphism was detected using
      polymerase chain reaction (PCR) and digestion with HindIII and BclI (beta
      fibrinogen), and TaqI (alpha-fibrinogen) restriction enzymes. Mean VO2max was
      29.4 ml.kg-1.min-1 (95%CI 28.5; 30.2) and mean daily EE was 179 kJ.kg-1.d-1 (173;
      186) and were similar in all fibrinogen genotypes. Plasma fibrinogen was 3.26 g.1
      1 (3.18; 3.34) and did not associate with fibrinogen polymorphisms. Both EE and
      VO2max related inversely to fibrinogen level (r = -0.24, P < 0.001). Strongest
      predictors of plasma fibrinogen were VO2max in TaqI 800 bp homozygotes, and EE
      together with smoking in TaqI 900 bp homozygotes. The predictive role of VO2max
      was marginal in the common beta-fibrinogen genotypes, whereas physical activity
      level explained up to 9% of the variance in the less frequent genotypes. These
      data suggest that the association of VO2max and EE with plasma fibrinogen varies
      across the fibrinogen genotypes.

PMID- 8883004
TI  - Determinants of physical activity in obese children assessed by accelerometer and
      self-report.
AB  - Previous research has shown that predictors of activity in adults depend upon the
      method of measurement. This study is designed to assess the predictors of
      activity in a sample of 59 obese children. Activity was measured using self
      reported and TriTrac accelerometer METs. Self-report and TriTrac accelerometer
      measures were moderately correlated, r = 0.46, with the self-reported activity
      (2.3 METs) significantly greater than TriTrac (1.6 METs). Hierarchical regression
      analysis examined the influence of socioeconomic level, body composition,
      fitness, hedonics of child and adult activity behaviors, and decisional balance
      on self-reported and accelerometer-measured activity, controlling for child and
      parent psychopathology. Child and parent psychological symptoms accounted for
      8.3% and 3.4% of the variance in accelerometer and self-reported METs,
      respectively. The model for accelerometer-measured activity showed socioeconomic
      level and parent self-report of activity accounted for 14.8% of the incremental
      variance in child activity. The model for self-report of child activity found
      that child fitness accounted for 23.5% of the incremental variance in child
      activity. These results suggest that the predictors of activity level are
      different based upon the method of measurement, consistent with research in
      adults.

PMID- 8883006
TI  - Subject-related risk factors for sports injuries: a 1-yr prospective study in
      young adults.
AB  - The purpose of this study was to investigate the importance of subject-related
      risk factors for sports injuries, taking exposure time into account. At baseline
      in 182 healthy males and females (27 yr) the following subject-related risk
      factors were assessed: body mass index (BMI), maximal oxygen uptake (direct
      treadmill measurement), seven aspects of neuromotor fitness (MOPER fitness test),
      strength of the hamstring and quadriceps muscles (CYBEX), having sustained a
      sports injury in the 12 months preceding the baseline measurement ("previous
      injury"), and 16 psychological and psychosocial factors (measured with 8
      standard, valid, and reliable questionnaires). For 1 yr, subjects were asked to
      make daily entries on a monthly log concerning all sports activities exceeding an
      intensity of 4 MET and all sustained sport injuries. Completed logs were returned
      by 139 subjects (75 males and 64 females). Fifty-one injuries were registered in
      41 subjects. The overall incidence rate (IR) was 3.7 sports injuries per 1000 h
      of sports participation (95% confidence interval 2.8-4.9). For various
      subcategories, the following IR per 1000 h of sports participation were
      calculated: contact sports IR = 11.0 (95% CI 7.4-16.3); noncontact sports IR =
      2.3% (95% CI 1.6-3.3); competition IR = 13.4 (95% CI 8.7-20.6); and training IR =
      2.8 (95% CI 1.6-5.1). Data were analyzed by stepwise multiple logistic
      regression. The following five variables were independent and significant (P <
      0.05) predictors of risk in sustaining a sport injury: dominance (odds ratio (OR)
      = 1.71; 95% CI = 1.44-2.03), vital exhaustion (OR = 1.85; CI = 1.22-2.86),
      stressful life events (OR = 1.84; 95% CI = 1.10-311); these ORs were calculated
      for an increase of 10% of the range of obtained scores, starting at minimum
      value. For total sporting time, the OR was calculated by taking the group with a
      total sporting time below the median (4050 h) as a reference (OR = 6.87; 95% CI =
      2.09-22.55). For previous injury, subjects that had not sustained a sports injury
      in the 12 months preceding the baseline measurements served as a reference for
      the calculation of the OR (OR = 9.41; 95% CI = 2.80-31.58). These findings
      confirm that both exposure time and previous injury are more important predictors
      of sports injuries than psychological, psychosocial, physiological, and
      anthropometrical factors.

PMID- 8883007
TI  - Cross-sectional and longitudinal uses of isoinertial, isometric, and isokinetic
      dynamometry.
AB  - The purposes of this investigation were to assess whether maximal isoinertial
      (triceps pushdown [TP] and triceps extension [TE]), isometric and isokinetic
      (1.04, 2.08, 3.14, 4.16, and 5.20 rad.s-1) forearm extension strength measures:
      1) presented statistical generality when they were correlated prior to and
      following 4, 8, and 12 wk of resistance training; 2) were similarly affected by
      training; and 3) presented statistical generality when their changes as a
      consequence of training were intercorrelated. Fifteen men (11 experimental and 4
      controls) without a history of resistance training participated in the study.
      Training involved four sets of 8-12 repetitions, each followed by 90-s recovery,
      at 70-75% one repetition maximum (1RM), three times a week, for 12 wk. Training
      incorporated the TP, close-grip bench press, and triceps kickback exercises.
      Prior to and after 4, 8, and 12 wk of training, the intercorrelations among the
      TP, isometric, and isokinetic indices almost always achieved statistical
      generality (i.e., r2 > 0.5). It was concluded that the strength measures
      generally discriminated similarly between subjects. However, the sensitivity of
      the strength measures to the effects of training were dissimilar. While all
      strength indices increased with the training, the timing (isoinertial prior to
      isometric and isokinetic adaptations) and magnitude (TP > TE > isometric >
      isokinetic) of the adaptations varied greatly. None of the intercorrelations
      between changes in the strength indices achieved statistical generality.
      Furthermore, factor (F)-analyses on these changes indicated that in the initial
      and later stages of training, there were three and four discrete factors,
      respectively, accounting for strength development. These factors were thought to
      reflect differential effects of training on the structural, neural (including
      learning), and mechanical mechanisms underpinning each strength index. Possible
      applications of this research design in better understanding strength development
      were also canvassed.

PMID- 8883008
TI  - The effect of positioning on shoulder isokinetic measures in females.
AB  - Weakness of the shoulder rotator musculature is a frequently encountered clinical
      concern in shoulder injuries. However, glenohumeral internal and external
      rotation in the frontal plane (FP) in an abducted position often causes
      impingement of the supraspinatus tendon, whereas similar activity in the scapular
      plane (SP) does not cause impingement. Therefore, the purpose of this study was
      to determine if assessment in two planes affected bilateral internal and external
      peak torque (PT), total work (TW), and average power (AP). Twenty recreationally
      active females (age = 24.9 yr; ht = 163.3 cm; wt = 60.7 kg) were randomly
      assessed in FP and SP for dominant and nondominant side shoulder internal
      rotation (IR) and external rotation (ER) isokinetic strength (Cybex 6000, Lumex
      Inc., Ronkonkoma, NY). Subjects were assessed at 1.047 and 2.094 rad.s-1 in the
      supine position with the shoulder abducted to 90 degrees. Four-way MANOVA
      revealed significant differences for PT, TW, and AP in all measured conditions (P
      < 0.05). These findings indicate that muscular strength is affected by
      positioning in different planes. Due to differences in PT, TW, and AP, it is
      advisable to maintain consistent positioning during assessment to assure
      consistency in the reporting of muscular performance variables.

PMID- 8883009
TI  - Effect of inosine supplementation on aerobic and anaerobic cycling performance.
AB  - Ten competitive male cyclists completed a Wingate Bike Test (WIN), a 30-min self
      paced cycling performance bout (END), and a constant load, supramaximal cycling
      spring (SPN) to fatigue following 5 d of oral supplementation (5,000 mg.day-1)
      with inosine and placebo. Blood samples were obtained prior to and following both
      supplementation periods, and following each cycling test. Uric acid concentration
      was higher (P < 0.05) following supplementation with inosine versus placebo, but
      2,3-DPG concentration was not changed. The data from WIN demonstrate that there
      were no significant differences in peak power (8.5 +/- 0.3 vs 8.4 +/- 0.3 W.kg
      body mass-1), end power (7.0 +/- 0.3 vs 6.9 +/- 0.2 W.kg body mass-1), fatigue
      index (18 +/- 2 vs 18 +/- 2%), total work completed (0.45 +/- 0.02 vs 0.45 +/-
      0.02 kJ.kg body mass-1.30-s-1), and post-test lactate (12.2 +/- 0.5 vs 12.9 +/-
      0.6 mmol.l-1) between the inosine and placebo trials, respectively. No difference
      was present in the total amount of work completed (6.1 +/- 0.3 vs 6.0 +/- 0.3
      kJ.kg body mass-1) or post-test lactate (8.4 +/- 1.0 vs 9.9 +/- 1.3 mmol.l-1)
      during END between the inosine and placebo trials, respectively. Time to fatigue
      was longer (P < 0.05) during SPN for the placebo (109.7 +/- 5.6 s) versus the
      inosine (99.7 +/- 6.9 s) trial, but post-test lactate (14.8 +/- 0.7 vs 14.6 +/-
      0.8 mmol.l-1) was not different between the treatments, respectively. These
      findings demonstrate that prolonged inosine supplementation does not appear to
      improve aerobic performance and short-term power production during cycling and
      may actually have an ergolytic effect under some test conditions.

PMID- 8883010
TI  - Psychological consequences of exercise deprivation in habitual exercisers.
AB  - Psychological consequences of exercise deprivation in habitual exercisers. The
      purpose of this investigation was to evaluate the influence of 3 d of exercise
      deprivation on selected psychological variables. Ten volunteers (4 female and 6
      male) who regularly exercised 6-7 d.wk-1 for at least 45 min at a time
      participated in a 5-d study. Participants completed their regular workout on the
      first day of the study, refrained from physical activity for the next 3 d, and
      then resumed their regular exercise on the 5th d of the study. Participants
      reported to the lab on Monday following their regular workout and completed a
      series of questionnaires, and these same questionnaires were completed at the
      same time of day on the next 4 d. The dependent variables consisted of state and
      trait anxiety (STAI), and tension, depression, anger, vigor, fatigue, confusion,
      and overall mood (POMS). Increases in total mood disturbance, state anxiety,
      tension, depression, and confusion across days were significant (P < 0.05), and
      vigor decreased. The pattern of increasing mood disturbance with exercise
      deprivation was followed by mood improvement to baseline levels when exercise was
      resumed. We concluded that a brief period of exercise deprivation in habitual
      exercisers results in mood disturbance within 24-48 h.

PMID- 8883011
TI  - Ratio scaling of VO2max penalizes women with larger percent body fat, not lean
      body mass.
AB  - VO2max expressed in ml.BM-1.min-1 (BM = body mass) has been shown to unduly
      penalize heavier subjects and instead should be expressed as ml.BM-0.7.min-1.
      Such findings support the "theory of similarity" (TofS) that proposes the BM
      exponent should be 2/3 (0.67). The TofS, however, applies better to lean body
      mass (LBM) that is uninfluenced by fat mass. For young adults, the actual scaling
      exponent of LBM has yet to be satisfactorily determined. We used allometric
      scaling (AS) to scale VO2max by BM and LBM in 94 women (age = 27.4 +/- 6.7 yr, BM
      = 60.3 +/- 8.4 kg). Treadmill VO2max was assessed by indirect calorimetry and LBM
      was determined from hydrostatic weighing. AS yielded the following exponents (+/-
      95% C.I.): BM: 0.61 +/- 0.27, and LBM: 1.04 +/- 0.26. We conclude that VO2max in
      ml.BM-1.min-1 indeed penalizes heavier women, but this penalty applies only to
      those who are heavier because of larger percent body fat, not LBM. If one takes
      the position that excess fatness is undesirable, then from a health and
      performance perspective, expressing VO2max in ml.BM-1.min-1 may provide an
      unbiased and useful expression of VO2max in young women.

PMID- 8883012
TI  - Numerical simulation of a turning alpine ski during recreational skiing.
AB  - While downhill snow skiing, recreational alpine skiers enjoy making turning
      motions with their skis. These motions are mainly induced by skidding, while
      turning by alpine ski racers is made by carving a trace in the snow. In the
      present study we treat the turning motions by recreational alpine skiers. This
      "skidding" turning motion is made possible by centripetal forces acting on the
      ski and skier dynamic motion systems, with these forces arising due to the skier
      placing the ski's longitudinal axis at an angle that is inclined away from the
      velocity vector and edging the ski into the snow. When snow is soft, the edged
      ski creates a snow impacting force, whereas a snow cutting force occurs when it
      is hard. Here, we calculate the former force using a three-dimensional water jet
      analogy, while the latter one using conventional metal cutting theory, after
      which the corresponding equations of motion for each system are derived and
      numerically solved. This methodology enables simulating the curvilinear and
      rotational motion of the ski and skier systems. Resultant simulations
      quantitatively show for the first time that the resultant radius of curvature of
      a ski track while downhill skiing is strongly dependent on the location of the
      ski boot on the ski's longitudinal axis and also on its side-cut (midlength
      taper).

PMID- 8883013
TI  - Betaines and urinary tract infections.

PMID- 8883014
TI  - Biocompatibility of haemodialysis membranes: haemodialysis-related leukotriene B4
      and C4 generation. France.
AB  - The aim of our study was (1) to verify whether haemodialysis (HD) with cuprophane
      (CUP) and polyacrylonitrile (PAN) membranes is associated with the release of
      vasoactive leukotriene (LT) C4 and chemotactic LTB4 and (2) to analyse the
      respective roles of lipoxygenase and cyclo-oxygenase metabolites of arachidonic
      acid in membrane bio-incompatibility. The investigation was performed in 10
      uremic patients using hollow-fibre dialysers and dialysed successively, in random
      order, with CUP and PAN membranes. The arterial and venous (from dialyser) blood
      was sampled for the measurement of biochemical parameters, plasma LTC4, LTB4 and
      prostaglandins (PG) 6-keto-F1 alpha, E2, F2 alpha and thromboxane B2 before and
      after 15, 30 and 240 min of HD. Eicosanoids were measured by RIA after prior
      extraction and HPLC separation. RESULTS: CUP HD was associated with a marked
      early leukopenia and a delayed decrease in blood pO2. Simultaneously, plasma LTB4
      and LTC4 increased significantly in arterial blood after 30 min of HD and in
      venous blood at the end of session of 240 min. Cyclo-oxygenase metabolites
      increased as well, but nonsignificantly, with a maximum at the end of HD. PAN HD
      did not significantly change white blood cell count, pO2, or plasma eicosanoid
      levels. CONCLUSION: CUP membranes stimulate the release of proinflammatory and
      vasoactive LTB4 and LTC4. PAN membrane haemodialysis is without such side
      effects. The release of LTs may be an additional valuable marker of membrane
      bioincompatibility.

PMID- 8883015
TI  - A study on regulating factors of plasma refilling during hemodialysis.
AB  - Hypotension is frequently encountered during hemodialysis (HD). One of the main
      factors of the HD-induced hypotension is acute reduction of circulating plasma
      volume by water removal, which is induced by the poor plasma refilling from the
      extravascular space into vessels. The determinants of plasma refilling, however,
      have not been clearly identified. Recently, we devised a mathematical model of
      water transport in HD patients, which can estimate the plasma-refilling
      coefficient (Kr) during HD. In the present study, we evaluated the factors
      determining plasma refilling by using this model. In 13 patients undergoing
      regular HD, the changes of Kr during HD were calculated from the model. Levels of
      ANP, cGMP, cAMP, endothelin, angiotensin II and vasopressin were measured before
      and after HD. Kr fell from 750.4 +/- 558.0 to 112.8 +/- 81.9 ml/mm Hg/h during
      HD. The rate of water removal during HD showed no significant correlation with
      the changes of Kr. Among the hormones and nucleotides measured here, plasma ANP
      level and cGMP were significantly correlated with Kr (r = 0.78, p < 001 and r =
      0.62, p < 0.01, respectively). Our findings suggest that severe reduction in the
      level of serum ANP during HD, which is induced by water removal, plays some role
      in HD-induced hypotension through the attenuation of plasma refilling in HD
      patients.

PMID- 8883016
TI  - Biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid
      compared to a 2.27% glucose-based peritoneal dialysis fluid.
AB  - The biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid
      (AA-PDF) was compared to that of a 2.27% glucose-based peritoneal dialysis fluid
      (G-PDF). Peritoneal macrophages (PMO), isolated from the peritoneal dialysis (PD)
      effluents of 10 chronic ambulatory PD patients, were tested for their
      phagocytosis capacity and peak chemiluminescence response. A subset of PMO was
      cultured for 24 h with and without lipopolysaccharide (LPS) to study the release
      of interleukin-1 beta (IL-1 beta) and 8 (IL-8). As control, the interleukin
      release by blood monocytes of healthy donors was tested. The opsonic activity of
      the PD effluent was tested as well. Compared to PMO isolated from G-PDF, PMO from
      AA-PDF showed a significantly better phagocytosis capacity. There was no
      difference in the peak chemiluminescence response between PMO from AA-PDF and G
      PDF. The release of IL-1 beta by unstimulated PMO isolated from the two fluids
      did not differ. Compared to control monocytes, however, PMO from both fluids
      showed a considerable spontaneous release of IL-1 beta. When stimulated with LPS,
      IL-1 beta production by PMO from G-PDF exceeded that of PMO from AA-PDF (p <
      0.002). The release of IL-8 by PMO from G-PDF was significantly higher in
      comparison with PMO from AA-PDF, both spontaneously and after stimulation with
      LPS (p < 0.02). The opsonic activity of undiluted and to 75% diluted effluents
      was significantly higher for G-PDF than for AA-PDF (p < 0.01). Thus, compared to
      the regularly used G-PDF, the phagocytosis capacity as measure for PMO function
      seems to be better preserved after in vivo exposure to AA-PDF. In addition, the
      higher release of IL-1 beta and IL-8 by PMO isolated from G-PDF suggests a
      stronger intra-abdominal activation of PMO, with G-PDF acting as a chemical
      inflammatory agent. Whether the lower opsonic activity of the AA-PDF is more
      important for biocompatibility than the other parameters is not clear. Therefore,
      it is concluded that, although macrophage function is better preserved, it is not
      proven that the 1.1% AA-PDF studied has an improved biocompatibility compared to
      2.27% G-PDF.

PMID- 8883017
TI  - Effect of long-term low-dose aluminum-containing agents on hemoglobin synthesis
      in patients with chronic renal insufficiency.
AB  - To investigate the possible toxic effects of long-term low-dose exposure to A1
      containing agents in 55 patients with chronic renal insufficiency (CRI), 37
      patients received A1(OH)3 1 tablet 3 times per day (about 302 mg/day of elemental
      A1) for 3 months and another 18 were used as a control group. The hematological,
      iron status and A1 data were measured before and after the study. CRI patients
      who had ingested A1-containing agents for 3 months had significant decreases in
      hematological parameters and increases in serum A1 and daily urinary A1
      excretion. Serum ferritin negatively correlated with serum A1 (r = -0.586, p <
      0.0005), and hemoglobin (Hb) positively correlated with renal A1 clearance (r =
      0.573, p < 0.0005) and logarithmic transformation of serum A1 (r = -0.437, p <
      0.01) in these patients, despite no significant correlations between initially
      basal hematological and A1 parameters. But there were no significant differences
      between variables of A1 and hematological parameters before and after 3 months of
      follow-up in the control group. All factors correlating with Hb were measured
      with stepwise regression analysis; renal A1 clearance, creatinine clearance (Ccr)
      and serum iron were the most significant correlation factors with Hb. After Ccr
      and serum iron had been adjusted, Hb (b = 0.069 +/- 0.02; p < 0.05) still
      positively correlated with renal A1 clearance. Comparing patients who had reduced
      Hb (at least 0.5 g/dl) and those who did not, the response group had a lower
      basal (Ccr, a higher serum A1 and a lower renal A1 clearance after A1 loading for
      3 months. In conclusion, A1 does play a role in the significant reduction of Hb
      and hematocrit in CRI patients after A1 loading for 3 months, and patients with a
      lower Ccr may easily develop A1-induced hematologically toxic effects. A1
      containing agents should be used with care in long-term therapies of CRI
      patients.

PMID- 8883018
TI  - Lipocortin-1 inhibits proliferation of cultured human mesangial cells.
AB  - Lipocortin-1, a 37-kDa member of the annexin family of proteins, originally
      evoked interest as one of the second messengers for the anti-inflammatory actions
      of glucocorticoids. Studies showed that glucocorticoids inhibited the
      proliferation of various cell types and lipocortin-1 mediated growth inhibition
      of glucocorticoids in a human lung adenocarcinoma cell line. The presence of
      specific lipocortin-1-binding sites (receptor-like molecules) on monocytic cells
      has been demonstrated. This study was performed to evaluate the effects of
      hydrocortisone and recombinant human lipocortin-1 on cultured human mesangial
      cells (CHMC), and the effects of anti-lipocortin-1 antibody on the hydrocortisone
      induced inhibition of CHMC proliferation. The existence of specific binding sites
      for lipocortin-1 was also investigated. Lipocortin-1 inhibited CHMC proliferation
      in a dose-dependent manner as determined by [3H]thymidine uptake and cell count.
      Growth of CHMC was inhibited to 18% of the control in the presence of 5
      micrograms/ml of lipocortin-1. Similar growth-inhibitory activity by lipocortin-1
      was observed in CHMC activated by platelet-derived growth factor. Hydrocortisone
      also inhibited cell proliferation in a dose-dependent manner. One to 5,000
      dilution of anti-lipocortin-1 antibody reversed hydrocortisone-induced inhibition
      of CHMC proliferation partially, whereas concentrations over 1:1,000 reversed the
      inhibition completely. Flow cytometry analysis as well as indirect
      immunofluorescent microscopy revealed specific binding sites on the surface of
      CHMC. These results support the hypothesis that corticosteroids act by inducing
      CHMC to synthesize or secrete lipocortin-1, and that lipocortin-1 generates
      proliferation-suppressive signal(s) through specific binding sites on CHMC.

PMID- 8883019
TI  - The treatment of chronic hemodialysis vascular access by directional atherectomy.
AB  - Directional atherectomy (DA) was developed as a new therapeutic modality for
      coronary artery disease. For the past 3 years, we have applied DA intervention to
      vascular access failure with either poor blood flow rate or high venous pressure.
      DA intervention was performed on 27 lesions of 16 hemodialyzed patients. A
      reduction of stenosis to less than 20% of that before treatment was judged a
      technical success, and the rate of technical success was 84%. All patients showed
      adequate blood flow rates after DA intervention, indicating initial success.
      Although restenotic events occurred frequently, repeated DA interventions could
      be performed successfully. The patency rate at 1 month after DA intervention was
      100%, at 3 months 93%, at 6 months 92% and at 12 months 75%. The short-term
      patency rate of DA was more satisfactory than the results of percutaneous
      transluminal angioplasty as reported by several investigators. Regarding the site
      of stenosis, restenotic events were relatively fewer in the lesions occurring at
      the native vein compared to those at graft-venous anastomotic sites. Eccentric
      type stenosis was also associated with fewer restenotic events than
      circumferential-type stenosis. These results suggest that eccentric-type stenosis
      at the native vein is the most suitable lesion for the application of DA
      intervention in terms of long-term patency. As no severe complications occurred
      after DA intervention, this would appear to be a useful therapeutic modality for
      the correction of vascular access failure.

PMID- 8883020
TI  - 5-year follow-up of patients successfully transplanted after immunoadsorption to
      remove anti-HLA antibodies.
AB  - The function of renal allografts in patients who had received pretransplant
      immunoadsorption in order to remove cytotoxic anti-HLA antibodies was studied. We
      reviewed 6 patients who received a graft which functioned beyond 3 months; the
      mean follow-up period was 76 (range 62-89) months. Two grafts have been lost from
      chronic rejection, at 12 and 62 months, respectively. The mean plasma creatinine
      levels at 1 and 5 years were 169 (range 143-211) mumol/l and 155 (range 92-235)
      mumol/l, respectively (1.91, range 1.62-2.39, mg/dl and 1.75, range 1.04-2.66
      mg/dl, respectively). The major source of morbidity during long-term follow-up
      has been the occurrence of renal artery stenosis in 5 patient and renal vein
      stenosis in 1. In conclusion, the 5-year graft survival and function was good in
      patients who received immunoadsorption and whose grafts survived beyond the first
      3 months after transplantation.

PMID- 8883021
TI  - Study of kidney rejection following simultaneous kidney-pancreas transplantation.
AB  - Simultaneous kidney-pancreas (SKP) transplantation is associated with increased
      risk of kidney rejection (KR) due to an unknown mechanism. The aim of this study
      is to analyze the characteristics of KR in 44 SKP transplantations under
      quadruple immunosuppressive therapy and to evaluate the response to treatment and
      its effect on renal allograft survival and renal function. The mean follow-up was
      25 +/- 14 months. Seventy-seven percent of the patients (34 of 44) presented an
      acute renal allograft rejection. Sixty-six percent (29 of 44) had one rejection
      episode and 11% (5 of 4) 2 episodes. KR was early (85% in the first month after
      transplantation), intense (3.7-fold increase in creatinine) and had great
      clinical features. Twenty-eight percent of the patients had an early relapse
      during the first month after treatment. KR did not affect the survival of the
      renal allograft in the short-term (1 and 2 years). Overall, 62% were
      corticosensitive (CS) and the remaining 38% were corticoresistant (CR). The group
      with an isolated rejection without relapse was CS in 69% of the cases, achieved
      complete remission in 73% and renal function was not affected at 1 and 2 years
      [115 +/- 26 mumol/l (1.3 +/- 0.3 mg/dl) and 150 +/- 53 mumol/l (1.7 +/- 0.6
      mg/dl)] in comparison with the group without rejection [97 +/- 18 mumol/l (1.1 +/
      0.2 mg/dl) and 115 +/- 35 mumol/l (1.3 +/- 0.4 mg/dl); p = NS]. On the other
      hand, the group with an early relapse of the first rejection and the group with
      two rejections were principally CR (62 and 60%, respectively), had partial
      remission with treatment (50 and 60%) and had worse renal function at 1 and 2
      years [212 +/- 71 mumol/l (2.4 +/- 0.8 mg/dl) and 221 +/- 53 mumol/l (2.5 +/- 0.6
      mg/dl)] than in the group with isolated KR (p < 0.05 and p < 0.001). In
      conclusion, despite intense immunosuppressive treatment, the frequency of
      rejection of a renal allograft in SKP is high. The response to treatment is
      satisfactory and does not affect the survival of the allograft in the short-term.
      However, multiple episodes or early relapse of rejection are associated with
      higher creatinine levels.

PMID- 8883022
TI  - Glomerular hypertrophy in relapsing minimal change nephropathy.
AB  - Clincopathological and morphometric analysis of glomerular hypertrophy was
      conducted using biopsies from 89 patients with minimal change nephrotic syndrome
      (MCNS). Of the 80 patients, in 69 with complete remission and in 20 with one or
      more relapses, various clinical and morphometric parameters were compared to 15
      normal controls. Proteinuria was more severe and serum creatinine (Cr)
      concentration significantly higher in patients with relapse of proteinuria. The
      morphometric analysis showed that the sizes of (1) glomerular tufts and (2)
      glomerular capillaries were significantly larger in patients in the relapse group
      than in the remission or control groups, but no difference in the size of
      Bowman's capsule was found between the two MCNS subgroups. The intertubular
      capillaries were narrower in patients who failed to reach prompt complete
      remission. A negative correlation between intra- and extraglomerular capillary
      size was evident (r = -0.83, p < 0.001). A definitive correlation was detected
      between the circumference of glomerular capillary loops and the degree of
      proteinuria (r = 0.89, p < 0.001). The mean tubulocapillary diffusion distance
      was significantly longer in biopsies of the patients in relapse and showed a
      close significant correlation with serum Cr level (r = -0.87, p < 0.001) and
      intertubular capillary size (r = -0.87, p < 0.001). These data suggest that extra
      and intraglomerular hemodynamic alterations in MCNS lead to glomerular
      hypertrophy, and dilatation of the glomerular capillary loop plays a key role in
      the relapse of MCNS.

PMID- 8883023
TI  - Accumulation of indoxyl-beta-D-glucuronide in uremic serum: suppression of its
      production by oral sorbent and efficient removal by hemodialysis.
AB  - We identified and quantified indoxyl-beta-D-glucuronide in uremic serum and urine
      to determine the metabolism of indoles including indoxyl sulfate in uremic
      patients. Serum levels of indoxyl-beta-D-glucuronide were markedly increased in
      undialyzed uremic patients, in patients on hemodialysis, and in patients on
      continuous ambulatory peritoneal dialysis. Urinary excretion of indoxyl-beta-D
      glucuronide was also increased in undialyzed uremic patients. Urinary indoxyl
      beta-D-glucuronide was significantly correlated with serum indoxyl sulfate,
      indicating that a high serum level of indoxyl sulfate leads to the enhanced
      synthesis of indoxyl-beta-D-glucuronide. Oral sorbent (AST-120) administration
      markedly decreased the serum and urine levels of indoxyl-beta-D-glucuronide as
      well as indoxyl sulfate in the undialyzed uremic patients. Serum indoxyl-beta-D
      glucuronide could be efficiently removed by hemodialysis despite its high protein
      binding ratio of about 50%. In conclusion, the serum level of indoxyl-beta-D
      glucuronide increases in uremic patients due to renal insufficiency and its
      increased production. The production of indoxyl-beta-D-glucuronide can be
      suppressed by oral sorbent treatment, and serum indoxyl-beta-D-glucuronide can be
      efficiently removed by hemodialysis.

PMID- 8883024
TI  - Increased excretion of tumor necrosis factor alpha and interleukin 1 beta in
      urine from patients with IgA nephropathy and Schonlein-Henoch purpura.
AB  - Urinary proteins (5 mg/ml) collected from a group of 16 patients including 13
      with IgA nephropathy and 3 with Schonlein-Henoch purpura (SHP) and from a control
      group consisting of 6 patients with diabetic nephropathy, 5 patients with
      hypertensive nephrosclerosis, and 5 healthy hospital staff members were studied
      for the contents of interleukins (IL) 1 beta, 2, 4, 6, and 12 and tumor necrosis
      factor alpha (TNF-alpha). Eleven patient with IgA nephropathy or SHP (11/16) but
      only 1 of the controls (1/16) had TNF-alpha activity in urinary proteins (p <
      0.01). The IL-1 beta activity exhibited a similar tendency but to a lesser extent
      (10 of 16 patients with IgA nephropathy or SHP vs. 2 of 16 with other conditions,
      p < 0.05). Conversely, the detection rates of IL-2, IL-4, and IL-6 in both groups
      were not significantly different. IL-12 was not found in any of the samples from
      both groups. Sera and nonpurified urine samples from the same individuals were
      also measured for cytokines. IL-1 beta, IL-2, IL-4, and IL-12 were absent in all
      these samples, but TNF-alpha was found in four of the serum samples from patients
      with IgA nephropathy. Urinary proteins (2 mg/ml) were analyzed using sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, whereby peptides of 52, 49,
      45, 34, 30, and 11 kD could be demonstrated in the patients with IgA nephropathy
      or SHP. Urinary proteins (200 micrograms/ml from patients with IgA nephropathy or
      SHP exerted a mitogen-like effect on the normal human mononuclear cells, as
      demonstrated by 3H-thymidine incorporation. In addition, these urinary proteins
      (400 micrograms/ml) enhanced the proliferative activity of the cultured rat
      glomerular mesangial cells. The exaggerated proliferation of rat glomerular
      mesangial cells exerted by urine proteins from 2 patients with active disease was
      markedly suppressed after treatment with glucocorticoids/cyclophosphamide. These
      results suggest that patients with IgA nephropathy or SHP can excrete excessive
      amounts of TNF-alpha and IL-1 beta in the urine. The inconsistent presence of
      these two cytokines in urine and serum may indicate that they can be produced
      locally and that they are implicated in the development of mesangial inflammation
      and glomerular damage.

PMID- 8883025
TI  - Long-term effects of intravenous 1 alpha (OH)D3 combined with CaCO3 and low
      calcium dialysis on secondary hyperparathyroidism and biochemical bone markers in
      patients on chronic hemodialysis.
AB  - The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1
      alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l)
      on plasma (p) parathyroid hormone (PTH) and biochemical bone markers
      (osteocalcin, alkaline phosphatase, procollagen type 1 c-terminal extension
      peptide) were examined in 54 patients on chronic hemodialysis with either normal
      or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered
      intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood
      samples were obtained 1 week before the start of treatment and then every 2nd
      week. 20 patients with initially normal PTH levels (23.5 +/- 4.17 pg/ml) and 34
      patients with initially elevated PTH levels (301 +/- 45 pg/ml) were followed for
      up to 88 weeks. The present investigation: demonstrated: (1) 'Low-calcium
      hemodialysis' (1.25 mmol/l) made it possible to use larger doses of CaCO3 and to
      reduce the doses of an aluminium-containing oral phosphate binder. A decrease in
      p-Ca2+ during dialysis was induced, and special care had to focus on the
      compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism.
      (2) The combination of 'low-calcium hemodialysis', CaCO3, and pulse intravenous 1
      alpha (OH)D3 prevented the development of secondary hyperparathyroidism in
      patients with normal PTH levels and induced a long-term suppression of p-PTH (106
      +/- 25 pg/ml, 88 weeks) in the patients with secondary hyperparathyroidism. By
      careful monitoring, severe hypercalcemia and hyperphosphatemia were avoided.
      There were no indications, clinically or biochemically, of development of
      adynamic bone disease. (3) Bone lesions were healed and a decrease of the bone
      mineral content in lumbar spine and femoral neck of patients with both normal and
      elevated PTH levels prevented. (4) The present results may suggest that PTH might
      be of influence on that regulation of procollagen type 1 c-terminal extension
      peptide.

PMID- 8883026
TI  - Hemodialysis immediately after acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) is common in patients who have end-stage renal
      disease. However, the prudent interval after AMI until resuming hemodialysis is
      unknown. Also incidence and severity of intradialytic morbid events during the
      initial dialysis treatment after AMI have not been determined. We conducted a
      retrospective analysis of the course of hemodialyses performed immediately after
      AMI in 13 maintenance hemodialysis patients (group 1) hospitalized with AMI over
      the 5-year period 1988-1992. For comparison, the incidence of intradialytic
      morbid events (hypotension--systolic blood pressure < 90 or diastolic blood
      pressure < 60 mm Hg or a fall in systolic or diastolic blood pressure of > 30 mm
      Hg--with and without symptoms, arrhythmias, and unplanned termination of
      hemodialysis was extracted from the charts of 9 maintenance hemodialysis patients
      (group 2) admitted during the same period with angina but no AMI, and in 13
      stable ambulatory hemodialysis patients (group 3) dialyzed during the same period
      who had no evidence of heart disease. Patients in groups 1 and 2 were sorted by
      time interval from onset of chest pain to initiation of hemodialysis (< 12, 12
      24, and > 24 h). In group 1, we examined the relationship of anatomic location of
      AMI, number of antihypertensive medications, predialysis left ventricular
      systolic ejection fraction, and various other clinical and laboratory parameters
      to the incidence intradialytic morbid events. The mean (+/- SD) age of the study
      subjects was 67 +/- 7.5 years in group 1, 57 +/- 3.7 in group 2, and 60 +/- 11
      years in group 3 (p = 0.6). Arrhythmias and early termination of dialysis did not
      occur in any patient. Intradialytic hypotension (IDH) was recorded in 5 (38%) of
      13 patients in group 1, in 3 (33%) of 9 in group 2, and in 2 (15%) of 13 patients
      in group 3 (p = 0.47). 4 (80%) of 5 patients in group 1 had multiple episodes of
      IDH. There were 0.92 +/- 1.4 episodes of IDH per patient in group 1 as compared
      with a rate of 0.44 +/- 0.68 per patient in group 2, and of 0.15 +/- 0.36 per
      patient in group 3 (p = 0.2). IDH responded to 0.9% normal saline replacement in
      all cases. Group 1 patients who had IDH (n = 5) were older (68 +/- 3 vs. 58 +/- 7
      years, p = 0.01), had a lower diastolic blood pressure at the start of
      hemodialysis (59 +/- 13 vs. 83 +/- 13 mm Hg; p = 0.01), had a lower post-AMI left
      ventricular systolic ejection fraction (42 +/- 19 vs. 62 +/- 10%; p = 0.04), and
      also had a lower predialysis serum albumin level (3.6 +/- 0.4 vs. 4.1 +/- 0.4
      g/dl; p = 0.09) than those who did not have IDH (n = 8). All 5 group 1 patients
      who had IDH (100%) had had prior AMI as compared with 2 (25%) of 8 of those who
      did not have IDH (p = 0.02). AMI involved the inferior myocardial wall in more (4
      of 5; 80%) of the group 1 patients who had IDH as compared with those who did not
      have IDH (2 of 8; 25%; odds ratio = 9.5; p = 0.08; 95% confidence interval = 0.7
      341.0). In group 1 patients, the time from onset of chest pain to hemodialysis
      did not affect the risk of IDH (p = 0.4). We conclude that a low diastolic blood
      pressure at onset of hemodialysis prior myocardial infarction, inferior
      myocardial wall involvement, advanced age, and a low predialysis serum albumin
      level are risk factors for the development of hypotension during the first
      hemodialysis session after AMI.

PMID- 8883027
TI  - Urinary leucine aminopeptidase is a more sensitive indicator of early renal
      damage in non-insulin-dependent diabetics than microalbuminuria.
AB  - We measured urinary activity of leucine aminopeptidase (EC 3.4.11.2) and
      creatinine concentrations (Cr, in mmol) in samples of second morning urine from
      25 healthy subjects and 59 non-insulin-dependent diabetic (NIDD) subjects. If
      NIDD subjects are grouped according to their Alb/Cr ratio into normoalbuminuria
      (group A, Alb/Cr < 2.8 mg/mmol), microalbuminuria (group B, Alb/Cr 2.8-26.8
      mg/mmol), and macroalbuminuria (group C, Alb/Cr > 26.8 mg/mmol), LAP/Cr ratios in
      all three groups exceeded those for healthy age-matched controls. Moreover, this
      ratio was higher in group B than in group A. The value for LAP/Cr was clearly
      abnormal (i.e., exceeded the upper limit of normal, log normal + 2 SD, found in
      healthy subjects) in 44% of group A. In the first 10-year period Of NIDD,
      prevalance of abnormal LAP/Cr ratio was 61.3%, whereas that of microalbuminuria
      was 35.5%. We have also found a LAP/Cr ratio abnormality of 91% in group B.
      Evidently, LAP/Cr may be increased early in NIDD subjects and be a more sensitive
      predictor of incipient nephropathy than microalbuminuria.

PMID- 8883028
TI  - Na+/H+ exchange in patients with mild chronic renal failure.
AB  - Cytosolic pH (pHi) and Na+/H+ exchange activity were measured in lymphocytes from
      22 patients with mild chronic renal failure, and 21 age- and sex-matched
      normotensive healthy control subjects using the fluorescent dye technique. The
      basal pHi in resting lymphocytes was not significantly different in both groups
      tested (control, pHi 7.18 +/- 0.04; patients with mild chronic renal failure,
      7.17 +/- 0.05). The initial rate of pHi recovery immediately after intracellular
      acidification with 100 mmol/l propionic acid, representing the maximum Na+/H+
      exchange activity, was significantly higher in lymphocytes from patients with
      mild chronic renal failure (7.10 +/- 0.52 dpHi/s, mean +/- SEM) when compared
      with control subjects (5.42 +/- 0.47 dpHi/s; p < 0.05). No significant
      correlation between Na+/H+ exchange activity and blood pressure could be obtained
      in patients with mild chronic renal failure. Furthermore, there was no
      relationship of Na+/H+ exchange activity to cytosolic pH or extracellular pH. It
      is concluded that an enhanced Na+/H+ exchange activity can be detected in
      patients with mild chronic renal failure and may not be related to the
      significant abnormalities of electrolyte and acid-base metabolism commonly
      observed in patients with end-stage renal failure or on hemodialysis.

PMID- 8883029
TI  - Serum angiotensin-converting enzyme activity in patients with endemic
      nephropathy.
AB  - Serum angiotensin-converting enzyme was measured in 60 patients with endemic
      nephropathy and in 30 healthy individuals. According to the arterial blood
      pressure, the patients with endemic nephropathy were further divided into groups
      with arterial hypertension (n = 30) and without arterial hypertension (n = 30).
      The activity of angiotensin-converting enzyme was determined by a
      spectrophotometric method using hippuryl-l-histidyl-l-leucine as a substrate. The
      serum activity of angiotensin-converting enzyme was significantly increased in
      the patients with endemic nephropathy (28.51 +/- 1.64 U/l) as compared with
      healthy individuals (20.83 +/- 1.33 U/l). The level of the enzyme was further
      increased if the endemic nephropathy was accompanied by arterial hypertension
      (37.09 +/- 1.45 U/l). The possible mechanisms of the increase in the angiotensin
      converting enzyme activity are discussed.

PMID- 8883030
TI  - Ultrasonic tissue characterization of renal cell carcinoma tissue.
AB  - The purpose of this study was to characterize renal cell carcinoma tissue by the
      measurement of microacoustic properties. A scanning acoustic microscope system
      operating in the frequency range of 100-200 MHz was employed and the attenuation
      constant and sound speed were measured on the two-dimensional distribution. The
      values of attenuation constant and sound speed were lower in both kinds of cancer
      cells than those in normal kidney, although a significant difference was not
      found between the clear cell and granular cell. Also, both acoustic parameters of
      cancer cells were significantly lower than those in hemorrhage and fibrosis.
      These data suggest that the elasticity of renal cell carcinoma tissue may be
      lower than that of normal kidney. Moreover, the high intensity echo in clinical
      echography may be related to the heterogeneity of the microacoustic field in the
      carcinoma tissue.

PMID- 8883031
TI  - Prevention of posttransplant peptic ulcer by misoprostol.
AB  - Misoprostol is effective in protecting the gastric mucosa against various
      injuries (cytoprotection), but its role in preventing peptic ulcer disease (PUD)
      is controversial. Therefore, this study was designed to evaluate the effect of
      misoprostol on preventing posttransplant PUD. 87 patients undergoing kidney
      transplantation (KT) were randomly separated into three groups according to the
      antiulcer regimen. Group 1 (n = 28) received antacid and ranitidine; group 2 (n =
      34) received antacid, ranitidine, and bismuth (De Nol), and group 3 (n = 25)
      received antacid, ranitidine, and misprostol (prostaglandin E1). Antiulcer drugs
      started 1 week before KT and were continued after surgery. A pretransplant
      gastrofibroscopy was performed 1 month before KT, and a follow-up gastroscopy was
      performed 2-3 weeks after KT. The incidence of peptic ulcer in groups 1 and 2 was
      50.0% (14/28) and 35.3% (12/34), respectively (p > 0.05 groups 1 vs. 2). In group
      3, 12.0% (3/25) of the patients showed PUD (p < 0.05 when compared with group 1
      or 2). The known risk factors of posttransplant PUD were not significantly
      different in three groups, but the KT recipients of groups 1 and 2 had 7.8 times
      the risk of PUD when compared with group 3. In conclusion, the antiulcer regimen
      including misoprostol is more effective than ranitidine or bismuth in preventing
      posttransplant PUD, and the antiulcer effect of misoprostol seems to be related
      to the cytoprotective effect of the drug.

PMID- 8883032
TI  - Renal effects of acute and chronic nitric oxide inhibition in experimental
      diabetes.
AB  - We investigated whether nitric oxide (NO) contributes to glomerular
      hyperfiltration in experimental diabetes. Thirty-five adult male Munich-Wistar
      streptozocin-diabetic rats and 39 nondiabetic controls were distributed among 4
      groups: C, normal control; C + L-NAME, controls receiving the NO inhibitor N
      omega-nitro-L-arginine methyl ester (L-NAME), 40 mg/dl in drinking water; DM,
      diabetic rats; DM + L-NAME, diabetic rats receiving L-NAME, 15 mg/dl in drinking
      water. After 1 month of treatment, the DM + L-NAME group exhibited renal
      vasoconstriction and lacked hyperfiltration. Acute administration of L-NAME, 2.5
      mg/kg, depressed the glomerular filtration rate and promoted renal
      vasoconstriction to a much greater extent in the DM than in the C group. Acute
      administration of endothelin 1 (600 ng/kg, bolus) or angiotensin II (25
      micrograms/kg/min, continuous infusion) exerted similar hemodynamic effects in
      the C and DM groups, suggesting that the enhanced response of DM to L-NAME
      reflected specific sensitivity to NO inhibition. Urinary excretion of nitrites
      and nitrates was fourfold higher in DM compared to C. These results support the
      notion that augmented NO production may contribute to renal hyperfiltration and
      hyperperfusion in diabetes.

PMID- 8883033
TI  - Chronic inhibition of nitric oxide synthase in Heymann nephritis.
AB  - Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the
      course of Heymann nephritis was examined in rats. L-NG-nitroarginine-methylester
      (L-NAME, 10 mg/100 ml in the drinking water for 12 weeks) was used as an
      inhibitor of NO synthase. Urinary excretion of guanosine 3',5'-cyclic
      monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate
      of NO activity. Rats were divided into the following groups: control, nephritis,
      L-NAME, and nephritis-L-NAME. Urinary cGMP excretion was lower in the nephritis
      group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with
      controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the
      nephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05. L-NAME
      treatment alone did not have any effect on plasma ANP levels. Blood pressure rose
      progressively in all L-NAME-treated rats. Most marked albuminuria developed in
      the nephritis-L-NAME group. No differences in the immunohistological findings
      were observed between the nephritis and the nephritis-L-NAME groups. NO synthase
      inhibition causes hypertension and aggravates albuminuria in chronic nephritis.
      Moreover, nephritis itself may decrease then production of cGMP either as a
      consequence of blunted NO activity or, in addition, because of ANP resistance. It
      appears that NO synthase inhibition does not change the immunological course of
      Heymann nephritis but rather the increased hemodynamic load makes the course of
      nephritis worse.

PMID- 8883034
TI  - Calcium entry stimulated by swelling of Madin-Darby canine kidney cells.
AB  - Cell swelling in Madin-Darby canine kidney (MDCK) cells by reduction of
      extracellular osmolarity (omission of 70 ad 150 mmol/l mannitol, respectively)
      leads to the activation of anion of channels and Ca2+ sensitive K+ channels. The
      K+ channel activation leads to an initial transient hyperpolarization of the cell
      membrane potential (PD) followed by a sustained depolarization due to activation
      of anion channels. The present study elucidates the role of intracellular calcium
      (Ca2+i) in regulatory cell volume decrease (RVD) of MDCK cells. While reduction
      of extracellular osmolarity by omitting 70 mmol/l mannitol did not lead to a
      detectable change in Ca2+i, severe cell swelling by omitting 150 mmol/l mannitol
      led to a transient rise in Ca2+i. PD changes, on the other hand, were not
      different under either condition. In addition, the response of PD to cell
      swelling was not altered by treatment of the cells with 12-O-tetradecanoylphorbol
      13-acetate diester, pertussis toxin or cholera toxin. In the nominal absence of
      extracellular Ca2+, reduction of extracellular osmolarity did not lead to an
      increase in Ca2+i and no initial transient hyperpolarization was observed,
      whereas addition of 10 mumol/l ATP still led to a significant hyperpolarization.
      Omission of extracellular Ca2+ was followed by a strong decrease in cell membrane
      resistance (Rm) due to activation of a depolarizing cation conductance.
      Subsequent readdition of Ca2+ caused a marked increase in Ca2+i due to Ca2+
      influx. This Ca2+ entry was further stimulated by cell swelling. RVD was
      significantly blunted in the absence of extracellular Ca2+. The results suggest
      that cell swelling stimulates a Ca2+-permeable pathway in the cell membrane
      favoring Ca2+ entry into the cell with subsequent activation of Ca2+-sensitive K+
      channels.

PMID- 8883035
TI  - Protective action of ulinastatin against cisplatin nephrotoxicity in mice and its
      effect on the lysosomal fragility.
AB  - The development of azotemia after cisplatin injection in mice was inhibited by
      ulinastatin treatment in a dose-dependent manner. Reduction in creatinine
      clearance and elevation in fractional excretion of sodium in mice receiving
      cisplatin was ameliorated by ulinastatin administration. Epithelial necrosis and
      hyaline cast formation in the proximal tubule were also suppressed. Ulinastatin
      showed no influence on the kidney platinum level after cisplatin injection. In
      LLC-PK1 cells, addition of ulinastatin to the incubation medium markedly reduced
      the release of N-acetyl-beta-D-glucosaminidase, on of the lysosomal enzymes,
      during hypotonic treatment only when cells were damaged with cisplatin. On the
      other hand, ulinastatin showed no effect on the elevation of malondialdehyde
      concentration in the murine kidney cortical slices after the treatment with
      cisplatin. These results indicate that ulinastatin has a protective effect
      against cisplatin nephrotoxicity, and its prevention of the increase in lysosomal
      fragility is a probable mechanism involved in the renal protection.

PMID- 8883036
TI  - Renal hemodynamic response to gradated ureter obstruction in the pig.
AB  - In anesthetized pigs with ultrasonic flow probes mounted on each renal artery and
      catheters placed in the abdominal aorta and both renal veins, renal blood flow
      (RBF), glomerular filtration rate (GFR) and filtration fraction (FF) were
      investigated during stepwise unilateral ureteral obstruction. Elevation of the
      ureteral pressure in steps of 10 mm Hg to a maximum of 80 mm Hg decreased
      ipsilateral RBF by 45 +/- 3% from 300 +/- 25 to 168 +/- 20 ml/min (p < 0.01).
      Contralateral RBF did not change significantly. The mean arterial pressure ws
      constant during the experimental procedures, suggesting that the decrease of RBF
      was due to a significant increase in ipsilateral renal vascular resistance.
      Concomitantly with these changes ipsilateral GFR was reduced by 75% from 40 +/- 2
      to 10 +/- 3 ml/min. In the contralateral kidney, GFR was unchanged during the
      experiment. The renal extraction of 51Cr-EDTA equal to FF increased temporarily
      from 0.202 +/- 0.013 at start to 0.239 +/- 0.015 (p < 0.05) at 20 mm Hg in the
      ipsilateral kidney, whereafter it was dramatically reduced to 0.090 +/- 0.024 at
      maximum pressure. In addition, renal tubular handling of salt and water in the
      contralateral kidney were investigated using the lithium clearance technique. No
      significant changes were found. In conclusion, the renal hemodynamic changes
      during ureteral obstruction are compatible with a predominant preglomerular
      vasoconstriction. The inter-relationship between obstruction, high pressure and
      reduction in RBF and GFR is substantiated. Moreover, variation in the reactive
      mechanisms between species with different kidney activities is established.

PMID- 8883037
TI  - Content of sulfur amino acids and vitamin B6 and related enzyme activities in
      rats with chronic renal failure fed a high methionine diet.
AB  - The effect of concentrations of sulfur-containing amino acids, activities of
      cystathionine gamma-lyase and cystathionine beta-synthase, and level of vitamin
      B6 were examined following menthionine administration in normal rats and
      chronically uremic rats with 7/8 nephrectomy. In the uremic rats, the serum
      levels of methionine, cystathionine, cysteine and taurine increased in proportion
      to the amounts of methionine administered. The increase of taurine content in the
      serum and liver was particularly marked. Cystathionine beta-synthase activity in
      the liver increased with the administration, but the serum level of pyridoxal
      phosphate decreased markedly. The body weight gain of rats decreased with the
      administration, and the contents of urea and creatinine in serum increased. Thus,
      vitamin B6 deficiency in chronically uremic rats administered with large amounts
      of methionine may reduce growth, lower renal function and cause abnormal
      metabolism of sulfur-containing amino acids.

PMID- 8883038
TI  - Amino acid profiles and muscle protein composition in rats with a reduced renal
      mass in the fed state.
AB  - In severe chronic renal failure (CRF) with associated metabolic acidosis,
      abnormalities in protein metabolism and amino acid (AA) profiles in the fed state
      are well described. To evaluate the effect of early uraemia and the influence of
      acid-base status on protein metabolism and AA profiles, three groups of pair-fed
      rats were studied: group I - rats with 1+ 1/2 nephrectomy; group II - rats with
      1+ 1/2 nephrectomy receiving NaHCO3 supplementation, and group III - sham
      operated rats with NaHCO3 supplementation. After 4 weeks, serum creatinine values
      were similar in groups I and II (111 +/- 5 and 119 +/- 4 mumol/l) and higher than
      in group III (51 +/- 5 mumol/l, p < 0.0001); HCO-3 was reduced only in group I
      (22.4 +/- 0.8 mmol/l) compared to group II (28.3 +/- 0.6 mmol/l, p < 0.001) and
      group III (28.2 +/- 1.3 mmol/l, p < 0.001). In the uraemic animals (groups I and
      II) arterial AA profiles showed increased levels of phenylalanine, glycine,
      glutamate, proline and alanine. The marked increase of threonine in group I was
      corrected by NaHCO3 supplementation in group II. The total nonessential AA were
      higher both in group I (1,832 +/- 53 mumol/l, p < 0.05) and group II (1,788 +/-
      103 mumol/l, p < 0.05) than in group III (1,542 +/- 54 mumol/l). These results
      are similar to those described in the fed state of uraemic patients.
      Intracellular AA changes were detected, especially in group II namely increased
      glycine and a decrease in threonine and serine levels. No signs of malnutrition
      or changes in alkali-soluble protein (ASP) or ASP/DNA ratio in liver and muscle
      were observed. These results show that AA abnormalities in the fed state occur
      early in the course of CRF, and that the marked increase of threonine is
      corrected by NaHCO3 supplementation. These data suggest that either an impaired
      utilization of the ingested proteins might occur before the appearance of major
      alterations in endogenous protein metabolism or acid-base status might alter AA
      metabolic rate per se.

PMID- 8883039
TI  - Transforming growth factor-beta in the development of rat diabetic nephropathy. A
      10-month study with insulin-treated rats.
AB  - We investigated the intrarenal distribution of transforming growth factor-beta 1
      (TGF-beta 1) protein and the TGF-beta 1 mRNA levels in the glomeruli and renal
      cortex of Wistar rats with streptozotocin-induced diabetes before and after the
      onset of diabetic nephropathy. Monthly urinary albumin excretion, glomerular
      filtration rate, glomerular volume, renal histology and immunohistochemical
      reaction for type-I collagen were also studied. The results showed progressively
      higher glomerular immunohistochemical TGF-beta 1 staining in rats with a diabetes
      duration of 24 and 40 weeks which was correlated with albuminuria (r = 0.905, p <
      0.01) and was temporally associated with the appearance of glomerular deposition
      of total and type-I collagen. The glomerular content of TGF-beta 1 mRNA was
      higher in rats diabetic for 20 weeks while lower cortical RNA-TGF-beta 1 levels
      were found in rats with a diabetes duration of 1-40 weeks. These data suggest
      that this polypeptide may be an important mediator of diabetic
      glomerulosclerosis.

PMID- 8883040
TI  - Morphine modulates mesangial immunoglobulin G uptake in rats with antithymocyte
      serum-induced mesangial cell injury.
AB  - The glomerular mesangium is an important site of activity in patients with heroin
      addiction. We studied the effect of morphine, a metabolite of heroin, on the
      mesangial immunoglobulin G aggregate uptake in a model of specific mesangial cell
      injury. Isolated specific mesangial cell injury was developed in Lewis rats by
      injecting intravenously antithymocyte serum (ATS). Forty-eight hours later,
      radioiodinated, heat aggregated immunoglobulin G (AHIgG125I) was administered (20
      mg/100 g i.v.) by tail vein. At 4 and 24 h, kidneys, liver, and spleen were
      removed, glomeruli isolated, and the radioactivity measured. Blood levels of
      AHIgG125I were measured at 0, 4 and 24 h. For ultrastructural studies, IgG-coated
      gold particles were injected, and the mesangial circulation was studied. At 4 h,
      ATS-treated rats showed a lower (p < 0.02) accumulation of AHIgG125I in the
      mesangium when compared with control rats (controls 511,012 +/- 10,807 vs. ATS
      464,614 +/- 7,944 cpm/g glomerular protein). ATS plus morphine treated rats
      showed a higher (p < 0.01) accumulation of of AHIgG125I when compared with rats
      treated with AS alone. Even at 24, h morphine-treated ATS rats showed a higher
      accumulation of AHIgG125I when compared with those treated with ATS alone.
      Ultrastructural studies showed aggregation of IgG-coated gold particles in the
      mesangial cell endolysosomes of control rats. Our results suggest that
      macromolecules may dwell longer in the mesangium of rats with intact mesangial
      cells. This increase in transit time may be related to the uptake of these
      macromolecules by mesangial cells. Morphine seems to enhance the accumulation of
      macromolecules in the mesangium, independent of its action on mesangial cells.

PMID- 8883041
TI  - Increased lipid peroxidation by rat liver microsomes in experimental renal
      failure.
AB  - This study investigated the peroxidative state of renal failure by measuring
      lipid peroxidation. The generation of lipid peroxides by rat hepatic microsomes
      was compared between experimental renal failure caused by 7/8 nephrectomy and
      healthy control animals. The concentrations of BUN at the point of sacrifice were
      84.2 +/- 18.4 (mean +/- SD) in nephrectomized and 19.8 +/- 4.3 mg/dl in the
      control group (p < 0.01, n = 5). Microsomal generation of thiobarbituric acid
      reactive substance was 31.2 +/- 2.8 in the nephrectomized group and 20.9 +/- 4.9
      nmol/incubation/min in the control group. There was a significant difference
      between the groups (p < 0.01, n = 5). In summary, the generation rate of lipid
      peroxides in the microsomes obtained from the rats with experimental renal
      failure was significantly higher than the control. This study confirms an
      increased peroxidative state, and specifies one of the sites of increased lipid
      peroxide generation in renal failure.

PMID- 8883042
TI  - Henoch-Schonlein purpura and membranoproliferative-like glomerulonephritis.
AB  - A 17-year-old man presented Henoch-Schonlein purpura with renal impairment,
      nephrotic syndrome needing transitory hemodialysis and hematuria. By light
      microscopy, the renal biopsy revealed membranoproliferative-like lesion
      associated with massive subendothelial deposits, some subepithelial deposits,
      hyalin thrombi and intracapillary neutrophils. By immunofluorescence, intense
      nodular and segmental deposits of IgG, IgM, IgA, C3, fibrinogen and C1q were
      found to be present in the intracapillary area and the mesangium. By electron
      microscopy, large subendothelial and rare subepithelial deposits were observed. A
      skin biopsy demonstrated leukocytoclastic skin vasculitis with IgA deposits in
      the arterial walls. Treatment with corticosteroids resulted in return renal to
      normal renal function but persistent proteinuria and hematuria. A second renal
      biopsy, performed after 2 months, showed a marked decrease in lesions and
      deposits. Fifteen months later, the patient presented normal serum creatinine
      level but proteinuria and hematuria persisted. At this time, a third renal biopsy
      was performed and showed segmental mesangial sclerosis and the decrease of
      disappearance of deposits. Two years after the first hospitalization, no abnormal
      serum creatinine or urinalysis were present. This report describes a detailed
      study of a case presented with Henoch-Schonlein purpura and morphologic features
      consistent with membranoproliferative-like lesion, who recovered normal renal
      function and urinalysis; repeat biopsies performed at intervals of 2 months and 1
      year confirmed the disappearance of mesangial proliferation, double contours and
      deposits.

PMID- 8883043
TI  - Steroid-responsive hypercalcaemic nephropathy in diabetes mellitus probably due
      to occult sarcoidosis.

PMID- 8883044
TI  - Transperitoneal removal of osteocalcin, calcitonin and parathyroid hormone in
      patients treated by CAPD.

PMID- 8883045
TI  - Nephrotic syndrome in two cases with sickle cell nephropathy.

PMID- 8883046
TI  - Beta 2-microglobulin as an indicator of interstitial cell infiltration in IgA
      nephropathy.

PMID- 8883047
TI  - 99mTc-DMS tubular fixation in Balkan endemic nephropathy patients.

PMID- 8883048
TI  - Guillain-Barre syndrome after renal transplantation: a case of clinical success
      with intravenous immunoglobulin therapy.

PMID- 8883049
TI  - Calculation of an 'adequate' Kt/V in the individual patient.

PMID- 8883050
TI  - Nephrotic syndrome accompanying hepatitis-B-related liver cirrhosis and delta
      hepatitis.

PMID- 8883051
TI  - Effect of beraprost sodium, a PGI2 analogue, on proliferation of cultured rat
      glomerular mesangial cells.

PMID- 8883052
TI  - Renal artery aneurysm manifested as parapelvic cyst on abdominal sonography.

PMID- 8883053
TI  - Hepatitis E seroprevalence in dialysis in southern Reunion Island.

PMID- 8883054
TI  - Acute oliguric renal failure in a patient with an Erysipelothrix rhusiopathiae
      bacteremia and endocarditis.

PMID- 8883055
TI  - Delayed decubitus perforation of the bowel is a sword of damocles in patients on
      peritoneal dialysis.

PMID- 8883056
TI  - Bleeding diathesis is uremic patients treated with peritoneal dialysis: role of
      platelet glycoproteins GPIb and GPIIb/IIIa abnormalities.

PMID- 8883057
TI  - The significance of renal tubular deposition of apolipoprotein A1.

PMID- 8883058
TI  - Ventricular tachycardia due to rapidly changing serum calcium levels following
      total parathyroidectomy.

PMID- 8883059
TI  - The reproducibility of cyclosporin-induced hemolytic uremic syndrome in a renal
      allograft recipient.

PMID- 8883060
TI  - Bioenergetic effects of erythropoietin in skeletal muscle.

PMID- 8883061
TI  - Heparin-associated thrombocytopenia during continuous venovenous hemofiltration.

PMID- 8883062
TI  - Significative improvement of renal function after correction of critical renal
      artery stenoses in patients with impaired renal function.

PMID- 8883063
TI  - The importance of delay in cannulation after hemodialysis vascular access
      surgery.

PMID- 8883064
TI  - Effectiveness of cysteamine and mesna in decreasing intracellular cystine content
      in cystinosis.

PMID- 8883066
TI  - Commentary: psychosocial concerns.

PMID- 8883065
TI  - Reader questions discussion of therapeutic touch.

PMID- 8883067
TI  - Commentary: malignant fibrous histiocytoma versus adenocarcinoma of the breast.

PMID- 8883068
TI  - Concerns, affect, and cognitive disruption following completion of radiation
      treatment for localized breast or prostate cancer.
AB  - PURPOSE/OBJECTIVES: To describe concerns, cognitive disruption, and affect
      following the completion of radiation treatment (RT) for localized breast or
      prostate cancer. DESIGN: Cross-sectional, descriptive. SETTING: Two RT centers
      associated with a university hospital. SAMPLE: Patients who completed RT for
      prostate (n = 9) or breast cancer (n = 11). The mean age of the sample is 64
      years. Ninety percent are Caucasian, 80% are married, 50% are of Latter-day Saint
      faith, and 50% are retired. All had early stage disease, with a mean of 20 months
      post-RT. METHODS: One-time interview using qualitative methods and the Life
      Orientation Test, Revised Impact of Events Scale, state scale of the Positive and
      Negative Affect Schedule, satisfaction items of the Sarason Social Support
      Questionnaire, and Side Effect Severity Checklist. MAIN RESEARCH VARIABLES:
      Frequency of intrusive thoughts or avoidant behavior, positive and negative
      affect, dispositional optimism, satisfaction with social support, severity of
      side effects, and themes extracted from semistructured interviews. FINDINGS: Most
      subjects had unexpected intrusive thoughts about cancer; more than one-third
      avoided reminders of cancer. The level of positive affect was high, as was
      optimism. The level of negative affect was low. Subjects' satisfaction level with
      social support was high. Fatigue was the most frequently reported continuing side
      effect. Relative optimism, acceptance, vigilance, and trust of healthcare
      providers were major themes. Avoidance, comparison, maintaining normalcy, and
      information seeking were common coping strategies. CONCLUSIONS: Subjects
      perceived themselves to be doing well. Fatigue was the most common long-term side
      effect. Subjects continued to seek information. Symptom vigilance and
      interpretation were important, as were having a positive outlook and maintaining
      normalcy. IMPLICATIONS FOR NURSING PRACTICE: Nurses must acknowledge the
      potential for concerns about symptoms and continuing side effects and what they
      mean for the patient. Clinicians need to provide accurate information about
      common post-treatment experiences. Clinicians also must remember that subjects
      have vivid recollections of both positive and negative interactions with
      healthcare providers.

PMID- 8883069
TI  - Testicular cancer: a review.
AB  - PURPOSE/OBJECTIVES: To describe the pathophysiologic mechanisms, histologic and
      clinical staging, diagnosis, and medical and nursing management of testicular
      cancer. DATA SOURCES: Published studies, review articles, and Physician Data
      Query database. DATA SYNTHESIS: Testicular cancer is a complex disease resulting
      from transformation of gonadal tissues. The pathophysiologic mechanisms involve
      damage to tissue in utero and after birth. Orchiectomy is the treatment of choice
      for early-stage disease. Orchiectomy can have profound physiologic and
      psychological consequences for young males. Subsequent chemotherapy and radiation
      therapy also may have severe side effects including azoospermia, bone marrow
      suppression, nephrotoxicity, and pulmonary toxicity. CONCLUSIONS: Early detection
      of this disease results in improved patient outcomes. Patients treated with
      radical inguinal orchiectomy and radiation therapy have fewer long-term side
      effects and toxicities than patients who require more extensive surgery and
      chemotherapy. IMPLICATIONS FOR NURSING PRACTICE: Nursing care must focus not only
      on relieving the patient's physical symptoms but on helping him deal with the
      psychosexual issues associated with the disease and its treatment.

PMID- 8883070
TI  - The quality of life of patients with cancer receiving hospice care.
AB  - PURPOSE/OBJECTIVES: To evaluate the outcomes of hospice services and explore
      factors that affect the quality of life (QOL) of patients with cancer receiving
      hospice care. DESIGN: Descriptive. SETTING: Two homecare hospices in the
      southeastern United States. SAMPLE: Convenience sample of 118 hospice patients
      with a diagnosis of cancer and their primary caregivers. METHODS: The Hospice
      Quality of Life Index (HQLI) was administered to patients and caregivers within
      48 hours of admission and after three weeks of hospice care. MAIN RESEARCH
      VARIABLE: QOL. FINDINGS: HQLI scores could range from a low of 25 to a high of
      250. Mean HQLI scores of the patients ranged from 168-173.7; the caregivers'
      means ranged from 157-158. Factor analysis confirmed four subscales:
      physical/functional, social/spiritual, psychological, and financial well-being.
      The social/spiritual subscale resulted in the highest mean scores (74.9), and the
      physical/functional subscale had the lowest (23.9). Correlations between patient
      and caregiver HQLI scores were only moderate (r = 0.51-0.55) CONCLUSIONS: Overall
      QOL remained stable during the study period when measured by an apparently valid
      and reliable instrument. QOL is characterized by multidimensionality and
      subjectivity. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to design
      interventions to support the QOL of people who are terminally ill, with a
      particular focus on the physical/functional aspects of care. QOL assessment data
      should be collected from patients whenever possible, and outcomes of care should
      continue to be studied using valid and reliable tools.

PMID- 8883071
TI  - Use of research-based practices by oncology staff nurses.
AB  - PURPOSE/OBJECTIVES: To determine the extent to which oncology staff nurses
      adopted eight specific research-based practices and the impact of demographic and
      resource factors on adoption of these practices. DESIGN: Cross-sectional mail
      survey. SETTING: National. SAMPLE: 1,100. METHODS: Network sampling techniques:
      2,000 Oncology Nursing Society (ONS) staff nurses were randomly and
      proportionally selected from seven practice setting categories; each ONS nurse
      was asked to recruit a non-ONS staff nurse colleague. Both groups completed the
      Oncology Nursing Practice Questionnaire, which measures adoption of eight
      research-based practices. MAIN RESEARCH VARIABLES: Extent of adoption, including
      awareness, persuasion, and implementation of eight specific practices; nurse
      demographics; and work-related resources. FINDINGS: Awareness was high, with 53%
      96% of nurses reporting awareness of the eight practices. Overall, 28% were aware
      of all practices while 10% were aware of half or fewer. Less-aware nurses
      differed from other nurses in demographics and resources. Computed "extent of
      adoption" scores showed that almost 90% of aware nurses used seven of the
      practices at least sometimes. CONCLUSIONS: Oncology staff nurses with awareness
      of a practice were implementing the practice in their organization. IMPLICATIONS
      FOR NURSING PRACTICE: The findings establish a need for developing educational
      programs to enhance awareness of specific practices and to creatively reach
      nurses who are unlikely to seek programs outside their employing agencies.

PMID- 8883072
TI  - Brain tumor support group: content themes and mechanisms of support.
AB  - PURPOSE: To describe the experiences and needs of patients with brain tumors as
      evidenced in analysis of themes from support group discussions and to increase
      knowledge of supportive mechanisms operant in support groups for medically
      vulnerable populations. DESIGN: Descriptive, exploratory. SETTING: An urban
      medical center on the U.S. West Coast. SAMPLE: Participants in a brain tumor
      support group, including patients, families, friends, and facilitators. METHODS:
      Researchers analyzed observational field notes and videotapes of a brain tumor
      support group's meetings over a six-month period using grounded theory methods to
      develop inclusive conceptual categories of themes and to document mechanisms of
      support. FINDINGS: Five thematic categories emerged: telling the story, managing
      medical advice, seeking and exchanging information, the long haul, and family
      life changes. Two major categories of supportive mechanisms emerged: finding a
      safe haven and maintaining morale, each of which contained several contributing
      dimensions. MAIN RESEARCH VARIABLES: Discussion topics, dialogue, and interaction
      among participants during the support group meetings. CONCLUSIONS: The support
      group provided a specific therapeutic forum for patients with brain tumors and
      their families, especially regarding the difficulties of survival and maintaining
      quality of life after initial treatment. IMPLICATIONS FOR NURSING PRACTICE:
      Findings generated knowledge that can guide patient care, particularly follow-up
      care after initial treatment. Support group facilitation by expert nurse
      clinicians can provide health-care guidance and emotional support to medically
      vulnerable patients and their families through symptom assessment and management,
      timely referral, therapeutic group process, promotion of self-care, and adaptive
      coping.

PMID- 8883073
TI  - Delayed complications of bone marrow transplantation: an update.
AB  - PURPOSE/OBJECTIVES: To review the delayed complications of bone marrow
      transplantation (BMT) with respect to specific problems, prognoses, causes, times
      of onset, and medical and nursing management. DATA SOURCES: Books, chapters,
      published professional articles, computerized data bases, and proceedings of
      national meetings. DATA SYNTHESIS: BMT, a life-saving measure for many patients
      with cancer, is associated with serious delayed complications. Morbidity and
      mortality from multisystem chronic graft-versus-host disease (GVHD), severe
      immunosuppression, sterility, growth and development problems, cataracts,
      relapse, secondary malignancies, and other complications can occur 100 days or
      more after BMT. Complications result from the effects of high-dose conditioning
      regimens, GVHD, transplant-related problems, and disease relapse. CONCLUSIONS:
      BMT is a life-saving measure associated with complications that can occur months
      to years after transplantation. Considerable research is needed to improve
      treatment for these complications and to increase the length of disease-free,
      long-term survival. IMPLICATIONS FOR NURSING PRACTICE: Nurses working with
      patients before and after BMT can be instrumental in managing long-term
      complications. Preparation of patients and families prior to, during, and after
      BMT can help alleviate anxieties throughout the continuum of recovery. Since the
      population of patients who have undergone BMT is growing, nurses in community and
      ambulatory settings need to include evaluation for physical and psychological
      sequelae of BMT as part of routine assessment, and symptom management as part of
      standard care.

PMID- 8883074
TI  - The oncology nursing image: lifting the mist.
AB  - PURPOSE/OBJECTIVES: To examine oncology nurses' perceptions of their professional
      image and describe implications and strategies for practice. DATA SOURCES:
      Individuals in 28 Oncology Nursing Society (ONS) image focus groups and 13
      validation focus groups in local ONS chapters throughout the United States. DATA
      SYNTHESIS: Although they used both negative and positive descriptors,
      participants believed the primary perceptions of physicians, administrators, and
      other nurses regarding oncology nurses were negative, whereas the perceptions of
      patients and families generally were more positive. Participants believed a lack
      of understanding exists about oncology nurses, their duties, and the impact of
      their specialized skills and knowledge on patient-care outcomes. They also
      believed that the current image of oncology nursing was not one they desired.
      CONCLUSIONS: Oncology nurses were concerned about their image and believed their
      external publics (e.g., physicians, administrators, nononcology nurses, patients,
      families) did not have a clear picture of who they are and what they do. They
      felt this lack of understanding led to diminished relationships with colleagues
      and patients/families and a lack of recognition of the oncology nurse as a valued
      member of the healthcare team. Participants felt this image could be changed and
      identified strategies to achieve their desired image through activities related
      to research, education, professionalism, communication, and influence.
      IMPLICATIONS FOR NURSING PRACTICE: Understanding the possible barriers to
      collaborative relationships, cost-effective care, disparate feelings of
      colleagues and external publics, and negative stereotypes will foster strategies
      to enhance relationships and improve care.

PMID- 8883075
TI  - Strategies to improve cancer education materials.
AB  - PURPOSE/OBJECTIVES: To highlight the benefits of creating effective materials for
      cancer education; to describe strategies to enhance the suitability of materials
      for all readers, including those with limited literacy skills. DATA SOURCES:
      Published research and education articles, health education models and theories,
      the National Cancer Institute Office of Cancer Communications, and personal
      experiences. DATA SYNTHESIS: Written materials, including visuals, commonly are
      used to convey cancer life-style risks, detection methods, treatments and
      procedures, and informed consent information. Such materials are relevant and
      suitable only when they can be read and understood and are matched to patients'
      reading abilities. A systematic process to achieve effective written materials
      includes assessing the target audience, limiting the educational objectives,
      focusing the content on the desired behaviors, presenting the context of the
      message first, and planning for reader interaction. The final step is
      verification of comprehension and suitability with the target audience.
      CONCLUSIONS: The creation of effective cancer education materials can be achieved
      by employing strategies that aim to enhance patient understandability, usability,
      relevancy, and motivation. Learner verification is a quality control process and
      a technique that helps ensure that materials are suitable for the intended
      audience and better matched to patients' learning needs. NURSING IMPLICATIONS:
      Nurses can improve the understandability of cancer education by using a variety
      of learning enhancement techniques and a set of organized planning steps. Such
      strategies can serve to improve the communication of cancer information to target
      groups with diverse literacy skills.

PMID- 8883076
TI  - A daily flowsheet for an outpatient bone marrow transplant treatment center.
AB  - PURPOSE/OBJECTIVES: To develop a flowsheet for an outpatient bone marrow
      transplant treatment center that would decrease the time required to complete
      documentation and facilitate verbal reports. DATA SOURCES: Oncology nursing
      standards of care, clinical experience, and published books and articles. DATA
      SYNTHESIS: A comprehensive daily flowsheet was developed to provide consistency
      in assessments and documentation of a complex outpatient population. CONCLUSIONS:
      The implementation of the new flowsheet decreased the amount of nursing time
      spent on written documentation and verbal reports. Patients' daily assessments
      are tracked more easily using this form. IMPLICATIONS FOR NURSING PRACTICE: Staff
      satisfaction can be increased by reducing the amount of time spent on patient
      documentation.

PMID- 8883077
TI  - Development of a comprehensive nursing/toxicity assessment form.
AB  - PURPOSE/OBJECTIVES: To develop and implement a form that integrates nursing and
      clinical trials toxicity assessments and interventions. DATA SOURCES: Published
      books, journal articles, and toxicity scales. DATA SYNTHESIS: The combined
      nursing and biometry department Documentation/Toxicity Committee at the London
      Regional Cancer Centre designed and implemented the comprehensive Patient
      Assessment Record (PAR) to provide consistent nursing and toxicity data related
      to patients enrolled in clinical trials research protocols. Nursing interventions
      and evaluations are documented on the Nursing Intervention Record (NIR).
      CONCLUSIONS: Initial evaluation suggested that the PAR has been an effective
      form. Audit results indicated that the form minimizes the number of individuals
      collecting the same data while maintaining the quality of toxicity data.
      IMPLICATIONS FOR NURSING PRACTICE: The collection of toxicity data for patients
      enrolled in clinical trials protocols has been incorporated into primary nurses'
      job descriptions. This additional responsibility has enhanced their role. Both
      the PAR and the NIR have assisted the multidisciplinary teams in meeting their
      documentation needs.

PMID- 8883078
TI  - Preparing patients for home infusion therapy requires educational assessment.

PMID- 8883079
TI  - Patients receiving chemotherapy at home require special considerations.

PMID- 8883080
TI  - Nurses can prepare to manage anaphylaxis in the home infusion patient.

PMID- 8883081
TI  - Mechanical phlebitis in PICCs requires distinct treatment.

PMID- 8883082
TI  - Physiological influence on ocular photometry. A review.
AB  - During the development of the ocular photometer (OPM) since 1983, we have
      considered several physical and physiological factors that could potentially
      influence the measurement and its results. Attention has been given to
      respiratory, circulatory, and intraocular pressure provocations, and numerous
      publications document the influences or lack thereof. Most recently, the authors
      conducted a simple reproducibility study with only 1 observer and 1 subject.
      Measurement of the same 2 retinal sites during a 3-week period yielded no
      statistically significant differences, even under relatively extreme temperature
      conditions. Thus, changes in readings with the OPM may be considered due to
      variations within the eye, such as cataract. Thus, increase in lens density may
      be directly and correctly expressed by dual-site measurement of retinal
      brightness, resulting in the contrast transfer ratio.

PMID- 8883083
TI  - Nuclear magnetic resonance studies of sugar metabolism in the human infant lens.
AB  - We investigated sugar metabolism in lenses isolated from infants with stage-5
      retinopathy of prematurity (ROP). The lenses were incubated in 13C-labeled
      glucose (35.5 mM) or galactose (30 mM) for 24 h at 37.5 degrees C. Six to 8
      lenses were pooled for each experiment. 13C-nuclear magnetic resonance
      spectroscopy was then performed on perchloric acid extracts of these lenses.
      Active aldose metabolism was indicated by the production of lactate. However,
      neither sorbitol nor dulcitol was detected. On the other hand, an experimental
      aldose reductase inhibitor, sorbinil, caused a decrease in the hexose
      monophosphate shunt activity suggesting an active polyol pathway. Both polyols
      therefore appeared to have been metabolized further. In addition, galactose
      metabolism was unique in that it not only involved a galactose-->glucose
      epimerization, but also a direct galactose-->ribose conversion, and a production
      of galactose-3-phosphate. Although it is possible that the ROP lenses have
      adapted to oxidative stress during the postnatal high-oxygen incubation for
      premature infants, we believe the observed sugar metabolism is representative of
      the developing human lens.

PMID- 8883084
TI  - Ferricyanide reductase activity in cataractous human lens.
AB  - We assayed ferricyanide reductase activity (one of NADH-dependent diaphorase
      activities) in the soluble and insoluble fractions of cataractous human lenses.
      Activity of this reductase in both the soluble and insoluble fractions tended to
      decrease in order of cortex > nucleus periphery > nucleus center, and it was
      suggested that a decrease of the reductase activity is closely correlated with
      lens protein aggregation, and to some extent associated with the development of
      nuclear sclerosis (coloration) and cortical cataract. Furthermore, insoluble
      fraction had very high specific activity per mg insoluble protein in cortex, and
      the activity decreased sharply with an increase in the level of insoluble
      protein. The reductase activity in the insoluble fraction may be also related to
      the metabolic activity of plasma membranes.

PMID- 8883085
TI  - Anticataract action of vitamin E: its estimation using an in vitro steroid
      cataract model.
AB  - The aim of this study was to estimate the anticataract action of vitamin E using
      an in vitro methylprednisolone (MP)-induced cataract model. The same severity of
      early cortical cataract was induced in lenses isolated from male Wistar rats aged
      6 weeks by incubation with MP (1.5 mg/ml) in TC-199 medium. The cataractous
      lenses showed slight increases in lipid peroxide (LPO) content and Na+/K+ ratio
      and slight decreases in reduced glutathione (GSH) content and glyceraldehyde-3
      phosphate dehydrogenase (GAP-DH), a sensitive index of oxidative stress, and
      Na+,K(+)-ATPase activities. When the cataractous lenses were further incubated in
      TC-199 medium with and without vitamin E (250 micrograms/ml) for 48 h, the
      progression of cataract was prevented in the vitamin E-treated lenses, but not in
      the vitamin E-untreated lenses. The vitamin E-untreated lenses showed a decrease
      in vitamin E content and an increase in water content in addition to further
      increases in LPO content and Na+/K+ ratio and further decreases in GSH content
      and GAP-DH and Na+,K(+)-ATPase activities. In contrast, the changes of these
      components and enzymes except for GSH were attenuated in the vitamin E-treated
      lenses. From these results, it can be estimated that vitamin E prevents in vitro
      cataractogenesis in rat lenses treated with MP by protecting the lenses against
      oxidative damage and loss of membrane function.

PMID- 8883086
TI  - Racemization of lens crystalline constituents in UV-induced cataract evaluated by
      chiral GC/MS spectroscopy.
AB  - The racemization of amino acids is hypothesized to cause cataract by disrupting
      the crystalline's tertiary structure, which, in turn, alters the optical
      characteristics of the lens. To better understand the role of these modifications
      in cataractogenesis, the changes in stereoisomer ratio of amino acids from lens
      crystalline by UV-B-induced cataract in animal models were studied using chiral
      separation gas chromatography-single quadrupole mass spectroscopy. The
      anticataract action of a compound, ([1-(phenylmethyl)-1H-indazol-3-yl]oxy)acetic
      acid lysinate, was also evaluated by this method.

PMID- 8883087
TI  - Measured changes in cataract over six months: sensitivity of the Nidek EAS-1000.
AB  - Lens opacities in 98 eyes from 63 consecutive outpatients with cataract were
      recorded by both retroillumination and Scheimpflug slit methods by one operator.
      This was repeated at 26 +/- 1 weeks. Image analysis used the EAS-1000 software.
      Cortical and posterior subcapsular (PSC) cataracts were measured in
      retroillumination images as density more than 14 cct units below background
      density. Linear densitometry of white scattered light along the optical axis was
      measured for slit images by both peak density and mean density ('area under the
      curve'). Retroillumination images showed no discernible change over 6 months (the
      regression coefficient being as for the intersession reliability). Half of the
      Scheimpflug slit images could not be analysed because overlying cortical changes
      masked the more posterior parts of the lens. The other 49 eyes showed a
      significant increase in nuclear white scatter after 6 months, with greater
      degrees of change occurring in those eyes with the greatest amount of nuclear
      cataract initially. This is reflected by the decreased intraclass correlation
      coefficient (R = 0.42). The area of lens showing greatest change was the anterior
      fetal nucleus. The Nidek EAS-1000 is able to detect changes over a 6-month period
      in nuclear density but not in cortical or PSC cataract. The rate of progression
      of nuclear white scatter increases as the lens opacity becomes more dense. The
      ability to detect change in cataract over 6 months has implications for
      epidemiological studies and for trials of anti-cataract drugs.

PMID- 8883088
TI  - Imaging spectrometry in ophthalmology--principle and applications in
      microcirculation and in investigation of pigments.
AB  - Imaging spectrometry is a new technique that permits simultaneous measurements of
      reflectance spectra at different locations along a line. Results are three
      dimensional images, whose coordinates are location, wavelength, and reflectance.
      A conventional fundus camera is adapted to a spectrograph and an intensified
      charge coupled device (CCD) matrix detector system. The spectral resolution of
      this spectrometer is lower than 2 nm within a spectral range between 395 and 710
      nm. The local resolution is lower than 23 microns along a line of 1.5 mm. From an
      imaging spectrum, the extinction spectrum of blood in vessels can be calculated.
      Also, in case of a noisy extinction spectrum of blood, its approximation by a
      model function results in calibration-free measurement of the oxygen saturation.
      Considering the radiation transport in single fundus layers, the local
      distribution of the concentration-thickness product of xanthophyll, melanin, and
      choroidal blood can be calculated.

PMID- 8883090
TI  - UV-b-induced cataract model in brown-Norway rat eyes combined with
      preadministration of buthionine sulfoximine.
AB  - In order to develop a more adequate ultraviolet (UV)-induced cataract model, a
      combination of l-buthionine sulfoximine (BSO) treatment was applied to
      experimental animals. A single administration of BSO 4 mmol/kg caused reduced
      glutathione concentration until experimental day 8. In the 0.067-J/cm2 UV-B
      irradiation experiment, the light-scattering intensity of the anterior lens
      cortex of the combination group was significantly higher than that of the other
      groups during the second week after irradiation commenced. After the fourth
      experimental week, however, there was no significant difference between the group
      treated by UV-B alone and the combination group. In the 0.2-J/cm2 UV-B
      irradiation experiment, anterior polar cataract was seen in the group receiving
      UV-B alone, as already reported, 6 weeks after starting UV irradiation.
      Meanwhile, in the combination group, shallow cortical opacity was seen at 26
      weeks after the start of experiment in the deeper lenticular layer which was
      separated from the anterior subcapsular opacity. This anterior shallow cortical
      opacity seemed to move towards the nuclear region during the time course of the
      experiment. The results of this experiment suggested that the BSO treatment
      accelerated cataractogenesis through additional UV-B irradiation. Although more
      experiments are needed, this model is useful in investigating the connection
      between UV-B and other cocataractogenic factors in age-related cataract in
      humans.

PMID- 8883089
TI  - Precataractous changes affect lens transparency in the selenite cataract.
AB  - Selenite treatment of the preweanling rat stabilized the transparency of the lens
      nucleus to decreasing temperature. Hence, we compared properties of the cortex
      and nucleus from lenses of selenite-treated and age-matched control rats. A
      subcutaneous dose of 30 nmol Na2SeO3/g body weight was administered to 10- to 13
      day-old Sprague-Dawley rats. Uninjected, age-matched littermates served as
      controls. As required, lenses were frozen in liquid N2 and separated into nuclear
      and cortical-epithelial fractions. Transparency of solutions of lens proteins (90
      100 mg per ml) was monitored from 30 to 2 degrees C as percent transmittance (%T)
      at 490 nm. The critical phase separation temperature, Tc, was the temperature at
      80%T. Protein associations were monitored with gel filtration chromatography. The
      nuclear 'cold cataract', in intact lenses, formed at similar temperatures at 14
      and 15 days of age, but at a significantly lower temperature when the lenses were
      from a selenite-treated rat. The Tc, however, was greater by 1.5-2 degrees C for
      solutions of proteins isolated from whole lenses or lens nuclei from rats 24 and
      48 h after treatment with selenite. Further, less gamma-crystallin was associated
      with the alpha-crystallin fraction in extracts from the nucleus of lenses from
      treated rats. Altered phase separation properties occurred as an early event in
      the etiology of selenite cataract. The different in vivo and in vitro responses
      to temperature indicated that properties of lens crystallins do not solely
      establish transparency in the intact lens.

PMID- 8883091
TI  - Inhibition of steroid-induced cataract in rat eyes by administration of vitamin-E
      ophthalmic solution.
AB  - The efficacy of a vitamin-E (VE) ophthalmic solution was evaluated on a newly
      developed rat steroid-induced cataract model. Brown Norway rats irradiated with 2
      Gy X-ray, right eyes only, were divided into 5 groups: the control group; 2
      steroid (1 mg/kg/day)-treated groups with topic (Top) and systemic (Sys)
      administration, and 2 VE-treated groups, 1 with the same treatment as the Top
      group with the addition of 5% VE twice a day (Top + VE) and 1 with the same
      treatment as the Sys group with 5% VE twice a day (SYS + VE). The lens changes
      were documented with a Scheimpflug camera and changes in light scattering were
      evaluated quantitatively. The VE-treated groups (Top + VE and Sys + VE) showed a
      significant inhibition of the increase in the opaque area compared with each of
      the non-VE-treated groups. The VE ophthalmic solution was strong enough to
      prevent steroid-induced cataract in rats.

PMID- 8883092
TI  - Evaluation of transparency and barrier function of the cornea by Scheimpflug
      images.
AB  - Two new methods of corneal analysis with Scheimpflug images will be introduced in
      this paper. The first study was to document the light scattering of the cornea
      itself using a newly modified Scheimpflug camera with higher magnification.
      Details of the slit images of the cornea could be evaluated more precisely than
      those of images taken with an existing camera. The second study was to evaluate
      the corneal epithelial barrier function by measuring the intensity of the light
      scattering originating from instilled fluorescein excited through filters.
      Fluorescein accumulation in the damaged epithelium and diffusion with time into
      the stromal tissue could be observed in two-dimensional images and the changes
      could also be documented by measuring the intensity and extent of light
      scattering. These newly developed methods will be useful for studies of the
      cornea.

PMID- 8883093
TI  - Calcium distribution in the human eye lens.
AB  - The distribution of calcium in the human eye lens was investigated using the
      oxalate-pyroantimonate technique. In epithelial cells and superficial cortical
      fibers calcium is sequestered and tightly bound to proteins in the endoplasmic
      reticulum, nuclear envelope, Golgi cisterns and mitochondria. In intermediate
      fibers these cell organelles are broken down and the liberated calcium is
      ionically bound to the phospholipids at the extracellular side of the fiber
      limiting membrane. It is argued that calcium is probably additionally bound to
      beta-crystallin. This site-specific variation in calcium storage might explain
      the deeper cortical localization of early focal dot opacities and retrodots.

PMID- 8883094
TI  - Imaging of the spatial density distribution on the capsule of the lens with
      Scheimpflug photography.
AB  - The density characteristics of the anterior and posterior surfaces of the lens,
      although of primary importance for its optical quality, are difficult to
      determine. Scheimpflug photography, however, allows distinct density measurements
      from the optical axis towards the periphery with the only limitation of a
      sufficient mydriasis, so that a 3-dimensional scatter profile of both capsular
      surfaces can be calculated via multilinear densitometric evaluation of a
      sufficient number of meridians. On this methodical basis, we analysed Scheimpflug
      images recorded with the Topcon SL-45 on Kodak T-Max 400 film from 25 patients in
      an age range between 19 and 63 years. Images from the 0 degree + 45 degree
      meridians were scanned with multilinear microdensitometry and the data computed
      to get a density profile. In general, most scattering profiles show a marked
      interindividual variability. Nevertheless, a general trend can be established
      between the periphery and the center of the anterior and posterior capsules: (a)
      the anterior capsule generally has a higher density than the posterior; (b) in
      most cases, the center of the posterior capsule has a higher density than the
      periphery; (c) the anterior capsule has a more uniform spatial density
      distribution in all cases. From the cases evaluated, it can be concluded that the
      density of the peripheral posterior capsule is more importantly influenced by
      shading effects of the iris, so that geometrical correction is needed.

PMID- 8883095
TI  - A new steroid-induced cataract model in the rat: long-term prednisolone
      applications with a minimum of X-irradiation.
AB  - In order to induce experimental steroid cataracts in rat eyes similar
      morphologically to those seen in human eyes, prednisolone acetate was
      administered either topically or systemically for 12 months with a low dose of X
      irradiation as a cocataractogenic factor. Twenty-seven Brown-Norway rats were
      randomly divided into a control group (group I) with no steroid administration;
      an eyedrop group (group II) with a daily 1% prednisolone acetate instillation of
      a total volume of 1.0 mg/kg in both eyes, and a systemic group (group III) with a
      daily intramuscular injection of 0.8-1.0 mg/kg prednisolone acetate. The right
      eyes of animals in each group were X-irradiated with a single dose of 2 Gy.
      Topical and systemic steroid administrations started 2 weeks after X-irradiation.
      Anterior segment changes were documented with a slitlamp microscope and an
      anterior eye segment analysis system once a month. Body weight and blood glucose
      levels were examined every week and every 2 weeks, respectively. The mortality
      rates in groups I, II and III were 0, 11 (1/9) and 25% (3/12), respectively. The
      both lenses in group I showed a gradual increase in light-scattering intensity in
      the nuclear and supranuclear regions over time. Initial lens changes in both
      steroid-treated groups were Y-suture dissociation and a slight increase in light
      scattering intensity in the posterior supranuclear region 3 months after
      prednisolone administration. Opacification of the anterior shallow cortex and the
      posterior subcapsular layer was observed after 10 months. X-irradiated eyes
      showed more prominent lens opacification as compared with nonirradiated eyes
      after 10 months in both group II and group III. Either topical or systemic
      administrations of prednisolone acetate over a long term successfully induced
      morphological lenticular changes in the rat similar to those found in human
      steroid-induced cataracts. A low dose of X-irradiation effectively accelerated
      opacification as a cocataractogenic risk. This new model will allow future
      investigation of steroid cataracts.

PMID- 8883096
TI  - Rotating slit image camera TOPCON SL 45. New developments for simultaneous image
      acquisition by photographic and CCD-assisted on-line documentation.
AB  - In a first approach the photographic camera part of the SL 45 B has been replaced
      by a CCD camera (2/3" black-and-white camera/Teli CS 3440 CCD B/W Tokyo
      Electronic Industry Co., Ltd.) unit thus enabling direct image acquisition and
      computer assisted analyses. Images have a full length of 8.8 mm. The images can
      be taken with only the observation light, no flash is necessary. Thus, the images
      can also be recorded on a VCR performing a complete rotation of the slit and all
      lens sections can be monitored obtaining almost three-dimensional information
      about the lens transparency/cataract formation. The further improvement is the on
      line imaging for all SL-45 cameras in having CCD acquisition together with the
      usual 35-mm film photography. This is very important for the documentation of the
      lens coloration and for measuring lens fluorescence. For this TOPCON SL 45 (new
      generation) we are using the '2nd Scheimpflug condition' located within the eye
      piece of a SL 45 which is taken with a CS b/w No. 8310 C (Tokyo Electronic
      Industry Co., Ltd.). It is possible to integrate the CCD system in all TOPCON SL
      45 Cameras (1st and 2nd production charge as well as SL 45 B).

PMID- 8883097
TI  - In vitro precipitation of rat lens crystallins by calpain I--a calpain requiring
      low amounts of calcium for activation.
AB  - The overall goal of this study was to provide data on the function and
      physiologic significance of lens calpain I, a cysteine protease requiring low
      amounts of calcium for activation. Reverse-transcriptase polymerase chain
      reaction was used to detect mRNAs for calpains I and II in young rat lenses. An
      in vitro model of crystallin precipitation was used to assess the ability of
      calpain I to induce hydrolysis and precipitation of crystallins. We found that
      incubation of crystallins with purified calpain I was indeed a powerful inducer
      of crystallin precipitation. However, mRNA levels for calpain I in whole lens
      appeared to be lower compared to calpain-II mRNA. Participation of calpain I in
      crystallin precipitation during normal maturation of rodent lenses or cataract
      formation is thus theoretically possible, but unlikely, because of the low level
      of expression of calpain I.

PMID- 8883098
TI  - Three-dimensional confocal microscopy of the lens.
AB  - A confocal microscopic technique is described to obtain optical sections from the
      in situ ocular lens of the rabbit and mouse. Optical sections were obtained with
      blue light through the full thickness of the lens epithelium, and of the anterior
      lenticular fibers. An image showing the structure of an anterior suture was
      obtained from the murine lens. A three-dimensional volume visualization of
      lenticular fibers from the anterior region of the rabbit lens was reconstructed
      from a stack of optical sections. These in situ microscopic observations of
      unstained, unfixed specimens correspond to previous studies using electron
      microscopy.

PMID- 8883099
TI  - Three-dimensional volume visualization of the in vivo human ocular lens showing
      localization of the cataract.
AB  - An in vivo human lens containing a cataract has been visualized by volume
      rendering a transformed series of 60 rotated Scheimpflug digital images. The data
      set was obtained by rotating the Scheimpflug camera about the optic axis of the
      lens in 3-degree increments. The set of 60 Scheimpflug digital images were
      mathematically transformed into a new data set in which the images are oriented
      perpendicular to the optic axis of the eye. The transformed set of optical
      sections were first aligned to correct for eye movements during the data
      collection process, then rendered into a three-dimensional volume reconstruction
      with volume-rendering computer graphics techniques. The viewpoint and the
      transparency of the volume rendered in vivo human lens were varied in order to
      observe volume opacities in various regions of the lens. To help visualize lens
      opacities, the intensity of light scattering was pseudocolor-coded as an integral
      part of the three-dimensional volume rendering. Three-dimensional, pseudocolored
      volume rendering of the in vivo human ocular lens represents a new technique to
      visualize in vivo human cataracts.

PMID- 8883100
TI  - Laser Scheimpflug videography.
AB  - Conventional Scheimpflug photography uses slits with a constant width of 80
      microns. This parameter limits the resolution as sharp contours are imaged with a
      basic uncertainty. In order to reduce this basic uncertainty we developed an
      illumination slit with a width of 20 microns and less, using a green helium-neon
      laser (543 nm). With this slit, much sharper imaging of ocular contours can be
      achieved. Since this illumination is coupled to on-line videographic detection of
      the Scheimpflug image, any adjustment of the target is done under visual control
      at the monitor. Using this device, the slope of a densitogram of contrasted
      contours (for example the corneal surfaces) is steeper, which guarantees a more
      accurate detection of corneal thickness and curvature.

PMID- 8883101
TI  - Molecular masses of gamma-crystallins.
AB  - Bovine gamma-crystallins were isolated and analysed by electrospray mass
      spectrometry (ESMS). The mass of gamma II-crystallin was as predicted from the
      amino acid sequence and the mass of gamma IIIb-crystallin was close, but the mass
      of gamma IVa-crystallin was 59 Da greater than that expected. gamma IVa
      Crystallin was digested with cyanogen bromide and the fragments were isolated
      before analysis by ESMS. The masses of the fragments did not correspond to the
      published sequence. The published sequence of gamma IVa-crystallin, which has
      been used to predict its three-dimensional structure, is incorrect.

PMID- 8883102
TI  - Distributional change of alpha-tocopherol in the rat lens with age.
AB  - Concentration of alpha-tocopherol (alpha-Toc.) in the rat lens (1, 4 and 12
      months old) was determined in single lenticular layers using gas chromatography
      and mass spectrometry. The highest concentration of alpha-Toc. in lens was found
      in the nucleus, followed by the deeper anterior and deeper posterior cortices,
      the shallow anterior and shallow posterior cortices, and the equatorial region.
      The topographic alpha-Toc. distribution in the lens did not differ between lenses
      of 1-, 4- and 12-month-old rats. A significant decrease of alpha-Toc.
      concentration was seen in lenses of 4- and 12-month-old rats compared to those 1
      month old. Concentration and distribution in 4- and 12-month-old rat lenses were
      almost the same. The concentration of alpha-Toc. in the lens changes in relation
      to age.

PMID- 8883103
TI  - Molecular mechanisms of olfactory processing in the mammalian olfactory
      epithelium.
AB  - In humans the sense of smell plays an important role in protecting the organism
      from external hazards like fire, gas or spoiled food, in the consumption of food
      and in chemical communication with one another. Increasingly, the study of human
      olfaction is relevant to a number of medical problems connected with olfactory
      dysfunction, i.e. neurodegenerative diseases which are also manifested in the
      olfactory epithelium. Although much is known about behavioral aspects and
      neuronal activities elicited by odorants, we still cannot clearly describe the
      molecular mechanisms by which odor stimuli are transformed into an electrical
      cell signal. Here recent progress in our knowledge about the molecular elements
      of the transduction machinery are reviewed. It can help to understand the general
      principles underlying our sense of smell.

PMID- 8883104
TI  - Focal metabolic activation in the predominant left auditory cortex in patients
      suffering from tinnitus: a PET study with [18F]deoxyglucose.
AB  - Eleven patients suffering from chronic disabling tinnitus underwent an FDG-PET
      study (positron emission tomography with [18F]deoxyglucose). Nine tinnitus
      patients revealed a significantly increased metabolic activity in the left, 1 in
      the right primary auditory cortex (PAC, Brodmann area 41). These results were
      statistically significant when compared to 14 healthy control individuals without
      tinnitus. A negative result was obtained from a chronic tinnitus patient but who
      had no subjective complaints during the period of PET investigation. One patient
      was first investigated during a disabling tinnitus period, later during a period
      with tinnitus relief and again when suffering from severe tinnitus. The metabolic
      activity of his left PAC was in good accordance with the subjective degree of
      tinnitus complaints present during each PET investigation. Although for the first
      time these results give objective evidence of tinnitus sensation and
      localization, they are difficult to interpret because of the limited research
      data available that combine functional brain imaging and acoustic stimuli.

PMID- 8883105
TI  - Computed tomographic image analysis of ears with otosclerosis.
AB  - To evaluate the usefulness of quantitative analysis of computed tomographic
      images in diagnosing stapedial otosclerosis, high-resolution temporal bone
      computed tomography (CT) of 32 ears with otosclerosis and 19 control ears was
      used. The images on the section containing the oval window were digitized using a
      scanner, and the ratio of the mean gray scale value of 5 areas in the optic
      capsule including the area anterior to the oval window to that of the cortical
      bone was calculated. The mean value of the ratio of the area anterior to the oval
      window was significantly lower in the otosclerosis group (0.85 +/- 0.10) than in
      the control group (1.03 +/- 0.03; Student t test: t = 7.94, p < 0.0001). In 30 of
      32 (93.7%) otosclerotic ears, the values were lower than the normal range
      calculated in the control group. This method of quantitative CT image analysis
      comparing the area anterior to the oval window was considered useful in
      diagnosing stapedial otosclerosis.

PMID- 8883106
TI  - Comparison of horizontal nystagmus in different head positions: a study by damped
      pendular rotation test.
AB  - Damped pendular rotation was given with the initial maximum speed of 180
      degrees/s. The subject's head was tilted forward at an angle of 30 degrees from
      the upright position, or kept in the upright position, or tilted backward at 30
      degrees from the upright position. Electronystagmography was used to evaluate the
      maximal slow-phase eye velocity (mx SPEV) of the horizontal nystagmus.
      Differences existed in mx SPEVs of the horizontal nystagmus for the head-tilted
      positions at 30 degrees forward or backward and that obtained in the upright
      position. The mx SPEV of the horizontal nystagmus in the upright position was
      higher than those acquired in the head-tilted positions.

PMID- 8883107
TI  - The vestibular nerve: its course to the anterior and lateral ampullae.
AB  - The course of the ampullary nerve to the anterior and lateral ampullae was
      studied using 25 human temporal bones. Sudan Black B staining was applied to
      decalcified temporal bones in order to stain nerve fibers. After removing the
      external and middle ear, each temporal bone was divided into four blocks by three
      parallel planes, making an angle of 45 degrees to the long axis of the stapes
      footplate or a line along the stapedial tendon. Two planes were in contact with
      the anterior and posterior margin of the oval window, respectively. The third
      plane passed through the capitulum of the stapes. Distances from the upper margin
      of the oval window, to the distal and proximal part of the ampullary nerve, to
      the facial nerve, and to the utricular macula were measured in the third plane.
      The thickness of the thinnest part of the wall of the facial canal facing the
      stapes was also measured. A new surgical approach to the ampullary nerve is
      discussed.

PMID- 8883108
TI  - Morphometric and ultrastructural findings on human vestibular ganglion cells.
AB  - Eight human temporal bones (4 patients) were fixed within 2 h after death by
      perilymphatic perfusion through the oval and round windows. After preparation, 30
      micron-thick sections were cut for light microscopy and ultrathin sections for
      ultrastructural evaluation. Under the light microscope, the diameter, the
      circumference and the area of the vestibular ganglion cells were measured. The
      data were statistically analyzed. The histograms of cell measurements showed two
      maxima. When observing the diameter of cells, one was at 40 microns and the other
      at 28 microns. Under the light microscope, we could distinguish two cell types,
      which mainly differed in size and content of granules in the cytoplasm.
      Ultrastructurally we identified also two cell types: larger cells with many
      mitochondria, dark clusters of endoplasmic reticulum and a varying amount of dark
      stained lysosomes in the cytoplasm and smaller cells with only few mitochondria,
      no lysosomes and an extended rough endoplasmic reticulum. None of the
      ultrastructurally analyzed ganglion cells were myelinated.

PMID- 8883110
TI  - Usefulness of auditory brainstem responses at high stimulus rates in the
      diagnosis of acoustic neuroma.
AB  - The effects of the stimulus rate on the auditory brainstem responses (ABRs) of
      acoustic neuroma (AN) patients were studied. Ninety-decibel click stimuli at a
      normal hearing level were delivered at stimulus rates of 9.5, 20, 40 and 90 Hz,
      and ABRs were recorded of 40 AN patients (40 ears) at each stimulus rate.
      Subjects with normal hearing (42 ears) and patients with sensorineural hearing
      loss (30 ears) were also studied to obtain normative data. The following two
      parameters were examined: the interpeak latency difference between wave I and
      wave V (IPL I-V) at each stimulus rate, and the increase in IPL I-V (delta IPL I
      V) when the stimulus rate was increased from 9.5 Hz. AN patients showed
      significantly larger values for both parameters at all stimulus rates compared to
      those of the control groups. Among 6 AN patients with normal ABRs at 9.5 Hz, 5
      showed abnormal IPL I-V or abnormal delta IPL I-V at 90 Hz, when the upper normal
      limits of both parameters were defined as the mean plus 2 SD of the group with
      normal hearing. These results suggest that recording ABR at high stimulus rates
      provides valuable information for detecting AN patients with normal ABRs.

PMID- 8883109
TI  - Effect of organophosphorus compound intoxication on auditory brainstem response
      in mini pigs.
AB  - Organophosphorus compounds (OPC) are widely used as insecticides and cause a high
      number of acute and chronic intoxications in man. Their toxicological properties
      lead among others to disturbances of the central nervous system. Hearing
      disturbances have been reported after chronic exposure to OPC, and changes in
      bioelectric brain activity have been observed during the acute state of
      intoxication. The EEG showed no characteristic alterations. We performed a
      threshold auditory brainstem response (ABR) in 12 mini pigs before, during and
      after paraoxon (a typical OPC) intoxication with a high dose of 27 mg/kg BW.
      During the application of paraoxon we saw a prolongation of the interpeak
      latencies Jewett I-V of approximately 1 ms. A threshold shift of 10-20 dB was
      seen in 8 animals. After the application, while the systemic effect of the
      paraoxon intoxication was still apparent, the threshold shift disappeared except
      for 2 animals and the prolongation of the interpeak latencies could not be
      observed any more. No characteristic signs of paraoxon intoxication could be seen
      in the ABR after the application was completed. Acute intoxication with an OPC
      only leads to temporary, limited hearing impairment and increased interpeak
      latency. We could not observe characteristic changes in the ABR corresponding to
      the state of intoxication.

PMID- 8883111
TI  - Expression of vasoactive intestinal peptide, substance P and bombesin-flanking
      peptide in nasal polyps.
AB  - The presence of neuropeptide-containing sensory, parasympathetic and sympathetic
      nerves in human nasal mucosa is well established. However, information regarding
      the neuropeptide distribution in nasal polyps is still lacking. The aim of this
      study was to compare immunohistologically the presence and distribution of
      substance P (SP), vasoactive intestinal peptide (VIP) and bombesin-flanking
      peptide (BFP) in normal nasal mucosa and nasal polyps. The expression was studied
      using Formalin-fixed and paraffin-embedded biopsy sections from 20 patients with
      nasal polyps and 10 controls with normal nasal mucosa from the anterior part of
      the inferior turbinate. Indirect immunohistochemistry (APAAP method) with mono-
      and polyclonal antibodies was used. None of the control group but 5 patients of
      the nasal polyp group had an atopic disease. Comparing localization and intensity
      of the immunohistological reaction in nasal mucosa and nasal polyp tissue, there
      was no difference in the expression of the three neuroendocrine substances. There
      was no difference of expression in the polyposis group itself concerning allergic
      and nonallergic subjects. The results indicate that VIP, SP and BFP have an equal
      distribution in nasal polyps and normal nasal mucosa.

PMID- 8883112
TI  - Clinical study of the role of melanocytes in the inner ear of patients with
      Harada's disease.
AB  - Harada's disease is an autoimmune disorder involving melanocytes. Twenty patients
      with Harada's disease underwent otoneurological examination to investigate the
      inner ear involvement in Harada's disease and the function of the melanocytes in
      the inner ear. All 20 exhibited clinical and/or laboratory abnormal inner ear
      findings. The incidence of inner ear involvement in Harada's disease is very
      high. The melanocytes in the inner ear play important roles in both auditory and
      equilibrium function.

PMID- 8883113
TI  - Papillary carcinoma of the thyroid originating in a thyroglossal cyst. Report of
      a case and diagnostic criteria.
AB  - A 34-year-old female with papillary carcinoma of the thyroid originating in a
      thyroglossal cyst is described. The patient's chief complaint was a submental
      mass. The mass was 6 x 4 cm, elastic, soft, and smooth-surfaced. CT examination
      showed high-density areas in part of the interior of the mass. Resection of the
      mass was attempted with a diagnosis of thyroglossal cyst. Since papillary
      carcinoma of the thyroid was noted in the cyst by intraoperative frozen section
      pathological examination, primary carcinoma of the thyroid was suspected, and the
      thyroid and surrounding areas were examined. Since no abnormalities were noted in
      the thyroid, the thyroid was preserved. According to the following reasons, the
      tumor was considered to be primary papillary carcinoma of the thyroid arising in
      the thyroglossal cyst: (1) Scar formation was noted in the center of the tumor;
      (2) tumor cells partly infiltrated into the surrounding tissues, and (3) no tumor
      was noted in the thyroid. A definitive diagnosis of carcinoma arising in the
      thyroglossal cyst has required confirmation of the absence of carcinoma in the
      thyroid by total thyroidectomy. In the present case, however, total thyroidectomy
      was avoided, because no gross pathological changes were observed in the thyroid
      during the operation. This decision may be controversial both diagnostically and
      therapeutically, but we consider from our observation of the course that total
      thyroidectomy is not always necessary.

PMID- 8883114
TI  - Prevention of osteoporosis: cost-effectiveness of different pharmaceutical
      treatments.
AB  - The cost-effectiveness of different pharmaceutical programmes to prevent
      osteoporosis has been compared. The following pharmaceutical treatments were
      analysed and compared: calcium supplementation, etidronate and calcitonin. As a
      benchmark for comparison, oestrogen replacement therapy, in the form of both
      pills and plaster, was also included in the analysis. The cost-effectiveness of
      different strategies for particular age groups was analysed. Finally, the cost
      effectiveness of population-based prevention programmes was compared with the
      cost-effectiveness of programmes based on screening followed by treatment of
      women with low bone mineral density (BMD). A cost-effectiveness analysis (CEA)
      was carried out. The cost/effectiveness ratio computed was net costs per hip
      fracture avoided. The evaluation was based on a simulation model in which 1000
      women were followed from the age of 50 years. The model was based on Danish
      epidemiological data and Danish health care cost figures. Assumptions concerning
      the health effect of the pharmaceutical methods of prevention were based on
      results from existing studies. As different results have been reported,
      'optimistic' and 'pessimistic' alternatives were simulated in the model. The
      analysis revealed large differences in the cost-effectiveness of different
      pharmaceutical methods; however, the cost-effectiveness is highly sensitive to
      the treatment effect assumed. Treatment will be more cost-effective the higher
      the fracture risk of the group treated, so cost-effectiveness will therefore
      increase the later in life the intervention takes place, and if only women
      screened for low BMD are treated. However, the overall effect from a general
      screening programme will be low and highly sensitive to compliance. As compliance
      with pharmaceutical treatment seems to be low, and as the effectiveness--and
      thereby the cost-effectiveness--is encumbered with much uncertainty, prevention
      of osteoporosis through screening for low BMD should not be recommended at
      present.

PMID- 8883115
TI  - The effect of calcium supplementation and Tanner stage on bone density, content
      and area in teenage women.
AB  - One hundred and twelve Caucasian girls, 11.9 +/- 0.5 years of age at entry, were
      randomized into a 24-month, double-masked, placebo-controlled trial to determine
      the effect of calcium supplementation on bone mineral content, bone area and bone
      density. Supplementation was 500 mg calcium as calcium citrate malate (CCM) per
      day. Controls received placebo pills, and compliance of both groups averaged 72%.
      Bone mineral content, bone mineral area and bone mineral density of the lumbar
      spine and total body were measured by dual energy X-ray absorptiometry (DXA).
      Calcium intake from dietary sources averaged 983 mg/day for the entire study
      group. The supplemented group received, on average, an additional 360 mg
      calcium/day from CCM. At baseline and after 24 months, the two groups did not
      differ with respect to anthropometric measurements, urinary reproductive hormone
      levels or any measurement of pubertal progression. The supplemented group had
      greater increases of total body bone measures: content 39.9% versus 35.7% (p =
      0.01), area 24.2% versus 22.5% (p = 0.15) and density 12.2% versus 10.1% (p =
      0.005). Region-of-interest analyses showed that the supplemented group had
      greater gains compared with the control group for bone mineral density, content
      and area. In particular, in the lumbar spine and pelvis, the gains made by the
      supplemented group were 12%-24% greater than the increases made by the control
      group. Bone acquisition rates in the two study groups were further compared by
      subdividing the groups into those with below- or above-median values for Tanner
      score and dietary calcium intake. In subjects with below-median Tanner scores,
      bone acquisition was not affected by calcium supplementation or dietary calcium
      level. However, the calcium supplemented subjects with above-median Tanner had
      higher bone acquisition rates than the placebo group with above-median Tanner
      scores. Relative to the placebo group, the supplemented group had increased
      yearly gains of bone content, area and density which represented about 1.5% of
      adult female values. Such increases, if held to adult skeletal maturity, could
      provide protection against future risk of osteoporotic fractures.

PMID- 8883116
TI  - A comparison of the effects of alfacalcidol treatment and vitamin D2
      supplementation on calcium absorption in elderly women with vertebral fractures.
AB  - Although vitamin D supplementation in the frail elderly improves calcium
      absorption, suppresses parathyroid hormone, decreases bone loss and reduces the
      risk of fractures, such treatment may be ineffective in patients with vertebral
      osteoporosis, because of impaired vitamin D metabolism or resistance to the
      action of vitamin D metabolites on the bowel. We have therefore performed a
      randomized, single masked study comparing the effects of alfacalcidol treatment
      (0.25 micrograms twice daily) and vitamin D2 supplementation (500-1000 units
      daily) on calcium absorption and bone turnover in 46 elderly women (median age 69
      years, range 64-79 years) with radiological evidence of vertebral fractures.
      Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of
      treatment with vitamin D2 (p < 0.001), but was unchanged in the group receiving
      alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in
      either group over the study period. Fractional 45Ca absorption increased after 3
      months of treatment with alfacalcidol (p < 0.05), but was unchanged with vitamin
      D2. There was also a reduction in plasma intact parathyroid hormone and serum
      alkaline phosphatase after 6 months of treatment with alfacalcidol (p < 0.05)
      which was not seen in the group receiving vitamin D2. Our study shows that
      vitamin D2 supplementation is ineffective in stimulating calcium absorption in
      elderly women with vertebral osteoporosis. By increasing calcium absorption in
      such patients, alfacalcidol may prove more effective than vitamin D in the
      management of vertebral osteoporosis.

PMID- 8883117
TI  - Ultrasound velocity and broadband attenuation over a wide range of bone mineral
      density.
AB  - Ultrasound velocity (UV) and broadband ultrasound attenuation (BUA) were studied
      in human and bovine bone with a wide range of bone mineral density (BMD). The BMD
      of 98 fresh specimens was measured by quantitative computed tomography: 42
      cancellous specimens from women in the age group of 64 +/- 4 years; 51 bovine
      cancellous and 5 bovine cortical. BMD values ranged from 90 to 400 mg/cm3 for the
      human cancellous bone, 310 to 870 mg/cm3 for the bovine cancellous bone, and 1750
      to 1780 mg/cm3 for the bovine cortical bone. BMD showed a strong linear
      correlation with apparent density over the entire range of density (r = 0.979).
      UV of human and bovine cancellous bone was 1480-2650 m/s and 2880-3100 m/s for
      bovine cortical bone. BUA values were 1-61 dB/MHz/cm for the cancellous specimens
      and 5-12 dB/MHz/cm for cortical specimens. UV was found to be linear with BMD for
      all specimens; however, BUA was linear with BMD only for the specimens from
      elderly women. A quadratic relationship between BUA and BMD was found when the
      bovine samples were included.

PMID- 8883118
TI  - New biochemical markers of bone resorption derived from collagen breakdown in the
      study of postmenopausal osteoporosis.
AB  - The aim of this work was to perform a comparative study between three recently
      developed biochemical markers of bone resorption derived from collagen metabolism
      -(1) total urinary free pyridinolines (Pyr), (2) serum pyridinoline cross-linked
      carboxy-terminal telopeptides of type I collagen (ICTP) and (3) a urinary
      specific sequence for a part of the C-telopeptide of the alpha 1 chain of type I
      collagen (CTX)--in the diagnosis and follow-up of postmenopausal osteoporosis.
      Results were also evaluated relative to the classical biochemical marker urinary
      hydroxyproline (Hyp). The study included 20 untreated osteoporotic postmenopausal
      women (OSP), age 60 +/- 6 years, range 46-69 years; 27 osteoporotic
      postmenopausal women treated (OSP-T) by cyclic therapy with disodium etidronate,
      25-hydroxyvitamin D and calcium for a period between 3 months and 4 years (25 +/-
      15 months), age 59 +/- 7 years, range 41-67 years; 17 osteopenic postmenopausal
      women, age 57 +/- 6 years, range 46 +/- 68 years; and 29 healthy control
      postmenopausal women, age 56 +/- 7 years, range 41-70 years. The diagnostic
      criterion for postmenopausal osteoporosis was a bone mineral density (BMD)
      (Hologic QDR-1000) in lumbar spine and/or femoral neck more than 2 SD below the
      mean value corresponding to an age- and sex-matched healthy control group. For
      inclusion in the osteopenic group BMD values had to be between 1 and 2 SD below
      the mean BMD value corresponding to the control group. We found a significant
      increase (p < 0.01) in the levels of Pyr/Cr and CTX/Cr (Cr = creatinine) in OSP
      patients with respect to the control group and we did not observe any significant
      difference between control and OSP-T or osteopenic women. It is interesting to
      note that there was a mean increase in CTX/Cr in OSP patients of 101% of the
      control values, while the mean increase found in Pyr/Cr concentration was only
      33%. However, we did not find significant differences in the concentrations of
      ICTP and Hyp/Cr between groups. In a comparison of Pyr/Cr and CTX/Cr, urinary CTX
      showed the higher diagnostic accuracy, as can be deduced from the receiver
      operating characteristic (ROC) curves. CTX sensitivity was 40% with a specificity
      of 100%, whereas the sensitivity was 25% for urinary Pyr/Cr. In conclusion, the
      results of the present work suggest that in osteoporotic women CTX has the
      highest diagnostic accuracy among the markers of bone resporption studied.

PMID- 8883119
TI  - Ultrasound parameters in osteoporotic patients treated with salmon calcitonin: a
      longitudinal study.
AB  - Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of ultrasound
      (US) in bone have been proposed as alternatives to radiation-based methods for
      the quantitative assessment of osteoporosis. However, the usefulness of US in
      monitoring response to treatment in osteoporotic patients has yet to be defined.
      To compare US with bone mineral density (BMD), we studied 112 osteoporotic women
      (age range 50-64 years). Seventy-eight of them were treated with salmon
      calcitonin nasal spray (CT; 200 IU/day, 1 month on and 1 month off) and calcium
      (500 mg/day); 34 patients were given only calcium. One hundred and four women
      complied with treatment throughout the 2-year study period. At baseline and after
      1 and 2 years we measured BMD at lumbar spine by dual-energy X-ray absorptiometry
      (DXA), and SOS, BUA and Stiffness index, by an Achilles ultrasound unit.
      Moreover, biochemical markers of bone turnover (alkaline phosphatase, osteocalcin
      and hydroxyproline) were also measured at baseline and after 6, 12 and 24 months.
      In the calcitonin-treated group at the end of the study period BMD had increased
      by 1.99%, SOS by 0.20%, BUA by 0.88% and Stiffness by 2.12%. By contrast in the
      calcium-treated group all parameters had decreased (BMD, -2.66%; SOS, -0.55%;
      BUA, -3.30%; Stiffness, -6.0%) by the end of the study period. The differences
      between groups were significant for BMD, SOS and Stiffness. At baseline a
      significant, but weak correlation was found between BMD and US parameters. The
      correlation coefficients between percentage changes at the end of the study
      period, in BMD and in SOS, BUA and Stiffness, were all significant (p < 0.001),
      being 0.41, 0.53 and 0.57 respectively. In conclusion, ultrasound measurements
      carried out in conjunction with BMD measurements will yield a more comprehensive
      assessment of skeletal status and may be helpful in monitoring the response to
      treatment in osteoporotic patients.

PMID- 8883121
TI  - The effect of a short course of calcium and vitamin D on bone turnover in older
      women.
AB  - Calcium and vitamin D (1200 mg/day + 800 IU) has been shown to reduce hip
      fracture incidence in older women living in long-term care facilities who had
      borderline low vitamin D levels. We examined the effect of a short course of
      calcium and vitamin D on biochemical markers of bone turnover in older community
      living women. Twelve community-living women (mean age 75 years) in good general
      health, without diseases or on medications known to affect bone, were entered
      into the study. All women were treated with calcium citrate (1500 mg/day of
      elemental calcium) and vitamin D3 (1000 IU/day) (Ca + D) for 6 weeks. Biochemical
      markers of bone turnover were measured in serum and urine collected at baseline
      (two samples), 5 and 6 weeks on Ca + D, and 5 and 6 weeks after termination of Ca
      + D. Markers of bone formation were osteocalcin, bone alkaline phosphatase and
      type I procollagen peptide. Markers of bone resorption were urinary
      hydroxyproline, free pyridinoline and deoxypyridinoline crosslinks, and N
      telopeptides of type I collagen. Parathyroid hormone (PTH) and 25-hydroxyvitamin
      D were also measured at baseline, 6 weeks on treatment and 6 weeks after
      termination of treatment. All markers of bone resorption decreased on Ca + D and
      returned to baseline after termination of Ca + D (p < 0.05). Markers of bone
      formation did not change with Ca + D treatment. PTH decreased on Ca + D and
      returned to baseline after treatment, and 25-hydroxyvitamin D increased with
      treatment and remained elevated 6 weeks after the end of treatment. We conclude
      that Ca + D reduces bone resorption in older women, possibly by suppressing PTH
      levels.

PMID- 8883120
TI  - Comparison of bone densitometry of the phalanges, distal forearm and axial
      skeleton in early postmenopausal women participating in the EPIC Study.
AB  - We present baseline bone densitometry from the Early Postmenopausal
      Interventional Cohort study (EPIC, sponsored by Merck, Sharp & Dohme) for the
      first time, in which 1609 women from England, Oregon, Hawaii and Denmark are
      participating to investigate the efficacy of daily oral alendronate to prevent
      early postmenopausal bone loss. We compared radiographic absorptiometry (RA) of
      the phalanges for bone mineral density (BMD) measurement with single-energy X-ray
      absorptiometry (SXA) of the distal forearm, and dual-energy X-ray absorptiometry
      (DXA) of the lumbar spine, proximal femur and distal forearm. In a random
      subgroup of 308 women, aged 45-60 years, on average 6 years since menopause
      (YSM), bone densitometry was measured once at baseline by RA of the phalanges
      besides the mandatory measurements by DXA. Bone densitometry was furthermore
      measured by SXA at the Danish site (89 women). Sixty-eight of the women had
      duplicate measurements performed within 1-3 weeks to evaluate the short-term
      precision error (CV%). One hundred and one healthy premenopausal women, aged 25
      48 years, were recruited at the Danish and Hawaiian sites to establish a
      reference group. The precision error was 1.5% for RA of the phalanges and in the
      range 1.0-2.2% for SXA and DXA. BMD by RA correlated with BMD measured by SXA and
      DXA in the range 0.45 < r < 0.72 (p < 0.001). In conclusion, bone densitometry by
      RA of the phalanges is highly correlated with bone densitometry by SXA and DXA.
      RA of the phalanges has a short-term precision error comparable to that of SXA
      and DXA.

PMID- 8883122
TI  - Variability of vertebral and femoral postmenopausal bone loss: a longitudinal
      study.
AB  - The rate of postmenopausal bone loss varies considerably between individuals and
      it has been suggested that about 1 in 3 women loses significant amount of bone
      mineral in the forearm. The rate of vertebral and femoral bone loss was
      determined by dual-energy X-ray absorptiometry throughout two consecutive 22
      month periods, in 93 healthy women who had passed a natural menopause 6-60 months
      earlier. In all cases the bone changes were normally distributed, ranging from 
      6.9% to +2.8% per year in the spine and from -7% to +4.8% per year in the femur.
      No significant relationship was found between the two fractional rates of bone
      loss. When the women were stratified into three groups according to their
      individual rate of bone loss, we found that only 20%-47% retained their first
      classification during the second period of follow-up. In particular, less than
      10% of the women showed a rapid rate of bone loss throughout the study. We
      conclude that spontaneous vertebral and femoral bone loss exhibit a great
      variability within the first postmenopausal years and that only a small minority
      of women sustain a fast rate of bone loss over several years. These results raise
      the question as to whether the evaluation of individual rates of bone loss at
      menopause might be useful in the identification of women at higher risk of
      osteoporosis.

PMID- 8883123
TI  - An anthropological perspective on optimizing calcium consumption for the
      prevention of osteoporosis.

PMID- 8883124
TI  - Estrogen replacement may be an alternative to parathyroid surgery for the
      treatment of osteoporosis in elderly postmenopausal women presenting with primary
      hyperparathyroidism: a preliminary report.
AB  - Parathyroid surgery is indicated in patients presenting with primary
      hyperparathyroidism (PHPT) and osteoporosis (defined as bone mineral density more
      than 2 standard deviations below normal). Many are elderly women with complex
      medical problems, either unwilling or considered unfit for surgery. Estrogen
      replacement therapy (ERT) may potentially be an alternative form of therapy in
      this group. We studied 15 consecutive postmenopausal women presenting with PHPT
      and osteoporosis. Group 1 comprised 5 women who elected to be treated with ERT
      (conjugated equine estrogen, 0.3-0.625 mg/day). The other 10 women underwent
      successful parathyroidectomy. These 10 patients were randomly subdivided into
      group 2 (5 patients who received calcitriol 0.25 micrograms b.i.d. for 12 months
      following surgery) and group 3 (5 patients who received elemental calcium 1 g/day
      for 12 months following surgery). Lumbar spine and femoral neck bone mineral
      density (BMD) were measured prior to and after 12 months of therapy, using a dual
      energy X-ray absorptiometer (Lunar DPX-L). The three groups did not differ with
      respect to their ages (group mean 71.8 years), or baseline serum calcium (group
      mean 2.77 mmol/l), serum parathyroid hormone (group mean 11.0 pmol/l), lumbar
      spine BMD (group mean 0.93 g/cm2) and femoral neck BMD (group mean 0.73 g/cm2).
      Serum calcium normalized in all patients who underwent surgery and none developed
      hypoparathyroidism. A non-significant decrease in serum calcium was seen in
      patients treated with ERT only. Lumbar spine (+5.3% per year; 95% CI, 1.1% to
      9.6%) and femoral neck BMD (+5.5% per year; 95% CI, -2.1% to 13.2%) increased
      significantly after 12 months of ERT (p < 0.001 compared with pre-therapy
      values). These increases in BMD did not differ significantly from those in
      patients who underwent successful parathyroidectomy followed by either calcitriol
      therapy or calcium replacement (lumbar spine BMD increase of +6.2% per year, 95%
      CI 3.1% to 9.4%; and femoral neck BMD increase of +3% per year, 95% CI 0 to 6%).
      In summary, increases in lumbar spine and femoral neck BMD occur following
      treatment of PHPT. ERT appeared as effective as parathyroidectomy (combined with
      either calcitriol or calcium supplements) for the treatment of osteoporosis in
      elderly postmenopausal women presenting with PHPT.

PMID- 8883125
TI  - Polymorphisms of the vitamin D receptor gene do not predict quantitative
      ultrasound of the calcaneus or hip axis length.
AB  - Quantitative ultrasound of the calcaneus and hip axis length are independent
      predictors of hip fracture and have a major genetic component. Polymorphisms of
      the vitamin D receptor gene (VDR) have been associated with variations in bone
      density in a number of studies. The aim of this study was to examine the role of
      VDR on other parameters associated with the risk of fracture. One hundred and
      eighty-nine pairs of healthy female dizygous twins were genotyped and had
      calcaneal ultrasound (broadband ultrasound attenuation and velocity of sound) and
      hip axis length measurements performed. Twin analysis using intraclass
      correlation coefficients and intrapair differences failed to find an association
      between the VDR polymorphisms and hip axis length or calcaneal ultrasound.
      Analysing the twins as a population, irrespective of twinning, also failed to
      find any association. The search for alternative genes influencing bone fragility
      should continue as a research priority.

PMID- 8883126
TI  - Spontaneous multiple vertebral fractures revealed primary haemochromatosis.
AB  - The association of haemochromatosis and bone disease is well established, but
      osteoporotic fracture is an unusual presentation of the disease. We describe a
      male patient with osteoporotic fractures as a presenting feature of
      haemochromatosis. The bone histomorphometry showed a dramatic decrease in
      trabecular bone volume associated with a decrease in cortical bone thickness.
      Osteoblastic and osteoclastic activities were reduced without any sign of
      osteomalacia. Staining for iron with Perl's stain showed focal localization at
      the interface between mineralized trabecular bone and bone marrow. This
      observation leads us to review the possible mechanisms of osteoporosis.

PMID- 8883127
TI  - Assessment of bone density and bone loss.

PMID- 8883128
TI  - Rationale and clinical indications for bone density measurements.

PMID- 8883129
TI  - Establishing an osteoporosis service.

PMID- 8883130
TI  - The impact of mitigating the effect of age-related diseases, such as
      osteoporosis.

PMID- 8883131
TI  - The cost of treating hip fractures in the twenty-first century: short report.

PMID- 8883132
TI  - Role and evolution of therapeutic options.

PMID- 8883133
TI  - Alendronate--a new bisphosphonate.

PMID- 8883134
TI  - Establishing a hospital specialist osteoporosis service.

PMID- 8883135
TI  - Providing a primary care open access clinic for osteoporosis.

PMID- 8883136
TI  - Audit in osteoporosis.

PMID- 8883141
TI  - Development and applications of the SCID-hu mouse model.
AB  - The SCID-hu mouse was designed to serve as a preclinical model for the analysis
      of human physiology and pathophysiology. In distinction to other immunodeficient
      mouse models, SCID-hu mice are made upon implantation of intact human organ
      systems rather than dispersed cell populations. Two constructs, the SCID-hu
      Thy/Liv and the SCID-hu Bone models, have been developed to reproduce the
      differentiation and function of human hematopoietic progenitor cells within the
      human thymus and bone marrow microenvironments, respectively. This review focuses
      on several applications of these models: definition of multilineage and lineage
      restricted human hematopoietic progenitor cells and evaluation of HIV disease and
      its treatment.

PMID- 8883142
TI  - Normal and leukemic human stem cells assayed in SCID mice.
AB  - Understanding the processes that regulate the developmental program of normal
      stem cells and those that initiate proliferative diseases such as leukemia
      remains one of the major challenges in biology. Progress to address these major
      questions in the human hematopoietic system have been hampered, until recently,
      by the lack of in-vivo assays for normal and leukemic stem cells. The recent
      development of methods to transplant normal and leukemic human hematopoietic
      cells into immune-deficient mice provides an important approach to identify,
      characterize and purify stem cells. This review will focus on the development of
      assays for normal and leukemic human stem cells and on the new insights these
      assays are beginning to provide on the organization of the human stem cell
      hierarchy and mechanisms of leukemogenesis.

PMID- 8883143
TI  - Human T-and B-cell functions in SCID-hu mice.
AB  - SCID mice transplanted with human fetal liver and thymus (SCID-hu Thy/Liv)
      provide a unique in-vivo model to study human T-cell development and clonal
      selection mechanisms. This SCID-hu mouse model can be adapted to study the role
      of thymic epithelial cells, or bone marrow-derived cells in transplantation
      tolerance. In addition, these mice have circulating human T cells, which mediate
      human allograft rejection in vivo. SCID-hu mice constructed with fetal bones and
      thymus (SCID-hu BM/Thy) have both circulating human T and B cells, and can be
      used to study human B-cell development and B-cell functions. In addition, human T
      B-cell interactions resulting in human lg production and the modulating effects
      of cytokines and cytokine receptor antagonists on this process, can be monitored.
      Collectively, this information indicates that the SCID-hu mouse is a powerful and
      versatile model to study human immune responses in vivo.

PMID- 8883144
TI  - The SCID-hu mouse: an in-vivo model for HIV-1 pathogenesis and stem cell gene
      therapy for AIDS.
AB  - Animal models are critical to the investigation of human immunodeficiency virus
      type 1 (HIV-1) pathogenesis. However, normal animal models are either
      uninfectable with HIV-1, or if infected, do not display HIV-1 induced pathology.
      Here, we describe how the severe combined immunodeficient mouse (SCID), implanted
      with human fetal thymus and liver, has been used to model HIV-1 pathogenesis and
      anti-retroviral gene therapy. Unable to reject the human tissue, these chimeric
      mice provide the investigator with a human hematolymphoid organ which, following
      infection by HIV-1, may more closely mimic the situation seen in humans than
      standard in-vitro culture systems.

PMID- 8883145
TI  - SCID-hu mice: a model for studying disseminated HIV infection.
AB  - Modifications that we introduced into the implantation of human fetal thymus and
      liver into SCID mice (thy/liv-SCID-hu mice) markedly increased the population of
      human T cells and monocytes present in the peripheral blood and peripheral
      lymphoid compartment of these mice. As a result, the modified thy/liv-SCID-hu
      mice developed disseminated HIV infection after intraimplant or i.p. inoculation.
      After chronic HIV infection of these mice, depletion of the peripheral human T
      cells was observed as reported in HIV-infected individuals. In addition, these
      mice also developed plasma viremia after infection with HIV. The peripheral blood
      mononuclear cells were responsive to in-vivo cytokine regulation as evidenced by
      induction of human IFN-gamma gene expression by human IL-12 and inhibition by
      human IL-10. Acute treatment with human IL-10 but not with human IL-12 inhibited
      the development of plasma viremia and HIV infection in thy/liv-SCID-hu mice
      inoculated with HIV-1(59), a clinical isolate. SCID mice transplanted with
      cultured human fetal bone marrow displayed significant engraftment of the mouse
      bone marrow with human precursor cells and population of the peripheral blood
      with human B cells and monocytes. The peripheral blood of these bone marrow
      transplanted SCID mice also became populated with human T cells after they were
      implanted with human thymic tissue due to migration of human precursor cells from
      the mouse bone marrow to the implanted human thymus. Thus, these modified SCID-hu
      mice should prove to be a valuable in-vivo model for studying the
      immunopathogenesis of HIV infection and for examining the in-vivo efficacy of
      immunomodulatory, drug and gene therapy in modifying HIV infection.

PMID- 8883146
TI  - The huPBL-SCID mouse as a means to examine human immune function in vivo.
AB  - The transfer of human peripheral blood lymphocytes (huPBL) into mice with severe
      combined immune deficiency (SCID) has allowed for the generation of a model in
      which it is possible to examine human immune cell function in vivo. This model
      also provides the researcher an invaluable tool with which to examine human
      disease states and to evaluate potential therapies using human cells and reagents
      under more physiological conditions. However, it is clear that there are still
      significant obstacles that need to be addressed to optimize this model. The
      primary problem with the huPBL-SCID mouse is the tremendous variability in the
      extent of human cell engraftment which can vary from donor to donor and even from
      mouse to mouse using the same huPBL donor. This variability currently limits
      attempts to standardize this model among investigators and subsequently, various
      laboratories have employed different methods to optimize and ascertain the extent
      of human cell engraftment. In addition, there appears to be significant
      xenogeneic host-versus-graft and graft-versus-host reactions, as well as lethal
      EBV-induced B-cell lymphomas that can spontaneously arise which may further
      complicate the interpretation of human immunological studies performed in these
      mice. Despite these obstacles, the huPBL-SCID model has the potential to serve as
      a model for the examination of human lymphoid cells in an in-vivo setting and has
      been usefully applied to the study of various human disease states including
      AIDS, transplantations, autoimmunity and cancer.

PMID- 8883147
TI  - SCID-hu-PBL: a model for making human antibodies?
AB  - The ability of SCID mice to accept xenografts has been utilized in the search for
      a laboratory model that mimics the human immune system. Intraperitoneal injection
      of human peripheral blood lymphocytes into SCID mice constitutes a feasible and
      easy way of establishing an experimental immune system that may be manipulated
      without the concern that applies to human volunteers. Of particular interest to
      the immunotechnologists is the possibility of utilizing SCID-human chimeras to
      generate a human affinity maturated IgG response, which could form the basis for
      the development of therapeutic antibodies. This review discusses some of the
      potential limitations of SCID-hu-PBL chimeras in achieving this goal.

PMID- 8883148
TI  - The hu-PBL-SCID mouse in human lymphocyte function and lymphomagenesis studies:
      achievements and caveats.
AB  - The chance isolation of a mouse strain mutant that shows a complete deficiency in
      both the humoral and cellular immunity compartments has opened new perspectives
      in numerous fields of medicine and biology, including oncology, hematology and
      immunology. However, the original concept that the severe combined
      immunodeficiency mouse might behave as a 'living vessel', and allow experimental
      approaches that are precluded in man by technical and ethical constraints, has
      not fully withstood the test of time. At present, despite the body of important
      results achieved in the past few years, the use of this model in some areas is
      somewhat deregulated; no standard protocols are available, and some critical
      variables that could affect experimental results are not always under control. In
      this article, we have focused on the use of the SCID mouse reconstituted with
      human mature lymphoid cells in immunological studies, and tried to enucleate, in
      the array of existing experimental work, some basic concepts that might favor
      more judicious and appropriate approaches to the use of this important
      experimental model.

PMID- 8883149
TI  - Viral pathogenesis in hu-PBL-SCID mice.
AB  - The transplantation of human cells into immunodeficient mice has provided new
      models for human immune function, infection by pathogenic viruses that grow in
      lymphocytes or other hematopoietic cells, and development of hematopoietic
      lineages. SCID mice reconstituted with adult peripheral blood mononuclear cells
      (hu-PBL-SCID mice) maintain some established immune responses, but do not produce
      a full spectrum of primary cellular or humoral responses. Nonetheless, hu-PBL
      SCID mice are a valuable tool for studying primary infection with human
      immunodeficiency virus (HIV) and reactivation of latent Epstein-Barr virus (EBV)
      infection. This review will summarize findings from such studies.

PMID- 8883150
TI  - Defining antibody protection against HIV-1 transmission in Hu-PBL-SCID mice.
AB  - Multiple monoclonal and polyclonal antibody preparations have been shown to
      neutralize HIV-1 infection in vitro. Upon direct testing in humans, however, many
      of these have failed to demonstrate clinical efficacy. Hu-PBL-SCID mice offer a
      model system in which to test the pre-clinical efficacy of antibody preparations.
      Testing in hu-PBL-SCID mice has shown that some antibodies are able to mediate
      pre- and post-exposure protection against HIV-1 infection, at concentrations that
      should be attainable in humans. Despite differences in the route and mode of
      transmission in humans and in hu-PBL-SCID mice, several aspects of the model make
      it a favorable model for future testing of antibody protection against HIV-1
      infection. These include the architecture of the peritoneal cavity, the mixture
      of human cells that engraft, the density of human target cells for HIV-1
      infection, and the presence of complement and NK cells that can interact with
      antibody preparations in blocking HIV-1 infection. The use of this model in
      testing newer antibody preparations for efficacy against primary isolates should
      enhance our knowledge of the mechanisms of antibody protection against HIV-1
      infection in vivo and speed the pre-clinical evaluation of potential
      immunoprophylactic agents against HIV-1.

PMID- 8883151
TI  - Acute hemichorea in a 14-year-old boy.
AB  - The differential diagnosis of chorea or hemichorea in an adolescent boy is
      discussed. Sydenham's chorea, still the most common cause of chorea in childhood,
      is only one of many important diseases in the differential diagnosis in this
      clinical situation.

PMID- 8883152
TI  - Excessive daytime sleepiness in a 13-year-old.
AB  - Included in the large group of children referred for attention deficit
      evaluations, several less common entities can be found. Careful history will
      enable the identification of these atypical cases of attention deficit and allow
      more precise diagnosis and treatment.

PMID- 8883153
TI  - Acquired immobility of the right arm.
AB  - The occurrence of an asymmetrical motor dysfunction is an event that frequently
      results in referral to the pediatric neurologist. The differential diagnosis is
      not extensive but is somewhat larger than superficial evaluation might indicate.
      This 4-year-old boy developed intermittent painful motor dysfunction of the right
      arm over a 1-year period of time resulting from an unusual cause of unilateral
      motor dysfunction.

PMID- 8883154
TI  - Mental retardation plus macrocephaly in a 16-year-old boy.
AB  - The evaluation of mental retardation is a frequent and challenging problem in
      pediatric neurology. Often clues obtained on history or by physical examination
      will help to direct the evaluation in the appropriate channel. This 16-year-old
      boy had clinical features which suggested the appropriate diagnostic studies.

PMID- 8883155
TI  - Partial complex seizures in an 11-year-old girl.
AB  - Partial complex seizures are often refractory to antiepileptic medications and
      may require epilepsy surgery for control. With the use of contemporary
      neuroimaging techniques the number of children with "idiopathic" partial complex
      seizures has declined. A presurgical neuroimaging evaluation for refractory
      partial complex seizures is discussed.

PMID- 8883156
TI  - Focal status epilepticus and hemiparesis in an 8-year-old boy.
AB  - An afebrile child with focal status epilepticus and an altered mental status
      presents a diagnostic and therapeutic challenge. Traditional morphological
      neuroimaging may be of limited value in the evaluation of such patients, and one
      may have to rely more upon functional neuroimaging studies. Recent advances in
      the understanding of the pathogenesis and the role of functional neuroimaging
      studies in the evaluation of focal status epilepticus are discussed.

PMID- 8883157
TI  - Increasing irritability with sudden onset of flaccid weakness.
AB  - Spontaneous spinal epidural hematoma (SSEH), is a rare and potentially fatal
      condition that responds favorably to early surgical intervention and should be
      considered in the differential diagnosis of spinal cord compression. There are
      few reported cases in children. We present a case of spontaneous spinal epidural
      hematoma in an 18-month-old child and review the literature.

PMID- 8883158
TI  - Sudden attacks of head pain in a young child.
AB  - In the evaluation of headaches at any age, the clinical features of the episodes
      are the most important diagnostic information available. In the patient
      presented, the nature of the headaches suggests the need for further study as
      well as the most fruitful location in which to look.

PMID- 8883159
TI  - Progressive spasticity in an infant.
AB  - A 15-month-old girl with progressive spasticity presented for evaluation of
      cerebral palsy. Neurological examination revealed severe asymmetric spasticity
      with normal cranial nerves. Bayley developmental assessment showed a mental age
      of 12 months and a motor age of 9 months. Magnetic resonance imaging scan of the
      brain was normal, however a scan of the cervical spine showed an enhancing
      intramedullary lesion. Surgical exploration revealed an aneurysm which was
      successfully embolized. The differential diagnosis of cervical cord lesions in
      infants is discussed.

PMID- 8883160
TI  - Atypical idiopathic scoliosis in childhood.
AB  - Scoliosis, common in preadolescent females is a finding which warrants
      investigation in any other age group or if the clinical or neuroimaging features
      are atypical even in the preadolescent female. The cause of scoliosis are
      numerous but include several important conditions some of which are treatable and
      some of which are genetic. A rational approach to sequencing the neuroimaging
      studies to be used is based on what the clinical suspicions are and the results
      of the initial studies.

PMID- 8883161
TI  - Progressive degenerative disorder of the central nervous system.
AB  - The child with a deteriorating course is a regular if not common clinical problem
      for the child neurologist. An apparent plateau in the course can often be
      confusing if the focus is limited to the current visit. With the explosion of
      information and understanding of molecular genetics, failure to recognize the
      presence of a degenerative disease may have significant consequences for the
      family of the patient and possibly the patient as well.

PMID- 8883162
TI  - Neck pain and headache in an afebrile 15-year-old.
AB  - Nuchal rigidity and headache are important signs of bacterial meningitis,
      although, in the absence of fever other etiologies would be considered. An
      evaluation of a 15-year-old boy with the above features, focal neurological
      deficits, and two cerebral contrast enhancing ring lesions is discussed.

PMID- 8883163
TI  - Recurrent coma.
AB  - Recurrent episodes of coma are usually associated with a metabolic disorder. A
      healthy 9-year-old boy of normal intellect and intact corpus callosum on
      neuroimaging had recurrent episodes of coma associated with profound spontaneous
      hypothermia. An evaluation, differential diagnosis and insights into the
      pathogenesis of this disorder are discussed.

PMID- 8883164
TI  - Headaches of recent onset and long-term learning disability.
AB  - In the evaluation of headaches, history is everything! Usually. However,
      sometimes the headaches are associated with unrelated conditions simply because
      of their frequency. The evaluation of a child with a learning disability is also
      a common exercise and the trick, with both conditions, is to recognize the
      occasional patient who warrants further evaluation.

PMID- 8883165
TI  - Agenesis of corpus callosum.
AB  - This 20-month-old girl was found to have an abdominal mass. She was known to have
      an 8p + karyotype with multiple congenital anomalies including the Pierre Robin
      sequence. Computed tomography disclosed agenesis of the corpus callosum. The
      child died following resection of a nephroblastoma. The neuropathological
      findings are illustrated and discussed.

PMID- 8883166
TI  - Neurological features of perinatal asphyxia: a clinical and pathological study of
      a neonate with multicystic encephalopathy.
AB  - This male infant suffered severe perinatal asphyxia resulting in multicystic
      encephalopathy. The various clinical observations and laboratory studies
      performed on this child are discussed with reference to their use in determining
      the severity of hypoxic-ischemic encephalopathy and predicting long-term
      outcomes.

PMID- 8883167
TI  - Failure to thrive, hepatic dysfunction, hypotonia, and cerebellar atrophy.
AB  - A 2-year-old with cerebrellar and gastrointestinal difficulties is presented. The
      differential diagnosis of this combination of clinical features is difficult but
      recently several of the conditions under consideration have been more precisely
      characterized from a molecular standpoint.

PMID- 8883168
TI  - Altered consciousness and shock in a malnourished child.
AB  - A 3-year 9-month-old child presented unresponsive, dehydrated, and in shock, a
      consequence of child neglect, abuse, and starvation. This scenario provides the
      vehicle for a discussion of three problems which can be precipitated by child
      neglect, specifically kwashiorkor, central pontine myelinolysis, and intellectual
      repercussions of malnutrition.

PMID- 8883169
TI  - Paroxysmal torticollis.
AB  - An infant with recurrent episodes of torticollis lasting several hours at a time
      is presented. The diagnosis is primarily one of pattern recognition and exclusion
      of alternative diagnoses.

PMID- 8883170
TI  - Diagnostic approach to pneumonia in children.
AB  - Pneumonia in children may be caused by a variety of agents each requiring a
      different treatment approach. Lack of a simple and reliable method for
      establishing an etiologic diagnosis in most cases forces the physician to make
      therapeutic decisions based on the age of the patient, clinical presentation,
      radiographic findings, and the knowledge of the likely organisms. When a more
      specific diagnosis is sought, several noninvasive and invasive techniques are
      available. Among the first group are sputum examination, cultures of blood,
      sputum and respiratory tract specimens, rapid antigen detection tests, and
      serology. Those in the later group, which is usually reserved for critically ill
      patients or those with underlying immunodeficiency, include pleurocentesis,
      bronchoalveolar lavage, transbronchial biopsy, and open-lung biopsy. The
      indications and potential advantages of these tests are discussed in this review.

PMID- 8883171
TI  - Antimicrobial therapy of pneumonia in infants and children.
AB  - To provide optimal management for the child with community-acquired pneumonia,
      the clinician must take multiple factors into consideration. The etiology of
      pneumonia is difficult to determine and initial choice of therapy is based on the
      frequency of pathogens in various age groups, local antibiotic resistance
      patterns of the organisms, clinical presentation, and epidemiological data.
      Streptococcus pneumoniae and Haemophilus influenzae remain the most common
      bacterial pathogens outside the newborn period. Increasing numbers of multidrug
      resistant strains of S pneumoniae in the United States and Europe, the decline in
      H influenzae type b because of current vaccination strategies, and increasing
      recognition of nontypeable H influenzae as etiologic agents of pneumonia have
      prompted reconsideration of the drug of choice. Amoxicillin and its derivatives
      or oral cephalosporins are the drugs of choice for initial therapy for mild to
      moderate disease. For severe disease or if beta-lactamase producing organisms are
      a concern, extended spectrum cephalosporins are indicated. Pneumococcal pneumonia
      unresponsive to penicillin therapy may warrant the use of extended spectrum
      cephalosporins or vancomycin. For older children in whom mycoplasma is a
      significant cause of pneumonia, the new macrolides have provided additional
      options for the clinician. Azithromycin and clarithromycin are efficacious, well
      tolerated, and require less frequent dosing intervals. The introduction of
      ceftriaxone, a third-generation cephalosporin with a broad spectrum of activity
      and prolonged half-life, allows once-a-day intramuscular therapy that can be
      administered on an outpatient basis. With the availability of parenteral
      outpatient therapy, hospital admission is no longer required for the treatment of
      most cases of serious community-acquired pneumonia.

PMID- 8883172
TI  - Pleural infection in children.
AB  - The physiology of pleural liquid formation and stages of pleural effusion are
      reviewed in this article in our recent experience, only 50% of pleural effusions
      in hospitalized patients were parapneumonic and only about 7% of these patients
      could be classified as having an empyema. These findings are in contrast to
      children 20 to 30 years ago in whom over 40% of parapneumonic effusions were
      empyemas. Diagnostic approaches are also controversial. The accuracy, sensitivity
      and specificity of various biochemical tests of pleural fluid have not been
      assessed in children. It seems reasonable to avoid thoracentesis if the clinician
      is certain of etiology of the pleural effusion from the history, physical
      examination, and supporting laboratory data. Treatment is also controversial.
      Indeed, most patients recover without tube thoracostomy. In our series, only 27%
      of patients were treated with tube drainage. It is suggested that drainage is
      necessary to relieve respiratory difficulty or pleuritic pain when effusions are
      relatively large. The need to drain all empyemas is also a controversial issue
      both in the child and adult. Clearly, what is needed is a carefully designed
      multicentered prospective study of pleural effusion in children.

PMID- 8883173
TI  - Neonatal pneumonia.
AB  - Respiratory infections in young infants are common and can cause significant
      morbidity and mortality. The etiology of pneumonia in the neonate varies widely
      because of several modes of acquisition of infecting agents. Infants may develop
      pneumonia in utero as a part of a congenital infection; however, more often,
      infants are exposed to potential pathogens in the perinatal and postnatal
      periods. The management of neonates with pneumonia should include diagnostic
      evaluation and empiric therapy directed at the organisms commonly found in the
      maternal genital tract, and respiratory pathogens found in the community. For
      premature or critically ill term infants in neonatal intensive care units, one
      must consider the multitude of nosocomial pathogens that colonize and cause
      invasive disease in these immunocompromised hosts.

PMID- 8883174
TI  - Chest infections and syndromes in sickle cell disease of childhood.
AB  - Sickle cell lung disease occurs in all of the more common sickle
      hemoglobinopathies. Of the acute pulmonary diseases, acute chest syndrome (ACS)
      is most common. The risk of recurrence after one episode of ACS ranges from 20%
      to 80%. Repeated episodes of ACS contribute to the development of earlier and
      potentially rapid pulmonary deterioration particularly in young adults. ACS is
      the second most common cause for hospital admission and has been reported to be
      responsible for 25% of sickle cell deaths. The exact etiology of ACS may be
      unclear and is often caused by the interaction of a number of factors. Although
      infection is most likely in the young child, infarction and thromboembolism are
      the more likely causes in older patients. Outcome is dependent on immediate
      recognition and rapid institution of therapy. Maintenance of adequate oxygenation
      treatment of possible underlying infection, and adequate hemoglobin delivery are
      essential. Simple or exchange transfusion is vital to improve hemoglobin delivery
      and decrease hemoglobin S concentration. Caution is advised when administering
      drugs such as morphine for pain control because of risk of exacerbation of
      pulmonary symptomatology.

PMID- 8883175
TI  - Human immunodeficiency-virus-related pulmonary infections in children.
AB  - Increasing numbers of children with human immunodeficiency virus (HIV) infection
      continue to be seen in the United States. Pulmonary infections constitute a major
      cause of morbidity and mortality in these children Pneumoncystis carinii
      pneumonia, pulmonary lymphoid hyperplasia/lymphoid interstitial pneumonitis, and
      bacterial pneumonias, all described in high frequency in the earliest cases of
      pediatric acquired immunodeficiency syndrome, remain the pulmonary diseases
      confronted most often. Other pathogens, such as Mycobacterium tuberculosis and
      respiratory virus infections are now being identified in increasing numbers in
      HIV-infected children. Advances in our understanding of these disease processes
      and their clinical manifestations have allowed development of a systematic
      approaches to the common problem of the HIV-infected child with fever, tachypnea,
      and hypoxemia and an abnormal chest radiograph. These approaches, coupled with
      improvements in available treatment options, have led to earlier diagnosis and
      improved survival. Prophylaxis strategies have been developed for the most
      serious pulmonary infections, especially P carinii pneumonia. However, lack of
      identification of infants and children at risk of HIV infection has limited their
      effectiveness. Pulmonary infections in HIV-infected children continue to take a
      high toll with regard to morbidity and mortality. Only with continued advances in
      primary therapy to slow progression of the underlying immunodeficiency and
      widespread use of available prophylactic guidelines will these be reduced.

PMID- 8883176
TI  - Intrathoracic tuberculosis in children.
AB  - After decades of decline, tuberculosis case rates are increasing again in the
      United States. Primarily because of increases in tuberculosis among persons of
      child-bearing years and diminished performance by some health departments,
      substantial increases in reported cases of tuberculosis in children have occurred
      since 1985. Although the clinical/radiographic presentation of intrathoracic
      tuberculosis in children has not changed significantly, major changes have
      occurred in the treatment of tuberculous disease over the past decade. This
      article will review the current epidemiology, diagnosis, and treatment of
      childhood tuberculosis.

PMID- 8883177
TI  - Community-acquired fungal pneumonia in children.
AB  - Pediatric fungal pulmonary infections are being seen with increasing frequency.
      The dimorphic fungi Histoplasma capsulatum. Blastomyces dermatitidis,
      Coccidioides immitis, and Cryptococcus neoformans frequently cause infections
      that are asymptomatic. However, patients may suffer pneumonia and disseminated
      disease. Diagnosis can be made definitively by isolation of the causative
      organism, but serology or skin testing is often necessary when this is not
      successful. Severe or life threatening infections are treated with amphotericin
      B. Recently, new oral azole antifungals are being used more frequently for mild
      to moderate disease with good success.

PMID- 8883178
TI  - Foolers: things that look like pneumonia in children.
AB  - Pulmonary infiltrates on chest radiographs are common findings in the pediatric
      age group and are generally associated with acute infectious pneumonias.
      Occasionally, however, these "pneumonias" fail to respond to appropriate
      antibiotic therapy. Under these circumstances, noninfectious conditions that may
      be associated with pulmonary infiltrates should be considered. Thus, it is
      important that physicians who care for children have some knowledge of these
      potential "mimickers" of childhood pneumonia.

PMID- 8883179
TI  - Social work with transport disabled persons: a wayfinding perspective in health
      care.
AB  - Transport disabled persons confront extensive architectural and psychosocial
      barriers during their travel to community based health care services by mass
      transit. The current health care reform movement affords social work an
      opportunity to consolidate its expertise with this population. The Certificate of
      Need program is a method with which social work can provide service to people
      with transportation disabilities. Social work can also continue its use of the
      Americans with Disabilities Act and the Urban Mass Transportation Act to assist
      people with transport disabilities to access community based health care
      services.

PMID- 8883180
TI  - Successful living placement for adults with disabilities: considerations for
      social work practice.
AB  - This article presents a study which was implemented to investigate successful
      community living in rural non-elders with chronic physical disabilities. Based on
      the results of an initial naturalistic study, a survey design was used to
      identify factors which distinguish persons with disabilities between the ages of
      16-65 in institutional settings from their counterparts in community-based
      settings. The findings revealed significant differences in desire for autonomy,
      satisfaction with participation in the level of decision making around living
      environment, knowledge of community living and service options, fear of being
      alone in the community, support from family and personal care assistance in the
      community and socialization patterns. Yet no significant differences in
      functional status or need for assistance in activities of daily living was noted
      between the groups. The study suggests that living placement is not a function of
      medical or activities of daily living assistance need, but rather is a complex
      phenomenon comprised of numerous personal, social, resource and environmental
      factors.

PMID- 8883181
TI  - The impact of a client's diagnosis of AIDS on social workers' clinical
      judgements: an experimental study.
AB  - This article reports the findings and implications of a study in which the effect
      of the AIDS diagnosis, alone and in interaction with a client's race, gender and
      sexual orientation, on social workers' clinical assessments was determined. The
      study utilized a constructed case history in which all information about the
      client was held constant except for his or her race (African-American or white),
      gender, sexual orientation and terminal diagnosis (AIDS or heart condition).
      Licensed social workers in one state were randomly selected and sent one case
      history as well as a questionnaire which required them to provide clinical
      assessments of the hypothetical client as well as information about themselves
      and their evaluations of their ability to be helpful to the client. Results
      indicate that respondents believed that a variety of treatment options were
      necessary if the client they had read about had AIDS. Further, they reported
      feeling uncomfortable and ill-prepared to work with such a client. The
      interaction effects of the AIDS diagnosis and the client's race, gender, and
      sexual orientation also influenced several dependent measures.

PMID- 8883182
TI  - Searching for information, understanding, and self-value: the utilization of peer
      support groups by gay men with HIV/AIDS.
AB  - The present study examined the patterns and variations characterizing the support
      group involvements of 25 gay men with HIV/AIDS. Results indicated that those men
      who participated in support groups on a long-term basis (i.e., one year or more)
      were less likely to have access to other social support networks. They were also
      most interested in receiving and exchanging emotionally-oriented forms of
      support, such as empathy, acceptance and camaraderie. By contrast, the men who
      participated in support groups for a brief period of time (i.e., six months or
      less) had greater access to alternative support networks and were more interested
      in receiving and exchanging instrumental forms of support, such as illness
      related information and examples of effective coping. Those men who elected not
      to participate in support groups emphasized their relatively good health, the
      strength of their existing support systems and their reluctance to see others
      with life-threatening symptoms. Finally, regardless of whether and how they
      participated in formal support groups, the majority of men in this study
      benefitted from interacting regularly with peers. Through these interactions,
      they received helpful understanding, information and friendship. In addition to
      this, they often experienced a revitalizing sense of purpose, efficacy and
      mutuality which enabled them to cope more successfully with their illness.

PMID- 8883183
TI  - Themes from the frontlines: hospital social work with people with AIDS.
AB  - There is little in the literature that specifically explores challenges and
      perceived rewards faced by direct care social work practitioners who work with an
      inpatient AIDS population, although there are hints (Egan, 1993, Oktay, 1992, and
      Gilmann, 1991). This article, based on a study of 20 designated inpatient AIDS
      social workers at four large inner-city voluntary hospitals, will focus on
      challenges and rewards as perceived by social work practitioners working with the
      HIV infected population. The study will report commonly identified themes which
      include unique stressors, rewards and challenges experienced by social work
      practitioners working with those living with AIDS.

PMID- 8883184
TI  - Breaking the bad news when sudden death occurs.
AB  - Notification of family when sudden death has occurred is often a highly stressful
      experience for hospital Emergency Department physicians and nursing personnel.
      This article will offer some guidelines to health care professionals in helping a
      deceased patient's family cope with the initial grief and loss that accompanies
      the unexpected death of a loved one. At the same time, an understanding of the
      wide range of emotional responses of bereaved survivors may case some of the
      anxiety Emergency Department staff members associate with "breaking the bad
      news."

PMID- 8883185
TI  - Paraplegic locomotion: a review.

PMID- 8883186
TI  - Evaluation of client and staff satisfaction with a Goal Planning project
      implemented with people with spinal cord injuries.
AB  - This study assesses client satisfaction and canvasses staff opinions concerning
      the first year of a Goal Planning rehabilitation programme implemented with in
      patients who had sustained a severe spinal cord injury. Questionnaires were
      completed by 33 patients. As a keyworker system is an integral part of Goal
      Planning, separate questionnaires were completed by 13 staff/keyworkers. The
      results indicated that patients believed Goal Planning to be informative about
      their injury and helpful in promoting a sense of control over their
      rehabilitation. In addition, a positive, and statistically significant
      association was found between perceived informativeness and control and the
      implications for successful rehabilitation are considered. Staff also gave
      favourable feedback regarding the perceived benefits of Goal Planning for
      patients, relatives and staff, although they acknowledged the resulting increase
      in their workload.

PMID- 8883187
TI  - Functional assessment of patients with spinal cord injury: measured by the motor
      score and the Functional Independence Measure.
AB  - There is some information about the Functional Independence Measure (FIM) score
      of patients with spinal cord injury (SCI), but there are a few publications
      dealing with the relationship between the FIM score and the motor score of the
      American Spinal Injury Association (ASIA). We have studied the relationship of
      all FIM items with the motor score, and reviewed the disability of patients with
      spinal cord injury in greater detail. The purpose of this study was to describe
      the characteristics of impairment and disability in patients with SCI, using the
      FIM and motor score of the ASIA. The subjects were 100 inpatients with SCI
      (Frankel A, B). Neurological level, days from the onset, and the FIM were
      examined. In addition to these items, the ASIA motor scores were calculated for
      22 tetraplegic patients. We investigated the relationships among these various
      respects. We also examined the changes of the physical items of the FIM score
      (physical FIM) over time for 18 patients. The mean FIM scores of those with
      tetraplegia with C4, C5, C6, C7, C8 lesions, and those with paraplegia with above
      T5 levels, and those below T6 were 35, 61, 82, 90, 116, 114 and 114 respectively.
      The FIM score reached the plateau in approximately 10 months, 6 months and 3
      months post-injury, in tetraplegia, paraplegia above T5 and that below T6
      respectively. The FIM scores in C6 patients were widely distributed from 56 to
      104. On the other hand, the ASIA motor score could subdivide C6 patients and
      related well to the FIM score. The mean FIM scores for each neurological level
      were similar to those previously reported, thus they appeared to be plateau
      scores. With regard to the motor score, we feel that it could reflect the
      disability of the patients better than considering the neurological levels alone.
      Also considering the changes in the physical FIM score over time within a year
      from the onset of the injury, there were differences in the ADL improvement
      patterns among patients with different neurological levels. It appears that
      timing of the highest physical FIM improvement for each neurological level can
      exist. Thus it is important not to delay the start of the rehabilitation of
      patients with spinal cord injury in proper time.

PMID- 8883188
TI  - Spinal deformity following surgery for spinal cord tumors and tumorous lesions:
      analysis based on an assessment of the spinal functional curve.
AB  - The mechanism of spinal deformity after surgical removal of a cervical spinal
      cord tumor or tumorous lesions was studied in 36 patients, based on the spinal
      functional curve prepared from the intersectional angle. The postoperative spinal
      deformity depends on the surgical level and the type of operation. In the
      laminectomy group, kyphosis of the upper cervical spine and compensatory
      increased lordosis of the lower cervical spine were observed in the C2
      laminectomy patients. Localized kyphosis of the spine at the cervicothoracic
      junction and compensatory increased lordosis of the upper cervical vertebrae were
      noted in the C7 laminectomy patients. In the laminoplasty group, spinal
      deformities were less frequently observed, and when present the deformity was
      limited to a slight increase of lordosis, even in patients who had the
      facetectomy. These facts demonstrate the preventive effect of the laminoplasty
      regarding postoperative spinal deformity. Laminoplasty with reconstruction of the
      erector spinal muscles and the nuchal ligament is recommended for patients with a
      spinal cord tumor or a tumorous lesion. The spinal functional curve was
      significant in studying the biomechanics of the vertebral column with the
      advantage that both alignment and mobility of the spine are simultaneously,
      respectively and precisely visualized.

PMID- 8883189
TI  - Strength post-spinal cord injury: myometer vs manual muscle test.
AB  - This study was designed to compare changes in strength after spinal cord injury
      (SCI) with the use of a hand held myometer to the manual muscle test (MMT).
      Eighty-eight C4-C8 Frankel A-D tetraplegic subjects were tested at various times
      up to 2 years post-SCI. Elbow flexor strength on successive examinations were
      grouped according to their early and later MMT scores (3.5 with no change in MMT.
      3.5 to 4.0, and 3.5 to 4.5; 4.0 with no change in MMT, 4.0 to 4.5, and 4.0 to
      5.0; 4.5 with no change in MMT, and 4.5 to 5.0). For each group, later myometric
      measurements (MYO) were expressed as percents of their earlier MYO and were
      analyzed using paired Student t-tests. Later MYO were 116, 205, 232% (P > 0.05, P
      < 0.002, P < 0.05) of their earlier MYO for groups 3.5 with no change in the MMT,
      3.5 to 4.0, and 3.5 to 4.5 respectively. Later MYO were 140, 139, 191% (P < 0.05,
      P < 0.02, P < 0.0001) of their earlier MYO for groups 4.0 with no change in MMT,
      4.0 to 4.5, and 4.0 to 5.0 respectively. Later MYO were 127 and 126% (P < 0.01, P
      < 0.02) of their earlier MYO for groups 4.5 with no change in MMT and 4.5 to 5.0
      respectively. In conclusion the hand held myometer detected changes in muscle
      strength not detected by the MMT.

PMID- 8883190
TI  - Epidemiology of spinal cord paralysis in Fiji: 1985-1994.
AB  - This descriptive analytical ten year (1985-1994) retrospective study assessed the
      pattern of spinal cord paralysis (SCP) in the Fiji Islands utilising medical
      rehabilitation hospital data. Fiji Islands is an archipelago of 300 islands in
      the south western Pacific with a multi-ethnic population of over three quarters
      of a million. Rehabilitation of all SCP is provided at the Medical Rehabilitation
      Unit (MRU). Data was collected from medical records of new SCP (n = 140) admitted
      to MRU and analysed with Epi Info 5 assessing associations between cause and
      other variables. The incidence of new SCP admitted to the MRU was
      18.7/million/year. There were 75 (53.6%) traumatic and 65 (46.4%) non-traumatic
      SCP. The incidence varied according to gender and ethnicity with Fijian male
      being at the highest (41.85) risk. Amongst traumatic SCP, 38.7% were due to
      falls, 25.3% motor vehicle accidents, 20% sports, 8% shallow water dive and 4%
      each deep sea diving and others, whereas among non-traumatic SCP, 52.3% were due
      to unknown causes, 32.3% infections, 9.2% neoplasms and 6.2% others. The
      male/female ratio was 4:1. The 16-30 year age group accounted for 35% of SCP. 31%
      had tetraplegia and 52.1% had complete lesions. The subset of the sample who
      experienced traumatic SCP were more likely to be employed, aged between 16-30
      years at the time of paralysis and to have complete tetraplegia. Those who
      experienced incomplete paraplegia were more likely to be unemployed, aged 46-60
      years and educated to primary level at the time of paralysis. There was a high
      proportion of complete spinal lesion when compared with other studies. The
      incidence of secondary complications such as pressure sores and UTI was also
      found to be high when compared with other studies. The results support the view
      that young Fijian males are most prone to sustaining traumatic spinal cord
      paralysis, and that there is a high incidence of secondary preventable
      complications. The need for preventative measures and adequate rehabilitation are
      emphasised.

PMID- 8883191
TI  - The inter rater reliability of the original and of the modified Ashworth scale
      for the assessment of spasticity in patients with spinal cord injury.
AB  - Thirty patients with spinal cord injury (SCI) were randomly selected to
      participate in this study which evaluated the inter rater reliability of the
      original and of the modified Ashworth scale for the assessment of spasticity in
      the lower limbs. A doctor and a physiotherapist rated the muscle tone of hip
      adductors, hip extensors, hip flexors and ankle plantarflexors according to the
      original and to the modified Ashworth scale. The results were analyzed using a
      Cohen's Kappa statistical test and showed varying levels of reliability for
      different muscle groups and limbs. Kappa values ranged between 0.21 and 0.61
      (mean 0.37). The original scale was slightly more reliable than was the modified
      scale. However, this difference was not significant (P > 0.05), and was not
      consistent between the two limbs and between different muscle groups. It was
      concluded that the Ashworth scale is of limited use in the assessment of
      spasticity in the lower limb of patients with SCI. Further work is required to
      establish a standardised speed of muscle stretching during the test, or to find
      more appropriate grades and descriptions of spasticity for this patient group.
      The effects of training of the raters in the use of the scales also warrants
      further investigation.

PMID- 8883192
TI  - Magnetic resonance imaging and biological changes in injured intervertebral discs
      under normal and increased mechanical demands.
AB  - STUDY DESIGN: An animal model was used to examine the short-term tissue response
      to changes in the mechanical environment after the structure (disc) is
      mechanically injured. OBJECTIVES: To observe changes in an injured intervertebral
      disc and the corresponding motion segment when the mechanical demands of the disc
      were increased by fusion of the adjacent motion segments. SUMMARY OF BACKGROUND
      DATA: Disc degeneration has been modeled in animals by producing a tear in the
      anulus via laminectomy, laparotomy, or posterolaterally. Methods of altering and
      quantifying the mechanics of the intervertebral joint by use of internal fixation
      and fusion in the canine have been developed. METHODS: Eight dogs divided into
      two groups (a study and a control group) had anular stab wounds (L2-L3). The
      study group was surgically instrumented posteriorly from L3 to L7. Magnetic
      resonance imaging studies were conducted for all animals before and periodically
      after the surgical procedures. At the end of the study, the segments were
      processed histologically and biochemically. RESULTS: Anular bulging was seen on
      magnetic resonance imaging in all control animals 4 months after injury and did
      not progress out until 6 months after injury. Similar changes were seen in study
      animals, but 75% were herniated by 6 months. Histologic changes correlated with
      magnetic resonance imaging changes. No significant difference in water or
      proteoglycan content of the disc tissue between groups was found. CONCLUSIONS:
      Progression from the bulging of the anulus to herniation was not evident in
      damaged discs not subjected to adjacent fusions. No change in water or
      proteoglycan content as a function of altered mechanical state was found,
      suggesting the short-term effect of the altered mechanics is on the mechanical
      structure and not on the cells or extracellular matrix.

PMID- 8883193
TI  - Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis. Functional and
      structural evaluation after local application on intraspinal nerve structures and
      blood vessels.
AB  - STUDY DESIGN: The effects on nerve tissue and blood vessels of locally applied
      chondroitinase ABC were studied in two experimental models using chymopapain and
      the vehicle of chondroitinase ABC for controls. OBJECTIVES: To assess the effects
      of chondroitinase ABC on blood vessels and nerve tissue after local application.
      SUMMARY OF BACKGROUND DATA: Chondroitinase ABC has been suggested for
      chemonucleolysis because it has a high specificity for nucleus pulposus matrix,
      which could mean a high efficiency in dissolving disc tissue combined with a low
      risk of side effects on other tissues. METHODS: Chondroitinase ABC or controls
      were injected intrathecally in the pig, and nerve conduction velocity and
      histologic changes were assessed after 7 days. The same substances were injected
      into the hamster cheek pouch and studied for 60 minutes for microvascular
      effects. The vehicle for the enzyme was used as a negative control and
      chymopapain in a therapeutic concentration served as a positive control. RESULTS:
      In all series there was a slight intrathecal fibrotic reaction that was most
      pronounced after chymopapain injection. The effects on nerve conduction velocity
      and nerve morphology were similar between chondroitinase ABC and its vehicle.
      Chymopapain induced a significant reduction in nerve conduction velocity and
      pronounced histologic changes. In the cheek pouch, chymopapain induced a stand
      still of blood flow at the injection site, and microhemorrhage and macromolecular
      leakage from the vessels at the border of the injection site. Only a slightly
      reduced blood flow was occasionally found after injection of chondroitinase ABC
      and controls. CONCLUSIONS: In agreement with the current literature, these
      observations indicate that chondroitinase ABC is safe regarding adverse effects
      on nerve tissue and blood vessels. The slight reduction in conduction velocity
      after intrathecal injection of chondroitinase ABC or its vehicle is most likely
      the result of surgical injury while releasing the nerve roots from the
      intrathecal fibrous adhesions. Such adhesions may be related to the laminectomy
      per se, and probably have no pathophysiologic significance.

PMID- 8883194
TI  - In situ rigidity of a new sliding rod for management of the growing spine in
      Duchenne muscular dystrophy.
AB  - STUDY DESIGN: This biomechanical, in vitro laboratory study determined the static
      stiffness of a new telescoping rod and the axial motion of this implant during
      various loading conditions. OBJECTIVES: To compare the stability of the new
      telescoping rod with the classic Luque instrumentation, and to determine whether
      the sliding rod elongates or contracts during spine motion. SUMMARY OF BACKGROUND
      DATA: A new telescoping rod was developed to stabilize the spine in children with
      Duchenne muscular dystrophy and to provide capacity for spinal growth. METHODS:
      The stability of 11 instrumented calf spines was determined in flexion,
      extension, lateral bending, and torsion to determine the stiffnesses of the
      spines instrumented with these two implants. The telescoping motion in the left
      and right rod was measured in the new rod system. RESULTS: In flexion, the spines
      with the telescoping rods were stiffer than those with the Luque implant.
      However, no significant differences in the stiffness coefficients were found for
      extension, lateral bending, or torsion. The restoring force of the telescoping
      system was greater than that of the Luque system in all directions. All modes of
      loading produced an accommodating change of length in the construct. CONCLUSIONS:
      The dynamic telescoping system provides stiffness comparable with that of
      established systems while allowing elongation during growth of the young patient.

PMID- 8883195
TI  - The role of imaging and in situ biomechanical testing in assessing pedicle screw
      pull-out strength.
AB  - STUDY DESIGN: This study determined the predictive ability of quantitative
      computed tomography, dual energy x-ray absorptiometry, pedicular geometry, and
      mechanical testing in assessing the strength of pedicle screw fixation in an in
      vitro mechanical test of intra-pedicular screw fixation in the human cadaveric
      lumbar spine. OBJECTIVE: To test several hypotheses regarding the relative
      predictive value of densitometry, pedicular geometry, and mechanical testing in
      describing pedicle screw pull-out. SUMMARY OF BACKGROUND DATA: Previous
      investigations have suggested that mechanical testing, geometry, and
      densitometry, determined by quantitative computed tomography or dual energy x-ray
      absorptiometry, predict the strength of the screw-bone system. However, no study
      has compared the relative predictive value of these techniques. METHODS: Forty
      nine pedicle screw cyclic-combined flexion-extension moment-axial pull-out tests
      were performed on human cadaveric lumbar vertebrae. The predictive ability of
      quantitative computed tomography, dual energy x-ray absorptiometry, insertional
      torque, in situ stiffness, and pedicular geometry was assessed using multiple
      regression. RESULTS: Several variables correlated to force at failure. However,
      multiple regression analysis showed that bone mineral density of the pedicle
      determined by quantitative computed tomography, insertional torque, and in situ
      stiffness when used in combination resulted in the strongest prediction of pull
      out force. No other measures provided additional predictive ability in the
      presence of these measures. CONCLUSIONS: Pedicle density determined by
      quantitative computed tomography when used with insertional torque and in situ
      stiffness provides the strongest predictive ability of screw pull-out. Geometric
      measures of the pedicle and density determined by dual energy x-ray
      absorptiometry do not provide additional predictive ability in the presence of
      these measures.

PMID- 8883196
TI  - Neck and shoulder pain after laminoplasty. A noticeable complication.
AB  - STUDY DESIGN: The authors retrospectively analyzed the prevalence and features of
      neck and shoulder pain (axial symptoms) after anterior interbody fusion and
      laminoplasty in patients with cervical spondylotic myelopathy. OBJECTIVES: To
      reveal the difference in prevalence of postoperative axial symptoms between
      anterior interbody fusion and laminoplasty and to clarify the pathogenesis of
      axial symptoms after laminoplasty. SUMMARY OF BACKGROUND DATA: Outcome of the
      cervical surgery is evaluated on neurologic status alone; axial symptoms after
      laminoplasty rarely have been investigated. Such symptoms, however, are often
      severe enough to interfere with a person's daily activity. METHODS: Ninety-eight
      patients had surgery for their disability secondary to cervical spondylotic
      myelopathy. Of those patients, 72 had laminoplasty, and 26 had anterior interbody
      fusion. The presence or absence of axial symptoms was investigated before and
      after surgery. The duration, severity, and laterality of symptoms were also
      recorded. RESULTS: The prevalence of postoperative axial symptoms was
      significantly higher after laminoplasty than after anterior fusion (60% vs. 19%;
      P < 0.05). In 18 patients (25%) from the laminoplasty group, the chief complaints
      after surgery were related to axial symptoms for more than 3 months, whereas in
      the anterior fusion group, no patient reported having such severe pain after
      surgery. CONCLUSIONS: The prevalence and severity of axial symptoms after
      laminoplasty proved to be higher and more serious than has been believed. Such
      symptoms should be considered in the evaluation of the outcome of cervical spinal
      surgery.

PMID- 8883197
TI  - Melatonin levels in idiopathic scoliosis. Diurnal and nocturnal serum melatonin
      levels in girls with adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Matched pairs of adolescent girls were used to compare serum
      melatonin levels in adolescent patients and control subjects with idiopathic
      scoliosis during the day and in the middle of the night. OBJECTIVES: To compare
      serum melatonin levels in patients with adolescent idiopathic scoliosis and
      matched control subjects during the day and in the middle of the night. SUMMARY
      OF BACKGROUND DATA: Recent studies using the chick as the animal model have
      suggested that the pineal gland and its main product, melatonin, might be
      involved in the cause of scoliosis. There have been no studies of melatonin
      levels in patients with adolescent idiopathic scoliosis. METHODS: Blood was
      collected from seven adolescent girls with idiopathic scoliosis and a group of
      seven age-matched control subjects. Two samples were collected, one in the middle
      of the day and one in the middle of the night, to examine the diurnal variation
      of melatonin production. Serum melatonin levels were measured using a
      radioimmunoassay technique. RESULTS: No significant differences were found in
      serum melatonin levels between experimental and control groups either during the
      day, when melatonin levels were low, or during the night, when melatonin levels
      were high. CONCLUSIONS: Whereas pinealectomy in young chickens leads to reduced
      melatonin levels and the development of scoliosis, the results of this study
      suggest that melatonin levels in mature patients who already have severe
      scoliosis do not differ from healthy subjects. Whether melatonin levels differ in
      humans between healthy subjects and patients with scoliosis at the time of onset
      of the disease remains to be seen.

PMID- 8883198
TI  - Long-term alterations of respiratory function in adolescents wearing a brace for
      idiopathic scoliosis.
AB  - STUDY DESIGN: This is a prospective study. OBJECTIVE: The authors investigated
      the effects of continuous bracing for idiopathic scoliosis on lung function
      variables at three consecutive time points over a 2-year period. SUMMARY OF
      BACKGROUND DATA: Only short-term results regarding lung function impairment
      caused by bracing exist. METHODS: Thirty adolescents (aged 13.6 +/- 1.8 years)
      with primary idiopathic thoracic scoliosis of 28.7 degrees +/- 4.1 degrees and
      primary lumbar scoliosis of 26.5 degrees +/- 10.4 degrees were treated with a
      Boston brace. All patients underwent pulmonary function studies at the beginning
      of brace treatment and 12 and 24 months after treatment initiation. The
      examinations were always performed while the patients were sitting, in and out of
      the brace. Patients removed the brace for 1 hour before the measurements for non
      brace-wearing were performed. Vital capacity, forced expiratory volume in 1.0
      second, and minute ventilation were determined with a low inertia, low resistance
      bell spirometer. Lung volume, including total lung capacity and functional
      residual capacity, was recorded. RESULTS: The primary thoracic scoliosis was
      corrected to 14.5 degrees +/- 4.0 degrees and the primary lumbar scoliosis to
      13.0 degrees +/- 6.0 degrees. The values of the following parameters taken while
      the brace was worn were significantly lower than those taken without the brace at
      all time points (one-way analysis of variance); vital capacity (P < 0.02), forced
      vital capacity (P < 0.03), functional residual capacity (P < 0.02), and residual
      volume (P < 0.05). Furthermore, the predicted negative residual volume and
      negative functional residual capacity values differed significantly in all time
      points from negative residual volume and negative functional residual capacity
      values of patients while wearing the Boston brace (P < 0.01 and P < 0.02,
      respectively). CONCLUSIONS: The results suggest that brace wearing for mild
      idiopathic scoliosis does not harm adolescent lung function over a 2-year period
      and is recommended for treatment of idiopathic scoliosis in early adolescence
      when the generally accepted criteria for bracing are fulfilled.

PMID- 8883199
TI  - Intraspinal cross-section areas measured on myelography--computed tomography. The
      relation to outcome in nonoperated lumbar disc herniation.
AB  - STUDY DESIGN: A prospective cohort study with computed tomographic-myelographic
      and clinical base registrations and follow-up by questionnaire 14 months after
      the onset of leg pain. OBJECTIVES: To detect predictive relations between
      intraspinal area measures and outcome in nonoperated lumbar disc herniation.
      SUMMARY OF BACKGROUND DATA: Myelography and computed tomography are qualitative
      methods ordinarily. The authors wanted to investigate the quantitative
      possibilities of computed tomographic technology in the pursuit of predictive
      measures. METHOD: Cross-section areas of the disc hernia, the dural sac, and the
      residual spinal canal were measured on computed tomography-myelography in 58
      patients with lumbar disc herniation who did not undergo surgery. Pain,
      disability, and vocational status were asked for in a questionnaire after 8
      months. RESULTS: After a median of 14 months from the onset of leg pain, 77% had
      returned to work, and only 7% were pain-free. The hernia size was not associated
      with the outcome measures. A high score for pain intensity and distal pain
      distribution was associated with a wide dural sac and a wide residual spinal
      canal. Disability and vocational status were not associated with any of the areas
      measured. Patients with the longest duration of leg pain had the narrowest spinal
      canals. CONCLUSIONS: Area measurements on computed tomography-myelography could
      not predict outcome in patients with lumbar disc herniation who were not operated
      on. There was an association between pain and a wide dural sac, which might
      underscore the sensory role of dura in protracted cases of sciatica.

PMID- 8883200
TI  - Detection of Mycobacterium tuberculosis in formaldehyde solution-fixed, paraffin
      embedded tissue by polymerase chain reaction in Pott's disease.
AB  - STUDY DESIGN: Twenty-five formaldehyde solution-fixed, paraffin-embedded tissue
      blocks from vertebral biopsy specimen materials with presumptive diagnosis of
      tuberculous spondylitis and nonspecific vertebral osteomyelitis were studied.
      OBJECTIVES: To evaluate the sensitivity and specificity of polymerase chain
      reaction in detecting Mycobacterium tuberculosis in formaldehyde solution-fixed,
      paraffin-embedded tissue samples from histologically proved tuberculous
      spondylitis. SUMMARY OF BACKGROUND DATA: Diagnosis of a mycobacterial infection
      is a long and tedious process; because of the slow growth rate of mycobacteria on
      solid media, identification and antibiotic sensitivity testing can take up to 10
      weeks, but the sensitivity of culture can be as low as 50%. Direct microscopy is
      insensitive because clinical samples may contain only few organisms. Recently,
      polymerase chain reaction has been applied in the rapid amplification and
      identification of many organisms, including mycobacteria. METHODS: The DNAs were
      extracted from 25 paraffin-embedded tissue blocks. An insertion element IS 6110
      (Integrated DNA Tec. Inc., Corrallville, IA), a DNA sequence unique to
      Mycobacterium complex (M. tuberculosis and the subspecies Mycobacterium bovis),
      was amplified by polymerase chain reaction. Polymerase chain reaction results
      were compared with those of Mycobacterium culture, acid-fast bacilli staining,
      and histologic findings. RESULTS: Polymerase chain reaction was positive in 18
      cases of 19 tuberculous spondylitis. Three of the polymerase chain reaction test
      results were positive with concomitant negative culture and positive acid-fast
      bacilli staining. There were six chronic nonspecific infections, and polymerase
      chain reaction results were negative in five cases; in the single positive case,
      DNA amplification results remained positive even after three repeated tests.
      CONCLUSION: Polymerase chain reaction has a sensitivity of 94.7%, specificity of
      83.3%, positive predictive value of 94.7%, and a negative predictive value of
      83.3%. Accuracy was calculated as 92%.

PMID- 8883201
TI  - Comparison of preoperative selective spinal angiography and somatosensory-evoked
      potential monitoring with temporary occlusion of segmental vessels during
      anterior spinal surgery.
AB  - STUDY DESIGN: The results of preoperative selective spinal angiography were
      compared with intraoperative occlusion of segmental arteries and somatosensory
      evoked potential monitoring during anterior spinal surgery. OBJECTIVES: To
      determine if temporary occlusion of major radicular vessels supplying the spinal
      cord would result in intraoperative somatosensory-evoked potential changes.
      SUMMARY OF BACKGROUND DATA: Temporary occlusion of segmental spinal arteries with
      concomitant somato-sensory-evoked potential monitoring has been used during
      anterior spinal surgery to avoid intraoperative vascular paraplegias caused by
      permanent ligations of vessels critical to the blood supply of the spinal cord.
      METHODS: Preoperative selective spinal angiography was performed in 16 patients
      to identify important radicular arteries supplying the spinal cord. At the time
      of anterior spinal surgery, temporary occlusion of segmental vessels was
      accomplished with somatosensory-evoked potential monitoring. RESULTS: Thirty-two
      radicular arteries were identified by arteriography in 16 patients. Temporary
      occlusion of nine segmental arteries in the surgical field supplying these
      radicular vessels resulted in no somatosensory-evoked potential changes.
      CONCLUSIONS: The lack of somatosensory-evoked potential changes after temporary
      occlusion of segmental arteries from which radicular arteries supply the spinal
      cord demonstrates sufficient perimedullary collateral circulation in that area of
      the spinal cord.

PMID- 8883202
TI  - Relationship of lumbar strength in shipyard workers to workplace injury claims.
AB  - STUDY DESIGN: Strength testing of lumbar extensors of shipyard workers without
      back injury claims was accomplished to compare isolated lumbar strength with the
      severity of their workplace physical demands and the incidence of workplace back
      injury during a 2-year period. OBJECTIVES: To determine if strength is a
      predictor of workplace injury and if there is a relationship between the physical
      demands of the job and strength. SUMMARY OF BACKGROUND DATA: The role of
      preplacement strength testing has not been clarified as a potential means for
      predicting workplace injury. It has not been clarified whether work activity
      affects the strength of the worker. METHODS: One hundred fifty-two shipyard
      workers were strength tested for isometric lumbar extensor strength. They had
      been classified as to the severity of their job demands according to the Physical
      Demand Characteristics. All workers at this industry were likewise classified.
      Those workers who were tested were followed for 2 years to evaluate for claims of
      back injury. RESULTS: There was a higher incidence of low back injuries in the
      heavy and very heavy classification. There was, however, no difference in
      strength among those workers classified in medium, heavy, and very heavy work.
      Nine percent of those workers tested had back pains during the following 2 years.
      All but two had higher-than-average strength. CONCLUSIONS: There is no evidence
      that preplacement back strength testing would predict workplace claims of injury.

PMID- 8883204
TI  - Chronic osteomyelitis of the spine managed with a free flap of latissimus dorsi.
      A case report.
AB  - STUDY DESIGN: A patient with intractable spinal osteomyelitis who underwent
      surgery 12 times with persistent exposed bone is presented. OBJECTIVES: To
      demonstrate the effectiveness of free-flap grafting for managing difficult spinal
      osteomyelitis wounds. SUMMARY OF BACKGROUND DATA: Conventional procedures can
      usually achieve wound closure, but they may not work for advanced cases. METHODS:
      A free latissimus dorsi flap was transferred for reconstruction. The muscle
      component was used to obliterate the dead space and cover the exposed bone, and
      the skin component was used for tension-free closure of the wound. RESULTS: The
      wound healed dramatically. There was no recurrence of infection at 2-year follow
      up evaluation. CONCLUSIONS: For an intractable spinal osteomyelitis wound, a free
      flap should be considered, although the surgery is difficult. Technical
      precautions in performing this operation are given.

PMID- 8883203
TI  - The BWM spinal fixator system. A preliminary report of a 2-year prospective,
      international multicenter study in a range of indications requiring surgical
      intervention for bone grafting and pedicle screw fixation.
AB  - STUDY DESIGN: A prospective, international, multicenter study of 400 patients who
      received the BWM fixator system. OBJECTIVES: To assess the effectiveness and
      safety of the system in the management of various conditions requiring spinal
      fixation and bone grafting. SUMMARY OF BACKGROUND DATA: The BWM system was
      developed for the management of spinal instability of all etiologies occurring in
      the thoracic, thoracolumbar, and lumbosacral spine. METHODS: Patients with
      fracture, tumor, spondylolisthesis, spondylitis, failed back, or other
      degenerative conditions of the spine received the BWM instrumentation as
      described in the study literature and were regularly reviewed for 2 years.
      RESULTS: The results from the first 200 patients to complete the study showed an
      overall graft fusion rate of 94% (95% confidence interval: 91.3%-97.6%). There
      were marked improvements in measures of functional ability (P < 0.001, Wilcoxon
      test). Before surgery, less than half the patients were capable of outdoor
      activity. At 2 years, 80% were able to undertake outdoor activity. There were few
      perioperative difficulties reported. Postoperative complications associated with
      major surgery were seen in 18% patients. There were 23 (2.6%) pedicle screw
      failures, including two loosenings, and 13 (2.5%) spacer element failures,
      including three loosenings. CONCLUSIONS: Clinical failure was not necessarily a
      consequence of component failure. The BWM fixator provided excellent
      stabilization during the process of bone graft consolidation. The risks of
      complication or component failure were no higher than those associated with
      similar devices.

PMID- 8883205
TI  - Ganglion cyst of the odontoid process. Case report and review of the literature.
AB  - STUDY DESIGN: This case report illustrates that although it is rare, a ganglion
      cyst can occur intraosseously in the odontoid process. OBJECTIVES: The tissue
      diagnosis was established by surgical resection of the cyst membrane and
      evacuation of the cyst content. The patient tolerated the procedure well, and the
      hospital course was uneventful. SUMMARY OF BACKGROUND DATA: Synovial cyst of the
      spine is uncommon and is usually found in the lumbar region. Its occurrence in
      the cervical spine is rare, and no cases in the odontoid process, to the authors'
      knowledge, have been reported. METHODS: This patient was evaluated initially for
      neck pain, which led to radiographic studies depicting the lesion. It raised the
      suspicion of metastatic neoplastic process, although the search for primary
      source proved to be negative. A biopsy was indicated. RESULTS: Surgical findings
      consisted of mucoid material field cavity lined by a thin membrane. The cyst was
      excised, and pathologic evaluation confirmed the diagnosis of synovial cyst.
      CONCLUSION: The correct radiographic diagnosis of this patient was not made
      because of lack of experience with such lesions in this location. The authors
      hope that this case report helps raise the awareness of clinicians in considering
      this diagnosis when facing similar radiographic presentation.

PMID- 8883206
TI  - Cervical kyphosis after resolution of myopathic head drop. A case report.
AB  - STUDY DESIGN: This is a case report. OBJECTIVES: To present a case of cervical
      kyphosis after resolution of myopathic head drop. SUMMARY OF BACKGROUND DATA:
      Myopathic head drop is a severe and persistent local myopathy that never
      progresses beyond the neck extensor muscles. METHODS: A case is reported of a
      hospitalized psychiatric patient who experienced the sudden onset of severe neck
      extensor weakness consistent with myopathic head drop. RESULTS: Although
      myopathic head drop resolved after 2 years, it left a disabling residual skeletal
      deformity of the cervical spine. CONCLUSIONS: Myopathic head drop may be a cause
      of cervical kyphosis.

PMID- 8883207
TI  - Computer-aided pedicle screw placement using frameless stereotaxis.
AB  - STUDY DESIGN: In vitro assessment of accuracy and reliability of frameless
      stereotaxis for insertion of pedicle screws in human cadaveric lumbar spine.
      OBJECTIVES: To assess a new method of targeting and placing pedicle screws in a
      human cadaver study. SUMMARY OF BACKGROUND DATA: Pedicle screw instrumentation is
      common. Complications may occur from improper placement of screws. Even when
      performed by experienced spinal surgeons, improper placement can occur in 5.2% of
      pedicles instrumented. Development of computer-guided methods of pedicle screw
      insertion may decrease this complication rate. METHODS: The technique used
      preoperative computed tomography scans together with a commercial neurosurgical
      navigational computer system to assist in placing guidewires in the pedicles. A
      section of human cadaver spine was first scanned and the data transferred to the
      workstation. The image data set and physical specimen were then registered by
      using an instrumented articulated arm to identify selected points on the specimen
      and randomly sample surface points. Eight highly repeatable locations on each
      vertebral body were found to be suitable for registration, but better overall
      accuracy was obtained when surface matching was used in combination with these
      points. Under guidance of image on the computer, Kirschner wires were inserted
      into the pedicles of four vertebral bodies. The spine was rescanned, and the
      planned and resulting positions of the wires compared. RESULTS: The average
      distance between the planned and resulting wire entry point was 1.2 mm, with an
      average difference in planned and resulting trajectories of 6.0 degrees.
      CONCLUSIONS: Computer-aided pedicle screw instrumentation is feasible. Further
      technical points require clarification before widespread use is possible.

PMID- 8883208
TI  - Percutaneous transpedicular biopsy of vertebral body lesions.
AB  - STUDY DESIGN: This prospective study evaluates the use of transpedicular biopsy
      in obtaining diagnostic tissue from vertebral body lesions. OBJECTIVE: To report
      the authors' experience of all (N = 32) percutaneous transpedicular biopsies
      performed between 1990-1994. SUMMARY OF BACKGROUND DATA: Previous articles have
      discussed the value of open biopsy of the vertebral body using a Craig needle. A
      large series of closed percutaneous transpedicular biopsies have not been
      reported. METHODS: The authors evaluated 32 patients (26 outpatients, six
      inpatients) who underwent transpedicular biopsy for T1-L4 lesions of the
      vertebral bodies. None of the tumors had an extraosseous component. Biopsy
      specimens were obtained from 25 lesions using C-arm fluoroscopy; seven were
      guided by computed tomography. All biopsies were performed with a 14- to 17-gauge
      bone biopsy needle. RESULTS: The needle passed through the pedicle into the site
      of disease in all patients, as confirmed by C-arm fluoroscopy or computed
      tomography. There were 22 malignancies; four isolated compression fractures, two
      at T6, one at T7, one at T8; four cases of infection or inflammation; and one
      case each of Paget's disease and myelofibrosis. Two patients required a second
      biopsy because the tissue sample was suspicious for lymphoma but not diagnostic.
      All 26 outpatients were discharged after a 2-hour observation period. There were
      no complications. CONCLUSION: Transpedicular biopsy of deep vertebral body
      lesions using a bone biopsy needle under computed tomography or fluoroscopy
      guidance can be performed safely and efficaciously as an outpatient procedure.

PMID- 8883209
TI  - Repair of defects in spondylolysis by segmental pedicular screw hook fixation. A
      preliminary report.
AB  - STUDY DESIGN: Clinical testing of segmental pedicular screw hook fixation
      repairing defects in lumbar spondylolysis. OBJECTIVES: The authors tested
      segmental pedicular screw hook fixation using ISOLA implants (AcroMed Corp.,
      Cleveland, OH) to maintain direct repair of the defect in pars interarticularis
      while fusion occurs. The device should not break while fusion takes place with
      out a postoperative body cast. SUMMARY OF BACKGROUND DATA: Previous techniques of
      direct repair of defects in lumbar spondylolysis have not been successful
      universally, and wire breakage has occurred despite the use of a postoperative
      body cast. METHODS: This technique stabilizes bone grafted to the detect by a
      pedicular screw, a hook, and a rod used in combination. Six patients with lumbar
      spondylolysis were treated by means of this technique. RESULTS: Postoperatively,
      all patients with low back pain or radicular pain experienced significant relief.
      Radiographs, including lateral flexion-extension radiographs and tomograms,
      showed five patients to have a bilateral union and one a unilateral union, and
      none of the instrumentation failed. CONCLUSION: This technique is considered
      useful for direct repair of the defects found in lumbar spondylolysis.

PMID- 8883210
TI  - Spinal stenosis and neurogenic claudication.
AB  - Neurogenic claudication is diagnosed from a classical history and complementary
      spinal imaging. The abnormal signs may be few. It should be distinguished from
      intermittent claudication (peripheral vascular disease), referred pain from the
      back or root pain that is aggravated by walking, and psychological distress.
      Pathologically, a developmentally small canal is usually affected by multiple
      levels of segmental degenerative change, with venous pooling in the cauda equina
      between two levels of low pressure stenosis. There is probably then a failure of
      arterial vasodilatation of the congested roots in response to exercise, with
      symptoms in the legs when walking. Once established, symptoms tend neither to
      improve nor deteriorate. Conservative management is reasonable. Otherwise
      decompression at the most significant stenotic level is probably adequate to
      obtain a good surgical result.

PMID- 8883211
TI  - Trends in ski and snowboard injuries.

PMID- 8883212
TI  - Evaluation of body composition. Current issues.
AB  - In the selection of body composition field methods and prediction equations,
      exercise and health practitioners must consider their clients' demographics.
      Factors, such as age, gender, level of adiposity, physical activity and ethnicity
      influence the choice of method and equation. Also, it is important to evaluate
      the relative worth of prediction equations in terms of the criterion method used
      to derive reference measures of body composition for equation development. Given
      that hydrodensitometry, hydrometry and dual-energy x-ray absorptiometry are
      subject to measurement error and violation of basic assumptions underlying their
      use, none of these should be considered as a 'gold standard' method for in vivo
      body composition assessment. Reference methods, based on whole-body, 2-component
      body composition models, are limited, particularly for individuals whose fat-free
      body (FFB) density and hydration differ from values assumed for 2-component
      models. Use of field method prediction equations developed from 2-component model
      (Siri equation) reference measures of body composition will systematically
      underestimate relative body fatness of American Indian women, Black men and
      women, and Hispanic women because the average FFB density of these ethnic groups
      exceeds the assumed value (1.1 g/ml). Thus, some researchers have developed
      prediction equations based on multicomponent model estimates of body composition
      that take into account interindividual variability in the water, mineral, and
      protein content of the FFB. One multicomponent model approach adjusts body
      density (measured via hydrodensitometry) for total body water (measured by
      hydrometry) and/or total body mineral estimated from bone mineral (measured via
      dual-energy x-ray absorptiometry). Skinfold (SKF), bioelectrical impedance
      analysis (BIA), and near-infrared interactance (NIR) are 3 body composition
      methods used in clinical settings. Unfortunately, the overwhelming majority of
      field method prediction equations have been developed and cross-validated for
      White populations and are based on 2-component model reference measures. Because
      ethnicity may affect the composition of the FFB and regional fat distribution,
      race-specific prediction equations may need to be developed for some ethnic
      groups. To date, race-specific SKF (American Indian women, Black men, and Asian
      adults), BIA (American Indian women and Asian adults), and NIR (American Indian
      women and White women) equations have been developed. However, these equations
      need to be cross-validated on additional samples from these ethnic groups. In
      summary, research strongly suggests that multicomponent models need to be used in
      order to quantify differences in FFB composition due to ethnicity so that
      accurate SKF, BIA, and NIR prediction equations can be developed. Assessment of
      body composition in vivo may be enhanced by using advanced technologies such as
      dual-energy x-ray absorptiometry and hydrometry to refine hydrodensitometry.
      Practitioners should carefully select and use only those prediction equations
      that have been developed and cross-validated for specific ethnic groups.
      Additional research is needed to test the accuracy and applicability of
      previously published prediction equations for the American Indian, Asian, Black,
      and Hispanic populations.

PMID- 8883214
TI  - The effectiveness of resistance training in children. A meta-analysis.
AB  - Many recent studies have reported that resistance training can be effective in
      producing strength gains among prepubescents. These studies appear to refute the
      early claims of ineffectiveness of resistance training in children. A meta
      analysis procedure combines the results of individual empirical studies and
      estimates a standardised effect, termed effect size. This effect size is based on
      the scores of the control and experimental groups before and after training. It
      defines the difference between the gain of the experimental and control groups,
      divided by the standard deviation of the pooled variances of both groups. A
      literature search revealed 28 studies which described a resistance training
      programme for girls and boys under the age of 12 and 13 years, respectively.
      Presumably, these children were pre- or early-pubescents. However, only 9 of
      these studies provided the necessary data to calculate the effect size and could
      be included in the analysis. The majority of the studies showed a gain in
      strength between 13 and 30%. The overall mean effect size was found to be 0.57.
      This signifies that following training, the average child in the resistance
      training group was above 71.6% of the children in the control group. The
      effectiveness of resistance training can be influenced by factors such as age and
      maturation, gender, as well as the frequency, duration and intensity of the
      training programme. The studies included in the analysis examined participants of
      varying ages and did not demonstrate a clear influence of age. Most studies
      examined only boys or a mixed group of boys and girls. Therefore, the influence
      of gender on the effectiveness of resistance training in prepubescents cannot yet
      be determined. Nevertheless, in the few studies where boys and girls were
      examined separately, no difference was found in the effect of resistance training
      between genders. It appears that a training frequency of twice per week is
      sufficient to induce strength gains in children. However, the minimal, or for
      that matter optimal, duration and intensity are not clear. Some of the weaknesses
      observed in the reviewed studies include: (i) the lack of control for a possible
      learning effect; (ii) non-randomisation into the training and control groups;
      (iii) no report of adherence rate; (iv) a reliance on boys as study participants;
      and (v) too little information on the type, volume and intensity of training.
      Future studies should take these weaknesses into consideration.

PMID- 8883213
TI  - Use of blood lactate measurements for prediction of exercise performance and for
      control of training. Recommendations for long-distance running.
AB  - Time over a distance, i.e. speed, is the reference for performance for all events
      whose rules are based on locomotion in different mechanical constraints. A
      certain power output has to be maintained during a distance or over time. The
      energy requirements and metabolic support for optimal performance are functions
      of the length of the race and the intensity at which it is completed. However,
      despite the complexity of the regulation of lactate metabolism, blood lactate
      measurements can be used by coaches for prediction of exercise performance. The
      anaerobic threshold, commonly defined as the exercise intensity, speed or
      fraction of maximal oxygen uptake (VO2max) at a fixed blood lactate level or at a
      maximal lactate steady-state (MLSS), has been accepted as a measure of the
      endurance. The blood lactate threshold, expressed as a fraction of the velocity
      associated with VO2max, depends on the relationship between velocity and oxygen
      uptake (VO2). The measurement of the post-competition blood lactate in short
      events (lasting 1 to 2 minutes) has been found to be related to the performance
      in events (400 to 800m in running). Blood lactate levels can be used to assist
      with determining training exercise intensity. However, to interpret the training
      effect on the blood lactate profile, the athlete's nutritional state and exercise
      protocol have also to be controlled. Moreover, improvement of fractional
      utilisation of VO2max at the MLSS has to be considered among all discriminating
      factors of the performance, such as the velocity associated with VO2max.

PMID- 8883215
TI  - Preventing equestrian injuries. Locking the stable door.
AB  - The medical and sports literature databases were searched for equestrian sports
      related injury published in English since 1980, together with conference
      abstracts and discussions with equestrian sporting bodies. This literature was
      critically reviewed, with emphasis on measures to prevent or control injury i.e.
      countermeasures. While there is considerable literature available on the
      epidemiology of injury incurred in most equestrian sports, there is little on the
      prevention of these injuries. Case-control or other studies evaluating the
      effectiveness of the countermeasures suggested by authors do not seem to exist.
      There is a good body of epidemiology that supports the proper use of approved
      helmets as a means of preventing injury in these sports. However, protective
      helmets do not always prevent injury as expected, and many riders do not choose
      to wear them because of perceived poor design. The search for the ideal
      equestrian helmet should continue. Ideally the effectiveness of helmets should be
      assessed scientifically. Among the other countermeasures discussed are the use of
      rules and regulations for conduct of events, knowledge of horse behaviour, well
      conducted lessons, contraindicated medical conditions, public education, rider
      education, appropriate equipment and clothing, the riding environment, rider
      experience, safety stirrups, body protectors, falling techniques, and first aid
      measures. Even though the injury rate for equestrians is relatively low when
      compared with other sports, the injuries that are incurred are usually severe.
      prevention is often difficult because the behaviour of the horse is
      unpredictable. Countermeasures used for prevention should be evaluated for the
      effectiveness to reduce the frequency and severity of injuries to equestrians.

PMID- 8883216
TI  - Stress fractures. Current concepts of diagnosis and treatment.
AB  - The stress fracture is a common injury seen by healthcare professionals caring
      for athletes. They have been described in numerous areas of the skeletal system
      and in multiple sports. However, they are most commonly seen in the lower
      extremities, with running the reported cause in most cases. Stress fractures
      result from repetitive, cyclic loading of bone which overwhelms the reparative
      ability of the skeletal system. Mechanically, three events may lead to stress
      fractures. First, the applied load can be increased. Secondly, the number of
      applied stresses can increase. Finally, the surface area over which the load is
      applied can be decreased. Diagnosis requires thorough clinical evaluation with a
      high index of suspicion for stress fractures. History must focus on examining the
      athletes training regimen, especially any changes in distance, running surface
      and type of shoe. Physical examination varies depending on the location of the
      stress fracture. Ultrasound is a possible adjunct to the physical examination.
      Initial plain radiological evaluation may be normal, especially early in the
      course of a stress fracture. Further radiological evaluation may be necessary to
      make a definitive diagnosis. Repeating plain radiographs, bone scintigraphy,
      magnetic resonance imaging and computerised tomography are all possible options.
      Treatment options begin with rest and cessation of the precipitating activity.
      This should be 'active rest' in which the athlete continues to exercise depending
      on the site of the fracture. The athlete should be evaluated from a biomechanical
      point of view and any abnormalities dealt with prior to rehabilitation. Possible
      adjuncts to treatment include pneumatic braces and electromagnetic field therapy.
      There are specific stress fractures that must be considered at-risk for
      complications of healing. The treatment of these fractures begins with
      immobilisation and may require surgery pending response to therapy. Stress
      fractures occur more frequently in female athletes in relation to their male
      counterparts. There is a demonstrated relationship to eating disorders,
      amenorrhea and osteoporosis, or the female athlete triad. Thus, stress fractures
      in the female athlete requires additional investigation into those areas. The
      diagnosis and treatment of stress fractures is a challenge for the physician
      caring for the athlete. It requires a high index of suspicion combined with a
      strong knowledge of the at-risk stress fractures and their complications.
      Accurate and timely diagnosis is required to prevent possible costly and
      disabling complications.

PMID- 8883217
TI  - Mammalian 3 alpha-hydroxysteroid dehydrogenases.
AB  - Mammalian 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSDs) regulate steroid
      hormone levels. For example, hepatic 3 alpha-HSDs inactivate circulating
      androgens, progestins, and glucocorticoids. In target tissues they regulate
      access of steroid hormones to steroid hormone receptors. For example, in the
      prostate 3 alpha-HSD acts as a molecular switch and controls the amount of 5
      alpha-dihydrotestosterone that can bind to the androgen receptor, while in the
      brain 3 alpha-HSD can regulate the amount of tetrahydrosteroids that can alter
      GABAa receptor function. Molecular cloning indicates that these mammalian 3 alpha
      HSDs belong to the aldo-keto reductase superfamily and that they are highly
      homologous proteins. Using the three-dimensional structure of rat liver 3 alpha
      HSD as a template for site-directed mutagenesis, details regarding structure
      function relationships, including catalysis and cofactor and steroid hormone
      recognition have been elucidated. These details may be relevant to all mammalian
      3 alpha-HSDs.

PMID- 8883218
TI  - Structural studies of loteprednol etabonate and other analogs of prednisolone
      using NMR techniques.
AB  - Several structural analogs of prednisolone, prepared by esterification of the
      carboxylic and/or the C(17)-hydroxy group of 11 beta, 17 alpha-dihydroxy-3-oxo
      androsta-1,4-diene-17 beta-carboxylic acid, were investigated by NMR. Step-by
      step analysis of the 1H and 13C NMR spectra of these steroids, including proton
      proton selective decoupling, nuclear Overhauser effect difference spectra,
      attached proton test, proton-carbon correlation (HETCOR), proton-proton
      correlation (COSY), and long-range proton-carbon decoupling (INAPT) techniques,
      led to unequivocal assignments of all their proton and carbon resonances. The
      stereochemical structure of loteprednol etabonate (chloromethyl 17 alpha
      ethoxycarbonyloxy-11 beta-hydroxy-3-oxoandrosta-1,4-diene-17 beta-carboxylate,
      1), a soft corticosteroid antiinflammatory drug, was proved to be analogous to
      prednisolone.

PMID- 8883220
TI  - New synthetic strategy for the synthesis of 24-epibrassinolide.
AB  - The synthesis of (22E,24R)-5 alpha-ergosta-2,22-dien-6-one (2), a key
      intermediate to the preparation of 24-epibrassinolide (1), was achieved through
      the 3,6-diketone 8 in a 40% overall yield in five steps starting from ergosterol
      (3).

PMID- 8883219
TI  - Androgenic up-regulation of androgen receptor cDNA expression in androgen
      independent prostate cancer cells.
AB  - The expression of the androgen receptor (AR) gene is regulated by androgens.
      Although androgens down-regulate AR mRNA in most cell lines and tissues,
      including the prostate, up-regulation occurs in some tissues. Androgen-mediated
      reduction in AR mRNA is reproduced in COS1 cells and in the androgen-sensitive
      human prostate cancer cell line LNCaP when each expresses the AR cDNA. We have
      previously established that the AR cDNA contains the requisite sequences for this
      down-regulation. Here we shown that androgen promoted up-regulation of AR mRNA in
      two androgen-independent human prostate cancer cell lines, PC3 and DU145, when
      each was transfected with a human AR cDNA. This effect was due to the AR cDNA and
      not to the heterologous promoter driving AR expression. In addition to up
      regulation of AR mRNA, androgen induced comparable increases in AR protein levels
      in PC3 cells stably expressing an AR cDNA (PC3/AR). Up-regulation of AR in PC3/AR
      cells was accompanied by failure of these cells to undergo desensitization or
      inactivation of AR following prolonged (96 h) androgen administration, whereas
      the same conditions resulted in desensitization of AR transactivation in LNCaP
      cells and in CVl cells that stably express the AR cDNA. Androgen treatment of
      PC3/AR cells resulted in induction of an androgen-regulated reporter gene (MMTV
      CAT) as well as the native prostate-specific antigen gene, which is silent in
      untransfected PC3 but is androgen up-regulated in LNCaP and in the prostate.
      These results suggest that ectopic expression of AR in androgen-independent
      prostate cancer cell lines establishes both typical and atypical androgenic
      responses in a target gene-specific manner. Androgenic up-regulation of AR cDNA
      expression may be due to distinct signaling mechanisms that influence androgen
      action in androgen-independent prostate cancer cells.

PMID- 8883222
TI  - Binding of site-directed monoclonal antibodies to an epitope located in the A/B
      region (amino acids 140-154) of human estrogen receptor-induced conformational
      changes in an epitope in the DNA-binding domain.
AB  - The interactions of estrogen receptor (ER) with monoclonal antibody (Mab) F9,
      developed against a synthetic 30-mer hybrid oligopeptide, were determined in the
      presence or absence of Mab NMT-1, raised against 15-mer peptide from the N
      terminal A/B region (amino acids 140- 154) or Mab 213, raised to a peptide AT3 in
      the DNA-binding domain (amino acids 247-263). Mab F9 bound ER and formed a
      complex sedimenting at the approximately 11S region of the gradients. Mabs 213
      and NMT-1 bound ER and formed complexes sedimenting at approximately 7S and 9S,
      respectively. Preincubation of ER with Mab 213, followed by reincubation with Mab
      F9, resulted in a complex sedimenting at the approximately 11S region of the
      gradients. Similarly, preincubation of ER with Mab NMT-1 followed by reincubation
      with Mab F9 also produced an approximately 11S complex on the gradients. These
      observations suggest that binding of Mab F9 to ER induced conformational changes
      causing the release of Mab 213 and Mab NMT-1 from ER. Furthermore, binding of Mab
      NMT-1 to the A/B region of ER also produced conformational changes causing the
      release of Mab 213 from its epitope in the DNA-binding region. These results
      indicate that binding of Mab F9 and Mab NMT-1, with epitopes located within amino
      acids 140-154 of the A/B region of ER, induced conformational changes in the DNA
      binding domain, as determined by the inability of Mab 213 to remain bound to its
      epitope. These data further suggest that the DNA-binding region is sensitive to
      conformational changes induced in the native protein.

PMID- 8883221
TI  - Effect of YM 9429, a potent teratogen, on cholesterol biosynthesis in cultured
      cells and rat liver microsomes.
AB  - YM 9429 (cis-1-[4-(p-menthan-8-yloxy)phenyl]piperidine) is a hypolipidemic agent
      with a potent and specific teratogenicity, inducing cleft palate and skeletal
      variations in rats. Since cleft palate is generally observed in the Smith-Lemli
      Opitz syndrome, a common syndrome of multiple congenital anomalies caused by
      reduced activity of 7-dehydrocholesterol delta 7-reductase (3 beta-hydroxysteroid
      delta 7-reductase), the final enzyme in the cholesterol biosynthetic pathway, YM
      9429 was suspected of being an inhibitor of this enzyme. To prove this
      hypothesis, YM 9429 was added to cultured human skin fibroblasts and to cultured
      Morris hepatoma cells and incubated with [5-3H]mevalonolactone. After 24 h,
      radiolabeled 7-dehydrocholesterol accumulated in the cells, whereas the formation
      of radiolabeled cholesterol was markedly reduced. The results indicate that YM
      9429 inhibits the conversion of 7-dehydrocholesterol to cholesterol catalyzed by
      the microsomal enzyme 7-dehydrocholesterol delta 7-reductase. In rat liver
      microsomes, the mode of inhibition was found to be noncompetitive, with a Ki of
      40 microM. These results suggest that YM 9429 induced developmental abnormalities
      in rats by the same mechanism as the Smith-Lemli-Opitz syndrome. This compound
      might be useful for studying the pathogenesis of anomalies in animal models of
      the Smith-Lemli-Opitz syndrome.

PMID- 8883223
TI  - Spectroscopic investigations of dehydroepiandrosterone. Part II: Photoelectron
      spectrum and electronic structure.
AB  - The gas phase electronic structure of dehydroepiandrosterone (3 beta-hydroxy-5
      alpha-androstene-17-one, DHEA) is elucidated from its Het photoelectron spectrum,
      quantum chemical calculations, and correlation with spectra of the related
      molecules 5 alpha-androstene-17-one (I) and epiandrosterone (3 beta-hydroxy-5
      alpha-androstane-17-one) (2). The lowest ionization energy event in DHEA is shown
      to correspond to a pi-ionization energy of approximately 8.5 eV, followed closely
      and overlapped in part by the carbonyl lone pair ionization at 8.7 eV.

PMID- 8883224
TI  - Delirium: is the confusion slowly clearing up.

PMID- 8883225
TI  - The Cleveland Clinic Foundation Harry R. Horvitz Palliative Care Center.
AB  - In 1994, the Harry R. Horvitz Palliative Care Center opened as a dedicated
      inpatient palliative care unit within a comprehensive Palliative Care Program in
      the United States. The program is designated by the World Health Organization as
      a national and international demonstration project in the provision of palliative
      care. The mission of the program and the inpatient unit is to provide excellent
      care for patients with advanced cancer and their families throughout the illness
      and during bereavement. The need for the 23-bed inpatient unit was documented by
      the increasing number of cancer deaths each year and the complex physical and
      psychosocial problems patients and families experience throughout the course of
      their illness. Health care professionals specially trained in palliative care are
      an essential component of a dedicated program within a cancer center.

PMID- 8883226
TI  - Physicians and death: comments and behaviour of 605 doctors in the north-east of
      Italy.
AB  - The aim of this study was to determine the influence of socio-demographic and
      professional factors on physicians' attitudes to the terminally ill. Between May
      1992 and May 1993, a survey was conducted in the province of Pordenone (north
      east, Italy) in order to analyse a number of specific issues, such as emotional
      involvement, the need for aggressive treatments and the communication of
      diagnosis and prognosis. After obtaining a list of board-certified physicians
      from the Medical Association office in Pordenone, a modification of the cancer
      questionnaire of Haley and Blanchard (QSPT) was mailed to 916 doctors. Of these,
      605 (60%; 487 male, 118 female; mean age 41 +/- 11 SD) returned the completed
      questionnaire. Within the group of responders, we identified three main
      subgroups, according to their type of activity: general practitioners (175, 29%),
      hospital doctors (235, 39%) and other doctors (195, 32%). In age, sex and
      activity, the only significant difference between responders and non-responders
      was age (mean age 41 and 43 years respectively). Most of the responders (77%)
      stated that they were able to deal with the terminally ill patient and his/her
      needs; 44%, however, admitted that patients' anxiety is sometimes unbearable. For
      the vast majority of the doctors polled (91%), providing a comfortable
      environment for an incurable patient was more important than pursuing aggressive
      treatment, but only 44% were convinced of the uselessness of aggressive care. To
      the question on whether to disclose information about imminent death to allow
      patients to prepare spiritually, 37% answered "No", 38% "Yes", and 25% were
      uncertain. Almost all responders (95%), however, believed in the beneficial
      effect of hope on the terminally ill. Our results suggest that doctors'
      professional and, most of all, socio-demographic and cultural factors determine
      the relationship with the patient on both the emotional and the clinical decision
      making levels.

PMID- 8883227
TI  - Hyponatremia related to medical anticancer treatment.
AB  - Hyponatremia is a common potential complication in cancer patients. It can be
      related to anticancer medical therapy. Vincristine, vinblastine, cisplatin and
      cyclophosphamide are the chemotherapeutic agents most frequently associated with
      hyponatremia. More recently, analogs such as carboplatin and ifosfamide have also
      been incriminated. Hyponatremia is also associated with new immunomodulators
      (interferon, interleukin-2 and levamisole) and monoclonal antibodies. The
      mechanism by which all these drugs act on the sodium steady state is only
      partially known. The syndrome of inappropriate antidiuretic hormone secretion is
      described secondary to vinca alkaloids and cisplatin and possibly with alkylating
      agents. Renal salt wasting is described with platinum compounds.

PMID- 8883228
TI  - A retrospective study of the psychiatric management and outcome of delirium in
      the cancer patient.
AB  - This report describes the evaluation and treatment of delirium in the cancer
      patient in a major comprehensive cancer center. Ninety consecutive cases of
      delirium seen by the inpatient psychiatry consultation/liaison service were
      analyzed in a retrospective fashion to evaluate demographic information, alcohol
      use, central nervous system disease, coexisting medical disease, and past
      psychiatric history. Delirium cases were divided into hyperalert, hypoalert, and
      mixed subtypes. For these three subtypes, medication profiles including dose of
      medication, duration of delirium, outcome, and the venue where the delirium began
      were also evaluated. The hyperalert subtype of delirium was the commonest type
      observed (71%) and had the shortest duration (P < 0.0001) and best outcome (P <
      0.001). The patients with a hyperalert delirium subtype were treated with the
      least amount of haloperidol (P < 0.0001). Patients were delirious for longer when
      the delirium began in the intensive-care units (P < 0.04). In general, patients
      who received no haloperidol experienced delirium of longer duration (P < 0.02)
      than those receiving haloperidol. Since the data represent patients who were
      referred for psychiatric treatment, this may explain the increased number of
      hyperalert deliriums and, therefore, the generalizability of the results is
      limited. Delirium in the cancer patient is particularly problematic given the
      coexisting medical problems these patients experience. Because the outcome of
      delirium is better when the duration is shorter, it is important for clinicians
      to be sensitive to early symptoms so that treatment can be implemented faster,
      leading to less morbidity and mortality.

PMID- 8883229
TI  - Outpatient antibiotic treatment in low-risk febrile neutropenic cancer patients.
AB  - Traditionally febrile neutropenic patients have been treated with parenteral
      antibiotics in an inpatient setting; however, recent work by several
      investigators has demonstrated successful treatment with both parenteral and oral
      antibiotics in an ambulatory environment. This has been accomplished by
      identification of low-risk neutropenic patients, advances in broad-spectrum
      antibiotics with long half-lives and stabilities, the introduction of the oral
      quinolones, home health-care initiatives, improvements in vascular access
      devices, and development of technically enhanced antibiotic delivery systems.
      Outpatient antibiotic therapy for febrile episodes in low-risk neutropenic
      patients should now be considered an acceptable alternative to hospital-based
      treatment. This review focuses on the development and rationale of risk
      stratification and examines the results of various outpatient antibiotic trials
      recently completed.

PMID- 8883231
TI  - Acute and anticipatory emesis in breast cancer patients.
AB  - A group of 90 breast cancer patients undergoing chemotherapy were assessed
      prospectively to estimate the prevalence of acute (post-treatment) and
      anticipatory emesis in the 1990s. For this purpose, two protocols of chemotherapy
      were analysed separately: cyclophosphamide/methotrexate/5-fluorouracil (CMF) and
      5-fluorouracil/doxorubicin/cyclophosphamide (FAC). All patients were treated with
      antiemetic therapy, which included one corticoid plus ondansetron (in the FAC
      regimen), or one corticoid plus thiethylperazine (in the CMF regimen). For at
      least one cycle of chemotherapy 86.1% and 91.7% patients in the FAC protocol
      presented vomiting and nausea respectively: 11.1% had anticipatory vomiting and
      30.6% had anticipatory nausea. In the CMF protocol, 79.6% had post-chemotherapy
      vomiting and 71.7% had post-chemotherapy nausea associated with at least one
      cycle. In this group, 7.4% had anticipatory vomiting and 16.6% had anticipatory
      nausea. A high proportion of patients suffered anticipatory anxiety in both
      groups (75% in FAC, 74.1% in CMF). The stimuli most frequently associated with
      the appearance of anticipatory emesis were olfactory stimuli and cognitive
      stimuli. In summary, as a result of the advances made in antiemetic control
      during the last decade, the severity of chemotherapy-induced emesis seems to have
      significantly decreased, but the prevalence of these symptoms along the course of
      the treatment still remains high.

PMID- 8883230
TI  - Prophylactic antibiotics eliminate bacteremia and allow safe outpatient
      management following high-dose chemotherapy and autologous stem cell rescue.
AB  - This study examines the effectiveness of prophylactic ciprofloxacin and rifampin
      following high-dose chemotherapy and autologous stem cell rescue (HDC/ ASCR).
      Specific endpoints included the incidence of fever, clinically documented
      infection, bacteremia, and readmission rates from an outpatient bone marrow
      transplant setting following infection or fever. A group of 97 patients receiving
      134 cycles of HDC/ASCR were studied. Patients were given ciprofloxacin 750 mg
      p.o. twice daily and rifampin 300 mg p.o. twice daily beginning on the day of
      stem cell reinfusion (24-48 h after completion of high-dose chemotherapy). Most
      patients were either discharged to an outpatient setting following completion of
      their chemotherapy or received all of their chemotherapy in an outpatient
      setting. Febrile neutropenia was treated with empirical antibiotics in an
      outpatient setting unless it was complicated by hypotension, renal failure,
      severe mucositis or other problems. The median duration of neutropenia (absolute
      neutrophil count below 500/mm3) was 7 days. Neutropenic fever occurred in 62% of
      patients but clinically documented bacterial infection occurred in only 2 (1.5%)
      patients during their neutropenic period. No bacteremia was noted. Readmission to
      the hospital following fever or infection occurred in 26% of patients maintained
      in the outpatient setting. There were no deaths from a bacterial infection in
      this study although 1 patient (0.7%) died from aspergillosis. Prophylactic
      ciprofloxacin and rifampin is a well-tolerated and highly effective combination
      that effectively decreases the risk of both gram-positive and gram-negative
      bacterial infection following HDC/ASCR. It facilitates outpatient management of
      myelosuppressed patients receiving autologous stem cell rescue.

PMID- 8883232
TI  - A double-blind, placebo-controlled trial of i.v. dolasetron mesilate in the
      prevention of radiotherapy-induced nausea and vomiting in cancer patients.
AB  - The aim of this work was to measure the safety and efficacy of single i.v. doses
      of dolasetron mesilate for the control of emesis caused by single high-dose (at
      least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo
      controlled, multicenter study stratified patients on the basis of being naive or
      nonnaive to radiotherapy. Patients with or without a history of previous
      chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3,
      0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored
      for 24 h. Antiemetic efficacy was assessed from the time to the first emetic
      episode or rescue, from whether there was a complete response (0 emetic episodes
      /no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no
      rescue medication), from the severity of nausea (rated by patients and the
      investigator), and from the investigator's assessment of efficacy. Fifty patients
      completed the study (owing to changing medical practice, enrollment objectives
      were not met; consequently, no significant linear dose trend was expected).
      Pooled dolasetron was superior to the placebo in its effect on the time to first
      emesis or rescue in radiotherapy-nonnaive patients (P = 0.015). Dolasetron was
      statistically superior to the placebo in the overall population on the basis of a
      complete plus major response: 54%, 100%, 93%, and 83% for the placebo and 0.3-,
      0.6-, and 1.2-mg/kg doses respectively (P = 0.002). The low response in the
      highest dose group may be due to an imbalance in the number of chemotherapy
      nonnaive patients in that group. Dolasetron was superior to the placebo on the
      basis of nausea assessed by the investigator (P = 0.024) and administration of
      rescue medication (P = 0.006). Complete response at the 0.3-mg/ kg dose was
      superior to results with the placebo (P = 0.050). Treatment-related adverse
      events were rare, mild to moderate in intensity, and evenly distributed across
      the four groups. Overall, dolasetron mesilate was effective and well-tolerated in
      the control of single, high-dose radiotherapy-induced emesis.

PMID- 8883233
TI  - 5-Hydroxyindoleacetic acid excretion following combination chemotherapy with
      cyclophosphamide, epirubicin and 5-fluorouracil plus ondansetron compared to
      ondansetron alone.
AB  - The aim of the work was to evaluate the impact of cyclophosphamide and
      ondansetron on serotonin metabolism measured by urinary 5-hydroxyindoleacetic
      acid (5-HIAA) excretion. The pattern of urinary 5-HIAA excretion was analysed
      within 24 h following cyclophosphamide, epirubicin and 5-fluorouracil (FEC)
      chemotherapy (n = 14), ondansetron as single agent (n = 31), and in a control
      group (n = 62). 5-HIAA was measured by a fluorescence/polarisation immunoassay.
      Both FEC and ondansetron alone induced a significantly higher 5-HIAA increase
      following the first 12 h after drug administration when compared to the control
      group. The comparison of quantitative variables of 5-HIAA excretion between FEC
      and ondansetron failed to reveal any statistical differences. Cyclophosphamide
      based chemotherapy is associated with only minor increases of 5-HIAA excretion.
      Analysis of 5-HIAA excretion does not help in the description of the
      pathophysiology of cyclophosphamide-induced emesis. In contrast to experimental
      data, serotonin 3 receptor antagonism with ondansetron induces an increase of 5
      HIAA excretion in humans.

PMID- 8883234
TI  - Usage of haloperidol for delirium in cancer patients.
AB  - Although haloperidol is mainly used for the medical treatment of delirium in
      cancer patients, there are no universally accepted guidelines for its usage. We
      accordingly assessed the usefulness in managing delirium of a haloperidol
      treatment regimen in ten delirious cancer patients. The results of this
      preliminary study suggest that, in the management of delirium, appropriate usage
      of haloperidol on the first day is important as it affects the dosage thereafter.

PMID- 8883235
TI  - Octreotide prevents the pathological alterations of bowel obstruction in cancer
      patients.

PMID- 8883236
TI  - The metabolic distinctiveness of emulsified lipid particles in the bloodstream
      and its clinical implications.
AB  - The advantages of administering intravenous fat emulsions are well known.
      Primarily, they are important sources of essential fatty acids; they allow the
      administration of many calories within a small volume; and they are isotonic
      compared to body fluid. In this review, the metabolic distinctiveness of
      parenterally infused fat particles in the bloodstream is evaluated under four
      main headings: (1) the structure and metabolism of fat emulsion particles; (2)
      the metabolism of phospholipid-rich fat emulsion; (3) the interactions between
      fat emulsion particles and plasma lipoproteins; and (4) the acquisition of
      protein moieties (apolipoproteins) by fat emulsion particles and its clinical
      implications.

PMID- 8883237
TI  - Surgical treatment of infective endocarditis complicated by annular infection and
      cerebral infarction.
AB  - The surgical treatment of nine patients with infective endocarditis (IE)
      complicated by annular infection and five with IE complicated by cerebral
      infarction is described herein. In those with annular infection, after thorough
      debridement of the infected tissues, valve replacement was performed at the
      original position in five, at the supraannular position in three, and one
      underwent a translocation procedure. Aortic valve replacement was able to be
      performed at the original position in two patients by closing the defect at the
      aortic annulus with a patch after through debridement. The five patients who
      underwent original valve position replacement recovered well. Of the three who
      underwent supraannular position replacement, two died of septicemia after a redo
      operation, and one received pacemaker implantation. The patient undergoing the
      translocation procedure died of intestinal infarction. In the five patients who
      suffered cerebral infarction due to embolus of the vegetation, valve replacement
      was performed between 40 h and 5 months after its onset. Although one patient
      died of the rapid progression of brain damage, the other four are alive and well,
      including two who developed mycotic cerebral aneurysm in the infarcted areas. In
      conclusion, early surgery for IE is mandatory irrespective of active infection,
      due to the high mortality and morbidity associated with serious sequelae such as
      annular abscess or cerebral infarction.

PMID- 8883238
TI  - The accuracy of color Doppler flow imaging for the detection of symptomatic deep
      venous thrombosis in Chinese patients.
AB  - To evaluate the ability of color Doppler flow imaging (CDFI) to detect deep
      venous thrombosis (DVT), which is difficult to diagnose clinically, 67 limbs of
      60 patients who presented with clinical signs strongly indicative of DVT during
      the period between June 1988 and June 1992, were examined. The iliac, common
      femoral, and superficial femoral veins were assessed with the patient in the
      supine position, and the popliteal vein was examined with the patient prone.
      Gentle but firm compression with the transducer probe was used to test for the
      presence of DVT. Ascending contrast venograms were also obtained within 24 h
      after the ultrasound procedure, with venography being used as the standard for
      comparison with CDFI. DVT was identified in 63 limbs by contrast venography and
      in 62 limbs by CDFI. The sensitivity and specificity of CDFI were 98.4% and 100%,
      respectively, while the positive and negative predictive values were 100% and
      80%, respectively. The thromboses were classified into three patterns: the
      filling type, the local type, and mural thrombus, detected in 63%, 27%, and 10%,
      of the limbs respectively, with the filling type being the most common in this
      series. The results of our study illustrated that CDFI is highly sensitive and
      specific for detecting symptomatic DVT and that it should be gradually
      substituted for venography in such patients.

PMID- 8883239
TI  - Changes in liver blood flow after hepatectomy in conscious dogs.
AB  - Hepatic circulation after hepatectomy was investigated in conscious dogs under
      fasting and feeding conditions. After a 40% hepatectomy, both the hepatic
      arterial and portal blood flow were measured simultaneously using ultrasonic
      transit time flowmeters. During fasting, the total hepatic blood flow (i.e., the
      sum of arterial and portal blood flow) changed in a biphasic pattern after
      hepatectomy. The first peak (517.9 +/- 42.7 ml/min; 130.1% of preoperative flow)
      was seen on the 1st postoperative day (POD) and the second peak (444.8 +/- 25.6
      ml/min; 112.7% of preoperative flow) occurred on the 7th POD. The portal flow
      demonstrated the same biphasic changes as the total hepatic flow, although the
      hepatic arterial flow showed only the first peak. A heart rate analysis suggested
      that the first peak was probably due to hyperdynamic circulatory conditions, as
      has been previously reported. In addition, the existence of the second peak was
      established by the present study. The postprandial hepatic blood flow decreased
      during the first 2 weeks postoperatively, but exceeded the presurgical levels on
      PODs 21 and 28.

PMID- 8883240
TI  - Activation of neutrophil function by recombinant human granulocyte colony
      stimulating factor improves the survival of rats with peritonitis.
AB  - We examined the effects of recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) and cefmetazole sodium on survival, neutrophil count, and
      neutrophil function in rats with peritonitis produced by cecal ligation and
      puncture. Rats with peritonitis received either rhG-CSF (50 or 100 micrograms/kg)
      with or without cefmetazole (50 mg/kg) for 3 days, cefmetazole alone, or no
      treatment and were evaluated as controls. The mortality rate of all treated rats
      was significantly lower than that of the untreated rats. The survival rate was
      57.1% for the rats given both rhG-CSF and cefmetazole, but there was no
      significant improvement of survival as compared with cefmetazole therapy alone.
      Treatment with rhG-CSF at 100 micrograms/kg caused the circulating neutrophil
      count to increase significantly. The phagocytic activity for latex beads and
      neutrophil H2O2 production showed a greater enhancement by phorbol myristate
      acetate (PMA) in the untreated rats, thus indicating that neutrophils from
      treated rats were more activated. These findings show that rhG-CSF can improve
      survival and neutrophil function in rats with peritonitis, while combined therapy
      with cefmetazole was also found to be beneficial.

PMID- 8883241
TI  - Leiomyomatosis peritonealis disseminata occurring in a postmenopausal woman:
      report of a case.
AB  - Leiomyomatosis peritonealis disseminata (LPD) is a rare condition, reported to
      occur chiefly in premenopausal women. In fact only five cases of LPD in
      postmenopausal women have been documented in the English literature. We report
      herein a case of LPD occurring in a postmenopausal woman who had undergone a
      total hysterectomy 15 years earlier and received no subsequent hormonal therapy.
      At laparotomy, a cystic mass measuring 10.0 x 12.0 cm was found adhering to the
      jejunum. There were also innumerable tumor nodules ranging from 0.5 to 5.0 cm in
      diameter attached to the antimesenteric borders of the intestine and the parietal
      peritoneum. We resected the cystic main tumor together with 20 cm of jejunum to
      release the intestinal obstruction. Several daughter tumors were also resected as
      biopsies for histological examination. Histologically, the lesions were multiple
      and consisted of proliferating smooth muscle cells with rod-like nuclei showing
      extremely rare mitotic figures, confirming a diagnosis of LPD.

PMID- 8883242
TI  - Intestinal obstruction caused by splenic volvulus: report of a case.
AB  - Torsion of a wandering spleen is rare, usually presenting as acute abdomen, and
      is commonly misdiagnosed. In special cases, ultrasonography, arteriography, and
      additional scintigraphy are extremely valuable in the preoperative diagnostic
      management. We herein present an unusual case of torsion of a wandering spleen in
      a 19-year-old female. The presenting symptom was acute gastrointestinal
      obstruction due to pressure of the enlarged and ptotic spleen in the pelvis. The
      intestinal obstruction with signs of peritonitis made a laparatomy with removal
      of the infarcted spleen imperative. After the operation, the patient made a
      complete recovery.

PMID- 8883243
TI  - Adenocarcinoma in the anal canal associated with a fistula: report of a case.
AB  - Adenocarcinoma in the anal canal associated with an anal fistula is extremely
      rare, and in most cases its origin is difficult to ascertain because the primary
      sites have already been destroyed before any diagnosis of malignancy is able to
      be made. We report herein the case of a 62-year-old man found to have papillary
      adenocarcinoma with partial mucinous carcinoma associated with an anal fistula.
      The tumor was not exposed to the mucosal surface of the anal canal or rectum and
      an abdominoperineal resection was carried out. Macroscopic findings suggested
      that the tumor had developed from the anal fistula; however, the tumor showed a
      positive results when tested for O-acetylated sialic acids. This test also proved
      positive in the mucus of normal rectal mucosa, but not in the mucus of the anal
      glands. We speculated that the results of these tests may indicate that this
      tumor could have originated from the rectal mucosa, from where it migrated into
      the anal fistula.

PMID- 8883244
TI  - Perianal extramammary Paget's disease associated with primary linitis plastica of
      the rectum: report of a case.
AB  - We report herein a case of perianal extramammary Paget's disease associated with
      primary linitis plastica of the rectum. An 82-year-old woman was admitted to our
      hospital for investigation and treatment of a perianal eczematous lesion. A skin
      biopsy of the lesion revealed perianal extramammary Paget's disease and a barium
      enema demonstrated diffuse narrowing with an irregular contour at the ampulla
      recti. Under a suspected diagnosis of linitis plastica of the rectum, an
      abdominoperineal resection was performed to resect both the rectal and perianal
      lesions with regional lymphadenectomy. Grossly, marked narrowing and wall
      thickness were observed at the lower rectum, and a histological diagnosis of
      signet ring cell carcinoma was confirmed. The perianal eczematous lesion revealed
      many atypical cells with clear cytoplasm, being Paget cells, throughout the
      entire epidermis. Sparse distributions of signet ring cells were also observed in
      the subcutaneous tissue beneath the perianal eczematous lesion. The pathogenesis
      of perianal extramammary Paget's disease in this patient was therefore considered
      to be an intraepidermal extension of primary linitis plastica of the rectum.

PMID- 8883245
TI  - Lupus peritonitis mimicking acute surgical abdomen in a patient with systemic
      lupus erythematosus: report of a case.
AB  - A 25-year-old Japanese woman who had been suffering from systemic lupus
      erythematosus (SLE) for 12 years was admitted to our hospital with a suspected
      diagnosis of peritonitis after suddenly developing severe abdominal pain and
      distention which could not be relieved by treatment with anodyne. Noninvasive
      examinations did not provide enough evidence to rule out acute appendicitis,
      bowel perforation, or ischemia due to vasculitis. Therefore, in consideration of
      the severity of her uncontrollable abdominal pain, an exploratory laparotomy was
      performed. The operative findings revealed nonbacterial peritonitis with a large
      amount of ascites and an edematous small bowel. No perforation of the intestine
      was found. On post-operative day (POD) 3, the severe abdominal pain redeveloped,
      but responded well to steroid pulse therapy. Based on the operative findings and
      her clinical course, the most likely diagnosis was thought to be acute lupus
      peritonitis. It is often difficult to ascertain whether abdominal pain in an SLE
      patients is due to lupus peritonitis or to an underlying cause requiring surgery.
      Thus, it is essential that continuous and careful assessment of the surgical
      abdomen is performed when a patient with SLE develops acute abdominal pain, and
      if a surgical condition cannot be ruled out, a laparotomy should be performed
      without delay.

PMID- 8883246
TI  - Transient hepatofugal portal blood flow after hepatectomy in a patient with
      cirrhosis: report of a case.
AB  - We report herein the case of a 60-year-old man who developed hepatic failure with
      simultaneous transient hepatofugal portal blood flow after undergoing hepatectomy
      for hepatocellular carcinoma accompanied by cirrhosis with a splenorenal shunt.
      The transient hepatofugal portal blood flow was detected by color Doppler
      ultrasonography. Following this case report, the possibility of a relationship
      between hepatofugal portal blood flow, portal-systemic shunts, and postoperative
      hepatic failure is discussed.

PMID- 8883247
TI  - Hepatocellular carcinoma associated with precirrhotic primary biliary cirrhosis
      successfully treated by a right hepatic lobectomy: report of a case.
AB  - We report herein the case of a 69-year-old woman in whom hepatocellular carcinoma
      (HCC) arising in the precirrhotic phase of primary biliary cirrhosis (PBC) was
      successfully managed by a right hepatic lobectomy. The patient, who had never
      received a blood transfusion, had a 4-year history of asymptomatic PBC of
      Scheuer's histological classification stage II. Abdominal computed tomography
      (CT) revealed a mass measuring 4.0 cm in the right hepatic lobe, and a right
      hepatic lobectomy was performed in consideration of her good liver function and
      the deep location of the tumor in the right lobe. The patient has remained well
      without any evidence of recurrent disease for 4 years since her operation. A
      review of the literature revealed only two cases of successful partial
      hepatectomy, but none of major hepatectomy. Most of the reported cases had been
      treated with transcatheter arterial embolization (TAE) and were associated with
      poor survival. Our experience of this patient indicates the potential value of
      hepatectomy as an alternative to TAE in selected patients with resectable disease
      and good hepatic function.

PMID- 8883248
TI  - Myofibroblastoma of the breast: report of a case.
AB  - We report herein the case of a 36-year-old woman in whom a breast mass was
      diagnosed histologically and immunohistochemically as myofibroblastoma (MFB). The
      patient initially presented with a breast mass measuring 1.0 x 1.5 cm which was
      demonstrated by mammography as a well-circumscribed, round tumor with two coarse
      calcifications. On ultrasonography, the tumor showed slight shadowy internal
      echoes. Histological examination of an excisional biopsy specimen demonstrated a
      tumor consisting of spindle-shaped cells and broad bands of hyalinized collagen
      with cartilaginous and osseous components, but no epithelial components were
      observed. Immunohistochemically, the tumor cells were diffusely positive for
      alpha smooth muscle actin, and a diagnosis of MFB was made. A wide excision of
      the breast was performed as a secondary procedure, and the patient is well and
      free from recurrence 1 year after her operation. We present this case to stress
      the need for breast surgeons to be aware of the existence of MFB when considering
      the differential diagnosis of stromal lesions of the breast to avoid performing
      unnecessarily extensive procedures.

PMID- 8883249
TI  - Granulomatous mastitis diagnosed and followed up by fine-needle aspiration
      cytology, and successfully treated by corticosteroid therapy: report of a case.
AB  - A 36-year-old woman presented to our hospital with a rapidly growing lump in her
      left breast. Fine-needle aspiration (FNA) cytology of the mass revealed many
      epithelioid cells admixed with multinucleated Langhans-type giant cells,
      neutrophils, lymphocytes, and stromal cells, leading to a diagnosis of
      granulomatous mastitis. This report describes the clinical course of this patient
      in whom granulomatous mastitis was successfully treated with corticosteroid
      therapy. Special reference is made to the usefulness of FNA cytology in the
      diagnosis and follow-up of this disease.

PMID- 8883250
TI  - Secundum atrial septal defect associated with mitral valve cleft: report of a
      case with chromosomal syndrome of trisomy 3p.
AB  - A 4-year-old boy was diagnosed as having a chromosomal abnormality with trisomy
      3p associated with a secundum atrial septal defect and a cleft of the anterior
      mitral leaflet. His craniofacial features showed microcephaly, micrognathia,
      ocular hypertelorism associated with epicanthus, and low-set ears. Moderate
      mental retardation and hypoplasia of the penis were also noted. A left
      ventriculogram demonstrated grade 2 mitral regurgitation according to the
      Sellers' classification with a prolapsing of the mitral leaflets. A cleft of the
      anterior mitral leaflet was detected at the time of operation. The secundum
      atrial septal defect was directly closed and the mitral cleft was repaired. This
      is the first report of trisomy 3p associated with an atrial septal defect and a
      mitral valve cleft.

PMID- 8883251
TI  - Aneurysm of a patent ductus arteriosus in an adult.
AB  - An adult patient with a spontaneous aneurysm of a patent ductus arteriosus was
      successfully treated. The lumen of the aneurysm communicated with the distal
      aortic arch and the pulmonary artery. Closure of the pulmonary arterial orifice
      of the ductus arteriosus and replacement of the inferior wall of the distal
      aortic arch and proximal descending aorta with prosthetic graft were performed
      under partial cardiopulmonary bypass using a centrifugal pump. The postoperative
      recovery was uneventful.

PMID- 8883252
TI  - Successful coronary artery bypass grafting for a patient with myelodysplastic
      syndrome: report of a case.
AB  - We report herein the case of a 61-year-old man with myelodysplastic syndrome
      causing pancytopenia who underwent successful coronary artery bypass grafting
      (CABG). Preoperatively, his hemoglobin (Hb) value was 10.4 g/dl while receiving
      transfusions of 1 or 2 units of red blood cells (RBC) every 2 weeks, his white
      blood cell (WBC) count was 8200/microliter with injections of 100 micrograms
      granulocyte colony-stimulating factor (G-SCF) every 5 days, and his platelet
      count was 4.5 x 10(4)/ microliter without platelet transfusion. From the time the
      pancytopenia was diagnosed in his peripheral blood, he had received a total of
      104 units of RBC and 472 units of platelets, following which he developed an
      antiplatelet antibody, not for a platelet-specific antigen, but for an HLA
      antigen. Thus, HLA-matched platelets were prepared to prevent bleeding caused by
      thrombocytopenia, and the WBC count was elevated preoperatively by G-CSF
      injections. Thereafter, CABG was performed on three vessels. The HLA-matched
      platelets were transfused as the patient was weaned from the extracorporeal
      circulation. As a result of these preparations, we were able to protect the
      patient against bleeding and infection.

PMID- 8883253
TI  - Congenital tracheoesophageal fistula with symptoms commencing at the onset of
      trauma: report of a case.
AB  - Congenital tracheoesophageal fistula without atresia can persist and remain
      undetected without symptoms until adulthood. We have recently encountered such a
      rare case and also conducted a review of the literature. Symptoms are commonly
      present during infancy, but occasionally patients do not develop symptoms until
      adulthood. In this case, it is suggested that the symptoms commenced after the
      redundant mucosal flap or membrane was broken due to a trauma to the chest.

PMID- 8883254
TI  - Ectopic primary pleural thymoma: report of a case.
AB  - We herein report an 83-year-old man who presented with a pleural tumor in the
      right thorax. The tumor was surgically resected and histopathologically diagnosed
      as ectopic primary pleural thymoma lacking any evidence of a mediastinal tumor.
      The clinicopathological aspects of this unusual thymoma are also discussed.

PMID- 8883255
TI  - Congenital diaphragmatic hernia with ipsilateral eventration: a report of two
      cases.
AB  - We report herein the cases of two patients in whom the unusual association of a
      diaphragmatic hernia with eventration of the diaphragm on the same side were
      confirmed. Although various recognized patterns of malformations have been
      described in children with diaphragmatic defects or eventration, to the best of
      our knowledge, this association has never been reported before. Following our
      case reports, the literature on this unusual topic is reviewed and a discussion
      on the possible pathogenesis is presented.

PMID- 8883256
TI  - Lipoblastoma in a 14-year-old boy: report of a case.
AB  - Lipoblastoma is a rare benign neoplasm of embryonal fat which occurs primarily in
      infants and young children. Since 1958, lipoblastoma has been recognized as an
      entity distinct from other benign or malignant tumors of the adipose tissue. This
      tumor presents in two forms: as a localized, well-circumscribed lesion known as
      lipoblastoma, or as a multicentric type of lesion known as lipoblastomatosis. The
      oldest patient documented in the English literature was 8 years of age; however,
      we report herein the case of a 14-year-old boy in whom a lesion excised from the
      left thigh was histopathologically confirmed to be a lipoblastoma.

PMID- 8883257
TI  - Successful management of a giant spinal arteriovenous malformation with multiple
      communications between primitive arterial and venous structures by embolization:
      report of a case.
AB  - A 47-year-old woman was admitted to our hospital with a giant spinal
      arteriovenous malformation (AVM) causing heart failure and thoracic myelopathy.
      Angiography revealed that the spinal AVM had multiple feeding vessels branching
      from the 5th through 12th intercostal arteries. The drainage vein flowed to the
      azygos vein and superior vena cava. The AVM destroyed the 7th thoracic vertebra.
      The cardiac output was 16.7l/min and the shunt ratio was 64% before treatment.
      Embolization with cyanoacrylate was performed because the operation was
      considered to be associated with a significant risk of paraplegia and organ
      ischemia. The cardiac output decreased to 11.6l/min and the shunt ratio was
      reduced to 32%. After embolization the patient demonstrated no symptoms of either
      heart failure or sensory deficits. During embolization, provocative tests using
      sodium amytal and lidocaine with magnetic stimulation were also performed. The
      above findings suggest that provocative tests and magnetic stimulation are useful
      to predict paraplegia, which could result from embolization while, in addition,
      embolization is considered to be a useful treatment for multiple shunt and nidus
      in this region.

PMID- 8883258
TI  - The positive relationship between the expression of CD44 variant 6 and prognosis
      in colorectal cancer.
AB  - CD44 variant 6 (CD44 v6) is well known as a useful marker of tumor progression;
      however, its relationship to prognosis has not yet been elucidated. In this
      study, we investigated the expression of CD44 v6 in colorectal cancer to analyze
      its relationship to hepatic metastasis as well as to prognosis. Tumor tissues
      were obtained from 42 patients with colorectal cancer who underwent curative
      resection with follow-up periods ranging from 5.9 to 71.3 months. There were 21
      patients (50%) whose tumors were positive for CD44 v6, with no significant
      difference between colon and rectal cancer. CD44 v6 staining was significantly
      related to Dukes' classification as well as to hepatic metastasis. The 5-year
      survival rate was significantly higher in patients with CD44 v6 negative cancer
      (84%) than in those with CD44 v6 positive cancer (31%). Thus, we concluded that
      CD44 v6 could be a reliable prognostic indicator, as well as a predictor of
      metastatic potential after curative surgery for colorectal cancer.

PMID- 8883259
TI  - Centrifugal pump-assisted venous bypass between the superior mesenteric vein and
      the umbilical vein during portal vein resection.
AB  - We describe herein our method of performing centrifugal pump-assisted venous
      bypass between the superior mesenteric vein and the umbilical vein, developed
      with the aim of preventing congestion of the small intestine and promoting strong
      and constant hepatic blood flow during portal vein resection. By using this
      bypass method, portal vein resection and reconstruction was able to be carried
      out with ease and safety in six patients undergoing surgery for a pancreatic mass
      or cancer. No coagulation abnormalities, thrombocytopenia, leukocytopenia, severe
      liver dysfunction, or portal vein thrombosis developed in any of the patients
      postoperatively. Thus, we highly recommend this simple and reliable method of
      bypass when portal vein resection is being performed.

PMID- 8883260
TI  - Ala244Val is a common, probably ancient mutation causing factor VII deficiency in
      Moroccan and Iranian Jews.
AB  - We investigated the molecular basis for factor VII (FVII) deficiency in Israel
      and found that 13 patients were homozygous and 10 heterozygous for a C to T
      substitution at nucleotide 10648 of the FVII gene. This predicted an Ala244Val
      change and was associated with decreased FVII activity and antigen level. Of the
      36 Ala244Val positive alleles, 20 were observed in patients of Moroccan origin,
      10 in Iranian-Jewish patients and 6 in patients of other origins. A computer
      model of the serine protease domain of FVII suggested that the Ala244Val
      substitution may cause distortion of the entire protein structure. Intragenic
      polymorphic sites analyses disclosed a founder effect for the Moroccan and
      Iranian-Jewish patients. A survey of the Ala244Val mutation revealed an allele
      frequency of 1:42.5 in Moroccan Jews and 1:40 in Iranian Jews. As Moroccan Jews
      have been separated from Iranian Jews for more than two millennia, the data
      suggest that the Ala244Val mutation occurred in ancient times.

PMID- 8883261
TI  - A mutant (Arg327-->His) GPIIb associated to thrombasthenia exerts a dominant
      negative effect in stably transfected CHO cells.
AB  - This work reports the structural and functional characterization of the platelet
      glycoprotein complex GPIIb-IIIa (integrin alpha IIb beta 3) in a patient of type
      II Glanzmann thrombasthenia, bearing a homozygous G-->A base transition at
      position 1074 of GPIIb that results in an Arg327-->His substitution. CHO cells
      stably transfected with cDNA encoding His327GPIIb showed a drastic reduction in
      the surface expression of alpha IIb beta 3 complex relative to control cells
      transfected with wild type GPIIb. Immunoprecipitation analysis demonstrated that
      GPIIb synthesis, heterodimerization, and short term maturation were not impeded,
      suggesting that conformational changes dependent on Arg327 of GPIIb may play an
      essential role in either the rate of maturation and/or transport of heterodimers
      to the cell surface. Cotransfection of CHO cells with equimolar amounts of cDNAs
      encoding wild type and mutant His327-GPIIb led to a marked reduction in the
      surface expression of alpha IIb beta 3. This novel observation of a dominant
      negative effect of the mutant His 327 alpha IIb subunit provides a molecular
      basis for the reduced platelet alpha IIb beta 3 content observed in the
      heterozygous offspring.

PMID- 8883262
TI  - Genetic characterization of protein C deficiency in Japanese subjects using a
      rapid and nonradioactive method for single-stand conformational polymorphism
      analysis and a model building.
AB  - We studied the molecular basis of protein C deficiency in 28 Japanese families
      including 4 asymptomatic families. Two showed a decreased level of function with
      a normal antigen concentration consistent with type II protein C deficiency and
      the remaining 26 showed type I deficiency with decreases in both function and
      antigen level. All the exons and intron/exon junctions of the protein C gene were
      studied using a strategy combining polymerase chain reaction (PCR) amplification
      and rapid nonradioactive single-strand conformational polymorphism (SSCP)
      analysis. The PCR-amplified fragments with aberrant migration on SSCP analysis
      were sequenced. We identified 11 missense mutations, 1 nonsense mutation, 2
      neutral polymorphisms, 1 frameshift deletion, 1 inframe deletion, and 1 splice
      site mutation. We also identified two different rare mutations in the 5'
      untranslated region in the protein C gene that may be responsible for the
      phenotype. Of these molecular defects, ten were novel. From the results of
      genetic analysis of 47 Japanese families with protein C deficiency reported in
      this and previous studies, Phe139Val and Met364Ile substitutions and a G8857
      deletion were only found in Japanese subjects and seem to be a founder effect. In
      contrast, Arg169Trp and Val297Met substitutions, both occurring at CG
      dinucleotides, were commonly observed in not only Japanese but also Western
      populations, indicating that these are hot spots for mutation in the protein C
      gene. These molecular defects were found in 22 families in total, accounting for
      47% of Japanese families with protein C deficiency. The structural models of the
      second EGF and protease domains of activated wild-type and mutant human protein C
      suggest a possible substrate binding exosite on two loops; one from amino acid
      position 349 to 357 and the other from position 385 to 388, both of which are
      close to each other in the three-dimensional model.

PMID- 8883263
TI  - Hemostatic disorder of uremia: the platelet defect, main determinant of the
      prolonged bleeding time, is correlated with indices of activation of coagulation
      and fibrinolysis.
AB  - Several parameters of primary hemostasis and markers of activation of coagulation
      and fibrinolysis were measured in 48 patients with severe (creatinine clearance <
      20 ml/min) chronic renal failure (CRF) without dialysis and disease or drugs
      affecting hemostasis. Bleeding time (BT) was prolonged in 25/48 patients, and was
      correlated with age of patients, severity of renal failure, hematocrit,
      impairment in platelet aggregation-secretion and decrease in platelet ATP
      content. Defects in von Willebrand factor played no role in the prolongation of
      the BT. Multivariate analysis showed that only platelet dysfunction and severity
      of renal disease were independent predictors of the BT in uremia. The platelet
      functional disorder was significantly correlated with a reduction in platelet ATP
      and ADP. High levels of plasma thrombin-antithrombin complexes (TAT), prothrombin
      fragment F1 + 2, fibrinogen and factor VIIc were observed in patients with CRF,
      as described in prethrombotic states. Plasmin-antiplasmin complexes (PAP),
      fibrinogen and fibrin degradation products (FgDP, FnDP) were significantly
      increased, and the activity of plasminogen activator inhibitor (PAI-1) was
      slightly reduced, denoting an activation of fibrinolysis. A negative correlation
      was found between platelet levels of ATP and ADP with plasma TAT, F1 + 2 and PAP.
      Furthermore, plasma PAI-1 activity was negatively correlated with the BT and was
      lower in patients with prolonged BT as compared with controls and patients with
      normal BT. These links between primary hemostasis and activation of coagulation
      and fibrinolysis suggest that increased intravascular generation of thrombin
      and/or plasmin is an important mediator of the defects in primary hemostasis,
      prolongation of the BT and, probably, bleeding in CRF.

PMID- 8883264
TI  - Increased procoagulant activity of red blood cells from patients with homozygous
      sickle cell disease and beta-thalassemia.
AB  - It has recently been proved that, in vitro, red blood cells (RBCs) from patients
      with homozygous beta-thalassemia behave as procoagulant cells. The procoagulant
      activity of beta-thalassemia RBCs might be the result of an increased exposure of
      procoagulant phospholipids (i.e. phosphatidylserine) in the outer leaflet of the
      membrane. In order to test this hypothesis, we compared the catalytic properties
      of RBCs of patients with beta-thalassemia and homozygous sickle cell disease (SS
      RBCs) with that of controls. The catalytic parameters (Km, kcat) of prothrombin
      activation by factor Xa were determined both in the absence and in the presence
      of RBCs. The turn-over number (kcat) of the reaction was not modified by normal,
      SS- or beta-thalassemia RBCs. The Km was lower in the presence of normal RBCs
      (mean value: 9.1 microM) than in the absence of cells (26 microM). The Km
      measured in the presence of either SS-RBCs (mean value: 1.6 microM) or beta
      thalassemia RBCs (mean value: 1.5 microM) was significantly lower compared to
      normal RBCs (p < 0.001). No significant difference was observed between SS-RBCs
      and beta-thalassemia RBCs. Annexin V, a protein with high affinity and
      specificity for anionic phospholipids, inhibited the procoagulant activity of
      both SS-RBCs and beta-thalassemia RBCs, in a dose-dependent manner. More than 95%
      inhibition was achieved at nanomolar concentrations of annexin V. These results
      indicate that the procoagulant activity of both beta-thalassemia RBCs and SS-RBCs
      may be fully ascribed to an abnormal exposure of phosphatidylserine at the outer
      surface of the red cells.

PMID- 8883265
TI  - Elevated circulating P-selectin in insulin dependent diabetes mellitus.
AB  - Based on findings that showed increased P-selectin expression on platelets and on
      choroidal microvessels of patients with insulin dependent diabetes mellitus
      (IDDM), we hypothesized that also plasma concentrations of circulating (c)P
      selectin would be increased in these patients. The aim of this study was to
      compare the plasma levels of cP-selectin between non-smoking patients with IDDM,
      treated with an intensified insulin therapy, and healthy controls. The study
      design was prospective, cross-sectional and analyst-blinded. Subjects were
      matched individually for sex, age and body mass index. Plasma levels of cP
      selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked
      immunoassays. Forty-two pairs were available for intergroup comparison. Median
      plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml;
      interquartile range: 233-372) were on average 21% higher than those of controls
      (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels
      of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than
      controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no
      correlation between plasma concentrations of cP-selectin and vWF-Ag levels in
      either group (p > 0.05). In conclusion, our results of increased cP-selectin
      levels are in line with increased P-selectin expression on platelets and on
      choroidal microvessels found in patients with IDDM. In view of the currently
      developed small molecule inhibitors of cell adhesion molecules, these independent
      observations together may provide a sound rationale to select P-selectin as a
      target for treating or preventing IDDM-associated micro- or macrovascular
      complications.

PMID- 8883266
TI  - Erythromelalgia in essential thrombocythemia is characterized by platelet
      activation and endothelial cell damage but not by thrombin generation.
AB  - Erythromelalgia, a characteristic aspirin-responsive microvascular thrombotic
      complication in essential thrombocythemia (ET), may develop despite oral
      anticoagulant treatment or treatment with heparin, suggesting that the generation
      of thrombin is not a prerequisite for its development. To study this, a cross
      sectional comparison of the plasma levels of thrombomodulin (TM), platelet factor
      4 (PF4), beta-thromboglobulin (beta-TG), prothrombin fragment 1 + 2 (F1 + 2) and
      total degradation products of fibrin(ogen) (TDP) was made between 5 ET patients
      suffering from erythromelalgia, 16 asymptomatic ET patients and 20 control
      subjects, and after treatment with aspirin, respectively. Furthermore, 2 ET
      patients with a history of erythromelalgia were studied at regular time intervals
      after discontinuation of aspirin until erythromelalgia recurred. As compared with
      asymptomatic ET patients and control subjects erythromelalgia was characterized
      by significantly higher beta-TG and TM levels but no significant differences were
      detected in either F1 + 2 or TDP levels. Treatment of erythromelalgia with
      aspirin resulted in disappearance of erythromelalgic signs and symptoms, which
      was paralleled by a significant decrease of beta-TG and TM levels.
      Histopathologic and immunohistochemical analysis of biopsies derived from
      erythromelalgic skin areas of 2 ET patients showed that erythromelalgic thrombi
      stained positively for von Willebrand factor opposed to only a weak fibrin
      staining. Our data suggest that erythromelalgia is caused by the intravascular
      activation and aggregation of platelets with subsequent sludging or occlusion of
      the acral arterial microvasculature. The generation of thrombin appears not to be
      essential for the formation of these platelet thrombi, thereby giving a plausible
      explanation for the inefficacy of coumadin derivatives and heparin in the
      prevention and treatment of erythromelalgia in essential thrombocythemia.

PMID- 8883267
TI  - Conjunctive administration of intravenous heparin attenuates cross-linked fibrin
      degradation in patients treated with streptokinase.
AB  - Increases in thrombin activity occur in patients treated with streptokinase, but
      conjunctive therapy with intravenous heparin does not appear to improve either
      the rate of early infarct artery patency or survival in patients with acute
      myocardial infarction. In a recent study we found that concentrations of
      fibrinopeptide A, a marker of thrombin-mediated fibrin formation, were lower in
      the first 3 h in patients treated with intravenous heparin (5000 U bolus followed
      by a fixed-dose 1000 U/h infusion, n = 14) compared with subcutaneous (12,500 U
      every 12 h, started 4 h after streptokinse, n = 14) administration, but were
      increased in both groups of patients, consistent with persistent thrombin
      activity. To determine whether the differential effects of the intensity of
      heparinization on thrombin formation were reflected in differences in fibrin
      degradation, we measured cross-linked fibrin degradation products (XL-FDP) before
      and 1, 2, 3, 8, 12, and 24 h after streptokinase in the same cohort of patients,
      with a new ELISA with a D-dimer-specific capture antibody (MAb 3B6) and a fibrin
      specific tag antibody (MAb 1D2, Agen, Brisbane, Australia). The incidence of
      early coronary recanalization assessed by creatine-kinase MM isoforms (increase
      in activity > or = 0.18%/min), was similar in both groups (79 vs 86%).
      Concentrations of XL-FDP were similar in patients with and without
      recanalization, but were lower in patients treated with intravenous compared with
      subcutaneous heparin at 8 h, but the results did not reach statistical
      significance (627 +/- 151 ng/ml versus 1007 +/- 157 ng/ ml, p = 0.06), and were
      significantly lower at 12 h (327 +/- 72 versus 781 +/- 162 ng/ml, p = 0.03 at 12
      h) (mean +/- SEM). Concentrations of cross-linked fibrin degradation products
      were also lower in patients in whom the activated partial thromboplastin time was
      greater than two times the control, compared with those with inadequate
      anticoagulation (498 +/- 105 versus 1084 +/- 179 ng/ml; p = 0.02) (mean +/- SEM).
      Thus, more effective inhibition of thrombin with conjunctive intravenous heparin
      therapy results in less cross-linked fibrin turnover in the first 12 h after
      thrombolysis with streptokinase. This probably reflects decreased fibrin
      formation with therapeutic anticoagulation.

PMID- 8883268
TI  - Cyclosporine therapy for acquired factor VIII inhibitor in a patient with
      systemic lupus erythematosus.
AB  - The case of a 27-year-old woman with systemic lupus erythematosus and development
      of an autoantibody against factor VIII during an exacerbation of her underlying
      disorder is described. Attempts to eliminate the antibody with high dose
      gammaglobulin and repeated courses of cyclophosphamide failed, whereafter she
      received cyclosporine in increasing doses. When therapeutic serum levels of
      cyclosporine were achieved (150-350 ng/ml) the inhibitor rapidly decreased and
      disappeared with a concomitant normalization of the factor VIII levels. Treatment
      with cyclosporine was subsequently reduced and discontinued after one year, and
      at present no inhibitor is detectable. In view of the successful results with
      cyclosporine treatment in 4 of 6 previous cases and in all 3 previous cases with
      autoimmune disorders, this regimen should be evaluated in a systematic manner as
      a potential first line drug in patients with acquired hemophilia and an
      underlying autoimmune disorder.

PMID- 8883269
TI  - Effect of heparin on the activation of factor XI by fibrin-bound thrombin.
AB  - Fibrin-bound thrombin is protected from inactivation by antithrombin III, while
      its coagulant potential is retained. In the presence of heparin, ternary
      complexes between thrombin, fibrin and heparin are formed. In these complexes the
      coagulant activity of thrombin is retained, whereas the anticoagulant activity of
      fibrin-bound heparin is neutralized. The limited effectiveness of heparin in the
      prevention of both venous thrombosis and coronary reocclusion is probably related
      to the protective effect of fibrin on the inactivation of thrombin by anti
      thrombin III. Recently, it has been shown that factor XI can be activated by
      thrombin, resulting in the generation of additional thrombin via the intrinsic
      pathway. This additional thrombin is capable of stabilizing the clot by
      protecting it from fibrinolysis. We studied the effect of heparin on the
      activation of factor XI by fibrin-bound thrombin. First, we used fibrin monomers
      coupled to Sepharose to which thrombin and unfractionated heparin (UFH) were
      bound. Factor XI activation by thrombin was the same in the presence of fibrin
      Sepharose or control-Sepharose. The addition of heparin (0.1 U/ml) resulted in a
      91 and 15-fold enhancement in the presence of control-Sepharose and fibrin
      Sepharose, respectively. Next, we added complexes of heparin, thrombin and fibrin
      monomer to factor XII and XI double-deficient plasma in the presence or absence
      of a reconstituting amount of factor XI. In the presence of factor XI, additional
      fibrin formation was observed indicating that factor XI activation by thrombin in
      complex with fibrin and heparin can take place in plasma. We then studied the
      effect of other heparin-like anticoagulants on the thrombin-mediated factor XI
      activation. UFH enhanced thrombin-mediated factor XI activation 68-fold, LMWH
      (low molecular weight heparin, Fragmin) 12-fold, danaparoid (Orgaran) 3-fold,
      while the pentasaccharide ORG 31540 did not result in an enhancement. Binding
      studies of these anticoagulants to fibrin-Sepharose showed that LMWH bound with
      approximately the same affinity as UFH, while danaparoid and the pentasaccharide
      did not bind to fibrin. We conclude that fibrin-bound thrombin is capable of
      factor XI activation. Furthermore, heparin bound in a complex with fibrin can act
      as a cofactor for this activation. This factor XI activation capacity may play a
      role in the limited effectiveness of heparin. Provided that thrombin-mediated
      factor XI activation plays an important role in vivo, danaparoid and especially
      the pentasaccharide may be better anticoagulants than UFH and LMWH.

PMID- 8883270
TI  - Phosphatidylethanolamine induces specific conformational changes in the
      kininogens recognizable by antiphosphatidylethanolamine antibodies.
AB  - Autoantibodies to the zwitterionic phospholipid (PL), phosphatidylethanolamine
      (PE) have been described in patients with thrombotic diseases. Recently, we
      reported that many antiphosphatidylethanolamine antibodies (aPE) are not specific
      for PE per se, but are directed to plasma proteins which can bind PE, for
      example, high molecular weight kininogen (HK), low molecular weight kininogen
      (LK) and/or proteins in complex with HK, factor XI or prekallikrein. In the
      ELISA, we now show that intact HK binds to all PL tested. By using a monoclonal
      antibody (mAb) to the HK light chain, binding to cardiolipin (CL) was highest
      followed by phosphatidylserine (PS), PE and phosphatidylcholine (PC). By
      contrast, LK bound best to PE, with lesser amounts binding to PC and CL. Many aPE
      recognize only a kininogen-PE complex and neither PE nor kininogen when they are
      tested independently. We now report that these aPE are specific for the kininogen
      PE complex as they do not recognize the kininogens when the latter are presented
      on other PL substrates. This indicates that PE induces unique antigenic
      conformational changes in the kininogens which are not induced when the
      kininogens bind to other PL. The kininogens bind to platelets and endothelial
      cells through an as yet undefined receptor. Since PE is a normal constituent of
      the outer layer of cell and platelet plasma membranes, it is available for the
      kininogens to bind. In vitro studies showed that purified IgG which bound
      kininogen-PE complexes in ELISA also caused platelets to undergo irreversible
      aggregation when stimulated by subthreshold concentrations of bovine thrombin.

PMID- 8883271
TI  - Activation of factor X by factor VIIa complexed with human-mouse tissue factor
      chimeras requires human exon 3.
AB  - In an attempt to define sequence elements in human and mouse tissue factor (TF)
      that are responsible for the species specificity observed in their interaction
      with human factor VIIa (HVIIa), we constructed human-mouse chimeric TF cDNAs,
      inserted them into plasmid vectors, and induced their expression in E. coli.
      Assays for procoagulant activity were carried out with the resulting E. coli
      lysates using (HVIIa) human and mouse (MVIIa). The ratio of the procoagulant
      activities, HVIIa/MVIIa, revealed that human TF exon 3 was essential for activity
      when the TF:VIIa complex was formed with HVIIa. By ligating the maltose binding
      protein (MBP) gene to TF cDNAs it was possible to construct, express and purify
      MBP-TF chimeras as well as to estimate their specific activities. With selected
      MBP-TF chimeras and HVIIa we determined kinetic parameters for the activation of
      human factor X. Replacement of exon 3 in human TF cDNA with the corresponding
      exon from mouse TF cDNA resulted in both lower affinity for HVIIa and failure to
      convert bound HVIIa into a potent protease.

PMID- 8883272
TI  - Postprandial activation of coagulant factor VII by long-chain dietary fatty
      acids.
AB  - Factor VII coagulant activity (FVIIc) is associated with an increased risk of
      fatal ischaemic heart disease (IHD). Several reports have suggested that dietary
      fat intake or hypertriglyceridaemia are associated with elevated levels of FVII.
      This study demonstrates that an intake of long-chain fatty acids sufficient to
      induce postprandial lipaemia in healthy subjects leads to a substantial elevation
      in both FVIIc and the concentration of FVII circulating in the activated form.
      Such an increase in FVIIc could not be induced by medium-chain triglycerides.
      These results suggest that the consumption of a sufficient amount of long-chain
      triglycerides to induce postprandial lipaemia induces the activation of FVII.

PMID- 8883273
TI  - Two recombinant tissue factor reagents compared to conventional thromboplastins
      for determination of international normalised ratio: a thirty-three-laboratory
      collaborative study. The Steering Committee of the UK National External Quality
      Assessment Scheme for Blood Coagulation.
AB  - Recent advances in recombinant technology have led to the development of
      prothrombin time (PT) reagents containing recombinant tissue factor which has
      been lipidated to allow expression of procoagulant activity. In this study we
      have compared International Normalised Ratios (INRs) determined using two such
      reagents and conventional thromboplastins in widespread use in the UK.
      Lyophilised plasma samples from eight different warfarinised patients were
      distributed to 33 laboratories in the UK. Each participant determined prothrombin
      times on 20 local fresh normal plasmas (used to derive mean normal PT and
      calculate INR) and the eight lyophilised samples, using manual technique and the
      following thromboplastins; Recombiplastin (Ortho Diagnostics Ltd); Innovin
      (Baxter Diagnostics Ltd); the conventional thromboplastin in local use. For eight
      plasmas the mean INRs determined with different reagents were as follows: Innovin
      (33 laboratories) - 3.4; Manchester Reagent (MR = 8 laboratories) - 3.4;
      Recombiplastin (33 laboratories) - 3.7; Instrumentation Laboratory (IL = 13
      laboratories) - 4.4. Mean INR results with Recombiplastin were on average 7%
      greater than those obtained with Innovin, 8% greater than results with MR and 18%
      less than INRs with IL thromboplastin. There was no significant difference
      between results obtained with Innovin and MR. In contrast INRs obtained with IL
      were markedly (mean 28%) greater than results obtained with Innovin. This study
      employed lyophilised plasma and it is possible that some of the relationships
      described are influenced by this. However, the lyophilisation process employed
      did not influence the relationship between INRs of warfarinised plasmas obtained
      by the four main reagents described, indicating that the results are relevant to
      routine clinical practice. In conclusion, our data show some important
      differences are present between INRs determined using Recombiplastin, Innovin and
      two conventional thromboplastins.

PMID- 8883274
TI  - Normal binding of calcium to five fibrinogen variants with mutations in the
      carboxy terminal part of the gamma-chain.
AB  - Calcium ions are known to accelerate polymerization of fibrin monomers. Each of
      the two carboxy terminal domains of normal fibrinogen contains one high-affinity
      calcium binding site that seems to be situated close to the polymerization site
      in the gamma-chain. Most hitherto described functionally defective fibrinogen
      variants showed impaired clot formation. Since the tightly bound calcium ions may
      influence the conformation of the polymerization site, the question arises
      whether the abnormal clotting of a dysfibrinogen might be due to defective
      calcium binding. We investigated binding of calcium to fibrinogen and the effect
      of calcium on the clotting properties of five heterozygous fibrinogen variants
      showing normal thrombin-induced fibrinopeptide release but abnormal
      polymerization of fibrin monomers. Each of these dysfibrinogens has one single
      amino acid substitution in the carboxy-terminal part of the gamma-chain:
      fibrinogen Claro (gamma 275 Arg-->His), Milano V (gamma 275 Arg-->Cys), Milano I
      (gamma 330 Asp-->Val), Bern I (gamma 337 Asn-->Lys), and Milano VII (gamma 358
      Ser-->Cys). The shortest thrombin clotting time and the earliest onset of
      turbidity increase were observed in fibrinogen gamma 358 Ser-->Cys; both
      parameters were little affected by calcium concentration. In the variant gamma
      337 Asn-->Lys, the thrombin time was abnormally prolonged at 0.01 mM Ca2+, but it
      was normalized at 1 mM calcium. In contrast, the abnormal fibrin polymerization
      of fibrinogen gamma 330 Asp-->Val was barely improved at increasing calcium
      concentrations. Both variants with the substitution of gamma 275 Arg, the residue
      indispensable for normal D:D interactions, showed the slowest rate of fibrin
      polymerization and the lowest turbidity of fibrin clots at any Ca2+ concentration
      used. High affinity calcium binding was found to be normal in all five fibrinogen
      variants studied, suggesting that their abnormal clotting was not due to
      defective binding of calcium. The gamma-chain in the fragment D1 derived from the
      variant gamma 337 Asn-->Lys was further degraded by plasmin in the presence and
      in the absence of calcium, whereas fragments D1 from the other four gamma-chain
      variants as well as from normal fibrinogen were protected against plasmic
      degradation in the presence of 1 mM Ca2+.

PMID- 8883275
TI  - Experimental pharmacology of hirunorm: a novel synthetic peptide thrombin
      inhibitor.
AB  - Enhanced thrombin activity has been associated with coronary thrombosis and with
      acute and long-term complications following coronary balloon angioplasty.
      Blocking thrombin activity with specific inhibitors is proposed as a promising
      antithrombotic therapy. We describe the anticoagulant and antithrombotic
      properties of hirunorm, a novel synthetic 26-aminoacid peptide thrombin
      inhibitor, in comparison with r-hirudin and hirulog-1. Hirunorm was equipotent to
      hirulog-1 and 1/30 as potent as r-hirudin in blocking alpha-thrombin amidolytic
      activity (IC50 = 10 +/- 2, 15 +/- 1 and 0.3 +/- 0.1 nM, respectively), but it did
      not affect trypsin, plasmin and t-PA activities at 10 microM. All the compounds
      inhibited clot-bound thrombin to clots prepared by thrombin hydrolysis of
      purified fibrinogen in buffer. Hirunorm and hirulog-1 showed similar species
      dependent potency in doubling basal in vitro clotting times of human, rat and
      rabbit plasma (EC200 varied 70 to 200 nM for TT, 0.7 to 16 microM for aPTT and
      0.8 to 17 microM for PT), while r-hirudin was always at least three times more
      active. When assayed by HPLC or by bioassay of the intact peptide, hirunorm was
      stable against alpha-thrombin and plasma hydrolases, but it was catabolized by
      rat liver and kidney enzymes. Venous thrombosis was produced in anaesthetized
      rats by vena cava ligation following a procoagulant serum injection. Intravenous
      and subcutaneous hirunorm inhibited venous thrombosis at doses (< or = 0.3 mg/kg)
      two-three times higher than those of r-hirudin. Hirulog-1 was as active as
      hirunorm only after i.v. infusion. Arterial thrombosis was obtained in the
      anaesthetized rat by chemical (FeCl2) stimulation of a common carotid and i.v.
      infused hirunorm (1-3 mg/kg/30 min) inhibited it dose-dependently; r-hirudin was
      partly active only at 3 mg/kg, but hirulog-1 was inactive at either dose. Full
      antithrombotic doses of hirunorm did not affect the bleeding time as measured
      from punctured mesenteric vessels, in anaesthetized rats. In conclusion, hirunorm
      is a potent peptide thrombin inhibitor endowed with antithrombotic activity in
      models of venous and arterial thrombosis.

PMID- 8883276
TI  - Two new frequent dimorphisms in the protein S (PROS1) gene.
AB  - Two new polymorphisms were identified in the protein S gene (PROS1): an intronic
      T/A-dimorphism (PIPS1) in intron K, and an exonic C/A-dimorphism (PEPS2), located
      in the 3'untranslated trailer of exon 15. Allelic frequencies of 24% (PIPS1-A)
      and 17% (PEPS2-A) respectively, were determined in the normal population. The
      identification of an intronic and an exonic PROS1 dimorphism, in addition to the
      known BstXI dimorphism, enlarges the molecular tool box for gene analysis and
      transcript quantification in hereditary protein S deficiency. Haplotype analysis
      showed that variability of both new polymorphisms occurred almost exclusively in
      the A-allele of the known intragenic BstXI dimorphism. Therefore, PEPS2 and PIPS1
      are especially valuable in individuals homozygous for the BstXI A-variant.

PMID- 8883277
TI  - The interaction of protein S with the phospholipid surface is essential for the
      activated protein C-independent activity of protein S.
AB  - Protein S is a vitamin-K dependent glycoprotein involved in the regulation of the
      anticoagulant activity of activated protein C (APC). Recent data showed a direct
      anticoagulant role of protein S independent of APC, as demonstrated by the
      inhibition of prothrombinase and tenase activity both in plasma and in purified
      systems. This anticoagulant effect of protein S can be explained either by a
      direct interaction of protein S with one of the components of the complexes
      and/or by the interference with the binding of these components to phospholipid
      surfaces. During our investigation we noted that protein S preparations purified
      in different ways and derived from different sources, expressed discrepant APC
      cofactor and direct anticoagulant activity. In order to elucidate these
      differences and to study the mechanism of the APC-independent activity of protein
      S, we compared the protein S preparations in phospholipid-binding properties and
      anticoagulant activity. The dissociation constant for the binding of protein S to
      immobilized phospholipids ranged from 7 to 74 nM for the different protein S
      preparations. APC-independent inhibition of both prothrombinase and tenase
      activity performed on phospholipid vesicles and in plasma showed a strong
      correlation with the affinity for phospholipids. The APC-independent activity
      could be abolished by monoclonal antibodies that were either calcium-dependent
      and/or directed against epitopes in the Gla-region of protein S, suggesting that
      the protein S-phospholipid interaction is crucial for the APC-independent
      anticoagulant function of protein S. Protein S preparations with a low APC
      independent activity expressed a high APC-cofactor activity suggesting that the
      affinity of protein S for phospholipids is of less importance in the expression
      of APC-cofactor activity of protein S. We conclude that high affinity
      interactions of protein S with the membrane surface are essential for the direct
      anticoagulant activity of protein S and we suggest that inhibition of the
      prothrombinase and the tenase complex by protein S is a consequence of the
      occupation of the phospholipid surface by protein S molecules.

PMID- 8883278
TI  - A prothrombinase-based assay for detection of resistance to activated protein C.
AB  - In this paper we present a new method for the detection of resistance to
      activated protein C (APC) that is based on direct measurement of the effect of
      APC on the cofactor activity of plasma factor Va. The factor V present in a
      diluted plasma sample was activated with thrombin and its sensitivity towards APC
      was subsequently determined by incubation with phospholipids and APC. The loss of
      factor Va cofactor activity was quantified in a prothrombinase system containing
      purified prothrombin, factor Xa and phospholipid vesicles and using a chromogenic
      assay for quantitation of thrombin formation. The reaction conditions were
      optimized in order to distinguish normal, heterozygous and homozygous APC
      resistant plasmas. Maximal differences in the response of these plasmas towards
      APC were observed when factor Va was inactivated by APC in the absence of protein
      S and when the cofactor activity of factor Va was determined at a low factor Xa
      concentration (0.3 nM). Addition of 0.2 nM APC and 20 microM phospholipid
      vesicles to a 1000-fold diluted sample of thrombin-activated normal plasma
      resulted in loss of more than 85% of the cofactor activity factor Va within 6
      min. Under the same conditions, APC inactivated approximately 60% and
      approximately 20% of the factor Va present in plasma samples from APC-resistant
      individuals that were heterozygous or homozygous for the mutation Arg506-->Gln in
      factor V, respectively. Discrimination between the plasma samples from normal and
      heterozygous and homozygous APC-resistant individuals was facilitated by
      introduction of the so-called APC-sensitivity ratio (APC-sr). The APC-sr was
      defined as the ratio of the factor Va cofactor activities determined in thrombin
      activated plasma samples after 6 min incubation with or without 0.2 nM APC and
      was multiplied by 100 to obtain integers (APC-sr = ?factor Va+APC square root of
      factor Va-APC? x 100). Clear differences were observed between the APC-sr of
      plasmas from normal healthy volunteers (APC-sr: 8-20, n = 33) and from
      individuals that were heterozygous (APC-sr: 35-50, n = 17) or homozygous APC
      resistant (APC-sr: 82-88, n = 7). There was no mutual overlap between the APC-sr
      of normal plasmas and plasmas from heterozygous or homozygous APC resistant
      individuals (p < 0.0001). In all cases our test gave the same result at the DNA
      based assay. Since the test is performed on a highly diluted plasma sample there
      is no interference by conditions that affect APC resistance tests that are based
      on clotting time determinations (e.g. coagulation factor deficiencies, oral
      anticoagulation, heparin treatment, the presence of lupus anticoagulants,
      pregnancy or the use of oral contraceptives). Furthermore, we show that part of
      the factor Va assay can be performed on an autoanalyzer which increases the
      number of plasma samples that can be handled simultaneously.

PMID- 8883279
TI  - Haemostatic parameters and lifestyle factors in elderly men in Italy and The
      Netherlands.
AB  - The association between plasma fibrinogen, factor VII, factor X, activated
      partial thromboplastin time, antithrombin III and the lifestyle factors cigarette
      smoking, alcohol use, fat intake and physical activity was assessed in 802 men
      aged 70-90 years in Zutphen (The Netherlands), Montegiorgio and Crevalcore
      (Italy). Smoking was positively associated with fibrinogen, also after adjustment
      for other lifestyle factors, age, use of anticoagulants and aspirin like drugs,
      body mass index, and history of myocardial infarction. Alcohol use was associated
      with increased levels of factor X and decreased levels of antithrombin III. Fat
      intake was positively associated with antithrombin III. Between cohorts,
      considerable differences were observed in levels of haemostatic parameters and
      the lifestyle factors. Compared to the mediterranean cohorts the Zutphen cohort
      showed the highest levels of fibrinogen and factor VII. Differences in lifestyle
      factors could, however, not explain differences between cohorts in levels of any
      of the haemostatic parameters, despite the observed associations between
      lifestyle factors and haemostatic parameters.

PMID- 8883280
TI  - Plasminogen activator inhibitor 1 is elevated in the children of men with
      premature myocardial infarction.
AB  - To assess whether plasminogen activator inhibitor 1 (PAI-1) activity is elevated
      in the progeny of young coronary men, 193 young subjects were recruited and
      divided into two groups. Group A consisted of 104 children whose fathers had
      suffered a myocardial infarction before the age of 55 ("cases"). Eighty-nine
      young subjects matched for age, sex, body mass index (BMI) and smoking habits
      without familial history of coronary artery disease (CAD) served as controls
      (group B). Children with a family history of diabetes mellitus or hypertension
      were excluded from both groups. We measured PAI-1 activity, tissue-type
      plasminogen activator (t-PA) antigen, a2-antiplasmin, fibrinogen, lipids and
      apolipoproteins in both groups. PAI-1 activity levels were also determined in the
      men who suffered a premature myocardial infarction 4 months after their
      discharge. PAI-1 activity levels were higher in cases compared to controls (3.13
      +/- 1.9 vs 2.17 +/- 1.9 U/ml, p = 0.0014). t-PA antigen and a2-antiplasmin did
      not differ significantly between the two groups, while fibrinogen, total
      cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and
      lipoprotein(a) were significantly higher in group A. PAI-1 was positively
      correlated with triglycerides (r = 0.22, p = 0.024), apolipoprotein B (r = 0.21,
      p = 0.039) and fibrinogen (r = 0.22, p = 0.029) in cases and with BMI in both
      cases (r = 0.37, p = 0.0003) and controls (r = 0.23, p = 0.044). In stepwise
      multiple regression analysis, only apolipoprotein B (p = 0.008) and BMI (p =
      0.0014) were significant determinants of PAI-1 activity in cases. There was also
      a positive correlation between PAI-1 activity levels of the affected fathers and
      their children (r = 0.30, p = 0.01). The present data support the hypothesis that
      elevated PAI-1 levels in the offspring of men with premature myocardial
      infarction impair their fibrinolytic capacity contributing to their familial
      predisposition to CAD.

PMID- 8883281
TI  - Long-term treatment with growth hormone decreases plasminogen activator inhibitor
      1 and tissue plasminogen activator in growth hormone-deficient adults.
AB  - The syndrome of growth hormone deficiency (GHD) in adults is associated with
      premature atherosclerosis, increased cardiovascular mortality, abnormal
      lipoprotein patterns and abnormal body composition. We have previously shown that
      GH-deficient adults have increased concentrations of fibrinogen and plasminogen
      activator inhibitor (PAI-1) activity. The aim of the present investigation was to
      study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two
      years of treatment with recombinant human GH (12 micrograms/kg body weight/day).
      The impact of the contemporary changes in metabolic variables and body
      composition on coagulation and fibrinolysis was studied. The patients received
      conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1
      activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels
      decreased during the GH treatment period (p < 0.05). The decrease was more
      pronounced in patients with high pre-treatment levels of the different variables.
      alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during
      two years of GH treatment. Fibrinogen concentrations tended to decrease after two
      years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were
      unchanged. von Willebrand factor demonstrated a transient decrease after 18
      months of GH treatment. The coagulation inhibitor, protein C, decreased (p <
      0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p <
      0.01), but blood glucose did not differ after two years of GH treatment. Serum
      high-density lipoprotein cholesterol, total cholesterol and triglycerides were
      unaltered. Body fat decreased during the initial GH treatment but was unaltered
      after two years, while lean body mass increased (p < 0.001) and the waist over
      hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1
      activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment.
      These changes may be a direct effect of GH itself or may be secondary to the
      favourable changes in body composition. It remains to be seen whether changes in
      these fibrinolytic variables during rhGH treatment reduces the cardiovascular
      risk in patients with GHD. The present results suggest that GH plays a role in
      the regulation of fibrinolysis.

PMID- 8883282
TI  - A chimeric streptokinase with unexpected fibrinolytic selectivity.
AB  - Chimeric 59D8-SK was designed to confer fibrin-selectivity to streptokinase by
      fusion of the Fab fragment of anti-fibrin antibody 59D8 to the N-terminus of
      streptokinase (SK: Ile1-Lys414). It was expressed in a mouse hybridoma cell line
      and purified by affinity chromatography on a 59D8-antigen column. Chimeric 59D8
      SK is a disulfide-linked heterodimer composed of an antibody light chain (Mr
      27,000) and a N-glycosylated chimeric heavy chain (M(r) 90,000). The fibrin
      targeting by 59D8 increased plasma clot lysis by 2-fold, but connecting 59D8 to
      SK has provided 59D8-SK several unique properties: (i) 59D8-SK activated human
      Glu-plasminogen with a significant lag period that coincided with limited
      proteolysis of 59D8-SK similar to that observed for wild-type SK. In a kinetic
      study, both gave very similar kinetic parameters for the activation of Glu
      plasminogen even though 59D8-SK was N-glycosylated in its SK portion; (ii) 59D8
      SK was relatively inactive in human plasma, compared to SK, but it became
      activated in the presence of clots; (iii) 59D8-SK lysed clots slowly but
      completely whereas SK lysed clots rapidly but incompletely. Even though the
      mechanism behind these new properties is not fully understood, they are
      characteristics of a second-generation plasminogen activator.

PMID- 8883283
TI  - Ca(2+)-dependent activation of the 33-kDa protein kinase transmits thrombin
      receptor signals in human platelets.
AB  - Thrombin stimulation induces a dramatic increase in the activity of the 33-kDa
      serine/threonine kinase (PK33) in human platelets (10). The Arg-Gly-Asp (RGD)
      peptide, an inhibitor of the thrombin-mediated aggregation of platelets, did not
      affect the PK33 activation induced by thrombin suggesting that the activation of
      this kinase occurs independently from platelet aggregation. To identify a
      potential role of Ca2+ and calmodulin in the regulation of PK33, the effect of
      several Ca2+/calmodulin inhibitors on the thrombin-induced activation of PK33 was
      assessed using denaturation/renaturation method. Pretreatment of platelets with
      EGTA decreased the maximum PK33 activity induced by thrombin. The chelation of
      both the extra- and the intracellular Ca2+ by EGTA and by acetoxymethyl ester of
      5,5'-dimethyl-bis-(0-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM)
      decreased further the PK33 activation by thrombin. Preincubation of platelets
      with the anticalmodulin agent, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide
      (W13), inhibited markedly the activation of PK33 by thrombin, whereas the
      inactive structural analog N-(4-aminobutyl)-2-naphthalenesulfonamide (W12) and
      the myosin light chain kinase inhibitor 1-(5-chloronaphthalene-1-sulfonyl)-1H
      hexahydro-1,4-diazepine (ML9) showed very weak inhibitory effects. Treatment of
      resting platelets with the calcium ionophore, A23187, activated PK33 in a dose
      dependent manner; phorbol 12-myristate 13-acetate enhanced this effect. However,
      the two foregoing agents did not induce similar degree of PK33 activities as
      thrombin. These results indicate that the activation of PK33 is independent of
      the formation of the GPIIb/IIIa-fibrinogen complex and that it might be regulated
      by a Ca(2+)-dependent pathway.

PMID- 8883284
TI  - Agonist-induced actin polymerization is required for the irreversibility of
      platelet aggregation.
AB  - Cytochalasin D was used to investigate the role of intracellular cytoskeleton in
      the stabilization of platelet aggregation induced by strong platelet agonists.
      Incubation of gel-filtered platelets with increasing concentrations of
      cytochalasin D resulted in a dose-dependent inhibition of actin polymerization
      and association of actin-binding proteins with the Triton X-100-insoluble
      material induced by the thromboxane analogue, U46619, and the thrombin receptor
      activating peptide, TRAP. The same concentrations of cytochalasin D did not
      significantly inhibit platelet aggregation promoted by the two agonists. The
      addition of the chelating agent EDTA to fully aggregated platelets, that had been
      treated with cytochalasin D, resulted in the rapid and almost complete
      disaggregation. EDTA did not cause disaggregation of control, solvent-treated,
      aggregated platelets. The degree of platelet disaggregation induced by EDTA was
      dependent on the dose of cytochalasin D used, and was correlated with the
      inhibition of the cytoskeletal reorganization. Aggregation of cytochalasin D
      treated platelets stimulated with U46619 or TRAP was also reverted by the
      addition of the tetrapeptide RGDS or the fibrinogen gamma-chain dodecapeptide,
      which competitively interfere with fibrinogen binding to the glycoprotein IIb
      IIIa complex. These results indicate that the intracellular cytoskeleton plays an
      essential role in the stabilization of the fibrinogen-platelet interaction, and
      is necessary for the irreversibility of platelet aggregation induced by strong
      agonists.

PMID- 8883285
TI  - Antiplatelet activity in onion (Allium cepa) is sulfur dependent.
AB  - Plants of the genus Allium such as onion and garlic are often consumed as a
      source of compounds which inhibit human platelet activity, with the goal of
      decreasing vascular disease. Antiplatelet activity in these plants is determined
      in part by native concentrations of organosulfur compounds. Evaluation of four
      onion genotypes grown in a field study at four US locations in 1994 demonstrated
      onions with mild flavor and low sulfur content exhibited significantly lower
      antiplatelet activity than those containing high levels of sulfur. Antiplatelet
      activity was significantly positively correlated with genotypically determined
      bulb sulfur content and dissolved solids, indicating these latter factors are
      good predictors of antiplatelet strength. These data demonstrate antiplatelet
      activity is genotype dependent and correlated with bulb sulfur content. Genotype
      and bulb sulfur content should be taken into account in studies assessing onion
      antiplatelet effects.

PMID- 8883286
TI  - Characterization of recombinant von Willebrand factors mutated on cysteine 509 or
      695.
AB  - The interacting domain of vWF with platelet GPIb has been shown to overlap the
      large A1 loop formed by the intra-chain disulfide bond linking Cys 509 to Cys
      695. In order to further investigate the role of the conformation of this region,
      we have expressed in COS-7 cells three mutated full-length recombinant vWFs
      (rvWFs) in which the substitutions Cys509Gly, Cys509Arg or Cys695Gly have been
      introduced by site-directed mutagenesis. SDS-agarose gel electrophoresis
      demonstrated an impaired multimerization of the mutants with undetectable high
      molecular weight multimers and a decrease of the relative amounts of the
      intermediate sized multimers. Binding analysis showed that rvWFC509G and
      rvWFC509R did not interact with botrocetin but spontaneously interacted with
      GPIb; the latter binding remained unchanged in the presence of ristocetin. This
      indicates that the substitution of Cys509 by Gly or Arg creates a conformation of
      vWF that increases its binding to GPIb. In contrast, rvWFC695G which did not
      react with botrocetin was also unable to interact with GPIb even in the presence
      of ristocetin, indicating that sequences interacting with GPIb are masked and/or
      disrupted. In conclusion, the substitution of each of the Cys509 and 695 results
      in mutant proteins which may be "locked" into active or inactive conformations in
      regard to the binding to platelet GPIb receptor.

PMID- 8883287
TI  - Evaluation of the abnormal platelet function in von Willebrand disease by the
      blood filtration test.
AB  - We have evaluated platelet function in different subtypes of von Willebrand
      disease (vWD) by pushing blood through the capillary-sized channels of a glass
      filter. Patients, including those with type IIB vWD, showed lower than normal
      platelet retention and increased cumulative number of blood drops passing through
      the filter as a function of time. In contrast, shear-induced platelet
      aggregation, measured in the cone-and-plate viscometer, was paradoxically
      increased in type IIB patients. Treatment with 1-desamino-8-D-arginine
      vasopressin (DDAVP) tended to normalize the filter test in patients with type I
      platelet normal and type I-platelet low vWD, but infusion of a factor VIII/von
      Willebrand factor (vWF) concentrate lacking the largest vWF multimers was without
      effect in type 3 patients. Experiments with specific monoclonal antibodies
      demonstrated that the A1 and A3 domains of vWF, as well as the glycoproteins Ib
      alpha and IIb-IIIa on platelets, are required for platelet retention in the
      filter. Thus, the test may reflect vWF function with regard to both platelet
      adhesion and aggregation under high shear stress, and provide relevant
      information on mechanisms involved in primary hemostasis.

PMID- 8883288
TI  - Inhibitory effect of prostacyclin and nitroprusside on type IIB von Willebrand
      factor-promoted platelet activation.
AB  - Von Willebrand disease (vWD) of type IIB is a hereditary haemorrhagic disorder
      characterised by an excessive interaction of von Willebrand factor (vWF) with the
      platelet receptor GPIb which promotes platelet activation and aggregation through
      a phospholipase A2-mediated release of arachidonic acid. The present report shows
      that prostacyclin and nitroprusside, vasodilator-compounds that enhance the cAMP
      and cGMP concentration respectively, cause a drastic inhibition of the type IIB
      vWF-induced platelet responses including increase of cytosolic Ca2+
      concentration, phosphorylation of pleckstrin (47 kDa) and myosin light chain (20
      kDa), secretion of ATP and serotonin, and aggregation parallel to a decrease of
      arachidonic acid release. Type IIB vWF also elicits tyrosine phosphorylation of
      proteins with apparent molecular mass of 60, 74, 82 and 130 kDa. Prostacyclin,
      which induces per se tyrosine-phosphorylation of proteins of about 38 and 45 kDa,
      inhibits drastically the type IIB vWF-promoted tyrosine-phosphorylation of the 74
      kDa protein while inhibits slightly that of 60 kDa band. The protein tyrosine
      kinase inhibitor genistein causes a little decrease in the type IIB vWF-induced
      release of arachidonic acid. It is concluded that the inhibition exerted by
      prostacyclin and nitroprusside on type IIB vWF-elicited platelet activation seems
      to be largely ascribable to prevention of the phospholipase A2 activation with
      the ensuing decrease of the subsequent protein tyrosine phosphorylation.

PMID- 8883289
TI  - Plasminogen deficiency: an additional risk factor for thrombosis in a family with
      factor V R506Q mutation?

PMID- 8883290
TI  - No increased prevalence of the factor V Leiden mutation in chronic major vessel
      thromboembolic pulmonary hypertension (CTEPH)

PMID- 8883291
TI  - Oral contraceptives are a risk factor for cerebral vein thrombosis.

PMID- 8883292
TI  - Simplified procedure for thromboplastin calibration.

PMID- 8883293
TI  - A bioluminescent adenosine nucleotide release assay for the diagnosis of heparin
      induced thrombocytopenia.

PMID- 8883294
TI  - The presence of antibodies against a PF4-heparin complex in patients on
      haemodialysis.

PMID- 8883295
TI  - Ly-6-domain proteins--new insights and new members: a C-terminal Ly-6 domain in
      sperm acrosomal protein SP-10.

PMID- 8883296
TI  - Six newly identified HLA-DRB alleles: DRB1*1121, *1419, *1420, *1421, DRB3*0203
      and DRB5*0103.
AB  - Seven samples with irregular PCR-SSO hybridization patterns, observed during
      routine HLA-DRB typing, were studied in more detail. Group-specific
      amplification, followed by hybridization with relevant SSOs strengthened the
      suggestion that these samples contained new DRB alleles. DRB exon 2 segments were
      amplified, cloned and sequenced and revealed: DRB1*1121 [MUL] is similar to
      DRB1*1102 in which codon 85 changed from GTT(V) into GTC(A); DRB1*1419 [AKKAL] is
      similar to DRB1*1402 with codon 71 changed from AGG(R) into AAG(K); DRB1*1420
      [OND-52971] is a DRB1*1406 with codon 37 changed from AAC(N) into TTC(F);
      DRB1*1421 [TGI] is similar to DRB1*1417 with codon 71 changed from AGG(R) into
      AAG(K); DRB3*0203 [POS] is similar to DRB3*0202 in which codons 37-38 are changed
      from TAC GCG(YA) into TCC GTC(SV); DRB5*0103 was found in two unrelated
      individuals of Oriental origin [IND-24 and IND-59] and is similar to DRB5*0102 in
      which codon 71 AGG(R) changed into ACG(T). This particular sequence variation at
      position 71 has not yet been described. The new DRB sequences were confirmed
      using the sequencing based typing technique. Low resolution PCR-SSP typing failed
      to amplify two of the DRB1*14 variants, whereas high resolution PCR-SSP resulted
      in aberrant patterns. Class II alloantisera identify the codon 71 changes in
      DRB1*1419 and *1421 with respect to the MC1 ('DR1+DR4') epitope.

PMID- 8883297
TI  - Linkage disequilibrium between HLA class II (DR, DQ, DP) and antigen processing
      (LMP, TAP, DM) genes of the major histocompatibility complex.
AB  - TAP, LMP and DM genes map within the major histocompatibility complex (MHC) class
      II region between the DQB1 and DPB1 loci, and are involved in the processing of
      peptides bound to HLA class I or class II molecules. In order to determine the
      various linkage disequilibria existing between these genes and HLA class II
      genes, we have analyzed TAP1, TAP2, LMP2, DMA, DMB, DRB1, DQA1, DQB1 and DPB1
      polymorphisms in 162 unrelated healthy Caucasian individuals. Many positive or
      negative associations were observed between alleles at these loci, such as
      between DR/DQ and TAP2, DM or LMP, between DP and DMB, and between TAP2 and DM,
      TAP2 and LMP. Conversely, no linkage disequilibrium was detected between some
      closely related genes (DR/DQ and TAP1, TAP1 and TAP2, LMP2 and DM), in agreement
      with the existence of recombination hot spots in this region. Other weak linkage
      disequilibria are likely to exist in this region. These data allow to define some
      conserved MHC class II haplotypes including HLA class II and TAP, LMP and DM
      alleles. Furthermore, the knowledge of such linkage disequilibria is of
      outstanding importance in order to avoid misinterpretation of the data when
      studying MHC class II associations with autoimmune diseases.

PMID- 8883298
TI  - Frequency of platelet-specific alloantigens in a Danish population.
AB  - This study reports the first data on gene frequencies of platelet alloantigens
      HPA-1, HPA-2, HPA-3, HPA-4 and HPA-5 in a population of unrelated Danish blood
      donors using PCR-techniques. The observed gene frequencies fit the Hardy-Weinberg
      equilibrium, and the calculated phenotype frequencies are similar to those
      obtained in other Caucasian populations: HPA-1a and -1b occur in 96.6% and 30.3%
      of 557 unrelated respectively. HPA-2a and -2b in 99.4% and 15.9% of 163 tested,
      HPA-3a and -3b in 88.3% and 63.2% of 163 tested, HPA-4a and -4b in 100% and 0% of
      131 tested, and finally HPA-5a and -5b in 100% and 15.7% of 427 tested. It is a
      major technical improvement to use PCR techniques for genomic typing of HPA. Not
      only is it possible to perform HPA typings in severely thrombocytopenic patient
      and on amniotic fluid cells of the fetus of alloimmunized mothers, but it must be
      expected that accuracy of the HPA typing will increase considerably, as has been
      the case with genomic HLA class II typing. Finally, use of PCR technique combined
      with allele-specific primers is suitable for accurate large scale typing of
      platelet donors, which may be useful in special clinical settings.

PMID- 8883299
TI  - Sequence-specific priming and exonuclease-released fluorescence detection of HLA
      DQB1 alleles.
AB  - Molecular typing of HLA DQB1 alleles, employing sequence-specific primers (SSP)
      for PCR amplification, was used to test a novel method that eliminates the
      requirement for subsequent gel electrophoresis or additional hybridization steps
      by directly detecting positive reactions. We have evaluated the performance of
      this fluorescence-based oligonucleotide probe assay to assign the most common
      DQB1 alleles on DNA from 14 homozygous cell lines and in a blind study of 50
      diabetic patient samples that had been previously typed at the DQB1 locus using
      SSOP and conventional SSP-based approaches. We used a panel of 14 DQB1 SSP primer
      pairs, internal control primers, and a combination of 4 fluorescent
      oligonucleotide probes to detect 14 alleles or groups of alleles and controls. We
      can reliably detect single-base allelic differences, observe 100% concordance
      with the results obtained using both of the standard methods, and are able to
      further subtype several alleles that are not easily distinguished using SSOP
      (e.g. DQB1 *0401/0402 and DQB1 *0302/ 0303). Sequence-specific priming and
      exonuclease-released fluorescence (SSPERF) detection is technically simple and
      can be performed in less than 2 hours, including DNA extraction, PCR
      amplification, data analysis and allele identification. This method is
      particularly useful for the analysis of large numbers of samples, for which high
      throughput is critical and for which gel-based approaches are difficult to
      perform. This technique may also be useful for small-scale class I and class II
      molecular typing in clinically oriented laboratories.

PMID- 8883300
TI  - HLA-C typing of eleven Papua New Guineans: identification of an HLA-Cw4/Cw2
      hybrid allele.
AB  - HLA-C polymorphism of 11 individuals from Papua New Guinea was studied by
      serology and DNA typing (SSP ARMS-PCR). To resolve certain discrepancies HLA-C
      alleles were cloned and sequenced. Five alleles were identified by sequencing,
      four of which; Cw*0304, Cw*0401, Cw*12022 and Cw*1502 have been identified
      previously in other populations. The fifth allele, which was found in four
      individuals is a novel HLA-C allele. The new allele, called HLA-Cw*0403 is most
      similar to HLA-Cw*0401, differing by 10 nucleotides, 9 of which are located in
      the region from nucleotide 98 to 218. This region of Cw*0403 is identical to both
      HLA-Cw*0201 and Cw*02022. The 9 nucleotide differences between Cw*0401 and
      Cw*0403 result in 6 amino acid differences in the alpha 1 domain. These amino
      acids in Cw*0403 may contribute to the serological typing of some, but not all
      Cw*0403 expressing cells. The Final difference between Cw*0401 and Cw*0403 is a
      coding substitution at nucleotide 979 in exon 5. The guanine found in Cw*0403 is
      identical to all HLA-C alleles except HLA-Cw*0401, which has an adenine. The
      Cw*0403 allele was most likely formed by a gene conversion event between Cw*02
      and Cw*04, involving a minimum of 121 to a maximum of 215 nucleotides.

PMID- 8883302
TI  - Apoptosis following interleukin-2 withdrawal from T cells: evidence for a
      regulatory role of CD18 (beta 2-integrin) molecules.
AB  - Following a successful immune response against invading microorganisms, the
      majority of activated T cells is eliminated, while a minor fraction survives as
      memory T cells. A decline in T lymphocyte growth factors such as interleukin-2
      (IL-2) appears to play a role in the elimination of previously activated T cells.
      Thus, removal of IL-2 from proliferating T cells not only induces growth arrest,
      but triggers a massive cell death due to apoptosis. While the apoptotic response
      involves a series of well-described events, it remains less clear how apoptosis
      is regulated following IL-2 withdrawal. Here, we provide evidence that CD18
      molecules (beta 2-integrins) play a regulatory role in the apoptotic response
      following removal of IL-2 from previously activated, antigen specific CD4+ T cell
      lines. Thus, CD18 mAb inhibited the apoptotic response to IL-2 deprivation,
      whereas mAb against other adhesion molecules (CD28, CD29, CD49d, CD80, CD86) did
      not. Secondly, IL-2 withdrawal resulted in a retarded apoptotic response in LFA-1
      (CD11a/CD18) negative T cells obtained from a leukocyte adhesion deficiency (LAD)
      patient, as compared to LFA-1 positive T cell lines. Thirdly, co-culture of LFA-1
      positive- and negative-T cells at different ratios induced apoptotic responses
      that were higher than expected, had the two lymphocyte populations not been
      interacting and significantly higher than that seen in pure LFA-1 negative T
      cells. Supernatants from LFA-1 positive T cell cultures undergoing apoptosis did
      not induce an enhanced apoptotic responses in LFA-1 negative T cells, and,
      reversely, culture supernatants from LFA-1 negative T cells did not rescue LFA-1
      positive cells from undergoing apoptosis. The apoptotic response was partly
      blocked by IL-15, a newly identified T cell growth factor. Taken together, these
      findings suggest that CD18 molecules (beta 2-integrins) play a regulatory role in
      the apoptotic response following cytokine withdrawal, and that the regulation is
      mediated, at least partly, through T-T cell interactions. Thus, apoptotic death
      following IL-2 deprivation appears to be under "social" control by surrounding T
      cells.

PMID- 8883301
TI  - Six new DR52-associated DRB1 alleles, three of DR8, two of DR11, and one of DR6,
      reflect a variety of mechanisms which generate polymorphism in the MHC.
AB  - We have sequenced DNA from six new DR52-associated DRB1 alleles initially
      detected by PCR/SSOP analysis. Three DR8 associated alleles differed from
      previously known alleles by single nucleotide substitutions. DRB1*0807 and
      DRB1*0811 both vary from DRB1*08021 at codon 57 resulting in two different amino
      acids at this residue. DRB1*0807 was identified in samples of Brazilian origin
      while *0811 was identified among samples from the Tlingit Native American
      population of Southeast Alaska. DRB1*0814, identified in a family of Chinese
      origin, differed from DRB1*08032 at codon 12 at both the nucleotide and the amino
      acid level. In addition, two alleles of DR11, DRB1*1113 and *1119, were each
      detected in Caucasian individuals. DRB1*1113 differs from other DR11 alleles at
      codons 37, 67, 70 and 74, while DRB1*1119 differs from *1101 by a single
      nucleotide substitution at codon 67. Finally, DRB1*1418 was detected in a sample
      from an Asian or Pacific Islander and shares sequences with several other DR52
      associated DRB1 alleles. These six DRB1 alleles appear to have been generated by
      either gene conversion events, DRB1*1113 and *1418, or by point mutations,
      DRB1*0814, *0807, *0811 and *1119, although the single nucleotide substitutions
      found in the latter three alleles are also present in at least one other DRB1
      allele and, therefore, could have been the product of gene conversions.

PMID- 8883303
TI  - Possible HLA association with susceptibility to HTLV-1 tropical spastic
      paraparesis in Israel in Iranian Jews as compared to HTLV 1-associated myelopathy
      in Japan.

PMID- 8883304
TI  - Nucleotide sequence of the corrected DQB1*06011 allele.

PMID- 8883305
TI  - Nomenclature for factors of the HLA system, update May 1996. WHO Nomenclature
      Committee for Factors of the HLA system.

PMID- 8883306
TI  - Intervillous circulation in the first trimester: the phantom of the color Doppler
      obstetric opera.

PMID- 8883307
TI  - Assessment of the fetal circulatory state in uteroplacental insufficiency by
      Doppler ultrasound: which vessels are the most practicable?

PMID- 8883308
TI  - Adrenal artery velocity waveforms in the appropriate and small-for-gestational
      age fetus.
AB  - The purpose of this study was to compare adrenal artery flow velocity waveforms
      in the appropriately grown and the small-for-gestational-age fetus. Adrenal
      artery flow velocity waveforms were prospectively obtained from 131 appropriate-
      and 21 small-for-gestational-age fetuses with pulsed Doppler ultrasonography. The
      success rate in recording the adrenal artery was 84% (131/155) and 100% in the
      appropriate- and small-for-gestational-age fetuses, respectively. The pulsatility
      index (PI) was used to quantify the waveforms. The PI in the appropriate-for
      gestational-age fetuses decreased linearly with gestational age (PI = 1.7-0.016 x
      gestational age). In ten small-for-gestational-age fetuses the adrenal artery PI
      was below the 95% confidence interval. Small-for-gestational-age fetuses with
      abnormal adrenal artery PI had a significantly higher incidence of fetal heart
      rate decelerations, preterm delivery and Cesarean sections when compared to small
      for-gestational-age fetuses with normal adrenal artery PI. Our data indicate that
      the PI of the adrenal artery in the normal fetus decreases with advancing
      gestation, and they suggest that in the small-for-gestational-age fetus there is
      an increased blood flow to the adrenal gland. We postulate that management of the
      small-for-gestational-age fetus may be aided by the study of the adrenal artery
      flow velocity waveforms.

PMID- 8883309
TI  - Blood flow velocity waveforms from peripheral pulmonary arteries in normally
      grown and growth-retarded fetuses.
AB  - The objective of this study was to describe blood flow velocity waveforms of
      fetal peripheral pulmonary arteries in normally grown and growth-retarded
      fetuses. Doppler studies were performed in 182 normally grown fetuses
      (gestational age 18-40 weeks) and in 61 growth-retarded fetuses (gestational age
      24-36 weeks) that were free from structural and chromosomal abnormalities and
      whose umbilical and middle cerebral artery Doppler findings suggested
      uteroplacental insufficiency as the most likely etiology of the growth defect.
      The pulsatility index was used to quantify the velocity waveforms. Successful
      recordings were obtained in 90.1% of the normally grown and 93.4% of the growth
      retarded fetuses. In normally grown fetuses the pulsatility index values
      significantly decreased with advancing gestation. In growth-retarded fetuses the
      pulsatility index values were significantly elevated compared to those of normal
      fetuses. A significant relationship was observed between the severity of hypoxia
      and pulsatility index values from the peripheral pulmonary arteries in 29 fetuses
      in which Doppler recordings were obtained immediately before cordocentesis. In
      conclusion, these data show that in normal fetuses the Doppler-measured impedance
      to flow in the peripheral pulmonary circulation decreases with advancing
      gestation. Impedance to flow in the lungs is elevated in the presence of growth
      retardation and this increase is related to the severity of fetal hypoxia.

PMID- 8883310
TI  - Venous circulation in the maternal lower limb: a Doppler study with the Valsalva
      maneuver.
AB  - In order to evaluate the normal physiology of the maternal venous circulation,
      Doppler examinations of the venous system in the right inferior extremity and
      suprainguinal part of the common femoral vein were carried out in 38 healthy
      pregnant women, in 12 non-pregnant controls and in 16 women at early puerperium.
      Examinations were carried out when the mother was lying in a left semi-recumbent
      supine position. Blood flow velocities in the suprainguinal femoral and deep
      femoral veins decreased significantly in the first trimester and were almost
      normalized by the third postpartum day. Continuous forward venous flow with
      respiratory fluctuation was maintained in the femoral veins over the whole
      gestational period. The response to the Valsalva maneuver was similar in the
      pregnant and non-pregnant women. Our findings provide evidence that the venous
      valvular system and wall distensibility in the femoral area and the inferior
      extremity are in vivo not greatly changed in pregnancy. A more important reason
      for decreased velocities is probably the pregnancy-associated decrease of the
      arterial input to this area.

PMID- 8883311
TI  - Uterine arcuate artery Doppler and decidual microvascular pathology in
      pregnancies complicated by type I diabetes mellitus.
AB  - The objective was to correlate Doppler indices from the uterine arcuate arteries
      with an analysis of the decidual vascular histology in patients with type I
      diabetes. Pulsed wave Doppler was used to sample the uterine arcuate artery
      system beneath the placenta within 8 days of delivery in 47 patients with type I
      diabetes mellitus. A placental pathologist, without knowledge of either clinical
      outcome or Doppler information, classified the histological appearance of the
      decidual arteries as normal, type A (hyalinization, mural thickening), or type B
      (fibrinoid necrosis, atherosis, thrombosis). Patients were then grouped according
      to the histology of the decidual arteries. An analysis of variance (ANOVA) of the
      systolic/diastolic (S/D) ratios (log. S/D) showed significant variation (p <
      0.025). A multiple range comparison test showed that patients with normal or only
      mildly abnormal (type A) vessels had similar values, whereas those with severe
      vasculopathy (type B) had significantly higher S/D ratios (p < 0.05). The study
      confirmed a relationship between arcuate artery Doppler indices and downstream
      decidual vascular pathology.

PMID- 8883312
TI  - Autosomal dominant cataracts of the fetus: early detection by transvaginal
      ultrasound.
AB  - Cataracts are lens opacities that account for approximately 10% of blindness in
      children. We report on four consecutive pregnancies in a woman at risk for
      recurrent autosomal dominant cataracts in which extensive ultrasound studies were
      helpful in establishing the correct diagnosis. The normal appearance of the fetal
      lens is that of a ring with a central sonolucency, but in cases of cataracts the
      lens appears hyperechogenic to various degrees. In the first pregnancy, normal
      lenses were seen at 15 postmenstrual weeks and, at birth, the baby girl had
      normal lenses. In the second pregnancy, the male fetus was affected by a left
      sided cataract and a right-sided anophthalmia which were diagnosed at 16
      postmenstrual weeks. The histological examination of the specimen from the
      aborted fetus correlated with the sonographic diagnosis. The third pregnancy,
      also a male fetus, had bilateral cataracts suspected at 14 weeks, but the final
      diagnosis was made at 19 weeks and confirmed at 21 weeks. The couple opted to
      terminate the pregnancy and the histology confirmed the presence of congenital
      cataracts. In the fourth pregnancy, we diagnosed asymmetry of the orbital sizes
      and bilateral cataracts at 15 weeks. In conclusion, the diagnosis of fetal
      cataract from the second trimester of pregnancy is possible and imaging of the
      fetal lenses should be part of the routine anatomical survey. Since the exact
      onset of fetal cataracts is uncertain at present, in cases at risk, serial
      sonograms may be indicated.

PMID- 8883313
TI  - Patterns of perinasal fluid flow and contractions of the diaphragm in the human
      fetus.
AB  - Our aim was to identify patterns of fetal perinasal fluid flow, and to determine
      the relationship of pattern of flow to the diaphragmatic component of fetal
      breathing movements. Twenty-four fetuses were studied with the use of two
      ultrasound systems simultaneously. Continuous video-tape records of the color and
      spectral Doppler imaging of fluid flow velocity in the nose and of the movements
      of the fetal diaphragm were made on two video recorders during 30-min study
      sessions. Two different patterns of fetal perinasal flow were recognized. One
      type had a rapid rate and low amplitude, and was independent of
      ultrasonographically observed movements of the fetal diaphragm. The other type
      had a lower rate and higher amplitude, and was uniformly related to diaphragmatic
      contractions. The breath-to-breath interval, time of inspiration, time of
      expiration and peak inspiratory and expiratory velocities were determined for
      each type of perinasal flow. Two ratios were used to quantify the change of peak
      flow velocity. There were significant differences in the values of all timing
      parameters between diaphragm-related perinasal flow velocities and those not
      related to the diaphragm, at both 30-36 and 37-41 weeks of gestation. The rate of
      perinasal flow related to diaphragmatic contraction cycles was one-third that of
      the flow cycles not related to diaphragmatic contraction (approximately 50 vs.
      148 cycles/min). For both patterns of perinasal flow velocity, the expiratory
      peak velocity ratio was about 1.6 times higher than the inspiratory peak velocity
      ratio. We conclude that, in uncomplicated pregnancy, one pattern of fetal
      perinasal fluid flow reflects activity of the diaphragm. We speculate that the
      contractions of the fetal airway smooth muscle or oropharyngeal-laryngeal muscle
      groups are the origin of the second pattern of perinasal flow.

PMID- 8883314
TI  - Transvaginal color Doppler sonography in adnexal masses: which parameter performs
      best?
AB  - The aim of this study was to establish which of several commonly used parameters
      performs best in the evaluation of adnexal masses by transvaginal color Doppler
      sonography. A total of 79 adnexal masses in 73 consecutive patients were included
      in the study. There were 43 (58.9%) premenopausal and 30 (41.1%) postmenopausal
      patients. The median age was 45 years (range 20-78 years). The parameters
      compared were: number of vessels detected in each tumor, tumor vessel location
      (central vs. peripheral), peak systolic velocity (PSV), lowest resistance index
      (RIlowest), mean resistance index (RImean), lowest pulsatility index (PIlowest)
      and mean pulsatility index (PImean). Receiver operating characteristic (ROC)
      curves were plotted to analyze the test performance of the parameters, except for
      tumor vessel location, and to estimate the best cut-off value of the parameters
      studied to differentiate between malignant and benign tumors. Definitive
      histopathological diagnosis was obtained in every case and used as the 'gold
      standard'. There were 20 (25.3%) malignant and 59 (74.7%) benign masses. Color
      Doppler signals were detected in 100% of the malignant masses (20 out of 20) and
      74.6% (44 out of 59) of the benign masses, and the difference was found to be
      statistically significant (p < 0.001). Tumor vessel location was central in 18
      out of 20 (90%) malignant masses, whereas it was peripheral in 39 out of 44
      (88.6%) benign masses. ROC analysis showed that the best cut-off values for
      number of vessels, PSV, RIlowest, RImean, PIlowest and PImean were three vessels,
      25 cm/s, 0.45, 0.55, 0.90 and 1.50, respectively. However, for all these
      parameters except RIlowest, there was a considerable overlap between benign and
      malignant tumors, with a high false-positive rate. In conclusion, in our
      experience, the parameters that performed best were the RIlowest with a cut-off
      value of 0.45 (sensitivity 100%; false-positive rate 11.4%) and central tumor
      vessel location (sensitivity 90%; false-positive rate 11.4%).

PMID- 8883315
TI  - Multiple intracardiac tumors: spontaneous prenatal recovery of fetal
      bradyarrhythmia.
AB  - Although prenatally detected intracardiac tumors are reported to have a poor
      prognosis, tumor regression and even tumor disappearance have been observed
      during childhood. A case of prenatal cessation of fetal cardiac tumor growth and
      return of cardiac arrhythmia to normal sinus rhythm is presented.

PMID- 8883316
TI  - Prenatal diagnosis of amniotic band syndrome in a methadone user: review of the
      literature and a case report.
AB  - We present a case and review of the literature of an amniotic band causing
      malformation in the distal forearm in a baby born to a methadone-dependent
      mother. This diagnosis was made prenatally at the routine 18-20-week gestation
      anomaly ultrasound scan. Histology of the amniotic band postpartum revealed hair
      shafts within its structure. This has not previously been documented, nor has an
      association of this syndrome with systematic abuse of methadone. The fact that
      this anomaly could be detected by prenatal ultrasound scanning is of value in the
      counselling of high-risk pregnancies such as this.

PMID- 8883317
TI  - Prenatal diagnosis of bilateral proximal femoral hypoplasia.
AB  - Proximal femoral focal deficiency is a rare skeletal disorder, with an estimated
      incidence of 0.11 to 0.2/10,000 births. The bilateral form is uncommon, occurring
      in 10 to 15% of cases. We report a case of bilateral proximal femoral focal
      deficiency diagnosed by ultrasound at 30 weeks' gestation. Differential
      diagnosis, prognosis and management are discussed.

PMID- 8883318
TI  - Antenatal sonographic findings associated with scimitar syndrome.
AB  - Scimitar syndrome is a rare congenital anomaly that consists of secondary
      dextroposition in situs solitus, due to right pulmonary hypoplasia. The prenatal
      sonographic findings of this abnormality have not been previously described. We
      describe early sonographic findings in a fetus that included isolated cardiac
      dextroposition with normal abdominal situs, hydramnios and mild narrowing of the
      right pulmonary artery. Postnatally, the infant developed heart failure, and a
      right hypoplastic lung was found. Catheterization revealed collateral supply to
      the right lung arising from the descending aorta and anomalous drainage of right
      pulmonary veins to the inferior vena cava. The diagnosis of scimitar syndrome was
      therefore established. A coil embolization of arterial collaterals to the right
      lung was performed. Scimitar syndrome should be considered in a fetus with the
      sonographic findings of a right shift of the mediastinal structures, an intact
      diaphragm and narrow right pulmonary artery. This may allow early neonatal
      stabilization and treatment.

PMID- 8883319
TI  - Ultrasound-guided hysteroscopic management of endometrial osseous metaplasia.
AB  - In the past, most cases of osseous metaplasia of the endometrium were diagnosed
      following removal of bone from the endometrium by dilatation and curettage and
      frequently subsequently treated by hysterectomy. Nowadays, management involves a
      suggested diagnosis by transvaginal ultrasound examination, confirmation by
      hysteroscopy and hysteroscopic removal of ectopic intrauterine bone. This is
      usually carried out under laparoscopic guidance. However, the degree of visual
      control provided by combined transabdominal and transrectal ultrasonography may
      prove sufficiently accurate for hysteroscopic guidance. In this report we
      describe a case of endometrial osseous metaplasia successfully managed by
      ultrasound-guided hysteroscopy. The advantages of our approach include reduced
      invasiveness, reduced costs and simultaneous visualization of the abdominal and
      intrauterine cavities. One limitation, however, is represented by the greater
      operator dependence of ultrasound guidance as compared to laparoscopy, the former
      requiring extensive training and state-of-the-art equipment. We suggest that
      ultrasound guidance for hysteroscopic removal of extensive osseous metaplasia may
      represent a potentially safer and more effective alternative to laparoscopy and
      would therefore encourage further clinical evaluation of this technique.

PMID- 8883320
TI  - A different option for transvaginal color Doppler imaging: the diagnosis of
      pelvic varicosities.

PMID- 8883321
TI  - Screening for nuchal translucency: expect or expedite?

PMID- 8883322
TI  - Prenatal diagnosis of vasa previa with transvaginal color Doppler ultrasound.

PMID- 8883323
TI  - Orientation of the fetus.

PMID- 8883324
TI  - High-resolution ultrastructural study of the rat glomerular basement membrane in
      aminonucleoside nephrosis.
AB  - In the initial stages of aminonucleoside nephrosis, functional alterations in the
      glomerular basement membrane occur, as evidenced by the development of
      proteinuria. However, it has not been possible to observe important
      ultrastructural modifications at the level of the basement membrane, probably
      because the changes are taking place at the molecular level. In this study, by
      the use of high-resolution electron microscopy, an attempt was made to evaluate
      such changes in rat glomerular basement membrane during acute aminonucleoside
      nephrosis. As previously reported, in control animals the glomerular basement
      membrane is composed of a network of 4-nm-wide irregular anastomosing strands,
      referred to as "cords," which are known to contain a core filament of type IV
      collagen surrounded by a "sheath" of other components, such as laminin and
      heparan sulfate proteoglycan (HSPG). The most conspicuous ultrastructural
      alteration of the nephrotic glomerular basement membrane, recognizable only at
      high magnification, is that the cords were denuded leaving only the core filament
      through the loss of the sheath material. Thus, the cord network was transformed,
      with the progress of pathological conditions, into a network of fine filaments.
      On the other hand, abundance and distribution of HSPG molecules known to be
      present in the form of 4.5- to 5-nm-wide ribbon-like "double tracks," were found
      to be similar in control and nephrotic tissues. Since HSPG is one of the charge
      proteins of the basement membrane, the little changes observed for HSPG are
      difficult to interpret in view of reported decreases in basement membrane anionic
      sites in nephrosis. In conclusion, the glomerular basement membrane in
      aminonucleoside nephrosis loses its cord network components and replaces them
      with a more perforated network, which could be a cause for the increased
      permeability of this basement membrane.

PMID- 8883325
TI  - Ultrastructure of cellular congenital mesoblastic nephroma.
AB  - A detailed ultrastructural description of the cellular variant of congenital
      mesoblastic nephroma (CMN) is presented and compared to the classical form.
      Studied were 9 cases of the cellular variant, 6 mixed (cellular/classical)
      tumors, and 1 classical CMN. The occurrence of a broad selection of
      ultrastructural features was assessed using a semiquantitative scoring system.
      The results indicate that cellular CMNs are composed mainly of primitive
      mesenchymal cells, but also usually contain varying numbers of differentiating
      fibroblasts and myofibroblasts. This entity thus bears a closer resemblance at
      the ultrastructural level of organization to infantile fibrosarcoma than to
      conventional fibrosarcoma. Electron microscopy can be useful in distinguishing
      this relatively benign entity from the several malignancies with which it is
      sometimes confused.

PMID- 8883326
TI  - Disseminated blastomycosis and acquired immunodeficiency syndrome: a case report
      and ultrastructural study.
AB  - A 42-year-old, African-American man presented with a 2-month history of weight
      loss and fever for 2 weeks. Presumptive diagnoses of human immunodeficiency virus
      infection (HIV) and acquired immunodeficiency syndrome were made on the basis of
      a CD4 lymphocyte count of 23 lymphocytes/mL. Chest x-ray revealed right
      paratracheal adenopathy and a miliary pattern. The etiology of the patient's
      pulmonary infection was not known, but tuberculosis was an important
      consideration. Over 5 days, the pulmonary infection progressed and was
      complicated by acute respiratory distress syndrome (ARDS), septic shock, and
      death, despite vigorous antibiotic and supportive therapy. Serologic tests for
      HIV infection were reported as positive after the patient's demise. The etiology
      of the patient's pulmonary infection, ARDS, and sepsis was not known until
      autopsy study revealed enumerable yeast-like cells of Blastomyces dermatitidis in
      the extensively consolidated lungs and in disseminated foci of infection in most
      other major organs. Diffuse alveolar damage was closely associated with the
      pulmonary blastomycosis. Electron microscopic study of the yeast-like cells of B.
      dermatitidis in the autopsy lung obtained and fixed 5 days after the patient's
      death revealed excellent preservation of viable organisms.

PMID- 8883327
TI  - Myelin-containing corpora amylacea in vestibular root entry zone.
AB  - The vestibular nerve of patients with Meniere's disease and vascular cross
      compression syndrome of the root entry zone due to the antero-inferior cerebellar
      artery was studied. All patients underwent vestibular neurectomy using the
      retrosigmoid approach, which permits the removal of a long nerve segment. CA were
      found in the cytoplasm of astrocytes that had not shown signs of degeneration at
      the central portion of the vestibular root entry zone. No membrane intervened
      between CA and the surrounding cytoplasm, which was rich in filaments, in
      particular near the CA, and poorly equipped with other organelles. CA were round
      or oval inclusions measuring 10-12 microns in diameter. The matrix of the CA was
      composed of low-density amorphous material, with irregular masses displaying a
      medium density. A network of randomly oriented filaments and bilaminar,
      osmiophilic lipid fragments with the same structure and thickness of myelin
      layers were embedded in the matrix. The CA rich in bilaminar fragments were
      recognizable also at low magnification for their high electron density. In the
      astrocytic cytoplasm, near the CA, round or ovalshaped, electron-dense bodies
      with a multilamellar structure were often visible. These results confirm the
      hypothesis that CA may contain degenerating myelin embedded in a microenvironment
      rich in glucose polymers and that CA could be an indicator of neurodegeneration.

PMID- 8883328
TI  - Helioid inclusions in dedifferentiated acinic cell carcinoma of the parotid
      gland.
AB  - Helioid bodies are exceedingly rare, intranuclear, rounded inclusions with
      peripheral radiating filaments. These structures, which were formerly observed in
      only three cases of proliferative breast epithelial lesions, appeared in 0.5-1%
      of the neoplastic cells of a case of dedifferentiated acinic cell carcinoma of
      the parotid gland. Helioid bodies are related to rough endoplasmic reticulum
      cisternae, which suggests that they are the result of the condensation and
      partial crystallization of their contents when sequestrated into the nuclear
      compartment of the cell. The presence of helioid bodies may be related to
      secretory dysfunction of the tumor cells associated with the process of
      neoplastic dedifferentiation.

PMID- 8883330
TI  - Programmed cell death of peripheral myeloid precursor cells in Down patients:
      effect of zinc therapy.
AB  - Hemopoietic stem cell differentiation represents the primary rule of self
      renewal, proliferation, and specialization modulated by several mechanisms,
      including growth factors, cell interactions, and bioavailability of various ions,
      especially Ca2+ and Zn2+. Apoptotic death, during normal cell turnover, has been
      widely studied and is recognized as an important pathway for clonal deletion in
      the hemopoietic system. Multiparametric analyses have shown that subjects with
      Down syndrome show low levels of plasmic zinc associated with the presence of
      immature myeloid cells in the peripheral blood. This arrangement is repaired by
      in vivo zinc therapy. This study presents morphological and biochemical analyses
      to show that ZnSO4 therapy induces the disappearance of peripheral myeloid
      precursor cells by a programmed cell death mechanism. The programmed zinc-therapy
      induced cell death presumably provides a simple way to regulate the myeloid
      differentiation selecting appropriate cells.

PMID- 8883329
TI  - Atypical glomus tumor in the mediastinum: a case report with immunohistochemical
      and ultrastructural studies.
AB  - A case is reported of atypical glomus tumor occurring in the posterior inferior
      mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was
      composed of atypical small, round tumor cells with scattered mitotic figures. In
      addition to sheet-like, diffuse proliferation of the tumor cells, some areas of
      the tumor contained small "glomoid" cells arranged in organoid and
      hemangiopericytomalike patterns. Immunohistochemically, many tumor cells were
      positive for muscle-type actins and a few cells were focally positive for desmin.
      Ultrastructural studies revealed smooth muscle features of tumor cells, that is,
      pinocytotic vesicles, external laminas, dense plaques, and occasional thin
      filaments with dense bodies. The patient remained well for 5 years and 4 months
      after the operation without additional radiation and chemotherapy. The tumor was
      diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically.
      It seems important to recognize the presence of this type of tumor in sites other
      than extremities and to differentiate it from other malignant small, round cell
      tumors.

PMID- 8883331
TI  - Lectin binding and uptake in human (myelo)monocytic cell lines: HL60 and U937.
AB  - The terminal carbohydrate residues of the human (myelo) monocytic cell lines HL60
      and two subclones of U937 were investigated by the use of lectins. Several
      terminal carbohydrate residues, including N-acetylglucosamine and carbohydrates
      of the complex type, were detected on all three cell lines. Except for galactose
      residues, the two subclones of U937 had almost identical terminal carbohydrate
      residues. The differences between the two U937 subclones and HL60 were more
      pronounced, the latter expressing fucose residues, which might be part of the
      CD15 cell adhesion molecules. Some of the differences of the carbohydrate
      residues between the cell lines could be attributed to their differentiation
      within the myelomonocytic cell lineage. Lectins that bound to the cell surface
      were internalized via either clathrin-coated pits and vesicles or nonspecific
      endocytosis, indicating that functionally different classes of cell surface
      glycoproteins are involved in lectin binding and internalization.

PMID- 8883332
TI  - Pearson's syndrome presenting with Fanconi syndrome.
AB  - A case of Pearson's marrow-pancreas syndrome is presented. The dominant clinical
      feature was a generalized disorder of proximal tubule function with severe renal
      magnesium wasting. Renal and muscle biopsies were performed and showed bizarre
      giant mitochondria.

PMID- 8883333
TI  - The liver in transforming growth factor-Beta-1 (TGF-beta 1) null mutant mice.
AB  - Transforming growth factor-beta-1 (TGF-beta 1) null mutant mice have no gross
      developmental abnormalities at birth but succumb to multifocal inflammatory
      lesions that lead to organ failure and death about 20 days after birth. Treatment
      with anti-inflammatory and immune suppressive agents, such as rapamycin, reduces
      the severity and extent of inflammatory infiltrates in the liver and can prolong
      the life of knockout (KO) mice compared to untreated null mice. To determine
      whether there is an associated hepatic phenotype, livers of "young" (< 3 weeks),
      "old" (> 3 weeks), and age-matched wild-type (WT) mice were studied using light
      and electronmicroscopy. On light microscopy, old KO mice had foci of mononuclear
      cells in liver parenchyma in addition to scattered foci of megalocytosis.
      Intracytoplasmic vacuoles, some of which were juxtanuclear in location, were also
      seen but these were most prominent in the oldest (10 weeks) rapamycin-treated
      mouse. In the untreated young KO mice, there were only foci of mononuclear cells
      in the liver parenchyma and portal tracts and variable numbers of binucleated
      hepatocytes. Ultrastructurally, there was a significant increase in the number of
      mitochondria in livers of the old KO mice, when compared either to the age
      matched wild-type or to the young KO mice (p > .001). Hepatocytes from all KO
      mice showed increased numbers of hypertrophied or enlarged Golgi complexes
      compared to age-matched wild-type mice. Intracytoplasmic canaliculi lined with
      microvilli were seen in livers of old KO mice, but were absent in the young KO
      and wild-type mice. Primary cultures of hepatocytes, derived from livers of both
      young and old KO mice, showed similar changes on phase contrast and
      electronmicroscopy. These included juxtanuclear vacuoles, intracytoplasmic
      canaliculi, enlarged Golgi vesicles, and increased numbers of autolysosomes.
      Phenotypic abnormalities of mitochondria were either minimal or absent in
      cultured KO hepatocytes. The findings demonstrate, for the first time, that
      targeted disruption of the TGF-beta 1 gene in mice results in an altered
      ultrastructural phenotype of hepatocytes. The data suggest that TGF-beta 1 may be
      required for normal development and regulation of subcellular organelles in
      hepatocytes and may be essential for physiological functions involving
      mitochondria and Golgi complex.

PMID- 8883334
TI  - Ultrastructural features of danazol-induced cholestasis: a case study.
AB  - A case study of a severe cholestatic syndrome induced by danazol, with
      ultrastructural description of liver morphology, is reported. Cholestasis
      appeared after 3 months treatment with danazol (300 mg/daily) and completely
      resolved 2 months after withdrawal. In spite of the severe increase in serum
      bilirubin and total serum bile salts, transaminases were only slightly elevated
      and GGT and alkaline phosphatases were almost normal. Light microscopy shows a
      pattern of predominantly centrolobular cholestasis without necrosis, with minimal
      inflammatory infiltrate and with no sign of bile ductule involvement. At the
      ultrastructural level very dilated bile canaliculus predominate with stunted or
      loss of microvilli and dense bile material in the lumen. Nonspecific alterations
      were seen in hepatocyte intracellular organelles. It is suggested that danazol
      may cause a rare but severe hepatocanalicular cholestasis, differing from the
      "bland" cholestasis frequently described during therapy with other anabolic
      steroids.

PMID- 8883335
TI  - Incidence of clinical mastitis in a random sample of dairy herds in the southern
      Netherlands.
AB  - The incidence of clinical mastitis and distribution of pathogens in dairy cows
      was estimated in 171 randomly selected dairy herds in the southern Netherlands. A
      total of 1103 quarter cases were reported. The average annual incidence rate was
      12.7 quarter cases per 100 cows per year. The most frequent isolates from
      clinical cases were Escherichia coli (16.9 per cent), Staphylococcus aureus (14.4
      per cent), Streptococcus uberis (11.9 per cent) and Streptococcus dysgalactiae
      (8.9 per cent). Most cases were reported in early lactation: 25.4 per cent in the
      first month of lactation for all cows, and 39.1 per cent in the first month for
      first lactation cows. The rear quarters had a significantly higher incidence rate
      than the front quarters. Cows with an E coli infection showed more general
      clinical signs than cows infected with S aureus, S uberis and S dysgalactiae. A
      significantly higher incidence was observed in herds with a low (< 150,000
      cells/ml) bulk milk somatic cell count than in herds with a count above 250,000
      cells/ml.

PMID- 8883336
TI  - Development of frozen-thawed porcine blastocysts in vitro and in vivo.
AB  - Cryopreservation of porcine embryos would greatly facilitate the maintenance of
      genetic resources and the practical application of embryo transfer programmes. In
      this study, the effect of the stage of development of porcine embryos (prehatch
      vs post hatch) on the post thaw viability of blastocysts was evaluated. The
      blastocysts had been recovered from superovulated donor gilts and frozen in 1.5M
      glycerol according to a standard slow cooling protocol. From 444 frozenthawed
      embryos, 302 (68 per cent) were judged to be viable and were used for a 24-hour
      culture experiment in modified Whitten's medium (n = 89) or transferred to three
      synchronous (n = 72) or seven asynchronous (-24 hours) recipients (n = 141). The
      proportion of embryos surviving in culture was significantly (P = 0.05) greater
      for those frozen as post hatch (17/34) than as pre-hatch blastocysts (8/36).
      Although transfer of frozen-thawed embryos to synchronous recipients did not
      result in a pregnancy, two of the asynchronous recipients, which received 15 and
      22 embryos, became pregnant and farrowed five and three piglets, respectively, at
      normal term. In spite of the overall inefficiency of the cryopreservation
      procedure used in this study, the birth of piglets from two successful transfers
      of frozen-thawed blastocysts suggests that further study of the cryopreservation
      protocols would be worthwhile.

PMID- 8883337
TI  - Estimation of the weight and body condition of ostriches (Struthio camelus) from
      body measurements.
AB  - The body dimensions and weights of over 100 ostriches were analysed to
      investigate which body measurements provided the best estimators of bodyweight.
      The data were divided between growing and adult birds (below and above two years
      old) for regression analyses. The residual standard deviation of weight was 0.117
      for growing birds, using tibiotarsal length and abdominal girth as predictors.
      The analogous figure for adults was 0.078 using back length and abdominal girth.
      An assessment of body condition was made by calculating the average weight-for
      size of a bird from skeletal measurements which are unaffected by gross changes
      in weight, and then comparing it with its estimated or actual weight. These
      estimates of the weight of a typical ostrich should be useful in veterinary
      practice, particularly when the weight of a bird is required for the
      administration of medication.

PMID- 8883338
TI  - Effect of four therapeutic agents on Trichomonas phasiani carriage in pheasants.

PMID- 8883339
TI  - Plasma iron in elite horses at rest and after transport.

PMID- 8883340
TI  - Outbreak of Chrysomyia bezziana in Khoozestan province, Iran.

PMID- 8883341
TI  - Accelerated slaughter scheme.

PMID- 8883342
TI  - Disposal of rendered specified offal.

PMID- 8883343
TI  - Rabies and quarantine.

PMID- 8883344
TI  - BSE will fade 'close to extinction' by 2001.

PMID- 8883346
TI  - Observations on the epidemiology of gastrointestinal nematodes of farmed red deer
      in central southern England.
AB  - The epidemiology of the gastrointestinal nematodes of farmed red deer was
      followed over three years on two farms in north Hertfordshire. Worm counts on 10
      animals (four months to 10 years old) between November and March showed that
      mixed ostertagid infections were dominant with very small numbers of
      Trichostrongylus axei, Cooperia punctata and Oesophagostomum species also present
      in some individuals. An increase in the faecal nematode egg count of the hinds in
      summer was followed by an increase in pasture larval counts which peaked between
      September and November. Many calves had patent infections by the first week of
      September. Although the pasture larval counts were very low at the beginning of
      the 1989 season, anthelmintic treatment at turnout in May had little influence
      either on the summer increase in faecal egg count or on the subsequent pasture
      larval counts, and repeated treatments had only a moderate influence. However,
      the movement of one of the calving groups to an aftermath in mid-July did reduce
      the infection to which their calves were exposed. Nevertheless, none of the
      calves showed significant effects of parasitism when they were removed from the
      pasture and treated at weaning in early September.

PMID- 8883345
TI  - Protection of experimentally infected pigs by suilysin, the thiol-activated
      haemolysin of Streptococcus suis.
AB  - Three groups of three pigs were vaccinated either with vaccine VAC-SLY,
      containing purified suilysin derived from Streptococcus suis strain P1/7
      (serotype 2), or with vaccine VAC-SCF, containing most of the other extracellular
      antigens produced by strain P1/7 (but essentially free from suilysin), or with a
      placebo vaccine. The pigs were vaccinated twice at four weeks and six weeks of
      age and were challenged intravenously with S suis strain P1/7 at eight weeks of
      age. On the day of challenge, only the VAC-SLY vaccinated pigs showed an increase
      in haemolysin neutralisation titre. After challenge the placebo vaccinated pigs
      developed severe clinical signs characterised by lameness involving several
      joints, a depressed appearance, high temperatures and/or neurological signs. The
      VAC-SCF vaccinated pigs showed the same clinical signs but less severely. The VAC
      SLY vaccinated pigs were the least affected and showed only mild signs which
      subsided more quickly than those of the other groups. A post mortem investigation
      and histology of brain tissue samples confirmed the clinical findings; fibrinous
      arthritis was less severe and less frequently observed in the VAC-SLY vaccinated
      pigs than in the VAC-SCF or placebo vaccinated pigs, and none of the VAC-SLY
      vaccinated pigs had meningitis whereas two of the VAC-SCF and two of the placebo
      vaccinated pigs did so. All the samples of brain, lung and tarsus taken from the
      VAC-SLY vaccinated pigs were sterile whereas S suis was reisolated from most of
      these tissues from the other groups.

PMID- 8883347
TI  - Sigmoid caecal volvulus in a dairy cow treated by total typhlectomy.
AB  - A four-year-old pedigree Holstein, second lactation cow had been lethargic, with
      a reduced appetite, signs of colic and reduced milk yield for one day. There was
      a small swelling in the right paralumbar fossa and auscultation of this region
      revealed a tympanitic resonance (ping). An exploratory laparotomy revealed a
      sigmoid shaped caecal volvulus and extensive caecal necrosis. The condition was
      corrected surgically by a total typhlectomy. Recovery was slow for the first week
      after surgery but uneventful thereafter. One month later the cow was healthy,
      with normal faecal consistency, and in the milking herd. Over the following
      lactation the cow gave an excellent milk yield.

PMID- 8883348
TI  - Ovine psoroptic otoacariasis: an abattoir survey.

PMID- 8883349
TI  - Adrenal cortical carcinoma in a free-ranging mouflon (Ovis musimon).

PMID- 8883350
TI  - Fatal herpesvirus infection in a hedgehog (Erinaceus europaeus).

PMID- 8883351
TI  - Serological survey for avian viruses in houbara bustards (Chlamydotis undulata
      macqueenii).

PMID- 8883352
TI  - Standing thoracotomy and diaphragmatic herniorrhaphy in a cow.

PMID- 8883353
TI  - Genetic screening of dogs.

PMID- 8883354
TI  - FIV monitoring project.

PMID- 8883355
TI  - Erythromycin resistance of Campylobacter isolates from pigs.

PMID- 8883356
TI  - Bovine TB in south Sudan.

PMID- 8883357
TI  - Sequence and phylogenetic analysis of the VP7 gene of a bovine rotavirus with G6
      subtype.

PMID- 8883358
TI  - Inhibition of HTLV-I induction and virus-induced syncytia formation by
      oligodeoxynucleotides.
AB  - HTLV-I is an exogenous human retrovirus that is a causative agent of adult T cell
      leukemia (ATL). In addition to the structural genes (gag, pol and env), a gene
      termed pX is postulated to be associated with leukemogenesis in ATL. Since no
      effective chemotherapy is currently available, it is important to find suitable
      therapeutic means against ATL. Here, we tested the inhibitory effect of antisense
      oligodeoxynucleotides (ODNs) on HTLV-I infection in different systems. ODNs were
      synthesized with the phosphorothioate backbone targeted to either structural
      genes or transactivator genes. The phosphorothioate ODNs were found to have two
      distinct target sites to exert their effect on HTLV-I infection: 1) Several ODNs,
      including sense ODNs and random oligomers, blocked syncytium formation induced by
      HTLV-I at a concentration of 0.1 microM. Their inhibitory effect on syncytium
      formation seemed to be exerted in a nonantisense manner, most probably due to
      their interaction with the cell membrane. 2) Efficient suppression by ODNs of gag
      gene expression after chemical induction was observed in HTLV-I-transformed T
      cells in an antisense manner. In this suppression, tax-antisense ODN showed
      virtually complete inhibition of gag protein expression, but not RNA expression,
      at the concentration of 0.1 microM, whereas tax-sense ODN displayed a weak
      inhibitory effect. Our results suggest that the influence of the phosphorothioate
      compound should be considered from the aspect of two separated mechanisms of
      antiviral activity, the effects on early (viral adsorption) and late
      (translation) phase infection.

PMID- 8883359
TI  - Identification of the gene encoding the DNA (cytosine-5) methyltransferase of
      lymphocystis disease virus.
AB  - The gene encoding the DNA (cytosine-5) methyltransferase (m5C-MTase) of
      lymphocystis disease virus (flounder isolate, LCDV-1) has been identified by
      polymerase chain reaction (PCR) using oligonucleotide primers synthesized
      corresponding to different regions of the m5C-MTase gene of frog virus 3 (FV3). A
      DNA fragment of 487 bp was amplified using oligonucleotide primers L3 and R4
      which correspond to the nucleotide positions 87 to 109 and 530 to 550 of the m5C
      MTase gene of FV3, respectively. The DNA nucleotide sequence of the PCR product
      was determined by direct cycle sequencing. The alignment of the deduced amino
      acid sequence derived from the PCR product and the m5C-MTase protein of FV3
      revealed a homology of 55.4% identity and 29.1% similarity. The amino acid
      sequence which was found to be significantly homologous to the amino acid
      sequence deduced from the nucleotide sequence of the PCR product was located at
      the amino acid position 37 to 175 of the m5C-MTase of FV3 indicating the
      specificity of the amplified PCR product. The DNA nucleotide sequence of the LCDV
      1 genome corresponding to the 5' and 3' termini of the m5C-MTase gene was
      determined by primer walking. The locus of the m5C-MTase gene of LCDV-1 was
      identified within the EcoRI DNA fragment G of LCDV-1 (7.9 kbp; 0.947 to 0.034 map
      units). The m5C-MTase gene of LCDV-1 comprises 684 nucleotides coding for a
      putative protein of 228 amino acid residues. A high degree of amino acid sequence
      homology (53.3% identity and 25.8% similarity) was detected between the m5C-MTase
      of LCDV-1 and FV3.

PMID- 8883360
TI  - Sequence of rice hoja blanca tenuivirus RNA-2.
AB  - The sequence of rice hoja blanca tenuivirus RNA-2 is analysed and compared to its
      counter-part in rice stripe tenuivirus. The RNA encodes two proteins, in an
      ambisense arrangement. The 94 kD pc2, located in the complementary sense RNA, has
      several features typical of viral membrane (glyco)proteins, and also has regions
      of local homology to the glycoproteins of the Phleboviruses (Bunyaviridae). The
      23 kD pv2 lies in the viral sense RNA and has two small conserved domains that
      are almost exclusively found in retro-viral membrane glycoproteins. Its genome
      location is analogous to the NSm protein of several of the Bunyaviridae species,
      which is thought to have a membrane-related function. The two open reading frames
      are separated by a large intergenic region which, in common with the other
      tenuivirus ambisense RNA segments, has a short region that is highly conserved
      between RStV and RHBV. The significance of these results with respect to the
      virus structure and gene expression is discussed.

PMID- 8883361
TI  - Maize stripe tenuivirus RNA2 transcripts in plant and insect hosts and analysis
      of pvc2, a protein similar to the Phlebovirus virion membrane glycoproteins.
AB  - The complete sequence of the maize stripe tenuivirus (MStV) RNA2 was determined
      (3337 nucleotides). RNA2 contains two large open reading frames (ORFs) arranged
      in an ambisense orientation and specific RNAs of ca. 700 and 2600 nucleotides
      corresponding to the ORFs were detected in MStV-infected plants and planthoppers.
      The deduced amino acid sequence of the 23,500 MW protein (pv2) encoded by viral
      RNA2 (vRNA2) was similar to proteins encoded by the rice stripe (RStV) and rice
      hoja blanca tenuiviruses vRNA2. Sequence analysis suggested that pv2 is membrane
      associated. The 93,900 MW protein (pvc2) encoded by viral complementary MStV RNA2
      (vcRNA2) was similar to the 94,000 MW protein of RStV RNA2 and to the virion
      membrane glycoproteins for Phlebovirus members of the Bunyaviridae. The
      phlebovirus glycoprotein cleavage site was similar to a region in the MStV and
      RStV proteins suggesting that the tenuivirus pvc2 may be processed analogous to
      the phlebovirus glycoproteins.

PMID- 8883362
TI  - Sequence analysis of the complete S genomic segment of a newly identified
      hantavirus isolated from the white-footed mouse (Peromyscus leucopus):
      phylogenetic relationship with other sigmodontine rodent-borne hantaviruses.
AB  - Four Corners (FC) or Sin Nombre virus, a hantavirus harbored by the deer mouse
      (Peromyscus maniculatus), is the principal etiologic agent of hantavirus
      pulmonary syndrome (HPS). Recently, a hantavirus, designated New York (NY) virus,
      isolated from a white-footed mouse (Peromyscus leucopus) captured on Shelter
      Island, New York, was molecularly linked to a fatal case of HPS occurring in the
      northeastern United States. To clarify the genetic and phylogenetic relationship
      between NY and FC viruses and other sigmodontine rodent-borne hantaviruses, we
      amplified and sequenced the entire S genomic segment of NY virus. The S segment
      of NY virus was 2078 nucleotides long, with an open reading frame of 1284
      nucleotides in the virus complementary strand, capable of encoding a protein of
      428 amino acids, and with a 752-nucleotide long 3'-noncoding region, comprised of
      numerous imperfect repeats. Pairwise analysis indicated that NY virus was more
      similar to FC virus than to other sigmodontine rodent-borne hantaviruses,
      differing from strains of FC virus by 16.6-17.8% and 7.0-8.2% at the nucleotide
      and amino acid levels, respectively. As determined by the maximum parsimony and
      neighbor-joining methods, NY virus formed a separate lineage from FC virus and
      was phylogenetically distinct from hantaviruses harbored by other sigmodontine
      rodents. Whether or not NY and FC viruses represent distinct viral species is
      unclear. Further analyses of hantaviruses harbored by white-footed mice are
      needed to clarify the genetic diversity and evolution of Peromyscus-borne
      hantaviruses.

PMID- 8883363
TI  - Unique and conserved features of Tula hantavirus M gene encoding envelope
      glycoproteins G1 and G2.
AB  - The sequence of the genomic M segment encoding the surface glycoproteins G1 and
      G2 of wild-type Tula hantavirus (TUL) has been determined. Analyses of M
      nucleotide sequences show that TUL is genetically distinct from other
      hantaviruses. Comparison to ten currently known hantavirus G1G2 amino acid
      sequences points out several, presumably functional, regions with substantial
      homology indicating a common ancestry and similar evolutionary pathways for all
      members of the Hantavirus genus.

PMID- 8883364
TI  - Hamster polyomavirus-encoded proteins: gene cloning, heterologous expression and
      immunoreactivity.
AB  - The hamster polyomavirus (HaPV) is associated with spontaneously appearing skin
      epithelioma of the Syrian hamster Z3 strain. Virus particles prepared from the
      skin epithelioma cause lymphoma and leukemia when injected into newborn hamsters
      from a distinct Syrian hamster colony (HaP); in contrast to the skin epithelioma
      the hemopoietic tumors are virus free but accumulate viral DNA. To study the
      humoral immune response of HaPV-infected Z3 hamsters we produced recombinant HaPV
      proteins in Escherichia coli as beta-galactosidase-, TrpE- and dihydrofolate
      reductase-fusion proteins or as non-fused proteins. Recombinant plasmids carried
      segments of all putative early and late HaPV proteins. The recombinant proteins
      were detected in stained SDS polyacrylamide gels and in Western blots using
      monoclonal anti-TrpE and anti-beta-galactosidase antibodies and sera of HaPV
      infected hamsters. Sera from HaPV-infected Z3 hamsters and crude lysates of all
      clones were applied to Western blots to characterize the humoral immune response
      in the animals. HaPV-specific antibodies were found to be directed against early
      protein segments translated from the first common exon and from the second unique
      exon of LT and MT, resp., as well as against the late proteins VP1 and VP2/3. The
      almost complete VP2 was recognized by all sera whereas VP1 was detected only by a
      half of the sera. Our data suggest the presence of at least 2 immunodominant
      regions in VP2, one in the C-terminal VP1 and at least 4 in early proteins.

PMID- 8883365
TI  - Specific binding of polypyrimidine tract binding protein and hnRNP A1 to HIV-1
      CRS elements.
AB  - The human immunodeficiency virus (HIV) Rev and human T-cell leukemia virus (HTLV)
      Rex proteins regulate viral RNA processing. Both proteins act to overcome the
      block to viral structural gene expression, at least in part, by reversing the
      inhibitory effect of intronic RNA sequences, termed cis-acting repressive (CRS)
      sequences. Using HTLV type II (HTLV-II) as a model, we recently showed that the
      function of a 5' long terminal repeat (LTR) CRS correlates with in vitro binding
      by both polypyrimidine tract binding (PTB) protein (also known as hnRNP I) and
      hnRNP A1 to CRS RNA (1,2). Using radioimmunoprecipitation of proteins ultraviolet
      (UV) crosslinked to each HIV CRS RNA with monoclonal anti-hnRNP antibodies, we
      now demonstrate that hnRNP I and hnRNP A1 bind to two different HIV-1 CRS RNAs.
      In addition, we show that hnRNP I and hnRNP A1 binding to HIV-1 CRS RNAs can be
      specifically competed by HTLV-II CRS RNAs using electrophoretic mobility shift
      assay (EMSA)/UV crosslinking assays. Binding by both hnRNP I and hnRNP A1 to HIV
      1 and HTLV-II CRS RNAs suggests a role for these proteins in CRS function that
      may be influenced by the Rev and Rex proteins, respectively.

PMID- 8883366
TI  - Completion of the Norwalk virus genome sequence.
AB  - Norwalk virus (NV) is the prototype human calicivirus, and causes epidemic
      outbreaks of acute gastroenteritis. The sequence and predicted genome
      organization of NV and a NV-like virus [Southampton virus (SHV)] suggested they
      are similar viruses at the nucleotide and amino acid level, although SHV was
      reported to be antigenically distinct from NV. A recent review described the
      discovery of an additional 12 nucleotides at the 5' end of SHV and prompted us to
      investigate the possibility of additional nucleotides at the 5' end of the NV
      genome. The results obtained by homopolymeric tailing of NV cDNA with dCTP and
      dATP showed 12 additional nucleotides also are present on the NV genomic RNA.
      These data are important with respect to the biology of the virus, and make the
      genome sequence of NV complete.

PMID- 8883367
TI  - Sequence determination of the extreme 5' end of equine arteritis virus leader
      region.
AB  - The extreme 5' end of the leader sequence of four equine arteritis virus (EAV)
      strains was obtained by using rapid amplification of cDNA end method (5' RACE),
      and sequenced. Seventeen more nucleotides were added upstream of the 5' end of
      the EAV published genomic sequence. A common feature among the analyzed EAV
      isolates was the presence of an AUG start codon within the added sequence and the
      appearance of an intraleader open reading frame (ORF) of 111 nucleotides which
      was predicted to encode a peptide of 37 amino acids. The role of this putative
      intraleader ORF has yet to be determined.

PMID- 8883368
TI  - Voices of impoverished Brazilian women: health implications of roles and
      resources.
AB  - This qualitative study was based on individual interviews with 75 Brazilian women
      in an impoverished peri-urban squatter community (favela) in southeastern Brazil.
      The purposes of the study were to describe women's role involvement in domestic
      and employment contexts; identify stresses and satisfactions of maternal,
      spousal, and employment roles; and assess personal and environmental role
      constraints and resources from the perspective of women's health. The analytic
      approach to the interview data was qualitative content analysis, through which
      thematic categories of maternal, spousal, and employment role satisfactions and
      stresses were identified by the researchers. Women's unrelenting work in the face
      of harsh social and economic environments was a broad theme woven throughout the
      women's descriptions of their lives. The confluence of role constraints affecting
      the participants' lives included poverty, marginalization, abuse, and lack of
      support and recognition by partners and society. In order to overcome great
      adversity and meet heavy role demands, these women relied on self, faith in God,
      family, and health resources. Implications for women's health promotion are
      discussed.

PMID- 8883369
TI  - Gender and ethnic differences in the prevalence of alcohol, cigarette, and
      illicit drug use over time in a cohort of young Hispanic adolescents in south
      Florida.
AB  - The purpose of this study was to describe patterns of substance use among young
      Hispanic adolescents of Cuban and Central/South American heritage, many of whom
      are recent immigrants to the U.S. At present there are very little epidemiologic
      data on these Hispanic ethnic subgroups, particularly for girls. A cohort of 848
      middle school boys and girls in Miami, Florida completed questionnaires in 7th,
      8th, and 9th grades concerning their use of alcohol, cigarettes, marijuana, and
      other illicit drugs. African Americans and White non-Hispanics were used as
      comparison groups. In general, White non-Hispanics and U.S.-born Hispanics had
      the highest lifetime and past year prevalence rates of substance use. While no
      statistically significant gender differences were found for any of the
      racial/ethnic groups, the use of substances among Hispanic girls often exceeded
      that of their male counterparts. A progressive increase in use of alcohol,
      cigarettes, marijuana, and other illicit drugs was evident over the two and one
      half year duration of the study for both gender groups.

PMID- 8883370
TI  - Birth practice patterns in urban slums of Dhaka, Bangladesh.
AB  - This study describes the patterns of birth related practices amongst women from
      an urban slum population in Dhaka city during December 1988 to May 1989. A
      household census identified all resident women of childbearing age in Rajabazar
      ward of Dhaka city. Of the 1017 women so identified, 289 women who had given
      birth to their last child over the previous five years were randomly selected for
      interview using a structured interview schedule. To observe actual birth
      practices, sixteen women pregnant for six months or more at the time of the
      census were followed-up to the immediate post-natal period. Eight local
      traditional birth attendants (TBAs) were interviewed informally to obtain
      insights about birthing techniques. A case study for a typical 'normal' delivery
      is presented and discussed.

PMID- 8883371
TI  - Maternal psychological distress: the role of children's health.

PMID- 8883372
TI  - Synthesis of kojitriose using silicon-tethered glycosidation.
AB  - Reaction of 3,4,6-tri-O-acetyl-beta-D-glucopyranosyl chloride (1) with potassium
      phenylselenate gave phenyl 3,4,6-tri-O-acetyl-1-seleno-alpha, beta-D
      glucopyranoside (2) in 59% yield. Silylation of benzyl 3,4,6-tri-O-benzyl-beta-D
      glucopyranoside (4) with ethyl 3,4,6-tri-O-benzyl-2-O-chlorodimethylsilyl-1-thio
      beta -D-glucopyranoside gave benzyl 2-O-(3,4, 6-tri-O-benzyl-1-S-ethyl-1-thio
      beta-D-glucopyranos-2-O-yldimet hylsilyl)-3,4,6,-tri-O-benzyl-beta-D
      glucopyranoside (5) in 35% yield. Reaction of 5 with N-iodosuccinimide in
      nitromethane gave benzyl 2-O-(3,4, 6-tri-O-benzyl-alpha-D-glucopyranosyl)-3,4, 6
      tri-O-benzyl-beta-D-glucopyranoside (6) in 45% yield. Chlorodimethylsilylation of
      phenyl 3,4, 6-tri-O-acetyl-1-seleno-alpha-D-glucopyranoside (2 alpha) and
      reaction with 6 gave benzyl 2-O-[2-O-(3,4,6 -tri-O-acetyl-1-Se-phenyl-1-seleno
      alpha-D-glucopyranos-2-O-yld imethylsilyl) -3,4,6-tri-O-benzyl-alpha-D
      glucopyranosyl]-3,4,6-tri-O-benzyl-beta-D- glucopyranoside (7) in 82% yield.
      Intramolecular glycosidation of 7 using N-iodosuccinimide in nitromethane gave
      benzyl 2-O-[2-O-(3,4,6-tri-O-acetyl-alpha-D-glucopyranosyl)-3, 4,6-tri-O-benzyl
      alpha-D-glucopyranosyl]-3, 4,6-tri-O-benzyl-beta-D-glucopyranoside (8) in 45%
      yield. Deprotection of 8 gave kojitriose (9) in quantitative yield.
      Chlorodimethylsilylation of 1,3,4,6-tetra-O-benzyl-alpha, beta-D-fructofuranose
      (10) with dimethyldichlorosilane and pyridine followed by reaction with ethyl
      3,4, 6-tri-O-benzyl-1-thio-beta-D-glucopyranoside (3) gave ethyl 2-O-(1,3,4,6
      tetra-O-benzyl-alpha, beta-D-fructofuranosyloxydimethylsilyl)-3,4, 6-tri-O-benzyl
      1-thio-beta-D-glucopyranoside (11) in 85% yield. Chlorodimethylsilylation of
      1,3,4, 6-tetra-O-benzoyl-alpha-D-fructofuranose (12) with dimethyldicholorosilane
      and triethylamine followed by reaction with phenyl 3,4, 6-tri-O-acetyl-1-thio
      alpha-D-glucopyranoside (13) gave phenyl 2-O-(1,3,4, 6-tetra-O-benzoyl-alpha-D
      fructofuranosyloxydimethylsilyl)-3, 4,6-tri-O-acetyl-1-thio-alpha-D
      glucopyranoside (14) in 62% yield. Both 11 and 14 failed to undergo
      intramolecular glycosidation.

PMID- 8883373
TI  - Signal transduction in Rhizobium-induced nodule formation.

PMID- 8883374
TI  - The rab16B promoter of rice contains two distinct abscisic acid-responsive
      elements.
AB  - To localize abscisic acid (ABA)-inducible gene expression of rab16 genes, rab16A
      promoter was linked to the gusA reporter gene encoding beta-glucuronidase and
      introduced into rice (Oryza sativa L.) plants. The activity of rab16A promoter
      was induced by ABA and osmotic stresses in various tissues of vegetative and
      floral organs. In anthers and embryos, rab16A promoter was active in the absence
      of ABA. To elucidate cis-elements of the rab16 promoter that confer ABA-inducible
      expression, variously modified 40-bp fragments (-264 to -225) of the rab16B
      promoter were fused to a truncated (-46 bp) cauliflower mosaic virus 35S minimal
      promoter, and their activities in protoplasts were analyzed. The transient assays
      revealed that the 40-bp fragment consists of two separate ABA-responsive
      elements, motif 1 (AGTACGTGGC) and motif III (GCCGCGTGGC). Motif I and motif III
      are both required for ABA induction; however, each can substitute for the other.
      Further analyses of these motifs indicated that motif III has a distinct DNA
      sequence specificity as an ABA-responsive element from motif I, suggesting that
      the two motifs interact with different transcription factors in vivo.

PMID- 8883375
TI  - Tissue-specific expression and promoter analysis of the tobacco Itp1 gene.
AB  - The Nicotiana tabacum Itp1 gene (Ntltp1) encodes a small basic protein that
      belongs to a class of putative lipid transfer proteins. These proteins transfer
      lipids between membranes in vitro, but their in vivo function remains hotly
      debated. This gene also serves as an important early marker for epidermis
      differentiation. We report here the analysis of the spatial and developmental
      activity of the Ntltp1 promoter, and we define a sequence element required for
      epidermis-specific expression. Transgenic plants were created containing 1346 bp
      of the Ntltp1 promoter fused upstream of the beta-glucuronidase (GUS) gene. In
      the mature aerial tissues, GUS activity was detected predominantly in the
      epidermis, whereas in younger aerial tissues, such as the shoot apical meristem
      and floral meristem, GUS expression was not restricted to the tunica layer.
      Unexpectedly, GUS activity was also detected in young roots particularly in the
      root epidermis. Furthermore, the Ntltp1 promoter displayed a tissue and
      developmental specific pattern of activity during germination. These results
      suggest that the Ntltp1 gene is highly expressed in regions of the plant that are
      vulnerable to pathogen attack and are thus consistent with the proposed function
      of lipid transfer proteins in plant defense. Deletions of the promoter from its
      5' end revealed that the 148 bp preceding the translational start site are
      sufficient for epidermis-specific expression. Sequence comparison identified an
      eight-nucleotide palindromic sequence CTAGCTAG in the leader of Ntltp1, which is
      conserved in a number of other Itp genes. By gel retardation analysis, the
      presence of specific DNA-protein complexes in this region was demonstrated. The
      characterization of these factors may lead to the identification of factors that
      control early events in epidermis differentiation.

PMID- 8883376
TI  - Tissue-specific activity of two manganese superoxide dismutase promoters in
      transgenic tobacco.
AB  - In eukaryotes, manganese superoxide dismutase is a nuclear-encoded protein that
      scavenges superoxide radicals in the mitochondrial matrix. We have isolated two
      manganese superoxide dismutase genes from Nicotiana plumbaginifolia L. and fused
      the 5' upstream regulatory region of these genes to the beta-glucuronidase
      reporter gene. The two gene fusions displayed a differential tissue specificity
      in transgenic tobacco (Nicotiana tabacum). Promoter activity of the SodA1 gene
      fusion was found in the pollen, middle layer, and stomium of anthers, but was
      usually undetectable in vegetative organs of mature plants. The SodA2 gene fusion
      was expressed in the leaves, stems, roots, and flowers. SodA2 promoter activity
      was most prominent in the vascular bundles, stomata, axillary buds, pericycle,
      stomium, and pollen. Histochemical analysis of succinate dehydrogenase activity
      suggested that the spatial expression of the two gene fusions is generally
      correlated with mitochondrial respiratory activity.

PMID- 8883377
TI  - Fruit-specific expression of a defensin-type gene family in bell pepper.
      Upregulation during ripening and upon wounding.
AB  - We have isolated a 454-bp cDNA that encodes a novel fruit specific defensin from
      bell pepper (Capsicum annuum). The encoded 75-amino-acid polypeptide contains an
      N-terminal domain characteristic of a signal peptide and a 48-amino-acid mature
      domain named J1. The mature protein, from which the N-terminal amino acid
      sequence was determined, contains eight cysteines that from four intramolecular
      disulfide bridges, suggesting a monomeric form for J1. In healthy fruits J1 is
      undetectable at the green stage but high levels accumulate during ripening. In
      wound areas of the green fruit the accumulation of J1 dramatically increased,
      suggesting a role for J1 in the plant's defense response. Moreover, we have
      demonstrated that J1 possesses an antifungal activity. We have isolated and
      characterized the corresponding two homologous genes (j1-1 and j1-2) that exist
      in the bell pepper genome. Both genes are interrupted by the insertion, at the
      same position, of one intron of 853 bp for j1-1 and 4900 bp for j1-2. Northern
      blot and reverse transcriptase-polymerase chain reaction and restriction fragment
      length polymorphism analyses revealed that j1-1 transcripts are present only in
      fruits, only in trace amounts in mature green fruits, and that they accumulate to
      high levels in fully ripe fruits, whereas no j1-2 transcripts were detected in
      the samples monitored.

PMID- 8883378
TI  - Temporal and spatial distribution of ferredoxin isoproteins in tomato fruit.
AB  - Five ferredoxin (Fd) isoproteins (FdA, FdB, FdC, FdD, and FdE) were isolated from
      tomato (Lycopersicon esculentum cv Momotaro) fruit. These isoproteins showed
      differential temporal and spatial accumulation patterns. FdA and FdC were present
      in leaves. FdE was present in roots, and FdB and FdD were fruit-specific. During
      fruit growth, the relative abundance of FdA decreased and that of FdE increased.
      The FdE/FdA ratio was higher in the inner tissues of the fruit than in the outer
      tissue, and it was correlated with starch accumulation. In darkgrown fruit the
      contents of FdA, FdB, and FdC, as well as chlorophyll, decreased remarkably
      relative to their light-grown counterparts; however, the contents of FdE and
      starch did not change significantly. Under in vitro conditions FdE showed higher
      cytochrome c reduction activity than FdA and FdB. These results, together with
      their N-terminal sequences, indicate that both photosynthetic- and heterotrophic
      type Fd isoproteins are present in tomato fruit.

PMID- 8883379
TI  - Sulfur availability and the SAC1 gene control adenosine triphosphate sulfurylase
      gene expression in Chlamydomonas reinhardtii.
AB  - A Chlamydomonas reinhardtii adenosine triphosphate (ATP) sulfurylase cDNA clone
      (pATS1) was selected by complementing a mutation in the ATP sulfurylase gene
      (cysD) of Escherichia coli. E. coli cysD strains harboring pATS1 grow on medium
      containing sulfate as the sole sulfur source and exhibit ATP sulfurylase
      activity. The amino acid sequence of the C. reinhardtii ATP sulfurylase, derived
      from the nucleotide sequence of the complementing gene (ATS1), is 25 to 40%
      identical to that of ATP sulfurylases in other eukaryotic organisms and has a
      putative transit peptide at its amino terminus. ATP sulfurylase mRNA was present
      when cells were grown in sulfur-replete medium, but accumulated to higher levels
      when the cells were exposed to sulfur-limiting conditions. Furthermore, sulfur
      stress-induced accumulation of the ATS1 transcript was reduced in a strain
      defective in SAC1, a gene that is critical for acclimation to sulfur-limited
      growth.

PMID- 8883380
TI  - A low-CO2-inducible gene encoding an alanine: alpha-ketoglutarate
      aminotransferase in Chlamydomonas reinhardtii.
AB  - At low-CO2 (air) conditions, the unicellular green alga Chlamydomonas reinhardtii
      acquires the ability to raise its internal inorganic carbon concentration. To
      study this adaptation to low CO2, cDNA clones induced under low-CO2 growth
      conditions were selected through differential screening. One full-length clone is
      2552 bp, with an open reading frame encoding 521 amino acids. The deduced amino
      acid sequence shows about 50% identity with alanine: alpha-ketogutarate
      aminotransferase (Ala AT, EC 2.6.1.2) from plants and animals, and the mRNA of
      this clone increased 4- to 5-fold 4 h after cells were switched from high-CO2 to
      low-CO2 growth conditions. The expression of the enzyme and its activity also
      increased accordingly at low-CO2 growth conditions. To study the physiological
      role of Ala AT, a pyridoxal phosphate inhibitor, aminooxyacetic acid, was added
      at 40 microM to the growth medium when cells were beginning to adapt to low CO2.
      This caused a 30% decrease in the maximum photosynthetic rate in air-adapting
      cells 8 h later. The addition of the inhibitor also caused the cells to excrete
      glycolate, a photorespiratory intermediate, but did not change the apparent
      affinity of the cell for external CO2. These physiological studies are consistent
      with the assumption that Ala AT is involved in the adaptation to low-CO2
      conditions.

PMID- 8883381
TI  - Both 5' and 3' sequences of maize adh1 mRNA are required for enhanced translation
      under low-oxygen conditions.
AB  - Alcohol dehydrogenase-1 (ADH1) synthesis in O2-deprived roots of maize (Zea mays
      L.) results from induced transcription and selective translation of ADH1 mRNA.
      The effect of ADH1 mRNA sequences on message stability and translation was
      studied in protoplasts of the maize cell line P3377.5' capped and 3'
      polyadenylated mRNA constructs containing the firefly gene (luc) for luciferase
      (LUC) or the Escherichia coli gene (uidA) for beta-glucuronidase (GUS) coding
      region were synthesized in vitro and electroporated into protoplasts that were
      cultured at 40 or 5% O2. A LUC mRNA with a 17-nucleotide polylinker 5'
      untranslated region (UTR) was expressed 10-fold higher under aerobic conditions
      than under hypoxic conditions. Expression of five chimeric ADH1-GUS mRNAs was
      measured relative to this LUC mRNA. An mRNA containing the 5'-UTR and the first
      18 codons of adh1 in a translational fusion with the GUS coding region and
      followed by the 3'-UTR of adh1 was expressed 57-fold higher at 5% O2. Progressive
      deletion of adh1 5'-UTR and coding sequences reduced expression of the GUS-mRNA
      at 5% O2, but had little impact on expression of 40% O2. Enhancement of
      expression in hypoxic protoplasts conferred by the adh1 5'-UTR and the first 26
      codons decreased more than 3-fold when the adh1 3'-UTR was removed. In addition,
      the adh1 3'-UTR slightly inhibited expression in aerobic protoplasts. The
      physical half-lives of the GUS and LUC mRNAs were similar under both anaerobic
      and hypoxic conditions, indicating that expression levels were largely
      independent of mRNA stability. Thus, both adh1 5' and 3' mRNA sequences are
      required for enhanced translation in protoplasts under O2 deprivation.

PMID- 8883382
TI  - Regulated copper uptake in Chlamydomonas reinhardtii in response to copper
      availability.
AB  - A saturable and temperature-dependent copper uptake pathway has been identified
      in Chlamydomonas reinhardtii. The uptake system has a high affinity for copper
      ions (Km approximately 0.2 microM) and is more active in cells that are adapted
      to copper deficiency than to cells grown in a medium containing physiological
      (submicromolar to micromolar) copper ion concentrations. The maximum velocity of
      copper uptake by copper-deficient cells (169 pmol h-1 10(6) cells-1 or 62 ng min
      1 mg-1 chlorophyll) is up to 20-fold greater than that of fully copper
      supplemented cells, and the Km (approximately 2 x 10(2) nM) is unaffected. Thus,
      the same uptake system appears to operate in both copper-replete and copper
      deficient cells, but its expression or activity must be induced under copper
      deficient conditions. A cupric reductase activity is also increased in copper
      deficient compared with copper-sufficient cells. The physiological
      characteristics of the regulation of this cupric reductase are compatible with
      its involvement in the uptake pathway. Despite the operation of the uptake
      pathway under both copper-replete and copper-deficient conditions, C. reinhardtii
      cells maintained in fully copper-supplemented cells do not accumulate copper in
      excess of their metabolic need. These results provide evidence for a homeostatic
      mechanism for copper metabolism in C. reinhardtii.

PMID- 8883383
TI  - Novel molecular markers for late phases of the growth cycle of Arabidopsis
      thaliana cell-suspension cultures are expressed during organ senescence.
AB  - In an Arabidopsis thaliana T87-C3 cell-suspension culture, entry into the growth
      arrest phase is rapidly followed by a loss of cell viability. Three cDNA clones,
      SRG1, SRG2, and SRG3, corresponding to genes with transcripts that accumulate
      during these late phases, were isolated by the mRNA differential display method.
      Amino acid sequence analysis shows that the putative SRG1 protein is a new member
      of the Fe(II)/ascorbate oxidase superfamily, and that SRG2 codes for a protein
      with significant homology to beta-glucosidases. Significantly, all three SRG
      genes are expressed in senescing organs of Arbidopsis plants. Two previously
      characterized genes, SAG2 and SAG4, induced during natural senescence in
      Arabidopsis, were also found to be expressed in cell-suspension cultures and have
      expression kinetics similar to those observed for the SRG1 gene. Taken together
      these finding suggest that certain molecular events are common to both plant
      senescence and growth arrest in arabidopsis cell suspensions. Both
      internucleosomal cleavage of nDNA and an apparent compaction of chromatin, two
      characteristic features of programmed cell death in animal cells, have been
      observed in Arabidopsis cell cultures at a stage corresponding to loss of cell
      viability.

PMID- 8883384
TI  - The promoter for tomato 3-hydroxy-3-methylglutaryl coenzyme A reductase gene 2
      has unusual regulatory elements that direct high-level expression.
AB  - The promoter region of tomato (Lycopersicon esculentum) 3-hydroxy-3
      methylglutaryl coenzyme A reductase gene 2 (HMG2) has been analyzed using the
      transient expression of HMG2-luciferase fusions in red fruit pericarp. The mRNA
      for HMG2 accumulates to high level during fruit ripening, in a pattern that
      coincides with the synthesis of the carotenoid lycopene. Unlike most promoters,
      the region that is upstream of the HMG2 TATA element is not required for high
      level expression. The 180-bp region containing the TATA element, the 5'
      untranslated region, and the translation start site are comparable in strength of
      the full-length 35S cauliflower mosaic virus promoter. Pyrimidine-rich sequences
      present in the 5' untranslated leader are important in regulating expression.
      Also, the ATG start region has been found to increase translation efficiency by a
      factor of 4 to 10. An alternative hairpin secondary structure has been identified
      surrounding the HMG2 initiator ATG, which could participate in the translational
      regulation of this locus. HMG2 appears to be a novel class of strong plant
      promoters that incorporate unusual, positive regulators of gene expression.

PMID- 8883385
TI  - Isolation and characterization of mutants of Arabidopsis thaliana with increased
      resistance to growth inhibition by indoleacetic acid-amino acid conjugates.
AB  - Two mutants of Arabidopsis thaliana that are resistant to growth inhibition by
      indole-3-acetic acid (IAA)-phenylalanine have been isolated. Both mutants were 2-
      to 3-fold more resistant than wild type to inhibition by IAA-phenylalanine, IAA
      alanine, and IAA-glycine in root growth assays. The mutant icr1 (but not icr2)
      also shows some resistance to IAA-aspartate. Studies using 3H-labeled IAA
      phenylalanine showed that the uptake of conjugate from the medium by icr1 was the
      same as wild type and was reduced by about 25% in icr2. No differences in
      hydrolysis of the exogenous conjugate were detected between the mutants and their
      wild-type parents. There was no significant metabolism of the IAA released from
      the [3H]IAA-phenylalanine, whereas exogenous [3H]IAA was rapidly metabolized to
      two unidentified products considerably more polar than IAA. Analysis of a cross
      between icr1 and icr2 indicated that these mutations were at distinct loci and
      that their effects were additive, and preliminary mapping data indicated that
      icr1 and icr2 were located at the top and bottom of chromosome V, respectively.

PMID- 8883386
TI  - Synthesis of small heat-shock proteins is part of the developmental program of
      late seed maturation.
AB  - Small heat-shock proteins (sHSPs) accumulate in plants in response to high
      temperature stress. Specific sHSPs, the cytosolic class I and class II proteins,
      are also expressed in the absence of stress in maturing seeds of several species,
      and a role for these proteins in desiccation tolerance, dormancy, or germination
      has been hypothesized. We demonstrate that class I sHSPs are expressed during
      Arabidopsis seed development in a pattern similar to that previously observed in
      other species: they are first detected during mid-maturation, are most abundant
      in dry seeds, and decline rapidly during germination. Although the class I sHSP
      family in Arabidopsis appears to consist of four genes, expression of a single
      gene, Athsp 17.4, accounts for the majority of sHSPs in maturing seeds. sHSP
      levels were also examined in seeds of several Arabidopsis mutants with reduced
      sensitivity to abscisic acid inhibition, including aba1, abi1, and abi2, abi3-1,
      abi3-6, abi4, and abi5-1. The abi3-1 mutant has 10-fold reduced levels of sHSPs;
      sHSPs are undetectable in the abi3-6 mutant. All other mutants were
      indistinguishable from wild type. These results suggest that sHSP expression in
      seeds is regulated by the ABI3 response pathway and wild-type levels of sHSPs are
      not sufficient for seed dormancy and not necessary for desiccation tolerance.
      However, roles in either process cannot be ruled out. In total the data indicate
      that the expression of sHSPs in seeds is part of the normal developmental program
      of late seed maturation and the presence of sHSPs has adaptive significance for
      plant reproduction.

PMID- 8883387
TI  - Mechanism of proton permeation through chloroplast lipid membranes.
AB  - Electrical measurements were carried out to investigate the contribution of
      chloroplast lipids to the passive proton permeability of both the thylakoid and
      inner-envelope membranes. Permeability coefficient and conductance to protons
      were measured for solvent-free bilayers made from
      monogalactosyldiglyceride:digalactosyldiglycerid:
      sulfoquinovosyldiglyceride:phosphatidylglycerol (2:1:0.5:0.5, w/w) in the
      presence of a pH gradient of 7.4/8.1. The permeability coefficient for protons in
      glycolipids was 5.5 +/- 1.1 x 10(-4) cm s-1 (n = 14). To determine whether this
      high H+ permeability could be explained by the presence of lipid contaminants
      such as weak acids, we investigated the effects of (a) bovine serum albumin,
      which can remove some amphiphilic molecules such as free fatty acids, (b) 6
      ketocholestanol, which increases the membrane dipole potential, (c) oleic acid,
      and (d) chlorodecane, which increases the dielectric constant of the lipid
      bilayer. Our results show that free fatty acids are inefficient protonophores, as
      compared with carbonylcyanide-m-chlorphenythydrazone, and that the hypothesis of
      a weak acid mechanism is not valid with glycolipid bilayers. In the presence of
      deuterium oxide the H+ conductane was reduced significantly, indicating that
      proton transport through the glycolipid matrix could occur directly by a hydrogen
      bond process. The passive transport of H+ through the glycolipid matrix is
      discussed with regard to the activity of the thylakoid ATP synthase and the inner
      envelope H(+)-ATPase.

PMID- 8883388
TI  - Molecular and biochemical characterization of tomato farnesyl-protein
      transferase.
AB  - The prenylation of membrane-associated proteins involved in the regulation of
      eukaryotic cell growth and signal transduction is critically important for their
      subcellular localization and biological activity. In contrast to mammalian cells
      and yeast, however, the function of protein prenylation in plants is not well
      understood and only a few prenylated proteins have been identified. We partially
      purified and characterized farnesyl-protein transferase from tomato (Lycopersicon
      esculentum, LeFTase) to analyze its biochemical and molecular properties. Using
      Ras- and G gamma-specific peptide substrates and competition assays we showed
      that tomato protein extracts have both farnesyl-protein transferase and
      geranylgeranyl-protein transferase 1 activities. Compared with the heterologous
      synthetic peptide substrates, the plant-specific CaaX sequence of the ANJ1
      protein is a less efficient substrate for LeFTase in vitro. LeFTase activity
      profiles and LeFTase beta-subunit protein (LeFTB) levels differ significantly in
      various tissues and are regulated during fruit development. Partially purified
      LeFTase requires Zn2+ and Mg2+ for enzymatic activity and has an apparent
      molecular mass of 100 kD Immunoprecipitation experiments using anti-alpha LeFTB
      antibodies confirmed that LeFTB is a component of LeFTase but not of tomato
      geranylgeranyl-protein transferase 1. Based on their conserved bio-chemical
      activities, we expect that prenyltransferases are likely integrated with the
      sterol biosynthesis pathway in the control of plant cell growth.

PMID- 8883389
TI  - The major form of ADP-glucose pyrophosphorylase in maize endosperm is extra
      plastidial.
AB  - Preparations enriched in plastids were used to investigate the location of ADP
      glucose pyrophosphorylase (AGPase) in the developing endosperm of maize (Zea mays
      L.). These preparations contained more than 25% of the total activity of the
      plastid marker enzymes alkaline pyrophosphatase and soluble starch synthase, less
      than 2% of the cytosolic marker enzymes alcohol dehydrogenase and pyrophosphate,
      fructose 6-phosphate 1-phosphotransferase, and approximately 3% of the AGPase
      activity. Comparison with the marker enzyme distribution suggests that more than
      95% of the activity of AGPase in maize endosperm is extra-plastidial. Two
      proteins were recognized by antibodies to the small subunit of AGPase from maize
      endosperm Brittle-2 (Bt2). The larger of the two proteins was the major small
      subunit in homogenates of maize endosperm, and the smaller, less abundant of the
      two proteins was enriched in preparations containing plastids. These results
      suggest that there are distinct plastidial and cytosolic forms of AGPase, which
      are composed of different subunits. Consistent with this was the finding that the
      bt2 mutation specifically eliminated the extraplastidial AGPase activity and the
      larger of the two proteins recognized by the antibody to the Bt2 subunit.

PMID- 8883390
TI  - Phosphorylation of serine-15 of maize leaf sucrose synthase. Occurrence in vivo
      and possible regulatory significance.
AB  - Experiments were conducted to determine whether sucrose synthase (SuSy) was
      phosphorylated in the elongation zone of maize (Zea mays L.) leaves. The
      approximately 90-kD subunit of SuSy was 32P-labeled on seryl residue(s) when
      excised shoots were fed [32P]orthophosphate. Both isoforms of SuSy (the SS1 and
      SS2 proteins) were phosphorylated in vivo, and tryptic peptide-mapping analysis
      suggested a single, similar phosphorylation site in both proteins. A combination
      of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      and automated Edman sequencing analysis unequivocally identified the
      phosphorylation site in the maize SS2 protein as serine-15. This site was
      phosphorylated in vitro by endogenous protein kinase(s) in a strictly Ca(2+)
      dependent manner. A synthetic peptide, based on the phosphorylation site
      sequence, was used to identify and partially purify an endogenous Ca(2+)
      dependent protein kinase(s) from the maize leaf elongation zone and expanding
      spinach leaves. Phosphorylation of SuSy in vitro selectively activates the
      cleavage reaction by increasing the apparent affinity of the enzyme for sucrose
      and UDP, suggesting that phosphorylation may be of regulatory significance.
      Conservation of the phosphorylation site, and the sequences surrounding it, among
      plant species suggests that phosphorylation of SuSy may be widespread, if not
      universal, in plants.

PMID- 8883391
TI  - Genetic engineering of plant secondary metabolism. Accumulation of 4
      hydroxybenzoate glucosides as a result of the expression of the bacterial ubiC
      gene in tobacco.
AB  - The ubiC gene of Escherichia coli encodes chorismate pyruvatelyase, an enzyme
      that converts chorismate into 4-hydroxybenzoate (4HB) and is not normally present
      in plants. The ubiC gene was expressed in Nicotiana tabacum L. plants under
      control of a constitutive plant promoter. The gene product was targeted into the
      plastid by fusing it to the sequence for the chloroplast transit peptide of the
      small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. Transgenic
      plants showed high chorismate pyruvate-lyase activity and accumulated 4HB as beta
      glucosides, with the glucose attached to either the hydroxy or the carboxyl
      function of 4HB. The total content of 4HB glucosides was approximately 0.52% of
      dry weight, which exceeded the content of untransformed plants by at least a
      factor of 1000. Feeding experiments with [1,7-13C2]shikimic acid unequivocally
      proved that the 4HB that was formed in the transgenic plants was not derived from
      the conventional phenylpropanoid pathway but from the newly introduced chorismate
      pyruvate-lyase reaction.

PMID- 8883392
TI  - Severity of mutant phenotype in a series of chlorophyll-deficient wheat mutants
      depends on light intensity and the severity of the block in chlorophyll
      synthesis.
AB  - Analyses of a series of allelic chlorina mutants of wheat (Triticum aestivum L.),
      which have partial blocks in chlorophyll (Chl) synthesis and, therefore, a
      limited Chl supply, reinforce the principle that Chl is required for the stable
      accumulation of Chl-binding proteins and that only reaction centers accumulate
      when the supply of Chl is severely limited. Depending on the rate of Chl
      accumulation (determined by the severity of the mutation) and on the rate of
      turnover of Chl and its precursors (determined by the environment in which the
      plant is grown), the mutants each reach an equilibrium of Chl synthesis and
      degradation. Together these mutants generate a spectrum of phenotypes. Under the
      harshest conditions (high illumination), plants with moderate blocks in Chl
      synthesis have membranes with very little Chl and Chl-proteins and membrane
      stacks resembling the thylakoids of the lethal xantha mutants of barely grown at
      low to medium light intensities (which have more severe blocks). In contrast,
      when grown under low-light conditions the same plants with moderate blocks have
      thylakoids resembling those of the wild type. The wide range of phenotypes of Chl
      b-deficient mutants has historically produced more confusion than enlightenment,
      but incomparable growth conditions can now explain the discrepancies reported in
      the literature.

PMID- 8883393
TI  - Targeting of two Arabidopsis H(+)-ATPase isoforms to the plasma membrane.
AB  - More than 11 different P-type H(+)-ATPases have been identified in Arabidopsis by
      DNA cloning. The subcellular localization for individual members of this proton
      pump family has not been previously determined. We show by membrane fractionation
      and immunocytology that a subfamily of immunologically related P-type H(+)
      ATPases, including isoforms AHA2 and AHA3, are primarily localized to the plasma
      membrane. To verify that AHA2 and AHA3 are both targeted to the plasma membrane,
      we added epitope tags to their C-terminal ends and expressed them in transgenic
      plants. Both tagged isoforms localized to the plasma membrane, as indicated by
      aqueous two-phase partitioning and sucrose density gradients. In contrast, a
      truncated AHA2 (residues 1-193) did not, indicating that the first two
      transmembrane domains alone are not sufficient for plasma membrane localization.
      Two epitope tags were evaluated: c-myc, a short, 11-amino acid sequence, and beta
      glucuronidase (GUS), a 68-kD protein. The c-myc tag is recommended for its
      sensitivity and specific immunodetection. GUS worked well as an epitope tag when
      transgenes were expressed at relatively high levels (e.g. with AHA2-GUS944);
      however, evidence suggests that GUS activity may be inhibited when a GUS domain
      is tethered to an H(+)-ATPase complex. Nevertheless, the apparent ability to
      localize a GUS protein to the plasma membrane indicates that a P-type H(+)-ATPase
      can be used as a delivery vehicle to target large, soluble proteins to the plasma
      membrane.

PMID- 8883394
TI  - Purification and characterization of the reconstitutively active adenine
      nucleotide carrier from maize mitochondria.
AB  - The adenine nucleotide carrier from maize (Zea mays L. cv B 73) shoot
      mitochondria was solubilized with Triton X-100 and purified by sequential
      chromatography on hydroxyapatite and Matrex Gel Blue B in the presence of
      cardiolipin and asolectin. Sodium dodecyl sulfate-gel electrophoresis of the
      purified fraction showed a single polypeptide band with an apparent molecular
      mass of 32 kD. When reconstituted in liposomes, the adenine nucleotide carrier
      catalyzed a pyridoxal 5'-phosphate-sensitive ATP/ATP exchange. It was purified
      168-fold with a recovery of 60% and a protein yield of 0.25% with respect to the
      mitochondrial extract. Among the various substrates and inhibitors tested, the
      reconstituted protein transported only ADP, ATP, GDP, and GTP, and was inhibited
      by atractyloside, bongkrekate, phenylisothiocianate, pyridoxal 5'-phosphate, and
      mersalyl (but not N-ethylmaleimide). Maximum initial velocity of the
      reconstituted ATP/ATP exchange was determined to be 2.2 mumol min-1 mg-1 protein
      at 25 degrees C. The half-saturation constants and the corresponding inhibition
      constants were 17 microM for ATP, 26 microM for ADP, 59 microM for GTP, and 125
      microM for GDP. The activation energy of the ATP/ATP exchange was 48
      kilojoule/mol between 0 and 15 degrees C, and 22 kilojoule/mol between 15 and 35
      degrees C. Partial amino acid sequences showed that the purified protein was the
      product of the ANT-G1 gene sequenced previously (B. Bathgate, A. Baker, C.J.
      Leaver [1989] Eur J Biochem 183: 303-310).

PMID- 8883395
TI  - The electronic Plant Gene Register.

PMID- 8883396
TI  - Populations with sinusoidal birth trajectories.
AB  - Starting with a sinusoidal birth function, we derive an explicit expression for
      the associated wave of net maternity (R(t)). The phase shift and relative
      amplification of R(t) depend heavily on the cycle length of oscillation (T)
      relative to the mean age of net maternity (mu) and on the amplitude of
      oscillation of the birth function. For short cycle lengths (up to about 12
      years), the birth and R(t) functions are virtually identical. When the cycle
      length is long (over 120 years), R(t) is essentially equal to the ratio of the
      number of births at time t to that at time t-mu. The R(t) function oscillates
      with the same cycle length as the birth function, but it is not sinusoidal and
      its asymmetry increase as the amplitude of birth function increases. This paper
      breaks new ground by providing a complete description of the dynamics of the
      model, including an analysis of the sensitivity of R(t) to the amplitude of the
      birth function, which was not accessible to previous approaches.

PMID- 8883397
TI  - Therapeutic proteins and enzymes from genetically engineered yeasts.
AB  - Human proteins, including enzymes, manufactured with recombinant-DNA yeasts can
      be used to treat a variety of medical conditions; some redesign of molecular
      structure (and production techniques) should increase their specificity, efficacy
      and immunotolerance. Prevention and treatment of diseases due to reactive oxygen
      species (ROS) and reactive nitrogen species (RNS) may become possible.
      Therapeutic vaccines for some diseases may be produced by design-specification
      for particular desirable protein features, on an individual patient basis.

PMID- 8883398
TI  - p53 mutation is associated with high S-phase fraction in primary fallopian tube
      adenocarcinoma.
AB  - Fallopian tube carcinoma (FTC) is a rare but lethal gynaecological malignancy.
      Four out of seven FTCs were identified with three point missense mutations, one
      single base deletion and one silent point mutation in the p53 gene. Genital-type
      HPV sequences were not detected. The S-phase fraction of tumours with mutant and
      wild-type p53 was 25.74% (median) and 12.55% (median) respectively.

PMID- 8883399
TI  - Colocalisation of matrix metalloproteinase-9-mRNA and protein in human colorectal
      cancer stromal cells.
AB  - The matrix metalloproteinases (MMPs) are perceived as essential for tumour
      invasion and metastases. The purpose of this study was to determine the
      expression and cellular localisation of the 92 kDa type IV collagenase (MMP-9)
      protein and mRNA in human colorectal cancer (CRC). In CRC and matched normal
      mucosa specimens from 26 CRC patients, Northern blot hybridisation and Western
      blot analyses provide convincing evidence that MMP-9 is expressed in greater
      quantities in CRC than in normal tissue. The MMP-9 tumour to normal mucosa fold
      increase (T/N) was 9.7 +/- 7.1 (mean +/- s.d.) (P < 0.001) for RNA and 7.1 +/-
      3.9 (P < 0.001) for protein. The sites of MMP-9 mRNA and protein synthesis were
      colocalised in tumour stroma by in situ hybridisation and immunohistochemistry in
      26 CRC samples. Both MMP-9 mRNA and protein signals were strongest in the
      population of stromal cells concentrated at the tumour-stroma interface of an
      invading tumour. Furthermore, MMP-9-positive cells were identified as macrophages
      using an antimacrophage antibody (KP1) in serial sections from ten CRC samples.
      Given the persistent localisation of MMP-9-producing macrophages to the
      interphase between CRC and surrounding stroma, our observations suggest that MMP
      9 production is controlled, in part, by tumour-stroma cell interactions. Further
      studies are needed to determine the in vivo regulation of MMP-9 production from
      infiltrating peritumour macrophages.

PMID- 8883400
TI  - Up-regulation of urokinase-type plasminogen activator in squamous cell carcinoma
      of human larynx.
AB  - The expression of urokinase-type plasminogen activator (uPA) was investigated in
      squamous cell carcinoma of the human larynx. For this purpose, tissue extracts
      from 25 matched samples of normal mucosa and neoplastic larynx were compared for
      the levels of uPA activity as evaluated by a chromogenic PA assay and sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) zymography. Also,
      uPA antigen was quantified by enzyme-linked immunosorbent assay (ELISA) in 19
      cases. The results demonstrate a significant increase in the levels of uPA
      activity and protein in tumour tissue extracts, more pronounced in tumours with
      lymph node metastases. Immunohistochemistry performed on 70 biopsies showed that
      uPA positivity is present both in neoplastic cells and in fibroblast-like cells
      and macrophages. However, depending on the histological grading and invasive
      capacity of the tumour, a pronounced intra- and intertumoral heterogeneity in uPA
      staining was observed. In situ hybridisation confirmed the presence of uPA mRNA
      in both tumour and stromal cells. The present study provides experimental
      evidence for a role of uPA in the invasive growth of human laryngeal carcinoma.

PMID- 8883401
TI  - Expression of the androgen receptor and an androgen-responsive protein,
      apolipoprotein D, in human breast cancer.
AB  - Little is known regarding the activity and function of the androgen receptor (AR)
      in human breast cancer. In the present study AR was evaluated in untreated
      primary breast cancers using antisera to the amino- and carboxy-termini of the
      receptor and quantitated using colour video image analysis. A strong correlation
      between tissue concentration and percentage AR-positive cells was observed for
      each antiserum. However, comparison of percentage positive cells using the amino-
      and carboxy-terminal AR antisera in individual breast cancer specimens revealed a
      subset of tumours with discordantly increased staining for the carboxy terminus.
      These findings suggest the presence of amino-terminal-truncated AR in a
      proportion of breast cancer cells or presence of AR mutations or associated
      protein alterations that affect binding of the amino-terminal AR antiserum.
      Immunohistochemical expression of the androgen-regulated glycoprotein,
      apolipoprotein D (apo-D), was also evaluated in the breast cancer specimens.
      Focal positivity of apo-D staining, which did not always co-localise with AR
      positive cells, was observed within breast tumours. Furthermore, no correlation
      was evident between percentage positive cells stained for AR and apo-D in breast
      cancer specimens. These findings indicate that, although apo-D expression is
      androgen regulated in human breast cancer cell lines in vitro, its expression in
      primary breast cancers may be regulated by other factors. The expression of AR in
      primary breast cancers also suggests that the receptor may be involved in tumour
      responsiveness or in abnormal responses to endocrine therapies.

PMID- 8883402
TI  - A comparative study of detection of p53 mutations in human breast cancer by flow
      cytometry, single-strand conformation polymorphism and genomic sequencing.
AB  - The accuracy of immunodetection by dual parameter flow cytometry (FCM),
      polymerase chain reaction-mediated single strand conformation polymorphism (PCR
      SSCP) and genomic sequencing to detect p53 mutations were compared. Analysis by
      the last two techniques was restricted to exons 5-8. Initially, 110 breast
      tumours were screened for p53 expression by FCM. Seventy (64%) of tumours were
      immunopositive. Fifteen highly immunopositive and 15 completely immunonegative
      tumours were selected for further analysis by PCR-SSCP and genomic sequencing.
      Eleven out of 15 immunopositive tumours were found to have mutation by PCR-SSCP.
      Genomic sequencing confirmed the presence of mutation in 10 of these 11
      immunopositive tumours. Therefore, four immunopositive tumours failed to show
      mutation by SSCP and five by genomic sequencing. Of the 15 immunonegative
      tumours, one showed mutation by both PCR-SSCP and genomic sequencing and one
      tumour has undergone deletion of the p53 gene. Overall, immunoreactivity
      correlated with both PCR-SSCP and genomic sequencing in 80% of cases (24/30), and
      there was 96.5% (28/29) concordance between PCR-SSCP and genomic sequencing. We
      conclude that there is good concordance between mutations detected by PCR-SSCP
      and genomic sequencing, but immunochemical detection of p53 overexpression is not
      an absolute indicator of p53 gene mutation.

PMID- 8883403
TI  - Development and validation of a spectrophotometric assay for measuring the
      activity of NADH: cytochrome b5 reductase in human tumour cells.
AB  - As part of an 'enzyme-directed' approach to bioreductive drug development, we
      have measured the activity of NADH: cytochrome b5 reductase (B5R) in human cancer
      cell lines in order to assess the role of this enzyme in activating bioreductive
      drugs, and thus in influencing the cytotoxicity of these compounds. At present,
      there is no validated assay reported in the literature for measuring the activity
      of B5R in tumour cells, and current measurements have assumed that the enzyme
      activity can be measured either as the NADH-dependent reduction of cytochrome c
      or as the non-dicoumarol-inhibitable activity in the DT-diaphorase assay. Using p
      hydroxymercuribenzoate (pHMB) as an inhibitor of B5R, we have quantified the
      contribution of B5R to the NADH-dependent reduction of cytochrome c and to the
      overall reduction of cytochrome c in the DT-diaphorase assay. In the former we
      found that residual uninhibited activity remained in the presence of pHMB, in
      some cases accounting for up to 60% of the total reduction of cytochrome c. Thus,
      simply measuring the NADH-dependent reduction of cytochrome c consistently
      overestimated B5R activity. We also found that the non-dicoumarol-inhibitable
      activity in the DT-diaphorase assay underestimated B5R activity, especially in
      cell lines with high DT-diaphorase activity. Therefore, we have developed a
      spectrophotometric assay for measuring B5R activity as the pHMB-inhibitable NADH
      dependent reduction of cytochrome c. This has been used to measure the B5R
      activity of a panel of 22 human tumour cell lines, in which we found 7-fold and 3
      fold variations in activity expressed per cell or per mg protein respectively.

PMID- 8883404
TI  - Treatment of ovarian cancer with photodynamic therapy and immunoconjugates in a
      murine ovarian cancer model.
AB  - In photodynamic therapy (PDT), photosensitisers accumulate somewhat
      preferentially in malignant tissues; photoactivation with appropriate wavelength
      of light release toxic molecular species which lead to tumour tissue death. In
      order to target ovarian cancer with increased specificity, a chlorin-based
      photosensitiser (chlorin e6 monoethylendiamine monoamide) was conjugated to
      OC125, a monoclonal antibody recognising an antigen expressed in 80% of non
      mucinous ovarian cancers. In previous work, this immunoconjugate (IC) was shown
      to be selectively phototoxic to cancer cells from ovarian cancer patients ex vivo
      and to localise preferentially in ovarian cancer tissue in vivo. In this study we
      report results from in vivo phototoxicology and photodynamic treatment studies
      using this IC in a murine model for ovarian cancer. A comparison of single vs
      multiple treatments was also made. For in vivo experimentation, Balb C nude mice
      were injected with 30 x 10(6) NIH:OVCAR 3 cancer cells to create an ascitic
      tumour model. Animals were then given intraperitoneal injections of the
      immunoconjugate (0.5 mg kg-1). Twenty-four hours later the intraperitoneal
      surfaces were exposed to 656 nm light from an argon-ion pumped-dye laser (50 mW,
      656 nm), using a cylindrical diffusing tip fibre. The overall treatment was given
      either once or multiply. No animals died from treatment complications. Twenty
      four hours following one and three PDT treatments, the percentage of viable
      tumour cells in the ascites of the treated animals analysed ex vivo was 34% and
      5% of control for one and three treatments respectively. With respect to
      survival, all control mice (n = 18) died between 30 and 50 days. However, for
      those treated three times (n = 10), 40% were still alive after 50 days, and for
      those treated four times (n = 12) 58% were alive after 50 days. Evaluation with
      log-rank test revealed a significant survival with intraperitoneal PDT compared
      with controls (P = 0.0006). These preliminary results suggest that PDT with an
      OC125 immunoconjugate may be an effective therapy for the management of advanced
      ovarian cancer. Clinical application of this therapy needs to be further
      optimised and may require multiple treatments, similar to fractionated radiation
      therapy and cyclic chemotherapy, in order to control malignant disease with
      acceptable toxicity to normal tissue.

PMID- 8883405
TI  - Differential effects of staurosporine analogues on cell cycle, growth and
      viability in A549 cells.
AB  - Staurosporine is a potent but non-specific kinase inhibitor. It has served as
      synthetic template for a variety of analogues, the indolocarbazoles, UCN-01 and
      CGP 41251, and the bisindolylmaleimides, Ro 31-8220 and GF 109203X, were
      investigated as growth inhibitors of human-derived A549 human lung adenocarcinoma
      cells. They were compared with respect to (1) effect on the cell cycle, (2) time
      dependency of growth arrest and (3) cytotoxic potency. Cells were exposed for 1,
      2 and 4 days, or for 6, 12 and 24 h in the case of cycle-synchronised cells, to
      staurosporine analogues at concentrations at which they inhibited growth by 80%
      after 4 day exposure. Staurosporine and UCN-01 retarded cells in G0/1, and CGP
      41251 appeared to inhibit cell growth without cell cycle specificity. Ro 31-8220
      slowed progression of synchronised cells through the cycle; over a longer time
      period it induced a weak block in G2/M. GF 109203X induced potent G2/M arrest in
      synchronised cells. This was not so apparent in asynchronous cells, which by day
      4 were slowed in G0/1 instead. Growth arrest induced by these inhibitors was more
      potent after incubation for 4 rather than 2 days. Incubation for 1 day followed
      by maintenance in drug-free medium for 3 days was sufficient to exert some
      cytostasis. The differences between cytotoxic and cytostatic concentrations, the
      former measured by release from cells of lactate dehydrogenase, were 15 000-fold
      for staurosporine, 300-fold for UCN-01, approximately 400-fold for CGP 41251, 25
      fold for Ro 31-8220 and approximately 4-fold for GF 109203X. The results show
      that PKC-selective staurosporine analogues differ with respect to the mechanisms
      by which they interfere with the cell cycle. The necessity of long-term exposure
      for effective growth inhibition and the considerable margin between cytostatic
      and acute cytotoxic indolocarbazole concentrations are findings which might
      influence the planning and interpretation of clinical trials of these kinase
      inhibitors.

PMID- 8883406
TI  - Fluorescence ratio imaging of interstitial pH in solid tumours: effect of glucose
      on spatial and temporal gradients.
AB  - Tumour pH plays a significant role in cancer treatment. However, because of the
      limitations of the current measurement techniques, spatially and temporally
      resolved pH data, obtained non-invasively in solid tumours, are not available.
      Fluorescence ratio imaging microscopy (FRIM) has been used previously for
      noninvasive, dynamic evaluation of pH in neoplastic tissue in vivo (Martin GR,
      Jain RK 1994, Cancer Res., 54, 5670-5674). However, owing to problems associated
      with quantitative fluorescence in thick biological tissues, these studies were
      limited to thin (50 microns) tumours. We, therefore, adapted the FRIM technique
      for pH determination in thick (approximately 2 mm) solid tumours in vivo using a
      pinhole illumination-optical sectioning (PIOS) method. Results show that (1)
      steep interstitial pH gradients (5 microns resolution), with different spatial
      patterns, exist between tumour blood vessels; (2) pH decreased by an average of
      0.10 pH units over a distance of 40 microns away from the blood vessel wall, and
      by 0.33 pH units over a 70 microns distance; (3) the maximum pH drop, defined as
      the pH difference between the intervessel midpoint and the vessel wall, was
      positively correlated with the intervessel distance; (4) 45 min following a
      systemic glucose injection (6 g kg-1 i.v), interstitial pH gradients were shifted
      to lower pH values by an average of 0.15 pH units, while the spatial gradient
      (slope) was maintained, when compared with preglucose values. This pH decrease
      was not accompanied by significant changes in local blood flow. pH gradients
      returned to near-baseline values 90 min after glucose injection; (5) interstitial
      tumour pH before hyperglycaemia and the glucose-induced pH drop strongly depended
      on the local vessel density; and (6) sodium bicarbonate treatment, either acute
      (1 M, 0.119 ml h-1 for 3 h i.v.) or chronic (1% in drinking water for 8 days),
      did not significantly change interstitial tumour pH. Modified FRIM may be
      combined with other optical methods (e.g. phosphorescence quenching) to evaluate
      non-invasively the spatial and temporal characteristics of extracellular pH,
      intracellular pH and pO2 in solid tumours. This will offer unique information
      about tumour metabolism and its modification by treatment modalities used in
      different cancer therapies.

PMID- 8883407
TI  - Dissection of tumour and host cells from target organs of metastasis for testing
      gene expression directly ex vivo.
AB  - We report on a new methodology which allows the direct analysis ex vivo of tumour
      cells and host cells (lymphocytes, macrophages, endothelial cells) from a
      metastasised organ (liver or spleen) at any time point during the metastatic
      process and without any further in vitro culture. First, we used a tumour cell
      line transduced with the bacterial gene lacZ, which permits the detection of the
      procaryotic enzyme beta-galactosidase in eukaryotic cells at the single cell
      level thus allowing flow adhesion cell sorting (FACS) analysis of tumour cells
      from metastasised target organs. Second, we established a method for the
      separation and enrichment of tumour and host cells from target organs of
      metastasis with a high viability and reproducibility. As exemplified with the
      murine lymphoma ESb, this new methodology permits the study of molecules of
      importance for metastasis or anti-tumour immunity (adhesion, costimulatory and
      cytotoxic molecules, cytokines, etc.) at the RNA or protein level in tumour and
      host cells during the whole process of metastasis. This novel approach may open
      new possibilities of developing strategies for intervention in tumour
      progression, since it allows the determination of the optimal window in time for
      successful treatments. The possibility of direct analysis of tumour and host cell
      properties also provides a new method for the evaluation of the effects of
      immunisation with tumour vaccines or of gene therapy.

PMID- 8883408
TI  - Prediction of radiotherapy response of cervical carcinoma through measurement of
      proliferation rate.
AB  - Estimation of tumour proliferation may allow the design of individualised
      radiotherapy schedules to optimise response. This prospective study correlates
      the tumour proliferation rate of cervical carcinoma with response to conventional
      radiotherapy. The potential tumour cell doubling rate (Tpot) was estimated
      following flash labelling of the tumours in vivo using the DNA precursor,
      bromodeoxyuridine (BrdUrd); samples were analysed by flow cytometry. Tumour
      ploidy, DNA index and mitotic count were also assessed as was histological grade
      and type. Multiple biopsies from each tumour were obtained from 121 women. The
      median Tpot was 4.0 days, median S-phase duration 12.8 h and median adjusted
      labelling index 9.8%. Higher BrdUrd labelling was seen in patients who developed
      pelvic tumour recurrence following radiotherapy. This was the only
      biological/histological parameter with univariate and multivariate significance
      in relation to locoregional recurrence (P = 0.006 and P = 0.034 respectively).
      This study represents the first assessment of Tpot in relation to long-term
      response of cervical tumours treated by radiotherapy treatment. The association
      of high BrdUrd labelling and poor pelvic disease-free survival indicates the need
      for further research into the potential of radiotherapy schedule alteration to
      reflect tumour proliferation. The predictive value may be enhanced by combination
      with other biological parameters.

PMID- 8883409
TI  - Irreversible loss of the oestrogen receptor in T47D breast cancer cells following
      prolonged oestrogen deprivation.
AB  - The development of antioestrogen resistance is a major clinical obstacle
      encountered in the treatment of breast cancer. By long-term growth in oestrogen
      free medium, we have derived an oestrogen-independent, anti-oestrogen resistant
      cell line from the oestrogen receptor (ER)-positive, oestrogen-dependent T47D
      human breast cancer cell line. This cell line grows maximally in oestrogen-free
      medium and is resistant to all tested antioestrogens. This cell line does not
      express any measurable amounts of ER mRNA or protein and, in short-term studies,
      these cells show no response to either oestrogens or antioestrogens. However,
      return of these cells to oestrogen-containing medium for more than 8 weeks
      resulted in the re-expression of ER mRNA and protein. Subsequent limiting
      dilution subcloning of the T47D:C4 line revealed two phenotypically distinct
      clones, one which did not express measurable ER after long-term growth in
      oestrogen-containing medium and one which expressed ER mRNA and protein after a
      number of weeks in oestrogen-containing medium. In the absence of oestrogen, both
      types of cells are ER-negative as determined by Northern and Western blotting and
      lack of any oestrogen-dependent responses. The clone which re-expresses the ER
      (T47D:C4:5W) now responds to E2 with a 50% increase in growth and a 30-fold
      induction of an ER-responsive luciferase reporter construct. Long-term growth of
      the stably ER-negative clone (T47D:C4:2W) causes no measurable oestrogen-mediated
      responses, as assessed by ER expression, growth stimulation or luciferase
      induction. Interestingly, ER mRNA can be detected in both cell types by using
      reverse transcriptase-polymerase chain reaction (RT-PCR). This suggests that the
      ER mRNA present in the T47D:C4:2W clone is either inefficiently translated or is
      present at such a low level as to be functionally irrelevant. These novel clonal
      cell lines will prove to be invaluable in the study of the regulation of ER
      expression and regulatory pathways leading to oestrogen-independent growth.

PMID- 8883410
TI  - E-cadherin relates to EGFR expression and lymph node metastasis in primary breast
      carcinoma.
AB  - Expression of the calcium-dependent cell-cell adhesion molecule E-cadherin has
      been examined in 187 primary breast carcinomas using an immunohistochemical
      technique. The pattern and extent of reactivity has been correlated with
      clinicopathological data including tumour type, grade and lymph node status and
      with other prognostic parameters including oestrogen receptor (ER) status,
      expression of c-erbB-2, pS2 protein and epidermal growth factor receptor (EGFR).
      Two patterns of E-cadherin staining were observed in carcinomas, membrane
      reactivity and a diffuse cytoplasmic staining. A marked difference in expression
      of E-cadherin was observed between infiltrating lobular carcinomas (ILC) and
      infiltrating ductal carcinomas (IDC), the former showing complete loss of
      membrane staining, whereas 93% of IDC retained some level of expression. In IDC
      reactivity was not related to tumour grade but there was a significant
      association between reduced membrane levels of E-cadherin and the presence of
      lymph node metastasis, and a highly significant correlation between the presence
      of cytoplasmic E-cadherin and metastasis. A significant relationship was also
      demonstrated between reduced E-cadherin reactivity and expression of EGFR. These
      findings emphasise the complexity of control of E-cadherin in breast carcinomas
      and provide evidence of a link between membrane signalling pathways and
      modulation of E-cadherin expression.

PMID- 8883411
TI  - Associations between insulin-like growth factors and their binding proteins and
      other prognostic indicators in breast cancer.
AB  - Recent studies have suggested that insulin-like growth factors (IGFs) and insulin
      like growth factor binding proteins (IGFBPs) may be implicated in the development
      and progression of breast cancer. Prostate-specific antigen (PSA), a serine
      protease, may play a role in the regulation of IGFs' function through cleavage of
      IGFBP-3, resulting in release of active IGFs from IGFBP-3. As IGFs, IGFBPs and
      PSA are all present in breast cancer, possible associations among these proteins
      were speculated. In this study, we have measured PSA, IGF-I, IGF-II, IGFBP-1 and
      IGFBP-3 in tumour tissue cytosols from 200 women with primary breast cancer, and
      have examined relationships between IGFs or IGFBPs and PSA along with other
      markers, including p53 protein, steroid hormone receptors (oestrogen and
      progesterone), cathepsin-D, epidermal growth factor receptor, Her-2/neu protein,
      S-phase fraction and DNA ploidy. Correlations or associations between PSA and IGF
      I, IGF-II, IGFBP-1 or IGFBP-3 were not observed. IGF-II was positively correlated
      with both IGFBP-3 and IGFBP-1. IGF-I was not associated with either of the two
      binding proteins, nor with IGF-II. Both IGF-II and IGFBP-3 were inversely
      associated with the oestrogen receptor, and IGFBP-3 was also positively
      associated with S-phase fraction. Our finding of IGF-II and IGFBP-3 in
      association with unfavourable prognostic indicators of breast cancer suggests
      that IGFs may be involved in the progression of breast cancer.

PMID- 8883412
TI  - Disruption of the circadian patterns of serum cortisol in breast and ovarian
      cancer patients: relationships with tumour marker antigens.
AB  - Few data are available on the circadian rhythmicity in cancer patients. Since
      monitoring the disease usually implies the follow-up of blood concentrations of a
      number of biological variables, it would be of value to examine the profile of
      the circadian variations of serum cortisol and tumour marker antigens. This we
      did in 33 cancer patients (13 breast cancer patients and 20 ovarian cancer
      patients). The profiles of serum cortisol were documented, since this hormone is
      considered as a strong marker of circadian rhythms. This study shows that 8 out
      of 13 breast cancer patients and 15 out of 20 ovarian cancer patients had deeply
      altered cortisol circadian patterns. The modifications were either high levels
      along the 24 h scale and/or erratic peaks and troughs and/or flattened profiles.
      Within 24 h, variations of tumour marker antigens as large as 70% were observed
      but no typical individual circadian patterns could be found. No relationship
      between cortisol subgroups and concentration of tumour marker antigens at 8 h
      could be observed (Kolmogorov-Smirnov's test). The question thus arises as to the
      origin of these alterations, and whether they are related to a cause or a
      consequence of the disease, and their possible incidence upon therapeutic
      designs.

PMID- 8883413
TI  - Prognostic significance of epidermal growth factor receptor in laryngeal squamous
      cell carcinoma.
AB  - Epidermal growth factor receptor (EGFR) content was determined by a radioligand
      receptor assay in 140 primary laryngeal squamous cell carcinomas (median value of
      8.4 fmol mg-1 protein, range 0-169.9 fmol mg-1 protein). Cox univariate
      regression analysis using EGFR as a continuous variable showed that EGFR levels
      are directly associated with the risk of death (chi 2 = 14.56, P-value = 0.0001)
      and relapse (chi 2 = 7.77, P-value = 0.0053). A significant relationship between
      EGFR status and survival was observed at the different arbitrary cut-off values
      chosen (8, 16 and 20 fmol mg-1 protein). The cut-off value of 20 fmol mg-1
      protein was the best prognostic discriminator. In fact, the 5 year survival was
      81% for patients with EGFR- tumours compared with 25% for patients with EGFR+
      tumours (P < 0.0001). The 5 year relapse-free survival was 77% for patients with
      EGFR- tumours compared with 24% for patients with EGFR+ tumours (P < 0.010). When
      clinicopathological parameters and EGFR status were examined in the multivariate
      analysis, T classification and EGFR status retained an independent prognostic
      value. In this study we demonstrated that high EGFR levels single out patients
      with poor prognosis in laryngeal cancer.

PMID- 8883414
TI  - bcl-2 overexpression combined with p53 protein accumulation correlates with
      hormone-refractory prostate cancer.
AB  - Seventy-seven men with histologically proven and newly diagnosed prostate cancer
      we investigated for the presence of bcl-2 protein overexpression and p53 protein
      accumulation 1 immunohistochemistry. Forty-five men had evidence of locally
      advanced and metastatic disease and we treated by means of hormone manipulation.
      Twenty-eight patients either failed to respond to initial hormone manipulation or
      relapsed within 37 months from diagnosis (median 20 months). Of the 77 cancers,
      37 (48% showed bcl-2 overexpression at diagnosis. Twenty-seven of those were
      treated with androgen ablation and 2 (74%) had hormone-refractory disease (P =
      0.0128). Twenty-three of 77 men (29.8%) had nuclear staining for p53 protein.
      Twenty-one of those were treated with hormone manipulation and 14 (66.6%) showed
      hormone resistance (P = 0.0012). Seventeen patients had both bcl-2 overexpression
      and p53 protein accumulation, 16 of whom were hormonally treated, with 13 (81.2%)
      having hormone-refractory disease (P < 0.0001). These findings suggest that the
      combined detection of p53 protein accumulation and bcl-2 overexpression may be
      useful in predicting hormone resistance in prostate cancer. By deregulating
      programmed cell death, alteration in these genes may prevent patients from
      responding to androgen ablation, or allow them to escape hormonal control of the
      disease.

PMID- 8883415
TI  - mdm2 gene mediates the expression of mdr1 gene and P-glycoprotein in a human
      glioblastoma cell line.
AB  - The overexpression of the multidrug resistance (mdr1) gene and its product, P
      glycoprotein (P-gp), is thought to limit the successful chemotherapy of human
      tumours. The mechanism by which mdr1 gene and P-gp are overexpressed in human
      tumours, however, is not yet clear. In this report, we show that the mdm2 (murine
      double minute 2) gene induced the expression of the mdr1 gene and P-gp in human
      glioblastoma U87-MG cells, which did not express the MDM2 protein or P-gp. The
      mdm2 gene, in addition, conferred the resistance of U87-MG cells to the apoptotic
      cell death induced by etoposide (VP-16) or doxorubicin. Furthermore, treatment
      with mdm2 antisense oligonucleotides inhibited the expression of P-gp in MDM2
      expressing U87-MG cells. These findings suggest that the mdm2 gene may play an
      important role in the development of MDR phenotype in human tumours.

PMID- 8883416
TI  - Expression of p21 (WAF1/CIP1) protein in clinical thyroid tissues.
AB  - p21 (WAF1/CIP1) protein expression in various thyroid tissues, including thyroid
      carcinoma, was studied by means of immunohistochemistry using anti-p21 monoclonal
      antibody. Normal follicles and hyperplasias rarely expressed p21, whereas
      immunohistochemically positive cells were also too rarely found in follicular
      adenomas to justify these cases being classified as positive. Twenty eight of the
      93 carcinomas examined (30.1%), however, were positive for p21. Of the p21
      positive cases, 80% of the undifferentiated and 28.6% of the poorly
      differentiated carcinomas showed lesions co-expressing p21 and p53. If diffuse
      immunoreactivity of p53 reflects the p53 mutation, our results indicate that p21
      in these carcinomas can be induced by p53-independent as well as by p53-dependent
      pathways. On the other hand, well-differentiated carcinomas did not co-express
      these two proteins and it therefore remains unclear whether p53-independent or
      p53-dependent pathways are predominant in this type of carcinoma. The incidence
      of expression of p21 was very similar in undifferentiated (26.3%), poorly (28.0%)
      and well-differentiated carcinomas (32.7%), even though they are characterised by
      different degree of malignancy. Furthermore, no correlation between p21
      expression and either clinical parameters or patient's prognosis could be
      established. These results suggest that p21 is only marginally related to the
      characteristics of thyroid carcinoma and can play only an adjuvant role in
      regulating the progression of this carcinoma.

PMID- 8883417
TI  - Emotional support for cancer patients: what do patients really want?
AB  - For many cancer patients and their families the experience of cancer is an
      intensely stressful one. Emotional support is important for most cancer patients
      during their illness and can be gained from different people and services. This
      study evaluates patients' attitudes to different sources of support and rates
      their satisfaction with sources already used. A total of 431 patients completed a
      questionnaire covering the use of different sources, including individuals,
      support groups and information sources. The questionnaire also incorporated
      validated measurements of anxiety, depression and locus of control. The results
      revealed that the three most important sources of emotional support were senior
      registrars (73%) and family (73%), followed by consultants (63%). Patients would
      prefer doctor- and nurse-led support groups to patient only-led groups (26% vs
      12%). Pamphlets, such as the BACUP booklets, proved the most important of the
      informational sources sought (50%). A total of 86% of patients were satisfied or
      very satisfied with the emotional support received. Patients who expressed
      dissatisfaction with their emotional support were significantly more likely to be
      anxious and depressed (P < 0.001). Patients who used information sources were
      more likely to have a higher locus of control over the course of their disease.
      These results show how important the doctor's role is in the provision of
      emotional support.

PMID- 8883418
TI  - Advances in the management of metastatic non-seminomatous germ cell tumours
      during the cisplatin era: a single-institution experience.
AB  - Long-term outcome was reviewed in 266 consecutive patients with metastatic non
      seminomatous germ cell tumours treated at a single institution. The overall 3
      year survival was 77%, and 3 year progression-free survival was 71%. Multivariate
      analysis identified the following clinical features as independent prognostic
      factors: the presence of liver, bone or brain metastasis, serum human chorionic
      gonadotropin > or = 10000 U l-1 and/or alpha-fetoprotein > or = 1000 ng ml-1, a
      mediastinal mass > 5 cm and the presence of 20 or more lung metastases. Age was
      not of prognostic significance. Patients without any of the above poor-risk
      factors had a 3 year survival of 91% regardless of etoposide- or vinblastine
      containing chemotherapy compared with 61% for the remaining patients. However,
      etoposide-containing protocols led to significantly improved survival in patients
      with at least one poor risk factor. After 612 patient-years of observation no
      case of secondary leukaemia was observed among 119 surviving patients who had
      received etoposide as part of their treatment. With a median follow-up of 93
      months, five patients developed a second germ cell tumour, two patients nongerm
      cell malignancies. Fourteen patients relapsed after a disease-free interval of
      more than 2 years, and nine patients died more than 5 years after commencement of
      treatment underscoring the need to report long-term results. There is some
      evidence that cumulative experience translates into improved survival and cure
      rates for patients with poor-risk metastatic disease.

PMID- 8883419
TI  - Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase
      inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal
      women with breast cancer.
AB  - The effect of anastrozole ('Arimidex', ZD1033), a new, selective, non-steroidal
      aromatase inhibitor on in vivo aromatisation and plasma oestrogen levels was
      evaluated in post-menopausal women with breast cancer. Twelve patients
      progressing after treatment with tamoxifen were randomised to receive anastrozole
      1 mg or 10 mg once daily for a 28 day period in a double-blinded crossover
      design. In vivo aromatisation and plasma oestrogen levels were determined before
      commencing treatment and at the end of each 4-week period. Treatment with
      anastrozole 1 and 10 mg reduced the percentage aromatisation from 2.25% to 0.074%
      and 0.043% (mean suppression of 96.7% and 98.1% from baseline) and suppressed
      plasma levels of oestrone, oestradiol and oestrone sulphate by > or = 86.5%, > or
      = 83.5% and > or = 93.5% respectively, irrespective of dose. Notably, several
      patients had their oestrone and oestradiol values suppressed beneath the
      sensitivity limit of the assays. In conclusion, anastrozole was found to be
      highly effective in inhibiting in vivo aromatisation with no difference in
      efficacy between the two drug doses. Contrary to previous studies on other
      aromatase inhibitors, this study revealed an internal consistency between the
      percentage aromatase inhibition and suppression of plasma oestrone sulphate.

PMID- 8883420
TI  - A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without
      cyclophosphamide pretreatment for the active specific immunotherapy of breast
      cancer.
AB  - Studies in animal models of mouse mammary carcinoma have shown that ovine
      submaxillary mucin, which carries multiple sialyl-Tn (STn) epitopes, is effective
      in stimulating an immune response and inhibiting tumour growth. In similar
      studies using carbohydrate antigens, pretreatment with low-dose cyclophosphamide
      has been shown to be important in modulating the immune response to antigen
      possibly by inhibiting suppresser T-cell activity. In a clinical trial assessing
      the efficacy and toxicity of synthetic STn, patients with metastatic breast
      cancer were randomised to receive 100 micrograms STn linked to keyhole limpet
      haemocyanin (KLH) with DETOX-B adjuvant given by subcutaneous injection at weeks
      0, 2, 5 and 9 with or without low-dose cyclophosphamide (CTX, 300 mg m-2)
      pretreatment, 3 days before the start of immunotherapy. Patients with responding
      or stable disease after the first four injections were eligible to receive STn
      KLH at 4 week intervals. The main toxicity noted was the development of
      subcutaneous granulomata at injection sites. Of 23 patients randomised, 18
      received four injections, 5 patients having developed progressive disease during
      the initial 12 week period. Two minor responses were noted in the 18 patients who
      received four active specific immunotherapy (ASI) injections and a further five
      patients had stable disease. Six patients continued ASI at 4 week intervals and a
      partial response was noted in a patient who had previously had stable disease.
      All patients developed IgG and IgM responses to sialyl-Tn and levels of IgM
      antibodies were significantly higher in those patients who were pretreated with
      CTX. Measurable tumour responses have been recorded following ASI with STn-KLH
      plus DETOX and the immunomodulatory properties of low-dose CTX have been
      confirmed.

PMID- 8883421
TI  - Plasma nitrate plus nitrite changes during continuous intravenous infusion
      interleukin 2.
AB  - Nitric oxide (NO), a biologically active mediator generated in many cell types by
      the enzyme NO synthase, may play an important role in cardiovascular toxicity
      that is frequently observed in cancer patients during intravenous (i.v.)
      interleukin 2 (IL-2) therapy. The induction of NO synthase and the production of
      NO seem to be involved in the pathogenesis of the vascular leakage syndrome, as
      well as in the regulation of myocardial contractility. In the present study, we
      evaluated the pattern of plasmatic NO changes during multiple cycles of
      continuous i.v. infusion (CIVI) of IL-2 in ten advanced cancer patients (five
      males, five females, median age 59 years, range 33-67 years; eight affected by
      renal cell cancer and two affected by malignant melanoma). The patients received
      IL-2 at 18 MIU m-2 day-1 (14 cycles) or 9 MIU m-2 day-1 (seven cycles) for 96 h,
      repeated every 3 weeks. Interferon alpha (IFN alpha) was also administered
      subcutaneously (s.c) during the 3 week interval between IL-2 cycles. For each
      cycle, plasma samples were collected before treatment (t0), 24 h (t1), 48 h (t2),
      72 h (t3) and 96 h (t4) after the start of IL-2 infusion, and 24 h after the end
      of the cycle. NO concentration was determined spectrophotometrically by measuring
      the accumulation of both nitrite and nitrate (after reduction to nitrite). The
      following observations may be drawn from data analysis: (1) plasma nitrate +
      nitrite significantly raised during treatment (P = 0.0226 for t0 vs t3), but
      statistical significance was retained only when cycles administered with IL-2 18
      MIU m-2 day-1 are considered (P = 0.0329 for t0 vs t3; P = 0.0354 for t0 vs t2 vs
      t4) (dose-dependent pattern); (2) during subsequent cycles a significant trend
      toward a progressive increase of plasma nitrate + nitrite levels, with increasing
      cumulative dose of IL-2, was observed (linear regression coefficient r = 0.62, P
      = 0.0141 for t0; r = 0.80, P = 0.0003 for t1; r = 0.62, P = 0.013 for t2; r =
      0.69, P = 0.045 for t3); (3) plasma nitrate + nitrite levels peaked earlier in
      subsequent cycles than in the first cycle; (4) all patients experienced
      hypotension. The mean of the systolic blood pressure values was significantly
      lower at the time of plasma nitrate + nitrite peak than at t0 (P = 0.0004); (5)
      the two cases of grade III hypotension occurred in patients with the higher mean
      and peak plasma nitrate + nitrite values. We conclude that determination of
      plasma nitrate + nitrite levels during CIVI IL-2 can usefully estimate, in a dose
      dependent pattern, the degree of peripheral vascular relaxation and capillary
      leakage associated with cytokine action, clinically manifested as hypotension.
      However, isolated cardiac toxicity that continues to represent a relevant problem
      during IL-2 therapy, does not appear to correlate with plasma nitrate + nitrite
      levels; therefore, further studies are required to understand adequately the
      mechanisms underlying IL-2-induced cardiac toxicity.

PMID- 8883423
TI  - Non-melanoma skin cancer and solar keratoses II analytical results of the South
      Wales Skin Cancer Study.
AB  - This study aimed to identify risk markers for prevalent solar keratoses (SKs) and
      squamous cell carcinomata (SCC) combined, for incident SKs and for spontaneous
      remission of SKs and to evaluate primary preventative measures. It was a cross
      sectional study, with follow-up, conducted in South Wales, and involved 1034
      subjects aged 60 years and over. The main outcome measures were the presence of
      and changes in SKs, and presence of skin cancers, on sun-exposed skin, and risk
      factors for prevalent SKs/SCCs and for incidence and remission of SKs. We found
      that variables independently associated with prevalent SKs/SCCs were: age [80 +
      years vs 60-64 years, odds ratio (OR) 3.7]; sex (male vs female OR 2.2);
      cumulative sun exposure (top quintile vs bottom quintile OR 3.3) and skin type
      (skin type 1 vs 4 OR 12.4). Use of sunscreen or protective clothing was not
      protective after controlling for confounders. Males and those who sunbathe
      infrequently showed greater remission of SKs. Older subjects and those spending
      most time in the sun in the preceeding 2 years were most likely to develop new
      SKs. We conclude that the risk factors identified are consistent with results
      from sunnier countries. The failure of sunscreen or clothing to emerge as
      protective raises doubts as to whether these measures are as effective in routine
      use in the general population as theoretical considerations and the limited trial
      evidence would predict. Recently reported sun exposure appears to influence the
      risk of developing new SKs.

PMID- 8883422
TI  - Non-melanoma skin cancer and solar keratoses. I. Methods and descriptive results
      of the South Wales Skin Cancer Study.
AB  - This study aimed to describe the prevalence and incidence of solar keratoses and
      skin cancers and the natural history of solar keratoses in a random population
      sample. It was a cross-sectional study, with follow-up, conducted in South Wales,
      and involved 1034 subjects aged 60 years and over drawn from the Family Health
      Services Authority register. The main outcome measures were detection of the
      presence of solar keratoses and skin cancers on sun-exposed skin and photographic
      validation of solar keratoses and biopsy confirmation of cancers wherever
      possible. We found that solar keratosis prevalence was 23% (95% confidence
      interval 19.5-26.5) and that of skin cancer (all types) 2% (95% confidence
      interval 1.0-3.5). The incidence rate of solar keratoses was 149 lesions per 1000
      person-years and of non-melanoma skin cancer 9 per 1000 person-years. In all 21%
      (95% CL 16-26) of solar keratoses regressed spontaneously during follow-up. None
      underwent malignant change. We believe that the failure of individuals to seek
      medical advice and the variable under-registration of non-melanoma skin cancer
      makes population-based study important. The high prevalence and incidence of
      malignant and pre-malignant skin lesions in this random sample raise major public
      health concerns. The high rate of spontaneous regression of solar keratoses and
      the low rate of malignant change challenges conventional views about the need for
      routine treatment of these lesions.

PMID- 8883424
TI  - Cigarette smoking and urinary oestrogen excretion in premenopausal and post
      menopausal women.
AB  - Cigarette smoking is associated with a reduction in the risk for endometrial
      cancer in post-menopausal women and it has been suggested that this is because
      smoking has an anti-oestrogenic effect. To investigate this, concentrations of
      oestrone, oestradiol and oestriol were measured in 24 h urine samples from 167
      premenopausal women (53 smokers, 114 non-smokers) and 200 post-menopausal women
      (54 smokers, 146 non-smokers). Among premenopausal women there were no
      significant differences in oestrogen excretion between smokers and non-smokers.
      Among post-menopausal women, geometric mean excretion rates for oestrone and
      oestradiol did not differ significantly between groups, but oestriol excretion
      was 19% lower (95% confidence interval -34% to -1%) in smokers than in non
      smokers. This may partly explain the reduced risk for endometrial cancer among
      post-menopausal smokers.

PMID- 8883425
TI  - Multistage designs for phase II clinical trials: statistical issues in cancer
      research.
AB  - The main objective of phase II clinical trials is to estimate treatment efficacy
      on a relatively small number of patients in order to decide whether the treatment
      ought to be studied in large-scale comparative trials. They play a key role in
      the drug development process, since the results determine whether or not to
      proceed to phase III trials. Multistage designs for phase II clinical trials
      proposed by Gehan, Fleming, Simon and Ensign are described and compared. Gehan's
      and Simon's designs have two stages, Fleming's designs can have two or more
      stages, and Ensign's three-stage design combines the first stage of Gehan with
      the two stages of Simon. Phase II clinical trial protocols and reports should
      include a description of the design selected with a justification for the
      particular choice. The present practice is very far from this ideal.

PMID- 8883426
TI  - Incidence of invasive cancers following carcinoma in situ of the cervix.
AB  - Women with carcinoma in situ (CIS) of the cervix uteri, notified to the
      population-based Cancer Registry of the Swiss Canton of Vaud between 1974 and
      1993, were actively followed up to 31 December 1993 for the occurrence of
      subsequent invasive neoplasms. Among 2190 incident cases of CIS, followed for a
      total of 22,225 person-years, 95 metachronous cancers were observed vs 77.9
      expected, corresponding to a significant standardised incidence ratio (SIR) of
      1.2. Ten cases of invasive cervical cancer were observed vs 3.0 expected (SIR =
      3.4, P < 0.01), the excess being larger in the first 10 years since CIS
      diagnosis. A total of 11 cases of four major tobacco-related sites (lung, mouth
      or pharynx, oesophagus and urinary bladder) were observed vs 5.1 expected,
      corresponding to a significant SIR of 2.2. The excess was observed > or = 10
      years after CIS diagnosis. There was also an excess of non-melanomatous skin
      cancers (29 observed, 16.9 expected, SIR = 1.7; P < 0.01), but not of skin
      melanoma and of any of the other neoplasms considered, including breast and
      corpus uteri. This population-based study, therefore, finds an excess of invasive
      cervical cancer in the short term after CIS diagnosis, and a medium- to long-term
      excess risk of tobacco-related and non-melanomatous skin neoplasms. These
      findings are discussed in terms of increased surveillance and case ascertainment
      after CIS, and of potential shared risk factors (tobacco and/or viral
      infections).

PMID- 8883427
TI  - Angiogenesis: a critical process in the pathogenesis of RA--a role for VEGF?

PMID- 8883428
TI  - What do general practitioners expect from rheumatology clinics?

PMID- 8883429
TI  - Margaret Holroyd Prize Essay. A patient-centred approach to evaluation and
      treatment in rheumatoid arthritis: the development of a clinical tool to measure
      patient-perceived handicap.
AB  - Assessment of patient-centered outcomes is of particular importance in a chronic
      disease such as rheumatoid arthritis (RA), where a major aim of treatment is a
      reduction of its disabling and handicapping effects. Rheumatology is reasonably
      well advanced in its deployment of such outcomes. Measurement of the patient's
      experience of disease has focused on the ability to perform daily living tasks
      and, latterly, on the more global effect on quality of life. Neither of these
      approaches is without conceptual and measurement problems. A new measure of
      patient-centred outcome in RA has been developed (Carr AJ, Br J Rheumatol
      1994;33:378-82). This tool, the Disease Repercussion Profile (DRP), attempts to
      extend the measurement of outcome to incorporate the individual functional,
      social, psychological, emotional and economic disadvantage resulting from RA,
      i.e. patient-perceived handicap. It has been designed for use as a clinical tool,
      to allow patients to specify the problems and needs of most importance to them,
      and as such represents a new approach. This paper reviews the development of the
      DRP in the context of existing health status measures and examines its potential
      role as a routine measure in an out-patient setting.

PMID- 8883430
TI  - Oncoprotein expression in human synovial tissue: an immunohistochemical study of
      different types of arthritis.
AB  - Based on the fact that synovial lining cells have some properties of transformed
      appearing cells, we have examined the expression of Myc, Myb, Fos, Jun and Ras
      oncoproteins in synovial tissues from patients with different types of arthritis.
      Formalin-fixed and paraffin-embedded sections of synovial tissue from 12 patients
      with rheumatoid arthritis (RA), 14 with reactive arthritis (ReA), nine with other
      seronegative arthritis (OSA), seven with bacterial arthritis (BA), eight with
      probable bacterial arthritis (PBA) and eight with osteoarthritis (OA) were
      studied using the immunoperoxidase staining technique. The oncoproteins studied
      were expressed both in the synovial lining layer and in the sublining layer,
      consisting of lymphocytes, other inflammatory cells and blood vessels. Among the
      six disease entities, RA and OA appeared to be the most distinct, whereas the
      results obtained for ReA and OSA, and on the other hand for BA and PBA, closely
      resembled each other. The expression of Myc, Myb, Fos and Jun was significantly
      correlated both to the degree of synovial hypercellularity and the synovial
      lymphocytic infiltration. For Ras, such a correlation could not be seen. We
      conclude that we find no evidence of a cell lineage-specific or a disease
      specific abnormality of proto-oncogene products in RA, and the expression of
      these oncoproteins is consistent with inflammation rather than with any primary
      abnormality of cell growth.

PMID- 8883431
TI  - Osteolytic properties of the synovial-like tissue from aseptically failed joint
      prostheses.
AB  - Relationships were found between the bone-resorbing ability of conditioned media
      (CMs) from culture of peri-prosthetic tissues and their levels of bone
      remodelling agents. Bone-resorbing activity was measured by 45Ca release from pre
      labelled mouse calvaria and 23 of 40 CMs exhibited bone-resorbing activity.
      Cytokine and prostanoid levels in the CMs were measured by immunoassay, and the
      levels of interleukin (IL)-1 beta, IL-6, tumour necrosis factor alpha (TNF alpha)
      and prostaglandin E2 (PGE2) correlated with each other, except for the latter
      two. Significantly higher levels of IL-6 were present in those CMs with bone
      resorbing activity than in those without, and a similar pattern was observed for
      PGE2 and IL-1 beta. However, some CMs with high levels of IL-1 beta, IL-6, TNF
      alpha and PGE2 failed to induce resorption, whereas a few CMs with low levels of
      these agents induced resorption. Moreover, neither dialysis of CMs nor addition
      of neutralizing antisera to IL-1 alpha and IL-1 beta to CMs, either alone or in
      combination, reduced the bone-resorbing activity of the CMs. It is considered
      that these agents may act synergistically to mediate osteolysis around failed
      joint implants, but that other unidentified bone-resorbing agent(s) must be
      involved.

PMID- 8883432
TI  - The relevance of chondroitin and keratan sulphate markers in normal and arthritic
      synovial fluid.
AB  - This study investigated the synovial fluid concentrations of glycosaminoglycan
      (GAG), keratan sulphate (KS) epitope 5D4 and chondroitin sulphate (CS) sulphation
      patterns in healthy volunteers and patients with osteoarthritis (OA) and
      rheumatoid arthritis (RA). Synovial fluids were collected from knee joints of
      healthy volunteers (n = 24), and patients with OA (n = 28) and RA (n = 29).
      Concentrations of GAG and the keratan sulphate epitope 5D4 were measured in 15 of
      the healthy volunteers, and all of the OA and RA synovial fluids. Total GAG was
      measured using a dye-binding method and 5D4 by an ELISA. The unsaturated CS
      disaccharides delta C4 and delta C6 were measured by capillary electrophoresis in
      all synovial fluids. The concentrations of GAG, 5D4 and delta C6 in the normal
      synovial fluid were higher but that of delta C4 lower than those of the disease
      groups. The delta C6:delta C4 ratios correlated with age (r = -0.437, P < 0.001)
      and the mean value was lower in females than males (2.92 compared with 5.22, P <
      0.001). After allowing for age and sex, the delta C6:delta C4 ratio in the
      control group was significantly elevated (P < 0.001) compared to both OA and RA.
      The ratio was also related to proteoglycan markers (r = 0.383 for 5D4 and r =
      0.357 for GAG). The finding that 5D4 and delta C6:delta C4 ratios are higher in
      synovial fluid from healthy volunteers compared to OA and RA suggests that they
      may be markers of the susceptibility of articular cartilage to early damage in
      arthritis.

PMID- 8883433
TI  - Antineutrophil cytoplasmic antibodies, abnormal angiograms and pathological
      findings in polyarteritis nodosa and Churg-Strauss syndrome: indications for the
      classification of vasculitides of the polyarteritis Nodosa Group.
AB  - The present study attempted to define the clinical, radiological, immunological
      and pathological characteristics of microscopic polyangiitis (MPA), and to
      separate them from classic PAN (c-PAN) and Churg-Strauss syndrome (CSS). In most
      cases, patients presenting microaneurysms and/or multiple vessel stenoses, which
      reflect medium-sized vessel involvement, did not have antineutrophil cytoplasmic
      antibodies (ANCA) (6.6%). Conversely, patients with glomerulonephritis almost
      never had abnormal angiograms. Furthermore, the clinical characteristics of ANCA
      positive patients also indicate small-sized vessel involvement. Skin involvement
      (73.1 vs 26.7%, P < or = 0.05), glomerulonephritis (38.5 vs 0%, P < or = 0.001)
      and the presence of ANCA (34.6 vs 6.7%, P < or = 0.05) were significantly more
      frequent in patients with normal than abnormal angiograms, respectively.
      Conversely, hypertension (66.7 vs 23.1%, P < or = 0.02), renal vasculitis (46.7
      vs 0%, P < or = 0.001) and hepatitis B antigenaemia (60 vs 11.5%, P < or = 0.01)
      were significantly more common in patients with abnormal angiograms.
      Stratification of patients according to vessel size showed that, except for skin
      involvement (P < or = 0.05) and glomerulonephritis (P < or = 0.01), which are
      direct manifestations of small-sized vessel diseases, clinical symptoms of PAN or
      CSS, angiographic findings and ANCA were not correlated to arteriole size.
      Although at present it is not possible to separate definitively MPA from c-PAN,
      our results show that ANCA should be considered diagnostic for MPA and, in most
      cases, should be an exclusion criterion for c-PAN. Conversely, small-sized vessel
      involvement can be observed in patients presenting characteristics of c-PAN, MPA
      or CSS and, therefore, is not a sufficient criterion for assigning diagnosis.

PMID- 8883434
TI  - Quantitative assessment of the synovial membrane in the rheumatoid wrist: an
      easily obtained MRI score reflects the synovial volume.
AB  - Determination of the synovial membrane volume in the rheumatoid arthritis (RA)
      wrist by gadolinium-DTPA-enhanced MRI is introduced. Moreover, dynamic imaging
      and an MRI score of synovial hypertrophy, based on gradings in six regions, are
      evaluated as substitutes of the time-consuming volume calculations. Twenty-six RA
      wrists were examined. Synovial membrane volumes ranged from 1 to 20 ml (median 9
      ml). Synovial hypertrophy scores were highly correlated to synovial volumes
      (Spearman r = 0.88; P < 10(-8) for uncorrelated values). The volumes and scores
      were significantly higher in wrists with joint swelling and/or joint tenderness
      than in wrists without these signs (Mann-Whitney, both P < 0.05). Suboptimal
      slice selection made dynamic imaging uninformative. MRI allows quantification of
      the synovial volume in the rheumatoid wrist. The volume is related to clinical
      signs of inflammation, but may also give information about the cumulated synovial
      proliferation in the joint. An easily obtained score of synovial hypertrophy
      reflects the synovial volume and may thus be a useful marker of synovial
      involvement.

PMID- 8883435
TI  - Parotid gland ultrasonography as a diagnostic tool in primary Sjogren's syndrome.
AB  - The diagnostic value of parotid gland ultrasonography (Acuson 128, 7 MHz
      transducer) was studied in 62 patients with primary Sjogren's syndrome (SS) and
      in 69 controls of similar age and sex distribution. Different degrees (mild,
      evident or gross) of parenchymal inhomogeneity (PIH) were the most important
      sonographic changes in SS; they occurred in 83.9% of the patients. The
      sonographic results (the presence or absence of PIH) were in accordance with the
      parotid sialographic and scintigraphic findings and the histology of the minor
      salivary glands in 87.3, 84.7 and 84.3% of the cases, respectively. Of the
      degrees of PIH, only evident and gross PIH are thought to be of true diagnostic
      value for SS. On the basis of the good agreement between the sonographic and
      sialographic results, consideration of the introduction of parotid sonography as
      an alternative to sialography is suggested in SS if the latter method cannot be
      performed.

PMID- 8883436
TI  - Bronchoalveolar lavage in mixed cryoglobulinaemia associated with hepatitis C
      virus.
AB  - In order to evaluate the presence of an inflammatory process of the lower
      respiratory tract in patients with mixed cryoglobulinaemia (MC) associated with
      hepatitis C virus (HCV), bronchoalveolar lavage (BAL) was performed in 16 non
      smoking females free of clinical pulmonary symptoms and with normal chest
      roentgenograms. Pulmonary function tests including diffusion capacity for carbon
      monoxide (DLCO) were also carried out. Thirteen healthy subjects were evaluated
      as the control group. Patients with MC had a lower percentage of alveolar
      macrophages (75% vs 92%, P = 0.001) and a higher percentage of lymphocytes (19.7%
      vs 7%, P = 0.001) than healthy controls. The percentage of CD3+ lymphocytes was
      higher in MC patients than in controls (86.5% vs 70%, P = 0.004). No significant
      differences in the percentage of CD4+, CD8+ and CD19+ lymphocytes, neutrophils
      and eosinophils were found. Pulmonary function tests showed significantly lower
      values of forced expiratory flow (FEF) 25-75 (P = 0.05) and DLCO (P = 0.05) in MC
      patients than in healthy controls. No correlations between BAL results and
      pulmonary function tests were found. The 5 yr follow-up of five patients did not
      demonstrate deterioration in lung function. Thus, BAL results indicate a
      subclinical T-lymphocytic alveolitis in MC HCV+ patients that is not associated
      with a risk of deterioration in lung function.

PMID- 8883437
TI  - Left ventricular function in scleroderma.
AB  - Scleroderma affects the left heart directly and indirectly via the effects of
      systemic hypertension. Using transthoracic echocardiography, we evaluated 35
      patients with scleroderma and compared them with matched control subjects.
      Compared with controls, there were no differences between left ventricular
      dimensions, wall thickness, calculated mass or fractional shortening. However,
      the left atrium was enlarged (P = 0.006) and the mitral deceleration time was
      prolonged (P = 0.0005) in patients with scleroderma; suggesting abnormal
      diastolic function. After adjusting for potential confounders, duration of
      Raynaud's was found to be an independent predictor of deceleration time (P =
      0.04), E/A peak velocity ratio (P = 0.04), A peak velocity (P = 0.004) and A
      velocity time integral (P = 0.0001), all measures of diastolic function. This
      group of individuals with scleroderma have evidence of abnormal diastolic
      function of the left ventricle despite normal left ventricular size and systolic
      function, and in the absence of hypertrophy. This finding is independent of the
      use of vasoactive medications and history of systemic hypertension, and thus may
      be due to primary myocardial involvement by scleroderma. The tendency to abnormal
      diastolic function of the left ventricle correlated with the duration of
      Raynaud's phenomenon.

PMID- 8883438
TI  - Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients.
AB  - A retrospective chart review was carried out on 344 patients with systemic
      sclerosis (SSc) followed prospectively for the occurrence of pulmonary
      hypertension (PHT). Seventeen patients (4.9%) were found to have PHT. Eight
      patients had isolated PHT, while in nine PHT was associated with restrictive lung
      disease (RLD). The subset with RLD developed PHT earlier, but had longer survival
      than patients with isolated PHT. Patients with limited scleroderma tend to
      develop isolated PHT, while in those with diffuse disease PHT is associated with
      RLD. Irrespective of disease type, PHT in SSc has an extremely poor prognosis
      with a median survival of 12 months following diagnosis.

PMID- 8883440
TI  - An approach to therapeutic trials in rheumatology: the foundation for applied
      rheumatology research.

PMID- 8883439
TI  - A comparison of the clinical features of hospital out-patients with rheumatoid
      disease and osteoarthritis in Pakistan and England.
AB  - Several studies have demonstrated differences between ethnic groups in the
      severity and pattern of rheumatoid arthritis (RA) and osteoarthritis (OA). The
      current investigation compared RA and OA in Pakistani and British White Caucasian
      out-patients in two teaching hospitals. There were 88 RA patients in each
      setting, matched for age, gender and disease duration. The pattern of OA was
      sought by recording the details of 44 consecutive new referrals to each clinic.
      Amongst the RA patients, joint deformity and tenderness were similar, but
      disability was more severe, ESR higher, anaemia more pronounced and RA latex more
      often positive amongst the Pakistani patients. X-ray damage was more pronounced
      amongst the British patients, especially in the feet. The British were also more
      likely to have rheumatoid nodules and to have undergone disease-modifying
      treatment or joint surgery. The paradox of more severe indices of disease
      activity and disability with less X-ray erosion in hands and feet might be
      explained by the impact of treatment on joint inflammation and the beneficial
      influence of surgery on disability in the British. The worse X-ray scores in the
      White Caucasians might indicate a genetic predisposition to radiologically more
      severe disease. The age of the British OA patients was significantly higher, but
      this is unlikely to have influenced the striking disparity in the frequency of
      isolated knee OA, which was significantly greater in the Pakistani patients.
      Comparison with age- and sex-matched healthy Pakistani subjects suggested that
      susceptibility to knee OA was strongly associated with body weight, but not with
      knee bending at prayer or with joint laxity. Amongst the Pakistanis, Heberden
      nodes, hip involvement and evidence of generalized OA were significantly less,
      but these observations may have been due to their younger age. The study
      confirmed differences in the clinical presentation of both RA and OA amongst
      patients in Pakistan compared with White Caucasians in Britain. Several
      confounding factors, such as patient recruitment, culture, treatment and age, may
      have influenced the results, but it remains likely that genetic factors are
      important.

PMID- 8883441
TI  - Ultraviolet irradiation in systemic lupus erythematosus: friend or foe?
AB  - The long established notion that UV irradiation is always harmful to patients
      with systemic lupus erythematosus has been challenged by some recent reports of
      benefit using a form of phototherapy with UV-A1. In the review we discuss the
      different types of UV radiation, the links between certain forms of such
      radiation and clinical manifestations and consider the mechanisms involved.

PMID- 8883442
TI  - Mycobacterium xenopi--an unusual presentation as tenosynovitis of the wrist in an
      immunocompetent patient.
AB  - Mycobacterium xenopi is an atypical acid-fast bacillus which may colonize tap
      water supplies. It typically causes pulmonary infection, particularly in patients
      with pre-existing lung damage, and non-pulmonary involvement is rare. We describe
      the first reported case of tenosynovitis due to this organism in an
      immunocompetent male patient.

PMID- 8883443
TI  - Paget's disease in a patient with ankylosing spondylitis--a diagnostic dilemma.
AB  - A patient is described in whom the diagnosis of Paget's disease was complicated
      by the presence of ankylosing spondylitis. The mechanism for the unusual
      distribution of pagetic bone is discussed.

PMID- 8883444
TI  - Pattern of joint involvement in children with Lyme arthritis.
AB  - Following the clinical observation of a peculiar joint pattern in children with
      Lyme arthritis, we classified the pattern of joint involvement in children with
      oligoarticular arthritis (2-4 joints) of different causes, including Lyme
      arthritis, juvenile chronic arthritis and juvenile spondyloarthropathy, as: (1)
      symmetrical: arthritis of the same joints on both sides of the body; (2)
      unilateral: all involved joints on the same side; (3) predominantly unilateral:
      joints involved on the contralateral side also showed ipsilateral involvement;
      (4) oblique: involvement on the contralateral side of one or more joints that did
      not show ipsilateral involvement. The oblique pattern was found in 13 of 42
      children with early-onset pauciarticular juvenile chronic arthritis and in 17 of
      32 patients with juvenile spondyloarthropathy, but not in 32 of 32 children with
      Lyme arthritis. If confirmed, these results may have implications for the
      diagnosis and pathogenesis of Lyme arthritis.

PMID- 8883445
TI  - Chronic recurrent multifocal osteomyelitis: spinal involvement and radiological
      appearances.
AB  - We report a case of chronic recurrent multifocal osteomyelitis which presented as
      back pain in a 14-yr-old male. The full distribution of the spinal lesions was
      determined by MRI, which proved to be more sensitive than other imaging
      modalities. After 1 yr, in spite of a good symptomatic response to corticosteroid
      therapy, new MRI abnormalities had developed.

PMID- 8883446
TI  - Back pain in children.
AB  - Pay attention to back pain reported by children. Half will have a specific or
      serious cause, the presenting symptoms of serious conditions may be misleadingly
      mild, and the spectrum of causes and mode of presentation differ from adults.
      Warning features include onset aged < 4 yr, symptoms persisting beyond 4 weeks,
      interference with function, systemic features, worsening pain, neurological
      features and recent onset of scoliosis. Scintigraphy is often useful where
      clinical features and plain radiographs fail to identify the diagnosis. Sports
      activities may cause stress reactions in the immature spine, particularly at the
      junction between spinal segments of differing mobility, the vascularity of the
      disc and vertebra predisposes to infection, spinal tumours presenting as pain
      tend to be primary and benign, congenital spinal anomalies causing pain tend to
      present in childhood, spondylitis presents differently from adults, and
      conversion hysteria, typically presenting with gross, bizarre and disabling
      symptoms, is not uncommon in adolescent girls.

PMID- 8883447
TI  - Failure of first-line therapy with intravenous immunoglobulin in a child with
      scleromyositis.

PMID- 8883448
TI  - Methotrexate treatment every other week in patients with juvenile chronic
      arthritis.

PMID- 8883449
TI  - Folate supplementation and methotrexate.

PMID- 8883450
TI  - Are antineutrophil cytoplasmic antibodies associated with spondyloarthropathies?

PMID- 8883451
TI  - Phenytoin-induced pseudo-Sjogren's syndrome.

PMID- 8883452
TI  - Cervical spondylodiscitis in a patient with ankylosing spondylitis.

PMID- 8883454
TI  - One small step at a time.

PMID- 8883453
TI  - Magnetic resonance imaging and pathologic studies on lateral fluid percussion
      injury as a model of focal brain injury in rats.
AB  - In this study, morphologic changes in brain lesions initiated by moderate lateral
      fluid percussion injury in rats were investigated chronologically using high
      resolution magnetic resonance imaging (MRI) and histopathologic methods. Rats
      were subjected to moderate fluid percussion injury (average 2.80 +/- 0.48
      atmospheres) over the exposed dura overlying the right parietal cortex. MRI
      obtained in vivo were compared with corresponding pathologic findings at 1, 6,
      and 24 h and at 3, 6, 14 and 80 days after injury. T2-weighted images showed
      scattered low-signal intensity in the injured cortex within a few hours after
      injury, whereas histologic findings revealed intraparenchymal hemorrhages. T2
      weighted images of the ipsilateral cerebral cortex and/or corpus callosum showed
      a high-signal-intensity area 4 h after injury. The high-signal-intensity area
      became largest in size between 6 and 24 h, then declined gradually, and almost
      disappeared 14 days after injury. Histologic examination revealed pyknosis,
      retraction of the cell body of neurons with vacuolated neuropil in the
      corresponding regions 6 and 24 h after injury, and cystic necrosis 14 days after
      injury. The location and extent of these pathologic changes were depicted
      accurately by MRI in vivo. In the hippocampus, pyknosis and retraction of the
      cell body of pyramidal neurons were observed on the injured side 24 h after
      injury, and the number of neurons in the CA1 and CA2-CA3 regions decreased
      significantly on the same side by 14 days after injury. It is concluded that
      morphologic changes in the brain following experimental traumatic brain injury in
      rats are detectable in vivo by high-resolution MRI, and that MRI may be useful
      for the evaluation of treatment effects in experimental brain injury.

PMID- 8883455
TI  - Medical savings accounts and research.

PMID- 8883456
TI  - The demographic face of America's elderly.

PMID- 8883457
TI  - How will medical savings accounts affect medical spending?
AB  - This paper estimates that if a cross-section of nonelderly adults switched from
      comprehensive insurance to a combination of catastrophic insurance and a medical
      savings account (MSA), they would reduce their medical spending by between 2% and
      8%. The author constructs measures of the prices individuals pay for medical care
      under a typical comprehensive insurance policy and a particular combination of
      catastrophic insurance and MSA. The difference in prices paid in the two health
      plans is combined with price elasticity estimates from the Health Insurance
      Experiment to predict changes in spending. Several qualifications to the estimate
      are considered.

PMID- 8883458
TI  - Patient choice of physician: do health insurance and physician characteristics
      matter?
AB  - Generous health insurance coverage is widely believed to have contributed to both
      high and rising health care costs. This paper tests the hypothesis that better
      insured patients will demand higher "quality" by choosing more often to visit
      specialists rather than generalist physicians. We model the conditional decision
      to seek care from a specialist physician as a function of health insurance
      status, physician characteristics, and other socioeconomic factors. Analysis of
      data from the 1987 National Medical Expenditure Survey and the American Medical
      Association suggests that the presence of insurance coverage does not affect
      choice of physician. The results do show that people enrolled in health
      maintenance organizations (HMOs) see specialists less often than other patients.

PMID- 8883459
TI  - The effect of maternal substance abuse on the cost of neonatal care.
AB  - This study addresses the effect of maternal substance abuse on the cost of
      neonatal care in a sample of all singleton live births in Maryland in 1991. Most
      other cost studies have analyzed data from only one hospital; we analyzed data
      from 54 hospitals and therefore can control for individual hospital effects and
      correlation of observations within hospitals. We find that maternal drug abuse
      has a significant positive effect on total hospital charges, length of stay, and
      average daily charges, with the increase in length of stay being proportionally
      greater than the increase in average daily charges. Maternal alcohol abuse also
      has a positive effect on hospital charges and length of stay, but the effects are
      not statistically significant. About half the effect of drug abuse on total
      charges works indirectly through premature birth and other comorbidities.

PMID- 8883460
TI  - Does risk-adjusted readmission rate provide valid information on hospital
      quality?
AB  - The purpose of this study was to determine whether readmission rates, adjusted to
      account for differences in clinical characteristics of patients treated, provide
      valid information on hospital quality of care. Twelve clinical conditions were
      selected. Condition-specific models to predict readmission risk were estimated
      using Medicare UB-82 claims data. These models then were used to calculate
      readmission risk probabilities for patients whose medical records had been
      reviewed for quality of care by a Medicare peer review organization. I
      hypothesized that patients who received poor quality care during a
      hospitalization episode would be more likely to be readmitted after discharge
      than those who received acceptable quality care. My analysis found no support for
      this hypothesis. In each of the 12 clinical conditions studied, readmission rates
      of cases that received poor quality care were essentially the same as those whose
      care was judged acceptable. This was true both for readmission rates that were
      adjusted for patients' demographic and clinical characteristics, and for
      unadjusted rates, such as those typically displayed in hospital report cards.

PMID- 8883461
TI  - The effect of rural hospital closures on the financial performance of neighboring
      rural hospitals.
AB  - This study investigates how the closure of rural hospitals affected other rural
      hospitals. The empirical analysis examined whether being the neighbor of a closed
      rural hospital affected financial performance variables during the periods before
      and after closure. Before and after comparisons of surviving rural hospitals were
      made between 1985 and 1989 for closures in 1987 and between 1986 and 1990 for
      closures in 1988. The regression results showed that neighbors of closed rural
      hospitals typically did experience increased volume in comparison to non
      neighbors, but the increased volume did not lead to reductions in average cost or
      to improved profitability, after controlling for other factors.

PMID- 8883462
TI  - Bundling post-acute care (PAC) with Medicare DRG payments: an exploration of the
      distributional and risk consequences.
AB  - This exploratory study simulates the distributional and risk consequences of
      bundling 60 days' worth of post-hospital, post-acute care (PAC) with the
      inpatient stay, and paying for both on an all-inclusive, single-free basis.
      Simulations are conducted using 1987-1988 Medicare claims data from five states,
      focusing on patients discharged in 14 PAC-intensive diagnosis-related groups
      (DRGs). In this data, we find that hospital-level risk actually would be reduced
      if post-acute care were bundled with the DRG payments for inpatient stays.

PMID- 8883463
TI  - Pluripotential liver stem cells: facultative stem cells located in the biliary
      tree.
AB  - The ability of the liver to regenerate after parenchymal damage is usually
      accomplished by the ephemeral entry of normally proliferatively quiescent (G0)
      hepatocytes into the cell cycle. However, when hepatocyte regeneration is
      defective, arborizing ductules which are continuous with the biliary tree,
      proliferate and migrate into the surrounding parenchyma. In man these biliary
      cells have variously been referred to as ductular structures, neoductules and
      neocholangioles, and have been observed in many forms of chronic liver disease,
      including cancer. In experimental animals similar ductal cells are usually called
      oval cells, and their association with defective regeneration has led to the
      belief that these cells represent a progenitor cell population. Oval cells are
      thought to take over the burden of regenerative growth after substantial
      hepatocyte loss, suggesting that they are the progeny of facultative stem cells.
      The liver is not, however, generally considered as a stem cell-fed hierarchy,
      although this is disputed by others. Despite this, the subject of oval cells has
      aroused intense interest as these cells may represent a target population for
      hepatic carcinogens, and they may be useful vehicles for ex vivo gene therapy.
      This review proposes that the liver does harbour stem cells which are located
      throughout the biliary epithelium, and that oval cells represent the progeny of
      these stem cells and function as an amplification compartment for the generation
      of 'new' hepatocytes. This is a conditional process which only occurs when the
      regenerative capacity of hepatocytes is overwhelmed and thus, unlike the
      intestinal epithelium, the liver is not behaving as a classical continually
      renewing stem cell-fed lineage. We focus on the biliary network, not merely as a
      conduit for bile, but also as a cell compartment with the potential to
      proliferate under appropriate conditions and give rise to fully differentiated
      hepatocytes and other cell types.

PMID- 8883464
TI  - c-erbB-2/neu protein expression, DNA ploidy and S phase in breast cancer.
AB  - DNA content and c-erbB2/neu protein (p185) expression were evaluated by flow
      cytometry and ELISA, respectively, in 166 specimens of primary breast cancer. A
      non-diploid DNA content was found in 88 tumours (53%), with the DNA index ranging
      from 0.7-2.7. S phase fraction (SPF) evaluation, performed in 130 cases, showed
      significantly higher values in aneuploid than in diploid tumours (median values,
      17.3% and 5.8%, respectively). Thirty-six tumours (21.6%) showed p185
      overexpression, while 45 (27.1%) and 85 (51.3%) showed intermediate and low
      expression, respectively. A good correlation (P = 0.0023) was found between DNA
      content and p185 positivity. Tumours with high p185 values were mainly aneuploid,
      while tumours with intermediate or low expression had variable degrees of DNA
      content. Furthermore, p185 concentration was significantly higher in aneuploid
      than in diploid tumours (P = 0.009). The highest rate of p185 (+) cases and the
      highest p185 concentrations occurred in triploid (1.3 < D.I. < or = 1.7),
      compared to the other tumours. SPF values and p185 positivity rates were not
      significantly correlated in diploid and in aneuploid tumours.

PMID- 8883465
TI  - Monoclonal antibodies Ki-S3 and Ki-S5 yield new data on the 'Ki-67' proteins.
AB  - The monoclonal antibody (mab) Ki-67 has been used for about 10 years, mainly in
      tissue sections, to monitor proliferating cells, but so far only very little is
      known about the proteins it recognizes. The new mabs Ki-S3 and Ki-S5 detect
      proliferating cells in frozen and paraffin-embedded tissues. They recognize
      proteins with the same molecular mass as Ki-67 in Western blot and for the first
      time also in immunoprecipitation experiments. With these mabs we were able to
      enrich and purify the Ki-67 proteins. Protein sequencing of four peptides of the
      digested proteins corresponded to the cDNA-deduced amino acid sequence already
      published for the Ki-67 proteins. Since we were able to immunoprecipitate the Ki
      67 proteins, we performed various immunoprecipitation experiments to obtain more
      information about the nature of these proteins. After radiolabelling L428 cells
      with [35S]-methionine we were able to immunoprecipitate the Ki-67 proteins after
      only 5 min of labelling time. In turnover experiments the Ki-67 proteins could
      not be detected 3 h after the end of labelling. These data indicate a half-life
      of the Ki-67 proteins of about 90 min. Labelling experiments with [32P]
      orthophosphate revealed that the Ki-67 proteins are phosphorylated. After
      dephosphorylation was blocked with okadaic acid or cell growth was arrested by
      means of Colcemid, the phosphorylation of the Ki-67 proteins was greatly
      increased, indicating that the Ki-67 proteins are phosphorylated via serine and
      threonine, and that the phosphorylation of the Ki-67 proteins increases in
      cycling cells. Labelling experiments with [3H]-mannose and [3H]-glucose revealed
      that the protein is weakly N-glycosylated.

PMID- 8883466
TI  - Probing chromatin structure in the early phases of apoptosis.
AB  - A typical flow cytometric marker of apoptosis is the appearance of a hypodiploid
      peak. This phenomenon is related to the chromatin fragmentation and loss that
      occurs during the late stages of the process. We describe herein the changes
      occurring at the chromatin level in purified nuclei preparations obtained from
      human peripheral blood mononuclear cells in a time-course study, including the
      simultaneous evaluation of nuclear proteins and DNA stainability, light
      scattering properties, and spectrophotometric determination of the protein
      content. An augmentation of fluoroscein isothiocyanate (FITC) stainability was
      noticed as early as 1 h after irradiation. As this phenomenon is not correlated
      to changes in actual protein content, one can conclude that modifications of
      basic protein accessibility occur from the early phases of the apoptotic process.
      Also DNA stainability augmented with time, generating the transient appearance of
      a hyperdiploid peak that preceded the appearance of the hypodiploid peak typical
      of the late stages of the process, and that shared with the latter the same light
      scattering properties. Chromatin status was further explored by staining
      apoptotic nuclei using DNA probes with peculiar molecular weight. Propidium
      iodide (PI) and ethidium bromide (EB), but not the much bulkier 7
      aminoactinomycin D (7-AAD), identified the nuclei with a transient increase in
      DNA stainability confirming that an increased dye accessibility to binding sites
      was responsible for the phenomenon. Remarkably, all dyes identified the same
      proportion of hypodiploid nuclei when an apoptotic nucleus shed its fragmented
      chromatin. Control experiments included differential interference contrast and
      fluorescence microscopy that showed the purity of nuclei preparations and the
      typical morphological apoptotic features. Finally, the simultaneous evaluation of
      DNA by PI and nuclear proteins by FITC in a time course study allowed a thorough
      assessment of changes occurring at the chromatin level in the diverse stages of
      apoptosis. It is suggested that proteolysis precedes endonucleolysis and probably
      renders it easier the final endonucleolytic step leading to DNA fragmentation and
      loss.

PMID- 8883467
TI  - Modulation of the biological effects of glucosinolates by inulin and oat fibre in
      gnotobiotic rats inoculated with a human whole faecal flora.
AB  - The influence of dietary fibre on the biological effects of glucosinolates was
      investigated in gnotobiotic rats harbouring a human whole faecal flora. Animals
      were fed for 6 wk with diets containing 12% rapeseed meal (RSM) supplemented or
      not supplemented with 10% inulin (INL) or oat fibre. Both fibre types enhanced
      the liver hypertrophy due to RSM to equal extents, but had different effects on
      the other glucosinolate-related toxic effects. INL partially restored a normal
      thyroid hormone status whereas kidney weight, goitre and growth deficit were
      increased on exposure to the diet containing oat fibre. Oat fibre and, to a
      lesser extent, INL modulated the alterations of digestive xenobiotic-metabolizing
      enzymes (XME) induced by RSM. They counter-balanced the induction of hepatic
      cytochrome P-450 and lessened the induction of uridine diphosphate
      glucuronosyltransferase in the liver but did not modify depletion of its activity
      in the small intestine. On the other hand, they enhanced the induction of
      glutathione S-transferase in the liver and the large intestine but not in the
      small intestine. These findings give new evidence that the biological effects of
      naturally occurring non-nutrient compounds are closely dependent on the
      composition of the diet. Two mechanisms are proposed to explain the different
      influence of INL and oat fibre on RSM toxicity. Their different fermentative
      characteristics could lead to a modulation of the bacterial metabolism of
      glucosinolates in the caecum. Alternatively, their own action on the digestive
      XME could modify the subsequent metabolism of bacterial glucosinolate
      derivatives.

PMID- 8883469
TI  - Long-term toxicity/carcinogenicity study of L-histidine monohydrochloride in F344
      rats.
AB  - The long-term toxicity and carcinogenicity of histidine, an essential amino acid
      for most animal species, were examined in Fischer 344 (F344) rats. Groups of 50
      males and 50 females were given L-histidine monohydrochloride (HMHC) in their
      diet at concentrations of 0 (control), 1.25 and 2.5% for 104 wk; these dose
      levels were selected on the basis of the results of a subchronic toxicity study,
      in which body weights were depressed and formation of sperm granulomas in the
      epididymis was histologically evident in males fed 5.0% HMHC. All surviving rats
      were killed at wk 107. Increases in red blood cell count, haemoglobin value and
      haematocrit level were observed in male rats given 2.5% HMHC. A variety of
      tumours developed in all groups, including the control group, but all the
      neoplastic lesions were histologically similar to those known to occur
      spontaneously in this strain of rats, and no statistically significant increase
      in the incidence of any tumor was found in the treated groups of either sex.
      Thus, it was concluded that, under the present experimental conditions, HMHC is
      not carcinogenic in F344 rats.

PMID- 8883468
TI  - A 90-day feeding study of the alkaloids of Lupinus angustifolius in the rat.
AB  - Groups of 20 Sprague-Dawley rats of each sex were fed diets containing lupin
      alkaloid at dose levels of 0, 100, 330, 1000 and 5000 ppm supplemented with
      maltodextrin to attain a level of 4.5%, for 13 wk (equivalent to average daily
      intakes of lupin alkaloid of approximately 0, 10, 30, 100 and 500 mg/kg body
      weight/day, respectively, over the course of the study). A further group of rats
      was fed control (basal) diet over the same period. All control and high-dose
      animals underwent an ophthalmological examination before the start of the study
      and before autopsy. Blood samples were collected from all rats prior to the start
      of treatment, during wk 6 and prior to autopsy for haematological and clinical
      chemistry examination. All animals were monitored daily for change in clinical
      condition, and body weight and food intake were measured twice weekly. A range of
      tissues were preserved for histological examination at autopsy. There was an
      initial drop in food intake by all rats in the 1000 and 5000 ppm groups and
      thereafter the intake was between 90% and 95% of that of the controls. In
      general, no other effects related to treatment were seen. On the basis of the
      lower body weights and food intakes of the groups fed the alkaloid at levels of
      1000 and 5000 ppm, a no-observed-adverse-effect level (NOAEL) of 330 ppm is seen
      under the conditions of this study. It is likely that these effects are entirely
      due to the antipalatability effect of the lupin alkaloids. In view of the growth
      rates, haematology, clinical chemistry and histological findings, a speculative
      NOAEL of 1000 ppm may be more appropriate.

PMID- 8883471
TI  - Developmental toxicity of concanavalin A in rats: association with restricted
      migration of neural crest cells.
AB  - Concanavalin A (Con A), a plant lectin, was injected iv into pregnant rats as a
      single dose of 5, 10 or 20 mg/kg on gestational day (GD) 8, to investigate
      developmental toxicity in foetuses at term and to examine histologically embryos
      between GD 10 and 12. There were high incidences of various malformations in the
      10 and 20 mg/kg groups: externally, craniofacial dysplasia and closure defects of
      the ventral body wall; internally, anophthalmia and cardiovascular malformations;
      and in the skeleton, anomalies of the anterior region of the vertebrae and ribs.
      Histological examination revealed that neural crest cells (NCC) in the control
      embryos appeared to be streaming from the neural crest towards the ventral region
      on GD 10, 11 and 12, and reached the region of the branchial arches on GD 12. By
      contrast, those in the Con A-treated embryos were aggregated near the dorsal
      region on GD 10 and 11, and had not reached the destination even on GD 12. These
      findings suggest that pathogenesis of developmental toxicity of Con A in rats is
      associated with disturbance of NCC migration and inhibition of their
      pluripotentiality at the destination.

PMID- 8883470
TI  - Disposition of ingested olestra in weanling mini-pigs.
AB  - The disposition of ingested olestra in Hanford mini-pigs was examined by
      following a single oral gavage dose of radiolabelled (U-14C-sucrose) olestra
      Eight dosed animal (four/sex) and one undosed animal were killed 1, 3 and 7 days
      after dosing, and tissues were collected and counted. Urine and faeces were
      collected continuously and counted. Tissue lipids were extracted and analysed for
      intact radiolabelled olestra by size exclusion chromatography. Sucrose will be
      excreted in urine if olestra is absorbed and metabolized. Mean recovery of
      radiolabel was 96.6% of the administered dose. Of the recovered radiolabel, more
      than 99.4%, on average, was not absorbed and found in faeces, or cage and animal
      wash solutions. The absorbed radiolabel (0.6%), was distributed across the
      carcass, all tissues and blood, or excreted in urine. This radiolabel primarily
      came from the metabolism of glucose and fructose resulting from the hydrolysis of
      the trace levels of penta- and lower sucrose esters present in the test material.
      No radiolabel was found in the olestra-containing fraction of liver lipids, the
      primary measure of absorbed and non-metabolized olestra, at a detection limit of
      0.0002% of dose. A conservative estimate of the amount of 14C-sucrose excreted in
      the urine was 0.0012%. The total absorption of intact olestra was thus less than
      0.0014% of the dose, the sum of the two measures. These results indicate that
      intact olestra is essentially not absorbed by the weanling mini-pig, an animal
      with a young developing gastrointestinal tract similar to that of young children
      (2-5 yr).

PMID- 8883472
TI  - Subchronic toxicity of thiabendazole (TBZ) in ICR mice.
AB  - The subchronic toxic effects of thiabendazole (TBZ) administered in the diet at
      levels of 0 (control), 0.8 and 1.6% for 13 wk to male and female ICR mice were
      investigated. Mean body weights of male mice fed 0.8 or 1.6% TBZ showed a
      significant decrease compared with controls, except for wk 3 and 8 for mice fed
      0.8% TBZ. Red blood cell parameters in male mice of treated groups were
      significantly lower than controls. Biochemistry showed increased concentrations
      of GOT and GPT in male and female mice of the 1.6% TBZ groups. Relative spleen or
      liver weights were significantly increased in male and female mice of treated
      groups. Relative kidney weights of treated mice tended to be increased in
      comparison with controls. Histological findings showed a marked haemosiderosis
      and extramedullary haematopoiesis in the spleen of treated mice. In the liver,
      sinusoidal dilatation and enlargement of liver cells were found in treated mice.
      In the kidney, atrophy of tubules with peritubular fibrosis, cell infiltration
      and some tubular necrosis were found in treated mice. Slight hyperplasia was
      found in the urinary bladder of treated mice. The findings in the present study
      indicate that TBZ caused a slight anaemia and liver or kidney injury at both
      levels tested, under these conditions.

PMID- 8883473
TI  - Cytogenetic results from a chronic feeding study of MeIQx in mice.
AB  - The primary food mutagens found in cooked meat are the heterocyclic aromatic
      amines, including 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). High
      dose, acute exposures of MeIQx produce hepatic tumours in some mouse and rat
      strains. By assaying chromosome damage it may be possible to correlate
      aberrations with exposure to a mutagen. Whole chromosome painting by fluorescence
      in situ hybridization allows the rapid screening of metaphase chromosomes for
      rearrangements. This technique was applied to female mice (C57BL/6) chronically
      fed 100-400 ppms MeIQx for up to 6 months. Two tissues, blood and bone marrow,
      were screened with multicolour whole chromosome painting probes (1,2,3 and 8).
      The mice showed no outward signs of toxicity at any dose and very few chromosome
      aberrations were observed. A slight but significant increase in sister chromatid
      exchanges (SCE) was seen at 400 ppm in blood at 6 months. When MeIQx was removed
      from the diet for 1 month there was an apparent decline in SCEs only for animals
      previously given the 400 ppm diet.

PMID- 8883474
TI  - Effect of commercial marinades on the mutagenic activity, sensory quality and
      amount of heterocyclic amines in chicken grilled under different conditions.
AB  - The effect of processing conditions on the mutagenic activity and sensory quality
      of everyday food was studied by investigating grilled chicken samples seasoned
      with four different marinades and grilled at temperatures of about 110, 170 and
      220 degrees C. The amounts of the heterocyclic amines 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5
      f]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5,-b]pyridine were
      determined only in samples grilled at 220 degrees C, using a gas chromatography
      mass spectrometry technique with negative-ion chemical ionization. Sensory
      quality was determined using the extended ranking test method and the mutagenic
      activity using the Ames Salmonella assay. At 220 degrees C one of the marinades
      decreased the mutagenic activity in the chicken samples compared with the
      unseasoned control or samples treated with the other marinades. Great variations,
      without any clear correlation with mutagenicity, were observed in the amounts of
      heterocyclic amines between chicken samples treated with the same or different
      marinades. At the grilling temperatures of 170 degrees C and 110 degrees C the
      mutagenic activities of the chicken samples were lower or they were non
      mutagenic. There was no correlation between mutagenic activity and sensory
      quality of the products. The samples with high mutagenic activity were ranked to
      be as good as the samples with lower or no mutagenicity. The results show that it
      is possible to prepare grilled products with reduced mutagenicity without
      compromising their sensory quality. It was also evident that marinades can have a
      reducing effect on the mutagenicity of grilled chicken. Variation observed in the
      amounts of heterocyclic amines between equivalent products makes it difficult to
      estimate their concentration in everyday foods.

PMID- 8883475
TI  - In vitro percutaneous absorption of model compounds glyphosate and malathion from
      cotton fabric into and through human skin.
AB  - Chemicals are introduced to fabric at many steps during manufacture and use.
      Fabrics containing chemicals can cause medical problems such as dermatitis and
      death. Insecticides impregnated into uniforms worn by "Desert Storm" personnel
      are implicated in "Gulf War Syndrome'. These chemicals must get from fabric into
      and through skin to cause toxic effects. The objective of the present study was
      to determine in vitro percutaneous absorption of model chemicals glyphosate
      (water soluble) and malathion (relative water insoluble) from cotton fabric into
      and through human skin. The percutaneous absorption of glyphosate from water
      solution was 1.42 +/- 0.25% dose. This decreased to 0.74 +/- 0.26% for glyphosate
      added to cotton sheets and immediately put onto skin. If the cotton sheets were
      dried for 1 or 2 days, then applied to skin, absorption was 0.08 +/- 0.02% and
      0.08 +/- 0.01% respectively. However, wetting the 2-day dried cotton sheet with
      water to simulate sweating or wet conditions increased absorption to 0.36 +/-
      0.07%. Similar results were found for malathion. Absorption of malathion from
      aqueous ethanol solution was 8.77 +/- 1.43%. This decreased to 3.92 +/- 0.49%,
      0.62 +/- 0.11% and 0.60 +/- 0.14% for 0, 1- and 2-day-treated cotton sheets.
      However, malathion absorption from 2-day treated/dried cotton sheets increased to
      7.34 +/- 0.61% when wetted with aqueous ethanol. These results show that
      chemicals in fabric (clothing, rug, upholstery, etc.) can transfer from fabric
      into and through human skin to cause toxic effects.

PMID- 8883476
TI  - Comparison of low-volume, Draize and in vitro eye irritation test data. I.
      Hydroalcoholic formulations.
AB  - The first phase in a series of investigations of the relationship between low
      volume eye test (LVET) data, Draize eye irritation test data, and comparable data
      from 25 in vitro assay protocols is presented. These investigations utilize
      Draize eye test and in vitro assay data generated previously as part of the
      Cosmetic, Toiletry and Fragrance Association (CTFA) Evaluation of Alternatives
      Program. LVET data were generated de novo using the same 10 representative
      hydroalcoholic personal-care formulations. The linear correlation between maximum
      average score (MAS) as determined by the Draize test and the LVET (LVET-MAS) was
      0.93. Comparison of in vitro assay performance with that of the LVET was
      determined by statistical analysis of the relationship between LVET-MAS and in
      vitro endpoint. As in the CTFA program, regression modelling is the primary means
      of enabling such a comparison. The objective is to predict LVET-MAS for a given
      test material (and to place upper and lower prediction interval bounds in the
      range in which the LVET-MAS is anticipated to fall with high probability)
      conditional on observing an in vitro assay score for that material. The degree of
      confidence in prediction is quantified in terms of the relative widths of
      prediction intervals constructed about the fitted regression curves. Four assays
      [EYTEX MPA (membrane partition assay), HET-CAM (hen's egg test-chorioallantoic
      membrane HET-CAM) I, neutral red release and HET-CAM II] were shown to have the
      greatest agreement with the LVET. These assays were also among those with low
      discordance rates relative to the Draize test. Prediction of LVET-MAS values from
      experimentally determined in vitro scores was more accurate for hydroalcoholic
      formulations with lower rather than higher irritancy potential.

PMID- 8883477
TI  - Lack of transforming activity of fumonisin B1 in BALB/3T3 A31-1-1 mouse embryo
      cells.
AB  - The capacity of fumonisin B1 (FB1) to induce morphological transformation of
      cultured mammalian cells was assessed using BALB/3T3 A31-1-1 mouse embryo cells.
      FB1 with 90% purity was prepared from Fusarium proliferatum grown on whole corn.
      Cell growth was not inhibited by 48 hr of exposure at concentrations up to 1000
      micrograms/ml. Moderate inhibition was induced by 6 days of exposure. In
      transformation assays with a 48-hr exposure, increases in transformed foci were
      observed at some concentrations; however, the responses were not reproducible.
      Prolonged exposure for up to 4 wk at 10, 100 and 500 micrograms/ml failed to
      induce increases in transformed foci. Analysis of combined results showed that
      only the increase induced by a 48-hr exposure at 500 micrograms/ml was
      significant. A trend test indicated the lack of a dose response for
      concentrations of 10-1000 micrograms/ml. FB1 seems to lack in vitro transforming
      activity.

PMID- 8883478
TI  - Fluorine intake of a Tibetan population.
AB  - Measurements of food consumption of randomly selected families and fluorine
      levels in food and beverages were used to calculate the fluorine intake of
      Tibetan people living in nomadic or semi-nomadic areas of the region and
      regularly consuming brick tea both as a beverage and in food. The fluorine intake
      of these groups (children 5.49-7.62 mg day; adults 10.43-14.48 mg/day) was much
      higher than that of members of a Han population living in the region (children
      1.44 mg/day; adults 2.54 mg/day). The amounts of fluorine consumed by the Tibetan
      inhabitants are at least twice the WHO suggested limit (2 mg/day). Tea plants are
      rich in fluorine, and the highest levels are found in older leaves which are used
      to make brick tea. We conclude that brick tea is the major source of fluorine
      intake by the Tibetan population studied.

PMID- 8883479
TI  - The influence of gender, expectancy, and partner beverage selection on
      (meta)perceptions in a "blind" dating situation.
AB  - There is little question that alcohol plays a role in social situations. Most of
      the research in this area has used a paradigm designed to understand the effects
      of consuming alcohol on anxiety and social behavior. Most of the previous studies
      have looked only at situational factors-with limited focus on personality
      variables, using confederates to control the social reaction that participants
      received, with drinking generally occurring in a solitary situation. In the
      present study we were interested in understanding the interpersonal nature of
      reactions to alcohol consumption. The focus of this study was on the stimulus
      value of alcohol rather than anticipated or pharmacological effects of alcohol
      consumption. In large groups, individuals completed cognitive-personality
      measures assessing typical alcohol consumption, alcohol expectancies, and social
      anxiety. In the second part of the study, participants were paired with a member
      of the opposite sex with whom they had no previous contact: perceptions of their
      partner and metaperceptions were assessed after 4 and 15 minutes (before and
      after choosing a beverage--beer, soft drinks, etc.). Results indicate that
      positive alcohol expectancies interact with partner alcohol selection in
      predicting changes in metaperceptions of friendliness and relaxation. With
      friendliness, this result was most pronounced in men. These results are discussed
      in terms of the role alcohol expectancies may play in filtering alcohol relevant
      environmental information, and the influence of positive alcohol expectancies in
      mixed-sex drinking situations.

PMID- 8883480
TI  - History of sexual abuse and obesity treatment outcome.
AB  - In this study, clinical data from 22 obese women who reported a history of sexual
      abuse were compared to clinical data from 22 obese women who denied a history of
      sexual abuse. Subjects were matched for body mass index (BMI), sex, and age. All
      subjects were enrolled in a multidisciplinary outpatient hospital-based very-low
      calorie diet (VLCD) weight-management program. Subjects completed a structured
      clinical interview, the Beck Depression Inventory (BDI), and the Weight Efficacy
      Life-Style Questionnaire (WEL). Subjects with a history of sexual abuse lost
      significantly less weight and reported more episodes of nonadherence. Possible
      explanations for these findings include both psychiatric distress and low weight
      self-efficacy. The difference between the groups in self-efficacy was greatest in
      situations involving negative affect or physical discomfort.

PMID- 8883481
TI  - Associations between drug use and deviant behavior in teenagers.
AB  - Confirmatory factor analyses of self-reports of drug use and deviant activity
      from 701 female and 662 male students in grade 10 revealed three correlated
      higher-order dimensions of behavior: alcohol use and sociability, rebelliousness,
      and deviant behavior, including drug use other than alcohol. The
      intercorrelations between these dimensions were 0.548 or higher for both male and
      female students, indicating an underlying unidimensionality of these activities.
      These results suggest that drug prevention programs that curb initial and regular
      use of the gateway drugs may have a broader, spillover impact on other deviant
      behavior. They also suggest that programs aimed at both deviance and drug use are
      worth pursuing and that schools are an important venue for identifying deviant
      youth. The strong links between alcohol use and sociability underline the need to
      counteract the social acceptability of drinking and focus on the social contexts
      in which it occurs.

PMID- 8883482
TI  - Psychometric evaluation of the Situational Confidence Questionnaire in
      adolescents: fitting a graded item response model.
AB  - Self-efficacy theory has been extensively applied to alcoholism treatment,
      theories of relapse, and relapse prevention. Most empirical studies of perceived
      self-efficacy to resist heavy drinking have used the Situational Confidence
      Questionnaire (SCQ). Among adults, this instrument has been shown to be
      psychometrically sound. Little is known, however, about the psychometric
      properties of the SCQ in the adolescent population. We administered the SCQ to a
      sample of 662 adolescents to evaluate its psychometric properties. Each of the
      eight subscales was found to be unidimensional. Invariance of the item parameters
      across different groups was also examined. The reliability coefficients, based on
      item response theory (marginal reliability) and classical measurement theory
      (Cronbach alpha), were found to be high. These results demonstrate that the SCQ
      is appropriate for use among adolescents.

PMID- 8883483
TI  - Concordance between urinalysis results and self-reported drug use by applicants
      for methadone maintenance in Australia.
AB  - This study examined concordance between self-reported drug use and urinalysis
      data among 341 applicants for methadone treatment in Sydney, Australia. Rates of
      under-reporting of use of specific drugs were low (0% to 10%). Irregular drug
      use, short half-life of some abused drugs, and relatively low sensitivity of the
      TLC assay procedure led to most detected drugs being found in only one of two
      urine samples collected. Subjects reported having recently used nearly twice as
      many drugs as were detected in their urine. Agreement (kappa) between self-report
      and urinalysis results was in the fair to good range for most drugs. None of the
      six predictors of misreporting examined were found to be of practical value.

PMID- 8883484
TI  - Addictive behavior of older adults.
AB  - Very little is known about addictive alcohol use by older people. In the present
      paper personal effects reasons for drinking (i.e. drinking for the effects of
      alcohol) and concerns about drinking were used as indicators of addictive
      drinking behavior among a sample of 826 people aged 65 and older who participated
      in survey interviews in their homes. The relationship of addictive drinking
      behavior to frequency of drinking, quantity of drinks per occasion, and
      depressant drug use was examined. Alcohol use was higher among males and young
      old (aged 65-74), while depressant medication use was higher among females and
      old-old (aged 75+). However, with the exception of use of over-the-counter
      medications containing codeine (which was significantly higher among current
      drinkers), no relationship existed between alcohol use and use of depressant
      medications. Personal effects reasons for drinking and concerns about drinking
      were related both to alcohol and depressant medication use. Frequency of drinking
      was associated with higher endorsement of both personal effects and social
      reasons, whereas volume of alcohol consumption (drinks per drinking day) was
      associated only with personal effects drinking. In addition, use of depressant
      medications by drinkers was significantly related to consuming alcohol for
      personal effects reasons (but unrelated to consuming for social reasons) and with
      having concerns about one's own drinking. These results suggest that even within
      the generally low levels of alcohol consumption of older people, addictive-use
      patterns emerge. In addition, the results confirm the importance of including
      depressant medication use in evaluating the drinking behavior of older people.

PMID- 8883485
TI  - Relationship of personal tobacco-raising, parental smoking, and other factors to
      tobacco use among adolescents living in a tobacco-producing region.
AB  - This study examined factors related to tobacco use among youth from tobacco
      raising (TRH) and nonraising households (NRH). The subjects were 3,851 seventh
      grade students from 19 middle schools located in a tobacco-raising region. Valid
      self-reports of tobacco use were encouraged by the use of a test for carbon
      monoxide in expired air. Cigarette use was higher when (a) at least one parent
      smoked, and/or (b) the student personally raised tobacco. A boy who personally
      raised tobacco and had at least one parent who smoked was 10.2 times more likely
      to have smoked in the last 7 days than a boy from a nonraising household in which
      neither parent smoked. For girls, the odds ratio was 5.6:1. Tobacco use among
      students in this high-risk group was higher than rates reported in national or
      regional studies. Other results were: (1) use began very early--16% of the
      students had tried cigarettes and 13% of the boys had tried smokeless tobacco
      (SLT) in Grade 3 or earlier; and (2) users reported more lenient rules at home
      regarding tobacco use than did nonusers. Years from now, these high-risk students
      are likely to be major contributors to increased morbidity and mortality due to
      tobacco use. Implications for tobacco prevention in tobacco-raising areas are
      discussed.

PMID- 8883486
TI  - Ethnicity and the effects of mapping-enhanced drug abuse counseling.
AB  - It was hypothesized that node-link mapping a tool for visually representing
      client issues during drug abuse counseling, would reduce communication barriers
      between counselors and their African American and Mexican American clients. Three
      hundred twenty daily opioid users participated in methadone maintenance treatment
      programs in three cities for 6 months or longer following random assignments to
      mapping-enhanced or standard counseling. Clients in the mapping condition had
      fewer drug-positive urines (with respect to opiates and cocaine), missed fewer
      scheduled counseling sessions, and were rated more positively by their counselors
      on rapport, motivation, and self-confidence during the first 6 months of
      treatment. Significant interactions involving ethnicity and counseling condition
      suggested that mapping is more effective for African Americans and Mexican
      Americans than for Whites. The use of mapping appears to help reduce cultural,
      racial, and class communication barriers by providing a visual supplement and a
      common language that enhances counselor-client interchanges.

PMID- 8883487
TI  - The development of a brief scale to measure outcome expectations of reduced
      consumption among excessive drinkers.
AB  - This paper describes the development of a brief scale to measure outcome
      expectations of reduced consumption among excessive drinkers (low dependence
      drinkers consuming more than recommended levels). This work, which forms part of
      a larger matching study of brief intervention, is based on the general
      proposition that outcome expectations of reduced consumption might be more
      important than previously thought for understanding and predicting behavior
      change. Twelve outcomes, derived from interviews with excessive drinkers, formed
      the basis of a questionnaire, the Excessive Drinker Outcome Expectations Scale
      (EDOES), which examined not only the valence of each outcome, but a comparison
      between expectations of reduced consumption versus drinking usual amounts. The
      questionnaire was administered to 235 hospitalized excessive drinkers. Principal
      components analysis produced two scales, reflecting the costs and benefits of
      change. The questionnaire proved to have acceptable levels of test-retest
      reliability and predictive validity. Analyses of construct validity revealed that
      outcome expectations of reduced consumption were increasingly positive across
      stages of change.

PMID- 8883488
TI  - Coping strategies and continued drug use among methadone maintenance patients.
AB  - Drug addiction has been conceived as a maladaptive means of coping utilized by
      individuals unable or unwilling to deal with stresses in more adaptive ways.
      Although a growing body of evidence supports the link between alcohol abuse and
      maladaptive coping styles, there is relatively little empirical support for the
      connection between maladaptive coping and other kinds of drug use. The present
      study employed a cross-sectional design to assess coping and drug use in a sample
      of 276 methadone maintenance patients. Structural equation modeling was used to
      assess the factor structure of the coping measure and the relationship between
      coping and unauthorized drug use. The results suggest that coping and drug use
      are related in this population and that this relationship is different for Black
      patients than for White patients.

PMID- 8883489
TI  - A comparison of factor structures of adolescent and adult alcohol effect
      expectancies.
AB  - A comparison of the factor structures of alcohol effect expectancies of adults
      (aged 18 and older) and adolescents (aged 12-17) was conducted. Data were from a
      nationally representative sample of United States residents. Two factors were
      extracted for the adults, and three for the adolescents. General positive and
      negative factors were common to each solution. In addition, the adolescent
      solution contained a factor related to alcohol-induced sexual enhancement. The
      pattern and magnitude of the loadings for the adult and adolescent negative
      factor were nearly identical, and the positive factors were very similar. Results
      are consistent with a two-factor model of alcohol expectancies among adults, with
      slightly more differentiated expectancies among adolescents.

PMID- 8883490
TI  - Contingency management for tobacco smoking in methadone-maintained opiate
      addicts.
AB  - Seventeen methadone-maintained cigarette smokers received 4 weeks of contingency
      management (CM) as a stop-smoking intervention. Results indicated that CM
      patients significantly reduced breath CO levels from baseline to completion of
      treatment and that 23.4% of patients maintained 1 week or more of continued
      smoking abstinence. Results indicated a link between smoking abstinence and
      reduced cocaine use, although not reduced opiate use, which raised questions
      about possible shared biological and psychological mechanisms for tobacco and
      cocaine use.

PMID- 8883491
TI  - Serum lipoproteins in children and young adults: determinants and treatment
      strategies.
AB  - Serum lipoproteins are related to vascular atherosclerotic changes as seen in
      necropsy studies of child fatal accident victims; therefore, efforts have been
      made to reveal the determinants of lipoprotein metabolism in children and young
      adults. Recent data emphasize the adverse effects of obesity, insulin resistance
      and high fat intake on lipid profiles of children, and currently many lifestyle
      and dietary intervention studies are in progress. Detection of hereditary
      dyslipidemias in childhood is presently hampered by diagnostic problems. However,
      with the advent of efficient tools for genetic mapping, early diagnosis of common
      genetic dyslipidemias will probably be possible in the near future.

PMID- 8883492
TI  - Plasma lipids and lipoprotein concentrations among American Indians: comparison
      with the US population.
AB  - Lipoprotein measurements from the Third National Health and Nutrition Education
      Survey were used to estimate the need to measure fasting lipid concentrations and
      offer dietary and drug interventions in the US population. In this review, we
      compare the distribution of the Third National Health and Nutrition Education
      Survey population (according to National Cholesterol Education Program
      guidelines) with a contemporary sample of lipoprotein measurements in 4549
      American Indians. Compared with data from the former, relatively fewer American
      Indians have cholesterol levels greater than 240 mg dl-1 and a much larger
      proportion have 'desirable' cholesterol levels less than 200 mg dl-1. The above
      guidelines, dictating measurement of fasting lipoprotein concentrations and
      dietary or drug intervention, take into account age, presence of cardiovascular
      risk factors and levels of both HDL- and LDL-cholesterol. The proportion of
      American Indians requiring these interventions is somewhat at less than the Third
      National Health and Nutrition Education Survey population, even though the
      American Indian population in this comparison is generally older (45-74 years of
      age) than the Survey participants (20 to more than 75 years of age). We review
      the literature concerning lipoprotein measurements in other American Indian and
      ethnic population groups that are undergoing rapid changes in lifestyle. In
      general, cardiovascular risk factors, including lipoprotein concentrations, are
      accumulating. These factors suggest that the public health impact of coronary
      heart disease will increase as these populations undergo further lifestyle
      changes.

PMID- 8883493
TI  - Coronary heart disease risks in Asian Indians.
AB  - An increased prevalence of coronary heart disease in Asian Indian both from the
      native country and the immigrant population has been known for some time. With
      around 15,000,000 Asian Indians living outside India including 1,500,000 in the
      UK and 1,000,000 in the US, various pathogenic factors have attracted great
      interest in the recent past. Prevention strategies have been recommended based on
      these findings. Insulin resistance, central obesity and lipid abnormalities such
      as high triglyceride levels, low HDL levels and high lipoprotein(a) levels have
      been documented. This predisposition to accelerated atherosclerosis is
      genetically determined but is being enhanced by change in lifestyle, or
      'westernization'. An increased prevalence of coronary heart disease because of
      these changes in lifestyle is seen in India itself, where differences are found
      between urban and rural populations. This tendency seems to be noticed early in
      life, and hence the need for early prevention strategies are discussed.

PMID- 8883494
TI  - Obesity and coronary heart disease.
AB  - Obesity carries a penalty of an associated adverse cardiovascular risk profile.
      Largely as a consequence of this, it is associated with an excess occurrence of
      cardiovascular disease morbidity and mortality. It is concluded on the basis of
      data from the Framingham study and other large prospective studies that the rate
      of development of cardiovascular disease rises rapidly in relation to even modest
      amounts of adiposity. The abdominal pattern of adiposity, and specifically
      visceral adiposity, appears to be the most hazardous. First identified as a cause
      of glucose intolerance, abdominal adiposity has been identified as promoting
      insulin resistance, hypertension and dyslipidemia, as well as CHD. While the
      impact of epidemic obesity on the health of white Americans is becoming more
      fully understood, there are important gaps in the knowledge about the nature of
      influence of adiposity on CHD in large subgroups of the population. The dearth of
      detailed and long term prospective studies of African-Americans is the most
      conspicuous shortcoming of the research base. Finally, because there is a great
      potential benefit of remaining lean or achieving a sustained weight loss when
      indicated, and given the high prevalence of obesity, research on adiposity
      prevention and more effective weight reduction methodology are urgently needed.

PMID- 8883495
TI  - Risk factors for cardiovascular disease among women.
AB  - The studies of risk factors for cardiovascular disease among women have changed
      over the past few years because of: (1) the further development and evaluation of
      noninvasive methods of measuring subclinical atherosclerosis, (2) the
      availability of potent drugs that substantially lower LDL-cholesterol levels, (3)
      improvement in the methods of measuring factors related to clotting and
      fibrinolysis and inflammation, (4) better methods of quantifying obesity, fatness
      and body fat distribution, (5) increasing interest in the interrelationship
      between endogenous sex-steroid hormone metabolism, risk factors and disease, (6)
      the relationship of new metabolic risk factors and cardiovascular disease and (7)
      the use of molecular genetics to identify specific genotypes of risk factors.

PMID- 8883496
TI  - Hypoalphalipoproteinemia (low high density lipoprotein) as a risk factor for
      coronary heart disease.
AB  - Low HDL levels are inversely related to risk for coronary heart disease. Several
      different mechanisms may account for this relationship. First, low HDL levels may
      be directly atherogenic; second, a low HDL often denotes high levels of other
      atherogenic lipoproteins (for example, remnants); and third, a low HDL frequently
      accompanies other coronary risk factors (for example, insulin resistance,
      diabetes, and raised blood pressure). This multiplicity of relationships probably
      explains the power of low HDL levels to predict acute coronary events.

PMID- 8883497
TI  - Insulin resistance and coronary heart disease.
AB  - Insulin resistance and hyperinsulinaemia often occur with many cardiovascular
      risk factors. Whether hyperinsulinaemia and insulin resistance are risk factors
      for coronary heart disease is still a matter of debate. The information from
      prospective population studies, in which the relationship between
      hyperinsulinaemia and coronary heart disease has been investigated, is
      summarized. The possibility that hyperinsulinaemia and insulin resistance
      increase the risk for coronary heart disease will be approached from two angles.
      Evidence is presented of how hyperinsulinaemia and insulin resistance increase
      the risk for coronary heart disease indirectly through their effects on
      cardiovascular risk factors. Finally, evidence of how hyperinsulinaemia and
      insulin resistance could directly promote atherosclerosis is reviewed.

PMID- 8883498
TI  - Does treatment of noninsulin-dependent diabetes mellitus reduce the risk of
      coronary heart disease?
AB  - Diabetes is an independent risk factor for the development of coronary heart
      disease and has a tremendous impact on mortality. In patients with noninsulin
      dependent diabetes mellitus, coronary heart disease is the leading cause of
      death. Both hyperinsulinemia and hyperglycemia have been suggested as risk
      factors for accelerated atherogenesis in diabetes. Whichever mechanism is
      implicated, a beneficial effect of therapy in preventing cardiovascular disease
      is a major requirement. Until now, it is not clear whether stringent control of
      blood glucose levels reduces the risk of development of coronary heart disease in
      patients with noninsulin-dependent diabetes mellitus. This review emphasizes the
      relative roles of insulin and glucose on coronary heart disease development in
      noninsulin-dependent diabetes mellitus. The different therapeutic options of
      pharmacological treatment in hyperglycemia in noninsulin-dependent diabetes
      mellitus are discussed, as well as their impact on coronary heart disease risk.

PMID- 8883499
TI  - Lipids and endothelial function: effects of lipid-lowering and other therapeutic
      interventions.
AB  - Coronary arteries are regulated by neuronal mechanisms, hormones and paracrine
      mediators. The importance of endothelium-dependent mechanisms has recently been
      recognized. The endothelium responds to mechanical and chemical signals from the
      blood by releasing mediators that modulate vascular tone and structure, platelet
      function, coagulation and monocyte adhesion. Important relaxing factors are
      nitric oxide, prostacyclin and a putative hyperpolarizing factor. Nitric oxide
      also inhibits smooth muscle proliferation and, together with prostacyclin,
      platelet function. Bradykinin-induced nitric oxide production is reduced by
      angiotensin-converting enzyme. Endothelin-1, thromboxane A2 and prostaglandin H2
      are contracting factors. Thromboxane A2 and prostaglandin H2 activate platelets,
      while endothelin has no direct platelet effects, but causes smooth muscle
      proliferation. In hypercholestermia, endothelium-dependent relaxation is impaired
      and contraction as well as adhesion of monocytes and platelets enhanced.
      Pharmacological correction of hyperlipidemia by statins also improves or
      normalizes endothelial dysfunction in patients. Angiotensin-converting enzyme
      inhibitors have similar effects.

PMID- 8883500
TI  - Hypertension, dyslipidemia, and insulin resistance: links in a chain or spokes on
      a wheel?
AB  - Rather than a link in a causal chain leading to hypertension, insulin resistance
      and resultant hyperinsulinemia may be 'spokes on a wheel', with central or
      visceral obesity as the postulated hub of the wheel. Hypertension,
      hypertriglyceridemia and high density lipoprotein cholesterol are depicted as
      other spokes. Newly identified metabolic pathways in adipose tissue or the
      modulating effects of various predisposing genes may lead to variable expression
      of various components of the multiple metabolic syndrome in individuals with a
      predisposition to the collection of visceral fat.

PMID- 8883501
TI  - Dyslipidemia in peripheral vascular disease.
AB  - Peripheral atherosclerosis (carotid and aortofemoral vascular districts) shows
      some peculiar characteristics with respect to coronary atherosclerosis. In this
      paper we have reviewed the most recent studies on the relationships between
      atherosclerosis of the limbs and lipid metabolism. Several authors have described
      increased plasma levels of lipoprotein remnants, lipoprotein (a) and some lipid
      peroxidation parameters in extracoronary atherosclerosis, while HDL (and their
      subfractions) seem to be reduced. Some of these modifications may be related to
      the direct metabolic effects of smoking and diabetes, which frequently coexist.
      Recent intervention trials show a possible regression of established
      atherosclerotic plaques after hypolipidemic therapy. This further underscores the
      role of plasma lipoprotein pattern in determining peripheral vascular lesions.

PMID- 8883502
TI  - Soy protein and serum lipids.
AB  - Evidence exists indicating that substitution of soy for animal protein reduces
      both total ahd LDL-cholesterol concentrations in humans. There are a number of
      biologically active compounds associated with soy protein; however, the precise
      mechanism and the component(s) of soy responsible have not been fully
      established. Some studies suggest that, when soy protein is fed, cholesterol
      absorption or bile acid reabsorption, or both, is impaired. This is observed in
      some animal species such as rabbits and rats but not in humans, nor when amino
      acids replace intact soy protein. Other workers have proposed that changes in
      endocrine status are responsible, however, this again has not been observed in
      humans. Increases in LDL receptor activity in both animals and humans have been
      reported after ingestion of soy protein or various extracts of soy, or both.
      Furthermore, the soybean isoflavone genistein may inhibit lesion and thrombus
      formation via inhibition of second messengers.

PMID- 8883504
TI  - Nutrition and therapeutics.

PMID- 8883503
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 8883505
TI  - Genetics and molecular biology.

PMID- 8883506
TI  - Lipid metabolism.

PMID- 8883507
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 8883508
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 8883509
TI  - Therapy and clinical trials.

PMID- 8883510
TI  - Information content and clarity of radiologists' reports for chest radiography.
AB  - RATIONALE AND OBJECTIVES: We systematically characterized the information
      provided by chest radiography reports on a nationally representative sample of
      822 elderly patients hospitalized in 297 acute-care hospitals in five states who
      had an admission diagnosis of congestive heart failure, acute myocardial
      infarction, or pneumonia. METHODS: We studied the content of radiography reports,
      including mention of the type or adequacy of radiography; the presence or absence
      of a prior radiograph; comments about bones, the aorta, the mediastinum, and
      pleura and notation of the laterality of findings; and the presence of diagnosis.
      Two physicians reviewed each patient's report, and a third assigned the final
      rating when they disagreed. RESULTS: Our analysis found wide variation in content
      of chest radiography reports, extensive variation in terms used to identify the
      presence or absence of abnormal findings, and a large degree of uncertainty in
      what was found. CONCLUSION: With most hospitals introducing new information
      systems in response to technological advances and the need to generate more
      formal hospitalwide reports, the time is right to improve the quality of chest
      radiography reporting.

PMID- 8883511
TI  - Assessment of renal function with computed tomographic densitometry measurements.
AB  - RATIONALE AND OBJECTIVES: We assessed the relationship between multiple renal
      computed tomographic (CT) densitometry parameters and renal function. METHODS:
      Three hundred seventy-three patients underwent standardized helical CT of the
      abdomen. The ratio of mean attenuation in the renal cortex to mean attenuation in
      the aorta (KAR), the products of mean renal cortical attenuation with CT
      estimated renal volume (KVP), and the patient's weight (KWP) were derived from
      scans obtained 90 sec (n = 373) and 30 sec (n = 108) after initiation of
      intravenous contrast material administration. These densitometry parameters were
      compared with renal function measured by serum level of creatinine and creatinine
      clearance (CrCl). RESULTS: Among the 373 patients in the study, we found
      statistically significant differences (p < .01) between the patients with normal
      renal function (CrCl > or = 60 ml/min, n = 300) and the patients with abnormal
      renal function (CrCl < 60 ml/min, n = 73) for the KAR, KVP, and KWP. The KAR was
      the parameter best correlated with CrCl and was an independent predictor of renal
      function from the patient's age, weight, and renal volume. Fifty-three patients
      with a KAR less than 1 had significantly worse renal function (CrCl = 60 +/- 21
      ml/min) than the patients with a KAR greater than or equal to 1 (CrCl = 95 +/- 31
      ml/min). Only 4% of patients with normal renal function had a KAR less than 1. A
      threshold value of KAR less than 1 had a sensitivity of 55%, a specificity of
      96%, a positive predictive value of 75%, and a negative predictive value of 90%
      for predicting renal dysfunction. CT parameters obtained at 30 sec were less
      useful than parameters at 90 sec. CONCLUSION: In patients undergoing clinically
      requested CT scanning, renal densitometry analysis can be used to depict patients
      with normal renal function; however, it has a high false-negative rate in
      depicting patients with diminished renal function.

PMID- 8883512
TI  - Density gradient of the lung parenchyma at computed tomographic scanning in
      patients with pulmonary hypertension and systemic sclerosis.
AB  - RATIONALE AND OBJECTIVES: Pulmonary hypertension may complicate systemic
      sclerosis in the absence of fibrosing alveolitis. Abnormal pulmonary perfusion is
      known to result in regional differences in lung density at computed tomographic
      (CT) scanning. We assessed possible disturbances in the normal CT density
      gradient in patients with systemic sclerosis and reduced gas transfer but no
      clinical or radiologic evidence of fibrosing alveolitis. METHODS: We analyzed the
      CT scans of 15 patients with systemic sclerosis. Regions of interest were drawn
      in the most dependent and nondependent zones in the upper and lower lobes of each
      lung. Average densities for the most dependent and nondependent zones were
      calculated for the upper and lower lobes, and a global lung density measurement
      was derived. Zonal and global density gradients were derived from mean density
      measures (mean density of dependent areas minus mean densities of nondependent
      areas). RESULTS: Five of the 15 patients had pulmonary hypertension, defined as
      an estimated systolic pressure in the pulmonary artery of greater than 30 mm Hg
      shown by Doppler echocardiography. Patients with pulmonary hypertension were
      characterized by higher global lung density for nondependent zones (median, -821
      H versus -853 H; p = .07) but not for dependent zones (-800 H versus -815 H, p =
      .71). The lung density gradient was reduced globally and in the lower zones in
      patients with pulmonary hypertension (p = .05). CONCLUSION: In cases of systemic
      sclerosis without fibrosing alveolitis, we found a significantly smaller density
      gradient between dependent and nondependent lung regions in patients with
      pulmonary hypertension compared with patients without pulmonary hypertension.
      This finding suggests that the normal CT density gradient depends in part on
      normal compliance of the pulmonary vasculature.

PMID- 8883513
TI  - Quantitative analysis of signal intensities and contrast after fat suppression in
      contrast-enhanced magnetic resonance imaging of the spine.
AB  - RATIONALE AND OBJECTIVES: We studied the effect of fat suppression on signal
      intensity and contrast on contrast-enhanced magnetic resonance (MR) images of the
      spine. METHODS: Contrast-enhanced T1-weighted MR images were obtained at
      identical levels with and without fat suppression. Signal intensity and contrast
      were measured in regions of interest in fat, muscle, spinal bone marrow, and
      enhancing lesions. The differences in the mean values of these signal intensities
      and the mean values of contrast between enhanced tissues and bone marrow, fat,
      and muscle were subjected to statistical validation. RESULTS: Mean signal
      intensity of the extraspinal fat and bone marrow was lower after fat suppression
      (70% and 46% reduction, p < .001 and p < .05, respectively), whereas the signal
      intensity of muscle showed no significant change (p < .9). Enhancing spinal
      lesions showed a difference in mean signal intensity after fat suppression (22%
      increase, p < .2). Contrast between enhanced lesions and bone marrow and fat was
      higher after fat suppression (78% increase, p < .01 for bone marrow; 8% increase,
      p < .001 for fat). CONCLUSION: In contrast-enhanced MR examinations of the spine,
      the use of fat suppression may increase the signal intensity of the enhancing
      lesion by expanding the dynamic gray scale of the image and increases the
      contrast between the lesion and adjacent bone marrow and suppressed fat.

PMID- 8883514
TI  - Detection of simulated lung nodules with computed radiography: effects of nodule
      size, local optical density, global object thickness, and exposure.
AB  - RATIONALE AND OBJECTIVES: We quantified differences in the detection of simulated
      lung nodules on computed radiographs on the basis of variations in nodule size,
      local contrast, body habitus (global contrast), and exposure. METHODS: A step
      wedge phantom was developed to simulate the attenuation ranges of the lung,
      retrocardiac, and subdiaphragmatic regions of the adult human chest. Additional
      Lucite wedges were used to simulate two different body thicknesses and to provide
      variable structural noise. Soft-tissue-equivalent nodules of 3-mm and 5-mm
      diameter that resulted in 10% differences in attenuation from lung equivalence
      were embedded in lung-equivalent material. By superimposing the sheets in various
      positions, 84 unique nodule configurations containing eight nodules per image
      were exposed on a computed radiography system. Computed radiographs were acquired
      at two different exposures approximating standard exposure and underexposure. For
      each resulting phantom image, seven observers scored the presence or absence of a
      nodule within individual cells of a 5 x 5 grid matrix. RESULTS: True-positive
      fractions for 3-mm-diameter nodules were very low across all conditions. True
      positive fractions for 5-mm-diameter nodules varied from 0.23 to 0.98.
      Significant differences in the conspicuity of 5-mm nodules depended on
      differences in phantom thickness and differences in the locations of nodules
      within lung-, retrocardiac-, or subdiaphragmatic-equivalent regions. Accuracy in
      detecting nodules was significantly lower at lower exposures when nodules were
      located in the subdiaphragmatic-equivalent region. CONCLUSION: On computed
      radiographs, small nodules (5-mm diameter) can be reliably detected when they are
      located in areas of high or moderate surrounding local contrast, such as the lung
      or mediastinal regions. Detection of nodules decreases in regions of lower
      optical density corresponding to the subdiaphragmatic regions of the chest. The
      decrease in nodule detectability is greatest under conditions that simulate large
      body thickness and underexposure.

PMID- 8883515
TI  - 1H-magnetic resonance spectroscopic observation of cultured malignant cells
      pharmacologically induced to different phenotypes.
AB  - RATIONALE AND OBJECTIVES: We evaluated the 1H nuclear magnetic resonance spectra
      of malignant cells after the administration of drugs that cause morphologic
      changes. METHODS: 1H spectra of a human lung adenocarcinoma cell line cultured
      with interferon gamma, dexamethasone, or sodium butyrate were obtained. The peaks
      were assigned by two-dimensional homonuclear Hartmann-Hahn spectroscopy spectra
      of the cells and their perchloric acid extracts. Differential spectra were used
      to evaluate relative changes in the peaks. RESULTS: In the control culture,
      choline/phosphocholine peaks were increased in the cell-growth phase, and the
      1.26-ppm peak was increased in the confluent state. Treatment by interferon gamma
      and dexamethasone induced reproducible changes in the peaks of differential
      spectra corresponding to 1.26 ppm, choline/phosphocholine, and
      glutamate/glutamine. Dexamethasone treatment broadened lipid peaks. Changes after
      treatment with sodium butyrate were obscure. Microscopically, cells were induced
      to morphologically different phenotypes by each drug. CONCLUSION: Cells induced
      to exhibit morphologically different phenotypes present different 1H spectra.

PMID- 8883516
TI  - Criteria for the assessment of intrinsic performances of digital radiographic
      intraoral sensors.
AB  - RATIONALE AND OBJECTIVES: In sensor-based dental digital radiographic imaging
      systems, it should be possible to assess the intrinsic performance of the sensor
      by means of objective criteria, independent of the related electronic hardware
      and image-treatment software. METHODS: Six criteria are presented and discussed
      for the objective assessment and quantification of the intrinsic performance of
      intraoral sensors for dental digital radiography, independent of the
      characteristics of the subsequent image-treatment software. The criteria are
      signal-to-noise ratio, blooming, sensitivity, spatial uniformity, modulation
      transfer function, and geometric deformations. These criteria have been used to
      evaluate the Visualix sensor. RESULTS: For each criterion, a series of numerical
      data are presented as graphs. CONCLUSION: A method is proposed for objective
      assessment of radiographic sensors that makes it possible to compare sensors with
      each other and with conventional radiographs. The criteria proposed also increase
      understanding of digital diagnostic images and improve their clinical use.

PMID- 8883517
TI  - The impact of ankle radiographs on the diagnosis and management of acute ankle
      injuries.
AB  - RATIONALE AND OBJECTIVES: We assessed the impact of ankle radiographs on
      referring physicians' diagnoses and treatment of acute ankle injuries. METHODS:
      Twenty emergency department physicians prospectively completed questionnaires
      before and after radiography on 101 patients with acute trauma receiving ankle
      radiographs. The questionnaires asked physicians to estimate the probability (0
      100%) of their most likely diagnosis before and after receiving the radiographic
      information. We also asked their anticipated and final treatment plans. We
      calculated the mean gain in diagnostic confidence percentage and the proportion
      of patients with changed initial diagnoses or anticipated management. RESULTS:
      The mean gain in diagnostic certainty from ankle radiographs was 34% (95%
      confidence interval [CI] = 28-40%). Ankle radiographs changed physicians' initial
      diagnoses in 37% (95% CI = 28-47%) of the patients. Immediate clinical management
      changed in 30% (95% CI = 22-40%) of the patients. CONCLUSION: Plain ankle
      radiographs have considerable impact on referring physicians' diagnoses and
      treatment of acute ankle trauma.

PMID- 8883518
TI  - Reducing the number of radiology residents: antitrust and action by the
      Accreditation Council for Graduate Medical Education.

PMID- 8883519
TI  - Meetings of the Association of American Medical Colleges and the Council of
      Academic Societies, 1995-1996.

PMID- 8883520
TI  - A cystic pancreatic mass in an elderly man.

PMID- 8883521
TI  - Contrast-medium-induced ventricular fibrillation: arrhythmogenic mechanisms and
      the role of antiarrhythmic drugs in dogs.

PMID- 8883522
TI  - Communicating with the patient: luxury or necessity?

PMID- 8883523
TI  - Iodixanol injection: a nonionic, isosmolar, hexa-iodinated contrast agent.
      Symposium proceedings.

PMID- 8883524
TI  - Safety, tolerance, and pharmacokinetics of iodixanol injection, a nonionic,
      isosmolar, hexa-iodinated contrast agent.
AB  - RATIONALE AND OBJECTIVES: A review of clinical-chemical parameters and
      tolerability of iodixanol is presented. Iodixanol is a newly developed dimeric,
      ratio 6 radiographic contrast medium formulated to be isotonic to plasma in all
      concentrations by the balanced addition of electrolytes. We summarize completed
      trials of iodixanol. RESULTS: The increase in femoral blood flow following
      administration of iodixanol was significantly smaller than that seen with most
      other nonionic contrast media. Iodixanol appears to have less impact than other
      nonionic media on renal tubular function. Unlike iohexol and ioxaglate, the rate
      of adverse events after iodixanol administration was essentially the same for
      normal patients as for patients at increased risk for negative reactions
      (patients with previous adverse reactions to contrast administration). The risk
      following administration of iodixanol also appears to be similar in normal
      patients and in patients with other risk factors, including those with a history
      of congestive heart failure, renal insufficiency or disease, asthma, diabetes,
      hypertension, or vascular disease. A significant reduction in the sensation of
      injection-associated heat and pain was noted for iodixanol versus ioxaglate.
      Cardiac electrophysiologic measurements and contractility revealed minimal
      interference from iodixanol. CONCLUSION: Iodixanol is a safe and effective
      nonionic, isotonic contrast medium that may offer clinical advantages.

PMID- 8883525
TI  - Variability of platelet degranulation by different contrast media.
AB  - RATIONALE AND OBJECTIVES: It has been suggested that nonionic but not ionic
      contrast media degranulate blood platelets when mixtures of blood and contrast
      media are studied by flow cytometry. This phenomenon was further assessed in the
      current study not only by performing whole-blood platelet flow cytometry but also
      by performing flowing blood platelet aggregometry. The latter is a highly
      sensitive measure of platelet function. METHODS: Blood samples were collected
      from six normal donors and mixed with equal volumes of an ionic monomer
      (diatrizoate), a nonionic monomer (iohexol), an ionic dimer (ioxaglate), and a
      nonionic dimer (iodixanol). Samples were collected in the presence of no
      anticoagulant for 1 min prior to the addition of sodium citrate or in the
      presence of heparin (14.5 U/ml) or recombinant hirudin (60 micrograms/ml). All
      samples were fixed in formaldehyde within 30 min. RESULTS: Platelet degranulation
      was observed with one nonionic agent (iohexol) and one ionic agent (diatrizoate).
      Degranulation was not seen with iodixanol or ioxaglate. CONCLUSION: These
      findings indicate that degranulation is independent of the ionic or nonionic
      nature per se of contrast media. A possible explanation for this conclusion is
      suggested.

PMID- 8883526
TI  - A randomized comparison of iodixanol and iohexol in adult intracranial computed
      tomography scanning.
AB  - RATIONALE AND OBJECTIVES: Nonionic iodinated contrast media have proved effective
      for computed tomography (CT) of the head and have demonstrated greater
      tolerability than their ionic counterparts. Iodixanol is a new nonionic agent
      with the added attribute of being isosmolar to blood and having less than half
      the osmolality of iohexol. Phase I safety, tolerance, and pharmacokinetic studies
      have indicated that iodixanol may be associated with fewer adverse effects than
      iohexol while providing equivalent diagnostic information. METHODS: We compared
      the safety and efficacy of iodixanol at 270 mg I/ ml (IOD-270) and at 320 mg I/ml
      (IOD-320) with iohexol 300 mg I/ml (IOH-300). RESULTS: No statistically
      significant differences in the quality of images or in the occurrence of adverse
      events were found among the three treatment groups. Pairwise comparisons of
      injection-associated discomfort revealed that significantly more patients in the
      IOH-300 group experienced discomfort than in either the IOD-270 or IOD-320
      groups. CONCLUSION: Iodixanol at 270 or 320 mg I/ml was found to be safe and
      effective when administered intravenously at a volume of 100 ml for intracranial
      CT scans in adult patients.

PMID- 8883527
TI  - Phase III clinical trial comparing iodixanol and iohexol in cerebral angiography.
AB  - RATIONALE AND OBJECTIVES: We report on our early clinical experience in the
      United States with the nonionic dimeric (6:1 ratio) contrast medium iodixanol in
      cerebral angiography. Iodixanol has an osmolality less than half that of
      monomeric, nonionic contrast media such as iohexol at equivalent iodine
      concentrations and is isosmotic to blood. METHODS: Forty-nine adult patients
      undergoing elective cerebral angiography were studied in a phase III, double
      blind, randomized, parallel-design clinical trial comparing the safety and
      diagnostic efficacy of iodixanol at 320 mg I/ml (IOD-320) and iohexol 300 mg I/ml
      (IOH-300). Diagnostically adequate cerebral angiograms were routinely obtained
      with both contrast agents. RESULTS: A total of 37% of the patients experienced
      adverse events (48% in the IOD-320 group and 25% in the IOH-300 group). No
      statistically significant differences were noted between the two groups studied
      in the proportion of patients with one or more adverse events or in the intensity
      of the adverse events. The most common adverse event was headache. There were no
      deaths or serious complications related to either contrast medium in this study.
      CONCLUSION: The results of this phase III trial support the conclusion that
      iodixanol at a concentration of 320 mg I/ml is comparable to iohexol at 300 mg
      I/ml in terms of efficacy (overall radiographic diagnostic visualization) and
      safety.

PMID- 8883528
TI  - A randomized comparison of iodixanol and iohexol in adult body computed
      tomography scanning.
AB  - RATIONALE AND OBJECTIVES: We compared the safety and imaging efficacy of
      iodixanol-270 (270 mg I/ml), iodixanol-320 (320 mg I/ml), both of which are
      isosmolal to blood, and iohexol-300 (300 mg I/ml) for body computed tomography
      (CT) scanning. METHODS: One hundred twenty-six patients from the University of
      Wisconsin Hospital and Temple University Hospital scheduled to undergo body CT
      examinations were randomly assigned to receive either iodixanol-270, iodixanol
      320, or iohexol-300. Patients were monitored with questioning and vital signs
      before injection, immediately after injection, and at 24 and 48 hr. Extensive
      laboratory evaluation also was performed. RESULTS: No serious reactions or deaths
      occurred in any group. The occurrence of overall minor adverse events (usually
      warmth, headache, taste distortion, rash) was similar for the different groups.
      Laboratory results showed no significant difference across groups. There was no
      significant difference in image quality detected among groups. CONCLUSION: There
      was no detectable difference in safety and imaging efficacy among the three
      contrast groups in this study. However, patients from the University of Wisconsin
      experienced significantly less injection discomfort with iodixanol-270 than with
      iohexol-300. Large clinical studies may more definitively determine the presence
      and nature of the relative advantages of iodixanol compared with currently
      available ionic and nonionic contrast agents.

PMID- 8883529
TI  - Comparison of iodixanol and ioxaglate for adult aortography and renal/visceral
      angiography: a phase III clinical trial.
AB  - RATIONALE AND OBJECTIVES: We investigated whether iodixanol offers improved
      safety or tolerance compared with ioxaglate and evaluated whether iodixanol
      enhanced radiographs are diagnostically comparable or superior to those produced
      with ioxaglate. Iodixanol is a new isosmotic hexa-iodinated nonionic contrast
      agent being evaluated for intravascular use. METHODS: Fifty-four adult patients
      undergoing renal or visceral angiography, aortography, or both were enrolled in a
      prospective, randomized, double-blind, two-center study in which iodixanol and
      ioxaglate were compared. Subjects were monitored for adverse events, injection
      associated discomfort, and changes in laboratory parameters and vital signs.
      Efficacy was measured by the overall quality of angiographic enhancement.
      RESULTS: No serious adverse events occurred during this trial. Mild-to-moderate
      adverse events were more common in patients receiving ioxaglate (p = .041).
      Injection-associated pain was reported by three patients receiving ioxaglate and
      none receiving iodixanol (p = .093). Clinical laboratory and vital-sign data
      showed no differences between groups, and there was no difference in the overall
      quality of angiographic visualization (p = .711). CONCLUSION: Iodixanol resulted
      in improved safety and patient tolerability while providing images of equivalent
      diagnostic efficacy compared with ioxaglate.

PMID- 8883530
TI  - Iodixanol and ioxaglate in adult aortography and peripheral arteriography: a
      phase III clinical trial.
AB  - RATIONALE AND OBJECTIVES: This study compared the safety and efficacy of
      iodixanol with those of ioxaglate in adult patients undergoing aortography or
      peripheral arteriography. METHODS: Forty-six patients were enrolled in this
      controlled, randomized, double-blind, two-center study. The patients were
      monitored for adverse events, injection-related discomfort, and trends in
      laboratory data or vital signs. Diagnostic efficacy was assessed by the quality
      of contrast enhancement. RESULTS: All procedures were diagnostic, with no
      significant difference in quality of visualization (p = .205). No significant
      difference was seen in the number of patients experiencing mild or moderate
      adverse effects (p = .106). Patients receiving ioxaglate reported a significantly
      greater incidence of injection-related pain (p = .025). CONCLUSION: The results
      of this study support the conclusion that iodixanol at 320 mg I/kg is safe and
      effective for adult aortography and peripheral arteriography and causes
      significantly less injection-related pain than ioxaglate.

PMID- 8883531
TI  - A prospective, parallel, double-blind comparison of iodixanol and iohexol in
      extremity phlebography.
AB  - RATIONALE AND OBJECTIVES: A two-center, prospective, double-blind study was
      conducted to compare the performance parameters (efficacy, safety, and injection
      associated discomfort) of iohexol with those of the new, isosmolar contrast
      medium iodixanol in extremity phlebography. METHODS: Ninety-nine patients from
      two centers, for whom venography was clinically indicated, were blindly
      randomized into two groups, iohexol at 300 mg I/ml (IOH 300) or iodixanol at 270
      mg I/ml (IOD-270). Patient vital signs and reports of adverse events were
      recorded for a minimum of 1 hr and monitored until the outcome was known. Any
      discomfort associated with the injection was also recorded. Laboratory measures
      included urinalysis, creatinine levels in serum and blood urea nitrogen. RESULTS:
      Both contrast media provided good or excellent visualization in nearly all
      patients (100% of patients in the IOD-270 group and 96% in the IOH-300 group).
      The incidence of adverse reactions was low in both groups (8.5% in the IOD-270
      group and 10% in the IOH-300 group). Injection associated discomfort lasting less
      than 4 min occurred in nine patients, four in the IOD-270 group and five in the
      IOH-300 group. Although clinically relevant changes in vital signs occurred in
      more than half the patients, most were judged to be anxiety related. Review of
      laboratory data revealed no evidence of toxicity for either agent. There was no
      statistically significant difference between the two agents with regard to any of
      these observed parameters. CONCLUSION: The data support the conclusion that both
      IOD-270 and IOH-300 are safe and effective agents when used for adult
      phlebography and are associated with little injection-site discomfort.

PMID- 8883532
TI  - Comparison of iodixanol with iohexol in excretory urography.
AB  - RATIONALE AND OBJECTIVES: We compared the safety and efficacy of iodixanol, a
      nonionic, dimeric, iodinated contrast agent, with that of iohexol, a monomeric
      agent, in adult excretory urography. METHODS: The study used a randomized, double
      blind, parallel-comparison design to evaluate image quality, vital signs,
      laboratory values, and adverse reactions. Seventy-five patients from each of two
      centers were included. One third received iodixanol at 270 mg I/ml, one third
      received iodixanol at 320 mg I/ml, and one third received iohexol at 300 mg I/ml.
      The dose for every patient was 1 ml/kg of body weight. The radiographs were
      interpreted and evaluated for quality by the primary investigator at each center.
      There were no important differences among the three groups in terms of
      demographics. RESULTS: Evaluation of each phase of the radiographic study showed
      almost uniform good-to-excellent opacification, with no significant differences
      among the three agents. No significant differences existed for the three groups
      in terms of vital signs, hematology, blood and urine chemistry, and injection
      discomfort. There were no deaths or serious reactions during the study, nor was
      there a statistically significant difference among the number of adverse events
      for the three agents. CONCLUSION: Iodixanol at both 270 and 320 mg I/ml proved to
      be a safe and effective contrast material for intravenous urography. In this
      study, its profile was essentially indistinguishable from that of iohexol at 300
      mg I/ml.

PMID- 8883533
TI  - Identification of a 283-kDa protein component of the particulate matrix
      associated with cardiac mesenchyme formation.
AB  - The elaboration of cardiac mesenchyme is controlled by a particulate form of
      extracellular matrix that is produced by the myocardium. This matrix consists of
      at least 7-10 major proteins or protein subunits. However, at present only a few
      of these proteins have been identified (i.e., ES130, fibronectin, transferrin).
      We report here the identification of a 283-kDa protein associated with this
      complex. This protein was identified using a new monoclonal antibody that is
      highly specific for this protein. The antibody does not react with human plasma
      fibronectin, chicken fibronectin or chicken cytotactin. In addition, this
      antibody inhibits the formation of mesenchyme when used in a bioassay of
      mesenchyme formation.

PMID- 8883534
TI  - Function of somite and somitocoele cells in the formation of the vertebral motion
      segment in avian embryos.
AB  - We have studied the distribution of thoracic somite and somitocoele-derived cells
      using homotopical grafting between quail and chicken embryos and reincubation
      periods of 2-6 days. Serial sections were evaluated with antibodies against quail
      cells, quail hemangiopoietic cells and desmin. With the exception of neural crest
      cells in the cranial sclerotome half, all cells of the operated segment are quail
      cells derived from a single somite. These cells differentiate into sclerotome,
      myotome and the anlage of the dermis of the back. After longer reincubation
      periods, the somite-derived quail cells form the neighboring halves of 2 adjacent
      vertebral bodies and the intervening (disc-homologous) tissue. Resegmentation is
      furthermore visible in the lamina and the spinous process. Somite cells also form
      the articular and transverse processes, and the intertransverse muscle including
      its insertion to the next cranial transverse process. One thoracic somite forms
      the proximal part of 1 rib. In more distal parts, 1 somite forms the cranial half
      of 1 rib and the caudal half of the next cranial rib, and the intercostal muscle
      and part of the connective tissue. Somite-derived quail cells are found in muscle
      that bridges over 2 segments cranial and caudal from the operated segment. The
      craniocaudal distribution of endothelial cells is approximately the same.
      Somitocoele cells that are located centrally in the epithelial somite express the
      sclerotome-markers Pax-1 and Pax-9. After 2-3 days of reincubation, grafted
      thoracic somitocoele cells are found mainly in the cranial part of the caudal
      sclerotome half. They form an area representing the anlagen of the intervertebral
      disc and the rib. After longer reincubation periods, the grafted quail
      somitocoele cells form the intervertebral disc-homologous tissue and the proximal
      part of the rib. In more distal parts of the rib they are located in the cranial
      half of 1 rib and the caudal half of the next cranial rib. The somitocoele cells
      also form the surface of the intervertebral joint, and give rise to a small
      number of endothelial cells that are found up to 1 segment cranial and caudal to
      the operation site. Our studies show that resegmentation is found in most parts
      of the vertebra and in the distal ribs. One somite forms the origin and insertion
      of the segmental muscle. Therefore, the somite can be regarded as the ancestor of
      the vertebral motion segment. Somitocoele cells are located centrally both in the
      epithelial somite and in the vertebral motion segment.

PMID- 8883535
TI  - Scanning electron microscopy of the basal surface of the epidermis of human
      digits.
AB  - The epidermal-dermal junction of the volar skin of human digits was examined by
      scanning electron microscopy (SEM). Fixed specimens obtained from cadavers were
      treated with 6 N NaOH to exfoliate the epithelium. The three-dimensional features
      of the basal surfaces were clearly visualized by SEM. Epithelial prolongations
      (intermediate and limiting ridges) protruded towards the dermis, and transverse
      ridges were visible between them. Nerve fibers and Schwann cells were aggregated
      around the sweat ducts on the intermediate ridges. Discoid structures were
      visible among the nerve fibers and Schwann cells. Examination by transmission
      electron microscopy of ultrathin sections of re-embedded specimens confirmed that
      the discoid structures were nerve endings that covered the Merkel cells. Minute
      projections were studded on the basal surfaces of basal keratinocytes. The
      projections in the intermediate ridges appeared to be villous, whereas the
      profiles of those in the limiting ridges resembled cobblestones. This
      morphological difference might be a reflection of function.

PMID- 8883536
TI  - Collagen fibril patterns in compact bone: preliminary ultrastructural
      observations.
AB  - A comparative study of the Haversian architecture was carried out on compact bone
      derived from the anterior and posterior edges of the diaphysis of horse radius,
      regions which have different mechanical requirements in vivo. Samples were heat
      deproteinated prior to SEM analysis, a treatment which effectively removes cells
      and vascular structures as well as exposing large areas of the mineralization
      front along the walls of the haversian canals. Bone subject to tensile stress
      revealed a prevalent alignment of its collagen fibrils in the stress direction,
      and the vast majority of its osteons were composed of fibrils running almost
      parallel and crossing at very acute angles. Bone subject to compressive forces
      showed either an orthogonal alternation of collagen lamellae or a
      multidirectional arrangement corresponding to the twisted plywood pattern
      described by other authors. Our observations substantiate both the classical
      model of the osteon and the twisted plywood concept, and suggest that osteon
      ultrastructure is modulated according to biomechanical requirements.

PMID- 8883537
TI  - Arrangement and identification of proteoglycans in basement membrane and
      intramuscular connective tissue of bovine semitendinosus muscle.
AB  - The arrangement and identification of PGs in the basement membrane and intra
      muscular connective tissues of bovine semitendinosus muscle were studied electron
      microscopically using cuprolinic blue, a cationic dye, to detect PGs. Three
      different types of PGs were observed in bovine semitendinosus muscle: The first,
      PGs of 20-40 nm in length, were arranged along the lamina lucida below the cell
      membrane. The second, PGs of 50-70 nm in length, were arranged randomly on the
      outer surface of the lamina densa. The third, PGs of 40-60 nm in length, were
      associated with collagen fibrils at regular intervals in the endomysium and
      perimysium. Cytochemical analysis using various GAG-degrading enzymes showed that
      PGs in the basement membrane were predominantly heparan sulfate PGs, and those
      associated with collagen fibrils in the perimysium were rich in chondroitin or
      dermatan sulfate, or both.

PMID- 8883538
TI  - Cardiac rod body: hypertrophic Z-line in an aged pony.
AB  - Numerous rod bodies were found in a heart sample from a 33-year-old pony by a
      conventional electron-microscopic technique. The rod bodies were concentrated in
      localized areas of both atria and ventricles, without a specific pattern of
      distribution. The rods appear to have a typical crystalline-like structure which
      presumably contains actin backbone filaments and alpha-actinin as major protein
      constituents. Diminution, fragmentation, and disorganization of the myofibrils,
      random expansion of electron-dense materials, especially at the fasciae adherens
      of the intercalated disc, an increase of intercellular space, frequently
      associated with connective tissue elements, and accumulation of glycogen
      granules, lipofuscin, mitochondria, and nonviable organelles in the rod body
      containing cells suggested that rod-containing myocytes are in a degenerating
      stage and that rod body formation occurs in atrophic cardiomyocytes rather than
      normal or hypertrophic cardiomyocytes in the aged pony heart.

PMID- 8883539
TI  - The lumbar anterior epidural cavity: the posterior longitudinal ligament, the
      anterior ligaments of the dura mater and the anterior internal vertebral venous
      plexus.
AB  - The contents of the anterior epidural cavity were studied to elucidate the
      relationship between veins, ligaments, and membranous formations. Anatomical,
      radiological and histological studies on human specimens after latex or
      gelatin/gadolinium venous injection at the level of the lumbar spine show that
      the posterior longitudinal ligament is a cross-shaped formation which includes
      the septum, the superficial part extending into the intervertebral foramen and
      the anterior ligaments of the dura mater. The anterior epidural cavity contains
      two medial and two lateral spaces. The two medial cavities enclose anterior and
      medial venous plexuses, which together receive the basivertebral veins; the two
      lateral cavities receive the anterior longitudinal veins. Contents of the medial
      and lateral cavities pass freely between the two. The lateral cavity connects
      with the intervertebral canal and dorsally into the posterior epidural space.

PMID- 8883540
TI  - Morphological modeling via isosurfacing: the laryngeal skeleton of gekkonid
      lizards as a test case.
AB  - A novel technique for modeling microscopic anatomical structures in three
      dimensions was developed as part of a survey of gekkonid laryngeal skeletal
      morphology (Reptilia: Gekkonidae). Excised larynges were transversely sectioned
      at 10 microns and stained using standard procedures. With a projection
      microscope, outline drawings of the sectioned laryngeal cartilages were made at
      regular intervals, depending on the rate and degree of structural change observed
      while sampling. The drawing set was digitized with a flatbed scanner, and aligned
      using 'NIH Image' for Macintosh computers. Physical connectivity between
      successive outlines was provided by inserting one or more artificial slices
      between those that had been digitized, and draping a skin of rendered contours
      over all of the interstitial spaces present in the template. The Application
      Visualization System, a general purpose visualization package for UNIX-based
      computer systems, was used to visualize and render the resulting 'isosurfaces',
      which appear as solid three-dimensional objects and can be viewed from any
      perspective. Since isosurfaced reconstructions can be based on as little as 20%
      of the cross-sections available, this procedure has the potential to be a
      valuable research tool for future morphological work at the microscopic level.

PMID- 8883541
TI  - Supernumerary tendons of the abductor pollicis.
AB  - During a study of variants of the tendon of the abductor pollicis longus (APL)
      muscle, in 1 of 110 upper extremities prepared, we recorded the rare finding of a
      division of the APL muscle tendon into 7 sections in the first tunnel. Whereas
      the actual main tendon inserted at the base of the first metacarpal bone, as
      depicted in the textbooks, the supernumerary tendons attached to the fascia of
      the opponens pollicis muscle to the radial edge of the abductor pollicis brevis
      muscle and to the dorsoradial third of the base of the first metacarpal bone. All
      accessory tendons were arranged in a radial formation around the main tendon
      within the same synovial sheath, but the main tendon occupied a separate
      compartment. In 80% of the upper extremities prepared for this study, the
      classical description of the abductor tendon did not apply. The classical
      representation of a single abductor tendon applied to only 20% of the upper
      extremities examined. In about one third of the wrists prepared, the first tunnel
      was clearly divided by a septum, so that 2 or more osteofibrous tunnels were
      present within the main tunnel. The number, thickness and length of such
      accessory tendons have a functional significance in the development of de
      Quervain's stenosing tendovaginitis and possibly also have a practical
      significance, as they may be regarded as a source of transplant material for
      plastic reconstructions.

PMID- 8883542
TI  - Uveal malignant melanoma. An ophthalmological or oncological disease?

PMID- 8883543
TI  - Posterior uveal melanoma. The Swedish perspective.
AB  - Posterior uveal melanoma is the most common primary intraocular malignant tumour
      and in Sweden some 70-80 new cases present each year. While uveal melanoma is
      more prevalent in the setting of ocular melanocytosis and neurofibromatosis,
      there is little conclusive data on the aetiology. Most patients experience a
      progressive visual field defect and present with a grey or greyish-brown mass of
      the posterior choroid. Diagnostic procedures include fluorescein angiography,
      ultrasound and magnetic resonance imaging. In some cases, intraocular biopsy may
      be required to make a correct diagnosis. Posterior uveal melanomas can usually be
      managed by any of a number of eye-preserving options like plaque radiotherapy and
      charged particle irradiation, but eyes containing large tumours are often
      enucleated. Nearly half of patients with posterior uveal melanoma, and in
      particular those with large tumours, ultimately succumb to metastatic disease.
      While most patients with tumour dissemination are treated with systemic
      chemotherapy possibly combined with interferon, metastatic spread confined to the
      liver may potentially be managed by intraarterial perfusion chemotherapy or liver
      resection. However, outcome of patients with systemic disease remains extremely
      poor with a median survival following detectable tumour dissemination of only two
      to five months. There are still insufficient data on the impact of various
      treatments on survival, but a large prospective trial addressing this issue is in
      progress. The present review summarizes the state-of-the-art knowledge and
      current management of posterior uveal melanoma from a Swedish perspective.

PMID- 8883544
TI  - Recurrence of malignant melanoma after irradiation diagnosed by glucose-fructose
      enhanced magnetic resonance imaging.
AB  - Two patients who had been given ruthenium plaque treatment for uveal melanoma
      were MR examined due to suspected recurrence. Spin-echo sequences were applied
      using a 1.5 T equipment. The examinations were performed in both patients two
      times with a 2-h interval. Immediately after the first examination the patients
      were perorally given 20 g glucose and 10 g fructose. An increase of signal
      intensity (prolongation of the relaxation times) and size of the uveal lesions
      could be visualized by a subtraction technique in both patients after the
      carbohydrate loading. In agreement with our previous studies of malignant
      melanoma the changed metabolism in the uveal lesions indicated recurrence of the
      tumour. One eye was available for histological examination. The morphological
      difference between areas of recurring and degenerating tumour was clearly seen.
      Similar changes were not observed by ultrasound.

PMID- 8883545
TI  - Conjunctival naevi in Denmark 1960-1980. A 21-year follow-up study.
AB  - The clinicopathological characteristics of 343 naevi of the conjunctiva were
      studied. A significant increase in the number of naevi excised per annum was
      observed. This may have been caused by an increased exposure to actinic rays.
      Approximately even distribution in the three main locations: caruncle, limbal
      area and eyeball, was found. Intrastromal naevi were excised at a higher median
      age than compound naevi, and the lowest observed median age at excision was for
      junction naevi, which is in accordance with the known histopathological nature of
      naevi. Recurrence occurred in nine patients (2.7%), and one transformed to a
      malignant melanoma. Eight of the recurring naevi were located in the limbal area.
      Eight of the nine patients were women, suggesting hormonal factors as a possible
      cause. Recommendations for the handling of conjunctival naevi are given, based on
      the present findings and on previous reports.

PMID- 8883546
TI  - Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and familial
      adenomatous polyposis (FAP).
AB  - Familial adenomatous polyposis (FAP) is a genetically transmitted disease
      affecting the colon. It is characterized by the presence of several (at least
      100) adenomatous polyps, each able to develop into carcinomas, and by other extra
      colonic signs such as skin and bone lesions. Within the framework of research
      studies to identify phenotyphic markers for early detection of subjects at risk
      within a family affected by FAP, attention has recently been paid to congenital
      hypertrophy of the retinal pigment ephitelium (CHRPE). With the aim of evaluating
      the relationship between FAP and CHRPE, 36 members of 7 FAP families were
      examined. We found that 43.75% of the subjects presenting CHRPE areas were also
      affected by FAP, whereas 58.33% of patients affected by FAP had CHRPE. Our
      findings indicated a lower incidence of CHRPE in FAP patients, compared to other
      studies reported so far. Moreover, in a control group of 160 healthy individuals
      we found a CHRPE prevalence of 5.5%.

PMID- 8883547
TI  - Biochemical studies on the secretion of glycoproteins by isolated ciliary body of
      rabbits.
AB  - The contribution of the ciliary body to the origin of vitreous proteins was
      investigated in rabbits by incubating explants of this eye component under novel
      conditions. At the end of incubations for up to 21 h, the tissues were processed
      histologically and were shown to be in an excellent state of morphological
      preservation. When radioactive amino acids and fucose were added to the culture
      medium, protein and glycoprotein synthesis and secretion were detected using
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) plus
      fluorography. The origin of these secretory products was traced by
      autoradiography to the ciliary epithelium. When samples of vitreous bodies -
      injected intravitreally with the same radioactive precursors - were run beside
      samples of the tissue culture media, comigration of at least 8 radioactively
      labelled bands including the one previously identified as transferrin was
      detected. This indicates that some vitreous proteins may be secreted by the
      ciliary body and that cultures of explants of ciliary body-iris are useful tools
      for studies on vitreous protein secretion.

PMID- 8883548
TI  - High precision Twyman-Green interferometer for the measurement of ophthalmic
      surfaces.
AB  - PURPOSE: We developed a method for measuring ophthalmic surfaces based on a
      Twyman-Green interferometer. METHODS: To demonstrate the accuracy, we measured
      the anterior surface of four used hard contact lenses and evaluated the
      interference pattern with phase shift technique. The obtained interferograms were
      evaluated by an image processing system. RESULTS: The interferometric resolution
      of the measurement is up to lambda/20 (30 nm) which refers to a dioptric
      resolution of about delta D = 10(-3) m(-1) for typical anterior radii of
      curvature. The dioptric maps were calculated from the height distribution. As we
      used a focus tracking distance measurement setup with an accuracy of 10 microns
      we could determine the absolute value of the dioptric number to be delta D
      approximately 0.04 m-1. To demonstrate the accuracy we tested contact lenses
      which were specified to have a spherical anterior surface. Obviously, the
      topography of contact lenses changes when worn. We measured astigmatic deviations
      up to 0.6 D in the central zone of the lenses. We briefly discuss the
      possibilities of this method concerning a topographer for measuring the fine
      corneal surface structure. CONCLUSIONS: The presented Twyman-Green interferometer
      with distance measurement and image processing system is a very accurate method
      for measuring the topographic properties of ophthalmic surfaces. The method may
      also be useful for studying the distribution of the tear layer on the contact
      lens, or the corneal topography.

PMID- 8883550
TI  - Tear film and meibomian gland functions in psoriasis.
AB  - Tear secretion, tear film stability, and meibomian gland function (plugging,
      volume, and thickness) were assessed in patients with psoriasis vulgaris (n =
      70). As compared to that of the healthy controls (n = 125) mean Schirmer I value
      of psoriatic patients was found to be in normal ranges, whereas tear film break
      up time was significantly lowered. When evaluating meibomian gland function,
      psoriatic patients were found to have higher plugging and thickness indices but a
      normal volume of meibomian gland secretion. These findings suggested an
      obstructive type of meibomian gland dysfunction in psoriatic patients which might
      result from increased turnover of the epithelia lining the meibomian gland duct.

PMID- 8883549
TI  - Isolation of functionally intact pig retina mitochondria.
AB  - Two alternative methods for the isolation of functionally intact mitochondria
      from pig retina were evaluated by means of differential centrifugation. If ATP
      and bovine serum albumin were present during the isolation procedures
      mitochondria exhibited ADP sensitive respiration and membrane potentials,
      comparable to values from other tissues. The mitochondria fraction of both
      methods differed in purity, being almost free of synaptosomes when a
      discontinuous Ficoll gradient centrifugation was used.

PMID- 8883552
TI  - Differences in optic discs in low-tension glaucoma patients with relatively low
      or high pressures.
AB  - We evaluated the differences in the optic nerve head in patients with chronic
      open-angle glaucoma (HTG) and those with low-tension glaucoma with either
      relatively high (between 16 and 21 mmHg [LTGH]) or low (< or = 15 mmHg [LTGL])
      intraocular pressures. We included 36 patients in this study. We found that LTGL
      patients had a significantly greater mean area of peripapillary atrophy inferior
      to the optic disc (0.65 +/- 0.38 mm2) than LTGH (0.40 +/- 0.38 mm2) or HTG (0.34
      +/- 0.25 mm2) patients (p < 0.005). No significant difference was found between
      groups for the area of the neural rim, optic disc, cup/pallor discrepancy, or
      peripapillary halo, or in the diameter of the largest artery or vein in the
      inferior and superior peripapillary area. This study raises the question of
      whether a separate mechanism of damage could exist at the optic disc in patients
      whose intraocular pressure is < or = 15 mmHg because of a greater extent of
      peripapillary atrophy than in patients with higher intraocular pressures.

PMID- 8883551
TI  - Regeneration of rat corneal epithelium is delayed by the inhibitory epidermal
      pentapeptide (EPP).
AB  - The effect of the inhibitory epidermal pentapeptide (EPP) on regeneration of rat
      corneal epithelium was studied over a 24-h period after removal of the central
      part of the corneal epithelium by means of n-heptanol and scraping. Both
      unphosphorylated and phosphorylated EPP inhibited the mitotic rate and the
      formation of new cells to the same extent. Thus, the mitosis inhibitor that
      originally was isolated from mouse epidermis, acts even on the ectodermally
      derived corneal epithelial cells.

PMID- 8883553
TI  - Glaucoma and visual outcome in central retinal vein occlusion.
AB  - Glaucoma is a recognized risk factor for central retinal vein occlusion. The
      authors retrospectively reviewed charts of fifty patients with central vein
      occlusion examined over a 5-year period. The visual outcome and clinical
      characteristics of eyes with and without glaucoma were compared. There were 32
      eyes without glaucoma and 18 eyes with glaucoma. Final visual acuity of 20/100 or
      better was obtained in 22% of eyes with glaucoma, compared with 34% of eyes
      without glaucoma, and final visual acuity of finger counting and less was found
      in 56% and 22%, respectively (p = 0.02). The rate of ischemic occlusion was
      higher in the glaucoma group, 44% and 28% respectively, but the difference did
      not reach statistical significance. There was no difference in the rate of
      neovascular complications and macular edema between the two groups. The results
      suggest that glaucoma has an adverse effect on the visual outcome of eyes with
      central vein occlusion.

PMID- 8883555
TI  - Contrast sensitivity in different types of early lens opacities.
AB  - The purpose of the present study was to evaluate the relationship of various
      types of early lens opacities with contrast sensitivity at different spatial
      frequencies. The Lens Opacities Classification System II and Lensmeter 701 were
      used in the grading of the lens status. The contrast sensitivity was tested with
      the Vistech VCTS 6500 distance test with optimal correction of refractive errors.
      Data from 995 eyes were available for the present study. Contrast sensitivity
      decreased by increasing lens opacification graded with the Lens Opacities
      Classification System II and also by increasing Lensmeter 701 reading. When the
      statistical model was adjusted for age and best corrected visual acuity, nuclear
      opacities and nuclear colour were not associated with decreased contrast
      sensitivity, however, there was a weak, but statistically significant correlation
      between contrast sensitivity reduction and cortical opacities at high spatial
      frequencies, and between contrast sensitivity and posterior subcapsular opacities
      at low and medium spatial frequencies.

PMID- 8883554
TI  - Modelling cortical cataractogenesis. XVIII. In vitro diabetic cataract reduction
      by venoruton. A flavonoid which prevents lens opacification.
AB  - The effect of a novel flavonoid, venoruton (a mixture of mono-, di-, tri- and
      tetrahydroxyethylrutosides) has been investigated in healthy rat lenses and
      compared with diabetic cataract modelled in vitro. One mM venoruton was added to
      medium simulating healthy and diabetic conditions for the incubated lenses;
      damage was followed by either stereoscopic photography of the lenses under a
      Cooperative Cataract Research Group operating microscope or with our recently
      developed method: the leakage of lactate dehydrogenase (LDH) into the lens
      culture media. The increased LDH activity in the medium and observable
      development of the opacity were correlated with cell damage, which has been found
      to be associated with globular degeneration and cataract formation. The extent of
      opacification and LDH release is reduced if 1 mM venoruton is included in the
      medium. The protective effect may be related to antioxidant activity against
      reactive oxygen species: decreased luminol luminescence was shown after venoruton
      addition to either superoxide-generating hypoxanthine plus xanthine oxidase, or
      hydrogen peroxide.

PMID- 8883556
TI  - Glycoprotein deposition in vascular walls of diabetic retinopathy. A
      histopathological and immunohistochemical study.
AB  - The association between periodic acid Schiff staining and immunoreactivity to
      laminin, fibronectin, vitronectin, and type VI collagen was studied qualitatively
      and quantitatively in the retinal vascular bed from 7 eyes of 5 diabetic patients
      and from 5 eyes of 5 normal persons. In the retina from diabetic patients the
      number of arterioles showing immunoreactivity to vitronectin, the number of
      venules showing immunoreactivity to type VI collagen, and the number of both
      arterioles and venules showing immunoreactivity to laminin and fibronectin, was
      higher than in normals. There was no difference between the number of capillaries
      showing periodic acid Schiff staining and immunoreactivity to laminin,
      fibronectin, and vitronectin when comparing areas of vascular occlusion with
      adjacent control areas. However, the number of capillaries displaying
      immunoreactivity to type VI collagen was higher in control areas than in areas of
      vascular occlusion in diabetic patients and in normal controls. Staining with
      periodic acid Schiff correlated topographically with immunoreactivity to laminin
      and fibronectin, but not with immunoreactivity to vitronectin and type VI
      collagen. In areas of vascular occlusion there was seen no immunoreactivity or
      histological staining corresponding to the material accumulated to occlude the
      ghost vessels.

PMID- 8883557
TI  - Topical urea as a treatment for non-infectious keratopathy.
AB  - The purpose of this study was to evaluate topical urea ophthalmic ointment as an
      agent to promote epithelial healing. Corneal epitheliopathy and epithelial
      defects were chemically induced in rabbits. Urea ophthalmic ointment was
      administered to one eye and control ointment to the fellow eye. The rabbits were
      examined by a masked observer for eleven days and points were awarded for steps
      of improvement in their ocular surface disease. The eyes receiving the urea
      ointment improved an average of 5.73 points while the control eyes improved 4.2
      points (p < 0.0001). In conclusion, topical urea dissolved in a bland ointment
      encourages corneal reepithelialization and limits epithelial damage after toxic
      injury to corneal epithelium.

PMID- 8883558
TI  - Current trends in newly registered blindness in Denmark.
AB  - Current pattern of blindness (i.e. visual acuity < or = 6/60) in Denmark was
      studied based on 1585 application forms for new membership to the Danish Society
      of the Blind during 1993. Statistics on blindness are very sensitive to the
      definitions used. A change of blindness definition to visual acuity < 6/60
      reduced the number of formally blind subjects with 32%, and by using the
      definition of WHO (visual acuity < 3/60) only 562 subjects (35%) would have been
      considered blind. The prevailing causes of blindness were age-related macular
      degeneration with 1132 cases (71.4%), followed by diabetic retinopathy 133 cases
      (8.4%), and glaucoma 80 cases (5.0%). Among the younger subjects (133 persons)
      aged 20-59 years diabetic retinopathy comprised 36% and lesions of the optic
      pathways 26%, while myopia and retinitis pigmentosa accounted for 5% each. The
      majority of the applicants (92%) were > or = 60 years old. In this group, age
      related macular degeneration was the main cause of blindness in 78%. Figures from
      1993 were compared with six similar studies on newly registered blindness from
      the last 35 years. The annual number of registrations was doubled during the last
      25 years. The annual number of registered blind due to diabetic retinopathy fell
      during the 60's and 70's followed by a constant rate during the last decades.
      Glaucoma blindness fell with a factor two, and declined from a relative frequency
      of 15% among the causes of blindness to 5%. The impact of age related macular
      degeneration increased from 20% to 70% during the same period.

PMID- 8883559
TI  - The incidence of registered blindness caused by age-related macular degeneration.
AB  - Membership applications to the Danish Society of the Blind were used as a
      register source of legal blindness (visual acuity < or = 6/60). Based on
      application forms completed by specialists in ophthalmology 1585 subjects were
      recorded as blind in 1993. 1132 subjects (71.4%) had age-related macular
      degeneration. Only 5% of the registered subjects with age-related macular
      degeneration were below 70 years of age. The median age was 82, equal for both
      gender. A female overrepresentation of 2.8:1 was found. Five-year age-specific
      incidence rates demonstrated an exponential rise of registered blindness due to
      age-related macular degeneration from age 60 to 90. A decline in incidence after
      the age of 90 is assumed to reflect underregistration of very old persons. This
      tendency of non-registration was particularly pronounced in elderly males.
      Estimated prevalence rates of registered blindness due to age-related macular
      degeneration increased 100-fold from the age group 60-64 to the age group 80-84.
      The age specific incidence rate for the age group 60-99 years was 140:100,000 for
      females and only 66:100,000 for males. The corresponding incidence rate for both
      sexes was 108:100,000. It is still a matter of dispute whether 'true' prevalence
      rates of blindness are higher in females than in males. The sex difference seems
      not to be explained by differences in 'visual impairment threshold of
      registration' among the registered persons.

PMID- 8883560
TI  - A descriptive study on Behcet's disease.
AB  - This study was performed in order to evaluate the age, sex, geographical
      distribution, ocular involvement, age of onset, and attacks in Behcet's disease.
      We examined 540 Behcet patients between 1973-1993. Of the patients, 453 were male
      and 87 female (m/f: 5.2/1). The average age was 30.7 +/- 0.35. The disease mostly
      appeared in the third decade and it was statistically significant that sex
      affected the age at onset of the initial symptoms. The onset of symptoms was more
      frequent among males in the 25-29-year age group, and among females below 19 and
      above 35 years of age. The duration of the disease was 28.7 +/- 3.1 months. The
      state of ocular attacks were evaluated in 598 eyes of 303 patients who were
      followed regularly during the first year. The risk and frequency of attacks were
      greater in the eyes with poorer visual acuity, and in such eyes, the number of
      attacks was greater < or = 24 while smaller > or = 35 years of age.

PMID- 8883561
TI  - The spectrum of herpes simplex virus disease of the anterior segment in the
      1990s.
AB  - We have sampled our clinic population in order to ascertain the proportion with
      herpetic eye disease of the anterior segment. The age, gender predominance, and
      incidence of bilateral disease amongst such patients has not changed over the
      past 20 years. The predominant disease type was stromal keratitis, with
      significant morbidity and visual handicap. Herpetic eye disease of the anterior
      segment utilizes only 1% of out-patient clinic resources overall, but 17% of
      specialist external disease clinic time. There was a statistically significant
      correlation between total length of follow-up and reduced visual acuity. It would
      seem that the prevalence of herpetic eye disease of the anterior segment appears
      to have halved since comparable reports were published. In addition, the
      prognosis of the disease, in terms of the prevalence of visual impairment, has
      worsened.

PMID- 8883563
TI  - Histopathological and lectin histochemical study of exfoliation syndrome.

PMID- 8883562
TI  - The effects of nasolacrimal canal blockage on topical medications for glaucoma.
AB  - Twenty patients with primary open angle glaucoma who have been treated with
      identical antiglaucoma eye drops in both eyes were examined. Silicone punctal
      plugs were used to occlude the inferior punctum of one eye, in order to block the
      nasolacrimal canal. The intraocular pressures and effects of the medical therapy
      before and after punctal occlusion were compared. Punctal occlusion significantly
      decreased the intraocular pressure with an average of 2.00 +/- 0.43 mmHg in the
      plugged eyes (p < 0.001). The intraocular pressure in the unplugged control eyes
      did not change significantly (p > 0.05) after punctal occlusion of the fellow
      treated eye.

PMID- 8883564
TI  - Posterior segment visualization problems with multifocal intraocular lenses.

PMID- 8883565
TI  - Bilateral simultaneous surgery.

PMID- 8883566
TI  - The Kleinian Psychoanalytic Diagnostic Scale (revised version): presentation and
      study of reliability.
AB  - The Kleinian Psychoanalytic Diagnostic Scale (KPDS) is a psychodiagnostic
      instrument of assessment based on the psychoanalytical theory of object
      relations. It was created in order to introduce an intrapsychic and relational
      dimension into the clinical research on and epidemiology of psychiatric
      diagnosis. It consists of 15 subscales grouped into the following four
      dimensions: "Ego Abilities'; "Projective Identification'; "Paranoid-Schizoid';
      and "Depressive'. These dimensions constitute different, relatively stable
      aspects of the mental life of the subject, their demarcation and description
      permitting the obtention of a chart and profile of the intrapsychic and
      relational structure. Following several free, unstructured interviews the scale
      is assessed on the basis of what the subject says and what the rater may detect
      in the relationship. The inter-rater reliability of the scale, its stability over
      a time lapse, as well as its internal consistency have all been shown to be high.

PMID- 8883568
TI  - Contrasts in neuropsychological test profile between patients with first-episode
      schizophrenia and first-episode affective disorders.
AB  - Patients with first-episode (FE) schizophrenia (n = 27), unipolar depression (n =
      10) and bipolar disorder (n = 17) and age- and gender-matched healthy control
      subjects (n = 27) were administered a battery of neuropsychological (NP) tests.
      FE schizophrenics performed significantly less well than patients with affective
      disorders in the area of visual motor processing and attention. Affective
      disorder patients without psychotic features did not perform significantly
      differently to controls. However, affective disorder patients with psychotic
      features performed as poorly as schizophrenics, with the most pronounced
      impairment in the area of visual motor processing and attention. Our data
      tentatively suggest the existence of a dichotomy in neuropsychological
      impairment, with psychotic patients showing similar neuropsychological deficits,
      while non-psychotic affective patients perform comparably to controls.

PMID- 8883569
TI  - Are suicide rates in Sweden associated with changes in the prescribing of
      medicines?
AB  - A key issue in the debate on suicide prevention is the extent to which suicide
      rates are affected by the availability of means of committing suicide. The aim of
      this study was to analyse the changes in rates of suicides committed by poisoning
      in Sweden between 1969 and 1992, and to determine to what extent these were
      associated with changes in the prescribing of medicines. We compared suicide
      rates from 1969 to 1992 with trends in the sales of antidepressants,
      barbiturates, neuroleptics and analgesics during the same period. The incidence
      of suicide by poisoning decreased during the 1970s, especially in younger and
      middle-aged men. This was mainly due to a decrease in suicides by barbiturate
      poisoning, which closely followed a decrease in sales of barbiturates. Sales of
      analgesics and antidepressants increased during the study period, and so did the
      rates of suicide using these drugs. We conclude that the availability of
      medicines is an important factor influencing suicide rates, and that changes in
      the prescribing of medicines may influence suicide rates.

PMID- 8883567
TI  - Is there a suicidality syndrome independent of specific major psychiatric
      disorder? Results of a split half multiple regression analysis.
AB  - Biological findings such as low 5-HIAA levels in cerebrospinal fluid (CSF) in
      suicidal patients compared to non-suicidal patients independent of the type of
      psychiatric disorder indicate a broad basis for suicidality. It is therefore
      important to ask whether a suicidality syndrome can be delineated on a
      phenomenological level, and whether it is independent of specific major
      psychiatric disorders which are otherwise considered to be aetiologically
      different. This paper reports on a study of 2383 schizophrenic and 1920
      depressive unselected patients with and without suicidality. They were assessed
      during the first 24 h after admission to a psychiatric in-patient facility using
      a comprehensive psychopathological assessment (AMDP system). Using multiple
      variance analysis and logistic regression analysis based on single symptoms, for
      both suicidal and non-suicidal patients it was shown that a suicidality syndrome
      independent of the underlying illness can be delineated. In schizophrenia as well
      as in major affective disorders it was found that hopelessness, ruminative
      thinking, social withdrawal and lack of activity are core symptoms of this
      suicidal syndrome. The finding of a suicidality syndrome, not associated with a
      specific major affective disorder, indicates the need to identify this syndrome,
      which should be seen as an independent dimension and diagnosed separately, and
      not regarded merely as a secondary symptom of major psychiatric disorders,
      particularly affective disorders.

PMID- 8883570
TI  - Decreased efficacy of combined benzodiazepines and unilateral ECT in treatment of
      depression.
AB  - In a retrospective study, 124 patients with depression who were concomitantly
      receiving ECT and benzodiazepines were compared with patients (matched for age,
      sex, diagnosis, and laterality of ECT) receiving ECT without benzodiazepines in
      order to investigate the efficacy of ECT in terms of therapeutic response and
      length of stay in hospital. Most of the subjects (84% of cases and 89% of
      controls) improved on ECT, but the benzodiazepine group of patients receiving
      unilateral ECT showed a significantly poorer response and a longer stay in
      hospital. No such difference was detected with the bilateral ECT. It is therefore
      concluded that prescription of benzodiazepines with ECT does compromise the
      therapeutic effect of unilateral ECT for depression.

PMID- 8883571
TI  - Psychopathy, platelet MAO activity and criminality among former juvenile
      delinquents.
AB  - Psychopathy-related personality traits as well as platelet monoamine oxidase
      (MAO) activity and criminality from the age of 15 years were studied in a group
      of 68 male former juvenile delinquents and 32 control subjects. The former
      juvenile delinquents registered for crime as adults were found to have higher
      Psychopathy Check List (PCL) scores and lower platelet MAO activity than either
      juvenile delinquents who were not registered criminals from the age of 15 years
      or non-criminal controls. Although PCL scores and platelet MAC activity were
      unrelated, a configural frequency analysis showed a significant interaction.
      Individuals with PCL scores, low platelet MAO activity and persistent criminal
      behaviour constituted a significant "type'. Among the 27 former juvenile
      delinquents who developed persistent criminality, 21 subjects (78%) had PCL
      scores greater than 0 and low platelet MAO activity, while none of these
      persistent criminals were characterized by a combination of zero PCL score and
      high platelet MAO activity.

PMID- 8883572
TI  - Criminality and psychopathy as related to thyroid activity in former juvenile
      delinquents.
AB  - Levels of triiodothyronine (T3) and thyroid-stimulating hormone (TSH),
      psychopathy-related personality traits and criminality from the age of 15 years
      onward were examined in 70 former juvenile delinquents and 35 control subjects
      aged 38-46 years. T3 levels were significantly associated with criminality but
      not with psychopathy-related personality traits. TSH levels were not related to
      any of these variables. Juvenile delinquents who displayed persistent criminal
      behaviour were found to have higher mean T3 levels than juvenile delinquents who
      did not display criminality in adulthood and non-criminal controls. Former
      juvenile delinquents with T3 levels above the mean level found in the controls
      were registered for criminality 3.8 times more often than juvenile delinquents
      with T3 levels below the mean level found in the control group. The results are
      discussed in terms of elevated T3 levels representing a compensatory or stress
      phenomenon for low social adaptive ability of individuals who display persistent
      criminal behaviour.

PMID- 8883573
TI  - Quality of life in schizophrenia: relationship to sociodemographic factors,
      symptomatology and tardive dyskinesia.
AB  - The influence of sociodemographic, clinical and treatment factors on the quality
      of life of patients with schizophrenia has yet to be fully defined. We evaluated
      the quality of life of patients with schizophrenia who were attending a catchment
      area rehabilitation centre, in order to establish its clinical correlates. These
      patients had a poor to moderate quality of life which was inversely related to
      negative symptom severity, illness duration, the cumulative length of previous
      hospitalization and patient age. Patients residing in hostels or group homes had
      a poorer quality of life than those living independently or with their family.
      The presence of tardive dyskinesia was associated with a poorer quality of life.
      This association merits further investigation.

PMID- 8883574
TI  - Living conditions of female suicide attempters: a case-control study.
AB  - A total of 51 hospitalized female suicide attempters (17-64 years old) were
      interviewed according to a questionnaire used by Statistics Sweden, SCB (ULF
      88:1) for investigation of living conditions. Control subjects from similar
      geographical areas included in the ULF investigation in 1988, and matched for age
      and nationality, were identified through the SCB (n = 153). Odds ratios (OR) and
      95% confidence limits were estimated. Correlation coefficients were used to study
      the relative importance of specific factors. Not less than 26 items reached the
      level of statistical significance, but only four of them (mental disorder, use of
      anxiolytics, unemployment at some time during the last 5 years, and no
      professional work during the past year) showed a considerable excess risk (lower
      95% CI limit for OR > 3). Physical illness was relevant as an independent factor.
      Although of secondary importance, hospitalization during the previous 3 months
      was also a characteristic of suicide attempters.

PMID- 8883575
TI  - General practitioners' views of an open referral system to a community mental
      health service.
AB  - The satisfaction of general practitioners with a community mental health service
      operating an open referral system was compared to that with two services both
      operating a closed referral system covering the same inner-city district. The
      open referral system allows any agency (including patients) to contact the
      service by letter or by telephone, and priority is given to patients with serious
      mental illness. General practitioners' satisfaction with all aspects of the open
      referral system was greater than that with either of the closed referral systems.
      In particular, speed of assessment of referrals was preferred in the open
      referral system.

PMID- 8883576
TI  - Marked symptom reduction in two women with bulimia nervosa treated with the
      testosterone receptor antagonist flutamide.
AB  - Previous reports indicate that elevated serum levels of androgens in women may
      contribute to the development of bulimia nervosa and other conditions
      characterized by impaired impulse control and/or depressed mood. This report
      describes the effect of treatment with the testosterone antagonist flutamide (250
      500 mg daily) in two women with severe bulimia. Both subjects reported a marked
      improvement with respect to bulimic behaviour within a week after initiation of
      flutamide treatment; when the drug was withdrawn, both patients relapsed. It is
      concluded that further investigations of the possible efficacy of androgen
      antagonism in eating disorders are warranted.

PMID- 8883577
TI  - Quantitative HIV-1 RNA as a marker of clinical stability and survival in a cohort
      of 302 patients with a mean CD4 cell count of 300 x 10(6)/l.
AB  - OBJECTIVE: To analyse plasma HIV-1 RNA levels as a marker of clinical stability
      and survival in a cohort of HIV-infected patients whose time of seroconversion is
      unknown. DESIGN: Retrospective cohort study. SETTING: Retrovirology laboratory
      and AIDS Unit in a teaching hospital. PATIENTS: A total of 916 samples from 302
      patients, most on antiretroviral therapy, were analysed. Mean initial CD4 cell
      counts and HIV-1 RNA were 299 x 10(6)/l (range: 0-1600) and 134,261 copies/ml
      (range: < 200-4,300,000), respectively. Sixty-six cases had been diagnosed
      previously with AIDS. METHODS: Analysis of progression to AIDS and survival,
      according to initial and longitudinal viral load (VL) and CD4 cell count
      measurements was performed by Kaplan-Meier test. Relative risks were calculated
      by Cox's proportional hazards model. RESULTS: During a mean follow-up of 444 +/-
      309 days, 29 patients developed AIDS and 21 died. Relative risk (RR) of
      progression related to the group with VL < 35,000 was: 10.4 when CD4 > or = 250 x
      10(6)/l and VL > or = 35,000 (P = 0.001); and 45.3 when CD4 < 250 x 10(6)/l and
      VL > or = 35,000 (P < 0.0001). Cumulative probability of progression was: 0%, 0%
      and 12.3%, at the first, second and third year respectively, for patients with
      all their sequential VL determinations < 60,000; and 13.3%, 34.7% and 79.3% for
      patients who did not maintain VL values always < 60,000 (RR = 23; P < 0.0001).
      The minimum value of VL that reached statistical significance for the survival
      analysis was 100,000 copies/ml (P < 0.0001). CONCLUSIONS: VL > or = or < 35,000
      is a better discriminant for progression than a CD4 cell count > or = or < 250 x
      10(6)/l. Sequential VL determinations < 60,000 are associated with a better
      prognosis.

PMID- 8883578
TI  - Virus inactivation in blood.

PMID- 8883579
TI  - HIV infection in vitro enhances the activity of src-family protein tyrosine
      kinases.
AB  - OBJECTIVE: We examined the effect of HIV infection on src-family protein tyrosine
      kinase (PTK) activity to determine if alterations in src-family PTK activity
      could contribute to the HIV-related chronic immune system activation observed in
      patients infected with HIV. METHODS: Jurkat, a CD4+ human T lymphocyte cell line
      was infected with HIV IIIB. Kinase activity was determined by in vitro immune
      complex kinase assays using antibodies specific for the src-family PTKs, p56lck,
      p59fyn and p60c-src expressed in T lymphocytes. PTK protein and total
      phosphotyrosine levels were assessed by Western blotting. The role of the gp120
      CD4-Lck interaction in HIV-related PTK activation was determined using gp 120
      treated Jurkat cells and HIV-infection of JCaM 1.6 cells, a Jurkat-derived cell
      line that lacks p56lck. RESULTS: Cells infected with HIV for 24 h exhibited
      increased levels of total tyrosine phosphorylation and enhanced src-family PTK
      activity without altered levels of expression of src-family kinases. The activity
      of Lck and Fyn was enhanced within 30 min of infection. HIV-related src-family
      PTK activation was not a function of the gp120-CD4-Lck interaction and occurred
      in the presence of 10 mmol/l zidovudine indicating that reverse transcriptase and
      activation of the HIV genome is not required. CONCLUSIONS: HIV-related activation
      of src-family PTK is a response of the cell to early stages of the virus life
      cycle, possibly either membrane fusion or viral uncoating. These results indicate
      that endogenous src-family PTKs may play a role in HIV-related immune activation
      and dysfunction. Moreover, activation of src-family PTK may be a mechanism used
      by the virus to facilitate some aspect of its own life cycle.

PMID- 8883581
TI  - Selection conditions affect the evolution of specific mutations in the reverse
      transcriptase gene associated with resistance to DMP 266.
AB  - OBJECTIVE: To monitor the appearance of HIV-1 variants resistant to inhibition by
      DMP 266, a benzoxazinone non-nucleoside reverse transcriptase inhibitor using two
      different protocols for applying drug selective pressure in tissue culture. To
      compare the phenotype and genotype of viral isolates selected by each method.
      METHODS: MT-2 cells and fresh donor peripheral blood mononuclear cells (PBMC)
      were infected with HIV-1 strain RF. The MT-2 cells were infected in the presence
      of a 50% inhibitory concentration (IC50) of DMP 266 and the concentration was
      slowly increased during the selection period. The PBMC were infected for 1 week
      in the absence of inhibitor and then a single concentration was maintained
      throughout the selection period. Both cultures were passaged for approximately 4
      months. Virus and cell pellets were harvested over this in vitro selection
      period, the RT genes amplified by polymerase chain reaction from the cell
      pellets, and the proviral DNAs sequenced. Isolated virus was tested for DMP 266
      susceptibility in either the AIDS Clinical Trials Group/Department of Defense
      consensus assay or MT-2 yield reduction assay. RESULTS: Passage in MT-2 cells
      resulted in accumulation of three substitutions in RT (V179D, L1001, Y181C) after
      24 passages associated with 1000-fold reduced susceptibility to DMP 266. In PBMC
      cultures treated with 0.96 microM DMP 266, virus replication was completely
      suppressed after 2 weeks; no regrowth occurred in the presence of compound after
      10 weeks or in the absence of compound for 3 additional weeks. The 0.096 microM
      treated cultures had an initial 2.5-log reduction in infectious virus titre
      followed by rapid regrowth. Virus obtained at week 6 displayed a 28-fold
      reduction in susceptibility with an L1001 substitution in RT, and by week 11
      displayed a 1000-fold reduction in susceptibility with an additional V1081
      substitution. CONCLUSIONS: High-level resistance to DMP 266 may develop by at
      least two pathways and experimental conditions influence the genotype selected.
      The continued absence of detectable virus in the PBMC cultures grown at 0.96
      microM is supportive evidence that maintaining trough plasma levels of DMP 266
      which result in sustained antiviral activity in vivo may delay emergence of
      highly resistant viral variants. Confirmation of this hypothesis will require
      clinical trials.

PMID- 8883580
TI  - Antibody-dependent cellular cytotoxicity to clinical isolates of HIV-1 and
      SIVcpz: comparison of human and chimpanzees.
AB  - OBJECTIVE: To investigate differences in the antibody-dependent cellular
      cytotoxicity (ADCC) responses between HIV-1-infected humans and chimpanzees.
      DESIGN: The breadth of the ADCC responses in the two populations were tested
      against autologous and heterologous HIV-1 and SIVcpz clinical isolates as well as
      against reference isolates. METHODS: ADCC was tested in a 51Cr-release assay
      using human peripheral blood mononuclear cells as effector cells and infected
      Jurkat/Tat-cells as target cells. RESULTS: The majority of sera from chronically
      HIV-1-infected humans and chimpanzees had ADCC responses to HIV-1LAI.
      Interestingly, vaccinated chimpanzees with a low virus load during the immediate
      post-challenge period had low ADCC responses 3 years after challenge. In
      contrast, when ADCC activity to clinical isolates was evaluated, HIV-1-infected
      chimpanzees had more frequent heterologous (broader) responses than HIV-1
      infected humans. ADCC was also tested in consecutive serum samples from two
      patients and two chimpanzees against autologous isolates, but was only detected
      to a low degree in one of the animals, although heterologous ADCC was
      demonstrated in all cases. The naturally infected (SIVcpz) chimpanzee did not
      have detectable heterologous or autologous ADCC responses. CONCLUSIONS: HIV-1
      infected chimpanzees had broader ADCC reactivity to heterologous HIV-1 clinical
      isolates than the HIV-1-infected humans. These findings are consistent with
      subtle differences in host-virus relationships of these two species.

PMID- 8883582
TI  - Spindle cells isolated from Kaposi's sarcoma-like lesions of BKV/tat-transgenic
      mice co-express markers of different cell types.
AB  - OBJECTIVE: To characterize murine spindle cells isolated from Kaposi's sarcoma
      like skin lesions developed in BK virus (BKV)/tat-transgenic mice. METHODS:
      Kaposi's sarcoma-like spindle cells isolated from the lesions were propagated in
      vitro, and their phenotype was investigated using a panel of antibodies against
      various cell markers and angiogenic factors. Immunofluorescence and Western blot
      techniques were used. RESULTS: We observed co-expression of antigens specific for
      endothelial, smooth muscle and antigen-presenting cells, suggesting that cells
      from the TTB cell line represent poorly differentiated vascular precursors. Since
      TTB cells were derived from highly vascularized skin lesions, it is noteworthy
      that they synthesize a complex mixture of angiogenic factors, including
      fibroblast growth factor-2, vascular endothelial growth factor, placental growth
      factor, and hepatocyte growth factor. Due to their role in invasiveness and
      angiogenesis, we also observed the expression of urokinase plasminogen activator
      (uPA), uPA receptor, and plasminogen activator inhibitor-type 1 by TTB cells.
      CONCLUSIONS: Our results suggest that TTB cells share several features with human
      Kaposi's sarcoma spindle cells and can be a useful in vitro system to study the
      molecular mechanisms involved in Kaposi's sarcoma pathogenesis. Moreover, they
      synthesize a complex mixture of angiogenic factors and are growth-inhibited by
      the anti-angiogenic drug AGM-1470.

PMID- 8883583
TI  - Kaposi's sarcoma in women with AIDS.
AB  - OBJECTIVE: To describe the presentation and incidence of Kaposi's sarcoma (KS) in
      a cohort of women infected with HIV and to compare their clinical characteristics
      with men at the same institution. DESIGN: Retrospective chart and database
      review. SETTING: Adult clinical AIDS program outpatient clinics at a municipal
      teaching hospital. RESULTS: One hundred and seven people with KS were found of
      whom twelve (11.2%) were women. The prevalence of KS in women was 3.6% compared
      with 9.9% among men (P < 0.001). Women born outside the United States were at
      increased risk of developing KS (P < 0.05). At initial KS presentation, no
      difference in HIV stage or CD4 count was found between men and women. Women
      presented with more advanced KS than men, with increased incidence of non
      cutaneous disease (P < 0.001), lymphedema (P < 0.0001), lymph-node disease (P <
      0.0001) and visceral disease (P = 0.03). Women had decreased survival after KS
      diagnosis compared to men, although the difference was not significant (P =
      0.41). CONCLUSIONS: KS is not a rare diagnosis in HIV-infected women followed at
      our institution. Although the increased risk of KS in men is most likely to be
      related to differences in exposure, the sex-related differences in presentation
      and course may be due in part to delay in diagnosis. KS should be considered in
      the spectrum of HIV-related complications in women as well as in men.

PMID- 8883584
TI  - Central brain atrophy in childhood AIDS encephalopathy.
AB  - OBJECTIVE: To determine differential patterns of brain atrophy in pediatric AIDS
      encephalopathy. DESIGN: We measured the bicaudate, bifrontal, and ventricle-brain
      ratio in brain magnetic resonance imaging scans of 42 control children, nine
      children with progressive AIDS encephalopathy, 25 AIDS children without
      progressive encephalopathy, and 23 children with cerebral atrophy of other
      causes. RESULTS: When compared with controls, encephalopathy patients showed
      significantly increased bicaudate and ventricle-brain ratios, but no significant
      increase in bifrontal ratio, whereas children with brain atrophy from causes
      other than AIDS showed increases in all three ratios. CONCLUSION: Children with
      AIDS encephalopathy demonstrate a specific pattern of brain atrophy distinct from
      other etiologies: a central atrophy, primarily affecting the subcortical white
      matter or the basal ganglia regions.

PMID- 8883585
TI  - Combined therapy with zidovudine and L-697,661 in primary HIV infection.
AB  - OBJECTIVE: To decrease viraemia levels in primary HIV infection by using a
      combination of zidovudine (ZDV) and L-697,661. DESIGN: Four primary HIV-infected
      patients were treated for 6 months with ZDV, 250 mg twice daily, in association
      with the non-nucleoside reverse transcriptase inhibitor L-697,661 500 mg three
      times daily. Viraemia, proviral DNA, CD4 and CD8 cell counts were measured
      serially during 18 months. RESULTS: Viraemia decreased to undetectable levels (<
      200 RNA copies/ml) in two patients. A third patient had a marked decrease
      followed by a rebound during therapy; viraemia levels did not vary markedly in
      the fourth patient. A rebound in viraemia levels was observed within 15 days of
      discontinuation of therapy in the three responding patients. Proviral levels
      evolved in parallel with viraemia but were always detectable in all patients. In
      the three patients with an initial decrease of viraemia, CD4 cell counts were
      within the normal range 2 months after initiation of therapy and did not markedly
      decrease after discontinuation of therapy. In the two patients with partial or no
      response of viraemia, mutations associated with low level of resistance to L
      697,661 appeared during treatment. CONCLUSION: A marked decrease of viraemia can
      be achieved in some primary HIV-infected patients with combined therapy. Six
      months of treatment does not prevent a rebound of viraemia, which was observed
      within 15 days of interruption of therapy.

PMID- 8883586
TI  - Effects of perinatal zidovudine on hematopoiesis: a comparison of effects on
      progenitors from human fetuses versus mothers.
AB  - OBJECTIVE: To compare the effects of zidovudine (ZDV) on clonal maturation of
      hematopoietic progenitors obtained from the bone marrow of women of child-bearing
      age with its effects on progenitors obtained from the marrow, liver and blood of
      fetuses. We also sought to determine whether the adverse effects of ZDV on fetal
      hematopoiesis resulted exclusively from an action on progenitors, or also
      involved the inhibition of the production of hematopoietic growth factors.
      PARTICIPANTS: Hematopoietic progenitors were obtained from bone-marrow aspirates
      of seven women of child-bearing age, from the bone marrow and liver of seven mid
      trimester abortuses, and from the umbilical cord blood of seven term infants.
      METHODS: We added increasing concentrations of ZDV to clonal assays of
      hematopoietic progenitors, after which we assayed clonal maturation of
      progenitors, and counted the number of erythrocytes per erythroid clone and the
      number of neutrophils per granulocytic clone. Light-density cell fractions and
      enriched CD34+ progenitor fractions were studied. In other studies we determined
      the effect of increasing concentrations of ZDV on production of granulocyte
      colony-stimulating factor (G-CSF) protein [enzyme-linked immunosorbent assay
      (ELISA)] and mRNA by fetal and maternal monocytes, and on production of
      erythropoietin protein (ELISA) and mRNA by Hep3B cells. RESULTS: Mature erythroid
      progenitors were the most sensitive to the adverse effects of ZDV on clonal
      maturation, and multipotent progenitors were the most resistant. Erythroid
      progenitors from all fetal and neonatal sources were more sensitive to the effect
      of ZDV than those from the bone marrow of adult women. The inhibitory effects
      were explained by an action on CD34+ cells; no effect was observed on production
      of G-CSF or erythropoietin. CONCLUSIONS: We speculate that the low hematocrits of
      neonates delivered after antenatal ZDV treatment are due to reduced clonal
      maturation of erythroid progenitors, and that fetal erythroid progenitors are
      inhibited to a greater extent than maternal progenitors.

PMID- 8883587
TI  - Heterosexual behavior during pregnancy and perinatal transmission of HIV-1. New
      York City Perinatal HIV Transmission Collaborative Study Group.
AB  - OBJECTIVE: To determine the relationship between maternal heterosexual activity
      during pregnancy and perinatal transmission of HIV-1. DESIGN: A retrospective
      analysis of 175 New York City HIV-1-seropositive women enrolled during pregnancy
      or immediately post-partum from 1986 to 1994 in a prospective cohort study.
      METHODS: Frequency of heterosexual intercourse and condom use during pregnancy
      was determined from self-report measures. Unprotected intercourse was defined as
      follows: 'none', consistent condom use or abstinence; 'moderate', inconsistent
      condom use and fewer than 80 episodes of intercourse; and 'high', inconsistent
      condom use and 80 or more episodes. RESULTS: The rate of perinatal HIV-1
      transmission was 9.1% (four out of 44) among women with no unprotected
      intercourse during pregnancy, 22.2% (20 out of 90) among those with moderate
      frequency, and 39.0% (16 out of 41) among those with high frequency (P < 0.01).
      The relative risk (RR) of perinatal transmission was higher among women with
      moderate [RR, 2.4; 95% confidence interval (Cl), 0.9-6.7] and high frequency of
      unprotected sexual intercourse (RR, 4.3; 95% Cl, 1.6-11.8) compared with women
      with no unprotected sexual intercourse. When potential covariates (maternal
      injecting drug use, CD4 lymphocyte count, AIDS, zidovudine use, pelvic
      inflammatory disease or sexually transmitted disease during pregnancy, delivery
      mode, and extreme prematurity) were included in a logistic regression model (n =
      128), the rate of perinatal transmission remained significantly higher among
      women with any unprotected sexual intercourse during pregnancy. CONCLUSIONS: Data
      suggest that unprotected sexual intercourse during pregnancy influences perinatal
      HIV-1 transmission.

PMID- 8883588
TI  - Overall and cause-specific mortality in a cohort of homo-/bisexual men, injecting
      drug users, and female partners of HIV-infected men. Pulmonary Complications of
      Human Immunodeficiency Virus Infection Study Group.
AB  - OBJECTIVE: To study the overall and cause-specific HIV-related mortality in a
      cohort of HIV-seropositive subjects according to transmission category,
      race/ethnicity, sex and severity of immunosuppression. DESIGN: A cohort of 1129
      HIV-seropositive homo-/bisexual men, injecting drug users, and female partners of
      HIV-infected men were enrolled at six centers in San Francisco, Los Angeles,
      Chicago, Newark, Detroit and New York between 1 November 1988 and 1 November
      1989. Subjects were evaluated every 6 months at least until 31 March 1994.
      METHODS: The analyses of overall mortality for the subgroups of interest were
      performed with Kaplan-Meier plots and Cox proportional hazards models. Cause
      specific analyses were performed on the primary cause of death using rates per
      100 person-years of exposure. RESULTS AND CONCLUSIONS: Baseline severity of
      immunosuppression is the strongest predictor of mortality. There were no
      statistically significant differences in overall HIV-related mortality among
      transmission categories, race/ethnicity groups or sexes. There were differences,
      however, in cause-specific mortality among the different risk groups.

PMID- 8883589
TI  - Bridge populations in the spread of HIV/AIDS in Thailand.
AB  - OBJECTIVE: To determine the extent to which men provide a bridge population
      between commercial sex workers (CSW) and the general female population in
      Thailand. DESIGN: Sexual network and serological data were collected from a
      systematic quota sample of low income men and truckers during 1992 in three
      Thailand provinces. Completed sample size was 1075 men aged 17-45 years and 330
      truckers. METHODS: Sexual network information was used to identify those men who
      have sex with both female CSW and non-CSW partners (the 'bridge population'). A
      new method was used for calculating the partner acquisition rate and to establish
      the potential number of women exposed to HIV via inconsistent condom use among
      the bridge population. RESULTS: Approximately 17% of men and 25% of truckers can
      be included in the bridge population. These men are more likely to be HIV
      positive and to have had at least one other sexually transmitted infection in the
      past year (odds ratio, 2.2 and 3.4, respectively). Consistent condom use with CSW
      is less than 30%, and is less than 1% with non-CSW partners. As a result, 30
      women in the general population were potentially exposed to HIV per 100 sexually
      active men in the last year:nine women each additional year. Younger men and
      truckers expose almost twice as many women to HIV; more female peers than wives
      are exposed. CONCLUSION: Bridge populations may be as important as "core groups'
      for the spread of HIV into the general Thai population. Young men and women are
      strategic intervention targets because they have more partners, are more likely
      to be in bridging networks, and are more receptive to condom use.

PMID- 8883590
TI  - HIV/AIDS in New Zealand: an epidemic in decline?
AB  - OBJECTIVE: To describe the AIDS epidemic in New Zealand, and to discuss the
      reasons for an apparent decline in incidence. METHODS: The AIDS Epidemiology
      Group collects information on persons diagnosed with AIDS through a compulsory
      notification system. Data were presented on people diagnosed to the end of 1994,
      and reported by the end of September 1995. RESULTS: The cumulative incidence of
      AIDS in New Zealand was similar to that in some other Western countries, such as
      the United Kingdom, Germany and Sweden, before 1989, but has been declining since
      1989. The epidemic is concentrated among men who have sex with men (89%). The
      median survival after diagnosis with AIDS is 13 months. CONCLUSIONS: The observed
      decline is not likely to be due to reporting delays or changes in reporting or
      diagnostic practices. The major factor was probably a rapid decline in HIV
      incidence among homosexual men a decade ago, and the effective prevention of
      epidemics in other subgroups. The epidemic in New Zealand started later than in
      other countries, enabling an earlier response, and there is evidence of behaviour
      change in high risk groups. Preventive efforts and monitoring must be maintained
      in order to ensure there is no reversal of this decline.

PMID- 8883591
TI  - Mortality impact of AIDS in Abidjan, 1986-1992.
AB  - OBJECTIVES: To quantify the mortality impact of AIDS in the city of Abidjan (Cote
      d'Ivoire) by a full scale analysis of mortality trends before and after the onset
      of the epidemic. DESIGN: Data on deaths registered in the 10 vital registration
      centers of the city between 1973 and 1992, and data on causes of deaths in the
      four public hospitals were coded and investigated. Data on deaths were compared
      with census data in order to compute death rates. METHODS: Life tables were
      computed for each of the 20 years of the study. The trends in death rates were
      analysed during the 10 years before the onset of the AIDS epidemic (1973-1982)
      and compared with the changing death rates in the following 10 years (1983-1992).
      Deaths attributable to AIDS were defined as those in excess of the original
      trends. The evolution in the number of deaths in the hospital allowed an analysis
      by cause of death. RESULTS: There was a marked increase in death rates starting
      in 1986, date of the first diagnosed AIDS cases in the city. This increase was
      significant for both sexes, but more pronounced among men. It was concentrated
      primarily among young adults (aged 25-44 years) and among older children (aged 5
      14 years), and most of it was considered to be attributable to AIDS and related
      infections, tuberculosis in particular. When data were cumulated from 1986 to
      1992, approximately 25,000 persons were estimated to have died of AIDS.
      CONCLUSIONS: The high number of AIDS deaths estimated in Abidjan underlines the
      heavy toll already paid by African populations, and calls for intensive action.

PMID- 8883592
TI  - From biology to sexual behaviour--towards the prevention of mother-to-child
      transmission of HIV.

PMID- 8883593
TI  - Potential heterosexual Kaposi's sarcoma-associated herpesvirus transmission in a
      couple with HIV-induced immunodepression and with Kaposi's sarcoma and
      multicentric Castleman's disease.

PMID- 8883594
TI  - Prevalence of zidovudine-resistant HIV-1 among rapid progressors.

PMID- 8883595
TI  - Improvement of the CD4 cell count after alcohol withdrawal in HIV-positive
      alcoholic patients.

PMID- 8883596
TI  - Physical breaks in the placental trophoblastic surface: significance in vertical
      transmission of HIV.

PMID- 8883597
TI  - Detection of asymptomatic Pneumocystis carinii infection by polymerase chain
      reaction: predictive for subsequent pneumonia.

PMID- 8883598
TI  - Retinal toxicity associated with didanosine in HIV-infected adults.

PMID- 8883599
TI  - Famciclovir in AIDS-related acute retinal necrosis.

PMID- 8883600
TI  - Treatment of isosporiasis with combined albendazole and ornidazole in patients
      with AIDS.

PMID- 8883602
TI  - 5-Hydroxytryptamine deficits in the caudate nucleus in AIDS.

PMID- 8883601
TI  - Painful neuropathy of the lateral cutaneous nerve of the thigh in patients with
      AIDS: successful treatment by injection with bupivacaine and triamcinolone.

PMID- 8883603
TI  - Virology.

PMID- 8883604
TI  - HIV cDNA integration: molecular biology and inhibitor development.

PMID- 8883605
TI  - Genetic variability of HIV-1.

PMID- 8883606
TI  - Viral and cellular determinants of HIV-1 replication in macrophages.

PMID- 8883607
TI  - Murine and simian retrovirus models: the threshold hypothesis.
AB  - By considering the dynamic relationship between retroviruses and their hosts, we
      have developed a unifying hypothesis to explain such disparate clinical phenomena
      as differential pathogenicity of a given virus in adults and neonates, transient
      infection with clearance of provirus-containing cells, long-term non-progression
      and vaccine effects of fully pathogenic viruses. The threshold hypothesis
      predicts that an opportunity exists during acute retroviral infection to
      influence the ultimate clinical outcome: if virus replication is kept below
      threshold by any means, including drug therapy or passive immunoprophylaxis with
      neutralizing antibodies, the host will prevail and win the race.

PMID- 8883608
TI  - Epidemiology.

PMID- 8883609
TI  - HIV/AIDS in Latin America and the Caribbean: an update.

PMID- 8883610
TI  - The epidemiology of HIV-associated Kaposi's sarcoma: the unraveling mystery.
AB  - Unraveling the mysteries associated with the etiology of KS is of tremendous
      public health significance. Whereas the introduction of prophylaxis has led to a
      decreased incidence of Pneumocystis carinii pneumonia, the incidence of KS has
      remained relatively stable and treatment of the HIV-infected KS patient remains a
      challenge. The last year has brought forth significant breakthroughs in KS
      research. Although KSHV has only recently been described, rapid progress is being
      made in understanding the role of this virus in the pathophysiology of the
      various forms of KS. It is too early to conclude whether KSHV is the elusive 'KS
      cofactor' or if all forms of KS share a common etiology, but it appears to be the
      single most plausible agent to be identified to date. Since all cancers are
      multifactorial in origin, it is likely that other host, environmental and
      possibly other viral cofactors could influence the risk of developing KS. The
      search for such cofactors must continue. Even if KSHV plays a central role, the
      exact mechanisms by which HIV and KSHV may interact to induce KS lesions, the
      tendency for KS to occur among homosexual men relative to other HIV transmission
      groups, and the reasons for the aggressive course of this neoplasm in HIV
      infected persons remain to be determined. If a causal association can be
      established, KSHV could provide a model for the understanding of virus-induced
      neoplasia, like its cousin EBV. Although important questions regarding the
      specificity and temporality of KSHV and KS remain unanswered, the development and
      application of a sensitive serodiagnostic tool in longitudinal studies will be a
      crucial next step.

PMID- 8883611
TI  - The role of host genetics in the natural history of HIV-1 infection: the needles
      in the haystack.

PMID- 8883612
TI  - Gender, ethnicity and transmission category variation in HIV disease progression.

PMID- 8883613
TI  - Probabilities of sexual HIV-1 transmission.

PMID- 8883614
TI  - Vaccines and immunology.

PMID- 8883615
TI  - Cellular immune responses to HIV-1 in progressive and non-progressive infections.

PMID- 8883616
TI  - The role of the humoral immune response in HIV infection.

PMID- 8883617
TI  - Antigenic determinants on HIV-1 envelope glycoproteins: a dickens of a time with
      oligomer twist.

PMID- 8883618
TI  - Primate models for AIDS vaccine development.

PMID- 8883619
TI  - HIV vaccine development: from basic research to human trials.

PMID- 8883620
TI  - Clinical treatment.

PMID- 8883621
TI  - Newer nucleosides: lamivudine and stavudine.

PMID- 8883622
TI  - Combination therapy: look before you leap.

PMID- 8883623
TI  - HIV protease inhibitors.

PMID- 8883624
TI  - Immune-based therapies in HIV infection: recent developments.
AB  - A wide variety of different immunologic approaches have been evaluated as
      potential therapies for HIV disease. Whether any of these approaches will play a
      role in clinical management will require the completion of the appropriate
      clinical trials. Importantly, all clinical trials present opportunities to
      evaluate aspects of the pathogenesis of HIV infection that are perhaps
      unevaluable in vitro. Clinical trials of antiretroviral drugs have defined the
      dynamics of HIV replication [37,38]. The complexities and heterogeneity of the
      immune system and particularly its responses to HIV are being unveiled in the
      setting of clinical trials of immune-based therapies. Truly effective treatments
      for HIV will result in long-term preservation of immune function allied to
      control of virus replication in infected individuals. Immune-based therapy might
      well play a significant role in such strategies.

PMID- 8883625
TI  - Multiple opportunistic infection prophylaxis.

PMID- 8883626
TI  - Kaposi's sarcoma: relationship to a novel herpesvirus and advances in therapy.

PMID- 8883627
TI  - Social, cultural and political aspects.

PMID- 8883628
TI  - A review of national AIDS-related behavioral surveys.

PMID- 8883629
TI  - Social research on sexuality: contextual and interpersonal approaches.

PMID- 8883630
TI  - Faithful but fearful: reducing HIV transmission in stable relationships.

PMID- 8883631
TI  - The socioeconomic impact of AIDS in sub-Saharan Africa.

PMID- 8883632
TI  - Stress and burnout in HIV/AIDS carers.

PMID- 8883633
TI  - Estimates and trends of the HIV/AIDS epidemic.

PMID- 8883634
TI  - Interobserver variability in angiographic measurement and morphologic
      characterization of intracranial aneurysms: a report from the International Study
      of Unruptured Intracranial Aneurysms.
AB  - PURPOSE: To determine the variability in assessment of the principal inherent
      characteristics of intracranial aneurysms through the evaluation of interobserver
      variability for material with uniform quality. METHODS: Blinded interpretations
      of a single set of cerebral arteriograms of 55 aneurysms were evaluated by
      several statistical approaches. RESULTS: Excellent correlations were found for
      the detection and measurement of aneurysms after adjusting for geometric
      distortion caused by magnification. Progressively decreasing correspondence was
      found for factors that characterized morphology, including, in order,
      determination of margins, assessment of accessory appendages, and identification
      of a neck. DISCUSSION: Correction for geometric distortion was the most critical
      factor that influenced uniform measurement of size. Standards for measurement and
      morphologic characteristics were subsequently established for use in the
      International Study of Unruptured Intracranial Aneurysms.

PMID- 8883635
TI  - Flow dynamics in a fatal aneurysm of the basilar artery.
AB  - PURPOSE: To examine the flow dynamics in a fatal aneurysm of the basilar artery
      in humans. METHODS: We made transparent elastic replicas of the vertebrobasilar
      arteries of an elderly patient who died of a ruptured aneurysm in the basilar
      artery. Using non-Newtonian fluid, physiological pulsatile flow volumes and
      profiles, and isobaric dyes and particles, we observed and recorded the
      slipstreams as they entered the aneurysm while changing relative flow in the
      vertebral arteries. Finally, we placed clips on the aneurysm, leaving residuals
      (or dog-ears), and observed the slipstreams. RESULTS: The aneurysm originated
      laterally from the greater curvature of a tortuous basilar artery, measured 19 x
      11 x 12 mm, and had a Murphy's teat at the apex, the rupture site. The neck
      measured 10 x 4 mm, about the diameter of the basilar artery. Slipstreams joined
      at the confluence of the vertebral arteries, formed helical flow patterns, and
      entered the aneurysm violently, striking the apex. They then passed proximally
      around the sac walls, then centrally, and finally reentered the basilar artery to
      pass distally. Altering the relative flows in the vertebral arteries could modify
      and prevent slipstream flow into the aneurysm. When a dog-ear was created by
      incorrect placement of an aneurysm clip, slipstreams entered only dog-ears that
      lay distal to the clip. Correctly placed clips excluded the aneurysm from the
      circulation, but did not return the flow dynamics to normal. CONCLUSION: High
      velocity slipstreams strike aneurysms at their rupture site and have an impact on
      distal but not proximal dog-ears. Modifying relative flow may prevent aneurysmal
      filling. Further, a knowledge of flow dynamics may allow us to predict which
      aneurysms are at risk of enlarging and rupturing, and may help guide proper
      therapy.

PMID- 8883636
TI  - Unusual manifestation of a vein of Galen malformation: value of CT angiography.
AB  - We describe a neonate with aneurysmal dilatation of the vein of Galen with
      arteriovenous fistulous sites located at the superior vermian vein. Helical CT
      angiography was useful for evaluating the anomalous vessels.

PMID- 8883637
TI  - Craniopharyngioma: radiologic and histologic findings and recurrence.
AB  - PURPOSE: To identify the CT and MR characteristics of craniopharyngiomas, to
      evaluate the histologic types of craniopharyngioma, and to compare the
      radiologic/histologic appearance and type of therapy with tumor recurrence.
      METHODS: We reviewed the records of 45 patients with craniopharyngiomas for which
      surgical specimens (n = 45), preoperative MR or CT studies (n = 27), or other MR
      or CT studies or reports (n = 18) were available. Radiologic appearance,
      histologic morphology, treatment, and tumor recurrence were studied. RESULTS:
      Adamantinomatous epithelium was found in 40 of 45 surgical specimens, keratin in
      34 of 45, and squamous epithelium in 11 of 45. A continuum of mixed morphology
      rather than distinct subtypes of tumors was found. The radiologic appearance did
      not correlate with the histologic features. No statistically significant
      difference was found between children and adults with respect to tumor size,
      calcification, histology, or tumor recurrence. Patients treated with radiation
      after subtotal resection had far fewer tumor recurrences (n = 3) than patients
      treated with surgery alone (n = 18). CONCLUSION: Craniopharyngiomas could not be
      divided into distinct histologic types. No differentiating radiologic or
      histologic characteristics could be established for craniopharyngiomas in
      children versus adults. Radiation treatment was strongly associated with tumor
      regression or lack of recurrence.

PMID- 8883638
TI  - Craniopharyngioma: prognostic importance of histologic features.

PMID- 8883639
TI  - The effect of arteriovenous malformations on the distribution of intracerebral
      arterial pressures.
AB  - PURPOSE: To examine the distribution of arterial hypotension surrounding
      arteriovenous malformations (AVMs) using a standardized system of vascular zones.
      METHODS: Mean arterial pressures were recorded during superselective cerebral
      angiography in 96 patients with AVMs (before they underwent liquid polymer
      embolization) with the use of a system of vascular zones: E = extracranial
      internal carotid or vertebral artery; I = intracranial internal carotid or
      basilar artery; T = transcranial Doppler insonation site (A1, P1, M1); H =
      halfway to feeder, perfusing normal tissue and shunt; and F = feeder at site of N
      butyl cyanoacrylate injection. Distal arterial pressure was measured
      contralateral to the AVM in an additional 12 patients (zone Hc). RESULTS: Zone
      pressures (mm Hg +/- SD) were E = 76 +/- 16, I = 69 +/- 15, T = 59 +/- 16, H = 47
      +/- 13, and F = 39 +/- 15 mm Hg. Vessel/systemic ratios for the zones were E =
      0.97 +/- 0.05, I = 0.86 +/- 0.08, T = 0.75 +/- 0.12, H = 0.61 +/- 0.13, and F =
      0.50 +/- 0.18. Measurements were obtained in 29 patients in all five zones and
      all had similar mean values. Zone Hc pressure was 66 +/- 17 mm Hg and the ratio
      was 0.78 +/- 0.12, both greater than zone H values. CONCLUSION: Using a
      standardized system of anatomic vascular zones, we found a progressive and
      significant decrease in intracerebral arterial pressure in patients with AVMs
      that proceeded from the circle of Willis to the nidus. Large areas of parenchyma
      sharing the same parent arterial supply may be subject to chronic hypotension.

PMID- 8883640
TI  - Arteriovenous malformation animal model for radiosurgery: the rete mirabile.
AB  - PURPOSE: To study the effects of single-dose radiation on the porcine rete
      mirabile, a tangle of microvessels that mimics human arteriovenous malformations
      of the brain. METHODS: Eight retia mirabilia received a single dose of radiation
      under stereotactic location with digital angiography and CT. The following doses
      were applied: 20, 30, 40, 50, 60, 70, 80, and 90 Gy. The animals were followed up
      for a period of 7 months. Findings at neurologic examination, serial angiography,
      and histopathologic examination were analyzed. RESULTS: Progressive occlusion as
      observed by angiography corresponded to the histopathologic finding of intimal
      hyperplasia; that is, marked thickening of the vessel wall, progressing to
      occlusion of the vascular lumen, and associated thrombosis. A direct dose
      response was noted for these changes. Neurologic findings were related to the
      dose distribution and to histologic findings in structures adjacent to the rete
      mirabile. CONCLUSION: The rete mirabile is an excellent model by which to study
      the radiologic and histologic effects of single-dose radiation to the
      microvasculature of the central nervous system.

PMID- 8883641
TI  - Endovascular treatment of arteriovenous malformations with selective intranidal
      occlusion by detachable platinum electrodes: technical feasibility in a swine
      model.
AB  - The technical feasibility of selective intranidal endovascular occlusion of
      experimental arteriovenous malformations with detachable superfine platinum
      electrodes was assessed in a swine model. The delivery and release of electrodes
      were performed within normal carotid retia mirabilia, the faster-flowing nidus
      (bilateral retia) of a carotid-jugular fistula-type model of an arteriovenous
      malformation, and a small-caliber H-type direct arteriovenous fistula.
      Controllable atraumatic placement of the electrodes was possible deep within each
      rete and in the middle of the fistula. The devices were soft and flexible,
      allowing them to conform to the tight turns and branches of rete vessels. Marked
      diminution of flow was achieved by release of multiple devices within each rete.
      Migration of the electrode occurred when detached within the larger-caliber
      arteriovenous fistula. The main advantages of this technique appear to be the
      controlled delivery and assured release of an occlusive radiopaque embolic agent
      within the nidus.

PMID- 8883642
TI  - Imaging findings of the developing temporal bone in fetal specimens.
AB  - PURPOSE: To trace the development of the normal fetal temporal bone by means of
      plain radiography, MR, and CT. METHODS: Eighteen formalin-fixed fetal specimens,
      13.5 to 24.4 weeks' gestational age, were examined with a mammographic plain film
      technique, CT, and MR imaging at 1.5 T. Temporal bone development and
      ossification were assessed. RESULTS: The membranous labyrinth grows with amazing
      rapidity and attains adult size by the middle of the gestation period. The
      cochlea, vestibule, and semicircular canals are very prominent and easily
      recognized on MR images. The otic capsule develops from a cartilage model.
      Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from
      multiple ossification centers that replace the cartilaginous framework. The
      mastoid, internal auditory canal, vestibular aqueduct, and external auditory
      canal continue to grow after birth. CONCLUSION: The study of fetal developmental
      anatomy may lead to a better understanding of congenital disorders of the ear.
      Faster MR scanning techniques may provide a method for in utero evaluation of the
      fetal temporal bone.

PMID- 8883643
TI  - Hearing, II: the retrocochlear auditory pathway.

PMID- 8883644
TI  - Radiologic-clinical correlation. One-and-a-half syndrome associated with
      cheirooral syndrome.

PMID- 8883645
TI  - Proton MR spectroscopy of squamous cell carcinoma of the upper aerodigestive
      tract: in vitro characteristics.
AB  - PURPOSE: To determine the ability of in vitro high-field-strength proton MR
      spectroscopy to differentiate squamous cell carcinoma of the upper aerodigestive
      tract from uninvolved muscle. METHODS: Surgical specimens of squamous cell
      carcinoma arising from the upper aerodigestive tract (n = 18) and from muscle (n
      = 13) were examined in vitro using high-field (11 T) proton MR spectroscopy. The
      peak heights of choline and creatine were measured for tumor and muscle at echo
      times of 136 and 272. The choline/creatine (Cho/Cr) ratio was compared between
      tumor and normal tissue for each echo time. Student's t test was used to
      determine whether a significant difference existed between proton MR
      spectroscopic measurements of the Cho/Cr ratio for tumor and muscle. RESULTS: The
      mean Cho/Cr ratio was consistently higher in tumor than in muscle at all echo
      times; however, statistically significant differences between tumor and muscle
      were identified only at longer echo times (136 and 272). CONCLUSION: The Cho/Cr
      peak height ratio can be used to differentiate tumor from muscle in vitro (at 11
      T).

PMID- 8883646
TI  - Calcified amyloidoma of the larynx.
AB  - We describe a case of laryngeal amyloidoma in a 39-year-old man in whom CT
      examination disclosed a calcifield soft-tissue mass arising in the epiglottis.
      The presence of focal calcifications suggested a cartilaginous tumor.

PMID- 8883647
TI  - MR of intracranial extension of nasopharyngeal teratoma.

PMID- 8883648
TI  - Anatomic evaluation of the circle of Willis: MR angiography versus intraarterial
      digital subtraction angiography.
AB  - PURPOSE: To evaluate the reliability of source images and maximum intensity
      projection images of MR angiography in showing the arterial segments of the
      circle of Willis. METHODS: In 62 patients, 526 arterial segments of the circle of
      Willis were determined to be present, partially present, or absent by blinded
      observers evaluating MR angiographic source images and maximum intensity
      projection images. Vessel diameter was measured on source images. These results
      were then compared with the results from intraarterial digital subtraction
      angiography. RESULTS: MR angiographic maximum intensity projection images had a
      sensitivity of 87% and a specificity of 88% and MR angiographic source images had
      a sensitivity of 89% and a specificity of 63% in depicting the presence of a
      vessel segment. The positive predictive value of an arterial segment with a
      diameter of at least 1 mm was 99%. CONCLUSION: MR angiography is a sensitive
      technique for detecting the anatomy of the circle of Willis. Maximum intensity
      projection images are more specific than source images. An arterial segment with
      a diameter of at least 1 mm on the source image is almost always present and
      patent.

PMID- 8883649
TI  - Specificity of MR angiography as a confirmatory test of carotid artery stenosis.
AB  - PURPOSE: To estimate from available literature the specificity (true-negative
      rate) of MR angiography for detecting severe carotid artery stenoses when applied
      as a confirmatory test after screening with duplex Doppler sonography. METHODS:
      We reviewed the pertinent MR angiographic literature published between 1990 and
      1994 and recalculated the specificity of MR angiography after deleting from the
      database results for normal vessels and for vessels with mild and moderate
      stenoses, since the study of these vessels is not germane to an exploration of
      the utility of MR angiography as a confirmatory test. RESULTS: Seventeen articles
      provided data for our analysis. We divided vessels into four categories on the
      basis of data supplied within each article. Seven of the articles provided data
      that could be configured to match the categories used in the North American
      Symptomatic Carotid Endarterectomy Trial (NASCET). In one study, the criterion of
      severe stenosis was more than 70% construction, but the moderate category was
      limited to stenoses of 50% to 69%. The remaining series defined severe stenoses
      as more than 80% (four series), more than 75% (two series), or more than 60%
      (three series) constriction. The stated specificity of MR angiography ranged from
      64% to 100%. Before revision, 15 of 17 articles had stated specificity values
      above 75%. Our recalculated values ranged from 18% to 100%. Only seven of 17
      studies would have had MR angiographic specificity of greater than 75%. Nine of
      17 articles would have had specificities of less than 60%. For all articles
      specifically identifying vessels with false-positive findings at sonography, the
      specificity of MR angiography was 16%. CONCLUSION: To base specificity values for
      MR angiography as a confirmatory test of carotid artery stenosis on studies that
      include nondiseased vessels incurs spectrum bias. The actual specificity for MR
      angiography as a confirmatory test remains unknown, but it is lower than that
      reported in the literature.

PMID- 8883650
TI  - Adult cerebrovascular disease: role of modified rapid fluid-attenuated inversion
      recovery sequences.
AB  - PURPOSE: To compare a rapid fluid-attenuated inversion-recovery (FLAIR) sequence
      with T1-weighted, fast spin-echo proton density-weighted, and T2-weighted images
      in the evaluation of cerebrovascular disease. METHODS: All patients underwent
      standard T1-, proton density-, and T2-weighted fast spin-echo and fast FLAIR MR
      imaging at 1.5 T. Images were compared for lesion size, location, and
      conspicuity. RESULTS: Forty-five infarctions were identified on T2-weighted and
      fast FLAIR sequences. Lesion size was comparable on the proton density-weighted,
      fast T2-weighted, and fast FLAIR sequences, although lesion conspicuity was
      superior on the fast FLAIR images in 43 (96%) of the lesions. Associated
      periventricular and pontine hyperintensities were more extensive on the fast
      FLAIR images. CONCLUSION: Our modified fast FLAIR technique provided improved
      conspicuity of infarctions and white matter disease as compared with T1-, proton
      density-, and T2-weighted spin-echo images, and a reduced scan time compared with
      conventional FLAIR sequences in patients with cerebrovascular disease.

PMID- 8883651
TI  - Intractable temporal lobe epilepsy: comparison of positron emission tomography
      with qualitative and quantitative MR.
AB  - PURPOSE: To compare the ability of qualitative fludeoxyglucose F 18 positron
      emission tomography (QPET), qualitative MR imaging (QMR), and quantitative MR
      imaging with hippocampal formation volumetric assessment (HV MR) to lateralize
      the seizure focus in patients with temporal lobe epilepsy. METHODS: Sixteen
      consecutive patients undergoing presurgical examination for temporal lobe
      seizures had QPET, QMR, and HV MR. The presence of temporal lobe epilepsy was
      confirmed by Engel class I or II outcomes at 1-year postoperative follow-up
      examinations. A QPET, QMR, or HV MR study was considered to be lateralizing if it
      matched the side of the seizure focus, nonlateralizing if it did not lateralize
      the seizure focus to either temporal lobe, or incorrectly lateralizing if it
      lateralized the seizure focus to the incorrect side. RESULTS: Of 16 patients with
      proved temporal lobe seizures, QPET was correctly lateralizing in nine (56%),
      nonlateralizing in six (37.5%), and incorrectly lateralizing in one (6%). QMR was
      correctly lateralizing in six (37.5%), nonlateralizing in six (37.5%), and
      incorrectly lateralizing in four (25%). HV MR was correctly lateralizing in all
      16 patients (100%). Age at onset, seizure duration, and total number of seizures
      did not correlate with QPET, QMR, and HV MR lateralization. CONCLUSIONS: Our
      results show that each imaging technique yields useful information for seizure
      lateralization in temporal lobe epilepsy and that HV MR yields considerably more
      information that QPET or QMR.

PMID- 8883652
TI  - Normal appearance of arachnoid granulations on contrast-enhanced CT and MR of the
      brain: differentiation from dural sinus disease.
AB  - PURPOSE: To determine the imaging appearance and frequency with which arachnoid
      granulations are seen on contrast-enhanced CT and MR studies of the brain.
      METHODS: We retrospectively reviewed 573 contrast-enhanced CT scans and 100
      contrast-enhanced MR studies of the brain for the presence of discrete filling
      defects within the venous sinuses. An anatomic study of the dural sinuses of 29
      cadavers was performed, and the location, appearance, and histologic findings of
      focal protrusions into the dural sinus lumen (arachnoid granulations) were
      assessed and compared with the imaging findings. RESULTS: Discrete filling
      defects within the dural sinuses were found on 138 (24%) of the contrast-enhanced
      CT examinations. A total of 168 defects were found, the majority (92%) within the
      transverse sinuses. One third were isodense and two thirds were hypodense
      relative to brain parenchyma. Patients with filling defects were older than
      patients without filling defects (mean age, 46 years versus 40 years). Discrete
      intrasinus signal foci were noted on 13 (13%) of the contrast-enhanced MR
      studies. The foci followed the same distribution as the filling defects seen on
      CT scans and were isointense to hypointense on T1-weighted images, variable in
      signal on balanced images, and hyperintense on T2-weighted images. Transverse
      sinus arachnoid granulations were noted adjacent to venous entrance sites in 62%
      and 85% of the CT and MR examinations, respectively. Arachnoid granulations were
      found in 19 (66%) of the cadaveric specimens, in a similar distribution as that
      seen on the imaging studies. CONCLUSION: Discrete filling defects, consistent
      with arachnoid granulations, may be seen in the dural sinuses on 24% of contrast
      enhanced CT scans and on 13% of MR studies. They are focal, well-defined, and
      typically located within the lateral transverse sinuses adjacent to venous
      entrance sites. They should not be mistaken for sinus thrombosis or intrasinus
      tumor, but recognized as normal structures.

PMID- 8883653
TI  - Comparison of two MR sequences for the detection of multiple sclerosis lesions in
      the spinal cord.
AB  - PURPOSE: To compare cardiac-triggered dual-echo spin-echo and magnetization
      transfer-prepared gradient-echo (MT-GE) MR imaging in the detection of multiple
      sclerosis (MS) lesions in the spinal cord. METHODS: The cervical spinal cord in
      20 patients with MS and in nine healthy volunteers was examined with spin-echo
      and MT-GE MR imaging. Sagittal images were scored for number of lesions,
      certainty about lesions, image quality, and visual hindrance by artifacts in
      random order by two radiologists separately and in a blinded manner. RESULTS: In
      one healthy volunteer, a lesion was seen on images obtained with both images.
      Lesion/cord contrast-to-noise ratio was equal on both the MT-GE and T2-weighted
      spin-echo images. MT-GE images showed better image quality and fewer artifacts
      than the spin-echo images did. The readers found approximately the same number of
      lesions. However, the number of definite lesions was higher for the spin-echo
      sequence than for the MT-GE sequence. One reader found 45 definite lesions with
      spin-echo and 34 definite lesions with MT-GE. For the other reader, these numbers
      were 37 (spin-echo) and 31 (MT-GE). On the spin-echo images, 90% of the patients
      were considered to have definite lesions; on the MT-GE images, the readers found
      definite lesions in 65% (reader 1) and in 70% (reader 2) of the patients.
      CONCLUSION: Image quality was better with the MT-GE technique than with the spin
      echo technique, and lesion/cord contrast-to-noise ratio on the MT-GE images was
      equal to that of T2-weighted spin-echo images. However, for detecting spinal cord
      MS lesions in the sagittal plane, the spin-echo images were preferred to the MT
      GE images.

PMID- 8883654
TI  - Proton MR spectroscopy and magnetization transfer ratio in multiple sclerosis:
      correlative findings of active versus irreversible plaque disease.
AB  - PURPOSE: To characterize plaques of multiple sclerosis (MS) using both proton MR
      spectroscopy and magnetization transfer (MT) imaging. METHODS: The magnetization
      transfer ratio (MTR) was calculated from two series of three-dimensional gradient
      recalled acquisition in the steady state (GRASS) images obtained with and without
      an MT saturation pulse. Proton spectra were acquired using the point-resolved
      spectroscopy (PRESS) sequence with a voxel size of 1.5 x 1.5 x 1.5 cm3. A total
      of 28 spectra were obtained in 13 patients who had clinically definitive MS. The
      spectra were analyzed together with the MTR. RESULTS: A positive relationship was
      found between the N-acetylaspartate (NAA)/creatine (Cr) ratio and the MTR in MS
      plaques, whereas no significant correlation was found between the metabolite
      ratios and the signal intensity on fast spin-echo T2-weighted MR images.
      CONCLUSION: Small changes in the MTR of MS plaques relative to the MTR of normal
      white matter may reflect inflammatory changes and edema, whereas larger changes
      in MTR correlate with decreased NAA/Cr ratio and therefore suggest demyelination
      and irreversible damage from chronic MS plaques.

PMID- 8883655
TI  - Intracranial dural arteriovenous fistulas with spinal venous drainage: relation
      between clinical presentation and angiographic findings.
AB  - PURPOSE: To investigate why some patients with an intracranial dural
      arteriovenous fistula (DAVF) with spinal venous drainage have myelopathy and
      others do not. METHODS: We reviewed the clinical and radiologic data for 12
      patients who had a DAVF with spinal venous drainage diagnosed at our institutions
      from 1982 to 1995. RESULTS: Six patients had progressive spinal cord indications
      of disease (patients with myelopathy) and six others (patients without
      myelopathy) had cerebral indications (five had intracranial hemorrhage and one
      had a seizure). Cerebral angiography showed a posterior fossa DAVF with spinal
      venous drainage in all cases. The clinical presentation of DAVFs with spinal
      venous drainage was compared with the extent of the drainage. In patients without
      myelopathy, the spinal venous drainage exited the intradural canal via the
      cervical medullary-radicular veins and was therefore limited to the cervical
      perimedullary veins. In patients with myelopathy, no medullary-radicular vein was
      seen, and the venous drainage descended along the perimedullary veins of the
      entire spinal cord toward the conus medullaris. CONCLUSION: We found an exact
      relation between clinical presentation and venous drainage of DAVFs with spinal
      venous drainage. Patients had no myelopathy when the venous drainage was limited
      to the cervical cord; myelopathy was present when the venous drainage descended
      toward the conus medullaris.

PMID- 8883656
TI  - Spinal cord lesions in patients with multiple sclerosis: comparison of MR pulse
      sequences.
AB  - PURPOSE: To compare T2-weighted conventional spin-echo (CSE), fast spin-echo
      (FSE), shorttau inversion recovery (STIR) FSE, and fluid-attenuated inversion
      recovery (FLAIR) FSE sequences in the assessment of cervical multiple sclerosis
      plaques. METHODS: Twenty patients with clinically confirmed multiple sclerosis
      and signs of cervical cord involvement were examined on a 1.5-T MR system.
      Sagittal images of T2-weighted and proton density-weighted CSE sequences, T2
      weighted FSE sequences with two different sets of sequence parameters, STIR-FSE
      sequences, and FLAIR-FSE sequences were compared by two independent observers. In
      addition, contrast-to-noise measurements were obtained. RESULTS: Spinal multiple
      sclerosis plaques were seen best on STIR-FSE images, which yielded the highest
      lesion contrast. Among the T2-weighted sequences, the FSE technique provided
      better image quality than did the CSE technique, but lesion visibility was
      improved only with a repetition time/echo time of 2500/90; parameters of 3000/150
      provided poor lesion contrast but the best myelographic effect and overall image
      quality. CSE images were degraded by prominent image noise; FLAIR-FSE images
      showed poor lesion contrast and strong cerebrospinal fluid pulsation artifacts.
      CONCLUSIONS: The STIR-FSE sequence is the best choice for assessment of spinal
      multiple sclerosis plaques. For T2-weighted FSE sequences, shorter echo times are
      advantageous for spinal cord imaging, long echo times are superior for
      extramedullary and extradural disease. FLAIR-FSE sequences do not contribute much
      to spinal imaging for multiple sclerosis detection.

PMID- 8883657
TI  - Infarcted spinal schwannoma: an unusual MR finding.
AB  - We present a case of infarcted schwannoma of the thoracic spine in a patient with
      acute cord compression. MR images did not enhance after contrast administration,
      which is highly atypical for schwannoma, but was in keeping with the pathologic
      findings in this case.

PMID- 8883659
TI  - MR of the submandibular gland: normal and pathologic states.
AB  - PURPOSE: To evaluate the MR appearance of normal and pathologic states of the
      submandibular gland. METHODS: MR images of 22 healthy subjects and 21 patients
      with histopathologically confirmed disorders of the submandibular gland (five
      pleomorphic adenomas, two hemangiomas, two malignant lymphomas, one adenoid
      cystic carcinoma, one squamous cell carcinoma, and 10 cases of sialadenitis) were
      reviewed. RESULTS: All normal submandibular glands showed higher signal intensity
      than surrounding muscle but lower intensity than fat on T1-weighted and T2
      weighted images. Postcontrast images showed moderate enhancement of the gland.
      All the tumors had lower signal intensity than the normal submandibular gland on
      T1-weighted images and had intermediate to high (n = 8) or high (n = 3) signal
      intensity relative to the normal submandibular gland on T2-weighted images. Six
      of seven benign tumors were well defined, and three of four malignant tumors were
      poorly defined. In all cases of sialadenitis, the submandibular gland showed
      diffusely different signal intensities from the normal gland on both T1-weighted
      and T2-weighted images. Eight cases of chronic sialadenitis showed lower T2
      weighted signal intensities than the normal gland, and this can be explained
      histopathologically by marked fibrosis and cellular infiltration. CONCLUSIONS: MR
      imaging can show the presence, extent, margins, and signal intensity changes of
      pathologic conditions of the submandibular gland.

PMID- 8883658
TI  - Hydroxyapatite cement to repair skull base defects: radiologic appearance.
AB  - PURPOSE: To describe the radiologic appearance of hydroxyapatite cement (HAC),
      which, when mixed with liquid, forms a paste that can be contoured to osseous
      defects and, over time, becomes "osseointegrated" (native bone grows into the
      pores of the HAC and forms a strong chemical bond with the substance). METHODS:
      Between March 1992 and June 1993, 24 adults (16 men, eight women) underwent skull
      base surgery that included reconstruction or closure with HAC. Fourteen patients
      had HAC placed in the paranasal sinuses or facial bones, and 10 had HAC placed in
      the mastoid cavity. RESULTS: HAC is homogeneously radiopaque on CT scans and
      plain radiographs. Large amounts (ablating a frontal sinus or mastoid air cells)
      are readily seen; small amounts are inconspicuous. On MR images, HAC is a signal
      void. Infected HAC in one patient was surrounded be enhancing soft tissue on MR
      images, separated from native bone by an irregular radiolucent cleft on CT scans.
      CONCLUSIONS: HAC is a valuable addition to the surgical armamentarium for the
      repair of skull base defects. More experience will determine the time course for
      normal osseointegration, as well as the typical appearance of infection.

PMID- 8883660
TI  - Malignant plasmacytoma appearing as invasive paranasal sinus disease after
      cardiac transplantation.
AB  - Invasive plasmacytoma appearing as a mass in the paranasal sinuses developed in
      two patients after cardiac transplantation. Radiographic findings included a
      sinus mass with bony invasion and expansion. The findings were radiographically
      indistinguishable from common malignant neoplasms and aggressive infectious
      processes. Malignant plasmacytoma should be considered in the differential
      diagnosis of invasive paranasal sinus masses in chronically immunosuppressed
      patients.

PMID- 8883661
TI  - MR in children with L-carnitine deficiency.
AB  - PURPOSE: To describe the MR imaging findings in five children with proved L
      carnitine deficiency. METHODS: MR imaging studies (five without contrast, two
      with contrast) were obtained in five children (mean age, 9 years) who presented
      with stroke symptoms and who proved to have L-carnitine deficiency as established
      by serum levels. RESULTS: In three of five patients, infarctions were confined to
      arterial distributions; one patient had a hemorrhagic infarction in one
      frontoparietal region; and one patient had only nonspecific periventricular white
      matter T2 hyper-intensities. Serum L-carnitine levels normalized after
      correction; sequelae included seizures in two patients, hemiparesis in one
      patient, normal outcome in one patient, and death in one patient. CONCLUSION: L
      Carnitine deficiency is a rare metabolic disorder leading to cerebral
      infarctions, as seen in our five patients, and should be considered in the
      differential diagnosis of children who have had a stroke, particularly when
      associated with hypoglycemia and myopathy.

PMID- 8883662
TI  - Whipple disease confined to the central nervous system in childhood.
AB  - In a case of pediatric Whipple disease confined to the central nervous system,
      white matter lesions initially appeared as areas of very low signal intensity on
      T1-weighted MR images and as areas of hyperintensity on proton density-weighted
      and T2-weighted images, and showed slight peripheral enhancement on delayed
      contrast-enhanced T1-weighted images. On MR studies obtained 3 and 6 months after
      antibiotic therapy, the lesions had decreased in size and no longer enhanced.
      They became progressively less hypointense on T1-weighted images and less
      hyperintense on T2-weighted images.

PMID- 8883663
TI  - MR features of an intracerebellar chloroma.
AB  - Granulocytic sarcoma (chloroma) is a rare tumor almost always associated with
      leukemia. Intraaxial brain lesions are rare, and can mimic infection or primary
      neoplasm. This intracerebellar chloroma arose after autologous bone marrow
      transplantation in a 29-year-old woman with leukemia. On T1-weighted MR images,
      the lesion was isointense with gray matter, and enhanced homogeneously. On T2
      weighted and proton density-weighted MR sequences, the center was isointense with
      gray matter and the periphery was isointense with white matter. The lesion's
      tendency to remain isointense on sequences with long repetition times is
      presumably attributable to the presence of myeloperoxidase.

PMID- 8883664
TI  - MR of xanthogranuloma of the choroid plexus.
AB  - We present a case of a xanthogranuloma of the lateral ventricle choroid plexus in
      association with focal areas of abnormal T2 signal in the tegmentum of the pons
      as well as within the middle cerebellar peduncles. The characteristic MR
      appearance of this rare entity is described along with a pathologic basis
      suggesting an association with posterior fossa lesions.

PMID- 8883665
TI  - Cerebral schistosomiasis: MR and CT appearance.
AB  - After returning from Africa, a 54-year-old man began to have episodes of headache
      and nausea, then a cerebral convulsion. Clinical and laboratory findings and
      response to chemotherapy indicated the diagnosis of cerebral schistosomiasis.
      Three lesions were seen on CT and MR studies: two appeared to be subacute
      intracerebral hematomas, one in the right parietal lobe and one in the frontal
      lobe; the third lesion, in the cortex of the left occipital lobe, appeared to be
      a cyst. These lesions could represent small granulomatous tissue reactions with
      secondary hemorrhages.

PMID- 8883666
TI  - Factors predicting re-referral following crisis intervention for community-based
      persons with developmental disabilities and behavioral and psychiatric disorders.
AB  - Characteristics of 98 clients re-referred to receive services from a community
      based crisis intervention program were compared to those of program clients who
      were served during the same 5.25-year period who were not referred. The majority
      of re-referrals occurred because of the same challenging behavior causing initial
      referral. Eight-eight percent of re-referral clients received the additional
      referral by 2 years after initial discharge. For persons under 30, nonfamily
      residence and initial diagnosis of self-injurious behavior were the strongest
      predictors. For those over 30, the most important factor was aggression.
      Recidivism following crisis intervention appears to be a complex function of
      client characteristics and community capabilities.

PMID- 8883667
TI  - Dyskinetic movement disorder among adults with mental retardation: phenomenology
      and co-occurrence with stereotypy.
AB  - We screened for the occurrence of dyskinetic and stereotypic movement disorders
      using item-independent screening protocols to determine whether these forms of
      movement disorder can be distinguished among adults with mental retardation.
      Stereotypies and dyskinesias were reliably distinguished in terms of topography.
      Tardive dyskinesia occurred in 18.2% of a cohort of individuals receiving chronic
      neuroleptic treatment. Stereotypic movement disorder was associated with
      increased dyskinesia scores and increased prevalence of tardive dyskinesia.
      Increased dyskinesia scores were also found for subjects exhibiting stereotypy
      who had been free of neuroleptic treatment for 3 years. Results indicate that
      dyskinesia and stereotypy are discriminable movement disorders and provide
      preliminary support for the hypothesis that they may be related by common
      mechanisms.

PMID- 8883668
TI  - Evidence for visual imagery deficits in persons with mental retardation.
AB  - Performance on four mental imagery tasks by two groups of adolescents with mental
      retardation with different etiologies (sociocultural, organic) were compared to
      that of children without mental retardation who were of comparable or lower MAs.
      Findings reveal an important deficit in imagery abilities in both retarded
      groups; their performance was poorer compared to the children without mental
      retardation matched on MA. Subjects with mental retardation due to sociocultural
      retardation scored higher on some tasks than did those whose mental retardation
      was due to organic causes. This finding underscores the need to consider
      etiology. This marked deficit in imagery ability in persons with mental
      retardation may be the source of other difficulties they encounter in cognitive
      activities that involve this representational format.

PMID- 8883669
TI  - Influence of child diagnosis on family and parental functioning: Down syndrome
      versus other disabilities.
AB  - Although children with Down syndrome are popularly conceived of as having easy
      temperaments and agreeable personalities, conflicting reports exist as to whether
      they are easier to rear than are children with other developmental disabilities.
      To compensate for possibly biased samples in earlier studies, we employed three
      methodological strategies, including case-by-case matching of families raising
      children with Down syndrome and families raising children with other types of
      developmental disabilities. Results showed no differences between matched groups
      on various measures of functioning, a finding replicated with multiple regression
      techniques. However, in unmatched samples families of children with Down syndrome
      showed better functioning. Thus, previous research demonstrating better
      adjustment for families rearing children with Down syndrome should be re-examined
      for sampling biases.

PMID- 8883670
TI  - The labyrinth of IDEA: school decisions on referred students with subaverage
      general intelligence.
AB  - A sample of 150 children referred to Student Study Teams was assessed with a
      psychometric battery. Behavioral and academic ratings were obtained from
      teachers. Forty-three children scored at or below 75 on the WISC-III. We examined
      schools' subsequent classification decisions to ascertain how schools dealt with
      low-IQ students with academic and behavioral problems. Schools reached decisions
      regarding 35 of the children: Only 6 were classified as having mental
      retardation, and 18, as having learning disabilities. Findings were discussed in
      terms of (a) decline in identification rates of mild mental retardation and (b)
      the extent to which school decisions adhere to the research criteria.

PMID- 8883671
TI  - Causes of age-related decline in adaptive behavior of adults with Down syndrome:
      differential diagnoses of dementia.
AB  - Although a decline in adaptive behavior with age in adults with Down syndrome has
      been established, the underlying causes of the decline remain unresolved.
      Differential causes of the decline in 201 adults with Down syndrome were
      investigated. Aging, dementia, and severity of mental retardation were found to
      be significant factors. Absence of a medical illness was a factor that predicted
      a higher level of adaptive behavior. No significant difference in age-related
      maladaptive behaviors was found. However, a clinical diagnosis of dementia was a
      predictive factor for increased maladaptive behavior. Clinical implications of
      these findings were discussed.

PMID- 8883672
TI  - Relation between curricular activities and problem behaviors of students with
      mental retardation.
AB  - The correlations between students' problem and appropriate behaviors and
      characteristics of the curricular activities in which they were engaged was
      examined. Curricular activities were rated to determine whether they were
      socially functional, peer-referenced, and behaviorally functional. Students'
      behaviors and curricular activities in 64 classrooms were directly observed
      during the regular daily routine. Results showed a significant negative
      correlation between ratings of the characteristics of curricular activities and
      students' problem behaviors and a significant positive correlation between
      ratings of curricular activities and students' appropriate behaviors. The pattern
      of significant correlations was also reflected in individual subscale scores.
      Implications of these results for classroom practice and the remediation of
      problem behaviors were discussed.

PMID- 8883673
TI  - Food preferences among individuals with and without Prader-Willi syndrome.
AB  - Eleven individuals with Prader-Willi syndrome and 10 control subjects who had
      mental retardation due to other causes (with and without overeating histories)
      participated in two experiments on food preferences. They gave preference
      rankings for various foods, then chose between a small amount of their most
      preferred food and an alternative choice of a larger amount of mixed-preference
      foods (Experiment 1) or an alternative choice of a larger amount of their least
      preferred food (Experiment 2). Unlike overweight-prone control subjects who
      selected sweet food over a larger quantity of unpreferred food, subjects with
      Prader-Willi syndrome selected preferred items only over least-preferred items
      (Experiment 2) but not over mixed-preference items (Experiment 1). Implications
      for treatment were discussed.

PMID- 8883674
TI  - Kennedy Lecture. Unstable knees in unstable times.

PMID- 8883675
TI  - A muscle-splitting approach to the ulnar collateral ligament of the elbow.
      Neuroanatomy and operative technique.
AB  - The standard surgical approach for repair or reconstruction of the ulnar
      collateral ligament of the elbow involves lifting off of the tendon of the common
      flexor bundle at its origin on the medial epicondyle. However, a more limited
      muscle-splitting approach may be feasible. A muscle-splitting approach is less
      traumatic to the flexor-pronator muscle mass, and it could decrease operative
      time and lessen immediate morbidity after surgery. A proposed muscle-split
      through the common flexor bundle extends from the medial humeral epicondyle to a
      point distal to the tubercle of the ulna such that repair or reconstruction can
      be performed on the ulnar collateral ligament. To examine the feasibility of this
      approach, we performed a study combining anatomic dissections with clinical
      observations. We dissected 15 fresh-frozen adult cadaveric elbows to examine the
      neuroanatomy of the medial side of the elbow. All pertinent nerves were
      identified and mapped. From these data, we defined a "safe zone" for a muscle
      splitting approach to the ulnar collateral ligament that allows adequate room for
      repair or reconstruction of the ligament without risking denervation of the
      surrounding musculature. The safe zone extends from the medial humeral epicondyle
      to approximately 1 cm distal to the insertion of the ulnar collateral ligament on
      the tubercle of the ulna. Twenty-two patients with ulnar collateral ligament
      tears underwent either a direct repair or a reconstruction of the ligament using
      the proposed muscle-splitting approach. With a minimum followup of 1 year, there
      was no clinical evidence of muscle denervation. From the combined anatomic study
      and clinical data, we believe that a less traumatic muscle-splitting approach to
      the ulnar collateral ligament affords a safe and simple surgical approach for
      repair or reconstruction of the ligament.

PMID- 8883676
TI  - The manual muscle examination for rotator cuff strength. An electromyographic
      investigation.
AB  - The electromyographic activity of eight muscles of the rotator cuff and shoulder
      girdle (supraspinatus, infraspinatus, subscapularis, pectoralis, latissimus
      dorsi, and the anterior, middle, and posterior deltoid) was measured from the
      nondominant shoulders of 11 subjects during a series of 29 isometric
      contractions. The contractions simulated different positions used for strength
      testing of the rotator cuff and involved elevation, external rotation, and
      internal rotation at three degrees of initial humeral rotation (-45 degrees of
      internal rotation, 0 degree, +45 degrees of external rotation) and scapular
      elevation (0 degree, 45 degrees, 90 degrees). Isolation of the supraspinatus
      muscle was best achieved with the test position of elevation at 90 degrees of
      scapular elevation and +45 degrees (external rotation) of humeral rotation.
      Isolation of the infraspinatus muscle was best achieved with external rotation at
      0 degree of scapular elevation and -45 degrees (internal rotation) of humeral
      rotation. Isolation of the subscapularis muscle was best achieved with the Gerber
      push-off test. This study used four criteria for identifying the optimal manual
      muscle test for each rotator cuff muscle: 1) maximal activation of the cuff
      muscle, 2) minimal contribution from involved shoulder synergists, 3) minimal
      provocation of pain, and 4) good test-retest reliability. Based on the results of
      this study and known painful arcs of motion, an objective identification of the
      optimal tests for the manual muscle testing of the cuff was elucidated.

PMID- 8883677
TI  - Validation of the lift-off test and analysis of subscapularis activity during
      maximal internal rotation.
AB  - We used electromyographic analysis to determine the muscle activity of the
      shoulder muscles during the lift-off test and during resisted internal rotation.
      The activity in the upper and lower subscapularis muscle during a lift-off test
      from the region of the midlumbar spine was approximately 70% of maximal voluntary
      contraction. This level was significantly higher than for all the other muscles
      tested (P < 0.05). The lift-off test with the hand placed in the region of the
      midlumbar spine resulted in one-third more electromyographic activity in the
      subscapularis muscle than when the test was modified and performed with the hand
      at the buttocks region. A resisted lift-off test resulted in higher activities in
      all the muscles, but only a small increase in the pectoralis major muscle. The
      pectoralis major muscle was significantly more active during resisted internal
      rotation with the arm in front of the body. Comparison of activity in the upper
      subscapularis with that in the lower subscapularis muscle showed no significant
      differences during any of the tests. This study documents the importance of the
      subscapularis muscle during the lift-off test and suggests that other potential
      internal rotators of the humerus have a limited role in maintaining internal
      rotation when the arm is placed behind the back.

PMID- 8883678
TI  - Development of a distance-based interval throwing program for Little League-aged
      athletes.
AB  - We developed a distance-based interval throwing program for Little League-aged
      athletes (9 to 12 years) to be used in training and rehabilitation. The timing
      and repetition parameters were developed from data collected during 400 innings
      of organized baseball during a single season, and short toss distance from Little
      League rules for field dimensions. There were 1022 boys from organized baseball
      teams in the four studies. Maximal distance and speed measurements were recorded
      for 853 boys. We developed a mathematical model from these data to predict
      maximal throwing distance from maximal throwing speed. This model was then tested
      on a second sample of 114 players. We compared the predicted distance with the
      actual maximal throwing distance; the correlation coefficient was 0.92. Forty
      players aged 9 to 12 participated in a study to assess degradation of speed and
      distance. The average variability of the speed was small (< 5 mph), but the
      variability in distance was large (22.4 feet). Fifteen boys then threw the entire
      throwing program as designed. These results show that healthy young athletes can
      be expected to be able to throw the predicted value of this practical progressive
      interval throwing program for Little League-aged athletes. The appropriate
      program can be assigned from age and known preinjury pitch speed.

PMID- 8883679
TI  - Anterior knee laxity and loss of extension after anterior cruciate ligament
      injury.
AB  - This study was performed to examine the relationship between knee extension loss
      and the length of time after injury. We also wanted to compare anterior laxity in
      anterior cruciate ligament-injured knees in the early and late stages of injury.
      Loss of knee extension was measured in 81 patients with anterior cruciate
      ligament injury using lateral radiography with the injured leg relaxed and
      elevated. Extension loss was defined as the difference in maximal extension angle
      between the injured and uninjured knees. Average loss of extension was 3.6
      degrees in the 17 knees in which the anterior cruciate ligament had been torn 3
      weeks or less before examination (the acute injury group) and 0.6 degree in the
      64 knees in which the anterior cruciate ligament had been torn more than 3 weeks
      before examination (the chronic injury group). The extension loss in the acutely
      injured knees was significantly greater compared with that in the uninjured knees
      and in the chronically injured knees. Arthrometric measurements using the KT-1000
      arthrometer were reliable to diagnose an acute tear. There was no correlation
      between the degree of extension loss and arthrometric anterior knee laxity
      measurements. In 12 patients, the initial extension deficit in the early stage of
      injury significantly resolved with time, and manual maximum arthrometric
      measurements of anterior knee laxity improved spontaneously with time.

PMID- 8883680
TI  - The effect of anterior cruciate ligament graft elongation at the time of
      implantation on the biomechanical behavior of the graft and knee.
AB  - This investigation determined the effect that anterior cruciate ligament graft
      elongation at the time of surgical reconstruction has on the long-term
      biomechanical behavior of the graft and knee joint. We chose the canine model for
      anterior cruciate ligament reconstruction, using the medial third of the patellar
      tendon with attached proximal bone block. Elongation of the graft was measured
      immediately after graft fixation during passive knee flexion using the Hall
      effect transducer. The dogs were divided into either Group 1 (graft elongation
      behavior within the 95% confidence limits of the normal anterior cruciate
      ligament) or Group 2 (graft elongation behavior more than the 95% confidence
      limits of the normal anterior cruciate ligament). All of the dogs were sacrificed
      18 months postoperatively, and we evaluated anteroposterior load displacement
      (i.e., anteroposterior laxity) of the knee and the structural properties of the
      graft. The anteroposterior laxity behavior of the reconstructed knees in Group 2
      was significantly more than that of Group 1. Group 2 had significantly less
      linear stiffness of the graft than Group 1. There was no difference in the
      ultimate failure load and absorbed energy at failure values of the grafts between
      Groups 1 and 2. The findings from this investigation indicate that the graft
      elongation behavior at the time of reconstruction is a critical factor that
      influences the long-term success of anterior cruciate ligament reconstruction.

PMID- 8883681
TI  - The effects of muscle fatigue on neuromuscular function and anterior tibial
      translation in healthy knees.
AB  - We investigated the effect of quadriceps and hamstring muscle fatigue on anterior
      tibial translation and muscle reaction time in 10 healthy subjects. The six men
      and four women had an average age of 21.3 years and had no known pathologic knee
      conditions. Each patient underwent a knee examination, arthrometer measurements
      of tibial translation, subjective functional assessment, and an anterior tibial
      translation stress test before and after quadriceps and hamstring muscle
      fatiguing exercise. The recruitment order of the lower extremity muscles in
      response to anterior tibial translation did not change with muscle fatigue.
      However, the results showed an average increase of 32.5% in anterior tibial
      translation (range, 11.4% to 85.2%) after fatigue. Muscle responses in the
      gastrocnemius, hamstring, and quadriceps originating at the spinal cord and
      cortical level showed significant slowing and, in some cases, an absence of
      activity after the quadriceps and hamstring muscles were fatigued. The increases
      in displacement after fatigue strongly correlated (0.62 to 0.96) with a delay in
      cortical-level activity (intermediate and voluntary). Muscle fatigue, which
      appears to affect the dynamic stability of the knee, alters the neuromuscular
      response to anterior tibial translation. Therefore, fatigue may play an important
      role in the pathomechanics of knee injuries in physically demanding sports.

PMID- 8883682
TI  - Biomechanical responses to repeated stretches in human hamstring muscle in vivo.
AB  - To examine stiffness, energy, and passive torque in the dynamic and static phases
      of a stretch maneuver in the human hamstring muscle in vivo we used a test-retest
      protocol and a repeated stretches protocol. Resistance to stretch was defined as
      passive torque (in newton-meters) offered by the hamstring muscle group during
      passive knee extension as measured using an isokinetic dynamometer with a
      modified thigh pad. In 13 uninjured subjects, the knee was passively extended to
      a predetermined final position (0.0875 rad/ sec, dynamic phase) where it remained
      stationary for 90 seconds (static phase). The test-retest protocol included two
      tests administered 1 hour apart. On a separate occasion, five consecutive static
      stretches were administered separated by 30 seconds and followed by a sixth
      stretch 1 hour later. For the test-retest phase, stiffness and energy in the
      dynamic phase and passive torque in the static phase did not differ and yielded
      correlations of r = 0.91 to 0.99. During the static phase, passive torque
      declined in both tests (P < 0.0001). For the repeated stretches, decreases were
      observed for energy (P < 0.01) and stiffness (P < 0.05) in the dynamic phase and
      for passive torque (P < 0.0001) in the static phase. However, the decline in the
      variables returned to baseline within 1 hour. The data show that the method
      employed is a useful tool for measuring biomechanical variables during a stretch
      maneuver. This may provide a more detailed method to examine skeletal muscle
      flexibility.

PMID- 8883683
TI  - The use of cold therapy after anterior cruciate ligament reconstruction. A
      prospective, randomized study and literature review.
AB  - We performed a randomized, prospective study to assess the effectiveness of
      postoperative cold therapy in patients who had anterior cruciate ligament
      reconstructions. Drain output, length of hospital stay, range of motion, and use
      of pain medication were all assessed. Patients were randomized into one of four
      groups after surgery. Group 1 patients had a cooling pad applied to the knee
      postoperatively and set at a temperature of 40 degrees to 50 degrees F, Group 2
      had the cooling pad set at 70 degrees to 80 degrees F, Group 3 received ice
      packs, and Group 4 received no cold therapy of any kind. The skin temperatures in
      Groups 1 and 3 were significantly lower than the skin temperatures in Groups 2
      and 4 (P < 0.001). The length of hospital stay, range of motion at discharge, use
      of oral and intramuscular pain medicine, and drain output were not significantly
      different between groups. No complications related to the type of cold therapy
      were seen in any group. Thus, both ice packs and cooling pads significantly
      decreased knee temperature, but we found no objective benefits in the early
      postoperative course due to this decrease in temperature.

PMID- 8883684
TI  - Chondral delamination of the knee in soccer players.
AB  - This study reports on the diagnosis and treatment of chondral delamination in the
      knees of soccer players. The authors attempted to provide a clinical standard for
      comparison with emerging cartilage repair techniques. Twenty-three consecutive
      chondral fractures in a homogeneous population of athletes were evaluated using
      physical examination, magnetic resonance imaging, and arthroscopic examination.
      All knees were treated with debridement to a stable border and removal of the
      calcified cartilage base. Results were graded using the scoring system advocated
      by proponents of chondral transplant. All patients reported pain that limited
      soccer activities. Effusions occurred in 48%, joint line tenderness in 33%, and
      crepitus in 19% of the knees. Results from magnetic resonance imaging correlated
      with arthroscopic examination in 21% of the knees. Arthroscopic examinations
      revealed lesions on the medial femoral condyle in eight patients, the patella in
      six, the lateral femoral condyle in six, and the trochlea in three. Athletes
      returned to play at an average of 10.8 weeks. Repeat arthroscopic procedures in
      eight cases revealed fibrocartilage at the initial site. There were 6 excellent,
      9 good, 0 fair, and 0 poor results at their 1-year followup examinations (15
      knees). The definitive diagnosis of chondral delamination relies on a thorough
      arthroscopic probing of the articular surface. The early functional results of
      this treatment compare favorably with the autologous transplantation technique.
      Caution, however, is recommended when treating articular cartilage injuries
      because no long-term data exists on whether any treatment modality can prevent
      the development of degenerative joint disease.

PMID- 8883685
TI  - The effect of nonablative laser energy on joint capsular properties. An in vitro
      histologic and biochemical study using a rabbit model.
AB  - The purpose of this study was to evaluate the effect of laser energy at
      nonablative levels on joint capsular histologic and biochemical properties in an
      in vitro rabbit model. The medial and lateral portions of the femoropatellar
      joint capsule from both stifles of 12 mature New Zealand White rabbits were used.
      Specimens were divided into three treatment groups (5 watts, 10 watts, and 15
      watt) and one control group using a randomized block design. Specimens were
      placed in a 37 degrees bath of lactated Ringer's solution and laser energy was
      applied using a holmium:yttrium-aluminum-garnet laser in four transverse passes
      across the tissue at a velocity of 2 mm/sec with the handpiece set 1.5 mm from
      the synovial surface. Histologic analysis revealed thermal alteration of collagen
      (fusion) and fibroblasts (pyknosis) at all energy densities, with higher laser
      energy causing significantly greater morphologic changes over a larger area (P <
      0.05). Application of laser energy did not significantly alter the biochemical
      parameters evaluated, including type I collagen content and nonreducible
      crosslinks (P > 0.05). This study demonstrated that nonablative laser energy
      caused significant thermal damage to the joint capsular tissue in an energy
      dependent fashion, but type I collagen content and nonreducible crosslinks (P >
      0.05). This study demonstrated that nonablative laser energy caused significant
      thermal damage to the joint capsular tissue in an energy-dependent fashion, but
      type I Collagen content and nonreducible corsslinks were not significantly
      altered.

PMID- 8883686
TI  - Chronic, painful ankle instability in skeletally immature athletes. Ununited
      osteochondral fractures of the distal fibula.
AB  - We report 10 cases of chronic, painful ankle instability in skeletally immature
      athletes associated with ununited osteochondral fragments of the distal fibula.
      All the patients experienced multiple inversion injuries with recurrent pain and
      instability that failed to improve after a supervised exercise and rehabilitation
      program. Osteochondral fragments of the distal fibula were visible on all
      standard radiographs of the affected ankles. Treatment consisted of operative
      excision of the bony fragment and an anatomic nonaugmented repair of the lateral
      ligament complex and capsule. All 10 patients were available for long-term
      followup an average of 6.5 years (+/-2) after surgery; all ankles improved
      functionally, with no recurrences of instability.

PMID- 8883687
TI  - Traumatic peroneal tendon instability.
AB  - To investigate the causes of, pathologic changes associated with, and treatment
      results after traumatic peroneal tendon subluxation or dislocation, we reviewed
      11 cases in 10 patients at a mean followup of 29 months. We also describe a
      technique of superior peroneal retinacular repair combined with fibular
      rotational osteotomy. Excellent clinical and functional results were achieved in
      9 of the 11 cases, enabling the patients to return to previous competitive sports
      by 3 months. There was one persisting subluxation that required further surgery.
      Another ankle, with chronic sepsis from previous surgery and documented
      degeneration of the ankle joint, had a recurrence of the infection and
      sequestration of the osteotomized fragment. The personal tendons, however,
      remained stabilized by the resultant scar tissue. We conclude that superior
      peroneal retinacular repair, with or without fibular rotational osteotomy, is a
      successful technique in treating both acute and recurrent instability of the
      peroneal tendons. It can be combined with a Brostrom repair when there is
      concurrent peroneal tendon and anterolateral ankle instability. Peroneal
      tenosynovitis and tendon splitting were commonly found at operation, especially
      in cases of recurrent instability. The degree of pathologic change in the tendon
      did not affect the clinical result.

PMID- 8883688
TI  - A one-year prospective study on back pain among novice golfers.
AB  - We conducted a 1-year follow-up study on back pain among 196 men taking up golf.
      A questionnaire on individual characteristics, occupation, sports, and back pain
      was distributed at the start of the study and was followed by another
      questionnaire after 12 months. Eleven percent of the original subjects (25 of
      211) were lost to followup, but withdrawal from the survey was not associated
      with health status. In the baseline survey (N = 221), the self-reported lifetime
      cumulative incidence of back pain was 63%; 28% reported back pain during the
      month before answering the questionnaire, and 13% reported current back pain.
      Athletes had an increased odds ratio of 2.1 (95% confidence interval, 1.1 to 4.0)
      for previous back pain. During the 12 months between the surveys, the incidence
      of first-time back pain was 8% and the incidence of recurrent back pain was about
      45%. Men involved in golf and another sport demonstrated a risk of 1.4 for
      recurrence of back pain, compared with men playing golf only. Six subjects
      attributed the recurrent back pain to playing golf. Given the high proportion of
      athletes in this study (68%), the risk factor of playing golf failed to
      demonstrate an additional significant effect on the general relationship between
      sport and back pain.

PMID- 8883689
TI  - Shoulder injuries during alpine skiing.
AB  - We retrospectively reviewed alpine skiing injuries at a destination ski resort
      during three seasons to characterize the incidence and types of shoulder
      injuries. A total of 3451 injuries in 3247 patients were reviewed. The overall
      injury rate was 4.44 injuries per 1000 skier-days. Injuries to the upper
      extremity represented 29.1% (N = 1004) of all alpine ski injuries. Injuries
      involving the shoulder complex (393 injuries in 350 patients) accounted for 39.1%
      of upper extremity injuries and 11.4% of all alpine skiing injuries. The rate of
      shoulder injury was 0.51 injuries per 1000 skier-days. Patients with shoulder
      injuries had a mean age of 35.4 years, and the male-to-female ratio of these
      patients was 3:1. Falls represented the most common mechanism of shoulder injury
      (93.9%) in addition to collisions with skiers (2.8%), pole planning (2.3%), and
      collisions with trees (1%). The most common shoulder injuries were rotator cuff
      strains (24.2%), anterior glenohumeral dislocations or subluxations (21.6%),
      acromioclavicular separations (19.6%), and clavicle fractures (10.9%). Less
      common shoulder injuries included greater tuberosity fractures (6.9%), trapezius
      muscle strains (6.4%), proximal humeral fractures (3.3%), biceps tendon strains
      (2.3%), glenoid fractures (1.5%), scapular fractures (1%), humeral head fractures
      (1%), sternoclavicular separations (0.5%), an acromial fracture (0.3%), a
      posterior glenohumeral dislocation (0.3%), and a biceps tendon dislocation
      (0.3%).

PMID- 8883690
TI  - The frequency of Baker's cysts associated with meniscal tears.
AB  - We reviewed the films of 1760 patients who had magnetic resonance image scanning
      of the knee joint to assess the most common pathologic changes associated with an
      incidental finding of a Baker's cyst. Of the 1760 knees scanned, Baker's cysts
      were noted in 238. The cysts were classified as small (55%), medium (30%), or
      large (15%) and were primarily found on the medial side of the knee (94%). The
      menisci were evaluated and changes were classified as complete tears, where
      signal contacts the surface, or degenerative intrasubstance tears. One hundred
      eleven (47%) complete meniscal tears were found, and 88 (37%) degenerative tears.
      The majority of tears were found in the posterior horn of the medial meniscus (65
      complete tears and 45 degenerative tears). Thus, 199 tears were found in 170
      knees, and 106 of the 170 knees (62%) had tears of the posterior horn of the
      medial meniscus. Baker's cysts are frequent findings on physical examinations and
      on magnetic resonance imaging scans of the knee. They are thought to be due to
      intraarticular pathologic changes, usually posterior meniscal tears. This study
      documents the association between Baker's cysts and meniscal tears and notes that
      a complete tear is not necessary for the cyst to be present.

PMID- 8883691
TI  - Assessment of thumb positioning in the treatment of ulnar collateral ligament
      injuries. A laboratory study.
AB  - In the treatment of ulnar collateral ligament injuries in the metacarpophalangeal
      joint of the thumb, a cast or splint is often molded with the thumb and hand
      positioned so the patient can return quickly to a particular sport or activity.
      However, it is unknown whether a given position of immobilization or whether an
      early rehabilitation program will compromise ligament healing by causing undue
      tension in the ligament. To better define acceptable positions for thumb
      immobilization and a safe range of motion, this laboratory study measured strain
      in the ulnar collateral ligament at different degrees of metacarpophalangeal
      joint flexion. Ligament strain was found to increase with increasing joint
      flexion; the most significant increases in strain occurred as the joint moved
      from 0 degree to 25 degrees of flexion, with the dorsal portion of the ligament
      demonstrating greater strain than the palmar portion. Based on these results,
      immobilization of the metacarpophalangeal joint in excessive flexion and
      unrestricted early rehabilitation exercises should be done with caution and
      guided by the grade of injury or the quality of repair.

PMID- 8883692
TI  - Knee joint dynamics predict patellar tendinitis in elite volleyball players.
AB  - We quantified the lower extremity dynamics developed during the volleyball spike
      and block jumps to find out if predictive relations exist between jump dynamics
      and patellar tendinitis. Lower extremity movement biomechanics were analyzed for
      10 members of the 1994 Canadian Men's National Volleyball Team (all right-handed
      hitters). Based on physical examination, 3 of the 10 players had patellar tendon
      pain associated with patellar tendinitis at the time of testing. In masked
      biomechanical and logistic regression analyses, we discovered that the vertical
      ground-reaction force during the take-off phase of both spike and block jumps was
      a significant predictor of patellar tendinitis-correctly predicting the presence
      or absence of patellar tendinitis in 8 of 10 players. Deepest knee flexion angle
      (during landing from the spike jump) predicted 10 of 10 cases correctly for the
      left knee. The external tibial torsional moment (during the takeoff for the right
      knee with the spike jump and for the left knee with the block jump) was also a
      significant predictor of tendinitis. In these players, the likelihood of patellar
      tendon pain was significantly related to high forces and rates of loading in the
      knee extensor mechanism, combined with large external tibial torsional moments
      and deep knee flexion angles.

PMID- 8883693
TI  - Incidence of injury in Texas girls' high school basketball.
AB  - We studied the incidence of injury in girl's varsity basketball to characterize
      injury demographics in high school athletics. We defined a reportable injury as
      one that occurred during organized practice or competition, resulted in either
      missed practice or game time, required physician consultation, or involved the
      head or face. We prospectively evaluated the athletes on team rosters during the
      1993 to 1994 season from 100 randomly selected Class 4A and 5A Texas public high
      schools that employed full-time certified athletic trainers. The 890 student
      athletes from 80 schools ranged in age from 14 to 18 years. Four hundred thirty
      six injuries were reported for a rate of 0.49 per athlete per season. Injury
      risk, calculated on the basis of exposure time, was 0.4% per hour per athlete.
      Although game time accounted for only 12.5% of exposure time, it represented one
      half of the total injuries. Sprains and strains (56%) were the most common
      injuries, followed by contusions (15%) and dental injuries (14%). Injuries to the
      ankle (31%) and knee (19%) were by far the most common. There were 34 severe
      injuries defined as requiring surgery or hospitalization, for a rate of 0.038 per
      athlete per season. Knee injuries were by far the most likely to require
      surgeries, and ACL injuries accounted for 69% of the severe knee injuries.

PMID- 8883694
TI  - Intramedullary nailing for chronic tibial stress fractures. A review of five
      cases.
AB  - Chronic tibial stress fracture is an unusual condition that is primarily seen in
      athletes and military personnel. Recurrent or recalcitrant stress fractures can
      be career-ending because they require lengthy nonoperative treatment. We
      performed a retrospective review of five patients who underwent intramedullary
      tibial nailing for recalcitrant stress fractures at Womack Army Medical Center,
      Ft. Bragg, North Carolina, from 1991 to 1994. Interviews were used to survey the
      patient's history and outcome. We reviewed each case regarding preoperative
      symptoms, preoperative treatment, surgery performed, radiographic findings, and
      functional outcome. In each case there were several similarities in symptoms and,
      most notably, radiographic findings and failure of nonoperative therapy for more
      than 1 year. Each patient had an unusually narrow medullary canal, a thickened
      anterior cortex, and a linear unicortical fracture line on the anterior or
      tension side. Although functional results varied, all patients reported
      improvement in their symptoms and could return to limited running. There were two
      excellent results (defined as unlimited pain-free running and resolved tibial
      pain) and three good results. We believe intramedullary tibial nailing should be
      considered for treating chronic stress fractures of the midanterior tibia that
      are recalcitrant to nonoperative therapy in a selected group of patients.

PMID- 8883695
TI  - Clinical failure of tibial interference screw fixation after anterior cruciate
      ligament reconstruction. A report of two cases.

PMID- 8883696
TI  - Late patellar tendon ruptures after removal of the central third for anterior
      cruciate ligament reconstruction. A report of two cases.
AB  - Patellar tendon rupture after removal of the central third for ACL reconstruction
      is a rare complication. Only nine cases have been previously reported, and all of
      these occurred within the first 10 months after surgery. We report two cases of
      late patellar tendon ruptures occurring at more than 3 and 6 years, respectively,
      after surgery. A review of the literature has suggested but not conclusively
      supported that devascularization, an alteration in tendon healing and remodeling,
      or injury to the remaining tendon at the time of graft harvest may be possible
      causes of this rare complication. Biopsy tissue from any future patellar tendon
      ruptures after removal of its central third could contribute to a better
      understanding of this anomaly.

PMID- 8883697
TI  - A statistics primer. Hypothesis testing.

PMID- 8883698
TI  - Acute and chronic brain injury in United States National Team Soccer Players.

PMID- 8883699
TI  - Soft tissue for allograft reconstruction of the human knee: a survey of the
      American Association of Tissue Banks.

PMID- 8883700
TI  - Football cleat design and its effect on anterior cruciate ligament injuries.

PMID- 8883701
TI  - Interventional brain SPECT--a review.
AB  - Brain SPECT with HMPAO or ECD has-due to its short accumulation period--a rather
      high time resolution of approx 60 sec. Compared to isopropyl amphetamine (I-123)
      and FDG-PET, shortlasting interventions may be evaluated by SPECT. Usually, a two
      step approach is used, injecting one third of the dose under baseline conditions
      and two thirds during intervention. The first study is then subtracted from the
      second study, resulting in a "difference" image which allows to calculate the
      effect of the intervention. These interventional procedures may include drug,
      mechanical, and mental intervention as well as ictal, blood pressure and receptor
      intervention. Moreover, the difference of pCO2 after hyperventilation or
      hypoventilation may also be used as a stimulus. The above mentioned procedures
      are described in detail.

PMID- 8883702
TI  - Accumulation of 99mTc-MIBI in bone marrow.
AB  - 99mTc-MIBI (Sestamibi) was originally developed for myocardial perfusion studies.
      The agent also may be used for the depiction and characterization of tumors.
      Performing such examinations has shown uptake in skeletal structures in several
      patients suggesting bone engagement of the disease which later was excluded.
      Retrospective evaluation of 44 examinations with 99mTc-MIBI performed in order to
      localize diseased parathyroid in patients with suspected hyperparathyroidism
      showed skeletal activity in 21 (48%) patients. Although these patients represent
      a selected group, the observation indicates a mechanism for skeletal accumulation
      of this radiopharmaceutical. Evaluation of another 13 normocalcemic patients
      undergoing whole-body registration for malignancy staging or to assess lower
      extremity ischemia with 99mTc-MIBI showed skeletal activity in 6 (46%) patients.
      Complementary mouse experiments confirmed skeletal uptake of 99mTc-MIBI, where
      most of the activity is taken up by the red bone marrow. It is concluded that
      homogeneous, diffuse weak skeletal activity at examination with 99mTc-MIBI is a
      normal finding and does not indicate malignancy.

PMID- 8883703
TI  - Evaluation of four radiopharmaceuticals for imaging inflammation in a rabbit
      model of arthritis.
AB  - We compared the utility of four radiopharmaceuticals; 111In-chloride, 67Ga
      citrate, 111In labeled leukocytes (WBCs) and 99mTc-MDP for assessing the
      inflammatory response in antigen induced arthritis in a rabbit model. A total of
      20 rabbits, divided into four equal groups, were included in this study. Each
      group was studied twice with a single radiotracer; a baseline study and a follow
      up study after induction of the arthritis. Knee to knee, knee to whole body, and
      knee to liver (except for the group studied with 99mTc-MDP) ratios were
      generated. Knee to knee ratios showed no significant change from baseline to
      arthritis studies in any of the four groups. Significantly increased knee to
      total body ratios were seen in all of the groups, except for the group studied
      with 99mTc-MDP. The greatest increase was seen in the group studied with 111In
      chloride. Significantly increased knee to liver ratios were observed in all three
      groups for which these ratios were generated and again the greatest increase was
      observed in the group studied with 111In-chloride. In summary, based on the
      higher uptake observed in this group, of the four radiotracers evaluated, 111In
      chloride is probably the most useful for monitoring the inflammatory response in
      antigen induced arthritis. The symmetry of the response suggests that it may also
      be useful in monitoring the response to therapy.

PMID- 8883704
TI  - Cerebral blood flow and vascular response to hypercapnia in hypertensive patients
      with leukoaraiosis.
AB  - Both arteriosclerosis and leukoaraiosis have a close relationship with
      hypertension, but the relationship between cerebral hemodynamics and
      leukoaraiosis in hypertensive patients has not been fully examined. To clarify
      this issue, we measured the regional cerebral blood flow (rCBF) and
      cerebrovascular response to hypercapnia in hypertensive patients with various
      degrees of leukoaraiosis. The subjects consisted of 7 normotensive normal
      controls and 17 hypertensive patients. The hypertensive patients were divided
      into three groups according to the severity of white matter lesions
      (leukoaraiosis) on MRI and the presence of dementia, namely, (1) negative or mild
      leukoaraiosis without dementia, (2) moderate to severe leukoaraiosis without
      dementia and (3) severe leukoaraiosis with dementia. Both the rCBF and the
      cerebrovascular response to hypercapnia were measured by the O-15 H2O bolus
      injection method and positron emission tomography. The rCBF in hypertensive
      patients without dementia did not decrease when compared with the normotensive
      controls, but the rCBF in hypertensive patients with dementia markedly decreased
      in the cerebral cortices and white matter. On the other hand, the cerebrovascular
      response to hypercapnia declined with the severity of leukoaraiosis, and it
      decreased most severely in patients with severe leukoaraiosis and dementia. Our
      results indicate that the reduction in the cerebral hemodynamic reserve capacity
      has a close relationship with the severity of leukoaraiosis in hypertensive
      patients, although the rCBF is maintained in hypertensive patients without
      dementia, and suggest that arteriosclerotic change reduces cerebrovascular CO2
      response and causes a leukoaraiosis in hypertensive patients.

PMID- 8883705
TI  - A new decision rule for parameter delta in MAP EM (OSL) reconstruction with the
      Gibbs prior.
AB  - In MAP EM (OSL) reconstruction with the Gibbs prior, the parameter delta which
      appears in the prior is commonly treated as a fixed value. Because the quality of
      reconstructed images depends on this parameter, we have to select delta very
      carefully, and because the statistics of an image vary locally, we should not
      choose a single delta value for each image. We propose a new decision rule to
      select an appropriate local delta. In our proposed method, delta is determined as
      the median of the differences between a value of the pixel of interest and those
      of neighboring pixels. This selection yields an appropriate prior depending on
      the regional statistics. The prior therefore preserves the edge property without
      amplifying statistical noise and it is not necessary to know the appropriate
      delta value to obtain high quality images. We performed computer simulations to
      determine the effectiveness of the proposed method. The results showed that the
      quality of reconstructed images obtained with the proposed method was superior to
      those obtained with the prior with a fixed delta.

PMID- 8883706
TI  - Comparative study of 201Tl-scintigraphic image and myocardial pathologic findings
      in patients with dilated cardiomyopathy.
AB  - The objective of the present study was to characterize the production of 201Tl
      myocardial perfusion defects, the relation between the 201Tl multiple small
      defects and the myocardial damage indicated by myocardial fibrosis shown
      histopathologically in patients with dilated cardiomyopathy (DCM). Rest 201Tl
      scintigraphy was performed in thirty-seven patients with myocardial tissue
      fibrosis by endomyocardial biopsy, and without stenosis of the coronary artery.
      201Tl myocardial SPECT images were visually classified into 4 grades according to
      the severity of inhomogeneous perfusion defects (IPD), 0: none, 1: slight, 2:
      moderate, 3: severe. 201Tl uptake, defect regions (DR), and coefficient of
      variation % (CV%) were also quantified by Bull's eye quantification in nineteen
      patients. During cardiac catheterization, three biopsy specimens were obtained
      from the lateral wall to the apical region of the left ventricle and the amount
      of fibrosis was assessed by means of light microscopic morphometry. The
      myocardial fibrosis was also classified into 4 grades by a point-counting method.
      Autopsy study was also assessed in six patients. 201Tl perfusion defects were
      observed in 35 (94.6%) patients, of whom 29 (78.4%) showed inhomogeneous
      perfusion defects. Twenty-four (64.9%) showed Stage 0 and 201Tl findings, and 21
      (62.2%) had myocardial fibrosis in stage 1. Clinically, the correlation between
      the grades of the IPD, % 201Tl uptake, DR and CV% of myocardial uptake, which
      were calculated semiquantitatively by Bull's eye image, and the histological
      grades of fibrosis were also good (IPD vs. fibrosis: r = 0.7014; % 201Tl uptake
      vs. fibrosis: r = -0.6542; DR vs. fibrosis: r = 0.7027; CV% vs. fibrosis: r =
      0.6985). The 201Tl SPECT findings were in close agreement with the severity of
      myocardial fibrosis confirmed by autopsy, but the grading of the IPD was not
      related to the ejection fraction or left ventricular diameter. It showed a higher
      rate of inhomogeneous 201Tl myocardial perfusion defects (78.4%) in patients with
      DCM. This result may contribute to the clinical evaluation of DCM or
      differentiation from other diseases. Furthermore, the grading of 201Tl
      inhomogeneous perfusion defects related to the myocardial fibrosis of left
      ventricular myocardium may contribute to speculation of the myocardial
      degenerative stage in clinical settings.

PMID- 8883707
TI  - 123I-MIBG myocardial imaging in hypertensive patients: abnormality progresses
      with left ventricular hypertrophy.
AB  - Twenty-seven patients with essential hypertension were prospectively studied with
      123I-labeled metaiodobenzyl-guanidine (123I-MIBG) to assess the presence and
      location of impaired sympathetic innervation in hypertrophied myocardium.
      Thirteen patients had left ventricular hypertrophy on echocardiography, and 14
      had normal echocardiograms. The wash out ratio of 123I-MIBG in these two groups
      did not differ significantly (35.3 +/- 6.1 and 35.4 +/- 5.1) but was higher than
      in control subjects (29.4 +/- 6.7). The delayed heart-to-mediastinum count ratio
      was lower in the patients with hypertrophy than in the patients without
      hypertrophy (1.93 +/- 0.28 and 2.22 +/- 0.21; p < 0.05) and the control subjects
      (1.93 +/- 0.28 and 2.33 +/- 0.25; p < 0.05). On SPECT imaging, abnormalities in
      segmental uptake were frequent at the posterior and postero-lateral wall in both
      groups, although the hypertrophic group had more significant impairment. Our
      results lead to the hypothesis that hypertension in more advanced stages may be
      associated not only with hypertrophic changes but also with more advanced
      regional impairment of cardiac sympathetic innervation.

PMID- 8883708
TI  - Simple method to quantify myocardial glucose metabolism from MB ratio in
      myocardial FDG PET.
AB  - To provide a simple means of quantifying myocardial glucose metabolism, we tried
      to estimate the K complex (KC) from the myocardium to background ratio (MB
      ratio), which was obtained with a single static FDG scan and single venous
      sampling. In 48 fasting subjects and 74 subjects under oral glucose loading or
      insulin clamp, the reference KC was obtained from Patlak analysis by using an
      input function. We compared the reference KC with the MB ratio at 35 min 45 sec,
      45 min 45 sec, and 55 min 45 sec, and with the FDG uptake index (FUI) reported by
      Tamaki. The correlation between KC and each index was very close during fasting
      (r = 0.97, 0.98, 0.98 and 0.97, respectively n = 48), and clinically acceptable
      during oral glucose loading and insulin clamp (r = 0.92, 0.91, 0.90 and 0.93,
      respectively n = 74). The average differences between the reference KC and KC
      estimated from the simple method were 13%, 10%, 8%, and 13%, respectively, during
      fasting, and 15%, 14%, and 16%, respectively, during oral glucose loading and
      insulin clamp. Both the MB ratio and FDG uptake index can be used for the simple
      estimation of myocardial glucose metabolism not only during fasting but also
      during oral glucose loading and insulin clamp, although the MB ratios at 45 min
      and at 55 min were slightly better than MB that at 35 min and the FDG uptake
      index during fasting.

PMID- 8883709
TI  - Ectopic accumulation of 99mTc-HMDP in primary lung cancer in comparison with CT
      findings.
AB  - The purpose of this study was to evaluate the frequency and the extent of
      extraosseous 99mTc-HMDP accumulation in 412 patients with primary lung cancer. CT
      scanning was also performed and we compared the extraosseous uptake by lung
      cancer with the internal structure of the tumor on CT scans. The extent of
      ectopic 99mTc-HMDP accumulation was classified as low, moderate or high. CT scans
      were used to evaluate the size and internal structure of the tumor, including
      calcification and necrosis. Ectopic 99mTc-HMDP accumulation in primary lung
      cancer was found in 32 patients (7.7%), and included 2 cases (0.5%) of high
      uptake, 8 cases (1.9%) of moderate uptake, and 22 cases (5%) of low uptake. No
      difference in uptake was observed among the histological types, but a
      relationship between tumor size and 99mTc-HMDP extraosseous accumulation was
      observed. CT scans of the 32 tumors exhibiting ectopic 99mTc-HMDP accumulation
      revealed 5 cases of calcification in the tumor and 18 cases of tumor necrosis.
      The factors promoting ectopic 99mTc-HMDP accumulation were considered to be tumor
      size and calcification or necrotic change. In patients with neither calcification
      nor necrosis, other factors such as increased calcium metabolism and altered
      vascular permeability may be involved.

PMID- 8883710
TI  - Tl-201 uptake and retention in a Warthin's tumor.
AB  - We report scan findings of Tl-201 in a case of histologically proved Warthin's
      tumor. Dual isotopes acquisition was performed in a case of left parotid
      Warthin's tumor. Both early and delayed Tc-99m-pertechnetate (Tc-99m) images
      showed increased uptake at the tumor. Tl-201 scan also showed an increase of
      uptake on the early image and retention on the delayed image. The uptake ratios
      of Tl-201 were 3.0 (early) and 2.3 (delayed). Scan findings of Tl-201 in a case
      of Warthin's tumor were similar to those of Tc-99m, and the interpretation of Tl
      201 images should be accompanied with Tc-99m images.

PMID- 8883711
TI  - Early massive accumulation of In-111 pentetreotide in a metastatic liver tumor of
      islet cell carcinoma.
AB  - A 62-year-old woman was examined with In-111 pentetreotide and Ga-67 citrate. She
      had undergone an operation to resect a neuroendocrine tumor of the pancreas and
      still had masses in the liver. One of her hepatic lesions had been biopsied and
      acinar cell carcinoma was suspected. Fluid in the cyst of the tumor, however,
      contained a high concentration of gastrin and the tumor was strongly suspected of
      being a metastasis from the neuroendocrine tumor of the pancreas. The hepatic
      tumors quickly accumulated In-111 pentetreotide immediately after the injection,
      but there was no Ga-67 citrate uptake in the tumor. Five months after
      pentetreotide scintigraphy, her hepatic tumors were resected and histologically
      proven to be metastasis of islet cell carcinoma. In-111 pentetreotide provides
      information of the somatostatin-receptor status on the tumor and supports the
      diagnosis made by hormonal survey.

PMID- 8883712
TI  - Nasal mucosal thickening simulating a tumor: potential for misdiagnosis in brain
      perfusion imaging.
AB  - A 33-year-old, female presenting with dementia was admitted to our institution.
      Except for slight muscle atrophy noted on both lower extremities there were no
      other significant physical signs or laboratory findings. Since initial Tc-99m
      HMPAO SPECT showed hypoperfusion on both temporal, parietal and occipital lobes,
      follow up study with the same radiotracer was done. Increase in uptake was noted
      in the left side of the face. There was no abnormality noted on ENT examination.
      CT scan and MRI showed slight nasal mucosal wall thickening. T1-201 SPECT showed
      increased uptake in the nasal area. The increase in uptake could be due to nasal
      mucosal thickening. This could simulate nasal tumor and interfere in determining
      ROI for brain perfusion studies.

PMID- 8883713
TI  - Accumulation of Tc-99m HMDP in hepatic metastasis from colon carcinoma without
      detectable calcification.
AB  - A 51-year-old man was found to have hepatic metastasis from colon carcinoma. Bone
      scintigraphy with 99mTc-hydroxymethylene diphosphonate showed a ringlike
      accumulation corresponding to the hepatic mass, which was without calcification
      on computed tomography. Treatment with chemotherapeutic agents was started. After
      4 months, computed tomography showed that the mass was smaller than before and
      that the margin was calcified. The extraosseous accumulation of the radionuclide
      may be evidence supporting earlier speculation on calcification that could not
      yet be detected by computed tomography.

PMID- 8883714
TI  - Inguinoscrotal lymphatic reflux detected by lymphoscintigraphy.
AB  - We performed lymphoscintigraphy with 99mTc-human serum albumin in a case of
      suspected lymphedema of the right leg after inguinal lymph node dissection.
      Dermal backflow of the leg and lymphocele at the inguinal chain were observed,
      and lymphatic reflux into the scrotum was also delineated. The scintigraphy could
      demonstrate a persistent lymphatic problem under conservative treatment, and
      could lead the physician to conduct surgical treatment. Scintigraphic
      demonstration of the inguinoscrotal lymphatic reflux has not been previously
      reported.

PMID- 8883715
TI  - Brain perfusion SPECT in neuro-Behcet's disease: discordance between Tc-99m-HMPAO
      and Tc-99m-ECD.
AB  - A patient with neuro-Behcet's disease was studied with both Tc-99m-HMPAO and Tc
      99m-ECD brain perfusion SPECT during the same time period. In Tc-99m-HMPAO SPECT,
      focal high uptake was observed in the left basal ganglia where MRI depicted
      abnormal signal intensity. Conversely, Tc-99m-ECD SPECT did not show
      corresponding high uptake, but demonstrated rather low uptake in contrast to the
      Tc-99m-HMPAO SPECT. This case suggests that Tc-99m-HMPAO and Tc-99m-ECD may show
      discordant distribution in inflammatory brain disease such as neuro-Behcet's
      disease.

PMID- 8883716
TI  - Thyroid hormone-free albumin: charcoal treatment or resin treatment.
AB  - Free thyroid hormone measurement by means of immunoassay kits is greatly
      influenced by the altered serum albumin and free fatty acid (FFA) levels. In the
      evaluation of these kits, it is therefore essential to study the interferences
      due to these factors by adding FFA or thyroid hormone-free human serum albumin
      (HSA) to the assay mixture, but little attention has been paid to the selection
      of albumin. In the present study, FFA content in various preparations of thyroid
      hormone-free HSA was compared. Charcoal-treated HSA was free from both thyroid
      hormone and FFA, whereas anion exchange resin-treated HSA was only free from
      thyroid hormone. Commercially available "FFA-free HSA" was also free from thyroid
      hormone. Our results suggest that attention must be paid to the nature of albumin
      when studying the interference by albumin in free thyroid hormone measurement and
      that commercially available "FFA-free HSA" is a ready-to-use thyroid hormone-free
      HSA when HSA free from both FFA and thyroid hormone is desired.

PMID- 8883718
TI  - Hazard ratio for thyroid carcinoma.

PMID- 8883717
TI  - Evaluation of the brain uptake properties of [1-11C]labeled hexanoate in
      anesthetized cats by means of positron emission tomography.
AB  - Positron emission tomography (PET) was performed on the cat brain to characterize
      [1-11C]hexanoate and other [1-11C]labeled short and medium-chain fatty acids as a
      tracer of fatty acid oxidative metabolism. After an intravenous injection the
      brain uptake of [1-11C]hexanoate reached a peak followed by rapid washout until 2
      min (first phase). Subsequently the total brain uptake was again increased and
      reached to a peak 7-10 min after tracer injection (second phase). The blood
      radioactivity of unmetabolized [1-11C]hexanoate was rapidly decreased and almost
      eliminated within the first 2 min, whereas the blood radioactivity of
      [11C]CO2/HCO3- was gradually increased and reached a peak approximately 5 min
      after tracer injection. As the effect of circulating [11C]CO2/HCO3- was examined
      by a bolus intravenous injection of [11C]CO2/HCO3-, the brain uptake of
      [11C]CO2/HCO3- was rapidly increased right after the injection and changed
      parallel to the blood level of [11C]CO2/HCO3-. These results suggest that, in
      contrast to the previous mouse data, the time-activity curve in the cat brain
      following intravenous injection of [1-11C]hexanoate has a biphasic pattern, the
      second phase being determined by peripherally originating [11C]CO2/HCO3-, and
      therefore does not reflect the metabolism of 11C-labeled fatty acid in the brain.

PMID- 8883719
TI  - Medical ethics under managed care: how can the patient survive?
AB  - Traditional medical ethics is based on the relationship between the individual
      physician and his or her patient. Managed care organizations, particularly under
      capitation, threaten this relationship, raising concerns about conflicts of
      interest between doctor and patient. In order to reconcile the divergent
      political, institutional, and professional points of view regarding managed care,
      a model of medical ethics relying on the concept of social justice is proposed.

PMID- 8883720
TI  - Effect of electrosurgical technique on wound healing and early complication rate
      following abdominal dermolipectomy.
AB  - Thirty-eight patients with significant weight loss after vertical banded
      gastroplasty were studied prospectively while undergoing abdominal dermolipectomy
      to determine if the current intensity used during electrosurgical dissection
      influenced wound complication rates after this surgery. Patients were assigned
      randomly to one of two groups: (1) a HI group, in which the electrosurgical
      current intensity was set at a level that easily allowed coagulation of all
      vessels smaller than 0.5 mm in diameter or (2) a LO group, in which the current
      intensity was set at a much lower level that allowed dissection, but required
      that nearly all visible vessels be ligated separately. A standardized procedure
      was employed for all patients. The patients in the LO (N = 14) and HI (N = 24)
      groups were well matched for age, weight history, nutritional parameters,
      operative times, surgical blood loss, and postoperative hospital stay. The
      overall complication rates of 36% and 21%, and wound complication rates of 36%
      and 13% for the LO and HI groups, respectively, were not significantly different.
      These data indicate that using a relatively high electrosurgical current
      intensity for dissection during abdominal lipectomy does not result in a higher
      wound complication rate.

PMID- 8883721
TI  - Are the palmar cutaneous nerves safe during standard carpal tunnel release?
AB  - An incision in the axis of the ring finger is thought to be the safest for carpal
      tunnel release based on cadaveric studies that suggest that the palmar cutaneous
      nerves do not cross into this area. Despite the use of this incision, persistent
      postoperative scar tenderness has been reported in up to 36% of patients
      following standard carpal tunnel release. For this reason, an investigation was
      undertaken to determine the presence of palmar cutaneous nerves in this incision.
      Random biopsies of transversely oriented fibrous bands in the subcutaneous tissue
      were taken during 15 open carpal tunnel releases. In every patient, at least one
      biopsy was positive for peripheral nerve tissue. These findings, combined with
      previous cadaveric studies, suggest that a "safe" palmar incision that will avoid
      injury to palmar cutaneous nerves does not exist. Carpal tunnel release
      techniques that avoid a palmar incision may lessen postoperative morbidity by
      avoiding injury to these small cutaneous nerves.

PMID- 8883722
TI  - Is training in endoscopic carpal tunnel release appropriate for residents?
AB  - Based on the relatively high incidence of complications for surgeons initially
      learning the technique, endoscopic carpal tunnel release is thought to have a
      steep learning curve. To determine if endoscopic carpal tunnel release can be
      safely performed by trainees, the outcomes of 84 patients who underwent
      endoscopic carpal tunnel release performed by a chief resident or hand fellow in
      a supervised setting were reviewed. All but 1 patient had uneventful procedures
      and complete resolution of preoperative symptoms. One patient with persistent
      symptoms represented the only complication. At reexploration through a standard
      palmar incision, the transverse carpal ligament was found to have been completely
      divided and fulminant tenosynovitis surrounding the nerve and flexor tendons was
      presumed to be the cause of his persistent symptoms. It appears that endoscopic
      carpal tunnel release can be safely performed by chief residents in a supervised
      clinical setting. Given that this procedure has a high learning curve, repeated
      exposure during a residency training program may offer significant advantages
      over the current approach of training surgeons during a single cadaveric
      instructional course.

PMID- 8883723
TI  - Aesthetic breast reconstruction using a combination of free transverse rectus
      abdominis musculocutaneous flaps and breast implants.
AB  - Some women electing immediate bilateral postmastectomy breast reconstruction have
      inadequate autologous tissue to achieve an aesthetic result and also wish to
      avoid tissue expansion or a back scar. These patients are candidates for
      reconstruction using free transverse rectus abdominis musculocutaneous (TRAM)
      flaps and breast implants. Since November 1993, 5 women have been reconstructed
      bilaterally with a combination of free TRAM flaps and adjustable saline breast
      implants. Each patient was young (age, 29-47 years) and of slender body habitus.
      During the procedure, the implants were placed in a submuscular pocket formed by
      the pectoralis major, the serratus anterior, and the muscular portion of the TRAM
      flap. Careful approximation of the serratus anterior to the lateral border of the
      pectoralis major muscle created a reliable layer of tissue to protect the
      vascular pedicle of the TRAM flap from contact with the implant. The saline
      chambers of the implants were filled to 60% to 80% capacity at the time of
      surgery. TRAM flap skin was tailored to precisely replace missing breast
      envelope, and subcutaneous fat increased implant coverage, creating a mound with
      normal-appearing ptosis. There were no occurrences of microvascular thrombosis.
      Three patients experienced prolonged formation of serous fluid, with 2 patients
      requiring late aspiration of a serosa after drain removal. Although there were no
      documented infections, 1 patient experienced postoperative erythema of the
      mastectomy skin flaps and was treated empirically with antibiotics with
      resolution of the erythema. All breasts have remained soft and appear natural.
      Using free TRAM flaps and adjustable saline breast implants allows selected women
      to undergo immediate breast reconstruction without the need for prolonged tissue
      expansion or back scars. Aesthetic results are excellent and the immediate use of
      an implant does not appear to pose a risk to the success of the free tissue
      transfer.

PMID- 8883724
TI  - The seven deadly sins of statistical analysis.
AB  - In a pedantic but playful way, we discuss some common errors in the use of
      'statistical analysis' that are regularly observed in our professional plastic
      surgical literature. The seven errors we discuss are (1) the use of parametric
      analysis of ordinal data; (2) the inappropriate use of parametric analysis in
      general; (3) the failure to consider the possibility of committing type II
      statistical error; (4) the use of unmodified t-tests for multiple comparisons;
      (5) the failure to employ analysis of covariance, multivariate regression,
      nonlinear regression, and logistical regression when indicated; (6) the habit of
      reporting standard error instead of standard deviation; and (7) the underuse or
      overuse of statistical consultation. Confidence and common sense are advocated as
      a means to balance statistical significance with clinical importance.

PMID- 8883725
TI  - Human immunodeficiency virus infection and subsequent melanoma.
AB  - Immunosuppression has been known for many years to be associated with the
      development of skin cancer, particularly squamous cell carcinoma. The association
      with melanoma is less clear. This report describes 4 patients with known human
      immunodeficiency virus (HIV) positivity who subsequently developed malignant
      melanoma. The subtypes and precursors of the tumors vary. Three of 4 patients
      treated using accepted surgical standards remained disease free an average of 33
      months postoperatively. Treatment of the melanoma as in the non-HIV infected
      melanoma patient is advised. Epidemiological studies remain to be done to
      determine the significance of this association. In the meantime, melanoma remains
      a surgical disease and early, aggressive, standard surgical treatment is
      encouraged for these patients. Despite the immunocompromised state that their HIV
      status implies, surgical treatment offers local and regional control of disease
      and possibly cure.

PMID- 8883726
TI  - The diagnostic value of magnetic resonance imaging in combination with
      angiography in patients with vascular malformations: a prospective study.
AB  - Vascular birthmarks are common lesions that can be divided into hemangiomas and
      vascular malformations (arterial, venous, capillary, and lymphatic malformations
      or a combination of these, according to Mulliken. Thirty-four patients with a
      vascular malformation were evaluated prospectively with magnetic resonance
      imaging (MRI) during a 6-year period in a combined study of the departments of
      radiology and plastic and reconstructive surgery. Hemangiomas were not part of
      this study, as they regress spontaneously in childhood. MRI and angiographic
      findings are described and the value of MRI is investigated for its usefulness in
      conjunction with angiography. MRI turns out to be superior as the initial
      diagnostic test for vascular malformations. Further investigations are not
      necessary in low-flow lesions. In case of high-flow and combined-flow lesions,
      angiography is indicated following MRI to show the exact angioarchitecture, which
      is essential for therapy planning. A flowchart, based on radiodiagnostic
      features, is proposed for diagnostic evaluation of patients with vascular
      birthmarks.

PMID- 8883727
TI  - Prolonged survival in patients with advanced melanoma treated with neoadjuvant
      chemotherapy followed by resection.
AB  - Patients with metastatic melanoma (AJCC stage IV) generally have a very poor
      prognosis (median survival, 6-8 months). Combination chemotherapy is often the
      treatment of choice. Despite the higher response rates of a number of new
      combination regimens, the median duration of response ranges from 6 to 9 months,
      with no significant survival advantage. To evaluate whether surgical resection of
      residual metastases after chemotherapy can improve survival, we conducted a
      retrospective analysis of all patients enrolled on various chemotherapy protocols
      for metastatic melanoma at Yale between March 1987 and March 1993. We identified
      16 patients who underwent surgical resection of residual disease after receiving
      one to four cycles of combination chemotherapy. Sites of metastases included
      regional and distant lymph nodes, skin, subcutaneous tissue, lung, and liver. No
      patients had brain or bone metastases at the initiation of therapy and
      performance status (PS) was 0.1. Follow-up for these 16 patients ranges from 14
      to 62 months (median, 35 months) from the start of chemotherapy. All 16 patients
      had either complete responses (CR = 3) or partial responses (PR = 7), or stable
      disease (SD = 6) after chemotherapy. Eleven patients are currently alive; 10
      remain free of disease. A comparison group (control) of 14 patients was
      identified from the same retrospective analysis using similar clinical
      characteristics such as sites of metastases, PS, and cycles of chemotherapy. No
      patients underwent surgical resection either because of patient refusal or
      concomitant medical problems. None had evidence of disease progression (CR = 3,
      PR = 2, SD = 9) at the completion of chemotherapy. However, duration of survival
      in this group from the start of chemotherapy ranged from 4 to 45 months (median,
      11.5 months). Twelve patients have died and 2 are currently alive, 1 of which has
      recurrent disease. Based on the comparison of these two groups, this report
      suggests that patients treated with neoadjuvant chemotherapy may benefit from
      surgical resection of residual metastases, and this approach should be studied
      further.

PMID- 8883728
TI  - Gluteus maximus musculocutaneous flap for the treatment of recalcitrant pilonidal
      disease.
AB  - Although conservative surgery should be the initial approach to pilonidal
      disease, there remains a select group of patients with recalcitrant disease who
      fail repeated interventions and for whom a more aggressive approach is justified.
      Use of a large gluteus maximus musculocutaneous flap to facilitate wide excision,
      to allow for primary closure with well-vascularized tissue, and to alter the
      anatomy of the gluteal cleft has been used in 5 patients with chronic recurrent
      recalcitrant disease. The use of this large muscle unit in these otherwise
      healthy adults has achieved control over their pilonidal disease with acceptable
      morbidity and no demonstrable functional sequelae.

PMID- 8883729
TI  - Flap prefabrication: effectiveness of different vascular carriers.
AB  - A new experimental model of a vascular carrier to prefabricate a "secondary"
      island flap, the popliteal musculovascular pedicle, was developed in the rat.
      Using quantitative skin-surface fluorometry 30 minutes after sodium fluorescein
      injection and a flap survival area in the prefabricated 8 x 2.5-cm abdominal
      composite island flap, we compared the revascularization ability of our muscular
      carrier to nonrevascularized controls: the skeletonized arteriovenous pedicle and
      the fasciovascular pedicle. The free composite graft with no vascular carrier
      exhibited near-total necrosis. The skeletonized vascular pedicle demonstrated
      15.2% +/- 7.8% perfusion of normal skin on dye fluorescence index measurements
      and 50% flap survival. The fasciovascular pedicle exhibited better
      revascularization, with a dye fluorescence index of 36.2 +/- 15.5 (p < 0.01) and
      90% +/- 10% flap survival (p < 0.001). India ink injection study and histological
      examination of our model provided visual evidence of revascularization from the
      musculovascular pedicle, along with preservation of the carrier's muscular
      architecture. The musculovascular pedicle is a reliable carrier for making new,
      vascularized composite flaps.

PMID- 8883730
TI  - Endothelin-1 kinetics in plasma, urine, and blister fluid in burn patients.
AB  - Endothelin-1, a peptide isolated from vascular endothelial cells, facilitates the
      constriction of vascular smooth muscle and various pharmacological actions
      including vasodilation, the proliferation of smooth muscle cells and fibroblasts,
      and the stimulation of arachidonic acid metabolism. In this study, plasma, urine,
      and blister fluid endothelin-1 concentrations were determined in burn patients
      and changes in vasoactive substances derived from endothelial cells secondary to
      burns were investigated. Plasma endothelin-1 concentrations in burn patients were
      significantly lower than those in healthy individuals at rest. However, extremely
      high blister fluid endothelin-1 concentrations were observed within 30 hours of a
      burn. The amounts of endothelin-1 excreted in urine by burn patients over 24
      hours also were higher than those in healthy individuals. The finding of high
      concentrations of endothelin-1 in blister fluids suggests that endothelin-1 is
      produced at wound regions in burn victims. Clinically, it appears that endothelin
      1 is involved in circulation at the wound surface or in the healing of burns.

PMID- 8883731
TI  - Soft-tissue coverage of the neural elements after myelomeningocele repair.
AB  - We retrospectively reviewed all newborns with a diagnosis of myelomeningocele
      (MMC) admitted to our hospital between January 1990 and September 1994 to
      determine methods of soft tissue coverage, complication rates, and results. Sixty
      five patients underwent repair of thoracic, lumbar, or sacral MMCs. The average
      size of defect repaired measured 21.3 cm2 (range, 2-80 cm2). Methods of repair
      included direct approximation of soft tissues with or without undermining (N =
      48), Romberg Limberg flaps (N = 8), gluteus maximus or latissimus dorsi
      musculocutaneous flaps (N = 5), fascioutaneous flaps (N = 3), and V-gamma
      advancement (N = 1). A total of 18 complications were recorded (27.7%). There
      were 5 major complications (7.7%) and 13 minor ones (20.0%). Major complications
      were defined as midline wound dehiscence overlying the neural elements or wound
      infection leading to meningitis or ventriculitis. All 5 major and 9 minor
      complications arose in patients undergoing direct soft-tissue approximation.
      Additionally, all major complications were recorded in defects > 18 cm2. Based on
      this series, it appears that MMC defects < 18 cm2 can be closed by direct
      approximation of soft tissues without significant risk or major wound
      complication. Larger wounds may be successfully closed in this manner, but the
      risk of major complication is substantial.

PMID- 8883732
TI  - Endoscope-assisted rectus abdominis muscle flap harvest for chest wall
      reconstruction: early experience.
AB  - We performed endoscope-assisted rectus abdominis muscle flap harvests on 2
      patients with anterior chest wall defects. For the procedure, a spindle-shaped
      anterior fascia and the upper two-thirds of the rectus abdominis muscle were
      elevated endoscopically from an incision at the umblicus and transferred to the
      chest wall defect through a subcutaneous tunnel. Endoscopic harvest of the rectus
      abdominis muscle flap minimizes postoperative scarring caused by cutting off the
      flap, affording expectations of good cosmetic results. Furthermore, this surgical
      procedure is less invasive, relieves postoperative pain, and enables reduction of
      donor site morbidity.

PMID- 8883733
TI  - A 32-year follow-up of lunate excision for Kienbock's disease: a case report and
      a review of results from excision and other treatment methods.
AB  - Lunate excision alone is seldom utilized in the management of Kienbock's disease
      due to concerns about progressive carpal collapse following removal of this
      central carpal bone. We report a 32-year follow-up of a patient who underwent
      lunate excision only for treatment of Kienbock's disease with a successful
      outcome. Although lunate excision is thought to be associated with a high failure
      rate, a review of the literature suggests that success rates following lunate
      excision are comparable to those reported for other more conventional techniques
      such as radial shortening, ulnar lengthening, limited carpal fusions, and
      proximal row carpectomy. The current perception that lunate excision is
      associated with a high failure rate is not supported in the literature. As such,
      it may not be appropriate to assign this operation to the category of "historical
      interest only."

PMID- 8883734
TI  - A technique for the repair of simple congenital earlobe clefts.
AB  - Congenital cleft of the earlobes is rarely seen among congenital ear anomalies.
      These clefts show a wide range of severity and localization, from simple notching
      to extensive tissue deficiencies. We developed a new technique that can be used
      in simple cases of earlobe cleft. For this technique, we use the anterior and
      posterior parts of the cleft as Y-V advancement flaps and achieve a three
      dimensional construction of the lobe that is symmetrical with the opposite lobe.

PMID- 8883735
TI  - Coumadin necrosis of the skin: report of four patients.
AB  - Necrosis of skin and soft tissue as a complication of oral anticoagulation
      therapy is a rare condition with approximately 200 cases documented in the world.
      Coumadin-induced skin necrosis is a painful skin lesion, sudden, localized,
      initially erythematous or hemorrhagic, that becomes bullous and eventually
      culminates in gangrenous necrosis. It develops mainly in women around 50 years of
      age who are usually obese and have been treated for thrombophlebitis or pulmonary
      embolism. There seems to be a marked predilection for areas with increased
      subcutaneous fat content, such as breasts, thighs, and buttocks. The injury is so
      significant that plastic surgery is frequently required to repair the damaged
      tissue. The authors present four clinical cases of Coumadin necrosis, observed in
      two different institutions, and perform a literature review on the mechanisms
      that trigger the development of the disease. This condition still remains a
      diagnostic-therapeutic challenge.

PMID- 8883736
TI  - V-Y advancement posterior thigh fasciocutaneous flaps for total anal canal and
      large perianal defects.

PMID- 8883737
TI  - Re: Reduction mammaplasty: an outcome analysis.

PMID- 8883738
TI  - Re: Needle localization breast biopsy with reduction mammaplasty.

PMID- 8883739
TI  - Re: The surgically delayed unipedicled TRAM flap for breast reconstruction.

PMID- 8883740
TI  - Re: Scarpa's adipofascial flap for repair of wide scalp defects.

PMID- 8883741
TI  - Effects of acute overdose of vitamin A on the hepatic content of K, Na, Mg, Fe,
      Cu and Zn, in rats.
AB  - Interactions among vitamin A metabolism and several metals have been reported in
      both normal and pathological situations. In the present report we studied, in
      rats, the effect of daily injections of 100.00 U.I. of vitamin A during seven
      days on the content of K. Na, Mg, Fe, Cu and Zn in the whole liver. The results
      were compared with the findings in pair-fed non-treated animals (Control Group).
      The mean +/- SEM for the concentrations of these elements in the control group
      were 3.433 +/- 234 (K), 649 +/- 19 (Na), 239 +/- 5 (Mg), 169 +/- 7 (Fe), 5 +/-
      0.1 (Cu) and 31 +/- 2 (Zn) ug/g wet tissue, respectively. The hypervitaminosis A,
      confirmed by a significant increase in tissue concentration of the vitamin,
      altered the hepatic content of the above mentioned cations. While Na and Zn
      increased, the other cations decreased its concentrations in the whole liver.
      Possible mechanisms for these findings are discussed and it is concluded that
      high doses of vitamin A result in marked changes in the hepatic content of the
      studied metals.

PMID- 8883742
TI  - What happens to women with preeclampsia? Microalbuminuria and hypertension
      following preeclampsia.
AB  - There is little published data on the incidence of remote hypertension,
      microalbuminuria (a possible marker of remote cardiovascular events) and diabetes
      following preeclampsia. This is of particular importance in Pacific Island
      populations as they have a high rate of preeclampsia, non-insulin dependent
      diabetes and cardiovascular related deaths. The aim of this study was to compare
      the rate of microalbuminuria and hypertension in 50 Samoan women with past
      preeclampsia (cases) with 50 Samoan women who did not have past preeclampsia
      (controls). Forty per cent of cases were hypertensive at follow-up compared to 2%
      in the control group (p < 0.0001). Microalbuminuria or proteinuria occurred in
      40% of women with past preeclampsia and 18% of controls (p < 0.02). Half of the
      cases with microalbuminuria were hypertensive. No case or control had an elevated
      fructosamine, suggesting that current diabetes was an unlikely explanation for
      the microalbuminuria. We conclude that Samoan women with past preeclampsia are at
      increased risk of developing chronic hypertension and microalbuminuria. The
      significance of the microalbuminuria after preeclampsia is not known, but it may
      be a marker of either remote cardiovascular morbidity or non-insulin dependent
      diabetes. This study raises longterm health implications for women with
      preeclampsia.

PMID- 8883743
TI  - Identification and treatment of women with hyperglycaemia diagnosed during
      pregnancy can significantly reduce perinatal mortality rates.
AB  - We wished to determine whether gestational diabetes was associated with an
      increased perinatal mortality rate, and to investigate the cause for the observed
      increase in the incidence of gestational diabetes. We therefore reviewed the
      results of glucose tolerance tests and pregnancy outcome in 116,303 pregnancies,
      1971-1994, at the Mercy Hospital for Women. The main outcome measurements were
      the presence or absence of gestational diabetes, and perinatal mortality. Over
      the entire period of the study, gestational diabetes was associated with an
      increased risk of perinatal mortality (Mantel-Haenszel adjusted odds ratio 1.53,
      95% CI 1.13-2.06, p = 0.0069). Women with gestational diabetes that was only
      diagnosed retrospectively had a higher perinatal mortality rate than their
      contemporaries with normal glucose tolerance (OR 2.31, 95% CI 1.37-3.91, p =
      0.0025). Women in whom a glucose tolerance test was not performed continued to
      have a higher perinatal mortality rate than women who were tested (adjusted OR
      2.21, 95% CI 1.56-3.12, p < 0.00001). There has been an increase in the
      prevalence of gestational diabetes from 2.9% to 8.8%. Some of this is due to
      changes in population characteristics (increases in maternal age, obesity and
      proportion from South-East Asia), but there was still an independent increase
      over time. We conclude that identification and treatment of women with
      gestational diabetes can reduce perinatal mortality rates. Similarly to diabetes
      mellitus in the total population, the prevalence of gestational diabetes has
      increased over time.

PMID- 8883744
TI  - Impaired glucose tolerance in pregnancy--is it of consequence?
AB  - This study was done to determine if impaired glucose tolerance in pregnancy was
      associated with increased maternal and neonatal morbidity and if so, whether the
      increased morbidity was due to the confounding factors of increased maternal age
      and maternal obesity. It was a retrospective analysis to compare 944 women with
      impaired glucose tolerance (IGT) in pregnancy with 10,065 women without abnormal
      glucose tolerance. The incidence of impaired glucose tolerance in pregnancy was
      8.6% in this study. Even when maternal age and obesity were excluded, the IGT
      group had significantly higher risks of labour induction (relative risk, RR,
      1.15); Caesarean section (RR: overall 1.43, elective 1.72, emergency 1.31);
      Caesarean section for dystocia/no progress (RR 1.60); macrosomia (RR 1.69, 1.76,
      1.61 for birth-weight > = 97th, 95th, 90th percentiles respectively) and shoulder
      dystocia (RR 2.84) when compared to the nondiabetics (NDM). The risks of
      hypertensive disease (RR 1.22) and Caesarean section for fetal distress/thick
      meconium-stained liquor (RR 1.53) were also higher in the IGT group but these
      increases were not statistically significant when maternal age and obesity were
      excluded. There was no significant difference in the rates of low Apgar scores at
      1 and 5 minutes between the 2 groups.

PMID- 8883745
TI  - Free fatty acids and gestational diabetes mellitus.
AB  - Dyslipidaemia is a common finding in the syndrome of gestational diabetes
      mellitus (GDM). Free fatty acids (FFA) can cause insulin resistance and have a
      toxic effect on beta cell function. GDM is a syndrome due to insulin resistance
      and the purpose of this study was to examine FFA levels in pregnancy. For this
      purpose samples were taken from 44 consecutive women with GDM and 36 consecutive
      controls. The women with GDM had similar levels of insulin, triglycerides and
      total cholesterol to the controls but a significant elevation in FFA; 0.70 (0.33)
      mmol/L versus 0.29 (0.12) mmol/L (p < 0.0001).

PMID- 8883746
TI  - Eclampsia in Kuwait 1981-1993.
AB  - The aim of this study is to investigate the maternal and fetal outcome and the
      risk factors for developing eclampsia in Kuwait. The study includes all patients
      with eclampsia observed at the Maternity Hospital, Kuwait during the period from
      1981 to 1993. It revealed that the risk factors predisposing to eclampsia were
      primiparity, a maternal age below 30 years, multiple pregnancy and the presence
      of preeclampsia. The pregnancy outcome in terms of the stillbirth rate, neonatal
      death rate and low birth-weight babies was significantly higher in mothers with
      eclampsia than in noneclamptic mothers. The operative delivery and maternal
      mortality rates were also significantly higher in these patients.

PMID- 8883747
TI  - A review of eclampsia in Melbourne: 1978-1992.
AB  - A retrospective review of all cases of eclampsia diagnosed at 3 obstetric
      teaching hospitals in Melbourne from January, 1978 to December, 1992 was
      undertaken. Ninety cases were identified; there were 5 maternal deaths and 17
      perinatal deaths. Severe maternal morbidity such as pulmonary oedema, acute renal
      failure or HELLP syndrome was found in 26%. Significant maternal thrombocytopenia
      (< 100 x 10(9)/L) was found in 50% and 35% had abnormal maternal liver function
      tests. Forty six women received magnesium sulphate for treatment of eclampsia and
      of these 3 had further seizures compared to 4 of 18 who received phenytoin (odds
      ratio 0.24 (0.04-1.52) X2, p = 0.09). Eclampsia remains a significant
      complication of pregnancy with high maternal and perinatal mortality and
      morbidity. Results of this study show a trend that is in agreement with recent
      randomized controlled trials which demonstrate a reduced incidence of seizures
      and maternal and fetal complications with the use of magnesium sulphate. The
      results of these recent trials suggest that magnesium sulphate should be the drug
      of choice in the prevention and treatment of eclampsia.

PMID- 8883749
TI  - The effect of epidural bupivacaine on the fetal electrocardiogram.
AB  - Fetal electrocardiogram waveform analysis was used to assess the effect of
      epidural bupivacaine on the fetal myocardial conducting system by evaluating its
      effect on the PR interval, RR interval, T/QRS ratio and the PR-RR correlation
      coefficient. There were no significant changes in either the PR interval or the
      PR-RR correlation coefficient. There was a significant increase in the fetal
      heart rate and a significant fall in the T/QRS ratio. Epidural bupivacaine does
      not alter fetal myocardial conduction as measured by the PR interval and it does
      not induce ischaemic cardiac changes as assessed by the T/QRS ratio.

PMID- 8883748
TI  - Actions of magnesium, nifedipine and clonidine on the fetal vasculature of the
      human placenta.
AB  - The anticonvulsant magnesium and the antihypertensives clonidine and nifedipine
      are extensively used for the clinical treatment of preeclampsia and eclampsia.
      Little, however, is known about the possible effects of these agents on human
      fetal-placental vascular resistance. We therefore examined the actions of these
      agents on the human fetal placental vascular bed in vitro relating the
      concentrations causing any vasoactive effects to the maternal blood levels
      attained during treatment. Placentas (n = 24) were obtained within 20 minutes of
      delivery from women (aged 30.2 +/- 0.9 years). In each a placental lobule was
      bilaterally perfused with Krebs' solution (5 mL/minute, 37 degrees C, 95% O2, 5%
      CO2) and fetal arterial inflow pressure (FAP) monitored. Submaximal
      vasoconstriction of the fetal vascular bed was induced by continuous infusion of
      prostaglandin F2 alpha (4.2 +/- 0.5 microM) which increased FAP from 25.9 +/- 3.9
      to 95.1 +/- 6.2 mm Hg. Using a group of placentas for each drug, the effects of
      MgCl2, nifedipine and clonidine, were examined. Magnesium (0.3-100 mM) (n = 4)
      dilated the placental fetal circulation with an IC50 of 8.1 mM and a maximal
      response of 89.7 +/- 3.6% (n = 4). This effect of Mg2+ was not changed during
      concomitant infusion of the cyclo-oxygenase inhibitor, indomethacin (3 microM).
      Nifedipine (3-10,000 nM) also produced vasodilatation (maximum response 42 +/-
      9%, n = 5). Clonidine (3-1,000 nM) caused no significant change (p < 0.05 n = 5)
      in vascular resistance (maximum response 11.2-5.7%) relaxation), when compared to
      controls. Thus in concentrations likely to be therapeutically present in maternal
      blood, magnesium causes a greater degree of placental fetal vasodilatation than
      does nifedipine, whereas clonidine is unlikely to have any effect on fetal
      placental vascular resistance.

PMID- 8883750
TI  - Failed homebirths: reasons for transfer to hospital and maternal/neonatal
      outcome.
AB  - A review of patients who had been transferred to the Royal Women's Hospital,
      Brisbane after a failed homebirth was undertaken over a period of 5 1/2 years.
      There were 27 patients identified. The most common reason for transfer was failed
      progress in labour, although 4 patients were transferred after delivery. Despite
      the resistance of these patients to medical intervention, the study found that
      63% of patients required assistance at delivery, by vacuum extraction, forceps or
      Caesarean section. The morbidity suffered by the babies was significant (8 were
      admitted to special and intensive care nursery) but long-term sequelae cannot be
      determined because of early discharge against medical advice and refusal to be
      followed-up in some instances.

PMID- 8883751
TI  - Fearing the worst--why do pregnant women feel 'at risk'?
AB  - Whilst pregnancy and childbirth are generally regarded as a joyful and exciting
      time in a woman's life they are also filled with fear, uncertainty, a feeling of
      being 'at risk' and anxieties about what the pregnancy and future may hold. In a
      society where the perinatal and maternal mortality and morbidity rates are low,
      where do these fears and uncertainties arise from? Why do pregnant women fear the
      worst? What are the implications of this? A cross-sectional and qualitative study
      of 376 postnatal women in a major public teaching hospital in Melbourne was
      undertaken in 1995 to explore women's beliefs and fears about pregnancy and
      birthing outcomes, through their perceptions and use of routine antenatal
      screening tests. Through women's perceptions about the value of, and expectations
      of, routine antenatal screening tests, and their fears during pregnancy, the
      author explores the 'notion of risk' as perceived by these women.

PMID- 8883752
TI  - Perinatal infection with Listeria monocytogenes.
AB  - Listeria monocytogenes has been increasingly recognized as a cause of
      intrauterine sepsis with associated perinatal wastage. The condition is mostly
      acquired through dietary intake and appropriate advice should be given to all
      pregnant women. The most common presentations in pregnancy include premature
      labour, an influenza-like illness and reduced fetal movements. In this report, we
      present a series of 24 cases of perinatal listeria infection presenting to either
      our obstetric or neonatal units and confirmed by the microbiology department of
      the hospital. In particular, we wish to highlight 3 cases in which antenatal
      diagnosis and aggressive therapy was associated with a successful outcome.
      Amongst the remaining 21 cases in which an antenatal diagnosis was not made,
      there were 5 perinatal deaths and 1 mid-trimester loss at 18 weeks. Clinicians
      must maintain a high index of suspicion for listeria, particularly in gravid
      patients who present with fever in the setting of a persistent 'flu-like' illness
      and premature labour. Once suspected, appropriate specimens for listeria culture
      should include blood, cervical swabs and midstream urine. Empirical antibiotic
      therapy with amoxicillin should be instituted while waiting for culture results
      in patients with possible Listeria monocytogenes sepsis.

PMID- 8883753
TI  - Cervical ripening before induction of labour in patients with an unfavourable
      cervix: a comparative randomized study of the Atad Ripener Device, prostaglandin
      E2 vaginal pessary, and prostaglandin E2 intracervical gel.
AB  - One hundred and nineteen women with singleton pregnancy and cephalic presentation
      requiring induction of labour in the presence of an unfavourable cervix (Bishop
      score < or = 4) were studied. Five patients were excluded because of failure to
      comply with the protocol. Cervical ripening was carried out using 3 different
      methods; 36 used the Atad Ripener Device, 39 received 0.5 mg PGE2 intracervical
      gel and 39 received at least one 3 mg PGE2 intravaginal pessary. There were no
      differences in the demographic characteristics and the indications for induction.
      Five patients developed complications during the ripening period necessitating
      intervention; 3 required emergency Caesarean section and 2 delivered vaginally.
      Although statistically there were no differences among the 3 methods of cervical
      ripening, the power of the study is probably not large enough to show the
      differences. The PGE2 pessary appears to be more effective with 68% of patients
      either going into labour during cervical ripening or succeeding in the cervical
      ripening compared to around 50% in the Atad and PGE2 gel groups. The vaginal
      delivery rate was 87.2% in the pessary group compared to 72.2% in the Atad group
      and 84.6% in the gel group. The duration of labour was also shorter in the
      pessary group with 73.5% delivered within 24 hours compared to 57.7% in the Atad
      group and 57.6% in the gel group. Although the results of the Atad device seem to
      be inferior, the risk of uterine hyperstimulation from the use of the device is
      probably lower than that of the PGE2 and may therefore be preferable in women
      with fetuses at high risk of fetal hypoxia.

PMID- 8883754
TI  - A randomized trial of 2 regimens for the administration of vaginal prostaglandins
      (gemeprost) for the induction of midtrimester abortion.
AB  - The most frequently used method for second trimester termination of pregnancy is
      administration of gemeprost (16, 16-dimethyl-trans delta 2-prostaglandin E1methyl
      ester) as a vaginal pessary. This provides a safe and effective method for
      achieving abortion. The current prescribing advice is to insert the pessaries
      into the posterior vaginal fornix every 3 hours. This study compares this to a 6
      hourly regimen. The median abortion interval in the 6-hour group was shorter than
      the 3-hour group (15 versus 16 hours respectively) but the cumulative abortion
      rates were similar (98% in the 3-hour group and 91.8% in the 6-hour group). The 6
      hour group required a significantly lower total dose of gemeprost to induce
      abortion. There was no difference in the rates of side-effects in the 2 groups
      but those receiving pessaries every 6 hours required less analgesia. This study
      finds no advantage in giving gemeprost every 3 hours.

PMID- 8883755
TI  - Prolonged induction to delivery time in termination of pregnancy using 16, 16
      dimethyl-PGE1-methyl ester (gemeprost) for fetuses with a neural tube defect or
      hydrocephalus.
AB  - A retrospective study is reported comparing the induction to delivery interval
      using gemeprost for termination of pregnancy, in the second trimester, in 3
      groups of patients. It was observed that the mean induction to delivery interval
      was significantly longer in 75 pregnancies where there was a fetus with a neural
      tube defect and or hydrocephalus (31.7 hours) compared with 88 pregnancies with
      other fetal abnormalities (19.7 hours) and 84 pregnancies where there was an
      intrauterine death (11.3 hours). There was also an increase in the requirements
      for further intervention to obtain delivery in the group with a neural tube
      defect or hydrocephalus (n = 33) compared with where there was an intrauterine
      fetal death (n = 4) and other abnormality (n = 14). We believe these results
      should be considered when counselling patients who have requested termination of
      pregnancy for fetal abnormalities.

PMID- 8883756
TI  - Antepartum and postpartum complications of twin-twin transfusion.
AB  - Twin-twin transfusion is a condition that was previously associated with close to
      a 100% perinatal mortality. Recent reports suggest that a survival rate of about
      60% can be achieved with serial amniocentesis and modern neonatal care. However,
      it is now apparent that the survivors of this condition have multisystem
      complications that can result in neonatal mortality and long-term morbidity.
      Fourteen cases of twin-twin transfusion were examined to determine the antenatal
      findings that may predict the postnatal outcomes of these infants. The overall
      survival was 61% (17 of 28). The mean gestation at diagnosis was 23.0 weeks
      (range 18-34 weeks) and the mean gestation at delivery was 29.0 weeks (range 23
      37 weeks). The mean number of amniocenteses was 2.9 and the average total volume
      of amniotic fluid removed was 6,114 mL. Different patterns of complications were
      seen in the donor and recipient twins. Hypertrophic cardiomyopathy affected 9 of
      the recipient twins. Anuria/oliguria was found in 4 of the donor twins and none
      of the recipients. Periventricular leukomalacia was found in 8 twins and 7 also
      had mild ventriculomegaly; of the surviving 17 twins, 5 had either
      periventricular leukomalacia, mild ventriculomegaly or both. Amniotic fluid
      leakage and perforation of the intervening membrane subsequent to serial
      amniocentesis were seen in 5 cases. Severe intrauterine growth retardation and
      abnormal cardiotocographs were a common feature. These complications directly
      resulted in neonatal mortality and long-term morbidity in the survivors. Not all
      complications were detected antenatally and the severity was not able to be
      anticipated.

PMID- 8883757
TI  - Monoamniotic twin pregnancy and cord entanglement: a clinical dilemma.
AB  - Monoamniotic twin pregnancies are rare, but are associated with a high risk of
      perinatal death. The major complications are due to cord entanglement and twin
      twin transfusion. We were recently faced with the clinical problem of a
      monoamniotic twin pregnancy complicated by cord entanglement. Fortunately the
      outcome was favourable with the survival of both twins after delivery by elective
      Caesarean section at 32 weeks' gestation. Our case as well as some of the
      controversies in the management of this unpredictable condition are presented.
      Most authors seem to prefer abdominal delivery upon reaching fetal lung maturity
      in the case of known monoamniotic twins although this management is not validated
      by the available studies. Hospital admission for fetal monitoring upon discovery
      of a cord entanglement at a viable gestation is also advocated.

PMID- 8883758
TI  - The self-reported prevalence of postnatal depression.

PMID- 8883759
TI  - A 13-year cytogenetic study of spontaneous abortion: clinical applications of
      testing.
AB  - Chromosome analysis was performed on 1,543 specimens of first trimester
      miscarriage received between 1982 and 1994. Comparisons with earlier studies show
      that some findings are absolutely consistent between different years and
      populations, but some major differences are also found. The results are
      considered in the light of several recent genetic, environmental and
      physiological studies. Trisomy 16, and probably trisomy 22, is entirely dependent
      on maternal age; other trisomies show both maternal age and other environmental
      or genetic effects. Monosomy X and mosaic aneuploidy arise postzygotically by
      chromosome loss, a normal control mechanism. Some trisomy, dipaternal triploidy
      and tetraploidy probably occur because of pre- or postovulatory 'overripeness';
      either due to transient or chronic maternal conditions or delayed fertilization.
      Unbalanced structural abnormalities, most apparently of de novo origin, are
      markedly increased compared to earlier studies and are possibly due to paternal
      environmental exposures. It is concluded that when considering histories of
      abortion, studies of the chromosomes of the aborted products are much more
      informative and cost-effective than studies of parental bloods. Where available,
      studies of products should be undertaken for preference, but only by experienced
      and committed laboratories.

PMID- 8883760
TI  - Serum progesterone and human chorionic gonadotrophin measurements in the
      evaluation of ectopic pregnancy.
AB  - We evaluated the clinical usefulness of measuring the serum concentrations of
      human chorionic gonadotrophin (HCG) and progesterone to distinguish between early
      viable and nonviable pregnancies. We investigated 110 women with clinical
      symptoms of abnormal pregnancy. A single HCG measurement did not clearly
      distinguish between ectopic and failing intrauterine pregnancies; an HCG value
      below 3,000 IU/L, together with a serum progesterone below 40 nmol/L, predicted
      abnormal pregnancy outcome in 97% of women (positive predictive value: 91%;
      negative predictive value: 95%). Serum HCG value above 3,000 IU/L or
      progesterones above 40 nmol/L, discriminated between an ongoing pregnancy and an
      abnormal pregnancy in 87% women (positive predictive value: 95%; negative
      predictive value: 91%) and provided reassurance of an ongoing pregnancy. Our
      results suggest that a combination of serum progesterone and HCG measurements
      provide clinically useful biochemical information which enhances the prediction
      of pregnancy outcome.

PMID- 8883761
TI  - Positive Kleihauer result following an ectopic pregnancy.
AB  - The case presented highlights the risk of fetomaternal haemorrhage in ectopic
      pregnancy. With the current shortages of anti-D, it may be necessary to reduce
      administration of anti-D, but this may result in an increase in rhesus
      isoimmunization. As Kleihauer testing may be of limited value (1),
      recommendations by deCrespigny and Davison (2) for the use of a reduced dose of
      30 mcg anti-D in all rhesus negative women with early pregnancy complications
      including ectopic pregnancy, would seem appropriate.

PMID- 8883762
TI  - Serum concentrations of human chorionic gonadotrophin and immunoreactive inhibin
      in early pregnancy and recurrent miscarriage: a longitudinal study.
AB  - Serum concentrations of immunoreactive inhibin (ir-inhibin) and human chorionic
      gonadotrophin (HCG) have been measured during the first trimester in a
      longitudinal study of pregnant women attending a recurrent miscarriage clinic. In
      30 singleton pregnancies (Group 1) that continued successfully to term, the
      median concentration of ir-inhibin initially declined from 1,140 pg/mL at week 4
      5 then rose back to comparable values between weeks 7 and 10 but to decline again
      to reach the significantly lower level of 840 pg/mL (p < 0.01) at week 15-16.
      Serum levels of HCG showed the classical profile of normal pregnancy reaching a
      median peak value of 65,600 IU/L (1st IRP) at week 8-9. In 7 pregnancies that
      miscarried but earlier had evidence on ultrasound of an active fetal heart, HCG
      levels in the first 9 weeks were consistently below the 10th percentile for Group
      1 pregnancies (p < 0.001). Levels of ir-inhibin were also suppressed but to a
      lesser extent. In 6 of 7 a fetal pregnancies, HCG levels during the first 9 weeks
      were again markedly subnormal. The levels of ir-inhibin varied between high
      normal and subnormal. In none of the pregnancy groups was a correlation found
      between ir-inhibin and HCG concentrations. In a single pregnancy with an
      anencephalic fetus, while levels of ir-inhibin and HCG were not depressed, peak
      values were not reached until week 12. The study shows that the level of ir
      inhibin in the maternal serum in early pregnancy is of little value as a
      prognostic indicator of pregnancy outcome. It confirms that a subnormal HCG level
      is a useful predictor of early pregnancy failure.

PMID- 8883763
TI  - Regression pattern of beta human chorionic gonadotrophin in blood after
      chemotherapy for gestational trophoblastic neoplasia.
AB  - Although beta human chorionic gonadotrophin (beta-HCG) is a clinically-useful
      tumour marker in gestational trophoblastic neoplasia, there is limited
      information on how serum beta HCG regresses in molar pregnancy and
      choriocarcinoma during chemotherapy. The study included 41 patients who had been
      treated by single- and multidrug regimens, and decay curves for regression of
      beta HCG in the circulation in these patients were fitted to the data. Thirty
      three patients achieved a biochemical remission ('cured') by first-line
      chemotherapy; this gave an overall efficacy rate of 80%. The beta HCG decay
      curves convey useful information of the chemosensitivity of the tumour, and may
      assist in determining the time required for treatment and earlier change in
      treatment for the chemoresistant tumour.

PMID- 8883764
TI  - 1995 Brown Craig Travelling Fellowship. Destination: Ethiopia.

PMID- 8883765
TI  - The use of large loop excision of the transformation zone (LLETZ) in an
      outpatient setting.
AB  - An audit of the results of 129 patients treated in the first 12 months of
      operation of an outpatient large loop excision of the transformation zone (LLETZ)
      clinic was performed. It confirmed the efficacy of the procedure in treatment of
      cervical intraepithelial neoplasia (CIN) with a cure rate of 93.8%. Major
      deficiencies identified were the lack of compliance with recommended follow-up, a
      major discrepancy between predicted diagnosis on colposcopically directed punch
      biopsy and LLETZ specimen histology, and a large proportion of LLETZ specimens
      which had negative histology and may be regarded as overtreatment. Suggested
      strategies to address these include observation of low-grade lesions and
      treatment with LLETZ at the first clinic appointment.

PMID- 8883766
TI  - Postcoital contraception: who uses the 'morning after pill'?
AB  - Postcoital contraception (PCC) is a safe and effective method of avoiding
      unwanted pregnancy after an occurrence of unprotected sex. It nevertheless
      represents an absence or failure of preventive strategies. Women engaging in
      unprotected sex may have been exposed to risks of sexually transmissible diseases
      (STDs) including HIV/AIDS. Family planning service providers have expressed
      concern at the number of women using this emergency measure as a form of
      contraception, sometimes repeatedly, but little is known about the sort of women
      they are and the context in which unprotected sex has occurred. This paper
      reports the sociodemographic characteristics of women requiring PCC in the two
      clinical sites of Family Planning Victoria. A self-administered questionnaire was
      completed by 206 women who required PCC during a 3-month period. The women were
      aged 14-43 years with an average age of 23 years. Over half the women had used
      PCC previously and more than a quarter of these women had used it more than twice
      before. Most of the women had had sex with a regular boyfriend, husband or
      partner at their own or their partner's home. The main reasons given for needing
      PCC were nonuse of condoms, condom breakage and missing an oral contraceptive
      pill.

PMID- 8883767
TI  - Severe chronic pelvic pain in women may be caused by ligamentous laxity in the
      posterior fornix of the vagina.
AB  - The aim was to prospectively study the relationship between pelvic pain of
      otherwise unknown origin and laxity in the posterior vaginal fornix. Twenty-eight
      patients with negative laparoscopy findings, lower abdominal pain and laxity in
      the posterior ligamentous supports of the uterus underwent surgical approximation
      of their uterosacral ligaments. At 3-month review, 85% of patients were cured,
      and at 12 months, 70%. Nonorganic pelvic pain has frequently been attributed to
      psychological factors. However, the results suggest that this may be a T12-L1
      parasympathetic pain referred to the lower abdomen, perhaps due to the force of
      gravity stimulating pain nerves unable to be supported by the lax uterosacral
      ligaments in which they are contained. It was concluded that laxity in the
      posterior ligaments of the vagina should first be excluded before referring
      patients with pelvic floor discomfort or pain for psychiatric care.

PMID- 8883768
TI  - Ureteric injury at Burch colposuspension. 4 case reports and literature review.
AB  - The Burch colposuspension operation is an accepted and effective technique for
      the correction of genuine stress incontinence. It is, however, associated with a
      number of well-recognized complications. Ureteric injury at the time of
      colposuspension is a potentially severe, if uncommon, complication of this
      procedure with legal ramifications for the surgeon as well as health risks for
      the patient. To date, only 19 cases have been described in the literature. This
      paper highlights 4 cases of this injury occurring amongst the patients of 1
      urogynaecologist (2) and gives an incidence for its occurrence as well as
      discussing the aetiology and management of this complication.

PMID- 8883769
TI  - Antenatal human parvovirus B19 infection and nonimmune hydrops fetalis presenting
      as severe preeclampsia.

PMID- 8883770
TI  - Pregnancy and active Wegener granulomatosis.

PMID- 8883771
TI  - A case of acute colonic pseudoobstruction in pregnancy.

PMID- 8883772
TI  - Antenatal ultrasound diagnosis of dilated fetal bowel due to congenital chloride
      diarrhoea.

PMID- 8883773
TI  - Intrauterine retention of fetal bone.
AB  - A case of secondary infertility, dysmenorrhoea and menorrhagia due to retained
      fetal bone is presented. Retained fetal bones should be considered in all
      patients with infertility, dysfunctional uterine bleeding, dysmenorrhoea or other
      symptoms dating from a pregnancy or pregnancy termination. Ultrasound is an
      excellent modality for evaluating these patients. Ultrasound is also very useful
      for the follow-up of patients after surgical removal of the bony fragments. Some
      bony fragments may be embedded in the endometrium or myometrium and may not be
      identified at curettage. Hysteroscopy is valuable in both establishing the
      diagnosis and the removal of bony fragments. A crucial aspect of the procedure
      involves reintroduction of the hysteroscope to document that the cavity is clear
      after attempts at bone removal are complete. After removal of bony fragments,
      restoration of fertility and improvement of symptoms are expected.

PMID- 8883774
TI  - Struma ovarii presenting as acute pseudo-Meigs syndrome with an elevated CA 125
      level.
AB  - A 62-year-old woman presented with acute hydrothoraces and ascites. The CA 125
      level was greatly elevated and pelvic ultrasound revealed an adnexal mass with
      solid and cystic components. At surgery a benign pure struma ovarii was diagnosed
      and following removal of the tumour the patient had immediate and complete
      resolution of her symptoms. This is the first report of struma ovarii causing
      both pseudo-Meigs syndrome and a marked elevation of CA 125.

PMID- 8883775
TI  - Significance of mild squamous atypia (MSA) on cervical cytology.

PMID- 8883776
TI  - The early history of infectious laryngotracheitis.

PMID- 8883777
TI  - In vitro attenuation of highly virulent infectious bursal disease virus: some
      characteristics of attenuated strains.
AB  - Some strains of highly virulent infectious bursal disease virus (HV-IBDV) were
      adapted through serial passage in embryonated eggs. The embryonated egg-adapted
      HV-IBDV was successfully adapted to grow in chicken embryo fibroblast (CEF) cell
      cultures showing a cytopathic effect by preparing the CEF cells from the virus
      infected embryos. The embryonated egg- and cell culture-adapted strains
      significantly reduced their pathogenicity to, and did not kill any, young
      chickens in experimental infection. The bursal lesions of the adapted strain
      infected chickens were similar to those observed in classical strain-infected
      chickens. Cross-virus neutralization analysis showed antigenic diversity between
      the cell culture-adapted HV-IBDV strains and classical strains. In immunization
      tests, the adapted strain-immunized chickens showed good protection against the
      fatal infection of HV-IBDV. Especially, in case of challenge at 3 days
      postimmunization, the adapted strains showed effective immunogenicity. The
      adapted strains appear to provide a new and effective live vaccine against HV
      IBDV infection.

PMID- 8883778
TI  - Investigation of bacterial resistance to hatchery disinfectants.
AB  - Three commercial chicken hatcheries were sampled for environmental bacteria.
      Isolated bacteria were tested for resistance to commercial preparations of
      quaternary ammonia, phenolic, and glutaraldehyde liquid disinfectants. Bacterial
      isolates were exposed to several disinfectant dilutions bracketing the dilutions
      recommended by the manufacturer for 5-, 10-, and 15-min exposure periods before
      subculturing to broth medium. Approximately 8% of the isolates from two of three
      hatcheries were resistant to disinfectant concentrations at and above the
      manufacturers recommended dilution and time of exposure. Resistant bacteria
      included Serratia marcescens, Bacillus cereus, Bacillus thuringiensis, Bacillus
      badius, Enterococcus faecalis, Enterococcus faecium, Pseudomonas stutzeri, and
      Enterobacter agglomerans.

PMID- 8883779
TI  - Pathogenicity studies of an Arkansas variant infectious bursal disease virus.
AB  - A variant infectious bursal disease virus (IBDV), IBDV-s977, was blind passaged
      in cell culture, plaque purified, and attenuated by serial passage at a high
      multiplicity of infection (MOI) in chick embryo fibroblasts (CEF). Cell culture
      passages of virus caused less bursal atrophy and splenomegaly than did the
      original isolate and retained immunogenicity; however, virus tended to persist
      for a longer time in the bursa and spleen of birds infected with the highest CEF
      passages. Antibody to both low MOI and high MOI passages of IBDV-s977 poorly
      neutralized virus that was isolated from bursal tissue 28 days postinfection
      (PI). The spleens of chickens infected with the eighteenth CEF passage were
      negative for virus at 3 and 7 days PI but had high titers of virus at 14 and 28
      days PI. There was also more virus in the bursa of birds infected with the
      fifteenth and eighteenth CEF passages at 28 days PI than at 7 or 14 days PI.
      Defective interference (DI) was demonstrated when cell cultures were coinfected
      with a constant amount of low MOI virus and serial dilutions of high MOI virus.
      There was an increase in interference score with increased passage number in CEF,
      and there was more interference in virus passaged at a high MOI. There was an
      inverse relationship between interference score and bursal lesion score and
      splenomegaly at 7 days PI, indicating that DI particles may be involved in virus
      attenuation. There was a positive relationship between interference and viral
      persistence in the bursa and spleen at 28 days PI. Antiserum to s977 was shown to
      enhance the nonlytic replication of s977 in CEF, presumably within macrophages,
      providing a possible mechanism for the pathotypic variation seen in emerging
      strains of IBDV.

PMID- 8883780
TI  - Analysis of plasmids cloned from a virulent avian Escherichia coli and
      transformed into Escherichia coli DH5 alpha.
AB  - Three of four plasmids from a virulent wild-type avian Escherichia coli were
      cloned or transformed into an avirulent laboratory recipient E. coli DH5 alpha
      and tested for the ability to confer a virulence phenotype. The three plasmids
      transformed into E. coli DH5 alpha were 5, 6, and 56 kb. A fourth plasmid of 64
      kb was not successfully transformed. Parameters used to measure virulence
      included presence of type 1 pili and a smooth lipopolysaccharide (LPS) layer,
      motility, production of Colicin V, resistance to host complement, and embryo
      lethality. The 5-kb plasmid encoded for ampicillin resistance, whereas the 6-kb
      plasmid encoded for tetracycline resistance. The 56-kb plasmid encoded for
      streptomycin, sulfisoxazole, and tetracycline resistance. Twelve-day embryos
      inoculated with 467 colony-forming units of E. coli DH5 alpha containing the 56
      kb plasmid had increased death rates (45%) in the embryo lethality assay and a
      decreased weight of surviving embryos with cranial hemorrhages as compared with
      embryos inoculated with similar amounts of E. coli DH5 alpha (0%) and phosphate
      buffered saline (0%). Embryos inoculated with the wild-type virulent E. coli had
      90% deaths. The 56-kb plasmid also had homology with a probe for Colicin V
      production (cvaC). No differences in LPS layer, complement resistance, motility,
      Colicin V activity, type 1 pili, cell-free supernatant proteins, or outer
      membrane proteins were observed in the transformants when compared with
      nontransformed E. coli DH5 alpha.

PMID- 8883781
TI  - Lethality, hemagglutination and adhesion of Escherichia coli strains (serotype
      01) isolated in Morocco from chickens with colibacillosis.
AB  - Six strains of Escherichia coli, isolated from chickens with colibacillosis and
      belonging to serotype 01, were studied. All of them were lethal for 1-day-old
      chicks and were strongly adherent in vitro. Hemagglutination tests showed a
      strong reaction to horse and chicken erythrocytes. This reaction was inhibited by
      the addition of 5% D-mannose and also by overnight incubation at 18 C. When the
      strains were heated at 65 C or at 85 C for 1 hr, agglutination of horse and
      chicken erythrocytes was conserved only at 65 C. Purification of the subunit of
      fimbriae by several cycles of solubilization-crystallization using MgCl2 gave
      good results. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      showed that the molecular weight for one strain was about 18.4 kD.

PMID- 8883782
TI  - Impact of stocking density, breed, and feathering on the prevalence of abdominal
      skin scratches in broiler chickens.
AB  - Associations between abdominal skin scratches and stocking density, strain of
      birds, and degree of feathering were investigated in a clinical trial. Four
      hundred eighty 1-day-old male broiler chicks from two different strains (A and B)
      were assigned to four groups: 1) high density (0.07 m2/bird) and strain A, 2)
      high density and strain B, 3) normal density (0.14 m2/bird) and strain A, and 4)
      normal density and strain B. Birds were examined for scratches and feathering at
      28, 35, and 42 days of age. Two outcomes were considered for scratches: presence
      (yes/no) and severity (severe [if a deep cut or at least three superficial cuts
      were present]/not severe). Only the examination at 35 days of age was blind. The
      outcome "scratches" was significantly associated with stocking density at all
      ages (P < or = 0.0001), strain A at 28 days of age (P = 0.0480), and poor
      feathering at 35 days of age (P < or = 0.0001). The outcome "severe scratches"
      was significantly associated with stocking density at 35 (P = 0.0003) and 42 days
      of age (P = 0.0021), strain A at 35 (P = 0.0089) and 42 days of age (P = 0.0306),
      and poor feathering at 35 days of age (P = 0.0018). Stocking density, strain of
      birds, and degree of feathering could be considered as potential risk factors for
      abdominal scratches in broiler chickens.

PMID- 8883783
TI  - Influence of the host system on the pathogenicity, immunogenicity, and
      antigenicity of infectious bursal disease virus.
AB  - The effect of the host system on the pathogenicity, immunogenicity, and
      antigenicity of infectious bursal disease virus (IBDV) was investigated. One
      classic (SAL) and one variant strain (IN) of IBDV were passaged separately six
      times in three host systems, namely BGM-70 continuous cell line, primary chicken
      embryo fibroblast (CEF) cells, or embryonating chicken eggs (embryos) or one time
      in the bursa of Fabricius (BF) of specific-pathogen-free (SPF) chickens. Passage
      in BGM-70 cells or CEF cells resulted in loss of pathogenicity, but viruses
      passaged in embryos or BF maintained their pathogenicity. For the immunogenicity
      study, the viruses described above were used to prepare live and inactivated
      vaccines, containing 10(3) mean embryo infectious doses (EID50s) and 10(5) EID50s
      respectively. These vaccines induced different levels of protection. It was
      concluded that the antigen titration methodology employing embryonating chicken
      eggs was not suitable for titration of viruses propagated in other host systems
      because of varying degrees of adaptation and/or pathogenicity of the viruses
      resulting in variability in antigen mass of the tested vaccines. To test this
      assumption, an antigen-capture enzyme-linked immunosorbent assay was used as a
      titration system to compare the antigenicity of viruses propagated in BGM-70
      cells or BF. Preparations containing similar antigen masses were inactivated then
      inoculated into two age groups of SPF chickens and antibody titers were
      monitored. During the experimental period, the geometric mean virus-neutralizing
      (VN) antibody titers of the vaccinated groups did not differ significantly (P >
      0.05).

PMID- 8883784
TI  - Comparison between antigen-capture ELISA and conventional methods used for
      titration of infectious bursal disease virus.
AB  - Two antigen-capture enzyme-linked immunosorbent assays (polyclonal and monoclonal
      AC-ELISAs) were developed and evaluated for titration of infectious bursal
      disease viruses (IBDVs) propagated in different host systems, namely BGM-70
      continuous cell line, primary chicken embryo fibroblast cells, and chicken bursa
      of Fabricius. The polyclonal system was more sensitive (P < 0.05) than the
      monoclonal system but both were specific as indicated by the negative results
      obtained with three non-IBDVs. The results revealed that the conventional systems
      used for titration of IBDVs (cell cultures and embryonating chicken eggs) were
      more sensitive than the polyclonal AC-ELISA.

PMID- 8883785
TI  - Pathogenicity, attenuation, and immunogenicity of infectious bursal disease
      virus.
AB  - An investigation was conducted in specific-pathogen-free chickens on the
      pathogenicity of bursa-derived and tissue culture-attenuated classic (STC) and
      variant (IN) serotype 1 strains of infectious bursal disease virus. The IN bursa
      derived virus caused bursal inflammation, necrosis, and atrophy earlier than the
      bursa-derived STC virus. Both viruses lost their pathogenicity after four
      passages in BGM-70 cells. A statistically significant level (P < 0.05) of
      protection was observed in SPF chickens vaccinated with the attenuated IN virus
      used as a live or inactivated vaccine followed by homologous (IN) and
      heterologous (STC) challenge with bursa-derived viruses.

PMID- 8883786
TI  - Respiratory coccidiosis (Cryptosporidium baileyi) among northern Georgia broilers
      in one company.
AB  - Cryptosporidium baileyi causes respiratory disease in chickens. The purposes of
      this prospective study were to determine the incidence of C. baileyi tracheitis
      among broilers in a commercial setting, and the relationship between C. baileyi
      tracheitis and production performance parameters. All samples came from 56 farms
      that grow broilers for one company in northern Georgia. Tracheas were collected
      and examined with a light microscope and cultured for viruses and bacteria.
      Overall, 23 of 56 (41%) broiler flocks had C. baileyi tracheitis. Parasitism
      rates among C. baileyi-infected flocks ranged from a low of 10% to a high of 60%.
      Cryptosporidium baileyi tracheitis was very highly correlated (rho = 0.81, n =
      56, P < 0.00001) to severity of tracheitis, negatively correlated (rho = -0.27, n
      = 56, P < 0.04) with average body weight, and correlated with airsacculitis (rho
      = 0.30, n = 56, P < 0.03) and condemnations (rho = 0.27, n = 56, P < 0.05). The
      present study indicates that C. baileyi infection rates are high, and the role
      that this parasite plays in the pathogenesis of respiratory disease and
      production losses could be unexpectedly large.

PMID- 8883787
TI  - Genetic susceptibility to Marek's disease virus of local chickens in Taiwan.
AB  - Marek's disease is a contagious disease in chickens caused by Marek's disease
      virus (MDV) infection. Invasion of very virulent MDV (vvMDV) was considered to be
      a major cause of vaccine break, resulting in a large economic loss in the poultry
      industry. Two strains of the vvMDV (strains LTB-1 and LTS-1) have been reported
      in Taiwan, causing early mortality and formation of lymphoid tumors in broilers
      and layers. In this study, we report the susceptibility of local chickens in
      Taiwan to inoculation with strains LTB-1 and LTS-1 at 1 day of age. Five lines of
      Taiwanese local chickens (lines B, D, L2, KM, and BG) were used to compare the
      susceptibility to vvMDV. The chicks were inoculated via intraperitoneal route at
      1 day of age. All MDV-inoculated chickens showed atrophy of various lymphoid
      organs. Protection tests were also conducted in local chickens, using vaccine of
      herpesvirus of turkey (HVT) at 1 day of age followed by vvMDV challenge at 10
      days of age. Among the vaccinated chickens, 0-20.0% showed early mortality, and
      tumor occurrences in visceral organs and in peripheral nerves were 66.7%-100% and
      0-27.2%, respectively. From these results, it could be concluded that local
      chickens in Taiwan have different susceptibilities to vvMDVs. Furthermore,
      vaccination with HVT showed no protective effect against Taiwanese vvMDV isolate
      challenge in this experiment.

PMID- 8883788
TI  - Evaluation of a commercial modified live virus fowl pox vaccine for the control
      of "variant" fowl poxvirus infections.
AB  - Three-week-old specific-pathogen-free chickens were vaccinated with either a
      commercial modified live virus fowl pox vaccine or five "variant" poxvirus field
      isolates. Immunity engendered by the commercial modified vaccine or field
      isolates was challenged with either the variant isolates or commercial modified
      vaccine virus. The commercial modified vaccine did not adequately protect
      vaccinates against challenge with the variant isolates. The percentages of
      vaccinated chickens protected following challenge with each of the variant
      isolates were 70%, 20%, 30%, 20%, and 25%. However, when the isolates were
      applied as vaccines, 100% of the vaccinates were protected against challenge from
      the modified vaccine virus. Furthermore, the variant poxvirus isolates offered
      excellent protection from challenge with homologous variant isolates. The
      modified live virus vaccine was expected to offer significant protection against
      challenge from the variant pox isolates, but in this experiment it did not. The
      variant isolates tested may be good vaccine candidates to prevent the vaccine
      breaks currently encountered in previously pox-vaccinated flocks.

PMID- 8883789
TI  - Antigenic characterization of an Arkansas isolate of infectious bursal disease
      virus.
AB  - The s977 strain of infectious bursal disease virus (IBDV) was isolated in
      northwest Arkansas in 1977 from the bursae of young broilers with high maternal
      antibody titers to the Moulthrop strain of IBDV (BursaVac). The comparison of a
      plaque-purified isolate of s977 with other IBDV serotype 1 and serotype 2 strains
      using virus neutralization indicates that s977 is a subtype of serotype 1 vaccine
      viruses and the MD variant strain of IBDV and has no relatedness to the Delaware
      Variant A (VarA) virus. In vivo cross-protection studies in specific-pathogen
      free white leghorn chickens showed that an inactivated vaccine using s977 antigen
      was 2.5 times more protective against challenge with s977 than was an inactivated
      IBDV Variant E (VarE) vaccine. The vaccination of maternally immune broiler
      chicks with live s977 did not provide protection against subsequent challenge,
      indicating that s977 does not have enough antigenic difference to break through
      maternal immunity. Analysis of denatured viral polypeptides using polyacrylamide
      gel electrophoresis showed that s977 and two reported variant strains, 51 and
      VarE, share three protein bands, 90 kD (VP1), 40 kD (VP2), and 31 kD (VP3), that
      were not observed in BursaVac. BursaVac and s977 shared a 74 kD precursor band
      that was absent or very faint in the VarE and 51 strains. The most unique
      characteristic of s977 was the relative abundance of a wide, 56-63 kD band that
      contained two distinct immunoreactive bands when blotted with antiserum to s977.
      BursaVac contained a 56 kD band that failed to react with s977 antiserum.
      Analysis of polypeptide bands using laser densitometry indicated the presence of
      a number of bands between 20 kD and 25 kD in the s977, 51, and VarE preparations
      but only a 25 kD band in BursaVac. The number of bands decreased with the degree
      of relatedness to standard vaccine strains. It appears that, antigenically, S977
      may hold an intermediate position between the classic virus strains and the more
      recently reported serotype 1 variants.

PMID- 8883790
TI  - Susceptibility of pigeons to avian influenza.
AB  - Susceptibility to infection with avian influenza virus (AIV) was studied in
      pigeons inoculated via oculonasal (Experiment 1) or intravenous (Experiment 2)
      route. Chickens were included as susceptible hosts in both experiments. Two
      subtypes each of the highly pathogenic AIV (HPAIV; HP CK/PA H5N2 and HP
      CK/Australia H7N7) and non-pathogenic AIV (NPAIV; NP CK/PA H5N2 and NP emu/TX
      H7N1) at a dose of 10(5) embryo infective dose per bird were used as inoculum.
      The pigeons inoculated with HP CK/PA H5N2 or HP CK/Australia H7N7 remained
      apparently healthy throughout the 21-day observation period, did not shed viruses
      on 3, 7, 14, and 21 days postinoculation (DPI), and had no demonstrable levels of
      antibodies on 21 DPI. On the other hand, 9 of 12 chickens inoculated with the
      HPAIV died of highly pathogenic avian influenza; the viruses were recovered from
      their respiratory and intestinal tissues, and the surviving chickens had
      antibodies to AIV. Regarding responses of pigeons to inoculation with NP CK/PA
      H5N2 or NP emu/TX H7N1, the pigeons remained clinically healthy throughout the 21
      day observation period and did not have detectable levels of antibodies on 21
      DPI; only one pigeon yielded the NP emu/TX H7N1 on 3 DPI. The virus was isolated
      from a tracheal swab and was believed to be the residual inoculum virus. Based on
      the responses of pigeons to NPAIV and HPAIV, it was concluded that the pigeons
      were resistant or minimally susceptible to infection with HPAIV or NPAIV.

PMID- 8883791
TI  - Attenuation of lentogenic Newcastle disease virus strain B-1 by cold adaptation.
AB  - The Hitchner B-1 strain of Newcastle disease virus was plaque-cloned and then
      serially passaged 36 times in specific-pathogen-free (SPF) chicken embryos
      incubated at two different temperatures. Virus passaged at a reduced temperature
      (29 C) was identified as cold-adapted (Ca) and virus passaged at the normal
      temperature (37 C) was designated non-cold-adapted (non-Ca). The Ca and non-Ca B
      1 viruses were compared with the parent B-1 and a commercial B-1 vaccine. In
      vitro Ca B-1 characteristics included adaptation for more rapid growth at 29 C
      and the aquisition of temperature sensitivity indicated by substantially reduced
      growth at 41 C, properties not seen with non-Ca B-1. Embryo mean death times for
      the Ca virus (140 hr) were longer than for non-Ca B-1 (107 hr) and parent B-1
      (121 hr) viruses. The Ca virus retained a rapid (< 2 hr) hemagglutination (HA)
      elution rate but lost the property of binding the monoclonal antibody AVS-I
      typical of other B-1 strains. The pathogenicity of the Ca B-1 strain was compared
      to the non-Ca B-1, parent B-1 strain, and a commercial B-1 strain vaccine in 1
      day-old broiler-type chickens. Pathogenicity was evaluated by assessing the
      severity of respiratory disease signs and the incidence of airsacculitis,
      perihepatitis, and pericarditis lesions in inoculated chicks. A respiratory
      disease index was calculated for each B-1 strain based on daily observation
      scores that determined the presence or absence of disease signs (coughing, rales,
      labored breathing, death) from 1 to 14 days following intratracheal inoculation
      with 10(6) 50% egg infective doses of virus per chick. The lower respiratory
      disease index obtained for the Ca B-1 strain (0.075) indicated it was less
      pathogenic than the commercial B-1 vaccine (0.296) and the non-Ca (0.478) and
      parent (0.521) B-1 strains. Ca B-1-infected chicks had only a 5% incidence of air
      sac lesions, compared to chicks given non-Ca (65%), Hitchner B-1 (65%), or a
      commercial B-1 vaccine (30%). Immunogenicity tests performed in 1-week-old SPF
      leghorn chickens demonstrated that Ca B-1 induced complete protection when
      administered intraocularly as a single entity. However, when Ca B-1 was given in
      combination with a modified live infectious bronchitis virus vaccine, chickens
      were only partially protected (60-75%) against Texas GB strain-induced
      neurotropic velogenic Newcastle disease.

PMID- 8883792
TI  - Monoclonal antibodies specific to Mycoplasma iowae.
AB  - Monoclonal antibodies (MAbs) against Mycoplasma iowae (MI) were produced to
      identify common immunogenic determinants shared between antigenically
      heterogenous MI. Twenty-four MAbs were produced against MI. With western
      immunoblotting, all 24 MAbs recognized a 45,000-MW protein (p45) of MI strain I
      695. One of the MAbs characterized, MAb 2C, identified p45 antigen in western
      immunoblots with six laboratory strains and 24 field isolates of MI. MAb 2C did
      not cross-react with Mycoplasma gallisepticum, Mycoplasma synoviae, Mycoplasma
      meleagridis, or nonpathogenic avian mycoplasmas. Triton X-114 phase separation of
      MI proteins showed that p45 is an integral membrane protein. In immunofluorescent
      staining and immunoelectron microscopy of MI, MAb 2C reacted with surface
      antigen(s). These MAbs specific to MI may be used in detection and diagnosis of
      MI infections.

PMID- 8883793
TI  - Isolation, pathogenicity, and H120 protection efficacy of infectious bronchitis
      viruses isolated in Taiwan.
AB  - Seven isolates of infectious bronchitis (IB) virus (IBV) were isolated from two
      breeder farms and five broiler farms in Taiwan in 1992. The cardinal signs of
      disease in breeders were egg production drops and watery albumen, and those in
      broilers were respiratory distress and renal urate deposition or death. All
      diseased chickens had been vaccinated with IB vaccines (mostly H120). The viruses
      were isolated and identified by chicken embryo inoculation and electron
      microscopy. The genomes of the isolates were extracted and amplified by
      polymerase chain reaction; the restriction fragment length polymorphism analysis
      suggested that the genotypes of the present IBV isolates were different from the
      eight reference strains. One-day-old specific-pathogen-free chicks were
      inoculated with the field isolates in order to test the virulence of those
      isolates. Respiratory distress and depression commenced at 24 hours after
      inoculation. Two of the seven isolates were found to be highly virulent, causing
      50% or more mortality in inoculated chicks. Vaccine protection tests showed that
      H120 could protect chickens against challenges with four of six field isolates.

PMID- 8883794
TI  - Studies of contamination of three broiler breeder houses with Salmonella
      enteritidis before and after cleansing and disinfection.
AB  - Three broiler breeder houses on three different sites were sampled before and
      after cleansing and disinfection. None of the farms achieved total elimination of
      Salmonella enteritidis from the poultry house environment but substantial
      improvements were seen when errors in the cleansing and disinfection protocol in
      the first house had been corrected. Fundamental errors such as over-dilution and
      inconsistent application of disinfectants were observed despite supervision of
      the process by technical advisors. In each of the three poultry units failure to
      eliminate a mouse population that was infected with S. enteritidis was likely to
      be the most important hazard for the next flock.

PMID- 8883795
TI  - Divergent antibody responses to vaccines and divergent body weights of chicken
      lines selected for high and low humoral responsiveness to sheep red blood cells.
AB  - Primary and secondary antibody responses to intramuscularly administered proteins
      of Eschericia coli (F11), Newcastle disease virus (NCD), infectious bronchitis
      virus (IB), and infectious bursal disease virus (IBD), respectively, were
      measured at weekly intervals in two chicken lines. The latter had been
      divergently selected for high and low antibody responses to sheep red blood cells
      (SRBC), and in a random-bred control line. An oil-based adjuvant was required to
      induce primary and secondary antibody responses to NCD, IB, and IBD. With respect
      to F11, elevated antibody responses were found in birds sensitized and boosted to
      F11 with and without adjuvant. The humoral response to F11 and to all viral
      antigens was significantly higher in the high (H) line than in the low (L) line,
      whereas the control (C) line showed intermediate titers. At 5 and 17 weeks of
      age, L line birds were significantly heavier than birds of the H and the C lines.
      A negative phenotypic correlation within lines between body weight at 17 weeks of
      age and antibody titers at 1 week after sensitization was found, but no further
      correlations between humoral responses and body weight or growth could be
      established. The present results suggest that selection for enhanced humoral
      responsiveness to SRBC resulted in enhanced responsiveness to components of
      several vaccines. Mechanisms underlying the relationship between divergent
      selection for immune responsiveness and body weight are discussed.

PMID- 8883796
TI  - Influence of Marek's disease virus strain AC-1 on cellular immunity in birds
      carrying endogenous viral genes.
AB  - The effects of Marek's disease virus (MDV) strain AC-1 on humoral and cellular
      immune responses were investigated in two lines of chickens segregating for the
      endogenous viral (ev) genes ev-6 and ev-12. All birds were vaccinated at 14 days
      of age against Newcastle disease virus (NDV). At 3 wk of age, 48 birds per line
      received an intraperitoneal injection of MDV (AC-1 isolate), and 24 were injected
      with saline. Birds of each group were killed on days 5, 7, 12, and 14
      postinfection. Data were first analyzed for each day of testing. Results showed
      that, for variable measured, treatment effects were similar on days 5 and 7, and
      on days 12 and 14. Therefore, day 5 and day 7 data, and day 12 and day 14 data
      were pooled and analyzed. In MDV-infected chickens, proliferative lymphocyte
      responses to mitogens were suppressed (P < 0.001) after the first and second week
      of infection, whereas responses to NDV antigen were enhanced (P < 0.001) after
      the first week and then reduced (P < 0.01) by the end of the second week when
      compared to uninfected birds. The percentage of CD4+ T cells was higher (P <
      0.01), and the percentage of cells expressing major histocompatibility complex
      (MHC) class II antigens was lower (P < 0.001), in MDV-infected chickens than in
      uninfected birds. The cytotoxic activity of natural killer (NK) cells was also
      enhanced (P < 0.001) in MDV-infected birds when compared to uninfected birds.
      Antibody responses to NDV were not different among groups, and the presence of ev
      6 or ev-12 genes did not influence the immune response parameters measured in
      both infected and uninfected chickens. In conclusion, a marked increase in the
      CD4+ T lymphocyte population occurred in the early stage of MDV infection in all
      chickens regardless of the presence of ev genes, whereas the number of cells
      expressing MHC class II antigen was severely reduced.

PMID- 8883797
TI  - Standardized method of aerosol challenge for testing the efficacy of Mycoplasma
      gallisepticum vaccines.
AB  - A special chamber was constructed with the goal of controlling the process of
      aerosol infection of chickens with Mycoplasma gallisepticum (MG). The virulent
      Australian MG field strain Ap3AS was used in each of three experiments. The
      response to infection of layer-strain pullets was measured serologically, by the
      incidence and severity of gross lesions in tracheas and air sacs, and by the
      relative numbers of MG isolated from tracheas and air sacs 2 wk after challenge.
      In two of the experiments tracheal sections were assessed microscopically.
      Exposure to a nebulized, undiluted broth culture of MG for 10, 20, or 30 min
      produced uniformly severe lesions and serological responses. By contrast, results
      were less severe and less consistent when doses of up to 10(8) color-changing
      units (CCU) were injected directly into the abdominal air sacs. Gross air sac
      lesions were consistently produced in almost all pullets by exposure to an
      infectious aerosol containing 10(2)-10(3) CCU/liter of air for 10 min and an air
      flow rate of 40 liters/min. This can be achieved by nebulizing a 10(-3) dilution
      of a fresh, early stationary phase culture of MG strain Ap3AS. However, under the
      conditions of these experiments, this dose did not produce significant gross or
      histologic lesions in the trachea.

PMID- 8883798
TI  - Distribution of arthritis and osteomyelitis in turkeys with green liver
      discoloration.
AB  - The distribution of arthritis and osteomyelitis (OM) was studied in turkeys with
      green liver (GL) discoloration collected in a processing plant; the turkeys
      originated from seven commercial farms. Overall occurrence of GL, arthritis, and
      OM in the 25,320 inspected toms was 264 (1.04%), 123 (0.49%), and 107 (0.42%),
      respectively, and in the 16,690 inspected hens was 24 (0.14%), 0%, and 13
      (0.08%), respectively. Prevalence of GL, OM, and arthritis varied among the
      studied farms. Arthritis and/or OM were detected in 168 (58.3%) of 288 turkeys
      with green discolored livers. Of the 168 turkeys with OM and/or arthritis, 48
      (28.6%) had only arthritis, 45 (26.8%) had OM only, and 75 (44.6%) had both
      lesions. Arthritis and OM were detected in single and multiple sites and were
      unilateral and bilateral. Distribution of OM in the 120 OM-positive turkeys with
      and without arthritis was 77 (64.2%) in proximal tibia, 29 (24.2%) in proximal
      humerus, 28 (23.3%) in proximal femur, 13 (10.8%) in rib cage, and 4 (3.3%) in
      distal femur. Distribution of arthritis in the 123 arthritis-positive turkeys
      with and without OM was 77 (62.6%) in shoulder, 45 (36.6%) in stifle, and 25
      (20.3%) in hip joints. Findings in this study suggest that arthritis and
      osteomyelitis are two distinct lesions and that they may develop independently in
      the same bird.

PMID- 8883799
TI  - Salmonella enteritidis, phase type 4 infection in a commercial layer flock in
      southern California: bacteriologic and epidemiologic findings.
AB  - Salmonella enteritidis, phage type 4 (SE PT4), was isolated from five of six 27
      wk-old layer chickens submitted for necropsy from a flock of 43,000.
      Bacteriologic and epidemiologic investigations on the ranch revealed that five of
      the eight flocks (n = 176,000) were infected. The prevalence of SE PT4 in
      randomly selected healthy birds ranged from 1.7% (in caged birds) to 50% (in free
      range birds) and prevalence in culled birds (kept on dirt floor houses) ranged
      from 14% to 42%. The estimated overall prevalence of group D Salmonella in eggs
      contaminated with group D Salmonella was 2.28 per 10,000. The estimated
      prevalence of group D Salmonella in eggs from caged birds in three infected
      houses ranged from 1.5 to 4.1 per 10,000, whereas in two houses of free-range
      birds, prevalence was 14.9 to 19.1 per 10,000. Three of the eight flocks on the
      ranch remained negative for Salmonella between May 1994 and December 1995 or
      until removed from the ranch. Salmonella enteritidis PT4 was also isolated from
      12.5% (6 of 48) of mice; 57% (four of seven) of cats; and two of two skunks
      tested. Environmental drag swabs and well water samples yielded multiple
      serotypes of Salmonella (23/180 and 5/14, respectively) but not S. enteritidis.

PMID- 8883800
TI  - Sewage effluent: likely source of Salmonella enteritidis, phage type 4 infection
      in a commercial chicken layer flock in southern California.
AB  - Following the diagnosis of Salmonella enteritidis, phage type 4, infection in a
      commercial layer flock in southern California, effluent from a nearby sewer
      treatment plant was investigated as a potential source of infection. Between July
      1994 and March 1995, 68 Salmonella isolations, comprising 27 serotypes, were made
      from the inflow (raw sewage) and effluent (treated sewage). Thirty-nine of 68
      (57%) isolations yielded six serotypes, which consisted of S. enteritidis 12%
      (8/68), S. cerro 10% (7/68), S. typhimurium 7.4% (5/68), S. tennessee 7.4%
      (5/68), S. give 7.4% (5/68), S. mbandaka 7.4% (5/68), and S. panama 6% (4/68).
      The remaining 43% (29/68) isolations were represented by 21 serotypes. Seventeen
      S. enteritidis isolates originating from the effluent (creek water), resident
      feral animals (rodents, stray cats, skunks), and chickens (organs, eggs) of the
      affected flock were subjected to plasmid profile and restriction endonuclease
      analysis. Twelve of the 17 isolates had identical plasmid profile and restriction
      digestion patterns. Two of 17 isolates showed similar patterns but both differed
      from the rest; and 1 of 17 did not yield plasmids. Two other isolates were found
      to be different from each other and from the rest of the group.

PMID- 8883801
TI  - A prospective study of cellulitis in broiler chickens in southern Ontario.
AB  - This study investigated the associations among cellulitis and hatchery, farm, and
      abattoir factors. Forty-four broiler flocks from 24 farms located in southern
      Ontario were followed from hatching to processing. Poisson regression was used to
      analyze the data. Cellulitis as a count outcome (CELLCOUNT) was significantly
      associated (P < or = 0.05) with the hatchery of origin, strain of birds, farm
      size, type of litter, lighting system, total down time, prevalence of abdominal
      scratches, Escherichia coli-related conditions (SEROSITIS), ascites, and valgus
      varus deformity. However, only farm size, abdominal scratches, SEROSITIS,
      ascites, and valgus varus deformity were significant (P < or = 0.05) after
      adjusting for clustering. No significant associations were found between
      cellulitis and source of eggs, sex, average bird weight, feed company, growth
      promoter, or stocking density. Factors significantly associated with cellulitis
      in this study could be considered as potential risk factors for cellulitis in
      broiler chickens in southern Ontario.

PMID- 8883802
TI  - Description of cellulitis lesions and associations between cellulitis and other
      categories of condemnation.
AB  - A total of 110 broiler flocks processed in a single processing plant in southern
      Ontario were studied for purposes of describing the cellulitis lesions and
      investigating possible associations between cellulitis and other categories of
      condemnation at the processing plant. Two hundred and ninety-five carcasses
      condemned for cellulitis were examined. They came from 65 of the 110 flocks. The
      lesions tended to be unilateral with most carcasses (87%) having one lesion. The
      majority of the lesions (92%) were located on the abdomen. Almost 65% of the
      lesions were large (> or = 8.1 cm2), and 27% were medium (2.1-8.0 cm2). On the
      basis of gross appearance, 69% of the lesions were classified as severe, 26%
      moderate, and 5% mild. Of 149 lesions examined histologically, 74% were
      classified as chronic, 21% ongoing, and 5% mild-acute. Condemnation data from the
      110 broiler flocks were analyzed using Poisson regression. Simple relationships
      were examined between a count outcome (number of cellulitis-condemned carcasses
      per flock) and other categories of condemnation and average bird weight.
      Cellulitis was significantly associated with average bird weight (P = 0.0018),
      Escherichia coli-related conditions (SEROSITIS; P < or = 0.0001), ascites (P =
      0.0004), cyanosis (P < or = 0.0001), valgus varus deformity (P < or = 0.0001),
      REJECT (combined carcass condemnations for bruising, mutilation, and
      contamination; P = 0.0003), and the interaction terms "average bird weight and
      ascites" (AVWT*ASCIT; P < or = 0.0001) and "average bird weight and cyanosis"
      (AVWT*CYAN; P < or = 0.0001). Average bird weight, SEROSITIS, ascites, cyanosis,
      valgus varus deformity, and AVWT*ASCIT were the only significant factors after
      adjusting for clustering. No association was observed between cellulitis and
      emaciation and dead on arrival. Variables significantly associated with
      cellulitis in the multivariate analysis could be considered as potential
      predictors. These predictors may share common risk factors predisposing broiler
      chickens to cellulitis.

PMID- 8883803
TI  - Farm management risk factors associated with cellulitis in broiler chickens in
      southern Ontario.
AB  - A mail survey of 171 farms with broiler chicken flocks processed in a single
      processing plant in southern Ontario was conducted during the period July-August
      1993 as part of a retrospective study. The population farm prevalence of
      cellulitis was 31/10,000 birds. The survey provided information about the
      management of broiler chickens in southern Ontario and allowed investigation of
      the association between cellulitis and management risk factors. Univariate and
      multivariate analyses were performed to examine the relationship between a binary
      outcome (high/low prevalence) and management risk factors using logistic
      regression. Cellulitis was positively associated (P < or = 0.05) with male and
      mixed (males and females) flocks, use of straw as litter, certain feed companies,
      use of zinc bacitracin as a growth promoter, and other diseases diagnosed at the
      processing plant. Total down time was negatively associated with cellulitis.

PMID- 8883804
TI  - Avian paramyxovirus type 1 from pigeons: isolate characterization and
      pathogenicity after chicken or embryo passage of selected isolates.
AB  - Nine pigeon paramyxovirus type 1 isolates from the United States and Canada were
      characterized and three of the isolates were pathotyped before and after passage
      in chickens and serial passage in chicken embryos. One isolate previously
      passaged in Madin Darby bovine kidney cells was also pathotyped after chicken and
      embryo passage. Hemagglutination (HA) titers of all isolates were low when tested
      by microtiter procedures and all were negative by rapid-plate HA. The HA titers
      were increased by a factor of 8 to 32 by Tween-ether treatment, and treated
      antigen had the same reactivity as untreated antigen in hemagglutination
      inhibition (HI) tests. All isolates had a slow elution rate and an HA
      thermostability equal to or greater than 60 minutes. Mean death times in embryos
      were 99 hours or greater, except for one isolate with a mean death time of 81
      hours, and intracerebral pathogenicity indices of all isolates were greater than
      1. Antigenic differences among the pigeon isolates were identified by three
      different binding patterns in HI tests against a battery of five Newcastle
      disease virus (NDV) monoclonal antibodies. Pathogenicity enhancement by bird,
      embryo, or cell passage was limited to an intravenous pathogenicity index
      increase for one of three viruses passaged in embryonated eggs. Cloacal samples
      collected during chicken passage contained higher virus titers than did oral
      samples. The pigeon isolates reported here, like those of earlier reports, have
      properties that prevent characterization within a single NDV pathotype. Finally,
      there was no evidence that any of these isolates was highly virulent for
      chickens.

PMID- 8883805
TI  - Elevated plasma glycosaminoglycans in chickens with tibial dyschondroplasia
      induced by a Fusarium oxysporum isolate.
AB  - Chicken plasma glycosaminoglycans (GAGs) were isolated and digested. Their
      building block molecules, namely, glucosamine and galactosamine, were quantified
      by gas chromatography. The levels of these two amino sugars were elevated in
      broiler chickens with tibial dyschondroplasia (TD) induced by culture material of
      Fusarium oxysporum (FO), a mold isolated from corn originated from the endemic
      region of Kaschin-Beck disease (KBD) in China. As the TD severity score changed
      from 1 (healthy) to 2, 3, and 4, glucosamine increased by 10%, 33%, and 57% and
      galactosamine by 9%, 13% and 48%, respectively. The elevated plasma GAGs
      correlated to TD severity but not to the amount of FO material in the diets. This
      correlation of plasma GAGs to TD in chickens parallels the reported correlation
      of urinary GAGs to KBD in humans. The possibility of TD as an animal model for
      KBD is discussed.

PMID- 8883806
TI  - Hepatic and renal ultrastructural lesions in experimental Clostridium perfringens
      type A enterotoxemia in chickens.
AB  - Hepatic and renal electron microscopic investigations were carried out in 10
      chickens that had experimental intraduodenal infection with Clostridium
      perfringens Type A. Fourteen days postinfection, there were ultrastructural
      changes in hepatocytes and renal tubular epithelial cells; these included
      mitochondrial lesions (swelling, cristolysis, rarefication of the matrix, myelin
      figures), glycogen loss, and capillary endothelial cell swelling in both organs,
      as well as thickening of glomerular basement membrane. The findings are discussed
      with particular reference to the pathogenesis of Clostridium perfringens Type A
      enterotoxemia.

PMID- 8883807
TI  - Pathogenicity of three avian influenza viruses for Leghorn hens of different
      ages.
AB  - Pronounced host effects on clinical responses to influenza virus infection were
      not observed in any of seven trials in which young (26-43 weeks) and olf (65-94
      weeks) leghorn hens were inoculated with low pathogenic subtype H5N2, H4N8, or
      H3N2 virus. In two of seven trials, where hens were infected with H4N8 or H3N2
      virus, morbidity rates were slightly higher for old hens than for young hens.
      These observations indicate that host age effects of the severity of
      uncomplicated influenza virus infections are likely to be minimal in sexually
      mature chickens.

PMID- 8883808
TI  - Modification of a technique for support of thin, flexible tissues for microscopic
      examination: application to turkey air sac membranes.
AB  - Modifications to the ring-stabilization technique for collection of avian air sac
      membranes were developed to allow dehydration and paraffin embedding of samples
      to be done by an automated system and to simplify processing for transmission
      electron microscopy (TEM). The modified collection method utilized a pair of
      rings that were snapped together across an intervening membrane sample. The
      tissue and ring ensemble was embedded as a unit. Paraffin-embedded tissues were
      collected with aluminum rings, whereas samples for TEM were collected with rings
      made of polymerized embedding medium. Tissue sections of excellent quality were
      obtained with the method. The technique is shown to be applicable to
      immunohistochemical studies.

PMID- 8883809
TI  - Excessive mortality in market-age turkeys associated with cellulitis.
AB  - Between July, 1993, and October, 1994, seven cases were examined that consisted
      of increased mortality in commercial turkeys due to cellulitis. The condition
      started at 13-16 wk of age in toms and persisted until the birds were marketed.
      The mortality rate was 1-2% per week. Lesions began on the ventrum of the tail
      and consisted of swelling and the formation of vesiclelike structures. Most of
      the affected birds also had an accumulation of gelatinous fluid in the subcutis
      of the tail and breast areas. The underlying musculature was often darkened or
      petechiated. Clostridium perfringens type A was isolated from two of the cases.
      Lesions similar to those found in the field were reproduced experimentally in
      turkeys injected with the subcutaneous fluid obtained from birds in field cases.

PMID- 8883810
TI  - Two outbreaks of colibacillosis in commercial caged layers.
AB  - A severe septicemia of Escherichia coli etiology was diagnosed in two houses
      containing 51,570 and 76,200 layers with mortalities of 6.83% and 4.27%,
      respectively. Dead birds were removed every other day; however, on occasion,
      gathering was done on the third day. The disease started in 22-wk-old pullets,
      and 3 wk later was diagnosed in 82-wk-old birds in an adjoining house. The
      duration of mortality in house 1 was 12 wk and in house 2 was 13 wk. A non
      lactose-fermenting E. coli was isolated. Another outbreak of colibacillosis was
      diagnosed with 7.8% mortality at a different farm containing 47,000 110-wk-old
      hens and 10,000 40-wk-old pullets. On this farm the duration of mortality was not
      provided. Antibiotic treatment failed to reduce losses; chlorine added to the
      drinking water was effective in controlling the spread of disease and in reducing
      mortality at both farms.

PMID- 8883811
TI  - Recovery from early cortical damage in rats, VII. Comparison of the behavioural
      and anatomical effects of medial prefrontal lesions at different ages of neural
      maturation.
AB  - Rats with removal of the medial prefrontal (mPFC) cortex at days 3, 6, 9, 15, or
      30 were compared behaviourally and anatomically to littermate controls. In
      contrast to adult operates, mPFC lesions at all young ages led to the development
      of an abnormally thin cortical mantle. In addition, although there was an obvious
      cavity in brains examined in the early postoperative period, the brains of
      animals with lesions at day 9 or 15 had no lesion cavity in adulthood as part of
      the cortex appeared to regrow. The differential anatomical consequences of the
      lesions at days 9 and 15 was correlated with a differential behavioural outcome
      as well. Thus although rats in all young lesion groups showed a milder
      behavioural syndrome than rats with comparable lesions in adulthood, the
      functional outcome was best for animals with lesions at 9 days of age.

PMID- 8883812
TI  - No sex difference occurs in hippocampus, food-storing, or memory for food caches
      in black-capped chickadees.
AB  - A number of recent studies have described sex differences in the relative size of
      the hippocampus that are associated with sex differences in the use of space.
      Voles, kangaroo rats, and cowbirds all exhibit a sex difference in relative size
      of the hippocampal formation that is correlated with a sex difference in spatial
      behaviour. We wished to determine whether sex differences in the size of the
      hippocampus occur in the absence of a difference in the use of space, and whether
      the previously described correlations could be adventitious. Relative hippocampal
      size was determined in wild-caught black-capped chickadees (Parus atricapillus)
      following behavioural observations of food caching and spatial memory for cache
      sites. There was no indication of a sex difference in either relative size of the
      hippocampus or in food-caching behaviour and memory for cache sites. These
      results show that sex differences in relative size of the hippocampus do not
      occur as a matter of course, and are consistent with the hypothesis that sex
      differences in spatial behaviour and spatial ability are predictive of sex
      differences in the relative size of the hippocampus.

PMID- 8883813
TI  - Dopamine and opioid regulation of the memory retrieval recovery in mice.
AB  - The reactivation effects of the delta-opioid receptor blockade and D2 dopamine
      receptor activation on the detention-induced memory deficit in mice were
      investigated, in order to study possible interactions between opioid and dopamine
      systems in memory retrieval. Animals were trained in a one-trial passive
      avoidance task. Pretesting treatment with ICI 174,864 (1, 3 or 5 mg/kg, i.p.) or
      quinpirole (0.5, 1 or 2 mg/kg, i.p.) facilitated retrieval of memory trace in
      saline-pretreated mice. Pretraining injection of the dopamine autoreceptor
      agonist, (+)-3PPP (2 mg/kg), having no effect alone in learning, prevented the
      ability of ICI 174,864 to produce the memory-enhancing effect. It is suggested
      that the normal functioning of the dopamine system was critical for the
      facilitation of retrieval by delta-antagonist. Quinpirole-induced reactivation of
      memory retrieval was enhanced by pretreatment with Leu-enkephalin (0.2 mg/kg),
      inducing increased retention. We discuss these results in the context of an
      important interactions between D2 dopamine and delta-opioid receptors.

PMID- 8883814
TI  - Effect of lesioning the nucleus accumbens on attentive preparation and
      performance of a reaching movement in the cat.
AB  - The nucleus accumbens is often considered as an interface between limbic and
      motor brain structures. In the present experiment, we investigated the effect of
      a bilateral lesion of the nucleus accumbens on a motor task with attentional
      constraints. Four male cats were trained to reach for a mobile target that was
      only accessible for a short period of time and after a variable delay of
      expectation. They were food-rewarded. Their visuomotor performance was analyzed
      in speed and accuracy. Their ECoG was recorded to evaluate the occurrence of beta
      rhythms that have been shown to be related to a behaviour of focalized attention.
      After stabilization of their visuomotor performance, all subjects underwent a
      bilateral neurotoxic lesion of the nucleus accumbens. After lesion, cats were
      able to maintain their focalized attention while waiting for the target for
      longer periods of time and the probability of beta-activity increased. Their
      visuomotor performance showed an improvement both in accuracy and in speed.
      Moreover, unexpected external stimuli were less efficient in diverting the cats'
      attention from their task, so that the proportion of unsuccessful trials due to
      inattention decreased after lesion. The data showed that the lesion induced a
      focalization of attention resulting in an improvement of motor performance. The
      role of the nucleus accumbens both in attention control and in modulating motor
      output is discussed together with the possible cerebral pathway involved.

PMID- 8883815
TI  - Apomorphine produces an acute dose-dependent therapeutic effect on neglect
      produced by unilateral destruction of the posterior parietal cortex in rats.
AB  - The neglect syndrome is a complex and devastating neurological disorder typically
      induced by unilateral destruction of one of three regions of the neocortex: the
      inferior parietal lobule, the dorsolateral prefrontal cortex or the cingulate
      cortex. Previous studies of neglect using a rodent model have indicated that
      disruption of dopaminergic mechanisms may underlie neglect. However, the
      pharmacological results were obtained using a rodent prefrontal model of the
      syndrome (medial agranular cortex), whereas the majority of cases of neglect in
      humans are produced by unilateral destruction of the posterior parietal cortex
      (inferior parietal lobule). The present study examined the effects of
      administration of the dopamine receptor agonist apomorphine on neglect induced by
      unilateral destruction of the posterior parietal cortex (PPC) in rats. The
      results indicated that administration of apomorphine produced a significant dose
      dependent decrease in the severity of neglect. The results support the contention
      that neglect induced by cortical damage may be produced by a disruption of
      dopaminergic mechanisms, and that the PPC may be one component of a cortical
      system for directed attention.

PMID- 8883816
TI  - Effects of an electrolytic lesion of the prelimbic area on anxiety-related and
      cognitive tasks in the rat.
AB  - The aim of this paper was to study the role of the prelimbic area of rats in
      response selection. A bilateral electrolytic lesion was made in the prelimbic
      area. The rats were tested in the Morris water-maze, the conditioned shock-prod
      burying test, the elevated plus-maze, a modified open field test, and the step
      through passive avoidance test. In the water-maze during initial acquisition, the
      latency times of the lesioned rats were not different from those of the controls,
      but they found the platform faster than the sham operated rats after the platform
      was placed in a new position. The lesion did not affect performance in the shock
      prod burying test. In the elevated plus-maze the lesioned rats were more active
      than the sham-operated rats and spent more time on the open arms. In the open
      field there was no difference between lesioned and sham-operated rats with regard
      to distance travelled or the time spent near the object in the center of the open
      field. In the passive avoidance test the lesioned rats had a shorter latency time
      to enter the shock compartment during the retention trial than the sham-operated
      rats did. The results were discussed in relation to those of similar studies. The
      extent and precise localisation of the lesion seems to be crucial for the
      outcome: lesions confined to the prelimbic area may have the opposite effects of
      larger lesions. Furthermore, it may well be that the prelimbic area is only
      involved in processing of stimuli of a specific sensory modality, as made
      probable by the results of different conditioned reinforcement tasks. Finally, it
      was stated that we still lack a hypothesis about the precise role of the
      prelimbic area in response selections.

PMID- 8883817
TI  - Transient impairment of cholinergic function in the rat insular cortex disrupts
      the encoding of taste in conditioned taste aversion.
AB  - The muscarinic antagonist scopolamine blocks conditioned taste aversion (CTA)
      when microinjected bilaterally into the rat insular cortex shortly before the
      exposure of the rat to a novel taste (the conditioned stimulus, CS) in CTA
      training. Scopolamine has no effect when microinjected shortly after the exposure
      to the novel taste or shortly before the application of the malaise-inducing
      agent (unconditioned stimulus, UCS). Scopolamine does not affect sensory, motor
      and retrieval mechanisms required for performing the CTA task, and does not block
      CTA when injected into another cortical area. The effect of scopolamine is
      independent of the taste used as CS. Furthermore, microinjection of scopolamine
      into the insular cortex shortly before the pre-exposure to a new taste in a
      latent inhibition paradigm, impairs the attenuation of CTA by that pre-exposure.
      Other muscarinic antagonists, pirenzepine and AF DX-116, have an effect similar
      to that of scopolamine. Comparison of the dose-dependency curves of the
      muscarinic antagonists suggests a predominant role in CTA for M2 subtype
      receptors. Carbachol, a muscarinic agonist, also impairs the encoding of taste in
      the insular cortex, but the results are confounded by the ability of that ligand
      to induce seizures. Our findings suggest that cholinergic neuromodulation
      participates in processing the CS in the gustatory cortex in CTA, either by
      encoding novelty at the cellular level, or by instructing the neural circuits to
      store the novel taste representation.

PMID- 8883818
TI  - Visuospatial attention in the rat and posterior parietal cortex lesions.
AB  - Covert attention to visuospatial stimuli was assessed in rats using a modified
      version of a task designed for human subjects. Rats were trained to respond
      toward bright target lights presented to the right or left visual space. Dim cue
      lights served to attract their attention prior to the onset of the bright target
      lights. Consistent with previous research using similar paradigms, rats in this
      experiment displayed longer reaction times during trials in which the cue and
      target lights were presented on opposite sides of visual space. Throughout pre-
      and post-operative testing, individual subjects showed lateralized differences in
      the performance of this task as indicated by asymmetries in reaction time, the
      percentage of correct responses, and the number of responses made to each side of
      visual space (response bias). Lesioning the area of cortex thought to be a
      possible homolog of the posterior parietal cortex in primates produced no
      specific effects on performance. It is suggested that this paradigm may tap into
      an evolutionarily conserved attentional process, but that this process may be
      subserved by somewhat different neural structures in different species.

PMID- 8883819
TI  - Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the
      rat: physiological, histological and behavioral correlates.
AB  - This study characterizes physiological, histological and behavioral effects of
      traumatic brain injury (TBI) produced by a controlled pneumatic impactor striking
      the entire right sensorimotor cortex of the anesthetized rat. Damage to both the
      fore- and hindlimb sensorimotor areas resulted in a hemiparetic animal which
      allowed us to use four sensitive behavioral/neurological tests to track the
      recovery sequelae after injury. Initial experiments measured cardiovascular and
      respiratory effects after cortical impact which depressed the dura to varying
      depths. Both 0.5 mm and 1 mm cortical depressions produced a momentary decrease
      (P < 0.05) in mean arterial blood pressure (MABP) while cortical impacts to
      depths of 2 mm or 3 mm produced a momentary increase (P < 0.05) in MABP.
      Normotension was re-established within 30 s after the initial response at all
      injury levels. Respiratory rate was affected only following 3 mm cortical
      depressions. A 1 mm cortical depression appeared ideal in terms of minimal
      cardiorespiratory effects, low mortality and lasting behavioral effects. For
      behavioral and histologic studies, therefore, additional rats were injured by a 1
      mm cortical impact and tested for 8 weeks after TBI using four behavioral tests.
      Injured rats displayed both fore- and hindlimb deficits up to 56 days while
      traversing a narrow beam (P < 0.001) and up to 28 days when crossing a pegged
      beam (P < 0.05). Forelimb deficits evaluated on a wire grid platform were evident
      for 28 days (P < 0.05). Forepaw preference measured in a non-test setting
      indicated a bias to use the unaffected forepaw for 35 days (P < 0.05). A biphasic
      pattern of functional recovery was seen on all tests. A period of rapid
      functional recovery lasting 7 to 10 days was followed by a slower period of
      functional recovery lasting many weeks. Possible meanings of this biphasic
      recovery are discussed as issues of behavioral compensation/adaptation versus
      true neural recovery. Eight weeks after TBI histological analyses indicated that
      axonal degeneration was present in the areas adjacent to the ipsilateral cortical
      injury site. Degenerating fibers also extended across the corpus callosum into
      the homologous area in the contralateral cortex and were seen in the ipsilateral
      striatum, somatosensory and motor thalamic nuclei and substantia nigra.
      Significant axonal degeneration occurred bilaterally around the deep cerebellar
      nuclei. Degenerating fibers extended into the folia and terminated in the
      cerebellar granule cell layer. Thus the entire sensorimotor control system
      appeared to have been affected by a cortical injury.

PMID- 8883820
TI  - Effect of MK 801 on priming of D1-dependent contralateral turning and its
      relationship to c-fos expression in the rat caudate-putamen.
AB  - In rats with a unilateral 6-hydroxydopamine lesion of the ascending dopamine
      neurons, we investigated the relationship between the expression of Fos-like
      immunoreactivity in the caudate-putamen and contralateral turning behavior in
      response to dopamine agonists during the induction and expression of
      sensitization (priming) to D1-dependent turning behavior. Priming was induced by
      apomorphine (0.1 mg/kg s.c.) or by SKF 38393 (10 mg/kg s.c.) 14 days after 6
      hydroxydopamine lesions and was expressed by challenge with SKF 38393 (3 mg/kg
      s.c.). In the induction phase of priming, administration of MK 801 (0.1 mg/kg
      s.c.) potentiated contralateral turning but differentially influenced stimulation
      of Fos expression in the caudate-putamen by apomorphine and by SKF 38393. Thus,
      MK 801 reduced in the expression phase of priming the stimulation of Fos
      expression by apomorphine in the dorsolateral caudate-putamen, but did not affect
      that by SKF 38393. MK 801, while preventing priming of SKF 38393-induced turning
      by apomorphine, failed to affect priming by SKF 38393. MK 801, given with
      apomorphine in the induction phase, reduced the stimulation of Fos expression in
      the dorsolateral caudate-putamen by SKF 38393. No such inhibitory effect of MK
      801 on SKF 38393-stimulated Fos expression was observed in rats primed with SKF
      38393. These results are consistent with the possibility that MK 801 disrupts
      sensitization of D1 transduction by reducing the activation of c-fos by the DA
      agonist during the induction phase of priming.

PMID- 8883821
TI  - Effects of exposure regimen on changes in sensitivity to the effects of cocaine
      on schedule-controlled behavior in rhesus monkeys.
AB  - It has been reported that conditions of drug exposure can influence changes in
      sensitivity to cocaine upon repeated administration. In the present experiment,
      the behavioral effects of prolonged exposure to continuous or intermittent
      infusion of cocaine were compared in rhesus monkeys responding under a multiple
      component fixed-ratio (FR) schedule of food presentation. In order to quantify
      changes in sensitivity to cocaine, cumulative dose-response functions for acute
      cocaine were determined using a multiple schedule comprised of six 10-minute
      components separated by time-out periods of 3 minutes. Initially, cocaine
      decreased responding in a dose-related manner. Continuous infusion of cocaine (4
      mg/kg per day) for a period of 4 weeks resulted in a 2- to 4-fold shift to the
      right in the cocaine dose-response function, i.e., tolerance developed. In
      contrast, when the same daily dose of cocaine was injected intermittently (1.0
      mg/kg per injection) four times/day to different monkeys, there was no change in
      the effects of cocaine on responding. The present results support the notion that
      the dosing regimen is an important determinant of changes in sensitivity to the
      behavioral effects of cocaine. Additionally, since sensitization failed to
      develop upon intermittent administration of cocaine, behavioral baseline may play
      a role in changes in sensitivity to cocaine.

PMID- 8883822
TI  - Behavioral effects of 3 alpha-androstanediol. I: Modulation of sexual receptivity
      and promotion of GABA-stimulated chloride flux.
AB  - Pregnane neurosteroids may initiate sexual receptivity not only via actions at
      intracellular receptors, but by affecting gamma-aminobutyric acid (GABA) receptor
      complexes (GBRs). To investigate whether GBR-mediated actions of an androgenic
      neurosteroid 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol; 3
      alpha-Diol) may influence the expression of sexual behavior, ovariectomized (ovx)
      rats received daily injections of 3 alpha-Diol (0.6, 3.0, 6.0 and 7.5 mg/kg) or
      vehicle (10% (v/v) ethanol in propylene glycol) at 10.00 h, and s.c. injections
      of estradiol-17 beta (E2: 1 microgram/0.2 ml in 10% ethanol) at 13.00 h and 19.00
      h. Progesterone (P: 0.5, 1.0, 2.0 and 4.0 mg/kg) or sesame-oil vehicle was given
      at 12.30 h on the day following two days of 3 alpha-Diol and E2 treatment. In
      Expt. 1, levels of sexual receptivity were measured at 18.00-19.00 h, 56-57 h
      after the first injection of 3 alpha-Diol and 4 h after P or vehicle injection. 3
      alpha-Androstanediol (6.0 mg/kg) attenuated sexual behavior (lordosis quotient,
      lordosis rating) and facilitated aggressive/rejection behaviors following 0.0,
      1.0, 2.0 and 4.0 mg/kg P. The highest dosage of 3 alpha-Diol (7.5 mg/kg)
      facilitated sexual behavior and inhibited aggression behaviors following 0.0,
      1.0, 2.0 and 4.0 mg/kg P. In Expt. 2, GABA-stimulated chloride flux was greater
      in cortical synaptoneurosomes of animals that received hormone treatments
      associated with inhibited receptivity (E2 + P + 3 alpha-Diol 3.0 mg/kg) than
      following treatments that facilitated receptivity (E2 + P and E2 + P + 3 alpha
      Diol 7.5 mg/kg) or unreceptive ovx animals. In Expt. 3, circulating
      concentrations of 3 alpha-Diol resulting from the 0.0, 3.0 and 7.5 mg/kg s.c.
      doses administered to E2- and P-primed animals was measured by radioimmunoassay.
      Circulating levels of 3 alpha-Diol at the completion of behavioral testing were
      comparable to those previously ascertained across the estrous cycle. These data
      indicate that 3 alpha-Diol influences the expression of E2 and P-induced
      receptivity, and suggest that 3 alpha-Diol, like other neurosteroids, may exert
      its effects on sexual behavior by actions at GBRs.

PMID- 8883823
TI  - Behavioral effects of 3 alpha-androstanediol. II: Hypothalamic and preoptic area
      actions via a GABAergic mechanism.
AB  - We investigated whether 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha
      androstanediol; 3 alpha-Diol), a neurosteroid whose effects are primarily
      inhibitory to sexual behavior, may act through interactions with gamma
      aminobutyric acid (GABA) receptor complexes (GBRs) in the medial basal
      hypothalamus (MBH) and the preoptic area (POA). In Experiment (Exp.) 1,
      ovariectomized (ovx) rats were implanted with bilateral guide cannulae aimed
      above the MBH and were later treated with 17 beta-estradiol (E2, 2 injections of
      1 microgram/0.2 ml in 10% ethanol) and either 3 alpha-Diol (3.0 mg/kg, s.c.) or
      vehicle. Progesterone (0.5 mg, s.c.) was given 24 h after the first E2 injection
      and a pre-test for lordosis responsiveness was carried out 4 h later. The GABAA
      agonist, muscimol (50 ng), then was infused into the MBH and rats were tested 10,
      30 and 60 min later. Muscimol infusion facilitated lordosis behavior in vehicle
      treated controls, but 3 alpha-Diol-treated animals failed to show this
      facilitation. To ascertain whether 3 alpha-Diol would also prevent muscimol's
      action in the POA, a site in which muscimol inhibits, rather than facilitates,
      sexual receptivity, ovx animals in Exp.2 were implanted with bilateral guide
      cannulae aimed above the POA and were treated with E2, 3 alpha-Diol, and P and
      infused and tested as in Exp. 1. Muscimol and 3 alpha-Diol each significantly
      inhibited receptivity; when they were combined, the inhibition was more
      pronounced. In Exp. 3, POA infusions of the GABAA antagonist, bicuculline,
      counteracted muscimol's and 3 alpha-Diol's inhibition of sexual behavior. In Exp.
      4, in vitro treatment of POA and MBH membrane fractions with 3 alpha-Diol (30
      microM) enhanced maximal [3H]muscimol binding without altering the affinity of
      the binding sites for the agonist. These data suggest that 3 alpha-Diol inhibits
      E2 and progestin-induced lordosis behavior via actions at the GBR in both the MBH
      and POA.

PMID- 8883824
TI  - Preserved cognitive processes in cerebellar degeneration.
AB  - Aspects of cognitive processing in patients with cerebellar degeneration (CD)
      were studied in order to examine the validity of recent findings that CD patients
      demonstrate deficits in visuospatial cognition and verbal-associative learning.
      Two groups of patients with CD were compared to stratified matched control groups
      on tests examining selective visual attention, visual spatial attention, mental
      rotation of geometric designs, and memory for the temporal order of words they
      were previously exposed to. CD patients performed similarly to their matched
      controls across all tasks. These results indicate that the reported cognitive
      deficits of CD patients are quite selective and need further specification in
      order to more fully describe their relationship to cerebellar dysfunction.

PMID- 8883825
TI  - Comparison of compound and cross-modal training on postoperative visual
      relearning of visual decorticate rats.
AB  - The effects of postoperative bimodal compound conditioning and cross-modal
      transfer of learning on behavior were compared by training rats prior to visual
      decortication to avoid shock with visual intensity cues. On Postop Day 6, rats
      were given avoidance training in one of three cue conditions: auditory intensity
      cues (cross-modal), paired auditory and visual cues (compound conditioning), or
      no cues (no-training control). On Postop Day 7 rats in the no-training control
      and the cross-modal transfer conditions were retrained with the visual
      discrimination while rats in the compound conditioning group were either
      retrained with the visual intensity cue or trained with the auditory intensity
      cue. Postoperative cross-modal transfer training enhanced visual relearning
      whereas bimodal compound conditioning interfered with relearning. However,
      compound conditioning facilitated subsequent auditory discrimination learning.
      These results support the notion of an injury-induced neurological bias that is
      increased after bimodal compound conditioning and reduced after cross-modal
      training. Potential implications for neurological rehabilitation are also
      discussed.

PMID- 8883826
TI  - Bicuculline microinjections into the ventral tegmental area of the rat:
      alteration of self-stimulation thresholds and of cytochrome oxidase activity in
      the brain.
AB  - Abuse of drugs that potentiate GABAergic neurotransmission, namely
      benzodiazepines, is difficult to understand because this potentiation should
      elicit, among other effects, a decrease in activity within the mesolimbic system.
      Abuse of benzodiazepines is difficult to understand since the opposite, namely an
      increase in mesolimbic activity, has been implicated in drug abuse as well as in
      the rewarding effect of direct mesolimbic stimulation. In order to evaluate how
      the activity of the mesolimbic system depends on mesolimbic GABAergic influence,
      a GABAA receptor antagonist, bicuculline methiodide, was unilaterally injected
      into the ventral tegmental area and its effect on self-stimulation thresholds
      derived from stimulations applied to the same area was evaluated. Microinjection
      of 15, 20 and 30 ng increased the stimulation threshold. This decrease in
      stimulation efficiency lasted no more than 15 min after which baseline levels
      were obtained. Such a decrease is paradoxical considering that the manipulation
      should have released the ventral tegmentum from a tonic inhibitory influence. The
      metabolic consequences of repeated injections of 30 ng bicuculline were
      furthermore evaluated by cytochrome oxidase histochemistry. The staining was
      found to be weak around the injection site and dense in the ipsilateral nucleus
      accumbens. Release of a tonic GABAergic inhibition added to some cytotoxic damage
      probably resulted in an increased metabolic activity of this system. The
      presently reported paradoxical response of the ventral tegmentum and mesolimbic
      system to a GABAergic challenge may account for the paradoxical relationship
      between some behavioral properties of the mesolimbic system and GABAergic drugs.

PMID- 8883827
TI  - Suppression of synaptic transmission may allow combination of associative
      feedback and self-organizing feedforward connections in the neocortex.
AB  - Selective suppression of synaptic transmission during learning is proposed as a
      physiological mechanism for combining associative memory function at feedback
      synapses with self-organization of feedforward synapses in neocortical
      structures. A computational model demonstrates how selective suppression of
      feedback transmission allows this combination of synaptic function. During
      learning, sensory stimuli and the desired response are simultaneously presented
      as input to the network. Feedforward connections form self-organized
      representations of input, while suppressed feedback connections learn the
      transpose of the feedforward connectivity. During recall, suppression of
      transmission is removed, input activates the self-organized representation, and
      activity settles into a learned solution to the problem. This computational model
      can be used for learning of problems which are not linearly separable, including
      the negative patterning task (the XOR problem). Experiments in brain slice
      preparations of the rat somatosensory cortex tested whether the combination of
      self-organization and associative memory function could be provided by
      cholinergic suppression selective for feedback versus feedforward synapses. The
      cholinergic agonist carbachol selectively suppressed synaptic potentials elicited
      by stimulation of layer I (which contains a high percentage of feedback
      synapses), while having no effect on synaptic potentials elicited by stimulation
      of layer IV (with a high percentage of afferent and feedforward synapses).

PMID- 8883828
TI  - Skilled forelimb movements in prey catching and in reaching by rats (Rattus
      norvegicus) and opossums (Monodelphis domestica): relations to anatomical
      differences in motor systems.
AB  - Traditional anatomical/behavioral classifications suggest that rats and opossums
      have simple motor systems and are impoverished with respect to their ability to
      make prehensile movements. Nevertheless, the motor system in rats and opossums
      represent extremes in relative size and complexity suggesting that a behavioral
      analysis of the movement competencies of these species will provide insights into
      the significance of such anatomical differences. This paper examines the
      movements that the two species use in catching crickets and in reaching for food
      items. Both species could use a single limb to reach out and grasp prey during
      prey catching and both could use a single limb to take food from a shelf. Both
      species could transport the food to the mouth by using a single paw. The food
      handling behavior of the rats was more complex than that of the opossums,
      however. They used a variety of prey catching movements and extensively
      manipulated the prey to remove the legs and wings before eating only the head and
      body. Additionally the rats made rotatory limb movements of aiming, pronation,
      and supination, when reaching. For both cricket catching and reaching, they used
      their digits more than did the opossums. The suggestion also emerged from the
      results that the movements of the opossums were more fixed and species-typical
      whereas those of the rats were more plastic and individualistic. Thus, the
      skilled movements of both species are more complex than is generally recognized
      and the greater complexity of the rat movements parallels their more complex
      motor system. These results are discussed in relation to anatomical differences
      in the motor system and, specifically, to differences in the terminal fields of
      the pyramidal tract. It is concluded that the motor abilities of nonprimate
      mammals have been vastly underrated.

PMID- 8883829
TI  - Citalopram: differential sleep/wake and EEG power spectrum effects after single
      dose and chronic administration.
AB  - The sleep/wake effects of the selective serotonin re-uptake inhibitor citalopram
      were studied in both a single-dose study with three dose levels (0.5, 2.0 and 5.0
      mg/kg), and a 5-week chronic administration study (15 mg/kg/24 h). Single doses
      of citalopram resulted in a dose-dependent inhibition of rapid eye movement (REM)
      sleep. After chronic citalopram treatment there was a sustained REM sleep
      inhibition. Single doses of citalopram resulted in only minor changes in non-REM
      (NREM) sleep as well as in NREM EEG power spectral density. Chronic
      administration resulted in a major shift from SWS-2 to SWS-1. The observed
      corresponding changes in EEG power density were regional. A 30 to 40 percent
      reduction of power density in the 0.5-15 Hz range in the fronto-parietal EEG
      derivation was seen for the whole 8-h registration period. In the fronto-frontal
      EEG derivation only minor changes were seen. A decreasing trend in NREM sleep
      power density between 0.5 and 7 Hz, usually seen during the course of the light
      period, was not observed in the chronic condition, but was seen in control and
      single-dose condition, suggesting altered diurnal distribution of slow wave
      activity in the chronic condition. The data indicate that acute and chronic
      administration of citalopram shows clear differences in sleep effect, which may
      be caused by alteration of serotonergic transmission, and may be related to the
      antidepressant effect.

PMID- 8883830
TI  - Telencephalic ablation in goldfish impairs performance in a 'spatial constancy'
      problem but not in a cued one.
AB  - This work was aimed to study if goldfish telencephalon is involved differentially
      in spatial and cue learning. With this purpose, animals were assigned to two
      learning conditions, 'spatial constancy' and 'directly cued', and their
      performance was recorded before and after ablation of the telencephalon. During
      the presurgical acquisition period, animals of both groups learned to solve the
      task with accuracy, and reached the goal in transfer tests, even though they were
      released from new starting positions and the response requirements were changed.
      Ablation impaired selectively the solution of the spatial constancy problem, but
      had no significant effects on the cued condition. However, with additional
      training, performance of the ablated animals in the spatial constancy condition
      improved to control levels. The above data suggest that fishes can implement
      multiple spatial learning strategies which have different neural substrata. These
      results are discussed in relation to the possible nature of the representation
      underlying each task.

PMID- 8883831
TI  - Optical control of early visual experience in monkeys.
AB  - Experimental control of the early visual experience of primates has employed a
      variety of surgical manipulations such as suturing the eyelids or cutting the
      extraocular muscles in order to mimic infantile visual disorders of children. For
      several years, we have successfully used optical means for these experimental
      simulations and the methods are described here.

PMID- 8883832
TI  - Loss of stereopsis in monkeys following prismatic binocular dissociation during
      infancy.
AB  - Prismatic binocular dissociation was used during infancy to mimic conditions of
      strabismus in macaque infants. Prisms worn continuously produce a diplopia
      unfavorable for the maintenance and development of the binocular visual system.
      Prism-reared monkeys were tested as young adults and found to be permanently
      stereoblind for dynamic random dot stereograms. Control monkeys did comparably to
      humans on such tests. It is concluded that short periods of diplopia attendant
      with strabismus are sufficient to produce permanent stereoblindness.

PMID- 8883833
TI  - Judgments by monkeys of apparent depth in dynamic random-dot stereograms.
AB  - Young macaques discriminated apparent depths of targets embedded in dynamic
      random dot stereograms; a test of stereopsis. In a 'same/different' paradigm, the
      discrimination took longer if the pair of stimuli appeared to be in same depth
      plane, than when they appeared to be located in a different depth plane. The
      decision time was an inverse function of the disparity difference. Apparent depth
      discrimination performance decreased as a function of disparity, with no
      differences in judgments regarding crossed or uncrossed disparities.

PMID- 8883834
TI  - Excitatory binocular neurons are lost following prismatic binocular dissociation
      in infant monkeys.
AB  - Four infant rhesus monkeys had prismatic dissociation of binocular vision by
      viewing the world through prisms. Those monkeys tested previously for ability to
      utilize horizontal disparity cues in detection of dynamic random dot stereograms,
      were found here to have few excitatory binocular neurons in visual cortex (V1).
      Each eye was well represented in the monocular ability to drive cortical neurons,
      whilst stimulus orientation tuning appeared normal in the monocular neurons, but
      somewhat less sensitive in the remaining binocular neurons. Binocular
      dissociation early in life constitutes conditions unfavorable for the maintenance
      of neural connections delivering binocular excitation to the visual cortex.

PMID- 8883835
TI  - Shrinkage and recovery of cells of the lateral geniculate nuclei with prism
      rearing in macaques.
AB  - Infant macaque monkeys (Macaca mulatta) were subjected to optical dissociation of
      binocular vision by wearing prisms before their eyes for 30 days, beginning about
      30 days of age. Such treatment mimicked strabismus during infancy and resulted in
      a dramatic loss of cortical binocular neurons. A concurrent shrinkage of 21% was
      found in the cells of the lateral geniculate nuclei (LGN) at the end of a
      terminal electrophysiological study at 60 days of age. A group of monkeys
      surviving for 5 years showed recovery of normal cell size, even though they did
      not recover functional binocular neurons in visual cortex.

PMID- 8883836
TI  - Signal transduction and TGF-beta superfamily receptors.
AB  - The TGF-beta superfamily includes a large number of related growth and
      differentiation factors expressed in virtually all phyla. Superfamily members
      bind to specific cell surface receptors that activate signal transduction
      mechanisms to elicit their effects. Candidate receptors fall into two primary
      groups, termed type I and type II receptors. Both types are serine/threonine
      kinases. Upon activation by the appropriate ligand, type I and type II receptors
      physically interact to form hetero-oligomers and subsequently activate
      intracellular signaling cascades, ultimately regulating gene transcription and
      expression. In addition, TGF-beta binds to a third receptor class, type III, a
      membrane-anchored proteoglycan lacking the kinase activity typical of signal
      transducing molecules. Type III receptors appear to regulate ligand availability
      to type I and type II receptors. Although a number of transduction mechanisms may
      be available to TGF-beta superfamily members, evidence gathered through the use
      of specific kinase and G-protein inhibitors and through assays measuring
      activation and levels of signaling intermediates suggests that at least one
      signaling pathway interacts with Ras and Raf proteins via a G-protein
      intermediate. Raf begins the cytoplasmic kinase cascade that leads to gene
      regulation. The myriad responses regulated by TGF-beta superfamily members makes
      the understanding of signal transduction mechanisms utilized by these proteins of
      great interest to a wide range of biological disciplines.

PMID- 8883837
TI  - Hyperthyroidism impairs early repair in normal but not dystrophic mdx mouse
      tibialis anterior muscle. An in vivo study.
AB  - The effect of hyperthyroidism on muscle repair was examined in mdx and control
      mice injected with triiodothyronine (T3) for 4 weeks. On day 24 of treatment, the
      right tibialis anterior (TA) muscle was crush-injured; 3 days later, mice
      received intraperitoneal [3H]thymidine to label newly synthesized DNA. One day
      later, muscles from both limbs were removed to study the severity of dystrophy
      (uncrushed muscle) and the regeneration response (crushed muscle). In uncrushed
      TA muscle, the area of active dystrophy (fiber damage and infiltration as a
      proportion of muscle cross-sectional area) was reduced by half after T3
      treatment. Uncrushed muscle fiber diameter was lower in T3-treated control
      muscles. In crushed muscles, the diameter of new myotubes was larger in mdx mice
      than in controls and was reduced after T3 treatment in control regenerating
      muscle. In the same muscles, developmental myosin heavy chain was present in new
      myotubes and in small numbers of mononuclear cells (possibly differentiating
      myoblasts) near new myotubes and surviving fibers. Myotube density in the
      regenerating muscles was not changed by T3 treatment, although the number of
      myotube nuclei per field was decreased in control and increased in mdx T3-treated
      mice. Results extend previous reports of T3 effects on dystrophy and the strain
      difference in muscle precursor cell (mpc) proliferation. The results also suggest
      the hypothesis that excess T3 affects muscle regeneration either by reducing mpc
      proliferation or by increasing mpc fusion early in regeneration in control and
      mdx muscle.

PMID- 8883838
TI  - Tin ethyl etiopurpurin significantly inhibits vascular smooth muscle cell
      proliferation in vivo.
AB  - Smooth muscle cell proliferation is a major component of restenosis following
      angioplasty. Hematoporphyrin derivative and other photosensitive compounds
      inhibit proliferation by causing cellular necrosis upon light activation
      (photodynamic therapy). Other photosensitive compounds, such as benzoporphyrin
      derivative, have been suggested as having non-cytotoxic antiproliferative effects
      without photodynamic therapy, although other studies using benzoporphyrin
      derivative were negative. Inhibition of smooth muscle cell proliferation was
      examined in an in vivo rabbit model of vascular injury using a novel synthetic
      chlorin derivative, tin ethyl etiopurpurin, and benzoporphyrin derivative without
      photodynamic therapy. Tin ethyl etiopurpurin and benzoporphyrin derivative
      inhibited smooth muscle cell proliferation by 50-90% of control (p < or = 0.05)
      without toxic side effects. These results suggest that tin ethyl etiopurpurin and
      benzoporphyrin derivative without photodynamic therapy may provide a novel and
      potent antiproliferative therapy that might be useful in the treatment of
      restenosis.

PMID- 8883839
TI  - Effects of ultraviolet light in vascular cells in vitro and in intact
      atherosclerotic explants: potential role of apoptosis in vascular biology.
AB  - Complex cell-to-cell interactions are known to participate during vascular injury
      and remodeling, resulting in smooth muscle cell proliferation. Mechanical
      interventions have yielded little benefit in limiting this process and several
      site-specific genetic therapies are not yet clinically available. The aim of this
      study was to delineate the effect of very short wavelength ultraviolet (UVC)
      light therapy on the viability of macrophage and smooth muscle cells. Vascular
      cells were both treated in vitro and in intact explanted atherosclerotic aortic
      segments ex vivo with UVC light. Brief exposure to short wavelength UVC light in
      the absence of photosensitizers elicited a differential temporal and functional
      response among treated cells. However, dramatic reduction in both cellular
      viability and proliferative capacity with eventual cell demise was observed in
      all UVC-treated cells. Flow cytometry and immunohistochemical analyses revealed
      the presence of extensive DNA fragmentation, suggestive of apoptosis as a
      predominant pathway of cell death in these cells exposed to UVC light. We
      hypothesize that selective induction of apoptosis, in contrast to necrosis, with
      UVC light may represent a beneficial approach to interdict the complex biologic
      cascade of messengers that participate in the restenotic response to vascular
      injury.

PMID- 8883840
TI  - Activities of enzymes in platelet activating factor biosynthetic pathways in the
      gerbil model of cerebral ischemia.
AB  - The activities of enzymes in platelet activating factor (PAF) biosynthetic
      pathways were analyzed in hippocampal and cerebral cortical regions of normal and
      ischemic gerbil brain to assess changes in enzyme activities and potential
      modulators that could explain the accentuated production of PAF seen in ischemia.
      Global forebrain ischemia was produced by bilateral carotid artery ligation, and
      the effectiveness of the ligation was shown by free fatty acid release and ATP
      depletion. Specific activities of 1-alkyl-2-acetyl-sn-glycerol (AAG) choline
      phosphotransferase, 1-alkyl-sn-glycero-3-phosphate (AGP) acetyl transferase, and
      1-alkyl-sn-glycero-3-phosphocholine (lyso PAF) acetyl transferase in tissue
      homogenates were in the ratio 4:1:0.1, respectively. Sham-operated and ischemic
      or ischemic-reperfused tissues showed similar activities for individual enzymes,
      indicating that enzyme levels or activation states did not change in ischemic or
      reperfused tissues. However, small metabolites (relevant to ischemia) added to
      the in vitro assays did modify enzyme activities. Physiological concentrations of
      MgATP severely inhibited AGP acetyl transferase activity, and this resulted in
      the ratio of AGP acyl transferase to AGP acetyl transferase activities changing
      from 48:1 in the presence of 2.5 mM MgATP to 6:1 in the absence of MgATP. This
      suggests that falling ATP levels in cerebral ischemia may promote the de novo
      pathway of PAF biosynthesis by releasing inhibition of AGP acetyl transferase.
      Lyso PAF acetyl transferase was much less active than AGP acetyl transferase and
      was also inhibited by MgATP. AAG choline phosphotransferase was not inhibited by
      MgATP but was inhibited by calcium. However the superior specific activity of the
      choline phosphotransferase in comparison with the AGP acetyl transferase
      suggested that the lowered choline phosphotransferase activity in the presence of
      rising intracellular calcium would not seriously compromise the synthesis of PAF
      by the de novo route. Both acetyl transferase enzymes were also inhibited by
      oleoyl CoA.

PMID- 8883841
TI  - Prevention of early glomerulopathy with tolrestat in the streptozotocin-induced
      diabetic rat.
AB  - Hyperglycemia is of central importance in the pathogenesis of the complications
      of diabetes mellitus. Glucose activation of the polyol pathway may lead to renal
      arteriolar smooth muscle and glomerular mesangial cell hypocontractility. In the
      streptozotocin-induced diabetic rat, the effect of the aldose reductase
      inhibitor, tolrestat, in preventing glomerular hyperfiltration, renal
      hypertrophy, extracellular matrix accumulation, and mesangial cell
      hypocontractility was addressed. Streptozotocin-induced diabetic rats were
      followed for 12 weeks and half received tolrestat (25 mg/kg per day). Increased
      glomerular filtration rate was prevented by tolrestat (3.1 +/- 0.3 vs. 1.8 +/-
      0.2 mL/min, diabetes vs. diabetes + tolrestat, p < 0.01), in part by reduction of
      the filtration fraction (0.39 +/- 0.03 vs. 0.29 +/- 0.01, diabetes vs. diabetes +
      tolrestat, p < 0.01). Tolrestat prevented the raised albumin excretion rates
      (3594 +/- 1154 vs. 713 +/- 161 mg/24 h, diabetes vs. diabetes + tolrestat, p <
      0.01). Endothelin-1-induced contraction of isolated glomeruli was normal in
      tolrestat-treated diabetic animals compared with the hypocontractile diabetic
      glomeruli. Tolrestat prevented glomerular hypertrophy (1.86 +/- 0.10 vs. 1.49 +/-
      0.03 microns 2 x 10(5), diabetes vs. diabetes + tolrestat, p < 0.001) and
      attenuated the accumulation of basement-membrane-like material (50.2 +/- 0.4% vs.
      46.4 +/- 0.8%, diabetes vs. diabetes+tolrestat, p < 0.001). Fractional mesangial
      expansion was unchanged in tolrestat-treated diabetic rats compared with
      untreated animals. Tolrestat prevents the functional changes of glomerular
      hyperfiltration, mesangial cell hypocontractility, and increased glomerular
      permeability to albumin. Polyol accumulation may have differential effects on
      glomerular growth and extracellular matrix accumulation in early diabetic
      nephropathy.

PMID- 8883842
TI  - The yeast nucleoporin Nsp1 binds nuclear localization sequences in vitro.
AB  - Facilitated transport of proteins into the nucleus requires nuclear localization
      sequences (NLSs) be present in the protein destined for the nucleus. The specific
      binding of NLSs by components of the nuclear transport apparatus is essential for
      these targeting reactions. We now report that the yeast nucleoporin Nsp1 binds
      specifically nuclear localization sequences in vitro. This nucleoporin recognizes
      several NLSs that are functional for nuclear targeting in vivo, including the NLS
      of SV40 T-antigen and of the yeast transcription factor Ga14. Nsp1 is organized
      into three domains, and we have located NLS binding sites to the N-terminal
      portion and the middle repetitive region of the protein. For the interaction
      between the NLS of SV40 T-antigen and Nsp1, we obtained association constants of
      1.2 x 10(7) M-1 and 5 x 10(7) M-1. An association constant of 5 x 10(7) M-1 was
      determined for NLS binding to the repetitive domain of Nsp1. We analyzed binding
      of Nsp1 and its domains to a mutant version of the NLS derived from SV40 T
      antigen, which poorly functions for nuclear targeting in vivo. The affinity for
      the mutant signal was about two orders of magnitude lower than for the wild-type
      NLS.

PMID- 8883843
TI  - Integrity of the homophilic binding site is required for the preferential
      localization of NCAM in intercellular contacts.
AB  - The neural cell adhesion molecule NCAM is a member of the immunoglobulin (Ig)
      superfamily. NCAM can undergo homophilic binding and heterophilic interactions
      with cell surface components and is often concentrated at sites of intercellular
      contact. To investigate the molecular basis of this biased surface distribution,
      we examined L cell transfectants expressing wild-type or mutant forms of chick
      NCAM-140 by laser scanning confocal microscopy. Mutant NCAMs that lacked Ig-like
      domains 1, 2, 4, or 5 were preferentially localized in contact regions. However,
      the relative concentration of these mutant NCAMs in contact sites was
      substantially reduced compared with wild-type NCAM. In contrast, NCAM
      redistribution to intercellular contacts was abolished in cells expressing mutant
      NCAMs that either lacked Ig-like domain 3 or contained mutations in the
      homophilic binding site in this domain. In heterotypic contacts between PC12
      cells and L cell transfectants, colocalization of rat NCAM and chick NCAM was
      again dependent on the integrity of the homophilic binding site of the NCAM
      expressed on L cells. These results provide evidence that homophilic binding is
      the main mechanism by which NCAM becomes redistributed to intercellular contacts.
      They also implicate a role for other Ig-like domains in the accumulation of NCAM
      at cell-cell contacts.

PMID- 8883844
TI  - A monoclonal antibody against human lipoprotein lipase inhibiting heparin binding
      without affecting catalytic activity.
AB  - A fragment of the human lipoprotein lipase (LPL) cDNA (405 bp, 5' terminal end)
      was cloned in an expression vector to produce a approximately 17 kDa fusion
      peptide and was used as antigen to produce a high titre anti-LPL monoclonal
      antibody (10C3 MAb). This antibody reacts with both native and denatured forms of
      LPL from different tissue and animal sources. Competition studies with heparin
      indicate that 10C3 MAb is specific for an epitope at a heparin binding site. The
      antibody does not inhibit LPL enzyme activity, indicating that the antigenic
      epitope is not situated within or in the proximity of the LPL catalytic region.
      With these characteristics, 10C3 MAb should prove to be a useful immunochemical
      tool in clinical as well as in fundamental investigations on the metabolism of
      triglyceride-rich lipoproteins and in studies on the functional anatomy of LPL.

PMID- 8883845
TI  - Role of oxidative mixed-disulfide formation in elastase-serine proteinase
      inhibitor (serpin) complex.
AB  - To understand the role of thiol and oxidative mixed-disulfide exchange reaction
      in serpins, we analyzed the conformation of native and mixed-disulfide forms of
      alpha 1-proteinase inhibitor (alpha 1-PI), alpha 1-antichymotrypsin (alpha 1
      ACT), alpha 2-antiplasmin (alpha 2-AP), angiotensinogen, and ovalbumin. The
      conformation of native and oxidized mixed-disulfide serpins was measured by
      transverse urea gradient (TUG) gels. The results suggest that the acute phase
      proteins alpha 1-PI and alpha 1-ACT undergo conformational changes following
      oxidative mixed-disulfide formation and that alpha 2-AP and angiotensinogen do
      not. The kinetics of disulfide formation was followed by measuring changes in
      absorbance at 412 nm resulting from Ellman's reaction of disulfide exchange. The
      rate of mixed-disulfide formation in albumin was 10-fold faster than in the
      serpin tested. The rate of disulfide exchange in alpha 1-PI was 2-fold faster
      than that of alpha 1-ACT. However, disulfide formation in alpha 1-PI and alpha 1
      ACT was much slower than for any other serpin, e.g., alpha 2-AP and
      angiotensinogen. We present evidence that alpha 1-PI forms a dimer sensitive to
      thiol reduction, suggesting cysteinyl-mediated dimerization of alpha 1-PI. The
      alpha 1-PI also demonstrated two types of inter-protein disulfide linkages: one
      resulting in homodimer and other involving heterodimer formation. TUG-Western
      immunoblot methodology was developed to identify the conformational changes in
      serpins. We found that the conformational changes in serpins by mixed-disulfide
      formation are due to unfolding and not to decomposition or degradation in TUG
      gels. Using fluorescence measurements with isolated tryptic fragments of
      fluorescence-labelled elastase, we observed that the cysteinyl232 in alpha 1-PI
      interacted with the cysteinyl168 of elastase in the proteinase-inhibitor complex.
      Our data suggests that serpin thiols may play an important role in forming a
      stable serpin-proteinase complex.

PMID- 8883846
TI  - KATP channel-dependent and -independent pathways of insulin secretion in isolated
      islets from fa/fa Zucker rats.
AB  - We hypothesized that altered insulin secretory patterns in obese (fa/fa) Zucker
      rats might be caused by changes in downstream stimulus-secretion coupling events,
      such as ATP-dependent potassium (KATP) channel activity. The functions of KATP
      dependent and -independent pathways of insulin secretion were therefore compared
      in lean and fa/fa Zucker rat isolated islets. KATP channel function was normal in
      fa/fa rat islets, as assessed by responsiveness to direct channel inactivators
      glybenclamide and quinine and by the receptor-mediated response to epinephrine
      and somatostatin. Altered sensitivity to glucose and mannoheptulose were
      explained by upstream alterations in glucose metabolism documented earlier.
      Despite normal inactivation of KATP channels by ATP depletion of fa/fa rat
      islets, glucose-stimulated insulin secretion was not inhibited, leading to
      studies of a putative KATP-independent pathway. When islets were depolarized by
      incubating with 30 mM potassium and 0.25 mM diazoxide to bypass KATP channels,
      glucose elicited a concentration-dependent response in both phenotypes. This
      response required glucose metabolism and Ca2+, as proven by experiments with
      nonmetabolizable glucose analogs and calcium chelation, but was only partially
      inhibited by a glycolytic inhibitor. Intermediates or products of oxidative
      metabolism are likely involved because alpha-ketoisocaproate also elicited a KATP
      independent insulin response. The pattern of responses was similar in lean and
      fa/fa rat islets, indicating that neither of these pathways explains the insulin
      secretion by fa/fa rat islets depleted of ATP. In conclusion, phenotype-related
      differences in KATP channel function were consistent with upstream changes in
      glucose metabolism in fa/fa rat islets. Further studies are required to
      understand the basis of insulin secretion in ATP-depleted islets from fa/fa rats.

PMID- 8883847
TI  - Equilibrium enzymes in metabolic pathways.
AB  - It is commonly believed that certain reactions in a metabolic sequence may be at
      or close to equilibrium because of the large excess of catalytic capacity
      compared to the flux through these enzyme loci. Simple algebraic manipulations
      can show that the equilibrium and steady state conditions are mutually exclusive.
      However, solution of the complete reaction schemes for model "equilibrium"
      reactions shows that they can remain far from equilibrium even though the ratio
      of enzyme flux to steady state flux through the overall pathway is high. These
      calculations show that a reaction's proximity to equilibrium depends on the
      overall flux through the enzyme locus as well as on the kinetic parameters of the
      other enzymes in the pathway. Thus, combinations of kinetic parameters may exist
      that allow certain reactions to approach equilibrium but these conditions are not
      universal.

PMID- 8883848
TI  - Interleukin-2 decreases accumbal dopamine efflux and responding for rewarding
      lateral hypothalamic stimulation.
AB  - Systemic administration of interleukin-2 (IL-2) provoked marked alterations of
      responding for rewarding brain stimulation from the medial forebrain bundle
      (MFB). In particular, when animals were tested for ICSS immediately following IL
      2 treatment only a modest disturbance of responding was evident. However, if
      animals were subsequently exposed to repeated daily ICSS sessions (24-168 h) in
      the drug-free state, rightward shifts in the rate intensity functions and
      significant increases in reward thresholds were apparent. These results were
      dependent upon the presence of IL-2 during the initial ICSS session. If animals
      were tested for ICSS 24 h after IL-2 administration, without an intervening test,
      performance was unaffected. Evaluation of nonreinforced behavior after IL-2
      treatment revealed that ICSS remained under stimulus control and the cytokine did
      not provoke reward-unrelated performance deficits. Dopamine (DA) activity in the
      nucleus accumbens has been implicated in goal-directed responding to positively
      reinforcing stimuli and in the present investigation, using in vivo
      microdialysis, it was observed that IL-2 markedly reduced DA release from this
      region. It was suggested that the protracted consequences of IL-2 on ICSS likely
      do not involve motoric, soporific, attentional or cognitive changes, but may be
      attributable to its specific actions on motivational arousal, possibly engendered
      by the cytokine-induced diminution of accumbal DA efflux.

PMID- 8883849
TI  - Acute and chronic actions of ethanol on CA1 hippocampal responses to serotonin.
AB  - The effects of acute or chronic ethanol on serotonin (5-HT)-induced membrane
      hyperpolarization and inhibition of the slow Ca2(+)-dependent after
      hyperpolarization (sAHP) were recorded in rat CA1 pyramidal neurons in
      hippocampal slices using sharp intracellular electrodes. 5-HT (1-100 microM)
      caused concentration-dependent hyperpolarization of the membrane that was not
      altered by simultaneous 30 mM ethanol treatment, but blunted by 10 microM
      buspirone, a weak 5-HT1A agonist. 5-HT (1-30 microM) also partially inhibited
      (approximately 40%) the sAHP following a burst of five or more action potentials.
      Initially ethanol (30 mM) alone did not alter the sAHP, but over a period of 38
      min, a slow increase in amplitude (approximately 40%) was observed. 5-HT-mediated
      inhibition of the sAHP was significantly greater with ethanol present, regardless
      of the length of exposure. Pyramidal neurons in hippocampal slices prepared from
      ethanol-dependent animals showed no obvious signs of withdrawal related
      hyperexcitability and neither concentration-dependent membrane hyperpolarization
      nor sAHP inhibition caused by 5-HT were significantly changed from responses in
      controls. These results suggest that hyperpolarizing responses to 5-HT in
      hippocampal CA1 pyramidal neurons are functionally resistant to acute or chronic
      ethanol treatment. 5-HT-mediated inhibition of the sAHP is enhanced by ethanol
      acutely, but does not show an adaptive change as a result of ethanol dependence.

PMID- 8883850
TI  - Localization of D1 dopamine receptors on live cultured striatal neurons by
      quantitative fluorescence microscopy.
AB  - Single neurons in culture express a heterogeneity of neurotransmitter receptor
      subtypes. The study of the effects of neurotransmitters on neuronal function is
      complicated by this heterogeneity. It would therefore be useful to be able to
      identify live neurons that express the receptors of interest and then use these
      neurons for functional studies. We have used quantitative fluorescence microscopy
      to identify single live striatal neurons that express D1 dopamine receptors. The
      binding of the fluorescent D1 dopamine receptor antagonist bodipy-SCH 23390 was
      measured in 2-3-week-old primary striatal cultures derived from fetal rats
      (embryonic day 18). Binding of bodipy-SCH 23390 to live neurons was displaced by
      (+)-butaclamol, dopamine or SCH 23390, indicating that it specifically labelled
      D1 dopamine receptors. However, the fraction of bodipy-SCH 23390 binding that was
      specific varied substantially among individual neurons indicating heterogeneity
      of D1 dopamine receptor expression. Interestingly, bodipy-SCH 23390 also
      specifically labelled discrete spots of receptors on the neuronal processes. This
      technique should prove useful in the study of the effects of dopaminergic drugs
      on neuronal function in primary culture.

PMID- 8883851
TI  - Effects of dopaminergic and glutamatergic receptor antagonists on the
      establishment and expression of conditioned locomotion to cocaine in rats.
AB  - A series of experiments were conducted to investigate the role of dopaminergic D1
      and D2 and glutamatergic NMDA and AMPA/kainate receptors on the establishment and
      expression of cocaine-induced conditioned locomotion in rats. In the first
      experiment conditioned locomotion was demonstrated by testing the animals in an
      environment previously associated with 15 mg/kg i.p. cocaine. The D2-receptor
      antagonist (-)-sulpiride (50 and 100 mg/kg i.p.) administered before cocaine
      during the conditioning phase did not modify the establishment of conditioned
      locomotion whereas when administered before testing only at the higher dose it
      partially reduced rats' locomotion in the absence of cocaine (expression). At the
      higher dose (0.1 mg/kg i.p.) the D1-receptor antagonist SCH 23390 attenuated the
      expression of cocaine-induced conditioned locomotion whereas the lower dose (0.03
      mg/kg i.p.) had no effect. Both doses of the NMDA receptor antagonist MK-801
      (0.125 and 0.25 mg/kg i.p.) blocked the development of cocaine-induced
      conditioned locomotion but neither dose, when administered before testing,
      modified locomotion in the absence of cocaine. Both doses of the AMPA/kainate
      receptor antagonist DNQX administered intracerebroventricularly (1 and 3
      micrograms/rat) blocked cocaine-induced conditioned locomotion when given before
      cocaine during conditioning but when given before testing only the higher dose
      attenuated the conditioned activity. The results confirm the importance of the
      interaction between glutamatergic and dopaminergic systems for the conditional
      factors maintaining drug seeking behaviour. The findings may have implications
      for the treatment of cocaine craving and relapse.

PMID- 8883852
TI  - Proliferation of astroglia from the adult human cerebrum is inhibited by ethanol
      in vitro.
AB  - Chronic alcoholism is associated with atrophy of the adult brain, while fetal
      exposure to ethanol can cause microencephaly. Since astroglial pathology is a
      common feature of ethanol exposure in both humans and animal models, the direct
      influence of ethanol on proliferation of human astroglia from the gray and white
      matter of adult temporal lobe was determined and compared. Astroglial cultures
      were exposed to constant concentrations of ethanol at realistic social and
      clinical levels (0.1, 0.2 or 0.5%; w/v) for 1 to 5 days. Proliferation was
      quantified by bromodeoxyuridine labeling and enumeration of replicating cells.
      Ethanol exposure significantly inhibited proliferation of both gray and white
      matter astroglia in a dose and duration dependent manner. Gray matter was
      slightly more sensitive than white matter to inhibition by low to moderate
      concentrations of ethanol; in contrast, white matter was more sensitive to high
      ethanol concentrations. Maximum inhibition was 20% in gray matter and 25% in
      white matter. Human astroglial proliferation was directly inhibited in the
      absence of neurons, microglia, neuronal degeneration or systemic factors that
      have confounded in vivo studies. Restricted astroglial proliferation may underlie
      aspects of the astroglial pathology associated with ethanol exposure.

PMID- 8883853
TI  - Induction of Fos-like immunoreactivity by opioids in guinea-pig brain.
AB  - In the present study the effects of intracerebroventricular (i.c.v.)
      administration of 100 nmol of morphine, the selective mu-receptor agonist DAMGO,
      the delta-receptor agonist DPDPE and the kappa-receptor agonist U50,488H, on the
      induction of Fos-like immunoreactivity (Fos-LI) in the guinea-pig brain were
      investigated using immunohistochemical techniques. Guinea-pigs given i.c.v.
      injection of opioids showed marked increases in the number of Fos-LI nuclei
      within a large number of brain regions, several of which, including hypothalamic
      nuclei, paraventricular thalamic nucleus, the amygdala, periaqueductal gray,
      superior and inferior colliculi, the piriform and entorhinal cortices, have been
      shown to be activated under stressful or aversive conditions. Pretreatment with
      the opioid antagonist, naltrexone, before administration of morphine or U50,488H,
      inhibited Fos-LI induction indicating that the effects of the opioids were
      mediated by opioid receptors. U50,488H administration resulted in higher numbers
      of Fos-LI stained neurons compared to morphine in most regions other than the
      nucleus accumbens and interpeduncular nucleus. Morphine and DAMGO produced
      significantly higher numbers of Fos-LI neurons in the nucleus accumbens shell
      region than U50,488H, which may reflect the more powerful reinforcing/rewarding
      effects of mu-receptor agonists. Thus the present study supports a critical role
      for the nucleus accumbens shell region in the reinforcing/rewarding effects of
      opioids.

PMID- 8883854
TI  - Effect of long-term haloperidol treatment on striatal neuropeptides: relation to
      stereotyped behavior.
AB  - Behavioral and biochemical responses to D1 and D2 dopamine (DA) agonists were
      used to evaluate the participation of striatal peptidergic mechanisms in the
      motor function alterations that attend chronic neuroleptic treatment. Rats, given
      haloperidol (1 mg/kg, i.c.) for 21 consecutive days, were randomly allocated to
      one of the following treatments: the D1 agonist SKF 38393, the D2 agonist
      quinpirole, their combination or saline. Stereotyped behavior and neuropeptide
      levels were evaluated after 5 days treatment and 4 days washout. Haloperidol
      increased most oral behaviors including licking, chewing and biting as well as
      striatal enkephalin and somatostatin levels. Subsequent treatment with SKF 38393
      diminished the haloperidol-induced increase in licking and chewing; quinpirole
      reduced chewing behavior. The administration of both agonists together decreased
      chewing and biting. Neither DA agonist alone, nor their combination, reduced the
      haloperidol-induced increase in enkephalin levels. Both SKF 38393 and quinpirole,
      when given alone, tended to decrease the haloperidol-induced increase in
      somatostatin levels; when both D1 and D2 agonists were administered together,
      somatostatin levels declined significantly. These results suggest that
      somatostatin- but not enkephalin-containing striatal neurons contribute to the
      expression of haloperidol-induced stereotypies.

PMID- 8883855
TI  - The roles of periodontal ligament mechanoreceptors in the reflex control of human
      jaw-closing muscles.
AB  - Controlled mechanical stimuli were applied to an upper central incisor tooth in
      19 human subjects and the resulting reflexes in the ipsilateral masseter muscle
      were examined electromyographically. In most cases the force profile of the
      stimuli consisted of a ramp leading to a sustained plateau at an intensity of 1
      N. In addition 1 N tap stimuli were employed in some subjects. The 1 N ramp
      stimuli with a rise time of < or = 20 ms consistently evoked a single, short
      latency (approximately 12 ms), inhibitory reflex which was often followed by an
      excitatory wave. The ramp stimuli with shorter rise times produced larger
      responses than those produced by ramp stimuli with longer rise times. By contrast
      the tap stimuli elicited a sequence of responses consisting of inhibitory
      excitatory-inhibitory-excitatory components. The first inhibitory and excitatory
      responses evoked by tap stimuli had latencies similar to those of the responses
      evoked by the ramp stimuli. The latencies of the inhibitory responses evoked by 1
      N ramps with rise times ranging between 2.5 and 20 ms did not vary significantly
      with the rise time. Consistent with this observation it was found that the median
      threshold force for evoking the short-latency inhibitory reflex was only 0.25 N.
      This was significantly less than the threshold for the excitatory response
      (median: 0.75 N). The responses to ramp-plateau forces were not dependent on the
      level of preloading of the tooth (at least within the range tested: < 0.25 to 1
      N). These findings provide evidence that mechanoreceptors in the periodontal
      ligament contribute to the control of human jaw-closing muscles, notably to short
      latency reflex responses. It may be concluded that the additional reflex
      responses produced by tapping stimuli result from the activation of receptors
      elsewhere due to vibration.

PMID- 8883856
TI  - The glycine/NMDA receptor antagonist HA-966 impairs visual recognition memory in
      rhesus monkeys.
AB  - Recent studies have shown that strychnine-insensitive glycine binding sites
      positively modulate the N-methyl-D-asparate (NMDA) subclass of glutamate
      receptors, which are important in neural pathways involved in cognitive function.
      We examined the effect of (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), a
      highly specific antagonist of this glycine modulatory site on the NMDA receptor,
      on visual recognition memory in four rhesus monkeys performing a computer
      automated version of delayed nonmatching-to-sample (DNMS) with a list length of
      20 trial-unique graphic symbols. In addition, the effect of HA-966 was compared
      with that of (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine
      (dizocilpine; MK-801), a noncompetitive NMDA channel blocker. Administration of
      HA-966 (0.1-10 mg/kg, i.m.) 30 min before testing impaired DNMS performance dose
      dependently, starting at doses of 3.2 mg/kg; the memory deficity following the
      highest dose (10 mg/kg) was associated with prolonged response latencies. Similar
      impairments in recognition memory were observed following treatment with MK-801,
      though at much lower doses (3.2-32 micrograms/kg) than those at which HA-966 was
      effective. Administration of low doses of HA-966 (1 mg/kg) and MK-801 (10
      micrograms/kg), each of which had no significant effect on performance when given
      alone, also failed to impair performance when given concurrently. Combined
      administration of both drugs, each at amnesia-producing doses (3.2 mg/kg of HA
      966 plus 32 micrograms/kg of MK-801), markedly impaired performance in an
      additive, not a synergistic, manner. From these results, we propose that the
      recognition memory impairment observed in our monkeys following HA-966
      administration is via an action on the glycine modulatory site of the NMDA
      receptor complex.

PMID- 8883857
TI  - Regulation of glucocorticoid and mineralocorticoid receptor mRNAs in the
      hippocampus of the maternally deprived infant rat.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis in the developing rat has a limited
      response to acute challenges between days 3 and 14 of life. Several hypotheses
      have been proposed to explain this quiescent state. Immaturity of brain,
      pituitary and adrenal elements or excessive feedback inhibition are common
      explanations. Recently, a series of studies by Levine and co-workers has shown
      that prolonged maternal deprivation (24 h) results in increased basal and stress
      induced corticosterone (CS) levels. An increased adrenal response to ACTH along
      with an enhanced and sustained ACTH response have been implicated in this
      phenomenon. A brain structure that appears to be important for normal HPA
      function is the hippocampus, a structure rich in corticosteroid receptors, which
      has been hypothesized to play a role in the basal tone of the HPA and in the
      magnitude and duration of stress responses. Thus, to study further the possible
      mechanisms leading to an enhanced and sustained ACTH response that is seen in
      maternally deprived pups, we used in situ hybridization to investigate
      hippocampal mineralocorticoid (MR) and glucocorticoid receptor (GR) gene
      expression in 12 groups of animals: six groups involved 24 h maternally deprived
      (DEP) and non-deprived (NDEP) rat pups at three ages (6-, 9-, and 12-days-old);
      the other six groups included pups similarly treated, but challenged with an
      exposure to a mild stressor (saline injection) and sacrificed 1 h thereafter. We
      found: (1) an age effect for almost every hippocampal subfield for both MR and GR
      mRNAs: MR increases with age, while GR decreases: (2) down-regulation of MR mRNA
      in CA1 region in the DEP animals; and (3) down-regulation of GR mRNA, also in
      CA1, in the saline-injected DEP and NDEP animals. Our results indicate that
      corticoid receptors in the developing CA1 hippocampal region appear to be
      sensitive to circulating CS. They also suggest that the relative ratio of GR and
      MR in the CA1 region may contribute to the enhanced and sustained CS response
      seen after a mild stressor in deprived animals.

PMID- 8883858
TI  - Stimulus-dependent oscillations in the cat visual cortex: differences between bar
      and grating stimuli.
AB  - We have investigated the dependence of cortical oscillations on the type of
      visual stimulus. Single unit recordings were performed in areas 17 and 18 of the
      cat visual cortex. Among 217 cortical neurons oscillations in the frequency range
      of 22-102 Hz were found in 29 cells (13%). The proportion of oscillating cells
      was higher (16%) if both bar and grating stimuli were used to stimulate cortical
      neurons. It was found that gratings are more effective than bars in triggering
      oscillatory patterns in cortical cells. Among 21 oscillating cells which were
      stimulated with both bar and grating stimuli, oscillations evoked with gratings
      were found in 17 neurons (81%) while oscillations evoked with bar stimuli were
      triggered in 7 cells (33%). The distributions of oscillation frequencies were
      statistically different for oscillations evoked with bars and gratings.
      Frequencies of oscillations evoked with bars were in the lower and higher range
      than frequencies of oscillations evoked with gratings. In 3 cells (14%), rhythmic
      patterns could be evoked with both bar and grating stimuli. However, the
      oscillations were of different frequencies. No significant correlation was found
      between the strength of oscillations and firing rate of cortical neurons. Both
      simple and complex cells manifested the same dependence on stimulus type.
      However, complex cells mostly exhibited oscillations in the lower frequency range
      while simple cells did so when neurons were stimulated with bars. The results
      suggest that various classes of visual stimuli can be coded by a temporal pattern
      of cortical responses.

PMID- 8883859
TI  - Ultrastructural evidence for a separate, small synaptic vesicle (SSV) pathway in
      ligated bovine splenic nerves, incubated in vitro.
AB  - In sympathetic nerves the tubules of the axonal reticulum make up the immature
      elements of the neurosecretory apparatus. The formation of the mature large dense
      granules occurs via a less dense tubular intermediate, representing the maturing
      part. At a terminal small synaptophysin-positive vesicles are found intermingled
      with the dense granules. The biogenesis of these clear, small synaptic vesicles
      and their relationship with dense granules remains to be determined. In search
      for the small synaptic vesicles we undertook a careful ultrastructural
      examination of the axons proximal to a ligation in bovine splenic nerve incubated
      in vitro for 3 h. The distended axons were crowded with tubules, granulo-tubular
      elements and dense granules. Occasionally homogeneous clusters of small, uniform
      vesicles were detected. They were shown to be positive for synaptophysin and were
      negative for dopamine-beta-hydroxylase, a marker for the granular pathway. The
      clusters of small vesicles could be found in close spatial relationship with the
      maturing and mature elements of granular secretion. Our findings argue for the
      presence of two separate neurosecretory pathways in sympathetic nerves and favour
      the idea that both small synaptic vesicles and dense granules are a
      differentiation product of the axonal reticulum. This configuration can explain
      the biogenesis of small synaptic vesicles and dense granules both in the cell
      body and at the nerve terminal.

PMID- 8883860
TI  - The amiloride-sensitive Na+/H+ exchange antiporter and control of intracellular
      pH in hippocampal brain slices.
AB  - The intracellular pH, 7.54 +/- 0.03 (mean +/- S.D., n = 15), determined with the
      Neutral red method, of the hippocampal brain slice preparation under baseline
      incubation conditions is considerably more alkaline than the bath buffer pH.
      Neutralization by amiloride suggests that the alkalinity was due to Na+/H+
      exchange antiporter activation. To characterize the brain Na+/H+ exchange
      antiporter we compared the inhibitory effects of MIA, amiloride and other 5-N
      substituted analogues on proton extrusion after acid loading by transient
      exposure to ammonium chloride in the isolated hippocampal brain slice
      preparation. The potencies of amiloride compounds on the initial recovery rate of
      intracellular pH after acid-loading were DMA > MIA > HMA = MHA > or = IPA-HCI >
      IPA > MNPA = Amil > Benzamil. The greater potency of the 5-N substituted analogs
      of amiloride over amiloride and benzamil strongly suggest that Na+/H+ exchange
      antiporter is the mechanism responsible for alkalinization in the isolated
      hippocampal brain slice in vitro.

PMID- 8883861
TI  - Calmodulin inhibitors induce spinal analgesia in rats.
AB  - Calcium is an important intracellular messenger that interacts with Ca(2+)
      binding proteins, such as calmodulin (CaM), to activate several intracellular
      enzymes. The involvement of Ca2+ in the transmission of nociceptive signals has
      been demonstrated at the spina level. Specifically, spinal sensitization induced
      by persistent nociceptive stimulation seems to be related to an increase of
      cytosolic calcium and the subsequent activation of several enzymes, some of which
      are Ca2+/CaM dependent. In order to elucidate the possible implication of
      calmodulin in these pain processes, we have studied the effect of two calmodulin
      inhibitors (W-7 and calmidazolium) or the formalin and tail-flick tests in rats
      after their intrathecal administration. Antinociceptive effects were observed in
      both tests by injecting 0.12-1 mumol/rat of calmidazolium and 0.25-2 mumol/rat of
      W-7. Calmidazolium was more potent than W-7 in inhibiting both phases of the
      formalin test, whereas lower doses of W-7 in comparison to calmidazolium affected
      the tail-flick latencies. In addition, both drugs induced, at high doses, a
      muscular flaccidity of the hindlimbs that impaired normal walking in the rats.
      This effect caused; significant reduction of the rotarod performance when 1
      mumol/rat of calmidazolium or 2 mumol/rat of W-7 were injected. Overall, our
      results show that calmodulin inhibitors are capable of producing spinal analgesia
      on phasic and tonic noxious stimuli in rats, thus rendering them a promising
      potential as analgesics.

PMID- 8883862
TI  - Salutary and deleterious effects of acidity on an indirect measure of metabolic
      rate and ATP concentrations in CNS cultures.
AB  - Acidosis has traditionally been considered to mediate certain types of hypoxic
      ischemic injury to the brain. However, the recent demonstration that moderate
      acidosis will reduce NMDA-mediated currents suggested that acidity could actually
      protect against types of ischemia and excitotoxicity, and in vitro studies now
      support this idea. Prompted by this, we have utilized the silicon
      microphysiometer, a recently-developed instrument that allows for indirect real
      time measurement of metabolic rate by detecting proton efflux from small numbers
      of cultured cells, to determine whether acidity has protective effects upon
      cellular metabolism. Reducing extracellular pH from 7.4 to as low as 6.0 caused
      prompt, step-wise, and reversible inhibition of proton efflux rate in cortical
      and hippocampal cultures both normally and restricted to either glycolysis or
      oxidative metabolism. Approximately half of the inhibition was due to acidotic
      effects of NMDA-mediated currents, as demonstrated with NMDA receptor
      antagonists. Such an inhibition of this indirect metabolic measure could be
      associated with constant or increased ATP concentrations and represent a
      beneficial decrease in energy demands upon a neuron. Alternatively, an inhibition
      of proton efflux rate could be associated with ATP depletion and reflect impaired
      energy production. We observed a complex interplay between these opposing
      patterns. Reducing pH to 6.7 for 20 min caused significantly increased ATP
      concentrations, and prevented excitotoxin-induced ATP depletion. These effects of
      acidosis involved both NMDA-dependent and- independent actions. More severe (less
      than pH 6.7) acidosis did not cause ATP concentrations to rise, and if sustained
      for more than an hour caused a significant decline in ATP concentrations. Thus,
      despite the recent emphasis on the surprising neuroprotective potential of
      acidosis, a drop in pH is still likely to have complex and mixed consequences for
      brain tissue.

PMID- 8883863
TI  - Changes in [3H]AMPA and [3H]kainate binding in rat caudate-putamen and nucleus
      accumbens after 6-hydroxydopamine lesions of the medial forebrain bundle: an
      autoradiographic study.
AB  - The binding parameters of [3H] alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA) and [3H]kainate binding were examined in caudate
      putamen and nucleus accumbens of rat striatum after unilateral lesions of the
      right medial forebrain bundle (MFB) using in vitro receptor autoradiography.
      Lesioning of the dopaminergic fibres in the MFB with 6-hydroxydopamine (6-OHDA)
      resulted, after one or four weeks, in a significant decrease in the levels of
      [3H]GBR 12935 (1-[2-diphenylmethoxy)-ethyl]-4-(3-phenylpropyl) piperazine) in
      ipsilateral caudate-putamen and nucleus accumbens (62 and 43%, respectively). A
      comparison of the dissociation constants (Kd) of [3H]AMPA and [3H]kainate binding
      in caudate-putamen and nucleus accumbens between control and MFB-lesioned side
      did not indicate any significant change. However, the maximum number of [3H]AMPA
      and [3H]kainate binding sites (Bmax) were significantly decreased in caudate
      putamen and nucleus accumbens of the MFB-lesioned side of the brain. This
      decrease was between 17 and 26%. Our results suggested that at least one-fourth
      to one-fifth of AMPA and kainate receptors in rat caudate-putamen and nucleus
      accumbens are localized on the presynaptic endings of dopamine fibres that follow
      the MFB. A role of non-NMDA glutamate receptors in the presynaptic regulation of
      dopamine release in rat striatum is therefore supported.

PMID- 8883864
TI  - Ultrastructural localization of mu-opioid receptors in the superficial layers of
      the rat cervical spinal cord: extrasynaptic localization and proximity to Leu5
      enkephalin.
AB  - Many of the analgesic effects of opiate drugs and of endogenous opioid ligands,
      such as Leu5-enkephalin (LE) are thought to be mediated in part by mu-opioid
      receptors (MOR) in the dorsal horn of the spinal cord. To establish the cellular
      sites for the spinally mediated analgesic effects of MOR activation and the
      potential anatomical substrates for interactions with LE, we examined the
      ultrastructural localization of MOR and LE immunoreactivities in the adult rat
      cervical spinal cord (C3-C5). Anti-MOR sera recognizing the carboxyl terminal
      domain of MOR was localized using immunoperoxidase and immunogold-silver methods.
      mu-opioid receptor-like immunoreactivity (MOR-LI) was observed mainly in the
      superficial layers of the dorsal horn. Electron microscopy of this region
      revealed that small unmyelinated axons and axon terminals constituted 48%
      (91/189) and 15% (28/189), respectively, while dendrites comprised 36% (68/189)
      of the total population of neuronal profiles containing the MOR. MOR-LI was
      localized mainly along extrasynaptic portions of the plasma membrane in both
      axons and dendrites. In sections dually labeled for MOR and LE, 21% (14/68) of
      the dendrites containing MOR-LI closely apposed or received synaptic contact from
      axon terminals exhibiting LE reaction product. The results provide the first
      ultrastructural evidence that within the dorsal horn of the spinal cord, LE, as
      well as exogenous opiates may alter both axonal release of neurotransmitters and
      postsynaptic responsiveness of target neurons to afferent input through
      activation of extrasynaptic MOR.

PMID- 8883865
TI  - Physiological adjustments in a reflex pathway following partial loss of target
      neurons.
AB  - This investigation was undertaken to study plasticity in a reflex pathway
      following partial elimination of target neurons. Adult cats were subjected to
      unilateral avulsion of the L7 spinal ventral root, which induces retrograde cell
      death among the motoneurons of the L7 segment. At 1, 3, 6 and 12 weeks after the
      lesion, the monosynaptic reflexes were recorded in the L6 and S1 ventral roots
      during stimulation of the L6, L7 and S1 dorsal roots. Since the group Ia muscle
      spindle afferents passing through these dorsal roots were deprived of their
      target motoneurons in the L7 segment, compensatory reflex changes were searched
      for in the remaining monosynaptic contacts with the intact target motoneurons of
      the L6 and S1 segments. The results indicate that a partial loss of target
      motoneurons triggers changes leading to increased monosynaptic reflexes of the
      remaining intact target motoneurons. On average, the reflexes had more than
      doubled their size at 12 weeks postoperatively. Possible mechanisms for this
      reflex potentiation are discussed.

PMID- 8883866
TI  - Endothelial cell-based cytokine gene delivery inhibits 9L glioma growth in vivo.
AB  - Malignant brain neoplasms present great therapeutic challenges due to their
      extremely aggressive behavior and relative isolation by the blood-brain and blood
      tumor barriers. Endothelial cells may be versatile platforms for delivering genes
      to solid tumors by virtue of their location at blood-tissue interfaces and their
      proliferation in response to endothelial mitogens produced by tumors.
      Immortalized rat brain endothelial cells that express the E. coli lacZ reporter
      gene and the gene for murine interleukin-2 (RBEZ-IL2) were co-inoculated with 9L
      glioma cells to Fisher rats to examine the effects of endothelial cell-based
      cytokine delivery on glioma growth in vivo. 9L glioma growth was not affected by
      the implantation of control RBEZ cells. The growth of subcutaneous and
      intracranial 9L gliomas was significantly inhibited by RBEZ-IL2 cells (P < 0.005
      and P < 0.01, respectively) when compared to control transfected RBEZ cells. Rats
      receiving intracranial 9L glioma cells with RBEZ-IL2 cells showed increased
      survival (P < 0.001). Histologic and immunohistologic analysis showed enhanced
      activation of microglia/macrophages and CD8-positive T lymphocytes and/or natural
      killer cells within brain at sites of 9L inoculation with RBEZ-IL2 cells. This
      report establishes that immortalized endothelial cells can be used for cytokine
      gene delivery and to activate anti-tumor host responses to experimental gliomas
      within the central nervous system.

PMID- 8883867
TI  - Inhibition of morphine tolerance by NMDA receptor antagonists in the formalin
      test.
AB  - 5-Nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328) was
      characterized in vitro for antagonism of excitatory amino acid receptors, and
      subsequently tested in vivo and compared with MK-801 for phencyclidine (PCP)-like
      motor stimulation, antinociception, and effects on morphine tolerance in mice.
      Assayed on rat cerebral cortical glutamate receptors expressed in Xenopus oocytes
      ACEA-1328 showed potent (Kb approximately 40 nM) antagonism at NMDA
      receptor/glycine sites and moderate (Kb approximately 3 microM) antagonism at non
      NMDA receptors. In both cases inhibition was predominantly competitive. ACEA-1328
      was weak, or inactive, at NMDA receptor glutamate recognition sites, metabotropic
      receptors and opioid binding sites. In the formalin and rotarod tests ACEA-1328
      and MK-801 produced both antinociception and disturbances of motor coordination.
      MK-801 caused a PCP-like motor stimulatory effect, whereas ACEA-1328 was devoid
      of such an effect. In tolerance studies, ACEA-1328 and MK-801 each blocked
      morphine tolerance in the formalin test, the effect of ACEA-1328 was dose
      dependent. Our data contribute to a growing body of evidence which suggests that
      activation of NMDA receptors is critical for the development of opioid tolerance,
      and that antagonism at NMDA receptor/glycine sites may have potential as a means
      of diminishing tolerance with no PCP-like motor stimulatory side effects.

PMID- 8883868
TI  - Distribution of Lys-gamma 2-melanocyte-stimulating hormone- (Lys-gamma 2-MSH)
      like immunoreactivity in neuronal elements in the brain and peripheral tissues of
      the rat.
AB  - Using an antiserum raised against Lys- gamma 2-melanocyte-stimulating hormone
      (Lys- gamma 2-MSH), with a high specificity for this peptide and its des-Lys
      derivative, gamma 2-MSH, we found Lys- gamma 2-MSH-like immunoreactivity to have
      a widespread distribution in the rat brain. In colchicine-treated rats, groups of
      immunopositive cell bodies were found in the intermediate and anterior lobes of
      the pituitary gland, in the hypothalamic arcuate nucleus and in the commissural
      part of the nucleus of the solitary tract (NTS). Immunopositive fibers were found
      to originate from the latter two cell body regions. The distribution of these
      fibers was similar to that of the pro-opiomelanocortin containing cell bodies and
      projections as it has been described previously. Immunopositive terminals were
      found in brain region containing neurons which have been shown to express mRNA
      for melanocortin receptors, though the distribution of Lys-gamma 2-MSH-like
      immunoreactivity is considerably more widespread than that of mRNA for the 'gamma
      MSH receptor' (the melanocortin MC3 receptor), which has been reported to be
      mainly expressed in the hypothalamus. In the periphery Lys-gamma 2-MSH
      immunoreactivity was localized in the adrenal medulla and in neuronal fibers and
      varicosities in the heart. The vascular system, the bronchi and kidney were
      immunonegative. The occurrence of Lys-gamma 2-MSH immunoreactivity in many of the
      brain regions which are involved in cardiovascular regulation offers leads for
      further studies on the putative role of gamma-MSHs in cardiovascular control. The
      occurrence in the rat heart of Lys-gamma 2-MSH-containing fibers suggests a role
      of the gamma-MSHs in cardiac function.

PMID- 8883869
TI  - Relationships between convulsive seizures and serum and brain concentrations of
      phenobarbital and zonisamide in mutant inbred strain EL mouse.
AB  - We evaluated the anticonvulsive effects of phenobarbital (PB) and zonisamide
      (ZNS) in the EL mouse, a strain that is highly susceptible to seizures. The
      concentration of each agent was analyzed in the serum and brain. PB suppressed
      the seizures dose-dependently, whereas even the higher dose of ZNS was
      ineffective in achieving a complete suppression. Serum and brain concentrations
      of these two drugs increased in proportion to the higher dose injected
      intraperitoneally. Brain concentration of PB was lower than the serum
      concentration, while the brain concentration of ZNS exceeded that in serum.
      Although serum concentration of ZNS was essential unchanged after the combined
      administration of PB and ZNS, the concentration of ZNS in brain tended to rise in
      proportion to the highly dose of PB. Combined administration was more effective
      than other treatment alone. Results indicated that brain concentration of ZNS
      especially after concomitant PB administration, were higher than that would be
      expected from the concentration of ZNS in serum.

PMID- 8883870
TI  - The type 3 serotonin receptor is expressed in a subpopulation of GABAergic
      neurons in the rat neocortex and hippocampus.
AB  - We used in situ hybridization and immunocytochemistry to investigate the presence
      of GABA in neurons that express the type 3 serotonin receptor (5-HT3R).
      Quantitative analysis indicated that more than 90% of 5-HT3R expressing cells are
      GABAergic in the neocortex and hippocampus. The co-existence of 5-HT3R and GABA
      in cortical and hippocampal neurons indicates that serotonin, via 5-HT3R, can
      affect GABA release and suggests the participation of 5-HT3R in the inhibitory
      regulation of forebrain neurons.

PMID- 8883872
TI  - The neuroprotective efficacy of MK-801 in focal cerebral ischemia varies with rat
      strain and vendor.
AB  - The present study was designed to evaluate whether the neuroprotective efficacy
      of MK-801 in focal cerebral ischemia was dependent on strain and/or vendor
      differences. MK-801 (0.12 mg/kg i.v. bolus followed by 0.108 mg/kg/h infusion or
      0.60 mg/kg i.v. bolus followed by 0.540 mg/kg/h infusion) or saline was
      administered just after intraluminal middle cerebral artery occlusion.
      Administration of 0.540 mg/kg/h MK-801 provided strain/line-dependent
      neuroprotection in the following rank order: Simonsen Laboratories Sprague-Dawley
      rats > Simonsen Laboratories Wistar rats > Taconic Laboratories Sprague-Dawley
      rats. After 0.108 mg/kg/h MK-801 treatment, Simonsen Laboratories Wistar rats
      were the only strain/line that were significantly neuroprotected. These results
      indicate that the neuroprotective effect of an experimental drug may be
      influenced by rat strain and vendor differences.

PMID- 8883871
TI  - The alpha 2 adrenoreceptor agonist clonidine suppresses seizures, whereas the
      alpha 2 adrenoreceptor antagonist idazoxan promotes seizures: pontine
      microinfusion studies of amygdala-kindled kittens.
AB  - This is the first report showing that microinfusion of alpha 2 adrenoreceptor
      agonists and antagonists into the vicinity of the locus ceruleus (LC) have
      contrasting effects on evoked amygdala-kindled seizure susceptibility.
      Microinfusion (1 microliter) of the alpha 2 agonist clonidine (CLON) and of the
      alpha 2 antagonist idazoxan (IDA) were made over 1 min through cannulae in the LC
      ipsilateral to the kindled amygdala in 6 kittens. Order of administered drugs
      (CLON vs. IDA) and dosages (n = 3 each) were partly counterbalanced. Focal and
      convulsive seizure thresholds were evaluated 10-12 min post-infusion and compared
      to thresholds obtained during two, interspersed control conditions (vehicle
      control = 1 microliter microinfusion of sterile saline; sham control = needle
      insertion only). CLON significantly elevated focal and generalized seizure
      thresholds, whereas IDA significantly reduced seizure thresholds when compared to
      controls. Magnitude of effects was dose-dependent. These findings confirm that
      norepinephrine (NE) is a potent antiepileptic agent. Results also suggest that
      pontine microinfusions could eventually provide an alternative treatment option
      for medically refractory limbic epilepsy.

PMID- 8883873
TI  - Glutamate and vasopressin interact to control scent marking in Syrian hamsters
      (Mesocricetus auratus).
AB  - In Syrian hamsters, vasopressin (AVP) in the medial preoptic-anterior
      hypothalamus (MPOA-AH) controls a form of scent marking called flank marking.
      Another neurochemical signal that may interact with AVP to control flank marking
      is glutamate. We tested the hypothesis that glutamate interacts with AVP in the
      MPOA-AH to regulate flank marking. On day 1, AVP was microinjected into the MPOA
      AH. On day 2, AVP was microinjected as a cocktail combining either AP-5, a NMDA
      antagonist, or GAMS, a non-NMDA antagonist or propranolol, a beta norepinephrine
      antagonist. On day 3, AVP alone was microinjected. Hamsters engaged in high
      levels of marking in response to AVP alone or to a combination of AVP and
      propranolol. In contrast, the frequency of marking was significantly reduced in
      response to a combination of either AVP and AP-5 or AVP and GAMS. These data
      support the hypothesis that stimulation of flank marking by AVP within the MPOA
      AH requires the activity of glutamate.

PMID- 8883874
TI  - Platelet/endothelial cell adhesion molecule-1 (PECAM-1) expression by human brain
      microvessel endothelial cells in primary culture.
AB  - PECAM-1 expression was investigated in primary cultures of human brain
      microvessel endothelial cells (HBMEC). HBMEC constitutively express PECAM-1 along
      their apical cell surface, advancing processes and on the basal surface at points
      of contact with the extracellular matrix. Surface expression is not altered by
      cytokine or lipopolysaccharide treatment. This distribution may mediate cell-cell
      contract and migration during angiogenesis and HBMEC-leukocyte interactions in
      CNS inflammation.

PMID- 8883875
TI  - Constant light induces persistent Fos expression in rat intergeniculate leaflet.
AB  - Fos protein expression in retinorecipient suprachiasmatic nucleus (SCN) neurons
      is a marker of photic entrainment of circadian rhythms. Light-induced Fos in
      neurons of the intergeniculate leaflet (IGL) is not well-characterized. We
      compared Fos immunoreactivity (Fos-IR) in SCN and IGL neurons of rats housed
      under various lighting conditions and sacrificed at different phases of the
      circadian period. IGL neurons of rats that received 1 h-3 weeks of light exposure
      prior to sacrifice displayed Fos-IR, whereas the IGL of animals exposed only to
      darkness displayed little if any staining. In contrast with light-induced Fos in
      SCN neurons, Fos-IR was observed in the IGL regardless of circadian time. This
      work supports the idea that the IGL is involved in transmission of photic
      information to the SCN in rats.

PMID- 8883876
TI  - Effects of ibogaine and noribogaine on phosphoinositide hydrolysis.
AB  - The effects of the antiaddictive compound, ibogaine, and its primary metabolite,
      noribogaine (12-hydroxyibogamine), on phosphoinositide hydrolysis were
      investigated. Although ibogaine did not alter phosphoinositide turnover in either
      striatal or hippocampal slices, noribogaine elicited a concentration-dependent
      increase in the generation of [3H]inositol phosphates. This stimulation was not
      altered by inclusion of tetrodotoxin, cadmium or omega-conotoxin indicating that
      the increased production of [3H]inositol phosphates was not secondary to a
      release of one or more neurotransmitters. The present study indicates a
      stimulation of phosphoinositide hydrolysis by noribogaine may be involved in the
      behavioral effects of ibogaine.

PMID- 8883877
TI  - Presynaptic muscarinic cholinergic receptors in the dorsal hippocampus regulate
      behavioral inhibition of preweanling rats.
AB  - The aim of this research was to determine whether early maturation of the dorsal
      hippocampal cholinergic system mediates behavior exhibited by preweanling rats in
      the presence or absence of an unfamiliar adult male rat, a threatening stimulus.
      The behavioral responses that were examined included behavioral inhibition or
      freezing which emerges at 2 weeks of age and ultrasonic vocalizations. Prior to
      behavioral testing, oxotremorine, an M2 muscarinic receptor agonist that reduces
      cholinergic release from presynaptic terminals, was infused into the dorsal
      hippocampal dentate gyrus. Results demonstrated that 14-day-old rats with
      bilateral hippocampal infusions of a 1 microgram dose of oxotremorine exhibited
      significant deficits in freezing when exposed to the adult male rat. Importantly,
      oxotremorine had no significant effects on ultrasound emission and ambulatory
      activity when rat pups were tested in social isolation. Thus, effects of
      oxotremorine in the hippocampal dentate gyrus do not produce global changes in
      behavior. Results suggest that cholinergic release into the dorsal hippocampus
      facilitates the display of behavioral inhibition at the end of the second
      postnatal week. Behavioral deficits in freezing may reflect an oxotremorine
      induced disruption of hippocampal cholinergic function underlying the processing
      of biologically relevant olfactory stimuli as well as mechanisms associated with
      attention.

PMID- 8883878
TI  - Dendritic arbors of neurons from different regions of the rat thalamic reticular
      nucleus share a similar orientation.
AB  - Neurons in different regions of the rat thalamic reticular nucleus were labeled
      with biotin dextran amine and reconstructed. When viewed in coronal section, some
      neurons had a radial dendritic tree while others had dorso-ventrally elongated
      arbors. When rotated, all the neurons had a planar, disc-shaped dendritic field
      with the dendrites orientated parallel to the long axis of the nucleus. We
      conclude that all thalamic reticular nucleus neurons have a similar dendritic
      morphology and orientation.

PMID- 8883879
TI  - Tracing the auditory pathways to electrophysiologically characterized neurons
      with HRP and Fos double-labeling technique.
AB  - By combining HRP histochemistry with Fos immunocytochemistry, we demonstrate in
      this study that electrophysiologically characterized auditory neurons can be
      double-labeled with HRP and Fos after iontophoretic injection of HRP into the
      recording site. Neurons which projected fibers to the recording site were labeled
      with HRP and were Fos-like immunoreactive. This double-labeling technique in
      combination with electrophysiological recording offers the possibility to
      determine the fiber projections between sound-activated neurons which are
      identified either electrophysiologically and/or immunocytochemically.

PMID- 8883880
TI  - Age-related increase in oxidized proteins in mouse synaptic mitochondria.
AB  - Since it has been proposed that oxidized protein accumulation plays a critical
      role in brain aging, we have investigated their contents in synaptic mitochondria
      from five age groups of mice. Protein carbonyl content in synaptic mitochondria
      showed a significant positive correlation with age (r = 0.95, P = 0.01). A linear
      inverse relationship was observed between protein carbonyl content and complex
      IV/complex I ratio (which was used as an index of imbalance between mitochondrial
      respiratory complexes) in synaptic mitochondria in the five age groups (r = 
      0.99, P < 0.001). We suggest that age-related accumulation of oxidized proteins
      in synaptic mitochondria may be the result of an age-dependent increase in
      reactive oxygen species generation because of a disarrangement of mitochondrial
      oxidative phosphorylation.

PMID- 8883881
TI  - Reversion of beta 25-35-amyloid peptide-induced amnesia by NMDA receptor
      associated glycine site agonists.
AB  - The effects of D-cycloserine (DCS), a N-methyl-D-aspartate receptor-associated
      glycine site agonist, and milacemide (MIL), a glycine prodrug, were examined on
      learning impairments induced by administration of beta 25-35-amyloid peptide (3
      nmol i.c.v.). Mice were examined for spontaneous alternation and step-down
      passive avoidance, 7 and 14 days after beta 25-35, respectively. The beta 25-35
      induced deficits were reversed by DCS, 1-30 mg/kg i.p., or MIL, 3-100 mg/kg i.p.,
      each drug being ineffective on control mice behaviours. These observations
      strengthen the therapeutic potential of glycine site agonists against the memory
      impairments induced by beta-amyloid peptides.

PMID- 8883882
TI  - Pyroglutamyl peptidase I levels and their left-right distribution in the rat
      retina and hypothalamus are influenced by light-dark conditions.
AB  - To evaluate the effects of light and darkness on pyroglutamyl peptidase I
      activity (pGluPI) and its left-right distribution, pGluPI was measured
      bilaterally in the retina and hypothalamus under selected light-dark schedules.
      Rats under a 12 h light-dark cycle were divided into four experimental groups.
      After the end of the 12 h dark period, the animals were kept two additional hours
      in darkness (group 1), or light (group 2). After the end of the 12 h light
      period, the animals were kept two additional hours in darkness (group 3), or
      light (group 4). Experiments were done in light or darkness depending on the 2 h
      period. In the retina, a previous 12 h light period led to higher values of
      enzyme activity than dark periods. Left-right predominance, however, depended on
      the previous 2 h period: the light period led to left predominance, whereas right
      predominance was found after the 2 h dark period. In the hypothalamus, a left
      predominance was found only in group 3. These results demonstrate that
      environmental light conditions influence pGluPI activity in the rat retina and
      hypothalamus.

PMID- 8883883
TI  - Basic fibroblast growth factor expression and tenascin C immunoreactivity after
      partial unilateral hemitransection of the rat brain.
AB  - Basic fibroblast growth factor (bFGF) gene expression as well as its
      immunoreactivity were studied after partial unilateral hemitransection of the rat
      brain during a time course of 24 h, 72 h, 7 and 14 days. The mechanical injury
      resulted in a global increase of bFGF gene expression at the 24-h time interval.
      This global increase was seen at the ipsilateral site at the level of the lesion
      as well as rostral to the lesion in the ipsilateral hemisphere. The upregulation
      in bFGF gene expression was in most of the areas investigated due to an
      upregulation in glial cells as seen by means of nonradioactive in situ
      hybridization compared with immunocytochemistry for glial fibrillary acidic
      protein (GFAP). Basic FGF immunoreactivity (IR) was increased around the lesion
      in glial cell nuclei 7 days after the injury. This increase was also detected in
      GFAP positive glial cells surrounding small vessels in the lesioned area.
      Moreover, in the present paper we demonstrate increased tenascin immunoreactivity
      in the lesioned area 7 days after injury. The tenascin IR was increased at the
      edges of the lesion as well as in vessel like structures. The tenascin IR was
      partially codistributed with GFAP IR in the lesioned area. The lesion was also
      characterized by an increase in vimentin IR as well as in laminin IR. It is
      suggested that the observed changes in the expression of bFGF, matrix proteins
      (laminin, tenascin) and intermediate filaments (vimentin) are involved in (a)
      tissue repair, (b) protection of neuronal cells from excitotoxic influences and
      (c) formation of new vessels in the lesioned area.

PMID- 8883884
TI  - Ultrastructural localization of D1 dopamine receptor immunoreactivity in rat
      striatonigral neurons and its relation with dopaminergic innervation.
AB  - We have investigated by immunohistochemistry the cellular and subcellular
      distribution of the D1 dopamine receptor (D1R) in the rat striatonigral complex
      and its relation with the dopaminergic innervation. In the striatum, single pre
      embedding immunoperoxidase and immunogold labeling demonstrate that D1R is mainly
      located on dendritic shafts and spines of spiny dendrites. D1R is also found in
      association with the plasma membrane of half of the perikarya of medium spiny
      neurons. Double labeling experiments allowing the simultaneous detection of D1R
      and of tyrosine hydroxylase (TH) demonstrate that D1R distribution does not match
      dopamine innervation: a majority of the receptors is located at sites distant
      from dopamine profiles and there is no significant D1R enrichment at sites of
      membrane appositions between dopamine and D1R profiles. In the substantia nigra,
      D1R is located at pre-synaptic sites on small diameter axons which are not in
      contact with TH-positive elements, and on terminal boutons forming symmetrical
      synapses on TH-positive or negative dendrites. These data demonstrate abundance
      and wide distribution of D1R at various extrasynaptic sites in the striatum and
      the substantia nigra, bringing strong evidence of anatomical basis for dopamine
      non-synaptic volume transmission in the rat striatonigral complex.

PMID- 8883885
TI  - Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's
      passive avoidance response: a tetrodotoxin functional inactivation study.
AB  - By means of local administration of tetrodotoxin (TTX) fully reversible
      functional inactivation of rat's dorsal hippocampus (DH) was obtained in order to
      define the role of this structure in the memorization of a conditioned passive
      avoidance response (PAR). In Experiment 1, on permanently cannulated animals, TTX
      (10 ng in 1.0 microliter saline) or saline (1.0 microliter) was injected uni- or
      bilaterally in the DH, respectively 1 h before PAR acquisition, immediately after
      PAR acquisition, and 1 h before PAR retrieval, always performed 48 h after the
      acquisition trial. It was shown that both pre-acquisition and pre-retrieval DH
      uni- or bilateral blockades were followed by significant PAR retention
      impairment, while in post-acquisition only the bilateral blockade determined PAR
      retention impairment. In Experiment 2, on three different groups of rats, TTX (10
      ng in 1 microliter) saline) was bilaterally administered, under general ketamine
      anesthesia (100 mg/kg), into the DH at different post-acquisition delays (0.25,
      1.5, 6 h). Retrieval testing, 48 h after treatment, showed that post-acquisition
      bilateral DH blockade caused PAR impairment only when performed 0.25 or 1.5 h
      after acquisition. The results indicate a well defined mnemonic role of DH during
      the acquisition, consolidation and retrieval of PAR engram. The experimental
      evidence is discussed in relation to other reports and to DH connectivity with
      the medial septal area and the amygdala.

PMID- 8883886
TI  - Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in
      homosynaptic long-term depression of the rat hippocampus.
AB  - Low-frequency stimulation is associated with long-term depression (LTD) of
      synaptic efficacy in various brain structures. Like long-term potentiation (LTP),
      homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor
      activation, changes in postsynaptic calcium concentration and phospholipase A2
      (PLA2) activation. Arachidonic acid (AA) is released after the activation of
      calcium-dependent phospholipases and free AA is rapidly metabolized to a family
      of bioactive products (the eicosanoids) which are thought to be both
      intracellular and extracellular messengers. In the present study, we investigated
      the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism
      in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz
      for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal
      slices. LTD induction was partially blocked by bromophenacyl bromide (50-100
      microM), a selective PLA2 inhibitor, and by the a nonselective lipoxygenase
      inhibitor nordihydroguaiaretic acid (NDGA; 100 microM). In contrast, the specific
      cyclooxygenase blocker indomethacin (100 microM) did not significantly reduce
      hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether
      specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD
      expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50
      microM reduced LTP formation when given in the bath, an effect that was less
      pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the
      activation of endogenous PLA2 and the formation of 12-lipoxygenase metabolites of
      AA may be important factors controlling the expression of hippocampal LTD.

PMID- 8883887
TI  - Effect of low and high doses of nitrous oxide on preproenkephalin mRNA and its
      peptide methionine enkephalin levels in the hypothalamus.
AB  - The effect of exposure to nitrous oxide (N2O) on the levels of preproenkephalin
      mRNA in the hypothalamus of rats was examined. In the first experiment, rats were
      exposed to 1000 ppm N2O for 8 h a day over 4 days. Compared with controls (which
      were exposed to air over the same duration), the N2O exposed animals exhibited
      significant elevations in preproenkephalin mRNA levels in the hypothalamus. In a
      second experiment, rats were exposed to 60% N2O or air for 12, 24 and 48 h
      duration, and hypothalamic levels of preproenkephalin mRNA as well as methionine
      enkephalin were analyzed. Compared with controls, N2O exposed rats exhibited
      significant elevations in preproenkephalin mRNA levels. The levels on
      preproenkephalin mRNA were significantly higher after 48 h of N2O exposure than
      after 12 h of N2O exposure. Similarly, the concentration of methionine enkephalin
      was significantly higher after 24 and 48 h of exposure of N2O than after exposure
      to 12 h of N2O or air. These results indicate that (a) exposure to N2O results in
      significant elevations in preproenkephalin mRNA levels, (b) the increased
      preproenkephalin mRNA levels appear to be proportional to the concentration of
      N2O exposure as well as the duration of N2O exposure, and (c) N2O-induced
      elevation in preproenkephalin mRNA levels is associated with corresponding
      increase in tissue concentrations of methionine enkephalin. In total, these
      results suggest that N2O selectively stimulates synthesis of methionine
      enkephalin in the diencephalic region of the brain.

PMID- 8883888
TI  - Brain cell membrane Na+,K(+)-ATPase activity following severe hypoxic injury in
      the newborn piglet.
AB  - This study tests the hypothesis that severe brain hypoxia causes decreased
      Na+,K(+)-ATPase activity, resulting in permanent alterations in the neuronal cell
      membranes. Seventeen anesthetized piglets (normoxic control (NC), no recovery
      after hypoxia (Group 1), 6 h normoxic recovery (Group 2), and 48 h normoxic
      recovery (Group 3)) were studied. Hypoxia was induced by lowering the FiO2 to
      maintain PCr/Pi ratio at 25% of baseline for 1 h as monitored by 31P-NMR
      spectroscopy. PCr/Pi returned to 57% of baseline by 6 h and was normal by 48 h.
      At termination, cortical tissue Na+,K(+)-ATPase activity was determined. Na+,K(+)
      ATPase activity was measured in cortical membrane preparations by determining the
      rate of ATP hydrolysis. NC membranes had Na+,K(+)-ATPase activity of 58.3 +/- 1.3
      microM Pi/mg protein/h (mean +/- S.E.M.). Na+,K(+)-ATPase activity was reduced in
      Groups 1, 2, and 3 (45.8 +/- 1.3, 47.4 +/- 3.6, 48.7 +/- 2.9 microM Pi/mg
      protein/h) (P < 0.05 compared to NC). There was no difference in enzyme activity
      among Groups 1, 2, or 3. The data show that in spite of recovery of neuronal
      oxidative phosphorylation (PCr/Pi) by 48 h, there is a permanent decrease in
      Na+,K(+)-ATPase activity in cells that have undergone severe hypoxic injury. The
      persistent decrease in Na+,K(+)-ATPase activity indicates ongoing cell injury
      following severe cerebral hypoxia, and that recovery of oxidative phosphorylation
      as indicated by PCr/Pi values cannot be used as an index of recovery of cell
      function.

PMID- 8883889
TI  - Monoethylcholine as a false transmitter precursor at the frog and mouse
      neuromuscular junctions.
AB  - Monoethylcholine (MECH) enters motor nerve terminals where it is made into
      acetylmonoethylcholine (AMECH). AMECH opens endplate channels for about half of
      the average duration observed where they are opened by acetylcholine (ACH).
      Therefore when AMECH is present in a quantum the endplate currents decay more
      rapidly. MECH has been used to measure quantal turnover in motor nerve terminals.
      We find that the incorporation of AMECH into quanta is blocked by vesamicol, an
      inhibitor of ACH transport into synaptic vesicles. AMECH is incorporated more
      rapidly when acetylcholinesterase is inhibited, when the choline uptake
      inhibitor, hemicholinium-3, is present or when extracellular Na+ (required for
      active CH uptake) is replaced with methylamine. This suggests that in the absence
      of these inhibitors CH obtained from released ACH is recycled. Therefore,
      experiments on the rate of incorporation of MECH are misleading unless CH
      recycling is prevented. Previous work also suggested that MECH is incorporated at
      a faster rate into those quanta which are released by stimulation than into those
      released spontaneously. We conclude that quanta released spontaneously and
      following nerve stimulation probably come from the same pool. The distribution of
      t1/2's during the incorporation of MECH can be accounted for in the framework of
      recent studies of the recycling of synaptic vesicles. We conclude that false
      transmitter is a valuable tool for studying the loading of quanta, but that there
      are several complications to be considered when trying to use it to measure the
      turnover of the population of quanta.

PMID- 8883890
TI  - Dexamethasone and forskolin synergistically increase [Met5]enkephalin
      accumulation in mixed brain cell cultures.
AB  - Possible synergistic effects of the glucocorticoid dexamethasone (DEX, 10(-7) M)
      and the adenylate cyclase agonist forskolin (FSK, 10(-5) M) on [Met5]enkephalin
      (ME) accumulation were examined in enriched rat glial cultures and in mixed
      neuronal/glial cultures. In enriched glial cultures, DEX and FSK each stimulated
      the accumulation of ME 2-3-fold over basal media levels, but there was little
      additional stimulation when these agonists were combined. In contrast, mixed
      neuronal/glial cultures showed only weak responses to DEX or FSK alone, but the
      combination of these agonists produced a pronounced synergistic effect on media
      ME accumulation (6-10-fold over basal levels). The DEX effect was mediated via a
      classical glucocorticoid receptor, since DEX was potent (acting over a
      concentration range of 10(-11)-10(-7) M), mimicked by corticosterone (10(-6) M),
      and blocked by the glucocorticoid receptor antagonist RU486. There was a
      pronounced time lag (2 days) for the synergistic effects of DEX + FSK to develop.
      In situ hybridization and immunocytochemical studies suggested that astrocytes
      were the major source for the increased ME production in all mixed neuronal/glial
      cultures examined. Creating a mixed culture by plating fetal neurons onto
      confluent, enriched P7 glial cultures inhibited accumulation of ME in the media.
      DEX + FSK, but neither agonist alone, overcame this neuronal inhibition and
      increased accumulation of media ME to levels identical to levels in stimulated
      enriched glial cultures. The net effect was a 6-fold increase in ME accumulation
      in the mixed neuronal/glial cultures relative to a 2.5-fold increase in the
      enriched glial cultures. Neuronal inhibition of basal glial ME production could
      explain the similar synergistic effects of DEX + FSK observed in all mixed
      neuronal/glial cultures examined, and may be important in suppressing ME
      production by astrocytes in the brain.

PMID- 8883891
TI  - The organisation of dendritic bundles in the prelimbic cortex (area 32) of the
      rat.
AB  - Using an antibody against microtubule associated protein 2 (MAP-2; a specific
      marker for neuronal dendrites), this paper reports the structural organisation of
      pyramidal cell apical dendrites in the rat prelimbic (PL) cortex. In the coronal
      plane, MAP-2-immunoreactive apical dendrites of pyramidal neurons in layers 5, 3
      and 2 were found bundled together as they ascended radially through the cortex.
      These bundles of dendrites dispersed in upper layer 2 to form apical dendritic
      tufts in layer 1. In tangential cross-section, the immunolabelled bundles were
      organised into a latticework of discrete clusters of differentially sized
      profiles. At the boundary between layers 3 and 5, clusters were composed of 26 +/
      8 dendritic profiles (group mean value +/- S.D., five animals), whereas clusters
      in layer 2 contained 55 +/- 15 profiles. The number of clusters per unit surface
      area was not significantly different throughout layers 5, 3 and 2 (760 +/- 75 per
      mm2) with the average centre-to-centre intercluster distance in these layers
      being 44.2 +/- 4.9 microns. The data indicate that apical dendritic bundles are a
      feature of the radial organisation of PL cortex. These structural subunits may
      subserve specific integrative functions in the PL area of the rat medial
      prefrontal cortex.

PMID- 8883892
TI  - Effects of energy deprivation induced by fluorocitrate in immortalised rat brain
      microvessel endothelial cells.
AB  - The effects of the mitochondrial aconitase inhibitor, fluorocitrate on the
      immortalised rat brain endothelial cell line (RBE4) were investigated. Treatment
      with different concentrations of fluorocitrate (0-1 mM) for 24 h induced a
      significant, concentration-dependent decrease in the MTT reduction (an index of
      mitochondrial function), intracellular ATP content, glucose consumption and
      lactate production by RBE4 cell monolayers but did not alter the glucose to
      lactate ratio at concentrations lower than 0.5 mM. At all concentrations,
      fluorocitrate induced a significant decrease in the protein content per well.
      Fluorocitrate treatment of confluent RBE4 cells induced a marked redistribution
      of the F-actin cytoskeleton from a characteristic marginal band to a more diffuse
      cytosolic pattern. This redistribution of the cytoskeleton coincided with a
      reduction in the total cellular F-actin content of the RBE4 cells at
      fluorocitrate concentrations greater than 0.5 mM. Treatment of confluent RBE4
      cells with fluorocitrate had no significant effect on RBE4 cell monolayer
      permeability measured by FITC-dextran or [14C]sucrose. These results show that
      whilst energy deprivation following fluorocitrate treatment induces significant
      changes in the RBE4 cell F-actin cytoskeleton and cellular metabolism, it does
      not have any significant effect on endothelial cell monolayer permeability. These
      results demonstrate that profound toxic effects on endothelial cell structure and
      metabolism are not necessarily accompanied by changes in endothelial cell
      monolayer permeability.

PMID- 8883893
TI  - SC1, a brain extracellular matrix glycoprotein related to SPARC and follistatin,
      is expressed by rat cerebellar astrocytes following injury and during
      development.
AB  - In the nervous system, extracellular matrix components are believed to influence
      cell shape, proliferation and migration during development and following injury.
      SC1 is a secreted glycoprotein expressed during neural development and in the
      adult brain. The molecule shows partial sequence homology to the anti-adhesive
      extracellular matrix molecule SPARC/osteonectin and to follistatin. We have made
      a surgical lesion in the adult rat cerebellum and examined changes in SC1
      expression at 1 to 14 days after injury. Dual in situ
      hybridization/immunohistochemistry demonstrated that SC1 mRNA was induced in
      astrocytes surrounding the wound, reaching maximal levels at 10 days post-lesion.
      Immunohistochemistry revealed changes in the deposition of SC1 protein in radial
      fibres of Bergmann glia. SC1 protein was also detected at the border of the
      lesion, suggesting an association with the glial scar. Double
      immunohistochemistry with the astrocytic marker GFAP demonstrated that astrocytes
      also express SC1 during postnatal development.

PMID- 8883895
TI  - Electron microscopic study of GABAergic synaptic innervation of neurotensin
      immunoreactive neurons in the dorsal raphe nucleus.
AB  - A double immunocytochemical method combining the preembedding avidin-biotin
      peroxidase-complex technique and the postembedding immunogold technique was used
      to examine synaptic interactions between GABAergic and neurotensin-containing
      neurons in the same tissue sections of the dorsal raphe nucleus of the rat.
      Whereas the neurotensin-like immunoreactive perikarya rarely received synapses
      from GABA-like immunostaining axon terminals, the neurotensin-like immunoreactive
      dendrites frequently received synapses from GABA-like immunoreactive neurons.
      These results suggest that GABAergic neurons could modulate neurotensinergic
      neurons in the dorsal raphe nucleus through synaptic relations. The
      immunocytochemically identified local synaptic circuit in the dorsal raphe was
      discussed.

PMID- 8883894
TI  - Cyclosporin A, an inhibitor of calcineurin, impairs memory formation in day-old
      chicks.
AB  - Considerable evidence exists that changes in the phosphorylation state of
      neuronal proteins are correlated with learning and that inhibition of various
      protein kinases disrupts memory formation. Given the reversible nature of protein
      phosphorylation, a role for protein phosphatases in memory processing also seems
      likely. It has been shown recently that administration of the phosphatase
      inhibitor, okadaic acid, disrupts memory formation in day-old chicks, with
      retention deficits first appearing at approximately 40 min post-training [93]. In
      the present study the intracranial administration of the immunosuppressant
      cyclosporin A was also found to produce retention deficits in day-old chicks
      trained on a single-trial, passive-avoidance task, but the deficits were not
      significant until 85 min post-training. The difference could not be attributed to
      differences in the pharmacokinetics of the drugs. Since okadaic acid
      preferentially inhibits protein phosphatases 1 and 2A, while cyclosporin A is
      reported to inhibit only the Ca2+/calmodulin-dependent protein phosphatase,
      calcineurin, it is possible that different phosphatases may be involved in
      distinct stages of memory formation, as has been reported previously for protein
      kinases. The possibility that cyclosporin A may, in addition, act through
      inhibition of cyclophilin's peptidyl-prolyl-cis/transisomerase activity is also
      canvassed.

PMID- 8883896
TI  - High-resolution fluorescent labeling of living cerebellar slices.
AB  - In the present study, we extend previous research on staining of living brain
      slices with fluorescent phospholipids. This new procedure allows high-resolution
      staining of specific cell types, in particular, Purkinje cells, in the cerebellar
      slice while not affecting the intrinsic electrical activity of the tissue. Four
      different nitrobenzoxadiole (NBD)-phospholipids were incorporated into living
      cerebellar slices via loading from small unilamellar vesicles (SUVs), composed of
      a carrier and the fluorescent lipid. The labeled acidic phospholipid, NBD
      phosphatidic acid (NBD-PA), produced the highest resolution images with exquisite
      labeling of the dendritic fields. The label was incorporated predominantly into
      the Purkinje cell body (excluding the nucleus), with more diffuse staining in
      other cell types, including stellate, basket and granule cells. The labeled lipid
      concentration and composition of the carrier lipid were significant in
      determining the specificity of labeling. Labeling, which was optimal after a 1 h
      incubation, was present throughout the depth of the slice. This procedure
      provides a promising approach to fluorescent labeling that will allow
      simultaneous monitoring of changes in cellular morphology and electrophysiology
      of living brain slices.

PMID- 8883897
TI  - Nicotine injections into the ventral tegmental area increase locomotion and Fos
      like immunoreactivity in the nucleus accumbens of the rat.
AB  - Systemic administration of nicotine has been shown to increase locomotor activity
      in rats, an effect which is enhanced by chronic pretreatment with the drug.
      Furthermore, administration of nicotine either systemically, or locally within
      the ventral tegmental area (VTA), increases extracellular levels of dopamine (DA)
      in the nucleus accumbens (NAc). In the present study, we examined the effect of
      local, bilateral injections into the VTA of nicotine (0.02, 0.2, 2.0 and 8.0
      micrograms/0.5 microliter/side) on locomotor activity of rats in an open field.
      Nicotine (8.0 micrograms/side) significantly increased forward locomotion within
      20 min after injection, whereas rearing was not affected. The stimulatory effect
      of locally applied nicotine was completely blocked by pretreatment with
      mecamylamine (1.0 mg/kg, s.c.). Repeated intra-tegmental injections of a
      subthreshold dose of nicotine (2.0 micrograms/side every 2 days), gradually
      increased locomotion, compared to the effect of acute intra-tegmental
      administration or control injections of saline, after the fifth and sixth
      injection. The effects of intra-tegmental injections of nicotine were further
      investigated on cells in several target areas for the VTA-DA neurons through
      determination of c-fos expression by means of Fos immunohistochemistry. Intra
      tegmental injections of nicotine (8.0 micrograms/side) increased Fos-like
      immunoreactivity in the NAc, but did not affect the number of Fos-positive nuclei
      in the medial prefrontal cortex or in the dorsolateral striatum. The increase in
      accumbal Fos-like immunoreactivity was attenuated by pretreatment with
      mecamylamine (1.0 mg/kg, s.c.). Our data demonstrate that locomotor activating
      effects similar to those evoked by systemically administered nicotine, including
      behavioral sensitization, can be produced by intra-tegmental nicotine
      administration. Moreover, such local VTA administration of the drug was found to
      significantly affect neurons within DA target areas. Our findings support the
      notion that the effects of systemically administered nicotine in mesolimbic
      target areas are largely dependent on stimulation of nicotinic receptors in the
      VTA.

PMID- 8883898
TI  - Thyrotropin-releasing hormone (TRH) attenuates glutamate-stimulated increases in
      calcium in primary neuronal cultures.
AB  - Thyrotropin-releasing hormone (TRH) has been found to be widely distributed in
      the mammalian central nervous system. Further, the concentration of the
      tripeptide increases following seizure activity, and TRH is known to have
      anticonvulsant effects. We have investigated the possibility that the
      anticonvulsant activity of TRH may be due, at least in part, to an attenuation of
      the glutamate-stimulated increases in intraneuronal Ca2+ ([Ca]i) that occur with
      epileptic activity. We find that the tripeptide does not itself excite neurons
      and that it is able to significantly reduce glutamate-stimulated increases in
      [Ca]i in cultured neurons derived from fetal rat forebrain. Increases in the
      concentration of TRH following seizure activity may represent an endogenous
      homeostatic mechanism for reducing glutamate-induced elevations in intraneuronal
      Ca2+.

PMID- 8883899
TI  - Mechanisms of glutamate and aspartate release in the ischemic rat cerebral
      cortex.
AB  - Elevated levels of glutamate and aspartate have been implicated in the
      pathogenesis of neural injury and death induced by ischemia. The mechanism(s)
      whereby they escape into the extracellular environment have been a subject of
      controversy. This study evaluated the contribution of phospholipases and protein
      kinases to ischemia-evoked glutamate and aspartate release from the
      ischemic/reperfused rat cerebral cortex. Changes in the extracellular levels of
      these amino acids during four-vessel occlusion elicited global cerebral ischemia
      were examined using a cortical cup technique. Ischemia-evoked amino acid release
      was compared in control vs. drug treated animals, in which selective inhibitors
      of phospholipases and protein kinases were applied topically onto the cerebral
      cortex. The phospholipase inhibitors tested included 4-bromophenacyl bromide, a
      non-selective inhibitor; 7,7-dimethyleicosadienoic (DEDA), an inhibitor of
      secretory type phospholipase A2 (PLA2); AACOCF3, an inhibitor of the Ca2(+)
      dependent cytoplasmic form of PLA2, HELSS, which inhibits a Ca(2+)-independent
      cytoplasmic PLA2, and U73122, a selective inhibitor of phospholipase C (PLC). All
      five phospholipase inhibitors significantly attenuated glutamate and aspartate
      release into the extracellular milieu, indicating the possibility that several
      forms of the enzyme are likely to be involved. The protein kinase C (PKC)
      inhibitor, chelerythrine chloride, also reduced excitatory amino acid efflux,
      wheres the PKC activator phorbol 12-myristate 13-acetate (PMA) enhanced their
      release. The non-selective kinase inhibitor, staurosporine, and H-89, which
      selectively inhibits protein kinase A, did not reduce ischemia-evoked amino acid
      efflux. These results suggest that ischemia-evoked release of the excitatory
      transmitters amino acids is a result, in part, of the activation of
      phospholipases A2 and C, with PKC involvement in the transduction process.
      Destabilization and deterioration of the plasma membrane, as a consequence of
      phospholipid hydrolysis, may allow these transmitter amino acids to diffuse down
      their concentration gradients into the extracellular fluid.

PMID- 8883900
TI  - Down-regulation of rat brain 5-HT uptake carriers after treatment with high doses
      of D-fenfluramine.
AB  - Male rats were treated with 10 mg/kg D-fenfluramine (DF) i.p., twice a day for 4
      days. Five days later there was a strong reduction (70-100%) in the Bmax of
      [3H]citalopram binding and the Vmax of [3H]5-HT uptake in cortical and
      hippocampal synaptosomes; 2 months after the treatment these parameters were
      reduced by 40-70%. The effect of treatment was also evaluated in synaptosomes
      preloaded with [3H]5-HT, superfused and exposed for 3 min to a releasing stimulus
      (15 mM K+ or 0.5 microM DF). In our experimental conditions, the stimulated [3H]5
      HT release is Ca(2+)-dependent and takes place only from 5-HT nerve endings. The
      K(+)-stimulated release was not consistently altered by the DF treatment whereas
      DF-stimulated [3H]5-HT release was markedly reduced, either 5 days and 2 months
      after the treatment. The effect of chronic DF was different from the effect of
      i.c.v. 5,7-DHT, a specific 5-HT neurotoxin which completely abolished the K(+)
      induced release. Since the decrease of synaptosomal [3H]5-HT uptake induced by
      5,7-DHT (82%) was similar to that found after chronic DF (70-80%), these data
      suggest that the decrease of 5-HT uptake sites induced by chronic DF is not
      (only) due to neurodegeneration. That chronic DF could induce a functional down
      regulation of 5-HT uptake sites (i.e. decreased density per intact nerve ending)
      was suggested by the decrease of DF-induced release, since the releasing activity
      of DF is dependent on functional 5-HT uptake sites. However, due to the
      characteristics of our model, our results are compatible with either the absence
      or the presence of a concomitant, partial neurodegeneration of 5-HT nerve endings
      in DF-treated rats. In summary, our data indicate that after treatment with high
      doses of DF, the 5-HT uptake carriers undergo a long-lasting down-regulation,
      thus totally or partly explaining the lower [3H]citalopram binding and the lower
      synaptosomal [3H]5-HT uptake.

PMID- 8883901
TI  - Telencephalic afferents to the caudolateral neostriatum of the pigeon.
AB  - The pigeon caudolateral neostriatum (NCL) shares a dopaminergic innervation with
      mammalian frontal cortical areas and is implicated in the regulation of avian
      cognitive behavior. Retrograde tracing methods were used to identify forebrain
      projections to NCL and to suggest a possible role of this area in mediating
      spatial behavior. NCL receives telencephalic projections from the hyperstriatum
      accessorium, cells along the border of hyperstriatum dorsale and hyperstriatum
      ventrale, anterolateral hyperstriatum adjacent to the vallecula, confined cell
      groups within the anterior neostriatum, and subdivisions of the archistriatum. In
      addition, labeling of a small number of large cells near the fasciculus
      prosencephali lateralis was observed at the level of the anterior commissure. In
      accordance with previous studies, projections of subtelencephalic areas were
      revealed to originate from the thalamic posterior dorsolateral nucleus and
      nucleus subrotundus, as well as from the tegmental nucleus pedunculopontinus and
      locus coeruleus. Forebrain connections of NCL show that somatosensory, visual,
      and olfactory information can combine in this division of the neostriatum. NCL is
      therefore suited to participate in a neural circuit that regulates spatial
      behavior. Moreover, the present study reveals that NCL is reached by a limbic
      projection from the nucleus taeniae. This projection also suggests similarity
      between NCL and mammalian frontal cortical areas.

PMID- 8883902
TI  - Ethanol inhibits chemoreflex excitation of reticulospinal vasomotor neurons.
AB  - In anesthetized and ventilated rats, activation of carotid chemoreceptors with
      intracarotid administration of 100 nmol sodium cyanide rapidly excited the spinal
      cord-projecting vasomotor neurons in the rostroventrolateral reticular nucleus
      (RVL) of the medulla oblongata and sympathetic nerves and increased arterial
      pressure. The chemoreflex sympathoexcitatory pressor responses were attenuated by
      an acute systemic administration of ethanol at 0.45 g/kg, but not at 45 mg/kg.
      The ethanol effects were observed at the level of RVL-spinal vasomotor neurons,
      in attenuating the neuronal responses to the chemoreflex excitation and direct
      iontophoresis of N-methyl-D-aspartic acid (NMDA) but without altering responses
      of the carotid sinus nerves to intracarotid cyanide. The effect of ethanol on the
      RVL neurons was further defined as blocking NMDA-evoked inward current in the
      corresponding spontaneously active RVL neurons in vitro. The results indicate
      that acute ethanol intoxication markedly influences NMDA receptor activation and
      arterial chemoreflexes. The relevance of the type of action to clinical
      hypertension in chronic and heavy drinkers is discussed.

PMID- 8883903
TI  - Effect of up-regulation of NMDA receptors on cerebral O2 consumption and blood
      flow in rat.
AB  - We tested the hypothesis that cerebrocortical blood flow and O2 consumption would
      be proportional to an up-regulated number of functional N-methyl-D-aspartate
      (NMDA) receptors. Previous work had shown a relationship between cerebral
      metabolism and NMDA receptor activity. We increased the specific binding to NMDA
      receptors in the cerebral cortex, from 2.2 +/- 0.9 to 4.5 +/- 0.8 (density units)
      in male Long-Evans rats by daily giving two intraperiotoneal injections (30
      mg/kg) of CGS-19755, an NMDA receptor inhibitor, for 7 consecutive days
      (discontinued for 20 h before experiment). Twelve up-regulated (CGS treated) and
      12 control rats were used in this study. Under isoflurane anesthesia and after
      topical stimulation of the right cerebral cortex with 10(-2) M NMDA, the blood
      flow (14C-iodoantipyrine method) increased from 98 +/- 11 ml/min/100 g in the
      unstimulated cortex of the control rats to 161 +/- 37 ml/min/100 g in the
      stimulated cortex. The unstimulated value for blood flow (95 +/- 7 ml/min/100 g)
      did not change in the upregulated group but it doubled (194 +/- 69 ml/min/100 g)
      in the stimulated, upregulated cortex. Similarly, O2 consumption
      (cryomicrospectrophotometrically determined) in normal rats increased 46%, from
      9.3 +/- 1 ml/min/100 g to 13.6 +/- 4 after NMDA stimulation. While in the
      upregulated animals, O2 consumption increased 103% from 7.9 +/- 0.6 to 16 +/- 6.5
      after NMDA stimulation. In conclusion, NMDA receptor upregulation does not alter
      basal cerebrocortical blood flow or O2 consumption but in the NMDA-stimulated
      cortex, the blood flow and O2 consumption increase is dependent on the number of
      NMDA receptors present.

PMID- 8883904
TI  - Local injection of kainic acid causes widespread degeneration of NADPH-d neurons
      and induction of NADPH-d in neurons, endothelial cells and reactive astrocytes.
AB  - Nitric oxide (NO), a diffusible gas, is a messenger molecule that mediates
      vascular dilatation and neural transmission. The enzyme nitric oxide synthase
      (NOS) present in neurons is activated by Ca2+ influx associated with activation
      of glutamate receptors. Cultured cortical neurons containing NOS are selectively
      vulnerable to injury by kainic acid (KA). However, the relationship between NOS
      neurons and excitotoxicity under in vivo conditions is not entirely clear. In the
      present study, we examined the time course and spatial distribution of changes in
      NOS neurons caused by an intracortical microinjection of KA in adult rats. NADPH
      diaphorase (NADPH-d) histochemistry was used as a marker for NOS and the neuronal
      changes were correlated with changes in glial cells and endothelial cells. We
      demonstrated a rapid loss of NADPH-d neurons in the lesion center and
      degeneration of NADPH-d neurons and nerve terminals throughout ipsilateral cortex
      and hippocampus; the striatal neurons appeared to be unaffected. Subsequent to
      cortical neuronal degeneration, new NADPH-d activity appeared in proliferative
      reactive astrocytes and in endothelial cells at lesion periphery, and in neuronal
      groups at lesion periphery, in ipsilateral entorhinal cortex and bilateral
      hippocampus. These findings indicate that neurons expressing NADPH-d in cerebral
      cortex and hippocampus are selectively vulnerable to KA toxicity in vivo. The
      subsequent induction of NOS in neural and non-neural cells may be regarded as an
      adaptive response to the kainate-induced brain lesion.

PMID- 8883905
TI  - Cholecystokinin octapeptide reverses the kappa-opioid-receptor-mediated
      depression of calcium current in rat dorsal root ganglion neurons.
AB  - Although the cholecystokinin octapeptide (CCK-8) is reported to antagonize the
      kappa-opioid-receptor-mediated analgesic effect in spinal cord, its mechanism and
      sites of action remain obscure. In the present study, the whole-cell patch-clamp
      recording technique was employed to examine the effect of kappa-opioid agonist
      U50488H on voltage-gated calcium channels and the interaction between the CCK-8
      and U50488H in acutely isolated rat dorsal root ganglion neurons. The results
      indicate that the calcium currents elicited in dorsal root ganglion neurons can
      be depressed by U50488H, an effect readily reversed by the kappa-opioid receptor
      antagonist Nor-BNI or by the antiopioid peptide CCK-8. The effect of the CCK-8
      can be abolished by the CCK-B receptor antagonist, L365,260. While CCK-8 showed a
      potent opioid-reversal effect, it by itself exerted a slight inhibitory effect on
      calcium current. This novel observation in the dorsal root ganglion neurons
      indicates that CCK-8 can antagonize the kappa-opioid-receptor-mediated depressant
      effect on voltage-gated calcium current, and this antagonizing effect appears to
      be mediated via CCK-B receptor.

PMID- 8883906
TI  - Re-examination of the local control by nerve growth factor of the outgrowth of
      neurites in PC12D cells.
AB  - We have examined the local control by nerve growth factor (NGF) of the outgrowth
      of neurites from clonal cells, PC12D, a subline whose phenotype resembles that of
      the parent PC12 cell line in the NGF-primed state. We show here that (i) the
      outgrowth of neurites, and their survival can be induced by NGF in enucleated
      PC12D cells (ii) individual neurites of a single 'giant cell', produced by cell
      fusion of PC12D cells, can respond independently to the NGF in the local
      environment, (iii) dissected neurites from giant cells survive for longer in
      medium that contains NGF than in medium that does not, (iv) in PC12D cells, the
      rapid formation of ruffles in response to NGF, which appears to be based on
      increased cell-substratum adhesion, leads to the subsequent formation of
      neurites, and (v) upon addition of NGF, the movement of short processes displaces
      polylysine-coated beads in the vicinity of neurites. These observations suggest
      that the NGF-dependent maintenance or extension of neurites might be controlled
      within the neurites themselves and might not require the direct involvement of
      the cell body, even in PC12 cells. It seems possible that any NGF-induced changes
      that promote an increase in cell-substratum adhesion might be responsible for the
      initiation and elongation of neurites. It also seems possible that the growth of
      neurites towards a source of NGF might be based on repeated rounds of extension
      and retraction of filopodia and neurites in a manner that depends on the
      concentration of NGF.

PMID- 8883907
TI  - Sparse distribution of NADPH diaphorase neurons in the hippocampal formation of
      the inbred mutant strain EL mouse.
AB  - The number of NADPH diaphorase-positive cells in the CA1/CA2 and CA3 regions of
      Ammon's horn and the subiculum of the hippocampal formation of EL mice, an inbred
      mutant strain of the ddY mouse susceptible to convulsive seizures, was fewer than
      that of ddY mice. These findings suggest that smaller numbers of nitric oxide
      producing cells in the hippocampal formations of EL mice is related to their
      susceptibility to convulsive seizures.

PMID- 8883908
TI  - Phase-shifting effects of a serotonin agonist in tau mutant hamsters.
AB  - Previous studies indicate that the advance region of the tau mutant hamster's
      phase-response curve (PRC) to non-photic stimuli, such as NPY and wheel pulses,
      is characterized by earlier timing and increased amplitude in comparison with
      that of wild-type animals. Since, recent evidence suggests that serotonergic
      pathways may play an important role for the non-photic phase resetting of the
      rodent circadian pacemaker, PRCs to the serotonin (5-HT) agonist, 8-OH-DPAT (5
      mg/kg i.p), were generated in both wild-type and tau mutant hamsters kept in
      constant darkness. The results indicate that the tau mutation is associated with
      changes in the timing, but not the amplitude of the advance region of the PRC to
      8-OH-DPAT and suggest that serotonergic agents and other non-photic or activity
      inducing stimuli may share some common mechanisms for resetting the phase of the
      rodent circadian pacemaker.

PMID- 8883909
TI  - Sparing of striatal neurons coexpressing calretinin and substance P (NK1)
      receptor in Huntington's disease.
AB  - Immunohistochemical studies of the striatum in normal human subjects with a
      double-antigen localization method have revealed the presence of large and medium
      sized aspiny neurons displaying immunoreactivity for both the calcium-binding
      protein calretinin and substance P (neurokinin-1) receptor. These large and
      medium-sized cells from two distinct classes of striatal interneurons, which
      together represent less than 3% of the total neuronal population of the human
      striatum. Observations made in four cases of Huntington's disease revealed that
      such doubly labeled interneurons are still present in the striatum of these
      patients, despite the marked atrophy of the structure. This study provides the
      first evidence for the existence of interneurons containing calretinin and
      expressing tachykinin receptors in the human striatum. It also demonstrates the
      selective sparing of these chemospecific striatal neurons in Huntington's
      disease.

PMID- 8883910
TI  - Nitric oxide synthase is concentrated at the skeletal muscle endplate.
AB  - NO performs a wide array of cell signaling functions. Neuronal NO synthase (nNOS)
      immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NDP)
      activity, a marker of nNOS, were concentrated at adult rat neuromuscular
      junctions and persisted in denervated muscle indicating the localization of the
      enzyme to the postsynaptic surface. The concentration of nNOS at the muscle
      endplate suggests NO could serve as a messenger pre- and postsynapticly.

PMID- 8883912
TI  - Prearcuate cortex in the Cebus monkey has cortical and subcortical connections
      like the macaque frontal eye field and projects to fastigial-recipient oculomotor
      related brainstem nuclei.
AB  - The cortical and subcortical connections of the prearcuate cortex were studied in
      capuchin monkeys (Cebus apella, albifrons) using the anterograde and retrograde
      transport capabilities of the horseradish peroxidase technique. The findings
      demonstrate remarkable similarities to those of the macaque frontal eye field and
      strongly support their homology. The report then focuses on specific prearcuate
      projections to oculomotor-related brainstem nuclei that were shown in a companion
      experiment to entertain connections with the caudal oculomotor portion of the
      cerebellar fastigial nucleus. The principal corticocortical connections of the
      cebus prearcuate cortex were with dorsomedial prefrontal cortex, lateral
      intraparietal sulcal cortex, posterior medial parietal cortex, and superior
      temporal sulcal cortex, which were for the most part reciprocal and columnar in
      organization. The connections of the dorsal prearcuate region were heavier to the
      dorsomedial prefrontal and posterior medial parietal cortices, and those of the
      ventral region were heavier to the superior temporal sulcal cortex. The
      prearcuate cortex projects to several brainstem areas which also receive
      projections from the caudal fastigial nucleus, including the supraoculomotor
      periaqueductal gray matter, superior colliculus, medial nucleus reticularis
      tegmenti pontis, dorsomedial basilar pontine nucleus, dorsolateral basilar
      pontine nucleus, nucleus reticularis pontis caudalis, pontine raphe, and nucleus
      prepositus hypoglossi. The findings define a neuroanatomical framework within
      which convergence of prearcuate (putative frontal eye field) and caudal fastigial
      nucleus connections might occur, facilitating their potential interaction in
      saccadic and smooth pursuit eye movement.

PMID- 8883913
TI  - The development of oxidative metabolism in diencephalic structures of the rat: a
      quantitative study.
AB  - A new method for quantitative determination of cytochrome oxidase (C.O.) activity
      was applied to diencephalic structures of the limbic system that are closely
      connected anatomically, that is, the mammillary bodies (MB) and the anterior
      nucleus of the thalamus (AT). This method makes it possible to easily evaluate
      the oxidative metabolic capacity of brain regions, an index of their
      functionality. By using this technique, we studied the postnatal development of
      both structures in Wistar rats of 14, 21, 30, and 120 days of age. Furthermore,
      animals of 730 days were included in order to evaluate the effects of aging on
      C.O. activity of these structures. The results showed a significant increase in
      the C.O. activity of the subdivisions of the AT, its levels remaining constant
      until the adult age, with a significant decrease in its activity in aged animals.
      In the MB, only the increase in C.O. activity of the medial mammillary nucleus
      (pars medialis) was significant until the adult age. A decrease of C.O. values
      with aging was significant only in the lateral mammillary nucleus. These data
      suggest that there is a wide heterogeneity in the maturation and aging of brain
      oxidative metabolism in diencephalic structures.

PMID- 8883914
TI  - Descending inhibition in neonatal rat spinal cord: actions of pentobarbital and
      morphine.
AB  - Descending inhibition plays an important role in modulating spinal nociceptive
      neurotransmission. Barbiturates have been suggested to be poor analgesics or anti
      analgesic because they block descending inhibition from supraspinal centers to
      the spinal cord. Opiate analgesics, on the other hand, are postulated to increase
      descending inhibition. We tested this hypothesis in an isolated brain stem-spinal
      cord preparation from neonatal rats, using as the test response a nociceptive
      related slow ventral root potential (sVRP) recorded in the lumbar region. Brain
      stem and spinal cord were separately perfused. Transecting the spinal cord,
      applying the local anesthetic lidocaine to the brain stem, or cooling the brain
      stem increased the area of the sVRP, thus demonstrating that tonic descending
      inhibition is present in this preparation. Pentobarbital (Pb) (1-10 microM)
      applied to the spinal cord depressed the sVRP in a dose-dependent fashion. Spinal
      cord transection did not significantly change Pb potency. Pb (5-10 microM)
      applied to the brain stem alone did not significantly increase sVRP amplitude.
      Morphine (15-35 nM) applied to the spinal cord also depressed the sVRP but had no
      effect when applied to the brain stem. The results show that there are functional
      synaptic connections mediating tonic descending inhibition in the neonatal rat.
      They do not support interaction with tonic descending inhibition as an
      explanation for morphine analgesia or as a reason for lack of analgesic
      properties in the barbiturates.

PMID- 8883915
TI  - Lateral habenular influence on dorsal raphe neurons.
AB  - Previously, we have demonstrated that lateral habenula (LH) modulates the
      bioelectric activity of the hippocampus through the dorsal raphe nucleus
      functional involvement. In this study we have, preliminarily,
      electrophysiologically identified two types of raphe neurons: "slow" (S cells,
      serotonergic in nature); and "fast" (F cells, presumably GABAergic in nature).
      Then, we have shown that LH electrical stimulation at lower frequency induced an
      excitation of S and F neurons. LH stimulation at higher frequency inhibited only
      S neurons. Furthermore, iontophoretic NMDA excited S and F neurons. The
      excitatory effects of LH stimulation were antagonized by the iontophoretic 2-APV
      (NMDA antagonist). Iontophoretic GABA inhibited only S neurons. Iontophoretic
      bicuculline antagonized the LH-induced inhibition os S neurons. The data
      suggested a direct (NMDA-mediated) and indirect (through the F GABAergic
      inhibitory interneuron) influence of the LH on the serotonergic efferent neuron.

PMID- 8883916
TI  - Mouse cerebellar GABAB participation in the expression of acute ethanol-induced
      ataxia and in its modulation by the cerebellar adenosinergic A1 system.
AB  - The possible modulation and of co-modulation by the cerebellar GABAB and
      adenosine A1 receptors of ethanol-induced motor impairment were investigated in
      the mice using rotorod performance as the test response. Direct cerebellar
      microinfusion of GABAB agonist, baclofen, and antagonist, phaclofen, into the
      permanently cannulated mice, produced a dose-dependent accentuation and
      attenuation, respectively of ethanol-induced motor impairment. The baclofen and
      phaclofen exhibited accentuation and attenuation, respectively, via GABAB
      receptors linked to pertussis toxin-sensitive G protein. A comodulation by the
      cerebellar adenosine A1 receptors was also observed because intracerebellar
      microinfusion of adenosine agonists NB-cyclohexyladenosine (CHA), 5'-N
      ethylcarbox-amidoadenosine (NECA), and 2-p-(2-carboxyethyl)-phenyl-ethylamino-5'
      N-ethylacarbox- amidoadenosine (CGS-21680), and antagonist, 8-cyclopentyl-1, 3
      dipropylxanthine (DPCPX), also accentuated and attenuated, respectively, ethanol
      induced motor impairment. The accentuation of ethanol-induced motor impairment by
      baclofen was further enhanced after the intracerebellar microinfusion of CHA,
      suggesting a co-modulation by the co-localized adenosine A1 receptors. A similar
      response was observed after the intracerebellar microinfusion of adenosine A1 =
      A2 agonist NECA and the several-fold higher dose of adenosine A2-selective
      agonist CGS-21680. Ethanol-induced motor impairment was markedly blocked by
      intracerebellar A1-selective antagonist, DPCPX, as well as by the intracerebellar
      pertussis toxin pretreatment suggesting again a co-modulation by the adenosine A1
      receptors and the involvement of pertussis toxsin-sensitive G protein,
      respectively. The almost 25-fold higher dose of CGS-21680 to accentuate and DPCPX
      to attenuate, respectively, ethanol-induced motor impairment together with the
      reported cerebellar localization of adenosine A1 subtype only, suggested A1
      receptor activation by NECA and CGS-21680. The functional similarity between
      GABAB and adenosine A1, receptors associated with their anatomical co
      localization on the cerebellar granule cells, mainly axons and axonal terminals,
      may suggest a possible common adenylate cyclase catalytic unit as the basis of
      modulation of ethanol's motor impairment by these two receptor mechanisms.

PMID- 8883918
TI  - The primate motor thalamus.
AB  - The functional parcellation of the motor thalamus of primates has suffered from
      serious historical and technical drawbacks, which have led to extreme confusion.
      This is a problem when thalamic stereotaxy is again being use clinically. The
      cause usually imputed is the historical conflict between two main schools, the
      Vogt and the 'Anglo-American' (Michigan), which used different nomenclatures. In
      fact, the reasons are more profound and serious. A combination of them led to: an
      archaic, rigid conception of the 'thalamic nucleus'; overexploitation of
      cytoarchitectonic technique, comparative anatomy and cortical connections;
      underexploitation of subcortical afferent territories; recent misuse of these
      territories; hesitations in the use of the VA-VL system; and opposition between
      ventral ('relay') and dorsal ('associative') 'nuclei'. Previous and current
      parcellations and nomenclatures for the lateral region finally appeared
      inappropriate. Before presenting a new parcellation and nomenclature for the
      lateral region, we explain why we did not adopt one of most common or of recently
      proposed nomenclatures, and were led to make our own. This is established
      according to rational and historically grounded rules. Precise definition of
      thalamic elements is provided. A thalamic 'region' is a gross topographic
      division corresponding to the former nuclei. A 'territory' is defined as the
      cerebral space filled by afferent endings from one source. When having a distinct
      topography in a region, a given territory makes a 'subregion'. For each of the
      studied 'motor' territories a review was made of its known cortical projections.
      The thalamic space where neurons project to a given cortical target constitutes a
      'source space'. Topographical comparison of the sources spaces with territories
      reveals that there is often no coincidence between different (afferent or
      efferent) neuronal set spaces. It appears that source spaces are coincident in
      the pallidal and nigral territories but not in the cerebellar territory where two
      topographically distinct source spaces could be distinguished. A 'thalamic
      nucleus' is defined as the intersection of a thalamocortical source space with
      one territory. A rapid review of the general anatomy of the diencephalon is made.
      The ('dorsal') thalamus is divided into 'allo-' and 'isothalamus', the latter
      with 'bushy' and 'microneurons'. The lateral region is isothalamic. The 'motor
      thalamus' makes the anterior part of the lateral region. The present work aims to
      analyse the functional anatomy of the 'motor thalamus' by using precise
      topography and three-dimensional analyses of the subcortical territories
      receiving from the cerebellar nuclei (part II), the medial nucleus of the
      pallidum (part III) and the pars reticulata and mixta of the substantia nigra
      (part IV). Large injections were used to obtain the maximal extent of each
      territory. A major deficiency of previous studies was inadequate catography.
      Reliance on ventricular (CA-CP) landmarks observed by use of orthogonal
      teleradiography is mandatory. A study was made of intra- and interspecific
      variations and their effect on stereotactic and cartographic precision in
      macaques. All three subcortical motor afferent territories to the motor thalamus
      of macaques are examined in precise cartography with three dimensional
      reconstructions, rotations and 'reslicing'. The motor thalamus is made up of
      three topographically distinct and separate territories: cerebellar, pallidal
      territory and nigral. They cover the entire anterior part of the lateral region.
      There is no polar subdivision without lower afferents in front of the pallidal
      and nigral territories and thus no reason for isolating a nucleus lateralis
      polaris or a polar VA. The cerebellar territory is continuous and dense, in front
      of the somesthetic nucleus and everywhere separate from it. It has a complex
      three-dimensional shape, strongly convex anteriorly. Its caudal portion is dorsal
      to the somesthetic nucleus.(ABSTRACT

PMID- 8883917
TI  - The role of cerebral noradrenergic systems in the Fos response to interleukin-1.
AB  - Peripheral administration of interleukin-1 (IL-1) has been shown to activate
      induction of Fos in the brain, but the mechanism is not known. Because cerebral
      noradrenergic systems have been implicated in Fos induction, we studied the IL-1
      induced appearance of Fos in mice pretreated with 6-hydroxydopamine (6-OHDA)
      which depleted cerebral norepinephrine (NE) by more than 90%, but did not
      significantly alter dopamine. Intraperitoneally injected IL-1 beta increased Fos
      in several brain regions, but most obviously in the hypothalamic paraventricular
      nucleus (PVN). Pretreatment with 6-OHDA substantially reduced the IL-1-induced
      Fos increase in the PVN which was no longer statistically significant. When the 6
      OHDA treatment was preceded by administration of desmethylimipramine which
      prevents NE depletion, IL-1 treatment increased Fos in the PVN, suggesting that
      the effect of 6-OHDA was indeed related to the depletion of NE. These results
      suggest that the noradrenergic innervation of the PVN is involved in the IL-1
      induced induction of Fos in the PVN. By contrast with previous experiments is
      rats, the IL-1-induced increase in plasma corticosterone was not significantly
      altered by the 6-OHDA pretreatment in mice.

PMID- 8883919
TI  - Inositol monophosphatase, the putative therapeutic target for lithium.
AB  - Lithium has been hypothesised to exert its therapeutic effects in the treatment
      of bipolar disorder by attenuating phosphatidylinositol (PI) cell signalling
      pathways that are presumably hyperactive in this disorder. More specifically,
      lithium has been proposed to inhibit inositol monophosphatase (IMPase) thereby
      causing a depletion of intracellular inositol which results in a reduction in the
      synthesis of the PI required to sustain this signalling pathway. In the present
      article this 'inositol depletion' hypothesis will be reviewed and pathological,
      pharmacodynamic, developmental and anatomical aspects of IMPase as well as
      inhibitors of this enzyme will be described.

PMID- 8883920
TI  - Brain events related to normal and moderately scrambled faces.
AB  - The neural basis of normal and scrambled face processing was investigated by
      recording evoked potentials from 21 electrodes at standard EEG sites, with
      respect to a nose reference. Temporal negativities were found that result from
      two overlapping phenomena: they arise from the polarity reversal on temporal
      electrodes of the vertex P2, a positive wave peaking about 170-200 ms after the
      onset of a face stimulus, and also from an overlapping 'processing negativity' of
      long duration associated with the processing difficulty of the scrambled face
      stimulus. The comparisons of scalp potential and current density mappings support
      the proposal that some neuronal networks are active both for faces and scrambled
      faces and are compatible with the involvement of the superior temporal sulcus,
      the inferotemporal cortex and the parahippocampal and fusiform gyri, whereas the
      processing negativity would only involve the deepest generators of this network.
      Furthermore, the encoding of both faces and scrambled faces seems to take place
      predominantly in the right hemisphere.

PMID- 8883921
TI  - Event-related potentials during auditory and somatosensory discrimination in
      sighted and blind human subjects.
AB  - The objective of the present study was to test if and to what extent phasic and
      tonic event-related potentials of the human EEG may reflect phenomena of cortical
      plasticity. In particular, it was tested if the occipital cortex of blind
      subjects participates in the processing of non-visual stimuli. To this end, 12
      blind and 12 blindfolded sighted subjects were tested in an auditory and a
      somatosensory discrimination task with 2 levels of discrimination difficulty.
      Slow and fast event-related potentials were recorded from 18 scalp electrodes. In
      addition to the negative slow waves found in sighted subjects over frontal and
      central sites during auditory and somatosensory discrimination, a pronounced
      negative wave was revealed in the blind also over occipital brain areas. These
      negative shifts were time-locked to the train of stimuli which had to be
      monitored with sustained attention, i.e. they rised and resolved with the
      beginning and the end of a 20-s discrimination time epoch. The P300 complex, on
      the other hand, which is a slow positive deflection over the posterior part of
      the scalp and which follows rare and task-relevant events 200-800 ms after
      stimulus onset was significantly smaller at occipital electrodes in the blind
      than in the sighted subjects. Combined with neurophysiological and
      neuronanatomical evidence originating from studies with visually deprived
      animals, these data suggest that the occipital cortex of blind human subjects is
      coactivated whenever the system is engaged in a task which requires sustained
      attention and is less effectively inhibited at the end of a perceptual time
      epoch. In total, the data cast doubt on the hypothesis that the occipital cortex
      of blind subjects participates in modality-specific non-visual information
      processing.

PMID- 8883922
TI  - Reappearance of event-related P3 potential in locked-in syndrome.
AB  - In a patient affected by locked-in syndrome, because of a lesion of the caudal
      ventral pontine tegment, we recorded event-related potentials (ERPs) to an
      acoustic odd-ball paradigm. We did not record N2 and P3 components in the 50 days
      following the acute lesion although the patient was able to understand the task
      and communicate with blinking. 55 days after the acute lesion, N2 and P3
      reappeared on scalp derivations. This findings suggest that brainstem structures
      are involved in P3 or N2-P3 generation.

PMID- 8883923
TI  - Dissimilar age influences on two ERP waveforms (LPC and N400) reflecting semantic
      context effect.
AB  - Age-related changes in semantic context effects were examined using late event
      related brain potentials (ERPs). Auditory ERPs to semantically congruous and
      incongruous final words in spoken sentences were recorded in 16 children (aged 5
      11 years) and 16 adults. Previous findings concerning age-related effects on N400
      were replicated: the N400 effect was significantly larger in children than in
      adults. The main new finding was that a late positive component (LPC) following
      N400 and modulated by semantic context in adults was not found in children. Thus,
      the common generalization that semantic context effects decline with age holds
      only for ERP components occurring in the N400 time window or earlier. The
      cognitive function reflected by the semantic LPC we observed is not clear, but it
      seems to have a role different from that of the N400, although in adults the
      components often co-exist as an N400-LPC complex.

PMID- 8883924
TI  - Administration of lanthanum chloride following a reminder induces a transient
      loss of memory retrieval in day-old chicks.
AB  - Lanthanum chloride (5.0 mM) administered immediately after a visual reminder
      presented to day-old chickens between 7.5 min and 48 h following a single trial
      passive avoidance learning task produced an immediate but transient loss of
      memory on retention test, an effect not observed in the absence of a reminder.
      The duration of the transient deficit was relatively stable with lanthanum
      chloride consistently inducing a loss of memory that was evident 5 min after the
      reminder, with recovery by 10-15 min. The results suggest that, for a period of
      at least up to 48 h after passive avoidance training, the activation of memory
      retrieval by a reminder stimulus may lead to processes which are sensitive to
      inhibition by the calcium channel antagonist lanthanum chloride. These results
      extend previously reported findings implicating the involvement of glutamate
      sensitive channels in a transient memory process that is also activated as a
      result of a reminder stimulus, but that is no longer present 48 h after training.
      The glutamate-sensitive mechanism appears to be a secondary mechanism activated
      following memory retrieval and to be dependent on the level of memory
      consolidation that the memory for the original experience has undergone. The
      results presented here suggest that lanthanum chloride, a calcium channel
      antagonist, inhibits memory retrieval in the day-old chick. This effect
      implicates calcium channel mediated processes in immediate memory recall.
      Further, the results suggest the lanthanum inhibits a primary mechanism, that
      precedes that glutamate-sensitive mechanism identified previously and that both
      are dependent on the activation of memory retrieval by a reminder.

PMID- 8883926
TI  - N400-like potentials elicited by faces and knowledge inhibition.
AB  - Within the theoretical framework of reference, the brain errs in processing
      complex stimuli, such as faces. Thus, these stimuli not only activate accurate
      representations but also inaccurate representations corresponding to known
      persons who resemble the face stimulus, and hence knowledge about these known
      persons. Since more errors are made in processing unfamiliar than familiar
      stimuli, these inaccurate activations are assumed to be more frequent, and/or
      more intense, with unknown than with known faces. Moreover, top-down mechanisms
      favor representations of stimuli that are congruent with the context, and
      representations of known persons, even if inaccurate, receive an additional
      amount of activation in contexts wherein known faces are expected. Inaccurate
      representations have to be inhibited to achieve accurate recognition. Thus, more
      inhibition would be required for unknown than for known faces, and in contexts
      wherein known faces are expected. The aim of the present work is to study the
      hypothesis that the N400 component of the event-related potentials (ERPs)
      reflects the inhibition of knowledge, and to see whether this hypothesis accounts
      for the N400-like potential elicited by faces. To achieve that goal, ERPs to
      known and unknown faces were recorded while the richness in known faces of each
      experimental block, and thus the expectancy for known faces, was manipulated.
      Consistent with the hypothesis, the amplitudes of the N400-like components were
      greater in conditions where more inhibition was required, i.e. for unknown rather
      than for known faces, and in the context of the block rich in known faces. This
      context effect was larger for unknown than for faces, and in the context of the
      block rich in known faces. This context effect was larger for unknown than for
      known faces.

PMID- 8883925
TI  - Oscillatory neuromagnetic activity induced by language and non-language stimuli.
AB  - Event-related oscillatory brain activity during language perception differs from
      activity occurring during the processing of comparable non-language stimuli. This
      fact became apparent in the observation of changes in the normalized spectral
      power of magnetoencephalographic (MEG) signals during the subject's processing of
      these stimuli. MEG was recorded over the left and right hemispheres of 12 right
      handed subjects. During the experimental session, bisyllablic content words and
      physically similar non-language stimuli were presented with equal probability in
      a randomized order in either the visual or auditory modality. Approximately 15%
      of these stimuli were marked and the subject's task was to detect these marked
      stimuli. As a major characteristic of language vs. non-language processing, we
      obtained an enhancement of the normalized spectral power around 240 ins in the 60
      65-Hz band over the left hemisphere for the language condition and over the right
      hemisphere for the non-language condition, independent of the modality of
      stimulus presentation. Starting at approximately the same latency but in lower
      frequency bands (15-45-Hz), an extended (250-600 ms) reduction of normalized
      spectral power was observed. This reduction, although it generally confirmed
      previous results, differed in the no hemisphere-specific reduction was found for
      the processing of words. A domain-specific enhancement of normalized spectral
      power was also evident around 800-1200 ms in the 15-30-Hz band. In the auditory
      condition, this enhancement of the normalized spectral power was larger after the
      presentation of language stimuli whereas in the visual condition a larger
      enhancement of the normalized spectral power was obtained after presentation of
      non-language stimuli. As this latter effect appears relatively late after the
      stimulus onset and differs in expression for both modalities of stimulus
      presentation, a simple relationship between language perception and oscillatory
      brain dynamics can be excluded for this enhancement. In contrast, the left
      hemispheric enhancement of the normalized spectral power present around 240 ms in
      the 60-65-Hz band seems to reflect oscillatory pattern specific to the processing
      of words.

PMID- 8883927
TI  - Preattentive periodicity detection in auditory patterns as governed by time and
      intensity information.
AB  - The present study demonstrated that the mismatch negativity (MMN), generated by
      the brain's preattentive detection of a sound change, is elicited by infrequent
      reversals of two consecutive tones differing in intensity. When tones were
      presented in a pairwise manner, the MMN was time-locked to the onset of the
      intensity reversal. When the tones were continuously presented, the MMN was
      elicited by an irregular loud tone succeeding a regular loud tone but not by an
      irregular soft tone following a regular soft tone. Results suggest that the
      preattentive construction of auditory units is primarily governed by the timing
      of tone presentation but that it may also utilize intensity information, when no
      sufficient timing information is available.

PMID- 8883928
TI  - Expression of serotonin receptors in human fetal astrocytes and glioma cell
      lines: a possible role in glioma cell proliferation and migration.
AB  - Expression of seven serotonin or 5-hydroxytryptamine (5-HT) receptors (5-HT1D
      alpha, 5-HT1E, 5-HT2, 5-HT1A, 5-HT1C, 5-HT1D beta, and 5-HT6) was investigated in
      human normal fetal astrocytes and eight glioma cell lines by reverse
      transcription and polymerase chain reaction (RT-PCR). No expression of 5-HT1D
      beta and 5-HT6 was observed in any of the cell lines studied. The 5-HT1D alpha
      receptor was found to be expressed in two human glioma cell lines but not in
      normal astrocytes. In addition, only three glioma cell lines expressed the 5-HT1E
      receptor. The 5-HT1C receptor was expressed in six glioma cell lines but not in
      normal astrocytes while the 5-HT1A was found to be expressed in normal astrocytes
      from the left hemisphere and in six glioma cell lines but not in normal
      astrocytes from the cerebellum. Interestingly, the 5-HT2 receptor was expressed
      in all cells studied but very weakly in normal astrocytes. The effect of 5-HT on
      glioma cell proliferation, migration, and invasion was also investigated.
      Serotonin was found to positively modulate these three processes in vitro. These
      results suggest that 5-HT may play an important role in the control of the
      biological properties of human glioma cells.

PMID- 8883929
TI  - Regulation of androgen receptor mRNA expression in hamster facial motoneurons:
      differential effects of non-aromatizable and aromatizable androgens.
AB  - We have previously shown inherent sex differences in the levels of androgen
      receptor mRNA (AR mRNA) in hamster facial motor neurons (FMN). FMN of intact
      females contained approximately 50% less AR mRNA than their male counterparts.
      Gonadectomy in males down-regulated AR mRNA levels in FMN by approximately 50%,
      whereas no effects of gonadectomy were observed in females. Sex differences in
      the regulation of AR mRNA levels by exogenous testosterone propionate (TP) were
      also observed. In those studies, AR mRNA levels were up-regulated after 1 day of
      treatment with exogenous TP in FMN of gonadectomized (GDX) males and after 7 days
      in FMN of intact females, with no effects in GDX females. Since TP is
      aromatizable to estrogen, and given recent findings of transient expression of
      estrogen receptors (ER) in rodent FMN, the effects of dihydrotestosterone (DHT),
      a non-aromatizable form of the steroid, on AR mRNA expression in hamster FMN were
      examined in the present study. If testosterone (TES) were the active hormone
      regulating AR mRNA levels in FMN, DHT treatment should render a similar
      regulatory pattern as TP, but if metabolism of TES to estradiol plays a role in
      AR mRNA regulation, effects of the two treatments should differ. In situ
      hybridization and computerized image analysis were used to quantify the
      regulation of AR mRNA by DHT in individual FMN of hamsters of both sexes.
      Exogenous DHT was administered to intact and gonadectomized (GDX) male and female
      hamsters by implantation of one 10-mm Silastic capsule for 1, 2 or 7 days. AR
      mRNA levels were significantly up-regulated in intact females at all time points
      of DHT exposure, with no effects in GDX groups. These results differ from
      previous work using TP, in which a modest up-regulation in AR mRNA levels was
      observed in FMN of intact females only after 7 days. As with TP, DHT exposure
      gradually down-regulated AR mRNA levels in FMN of intact males. Thus, DHT only
      regulated AR mRNA levels in intact animals, with endogenous sources of estrogen
      available, but not in GDX animals, with endogenous estrogens reduced by
      gonadectomy. Taken together, these results substantiate our previous findings of
      sex differences in AR mRNA levels/regulation and suggest a synergism between
      estrogen and androgen in the regulation of AR mRNA levels in peripheral motor
      neurons.

PMID- 8883930
TI  - The mesolimbic dopaminergic pathway is more resistant than the nigrostriatal
      dopaminergic pathway to MPTP and MPP+ toxicity: role of BDNF gene expression.
AB  - In the present study we examined the role of BDNF gene expression involved in the
      differential vulnerability of the nigrostriatal and mesolimbic dopaminergic
      pathways to environmental damage. The toxins for dopamine (DA) neurons 1-methyl-4
      phenyl-1,2,3,6,-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+)
      were used as pharmacological tools. Results revealed that chronic MPTP treatment
      produced a significant and irreversible DA depletion in the striatum (ST) as well
      as a marked decrease in tyrosine-hydroxylase (TH) mRNA level in the substantia
      nigra (SN). Under these conditions, the endogenous brain-derived neurotrophic
      factor (BDNF) mRNA level was increased in the SN. Only acute DA reduction was
      found in the nucleus accumbens (NAc) and TH mRNA level was not affected in the
      ventral tegmental area (VTA) by MPTP treatment. Further, when MPP+ produced a
      similar extent of DA depletion in the ST and NAc, the TH mRNA level was also
      decreased while BDNF mRNA level was increased in the SN. The same alterations
      were not observed in the VTA. Results from the BDNF mRNA regional distribution
      study revealed that structures in the mesolimbic dopaminergic pathway expressed a
      more than 2-fold higher basal BDNF mRNA level than structures in the
      nigrostriatal dopaminergic pathway. Presumably, enhanced BDNF gene expression
      would help the survival of DA neurons and these findings suggest a better
      protective mechanism in the mesolimbic pathway. Lastly, direct BDNF infusions to
      the SN partially protected against MPTP's toxicity on DA neurons in the ST in
      mice. These results together suggest that a more abundant BDNF mRNA level along
      the mesolimbic pathway than the nigrostriatal pathway may, at least partially,
      explain the differential vulnerability of different DA neurons to MPTP and MPP+
      toxicity.

PMID- 8883931
TI  - Involvement of the caudal striatum in auditory processing: c-fos response to
      cortical application of picrotoxin and to auditory stimulation.
AB  - The topographical organization of corticostriatal connections have been
      postulated to follow a longitudinal pattern, each cortical area projecting on a
      longitudinal strip stretching along the whole rostro-caudal axis of the striatum.
      However, compared to the rostral striatal region, the caudal striatum exhibits
      distinct features in terms of connectivity and neuronal phenotype. The induction
      of c-fos expression in the striatum by cortical activation or sensory stimulation
      may throw more light on these functional corticostriatal relationships. In the
      present study, we examined the effects of cortical activation by local
      application of picrotoxin on the Fos-immunoreactivity (Fos-IR) in the striatum of
      the mouse, with special reference to the caudal part of the striatum. Activation
      of the auditory cortex induced a dense ipsilateral Fos-IR restricted to the
      caudal striatum i.e., in the caudo-medial striatum and in the caudal part of
      fundus striati, and a very sparse labelling in the medial region of the rostral
      striatum. Conversely, activation of both sensori-motor and visual cortices only
      resulted in Fos-IR in the main rostral part of the striatum, without response in
      the caudal extremity of the striatum. On the other hand, visual or auditory
      stimulation in awake animals failed to induce c-fos expression in the striatum.
      However, using quantitative in-situ hybridization for c-fos mRNA, we found that
      auditory, but not visual stimulation significantly potentiated the c-fos response
      to the D1 agonist SKF 38393 (2 mg/kg, i.p.) in the caudal part of the striatum.
      These functional observations suggest that, despite a more widespread cortico
      striatal connection pattern deduced from tracing experiments, the strongest
      functional projections from the auditory system mainly converge onto a restricted
      part of the caudal striatum, according to a connection pattern that is
      reminiscent of the transverse segmentation proposed in early lesioning studies of
      corticostriatal projections.

PMID- 8883932
TI  - Neuronal nitric oxide synthase (nNOS) mRNA expression and NADPH-diaphorase
      staining in the frontal cortex, visual cortex and hippocampus of control and
      Alzheimer's disease brains.
AB  - Neuronal nitric oxide synthase (nNOS) mRNA levels and NADPH diaphorase (NADPH-d)
      staining were compared in the frontal cortex, visual cortex and hippocampus
      (dentate gyrus and CA subfields of Ammon's horn) of five Alzheimer's disease (AD)
      and six control brains. The cellular abundance of nNOS mRNA was quantified by in
      situ hybridisation using 35S-labelled antisense oligonucleotides complementary to
      the human nNOS sequence. Although the mean level of nNOS expression was decreased
      in all three regions in AD cases as compared to controls, it did not reach
      significance. Neurones positively labelled for nNOS mRNA and neurones positive
      for NADPH-d histochemistry displayed similar distribution in control and AD
      cases. In AD brains the density of neurones having detectable levels of nNOS mRNA
      was significantly decreased in the white matter underlying the frontal cortex (P
      < 0.05) but not in the frontal cortex gray matter; no change was observed in the
      gray or white matter of the visual cortex in AD. The number of cells expressing
      detectable levels of nNOS mRNA in the hippocampus was also significantly
      decreased (P < 0.05) in AD. The density of NADPH-d-positive cells was not
      significantly decreased in the gray or white matter of the frontal or visual
      cortices in AD compared to controls; however, the number of NADPH-d-positive
      cells was significantly decreased in the hippocampus (P < 0.01). These data
      indicate that although the cellular abundance of nNOS mRNA is not significantly
      decreased in these three regions in AD, there is a significant decrease in the
      number of cells expressing detectable levels of nNOS mRNA in the white matter
      underlying the frontal cortex and in the dentate gyrus and CA subfields of the
      hippocampus in AD. Furthermore, there was also a significant decrease in the
      number of NADPH-d-positive cells in the dentate gyrus and CA subfields of the
      hippocampus in AD as compared to controls. These results suggest specific
      populations of nNOS/NADPH-d cells in the white matter underlying the frontal
      cortex and in the hippocampus are vulnerable in AD. The implications of these
      findings are discussed.

PMID- 8883933
TI  - Creatine kinase-B mRNA levels in brain regions from male and female rats.
AB  - The creatine kinase-B (CKB) enzyme is proposed to have a pivotal role in the
      regeneration of ATP in the nervous system. In the present study, the steady-state
      levels of CKB mRNA were determined by RNase protection assay in seventeen
      separate brain regions obtained from rats during the initial interval of the
      light period or period of inactivity in rats. The antisense probe used
      specifically hybridizes to CKB mRNA and discriminates CKB from CKM mRNA. The
      results show that brain regions from Wistar rats differ in CKB mRNA content.
      Highest levels of CKB mRNA were detected in the male and female cerebellum. High
      levels of CKB mRNA were observed in the spinal cord, brain stem and its
      structures (medulla, pons and midbrain) and olfactory bulb of the male rats.
      Female rats also contained high levels of CKB mRNA in the brain stem. In both
      male and female rats, the frontal cortex, occipital cortex, hippocampus and
      striatum exhibited lower levels of CKB mRNA relative to the complete brain.
      Statistical analyses demonstrated a significant difference between the male and
      female CKB mRNA profiles. However, CKB mRNA levels in brain regions with estrogen
      receptors (hypothalamus, hippocampus) were similar in male and female rats.
      Differential CKB mRNA levels in various brain regions may suggest diverse
      physiological significance of the CKB system in the regulation of brain energy
      metabolism.

PMID- 8883934
TI  - Changes in the expression of transcription factors ATF-2 and Fra-2 after axotomy
      and during regeneration in rat retinal ganglion cells.
AB  - The expression of one member of the bZip superfamily of transcription factors, c
      Jun, is known to be induced by axotomy in retinal ganglion cells (RGCs) and is
      associated with axonal regrowth. This study used immunohistochemistry combined
      with retrograde labeling to examine the expression of two additional bZip
      transcription factors (ATF-2 and Fra-2) in identified adult rat RGCs under
      favorable and unfavorable conditions for axonal regrowth. For unfavorable
      regrowth conditions, ganlgion cell axons within the optic nerve were cut close to
      the eye. For favorable conditions, the optic nerve was replaced with an
      autologous peripheral nerve graft to allow axonal regrowth. At regular intervals,
      after axotomy alone or in conjunction with graft placement, the expression of
      these transcription factors was examined in retinal wholemounts using protein
      specific antibodies. The strong cytoplasmic expression of Fra-2 seen in
      unaxotomized RGCs was reduced beginning 24 h after axotomy. Similarly, the strong
      nuclear expression of ATF-2 seen prior to axotomy was also reduced after axotomy.
      These reduction persisted in surviving ganglion cells throughout the 3 week study
      period. One to 6 months after axotomy and peripheral nerve graft placement,
      identified RGCs with regrown axons showed strong ATF-2 and Fra-2 expression,
      suggesting a return to basal conditions. These findings support roles for ATF-2
      and Fra-2 in the survival and regeneration process of these central nervous
      system neurons after axotomy.

PMID- 8883936
TI  - Transient expression of the mitogen-activated protein kinase phosphatase MKP-1
      (3CH134/ERP1) in the rat brain after limbic epilepsy.
AB  - The immediate early gene-encoded enzyme, MAP kinase phosphatase 1 (MKP-1), is
      thought to be a key element in controlling cellular signalling pathways activated
      by MAP kinases. Since MAP kinase have been demonstrated to participate in
      neuronal stimulus-transcription coupling following seizure activity, the present
      study investigated the induction of MKP-1 in the rat brain after limbic epilepsy.
      MKP-1 expression was studied with a polyclonal antiserum by Western blots,
      immunocytochemistry and immuno-electron microscopy at different time periods
      between 1 and 24 h after kainic acid-induced limbic seizures. MKP-1 induction was
      identified in dentate granule cells of the hippocampus but not in pyramidal
      neurons, furthermore in neurons of the outer layers of the neocortex, as well as
      in neurons of the lateral nucleus of the bed of the stria terminalis. Immuno
      electron microscopy demonstrated that MKP-1 was localized in the neuronal
      nucleus, where the substrate of MKP-1, activated MAP kinases, are also found. In
      view of the restricted areas of MKP-1 expression and the widespread areas of
      altered MAP kinases activity it can be concluded that in the majority of CNS
      populations other mechanisms than MKP-1 induction are responsible for the shut
      off of MAP kinases following seizure activity. MKP-1 may contribute in the
      specific subpopulations where it is induced to the post-translational control of
      inducible transcription factors of the fos, jun and myc family.

PMID- 8883935
TI  - Cultured astrocytes express biglycan, a chondroitin/dermatan sulfate proteoglycan
      supporting the survival of neocortical neurons.
AB  - Astrocyte-conditioned medium (ACM) supports the survival of rat E15 neocortical
      neurons. Using a microtiter assay for neuronal survival, we demonstrated that
      part of the survival activity is associated with a proteoglycan fraction obtained
      after two chromatographic steps: (1) preparative Q-Sepharose anion-exchange
      chromatography under non-denaturating conditions and (2) MonoQ chromatography in
      the presence of 8 M urea. Analytical SDS-polyacrylamide gradient gel
      electrophoresis of pooled active MonoQ-fractions (MQ-pool) revealed a broad
      proteoglycan band migrating with an apparent M(r) in the range of 150-400 kDa.
      Digestion of the MQ-pool with chondroitin-ABC-lyase yielded a major core protein
      of 50 kDa. In Western blots the high molecular weight (150-400 kDa) material as
      well as the 50 kDa core protein band were immunoreactive to chicken polyclonal
      antibodies raised against purified biglycan from rat meningeal fibroblasts.
      Northern blot analysis of total RNA prepared from highly enriched astrocyte
      cultures revealed a single 2.9 kb biglycan transcript. By using in situ
      hybridization we demonstrated that essentially all cells in these cultures
      expressed biglycan mRNA. Furthermore, highly purified biglycan from bovine
      cartilage was shown to markedly enhance survival of rat neocortical neurons. In
      conclusion, we have shown that astrocytes synthesize and release the small
      chondroitin/dermatan sulfate proteoglycan (CS/DSPG) biglycan, a molecule that was
      found to support survival of neocortical neurons in vitro.

PMID- 8883938
TI  - Expression of c-fos, jun D and pp60c-src+ mRNAs in the developing and grafted rat
      striatum.
AB  - Expression of the mRNAs of the proto-oncogenes pp60c-src+, c-fos and jun D were
      studied using in-situ hybridisation histochemistry in the developing striatum and
      in striatal grafts. The temporal patterns of mRNA expression were monitored in
      the striatum of the normal developing rat from the 12th day of gestation (E12) to
      10 days postnatally, and were compared to the changes in gene expression observed
      in E13-E14 primordial striatal tissue grafts 7, 15 and 30 days after implantation
      in the ibotenic acid-lesioned striatum of adult rats. During development, all
      three proto-oncogenes were most highly expressed just before birth, at E19.
      Striatal expression of all three proto-oncogenes was markedly reduced after birth
      and remained at a low level through to adulthood. A different mode of expression
      was observed in the transplanted striatum which was unique to each particular
      gene. jun D and pp60c-src+ were expressed for a longer time period in the grafted
      primordial cells than in normal development, whereas no c-fos expression could be
      detected in the grafts. These results suggest that transplantation of embryonic
      neural cells into the host brain may affect the normal developmental regulation
      of such cells and their expression of some proto-oncogenes.

PMID- 8883937
TI  - Molecular cloning of ictacalcin: a novel calcium-binding protein from the channel
      catfish, Ictalurus punctatus.
AB  - Calcium is essential for a variety of functions in animals, including signal
      transduction, transmission of nerve impulses, and bone and scale growth. In
      freshwater adapted teleosts, blood calcium levels are maintained constant (2-4
      mM) even at low external calcium concentration (< 0.01 mM). Epithelial cells in
      skin and gill have been implicated in calcium homeostasis. We have cloned a cDNA
      from Ictalurus punctatus, the channel catfish, that codes for ictacalcin, a novel
      member of the S100 family of calcium-binding protein. In-situ hybridization
      demonstrates ictacalcin mRNA is abundant in epithelial cells of olfactory
      rosette, barbel, skin and gill but not brain or muscle. The presence of
      ictacalcin protein in these tissues was confirmed by immuno-blot analysis. Tissue
      extracts and recombinant ictacalcin bind calcium with attendant changes in
      electrophoretic mobility indicative of changes in protein conformation. The
      calcium-binding activity and abundant localization of ictacalcin in epithelial
      cells of several tissues indicates that this protein plays an important role in
      catfish calcium homeostasis.

PMID- 8883939
TI  - Regulation of alternative splicing of NMDAR1 in the kindling model.
AB  - Kindling refers to a phenomenon in which repeated application of initially
      subconvulsive electrical stimulations produces limbic and clonic motor seizures
      of progressively increasing severity. Once established, the increased
      excitability is lifelong. Several lines of investigation suggest that the N
      methyl-D-aspartate (NMDA) subtype of glutamate receptor participates in the
      expression of the increased neuronal excitability of the kindled brain. Many
      studies demonstrate that kindling results in altered NMDA receptor functional and
      pharmacological properties, indicating that kindling may cause changes intrinsic
      to the NMDA receptor itself. It is possible that altered expression of NMDA
      receptor subunit genes and splice isoforms of genes leads to subunit combinations
      resulting in the novel NMDA receptor properties identified in the hippocampus of
      kindled animals. To begin to address this possibility, we previously examined the
      hippocampal expression of known NMDA receptor genes and found no differences in
      expression between control and kindled animals either 24 h or 28 days after the
      last kindled seizure. Here, we extend that earlier study by examining the
      expression of NMDAR1 splice isoforms in the hippocampus of control and kindled
      animals. We report that kindling induces the transient reduction of specific
      splice isoforms of NMDAR1 containing the first of the carboxy-terminal splice
      cassettes (exon 21). We discuss the potential significance of this regulation in
      terms of its relevance to previous findings in the kindling model and possible
      effects on NMDA receptor function.

PMID- 8883940
TI  - Tetrahydrobiopterin biosynthesis in C6 glioma cells: induction of GTP
      cyclohydrolase I gene expression by lipopolysaccharide and cytokine treatment.
AB  - The possibility that 5,6,7,8-tetrahydrobiopterin (BH4) biosynthesis is stimulated
      in glial cells by treatment with lipopolysaccharide (LPS) and tumor necrosis
      factor (TNF-alpha) was examined in the astrocyte-derived C6 glioma cell line.
      Under basal culture conditions BH4 levels were found to be at the limit of
      detection. Concurrent treatment with 10 micrograms/ml LPS and 50 ng/ml TNF-alpha
      caused a time-dependent 13-fold increase in the levels of BH4. This treatment
      paradigm also induced nitric oxide synthase activity, as evidenced by increased
      levels of nitrite, an oxidized metabolite of NO, in the culture medium. LPS and
      TNF-alpha treatment led to a 25-fold increase in GTPCH enzyme activity, the first
      and rate-limiting enzyme in BH4 synthesis, and a corresponding 23-fold increase
      in GTPCH protein levels. Northern blot analysis showed that increased levels of
      GTPCH mRNA preceded changes in GTPCH protein, GTPCH enzyme activity and BH4
      levels and reached a maximal of 44-fold that was sustained for at least 48 h.
      These results demonstrate that LPS and TNF-alpha stimulate de-novo BH4
      biosynthesis and suggest that C6 cells offer a model system for studying the
      molecular events that control the induction of GTPCH gene expression and BH4
      synthesis in glial cells.

PMID- 8883941
TI  - Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B
      suggests a gene regulatory role in several brain regions including the
      nigrostriatal dopamine system.
AB  - Nurr1 and NGFI-B are closely related orphan members of the steroid-thyroid
      hormone receptor family involved in immediate early responses to stimuli such as
      growth factors. In-situ hybridization in the developing and adult mouse and rat
      demonstrated Nurr1 mRNA in several regions during early central nervous system
      (CNS) development. Expression persisted through the pre- and postnatal periods
      and was also found in several areas in the adult CNS. Positive areas include the
      olfactory bulb, parts of the cortex, the hippocampal formation and substantia
      nigra where Nurr1 and tyrosine hydroxylase mRNAs were co-expressed. 6
      Hydroxydopamine-induced degeneration of mesencephalic dopamine neurons led to a
      corresponding loss of Nurr1 mRNA, demonstrating a link between Nurr1 and
      dopaminergic neurons. NGFI-B mRNA was not found in the prenatal CNS but was
      highly expressed in the adult brain in many areas including the olfactory bulb,
      cortex, basal ganglia and hippocampus. The spatiotemporal distribution of Nurr1
      and NGFI-B mRNAs suggests that these transcription factors are involved in the
      development and maturation of specific sets of CNS neurons. The experimental data
      imply that one of these functions may be to control gene regulatory events
      important for development and function of those neurons that degenerate in
      patients with Parkinson's disease.

PMID- 8883942
TI  - Effects of dexfenfluramine or 5,7-dihydroxytryptamine on tryptophan hydroxylase
      and serotonin transporter mRNAS in rat dorsal raphe.
AB  - Dexfenfluramine (DF), given in high doses, can produce long-lasting decreases in
      brain levels of serotonin (5-HT) and 5-HT transporter (5-HTT) protein. The
      purpose of this study was to determine if DF-induced decreases in 5-HT and 5-HTT
      in rat forebrain are correlated with compensatory changes in the expression of
      the genes for tryptophan hydroxylase (TPH) and 5-HTT in the dorsal raphe nucleus.
      Gene transcripts were measured by quantitative reverse transcription-polymerase
      chain reaction (RT-PCR). Rats were treated with either one or eight injections of
      DF at either high (10 mg/kg) or low (2 mg/kg) doses. A positive control group for
      5-HT cell loss received a single cerebroventricular injection of 5,7
      dihydroxytryptamine (DHT). Rats were killed either 5, 15 or 30 days after their
      last treatment. Paroxetine binding to the 5-HTT protein in frontal cortex was, as
      expected, reduced in all of the treated groups relative to vehicle controls. TPH
      mRNA levels in the dorsal raphe of animals that received DHT were significantly
      higher than those measured in all other treatment groups 15 days following
      treatment. By 30 days, the amount of TPH mRNA in DHT-treated rats had fallen to
      well below control levels. None of the DF regimens significantly affected TPH
      mRNA levels. Unlike the TPH mRNA changes in DHT-treated rats, the 5-HTT mRNA
      levels in the dorsal raphe declined progressively throughout the 30 day survival
      period. None of the DF regimens significantly affected 5-HTT mRNA levels. The
      significance of these data are discussed in terms of whether loss of forebrain
      markers for 5-HT reflects either the loss of fine caliber 5-HT axon terminals or
      a decrease in the expression of these markers in the somata of these cells which
      are located in the dorsal raphe.

PMID- 8883943
TI  - Distribution and levels of insulin-like growth factor (IGF-I and IGF-II) and
      insulin receptor binding sites in the spinal cords of amyotrophic lateral
      sclerosis (ALS) patients.
AB  - The structurally related peptides, insulin and insulin-like growth factors (IGF-I
      and IGF-II), have neurotrophic properties and potentially could be of therapeutic
      value in human neurodegenerative disorders. In this study, we compared the
      anatomical distribution of [125I]IGF-I, [125I]IGF-II and [125I]insulin binding
      sites in thoracic spinal cords from patients who died of amyotrophic lateral
      sclerosis (ALS) and normal controls. For these three ligands, the greatest
      amounts of specific binding were located in the deeper layers of the dorsal horn
      > intermediate zone > lamina X > ventral horn > superficial layers of the dorsal
      horn > white matter of the spinal cord. Highly significant (P < 0.001) increases
      in the density of [125I]IGF-I and [125I]IGF-II binding were apparent in various
      laminae of the cord of ALS patients with increased binding being particularly
      evident in the ventral horn and the intermediate zone. Significant (P < 0.05)
      increases were also seen in lamina X and in the dorsal horn. In contrast, no
      significant differences in [125I]insulin binding were observed between ALS and
      control spinal cords. Taken together, these data reveal significant increases in
      both [125I]IGF-I and [125I]IGF-II binding levels in the spinal cords of ALS
      patients albeit to different extents. These findings may be of relevance for
      future therapeutic strategies aimed at slowing the progression of this chronic
      neurodegenerative disease, as recently suggested by the beneficial therapeutic
      effects of an IGF-I treatment in ALS patients.

PMID- 8883944
TI  - Cloning and expression of the proteolipid protein DM20 cDNA from the brain of the
      rainbow trout, Oncorhynchus mykiss.
AB  - The myelin sheath in higher vertebrates consists predominantly of proteolipid
      protein (PLP) and its smaller isoform DM20. Mutations in the PLP gene produces
      several neurological disorders such as Pelizaeus-Merzbacher disease and the
      rumpshaker phenotype in mice. This paper describes the cloning and expression of
      DM20 from the brain of Rainbow trout. We have isolated a nearly full-length cDNA
      clone containing 1835 bp that codes for a protein of 258 amino acids. Trout DM20
      shows extensive homology with DM20 from higher vertebrates and includes the four
      hydrophobic regions that are believed to span the myelin membrane. The DM20
      transcript is expressed throughout the central nervous system of the trout but
      appears at its highest levels in the spinal cord and medulla oblongata. The
      transcript is expressed at very low levels on hatching day but increases 179-fold
      by the 5th week. Contrary to higher vertebrates, there is no switch to the PLP
      transcript in maturing trout. Moreover, the rsh mutation (186 Thr to Ile) that
      produces the rumpshaking neurological disorder in mice has no effect in trout.

PMID- 8883945
TI  - Effect of morphine on proopiomelanocortin gene expression and peptide levels in
      the hypothalamus.
AB  - Opiates have been reported to suppress POMC in the medial basal hypothalamus
      (MBH) but studies have been complicated by the fact that acutely, in the rat,
      opiates stimulate corticosterone and inhibit gonadal steroid release, which could
      both affect POMC in brain. We have therefore examined POMC gene expression and
      peptide levels in the MBH of castrated rats after 10 days of treatment with
      subcutaneous morphine or placebo pellets and after pellet removal. POMC mRNA was
      measured by solution hybridization assay and beta-endorphin (beta-EP) and alpha
      MSH were measured by RIA. In castrated male rats, the mean POMC mRNA
      concentration in the MBH was 1.67 +/- 0.11 pg/microgram RNA in the control
      animals and decreased to 1.17 +/- 0.11 pg/microgram RNA in the morphine-treated
      animals (P < 0.01). Similarly in castrated, estradiol replaced female rats, the
      mean POMC mRNA level in the MBH was 1.36 +/- 0.19 pg/microgram RNA and decreased
      to 0.82 +/- 0.08 pg/microgram RNA after morphine treatment (P < 0.05). beta-EP
      levels were not significantly different in either study. When castrated male rats
      were similarly morphine pelleted and killed either on day 10 or 2 days later
      after pellet removal, the mean POMC mRNA level again fell from 1.83 +/- 0.21 in
      the controls to 1.28 +/- 0.20 pg/microgram RNA after 10 days of morphine; 2 days
      after pellet removal levels remained suppressed at 0.80 +/- 0.08 pg/microgram RNA
      (P < 0.01). In this study the concentrations of beta-EP and alpha-MSH were both
      noted to decline in the MBH after morphine treatment (P < 0.05). When the forms
      of beta-EP in the MBH were characterized by HPLC, a decrease in the concentration
      of beta-EP was again seen after morphine but no significant differences in the
      pattern of beta-EP processing or in the relative amounts of beta-EP1-31 compared
      to beta-EP1-27 and beta-EP1-26 were noted in morphine-treated animals. There was
      also no significant effect of 10(-6)-10(-4) M morphine on basal or KCl-stimulated
      release of beta-EP or gamma 3-MSH release from the perifused rat hypothalamus in
      vitro. We conclude that morphine suppresses POMC gene expression in the
      hypothalamus of chronically treated male and female rats. Persistent changes were
      also noted during morphine withdrawal. In some cases this was accompanied by a
      fall in beta-EP peptide content. These effects were seen in castrated animals
      with and without sex steroid replacement and are thus independent of the effects
      of morphine on the pituitary-gonadal axis. These results show that opiate drugs
      modify endogenous opioid systems in the brain and provide further support for the
      hypothesis that such changes may contribute to mechanisms of opiate dependence
      and withdrawal.

PMID- 8883946
TI  - Efficient adenoviral vector-directed expression of a foreign gene to neurons and
      sustentacular cells in the mouse olfactory neuroepithelium.
AB  - Replication deficient recombinant adenoviral vectors are efficient gene transfer
      agents for postmitotic cells, including neurons and glial cells. In this paper we
      have examined the effectiveness of adenoviral vector-mediated gene transfer to
      the olfactory epithelium of adult mice. We show that Ad-LacZ, a prototype first
      generation adenoviral vector containing an expression cassette for the reporter
      gene LacZ, directs transgene expression to mature and immature olfactory neurons
      and to sustentacular cells. The technique to apply the vector to the nasal cavity
      and the amount of viral vector per mouse are important variables that determine
      the success of viral vector-mediated gene transfer to the mouse olfactory
      neuroepithelium. Slow infusion of the viral vector solution in fully
      anaesthetized mice yields the best result in terms of the number of epithelial
      cells transduced. Infection of the olfactory neuroepithelium with a moderate
      amount of viral vector (10(9) plaque-forming units (PFU)) results in transgene
      expression in many cells throughout the epithelium for 8-12 days, followed by a
      decline in transduced cells at 25 days postinstillation of the virus This
      decrement in transgene expression is consistent with the natural turnover process
      that occurs in the epithelium throughout adulthood. At high viral loads (1.3 x
      10(10) PFU) extinction of transgene expression occurs as early as 8 days
      postinjection and is accompanied by epithelial degeneration indicating that the
      vector dose used should be carefully chosen. Taken together, the current
      observations demonstrate that adenoviral vectors are effective tools to
      genetically modify the adult mouse olfactory neuroepithelium in vivo.

PMID- 8883947
TI  - Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on
      gonadotropin-releasing hormone and somatostatin gene expression in the rat brain.
AB  - Pituitary adenylate cyclase-activating peptide (PACAP) is a 38-amino acid
      polypeptide, first isolated from ovine hypothalamus, which directly stimulates
      the release of several pituitary hormones, including GH, ACTH, and LH. The
      presence of PACAP receptors in several brain areas, including the hypothalamus,
      suggests that this peptide might play a role as neurotransmitter/neuromodulator.
      We have thus investigated the effects of intracerebroventricular (i.c.v.) and
      intravenous (i.v.) injections of PACAP and the potent PACAP antagonist PACAP(6
      38) on gonadotropin-releasing hormone (GnRH) and somatostatin (SS) gene
      expression in the male rat hypothalamus. The levels of mRNA were measured at the
      cellular level by quantitative in-situ hybridization. The i.c.v. injection of
      PACAP produced a 12.5% increase in the GnRH mRNA levels, an effect which was
      completely prevented by the concomitant administration of the PACAP antagonist.
      The administration of the PACAP antagonist induced by itself a 12.9% decrease in
      the hybridization signal. The i.v. administration of the same peptides induced
      modifications in GnRH gene expression which were completely opposite to those
      produced by i.c.v. administration. In somatostatinergic neurons located in the
      periventricular nucleus, the i.c.v. injection of the peptides induced
      modification in SS gene expression which were very similar to those observed for
      GnRH gene expression, although the changes were less striking. The i.v.
      administration of PACAP or its antagonist did not induce any change in the levels
      of SS mRNA. These results then strongly suggest that PACAP might be involved in a
      positive regulation of two neuropeptides involved in the control of anterior
      pituitary secretion via central specific receptors. The inverse influence of
      PACAP on GnRH gene expression after the i.v. injection might be explained by the
      short feedback effect induced by the direct stimulation of gonadotropin hormone
      release following the systemic injection of the peptide.

PMID- 8883948
TI  - Down-regulation of the GABA receptor subunits mRNA levels in mammalian cultured
      cortical neurons following chronic neurosteroid treatment.
AB  - We have recently shown that chronic neurosteroid, 5 alpha 3 alpha, treatment
      produced down-regulation of the GABA receptor binding and function, and
      heterologous uncoupling on the GABAA receptor complex in cultured mammalian
      cortical neurons. In order to explore the underlying mechanism of these observed
      down-regulation and heterologous uncoupling phenomenon, we investigated the
      effect of chronic 5 alpha 3 alpha (1 microM; 5 days) treatment on the GABAA
      receptor subunits mRNA levels, using RNase protection assay. We found that
      chronic neurosteroid, 5 alpha 3 alpha, treatment decreased the beta- and alpha
      subunits mRNA levels while not altering the gamma 2S-subunit mRNA levels in the
      cortical neurons. The decrease in the beta-subunits mRNA levels suggests a
      decrease in the presence of the beta-subunits in the composition of GABAA
      receptors. This phenomenon may explain the down-regulation of the GABAA receptor
      binding and function. A decrease in the alpha 3-subunit mRNA level suggests a
      corresponding decrease in the alpha 3-subunit in the composition of GABAA
      receptor isoforms, relative to other isoforms. This observation may be
      responsible for the chronic neurosteroid-induced uncoupling and decreased
      efficacy. In summary, chronic 5 alpha 3 alpha treatment produced down-regulation
      of the GABAA receptor beta- and alpha-subunit mRNA levels, and these changes may
      be associated with the down-regulation, heterologous uncoupling, and decreased
      efficacy of GABAA receptor complex in the cultured mammalian cortical neurons.

PMID- 8883949
TI  - Purkinje neurons express the SERCA3 isoform of the organellar type Ca(2+)
      transport ATPase.
AB  - We report the distribution of the sarco(endo)plasmic reticulum Ca2+ ATPase 3
      (SERCA3) isoform in the rat brain. Compared to SERCA2 isoform, which is found in
      all brain regions, SERCA3 is specifically expressed in the Purkinje neurons. This
      conclusion is based on immunochemical observations using SERCA3- and SERCA2b
      specific antibodies, in-situ hybridization using SERCA3-specific oligonucleotide
      probes and single-cell reverse transcription-polymerase chain reaction (RT-PCR).
      Immunocytochemistry clearly revealed the expression of SERCA3 in the cell body
      and in the dentritic processes of the Purkinje neurons. Single-cell ratio RT-PCR
      showed that Purkinje neurons expressed 3-fold lower levels of SERCA3 mRNA
      compared to SERCA2 mRNA. SERCA3 expression is very low or absent in the rat
      cerebrum and brainstem. It is known that the SERCA3 Ca2+ pump has an
      approximately 5-fold lower affinity for Ca2+ when expressed in COS cells as
      compared to other SERCA members [15]. If this property is also valid in a
      neuronal context, the expression of the SERCA3 Ca(2+)-pump isoform could have
      important functional implications for the regulation of the cytosolic Ca2+
      concentration in Purkinje neurons.

PMID- 8883950
TI  - GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells.
AB  - Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of
      the transforming growth factor-beta (TGF-beta) superfamily, has been implicated
      in the survival, morphological and functional differentiation of midbrain
      dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus
      have utility in the treatment of various human neurodegenerative disorders.
      Mechanisms regulating expression of GDNF in normal and diseased brain as a
      possible means to increase the local availability of GDNF are only beginning to
      be explored. We have established and employed a competitive reverse transcriptase
      polymerase chain reaction (RT-PCR) to study and compare levels of expression of
      GDNF mRNA in several cell types and to investigate its regulation. GDNF
      expression was clearly evident in primary cultured astrocytes, the glioma B49 and
      C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no
      signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the
      pheochromocytoma cell line PC12, emphasizing the glial character of this factor.
      Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can
      increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF),
      and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several
      other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF
      beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA
      levels at the concentrations tested. To further explore the relationship between
      FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have
      an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor
      cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a
      prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6
      cell proliferation. Finally, these data suggest that neurotrophic actions of FGF
      2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.

PMID- 8883951
TI  - A facilitatory effect on the induction of long-term potentiation in vivo by
      chronic administration of antisense oligodeoxynucleotides against catalytic
      subunits of calcineurin.
AB  - A rise in Ca2+ concentration at postsynaptic sites provides an initial step in
      inducing both the long-term potentiation (LTP) and long-term depression (LTD) in
      the CA1 region of the hippocampus. LTP induction requires the activation of
      Ca(2+)-sensitive protein kinases following the rise in Ca2+. By contrast, the
      activity of protein phosphatase(s) appears to be critical to induce LTD. Here we
      demonstrate that inhibition of the synthesis of calcineurin A alpha and A beta,
      catalytic subunits of Ca2+/calmodulin- (CaM) dependent protein phosphatase,
      reduces the threshold of induction for commissural-CA1 LTP in anesthetized rats.
      In rats administered antisense oligodeoxynucleotides (ODNs) against calcineurin A
      alpha and A beta intraventricularly for 7 days, a brief tetanic stimulation to
      the CA3 region, which in the control case was below threshold for the induction
      of LTP, now produced a long-lasting increase in both the EPSP slope and the
      amplitude of population spike recorded from the commissural-CA1 pathway. Western
      blot analysis of calcineurin showed that the threshold reduction was accompanied
      by a selective decrease in the protein levels in the hippocampus. Thus our study
      provides direct evidence that calcineurin per se has an antagonizing role in LTP
      induction. Complementary experiments with the selective calcineurin inhibitor,
      FK506, also showed the reduction of LTP threshold in a dose-dependent manner.
      These results, together with previous studies, support the hypothesis that the
      quantitative phosphorylation level of critical intracellular proteins determines
      whether the synaptic efficacy will increase or decrease after the activity
      dependent rise in postsynaptic Ca2+.

PMID- 8883952
TI  - Demonstration of a second pharmacologically active promoter region in the NGF
      gene that induces transcription at exon 3.
AB  - Nerve growth factor (NGF) has been demonstrated to facilitate neurite outgrowth,
      rescue neurons from injury, and prevent programmed cell death in neurons.
      However, the therapeutic potential of NGF is limited by metabolic instability and
      poor CNS penetration. These limitations might be circumvented by identifying
      compounds which increase endogenous production of NGF in the brain. We sought to
      determine the site of all pharmacologically inducible promoters in the NGF gene
      using a differential analysis based on semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). Mouse L929 cells were serum deprived and NGF
      mRNA was induced by treatment with phorbol 12-myristate 13-acetate (PMA), 1,25
      dihydroxy-vitamin D3 (calcitriol) or horse serum. An increase in transcripts
      initiating at exon 1 was noted in cDNA from cells induced with all three agents.
      In addition, we also observed an increase in cDNA transcripts that initiate at
      exon 3 and do not include exons 1 and 2 (4.38 +/- 0.42, 2.56 +/- 0.05 and 3.04 +/
      0.03 fold increase over control for PMA, calcitriol and serum, respectively).
      Each of these increases was completely inhibited in the presence of actinomycin
      D, indicating that the increased levels of mRNA were due to increases in
      transcription and not mRNA stabilization. These results confirm the previous
      demonstration of a promoter for NGF near exon 1 and establish a pharmacologically
      inducible promoter in the NGF gene near exon 3 that could be targeted for
      therapeutic intervention.

PMID- 8883953
TI  - Inducible gene expression from defective herpes simplex virus vectors using the
      tetracycline-responsive promoter system.
AB  - Herpes simplex virus-based amplicon vectors have been used for gene transfer into
      cultured neurons and the adult CNS. Since constitutive expression of a foreign
      gene or overexpression of an endogenous gene may have deleterious effects, the
      ability to control temporal expression would be advantageous. To achieve
      inducible gene expression, we have incorporated the tetracycline-responsive
      promoter system into amplicon vectors and showed, both in vitro and in vivo, that
      expression can be modulated by tetracycline. Using the firefly luciferase as the
      reporter gene, maximal repression by tetracycline in hippocampal cultures was
      about 50-fold. Withdrawal of tetracycline derepressed gene expression, reaching
      maximal levels within 10-12 h. In contrast, addition of tetracycline to cultures
      without prior tetracycline exposure inhibited gene expression rapidly; luciferase
      activity was reduced to less than 8% within 24 h. In adult rat hippocampus,
      vectors expressing luciferase or the Escherichia coli lacZ were repressed by
      tetracycline 9- and 60-fold, respectively. Maximum gene expression from the
      vectors occurred 2-3 days post-infection and declined thereafter. Such decline
      impeded further induction of expression by withdrawing tetracycline. This study
      demonstrates the feasibility of incorporating a powerful inducible promoter
      system into HSV vectors. The development of such an inducible viral vector system
      for gene transfer into the adult CNS might prove to be of experimental and
      therapeutic value.

PMID- 8883954
TI  - Alterations of cAMP response element-binding activity in the aged rat brain in
      response to administration of rolipram, a cAMP-specific phosphodiesterase
      inhibitor.
AB  - Transcription factor, cAMP response element-binding protein (CREB), which is
      phosphorylated by cAMP-dependent kinase via an increase in cAMP, and regulates
      gene transcription by binding to the cAMP response element (CRE) on target genes.
      We examined age-dependent alterations in the DNA-binding activity of CREB in rat
      brain regions, and the effects of rolipram, a cAMP-specific phosphodiesterase
      (PDE) inhibitor on the CRE-binding activity by electrophoretic mobility-shift
      assay (EMSA). A marked age-dependent decrease in the CRE-binding activity was
      shown in all brain regions examined, especially in the basal forebrain, the
      striatum and the hippocampus. Furthermore, CRE-binding activities in the basal
      forebrain of both young-adult and aged rats significantly increased 2 h after
      rolipram administration (1 mg/kg, i.p.), and the rolipram treatment recovered the
      decreased CRE-binding activity in the aged rats. The saturation experiment in
      EMSA also revealed that rolipram reversed the decrease in the maximum CRE
      bindings in the basal forebrain with aging. Since the 5' upstream region of the
      rat choline acetyltransferase (ChAT) gene contains CRE, and ChAT-positive neurons
      in the basal forebrain project to the frontal cortex and the hippocampus,
      rolipram may exert its previously reported ameliorating effect on the age-related
      reductions of ChAT activities in the frontal cortex and the hippocampus by
      phosphorylating CREB in the basal forebrain with activation of cAMP-dependent
      protein kinase via inhibition of PDE.

PMID- 8883955
TI  - Gonadotropin-releasing hormone gene expression in teleosts.
AB  - Expression of multiple molecular forms of gonadotropin-releasing hormone (GnRH)
      mRNAs and GnRH peptides were examined in the brains of tilapia (Oreochromis
      mossambicus) and sockeye salmon (Oncorhynchus nerka), using in situ hybridization
      histochemistry and immunohistochemical techniques. After otherwise identical
      conditions, lesser background and stronger GnRH hybridization signals were
      observed on cryostat vs. paraffin sections. In both fresh and Bouin's-fixed
      paraffin-embedded tissues, there was a good correlation between the distribution
      of GnRH mRNA and GnRH peptide-containing cells. Although the brains of tilapia
      and the sockeye were immunoreactive to three forms of the GnRH molecule (salmon,
      mammal, chicken-II), GnRH mRNA expression was site-specific and species-specific.
      In the tilapia, ganglionic cells of the nucleus olfactoretinalis, basal
      telencephalon and the anteroventral preoptic area were immunoreactive to salmon-,
      and mammalian-GnRH peptide. Neurons of the nucleus olfactoretinalis expressed
      cichlid-GnRH I mRNA. The preoptic neurons, despite the immunoreactivity,
      expressed no hybridization signals. Midbrain neurons were immunoreactive to
      salmon-GnRH but expressed cichlid-GnRH II beta (= chicken-GnRH II) mRNA
      hybridization signals. In the sockeye, ganglionic cells along the extracerebral
      course of the nervus terminalis were immunoreactive to mammalian-, chicken-II and
      salmon-GnRH. These neurons expressed only salmon-GnRH mRNA hybridization signals.
      Intracerebral GnRH expression in the sockeye was delayed till smoltification. The
      basal telencephalon and midbrain neurons immunoreactive to salmon-GnRH, formed no
      hybridization signals with GnRH antisense probes. Oligonucleotide probes
      complementary to chicken-GnRH I and mammalian-GnRH revealed no hybridization
      signals in the tilapia and in the sockeye brain. Fibers, immunoreactive to salmon
      , mammalian-, and chicken II-GnRH were seen in close association with growth
      hormone cells. Chicken-GnRH II-immunoreactive fibers were also seen in close
      proximity to somatolactin cells in the sockeye salmon.

PMID- 8883956
TI  - Overexpression of a functional NMDA receptor subunit (NMDAR1) in baculovirus
      infected Trichoplusia ni insect cells.
AB  - For overexpression of the N-methyl-D-aspartate (NMDA) receptor subunit 1b
      (NMDAR1b), its corresponding cDNA was extended by codons for six histidine
      residues at the 3'-end, cloned into a baculovirus transfer vector and integrated
      into the viral genome. Infection of Trichoplusia ni insect cells (High FiveTM
      cells) with recombinant baculovirus resulted in the production of 126- and 105
      kDa NR 1b proteins in the cell membrane fraction. Enzymatic deglycosylation with
      PNGase F as well as infection of the insect cells in the presence of tunicamycin
      revealed that the two proteins represented the N-glycosylated and non
      glycosylated forms of NMDAR1b, respectively. The recombinant NR1b protein was
      also identified with immunocytochemical methods employing a monoclonal antibody
      which recognized the six histidine residues. The affinity of this histidine tag
      to nickel ions was used for the purification of the NR1b protein. The glycine
      binding site of the subunit was successfully identified and analyzed with the
      specific antagonist 5,7-[3-3H]dichlorokynurenate (DCKA). The observed binding
      characteristics were similar to those obtained for native NMDA receptors. Whereas
      in electrophysiological measurements a functional NMDA receptor channel could not
      be found in infected insect cells, its expression was demonstrated in the Xenopus
      oocyte system after injection of the NMDAR1b cDNA construct.

PMID- 8883957
TI  - Differential effects of clozapine and haloperidol on dopamine receptor mRNA
      expression in rat striatum and cortex.
AB  - The regulation of the dopamine (DA) receptors is of considerable interest, in
      part because treatment with antipsychotic drugs is known to upregulate striatal
      D2-like receptors. While previous studies have focused on the regulation of
      striatal DA receptors, less is known about the pharmacological regulation of
      cortical DA receptors. The purpose of this study was to examine the regulation of
      DA mRNA receptor expression in the cortex compared to the striatum following
      treatment with antipsychotic agents. Adult male Sprague-Dawley rats were injected
      daily with haloperidol (2 mg/kg/day), clozapine (20 mg/kg/day) or a control
      vehicle for a period of 14 days. Following treatment, brains were subjected to in
      situ hybridization for the mRNAs encoding the five dopamine receptors; only D1,
      D2, and D3 receptor mRNAs were detected in these regions. Haloperidol tended to
      either modestly upregulate or have no effect on dopamine receptor mRNAs detected
      in striatal structures, while clozapine generally downregulated these mRNAs. On
      the other hand, in the cortex, both drugs had striking effects on D1 and D2 mRNA
      levels. Cortical D1 mRNA was upregulated by haloperidol, but this effect was
      primarily restricted to cingulate cortex; clozapine also upregulated D1 mRNA, but
      primarily in parietal regions. Haloperidol downregulated D2 mRNA in the majority
      of cortical regions, but most dramatically in frontal and cingulate regions;
      clozapine typically upregulated this mRNA, but primarily in regions other than
      frontal and cingulate cortex. These results indicate that clozapine and
      haloperidol each have regionally-specific effects, and differentially regulate
      dopamine receptor mRNA expression in striatal and cortical regions of the rat
      brain.

PMID- 8883958
TI  - Expression of insulin receptor-related receptor in the rat brain examined by in
      situ hybridization and immunohistochemistry.
AB  - Insulin receptor-related receptor (IRR) is a member of the insulin receptor
      family. However, its endogenous ligand and physiological roles are unknown. To
      elucidate the physiological roles of IRR, an orphan receptor, in the brain, we
      examined its expression at mRNA and protein levels in the brain by in situ
      hybridization and immunohistochemistry, respectively. The expression of IRR mRNA
      in the brain was highly restricted to the forebrain including the nucleus of the
      diagonal band, medial septal nucleus, ventral pallidum, accumbens nucleus and
      caudate putamen, and the brainstem including the prepositus hypoglossal nucleus,
      medial vestibular nucleus, gigantocell reticular nucleus, paragigantocellular
      nucleus and ventral cochlear nucleus. Most IRR mRNA-positive cells in the
      forebrain but not in the brainstem were cholinergic neurons. However, most IRR
      mRNA in the forebrain and brainstem was coexpressed with that of trkA, a high
      affinity receptor for nerve growth factor. IRR-immunoreactive cell bodies were
      also detected in the forebrain and brainstem. The pattern of IRR immunoreactivity
      was similar to that of IRR mRNA. Its restricted pattern indicates that IRR plays
      unique roles in the brain, in contrast to insulin and insulin-like growth factor
      I receptors, other members of the insulin receptor family, which are widely
      expressed in the brain.

PMID- 8883959
TI  - 1,25-Dihydroxyvitamin D3 regulates the expression of the low-affinity
      neurotrophin receptor.
AB  - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is known to regulate the expression of
      neurotrophins [45,46]. Here, we report that 1,25-(OH)2D3 does not influence the
      expression of truncated or full-length forms of trkB and trkC receptors mRNAs in
      primary cultures of astrocytes and in C6 glioma cells. In contrast, low
      concentrations of 1,25-(OH)2D3 increased low-affinity neurotrophin receptor
      (P75NTR) mRNA and protein levels in C6 glioma cells. Putative vitamin D
      responsive elements (VDRE) in the P75NTR promoter have been investigated by
      transfecting plasmids containing sequences from P75NTR promoter fused to a cat
      reporter gene. A region between -610 and -860 bp upstream from the translation
      start codon was found to respond to 1,25-(OH)2D3. Interestingly, 1,25-(OH)2D3
      does not regulate P75NTR in primary cultures of astrocytes even at concentration
      as high as 10(-7) M. Since long-term treatment of 1,25-(OH)2D3 induces cell death
      in C6 glioma cells but not in primary astrocytes [41], the possible involvement
      of P75NTR in 1,25-(OH)2D3-induced cell death is discussed. Finally, in-vivo
      studies show that treatment of 15-day-old and adult rats with 1,25-(OH)2D3 leads
      to a decrease in the level of P75NTR mRNA in the spinal cord but does not
      influence its expression in dorsal root ganglion or sciatic nerve. These results
      suggest that 1,25-(OH)2D3 may have a role in the specific regulation of P75NTR in
      vivo.

PMID- 8883960
TI  - Sequence analysis of PG10.2, a gene expressed in the pineal gland and the outer
      nuclear layer of the retina.
AB  - A cDNA (PG10.2) was cloned from rat using RNA fingerprinting by arbitrarily
      primed PCR (AP-PCR). Initially, a 145-bp DNA fragment was isolated from a pineal
      specific band revealed on a sequencing gel. Riboprobes generated from the DNA
      fragment were used for hybridization histochemical and Northern analyses. Both
      techniques indicate a gene (8 kb mRNA) expressed only in the pineal gland and the
      outer nuclear layer of the retina. Two 4-kb cDNA fragments generated by 5'-RACE
      (rapid amplification of cDNA ends) and 3'-RACE were obtained using a long
      template PCR-based RACE technique. DNA sequencing revealed a single long open
      reading frame (ORF) encoding a predicted protein of 1239 amino acids, containing
      multiple motifs: a typical signal sequence of 20 amino acids at the NH2-terminus,
      a long extracellular domain with multiple potential glycosylation sites, a 31
      amino-acid transmembrane domain near the COOH-terminus and a 109-amino-acid
      cytoplasmic tail. There are also two domains similar, but not identical, to EGF
      like (epidermal growth factor-like) domains located just upstream of the
      transmembrane domain. These features suggest that this gene may encode a
      glycoprotein involved in cell adhesion, growth, and differentiation of pineal and
      retinal photoreceptor cells.

PMID- 8883961
TI  - Expression of the fibroblast growth factor family and their receptor family genes
      during mouse brain development.
AB  - The fibroblast growth factor (FGF) family is composed of nine members and four
      genes encode protein tyrosine kinase receptors for them. To gain insight into the
      involvement of FGFs and their receptors in the development of nervous system,
      their expression in brains of perinatal and adult mice was examined by semi
      quantitative reverse transcription-linked polymerase chain reactions and in situ
      hybridization. Although all the genes, with the exception of FGF-4, were found to
      be expressed, FGF-3, FGF-6, FGF-7 and FGF-8 genes demonstrated higher expression
      in the late embryonic stages than in postnatal stages, suggesting that these
      members are involved in the late stages of brain development. In contrast,
      expression of FGF-1 and FGF-5 increased after birth. Interestingly, FGF-6
      expression in perinatal mice was restricted to the central nervous system and
      skeltal muscles, with intense signals in the developing cerebrum in embryos but
      in cerebellum in 5-day-old neonates. Furthermore, FGF-receptor (FGFR)-4, a
      cognate receptor for FGF-6, demonstrated similar spatiotemporal expression,
      suggesting that FGF-6 and FGFR-4 plays significant roles in the maturation of
      nervous system as a ligand-receptor system. The results indicate that individual
      member of the fibroblast growth factor and their receptor family are expressed
      either sequentially or simultaneously in brain development, strongly suggesting
      their involvement in the regulation of a variety of developmental processes of
      brain, i.e., proliferation and migration of neuronal progenitor cells, neuron and
      glia differentiation, neurite extensions, and synapse formations.

PMID- 8883962
TI  - A conserved disulfide loop facilitates conformational maturation in the subunits
      of the acetylcholine receptor.
AB  - To examine the structural determinants for the assembly of ligand-gated
      receptors, we constructed mutant alpha, beta, gamma and delta subunits of the
      Torpedo acetylcholine receptor (AChR), lacking one of the conserved cysteine
      residues which forms a 13-amino acid disulfide loop in the amino terminal domain
      of each subunit. Mutant subunits were co-expressed with complementary wild-type
      subunits in Xenopus oocytes. Using subunit-specific antisera and monoclonal
      antibodies that recognize the two distinct alpha-bungarotoxin (alpha-BuTX) sites
      on the AChR, we were able to distinguish immature subunit associations from
      conformationally mature AChR complexes. Removal of the disulfide loop on the
      alpha subunit completely destroyed the formation of the two toxin-binding sites,
      while removal of the structure on the beta subunit had little effect. While
      mutant gamma and delta subunits were capable of forming associations (immature
      assembly) with other subunits, the formation of alpha-BTX sites between alpha and
      mutant gamma or mutant delta subunits was diminished. Interestingly, assembly of
      alpha beta gamma subunits remained efficient in the presence of mutant delta
      subunits, whereas assembly of alpha beta delta subunits was inefficient in the
      presence of mutant gamma subunits. Thus, these results indicate that the
      formation of the disulfide loop facilitates the conformational maturation of
      alpha gamma and alpha delta complexes, which may be conditional for correct
      subunit coupling in assembling receptors. Furthermore, it seems likely that the
      correct coupling between the alpha and gamma subunits is the most important step
      in subunit assembly.

PMID- 8883963
TI  - Effects of synthetic urokinase inhibitors on local invasion and metastasis in a
      murine mammary tumor model.
AB  - Urokinase-type plasminogen activator (uPA) initiates an extracellular proteolytic
      cascade with which invasive cells eliminate barriers to movement. We have
      evaluated the antiinvasive and antimetastatic properties of two recently
      developed synthetic uPA inhibitors, B428 and B623, in a BALB/c mouse mammary
      carcinoma model. We used the F3II and M3 tumor cell lines, previously described
      by our laboratory. In vitro, noncytotoxic concentrations of B428 or B623
      inhibited secreted and cell-associated uPA activity produced by tumor cells and
      blocked uPA-mediated whole tumor cell degradation of fibronectin, allowing
      deposition of extracellular fibronectin fibrils. In vivo, administration of
      compounds was not associated with overt toxic effects. Daily i.p. treatment with
      B428 (20 mg/kg/day) or B623 (7.5 mg/kg/day) for 2 weeks, beginning after tumor
      take, markedly blocked the invasion of the muscle and adipose layers of the
      subcutis and dermis in mice bearing highly invasive F3II tumors. However, these
      compounds neither inhibited tumor-induced angiogenesis nor reduced the incidence
      of spontaneous lung metastasis. Moreover, B623 enhanced the formation of
      experimental lung metastasis. Our results suggest that synthetic uPA inhibitors
      act as potent antiinvasiveness agents in vivo but may be unable to control
      progression of the metastatic disease in the present mammary tumor model.

PMID- 8883964
TI  - Male breast cancer: an 11 year review of 66 patients.
AB  - A review was conducted of 66 men with carcinoma of the breast seen at this
      institution between 1981 and 1992. The results of the study suggest that there
      are many similarities between breast cancer in men and women. The most common
      clinical presentation was a lump in the breast. The majority of tumors were T1 or
      T2, and infiltrating ductal carcinoma was the predominant histological type.
      Axillary nodal status and histological grade were predictive of survival. The
      pattern of recurrence and survival rates were similar to those seen in women.
      Some differences, however, were evident. Tumors were centrally located in the
      majority of patients and there was a high frequency of nipple involvement. The
      hormone receptor positivity rate was high and the median age at presentation was
      older. In comparison to a previous report of the same disease from this
      institution 10 years ago, fewer patients underwent radical surgical procedures
      and more patients received adjuvant systemic therapy. These approaches are
      justified since there are many biological similarities between breast cancer in
      men and women.

PMID- 8883965
TI  - Tamoxifen aziridine labeling of the estrogen receptor-potential utility in
      detecting biologically aggressive breast tumors.
AB  - Expression of estrogen receptor (ER) is a helpful predictor of response to
      endocrine therapy and disease free survival in breast cancer patients. The
      presence of variant estrogen receptors has been demonstrated at the RNA/DNA level
      and might represent an escape of tumors from hormonal control mechanisms.
      However, the demonstration that the corresponding peptides do exist is a real
      challenge. Denaturing polyacrylamide gel electrophoresis (SDS-PAGE) of covalently
      bound [3H]tamoxifen aziridine ([3H]TAZ) to ER demonstrates a specific, multiband
      peptide pattern recognized by anti-ER monoclonal antibodies (anti-ER Mo Abs). The
      native 66 kDa ER form identified through its hormone binding domain by the H-222
      Mo Ab was the most prominent one followed by 50, 35, and 28 kDa forms on
      fluorography. Such patterns from early human breast tumors were compared to the
      ones of more advanced disease, namely large primary breast cancers, metastatic
      lymph nodes, and soft tissue relapses: in these cases, molecular forms of 43 and
      35 kDa were identified with a remarkable consistency. The 43 kDa peptide was more
      frequently identified by the H-226 Mo Ab (which maps a region near the DNA
      binding domain)-albeit with low labeling intensity as compared to H-222 Mo Ab. In
      addition, the 43 kDa peptide was inversely correlated to ER levels. This altered
      ER or related peptide could potentially be a marker of biologically aggressive
      breast tumors.

PMID- 8883967
TI  - Prognostic significance of serum c-erbB-2 protein in breast cancer patients.
AB  - The tissue expression of c-erbB-2 protein in breast cancer is a marker of poor
      prognosis in a number of studies. More recently it has also been suggested that c
      erbB-2 expression may predict response to systemic therapy in patients with
      advanced breast cancer. The measurement of c-erbB-2 protein in the serum of
      breast cancer patients has now been reported, but the significance of this
      finding is not clear. In this study an ELISA assay was used to measure c-erbB-2
      in the sera of 23 normal controls, 46 benign breast disease patients, and 119
      breast cancer patients. Elevated serum c-erbB-2 protein levels were detected in
      13% (3/23) of normal controls, 15% (7/46) of benign disease patients, 15% (7/46)
      of Stage I/II patients, 26% (9/35) of Stage III patients, and 21% (8/38) of Stage
      IV patients. The tissue expression of the c-erbB-2 protein showed no association
      with detection of the serum c-erbB-2 protein (p = 0.31). In the 67 Stage III and
      IV patients who had assessable disease the presence of the c-erbB-2 protein in
      the serum bore no relationship to response to hormonal therapy (p = 0.71). Serum
      detection of the c-erbB-2 protein in Stage I/II patients predicted for a
      worsening of both survival outcome (p = 0.002) and disease free interval (p =
      0.002). A worse outcome was also seen for the Stage III patients (p = 0.04) and
      Stage IV patients, although the latter did not reach statistical significance (p
      = 0.27). This study found that the presence of c-erbB-2 in the serum of breast
      cancer patients was of prognostic significance for all stages of disease.

PMID- 8883966
TI  - Sex steroid receptor expression in 'carcinoid' tumours of the breast.
AB  - Nine 'carcinoids' of the breast (argyrophilic carcinomas) were examined for the
      presence of estrogen receptor (ER), progesterone receptor (PR), and androgen
      receptor (AR), using immunohistochemistry. The tumours were selected on the basis
      of their histo-morphological appearance and positive Grimelius stain. All cases
      were immunoreactive for neuron-specific enolase (NSE). In one case the tumour
      cells were intensely chromogranin A positive. All cases were ER positive, while 5
      cases expressed AR and 5 cases PR. Immunostaining for ER and simultaneous
      demonstration of argyrophilia or chromogranin A expression in chromogranin A
      positive argyrophilic carcinoid tumour of the breast provided further evidence
      that neuroendocrine cells in breast tumours express sex steroid receptors. The
      similarity in sex steroid receptor expression pattern in 'carcinoids' of the
      breast and the more common categories of breast cancer suggests an identical
      responsiveness to endocrine therapy.

PMID- 8883968
TI  - Quantification of uPA receptor expression in human breast cancer cell lines by
      cRT-PCR.
AB  - The conversion of plasminogen to active plasmin is thought to be a crucial step
      in the process of extracellular matrix degradation associated with metastatic
      spread. Activation of plasminogen is initiated by urokinase plasminogen activator
      (uPA). The binding of uPA to the uPA cell surface receptor (uPA-R) accelerates
      plasmin generation from plasminogen and localizes uPA activity to the cell
      surface. We investigated the mRNA-expression of uPA-R in 19 different human
      breast cancer cell lines. In a competitive reverse transcription polymerase chain
      reaction (cRT-PCR) we simultaneously co-amplified two different RNA templates
      bearing the same primer recognition sequences, the cell line RNA and a known
      amount of an in vitro synthesized uPA-R-RNA internal standard. We analyzed the
      two PCR products differing 50 bp in size by agarose gel electrophoresis and
      calculated the initial uPA-R-RNA template concentration from the relative
      intensities of the bands quantified by video densitometry. We grouped the
      investigated cell lines according to their in vitro invasiveness according to
      literature. Cell lines with a high potential of invasiveness showed a higher
      expression of uPA-R compared to those with a low potential of invasiveness
      (Student's t-test, p 0.04). In addition to that we compared the uPA-R mRNA levels
      with uPA-R, uPA, and PAI-1 protein levels in culture supernatants and cell
      lysates. The obtained results in breast cancer cell lines with different
      invasiveness and in benign epithelial cell lines revealed the complex cooperation
      of the urokinase type proteolytic pathway. uPA, uPA-R, and PAI-1 are to be
      considered as a diagnostic tool rather than assaying a particular molecule alone.
      Our findings support the hypothesis that the urokinase proteolytic pathway plays
      a central role in the acquisition of an invasive phenotype and favors its
      potential use as a prognostic marker in patients with breast cancer.

PMID- 8883969
TI  - Effects of tamoxifen on serum lipid and apolipoprotein levels in postmenopausal
      patients with breast cancer.
AB  - Serum lipids and apolipoprotein levels were measured in twenty postmenopausal
      women with primary breast cancer, before and three months after tamoxifen therapy
      (10 mg twice a day). Tamoxifen caused a significant reduction in total serum
      cholesterol (10%; P < 0.02), and in low-density lipoprotein cholesterol (17%; P <
      0.01), and a significant 47% increase in the subclass 2 of the high density
      lipoprotein cholesterol (P < 0.01). In addition, tamoxifen caused a 16% increase
      in apolipoprotein A-I, a 12% decrease in apolipoprotein B (P < 0.05), and a 37%
      reduction in the serum concentration of lipoprotein (a) (P < 0.01). These results
      show that tamoxifen brings about an important improvement in serum lipid profile.

PMID- 8883970
TI  - Amplifications of oncogene erbB-2 and chromosome 20q in breast cancer determined
      by differentially competitive polymerase chain reaction.
AB  - A new method of measuring gene copy number in small samples of DNA was used to
      measure amplification of the erbB-2 gene and of chromosome 20q in breast cancer.
      This method, termed 'differentially competitive polymerase chain reaction' (DC
      PCR) combines the advantages of two other techniques for measuring amplification
      by PCR, namely differential PCR and competitive PCR. The DC-PCR methodology was
      evaluated for sensitivity and specificity by comparing amplification of erbB-2
      measured by DC-PCR with that obtained by fluorescence in situ hybridization
      (FISH) for 42 cases or Southern blotting and/or slot blot analysis for 34 cases.
      There was over 90 percent concordance with both FISH and Southern blotting and/or
      slot blot analysis. DC-PCR was used to further characterize the newly described
      amplicon at chromosome 20q. By analyzing DNA from 10 breast cancer cell lines at
      7 different loci, we identified a potential common region of amplification of
      approximately 5 centimorgans at chromosome 20q13 bordered by loci D20S52 and
      RMC20C100-S1. One hundred and seventeen cases of primary breast cancer were
      evaluated for amplification at these two loci. Amplification at one or more loci,
      defined as > 1.5 fold higher copy number than that of normal DNA, was found in 25
      cases (21%). Sixteen cases were amplified at only one of the two probes (12 cases
      for RMC20C001-S1 and 4 cases for D20S52), suggesting that the target gene lies
      between the two markers or that there are two independent target genes within a
      small chromosome region.

PMID- 8883972
TI  - AIDS research and prevention: a social representational approach.
AB  - The KABP paradigm (knowledge-attitude-belief-practice) dominates social
      scientific AIDS research and prevention programmes. This paper questions a number
      of the assumptions of the paradigm both theoretically and empirically. Having
      discussed a number of the paradigm's shortcomings, an alternative, a social
      representational approach, is proposed. The choice of an alternative approach is
      guided by theoretical concerns but its efficacy is demonstrated by way of a cross
      cultural analysis of data. By way of contrast to the KABP paradigm, the
      methodology of the social representational approach calls for the sampling of the
      social representations held by individuals in parallel with those which circulate
      in their social environment. In addition, the alternative approach highlights the
      importance of identity and of emotional factors in AIDS-related thought and
      action. The shift in theory and methodology which is proposed provides an altered
      focus for efforts to control the spread of HIV.

PMID- 8883971
TI  - Diagnosis of axillary lymph node metastases in patients with breast cancer.
AB  - The diagnosis of axillary (AX) metastases remains a challenge in the management
      of breast cancer and is a subject of controversy. Clinical node staging clearly
      is limited in the assessment of AX lymph nodes. AX mammography, ultrasonography,
      and computed tomography (CT) do not provide histologic information. Although
      nuclear magnetic resonance imaging may have considerable value in the diagnosis
      of AX metastases, it does not detect micrometastases. The use of biologic markers
      in the assessment of AX metastases remains a subject of investigation. On the
      other hand, biopsy of selected AX nodes or tissue with examination of histology
      or cytology generally would not identify a significant percentage of patients
      with AX node involvement. Sentinel lymph node biopsy, however, might be
      potentially useful for assessing AX metastases, although it remains
      investigational. In order to simplify diagnosis and reduce morbidity and
      mortality, alternatives to AX dissection must be sought and imaging and staging
      modalities refined. We present a review of the literature pertaining to the
      diagnosis of AX metastases in patients with breast cancer and a discussion of
      some current areas of controversy.

PMID- 8883974
TI  - The 'Zar' possession syndrome among Ethiopian immigrants to Israel: cultural and
      clinical aspects.
AB  - This article describes a cultural pattern related to altered states of
      consciousness, observed amongst new immigrants from Ethiopia in Israel. The
      belief in possession by Zar spirits is one of the most common possession
      phenomena in Africa and in other continents. Possession by Zar is expressed by a
      wide range of behaviours, such as involuntary movements (often resembling
      epileptiform convulsions), mutism and incomprehensible language. Such behaviour
      can be misinterpreted as representing symptoms of neurologic or psychiatric
      disorders. Such misinterpretation has led to inappropriate psychiatric admissions
      and to misdiagnosis of such cases as major psychiatric disorders. The article
      illustrates the Zar phenomenon by three clinical vignettes and discusses its
      cultural and anthropological aspects, as well as its clinical implications within
      a Western society.

PMID- 8883973
TI  - Clinical decision making in intake interviews for psychotherapy: a qualitative
      study.
AB  - The present paper is based on a study, carried out in an institute for
      psychotherapy, of intake workers' appraisals of encounters with their clients
      during intake interviews for psychotherapy. The main purpose of the study was to
      gain insight into the factors determining intake workers' perceptions of
      encounters with their clients. The presumed relationship between the perception
      of clients and the formulation of specific proposals for treatment by intake
      workers was an additional point of interest. Four intake workers were interviewed
      by the first author. Each intake worker described his or her encounter during the
      intake with two separate clients. A semi-structured qualitative interview format
      and a qualitative method of response analysis were used. A consistent
      relationship was found between the client's mode of selfpresentation as perceived
      by the intake worker and the formulation of a specific proposal for treatment.
      The most conspicuous distinction found was that between the proposal of either
      deep insight-oriented therapy or supportive therapy and the client's perceived
      ability or relative inability to be genuinely open emotionally, and get to the
      core of his or her problems as presented. Further research will be necessary to
      corroborate the findings described.

PMID- 8883975
TI  - Personal hopefulness: a conceptual review of the relevance of the perceived
      future to psychiatry.
AB  - Personal hopefulness, along with the perceived future, has been overlooked by
      psychiatry until relatively recently. There are cogent reasons why psychiatry
      should not ignore developments in relation to hope. Concepts related to hope are
      examined to delineate the components of the perceived future. Hope is defined in
      terms of its elements, its objects, its subject, its phenomenology and its
      relationship to despair and reality. The contribution of hope to our
      understanding of psychiatric and medical disorder and recovery from mental
      illness are also considered, with special reference to existing notions of
      depression and anxiety. Institutionalization is characterized as a disorder of
      personal hopefulness. Implications for potential shifts in current theoretical
      formulation and practice are anticipated. In particular, a critique of the
      learned helplessness/optimism formulation is outlined.

PMID- 8883976
TI  - An episode of syncope attacks in adolescent schoolgirls: investigations,
      intervention and outcome.
AB  - An increasing number of students in a secondary convent girls school developed
      syncope attacks over a time course of about two months. Fourteen students who
      suffered from syncope and 12 other students from the same class with no symptoms
      were assessed by a team of psychologists and paediatricians with the aim of
      identifying the cause of the problem and to formulate possible remedial action.
      Psychological assessments included a mental state examination, developmental,
      personal and psychological history, state-trait anxiety, self-esteem, hypnotic
      suggestibility, and students' beliefs about the cause and nature of the syncope
      attacks. Physical investigations included physical examination, blood pressure
      and electrocardiogram. The results indicated that most participants and controls
      had no physical or psychological pathologies. The two groups were not different
      on the physical and psychological measures. Analyses of the interview data,
      however, indicated that all the syncope sufferers belonged to a cohesive and
      exclusive social network. Social psychological circumstances rather than
      individual psychopathology were noted to be primarily responsible for the spread
      and maintenance of the mass hysterical influence. Intervention consisted of
      health education, authoritative reassurance and back-up support. Follow-up
      assessment after three and 12 months indicated no further syncope episodes.

PMID- 8883977
TI  - Pain patients' bias in the interpretation of ambiguous homophones.
AB  - This study describes an investigation into the interpretation of ambiguous
      homophones by chronic pain patients and non-pain control patients. Participants
      were presented auditorily with a list of homophones and asked to write down the
      word they had just heard. Following a two-minute distraction task they completed
      a free-recall task. A significant bias towards pain interpretation was exhibited
      by the pain patients and this effect appears to be independent of anxiety and
      depression. Both groups reported awareness of the ambiguity of some words, and
      the analysis was repeated for each participant excluding the words reported to be
      ambiguous. Pain patients still showed the bias towards pain interpretation. The
      free-recall task also demonstrated a memory bias for pain stimuli in pain groups.
      The results provide further evidence that chronic pain is associated with biases
      in the processing of information. Future research should aim to investigate the
      role of these biases in the maintenance of chronic pain.

PMID- 8883978
TI  - Daily events and somatic symptoms: evidence of a lagged relationship.
AB  - In order to examine the lagged relationship between daily events and somatic
      symptoms, 48 students completed the Students Assessment of Daily Experience
      Questionnaire and the Somatic Symptoms subscale of the General Health
      Questionnaire for five days. Undesirable events were correlated with somatic
      symptoms three to four days later.

PMID- 8883979
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- 8883980
TI  - History of the Medical Library Association's credentialing program.
AB  - Since the Medical Library Association (MLA) adopted the Code for the Training and
      Certification of Medical Librarians in 1949, MLA members have reviewed and
      revised the program regularly. This paper traces the history of MLA's
      professional recognition program to illustrate how the program has changed over
      time and to identify the issues that have surrounded it. These issues include the
      value of the program to individual members, cost to MLA, appropriate entry
      requirements, certification examinations, and recertification requirements. The
      development and operation of MLA's current credentialing program, the Academy of
      Health Information Professionals, is described in detail.

PMID- 8883981
TI  - Health sciences library building projects: 1995 survey.
AB  - The Medical Library Association's fifth annual survey of recent health sciences
      library building projects identified twenty-five libraries planning, expanding,
      or constructing new library facilities. None of the fifteen new library projects
      are free standing structures; however, several occupy a major portion of the
      project space. Ten projects involve renovation of or addition to existing space.
      Information regarding size, cost of project, type of construction, completion
      date, and other factual data was provided for twelve projects. The remaining
      identified projects are in pre-design or early-design stages, or are awaiting
      funding approval. Library building projects for three hospital libraries, three
      academic medical libraries, and an association library are described. Each
      illustrates how considerations of economics and technology are changing the
      traditional library model from a centrally stored information depository housing
      a wide range of information under one roof where users come to the information,
      into an electronic model gradually shifting from investment in the physical
      presence of resources to investment in creating work space for creditible
      information specialists who help in-house and distanced users to obtain
      information electronically from any place and at any time. This new model
      includes a highly skilled library team to manage, filter, and package the
      information to users trained by these resident experts.

PMID- 8883982
TI  - The image of health sciences librarians: how we see ourselves and how patrons see
      us.
AB  - A survey was conducted to solicit data related to health professionals image of
      librarians. Physicians, residents, nurses, medical students, dentists,
      pharmacists, physical therapists, and occupational therapists were questioned
      about their experiences with and opinions of librarians, particularly the skills
      and characteristics needed by helpful, successful librarians. Health sciences
      librarians were also questioned about their own professional image and their
      perceptions of their patrons' impression of librarians. Librarians and health
      professionals alike ranked good communication as the most important skill for
      librarians. Computer or technological skills were ranked fourth by librarians but
      second by health professionals. Although librarians tended to describe themselves
      in slightly more positive terms than did their patrons, health professionals
      viewed librarians as approachable, responsive, supportive, and open to change.
      Health professionals also reported that they received accurate, reliable, and
      timely information from librarians and that this information was valuable.

PMID- 8883983
TI  - Beyond relevance--characteristics of key papers for clinicians: an exploratory
      study in an academic setting.
AB  - OBJECTIVE: The purpose of this study was to determine what factors beyond
      relevance influence a clinician's decision to choose to read one journal article
      over another in satisfying an information need. DESIGN: Seventeen health care
      providers were interviewed and then surveyed regarding the characteristics of key
      articles (those they would not want to miss). On a Likert scale, the clinicians
      graded forty-two characteristics for importance in the decision process.
      Relevance was assumed and not at issue. SETTING: The study took place in an
      academic health science center. SUBJECTS: The subjects were seventeen clinicians,
      all with patient care responsibilities. There were four internists, four
      surgeons, three family practitioners, three pediatricians, two psychiatrists, and
      one clinical psychologist. RESULTS: Factors beyond relevance that most often
      influenced the decision process pertained to methodological rigor, authors and
      their institutional affiliations, document types, and population studied.
      CONCLUSIONS: Among the clinicians surveyed, factors beyond topicality influenced
      judgments as to what constitutes an important article. The emphasis respondents
      gave to certain attributes is echoed in other published work and highlights the
      need for more intensive investigation of these non-subject indicators as search
      parameters. Improved searching capabilities might well lead to a significant
      reduction in the clinician's information overload.

PMID- 8883984
TI  - A comparison of authors publishing in two groups of U.S. medical journals.
AB  - This study compared the editorial peer review experiences of authors who
      published in two groups of indexed U.S. medical journals. The study tested the
      hypothesis that after one journal rejects a manuscript an author selects a less
      well-known journal for submission. Group One journals were defined as those
      indexed in 1992 MEDLINE that satisfied several additional qualitative measures;
      Group Two journals were indexed in the 1992 MEDLINE only. Surveys were sent to
      the first authors of 616 randomly selected articles, and 479 surveys were
      returned, for a response rate of 78.1%. A total of 20.8% of Group One and 15.7%
      of Group Two articles previously had been rejected. Group One authors were more
      likely to select a journal for its prestige and article quality, while Group Two
      authors were more likely to have been invited to submit the manuscript. More than
      60% of both groups felt the peer review had offered constructive suggestions, but
      that it had changed article conclusions less than 3% of the time. Both groups
      thought the review process only marginally improved content, organization, or
      statistical analysis, or clarified conclusions. Between 3% and 15% of all authors
      received considerable conflicting advice from different reviewers. Authors from
      both groups differed as to their reasons for journal selection, their connections
      with the publishing journal, and patterns of resubmission after rejection.

PMID- 8883985
TI  - Medical problem attributes and information-seeking questions.
AB  - This study was designed to explore the relationship between certain attributes of
      a diagnostic problem and a particular information-seeking question. Using case
      vignettes under experimental conditions, fifty residents in internal medicine and
      family practice informed the experimenter of the most important thing they would
      need to know to make a preliminary diagnosis. These data were classified
      nominally using a preexisting taxonomy. Significant results indicated that
      Quantification questions tend to be asked under urgent conditions and
      Verification questions tend to be asked when the least amount of information is
      presented. While the taxonomy used to classify the questions did not prove rich
      enough to describe information needs fully, results did suggest some consistency
      in question asking, a skill that could be developed further during medical
      education.

PMID- 8883986
TI  - Clinical extracts of biomedical literature for patient-centered problem solving.
AB  - This paper reports on a four-part qualitative research project aimed at designing
      an online document surrogate tailored to the needs of physicians seeking
      biomedical literature for use in clinical problem solving. The clinical extract,
      designed in collaboration with three practicing physicians, combines traditional
      elements of the MEDLINE record (e.g., title, author, source, abstract) with new
      elements (e.g., table captions, text headings, case profiles) suggested by the
      physicians. Specifications for the prototype clinical extract were developed
      through a series of relevance-scoring exercises and semi-structured interviews.
      For six clinical questions, three physicians assessed the applicability of
      selected articles and their document surrogates, articulating relevance criteria
      and reasons for their judgments. A prototype clinical extract based on their
      suggestions was developed, tested, evaluated, and revised. The final version
      includes content and format aids to make the extract easy to use. The goals,
      methods, and outcomes of the research study are summarized, and a template of the
      final design is provided.

PMID- 8883987
TI  - Population groups: indexing, coverage, and retrieval effectiveness of ethnically
      related health care issues in health sciences databases.
AB  - OBJECTIVES: This study examined methods of accessing (for indexing and retrieval
      purposes) medical research on population groups in the major abstracting and
      indexing services of the health sciences literature. DESIGN: The study of
      diseases in specific population groups is facilitated by the indexing of both
      diseases and populations in a database. The MEDLINE, PsycINFO, and Embase
      databases were selected for the study. The published thesauri for these databases
      were examined to establish the vocabulary in use. Indexing terms were identified
      and examined as to their representation in the current literature. Terms were
      clustered further into groups thought to reflect an end user's perspective and to
      facilitate subsequent analysis. The medical literature contained in the three
      online databases was searched with both controlled vocabulary and natural
      language terms. RESULTS: The three thesauri revealed shallow pre-coordinated
      hierarchical structures, rather difficult-to-use terms for post-coordination, and
      a blurring of cultural, genetic, and racial facets of populations. Post
      coordination is difficult because of the system-oriented terminology, which is
      intended mostly for information professionals. The terminology unintentionally
      restricts access by the end users who lack the knowledge needed to use the
      thesauri effectively for information retrieval. CONCLUSIONS: Population groups
      are not represented adequately in the index languages of health sciences
      databases. Users of these databases need to be alerted to the difficulties that
      may be encountered in searching for information on population groups. Information
      and health professionals may not be able to access the literature if they are not
      familiar with the indexing policies on population groups. Consequently, the study
      points to a problem that needs to be addressed, through either the redesign of
      existing systems or the design of new ones to meet the goals of Healthy People
      2000 and beyond.

PMID- 8883988
TI  - Library services for people with disabilities: results of a survey.
AB  - The Americans with Disabilities Act (ADA), enacted in 1990, has had a significant
      impact on the way many institutions, including libraries, do business. The
      Association of Research Libraries surveyed its members in 1991 to determine the
      effect of this legislation, and the author conducted a similar survey in 1995 to
      learn what progress academic health sciences libraries have made in serving the
      needs of people with disablities. A questionnaire was mailed to 131 members of
      the Association of Academic Health Sciences Library Directors. Nearly three
      quarters of respondents reported elimination of physical barriers. The most
      common services provided are retrieval of materials from the stacks and photocopy
      assistance. Much less attention has been paid to the use of adaptive technology
      that allows disabled users to search a library's online catalog and databases;
      special technology is often provided by another unit on campus but there seems to
      be little coordination with library services Few libraries have assigned
      responsibility for disability services to a specific staff member and even fewer
      have done a formal assessment of the need for special services. The issues
      identified by the survey should challenge academic health sciences libraries to
      examine their status regarding compliance with ADA legislation.

PMID- 8883989
TI  - Where should the pharmacy researcher look first? Comparing International
      Pharmaceutical Abstracts and MEDLINE.
AB  - This study compared the usefulness of various CD-ROM versions of International
      Pharmaceutical Abstracts (IPA) and MEDLINE for pharmacy research. Journal
      coverage as well as the strengths and weaknesses of database structure and
      contents were considered. The journals indexed in each database were compared to
      those identified in a survey of the research journals most important to
      University of Maryland at Baltimore pharmacy faculty and in a similar North
      Carolina study rating pharmacy journals. In addition, indexed journals were
      checked against the Institute for Scientific Information's most recent list of
      high-impact journals in pharmacology and pharmacy. Searches representing a
      variety of topics relevant to pharmacy were conducted in both databases, and the
      number and relevance of citations located were analyzed. Results showed that IPA
      indexed a greater number of pharmacy titles, but that MEDLINE indexed more
      pharmacy journals designated in studies as significant to the field. There was
      little overlap in coverage between the two databases. MEDLINE produced larger
      retrievals for the majority of questions, but many citations retrieved in IPA did
      not appear in MEDLINE.

PMID- 8883990
TI  - Learning to use the Internet: an interactive team-taught workshop for dental
      faculty and staff.

PMID- 8883991
TI  - Faculty involvement in problem-based library orientation for first-year medical
      students.

PMID- 8883992
TI  - Teaching roles of librarians in nursing education.

PMID- 8883993
TI  - Author characteristics in three medical library periodicals.

PMID- 8883994
TI  - Academic health sciences librarians' use of the Brandon-Hill selected list in
      book selection activities: results of a preliminary descriptive study.

PMID- 8883995
TI  - Librarians and collaborative research: toward a better scientific base for
      information practice.

PMID- 8883996
TI  - A role in cyberspace for prospective indexing.

PMID- 8883997
TI  - J. Michael Homan, twenty-second editor of the Bulletin.

PMID- 8883998
TI  - Naomi C. Broering Medical Library Association President 1996-1997.

PMID- 8883999
TI  - Enhancing the quality and usefulness of epidemiological studies of burn injuries.
AB  - The objectives of this manuscript are to highlight how certain features of
      epidemiological studies of burn injuries affect the quality of the investigation
      and the usefulness of the results, and to suggest a framework, in the form of a
      checklist, for future submissions of epidemiological studies to Burns.

PMID- 8884000
TI  - Epidemiology and mortality of 162 major burns in Kuwait.
AB  - The burns intensive care unit at IBN Sina Hospital reopened in July 1991,
      following the Iraqi occupation of Kuwait and the Gulf War. Epidemiology and
      mortality of 162 burn patients with 30 per cent and over total body surface area
      (TBSA) burns, treated from July 1991 to December 1994, is presented. There were
      91 males and 71 females with a ratio of 1.3 to 1. The median age was 30 years
      (range 4 months to 93 years) and 44 per cent of the patients were 15-40 years of
      age. 124 (76.5 per cent) accidents occurred at home and the flame burn was the
      commonest involving 131 (80.9 per cent) patients. The median burn surface area
      was 45.5 per cent and the majority of them sustained deep burns. The hospital
      stay of the surviving patients ranged from 11 to 174 days (median 38 days), while
      the day of the death was from 1 to 134 days. Forty-six deaths represent an
      overall mortality rate of 28.4 per cent amongst our patients. All the patients
      whose Baux score was 130 and above died. Burn shock was responsible for 10
      deaths, and out of them eight were not actively resuscitated due to high Baux
      score. Sixteen deaths occurred within 48 h postburn. Septicaemia and its related
      effects were responsible for the majority of the deaths.

PMID- 8884001
TI  - Epidemiology of burns in a district hospital in western India.
AB  - In a prospective study, data on 175 patients treated between June 1993 and
      February 1994 has been analysed. In this series, adolescents and young adults (11
      40 years) comprised 79.4 per cent of the patients. Males formed 43 per cent and
      females 57 per cent of the total burns 92 per cent of the burns occurred at home.
      86.8 per cent of the patients belonged to low socioeconomic groups. 47.4 per cent
      of them were housewives or housemaids. 44.6 per cent of burns occurred during the
      morning hours from 6 a.m. to 12 noon. 79.4 per cent of the burns were accidental
      in nature. Flame burns accounted for 92 per cent, scalds for 5.7 per cent of the
      total. 64.5 per cent of the patients were admitted within 4 h of injury. The
      overall mortality rate was 56.5 per cent, below 40 per cent surface area burned
      (%BSAB) it was 6.1 per cent and above 70 per cent it was 100 per cent. Flame
      burns resulted in maximum deaths (86.1 per cent). 40 per cent of the patients had
      more than 70 per cent BSAB burns in this series, which accounts for the high
      mortality.

PMID- 8884002
TI  - Mechanical properties of normal skin and hypertrophic scars.
AB  - The non-linear viscoelastic properties of skin tissue were characterized by
      modulus of elasticity E, which represents stiffness, and percentage extension
      (strain, xi) at load intensities of 20, 40 and 100 gm. The latter property is a
      measure of the extensibility for both normal skin and hypertrophic scar. A quasi
      static extensometer applies a standard rate of extension to the skin and its
      mechanical properties were obtained from 15 Chinese patients with burn injuries
      of superficial to full skin thickness burns. Clinical evaluation of hypertrophic
      scar is qualitative and depends on colour, thickness and hardness or firmness.
      Using mechanical properties assists in the characterization by providing a
      quantitative indicator. Higher scar grading is synonymous with increased
      stiffness and decreased extensibility. Correlation with clinical assessment was
      achieved with these in vivo viscoelastic properties.

PMID- 8884003
TI  - The hypertrophic scar and microcirculation properties.
AB  - Blood-flow measurements of microcirculation were used as a quantitative indicator
      for scar assessment and healing. A laser doppler flowmeter (LDF), giving an
      integrated instantaneous flux value through a measured volume of skin, was used
      for the measurements. It has been postulated that the degree of hypertrophy after
      thermal injury correlates with the degree of microvascular regeneration. This
      study looked quantitatively at microcirculation in normal and scarred skin of
      different clinical grading and investigated the comparative responses to changes
      in local temperature stimuli. An attempt is made to define microcirculation using
      the parameters of Vasodilation Index (Dli) and Vasomotion Intensity (% Vsm) as
      respective responses to a rise in local temperature of the skin from 36 degrees C
      to 44 degrees C. The improvements in both Dli and % Vsm with healing of scar
      relate to the degree of microvascular regeneration, which in turn correlates with
      the clinical assessment.

PMID- 8884004
TI  - Scar management of cultured epithelial autograft.
AB  - Since the introduction of cultured epithelial autograft (CEA) for the treatment
      of burns wounds, the resulting scar has caused a great deal of concern. When CEA
      is applied to a deep wound the resulting scar is subject to breakdown with
      minimal trauma. It takes a considerable period of time, in some instances years,
      before the dermal-epidermal junction matures and the skin is able to endure the
      wear and tear of normal existence. Therefore it is understandable that the
      introduction of pressure garments for treating into these scars has been somewhat
      delayed. However, we believe that early aggressive pressure therapy is the
      treatment of choice in those cases where there is a strong chance of the scar
      becoming hypertrophic. This paper presents an approach to the problems of scar
      management with CEA, not only for the case of a major full-thickness burn, but
      also for a lesser burn injury. The concept of a hydrophobic fabric as a lining
      garment is introduced. The garment design has been changed, to pay particular
      attention to reduction of shearing forces and dissipation of pressure. The
      development of our hydrophobic pressure garment is beneficial as it both reduces
      surface maceration and shearing injury. Since it protects the fragile CEA, formal
      pressure management can be instituted early in the treatment programme.

PMID- 8884005
TI  - Current difficulties and the possible future directions in scar assessment.
AB  - The quantitative assessment of the results of burn management is notoriously
      difficult. With the focus changing from survival to cosmetic and functional
      outcome, the scar assessments are increasingly important. The scar is a sum of
      the injury and all subsequent interventions on the way to healing. As such it is
      a complex structure, abnormal in its colour, depth, contour and pliability. To
      develop a quantitative system we believe it is vital to be able to track
      accurately an area of injury through time. Further, that physiological data
      acquired by a number of measurement tools be fused accurately to the
      morphologically correct information.

PMID- 8884006
TI  - Implication of basement membrane development on the underlying scar in partial
      thickness burn injury.
AB  - There is increasing evidence from the scientific literature that the developing
      epithelial basement membrane has the potential to influence the underlying
      dermis. The most rapidly dividing and active cell within the skin complex is the
      basal cell of the epidermis. The basal cell is well known to produce numerous
      protein factors which influence cellular growth and differentiation. The
      underlying dermal fibroblasts, by comparison, are relatively static. The concept
      that basal cells have an influence on the dermal and overall skin environment via
      the extracellular expression of proteins in the extracellular matrix, is gaining
      increased interest. A hypertrophic scar is a dermal phenomenon resulting from an
      imbalance in collagen production and maturation. Although the collagen is
      produced by the fibroblast, the extracellular matrix is an area where the
      epidermal cells have a potential influence. It is therefore the purpose of this
      paper to explore the idea that the cultured epithelial autograft may have an
      influence on the quality of scarring.

PMID- 8884007
TI  - Changes in substance P in the jejuna of rats after burns.
AB  - Radioimmunoassay (RIA) was used to determine the dynamic changes of
      immunoreactive substance P (iSP) in the jejuna of rats (TBSA 30 per cent full
      skin thickness burn) during the first 72 h postburn. Immunohistochemistry and
      image analysis techniques were used to observe and quantitate the SP
      immunoreactivity (SP-IR) of positive nerve fibres in the villi of jejuna
      postburn. Changes in the amount of iSP in jejuna of burned rats were: (1) iSP
      increased significantly at 1 h postburn, and the high level of iSP lasted 4 h; it
      then decreased greatly 8 h later with the low level of iSP persisting for 72 h.
      (2) Significant changes in SP-IR-positive nerve fibres in the villi after burn
      were shown by the immunohistochemical studies including the morphoses; the
      distributive densities and SP-IR-positive products in the SP-IR-positive nerve
      fibres. The results quantified by image analysis showed similar alterations in
      the distributive densities and SP-IR-positive products in the nerve fibres in the
      villi during 72 h postburn; which were distinctly elevated by 1 hr then dropped
      by 8 h and 12 h and finally elevated again. The results indicated that the
      irritation-release and consumption of SP occurred in jejuna of rats after burns.
      It might be that SP contributed to the postburn intestinal lesion in rats by
      bioactivities, such as enhancing the vascular permeability and regulating the
      intestinal movement. The SP peptidergic nerve fibres of the villus had a direct
      effect on the damage to mucosal epithelia.

PMID- 8884008
TI  - Hyperbaric oxygen therapy and piracetam decrease the early extension of deep
      partial-thickness burns.
AB  - During the first 24 h, a progression of the burn wound in histological depth or
      extension is often noted. This can only partially be prevented by the routinely
      used protocols of fluid resuscitation and burn wound dressing. In a rat model of
      5% TBSA burn, hyperbaric oxygen therapy (HBOT) and piracetam were evaluated for
      their ability to further prevent this early deepening of the burn wound. After
      infliction of the burn wound, the animals were treated with an accepted basic
      burn wound treatment consisting of mafenide 10% solution humid dressings. They
      were then randomized into three groups: a control group (n = 10), receiving no
      other treatment, a HBOT group (n = 17), receiving 60 min of HBOT (203 kPa) twice
      daily, and a piracetam group (n = 19), receiving piracetam (200 mg/kg IM) twice
      daily. On the third day of treatment, the entire burn wound was exised and
      examined histologically. It was found that both HBOT and piracetam had
      statistically significant effects on the preservation of epidermal basal membrane
      (P < 0.001 and P < 0.01, respectively). HBOT, but not piracetam, further had
      significant effects on the destruction of skin appendages (P < or = 0.05 and P >
      0.05, respectively) and on the degree of subepidermal inflammation, as measured
      by leucocyte infiltration (P < 0.001 and P > 0.05, respectively). Furthermore,
      the HBOT group showed significantly less leucocyte infiltration than the
      piracetam group (P < 0.01). It was concluded that, although the clinical
      importance of the small effects on skin appendage and basal membrane preservation
      may be questionable, the effect on subepidermal leucocyte infiltration is
      striking and warrants further investigation of the anti-inflammatory effects of
      HBOT and possibly piracetam.

PMID- 8884009
TI  - Free tissue transfer in the management of burns.
AB  - Although the majority of burn wounds undergoing surgical treatment require only
      excision with split-skin grafting, the introduction of free microvascular tissue
      transfer has allowed for the preservation of otherwise unsalvageable deep burn
      injuries and the resurfacing of burn scars in areas with no available local
      tissue. A total of 1699 patients with burn injuries were admitted to the Burns
      Unit in Newcastle upon Tyne in the 5 years 1989-1993. During this period 604
      patients (35.5 per cent) required surgical treatment of their burns. Of these
      patients 582 (96.4 per cent) underwent excision of their burns with split-skin
      grafting, 13 (2.1 per cent) of the patients required local flap cover and nine
      patients (1.5 per cent) had free tissue transfer. Free flap loss in this study
      was 22 per cent in burns patients as compared to only 3 per cent in patients
      undergoing microsurgical reconstruction for other reasons.

PMID- 8884010
TI  - Postburn scar carcinomas in Kashmiris.
AB  - Seventy-two Kashmiri patients with postburn scar carcinomas seen over a period of
      12 years have been reviewed. The incidence of this cancer in the valley appears
      to be comparatively high (10.4 percent of squamous cell cancers and 7.6 percent
      of all cutaneous cancers). A Kangri burn was the commonest aetiological agent
      (44.4 percent). The mean age at presentation was 41.5 years, with a mean latent
      period of 35.4 years. None of the patients had metastases and all tumours were
      well differentiated squamous cell carcinomas. Sixty-four patients underwent
      excisional surgery and six had amputations, with a 5-year survival rate of 68.7
      percent, which is better than reported by many other series.

PMID- 8884011
TI  - A comparison of Sil-K and Epiderm in scar management.
AB  - Twenty-six patients with a total of 45 scars were studied to determine the
      efficacy of the new silicone sheet, Sil-K, in treating hypertrophic scars. Twenty
      eight scars were treated with Sil-K and 17 scars were treated with the
      conventional gel, Epiderm. Evaluation based on the scar's colour, texture,
      thickness and regularity was done on a monthly interval for 6 months. Preliminary
      results suggest that both Sil-K and Epiderm are effective in treating
      hypertrophic scars. All of the four parameters studied showed improvement, with
      colour, texture and regularity showing higher percentage of improvement than
      thickness (90, 90, 80 and 50 per cent respectively). Complications such as
      rashes, pruitus, maceration and dry skin were reported by some subjects. Epiderm
      and Sil-K were also compared across factors such as cost, durability, conformity
      and hygiene to assist therapists in choosing the suitable silicone sheet for each
      individual patient.

PMID- 8884012
TI  - Staples and gamgee for securing large-area burns dressings.
AB  - Securing large area burns dressings can be troublesome and time-consuming.
      Circumferentially applying gamgee and stapling it to itself was discovered to be
      easily done, very secure and also had a notably tidy appearance.

PMID- 8884013
TI  - Honey dressing versus boiled potato peel in the treatment of burns: a prospective
      randomized study.
AB  - Honey dressing was compared with boiled potato peel dressings as a cover for
      fresh partial-thickness burns in two groups of 50 randomly allocated patients. In
      the 50 patients treated with honey, 90 per cent of wounds were rendered sterile
      within 7 days. In the 50 patients treated with boiled potato peel dressings,
      persistent infection was noted within 7 days. Of the wounds treated with honey,
      100 per cent healed within 15 days as against 50 per cent in the wounds treated
      with boiled potato peel dressings (mean 10.4 vs. 16.2 days).

PMID- 8884014
TI  - Malignant schwannoma in a burn scar.
AB  - The malignant potential of a burn scar is well recognized. Epidermal malignancies
      predominate and sarcomas are a rare finding. The first case of a malignant
      schwannoma developing in a burn scar is reported, and the management discussed.

PMID- 8884015
TI  - A rare case of burn scar malignancy.
AB  - Malignant changes in burn scars have long been reported in the literature. Most
      cases are squamous cell carcinomas and some other epithelial cell carcinomas.
      Soft tissue tumours are considered rare. A rare case of sarcoma arising in a scar
      on the sole of the foot in a 64-year-old male is reported. He had suffered fire
      burns 25 years previously. Histological findings indicated that the tumour was a
      pleomorphic liposarcoma. Amputation was performed, but he died 3 months after the
      operation. To our knowledge, this is only the second case of liposarcoma
      developing in a burn scar.

PMID- 8884016
TI  - Manifestation of multifocal heterotopic ossifications with unusual locations as a
      complication after severe burn injury.
AB  - Heterotopic bone formation is a well-known but rare complication after burns and
      other traumatic injuries. Pathology, aetiology, progression and management remain
      controversial. Joint immobilization in concert with an altered metabolism and
      aggressive physical therapy are suspected to be the cause of heterotopic bone
      formation. The most frequent sites of manifestation are major joints and large
      muscle groups. The formation of disseminated large ossifications in soft-tissue
      and juxta-articular bone bridges of small joints is barely mentioned in the
      literature. A case of most unusual, massive heterotopic bone formation as a
      complication after severe burn is presented. In this patient serious
      complications after the severe burn injury primarily attracted clinical
      attention, so that diagnostic measures were delayed. Four months later after
      successful weaning from ventilation, the patient could describe his sites of
      pain. The therapeutic options were limited because of extensive and unusual
      localizations. This case emphasizes the necessity of an early and specific
      radiological diagnosis in long-term ventilated patients to avoid this serious
      complication.

PMID- 8884017
TI  - Petrol-related burns.

PMID- 8884019
TI  - Recent references.

PMID- 8884018
TI  - Silicone net and Hypafix as a dressing for skin grafts.

PMID- 8884020
TI  - Pharmacology of pertussis toxin B-oligomer.
AB  - Pertussis toxin (PTX) is a heterohexameric protein, which is divided into
      subunits A and B. The A-subunit (protomer) possesses adenine diphosphate (ADP)
      ribosyltransferase activity, and the B-oligomer confers cell surface binding
      specificity on the toxin. By virtue of the ADP-ribosylation activity in the A
      subunit, PTX has become a very useful pharmacological tool for the identification
      of inhibitory guanine nucleotide binding (Gi) proteins in the plasma membrane.
      However, the pharmacological properties of the PTX B-oligomer are largely
      unknown. In the course of identifying its binding site(s), PTX B-oligomer was
      recently found to elicit direct cellular responses in a variety of cell types.
      Several cell surface receptors with oligosaccharide side chains have been shown
      to be specifically bound by PTX B-oligomer. Moreover, occupation of these
      putative receptors by the B-oligomer alone can trigger phospholipase C and
      tyrosine kinase dependent signal transduction events. The impact of these B
      oligomer-mediated rapid signaling responses on the subsequent ADP-ribosylation of
      Gi protein by the A-subunit remains to be determined. These recent findings
      caution investigators not to attribute inhibitory effects of PTX solely to ADP
      ribosylation of Gi protein without first examining the cellular responses using
      PTX B-oligomer.

PMID- 8884021
TI  - Chemical carcinogenesis, mutagenesis, and teratogenesis.
AB  - An international symposium entitled Chemical Carcinogenesis, Mutagenesis and
      Teratogenesis: a Tribute to James and Elizabeth Miller was held in Toronto, Ont.,
      July 19, 1994. This symposium theme was discussed in the presence of James
      Miller, 79 years young, who with his wife, Elizabeth Miller (1920-1987), are
      considered to be the pioneers of this medical and environmental toxicology
      research field. It is generally believed that the susceptibility of an individual
      to chemical carcinogenesis or teratogenesis varies considerably depending upon
      their genetic makeup, diet, lifestyle, and their environmental exposure. One goal
      of the research discussed at this symposium was an examination of the role of the
      enzymes involved in the metabolic activation and detoxification of carcinogens
      and teratogens. The interindividual variabilities in the levels and activity of
      these enzymes could contribute to the susceptibility of the individual to
      chemical carcinogens or teratogens. At the symposium evidence was presented
      indicating that theta-class glutathione (GSH) S-transferase levels activate
      dihalomethanes and could therefore initiate the carcinogenic response to
      butadiene and 1,2-dibromo-3-chloropropane. The dramatic genetic polymorphism of
      this class of GSH S-transferase could thereby contribute to the individual's
      susceptibility to these carcinogens. Similarly, the GSH S-transferase and GSH
      levels in the embryo and yolk sac that are determined during organogenesis could
      also be important factors in determining the susceptibility of the embryo to
      teratogens. The levels of cytochrome P450 1A2, aromatic amine N
      acetyltransferases, and sulfotransferases could also determine the susceptibility
      of the individual to carcinogenic arylamines. Accordingly, an Ames tester strain
      was described that was genetically engineered so as to express both aromatic
      amine N-acetyltransferase and human cytochrome P450 1A2. This should prove useful
      for predicting which arylamines are likely to be carcinogenic to humans.
      Nonsteroidal anti-inflammatory drugs may also prove useful in inhibiting the
      cytochrome P450s that activate the nitrosamines found in tobacco smoke suspected
      to cause lung cancer. Finally, the sulfotransferase isoforms involved in the
      metabolic activation of carcinogenic arylamines were identified.

PMID- 8884022
TI  - Hemodynamic responses to Pasteurella haemolytica inoculation in calves given type
      2 serotonergic antagonist.
AB  - The effects of saline (control, group C) and metrenperone (treated, group M) on
      systemic and pulmonary hemodynamics were determined in conscious 7- to 15-day-old
      calves after they were intratracheally inoculated with Pasteurella haemolytica.
      Metrenperone, a specific serotonin (5-hydroxytryptamine) receptor antagonist, was
      injected intramuscularly (100 micrograms.kg-1) 2 h after the calves were
      inoculated. Central venous, pulmonary arterial and capillary wedge, and systemic
      arterial pressures were measured, using fluid-filled catheters. Cardiac output
      was measured by the thermodilution technique. Heart rate, stroke volume, and
      pulmonary and systemic vascular resistances were calculated. The parameters were
      measured hourly from the 1st to the 10th h after inoculation. In group C,
      cardiovascular response to P. haemolytica inoculation was marked and typically
      consisted of two systemic hypotensive phases and two pulmonary hypertensive
      phases. The first phase occurred by the 2nd h post inoculation and was induced by
      a transient bradycardia and a systemic vasodilation, leading to profound
      hypotension and reduced venous return. Cardiac performance then transiently
      recovered, but systemic hypotension persisted. The second hypotensive hypodynamic
      phase occurred by the 7th h after inoculation, and was associated with a decline
      in stroke volume, an increase in heart rate, and pulmonary hypertension and
      vasoconstriction. In group M, the early response to P. haemolytica exposure was
      similar to that in controls, indicating that, as in sheep, 5-hydroxytryptamine
      does not contribute to the early hypodynamic response to endotoxemia. In
      contrast, metrenperone completely abolished late increases in pulmonary arterial
      pressure and pulmonary vascular resistance, suggesting that 5-hydroxytryptamine
      contributes to the late pulmonary vasoconstriction. Metrenperone treatment also
      allowed better restoration of heart rate, and hence, cardiac output was
      maintained. In conclusion, 5-hydroxytryptamine might have a role in mediating
      pasteurellic endotoxin induced changes in pulmonary hemodynamics through its type
      2 receptors.

PMID- 8884023
TI  - Quantitation of 6-thioguanine in peripheral blood leukocyte DNA in Crohn's
      disease patients on maintenance 6-mercaptopurine therapy.
AB  - The effects of 6-mercaptopurine (6MP) in inflammatory bowel disease are believed
      to be primarily mediated by its metabolite 6-thioguanine (6TG). Our aim was to
      develop an assay for measuring leukocyte DNA 6TG levels in patients with Crohn's
      disease, and to correlate them with levels of 6TG in erythrocytes. Heparinized
      blood was obtained from 15 adolescent Crohn's disease patients receiving 6MP at
      an average dose of 1.3 mg.kg-1 day-1 (range 0.8-1.6 mg.kg-1 day-1) for a mean of
      23.7 months (range 3-71 months). Leukocyte DNA and erythrocyte 6TG levels were
      measured by an HPLC assay. Leukocyte 6TG levels ranged from 100 to 2305 pmol/mg
      DNA, while erythrocyte 6TG levels ranged from 64 to 1038 pmol/8 x 10(8) red blood
      cells, demonstrating significant interpatient variability. Leukocyte DNA 6TG
      levels correlated directly with erythrocyte 6TG levels, as measured by the
      Spearman rank correlation coefficient (p < 0.05). The HPLC measurement of
      erythrocyte and leukocyte DNA 6TG levels can be useful clinically in monitoring
      compliance, as well as perhaps to tailor drug metabolite levels to achieve the
      desired clinical effect.

PMID- 8884024
TI  - Effects of B1 and B2 kinin receptor antagonists in diabetic mice.
AB  - Streptozotocin (STZ) has been extensively used to produce type I diabetes in
      animals. This experimental disease is characterized by a mild inflammatory
      reaction in the Langerhans islets. Because kinins have been proposed as prominent
      inflammatory mediators in the pathogenesis of several diseases, we decided to
      evaluate the role of kinins and their receptors in the evolution of insulitis.
      Male C57BL/Ks mdb mice were injected with STZ (40 mg/kg) for 5 consecutive days.
      The kinin B1 receptor antagonist [Leu8]des-Arg9-bradykinin or the B2 antagonist d
      Arg[Hyp3,Thi5,D-Tic7, Oic8]bradykinin (HOE-140) was injected subcutaneously into
      STZ mice at 300 micrograms/kg body weight twice a day and 500 micrograms/kg per
      day, respectively. Treatment with antagonists was started 3 days after STZ and
      lasted for 10 days. Plasma glucose was determined by the glucose oxidase method,
      and urine samples collected on day 13 were assayed for proteins, nitrites, and
      kallikreins. Diabetic mice showed hyperglycemia and increased diuresis, marked
      proteinuria, and increased excretion of nitrites and kallikreins. The treatment
      with the B2 receptor antagonist did not show any effect on glycemia, but it
      significantly reduced water and protein excretion, compared with the STZ group.
      STZ mice treated with the B1 receptor antagonist showed normal glycemia and
      complete normalization of diuresis and protein, nitrite, and kallikrein
      excretion. The results obtained in the present investigation support the
      assumption that the kallikrein-kinin system intervenes in the maintenance of
      diabetic lesions, and they also indicate that B1 kinin receptors play a
      significant role in this experimental disease.

PMID- 8884026
TI  - Adaptive cytoprotection against ethanol-induced small intestinal mucosal injury.
AB  - Exposure of the small intestinal mucose to 6% ethanol (which is found in human
      jejunum during alcohol consumption) causes morphological alterations, and
      increased permeability of the mucosa and histamine release from intestinal mast
      cells. The released histamine is shown to mediate a significant component of the
      increased mucosal permeability (i.e., mucosal injury). In the present study, we
      have investigated whether adaptive cytoprotection occurs against the increased
      mucosal permeability and histamine release induced by 6% ethanol. Rabbits were
      used. In each animal, three adjacent segments of upper small intestine were pre
      perfused for 30 min, and then perfused for 90 min in the following order control
      solution followed by control solution (control segment); control solution
      followed by 6% ethanol (ethanol segment); 1% ethanol followed by 6% ethanol
      (pretreated ethanol segment). During the 90-min perfusion, mucosal permeability
      of each segment was measured by analyzing the effluent for intraluminal clearance
      of i.v. administered 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA)
      and 125I-labelled bovine serum albumin (125I-BSA). Mast cell histamine release
      was assessed by determining histamine concentration of the gut effluent. All
      measurements were higher in the ethanol segments than in the controls. These
      ethanol effects were significantly lower in the pretreated ethanol segments,
      indicating that adaptive cytoprotection occurs against the mucosal injury induced
      by 6% ethanol. These findings are discussed in relation to the literature on
      mucosal effects of intestinal intraluminal ethanol.

PMID- 8884027
TI  - Cardiopulmonary actions of muscarinic receptor subtypes in the newborn dog.
AB  - We addressed the role of muscarinic receptor subtypes in neurally mediated
      bronchoconstriction in vivo and airway smooth muscle contraction in vitro in the
      newborn dog. The in vivo dose-response effects of "selective" muscarinic
      antagonists on changes in lung resistance (RL) and heart rate (HR) in response to
      electrical stimulation of the vagus nerves were obtained in four groups of
      newborns. Each group was exposed to a different muscarinic antagonist: M1
      selective pirenzepine (pir), M2-selective AF-DX 116 (11-[2-[(diethylamino)methyl]
      1-piperidinyl]acetyl-5,11-dihydro-6H-pyrid o- [2,3-b]-[1,4]-benzodiazepine-6
      one), M3-selective p-F-HHSiD (p-fluoro-hexahydro-sila-difenidol), and
      nonselective atropine (atr). In vitro concentration-response effects of pir and
      AF-DX 116 were obtained for neurally induced contractions of tracheal smooth
      muscle, elicited by electrical field stimulation. In a separate series of
      experiments we measured the bronchoconstrictor response to the muscarinic agonist
      acetylcholine delivered by right heart injection. Muscarinic antagonists reduced
      RL and HR responses to vagal stimulation in a dose-dependant fashion; however,
      ED50 values and selectivity for airway and cardiac responses (HR/RL ED50 ratio)
      were significantly different between antagonists. The rank order of potencies for
      inhibition of the increase in RL was atr > pir, M1 > p-F-HHSiD, M3 > AF-DX 116,
      M2, while that for HR was atr > AF-DX 116 > pir > p-F-HHSiD. AF-DX 116
      preferentially inhibited the HR response, as reflected by the lowest HR/RL ED50
      ratio (p < 0.001). The remaining antagonists preferentially inhibited RL, with
      the highest HR/RL ED50 ratio seen for p-F-HHSiD. These data suggest that
      muscarinic receptor subtypes are differentiated at birth and mediate cardiac and
      airway responses to vagal stimulation. We did not find autoinhibitory actions of
      airway M2 receptors on either the in vivo bronchoconstrictor response or the in
      vitro contractile response to electrical field stimulation. This suggests that
      neonatal airway M2 receptors, but not myocardial M2 receptors, are reduced in
      number or weakly coupled to muscarinic signal transduction mechanisms. Direct
      activation of airway smooth muscle by acetylcholine caused dose-dependent
      increases in RL that reached a plateau at approximately 200% at 100 micrograms,
      similar to values reported for vagal stimulation.

PMID- 8884025
TI  - Synergism between prostaglandin E2 and isoproterenol in stimulating glucose
      oxidation in the heart.
AB  - The increase in cardiac contractile function following adrenergic stimulation is
      accompanied by increased glucose metabolism. Since prostaglandin E2 (PGE2) can
      internalize beta-receptors, we determined what effects PGE2 and isoproterenol
      have on glycolysis and glucose oxidation in the isolated working rat heart. All
      hearts were perfused with Krebs-Henseleit buffer containing 11 mM [5-3H,
      14C(U)]glucose, 100 microU/mL insulin, and 3% albumin. In the presence of 0.4 mM
      palmitate and 1.25 mM free Ca2+, isoproterenol (3 x 10(-8) M) increased the heart
      rate x peak systolic pressure product from 27 +/- 1 to 43 +/- 1 mmHg.beats.min
      1.10(3) (1 mmHg = 133.3 Pa). This was accompanied by an increase in glycolytic
      rates from 3564 +/- 231 to 7775 +/- 475 nmol.g-1 dry weight min-1 and an increase
      in glucose oxidation from 930 +/- 72 to 2591 +/- 239 nmol.g-1 dry weight.min-1.
      Addition of PGE2 (10(-9) M) did not affect the isoproterenol stimulation of
      glycolysis, but caused a further increase in glucose oxidation (to 3863 +/- 495
      nmol.g-1 dry weight.min-1). In the absence of isoproterenol, 10(-9) M PGE2 had no
      effect on either glycolysis or glucose oxidation. When perfusate [Ca2+] was
      raised to 2.5 mM, a significant increase in glycolysis was seen in control hearts
      (from 3564 +/- 231 to 5679 +/- 374 nmol.g-1 dry weight.min-1). The effects of
      isoproterenol and PGE2 on glucose metabolism remained, although the synergistic
      effects of PGE2 on glucose oxidation were less dramatic. When 1.2 mM palmitate
      was present in hearts perfused with 2.5 mM Ca2+, a decrease was seen in both
      glycolysis (from 5679 +/- 374 to 3027 +/- 346 nmol.g-1 dry weight.min-1) and
      glucose oxidation (from 1056 +/- 170 to 221 +/- 29 nmol.g-1 dry weight.min-1).
      Even at this high concentration of fatty acid, isoproterenol stimulated glucose
      oxidation (from 221 +/- 29 to 859 +/- 69 nmol.g-1 dry weight min-1), and addition
      of PGE2 resulted in a significant further increase (1021 +/- 139 nmol.g-1 dry
      weight.min-1). These data demonstrate that concentrations of PGE2 that bind to
      the high affinity cardiac PGE2 receptor have no effect on glucose metabolism in
      the absence of beta-agonists. In the presence of isoproterenol, which
      dramatically stimulates both glycolysis and glucose oxidation, PGE2 has a
      synergistic effect on glucose oxidation at lower fatty acid concentrations. These
      findings suggest that PGE2 receptors in the heart function to potentiate rather
      than decrease beta-adrenergic stimulation of glucose metabolism.

PMID- 8884028
TI  - Renal nerves do not modulate the renal and endocrine responses to furosemide in
      conscious lambs.
AB  - To test the hypothesis that renal sympathetic nerves influence the renal and
      renin responses to furosemide in conscious newborn animals, experiments were
      carried out in chronically instrumented lambs with either bilateral renal
      denervation (denervated, n = 7, age = 13 +/- 3 (SD) days) or intact renal
      sympathetic nerves (intact, n = 6, age = 13 +/- 4 (SD) days), at least 4 days
      after surgery. Basal glomerular filtration rate (GFR), urinary flow, and sodium
      excretion rates were similar in intact and denervated lambs (p > 0.5). A prompt
      diuretic and natriuretic response and a decrease in GFR occurred after i.v.
      furosemide (2 mg/kg); these responses were similar in intact and denervated
      lambs. Basal plasma renin activity (PRA) was not altered by renal denervation.
      PRA increased 10 min after furosemide (p < 0.001) and remained elevated at 90
      min; the response was similar in both groups of lambs. Basal plasma aldosterone
      levels were elevated in denervated (191 +/- 232 (SD) pg/mL) compared with intact
      lambs (62 +/- 24 (SD) pg/mL). Plasma aldosterone levels increased after
      furosemide administration in both groups of animals. These data provide evidence
      to suggest that renal sympathetic nerves do not appear to modulate the renal and
      endocrine responses to furosemide, at least at a dose of 2 mg/kg. Our
      observations also support the premise that early in life, aldosterone counteracts
      the effects of renal denervation on fluid and electrolyte homeostasis.

PMID- 8884029
TI  - Marital therapy.

PMID- 8884030
TI  - A critical review of marital therapy outcome research.
AB  - OBJECTIVE: This review critically examines conceptual and methodological issues
      of outcome research designed to evaluate the efficacy of marital therapy (MT).
      Behavioural marital therapy (BMT), cognitively orientated marital therapy (COMT),
      emotionally focused marital therapy (EFMT), and insight-oriented marital therapy
      (IOMT) have provided evidence for efficacy. METHOD: The initial literature search
      involved the use of the MEDLINE and Psychlit CD-ROM data bases. A secondary
      literature search based on citations in articles discovered in the initial search
      was also conducted. Three broad categories involving the delineation of the
      client sample, study design considerations, and determination of treatment
      effects were addressed to investigate the quality of evidence concerning the
      efficacy of MT. RESULTS: None of the 4 approaches has proven superiority in
      efficacy, and the research does not provide evidence for the superiority of any
      one approach in distinct types of marital discord. There is some evidence to
      indicate that future outcome research should avoid the use of "waiting list
      control groups," since their use appears to be neither ethical nor humane in
      marital discord research. CONCLUSIONS: The authors suggest that the concept of
      treatment efficiency may be more clinically relevant to outcome research. A gold
      standard for "efficiency" would suggest that a marital therapy approach should
      produce subjective and objective improvement in 50% of eligible couples, and this
      improvement should be maintained in half of these couples at the one-year follow
      up assessment. This standard would be comparable to the data on the 4 effective
      approaches described in this review.

PMID- 8884031
TI  - Posttraumatic stress disorder and motor vehicle accidents: a multidisciplinary
      overview.
AB  - OBJECTIVE: Motor vehicle accidents (MVA) may result in intractable disability.
      This paper investigates posttraumatic stress disorder (PTSD) as a potential
      cause. METHOD: The literature was reviewed for recent studies on prevalence,
      symptom profile, and outcome of PTSD. RESULTS: PTSD is prevalent in roughly 10%
      of survivors of MVAs during the first year. Comorbid depression and pain are
      common. Medical complications, psychophysiological reactivity, and possibly
      litigation may slow remission. Phobic symptoms can persist for years. Mood
      disturbance may augment the impact of pain on daily living and on self-perceived
      disability. CONCLUSION: Recently developed screening instrument, structured
      interviews, and behavioural approach tests yield quantitative and reliable
      assessments of symptom severity. Cognitive-behavioural intervention and
      antidepressants may improve coping, ease fear, and reduce the impact of pain.

PMID- 8884032
TI  - An examination of the relationship of homelessness to mental disorder, criminal
      behaviour, and health care in a pretrial jail population.
AB  - OBJECTIVE: To examine the prevalence of homelessness and its relationship to
      mental disorder, criminal behaviour, and health care. METHOD: Interview and file
      data were collected for 790 male admissions to a large, pretrial jail facility
      over a 12-month period. RESULTS: A significant relationship was found between
      homelessness and severe mental disorder as well as between homelessness and prior
      psychiatric history. There were no significant differences found between the
      homeless and the nonhomeless on the types of crimes for which they were
      incarcerated or on contact with health care services within the past year.
      CONCLUSION: The findings indicate the need for a link between the jail and
      community services for homeless individuals.

PMID- 8884033
TI  - Psychiatric manifestations of multiple sclerosis: a review.
AB  - OBJECTIVE: To report the occurrence, type, causes, and management of psychiatric
      manifestations in multiple sclerosis (MS). METHOD: Review of recent, relevant
      literature. RESULTS: Psychiatric illness, especially depression, occurs much more
      frequently than expected in patients with MS, is frequently unrecognized or
      ignored, and is treatable using standard methods, although patients with MS may
      be unusually sensitive to side effects of tricyclic antidepressants. CONCLUSIONS:
      Research is needed to better define the causes of psychiatric syndromes in
      patients with MS. Those treating MS should increase their awareness of and
      sensitivity to the likelihood of psychiatric disorder in these patients.

PMID- 8884034
TI  - Neonatal insult to the hippocampal region and schizophrenia: a review and a
      putative animal model.
AB  - OBJECTIVE: To review the mounting evidence implicating early hippocampal
      dysfunction in the pathogenesis and the pathophysiology of schizophrenia. An
      account is made of recent neurodevelopmental hypotheses indicating how an early
      dysfunction of the hippocampal region disrupts maturational events in brain
      systems connected to that structure, thus inducing dysfunctional connectional
      development. Finally, an animal model is presented. METHOD: Socioemotional
      behaviour of monkeys (Macaca mulatta) with selective neonatal hippocampal lesions
      was assessed by analyzing their interactions with their age-matched controls at 2
      months, 6 months, and 5 to 8 years of age and by comparing the social
      interactions at each age with those of normal controls paired together. RESULTS:
      At 2 months of age, monkeys with neonatal hippocampal lesions presented minor
      disturbances in initiation of social interactions. These subtle changes of
      behaviour were less evident at 6 months, although by that age, the operated
      monkeys displayed more withdrawals in response to an increase in aggressive
      responses from their unoperated peers. In adulthood, the amount of time spent by
      the hippocampectomized monkeys in social contacts with their normal peers
      decreased markedly. In addition, operated monkeys exhibited more locomotor
      stereotypies than normal controls. CONCLUSION: These experimental findings
      indicate that the time-course and nature of the behavioural disturbances
      resulting from early trauma to the hippocampal region have some similarities with
      the clinical symptoms of schizophrenic patients and the typical time-course of
      the disease.

PMID- 8884035
TI  - Psychotropic medication and insomnia complaints in two epidemiological studies.
AB  - OBJECTIVE: This study compared prescribed psychotropic medication patterns for
      reported sleep disorders in French and Quebec samples. METHOD: The first study
      was undertaken in France (N = 5622) and the second in the metropolitan area of
      Montreal (N = 1722). Lay interviewers used a specialized knowledge-based system
      for the purpose of evaluating sleep disorders by telephone. RESULTS: Results
      showed similar prevalence of insomnia complaints in both samples (20.1% and
      17.8%, respectively). A higher level of psychotropic consumption was found in
      France (11.7% [95% confidence interval (CI), 10.9 to 12.5]) compared with Quebec,
      however, where consumption was less than half the French rate (5.5% [95% CI, 4.4
      to 6.6]). Both studies identified females and the elderly as the primary
      consumers of these drugs. For approximately two-thirds of both samples, sleep
      promoting medications were prescribed for a year or longer, revealing a
      chronicity of the consumption. Approximately 4 out of 5 prescriptions for
      sleeping medications were ordered by general practitioners in both samples.
      CONCLUSION: These findings clearly show a higher prevalence of psychotropic drug
      use in the French compared with the Quebec population. The patterns of
      consumption and prescription, however, are quite similar in both studies.

PMID- 8884036
TI  - Serum cholesterol levels in patients with generalized anxiety disorder (GAD) and
      with GAD and comorbid major depression.
AB  - OBJECTIVE: To investigate risk for cardiovascular disease in patients with GAD,
      as well as the effects of comorbid major depression (MD). METHOD: Predrug-trial
      serum cholesterol and triglyceride levels were assessed in 38 patients with pure
      GAD and compared with those of 21 patients with mixed GAD and comorbid (MD).
      RESULTS: Significantly higher cholesterol and triglyceride levels were found in
      the GAD group. CONCLUSION: Increased noradrenergic activity may be responsible
      for elevations in lipid levels in patients with pure GAD.

PMID- 8884037
TI  - Case-control studies of cardiovascular medications as risk factors for clinically
      diagnosed depressive disorders in a hospitalized population.
AB  - OBJECTIVE: Certain medications used in cardiovascular therapeutics may contribute
      to the etiology of substance-induced mood disorders. These medications include
      digoxin, angiotensin converting enzyme (ACE) inhibitors, beta-blockers, and
      calcium channel blockers. The objective of this study was to evaluate
      associations between these drugs and clinical diagnoses of depressive disorders
      in a population of hospitalized patients. METHOD: Two case-control studies were
      conducted. For each study, subjects were selected from a health records data base
      maintained at the Calgary General Hospital. Selection of subjects in the first
      study was restricted to those receiving a discharge diagnosis of congestive heart
      failure and in the second study to subjects receiving a discharge diagnosis of
      hypertension. In each of these 2 studies, a single case group was selected along
      with 2 control groups: a psychiatric control group consisting of subjects
      receiving a psychiatric diagnosis other than a depressive disorder and a
      nonpsychiatric control group receiving no psychiatric diagnoses. Drug exposures
      and other variables were recorded from a chart review. RESULTS: Exposures to
      digoxin, beta-blockers, and calcium channel blockers were not associated with
      depressive diagnoses. An association was observed, however, for ACE inhibitors.
      An elevated odds ratio (OR) was observed in each case-control study and was
      stronger in female subjects and subjects over the age of 65. CONCLUSIONS: This is
      the first reported epidemiological evidence of an association between ACE
      inhibitors and depressive disorders. The design of this study does not permit a
      determination of whether the observed association was causal. Additional studies
      are needed.

PMID- 8884038
TI  - Re: Psychiatric practice for the coming decade.

PMID- 8884039
TI  - Re: Impulsivity, defensive functioning, and borderline personality disorder.

PMID- 8884040
TI  - Re: clozapine--current status and role in the pharmacotherapy of schizophrenia.

PMID- 8884041
TI  - Bromocriptine as adjunctive therapy to clozapine in treatment-resistant
      schizophrenia.

PMID- 8884042
TI  - Swelling of salivary glands with clozapine treatment.

PMID- 8884043
TI  - Occult multiple sclerosis presenting with psychosis.

PMID- 8884044
TI  - Venlafaxine withdrawal symptoms.

PMID- 8884045
TI  - Memory and clinical psychiatry.

PMID- 8884046
TI  - Is cognitive psychopathology plausible? Illustrations from memory research.
AB  - OBJECTIVE: To examine the strengths and weaknesses of cognitive psychopathology
      through the specific examples of the memory impairments associated with the
      administration of benzodiazepines, with schizophrenia, and with depression.
      METHOD: These examples are analyzed with reference to a model of memory based on
      the principle of division between specialized and central processing structures.
      A basic contention is that it is useful to consider 2 broad classes of processes
      automatic, associative, or sensory/perceptual processes on the one hand and
      intentional, strategic, or reflective processes on the other hand-as being
      separate. RESULTS: The functional mechanisms of the memory impairments associated
      with these conditions are beginning to be identified, and there is preliminary
      evidence that a deficit in an elementary computation may have dramatic
      consequences on highest cognitive functions. There is also evidence that certain
      memory impairments are linked to specific dysfunctional outcomes in everyday
      life. By showing that specific rate-limiting factors of cognitive performance can
      be identified and are amenable to cognitive interventions, existing data open the
      door for theoretically and empirically based cognitive remediation of mental
      disorders. CONCLUSION: The bulk of available evidence (albeit limited) makes the
      enterprise of cognitive psychopathology quite plausible and convincing.

PMID- 8884047
TI  - The heterogeneity of memory dysfunction in schizophrenia.
AB  - OBJECTIVE: To characterize the memory dysfunction of schizophrenic patients.
      METHOD: The components of the human memory system are described, and then a
      review of the various memory deficits identified among patients suffering from
      schizophrenia is presented. Finally, an overview of the latest developments in
      the comprehension of schizophrenia and a discussion on certain proposals advanced
      by various researchers in the field intended to shed light on the disorder is
      provided. RESULTS: Schizophrenia appears to be an amalgamation of many different
      disorders. No single model for identifying the disorder has been able to
      encompass every aspect of schizophrenia. CONCLUSION: Future studies will need to
      consider new ways of selecting and grouping schizophrenic patients.

PMID- 8884048
TI  - Differential effects of D2- and D4-blocking neuroleptics on the procedural
      learning of schizophrenic patients.
AB  - OBJECTIVE: To illustrate the differential effects of D2- and D4-blocking
      neuroleptics on the procedural learning of patients with schizophrenia. METHOD:
      Twenty-nine schizophrenic patients were divided into 3 groups according to their
      pharmacological treatment: 1) drug naive, 2) haloperidol, and 3) clozapine. They
      were all assessed on clinical and procedural measures, the latter being the
      mirror drawing task. RESULTS: All groups showed progressive learning over the
      successive trials, and drug-naive patients performed better than the other
      groups. Patients in the haloperidol group showed many fluctuations over trials,
      suggesting difficulty in the progressive automation of the task. Such
      fluctuations did not occur in the clozapine group, but performances per se were
      worse than in the other groups during the learning trials. Automation of the task
      occurred at the same point (second block of trials) for all groups. CONCLUSION:
      These results suggest that D2- and D4-blocking neuroleptics do not similarly
      affect striatal dependent procedural learning in schizophrenia.

PMID- 8884049
TI  - The incidence of cancer in the Czech Republic from 1973 to 1989: cancers with non
      parallel trends in age groups.
AB  - A detailed analysis was made of the malignant cancer incidence rates for the
      Czech Republic for 1973-1989, concentrating on time trends in five-year age
      groups. The results were compared with the trend of age-standardized incidence
      (Standardized Incidence Ratio, SIR) for each cancer type. The dynamics of the
      changes in the incidence of each type of cancer often proved to be different for
      various age groups and in some cases even opposite trends were identified: Lung
      cancer in men-the SIR trend is insignificant, in the 45 to 64 years age groups an
      increase in incidence, in the 70 to 79 years age groups a decrease; testicular
      cancer-the SIR trend is growing, in the 20 to 44 years age groups the increase is
      up to 2.5 times higher in comparison with the SIR trend, in the 60 to 74 years
      group a decrease; cervical cancer-the SIR trend is insignificant, in the 30 to 39
      years age groups an increase, in the 45 to 49 years groups a decrease; Hodgkin's
      disease-the SIR trend is insignificant for women, a slight decrease for men, in
      both sexes a rise in the 15 to 19 years age group, a drop in the 50 to 54 years
      age group. All identified cases of striking non-parallel trends in age groups
      have to be regarded as very displeasing as they present "a shift to the left",
      i.e. a redistribution of the occurrence of the illness towards younger age
      groups. The causes of this phenomenon are not entirely clear, however, the
      results achieved demonstrate the necessity of further evaluation of
      oncological/epidemiological data in narrow age groups.

PMID- 8884050
TI  - The effect of cigarettes smoking on the blood counts of T and NK cells in
      subjects with occupational exposure to organic solvents.
AB  - The study was carried out in a population of 139 men, divided into two control
      groups: 40 non-smokers and 39 smokers not exposed to chemical compounds, and two
      groups exposed to them: 19 non-smokers and 41 cigarette smokers with occupational
      contact with organic solvents. The results of toxicological analyses of air and
      chromatographic analyses of solvents demonstrated the presence of benzene,
      toluene, xylene and their partly hydrogenated derivatives, paraffin hydrocarbons,
      oleins, naphthenes (components of painter's naphtha), monohydric and polyhydric
      alcohols (butanol, cyclohexanol, butylene glycol) esters (ethyleneglycol acetate,
      butyl acetate) and ketones (methylisobutyl ketone, cyclohexanone). In the time of
      the studies the TWA values for benzene were 0 to 38 mg x m-3 (0 to 12 ppm), with
      arithmetic mean averages of about 19 mg x m-3 (6 ppm) and for the level of
      benzene 0-351 mg x m-3 (0-110 ppm) with arithmetic mean annual averages of about
      48 mg x m-3 (15 ppm). Mean phenol concentration in the urine of the workers in
      groups I, II, III and IV respectively was: 7.9 +/- 3.5; 10.0 +/- 5.8; 16.8 +/-
      6.2 and 18.4 +/- 9.7 mg x l-1. Hippuric acid concentration in the urine of the
      workers in groups I to IV was: 496 +/- 326, 538 +/- 341, 982 +/- 420 and 1107 +/-
      507 mg x l-1 respectively. The absolute counts were determined of T-cells (CD
      3+), T-helper (CD 4+), T-suppressor (CD 8+) cells and natural killer (NK) cells
      (CD 16+) in the peripheral blood by indirect immunofluorescence. In the subjects
      with occupational exposure to organic solvents the counts of T-cells and NK-cells
      were reduced, and the number of T-suppressor cells was raised which resulted in a
      decrease of the T-helper/T-suppressor ratio. These changes were more pronounced
      in cigarette smokers. The assessment of the immunotoxic effect of organic
      solvents during occupational exposure should take into consideration the
      possibility of a synergistic action with tobacco and may be of practical use for
      monitoring the toxic effect of organic solvents on the lymphocyte system.

PMID- 8884051
TI  - New serotype candidate of Neisseria meningitidis.
AB  - In spite of a large collection of MAbs used for the whole-cell ELISA (WCE) in the
      National Reference Laboratory for Meningococcal Infections in Prague 50-80% of
      N.meningitidis strains isolated in the Czech Republic remained non-typable (NT)
      and/or non-subtypable (NST). A project focused on the problem of NT/NST
      N.meningitidis was started and the new serotype candidate designated "22"
      resulted from this research. This paper presents the method of preparing and
      testing of the monoclonal antibody (MAb) specific for this new serotype and the
      first experience acquired from using it. The new serotype-specific MAb is of IgG3
      class, does not react with any serotype/subtype reference strains and reacts in
      WCE with the strain used for its production and with some other NT/NST strains in
      the dilution 1:1,000. A collection of 97 N.meningitidis B:NT strains isolated
      from cerebrospinal fluid and/or blood of patients with invasive disease in the
      Czech Republic since 1973 to 1995 was serotyped using the new serotype "22"
      specific MAb and 37 of these strains (38.2%) gave positive WCE result. The total
      number of 59 N.meningitidis B:NT strains isolated in 1995 from various clinical
      situations were serotyped and 26 of them (44.1%) were positive with the new
      serotype "22"-specific MAb. Seven of these N.meningitidis B:NT strains isolated
      in 1995 from various clinical situations were serotyped and 26 of them (44.1%)
      were positive with the new serotype "22"-specific MAb. Seven of these
      N.meningitidis B: "22" strains were isolated from cerebrospinal fluid or blood of
      patients with invasive meningococcal disease and prevailed in the age group of 0
      4 years (5 cases). The significance of the new serotype candidate was underlined
      recently, when this serotype "22" was recognized in N.meningitidis B strain
      isolated from a died 10 months old boy. These results indicate the
      epidemiological and clinical significance of the new serotype candidate "22" in
      the Czech Republic.

PMID- 8884052
TI  - Assessment of the discomfort threshold of command board operators in automated
      productions with respect to its application in professional selection.
AB  - The discomfort threshold problem is not yet clear from the audiological point of
      view. Its significance for work physiology and hygiene is not enough clarified.
      This paper discussed the results of a study of the discomfort threshold,
      performed including 385 operators from the State Company "Kremikovtzi", divided
      into 4 groups (3 groups according to length of service and one control group).
      The most prominent changes were found in operators with increased tonal auditory
      threshold up to 45 and over 50 dB with high confidential probability. The
      observed changes are distributed in 3 groups: 1. increased tonal auditory
      threshold (up to 30 dB) without decrease of the discomfort threshold; 2.
      decreased discomfort threshold (with about 15-20 dB) at increased tonal auditory
      threshold (up to 45 dB); 3. decreased discomfort threshold at increased (over 50
      dB) tonal auditory threshold. The auditory scope of the operators, belonging to
      groups III and IV (with the longest length of service) is narrowed, being
      distorted for the latter. This pathophysiological phenomenon can be explained by
      an enhanced effect of sound irritation and the presence of a recruitment
      phenomenon with possible engagement of the central part of the auditory analyzer.
      It is concluded that the discomfort threshold is a sensitive indicator for the
      state of the individual norms for speech-sound-noise discomfort. The comparison
      of the discomfort threshold with the hygienic standards and the noise levels at
      each particular working place can be used as a criterion for the professional
      selection for work in conditions of masking noise effect and its tolerance with
      respect to achieving the individual discomfort level depending on the intensity
      of the speech-sound-noise signals at a particular working place.

PMID- 8884053
TI  - Prevalence study of serious substance abusers in the Czech Republic.
AB  - In October of 1995, a prevalence study of serious substance abusers was carried
      out in the Czech Republic. The prevalence study focused on: 1. persons
      hospitalized because of drug addiction as of 31.10.1995; 2. persons who visited
      one of the treatment/contact centres during October of 1995. Data on serious
      addictive substance abusers were collected from 142 treatment/contact centres.
      The overall prevalence in the 15-39-year age group is 30.3/100,000 inhabitants,
      the highest in Prague (115.0/100,000 inhabitants), followed by Northern Bohemia
      (34.1) and Northern Moravia (32.0). The most frequently used primary drug remains
      pervitin (349 users, i.e. 35.5%), followed by heroin in the second place (126,
      i.e. 12.9%), marihuana in the third place (94, i.e. 9.4%) and toluene in the
      fourth place (81, 8.1%). The 15-19-year age group is the most affected, and
      corresponds to 36.9% of all users. In this age category, women predominate (47.2%
      of all users). Heroin is equally used in the 15-19-year and 20-24-year age
      groups, while pervitin is used most in the 15-19-year age group, as are marihuana
      and toluene; the frequency of gambling increases more or less with age. Heroin is
      used most in Northern Bohemia (48.4%) and Prague (24.6%), and pervitin in Prague
      (34.7%) and Northern Moravia (18.9%). Data on injection administration of drugs,
      which is dangerous because of the possibility of transmission of hepatitis and
      HIV, confirm that almost two thirds of all users prefer this means of
      application. The great majority of all serious abusers are persons with only
      elementary schooling.

PMID- 8884054
TI  - Male reproductive function in workers exposed to vibration.
AB  - Male infertility is a significant health problem. Increasing attention has been
      paid to the use of semen analysis as an indicator of exposure to potential
      reproductive hazards. The aim of the current paper was to study the effects of
      vibrations on the spermatogenesis in workers of different occupational groups
      (professional drivers, miners, engine drivers, etc.). Semen samples were analyzed
      for pH, volume, turbidity, sperm density sperm count and sperm morphology.
      Workers had an increased prevalence of oligospermia and azoospermia. The semen
      volume and percentage of motile spermatozoa decreased significantly and the
      incidence of sperm malformation increased in exposed workers.

PMID- 8884055
TI  - Bacillary tuberculosis in the Czech Republic: developmental trends in the 1981
      1993 period.
AB  - Results of an automated information system on bacillary tuberculosis and
      mycobacterioses (ISBT) operating in the Czech Republic since 1981 nation-wide
      have been employed in this study. This system collects and processes data
      reported by all mycobacteriology laboratories in the country (34 in 1993) on each
      person disseminating pathogenic and/or opportunistic mycobacteria, on
      pathological materials examined in these patients and on methods applied for
      detection and identification of isolated mycobacteria Results of the 1981-1993
      period were analyzed in this study. The annual incidence of bacillary
      tuberculosis cases identified by culture fell down from 2655 (25.8 per 100,000
      popul.) in 1981 to 1139 (11.0 per 100,000 popul.) in 1993, i.e. by 57.4% in
      total, and by 4.8% in average annually. The decrease of annual mean values
      differed between two periods, from 1981 to 1985 and from 1986 to 1993, being 8.7%
      in the first and 3.7% in the successive period. The incidence of cases detected
      by direct microscopy of sputum showed a decline from 615 to 410 cases (5.97 to
      3.97 per 100,000 popul.) in the 1981 to 1993 period, i.e. 2.8% annually. The
      analysis of the development and of the present state of the bacillary
      tuberculosis is instrumental in estimating the today's burden of the tuberculosis
      problem in the Czech Republic. Although distinct sings of worsened
      epidemiological parameters were not shown in this study, some disturbing findings
      can be considered as alerting: (a) a slowdown of the declining trend of bacillary
      tuberculosis cases detected by culture techniques seen in a few recent years, and
      (b) conserving potential tuberculosis pools in patients suffering from serious
      forms of the disease detectable by direct microscopy.

PMID- 8884056
TI  - Risk factors of intrauterine growth retardation: a study of an urban population
      in Poland.
AB  - The main objective of the study was to examine the role of selected socio
      occupational factors on the development of intrauterine growth retardation (IUGR)
      in the urban population of Lodz, Poland. An epidemiological model of the case
      control study was employed. Both the cases and controls were recruited from the
      female population covered by obstetric services in district hospitals during 1
      January-30 June 1992. A group of cases included 92 females who delivered IUGR
      children, the control group-438 mothers of term born eutrophic babies. The
      presence of the relationship between IUGR manifestation and selected variables
      was initially assessed using the unadjusted odds ratio (OR). The variables
      described as significant were considered in the logistic regressions models,
      separately for all women and those with previous pregnancies. A comparison of the
      groups of cases and controls has revealed a significant excess of risk of
      delivering an IUGR child by mothers with the following characteristics: marital
      status-single, low educational level, low height (less than 1.60 m) low
      prepregnancy weight and low maternal weight gain. An elevated risk of delivering
      an IUGR child was found in the group of women who reported to have their first
      contact with the physician after 12 weeks of pregnancy. An adverse effect of
      prolonged vaginal bleeding was observed. Women who recently lost their job,
      compared to those employed continuously during pregnancy, were at an increased
      risk of IUGR. Cigarette smoking appeared to be the most important variable
      affecting the evaluated pregnancy outcome. For the women smoking 6-10 and more
      than 10 cigarettes a day, the risk of delivering an IUGR child was found to be
      almost 4 and 7 times, respectively, higher than for non-smokers. A logistic
      regression covering all the above mentioned maternal characteristics was
      employed. Only four of them proved to be significant: low maternal weight gain,
      prolonged vaginal bleeding, smoking and the marital status-single. The process of
      preventing IUGR and its consequences requires more effective activities aimed at
      increasing the level of health education and stimulating the development of
      appropriate, health-oriented behaviour.

PMID- 8884057
TI  - Behaviour of Acinetobacter strains with normal human serum.
AB  - The bactericidal activity of normal human serum (NHS) and treated NHS to avoid
      either the classical complement pathway (CPC) or the alternative complement
      pathway (APC) was studied with four strains identified as Acinetobacter baumanii.
      Three of them were sensitive to serum whereas only one was serum resistant. The
      serum sensitive strains showed different susceptibility mechanisms: one strain
      was sensitive to both the CPC and the APC and the others were sensitive only to
      APC. Serum sensitive and serum resistant strains showed on PAGE-SDS and silver
      strain incomplete profiles of lipopolysaccharides (LPS). In all cases the
      carbohydrate percentage of LPS was lower than the value corresponding to
      Salmonella enteritidis with complete profiles of LPS. The strain sensitive to CPC
      and APC had a lower carbohydrate content. The serum sensitivity of the three
      strains could be attributed to the presence of incomplete LPS, while the serum
      resistance could be assigned either to small variations in the LPS composition or
      to some particular membrane component.

PMID- 8884058
TI  - Confronting the prenatal effects of active and passive tobacco smoking on the
      birth weight of children.
AB  - The purpose of the paper is to present the effects of active and passive tobacco
      smoking during pregnancy on the birth weight in the sample of 1165 schoolchildren
      covered by the health survey in Cracow. Data on main-stream tobacco smoke (MS)
      and side-stream tobacco smoke (SS) and the birth weight of children were
      collected by standardized interviews with mothers. As expected, exposure to MS
      tobacco smoke was the single strongest factor related to the reduced birth
      weight, however, the effect was statistically significant only in those
      respondents who confirmed the cigarette smoking over the whole pregnancy period.
      On the basis of multiple regression model considering child's gender, active and
      passive smoking during pregnancy, parity and gestational age, it was estimated
      that MS tobacco smoke is to reduce the birth weight on average by about 210 g,
      however, in heavy smokers up to 450 g. The effect of SS tobacco smoke was to
      reduce birth weight by about 60 g after accounting for confounders. Both effects
      of active and passive smoking in pregnancy were statistically significant. When
      the self-reported smoking status was compared with plasma cotinine levels in
      women at delivery, a substantial misclassification error has been disclosed and
      it resulted mainly from the low sensitivity (47%) of the self-reported data on
      smoking status. This exposure bias may lead to a significant underestimation of
      correlation between low birth weight (< 2500 g) and tobacco smoking of mothers in
      pregnancy. Odds ratio (OR) corrected to exposure misclassification was much
      higher than the crude one (corrected OR = 8.0, crude OR = 2.9).

PMID- 8884059
TI  - Occupational tropical infectious and parasitic diseases in the Czech Republic.
AB  - The authors present a review on occupational tropical infectious and parasitic
      diseases notified in the Czech Republic in 1986 to 1995. They provide information
      on health care provided in the Czech Republic to working people travelling to
      areas demanding from the climatic and epidemiological aspect.

PMID- 8884060
TI  - Perspectives of tumour radiotherapy in the Czech Republic and "Oncology 2000"
      Foundation.
AB  - The incidence of tumours has still an increasing tendency. A great effort is
      being devoted to prevention as well as to improving early diagnosis and
      treatment. It is the radiotherapy which seems to bring new treatment
      possibilities at the present. Its goal consists in destroying all tumour cells in
      the target volume while all normal cells being damaged unsubstantially only. That
      is being achieved with standard available means only with rather great
      difficulties. However, in the last time two radiotherapy methods have been
      developed which are based on the use of the so called hadrons (i.e. particles
      exhibiting strong mutual interactions) and come nearer to the mentioned ideal
      goal of any tumour therapy. The first method consists in the application of beams
      of charged hadrons having a suitable characteristic of energy transfer; the most
      energy being transferred to the matter in the end of hadron tracks. Thus, by a
      suitable choice of initial energy of beam particles this maximum may lie in a
      tumour volume, while all other tissues obtain a smaller dose, the difference
      being greater when a multiple-field technique is used. The other approach
      (neutron capture therapy-NCT) makes use of epithermal (or thermal) neutrons
      captured by special isotopes accumulated in tumour cells with the help of
      suitable chemical carriers. Both the methods are now being introduced into
      clinical use in many countries. The "Oncology 2000" Foundation was grounded to
      introduce these methods into clinical use also in the Czech Republic. It proceeds
      with activities started by an interdisciplinary group of specialists formed
      approximately 20 years ago and having prepared some necessary conditions. As to
      the NCT a corresponding facility is now being finished and clinical tests are
      expected to be started in 1997. The main attention is now devoted to building up
      an oncology center based on the use of hadron beams.

PMID- 8884061
TI  - Assessing the effect of disease on nutrition of the preterm infant.
AB  - OBJECTIVE: To review existing data on nutritional requirements of extremely low
      birth weight (ELBW) and very low birth weight (VLBW) preterm infants (those who
      weigh < 1000 g and 1000-1500 g at birth, respectively), and the effects of
      diseases on these nutritional requirements. DATA SOURCES: A literature search was
      conducted on applicable articles related to nutritional requirements of preterm
      ELBW and VLBW infants and the effects of diseases in these infants on their
      nutritional and metabolic requirements. DATA SYNTHESIS: The literature was
      analyzed to determine nutritional requirements of preterm ELBW and VLBW infants,
      to select the most common diseases that have significant and important effects on
      nutrition and metabolism in these infants, and to make recommendations about
      diagnostic and therapeutic approaches to nutritional problems as affected by
      diseases in ELBW and VLBW infants. CONCLUSIONS: Many diseases unique to preterm
      infants, either directly or by enhancing the effects of stress on the metabolism
      of such infants, provide important changes in the nutrient requirements. The
      overriding observation from all studies, however, is that ELBW and VLBW preterm
      infants are underfed during the early postnatal period and that this condition,
      combined with additional stresses from various diseases, increases the risk of
      long-term neurological sequelae. The value of achieving a specific body
      composition and growth weight is less certain. There remains a critical need for
      determining the right quality as well as quantity of nutrients for these infants.

PMID- 8884062
TI  - Distinctive aspects of metabolism and nutrition in infancy.
AB  - OBJECTIVES: The effects of genes, the stage of development, and the environment
      on various metabolic processes in infancy are described. Some themes discussed
      cross these three boundaries. CONCLUSIONS: Certain substances not normally
      regarded as essential may become conditionally essential if their precursors are
      limited in the diet or, alternatively, if the processes of conversion are reduced
      in activity because of abnormal gene function, or developmental immaturity. Diet
      is a clear environmental influence but, because the nature of the diet is closely
      related to age, it is a developmental influence as well. Certain nutrients are
      followed from the diet, via the gut and intermediary metabolism through to
      individual tissues and the whole body. The relationships of diet, metabolism and
      brain function have attracted considerable investigation in recent years. In the
      right environment, with the correct genes, the processes of development will be
      smooth and without undue metabolic disturbance. Considerable variation can be
      accommodated within the elasticity of the systems, but some changes may lead to
      temporary, or even permanent, malfunction.

PMID- 8884063
TI  - Laboratory assessment of nutritional metabolic bone disease in infants.
AB  - OBJECTIVES: There are numerous laboratory investigations available for the
      assessment of an infant with suspected metabolic bone disease (MBD); thus,
      comprehensive laboratory investigations on every aspect of MBD would impose
      unnecessary stress to the infant and the costs involved would be prohibitive. An
      overview of the assessment of an infant with suspected MBD, in particular,
      nutrition-related bone disease, is presented. Our objectives include an
      understanding of: 1. the importance of appropriate information from history and
      physical examination to guide the laboratory investigations; 2. relevance and
      limitations of specific laboratory investigations: a. radiologic studies include
      diagnostic radiographs and quantitative bone mass determination by dual energy x
      ray absorptiometry, b. biochemical measurements to determine mineral homeostasis
      and bone turnover, c. vitamin (vitamin D metabolites) and hormonal (parathyroid
      hormone and calcitonin) measurements; with respect to diagnosis and monitoring of
      the natural progress or response to therapy. CONCLUSION: Relevant information
      from clinical history and physical examination, and an understanding of the role
      and limitations of various laboratory investigations, would allow the optimal
      utilization of laboratory tests in the assessment of an infant with MBD.

PMID- 8884064
TI  - Receptor assays in the clinical laboratory.
AB  - OBJECTIVE: To review the relative advantages/disadvantages of receptor assays
      versus immunoassays. REVIEW OF CURRENT LITERATURE RESULTS: The history of
      immunoassays is evaluated. Current shortcomings are emphasized. The present and
      future role of receptor assays is assessed. CONCLUSION: The author predicts a
      shift away from immunoassays to receptor assays for certain analytes such as
      Vitamin B12, folic acid and drugs that undergo extensive metabolism.

PMID- 8884065
TI  - Oxidation of fluorescent glycero- and sphingophospholipids in human plasma
      lipoproteins: alkenylacyl subclasses are preferred targets.
AB  - OBJECTIVES: Oxidation of polyunsaturated fatty acids in lipoproteins is supposed
      to play a crucial role at the early stages of atherogenesis. The polyunsaturated
      lipids (PUFAs) become oxidized and, thus, the degree and rate of lipid oxidation
      depend on their concentration and, probably, on the lipid moiety to which they
      are attached. DESIGN AND METHODS: To determine the relative oxidation
      susceptibilities of sphingo- and glycerolipid-bound fatty acyl chains, we used
      fluorescent analogs of the respective compounds, in which one natural fatty acyl
      chain was replaced by fluorescent diphenylhexatriene propionic acid. RESULTS:
      Oxidation susceptibilities of the fluorescent acyl chains in the presence of Cu2+
      or AAPH depended, in general, on the phospholipid to which they were bound and
      the lipoprotein. Phospholipids were oxidized faster in HDL than in LDL or Lp(a).
      Plasmalogens were more susceptible to oxidation than phosphatidylcholine and
      sphingomyelin. CONCLUSION: Thus, HDL and plasmalogens may be considered as
      preferred targets of lipid oxidation before the bulk of polyunsaturated
      phospholipids (mainly phosphatidylcholine) in LDL is subject to free radical
      attack.

PMID- 8884066
TI  - A method for the determination of type I iodothyronine deiodinase activity in
      liver and kidney using 125I-labelled reverse triiodothyronine as a substrate.
AB  - OBJECTIVES: A detailed method for the determination of iodothyronine deiodinase
      type 1 (DI-1) activity is described. The objective of the present method
      development was to consolidate the effective procedures of previous methods and
      produce an efficient assay that can be easily reproduced. DESIGN AND METHODS:
      This method uses a 5',-125I labelled rT3 as substrate and ion-exchange
      chromatography to separate released ionic iodine. Released 125I- collected in the
      eluate is counted, and the results used to calculate DI-1 activity. RESULTS:
      Results were found to be linear for tissue homogenates containing 3-11 mg
      protein.mL-1. Day-to-day coefficient of variation of liver homogenate was
      determined to be 13%. CONCLUSIONS: This method was found to be reliable,
      reproducible, and sample sizes as small as 10 microL could be readily assayed.
      The use of centrifuge filter units to contain the ion-exchange medium decreased
      handling of the material, and potential sources of error.

PMID- 8884067
TI  - Radioreceptor assay for sirolimus.
AB  - OBJECTIVES: To develop a radioreceptor assay (RRA) for sirolimus (rapamycin,
      RAPA). METHODS: A direct methanol extraction was used to prepare 45 patient
      samples for the RRA. Results were compared to the results obtained previously
      using high-performance liquid chromatography (HPLC). Between-run precision,
      recovery, and drug interference studies were also performed. RESULTS: The RRA is
      sensitive to 1.0 microgram/L RAPA equivalents in whole blood. Comparison with
      HPLC yielded a correlation coefficient for 45 patient samples of 0.977. Between
      run precision at 2.5, 7.5, 12.5, and 20 micrograms/L showed coefficients of
      variation (CVs) of 12.9, 9.2, 8.5, and 5.9%, respectively. Recoveries from the
      extraction procedure were 93% at 7.5 micrograms/L and 103% at 12.5 micrograms/L.
      Drug interference studies showed no interference in the RRA by cyclosporine
      (CsA), dexamethasone, prednisone, or methotrexate. CONCLUSION: We have
      demonstrated that the RRA for RAPA correlates well with HPLC, and has excellent
      precision and recovery. The procedure is far less time-consuming and complex than
      HPLC and has potential for automation.

PMID- 8884068
TI  - Comparison of three immunoassay kits for serum thyroglobulin in patients with
      thyroid cancer.
AB  - OBJECTIVES: This study describes the evaluation of performance of three
      immunoassay kits [Sanofi-Pasteur, IRMA, with five monoclonal antibodies; Wallac
      Delfia, FIA, with double monoclonal antibodies; and Diagnostic Products
      Corporation (DPC), RIA, with polyclonal antibodies] for serum thyroglobulin in
      patients with thyroid cancer. Specific aims were (a) to recognize a method with
      minimal interference, by comparing analyte recoveries, from thyroglobulin
      autoantibodies (TgAb) that can be present in some thyroid cancer patient samples,
      (b) to correlate individual results with those from Mayo Medical Laboratories
      (MML) (current referred out assay service used by our institute), and (c) to
      compare assay precision. METHODS: In evaluating performance of the three
      immunoassays, procedures were followed as recommended by the respective
      manufacturers. Parallel comparison of the three immunoassays with the MML
      procedure was performed with thyroid cancer patient sera. Recovery studies
      utilized sera from 15 thyroid cancer patients, 4 Hashimoto's thyroiditis
      patients, and 1 Grave's disease patient. TgAb were also measured directly by an
      IRMA thyroglobulin antibody kit (Sanofi-Pasteur). RESULTS: Among the randomly
      selected 20 samples assayed in parallel studies, low recoveries (< 80%) were
      present in 2 samples by IRMA assay (Sanofi-Pasteur), 8 samples by FIA assay
      (Wallac-Delfia), and 10 samples by RIA assay (DPC). The majority of the low
      recovery samples contained high titers of TgAb. All three kits correlated well
      with the Mayo method. At the control-1 level (approximately 9.9 microgram/L by
      Delfia determination), both the IRMA kit (CV = 1.96%, n = 10) and FIA Kit (CV =
      2.16%, n = 10) showed good within-run precision. CONCLUSIONS: In our hands, the
      IRMA Kit (Sanofi-Pasteur) demonstrated excellent precision, analyte recoveries,
      the least interference from TgAb, and good correlation with the Mayo Medical
      Laboratories procedure.

PMID- 8884069
TI  - Measurement of urinary oxalic acid: a comparison of five methods.
AB  - OBJECTIVE: Five methods for oxalate analysis in urine are compared with respect
      to reliability, accuracy, and practicability. RESULTS: Suppressed and
      unsuppressed ionchromatography, as well as the enzymatic Sigma-Kit, achieve low
      coefficients of variation for the within-batch imprecision (1.1-8.0%) and between
      day imprecision (1.6-7.2%). The results of these methods are comparable and the
      mean recovery rate ranges between 99.7% and 100.9%. The enzymatic Boehringer-Kit
      gives higher CV (3.1-9.5%) and the results are lower than those obtained by the
      methods mentioned above; the recovery rate is sufficient (92.4%). CONCLUSION: The
      handling of the chromatographic methods is very easy, whereas the enzymatic
      methods require more manual work. In relation to sample throughput, charges for
      the enzymatic methods are about twice as high as for the chromatographic methods.
      In respect to reliability and accuracy, the chromotropic acid method cannot be
      recommended (recovery rate 68%).

PMID- 8884070
TI  - Simultaneous detection and screening of T833C and G919A mutations of the
      cystathionine beta-synthase gene by single-strand conformational polymorphism.
AB  - OBJECTIVE: We used single-strand conformational polymorphism (SSCP) to screen for
      mutations at nucleotides 833 and 919 of the cystathionine beta-synthase (CBS)
      gene in 13 patients with homocystinuria and 11 of their relatives. METHODS: Exon
      8 of genomic DNA was selectively amplified by PCR using primers derived from
      intronic sequences of the human CBS gene. SSCP analysis was performed on the
      amplified products. Genotypes identified by SSCP were confirmed by DNA sequencing
      and an allele-specific PCR method. RESULTS: SSCP identified 5 patterns
      corresponding to five genotypes. We confirmed that the different genotypes result
      from mutations at nucleotides 833 and 919 of the CBS gene, and that these 2
      mutations account for approximately 50% of affected alleles in homocystinuria
      patients. CONCLUSION: Our recent elucidation of intron-exon borders and intronic
      sequences of the CBS gene has made possible the use of SSCP to screen for
      known/unknown mutations in the CBS gene. Because T833C and G919A represent the
      two most common mutations and both are located within exon 8 of the CBS gene,
      SSCP of exon 8 allows screening of the heterozygous carrier state of these
      mutations in a large population, to determine the importance of heterozygosity of
      CBS mutations as the cause of mild hyperhomocyst(e)inemia associated with
      premature vascular diseases.

PMID- 8884071
TI  - Low-density lipoprotein composition and oxidability in atherosclerotic
      cardiovascular disease.
AB  - OBJECTIVES: To characterize low-density lipoprotein (LDL) chemical composition
      and oxidability in normolipidemic and dyslipidemic patients with atherosclerotic
      cardiovascular disease, as compared with matched control subjects. To evaluate
      LDL susceptibility to oxidation, we determined the cutoff points of
      thiobarbituric reactive substances (TBARS) in LDL after oxidative stress, as well
      as its resistance to oxidation. DESIGN AND METHODS: LDL (density 1.019-1.063
      g/mL) of 24 men with atherosclerotic cardiovascular disease (12 normolipidemic
      and 12 dyslipidemic patients) and 18 age-matched healthy control men. LDL
      chemical composition was determined and apo B/cholesterol ratio was calculated.
      TBARS in native LDL and after 60 and 120 min of LDL oxidation with copper were
      measured. The conjugated diene production kinetics during LDL incubation with
      copper were also studied, lag time being an oxidation resistance marker. Cutoff
      points for the positivity criterion of apoB/cholesterol ratio in LDL and TBARS in
      native and oxidized LDL were evaluated using the receiver operator characteristic
      (ROC) graphic method. RESULTS: LDL were triglyceride-enriched, the
      apoB/cholesterol ratio being higher in patients than in controls, without
      differences between normolipidemic and dyslipidemic subgroups. We have
      established the following cutoff values to differentiate between patients and
      controls: 0.43 mg/mg for the apo B/cholesterol ratio in LDL; 3.0 nmol
      malondialdehyde/mg protein for TBARS in native LDL; 22 and 80 nmol
      malondialdehyde/mg protein after 60- and 120-min postoxidative stress,
      respectively. We did not find differences in the conjugated diene production
      kinetics between patients and controls. CONCLUSIONS: The enrichment in
      triglycerides and the high apoB/ cholesterol ratio suggest the presence of an
      abnormal LDL particle in normolipidemic and dyslipidemic patients. This LDL
      particle was more susceptible to oxidation. In the ROC analysis, the TBARS plot
      at 120 min exhibited greater accuracy and better performance than the other LDL
      oxidability markers.

PMID- 8884072
TI  - IFCC-standardized pediatric reference intervals for 10 serum proteins using the
      Beckman Array 360 system.

PMID- 8884074
TI  - Creatine kinase-MB by immunoinhibition in the diagnosis of suspected acute
      myocardial infarction.

PMID- 8884073
TI  - Suitability of lithium heparinate plasma for the measurement of selected analytes
      on Beckman Synchron CX analyzers.

PMID- 8884075
TI  - Deletion or triplication of the alpha 3 (VI) collagen gene in three patients with
      2q37 chromosome aberrations and symptoms of collagen-related disorders.
AB  - Two new cases of del(2)(q37.1) and one case of partial trp(2)(q37) are studied by
      FISH with cosmid probes from the COL6A3 and PAX3 genes mapped in 2q37.3 and 2q36,
      respectively. While the PAX3 gene dosage appeared unaffected, the COL6A3 gene was
      found to be deleted and triplicated, respectively. This finding could explain
      features of connective tissue disorders such as joint laxity and hypotonia or
      joint stiffness and epiphyseal dysplasia, particularly documented by congenital
      dislocation of the radial head. Karyotype-phenotype correlations with reference
      to published cases are discussed.

PMID- 8884076
TI  - Ehlers-Danlos syndrome type IV caused by Gly400Glu, Gly595Cys and Gly1003Asp
      substitutions in collagen III: clinical features, biochemical screening, and
      molecular confirmation.
AB  - Three patients with Ehlers-Danlos syndrome type IV (EDS IV) and biochemical
      evidence of structural defects in collagen III were investigated for mutations
      within the collagen III gene (COL3A1). Single strand conformation polymorphism
      analysis of alpha 1 (III) cDNA indicated the presence of different heterozygous
      sequence changes in each of the patients. Nucleotide sequencing revealed
      mutations leading to the substitution of glycine 400 with glutamic acid, glycine
      595 with cysteine, and glycine 1003 with aspartic acid. EDS IV is a life
      threatening disorder which, as the clinical histories of our patients and their
      families show, still often escapes diagnosis. Biochemical and molecular studies
      can clarify the diagnosis and help provide appropriate management and
      counselling.

PMID- 8884077
TI  - Four siblings with achalasia, alacrimia and neurological abnormalities in a
      consanguineous family.
AB  - Four siblings with achalasia, alacrimia and other problems involving the
      autonomic nervous system involvements are reported. Achalasia and alacrimia were
      present in all of them. Their parents are first cousins and have four other
      healthy children. Electrophysiological tests showed that autonomic dysfunction
      has progressed with age. Blood cortisol levels were normal in all four affected
      children. Depending on those findings of our case and previous reports, we
      conclude that triple-A syndrome and achalasia, alacrimia with or without
      neurological abnormalities could be variable manifestations of the same autosomal
      recessive gene defect.

PMID- 8884078
TI  - Branchio-oto (BO) syndrome and oculo-auriculo-vertebral phenotype: overlapping
      clinical findings in a child from a BO family.
AB  - A three-generation BO family is presented: the proband showed, in addition to
      branchio-oto malformations, a severe condition with growth retardation,
      mandibular hypoplasia and vertebral anomalies resembling the oculo-auriculo
      vertebral (OAV) phenotype. This family study supports the hypothesis of Rollnick
      and Kaye that the OAV spectrum may represent, in some cases, an extreme component
      of the BOR syndrome. The finding has relevant implications for genetic
      counselling regarding both conditions.

PMID- 8884079
TI  - A de novo interstitial deletion of chromosome 15 band q25 as revealed by FISH
      technique.
AB  - We report a new chromosomal finding in a 20 month-old girl. The minor clinical
      features included: moderate mental retardation, microcephaly, mild hypotonia and
      hypertelorism. Initially, what appeared to be a terminal deletion of the long arm
      of one chromosome 15 [15q26-->qter] was determined to be an interstitial deletion
      involving band 15q25 as revealed by FISH-technique, showing the presence of
      intact telomeric hybridization signals. The cytogenetic diagnosis was thus
      modified to 46,XX, del (15) (pter-->q24::q26--> qter). Nevertheless, the function
      of the enzyme telomerase should not be ignored, as healing could occur following
      such terminal deletions. Consequently, it will remain a difficult task to
      distinguish terminal deletions from those that are interstitial.

PMID- 8884080
TI  - Interstitial 6q deletion and Prader-Willi-like phenotype.
AB  - A third case of an interstitial deletion of the long arm of chromosome 6 with
      clinical features mimicking Prader-Willi syndrome (PWS) is presented. Although
      preliminary clinical evaluation in each case suggested PWS, further review
      revealed that the features in all three cases are not completely compatible with
      the characteristic findings in Prader-Willi syndrome. Furthermore, the deletions
      in the three cases do not show a consistent region of overlap. Consequently, no
      particular band or region in 6q can be defined as associated with obesity.
      However, our findings confirm the suggestion of Villa et al. in 1995, that
      individuals with a PWS phenotype who are cytogenetically and molecularly negative
      for a deletion of 15q11-q13 should be examined for a deletion of 6q.

PMID- 8884081
TI  - Fibular dimelia and mirror foot without associated anomalies.
AB  - Fibular dimelia with mirror foot is a rare anomaly that may be associated with
      additional anomalies such as ulnar dimelia, facial abnormalities and
      sacrococcygeal teratoma. We report a female child with unilateral tibial aplasia,
      ipsilateral duplication of fibula and calcaneus, and mirror polydactyly of the
      foot without associated abnormalities.

PMID- 8884082
TI  - Bloom's syndrome in a Turkish individual.

PMID- 8884083
TI  - Partial trisomy 6p due to maternal t(1;6) translocation.
AB  - Partial trisomy 6p with duplications ranging from 6p21 to 6p25 is emerging as an
      established syndrome. A case of duplication of segment p22-p25 of the short arm
      of chromosome 6 as the result of a maternal t (1;6)(q44;p22.2) translocation in a
      mentally retarded girl with congenital anomalies is reported here. The associated
      phenotypic anomalies are compared with other reported cases of duplication 6p
      involving adjacent regions.

PMID- 8884084
TI  - A female with monosomy 18 mosaicism: a previously undescribed chromosome
      abnormality.
AB  - We report on a patient with monosomy 18 mosaicism, a previously undescribed
      chromosome abnormality. The phenotype is reminiscent of chromosome 18 ring
      mosaicism. The reason that the patient survived may be attributed to low level
      mosaicism for the monosomy.

PMID- 8884085
TI  - Four frequently observed polymorphisms in the 3'-UTR of human peripheral myelin
      protein 22 (PMP22): identification of different haplotypes.

PMID- 8884086
TI  - A Stu I polymorphism in the human androgen receptor gene (AR).

PMID- 8884087
TI  - Homozygous deletion of exon 18 leads to degradation of the lysosomal alpha
      glucosidase precursor and to the infantile form of glycogen storage disease type
      II.
AB  - We describe two unrelated Dutch patients with typical symptoms of infantile
      glycogen storage disease type II (GSD II) and virtual absence of acid alpha
      glucosidase activity in leukocytes and cultured skin fibroblasts. The patients
      were identified as homozygotes for a deletion of exon 18 of the acid alpha
      glucosidase gene (GAA). The in-frame deletion manifests at the protein level in a
      characteristic way: the enzyme precursor is smaller than normal and degraded in
      the endoplasmic reticulum or Golgi complex. These case present an evident example
      of a genotype-phenotype correlation in glycogen storage disease type II.

PMID- 8884088
TI  - Duodenal web in the syndrome of osteopathia striata with cranial sclerosis.

PMID- 8884089
TI  - Ataxia telangiectasia syndrome with B cell lymphoma.

PMID- 8884090
TI  - The syndrome of delayed posthemiplegic hemidystonia, hemiatrophy, and partial
      seizure: clinical, neuroimaging, and motor-evoked potential studies.
AB  - Magnetic motor-evoked potential (MEP) study of patients with the syndrome of
      delayed posthemiplegic hemidystonia, hemiatrophy, and partial or hemi-seizures
      ('4-hemi' syndrome) has not been described. Among 35 patients investigated for
      posthemiplegic movement disorders from February 1988 to January 1995, seven
      showed '4-hemi' syndrome. Clinical work-up, magnetic resonance images (MRI)
      and/or computed tomography (CT) were performed in all. Transcranial MEP studies
      were done in five patients. The remote causes of '4-hemi' syndrome were neonatal
      stroke, trauma, and encephalitis in infancy. The dystonia may occur as long as a
      decade after the initial insult. MRI or CT showed destructive lesion in the
      contralateral putamen (five patients), caudate (four), thalamus (five), and
      atrophy of the contralateral hemisphere (five). Other associations were
      porencephalic cyst. Wallerian degeneration, and asymmetric compensatory
      ventriculomegaly. MEP showed abnormalities in the affected upper limbs in four of
      five patients. The abnormalities were reduced amplitude of the compound muscle
      action potential following cortical stimulations with or without temporal
      dispersion, and with or without prolongation of its latency. The peripheral motor
      conductions following cervical stimulations were normal. MEP abnormalities may
      not be related to the hemiatrophy and the size of brain lesion per se. The
      hemidystonia is static after the second decade of life, and it is often difficult
      to treat.

PMID- 8884091
TI  - Treatment choices of 119 patients with hemifacial spasm over 11 years.
AB  - A retrospective study of patients with hemifacial spasm (HFS) was performed in
      order to determine long-term treatment choices: local botulinum toxin, type A,
      injections, oral pharmacologic agents, and surgery (neurosurgical decompression
      of the seventh nerve at the brainstem level and upper eyelid blepharoplasty). Of
      119 patients with diagnosed hemifacial spasm in the Oculoplastics Division of the
      Department of UMD-New Jersey Medical School, Newark, NJ from September, 1983, to
      June 1, 1994, 108 were initially treated with 735 botulinum toxin injections.
      Forty-seven of the 108 patients (43.5%) initially treated at our institution
      received 459 injections for a median treatment period of 59 months per patient.
      Eight patients (7.4%) continued treated elsewhere and four other patients were
      injected at our institution until their death from other causes. Twenty-two
      patients (20.4%) were lost to followup after receiving 117 injections. Five
      patients (4.6%) had spontaneous resolution of their condition after botulinum
      toxin therapy and nine patients (8.3%) chose not to receive any additional
      injections or other treatment. Thirteen patients (12.0%) did not respond
      adequately to botulinum injections and 10 such patients obtained relief from
      treatments other than botulinum toxin: oral pharmacologic agents (two patients),
      neurosurgical decompression of the seventh nerve (two patients), and upper eyelid
      blepharoplasty (one patient). In addition to botulinum injections, 15 patients
      required adjunctive minor tranquilizers and/or antiseizure medications. Botulinum
      A toxin is an excellent long-term treatment of hemifacial spasm. This condition
      may occasionally spontaneously resolve after botulinum therapy.

PMID- 8884092
TI  - Subependymal giant cell astrocytoma associated with tuberous sclerosis:
      diagnostic and surgical characteristics of five cases with unusual features.
AB  - Five children with tuberous sclerosis and intracranial tumors were surgically
      treated at Neurosurgery Department of Hacettepe University School of Medicine.
      Two of the five patients presented with the giant cell astrocytoma filling the
      third ventricle. Direct surgical intervention and tumor removal was carried out
      in all four patients (three with a total surgical resection and one with a
      subtotal resection) and cerebrospinal fluid shunting procedure in one.
      Histopathological examination revealed giant cell astrocytomas in four patients.
      Postoperatively, one died and the rest four patients survived with minor focal
      neurologic difficulties. The surgical results and the changing concepts in the
      treatment of tuberous sclerosis are discussed and the literature is reviewed.

PMID- 8884094
TI  - Reversible cerebellar gait ataxia with postural tremor during episodes of high
      pyrexia.
AB  - We describe five patients presenting with high fever and isolated cerebellar gait
      ataxia. In all these patients, neurological examination revealed dysmetria,
      intention tremor and postural tremor during sustained posture, all restricted to
      the legs. Brain MRI was normal. In four of these patients, the recording of leg
      tremor during sustained postures showed a 3-Hz frequency. Cerebellar gait ataxia
      resolved within 3-10 days. We suggest that the ataxic gait was due to a
      reversible dysfunction of the spinocerebellar part of the anterior lobe.

PMID- 8884093
TI  - The effect of gonadectomy on the clinical course of chronic experimental allergic
      encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is an animal model for the human
      neurological disease multiple sclerosis (MS). Upon immunization with guinea pig
      spinal cord under a low dose of Cyclosporin A, male Lewis rats develop a severe
      chronic (relapsing) course of EAE (CR-EAE). By contrast, female Lewis rats
      develop a more mitigated course of EAE: only half of the female rats develop
      relapses. To further analyze factors determining this sexual dimorphism in the
      course of EAE, in the present study male and female Lewis rats were
      gonadectomized before induction of CR-EAE. Now both male and female rats all
      developed a severe chronic course of EAE, showing extensive pathological changes
      in the CNS. In the female sham-gonadectomy (control) group only one third of the
      rats developed relapses. These female rats only showed mild pathological changes
      in the CNS. In the male sham-gonadectomy (control) group all rats developed
      relapses of EAE and showed extensive pathological changes in the CNS. From these
      data we conclude that the presence of the ovaries (partially) protects female
      rats against relapses of EAE and CNS injury. Presence or absence of the testes
      apparently makes no difference on the course of EAE. We propose that sex hormones
      produced in the ovaries protect female rats against relapses of EAE and
      underlying CNS injury.

PMID- 8884095
TI  - The prognostic value of cortical magnetic stimulation in acute middle cerebral
      artery infarction compared to other parameters.
AB  - The prognostic value of magnetic evoked potentials (MEP), somatosensory evoked
      potentials (SSEP), age and radiological parameters was determined in 50 patients
      with acute middle cerebral artery infarction. We performed MEP and SSEP within 4
      days and after 6 weeks and 3 months of the infarction and assessed clinical
      improvement by using the Barthel index (BI) and the Rankin scale. The
      localization and extent of the infarction was investigated by CT scanning or NMR.
      All parameters were correlated to clinical outcome and the prognostic
      significance of each parameter in addition to BI was determined. MEP, SSEP, and
      age were valuable prognostic parameters in predicting stroke outcome when used
      together with the BI. However, in stepwise regression analysis using all
      parameters simultaneously, only MEP and age significantly contributed to clinical
      outcome in addition to BI. Patients showed a better outcome when their MEP was
      normal or delayed, measured within 4 days of the infarction, compared to patients
      with absent MEP. Clinical outcome was better at a younger age.

PMID- 8884096
TI  - Epileptic blindness in children: a localizing sign of various epileptic
      disorders.
AB  - The ictal manifestations, EEG, CT, and MRI correlates, as well as the management
      and outcome of 11 children with epileptic blindness are presented. Seven males
      and four females, aged 3 months to 12 years, experienced single or recurrent
      episodes of acute visual obscuration. Ictal blindness was the solitary epileptic
      phenomenon in only two children. The rest had other focal or generalized motor
      epileptic manifestations. Six children had either focal motor phenomena and/or
      unilateral EEG disturbances, with a normal head CT. The drug of choice in this
      group was carbamazepine and all became asymptomatic. Two patients had structural
      abnormalities of the brain, of which one had a low-grade occipital astrocytoma
      which was resected. His blindness abated shortly following initiation of
      carbamazepine, even prior to surgery. Status epilepticus amauroticus and focal
      motor seizures, secondary to focal cortical dysplasia, was detected in another 3
      month-old infant. These required cortical resection and she regained full vision.
      Three patients had generalized epileptiform discharges on EEG, of which two were
      photic-induced. Blindness was accompanied with motor seizures and myoclonic
      jerks. Full seizure control could be achieved in only one child. CONCLUSION: our
      data suggest a relatively benign nature and a favorable outcome in most children
      with ictal blindness. Resection of a secondary temporo-parietal focus, as
      occurred in an infant with status epilepticus amauroticus which originated in the
      occipital region, may result in complete cessation of seizures and visual
      recovery.

PMID- 8884097
TI  - Hepatic myelopathy. Case report with review of the literature.
AB  - Hepatic myelopathy is a rare complication of hepatic insufficiency, causing
      progressive spastic paraparesis. There are few reports detailing the clinical and
      diagnostic aspects of this uncommon cause of neurological deterioration in
      patients with liver disease. Early recognition of this disorder will become more
      important as patients with liver disease survive longer due to medical advances,
      including liver transplantation. We present an additional patient with hepatic
      myelopathy associated with infantile portal vein thrombosis and review the
      previous reports of hepatic myelopathy in the English literature.

PMID- 8884098
TI  - Chorea in primary antiphospholipid syndrome.
AB  - A 12-year-old girl with chorea, thrombocytopenia and false positive VDRL had
      negative serological tests for SLE, but high titre of antiocardiolipine
      antibodies. Primary antiphospholipid antibody syndrome is rarely complicated by
      chorea, but should be taken into consideration in patients who do not fulfill the
      diagnostic criteria for SLE.

PMID- 8884099
TI  - Primary monophasic synovial sarcoma of the brachial plexus: report of a case and
      review of the literature.

PMID- 8884100
TI  - Basal ganglionic angioleiomyoma.
AB  - A rare case of basal ganglionic angioleiomyoma in a 12-year-old girl is reported.
      She presented with features of raised intracranial tension, multifocal seizures,
      left hemidystonia and apraxia of eyelid closure. Cranial CT scan showed a large
      hypodense lesion with an enhancing mural nodule in the region of head of the
      caudate nucleus on the right side. The lesion was extending to the posterior limb
      of internal capsule postero-medially and to globus pallidus laterally. Another
      small, hyperdense, enhancing lesion was seen in the region of globus pallidus on
      the left side. The right basal ganglionic mass was excised through frontal
      craniotomy. Histopathological, Immunocytochemical and Ultrastructural examination
      of the right basal ganglionic mass showed features characteristic of
      angioleiomyoma. Following surgery the patient improved initially with respect to
      dystonia but worsened later on. Repeat cranial CT, 20 months after surgery,
      showed bilateral frontotemporal atrophy without any tumor recurrence while the
      lesion on the left side remained quiescent.

PMID- 8884101
TI  - Optic nerve glioma mimicking an optic nerve meningioma.
AB  - The case is described of an optic nerve glioma, mimicking an optic nerve
      meningioma in a man aged 41 years. CT, MRI and DSA revealed an enhancing tumor
      surrounding the optic nerve. Histopathologic examination of the removed optic
      nerve revealed a centrally located glioma surrounded by normal optic nerve
      fibres.

PMID- 8884102
TI  - Tick-borne encephalitis complicated by a polio-like syndrome following a holiday
      in central Europe.
AB  - We report a case of Central European tick-borne encephalitis (CETE) in a 54-year
      old man, presenting with fever and neurological complications following a holiday
      in Austria. A disease resembling paralytic poliomyelitis may develop with upper
      and lower extremity paralysis, as is the case in our patient. Our patient was
      most likely infected by eating goat's cheese, made of unpasteurised goat's milk.
      The diagnosis was confirmed by a positive IgM antibody response to the virus in
      the serum.

PMID- 8884103
TI  - FK 506 therapy for refractory renal allograft rejection: lessons from liver
      transplantation.
AB  - FK 506 has proven to be an effective immunosuppressive agent in liver
      transplantation, but its role in renal transplantation remains to be defined.
      Since the initial availability of FK 506 for treatment of refractory renal
      allograft rejection, we have applied an aggressive approach consisting of
      institution of rescue therapy at an early point in the rejection process combined
      with assiduous monitoring of FK 506 blood levels and the histologic response to
      therapy. A total of 17 adult patients were treated for refractory renal allograft
      rejection with this approach. Median follow-up was 9 months post-initiation of FK
      506 therapy. Median time to first rejection was 26 d post-transplant, and median
      time to FK 506 rescue therapy was 113 d post-transplant. Sixteen of 17 patients
      received either ATGAM or OKT3 induction therapy. Prior to FK 506 rescue therapy,
      patients received the following antirejection therapy: corticosteroids 40 + 21
      mg/kg (prednisone or Solumedrol), OKT3 (median 14 d), ATGAM (3 patients, 14 d
      each). FK 506 rescue therapy was successful in reversing the rejection process in
      all 17 patients. Fifteen patients (88%) demonstrated rapid reversal of rejection
      (i.e. reversal within 14 d), whereas three patients demonstrated delayed
      reversal. Nine month actuarial patient and graft survivals were 92% and 84%. When
      censored for documented noncompliance, nine month actuarial graft survival was
      92%. Good long-term renal function was observed (pre-FK 506 baseline creatinine
      2.1 +/- 0.5 mg/dl, current serum creatinine 2.1 +/- 0.6 mg/dl. Six recurrent
      rejection episodes occurred in 5 patients (29%) with a median time to recurrent
      rejection of 59 d post-initiation of FK 506 rescue therapy. Each recurrent
      rejection episode was successfully treated by corticosteroids and/or increased FK
      506 dose. CMV disease and lymphoma were not observed. Histologic evidence of FK
      506 nephrotoxicity (hyaline necrosis in preglomerular arterioles) was observed in
      6 patients 30% (median time to diagnosis 49 d). FK 506 blood levels (whole blood
      TDX) between 10 and 20 ng/ml provided effective reversal in most patients.
      Current FK 506 dose and blood levels are 0.18 +/- 0.09 mg/kg/d and 7 +/- 2
      ng/dl). FK 506 rescue therapy also allowed aggressive reductions in prednisone
      dose: (mean current prednisone dose 0.08 +/- 0.05 mg/kg/d). In conclusion, an
      aggressive approach toward FK 506 rescue: 1) provides prompt, effective reversal
      of refractory renal allograft rejection, 2) good long-term renal allograft
      function, 3) balanced immunosuppression with respect to recurrent rejection,
      opportunistic infection and PTLD, 4) acceptable toxicity, and 5) aggressive
      reduction in corticosteroid dosing. Based on these findings, FK 506 rescue
      therapy is now the treatment of choice in our program for renal allograft
      rejection episodes that occur following antilymphocyte antibody therapy.

PMID- 8884104
TI  - Simultaneous ureterocystoplasty and living related renal transplantation.
AB  - Enterocystoplasty in preparation for renal transplantation in children with
      severely dysfunctional bladders is widely accepted by pediatric urologists and
      transplant surgeons alike. The risk for septic and other complications in this
      immunosuppressed population remains elevated however, since problems inherent to
      the use of bowel or stomach in the urinary tract become magnified in these
      patients. In addition, simultaneous enterocystoplasty and transplantation carry a
      significant risk, and we must therefore subject these children to two major
      operations within a short time span. We herein describe our experience with
      combining simultaneously ureterocystoplasty and renal transplantation in a child.
      We believe this procedure has major relevance, in particular in the group of
      patients with posterior urethral valves and chronic renal failure.

PMID- 8884105
TI  - Captopril-induced changes in effective renal plasma flow in hypertensive renal
      transplant recipients.
AB  - The role of converting enzyme inhibitor enhanced radionuclide investigations in
      post-transplant hypertension is not clearly defined. Presence of renal failure,
      chronic rejection and use of cyclosporin A complicates the results. Captopril
      induced changes in effective renal plasma flow (ERPF) were studied in 10 patients
      with severe post-transplant hypertension and no evidence of rejection.
      Angiographic correlation was available in all. Six patients had a significant
      increase in ERPF after captopril, and all had a negative angiogram. One patient
      on CsA with a negative angiogram had no change in ERPF. Three patients had a fall
      in ERPF, and all 3 had transplant renal artery stenosis. Captopril-induced
      changes in ERPF can differentiate patients with native-kidney-induced
      hypertension from those with hypertension secondary to transplant renal artery
      stenosis in patients without evidence of rejection.

PMID- 8884106
TI  - Anatomical and physiological problems of Segment IV: liver transplants using left
      lobes from living related donors.
AB  - We reviewed the problem of Segment IV in using left lobes from living related
      donors, in 18 left-lobe transplants performed on pediatric patients who ranged in
      age from 6.0 to 17.3 yr, and in body weight from 19.8 to 58.0 kg. The separate
      monitoring of oxygen saturation of hemoglobin in the liver sinusoid of segments,
      using a spectrophotometric technique, demonstrated a delay in re-oxygenation of
      Segment IV after the portal reflow, and revealed its return to comparable
      oxygenation with Segments II and III by the re-arterialization. Hemoglobin
      content, which was determined by the same technique, occasionally increased in
      Segment IV during the operation, implying sluggish microcirculation caused by
      inadequate hepatic venous drainage. These characteristic profiles on tissue
      oxygenation and hemodynamics in Segment IV should be considered when using left
      lobes as living related liver grafts.

PMID- 8884107
TI  - Interferon-alpha therapy for hepatitis C virus recurrence after liver
      transplantation: long-term response with maintenance therapy.
AB  - Interferon-alpha is currently the only available treatment for HCV hepatitis. We
      assessed the safety and efficacy of 6 month course of interferon therapy in 18
      consecutive liver transplant recipients with recurrent HCV hepatitis and report
      the long-term response with maintenance interferon. Median follow-up after the
      institution of interferon was 24 months. Complete response was defined as
      normalization of both aspartate and alanine aminotransferase. Complete response
      after 6 months of interferon was observed in 28% (5/18); an additional 33% (6/18)
      of the patients were late responders. Overall, 61% (11/18) of the patients had
      long-term sustained normal response at a median follow-up of 24 months. Long-term
      sustained response was observed in 73% (8/11) of the patients who continued
      interferon beyond 6 months vs. 43% (3/7) in those who received 6 months of
      interferon. Fatigue, headache and cytopenia were the most commonly observed side
      effects occurring in 39%, 22% and 28% of the patients, respectively.
      Discontinuation of interferon, however, was not required in any of the patients.
      Rejection was documented in 6% (1/18) patients receiving interferon; this
      incidence was not higher than rejection episodes occurring > 6 months post
      transplant in other recipients transplanted during the same period and who did
      not receive interferon. Responders had a trend towards later recurrence of HCV
      hepatitis after transplantation. In conclusion; maintenance interferon was well
      tolerated and appeared to improve the long-term outcome in our patients; however,
      future studies should evaluate this in a controlled trial.

PMID- 8884108
TI  - The quest for living-related kidney donors for children with end-stage renal
      disease.
AB  - In a pediatric renal transplant program that actively seeks living-related kidney
      donors, we achieved a living donor rate of 55% in 119 children. This approximates
      the national average but is less than an idealized goal. For black children, the
      living-donor transplant rate was 41%, a disconcertingly low rate. In an attempt
      to define factors that negatively affected living-related donor availability, we
      analyzed our evaluation process by distinct phases (interview, histocompatibility
      testing and medical evaluation). We classified our families on the basis of
      locale (urban, suburban and rural), family unit (two or less parents, adult sibs
      or other relatives presenting at interview) and economic status (designating only
      economic-disadvantaged and other). While histoincompatibility is predictably a
      negative factor, the negative impacts of medical illness in the donor pool,
      economic disadvantage and single parent family are striking and cumulative. Our
      data validate the relative success of an aggressive recruitment policy in a
      patient population that includes many economically disadvantaged families. For
      pediatric renal transplant programs with low living-related donor rates, our data
      should encourage review and possible modification of the donor recruitment
      process.

PMID- 8884109
TI  - Hematopoietic cell transplantation for the induction of allo- and xenotolerance.
AB  - Durable tolerance can be reliably achieved by inducing engraftment of allogeneic
      or xenogeneic hematopoietic cells in recipients initially depleted of T
      lymphocytes. Engraftment of pluripotent hematopoietic stem cells (PPHSC) provides
      a constant supply of donor antigen to ensure the ongoing central deletion of
      donor-reactive T cell clones, resulting in a permanent state of donor-specific
      tolerance. Because of the toxicity of myeloablative therapy used to achieve
      allogeneic PPHSC engraftment, this approach has not yet been applied in humans.
      However, a non-myeloablative, relatively non-toxic conditioning regimen allowing
      allogeneic or concordant xenogeneic bone marrow engraftment and tolerance
      induction has recently been developed in a murine model. Host pre-treatment with
      depleting doses of anti-CD4 and anti-CD8 mAbs (and in the xenogeneic combination,
      anti-Thy 1.2 and anti-NK 1.1 mAbs), followed by 3 Gy whole body irradiation (WBI)
      and 7 Gy of thymic irradiation (TI) allows engraftment of allogeneic or
      xenogeneic rat bone marrow cells with mixed, multilineage lymphohematopoietic
      chimerism and donor-specific skin graft tolerance. TI can be omitted from the
      regimen if additional mAb treatments are given. Engraftment of allogeneic PPHSC
      is associated with early migration of donor bone marrow-derived cells to the host
      thymus, resulting in deletion of developing thymocytes with reactivity to donor
      antigens. Maintenance of long-term tolerance is purely due to this deletional
      mechanism. In the xenogeneic rat-->mouse species combination, mixed chimerism is
      also associated with deletional T cell tolerance, and also leads to tolerance at
      the level of B cells that make natural antibodies. In the discordant pig-->mouse
      species combination, we have found that physiologic preference for host
      hematopoiesis is a major barrier to achieving donor hematopoietic reconstitution.
      Pig-specific hematopoietic cytokines can at least partially overcome this
      barrier. Furthermore, if normal, immunocompetent mice are thymectomized, then
      receive T- and NK-cell-depleting mAbs, and a fetal swine thymus is grafted,
      murine CD4 T cells recover in the swine thymus, and demonstrate specific
      tolerance to the xenogeneic swine donor. These T cells appear to be able to
      recognize antigen in the context of host MHC, and demonstrate immunocompetence.
      Our studies have demonstrated for the first time that donor-specific skin graft
      tolerance can be induced across a discordant species barrier.

PMID- 8884110
TI  - Microemulsion technology in the reformulation of cyclosporine: the reason behind
      the pharmacokinetic properties of Neoral.
AB  - Management of transplant patients receiving cyclosporine therapy is complicated
      by interpatient and intrapatient variability in pharmacokinetic parameters caused
      by the drug's unpredictable bioavailability. Cyclosporine, a highly lipophilic
      cyclic polypeptide, has recently been reformulated using a microemulsion delivery
      system to improve its bioavailability. This new orally administered formulation,
      Neoral (cyclosporine capsules and oral solution for microemulsion), has self
      emulsifying properties and spontaneously forms a microemulsion (particle size <
      0.15 microns) in the aqueous fluids of the gastrointestinal tract. Clinical
      trials in renal transplant recipients, liver transplant recipients with external
      biliary diversion, and healthy volunteers have demonstrated enhanced
      bioavailability and greatly improved dose linearity with the cyclosporine
      microemulsion compared with the original cyclosporine formulation, Sandimmune
      (cyclosporine). The rate and extent of absorption were greater with the
      cyclosporine microemulsion under both fasting and nonfasting conditions, and
      there was a more consistent relationship between the administered dose and area
      under the time-concentration curve. Early clinical efficacy trials in renal and
      liver transplant recipients have shown no difference in the incidence or severity
      of drug-related adverse events. Studies on the long-term efficacy and safety of
      the new microemulsion formulation are ongoing.

PMID- 8884111
TI  - Two cases of Kaposi's sarcoma in renal and liver transplant recipients treated
      with interferon.
AB  - We report two cases of Kaposi's sarcoma in recipients of solid organ transplants,
      presenting (Case 1) 12 months after liver transplantation and (Case 2) 7 months
      after kidney transplantation. Both patients share the following features: natives
      from the Mediterranean area (Southern Italy), multiple immunosuppressive regimen,
      infection with hepatitis B and cytomegalovirus. During the 3 yr of follow-up
      after the diagnosis, their immunosuppressive regimen was reduced and they were
      treated with alpha interferon with remission of the clinical findings. The
      management of Kaposi's sarcoma in organ transplant recipients remains a
      controversial issue because of the risks of organ rejection associated with the
      reduction of immunosuppression and with the use of interferon.

PMID- 8884112
TI  - Analysis of ICAM-1 and HLA-DR expression on renal allograft aspirates.
AB  - ICAM-1 and HLA-DR expressions were studied on parenchymal cells obtained by
      aspirative biopsies of renal allografts. Patients were evaluated during 3 months
      after transplantation. Conventional cytology and immunoperoxidase stainings using
      anti-ICAM-1 and anti-HLA-DR antibodies were employed. The value of the total
      corrected increment was significantly higher (p < 0.05) during acute rejection
      episodes than during acute tubular necrosis or stable renal function. The
      percentage of HLA-DR positive cells were higher in rejection than in stable
      function periods (p < 0.05). The percentage of ICAM-1 positive cells was higher
      in rejection than in acute tubular necrosis periods (p < 0.05). The sensitivities
      to the diagnosis of rejection were 71.8% (TCI), 68.4% (ICAM-1) and 55.0% (HLA
      DR). The specificities were 87.3%, 81.3% and 68.4% respectively. Combinations of
      the tests resulted in increased sensitivity. We concluded that the use of these
      monoclonal antibodies improves the sensitivity of conventional aspiration
      cytology to the diagnosis of acute renal rejection.

PMID- 8884113
TI  - Comparison of two antilymphocyte globulins replacing cyclosporin A after first
      kidney allotransplantation and prolonged graft ischemia.
AB  - ATG/Fresenius (5 mg/kgBW) and ATGAM (Upjohn, 12.5 mg/ kgBW) replacing cyclosporin
      A were given during 7 d after transplantation to 20 patients in 1992 and 30
      patients in 1993, respectively. Numbers of mismatches, combined kidney-pancreas
      transplantation and severe infections were not different for the two groups.
      However, prednisone pulse therapies and additional antilymphocyte globulin
      treatments were more frequent after ATGAM than after ATG induction (p < 0.01, chi
      2-test).

PMID- 8884114
TI  - Prophylactic wound antibiotics for combined kidney and pancreas transplants.
AB  - For combined kidney and pancreas transplant recipients infectious complications
      remain a major source of morbidity. With as many antibiotic protocols as
      transplant centers, the exact type and duration for prophylactic wound
      antibiotics remains undefined. A retrospective review of our series of 40
      combined kidney and pancreas transplants was performed using a single 1 g dose of
      cefazolin preoperatively along with cefazolin bladder and intra-abdominal
      irrigation. Two patients developed superficial wound infections for a rate of 5%
      (2/37). The deep wound infection rate was 11% (4/37), and all followed either a
      bladder anastomotic leak or the initial development of transplant pancreatitis.
      Our overall rate of 16% is very comparable with other series of combined kidney
      and pancreas transplant recipients. To help eliminate the potential development
      of superinfections and resistant organisms, a single dose of antibiotics appears
      to be as effective for wound prophylaxis in these patients when compared to
      multiple-antibiotic and multiple-day regiments. A randomized prospective study of
      prophylactic antibiotics in combined kidney and pancreas transplants is needed.

PMID- 8884115
TI  - OKT3 escalating dose regimens provide effective therapy for renal allograft
      rejection.
AB  - Dose-response relationships for anti-CD3 monoclonal antibody (mAb) therapy remain
      undefined, particularly with respect to higher dose ranges. The clinical efficacy
      and safety of an OKT3 dosing regimen that incorporates higher doses (escalating
      dose regimens) was examined in a pilot trial. Patients undergoing acute rejection
      were treated with a 7-d course of OKT3 in which the daily OKT3 dose was escalated
      during treatment course (daily doses 5, 5, 5, 5, 10, 15, 25 mg). The total amount
      of OKT3 given was equal to a standard 14-d course (70 mg). A total of 10 primary
      cadaveric renal transplant recipients were treated, and data analyzed from a
      median follow up of 5 months (range 3-13 months). Pre-OKT3 immunosuppressive
      therapy consisted of ATGAM induction therapy (n = 8), and corticosteroid
      rejection therapy (n = 6, 18.6 +/- 11.4 mg/kg). Median time of first rejection
      was 32 d (12-48 d) and median time to OKT3 was 33 d (range 15-42 d). Pre-OKT3
      histology (by Banff criteria) included: mild ACR (n = 6), moderate ACR (n = 2),
      AVR (n = 1), ACR and acute transplant glomerulopathy (n = 1). Rejection reversal
      rate with escalating dose OKT3 was 100%, and each patient experienced a rapid
      reversal of rejection (i.e. reversal within 14 d initiation of OKT3 therapy). Six
      recurrent rejection episodes were diagnosed in 5 patients with a median time to
      recurrent rejection of 30 d following cessation of OKT3 therapy. All recurrent
      rejection episodes were successfully treated (FK 506 n = 4, corticosteroids n =
      1, and OKT3 n = 1). CMV disease was limited to a single episode of CMV viremia in
      one patient. PTLD was observed in one patient who had coexisting vascular
      rejection at the time of PTLD diagnosis. Short- and long-term graft function is
      excellent (pre-rejection baseline creatinine 1.8 +/- 0.4 mg/dl, current
      creatinine 1.75 +/- 0.4 mg/dl). Monitoring of OKT3 serum levels revealed that
      patients maintained therapeutic serum levels for an average of 4 d following the
      last OKT3 dose. Circulating CD3+ and CD5+ cells were maintained below baseline
      levels for at least 10 d following the last OKT3 dose. Anti-OKT3 antibody
      formation occurred in 22% of patients, however, anti-idiotypic responses were of
      low titer. Adverse reactions experienced during dose escalation were minimal
      compared to first dose reactions, and consisted primarily of mild headaches and
      arthralgias in a minority of patients. OKT3 EDR, by obviating monitoring and
      administration costs, are cost effective [OKT3 EDR $8088, OKT3 SDR (10 d) $9684,
      OKT3 SDR (14 d) $13,224]. In conclusion, escalating dose regimens of OKT3: 1)
      provide rejection reversal rates similar to standard dose regimens, 2) provide
      high OKT3 serum levels and reliable CD3+ cell depletion, 3) induce minimal
      adverse reactions during dose escalation, and 4) may decrease costs by obviating
      the need for monitoring peripheral blood T cells and by decreasing administration
      costs and outpatient visits.

PMID- 8884116
TI  - The changing nature of neonatal ethics in practice.
AB  - This article overviews the current practice of neonatal care ethics. Tracing the
      evolving nature of neonatal care over the last few decades, the author reviews
      Rhoden's categories of approaches to neonatal care and raises questions about the
      nature of responsibility in neonatal decision making. The role of the parent or
      guardian and the importance of communication is explored. Current neonatal
      outcome studies are reviewed in considering what "best interests" means for the
      newborn. The article concludes by reviewing several issues raised by current
      court cases that may point to the future of ethical decision making in neonatal
      care.

PMID- 8884117
TI  - Organization and function of a hospital ethics committee.
AB  - The developing ethics committee must address many issues around the structure and
      function of the committee. This article reviews such matters as membership,
      training, and committee policy. Committee functions are reviewed with suggestions
      about education as well as ethics consultation.

PMID- 8884118
TI  - Ethical issues surrounding multifetal pregnancy reduction and selective
      termination.
AB  - MFPR and selective terminations satisfy the criteria of enabling pregnancies to
      continue with the least harm and most benefits to all involved. The surviving
      infants can be saved from certain death (abortion) or higher risks of severe harm
      and death and of an extended stay in neonatal intensive care (premature
      delivery). In the hands of trained operators, MFPR and selective termination is,
      in our opinion, the best means to protect the mother's health and well-being,
      given it is available and approved by the parents. MFPR and selective termination
      avoid the trauma of abortion of a wanted pregnancy, enable the parents to achieve
      the goal of having their own child, and avoid the dangers of delivery of multiple
      premature infants. There is no doubt that any procedure that involves the death
      of a fetus will be hotly argued despite the potential for greater good. We
      acknowledge that it will be impossible to convince those who cannot morally
      accept the taking of any life regardless of the circumstances. We hope, however,
      that we have shown there is a place for MFPR and selective termination in a very
      limited number of circumstances and the ethical probity of MFPR and selective
      termination as an option in such cases.

PMID- 8884119
TI  - Management of the pregnant woman who sustains severe brain damage.
AB  - Management of the severely brain-injured pregnant patient is a considerable
      challenge to the ethicist as well as to the obstetrician; to the neurologist;
      and, of course, to any family on which such a tragedy might fall. Certainly, it
      is ethical in some situations to continue somatic support of a lethally injured
      gravida for the benefit of the fetus. It is equally ethical in certain situations
      to withdraw support of a severely neurologically compromised patient regardless
      of an ongoing pregnancy. Physicians caring for such a patient must clarify the
      maternal diagnosis, the fetal gestational age, and the prognosis of both maternal
      and fetal patients. The appropriate proxy decision maker for the patient
      incapable of giving informed consent must be identified, and extensive effort
      must be expended to educate and empathize with that individual as well as any
      other involved family members. Application of the basic principles of medical
      ethics can then provide a framework within which the above information can be
      used to develop and evolve an appropriate clinical management plan for the
      specific situation at hand.

PMID- 8884120
TI  - Congenital diaphragmatic hernia. In utero therapy and ethical considerations.
AB  - Despite advances in neonatal medicine, the mortality rate for congenital
      diaphragmatic hernia remains high. The results of work in animal models suggest
      that this anomaly may be amenable to in utero surgical correction. In this
      article, the natural history of congenital diaphragmatic hernia in humans is
      reviewed, and the development of antenatal management strategies is traced. The
      ethical issues surrounding the management of fetuses with diaphragmatic hernias
      are also discussed. The ground-breaking nature of the development of strategies
      for management of congenital diaphragmatic hernia underscores the importance of
      establishing scientific and ethical guidelines for future endeavors with in utero
      therapy.

PMID- 8884121
TI  - From how small is too small to how much is too much. Ethical issues at the limits
      of neonatal viability.
AB  - In recent years, survival of the extremely low birthweight infant has
      dramatically improved. Morbidity, both short- and long-term, however, remains
      very high Costs in the currency of pain and suffering for the newborn, stress and
      financial burdens for the family, and dollars for society are extensive. The
      controversial questions that are discussed include: How small is too small? How
      much is too much? How far should we go? How much can we afford? Who should
      decide? What strategies should be followed to ensure such decisions are just?

PMID- 8884122
TI  - Toxicology testing in neonates. Is it ethical, and what does it mean?
AB  - A positive toxicology screen in a newborn may provide some explanation for signs
      and symptoms affecting the newborn's problems in the NICU. But, simply stated, it
      does not prove cause; it does not prove child neglect; it does not prove
      inadequate parenting capabilities. The evidence of maternal illicit substance use
      may provide us with information that a variety of risk factors associated with
      drug use may be interacting that could interfere with the infant's long-term well
      being. The objective of screening must be focused on medical and health care
      issues, not on political or legal issues, and never intended for punitive actions
      toward the mother. Resources should be available to provide the mother with
      educational information, treatment programs, psychosocial counseling, and
      household support systems to assist her in her role as principal caregiver to her
      infant. Follow-up care for the baby should be provided by physicians and clinics
      familiar with high-risk infants and include ongoing neurodevelopmental
      surveillance in specialized programs if available.

PMID- 8884123
TI  - Ethical decision making in perinatal asphyxia.
AB  - This article examines the difficulties of defining perinatal asphyxia. Once the
      central clinical concern is identified, the ethical questions become clearer. A
      variety of procedural and ethical issues also need to be considered; especially
      those related to how physicians introduce and dialogue with parents about
      difficult life and death decisions. Depending on how well this is accomplished,
      sound medical practice, parental autonomy and the patient's best interest issues
      can all be effectively addressed with a minimum of conflict.

PMID- 8884124
TI  - The safe introduction of new technologies into neonatal medicine.
AB  - In neonatal medicine, there is a technologic revolution in progress. During the
      past 10 years, we witnessed the introduction and improvement of monitoring
      equipment, the development of new modes of assisted ventilation, and the
      proliferation of extracorporeal membrane oxygenation. This article reviews how we
      might improve the process of the safe introduction of new technologies into
      neonatal medicine.

PMID- 8884125
TI  - Ethical decisions in the delivery room.
AB  - Avoidance of futile therapies that only prolong suffering and the high emotional
      and economic cost to family and society justifies an attempted differentiation of
      infants whose defects are so extensive or whose prognoses are so poor that CPR
      should be withheld. This article discusses the ethical bases for decision making
      in the DR and the three most common diagnoses in which CPR decisions are most
      difficult: infants with severe congenital defects, extremely low birthweight
      infants, and infants with severe perinatal asphyxia.

PMID- 8884126
TI  - Can and should level II nurseries care for newborns who require mechanical
      ventilation?
AB  - Perinatal regionalization was conceived roughly 25 years ago to provide
      centralized care for critically ill newborn infants. As for many 25-year-old
      concepts, the obligatory centripetal design of many regionalization policies may
      need to be modified. This article presents the outcomes of 408 surviving patients
      who required mechanical ventilation (136 born in one community hospital and 272
      birthweight-matched infants born in our tertiary center), and were cared for in
      our perinatal network. Mechanical ventilation of a resident population of
      newborns at a community NICU appeared to be as effective as ventilatory care at a
      regionalized tertiary neonatal intensive care unit, when assessed by comparing
      birthweight-matched populations for length of hospital stay, days on ventilator,
      and the need for home O2. Some may still claim that every baby who requires
      mechanical ventilation must be transferred to a tertiary care center. In an era
      of heightened interest in health services, health outcomes, and cost
      effectiveness analysis, however, the authors believe that such claims will be
      subjected to increasing scrutiny. Our study represents a first attempt at
      determining the shape such scrutiny might take, and the sort of data analyses
      that may be required to reformat a perinatal network.

PMID- 8884127
TI  - Physicians' refusal to provide life-prolonging medical interventions.
AB  - The intense and ongoing debate on physicians' right to refuse requested life
      prolonging medical interventions highlights one of the emerging problems in
      modern medicine: the limits, if any, to a patient (or proxy's) claim to requested
      treatment. How is the physician to respond to requests for treatment believed by
      the physician to be futile, ineffective, or inappropriate? Three cases, Baby L,
      the extracorporeal membrane oxygenation (ECMO) baby, and Baby K, help focus the
      ethical and legal issues in this debate.

PMID- 8884128
TI  - Parental discretion in refusal of treatment for newborns. A real but limited
      right.
AB  - Manslaughter charges were brought in Lansing, Michigan against Gregory Messenger,
      a local dermatologist, for removing his extremely premature infant son from a
      ventilator in a neonatal intensive care unit. The issue in the case was the
      degree of intervention required for the newborn for whom the parents had been
      counseled that there was a 50% to 70% mortality and that if the child did
      survive, there was a 20% to 40% chance of severe intraventricular hemorrhage and
      a likelihood of substantial respiratory problems. In light of those grim data,
      the parents requested that no aggressive measures be undertaken. The
      neonatologist instructed her physician's assistant to ventilate if the child was
      "vigorous." The homicide charge was based on Gregory Messenger's failure to
      provide proper medical treatment for his infant son.

PMID- 8884129
TI  - Expert testimony, legal reasoning, and justice. The case for adopting a data
      based standard of care in allegations of medical negligence in the NICU.
AB  - Sunstein has written, "First, and most obviously, judgments about specific cases
      must be made consistent with one another. A requirement of coherence, or
      principled consistency, is a hallmark of analogic reasoning (as it is of
      reasoning of almost all sorts)." In cases of alleged medical negligence, our
      current system of malpractice litigation supports the possibility that inaccurate
      anecdotal testimony by expert witnesses may be credited equally or even preferred
      to more accurate testimony based on empiric data. This condition lends itself to
      inconsistent outcomes that violate basic principles of justice. In our view, the
      standard of medical care ought not be described by the idiosyncratic postulation
      of single behavior (analogous to promulgating the equation of a single line on a
      Cartesian plane). Rather, the standard of medical care is best viewed as a
      distribution of behaviors (family of lines) that can be empirically determined to
      account for most practice decisions in comparable cases. The recent Daubert
      formulation of admissibility of expert testimony can be interpreted as providing
      judicial support for a hierarchy of expert testimony in cases of alleged medical
      negligence. On this view, testable comparisons of the behavior in question
      against reliably documented distributions of standard medical behavior in similar
      circumstances rank higher than untestable comparisons using unreliable anecdotal
      recollections of individual expert's undocumented experience. We believe that
      widespread adoption by the medical community of the principle that the value of
      expert testimony describing the standard of medical care increases in direct
      proportion to its congruence with a data-based determination of the distribution
      of skill and care ordinarily provided in similar circumstances would
      significantly reduce the potential for injustice visited on plaintiff and
      defendant alike.

PMID- 8884131
TI  - The socially complex family. New dilemmas for the neonatal social worker.
AB  - The multifaceted problems of many families now cared for in neonatal units place
      new challenges on the neonatal social worker. The medical complexities of the
      NICU patient are matched by the social complexities of many of the families. The
      worker attempts to coordinate multiple systems to meet the need of the infant and
      family throughout the hospitalization of the infant. The advances in medical
      technology, however, have not been matched in the social and support systems. The
      result is the creation of new dilemmas for the worker, the medical staff, and
      society.

PMID- 8884130
TI  - Distributive justice across generations. Epidemiology of ICU care for the very
      young and the very old.
AB  - Babies of extremely low birthweight and elderly adults both require expensive and
      scarce resources, and both have a relatively poor prognosis for survival if they
      require intensive care. Thus, proposals for rationing often target one or both of
      these groups. We suspected that although mortality rates might be higher in the
      neonatal intensive care unit (NICU) than in the adult intensive care unit (ICU),
      NICU care might nevertheless be more cost effective, where cost efficiency is
      measured along the dimension of resources targeted to survivors. We examined
      mortality patterns in our NICU and for adults admitted to our medical intensive
      care units. We found that adult ICU patients who died consumed many times more
      ICU resources before their death than did their NICU confreres, independent of
      the severity of illness or likelihood of dying. Although there may be many
      legitimate concerns about justice and ethics in the NICU, undue expenditure of
      society's resources prolonging the dying of extremely low birthweight infants is
      not among them. To the extent that concerns about distributive justice drive
      allocation decisions in ICU care, it would seem more justifiable to ration
      intensive care for the very old, not the very young.

PMID- 8884132
TI  - Monitoring of neuromuscular transmission by electromyography during anaesthesia.
      A comparison with mechanomyography in cat and man.
AB  - In this study the applicability of the electromyographical method for monitoring
      neuromuscular transmission during anaesthesia has been investigated. The purpose
      was to determine the stability and temperature dependence of the EMG and to
      evaluate and compare EMG area, amplitude and duration during a non-depolarizing
      neuromuscular block in the tibialis anterior muscle preparation of the cat.
      Further, in clinical studies the purpose was to investigate differential hand
      muscle sensitivity to non-depolarizing neuromuscular blocking agents based on the
      EMG and the standard adductor pollicis mechanomyogram, and to establish the
      agreement between the electromyographical and the mechanomyographical methods and
      their relationship to clinical parameters of residual neuromuscular block. For
      this purpose a new monitoring equipment was developed for simultaneous recording
      of the evoked mechanomyogram and the surface compound EMG area, amplitude and
      duration. In the animal studies the EMG was found to be stable with changes less
      than 10% during 3 hours of stimulation and with a high degree of reproducibility.
      In contrast, the mechanomyogram proved unstable over time with changes of 35-50%
      (positive staircase) within minutes after onset of stimulation followed by a
      slower decline of the response to 70-75% of control. An inverse relationship was
      found between temperature and both the mechanomyogram and the EMG, the EMG area
      and duration being more affected (5-7% per degrees C) than EMG amplitude (2-3%
      per degrees C). During onset and recovery from non-depolarizing neuromuscular
      block, EMG area and amplitude of the first major negative deflection and of the
      total compound response both reflected neuromuscular transmission equally. The
      EMG duration was found to be unsuitable as a predictor of neuromuscular block. In
      the clinical studies of the hand muscles (adductor pollicis, hypothenar and first
      dorsal interosseous muscles) small but clinically insignificant differences in
      EMG-based sensitivity to pancuronium were observed. There was no difference
      between EMG area and amplitude in the estimated effective doses of pancuronium
      and roctronium producing 50% and 90% block, respectively (ED50 and ED90), but EMG
      based sensitivity of the adductor pollicis muscle was less than when based on
      mechanomyography. Comparative analysis of first dorsal interosseous EMG and
      adductor pollicis mechanomyogram during non-depolarizing neuromuscular block was
      based on the concept of bias (mean difference between the results by the two
      methods) and limits of agreement (an estimation of how much results obtained with
      one method are likely to differ from the results of the other method) and
      evaluated during TOF nerve stimulation. The two methods agreed within acceptable
      limits during neuromuscular block with estimated bias being less than 2% during
      onset. A variable bias of 3-7% was observed during recovery, with EMG
      overestimating block at 25% recovery and underestimating block at 75% and 90%
      recovery. Limits of agreement were more narrow during onset (+/- 7-8%) than
      during recovery (+/- 12-17%), EMG area and amplitude equally reflected the degree
      of neuromascular block. First dorsal interosseous EMG TOF ratio recovered more
      slowly than TOF ratio of the adductor pollicis mechanomyogram during early
      recovery. The relationship between the two methods was described as being log
      linear, and during late recovery bias between the TOF ratios of the two methods
      was zero. However, due to the range of deviations between the EMG and the
      mechanomyogram, EMG TOF ratios down to 0.55 or up to 0.90 in some patients were
      found to be compatible with adequate recovery of a mechanomyographical TOF ratio
      of 0.75. Differences between electromyographical and mechanomyographical TOF
      ratios in their relation to 5 s sustained headlift were only revealed when the
      TOF ratio was below 0.50-0.60. More patients were then able to perform the test
      if the TOF ratio was measured from the EMG.(ABSTRACT T

PMID- 8884133
TI  - Effects of indomethacin and local prostaglandin E2 on fracture healing in
      rabbits.

PMID- 8884134
TI  - The personality pattern in peptic ulcer disease.

PMID- 8884135
TI  - Cellular heterogeneity in malignant tumors. The importance of clonal interaction
      on tumor evolution, response to chemotherapy and metastatic ability evaluated in
      experimental systems.

PMID- 8884136
TI  - Geriatric work-up in the Nordic countries. The Nordic approach to comprehensive
      geriatric assessment.
AB  - A group established by the Nordic professors of geriatrics has developed a
      position document presenting a shared and updated review of geriatric work-up as
      a way of comprehensive geriatric assessment in the Nordic countries. The main
      intention is that the document will serve as support and help for the clinician
      concerned with hospital based geriatric medicine. It may also be useful for
      quality control and teaching. Not least, it may be useful for health
      professionals other than geriatricians. To some extent, the position of geriatric
      medicine in the Nordic countries varies between the countries. However, the
      background for developing a Nordic version of geriatric work-up is shared
      attitudes and principally the same organization of the health care system, and
      collaboration within geriatrics for many years. Several trials on comprehensive
      geriatric assessment and management performed in different settings have shown
      favourable outcomes. Results from controlled Nordic trials are compiled and
      summaries of meta-analyses are presented. The concept of Nordic geriatric work-up
      is based on a model defining health and disease in old age as dimensions of
      pathology, impairments, functional limitations, and disability, all being
      modified by extra- and intraindividual factors. Handicap is defined as the
      disability gap. Different health professionals have varying responsibilities in
      the geriatric team-work, but all should be dedicated to establish common goals.
      The geriatric work-up is presented with success factors and barriers, stating
      important differences between multidisciplinary and interdisciplinary processes.
      Checklists and assessment scales may be very useful when performing a geriatric
      work-up, but they should be used with caution. Specific scales covering different
      functional areas of the geriatric patient are recommended for clinical practice.
      Such scales must be valid, reliable, acceptable to the patient, responsive to
      change, and should be in an appropriate format, as well as easy to administer.
      Prior to the use among geriatric teams in the Nordic countries the scales should
      be translated into all the Nordic languages, and the translated versions should
      ideally have been subjected to validity and reliability testing. However, so far
      no scale meets these demands regarding all the five Nordic languages.

PMID- 8884137
TI  - Long-lasting functional abdominal pain and duodenal ulcer are associated with
      stress, vulnerability and symptoms of psychological stress. A controlled study
      including healthy and patient controls.
AB  - OBJECTIVE: To assess psychological differences between patients with functional
      abdominal pain (FUNC) and three separate control groups comprising patients with
      duodenal ulcer (DU), patients with gallstone or urinary tract stone (STONE), and
      healthy non-patient controls (HEALTH). METHODS: All participants completed a self
      administered questionnaire including questions about the relationship between
      symptoms and certain life events and psychometric tests for psychological
      distress (SCL-90) and vulnerability. PARTICIPANTS: The FUNC group consisted of 27
      hospital outpatients with long-lasting abdominal pain without demonstrable
      abnormalities (ten men and 17 women; mean age 38 years). The DU group consisted
      of 13 untreated outpatients with endoscopically proven duodenal ulcer (nine men
      and four women; mean age 42 years) while the STONE group comprised 13 untreated
      patients with gallstone (n = 7) or urinary calculi (n = 6) (six men and seven
      women; mean age 43 years). The HEALTH group consisted of five men and nine women
      (mean age 36 years). RESULTS: Significantly more FUNC and DU patients compared
      with STONE patients experienced an association with at least one of 14 life
      events (74%, 77%, and 31%, respectively; p = 0.02). The FUNC and DU groups showed
      significantly higher scores on the depression subscale of the SCL-90 than the
      HEALTH group (p < 0.05), and on the anxiety subscale compared with the STONE and
      HEALTH groups (p < 0.05). The FUNC group scored significantly higher on the
      somatization subscale compared with all the other groups (p < 0.05). As an
      overall measure of psychological distress the Global Severity Index (GSI) was
      calculated. GSI was significantly higher in the FUNC group compared with the
      HEALTH group (p < 0.01) and tended to be higher in the DU group (p = 0.06). The
      FUNC and DU groups had significantly higher scores for vulnerability than the
      STONE and HEALTH groups (p < 0.05). CONCLUSION: FUNC as well as DU outpatients
      seem to be more psychologically distressed and vulnerable than healthy controls
      or outpatients suffering from pain caused by stones in the gallbladder or urinary
      tract. As opposed to the STONE group, a high proportion of the FUNC and DU
      patients experienced that the onset or aggravation of abdominal pain was
      associated with certain life events. The similarities between the FUNC and DU
      group demonstrate that it is important to separate DU patients from other
      "organic" patients in such investigations.

PMID- 8884138
TI  - Juvenile avascular necrosis of the odontoid process. A review on the etiology of
      os odontoideum and absentia odontoidei.
AB  - Os odontoideum (OO) and absentia odontoidei (AO) are rare conditions, which
      mainly are of interest because they may cause atlanto-axial instability.
      Traditionally they are considered to be congenital lesions. However, during the
      latest decades a number of acquired cases have been reported. Presently it is
      generally believed that the two conditions may exist in both a congenital and an
      acquired version. A review of the literature about OO fails to disclose any solid
      evidence in support of the classical theory of congenitality. It is concluded
      that OO and AO are diseases of childhood and adolescence. They are probably
      always acquired, and result from avascular necrosis of the odontoid process
      during the growth process.

PMID- 8884139
TI  - Update on Sjogren-Larsson syndrome.
AB  - Sjogren-Larsson syndrome (SLS, MIM 270200) is a rare autosomal recessive
      neurocutaneous disorder due to a deficiency of the fatty aldehyde dehydrogenase
      and defined by a characteristic triad of symptoms including congenital
      ichthyosis, spastic di- or quadriplegia and mental retardation. Recently, genetic
      studies have subsequently shown linkage of the syndrome to chromosome 17p in
      Swedish pedigrees, confirmation of linkage to the same locus in non-Swedish
      pedigrees, and finally cloning of the gene as well as detection of mutations in
      affected probands. Furthermore, SLS may well be soon added to the list of
      peroxisomal disorders. The purpose of this paper is to provide an up-to-date
      synopsis of SLS and to outline specific aspects of this syndrome that are still
      unclear.

PMID- 8884140
TI  - Staphylococcus aureus skin colonization in infants with atopic dermatitis.
AB  - BACKGROUND: Coagulase-positive Staphylococcus aureus colonizes eczematous lesions
      in 78-100% of children and adults with atopic dermatitis (AD), whereas it is
      found on skin of healthy subjects in only 2-25% of cases. On unaffected skin of
      subjects with AD the bacterium has been isolated in 51-100% of cases. OBJECTIVE
      AND METHODS: This paper examines rate and density of S. aureus colonization,
      using the swab technique and the contact plate method, respectively, on affected
      and unaffected skin in 72 infants with AD (age 3-24 months) and in a control
      group, to determine if there are significant differences with respect to what is
      reported for children and adults with AD. RESULTS AND CONCLUSIONS: The main
      differences is that on unaffected skin of our infants with AD, bacterium
      colonization rate is significantly lower than on affected skin.

PMID- 8884141
TI  - Amicrobial pustular dermatosis of cutaneous folds associated with autoimmune
      disorders: a new entity?
AB  - BACKGROUND: An unclassified amicrobial pustular dermatosis particularly affecting
      the main cutaneous folds, external auditory canals and scalp and coexisting with
      systemic lupus erythematosus has been recently described. OBJECTIVE: We studied 3
      young females bearing such cutaneous manifestations in association with subacute
      cutaneous lupus erythematosus, celiac disease and various serum autoantibodies,
      respectively, in order to further characterize this possibly new entity. METHODS:
      Various routine and immunological laboratory tests, histopathologic and direct
      immunofluorescence examinations and in vitro studies of neutrophil function were
      performed in each patient. RESULTS: We reported our findings and compared our
      cases with the few others appearing in the literature. We documented an impaired
      neutrophil chemotaxis in 2 subjects, but neutrophil dysfunction does not seem to
      be one of the verifying criteria. CONCLUSIONS: All of these cases may represent a
      distinctive form in the clinicopathological spectrum of neutrophilic dermatoses
      (ND) because of the typical distribution and the close link with different
      autoimmune disorders. Cimetidine in combination with ascorbic acid can be
      indicated as an effective and safe alternative to the classic medications of ND,
      although the action of both drugs remains unexplained.

PMID- 8884142
TI  - Urticarial pathology in Schnitzler's (hyper-IgM) syndrome.
AB  - BACKGROUND: Schnitzler's syndrome is a rare disorder characterized by chronic
      urticaria and monoclonal IgM gammopathy. The mechanisms of the urticarial flares
      remain poorly understood. OBJECTIVE: To more accurately define the
      histopathologic changes in urticarial lesions, we reviewed 25 original biopsies
      from 15 cases of Schnitzler's syndrome, 11 of which have previously been
      reported. RESULTS: Thirteen specimens from 9 patients showed urticaria with
      neutrophils (neutrophilic urticaria). Necrotizing leukocytoclastic vasculitis
      with positive immunofluorescence studies was found only in 2 biopsies from 1
      patient who was genetically deficient in C4. Five specimens showed lymphocytic
      urticaria. Four biopsies demonstrated a spongiotic dermatitis; an eosinophilic
      spongiosis was seen in 2 biopsies from a patient who later developed pemphigus
      vulgaris. Epidermal changes were seen in 17 specimens from 10 patients.
      CONCLUSIONS: The histopathologic findings in Schnitzler's syndrome are not
      uniform although most cases demonstrated neutrophilic urticaria. Neutrophils in
      Schnitzler's syndrome are not usually related to immune complex vasculitis.
      Epidermal changes in Schnitzler's syndrome need to be further analyzed.

PMID- 8884143
TI  - Kaposi's sarcoma after liver transplantation.
AB  - BACKGROUND: Kaposi's sarcoma (KS), is a known complication following kidney
      transplantation. It has been reported more rarely following liver
      transplantation. OBJECTIVE: To assess the clinico-epidemiologic data of KS after
      liver transplantation. METHODS: 150 liver graft recipients were examined; those
      presenting with KS were studied clinically, histologically and virologically.
      RESULTS: Three cases of KS were observed. The three patients had been treated
      with OKT3 antiserum in addition to the standard regimen. The delay of appearance
      varied from 5 to 36 months. Two patients had a few cutaneous lesions and 1 had
      more extensive involvement; none of them had visceral localizations. In 2 cases,
      herpesvirus-like DNA sequences were detected within the lesions. Therapy
      consisted in decreasing the immunosuppressive treatment, in association with
      alpha-interferon or vindesine in 2 cases, respectively. All patients were alive
      after a follow-up of 19-45 months. CONCLUSION: KS seems relatively frequent (2%)
      and appears within a short delay after liver transplantation; the prognosis may
      be more favourable than previously reported.

PMID- 8884144
TI  - Prognostic value of tuberculin and BCG immunoreactivity in stage I high-risk
      malignant melanoma (EORTC protocol 18781).
AB  - BACKGROUND: Since the immune system is considered to be a major determinant in
      the outcome of malignant melanoma, vaccination with BCG (bacillus Calmette
      Guerin) or more recently with interleukins is used in this condition, although
      the effects of this immunotherapy are unclear. OBJECTIVE: The present study was
      to elucidate clinical aspects and the prognostic relevance of the cellular and
      humoral immune responses of melanoma patients treated with two different BCG
      vaccines. METHODS: A subgroup of patients from a multicenter adjuvant trial with
      BCG in stage I (pT3-4N0M0) high-risk melanoma was prospectively subjected to
      detailed analysis regarding tuberculin (PPD, purified protein derivate) skin test
      reactivity, local, regional and systemic reactions to BCG vaccination, PPD
      antibody response and disease-free survival. Patients were randomized into three
      arms and received either no adjuvant treatment (22 patients), BCG RIV (40
      patients) or BCG Pasteur (44 patients). All patients were followed for up to 10
      years (median follow-up 6 years). RESULTS: Patients treated with BCG Pasteur
      mounted a stronger antibody response, experienced stronger regional and systemic
      reactions to vaccination and converted more frequently to positive PPD skin
      tests, compared to controls and to patients vaccinated with BCG RIV. All BCG
      treated patients who developed an antibody response had a longer disease-free
      interval (p = 0.05), with slightly higher significance for BCG Pasteur-treated
      patients (p = 0.02). CONCLUSIONS: Cellular as well as humoral immune responses to
      PPD and BCG thus identify stage I malignant melanoma patients with an overall
      better prognosis.

PMID- 8884145
TI  - Immunolocalization of human gelatinase (type IV collagenase, MMP-9) and tissue
      inhibitor of metalloproteinase 1 in Hailey-Hailey and Darier's diseases.
AB  - BACKGROUND: The formation of lacunae and acantholysis as well as dyskeratosis are
      characteristic features of Hailey-Hailey disease (HHD) and Darier's disease (DD).
      Matrix metalloproteinases (MMPs) and their inhibitors like tissue inhibitors of
      metalloproteinases (TIMPs) have been thought to play major roles in the tissue
      metabolism. OBJECTIVE: The aim of this study was to investigate the role of MMP-9
      and TIMP-1 in HHD and DD. METHODS: We examined localizations of these two
      molecules by immunostaining using specific monoclonal antibodies. RESULTS: MMP-9
      was positively stained in dyskeratotic or detaching cells around lacunae in HHD
      and DD. TIMP-1 showed a positive staining pattern throughout the epidermis.
      CONCLUSION: MMP-9 might be involved in the pathophysiological process of HHD and
      DD in the presence of TIMP-1.

PMID- 8884146
TI  - Evening primrose oil (Epogam) in the treatment of chronic hand dermatitis:
      disappointing therapeutic results.
AB  - BACKGROUND: Hand dermatitis is a common therapeutic challenge with limited and
      unsatisfactory therapy modules. A possible beneficial role of oral evening
      primrose oil needs to be investigated. OBJECTIVE: Pharmacological doses of gamma
      linolenic acid (GLA) could improve the water permeability barrier of the
      epidermis in chronic hand dermatitis. Clinical improvement, changes in the
      lipogram and epidermal lipid composition could define functional improvement of
      the skin. Electron-microscopic evaluation of the epidermal lipid bilayer could
      underline the efficacy of essential fatty acids in chronic hand dermatitis.
      METHODS: Thirty-nine patients with chronic (> 1 year), stable hand dermatitis
      entered a 24-week double-blind placebo-controlled trial. Patch test with the
      European standard of allergens, haematogram and serum IgE values were determined
      before commencement of the study. Active therapy (600 mg/day of GLA) was
      administered to half the patient group. Medication was given for 16 weeks and
      observations continued for another 8 weeks. Patients were assessed clinically,
      using a visual analogue scale at 4-week intervals. Plasma and red blood cell
      lipograms, as well as skin biopsies, were taken before therapy, after the 16-week
      supplementation period and at week 24. Tissue was used for histological
      evaluation, electron-microscopic assessment and epidermal lipid analysis.
      RESULTS: Improvement in clinical parameters was present in the Epogam and placebo
      groups, but no statistical difference could be confirmed between the groups.
      Haematogram, blood and epidermal biochemistry were normal at baseline. No change
      in the lipid composition of plasma red cells or epidermis could be detected
      during the trail. Ultrastructurally skin specimens showed no change during the
      study period. CONCLUSION: The study indicates that the therapeutic value of
      orally administered GLA for chronic hand dermatitis is not superior to that of
      placebo.

PMID- 8884147
TI  - Tachyphylaxis to histamine-induced wheal suppression by topical 0.05% clobetasol
      propionate in normal versus croton oil-induced dermatitic skin.
AB  - BACKGROUND: Patients often tell about reduced effectiveness of topical steroids
      on repeated use. Tachyphylaxis to these agents has been demonstrated in humans
      for vasoconstriction and histamine-induced wheal suppression in normal skin, but
      not in diseased skin. Relevance of these data to diseased skin is not clear.
      Further, the clinical impression does not appear to match tachyphylaxis shown in
      normal skin with regard to the time course. OBJECTIVES: To examine whether
      tachyphylaxis to histamine-induced wheal suppression by a topical steroid occurs
      in dermatitic skin and to determine its time course vis-a-vis normal skin.
      METHODS: Pharmacodynamic response to 0.05% clobetasol propionate applied daily
      under occlusion was measured by histamine-induced wheal suppression assay in 10
      individuals. This test was performed on a steroid-treated normal site, on a
      steroid-treated site where dermatitis was induced by occlusive application of 40%
      croton oil, and on a vehicle-treated site in each individual at different
      intervals up to 14 days. RESULTS: Suppression of wheal volume started from second
      day in steroid-treated sites. There was significant difference in the wheal
      volume in steroid treated normal vs. dermatitic sites from day 2 to day 10.
      Maximum wheal suppression occurred earlier in dermatitic skin (day 4 vs. day 6).
      After this, the volume of wheal started increasing and became equal to control
      (complete tolerance) on 12th day in dermatitic skin and on 14th day in normal
      skin. CONCLUSIONS: Time courses of tachyphylaxis to the action of 0.05%
      clobetasol propionate were significantly different in normal skin and dermatitic
      skin. Complete tolerance occurred earlier in dermatitic skin compared to normal
      skin.

PMID- 8884148
TI  - Oral 9-cis-retinoic acid versus 13-cis-retinoic acid in acne therapy.
AB  - BACKGROUND: 9-cis-Retinoic acid (9-cis-RA) is as active as 13-cis-retinoic acid
      (13-cis-RA) in inhibiting the proliferation of cultured human sebocytes and in
      reducing the size of sebaceous glands of hamsters. OBJECTIVE: Evaluate the anti
      acne effect of 9-cis-RA compared to that of 13-cis-RA in a pilot study. METHODS:
      Four young male patients with acne were treated in an open study consecutively
      with 9-cis-RA and 13-cis-RA given at similar doses. RESULTS: No beneficial
      effects were observed with 9-cis-RA in any of the patients whereas all responded
      favorably to 13-cis-RA. CONCLUSION: For the two retinoids tested, the anti-acne
      effect correlates with the sebosuppressive effect in humans.

PMID- 8884149
TI  - Sebum excretion rate in subjects treated with oral all-trans-retinoic acid.
AB  - BACKGROUND AND OBJECTIVE: It is generally accepted that the inhibition of sebum
      excretion has a predictive value for anti-acne activity. Whereas oral 13
      cisretinoic acid (13-cis-RA) decreases sebum excretion, it has not been shown so
      far if oral all-trans-retinoic acid (tretinoin, tRA) does so. The aim of this
      exploratory study was to investigate the effect of oral tRA on the sebum
      excretion rate (SER) in young male subjects. METHODS: 12 healthy volunteers with
      a baseline SER above 1.0 microgram/cm2/min were treated with 20 mg/day tRA for 4
      weeks. The SER was measured at weeks 2 and 4. Adverse reactions were recorded.
      RESULTS: The mean SER varied from 1.56 at baseline to 1.65 at week 2 and to 1.49
      micrograms/cm2/min at week 4. Comparison with values obtained in the same
      subjects previously treated with either 13-cis-RA or 9-cis-retinoic acid
      indicated that tRA less sebosuppressive. Mucocutaneous reactions and headache
      were the most frequent side effects of oral tRA. CONCLUSION: The lack of effect
      on the SER suggests that oral tRA would probably be ineffective against acne. The
      fact that, of the three isomers tested, only 13-cis-RA (which does not bind to
      nuclear receptors) shows activity may suggest that sebosuppression is not nuclear
      receptor mediated. We discuss other hypotheses related to pharmacokinetics.

PMID- 8884150
TI  - Papuloerythroderma of Ofuji: a report of 2 cases including the first European
      case associated with visceral carcinoma.
AB  - Papuloerythroderma (PE) is a rare type of erythroderma of the elderly which
      results from the coalescence of sheets of papules that spare skin folds, with
      peripheral eosinophilia in most cases. Skin biopsy shows a nonspecific eczematous
      pattern with a mature T cell lymphocytic and eosinophilic infiltrate with
      Langerhans cells in the dermis. We report 2 cases of PE. The 1st case, in which
      no underlying malignancy could be found, responded partially to oral etretinate,
      topical steroid creams and tar derivates. The 2nd case did not respond to high
      dose oral steroids and was associated with adenocarcinoma of the colon, with a
      fatal outcome. PE has been associated with lymphoma and carcinoma. We report the
      first European case of PE associated with visceral carcinoma and review the cases
      reported in the western literature.

PMID- 8884151
TI  - Squamous cell carcinoma arising in a verrucous epidermal nevus.
AB  - A 74-year-old Japanese male patient with squamous cell carcinoma arising in an
      epidermal nevus is described. The patient had widespread warty lesions involving
      large parts of the body since infancy. Recently, a nodular lesion appeared on the
      middle part of his back and increased in size. Histologically, the nodule was
      diagnosed as squamous cell carcinoma and the warty lesion showed the features of
      epidermal nevus. The nodular lesion was totally excised and the skin defect was
      covered with split-thickness skin grafting. To the best of our knowledge, this is
      the 16th patient with malignant change of a verrucous epidermal nevus.

PMID- 8884152
TI  - Porokeratotic eccrine ostial and dermal duct nevus of late onset: more frequent
      than previously suggested?
AB  - We describe the case of a 10-year-old boy with a porokeratotic eccrine ostial and
      dermal duct nevus (PEODDN) of late onset. The patient had an 8-year history of
      multiple keratotic papules on the dorsal surface, and multiple yellowish pitting
      lesions on the plantar surface of the right foot. Light-microscopic studies of
      both lesions showed multiple cornoid lamella-like parakeratotic columns, which
      exclusively arose over eccrine sweat ducts in which the acrosyringium was
      dilated. Although PEODDN is considered to be a congenital hamartoma of eccrine
      origin, a review of the literature showed us that the frequency of a late-onset
      variant may be as high as 26%.

PMID- 8884153
TI  - Characteristic but unfamiliar--the cowpox infection, transmitted by a domestic
      cat.
AB  - An 11-year-old girl had been suffering from 2 recently developed reddish
      ulcerated nodules on the right side of her neck and, concomitantly, from a very
      hard swelling as well as from painless lymphadenopathy. Subsequently, thick black
      eschars appeared on the surface of the ulcers. Using the negative staining
      technique, an orthopox virus infection could be identified by electron
      microscopy. The patient's characteristic history as well as her close contact
      with a cat frequently hunting nice indicated the diagnosis of a cowpox infection,
      which was unequivocally confirmed by identification of both the viral culture and
      specific antibodies in the serum of the patient.

PMID- 8884154
TI  - Sarcoidosis presenting as a scarring alopecia: report of a rare cutaneous
      manifestation of systemic sarcoidosis.
AB  - We report a 51-year-old woman with alopecia caused by sarcoidosis. The lesion
      enlarged within 4 years and only repeated biopsies enabled the diagnosis. The
      medical work-up revealed that the patient had asymptomatic pulmonary involvement.
      Scarring alopecia is a rare complication of sarcoidosis and biopsy from the
      active margin may lead to the diagnosis.

PMID- 8884155
TI  - Palmar papillomatous lesions reminiscent of epidermal nevus in a case of focal
      dermal hypoplasia: a nosological consideration.
AB  - A 40-year-old woman with focal dermal hypoplasia had a palmar papillomatous
      lesion showing a linear arrangement and histopathological features compatible
      with a diagnosis of epidermal nevus. This unusual manifestation of focal dermal
      hypoplasia is difficult to categorize. Undoubtedly the lesion reflects functional
      X-chromosome mosaicism. Although the mechanism of lyonization may give rise to
      true epidermal nevi such as CHILD nevus, we prefer to classify the present skin
      lesion as a nevoid disorder and not as an epidermal nevus.

PMID- 8884156
TI  - Plantar infection by Scopulariopsis brevicaulis.
AB  - A 42-year-old woman presented with a well-defined pruritic erythematous scaly
      plaque on the sole of each foot. The lesions, first noted about 15 years
      previously, were located in the medial plantar region and extended laterally.
      Mycological study revealed infection by Scopulariopsis brevicaulis. Treatment
      with oral itraconazole led to temporary improvement, but the symptoms returned
      after treatment had been stopped (presumably due to re-infection from ungual
      foci). Similar results were subsequently obtained with oral terbinafine. S.
      brevicaulis is an aetiologic agent of onychomycosis, panophthalmia following a
      penetrating eye injury and generalized infections in immunocompromised patients,
      but it is not considered as habitual fungal pathogen of the skin. Cutaneous
      lesions caused by S. brevicaulis are very rare. Our case was resistant to
      terbinafine and itracomazole.

PMID- 8884157
TI  - Multiple hidrocystomas.
AB  - Apocrine hidrocystoma is a cyst from the secretory portion of the apocrine sweat
      gland and tends to occur as a solitary facial lesion. We report a 66-year-old
      woman with multiple, cystic lesions on her face. Histopathology revealed cystic
      spaces lined by a row of secretory cells showing decapitation secretion. We
      emphasize the multiple character of the case and discuss its distinction from so
      called eccrine hidrocystomas.

PMID- 8884158
TI  - Sweet's syndrome and malignancy: a case associated with multiple oral squamous
      cell carcinoma.

PMID- 8884159
TI  - Measurement of actinic erythema in healthy subjects and in subjects with
      polymorphous light eruption using a tristimulus colorimeter.

PMID- 8884160
TI  - Neurotoxicity of carbapenem antibacterials.
AB  - Similar to other beta-lactam antibacterials, carbapenems have a neurotoxic
      potential that seems to be higher than that of the penicillins and
      cephalosporins. Seizures have been reported in several large studies of patients
      treated with imipenem/cilastatin. However, it seems clear that the main factor
      increasing the risk of neurotoxicity with imipenem/cilastatin is administration
      of excessive dosages relative to bodyweight and/or renal function. If the
      manufacturer's dosage recommendations are followed, the risk of seizures in
      patients receiving this combination is minimal. With meropenem, a newly
      registered carbapenem, the safety margin with respect to neurotoxic reactions has
      been increased compared with imipenem and meropenem can be used at higher doses
      than imipenem/cilastatin. Since the neurotoxicity of beta-lactam antibacterials
      seems to be caused by an interaction with gamma-aminobutyric acid (GABA)
      receptors, other drugs with a similar mechanism of action, such as
      fluoroquinolone antibacterials, should be used with caution when combined with
      carbapenems.

PMID- 8884161
TI  - A comparative review of the adverse effects of calcium antagonists.
AB  - A large number of drugs within the 3 currently classes of calcium antagonists are
      in common medical use for the treatment of hypertension and ischaemic heart
      disease. The reported adverse effect profile for each of these drugs varies, but
      tends to hold true to drug class and are typified by the adverse reactions
      reported for nifedipine and amlodipine (dihydropyridines), diltiazem
      (benzothiazepines) and verapamil (phenylalkylamines). Minor adverse effects such
      as flushing, headache, ankle oedema, palpitations and constipation are not
      uncommon and frequently require the cessation of treatment. Of greater concern
      affecting the wide and common first-line use of calcium antagonists is the as-yet
      unresolved issue of a reportedly greater risk of myocardial infarction and death
      following the use of short-acting nifedipine in patients with a history of
      hypertension, myocardial infarction or angina. Until this issue is fully
      resolved, it would seem prudent to limit the use of this agent in 'at-risk'
      patients and to await the results of further prospective studies before a final
      conclusion can be made.

PMID- 8884162
TI  - Adverse reactions with 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy').
AB  - 3,4-Methylenedioxymethamphetamine (MDMA; 'ecstasy') is an increasingly popular
      recreational drug in the US, Western Europe and Australia. In animals, including
      nonhuman primates, MDMA is known to damage brain serotonin (5-hydroxytryptamine;
      5-HT) neurons. It is not known whether MDMA damages serotonin neurons in the
      human brain but there is some indication that it may. Although the large majority
      of individuals who have used MDMA recreationally do not develop acute
      complications, as the popularity of MDMA has increased, so have reports of
      adverse nonpsychiatric and psychiatric consequences associated with use of the
      drug. Further, since manifestations of MDMA-induced serotonin injury might only
      become apparent with age, or under periods of stress, it is possible that some
      individuals with no apparent abnormalities might develop complications over time.

PMID- 8884165
TI  - Reduction in nitric oxide synthase activity with development of an epileptogenic
      focus induced by ferric chloride in the rat brain.
AB  - Intracortical injection of iron ion has been shown to induce recurrent seizures
      and epileptic discharges in electrocorticograms. The importance of the effects of
      NO on seizure control systems and their regulation is suggested. In this paper,
      we examined the changes in nitric oxide synthase (NOS) activity in the
      epileptogenic focus induced by intracortical injection of iron ion at 5 min, 10
      min, 1 h, 3 h and 3 days. Iron ion significantly decreased NOS activity in the
      cortex at the injection site 5 min, 3 h and 3 days after injection. These results
      suggest that the formation of an epileptic focus induced by iron ion is
      accompanied by decreased NOS activity.

PMID- 8884166
TI  - Ethosuximide specifically antagonizes the effect of pentylenetetrazol in the rat
      entorhinal cortex.
AB  - This study tested two related hypotheses. The first is that the entorhinal cortex
      has an important role in synchronization and spread of epileptiform activity into
      the dentate gyrus. The second is that ethosuximide acts by antagonizing the
      action of pentylenetetrazol (PTZ) in the entorhinal cortex. Experiments were
      carried out in urethane anesthetized rats. Recording electrodes were placed in
      the dentate gyrus and stimulating electrodes were placed in the angular bundle.
      Administration of PTZ reduced the time to onset of maximal dentate activation,
      which is a marker for synchronized reverberatory seizure activity in the
      hippocampal-parahippocampal circuits. Since PTZ facilitates the spread of
      epileptiform activity in, or through, the entorhinal cortex, these results
      support the hypothesis that the entorhinal cortex can influence the spread of
      seizure activity from the entorhinal cortex into the hippocampus. Ethosuximide
      specifically, and dose-dependently, reduced the polysynaptic response in the
      dentate gyrus that is initiated by PTZ, while having no effect on the response in
      the dentate gyrus to ipsilateral angular bundle stimulation. These results
      support the hypotheses that ethosuximide can antagonize this effect of PTZ.

PMID- 8884163
TI  - A risk-benefit assessment of drugs used in the management of obsessive-compulsive
      disorder.
AB  - Established efficacy and tolerability in large multicentre controlled studies
      have made serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SRIs) the
      mainstay of monotherapy for adult obsessive-compulsive disorder (OCD). When
      compared with the selective serotonin reuptake inhibitors (SSRIs), the tricyclic
      compound clomipramine has a higher incidence of adverse effects but is well
      tolerated by most OCD patients and may confer the best overall antiobsessional
      effects. Consideration of specific adverse effect profiles, special patient
      population characteristics, drug interactions and relative cost of the various
      agents may direct clinicians in choosing the most appropriate first-line drug.
      Alternative agents as monotherapies have been explored, but none has consistently
      proven effective to date. Investigations of SRI augmentation with serotonin
      enhancing agents have also failed to demonstrate substantial benefits for
      treatment-refractory OCD. Combination treatment with SRIs and dopamine receptor
      antagonist drugs appears to provide an improved response for the subpopulation of
      OCD patients who have comorbid 'tic-spectrum' disorders, though large-scale
      studies of the efficacy and tolerability of these regimens are not yet available.

PMID- 8884167
TI  - The serotonergic innervation of the cerebral cortex in man and its changes in
      focal cortical dysplasia.
AB  - We present the morphology and the laminar distribution of the serotonin (5
      hydroxytryptamine, 5-HT) innervation of the cerebral cortex of patients who
      underwent cortical resection for partial seizures. The limits of the resections
      were established by stereoelectroencephalography. The 5-HT innervation was mapped
      by using an antiserum anti-5-HT. Two patients had cryptogenic epilepsies and two
      others had seizures related to focal cortical dysplasia. 5-HT immunoreactive
      axons were morphologically heterogeneous and projected diffusely to the cerebral
      cortex with regional-specific densities. Two types of terminal axon were
      demonstrated. Type I had large and spherical (intensely immunoreactive)
      varicosities and was distributed sparsely with a characteristic predominance in
      the molecular layer. Type II had fine and pleiomorphic varicosities (granular or
      fusiform) and was distributed through all cortical layers. The distribution of
      the 5-HT innervation varied according to the different architectonic areas
      investigated. The granular cortical areas characterized by a highly developed
      layer IV (primary somatosensory, primary visual and prefrontal cortices) had the
      highest density of 5-HT-ir fibers distributed from layer I to layer V. The
      agranular primary motor cortex had the lowest density with fibers preferentially
      seen in layers I, IIIa and V-VI. The orbital cortex with a poorly defined layer
      IV had an intermediate density with a laminar repartition predominant in the
      supragranular layers. In patients with cryptogenic epilepsies, the brain
      epileptogenic tissue was histologically normal as well as the serotonergic
      innervation. In contrast, in patients with focal cortical dysplasia, the
      dysplastic epileptogenic tissue was characterized by a serotonergic
      hyperinnervation. In agreement with previous data in primates, we give
      morphological evidence for two morphologically distinct serotonergic subsystems
      and for regional specific densities in the human cerebral cortex. Moreover, we
      previously reported an altered pattern of the catecholaminergic innervation in
      the same dysplasia areas. All these results provide evidence that this
      development epileptogenic lesion involves several sets of neurons which may
      contribute to epileptogenic activity.

PMID- 8884168
TI  - Metabolite profiles in patients on high-dose valproate monotherapy.
AB  - To investigate the mechanism of valproate (VPA)-induced hepatotoxicity, we
      measured the serum and urine metabolites of VPA in high-dose VPA monotherapy by
      GC/MS/SIM and discussed the relationship between liver function and beta
      oxidation, omega-, (omega-1)-oxidation metabolites and 4-en-VPA. In high-dose VPA
      monotherapy, the concentrations of beta-oxidation metabolites were not increased
      except for 2-en-VPA, but the concentrations of {omega + (omega-1)}-oxidation
      metabolites and of 4-en-VPA were increased about 4-5 times compared to those of
      standard dose VPA monotherapy. Serum GOT was not significantly correlated to 4-en
      VPA and the ratio of beta-oxidation/{omega + (omega-1)} oxidation metabolites of
      VPA in serum. In high-dose VPA monotherapy, it is speculated that the beta
      oxidation of VPA in the mitochondria reached the saturation point. However,
      instead of the beta-oxidation, the {omega + (omega-1)}-oxidation in microsomes
      was increased. We could not find significant relationship between the formation
      of toxic metabolites of VPA and liver dysfunction. Our data in VPA monotherapy
      suggest that the mechanisms of VPA-induced fatal hepatotoxicity cannot be
      explained by decreased beta-oxidation, increased omega-oxidation and increased 4
      en-VPA level.

PMID- 8884169
TI  - A comparison of health-related quality of life in patients with epilepsy,
      diabetes and multiple sclerosis.
AB  - The purpose of this investigation was to compare self-reported health-related
      quality of life (HRQOL) in epilepsy compared to another neurological condition or
      a non-neurological chronic illness. Patients with epilepsy (N = 271), multiple
      sclerosis (N = 85) and diabetes (N = 555) completed a generic measure of HRQOL
      (RAND 36-Item Health Survey 1.0 (SF-36)), and the eight SF-36 scale scores were
      compared across groups, adjusting for differences in sociodemographic
      characteristics and co-morbid medical conditions. Patients with multiple
      sclerosis reported significantly worse HRQOL compared to both the epilepsy and
      diabetes groups (who did not differ from one another) on the Physical
      Functioning, Role Limitations-Physical, Energy, and Social Function scales.
      Patients with epilepsy and multiple sclerosis did not differ from one another but
      reported significantly lower HRQOL scores than the diabetes group on the
      Emotional Well-Being and Role Limitations-Emotional scales. However, the epilepsy
      group reported better health perceptions compared to the diabetes and multiple
      sclerosis patients. Generic measures of HRQOL appear useful in identifying some
      effects of neurological disease, but disease-targeted supplements may be required
      to more clearly identify the impact of epilepsy on quality of life.

PMID- 8884170
TI  - Acute psychological disorders in patients with epilepsy: a nation-wide study.
AB  - Acute psychological disorders (APDs) are more common in epilepsy than in the
      general population, with estimates varying from 2 to 16% depending on the
      population of patients sampled. APD has traditionally been classified by seizure
      activity (ictal), the early post-ictal period (post-ictal) and unrelated to
      seizure activity (inter-ictal). APD may also occur as a consequence of the use of
      antiepileptic drugs (AEDs). An ongoing prospective active surveillance system was
      utilised which surveys all neurologists and associated specialists in the United
      Kingdom run by the British Neurological Surveillance Unit (BNSU). Incident cases
      were ascertained, using the BNSU, for a period of 1 year and were defined as
      patients with epilepsy who developed an acute psychological disorder, whatever
      the cause, such as a psychosis or depression. Sixty-four cases were ascertained.
      The ages were between 17 and 69 (mean 36); there were 38 males and 26 females.
      The majority of patients had location-related epilepsy (52, 81%), either
      cryptogenic (29, 45%) or secondary to a symptomatic lesion (23, 36%), of which
      the most common were mesial temporal sclerosis (6, 9%) and trauma (4, 6%). Thirty
      one (48%) patients were considered to have APD due to ictal or post-ictal
      activity. Thirty-three (52%) were inter-ictal. Carbamazepine was the most common
      AED prescribed (42, 66%), and of the new AEDs lamotrigine was prescribed in 17
      patients (27%) and vigabatrin in 16 (25%). The APD in 19 (30%) patients was
      reported by the referring physician as being secondary to an AED. In 12 patients
      this was attributed to vigabatrin. However, the relative frequency of APD due to
      AEDs, or to the different new AEDs, could not accurately be calculated as this
      was not a true incidence study. In the 19 drug-related APD patients, there was no
      change in seizure frequency in 8 (42%) and in 7 (37%) the seizure frequency had
      decreased (in 3 (16%), ceasing altogether prior to the APD). In 4 of the 19
      patients (21%) the seizure frequency increased. The overall outcome was good with
      17/19 (89%) of the AED attributed cases resolving.

PMID- 8884171
TI  - Monoamines and their metabolites in cerebrospinal fluid and temporal cortex of
      epileptic patients.
AB  - The involvement of monoamines in the initiation or maintenance of epileptic
      phenomena has been extensively studied in cerebral tissues and in cerebrospinal
      fluid. The present work was undertaken to study monoamines and their metabolites
      in human spiking and non-spiking temporal cortex excised from patients with
      complex partial seizures unresponsive to available anticonvulsants. The same
      substances were also analyzed by HPLC-ED in cerebrospinal fluid obtained 24 h
      before the surgical procedure and compared with those from patients with chronic
      headache and normal neurological evaluation. The results show increased 5-HT, 5
      HIAA and HVA levels in spiking compared with non-spiking cortex. Cerebrospinal
      fluid levels of 5-HIAA and HVA are concomitantly increased in epileptic compared
      with headache patients.

PMID- 8884164
TI  - Drug-induced disorders of glucose metabolism. Mechanisms and management.
AB  - Glucose homeostasis is maintained by a balance between the release and action of
      insulin, and the counterregulatory responses mediated principally by glucagon,
      catecholamines, growth hormone and cortisol. Hence, the effects of a drug on
      glucose metabolism may be mediated by any of these agents singly or in
      combination. Host factors, such as inherent glucoregulatory mechanisms,
      concurrent diseases, organ function and concomitant medications also increase the
      risk of drug-induced disturbances of glucose homeostasis in susceptible
      individuals. By far the most important agents causing hypoglycaemia are insulin
      and the sulphonylureas. Alcohol (ethanol), over-zealous glycaemic control,
      hypoglycaemic unawareness, detective counterregulation especially in insulin
      dependent diabetes mellitus (IDDM), and renal and liver impairment are all
      important predisposing factors. Although antihyperglycaemic agents such as
      metformin and alpha-glucosidase inhibitors do not cause hypoglycaemia alone, they
      may enhance the hypoglycaemic effects of potent hypoglycaemic agents such as
      insulin and sulphonylureas. On the other hand, the potential hypoglycaemic
      effects of ACE inhibitors, alpha-blockers, lipid-lowering agents and recombinant
      human insulin-like growth factor demonstrated in experimental settings, are of
      potential therapeutic interest. Iatrogenic hypoglycaemia and intensive insulin
      treatment are associated with hypoglycaemic unawareness which may be obviated by
      meticulous avoidance of hypoglycaemia. Effective patient education remains an
      important preventive measure. Oral glucose is used to treat mild hypoglycaemic
      episodes while more severe episodes are treated by intravenous glucose or
      glucagon. Nasal glucagon and theophylline are other experimental measures to
      improve recovery from hypoglycaemia. In refractory hypoglycaemia due to
      hyperinsulinaemia such as during sulphonylurea overdosage or quinine treatment,
      the long-acting somatostatin, octreotide, may suppress insulin release and
      restore euglycaemia. Diuretics, beta-blockers, sympathomimetics, corticosteroids
      and sex hormones are commonly prescribed drugs which may have adverse effects on
      carbohydrate metabolism especially in patients with diabetes mellitus or those
      who are at risk of developing glucose intolerance. Pentamidine was frequently
      associated with dysglycaemia due to its pancreatic beta-cell cytotoxic effects
      but is now used less often to treat Pneumocystis carinii pneumonia in
      immunosuppressed patients. Despite the large number of anecdotal reports of drug
      induced disturbances of glucose metabolism, many of the so-called adverse drug
      reactions were either idiosyncratic or coincidental. Nevertheless, they emphasise
      the complex nature of glucose homeostasis and its potential interactions with
      drugs, host factors and disease states. An understanding of these relationships
      may allow more critical interpretation of these clinical observations, better
      prediction of drug induced adverse effects on carbohydrate metabolism and the
      implementation of more rational therapy. Hence, the hypoglycaemic effects of a
      drug may be turned to a therapeutic advantage in patients with glucose
      intolerance. Similarly, the hyperglycaemic effect of a drug may help to treat
      refractory hypoglycaemia.

PMID- 8884172
TI  - Lack of linkage between idiopathic generalized epilepsies and the gene encoding
      the neural cell adhesion molecule.
AB  - Hereditary factors play a major role in the etiology of idiopathic generalized
      epilepsies (IGEs). The frequent neuropathological occurrence of microdysgeneses
      in the brain of IGE patients implies that genes regulating neural migration and
      cell adhesion might be involved in epileptogenesis of age-related generalized
      seizures. Our present linkage study tested the hypothesis that DNA sequence
      variants associated with the gene encoding the neural cell adhesion molecule
      (NCAM) confer genetic susceptibility to IGE traits in 57 families ascertained
      through patients with either juvenile myoclonic epilepsy, juvenile or childhood
      absence epilepsy. Our consistently negative results provide evidence against a
      common major effect of NCAM gene variants to the expression of IGEs with age
      related onset from childhood to adolescence.

PMID- 8884173
TI  - Patterns of desmocollin synthesis in human epithelia: immunolocalization of
      desmocollins 1 and 3 in special epithelia and in cultured cells.
AB  - Murine monoclonal antibodies (mAbs) which specifically react, in immunoblot and
      immunolocalization experiments, with the human desmosomal cadherins, desmocollins
      Dsc1 (mAb Dsc1-U100) and Dsc3 (mAb Dsc3-U114), have allowed to study
      systematically the synthesis of these proteins in tissues and cultured cells.
      Application of these mAbs in immunofluorescence microscopy on human skin has
      shown the presence of Dsc1 in the suprabasal layers of interfollicular epidermis
      and a specific cell layer of the hair follicle root sheath, whereas Dsc3 has been
      identified in all living epidermal layers as well as in glandular ducts and in
      basal matrix cells and the outer root sheath of hair follicles. Dsc3, but not
      Dsc1, it also present in desmosomes of the basal as well as suprabasal cell
      layers of other stratified epithelia such as vagina, tongue and esophagus as well
      as in cells of the basal layer of bladder urothelium and the complex epithelium
      of trachea. All the diverse one-layered ("simple") epithelia examined were as
      negative for both, Dsc1 and Dsc3, as were the non-epithelial desmosomes of the
      intercalated disks of the myocardium. A special situation has been discovered in
      the thymus. Here the usually single-layered cells of the thymic reticular
      epithelium are connected by Dsc3-possessing desmosomes, as they also contain
      typical (type I) hemidesmosomes, whereas Dsc1 is only detected in the "Hassall
      bodies", spheroidal formations of densely packed reticulum-derived cells which
      also produce cytokeratins 1 and 10, indicative of suprabasal epidermal
      differentiation. In cell cultures most, probably all, desmosomes of diverse cell
      lines derived from stratified squamous epithelia or squamous cell carcinomas,
      including primary keratinocytes, HaCaT keratinocytes and A-431 carcinoma cells,
      contain Dsc3. By contrast, Dsc1 has only been detected in local piles of
      keratinocytes that appear to be in the process of suprabasal differentiation. The
      antibodies have also allowed to demonstrate that desmosomes of cell lines can
      contain more than one desmocollin isoform. The observations made by
      immunofluorescence microscopy are compared with results obtained by in situ
      hybridization of mRNAs, and the potential value of these mAbs in histology and
      pathology is discussed.

PMID- 8884174
TI  - An antibody against a glycosylated integral membrane protein of the Xenopus
      laevis nuclear pore complex: a tool for the study of pore complex membranes.
AB  - We have recently described a monoclonal antibody (X222) which localizes at pore
      complexes in Xenopus oocytes and immunoblots a protein under nonreducing
      conditions with an apparent molecular mass of 215 kDa (Cordes, Gajewski, Stumpp,
      Krohne, Differentiation 58, 307-312, (1995)). Under reducing conditions, this
      antigen decreased from the previously reported 215 kDa to 200 kDa. Since this
      protein binds to the lectin concanavalin A (Con A), we now refer to it as gp200.
      In addition to Con A binding, Xenopus gp200 has several other features in common
      with the mammalian pore membrane protein gp210. On nuclear envelopes extracted
      with Triton X-100, gp200 was localized on the lateral walls of pores, a subdomain
      covered in native nuclear envelopes by the lipid bilayer. In mitotic extracts of
      Xenopus eggs gp200 was exclusively recovered in the membrane fraction. Treatment
      of oocyte membranes with urea and proteases indicated that gp200 is an integral
      membrane protein with the bulk of its mass located within the membrane lumen. In
      Xenopus oocyte nuclei gp200 is the major Con A binding protein. The new
      monoclonal antibody X222 has allowed us to characterize the first integral
      membrane protein, gp200, of the Xenopus pore complex.

PMID- 8884175
TI  - Conserved binding recognition elements of sperm chromatin, sperm lipophilic
      structures and nuclear envelope precursor vesicles.
AB  - Detergent-resistant, lipophilic structures (LSs) at the apex and base of the
      conical sea urchin sperm nucleus are targets for cytoplasmic membrane vesicle
      (MV) binding and fuse with these vesicles to form a nuclear envelope in vitro. We
      report similar LSs associated with trout, frog and mammalian (mouse and bovine)
      sperm nuclei. The LSs are located at the implantation fossae of all species
      examined, as well as in the ventral hook region of mouse sperm nuclei. LSs can be
      removed from, and reconstituted back to, their original sites on nuclei. LS
      removal prevents MV binding, and reconstitution restores MV binding and GTP
      induced fusion activities. Binding of LSs to chromatin or to MVs is mediated, at
      least in part, by proteins on each structure. Inter-specific LS-chromatin
      reconstitutions using sea urchin, fish, frog, and mammalian LSs indicate that
      site-specific binding is not dependent on species. All LSs also bind to MVs of
      sea urchin or bovine origin, but sea urchin MVs will only fuse with sea urchin
      LSs, and mammalian MVs only with mammalian LSs. These results demonstrate the
      conservation between echinoderms, fish, amphibians, and mammals of recognition
      elements for LS-chromatin and LS-MV binding. The mechanism for fusion of LSs with
      cytoplasmic MVs, however, is apparently not conserved, and close apposition of
      MVs on the chromatin surface mediated by LSs is not sufficient to permit MV-MV
      fusion in the presence of GTP.

PMID- 8884176
TI  - Distribution of ribosomal genes in nucleoli of herpes simplex virus type 1
      infected cells.
AB  - Herpes simplex virus type 1 (HSV-1) infection of HeLa cells induces profound
      changes in the structure of the nucleoli. They become markedly elongated, and
      their fibrillar centers become greatly diminished in number, but larger than in
      non-infected HeLa cells, and only partially surrounded by the dense fibrillar
      component. The effect of prolonged HSV-1 infection on the distribution of the
      rRNA genes was studied by means of postembedding electron microscope in situ
      hybridization using a biotinylated ribosomal DNA (rDNA) probe, which spans about
      half of the rRNA gene, and subsequent immunogold labeling of the resulting
      hybrids. Gold particles accumulated over two structures: a large solitary, finely
      fibrillar, moderately electron opaque area which was detectable only in a few
      sections of nucleoli and corresponded to the virus-modified fibrillar center, and
      over limited areas of the nucleolus-associated chromatin. In non-infected HeLa
      cells, foci of clustered rRNA genes were observed in the more frequently detected
      fibrillar centers and in association with condensed chromatin. It would be
      expected that foci of extended rDNA molecules might contain active or potentially
      active genes, whereas foci of highly compacted rDNA molecules might contain
      inactive genes. The ribosomal RNA molecules which were detected with the same
      probe over the dense fibrillar component and the granular component of the
      nucleoli of both infected and non-infected cells were not found within the rDNA
      containing foci. The data strongly suggest that the changes in the size and
      number of fibrillar centers induced by the intranuclear development of HSV-1
      might be directly linked to the well-known decrease of the nucleolar activity.

PMID- 8884177
TI  - EGF-receptor RNA metabolism in the nucleus of A431 cells.
AB  - Epidermal growth factor (EGF) receptor RNA has been shown to be localized around
      nucleoli in the nucleus of A431 cells (Sibon et al., Histochemistry 101, 223-232
      (1994)). Here we have studied the functional implication of this localization.
      Inhibition of transcription by alpha-amanitin did not influence the localization
      and amount of EGF-receptor RNA around the nucleolus, indicating that these RNAs
      represent mainly completed transcripts. Localization of the EGF-receptor genes in
      A431 cells by in situ hybridization revealed that the majority of the receptor
      gene clusters are located at the periphery of the nucleus. Next to this virtually
      all cells studied contain at least one gene cluster in the vicinity of the
      nucleolus. From these data, it is tempting to suggest that EGF-receptor gene
      transcription occurs around the nucleolus. In order to obtain information on the
      site of EGF-receptor RNA splicing, the localization of exon and intron sequences
      of the EGF-receptor transcripts was studied using a new electron microscopical
      approach. These labeling studies revealed that both intron and exon sequences
      were present at the same site around the nucleolus. In addition, exon sequences
      were also located, around nucleolus separate from intron sequences. All together,
      these studies suggest that transcription and splicing of the EGF-receptor
      transcript occurs at the same defined site around the nucleolus in A431 cells.

PMID- 8884178
TI  - Modification of the cytoplasmic domain affects the subcellular localization of
      Golgi glycosyl-transferases.
AB  - Our goal was to engineer a Golgi glycosyltransferase epitope-tagged on its
      cytoplasmically exposed, short, N-terminal domain that gave normal subcellular
      localization. Partial replacement of the cytoplasmic tail of human alpha-2,6
      sialyltransferase (SialylT) with the negatively charged myc or FLAG epitope
      resulted in almost complete mislocalization of the chimera expressed in Vero
      cells. A granular cytoplasmic staining pattern was seen by immunofluorescence.
      Spacing the negatively charged residues progressively outward from the negative N
      terminus resulted in increasingly more normal localization of myc or FLAG-tagged
      protein to a juxtanuclear Golgi-like distribution. Substitution of a neutrally
      charged VSV-G sequence for these tags resulted in normal localization of the
      chimera to the juxtanuclear Golgi region. Insertion of the myc epitope within the
      N-terminal domain of the short form of bovine beta-1,4-galactosyltransferase
      (GalT) gave a chimeric protein that mislocalized in BHK cells. No signal was
      detected with a monoclonal anti-epitope antibody indicating that the myc epitope
      was masked. Placement of myc or FLAG epitopes at the NH2-terminus of human N
      acetylglucosaminyltransferase I (GlcNAc-T) resulted in chimeric proteins that in
      Vero cells displayed little Golgi localization. We conclude that positioning of
      negative charge, in particular, close to the membrane, typically produces a
      failure of type II Golgi glycosyltransferases to exit the ER/CGN, presumably due
      to quality control mechanisms. These proteins may be successfully epitope-tagged
      on their N-terminal domain either using a neutral or positively charged sequence
      or spacing any negatively charged sequence out from the membrane.

PMID- 8884179
TI  - Brefeldin A inhibits the constitutive-like secretion of a sulfated protein in
      pancreatic acinar cells.
AB  - Sulfation is a common posttranslational modification of secretory proteins and
      serves as a valuable marker of constitutive and regulated secretory pathways. We
      investigated the cellular localization and the secretory behavior of sulfated
      macromolecules in the mouse pancreatic acinar cell. The major sulfated proteins
      of the cell were present in isolated zymogen granules, as determined by metabolic
      labeling with [35S]sulfate and subcellular fractionation. The sulfated proteins
      fell into three groups: gp300 is not secreted and is a component of the zymogen
      granule membrane; pancreatic lipase (56 kDa) and a 40 kDa protein are soluble and
      exhibit regulated secretion kinetics; and p82 is initially granule membrane
      associated, but is released from the cell with constitutive-like kinetics as a 75
      kDa protein (p75). Secretion of p75 could be stimulated for up to 4 h after pulse
      labeling, presumably from immature secretory granules, but not after 6 h of
      chase. Treatment of cells with brefeldin A (BFA) at the start of the [35S]sulfate
      pulse resulted in almost total inhibition of sulfation. Addition of BFA during
      the chase (0-2 h) allowed normal basal and stimulated secretion of regulated
      secretory proteins, but reversibly inhibited the constitutive-like secretion of
      p75. In this case, the behavior of p75 was maintained as that of a regulated
      secretory protein for up to 6 h of chase. In untreated cells, immunofluorescence
      of p82/p75 was along the acinar lumen, and in small punctate structures in the
      apical cytoplasm. In BFA-treated cells, immunolabeling of p82/p75 was lost from
      the acinar lumen, and cytoplasmic labeling was finer and appeared to be
      associated with the secretory granule membranes. These data suggest a role for
      brefeldin A-sensitive coat formation in maturation of secretory granules after
      they bud from the TGN.

PMID- 8884180
TI  - Preferential release of newly synthesized, exportable neuropeptides by insect
      neuroendocrine cells and the effect of ageing of secretory granules.
AB  - The release of newly synthesized neuropeptides was studied in an in vitro system
      using the adipokinetic hormone (AKH)-producing cells of an insect (Locusta
      migratoria) as a model system. Tritiated phenylalanine incorporated into three
      hormonal neuropeptides, AKH I, II and III, was used to distinguish newly
      synthesized hormones from older, preexisting ones. After pulse-chase labeling
      experiments of varying duration, the secretion of AKHs by the AKH cells was
      stimulated. Both hormones released into the incubation medium after stimulation
      and non-released hormones extracted from the tissue were separated by reversed
      phase high performance liquid chromatography. Their radioactivity was measured by
      scintillation counting of the column eluate. The ratio between the specific
      radioactivities of the released and the non-released neuropeptides was always
      greater than 1.0, which indicates that the newly synthesized peptides are
      preferentially released. The percentages of newly synthesized (radioactive) AKHs
      which are released, increased until 8 1/4 h and decreased thereafter. The results
      indicate that after the packaging of the prohormones into secretory granules and
      their processing to bioactive AKHs, some further maturation of the secretory
      granules is required before they can release their content. After an 8 1/4 h
      incubation, secretory granules with radioactive AHKs enter a non-releasable pool
      consisting of older secretory granules.

PMID- 8884181
TI  - Gangliosides GM1, GM2 and GM3 inhibit the platelet-derived growth factor-induced
      signalling transduction pathway in vascular smooth muscle cells by different
      mechanisms.
AB  - Gangliosides appear to regulate proliferation of different cell types. In the
      present study, we investigated the effects of gangliosides GM1, GM2 and GM3 on
      platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell (VSMC)
      growth. In addition, we examined the effects of gangliosides on the PDGF-BB
      dependent signalling transduction pathway in rat aortic VSMC. GM2 and GM1 inhibit
      the PDGF-BB-dependent receptor tyrosine autophosphorylation, stimulation of the
      PLC-gamma 1, increase of inositol-1,4,5-trisphosphate (InsP3), elevation in
      cytosolic free Ca2+ ([Ca2+]i), expression of the immediate early growth response
      gene c-fos and cell proliferation with the following rank order of potency GM2 >
      GM1. Although GM3 did not influence the PDGF-BB-dependent receptor
      autophosphorylation and PLC-gamma 1 activation, it effectively inhibited the PDGF
      BB-dependent InsP3 formation, [Ca2+]i and cell growth. Binding studies with 125I
      PDGF-BB on VSMC in the presence and absence of 10 to 50 microM of each
      ganglioside revealed that GM1 and GM2 effectively inhibited the specific binding
      of PDGF-BB with an IC50 value of 20 microM for GM2 and 30 microM for GM1. GM3 had
      no significant effect on the specific 125I-PDGF-BB binding. These observations
      suggest that GM1 and GM2 may interact with PDGF-BB or its receptor resulting in a
      prevention of its binding. GM3 was able to suppress the PDGF-BB-dependent
      increase of InsP3 and [Ca2+]i downstream of the PDGF-BB-dependent receptor
      autophosphorylation and PLC-gamma 1 activity.

PMID- 8884182
TI  - Liarozole potentiates the all-trans-retinoic acid-induced structural remodelling
      in human breast carcinoma MCF-7 cells in vitro.
AB  - Liarozole inhibits cytochrome P-450-dependent enzymes that play a key role in all
      trans-retinoic acid (ATRA) catabolism. In MCF-7 cells, liarozole potentiates the
      antiproliferative effects of ATRA. The present study demonstrates this
      synergistic effect on cell differentiation of MCF-7 cell cultures as measured by
      immunocytochemistry for cytokeratins 8, 18, and 19, actin, E-cadherin, desmoglein
      and desmoplakins I & II. ATRA concentration-dependently (10(-8) M-10(-6) M)
      induced changes in actin stress fibers and cytokeratin intermediate filaments.
      These changes were accompanied by a more obvious interaction of these filaments
      with junctional complexes. Surface area and volume of the MCF-7 cells increased
      markedly after ATRA exposure, with extensive filopodia formation. Liarozole (10(
      6) M) alone had no effect on cell morphology, cytokeratin or actin organization,
      or on cellular junctions. In combination with ATRA (10(-9) M and 10(-8) M),
      liarozole potentiated the ATRA-induced effects. The MCF-7 cell cultures used
      showed morphological heterogeneity, consisting of at least two cellular
      subpopulations. This was reflected in the staining for E-cadherin, desmoglein and
      desmoplakins I & II. ATRA increased E-cadherin staining at cell-cell contact
      sites, but had no influence on the staining patterns of desmoglein and
      desmoplakins I & II. Similar to what has been observed for the cytoskeletal
      differentiation parameters, liarozole alone had no influence on E-cadherin,
      desmoglein or desmoplakins I & II expression, but in combination with ATRA again
      intensified the effects on E-cadherin distribution. These effects on MCF-7 cells
      agree with previously obtained observations concerning the inhibition of ATRA
      catabolism by liarozole. Furthermore, our data support the hypothesis that the
      antiproliferative properties of the drug are accompanied by induction of
      differentiation.

PMID- 8884183
TI  - Response of germfree rat colonic mucous cells to peroral endotoxin application.
AB  - During microbial colonization, mucin-releasing goblet cells of germ-free (GF)
      rats proliferate and upregulate their mucin synthesis, thus improving the
      intestinal mucus barrier. The present study determined the significance of
      bacterial membrane constituents for this development. A single dose of
      lipopolysaccharide (LPS) (35 micrograms/100 g body weight) and lipid A (3.5
      micrograms/100 g body weight, respectively), was perorally administered to GF
      AS/Ztm rats. One, 3 and 5 days later, sections of the proximal and distal colon
      served for characterization of mucin-secreting goblet cells, released mucins were
      isolated in parallel. Maximal goblet cell diameters were evidenced at day 3. LPS
      generated a maximal goblet cell hyperplasia one day after challenge, lipid A
      stimulated the goblet cell proliferation continuously up to day 5. Three days
      after challenge with one of the stimuli, either, intracellular mucins had shifted
      significantly to neutral constituents. In addition, mucins, adherent to the colon
      mucosa and submerged to the luminal content, respectively, then were augmented.
      At day 5, adherent mucins were similar to the controls, while luminal, soluble
      constituents had further increased. Histometrical and biochemical methods
      evidenced a transient, inflammatory response of mucin-secreting cells, followed
      by an upregulated release of immature mucins.

PMID- 8884184
TI  - Internucleosomal DNA fragmentation in cultured cells under conditions reported to
      induce apoptosis may be caused by mycoplasma endonucleases.
AB  - DNA fragmentation is a common biochemical hallmark of apoptosis. It is catalyzed
      by endogenous Ca2+, Mg(2+)-dependent endonuclease(s). Although the exact identity
      of the apoptotic endonuclease is still a matter of debate, a number of candidate
      nucleases have been proposed like NUC18, DNase II and DNase I. Relatively large
      amounts of nucleases are also expressed by mycoplasmas, cell wall-less bacteria
      of the class Mollicutes, which are found as contaminants in up to 45% of the
      continuous cell lines in current use. In order to clarify the effect of these
      pathogens on the investigation of apoptosis in cell culture systems, we looked
      for biochemical markers (DNA fragmentation, nuclease expression) and
      morphological changes characteristic of apoptosis (cell shrinkage, chromatin
      condensation, apoptotic bodies) in Mycoplasma hyorhinis-free and -infected
      cultures of the human pancreatic adenocarcinoma cell line PaTu 8902 and of mouse
      NIH 3T3 fibroblasts. For that purpose we employed cells cultured under standard
      conditions and cells exposed to the protein synthesis inhibitor cycloheximide,
      which is known to induce apoptosis in various cell systems. After exposure to
      cycloheximide only the mycoplasma-positive cells exhibited internucleosomal DNA
      degradation. In contrast, nuclease activities in the molecular range of 47 to 54
      kDa were detected in cell homogenates and culture supernatants of infected
      cultures of both control and cycloheximide-treated cells, whereas mycoplasma-free
      cultures were nuclease-negative. The expression of the nucleases and the
      cycloheximide-induced DNA fragmentation were suppressed by the prokaryote
      specific protein synthesis inhibitor chloramphenicol. Moreover, partially
      purified nucleases from supernatants of infected cells were able to cleave the
      DNA of isolated substrate nuclei at internucleosomal sites. These data indicate
      that DNA ladder formation in cell culture systems can also be caused by
      mycoplasmal nucleases which apparently penetrate the host cells after
      cycloheximide treatment or more generally after cellular stress. Therefore,
      internucleosomal DNA fragmentation in established cell lines has to be regarded
      with care, unless mycoplasmal infection can be excluded, or the existence of
      endogenous endonucleases can be proven. The presence of endonucleolytic
      activities of about 47 to 54 kDa molecular mass has now to be regarded as highly
      indicative of contaminations with M. hyorhinis. In contrast, the expression of an
      apoptotic morphology was not restricted to infected cells; in both mycoplasma
      free and -contaminated cultures, cells with condensed chromatin were observed
      after staining with the DNA binding dye Hoechst 33342. Electron microscopic
      studies revealed that most of the cells containing compacted DNA were
      phagocytosed by unaffected fellow cells. Presumably because of the relatively
      long exposure (72 h) to cycloheximide we also observed secondary necrosis as
      indicated by the parallel occurrence of morphological characteristics of
      apoptosis (chromatin condensation) and necrosis (loss of membrane integrity and
      organelle swelling).

PMID- 8884185
TI  - Multiple fluorescence and reflectance simultaneous detection by confocal
      microscopy of HaeIII digested DNA sequences.
AB  - Human metaphase chromosomes were isolated and digested in situ with HaeIII
      restriction enzyme to detect cytosine and guanine-rich sequences (CpG islands),
      which are known to be associated with most of the mammalian genes. Digested DNA
      was reconstructed by in situ nick translation employing digoxigenin-labeled
      nucleotides. The DNA sequences were revealed by antibodies conjugated either with
      fluorescein isothiocyanate or 1-nm colloidal gold. DNA was counterstained with
      propidium iodide. A sensitive, high resolution method for visualizing three
      signals, simultaneously excited by a single argon laser line of 488 nm has been
      developed. The green fluorescence of fluorescein isothiocyanate was detected in
      combination with the red fluorescence of propidium iodide, and the third signal
      was imaged by employing the reflectance mode of the confocal microscope after
      silver enhancement of the gold beads. The high reflectance intensity, the
      accurate localization and the non-fading properties of colloidal gold made the
      reaction a valuable tool for the detection of antigens and, as a consequence, of
      specific DNA sequences in chromosome preparations. Overlaying of three signals
      allowed the simultaneous observation of distinct structures: total DNA, as well
      as fluorescein- and gold-labeled sequences after in situ nick translation, or
      total DNA and centromeric sequences of two different chromosome pairs (17 and X)
      after in situ hybridization. The use of HaeIII restriction enzyme that cut CpG
      islands combined with in situ nick translation identified the chromosome sites
      where active, inactive or housekeeping genes can be located. In chromosomes, the
      fluorescent reaction pattern showed large areas of labeling, while a more defined
      staining, often organized in spot pairs that resembled an R-like banding, was
      detected when the reflected mode was used. These results are confirmed by the
      observation that R-like bands actually are multiple symmetrical spots localized
      on sister chromatids. In addition, some chromosomes, and in particular 1 and 9,
      displayed a C-negative banding due to the negativity of the centromeric areas.
      Reflectance confocal scanning microscopy and in situ nick translation represent a
      powerful tool to study the in situ genome organization.

PMID- 8884186
TI  - An international investigation of an outbreak of Legionnaires disease among UK
      and French tourists.
AB  - Five cases of legionnaires disease and one death were associated with four
      members of a tour group from the United Kingdom (UK) and one French tourist who
      all visited Spain in the spring of 1993. The UK group stayed at four hotels, one
      of which was also used by the French tourist. Phenotypic and genotypic comparison
      of isolates of Legionella pneumophila obtained from one of the UK cases and the
      French patient demonstrated that they were indistinguishable from each other and
      from environmental isolates obtained from the water supply of the hotel at which
      all five cases had stayed. A cohort study of the UK tour group was carried out to
      determine the extent of the outbreak and showed that three further members of the
      group had respiratory illness but were serologically negative to legionella
      infection. International participation in this investigation has highlighted the
      value of a European surveillance scheme and the benefit of microbiological
      collaboration between legionella reference laboratories in Europe.

PMID- 8884187
TI  - Quality of life assessment and HIV infection: a review.
AB  - In the last few years, survival of patients infected with human immunodeficiency
      virus (HIV) has been improved because of a decreased incidence of some
      opportunistic complications attributable to prophylactic treatments and
      antiretroviral drugs. The impact of these agents should also be reflected in the
      quality of life (QoL) of patients. We have reviewed this topic with an emphasis
      on different types of measurements such as Q-TWIST, MOS and the Spitzer score
      which seem to be most appropriate for this patient population. We do not think
      that a special type of assessment should be designed for HIV-infected persons. It
      would be less time-consuming to improve already existing validated scores
      focusing on HIV infection. QoL in intravenous drug users with HIV should be
      evaluated more often.

PMID- 8884188
TI  - A meta-analysis of estimates of the AIDS incubation distribution.
AB  - Information from 12 studies is combined to estimate the AIDS incubation
      distribution with greater precision than is possible from a single study. The
      analysis uses a hierarchy of parametric models based on a four-parameter
      generalized F distribution. This general model contains four standard two
      parameter distributions as special cases. The cases are the Weibull, gamma, log
      logistic, lognormal distributions. These four special cases subsume three
      distinct asymptotic hazard behaviors. As time increases beyond the median of
      approximately 10 years, the hazard can increase to infinity (Weibull), can
      plateau at some constant level (gamma), or can decrease to zero (log-logistic and
      lognormal). The Weibull, gamma and 'log-logistic distributions' which represent
      the three distinct asymptotic hazard behaviors, all fit the data as well as the
      generalized F distribution at the 25 percent significance level. Hence, we
      conclude that incubation data is still too limited to ascertain the specific
      hazard assumption that should be utilized in studies of the AIDS epidemic.
      Accordingly, efforts to model the AIDS epidemic (e.g., back-calculation
      approaches) should allow the incubation distribution to take several forms to
      adequately represent HIV estimation uncertainty. It is recommended that, at a
      minimum, the specific Weibull, gamma and log-logistic distributions estimated in
      this meta-analysis should all be used in modeling the AIDS epidemic, to reflect
      this uncertainty.

PMID- 8884189
TI  - Seroprevalence of hepatitis A virus infection among sewage workers in the
      Parisian area, France.
AB  - Sewers are an ideal environment to be occupationally exposed to viral hepatitis A
      (HAV) infection, because of high frequency and ability of the virus to remain
      viable for prolonged periods in sewage. However, data on the occupational risk of
      HAV infection among sewage workers is not well documented. In a cross sectional
      study comparing sewage workers (n = 155) to those not occupationally exposed to
      it (n = 70), we found a non significant increase in HAV seropositivity among
      sewage workers of 12.9% (p = 0.07). The prevalence of HAV antibody was
      significantly associated with duration of occupational exposure to sewage (p <
      0.015), stay in HAV endemic areas (p < 0.03), age (p < 0.001), and number of
      siblings (p < 0.03). A stepwise logistic regression analysis gave an adjusted
      odds ratio for HAV seropositivity 2.15 fold greater in sewage workers compared to
      those not occupationally exposed to it. So, although there was no significant
      difference in the prevalence of HAV antibody between sewage workers and others,
      exposure to sewage was an independent risk factor for HAV seropositivity, and
      this raises the question of whether it is necessary to vaccinate sewage workers
      against viral hepatitis A.

PMID- 8884190
TI  - Sexual transmission of hepatitis C virus infection.
AB  - The role of sexual transmission in the diffusion of HCV infection, was studied
      through the seroprevalence of anti-HCV antibodies in the heterosexual habitual
      partners of 83 anti-HCV positive subjects. The index cases were represented by 10
      dialysed subjects, 31 patients with chronic liver disease and 42 healthy
      carriers. Seroprevalence of anti-HCV positivity reported in partners was 8.43%,
      with a higher rate in cohabitants of patients with chronic liver disease (16.12%
      vs 4.76% of carriers); no case was found among partners of dialysed subjects
      Laboratory and ultrasonograph signs of chronic hepatitis were reported in 3 cases
      (3.61%). Control on 70% of the cohabitants' relatives, was negative for HCV
      infections. These data suggest a possible sexual transmission of HCV infection,
      even if its prevalence resulted modest, undoubtedly lower than in other disease
      sexually transmitted.

PMID- 8884191
TI  - Seroepidemiological survey of Q fever in Leon province, Spain.
AB  - A seroepidemiological survey, using an indirect immunofluorescence test against
      Coxiella burnetii (antigenic phase II), was carried out in Leon province, north
      western Spain. A total of 406 serum samples was collected from people (from 15 to
      more than 65 years old) living in a rural environment during the winter and
      spring of 1994. The overall prevalence was 40.6%, titres ranged from 1:80 to
      1:640, and a titre of 1:80 was encountered among 60.6% of positive samples. A
      significant higher prevalence was observed among males globally, as well as among
      those aged 15-44 and 45-64 years old; however, no difference was encountered
      among males and females older than 64 years. In the same way, a significant
      higher Q fever prevalence was observed among individuals having occupations
      related to agriculture and among those having close relationship with animals.

PMID- 8884192
TI  - Low prevalence of diphtheria immunity in the population of Florence, Italy.
AB  - A seroepidemiological study was conducted in 1994 on a representative sample of
      the population of Florence in order to verify the immunity coverage against
      diphtheria. Subjects were divided according to sex and age class. Sera from each
      selected class were at least 1.5/1000 of the residing population. Diphtheria
      antitoxin was titrated using a quantitative ELISA test. The results show an
      overall adjusted prevalence of diphtheria immunity (> or = 0.01 IU/ml) equal to
      63.7%. Subjects of younger age classes have good protection levels (85.5% immune
      under 30 years), while only half individuals aged > or = 50 years have antibody
      titres > or = 0.01 IU/ml. Full protection (antibody titre > or = 0.1 IU/ml) was
      detected only in a very small proportion of those aged > or = 40 years. Our data
      show (1) how a recrudescence of diphtheria could theoretically take place in
      older subjects living in Italy, and (2) stress the importance of periodical re
      vaccination of adults.

PMID- 8884193
TI  - Prospective serological study of leptospirosis in southern Spain.
AB  - This article reports data concerning a serosurvey carried out in Southern Spain
      to assess the current epidemiological status of a population exposed to risk of
      leptospirosis. Microagglutination and IgM-EIA tests were carried out on sera from
      a sample of workers in agriculture-related occupations, exposed to marsh waters.
      A cohort of 197 workers were followed for a year in an active surveillance
      program to evaluate seroconversion (laboratory confirmed leptospirosis). The
      results have shown for the cohort a density of incidence: 6.4 x 100 persons per
      year, and for the reference population an accumulated incidence of 41.25/100,000.
      Prevalence rates (P) were 21.3 x 100 and 144 x 10(5) for the cohort and
      population respectively. Rates were higher in cray-fishers (P: 62.7%), rice
      workers, and butchers. This is the first report identifying cray-fishers as a
      high risk group for leptospirosis, and the reporting of human contamination by
      Australis serogroup in Spain.

PMID- 8884194
TI  - Spirometric prediction equations for male Italians 7-18 years of age.
AB  - The purpose of this study was to develop spirometric predictive equations (SPE)
      for forced vital capacity (FVC), forced expiratory volume in one second (FEV1)
      and maximum midexpiratory flow (MMF25-75) derived from a large sample of healthy
      italian boys and male adolescents. We used the univariate and multiple linear
      regression models and considered as independent variables age and the following
      anthropometric measurements: height, weight, chest circumference. The predictive
      power of multivariate models was slightly higher than that of the univariate
      model using height as independent variable for FVC, FEV1 and MMF25-75.

PMID- 8884195
TI  - Frequency of radiographic procedures in an urban 62-year-old population in
      relation to general health, body build, bone mineral content, locomotor
      discomfort, occupational work load and socio-economic factors.
AB  - For 830 62-year-old residents of the city of Malmo records of radiographic
      examinations made over a period of 40 years at the Radiological Department of
      Malmo General Hospital and/or over 20-30 years at two private radiological
      departments in the city were reviewed. Radiographic examination had been
      undertaken in 92% of the residents, with on an average 16 examinations per
      resident. The most common examinations were of the chest in 63% of the residents
      followed by lower limb (58%) and spine (52%) examinations. In men the total
      number of radiographic examinations were negatively correlated to income,
      intelligence test results and social network and job satisfaction. Men with
      monotonous work and a more restricted latitude for decision-making at work, as
      well as men who were smokers had also had significantly more radiographic
      examinations. Single civil status and occupational work load had in men a
      positive correlation with the total number of radiographic examinations, as well
      as with serum levels of glutamyltransferase and uric acid levels. In women there
      was a negative correlation between radiographic examinations and teachers' rating
      of intelligence in childhood and bone mineral content, whereas job satisfaction,
      life success and triceps skinfold index (= subcutaneous fat tissue thickness) had
      a positive correlation with the total number of radiographic examinations. Women
      who took regular exercise (every week) had had significantly fewer radiographic
      examinations. Men and women with locomotor discomfort had a significantly higher
      consumption of not only musculoskeletal radiographic examinations but also other
      radiographic examinations.

PMID- 8884196
TI  - Snoring and atherosclerotic manifestations in a 70-year-old population.
AB  - A number of studies have demonstrated an association between habitual snoring and
      ischemic heart disease like angina pectoris, myocardial infarction and ischemic
      changes on the electrocardiography (ECG). Control for the influence of potential
      confounders has been inadequate. To further elucidate the issue we examined the
      association between self-assessed snoring and the relation to atherosclerotic
      manifestations. 804 70-year-old males and females were classified according to
      snoring habits. Alcohol and tobacco consumption, blood pressure, body mass index,
      social group, plasma lipids (triglycerides, cholesterol, high density
      lipoprotein), fasting blood glucose, glucose tolerance test, plasma epinephrine
      and norepinephrine were determined. Presence of angina pectoris, claudication
      intermittens, use of nitroglycerine were questioned, a resting ECG and a distal
      arterial pressure by use of doppler technique in the lower limbs were determined.
      Distal atherosclerotic manifestations was defined as complaints of claudication
      intermittens, pulselessness in one or more foot arteries or a foot/arm systolic
      pressure ratio < 0.90. ECG changes were classified in accordance to standard
      criteria (Minnesota codes) into positive ECG signs (Q/OS waves, S-T depressions,
      T-wave inversion or flattering or left bundle branch block) and definitive
      myocardial infarction. Snoring showed a weak positive correlation to positive ECG
      signs and definitive myocardial infarction, but after adjustments for the above
      confounders, no association was found between snoring and atherosclerotic
      manifestations. We conclude that, in a 70-year-old population, self-reported
      snoring is not associated with atherosclerotic manifestations.

PMID- 8884197
TI  - Seasonal prevalences of Cryptosporidium and Giardia infections in children
      attending day care centres in Salamanca (Spain) studied for a period of 15
      months.
AB  - Five studies were carried out in children younger than 4 years old attending
      regularly day care centres in order to determine the intestinal parasitization by
      Cryptosporidium and Giardia. The percent of children parasitized by
      Cryptosporidium was 10% (17 children out of 170 studied). Cryptosporidiosis was
      more frequent in winter than in other seasons (difference statistically
      significant). Giardia intestinalis, which was the most frequent parasite, was
      identified in 25.3% (43 children out of 170 studied). Giardiasis was more
      frequent in autumn and in the low SEL (difference statistically significant in
      both cases). The frequency of giardiasis increased from 8% in children studied
      during 1-2 seasons, to 34% in children studied for 3-5 seasons (difference
      statistically significant), whereas the frequency of cryptosporidiosis did not
      show variation with increased number of specimens studied per child. The 35% of
      children parasitized by Cryptosporidium sp. showed gastrointestinal symptoms but
      only 14% of children with Giardia intestinalis.

PMID- 8884198
TI  - Prevalence study of different hepatitis markers among pregnant Albanian refugees
      in Greece.
AB  - Aim of the study was to record the prevalence of the various types of viral
      hepatitis, especially hepatitis B, in pregnant Albanian refugees in Greece. The
      study comprised 500 pregnant refugees of mean age 25.1 +/- 4.6 years. In Albania,
      all women had lived in overcrowded houses and had been exposed to non throw-away
      needles and syringes. Various indices for all hepatitis types were determined.
      The prevalence of HBsAg was 13.4%, of anti-HBs 53%, of total anti-HBc 70.8%, of
      anti-HBc IgM 0.4%, of HBeAg 1.2%, of anti-HBe 58.6%, of anti-HAV 96.2%, of anti
      HAV IgM 1%, of anti-HDV 0.4%, of anti-HCV 0.6% and of anti-HEV 2%. HBeAg was
      found positive in 7.5% of HBsAg carriers. Prevalence of hepatitis B markers, as
      determined by HBsAg and/or anti-HBs and/or total anti-HBc was significantly
      higher in those with a history of previous hospitalization in Albania (p = 0.01)
      and those with previous history of hepatitis (p = 0.02). The high prevalence of
      hepatitis B markers in pregnant Albanian refugees proves that HBV infection is
      highly endemic in Albania and the possibility of perinatal transmission to the
      offsprings urges for HBV vaccination programmes. On the other hand improvements
      in the socioeconomic conditions and the sanitation system in Albania is
      anticipated to reduce the incidence of HAV and HBV infections.

PMID- 8884199
TI  - Rubella infection during pregnancy in the 1985-86 epidemic: follow-up after seven
      years.
AB  - The study covered 310 pregnant women from southern Poland who were exposed to
      rubella during the 1985-86 epidemic, none of whom had been vaccinated against
      rubella. Rubella specific antibodies were detected by hemagglutination-inhibition
      (HI) tests, and IgM antibodies by enzyme immunoassay (ELISA) (Organon Teknika).
      Clinical symptoms according to anamnesis were recorded. The consequences of
      serologically confirmed maternal rubella on the course of pregnancy and on fetal
      outcome were evaluated. IgM antibodies could be examined in only 10 newborns at
      delivery or in the first days of life. After seven years, follow-up studies of
      children born to infected mothers were done. The mental development of 14 of
      these children was evaluated with Terman-Merrill test. Among 310 women examined
      during pregnancy, rubella infection was confirmed serologically in 46 cases
      (14.8%). All but 3 of those had clinical symptoms. The course of pregnancy was
      observed in 36 of the infected mothers. Only 5 women (22.7%) who had the
      infection in the first trimester of pregnancy delivered a healthy child. The rate
      of complications in pregnancy among women infected in the second trimester was
      lower, and 8 (66.7%) bore healthy children. All the children born to mothers
      infected in the third trimester were healthy. Eight of the 10 newborns examined
      at delivery were IgM positive. Of 29 children congenital rubella syndrome (CRS)
      was confirmed in 5 cases, CRS compatible or CRS possible in 7 and 3 had
      congenital infection only confirmed serologically (IgM-positive) without defects
      or symptoms. Seventeen (58.6%) children were found healthy including the 3 who
      had congenital infection only. The mental development of 14 children at age 7 was
      assessed; 10 cases (72%) fell within rank II 130-85, and 4 (28%) were of
      borderline intelligence. The study indicates that congenital rubella is still a
      serious problem in Poland. Immunization was introduced only in 1988-89, for 13
      year-old girls. Women of child-bearing age should be screened for rubella
      antibodies and those susceptible to rubella infection should be vaccinated.

PMID- 8884200
TI  - Subtyping of Bacillus cereus by total cell protein patterns and arbitrary primer
      polymerase chain reaction.
AB  - Bacillus cereus is a ubiquitous sporeforming Gram-positive rod that is associated
      with foodborne outbreaks as well as several opportunistic infections. Inspite of
      the prevalence of B. cereus associated foodborne outbreaks, subtyping of the
      species using molecular typing assays was not attempted. In this study we have
      recovered 58 B. cereus isolates from natural and clinical sources and initially
      characterized them, along with a B. cereus strain (ATCC 14579) and B.
      thuringiensis natural isolate, by biotyping, antibiotic susceptibility testing,
      and SDS-PAGE of total cell proteins. Our data have shown the existence of 1
      biotype, 3 anti-biograms and 22 (38%) total cell protein patterns among the 58 B.
      cereus isolates. B. thuringiensis had a different protein pattern. SDS-PAGE of
      total cell proteins data denote clonal heterogeneity within B. cereus. Protein
      pattern 4 (pp4) was the most predominant with 13 isolates of B. cereus showing
      this pattern. Eight out of the 13 isolates with pp4 and one B. cereus strain
      (ATCC 14579) were further subtyped by using the arbitrary primer polymerase chain
      reaction (AP-PCR) assay. Eight (88.8%) different PCR patterns out of the 9 B.
      cereus isolates were obtained. Patterns obtained by SDS-PAGE of total cell
      proteins and AP-PCR were reproducible. These results indicate that SDS-PAGE of
      total cell proteins allows the differentiation among species within Bacillus and
      of strains within B. cereus. The typability of the method was 100% and the
      simpson's discrimination index of diversity was 98%. The utility of SDS-PAGE of
      total cell proteins in a pilot epidemiologic study was assessed and results
      obtained demonstrate its typing potential. AP-PCR allows further subtyping of the
      species. Both methods if used in conjunction may be useful for further clinical
      and epidemiologic studies of the spectrum of diseases caused by B. cereus.

PMID- 8884201
TI  - Determinants of current HIV risk behaviour among injecting drug users in Warsaw,
      Poland.
AB  - Of the injecting drug users (IDUs), 24% had borrowed, and 37% had passed on
      syringes in the previous 6 months. In logistic regression analysis, current
      borrowing of syringes was significantly associated with a shorter duration of
      injecting drug use, a higher number of drug-injecting sex partners in the
      previous 6 months, and with current lending of syringes. A majority of the IDUs
      have modified previous HIV risk behaviour but these modifications are
      insufficient and not sustained over time. Intensified AIDS prevention measures
      for IDUs in Poland are needed.

PMID- 8884203
TI  - What is wrong with the term Balkan endemic nephropathy?

PMID- 8884202
TI  - Utility of an anonymous questionnaire for the identification of a primary
      transmission route and possible secondary transmission in adults with acute
      hepatitis B virus infection.
AB  - By letting adults with acute hepatitis B virus (HBV) infection answer an
      anonymous questionnaire covering risks associated with the acquisition and
      further transmission of HBV infection, we found that a likely relevant
      transmission route could be identified in most patients. Despite being informed
      of the diagnosis, 50% of the patients exposed others via sexual contact during
      their contagious period.

PMID- 8884204
TI  - Effects of nimodipine, felodipine and amlodipine on electroconvulsive shock
      induced amnesia in the rat.
AB  - The effects of various doses (0.03, 0.1, 0.3 or 1.0 mg/kg) of the Ca2+ channel
      blockers nimodipine, felodipine and amlodipine on the learning ability of rats
      exposed to electroconvulsive shock were examined. The animals were trained in a
      passive avoidance procedure. The drugs tested were injected 30 min before the
      learning trial started. The electroconvulsive shock was given immediately after
      the learning trial response had been acquired. A passive avoidance retention test
      was performed 24 h later. It was found that electroconvulsive shock strongly
      impaired the retention of the passive avoidance response. Nimodipine, felodipine
      and amlodipine did not influence the passive avoidance behavior in the sham
      electroconvulsive shock group, but significantly improved the retention deficits
      in the animals exposed to electroconvulsive shock. These findings support the
      hypothesis that perturbations in Ca2+ homeostasis can contribute to the memory
      deficits associated with electroconvulsive shock. The antiamnestic effects of the
      substances tested make them interesting candidates for clinical trials in
      patients with cognitive impairment caused by electroconvulsive shock therapy.

PMID- 8884205
TI  - Pharmacology of ACEA-1416: a potent systemically active NMDA receptor glycine
      site antagonist.
AB  - Excitatory amino acid receptor antagonists show potential for the treatment of
      ischemic stroke and head trauma. In search of novel antagonists, a series of
      alkyl- and alkoxyl-substituted 1, 4-dihydro-2,3-quinoxalinediones were
      synthesized and assayed for inhibition of glutamate receptors. We report on the
      pharmacological characterization of one such compound, 7-chloro-6-methyl-5-nitro
      1,4-dihydro-2, 3-quinoxalinedione (ACEA-1416). Electrophysiological assays showed
      that ACEA-1416 is a potent antagonist of rat brain NMDA receptors expressed in
      Xenopus oocytes, and NMDA receptors expressed by cultured rat cortical neurons.
      Antagonism is via competitive inhibition at glycine co-agonist sites (Kb = 7.9 nM
      in oocytes, Kb = 11 nM in neurons). ACEA-1416 also antagonizes AMPA receptors,
      though potency is considerably lower (Kb = 3.5 microM in oocytes, Kb = 1.6 microM
      in neurons). Oocyte assays indicated that ACEA-1416 is weak or inactive as an
      antagonist at NMDA receptor glutamate binding sites (Kb > 5.9 microM) and
      metabotropic glutamate receptors (Kb > 57 microM). Many NMDA receptor glycine
      site antagonists show poor penetration of the blood-brain barrier. Systemic
      bioavailability of ACEA-1416 was assessed by measuring the ability of the
      compound to protect against electroshock-induced seizures in mice. Protective
      effects of ACEA-1416 had rapid onset following i.v. administration. Peak efficacy
      was at approximately 2 min and the biological half-time of protection was
      approximately 60 min. The ED50 measured at peak efficacy was approximately 1.5
      mg/kg. Our results show that ACEA-1416 is a high potency systemically active NMDA
      receptor glycine site antagonist and a moderate potency AMPA receptor antagonist.
      Separate studies indicate that ACEA-1416 is efficacious as a neuroprotectant in a
      rat model of focal cerebral ischemia. Taken together, our results suggest that
      ACEA-1416 has potential for clinical development as a neuroprotectant.

PMID- 8884206
TI  - Neuroprotective effects of 7-nitroindazole in the gerbil model of global cerebral
      ischaemia.
AB  - To evaluate the role played by nitric oxide in global cerebral ischaemia we
      examined the effects of 7-nitroindazole and a sodium salt of 7-nitroindazole
      (inhibitors of neuronal nitric oxide (NO) synthase) and NG-nitro-L-arginine
      methyl ester (a more general inhibitor of NO synthase) in the gerbil model of
      cerebral ischaemia. Four experiments were carried out. In the first experiment,
      animals were either sham-operated, subjected to 5 min bilateral carotid occlusion
      (BCAO) or administered 7-nitroindazole or NG-nitro-L-arginine methyl ester
      immediately after occlusion followed by three further doses at 3, 6 and 24 h post
      occlusion. In the second experiment, we examined the effects of a sodium salt of
      7-nitroindazole, which is more soluble than 7-nitroindazole, using the same
      protocol. In the third experiment, the effects of the sodium salt of 7
      nitroindazole administered at 10 mg/kg at 0, 3, 6, 24, 27, 30, 33, 52, 55, 72, 75
      and 78 h post-occlusion or at 0.05 mg/h for 72 h via mini-pumps were evaluated.
      In separate experiments, we examined the effects of three reference compounds
      dizocilpine (MK-801), 2, 3-dihydroxy-6-nitro-7-sulphamoyl-benz(F)-quinoxaline
      (NBQX) and eliprodil using the same model. Extensive neuronal death was observed
      in the CA1 layer of the hippocampus in 5 min bilateral carotid occluded animals 5
      days after surgery. Both 7-nitroindazole and NG-nitro-L-arginine methyl ester
      provided significant neuroprotection (P < 0.01) against this neuronal death. The
      sodium salt of 7-nitroindazole showed no protection when administered up to 12
      times post-occlusion, but did provide significant (P < 0.01) neuroprotection when
      administered via mini-pump. The neuroprotection was similar to that provided by
      MK-801 and eliprodil, but not as good as that observed with NBQX. These results
      indicate that nitric oxide plays a role in ischaemic cell death and that
      selective neuronal nitric oxide synthase inhibitors can protect against ischaemic
      brain damage.

PMID- 8884207
TI  - Possible role of nitric oxide in the antinociceptive action of intraventricular
      bradykinin in mice.
AB  - The i.c.v. administration of bradykinin (4, 8 and 16 micrograms) induced
      antinociception in mice which was resistant to naloxone; furthermore, the
      induction of tolerance to morphine by a single s.c. injection (100 mg/kg, 24 h
      before test doses of the peptide) did not affect antinociception. Since
      bradykinin is known to increase nitric oxide (NO) in peripheral tissues, we
      studied the possibility that its antinociceptive action may be related to NO
      effects in the central nervous system. Bradykinin effects were antagonized by
      previous treatment with NG-nitro-L-arginine or concomitant i.c.v. administration
      of bradykinin and methylene blue. The immediate precursor of NO, L-arginine,
      which by itself produces analgesia, also reduced bradykinin effects; moreover,
      tolerance to L-arginine significantly decreased the response to the peptide.
      These results suggest that NO is involved in antinociception induced by i.c.v.
      administration of bradykinin.

PMID- 8884208
TI  - Pharmacological characterization and autoradiographic localization of dopamine
      receptors in the rat adrenal medulla.
AB  - The pharmacological profile and the anatomical localization of dopamine D1-like
      and D2-like receptors were studied in sections of rat adrenal medulla, with
      radioligand binding and autoradiographic techniques, respectively. [3H]([R]-(+)
      chloro-2,3,4,5-tetrahydro-5-phenyl-1 H-3benzazepin-al hemimaleate) (SCH 23390)
      was used as a ligand for dopamine D1-like receptors and [3H]spiperone was used as
      a ligand for dopamine D2-like receptors. Radioligand binding and light microscope
      autoradiography did not show specific [3H]SCH 23390 binding in sections of rat
      adrenal medulla. This suggests that rat adrenal medulla does not express dopamine
      D1-like receptors. [3H]Spiperone was specifically bound to sections of rat
      adrenal medulla. The binding was time-, temperature- and concentration-dependent,
      with a dissociation constant (Kd) of 1.05 nM and a maximum density of binding
      sites (Bmax) of 100.2 +/- 3.8 fmol/mg tissue. The pharmacological profile of
      [3H]spiperone binding to rat adrenal medulla was similar to that displayed by
      neostriatum, which is known to express dopamine D2 receptors. Light microscope
      autoradiography showed the accumulation of specifically bound [3H]spiperone as
      silver grains within sections of adrenal medulla. Silver grains were found
      primarily over the cellular membrane of chromaffin cells. The above data indicate
      that chromaffin cells of the rat adrenal medulla express dopamine receptors
      belonging to the dopamine D2 receptor subtype. These receptors are probably
      involved in the modulation of catecholamine release from chromaffin cells, as
      documented by functional studies.

PMID- 8884209
TI  - NG-nitro-L-arginine methyl ester reduces necrotic but not apoptotic cell death
      induced by reversible focal ischemia in rat.
AB  - During cerebral ischemia, nitric oxide (NO) production via stimulation of NO
      synthase, is likely one of the major events leading to neuronal death. Recently,
      we have demonstrated that after reversible focal ischemia, apoptosis was
      implicated in the penumbra whereas necrosis was prominent in the ischemic core.
      We have now examined the effect of a non-specific inhibitor of NO synthase, NG
      nitro-L-arginine methyl ester (L-NAME, 3 ing kg-1 i.p., 5 min and 3 h after the
      onset of ischemia), on the progress of apoptotic and necrotic nuclei following
      transient focal cerebral ischemia, using DNA electrophoresis and terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL
      assay). Our results indicated that L-NAME prevented the loss of necrotic, but not
      apoptotic cells.

PMID- 8884210
TI  - Peripheral kappa 1-opioid receptor-mediated analgesia in mice.
AB  - When injected directly into the tail, U50,488H is a potent analgesic in the
      tailflick assay (ED50 3.1 micrograms). The analgesic activity is lost if the
      radiant heat is focused 1 cm away from the site of injection. The kappa 1-opioid
      receptor antagonist nor-binaltorphimine given systemically reverses the local
      analgesic response of U50,488H, but the antagonist is 100-fold more potent when
      injected directly into the tail. Intrathecal antisense treatment with a probe
      targeting the mRNA encoding the kappa 1-opioid receptor blocks the local
      analgesic actions of U50,488H in the tail, suggesting that U50,488H is acting on
      dorsal ganglia neurons.

PMID- 8884211
TI  - Ethanol inhibition of stress-related tachycardia involves medullary NMDA
      receptors.
AB  - In rats, neurons in the perifornical area of the hypothalamus send descending
      projections to the commissural part of the nucleus tractus solitarii as
      demonstrated by an anterograde tracer study. In urethane-anaesthetised rats,
      stimulation of neurons in the perifornical area by microinjection of bicuculline
      or 6-OH-saclofen causes tachycardia and inhibits baroreflex bradycardia. The
      effects elicited from the perifornical area are similar in magnitude to those
      elicited from the adjacent dorsomedial nucleus, also called the hypothalamic
      defense area. Microinjection into the nucleus tractus solitarii of the NMDA (N
      methyl-D-aspartate) receptor antagonist, AP-7 (2-amino-7-phosphonoheptanoic
      acid), inhibits the tachycardic response to stimulation of the perifornical area.
      Injection of ethanol intravenously or into the nucleus tractus solitarii also
      inhibits this tachycardic response, but causes no further inhibition when
      combined with AP-7. We conclude that the perifornical area is part of the
      hypothalamic defense area, and it is under strong, tonic GABAergic inhibition
      mediated by both GABAA and GABAB receptors. Furthermore, descending input from
      the perifornical area to the nucleus tractus solitarii is via an NMDA synapse,
      and ethanol inhibits stress-related tachycardia by inhibiting these NMDA
      receptors in the nucleus tractus solitarii.

PMID- 8884212
TI  - Nitrotyrosine attenuates the hemodynamic effects of adrenoceptor agonists in
      vivo: relevance to the pathophysiology of peroxynitrite.
AB  - Peroxynitrite, which attenuates catecholamine-mediated hemodynamic responses in
      vivo, nitrates free tyrosine residues to form the specific product, 3-nitro-L
      tyrosine. The chemical structure of 3-nitro-L-tyrosine is similar to that of the
      endogenous catecholamines. Therefore, 3-nitro-L-tyrosine may interfere with
      catecholamine hemodynamic function in vivo. The hemodynamic responses produced by
      norepinephrine (1-4 micrograms/kg, i.v., n = 6), epinephrine (0.5-4
      micrograms/kg, i.v., n = 7), phenylephrine (1-8 micrograms/kg, i.v., n = 5), and
      isoproterenol (100-400 ng/kg, i.v., n = 5) were attenuated, while the hemodynamic
      responses produced by arginine vasopressin (50-250 ng/kg; i.v., n = 5) were
      unaffected following the administration of 3-nitro-L-tyrosine (2.5 mumol/kg,
      i.v.) in pentobarbital-anesthetized rats. These results demonstrate substantial
      and selective attenuation of the hemodynamic effects produced by alpha- and beta
      adrenoceptor agonists, raising the possibility that 3-nitro-L-tyrosine may play a
      role in the hemodynamic dysfunction associated with inflammatory conditions in
      which the formation of peroxynitrite is favored.

PMID- 8884213
TI  - Balloon angioplasty and induction of non-endothelial nitric oxide synthase in
      rabbit carotid arteries.
AB  - The purpose of the study was to evaluate whether balloon angioplasty is
      associated with changes in nitric oxide synthase (NO synthase) activity. Normal
      rabbit carotid arteries were examined 10 min or 1, 2, 3 or 10 weeks after
      angioplasty with 2 or 2.5-mm balloons. Immunohistology was used to evaluate
      intimal thickening and endothelial cell regeneration. The NO synthase activity
      was studied functionally using isolated segments in organ chambers.
      Immunohistochemistry of the endothelial cell markers von Willebrand factor and
      platelet endothelial cell adhesion molecule-1 indicated that the regeneration of
      endothelial cells from patchy islands that remained after angioplasty was
      virtually complete within 2 weeks. However, the endothelium-dependent relaxations
      elicited by acetylcholine remained impaired up to 10 weeks after dilation.
      Contractions elicited by 5-hydroxytryptamine (5-HT) were attenuated, but were
      significantly augmented by the NO synthase blocker, nitro-L-arginine.
      Furthermore, in contrast to normal arteries, the balloon-treated arteries
      developed marked contractions in response to nitro-L-arginine methyl ester (L
      NAME), contractions which could be reversed by L-arginine. The latter
      contractions and relaxations were not influenced by endothelial removal. These
      results suggest that although the endothelium quickly regenerates after severe
      balloon injury, the endothelium-dependent release of nitric oxide remains
      disturbed. However, the functional data also suggest that angioplasty led to a
      significant induction of NO synthase in 'non-endothelial' cells of the artery.

PMID- 8884214
TI  - Study of in vivo and in vitro resting vasodilator nitric oxide tone in
      normotensive and genetically hypertensive rats.
AB  - The effects of NG-nitro-L-arginine (L-NNA) on mean arterial pressure and the
      effects of both L-NNA and methylene blue on isolated aorta tone, were studied in
      order to elucidate potential alterations in vasodilator resting nitric oxide (NO)
      tone in genetic hypertension. L-NNA produced a significantly greater increase of
      mean arterial pressure in spontaneously hypertensive rats (SHR) than in Wistar
      Kyoto (WKY) rats; in both cases, L-arginine completely inhibited the L-NNA
      hypertensive effect. Neither ganglion blockade with hexamethonium nor
      cyclooxygenase inhibition with indomethacin significantly modified the effect of
      L-NNA in both rat strains. In intact aorta rings, after submaximally contraction
      with KCI (25 mM), both L-NNA and methylene blue induced strong dose-dependent
      contractions. The maximum contractions were, however, significantly greater in
      WKY rats than in SHR. The mechanical elimination of endothelium markedly
      inhibited both L-NNA and methylene blue maximum contractions. In intact rings, L
      arginine completely inhibited the L-NNA effects in both rat strains; in rubbed
      rings, the L-arginine inhibitory effects were strong in WKY rats but not
      important and erratic in SHR. L-Arginine had no effect on the contractions
      induced only by KCI in any of the preparations. In WKY rat-rubbed rings, sodium
      nitroprusside was significantly more effective in relaxing the contractions in
      response to 25 mM KCI than the contractions in response to methylene blue. These
      results indicate that contractions induced by L-NNA and methylene blue in
      isolated aorta are principally due to the inhibition of an important endothelial
      resting vasodilator NO tone. They also show that hypertension reduces the resting
      vasodilator NO tone in isolated rat aorta, in spite of enhancing the total
      vasodilator NO tone in anaesthetized rat.

PMID- 8884215
TI  - Vascular reactivity to angiotensin II in blood-perfused kidneys of hypertensive
      diabetic rats.
AB  - The present study examined vascular reactivity to angiotensin II in blood
      perfused kidneys of diabetic normotensive Wistar-Kyoto (WKY) and diabetic
      spontaneously hypertensive rats (SHR). In addition, the effect of the angiotensin
      AT1 receptor antagonist, CV-11974 (2-ethoxy-l-[[2'-(1 H-tetrazol-5-yl)biphenyl-4
      yl]methyl]-1 H-benzimidazole-7-carboxylic acid), on angiotensin II responses was
      examined. Dose-response curves to angiotensin II (0.1-30 micrograms/kg, i.a.)
      were obtained in kidneys of control- and diabetic-WKY rats and -SHR rats, either
      in the absence or presence of CV-11974 (3 micrograms/kg, i.v.). In all four
      treatment groups, angiotensin II produced dose-dependent increases in renal
      perfusion pressure with the order or reactivity: control-SHR > control-WKY =
      diabetic-SHR > diabetic-WKY. In the presence of CV-11974 (3 micrograms/kg, i.v.),
      dose-response curves to angiotensin II were significantly inhibited in kidneys of
      control-SHR and -WKY rats. However, CV-11974 (3 micrograms/kg, i.v.) had no
      significant effect on angiotensin II responses in kidneys of diabetic-SHR or -WKY
      rats. These results suggest that diabetes in normotensive rats is associated with
      impaired renal responsiveness to angiotensin II, while hypertension augments
      renal responsiveness to angiotensin II. However, the combination of diabetes and
      hypertension has largely offset the opposite effects on angiotensin II responses
      seen separately. Importantly, the lack of effect of CV-11974 in diabetic rats,
      with or without hypertension, has been identified. While the reasons for these
      alterations have yet to be determined, they may involve changes in angiotensin II
      receptor mechanisms (e.g. density and/or affinity).

PMID- 8884216
TI  - Bosentan improves renal regional blood flow in rats with experimental congestive
      heart failure.
AB  - The effects of the mixed endothelin receptor antagonist bosentan on renal
      regional haemodynamics were investigated in rats with aorto-caval fistula, an
      experimental model of congestive heart failure. A matched group of normal rats
      served as control. Injection of bosentan (10 mg/kg i.v.) to the rats with
      decompensated congestive heart failure produced an increase in cortical (+20%)
      and medullary (+12%) blood flow, and a decrease in vascular resistance in the
      cortex (-30%) and medulla (-23%), while reducing mean arterial pressure by
      approximately 10 mm Hg. In rats with compensated congestive heart failure and in
      normal animals, infusion of bosentan did not affect blood pressure and cortical
      perfusion. These findings indicate that 1) endothelin receptor blockade produces
      beneficial effects on renal haemodynamics in rats with experimental congestive
      heart failure and 2) endothelin-1 may be involved in the pathogenesis of renal
      hypoperfusion only in decompensated congestive heart failure.

PMID- 8884217
TI  - Effect of experimental diabetes on rat prostate endothelin receptors.
AB  - We studied the properties of endothelin receptors in the prostate of 8-week
      streptozotocin-diabetic and control rats. The density of endothelin receptors, as
      determined by saturation experiments with [125I]endothelin-1, were 95.8 +/- 5.4
      and 171.3 +/- 16.7 fmol/mg of protein in control and diabetic rat prostates,
      respectively. The pharmacological profile of the endothelin receptors was similar
      in both groups and was consistent with the predominance of the endothelin ETA
      receptor subtype in the prostate. Thus, the induction of diabetes upregulates the
      expression of endothelin receptors in the rat prostate, but does not alter the
      pharmacological profile of the receptors in these tissues.

PMID- 8884218
TI  - Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide
      biosynthesis.
AB  - The effect of chronic N omega-nitro-L-arginine methyl ester (L-NAME) treatment on
      the in vivo eosinophil migration induced by bradykinin, platelet-activating
      factor (PAF), lipopolysaccharide and carrageenin has been investigated in the rat
      using the pleurisy model. The in vitro (microchemotaxis chamber) eosinophil
      migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), PAF and
      zymosan-activated serum was also evaluated in the rat. The eosinophils were
      obtained from the peritoneal cavity of male Wistar rats and isolated on a
      discontinuous metrizamide gradient. Chronic inhibition of nitric oxide
      biosynthesis was achieved by adding L-NAME to the drinking water to give an
      intake of approximately 75 mumol/rat/day for 4 weeks. Rats treated chronically
      with L-NAME developed a significant level of hypertension (163 +/- 4.8 mmHg; P <
      0.01) compared with animals which received either the same dose of the inactive
      enantiomer D-NAME (124 +/- 3.2 mmHg) or tap water alone (119 +/- 1.6 mmHg). The
      intrapleural injection of bradykinin (50 micrograms), PAF (1 microgram),
      lipopolysaccharide (0.25 microgram) and carrageenin (125 micrograms) into
      untreated rats in vivo induced a significant level of eosinophil migration by 24
      h post-injection. This migration was markedly reduced in L-NAME-treated rats.
      Eosinophils obtained from untreated rats showed a significant level of migration
      in vitro in response to fMLP (5 X 10(-8) M), PAF (10(-8) M) and zymosan-activated
      serum (27 microliters). In contrast, the migration induced by these chemotactic
      agents was markedly reduced in cells isolated from animals treated chronically
      with L-NAME. L-Arginine (5.5 mM), but not D-arginine (5.5 mM), restored the
      ability of eosinophils from L-NAME-treated animals to migrate in response to
      fMLP. Our results indicate that nitric oxide plays a major role in the in vivo
      and ex vivo migration of eosinophils.

PMID- 8884219
TI  - Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis
      factor-alpha.
AB  - Murine macrophage-derived tumor necrosis factor alpha (TNF-alpha) gene expression
      has been shown to be dramatically induced by bacterial lipopolysaccharide, and to
      be dependent upon nuclear factor-kappa B (NF-kappa B) binding sites in its
      promoter for the lipopolysaccharide induction. Murine J774.1 macrophage cells
      were found to predominantly express the adenosine A3 receptor RNA relative to
      adenosine A1 receptor or adenosine A2 receptor RNA. Adenosine receptor agonists,
      in a dose-dependent manner characteristic of the adenosine A3 receptor, blocked
      the endotoxin induction of the TNF-alpha gene and TNF-alpha protein expression in
      the J774.1 macrophage cell line. The adenosine A3 receptor antagonist BW-1433
      dose-dependently reversed this adenosine inhibitory effect on TNF-alpha gene
      expression. Thus, the binding of adenosine receptor agonists to the adenosine A3
      receptor interrupts the endotoxin CD14 receptor signal transduction pathway and
      blocks induction of cytokine TNF-alpha, revealing a novel cross-talk between the
      murine adenosine A3 receptor and the endotoxin CD14 receptor in J774.1
      macrophages.

PMID- 8884220
TI  - Antiproliferative and receptor binding properties of alpha- and beta-casomorphins
      in the T47D human breast cancer cell line.
AB  - In previous studies, we have shown that opioid agonists ([D-Ala2, D
      Leu5]enkephalin (DADLE), [D-Ser2, Leu5]enkephalin-Thr6 (DSLET),
      ethylketocyclazocine and etorphine) bind to opioid binding sites and decrease
      cell proliferation of human T47D breast cancer cells. Furthermore, we provided
      evidence about a cross-reaction, also in the T47D human breast cancer cell line,
      of mu-acting opioids with type-II somatostatin receptors. Since a potential
      source of opioid activity in the breast might be casomorphin peptides (produced
      by the enzymatic degradation of alpha-casein and beta-casein), we investigated
      the antiproliferative action of five different casomorphin peptides: alpha-casein
      (90-95), alpha-casein-(90-96), beta-casomorphin, beta-casomorphin-(1-5) and
      morphiceptin. We show that all five peptides decreased, in a dose-dependent
      manner, cell proliferation. The general antagonist diprenorphine produced only a
      partial reversal of their action. Furthermore, we provide evidence that all
      peptides (except for morphiceptin) bind to delta- and kappa-opioid binding sites
      of T47D cells with different selectivity. Finally, we show that these peptides
      are also partial competitors at the somatostatin receptors present in the same
      cell line.

PMID- 8884221
TI  - Diazepam-insensitive GABAA receptors in rat cerebellum and thalamus.
AB  - Three major populations of GABAA receptor binding sites are present in cerebellar
      membranes: diazepam-sensitive [3H]Ro15-4513 binding sites, diazepam-insensitive
      [3H]Ro15-4513 binding sites and high-affinity [3H]muscimol binding sites. All
      three populations contain a beta subunit as shown by immunoprecipitation with
      antibodies that recognize all beta subunits. The beta 3 subtype of beta subunit
      is contained in all three populations, but only a similar low fraction (< 20%) in
      each. Thus, the majority contain beta subunits other than beta 3 (beta 2 and beta
      1) and beta 3 subunits are not selectively associated with nor lacking in any of
      the three binding populations. Antibodies to the gamma 2 subunit precipitated
      similar fractions of [3H]Ro15-4513, [3H]flunitrazepam and [3H]muscimol binding
      sites, showing that gamma 2 subunits are present in high-affinity muscimol
      binding isoforms, as well as a significant fraction of the diazepam-insensitive
      [3H]Ro15-4513 binding sites. Under conditions that identify the 56 kDa alpha 6
      subunit on SDS-PAGE as the diazepam insensitive site of [3H]Ro15-4513 binding in
      cerebellum, no polypeptide showing diazepam-insensitive binding of [3H]Ro15-4513
      could be photoaffinity-labeled in rat thalamus. These results suggest that alpha
      4 subunits in the thalamus participate primarily in subunit combinations which
      bind muscimol but not any benzodiazepine site ligands.

PMID- 8884222
TI  - Cyclic AMP levels in ventricular myocytes from noradrenaline-treated guinea-pigs.
AB  - Chronic activation of the sympathetic nervous system in human heart failure is
      believed to cause cardiac beta-adrenoceptor desensitisation. We have investigated
      the relationship between beta-adrenoceptor desensitisation and cyclic AMP levels
      in cardiac myocytes isolated from the ventricle of guinea-pigs chronically
      infused with noradrenaline hydrochloride for 7 days. Functional beta-adrenoceptor
      desensitisation was confirmed by a significant decrease in the maximum
      isoprenaline-stimulated contraction amplitude and an increased EC50 for
      isoprenaline. In the absence of beta-adrenoceptor stimulation, basal cyclic AMP
      levels were significantly depressed in populations of myocytes from noradrenaline
      treated animals compared to sham-operated controls, and this was not accounted
      for by myocyte hypertrophy or necrosis. Similarly, there was a significant
      decrease in cyclic AMP levels at maximally inotropic isoprenaline concentrations.
      Threshold and maximum inotropic concentrations of the phosphodiesterase
      inhibitor, 3-isobutyl-l-methylxanthine (IBMX), restored isoprenaline-stimulated
      cyclic AMP levels in noradrenaline-treated guinea-pig cardiac myocytes, although
      we have previously reported no increase in maximum inotropic effect of
      isoprenaline with these compounds.

PMID- 8884223
TI  - Autoradiographic study on the pharmacological characteristics of [3H]3-OH-PCP
      binding sites in rat brain.
AB  - The pharmacological characteristics and the regional distribution of [3H]3-OH-PCP
      (1-[1(3-hydroxyphenyl)-cyclohexyl]piperidine) binding were investigated in rat
      brain by quantitative autoradiography. Kinetic analysis of [3H]3-OH-PCP binding
      revealed fast and slow components, in the association and dissociation studies.
      The regional distribution of binding closely corresponded to those of binding
      sites labeled by [3H]N-[l-(2-thienyl)-cyclohexyl]3,4-piperidine (TCP) and [3H](+)
      5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate (MK 801).
      High densities of [3H]3-OH-PCP binding sites were found in the stratum radiatum
      and orients of field CA1 in the hippocampus and in the outer layers of cerebral
      cortices. In contrast, low levels of binding were seen in the brain stem and the
      granular cell layer of the cerebellum. [3H]3-OH-PCP binding was strongly
      inhibited by MK 801 and 3-OH-PCP, while the potency of (+)-SKF 10047 in
      inhibiting [3H]3-OH-PCP binding was less in the cerebral cortex and hippocampus.
      The antagonists for the glutamate, glycine and polyamine recognition sites at the
      NMDA/PCP receptor complex displaced [3H]3-OH-PCP binding sites with a potency
      similar to that of [3H]MK 801. These findings suggest that the [3H]3-OH-PCP
      binding site is similar or identical to the PCP binding site labeled by [3H]TCP
      and [3H]MK 801.

PMID- 8884224
TI  - Adenosine A2 receptor activation facilitates 45Ca2+ uptake by rat brain
      synaptosomes.
AB  - Adenosine has been shown to increase the release of neurotransmitters by
      stimulation of adenosine A2 receptors. This effect probably depends on Ca2+ entry
      into presynaptic nerve terminals. In the present work the ability of the mixed
      adenosine A1/A2 agonist, 2-chloroadenosine, to stimulate Ca2+ uptake into rat
      brain synaptosomes was investigated. 45Ca2+ uptake was induced by 20 microM
      veratridine. In the absence of other drugs, 2-chloroadenosine (1 microM)
      decreased 45Ca2+ uptake into synaptosomes. Blocking the adenosine A1 receptor
      with 100 nM of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), 2-chloroadenosine (1
      microM) increased rather than decreased the uptake of 45Ca2+ into synaptosomes.
      The excitatory effect of 2-chloroadenosine observed in the presence of DPCPX was
      reversed by 200 nM of omega-agatoxin-IVA, a specific P-type Ca2+ channel
      antagonist, but not by L-type (nifedipine, 100 nM to 1 microM; methoxyverapamil 1
      10 microM) or N-type (omega-conotoxin GVIA, 500 nM) Ca2+ channel antagonists. The
      adenosine A2A selective agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethyl
      carboxamido-adenosi ne (CGS 21680), did not significantly modify Ca2+ uptake
      induced by veratridine. In contrast, the selective adenosine A2 receptor agonist,
      N6-(2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)-adenosine (DPMA), in
      concentrations ranging from 10 nM to 1 microM increased Ca2+ uptake induced by
      veratridine. The selective adenosine A2 receptor antagonist 3,7-dimethyl-1
      propargylxanthine (DMPX) at a concentration of 10 microM antagonized the
      stimulatory effect of DPMA (0.1 microM) on 45Ca2+ uptake. In conclusion,
      activation of adenosine A2 receptors increases Ca2+ uptake by synaptosomes
      depolarized by veratridine, which could explain the increase of neurotransmitter
      release observed when A2 receptors are activated.

PMID- 8884225
TI  - Binding of [3H](+)-BW373U86 to delta-opioid receptors in rat brain membranes.
AB  - A tritiated form of the non-peptide delta-opioid receptor agonist (+)-BW373U86
      ((+)-4-((alpha-R)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-l-piperazinyl)-3
      hydroxybenzyl)-N,N-diethylbenzamide) was synthesized and its binding
      characteristics studied. [3H](+)-BW373U86 bound with subnanomolar affinity to rat
      brain membranes and was displaced most effectively by ligands selective for delta
      opioid receptors. Naltrindole, naltriben, and 7-benzylidenenaltrexone exhibited
      apparent inhibition constants of 0.06, 1.54, and 4.49 nM, respectively, while mu-
      or kappa-selective ligands showed little affinity for this site. [3H](+)-BW373U86
      binding was sensitive to the presence of guanine nucleotides; GDP caused a 3-fold
      decrease and 5'-guanylyl-imidodiphosphate (Gpp[NH]p) caused a 25% increase in
      binding affinity.

PMID- 8884226
TI  - Site-directed mutagenesis of the human adenosine A2A receptor. Critical
      involvement of Glu13 in agonist recognition.
AB  - A glutamic acid residue in the first transmembrane domain of the human adenosine
      A2A receptor was mutated to glutamine. Radioligand binding studies on COS-7 cell
      membranes expressing either the wild-type or the mutant receptor revealed that
      the affinity of the prototypic agonist CGS21680 (2-[4-[(2
      carboxyethyl)phenyl]ethylamino]-5'-N-ethylcarboxamidoadenosine ) for the mutant
      receptor was 15-fold lower than for the wild-type receptor. This was confirmed in
      functional studies with intact cells. The EC50 values of CGS21680 for the
      stimulation of cAMP production differed in a similar way. Antagonists of various
      chemical structure were equally effective on both mutant and wild-type receptors,
      thus the mutation selectively diminishes agonist affinity. We propose an indirect
      perturbation of the binding site, perhaps through a proton transfer mechanism as
      suggested by molecular modelling.

PMID- 8884227
TI  - Imidazoli(di)ne compounds interact with the phencyclidine site of NMDA receptors
      in the rat brain.
AB  - The effects of several imidazoli(di)ne compounds on the binding of the non
      competitive NMDA receptor antagonist [3H](+)-MK-801 (dizocilpine) to rat brain
      membranes were studied. These compounds fully inhibit radioligand binding with
      potencies in the micromolar range. The obtained profile of drug affinity
      correlated well with the potency of the same compounds promoting insulin release
      by blocking ATP-sensitive K+ channels in the rat insulinoma cell line RIN-5AH. It
      is suggested that imidazoli(di)ne compounds interact with cation channels sharing
      a common phencyclidine binding site (e.g. NMDA receptors, K+ channels and
      nicotinic acetylcholine receptors) and that this could be the basis of some
      biological effects of imidazoli(di)nes.

PMID- 8884228
TI  - Phorbol ester blocks the increase of a high affinity GTPase activity induced by
      delta 2-opioid receptor agonist in the mouse spinal cord.
AB  - The high affinity GTPase activity in the mouse spinal cord was increased in a
      concentration-dependent manner by a selective delta 2-opioid receptor agonist, [D
      Ala2]deltorphin II (0.1-1 microM). This increase of GTPase activity induced by [D
      Ala2]deltorphin II was completely blocked by co-incubation with a selective delta
      2-opioid receptor antagonist, naltriben (0.1 microM). A protein kinase C
      activator, phorbol 12,13-dibutyrate (PDB; 0.1-10 microM), which given alone had
      no effect on basal GTPase activity, blocked dose-dependently the increase of
      GTPase activity induced by [D-Ala2]deltorphin II (1 microM). Our results indicate
      the possibility that activation of protein kinase C by phorbol ester uncouples
      the delta 2-opioid receptor from G-proteins in the spinal cord.

PMID- 8884229
TI  - Effect of citalopram, a selective serotonin reuptake inhibitor, on the
      acquisition of conditioned freezing.
AB  - The present study examined the effects of the selective serotonin (5
      hydroxytryptamine, 5-HT) reuptake inhibitor citalopram on the acquisition of
      conditioned freezing, an index of anxiety. Acute treatment with citalopram (1-10
      mg/kg) dose dependently prevented the acquisition of conditioned freezing, while
      acute treatment with noradrenaline or dopamine reuptake inhibitors failed. The
      acute effect of citalopram was not antagonized by the 5-HT1A receptor antagonist
      NAN190, 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl]piperazine or the 5
      HT2A/2C receptor antagonist ICI169,369, 2-(2-dimethylaminoethylthio)-3
      phenylquinoline hydrochloride. These results indicate that selective 5-HT
      reuptake inhibitors reduce not only the expression of conditioned freezing as
      reported previously, but also the acquisition of conditioned freezing. Both these
      effects of selective 5-HT reuptake inhibitors may be related to their clinical
      efficacy in the treatment of anxiety disorders.

PMID- 8884230
TI  - Effects of central administration of tachykinin receptor agonists and antagonists
      on plus-maze behavior in mice.
AB  - This study assessed the effects of intracerebroventricular administration of
      selective agonists and antagonists for tachykinin NK1 and NK2 receptors on
      performance of mice in the elevated plus-maze, an ethological model of anxiety.
      Mice were treated with either vehicle (5 microliters) or 1, 10, 100 or 500 pmol
      of substance P, neurokinin A, the selective NK1 receptor agonist substance P
      methyl ester, or the selective NK2 receptor agonist, [beta-Ala8]neurokinin A-(4
      10). Other mice received similar doses of FK 888, i.e., N2-[(4R)-4-hydroxy-1-(1
      methyl-1 H-indol-3-y)carbonyl-L-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-L-
      alaninamide, or SR 48968, i.e., (S)-N-methyl-(N-[4-acetylamine-4
      phenylpiperidine)-2-(3, 4-dichlorophenyl)buthyl]benzamide, selective antagonists
      of tachykinin NK1 and NK2 receptors, respectively. Injections of substance P,
      neurokinin A, substance P methyl ester or [beta-Ala8]neurokinin A-(4-10)
      significantly reduced the frequency of open arm entries, and [beta
      Ala8]neurokinin A-(4-10) also enhanced the percentage of entries into enclosed
      arms. Conversely, the NK1 antagonist FK 888 and the NK2 antagonist SR 48968 each
      increased the time spent in the open arms, and SR 48968 also increased the
      frequency of entries into the open arms. None of the tachykinin receptor agonists
      or antagonists modified motor performance and coordination on the rotarod
      apparatus or ambulation in an activity cage. Together, these results suggest that
      centrally administered NK1 and NK2 receptor agonists and antagonists can modulate
      anxiety, as evaluated in the elevated plus-maze test in mice. Stimulation of
      either tachykinin NK1 or NK2 receptors induces anxiogenic-like responses, whereas
      the reverse occurs following their blockade. The anxiolytic-like profiles of
      action of both tachykinin NK1 and NK2 receptor antagonists suggest that central
      tachykinin mechanisms are tonically involved in the modulation of anxiety.

PMID- 8884231
TI  - Inhibition of feeding by a nitric oxide synthase inhibitor: effects of aging.
AB  - Nitric oxide has been demonstrated to play a role in the modulation of food
      intake. With advancing age, there is a physiological decrease in food intake. The
      effect of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl
      ester (L-NAME) on food intake in C57BL/6Nnia mice aged 3, 12 and 24 months was
      studied. L-NAME was more effective at decreasing food intake in 12- and 24-month
      old mice than in the 3-month-old mice. NO synthase levels in the hypothalamus
      were increased in 16- and 25-month-old mice compared to 6-month-old mice (P <
      0.01). NO synthase mRNA increased in 16- compared to 6-month-old mice, but
      decreased in 25-month-old mice. Overall, these studies may suggest that nitric
      oxide may play an increasingly important role in the feeding drive with advancing
      age.

PMID- 8884232
TI  - Alterations of protein mono-ADP-ribosylation and diabetic neuropathy: a novel
      pharmacological approach.
AB  - This study monitored the extranuclear endogenous mono ADP-ribosylation of
      proteins. At least 10 proteins were ADP-ribosylated in a crude extract from
      control superior cervical ganglia, and 7 were labeled in control dorsal root
      ganglia; whereas in the diabetic rat the extent of labeling was reduced. These
      data suggest that proteins of peripheral ganglia are excessively ADP-ribosylated
      in vivo. Treatment of diabetic animals with silybin, a flavonoid with ADP
      ribosyltransferase inhibitory activity, did not affect hyperglycemia, but
      prevented the alterations in the extent of mono-ADP-ribosylation of proteins.
      This effect was associated with the prevention of substance P-like
      immunoreactivity loss in the sciatic nerve. In the membrane fraction of sciatic
      nerve Schwann cells, at least 9 proteins were ADP-ribosylated, in diabetic rats
      the extent of labeling was increased. A comparable increase involving the same
      proteins was triggered by chronic nerve injury and by corticosteroid treatment.
      Silybin treatment of diabetic rats prevented such an increase. We propose that
      the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented
      the onset of diabetic neuropathy, while the silybin effect on mono-ADP
      ribosylation of Schwann cells is likely indirect and secondary to the improvement
      of diabetic axonopathy.

PMID- 8884233
TI  - Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending
      serotonergic systems.
AB  - The centrally acting muscle relaxant cyclobenzaprine was thought to be an alpha 2
      adrenoceptor agonist that reduced muscle tone by decreasing the activity of
      descending noradrenergic neurons. In the present study, we examined the effects
      of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in
      rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently
      and this effect was not inhibited by the alpha 2-adrenoceptor antagonists
      idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression
      was not attenuated by noradrenergic neuronal lesions produced by 6
      hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex
      facilitation induced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5
      HT2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by DL-p
      chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the
      monosynaptic reflex. These results suggest that cyclobenzaprine is a 5-HT2
      receptor antagonist and that its muscle relaxant effect is due to inhibition of
      serotonergic, not noradrenergic, descending systems in the spinal cord.

PMID- 8884235
TI  - Genotypic differences in mesolimbic enkephalin gene expression in DBA/2J and
      C57BL/6J inbred mice.
AB  - The DBA/2J and C57BL/6J (herein referred to as DBA and C57) inbred mouse strains
      exhibit low and high predispositions for voluntary ethanol consumption,
      respectively, but the neurobiological basis underlying this differential drug
      vulnerability remains poorly understood. Comparison of endogenous brain
      proenkephalin gene expression showed the C57 mouse, compared to the DBA mouse,
      had lower preproenkephalin mRNA abundance, proenkephalin concentration and
      processed [Met5]enkephalin-immunoreactive peptide levels in the mid brain. No
      strain differences in enkephalin gene expression was observed in the striatum,
      hypothalamus, or medulla pons. Neurochemical analysis of C57 mice, following high
      voluntary ethanol consumption (approximately 17 g/kg/day), revealed markedly
      higher enkephalin gene expression in the striatum and mid brain compared to
      ethanol-naive animals. These findings suggested that mesolimbic enkephalin is
      augmented following ethanol consumption, and that endogenous low enkephalin
      biosynthesis may be associated with an increased vulnerability for ethanol abuse.
      However, the neurobiological basis of this behaviour may not be quite this
      simple. C57 mice pretreated with the dopamine receptor agonist, bromocriptine,
      had reduced striatum and mid brain preproenkephalin mRNA levels, and showed a 41%
      lower voluntary ethanol consumption compared to controls. We conclude that
      functional connectivity exists between enkephalin and dopamine systems, and
      although low mesolimbic enkephalin may predispose to high ethanol preference,
      dopamine is a more important determinant than enkephalin in the hierarchy of
      neurotransmitter pathways that mediate the increased vulnerability for ethanol
      consumption in the C57 mouse.

PMID- 8884234
TI  - Anti- and proconvulsive actions of levcromakalim, an opener of ATP-sensitive K+
      channel, in the model of hippocampus-generating partial seizures in rats.
AB  - We assessed the effect of an opener of ATP-sensitive K+ channel, levcromakalim
      (BRL 38227, (-)6-cyano-3,4-dihydro-2, 2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H
      1-benzopyran-3-ol) on seizure threshold and severity of the hippocampus
      generating partial seizures in rats. For comparison, an ATP-sensitive K+ channel
      blocker, glibenclamide; K+ channel blocker, tetraethylammonium; Ca2+ channel
      antagonist, nimodipine and Ca2+ channel agonist, (+/-)-BAY K 8644 (1,4-dihydro-2,
      6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridinecarboxyli c acid
      methyl ester) were also examined. Seizure threshold was determined using pulse
      number threshold and seizure severity was ascertained using afterdischarge
      duration. Levcromakalim decreased afterdischarge duration at 10 nmol i.c.v. and
      decreased pulse number threshold at 100 nmol i.c.v. Tetraethylammonium at 10 nmol
      i.c.v. increased afterdischarge duration selectively and at 100 nmol i.c.v.
      induced spontaneous seizures. Glibenclamide (1-100 nmol i.c.v.) failed to change
      pulse number threshold and afterdischarge duration. Nimodipine (40 mg/kg i.p.)
      decreased afterdischarge duration and pulse number threshold. BAY K 8644 (1 mg/kg
      i.p.) decreased pulse number threshold and increased afterdischarge duration. In
      addition, voltage-clamp recording from neuroblastoma x glioma hybrid cells
      indicates that levcromakalim inhibited the fast component of Ca(2+)-dependent K+
      currents, in addition to the inhibition of T- and L-types of voltage-dependent
      Ca2+ currents reported (Ito et al., FEBS Lett. 262, 313, 1990). These results
      suggest that levcromakalim shows anti- and proconvulsive actions in the
      hippocampus-generating partial seizures in rats and these effects might be, at
      least partly, caused by inhibiting Ca2+ channel and Ca(2+)-dependent K+ channel,
      respectively.

PMID- 8884236
TI  - Possible mechanism of the potent vasoconstrictor responses to ryanodine in dog
      cerebral arteries.
AB  - Isolated cerebral (basilar, posterior communicating and middle cerebral) arteries
      exist in a partially contracted state. To determine the Ca(2+)-buffering function
      of sarcoplasmic reticulum in the resting state of cerebral arteries, the effects
      of ryanodine that eliminates the function of sarcoplasmic reticulum, on tension
      and cellular Ca2+ level were compared in endothelium-denuded strips of the
      cerebral, coronary and mesenteric arteries of the dog. The addition of ryanodine
      to strips with basal tone caused a concentration-dependent contraction, which was
      significantly greater in the cerebral arteries than in the mesenteric or coronary
      artery. In the presence of 10(-5) M ryanodine, the caffeine (20 mM)-induced
      contraction was greatly attenuated in these arteries. After washout, the basal
      tone was greatly elevated in the cerebral arteries. The elevated tone was
      abolished by 10(-7) M nifedipine. The ryanodine-induced contractions were also
      abolished by 10(-7) M nifedipine. Nifedipine itself caused a relaxation from the
      basal tone in the cerebral arteries, suggesting the maintenance of myogenic tone.
      The basal Ca2+ influx in arteries measured after a 5-min incubation with 45Ca was
      significantly higher in the basilar artery than in the mesenteric artery. The
      basal Ca2+ influx was not increased by 10(-5) M ryanodine in either artery. The
      basal Ca2+ influx was decreased by 10(-7) M nifedipine in the basilar artery, but
      was unchanged in the mesenteric artery. These results suggest that: (1) the basal
      Ca2+ influx via L-type voltage-dependent Ca2+ channels was higher in the resting
      state of the cerebral arteries; (2) the greater part of the higher Ca2+ influx
      was buffered by Ca2+ uptake into the sarcoplasmic reticulum; and (3) therefore
      the functional elimination of sarcoplasmic reticulum by ryanodine caused a potent
      contraction in these arteries. Furthermore, the maintenance of myogenic tone in
      the cerebral arteries suggests that more Ca2+ enters the smooth muscle cell than
      the buffering ability of sarcoplasmic reticulum can handle.

PMID- 8884237
TI  - Actions of Daiichi DQ-2511 on electrical and synaptic behavior of enteric neurons
      in the guinea-pig small intestine.
AB  - Intracellular recording of electrical and synaptic behavior of neurons in the
      enteric nervous system of guinea-pig small intestine was used to evaluate actions
      of DQ-2511 (3-[[[2-(3, 4-dimethoxyphenyl)ethyl]carbamoyl]methyl]amino-N
      methylbenzamide). DQ-2511 is a new drug with gastrointestinal prokinetic action.
      DQ-2511 was most effective in the nanomolar range. The drug depolarized some of
      the neurons and this was accompanied by increased input resistance and augmented
      excitability. DQ-2511 in nanomolar concentrations increased the amplitude of fast
      excitatory postsynaptic potentials at nicotinic synapses. Slow inhibitory
      postsynaptic potentials, produced by release of norepinephrine from sympathetic
      postganglionic fibers, were suppressed by DQ-2511. This appeared to reflect
      presynaptic suppression of release of norepinephrine because postsynaptic
      responses to exogenously applied norepinephrine were unaffected. The results
      suggest that the prokinetic action of DQ-2511 on gastrointestinal transit might
      emerge from actions that augment excitatory synaptic transmission in the
      microcircuits of the enteric nervous system while suppressing inhibitory
      sympathetic neurotransmission.

PMID- 8884238
TI  - Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal
      propulsion in mice.
AB  - The role of 5-HT3 receptors in the control of intestinal propulsive activity was
      investigated in mice by a simple method in which the time taken for excretion of
      the head of an orally administered non-absorbable marker (whole gut transit time)
      was measured. Selective 5-HT3 receptor antagonists ramosetron (YM060) at 0.01-0.3
      mg/kg s. c. and ondansetron at 0.1-1 mg/kg s.c. dose-dependently prolonged the
      whole gut transit time. Prokinetic benzamides, such as renzapride (0.3-10 mg/kg
      s.c.), zacopride (0.01-0.3 mg/kg s.c.) and cisapride (0.1-3 mg/kg s.c.), which
      have been reported to possess 5-HT3 receptor blocking properties, also dose
      dependently prolonged it. These results indicate that activation of 5-HT3
      receptors seems to be one factor that underlies the physiological control of
      intestinal propulsive activity in mice. In contrast to their beneficial
      therapeutic effects on gastroduodenal dysmotility, prokinetic benzamides, at
      least those which have 5-HT3 receptor antagonistic activity, may be unsuitable in
      the treatment of impaired lower intestinal propulsive activity.

PMID- 8884239
TI  - The effect of NG-monomethyl-L-arginine on bladder function.
AB  - Recent studies have demonstrated the presence of nitric oxide synthase (NO
      synthase) in lower urinary tract tissues, however, its role in the detrusor is
      unclear. The current study was designed to determine if NO synthase inhibition
      alters detrusor activities, including micturition volume threshold, and
      inhibition of pelvic nerve-evoked contractions by various stimuli. In naive,
      anesthetized adult cats, inhibition of pelvic nerve-evoked bladder contractions,
      induced by hypogastric nerve stimulation or the intraarterial administration of
      NA, ATP, adenosine, beta,gamma-methylene ATP and 2-methylthio ATP, was measured
      before and after inhibition of NO synthase. The micturition volume threshold was
      also measured before and after NO synthase inhibition. L-NMMA decreased the
      micturition volume threshold by 38% (2 mg intravesical administration) or 80% (4
      mg/kg i.a.). The magnitude of the micturition contractions was modestly
      increased. These results, and information in the literature, indicate that NO may
      play a role in the collection phase of the bladder cycle and any alteration of
      nitric oxide availability could induce or allow development of various bladder
      malfunctions, such as small bladder diseases, like interstitial cystitis.

PMID- 8884240
TI  - Regulation of growth of cultured smooth muscle cells from diabetic rats by
      interleukin-1 beta: role of nitric oxide.
AB  - We examined the influence of streptozotocin-induced diabetes on the growth of
      cultured rat aortic smooth muscle cells in the presence of interleukin-1 beta.
      Interleukin-1 beta induced a dose-dependent biphasic effect on proliferation of
      diabetic and control smooth muscle cells, consistent with the data on
      [3H]thymidine incorporation and cell counts. However, the major effect of
      interleukin-1 beta was to stimulate growth of diabetic cells and inhibit growth
      of control cells. Furthermore, interleukin-1 beta induced a dose-dependent
      increase in nitric oxide (NO) release and in intracellular cyclic GMP
      accumulation: nitrite release was similar in both smooth muscle cell models but
      cyclic GMP accumulation was greater in diabetic cells than in controls. These
      results suggest that the inhibitory loop involving NO is not effective enough to
      completely counterbalance the stimulatory effects of interleukin-1 beta on
      diabetic cells. Therefore, experimental diabetes may modify the interleukin-1
      beta-regulated smooth muscle cell growth.

PMID- 8884241
TI  - The role of protein kinase C in nicotinic responses of bovine chromaffin cells.
AB  - The effects of the protein kinase C inhibitor CGP 41251 (31-benzoyl
      staurosporine) on nicotinic responses of cultured bovine adrenal chromaffin cells
      have been investigated. CGP 41251 inhibited tyrosine hydroxylase activation by
      phorbol 12,13-dibutyrate, with an IC50 of < 0.3 microM and complete inhibition at
      1 microM. In contrast, it had little effect on nicotine-stimulated tyrosine
      hydroxylase activity up to 1 microM, and did not fully inhibit it even at 10
      microM. From 1 to 10 microM, CGP 41251 caused a similar concentration-dependent
      inhibition of tyrosine hydroxylase activity stimulated by nicotine, K+, forskolin
      and 8-Br-cyclic AMP. CGP 42700 (19,31-dibenzoyl-staurosporine), a structural
      analogue of CGP 41251 that lacks activity as a protein kinase C inhibitor, had no
      effect on tyrosine hydroxylase activity stimulated by any of the agonists. CGP
      41251 had no effect on catecholamine secretion induced by nicotine. The results
      suggest phorbol ester-sensitive protein kinase C isozymes do not play a major
      role in nicotinic stimulation of tyrosine hydroxylase activity or catecholamine
      secretion in chromaffin cells.

PMID- 8884242
TI  - Stable expression of homomeric AMPA-selective glutamate receptors in BHK cells.
AB  - cDNAs encoding glutamate receptor glu1, glu2 (Q and R) or glu4 under control of a
      constitutively active metallothionine promoter, were transfected into baby
      hamster kidney cells. Following the addition of selection agent, transfectants
      expressing high levels of glutamate receptor as measured by [3H]alpha-amino-3
      hydroxyl-5-methyl-isoxalazole-4-propionate (AMPA) binding, were selected for
      further studies. Using glutamate receptor antibodies, the receptor proteins were
      visualized in Western blotting as having a molecular weight of approximately 100
      kDa. [3H]AMPA binding to the glutamate receptor expressing cell lines revealed
      that glu1, glu2 (Q), and glu4 receptors displayed a single site in Scatchard
      analysis with Kd values of 12, 15.7 and 21 nM, respectively. However, the Ca2+
      impermeable variant of the glu2 receptor, glu2 (R) displayed a curvilinear
      Scatchard plot. Computer resolution suggested the presence of a high and low
      affinity state (KH = 2.9 nM; KL = 40.7 nM). The pharmacological profile of the
      [3H]AMPA binding to these recombinant receptors resembled the high affinity
      [3H]AMPA binding site in rat brain showing high affinity for glutamate,
      quisqualate, and medium affinity for 6-cyano-7-nitro-quinoxaline-2,3-dione, CNQX;
      6,7-dinitro-quinoxaline-2,3-dione, DNQX; and 6-nitro-7-sulphanyl
      benzo(f)quinoxaline-2,3,dione, NBQX. Kainate displayed low affinity and N-methyl
      D-aspartate (NMDA), was inactive in inhibiting specific [3H]AMPA binding. These
      cell lines will prove to be important tools in the study of glutamate receptors.

PMID- 8884243
TI  - IP3 receptor antagonist heparin uncompetitively inhibits [3H](+)-SKF-10047
      binding to sigma receptors.
AB  - Interaction of sigma receptors with intracellular Ca2+ channel blocker and
      modulators was examined. Ryanodine and inositol 1,4,5-trisphosphate (IP3) did not
      inhibit [3H](+)-N-allylnormetazocine ([3H](+)-SKF-10047) binding to sigma
      receptors from either brain microsomal fractions or liver membrane extracts of
      the rat. However, the IP3 receptor antagonist heparin inhibited [3H](+)-SKF-10047
      to sigma receptors in an uncompetitive manner with a Ki of 93 microM. These
      results suggest that sigma receptors may bear some relationship with IP3 receptor
      associated proteins or channels.

PMID- 8884244
TI  - The mouse vas deferens: a pharmacological preparation sensitive to nociceptin.
AB  - The newly discovered neuropeptide, nociceptin (alias orphanin FQ), was tested for
      its potential direct effects, as well as for its ability to modify the
      electrically evoked contractions in several isolated organs suspended in vitro.
      The electrically stimulated mouse vas deferens is a sensitive preparation on
      which nociceptin exerts an inhibitory effect which is not affected by naloxone.
      The mouse vas deferens is therefore proposed as a bioassay for nociceptin and
      related compounds.

PMID- 8884245
TI  - How to excel as a teacher of geriatrics.

PMID- 8884246
TI  - Abortion article hits a nerve with readers.

PMID- 8884247
TI  - Abortion article hits a nerve with readers.

PMID- 8884248
TI  - Abortion article hits a nerve with readers.

PMID- 8884249
TI  - Entry of US medical school graduates into family practice residencies: 1995-1996
      and 3-year summary.
AB  - This is the 15th report prepared by the American Academy of Family Physicians
      (AAFP) on the percentage of each US medical school's graduates entering family
      practice residency programs. Approximately 14.6% of the 16,124 graduates of US
      medical schools between July 1994 and June 1995 were first-year family practice
      residents in October 1995, compared with 13.4% in 1994 and 12.3% in 1993. This is
      the highest percentage since 1980-1981 (12.8%), when this series of studies
      began. Medical school graduates from publicly funded medical schools were almost
      twice as likely to be first-year family practice residents in October 1995 than
      were residents from privately funded schools, 18% compared with 9.7%. The West
      North Central region reported the highest percentage of medical school graduates
      who were first-year residents in family practice programs in October 1995 at
      24.8%; the Middle Atlantic and New England regions continued with the lowest
      percentages at 7.6% and 9.3%, respectively. Approximately one in two medical
      school graduates (46.7%) entering a family practice residency program as first
      year residents in October 1995 entered a program in the same state where they
      graduated from medical school. The percentages for each medical school have
      varied substantially from year to year since the AAFP began reporting this
      information. The average percentage for each medical school for the last 3 years
      is reported. In addition, the number and percentage of graduates from colleges of
      osteopathic medicine who entered Accreditation Council for Graduate Medical
      Education-accredited family practice residency programs are reported.

PMID- 8884250
TI  - Results of the 1996 National Resident Matching Program: family practice.
AB  - The results of the 1996 National Resident Matching Program (NRMP) set records in
      the number of positions filled in family practice residencies, with a 10.8%
      increase over 1995 (2,840 vs 2,563) and a 9.4% increase in positions filled with
      US seniors (2,276 vs 2,081). This is the largest number of US seniors choosing
      family practice in the history of the NRMP. A total of 196 (6.7%) more positions
      were offered in family practice through the NRMP, compared with 1995 (3,137 vs
      2,941). Thus, 195 of these additional 196 positions were filled with US seniors.
      In keeping with the trend begun in 1992, 242 more positions were filled on July
      1, 1996, than 1995 (3,494 vs 3,252), for a fill rate of 97.8%. Internal medicine
      residencies matched 67 fewer US seniors in 1996, while pediatric residencies
      matched 85 more US seniors. During the past 4 years, family practice has been the
      choice of 82.6% of the additional US seniors choosing a primary care residency.
      With continued record increased interest in family practice as a career choice
      and the need for more family physicians, priority support for the nation's family
      practice residency programs continues to be of critical importance.

PMID- 8884251
TI  - The difficult patient: creation of a curriculum by third-year family practice
      residents.
AB  - BACKGROUND AND OBJECTIVES: Family practice residents tend to perceive
      psychosocial problems as less important than other factual aspects of their
      curriculum. To address this, we developed a problem-based learning (PBL) approach
      to the biopsychosocial model of medical care. METHODS: Third-year residents
      presented current problematic patients at a PBL advanced psychiatry conference.
      Data were collected on topics generated, resident attendance, and conference
      evaluation. RESULTS: The residents generated a topic list that closely matched a
      prior faculty-generated list. Some topics were discussed on multiple occasions;
      others not on the faculty list were also generated. Topics omitted were mental
      health in the physician's home, crisis prevention/intervention, and troubled
      marriages. In 1992-1995, resident attendance ranged from 56%-79%. A minority (0-5
      residents) consistently attended fewer than 50% of the conferences. Residents
      evaluated the conference from "good" to "very good." CONCLUSIONS: By employing a
      PBL format and allowing residents to present current patients, conferences were
      better attended and covered almost all topics previously identified as important.
      PBL promoted efficient use of residents' time since residents were only required
      to research the literature about group knowledge deficits. This provided good
      training for the residents and excellent continuing medical education for
      faculty.

PMID- 8884252
TI  - How required US family medicine clerkships and preceptorships evaluate medical
      students.
AB  - BACKGROUND: Despite the increasing representation of family medicine among
      required clinical experiences in medical school, relatively little has been
      written about how students are evaluated on these experiences. This survey
      reports on evaluation methods used on US family medicine clerkships/
      preceptorships and educator satisfaction with these methods. METHODS: Information
      was obtained by a survey mailed to the directors of all required allopathic
      family medicine clinical rotations (n = 69). RESULTS: Ninety-one percent of sites
      contacted returned the survey. Forty-seven percent of family medicine required
      clinical rotations are 6 weeks or longer, and 71% occur in the third year of
      medical school. The clinical grade contributes an average of 60% to the final
      grade, while other assignments contribute 21% to the grade. Fifty-two percent of
      respondents indicated "moderate or less" overall satisfaction with their current
      evaluation methodologies. CONCLUSIONS: Among institutions with required family
      medicine clerkships/preceptorships, this survey documents a trend toward these
      experiences occurring in the third year of medical school and lasting 6 weeks or
      more. In addition to traditional evaluation methodologies, other assignments
      contribute substantially to the overall grade on required family medicine
      rotations. The overall lack of satisfaction with current evaluation methodologies
      highlights the need for information sharing and networking among those who
      develop and implement evaluation methods on family medicine clerkships and
      preceptorships.

PMID- 8884253
TI  - The role of office-based procedures in family practice residency training.
AB  - BACKGROUND: Fifteen years ago, the American Board of Family Practice determined
      the need for a procedural "core" list requirement for residency training. Program
      directors at that time could not reach a consensus about a specific list of
      procedures. This study examined the current attitudes of residency directors
      about a core list of office-based procedures required for residency training.
      METHODS: A questionnaire was designed to elicit general information about
      attitudes toward establishing a core requirement of office-based procedures. The
      program directors were asked to select from a list of 35 office-based procedures
      those they felt should be required. The questionnaire was mailed to all 421 US
      family practice residency directors. RESULTS: The response rate was 78%. Of
      responding directors, 68% favored a core list requirement. Eleven out of 35
      procedures received at least 80% consensus by those directors favoring a core
      list requirement. Programs situated in rural areas were more likely to oppose the
      core list requirement. Geographic region of the residency program impacted on the
      number of core procedures respondents felt residents should master in their
      training. CONCLUSIONS: The majority of residency directors who responded believe
      that the potential advantages of a core list requirement outweigh the potential
      disadvantages. The directors approximated consensus (80% agreement) on seven
      procedures across all geographic regions. With this evidence in mind, it would
      seem appropriate for the governing bodies of family practice to reexamine the
      core procedure issue.

PMID- 8884254
TI  - Student and faculty collaboration in a clinic for the medically underserved.
AB  - BACKGROUND AND OBJECTIVES: Growing numbers of uninsured and underinsured
      individuals in the United States have resulted in increased needs for health care
      for medically underserved populations. Educational strategies are needed that
      provide opportunities for students to develop the attitudes, knowledge, and
      skills necessary for providing quality health care for underserved patients.
      METHODS: Medical students, residents, and faculty of the University of Wisconsin
      Madison Medical School worked together to establish extracurricular opportunities
      for first- and second-year students to participate in medical clinics serving the
      poor and homeless. The process for the development and operation of a volunteer
      clinic is described. RESULTS: In the last 2 years, 163 medical students, 27
      residents, and 21 faculty have provided care to more than 1,000 patients.
      Patients, students, residents, and faculty reported high satisfaction with the
      experience. CONCLUSIONS: Medical students, residents, and faculty working in
      collaboration can provide increased access to care for the medically underserved.
      Engaging in community-oriented primary health care early in their medical
      education provided positive learning opportunities for medical students,
      especially those interested in generalist careers.

PMID- 8884255
TI  - Adolescent life experiences of physicians in primary care compared with other
      specialties.
AB  - BACKGROUND AND OBJECTIVES: The perceived need for more primary care physicians
      has stimulated several studies of specialty choice. One study that used a cross
      sectional design found that life-history experiences differentiated between
      generalist and specialist physicians. The present study assessed whether life
      history experiences reported during college could differentiate between
      physicians currently in primary care versus other specialties. METHODS: We
      tracked students who completed a 118-item inventory of life history experiences
      (biodata) during their freshman orientation at a large, public university and who
      subsequently graduated from the state's largest medical school. We compared
      biodata responses of those currently practicing in primary care with those in
      other specialties. RESULTS: Biodata and medical specialty information were
      available for 169 physicians, of which 145 were men (27 primary care, 118 other
      specialties), and 24 women (three primary care, 21 other specialties). Women were
      excluded from further analyses. Using 13 biodata factors identified in prior
      studies, primary care physicians had lower scores on "orientation toward
      academics," and higher scores on "personal and social adjustment." Biodata
      accounted for 19% of the variance in specialty choice. CONCLUSIONS: Biodata can
      help identify medical school applicants who will have a greater likelihood of
      selecting a primary care specialty.

PMID- 8884256
TI  - Use of wet mount to predict Chlamydia trachomatis and Neisseria gonorrhea
      cervicitis in primary care.
AB  - BACKGROUND AND OBJECTIVES: Cervicitis is associated with salpingitis,
      infertility, and complications of pregnancy. Universal screening has been
      recommended for high-prevalence populations but may not be appropriate in the
      family practice setting. Leukocytes on an endocervical gram stain have been
      associated with infectious cervicitis due to Chlamydia trachomatis and Neisseria
      gonorrhea. This study sought to determine whether the finding of leukocytes in a
      vaginal wet mount could be used to screen for infectious cervicitis in an urban
      family practice. METHODS: A consecutive sample of 357 women had cultures for C
      trachomatis and N gonorrhea and a standardized wet mount. RESULTS: All women with
      infectious cervicitis were under age 35. Thirty-six percent of infected women had
      more leukocytes than epithelial cells in the wet mount, compared with 23% of
      women without these organisms. CONCLUSIONS: Wet mount findings did not reliably
      predict infectious cervicitis. Study of a larger population is needed to confirm
      these findings.

PMID- 8884257
TI  - Twelve years and a valley later.

PMID- 8884258
TI  - The medical student's perspective on community rotations.

PMID- 8884259
TI  - Anyone who is here to treat illness should leave now.

PMID- 8884260
TI  - Identification and characterization of a cDNA and the structural gene encoding
      the mouse epithelial membrane protein-1.
AB  - The PMP22/EMP/MP20 gene family includes four closely related proteins, peripheral
      myelin protein-22 (PMP22), epithelial membrane protein-1 (EMP-1), epithelial
      membrane protein-2 (EMP-2), and epithelial membrane protein-3 (EMP-3), which
      share amino acid identities ranging from 33 to 43%. In addition, the lens
      specific membrane protein MP20 represents a more distant relative. Functionally,
      this family of proteins is likely to play important roles in the control of cell
      proliferation, cell differentiation, and cell death. In particular, mutations
      affecting the PMP22 gene are responsible for various hereditary peripheral
      neuropathies in humans and mice. We report the isolation and characterization of
      a mouse EMP-1 cDNA and the corresponding emp-1 gene. Mouse EMP-1 displays 93%
      amino acid identity to rat EMP-1 and 39% identity to mouse PMP22. The cDNA
      predicted EMP-1 protein contains four putative membrane-associated domains and
      can be N-linked glycosylated in vitro. EMP-1 is encoded by a single-copy gene
      with the positions of introns exactly conserved between emp-1 and PMP22,
      corroborating the hypothesis that both genes belong to the same family. Computer
      predicted structural domains of EMP-1 are partially mirrored by the exon/intron
      structure of emp-1. Most interestingly, exon 4, which covers the potential second
      transmembrane domain, a small intracellular loop, and half of the third
      transmembrane domain, encodes the most highly conserved regions between the EMP-1
      and PMP22 proteins and is also remarkably conserved in the MP20 gene, indicating
      some shared functional significance for this module in the PMP22/EMP/MP20 family.

PMID- 8884261
TI  - Overall informativity, OI, in DNA polymorphisms revealed by inter-Alu PCR:
      detection of genomic rearrangements.
AB  - We studied two systems of multilocus markers revealed by PCR using primers
      directing amplification between Alu repeats in a tail-to-tail orientation.
      Genomic polymorphisms were detected as the presence or absence of the
      electrophoretic bands representing DNA fragments of a given length. A total of
      104 such fragments segregating as Mendelian markers in a panel of eight CEPH
      families were analyzed by two-point linkage analysis. Fifty-one of these
      fragments were localized with respect to CEPH markers; they represented 33 loci,
      7 of which were multiallelic. Locus-specific oligonucleotides were developed and
      used as hybridization probes to identify the mapped loci within a complex pattern
      of inter-Alu PCR products. A great proportion of inter-Alu PCR polymorphisms
      represented length variants within amplified DNA segments, while others were
      presumably due to mutations within the priming sites. To describe the expected
      number of informative loci per typing experiment we introduced a parameter called
      overall informativity (OI), which provides a single measure of the multiplex
      ratio and the informativity of markers contributing to a multilocus system (OI of
      a single locus is equivalent to its heterozygosity and cannot exceed 0.5 for a
      biallelic codominant marker). High OI values (5.8 and 11.5) of the two presented
      systems of inter-Alu PCR markers of random chromosomal distribution render them
      suitable for mapping genomic rearrangements such as genomic deletions in tumoral
      tissues. This was illustrated by the detection of loss of heterozygosity in the
      9q22-qter region in sporadic colon cancer.

PMID- 8884262
TI  - Construction of a YAC contig covering human chromosome 6p22.
AB  - A contig covering human chromosome 6p22 that consists of 134 YAC clones aligned
      based on the presence/absence of 52 DNA markers is presented. This contig
      overlaps with the 6p23 contig at its telomeric end and with the 6p21.3 contig at
      its centromeric end. The order of loci within the contig resolves the relative
      positions of several genetically mapped markers. Among the additional markers
      used here, there are eight novel PCR assays. The 12 known genes and anonymous
      ESTs located within the contig establish a first step toward a transcriptional
      map of this region. The instability of YAC clones observed during this work is
      also discussed.

PMID- 8884263
TI  - Human uracil-DNA glycosylase gene: sequence organization, methylation pattern,
      and mapping to chromosome 12q23-q24.1.
AB  - The human uracil-DNA glycosylase gene (UNG) spans approximately 13.5 kb including
      the promoter. UNG comprises 6 exons and 5 introns and was assigned to chromosome
      12q23-q24.1 by radiation hybrid mapping. UNG exhibits typical features of
      housekeeping genes, including a 5' CpG island of 1.2 kb and a very GC-rich TATA
      less promoter containing a number of elements involved in constitutive expression
      and cell cycle regulation. A smaller CpG island is located just downstream of the
      gene. Within the 15-kb sequence we identified 16 Alu retroposons, 2 of which
      contain putative competent RNA polymerase III promoters, 3 copies of medium
      reiteration frequency repeats, and 1 copy of a mammalian-wide interspersed
      repetitive element, as well as a 300-bp TA-dinucleotide repeat. In vitro
      methylation of the UNG promoter strongly reduced promoter activity, but
      methylation may not be involved in regulation of UNG in vivo since a narrow
      region of the 5' CpG island comprising the putative transcription factor binding
      region appears to be invariably methylation-free.

PMID- 8884264
TI  - ZOO-FISH suggests a complete homology between human and capuchin monkey
      (Platyrrhini) euchromatin.
AB  - Chromosome comparisons using in situ hybridization of all human chromosome
      specific libraries on Capuchin monkey (Cebus capucinus, Cebidae, Platyrrhini)
      metaphases were performed with a new technique simultaneously revealing a G
      banding and chromosome "painting." A complete homology between human (HSA) and C.
      capucinus (CCA) chromosomes was demonstrated, except for constitutive
      heterochromatin. Eleven C. capucinus chromosomes are homologous to 11 human
      chromosomes: CCA 2 = HSA 4; CCA 3 = HSA 6; CCA 12 = HSA 9; CCA 16 = HSA 11; CCA
      10 = HSA 12; CCA 11 = HSA 13; CCA 20 = HSA 17; CCA 8 = HSA 19; CCA 23 = HSA 20;
      CCA 24 = HSA 22; and CCA X = HSA X. Ten C. capucinus chromosomes are homologous
      to parts of human chromosomes: CCA 13 = HSA 8q; CCA 14 = HSA 2q; CCA 15 = HSA 1p
      + 1q proximal; CCA 17 = HSA 7 part; CCA 18 and 19 = HSA 3 part; CCA 21 and 22 =
      HSA 1q distal; CCA 25 = HSA 10p; and CCA 26 = HSA 15q part. Six C. capucinus
      chromosomes are homologous to parts of two human chromosomes: CCA 1 = HSA 5 + 7
      part; CCA 4 = HSA 2p + q proximal + 16q; CCA 5 = HSA 10q + 16p; CCA 6 = HSA 14 +
      15 part; CCA 7 = HSA 8p + 18; and CCA 9 = HSA 3 part + 21. Many previous banding
      comparisons were confirmed but several cryptic or complex rearrangements could be
      identified. With the C. capucinus karyotype having been shown to be fairly
      ancestral, this comparison opens the possibility to compare human chromosomes to
      most Cebidae species.

PMID- 8884265
TI  - Primary structure of human 11-cis retinol dehydrogenase and organization and
      chromosomal localization of the corresponding gene.
AB  - The universal chromophore of visual pigments in higher animals is 11-cis
      retinaldehyde. The final step in the biosynthetic pathway generating this
      compound is catalyzed by 11-cis retinol dehydrogenase, a membrane-bound enzyme
      abundantly expressed in the retinal pigment epithelium of the eye. In this work
      we demonstrate that the primary structure of human 11-cis retinol dehydrogenase
      is highly conserved with 91% identity to the bovine enzyme. The gene encoding 11
      cis retinol dehydrogenase spans over approximately 4.1 kb of DNA and is divided
      into four translated exons. Analysis of a panel of somatic cells hybrids and
      fluorescence in situ hybridization on metaphase chromosomes revealed that the
      gene is located on chromosome 12q13-q14. Due to the unique role of 11-cis retinol
      dehydrogenase in the generation of visual pigments, it is a candidate gene for
      involvement in hereditary eye disease.

PMID- 8884266
TI  - Mapping of unconventional myosins in mouse and human.
AB  - Myosins are molecular motors that move along filamentous actin. Seven classes of
      myosin are expressed in vertebrates: conventional myosin, or myosin-II, as well
      as the 6 unconventional myosin classes-I, -V, -VI, -VII, -IX, and -X. We have
      mapped in mouse 22 probes encompassing all known unconventional myosins and, as a
      result, have identified 16 potential unconventional myosin genes. These genes
      include 7 myosins-I, 2 myosins-V, 1 myosin-VI, 3 myosins-VII, 2 myosins-IX, and 1
      myosin-X. The map location of 5 of these genes was identified in human
      chromosomes by fluorescence in situ hybridization.

PMID- 8884267
TI  - Molecular cloning and domain structure of human myosin-VIIa, the gene product
      defective in Usher syndrome 1B.
AB  - Myosin-VIIa is an unconventional myosin with relatively restricted expression.
      Cloned first from an intestinal epithelium cell line, it occurs most notably in
      the testis, in the receptor cells of the inner ear, and in the pigment epithelium
      of the retina. Defects in myosin-VIIa cause the shaker-1 phenotype in mice and
      Usher syndrome 1B in human, which are characterized by deafness, lack of
      vestibular function, and (in human) progressive retinal degeneration. Because the
      described cDNAs encode less than half of the protein predicted from immunoblots,
      we have cloned cDNAs encoding the rest of human myosin-VIIa. Two transcripts were
      found, one encoding the predicted 250-kDa protein and another encoding a shorter
      form. Both transcripts were found in highest abundance in testis, although the
      shorter transcript was much less abundant. Both could be detected in lymphocytes
      by RT-PCR. The myosin tail encoded by the long transcript includes a long repeat
      of approximately 460 amino acids. Each repeat contains a novel "MyTH4" domain
      similar to domains in three other myosins, and a domain similar to the membrane
      associated portion of talin and other members of the band-4.1 family.

PMID- 8884268
TI  - Cloning and characterization of the human mitochondrial DNA polymerase, DNA
      polymerase gamma.
AB  - The nuclear-encoded DNA polymerase gamma (DNA POL gamma) is the sole DNA
      polymerase required for the replication of the mitochondrial DNA. We have cloned
      the cDNA for human DNA POL gamma and have mapped the gene to the chromosomal
      location 15q24. Additionally, the DNA POL gamma gene from Drosophila melanogaster
      and a partial cDNA for DNA POL gamma from Gallus gallus have been cloned. The
      predicted human DNA POL gamma polypeptide is 1239 amino acids, with a calculated
      molecular mass of 139.5 kDa. The human amino acid sequence is 41.6, 43.0, 48.7,
      and 77.6% identical to those of Schizosaccharomyces pombe, Saccharomyces
      cerevisiae, Drosophila melanogaster, and the C-terminal half of G. gallus,
      respectively. Polyclonal antibodies raised against the polymerase portion of the
      protein reacted specifically with a 140-kDa protein in mitochondrial extracts and
      immunoprecipitated a protein with DNA POL gamma like activity from mitochondrial
      extracts. The human DNA POL gamma is unique in that the first exon of the gene
      contains a CAG10 trinucleotide repeat.

PMID- 8884269
TI  - Direct complementation of Chlamydomonas mutants with amplified YAC DNA.
AB  - We previously described the construction and characterization of a Chlamydomonas
      genomic library in yeast artificial chromosomes (YACs). Here we describe the
      isolation and genetic mapping of YACs at the FLA10 locus on the uni chromosome as
      well as isolation of a YAC spanning the PF14 locus on chromosome VI. Genetic
      mapping of YAC end clones by RFLP analyses in interspecific crosses reveals that
      YACs with a physical size of 150 kb commonly span genetic intervals defined by
      one or two recombination events in crosses of approximately 20 tetrads. This
      promises to make chromosomal walking in Chlamydomonas a relatively efficient
      enterprise. We also describe our development of a method for direct
      complementation of mutant genes by transformation with amplified wildtype YAC
      DNA. The use of positional cloning using YACs and this direct functional assay
      for the presence of a gene in a YAC represent powerful molecular genetic tools
      enabling the cloning of most any Chlamydomonas gene.

PMID- 8884270
TI  - A point mutation creating an extra N-glycosylation site in fibrillin-1 results in
      neonatal Marfan syndrome.
AB  - Fibrillin-1 is a large cysteine-rich glycoprotein of the 10-nm microfibrils in
      the extracellular matrix. A spectrum of mutations in the fibrillin-1 gene (FBN1)
      have been identified in patients with Marfan syndrome (MFS), and the majority of
      mutations resulting in the neonatal and often lethal form of MFS have been
      identified in the restricted region of exons 24-32 of the FBN1 gene. Here we
      report a novel point mutation in exon 25 of the FBN1 gene in a patient with
      lethal MFS. The mutation resulted in a molecular defect rarely encountered in
      human diseases, the creation of an extra consensus sequence for N-glycosylation.
      Metabolic labeling of the patient fibroblast culture and in vitro expression of
      the mutagenized cDNA construct suggest that this novel N-glycosylation site is
      actually utilized. Immunohistochemical and ultrastructural analyses of the
      fibroblast cultures of the patient show that this excessive N-glycosylation
      severely affects microfibril formation in vitro; this finding emphasizes the
      importance of correct posttranslational modifications of fibrillin molecules for
      correct aggregation into microfibrillar structures.

PMID- 8884271
TI  - Characterization of the cDNA and gene encoding human PDE3B, the cGIP1 isoform of
      the human cyclic GMP-inhibited cyclic nucleotide phosphodiesterase family.
AB  - Two distinct PDE3 [cyclic GMP-inhibited cyclic nucleotide phosphodiesterase (cGI
      PDE)] isoforms, cGIP1 and cGIP2, have been identified. Here we report cloning of
      the cDNA and gene encoding human (H)cGIP1 (classified as PDE3B). The cDNA encodes
      a protein of 1112 amino acids (approximately 123 kDa). Northern blots indicate
      that its mRNA is expressed in several adipose tissue depots. The human PDE3B gene
      is composed of 16 exons spanning more than 114 kb and was localized to chromosome
      11p15 by in situ hybridization. Exon/intron boundaries were determined, and
      genetic polymorphism, confirmed by single-strand conformational polymorphism of
      DNA from 25 healthy subjects, was demonstrated in exon 4 at nucleotide 1389
      (A/G). Two polymorphic dinucleotide repeat sequences were identified in introns 5
      and 12.

PMID- 8884272
TI  - Isolation of the ATP-binding human homolog of the arsA component of the bacterial
      arsenite transporter.
AB  - Arsenite resistance in bacteria is mediated by an efflux pump composed of the
      arsA and arsB gene products. We have isolated the human homolog of the bacterial
      arsA (hARSA-I), a member of the ATPase superfamily with no transmembrane domain.
      Southern and Northern analyses indicated the presence of two cross-hybridizing
      genes in the human genome and expression of hARSA-I in many tissues. A rabbit
      antiserum raised against a glutathione-S-transferase (GST)/hARSA-I fusion protein
      identified two cross-reacting proteins of 37 and 42 kDa by Western analysis in
      two different human cell lines. Overexpression of hARSA-I in the embryonal human
      kidney 293 cell line was accompanied by overproduction of the 37-kDa protein
      Biochemical analysis using the GST/hARSA-I fusion protein indicated that hARSA-I
      is an ATPase analogous to the bacterial ArsA. Thus, hARSA-I is a new eukaryotic
      member of a highly conserved ATP-binding superfamily of proteins.

PMID- 8884273
TI  - Mapping human telomere regions with YAC and P1 clones: chromosome-specific
      markers for 27 telomeres including 149 STSs and 24 polymorphisms for 14
      proterminal regions.
AB  - A YAC library enriched for telomere clones was constructed and screened for the
      human telomere-specific repeat sequence (TTAGGG). Altogether 196 TYAC library
      clones were studied: 189 new TYAC clones were isolated, 149 STSs were developed
      for 132 different TY-ACs, and 39 P1 clones were identified using 19 STSs from 16
      of the TYACs. A combination of mapping methods including fluorescence in situ
      hybridization, somatic cell hybrid panels, clamped homogeneous electric fields,
      meiotic linkage, and BLASTN sequence analysis was utilized to characterize the
      resource. Forty-five of the TYACs map to 31 specific telomere regions. Twenty
      four linkage markers were developed and mapped within 14 proterminal regions (12
      telomeres and 2 terminal bands). The polymorphic markers include 12
      microsatellites for 10 telomeres (1q, 2p, 6q, 7q, 10p, 10q, 13q, 14q, 18p, 22q)
      and the terminal bands of 11q and 12p. Twelve RFLP markers were identified and
      meiotically mapped to the telomeres of 2q, 7q, 8p, and 14q. Chromosome-specific
      STSs for 27 telomeres were identified from the 196 TYACs. More than 30,000
      nucleotides derived from the TYAC vector-insert junction regions or from regions
      flanking TYAC microsatellites were compared to reported sequences using BLASTN.
      In addition to identifying homology with previously reported telomere sequences
      and human repeat elements, gene sequences and a number of ESTs were found to be
      highly homologous to the TYAC sequences. These genes include human coagulation
      factor V (F5), Weel protein tyrosine kinase (WEE1), neurotropic protein tyrosine
      kinase type 2 (NTRE2), glutathione S-transferase (GST1), and beta tubulin (TUBB).
      The TYAC/P1 resource, derivative STSs, and polymorphisms constitute an enabling
      resource to further studies of telomere structure and function and a means for
      physical and genetic map integration and closure.

PMID- 8884274
TI  - Refinement of the Van der Woude gene location and construction of a 3.5-Mb YAC
      contig and STS map spanning the critical region in 1q32-q41.
AB  - Van der Woude syndrome (VWS) is the most frequent form of syndromic clefting.
      Linkage analysis has localized the gene between D1S245 and D1S414, an interval of
      4.1 cM with the following order of loci: centromere-D1S245/D1S471-D1S491-D1S205
      D1S414 -telomere. A microdeletion around D1S205 aided in narrowing the critical
      region to D1S491-D1S414 by heterozygosity testing. In this study, the location
      was refined by detection of a recombinant with D1S205 in a new family, indicating
      that VWS lies between D1S491 and D1S205, a 1.6-cM interval. A roughly 3.5-Mb YAC
      contig was built from D1S245 through D1S414, encompassing the interval D1S491
      D1S205 in level 1 or level 2 paths. Clones were assembled by sequence tagged site
      (STS) content using the five polymorphic markers from above, four novel STSs
      identified from YAC ends, and a new STS derived from probe CRI-L461 (D1S70).
      D1S70 was assigned to the critical region. One single YAC, yCEPH785B2, contains
      both flanking STSs (D1S491, D1S205). STS content mapping suggests neither
      chimerism nor deletion of yCEPH785B2 but does suggest that the maximum size of
      the critical region is approximately 850 kb. All STSs were tested for their
      presence on a somatic cell hybrid containing the microdeleted chromosome 1 as the
      sole human chromosome 1 component. Both the proximal and distal ends of the
      microdeletion mapped to the 850-kb YAC, yCEPH785B2. Therefore, the microdeletion
      overlapped the critical region, confirming the genetic recombinant data.

PMID- 8884275
TI  - Cloning and characterization of the human lectin P35 gene and its related gene.
AB  - We previously cloned a novel human lectin, designated P35, with both collagen
      like and fibrinogen-like domains. P35 recognizes GlcNAc residues and is opsonic
      toward microorganisms. The overall structure of P35 closely resembles those of
      two pig ficolins that are putative TGF-beta 1-binding proteins. In this study, we
      analyzed the exon-intron structure and chromosomal location of the P35 gene as
      well as its structural relationship to splicing variants. In addition, we
      isolated another distinct genomic clone corresponding to the upstream region of a
      P35-related gene that has an exon organization closely resembling that of the P35
      gene. The sequences of exons in the P35-related gene were identical to the cDNA
      sequence reported for "human ficolin." Northern blotting revealed that the P35
      gene is expressed mainly in liver, whereas the P35-related gene is expressed in
      lung and peripheral blood leukocytes, demonstrating tissue-specific expression of
      these two genes. Both genes were assigned to a closely related region of
      chromosome 9 at 9q34.

PMID- 8884276
TI  - The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1
      CMKBR5) are clustered in the p21.3-p24 region of chromosome 3.
AB  - The five human CC-chemokine receptors functionally characterized to date were
      mapped by using a radiation hybrid panel and YAC contigs. The genes encoding CC
      CKR1, CC-CKR2, CC-CKR3, and CC-CKR5 (designated respectively CMKBR1, CMKBR2,
      CMKBR3, and CMKBR5 in the Genome Data Bank) were found to be clustered in the
      3p21.3 region of chromosome 3, between the AFM362WB9 and the WI-6983 markers. The
      four genes fall within a total distance of about 350 kb. The fifth gene (CMKBR4,
      encoding the CC-CKR4 receptor) was located more distally (3p24) on the same
      chromosome, between the FB18G7 and the D3S1768 markers. These localizations were
      confirmed by mapping the genes into the YAC contigs covering these regions. The
      clustering of chemokine receptor genes suggests a relatively recent expansion of
      the gene family by gene duplication. Deletions and duplications of the 3p21
      region have been described in neoplastic disorders of the hematopoietic lineage,
      suggesting a potential link with the CC-chemokine receptor gene family.

PMID- 8884277
TI  - Localization of a human double-stranded RNA-binding protein gene (STAU) to band
      20q13.1 by fluorescence in situ hybridization.
AB  - Asymmetric transport of mRNA within the cells is mediated by RNA-binding proteins
      that form, along with the mRNAs and perhaps other small RNAs, stable
      ribonucleoprotein complexes. However, the nature of the protein components of
      these complexes in vertebrates is still unknown. In Drosophila, genetic studies
      have identified a number of potential genes that are necessary for localization
      of mRNAs in oocytes; one of the most studied is the staufen gene. The staufen
      protein has been shown to bind to localized mRNAs in oocytes and to be expressed
      in somatic cells as well. To understand the mechanism of mRNA transport in
      mammals and characterize its components, we recently cloned and sequenced the
      human staufen homolog cDNA (HGMW-approved symbol STAU). In this paper, we show
      that the gene is unique in the human genome and report its chromosomal
      localization by fluorescence in situ hybridization. The human staufen gene maps
      to chromosome 20q13.1, a region that is associated with certain genetic diseases.

PMID- 8884279
TI  - The gene encoding the catalytic subunit C alpha of cAMP-dependent protein kinase
      (locus PRKACA) localizes to human chromosome region 19p13.1.
AB  - We have determined the chromosomal localization of the gene for the catalytic
      subunit C alpha of cAMP-dependent protein kinase (locus PRKACA) to human
      chromosome 19 using polymerase chain reaction (PCR) and Southern blot analysis of
      two different somatic cell hybrid mapping panels. In addition, PCR analysis of a
      chromosome 19 mapping panel revealed the presence of a human C alpha-specific
      amplification product only in cell lines containing the region 19p13.1 to 19q12.
      Finally, two-color fluorescence in situ hybridization to metaphase chromosomes
      using the human C alpha cDNA and human chromosome 19 inter-Alu-PCR product as
      probes localized the human C alpha gene to chromosome region 19p13.1.

PMID- 8884278
TI  - Isolation, mapping, and functional expression of the mouse X chromosome glycerol
      kinase gene.
AB  - Glycerol kinase (Gyk) participates in the metabolism of endogenously derived and
      dietary glycerol. Deficiency of the human enzyme activity is an X-linked
      recessive disorder with a clinical picture varying from childhood metabolic
      crisis to asymptomatic adults incidentally identified by hyperlipidemia screening
      (pseudohypertriglyceridemia). Gyk is a member of a small group of kinases termed
      ambiquitous enzymes that are found in the cytosol or as membrane-bound enzymes
      associated with the voltage-dependent anion channel of the mitochondrial outer
      membrane. It was recently reported that in humans there are X-linked and
      autosomal copies of Gyk sequences, both apparently functional genes and processed
      pseudogenes. To understand the role of Gyk in normal metabolism and the variable
      clinical features seen with Gyk deficiency, we have characterized the mouse Gyk
      gene. We present the sequence of a full-length mouse Gyk cDNA that is
      alternatively spliced in brain. The Gyk gene was mapped to the mouse X chromosome
      by both fluorescence in situ hybridization and an interspecies backcross panel,
      demonstrating conservation of synteny with dmd. To confirm the functional
      identity of the cDNA, transient transfection of the cDNA into COS7 cells was
      shown to cause a marked elevation in glycerol kinase activity.

PMID- 8884280
TI  - Genomic imprinting and chromosomal localization of the human MEST gene.
AB  - We have isolated a human homologue (MEST) of the mouse mesoderm-specific
      transcript (Mest) gene that shares about 70% nucleotide sequence homology.
      Northern blot analysis showed that the MEST gene was expressed in all major fetal
      organs and tissues so far examined, i.e., amnion, brain, heart, lung, stomach,
      gut, adrenal, kidney, muscle, and liver, which does not contradict with mesoderm
      specific expression. MEST was abundantly expressed in hydatidiform moles of
      androgenetic origin, whereas it was barely detectable in dermoid cysts of
      parthenogenetic origin. Thus, it seems likely that the MEST gene, mapped to 7q32
      by fluorescence in situ hybridization, is maternally repressed as the mouse
      homologue.

PMID- 8884282
TI  - The high growth (hg) locus maps to a deletion in mouse chromosome 10.
AB  - The high growth (hg) locus in mice produces a 30-50% increase in weight gain of
      homozygous individuals. Here we report that the microsatellite marker D10Mit69 is
      deleted in high growth mice. The deletion of D10Mit69 was uncovered in a screen
      of the high growth mouse and its progenitor strains for available markers in the
      hg region. We demonstrate that hg and D10Mit69 cosegregate in a cross of congenic
      strains C57BL/6J-hghg x C57BL/6J. These results suggest that deletion of a region
      around D10Mit69 is responsible for the high growth effect. Marker D10Mit69 will
      be utilized as an entry point to physical cloning of the hg-containing segment. A
      dense map of markers around hg constructed here should allow identification of
      markers in homologous regions in domestic animals and humans, which may be
      utilized to assess the role of the hg locus in these other species.

PMID- 8884281
TI  - Mouse and human neuronal pentraxin 1 (NPTX1): conservation, genomic structure,
      and chromosomal localization.
AB  - We have previously identified novel members of the pentraxin family (neuronal
      pentraxin 1 and 2) that are expressed in the nervous system. Neuronal pentraxin 1
      (NP1) was identified as a rat protein that may mediate the uptake of synaptic
      material and the presynaptic snake venom toxin, taipoxin. NP2 was identified as a
      separate gene discovered by screening for a human homolog for NP1. Here, we
      report human cDNA and mouse genomic DNA sequences for NP1 (gene symbol NPTX1).
      Human NP1 and mouse NP1 show 95 and 99% amino acid identity, respectively, with
      rat NP1 and conserve all potential glycosylation sites. Like rat NP1, human NP1
      message is large (6.5 kb) and is exclusively localized to the nervous system. The
      mouse NP1 gene is 13 kb in length and contains four introns that break the coding
      sequence of NP1 in the same positions as the introns of the human NP2 gene. The
      human and mouse NP1 genes are localized to chromosome 17q25.1-q25.2 and
      chromosome 11e2-e1.3, respectively. These data demonstrate the existence of a
      separate family of pentraxin proteins that are expressed in the human brain and
      other tissues and that may play important roles in the uptake of extracellular
      material.

PMID- 8884283
TI  - Human selenoprotein P gene maps to 5q31.

PMID- 8884284
TI  - Assignment of the human syntaxin 1B gene (STX) to chromosome 16p11.2 by
      fluorescence in situ hybridization.

PMID- 8884285
TI  - Mapping of rupture of lens cataract (rlc) on mouse chromosome 14.

PMID- 8884286
TI  - Structure and physical mapping of DR1, a TATA-binding protein-associated
      phosphoprotein gene, to chromosome 1p22.1 and its exclusion in Stargardt disease
      (STGD).

PMID- 8884287
TI  - Localization of the gene (TAF2D) encoding the 100-kDa subunit (hTAFII100) of the
      human TFIID complex to chromosome 10 band q24-q25.2.

PMID- 8884288
TI  - The Sry-related gene Sox18 maps to distal mouse chromosome 2.

PMID- 8884289
TI  - Mapping of the human homologue (ORC1L) of the yeast origin recognition complex
      subunit 1 gene to chromosome band 1p32.

PMID- 8884290
TI  - Percutaneous metallic self-expandable endoprostheses in biliary obstruction
      caused by metastatic cancer.
AB  - BACKGROUND/AIMS: Up to now, all reports about metallic stents concerned mostly
      patients with obstructive jaundice due to primary cancer although some of these
      series included a small number of patients with metastatic disease as a cause of
      occlusion of the bile ducts. The question of whether they should be used in
      patients with biliary obstruction due to metastatic disease, and consequently
      have a limited life expectancy, is investigated. PATIENTS AND METHODS: Between
      January 1994 and April 1995, we inserted percutaneously 20 metallic self
      expandable endoprostheses in 14 patients with obstructive jaundice due to
      metastatic disease. RESULTS: Twelve patients died with a mean survival of 144.6
      (range 25-338) days without any evidence of biliary reobstruction. For 2
      patients, we have followup no longer than 30 days. Thirty day mortality was 7.2%
      (1/14). Jaundice reoccurred in one patient but wasn't related to stent
      obstruction, and he died during the first 30 days. We had 2 cases with moderate
      hemobilia. CONCLUSION: We believe that the use of metal stents in patients with
      obstructive jaundice due to metastatic disease is justified. Their high initial
      cost is offset by their prolong patency, decreased complication rate and shorter
      hospitalization.

PMID- 8884291
TI  - Quantitative assessment of severity of biliary tract infection.
AB  - BACKGROUND/AIMS: It is very important for physicians to evaluate the severity of
      the biliary infection. At the moment, there is no useful quantitative system. In
      this study, we propose a scoring system for assessing the severity of biliary
      infections and evaluation of the efficacy of antibacterial and endoscopic
      treatments. MATERIALS AND METHODS: We created a biliary tract infection score
      (BTIS) including local physical and ultrasound findings, signs of inflammation
      and hepatobiliary involvement. The BTIS was calculated in 317 patients: group I
      155 pts with cholecystitis and cholangitis, treated only by antibiotics and group
      II-162 pts with acute cholangitis treated by endoscopic procedures. RESULTS: The
      BTIS allowed the differentiation of the severity of biliary infections: 15.50 +/-
      0.52 in acute cholangitis group and 5.77 +/- 2.79 in group I (p < 0.001). The
      BTIS significantly decreased after antibacterial therapy (excluding only the
      cefotiam subgroup) and in endoscopicaly treated patients. CONCLUSIONS: The BTIS
      is a combination of simple, reliable, acceptable and low cost parameters,
      reflecting the principal pathological processes and degree of abnormalities. A
      BTIS facilitated the assessment of severity of biliary infection and comparison
      of the results of various methods of treatment.

PMID- 8884292
TI  - Sequential changes of bile contents in patients with obstructive jaundice from
      different etiologies.
AB  - BACKGROUND/AIMS: The decreasing of serum concentration of bilirubin and the
      ability of hepatocytes to excrete various biliary contents after release of
      obstructive jaundice are good indicators of recovery of liver function. We
      conducted this study to clarify whether different causes of obstructive jaundice
      have different effects on the biliary excretion and how they are different when
      obstruction is released. PATIENTS AND METHODS: Fifteen patients with obstructive
      jaundice undergoing percutaneous transhepatic catheter drainage or endoscopic
      nasobiliary drainage were classified into two groups, depending on the cause of
      obstruction: common bile duct stones (n = 7) and biliary tract tumors (n = 8).
      All patients in the gallstone group presented with acute cholangitis while only
      three patients in the tumor group had a positive bacteria culture in bile.
      Fasting biles were collected on the day of catheter placement and the 2nd, 4th,
      6th, 8th, 10th day thereafter. The sequential changes of biliary concentration of
      bilirubin, phospholipid, cholesterol, bile salts and serum bilirubin were checked
      and compared between the two groups. RESULTS: The difference in the improvement
      of jaundice between the stone and tumor group (p > 0.05) were not significant,
      nor were the excretion of biliary contents after relief of obstruction. The
      reduction of serum bilirubin paralleled with the increased excretion of biliary
      bile salts and bilirubin (gamma = -0.51, p < 0.01 and gamma = -0.4, p < 0.05) in
      tumor group, but not in the stone group. CONCLUSIONS: The decrease of serum
      bilirubin and the sequential changes of bile contents after relief of obstruction
      are quite similar in stone and tumor induced obstructive jaundice.

PMID- 8884293
TI  - Counts of bacteria and pyocites of choledochal bile in controls and in patients
      with gallstones or common bile duct stones with or without acute cholangitis.
AB  - BACKGROUND/AIMS: The number of colonies of bacteria and the number of pyocites
      present per ml of choledochal bile was studied. PATIENTS AND METHODS: There were
      42 controls, 100 patients with symptomatic gallstones, 42 patients with common
      duct stones without cholangitis and 24 patients with common duct stones and acute
      cholangitis. RESULTS: Control subjects had no bacteria present at gallbladder
      bile. Only 3% of patients with gallstones had more than 10(5) colonies per ml
      which increased to 36% in patients with common duct stones without cholangitis
      and to 84% among patients with acute cholangitis (p < 0.001). There were more
      polybacterial flora among patients with acute cholangitis and anaerobic bacteria
      were not seen in patients with gallstones. Patients with acute cholangitis had
      significantly more pyocites present at choledochal bile. CONCLUSION: There is a
      direct correlation between the number of colonies present per ml of choledochal
      bile and the severity of biliary tract disease. Patients with acute cholangitis
      had significantly more pyocites present at choledochal bile compared to
      gallstones or patients with CBD stones without cholangitis.

PMID- 8884294
TI  - No evidence for abnormal gallbladder emptying in Crohn's disease.
AB  - BACKGROUND/AIMS: An increased risk of gallstone development has been found in
      patients with Crohn's disease. This has been suggested to be due to abnormal bile
      acid metabolism. We investigated the possibility that Crohn's disease might alter
      gallbladder mechanical function and predispose to gallstone formation by
      incomplete emptying or prolonged contraction time of the gallbladder. MATERIALS
      AND METHODS: Seventeen patients with Crohn's disease (CD) and 20 healthy controls
      (CO) of similar age and sex (CD: 7 males, 31 +/- 13 years; 10 females, 30 +/- 9;
      CO: 10 males, 26 +/- 12; 10 females, 26 +/- 9) were compared. None of the
      patients or controls had gallstones. Using ultrasonography with computed volume
      calculation, the gallbladder was assessed in fasting state and every 10 min for
      70 minutes after ingestion of a standard fatty meal. RESULTS: Neither maximum
      volume (CD: 22 +/- 9 ml, CO: 25 +/- 15), residual volume after stimulation (CD: 3
      +/- 2 ml, CO: 6 +/- 6 ml), volume decrease in % (CD: 83 +/- 5%, CO: 78 +/- 9%),
      nor rate constants of emptying (CD: = 0.034/min, CO: = 0.033/min) were different
      between patients and controls. CONCLUSION: Abnormal gallbladder contractility
      does not seem to be a major cause of an increased risk of gallstone formation in
      Crohn's disease.

PMID- 8884295
TI  - Intestinal splinting for uncomplicated early postoperative small bowel
      obstruction: is it worthwhile?
AB  - BACKGROUND: Established indications (obstructing extensive fibrous adhesions) and
      contraindications (solitary band- and short segment midgut adhesive obstruction,
      purulence) of intestinal tube splinting have emerged from clinical practice. The
      benefit of tube splinting for early postoperative small bowel obstruction (SBO),
      however, is still a matter of debate. METHODS: From Jan 1980 until Dec. 1989, all
      patients undergoing relaparotomy for uncomplicated early postoperative SBO were
      randomized for enterolysis, gut decompression and repair (group A, 28 patients)
      or the same procedure plus tube splinting (group B, 28 patients). The patients
      were comparable with respect to gender, age and type of preceding operations;
      they were followed for 5-14 years or until death. RESULTS: In the early
      postoperative period, 3 incidences of reobstruction and 8 of other complications
      were observed in group A vs. 0 and 2, respectively, in group B. No patient died.
      During follow-up, one patient suffered late SBO, 2 patients recurrent partial SBO
      and one patient died of bowel perforation in group A vs two incidences of late
      SBO in group B. CONCLUSIONS: Intestinal splinting performed for early
      postoperative SBO rendered a significant reduction of early postoperative
      complications; the protective efficacy against early reobstruction was clinically
      apparent but reached borderline significance only. In respect to late intestinal
      complications, splinting was not superior to simple enterolysis. Early and late
      complications taken together and intestinal complications considered separately
      were significantly more frequent in patients without splinting.

PMID- 8884296
TI  - Primary repairing in penetrating colon injuries.
AB  - BACKGROUND/AIMS: The large bowel is injured in about 10% of penetrated abdominal
      injuries. Primary repair with colostomy has been discussed recently. MATERIALS
      AND METHODS: Between 1987 and 1995, sixty-five patients were operated on with
      penetrated colon injuries were treated with primary repair without colostomy. Any
      patient with one or more of the following criteria was excluded: Age > 60 years,
      blood pressure < 80/60 mmHg, time from injury to treatment > 8 hours, Penetrating
      abdominal trauma index > 50. RESULTS: The mean age of the patients was 31 and
      female/male ratio was 1/7. Fifty-one patients (78.5%) were exposed to colon
      injury by stabbing and 14 patients (21.5%) by gunshot. The most frequently
      injured segment was the transverse colon (36.9%). The liver was the most commonly
      injured organ associated with colon injury (32.3%). Colon wounds of 48 patients
      (73.8%) were treated with simple repair consisting of meticulous debridement. All
      gunshot wounds (14 patients) and 3 of the stab wounds were treated with
      segmentary resection and two layered anastomosis because of the massive colonic
      wall injury and/or impairment of the blood supply. The most common postoperative
      complication was wound infection (12.3%). Intraabdominal infection and leakage of
      the anastomosis were not observed. CONCLUSION: Primary repair or, if necessary,
      segmentary resection and anastomosis will be more appropriate in civilian colon
      injuries.

PMID- 8884297
TI  - Circular stapling techniques for low anterior resection of rectal carcinoma.
AB  - BACKGROUND/AIMS: This report provides our experience in 103 patients with
      adenocarcinoma of the rectum along with a general overview of the use of circular
      stapler in rectal surgery. MATERIALS AND METHODS: Forty-two patients were
      randomized to a rectal anastomosis using either the single (SST) or double
      stapling technique (DST). RESULTS: From February 1991 to the present, 61
      consecutive patients were treated to a rectal anastomosis using the DST.
      Perioperative mortality was 4.7 percent unrelated to the use of staplers.
      Statistically significant differences were noted: the mean distal resection
      margin measured 25.3 mm for SST and 35.0 mm for DST (p = 0.0274), without
      doughnut rings. Anastomotic stricture occurred in 3 patients (25%) using the 28
      mm cartridge and in 1 (1.4%) using the 31-mm cartridge, respectively (p =
      0.0082). To evaluate the different stapling techniques with bacterial
      contamination, the drain fluid was examined for lysozyme activity. When the SST
      was used, statistically significant enzyme activity increased as compared with
      the DST. Clinical leaks were noted in 9.5 percent (2/21) of the SST and in 2.4
      percent (2/82) of the DST. The median follow-up of patients in the randomized
      study was 45 months (range, 32-62 months). Of the patients who underwent a
      potentially curative resection, seven (17.9 percent) developed a local
      recurrence, with no statistically significant differences in the stapling
      techniques of local recurrence and overall survival. CONCLUSIONS: Our experience,
      and that reported in literature, suggests that the double stapling technique is
      useful for restorative resection of rectal cancers.

PMID- 8884298
TI  - Transcolonic approach for a stapled end-to-end colorectal anastomosis in low
      anterior resection.
AB  - We designed the transcolonic approach for a stapled end-to-end colorectal
      anastomosis using a premium curved EEA in low anterior resection. The advantage
      of this repair is the elimination of transanal introduction of the stapler by a
      second assistant from below, which make the stapled anastomosis technically
      easier and safer. The fact that the anvil can be removed from the center shaft by
      pressing on the anvil release button allows the anvil to be released from anus,
      which theoretically prevents suture break down. This procedure can be considered
      for selected patients who have anal structure and where it is impossible to
      insert the instrument.

PMID- 8884299
TI  - Segmental resection of the duodenum including the papilla of Vater for focal
      cancer in adenoma.
AB  - BACKGROUND/AIM: Adenoma of the papilla of Vater is a premalignant lesion
      frequently associated with focal cancer. This adenoma has been treated by a
      variety of methods, and a consensus for its standard treatment has not been
      reached. A method of resection which is safe and reliable is desired. METHOD: The
      distal part of duodenum and pancreas were separated. The pancreatic and bile
      ducts were exposed outside the pancreas and duodenum, respectively, and
      transected. Segmental resection of the distal part of the duodenum including the
      papilla of Vater was performed. The jejunum was elevated and anastomosed with the
      duodenum, bile duct, and pancreatic duct. RESULTS: The resection was safely
      performed on two patients with focal cancer in adenoma. Delayed gastric emptying
      which continued for 2 to 3 weeks, occurred in both patients. Postoperatively, the
      patients resumed a normal life and weigh the same as before surgery. CONCLUSION:
      Segmental resection of the duodenum including the papilla of Vater is a safe and
      effective treatment method for adenoma of the papilla of Vater, a premalignant
      neoplasm that is frequently associated with cancer.

PMID- 8884300
TI  - Major acute inflammatory complications of diverticular disease of the colon:
      planning of surgical management.
AB  - BACKGROUND/AIMS: The aim of this study was to determine the most appropriate
      surgical strategy in the management of patients with major inflammatory
      complications of colonic diverticular disease. MATERIALS AND METHODS: Out of 259
      patients affected by complicated diverticular disease of the colon, 43
      consecutive patients (16.6%) who underwent urgent or emergency surgical
      intervention for diverticular perforation during a 20-year period (1975-1994)
      were retrospectively analyzed. According to the changes in the surgical approach
      over the time, the series was divided into two groups: 1975-1985 group A (n =
      23), 1986-1994 group B (n = 20). The clinical diagnosis was confirmed by
      operative and pathologic findings. RESULTS: Out of 43 patients, 11 underwent
      derivative procedure and 32 resection. There were no significant differences
      among the two groups of patients according to sex ratio and mean age. The overall
      percentage of patients in group B who underwent resective procedure (100%) was
      significantly greater in comparison with that in group A (52%) (p < 0.001).
      Colostomy and drainage was employed only during the first period (30%)(vs group
      B, p < 0.05) and the proportion of patients who underwent primary resection and
      anastomosis was significantly higher during the second period (45%) (vs group A,
      p < 0.05). CONCLUSIONS: It must be stressed that resection of the diseased
      segment at initial operation appears mandatory; one-stage procedure is indicated
      when infection is confined to the mesentery, while resection and anastomosis with
      covering colostomy (two-stage procedure) is preferable whenever peritoneal
      contamination has occurred. Hartmann's operation remains the procedure of choice
      in the patients presenting known impaired immunity or fecal contamination.

PMID- 8884301
TI  - Surgical results of corrosive injuries involving esophagus to jejunum.
AB  - BACKGROUND/AIM: Severe corrosive injury involving esophagus to jejunum remains an
      unique surgical problem which is associated with high mortality and morbidity.
      MATERIAL AND METHODS: Herein we report the outcomes of 28 caustic patients who
      underwent resections of the stomach, duodenum, a segment of jejunum, and adjacent
      involving organs. RESULTS: In all of these patients except one, esophagectomy was
      also performed. The concomitant procedures included pancreaticojejunostomy (n =
      24), choledochojejunosotmy (n = 4), cholecystostomy (n = 4), common bile duct or
      pancreatic duct drainage, feeding and drainage jejunostomies, and cervical
      esophagostomy. Major complications consisted of bile leakage (n = 10), bile
      bronchial fistula (n = 2), internal bleeding due to vessel necrosis (n = 5),
      peritonitis (n = 4), acute renal failure (n = 4), and septicemia (n = 4). There
      were 13 hospital deaths (46.4%) and three late deaths. Eight out of 12 survivors
      underwent subsequent reconstruction of esophagus. The remaining four survivors
      depended on jejunostomy feeding. CONCLUSIONS: Early approaches and appropriate
      procedures can save a number of patients with corrosive injury involving
      esophagus to jejunum.

PMID- 8884302
TI  - Significance of a modified decompression method in enhancing the safety of
      esophagus operations.
AB  - BACKGROUND/AIMS: Every esophageal surgeon employees methods to reduce the risk of
      infection caused by the pool of debris and organisms proximal to a destructive
      esophageal lesion and to prevent distension of the viscera adjacent to the suture
      line of the anastomosis. MATERIAL AND METHODS: The authors report on a retrograde
      drainage which was devised to prevent the distension of the loop adjacent to
      anastomosis following esophagectomy. RESULTS: This modified decompression method
      and simultaneous enteral feeding decreased the frequency of postoperative
      pulmonary complications significantly (1973-90 complication rate: 16.5% - 119/722
      vs. 1990-95 complication rate: 7.7% - 17/221). CONCLUSION: The retrograde
      drainage facilitates safe and effective decompression even in the recumbent
      position, doesn't inconvenience the patient, promotes early mobilization and can
      be maintained till complete recovery of the anastomosis.

PMID- 8884303
TI  - Precancerous gastric lesions and Helicobacter pylori.
AB  - BACKGROUND/AIMS: Previous publications in the literature have reported an
      association between incidence of Helicobacter pylori (HP) infection and gastric
      cancer. The role of HP in precancerous gastric lesions or in their evolution
      towards neoplastic disease is not so clear. MATERIALS AND METHODS: We studied 174
      patients with atrophic gastritis. RESULTS: Intestinal metaplasia (IM) was
      detected in 165 subjects of the patients and different grades of dysplasia were
      observed in 32 subjects. HP was found in 75 (52.8%) of 165 subjects with IM, in 7
      (34.7%) with both IM and dysplasia and in 3 with dysplasia alone. There was no
      significant difference in the prevalence of HP infection in the three IM types,
      type I (47.7%), type II (54.7%) and type III (48.4%) (p = n.s.). In contrast, the
      prevalence of HP positive patients was significantly lower in dysplasia (10/32 vs
      22/32; p < 0.005). At the same time, the frequency of HP was significantly lower
      for subjects with IM and dysplasia than for those with type I IM (41/83 vs 7/32;
      p = 0.01). CONCLUSIONS: At present, in our experience, HP infection is rather
      infrequent in type III IM and it is found less often in cases of dysplasia. We
      have taken these results to suggest that the modified gastric mucosa becomes
      inhospitable for HP and, consequently, that other factor are probably responsible
      for promoting gastric carcinogenesis.

PMID- 8884304
TI  - One-week low-dose triple therapy vs. two-week medium-dose double therapy for
      H.pylori infection.
AB  - BACKGROUND/AIMS: Our study is to compare a short-term low-dose triple therapy
      with a long-term medium-dose double therapy for H.pylori eradication. MATERIALS
      AND METHODS: One hundred and ten consecutive patients, suffering from dyspeptic
      symptoms, with H.pylori infection, were randomly allocated to one of the
      following 2 groups with different therapeutic regimens: A) omeprazole 20 mg/day
      for 7 days, tinidazole 500 mg bid for 7 days, clarithromycin 250 mg bid for 7
      days (55 pts, 20 with peptic ulcer); B) omeprazole 20 mg bid for 14 days,
      amoxycillin 1000 mg bid for 14 days (55 pts, 28 with peptic ulcer). The "H.pylori
      status" was evaluated by means of histology, culture and urease test, at entry
      and 8 weeks after treatment. RESULTS: Two group A and one group B pts didn't
      complete the treatment. The H.pylori eradication was obtained in 38 pts of group
      A (71.69%) (C.I.95%: 55.19176-80.86293), in 31 of group B (58.49%) (C.I.95%:
      42.32777-69.7017); on Intention-to-Treat analysis, the rate of eradication gave
      similar results. Side effects occurred in 9 pts of group A (16.98%), in 8 of
      group B (14.81%). CONCLUSIONS: Short-term low-dose triple therapy with
      omeprazole/tinidazole/clarithromycin has a better cost/benefit ratio than long
      term dual therapy with omeprazole/amoxycillin in the H.pylori eradication, but it
      causes more side-effects.

PMID- 8884305
TI  - Omeprazole versus histamine H2 receptor antagonists in the treatment of acute
      upper non-variceal bleeding.
AB  - BACKGROUND/AIMS: To compare the efficacy of omeprazole, a proton pump inhibitor,
      with Histamine H2 receptors antagonists in the control and recurrence of non
      variceal upper gastrointestinal bleeding. PATIENTS AND METHODS: Seventy-one
      patients (Group A, Omeprazole) with definite diagnosis of upper gastrointestinal
      bleeding of non-variceal origin during January 1993-Dec.1994, compared
      retrospectively with 119 patients (Group B, Ranitidine) with similar criteria
      during 1987-1993. Patients in both groups were matched as compared to sex, age
      and risk factors. Active treatment was omeprazole 40 mg B.D (twice daily) and
      then orally in group A compared with ranitidine intravenously 50mg TDS (three
      times daily) and then 150 mg B.D orally in group B. All patients in both groups
      had endoscopy at the time of presentation or within 24 hours. Endoscopic
      treatment was applied in some of the patients to arrest acute bleeding. The
      efficacy of treatment was gauged by the number of blood transfusions needed to
      maintain Hb., evidence of re-bleeding and need for surgery. RESULTS: The patients
      were well matched for endoscopic diagnosis except duodenal ulcers, which were
      more common in group A (P < 0.05). In group A out of 71 patients, 5 had
      rebleeding and 2 required surgery. In group B, out of 119 patients 12 rebled and
      10 required surgery. Statistically there was no difference between groups (p =
      0.52 by using Kendall's Tau B). Nine patients in omeprazole group received 2
      units blood transfusion, 6 patients > 4 units and 3 patients > 6 units, while in
      the H2 blocker group, 16 patients received 2 units, 15 patients received > 4
      units, and 3 patients > 6 units of blood transfusion. Statistically there was no
      difference between groups with regard to number of transfusions, rebleed or the
      need for surgery. CONCLUSIONS: In our study we found no difference between
      omeprazole and histamine H2 receptors antagonists in controlling and recurrence
      of upper gastrointestinal bleeding.

PMID- 8884306
TI  - Evaluation of gastric ulcer healing with mucosal microvascular architecture.
AB  - BACKGROUND/AIMS: There is presently no consensus on how long treatment of gastric
      ulcers should be continued to prevent ulcer recurrence. Therefore, we
      investigated the histologic state of healing, and the recurrence of gastric
      ulcers with Helicobacter pylori infection classified by gastric mucosal
      microvascular architecture as completely and incompletely healed. MATERIAL AND
      METHODS: We obtained biopsy specimens from healed gastric ulcers in 71 patients
      who had been treated for eight weeks with omeprazole. The gastric mucosal
      microvascular architecture of the biopsy specimens was observed by the alkaline
      phosphatase staining method. RESULTS: We found a significant correlation between
      the mucosal microvascular architecture in the biopsy specimens and the histologic
      state of ulcer healing Recurrences were significantly more frequent in ulcers
      classified by microvascular architecture as incompletely healed than in
      completely healed ulcers. CONCLUSION: Observing the microvascular architecture of
      healed gastric ulcers is very useful for judging the state of healing, and
      therapy should be continued until ulcers are classified by this method as
      completely healed.

PMID- 8884307
TI  - Hepatitis C and the controversies it creates relative to liver transplantation
      and autoimmune hepatitis.
AB  - The paradox of hepatitis C. An agent that persists in tissue for years by
      escaping the immune system and not killing but only damaging its host while
      simultaneously being associated with autoimmune hepatitis as well as other
      putative autoimmune diseases is presented. Liver transplantation necessitates
      immune suppression and is associated with progressive HCV disease albeit at a
      rather slow rate. Diagnosis and treatment concerns are raised and discussed.

PMID- 8884308
TI  - Effects of low molecular weight glycoproteins in chronic hepatitis B.
AB  - BACKGROUND/AIMS: We evaluated the effect of low molecular weight glycoproteins
      isolated from animal spleen (Polyerga) in ten patients with biopsy proven chronic
      HBV infection with ongoing replication. MATERIAL AND METHODS: Polyerga was given
      intramuscularly trice weekly and orally 3 tablets daily for 24 weeks. The effect
      on viral replication was evaluated by measuring HBV-DNA and HBeAg in serum.
      RESULTS: In three out of ten, HDV-DNA became undetectable and ALT decreased (mean
      pre-treatment ALT 87.2 +/- 55.38SD, mean post-treatment ALT 62.6 +/- 41.86SD p =
      0.026 t-test and Wilcoxon test p = 0.014). During the first month of Polyerga
      application transient increase of serum ALT was observed in 50%. In HBeAg
      negative patients and in patients with low pre-treatment level of HBV-DNA (below
      250pg/ml) there was significant decrease of ALT by t-test (p = 0.022), Wilcoxon
      (p = 0.028) and Sign test (p = 0.041) in contrast to those with HBV-DNA above
      250pg/ml. CONCLUSION: The effect of increasing the cytolysis shows that these
      drugs are active, probably by increasing the lymphokine secretion and the
      generation of cytotoxic T-cells. The absence of side effects, its ability to
      reduce viral replication and lower ALT activity even in patients with liver
      cirrhosis warrants further studies as a "second drug" or as a drug of choice when
      IFN is contraindicated.

PMID- 8884310
TI  - Liver transplantation--perspective from Hong Kong.
AB  - BACKGROUND/AIMS: We report our experience of 27 orthotopic liver transplantations
      in 26 patients performed at Queen Mary Hospital, Hong Kong during the period of
      October 1991 to October 1995. PATIENTS AND METHODS: There were 19 adults and 7
      pediatric patients with a mean age of 29 years (range 8 months to 62 years). The
      underlying liver diseases of the 26 patients were biliary atresia (n = 6),
      Alagille syndrome (n = 1), primary biliary cirrhosis (n = 2) cryptogenic
      cirrhosis (n = 2), alcoholic cirrhosis (n = 5), Wilson's disease (n = 1),
      fulminant hepatic failure (n = 3), polycystic liver (n = 2), secondary biliary
      cirrhosis (n = 1), HBV cirrhosis (n = 2) and autoimmune hepatitis with
      hepatocellular carcinoma (n = 1). The pathology leading to re-transplantation in
      a pediatric patient was post-transplant hepatitis of unknown etiology. The liver
      grafts were obtained from 19 brainstem dead and 8 living donors. The pediatric
      patient requiring re-transplantation received a left lateral segment graft from
      her mother. Two adults received left lobe grafts from their family members.
      RESULTS: The overall graft survival is 88% and patient survival is 92%. There
      were only 2 deaths: one patient developed primary graft nonfunction and died from
      intracerebral bleeding 39 days after transplantation and the other died from
      graft rejection resistant to salvage by steroid pulse and OKT3. The other
      patients are well with functioning grafts. CONCLUSIONS: We hope that the current
      success rate can convince people in our locality in cadaveric organ donation so
      that living donors do not run the risk of dying from the operation, although the
      risk is estimated to be very small.

PMID- 8884309
TI  - Effects of canrenoate potassium, an aldosterone antagonist on portal hemodynamics
      in patients with compensated liver cirrhosis.
AB  - BACKGROUND/AIMS: Long-term administration of spironolactone is reported to reduce
      portal pressure in cirrhotic patients. We examined the effects of acute
      administration of canrenoate potassium, an aldosterone antagonist, on portal
      hemodynamics in compensated cirrhotic patients using noninvasive duplex Doppler
      ultrasonography. MATERIALS AND METHODS: Baseline values were obtained in the
      fasting state, and then 200mg of canrenoate potassium in 10ml of saline solution
      was intravenously administered to 22 patients, whereas 10ml of saline solution
      was administered as a placebo to 8 patients. RESULTS: The portal cross-sectional
      area, portal blood velocity and portal blood flow decreased by 5.3 +/- 9.2, 10.4
      +/- 8.7% and 13.0 +/- 12.4%, respectively at the nadir 60min after administration
      and these decreases persisted until 120min. Placebo did not affect these
      parameters of portal hemodynamics. Eleven responders, who had a more than 10%
      drop in portal blood flow 60min after administration, had significantly higher
      levels of plasma aldosterone than 8 non responders who had less than 10% drop.
      The reduction rate of portal blood flow was closely correlated with plasma
      aldosterone level. CONCLUSIONS: These findings suggest that aldosterone
      antagonist directly causes a reduction in portal blood flow, probably through
      inhibition of aldosterone-induced vasoconstrictive action.

PMID- 8884312
TI  - Primary biliary cirrhosis (PBC) in an European country--a description of death
      rates in The Netherlands (1979-1992).
AB  - BACKGROUND/AIMS: In 1979, separate liver transplantation (LT) and primary biliary
      cirrhosis (PBC) death rate registration became available in The Netherlands (15
      million inhabitants). The objective of this study was to investigate death rates
      from 1979-1992 and analyse the impact of LT. PATIENTS AND METHODS: PBC was either
      a primary or secondary cause of death. Rates were expressed as absolute numbers
      or per million inhabitants in the corresponding age category. Age classes of 5
      years were used. The Netherlands was divided in four regions, North, South, East
      and West. Standardized mortality ratios (SMR) were used for calculation of
      regional differences. RESULTS: In the 14 year period between 1979-1992, 417
      persons died from and 179 persons died with PBC, totaling 596 PBC patients (6.3
      per million inhabitants > or = 35 years). No person younger than 35 died. Eighty
      two percent were female, with a corresponding female/male ratio of 4.2 per
      million females/males inhabitants. In region South there were significantly fewer
      deaths (SMR 66%, p < 0.001) and in region North significantly more (SMR 141%, p <
      0.05). The median age class at death was 70-74 (males and females alike). At age
      35-59, death from PBC in 1992 per million was 1.2, and for > or = 65 years 15.7.
      In age class 80-84, the highest death rate from or with PBC was found with 28
      deaths per million inhabitants and with a female/male ratio of 3.6. In 1992, with
      two deaths only, LT appeared to have nearly eliminated death from PBC in the age
      category 35-59 years. CONCLUSION: Death from PBC mainly occurs in the old and
      very old, who may never seek a specialized center. This indicates a more specific
      management and therapy for this particular group is needed.

PMID- 8884311
TI  - Oxidative damage in the liver induced by ischemia-reperfusion: protection by
      melatonin.
AB  - BACKGROUND/AIMS: The protective effect of mela tonin against the damage inflicted
      by reactive oxygen species during liver ischemia-reperfusion was investigated in
      male Sprague-Dawley rats using both biochemical and morphological parameters.
      MATERIALS AND METHODS: For biochemical analyses the levels of lipid peroxidation
      products [malonaldehyde (MDA) + 4-hydroxyalkenals (4-HDA)], levels of reduced
      glutathione (GSH) and oxidized glutathione (GSSG), and the activities of GSH
      peroxidase (GSH-Px), GSH reductase (GSSG-Rd) and glucose-6-phosphatase (G6Pase)
      were estimated. Also the number of polymorphonuclear neutrophils (PMNs) in
      injured livers was counted in histological sections. RESULTS: After 40 min of
      ischemia followed by 60 min of reperfusion the hepatic levels of MDA + 4-HDA
      increased. Pretreatment of the animals with melatonin abolished the rise in MDA +
      4-HDA induced by ischemia-reperfusion. GSH concentrations decreased and GSSG
      increased during ischemia-reperfusion and, again melatonin counteracted these
      changes. Additionally, the activities of two antioxidative enzymes (GSH-Px and
      GSSG-Rd) decreased during the experimental period with melatonin preventing the
      change in GSSG-Rd. G6Pase activity was not influenced by either ischemia
      reperfusion or by melatonin administration. Morphologically, PMN infiltration was
      obvious in the ischemia-reperfusion damaged liver, a change also partially
      reversed by melatonin. CONCLUSIONS: In this model of liver ischemia-reperfusion
      injury, exogenously administered melatonin effectively protected against
      oxidative damage. The hepatic parameters which illustrated this protection were
      reduced lipid peroxidation products, lowered PMN infiltration, increased GSH and
      reduced GSSG levels, and elevated GSSG-Rd activity all of which were observed in
      melatonin-treated rats in which damage due to ischemia-reperfusion had been
      induced.

PMID- 8884313
TI  - Influence of endotoxemia on hepatic energy metabolism in rats with obstructive
      jaundice.
AB  - BACKGROUND/AIMS: A secondary insult in patients with obstructive jaundice can
      lead to multiple system organ failure. We evaluated the influence of endotoxin on
      hepatic energy metabolism and hepatic tissue blood flow in obstructive jaundiced
      rats. MATERIAL AND METHODS: Male Sprague-Dawley rats were divided into a control
      group, an endotoxin administration group, an obstructive jaundice group, and an
      obstructive jaundice with endotoxin administration group. To evaluate hepatic
      energy metabolism, we have measured arterial blood ketone body ratio, and
      arterial blood total ketone body concentration. Hepatic tissue blood flow was
      determined by laser Doppler velocimetry. RESULTS: In the endotoxin administration
      group, no change was observed in hepatic energy metabolism. However, the
      obstructive jaundice group was associated with decreased hepatic tissue blood
      flow shortly after the outset of jaundice, while no change was observed in
      hepatic energy metabolism until 3 weeks later. In the obstructive jaundice with
      endotoxin administration, a significant decrease in hepatic tissue blood flow and
      an increase in hepatic energy metabolism were measured. CONCLUSION: Endotoxin
      administration alone had no influence on hepatic energy metabolism, while
      endotoxin administration in the presence of obstructive jaundice results in a
      rapid decrease in hepatic energy metabolism. This occurred as a result of the
      secondary insult of endotoxin in the setting of decreased hepatic tissue blood
      flow caused by obstructive jaundice.

PMID- 8884314
TI  - The prognosis of patients with hepatocellular carcinoma of multicentric origin.
AB  - BACKGROUND/AIMS: The characteristics of patients with multicentric hepatocellular
      carcinoma (HCC) differ from those of patients with intrahepatic metastatic HCC.
      However, there are few reports regarding the long-term results in patients with
      HCC of multicentric occurrence. The purpose of this study was to clarify the
      prognosis of a group of patients with multicentric HCCs. MATERIALS AND METHODS:
      We evaluated the outcome in 28 patients with multiple hepatocellular carcinoma
      (HCC) suggestive of multicentric occurrence, all of whom underwent hepatic
      resection. The disease-free survival, recurrence pattern and survival were
      analyzed in the two subgroups of 12 patients with single advanced HCC (AdHCC)
      nodule and an early HCC (eHCC) or early advanced HCC (eAdHCC) nodule [Group A]
      and 16 patients with two AdHCC lesions [Group B]. These data were also compared
      with those of 58 patients with solitary AdHCC [Group C]. RESULTS: Both the
      disease-free survival and survival periods for Groups A and C were significantly
      longer than those for Group B, while no significant difference was seen between
      Group A and C. No significant differences among the three groups were recognized
      in the incidence of various types of recurrence pattern. CONCLUSIONS: The long
      term results in patients with multicentric HCC apparently vary depending on the
      pathological condition at the time of operation. Among patients with multicentric
      HCC, those with AdHCC combined with an eHCC or eAdHCC are likely to show improved
      prognosis as a result of hepatic resection.

PMID- 8884315
TI  - Clinicopathologic features of early hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: This study attempts to clarify the clinicopathologic definition
      of early hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: We evaluated 57
      patients, with HCCs less than 3 cm in diameter, in terms of prognosis, incidence
      of extrahepatic metastasis, and tumor recurrence rate following treatment.
      RESULTS: Survival was related to both tumor number and histologic
      differentiation, but was not related to tumor size. Furthermore, prognosis
      appeared to depend on the functional reserve of the liver. The incidence of
      extrahepatic metastasis was related to histologic differentiation. There was no
      significant difference in the recurrence rates of patients with uninodular tumors
      in terms of tumor size. CONCLUSIONS: Our findings indicate that early HCCs
      measure 15 mm or less in diameter, are uninodular, and are histologically well
      differentiated. Finally, the functional reserve of the liver will likely be an
      additional parameter that will further characterize early HCCs.

PMID- 8884316
TI  - Indications for, and effectiveness of, a second hepatic resection for recurrent
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Second hepatic resection (SHR) for recurrent hepatocellular
      carcinoma (HCC) appears to have a better prognosis than other treatments;
      however, it is not clear whether this is the result of the procedure, or of the
      underlying condition of patients undergoing this treatment. MATERIALS AND
      METHODS: Consecutive hepatic resection for 13 years, many patients suffered from
      recurrence in the remnant liver. After detection of recurrence, these lesions
      were treated in various ways including SHR. In this communication, recurrent
      patients were divided into SHR patients and non-SHR patients. In these two
      groups, we analyzed clinicopathologically. RESULTS: After 341 curative hepatic
      resections for HCC, recurrences presented in 193 patients (57%). SHR was
      performed in 31 patients (16%), while the other 162 patients (84%) underwent
      other treatments. At first resection, the group did not significantly differ in
      sex, age, evidence of hepatitis infection, liver function tests, tumor size,
      presence of portal vein invasion and evidence of histologic cirrhosis. SHR
      patients had more tumor-free days following first resection than non-SHR patients
      (p < 0.05). The survival rate following recurrence for SHR patients was better
      than that of non-SHR patients (p < 0.05). Among the non-SHR patients, 23 patients
      met criteria for the procedure. Survival rate for the 31 SHR patients also was
      better than that of these 23 patients (p < 0.05). CONCLUSION: Since SHR is safe,
      effective, and offers an improved prognosis for recurrent HCC, it should be the
      treatment of choice whenever possible.

PMID- 8884317
TI  - Predictive factors for recurrence after percutaneous ethanol injection for
      solitary hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Intrahepatic recurrence frequently occurs in patients with
      hepatocellular carcinoma (HCC) even after successful percutaneous ethanol
      injection (PEI). This study investigated factors predicting recurrence after PEI
      for solitary HCC. MATERIALS AND METHODS: The subjects were 31 patients with
      solitary HCC (10-29 mm) who received successful PEI. We investigated the
      relationship of pretreatment clinicopathological variables to recurrence-free
      survival including: age, gender, alcohol abuse, tumor size, tumor staining, tumor
      differentiation, serum alpha-fetoprotein (AFP) level, associated liver disease,
      and Child-Pugh classification. Differences in recurrence-free survival among
      subgroups classified by each factor were evaluated using log-rank tests. RESULTS:
      Median recurrence-free survival time, 1 and 2 years recurrence-free survival
      rates of all 31 patients were 1.57 years, 72.2% and 45.4%, respectively. Among
      the 9 variables evaluated, serum AFP level of 20 ng/ml or less (p < 0.005) and
      absence of cirrhosis (p = 0.025) were factors favoring longer recurrence-free
      survival significantly. CONCLUSION: These results indicate that HCC patients with
      higher serum AFP level or coexistent cirrhosis should be followed more closely
      even after successful PEI.

PMID- 8884318
TI  - Endoscopic stenting in obstructive jaundice due to liver metastases: does it have
      a benefit for the patient?
AB  - BACKGROUND/AIMS: The goal of this report is to describe our experience with the
      palliative endoscopic treatment of jaundice occurring in the setting of liver and
      hilar metastases of a distant primary malignancy. MATERIAL AND METHODS: We
      retrospectively analyzed the clinical course of 29 consecutive patients with
      metastatic tumors not originating in the hepatobiliopancreatic area, who were
      treated by endoscopic retrograde cholangiopancreatography with endoprostheses
      insertion. RESULTS: We achieved a complete follow-up in 24 out of the 29 patients
      (11 women, median age 69 years). The primary tumor site was the colorectum in 15
      patients, stomach in 4, lung in 2, breast and prostate in 1 and one patient had a
      lymphoma. The median bilirubinemia before therapy was 16 (1.8-31) mg/dl and the
      median minimum serum bilirubin reached after stenting was 2.6 (0.3-11.5) mg/dl.
      Stent dysfunction was observed in 33.5% of the patients and stent change was
      necessary 13 times. The median survival after therapy was 4 (2.5-19) months for
      patients with colon tumors and 3 (0.5-12) months in patients with other cancers.
      An improvement in the quality of life was obtained in 75% of the patients after
      endoscopic treatment. CONCLUSIONS: Endoscopic stenting should be attempted even
      on patients with obstructive jaundice due to liver metastases.

PMID- 8884319
TI  - The serum levels of soluble interleukin-2 receptor levels in patients with
      obstructive jaundice.
AB  - BACKGROUND/AIMS: Increased susceptibility to infection in patients with
      obstructive jaundice is well recognized. Depression of reticuloendothlial system
      phagocytic function and suppression of cellular immunity suggested by in vivo
      studies have been postulated as the cause. It has been shown that increased serum
      soluble interleukin-2 receptor (sIL-2R) levels are the marker of immune system
      activation, especially T cell activation. The purpose of this study was to
      evaluate cellular immune system activation by measuring serum sIL-2R levels in 18
      patients with obstructive jaundice (11 with choledocholithiasis, 7 with malignant
      obstructive jaundice), 10 patients with liver cirrhosis and 10 healthy subjects.
      MATERIAL AND METHODS: Serum sIL-2R levels were measured by using ELISA
      (Boehringer Manheim). Lymphocyte subgroups were determined by flowcytometry.
      Serum immungolubulins (IgG, IgA, IgM) and autoantibodies such as antinuclear
      antibody, rheumatoid factor, anti-thyroglobulin and anti-microsomal antibody were
      measured. RESULTS: The levels of serum sIL-2R were found to be 47.1-121.2 (mean
      77.3, SD +/- 20.1) pmol/l in healthy subjects, 82.8-199.2 (mean 150.9 +/- 32.2)
      pmol/L in patients with liver cirrhosis and 32.6-172.5 (mean 121.7 +/- 40.6)
      pmol/L in patients with obstructive jaundice. Serum sIL-2R levels were
      significantly higher in patients with liver cirrhosis or obstructive jaundice
      than in healthy subjects (p < 0.01 and p < 0.05 respectively). There is a
      significant difference in levels between patients with choledocholithiasis and
      with malignant obstructive jaundice (p < 0.01). Serum sIL-2R levels were measured
      higher in patients with liver cirrhosis than those in patients with obstructive
      jaundice (p < 0.059). CONCLUSIONS: In patients with obstructive jaundice, and to
      a lesser extent in those with liver cirrhosis, in vivo activation of immune
      system may be considered possible.

PMID- 8884320
TI  - Cavernous transformation of the portal vein is associated with pancreatic duct
      atrophy.
AB  - BACKGROUND/AIMS: To determine whether or not portal venous obstruction affects
      pancreatic duct size. MATERIAL AND METHODS: The ERCP findings of 43 of 51
      subjects with cavernous transformation of the portal vein (CTPV) were studied
      prospectively. In three, the ERCP failed to demonstrate the pancreatic duct (PD)
      for technical reasons and in 8 of the original 51 subjects, the ERCP was not
      attempted because of a lack of indications and unwillingness of the subject to
      undergo the procedure. The ERCP findings of the remaining 40 subjects were
      compared with those of 23 normal concurrent controls and those of reference
      controls. RESULTS: In 21 of the 51 patients, an underlying disorder responsible
      for portal vein thrombosis and cavernous transformation was identified. Despite a
      full clinical, radiologic, hematologic and biochemical evaluation, no etiology
      for CTPV was found in the remaining 30 patients. The pancreatic duct diameter was
      measured at the widest portion of the duct where it traverses the head of the
      pancreas. In 34 of the 40 patients with CTPV and a successful ERCP, the
      pancreatic duct was smaller (less than 2.28 mm in diameter) than that of
      concurrent control subjects and a reference control group (p < 0.05). In only 6
      subjects with CTPV was the pancreatic duct size within normal limits. In 3 of
      these 6, a confounding common bile duct stone was shown to be present and may
      have accounted for the pancreatic duct enlargement as compared to the other 34
      subjects with CTPV. CONCLUSIONS: These results indicate that a smoothly narrowing
      pancreatic duct hypoplasia or atrophy can be demonstrated in 85% of cases with
      CTPV. It is speculated that this finding is a consequence of the obstructed
      pancreatic venous drainage that occurs with CTPV.

PMID- 8884321
TI  - Duodenal diverticulum at endoscopic retrograde cholangiopancreatography, analysis
      of 123 patients.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the frequency, clinical
      characteristics, findings and possible varieties of treatment of duodenal
      diverticula in Finnish patients diagnosed by endoscopic retrograde
      cholangiopancreatography. MATERIAL AND METHODS: Among 1735 patients investigated
      by endoscopic retrograde cholangiopancreatography, there were 123 patients with
      one or more duodenal diverticula and with sufficient clinical data available for
      this study. Mean age of the patients was 63 years. The male/female ratio was
      61/62. Three hundred twenty age and sex matched patients undergoing ERCP during
      the same time period, but without duodenal diverticula, served as controls.
      RESULTS: Sixty-one percent of the diverticula were juxtapapillary. Pain and
      jaundice were the symptoms indicating ERCP in 62% of patients. Laboratory
      findings were mostly within normal limits. A hepatic or pancreatic tumor was
      suspected in twelve patients at ultrasound and computer tomography, and five of
      them had cancer. In 65 patients, both ducts were cannulated at ERCP. In eleven
      patients, the finding was normal. There was no significant difference in the
      incidence of pathologic ERCP findings between the patients with juxtapapillary
      diverticula and diverticula in other parts of duodenum, except pancreatic duct,
      which was more frequently abnormal in patients with a non-juxtapapillary
      diverticulum. The patients with juxtapapillary diverticula had not had previous
      related complications or operations significantly more often than patients with
      diverticula in other parts of duodenum. The patients with juxtapapillary
      diverticula had significantly more often biliary stones at ERCP than control
      patients and they had idiopathic pancreatitis twice as often as control patients,
      but the difference was not statistically significant. In three patients, the
      therapy was directed to the diverticulum and 80 patients had some other
      treatment. CONCLUSION: These data do not reveal any clear correlation between a
      juxtapapillary diverticulum and pancreato-biliary disorders. However, common bile
      duct stones were more often found in patients with a juxtapapillary diverticulum
      than in controls.

PMID- 8884322
TI  - Cystic neoplasm mistaken for pancreatic pseudocyst.
AB  - The authors report a case of cystic neoplasm of the pancreas treated by
      cystojejunostomy two years and half earlier. On that occasion, a false diagnosis
      of pancreatic pseudocyst had been suggested. Cystic neoplasm of the pancreas has
      a far better prognosis than adenocarcinoma. However, early detection is difficult
      and erroneous initial diagnosis may lead to delayed treatment and poor long-term
      results. In our case, though surgical treatment was aggressive and apparently
      radical, early recurrence of neoplasm was observed. Only early accurate diagnosis
      of pancreatic cystadenocarcinoma might improve the results of surgical treatment.

PMID- 8884323
TI  - Reconstruction of alimentary continuity after subtotal duodenopancreatectomy.

PMID- 8884324
TI  - Hassab operation with intraoperative endoscopic injection sclerotherapy ("Hassab
      EIS") for esophagogastric varices: with an autopsied case after excessive gastric
      vascular damage.
AB  - BACKGROUND/AIMS: Endoscopic injection sclerotherapy (EIS) does not always treat
      advanced esophagogastric varices completely. Moreover, it may cause deterioration
      of gastric varices and may result in gastric hemorrhages. We would like to
      emphasize a combination treatment of the obliteration therapy of intramural
      varices by EIS and the transabdominal devascularization with splenectomy by
      Hassab's operation for such advanced esophagogastric varices. The purpose of this
      study is to develop an effective, less-painful procedure, having the fewest
      operational risks and a minimum number of treatment days. MATERIALS AND METHODS:
      We tried both therapies simultaneously (Hassab+EIS) on four patients with
      esophagogastric varices. RESULTS: Excessive vessel damage occurred in one patient
      which resulted in postoperative bleeding. He subsequently fell into sepsis/DIC
      and eventually died on the 9th POD. The three other patients are doing well and
      required less hospitalization time and a fewer number of additional EIS
      treatments than the esophageal transection group or the Hassab's operation group.
      CONCLUSION: From the reconsideration of the autopsied case, it is important to
      limit the distribution of the sclerosant only in the varicose veins of the lower
      esophagus and the upper stomach.

PMID- 8884325
TI  - Cytomegalovirus enteritis causing massive bleeding in a patient with AIDS.
AB  - An emergency operation was performed on a 58 year-old heterosexual male patient
      for massive lower gastrointestinal bleeding, which was caused by cytomegalovirus
      (CMV) related ulceration at the terminal ileum. Pre-operative endoscopic
      evaluation revealed multiple esophageal and gastric ulcerations in upper
      gastrointestinal tract and much fresh blood in distal colon. Angiography showed
      vascular tufts and extravasation of contrast medium in the cecal area.
      Angiodysplasia of cecum with massive bleeding was initially impressed. However,
      CMV enteritis was identified in the resected ileum, the diagnosis of Acquired
      Immunodeficiency Syndrome (AIDS) was confirmed by subsequent serological tests.
      AIDS was unknown to treating physicians until diagnosed by pathological specimen.
      Massive lower gastrointestinal bleeding related to CMV ulceration in small bowel
      is rare, we report this unusual presentation and highlight the the suspicion of
      immunocompromised state of patients with unusual, multiple gastro-intestinal
      ulcers.

PMID- 8884326
TI  - Cholestatic jaundice due to Ormond's disease (primary retroperitoneal fibrosis).
AB  - A case of a 51-year-old man, who presented with cholestatic jaundice due to
      common bile duct compression produced by primary retroperitoneal fibrosis, is
      reported. The patient was operated on two years earlier because of
      hydronephrosis, when the disease was diagnosed. Cholangiopancreatography revealed
      a "double duct sign", disclosing another benign cause for this radiographic sign,
      that once was considered to be pathognomonic of pancreas cancer. The bile duct
      stricture was managed by the insertion of an endoscopic endoprosthesis. This is
      the first report of jaundice due to Ormond's disease and the third, due to
      retroperitoneal fibrosis.

PMID- 8884327
TI  - Hepatoid adenocarcinoma of the stomach: a case report.
AB  - A patient with primary gastric carcinoma showing a high level of serum a
      fetoprotein (AFP) (368 ng/ml) is described. Subtotal gastrectomy was performed,
      and a month after surgery the level of serum AFP fell rapidly to within normal
      limits. Histologically, two types of cells coexisted in the tumor: medullary-type
      cells resembling trabecular-type hepatocellular carcinoma, and moderately
      differentiated adenocarcinoma cells. The cells of the former type were arranged
      mostly in a trabecular pattern with bile granules, but also showed a scirrhous
      pattern in a restricted area. Immunohistochemistry demonstrated that both types
      of tumor cells stained positively for AFP. This tumor, which should be classified
      as a hepatoid adenocarcinoma of the stomach, is of interest because of its
      rarity, bile secretion (indicating marked differentiation toward a hepatocyte
      form), and two cellular arrangements-trabecular and scirrhous.

PMID- 8884328
TI  - Portal tumor thrombi due to gastric cancer.
AB  - A patient with a primary gastric carcinoma complicated with a tumor thrombus in
      the portal vein is described. Pancreatoduodenectomy with tube pancreatostomy was
      performed. The location and size of tumor thrombi in the portal vein could be
      determined accurately by intraoperative ultrasonography and removed with the wall
      of the portal vein and superior mesenteric vein. There was no evidence of
      recurrence one year after the operation. Tumor thrombus in the portal vein in
      gastric cancer is rarely reported and has a poor prognosis. If there is no
      associated liver metastasis, aggressive surgical approach followed by appropriate
      chemotherapy may prolong the life of the patient.

PMID- 8884329
TI  - The rupture of hepatic hydatid disease into the right hepatic vein and bile
      ducts: a case report.
AB  - Echinococcus granulosus and Echinococcus multilocularis cause liver hydatid
      disease. One of its most common complications is rupture into the bile ducts;
      however, penetration of a cyst into a vessel is a very rare complication. We
      detected a defect (2 x 1 cm) on the wall of the right hepatic vein, in addition
      to three distinctive ruptures into the bile ducts, in our case. For systemic
      hypotension due to a bleeding during operation and to repair the vessel wall
      defect, an urgent right thoracotomy followed by a radial phrenotomy was needed.
      We were able to reach the operation site easily and repaired the vessel wall with
      polypropylene suture. Because of the occurrence of these two complications
      together and the difficulties of the operation, we decided to report this case.

PMID- 8884330
TI  - Inflammatory pseudotumor of the liver presenting as incidentaloma: report of a
      case and review of the literature.
AB  - Inflammatory pseudotumors of the liver represent a rare entity in the world
      literature, only 53 cases have been reported previously. Patients present with
      fever, upper abdominal pain, and weight loss. The finding is usually mistaken as
      a malignant lesion. Therefore most of the reported patients (77.4%, n = 41)
      underwent surgical therapy including major liver resections in 30 cases, wedge
      resections in 5 cases, and liver transplantation in 1 case. Only 12 patients
      (22.6%) were treated conservatively or were observed. We report the case of a 32
      year-old woman with the incidental sonographic finding of a hepatic lesion. After
      contradictory findings in abdominal CT, MRT and hepatic scinti-scans, the
      diagnosis of an inflammatory pseudotumor could finally be confirmed by
      laparoscopic guided needle-biopsy. The clinical course of the patient was
      completely uneventful under observation. Clinopathological features, diagnostic
      findings, therapeutical options and outcome are discussed reviewing the cases
      reported in world literature.

PMID- 8884331
TI  - Amineptine induced liver injury. Report of two cases and brief review of the
      literature.
AB  - Two cases of amineptine induced liver injury in patients treated with the drug
      for 18 and 15 days respectively, are reported. Hepatic reaction lasted 60 days in
      the first case and 120 days in the second one, with the latter considered
      unusually prolonged. The patients history, the course of the reaction and the
      histologic findings were compatible with the diagnosis of drug induced liver
      disease in both cases. Furthermore, every other possible origin of hepatobiliary
      injury such as disorders of bile ducts, ongoing viral hepatitis and autoimmune
      hepatitis were excluded. The mechanism of amineptine induced liver injury and the
      influence of a possible genetic predisposition to amineptine hepatotoxicity are
      also discussed.

PMID- 8884332
TI  - Arterioportal fistula and hemobilia with associated acute cholecystitis: a
      complication of percutaneous liver biopsy.
AB  - Complications attributable to percutaneous liver biopsy, including hemobilia and
      arterioportal fistula, are uncommon. In this report, we present the case of a
      patient who underwent percutaneous liver biopsy and, as a consequence of this
      procedure, developed an arterioportal fistula and hemobilia with associated acute
      cholecystitis. The diagnosis of hemobilia was possible with abdominal ultrasound
      and upper endoscopy, but the patient required cholecystectomy. Hepatic
      angiography was performed, demonstrating the arterioportal fistula and hemobilia.
      Transcatheter embolization occluded the fistula, resolving the hemobilia. We
      recommend ultrasound and upper endoscopy as initial diagnostic procedures, but
      angiography and selective embolization must not be delayed if arterioportal
      fistula and/or hemobilia is suspected since these measures may help to prevent
      further complications.

PMID- 8884333
TI  - Intrahepatic biliary cystadenoma demonstrated by intraoperative cholangiography.
AB  - Biliary cystadenomas are rare neoplasms usually found in the liver. These
      neoplasms have a strong tendency to recur and undergo malignant transformation,
      and so differentiating between cystadenomas and other cystic lesions of the liver
      is very important. We describe herein the characteristics of these neoplasms and
      report the first case of an intrahepatic biliary cystadenoma being demonstrated
      by intraoperative cholangiography. In our case, intraoperative cholangiography
      was very useful in differentiating a cystadenoma or cystadeno-carcinoma from
      other cystic mass lesions of the liver. Not only did it reveal a communication
      between the intrahepatic bile duct and the cystadenoma, but it also allowed
      obtain fluid for cytology.

PMID- 8884334
TI  - Biliary cystadenocarcinoma resected by segment 3 and 4 hepatectomy.
AB  - We describe a case of biliary cystadenocarcinoma of the liver in a 72 year-old
      woman presented to our hospital with abdominal fullness. Laboratory data showed
      an elevation of alkaline phosphatase and a decreased excretion of Indocyanine
      green (ICG). CT revealed a cystic tumor with papillary projections, measuring 13A
      approximately 15cm, in the left medial segment of the liver (S4). Percutaneous
      transhepatic cholangioscopy (PTCS) disclosed the tumor in the dorsal subsegmental
      duct of S4 and the cholangioscopic biopsy from the tumor revealed papillary
      adenocarcinoma. PTCS showed the left lateral posterior segmental bile duct (B2)
      joined the common tract of the left medial (B4) and left lateral anterior (B3)
      segmental bile duct, and the tumor involved B4 and B3 but not the common tract of
      B4 and B3. A radical surgery, which included segment 4 and 3 resection with
      preservation of the left hepatic duct and the segment 2 was performed. The
      histopathological examination revealed that the tumor did not involve the liver
      parenchyma and had no lymph node metastasis. Postoperative course was
      unremarkable and the patient at present time, 4 years after the operation, is
      doing well. This case report discusses the importance of preoperative evaluation
      by PTCS for a rational surgical procedure.

PMID- 8884335
TI  - Two long-term survivors after microwave coagulation therapy for hepatocellular
      carcinoma: a case report.
AB  - We present two long-term survivors who underwent microwave coagulation therapy
      (MCT) for hepatocellular carcinoma (HCC). One patient was a 55-yr-old man having
      a solitary HCC of 25 mm in diameter associated with advanced liver cirrhosis. He
      underwent MCT instead of hepatic resection because he developed bleeding tendency
      during surgery. The other patient was a 78-yr-old woman having a 7 cm tumor in
      segment II and a 15 mm satellite lesion in segment IV. Because manipulation of
      the left hepatic lobe caused prolonged hypotension, only the main tumor was
      resected. The satellite lesion was treated with MCT. In both cases, tumors and
      surrounding liver parenchyma were widely coagulated. Postoperative courses were
      uneventful. The coagulated area shrank subsequently after surgery. Both patients
      are alive 39 and 55 months after MCT without tumor recurrence. This report proves
      that MCT is a curative treatment and an alternative to hepatic resection in
      selected patients with HCCs.

PMID- 8884336
TI  - A successful treatment for hepatocellular carcinoma with atrial tumor thrombus.
AB  - A 66-year-old man with an advanced hepatocellular carcinoma and tumor thrombus
      extending into the right atrium was treated by transcatheter arterial infusion of
      lipiodol and aclarubicin. This brought about a remarkable reduction of the tumor
      and the disappearance of the right atrial tumor thrombus. The tumor was then
      radically resected by hepatic posterior segmentectomy with combined resection of
      the right hepatic vein, where the tumor thrombus remained. He is doing well
      without any signs of recurrence 22 months after the operation.

PMID- 8884337
TI  - Hepatic recurrence of cholangiolocellular carcinoma: report of a case.
AB  - We present a rare case of hepatic recurrence of cholangiolocellular carcinoma in
      a 61-year-old woman. The patient's past history included a right hepatic
      lobectomy and a hepatic hilar resection with hepaticojejunostomy for
      cholangiolocelluar carcinoma in 1990. After the diagnosis of hepatic recurrence
      in 1993, a partial hepatic resection was performed. The gross specimen showed an
      irregularly shaped white nodular tumor 2.5 cm in size without liver cirrhosis.
      The histopathological findings revealed small cuboidal cells resembling
      cholangiole forming acinar structures with fibrotic stroma, these findings were
      the same as those in the previously resected tumor. An immunohistochemical
      examination showed a positive reaction to carcinoembryonic antigen and keratin.
      The ultrastructural features revealed small round nuclei, flat contact of the
      cell membranes without interdigitation resembling that of hepatocytes, relatively
      numerous intracytoplasmic filaments, few organelae and a basement membrane
      resembling those of the bile duct epithelium. No recurrence has been observed
      during a one-year follow up. On the basis of the characteristic clinical and
      histopathological features of this case, we therefore consider that
      cholangiolocellular carcinoma should be recognized as an intermediate type
      somewhere between hepatocellular and cholangiocellular carcinoma.

PMID- 8884338
TI  - Leiomyosarcoma occurring in the ligamentum teres of the liver: a case report and
      a review of seven reported cases.
AB  - We treated a 49-year-old male with leiomyosarcoma of the ligamentum teres of the
      liver. Preoperative hepatic imagings revealed a mass in the median segment of the
      liver. The patient underwent surgery, and the mass, measuring 6x5cm in size, was
      pathologically diagnosed as leiomyosarcoma arising from the ligamentum teres. To
      our knowledge, only eight cases of this rare tumor have been reported to date in
      the English literature.

PMID- 8884339
TI  - Severe graft versus host disease following liver transplantation confirmed by PCR
      HLA-B sequencing: report of a case and literature review.
AB  - A case of severe graft versus host disease in a liver transplant recipient is
      presented. Due to HLA similarity between donor and recipient, the demonstration
      of cellular chimerism had to be made by PCR-HLA-B sequencing. In addition, we
      review the literature on this entity emphasizing its poor outcome, the difficulty
      of the differential diagnosis, and the need for the development of new
      prophylactic and therapeutic strategies in its management.

PMID- 8884341
TI  - A case of hepatocellular carcinoma in HIV-infected patient.
AB  - Persistent human immunodeficiency virus (HIV) infection induces an immuno
      suppressive state and therefore malignant tumors are a very common complication.
      Hepatocellular carcinoma is very rare, however, because it is associated with
      chronic liver disease by the persistent infection of hepatitis B or C virus (HBV
      or HCV). We reported a case of HCC with HIV infection who had no evidence of HBV
      or HCV infection, and that had a rapid growth and active pulmonary metastases.
      Pathological findings of the resected liver showed moderately differentiated HCC
      and no chronic liver disease. Despite efforts to find potential HBV integration
      in tumor and non-tumor tissue, none was observed. To our knowledge, this is the
      first report of HCC in HIV-infected patient with no evidence of hepatitis virus
      infection.

PMID- 8884340
TI  - Minute hepatocellular carcinoma originating in the caudate lobe with a long-term
      surviving of 9 years 6 months after surgical resection: a case report.
AB  - An extremely rare case of minute hepatocellular carcinoma originating in the
      caudate lobe who was resected and surviving for 9 years 6 months is presented. A
      52 year-old male patient was diagnosed as having a minute hepatocellular
      carcinoma originating in the caudate lobe by lipiodol computed tomography and
      celiac angiography. Although the caudate lobectomy was successfully performed,
      refractory ascites developed for 4 months after surgical procedure. After
      remission of ascites, the patient is well and surviving for 9 years 6 months
      without recurrence of hepatocellular carcinoma. This case suggests that early
      detection and treatment of hepatocellular carcinoma can lead to a long-term
      survival even when the caudate lobe of the liver is involved.

PMID- 8884342
TI  - Hepatoblastoma in adult age: a report of two cases.
AB  - Hepatoblastoma in adults is a rare malignancy that presents in the epithelial or
      mixed epithelial-mesenchymal variants. We report two cases, the former
      representing the epithelial and the latter the mixed type. A 21 year-old woman
      with epigastric pain had abdominal ultrasound and CT scans showing a large
      hepatic mass. A right trisegmentectomy was performed. The first and second
      recurrences were treated by resection. The third recurrence was treated by
      hepatic transarterial chemo-embolization, systemic chemotherapy and 19
      percutaneous alcohol injections. A careful follow up by abdominal ultrasound and
      CT scans was able to detect the recurrence at an early stage. The patient is well
      at 151 months. A 39 year-old man with epigastric pain and dyspepsia had upper-GI
      series and abdominal CT scan showing a left hepatic mass involving the stomach.
      Liver resection and Billroth II hemigastrectomy were performed. A recurrence
      involving the left hepatic lobe, the spleen and the remaining stomach occurred 15
      months later and the patient died from multi organ failure. Surgery is the
      treatment of choice of hepatoblastoma in adults. Recurrences can also be treated
      aggressively by surgical resections if no extrahepatic organs are involved. Other
      therapeutic modalities can be attempted whenever surgery is not possible.

PMID- 8884343
TI  - Case of small hepatocellular carcinoma in the caudate lobe detected after
      interferon caused disappearance of hepatitis C virus.
AB  - The high prevalence of antibodies to hepatitis C virus (HCV) in patients with
      hepatocellular carcinoma (HCC) in Japan suggests that the virus has a close
      relationship to hepatocarcinogenesis (1-4). HCV causes chronic inflammation of
      the human liver and HCC may finally develop, by way of an unknown mechanism.
      Interferon (IFN), which has an antiviral effect, is widely used for treatment of
      chronic hepatitis C infection (5). In Japan, about 40% of such patients have been
      cured of the infection by IFN therapy (6). The most suitable criteria for
      identification of a complete response to IFN are the most rigorous: both the
      disappearance of HCV RNA, verified by the polymerase chain reaction (PCR), and
      alanine aminotransferase activity in the normal range for at least six months
      after the end of the therapy. In the cured patients, the liver disorder and
      hepatocarcinogenesis are thought to stop progressing. However, few such patients
      have been monitored for years following the treatment (7-8). In this article, we
      describe a patient with small HCC in the caudate lobe after complete response to
      IFN therapy for chronic hepatitis. We suggest the necessity for regular liver
      checks for patients from whom HCV is eliminated by IFN therapy.

PMID- 8884345
TI  - Gardner's syndrome in several family members.
AB  - This article describes chronologically a case of a fatal hereditary disease,
      which manifests itself in multiple polyps in the large intestine, accompanied by
      the appearance of numerous mesenchymal tumors on and under the skin and in the
      bones. In the Internal Department of the General Hospital Murska Sobota, we
      diagnosed the disease in one member of the family; in another, we ascertained the
      illness was retrograde. We confirmed the two cases in our dispensary; one of them
      remains under the constant surveillance of a gastroenterologist. The disease was
      in an advanced stage in the two family members at the time of discovery, so the
      treatment was radical. Nevertheless it terminated fatally. We expect to undertake
      future radical surgical measures on the other member in whom the disease was
      diagnosed. In this article, we illustrate the course of Gardner's Syndrome (GS),
      where in spite of early diagnoses, which now begin with molecular genetics and
      continues to endoscope examinations, and radical operative intervention, the
      quality of life of the patient is not improved to any great degree. The patient
      represents an exceptionally high risk group for the development of other
      mesenchymal tumors growths and colorectal cancer. The open question is also what
      is surgical treatment: total colectomy or proctocolectomy and what to do with the
      ileum when it is full of polyps.

PMID- 8884344
TI  - Spontaneous recovery of post partus liver necrosis in a patient listed for
      transplantation.
AB  - The patient was a young previously healthy woman, who after a normal grosses,
      during delivery got severe abdominal pain. The liver function tests were highly
      pathological and the patient became anuric and developed first grade of
      encephalopathy. In computer tomography, 90% of the liver parenchyma was damaged
      and liver biopsy showed necrosis. The patient had fulminant hepatic failure
      including hepatorenal syndrome and was put on the Scandiatransplant high urgent
      waiting list for a liver transplant. No suitable liver was found. After eight
      days, the general situation of the patient was better and the liver function
      tests started to improve. She was taken off the waiting list. Twenty-seven days
      after delivery the patient was discharged in good condition. At check up six
      months later the patient was feeling well and the clinical tests were normal.

PMID- 8884346
TI  - Gastric cancer.

PMID- 8884347
TI  - Monocytoid/marginal zone B-cell differentiation in follicle centre cell lymphoma.
AB  - We report on two cases of low grade follicle centre cell lymphoma with a
      pronounced parafollicular monocytoid/ marginal zone B-cell component. One patient
      had a history of preceeding follicular high grade B-cell lymphoma of
      centroblastic type showing the same light chain restriction and identical
      immunoglobulin heavy chain gene rearrangement as the low grade lymphoma diagnosed
      15 months later. Morphologically, in both cases the two constituents of the low
      grade tumours were clearly distinguishable. Immunohistochemically, the follicular
      component strongly expressed bcl-2 protein in contrast to a weak staining of the
      marginal zone B-cell component. Performing PCR, a rearrangement of the major
      breakpoint region of bcl-2 was not found. Identical light chain restriction of
      the follicular and the monocytoid B-cell/marginal zone components strongly
      indicates a clonal relationship between them. A monocytoid/marginal zone B-cell
      component in follicular lymphoma probably results from differentiation of the
      follicle centre cells and does not indicate a composite lymphoma.

PMID- 8884348
TI  - Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use
      in the diagnosis of malignant mesothelioma.
AB  - The aim of this study was to examine the expression of three putative
      mesothelioma-binding antibodies, thrombomodulin, OV 632 and HBME-1 in 42
      malignant mesotheliomas (27 pleural and 15 peritoneal) and 32 pulmonary
      adenocarcinomas. Evaluation of their use in differentiating between the
      mesotheliomas and pulmonary adenocarcinomas was assessed. Thrombomodulin was
      expressed by 22 of 42 (52%) mesotheliomas but was seen in eight of 12 pure
      epithelial-type mesotheliomas of the pleura and in all four papillary epithelial
      peritoneal mesotheliomas. For pure epithelial mesotheliomas thrombomodulin was
      75% sensitive. Only two of 32 pulmonary adenocarcinomas were immunoreactive
      yielding a 94% specificity for thrombomodulin. In comparison, OV 632 and HBME-1
      showed 67% and 62% antibody sensitivity, respectively, for malignant mesothelioma
      but this was accompanied by low specificity (OV 632, 37%; HBME-1, 28%). Both OV
      632 and HBME-1 are considered unsuitable for use in differentiating between
      mesotheliomas and pulmonary adenocarcinomas. We advocate the use of
      thrombomodulin as a mesothelioma-binding antibody in the standard panel of
      antibodies used in the evaluation of malignant mesothelioma.

PMID- 8884349
TI  - Proliferation, ploidy and prognosis in uterine smooth muscle tumours.
AB  - DNA ploidy, mitotic rate (per 10 high power fields), mitotic index (per 1000
      tumour nuclei), Ki-67 labelling index and S phase fraction were measured in 23
      uterine leiomyosarcomas and 10 tumours of uncertain malignant potential.
      Correlations were calculated by Spearmann rank correlation. Univariate survival
      analysis was performed by log rank analysis and multivariate analysis performed
      by the Cox linear regression method. Ki-67 index and S phase fraction were
      significantly higher in leiomyosarcomas than in tumours of uncertain malignant
      potential. There was significant correlation between mitotic rate, mitotic index,
      Ki-67 index and S phase fraction in cases of leiomyosarcoma. Fifteen of 22
      leiomyosarcomas and one of 10 tumours of uncertain malignant potential were DNA
      aneuploid. On univariate analysis of all the smooth muscle tumours, DNA ploidy,
      presence of significant nuclear atypia and presence of coagulative tumour cell
      necrosis were associated with outcome. Only DNA ploidy was associated with
      outcome in the group of leiomyosarcomas. On multivariate analysis of all of the
      smooth muscle tumours, DNA ploidy, age and grade of atypia were independently
      associated with outcome. No single factor was independently predictive of outcome
      in the group of leiomyosarcomas. Alternative indices of cell proliferation
      correlate with mitotic rate in uterine leiomyosarcoma and do not provide
      additional useful prognostic information. DNA ploidy, age and grade of atypia are
      independently associated with outcome in uterine smooth muscle tumours and
      measurement of DNA ploidy may be useful in identification of cases with an
      adverse prognosis.

PMID- 8884350
TI  - Massive arterial haemorrhage from the lower gastrointestinal tract.
AB  - We have studied the clinical, radiological and pathological features of three
      patients with recurrent massive lower gastrointestinal arterial haemorrhage. Case
      1 was an example of Dieulafoy's vascular malformation within the proximal
      ascending colon in a 46-year-old woman. Cases 2 and 3 were men aged 81 and 83
      years with arterial erosions contained within small mucosal diverticula in the
      hepatic flexure and descending colon, respectively. All three patients presented
      with recurrent acute episodes of massive lower gastrointestinal haemorrhage.
      Selective mesenteric angiography was performed in cases 1 and 3 to localize the
      bleeding point in both patients. The features were very different to those of
      angiodysplasia, lacking the tuft of abnormal vessels and the early venous filling
      phase commonly seen in the latter condition. The patients were all successfully
      treated by partial colectomy. The aetiology of Dieulafoy's vascular malformation
      remains unclear. The ruptured arteries in cases 2 and 3 shared many histological
      features with the Dieulafoy lesion in case 1. The lesions in cases 1 and 2 were
      associated with recent oral non-steroidal anti-inflammatory therapy, suggesting
      coincidental mucosal ulceration as a contributory factor.

PMID- 8884351
TI  - Immunohistochemical differentiation of metastatic breast carcinomas from
      metastatic adenocarcinomas of other common primary sites.
AB  - To test the possibility of immunohistochemical differentiation of cytostatically
      treatable metastatic breast carcinomas from other metastatic adenocarcinomas of
      unknown primary site, we studied a total of 328 metastatic adenocarcinomas
      including 35 bronchogenic, 26 pancreatic, 25 colonic, 39 gastric, 45 renal, 29
      ovarian and 129 breast carcinomas with a panel of 13 commercially available
      monoclonal antibodies. The expression of gross cystic disease fluid protein 15
      and/or oestrogen or progesterone receptors had a sensitivity of 0.83, a
      specificity of 0.93 and a predictive accuracy of 0.92 for carcinomas of the
      breast against all other carcinomas. Excluding ovarian carcinomas, this
      combination had a sensitivity, specificity and predictive accuracy for mammary
      carcinomas of 0.83, 0.98 and 0.98, respectively. Carcinoembryonic antigen and/or
      cytokeratin 20 identified bronchogenic, gastric, pancreatic and colorectal
      carcinomas versus breast carcinomas lacking gross cystic disease fluid protein 15
      and oestrogen or progesterone receptors with a sensitivity, specificity and
      predictive accuracy of 0.82, 0.99 and 0.95, respectively. Vimentin differentiates
      renal cell carcinomas from gross cystic disease fluid protein 15 and oestrogene
      or progesterone receptor negative breast carcinomas with a sensitivity,
      specificity and predictive accuracy of 0.93, 0.82 and 0.84. Thus, it should be
      possible to differentiate most metastatic mammary carcinomas from metastatic
      adenocarcinomas of other common primary sites, even if the former lack expression
      of gross cystic disease fluid protein 15 and oestrogen or progesterone receptors.

PMID- 8884352
TI  - Medullary breast carcinoma vs. poorly differentiated ductal carcinoma: an
      immunohistochemical study with keratin 19 and oestrogen receptor staining.
AB  - Sixty breast carcinomas previously indexed as medullary carcinomas over a 24-year
      period were reviewed and reclassified according to definitions suggested by
      Ridolfi et al. as typical medullary carcinoma, atypical medullary carcinoma, and
      non-medullary carcinoma. Paraffin sections of tumour tissue were examined by an
      avidin-biotin complex method using two keratin 19-specific monoclonal antibodies
      (BA17, DAKO and clone 170-2-14, Boehringer) and a monoclonal oestrogen receptor
      antibody (DAKO). For comparison 52 ductal carcinomas of grade II and grade III
      were immunostained as well. The results showed that all 60 tumours with medullary
      features and all 52 ductal carcinomas reacted moderately to strongly positive
      with anti-keratin 19 (Boehringer). The staining was diffuse in all cases, except
      one case of ductal carcinoma (grade III), which stained focally. Immunostaining
      with the second keratin 19 antibody (BA17) revealed similar results with positive
      staining in 59 (95%) cases of carcinomas with medullary features and 51 (98%)
      cases of ductal carcinomas. Only one case in each group did not express keratin
      19 (BA17), one re-classified case of non-medullary carcinoma with neuroendocrine
      features and one case of ductal carcinoma of grade III. None of the 13 cases of
      typical medullary carcinoma were oestrogen receptor positive and only seven (12%)
      of the carcinomas with medullary features (2 atypical, 5 non-medullary) were
      oestrogen receptor positive with quantitative values from 20 to 100%. The 52
      ductal carcinomas of grade II and III were oestrogen receptor positive in 56% and
      47% of cases. It is concluded that keratin 19 staining is of no particular value
      in differentiating medullary from poorly differentiated ductal carcinoma. A
      carcinoma with positive oestrogen receptor staining is not likely to be a typical
      medullary carcinoma.

PMID- 8884353
TI  - Neural variant of fetal rhabdomyoma and naevoid basal cell carcinoma syndrome.
AB  - A 15-year-old boy with the characteristic features of the naevoid basal cell
      carcinoma syndrome presented with a retroperitoneal mass. The tumour showed
      morphological features of a still ill-defined variant of fetal rhabdomyoma,
      characterized by well-differentiated nerve fibres admixed with immature striated
      muscle cells, similar to neuromuscular choristoma. Four cases of fetal
      rhabdomyoma and naevoid basal cell carcinoma syndrome have been previously
      reported. The behaviour of this tumour has been benign, although a complete
      excision was impossible due to its close relation with abdominal vascular trunks.

PMID- 8884354
TI  - Gynandroblastoma of ovary with juvenile granulosa cell component and heterologous
      intestinal type glands.
AB  - An ovarian gynandroblastoma in a 15-year-old girl is described. The predominant
      component was juvenile granulosa cell tumour. Areas of adult granulosa cell
      tumour and Sertoli cell elements were also present. Stromal theca and luteinised
      cells were identified. An additional histological finding was the presence of
      heterologous intestinal type glands. There was positive immunohistochemical
      staining of juvenile and adult granulosa cell areas with inhibin and MIC2
      antibodies. Electronmicroscopy showed a close ultrastructural resemblance between
      tumour cells in granulosa and Sertoli cell areas, in spite of differences in
      architectural pattern, suggesting that both morphological components may derive
      from a single cell of origin. The tumour demonstrates a unique combination of
      elements which has not previously been described.

PMID- 8884356
TI  - Primary spinal epidural manifestation of malignant lymphoma.
AB  - The clinical, histological and immunomorphological data in 19 cases of primary
      spinal epidural manifestation of malignant lymphomas collected between 1974 and
      1994 are reported. The age of the patients varied between 11 and 87 years with a
      mean age of 56.3 years. There was a slight male predominance (11:8). In most
      cases, the onset of the clinical symptoms was rapid. The preferential tumour
      localization was the epidural space related to the thoracal vertebral bone. In
      each case, decompressive laminectomy was performed. The tumours were
      histologically and immunomorphologically classified as B-cell lymphomas (14 of
      19), T-cell lymphomas (3 of 19) and anaplastic plasmacytoma (1 of 19). Except for
      one case, post-operative staging did not reveal anything other than epidural
      manifestation of the malignant lymphoma. The vertebral bone, however, was
      involved in seven cases. Irradiation alone, or in combination with chemotherapy,
      was performed as additional therapy. The post-operative survival time was
      variable.

PMID- 8884355
TI  - Fusocellular gonadal stromal tumour of the testis with epithelial and myoid
      differentiation.
AB  - We describe an unusual fusocellular gonadal stromal tumour with a benign
      behaviour in the left testis from a 16-year-old man. The neoplasm consisted of a
      non-encapsulated proliferation of irregularly arranged, fusiform cell bundles in
      fibrous connective tissue. The tumour cells contained a slightly infolded
      nucleus, some dilated rough endoplasmic reticulum cisternae, abundant filament
      bundles which connected to subplasmalemmal electron-dense bodies, pinocytotic
      vesicles and a discontinuous basal lamina. The intercellular spaces were narrow
      and the tumour cells were joined by desmosomes. These cells were immunoreactive
      for muscle actin, alpha-actinin and vimentin. Focal immunostaining for collagen
      type IV was observed around the cells. No immunoreactivity for keratins, desmin S
      100 protein or XIIIa factor was found. The findings suggest that the tumour arose
      from the peritubular myoid cells.

PMID- 8884357
TI  - Foamy cell aggregation in duodenal diverticula.
AB  - We have investigated 44 cases of duodenal diverticulum to delineate the
      pathological features. Foamy cell aggregations were observed in 24 (54.5%) of the
      cases. The foamy cells were located within the submucosa in all 24 cases and were
      found around the deepest portion of the diverticula in 14. There were no
      statistically significant differences between the depth of the diverticulum and
      the presence or degree of foamy cell aggregation. Lymphoid aggregates, focal
      thickening of the muscularis mucosae, submucosal fibrosis, intimal thickening of
      submucosal vessels and submucosal haemorrhage were also detected, but statistical
      analysis showed no significant associations between these pathological findings
      and the presence of foamy cell aggregates. We conclude that the foamy cell
      aggregates are a non-specific but frequent pathological finding in duodenal
      diverticula and which have not been described in previous studies.

PMID- 8884358
TI  - Pulmonary capillary haemangiomatosis.

PMID- 8884359
TI  - Metastasising sarcoma of the aorta.

PMID- 8884360
TI  - Diffuse malignant mesothelioma arising in a paracolostomy hernial sac.

PMID- 8884361
TI  - Primary low grade malignant lymphoma of mucosa-associated lymphoid tissue of
      gallbladder.

PMID- 8884362
TI  - Bone marrow granulomas in hairy cell leukaemia.

PMID- 8884363
TI  - T-cell rich B-cell non-Hodgkin's lymphoma: a progressed form of follicle centre
      cell lymphoma and lymphocyte predominance Hodgkin's disease.

PMID- 8884364
TI  - Determinants of Helicobacter pylori pathogenicity.
AB  - Helicobacter pylori is a recently recognized bacterial pathogen associated with
      diverse pathologies of varying severity, such as chronic gastritis, peptic
      ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric
      carcinoma. We here present a review of our current knowledge on the properties of
      H. Pylori that adapt it to its particular niche by allowing it to survive in the
      stomach and to colonize the gastric mucosa, as well as those that underlie its
      persistence and pathogenicity. While the bacterial determinants that preclude the
      persistent colonization of the gastric mucosa are better understood, those
      associated with pathogenicity appear to result from the possibility for some of
      the bacteria of the species to synthesize products that directly or indirectly
      damage the gastric mucosa, cause a persistent inflammatory reaction, and/or
      perturb the regulation of acid secretion.

PMID- 8884365
TI  - Distribution of HHV-6 variants in human tissues.
AB  - Human herpesvirus (HHV)-6 strains segregate into two variants (HHV-6A and HHV
      6B), closely related to each other but clearly and easily distinguishable. These
      two HHV-6 variants differ in their ability to grow in T-cell lines, have
      distinctive patterns of DNA restriction fragments, and show specific reactivities
      with some monoclonal antibodies. The degree of DNA homology between variants
      ranges from 97% in the most conserved region to 75% in the immediate early region
      1. HHV-6B is the etiologic agent of exanthema subitum but HHV-6A has not yet been
      clearly associated with any human pathology. HHV-6 sequences are frequently
      detected by the polymerase chain reaction (PCR) in healthy and pathological
      tissues. HHV-6B is more prevalent in peripheral blood mononuclear cells and in
      lymphatic tissue. The prevalence of HHV-6A may be greater in some pathological
      conditions such as Kaposi's sarcoma, and in skin biopsies. Results so far
      available support the hypothesis that HHV-6 variants may have different
      epidemiologies.

PMID- 8884366
TI  - Kaposi's Sarcoma (KS)-associated herpesvirus and its role in KS.
AB  - Epidemiologic studies have long suggested that Kaposi's sarcoma (KS) is caused by
      a sexually transmissible infectious agent. A new, and presumably human,
      herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), has been
      detected in KS lesions from AIDS patients by sequence-based detection techniques.
      KSHV is present in almost all KS lesions from all forms of KS. The virus is a
      Rhadinovirus or gamma-2 herpesvirus most closely related to Herpesvirus saimiri
      (HVS), and possesses several genes that may allow it to modify its host cell
      environment. KSHV has been isolated in vitro with immortalized B cell lines
      derived from a second malignancy associated with KSHV, body cavity-based
      lymphomas (BCBL). Epidemiologic studies performed to date indicate that KSHV,
      unlike other human herpesviruses (HHV), is not ubiquitous. The growing body of
      evidence indicates that KSHV is a potent oncogenic herpesvirus and the likely
      infectious cause of KS and BCBL.

PMID- 8884367
TI  - Lymphocytes from site of disease indicate probable microbiological etiology of
      "infective-immune" diseases such as rheumatoid arthritis.
AB  - Synovial lymphocytes, from the site of disease, by their response to
      microbiological antigen stimulation as measured by the [3H]thymidine uptake
      method, indicate the microbiological causes of reactive arthritis and also
      oligoarthritis unassociated with enteric or genital symptoms. In the study of the
      etiology and pathogenesis of rheumatoid arthritis, the application of the same
      procedures gives an indication that the disease is an immune response to a
      variety of common infective agents, both viral and bacterial. The demonstration
      of antigens or nucleic acid of an infective agent at the site of disease, in
      association with a specific local immune response suggests the pathogenetic
      importance of the agent. Recent studies of relationships between epitopes of
      infective agents and MHC gene products suggest several ways in which infective
      agents can directly cause a disease such as rheumatoid arthritis without any
      requirement for autoimmune contributions. Because the infective agent may be the
      primary determining factor and the one most amenable to correction or
      eradication, the term "infective-immune" is suggested in preference to
      "autoimmune" for these immune-mediated diseases.

PMID- 8884368
TI  - The pathogenesis of AIDS: lessons learned from other medical conditions.

PMID- 8884369
TI  - Immunization strategy for prevention of congenital cytomegalovirus infection.
AB  - Women of childbearing age are a logical target for a vaccine aimed at prevention
      of congenital cytomegalovirus (CMV) infections. However, the impact of a CMV
      vaccine could likely be enhanced by considering the sources of maternal infection
      and characteristics of mothers of infected newborns. Contact with preschool-age
      children and sexual activity are important sources of CMV infection for young
      women. Approximately half of infants with congenital CMV infection in the U.S.
      are born to unmarried, adolescent mothers. To prevent CMV infection in those who
      are the sources of maternal infection as well as in young, unmarried mothers,
      universal immunization of toddlers and preteen children should be considered.

PMID- 8884370
TI  - Aspergillus infections: problems in diagnosis and treatment.

PMID- 8884371
TI  - Structural plasticity of the adult CNS. Negative control by neurite growth
      inhibitory signals.
AB  - The neuronal network of the adult central nervous system (CNS) retains a limited
      capacity for growth and structural change. This structural plasticity has been
      best studied in the context of lesion-induced growth and repair. More recently,
      structural changes underlying functional plasticity occurring under specific
      physiological conditions have also been documented, in particular in the cortex
      and the hippocampus. Areas known for their adult plastic potential retain high
      levels of the growth associated protein GAP-43, suggesting a persistence of
      important components of the intracellular growth machinery throughout life.
      Interestingly, a pronounced negative correlation exists between the levels of GAP
      43 and myelination in the adult CNS. Because CNS myelin contains potent neurite
      growth inhibitory membrane proteins, neurite growth, sprouting and plasticity
      were investigated in the spinal cord and brain in areas where oligodendrocyte
      development and myelin formation was experimentally prevented, or in the presence
      of an inhibitor neutralizing antibody (mAB-IN-1). In all areas, lesion-induced or
      spontaneous sprouting was enhanced, in parallel with persistent high levels of
      GAP-43. Thus, spontaneous sprouting of side branches occurred from retinal axons
      in the optic nerve in the absence of myelin, and target-deprived retinal axons
      showed increased sprouting and innervation of the contralateral optic tectum in
      the presence of mAB IN-1. In experimentally myelin-free spinal cords collaterals
      from intact dorsal roots grew over long distances to innervate deafferented
      target regions following the section of three dorsal roots. Similarly, the
      corticospinal tract sprouted across the the midline and re-established a dense
      plexus of fibres on the contralateral side of the spinal cord following section
      of one corticospinal tract in juvenile rats. Following bilateral dorsal
      hemisection of the spinal cord including both corticospinal tracts in young and
      adult rats, long distance regeneration of corticospinal fibres leading to
      significant functional improvements of locomotion and certain reflexes was
      induced by the neurite growth inhibitor neutralizing antibody IN-1.

PMID- 8884372
TI  - Growth stimulation and chemotropic attraction of rat retinal ganglion cell axons
      in vitro by co-cultured optic nerves, astrocytes and astrocyte conditioned
      medium.
AB  - The effects of explants of optic nerves of different ontogenetic ages (P0 P14,
      adult), and of cultured astrocytes of various ages on the neurite regeneration of
      rat retinal ganglion cells (RGC) were assessed in vitro, using a three
      dimensional culture system which allows the co-cultivation of various explants.
      Both co-cultured P0-P12 optic nerves and astrocyte cultures from P2 cerebral
      cortex stimulated the regeneration of neurites from the retinal explants after 3
      days in culture. By contrast, P14 and older explants of the optic nerve,
      astrocytes from P17 optic nerve and astrocytes that had previously been grown in
      culture for more than 6 weeks had no effect on RGC neurite outgrowth. Moreover,
      both the P0-P12 optic nerve explants and the astrocytes from P2 cerebral cortex
      also seemed to have a chemotropic effect on the regenerating neurites, because
      the latter were longer on the side facing the co-explantat. The absence of a
      cellular bridge between retinal and optic nerve explants suggests that the
      effects are mediated by astroglia-derived diffusible neurite growth promoting
      factors. Accordingly, astrocyte-conditioned medium from P2 astrocytes also
      stimulated the outgrowth of neurites from the retinal explants. These findings
      show that immature astrocytes of a limited ontogenetic period release as yet
      unknown diffusible neurite growth-promoting factors which stimulate the
      regeneration of neurites from retinal explants.

PMID- 8884373
TI  - Effects of ischemia-hypoxia induced by interruption of uterine blood flow on
      fetal rat liver and brain enzyme activities and offspring behavior.
AB  - The effects of acute perinatal ischemia-hypoxia on fetal liver and brain energy
      metabolism, fetal brain total free fatty acid concentration and subsequent
      offspring behavior were investigated in rats. Ischemia-hypoxia was induced at
      term either by ligation of the uterine blood vessels or submersion of the entire
      uterine horn in warmed saline. Fetuses of the adjacent horn served as within-dam
      controls for all assessments and fetuses of dams which had not undergone the
      surgical stress served as independent controls for enzyme assays. Ischemia
      hypoxia was associated with reduced activity of fatty acid synthase in the liver
      and brain. Total free fatty acid concentration significantly increased in the
      fetal hypoxic brain. Pups not used for enzyme analyses were cross-fostered for
      behavioral assessments. Relative to the enzymatic alterations, there were few
      behavioral alterations associated with ischemia-hypoxia. At postnatal day 30,
      rats made hypoxic by ligation of the uterine blood vessels had decreased caudate
      nucleus and brain stem weights relative to within-dam controls. At postnatal day
      85, rats made hypoxic by submersion of the uterine horn had decreased olfactory
      bulb weight. The results of this study indicate an initial acute response to a
      brief period of ischemia-hypoxia at term pregnancy in the fetal rat brain and
      liver.

PMID- 8884374
TI  - Effect of growth factors on the in vitro growth and differentiation of early and
      late passage C6 glioma cells.
AB  - The effect of different hormones and growth factors was assayed on the in vitro
      growth and enzymatic activities of 2',3'-cyclic nucleotide 3'phosphohydrolase
      (CNP) and glutamine synthetase (GS) of rat glioma C6 cells at two different
      passages in culture. Young cultures (passage 26), mainly oligodendrocytic, and
      older cultures (passage 134), predominantly astrocytic, were treated with 10
      microM dexamethasone, 20 ng/ml transforming growth factor alpha (TGF alpha), 10
      ng/ml insulin, 20 ng/ml platelet-derived growth factor (PDGF), and 20 ng/ml,
      epidermal growth factor (EGF) in serum-free chemically defined media. In vitro
      growth rate was measured in terms of DNA content, by a fluorometric method of
      diaminobenzoic acid, and rate of DNA synthesis by 3H-thymidine incorporation. CNP
      activity (marker for in vitro oligodendrocytes) and GS activity (marker for
      astrocytes) were determined spectrophotometrically. Dexamethasone reversibly and
      significantly inhibited growth of C6 glioma in early and late passages. PDGF and
      insulin promoted in vitro growth only in late passage but not in early passage
      cells, whereas EGF and TGF alpha did not significantly affect growth. An increase
      in CNP activity was observed in early passage cells under the effect of PDGF and
      insulin. The increase in GS activity induced by insulin and dexamethasone
      suggests a differentiating role for these factors in C6 glioma cells. These
      results further present the C6 glioma cell line as a useful model for studies on
      glial cell properties and responsiveness in culture and support its use in
      experimental aging in vitro.

PMID- 8884375
TI  - DiI labeling and homeobox gene islet-1 expression reveal the contribution of
      ventral neural tube cells to the formation of the avian trigeminal ganglion.
AB  - Cells of the neural tube are thought to be committed to form only the central
      nervous system, whereas the peripheral nervous system is believed to be derived
      from neural crest cells and from placodes, which are specialized regions of the
      surface ectoderm. Neural crest cells arise early from the dorsal part of the
      neural tube. The possibility that after emigration of the neural crest cells,
      another population of cells arising from the ventral part of the neural tube also
      emigrates via a different route was examined. Here we report that, after labeling
      cells of the ventral neural tube in the rostral hindbrain of E3 duck embryos with
      DiI, they were later found in the trigeminal ganglion of the fifth cranial nerve.
      A trail of labeled cells could be traced from the ventral part of the neural tube
      to the peripheral ganglion. Further, expression of the homeobox gene Islet-1 in
      cells of the neural tube and the ganglion also indicated that some ventral neural
      tube cells may normally emigrate to the trigeminal ganglion. It is concluded that
      not all neural tube cells are committed to form the central nervous system; the
      ventral part of the neural tube also provides cells for the formation of the
      trigeminal ganglion. These results raise the possibility that the ventral neural
      tube may serve as an additional source of cells for the formation of various
      other components of the peripheral nervous system.

PMID- 8884376
TI  - Neuron-glia interrelations during migration of Purkinje cells in the mouse
      embryonic cerebellum.
AB  - The interrelations between migratory Purkinje cells and radial glial processes
      were examined immunohistochemically and electron-microscopically in the fetal
      mouse cerebellum. Migratory Purkinje cells identified immunochemically with anti
      spot 35 antibody were apposed to the presumed radial glial processes. Putative
      immature migratory Purkinje cells were apposed to the radial glial processes
      identified immunochemically with monoclonal antibody 1D11 or anti-tenascin
      antibody. Junctional specializations related to cell adhesion were observed at
      the sites of contact between the immature neurons and glial processes.
      Furthermore, coated vesicles and coated pits were noted in the contact region.
      These findings support the concept of contact guidance of migratory Purkinje
      cells by radial glial processes through cell adhesion, and also suggest the
      trophic interactions occurring at the region of contact.

PMID- 8884378
TI  - Long-term nigral transplants in rat striatum: an electron microscopic study.
AB  - The substantia nigra of gestation day 14 was transplanted into the striatum of 3
      4-month-old rats to investigate the transplants ultrastructurally at the end of 2
      years, as a follow-up to our previous studies. Transplants were of small size in
      all 10 specimens taken for this study. The changes observed in the transplant and
      in the interface region with the host striatum were: thickening of the blood
      vessel walls, perivascular cuffing with lymphocytes and macrophages loaded with
      tissue debris, degenerating neurons and hypertrophied astroglia containing dense
      granules indicating ageing or reaction to degeneration and glial processes. The
      number of surviving neurons in the transplants was small. These were smaller in
      size and had very few intracytoplasmic membraneous organelles. A higher content
      of intracytoplasmic ageing lipofuscin pigment was present than in host neurons
      and age-matched nigral neurons. Synapses were few, and their number varied among
      transplants. Generally, the synapses were at the interface with the host tissue.
      The changes observed in all the 2-year-old transplants suggest premature ageing
      or a slow rejection process. Slow rejection is a possibility, because these rats
      are only stock-bred, not inbred, and hence they are not completely
      immunologically compatible.

PMID- 8884377
TI  - Neurite outgrowth of striatal neurons in vitro: involvement of purines in the
      growth-promoting effect of myenteric plexus explants.
AB  - We have shown previously that a soluble factor(s) released by the myenteric
      plexus promotes neurite outgrowth from postnatal striatal neurons, and that this
      effect was abolished by tetrodotoxin. We have now investigated the possible
      involvement of purines in the mediation of this neuritogenic response, by
      examining their effect on neurite length of striatal neurons both in co-culture
      with myenteric plexus explants and cultured alone. Both ATP and 2-chloroadenosine
      partially reversed the inhibitory effect of tetrodotoxin in co-cultures with
      whole myenteric plexus, while the stable ATP analogue, alpha, beta-methylene ATP,
      had no effect, suggesting that ATP was being broken down to adenosine before
      exerting its action. Further support for this view was that the ATP (P2)
      purinoceptor antagonist suramin did not reverse the effects of ATP, while the
      adenosine (P1) purinoceptor antagonist 8-(p-sulphophenyl)theophylline did
      antagonize the effects of ATP in tetrodotoxin-treated co-cultures. Further, both
      8-(p-sulphophenyl)theophylline and adenosine deaminase reduced the effect of the
      myenteric plexus on striatal neurons in the absence of tetrodotoxin, and the
      adenylate cyclase activator forskolin completely reversed the effect of
      tetrodotoxin in our co-culture system. The neurite outgrowth-promoting effect of
      2-chloroadenosine in tetrodotoxin-treated co-cultures was not further enhanced by
      a combination of neuropeptides. Serotonin and GTP were without effect on striatal
      neurons in the presence or absence of myenteric plexus explants. In experiments
      without myenteric plexus, both 2-chloroadenosine and forskolin caused a slight
      increase in striatal neurite length; ATP and GTP were ineffective. Basic
      fibroblast growth factor, nerve growth factor, neurotrophin-3 or neurotrophin-4/5
      had no effect on neurite outgrowth in postnatal striatal cultures after two days
      in vitro. When these growth factors were added in combination with 2
      chloroadenosine, the observed increase in mean neurite length did not exceed that
      induced by 2-chloroadenosine alone. Both 2-chloroadenosine and the ganglioside
      mix AGF1 increased neurite elongation of striatal neurons after two days in
      vitro, but an inhibition of enhanced neurite outgrowth was observed when both
      substances were added together. Both laminin and fibronectin were not
      neuritogenic for postnatal striatal neurons under our culture conditions. These
      observations suggest that a factor other than the growth factors tested here is
      involved in the promotion of striatal neurite outgrowth in co-culture with
      myenteric plexus explants. In summary, adenosine (probably acting through the A2
      subclass of the P1 purinoceptor) leads to increased striatal neurite outgrowth in
      co-culture with myenteric plexus and we propose that it does so either (1) by
      triggering the release of a neuritogenic factor, possibly from enteric glial
      cells, or (2) by acting synergistically with such a growth factor. Adenosine acts
      via P1 purinoceptors, which leads to changes in cyclic AMP, and the response to
      forskolin suggests that cyclic AMP is probably involved in the events leading to
      increased striatal neurite outgrowth.

PMID- 8884379
TI  - Central and peripheral neurochemical alterations and immune effects of prenatal
      ethanol exposure in rats.
AB  - In contrast to the well known effects of prenatal ethanol exposure on the central
      nervous system, data about its peripheral effects are scarce. Here, Sprague
      Dawley rats were fed a liquid diet (gestational days 0-20) containing 36% ethanol
      derived calories (EDCs, group H) or were pair-fed with 18% EDCs (group L) or 0%
      EDCs (group C). On postnatal day 20, one male and one female from each of 10
      litters per group were killed. Norepinephrine (NE) was analyzed in the frontal
      cortex, spleen and thymus, and dopamine, 5-hydroxytryptamine (serotonin, 5-HT)
      and their metabolites 3,4-dihydroxyphenylacetic acid, homevanillic acid (HVA) and
      5-hydroxyindoleacetic acid (5-HIAA) were analyzed in the striatum by high
      performance liquid chromatography with electrochemical detection. Lymphocyte
      subpopulations in the spleen and thymus were also assessed in half of these
      litters. Significant decreases in splenic NE concentration were seen in both
      sexes of group H (males 27%, females 28%). Decreases in striatal 5-HT and 5-HIAA
      of group H subjects appeared to be sex specific (only females were significantly
      affected: 23% decrease in 5-HT, 37% decrease in 5-HIAA). Pronounced, dose
      dependent reductions in T cell percentages were observed in both the thymus and
      spleen. Splenic CD8+ and CD4+ cell percentages were positively correlated with
      the splenic NE concentrations. It is concluded that the decreases seen in splenic
      T cell percentages subsequent to prenatal ethanol exposure may be caused, at
      least partially, by impaired noradrenergic control of this organ.

PMID- 8884380
TI  - Exposure to perinatal morphine promotes developmental changes in rat striatum.
AB  - This study shows that perinatal exposure to morphine promotes developmental
      changes (up to 8 months of life) in the striatum by up-regulating concentrations
      of substance P and met-enkephalin with changes of prometenkephalin A mRNA
      expression at the day of birth only. Dopamine metabolism (up to 60 days) is also
      increased as suggested by the reduced concentrations of dopamine and increased
      content of 3,4-dihydroxyphenylacetic acid. Tyrosine hydroxylase mRNA expression
      is selectively reduced only in the substantia nigra by perinatal morphine.
      Serotonin content is reduced only during the early postnatal days and is
      unaffected thereafter. Supplementation of naltrexone to morphine-exposed rats
      prevents monoaminergic and neuropeptidergic changes in the striatum, which
      directly implicates opioid receptors in the developmental changes caused by
      morphine. The data suggest that perinatal morphine may inhibit met-enkephalin
      release, causing accumulation of the peptide without corresponding changes in
      specific mRNA. Dopamine release may also be increased as indicated by a higher
      metabolism and consequent reduction of tyrosine hydroxylase mRNA expression in
      the substantia nigra.

PMID- 8884381
TI  - Postnatal development of glycosidases and gangliosides in the rat central nervous
      system.
AB  - The developmental profiles of sialidase, beta-galactosidase, beta-hexosaminidase
      and beta-glucosidase were compared to those of the gangliosides in rat brain and
      spinal cord. The glycosidase activities (enzyme units/g wet tissue), except beta
      galactosidases, were found to be higher in brain than spinal cord, in adult rats.
      Among the hydrolases, beta-hexosaminidase showed a higher level of activity in
      both brain and spinal cord. In brain, the hydrolases, except beta-glucosidase,
      followed a similar developmental pattern, showing an increase from birth to 21
      days, and then decreased to adult values by day 90. In the spinal cord,
      sialidase, beta-galactosidase, pH 3.1, and beta-hexosaminidase activities
      increased from birth to 21 days, reaching peak values. These activities then
      declined to adult values by 90 days of age. However, beta-galactosidase, pH 4.5,
      and beta-glucosidase activities showed a peak at day 14. Brain total ganglioside
      concentration (microgram N-acetylneuraminic acid/g tissue) increased slowly
      between birth and 7 days of age, followed by a rapid phase of increase to attain
      a peak value by day 21. The concentration of total gangliosides in the spinal
      cord is less when compared to the brain. The proportions of individual
      gangliosides in the central nervous system also vaired during development. The
      rapid phase of increase in enzyme activities between 0-7 and 14-21 days and a
      decrease thereafter is consistent with the turnover rate of gangliosides, which
      in rat brain is reported to be highest between 10 and 20 days.

PMID- 8884382
TI  - In vitro induction of radial-like cells by leptomeningeal and cortical astroglial
      conditioned media. Effect of protease inhibitors.
AB  - A population of subcultured astroglia from rat fetal cortex was transformed into
      radial-like cells after exposure to cerebral cortex astroglial conditioned medium
      in vitro. Such changes were also induced by basal medium modified by fetal
      leptomeningeal subcultures, but not by postnatal leptomeninges nor by fetal skin
      fibroblasts. The radializing effects of astroglial conditioned medium were
      inhibited by previous heat treatment. The addition of protease inhibitors to the
      basal medium did not cause spontaneous radialization of subcultured cortical
      astroglia, but increased the length of cell processes and incidence of radial
      like forms when added to cortical astroglial conditioned medium. It is concluded
      that cortical astroglia and leptomeningeal cells share the capability of
      synthesizing and releasing diffusible molecules into the culture medium which act
      as morphogenetic inducers in vitro. Based on the present results, it is suggested
      that such effects would depend on the presence of instructive factor(s) in the
      conditioned medium which are able to induce rearrangement of the cytoskeleton,
      rather than on secreted molecules able to modify cell adhesion to the substrate.

PMID- 8884383
TI  - Regional differences in in vitro growth of neural cell processes during
      development.
AB  - Primary cell cultures from cerebral cortex, striatum and ventral mesencephalon
      obtained from rat fetal (embryonic day 17, E17) or postnatal (day 2, PN2) donors
      were grown either in media conditioned by subcultured astroglia from the same
      regions, an artificial trophic medium, normal human amniotic fluid, or in normal
      human cerebrospinal fluid. To estimate the presence of neuronal-like and non
      neuronal cells, cell morphology and immunocytochemistry against microtubule
      associated proteins and beta-tubulin were taken into consideration. The
      percentage of emitting neural cells and length of cell processes were determined
      after 24 hr in culture. Growth of cell processes in neuronal and non-neuronal
      cells from prenatal striatum was minimal compared with that in cerebral cortex
      and ventral mesencephalon, regardless of the culture condition. Nerve growth
      factor, basic fibroblast growth factor or epidermal growth factor did not
      significantly modify cell growth in E17 cultures, except for epidermal growth
      factor, which reduced the number of emitting cells in striatal cultures and
      increased it in cerebral cortex ones. Cultures derived from postnatal striatum
      showed a significant increase in neurite length when grown in an astroglial
      conditioned medium as compared to cultures derived from prenatal (E17) striatum.
      Results suggest significant regional differences in the brain regarding growth of
      cell processes at age E17, and reversal of striatal ability to grow cell
      processes by postnatal day 2. Reduced growth of cell processes showed by E17
      striatum cultures was rather independent of the culture media. This fact could
      suggest that such early regional differences would depend on characteristics of
      sublineages present at this developmental stage, which would modulate the
      organization of regional neuropils. The restricted growth of cell processes in
      cultures from E17 striatum, no longer present in postnatal striatum, suggests
      that inputs to the striatum may modify expression of cell lineages at later
      stages of development.

PMID- 8884384
TI  - Development of vestibular function: biochemical, morphological and
      electronystagmographical assessment in the rat.
AB  - Glutamate decarboxylase and choline acetyltransferase were measured in
      homogenated ampullar cristae of rats during development from postnatal day 13 to
      60 to determine changes in levels of these enzymes during early postnatal
      development. Afferent and efferent innervation of the hair cells of the
      developing cristae were studied using electron microscopy. In parallel, groups of
      rats, postrotatory nystagmus were used to assess the development of semicircular
      canal function during the same time interval. The level of glutamate
      decarboxylase was high on postnatal day 15 and did not change notably over the
      remaining days to day 60. Activity of choline acetyltransferase was nearly absent
      at day 15, but reached levels seen in mature animals by day 17, and remained
      almost unchanged thereafter. In contrast, as revealed by electronmicroscopy,
      afferent and efferent innervation appeared to be mature by day 8. Postrotatory
      nystagmus presented the adult-like features from day 19 onward. According to
      these results, a role for glutamate decarboxylase in afferent transmission is
      suggested by the parallel development of levels of glutamate decarboxylase and
      afferent innervation of the ampullary cristae. The finding of a similar time
      course of development of choline acetyltransferase levels and postrotatory
      nystagmus suggests that a cholinergic efferent innervation is involved in the
      onset of vestibular-ocular function.

PMID- 8884385
TI  - Development of vestibular and auditory function: effects of hypothyroidism and
      thyroxine replacement therapy on nystagmus and auditory evoked potentials in the
      pigmented rat.
AB  - The functional development of semicircular canals and some brainstem structures
      of the auditory system was followed in parallel with time in control and
      propylthiouracyl-induced hypothyroid pigmented rats by respective recording of
      postrotatory nystagmus response and auditory evoked brainstem potentials, with
      the aim of discovering the timing of permanent alterations of these responses in
      congenital hypothyroidism. A group of hypothyroid rats which under went thyroxine
      replacement therapy from postnatal day 12 onward was also included in our studies
      to corroborate the involvement of thyroid hormones in these effects. Postrotatory
      nystagmus and auditory evoked responses were absent in congenital hypothyroid
      rats. In the thyroxine-replaced group postrotatory nystagmus values showed no
      differences from the control group from postnatal day 28 onward. Auditory evoked
      potentials in thyroxine-replaced animals could not be elicited at 30 dB, but by
      increasing the intensity of stimulus to 70 dB, values of latencies of the four
      waves composing the response were indistinguishable from controls from postnatal
      day 39 and thereafter. These results show that hypothyroidism affects both
      semicircular canal and auditory function, the latter more severely than the
      former, but that these effects can be prevented when thyroxine replacement
      treatment is started in early stages of postnatal development.

PMID- 8884386
TI  - Stimulation of glutamine synthetase activity by excitatory amino acids in
      astrocyte cultures derived from aged mouse cerebral hemispheres may be associated
      with non-N-methyl-D-aspartate receptor activation.
AB  - We have been using glial cells derived from aged mouse cerebral hemispheres
      (MACH) at several passages to study the responsiveness of astrocytes to
      microenvironmental signals in culture. In the present study, we examined the
      effects of excitatory amino acids on the activity of glutamine synthetase, a
      marker for astrocytes. MACH glia cell passages 25 to 29 were used. Culture groups
      were Dulbecco's modified Eagle's medium +10% fetal bovine serum (control);
      glutamate 100 microM; gamma-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid
      (AMPA) 50 microM; kainic acid 10 microM; N-methyl-D-aspartate (NMDA) 10 microM.
      In all treated groups glutamine synthetase activity was significantly higher than
      in controls. We speculate that this increase represents an enhanced
      differentiation of immature astrocytes. In a second series, we examined the
      effects of glutamate receptor antagonists on glutamine synthetase activity as
      follows. MACH cultures were treated with glutamate 100 microM in combinations
      with either L(+)-2-amino-3-phosphonopropionic acid (L-AP3; 50 microM); D(-)-2
      amino-5-phosphonopentanoic acid (D-AP5; 50 microM) or 6,7-dinitroquinoxaline-2,3
      dione (DNQX, 50 microM). The increase in GS activity produced by glutamate was
      inhibited by the non-selective NMDA receptor antagonist, DNQX, but not by the
      metabotropic receptor antagonist, L-AP3 or a selective NMDA receptor antagonist,
      D-AP5. We also found that in cultures treated with glutamate, a number of
      astrocytes resembled "reactive astrocytes" morphologically. These astrocytes were
      absent in cultures treated with glutamate+DNQX. The findings provide supportive
      evidence that astrocytes from aged mouse cerebral hemispheres respond to
      excitatory amino acids and that this response is mediated by non-NMDA receptor
      activation.

PMID- 8884387
TI  - Human fetal brain cells in aggregate culture: a model system to study regulatory
      processes of the developing human neuropeptide Y (NPY)-producing neuron.
AB  - Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the brain and
      it has been implicated in a wide range of brain functions, including mentation.
      The aim of this study was to establish a culture system of human fetal brain
      cells expressing NPY in a regulated manner. The NPY production in response to
      forskolin and phorbol 12-myristate 13-acetate (PMA) was taken as a criterion for
      regulated expression of NPY. Aggregates were formed from dissociated cells
      derived from the cerebral hemispheres of human fetuses (12.5-19 weeks' gestation)
      by constant rotation and were maintained in serum-free medium. A 24 hr exposure
      to 10 microM forskolin + 20 nM PMA led to a 2-6-fold increase in NPY content of
      the cultures, most of which (80-90%) was secreted into the medium. The latter
      consisted of two substances differing in size: one corresponding in size to
      proNPY and the other to NPY. Thus, forskolin + PMA led to an increased production
      of NPY. Exposure to PMA alone led to an increase in NPY production comparable to
      that seen after forskolin + PMA and this effect of PMA was dose-dependent. In
      contrast, forskolin alone did not induce NPY production. Conditioned medium,
      derived from monolayer cultures enriched with human astrocytes, enhanced NPY
      production in response to forskolin+PMA in an age-dependent manner. The NPY
      production by aggregates derived from a 12.5 week-, 14-week- and 18-week-old
      fetus was enhanced 3-3.6-fold, 1.6-2-fold and 1.1-fold, respectively. Thus,
      expression of the NPY neurons in this culture system is a regulated process. The
      NPY production is enhanced markedly by activation of the protein kinase C pathway
      and by an astrocyte-derived soluble substance(s). Based on these results, we
      propose that this culture system can serve as a model for the study of regulatory
      processes of the human developing NPY neuron.

PMID- 8884388
TI  - Somatosensory evoked potentials in aphasic patients.
AB  - The purpose of this study was to employ evoked potentials to evaluate the
      function of the somatosensory system in a group of right hemiplegic aphasic
      patients in whom conventional physical examination was inapplicable. Bilateral
      somatosensory evoked potentials (SEPs) in response to stimulation of the median
      nerve were recorded in 20 patients, and unilateral recordings were performed with
      20 healthy, aged, matched controls. The major abnormality, present in 13
      patients, was absence or reduction of the amplitude of the cortical components
      N19 and P22 in the lesioned side of the brain. Consequently, the only significant
      difference between the lesioned versus nonlesioned brain side in patients, and
      between patients and control subjects was in the amplitude of the cortical
      components. Since a strong correlation exists between the detected abnormality
      and impaired somatosensory function, it is concluded that it is highly probable
      that many aphasic patients suffer somatosensory deficits which, being difficult
      to assess, are overlooked by the medical personnel.

PMID- 8884389
TI  - Wave theory of large-scale organization of cortical activity.
AB  - Large neural systems are conveniently analyzed through a continuum model in which
      the differential element contains many cells and consequently near-neighbor
      synaptic connections can be neglected. At this level of detail, the constituent
      neurons can be replaced by figurative cells that are purely excitatory or
      inhibitory. The simplest continuum configuration that approximates the mammalian
      cortex consists of two layers each containing both species of cell, with a time
      delay in the interlayer synapses. If it is variable, the delay acts like a
      control, determining the wavelengths and frequencies of waves that preferentially
      grow out of a small disturbance in neural activity level. The amplified mode
      structure becomes more complex as delay increases and is always characterized by
      wavelengths significantly larger than typical synaptic connection ranges. As the
      favored modes grow and propagate they associate, through simultaneous activation,
      mutually distant continuum elements. The activation patterns are reproducible in
      wavelength spectrum, but, especially at large delays, their spatiotemporal forms
      are partly functions of the initial random noise. Since the individual continuum
      elements contain enough neurons to be capable of storing as much information as
      artificial neural networks, it can be argued that the delay-controlled waves
      provide a mechanism by which "memories" can be reproducibly recalled, and
      "creative thoughts" generated and developed.

PMID- 8884390
TI  - Massage therapy reduces anxiety and enhances EEG pattern of alertness and math
      computations.
AB  - Twenty-six adults were given a chair massage and 24 control group adults were
      asked to relax in the massage chair for 15 minutes, two times per week for five
      weeks. On the first and last days of the study they were monitored for EEG,
      before, during and after the sessions. In addition, before and after the sessions
      they performed math computations, they completed POMS Depression and State
      Anxiety Scales and they provided a saliva sample for cortisol. At the beginning
      of the sessions they completed Life Events, Job Stress and Chronic POMS
      Depression Scales. Group by repeated measures and post hoc analyses revealed the
      following: 1) frontal delta power increased for both groups, suggesting
      relaxation; 2) the massage group showed decreased frontal alpha and beta power
      (suggesting enhanced alertness); while the control group showed increased alpha
      and beta power; 3) the massage group showed increased speed and accuracy on math
      computations while the control group did not change; 4) anxiety levels were lower
      following the massage but not the control sessions, although mood state was less
      depressed following both the massage and control sessions; 5) salivary cortisol
      levels were lower following the massage but not the control sessions but only on
      the first day; and 6) at the end of the 5 week period depression scores were
      lower for both groups but job stress score were lower only for the massage group.

PMID- 8884391
TI  - Transient evoked otoacoustic emissions in nonsurgical ear.
AB  - Several studies have reported contralateral hearing deficits following ear
      surgery. This study aimed to evaluate changes in micromechanical cochlear
      properties which could occur in the contralateral ear following ear surgery,
      using transient evoked otoacoustic emission (TEOAE) recording. Surgery involved
      tympanic membrane surgery in 13 cases and middle ear surgery in 16 cases. TEOAEs
      were recorded and compared for contralateral ears before (day 1: D1) and after
      (day 2: D2) ear surgery. Two patients failed to show a TEOAE reproductibility >
      75%, and were excluded from the study, thus reducing the number of patients to
      27. Results were compared to those of a control group of 12 normal hearing
      subjects, recorded in similar conditions also on day one (D1) and day two (D2).
      The difference between D1 and D2 was not significant in either group.
      Pre/postsurgery variations in TEOAE amplitude for the patient group were
      negatively and significantly correlated with the corresponding preoperative
      levels in that the greater the presurgical TEOAE level, the larger the decrease
      in postoperative level. Compared to the variation confidence intervals in the
      control group, TEOAE amplitude remained stable in 15 patients, increased in four
      and decreased in eight. These three groups of patients differed only regarding
      preoperative TEOAE amplitude values, which were significantly greater in the
      group which presented a decrease in TEOAE amplitude than in the others. Increase
      in TEOAE amplitude was more frequent after tympanic membrane surgery. On the
      other hand, TEOAE amplitude decrease was more frequent after middle ear surgery,
      and is significant compared to the tympanic membrane surgery results. The results
      show that cochlear micromechanical properties may be reduced in the ear
      contralateral to surgery and that this decrease depends on the severity of the
      surgical procedures in the operated ear, such as drilling or opening of the oval
      window.

PMID- 8884392
TI  - Morphological asymmetries of motoneurons innervating upper extremities: clues to
      the anatomical foundations of handedness?
AB  - Handedness is one of the main issues in laterality research and is known to be
      related to a large number of morphological asymmetries of the central nervous
      system. However, the main focus of previous studies were cerebral structures,
      which ignored the spinal cord as the most distal neural entity innervating the
      muscles of the extremities. We analyzed morphometrically motoneurons from
      segments innervating the arms and hands and compared them with motoneurons of
      segments that innervated the upper trunk. We found an asymmetry with larger
      motoneuron perikaryas on the right side of the spinal cord in segments
      innervating the upper limbs. To our knowledge this is the first time a
      morphological asymmetry on single-cell-level was shown in the spinal cord of man.
      The possible relation of this cellular asymmetry to the origins of handedness is
      discussed.

PMID- 8884393
TI  - Peripheral cuing of covert spatial attention before and after emotional
      conditioning of the cue.
AB  - Spatial cuing of attentional shifts were investigated before and after the visual
      cue had acquired emotional significance through a classical conditioning
      procedure. The study consisted of three phases; an attention preconditioning
      phase, the conditioning phase and an attention postconditioning (extinction)
      phase. In the attention phases, subjects participated in a trial-by-trial cuing
      task, in which the location of the target was validly or invalidly cued by either
      a frame-lit or a completely lit rectangle. During conditioning half the subjects
      (Conditioning group) had a 90 dB white noise unconditioned stimulus (UCS)
      presented together with one of the two attentional cues. This cue was, thus,
      turned into a conditioned stimulus (CS+), while the other cue became a CS-. The
      Control group received the noise uncontingent upon presentations of these
      stimuli. The Conditioning group showed greater skin conductance responses (SCRs)
      to the CS+ compared to the CS-, reflecting that a conditioned response was
      established. When the CS+ served as attentional cue, there was no difference in
      RTs between validly and invalidly cued targets, while responses to invalidly cued
      targets were delayed on all other trials. This suggests that the CS+ reduced the
      cognitive cost of shifting attention from the cued to the uncued location.

PMID- 8884394
TI  - Cholecystokinin octapeptide reverses the inhibitory effect induced by
      electroacupuncture on C-fiber evoked discharges.
AB  - Extracellular single unit recordings were made from spinal dorsal horn wide
      dynamic range neurons in spinal transected, urethane-anesthetized rats. The unit
      discharges elicited by noxious electrical stimulation of the hind paw were
      suppressed by electroacupuncture (15 Hz, 0.3 ms, 3 mA, 30 min) placed at the hind
      leg points (S-36 and SP-6). Local spinal superfusion with naloxone (20
      micrograms/15 microliters) or CCK-8 (10 ng/15 microliters) attenuated, whereas
      CCK-B receptor antagonist L365,260 (2.5 micrograms/15 microliters) enhanced the
      electroacupuncture effect. These findings provide further evidence for the notion
      that CCK-8, in the spinal cord, functions as an antiopioid substrate that
      antagonizes opioid- or electroacupuncture-induced analgesia.

PMID- 8884395
TI  - Essential fatty acid preparation reduces cholesterol and fatty acids in rat
      cortex.
AB  - Previous studies have shown that chronic administration of SR-3 (a 1:4 mixture of
      alpha-linolenic and linoleic acid) affects spatial learning, thermoregulation,
      pain threshold, and protection from seizures. The mode of action of SR-3 is
      unknown. One possible explanation is that SR-3 induces changes in the FA profile
      and in the cholesterol level in neuronal membranes. This study used 10
      independent groups of rats (ni = 12) given 4 weeks of either saline, mineral oil
      (vehicle), alpha-tocopherol (antioxidant), alpha-linolenic acid, linoleic acid,
      or one of 5 different ratios of alpha-linolenic acid:linoleic acid (1:3, 1:4,
      1:5, 1:6, 1:7) as free fatty acids. FA profile and cholesterol level were
      examined by GC method in synaptosomes obtained from the frontal cortex of the
      rats. The mineral oil treated group served as the control group. No difference
      was found in the FA profile or cholesterol level except for the SR-3 treated
      group. The ratio of 1:4 was found to have a significant influence on decreasing
      the cholesterol level and in inducing major changes in the FA profile, such as an
      increase in EFA. These effects of SR-3 may result in modification of the membrane
      fluidity, which may, in turn, enhance cognitive and neuropharmacological effects.

PMID- 8884396
TI  - The long-term impact of treatment with electromagnetic fields on visual memory in
      Parkinson's disease.

PMID- 8884397
TI  - Brain samples from Alzheimer's patients have elevated levels of loosely bound
      iron.
AB  - The amount of loosely bound iron was measured in frontal cortex and cerebellum
      from autopsy brain samples from Alzheimer's patients and from non-demented, age
      matched controls. It was found that the amount of total iron and of ferric iron
      in Alzheimer's brain tissues was significantly higher compared to control samples
      in both regions studied. Neither the ferrous nor the ferrous to ferric ratio were
      found to be changed. Since it is the loosely bound iron that is responsible for
      free radical reactions in vivo, these results are consistent with an increased
      free radical burden in Alzheimer's disease that leads to the progressive
      neurodegeneration seen in this disorder.

PMID- 8884398
TI  - Enhancement of limbic seizures by nocturnal application of experimental magnetic
      fields that simulate the magnitude and morphology of increases in geomagnetic
      activity.
AB  - Over a 200 day period, chronic (limbic) epileptic rats were exposed
      intermittently, for either one or three nights (00 to 08 hr), once very
      approximately 10 days to experimental magnetic fields whose morphology
      (incremental changes in intensity over time) simulated geomagnetic activity. One
      of two intensities and two ripple frequencies (7 Hz, 45 Hz) was employed. The
      display of over seizures following synchronized food presentation significantly
      increased by a factor 3.1 relative to controls when the fields had been activated
      for one or two but not three successive nights. The combined effects of the
      experimental field and ambient geomagnetic activity (> 40 nT) explained
      approximately 12 to 15% of the variance in the daily incidence of seizures.
      Implications for the transient disinhibition of electrical lability within the
      limbic system following suppression of nocturnal melatonin are discussed.

PMID- 8884399
TI  - Behavioral and adaptive status in an experimental model of Alzheimer's disease in
      rats.
AB  - Ten days after bilateral electrolytic lesions of nucleus basalis magnocellularis
      (NBM) we tested behavioral (spontaneous motor activity, acquisition and
      performance of two-way active avoidance, fear-response in open field test, foot
      shock induced aggression, depression-response in learned helplessness test) and
      adaptive status (body temperature at standard, hot and cold environment as well
      as cold restraint-induced gastric lesions) in adult male Wistar rats. Compared to
      intact control and sham-operated rats, the bilateral NBM-lesioned rats showed the
      significant impairment of learning behavior and reduced fear, aggression and
      depression as well as altered body temperature at standard and stressed
      conditions. Namely, it was established that body temperature in NBM-lesioned rats
      was significantly lower at standard laboratory conditions, but in these rats body
      temperature significantly was raised after exposing to cold and hot environment.
      On the other hand, spontaneous motor activity and number and length of cold
      restraint-induced gastric lesions (erosions and petechiae) in NBM-lesioned rats
      were similarly to those in both controls. It could be concluded that NBM plays a
      significant role in cognitive, emotional and adaptive processes in the rats.

PMID- 8884400
TI  - A double-blind, placebo-controlled, crossover, study to evaluate the efficacy of
      subcutaneous sumatriptan in the treatment of atypical facial pain.
AB  - A double-blind, placebo-controlled crossover study was undertaken to assess the
      efficacy and tolerability of sumatriptan in patients with atypical facial pain.
      Patients were aged 18-65 years and had at least a 6 months history of atypical
      facial pain. A total of 19 patients were recruited and assessed for pain scores
      (total, sensory and affective) by using a short form McGill pain questionnaire
      preinjection and and at 60 and 120 minutes after subcutaneous injection of
      sumatriptan (6 mg) or placebo. Safety and tolerability was assessed by recording
      adverse events during and after the injection. One patient received only one
      treatment since her pain symptoms resolved after the first treatment. Rest of the
      patients returned to the clinic 3-6 weeks later and received alternate treatment
      for atypical facial pain in the same fashion as on the first occasion. Treatment
      of patients with sumatriptan produced significant relief in sensory, affective
      and total pain at 120 minutes postinjection (P < .05). Sumatriptan failed to
      produce a significant reduction in sensory and total pain scores at 60 minutes
      following treatment, however the result was statistically significant for the
      affective pain score (P < .05). No death or other serious adverse events were
      reported. No patient was withdrawn from the study due to an adverse event.
      However, all the patients treated with sumatriptan experienced one or more
      adverse events. The most common reported adverse symptoms during the sumatriptan
      treatment period were injection site reactions, headache, feeling of heaviness,
      warm or hot sensation and disorders of mouth or tongue. However, most of these
      side effects were mild and transient. In conclusion, this study points towards
      some beneficial effect of a single subcutaneous injection of sumatriptan in the
      treatment of atypical facial pain. However, this data is not sufficient to
      suggest the clinical utility of subcutaneous sumatriptan (6 mg) for the
      management of atypical facial pain. Further studies are necessary to test the
      effects of prolonged subcutaneous and oral multiple dose administration of
      sumatriptan for the treatment of atypical facial pain.

PMID- 8884401
TI  - Study of labyrinthine function in children using the caloric test: our results.
AB  - We studied caloric responses in a group of 42 healthy children aged between 4 and
      14 years and compared the results with those obtained with the same method and
      equipment in a control group of 57 healthy adults at the Methodist Hospital
      Electronystagmography Laboratory at Houston (Texas). The average response in
      children appeared to be rather low. The confidence regions for unilateral
      weakness (UW) and directional preponderance (DP) measures were much wider in
      children than in adults. The confidence limit for bilateral weakness (BW) was
      lower in the children. The confidence limit for the fixation index (FI) in the
      children, however, was close to that in adults.

PMID- 8884402
TI  - Hearing levels of young patients 10 years after mastoidectomy.
AB  - In several reports, the functional results of mastoid surgery in children have
      been stated to be disappointing. In this study, a series of 49 child patients who
      underwent mastoid surgery for chronic suppurative otitis media were examined 10
      years postoperatively. At surgery, a cholesteatoma was detected in 49% of the
      patients. During the observation period, 33% of the patients were subjected to a
      second operation. At the last follow-up examination, 57% of the operated ears
      showed hearing levels of 20 dB or better, but in 16% hearing levels were worse
      than 40 dB. In 16% of the patients, contralateral disease had required surgical
      treatment and in only 39% of the patients, contralateral ear was found to be
      normal in otoscopy. Still, at the last follow-up examination, 90% of the better
      hearing ears had hearing levels of 20 dB or better and only one patient had
      hearing levels worse than 30 dB in both ears. Compared with an age-and sex
      matched control group, hearing levels of the patients were significantly worse
      but the difference in the mean hearing levels of the better hearing ears was as
      little as 5 dB. Thus, 10 years after mastoidectomy, hearing levels of child
      patients were found to be better than expected.

PMID- 8884403
TI  - Linguistic interaction: the active role of parents in speech therapy for cleft
      palate patients.
AB  - As speech and language intervention becomes more naturalistic, it seems obvious
      that language and other developmental competencies are, in a strong way, a
      function of the quality and quantity of relationships in which the child evolves.
      This paper compares two different speech therapy groups of cleft palate children.
      Children included in the first group received therapy alone with the speech
      pathologist, whereas children from the second group received speech therapy
      accompanied by their mothers. The purpose was to evaluate and provide the mothers
      with interaction modes for facilitating communication. Both groups were evaluated
      before and after the therapy period in order to measure the advance of each
      group. The patients accompanied by their mothers showed a significantly higher
      linguistic advance as compared to patients receiving therapy without their
      mothers. The results in this study support the statement that linguistic
      development in the cleft palate child is strongly related to adult-child mode of
      interaction.

PMID- 8884404
TI  - Prevalence of otitis media, hearing impairment and cerumen impaction among school
      children in rural and urban Dar es Salaam, Tanzania.
AB  - Eight hundred and two (802) primary school children in rural and urban Dar es
      Salaam, Tanzania, were examined to determine the prevalence of otitis media,
      hearing impairment and cerumen impaction by otoscopy and pure tone audiometry.
      Ear disease was found in 222 (27.7%) of the children. One hundred and twenty six
      (15.7%) had cerumen impaction, 70 (8.7%) had sensorineural hearing loss and 21
      (2.6%) had chronic suppurative otitis media. Cerumen impaction was found in
      20.45% of the rural school children and in 14.8% of the urban school children.
      This difference in prevalence between the two groups was not statistically
      significant. The prevalence of chronic suppurative otitis media (COM) was 9.44%
      among the rural school children and 1.3% among the urban school children, the
      difference being statistically significant (P < 0.001). Sensorineural hearing
      impairment was found in 14.1% of the rural school children and in 7.7% of the
      urban children, this also being statistically significant (P < 0.05). The low
      prevalence of chronic suppurative otitis media among the urban school children is
      ascribed to better medical services which facilitate early diagnosis and
      treatment of acute otitis media. This emphasizes the need to improve the health
      services in the rural areas so that acute otitis media is diagnosed and treated
      at the primary level of health care. This will in turn prevent hearing impairment
      due to chronic suppurative otitis media.

PMID- 8884405
TI  - Post-tonsillectomy hemorrhage: an assessment of risk factors.
AB  - Hemorrhage is the most frequent complication of tonsillectomy and is responsible
      for the majority of post-tonsillectomy fatalities. The incidence of this
      hemorrhage has been reported to be as high as 20% [6]. Despite continued efforts
      to reduce this problem, it remains a persistent risk. The charts of 1138 patients
      who underwent tonsillectomy with or without adenoidectomy from 7-1-89 to 6-30-93
      were reviewed. Post-tonsillectomy hemorrhage occurred in 36 patients (3%).
      Preoperative, intraoperative and postoperative risk factors were assessed.
      Postoperative bleeding occurred more often in older patients (69% over age 11
      years). Seventy-five per cent of these patients were operated on for chronic
      tonsillitis as compared to 11% operated on for upper airway obstruction. The
      majority of these patients presented after postoperative day 1 (83%). Four
      patients required blood transfusions. Postoperative hemorrhage occurred in 14% of
      patients with elevated postoperative mean arterial pressures. Intraoperative
      blood loss that exceeded 50 cm3 was also a significant risk factor for post
      tonsillectomy hemorrhage. It is concluded that older age, a history of chronic
      tonsillitis, excessive intraoperative blood loss and elevated postoperative mean
      arterial pressure are significant risk factors for post-tonsillectomy hemorrhage.
      An awareness of these risk factors can help identify patients with potential to
      bleed postoperatively.

PMID- 8884406
TI  - Esthesioneuroblastoma in the pediatric age-group: the role of chemotherapy and
      autologous bone marrow transplantation.
AB  - Esthesioneuroblastoma, a malignant neoplasm arising from olfactory epithelium, is
      unusual in the pediatric age-group. Management has traditionally involved surgery
      and radiotherapy, alone or in combination, with chemotherapy reserved for
      recurrent or high grade disease. We report a single institution experience
      utilizing chemotherapy and radiotherapy as the initial treatment and successful
      control of the primary tumor in two patients. In one patient, neck dissection and
      high dose chemotherapy combined with autologous bone marrow transplantation were
      used as successful salvage therapy of neck metastasis. Both patients are alive
      and disease free with a mean follow-up of 56 months. These results support the
      role of chemotherapy in the treatment of esthesioneuroblastoma and suggest that
      chemotherapy be used as part of the initial combined modality treatment plan.

PMID- 8884407
TI  - Pediatric brain stem gliomas with the predominant symptom of sleep apnea.
AB  - Two children complaining of sleep apnea presented with brain stem gliomas. In the
      early stage of their illness, neurological disorders were too subtle to be
      recognized as significant by the physicians or to be noted by the parents. Case 1
      experienced an episode of unsteady gait and weakness in the bilateral arms, at
      the age of 5. When it recurred after 7 years of remission, the predominant
      symptom was sleep apnea. Case 2 exhibited nasality of speech as the earliest sign
      of this illness very early in his life, presumably 5 years before the diagnosis
      of brain stem glioma. A slight sleep apnea which developed afterwards did not
      draw attention of the physicians because no neurological signs other than
      paralyses of the bilateral soft palates were present. MRIs of the both cases
      revealed diffuse, infiltrating lesions in the pons, the medulla oblongata and the
      upper cervical spinal cord. Both cases shared some features: (1) diagnostic delay
      of several years from the first symptom; (2) the main lesion in the medulla
      oblongata, where important structures for respiratory control are identified; (3)
      infiltrative growth patterns in the MRI of the tumor, which might account for the
      uncommon clinical courses.

PMID- 8884408
TI  - Correlation of clinical sinusitis signs and symptoms to imaging findings in
      pediatric patients.
AB  - The purpose of this study was to determine the correlation between signs and
      symptoms of upper respiratory tract disease and sinus images in a convenience
      sample of sixty pediatric patients scheduled for computed tomography or magnetic
      resonance imaging of the head for non-sinus diagnoses over a 2-year period. The
      study was carried out in a tertiary pediatric referral center. Each patient
      underwent rhinoscopy and otoscopy just prior to imaging, and each patient's
      parent was asked to fill out a questionnaire regarding recent symptoms of upper
      respiratory tract infection; a blinded comparison was then made between
      respiratory signs and symptoms and images of the paranasal sinuses. Forty-seven
      percent of patients had abnormalities of their sinus images, and a significant (P
      < 0.05) correlation was found between the presence of absence of respiratory
      signs and symptoms and the presence or absence of abnormalities of sinus images,
      especially in younger patients. In conclusion, a large percentage of pediatric
      patients undergoing imaging procedures of the head for non-sinus diagnoses have
      sinus image abnormalities. In the population studied these imaging abnormalities
      appear to reflect ongoing or resolving upper respiratory tract viral or allergic
      inflammation.

PMID- 8884409
TI  - 'Hemostatic pause' in pediatric tonsillectomy?
AB  - A randomized prospective study was performed on 101 children undergoing
      dissection tonsillectomy in two different sequences. In the 'pause' sequence, a
      period of inactivity lasting 1.5 min ('hemostatic pause') with the Boyle-Davis
      gag relaxed and the fossae packed with gauze swabs was implemented after the
      tonsils were excised. Hemorrhage was controlled exclusively by ligatures. The
      duration of tonsillectomy and the number of ligatures used were accurately
      recorded. The procedure was identical in the 'no pause' group but the pause
      period was omitted. No reactionary haemorrhage occurred. There was no significant
      difference in the operating time between the two groups, but the mean number of
      ligatures required was significantly reduced in the 'pause' sequence. We conclude
      that 'hemostatic pause' in tonsillectomy reduces the amount of ligatures needed
      for satisfactory hemostasis.

PMID- 8884410
TI  - Ataxia telangiectasia and mucoepidermoid carcinoma of the parotid gland: a case
      report.
AB  - Ataxia telangiectasia (AT) is an immunodeficiency disorder with increased
      incidence of malignancy. Most of the tumors are lymphomas, and salivary gland
      neoplasms are very uncommon. A case with ataxia telangiectasia and mucoepidermoid
      carcinoma of the parotid gland, the second case in English literature, was
      presented. The treatment was discussed under the view of the literature.

PMID- 8884411
TI  - Child's tuberculous lymphadenitis with fistula evoked by the BCG stem.
AB  - Lymphadenitis with persisting fistualas in children is almost always conditioned
      by specific inflammation, tuberculosis, zoonoses, actinomycoses. Tuberculosis of
      the lymph nodes can either be primary or post-primary. In this case report we
      have dealt with a case of a rare primary lymph node tuberculosis that arose as a
      result of vaccination complications. Disturbance of cellular immunity was the
      reason for BCG lymphadenitis. In references, the reasons for BCG-itis as well as
      vaccination contra-indications have been described.

PMID- 8884412
TI  - DNA damage after exhaustive treadmill running in trained and untrained men.
AB  - The single cell gel electrophoresis (SCG) assay was used to compare the
      occurrence of DNA damage in peripheral white blood cells in 6 trained (TR) and 5
      untrained (UT) men after exhaustive exercise. The subjects completed an
      incremental treadmill test until exhaustion (maximal lactate: 12.9 +/- 1.7 in TR
      and 12.2 +/- 2.5 mmol.l-1 in UT). A clear and significant increase of DNA
      migration from 2.31 +/- 0.20 (TR) and 2.22 +/- 0.16 (UT) at rest to 2.65 +/- 0.30
      (TR) and 3.00 +/- 0.41 tail moment (UT) was found 24 hours after exercise.
      Noteworthy is that the increase of DNA migration was significantly lower in TR (+
      18.7 +/- 6.8%) compared to UT (+ 35.7 +/- 8.9%). Plasma levels of malondialdehyde
      (MDA) were not significantly increased in TR and UT after exercise. At rest and
      15 minutes after exercise MDA-values were significantly lower in TR compared to
      UT. In conclusion the present investigation demonstrates the occurrence of DNA
      damage in white blood cells following exhaustive exercise. This observation may
      be induced by oxidative stress. Our data suggest that adaptation to training
      seems to be capable of reducing free radical associated effects, such as DNA
      damage. Further investigations are needed to clarify the causal mechanisms and
      biological relevance of exercise-induced DNA damage.

PMID- 8884413
TI  - Influence of sleep and meal schedules on performance peaks in competitive
      sprinters.
AB  - The influence of sleep and meal schedules on performance in short distance
      running was assessed in a group of 8 national-class competition male sprinters.
      They were tested on Saturdays for five consecutive weeks. On each testing day,
      the performance time for an 80 m sprint was registered on eight different
      occasions during days 1 and 4, on 9 occasions on days 2 and 5, and on 7 occasions
      on day 3. On control days (days 1 and 4) performance gradually improved during
      the morning up to 13:00 h, decreased at 15:00 h, and again improved thereafter,
      with a maximum peak performance at 19:00 h. On day 2, in which sleep/wake cycles
      and meal-times were advanced for two hours, and on day 3, in which timetables
      were delayed for two hours, maximum peak performance was observed at 17:00 h and
      21:00 h, respectively. At the time of maximum peak performance on both days a
      statistically significant improvement was observed as compared with the control
      day (day 2, p < 0.01; day 3, p = 0.001). On day 5, in which only the sleep/wake
      cycle was advanced for two hours, performance in the afternoon and evening was
      similar to that recorded on days 1 and 4. We observed that easy manipulation of
      sleep and meal schedules would allow competitive sprinters to synchronize peak
      power output with the time of the athletic event, increasing the chances for
      improvement in performance.

PMID- 8884414
TI  - Fatigue effects on muscle excitability.
AB  - Repeated isometric or shortening contractions of skeletal muscle cause muscle
      fatigue but several prior studies have reported an apparent absence of muscle
      fatigue when humans performed up to 70 lengthening contractions. We pursued the
      hypothesis that perhaps muscle excitability is a factor that aids force
      preservation with repeated eccentric actions. Soleus compound muscle action
      potential (M-wave) latency, peak-to-peak amplitude (PPA), duration, and area
      under the curve were examined in 12 subjects (mean age 24.3 y) over 4 testing
      days that included: no exercise, isometric exercise (neutral ankle angle),
      isokinetic (0.5 rad.s-1) concentric and eccentric exercise of the plantar flexors
      in the seated position on a Biodex dynamometer. Supramaximal shocks were
      delivered to the tibial nerve in the popliteal fossa at baseline (3 shocks, 1 min
      apart), during exercise (1 shock-after each of 5 bouts/10 contractions), and
      during 10-min recovery. From initial to final contractions, concentric,
      isometric, and eccentric fatigue was -32, -41 and + 2% (Condition by Trial
      Interaction, F2,22 = 25.1, p = 0.000). No changes occurred in latency or duration
      (p > 0.05), but PPA (Condition by Time interaction, F51,561 = 3.7, p = 0.000)
      increased during isometric and eccentric exercise and remained elevated during
      recovery. Area increased (F51,561 = 3.1, p = 0.000) significantly during all
      three exercise conditions and approximated baseline by minute 8 of recovery. It
      was concluded that although the potentiation of the action potential of
      individual muscle fibers seems to be the common mechanism underlying the increase
      in muscle excitability during plantar flexion exercise, it is possible that
      different factors could cause such a non-specific response.

PMID- 8884415
TI  - Effect of strength training on blood pressure measured in various conditions in
      sedentary men.
AB  - To examine the effect of long term strength training on heart rate and blood
      pressure, measured in different conditions, and on their variability, thirty
      healthy, previously sedentary men were randomized into a training and a control
      group. The strength training program consisted of 48 training sessions on a
      multigym apparatus at a frequency of 3 sessions each week, involving leg press,
      bench press, leg curl, shoulder press, leg extension and sit ups. The control
      group was asked not to change their sedentary lifestyle. In the subjects of the
      training group the load could be increased significantly for all exercises (p <
      0.01). Heart rate and blood pressure were measured at rest in the supine and
      sitting position, during 24 hours with a non-invasive ambulatory device and
      during an exercise test on a cycloergometer. Repeated measures analysis of
      variance did not show an effect of strength training on heart rate or on blood
      pressure. In addition, power spectral analysis of the RR interval (ECG) and of
      the beat-to-beat blood pressure in the supine subject revealed similar total, low
      frequency and high frequency power before and after training, indicating that the
      neural control of both heart rate and blood pressure was not affected by a 16
      week program of strength training.

PMID- 8884416
TI  - Relationships between testosterone, cortisol and performance in professional
      cyclists.
AB  - In the literature the use of plasma levels of cortisol and the testosterone and
      testosterone: cortisol ratio for training management is encouraged. Decreased
      levels of testosterone and increased levels of cortisol are suggested to be
      indicative for a disturbance in the anabolic-catabolic balance, which may express
      itself in decreased performance. The purpose of the study was to examine if the
      acute hormonal response to a bout of exercise and the resting levels of
      testosterone, luteinizing hormone (LH) and cortisol are correlated to performance
      in cyclists. In addition, the effect of training on this correlation was studied.
      Ten professional cyclists participated and measurements took place before and
      after a defined period of training. Maximum workload (Pmax), determined on a
      cycle-ergometer with a slowly increasing protocol, increased by 30 watt (p <
      0.001). Workload at a lactate level of 4 mmol/l (P4) increased by 18 watt (p <
      0.05). Post training, resting testosterone levels decreased from 28.8 +/- 74
      nmol/l to 24.6 +/- 90 nmol/l (p < 0.05). Resting cortisol levels increased from
      272 +/- 110 nmol/l pre training to 379 +/- 242 nmol/l post training (p < 0.05).
      These results indicate an increased catabolic state. The acute hormonal response
      and the resting levels of LH were not changed post training. The resting levels
      of testosterone and cortisol and the acute response to exercise showed no
      correlation with performance pre and post training. In spite of an increased
      catabolic state post training there was an increase in performance. These results
      suggest that in endurance trained cyclists, decreased testosterone levels,
      increased cortisol levels and a decreased testosterone: cortisol ratio does not
      automatically lead to a decrease in performance or a state of overtraining.

PMID- 8884417
TI  - Body composition, cardiovascular risk factors and liver function in long-term
      androgenic-anabolic steroids using bodybuilders three months after drug
      withdrawal.
AB  - The purpose of this study was to investigate in a cross-sectional design body
      composition, muscle fiber characteristics, cardiovascular risk factors and liver
      enzymes in long-term androgenic-anabolic steroids (AAS) using bodybuilders three
      months after drug withdrawal (AAS group; n = 16) and in non-users (CO group; n =
      12). Training and dietary data were collected in all subjects. Anthropometry
      included weight, height, 8 skinfolds and 11 circumferences. Percentage fat
      (%FAT), fat mass (FM) and lean body mass (LBM) were calculated. In a muscle
      biopsy from the vastus lateralis muscle water content, fiber type distribution
      and diameters of fiber type I and type II were determined. Age, height, training
      characteristics, nutrition, skinfolds, %FAT and FM did not differ between the
      groups. The AAS group had greater BW and LBM, and larger circumferences of
      thorax, waist, upper arm and thigh than the CO group. Muscle biopsy data were
      comparable, except for muscle fiber diameter of type I which was larger in the
      AAS group. No differences in serum values of total cholesterol, HDL-cholesterol
      and triglycerides, nor in systolic and diastolic blood pressure were observed. In
      both groups serum alkaline phosphatase and gamma GT were within the normal range.
      This study suggests that in long term AAS using body-builders, after a three
      months AAS free period, BW is greater than in non drug users. This is reflected
      in larger LBM, circumferences and diameter of muscle fiber type I. In addition,
      no differences in fat mass, blood pressure, lipoprotein profiles and liver
      enzymes exist between AAS users three months after interrupted drug use and their
      non drug using counterparts.

PMID- 8884418
TI  - Doping in cyclism: results of unannounced controls in Flanders (1987-1994).
AB  - Unannounced doping control in cyclism, the most favourite sport in Flanders,
      resulted in 7.8% positive cases in 4374 analysed samples during the period 1987
      1994. Ephedrines, amphetamine and nandrolone were frequently misused and polydrug
      abuse including ephedrines and amphetamine seemed to be very popular. The abuse
      of methamphetamine, methylphenidate and pemoline, formerly favourite drugs in
      cyclists is decreasing while prolintane, codeine and the anabolic steroids
      nandrolone and testosterone were more frequently detected. The misuse of
      forbidden substances by athletes competing in the official Belgian Cyclist
      Federation and in amateur federations was 5.8% and 8.9%, respectively. Several
      cyclists however attempted to circumvent doping control.

PMID- 8884419
TI  - Gender differences in adrenergic regulation of lipid mobilization during
      exercise.
AB  - Gender differences in adrenergic regulation of glycerol levels in subcutaneous,
      abdominal adipose tissue were investigated during submaximal exercise in non
      obese, healthy men and women, using microdialysis. During exercise, glycerol
      levels in venous plasma and venous serum concentrations of free fatty acids
      increased more in women and reached about two-fold higher values than in men (p <
      0.005 or less). Plasma noradrenaline and insulin did not differ between the
      sexes, whereas plasma adrenaline was two-fold higher in men than in women during
      exercise (p < 0.01). The glycerol levels in adipose tissue increased during
      exercise and decreased in the post-exercise period in either sex. When the non
      selective beta adrenoceptor blocking agent propranolol was added to the
      microdialysis perfusate before exercise was initiated, the subsequent increase in
      dialysate glycerol was significantly diminished in both sexes (p < 0.05). A
      similar addition of the alpha adrenoceptor blocking agent phentolamine, however,
      caused a significant further rise in tissue glycerol in men (p < 0.05), whereas
      the exercise induced increase in glycerol levels remained unaffected by
      phentolamine in women. Adipose tissue blood flow did not change during exercise
      in either men or women. In either sex, dialysate lactate levels increased during
      exercise. This increase was not altered if alpha- or beta-blocking agents were
      added to the perfusate. In summary, during short term submaximal work, women have
      a higher increase in circulating lipid than men. This appears, at least in part,
      to be due to a sex difference in the adrenergic regulation of lipid mobilization
      during exercise. In men exercise activates beta- as well as alpha-adrenergic
      receptors in adipose tissue, whereas only beta receptors are activated in adipose
      tissue of women. Finally, methodological investigations indicate that
      microdialysis is a valid method for short-term exercise experiments.

PMID- 8884420
TI  - Postexercise proteinuria in childhood and adolescence.
AB  - Postexercise proteinuria has been observed in healthy adults but there was a need
      for information in young individuals. Boys and girls (n = 170) from 6 to 18 years
      of age were submitted to maximal exercise by the 20-meter shuttle run test. Urine
      collection was made prior to and 30 min after completion of the run. Total
      protein, albumin, beta 2-microglobulin (beta 2-m), retinol-binding protein (RBP)
      and creatinine were determined on each sample. Resting values for total protein,
      albumin, beta 2-m and RBP excretion rates were within the normal range for each
      component with a progressive increase for total protein and albumin. The effect
      of exercise increased with age. Between the 6 and 9 year olds there was a gender
      difference in postexercise proteinuria, boys enhanced the excretion of
      macromolecules while girls did not show any increase by maximal exercise. The
      excretion rates of all protein components were related to the absolute intensity
      of exercise expressed as maximal speed (R between 0.86 and 0.90, p < 0.001). High
      and low-molecular weight protein excretion gave evidence of increasing
      disturbances from the age of 9 to 18 years in boys and girls. These data clearly
      demonstrate that 1) postexercise proteinuria is present at maximal exercise from
      childhood to adolescence; 2) the magnitude of protein excretion is strictly
      related to the absolute intensity of exercise; 3) the glomerulus permeability and
      the tubular reabsorption process are both different in pre- and postpubertal
      children and adolescents.

PMID- 8884421
TI  - Injury rates and physiological changes associated with lateral motion training in
      females.
AB  - The purpose of this investigation was to evaluate physiological changes and
      injury rates associated with lateral motion (slideboard) training. Twenty-five
      females performed slideboard exercise 3 days per week, 1 hour each session, over
      a 10 week period. Eleven females served as controls. The subjects were pre and
      post tested via treadmill exercise to determine VO2peak. Body composition was
      analyzed by a seven-site skinfold equation. The slideboard subjects (SBS) were
      evaluated daily for injury incidence. A factorial repeated measures ANOVA (p <
      0.05) revealed a significant 14% increase in VO2peak. No significant
      modifications were shown for body composition. The incidence of injury was 80%
      for Grade I injuries, 52% for Grade II injuries, 0% for Grade III injuries, and
      4% for Grade IV injuries. Thus, the primary injury reports were of a Grade I and
      Grade II level of severity. The present injuries were largely associated with
      delayed onset muscle soreness (DOMS) in the medial leg musculature during the
      first two weeks of training. These results show that during a 10 wk training
      program lateral motion exercise is an effective mode for improving
      cardiorespiratory fitness. In addition, the risk of incurring an injury requiring
      medical attention appears to be quite low. However, untrained women who perform
      this activity at a frequency, duration, and intensity similar to the present
      study may experience muscle soreness during the initial period of training.

PMID- 8884422
TI  - Unusual development of acute exertional compartment syndrome due to delayed
      diagnosis. A case report.
AB  - Our report describes the case of a 20 year old man who developed an acute
      exertional anterior tibial compartment syndrome after playing soccer for five
      minutes. No trauma was reported. Correct diagnosis was delayed for 18 hours,
      because pain was misinterpreted as resulting from acute muscular tetanic spasm
      induced by hyperventilation. Fasciotomy was contributed. After one year, the
      patient complained of early fatigue. Electromyographically the reinnervation had
      not yet been completed. This case illustrates the necessity for careful
      observation of non-trauma related acute tibial anterior pain appearing even at
      the beginning of strenuous exercise. It is important to recognize the possibility
      of a very acute onset of exertional compartment syndrome that does not subside
      with rest. Only early diagnosis and fasciotomy can prevent severe complications
      of an acute exertional compartment syndrome.

PMID- 8884423
TI  - Psychometric correlates of perception during arm ergometry in males and females.
AB  - This study examined psychometric correlates of rated perceived exertion (RPE) and
      perceived dyspnea (RPD) during progressive arm ergometry. Thirty female and 30
      male subjects completed the State-Trait Anxiety Inventory (STAI), the Profile of
      Mood States Questionnaire (POMS) and the Body Awareness Scale (BAS) followed by
      progressive arm ergometry to exhaustion. Heart rate, minute ventilation, RPD and
      RPE were obtained during the last 30 seconds of every two minute stage of the
      exercise test. The female group had significantly (p < 0.05) higher RPE (overall
      and local), RPD, minute ventilation, and heart rate than did the male group
      during exercise at absolute power outputs of 33, 50 and 67 watts. At each of
      these work loads, both state anxiety and body awareness were positively and
      significantly (p < 0.05) related to RPE and RPD in the male but not in the female
      sample. Repeated measures ANOVAs revealed that a subset of high trait anxious
      males (N = 10) exhibited higher minute ventilatory volumes and dyspnea ratings
      than a subset of low trait anxious males (N = 10). The results show that elevated
      trait anxiety is associated with dyspnea during arm ergometry and that there are
      gender differences in psychological correlates of perception during arm exercise,
      but shed no light on why the gender differences exist.

PMID- 8884424
TI  - State anxiety following 20 minutes of bicycle ergometer exercise at selected
      intensities.
AB  - An attempt was made to determine if state anxiety responses following acute
      exercise are influenced by the intensity of exercise. Fifteen adults (5 female,
      10 male) completed 20 minute sessions of bicycle ergometer exercise on separate
      days at intensities equal to 40, 60, or 70% VO2peak. Expired gas spirometry was
      employed to determine peak oxygen consumption and to control the workload during
      the submaximal protocols. State anxiety (STAI-Y1) was assessed prior to and
      following each exercise session, and 5, 60 and 120 minutes post-exercise.
      Repeated measures ANOVA revealed that state anxiety decreased (p < 0.05)
      following each exercise condition. Post hoc analysis indicated that state anxiety
      was significantly (p < 0.05) reduced at all post-exercise assessments in the 40
      and 60% VO2peak conditions. State anxiety was elevated by 3.4 units at 5 minutes
      following exercise at 70% VO2peak, but decreased (p < 0.05) below baseline at 60
      and 120 minutes post-exercise to a degree not different from the other exercise
      conditions. Further analysis indicated the increase in anxiety 5 minutes
      following 70% VO2peak exercise was significant only in subjects with low baseline
      state anxiety values, whereas it was unchanged in subjects with higher baseline
      values. In conclusion, 20-minute sessions of cycle ergometer exercise at
      intensities ranging from light to heavy were equally effective in reducing state
      anxiety in young, healthy adults. However, this reduction is delayed somewhat
      following exercise at a high intensity (i.e., 70% VO2peak).

PMID- 8884425
TI  - Cellular and molecular analysis of lymphoid development using Rag-deficient mice.
AB  - The establishment of a functional immune system with diverse antigen receptors is
      dependent on the V(D)J recombination activating gene products Rag-1 and Rag-2.
      These two proteins constitute the key lymphoid components required for the
      activation of antigen receptor rearrangement. Both Rag-1 and Rag-2 are required
      for the catalysis of the initial stages of V(D)J recombination. Thus, functional
      disruption of either the Rag-1 or Rag-2 genes by homologous recombination, leads
      to immunodeficiency due to lymphoid arrest at a stage prior to the recombination
      of the antigen receptor loci. In Rag-deficient mice, both B- and T-cell
      differentiation is eliminated due to the absence of antigen receptors. Lymphoid
      development can be restored by the introduction of rearranged antigen receptor
      transgenes that give rise to monoclonal populations of fully mature B- or T
      cells. The absence of the major conventional populations of B- and T-cells from
      the Rag-deficient mice provided an excellent background for studying the
      molecular and cellular mechanisms of lymphoid differentiation. The Rag-deficient
      background has been used as a system for: the functional analysis of Rag-1 and
      Rag-2; studying the developmental functions of antigen receptors and other
      molecules of the immune system; the molecular analysis of the early stages of the
      B- and T-cell lineages; the co-development of lymphocytes with stroma cells; the
      identification of minor subpopulations of the developing immune system; the
      involvement of lymphoid populations in the onset of pathogenesis. In addition,
      the development of the "blastocyst complementation assay" methodology, based on
      the phenotype of the Rag-/- mice, allowed the functional analysis of numerous
      lymphoid specific components.

PMID- 8884426
TI  - Immune deficiency in SCID mice.
AB  - Since the discovery of SCID mice in 1983, numerous studies utilizing these mice
      were carried out. These investigations can be classified into two major groups.
      First, the analysis of the immune defect has revealed defective V(D)J
      recombination and defective DNA double-strand break repair, and has lead to the
      identification of the candidate gene for SCID mice. Second, the use of SCID mice
      to explore ways to introduce a murine or xenogeneic immune system into SCID mice
      by taking advantage of the immune deficiency of the mice has provided an animal
      model to examine the in vivo function of transferred human or murine immune
      cells. In this review, we summarize the recent advances made in these two areas
      of SCID mouse research.

PMID- 8884427
TI  - Insights into T cell development and signal transduction provided by TCR-zeta
      chain deficient mice.
AB  - The T cell antigen receptor (TCR) transduces signals that mediate different
      responses depending on the stage of development of the T cell and the nature of
      the ligand it engages. The presence of multiple signal transducing subunits (CD3
      gamma-delta,-epsilon and zeta chain) suggests the potential to control these
      responses by altering the subunit composition of the TCR. zeta chain represents
      an especially important signalling molecule as it contains multiple signalling
      motifs within its cytoplasmic tail. The generation and analysis of zeta deficient
      (zeta-/-) and zeta-transgenic mice has provided insight into the role of zeta as
      well as the CD3 subunits in TCR surface expression, T cell activation and
      thymocyte development. Herein, we discuss the results from such experiments which
      suggest distinct roles for zeta chain and the CD3 components at different stages
      of T cell development.

PMID- 8884428
TI  - Repertoires of antigen receptors in Tdt congenitally deficient mice.
AB  - Tdt deficient mice show lack of N region in V(D)J junctions of immunoglobulin and
      T cell receptor genes and revealed that "immature recombinase" in fetal stage
      would boil down to no more than a lack of Tdt. Although particular junctions
      which are thought to be created by homology-mediated joining are frequently
      observed, one fourth of junctions lacked even one bp of overlap, indicating the
      existence of a V(D)J joining pathway that is homology independent. Lymphocyte
      repertoire which express VH81X gene without N region is negatively selected,
      which shows that the repertoire of Tdt deficient mice is not a truly fetal
      repertoire. Positive selection of thymocytes is more efficient in Tdt deficient
      mice. Furthermore Tdt-/- mice produce significant amounts of anti-dsDNA
      antibodies as Tdt+/+ mice, indicating that increased diversity of the third
      complementarity-determining region (CDR3) by Tdt is not essential for the
      expansion of precursor B cells programmed to produce anti-DNA antibodies.

PMID- 8884429
TI  - Immunoglobulin deficient mice generated by gene targeting as models for studying
      the immune response.
AB  - B cell deficient animals obtained by various strategies of gene targeting were
      used to study the B cell development and examine the role of different immune
      compartments in the immune response to microbes. Study of muMT, JHD, lambda 5T
      and JHT models of B cell deficiency, was essential in order to understand the
      role of pre-B cell receptor in B cell development, allelic exclusion and variable
      gene rearrangement regulation. In the immune response to influenza virus, a
      protective role of T cells in a total absence of B cell compartment, was revealed
      by studying the JHD -/- model. Further, it was established that a T cell
      compartment is sufficient to mediate the recovery from influenza infection.
      Examination of immune response in muMT and JHD models of definitive B cell
      deficiency to various blood stage Plasmodia species, showed that whereas B cells
      are not required for recovery from infection with P. chabaudi adami, P. vinckei
      petteri and P. chabaudi chabaudi (CB), B cell compartment is important in the
      later stages of infection with P. chabaudi chabaudi (AS). Studies carried out in
      muMT model suggested a possible role for T gamma delta subpopulation in the
      immune response to blood stage malaria parasite. B cell deficiency models are
      valuable for understanding the normal and pathological immune response. Studies
      carried out in muMT model indicated that T cell responses are not significantly
      affected in the absence of B cells. These data can neither rule out a role for B
      cells in T cell priming, nor in triggering an effective T cell help for humoral
      response. Study of double homozygous mice deficient for B cells and FAS or IL-2
      gene, pinpointed the role of B cells in pathogenesis of lupus-like nephritis and
      vasculitis from lpr mouse and in hemolytic anemia from IL-2 -/- mouse model,
      respectively.

PMID- 8884430
TI  - The surrogate light chain in mouse B-cell development.

PMID- 8884431
TI  - The lambda B cell repertoire of kappa-deficient mice.
AB  - Analysis of the B cell repertoire is complicated by the huge diversity inherent
      in the germ line determined combinatory. Making use of knockout technology, kappa
      deficient mice have been obtained. They constitute a shrewd model to follow the
      expression of an Ig minilocus, such as the lambda one, in the normal condition
      compared with classical transgenic models. Indeed, in contrast to wild type mice,
      in which only 5% of lambda B cells are produced, these mutant mice exclusively
      produce lambda positive B cells. Although, the lambda locus is well characterized
      and has a relatively simple organization, the mechanistic and selective pressures
      that govern its utilization are still poorly understood. The analysis of the
      lambda B cell repertoire in kappa-deficient mice, should therefore bring more
      conclusive informations. Here we present the lambda subtype distribution in the
      various cellular compartments of the kappa-deficient mice, and discuss the rules
      that can be responsible for this distribution. Our recent data indicate that the
      lambda subtype proportions in the bone marrow and the spleen result, for the
      major part, from mechanistic processes (i.e., recombinase accessibility,
      production of V-J functional joint and H/L pairings) while the lambda proportions
      found in the peritoneal cavity ensue from selective processes. Finally, the
      capacity to respond to various antigens is discussed from such a generated lambda
      B cell repertoire.

PMID- 8884432
TI  - Multiple loss of effector cell functions in FcR gamma-deficient mice.
AB  - Immunoglobulin Fc receptor (FcR) gamma subunit is a component of low affinity
      receptor for IgG, Fc gamma RIII, as well as high affinity receptor for IgE, Fc
      epsilon RI. This subunit is required for efficient surface expression of these
      FcRs on various cells in immune system. The FcR gamma-deficient mice, generated
      by gene targeting in embryonic stem cells, exhibit multiple defects in FcR
      mediated effector cell responses, including absence of phagocytic activity
      against opsonized red blood cells by activated macrophages, loss of antibody
      dependent cell-mediated cytotoxicity manifested by IL-2-induced splenic NK cells,
      and unresponsiveness of mast cells to crosslinking of IgE on these cells. These
      results demonstrate an indispensable role of FcR gamma for functional expression
      of FcRs, and clearly indicate the importance of Fc gamma RIII as well as Fc
      epsilon RI for these effector functions. Since FcR gamma-deficient mice is unable
      to mount the type II and type III hypersensitivity reactions, it is suggested
      that FcRs play pivotal roles in initiating these reaction cascades. The mutant
      mice should prove to be useful in evaluating FcRs in various humoral and cellular
      immune responses, and in developing new strategies for treatment of
      immunodeficiency as well as autoimmune disorders.

PMID- 8884433
TI  - The productivity of physician assistants and nurse practitioners and health work
      force policy in the era of managed health care.
AB  - Managed care is spreading rapidly in the United States and creating incentives
      for physician practices to find the most efficient combination of health
      professionals to deliver care to an enrolled population. Given these trends, it
      is appropriate to reexamine the roles of physician assistants (PAs) and nurse
      practitioners (NPs) in the health care workforce. This paper briefly reviews the
      literature on PA and NP productivity, managed care plans' use of PAs and NPs, and
      the potential impact of PAs and NPs on the size and composition of the future
      physician workforce. In general, the literature supports the idea that PAs and
      NPs could have a major impact on the future health care workforce. Studies show
      significant opportunities for increased physician substitution and even
      conservative assumptions about physician task delegation imply a large increase
      in the number of PAs and NPs that can be effectively deployed. However, the
      current literature has certain limitations that make it difficult to quantify the
      future impact of PAs and NPs. Among these limitations is the fact that virtually
      all formal productivity studies were conducted in fee-for-service settings during
      the 1970s, rather than managed care settings. In addition, the vast majority of
      PA and NP productivity studies have viewed PAs and NPs as physician substitutes
      rather than as members of interdisciplinary health care teams, which may become
      the dominant health care delivery model over the next 10-20 years.

PMID- 8884434
TI  - Allied health workforce shortages: the systemic barriers to response.
AB  - Over the last decade, the increasingly severe workforce shortages developing in
      some allied health professions have drawn the attention of university,
      government, and institutional researchers and policymakers. A 1991 American
      Hospital Association survey shows allied health professions dominating the
      "vacancy rate" list, with physical therapy (PT) and occupational therapy (OT) at
      the top. Separate surveys have documented growing shortages in the OT and
      Certified Registered Nurse Anesthetist (CRNA) areas. According to a recent survey
      by the South Carolina Hospital Association, hospital vacancy rates in OT and PT
      are particularly severe, but there are also significant shortages in the CRNA and
      Medical Technologist (ASCP) subfields. The imperatives of cost containment are
      increasing the demand in South Carolina and elsewhere for rehabilitative and
      outpatient care provided by many allied health professionals, but there is
      growing concern that the educational system will not be able to respond
      adequately to these growing workforce needs. These predictions of growing
      shortages are further confirmed by recent occupational forecasts issued by the US
      Bureau of Labor Statistics. Allied health researchers do not completely agree on
      the reasons for the development of subfield shortages, or on how severe they
      really are. Improving alternative career prospects for females low public and
      professional images, and employee burnout, among other factors, have been
      suggested. A survey of the allied health literature shows four additional broad
      areas of investigation.

PMID- 8884435
TI  - The ethics of managed care: challenges to the principles of relationship-centered
      care.
AB  - Health care reform involves ethical issues on many levels. First, the impetus to
      reform the health care system stems in large part from concerns about equity,
      just distribution of goods and services, and commitments to one another in
      society. Health care itself is more than a commodity, it is a personal healing
      activity carried out through institutions that embody values such as respect for
      persons, the value of human life, and duties to care for individuals who suffer.
      These issues fall under major overarching concerns on the macro level. Reform,
      however, often functions as a euphemism for changing the health care system to
      provide greater profitability, and for controlling costs. Admittedly, such
      changes can be disguised under reforming the health care system, and indeed, some
      of them are capable of enhancing and simultaneously making more efficient, our
      care for one another when sick. Most changes, nonetheless, are clearly driven
      from less noble ideals. Every schema for providing care also embodies values
      since these schemas presuppose various competing notions of justice and equity.
      Further, they may endanger long-held values of health care providers in meeting
      the needs of patients. As part of state or local-level changes in the health care
      system, issues in this category can be called micro level concerns. when all the
      changes impact on individuals, either providers of care, or the patients
      themselves, then the issues are of concern on the personal level. This essay,
      therefore, examines ethical issues presented by managed care networks on the
      macro, micro, and individual level, with special attention paid to the health
      care relationship. The subtitle of the essay points out the focus of the
      discussion on the impact of these changes for more traditional models of
      relationship-centered care.1 In particular, the essay concentrates on health
      providers, including allied health professionals, that in the past were grouped
      into the category of primary care givers but ought to be called first-level care
      givers today.

PMID- 8884436
TI  - Health care teams as metaphors: a preliminary study.
AB  - This pilot study attempted to uncover similarities and differences in perceptions
      of health care teams by the professionals who work in them and are affected by
      them. This study used a convenience sample of 125 health professionals from 14
      disciplines to explore the types of general metaphors and sports metaphors that
      they apply to health care teams. Data were analyzed by gender, type of metaphor,
      and stated reasons for choosing a particular metaphor. Fifteen themes emerged
      from the analysis. In response to a question about the metaphors that they apply
      to teams, health professionals identified more nonsports than sports metaphors.
      There was no difference between males and females in the application of sports
      metaphors as general metaphors for teams. Also, respondents reported using
      different metaphors in current practice than those they had used at the end of
      their formal professional training. This study demonstrates that many health
      professionals apply unidimensional metaphors to a dynamic and complex process.
      The findings suggest that trainers can help team members expose and develop their
      metaphors to more fully encompass the complexities of the health care team.

PMID- 8884437
TI  - Allied health faculty attitudes toward rural clinical practice.
AB  - Research findings of allied health practitioners' attitudes toward rural practice
      are limited. The purpose of this study was to identify attitudes of faculty
      members in a school of allied health toward rural vs. urban living, clinical
      education, and practice. A survey consisting of demographic and attitudinal
      questions was mailed to 233 faculty representing five professions. The response
      rate was 63.5%. The majority viewed rural living as having both positive and
      negative aspects. Placement of clinical students in rural areas was seen as
      enhancing rural recruitment. Rural professional issues were viewed as mixed with
      the most positive aspect being greater intellectual challenge. There were a few
      significant attitude differences by gender, age, years of experience, profession,
      hometown location, and practice location site. The findings of this study
      generally support previous research and contribute additional knowledge regarding
      attitudes toward rural practice. Further studies of allied health professionals
      appear warranted.

PMID- 8884438
TI  - Primary total hip arthroplasty with the Karl Zweymuller first-generation
      cementless prosthesis. A 5- to 9-year retrospective study.
AB  - A consecutive series of 72 primary total hip arthroplasties were performed in 70
      patients using the first-generation Zweymuller cementless titanium press-fit
      femoral and threaded acetabular components (AlloPro, Baar, Switzerland). Twelve
      hips were excluded from the study because of insufficient follow-up evaluation,
      including one patient who underwent a socket revision within the first 2 weeks.
      Sixty total hip arthroplasties with an average follow-up period of 80 months
      (range, 60-108 months) were retrospectively reviewed. Clinical results were
      graded excellent or good in 54 cases (90%), fair in 3 (5%), and poor in 3 (5%)
      with 2 early implant failures (1 acetabular cup and 1 femoral stem in 2 hips).
      Cumulative survival rates at the 6- to 7-year interval, with failure defined as
      revision and/or loosening are 98.47% (SD, 2.0%) for the femoral component (1
      single septic and loose stem, revised at 5 years), 97.08% (SD, 2.72%) for the
      screw ring (2 unstable but only 1 revised), and 95.56% (SD, 3.36%) for both
      components. This encouraging experience with the first-generation prosthesis
      supports the rationale for continued use of the new Zweymuller Alloclassic stem
      and open-back screw ring available since 1988.

PMID- 8884439
TI  - Clinical and radiographic outcome of a cementless, titanium, plasma spray-coated
      total hip arthroplasty femoral component. Justification for continuance of use.
AB  - Between 1984 and 1986, 177 nonconsecutive, primary total hip arthroplasties were
      performed in 150 patients using the Mallory-Head Porous femoral component
      (Biomet, Warsaw, IN) inserted without cement. Average time to follow-up
      evaluation for the entire population (including all early revisions) was 76
      months (6.3 years). There were 10 revisions (6%) with an average time to revision
      of 50 months (4.2 years). Two revisions were for component undersizing; three
      revisions were for aseptic loosening; four revisions were for acetabular
      component failure and one revision was due to a femoral fracture secondary to
      trauma. At the most recent follow-up visit, the average Harris hip score for all
      hips increased from 41.5 before surgery to 86.8 (P < .001). Radiographic
      assessments yielded an average Engh fixation score of 20.7. The Kaplan-Meier
      survival estimate for the average time to follow-up evaluation was 0.98. Based on
      our patient selection criteria and excellent intermediate clinical and
      radiographic results, the initial design strategies of the Mallory-Head Porous
      femoral prosthesis have been confirmed.

PMID- 8884440
TI  - Acetabular revision using a bone-ingrowth total hip component in patients who
      have acetabular bone stock deficiency.
AB  - The clinical and radiologic results of acetabular revision using a porous
      titanium-mesh metal-backed acetabular component fixed to the pelvis with screws
      were studied in 30 consecutive patients (32 hips) who had moderate or severe
      acetabular bone loss. All of the acetabula were classified as type III or IV
      according to the American Association of Orthopaedic Surgeons' acetabular grading
      system. Particulate autologous or allogenic bone-graft was used in 75% of the
      reconstructions. The mean follow-up period was 69 months (range, 46-109 months).
      Three acetabular components (9%) were rerevised for aseptic loosening at an
      average of 64 months, including one patient who had a primary diagnosis of
      radiation necrosis of the ilium. The average Harris hip score for the remaining
      29 hips rose from 46 to 81. The radiologic failure rate was 3% (1 of 29 unrevised
      hips) for a total failure rate of 12%. No pelvic osteolysis was seen with this
      implant. Revision of acetabula that have moderate or severe bone deficiency by a
      bone-ingrowth acetabular component fixed with screws and bone-graft appears to be
      successful in restoring bone stock and providing a stable, pain-free
      reconstruction.

PMID- 8884441
TI  - Treatment of femoral osteolysis with cementless total hip revision.
AB  - Fifty-nine total hip revision arthroplasties using cementless femoral components
      were performed in patients with focal femoral osteolytic defects before surgery.
      Clinical and radiographic review was performed at 2 to 5 years of follow-up
      evaluation. Osteolytic defects were located by Gruen zones, evaluated on
      postoperative radiographs, and classified as stabilized, progressive, regressing,
      healed, or new. There were no clinical failures in this series of patients, and
      no femoral revisions have been necessary. Progression of the lytic defects after
      revision did not occur. No new defects developed. Of the 154 preoperative
      osteolytic defects identified, 27 stabilized, 65 regressed, and 62 healed. One
      goal of revision hip surgery is to prevent osteolytic lesions from progressing,
      and this was achieved in 100% of patients in this series. Another goal of
      revision surgery is restoration of bone stock. It appears that there is a slow,
      steady remodeling of the lytic lesion that occurs with a well-fixed porous
      ingrowth prosthesis. Although this series did not show any additional benefit
      from cancellous allografting, the grafting technique did not use specifically
      designed instrumentation. Therefore, the full potential of grafting may not have
      been realized. If severe osteolysis is present, then regression or healing of
      defects can be achieved by revision to a cementless femoral component with or
      without the addition of cancellous allograft.

PMID- 8884442
TI  - Cementless total hip arthroplasties using ceramic-on-ceramic articulation in
      young patients. A minimum 5-year follow-up study.
AB  - Cementless total hip arthroplasties were performed in 25 consecutive young
      patients (27 hips), with a mean age of 36.5 years, using prostheses that offered
      ceramic-on-ceramic articulation. The median follow-up period was 75 months, with
      all hips being followed a minimum of 5 years. Revision surgery was necessary in
      one hip at 60 months for fracture of the cup. Ninety-six percent of the remaining
      hips were rated good or excellent clinically using the Harris hip scale.
      Radiographic loosening of one or both components was evident in 3 hips. There was
      no incidence of femoral or acetabular osteolysis observed at follow-up periods of
      5 to 8 years.

PMID- 8884443
TI  - Cementless ceramic hip arthroplasties in patients less than 30 years old.
AB  - Twenty-six cementless ceramic hip arthroplasties were performed in 22 patients
      with an average age of 24 years (range, 17-30 years) at the time of operation.
      One patient was lost to follow-up evaluation. Twenty-one patients (25 hips) were
      reviewed with an average follow-up period of 6.5 years (range, 4-13 years). Two
      hips had to undergo revision of the ceramic acetabular components because of
      fractures in the upper part of the cup in both. One further hip was explored
      because of persistent wound discharge, but a mass of indurated tissue was removed
      and there was no evidence of deep infection. No organisms were grown from the
      samples taken during operation. Harris hip scores were good to excellent in 64%,
      fair in 16%, and poor in 20% of cases. There was no or slight pain in 14 (56%),
      mild pain in 7 (28%), and moderate pain in 4 (16%) hips. Apart from the two
      sockets revised, progressive radiolucent lines were seen in five cups (20%) and
      significant vertical migration was present in nine cups (36%) with an average
      migration of 1.3 mm/y. In total, acetabular changes were observed in 11 cases
      (44%). Femoral stem subsidence of between 3 and 6 mm was seen in five cases
      (20%). The total number of hips showing loosening of one or both components was
      five (20%). Overall radiographic changes (migration and loosening) in one or both
      components were present in 13 hips (54%).

PMID- 8884444
TI  - Effects of distal femoral centralizers on bone-cement in total hip arthroplasty.
      An experimental analysis of cement-centralizer bonding, cement void formation,
      and crack propagation.
AB  - Distal femoral centralizers of five different designs were inserted into model
      femoral stems and cemented into closed-ended tubes simulating a proximal femoral
      canal. Specimens underwent cyclic loading from 50 to 500 lb. for 0, 1, 2, 5, and
      10 million cycles. Each specimen was then sectioned transversely at multiple
      levels to obtain serial cross-sections, beginning at the femoral stem tip and
      proceeding distally so as to include the full extent of the centralizer. The area
      of each section occupied by a centralizer and the total amount of porosity
      present in the cement surrounding the centralizers were measured using an image
      analyzer. A dye penetrant was then applied to each section to visualize cement
      cracks and areas of incomplete bonding between cement and centralizers. The
      number, length, and location of cement cracks were catalogued for each section.
      No cement cracks or lack of bonding was observed at the interface between cement
      and centralizers. There was greater porosity in the specimens containing
      centralizers than in controls without centralizers (P < .05). The cement
      surrounding two of the centralizer designs had a significantly smaller amount of
      porosity than the cement surrounding the other three designs (P < .05). The
      number of cracks did not depend on whether a centralizer was used, the type of
      centralizer, or the cycling duration. In the control specimens, failure to
      adequately plug the centralizer receptacle hole in the stem tip resulted in very
      large cement voids.

PMID- 8884445
TI  - Effect of superior and superolateral relocations of the hip center on hip joint
      forces. An experimental and analytical analysis.
AB  - With the extensive use of uncemented acetabular components in total hip
      arthroplasty, relocation of the hip center has become increasingly necessary to
      avoid bulk grafts and to promote contact between the porous prosthetic surface
      and bone. Compared with the anatomic hip center, superolateral relocation
      theoretically results in higher hip joint forces and has been shown in cemented
      acetabular components to result in an increased clinical failure rate. This study
      experimentally and analytically compared the hip joint forces in normal,
      superior, and superolateral hip center locations during both single-leg stance
      and stairclimbing, performing this comparison over a wide range of hip joint
      applied flexion moments. An advanced loading fixture was designed to allow any
      applied moment to be set independently of femoral position, incorporating all
      three major muscle groups active in stairclimbing position: extensors, abductors,
      and adductors. For all positions and moments tested, it was found that
      superolateral relocation caused significant increases in the total hip joint
      force, but did not affect the nonsagittal force component. Also, superior-only
      hip center relocation did not significantly affect the total joint force
      magnitudes or directions. The force increase on hip center lateralization can be
      attributed to a corresponding increase in the adduction moment. Results from the
      static analytical model developed supported these findings. The results of this
      study suggest that superolateral hip center relocation should be avoided and that
      superior-only relocation may be mechanically acceptable within the confines of
      the osseous anatomy of the acetabulum.

PMID- 8884446
TI  - Revision total hip arthroplasty with a retroperitoneal approach to the iliac
      vessels.
AB  - Although vascular complications during revision total hip arthroplasty are rare,
      the results can be devastating. Reports in the literature describe staged
      operations, with the first procedure being abdominal to remove cement and/or the
      acetabular component followed by a second joint reconstruction procedure. A
      protocol was developed that combines a retroperitoneal approach with revision
      total hip arthroplasty in one operative procedure in patients at risk for
      vascular injury. The patient first undergoes a retroperitoneal incision and the
      iliac artery and vein are dissected free of surrounding tissue. A silicone loop
      is placed around the iliac artery and vein and brought out through the wound. The
      wound is temporarily closed using staples. Revision total hip arthroplasty then
      proceeds in the usual fashion. If hemorrhage is encountered, bleeding can be
      rapidly controlled by tensioning the abdominal vessel loops and opening the
      incision for exposure to the vessels. No complications have been encountered in
      23 patients when using this approach.

PMID- 8884447
TI  - Surgical management of intra- and postoperative fractures of the femur about the
      tip of the stem in total hip arthroplasty.
AB  - Six techniques for the surgical management of fractures of the femur about the
      tip of the stem of a total hip arthroplasty were evaluated. Seven embalmed human
      femurs were prepared to receive the correct-size femoral component of a total hip
      system. A transverse osteotomy was performed at the level of the tip of the stem.
      Stability and strength of each reconstruction were tested on each femur under
      semidynamic loading conditions. This study showed that cementless revision to a
      long-stem prosthesis does not provide adequate stability. The highest strength
      and stability were achieved by supplementing the long-stem conversion with
      allograft struts and cable cerclage. Good results were obtained by lateral
      compression plating with unicortical screws proximally. Failure was due to pull
      out of the proximal screws.

PMID- 8884448
TI  - Natural history of femoral focal osteolysis with proximal ingrowth smooth stem
      implant.
AB  - Focal femoral osteolysis has become a prominent cause of failure of total hip
      arthroplasty. Femoral focal osteolysis is studied in 185 hips with a patched
      porous-coated titanium femoral stem. Seventy-two hips had osteolysis and 113 did
      not. Seventy-one percent of osteolysis is evident on radiographs by 6 months to 5
      years after surgery. The location is most commonly seen on an anteroposterior
      radiograph, with proximal osteolysis most common and the initial size of defects
      being greatest in zones 2, 3, 5, and 6. Progression of size is slow, with each
      focal defect averaging 0.89 mm/y. Progression of bone loss occurs more commonly
      with the occurrence of new defects rather than extension of an existing defect.
      Focal osteolysis was directly correlated with the amount of polyethylene wear.
      Osteolysis is more likely when linear polyethylene wear exceeds 0.2 mm/y or
      volumetric wear exceeds 150 mm3/y or when the patient is below age 60.
      Accelerated wear and osteolysis occur most often when the fixation of the
      arthroplasty is poor.

PMID- 8884450
TI  - Results of total knee arthroplasty following takedown of formal knee fusion.
AB  - Seventeen cases of knee fusion takedown with follow-up periods of 1 to 10 years
      have been reviewed. Two patients were re-fused for patellar tendon loss and
      sepsis. One had a chronic low-grade infection but refused re-fusion. Two patients
      who required immobilization for the first 10 days following total knee
      arthroplasty had a range of flexion of 35 degrees only. The mean range of flexion
      in the other patients in 84 degrees. Using The Hospital for Special Surgery
      rating, 29.4% scored excellent, 29.4% good, 17.6% fair, and 17.6% poor, including
      the two patients refused. Complications were found in nine patients (53%), six of
      which were resolved with further surgery. All patients preferred the mobile knee,
      but the complication rate is so high that the authors remain ambivalent about
      this procedure.

PMID- 8884449
TI  - Histologic comparison of posterior cruciate ligaments from arthritic and age
      matched knee specimens.
AB  - Twenty-four posterior cruciate ligaments (PCLs) harvested at the time of total
      knee arthroplasty (TKA) were histologically compared with an age-matched group of
      36 PCLs harvested from above-knee amputations, cadavers, and bone bank donors.
      Ligaments were considered histologically abnormal and degenerative if either
      loose, mucoid, myxoid, or cystic changes were noted. The magnitude of
      degeneration was defined as normal, slight, mild, moderate, or marked, based on
      the amount of tissue demonstrating change. Examination of the PCLs from the TKA
      group demonstrated 17% normal ligaments, 20% with mild focal changes, and 63%
      with marked degenerative changes. The control group demonstrated 45% normal
      cruciate ligaments and 33% with slight, 11% with mild, and 11% with moderate
      focal changes. No PCL from the control group showed marked changes. The overall
      degenerative changes between these two groups were found to be statistically
      significant (P < .001). This study demonstrated that the PCL obtained at the time
      of TKA is characterized by distinct histologic degenerative changes that are
      different from age-related changes (P < .001) and that the PCL is not spared
      degenerative changes in involved osteoarthritic knees. This may help explain the
      finding that the PCL in osteoarthritic knees is biomechanically abnormal. Many
      studies have reported excellent results with TKA systems that retain the PCL,
      implying that a completely normal PCL is not required or that neural input is
      sufficient for proper kinematic knee function in knees that have undergone total
      joint arthroplasty.

PMID- 8884451
TI  - Radiographic wear assessment in a total knee prosthesis. 5- to 9-year follow-up
      study of 158 knees.
AB  - One hundred fifty-eight Porous-Coated Anatomic (Howmedica, Rutherford, NJ)
      primary total knee prostheses were evaluated clinically and radiographically to
      measure the remaining thickness of the plastic insert. Anteroposterior
      radiographs were taken with the beam guided parallel to the tibial plate by a
      fluoroscope. The knees were forced into varus and valgus, and the heights of the
      medial and lateral joint spaces, respectively, were measured with a digitizing
      table. Plastic insert wear could be calculated after correction with a
      magnification error factor, established by dividing the projected width of the
      tibial plate by the true size of the used component. After a mean follow-up
      period of 84 months (range, 58-116 months), wear was significantly higher for
      patients with osteoarthritis than rheumatoid arthritis and was 1.4 mm versus 0.7
      mm medially (P < .0001) and 0.7 mm versus 0.4 mm laterally (P = .01). Wear was
      not correlated to thickness of the plastic insert or length of follow-up period.
      Young age or varus alignment contributed slightly to the amount of wear.

PMID- 8884452
TI  - Use of bone compaction in total knee arthroplasty.
AB  - This study compared the effects of bone preparation on tibial stem stability in
      total knee arthroplasty. Six pairs of fresh-frozen tibias underwent implantation
      of an 18 x 75-mm press-fit stem (minus the tibial tray). The standard press-fit
      technique was performed creating a cavity 17 mm in diameter. For the bone
      compaction technique, stainless-steel dilators were machined ranging in diameter
      from 6 to 16 mm in 2-mm increments. The technique consisted of using the dilators
      and a mallet to create a compacted tunnel in a sequential manner to 16 mm in
      diameter followed by implantation of the stem. The specimens were mounted on a
      materials testing machine and loads were applied in both planes: anteroposterior
      and mediolateral. A preconditioning load of 100 N was applied followed by a
      second 100-N load from which the stiffness (N/mm) of implantation was calculated.
      The stability of the tibial stems implanted by compaction averaged 84.7% greater
      when compared with the press-fit stems (P < .017 by multivariate analysis).

PMID- 8884453
TI  - Survivorship analysis of cemented total hip arthroplasty acetabular components
      implanted with second-generation techniques.
AB  - The clinical and radiographic results of primary cemented total hip arthroplasty
      performed by a single surgeon, with particular emphasis on the performance of
      acetabular components implanted with so-called second-generation cement
      techniques, were studied. Seventy hips with 48 metal-backed and 22 polyethylene
      acetabular components were followed for a mean of 9 years (range, 5-11.5 years).
      The clinical results were evaluated using a recognized hip score. The fixation
      status of the cemented acetabular component was evaluated using two methods of
      measuring radiolucent lines at 5 years and at the last evaluation. Acetabular
      component loosening was defined as a circumferential radiolucent line, component
      migration, or revision for loosening. This study was unable to confirm the
      findings of others that demonstrated higher failure rates with cemented metal
      backed components when compared with all-polyethylene components. The survival of
      cemented acetabular components with 28-mm head femoral prostheses was worse than
      the survival of cemented acetabular components with 22-mm femoral heads in other
      published reports, despite advances in cement techniques. Because of the high
      rate of loosening of cemented 28-mm-inner-diameter acetabular components at 5 and
      10 years, the authors no longer use these cemented components for acetabular
      reconstruction.

PMID- 8884454
TI  - Fractures through cystic lesions of the greater trochanter. A cause of late pain
      after cementless total hip arthroplasty.
AB  - Four patients who presented with sudden onset of hip pain 7 to 11 years after
      successful porous-coated cementless hip arthroplasty are described. These four
      patients were all diagnosed to have fractures through osteolytic cysts in the
      greater trochanter. One patient was seen initially with a displaced fracture of
      the greater trochanter. Two patients were treated operatively with curettage of
      the cystic area and with polyethylene exchange. One of these patients underwent
      revision of the femoral component in addition to the polyethylene exchange. Two
      patients were treated nonoperatively. The fractures treated nonoperatively have
      healed and the patients have resumed their normal activities. This report should
      stimulate an awareness of fractures through cystic lesions of the greater
      trochanter as a late cause of hip pain after porous-coated cementless hip
      arthroplasty.

PMID- 8884455
TI  - Appositional bone bridging of primary gaps in the dome area of uncemented, porous
      acetabular components.

PMID- 8884456
TI  - Early failure of Hylamer acetabular inserts due to eccentric wear.

PMID- 8884457
TI  - Clinical failure of alumina.

PMID- 8884458
TI  - The antilesion actions of anticholinergic agents on ethanol-induced injury in rat
      stomachs: the importance of gastric vascular integrity and tonicity.
AB  - 1. The antilesion actions of two antimuscarinic drugs on ethanol-induced gastric
      injury and mucosal integrity were examined in male rats. Histological
      examinations were made and gastric emptying rates determined after in vivo
      administration of the drugs to conscious rats. In anaesthetized rats, with an ex
      vivo gastric chamber, effects on gastric transmucosal potential difference,
      Evan's blue leakage and Na+ output were examined. 2. In conscious animals,
      atropine (1 mgkg-1, i.p.) and pirenzepine (1 mgkg-1, i.p.) both significantly
      reduced macroscopic lesion formation, but not microscopic damage and functional
      alterations, caused by orally administered absolute ethanol. Moreover, these
      drugs did not show any effect on the basal gastric adherent mucus level, nor the
      depleting action of ethanol on both adherent mucus and the mucosal mucus layer.
      Nevertheless, both atropine and pirenzepine significantly reduced gastric
      emptying rate. 3. In anaesthetized animals, pirenzepine but not atropine
      increased the basal transmucosal potential difference (PD); however, it could not
      prevent the ethanol-induced drop in PD. Furthermore, the inhibitory action of
      ethanol on sodium ion output from the gastric mucosa was not attenuated by these
      drugs. Pirenzepine, however, significantly lessened the increase in vascular
      permeability caused by 100% ethanol. This action was not shared by atropine. 4.
      These findings indicate that both atropine and pirenzepine exert their antilesion
      actions through the relaxation of the stomach. Pirenzepine also preserves the
      integrity of the gastric mucosal vasculature, which is distinct from the action
      of atropine. The protective action of these drugs occurs only at the macroscopic
      level.

PMID- 8884459
TI  - Propranolol stereoselectively inhibits alpha-adrenoceptor-mediated
      vasoconstriction in mesenteric arterial beds of rats.
AB  - 1. The optical isomers of propranolol were compared for their effects on pressor
      responses to adrenergic and non-adrenergic vasoconstrictors in mesenteric
      arterial beds of rats. 2. R(+)-propranolol (10(-7)-10(-5) M) had no effect on
      vessel preparations stimulated with noradrenaline, methoxamine, or arginine
      vasopressin. 3. S(-)-propranolol 10(-7) M did not alter pressor responses to
      noradrenaline. However, S(-)-propranolol 10(-6) and 10(-5) M inhibited
      vasoconstriction induced by noradrenaline. This effect was similar in the
      presence of indomethacin 3 x 10(-6) M. 4. S(-)-propranolol 10(-5) M also
      inhibited vasoconstriction induced by methoxamine, shifting the dose-response
      curves to the right, but did not affect pressor responses to arginine
      vasopressin. 5. Schild analysis for equilibrium vasoconstrictor responses to
      methoxamine indicated stereoselective competitive alpha-adrenoceptor antagonism
      by propranolol. 6. These data suggest selective inhibition of alpha-adrenoceptor
      mediated vasoconstriction by S(-)-propranolol at higher concentrations by
      competitive alpha-adrenoceptor antagonism.

PMID- 8884461
TI  - Effect of tamsulosin, a novel alpha 1-adrenoceptor antagonist, on urethral
      pressure profile in anaesthetized dogs.
AB  - 1. The effect of tamsulosin (YM617, (R) (-)-S-[2-[[2-(o
      ethoxyphenoxy)ethyl]amino] propyl]-2-methoxybenzenesulfonamide HCl), a potent and
      selective alpha 1-adrenoceptor antagonist, was examined on urethral pressure
      profile (UPP) and mean arterial blood pressure (MBP) in pentobarbital
      anaesthetized male dogs. 2. Selective alpha 1-adrenoceptor antagonists tamsulosin
      (1-100 micrograms kg-1 i.v.), prazosin (1-100 micrograms kg-1 i.v.) and bunazosin
      (1-100 micrograms kg-1 i.v.) produced a dose dependent reduction in prostatic
      pressure in the UPP. Doses required to reduce prostatic pressure in UPP by 30%
      were 3.6 +/- 0.8 (n = 8), 6.9 +/- 1.5 (n = 8) and 4.6 +/- 0.9 (n = 8) micrograms
      kg-1 i.v., respectively. At the highest dose, tamsulosin exerted less hypotensive
      effect than prazosin and bunazosin. 3. The calcium antagonist nicardipine (0.1-10
      micrograms kg-1 i.v.) and angiotensin converting enzyme inhibitor captopril (10
      1,000 micrograms kg-1 i.v.) reduced MBP in a dose dependent manner, but exerted
      no effect on prostatic pressure in the UPP. The diuretic trichloromethiazide (1
      100 micrograms kg-1 i.v.) exerted no effect on UPP or MBP. Treatment with
      nicardipine (3 micrograms kg-1 i.v.), captopril (100 micrograms kg-1 i.v.) or
      trichlormethiazide (100 micrograms kg-1 i.v.) did not affect relaxant effect of
      tamsulosin on prostatic pressure in UPP, or potentiate its hypotensive effect. 4.
      These results suggest that the alpha 1-adrenoceptor regulates urethral pressure
      as well as blood pressure in anaesthetized dogs, and that alpha 1-adrenoceptor
      antagonists may be useful in the treatment of micturition disorders associated
      with benign prostatic hyperplasia. In addition, as tamsulosin decreased urethral
      pressure with less hypotension, and as its effect was not influenced by treatment
      with hypotensive drugs, it may be a useful drug for the treatment of micturition
      disorders with few cardiovascular side effects.

PMID- 8884460
TI  - Characterization of the apamin- and L-nitroarginine-resistant NANC inhibitory
      transmission to the circular muscle of guinea-pig colon.
AB  - 1. The aim of this study was a pharmacological characterization of the multiple
      NANC inhibitory transmission systems producing relaxation of the circular muscle
      of guinea-pig proximal colon. In the presence of atropine (1 microM),
      guanethidine (3 microM) and of the tachykinin NK1 and NK2 receptor antagonists,
      SR 140333 (0.3 microM) and MEN 10627 (1 microM), respectively, electrical field
      stimulation (EFS) produced a frequency-dependent (0.1-3 Hz) relaxation. During a
      cumulative frequency-response curve, the maximal relaxant effect was produced at
      3 Hz and approached the maximal relaxation to 1 microM isoprenaline. In the
      presence of both apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM),
      EFS failed to evoke relaxation up to 1 Hz; at 1-10 Hz, a slowly developing
      relaxation ensured which approached 50% of the Emax to isoprenaline. The EFS
      evoked NANC relaxation, either in the presence or absence of apamin and L-NOARG,
      was unaffected by in vitro capsaicin pretreatment (10 microM for 15 min). 2.
      Three protocols of EFS were developed for further pharmacological analysis: (a)
      EFS at 1 Hz for 5 s in the presence of L-NOARG, producing a transient fast apamin
      sensitive relaxation; (b) EFS at 1 Hz for 5 s in the presence of apamin,
      producing a transient fast L-NOARG-sensitive relaxation; and (c) EFS at 10 Hz for
      5 s in the presence of both apamin and L-NOARG, producing a transient but slowly
      developing and more sustained relaxation. 3. The neutral endopeptidase inhibitor,
      thiorphan (1-10 microM), enhanced and prolonged the apamin- and L-NOARG-resistant
      NANC relaxation produced by EFS at 10 Hz, without affecting that evoked at 1 Hz
      in the presence of apamin or L-NOARG. The angiotensin converting enzyme
      inhibitor, captopril (1-10 microM) was without effect. 4. The cAMP analogue
      inhibitor of protein kinase A, Rp-cAMPs (100-300 microM) significantly reduced
      and shortened the NANC relaxation produced by 10 Hz EFS in the presence of L
      NOARG without affecting that produced by 1 Hz EFS in the presence of apamin or L
      NOARG. 5. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid
      (CPA, 3-10 microM for 60 min) abolished the 1 Hz EFS-induced relaxation in the
      presence of L-NOARG, and greatly inhibited that produced by 10 Hz EFS in the
      presence of both apamin and L-NOARG. The relaxation produced by 1 Hz EFS in the
      presence of apamin was inhibited by about 32% at 10 microM only. 6. Nifedipine (1
      microM) did not affect the EFS-induced NANC relaxations. In the presence of
      nifedipine, tetraethylammonium (TEA, 1 mM) enhanced the 1 Hz EFS-induced
      relaxation in the presence of L-NOARG (158% of control) and that produced by 10
      Hz EFS in the presence of apamin and L-NOARG (215% of control) while that evoked
      by 1 Hz EFS in the presence of apamin was slightly affected (109% of control). 7.
      In the presence of atropine, guanethidine, SR 140333 and MEN 10627, bath
      application of human vasoactive intestinal polypeptide (VIP, 0.1 nM-10 nM)
      produced a concentration-dependent, slowly developing relaxation of colonic
      strips. The relaxation to VIP was unaffected by apamin (0.3 microM), L-NOARG (100
      microM), nifedipine (1 microM) or nifedipine plus TEA (1 mM); it was inhibited by
      CPA (10 microM) and Rp-cAMPs (100 microM) and was potentiated by thiorphan (10
      microM). 8. The putative VIP receptor antagonist, VIP(10-28) (10 microM) did not
      affect the VIP-induced relaxation nor the NANC relaxation to 10 Hz EFS in the
      presence of apamin and L-NOARG. 9. The present findings provide evidence that
      three distinct NANC inhibitory mechanisms mediate relaxation of the circular
      muscle of the guinea-pig proximal colon. The first system provides a fast
      relaxation in response to low frequency of stimulation and may involve the action
      of a transmitter(s) (possibly ATP) which mobilizes intracellular Ca2+ from
      sarcoplasmic reticulum leading to the activation of apamin-sensitive K+ channels.
      The second system likewise provides a fast relaxation of the colon in

PMID- 8884462
TI  - Urinary dopamine outputs do not rise in healthy Chinese subjects during gradually
      increasing oral sodium intake over 8 days.
AB  - 1. All previous studies on the effects of changes in sodium intake on the renal
      dopamine (DA) response (increase in urinary DA output) have used sudden, large
      changes in oral sodium intake. The present study was designed to study the role
      of renal DA and the suppression of sympathetic nervous system activity in the
      natriuretic response to step-wise, gradual increases in sodium intake. 2. Seven
      healthy, male Chinese subjects (23-25 years) were studied. During the 12-day
      study period (day -3 to 8), subjects were given the same basic diet containing
      1900 calories, 75 g protein, 20 mmol sodium and 45 mmol potassium. From days 1 to
      8, subjects also received 'Slow sodium' tablets (Ciba-Geigy) equivalent to 50
      mmol on day 1, 100 mmol on day 2, 150 mmol on day 3,200 mmol on day 4, 250 mmol
      on day 5, and 300 mmol on days 6 to 8. Body weight was recorded and blood
      pressure was measured after lying supine for 10 min in the morning before
      breakfast on entry and at the end of the low and high sodium intake periods.
      Urine was collected for 24 h on day -3 and from days 0 to 8 for the measurement
      of sodium, potassium, creatinine, free DA and free noradrenaline (NA). 3. After 4
      days of sodium restriction, mean arterial pressure (mean +/- SEM) had decreased
      from 83.0 +/- 1.3 to 79.4 +/- 0.5 (P < 0.05) and body weight from 70.2 +/- 3.1 to
      68.3 +/- 3.0 (P < 0.02). Following sodium loading, MAP and body weight did not
      change, but pulse rate had decreased from 64.1 +/- 2.8 to 57.4 +/- 2.6 (P <
      0.02). 4. There was a 13-fold increase in sodium excretion (P < 0.02) by the last
      day of the high sodium intake period. There were no significant changes in urine
      volume and urinary excretion of potassium, creatinine and free DA throughout the
      high sodium intake period. In contrast, there was a 19.9-26.5% decrease in urine
      NA 4 and 6 days after the start of the increase in sodium intake. 5. Healthy
      Chinese subjects do not have a renal DA response to gradually increasing sodium
      intake over an 8-day period. Any tendency to hypervolaemia-related rises in blood
      pressure during the high sodium intake period may be partly offset by a reduction
      in sympathetic nervous system activity.

PMID- 8884463
TI  - Effect of the Ca(2+)-channel agonist Bay K 8644 on the contractile responses in
      human placental veins.
AB  - 1. The aim of the present study was to analyse, in segments of human placental
      veins, the effect of the Ca2+ channel agonist Bay K 8644 (0.1 microM) and Ca2+
      channel antagonists nifedipine (0.1 microM) and diltiazem (1 microM) on vascular
      contractility and 45Ca2+ uptake. 2. The Ca2+ channel agonist Bay K 8644 (0.1
      microM) caused small concentration dependent contractions that were increased by
      a moderate membrane depolarization with 7.5 mM K+. This increase was reversed by
      nifedipine and diltiazem. Ca2+ addition to segments previously depolarized with
      75 mM K+ and exposed to a Ca(2+)-free medium caused contractile responses that
      were increased by 0.1 microM Bay K 8644; such an increase was blocked by 0.1
      microM nifedipine and 1 microM diltiazem. 3. K+ and 5-HT induced concentration
      dependent contractile responses which were increased by Bay K 8644 (0.1 microM).
      Both 0.1 microM nifedipine and 1 microM diltiazem inhibited the increasing effect
      of Bay K 8644. Bay K 8644 (30 nM and 0.1 microM) caused an enhancement in 45Ca2+
      accumulation over the basal value, that was increased by membrane depolarization
      with K+ (7.5, 15 and 30 nM) and inhibited by nifedipine (0.1 microM). K+ (15 and
      30, but not 7.5 mM) and 5-HT (1 microM) induced 45Ca2+ uptake over the basal
      level that was increased by Bay K 8644 (0.1 microM). Such an increase was
      antagonized by nifedipine (0.1 microM). 4. These data indicate that: (1) a small
      depolarization with K+ is needed for Bay K 8644 to be able to produce consistent
      contractile responses, suggesting that voltage gated Ca2+ channels (VGCCs) are
      not activated in a basal situation in placental veins; (2) the increase of 5-HT
      contraction by Bay K 8644 may be produced by either the capability of this amine
      to depolarize the membrane of smooth muscle cells and subsequent facilitation of
      Ca2+ influx through VGCCs or direct activation by Bay K 8644 of receptor (5-HT)
      operated Ca2+ channels (ROCs), and (3) the increasing effect of Bay K 8644
      appears to be due to a Ca2+ entry activation through VGCCs.

PMID- 8884464
TI  - Inhibition of calcium influx and tonic response to K+ of intestinal smooth muscle
      by hydralazine.
AB  - 1. Evidence concerning the mechanism of the inhibition of contraction caused by
      hydralazine has been sought in ileal longitudinal muscle and taenia coli of
      guinea-pig. Hydralazine (10(-3)-3 x 10(-3) M) markedly inhibited K+ (60 mM)
      induced tonic response with smaller effects on the phasic response in the ileal
      muscle. However, 10(-2) M hydralazine completely abolished both responses. 2.
      Hydralazine increased the threshold for Ca2+ induced contraction in Ca2+ free, K+
      depolarized taenia coli and reduced the maximal response size. A low
      concentration (3 x 10(-10) M) of nifedipine, an L-type Ca2+ channel blocker,
      further caused a parallel shift to the right in the presence of hydralazine in
      the concentration-response curves obtained with Ca2+ 3. Hydralazine caused a
      significant decrease in Ca2+ uptake measured by the lanthanum method during the
      K+ induced tonic response in ileal muscle; however, it did not affect the Ca2+
      efflux. 4. In ileal muscle fibres treated with Triton-X-100, in which the Ca2+
      release sites are destroyed, 10(-3) M hydralazine had no effect on the
      contractions induced by 10(-5) M Ca2+; however, hydralazine at a higher
      concentration (10(-2) M) had a slight inhibitory effect on the contraction. 5.
      The present finding indicates that the inhibitory action on contractions produced
      by hydralazine may result mainly from the interference of calcium permeability at
      the cell membrane in ileal muscle. There is the possibility that hydralazine of
      higher concentrations may have a minor action on the contractile system.

PMID- 8884465
TI  - Changes in chromatin structure and nuclear matrix association of the rat
      cytochrome P450 2B1/2 (CYP2B1/2) gene following induction with phenobarbital.
AB  - Treatment of rats with phenobarbital has been shown to result in an enormous
      increase in CYP2B1/2 mRNA levels in the liver. This study was performed in order
      to relate this effect of phenobarbital treatment to changes in the chromatin
      structure of the CYP2B1/2 gene. Phenobarbital treatment was shown to be
      associated with a twofold increase in DNase I sensitivity of the CYP2B1/2 gene in
      the liver. In addition, induction of the CYP2B1/2 gene transcription by
      phenobarbital resulted in a marked enrichment in the liver of CYP2B1/2 sequences
      in the nuclear matrix as compared to the matrix-free fraction. Control studies
      with the CYP1A2 gene, of which the transcriptional activity is not influenced by
      phenobarbital, did not show any changes in both DNase I sensitivity and matrix
      association upon phenobarbital treatment. Furthermore, after phenobarbital
      treatment, no changes in DNasel sensitivity or nuclear matrix association of the
      CYP2B1/2 gene were observed in the kidney. These data indicate a direct, positive
      correlation between the structure of the rat CYP2B1/2 gene and its activity.

PMID- 8884466
TI  - DNA breakage by uric acid and Cu(II): binding of uric acid to DNA and biological
      activity of the reaction.
AB  - Uric acid is present in human plasma in relatively high concentrations and is
      considered to be a natural physiological antioxidant. We have earlier shown that
      in the presence of Cu(II) and molecular oxygen, uric acid causes strand breakage
      in DNA. In this article, we show that uric acid fluorescence is quenched by
      addition of DNA, indicating the formation of uric acid-DNA complex. Uric acid
      Cu(II)-mediated DNA strand scission is capable of bacteriophage inactivation and
      such inactivation is mediated through reduction of Cu(II) to Cu(I) and the
      generation of oxygen-derived radicals. It is indicated that the DNA breakage is
      repaired in E. coli and involves the repair of DNA polymerase.

PMID- 8884467
TI  - Interaction of salicylate and ibuprofen with the carboxylic acid: CoA ligases
      from bovine liver mitochondria.
AB  - Neither salicylate nor ibuprofen was a substrate or inhibitor of the long-chain
      fatty acid:CoA ligase. In contrast, all three xenobiotic-metabolizing medium
      chain fatty acid:CoA ligases (XL-I, XL-II, and XL-III) had activity toward
      salicylate. The K(m) value for salicylate was similar for all three forms (2 to 3
      microM), but XL-II and XL-III had higher activity at Vmax. For ibuprofen, only XL
      III catalyzed its activation, and it had a K(m) for ibuprofen of 36 microM.
      Studies of salicylate inhibition of XL-I, XL-II, and XL-III revealed that it
      inhibited the benzoate activity of all three forms with K1 values of ca. 2
      microM, which is in agreement with the K(m) values obtained with salicylate as
      substrate. Kinetic analysis revealed that salicylate conjugation by all three
      forms is characterized by substrate inhibition when salicylate exceeds ca. 20
      microM. Substrate inhibition was more extensive with XL-I and XL-III. Previous
      work on the ligases employed assay concentrations of salicylate in the range of
      0.1 to 1.0 mM, which are clearly inhibitory, particularly toward XL-I and XL-III.
      Thus, activity was not properly measured in previous studies, which accounts for
      the fact that salicylate conjugation was only found with one form, which is most
      likely XL-II since it has the highest Vmax activity and shows the least amount of
      substrate inhibition. Studies with ibuprofen indicated that it inhibited XL-I, XL
      II, and XL-III, with KI values being in the range of 75-125 microM. The short
      chain ligase was inhibited by both salicylate and ibuprofen with KI values of 93
      and 84 microM, respectively. It was concluded that pharmacological doses of
      salicylate, but not ibuprofen, will affect the metabolism of medium-chain fatty
      acids and carboxylic acid xenobiotics and that the previously described
      mitochondrial ibuprofen:CoA ligase activity is attributable to XL-III.

PMID- 8884468
TI  - Transforming growth factor-beta 1 inhibits regeneration of renal proximal tubular
      cells after oxidant exposure.
AB  - Transforming growth factor-beta (TGF-beta), a regulatory cytokine expressed in
      the kidney, plays a role in nephrogenic repair. This study utilized a chemical
      model of renal proximal tubule cellular injury and regeneration to investigate
      the effects of TGF-beta 1 on regeneration. Confluent monolayers of rabbit renal
      proximal tubular cells (RPTC) in primary culture exposed to the oxidant t
      butylhydroperoxide (800 microM TBHP) for 1.5 hours were 24% confluent after 24
      hours. Confluency increased to 50% 4 days after TBHP exposure. Recovery of
      monolayer confluency was associated with increased monolayer protein but not with
      DNA content. Daily treatment of injured monolayers with TGF-beta 1 inhibited the
      recovery of monolayer confluency and inhibited recovery of protein content in a
      concentration-dependent manner (0.02-1 ng/mL). DNA content of injured monolayers
      was not altered by TGF-beta 1. A single treatment of injured monolayers with 0.2
      ng/mL (8 pM) TGF-beta 1 inhibited recovery of monolayer confluency and protein
      content without altering monolayer DNA content. These data show that a single 24
      hour exposure to a low concentration (8 pM) of TGF-beta 1 inhibits regeneration
      of renal proximal tubule cell monolayers following oxidative injury by
      inhibiting, in part, cellular migration/spreading.

PMID- 8884469
TI  - Glutathione S-transferases in the Japanese quail: tissue distribution and
      purification of the liver isozymes.
AB  - Cytosolic glutathione S-transferase (GST) activities toward 1-chloro-2,4-dinitro
      benzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EA), 1,2
      epoxy-3-(p-nitrophenoxyl)propane (EPNP), trans-4-phenyl-3-buten-2-one(t-PBO),
      delta 5-androstene-3,17-dione (ASD) and trans-stilbene oxide (t-SO); cytosolic
      glutathione peroxidase activity toward cumene hydroperoxide (CuOOH); and
      microsomal GST activity toward CDNB were examined in liver, kidney, brain, and
      lung of adult male and female Japanese quail. In all cases, the renal specific
      activity per milligram protein was higher than the hepatic activity and was the
      highest among the four tissues examined. No consistent sex differences in GST
      activity were observed. The GSTs were purified from quail liver cytosol by S
      hexylglutathione and glutathione affinity chromatography. Total GSTs eluted from
      the S-hexylglutathione affinity column were further separated by
      chromatofocusing, and the microheterogeneity of the GST isozymes was shown by
      high-resolution native isoelectrofocusing (IEF) in polyacrylamide slab gels and
      by SDS-PAGE. Five subunits were identified: QL1 (30.5 kDa), QL2 (27.2 kDa), QL3a
      (26.8 kDa), QL3b (26.5 kDa), and QL4 (25.5 kDa). Western blot analysis revealed
      that QL1 and QL2 reacted with antibodies raised against the rat Mu class GSTs
      (Yb1 and Yb2), and QL3a and QL3b reacted with those raised against the Alpha
      class (rat Ya and mouse a). Substrate specific activity of each isoform was
      determined with CDNB, DCNB, CuOOH, EA, t-PBO, ASD, and t-SO. QL3a and QL3b have
      high reactivity toward CuOOH, while QL1 and QL2 showed high activity toward t-SO.
      The N-terminal amino acid sequence of QL2 was identical to that of the chicken Mu
      class GST subunit CL2. However, no sequence was obtained with QL1 due to possible
      N-terminal blockage.

PMID- 8884470
TI  - Comparative left-right mechanical testing of cancellous bone from normal femoral
      heads.
AB  - In order to assess the potential influence of various physical or chemical
      treatments on bone grafts, and in particular, on femoral heads to be used as bone
      grafts, the mechanical symmetry of the femoral head was investigated. Pairs of
      proximal human femora were harvested and transversally sliced using a coordinate
      system to orient correctly the head. After being embedded and polished, bone
      slices were loaded to failure between two steel columns (6 mm of diameter) in a
      sequential and symmetrical manner for both heads. From ten pairs, 592 mechanical
      assays on the cancellous bone of femoral heads were performed. There was a high
      variation in the mechanical properties of the specimens from the different
      donors. However, no statistical difference could be observed within each pair
      when side-to-side symmetry was tested for the different mechanical
      characteristics. Ultimate stress at failure and stiffness were also highly
      correlated for each mirror location of each pair. Provided that an accurate and
      reproducible method of slicing femoral head can be achieved, an excellent
      mechanical symmetry is observed using a static compressive test. Such a method
      could be used to determine the mechanical influence of any treatment applied to
      bone.

PMID- 8884471
TI  - Ultrasound velocity measurement in long bones: measurement method and simulation
      of ultrasound wave propagation.
AB  - A new method for the measurement of ultrasound velocity in long bones is
      presented. The method can be applied in vitro as well as in vivo. It
      automatically corrects for the influence of soft tissue, such that the real
      velocity in bone is obtained. In a series of simulation experiments, hypotheses
      on the followed wave path were verified. A very good agreement was found between
      the measurement obtained in the experimental set-up and the values calculated for
      the hypothesised wave path in the experimental structure. These simulations
      revealed the feasibility of the technique to determine the velocity in a local
      site of the structure. Clinical applications of this technique include the
      monitoring of callus consolidation after fracture and the detection of bone
      degenerative diseases such as osteoporosis.

PMID- 8884472
TI  - Modeling axi-symmetrical joint contact with biphasic cartilage layers--an
      asymptotic solution.
AB  - The articular contact surfaces in human and animal joints are highly variable.
      Articular cartilage thickness and the material properties of the cartilage vary
      as a function of location in the joint and may also change in the pathologic
      state. In order to study practical joint contact problems, we extended the model
      for the contact of two biphasic cartilage layers proposed by Ateshian et al. [J.
      Biomechanics 27, 1347-1360 (1994)] by combining the assumption of the kinetic
      relationship from classical contact mechanics with the joint contact model for
      biphasic articular cartilage. In order to illustrate the characteristics of the
      proposed model, the contact problem was solved numerically for different
      curvatures of the contact surfaces, and for different thicknesses and material
      properties of the cartilage layers. Each cartilage layer was assumed to have
      constant thickness within the contact region. The contact radius, the relative
      displacement between the contacting bodies, contact pressure, and the stress
      distributions within the cartilage layers were calculated by applying a step load
      for a time period of 200 s. The contact radius was found to be sensitive to the
      change in thickness of the cartilage, and was not very sensitive to the change in
      the material property of the cartilage. The peak effective stress and the maximal
      shear stress were predicted to occur at the cartilage-bone interface for all
      simulated cases, which is in agreement with other theoretical research and
      supports the experimental findings in the literature on the origins of cartilage
      damage. For articular cartilage layers of different thicknesses, the stresses in
      the thick layer were found to be higher than those in the thin layer. Compared to
      other models of joint contact, the present model offers more possibilities for
      investigating practical applications, such as simulating the effects associated
      with cartilage degeneration in diseases such as osteoarthritis, and comparing
      theoretical predictions with experimental measurements of pressure distribution
      and contact area in joints.

PMID- 8884473
TI  - Optimum phase ratio in the triple jump.
AB  - The purpose of this study was to develop and validate a method to determine the
      optimum phase ratio that yields the longest actual distance for a given triple
      jumper. Two hypotheses were tested: (a) for any given triple jumper, the greater
      the gain in the vertical velocity the greater the loss in the horizontal
      velocity; and (b) there is no single optimum phase ratio for all triple jumpers.
      Kinematic data were collected for four elite male triple jumpers. It was found
      that the loss in the horizontal velocity during a support phase has a significant
      positive linear correlation with the gain in the vertical velocity during the
      same support phase. The slope of the regression line was referred to as the
      horizontal-to-vertical velocity conversion factor. Based on this relationship, an
      optimization model for the longest actual distance was developed to determine the
      optimum phase ratio for each of the four subjects. The optimization results
      showed that there was an optimum phase ratio for the longest actual distance for
      each triple jumper. The results of a validity test showed that the model
      predicted the actual distance with a degree of fair accuracy. The results of
      sensitivity analysis showed that the optimum phase ratio for a given athlete was
      a function of the horizontal-to-vertical velocity conversion factor and the
      horizontal velocity at the touchdown of the hop. These results support the two
      hypotheses of this study.

PMID- 8884474
TI  - Maximal contraction lessens impact response in a muscle contusion model.
AB  - The effect of muscle contraction on a contusion injury model was studied in the
      gastrocnemius muscle of anesthetized rats. Both limbs of 18 rats received a
      contusion injury with a blunt non-penetrating impact. One hind limb was relaxed
      during impact and the other was electrically stimulated to tetanic contraction.
      The impact was produced using a drop-mass technique (mass = 171 g, height = 101
      cm, spherical radius of impactor tip = 6.4 mm). The impact response was
      determined by sampling (10 kHz) the transmitted impact force and the displacement
      of the impactor. In a subgroup of nine rats, the severity of the contusion injury
      was measured by recording contractile tension in twitch and tetanus within two
      hours of injury. We found that the peak impact force was significantly less (p <
      0.01), while the peak impact displacement was significantly greater (p < 0.01) in
      the contracted limb. Correspondingly, the impact stiffness of the contracted limb
      was significantly less (p < 0.01) than the impact stiffness in the relaxed limb.
      Both impacts produced significant injuries relative to an uninjured control
      group. The tetanic tension (31 +/- 4 N) generated by the muscles that were
      contracted during impact was significantly (p < 0.03) greater than that generated
      by the muscles that were relaxed during impact (27 +/- 4 N). The findings from
      this specific model indicate that the impact response of the limbs with relaxed
      muscle was dominated by the underlying bone, while maximally contracted muscle
      decreased the influence of the bone and lessened the impact response. Maximally
      contracted muscle was not more susceptible to injury and may act as protective
      mechanism against some impacts.

PMID- 8884475
TI  - Numerical study of wall mechanics and fluid dynamics in end-to-side anastomoses
      and correlation to intimal hyperplasia.
AB  - In order to analyse the wall mechanics and the flow dynamics in compliant
      vascular distal end-to-side anastomoses, computer simulation has been performed.
      In a model study the effect of compliance mismatch on the wall displacements and
      on the intramural stresses as well as the influence of wall distensibility on the
      flow patterns are demonstrated applying two distensible models with different
      graft elasticity. In addition, the flow in a rigid model simulating a vein graft
      without adaption of the venous lumen has been investigated. The geometries for
      these models were obtained from a concurrent experimental study, where the
      formation of distal anastomotic intimal hyperplasia (DAIH) was studied in
      untreated and externally stiffened autologous venous grafts in sheep. In the flow
      study the time-dependent, three-dimensional Navier-Stokes equations describing
      the motion of an incompressible Newtonian fluid are applied. The vessel wall is
      modelled using a geometrically non-linear shell structure. In an iteratively
      coupled approach the transient shell equations and the governing fluid equations
      are solved numerically using the finite element method. In both compliant models
      maximum displacement and areas of steep stress gradients are observed in the
      junction region along the graft-artery intersection. The comparison of the normal
      deformations and the distribution and magnitude of intramural stress shows
      quantitative differences. The graft elasticity acts as a regulating factor for
      the deformability and the stress concentration in the junction area: In the model
      with high graft-elasticity maximum normal deformation at the side wall is 17%.
      This is twice as large as in the stiff graft model and maximum principle stress
      at the inner surface differs by one order of magnitude. The numerical results
      concerning the flow patterns indicate strongly skewed axial velocity profiles
      downstream of the junction, large secondary motion, flow separation and
      recirculation on the artery floor opposite the junction and at the inner wall
      downstream of the toe. In these regions a correlation between the time-averaged
      fluid wall shear stress and intimal thickening found in the animal experiment can
      be observed, whereas the pronounced formation of DAIH at the suture line seems to
      be mainly dependent on wall mechanical factors such as intramural stress and
      strain.

PMID- 8884477
TI  - A dynamic model for simulating movements of the elbow, forearm, an wrist.
AB  - We developed a dynamic model of the upper extremity to simulate forearm and wrist
      movements. The model is based on the skeletal structure of the arm and is capable
      of elbow flexion/extension, forearm pronosupination, and wrist flexion/extension
      and radial/ulnar deviation movements. Movements are produced by activation of a
      Hill-type model of muscle, and limits on joint motion are imposed by passive
      moments modeled after experimental results. We investigated the muscle output
      force sensitivity, as well as wrist flexion/extension motion sensitivity to
      parameter variations. The tendon slack length and muscle fiber length were found
      to have the greatest influence on muscle output and flexion/extension wrist
      motion. The model captured the direction of the moment vectors at the wrist well,
      but predicted much higher moments than were measured by stimulating the paralyzed
      muscles of one tetraplegic subject.

PMID- 8884476
TI  - The dependence of shear failure properties of trabecular bone on apparent density
      and trabecular orientation.
AB  - The shear properties of trabecular bone, in particular the shear failure strains,
      are not well understood despite their potential importance in age-related
      fractures and prosthesis loosening. We hypothesized that shear failure strains
      (yield and ultimate) are independent of apparent density and trabecular
      orientation, i.e. are homogeneous and isotropic. We measured the shear failure
      properties of bovine tibial trabecular bone, where specimens were loaded to
      failure in torsion longitudinally (n = 25) or transversely (n = 23) relative to
      the primary trabecular orientation. We found that although failure stresses
      depended strongly on apparent density (r2 = 0.61 - 0.80), failure strains were
      independent of apparent density for both trabecular orientations. Although the
      mean (+/-S.D.) yield strain in the longitudinal group (1.46 +/- 0.19%) was 10%
      higher (p = 0.01) than in the transverse group (1.33 +/- 0.15%), indicating a
      slight anisotropy of shear yield strains, the mean ultimate strains did not
      depend on trabecular orientation (longitudinal group 4.60 +/- 0.77% vs transverse
      group 4.24 +/- 1.25%, p = 0.20). These findings indicate that shear failure
      strains are homogeneous and largely isotropic. By combining our shear data with
      compressive data from a previous experiment, we also predicted that trabecular
      bone can fail in shear when subjected to compressive loads that are not aligned
      with the principal trabecular orientation. If this prediction holds for human
      bone, shear may be a dominant failure mode during off-axis loading of trabecular
      bone in vivo, such as during falls on the hip.

PMID- 8884478
TI  - Poroelastic creep response analysis of a lumbar motion segment in compression.
AB  - The nonlinear three-dimensional poroelastic creep response of a lumbar motion
      segment under a constant axial compression (400, 1200, or 2000 N) is investigated
      for a period of 2 h. The role of facet joints, strain-dependent variable
      permeability, boundary pore pressure, and coupled sagittal rotation on response
      is studied. Biomechanics of annulus excision, nucleotomy, and facetectomy are
      also investigated. Both material and geometric nonlinearities are considered. The
      annulus bulk is modelled as a nonhomogeneous composite of collagenous fibers and
      annulus bulk. As time progresses, axial displacement increases, pore pressure
      decreases, annulus bulk undergoes larger compressive stresses, fiber layers
      become slack, and facets carry larger loads. Surgical alterations markedly soften
      the temporal response and increase facets forces. In contrast, the strain
      dependent variable permeability and boundary pore pressure stiffen the response
      and decrease forces on the facets. Changes in the nucleus fluid content, facet
      joints, boundary pore pressure, and disc permeability markedly influence the
      lumbar biomechanics.

PMID- 8884479
TI  - The control of non-twisting somersaults using configuration changes.
AB  - Theoretical analyses have shown that rotations of a rigid body about the
      principal axis corresponding to the intermediate principal moment of inertia are
      unstable. This poses a potential problem for gymnasts who perform double
      somersaults without twist in a layout configuration. A computer simulation model
      is used to investigate configurational strategies for controlling such movements.
      It is shown that the build up of twist is not reduced by abduction of the arms
      but can be controlled by adopting a configuration with sufficient body flexion.
      For somersaults with a straight body, control in the form of asymmetrical arm
      abduction accelerations, based upon twist angular velocity and angular
      acceleration, is capable of preventing a build up of twist providing that the
      feedback time delay is less than a quarter somersault.

PMID- 8884480
TI  - Muscle activity patterns altered during pedaling at different body orientations.
AB  - Gravity is a contributing force that is believed to influence strongly the
      control of limb movements since it affects sensory input and also contributes to
      task mechanics. By altering the relative contribution of gravitational force to
      the overall forces used to control pedaling at different body orientations, we
      tested the hypothesis that joint torque and muscle activation patterns would be
      modified to generate steady-state pedaling at altered body orientations. Eleven
      healthy subjects pedaled a modified ergometer at different body orientations
      (from horizontal to vertical), maintaining the same workload (80 J), cadence (60
      rpm), and hip and knee kinematics. Pedal reaction forces and crank and pedal
      kinematics were measured and used to calculate joint torques and angles. EMG was
      recorded from four muscles (tibialis anterior, triceps surae, rectus femoris,
      biceps femoris). Measures of muscle activation (joint torque and EMG activity)
      showed strong dependence on body orientation, indicating that muscle activity is
      not fixed and is modified in response to altered body orientation. Simulations
      confirmed that, while joint torque changes were not necessary to pedal at
      different body orientations, observed changes were necessary to maintain
      consistent crank angular velocity profiles. Dependence of muscle activity on body
      orientation may be due to neural integration of sensory information with an
      internal model that includes characteristics of the endpoint, to produce
      consistent pedaling trajectories. Thus, both sensory consequences and mechanical
      aspects of gravitational forces are important determinants of locomotor tasks
      such as pedaling.

PMID- 8884481
TI  - A combined robotic/universal force sensor approach to determine in situ forces of
      knee ligaments.
AB  - We developed a system that uses a 6-degree-of-freedom (6-DOF) robotic manipulator
      combined with a 6-DOF force-moment sensor and a control system. The system is
      used to find and record the passive knee flexion path for controlling the knee
      flexion positions. It is also used to strain a knee structure by finding a
      multiple-DOF path in response to specific joint loading, e.g. anterior-posterior
      tibial force application. It is additionally used to measure in-situ forces in
      ligaments by recording differences in forces and moments when repeating a
      prerecorded path, both before and after removal of the ligament of interest.
      Example applications are included in the study.

PMID- 8884482
TI  - Design and development of an electromechanical ultrasound probe holder for
      urodynamics testing.
AB  - A prevalent difficulty in urodynamics studies employing ultrasonography is
      associated with the manual application of the imaging transducer to the perineum.
      We have developed an electromechanically operated device for remote positioning
      of an ultra-sound probe during voiding studies of the lower urinary tract. The
      mechanical arm holds the probe inside a funnel that is mounted underneath a
      modified portable commode on which the patient is seated. External manually
      operated mechanical slides are used to translate the probe along the three
      primary axes for initial lateral and vertical positioning. Backwards/forwards and
      left/right pivoting of the transducer is then accomplished via linear stepper
      motors that are operated with a hand-held controller. A preliminary evaluation
      has shown that the device is easy to use, safe, and allows excellent
      visualization of the bladder outlet and proximal urethra in both male and female
      patients. The capability to remotely adjust the imaging angle allows the patient
      to void in a more private setting behind a drawn curtain, thereby minimizing the
      psychological distress associated with this test and facilitating the acquisition
      of more physiological test results.

PMID- 8884483
TI  - Moment arms and lengths of human upper limb muscles as functions of joint angles.
AB  - Modeling of musculoskeletal structures requires accurate data on anatomical
      parameters such as muscle lengths (MLs), moment arms (MAs) and those describing
      the upper limb position. Using a geometrical model of planar arm movements with
      three degrees of freedom, we present, in an analytical form, the available
      information on the relationship between MAs and MLs and joint angles for thirteen
      human upper limb muscles. The degrees of freedom included are shoulder
      flexion/extension, elbow flexion/extension, and either wrist flexion/extension
      (the forearm in supination) or radial/ulnar deviation (the forearm in mid
      pronation). Previously published MA/angle curves were approximated by
      polynomials. ML/angle curves were obtained by combining the constant values of
      MLs (defined by the distance between the origin and insertion points for a
      specific upper limb position) with a variable part obtained by multiplying the MA
      (joint radius) and the joint angle. The MAs of the prime wrist movers in
      radial/ulnar deviation were linear functions of the joint angle (R2 > or =
      0.9954), while quadratic polynomials accurately described their MAs during wrist
      flexion/extensions. The relationship between MAs and the elbow angle was
      described by 2nd, 3rd or 5th-order polynomials (R2 > or = 0.9904), with a lesser
      quality of fit for the anconeus (R2 = 0.9349). In the full range of angular
      displacements, the length of wrist, elbow and shoulder muscles can change by 8.5,
      55 and 200%, respectively.

PMID- 8884484
TI  - Maximum isometric moments generated by the wrist muscles in flexion-extension and
      radial-ulnar deviation.
AB  - Maximum isometric and passive moments about the wrist were measured for a range
      of flexion-extension and radial-ulnar deviation angles in 10 healthy adult males.
      Each subject was seated in a test apparatus with his shoulder abducted 90
      degrees, elbow flexed 90 degrees, and body and forearm constrained. Peak flexion
      moments ranged from 5.2 to 18.7 N m (mean = 12.2, SD = 3.7), while peak extension
      moments ranged from 3.4 to 9.4 N m (mean = 7.1, SD = 2.1). The average flexion
      moment peaked at 40 degrees of flexion, whereas the average extension moment was
      relatively constant from 30 degrees flexion to 70 degrees extension. Peak moments
      generated by the radial and ulnar deviators ranged from 7.9 to 15.3 N m (mean =
      11.0, SD = 2.0) and 5.9 to 11.9 N m (mean = 9.5, SD = 2.2), respectively. Passive
      moments in flexion-extension were near zero in the central 150 degrees of motion,
      but increased at the end of the range of motion. The average passive moment was
      0.5 N m in 90 degrees flexion and 1.2 N m in 90 degrees extension. Average
      passive moments about the radial-ulnar deviation axis were near zero with the
      wrist radially deviated and at neutral, but increased to 0.9 N m in full ulnar
      deviation.

PMID- 8884485
TI  - Two-phase model of blood flow through stenosed tubes in the presence of a
      peripheral layer: applications.
AB  - The effects of red cell concentration and the peripheral layer on blood flow
      characteristics due to the presence of a mild stenosis, are studied. It is shown
      that the magnitudes of the flow characteristics significantly increase with cell
      concentration and the peripheral layer causes marked reduction in the magnitudes
      of the flow characteristics. Physiological relevance and the influence of various
      parameters are discussed.

PMID- 8884486
TI  - On improving the accuracy of instrumented spatial linkage system.
AB  - Calibration is important for improving the accuracy of instrumented spatial
      linkage (ISL) in the application of biomechanical studies. The assumption of the
      linear performance of the potentiometer transducer has limited the improvement of
      the linkage accuracy. We present a non-linear numerical calibration procedure and
      double potentiometer design to improve the accuracy of ISL. Through the use of a
      three-degree-of-freedom linkage, the non-linear calibration procedure and the
      double potentiometer design were shown to be effective in reducing the ISL
      errors. The error, i.e. standard deviation for the angle decreased from +/-0.38
      degree to +/-0.12 degree while the same for the translation decreased from +/
      0.41 to +/-0.16 mm. A high-accuracy linkage system using low-cost potentiometers
      could be constructed by using our calibration method and double potentiometer
      design.

PMID- 8884487
TI  - Two-dimensional representation of three-dimensional pelvic motion during human
      walking: an example of how projections can be misleading.
AB  - We investigated the movements of skin markers located on the anterior and
      posterior surfaces of the pelvis during normal walking. Plots of the vertical
      versus horizontal displacements of the body-surface markers for a single gait
      cycle yield characteristic horizontal figure-of-eight patterns, often referred to
      as Lissajous figures. Some literature citations indicate that these figure-of
      eight plots represent movement of the body center of mass in the plane
      perpendicular to the line of progression. We show evidence suggesting that the
      Lissajous plot for the body center of mass is U-shaped and that the observed
      figure-of-eight pattern is due to the location of the marker on the body surface
      coupled with pelvic rotation. A simple rigid-body model is used to demonstrate
      that pelvic rotation about the vertical axis can appear as horizontal
      translations in a planar projection. Even small rotations about the vertical axis
      are observable in the phase relation between horizontal and vertical
      displacements of surface markers in the projection. As a result, Lissajous plots
      of vertical versus horizontal displacements, particularly for points on the
      exterior of a rigid body, may be strongly influenced by rotations. We demonstrate
      that Lissajous patterns for the model are similar to patterns for the human
      pelvis during walking and that pelvic rotation has a large influence on Lissajous
      patterns (vertical movement vs medial-lateral) plotted from pelvic marker data.
      This demonstration illustrates how two-dimensional representations of three
      dimensional movement can lead to incorrect interpretations.

PMID- 8884488
TI  - Posture prediction for static sagittal-plane lifting.
AB  - Three separate models are presented to predict the postures of humans performing
      static sagittal lifting tasks. The models use a common inverse-kinematics
      characterization to represent mathematically feasible postures, but explore
      different criteria functions for selecting a final posture. The first criterion
      assumes that subjects minimize the overall effort associated with a posture. The
      second criterion expresses effort locally as opposed to globally, and minimizes
      this value. The third criterion maximizes body stability. The postures predicted
      by these three models were compared to the postures assumed by 16 subjects
      performing 4 static sagittal lifting tasks. The results showed that all of the
      prediction errors were significantly greater than zero, but that the first
      objective function (minimum total torque) was more accurate than the other two
      criteria. The models were in general less accurate for postures that had lower
      hand positions than for those with higher hand positions.

PMID- 8884489
TI  - Bone bonding behavior of titanium and its alloys when coated with titanium oxide
      (TiO2) and titanium silicate (Ti5Si3).
AB  - It has been proposed that the essential requirement for artificial materials to
      bond to living bone is the formation of bonelike apatite on their surfaces in the
      body. Recent studies have shown that titanium hydrogel and silica gel induce
      apatite formation on their surface in a simulated body fluid. In this study, the
      influence of titanium oxide and titanium silicate on the bonding of titanium
      alloys to bone was studied. Rectangular implants (15 x 10 x 2.2 mm) of titanium,
      Ti-6Al-4V, Ti-6Al-2Nb-Ta, Ti-6Al-4V coated with TiO2, and Ti-6Al-4V coated with
      Ti5Si3 were implanted into the tibial metaphyses of mature rabbits. At 8 and 24
      weeks after implantation, the tibiae containing the implants were dissected out
      and subjected to a detaching testing. The failure load for titanium, Ti-6Al-4V,
      Ti-6Al-2Nb-Ta, Ti-6Al-4V coated with TiO2, and Ti-6Al-4V coated with Ti5Si3 were,
      respectively, 0.68 +/- 0.48, 0.22 +/- 0.46, 0.67 +/- 0.59, 2.18 +/- 0.71 and 2.03
      +/- 0.41 kgf at 8 weeks, and 2.7 +/- 0.91, 2.58 +/- 1.29, 2.38 +/- 0.41, 3.79 +/-
      1.7, and 2.79 +/- 0.87 kgf at 24 weeks after implantation. Histological
      examination by Giemsa surface staining, CMR, and SEM-EPMA revealed the coated
      titanium alloy implants directly bonded to bone tissue during early implantation.
      A Ca-P layer was observed at the interface of the coated implants and the bone.
      The results of this study indicated that TiO2 and Ti5Si3 can enhance the early
      bonding of titanium alloys to bone by inducing a Ca-P layer (chemical apatite) on
      the surface of titanium alloys. It also is suggested that the direct bone contact
      occurs in relation to the calcium and phosphorus adsorption onto the surface of
      the titanium passive layer formed during long-term implantation.

PMID- 8884490
TI  - Synthesis of phenylazido-derivatized substances and photochemical surface
      modification to immobilize functional groups.
AB  - Phenylazido-derivatized low-molecular-weight substances and copolymers containing
      hydrocarbon- or fluorocarbonalkyl group, sulfonato or amino group, and hydroxyl
      group were prepared. Upon coating and subsequent ultraviolet (UV) light
      irradiation, covalent fixation of these substances or copolymers took place only
      at irradiated portions of polymer surfaces, providing a hydrophobic, ionic, or
      hydrophilic nature. These were verified with electron spectroscopy for chemical
      analysis (ESCA) spectra and water contact-angle measurement. Endothelial cells
      adhered on photochemically modified surfaces which have alkyl, sulfonato, or
      amino groups on their surfaces, whereas little adhesion occurred on a hydroxyl
      group-bearing hydrogellike surface. When UV light was irradiated through a
      photomask on the polymer surfaces, patterned and microprocessed surfaces having
      cell-adhering and nonadhering regions were obtained. The potential application of
      this photochemical surface processing method in biomedical engineering is
      discussed.

PMID- 8884491
TI  - Control of cell adhesion, migration, and orientation on photochemically
      microprocessed surfaces.
AB  - Using surface-photochemistry-driven microprocessing, striped patterns of cell
      adhesive and nonadhesive domains were prepared on tissue-culture dishes. The
      width of striped patterns ranged from 20 to 130 microns. When endothelial cells
      were cultured on such dimensionally well-defined surfaces, cells adhered,
      migrated, and proliferated only on cell-adhesive domains. Migration potentials
      such as tracks of moving cells and migration rates were determined using a time
      lapse video recording apparatus under a phase-contrast microscope and a computer
      assisted image analyzer. The migration track in the direction of the width of the
      stripe-pattern was limited to the size of the width, and effective migratory
      distance over 400 min of observation was considerably reduced, to almost half
      that for a nontreated surface, whereas migratory rate was not changed by surface
      processing, irrespective of the stripe-pattern width. After a 2-day culture,
      oriented patterned cellular sheets were obtained. Cells were elongated and
      aligned along the axis of the striped pattern. The degrees of orientation and
      elongation were enhanced with a decrease of the line width. At the narrowest
      surface domain, cells only migrated back and forth, and eventually they became
      highly elongated and oriented along the axis of the domain. These results
      indicated that the adhesion area, migrating direction, and orientation of cells
      can be controlled by this method with micron-order precision. This method
      provides quantitative information on the kinetics of the migration process and
      the morphogenesis of the microprocessed surface.

PMID- 8884492
TI  - Evolution of the bone-titanium interface on implants coated/noncoated with
      xenogeneic bone particles: quantitative microscopic analysis.
AB  - Titanium cylinders having a sandblasted surface were implanted in holes drilled
      in the internal condyles of rabbit femurs. The right side received a titanium
      implant coated with xenogeneic bone particles and the left side received a
      titanium cylinder alone and was used as control. The femoral extremities were
      removed at 1, 2, and 3 months postsurgery and embedded undecalcified in
      methacrylic resins. Sections were studied by quantitative analysis and the
      interface contact between bone and titanium was measured at two microscopic
      magnifications due to the fractal dimension of this parameter. In addition the
      amount of bone volume in a given referent volume provided automatically by the
      image analyzer was obtained. No differences could be evidenced between the two
      series of implants, supporting the view that xenogeneic particles were
      ineffective in improving the attachment of bone to the implant. The bone-to
      implant interface measured at the low magnification reflected the anchorage of
      the implant. In both series a progressive increase upon time of the bone-to
      implant interface at the highest microscopic magnification evidenced the
      importance of late remodeling changes responsible for bone bonding and the
      fractal characteristics of this interface, related to surface quality of the
      implant responsible for stress transfer.

PMID- 8884493
TI  - Synthetic scleral reinforcement materials. II. Collagen types in the fibrous
      capsule.
AB  - Attainment of a steady state in fibrous-capsule formation around a polymeric
      implant is indicative of minimization of the foreign-body response, and is
      characterized by thin capsule walls, few macrophages, and the replacement of type
      III collagen with type I collagen within the capsular matrix. We implanted four
      general types of extraocular band materials (porous, solid, composite, and
      patched) in rabbit eyes, and examined the proportions of types III and I collagen
      in the surrounding fibrous-capsule walls at intervals after surgery.
      Immunohistochemical analysis showed that 18 months after implantation of the band
      materials, the capsules adjacent to the porous-material surfaces had virtually no
      type III collagen remaining, while the solid-surface-material capsules still
      contained more than trace amounts (greater than 5%). In that the bands were
      implanted around the outside of the globe, which provides a dynamic environment
      in constant motion, it may be that the cellular ingrowth permitted by the porous
      materials increased the stability of the implants, thereby lessening the foreign
      body response and allowing the collagen replacement characteristic of the steady
      state to be completed. In contrast the solid-surface implants, which had little
      cellular ingrowth, may have continued to undergo sufficient micromovement within
      the capsule walls to sustain a low-level activation of the wound-healing
      response, resulting in thicker capsule walls and residual type III collagen a
      year and a half after implantation surgery.

PMID- 8884494
TI  - Effect of the substitution of La2O3 for CaO on the bioactivity of 2.5CaO.2SiO2
      glass.
AB  - Glasses of the following composition were prepared: (2.5-x)CaO.x/3La2O3.2SiO2 (0
      < or = x < or = 1). Their behavior when soaked in a simulated body fluid (SBF)
      was studied by means of electron microscopy (EM) equipped with an energy
      dispersive system (EDS) for elemental analysis, IR spectroscopy, and x-ray
      diffraction. All the studied glasses react with SBF by forming a calcium
      phosphate layer. This layer appears to be increasingly thinner with increasing
      amounts of La2O3 substituted. The experimental results are in good agreement with
      mechanisms reported in the literature. Moreover they suggest that lanthanum oxide
      is retained in the layer below the phosphate. After 6 days of soaking,
      crystalline hydroxyapatite is formed in the case of La2O3 free glass.

PMID- 8884495
TI  - Preparation of purified atactic polypropylene and polyvinyl methyl ether surfaces
      for thrombogenicity studies.
AB  - Commercial samples of atactic polypropylene (aPP) and polyvinyl methyl ether
      (PVME) were purified and spin-cast onto glass coverslips with a view to using
      these as model surfaces in thrombogenicity studies. These materials differ from
      polyvinyl alcohol (PVA) in a single functional group and are similarly amorphous:
      with the same backbone they have a hydroxyl, a methoxy, or a methyl group. The
      objective was to understand the role of the hydroxyl group in the platelet
      reactivity of PVA. Surface characterization showed that they were chemically pure
      (as determined by X-ray photoelectron spectroscopy) but not smooth (as determined
      by scanning electron microscopy or interferometry), presumably due to the
      difficulties of spin-casting optically clear films from hot solutions (aPP or
      polyethylene [PE]) or because of imperfect adhesion to the saline-treated
      substrate (PVME). PVME was also gamma-irradiated to insolubilize it. Fewer
      platelets adhered to PVA than to PVME or to aPP and PE, but roughness effects and
      limited data preclude definitive conclusions regarding the effect of functional
      groups. Less protein was found on PVA than on the hydrophobic surfaces, but the
      significance of this observation is unclear. Further studies with more sensitive
      protocols are called for to examine the extent of platelet activation and its
      relationship to surface chemistry.

PMID- 8884496
TI  - Use of p-nitrophenyl chloroformate chemistry to immobilize protein on orthopedic
      biomaterials.
AB  - Biochemical surface modification involves covalently immobilizing biomolecules
      onto biomaterial surfaces to induce specific biological responses. This approach
      may be useful for enhancing the fixation of orthopedic implants. p-Nitrophenyl
      chloroformate (p-NPC) was used to immobilize protein on bulk samples of Co-Cr-Mo
      and Ti-6Al-4V. Activation of both materials was dependent on the concentration of
      p-NPC, with a maximum of approximately 1.5 active groups/nm2 of nominal surface
      area. Trypsin was used as a model protein because much is known about its
      structure and mode of action. Derivatization with 0.65 mg p-NPC/cm2 resulted in
      significantly greater enzymatic activity (7.4 BAEE [N-(alpha)-benzoyl-L-arginine
      ethyl ester hydrochloride] units) on the Co-Cr-Mo samples compared with higher
      concentrations of p-NPC (5 BAEE units) and with simple adsorption of trypsin (1.5
      BAEE units). An activity of 10.5 BAEE units was measured on both adsorbed and p
      NPC-activated Ti-6Al-4V, with the exception of samples derivatized with 1.95 mg p
      NPC/cm2, on which activity was significantly lower (4 BAEE units). In probing the
      linkages between trypsin and biomaterial by treatment with chaotropic agents,
      guanidine hydrochloride (GuHCl) was observed to eliminate more enzymatic activity
      than was urea. On Co-Cr-Mo samples, GuHCl removed nearly all the trypsin
      activity, while urea significantly decreased the activity only at a concentration
      of 0.65 mg p-NPC/cm2. Treatment of Ti-6Al-4V samples with GuHCl caused a trend of
      decreasing activity with increasing concentration of p-NPC, whereas urea had no
      effect on immobilized trypsin activity.

PMID- 8884497
TI  - Shrinkage temperature versus protein extraction as a measure of stabilization of
      photooxidized tissue.
AB  - A rise in thermal denaturation temperature has been utilized as an indication of
      stabilization of collagen-containing materials such as pericardial tissue and
      porcine heart-valve leaflets following treatment with glutaraldehyde, Denacol, or
      other chemical agents. In contrast, stabilization of bovine pericardial tissue by
      dye-mediated photooxidation does not result in a significant rise in shrinkage
      temperature comparable with these treated materials. It was therefore
      hypothesized that a rise in shrinkage temperature is not a necessary indication
      for tissue stabilization. A sensitive protein extraction assay has been developed
      which can be used to monitor the stabilization of pericardial tissue by a variety
      of treatment methods, including photooxidation. A reduction in extractable
      protein, as analyzed by polyacrylamide gel electrophoresis, is noted for
      pericardial tissue treated with photooxidation, glutaraldehyde, or Denacol. Loss
      of extractable protein, as a function of treatment time, correlates well with a
      significant rise in shrinkage temperature for pericardium treated with
      glutaraldehyde or Denacol but not with photooxidation. This difference is
      attributed to the stabilization processes of glutaraldehyde and Denacol, which
      involve extensive crosslinking and polymer formation within and in addition to
      the native pericardial matrix, leading to a rise in matrix complexity and thermal
      stability. In contrast, photooxidation is a catalytic process involving
      modification and crosslink formation within existing matrix components, resulting
      in a material with little added matrix complexity.

PMID- 8884498
TI  - Static and dynamic fatigue properties of carbon ligament prosthesis.
AB  - The aim of the present paper was to characterize the static and dynamic
      mechanical properties of carbon braids used in medicine as prostheses of
      ligaments and tendons. A computing system (PC software) was used to register and
      analyze the data of mechanical tests. Tensile static tests (creep testing) were
      utilized to determine the failure-free value of static force. Fatigue dynamic
      properties of carbon braids in tensile-tensile cyclic tests including the effect
      of simulated body conditions were analyzed. The braids were immersed in isotonic
      solution at 37 degrees C. Fatigue life was markedly lowered in air in comparison
      with simulated body conditions. For a given value of maximum cyclic force,
      decreasing the minimum/maximum force ratio decreased the number of cycles to
      failure. The mechanical approach of fatigue behavior based on approximately
      maximum fatigue force and number of cycles to failure by analytical expression
      was given. Energy dissipation due to the hysteresis loop was considered.

PMID- 8884499
TI  - Effect of physical crosslinking methods on collagen-fiber durability in
      proteolytic solutions.
AB  - We previously demonstrated that ultraviolet (UV) or dehydrothermal (DHT)
      crosslinking partially denatured fibers extruded from an insoluble type I
      collagen dispersion. In this study denaturation effects were evaluated by
      measuring collagen-fiber sensitivity to trypsin. Shrinkage-temperature
      measurements and sensitivity to collagenase served as indices of crosslinking. UV
      or DHT crosslinking increased the collagen-fiber shrinkage temperature,
      resistance to degradation in collagenase, and durability under load in
      collagenase. However, in trypsin solutions, solubility was significantly
      increased for UV (approximately 11%) or DHT (approximately 15%) crosslinked
      fibers compared with uncrosslinked fibers (approximately 4%). Size-exclusion
      chromatography indicated that no intact collagen alpha-chains were present in the
      soluble fraction of fibers exposed to trypsin (MW < 1 kD). Interestingly, UV
      crosslinked collagen fibers remained intact an order of magnitude longer (4840 +/
      739 min) than DHT-crosslinked (473 +/- 39 min) or uncrosslinked (108 +/- 53 min)
      fibers when placed under load in trypsin solutions. These data indicate that
      mechanical loading during incubation in a trypsin solution measures denaturation
      effects not detected by the trypsin-solubility assay. Our results suggest that
      DHT-crosslinked collagen fibers should not be used as load-bearing implants. UV
      crosslinked fibers may retain more native structure and should exhibit greater
      resistance to nonspecific proteases in vivo.

PMID- 8884500
TI  - Sterility, mechanical properties, and molecular stability of polylactide internal
      fixation devices treated with low-temperature plasmas.
AB  - The effect of low-temperature plasma on sterility, molecular, mechanical, and
      crystalline properties of poly (L-lactide), poly (L/D-lactide) and poly (L/DL
      lactide) was investigated. Polymers were treated for 15 and 30 min at 100 W with
      nitrogen, argon, oxygen, and carbon dioxide plasma. All polymers treated with
      oxygen or carbon dioxide plasma were rendered sterile after 15 min of treatment.
      Only 70% of the samples treated under similar conditions with nitrogen or argon
      plasma were sterile. Extension of the exposure time to 30 min and increasing
      power to 200 W did not improve sterilization efficiency. Plasma sterilization,
      under the conditions used, caused no significant decrease or increase in overall
      molecular weight or polydispersity of the polylactides used. In most instances
      the effect of plasma sterilization was to slightly increase the overall molecular
      weight of the polymers studied. Treatment with argon plasma led to a more
      consistent increase in molecular weight than did treatment with nitrogen, oxygen,
      or carbon dioxide. Analysis of the surface (skin) of a poly(L-lactide) injection
      molded rod following plasma sterilization indicated an increase in molecular
      weight as related to the interior (core) of the rod. Comparison of Mark-Houwink
      plots for the surface and interior of poly(L-lactide) injection-molded rods
      following plasma sterilization indicated an increase in chain branching for the
      surface relative to the interior of the rod. Generally the highly crystalline
      poly(L-lactide) was less susceptible to change upon plasma treatment than was the
      less crystalline poly(L/D-lactide) and poly(L/DL-lactide). The mechanical
      properties (shear strength, bending strength, and moduli) of the polylactides
      were not affected by plasma treatment. The overall melting temperature and the
      heat of melting of polylactides studied were not affected by plasma treatment.
      The melting temperature of the skin of the samples was about 1 degree C higher
      than the melting temperature of the core due to the chain orientation upon
      injection-molding. Plasma treatment of the polylactides reduced the melting
      temperature of the skin by 3 degrees C to 5 degrees C due to the crosslinking or
      branching at the surface layer.

PMID- 8884501
TI  - Platelet adhesion to novel phospholipid materials: modified phosphatidylcholine
      covalently immobilized to silica, polypropylene, and PTFE materials.
AB  - Based on the premise of achieving blood compatibility through mimicking the
      chemical constitutents of the biologically insert surface of the unactivated
      platelet membrane, a process was developed that entails the covalent grafting of
      modified phosphatidylcholine molecules to materials including silica,
      polypropylene, and polytetrafluoroethylene (PTFE) polymer films. These materials
      were characterized using x-ray photoelectron spectroscopy (XPS) and contactangle
      measurements. The phosphatidylcholine-containing materials (PC materials) were
      used as substrates in the plateletadhesion assays and were subjected to enzymatic
      degradation evaluation. Phosphatidylcholine-grafted silica materials do not
      support platelet adhesion. In addition the number of adherent platelets correlate
      with the amount of grafted phospholipid present, as indicated by the phosphorus/
      carbon ratio obtained by XPS analysis. Platelet adhesion to phosphatidylcholine
      grafted polypropylene and PTFE was inhibited 80% and 90%, respectively, when
      compared with platelet adhesion to unmodified polypropylene and PTFE.

PMID- 8884502
TI  - Biocompatibility testing of NiTi screws using immunohistochemistry on sections
      containing metallic implants.
AB  - NiTi is one of the most innovative concepts to have appeared in the field of
      metallic biomaterials in recent years but its biocompatibility remains
      controversial. We evaluated the biocompatibility of Nitinol screws using
      immunohistochemistry to observe the distribution of bone proteins during bone
      remodeling process around NiTi implant. Results were compared with screws made of
      Vitallium, c.p. titanium, Duplex austenitic-ferritic stainless steel (SAF), and
      Stainless Steel 316L. Screws were implanted in rabbit tibia for 3, 6, and 12
      weeks. Embedding was performed in the hard resin Technovit, and for the
      immunohistochemical procedure undecalcified sections with bone-anchored implants
      could thus be used. The immunostaining method developed seemed to be a reliable
      technique to stain proteins in undecalcified sections. Biocompatibility results
      of the NiTi screws compared with the other screws showed a slower osteogenesis
      process characterized by no close contact between implant and bone, disorganized
      migration of osteoblasts around the implant, and a lower activity of osteonectin
      synthesis.

PMID- 8884503
TI  - Platelet interaction with pyrolytic carbon heart-valve leaflets.
AB  - Although the newest generation of mechanical heart-valve prosthetics constructed
      either partially or wholly of lowtemperature isotropic pyrolytic carbon (LTIC)
      have significantly reduced thromboembolic complications compared with early
      generation mechanical valves (e.g., Starr-Edwards), thromboembolism remains an
      important clinical complication. In the present study, high-resolution,
      lowvoltage scanning electron microscopy (HR-LV-SEM) was used to examine the
      structure and platelet interaction properties of LTIC valve leaflets manufactured
      by both Carbo Medics, Inc. and by St. Jude Medical, Inc. Valve leaflets from both
      manufacturers, prepared and polished exactly as used in clinical heart valves,
      had similar surface energetics and elemental composition. Examination with LV-SEM
      revealed a rough and complex three-dimensional surface structure with nanometer-
      to micron-size features. In vitro adhesion of human platelets on the LTIC
      materials and Formvar were evaluated in the presence of 1 mg/mL albumin. Platelet
      surface activation, as evaluated by shape change, spread area, and deposition,
      was extremely extensive on the LTIC materials compared with the Formvar positive
      control material. LTIC-adherent platelets were extremely thin, and closely
      followed the rough LTIC contours, greatly limiting their visibility with
      conventional SEM. These observations demonstrate that LTIC surfaces can
      extensively activate platelets even in the presence of albumin, thereby
      suggesting that platelet interactions with pyrolytic carbon may have a
      significant role in mechanical-valve thromboembolism.

PMID- 8884504
TI  - In vitro characterization of a fluoropassivated gelatin-impregnated polyester
      mesh for hernia repair.
AB  - The surgical management of abdominal hernias requires prosthetic grafting in
      situations where the defect is too large or the surrounding tissue is not
      available for repair. Flat patches made of different biomaterials have been used
      in textile or microporous forms. The present work describes the results of an in
      vitro study comparing the morphological, mechanical, and chemical characteristics
      of a new textile prototype, Fluoropassiv, made of polyester fibers treated with a
      fluoropolymer and impregnated with gelatin to those of seven existing commercial
      meshes and patches made from polypropylene, polyester, polytetrafluoroethylene
      (PTFE) yarns, and expanded microporous PTFE graft. The morphological study
      revealed a diversity of structures having a minimal relative porosity of 70%,
      high bursting, and suture retention strengths in comparison with natural muscular
      tissue. Elasticmoduli proved to depend more on the direction of the textile the
      rigidity was higher for those materials having tight structure, like the
      Fluoropassiv and the Surgipro meshes (> 30 MPa), whereas those with more open
      structures, such as the Marlex, Trelex, Lars, Bard Teflon, and GoreTex
      structures, showed lower elastic modulus (10 mPa). In addition, chemical analyses
      confirmed no irregularities in the polymers used in all prostheses and
      demonstrated that the fluoropolymer coating of the Fluoropassiv was uniformly
      distributed. The innovative aspects in the construction of the knitted fabric
      Fluoropassiv appears to make it suitable for repairing hernias, and the inclusion
      of both continuous fluoropolymer surface treatment of polyester fibers and
      gelatin impregnation appears to improve the healing process.

PMID- 8884505
TI  - Measurement of bacterial growth rates on polymers.
AB  - A video microscope system and a mathematical model were developed to observe and
      model the early stage of bacterial growth on polymer surfaces. Glass slides were
      coated with polyorthoester, poly(L-lactic acid), and polysulfone, and inserted
      into a laminar flow cell to expose them to bacterial cultures of Staphylococcus
      epidermidis, Pseudomonas aeruginosa, or Escherichia coli. The free energy of
      adhesion (delta Fadh) was determined from contact-angle measurements. The
      microscopic observations along with the mathematical model allowed measurement of
      the rates of adhesion, release, and growth. The growth rate of P. aeruginosa on
      the various surfaces correlated to the delta Fadh. The growth rates of all
      species on all of the surfaces were slower than the growth rates of the bacteria
      in suspension. The mathematical model is valid for early growth before the
      bacteria form a complete monolayer, and is useful in predicting and modeling
      early growth of bacteria on implanted biomaterials.

PMID- 8884506
TI  - Distribution of nickel and cobalt following dermal and systemic administration
      with in vitro and in vivo studies.
AB  - Contact dermatitis following skin contact with ionic metals occurs in about 15%
      of the human population, but systemic responses are not as common. It is
      generally believed that skin contact with metal ions leads to different
      biological processing compared with systemic contact. The purpose of the
      experiments presented here was to examine elimination of nickel and cobalt salts
      following skin application and following injection into the deep tissue of
      hamsters. In addition uptake of the metal by fibroblasts and by keratinocytes was
      examined in vitro. The data indicate that elimination of nickel and cobalt in the
      urine following systemic injection was rapid, as expected, but that elimination
      following skin application was delayed. Much of the metal was retained in the
      skin. Uptake of the metal by keratinocytes at low doses was greater than the
      uptake by the fibroblasts. At high doses the differences were not as great. Thus
      the conclusion is drawn that metal salts are retained in the skin for an extended
      period of time and could lead to prolonged antigen processing and consequent
      immune responses in the dermal tissue. Skin application leads to some systemic
      distribution but the systemic application did not lead to skin accumulation.

PMID- 8884507
TI  - Bilateral symmetry of biomechanical properties in rat femora.
AB  - In many studies, bone healing and remodeling have been examined in various animal
      models using one femur as a control for the contralateral femur based on the
      assumption that they are bilaterally symmetrical. Symmetry studies have been
      limited mainly to geometrical properties. The purpose of this study was to
      determine whether or not there is symmetry in the mechanical properties of rat
      femora. Two strain gauges were attached to the anterior surface parallel to the
      long axis of explanted femora of retired female breeder and 120-day-old male
      Sprague Dawley rats. Femora were mechanically tested in cantilever bending and
      the strain values were recorded. Moments of inertia, cortical areas, and moduli
      of elasticity were determined from strains and cross-sectional properties. Female
      femora showed a bilateral strain difference of less than 2.2% and an elastic
      modulus difference of less than 8.7%. Males had less than 2.0% and 7.9%
      differences for strain and elastic moduli, respectively. Statistical analysis
      showed no significant difference between left and right femoral strain values for
      the females, but modulus differences were significant different at the p = 0.05
      level. There was no significant difference in strain and modulus values for the
      males, indicating mechanical and geometrical symmetry of their femora.

PMID- 8884508
TI  - Randomized comparison of two techniques for titrating power during radiofrequency
      ablation of accessory pathways.
AB  - INTRODUCTION: The purpose of this study was to prospectively compare the value of
      impedance and temperature monitoring during accessory pathway ablation.
      Temperature and impedance monitoring can be used during radiofrequency ablation
      of accessory pathways to titrate power to achieve adequate but not excessive
      tissue heating. METHODS AND RESULTS: One hundred thirty-two patients with a
      single accessory pathway were randomly assigned to undergo ablation using either
      impedance monitoring or temperature monitoring. During impedance monitoring, the
      endpoint for titration of power was a 5- to 10-omega decrease in the measured
      impedance while for temperature monitoring the endpoint was to achieve a
      temperature of 58 degrees to 62 degrees C. Two protocols were used. In protocol 1
      (90 patients), impedance monitoring was performed with a nonthermistor catheter
      and temperature monitoring was performed with a thermistor catheter. In protocol
      2 (42 patients), a thermistor catheter was used in all patients. In protocol 1,
      the success rate (93% vs 93%; P = 1.0), ablation procedure duration (57 +/- 56 vs
      41 +/- 41 min), fluoroscopy time (48 +/- 29 vs 41 +/- 23 min; P = 0.3), number of
      applications (6.2 +/- 4.7 vs 5.7 +/- 4.6; P = 0.8), and the number of
      applications associated with coagulum formation (0.1 +/- 0.3 vs 0.3 +/- 0.6; P =
      0.1) were similar in the two groups. In protocol 2, as in protocol 1, there were
      no differences in the success rate (91% vs 95%; P = 1.0), ablation procedure
      duration (49 +/- 37 vs 62 +/- 55 min; P = 0.4), fluoroscopy time (46 +/- 24 vs 49
      +/- 36 min; P = 0.8), number of applications (6.8 +/- 7.0 vs 7.8 +/- 12.1; P =
      0.7), or number of applications associated with coagulum formation (0.3 +/- 0.6
      vs 0.2 +/- 0.7; P = 0.6), between the impedance and temperature monitoring
      groups. CONCLUSION: Temperature and impedance monitoring are equally effective in
      optimizing the results of accessory pathway ablation.

PMID- 8884509
TI  - Changes in plasma epinephrine concentration and in heart rate during head-up tilt
      testing in patients with neurocardiogenic syncope: correlation with successful
      therapy with beta-receptor antagonists.
AB  - INTRODUCTION: Tilt table testing is widely used in the management of patients
      with neurocardiogenic syncope. However, the exact pathophysiologic mechanism of
      this disorder is still under debate. Likewise, therapy of these patients
      continues to represent a challenge in many cases. Therefore, the present study
      aimed to gain further insight into the pathophysiology of this syndrome and to
      examine easily accessible clinical parameters that can improve therapy selection.
      METHODS AND RESULTS: In 16 patients with neurocardiogenic syncope, changes in
      endogenous catecholamine concentrations were determined during repeated tilt
      table testing before and during treatment with metoprolol. Tachycardia preceded
      syncope in 8 of 10 responders compared to only 1 of 6 nonresponders (P < 0.05).
      In responders, the relative increase in epinephrine levels averaged 197% +/- 51%
      during drug-free tilting and 75% +/- 33% during repeated testing while on beta
      blocker therapy (P < 0.05). In nonresponders, there was a smaller relative
      increase in epinephrine averaging 137% +/- 35% at baseline tilt. During repeated
      tilt testing, a similar increase was observed in these patients with recurrent
      syncope (156% +/- 104%; P = NS compared to baseline). CONCLUSION: In patients
      with neurocardiogenic syncope who show both an increase in epinephrine
      concentration during tilt test and sinus tachycardia prior to the onset of
      symptoms, beta-blocker treatment is very effective. These findings confirm the
      major role of sympathetic activation as a trigger of syncope. Particularly, heart
      rate changes at the onset of syncope may allow early identification of patients
      responding to antiadrenergic therapy.

PMID- 8884510
TI  - Electrophysiologic effects of the new class III antiarrhythmic drug dofetilide
      compared to the class IA antiarrhythmic drug quinidine in experimental canine
      atrial flutter: role of dispersion of refractoriness in antiarrhythmic efficacy.
AB  - INTRODUCTION: Previous studies suggest that class III antiarrhythmic drugs are
      more effective in reentrant arrhythmias because they prolong refractoriness (ERP)
      and wavelength and reduce dispersion of refractoriness compared to Class IA
      antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their
      effects on refractoriness. METHODS AND RESULTS: To test this hypothesis, the
      Class III drug dofetilide and the Class IA drug quinidine were studied in the
      experimental canine crush-injury model of atrial flutter, utilizing right atrial
      multipoint programmed stimulation and activation mapping. In seven dogs
      dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P <
      0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength
      by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and
      adjacent electrodes with ERP difference > or = 20 msec by 76% (P < 0.001).
      Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and
      suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P <
      0.001), slowed CV by 14% at 200-msec length cycle (P < 0.001) and by 19% at 150
      msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine
      did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by
      57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of
      dofetilide was greater than quinidine (P = 0.026) and correlated with reduced
      dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP
      difference > or = 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r =
      0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar
      mechanisms. Myocardial fiber orientation was nonuniform around the crush injury.
      CONCLUSIONS: Antiarrhythmic efficacy of dofetilide was greater than that of
      quinidine and correlated with drug-induced prolongation of wavelength and
      reduction in dispersion of refractoriness, effects produced only by dofetilide.

PMID- 8884511
TI  - Dofetilide versus quinidine for atrial flutter: viva la difference!?
AB  - Dofetilide is more effective than quinidine to terminate atrial flutter in this
      animal model. It is also more capable of lengthening refractoriness more
      uniformly than quinidine. While the investigators describe local changes in
      refractoriness and dispersion of refractoriness and wavelength meticulously, it
      is not clear which, if any, of these properties cause flutter termination or
      influence reinduction. This report provides new insight into the
      electrophysiologic mechanisms of antiarrhythmic drugs used to treat atrial
      arrhythmias. Related investigations are needed to expand our knowledge of the
      actions of antiarrhythmic drugs, how these drugs affect critical portions of the
      reentrant circuit, and how to identify potential adverse effects of these agents.
      Application of these data may help guide the use of antiarrhythmic drugs and
      allow development of safer, and yet more potent, compounds. At least, it will
      give us pause about using more toxic and less effective drugs. While Class III
      drugs, specifically dofetilide, may be more potent and beneficial than quinidine
      in this model, it is uncertain that these results pertain to human reentrant
      atrial arrhythmias, particularly, atrial flutter. Perhaps dofetilide will be
      effective for certain types of atrial flutter requiring an anatomical center
      defined by an area of injury or surgical scar in the right atrium. The fact that
      these, and previous, data indicate a specific beneficial effect of dofetilide,
      particularly on atrial flutter, is interesting. Even if dofetilide proves highly
      effective for human atrial flutter, its safety will need to be proven in large
      clinical trials. The most obvious concern about dofetilide is development of
      serious side effects such as torsades de pointes. Clinical trials of this drug
      for atrial arrhythmias are presently ongoing. Ultimately, the long-term use of
      such a drug is dependent on the emergence of other highly effective therapies
      such as radiofrequency ablation.

PMID- 8884512
TI  - Unequal atrial stretch in dogs increases dispersion of refractoriness conducive
      to developing atrial fibrillation.
AB  - INTRODUCTION: We have shown previously that acute atrial dilation prolonged
      atrial refractoriness. We hypothesized that this increase in refractoriness might
      be heterogeneous and could create an electrophysiologic substrate leading to
      atrial fibrillation. The purpose of the present study was to test that
      hypothesis. METHODS AND RESULTS: We studied 23 anesthetized open chest dogs.
      Bipolar plunge electrodes were placed in the medial free wall of the right atrium
      (thin region) and in the lower crista terminalis of the right atrium (thick
      region). Two bipolar plunge electrodes were also placed in the left ventricular
      apex to stimulate and record. Atrial effective refractory period (ERP) was
      measured in a group of nine dogs using the atrial extrastimulus method (A1A2) in
      two ways: during atrial pacing (AP) and during simultaneous atrioventricular (AV)
      pacing that achieved and AV interval of 0 msec (AV = 0). One liter/hour of normal
      saline was infused intravenously to elevate right atrial pressure and produce
      right atrial stretch. Atrial ERPs were measured before and after the normal
      saline infusion. To compare the extent of atrial stretch produced by volume
      overload, two pairs of sonomicrometer transducers were implanted in the thick and
      thin regions in a separate group of six dogs. The area encompassed by
      sonomicrometers was measured before and after saline infusion. The inducibility
      of atrial fibrillation was compared before and after saline infusion using rapid
      AP in another group of five dogs. Atrial pressure during sinus rhythm increased
      from 5.1 +/- 0.96 mmHg to 6.3 +/- 0.93 mmHg after normal saline infusion (P <
      0.01). ERP increased in the thin free wall from 151 +/- 14.3 to 172 +/- 14.7 msec
      (AV = 0), and from 169 +/- 12.0 to 170 +/- 14.3 msec (AP). ERP increased in the
      thick crista terminalis from 134 +/- 9.9 to 147 +/- 10.2 msec (AV = 0), and from
      133 +/- 7.9 to 146 +/- 9.8 msec (AV) (P < 0.01). The increase in ERP in the thin
      free wall exceeded that in the thick crista terminalis (P < 0.01), increasing the
      dispersion of atrial ERP. After 500-mL saline infusion for 30 minutes, the
      increase of area in the thin region was 12.8% +/- 3.7%, and that in the thick was
      3.5% +/- 3.2%. The increase of the area in the thin region after 1000 mL for 1
      hour was 18.8% +/- 6.2%, and that in the thick region was 6.3 +/- 5.1% (P <
      0.01). Atrial fibrillation was not induced in any dog before infusion, but
      induced in all five dogs after saline infusion. CONCLUSIONS: Atrial ERP in the
      thin right atrial free wall exceeds the ERP of the thick crista terminalis, and
      an increase in atrial pressure produced by saline infusion exaggerates this
      difference by stretching thin segments of the atrial myocardium more than it
      stretches thick regions. Thus, atrial stretch, by increasing the dispersion of
      atrial ERP, may be conducive to the development of atrial fibrillation.

PMID- 8884513
TI  - AV nodal function during atrial fibrillation: the role of electrotonic modulation
      of propagation.
AB  - The irregular ventricular rhythm that accompanies atrial fibrillation (AF) has
      been explained in terms of concealed conduction within the AV node (AVN).
      However, the cellular basis of concealed conduction in AF remains poorly
      understood. Our hypothesis is that electrotonic modulation of AVN propagation by
      atrial impulses blocked repetitively within the AVN is responsible for changes in
      function that lead to irregular ventricular rhythms in patients with AF. We have
      tested this idea using two different simplified computer ionic models of the AVN.
      The first ("black-box") model consisted of three cells: one representing the
      atrium, another one representing the AVN, and a third one representing the
      ventricle. The black-box model was used to establish the rules of behavior and
      predictions to be tested in a second, more elaborate model of the AVN. The latter
      ("nine-cell" model) incorporated a linear array of nine cells separated into
      three different regions. The first region of two cells represented the atrium;
      the second region of five cells represented the AV node; and the third region of
      two cells represented the ventricle. Cells were connected by appropriate coupling
      resistances. During regular atrial pacing, both models reproduced very closely
      the frequency dependence of AV conduction and refractoriness seen in patients and
      experimental animals. In addition, atrial impulses blocked within the AV node led
      to electrotonic inhibition or facilitation of propagation of immediately
      succeeding impulses. During simulated AF, using the nine-cell model, random
      variations in the atrial (A-A) interval yielded variations in the ventricular (V
      V) interval but there was no scaling, i.e., the V-V intervals were not multiples
      of the A-A intervals. As such, the model simulated the statistical behavior of
      the ventricles in patients with AF, including: (1) the ventricular rhythm was
      random; and (2) the coefficient of variation (standard deviation/mean) of the
      ventricular rhythm was relatively constant at any given mean V-V interval.
      Analysis of cell responses revealed that repetitive atrial input at random A-A
      intervals resulted in complex patterns of concealment within the AVN cells.
      Consequently, the effects of electrotonic modulation were also random, which
      resulted in a smearing of the AV conduction curve over A-A intervals that were
      larger than those predicted for 1:1 AV conduction. Hence, during AF, electrotonic
      modulation acts in concert with the frequency dependence of AVN conduction to
      result in complex patterns of ventricular activation. Finally, similarly to what
      was shown in patients, VVI pacing of the ventricle in the nine-cell model at the
      appropriate frequency led to blockade of nearly all anterograde (i.e., A-V)
      impulses. The essential feature here was that the retrograde impulse invading the
      AVN cells was followed by refractoriness with slow recovery of excitability,
      setting the stage for electrotonic inhibition of anterograde impulses. Overall,
      the results provide insight into the cellular mechanisms underlying AVN function
      and irregular ventricular response during AF.

PMID- 8884514
TI  - Cure of incessant pacemaker circus movement tachycardia by radiofrequency
      catheter ablation.
AB  - INTRODUCTION: Treatment of pacemaker circus movement tachycardia (PCMT) in
      patients with very long VA conduction times may present a problem. METHODS AND
      RESULTS: PCMT occurred in a 46-year-old woman with an uncommon AV nodal reentrant
      tachycardia who developed 2:1 AV block after fast pathway radiofrequency catheter
      (RF) ablation performed at another institution. Due to the long VA conduction
      time, PCMT could not be prevented by reprogramming the pacemaker or by the
      addition of antiarrhythmic drugs. Cure of the PCMT was obtained after selective
      RF ablation of the slow AV nodal pathway. CONCLUSION: RF ablation of the
      retrograde conduction offers another alternative for treatment of PCMT.

PMID- 8884515
TI  - Regional entrainment of atrial fibrillation in man.
AB  - INTRODUCTION: The feasibility of entrainment of macroreentrant atrial arrhythmias
      such as atrial flutter is well documented. Recently, it has been shown that
      regional entrainment of atrial fibrillation is feasible in dogs. METHODS AND
      RESULTS: Three patients with chronic atrial fibrillation underwent
      electrophysiologic evaluation with attempted entrainment of atrial fibrillation
      prior to successful endocardial atrial defibrillation. A 16-pole catheter was
      positioned in the trabeculated right atrium, and in two patients a multipolar
      catheter was positioned along the septum. In addition, two large surface area
      defibrillation catheters were placed, one in the lateral right atrium and one in
      the coronary sinus. Regional entrainment was attempted in the right atrium and
      from the catheter in the coronary sinus. Entrainment was achieved in the right
      atrium in all three patients over a cycle length range of 28, 17, and 13 msec,
      respectively, and over a radius of atrial tissue of at least 2.8 cm. Regional
      entrainment was demonstrated from the coronary sinus in one patient during
      simultaneous right atrial entrainment. Termination of atrial fibrillation during
      entrainment was not observed. CONCLUSION: Regional entrainment of chronic atrial
      fibrillation is feasible in humans.

PMID- 8884516
TI  - Insights into the electrophysiology of accessory pathway-mediated arrhythmias
      provided by the catheter ablation experience: "learning while burning, part III".
AB  - The success of catheter ablation has greatly improved the care of patients with
      paroxysmal tachycardias and has caused a revolution in the practice of
      electrophysiology. Some investigators have expressed that concern over procedural
      success in an increasingly interventional specialty threatens to eclipse attempts
      to understand the physiology of arrhythmia syndromes. Alternatively, due to the
      precise and directed nature of the lesions created with radiofrequency energy,
      catheter ablation procedures have allowed investigation to continue at a more
      focused level. In this article, the insights provided by the catheter ablation
      experience into the physiology of arrhythmias mediated by accessory AV pathways
      will be reviewed. Although the learning process was sometimes delayed by the
      nearly immediate success of radiofrequency catheter ablation, difficult
      situations have continued to renew efforts for understanding at a deeper level.
      Conscious attempts at "learning while burning" will provide the opportunity to
      investigate aspects of bypass tract physiology that remain incompletely
      characterized, such as partial response to therapy and late recurrence.

PMID- 8884517
TI  - Spontaneous termination of a tachycardia: what is the tachycardia mechanism?--VI.

PMID- 8884518
TI  - Ultrasound anatomy of the normal male reproductive tract.
AB  - Ultrasound is being used with increasing frequency in the evaluation of the male
      reproductive tract. To detect abnormalities, it is important to have a
      comprehensive understanding of the normal anatomy and normal variations. In this
      article, the ultrasound anatomy of the scrotum, penis, prostate, and seminal
      vesicles is presented. Because ultrasound is a very visual process, the anatomy
      is presented not only with text, but also through the liberal use of ultrasound
      images and associated diagrams. Ultrasound is both an operator- and equipment
      dependent procedure and, where appropriate, we have included technical
      discussions regarding ultrasound equipment and settings.

PMID- 8884519
TI  - Ultrasound in the assessment of the acute scrotum.
AB  - Color Doppler imaging (CDI) has become the study of choice in evaluation of the
      scrotum due to technological advances resulting in superior resolution and
      sensitive Doppler systems. CDI has become particularly helpful in evaluating the
      scrotum in the setting of acute disorders, such as torsion of the spermatic cord,
      epididymal and testicular inflammation, and scrotal trauma. CDI should be the
      study of choice to evaluate for torsion of the spermatic cord and demonstrates a
      high degree of accuracy. CDI in such a setting, however, does require operator
      experience, sensitive Doppler ultrasound equipment, and operator knowledge of the
      limitations of CDI. With epididymitis or epididymo-orchitis, CDI has proven to be
      quite helpful in evaluating the scrotal contents for the presence of inflammation
      and associated complications. In scrotal trauma, CDI's utility remains somewhat
      controversial, but with further investigation its appropriate application in this
      situation may become clear.

PMID- 8884520
TI  - Ultrasound assessment of testicular and paratesticular masses.
AB  - This article discusses the role of ultrasound in the workup of patients with
      suspected or palpable scrotal masses. By characterizing masses as intra- or
      extratesticular, the differential diagnosis can be narrowed considerably.
      Neoplasm is the primary concern with intratesticular masses, although non
      neoplastic conditions, such as hematoma and focal orchitis, may have a similar
      appearance. Correlation with the patient's history is essential. The sonographic
      presentation of extratesticular pathology, including varicocele and masses of
      epididymal origin, is also described.

PMID- 8884521
TI  - Role of ultrasound in the assessment of male infertility.
AB  - The use of ultrasonography has become an important component in the evaluation
      and treatment of male reproductive tract disorders. From the use of color flow
      Doppler ultrasonography for the assessment of varicoceles to transrectal
      ultrasonography combined with seminal vesiculography for the evaluation of
      ejaculatory duct obstruction, ultrasonography has practical clinical
      applications. In this article, the authors review the indications and use of
      ultrasonography in the assessment and treatment of the infertile male. The recent
      advances in diagnostic transrectal ultrasonography for ejaculatory duct
      obstruction, in particular, are emphasized.

PMID- 8884522
TI  - Transrectal ultrasonography for the detection and staging of carcinoma of the
      prostate.
AB  - Transrectal ultrasonography (TRUS) has become the most frequently used imaging
      modality for the prostate. The internal architecture of the prostate is readily
      detailed by TRUS, and the procedure allows an accurate measurement of prostate
      size. Carcinoma of the prostate has a characteristic hypoechoic pattern which is
      sometimes distinct from the normal echo pattern of the peripheral portion of the
      prostate. TRUS does not have sufficient sensitivity and specificity to support
      its use for routine screening for prostate cancer. In men with an abnormality of
      either digital rectal palpation of the prostate or serum prostate specific
      antigen, TRUS is useful for directing prostate biopsy. Transrectal core biopsies
      are obtained under ultrasound direction, and precise placement of the biopsy
      needles can be accomplished using TRUS.

PMID- 8884523
TI  - Role of transrectal ultrasound and prostate biopsy.
AB  - Transrectal ultrasound (TRUS) has revolutionized our ability to image the human
      prostate. In the present review, we have attempted to present salient
      observations with respect to this modality. We emphasize its use in combination
      with biopsy in men who are considered at risk for harboring carcinoma. The
      relevant English literature is reviewed. In addition, our experience with 2,231
      consecutive ultrasound-guided biopsies performed at the University of Washington
      and the Seattle VA Medical Center is analyzed. TRUS appears to have its primary
      use in directing the biopsy needle into suspicious areas and in performing the so
      called systematic sector approach to biopsy. The role of transrectal ultrasound
      in staging established malignancy or in monitoring men following therapy remains
      to be defined. In our experience, carcinoma was detected in 27.2% of the
      subjects. Carcinoma was found in 30.7% of patients with a hypoechoic sector. Of
      note, 18.4% of men had their only carcinoma found in isoechoic areas. Failure to
      biopsy isoechoic sectors would have resulted in missing almost 20% of men with
      carcinoma. The role of TRUS in men with initially negative biopsy is also
      discussed. In summary, ultrasound guided biopsy is a useful addition to our
      armamentarium, particularly with respect to performing biopsy. Future advances in
      this modality include image enhancement utilizing computer technology as well as
      the potential additive role of color flow ultrasound.

PMID- 8884524
TI  - Ultrasound evaluation of the male urethra for assessment of urethral stricture.
AB  - Radiographic retrograde urethrography has traditionally been the preferred
      technique used by urologists to image the anterior urethra. Since originally
      described by McAninch in 1988, ultrasonic imaging of the urethra has evolved into
      a powerful and clinically useful tool for the accurate delineation of urethral
      pathology. Although posterior urethral and peri-urethral fibrosis cannot be
      assessed reliably using this technique, sono-urethrography has proven to be more
      accurate than conventional radiographic urethrography in measuring stricture
      length throughout the anterior urethra. Herein we describe the evolution of sono
      urethrography, explain its many advantages over traditional imaging techniques,
      and show clinical examples of its importance in guiding the successful
      reconstruction of urethral strictures, particularly in the bulbar area.

PMID- 8884525
TI  - Ultrasound evaluation of the penis for assessment of impotence.
AB  - Image directed Doppler ultrasonography of the cavernous arteries provides
      functional, quantifiable assessment of penile arterial flow during a
      pharmacological erection. In this respect, this modality is superior to
      arteriography as a means of evaluating arteriogenic impotence. Peak flow
      velocity, arterial dilatation, and vessel pulsation are the most reliable
      ultrasonic indicators of arterial health. Aberrant arterial anatomy should be
      noted as this may contribute significantly to total penile blood flow. A thorough
      understanding of erectile physiology and anatomy is necessary to properly perform
      and interpret Doppler ultrasound results.

PMID- 8884526
TI  - ICAM-1 expression on keratinocytes in mechanically-injured skin of a patient with
      atopic dermatitis.
AB  - The expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes was
      studied in skin specimens of patch- or scratch-test using Dermatophagoides
      farinae (DF) antigen in atopic dermatitis (AD). Positive patch test reaction
      showed exocytosis of lymphocytes and focal expression of ICAM-1 on keratinocytes.
      Similar lymphocyte infiltration and keratinocyte expression of ICAM-1 were
      observed in tape-stripped skin which was subjected as the control. In addition,
      focal ICAM-1 expression on keratinocytes was also observed without exocytosis of
      lymphocytes. By scratch-test with DF antigen, ICAM-1 expression on keratinocytes
      was observed in eight out of eleven patients. One specimen showed ICAM-1
      expression in spite of the absence of exocytosis of lymphocytes. Two out of three
      specimens from negative scratch-test sites with control liquid (mixture of equal
      amount of saline and glycerine) showed ICAM-1 expression in a similar manner to
      that of the positive scratch tests. In normal control skin, patch-test sites
      showed focal and weak expression of ICAM-1. Normal appearing skin of AD also
      showed no ICAM-1 expression. Therefore, in patients with atopic dermatitis,
      keratinocytes may express ICAM-1 prior to infiltration of lymphocytes into the
      epidermis and this expression might be induced not only by cytokines produced by
      lymphocytes but also by mechanically injured (tape-stripped or scratched)
      epidermal cells.

PMID- 8884527
TI  - Application of non-radiolabeled in situ hybridization system for the detection of
      polyadenylated RNA to normal and psoriatic human skin.
AB  - The concentration and distribution of total mRNA is thought to reflect cellular
      activity. To clarify the distribution of total mRNA in normal and psoriatic human
      skin, in situ hybridization with a digoxigenin-labeled poly(dT) probe was carried
      out. In normal skin, polyadenylated RNA was distributed uniformly throughout the
      epidermis, including the basal, spinous, and granular layers. The nucleus and
      cytoplasm of skin appendages were stained more strongly than those of epidermal
      cells. The concentration of total mRNA in the epidermis of psoriatic skin was
      thought to be increased because of strong staining, especially in the basal
      layer, compared with that in normal epidermis, possibly reflecting
      hyperproliferation of keratinocytes. Results suggest that in situ hybridization
      with a poly(dT) probe is a useful strategy to study total mRNA distribution in
      human skin.

PMID- 8884528
TI  - Analysis of connective tissue macromolecular components in Ishibashi rat skin:
      role of collagen and elastin in cutaneous aging.
AB  - The Ishibashi (IS) rat, established from cross-breeding between Wistar and wild
      rats, has a unique skin appearance, with wrinklings and furrows indicative of
      skin aging appearing at the age of 12 weeks. To understand the underlying
      mechanism of the formation of wrinkles, macromolecular components of connective
      tissue, collagen and elastin, in the young (5-6-week-old) and the aged (23-30
      week-old) IS rat skins were biochemically analyzed. Hydroxyproline and
      isodesmosine contents in the aged IS rats were reduced 22% (P < 0.05) and 37% (P
      < 0.05) compared to the young rats, whereas no significant differences in the
      contents of both macromolecules in control Sprague-Dawley (SD) rats were seen.
      The relative content of type III collagen was unaltered between the young and
      aged skins of both IS and SD rats. A relative decrease in the intact elastin
      molecule (65 kDa) and a relative increase in the elastin fragments with lower
      molecular weights were observed in the aged IS rat skin by immunoblotting method.
      These results indicate that the reduction in collagen and elastin contents and
      increased degradation of elastin molecules in the aged IS rat skin could be
      related to the formation of wrinkles. Thus, the IS rat may provide a useful model
      for the study of skin aging.

PMID- 8884529
TI  - Comparative epitope mapping of sera from United States (US) and Japanese patients
      with bullous pemphigoid (BP) to fusion proteins encoded by BPAG1.
AB  - Sera from patients with bullous pemphigoid (BP) from the United States (US),
      Japan, and Britain demonstrate similar reactivity to the major target antigens
      BPAG1 and BPAG2. The purpose of the present study was to determine if the epitope
      specificity of circulating autoantibodies in patients with BP from the US and
      Japan is similar as mapped by binding to fusion proteins encoded by BPAG1. Sera
      from patients and controls with BP from the US and Japan were assayed for
      reactivity to intact BPAG1 and BPAG2 by immunoblot, and to fusion proteins
      encoded by BPAG1 by immunoblot and enzyme-linked immunosorbant assay (ELISA).
      Significant reactivity to fusion proteins encoded by the carboxyl region (FP 16
      8) and coiled-coil region (FP3) was seen in sera from the US and Japanese
      patients, but not from normal controls from the US or Japan. Sera from US and
      Japanese patients differed in their response to FP7; namely, the reactivity of
      sera from US patients but not from Japanese patients to FP7 was significantly
      different from the reactivity of their respective control sera. The reasons for
      this difference in reactivity are unknown but may reflect genetic or
      environmental factors relevant in the generation of an autoantibody response to
      these target antigens.

PMID- 8884530
TI  - FK506 and cyclosporin A inhibit growth factor-stimulated human keratinocyte
      proliferation by blocking cells in the G0/G1 phases of the cell cycle.
AB  - FK506, a new immunosuppressive agent, is effective in treating patients with
      psoriasis. A major feature of psoriasis vulgaris is the hyperproliferation of
      keratinocytes together with inflammation. To determine the effect of FK506 or
      cyclosporin A (CsA) on the keratinocyte cell cycle, flow cytometry and the growth
      factor free normal human keratinocyte-arrested system were used to assess
      keratinocyte proliferation. FK506 and CsA inhibit keratinocyte proliferation
      induced by EGF, TGF-alpha or IL-6. The antiproliferative effects of FK506 and CsA
      directly correlated with blockade of the keratinocyte cell cycle at the G0/G1
      phases. These findings might indicate that the effects of FK506 and CsA on
      proliferation of cultured normal human keratinocytes are probably related to
      direct effects on growth regulation of keratinocytes via EGF, TGF-alpha or IL-6
      stimulation.

PMID- 8884531
TI  - The mitogen-activated protein kinases system (MAP kinase cascade): its role in
      skin signal transduction. A review.
AB  - Mitogen-activated protein (MAP) kinases are proline-directed kinases which are
      downstream components of a pathway involving p21ras and the serine/threonine
      kinase Raf-1. They represent an important link between the signal transduction
      processes at the level of the plasma membrane and the final nuclear events. Not
      only various growth factors and cytokines, but also other signals such as UV
      light or extracellular matrix components are able to activate MAP kinases. We
      believe that the MAP kinase cascade may play a significant role in regulating
      cell proliferation and differentiation in human epidermis. In this review we
      summarize the rapidly increasing knowledge in this field of signal transduction
      and discuss some very recent results on MAP kinases and their role in skin
      biology.

PMID- 8884532
TI  - Regulation of Langerhans cell function via blood borne factor(s).
AB  - Langerhans cells (LC) are epidermal dendritic cells that are functionally labile.
      Freshly obtained LC (fLC) readily activate allogeneic T cells, but they are
      incapable of activating autologous T cells; and even when pulsed with antigen,
      they fail to activate naive, antigen-specific T cells. When fLC are cultured for
      2-3 days in the presence of keratinocytes, LC swiftly up-regulate surface
      expression of class I and II MHC molecules, and express de novo the co
      stimulatory molecules B7 and ICAM-1. In addition to displaying enhanced ability
      to activate allogeneic T cells, cultured LC acquire the novel functional property
      of activating autologous T cells. It is believed that keratinocyte-derived GM-CSF
      is the primary driving force responsible for the conversion of fresh to cultured
      LC in vitro. However, in vivo administration of GM-CSF, either intracutaneously
      or systematically, fails to induce LC to undergo functional transformation in
      situ. Moreover, despite a high level of GM-CSF in the circulation, fLC from mice
      bearing GM-CSF-producing tumors display no ability to activate syngeneic T cells.
      These observations suggest that a homeostatic factor that antagonizes the effect
      of GM-CSF may be present in vivo. To test this possibility, we have examined the
      functional properties of LC prepared from mouse skin that had been explanted in
      vitro for 3 days. We found that the functional and phenotypic features of these
      cells closely resembled those of LC cultured in single cell suspension: the cells
      strongly expressed B7-1 and B7-2, and displayed enhanced expression of class II
      MHC molecules; they readily activated naive autologous T cells. Strikingly, when
      explants or suspensions of fresh epidermal cells were cultured in the presence of
      10% mouse serum they failed to acquire syngeneic T cell activating properties;
      and surface up-regulation of Ia and de novo expression of B7 was inhibited.
      However, the cultured cells still expressed surface Ia and readily activated
      allogeneic naive T cells. If mouse serum was added only during the last 24 h of
      culture, the LC displayed full functional transformation. Human, rabbit and
      bovine serum showed no inhibitory effect on mouse LC. Our data suggest that mouse
      serum contains a factor (or factors) that inhibits, in a species-specific manner,
      epidermal LC from undergoing functional transformation in vitro, and this factor
      may maintain epidermal LC in the 'fresh' functional program in vivo.

PMID- 8884535
TI  - TGF beta 1 immunostaining patterns and locations in adenoma which later recurred.
AB  - To investigate whether the immunohistochemical pattern of TGF beta 1 may be a
      marker of relapse for adenomatous pathology, 18 follicular adenomas, surgically
      removed by hemithyroidectomy between 1977 and 1982, were studied. The adenomas
      were divided into two groups according to the presence (group 1, N = 9) or
      absence (group 2, N = 9) of nodules recurring in the residual thyroid tissue. The
      presence and location of TGF beta 1 were evaluated a posteriori by
      immunohistochemistry in the removed adenoma. Fifty randomly selected subcapsular
      follicles were studied in each adenoma in order to evaluate the percentage of
      positive follicles and TGF beta 1 intra-thyrocyte location. In adenoma of group
      1, the percentage of positive follicles for TGF beta 1 was lower (80%) than in
      adenoma of group 2 (84%); this was, however, not statistically significant. The
      location of TGF beta 1 was mainly at the cell base of the epithelial cells in the
      microfollicles of group 1, but was dominant at the cell apex in group 2 (p <
      0.01). In conclusion, adenoma recurrence is independent of TGF beta 1 production;
      it may be due to an abnormal TGF beta 1 regulation in response to
      hyperplasiogenic stimuli.

PMID- 8884533
TI  - Thyrotropin receptor antibodies in parotid saliva.
AB  - Parotid saliva was collected with a Carlson-Crittenden device, under citric acid
      stimulation, in 18 patients with autoimmune thyroid disease. Thyrotropin Receptor
      Antibodies (TRAb) were measured with a radioreceptor assay in parotid saliva and
      in serum in the same patients, and a statistical analysis of the data was
      performed. TRAb levels in parotid saliva were higher than in serum in the 3
      pathologies studied (Graves' disease, Hashitoxicosis and Hashimoto's
      thyroiditis). There was good correlation between salivary and serum levels.

PMID- 8884534
TI  - Lipopolysaccharides selectively inhibit mouse placental lactogen-II secretion
      through stimulation of interleukin-1 alpha (IL-1 alpha) and IL-6 production.
AB  - To determine whether lipopolysaccharides (LPS) regulate mouse placental lactogen
      I (mPL-I), mPL-II, and mouse GHRF (mGHRF) secretion, mouse placental tissue from
      days 7, 9, and 12 of pregnancy was dispersed with collagenase and the purified
      trophoblast cells were cultured in a serum-free medium with or without LPS for 5
      days. LPS significantly inhibited mPL-II secretion by cells from days 9 and 12 of
      pregnancy. However, LPS did not affect mPL-II secretion by cells from day 7 of
      pregnancy, mPL-I secretion by cells from days 7 and 9 of pregnancy, or mGHRF
      secretion by cells from day 12 of pregnancy. The inhibitory effect of LPS on mPL
      II secretion by cells from day 12 of pregnancy was dose-dependent. Steady-state
      levels of mPL-II mRNA were significantly reduced by incubation of placental cells
      from day 12 of pregnancy with LPS. The inhibitory effect of LPS on mPL-II
      secretion was abolished by the addition of antibodies to IL-1 alpha and IL-6.
      These findings suggest that LPS selectively inhibit mPL-II secretion, at least
      partly through increases in IL-1 and IL-6 production, after midpregnancy.

PMID- 8884536
TI  - Nasal spray vs oral administration of bromocriptine: pharmacology and effect on
      serum prolactin in puerperal women.
AB  - The oral administration of bromocriptine induces a variety of side-effects in
      about 50-70% of patients, the most common being nausea and vomiting, probably
      related to the local gastrointestinal effect of the drug. Nasal administration
      makes it possible to avoid intestinal and liver metabolism. This study compared
      the serum concentrations of bromocriptine and prolactin (PRL) in twenty puerperal
      women who had asked to discontinue breast feeding and were randomized to receive
      a single oral (2.5 mg) or nasal spray dose (0.8 mg) of bromocriptine. Serum
      bromocriptine and PRL concentrations were measured at various times before and
      after drug administration. At 15 min, the circulating concentrations of
      bromocriptine were about eight times higher after nasal than after oral
      administration; peak serum concentration (CMax) was reached respectively 45 min
      and 60 min after administration, and was about three times higher after nasal
      administration (314 +/- 102 pg/ml vs 112.30 +/- 34.47 pg/ml). The reduction in
      serum PRL concentrations was also more rapid in the nasally-treated group
      reaching the normal assay range of < 20 micrograms/l within two as against five
      hours post-administration. Four orally-treated patients complained of nausea; in
      the nasally-treated group, six patients reported only a mild endonasal burning
      that disappeared within a few minutes of administration. Our results suggest that
      the nasal administration of bromocriptine may lead to a reduction in the required
      overall dose and fewer gastrointestinal side-effects, and may therefore improve
      therapy compliance.

PMID- 8884537
TI  - Effect of glycemic control on growth hormone and IGFBP-1 secretion in patients
      with type I diabetes mellitus.
AB  - Growth hormone (GH) secretion disorders have been reported in poorly controlled
      type I diabetes mellitus patients. Our work was aimed to evaluate GH secretion in
      9 type I young diabetes mellitus patients as well as the low molecular weight IGF
      binding protein secretion (IGFBP-1) in 5 of them. The patients did not show any
      signs of malnutrition or neurovascular complications, neither were they on any
      medication except for insulin. The study protocol included blood samples
      collection during a 24-h period for measurement of glucose, glycated hemoglobin,
      GH IGF-I and IGFBP-1 levels under two situations: on poor glycemic control and
      after 2-3 months on better control through systematic diet, low in carbohydrates
      and increase in insulin dosage. GH secretion data were analyzed by Cluster
      algorithm for pulsatility parameters; for rhythm assessment Cosinor method was
      used. The first study (poor control) reported significant increase of GH maximal
      and incremental amplitude and duration pulse values, when compared to the second
      study (better control). Mean 24-h secretion values as well mean GH for interpulse
      intervals (valleys) decreased, although not statistically significant. The
      fraction of pulsatile GH/24 h GH did not change significantly with better
      glycemic control. No changes in pulse frequency were observed. Mean IGF-I
      concentrations were significantly higher when patients were on better glycemic
      control. An ultradian variation for GH secretion was noticed in the first study
      (poor control) and a circadian variation in the second one (better control).
      IGFBP-1 analysis showed significant decrease of the mean 24-h values under better
      glycemic control. Linear regression analysis demonstrated a correlation between
      IGFBP-1 levels and fasting glucose levels. A circadian variation was present in
      IGFBP-1 secretion, irrespective of glycemic control. Therefore, we concluded that
      for type I diabetic patients: 1. GH secretion is increased on poor control,
      through maximal, incremental amplitude and pulse duration values; 2. IGFBP-1
      values were significantly reduced and IGF-1 levels significantly higher after
      better glycemic control; 4. GH ultradian secretion is reported on poor control,
      and circadian on the better one, 5. IGFBP-1 circadian secretion occurred
      irrespective of glycemic control.

PMID- 8884538
TI  - Total body zinc depletion and its relationship to the development of
      hyperprolactinemia in chronic renal insufficiency.
AB  - Modulation of free plasma zinc levels has been implicated in the increase in
      plasma prolactin levels seen in patients with chronic renal insufficiency (CRI).
      The relative importance of this mechanism in comparison to others, however, has
      not been elucidated. Zinc equilibrium between plasma and red blood cells is
      partly dependent upon red blood cell carbonic anhydrase (CA). In the present
      paper, we have investigated the interrelationships among total plasma zinc,
      leukocyte zinc, prolactin, and erythrocyte CA in patients with CRI. Uremic
      patients were shown to have significantly increased levels of plasma prolactin
      and erythrocyte CA activity when compared to normal controls. Moreover, red blood
      cell CA total concentration and isoenzyme-I and-II levels, as well as plasma zinc
      were found to be significantly decreased in uremic patients in comparison to
      normal controls. In patients with CRI, a negative correlation was demonstrated
      between erythrocyte CA catalytic activity and plasma zinc, as well as between
      plasma zinc and plasma prolactin levels. Moreover, leukocyte zinc content, which
      is a reliable indicator of total body zinc stores, was found to be significantly
      decreased in uremic patients when compared to normal controls. A strong negative
      correlation between leukocyte zinc content and plasma prolactin levels was
      documented in CRI patients. Our results suggest that alterations in erythrocyte
      CA levels, enzymatic activity or isoenzyme profile are most probably
      mechanistically and etiologically unrelated to the high plasma prolactin levels
      in CRI patients. Contrariwise, depletion of total body zinc stores, rather than
      redistribution of this trace metal among extracellular compartments, may
      represent one of the major contributing mechanisms leading to uremic
      hyperprolactinemia.

PMID- 8884539
TI  - Central and peripheral neural responses in males with idiopathic hypogonadotropic
      hypogonadism.
AB  - It has previously been shown that abnormal neurophysiologic responses are
      associated with Kallmann's syndrome. However, little is known about
      neurophysiologic responses in idiopathic hypogonadotropic hypogonadism (IHH).
      Fifty-six untreated male patients with IHH (mean age: 20 +/- 0.7 years) were
      compared with a control group of 20 age-matched male subjects to determine
      whether IHH can lead to alterations in somatosensory evoked potentials (SSEPs)
      and brainstem auditory evoked potentials (BAEPs). We have also investigated the
      effect of gonadotropin replacement (hCG/hMG) therapy on these tests in 20
      randomly selected patients. Significant cervical 7 (N13), Erb (N9) and thoracic
      12 (N22) latency prolongation was observed in median and tibial nerve SSEPs in
      patients with IHH as compared with a matched control group. Other components of
      SSEPs and interpeak latencies of BAEPs yielded no significant difference between
      untreated patients and control group. Abnormal components of SSEPs did not
      correlate with basal hormone levels and did not improve with gonadotropin
      therapy. We conclude that IHH results abnormalities in peripheral but not central
      nervous system components of SSEPs and that short term gonadotropin treatment
      cannot correct these abnormalities.

PMID- 8884540
TI  - Intracranial volume receptors: possible role on ADH homeostatic control.
AB  - Volume receptors are situated in many organs and are capable of modulating ADH
      secretion. We have evaluated the variation of plasma ADH concentration after an
      experimentally induced increase of cerebrospinal fluid (CSF) pressure (PCSF). The
      experiment was performed in controlled environmental conditions to avoid pain or
      stress-related ADH release. In 15 rats (10 experimental, 5 control) a cannula was
      positioned in the left cerebral ventricle: in the experimental group artificial
      CSF was infused at a rate of 0.6 (microliter/min for 6h: this manoeuvre, in a
      separate set of animals obtained an increase from 13.03 +/- 0.8 to 25.4 +/- 2.5
      cmH2O of PCSF. The same conditions were reproduced in the control group without
      infusion into lateral ventricle. At the end of the experiment, plasma ADH had
      fallen significantly in the experimental group from 18.9 +/- 4.8 to 11.9 +/- 2.3
      pg/ml (p < 0.05), while it was not changed in the control group (from 25.5 +/-
      13.7 to 23.7 +/- 16.2 pg/ml). Heart rate, arterial pressure, plasma Na+ and
      osmolality, did not change significantly. Plasma K+ fell significantly in both
      groups: from 5.5 +/- 0.6 to 4.3 +/- 0.3 (p < 0.05) and from 5.4 +/- 0.7 to 4.3 +/
      0.15 mEq/l (p < 0.05) in the experimental and control group respectively. Plasma
      creatinine was normal, checked only at the end of the experiment. Our results
      demonstrate that a relationship exists between PCSF variations and plasma ADH
      concentration. We believe this relationship is due to the pressure receptors in
      the cerebral ventricles or in structures connected to it, such as the inner ear,
      and we hypothesize the existence of a control system of body fluids, more
      diffused than though to be, up till now.

PMID- 8884541
TI  - Cortisol in human tissues at different stages of life.
AB  - Aim of the work was to measure the cortisol level in human tissues at different
      stages of life, by means of radioimmunoassay and by chromatography. Viable
      samples of 13 different tissues were obtained during surgical intervention from
      30 to 70 years old patients of either sex. Mean tissue cortisol concentration was
      78 +/- 35 ng/g, ranging from 20 +/- 10 ng/g in the thyroid to 124 +/- 76 ng/g in
      the kidney. Similar values were measured in the corresponding tissues from not
      decayed corpses, so that paired values could be mediated. However the pancreas,
      and corrupted autopsy tissues, gave nil or exceedingly high cortisol
      concentration values; in some cases, opposite extreme values were measured in
      different organs of the same body. Cortisol concentration was also measured in 11
      sound different tissues of spontaneously aborted or stillbirth fetuses, between
      16 and 36 weeks of gestation. Mean value was 63 +/- 27 ng/g, ranging from 30 +/-
      25 ng/g in the liver to 104 +/- 52 ng/g in the lungs. Also in fetuses nil or
      exceedingly high cortisol values occurred in altered tissues. One hundred and
      fourteen samples of limbs and carcasses of 7 to 12 gestational weeks embryos,
      obtained from voluntary abortions, were also examined: 20% gave nil result, in
      the remaining mean cortisol concentration was 32 ng/g. In 33 samples of embryos'
      mixed viscera, RIA and chromatography gave unreliable exceedingly high values.
      The nil and the exceedingly high values measured in the altered autoptic tissue
      specimens were inconsistent with the cortisol blood level measured in the
      patients, as were those measured in embryonic tissues with the acknowledged blood
      and adrenals cortisol levels at that stage of life. Thus cortisol may be measured
      by RIA and by chromatography in sound tissues, while the values obtained in the
      pancreas, in corrupted tissues, and in embryonal viscera do not represent the
      hormonal milieu, but are likely artifacts due to impeachment of the diagnostic
      system.

PMID- 8884542
TI  - Treatment with long acting repeatable bromocriptine (Parlodel-LAR*) in patients
      with macroprolactinomas: long-term study in 29 patients.
AB  - The aim of the study was to evaluate the short term and long-term effects of long
      acting repeatable bromocriptine (= Parlodel-LAR*) in patients with
      macroprolactinomas. Twenty-nine patients (15 men and 14 women) aged 42 +/- 2.7 (M
      +/- SEM) years were injected with Parlodel-LAR* every 4 weeks during 3.3 +/- 0.3
      years. The starting dose was 50 mg/injection, then it was increased to 100 mg in
      11 patients and 150 mg in 9 patients. PRL levels decreased in all but one patient
      4 weeks after the first injection (270 +/- 59 vs 934 +/- 210 ng/ml, p < 0.001),
      then became less than 20 ng/ml in 20/29 (69%) patients and finally became
      undetectable or low in 13/29 (45%) patients. Visual field defects were present in
      12/29 patients before treatment. In 11/12 patients, treatment with Parlodel-LAR*
      resulted in an improvement and complete correction of visual field defects was
      observed in 8/12 patients. Adenoma size (2.5 +/- 0.2 cm before treatment) was
      reduced by at least 20% in 24/29 (83%) patients. Disappearance of adenoma was
      observed on CT scan in 8/29 (28%) patients after 28.7 +/- 5.3 months of
      treatment. Minor side effects occurred in 20 patients after the first injection
      then disappeared in 18 patients within the following 6 months of treatment. One
      patient had rhinorrhea after 3 months of treatment. Treatment with Parlodel-LAR*
      results in beneficial short-term effects (with rapid correction of recent onset
      visual field defects) and long-term effects (which can include complete
      disappearance of adenoma on CT scan evaluation) in patients with
      macroprolactinomas.

PMID- 8884543
TI  - Relationship between serum 3,5,3'-triiodothyronine and serum interleukin-8,
      interleukin-10 or interferon gamma in patients with nonthyroidal illness.
AB  - In order to further delineate the role of cytokines in the pathogenesis of the
      low T3 syndrome, we studied the association between serum T3 and serum interferon
      gamma (IFN gamma), interleukin-8 (IL-8) and interleukin-10 (IL-10) in 99
      consecutive patients hospitalised because of a wide variety of nonthyroidal
      diseases; none used drugs affecting thyroid hormone metabolism. Patients were
      divided in group A (normal serum T3 and T4), group B (subnormal serum T3 and
      normal T4) and group C (subnormal T3 and T4). Serum IFN gamma, IL-8 and IL-10
      were not different between group A, B and C (with the exception of a small
      increase of IFN gamma in group B). Serum T3 was slightly related to serum IL-8 (r
      = 0.25, p < 0.05), but not to IFN gamma and IL-10. Stepwise multiple regression
      indicated that these serum cytokines were not independent determinants of the
      variability in serum T3. The results do not support any role of circulating IFN
      gamma, IL-8 or IL-10 in the pathogenesis of the low T3 syndrome during illness.

PMID- 8884544
TI  - Clinical features and hormonal characteristics in a case of ovarian
      arrhenoblastoma.
AB  - We report a case of a 34-year-old woman affected with ovarian arrhenoblastoma
      characterized by very high testosterone (T) levels (34.0-60.0 ng/ml; n.v.0.2-0.9)
      and suppressed gonadotropin levels. The physical examination revealed: severe
      hirsutism, acne, amenorrhea and other virilization signs. Basal hormonal
      evaluation also showed a markedly elevated 17-hydroxyprogesterone (17-OHP) and a
      mild delta 4 Androstenedione (A) and dehydroepiandrosterone sulfate (DHEAs)
      increase. ACTH test induced only slight changes in androgen secretion. By
      contrast, dexamethasone test greatly decreased A and DHEAs whereas T levels were
      only partially suppressed. Moreover, hCG test was clearly stimulatory for T and
      A. Suppressed gonadotropin levels did not respond to LHRH stimulation. The
      removal of the neoplasia was followed by normalization of T levels and increase
      of serum gonadotropins with subsequent restoration of a normal responsiveness to
      LHRH and resumption of an ovulatory menstrual cycle. This observation suggests
      that the high T levels played a primary role in the pathogenesis of the
      gonadotropin suppression and anovulation. Recovery of acne was complete whereas
      hirsutism score was reduced but still elevated after one year. This may be due to
      postoperative A and DHEAs levels slightly above the normal range, indicating the
      presence of adrenal hyperandrogenism.

PMID- 8884545
TI  - An unusual case of adrenal failure due to isolated metastases of breast cancer.
AB  - We describe a patient affected by adrenal insufficiency due to metastases of
      breast cancer. Adrenal involvement became clinically evident 20 years after
      radical mastectomy and it was the only secondary localization of the tumor. There
      is still no evidence of other metastases after a two year follow-up. This case
      suggests that adrenal function evaluation should be included in periodical follow
      ups of patients who underwent radical mastectomy for breast cancer.

PMID- 8884546
TI  - The 1996 report of a World Health Organization expert committee on hypertension
      control.

PMID- 8884547
TI  - Is blood pressure inversely related to birth weight? The strength of evidence
      from a systematic review of the literature.
AB  - OBJECTIVE: To assess the strength of evidence for an inverse relationship between
      blood pressure and birth weight. DESIGN: A systematic review of the published
      literature. SETTING: Published studies describing the relationship between blood
      pressure and birth weight since 1956. SUBJECTS: More than 66,000 subjects aged 0
      71 years. RESULTS: Thirty-four studies described the relationship of blood
      pressure with birth weight. The majority of the studies of children and adults
      showed that blood pressure fell with increasing birth weight. Studies of
      adolescents were inconsistent. In neonates there was a positive relationship
      between blood pressure and birth weight. The pattern with age was supported by
      the limited number of studies with repeated measures and was dependent neither on
      the method of analysis nor on work from a single academic group or country.
      CONCLUSIONS: Blood pressure is inversely related to birth weight in children and
      in adults. The positive results in neonates and the inconsistency in adolescence
      may be related to the unusual growth dynamics during these phases of growth.
      Further studies should concentrate on the mechanisms which underlie the
      relationship.

PMID- 8884548
TI  - Associations of orthostatic blood pressure fall in older patients with isolated
      systolic hypertension. Syst-Eur Investigators.
AB  - OBJECTIVES: To investigate the associations of the orthostatic blood pressure
      changes in older patients with isolated systolic hypertension. METHODS: A total
      of 2716 patients, 917 men and 1799 women, aged > or = 60 years, were examined at
      three separate outpatient visits whilst receiving placebo during the single-blind
      run-in phase of the Syst-Eur trial. The orthostatic blood pressure changes were
      calculated by subtracting the average of two blood pressure readings with the
      patient in the supine position from the mean of two readings obtained after the
      patient had stood for 2 min. An orthostatic blood pressure drop by at least 20
      mmHg systolic or 10 mmHg diastolic was considered exaggerated. RESULTS: For the
      three run-in visits combined, the supine blood pressure was 175 +/- 13 mmHg
      systolic and 86 +/- 6 mmHg diastolic (means +/- SD). With the patients standing
      the systolic blood pressure was 5 +/- 12 mmHg lower, whereas the diastolic blood
      pressure was 2 +/- 7 mmHg higher. An exaggerated fall in systolic blood pressure
      was observed on at least 1 visit in 21.0% of the patients and on all three visits
      in 2.5%. The corresponding values for diastolic blood pressure were 9.7 and 0.4%.
      The orthostatic fall in systolic blood pressure increased with previous
      antihypertensive treatment, age and smoking, but decreased with a higher sitting
      pulse rate and usual alcohol consumption versus none. The rise in diastolic blood
      pressure upon standing was higher in women than in men, was curvilinearly
      associated with age and increased with the sitting diastolic blood pressure. By
      multiple logistic regression analysis, the odds of having a persistent or
      occasional exaggerated orthostatic fall in systolic blood pressure were 22%
      higher in women than in men. The odds increased with previous antihypertensive
      treatment (by 42%), age (by 1.4%/year), electrocardiographic left ventricular
      mass (by 15%/mV) and sitting systolic blood pressure (by 0.9%/mmHg), but
      decreased with sitting pulse rate (by 1.9%/beat per min). An exaggerated
      orthostatic fall in diastolic blood pressure was 30% more likely in men; the
      likelihood increased with age (by 6.4%/year) and decreased with sitting diastolic
      blood pressure (by 6.6%/mmHg). CONCLUSION: An exaggerated orthostatic blood
      pressure fall in older patients with isolated systolic hypertension is associated
      mainly with gender, age and blood pressure level. Previous antihypertensive
      treatment, a lower pulse rate and a lower electrocardiographic left ventricular
      mass were also associated with an exaggerated orthostatic fall in systolic blood
      pressure.

PMID- 8884549
TI  - Cerebral metabolism and its relationship with sympathetic nervous activity in
      essential hypertension: evaluation of the Dickinson hypothesis.
AB  - OBJECTIVE: To examine Dickinson's hypothesis in mild essential hypertension, in
      which neurogenic mechanisms are believed to be particularly relevant, by
      combining measures of cerebral oxygen consumption with the concurrent assessment
      of sympathetic nervous activity. DESIGN AND METHODS: Twenty-five untreated
      essential hypertensive subjects and 28 healthy age-matched volunteers underwent
      direct blood sampling using percutaneously inserted catheters advanced into the
      internal jugular vein, with cerebral blood flow scans to differentiate between
      cortical and subcortical venous drainage of the brain. Venoarterial blood gas
      measurements and internal jugular vein blood flows were used to calculate
      cerebral respiratory quotients and cerebral oxygen utilization. The total body
      rate of noradrenaline spillover into plasma was measured to assess relationships
      between cerebral oxidative metabolism and sympathetic nervous activity. RESULTS:
      Compared with controls, the hypertensive subjects exhibited reductions in
      internal jugular vein blood flow (482 +/- 29 versus 410 +/- 15 ml/min), cerebral
      oxygen consumption (27 +/- 2 versus 23 +/- 1 ml/min) and cerebral oxygen supply
      (93 +/- 6 versus 78 +/- 3 ml/min). The cerebral respiratory quotients were
      identical (1.00 +/- 0.04 in normotensives and 0.98 +/- 0.03 in hypertensives).
      Technetium blood flow scans revealed that the reductions in internal jugular
      blood flow and cerebral oxygen consumption in the hypertensive patients were
      confined to cortical brain regions. Cortical blood flow was quantitatively linked
      to the matching respiratory quotient and oxygen consumption, neither of which
      bore any relation to the level of sympathetic nervous activity. The spillover of
      noradrenaline into the plasma for the body as a whole did not differ between the
      two groups. CONCLUSIONS: In accord with Dickinson's hypothesis, we have
      established a reduction in internal jugular vein blood flow and cerebral oxygen
      utilization in hypertension. These reductions were confined to cortical brain
      regions. However, cerebral respiratory quotients in our hypertensive study group
      were no different from those in our controls, suggesting that glucose remained as
      the major cerebral metabolic substrate in hypertension. We were not able to
      establish a link between cerebral metabolism and blood pressure or sympathetic
      nervous activity in mildly hypertensive patients.

PMID- 8884550
TI  - Hepatic angiotensin II nuclear receptors and transcription of growth-related
      factors.
AB  - OBJECTIVES: To investigate the influence of angiotensin II (All) receptors in
      isolated hepatic nuclei on other genes regulated by All and to determine whether
      the function of these intracellular receptors is influenced by alterations in the
      endocrine renin system. METHODS: Nuclei were isolated from hepatic tissue of
      normal and bilaterally nephrectomized or adrenalectomized Wistar rats. Following
      nuclear run-off, in the presence of varying All concentrations, specific
      messenger RNAs (mRNA) were determined by slot blot hybridization. Tissue levels
      of renin system components were measured by radioimmunoassay and nuclear
      receptors characterized by displacement of radiolabeled All with specific All
      receptor antagonists. RESULTS: All binding in the presence of DUP 753 and PD
      123177 confirmed that nuclear All receptors can be classified as AT1 receptors
      and that as much as 10% of the specific binding is attributable to nuclear
      chromatin. All stimulated not only the production of mRNA for renin system
      components such as renin and angiotensinogen, but also that of mRNA for growth
      related factors such as platelet-derived growth factor and the oncogene c-myc.
      Maximal stimulation occurred at 10(-9) mol/l All; higher concentrations reduced
      this response. After stimulation or suppression of the plasma renin system by
      adrenalectomy or bilateral nephrectomy, nuclei isolated from rat hepatic tissue
      contained elevated endogenous levels of growth-related and renin system mRNA
      including AT1 and AT2 All receptors. However, despite the level of receptor mRNA
      having been elevated, the total All receptor density of isolated nuclei
      decreased. In addition, after both maneuvers, isolated nuclei were refractory to
      All-induced gene transcription. CONCLUSION: The existence of mechanisms producing
      intracellular All and regulating its level, which in turn exert local regulatory
      responses via nuclear All receptors, lends significance to the presence of a
      functional intracrine renin system that could act in concert with or
      independently of the endocrine renin system.

PMID- 8884551
TI  - Erythrocyte Na(+)-Li+ countertransport in essential hypertension: correlation
      with membrane lipids levels.
AB  - OBJECTIVE: To examine whether Na(+)-Li+ countertransport (SLC) activity is linked
      to erythrocyte membrane lipid content. DESIGN: An observational case-control
      study. The maximal efflux rate of SLC, plasma cholesterol, triglycerides,
      phospholipids, low- and high-density lipoprotein cholesterol levels and the
      erythrocyte membrane cholesterol, phospholipids and fatty acids contents were
      determined both in fasting normolipaemic normotensive subjects and in
      hypertensive patients. METHODS: The Li(+)-stimulated Na+ efflux was measured in
      Li(+)-preloaded erythrocytes. Membrane cholesterol and phospholipids levels were
      determined by the latroscan technique. Membrane fatty acids were identificated by
      gas chromatography. Several derived indices were also obtained. RESULTS:
      Erythrocyte membranes of hypertensive patients showed an increase in cholesterol:
      phospholipid ratio and a decrease in the total amount of polyunsaturated fatty
      acids, mainly at the expense of arachidonic acid and docosatetraenoic acid. SLC
      activity was higher in hypertensive patients and correlated positively with the
      plasma triglycerides level and negatively with the ratio of C20:4 to C20:3.
      CONCLUSION: Our data from untreated normolipaemic hypertensive patients show that
      a higher SLC activity was accompanied by parameters that indicate a lower
      membrane fluidity.

PMID- 8884552
TI  - Acute hypertension after nitric oxide synthase inhibition is mediated primarily
      by increased endothelin vasoconstriction.
AB  - OBJECTIVE: To determine the quantitative roles played by the different
      vasoconstrictor systems in the acute pressor response in conscious rats before
      and after inhibition of nitric oxide synthase with Nw-nitro-L-arginine methyl
      ester (L-NAME). METHODS: In conscious male Sprague-Dawley rats, previously
      instrumented with aortic and venous catheters, the contributions of the different
      systems were assessed by maximal cumulative pharmacological blockade of alpha 1
      adrenoceptors (1 mg/kg prazosin intraperitoneally), AT1 receptors (30 mg/kg
      losartan intraperitoneally) and V1/V2 receptors (10 mg/kg [beta-mercapto-beta,
      beta-cyclopenta-methylenepropionyl1, O-Et-Tyr2-Val4-Arg8]-vasopressin per min
      intravenously). In addition, the contribution of endothelin-1-induced
      vasoconstriction in response to 100 mg/kg L-NAME intraperitoneally to the
      hypertension was assessed by administering 5-100 mg/kg ETA/ETB receptor
      antagonist PD 145 065 intravenously under three different conditions: as the last
      step of a series of antagonists in the cumulative pharmacological blockade after
      having induced the L-NAME pressor response; alone before L-NAME treatment; and
      alone after the full development of the L-NAME pressor response. A separate group
      of rats was treated acutely with 30 mg/kg losartan intraperitoneally or
      pretreated for 3 days with 30 mg/kg angiotensin I converting enzyme inhibitor
      enalapril via drinking water alone or in combination with 1% salt was used to
      assess the role of the renin-angiotensin system in the L-NAME-induced
      hypertension. RESULTS: Short-term administration of the combined ETA/ETB receptor
      antagonist PD 145065 did not change the arterial pressure under control
      conditions. Inhibition of the renin-angiotensin system, alpha 1-adrenoceptors or
      vasopressin receptors alone or in combination did not alter the magnitude of the
      L-NAME pressor response. In contrast, our results show that both treatments
      before and during acute nitric oxide synthase blockade hypertension using the
      ETA/ETB receptor antagonist PD 145065 abolished almost completely (approximately
      85%) the pressor response. CONCLUSIONS: These studies indicate that the
      predominant mechanism of hypertension, at least in the acute phase, after acute
      nitric oxide synthase blockade with L-NAME is associated with a marked increase
      in ETA/ETB receptor activation rather than with increases in alpha 1, AT1 and
      V1/V2 receptor activation. It remains to be determined whether endothelin
      participates also in the chronic phase of nitric oxide-deficient hypertension.

PMID- 8884553
TI  - Differential effects of vasopressin and endothelin-1 on vascular contractile and
      calcium responses in pressurized small arteries from spontaneously hypertensive
      rats.
AB  - OBJECTIVE: To investigate the effects of vasopressin and endothelin-1 on the
      intracellular free calcium concentration ([Ca2+]i) and on contractile responses
      in endothelium-denuded resistance vessels of prehypertensive (5-week-old) and
      adult hypertensive (17-week-old) spontaneously hypertensive rats (SHR) and age
      matched Wistar-Kyoto (WKY) rats. METHODS: Segments (2 mm long) of third-order
      branches of small mesenteric arteries were mounted in a perfusion myograph and
      maintained at 60 mmHg pressure. Endothelium was removed by intraluminal passage
      of air. The vessel [Ca2+]i was measured by fura-2 fluorescence and contraction
      was determined using a video imaging system to record lumen diameter. RESULTS:
      Lumen diameter was significantly smaller in 5-and 17-week-old SHR than it was in
      age-matched WKY rats (5 week-old SHR versus WKY rats: 178 +/- 4.0 versus 195 +/-
      4.3 microns; 17-week-old SHR versus WKY rats: 168 +/- 7.0 versus 230 +/- 3.1
      microns). The basal [Ca2+]i was significantly higher in 5- and 17-week-old SHR
      than it was in age-matched WKY rats. Infusions of vasopressin and endothelin-1
      increased [Ca2+]i and contractile responses in a dose-dependent manner in all
      groups. The vasopressin-induced change in [Ca2+]i was significantly greater in 5-
      and 17-week-old SHR than in age-matched controls. The sensitivity of [Ca2+]i to
      vasopressin was increased in adult SHR compared with WKY rats (pD2 9.0 +/- 0.1 in
      SHR, 8.2 +/- 0.3 in WKY rats). Vasopressin-stimulated contractile responses were
      increased in adult SHR. The endothelin-1-induced change in [Ca2+]i did not differ
      between WKY rats and SHR. The contractility of vessels in response to endothelin
      1 infusion was similar in age-matched groups. CONCLUSIONS: Endothelin-1-induced
      changes in [Ca2+]i and contractile responses in small arteries are similar in age
      matched WKY rats and SHR, whereas responses to vasopressin are significantly
      enhanced in SHR compared with WKY rats. Thus [Ca2+]i signalling for vasopressin
      is more active than is that for endothelin-1. Vasopressin but not endothelin-1
      might play a role in the development of hypertension in SHR.

PMID- 8884554
TI  - Some pharmacological and elastic characteristics of isolated subcutaneous small
      arteries from patients with essential hypertension.
AB  - OBJECTIVE: To investigate the elastic characteristics of the wall of isolated
      subcutaneous resistance arteries from patients with essential hypertension, the
      response of the vessels to endothelium-dependent and -independent vasodilators
      and the dependence on calcium. METHODS: Subcutaneous resistance arteries were
      isolated from 16 patients with never-treated essential hypertension and from 16
      normotensive controls matched for age and sex. The vessels were mounted in a
      myograph for isometric force development. The passive elastic characteristics
      were determined and then the response to acetylcholine, nitroprusside,
      felodipine, caffeine and calcium (in the presence of noradrenaline and prazosin
      or yohimbine) were determined. RESULTS: Young's elastic modulus as a function of
      wall stress was similar in the two groups of vessels. The relaxation of vessels
      from hypertensive and normotensive in response to acetylcholine, nitroprusside
      and felodipine was also similar. However, the response to caffeine was increased
      in vessels from the hypertensive patients, although the relationship between the
      dependence on the effect of calcium on the behaviour of arteries from
      hypertensives and controls was similar in the presence of prazosin and yohimbine.
      CONCLUSIONS: The altered morphology of subcutaneous resistance arteries from
      hypertensives is not caused by a change in the elastic characteristics of the
      wall material. The data support our previous observation of abnormal calcium
      handling in vessels from hypertensives, although they do not support the
      hypothesis that a generalized abnormality in endothelium-dependent or endothelium
      independent relaxation is of importance in essential hypertension.

PMID- 8884555
TI  - Responses of internal mammary artery graft flow to nitroprusside: a duplex
      Doppler study in hypertensive hearts.
AB  - OBJECTIVE: To assess the response of internal mammary artery (IMA) flow of
      hypertensive hearts to nitroprusside infusion. METHODS: Fifteen patients were
      studied with a high-frequency duplex Doppler probe from the supraclavicolar
      approach. All the patients had undergone coronary artery bypass surgery with an
      IMA graft into the left anterior descending artery. The investigated patients
      were normotensives (controls, n = 5) and hypertensive with a normal (group 1, n =
      5) or a hypertrophic (group 2, n = 5) left ventricle. Values of the left
      ventricular mass index were 102 +/- 11 g/m2 in controls, 115 +/- 18 g/m2 in group
      1 and 153 +/- 8 g/m2 in group 2. The IMA flow volume was studied at baseline and
      continuously during nitroprusside infusion. The arterial blood pressure was
      measured each minute by a cuff sphygmomanometer. In each patient we considered
      the peak flow volume (percentage increment from baseline) and the flow volume at
      the end point (the lowest tolerated diastolic blood pressure). RESULTS:
      Nitroprusside infusion induced a comparable flow-volume increment in controls (38
      +/- 27%) and in group 1 (24 +/- 11%). Conversely, the flow-volume increment was
      trivial in group 2 (6 +/- 6%). At the end point, the flow volume was similar to
      the baseline value in controls (with diastolic blood pressure 67 +/- 9 mmHg) and
      in group 1 (diastolic blood pressure 61 +/- 4 mmHg), whereas the flow volume
      declined significantly from baseline (by 23%) in group 2 at a perfusion pressure
      of 79 +/- 9 mmHg. CONCLUSION: Hypertensive patients with a normal left
      ventricular mass exhibit a coronary flow behaviour similar to that of
      normotensives in response to a nitroprusside infusion. Conversely, hypertrophic
      hypertensives show a blunted nitroprusside-induced coronary vasodilator response
      and are much more vulnerable to coronary flow reductions in the face of
      hypotension. This dynamic assessment of flow patterns can be obtained non
      invasively by duplex Doppler monitoring of IMA graft flow.

PMID- 8884556
TI  - Echocardiography overestimates left ventricular mass: a comparative study with
      magnetic resonance imaging in patients with hypertension.
AB  - OBJECTIVE: To compare measurement of left ventricular mass (LVM) by M-mode
      echocardiography and magnetic resonance imaging (MRI) in hypertensive subjects.
      DESIGN: A prospective study. SUBJECTS: Twenty-four untreated hypertensive
      patients [19 men and five women, aged 51 +/- 2 (mean +/- SEM) years, supine blood
      pressure 159/101 +/- 3/1 mmHg]. SETTING: The Blood Pressure Unit, St Georges
      Hospital Medical School and Magnetic Resonance Unit, Royal Brompton National
      Heart and Lung Hospital, London. MAIN OUTCOME MEASURES: LVM estimated both by M
      mode echocardiography and by MRI. RESULTS: Using three standard M-mode formulae,
      widely different values of LVM were obtained with echocardiography [American
      Society of Echocardiography (ASE) 319 +/- 21 g, Penn 273 +/- 19 g. Teichholz 191
      +/- 11 g]. By MRI, the LVM was 232 +/- 11 g. The differences between MRI and
      echocardiography could not be explained in terms of the timing of measurements in
      the cardiac cycle. When single-slice MRI measurements at the appropriate level
      were applied to the ASE and Penn formulae, the LVM was again overestimated.
      CONCLUSION: Our study has shown major differences in LVM estimated using methods
      based on one-dimensional (echocardiography) compared with three-dimensional (MRI)
      data. These differences seem to be largely the result of the geometrical
      assumptions on which M-mode measurements are based. Our findings have important
      clinical implications for the assessment of the severity and response to
      treatment of left ventricular hypertrophy in hypertensive patients.

PMID- 8884557
TI  - Endocardial versus midwall measurement of left ventricular function in mild
      hypertension: an insight from the Harvest Study.
AB  - OBJECTIVE: To compare endocardial and midwall measurement of left ventricular
      fractional shortening in assessing cardiac systolic function in hypertension.
      SETTING: Seventeen hypertension clinics in northeast Italy. MAIN OUTCOME
      MEASURES: Left ventricular endocardial fractional shorteningcircumferential
      stress relationship versus midwall shortening-stress relationship in the subjects
      divided according to relative wall thickness (RWT) and left ventricular mass
      indexed by body surface area. PATIENTS: Borderline-to-mild hypertensives [n =
      635, aged 33 +/- 0.3 years (mean +/- SEM), office blood pressure 146 +/- 0.4/94
      +/- 0.2 mmHg (means +/- SEM)] in the Harvest Study and 50 normotensive controls
      with similar age and sex distributions. METHODS: Blood pressure was measured by
      24 h ambulatory monitoring. Left ventricular dimensional and functional indices
      were assessed by M-mode echocardiography. RESULTS: In the subjects divided into
      quintiles of RWT, the left ventricular shortening-stress relationship was
      increased in a parallel fashion when calculated by endocardial and by midwall
      measurements for RWT < or = 0.35. Instead, for greater RWT values (> or = 0.37)
      endocardial measurement constantly gave large values than did midwall
      measurement. Both the endocardial and the midwall shortening-stress relationships
      progressively decreased with increasing RWT. However, the endocardial shortening
      stress relationship remained greater than normal at any RWT, whereas the midwall
      shortening-stress relationship was decreased for RWT > or = 0.37. In a multiple
      regression analysis RWT was the most potent predictor of the endocardialmidwall
      shortening difference, left ventricular mass and 24 h systolic blood pressure
      being the second and third most potent predictors. CONCLUSIONS: We found a
      parallel increase in indices of cavity emptying and of myocardial contractility
      in mild hypertensive subjects with normal left ventricular geometry. When the RWT
      is increased, ejection phase indices may be normal in the presence of decreased
      myocardial contractility.

PMID- 8884558
TI  - Arterial blood pressure and left ventricular hypertrophy in haemodialysis
      patients.
AB  - OBJECTIVE: To test the hypothesis that there is an association between arterial
      blood pressure and left ventricular hypertrophy and patterns of ventricular
      geometry, defined echocardiographically, in a group of stable haemodialysis
      patients with a low prevalence of extrarenal diseases. DESIGN AND METHODS:
      Patients with end-stage renal failure treated by regular haemodialysis (aged 44.3
      +/- 12.9 years, n = 103, among whom 52 men and 23 blacks, dialysis duration 49.8
      +/- 35.3 months) were subjected to echocardiographic evaluation (M-mode,
      bidimensional and Doppler) on the day preceding dialysis. The average of all
      predialysis blood pressure determinations during the 3 months preceding the tests
      (34-38 determinations in each patient) were used as baseline data. Univariate and
      multivariate tests were used to assess the main variables associated with
      echocardiographically defined cardiac alterations and with patterns of
      ventricular geometry. RESULTS: The systolic blood pressure was significantly
      associated with the left ventricular mass index and was significantly and
      independently correlated with left ventricular hypertrophy, posterior wall
      hypertrophy, left ventricle dilation and increased relative wall thickness. Other
      significant correlations were between the haematocrit level and left ventricular
      hypertrophy and between age and altered systolic and diastolic functions.
      Concentric ventricular hypertrophy was observed only in patients with a history
      of hypertension, whereas the prevalence of normal geometry was higher in patients
      without a history of hypertension. CONCLUSION: The systolic blood pressure is an
      important factor influencing the occurrence of left ventricular hypertrophy in
      haemodialysis patients and also affects the left ventricle geometry in this
      population.

PMID- 8884559
TI  - Plasma renin activity levels influence the effect of converting enzyme inhibitors
      in preserving renal function in hypertension.
AB  - OBJECTIVE: To study the effect of treatment with cilazapril versus nifedipine on
      the glomerular filtration rate (GFR), microalbumin excretion rate (mu Alb) and
      baseline plasma renin activity (PRA) levels in non-diabetic or diabetic essential
      hypertension. DESIGN AND METHODS: Thirty-four moderate essential hypertensives
      and thirty-two type II diabetic hypertensives with currently normal renal
      function completed the study, receiving treatment with a converting enzyme
      inhibitor (CEI, 5-10 mg/day cilazapril) or a non-CEI (20-40 mg slow-release
      nifedipine three times a day) during a 12-month controlled follow-up study.
      RESULTS: Either treatment induced a similar reduction in blood pressure. Patients
      with PRA > 3 ng/ml per h treated with cilazapril showed a proportional increase
      in GFR, whereas in those treated with a non-CEI there was a decline in GFR after
      8 and 12 months. Only diabetic patients treated with cilazapril showed a mu Alb
      reduction associated with a stable GFR. CONCLUSION: PRA predicts the effect of
      CEI preserving renal function in essential and diabetic hypertension.

PMID- 8884560
TI  - Clinical and biochemical criteria in the detection of renal artery stenosis.
AB  - OBJECTIVE: To investigate methods to diagnose renal artery stenosis (RAS) among
      the general hypertensive population. METHODS: We studied the value of clinical
      and biochemical characteristics at the outpatient clinic to identify subjects
      with a renal artery narrowing of more than 50% of the luminal surface among 1047
      hypertensive patients. Included in the analysis were: blood pressure, age, sex,
      body mass index, endogeneous creatinine clearance, smoking and plasma renin
      activity. RESULTS: Among the 1047 patients, 355 were selected for angiography. In
      this subgroup 104 patients (29%) had RAS. The subjects with RAS had significantly
      higher diastolic and systolic blood pressures than did those without stenosis.
      Forward stepwise logistical regression analysis showed that systolic blood
      pressure, stimulated plasma renin activity and smoking were the most predictive
      independent screening variables for the presence of RAS. Yet, none of these
      characteristics or their combinations were sufficiently sensitive to distinguish
      reliably between patients with essential hypertension and those with RAS. Sytolic
      blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg on automatic
      (Dinamap) recording as criteria selected a subgroup of patients with a RAS
      prevalence of 30%. CONCLUSIONS: By using blood pressure screening criteria a
      subgroup of hypertensive patients with a high prevalence of RAS can be formed in
      whom further invasive tests for RAS are indicated and efficient.

PMID- 8884561
TI  - Oedema formation with the vasodilators nifedipine and diazoxide: direct local
      effect or sodium retention?
AB  - OBJECTIVE: To determine whether the common side effect of ankle oedema with
      arteriolar vasodilators such as the calcium entry blocker (CEB) nifedipine and
      the potassium channel opener (PCO) diazoxide is the direct result of peripheral
      vasodilation or merely a consequence of renal sodium retention. DESIGN: In 12
      healthy sitting volunteers we studied for 3 h the effects of 20 mg nifedipine,
      150 mg diazoxide intravenously, 25 mg captopril and placebo on oedema formation
      and sodium excretion. CONCLUSIONS: Foot swelling was determined with a new
      accurate device (coefficient of variation 0.30%), which uses Archimedes principle
      to measure water displacement induced by immersion of the foot. Blood pressures
      were recorded with a Hawksley random-zero sphygmomanometer. RESULTS: All of the
      active drugs decreased diastolic blood pressure (captopril by 9 +/- 2%,
      nifedipine by 4 +/- 3% and diazoxide by 2 +/- 2%, compared with an increase of 5
      +/- 2% with placebo). Foot volume increased acutely after administration of
      nifedipine (by 2.6 +/- 0.4%), whereas it remained stable with placebo and the
      other drugs. Administration of captopril and nifedipine induced increases of
      fractional sodium excretion (by 20 +/- 9% and 40 +/- 20%, respectively) in
      contrast to the decreases with placebo and diazoxide (by 13 +/- 11% and 24 +/-
      10%, respectively). Only administration of nifedipine induced significant, albeit
      small, increases in haemoglobin and serum albumin levels. CONCLUSIONS:
      Administration of nifedipine increased foot volume and natriuresis
      simultaneously, thereby supporting the hypothesis that development of ankle
      oedema with CEB is a local phenomenon at the site of vasodilation. The absence of
      a similar increase in foot volume with diazoxide administration should be
      interpreted with caution because of the rather minor effect of this dose of
      diazoxide on blood pressure. However, it could be indicative of a different
      mechanism of oedema formation with PCO.

PMID- 8884562
TI  - Screening 'white-coat' hypertension with an anxiolytic agent.

PMID- 8884564
TI  - Genetic screening, testing and treatment: how far can we go?
AB  - Treatment comes in three forms: care, control, cure; each will be part of any new
      development in the management of genetic disease, either Mendelian or complex.
      Diagnosis recognizes three states of disease: impairment, disability, and
      handicap when the disease is symptomatic and has manifestations. Genetics in
      health care has the potential to prevent these manifestations by interventions at
      the presymptomatic stage. Wherever cause of disease involves genotypic variation
      that undermines homeostasis, genetic testing and screening could play a
      predictive role. The area of greatest interest will be the common multifactorial
      diseases. While some persons worry that geneticists have taken society too fast
      and far along the road to ruin, it is closer to the truth that we have actually
      gone rather slowly and not very far along the road to better personal and
      collective health. With wisdom and caution the new opportunities for genetic
      testing or screening will become part of health care; and sooner rather than
      later when better treatments for our inherited infirmities are found.

PMID- 8884563
TI  - Abnormal cholesterol biosynthesis in sitosterolaemia and the Smith-Lemli-Opitz
      syndrome.
AB  - We investigated the enzyme defects in two inherited disorders of cholesterol
      biosynthesis: sitosterolaemia and the Smith-Lemli-Opitz syndrome. In
      sitosterolaemic homozygotes, plasma plant sterols (sitosterol and campesterol)
      concentrations are elevated because of enhanced intestinal absorption and
      diminished removal. Underlying these changes is very low cholesterol biosynthesis
      to provide extra sterol for cell growth. Extremely reduced activities of HMG-CoA
      reductase, the rate-controlling enzyme for cholesterol biosynthesis, caused by
      deficient HMG-CoA reductase mRNA is responsible and is the suspected inherited
      abnormality. The Smith-Lemli-Opitz syndrome is caused by a block in the last
      reaction in the cholesterol biosynthetic pathway, the conversion of 7
      dehydrocholesterol to cholesterol, which is catalysed by 7-dehydrocholesterol
      delta 7-reductase. As a result, low plasma and tissue cholesterol with high 7
      dehydrocholesterol levels are found in homozygotes, who show characteristic
      phenotypes of mental retardation, facial dysmorphism, and organ and limb
      congenital anomalies. Similar biochemical findings are produced in rats fed BM
      15,766, an inhibitor of 7-dehydrocholesterol delta 7-reductase. Interestingly,
      feeding cholesterol can suppress abnormal cholesterol biosynthesis and improve
      symptoms in homozygotes and rats fed BM 15,766.

PMID- 8884566
TI  - Ethical reflections concerning genetic services. A paradigm for the future?

PMID- 8884565
TI  - Somatic gene therapy for phenylketonuria and other hepatic deficiencies.
AB  - Gene therapy is the delivery of genetic material to specific cell types of an
      organism to alter its physiology or function. This technology is being explored
      as a means of treating diseases caused by deficiencies of hepatic gene products.
      The two diseases being used as models for hepatic gene therapy are classical
      phenylketonuria (PKU) and haemophilia B. Vectors derived from adenoviruses can be
      used to completely correct these diseases in animal models. The phenotypic
      correction generated in these studies is transient, and cannot be duplicated by
      vector readministration. The transient nature of transgene expression results
      from the destruction of the virally-transduced cells by a cellular immune
      response directed against the late viral gene products that are also expressed in
      the target cells. The inability to repeatedly administer virus is caused by a
      humoral immune response directed against viral proteins present at the time of
      infusion. If the host immune response is suppressed, transgene expression can
      persist for 6 months or more. These findings suggest that host immunomodulation
      in combination with further modification of the adenoviral vector to reduce or
      eliminate late viral gene expression may permit long-term expression of
      potentially therapeutic gene products in mammalian liver.

PMID- 8884567
TI  - Metabolic fuel utilization and pyruvate oxidation during the postnatal period.
AB  - The transplacental supply of nutrients is interrupted at birth, which diverts
      maternal metabolism to lactation. After birth, energy homeostasis is rapidly
      regained through milk nutrients which supply the newborn with the fatty acids and
      ketone bodies required for neonatal development. However, immediately after birth
      and before the onset of suckling there is a time lapse in which the newborn
      undergoes a unique kind of starvation. During this period glucose is scarce and
      ketone bodies are not available owing to the delay in ketogenesis. Under these
      circumstances, the newborn is supplied with another metabolic fuel, lactate,
      which is utilized as a source of energy and carbon skeletons. Neonatal rat lung,
      heart, liver and brain utilize lactate for energy production and lipogenesis.
      Lactate is also utilized by the brain of human babies with type I glycogenosis.
      Both rat neurons and astrocytes in primary culture actively use lactate as an
      oxidizable substrate and as a precursor of phospholipids and sterols. Lactate
      oxidation is enhanced by dichloroacetate, an inhibitor of the pyruvate
      dehydrogenase kinase in neurons but not in astrocytes, suggesting that the
      pyruvate dehydrogenase is regulated differently in each type of cell. Despite the
      low activity of this enzyme in newborn brain, pyruvate decarboxylation is the
      main fate of glucose in both neurons and astrocytes. The occurrence of a yeast
      like pyruvate decarboxylase activity in neonatal brain may explain these results.

PMID- 8884568
TI  - Regulation and function of the mitochondrial genome.
AB  - Molecular changes in human mitochondrial DNA play a significant role in causing
      certain human diseases. Mitochondrial DNA mutations range from single base pair
      changes in the 16.5 kilobase pair genome up to large deletions and
      rearrangements. This report summarizes the current overall understanding of the
      mode and mechanism of mitochondrial DNA replication and transcription, and how
      this relates to mitochondrial gene expression, which is essential for cellular
      energy production and organelle biogenesis. Special attention is given to recent
      findings that bear on early steps in the process of transcription and, in turn,
      the consequences for initiating DNA replication.

PMID- 8884569
TI  - Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex.
AB  - The most common defect associated with deficiency of the pyruvate dehydrogenase
      (PDH) complex occurs in the E1 component, specifically due to mutations in the X
      linked E1 alpha gene. Clinical sequelae of these mutations, which range from
      severe neonatal lactic acidosis to carbohydrate-sensitive ataxia, can be
      different in males and females depending on the nature of the mutation and, in
      the case of females, on the X-inactivation pattern in different tissues. Males
      have a high representation of missense mutations among the patient cohort, while
      females are much more likely to have DNA rearrangements, particularly toward the
      3' end of the coding sequence of the gene. Missplicing mutations involving exon 6
      deletion have been reported, as has a missense mutation conferring true thiamin
      responsiveness of the enzyme and the patient's clinical symptoms. Pyruvate
      carboxylase deficiency, on the other hand, is a true autosomal recessive disease,
      though it has high occurrences in particular ethnic groups, especially in
      Algonkian-speaking Amerindians and in Arabs. In the former group the defect is a
      simple type in which material cross-reactive to pyruvate carboxylase antibody is
      present in cultured cells (CRM+ve). In the latter group, cross-reacting material
      is rarely present (CRM-ve). The CRM+ve patients can survive into teenage years
      with careful supervision, while the CRM-ve patients have complications due to
      hyperammonaemia and dysfunction of the urea cycle and rarely survive beyond 3
      months of life.

PMID- 8884570
TI  - Disorders of the electron transport chain.
AB  - Defects in a pathway as complex as the electron transport chain cause a variety
      of clinical abnormalities, which vary from fatal lactic acidosis in infancy to
      mild muscle disease in adults. The primary defect may reside in the nucleus or
      the mitochondrial genome. Until relatively recently, biochemical assays were the
      definitive means of establishing a defect of the electron transport chain.
      However, identification of mtDNA abnormalities allows defects to be defined more
      precisely and in a number of cases provides an easier (more reliable) means of
      investigation. Despite advances in this field, disorders of the electron
      transport chain still remain underdiagnosed. This review attempts to provide a
      general outline of the biochemistry and molecular genetics associated with these
      disorders and some of the factors involved in establishing a diagnosis in those
      patients with a suspected defect of the electron transport chain.

PMID- 8884571
TI  - Disorders of gluconeogenesis.
AB  - Gluconeogenesis, or the formation of glucose from mainly lactate/ pyruvate,
      glycerol and alanine, plays an essential role in the maintenance of
      normoglycaemia during fasting. Inborn deficiencies are known of each of the four
      enzymes of the glycolytic-gluconeogenic pathway that ensure a unidirectional flux
      from pyruvate to glucose: pyruvate carboxylase, phosphoenolpyruvate
      carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase. In this
      paper, the clinical picture, pathophysiology, diagnostic tests, genetics,
      treatment and prognosis of the deficiencies of fructose-1,6-bisphosphatase and
      phosphoenolpyruvate carboxykinase are reviewed.

PMID- 8884572
TI  - Metabolic intermediates in lactic acidosis: compounds, samples and
      interpretation.
AB  - A number of acquired conditions including infections, severe catabolic states,
      tissue anoxia, severe dehydration and poisoning can give rise to
      hyperlactacidaemia. All these causes should be ruled out before considering
      inborn errors of metabolism. Carefully collected samples are necessary if
      artefacts that result in spuriously increased lactate/pyruvate (L/P) and 3
      hydroxybutyrate/acetoacetate (B/A) ratios are to be avoided. When properly
      performed, 24-h studies of L/P and B/A ratios provide a useful tool in making a
      diagnosis. A few metabolic profiles when present are specific or highly
      suggestive of a given disorder. When the L/P ratio is normal or low, pyruvate
      dehydrogenase (PDH) deficiency is highly probable whatever the lactate
      concentration, which is often only moderately elevated after meal, may be. When
      the L/P ratio is very high in association with post-prandial hyperketonaemia and
      in contrast to a normal or low B/A ratio, pyruvate carboxylase (PC) deficiency
      and alpha-ketoglutarate dehydrogenase (KGDH) deficiency are the most likely
      diagnoses. The distinction between the two disorders relies upon amino acid and
      organic acid profiles (glutamate and alpha-ketoglutarate accumulations in KGDH
      deficiency and hyperammonaemia and hypercitrullinaemia in PC deficiency). When
      both L/P and B/A ratios are elevated and associated with significant post
      prandial hyperketonaemia, respiratory-chain disorders should first be suspected.
      All other profiles, especially a high L/P ratio without hyperketonaemia, are
      compatible with respiratory-chain disorders but are not specific; all acquired
      anoxic conditions should also be ruled out. Clearly, the clinical utility of
      these profiles needs to be interpreted cautiously in very ill patients in
      relation to the cardiocirculatory condition and to therapy. Finally, a normal
      profile, even after stress and loading, does not rule out an inborn error of
      lactate/pyruvate oxidation.

PMID- 8884573
TI  - Mitochondrial encephalomyopathies: what next?
AB  - In few areas of medicine has progress been more spectacular than in the field of
      mitochondrial diseases, especially those related to mtDNA mutations. Much remains
      to be done, however, and this brief review discusses the following areas of
      research where progress has been more limited or data are still controversial:
      (1) the molecular basis of respiratory-chain defects due to nuclear DNA
      mutations; (2) defects of mitochondrial protein importation; (3) defects of
      intergenomic signalling; (4) pathophysiology of mtDNA-related disorders; (5)
      ageing and age-related neurodegenerative diseases; (6) therapy; and (7) genetic
      counselling.

PMID- 8884574
TI  - Neurological presentations of mitochondrial diseases.
AB  - We present here a report on a 5-year experience in clinical investigation,
      diagnostic management and molecular genetic studies of neuromitochondrial
      disorders, defined on the basis of morphological, biochemical and genetic
      findings. Leigh disease is the most frequent clinical presentation in infancy and
      childhood, but symptoms at onset are poorly informative. In paediatric cases,
      lactic acidosis and neuroradiological abnormalities are frequent, and can be of
      help for the diagnostic orientation. In the adult population, muscle weakness,
      ophthalmoplegia with ragged-red fibres, retinitis pigmentosa, progressive
      myoclonal ataxia, and early-onset stroke-like episodes, are frequently combined
      in complex syndromes that are often familial (maternally inherited) and/or
      associated with well-established mutations in mitochondrial DNA (mtDNA). However,
      the presence of overlap syndromes and features common to many neuromitochondrial
      diseases can complicate the clinical evaluation and the diagnostic approach. The
      pathogenicity of a given mtDNA mutation can frequently be ascertained by
      correlating the degree of heteroplasmy with the clinical or biochemical
      phenotypes. Moreover, transmitochondrial cybrids can be used to test the effects
      of either mitochondrial or nuclear gene abnormalities in a fully controlled, user
      friendly and highly informative system.

PMID- 8884575
TI  - Clinical presentation of mitochondrial disorders in childhood.
AB  - Respiratory-chain deficiencies have long been regarded as neuromuscular diseases.
      In fact, oxidative phosphorylation, i.e. adenosine triphosphate (ATP) synthesis
      by the respiratory chain, does not occur only in the neuromuscular system.
      Indeed, a number of non-neuromuscular organs and tissues are dependent upon
      mitochondrial energy supply. For this reason, a respiratory chain deficiency can
      theoretically give rise to any symptom, in any organ or tissue, at any age and
      with any mode of inheritance, owing to the twofold genetic origin of respiratory
      enzymes (nuclear DNA and mitochondrial DNA, mtDNA). In recent years, it has
      become increasingly clear that genetic defects of oxidative phosphorylation
      account for a large variety of clinical symptoms in childhood. Among 100 patients
      with respiratory-chain deficiencies identified in our centre, 56% presented with
      a non-neuromuscular symptom and 44% were referred for a neuromuscular problem. It
      appears that the diagnosis of a respiratory-chain deficiency is difficult
      initially when only one symptom is present. In contrast, this diagnosis is easier
      to consider when two seemingly unrelated symptoms are observed.

PMID- 8884576
TI  - Morphological studies of skeletal muscle in lactic acidosis.
AB  - This paper underscores the contribution of routine morphological examination of
      skeletal muscle in patients with lactic acidosis. Mitochondrial disorders are by
      far the most common causes of primary lactic acidosis, in which muscle biopsy
      analysis helps in diagnosis and in the search for the molecular anomalies. Thus,
      we focus our attention on one particular point: the contribution of the
      morphological study of muscle biopsy in primary lactic acidosis due to
      mitochondrial disorders, especially mitochondrial respiratory-chain diseases.

PMID- 8884577
TI  - Magnetic resonance imaging in lactic acidosis.
AB  - Mitochondrial defects, defects in gluconeogenesis, and biotin-responsive multiple
      carboxylase deficiency are disorders characterized by primary lactic acidosis. In
      this review, characteristic findings in magnetic resonance imaging (MRI) of the
      brain, as related to histopathological abnormalities, are described for the
      different disorders and the diagnostic value of the MRI findings is discussed.
      Inborn errors of metabolism with primary lactic acidosis should be considered in
      particular when MRI shows lesions similar to or reminiscent of effects of focal
      or generalized hypoxia-ischaemia, or when MRI shows signs of chronic
      neurodegeneration, but rarely in cases with predominantly white-matter changes.

PMID- 8884578
TI  - The role of magnetic resonance spectroscopy in the investigation of lactic
      acidosis and inborn errors of energy metabolism.
AB  - Magnetic resonance spectroscopy (MRS) provides a non-invasive method of
      investigating disordered energy metabolism in vivo. Here, we briefly outline some
      MRS studies of skeletal muscle and brain metabolism that have been carried out in
      patients with inborn errors of energy metabolism. We concentrate in particular on
      the use of 1H MRS for the detection of elevated brain lactate in these patients.

PMID- 8884580
TI  - The treatment of congenital lactic acidoses.
AB  - Congenital lactic acidoses form a heterogeneous group of disorders: this paper
      considers primarily defects of the pyruvate dehydrogenase complex and the
      respiratory chain. Attempts to treat these disorders are hampered by uncertainty
      concerning the pathophysiology and by the central role of the enzymes in cellular
      metabolism. Few strategies are of proven efficacy, though many have been tried,
      including dietary manipulation, enhancement of residual enzyme activity,
      artificial electron acceptors and free-radical scavengers. Evaluation of
      treatment is complicated by the rarity, heterogeneity and unpredictable course of
      the diseases. Double-blind placebo-controlled trials are needed.

PMID- 8884579
TI  - Neuropathology and pathogenesis of mitochondrial diseases.
AB  - The majority of patients with mitochondrial disease have significant
      neuropathology, with the most common features being spongiform degeneration,
      neuronal loss and gliosis. Although there is considerable overlap between
      different mitochondrial diseases, the nature and distribution of the lesions is
      sufficiently distinctive in some cases to suggest a specific diagnosis. On the
      other hand, a number of different defects in cerebral energy metabolism are
      associated with common patterns of neuropathology (e.g. Leigh syndrome),
      suggesting that there is a limited range of responses to this type of metabolic
      disturbance. There are many descriptions of neuropathological changes in patients
      with mitochondrial disease, but there has been remarkably little investigation of
      the underlying pathogenic mechanisms. Comparisons with other conditions of
      cerebral energy deprivation such as ischaemia/hypoxia and hypoglycaemia suggest a
      possible role for excitotoxicity initiated by excitatory amino acid
      neurotransmitters. An additional contributing factor may be peroxynitrite, which
      is formed from nitric oxide and the oxygen free radicals which accumulate with
      defects of the mitochondrial electron transport chain. Mitochondrial diseases are
      often characterized by episodes of neurological dysfunction precipitated by
      intercurrent illness. Depending on the severity of the metabolic abnormality,
      each of these episodes carries a risk of further neuronal death and the result is
      usually progressive accumulation of irreversible damage. The balance between
      reversible functional impairment and neuronal death during episodes of metabolic
      imbalance is determined by the effectiveness of various protective mechanisms
      which may act to limit the damage. These include protective metabolic shielding
      of neurons by astrocytes and suppression of electrical activity (and hence energy
      demands) by activation of ATP-gated ion channels. In addition, recent evidence
      suggests that lactic acid, the biochemical abnormality common to these
      conditions, may not be toxic at moderately high concentrations but may in fact be
      protective by reducing the sensitivity of neurons to excitotoxic mechanisms.

PMID- 8884581
TI  - Genetic counselling and prenatal diagnosis in disorders of the mitochondrial
      energy metabolism.
AB  - Point mutations in mitochondrial DNA, as found in MELAS, MERRF, NARP and other
      syndromes, are inherited via the maternal lineage. Genetic counselling can be
      beneficial, but prenatal diagnosis is not advantageous in these syndromes.
      Empirical data about the recurrence risk can be applied in Leber disease (LHON).
      Mitochondrial disorders not associated with a point mutation have a sporadic
      nature (large deletions/duplications in mitochondrial DNA) or are transmitted
      according to Mendelian laws. Autosomal dominant inheritance is likely to be found
      in disorders with depletion of mitochondrial DNA. X-linked mode of inheritance is
      seen in Menkes disease, Barth syndrome, and in deficiencies of the E1 alpha
      subunit of the pyruvate dehydrogenase complex. Mutation analysis or linkage
      studies can be applied for carrier detection and prenatal diagnosis in these
      three types of mitochondriopathies. The majority of the disorders with a
      disturbed mitochondrial energy metabolism are likely inherited in an autosomal
      recessive mode. Prenatal diagnosis can be performed in the cases of cytochrome c
      oxidase and NADH dehydrogenase deficiencies in chorionic villi in selected
      families.

PMID- 8884582
TI  - The effects of behavioural relaxation on cognitive performance in adults with
      severe intellectual disabilities.
AB  - Behavioural relaxation training has been found to be effective in the treatment
      of generalized anxiety in people with intellectual disability. The present study
      is designed to assess whether or not these techniques can help individuals in
      more generalized aspects of their life. Two groups of 10 adults with a severe
      intellectual disability formed a relaxation group and a control group. The
      relaxation group were given a course in behavioural relaxation training and the
      control group were given a quiet reading period for the same amount of time. Each
      subject was given a digit span test, a test of long-term memory and an incidental
      learning test after each session. Results suggest behavioural relaxation training
      has a beneficial effect on performance on tests of short-term memory and
      incidental learning, but no effect upon long-term memory.

PMID- 8884583
TI  - Increasing on-task behaviour through interruption-prompting.
AB  - This study was designed to assess the effects of response-contingent interruption
      prompting of stereotypic behaviour on on-task behaviour, inactivity and
      inappropriate behaviour. Also, the relationship between these behaviours was
      investigated. Five individuals with severe intellectual disability and autism
      participated. Data were collected within a reversal design. The results showed a
      statistically significant increase of on-task behaviour when interruption
      prompting of stereotypic behaviour was in effect. Inactivity was statistically
      related to inappropriate behaviour. In terms of the continuous effort to identify
      procedures that are least intrusive for the client to attain behaviour
      improvement, it is suggested that interruption-prompting of stereotypic behaviour
      may be a reasonable choice for practicians.

PMID- 8884584
TI  - Psychiatric disorder in Asian adults with learning disabilities: patterns of
      service use.
AB  - Asian and white Caucasian adults with learning disabilities seen by the
      Department of the Psychiatry of Learning Disabilities, Frith Hospital, Leicester,
      England, in 1991 were studied. Asian adults with learning disabilities were under
      represented with respect to the local population (as measured by learning
      disability register), but not the population of individuals with learning
      disabilities known to the psychiatric services. Asians were significantly more
      likely to receive a psychiatric diagnosis, in particular that of psychosis, but
      there were striking similarities in the routes of referral, the number of
      contacts with the service and the range of defined disabilities.

PMID- 8884585
TI  - Psychological stress in people with profound mental retardation.
AB  - Does emotional stress in people with profound mental retardation occur and does
      it result from simple stimuli of daily living? Can this be measured by recording
      vital signs? To obtain answers, the histories of stress and stress diseases, and
      the behavioral characteristics of 163 institutionalized adults with developmental
      disabilities were evaluated; vital signs, temperatures and bodily expressions of
      35 subjects from this sample were monitored. All but two of the 35 subjects had
      elevations of heart rate, blood pressure, respiration rate, core body
      temperature, and changes in peripheral temperature. Reactions occurred with
      unpleasant and pleasurable stimuli, and were greatest at clinical examinations
      and when the subjects were stared at. Responses were best demonstrated by heart
      rate, respiration rate, blood pressure and temperature. Such reactions result
      from the insecurity of people whose disabilities prevent them from adjusting to
      perceived threats.

PMID- 8884586
TI  - Behavioural changes in people with learning disability and dementia: a
      descriptive study.
AB  - The behaviour of 12 people with mild and more severe learning disability and
      dementia is described using Past Behavioural History Inventory (PBHI), an
      instrument devised for the description of behaviour in people of normal
      intelligence and dementia. The PBHI appears sensitive to behavioural changes. The
      behavioural changes are described and are similar to those seen in people without
      a learning disability. Carers were unaware of the behavioural changes associated
      with dementia. The behavioural changes could be used to assist in the earlier
      diagnosis and management of dementia in people with learning disability.

PMID- 8884587
TI  - Factors associated with the successful or unsuccessful withdrawal of
      antipsychotic drug therapy prescribed for people with learning disabilities.
AB  - Many published accounts of drug review programmes have reported reductions in the
      prescribing of psychotropic drugs prescribed for people with learning
      disabilities. Rarely though has the outcome for the patient been reported. The
      Leicestershire antipsychotic drug review programme resulted in antipsychotic drug
      dose reduction or withdrawal in 123 patients. Data relating to outcomes were
      analysed in order to identify factors associated with successful withdrawal. Few
      such factors were identified. The successful withdrawal of antipsychotic drug
      treatment (31 patients) was associated with low doses, predominantly of the drug
      thioridazine, minimal psychopathology, the presence of epilepsy, and the lack of
      hyperactivity, aggression of stereotypy.

PMID- 8884588
TI  - Ocular defects in children and adolescents with severe mental deficiency.
AB  - To assess the need for eye care in children and adolescents with severe mental
      deficiency, a cross-sectional study of the prevalence and causes of ocular
      defects amongst these individuals was conducted. Two hundred and sixty residents
      in a mental handicap unit were examined from January 1992 to June 1993. It was
      found that there was an unusually high prevalence of severe visual impairment
      (25%), refractive errors (24%), squint (8%) and a number of organic ocular
      diseases (8%). All the patients studied were non-verbal and 18% of them were
      deaf. Only 23 patients could walk. The results emphasize the need for
      establishing an efficient system to provide regular ophthalmic care for children
      with severe mental deficiency.

PMID- 8884589
TI  - Challenging behaviour: the effectiveness of specialist support teams.
AB  - Two specialist community services for people with learning disabilities and
      challenging behaviour were evaluated over approximately 3 years. Intervention
      effectiveness was assessed with respect to changes in subjects' skills,
      challenging behaviours, mental health and quality of life, and to changes in
      staff morale. Subjects assessed as having challenging behaviour but not referred
      for specialist input were also studied. Comparison of changes in referred and non
      referred samples over time showed minor differences only, indicating little
      intervention effect and demonstrating stability in the comparison sample.
      Analysis of the two services separately yielded different results. Positive
      client change was evident with respect to one service, whilst little change was
      noted with respect to the other. There was little evidence to suggest that either
      service had any effect on staff morale. Differences between the two services in
      terms of structure, staffing characteristics and operational policies are
      discussed as possible factors in the differential results obtained. A major issue
      raised by the study concerns the quality of settings from which the subjects were
      referred for specialist support. This is discussed as a factor which may limit
      the effectiveness of specialist input.

PMID- 8884590
TI  - Engagement and interaction: a comparison between supported employment and day
      service provision.
AB  - Work and non-work experiences of 16 adults with learning disabilities were
      compared. The results indicated that people spent significantly more of their
      time engaged in task-related activities during paid work than in non-work
      situations, where high levels of disengagement were observed. Interaction
      patterns varied considerably across conditions, people spending more of their
      time interacting with others in the non-work condition, possibly as a result of
      high levels of supervisory support from service staff. Differences were also
      observed in the direction of interaction, with clients more likely to initiate
      interactions in the non-work condition. A breakdown of who interactions occurred
      with revealed that clients tended to talk with supervisors more often than anyone
      else in the non-work condition. During work, clients tended to interact more
      often with their non-disabled co-workers, and a significant proportion of time
      was spent interacting with the public. The findings are discussed in relation to
      the relative success of the employment movement and suggestions for further
      research are made.

PMID- 8884591
TI  - A review of antipsychotic drugs prescribed for people with learning disabilities
      who live in Leicestershire.
AB  - Antipsychotic drugs are widely prescribed for people with learning disabilities
      to control challenging behaviour. Concern has been expressed that such
      prescribing is excessive, inappropriate and potentially harmful. A review of 198
      patients with learning disabilities resulted in agreement to reduce or withdraw
      antipsychotic drug therapy in 123 cases. The antipsychotic drug therapy was
      totally withdrawn in 43 cases and the dose reduced for the remaining 80. Out of
      the 43 patients who underwent total drug withdrawal, 31 remained off such therapy
      and 12 required represcribing within a 12-month period. Out of the remaining 80
      who underwent dose reduction, 40 suffered a deterioration in behaviour which
      resulted in some degree of dose increase, and 40, although maintained on a lower
      dose, neither achieved total withdrawal nor deteriorated to an extent that a dose
      increase was required.

PMID- 8884592
TI  - Further evaluation of the Dementia Questionnaire for Persons with Mental
      Retardation (DMR).
AB  - The provisional diagnostic criteria for the Dementia Questionnaire for Persons
      with Mental Retardation (DMR), developed during a prior study, were evaluated in
      a 5-year longitudinal follow-up of 33 elderly institutionalized persons, aged 70
      years and over, and 45 institutionalized persons with Down's syndrome, aged 35
      years and over, with no dementia in the diagnosis at initial evaluation. During
      the study period, dementia was diagnosed according to DSM-III-R criteria in five
      elderly subjects and five subjects with Down's syndrome, whereas a diagnosis of
      possible dementia was made in two elderly subjects and three subjects with Down's
      syndrome. A DMR diagnosis based on the criterion increase over time of the sum of
      cognitive scores (SCS) > or = 7 points and/or of the sum of social scores (SOS) >
      or = 5 points' resulted in a sensitivity of 100% for both groups and a
      specificity of 73% in the elderly sub-group and 75% in the sub-group with Down's
      syndrome, independent of the (premorbid) intellectual level. A diagnosis based on
      a single completion of the DMR, using available information on former performance
      levels, also produced favourable results in the present study. However, this
      diagnostic approach is certainly not recommended for studies of larger samples
      because of the use of different methods measuring functional levels and different
      standards for levels of intellectual disability.

PMID- 8884593
TI  - Practice guidelines for the clinical assessment and care management of
      Alzheimer's disease and other dementias among adults with intellectual
      disability. AAMR-IASSID Workgroup on Practice Guidelines for Care Management of
      Alzheimer's Disease among Adults with Intellectual Disability.
AB  - The AAMR/IASSID practice guidelines, developed by an international workgroup,
      provide guidance for stage-related care management of Alzheimer's disease, and
      suggestions for the training and education of carers, peers, clinicians and
      programme staff. The guidelines suggest a three-step intervention activity
      process, that includes: (1) recognizing changes; (2) conducting assessments and
      evaluations; and (3) instituting medical and care management. They also provide
      guidance for public policies that reflect a commitment for aggressive care of
      people with Alzheimers's disease and intellectual disability, and avoidance of
      institutionalization solely because of a diagnosis of dementia.

PMID- 8884594
TI  - Ca2+ bound to the high affinity divalent cation-binding site of actin enhances
      actophorin-induced depolymerization of muscle F-actin but inhibits actophorin
      induced depolymerization of Acanthamoeba F-actin.
AB  - The cation tightly bound to actin, Mg2+ or Ca2+, affects the ability of
      actophorin to accelerate depolymerization of filaments and bind to monomers of
      actin prepared from rabbit skeletal muscle and Acanthamoeba castellanii.
      Actophorin interacted similarly with muscle and Acanthamoeba Mg2(+)-F-actin but
      depolymerized muscle Mg2(+)-F-actin more efficiently. Muscle Ca2(+)-F-actin
      depolymerized about 5 times more rapidly than Mg2(+)-F-actin in the presence of
      actophorin but Acanthamoeba Ca2(+)-F-actin was highly resistant to actophorin.
      Muscle actin subunits dissociated more rapidly than Acanthamoeba actin subunits
      from copolymers of muscle and Acanthamoeba Ca2(+)-actin upon addition of
      actophorin although Acanthamoeba actin dissociated much more rapidly from
      copolymers than from its homopolymer. The Kd of the 1:1 complex between
      actophorin and monomeric actin was somewhat lower for muscle Mg2(+)-ATP-G-actin
      than for both Acanthamoeba Mg2(+)-ATP-G-actin and muscle Ca2(+)-ATP-G-actin. The
      data for the interactions of actophorin with Acanthamoeba Ca2(+)-ATP-G-actin or
      muscle and amoeba Mg2(+)- and Ca2(+)-ADP-G-actin were incompatible with the
      formation of 1:1 actin: actophorin complexes and, thus, Kd values could not be
      calculated. While it may not be surprising that actophorin would interact
      differently with Mg2(+)- and Ca2(+)-actin, it is unexpected that the nature of
      the tightly bound cation would have such dramatically opposite effects on the
      ability of actophorin to depolymerize muscle and Acanthamoeba F-actin.
      Differential severing by actophorin, with Acanthamoeba Ca2(+)-actin being almost
      totally resistant, is sufficient to explain the results but other possibilities
      cannot be ruled out.

PMID- 8884595
TI  - Morphological changes in the triads and sarcoplasmic reticulum of rat slow and
      fast muscle fibres following denervation and immobilization.
AB  - We observed the morphological features of the membrane systems (sarcoplasmic
      reticulum, transverse tubules and triads) involved with the excitation
      contraction coupling in rat soleus and extensor digitorum longus muscle following
      two disuse protocols: denervation and immobilization. The immobilized positions
      were: maximum dorsal flexor (soleus were stretched and extensor digitorum longus
      were shortened), maximum plantar flexor (soleus were shortened and extensor
      digitorum longus were stretched), and midway between the dorsal flexor and
      plantar flexor. The arrangement of the membrane systems was disordered following
      both disuse conditions. Increases in transverse tubule network were apparent;
      there were clearly more triads than in normal fibres, and pentadic and heptadic
      structures (i.e., a close approximation of two or three transverse tubule
      elements with three or four elements of terminal cisternae of sarcoplasmic
      reticulum) were frequently appeared following both denervation and
      immobilization. The most notable difference between the influence of denervation
      and immobilization on the membrane systems is the time at which the pentads and
      heptads appeared. They appeared much earlier (1 week after denervation) in
      denervated than in immobilized (3 or 4 weeks after immobilization) muscle fibres.
      On the other hand, the frequency of pentads and heptads is clearly related to the
      fibre type (significantly higher in extensor digitorum longus) and to extent of
      atrophy. The different influences of immobilization in each leg position suggest
      that disuse, but with neurotrophic factor(s), influences on the membrane systems
      were affected by sarcomere length, and the neurotrophic factor(s) and muscle
      activity were not always necessary to form new membrane systems in disuse
      skeletal muscle fibres.

PMID- 8884596
TI  - Adaptive range of myosin heavy chain expression in regenerating soleus is broader
      than in mature muscle.
AB  - In adult rat muscles experimentally exposed to various patterns of activation,
      expression of myosin heavy chain isoforms changes, but only within a certain
      adaptive range. It is characteristic and different in fast or slow muscles. This
      may be due either to different intrinsic properties of the myogenic cells of the
      two types of muscles or to extrinsic factors. To test these assumptions, either
      rat soleus or extensor digitorum longus muscles were injured and transplanted to
      the bed of the extensor digitorum longus muscle. They regenerated and were
      reinnervated by the extensor digitorum longus nerve. Expression of myosin heavy
      chain isoforms was demonstrated immunohistochemically and by in situ
      hybridization, and analysed by SDS-gel electrophoresis. Three months after cross
      transplantation, regenerated soleus expressed all adult myosin heavy chain
      isoforms, including the myosin heavy chain-2B. The latter was detected in about
      50% of muscle fibres and contributed about 10-20% of all myosin heavy chains. The
      same percentage of myosin heavy chain-2B was found in regenerated extensor
      digitorum longus. In this regard therefore, the adaptive range of the regenerated
      soleus muscle was not significantly different from that of the extensor digitorum
      longus regenerating under the same conditions. This indicates that restriction of
      the adaptive range in a mature soleus muscle is not due to intrinsic properties
      of its myogenic cells. It is probably imposed by an extrinsic factor leading to
      irreversible shut-down of individual myosin heavy chain genes. On the other hand,
      myosin heavy chain-1 expression was significantly greater in the regenerated
      soleus than in the extensor digitorum longus innervated by the same nerve. Myosin
      heavy chain-1 and myosin heavy chain-2B were co-expressed in some regenerated
      soleus muscle fibres.

PMID- 8884597
TI  - Dictyostelium discoideum myoJ: a member of a broadly defined myosin V class or a
      class XI unconventional myosin?
AB  - The simple eukaryote Dictyostelium discoideum contains at least 12 unconventional
      myosin genes. Here we report the characterization of one of these, myoJ, a gene
      initially identified through a physical mapping screen. The myoJ gene encodes a
      high molecular weight myosin, and analysis of the available deduced amino acid
      sequence reveals that it possesses six IQ motifs and sequences typical of alpha
      helical coiled coils in the tail region. Therefore, myoJ is predicted to exist as
      a dimer with up to 12 associated light chains (six per heavy chain). The 7.8 kb
      myoJ mRNA is expressed all throughout the life cycle of D. discoideum. The myoJ
      gene has been disrupted and a phenotypic analysis of the mutant cells initiated.
      Finally, phylogenetic analysis of the head region reveals that myoJ is most
      similar to two plant myosin genes, Arabidopsis MYA1 and MYA2, that have been
      alternatively suggested to be either members of the myosin V class or founding
      members of the myosin XI class.

PMID- 8884598
TI  - Limits of titin extension in single cardiac myofibrils.
AB  - Passive force and dynamic stiffness were measured in relaxed, single myofibrils
      from rabbit ventricle over a wide range of sarcomere lengths, from approximately
      2-5 microns. Myofibril stretch up to sarcomere lengths of approximately 3 microns
      resulted in a steady increase in both force and stiffness. The shape of the
      length-force and the length-stiffness curves remained fully reproducible for
      repeated extensions to a sarcomere length of approximately 2.7 microns. Above
      this length, myofibrillar viscoelastic properties were apparently changed
      irreversibly, likely due to structural alterations within the titin (connectin)
      filaments. Stretch beyond approximately 3 microns sarcomere length resulted in a
      markedly reduced slope of the passive force curve, while the stiffness curve
      became flat. Thus, cardiac sarcomeres apparently reach a strain limit near a
      length of 3 microns. Above the strain limit, both curve types frequently showed a
      series of inflections, which we assumed to result from the disruption of titin
      thick filament bonds and consequent addition of previously bound A-band titin
      segments to the elastic I-band titin portion. Indeed, we confirmed in
      immunofluorescence microscopic studies, using a monoclonal antibody against titin
      near the A/I junction, that upon sarcomere stretch beyond the strain limit
      length, the previously stationary antibody epitopes suddenly moved into the I
      band, indicating A-band titin release. Altogether, the passive force/stiffness
      length relation of cardiac myofibrils was qualitatively similar to, but
      quantitatively different from, that reported for skeletal myofibrils. From these
      results, we inferred that cardiac myofibrils have an approximately two times
      greater relative I-band titin extensibility than skeletal myofibrils. This could
      hint at differences in the maximum passive force-bearing capacity of titin
      filaments in the two muscle types.

PMID- 8884599
TI  - Twitch characteristics and energy metabolites of mature muscle fibres of Xenopus
      laevis in culture.
AB  - Mature, high-oxidative, skeletal muscle fibres of Xenopus laevis were kept in
      culture in L-(Leibovitz's)-15 medium supplemented with creatine and antibiotics
      and some other additions. Single fibres were mounted at a fixed sarcomere length
      in a flow-through culture chamber which accommodates stimulus electrodes and a
      force transducer. Twitch characteristics were determined daily. Depending on
      culture conditions, fibres remained excitable electrically for up to two weeks at
      20 degrees C when foetal calf serum and/or phosphate were added to the culture
      medium. During the second week, fibres lost phosphocreatine and ATP, but
      relatively small changes (if any) in total creatine, glycogen and protein
      contents, fibre volume and dry weight occurred. Succinate dehydrogenase activity
      decreased after 9 days-when ATP was reduced already. Fibres which were
      inexcitable electrically contracted normally when exposed to caffeine, indicating
      that excitation-contraction coupling failed and that the contractile apparatus
      was still functional.

PMID- 8884600
TI  - Assembly of the cardiac I-band region of titin/connectin: expression of the
      cardiac-specific regions and their structural relation to the elastic segments.
AB  - The giant molecule titin (also called connectin) provides an elastic connection
      in the I-band between the Z-disk and A-band of striated muscle. This region is
      assembled in a tissue-specific way by extensive differential splicing events. We
      have raised monoclonal antibodies against the two N2-line isoforms of titin and
      demonstrate that both forms of cardiac I-band titin are constitutively co
      expressed in atrial and ventricular muscle. In developing mouse embryos, the
      expression of the cardiac N2-B isoform remains strictly cardiac-specific and is
      linked to the expression of the ubiquitous N2-A isoform. The mechanical function
      of the cardiac N2-line region was investigated ultrastructurally. Immunoelectron
      microscopy reveals that the N2-B region separates two mechanically distinct
      sections of titin with a hyperextensible segment spanning the distance to the Z
      disk. The formation of a plateau in the extension of cardiac titin rules out that
      Ig-domains can be unfolded as a mechanism of elasticity.

PMID- 8884601
TI  - Quantitative analysis of low molecular weight G-actin-binding proteins, cofilin,
      ADF and profilin, expressed in developing and degenerating chicken skeletal
      muscles.
AB  - A large amount of G-actin is pooled in the cytoplasm of young embryonic skeletal
      muscle and, although its concentration is reduced as muscle develops, the total
      amount of actin in muscle cells increases remarkably. Three G-actin-binding
      proteins, cofilin, ADF and profilin, are known to be involved in creating the G
      actin pool in the embryonic muscle. To better understand how they are responsible
      for the regulation of assembly and disassembly of actin in developing and
      degenerating muscles, we measured the amounts of the three G-actin-binding
      proteins by means of quantitative immunoblotting and compared them with that of G
      actin. The sum of the amounts of the three actin-binding proteins was
      insufficient at early developmental stages but sufficient at later stages to
      account for the pool of G-actin in young muscle cells. It decreased in parallel
      with the decrease in the G-actin pool as muscle developed. Expression of thymosin
      beta 4, which is known to be extremely important for G-actin-sequestering in a
      variety of non-muscle cells, was detected at a considerable level in young
      embryonic but not in adult skeletal muscles according to Northern and Western
      blotting. In degenerating denervated and dystrophic muscles, cofilin and
      profilin, but not ADF, were significantly increased in amount. From these
      results, we conclude that the G-actin pool in young embryonic skeletal muscle is
      mainly due to cofilin, ADF, profilin and thymosin beta 4, but thymosin beta 4 as
      well as ADF becomes less important as muscle develops. Cofilin and profilin may
      also be involved in the redistribution of actin during myofibrillogenesis and in
      the process of actin disassembly in degenerating muscles.

PMID- 8884602
TI  - Differential scanning calorimetric study of the complexes of modified myosin
      subfragment 1 with ADP and vanadate or beryllium fluoride.
AB  - The effects of various modifications of rabbit skeletal myosin subfragment 1 on
      the thermal denaturation of subfragment 1 in ternary complexes with Mg-ADP and
      orthovanadate (V1) or beryllium fluoride (BeFx) have been studied by differential
      scanning calorimetry. It has been shown that specific modifications of SH1 group
      of Cys-707 by different sulfhydryl reagents, trinitrophenylation of Lys-83, and
      reductive methylation of lysine residues promote the decomposition of the
      S1.ADP.Vi complex and change the character of structural transitions of the
      subfragment 1 molecule induced by the formation of this complex, but they have
      much less or no influence on subfragment 1 thermal stability in the S1.ADP.BeFx
      complex. Thus, the differential scanning calorimetric studies on modified
      subfragment 1 preparations reveal a significant difference between S1.ADP.Vi and
      S1.ADP.BeFx complexes. It is suggested that S1.ADP.Vi and S1.ADP.BeFx complexes
      represent structural analogues of different transition states of the ATPase
      cycle, namely the intermediate states S1**.ADP.Pi and S1*.ATP, respectively. It
      is also proposed that during formation of the S1.ADP.Vi complex the region
      containing both Cys-707 and Lys-83 plays an important role in the spread of
      conformational changes from the active site of subfragment 1 ATPase throughout
      the structure of the entire subfragment 1 molecule. In such a case, the effects
      of reductive methylation of lysine residues on the subfragment 1 structure in the
      S1.ADP.Vi complex are related to the modification of Lys-83.

PMID- 8884603
TI  - Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle
      subjected to stretch.
AB  - To ascertain if IGF-1 is a regulator of local muscle growth, total RNA was
      extracted from rabbit muscle induced to undergo rapid hypertrophy using active
      stretch and from control muscles. This was analysed by Northern hybridization
      with a 280 base pair probe containing sequences derived from exons 3 and 4 of the
      insulin-like growth factor 1 gene. Two types of insulin-like growth factor 1 mRNA
      were shown to be strong expressed in the stretched muscles. In situ hybridization
      using the same probe (280 base pair) showed that IGF-1 is strongly expressed in
      muscle that is induced to grow rapidly and is expressed in the muscle fibres
      themselves. Using RT-PCR a single insulin-like growth factor 1 isoform cDNA (IGF
      1Ea) could be cloned from the normal resting muscles. However, an additional
      isoform of insulin-like growth factor 1 (insulin-like growth factor 1Eb) was
      found to be expressed in stretched muscle undergoing hypertrophy. The E domain
      sequence of the additional isoform differs from the liver insulin-like growth
      factor 1Ea by the presence a 52 base pair insert. This changes the reading frame
      of the derived carboxyl-terminal resulting in a different precursor insulin-like
      growth factor 1 isoform. This insulin-like growth factor 1 mRNA probably encodes
      the precursor insulin-like growth factor 1 isoform that is responsible for local
      muscle growth regulation in response to mechanical stimulation. To confirm that
      alternative splicing of the insulin-like growth factor 1 gene occurs in muscle in
      response to physical activity, oligonucleotide primers were made which
      specifically amplify the cDNAs of two isoforms (insulin-like growth factors 1Ea
      and Eb) in the human as well as the rabbit. Following altered physical activity
      for 2 h to 6 days, appreciable levels of insulin-like growth factor 1Eb (in human
      the Ec) isoform were detected in skeletal muscle by using RT-PCR. In contrast
      very little if any of this splice variant could be detected in control muscle not
      subjected to stretch or extra physical activity.

PMID- 8884604
TI  - A simple method for automatic tracking of actin filaments in the motility assay.
AB  - A great deal of quantitative information about the actomyosin interaction can be
      obtained from the basic Kron and Spudich in vitro motility assay provided that
      care is taken to obtain consistency between experiments and that the data is
      examined comprehensively and not selectively. From observations of filament
      movement under a wide variety of conditions we have formulated the hypothesis
      that a large number of filaments moving over a short time period is
      indistinguishable from fewer filaments moving over a longer sequence of frames.
      This has been used to devise a simple automation of filament detection
      procedures. A sequence of images is digitized through a frame-grabber. If
      successive pairs of frames are compared the program will search for and detect
      the new position of every filament and show its vector on screen. Velocity is
      calculated and shown as a frequency histogram. The program regularly detects over
      100 filaments moving in each pair of frames; usually a sequence of up to 15 pairs
      of frames are studied yielding 500-1000 vectors in total. The algorithm cannot
      deal with filaments that meet, cross or divide, however, when filaments are
      moving less than 2 microns between frames this is only a small proportion of the
      whole. The program outputs fraction of filaments motile, mean velocity with
      standard deviation and density of filaments (filaments microns-2). A cumulative
      frequency histogram gives an immediate visual indication of the performance of
      the population of filaments. Direct comparisons show that the data produced by
      automatic tracking is indistinguishable from manual tracking apart from the small
      apparent velocity of non-mobile filaments. The detection process takes about 5
      min and requires little skill or judgement. This can lead to great increases in
      the rate of data analysis in motility work.

PMID- 8884605
TI  - Filament compliance and tension transients in muscle.
AB  - Huxley and Simmons (1971) proposed an explanation for some striking features in
      the transient tension response of a tetanized muscle fibre to sudden stretch or
      release. More recent work has shown that the stiffness of cross-bridges in
      skeletal muscle is an order of magnitude greater than appeared at that time. On
      the simplified treatment used in that paper, this would cause serious
      disagreement with the experimental observations. It is shown here analytically
      and by computer simulations that these discrepancies disappear when account is
      taken of (a) the range of positions of myosin molecules relative to attachment
      sites on the thin filament and (b) the recently-discovered compliance in the thin
      filaments.

PMID- 8884606
TI  - A novel methodology for simultaneous assessment of the effects of 5
      hydroxytryptamine on primary afferent polarisation and synaptic transmission in
      rat dorsal horn neurones in vitro.
AB  - The rat hemisected spinal cord in vitro preparation was used to test
      simultaneously the effects of 5-hydroxytryptamine (5-HT) on primary afferent
      polarisation and synaptic transmission onto dorsal horn (DH) neurons. Primary
      afferent polarisation was measured from the cut end of a transected lumbar dorsal
      root (DR; L3-L6) using tight suction electrodes coupled to a D.C. amplifier.
      Conventional sharp microelectrodes were used to record intracellularly the
      excitatory postsynaptic potential (EPSP) evoked by high intensity electrical
      stimulation (100 microA, 100 microseconds) of another DR contiguous to that used
      for the suction electrode recording. Superfusion of 5-HT (5-10 microM) caused
      primary afferent depolarisations (PAD) of 227.5 +/- 26.5 microV (mean +/- SEM)
      and 221 +/- 32 microV, respectively, values comparable to the PAD caused by 10
      100 microM gamma-aminobutyric acid (GABA) superfusion. 5-HT-induced PAD was
      tetrodotoxin (TTX) resistant and non-additive to capsaicin-induced PAD suggesting
      a direct depolarising action of 5-HT on a population of primary afferents which
      may include a high proportion of unmyelinated fibres. Simultaneous intracellular
      recordings showed that 5-HT, in addition to generating PAD, depressed primary
      afferent-evoked synaptic transmission to DH neurons reflected by a significant
      reduction (p < 0.05) in the amplitude and duration of the EPSP. In contrast,
      GABA, despite producing a PAD of similar amplitude, failed to depress synaptic
      transmission. These data suggest that PAD alone may be insufficient to account
      for the 5-HT-induced depression of synaptic transmission. This novel experimental
      approach offers a means to explore further the possible causal relationship
      between pre- and post-synaptic effects of 5-HT in the DH and its ability to
      modulate somatosensory processing and nociception.

PMID- 8884607
TI  - Solid-phase radioimmunoassay and chemiluminoimmunoassay for somatostatin in
      unextracted rat plasma.
AB  - Measurement of somatostatin (SS) in small microliter volumes of rat plasma
      obtained from the hypophysial portal circulation would be aided by a sensitive
      and robust technique not dependent on extraction. We have developed
      radioimmunoassay (RIA) and chemiluminoimmunoassay (CIA) for SS in unextracted rat
      plasma from a previously described solid-phase method in human plasma. Plasma SS
      was captured by primary antibody bound to second antibody coated polystyrene
      bead. After incubation the bead was washed and [125I]Tyr1-SS added. Following
      overnight incubation and washing, the bead was counted. The sensitivity for 50
      microliters plasma was 11 pg/ml. Parallel displacement with abdominal portal and
      hypophysial portal plasma was demonstrated. For direct CIA, SS was labeled with
      acridinium and purified using 2 sequential gradient elutions on reversed-phase
      HPLC. Labeled SS performed satisfactorily in solution CIA, but did not bind well
      in solid-phase CIA. Hence, an indirect CIA using biotinylated SS and quantitation
      by acridinium labeled streptavidin was established with equivalent performance to
      solid-phase RIA. In summary, we have developed and validated sensitive and robust
      solid-phase RIA and indirect CIA for SS in unextracted rat plasma. This solid
      phase method could serve as a universal system for the measurement of other
      neuropeptides in rat plasma.

PMID- 8884608
TI  - A renumbering method to decrease matrix banding in equations describing branched
      neuron-like structures.
AB  - The solution to matrix equations which describe branched neuron-like structures
      can be made more efficient by minimizing matrix banding. This can be accomplished
      through the reordering of the compartmental numbering system. The renumbering
      method presented here extends upon the numbering method of Hines ((1984) Int. J.
      Biomed. Comput., 15: 69-76). A demonstration of efficient numbering will be
      presented for several general cases of branching structures. Theoretical
      computational savings can be estimated for the above structures. An algorithm to
      renumber a matrix already in Hines form will be described. Branched nerve
      equations, electrical networks and chemical reaction models are examples of
      systems which can benefit from this application.

PMID- 8884609
TI  - Characterization of the technique involved in isolating Schwann cells from adult
      human peripheral nerve.
AB  - Only recently has it been possible to isolate large quantities of adult derived
      Schwann cells (SCs) from peripheral nerves in cell culture. These techniques can
      be easily applied to the isolation of human SCs. We evaluated the influence of
      donor age and length of explant culture time on the purity of the human SC
      preparations obtained from a large number (n = 35) of live organ donors ranging
      in age from 1 to 63 years. The average SC purity from all donors was 92.7 +/-
      2.73% and did not appear to be influenced by donor age or duration of culture
      time in excess of 1 week. Myelin debris was a prominent feature of human SCs
      prepared in culture and could be detected within histological sections of
      cultured peripheral nerve segments as well as within human SCs obtained from
      enzymatic dissociation of the peripheral nerves. This report supports the
      reproducibility of the techniques involved in isolating human SCs from peripheral
      nerve from a large series of donors and addresses the mechanism in which a period
      of cell culture permits the isolation of large quantities of adult human SCs.

PMID- 8884610
TI  - Areal extent quantification of functional representations using intrinsic signal
      optical imaging.
AB  - An important parameter often investigated in the characterization of cortical
      functional organization is the areal extent of functional modules. Because it
      allows the visualization of functional modules with high spatial resolution in a
      noninvasive way to the cortex, intrinsic signal optical imaging (ISI) can be
      employed for the quantification of these areal extents. The present paper
      describes the use of the normalized threshold analysis of areal extent
      quantification for the objective assessment of single-whisker functional
      representations in the primary somatosensory cortex of adult rats. As the success
      of areal extent quantification depends on the ability of ISI to allow
      visualization of cortical representations with minimal stimulus-dependent blood
      vessel representations, which are commonly encountered by ISI, the present paper
      also describes the further development of the intratrial analysis of
      visualization for minimizing these vessel representations. Both analyses are
      discussed with respect to their advantages as well as their inherent limitations.

PMID- 8884611
TI  - Quantitative microdialysis of serotonin and norepinephrine: pharmacological
      influences on in vivo extraction fraction.
AB  - The present study was designed to investigate the potential influence of various
      neuronal processes including uptake, release and metabolism, on the in vivo
      microdialysis extraction fraction (Ed) of serotonin (5HT) and norepinephrine
      (NE). Paroxetine administration decreased the Ed of 5HT in the nucleus accumbens
      from 24 +/- 3 to 18 +/- 0.2% (p < 0.05). Similarly, desipramine infusion reduced
      the NE Ed from 35 +/- 2 to 26 +/- 1% (p < 0.05). However, perfusion with
      pargyline or tetrodotoxin had no effect on the Ed of either 5HT or NE. Perfusion
      with agonists for the 5HT, alpha-adrenergic, D2 and histamine receptors had no
      effect on the Ed of 5HT. In the same manner, perfusion with the alpha-adrenergic
      agonists, methoxamine or clonidine, did not affect the Ed of NE. These data are
      in agreement with experimental results obtained for dopamine in the nucleus
      accumbens and the theory of quantitative microdialysis which predicts that only
      changes in the rate of clearance will change Ed of monoamines. These results
      suggest that, like DA, changes in the Ed for 5HT or NE are indicative of changes
      in the reuptake of these neurotransmitters. The results also indicate that
      pharmacological agents which do not affect uptake have no effect on the
      extraction fraction.

PMID- 8884612
TI  - Biochemical characteristics of a primary blood-brain barrier cell culture system
      as a function of the activity of the proteases used in tissue disaggregation.
AB  - Utilization of primary cultured brain capillary endothelial cells (BCECs) as an
      in vitro model of the blood-brain barrier (BBB) depends on the extent to which
      cultured BCECs retain the in vivo characteristics. Recently, we have reported
      that consistent isolation of BCECs that mimic the in vivo BBB depends on whether
      a specific ratio between the weight of the isolation enzyme (collagenase/dispase)
      and the weight of the capillaries present during the isolation is used. Since it
      is possible for the same weight of an enzyme to possess different activity
      levels, it is felt that activity rather than weight of an enzyme should be used
      in arriving at the above ratio. Therefore, using bovine brain as the source of
      BCECs, we have quantified the amount of collagenase/dispase needed for optimal
      isolation of BCECs and retention of their phenotypic properties in terms of
      collagenase/dispase activity per g of capillaries. Monolayers of bovine BCECs
      isolated at 0.15 or 0.30 units of collagenase and 2.06 or 4.12 units dispase per
      g of capillaries gave the best overall quality as judged by their permeability
      characteristics and the activities of angiotensin converting enzyme, alkaline
      phosphatase and gamma-glutamyl transpeptidase.

PMID- 8884613
TI  - Glutamate release by the intact light-responsive photoreceptor layer of the
      Xenopus retina.
AB  - In order to study glutamate release from light responsive photoreceptors, we used
      an eyecup preparation treated with detergent and distilled water, which permitted
      removal of the inner retina. The remaining 'reduced' retina consists mainly of
      photoreceptors attached to the pigment epithelium. The viability of the
      preparation was established by exclusion of trypan blue, light and electron
      microscopic examination of the photoreceptor layer and by intracellular
      recordings from rods. The 'reduced' retina was superfused at 1 ml/h and overflow
      samples were analyzed for their glutamate content by a fluorimetric enzyme assay.
      We tested the response to dark and light adaptation and to treatment with 100
      microM CdCl2. We found a baseline glutamate level in light-adapted preparation
      which was not affected by cadmium. Dark adaptation induced a 2-fold increase of
      glutamate release, which was completely blocked by cadmium.

PMID- 8884614
TI  - Visualization of autophosphorylation of Ca2+/calmodulin-dependent protein kinase
      II in hippocampal slices.
AB  - We describe a method for visualizing the relative spatial distribution of
      autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) in
      neuronal subcompartments within hippocampal slices. The method employs a
      monoclonal antibody recognizing only autophosphorylated CaMKII, and an affinity
      purified polyclonal rabbit antisera recognizing only nonphosphorylated CaMK II
      (Patton et al. (1993) Mol. Biol. Cell, 4: 159-172). 50 microns sections cut from
      fixed 500 microns hippocampal slices are double-labeled with these antibodies
      bound by secondary antibodies coupled to fluorescein and Cy3, respectively. The
      distribution of the two antigens in identical optical sections is recorded by
      dual channel confocal laser scanning microscopy (CLSM). The digital images are
      analyzed with the program MacPhase to determine the relative levels of staining
      with antibodies to phosphokinase and antibodies to nonphosphokinase in
      subcellular domains of neurons. Comparison of data from paired control and
      experimental slices reveals the spatial distributions of changes in levels of
      autophosphorylated CaMKII produced by pharmacological treatments. We are able to
      detect and spatially resolve differences in levels of autophosphorylation of CaMK
      II between slices subjected to Ca2+ depletion (low autophosphorylation) and
      slices treated with a phosphatase inhibitor (high autophosphorylation).

PMID- 8884615
TI  - Electrically evoked 5-hydroxytryptamine efflux in rat hypothalamus studied using
      in vivo amperometry.
AB  - Changes in 5-hydroxytryptamine (5-HT) efflux have been studied for the first time
      using differential pulse amperometry (DPA). In vitro observations show that the
      oxidation potential of 5-HT at 37 degrees C is 160 mV. The amperometric signal
      corresponding to 5-HT was measured in the lateral hypothalamus after brief
      electrical stimulation of the dorsal raphe nucleus (10 s, 25 or 50 Hz, 300
      microA) every 5 or 10 min. Pargyline (100 mg/kg ip) and d-norfenfluramine (5
      mg/kg ip) increased the signal to 194 and 243%, respectively. Tetrodotoxin (1
      microliter, 100 mM), injected in the proximity of the working electrode, caused
      the signal to disappear. 8-OH-DPAT (250 micrograms/kg sc) reduced it to 64% for
      about 1 h and this effect was completely prevented by the 5HT1A antagonist WAY
      100635 (1 mg/kg sc). L-Tryptophan (100 mg/kg ip) increased the amperometric
      signal to 136%. No change was detected when the 5-HT precursor was given to rats
      pretreated with PCPA (150 mg/kg per day p.o. for 3 days). In conclusion, DPA
      represents a sensitive and selective approach for studying 5
      hydroxytryptaminergic function, offering a good temporal and anatomical
      specificity.

PMID- 8884616
TI  - A combined stereotaxic adaptor and anaesthesia apparatus for microdialysis
      studies in small rodents.
AB  - Intracerebral microdialysis in the bank vole (Clethrionomys glareolus) challenges
      the accuracy and precision of the stereotaxic implantation technique because of
      the small brain size. In this paper, a miniaturized stereotaxic head holder is
      described that allows precise alignment of bone landmarks on the skull and
      prevents all movement after fixation by clamping the skull symmetrically at the
      os parietale and at the os nasale. In addition, the head holder is adapted for
      inhalation anaesthetic delivery in order to ensure stable anaesthetic depth over
      several hours. The system is not restricted to bank voles but can be readily
      applied to other small experimental animals, which could lead to a more
      widespread use of the microdialysis technique in mice.

PMID- 8884617
TI  - Measurement of purine nucleoside concentration in the intact rat retina.
AB  - Adenosine, produced from the decomposition of adenosine triphosphate, is believed
      to provide protective effects during ischemia. On the other hand, adenosine
      metabolites may serve as precursors for oxygen free radical formation. These
      substances have not been previously measured in intact vertebrate retina, where
      adenosine and its metabolites may play a role in the pathogenesis of ischemic
      injury. The small tissue mass of the retina, particularly in rats, renders these
      measurements challenging. Furthermore, accurate measurement of purine nucleosides
      requires immediate cessation of ongoing adenosine metabolism. Concentrations of
      adenosine and its purine nucleoside metabolites inosine, hypoxanthine, and
      xanthine in the retina of ketamine/xylazine-anesthetized rats were measured after
      in situ freezing using high-performance liquid chromatography. The retina was
      removed from the frozen eyes and analyzed. Quantitative measurements were made
      possible through the use of an internal standard. Ischemia was induced by
      ligation of the central retinal artery. Retinal purine nucleoside concentrations
      did not differ between the two eyes of the rat under control conditions, and
      there was no effect of placement of the ligating suture itself compared to
      completely unmanipulated eyes. Use of two different in situ freezing methods
      yielded comparable results. To evaluate the impact of a period of ischemia, one
      retina of each rat was ischemic for 30 min, and the other, non-ischemic. Our
      measurements were associated with a high degree of reproducibility and minimal
      variability, and significant changes in purine nucleoside concentrations were
      detectable in the retina after 30 min of ischemia. Our method may be used to
      assess the role of adenosine and its metabolites in the pathogenesis of ischemic
      neuronal injury, including in the retina.

PMID- 8884618
TI  - Method for single-trial readiness potential identification, based on singular
      spectrum analysis.
AB  - This paper presents a brief description and the advantages of the singular
      spectrum analysis (SSA). SSA has recently been recommended for analysis of short,
      noisy time series. The method was applied to single trials of EEG activity at Cz,
      Fz, C4, Pz and C3, recorded 3.6 s prior to and 1.2 s after the onset of a
      voluntary motor act. This specific activity is known in its averaged form as
      readiness potential (RP) and is considered to reflect the preparation of the
      voluntary movement. However, some physiological investigations require
      identification of the parameters of single-trial RPs-their onset and successive
      phases. SSA is based on analysis of the principal components in vector space of
      delay coordinates of time series. As a result, SSA algorithm decomposes real data
      records to components reflecting the trend, alpha and beta frequency bands,
      respectively, whose oscillations appear or disappear in different time instants.
      The latter were interpreted to distinguish different dynamical stages of the
      movement preparatory process.

PMID- 8884619
TI  - Determination of channel open probabilities from multichannel data.
AB  - We developed a method for determining whether channels in a multichannel patch or
      bilayer have the same or statistically significantly different open
      probabilities. We use a maximum likelihood method to fit the distribution of
      (unbinned) current amplitudes and to provide estimates of individual channel open
      probabilities, single channel currents, and standard deviations of the channel
      currents. These parameters are used to compare models with increasing constraints
      on the open probabilities including the model where all channels have different
      open probabilities and the model where all channels have the same open
      probability. A chi 2 statistic is used to identify models that are statistically
      less likely to predict the data. The ability of multichannel data to determine
      individual open probabilities is limited by two factors: the signal to noise
      ratio of the record and the fact that changes in amplitude distributions caused
      by a 0.2 difference in open probabilities are comparable in magnitude to the
      variations caused by random channel gating. These limitations notwithstanding, we
      demonstrate the utility of our approach by using it to analyze the open
      probabilities of 3 large conductance Ca2(+)-activated K+ channels in an
      artificial lipid bilayer revealing the response of one of those channels to GTP
      gamma S.

PMID- 8884620
TI  - Metabolic activity in antigenically identified neurons: a double labeling method
      for high-resolution 2-deoxyglucose and immunohistochemistry.
AB  - The 2-deoxyglucose (2DG) histochemical method of Sokoloff et al. ((1977) J.
      Neurochem., 28: 897-916) has been widely used to map metabolic activity in the
      brain, but lacks sufficient resolution to view individual neurons. Modifications
      of the original method have achieved cellular resolution with emulsion
      autoradiography and tissue apposed directly to the autoradiogram, but the ability
      to discriminate clearly between populations of neurons identified by antigenic
      markers has been lacking. A method is presented which makes it possible, for the
      first time, to study the metabolic activity of every immunohistochemically
      labeled neuron in a neural system of interest. The procedure combines a high
      resolution 2-deoxyglucose technique and immunostaining for glutamate
      decarboxylase (GAD) or other antigens. The method stabilizes label during
      immunohistochemical processing by the addition of glycogen to all solutions that
      come into contact with tissue after sectioning. The postulated effect of the
      added glycogen is to limit diffusion or net efflux of unfixed macromolecules
      which contain 2-deoxyglucose label. When used with a GAD antibody to label
      putative GABAergic inhibitory interneurons, the procedure allows a direct
      assessment of the extent of inhibition in the circuitry of cerebral cortex. A
      detailed protocol for this double-labeling procedure is presented, along with
      examples of the labeling patterns obtained in the whisker-related barrel field of
      rodent somatosensory cortex.

PMID- 8884621
TI  - Postembedding immunocytochemistry of large sections of brain tissue: an improved
      flat embedding technique.
AB  - A method for osmicating, dehydrating, and flat-embedding large slabs of brain
      tissue in epoxy resin is presented. This permits the production of semithin
      sections for postembedding immunocytochemistry that are far larger than can be
      obtained with other embedding approaches. Vibratomed slabs, 50-200 microns thick
      and as large as 6 x 8 mm are embedded in a 'soft' Araldite epoxy. The slabs are
      laminated onto the flat surface of a pre-cast epoxy slide. After polymerization,
      the tissue can be studied on the slide as a whole mount to view osmicated fiber
      tracts or, in experimental tract tracing studies, to locate retrogradely labeled
      cells before semithin sections are cut. The rigidity of the epoxy slide ensures
      that the slabs remain flat and are easily removed and mounted for resectioning.
      Semithin sections are cut using 6 mm wide glass knives or a 6 mm wide diamond
      knife and are mounted singly or in serial pairs and immunostained using
      conventional etching and immunoperoxidase techniques. The relative softness of
      the epoxy permits dozens of semithin sections to be cut from large blocks without
      appreciably degrading a glass knife edge. After further polymerization the
      embedment is also compatible with electron microscopy.

PMID- 8884622
TI  - The variability of cerebrovascular reactivity with posture and time.
AB  - Transcranial Doppler (TCD) ultrasonography has been used in a variety of clinical
      contexts to assess cerebrovascular reserve by measuring carbon dioxide
      reactivity. Reproducibility with time and altered position of the patient is
      examined in the present study. Carbon dioxide reactivity was determined in 10
      healthy volunteers using TCD. Hypocarbia was produced by voluntary
      hyperventilation, and hypercarbia was produced by rebreathing from a circuit
      primed with 7% carbon dioxide. Each patient was studied in the supine position
      twice (1 week apart) and once in the seated position. Carbon dioxide reactivity
      was determined from linear regression analysis of paired middle cerebral artery
      flow velocity and end-tidal carbon dioxide values. Analysis of covariance for
      repeated measures was used for statistical analysis. Both the absolute slope and
      the relative slope (absolute slope expressed as a percentage of flow velocity at
      40 mm Hg) were compared. In the supine position, flow velocity, absolute and
      relative slopes, and mean arterial pressure were similar from one week to the
      next at all carbon dioxide levels. In contrast, flow velocity, mean arterial
      pressure (adjusted for hydrostatic gradient), and absolute slope were decreased
      in the seated position (p < 0.05). No difference was observed when the relative
      slope was used for comparison. We conclude that absolute carbon dioxide
      reactivity is reproducible over time but may be influenced by position. Relative
      reactivity (relative slope), however, was both time and position independent.

PMID- 8884623
TI  - Effects of perioperative indomethacin on intracranial pressure, cerebral blood
      flow, and cerebral metabolism in patients subjected to craniotomy for cerebral
      tumors.
AB  - This study was carried out to evaluate the effects of perioperative indomethacin
      on intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral
      metabolism. Twenty patients subjected to craniotomy for supratentorial cerebral
      tumors were anesthetized with thiopental, fentanyl, nitrous oxide, and
      isoflurane. A PaCO2 level averaging 4.8 kPa (median) was achieved. The patients
      were randomized to intravenous indomethacin 50 mg or placebo administrated after
      exposure of the dura. ICP was measured continuously subdurally with a 22-gauge
      canula connected to a transducer. CBF and the arteriovenous difference of oxygen
      (AVDO2) were measured twice, before and after indomethacin/placebo
      administration. A significant decrease in ICP from 6.5 to 1.5 mm Hg (median) was
      found after indomethacin administration. This decrease was caused by a
      significant decrease in CBF associated with a significant increase in AVDO2.
      Indomethacin did not affect the cerebral metabolic rate of oxygen, the
      arteriovenous difference of lactate, or the lactate/oxygen index, suggesting that
      indomethacin did not provoke global cerebral ischemia. In the indomethacin group,
      dura was sufficiently relaxed in eight of nine patients and dura was opened
      without the occurrence of cerebral swelling. In one patient, mannitol treatment
      was necessary to prevent dural tightness. In the placebo group, mannitol
      supplemented with hypocapnia was applied in five patients. These findings suggest
      that perioperative treatment with indomethacin is an excellent treatment of
      intracranial hypertension during normocapnic isoflurane anesthesia for
      craniotomy.

PMID- 8884624
TI  - Validation of transcranial near-infrared spectroscopy for evaluation of cerebral
      blood flow autoregulation.
AB  - The aim of the study was to evaluate a new noninvasive transcranial near-infrared
      spectroscopy (TNIRS) technique for determination of the lower limit of cerebral
      blood flow (CBF) autoregulation by comparing this technique with the standard
      cerebral arteriovenous oxygen saturation difference (AVDo2) method. In eight
      healthy volunteers, mean arterial blood pressure was increased by infusion of
      angiotensin and decreased by the combination of lower-body negative pressure and
      labetalol. For each 5-mm Hg change in mean arterial pressure, blood was sampled
      from the bulb of the internal jugular vein and a radial artery, and
      simultaneously, the oxygen saturation of hemoglobin in the brain was measured
      with an INVOS 3100 Cerebral Oximeter (Somanetics). The lower limit of
      autoregulation was then calculated by a computer using (a) AVDo2 and (b) the
      difference between arterial oxygen saturation and the saturation determined with
      the cerebral oximeter (ACDo2). The median lower limit of autoregulation
      determined by the two methods was 73 and 78.5 mm Hg, respectively (p > 0.05). A
      statistically significant correlation between relative CBF (percentage of
      baseline) determined with the two methods was found below the lower limit of
      autoregulation (1/AVDo2 = 12 + 0.8 x 1/ACDo2; r = 0.55; p < 0.001). For all the
      98 pairs of saturations registered, the correlation was 0.37 (p < 0.001), the
      mean difference was 16%, and the limits of agreement were -2.2 and 33.8%. We
      conclude that the cerebral oximeter might be useful in evaluation of the lower
      limit of cerebral autoregulation. This method, however, is of no value for
      estimation of levels of global cerebral oxygen saturation.

PMID- 8884625
TI  - The effect of right internal jugular vein cannulation on intracranial pressure.
AB  - Access to the central venous circulation is often necessary in patients who have
      elevated intracranial pressure. It has been suggested that a disadvantage of the
      internal jugular vein approach to the central circulation may be an elevated
      intracranial pressure. The purpose of this prospective study was to evaluate the
      effect of right internal jugular vein cannulation on intracranial pressure in
      patients who are at risk of intracerebral hypertension. Eleven adult patients
      studied in the intensive care unit were evaluated. The population included those
      patients who were admitted to the neurosurgical intensive care unit requiring
      intracranial pressure monitoring and central venous access. With the intracranial
      pressure monitor in place, patients were put in supine and 30 degrees head-up
      positions while intracranial pressure was recorded. The Queckenstedt maneuver was
      performed on all patients. A central venous line was then placed in the right
      internal jugular vein, and intracranial pressure was recorded. The Queckenstedt
      maneuver was again performed in the study population, and intracranial pressure
      measurements were recorded for the right, left, and bilateral compression of the
      internal jugular vein. The results of the intracranial pressure measurements
      before and after placement of the central venous line were statistically analyzed
      using single-factor analysis of variance over time. The mean Glasgow coma and
      Apache II scores for the study groups were 8 +/- 4 and 15 +/- 6, respectively.
      There were no significant differences in heart rate; cerebral perfusion pressure;
      or systolic, mean, or diastolic pressures throughout the study period. There was
      no statistical difference found between the intracranial pressures at any time
      point throughout the study. Furthermore, no difference was found in percentage
      change from baseline intracranial pressure data throughout the study period. Our
      results suggest that cannulation of the right internal jugular vein is a safe
      approach to the central circulation in patients at risk of intracranial
      hypertension. A description of the possible accommodating mechanisms are
      outlined.

PMID- 8884626
TI  - Percutaneous dilational tracheostomy after anterior cervical spine fixation.
AB  - After spinal cord injury, quadriplegic patients generally require tracheostomy
      for ventilatory support and airway clearance. Early tracheostomy has several
      advantages over translaryngeal intubation, but in patients who undergo anterior
      surgical fixation of the spine, it is often delayed until after recovery of the
      surgical wound. We report the case of a quadriplegic patient who underwent a
      successful percutaneous dilational tracheostomy with the Ciaglia technique after
      surgical fixation of the spine. The percutaneous dilational technique minimizes
      the injury to the adjacent structures of the neck and the risk of stomal
      infection. Therefore, it should be considered the technique of choice when an
      early tracheostomy is indicated for quadriplegic patients who have undergone
      anterior surgical fixation of the cervical spine.

PMID- 8884627
TI  - Comparative effects of propofol, pentobarbital, and isoflurane on cerebral blood
      flow and blood volume.
AB  - While intravenous and volatile anesthetics have widely differing effects on
      cerebral blood flow (CBF), clinical studies suggest that the relative differences
      in their effects on intracranial pressure (ICP) may be smaller. Because acute
      changes in ICP are determined primarily by changes in cerebral blood volume
      (CBV), we compared the impact of propofol, pentobarbital, and isoflurane on CBF
      and CBV in rats. Equipotent doses of the three agents were determined by tail
      clamp studies. Animals were then anesthetized with propofol (20 mg/kg load, 38
      mg.kg-1.h-1 infusion), pentobarbital (30 mg/kg load, 20 mg.kg-1.h-1 infusion), or
      isoflurane 1.6-1.8%. Two hours later, CBF and CBV were measured using 3H-nicotine
      as a CBF tracer, and 14C-dextran and 99mTc-labeled red cells as markers for
      cerebral plasma and red blood cell volumes (CPV and CRBCV), respectively. Total
      CBV was the sum of CPV and CRBCV. CBF was 2.0-2.6 times greater with isoflurane
      than with propofol or pentobarbital (137 vs. 67 and 52 ml.100 g-1.min-1,
      respectively). By contrast, while CBV was greater in the isoflurane group than in
      either the propofol or pentobarbital groups, the magnitude of the intergroup
      differences were much smaller (propofol = 2.49 +/- 0.28 ml/100 g; pentobarbital =
      2.27 +/- 0.15 ml/100 g; isoflurane = 2.77 +/- 0.24 ml/100 g, mean +/- SD). These
      results suggest that the simple measurement of CBF may not adequately describe
      the cerebrovascular effects of an anesthetic, at least with respect to predicting
      the magnitude of the agents likely effects on ICP.

PMID- 8884628
TI  - What workup should we require for a patient who has had one TIA and demonstrates
      80% carotid stenosis?
AB  - The workup that I would recommend of a patient with a single TIA and an 80%
      carotid stenosis would include carotid ultrasound combined with MRA. If these
      studies correlated, then I would proceed with carotid endarterectomy after
      medicine or cardiology consultation and workup for coronary artery disease.

PMID- 8884629
TI  - Symptomatic carotid stenosis: precarotid endarterectomy evaluation.

PMID- 8884630
TI  - The preoperative evaluation for symptomatic carotid endarterectomy: a debated
      issue.

PMID- 8884631
TI  - Natural distribution of oral Actinobacillus actinomycetemcomitans in young men
      with minimal periodontal disease.
AB  - A total of 1005 subgingival and extracrevicular samples from 201 male recruits,
      18-25 yr old, were selectively cultivated for Actinobacillus
      actinomycetemcomitans. The organism was isolated in 55 subjects (27%); 9.5% of
      pooled subgingival plaque samples from first molars, 14% cheek mucosa, 20% dorsum
      of tongue and 20% saliva samples were culture-positive. In order to divide the
      study population into distinct clinical categories, cluster analysis was
      performed, based on previous caries experience, probing pocket depth categories,
      bleeding scores, visible plaque and calculus. Two clusters (n = 86 and n = 92,
      respectively) were identified with no or minimal periodontal disease (mean +/-
      standard deviation % of periodontal probing depth 1-2 mm 78.7 +/- 10.4% and 57.4
      +/- 12.6%, respectively; virtually no periodontal probing/depth in excess of 4
      mm) and a relatively low DMF-S (22 +/- 13). A third cluster (n = 22) had, in
      contrast, a high DMF-S (47.7 +/- 17.2) and a relatively high % of periodontal
      pockets of > or = 5 mm (5.9 +/- 5.2%). Prevalence of A. actinomycetemcomitans in
      this cluster was 41%, while the organism was found in 23% and 27% in the
      minimally diseased populations (p < 0.15). Whereas no heterogeneity of
      associations between subgingival and extracrevicular occurrence of the organism
      could be ascertained in different clusters, the organism was significantly more
      often identified in extracrevicular material, especially dorsum of tongue
      samples, compared with subgingival plaque (McNemar's chi2 = 12.45, p < 0.001).
      Multiple linear regression analysis revealed the number of A.
      actinomycetemcomitans positive samples as well as the % of sites bleeding on
      probing being positively associated with the % of sites with a probing pocket
      depth of > or = 5 mm (R2 = 0.345, p < 0.0001). The present large-scale
      investigation points to the wide distribution of this putative periodontopathogen
      in young individuals with minimal periodontal disease.

PMID- 8884632
TI  - The relationship between gingival crevicular fluid cathepsin B activity and
      periodontal attachment loss in chronic periodontitis patients: a 2-year
      longitudinal study.
AB  - This study aims to determine whether gingival crevicular fluid (GCF) cathepsin B
      levels, total activity (TA) and concentration (EC) predict progressive attachment
      loss (AL). Seventy-five previously untreated patients with moderate periodontitis
      were recruited. GCF was collected from 16 molar and premolar mesiobuccal sites
      and probing attachment level (PAL) and probing depth (PPD) were measured with an
      electronic probe. Gingival, gingival bleeding and plaque indices were then
      scored. Prior to baseline patients were given basic periodontal treatment after
      which the above procedures were repeated. Carefully localized radiographs were
      taken of the test teeth and repeated annually. Patients were seen 3-monthly for 2
      yr and the procedures were repeated. One hundred and twenty-one AL sites, 90
      rapid AL (RAL) and 31 gradual AL (GAL), in 49 patients were detected. Cathepsin B
      levels (TA & EC) at RAL sites were significantly higher (p < 0.0001) than paired
      control sites at the attachment loss time (ALT) and prediction time (PT). Mean
      levels (TA & EC) over the study period at GAL sites were significantly higher (p
      < 0.0001) than paired control sites. Using a critical value (CV) of 7.5 microU/30
      s (TA) and 30 microU/microL (EC) showed a sensitivity of 100% and specificity of
      99.83% (TA) and 100% and 99.75%(EC) at both ALT & PT. Mean cathepsin B levels (TA
      & EC) were significantly higher (p < 0.0001) at RAL and GAL sites than non
      attachment loss (NAL) sites in AL patients in intrapatient comparisons and mean
      patient levels were significantly higher (p < 0.0001) in AL patients than NAL
      patients in interpatient comparisons. These results indicate that GCF cathepsin B
      may serve as a predictor of attachment loss.

PMID- 8884633
TI  - Cytokine-inducing components of periodontopathogenic bacteria.
AB  - Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8 and tumour
      necrosis factor (TNF) are believed to be the major pathological mediators of
      inflammatory diseases ranging from arthritis to the periodontal diseases. The
      stimuli inducing proinflammatory cytokine induction in the former disease is
      unclear but in the periodontal diseases it is obvious that the stimulus is the
      accumulation of bacteria in the subgingival region. As these bacteria do not
      invade the lesional tissues in large numbers, it is believed that their soluble
      components or products interact with host tissues to induce cytokine gene
      transcription. The paradigm is that lipopolysaccharide is the key bacterial
      component inducing pro-inflammatory cytokine gene expression. However, over the
      past decade a growing number of reports on non-oral bacteria have established
      that many other bacterial components, as well as secretory products, have the
      capacity to induce cytokine synthesis. Some of these, such as the protein
      pneumolysin from Streptococcus pneumoniae, are incredibly potent (in this case
      inducing cytokine synthesis at femtomolar concentrations). This review surveys
      the range of bacterial components and products which have been shown to stimulate
      cytokine synthesis with particular emphasis on the hypothesis that these
      components play a role in the pathology of the periodontal diseases.

PMID- 8884634
TI  - Effects of a rhubarb (Rhei rhizoma) solution and its fractions on the formation
      of calcium phosphate precipitates.
AB  - Inhibitory effects of a rhubarb (Rhei rhizoma) solution and its fractions on the
      formation of calcium phosphate precipitates were studied. The rhubarb solution
      inhibited both the amorphous calcium phosphate (ACP) formation and the rate of
      hydroxyapatite (HAP) transformation, and extended the induction time. When the
      solution was fractionated using membrane filters, a filtrate with the molecular
      weight between 3 and 10 kDa (with 2/3 recovery of polyphenols) was found to be
      responsible for both the ACP formation and the extension of the induction time.
      Another filtrate with the molecular weight below 3 kDa (with 1/3 recovery of
      polyphenols) may be responsible for the inhibition of both the ACP formation and
      the rate of HAP transformation, and the extension of the induction time. When the
      extract of rhubarb was fractionated using a Sephadex LH-20 column chromatography,
      fraction IV greatly inhibited the formation of calcium phosphate precipitates,
      while fractions I, II and III slightly inhibited that reaction. Our finding
      suggests that fraction IV may contain useful substance(s) for the prevention of
      oral calcium phosphate precipitation (calculus formation). However, strong
      calcium chelating properties would limit the concentration that could be safely
      employed.

PMID- 8884635
TI  - Effects of T cell adoptive transfer into nude mice on alveolar bone resorption
      induced by endotoxin.
AB  - Using the method of reconstitution of nude mice with T cells, we examined the
      effects of T cell on alveolar bone resorption induced by repeated injections of
      Escherichia coli endotoxin into periodontal tissue. Three mice groups (normal,
      nude and T cell reconstituted nude mice) were used. Endotoxin derived from E coli
      was repeatedly injected into the gingiva of the mice left mandibles every 48 h
      and the mice were killed on the day after the 1st, 4th, 7th, 10th, 13th and 20th
      injections of endotoxin. Alveolar bone resorption was examined
      histopathologically and histomorphometrically. Bone surfaces in contact with the
      osteoclast were defined as the site of active resorption and the ratios of active
      resorption were compared among the 3 mice groups. Consequently, no active
      resorption was found after the first injection of endotoxin in any group. After
      the 4th injection, active resorption was found in normal mice and T cell
      reconstituted nude mice and gradually rose with the increase in the injection
      frequency. In contrast, few osteoclasts were found even after the 10th injection
      in the nude mice. In addition, there were statistically significant differences
      between the normal mice and nude mice after the 4th and 10th injections (p <
      0.05). These findings suggested that T cell influences periodontal bone
      destruction induced by local administration of endotoxin during the early phases.

PMID- 8884636
TI  - Clonality of Porphyromonas gingivalis, Prevotella intermedia and Prevotella
      nigrescens isolated from periodontally diseased and healthy sites.
AB  - Black-pigmented anaerobes have been implicated as major pathogens in the
      aetiology of adult periodontitis but these organisms are also found in healthy
      sites. This study aimed to examine the relationship between genotypes of black
      pigmented anaerobes and disease status of periodontal sites using restriction
      endonuclease analysis (REA) and ribotyping. The main black-pigmented species
      recovered from sites were Porphyromonas gingivalis, Prevotella intermedia and
      Prevotella nigrescens. Each of the 58 subjects investigated harboured distinct
      genotypes of these three species. Most subjects appeared to be colonized by a
      single genotype of P. gingivalis and Pr. intermedia, whereas multiple types of
      Pr. nigrescens colonized many individuals. Plasmids were only found in a few Pr.
      nigrescens strains. No association was found between the disease status of sites
      and any specific or group of genotypes of either species or presence of a
      plasmid. Since the same genotypes of P. gingivalis, Pr. intermedia and Pr.
      nigrescens were found at both diseased and non-diseased sites in a subject, adult
      periodontitis is not explained by the presence of specially virulent clones of
      these organisms. Their role in periodontitis, therefore, is likely to be
      opportunistic.

PMID- 8884637
TI  - The localization of epithelial root sheath cells during cementum formation in rat
      molars.
AB  - The purpose of this study was to investigate the distribution of epithelial cells
      and the fate of the basement membrane along the root surface of rat molars during
      cementogenesis, and to test the hypothesis that the Hertwig's epithelial root
      sheath (HERS) cells remain on the root surface if mineralization is inhibited. To
      demonstrate the HERS cells and basement membrane, immunohistochemistry with
      antibodies against keratin and laminin were used. The dentin matrix
      mineralization was inhibited by a single injection of 1-hydroxyethylidene-1, 1
      bisphosphonate (HEBP). A modified Gomori staining method was used to monitor the
      inhibition of mineral formation in dentin and cementum. Paraffin sections were
      stained with haematoxylin-eosin, and freeze-dried sections were used for Gomori
      and immunohistochemical stainings. We found that the formation of acellular
      cementum was suppressed above the dentin with inhibited mineralization. Instead,
      a hyperplastic matrix, different from acellular cementum, covered the dentin.
      This hyperplastic cementum had keratin- and laminin-positive cells incorporated;
      such cells were never incorporated in normal acellular cementum. The later
      formation of cellular cementum correlated, in controls, with the disappearance of
      HERS cells from the root surface. Treatment with HEBP resulted in a persistent
      presence of epithelial cells, interpreted as an inhibition of their
      disappearance. In conclusion, there is evidence that the cells of HERS are
      involved in the development of both acellular and cellular cementum. The
      developmental processes of these tissues appear in some way to be influenced by
      or associated with the initial mineralization of the dentin.

PMID- 8884638
TI  - Quadratic calibration curves for the Periotron 6000.

PMID- 8884639
TI  - Smear removal and collagen exposure after non-surgical root planing followed by
      etching with an EDTA gel preparation.
AB  - Low pH aqueous solutions of citric acid have been used in surgical periodontal
      therapy mainly for two reasons. It dissolves smear after a relatively short
      exposure time and it has been claimed to selectively remove root surface
      associated mineral exposing collagen to varying degrees. The use of low pH
      etching agents has recently been challenged in both experimental in vitro and in
      vivo studies based on their necrotizing effect on the surrounding periodontal
      tissues. The purpose of the present study was to assess the efficacy of
      subgingival application of an EDTA gel preparation in removing smear and exposing
      collagen fibers in root surfaces following non-surgical periodontal therapy. Root
      surfaces which were root planed did not reveal any patent dentinal tubuli or
      collagen fibers. This was in contrast to the findings seen after root planing
      followed by etching, where intertubular surfaces were covered by a dense
      fibrillar network extending into patent dentinal tubuli. In high magnification
      these intertubular fibers displayed the cross-striated texture typical for
      collagen fibers. Etching of root planed surfaces with EDTA may thus enhance the
      effect of non-surgical root debridement in the same way as has been shown during
      experimental surgical procedures.

PMID- 8884641
TI  - Comparing measures of reliability for indices of gingivitis and plaque.
AB  - The purpose of this methodological study was to compare methods used to assess
      reliability for gingival inflammation and plaque. Duplicate examinations were
      conducted by one examiner on 17 subjects (506 scoring sites), using the gingival
      index (GI), bleeding points index (BPI), and plaque index (PI). The percentage of
      agreement, the weighted and unweighted kappa coefficients, and Pearson
      correlation coefficients were calculated as statistics of reliability for mesial
      buccal site scores and whole mouth mean scores when appropriate. For mesial
      buccal sites the respective values of the GI, BPI, and PI for weighted kappas
      were: 0.47, 0.49, and 0.75; for the correlation coefficients: 0.47, 0.49, and
      0.76; for unweighted kappas, 0.39, 0.49, and 0.39; and for percentage of
      agreement 66.2%, 76.1%, and 51.2%. For whole mouth means the correlation
      coefficients for the GI, BPI, and PI were 0.87, 0.59, and 0.87, respectively. In
      conclusion, the most useful statistics in assessing the intraexaminer reliability
      of a solo examiner in descending order were the weighted kappa coefficient,
      Pearson correlation coefficient, the unweighted kappa coefficient, and percentage
      of agreement.

PMID- 8884640
TI  - Histochemical and immunocytochemical localization of dipeptidyl peptidases II and
      IV in human gingiva.
AB  - Dipeptidyl peptidase (DPP) II and IV activities were demonstrated in unfixed
      cryostat sections of gingival tissue from chronic periodontitis patients using
      histochemistry with 2-methoxy-4-naphthylamine (MNA) substrates. In the case of
      DPP IV, enzyme localization was confirmed by immunocytochemistry with mouse
      monoclonal antihuman DPP IV (CD26) antibody. Inflammatory cells containing enzyme
      were identified in adjacent sections with mouse monoclonal antibodies directed
      against leukocyte differentiation antigens. Lys-Ala-MNA and Ala-Pro-MNA staining
      in acid buffer for DPP II was only found in a few fibroblasts in superficial
      tissue. Staining with Gly-Pro-MNA and Ala-Pro-MNA in alkaline buffer for DPP IV
      was localized in some CD4 and CD8 positive T lymphocytes, CD68 positive
      macrophages, and fibroblasts and these cells also reacted with the enzyme
      antibody. DPP IV-containing macrophages and T lymphocytes were seen in the
      epithelium. In deeper granulomatous tissue Gram positive and negative bacteria
      stained with the histochemical substrates, but not the DPP IV antibody.
      Fibroblast DPP II and IV might participate in cellular interactions with
      collagen, while T lymphocyte DPP IV may be involved in cell signalling.

PMID- 8884642
TI  - Comparison of 3 periodontal local antibiotic therapies in persistent periodontal
      pockets.
AB  - The aim of this study was to evaluate the efficacy of 3 commercially available
      periodontal systems for local delivery of antibiotics as adjuncts to scaling and
      root planing in treatment of sites with persistent periodontal lesions following
      a course of scaling and root planing. Fifty-four patients with 4 pockets > or = 5
      mm and bleeding on probing and/or suppuration were randomized in 4 treatment
      groups including: scaling and root planing plus application of 25% tetracycline
      fiber (S + Tet) (13 patients), scaling and root planing plus application of 2%
      minocycline gel (S + Min) (14 patients), scaling and root planing plus
      application of 25% metronidazole gel (S + Met) (14 patients), and scaling and
      root planing alone (S) (13 patients). Clinical measurements were taken at
      baseline and 6 weeks after the end of treatment periods. All treatments were
      applied using the distributors' recommended protocols and resulted in significant
      improvement in probing depth, attachment level, bleeding on probing and the
      modified gingival index (MGI) scores. The improvements in clinical parameters
      were greater in all three adjunctive treatment groups than scaling and root
      planing alone. The mean probing depth reductions were: S + Tet = 1.35 mm, S + Met
      = 0.95 mm, S + Min = 0.87 mm and S = 0.60 mm. The probing depth reduction was
      significantly greater in the scaling plus tetracycline fiber group than the
      scaling and root planing alone group (P = 0.002). The difference between groups
      in improvement of attachment level or bleeding on probing was not significant
      Scaling plus tetracycline fiber treatment resulted in the greatest reduction in
      the MGI scores which was significantly greater than all other groups. While the
      frequency of sites with suppuration was markedly reduced following all
      treatments, it reached zero in the scaling plus tetracycline fiber group. No
      serious adverse effects were observed or reported for any treatment. While all
      three locally applied antimicrobial systems seem to offer some benefit over
      scaling and root planing alone, a treatment regimen of scaling and root planing
      plus tetracycline fiber replacement gave the greatest advantage in the treatment
      of persistent periodontal lesions at least during the 6-week period following
      treatment.

PMID- 8884643
TI  - The effect of subgingival antimicrobial therapy on the levels of stromelysin and
      tissue inhibitor of metalloproteinases in gingival crevicular fluid.
AB  - Recent investigations imply that a key mechanism in the pathogenesis of
      periodontal disease may be the ability of oral microorganisms to induce
      production and/or activation of matrix metalloproteinases (MMPs) in the host
      tissues. It has been suggested that the pharmacologic inhibition of MMP activity
      could play an important role in achieving a desirable outcome in periodontal
      therapy. The efficacy of locally delivered antibiotics on the level of gingival
      crevicular fluid (GCF) stromelysin (SL) and tissue inhibitor of
      metalloproteinases (TIMP) on sites with a history of a poor response to
      mechanical treatment was studied. Fifty-two patients with 4 periodontal pockets >
      or = 5 mm and bleeding on probing were randomized into four groups of 13
      patients. One group received scaling and root planing alone and the other three
      groups received scaling and root planing plus a locally delivered antimicrobial
      system. These included 25% tetracycline fiber, 2% minocycline gel, and 25%
      metronidazole gel. The GCF samples taken at baseline and 6 weeks after treatments
      were analyzed using an enzyme linked immunosorbent assay (ELISA). GCF SL levels
      significantly decreased after adjunctive tetracycline fiber (paired t-test, P =
      0.020) and minocycline gel (paired t-test, P = 0.023) treatments whereas it
      remained almost unchanged in the other two groups. While the GCF TIMP level did
      not change significantly in the scaling and root planing alone group, it
      significantly increased for all three adjunctive antimicrobial treatments (for
      tetracycline fiber P < 0.001, minocycline gel P = 0.005, metronidazole gel P <
      0.001). The use of adjunctive locally delivered antimicrobial systems,
      particularly the tetracycline family, may offer an advantage in changing the
      metalloproteinase profile of the GCF to one more compatible with periodontal
      health.

PMID- 8884644
TI  - Gingival fibroblast cytokine profiles in Actinobacillus actinomycetemcomitans
      associated periodontitis.
AB  - Within the in vivo environment human gingival fibroblasts (HGF) may be challenged
      with bacteria or bacterial products. This interaction may result in the release
      of cytokines which are directly or indirectly involved in connective tissue and
      bone catabolism, such as interleukin (IL)-1 beta, IL-6, and IL-8. Our
      investigation has tested the hypothesis that HGF from Actinobacillus
      actinomycetemcomitans (Aa)-infected patients with rapidly destructive forms of
      periodontitis, such as localized juvenile periodontitis (LJP), respond to Aa
      challenge with an exaggerated secretion of IL-1 beta, IL-6, and IL-8. We have
      compared the in vitro profiles of these cytokines by Aa-challenged HGF obtained
      from 2 healthy subjects, 2 Aa-infected, slowly progressing adult periodontitis
      (AP) patients and 2 LJP patients. HGF were challenged throughout a 48-hour period
      with formalinized whole bacterial cells, and culture supernatants were analyzed
      for cytokine content using RIA. No differences were noted in the IL-1 beta
      secretion levels among the different HGF cultures. Although basal (unchallenged)
      IL-6 and IL-8 production was similar in all HGF cultures, HGF from the two LJP
      patients responded to Aa challenge with a more rapid IL-6 and a more pronounced
      IL-8 secretion than healthy or AP HGF. We also tested the ability of human serum
      antibodies against Aa to moderate the Aa-elicited HGF cytokine secretion by
      adding human serum, with normal or elevated antibody content. Both sera appeared
      to have an upregulating effect on IL-6 and IL-8 secretion. Depletion of 95% of
      the anti-Aa antibody from serum by absorption did not affect its activity. Based
      on the response of HGF from two LJP patients, we propose that Aa-induced
      pathology in LJP may be modulated by stimulation of rapid and/or exaggerated
      secretion of cytokines with potential catabolic effects, although studies with a
      larger group of LJP patients are needed to further test this hypothesis.
      Furthermore, serum antibodies against this microorganism do not appear to have a
      neutralizing effect in cytokine-eliciting HGF-Aa interactions.

PMID- 8884645
TI  - Treatment of periodontal disease based on microbiological diagnosis. A 5-year
      follow-up on individual patterns.
AB  - Sixteen patients with advanced periodontitis (more than 3 sites with a probing
      depth > or = 6 mm) were treated with the aim of eliminating Actinobacillus
      actinomyce-temcomitans and Porphyromonas gingivalis and reducing Prevotella
      intermedia below 5% of the total viable count. The patients were followed
      clinically and microbiologically for over 5 years and showed a highly individual
      pattern with respect to presence of indicator bacteria, type of treatment needed
      to accomplish treatment goals, clinical response, and bacterial and disease
      recurrencies. The results of this study suggest that presence of the indicator
      bacteria in microbial samples taken after treatment may identify patients at risk
      for recurrent periodontitis.

PMID- 8884646
TI  - HLA Class II genotypes associated with early-onset periodontitis: DQB1 molecule
      primarily confers susceptibility to the disease.
AB  - DNA typing was performed on 24 Japanese patients with early-onset periodontitis
      (EOP) using the PCR-RFLP method to investigate an association of the
      susceptibility to EOP with the particular HLA class II alleles (HLA-DRB1, -DQA1,
      and -DQB1). DRB1*1401, DRB1*1501, DQB1*0503, and DQB1*0602 were found more
      frequently ("susceptible") in the EOP patients than in healthy controls. In
      contrast, DRB1*0405 and DQB1*0401 were found less frequently ("resistant") in EOP
      patients. All patients carrying DQB1*0602 had an atypical BamHI site in the
      intron upstream of the third exon of the DQB1 gene, which in our previous studies
      appeared to be a susceptible marker for EOP. A comparative analysis of the amino
      acid sequences of these susceptible and resistant HLA-DRB1 and DQB1 alleles
      elucidated some differences in antigen-derived peptide binding sites related to
      the susceptible or resistant alleles. Especially, DQB1*0503 and DQB1*0602 alleles
      carrying aspartic acid at position 57 and glycine at position 70 are increased
      significantly in EOP. Since amino acid residues at positions 57 and 70 on the
      DQB1 molecule are supposed to be involved in antigen binding, amino acid
      substitutions at these positions may affect the immune responsiveness to the
      periodontopathic antigen. Our results suggest that the DQB1 molecule plays a
      crucial role in the pathogenesis of EOP and that the susceptibility to EOP may be
      determined by the binding ability between the peptide and HLA-DQ antigens.

PMID- 8884647
TI  - Validation of quantitative digital subtraction radiography using the
      electronically guided alignment device/impression technique.
AB  - The electronically guided alignment device (EGAD) has been demonstrated to
      function well with a custom fabricated stent for taking radiographs for
      subtraction. The objective of this study is to demonstrate that this device
      functions well when used with an impression bite-block rather than a full arch
      acrylic stent. Nineteen subjects participated. Two vinyl siloxane impressions
      were made for each subject and a pair of x-rays was taken with each impression.
      The location for study was divided among 7 for the maxillary premolar-1st molar
      region, 6 for the mandibular premolar-1st molar region, and 6 for the incisor
      canine region. To simulate bone change 3 bone chips (approximately 1, 7, and 10
      mg) were positioned in the mucobuccal fold when one of each pair of x-rays was
      taken. Pairs of radiographs were subtracted and the bone change (chips) isolated
      by thresholding to determine their area. An aluminum ramp was used to determine
      volume. A strong linear relationship between actual chip weight and equivalent
      aluminum volume (r2 = 0.64, P < 0.001) was obtained for all regions of the mouth
      when considered together. The strongest relationship of the 3 regions was for
      mandibular premolar-1st molar sites, r2 = 0.78. These data indicate that the
      EGAD/impression technique is suitable for taking radiographs in all areas of the
      mouth for quantitative digital subtraction.

PMID- 8884648
TI  - Efficacy of a sonic toothbrush on inflammation and probing depth in adult
      periodontitis.
AB  - This single-blind, 8-week study compared the efficacy of a sonic toothbrush and a
      manual brush in 40 patients with adult periodontitis. Qualitative clinical
      indices and quantitative laboratory methods were used to monitor the periodontal
      status of 3 pockets 5 to 7 mm deep in each subject. Patients were randomly
      assigned either a sonic or manual toothbrush. The two groups were comparable with
      respect to age, gender, and anatomical location of the test sites. Data were
      collected from all sites at baseline and at 2, 4, and 8 weeks. Over the 8-week
      period, both groups showed significant improvements in the clinical indices used.
      Descriptive statistics indicated the sonic brush group had greater improvement
      than the manual group in the clinical parameters (gingival index, bleeding index,
      probing depth, and clinical attachment level). Gingival crevicular fluid (GCF)
      flow was significantly lower in the sonic brush group (P = 0.018). Considerable
      variation was present in the levels detected for both inflammatory cytokines
      tested, however, concentration of interleukin-1 beta was significantly lower in
      the GCF of sonic group patients (P = 0.05), while concentration of interleukin-6
      was significantly reduced in both groups (P < or = 0.05) (t tests). Under these
      conditions, there is some evidence to suggest that the sonic toothbrush is more
      beneficial in resolving inflammation in patients with moderate periodontal
      disease.

PMID- 8884649
TI  - Immunomodulatory and superantigen activities of bacteria associated with adult
      periodontitis.
AB  - Immune dysfunctions are frequently associated with chronic inflammatory diseases.
      Several investigators have reported that patients with severe periodontitis show
      reduced or negligible levels of proliferative responses of peripheral blood and
      gingival lymphocytes to periodontopathic organisms. The purpose of this study was
      to evaluate the influences of products from Porphyromonas gingivalis (P.
      gingivalis) and Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans)
      on lymphocytes obtained from periodontally diseased and non-diseased individuals
      in order to extend our understanding of the possible role of such bacterial
      components as immune modulators. Pooled cultures of either P. gingivalis or A.
      actinomycetemcomitans were disrupted using glass beads in a bead mill to prepare
      whole cell homogenates. These homogenates were then co-cultured with human
      peripheral blood mononuclear cells (PBMC) and known lymphocyte stimulators.
      Cultures were pulsed with tritiated thymidine, harvested, and radio label
      incorporation was determined. Responses to toxic shock syndrome toxin-1 (TSST-1)
      and pokeweed mitogen (PWM) were inhibited at high concentrations of bacterial
      homogenate. However, as the concentration was reduced, responses induced by PWM
      were restored while TSST-1 induced responses remained inhibited. Such results
      suggest that P. gingivalis and A. actinomycetemcomitans contain potent
      immunosuppressants with differential influences on lymphocyte population. These
      effects on B- and T-cells are independent of periodontal disease status and
      appear to exert their influence through non-toxic mechanisms. In addition, work
      currently underway presently indicates that obligate oral anaerobic bacteria such
      as P. gingivalis produce substances with some of the characteristics of
      superantigens.

PMID- 8884650
TI  - Ability of commercial demineralized freeze-dried bone allograft to induce new
      bone formation.
AB  - Demineralized freeze-dried bone allograft (DFDBA) has been used extensively in
      periodontal therapy. The rationale for use of DFDBA includes the fact that
      proteins capable of inducing new bone; i.e., bone morphogenetic proteins, can be
      isolated from bone grafts. Commercial bone banks have provided DFDBA to the
      dental practitioner for many years; however, these organizations have not
      verified the osteoinductive capacity of their DFDBA preparations. The aim of this
      study was to determine the ability of commercial DFDBA preparations to induce new
      bone formation. DFDBA with particle sizes ranging from 200 to 500 microns was
      received from six bone banks using various bone production methods. Different
      lots of DFDBA from the same tissue bank were sometimes available. A total of 14
      lots were examined. The surface area of bone particles in each sample was
      measured morphometrically and the pH of a solution containing the particles after
      suspension in distilled water determined. Samples from each DFDBA lot were
      implanted intramuscularly (10 mg) or subcutaneously (20 mg) into three different
      animals and tissue biopsies harvested after 4 weeks. One sample from each tissue
      bank was implanted and harvested after 8 weeks. At harvest, each area where DFDBA
      had been implanted was excised and examined by light microscopy. The ability of
      DFDBA to produce new bone was evaluated and the amount of residual bone particles
      measured. The results show that bone particles from all tissue banks had a
      variety of shapes and sizes, both before implantation and after 1 or 2 months of
      implantation. The pH of particle suspensions also varied between batches, as well
      as between tissue banks. None of the DFDBA induced new bone formation when
      implanted subcutaneously. Intramuscular implants from three banks induced new
      bone formation after 1 and 2 months. DFDBA from two banks caused new bone
      formation only after 2 months. However, DFDBA from one bank did not induce new
      bone at all. Particle size before implantation correlated with particle size
      after implantation. However, particle size did not correlate with ability to
      induce bone. The results show that commercial DFDBA differs in both size and
      ability to induce new bone formation, but that the two are not related. The study
      also indicates that wide variation in commercial bone bank preparations of DFDBA
      exist and that ability to induce new bone formation also varies widely.
      Furthermore, the results suggest that methods or assays for evaluating the
      ability of DFDBA to induce new bone should be developed and standardized.

PMID- 8884651
TI  - Evaluation of bioabsorbable elastin-fibrin matrix as a barrier in surgical
      periodontal treatment.
AB  - The purpose of this investigation was to test clinically the efficiency of a
      recently described bioabsorbable matrix as a guided tissue regeneration membrane.
      This matrix was prepared from an original reaction between elastin and fibrin
      monomers and is now extensively used in several domains of surgery. The study
      group was composed of 26 patients, with a total of 35 lesions (22 intrabony
      defects, 8 Class II furcations and 5 Class III furcations) presenting moderate to
      advanced adult periodontitis. After initial therapy, measurements were made with
      a calibrated periodontal probe. Probing depth (PD) and gingival margin location
      (GM) measurements were taken twice: immediately before surgery and after 6 months
      before re-entry. Clinical attachment level (CAL), vertical osseous level (VOL)
      and alveolar crest location (AC) measurements were taken during surgery and after
      6 months with re-entry procedures for all the patients. Color change of the
      gingival margin was only observed in 4 defects and device exposure occurred in
      the proportion of 2 out of the 35 defects. No foreign body reaction was observed
      in any case. At the intrabony defects mean PD reduction was 5 mm (P < 0.001), and
      mean gain of CAL was 4 mm (P < 0.001). Mean VOL was 4.3 mm (P < 0.001), mean
      gingival recession was 0.9 mm (P < 0.05) and mean AC was 0.2 mm (NS). At the
      Class II furcation defects the mean PD reduction was 4.5 mm (P < 0.001), mean
      gain CAL vertical was 3.2 mm and CAL horizontal was 4.5 mm (P < 0.001). Gingival
      recession averaged 1 mm (NS). A complete closure was observed in 2 out of the 8
      defects. At the Class III furcation defects the mean PD reduction was 3.6 mm (P <
      0.05) and mean CAL-V gain was 1.5 mm (P < 0.02). However the 5 sites showed no
      horizontal attachment gain and none were unchanged. A very low gingival
      recession, gingival reaction, crestal bone loss, and device exposure occurred
      during this study. This preliminary study suggests that the use of a biosynthetic
      barrier may have beneficial effects in the treatment of intrabony defects and
      Class II furcation defects. Randomized controlled trials are necessary to
      evaluate the efficacy and safety of this bioabsorbable membrane in periodontal
      therapy.

PMID- 8884653
TI  - Is there a role for DFDBA in periodontal regenerative therapy?

PMID- 8884652
TI  - Position paper: epidemiology of periodontal diseases. American Academy of
      Periodontology.
AB  - This paper was prepared by the research, Science, and Therapy Committee of The
      American Academy of Periodontology and is intended for the information of the
      dental profession. It represents the position of the Academy in regard to the
      current state of knowledge about the epidemiology of periodontal diseases. Some
      reference is made to topics that are presented in Tobacco. Use and the
      Periodontal Patient and Periodontal Considerations in the HIV-Positive Patient,
      though this paper takes an epidemiological perspective rather than one
      emphasizing patient care.

PMID- 8884654
TI  - Subtraction radiography.

PMID- 8884655
TI  - Platelet I1-imidazoline binding sites are elevated in depression but not
      generalized anxiety disorder.
AB  - Depressed patients have been reported to have a higher than normal density of
      platelet binding sites for 3H-clonidine, an alpha 2-adrenoceptor agonist.
      Paradoxically, other studies using 3H-alpha 2, antagonists have found no
      differences from controls. Because 3H-clonidine interacts with platelet alpha 2
      adrenoceptors to form G-protein complexes, whereas 3H-alpha 2-antagonists bind
      with uncoupled receptors, an elevation in G-protein coupling might explain this
      paradox. Another possibility is that depression might be associated with
      increased non-adrenergic I1-imidazoline binding sites, which are also clonidine
      sensitive. To distinguish these possibilities, we utilized p125I-clonidine to
      measure density (Bmax) and affinity (KD) of platelet G-protein coupled alpha 2
      adrenoceptors as well as platelet I1 binding sites, and compared diagnostic
      groups of major depressive disorder (MDD), generalized anxiety disorder (GAD) and
      healthy subjects. Specific inhibition of binding by norepinephrine (NE = 10
      microM) was used to selectively quantify alpha 2-adrenoceptors, whereas
      inhibition by 10 microM moxonidine (a > 100-fold selective I1 ligand) quantified
      I1 binding sites under a NE mask. I1 sites were found to be markedly elevated by,
      on average, +136% in MDD patients (p = .0007), whereas there was only a marginal
      increase in alpha 2-adrenoceptor Bmax values in MDD patients (p = .08; GAD and
      healthy subjects did not differ). Treatment of MDD patients for 6-8 weeks with
      desipramine downregulated I1 sites as well as alpha 2-adrenoceptors. Positive
      correlations were also noted for both sites: (a) between Bmax values and the
      severity of depression (using the Hamilton Depression Rating Scale); and (b)
      between end-of-treatment plasma desipramine concentrations and the extent of
      downregulation in Bmax values when subject groups were pooled. None of the
      binding parameters was associated with plasma catecholamine concentrations. The
      results suggest that an increased density of platelet I1 binding sites may
      partially explain the utility of radiolabeled clonidine as a potential biological
      marker for depressive illness, although an additional increase in G-protein
      coupling cannot be excluded.

PMID- 8884656
TI  - Platelet I1-imidazoline binding sites are decreased by two dissimilar
      antidepressant agents in depressed patients.
AB  - Previous studies have indicated that there may be a dysregulation of alpha 2
      adrenoceptors and imidazoline receptors in depression. This study compares the
      effects of chronic antidepressant treatment with a serotonin reuptake inhibitor
      (fluoxetine) versus a noradrenaline reuptake inhibitor (desipramine) on the
      binding parameters of the platelet imidazoline binding site (subtype I1) and of
      the platelet alpha 2-adrenoceptor in depressed patients. After 6 weeks of
      treatment with either antidepressant, platelet I1 binding sites became normalized
      (i.e. downregulated). A negative correlation was obtained between plasma
      epinephrine concentrations and platelet alpha 2-adrenoceptor Bmax values within
      the samples, but no correlation was obtained between any plasma catecholamine and
      a platelet I1 binding parameter. An additional finding was the increased affinity
      of alpha 2-adrenoceptors for p125I-clonidine in untreated depressed patients
      compared to healthy subjects. Because of the density of platelet I1 binding sites
      was downregulated by both of the antidepressants, we postulate that a decrease in
      platelet I1 binding site density may be related to an improved state from
      depression that these antidepressants produce.

PMID- 8884657
TI  - Data analytic techniques for treatment outcome studies with pretest/posttest
      measurements: an extensive primer.
AB  - This paper discusses several data analytic technique, for examining treatment
      efficacy in pretest-posttest control group designs. The following approaches are
      described: ANOVA on post scores, ANOVA on difference scores, split-plot repeated
      measures ANOVA, profile analysis, and ANOCOVA with prescore as the co-variate.
      Guidelines for choosing between available techniques are provided; the primary
      focus here is on the nature of the null hypothesis, the assumptions underlying
      the approach, and the power of the procedure. The importance of examining the
      characteristics of the data set in selecting an analytic technique is
      illustrated.

PMID- 8884658
TI  - Monoamine precursors, transmitters and metabolites in cerebrospinal fluid: a
      prospective study in healthy male subjects.
AB  - In order to elucidate methodological aspects of CSF investigations, 14 healthy
      male subjects were lumbar-punctured at the L4-5 level following a standardised
      procedure. CSF concentrations of precursors, transmitters and transmitter
      metabolites were used as dependent variables, while age, height, body weight,
      atmospheric pressure and some other factors served as independent variables. 5
      HIAA and HVA (but not HMPG) have pronounced concentration gradients. We also
      found CSF gradients for the precursors tryptophan and tyrosine, as well as for
      serotonin, dopamine and the dopamine metabolite DOPAC. Dopamine and atmospheric
      pressure showed a positive intercorrelation. Age correlated curvilinearly (convex
      upward) with tryptophan but showed a negatively directed linear correlation with
      serotonin. Serotonin and 5-HIAA showed no intercorrelation. Our results suggest
      an age-dependent disposition of tryptophan in the CSF. The absence of a
      correlation between serotonin and 5-HIAA might be inconsistent with the notion
      that 5-HIAA is a marker of central serotonin turnover. The comparatively high
      body weight of our volunteers might explain the lack of a gradient for HMPG.

PMID- 8884659
TI  - 5-Hydroxy-indolacetic-acid (5-HIAA) serum levels in depressive patients and ECT.
AB  - In 31 drug and ECT naive melancholic patients, serum levels of the major
      metabolite of serotonin 5-hydroxy-indolacetic-acid (5-HIAA) were estimated in the
      first and third ECT of a course. Plasma samples were taken before ECT and 1, 60
      and 120 min thereafter. The estimations were done by a new high performance
      liquid chromatography method (HPLC). After the seizure, a statistically
      significant decrease of 5-HIAA serum levels was observed over both ECTs. There
      was a significant increase in 5-HIAA serum levels from the first to the third
      ECT. ECT was found to influence serotonin turnover. It might be interpreted that
      ECT improves serotonergic responsiveness and neurotransmission. There was no
      significant correlation between 5-HIAA levels and gender, or age of the patients,
      or seizure duration. Furthermore, the severity of depression and treatment
      response did not correlate with certain 5-HIAA serum level patterns.

PMID- 8884660
TI  - The PHA-induced calcium signal in lymphocytes is altered after blockade of K(+)
      channels in Alzheimer's disease.
AB  - Several lines of evidence indicate that alterations in intracellular calcium
      homeostasis with sustained elevation of free calcium ions ([Ca2+]i) might be
      important in the pathophysiology of Alzheimer's disease (AD). Recent studies with
      peripheral blood-cells have demonstrated that investigation of regulatory
      mechanisms in calcium homeostasis might be more promising than determining only
      resting or stimulated [Ca2+]i values. With respect to the importance of potassium
      (K+)-channels in intracellular calcium regulation we have investigated whether a
      potassium channel dysfunction, already demonstrated for AD fibroblasts
      (Etcheberrigaray et al., 1993, Proceedings of National Academy of Sciences USA,
      90, 8209-8213), could be observed in circulating lymphocytes as well. Thus, we
      studied the influence of the K(+)-channel inhibitor tetraethylammonium (TEA) on
      basal and PHA-stimulated [Ca2+]i in lymphocytes from AD (n = 20), non-demented
      depressed patients (n = 15) and age-related healthy controls (n = 23).
      Preincubation of lymphocytes with 100 mmol/l TEA resulted in a 45.5 +/- 8.8%
      inhibition (mean +/- SD) of the PHA induced rise in [Ca2+]i in healthy controls
      and 37.3 +/- 11.3% inhibition in depressed patients. With lymphocytes of AD
      patients, this effect of TEA was significantly reduced (23.2 +/- 8.8%, p < .001).
      If the individual data are considered there was almost no overlap between AD
      patients and healthy controls, since only three (15%) AD patients responded to
      TEA with > 30% inhibition, but only one of the controls (5%) responded with < 30%
      inhibition. Besides the reduced signal-inhibition by blockade of K(+)-channels we
      have observed a delayed response of AD lymphocytes in [Ca2+]i rise after PHA
      stimulation, suggesting that functional plasticity of the cells is reduced.
      Although the significance and molecular basis of this K(+)-channel dysfunction
      are not yet determined, the presented data are of great significance because of
      diagnostic reasons and especially because this model thus offers a possibility to
      investigate functional cellular alterations in vivo.

PMID- 8884661
TI  - Effects of sex steroids on protein synthesis in cultured human lymphocytes.
AB  - In cultured human lymphocytes, oestrogen and progesterone at concentrations found
      in plasma during the normal menstrual cycle, significantly increase the
      incorporation of [35S] methionine into protein and, in addition, both hormones
      significantly alter the relative synthesis of certain proteins. At concentrations
      found in plasma during pregnancy, some changes are augmented while others are
      reversed. These specific sex-steroid-induced changes in protein synthesis provide
      possible peripheral biological markers of hormone action which may be tested for
      their association with predisposition to, and/or onset of, conditions such as
      postpartum psychiatric illness.

PMID- 8884662
TI  - Community reactions to reproductive health care at three school-based clinics in
      Louisiana.
AB  - Despite the growing success of school-based health care during the past two
      decades, the issue of providing reproductive health care at school-based health
      centers remains controversial. In this article, focus group data from three
      school-based centers in Louisiana, each in different stages of development,
      demonstrates how the controversies about reproductive health may frame more
      general concerns about school-based care. In addition, community readiness to
      address directly problematic sexual behavior relates not only to the specific
      needs and priorities of the community but to recognition of the negative effect
      of the consequences of sexual behavior such as pregnancy, high drop out, and
      absenteeism rates on a community's educational, rather than social, goals and
      values.

PMID- 8884663
TI  - The Ready-to-Learn program: a school-based model of nurse practitioner
      participation in evaluating school failure.
AB  - The Ready-to-Learn program, a school-based initiative begun in 1994 in three
      inner-city elementary schools in Hartford, Conn., provides medical input and
      medical-educational collaboration in the evaluation and treatment of children
      experiencing learning and behavior problems. The program is staffed by two
      specially trained nurse practitioners, with consultation provided by
      pediatricians and a child psychologist. During its first year of operation,
      pediatric assessment was performed on 57 students at all three schools. Data
      analysis indicates that children were referred to the program for a broad range
      of concerns, that assessments were completed in a timely fashion, and that a
      variety of diagnoses were identified. Feedback from school personnel and parents
      suggests that the program offers a unique and valued pediatric perspective to the
      evaluation of school failure. Future plans include a more formal evaluation of
      the program's cost and effectiveness.

PMID- 8884664
TI  - Parents' self-reported behaviors related to health and safety of very young
      children.
AB  - This survey documented self-reported health and safety behaviors of parents of
      children enrolled in Head Start programs. The sample consisted of eight preschool
      programs (n = 1143) from different geographical areas of the country. This survey
      obtained baseline data on parent self-reported behavior as it relates to priority
      issues in child health and safety. A 25-item questionnaire assessed parents'
      behavior related to injury prevention, fire and electrical safety, firearm
      storage, poison prevention, automobile safety, and child supervision. More than
      90% of parents reported they use car seats, teach handwashing and pedestrian
      safety, and keep medicine and alcohol out of children's reach. Fewer than 60%,
      however, reported they keep guns and bullets stored separately and locked,
      possess a working fire extinguisher, or have the poison control telephone number
      available. Findings provide direction for emphasis for those developing or
      implementing a comprehensive family health education program.

PMID- 8884666
TI  - Effects of an inservice workshop on the health teaching self-efficacy of
      elementary school teachers.
AB  - This study examined the effectiveness of a 30-hour health education inservice
      training for elementary school teachers. Effectiveness was assessed by measuring
      pretest to post-test (eight months apart) differences in health teaching self
      efficacy, amount of time per week teaching health education, and amount of effort
      on specific health content areas. Workshop participants scored significantly
      higher than control teachers on efficacy expectations, outcome expectations, and
      outcome value subscales. Workshop participants also reported spending
      significantly more hours per week teaching health education and expending
      significantly more effort on a variety of specific health content areas than
      controls.

PMID- 8884667
TI  - Tobacco prevention in tobacco-raising areas: lessons from the lion's den.

PMID- 8884665
TI  - Factors in adolescent drinking/driving: binge drinking, cigarette smoking, and
      gender.
AB  - During three consecutive years, 3,137 high school seniors from three graduating
      classes in one Michigan county were surveyed. The primarily White sample reported
      their use of alcohol and cigarettes, driving experience, and drinking/driving
      experience. Survey data were linked with state driver history records. Fully one
      third of the high school seniors reported driving after drinking in the past six
      months. To identify factors associated with self-reported drinking/driving,
      correlation and regression analyses were conducted. Frequent binge drinking and
      riding with a drinking driver were consistent factors in driving after drinking
      frequency. Being male, smoking cigarettes, having frequent use of a motor
      vehicle, having a driving offense on record, and number of years licensed were
      important correlates, varying by year of graduation. Comprehensive interventions
      to moderate drinking, smoking, and driving after drinking are needed.

PMID- 8884668
TI  - Family history and premature coronary heart disease.
AB  - BACKGROUND: We were interested in studying whether a family history of coronary
      heart disease (CHD) persisted as a significant risk factor for premature coronary
      heart disease after adjusting for traditional and nontraditional risk factors.
      METHODS: Ninety-five case patients with documented premature CHD (occurring in a
      person less than 60 years old and with greater than 50 percent occlusion of a
      major epicardial vessel or a documented myocardial infarction) and 95 community
      based control patients were examined for risk factors including family history,
      hypertension, diabetes mellitus, sedentary lifestyle, smoking, body mass index,
      total cholesterol, high-density lipoprotein cholesterol, triglycerides, low
      density lipoprotein cholesterol, lipoprotein(a), homocysteine, and fibrinogen.
      RESULTS: The risk of premature CHD for a positive family history ranged from an
      odds ratio (OR) of 3.25 for a standard family history of CHD in a first-degree
      relative, 5.9 for family history of early CHD in a first-degree relative before
      the age of 45 years, and 6.1 for a strong family history of CHD defined as CHD in
      at least two first-degree relatives. Family history persisted as a significant
      risk factor for premature CHD (OR = 3.9, 95 percent confidence interval [CI] 1.8
      8.7) in multiple variable models that included traditional and nontraditional
      risk factors. It was rare, however, for a person with a positive family history
      not to have at least two other traditional or nontraditional risk factors.
      CONCLUSIONS: Family history of CHD should not be considered a simple binary risk
      factor for premature CHD, and a positive family history of CHD indicates that a
      person is at high risk for premature CHD independent of traditional and
      nontraditional risk factors.

PMID- 8884669
TI  - Supine infant sleep: what do family physicians recommend?
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) kills more than 6000 infants
      annually in the United States. Researchers have described prone sleep position as
      a risk factor for SIDS. A greater than 50 percent reduction in SIDS has been
      reported in countries where the predominant sleep position changed from prone to
      supine. In 1992 the American Academy of Pediatrics (AAP) recommended that healthy
      infants be placed in a supine position at bedtime. Previous studies of pediatric
      practices reported a 60 percent compliance with the recommendation. This study
      describes the self-reported compliance with the AAP recommendation by a cohort of
      family physicians. METHODS: Three hundred members of the Uniformed Services
      Academy of Family Physicians were mailed a questionnaire about their
      recommendations regarding infant sleep position. RESULTS: The response rate was
      77 percent. Sixty-two percent of the respondents usually or always encourage
      supine sleep position. Twenty-one percent usually or always discourage the supine
      sleep position. CONCLUSIONS: This cohort of family physicians encourages the
      supine sleep position at rates similar to reported cohorts of pediatricians.
      Reasons for the limited endorsement of the AAP recommendation were not explained
      by the results of this study.

PMID- 8884670
TI  - Etiology of chronic cough in a population of children referred to a pediatric
      pulmonologist.
AB  - BACKGROUND: Chronic cough is a common complaint encountered by physicians who
      care for children. It is also a common reason for referral to a pulmonologist.
      Determining the cause of chronic cough, however, rarely requires specialized
      diagnostic procedures that are unavailable to the primary care physician.
      METHODS: A computerized listing of new patients referred to a pediatric
      pulmonologist between July 1993 and June 1995 was reviewed. Of 299 patients
      examined as outpatients during this period, 95 were referred for chronic cough.
      The diagnosis and diagnostic procedures were examined to determine how frequently
      procedures available exclusively to subspecialists were necessary to determine
      the cause of chronic cough. RESULTS: Of the 95 patients who were examined for
      cough during the period studied, the diagnosis was made by history in 5,
      pulmonary function testing in 11, radiographic tests in 15, and a therapeutic
      trial in 58. In only 6 cases was the diagnosis made using tests unavailable to
      the primary care physician (5 bronchoscopy, 1 allergy skin testing). CONCLUSIONS:
      In 89 cases the cause of chronic cough was determined by procedures available to
      the referring physician. In most cases chronic cough in children can be diagnosed
      and managed by physicians who are aware of the spectrum of common disorders that
      lead to cough.

PMID- 8884671
TI  - Growth patterns of first-generation Southeast Asian Americans from birth to 5
      years of age.
AB  - OBJECTIVE: The objective of this study was to compare patterns of growth (height,
      weight, occipitofrontal circumference) of Hmong, Lao, and white children
      conceived and born in the United States. METHODS: The study design involved a
      retrospective review of longitudinal cohorts from clinic records. Participants
      included 146 white, 112 Hmong, and 49 Lao children on whom data were collected
      from birth to 5 years of age. All were patients of a community clinic in a poor
      urban neighborhood. The study included children whose mothers conceived and
      received all prenatal care in the United States and gave birth in Minnesota
      during a 10-year period. Measurements on family characteristics, height, weight,
      and occipitofrontal circumference were obtained. RESULTS: The white children
      generally approximate the medians of national (National Center for Health
      Statistics [NCHS]) reference data. Lao children (especially boys) are found to be
      short and proportionately light relative to reference data. Hmong children are
      found to be short relative to reference data but are disproportionately heavier,
      so that weight-for-height is considerably higher than reference data. In Hmong
      girls, mean weight-for-height z scores increase from -0.5 z at birth to 1.26 z at
      5 years, an average increase of 0.31 z per year. CONCLUSIONS: Lao and Hmong
      children conceived and born in the United States continue to have short stature
      (10th to 25th percentile). Hmong children have evidence of early overweight that
      is distinctive when compared with Lao and white counterparts.

PMID- 8884672
TI  - The mental health patient profile: does it change primary care physicians'
      practice patterns?
AB  - BACKGROUND: We conducted a prospective trial randomizing 75 physicians to either
      a control or intervention arm to evaluate the impact of providing patient
      reported information on anxiety and other mental health symptoms and disorders to
      primary care physicians. METHODS: Five hundred seventy-three patients of the
      study physicians who met entry criteria were randomized to either usual care or
      usual care supplemented with feedback of patient-reported mental health
      information to physicians. This mental health information was derived from
      initial patient-reported questionnaires completed in waiting rooms of physicians
      contracted to a mixed-model health maintenance organization in Colorado. Main
      outcome measures included impact of intervention on rates of (1) chart notation
      of anxiety, depression, or other mental health diagnoses or symptoms; (2)
      referral to mental health specialists; (3) prescription of psychotropic
      medications; (4) hospitalization; and (5) office visits during a 5-month
      observation period. RESULTS: Physicians receiving feedback on previously
      unrecognized and untreated anxiety patients were more likely to make chart
      notations (adjusted odds ratio [AOR] = 2.51, 95 percent confidence interval [CI]
      = 1.62-3.87), to make referrals to mental health specialists (AOR = 3.86, 95
      percent CI = 1.63-9.16), and to see patients for more frequent outpatient visits
      (AOR = 1.73, 95 percent CI = 1.11-2.70). Use of psychotropic medications and rate
      of hospitalizations did not differ significantly. CONCLUSIONS: Providing patient
      reported mental health information to primary care physicians resulted in
      increased recognition and referral rates for previously unrecognized and
      untreated anxiety patients, plus an increase in primary care visits, without
      concomitant increases in the use of psychotropic medications or rate of
      hospitalizations.

PMID- 8884673
TI  - The thoracic outlet syndrome in athletes.
AB  - BACKGROUND: The array of symptoms that characterize thoracic outlet syndrome
      (TOS) often lead to a failure or delay in diagnosing this condition in persons
      who are physically active. METHODS: Using the key words and phrases "thoracic
      outlet syndrome," "sport," "exercise," and "athlete," the MEDLINE files from 1991
      to April 1996 were searched. Articles dating before 1991 were accessed by cross
      referencing the more recent articles. RESULTS AND CONCLUSIONS: TOS results from
      compression of the neural or vascular structures of the upper extremity at the
      thoracic outlet. Clinical manifestations can include upper extremity pain,
      paresthesias, numbness, weakness, fatigability, swelling, discoloration, and
      Raynaud phenomenon. Four symptom patterns have been described: upper plexus,
      lower plexus, vascular, and mixed. The lower brachial plexus pattern is the most
      common. Specific causes of outlet compression include injury to the scalene or
      scapular suspensory muscles, anomalous fibromuscular bands, cervical ribs,
      clavicular deformity, and pectoralis minor tendon hypertrophy. The diagnosis of
      TOS is established on the results of the history and physical examination.
      Ancillary studies are most helpful to rule out other conditions rather than
      confirm the diagnosis of TOS. In most cases the initial treatment is nonoperative
      with an emphasis on rehabilitative exercises for the neck and shoulder girdle.
      Surgery is indicated for acute vascular insufficiency, progressive neurologic
      dysfunction, and refractory pain that fails conservative treatment. The surgical
      technique involves the release or removal of the structures that cause
      compression and can involve scalene muscle release, first rib resection, cervical
      rib excision, and resection of fibromuscular bands.

PMID- 8884674
TI  - Hyperreactive malarial syndrome.

PMID- 8884675
TI  - Physician payment and the game of risk.

PMID- 8884676
TI  - Clinical practice guideline panels: personal experience.

PMID- 8884677
TI  - Maternal postpartum thyroiditis as infant growth failure.

PMID- 8884678
TI  - Rapidly progressive prostate cancer in the primary care setting.

PMID- 8884679
TI  - Card of thanks: a personal note on the physician-patient relationship.

PMID- 8884680
TI  - Is heart disease all in the family? Family history and cardiovascular disease.

PMID- 8884681
TI  - Opioid therapy and chronic low back pain.

PMID- 8884682
TI  - Opioid therapy and chronic low back pain.

PMID- 8884683
TI  - Opioid therapy and low back pain.

PMID- 8884684
TI  - Opioid therapy and low back pain.

PMID- 8884685
TI  - The dynamically evolving field of cervical cancer screening.

PMID- 8884686
TI  - Management of hepatitis C.

PMID- 8884687
TI  - Caring for deaf patients.

PMID- 8884688
TI  - NIH consensus on Helicobacter pylori in peptic ulcer disease.

PMID- 8884689
TI  - CNS-mediated influence of TRH and its analog, NS-3, on the function of the rabbit
      lower urinary tract.
AB  - The effects of thyrotropin-releasing hormone (TRH) and its new analog, NS-3
      (montireline), on the lower urinary tract in rabbits were investigated. TRH and
      NS-3 elicited transient increases in intravesical pressure and micturition. They
      also caused long-lasting increases in intraurethral pressure and EMG activity of
      the external urethral sphincter, which were not affected by prazosin or
      transection of the hypogastric nerve, but were eliminated by transection of the
      pudendal nerve. In animals decerebrated at the supracollicular post-mammillary
      level, these drugs did not increase intravesical pressure or micturition, but
      they did elicit increases in intraurethral pressure and sphincter EMG activity.
      No binding sites for TRH were found in the lower urinary tract. These findings
      suggest that the sites of action of TRH and NS-3 which elicit intravesical
      pressure increase or micturition might be located in the area rostral to the
      pons, and that the sites of action which elicit increases in intraurethral
      pressure and sphincter EMG activity might be located caudal to the rostral pons.

PMID- 8884690
TI  - Loss of [125I]-pindolol binding to beta-adrenoceptors on rat nodose ganglion
      after chronic isoprenaline treatment.
AB  - The nodose ganglion contains the cell bodies of afferent nerves which convey
      predominantly sensory information from the viscera to the central nervous system
      (CNS). Autoradiographic studies show binding sites for beta-adrenoceptor ligands
      are present on sections of the rat nodose ganglion and also on the corresponding
      inferior vagal ganglion in humans, indicating the presence of beta-adrenoceptors
      in these ganglia. Since prolonged stimulation of beta-adrenoceptors in rats with
      the nonselective beta-adrenoceptor agonist isoprenaline (400 micrograms kg-1 day
      1 s.c.) for 14 days results in desensitisation and/or down-regulation of
      receptors in peripheral tissues, such as heart, kidney and blood vessels, the
      effects of this treatment on the beta-adrenoceptor population on the nodose
      ganglion have been examined. Using [125I]-pindolol as a radioligand,
      autoradiographic studies revealed that specific binding was reduced by 74% in
      ganglia from isoprenaline-pretreated rats compared to that in ganglia from
      vehicle-pretreated rats, demonstrating down-regulation of receptors by
      isoprenaline. [125I]-Pindolol binding was sensitive to inhibition by ICI 118.551
      (selective beta 2-adrenoceptor antagonist) but not to atenolol (selective beta 1
      adrenoceptor antagonist), indicating receptors are predominantly of the beta 2
      adrenoceptor subtype. No change in binding was apparent over the vagus nerve. The
      nodose ganglion appears to be an additional site at which beta 2-adrenoceptors
      may be down-regulated in vivo, possibly interfering with normal baro-, chemo- and
      sensory reflexes.

PMID- 8884691
TI  - Effects of stress and hypophysectomy on the uptake of [3H]2-deoxy-D-glucose in
      the mouse adrenal medulla: an autoradiographic study.
AB  - Effects of immobilization stress and hypophysectomy on the uptake of [3H] 2-deoxy
      D-glucose (2DG) in the adrenal medulla of the mouse was examined by
      autoradiography. Radioactivity due to [3H]2DG in both adrenaline-storing and
      noradrenaline-storing cells was markedly increased by acute immobilization
      stress. Under immobilization stress, adrenaline-storing cells incorporated more
      2DG than noradrenaline-storing cells. Adrenal denervation did not change the
      uptake of 2DG either in control or in stressed adrenal medulla. The uptake of
      [3H]2DG was also increased by hypophysectomy. Since withdrawal of cortical
      steroid hormones enhanced the uptake of 2DG and the adrenal denervation did not
      change the uptake, it is suggested that certain substances, such as bradykinin or
      histamine, which are released on immobilization stress from certain tissues other
      than sympathetic nerve endings in the medulla, enhanced the uptake of [3H]2DG.
      This phenomenon occurs mainly in adrenaline-storing cells.

PMID- 8884692
TI  - Baroreceptor modulation of regional haemodynamic responses to acute stress in
      rat.
AB  - We examined the effects of chronic sinoaortic denervation (SAD) on regional
      haemodynamic responses to acute environmental stress in rats. In conscious male
      intact (n = 12) and SAD (2 weeks before study, n = 7) rats, arterial pressure and
      blood flow velocities (pulsed Doppler probes) in the subdiaphragmatic aorta,
      superior mesenteric artery and distal aorta (hindquarters) were simultaneously
      recorded. In response to air jet stress, intact rats showed modest increases in
      arterial pressure that were accompanied by vasoconstriction in the mesentery and
      vasodilatation in the hindquarters. These regional haemodynamic changes were
      almost balanced, as indicated by the lack of change in the subdiaphragmatic
      aortic conductance. SAD markedly enhanced the pressor and mesenteric
      vasoconstrictor responses and blunted the hindquarters vasodilatation. After
      acute beta-adrenoceptor blockade with propranolol, the stress-induced
      hindquarters vasodilatation was strongly reduced in the intact rats and was
      reversed into vasoconstriction in the SAD rats. These results point to an
      opposing interaction between centrally-induced sympathoexcitation and arterial
      baroreceptor reflex activation during stress. This probably favours the
      hyperaemic response in the skeletal muscles at a lower metabolic cost.

PMID- 8884693
TI  - Characterization of the membrane conductance changes underlying the apamin
      resistant NANC inhibitory junction potential in the guinea-pig proximal and
      distal colon.
AB  - The nature of the electrically- or stretch-evoked nonadrenergic, noncholinergic
      (NANC) inhibitory junction potentials (IJPs) in circular smooth muscle cells of
      the guinea-pig proximal and distal colon were investigated using standard
      intracellular microelectrode recording techniques. We have confirmed that the
      NANC IJP, recorded in the presence of hyoscine (1 microM) and nifedipine (1
      microM), can be divided into two components with apamin (250 nM), a blocker of
      the small conductance Ca2(+)-activated K+ channels. Both the apamin-sensitive and
      the apamin-resistant components of the IJP were blocked by tetrodotoxin (1.6
      microM) or by lowering the external Ca2+ concentration (to 0.25 mM). The apamin
      sensitive IJP was also blocked by omega-conotoxin GVIA (100 nM), a blocker of 'N
      type' Ca2+ channels. The apamin-resistant IJP and rebound post-stimulus
      depolarization (PSD) were reduced upon exposure to either NG-L-arginine (NOLA),
      an inhibitor of nitric oxide synthase (NOS), or the nitric oxide (NO) scavenger,
      haemoglobin. The effects of NOLA were partially reversed in the presence of
      excess L-arginine, a substrate for NOS, suggesting that NO, or a related NO-donor
      compound, is likely to be the apamin-resistant inhibitory transmitter. Blockade
      of either the apamin-sensitive or apamin-resistant IJP was associated with
      membrane depolarization and a decrease in the membrane conductance in the absence
      of nerve stimulation. In the proximal colon, the apamin-resistant IJP and PSD
      could both be demonstrated to arise from an increase in the membrane conductance
      after subtraction of a non-linear background conductance. The hyperpolarization
      upon repetitive NANC nerve stimulation was mimicked by the NO donor, S-nitroso-L
      cysteine (2.5-25 microM), which evoked a transient apamin-sensitive, but omega
      conotoxin GVIA resistant, component followed by a slower apamin-resistant
      component. These results suggest that neurally-released NO has a number of
      actions in the guinea-pig colon, causing apamin-resistant hyperpolarization and
      depolarization, as well as directly opening apamin-sensitive K+ channels.

PMID- 8884694
TI  - Assessment of autonomic nervous function by power spectral analysis of heart rate
      variability in the horse.
AB  - We studied power spectral analysis of heart rate (HR) variability in the horse,
      with the hypothesis that the quantitative information provided by the spectral
      analysis of HR variability reflects the interaction between sympathetic and
      parasympathetic regulatory activities. For this purpose, electrocardiogram, blood
      pressure (BP) and respiratory (Resp) waveform were simultaneously recorded from
      Thoroughbred horses (3-5 years old) and analyzed by power spectrum. There were
      two major spectral components at low-frequency (LF) and high-frequency (HF) bands
      for HR variability. The peak of Resp variability clearly occurred at the HF
      range. In contrast to Resp variability, the power spectra of BP variability
      occurred at lower frequencies. The maximum coherence between HR and Resp
      variabilities and HR and BP variabilities occurred at approximately 0.15 and
      approximately 0.03 Hz, respectively. These relationships were similar to the
      ensemble spectra. On the basis of these data, we have defined two frequency bands
      of interest: LF (0.01-0.07 Hz) and HF (0.07-0.6 Hz). Therefore, we believe that
      power spectral analysis of HR variability provides a very powerful technique for
      assessing autonomic nervous activity in the horse.

PMID- 8884695
TI  - Sympathetic and VIP-ergic control of calcium and bicarbonate transport in the
      feline gall bladder mucosa in vivo.
AB  - The regulation of calcium ion absorption by the gall bladder mucosa may be
      important for gall stone formation but this process is poorly understood. In this
      study performed in anaesthetized cats, the gail bladder lumen was perfused by a
      buffer equilibrated with 4% CO2 in air. During basal conditions, the pH and the
      [Ca2+] x [CO3(2-)] ion product decreased in the buffer when passing through the
      gall bladder lumen. The net absorption of calcium ions and fluid was
      significantly enhanced by stimulation of the splanchnic nerves. Intravenous
      infusion of vasoactive intestinal peptide (VIP) increased pH and the [Ca2+] x
      [CO3(2-)] ion product significantly in the buffer during the passage through the
      gall bladder lumen. Moreover, the basal fluid absorption was reversed to a net
      fluid secretion. In view of the presence of noradrenergic and VIP-immunoreactive
      nerve fibres in the gall bladder wall, and VIP-receptors on the gall bladder
      epithelial cells, the study suggests the existence of neural control mechanisms
      influencing the transport of Ca2+ by the gall bladder mucosa. These may be
      important to reduce potential calcium lithogenicity in the gall bladder lumen.

PMID- 8884696
TI  - Assessment of sympathetic nerve activity in the practice of lumbar sympatholysis:
      interest of sympathetic skin responses.
AB  - The place of lumbar sympathectomy in the treatment of occlusive arterial disease
      of the lower limbs remains controversial. An adequate assessment of sympathetic
      nerve function in the practice of sympathectomy may reduce unsatisfactory results
      of this procedure. We report a series of 25 lumbar sympatholyses indicated for
      claudication, rest pain or distal arterial ulcer, and attempted by means of
      phenol injection in sympathetic ganglia under tomographic guidance. Sympathetic
      skin response (SSR) recording, an electrophysiological test of sympathetic
      activity, was performed before and after phenol injection, and its results were
      compared to the clinical outcome. SSR was abolished in the treated limb after
      phenol injection in only 64% of the cases. The post-injection abolition of SSR
      was correlated with the clinical improvement rate: 11% when SSR was still
      present, but 75% when SSR was abolished. In this latter case, the pre-injection
      values of SSR amplitudes could predict the clinical benefit of sympatholysis. It
      is necessary to assess the sympathetic activity in a limb before and after doing
      sympatholysis. Preoperatively, this activity may be diminished or already
      abolished in patients suffering from neuropathy involving the autonomic nervous
      system, limiting the indication of sympathectomy. Postoperatively, if sympathetic
      activity is still present in the treated limb, it implies that the sympathectomy
      is not completed, and it supports the indication of a new sympatholysis attempt.
      These observations show the usefulness of SSR recording in the practice of phenol
      sympatholysis, this test being simple and specific of sympathetic nerve function.

PMID- 8884697
TI  - Antihypertensive treatment and heart rate variability in diabetic patients: role
      of cardiac autonomic neuropathy.
AB  - Optimization of antihypertensive drug therapy continues to be a clinical
      challenge in patients with diabetes mellitus and its complications. We assessed
      the interference of autonomic neuropathy with drug effects on heart rate
      variability in 13 hypertensive diabetic subjects (mean age 48.4 years) during
      treatment with two blood pressure lowering drugs, metoprolol and enalapril. The
      baseline findings were compared with those obtained in 24 diabetic subjects
      without hypertension (mean age 32.5 years) and in 24 non-diabetic hypertensive
      patients (mean age 47.6 years). Cardiovagal autonomic neuropathy was present in
      10/13 (77%) of the hypertensive diabetic group, 14/24 (58%) the non-hypertensive
      diabetic group and 17/24 (71%) the non-diabetic hypertensive group. Heart rate
      variation was studied by power spectral analysis using total variability and
      three different frequency bands (low-frequency 0.025-0.075 Hz, mid-frequency
      0.075-0.15 Hz and high-frequency 0.15-0.40 Hz). At baseline, the two hypertensive
      groups showed significantly smaller mid- and high-frequency heart rate
      variability compared with the diabetes only group. Age and the presence of
      cardiovagal autonomic neuropathy were important determinants of variability. Both
      metoprolol and enalapril reduced blood pressure comparably in hypertensive
      diabetics while metoprolol also reduced heart rate. Metoprolol decreased heart
      rate variability at the low-frequency and mid-frequency bands even after
      correction for the change in heart rate. Heart rate variability was not
      significantly altered by enalapril. In subjects with hypertension, diabetes and
      autonomic neuropathy, metoprolol almost abolished all heart rate variability.
      Therefore, an ACE inhibitor is a more neutral treatment alternative in such
      patients from the point of view of autonomic cardiac control.

PMID- 8884698
TI  - Non-neurogenic periodic fluctuations in heart rate and vasomotion appearing in
      familial amyloid polyneuropathy (FAP) Type I (Met30).
AB  - In order to evaluate the function of the autonomic nervous system, power spectral
      analysis of heart rate fluctuation and waveform observation of cutaneous
      vasomotion were conducted in 3 patients with familial amyloid polyneuropathy Type
      1 (FAP) (Met30) with autonomic disorders. In 2 FAP patients in the early stage,
      both high (HFC: 0.12-0.4 Hz) and low frequency components (LFC: 0.04-0.12 Hz) in
      the heart rate spectrum, and basic (BW) and reflex waves (RW) in the vasomotion
      were all markedly suppressed. However, in an FAP patient in the advanced stage,
      prominent spectral peaks were recognized in both the spectral bands of LFC and
      HFC. HFCs were neither correspondent with the respiratory frequency nor depressed
      by atropine, and BW was not affected by acute denervation using a local
      anesthetic. RW was absent irrespective of the denervation. These results suggest
      that the denervated heart and vascular smooth muscles might have newly acquired
      periodic fluctuations, although the physiological mechanism and meanings remain
      to be investigated.

PMID- 8884699
TI  - Differential regional sympathetic responses to somatic stimulation in
      anesthetized dogs.
AB  - The present study was designed to determine whether regional differences exist in
      sympathetic responses to somatic nerve stimulation and whether the baroreceptor
      reflex modulates this somato-sympathetic reflex. The cardiac (CNA), renal (RNA),
      hepatic (HNA), splenic (SpNA) and adrenal (AdNA) sympathetic postganglionic nerve
      activities (SNA) were simultaneously recorded in anesthetized dogs with intact (n
      = 7) or bilaterally sectioned (n = 8) carotid sinus and vagus nerves. In the
      intact group, electrical stimulation of the left peroneal nerve at low intensity
      and low frequency (5 V, 5 Hz) produced a fall in mean arterial pressure (MAP) (
      9.7 +/- 2.7 mmHg) and a decrease in each SNA with no regional differences RNA
      (79.2 +/- 8.5%), AdNA (82.7 +/- 5.4%), HNA (89.4 +/- 4.5%), CNA (87.5 +/- 3.5%),
      SpNA (84.2 +/- 3.2%). In contrast, stimulation at high intensity and high
      frequency (25 V, 50 Hz) produced a rise in MAP (+21.4 +/- 3.8 mmHg) and increases
      in SNA with quantitative predominance of RNA (178.6 +/- 13.6%) and AdNA (158.3 +/
      16.1%) over HNA (129.0 +/- 4.2%), CNA (117.7 +/- 7.6%), and SpNA (112.0 +/-
      6.2%). Similar responses were observed when the left ulnar nerve was stimulated.
      The changes in SNA (delta SNA) at 10 s after the start of stimulation were
      plotted as a function of the changes in MAP (delta MAP) and the regression curves
      were determined. The best fit regression curve was a logistic sigmoid curve in
      the intact group and a linear one in the baroreceptor denervated group.
      Furthermore, delta RNA/delta MAP and delta AdNA/delta MAP during the somato
      pressor response were significantly smaller in the intact group than in the
      denervated group. In conclusion, there are regional differences of sympathetic
      response during the somato pressor response but not during somato depressor
      response. The baroreceptor reflex may suppress the somato-sympathetic reflex of
      RNA and AdNA.

PMID- 8884700
TI  - Is the heart "empty' at syncope?
AB  - Neurally-mediated syncope (NMS) is thought to be reflexly triggered by vagal
      cardiac ventricular afferents that are activated by impaired cardiac filling. If
      this hypothesis is true then maneuvers that increase venous pooling should
      progressively diminish cardiac volume triggering syncope once a threshold
      decrease in cardiac filling is reached. Beat-to-beat recordings of heart rate,
      blood pressure (Finapres) and stroke volume (impedance cardiograph) were made at
      rest and during head-up tilt (80 degrees) in twenty controls and in fourteen
      patients with recurrent NMS (group 1). Hemodynamic profiles of controls and group
      1 were compared. In eleven additional patients with NMS (group 2) we measured
      cardiac chamber volume from apical two or four-chamber views or stroke volume
      from Doppler measurements of the left ventricular outflow tract at rest and
      during tilt. Baseline values and initial response to head-up tilt of controls and
      group 1 patients were similar. A small negative trend in blood pressure and total
      peripheral resistance was present for at least 250 s before the onset of syncope.
      Stroke volume remained stable during this presyncopal period and increased at
      syncope. The profile of stroke volume changes using impedance cardiography
      mirrored those obtained using Doppler (5 subjects). Reliable echocardiographic
      measurements of cardiac chamber size were obtained in five subjects and did not
      change during tilt, presyncope or syncope. These data show that there is no
      significant decrease in cardiac volume before syncope that could serve as a
      trigger of syncope.

PMID- 8884701
TI  - Preservation of the cervical vagus nerve in aged rats: morphometric and enzyme
      histochemical evidence.
AB  - The vagus nerve trunk, sampled at a mid-cervical level, has been analysed
      quantitatively by light and electron microscopy principally with respect to the
      numbers and sizes of the myelinated and unmyelinated axon populations in Wistar
      rats of 4, 24 and 30 months. No significant differences in total myelinated axon
      numbers were seen over the age range in counts made on light microscope montages
      of the entire cross-section of the nerve. The overall histological organisation
      and appearance of the nerve trunk did not change with age but age-associated
      alterations in the ultrastructure of some myelinated fibres and their Schwann
      cells was seen. Unmyelinated axons and their associated Schwann cells rarely
      showed age-associated changes. The numbers of myelinated and unmyelinated axons
      per mm2 determined from electron micrographs were, however, slightly decreased
      but the ratio of myelinated to unmyelinated axons was approximately 1:4 at all
      ages. Measurements of myelinated fibres showed a small but significant increase
      in size between young and old animals. There was an increase in the thickness of
      the myelin sheath, a decrease in myelinated axon diameter and in the the g ratio.
      The diameter of unmyelinated axons decreased with age and the number of
      unmyelinated axons per Schwann cell unit increased. The numbers, diameters and
      thickness of the walls of the vagal microvessels remained unchanged. Quantitation
      by microdensitometry of the activity of NADH tetrazolium reductase and succinate
      dehydrogenase in longitudinal sections of the vagus indicated an increase in the
      activity of these two metabolic markers whilst an increase in the activity of
      cytochrome oxidase indicated that neuronal activity in the vagus was unimpaired
      in old age. It is concluded that the structure of the rat vagus nerve, and in
      particular of its predominantly unmyelinated axon population, is not
      significantly affected in old age.

PMID- 8884703
TI  - Pedicle screw instrumentation for unstable thoracolumbar fractures.
AB  - We evaluated the results of short-segment pedicle screw instrumentation in 54
      patients with unstable thoracolumbar fractures. Follow-up averaged 25 months
      (range, 11 to 36 months); 42 patients completed the study. Kyphosis was corrected
      by an average of 7 degrees at surgery and loss of correction averaged 5 degrees
      at the end of follow-up. On computed tomography, canal compromise averaged 57%
      preoperatively and 33% postoperatively. Complications included nerve root
      irritation due to screw penetration (1/42), screw breakage (2/42), and screw
      bending (6/42). Solid fusion was achieved in all cases at an average of 3 months.
      Of the 31 patients with normal neurologic function, 24 (77%) were pain-free at
      follow-up and had returned to previous levels of activity. We conclude that short
      segment fixation with posterolateral fusion is effective in the treatment of
      unstable thoracolumbar fractures; it prevents progression of kyphotic deformity
      and neurologic deterioration, results in a stable fusion, and preserves
      uninvolved motion segments above and below the fracture site.

PMID- 8884704
TI  - Indications for laser surgery in the treatment of degenerative disk disease of
      the lumbar spine.
AB  - Percutaneous laser diskectomy has recently been promoted as a viable alternative
      in treatment of the symptomatic lumbar disk herniation. Careful scrutiny of the
      literature, including the natural history of low back disorders and results of
      various surgical techniques in controlled studies, makes it clear that
      percutaneous laser diskectomy adds little to our surgical armamentarium. As
      surgeons, we should be encouraged to make treatment decisions in the best
      interests of our patients, based on unbiased, prospective scientific studies.

PMID- 8884705
TI  - Deep vein thrombosis in lumbar spinal fusion: a prospective study of antiembolic
      and pneumatic compression stockings.
AB  - We prospectively studied the incidence of deep vein thrombosis (DVT) of the thigh
      in 117 patients having posterior lumbar spinal fusion with instrumentation and
      bone grafting for degenerative disk disease or spondylolisthesis. Patients with
      neoplasm, infection, trauma, or history of DVT were excluded. Patients were
      randomized into two groups. In the operating room, group 1 patients were placed
      in thigh-high antiembolic compression stockings (TED hose), and group 2 patients
      were placed in antiembolic stockings and pneumatic compression stockings. In both
      groups, the stockings were used until discharge. Postoperatively, patients in
      both groups received 600 mg buffered aspirin twice daily. Comparative analysis of
      the two groups showed no difference in operative time, blood loss, number of
      levels of lumbar vertebrae fused, time to mobilization, weight, age, or sex. All
      patients had duplex scanning of the thigh postoperatively. No patient in the
      series was observed to have acute DVT by clinical examination or by
      ultrasonography.

PMID- 8884706
TI  - Mattresses and sleep for patients with low back pain: a survey of orthopaedic
      surgeons.

PMID- 8884709
TI  - Diagnosis and indications for elective spinal surgery.

PMID- 8884708
TI  - Nonoperative treatment of degenerative cervical disk disease.
AB  - The therapeutic goal in treating patients with degenerative neck pain is prompt
      return to normal activity with the least diagnostic and therapeutic expense.
      Although many noninvasive treatment modalities exist, most are based on
      empiricism and tradition and lack scientific validation. With few exceptions,
      degenerative cervical pain syndromes require an initial period of conservative
      therapy, since their natural course favors spontaneous resolution. Patients with
      a clinical history suggestive of either progressive myelopathy, infection, or
      malignancy warrant more aggressive initial assessment and treatment.

PMID- 8884707
TI  - Operative treatment of degenerative cervical disk disease.
AB  - The surgical treatment of degenerative cervical disk disease should be considered
      only after an adequate trial of conservative management has failed. When surgery
      is contemplated, the decision must be based on sound indications and the
      operative strategy and approach must address the specific abnormality responsible
      for the patient's symptom complex.

PMID- 8884710
TI  - Causes and management of unstable degenerative spinal stenosis.

PMID- 8884711
TI  - Treatment of adult scoliosis.

PMID- 8884712
TI  - Exercise and immunity: a review with emphasis on the horse.
AB  - Exercise has been recognized as a stress, which can significantly alter the
      host's immune response and, therefore, its susceptibility to disease. Whereas
      research in this area has previously focused primarily on human subjects and
      laboratory animals, it has more recently extended to domestic animals, especially
      the equine athlete. Despite several studies, defining the relationship among
      exercise, the immune response, and disease has proven difficult due to a number
      of factors, including the complexity of the immune system and the variable nature
      of exercise itself. It now appears that exercise has dual effects on the immune
      system. Suppressive effects, such as a decline in the ratio of CD4+ to CD8+
      cells, diminished lymphocyte function, and a decline in the number and cytolytic
      activity of natural killer cells have been observed in response to brief high
      intensity exercise, prolonged exhaustive exercise, and overtraining. In contrast,
      moderate training generally has beneficial effects on host defense mechanisms.
      The mechanisms for regulating the dual effects of exercise are complex, involving
      a network of neuroendocrine hormones and cytokines.

PMID- 8884713
TI  - Vaccine-associated immune-mediated hemolytic anemia in the dog.
AB  - Vaccination has been incriminated as a trigger of immune-mediated hemolytic
      anemia (IMHA) in dogs and in people, but evidence to support this association is
      lacking. In a controlled retrospective study, idiopathic IMHA was identified in
      58 dogs over a 27-month period. When compared with a randomly selected control
      group of 70 dogs (presented for reasons other than IMHA) over the same period,
      the distribution of cases versus time since vaccination was different (P < .05).
      Fifteen of the dogs (26%) had been vaccinated within 1 month (mean, 13 days;
      median, 14 days; range, 1 to 27 days) of developing IMHA (P < .0001), whereas in
      the control group no marked increase in frequency of presentation was seen in the
      first month after vaccination. The dogs with IMHA were divided into 2 groups
      based on time since vaccination: the vaccine IMHA group included dogs vaccinated
      within 1 month of developing IMHA; the nonvaccine IMHA group included dogs that
      developed IMHA more than 1 month after vaccination. The recently vaccinated dogs
      with IMHA (vaccine IMHA group) had significantly lower platelet counts (P < .05)
      and a trend towards increased prevalence of intravascular hemolysis and
      autoagglutination when compared with the nonvaccine IMHA group. Similar mortality
      rates were seen in teh vaccine IMHA group (60%) and the nonvaccine IMHA group
      (44%), with the majority of fatalities (> 75%) occurring in the first 3 weeks
      after presentation. Persistent autoagglutination was a negative prognostic
      indicator for survival in both groups (P < .05). Presence of icterus and
      hyperbilirubinemia were negative prognostic indicators for survival in the
      nonvaccine IMHA group (P < .0001 and P < .01, respectively) but not in the
      vaccine IMHA group. In the recently vaccinated dogs, combination vaccines from
      various manufacturers against canine distemper, adenovirus type 2, leptospirosis,
      parainfluenza, and parvovirus (DHLPP) were involved in each case. Vaccines
      against rabies virus, Bordetella spp, coronavirus, and Lyme Borrelia were
      administrated concomitantly to some dogs. This study provides the first clinical
      evidence for a temporal relationship of vaccine-associated IMHA in the dog.

PMID- 8884714
TI  - Sonographic evaluation of the common bile duct in cats.
AB  - Ultrasound is an excellent imaging tool in the evaluation of the biliary tract in
      cats. Extrahepatic obstruction could be diagnosed by the presence of dilated
      common bile duct (CBD), which was measured ventral to the portal vein in the
      porta hepatis. At this level, the diameter of the CBD in 6 healthy cats and in 22
      cats with nonsurgical jaundice was < or = 4 mm. Six of 7 cats with a CBD > 5 mm
      had extrahepatic biliary obstruction.

PMID- 8884715
TI  - The effect of hetastarch on serum colloid oncotic pressure in hypoalbuminemic
      dogs.
AB  - The purpose of this study was to determine the duration of action of a single
      dose of hetastarch, a synthetic colloid, in hypoalbuminemic dogs. Thirty
      hypoalbuminemic dogs (albumin concentration, < or = 2.0 g/dL) received 1 dose of
      hetastarch each, with an average dose of 18.1 mL/kg. Doses ranged from 7.7 to
      43.9 mL/kg, with the majority of doses (n = 26) in the range of 10 to 25 mL/kg.
      Dogs were allotted to one of several groups: all dogs, dogs with acute
      gastrointestinal protein loss, dogs with chronic gastrointestinal protein loss,
      all dogs with gastrointestinal protein loss, and dogs with nongastrointestinal
      protein loss. Colloid oncotic pressure was measured immediately before and
      immediately after hetastarch administration, and 12 hours after hetastarch
      administration. There was a significant (P < .001) increase in the mean colloid
      oncotic pressure after hetastarch treatment in all groups, except in the group
      with acute gastrointestinal protein loss. Twelve hours after hetastarch
      treatment, the mean colloid oncotic pressure had decreased significantly (P <
      .001) from the immediate post-treatment value in all groups, except in dogs in
      the groups with acute and chronic gastrointestinal protein loss. Twelve hours
      after hetastarch treatment the mean colloid oncotic pressure was not
      significantly (P < .001) different from the baseline mean colloid oncotic
      pressure in any of the groups. Twenty-three dogs (77%) survived their illness and
      were sent home, whereas, 7 (23%) died or were euthanized. The effect of a single
      dose of hetastarch on raising colloid oncotic pressure in dogs with
      hypoalbuminemia decreases significantly within 12 hours of administration, and is
      no longer significantly above baseline values. We conclude that multiple dosing
      is necessary to prolong the beneficial effects of hetastarch.

PMID- 8884716
TI  - Evaluation of 3 assays for failure of passive transfer in calves.
AB  - This study examined the sensitivity, specificity, predictive values, and
      classification accuracy of 3 commonly used screening tests for failure of passive
      transfer: the sodium sulfite turbidity test, the zinc sulfate turbidity test, and
      refractometry relative to serum immunoglobulin G1 (IgG1) concentrations
      determined by radial immunodiffusion. Serum samples were obtained from 242 calves
      ranging from 1 to 8 days of age. Using a serum concentration of 1,000 mg/dL IgG1,
      to define adequate passive transfer, the zinc sulfate test had a sensitivity of
      1.00 and a specificity of 0.52 in the detection of inadequate passive transfer.
      The endpoint of the test appeared to be higher than desired; calves testing
      negative had mean serum IgG1 concentration of 955 mg/dL and a large proportion of
      calves with adequate passive transfer were misclassified as positive for failure
      of passive transfer. Using the qualitative zinc sulfate test, the percentage of
      calves correctly classified with regard to passive transfer status was less than
      that observed with either the sodium sulfite test or refractometry. The
      sensitivity of the sodium sulfite assay was 0.85 at a 1+ endpoint and 1.00 at a 2
      or 3+ endpoint. The specificity of the sodium sulfite assay varied from 0.87 at a
      1+ endpoint and 0.56 at a 2+ endpoint. The sensitivity and specificity of
      refractometry varied from 0.01 to 1.00 depending on the choice of endpoint.
      Refractometry correctly classified the largest proportion of calves with regard
      to their passive transfer status at test endpoints of 5.0 and 5.5 g/dL, 83% and
      82% respectively. The highest percentages of calves correctly classified occurred
      with the sodium sulfite test using a 1+ endpoint (86.30%) and refractometry using
      a 5.0 g/dL endpoint (83.00%). A regression equation was developed that permitted
      calculation of an optimal endpoint for refractometric determinations of total
      serum protein concentration. A serum protein concentration of 5.2 g/dL was
      equivalent to 1,000 mg/dL serum IgG1. Optimal selection of tests for passive
      transfer status in calves will be governed by the prevalence of failure of
      passive transfer, test performance, and the anticipated costs of classification
      errors.

PMID- 8884717
TI  - Hepatobiliary scintigraphy in the evaluation of feline liver disease.
AB  - Hepatobiliary scintigraphy (HBS) was performed in 10 cats with histologically
      documented hepatobiliary disease. The scintigraphic patterns were classified into
      one of 5 categories: normal, primary hepatocellular dysfunction, primary
      intrahepatic cholestasis, mixed hepatocellular and intrahepatic cholestasis, and
      extrahepatic obstructive patterns. Initial attempts were made to correlate
      specific disease entities with HBS patterns, but a consistent relationship could
      not be determined. A correlation between the histological severity of a given
      hepatic disease and the HBS pattern was made. All cats (n = 5) with a mixed
      hepatocellular and intrahepatic cholestasis scintigraphic pattern with normal
      gallbladder function had a histologically severe form of their individual hepatic
      disease. Three of the 4 cats with an intrahepatic cholestasis pattern and normal
      hepatocellular and gallbladder function had histologically mild or moderate forms
      of their individual hepatic diseases. One cat had an extrahepatic obstructive
      pattern where no radiopharmaceutical was identified in the gallbladder or small
      intestine by 3 hours postinjection. This study suggests that HBS can be useful in
      cats with hepatobiliary disease to assess the severity of hepatic dysfunction,
      and to determine if extrahepatic biliary obstruction is present. Correlation
      between HBS patterns and specific disease entities such as hepatic lipidosis or
      cholangitis-cholangiohepatitis syndrome could not be made in this study.

PMID- 8884718
TI  - Pharmacokinetic and pharmacodynamic properties of conventional and CD-formulated
      diltiazem in cats.
AB  - The i.v. and apparent steady-state kinetics of diltiazem HCI (DLT) and slow
      absorption long-acting diltiazem (CD) given p.o. were investigated in cats. The
      effects of p.o. diltiazem on heart rate and PR interval were also studied. Plasma
      diltiazem concentrations were determined by ultraviolet high-performance liquid
      chromatography (UV-HPLC), using verapamil as the internal standard. Heart rate
      and PR interval determinations were evaluated over a 24-hour period for the PO
      formulations and compared with values under diltiazemfree conditions. The mean
      systemic clearance and apparent volume of distribution of i.v. diltiazem were
      15.0 mL/min/kg and 2.70 L/kg, respectively. The elimination half-life of
      diltiazem after i.v. and p.o. DLT administration were approximately 120 minutes.
      In contrast, the terminal half-life of CD was 460 minutes. The mean apparent
      bioavailability of DLT p.o. was 71%, which was significantly higher than that
      observed with CD (36%). Heart rate and PR intervals in cats receiving the 2
      formulations at steady-state were not different from those measured in the drug
      free state. We conclude that DLT at 1 mg/kg p.o. tid and CD at 10 mg/kg p.o. sid
      provide plasma concentrations that are known to have pharmacodynamic effects in
      other species.

PMID- 8884719
TI  - Fibronectin concentrations in pleural and abdominal effusions in dogs and cats.
AB  - A commercial nephelometric test kit for human fibronectin (FN) was found suitable
      for the estimation of fibronectin concentration in body effusions of cats and
      dogs. The FN measurements were set in relation to the FN concentration of plasma
      pools in cats and dogs. A discrimination line of 31.5% completely separated
      malignant from cardiogenic pleural effusions in cats. For the diagnosis of a
      malignant pleural effusion, sensitivity was 100% and specificity was 57%.
      Pleuritis also resulted in high FN concentrations. The FN concentration in
      malignant pleural effusions in dogs differed significantly (P < .02) from that in
      cardiogenic effusions. There were no clinically useful differences in the FN
      concentration in peritoneal effusions in cats and dogs. The FN/albumin ratio was
      significantly higher (P < .02) in dogs with neoplastic abdominal effusion than in
      those with congestive heart failure.

PMID- 8884720
TI  - Magnetic motor evoked potentials in ponies.
AB  - Magnetic stimulation of motor pathways was used to effect motor unit action
      potential recordings from forelimb and hindlimb muscles in unanesthetized ponies.
      Motor pathway conduction velocities to the forelimb and hindlimb were determined
      to be 53.8 +/- 9.6 m/s-1 and 63.4 +/- 8.3 m/s-1, respectively. This noninvasive
      technique will enable more precise evaluation of motor deficits in clinical
      patients than is possible with the neurological examination.

PMID- 8884721
TI  - Thrombosis of the brachial artery in a foal.

PMID- 8884722
TI  - Long-term survival after total gastrectomy for gastric adenocarcinoma in a dog.

PMID- 8884723
TI  - Treatment of renal aspergillosis in a dog using nephrostomy tubes.

PMID- 8884724
TI  - Detrusor-striated sphincter dyssynergia in a dog.

PMID- 8884725
TI  - Management of anterior cruciate ligament injuries in skeletally immature
      adolescents.
AB  - Anterior cruciate ligament (ACL) injuries in skeletally immature adolescents are
      being diagnosed and reported with increasing frequency. Nonoperative management
      of mid-substance ACL injuries in adolescent athletes frequently results in a high
      incidence of giving-way episodes, recurrent meniscal tears, and early onset of
      osteoarthritis. An intraarticular ACL reconstruction (using the central 10-mm
      patellar tendon graft) in young athletes approaching skeletal maturity provides
      predictable excellent knee stability, and the athletes are able to return to
      competitive sports with a decreased risk of recurrent meniscal and/or chondral
      injury. Guidelines for the management of ACL injuries in skeletally immature
      adolescents are presented.

PMID- 8884726
TI  - Radiological method for preoperative determination of isometric attachment points
      of an anterior cruciate ligament graft.
AB  - The purpose of this study was to develop a radiological method which would be
      preoperatively available to help determine the best graft placement (with respect
      to isometricity as well as absence of graft impingement) for all knees. The
      radiological method is described in full detail. We also present the most
      significant experimental work supporting our development. Firstly, we studied the
      path followed by radio-opaque objects inserted in the mobile tibia around the
      fixed femur. Secondly, we compared the distances measured between selected
      femoral and tibial points radiologically (according to our method) and clinically
      (with a currently available isometer). The main results were: (1) every tibial
      point considered moves on an arc of a circle centered or a corresponding femoral
      point. We should then speak of pairs of isometric points instead of a single
      femoral isometric zone; (2) the more posterior the tibial point, the more
      anterior and distal the corresponding femoral point and vice versa; (3) the
      distance variations induced by rotation did not exceed 1.5 to 2.5 mm when
      measured either radiologically or clinically; (4) on the radiological and
      clinical measurements, the difference of length variations during flexion was
      also very small (mean 0.22 mm; SD 1.2 mm). We conclude that this very simple
      method allows us to find the femoral transition line for every knee (whatever its
      size, shape or dynamics). It aids preoperative planning in anterior cruciate
      ligament graft reconstruction.

PMID- 8884727
TI  - Behavior of sutures used in anterior cruciate ligament reconstructive surgery.
AB  - This study was performed to determine the material properties of sutures commonly
      used in orthopedic surgery in order to allow selection of the most appropriate
      one for securing a hamstring or quadriceps tendon graft in anterior cruciate
      ligament (ACL) reconstruction. Three suture materials (number 5 Ticron, number 5
      Ethibond, and 5 mm Mersilene tape) were tested. The ultimate tensile load (UTL)
      with and without a knot, modulus of elasticity, effect of conditioning on the
      behavior of the suture, and plastic deformation were determined for each suture.
      Prior conditioning significantly improved the plastic deformation characteristics
      of all three sutures. Mersilene possessed the highest UTL both with and without
      knots, and its plastic deformation was significantly lower than that of Ticron or
      Ethibond. We feel that these characteristics make it the best suture for use in
      securing hamstring or tendon grafts in ACL surgery. Because of the high UTL
      achieved by Mersilene tape in the knotted surgical loop construct (nearly 500 N),
      it may be possible to achieve fixation integrity approaching that of interference
      fixation with bone blocks.

PMID- 8884728
TI  - Isolated popliteus muscle rupture in polo players.
AB  - Isolated rupture of the popliteus muscle seems to be extremely rare, with only
      two cases described in the English literature. We present two cases of magnetic
      resonance imaging-verified isolated rupture of the popliteus muscle in polo
      players with the same injury mechanism-external rotation trauma on a flexed knee.
      Functional testing of the popliteus muscle in the figure of four position was
      positive in both cases. Full recovery was observed after 6 weeks of
      physiotherapy.

PMID- 8884729
TI  - Elevation of the tibial tubercle for patellofemoral pain syndrome. An 8- to 15
      year follow-up.
AB  - One hundred patients were operated on by the Maquet procedure for chondromalacia
      patellae. All of them were first re-examined after a mean follow-up of 4 years,
      and 65 of them re-examined after a mean follow-up of 11 years (range, 8-15
      years). The pain score improved significantly after the operation and remained
      unchanged with longer follow-up. The success rate was only 62% at both follow
      ups. Outerbridge grade IV chondral lesions at the time of surgery were associated
      with a significant improvement of the pain score at the 4-year follow-up and a
      success rate of 69%. The Maquet procedure should only be proposed for chronic
      retropatellar pain with grade IV chondral lesions, after conservative treatment
      has proven unsuccessful, as the expected failure rate is about 30%.

PMID- 8884730
TI  - A ganglion of the anterior horn of the medial meniscus invading the infrapatellar
      fat pad. Case report.
AB  - A case of ganglion of the medial meniscus that had invaded the infrapatellar fat
      pad is presented. Review of the literature embraces theories of pathogenesis, the
      effect on the surrounding tissue, the radiological techniques and the therapy.

PMID- 8884731
TI  - Quadriceps tendon and patellar ligament: cryosectional anatomy and structural
      properties in young adults.
AB  - Structural tensile properties analyses of 10-mm-wide central sections of
      quadriceps tendon-bone (QT-B) and bone-patellar ligament (B-PL) complexes from
      young male donors (mean age 24.9 years, range 19-32 years) were complemented by a
      cryosectional analysis: each QT-B complex was composed of the segment of the
      quadriceps tendon with the proximal half of the patella attached, each B-PL
      complex was composed of the distal half of the patella with the patellar ligament
      attached. A servohydraulic materials testing machine was used to assess ultimate
      failure load of 16 unconditioned and 16 preconditioned QT-B and B-PL complexes at
      an extension rate of 1 mm/s. Ligaments/tendons were preconditioned during 200
      cycles from 50 to 800 N at 0.5 Hz. On cryosections the quadriceps tendons were
      significantly longer and thicker and exhibited a significantly larger bony
      attachment area than the patellar ligaments. Cross-sectional areas of 10-mm-wide,
      full-thickness, central parts of unconditioned quadriceps tendons were
      significantly greater and measured 64.6 +/- 8.4 mm2 with respect to the cross
      sectional area of patellar ligaments, measuring 36.8 +/- 5.7 mm2 (P < 0.0025).
      Ultimate failure loads for unconditioned complexes resulted at 2173 +/- 618 N for
      QT-B complexes and at 1953 +/- 325 N for B-PL complexes (P = 0.43). Ultimate
      failure load values measured 2353 +/- 495 N for preconditioned QT-B complexes and
      2376 +/- 152 N for preconditioned B-PL complexes, respectively (P = 0.77).
      Despite the fact that initial testing length, thickness, cross-sectional shape
      and area of unconditioned QT-B and B-PL complexes were significantly different,
      displacement at ultimate load, energy to failure and total energy were not. In
      terms of ultimate tensile strength, the 10-mm-wide central part of the QT-B
      complex compared favourably to the tensile properties of the human femur-anterior
      cruciate ligament-tibia complex from a comparable young age group. The evidence
      from anatomic, cryosectional and structural properties analyses suggests that the
      QT-B complex may be a valuable and versatile adjunct to the surgeon's
      armamentarium in reconstructive cruciate ligament surgery.

PMID- 8884732
TI  - Occurrence and distribution of free nerve endings in the distal iliotibial tract
      system of the knee.
AB  - Free nerve endings (FNE) are nociceptive sensory elements transmitting
      information on pain and inflammation from the connective tissues to the brain.
      They form an important part of the proprioceptive sensory system of the knee. We
      present a qualitative and quantitative analysis of FNEs in the distal iliotibial
      tract (ITT), documenting their occurrence in this structure as well as their
      specific distribution pattern. FNEs were found in all elements of the distal ITT,
      with their maximum density in the fixation sites of the distal ITT to the femur
      and the tibia. This finding correlates well with anatomical and biomechanical
      studies and stresses the importance of the deep ITT fibre system for lateral knee
      stability. The relative number of FNEs in the distal ITT ranges from 5 to 10 per
      50 mm2 and is comparable to the frequency found in the synovial sheath of the
      cruciate ligaments. These findings have clinical implications for surgical
      procedures on the lateral side of the knee. The distinct anatomy of the distal
      ITT should be respected in all procedures, since extensive operations in this
      area may cause pain and loss of range-of-motion due to alterations of
      proprioceptive function.

PMID- 8884733
TI  - Sports ability after Bankart procedure in professional athletes.
AB  - Recurrent anterior shoulder instability and the restoration of sports ability
      after surgery are common problems, especially among professional athletes. The
      purpose of this study was to evaluate the rate, level and time of returning to
      sports activity activity after Bankart procedure in anterior shoulder instability
      in high level athletes. From 1992-1994 61 patients suffering from recurrent
      anterior shoulder instability were operated on open Bankart procedure, 44 out of
      61 were professional athletes. There were 7 handball, 7 basketball, 6 football, 2
      waterpolo and 1 baseball player and 4 wrestlers, 2 weight-lifters, 2 boxers, 3
      bicyclists, 2 motorists, 2 swimmers, 2 sailors, 2 kayakers and 2 skiers. The mean
      duration of instability was 19.1 months (3-72) before operation. 29 patients had
      posttraumatic recurrent anterior dislocation and 15 patients had posttraumatic
      anterior subluxations. The average number of redislocations was 4.4, ranging from
      2 to 11. At the follow-up examination the patients were tested clinically for
      instability using the special score created by Walch and Duplay and the Constant
      functional score. We measured the strength of the rotator cuff by Kintrex
      isokinetic device from the 10th postoperative week. 35 out of 44 professional
      athletes could be followed-up. The average follow-up period was 14.2 months, from
      6 to 31. 88% of the patients were able to return to sports participation, 66% on
      the previous level and 22% on a lower level. 12% of the patients finished their
      professional sports career. The mean rehabilitation period was 5.8 months, the
      average period of full restoration of sports ability was 9.3 months. Similar
      results were documented with the Constant score and the Walch-Duplay test (88%
      excellent or good, 12% fair). The main reason for the inability to continue
      sports activity was some pain during extreme abduction and external rotation of
      the arm and recurrent sensations of subluxation (3 cases). Based on the results
      of the follow-up examinations an early diagnosis is paramount followed by timely
      surgical intervention to restore anatomical integrity in proven cases of shoulder
      instability in professional athletes. The open Bankart procedure is preferred
      giving excellent functional results and providing good chances for the athletes
      to return to their previous sports level.

PMID- 8884734
TI  - Knee joint proprioception: a comparison between female intercollegiate gymnasts
      and controls.
AB  - The role of proprioception as a protective mechanism has gained interest in
      recent years. From the clinical standpoint, several studies have dealt with ways
      to enhance proprioception following surgery and during rehabilitation. If
      kinesthesia (ability to detect passive motion) can be enhanced as a consequence
      of long-term athletic training, such training must be included as a part of the
      rehabilitation process to protect the patient from reinjury. Consequently, the
      purpose of this study was to compare the kinesthetic knee pattern between trained
      gymnasts and healthy nongymnasts. The proprioception testing device (PTD) was
      used to evaluate knee kinesthesia. From 45 degrees of flexion, the knee was
      passively extended with the PTD. The device was stopped by the subject when this
      passive motion was detected. Fifteen healthy college-age female gymnasts (mean
      age 19.3 years) and 30 normal volunteers (mean age 20.7 years) comprised our
      study sample. A one-way analysis of variance (ANOVA) was used to compare the mean
      values of the dominant gymnastic knee to the dominant knee in the control group.
      Results revealed statistically significant mean differences between the trained
      gymnastic group and the untrained control group (F1.34(.95) = 7.17, P = 0.011).
      The results of this study suggest that extensive training has a positive
      influence on knee kinesthesia in addition to increasing muscle tone. According to
      the findings of this and other studies, highly trained athletes possess enhanced
      neurosensory pathways which are speculated to develop as a result of long-term
      athletic training. Although definite conclusions cannot be made from our
      investigation, prospective studies can determine the true role of athletic
      training in proprioceptive patterns.

PMID- 8884735
TI  - Endoscopic revision of an infected Syme amputation. Case report and review of the
      literature.
AB  - Arthroscopic revision of intra-articular infection is more and more accepted. To
      our knowledge, there is no description of endoscopic management of an infected
      amputation stump. This paper presents the case of a 54-year-old man after a Syme
      amputation of his left leg because of diabetic gangrene of the foot. A local
      infection of the stump was treated successfully with two endoscopic debridements
      and lavage. Additionally, the patient received local antibiotics by the
      application of antibiotic collagenous fleece and chains. This therapeutic
      management combined with early weight-bearing produced a stable stump.

PMID- 8884736
TI  - Some aspects of the history of membrane-damaging toxins.
AB  - In this review the following topics are considered: (a) the character of
      biomedical research and how it has changed during the last six decades; (b) the
      early history of membrane-damaging toxins; (c) comparative toxinology as
      illustrated by similarity of the toxins of the brown recluse spider and the
      bacterial agent of peudotuberculosis, and by similarity of a toxin of a sea
      anemone and the thiol-activated membrane-damaging agents of bacteria; (d)
      examples of the diversity of membrane-damaging toxins; (e) cooperative or
      synergistic lytic systems; and (f) the outlook for the future.

PMID- 8884737
TI  - Synthesis, maturation and export of the E. coli hemolysin.

PMID- 8884738
TI  - Measles virus hemagglutinin mediates monocyte aggregation and increased adherence
      to measles-infected endothelial cells.
AB  - The effect of measles virus (MV) infection on monocyte adhesion was studied using
      human peripheral blood monocytes and monocytic and endothelial cell lines. The
      infection of monocytic U-937 cells led to the formation of large cellular
      aggregates. Aggregation was independent of intercellular adhesion molecule-1
      (ICAM-1)/lymphocyte function-associated antigen-1 (LFA-1), but could be inhibited
      by monoclonal antibodies (mAb) against the MV hemagglutinin glycoprotein (MV-H).
      mAb against the MV receptor, CD46, also blocked aggregation. No significant
      changes in the cell surface expression of adhesion molecules CD11a, CD11b, CD11c,
      CD18, CD54, CD44, CD49d (alpha 4-integrin) and CD62L (L-selectin) were observed
      on MV-infected monocytes. Infection of a human endothelial cell line, EAhy 926
      (HEC), with MV led to a two-fold increase in 1CAM-1 expression and a two-fold
      increase in monocyte adherence to the HEC (from 22 +/- 1.6% to 42 +/- 4.8%).
      However, ICAM-1 mAb reduced monocyte adhesion to the control and MV-infected HEC
      to a similar degree, whereas anti-MV-H antibodies abolished the difference
      between binding to infected and control HEC. We conclude that MV hemagglutinin
      mediated both the homo typic aggregation in infected monocyte cultures and
      increased monocyte adherence to the infected endothelial cells.

PMID- 8884739
TI  - Sialic acids of both the capsule and the sialylated lipooligosaccharide of
      Neisseria meningitis serogroup B are prerequisites for virulence of meningococci
      in the infant rat.
AB  - We investigated the contribution of the polysialic acid capsule and of terminal
      lipooligosaccharide (LOS) sialylation to the pathogenicity of Neisseria
      meningitidis in vivo using a set of defined isogenic mutants of the N.
      meningitidis strain B 1940 deficient in either capsule synthesis or LOS
      sialylation. Furthermore a spontaneous capsule-deficient variant was
      investigated, which was capable of switching on the capsule synthesis at a
      frequency of 3 x 10(-3) in vitro. Infection of infant rats with the wild-type
      strain revealed a high potential to cause bacteremia. This potential was
      attenuated in the capsule-phase variable mutant (LOS sialylation+). However,
      using a mutant irreversibly deficient in capsule synthesis, but expressing a
      sialylated LOS, bacteremia could only be achieved using 10(6) times higher
      numbers of bacteria when compared to the wild-type. The unencapsulated bacteria
      were located extracellularly upon examination of blood smears, suggesting that
      defense mechanisms, i.e. phagocytosis, directed against unencapsulated
      meningococci were exhausted using very high infecting doses. Interestingly, when
      infant rats were infected with encapsulated meningococci which were unable to
      sialylate the LOS, bacteremia could never be achieved, even with an infective
      dose as high as 10(8) colony forming units (CFU). Despite the presence of
      capsular polysaccharide this mutant was phagocytosed by peritoneal phagocytes, as
      was the unencapsulated, LOS-sialylated mutant, suggesting that the inability to
      cause bacteremia was due to a higher susceptibility to the action of the
      complement system, which is virtually unsaturable. We conclude that in the infant
      rat model of meningococcal infection both forms of sialic acid on the bacterial
      cell surface are indispensable for systemic survival.

PMID- 8884740
TI  - Binding of the V proteins to the nucleocapsid proteins of human parainfluenza
      type 2 virus.
AB  - Interaction of the nucleocapsid (NP) and V proteins of human parainfluenza type 2
      virus (HPIV-2) was investigated using a transient expression system. When the NP
      proteins were co-expressed with the V proteins, some of the NP proteins were
      translocated into the nuclei. These findings suggest that the NP protein interact
      with the V proteins. We examined the interaction of the NP proteins and the P, V
      proteins or deletion mutants of V protein using immunofluorescence and co
      immunoprecipitation plus Western blotting analyses, and showed that the V
      proteins of HPIV-2 bind to the NP proteins and that the N-terminal domain of V
      protein interacts directly with the NP proteins. When the NP proteins were co
      expressed with the V proteins or the N-terminal fragments (aa 1-46), the NP
      proteins were detected diffusely in the nuclei of the transfected cells, and were
      also detected in cytoplasmic inclusions. The NP and V proteins were co-localized
      in the nuclei or cytoplasm. Furthermore, the NP proteins were co-precipitated
      with the P, V, and V (1-164) proteins by a specific antibody. The P proteins
      interact more closely with the NP proteins than do the V proteins. These findings
      indicate that the V proteins have the ability to bind the NP proteins.

PMID- 8884742
TI  - A practical framework for understanding compensatory behaviour in people with
      organic memory impairment.
AB  - This paper describes a framework for understanding compensatory behaviour in
      people with organic memory impairment. It builds on a theoretical framework
      proposed by Backman and Dixon (1992) who distinguish four steps in the evolution
      of compensatory behaviour: (a) origins, (b) mechanisms, (c) forms, and (d)
      consequences. Although this framework is useful in understanding compensation in
      neurologically impaired adults, other factors need to be taken into account.
      Using data from a long-term follow-up study it is shown that age, severity of
      memory impairment, and additional cognitive deficits are important variables in
      predicting independence and use of compensations several years post
      rehabilitation. The paper concludes with a consideration of how the framework
      might be used in future studies.

PMID- 8884741
TI  - High inflammatory activity is associated with an increased amount of IFN-gamma
      transcripts in peripheral blood cells of patients with chronic hepatitis C virus
      infection.
AB  - The mechanisms underlying the chronic hepatic inflammatory process in hepatitis C
      virus (HCV) infection are not well understood. Some models of experimentally
      induced hepatitis point to a role of interferon-gamma (IFN-gamma) secreted by
      liver-infiltrating peripheral blood lymphocytes (PBMC) in mediating
      hepatocellular injury. In the present study, IFN-gamma gene expression was
      analysed in PBMC and in liver biopsy specimens from patients with chronic HCV
      infection using a quantitative reverse transcriptase polymerase chain reaction
      technique. IFN-gamma gene expression by PBMC from HCV-infected patients
      exhibiting elevated serum transaminase activities was found to be increased up to
      ninefold when compared with (1) healthy individuals, (2) HCV-infected patients
      exhibiting normal or only slightly elevated serum enzyme activities, or (3)
      patients with drug-induced elevated serum transaminase activity. A histo
      pathological evaluation of liver biopsy sections revealed further that high IFN
      gamma gene expression by PBMC was associated with a more pronounced degree of
      inflammatory activity. In individual patients, the expression of IFN-gamma by
      PBMC was shown to parallel closely serum transaminase activities during IFN-alpha
      2a therapy. Moreover, liver biopsy material from patients chronically infected
      with HCV contained higher amounts of IFN-gamma transcripts than liver tissue from
      patients with liver disorders unrelated to HCV infection or without any liver
      disease. These data thus demonstrate a close association between the amount of
      IFN-gamma transcripts in PBMC and in liver tissue and the inflammatory activity
      in chronic HCV infection in man.

PMID- 8884743
TI  - Sensitivity to the frequency of parts and kinds: two principles of organisation
      in semantic memory.
AB  - Are subjects sensitive to the frequency of parts of the same whole in the same
      way that they are sensitive to instances of the same category? Subjects read a
      randomised list of words and then estimated how many words on the list had
      belonged to particular groups, e.g. parts of a bird, or kinds of bird. Groups of
      words were either parts of the same whole, e.g. feathers, beak, wing, or members
      of the same category, e.g. robin, sparrow, eagle. Subjects were asked, either,
      "How many parts of a (bird) did you see?" or "How many kinds of (bird) did you
      see?". Half of the subjects expected the frequency estimation task, whereas for
      the other half, who performed a distractor task during encoding, the task was
      unexpected. In Experiment 1 subjects saw either parts of kinds. Sensitivity to
      frequency did not differ for parts and kinds nor as a function of whether the
      frequency estimation test was expected. In Experiment 2 subjects saw both parts
      and kinds belonging to the same superordinates, e.g. parts of birds and kinds of
      birds, and were asked to estimate the frequency of both types of groupings for
      each superordinate. The results were the same as in Experiment 1. In addition,
      subjects were able to separate the frequency of parts and kinds of the same
      superordinate. The results suggest that, in frequency estimation, part-of and
      kind-of associations can function similarly, and that the mechanism responsible
      for frequency estimation is sensitive to the type of association.

PMID- 8884744
TI  - Spatial imagery preserves temporal order.
AB  - Line drawings were presented in either a spatial or a nonspatial format. Subjects
      recalled each of four sets of 24 items in serial order. Amount recalled in the
      correct serial order and sequencing errors were scored. In Experiment 1 items
      appeared either in consecutive locations of a matrix or in one central location.
      Subjects who saw the items in different locations made fewer sequencing errors
      than those who saw each item in a central location, but serial recall levels for
      these two conditions did not differ. When items appeared in nonconsecutive
      locations in Experiment 2, the advantage of the spatial presentation on
      sequencing errors disappeared. Experiment 3 included conditions in which both the
      consecutive and nonconsecutive spatial formats were paired with retrieval cues
      that either did or did not indicate the sequence of locations in which the items
      had appeared. Spatial imagery aided sequencing when, and only when, the order of
      locations in which the stimuli appeared could be reconstructed at retrieval.

PMID- 8884745
TI  - Describing places: what strategies are used?
AB  - Two experiments examined the role of individual differences and of spatial
      organisation of items in the choice of strategy used in describing environments
      from memory. The three environments presented in slides had different spatial
      layouts: a linear order (the river), the complete absence of a linear order (the
      market), and a mixture of the two (the square). Experiment 1 assessed whether two
      groups of subjects who differed for the use of rotation in a mental rotation task
      "Rotators" and "Jumpers"), would also use different strategies (either "Tour" or
      "Jump") in describing an environment. Results showed that spatial organisation
      had a strong effect on the choice of strategy, but individual differences were
      also present. Strategy stability was then examined in Experiment 2 by repeating
      the description three times. The relevant effect of item spatial organisation on
      strategy choice was again found, but limited to "new" material, i.e. to the first
      presentation, while the Tour strategy appeared from trial two. Results are
      interpreted in terms of the role of the cognitive load the material imposes on
      short-term memory, explaining the effect of spatial layout, as well as individual
      differences. This explanation is also compatible with the observed predominance
      of the Tour strategy, especially when material is well known.

PMID- 8884746
TI  - A ROSE is A. Rose is a rose? Exploring the implicit and explicit memorial
      structure of word/name homographs.

PMID- 8884747
TI  - GABAC receptors in the vertebrate retina.
AB  - In the central nervous system (CNS), the inhibitory transmitter GABA interacts
      with three subtypes of GABA receptors, type A, type B, and type C. Historically,
      GABA receptors have been classified as either the inotropic GABAA receptors or
      the metabotropic GABAB receptors. Over the past 10 yr, studies have shown that a
      third class, called the GABAC receptor, also exists. GABAC receptors are found
      primarily in the vertebrate retina and to some extent in other parts of the CNS.
      Although GABAA and GABAC receptors both gate chloride channels, they are
      pharmacologically, molecularly, and functionally distinct. The rho subunit of the
      GABAC receptor, which has about 35% amino acid homology to GABAA receptor
      subunits, was cloned from the retina and, when expressed in Xenopus oocytes, has
      properties similar to retinal GABAC receptors. There are probably distinct roles
      for GABAC receptors in the retina, because they are found on only a subset of
      neurons, whereas GABAA receptors are ubiquitous. This article reviews recent
      electrophysiological and molecular studies that have characterized the unique
      properties of GABAC receptors and describes the roles that these receptors may
      play in visual information processing in the retina.

PMID- 8884748
TI  - Activating mechanism of CNTF and related cytokines.
AB  - Ciliary neurotrophic factor (CNTF) shares structural and functional properties
      with members of the hematopoietic cytokine family. It is composed of a four-helix
      bundle structure and shares the transmembrane signal transducing proteins,
      glycoprotein-130 (gp130) and leukemia inhibitory factor receptor (LIF-R).
      Structure-function analysis showed that the gp130-interactive proteins bind in a
      similar manner to that of growth hormone (site I and II). In addition, gp130
      interactive proteins and granulocyte colony-stimulating factor (G-CSF) utilize
      another binding site (site III) at the boundary between CD loop and helix D. CNTF
      triggers the association of receptor components, resulting in activation of a
      signal transduction cascade mediated by specific intracellular protein tyrosine
      kinases. The Janus kinase (JAK)/signal transducer and activator of transcription
      (STAT) and Ras/mitogen-activated protein kinase (MAPK) signaling pathways have
      been characterized in terms of gp130-interactive protein, and there should be
      other pathways and some crosstalk between them to enhance, prolong, or specify
      the signals.

PMID- 8884749
TI  - Amyloid beta-peptide and oxidative cellular injury in Alzheimer's disease.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder that affects
      primarily learning and memory functions. There is significant neuronal loss and
      impairment of metabolic functioning in the temporal lobe, an area believed to be
      crucial for learning and memory tasks. Aggregated deposits of amyloid beta
      peptide may have a causative role in the development and progression of AD. We
      review the cellular actions of A beta and how they can contribute to the
      cytotoxicity observed in AD. A beta causes plasma membrane lipid peroxidation,
      impairment of ion-motive ATPases, glutamate uptake, uncoupling of a G-protein
      linked receptor, and generation of reactive oxygen species. These effects
      contribute to the loss of intracellular calcium homeostasis reported in cultured
      neurons. Many cell types other than neurons show alterations in the Alzheimer's
      brain. The effects of A beta on these cell types is also reviewed.

PMID- 8884751
TI  - Sleep EEG analysis by linear prediction: frequency changes of slow-wave activity
      within NREM and REM sleep episodes in healthy men.
AB  - The linear prediction method was applied to obtain a power spectra estimate of
      sleep EEG in 10 healthy young men. In order to analyze frequency changes of the
      slow-wave activity (EEG power in the delta band, 0.05-2.88 Hz), the delta mean
      frequency was computed for each 20-second sleep epoch. A mean delta mean
      frequency was calculated for each sleep stage in each individual. Our
      observations indicate that the delta mean frequency decreases during NREM periods
      and increases mainly at the onset of the REM episodes. This finding, in parallel
      with the detailed analysis of slow-wave power variations, leads to an additional
      description of sleep characteristics during transitions between the NREM-REM
      sleep episodes.

PMID- 8884752
TI  - Benzodiazepine binding inhibitory activity: new supportive findings on its
      presence in psychiatric patients and further biochemical analyses.
AB  - The authors investigated the presence of a serum activity inhibiting the specific
      binding of 3H-flunitrazepam (which labels the central benzodiazepine receptors)
      (BBIA) in patients with different psychiatric disorders and analyzed it by means
      of high performance liquid chromatography (HPLC) analysis. The results showed
      that the lowest activity was present in healthy controls who were not different
      from patients with schizophrenia and obsessive-compulsive disorder. On the
      contrary, the BBIA values of these 3 groups of patients were significantly lower
      than those found in patients with bipolar disorder in various phases (depressive,
      mixed or manic), in unipolar depressives and in patients with panic and
      delusional disorders. The HPLC analysis of the serum extracts revealed the
      presence of 3 peaks of activity which were differently distributed in the
      patients and in the healthy controls, peak 3 being totally absent in the last
      group and mainly represented in bipolar depressives. The GABA ratio values showed
      that peaks 1 and 2 behave as agonists while peak 3 behaves as an inverse agonist.
      The mass fragmentography of the different peaks is in progress.

PMID- 8884753
TI  - The Wisconsin Card Sorting Test (WCST) performance in normal subjects: a twin
      study.
AB  - The aim of this study was to evaluate the WCST, a task linked to the frontal
      (prefrontal) cortex, in normal twins to detect an inherited component of frontal
      lobe function. The WCST scores of 15 monozygotic (MZ) twin pairs, 9 dizygotic
      (DZ) twin pairs, and 15 unrelated control pairs were used to compute genetic
      estimates. No significant differences were detected between MZ, DZ and control
      groups intrapair correlation coefficients. No significant heritability estimates
      different by zero were computed. The frontal lobe function measured by WCST
      performance in normal twins does not seem to have a high degree of genetic
      component, and larger samples of twins are required to detect low genetic
      effects. The possible implications of such results about the genetic
      predisposition of frontal deficit in schizophrenia have been discussed.

PMID- 8884754
TI  - Beta-endorphin concentration in peripheral blood mononuclear cells of elderly
      depressed patients--effects of phosphatidylserine therapy.
AB  - beta-Endorphin (beta-EP) concentrations were measured in peripheral blood
      mononuclear cells of 10 elderly women with major depressive disorders, 10 age-
      and sex-matched healthy controls and 10 young healthy controls. beta-EP values
      were measured in resting condition and after stimulation with corticotropin
      releasing hormone (CRH). In patients, beta-EP values were measured in drug-free
      condition and after 30 days of treatment with phosphatidylserine (BCPS), 200
      mg/day, p.o. Basal and CRH-stimulated beta-EP concentrations were the same in
      patients and controls; in patients they did not change after BCPS, in spite of
      significant improvement of the depressive symptomatology.

PMID- 8884750
TI  - Regulation of gap junction coupling in the developing neocortex.
AB  - In the developing mammalian, neocortex gap junctions represent a transient,
      metabolic, and electrical communication system. These gap junctions may play a
      crucial role during the formation and refinement of neocortical synaptic
      circuitries. This article focuses on two major points. First, the influence of
      gap junctions on electrotonic cell properties will be considered. Both the time
      course and the amplitude of synaptic potentials depend, inter alia, on the
      integration capabilities of the postsynaptic neurons. These capabilities are, to
      a considerable extent, determined by the electrotonic characteristics of the
      postsynaptic cell. As a consequence, the efficacy of chemical synaptic inputs may
      be crucially affected by the presence of gap junctions. The second major topic is
      the regulation of gap junctional communication by neurotransmitters via second
      messenger pathways. The monoaminergic neuromodulators dopamine, noradrenaline,
      and serotonin reduce gap junction coupling via activation of two different
      intracellular signaling cascades--the cAMP/protein kinase A pathway and the
      IP3/Ca2+/protein kinase C pathway, respectively. In addition, gap junctional
      communication seems to be modulated by the nitric oxide (NO)/cGMP system. Since
      NO production can be stimulated by glutamate-induced calcium influx, the NO/cGMP
      dependent modulation of gap junctions might represent a functional link between
      developing glutamatergic synaptic transmission and the gap junctional network.
      Thus, it might be of particular importance in view of a role of gap junctions
      during the process of circuit formation.

PMID- 8884755
TI  - Effects of carbamazepine and sodium valproate on 5-HT-induced calcium increase in
      individual C6 rat glioma cells.
AB  - The effects of drugs for affective disorders on the sustained phase of serotonin
      (5-HT)-induced calcium (Ca2+) response were investigated in single C6BU-1 glioma
      cells with digital imaging microscopy. The sustained phase was significantly
      attenuated by 32 microM carbamazepine and 320 microM sodium valproate as well as
      100 nM clomipramine and verapamil, whose effects we evaluated in our previous
      report. The present findings demonstrate that drugs for affective disorders, in
      their therapeutic concentrations, have common action of inhibiting Ca2+ influx,
      and suggest that the Ca2+ antagonistic effect may play an important role in the
      mechanism of the action sites of the drugs for affective disorders.

PMID- 8884756
TI  - Serum Mg2+ and Ca2+/Mg2+ ratio in major depressive disorder.
AB  - Serum Mg2+ has been implicated in the symptom severity and pathophysiology of
      mood disorders. Furthermore, the recent findings of blunted signalling through
      the G-protein-coupled adenylyl cyclase (AC) pathway in major depressive disorder
      (MDD) and the importance of Mg2+ in G-protein/AC function led us to reexamine in
      a large sample whether serum Mg2+ concentrations were decreased in MDD patients.
      In 145 drug-free MDD patients compared with 2 control groups: (a) patients with
      bipolar disorder (n = 33) and (b) non-mood-disordered patients (n = 47), there
      were no differences in Mg2+ levels or Ca2+/Mg2+ ratios. Neither of these measures
      differed when comparing responders and nonresponders to antidepressant treatment.

PMID- 8884757
TI  - Therapeutic efficacy of vincamine in dementia.
AB  - This trial was performed to investigate the therapeutic efficacy of vincamine in
      the treatment of primary degenerative and vascular dementia. 152 male and female
      patients aged between 50 and 85 years from two psychogeriatric centers and two
      nursing homes were initially included in the trial and screened for eligibility.
      142 patients completed the trial. Clinical diagnosis was established according to
      DSM-III-R criteria. Allocation of the patients to the primary degenerative
      dementia of the Alzheimer type (DAT) group or the multi-infarct dementia (MID)
      group was based on computed tomography scans, electroencephalographic findings
      and the Hachinski Ischemic Score. In a 12-week double-blind treatment either 30
      mg vincamine or placebo was given twice daily. Confirmatory statistics included
      item 2 of the Clinical Global Impression (CGI), the total score of the Sandoz
      Clinical Assessment Geriatric (SCAG) scale, the subscale 'need for help' of the
      nurse's rating of geriatric patients (Beurteilungsskala fur geriatrische
      Patienten; BGP) and the total score of the Short Cognitive Performance Test
      (Syndrom-Kurztest; SKT). In addition, data on tolerance and on therapy response
      were evaluated based on descriptive statistics. The therapeutic efficacy of
      vincamine was clearly demonstrated by confirmatory analysis as the drug was
      statistically significantly superior to placebo in all four target variables. The
      clinical relevance of the outcome was further underlined by the results of the
      responder analysis of the variables SCAG, BGP and SKT. Based on the results of
      this trial, it can be accepted that the therapeutic effect of vincamine is
      superior to placebo in patients with mild to moderate dementia of degenerative
      and vascular etiologies.

PMID- 8884759
TI  - Antidepressant and anxiolytic profiles of E-10-hydroxynortriptyline on
      electrocorticograms of rats.
AB  - Electrocorticograms of rats were recorded after administration of increasing
      doses of the major metabolite of nortriptyline (NT), E-10-hydroxynortriptyline (E
      10-OH-NT). The results were compared with those of NT administration. In visual
      as well as computerized evaluations, E-10-OH-NT demonstrated clear antidepressant
      properties, thus confirming previous experiments in depressed patients. There is
      some evidence that E-10-OH-NT also has an anxiolytic profile. The results with
      the parent drug NT were not so pronounced. Since E-10-OH-NT has been shown to be
      devoid of side effects when previously administered to humans, this substance is
      clearly to be considered of interest for potential development into a new
      antidepressant. Whether or not the anxiolytic profile is of clinical interest
      needs to be investigated further.

PMID- 8884758
TI  - Catecholaminergic, neuroendocrine and anxiety responses to acute psychological
      stress in healthy subjects: influence of alprazolam administration.
AB  - We studied the effect of alprazolam (APZ) in 12 healthy volunteers on the
      psychological stress-induced activation of emotion and on the pituitary-adrenal,
      adrenomedullary and sympathoneuronal systems. After 3 days of placebo or APZ (1
      mg/day orally) administration, we examined plasma levels of adrenocorticotropic
      hormone, cortisol, L-3,4 dihydroxyphenylalanine, dopamine, norepinephrine (NE),
      epinephrine, metanephrine, normetanephrine, homovanillic acid, vanillylmandelic
      acid, 3-methoxy-4-hydroxy phenyglycol, urinary levels of cortisol and
      catecholamines, circulatory responses and state anxiety levels in subjects
      undergoing psychological stress based on viewing horror, violence, danger and war
      film clips. Film viewing produced modest rises of state anxiety levels, of plasma
      NE concentration and of diastolic blood pressure in both the placebo and drug
      groups. APZ significantly reduced anxiety levels at the beginning of the
      experimental session and caused a decrease of noradrenergic and dopaminergic
      neurotransmitter and cortisol concentrations. Our data suggest that APZ reduced
      anxiety related to the expectation of the event, while the circuitry between
      structures responsible for anxiety and peripheral sympathoneural function was
      still found to be partly sensitive to film viewing.

PMID- 8884761
TI  - Dorsal rhizotomy induces transient expression of the highly sialylated isoform of
      the neural cell adhesion molecule in neurons and astrocytes of the adult rat
      spinal cord.
AB  - Expression of the weakly adhesive, highly sialylated isoform of the neural cell
      adhesion molecule is a feature common to cell capable of migration and
      conformation changes. 11,18,19 Polysialylated neural cell adhesion molecule also
      intervenes in axonal outgrowth and synaptogenesis during development and after
      lesion. 11,13 High levels of polysialylated neural cell adhesion molecule
      immunoreactivity are normally visible in laminae I,II and X of the adult rat
      spinal cord. 2,15 We how here that unilateral cervical dorsal rhizotomy induced
      no detectable changes in immunoreactivity in these areas. However, 24 h after
      lesion, polysialylated neural cell adhesion molecule immunoreactivity appeared in
      neurons scattered in laminae III-IX, ipsi-and contralateral to lesion. This
      reaction increased particularly on the contralateral side, became maximal at four
      days and disappeared eight days later. At this time, there was immunolabelling of
      astrocytes with an activated morphology. The astrocytic labelling, predominant on
      the side ipsilateral to the lesion, was strongest 12 days after rhizotomy, then
      diminished progressively. Deafferentation thus causes a transient expression of
      polysialylated neural cell adhesion molecule within areas of the spinal cord
      distinct from those which permanently express this adhesion molecule. Such
      expression occurs both in neurons and glial cells, with a temporal pattern
      specific to each type of cell.

PMID- 8884760
TI  - Effects of alprazolam and bromazepam on visual search and verbal recognition
      memory in humans: a study with event-related brain potentials.
AB  - The effects of two benzodiazepines (alprazolam and bromazepam) on performance and
      event-related brain potentials (ERPs) in visual search and verbal recognition
      memory paradigms were tested in a placebo-controlled double-blind paradigm
      employing 12 young healthy subjects. Both drugs exerted similar effects on
      performance and electrophysiological measures. Reaction times and hit rates were
      adversely affected in both paradigms. The ERP pattern in the visual search
      experiment suggested an impairment in selective attention (reduction of N1
      component) and of automatic feature registration (posterior N2 reduction). In the
      world recognition experiment a dramatic reduction of the N400 component was seen
      under benzodiazepines. This is interpreted as reflecting an impaired ability to
      perform context integration processes.

PMID- 8884762
TI  - Global and serial neurons form A hierarchically arranged interface proposed to
      underlie memory and cognition.
AB  - It is hypothesized that the cholinergic and monoaminergic neurons of the brain
      from a global network. What is meant by a global network is that these neurons
      operate as a unified whole, generating widespread patterns of activity in concert
      with particular electroencephalographic states, moods and cognitive gestalts.
      Apart from cholinergic and monoaminergic global systems, most other mammalian
      neurons relay sensory information about the external and internal milieu to
      serially ordered loci. These "serial" neurons are neurochemically distinct from
      global neurons and commonly use small molecule amino acid neurotransmitters such
      as glutamate or aspartate. Viewing the circuitry of the mammalian brain within
      the global-serial dichotomy leads to a number of novel interpretations and
      predictions. Global systems seem to be capable of transforming incoming sensory
      data into cognitive-related activity patterns. A comparative examination of
      global and serial systems anatomy, development and physiology reveals how global
      systems might turn sensation into mentation. An important step in this process is
      the permanent encoding of memory. Global neurons are particularly plastic, as are
      the neurons receiving global inputs. Global afferents appear to be capable of
      reorganizing synapses on recipient serial cells, thus leading to enhanced
      responding to a signal, in a particular context and state of arousal.

PMID- 8884763
TI  - Glutamate hyperexcitability and seizure-like activity throughout the brain and
      spinal cord upon relief from chronic glutamate receptor blockade in culture.
AB  - Cortical structures such as the hippocampus and cerebral cortex are considered to
      be particularly susceptible to seizure and epileptiform electrical activity and,
      as such, are the focus of intense investigation relative to hyperexcitability. To
      determine whether parallel glutamate-mediated hyperexcitability and seizure-like
      activity in the rat can be generated by neurons irrespective of their origin
      within the CNS, we maintained cells from the spinal cord,hippocampus, olfactory
      bulb, striatum, hypothalamus, and cortex in the long-term presence of glutamate
      receptor antagonists 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2
      3-dione. After removal of chronic (three to 11 weeks) glutamate receptor block,
      whole-cell patch-clamp recordings from current-clamped neurons (n = 94) revealed
      an immediate increase in large excitatory postsynaptic potentials and a
      depolarization of 20-35 mV that was often sustained for recording periods lasting
      5 min (54% of 66 neurons from all six areas). The intense activity was not seen
      in age-matched control neurons not subjected to chronic glutamate receptor block.
      Selective blockade of ionotropic glutamate receptors showed that the
      hyperexcitability was due to an enhanced response through both AMPA/kainate and N
      methyl-D-aspartate receptors. Relief from chronic glutamate receptor block also
      increased inhibitory activity, as revealed by an increase in inhibitory
      postsynaptic currents while neurons were voltage-clamped at -25 mV. These
      inhibitory postsynaptic currents could be blocked with bicuculline, indicating
      that they were mediated by an enhanced GABA release. This enhanced GABA activity
      reduced, but did not eliminate, the glutamate-mediated hyperactivity, shown by an
      increase in both intracellular Ca2+ and excitatory electrical activity when
      bicuculline was added. When the glutamate receptor block was removed, cells (n >
      1000) from all six regions showed exaggerated Ca2+ activity, characterized by
      abnormally high increases in intracellular Ca2+, rising from basal levels of 50
      100 nM up to 150-1600 nM. Cd2+ eliminated the hyperexcitability by blocking Ca2+
      channels, and reducing excitatory transmitter release and response. Fura-2
      digital imaging revealed Ca2+ oscillations with periods ranging from 4 to 60 s.
      Ca2+ peaks in oscillations in oscillations were synchronized among most neurons
      recorded simultaneously. That synchronization was dependent on a mechanism
      involving voltage-dependent Na+ channels was demonstrated with experiments with
      tetrodotoxin that blocked Ca2+ rises and synchronous cellular behavior. Removal
      of the glutamate receptor antagonists resulted in the glutamate-mediated death of
      44% of the cells after 23 days of chronic block and 82% cell death after 40 days
      of chronic block. Nimodipine substantially reduced cell death, indicating that
      one mechanism responsible for the enhanced cell death after relief from chronic
      glutamate receptor block was increased intracellular Ca2+ entry through L-type
      voltage-gated calcium channels. These data indicate that glutamate is released by
      neurons from all areas studied, including the spinal cord. Sufficient amounts of
      glutamate can be released from axon terminals from all areas to cause cell
      hippocampal and cortical neurons, but also by neurons from any of the brain
      regions tested after chronic deprivation of glutamate receptor stimulation during
      development. This hyperexcitability is mediated by glutamatergic mechanisms
      independent of the specific excitatory connections existing in vivo. The
      epileptiform activity of neurons from one region is indistinguishable from that
      of another in culture, underlining the importance of synaptic connections in vivo
      that define the responses characteristic of neurons from different brain regions.

PMID- 8884764
TI  - Kainate induces apoptosis in neurons.
AB  - Growing evidence suggests that non-N-methyl-D-aspartate receptor activation may
      contribute to neuronal death in both acute and chronic neurological diseases. The
      intracellular processes that mediate this form of neuronal death are poorly
      understood. We have previously characterized a model of kainate neurotoxicity
      using cerebellar granule cell neurons in vitro and we sought to determine the
      mechanism of kainate-induced neurons degeneration. We found DNA, and chromatin
      condensation using a fluorescent DNA intercalating dye, in cerebellar granule
      cells following exposure to kainate (100 microM). Aurintricarboxylic acid
      protected cerebellar granule cells from kainate-induced death. While the
      morphological and biochemical features of neuronal death induced by kainate
      resembled low-K(+)-induced apoptosis in cerebellar granule cells; the time
      interval from the institution of the death-promoting condition to neuronal death
      was briefer with kainate and did not require new protein or RNA synthesis. These
      results demonstrate that kainate receptor activation can induce transcription
      independent apoptosis in neurons. This in vitro model should be useful in
      identifying the intracellular pathways that link kainate receptor activation with
      apoptosis.

PMID- 8884765
TI  - The inducible 70,000 molecular/weight heat shock protein is expressed in the
      degenerating dentate hilus and piriform cortex after systemic administration of
      kainic acid in the rat.
AB  - Using both immunohistochemistry and in situ hybridization, we examined the rat
      brain for the expression of the inducible 70,000 mol. wt heat shock protein,
      Hsp70, at 3,6,12 and 24 h after systemic administration of kainic acid. In
      contrast to previous reports, the present study demonstrates that neurons in the
      regions most susceptible to seizure-induced cell death accumulate both Hsp70
      messenger RNA and protein. Neurons in the denate hilus and piriform cortex
      contained Hsp70 messenger RNA at 6 h and protein at 12 h. These neutrons
      contained little or no Hsp70 messenger RNA or protein at 24 h when the majority
      of cells in these area were pyknotic. Injured neurons in areas such as the
      parietal cortex, which are less susceptible to seizure-induced cell death,
      expressed and maintained high levels of Hsp70 messenger RNA and protein at 12 and
      24 h. This work suggest that Hsp70 messenger RNA and protein are rapidly and
      transiently expressed in dying neurons, and contradicts the notion that Hsp70
      only accumulates in injured neurons that survive.

PMID- 8884766
TI  - In vivo elevation of extracellular potassium in the rat amygdala increases
      extracellular glutamate and aspartate and damages neurons.
AB  - It is well known that high potassium (K+) solutions introduced by microdialysis
      into normal brain increase the extracellular concentration of the excitatory
      amino acid glutamate, and in vitro studies suggest that a high exogenously
      applied glutamate concentration can produce excitotoxic neuronal death. However,
      only recently were in vivo studies undertaken to determine whether high-K+
      exposure damages neurons. We implanted microdialysis probes into rat amygdalae
      bilaterally, and after a 2-h baseline period exposed one side to a modified Krebs
      Ringer-bicarbonate solution containing 100 mmol/l KCl for 30,50 and 70 min,
      followed by a 2-h recovery period, and 70 min and 3 h without a recovery period.
      Of 100.9 +/- 2.0 mmol/l KCl, 12.0 +/- 1.0% was extracted by amygdalar tissue in
      vivo. Election of the extracellular K+ concentration in the amygdala for 70 min
      or longer without a recovery period produced extensive neuronal damage and
      edematous-appearing neuropil in the tissue dialysed, as well as loss of normal
      neurons. Histological evidence of edema subsided in the groups with a 2-h
      recovery period. Although the number of damaged neurons was not significantly
      higher in the group with a 70 min high-K+ exposure and 2-h recovery period, the
      number of normal neurons was reduced, suggesting cell loss. During 70-min high-K+
      exposure, the extracellular glutamate concentration increased to 242-377% of
      baseline during the first 60 min, and extracellular aspartate rose to 162-213%
      during the first 50 min; extracellular taurine rose even higher, to 316-567% of
      baseline, and glutamine fell to 14-27% of baseline. Extracellular serine was
      decreased at 20, 50 and 70 min of high-K+ exposure; extracellular glycine was
      unchanged. The elevated extracellular glutamate and aspartate concentrations
      suggest that exposure of the amygdala to high extracellular K+ may produce cell
      death through an excitotoxic process, and point the way to future studies to
      define the specific mechanisms involved.

PMID- 8884767
TI  - Distinct distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      (AMPA) receptor subunits and a related 53,000 M(R) antigen (GR53) in brain
      tissue.
AB  - Polyclonal antibodies against specific carboxy-terminal sequences of known alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits (GluR-4)
      were used to screen regional homogenates and subcellular fractions from rat
      brain. Affinity purified anti-GluR1 (against amino acids 877-899), anti-GluR2/3
      (850-862), and anti-GluR4a and anti-GluR4b (868-881) labeled distinct subunits
      with the expected molecular weight of approximately 105,000. These antigens were
      shown to have distinct distributions in the brain. While GluR2/3 epitopes had a
      distribution profile similar to that of the presynaptic marker synaptophysin,
      GluR1 was notable for its abundance in the hippocampus and its relatively low
      density in neocortical areas, and GluR4 was highly enriched in cerebellar tissue.
      An additional antigen (glutamate receptor-related, GR53) of lower molecular
      weight (50,000-59,000) was recognized in rat, human, frog, chick and goldfish
      brain samples by anti-GluR4a as well as by anti-GluR1 at, an antibody that
      specifically recognizes the extracellular aminoterminal domain of GluR1 (amino
      acids 163-188). Both antibodies also labeled antigens of approximately 105,000
      mol. wt in brain tissue from all species tested. The approximately 53,000 mol. wt
      antigen was concentrated 10-20-fold in synaptic membranes vs homogenates across
      rat brain regions. Both the 105,000 and the 53,000 mol. wt proteins were also
      concentrated in postsynaptic densities, and neither of the two antigens were
      evident in seven non-brain tissue samples. These data indicate that AMPA
      receptors have regionally different subunit combinations and that some AMPA
      receptor composites include proteins other than the conventional 105,000 mol. wt
      GluR subunits.

PMID- 8884768
TI  - Metabotropic glutamate receptor subtype agonists facilitate long-term
      potentiation within a distinct time window in the dentate gyrus in vivo.
AB  - Trans-azetidine-2,4-dicarboxylic acid (ADA) is a putative selective agonist of
      group 1 metabotropic glutamate receptors. It has been shown previously that
      application of ADA prior to a short-term potentiation-inducing high-frequency
      tetanus facilitates long-term potentiation in vivo. In order to examine the role
      of metabotropic glutamate receptors in this response, we studied the effect of
      ADA in the dentate gyrus of the rat when applied after high-frequency tetanus to
      the perforant path. A comparison was made with the effects of the metabotropic
      glutamate receptor group 1 agonist 3,5-dihydroxyphenylglycine. Drugs were applied
      via a cannula implanted in the lateral cerebral ventricle. Both population spike
      amplitude and field excitatory postsynaptic potential were measured. Weak
      tetanization produced a short-term potentiation of field excitatory postsynaptic
      potential and population spike which decayed to baseline values by 90 min, and
      was unaffected by vehicle injections. Application of ADA (20 mM/5 microliters) or
      3,5-dihydroxyphenylglycine (4mM/5 microliters) 5 min after high-frequency tetanus
      facilitated short-term potentiation into a long-term potentiation which lasted
      over 24 h. (R,S)-alpha-Methyl-4-carboxyphenylglycine (200 mM/5 microliters), a
      metabotropic glutamate receptor antagonist, when applied prior to high-frequency
      tetanus and ADA or 3,5-dihydroxyphenylglycine, completely inhibited this effect.
      ADA applied 10,15,20 and 25 min after high-frequency tetanus also facilitated
      short-term potentiation into long-term potentiation, but the magnitude of long
      term potentiation was smaller than than produced by ADA given 5 min after
      tetanus. Similar effects were seen with 3,5-dihydroxyphenylglycine applied 25 min
      after high-frequency tetanus. When (R,S)-alpha-methyl-4-carboxyphenylglycine was
      applied prior to high-frequency tetanus and ADA or 3,5-dihydroxyphenylglycine
      applied 30 min after high-frequency tetanus, or after short-term potentiation
      decay, elicited no facilitation of long-term potentiation. These results indicate
      that a distinct time window for the enhancement by ADA and 3,5
      dihydroxyphenylglycine of short-term potentiation into long-term potentiation
      occurs in the dentate gyrus in vivo. This suggests that metabotropic glutamate
      receptor activation in long-term potentiation occurs within a finite period of
      time and may be mediated by group 1 metabotropic glutamate receptors.
      Furthermore, it suggests that metabotropic glutamate receptor modulation of N
      methyl-D-aspartate receptors does not account for the role of metabotropic
      glutamate receptors in long-term potentiation.

PMID- 8884769
TI  - Similarities in the age-related hippocampal deposition of periodic acid-schiff
      positive granules in the senescence-accelerated mouse P8 and C57BL/6 mouse
      strains.
AB  - With advancing age clusters of abnormal granules positive for periodic acid
      Schiff appear in the hippocampus of C57BL/6 (B6) mice and the senescence
      accelerated mouse (SAM) P8. The granules can also be visualized with a polyclonal
      antibody to a 110,000 mol. wt laminin-binding protein and stain specifically with
      a monoclonal antibody to heparan sulfate proteoglycan. The present study used
      light and electron-microscopic analysis to compare the staining and morphological
      properties of these granules in SAM P8 hippocampus with those in B6 hippocampus
      at different ages. The results of the light-microscopic analysis revealed that
      granules in SAM P8 and B6 had similar morphology, staining characteristics and
      distribution patterns, and appeared to have a close association with astrocytic
      process. The onset of granules in SAM P8 mice (at two to three months of age) was
      earlier than that observed in B6 mice (at four to six months of age), but the
      maximum incidence was similar in both strains. Electron-microscopic analysis
      revealed that the granules in SAM P8 and B6 mice also had a very similar
      ultrastructure. Granules in both strains were surrounded by a discontinuous
      membrane and contained mostly crystalline-like, degenerated material. The
      successive ultrastructural changes from the exterior to interior of the granules
      suggest that the degenerative process was initiated outside the granules and that
      degenerative structures migrate inward. Astrocytes and heparan sulfate
      proteoglycan are closely associated with beta-amyloid deposits in Alzheimer's
      disease. The presence of astrocyte-associated heparan sulfate proteoglycan
      positive material in aged SAM P8 and B6 mice might model age-related alterations
      in glia function possibly involved in human cerebral amyloidogenesis.

PMID- 8884770
TI  - In vitro autoradiography of ionotropic glutamate receptors in hippocampus and
      striatum of aged Long-Evans rats: relationship to spatial learning.
AB  - Using in vitro autoradiography, we investigated [3H] alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionate, [3H]kainate and [3H]N-methyl-D-aspartate binding in
      two forebrain regions, the hippocampus and striatum, of young (four months of
      age) and aged (24-25 months of age) Long-Evans rats that had previously been
      tested for spatial learning ability in the Morris water maze. Although there was
      substantial preservation of binding in the aged rats, reductions in binding were
      present in the aged rats that were specific to ligand and anatomical region. In
      the hippocampus of aged rats, [3H] alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate binding in CA1 and [3H]kainate binding in CA3 were reduced.
      In contrast, N-methyl-D-aspartate binding was not significantly different between
      age groups. There was evidence of sprouting in the dentate gyrus molecular layer
      of aged rats, indicated by changes in the topography of [3H]kainate binding.
      Binding density was analysed with respect to patch/matrix compartmentalization in
      the striatum. The most striking result was a large decrease in N-methyl-D
      aspartate binding in aged rats that was not limited to any dorsal/ventral or
      patch/matrix area of the striatum. Additionally, [3H]kainate binding in striatal
      matrix was modestly reduced in aged rats. Of these age effects, only N-methyl-D
      aspartate binding in the striatum and [3H]kainate binding in the CA3 region of
      the hippocampus were correlated with spatial learning, with lower binding in the
      aged rats associated with better spatial learning ability. Age-related
      alterations in ionotropic glutamate receptors differ with respect to the receptor
      subtype and anatomical region examined. The age effects were not necessarily
      indicative of cognitive decline, as only two age-related binding changes were
      correlated with spatial learning. Interestingly, in these instances, lower
      binding in the aged rats was associated with preserved spatial learning,
      suggesting a compensatory reduction in receptor binding in a subpopulation of
      aged rats.

PMID- 8884771
TI  - Androgens selectively modulate C-fos messenger RNA induction in the rat
      hippocampus following novelty.
AB  - We have previously shown that androgen receptors are found in high concentrations
      in hippocampal CA1 pyramidal cells. To begin to explore the possible roles for
      androgen receptors in this area of the brain, we studied the effects of
      endogenous and exogenous androgen on the behaviourally induced expression of
      cellular immediate early gene messenger RNAs. Adult male Fischer 344 rats were
      either gonadectomized, gonadectomized and given two Silastic capsules of
      dihydrotestosterone propionate at the time of surgery, or left intact. Three
      weeks later, animals were placed into a novel open field for 20 min. This
      behavioural paradigm caused region- and gene-specific increases of c-fos, jun-B,
      c-jun and zif268 messenger RNA in the hippocampus as determined by semi
      quantitative in situ hybridization histochemistry. The removal of circulating
      androgen by gonadectomy potentiated, whereas dihydrotestosterone treatment of
      castrates attenuated, the behaviourally induced expression of c-fos messenger RNA
      in the CA1 region of the hippocampus. No changes in c-fos messenger RNA
      expression were detected in the CA3 or dentate gyrus regions where androgen
      receptor levels are low. Androgen status did not affect either the basal or
      stimulated expression of Jun-B, c-Jun or zif268 messenger RNA in any of the three
      cellular regions of the hippocampus examined. These results implicate androgen
      receptors in modulating the active response of hippocampal neurons to a
      behaviourally relevant stimulus. Since the products of cellular immediate genes
      can function to alter an array of downstream genes, the modulation of these genes
      in the hippocampus by gonadal hormones may have important ramifications for
      hippocampal function.

PMID- 8884772
TI  - Inescapable stress enhances extracellular acetylcholine in the rat hippocampus
      and prefrontal cortex but not the nucleus accumbens or amygdala.
AB  - A number of experimental results has pointed to a cholinergic involvement in the
      stress response. Recently, analytical techniques have become available to measure
      acetylcholine release in vivo during exposure to various stressors. In these
      experiments, microdialysis was used to monitor acetylcholine output every 15 min
      in the dorsal hippocampus, amygdala, nucleus accumbens and prefrontal cortex
      before, during and after 1 h of restraint, including a 15-min session of
      intermittent tail-shock (1/min, 1 mA, 1-s duration) in rats. In response to the
      stressful event, acetylcholine release was significantly increased in the
      prefrontal cortex (186%; p < 0.01) and hippocampus (168%; P < 0.01) but not in
      the amygdala or nucleus accumbens. The sole effects observed in the amygdala and
      nucleus accumbens occurred upon release from the restrainer, at which point
      acetylcholine levels were significantly elevated in both areas (amygdala: 150%; P
      < 0.05; nucleus accumbens: 13%; P < 0.05). An enhanced acetylcholine release was
      also evident during this sample period in the hippocampus and prefrontal cortex.
      These data demonstrate an enhancement of cholinergic activity in response to
      stress in two acetylcholine projection systems (hippocampus and prefrontal
      cortex) but not in the intrinsic acetylcholine system of the nucleus accumbens or
      the extrinsic innervation of the amygdala. Moreover, the data showed that relief
      from stress was accompanied by a more ubiquitous acetylcholine response that
      extended to each site tested.

PMID- 8884773
TI  - Bridge grafts of fibroblast growth factor-4-secreting schwannoma cells promote
      functional axonal regeneration in the nigrostriatal pathway of the adult rat.
AB  - Axons damaged in the adult mammalian central nervous system are able to
      regenerate when their inhibitory glial environment is replaced with a more
      permissive substrate. Here, we have used long oblique "bridge" grafts of
      fibroblast growth factor-4-transfected RN-22 schwannoma cells to allow
      mechanically lesioned nigrostriatal axons to regenerate back to their original
      target in the adult rat brain. Regenerated axons were able to leave the bridge
      graft to form terminal arborizations and increase the density of tyrosine
      hydroxylase-immunoreactive fibres within the striatum. Bridge grafting also
      resulted in an increase in the number of neurons within the substantia nigra pars
      compacta taking up the fluorescent retrograde tracer Fluoro-Gold from the
      striatum. Animals which had received RN-22 bridge grafts showed lower rates of
      amphetamine-induced rotation 10 weeks after a mechanical lesion of the
      nigrostriatal tract compared to lesioned controls, the magnitude of the
      behavioural effect being related to the number of regenerated axons, and this
      comparative reduction was reversed by mechanical section of the bridge graft. It
      is concluded that our bridge grafting strategy allowed the partial anatomical and
      functional regeneration of the mechanically lesioned nigrostriatal tract, an
      unmyelinated central axon bundle, and that bridge grafting therefore represents a
      realistic approach to the repair of central nervous system lesions involving axon
      tract damage.

PMID- 8884774
TI  - N-methyl-D-aspartate receptors mediate a slow excitatory postsynaptic potential
      in the rat midbrain dopaminergic neurons.
AB  - Repetitive local application of a short train of stimuli to the rat substantia
      nigra and ventral tegmental area elicited a predominant depolarizing, slow, long
      lasting synaptic response in the dopaminergic cells intracellularly recorded in
      vitro. This slow excitatory postsynaptic potential ranged between 13 and 27 mV at
      holding potentials of about-75 mV and lasted for 0.2-6 s. It was not greatly
      affected by the perfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 microM),
      while it was potentiated in the presence of bicuculline methiodide (30 microM) or
      picrotoxin (50-100 microM) and 2-hydroxysaclofen (100-300 microM). In contrast, a
      substantial component of the slow excitatory postsynaptic potential was
      reversibly depressed, in a concentration-dependent manner, by the application of
      the N-methyl-D-aspartate receptor antagonists D,1-2-amino-5-phosphonovalerate (10
      100 microM). Furthermore, the slow excitatory postsynaptic potential was
      reversibly increased by the superfusion of nominally magnesium-free solution. It
      was graded, increasing in amplitude with increased stimulus intensity, and was
      blocked by tetrodotoxin (0.5 microM). We suggest that a sustained activation of
      synaptic terminals containing excitatory amino acids mediates a slow excitatory
      postsynaptic potential in the dopaminergic cells of the midbrain. N-Methyl-D
      aspartate receptors participate in the generation of this slow potential, while
      the alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate/kainate receptors do
      not seem to contribute substantially to this potential. This N-methyl-D-aspartate
      mediated synaptic event could be implicated in the release of dopamine as well as
      in the excitotoxic injury of the dopaminergic neurons.

PMID- 8884775
TI  - Modulation of neurotransmitter release by cholecystokinin in the neostriatum and
      substantia nigra of the rat: regional and receptor specificity.
AB  - The effect of cholecystokinin peptides on the release of dynorphin B, aspartate,
      glutamate, dopamine and GABA in the neostriatum and substantia nigra of the rat
      was investigated using in vivo microdialysis. Sulphated cholecystokinin-8S in the
      dialysis perfusate (1-100 microM) induced a concentration-dependent increase in
      extracellular dynorphin B and aspartate levels, both in the neostriatum and
      substantia nigra. Striatal dopamine levels were only increased by 100 microM of
      cholecystokinin-8S, while in the substantia nigra they were increased by 10-100
      microM of cholecystokinin-8S. Extracellular GABA and glutamate levels were
      increased following 100 microM of cholecystokinin-8S only. Striatal
      cholecystokinin-8S administration also produced a significant increase in nigral
      dynorphin B levels. Local cholecystokinin-4 (100 microM) produced a moderate, but
      significant, increase of extracellular dynorphin B and aspartate levels in the
      neostriatum and substantia nigra. No effect was observed on the other
      neurotransmitters investigated. A 6-hydroxydopamine lesion of the nigrostriatal
      dopamine pathway did not affect the increases in dynorphin B and aspartate levels
      produced by local administration of cholecystokinin-8S. Basal extracellular GABA
      levels were increased significantly in both the neostriatum and substantia nigra
      ipsilateral to the lesion. Nigral glutamate and aspartate levels were also
      increased in the lesioned substantia nigra, but in the lesioned neostriatum
      aspartate levels were decreased. The cholecystokinin-B antagonist L-365,260 (20
      mg/kg, s.c.), but not the cholecystokinin-A antagonist L-364,718 (devazepide; 20
      mg/kg, s.c.), significantly inhibited the effect of cholecystokinin-8S on
      striatal dynorphin B and aspartate levels. In the substantia nigra, however, the
      effect of cholecystokinin-8S on dynorphin B and aspartate levels was inhibited to
      a similar extent by both L-365,260 and L-364,718. Pretreatment with L-364,718,
      but not with L-365.260, prevented the increase in nigral dopamine levels produced
      by nigral cholecystokinin-8S administration. Taken together, these results
      suggest that cholecystokinin-8S modulates dynorphin B and aspartate release in
      the neostriatum and substantia nigra of the rat via different receptor
      mechanisms. In the neostriatum, the effect of cholecystokinin-8S on dynorphin B
      and aspartate release is mediated via the cholecystokinin-B receptor subtype,
      while in the substantia nigra, cholecystokinin-8S modulates dynorphin B and
      aspartate release via both cholecystokinin-A and cholecystokinin-B receptor
      subtypes. Cholecystokinin-8S modulates dopamine release mainly in the substantia
      nigra, via the cholecystokinin-A receptor subtype.

PMID- 8884776
TI  - Morphologically distinct subpopulations of neurotensin-immunoreactive striatal
      neurons observed in rat following dopamine depletions and D2 receptor blockade
      project to the globus pallidus.
AB  - It has been reported in previous studies that perikaryal neurotensin
      immunoreactivity is largely absent in the rat striatum except following striatal
      dopamine depletion or blockade of dopamine D2 receptors, after which, however,
      neurotensin immunoreactivity is elicited in at least two distinct subpopulations
      of striatal neurons [Zahm D.S. (1992) Neuroscience 46, 335-350]. One
      subpopulation of such cells (type I), prominent following D2 receptor blockade,
      is located mainly in the matrix compartment in the rostral, dorsomedial and
      ventrolateral parts of the striatum, and comprises neurons at the large end of
      the medium-sized spectrum that exhibit intense neurotensin immunoreactivity in
      perikarya and proximal dendrites, but rarely display Fos immunoreactivity [Senger
      B. et al. (1993) Neuroscience 57, 649-660]. A second subpopulation (type II)
      resides predominantly in the patch (striosome) and matrix compartments in the
      dorsolateral quadrant of the striatum, and is prominent following administration
      of reserpine. These neurons are at the small end of the medium size range and
      exhibit very light neurotensin immunoreactivity, with little staining of
      dendrites. Fos immunoreactivity is frequently co-localized in striatal neurons
      that exhibit a type II striatal neurotensin response [Brog J.S. and Zahm D.S.
      (1995) Neuroscience 65, 71-86]. In the current study, neurotensin
      immunoreactivity was elicited in striatal neurons by ventral mesencephalic 6
      hydroxydopamine lesions or administration of reserpine or haloperidol.
      Irrespective of which drug was given, retrogradely transported Fluoro-Gold was
      prominently co-localized with neurotensin-like immunofluorescence in the
      perikarya of striatal neurons following injections of the retrograde tracer into
      the globus pallidus. Few double-labeled neurons were observed following
      administration of any of these drugs and injections of Fluoro-Gold into the
      substantia nigra. It is concluded that two subpopulations of neurotensin
      immunoreactive striatal neurons project predominantly to the globus pallidus and
      minimally to the substantia nigra.

PMID- 8884777
TI  - D1 dopamine receptor-deficient mouse: cocaine-induced regulation of immediate
      early gene and substance P expression in the striatum.
AB  - Psychomotor stimulants such as cocaine alter gene expression in neurons of the
      striatum. Whereas many of these effects are mediated by D1 dopamine receptors,
      the involvement of other dopamine receptor subtypes or neurotransmitters is
      likely. To distinguish between these possibilities, regulation by cocaine of
      immediate-early genes and genes encoding neuropeptides was analysed in mice that
      lack functional D1 receptors. Gene expression was examined with in situ
      hybridization histochemistry. In these animals, cocaine failed to induce the
      immediate-early genes c-fos and zif 268. In contrast, substance P expression was
      abnormally increased by this drug. These results demonstrate that some of the
      effects of cocaine on gene regulation are mediated via D1 receptor-dependent
      mechanisms, as evidenced by the absence of immediate-early gene induction in D1
      deficient mice, whereas others also involve additional, non-D1 receptor
      mechanisms, as shown for substance P expression.

PMID- 8884778
TI  - Enhanced synthesis of platelet-derived growth factor following injury induced by
      6-hydroxydopamine in rat brain.
AB  - The kinetics of platelet-derived growth factor messenger RNA synthesis in the
      substantia nigra and in the striatum, before and after unilateral intranigral 6
      hydroxydopamine injection, was studied and compared with that after sham
      operation by a quantitative reverse transcription-polymerase chain reaction. The
      kinetics of brain-derived neurotrophic factor messenger RNA was studied as a
      comparison. Furthermore, the expression of platelet-derived growth factor A- and
      B-chain proteins was analysed by enzyme-linked immunosorbent assay and
      immunohistochemistry. In the ipsilateral striatum of 6-hydroxydopamine-lesioned
      rats, the signal density of messenger RNA for both A- and B-chains had already
      increased at one day and remained at an elevated level during the observation
      period of four weeks. In the substantia nigra ipsilateral to the lesion, a
      strongly increased level of B-chain and, to a lesser extent, of A-chain messenger
      RNA was already detected at 4h, reaching a maximal level at one day. No
      significant increase was seen either in sham-operated rats or in the
      contralateral striatum and substantia nigra. Amounts of platelet-derived growth
      factor proteins were examined separately by enzyme-linked immunosorbent assay in
      both sides of the substantia nigra, striatum and cortex. Three days after 6
      hydroxydopamine lesions the levels of both platelet-derived growth factor A- and
      B-chains increased in the ipsilateral striatum, substantia nigra, and cortex. An
      increase in the A-chain was also observed in the contralateral side of the brain.
      The signal for brain-derived neurotrophic factor messenger RNA increased in the
      striatum in the lesioned side and, to a lesser extent, in the contralateral side,
      as well as in the substantia nigra, where a significant difference was observed
      when compared with the contralateral side. Semiquantitative immunohistochemical
      analysis on the substantia nigra confirmed the enhanced platelet-derived growth
      factor expression, revealing that the majority of the platelet-derived growth
      factor-producing cells were neurons. In summary, we have shown that platelet
      derived growth factor messenger RNA as well as its protein are induced after
      injury to dopaminergic cells. These data indicate an important role of platelet
      derived growth factor in the dopaminergic system.

PMID- 8884779
TI  - Noradrenergic potentiation of cerebellar Purkinje cell responses to GABA: cyclic
      AMP as intracellular intermediary.
AB  - Norepinephrine and the beta-adrenergic receptor agonist, isoproterenol, have been
      shown to potentiate the amplitude of GABAA receptor-mediated whole-cell current
      responses in Purkinje cells acutely dissociated from the rat cerebellum. However,
      the steps leading from the activation of beta-adrenergic receptors to the
      modulation of GABAA receptor remain to be delineated. This study tested the
      hypothesis that a sequelae of intracellular intermediaries involving the cyclic
      AMP second messenger system serves as the subcellular link to promote this
      heteroreceptor interaction. Exposure to cholera toxin, but not to pertussis
      toxin, increased the amplitude of GABA-activated current responses in acutely
      dissociated Purkinje cells. Intracellular dialysis with guanosine 5'-O-(3
      thiotriphosphate) also resulted in a time- and dose-dependent augmentation of the
      response to GABA. while guanosine 5'-O-(2-thiodiphosphate) blocked the
      norepinephrine-mediated facilitation. A positive modulation of the current
      response to GABA was observed following intracellular delivery of cyclic AMP or
      the catalytic subunit of the cyclic AMP-dependent protein kinase. Furthermore,
      the norepinephrine-induced potentiation of the GABA-activated current response
      was prevented in the presence of the Rp isomer of cyclic AMP, the regulatory
      subunit of cyclic AMP-dependent protein kinase and an inhibitor of cyclic AMP
      dependent protein kinase. These findings led to the formulation of a working
      model in which activation of the beta-adrenergic receptor triggers a Gs-protein
      mediated transduction cascade in cerebellar Purkinje cells which activates
      adenylate cyclase, resulting in a rise in intracellular levels of cyclic AMP,
      increased phosphorylating activity by cyclic AMP-dependent protein kinase and,
      ultimately, a potentiation of GABAA receptor function.

PMID- 8884780
TI  - Increased level of neurokinin-1 tachykinin receptor gene expression during early
      postnatal development of rat brain.
AB  - Substance P is known to elicit diverse actions via activating multiple subtypes
      of tachykinin receptors, and these actions appear to be involved not only in
      synaptic transmission but also in synaptic plasticity during development of the
      mammalian central nervous system. The availability of sensitive quantitation of
      individual tachykinin receptor subtypes is crucial for elucidating the
      physiological function specifically mediated by activation of a particular
      receptor subtype. We thus attempted to develop an assay to determine the level of
      messenger RNA molecule encoding the neurokinin-1-type tachykinin receptor and
      apply it for assessment of developmental changes in the neurokinin-1 receptor
      gene expression in the rat brain to explore the role of tachykinin receptors
      during ontogeny. The assay was designed to use a competitive reverse
      transcription-polymerase chain reaction co-amplifying endogenous neurokinin-1
      receptor messenger RNA and internal standard, which enabled specific
      quantification of the number of neurokinin-1 receptor transcripts, ranging from
      3.1 x 10(3) to 1.3 x 10(5) molecules/microgram total RNA. The levels of
      neurokinin-1 receptor gene expression were examined in three different brain
      regions of the rat aged 0-56 days after birth. The order of neurokinin-1 receptor
      messenger RNA expression was hippocampus > cerebral cortex > > cerebellum at all
      ages examined except postnatal day 0, where its expression was more abundant in
      the cerebral cortex than in the hippocampus. From postnatal day 3 onward, the
      hippocampus contained 140-160% of the cortical levels. Although the tachykinin
      receptor expression in the cerebellum was too low to be accurately assessed by
      conventional techniques, our assay enabled us to determine the amount of
      cerebellar neurokinin-1 receptor messenger RNA that changed in the range 7-23% of
      the cortical level during postnatal development. A prominent feature revealed by
      this assay is that the neurokinin-1 receptor gene expression in the rat brain is
      developmentally regulated. The hippocampus displayed a transient peak of
      neurokinin-1 receptor messenger RNA at postnatal day 3 and a subsequent gradual
      decrease. In the cerebral cortex, the amount of the message was highest at birth,
      and was followed by a moderate decrease during postnatal development. At 56 days
      after birth, the expression levels in both brain regions were down-regulated to
      approximately 50% of their maximal levels. The transitory pattern of gene
      expression was also observed in the cerebellum. The results of this study
      demonstrate that the reverse transcription-polymerase chain reaction-based assay
      is useful to quantitate precisely the neurokinin-1 tachykinin receptor message in
      limited tissue samples derived from discrete brain regions. Together with
      previous findings, the increased level of neurokinin-1 receptor messenger RNA
      expression in immature rat brain shown by the present analysis suggests that the
      neurokinin-1-type tachykinin receptor may play a role in the synaptic plasticity
      associated with morphological and functional development of the mammalian CNS.

PMID- 8884781
TI  - Endogenous opioid-mediated inhibition of putative pain-modulating neurons in rat
      rostral ventromedial medulla.
AB  - The rostral ventromedial medulla is a critical relay for midbrain regions,
      including the periaqueductal gray and nucleus cuneiformis, that control
      nociception at the spinal cord. Opioid-containing neurons and terminals are
      concentrated in both the periaqueductal gray and the rostral ventromedial medulla
      in the rat. However, the function of endogenous opioid peptides within the
      medulla in pain modulation is unclear. In this study, bicuculline (30-50 ng) or
      morphine (5 micrograms) microinjected into the periaqueductal gray inhibited the
      tail-flick reflex and the firing of on-cells (cells that increase firing just
      before tail flick) in the medulla. Iontophoretically applied naloxone (20 or 30
      nA), which blocked the inhibition of on-cell firing induced by iontophoresis of
      morphine (20 or 30 nA), consistently reduced the on-cell inhibition produced by
      bicuculline or morphine microinjected into the periaqueductal gray. Naloxone did
      not reduce the inhibition of on-cell firing induced by iontophoretically applied
      clonidine (10 or 20 nA), an alpha 2 adrenoceptor agonist. The firing of off-cells
      (cells that pause in firing just prior to tail-flick) in the medulla was
      increased by bicuculline applied in the periaqueductal gray and was not affected
      by naloxone. The present results suggest that when activation of neurons in the
      periaqueductal gray produces antinociception, endogenous opioid peptides are
      released in the rostral ventromedial medulla and selectively inhibit on-cells,
      which presumably have a facilitating action on spinal nociceptive transmission.
      This action is proposed to be critical for the behavioral antinociception induced
      by bicuculline or morphine in the periaqueductal gray.

PMID- 8884782
TI  - Endogenous opioids acting at a medullary mu-opioid receptor contribute to the
      behavioral antinociception produced by GABA antagonism in the midbrain
      periaqueductal gray.
AB  - This study examined the contribution of endogenous opioids to the antinociception
      produced by microinjection of the GABAA receptor antagonist, bicuculline, into
      the rat midbrain ventrolateral periaqueductal gray region. Microinjection of
      bicuculline (40 ng/0.4 microliter) into the periaqueductal gray produced robust
      antinociception as measured by the tail-flick latency to noxious heat. This
      antinociception was partially reversed by intravenous administration of the non
      selective opioid antagonist naloxone hydrochloride (1 and 5 mg/kg), indicating
      that endogenous opioid release is necessary for this effect. To determine whether
      opioid release in the rostral ventromedial medulla, a major projection target of
      the periaqueductal gray, contributes to this effect, we microinjected another
      opioid antagonist, naltrexone, into the rostral ventromedial medulla. Naltrexone
      in the rostral ventromedial medulla (5 and 10 micrograms/microliter)
      significantly attenuated bicuculline antinociception elicited from the
      periaqueductal gray. Cys2, tyr3, orn5, pen7-amide (26.5 nmol), a selective mu
      opioid receptor antagonist, also reversed the antinociception when microinjected
      into the rostral ventromedial medulla. Microinjections of naltrexone (10
      micrograms/microliter) or cys2, tyr3, orn5, pen7-amide at sites in the medulla
      dorsal to the rostral ventromedial medulla were ineffective. None of the
      antagonists altered baseline tail-flick latencies. These results support the
      hypothesis that a population of periaqueductal gray neurons produces
      antinociception through a mu-opioid receptor-mediated action of endogenous
      opioids in the rostral ventromedial medulla. Thus, two opioid-sensitive pain
      modulating brainstem sites are linked by an endogenous opioid synapse in the
      rostral ventromedial medulla.

PMID- 8884783
TI  - Differential c-fos expression in the nucleus of the solitary tract and spinal
      cord following noxious gastric distention in the rat.
AB  - c-Fos has been used as a marker for activity in the spinal cord following noxious
      somatic or visceral stimulation. Although the viscera receive dual afferent
      innervation, distention of hollow organs (i.e. esophagus, stomach, descending
      colon and rectum) induces significantly more c-Fos in second order neurons in the
      nucleus of the solitary tract and lumbosacral spinal cord, which receive
      parasympathetic afferent input (vagus, pelvic nerves), than the thoracolumbar
      spinal cord, which receives sympathetic afferent input (splanchnic nerves). The
      purpose of this study was to determine the contribution of sympathetic and
      parasympathetic afferent input to c-Fos expression in the nucleus of the solitary
      tract and spinal cord, and the influence of supraspinal pathways on Fos induction
      in the thoracolumbar spinal cord. Noxious gastric distention to 80 mmHg (gastric
      distension/80) was produced by repetitive inflation of a chronically implanted
      gastric balloon. Gastric distension/80 induced c-Fos throughout the nucleus of
      the solitary tract, with the densest labeling observed within 300 microns of the
      rostral pole of the area postrema. This area was analysed quantitatively
      following several manipulations. Gastric distension/80 induced a mean of 724 c
      Fos-immunoreactive nuclei per section. Following subdiaphragmatic vagotomy plus
      distention (vagotomy/80), the induction of c-Fos-immunoreactive nuclei was
      reduced to 293 per section, while spinal transection at T2 plus distention
      (spinal transection/80) induced a mean of 581 nuclei per nucleus of the solitary
      tract section. Gastric distension/80 and vagotomy/80 induced minimal c-Fos in the
      T8-T10 spinal cord (50 nuclei/section), but spinal transection/80 induced 200
      nuclei per section. Repetitive bolus injections of norepinephrine produced
      transient pressor responses mimicking the pressor response produced by gastric
      distension/80. This manipulation induced minimal c-Fos in the nucleus of the
      solitary tract and none in the spinal cord. It is concluded that noxious visceral
      input via parasympathetic vagal afferents, and to a lesser extent sympathetic
      afferents and the spinosolitary tract, contribute to gastric distention-induced c
      Fos in the nucleus of the solitary tract. The induction of c-Fos in the nucleus
      of the solitary tract is significantly greater than in the viscerotopic segments
      of the spinal cord, which is partially under tonic descending inhibition, but is
      not subject to modulation by vagal gastric afferents. Distention pressures
      produced by noxious gastric distention are much greater than those produced
      during feeding, suggesting that c-Fos induction in the nucleus of the solitary
      tract to noxious distention is not associated with physiological mechanisms of
      feeding and satiety. The large vagal nerve-mediated induction of c-Fos in the
      nucleus of the solitary tract following gastric distension suggests that
      parasympathetic afferents contribute to the processing of noxious visceral
      stimuli, perhaps by contributing to the affective-emotional component of visceral
      pain.

PMID- 8884784
TI  - Odor coding properties of frog olfactory cortical neurons.
AB  - Until now, in amphibians, response odor properties of primary cortical neurons
      had never been investigated. Furthermore, very few data on this subject are
      available in other species. This prompted us to explore the functional properties
      of olfactory cortical neurons at rest and in response to odors. To achieve this,
      our experience with odor coding in the first two stages of the frog olfactory
      system, the olfactory mucosa and the olfactory bulb, led us to use odor stimuli
      which were chemical compounds with known stimulating properties, delivered to the
      mucosa in controlled conditions over a wide concentration range. Most of the
      cortical neurons were found to be very silent at rest, their average spontaneous
      activity being significantly lower than that of bulb neurons recorded previously
      in the same conditions. Cortical cells displayed, with all odors combined, 35%
      excitatory responses and 8% inhibitory responses. The excitatory response rate
      was similar to that of the bulb, while the inhibitory response rate was about 4.5
      fold lower. Interestingly, two functional groups of cortical cells emerged based
      both on differences in response temporal patterning to odors delivered at
      increasing concentrations and in qualitative discrimination power. Regarding
      intensity coding, group 1 cells (53%) displayed "classical" temporal pattern
      evolution, increase of discharge frequencies and decrease of latency and burst
      duration, over the concentration range. The responses of group 2 cells (47%) were
      clearly original, since they consisted of a single spike (or more rarely two
      spikes) occurring with a strictly reproducible latency at a given concentration
      and a decreased latency as a function of increasing concentration. The dynamics
      of cell recruitment in the cortex showed that group 1 cell recruitment mimicked
      that of mitral cells, group 2 cells being recruited at higher concentrations. The
      analysis of qualitative discrimination properties of cortical cells regarding the
      eight-odor set revealed that the discrimination power of group 2 cells was
      similar to that of mitral cells. By contrast, the qualitative discrimination
      power of group 1 cells was found to be similar to that of neuroreceptor cells. In
      conclusion, this pioneer approach leads us to report that olfactory cortical
      neurons of the frog are responsive to odors and can be clearly divided into two
      groups based on functional criteria. Group 1 cells, which were relatively
      selective, poorly discriminating but sensitive, may be mainly devoted to
      intensity coding. By contrast, group 2 cells, which were not very sensitive but
      were selective and discriminating, were hypothesized to provide minimal intensity
      coding and thus to be mainly devoted to qualitative discrimination tasks.

PMID- 8884785
TI  - Immunohistochemical mapping of brain triiodothyronine reveals prominent
      localization in central noradrenergic systems.
AB  - Many lines of evidence support a close association between thyroid hormones and
      noradrenergic systems in peripheral tissues. However, there is little certainty
      regarding interactions of the two systems in brain. We now report that
      triiodothyronine is concentrated in both nuclei and projection sites of central
      noradrenergic systems. Immunohistochemical mapping of the hormone revealed the
      following: (1) Locus coeruleus and all other noradrenergic cell groups identified
      were the most prominently labeled neural centers in the brain. (2) The hormone
      was also concentrated in the widely dispersed targets of noradrenergic
      projections. (3) Triiodothyronine labeling in noradrenergic target cells was most
      prominent over the cell nuclei, indicating that the hormone was bound to its
      receptors. Therefore, targets of noradrenergic innervation should be responsive
      to triiodothyronine. (4) Unlike that in noradrenergic target cells,
      triiodothyronine staining was decidedly perikaryal in locus coeruleus (A-6) and
      the other A-1 to A-7 cell groups; the staining pattern in locus coeruleus cytosol
      and processes was heavy, clumped and similar to that seen in contiguous sections
      immunostained for tyrosine hydroxylase. Results of radio-immunoassay,
      immunoabsorption and pharmacological tests demonstrated the specificity of the
      antibody for triiodothyronine and ruled against cross-reactivity with
      norepinephrine or its metabolites as the basis for the staining reactions.
      Although other possibilities consistent with these new observations are given
      consideration, it appears that the structure and activity of central
      noradrenergic systems may be major determinants of triiodothyronine distribution
      patterns and actions in brain. If the noradrenergic system processes both
      triiodothyronine and norepinephrine and conducts them both to nerve cell groups
      receiving its terminal arborizations, specific postsynaptic receptors would be
      available for transduction of both sets of messages. The evidence provides a
      morphological basis for earlier proposals that triiodothyronine may play a
      neuromodulatory or neurotransmitter role in the adrenergic nervous system.

PMID- 8884786
TI  - The development of diurnal rhythmicity in fetal suprachiasmatic neurons as
      demonstrated by fos immunohistochemistry.
AB  - Using Fos immunohistochemistry as a marker of cellular activity, we have shown
      that neurons in the suprachiasmatic nucleus of fetal sheep are active by 75 days
      gestation. From at least 90 days gestation (term is 146 days), these neurons are
      more active during the day (12.00) than at night (03.00) when pregnant ewes are
      exposed to a 12-h light-dark cycle with lights on at 07.00. The day-night
      difference in Fos immunoreactivity persisted when the lighting schedule was
      extended by 8 h to 03.00, although neurons were now more active at 03.00 than
      they were in fetuses maintained on the normal light-dark cycle. When ewes were
      maintained in constant light from 133 to 138 days, the day-night difference in
      Fos immunoreactivity in the fetal suprachiasmatic nucleus was abolished,
      suggesting that diurnal activity of the fetal suprachiasmatic nucleus is
      maintained by a signal related to the external lighting regime. In a twin
      pregnancy where one fetus was optically enucleated at 100 days gestation, the
      density of Fos-immunoreactive neurons in the suprachiasmatic nucleus during the
      day at 138 days was similar to the unoperated twin. This suggests that the
      effects of dim light in the uterus on the fetal retina do not account for the
      high level of Fos immunoreactivity in the suprachiasmatic nucleus in the daytime.
      We propose that a chemical messenger of maternal origin, possibly melatonin,
      suppresses the activity of fetal suprachiasmatic neurons during the night, and
      that fetal suprachiasmatic neurons have endogenous activity which is expressed
      fully during the daytime.

PMID- 8884787
TI  - Tonic protein kinase C-mediated vasoconstriction is unmasked when nitric oxide
      synthase is inhibited in cerebral microvessels.
AB  - Recent evidence indicates that nitric oxide participates in the modulation of
      vascular tone in a variety of vascular beds, including the parenchymal
      microvasculature of the brain. The present study examined the role of protein
      kinase activity in the induction and maintenance of the contractile response when
      endogenous nitric oxide production is inhibited in parenchymal microvessels of
      the rat hippocampus. Microvessels in in vitro slices of the hippocampus were
      monitored using computer-assisted video microscopy. The effects of inhibitors of
      two kinases, protein kinase C and calcium/calmodulin-dependent protein kinase, on
      the vasoconstrictor response to NG-nitro-L-arginine (L-NNA) were investigated.
      The resting luminal diameter of the microvessels examined in this study ranged
      from 9 to 29 microns. Addition of 100 microM L-NNA to the medium superfusing the
      slice constricted microvessels by 38.8 +/- 0.6%. The addition of protein kinase
      inhibitors reversed this constriction in a dose-dependent manner. H-7 (50
      microM), a relatively non-selective protein kinase C inhibitor, elicited an 81.4
      +/- 10.0% reversal of the L-NNA-induced constriction. Bisindolylmaleimide (5
      microM), a selective protein kinase C inhibitor, reversed the constriction by
      69.1 +/- 13.7%. KN-62, an inhibitor of calcium/calmodulin-dependent protein
      kinase II, elicited a smaller yet statistically significant reversal of 17.1 +/-
      5.1%. Pretreatment with H-7 or bisindolyl-maleimide blocked the LNNA-induced
      constriction entirely, while KN-62 did not significantly inhibit the response.
      These findings indicate that the contractile response observed upon removal of
      endogenous nitric oxidergic vasodilation is mediated by protein kinase activity,
      and the contribution of protein kinase C to this effect is greater than that of
      calcium/calmodulin-dependent protein kinase II. The results suggest that a tonic
      nitric oxidergic influence serves to mask the potential for protein kinase C
      mediated vasoconstriction in cerebral microvessels.

PMID- 8884788
TI  - Skin blood flow disturbances in the contralateral limb in a peripheral
      mononeuropathy in the rat.
AB  - Electrical excitation of nociceptive afferents in an extremity has been
      demonstrated to increase skin blood flow in the contralateral extremity. Hence,
      one would expect that loose sciatic nerve ligation, which induces an experimental
      painful peripheral neuropathy, may also provoke a vasodilator response in the
      contralateral hindpaw. On the non-ligated side, such a response may involve
      inhibited skin vasoconstrictor activity as well as neurogenically mediated active
      vasodilation. We studied skin blood flow changes in the rat hindpaw consequent to
      contralateral loose sciatic nerve ligation. After ligation, we also investigated
      whether blockade of afferent input from the ligated sciatic nerve to the spinal
      cord, by means of lidocaine, overrules the vasodilator response in the non
      ligated paw. On the non-ligated side, we assessed the vasoconstrictor response of
      skin microvessels to cooling of the rat abdomen as a measure of skin
      vasoconstrictor activity in this paw. In order to investigate the involvement of
      sensory and/or non-sensory nerve fibers in the non-ligated sciatic nerve on skin
      blood flow abnormalities in the non-ligated paw, we studied the influence of
      blockade of these fibers through successive capsaicin and lidocaine application.
      We show that loose ligation of the sciatic nerve induces a vasodilator response
      in the contralateral hindpaw, which is completely abolished by blockade of
      afferent input from the ligated sciatic nerve. From day 1 after ligation, skin
      vasoconstrictor activity in the non-ligated paw was reduced, as indicated by an
      impaired vasoconstrictor response to cooling of the rat abdomen. Besides,
      blockade of sensory but not of non-sensory nerve fibers on the non-ligated side
      attenuated the vasodilator response in this paw. The data presented here indicate
      that loose ligation of the rat sciatic nerve induces a vasodilator response in
      the contralateral hindpaw. On the non-ligated side, this vasodilator response may
      involve inhibition of skin vasoconstrictor activity, as well as antidromically
      acting sensory nerve fibers.

PMID- 8884789
TI  - Occupationally acquired HIV in health care workers.

PMID- 8884790
TI  - 6-year impact of hearing impairment on psychosocial and physiologic functioning.

PMID- 8884791
TI  - Medical savings accounts: real patient power.

PMID- 8884792
TI  - A new recommendation for physical activity as a means of health promotion.
AB  - The Centers for Disease Control and Prevention and the American College of Sports
      Medicine have issued a recommendation for physical activity to achieve health
      promotion and disease prevention. The recommendation signals a shift in the
      exercise-fitness paradigm to emphasize the relationship between physical activity
      and health. A distinction is made between scheduled vigorous exercise and
      Intermittent moderate physical activity. Moderate physical activity, which can
      include occupational, household, and recreational activity, is recommended for
      all Americans. Contrary to previous beliefs, one no longer needs to adhere to a
      rigid schedule of vigorous exercise to achieve health benefit. Through the
      promotion of physical activity, primary care practitioners have an opportunity to
      significantly impact the nation's public health. Strategies to help clients
      achieve the desired activity levels are needed. Careful assessments and creative
      strategies will help clients meet the physical activity objective.

PMID- 8884793
TI  - Assessment, etiology, and intervention in obesity in children.
AB  - Obesity is a common nutritional disturbance of children and affects 25% to 30% of
      children and adolescents. This paper examines obesity in childhood, the
      measurement of obesity in children, and the relationship of obesity to coronary
      heart disease risks and discusses weight reduction issues in children. Clinically
      useful definitions of obesity in children have not been established, although the
      body mass index, together with anthropometric measurements, may provide the
      practitioner with useful assessment parameters. Discussions of weight in children
      must acknowledge the nutritional requirements of the normally occurring growth
      process. Because growth (and subsequently weight) varies widely among children
      even of the same age, measurement, classification, and control of weight must
      take into account the growth process and growth requirements. Interventions in
      childhood obesity should be directed toward family involvement in the chosen
      strategy and nutritional prudence coupled with typical activity.

PMID- 8884794
TI  - The management of cholesterol in coronary heart disease risk reduction.
AB  - Coronary heart disease remains the number one cause of death in the American
      population. The Framingham Heart Study and other epidemiologic studies have
      demonstrated a direct relationship between elevated total and low-density
      lipoprotein cholesterol in the development of cardiovascular disease. This
      article focuses on secondary prevention, demonstrating that decreased cholesterol
      has a wide range of benefits in patients with cardiovascular disease. Emphasis is
      placed on the Scandinavian Simvastatin Survival Study which reported a 30%
      reduction of total mortality in a population of 4,444 patients with coronary
      heart disease who were treated with an HMG-CoA reductase inhibitor. The National
      Cholesterol Education Program guidelines for cholesterol risk reduction are
      reviewed. The impact of the health care provider as related to adherence and
      medication is discussed. Outcome issues of cost-effectiveness and resource
      utilization relating to cholesterol reduction are emphasized.

PMID- 8884796
TI  - Second licensure for advanced practice: current status.
AB  - This article provides a through update of second licensure for advanced practice
      nurses. The National Council of State Boards of Nursing (NCSBN) has proposed new
      requirements for legislation and licensure for advanced practice nurses. This
      proposal could have major repercussions for all advanced practice nurses,
      depending on whether the state boards of nursing adopt the council's
      recommendation. A review of the historical aspect and the development of nursing
      licensure is reported. Both the 1992 and 1995 second licensure proposals are
      analyzed. Support for and dissent against the proposals by nursing organizations
      and individuals in the nursing community are included. The current status of the
      proposal for second licensure by the National Council of State Boards of Nursing
      is high-lighted.

PMID- 8884795
TI  - Heart failure secondary to left ventricular systolic dysfunction. Therapeutic
      advances and treatment recommendations.
AB  - Although heart failure secondary to left ventricular systolic dysfunction remains
      a serious disease with high morbidity and mortality, pharmacologic intervention
      has been shown to be associated with improved survival and a decreased number of
      hospitalizations. Primary-care providers must be aware of the potential benefits
      of recent therapeutic advances and current treatment recommendations for patients
      with heart failure to receive optimal care. Important aspects of nonpharmacologic
      care are dietary restrictions, exercise training, and through patient education
      and counseling. Pharmacologic therapy includes diuretics, angiotensin-converting
      enzyme inhibitors (ACE) and other vasodilating agents, and digoxin. ACE
      inhibitors are currently recommended for all patients with left ventricular
      dysfunction in whom use of these agents is not contraindicated. The mortality and
      morbidity from heart failure even with ACE inhibitors remain high, however.
      Promising clinical findings with such investigational agents as vesnarinone and
      pimobendan and the new-generation beta-blocker carvedilol suggest future new
      treatments to further improve the prognosis of these patients.

PMID- 8884797
TI  - Avoiding adverse drug reactions in the elderly patient: issues and strategies.
AB  - Primary care providers are faced with numerous challenges when prescribing drugs
      for elderly patients. Multiple drug use, coexisting illness, and normal
      physiologic changes associated with aging place older persons at increased risk
      for adverse drug reactions (ADRs). Sample selection bias in drug clinical trials
      and inappropriate prescribing of contraindicated drugs contribute to the risk
      profile. Because multiple drug use and ADRs are relatively common in the elderly,
      special caution should be used when prescribing for this population. The primary
      care provider should have a good understanding of the factors that put the
      elderly at increased risk for ADR, the classes of drugs inappropriate for elderly
      patients, the physiologic changes of aging that may produce an altered
      pharmacologic response, and the issues associated with adherence to drug therapy.
      This article identifies factors that contribute to ADRs in the elderly and
      proposes strategies to reduce or avoid risk. Identifying and preventing ADRs in
      older Americans is a Healthy People 2000 health protection goal, perhaps more
      important given projected demographics over the next 20 to 30 years.

PMID- 8884798
TI  - Prophylaxis for severe respiratory syncytial virus disease.

PMID- 8884799
TI  - If you build it, they will come.

PMID- 8884800
TI  - Encourage organ donation to help save lives.

PMID- 8884801
TI  - Surgical management of pancreatic cancer.
AB  - The treatment of patients with pancreatic cancer requires the expertise of
      medical oncologists, radiation oncologists, radiologists, and surgical
      oncologists. The surgeon's role in the management of patients with pancreatic
      cancer extends beyond the performance of surgical resection and bypass procedures
      to include diagnosis, staging (including determination of resectability), and
      therapy (both curative and palliative). If a lesion is deemed resectable, the
      surgeon's goal is to achieve clear pathologic margins in order to optimize the
      patient's chances for cure. The surgeon also plays a key role in the palliation
      of disease in patients with unresectable lesions. Biliary and duodenal bypass,
      endoscopic stenting, laparoscopy, and celiac ganglion injection may be needed to
      maximize a patient's remaining quality of life. In addition, the surgical
      oncologist should be involved in clinical trials testing neoadjuvant or adjuvant
      chemoradiotherapies that may lead to the development of more effective therapies
      for pancreatic cancer.

PMID- 8884802
TI  - Role of radiation therapy in the management of the patient with pancreatic
      cancer.
AB  - Most patients who have pancreatic cancer present with advanced disease that is
      not amenable to surgery. For patients whose disease is amenable to surgery and
      who are managed with surgical resection alone, local recurrence rates are high
      and long-term survival rates are low. The use of radiation therapy to treat
      pancreatic cancer has been studied in various clinical contexts. Preoperative
      radiation therapy for resectable or borderline unresectable disease may benefit
      some patients but is not used routinely. For patients with resected disease, data
      from the Gastrointestinal Tumor Study Group (GITSG) trials support the use of
      adjuvant chemoradiation. For patients with locally unresectable disease, the use
      of radiation therapy plus chemotherapy provides modest benefit, as suggested by
      the clinical trials of the GITSG and other groups. Additional studies employing
      modified radiation therapy techniques and improved chemotherapeutic regimens,
      with enhanced radiosensitization and direct cytotoxicity, are needed to optimize
      treatment regimens for patients with this disease.

PMID- 8884803
TI  - New developments in chemotherapy for patients with advanced pancreatic cancer.
AB  - Alleviation of tumor-related symptoms may be a more appropriate basis for judging
      drug efficacy in pancreatic cancer than is tumor shrinkage. Clinical benefit
      response (CBR), a new way to assess clinical efficacy based on marked, sustained
      improvement in pain intensity, analgesic consumption, and performance status, was
      used to evaluate a new chemotherapeutic agent, gemcitabine (2',2'
      difluorodeoxycytidine [Gemzar]). A phase III study of newly diagnosed pancreatic
      cancer patients treated with either gemcitabine or fluorouracil (5-FU) and a
      phase II trial of gemcitabine in patients whose disease had progressed despite
      prior treatment with 5-FU both demonstrated that a significant number of patients
      achieved a CBR with gemcitabine. Prolonged survival was a secondary benefit
      demonstrated in the phase III trial. In both studies, gemcitabine was well
      tolerated, with a relatively mild toxicity profile. These results suggest that
      gemcitabine may serve as a prototype for the development of more effective
      therapies for pancreatic cancer patients.

PMID- 8884804
TI  - Supportive management of the patient with pancreatic cancer: role of the oncology
      nurse.
AB  - The oncology nurse attends not only to the physiologic needs of the patient with
      pancreatic cancer but also to the educational, economic, logistic, and
      psychosocial factors that impact on quality of care. Managing patient care from
      admission through discharge in today's short hospitalization periods, the
      oncology nurse's vigilant attention to "patient care maps" helps keep the
      multidisciplinary healthcare team on schedule, contain costs, and maximize
      hospital resources. Patient and family education provided by the oncology nurse,
      along with take-home reference materials, facilitates adjustment to the cancer
      diagnosis, encourages patient compliance with treatment procedures and pain
      management, and can cut health-care costs by eliminating unnecessary post
      discharge trips to the doctor's office or emergency room. Oncology nursing
      assists patients with pancreatic cancer along the continuum of care via whatever
      pathway is chosen.

PMID- 8884805
TI  - Supportive nutritional management of the patient with pancreatic cancer.
AB  - Progressive weight loss and nutritional deterioration are commonly found in the
      patient with pancreatic cancer. The combined effects of the central anatomic
      location of the pancreas, endocrine and exocrine hormonal insufficiency, and
      treatment toxicity place patients with pancreatic cancer at high risk for
      developing symptoms that affect their ability to consume and absorb adequate
      calories and protein. The use of standardized nutritional assessment and an
      algorithmic approach for nutritional intervention fosters determination of the
      patient's nutritional risk status early in the course of disease, fosters early
      detection of treatable symptoms that interfere with nutritional
      intake/absorption, and can assess the effect of nutritional interventions.
      Supportive nutritional efforts can decrease complications, shorten hospital
      stays, reduce costs, and improve the patient's sense of well-being.

PMID- 8884806
TI  - Supportive care of the patient with pancreatic cancer: role of the psycho
      oncologist.
AB  - Many people who are diagnosed with pancreatic cancer react with a normal level of
      sadness. In others, however, depression represents a concomitant illness, perhaps
      with a biologic basis. Regardless of their origin, these mood disorders are
      controllable. The role of the psycho-oncologist is to distinguish normal
      emotional reactions to having advanced cancer, in which depressive symptoms
      resolve gradually within a week or two with support from family and friends, from
      symptoms of comorbid psychiatric illness, which warrant more extensive treatment,
      such as a combination of supportive psychotherapy, cognitive-behavioral
      techniques, and psychopharmaceutical agents.

PMID- 8884807
TI  - Supportive care of the patient with pancreatic cancer: the role of the oncology
      social worker.
AB  - The goals of oncology social work are to facilitate patient and family adjustment
      to the diagnosis and treatment of the disease; to promote psychosocial recovery
      and rehabilitation for both patient and family; and to facilitate utilization of
      health-care resources. The first step for the social worker is to develop a plan
      of psychosocial care for the patient and family, based on assessment of their
      physical and psychological functioning and available supportive resources. Social
      workers can help patients and their families overcome barriers to accessing
      services such as arrangements for transportation or the procurement of financial
      assistance. The oncology social worker can also be a valuable resource for
      information about the patient's disease, including explanation of treatment plans
      and pain management options.

PMID- 8884808
TI  - Survivorship and pancreatic cancer: the role of advocacy.
AB  - The past 20 years have witnessed important changes in the manner in which many
      people with cancer are opting to deal with their disease. In the past, patients
      yielded to their physicians' treatment choices and assumed that they would be
      told all they needed to know about their condition. Today, many people with
      cancer are taking more active, assertive roles, demanding second opinions and
      treatment option information, and seeking partnerships with their physicians in
      making decisions and managing their overall health-care programs. This article
      describes the growing cancer survivorship movement, explores the varying levels
      of involvement that people with pancreatic cancer may choose, and highlights
      resources available to help individuals and their families hone their survival
      skills.

PMID- 8884809
TI  - Palliative management of the patient with advanced pancreatic cancer.
AB  - For the patient with advanced pancreatic cancer, curative strategies may not be
      appropriate, and palliative symptom management may be the best approach to
      patient care. Oncologists, who have been trained to concentrate on curing cancer,
      must shift focus when caring for these patients and consider palliative treatment
      strategies. Pancreatic cancer patients are multisymptomatic and may require
      treatment for such conditions as pain, bowel obstruction, anorexia, early
      satiety, cachexia, nausea and vomiting, constipation, diarrhea, ascites, and
      dyspnea, among others. These patients may be most effectively managed in a
      hospice care center, which can provide comprehensive care. Alternatively, new
      programs, such as the Cleveland Clinic Palliative Care Program, provide a unique
      setting for the patient with advanced cancer that integrates the qualities of
      hospice care into the acute medical care system.

PMID- 8884810
TI  - Chaplaincy: a continuum of caring.
AB  - A diagnosis of cancer evokes a patient's ultimate existential and spiritual
      concerns. These concerns can be quite pronounced in the patient with pancreatic
      cancer due to the generally advanced stage of the disease at diagnosis and the
      short life expectancy. The role of the chaplain is to maximize the patient's
      ability to use religious resources as a source of coping with pain and suffering
      throughout the course of the disease and its treatment. When a patient enters the
      health-care setting, the chaplain can perform a spiritual assessment and identify
      patients at "high risk" as a result of a disturbance in the functioning of their
      belief system. The chaplain can assist these patients by offering alternatives to
      beliefs that cause suffering and strengthening beliefs that ward off distress.
      Chaplains also minister to the needs of the patient's family and members of the
      medical center. Ritual and discussions about hope or suffering apply equally to
      staff, patients, and patients' families.

PMID- 8884811
TI  - Modulation of 5-fluorouracil resistance in human colon tumor cell lines by
      azidothymidine.
AB  - 5-fluorouracil (5-FU), an inhibitor of thymidylate synthase (EC 2.1.1.45), is
      clinically used in the treatment of several solid tumors, including colorectal,
      head and neck, gastric, and pancreatic cancer. The drug effectively inhibits
      deoxynucleoside triphosphate de novo synthesis. However, this inhibition can be
      circumvented by increased thymidine kinase (EC 2.7.1.21) activity. In the present
      study we examined the effects of 5-FU combined with azidothymidine (AZT), a
      competitive inhibitor of thymidine kinase in human colon tumor cells in vitro,
      including three 5-FU resistant cell lines. The cells were simultaneously
      incubated with various concentrations of 5-FU (0.015 to 150 microM) and AZT (20
      to 300 microM) for 6 days. 5-FU alone yielded an IC50 of 18 microM in the
      parental CCL 227 cell line and IC50s of 470 and 1100 microM in the 5-FU resistant
      cell lines as determined by a MTT chemosensitivity assay. Addition of 100 microM
      AZT alone, a drug concentration that can be achieved in patients, had no effect
      on the growth of the cell lines examined. However, when added simultaneously with
      5-FU, the IC50s of 5-FU synergistically decreased to 10 microM in the sensitive
      and to 360 or 760 microM in the resistant cell lines, respectively. Our results
      demonstrate that the combination of 5-FU with AZT synergistically inhibited the
      growth of 5-FU resistant cells, suggesting the use of 5-FU in combination with
      AZT for the treatment of 5-FU sensitive as well as resistant human colon tumors.

PMID- 8884812
TI  - Decreased DNA topoisomerase II alpha expression and cold-sensitive growth in a
      mouse mammary cancer cell line resistant to etoposide and doxorubicin.
AB  - A mouse mammary carcinoma FM3A cell line resistant to the DNA topoisomerase
      (topo) II-targeting agent, etoposide (VP-16), FM3A/VP-2B, had a markedly reduced
      growth rate at a low temperature (33 degrees C). The cells had the following
      properties: (a) FM3A/VP-2B, which had 24-fold higher resistance to VP-16 than its
      parental line, FM3A, was cross-resistant to doxorubicin, but not to a
      camptothecin derivative, CPT-11. (b) Cold-resistant revertants from FM3A/VP-2B, R
      6 and R-11, remained 8- to 9-fold more resistant to VP-16 and 2- to 3-fold more
      resistant to doxorubicin. (c) FM3A/VP-2B had one-fourth the level of topo II
      activity and one-third of the topo II alpha content and mRNA of FM3A. R-6 and R
      11, however, had levels similar to FM3A. (d) FM3A/VP-2B and FM3A had a 3-base
      deletion at position 4170 on one allele on the topo II alpha cDNA, but expression
      of the wild-type and the deletion allele was not appreciably changed in both cell
      lines. Decreased topo II alpha expression might have led to the acquisition of
      drug resistance to etoposide in FM3A/VP-2B, and appeared to be linked with the
      cold-sensitive growth. We also present a corrected mouse topo II alpha cDNA
      sequence.

PMID- 8884814
TI  - Reference listings in cancer research.

PMID- 8884813
TI  - alpha-(3,4-dimethyoxyphenyl)-3,4-dihydro-6,7-dimethoxy-alpha- [(4
      methylphenyl)thio]-2(1H)-isoquinolineheptanenitrile (CL 329,753): a novel
      chemosensitizing agent for P-glycoprotein-mediated resistance with improved
      biological properties compared with verapamil and cyclosporine A.
AB  - Agents that inhibit P-glycoprotein may restore sensitivity to some antitumor
      drugs in cancer patients. Optimization of the specificity and potency of one
      class of chemosensitizing agents related to verapamil has led to the
      identification of alpha-(3,4-dimethyoxyphenyl)-3,4-dihydro-6, 7-dimethoxy-alpha
      [(4-methylphenyl) thio]-2(1H)-isoquinolineheptanenitrile, designated CL 329,753.
      In vitro, 0.1 to 2.0 microM CL 329,753 restored sensitivity to drugs in the
      multidrug resistance (MDR) phenotype in cell lines that overexpress P
      glycoprotein. CL 329,753 was greater than 10-fold more potent and efficacious
      than cyclosporine A or verapamil in vitro, particularly in cells that express
      high levels of P-glycoprotein. The enhanced activity of CL 329,753 may be related
      to its inability to be transported by P-glycoprotein, since low drug accumulation
      of cyclosporine or verapamil but not CL 329,753 was found in P-glycoprotein
      containing cells, yet all three agents inhibited vinblastine binding to membranes
      containing P-glycoprotein and inhibited photoaffinity labeling of P-glycoprotein.
      In vivo, CL 329,753 resensitized drug-resistant tumors to vinblastine or
      doxorubicin in an ascitic or solid tumor model, respectively. No alteration in
      the plasma pharmacokinetic profile of doxorubicin by CL 329,753 has been found.
      Furthermore, the compound had 70-fold less calcium channel antagonistic activity
      compared with verapamil.

PMID- 8884815
TI  - Oral and maxillofacial pathology: what should we teach and how should we teach
      it?

PMID- 8884816
TI  - Tobacco use and cancer.

PMID- 8884817
TI  - Beta-carotene and lung cancer?

PMID- 8884818
TI  - An asymptomatic enlargement of the upper lip.

PMID- 8884819
TI  - Reconstruction of alveolar bone defects after extraction of mandibular third
      molars: a pilot study.
AB  - INTRODUCTION: A documented complication of mandibular third molar extraction is
      the development of bony defects on the distal aspect of the adjacent second
      molar. The primary study purpose was to determine the efficacy of grafting third
      molar extraction sites with demineralized bone powder to prevent the formation of
      periodontal defects. MATERIAL/METHODS: With a randomized clinical trial study
      design and a third molar extraction surgical model, we enrolled a study sample
      composed of patients who required extraction of bilateral third molars.
      Demineralized bone powder was placed in one randomly selected extraction site per
      patient. The remaining extraction site served as a control. Patients served as
      their own controls. To assess periodontal healing, we measured plaque and
      gingival indexes and periodontal attachment loss on the distobuccal aspect of the
      adjacent second molar preoperatively and 6 months postoperatively. RESULTS: Of 14
      patients enrolled, 7 patients with a mean age of 21.7 +/- 3.7 years completed the
      study protocol. No statistically significant differences were noted between
      patients who did and did not complete the study protocol (all p values > or =
      0.42). There were noted statistically significant differences for the various
      anatomic, operative, or periodontal measures between the control and treatment
      teeth preoperatively (all p values > or = 0.46). Six months postoperatively,
      there were no statistically significant changes in the plaque or gingival indexes
      for the control or experimental sites. At the control sites, there was a
      nonstatistically significant decrease in mean attachment loss from 3.1 +/- 1.3 mm
      preoperatively to 1.4 +/- 1.6 mm 6 months postoperatively (p = 0.06). At
      experimental sites, there was a statistically significant decrease in mean
      attachment loss from 3.3 +/- 1.4 mm preoperatively to 0.6 +/- 0.8 mm 6 months
      postoperatively (p = 0.02) CONCLUSIONS: The study results suggest that
      demineralized bone powder may decrease attachment loss on the distal aspect of
      the second molar after extraction of the adjacent third molar. Additional studies
      are indicated to confirm the results of this pilot study. We recommend that
      future studies limit their study samples to patients at high risk for developing
      periodontal defects after third molar extraction.

PMID- 8884820
TI  - Short retromandibular approach of subcondylar fractures: clinical and radiologic
      long-term evaluation.
AB  - OBJECTIVE: The classic technique for open reduction of subcondylar fracture is
      the submandibular approach. The aim of this study was to evaluate long-term
      clinical and radiologic results of the short retromandibular approach to
      displaced subcondylar fractures. MATERIAL AND METHODS: During a period of 66
      months we performed a prospective study with a modified version of the
      retromandibular approach in 38 patients with displaced subcondylar fractures. In
      this article we describe clinical and radiologic results in 19 patients with
      follow-ups longer than 6 months (range, 6 to 66 months). Preoperatively all
      patients had malocclusion and radiology demonstrated displacement. RESULTS: The
      retromandibular surgical approach was successful in all cases. Roughly 25 months
      after surgery, mouth opening was 43 mm with symmetric laterotrusive movements.
      Permanent marginal nerve palsy was never observed. CONCLUSIONS: Our findings
      indicate that the short retromandibular approach is an easy and safe technique
      for displaced subcondylar fractures.

PMID- 8884821
TI  - Anteriorly based palatal flap for closure of large oroantral fistula.
AB  - A technique for closure of large oroantral fistula as a lateral transposition
      flap with an anteriorly based palatal flap is described. Mucoperiosteum of the
      posterior third of the hard palate, which is more yielding, is raised to bridge
      large defects without leaving any considerable exposed raw area. The technique is
      particularly useful in the correction of defects at the tuberosity region.

PMID- 8884822
TI  - A comparison of mandibular angle fracture plating techniques.
AB  - OBJECTIVE: The purpose of this investigation was to compare the conventional
      technique of mandibular angle fracture plating with two biomechanically
      dissimilar techniques in their abilities to resist vertical loads similar to
      masticatory forces. STUDY DESIGN: Three groups of five synthetic hemimandibles
      with simulated fracture repairs were compared for their capabilities to resist
      vertical deformation. The conventional group was stabilized with a thin tension
      band system at the superior border and thick stabilization plate system at the
      inferior border. The nontraditional group was stabilized with a thick tension
      band system at the superior border and thin stabilization plate system at the
      inferior border. The two miniplate group was stabilized with a thin tension band
      system at the superior border and thin stabilization plate at the inferior
      border. A cantilever beam design was used. Testing was performed with an instron
      8511.20 (Instron Corp., Canton, Mass.) mechanical testing device. The three
      groups were compared with a two way analysis of variance. RESULTS: The forces
      resisted by the conventional group (167.6 +/- 18.2 N), the nontraditional group
      (156.3 +/- 33.9 N), and two miniplate group (154.0 +/- 18.4 N) were not
      statistically different (F = 0.44, p > 0.66). All failures occurred at the
      tension bands secured with monocortical screws. CONCLUSIONS: Under the conditions
      described in this in vitro investigation, plate thickness or pattern made no
      difference. All failures in this experiment occurred with monocortical screws in
      the superior border tension band system.

PMID- 8884823
TI  - Mortality associated with cervicofacial necrotizing fasciitis.
AB  - Cervicofacial necrotizing fasciitis is a rare infection but still occurs and
      carries a mortality rate up to 60%. It is a polymicrobial infection that is
      characterized by diffuse necrosis of fascial planes and subcutaneous tissues.
      Diagnosing early stages of cervicofacial necrotizing fasciitis in relationship to
      other soft tissue infections of odontogenic origin is difficult and leads to less
      aggressive treatment with resulting increased morbidity and mortality. To prevent
      this significant mortality and morbidity associated with cervicofacial
      necrotizing fasciitis early presentation, recognition and treatment by health
      care provider is essential.

PMID- 8884824
TI  - Effects of compliance with fluoride gel application on caries and caries risk in
      patients after radiation therapy for head and neck cancer.
AB  - The use of fluoride gel applied in a custom tray once daily has become standard
      for patients who have xerostomia after undergoing radiation therapy. Compliance
      may be poor as a result of the inconvenient method of application and because
      many patients with head and neck cancer have poor health behaviors. Our aim was
      to investigate the effect of compliance with fluoride gel application on caries
      and caries risk. Patients were prescribed neutral sodium fluoride gel (5000 ppm)
      before undergoing radiotherapy Fifty-two patients were willing to visit the
      dental clinic for dental examination, measurement of saliva, and quantitative
      culture of Streptococcus mutans and lactobacillus species. Before radiotherapy
      was performed, decayed, missing, and filled surfaces data were recorded for all
      patients in the study. Of these patients, 27 used fluoride gel once daily, as
      directed. Radiation dose, number of fractions, and duration of radiation had a
      significant inverse effect on postradiotherapy whole resting saliva (p = 0.04, p
      = 0.01, and p = 0.01) and on whole stimulated saliva (p = 0.02, p < 0.01, and p <
      0.01). Patients with a subjective feeling of dry mouth had significantly less
      saliva production at rest (p = 0.01) and on stimulation (p = 0.01). A trend
      toward reduction of S. mutans counts was seen in those patients who used their
      fluoride gel regularly (p = 0.057). High lactobacilli counts were found in the
      patients with high and low compliance with fluoride gel use. Differences in the
      mean caries incidence between those who reported compliance with daily fluoride
      application and those who did not comply were not found significant because of
      the large SD in the patient groups, although differences in the mean for these
      groups were seen. The lack of a statistically significant difference may be due
      to the multiple factors associated with caries. Therefore patient care must be
      individualized, and patients must be assessed at regular intervals to determine
      the caries risk and caries activity to provide guidance for maintenance of the
      dentition.

PMID- 8884825
TI  - Oral lesions as markers of severe immunosuppression in HIV-infected homosexual
      men and injection drug users.
AB  - OBJECTIVES: We examined the diagnostic utility of the presence of oral lesions,
      individually and in combination, in identifying severe immunosuppression, defined
      as CD4 cell count under 200. STUDY DESIGN: Data were collected on 82 HIV
      seropositive homosexual men and 82 HIV-seropositive injection drug users who
      volunteered to participate in a longitudinal study of HIV infection. CD4 cell
      counts were measured within 24 hours of oral examination. METHODS: Sensitivity,
      specificity, positive predictive value, negative predictive value, and the odds
      ratio were computed to assess the association between oral lesions and CD4 less
      than 200. In addition to the individual lesions, we studied the diagnostic
      properties of sets of three to six lesions. For each set of lesions, a patient
      was classified as positive for the set if he or she had one or more lesions in
      that set. RESULTS: In homosexual men and injection drug users, individual lesions
      had low sensitivity, high specificity, and moderate positive and negative
      predictive values. Odds ratios reflected weak correlation to immunosuppression.
      When lesion sets were considered in homosexual men, sensitivity rose dramatically
      with only modest decreases in specificity. The positive and negative predictive
      values remained almost the same. Similar results for lesion sets were obtained in
      injection drug users, with greater reduction in specificity but stable positive
      and negative predictive values. Odds ratios indicated that for homosexual men,
      the more lesions included in the set, the stronger the correlation with
      immunosuppression. For injection drug users, strong correlations were observed
      for all lesion sets. CONCLUSIONS: Analysis of sensitivities and odds ratios in
      homosexual men suggest that it may be valid to note the occurrence of a greater
      number of oral lesions than is currently done in staging patients with HIV
      infection. Among injection drug users, monitoring a larger number of lesions
      neither improves nor reduces the correlation to severe immunosuppression.

PMID- 8884826
TI  - Adult Chiari malformation with headache and trigeminal dysesthesia.
AB  - Arriving at a correct diagnosis in some cases of facial pain and headache can
      test the time, patience, and diagnostic skills of any clinician. When the
      symptoms are diffuse with few localizing signs, it is easy to attribute pain to a
      functional origin. The case described underlines the importance of careful
      clinical examination and the use of magnetic resonance imaging, which proved the
      only positive diagnostic aid in this instance. The value of magnetic resonance
      imaging in redefining Chiari malformations is discussed and the question of
      appropriate interpretation of findings aired.

PMID- 8884827
TI  - RET protooncogene mutational analysis in multiple endocrine neoplasia syndrome
      type 2B: case report and review of the literature.
AB  - Multiple endocrine neoplasia, type 2B (MEN 2B), is a phenotypic variant of a
      group of autosomal-dominant neurocristopathies. MEN 2B is associated with
      medullary thyroid carcinoma and pheochromocytoma with oral, ocular, and
      alimentary submucosal ganglioneuromas and Marfanoid body features. Approximately
      50% of cases are thought to be spontaneous mutations. The RET protooncogene (RET)
      is a 21-exon gene encoding a tyrosine kinase receptor. A codon 918 germ line
      mutation, which converts a highly conserved methionine to a threonine in the
      intracellular tyrosine kinase portion of this receptor of RET, has been
      identified in 95% of patients with MEN 2B. This mutation is easily detected by a
      direct deoxyribonucleic acid sequencing or restriction enzyme (Fok 1) analysis of
      amplified polymerase chain reaction products. The RET gene is normally expressed
      in the oral and gastrointestinal submucosal neural ganglia, and the codon 918
      mutation is thought to cause neuromas by virtue of its transforming activity in
      these ganglia. Identifying clinical features of MEN 2B in an 11-year-old boy by
      an oral pathologist led to confirmation by mutational analysis. Before genetic
      testing was available, the patient, and at a later date his mother, underwent
      thyroidectomies based solely on biochemical testing. Results indicated the
      patient had the codon 918 mutation, whereas his phenotypically normal mother,
      father, and older brother had normal RET analyses. Studies in families have
      demonstrated that the mutant allele is derived from the father with possible
      acquisition during spermatogenesis. We believe the mother of our affected patient
      to be normal; the absence of phenotypic features of MEN 2B and a normal genotype
      suggest her calcitonin abnormalities and minimal evidence for C-cell hyperplasia
      were inconsequential. Molecular analysis for RET abnormalities will likely
      supplant biochemical methods of diagnosis in patients with MEN 2B.

PMID- 8884828
TI  - Multiple hamartoma syndrome presenting with oral lesions.
AB  - Multiple hamartoma syndrome (Cowden's syndrome), a rare genodermatosis with
      predominant mucocutaneous features, particularly hamartomas, and Cowden/Lhermitte
      Duclos disease, the combination of multiple hamartomas with cerebellar
      hypertrophy, typically present with cutaneous and oral papillomatosis as major
      features of both uncommon disorders. This article details the clinical features
      of three patients with multiple hamartoma syndrome and one with both disorders.

PMID- 8884829
TI  - Palisaded encapsulated neuroma (solitary circumscribed neuroma) of the oral
      mucosa.
AB  - The objective of this study was to describe the clinical, histologic, and
      immunohistochemical features of 12 cases of palisaded encapsulated neuromas
      occurring on oral mucosa. The lesions were found in adults with a mean age of 54
      years (median 58 years), and the most common sites of involvement were the palate
      and the maxillary labial mucosa. On microscopic evaluation the lesions were well
      circumscribed, and the tumor cells were spindle-shaped with a fascicular and
      sometimes whorled pattern. The tumor cells were consistently intensely positive
      for S-100 protein.

PMID- 8884830
TI  - Unusual leiomyomatous hamartoma of the hard palate: a case report.
AB  - Harmartomas of the head and neck are common lesions, often taking the form of
      melanocytic nevi or vascular malformations such as hemangiomas and lymphangiomas.
      Hamartomas composed of other tissue types are much rarer and within the oral
      cavity are usually located on the tongue near the foramen cecum or on the
      anterior hard palate near the incisive papilla. Although most occur as isolated
      phenomena, a small number may be associated with other local developmental
      defects or with a syndrome complex. A normal 5-year-old girl had a 1 cm soft
      sessile swelling in the vault of the hard palate on the left side.
      Histopathologic examination showed bundles of smooth muscle embedded in
      fibrovascular stroma and accompanied by abundant mature fat and a small amount of
      salivary tissue. The features were regarded as those of a leiomyomatous hamartoma
      and could be distinguished from a smooth-muscle tumor, teratoma, and benign
      mesenchymoma by virtue of the clinical and histopathologic features. No
      recurrence has been seen after excision.

PMID- 8884831
TI  - DNA ploidy analysis of squamous cell carcinomas of the oral and maxillofacial
      region: clinical and pathologic correlations.
AB  - DNA ploidy was investigated in 61 specimens obtained from 25 patients with
      squamous carcinoma of the oral and maxillofacial region. Biopsy specimens of
      normal tissue surrounding the tumor were also obtained in six patients. Single
      cell suspensions for flow cytometric analysis were prepared. The DNA ploidy and
      histogram were calculated and compared with the histologic grade, presence of
      lymph node metastases, and course of the disease. The ploidy of the main stemline
      was peridiploid in 17 carcinomas, hyperdiploid in three, and aneuploid in five.
      Histologic grade but not nodal involvement was associated with the ploidy of the
      main stemline. Of 15 multisampled carcinomas 13 showed constant DNA ploidy and
      histogram classification. In the other two major changes in DNA ploidy (from
      peridiploid to hyperdiploid in the first and from peridiploid to aneuploid in the
      second) were found. Survival information was available for 24 patients. Ploidy
      values higher or lower than 2.5 c were strongly predictive of both overall (p <
      0.001) and relapse-free survival (p < 0.001). The lymph node status proved a
      powerful prognostic indicator (p = 0.014) but was not related to the relapse-free
      time of survival. Multiparametric evaluation of survival revealed an independent
      role of both DNA ploidy and nodal involvement in the prognosis of squamous
      carcinoma of the oral and maxillofacial region.

PMID- 8884832
TI  - Effect of smear layer on coronal microleakage.
AB  - The purpose of this study was to examine the effect of smear layer on coronal
      microleakage. Fifty-two single-rooted extracted human teeth with a straight root
      canal were chemomechanically prepared and equally divided into experimental
      groups A and B. The teeth in group B were treated with ethylenediamine
      tetraacetic acid and sodium hypochlorite to remove the smear layer. All teeth in
      the experimental groups were next obturated with gutta-percha and sealer. Finally
      they were tested for dye leakage with methylene blue. Linear and volumetric
      measurement of dye penetration was used to assess leakage. The results of this
      study suggest that the removal of smear layer significantly improves the
      tightness of the sealing in the coronal area.

PMID- 8884833
TI  - Lactate dehydrogenase activity in periodontal ligament cells stored in different
      transport media.
AB  - BACKGROUND: Maintaining viability of periodontal ligament cells is important
      after an avulsion injury occurs. OBJECTIVE: This study examined cell death and
      compared different transport media at varying times. Lactate dehydrogenase (LD)
      measurements were made on root surfaces of extracted teeth for evaluating the
      results of breakdown and necrosis of periodontal ligament cells. STUDY DESIGN:
      Teeth were divided into three groups. Each was immersed in one of the following
      storage media: Hanks balanced salt solution, Custodiol solution (an organ storage
      medium), or sterile saline solution. I.D. measurements (an indicator of cell
      death) were made at 2, 6, 24, 72, and 168 hours after extraction. RESULTS: When
      the LD levels were compared according to the time periods, a progressive increase
      of cell death was found to be statistically significant (p < 0.001). However,
      when the effects of both time periods and the kind of storage medium on the LD
      levels were examined, the LD levels of the saline solution storage medium were
      found to be significantly higher (p < 0.001) than that of the other two groups.
      CONCLUSIONS: Both Hanks balanced salt solution and Custodiol appeared to be
      suitable transport media for maintaining cell viability, whereas saline solution
      was not.

PMID- 8884834
TI  - Determination of location of root perforations by electronic apex locators.
AB  - OBJECTIVES: This study was conducted to evaluate the accuracy of two electronic
      apex locators, the Sono Explorer Mark 2 Junior (Hakusui, Osaka, Japan) and Apit 2
      (Osada, Tokyo, Japan) in detecting root perforations. The adequacy of radiographs
      for identifying root perforations was also assessed. STUDY DESIGN: Thirty-two
      extracted human teeth were perforated in the middle third of the root and
      embedded in alginate. Determination of all perforations were carried out with K
      files no. 25 attached to the apex locators tested. Two radiographs were taken at
      two angulations after each electronic measurement. The actual location of the
      file tip in relation to the perforation was determined with a stereomicroscope. A
      total of 512 radiographs were evaluated to attempt to identify root perforations.
      RESULTS: The mean distance of the file tip from the external outline of the root
      surface was short for both instruments. A statistical difference (p < 0.05) was
      found between the two apex locators in dry canals or if saline solution was
      present. There was no significant difference between the two instruments in the
      presence of sodium hypochlorite. Evaluators radiographically identified 45% of
      the root perforations when located in buccal-lingual directions. CONCLUSION:
      Under the in vitro conditions of this study, both devices determined the location
      of the perforations in an acceptable clinical range short of the root surface.
      Radiographs were found to be less reliable in identification of perforation
      locations.

PMID- 8884835
TI  - Measurement of blood flow with radiolabeled microspheres in reflected
      mucogingival flaps in cats.
AB  - To quantify and compare blood flow in maxillary mucogingival flaps, a total of 16
      cats (32 mucogingival specimens) were divided into two groups. In group I the
      blood flow in attached or reflected maxillary tissues were measured. In Group II
      the effects on blood flow were measured in reflected tissues after the injection
      of the following solutions: (1) saline solution; (2) 2% lidocaine plain; (3) 2%
      lidocaine with 1:50,000 epinephrine; (4) no injection. After an injection of 153
      Gadolinium microspheres into the left ventricle of the heart, the tissues were
      harvested and placed in a gamma counter. Group I had a mean blood flow value of
      34.4 ml/min/100 gm of tissue for the unreflected samples and 152.3 ml/min/100 gm
      of reflected tissue. The levels of blood flow in tissue samples in group II
      results were: no injection (control), 41.2 ml/min/100 gm; saline solution, 46.8
      ml/min/110 gm; 2% lidocaine with 1:50,000 epinephrine, 60.6 ml/min/100 gm; and 2%
      lidocaine plain, 90.2 ml/min/100 gm. On the basis of these results it appears
      that reflection of gingival tissue and injection of 2% lidocaine plain induces
      increased blood flow 90 minutes postoperatively.

PMID- 8884836
TI  - Assessment of the trabecular pattern before endosseous implant treatment:
      diagnostic outcome of periapical radiography in the mandible.
AB  - OBJECTIVES: To study the diagnostic outcome of periapical radiography in the
      assessment of the bone trabecular pattern of the mandible. STUDY DESIGN:
      Mandibular autopsy specimens were radiographed. Seven observers assessed the
      radiographs with the aid of a proposed classification with and without reference
      images and the classification presented by Lekholm and Zarb. Accuracy was
      estimated on the basis of morphometric measurements of trabecular bone volume.
      Observer agreement was calculated as the estimated probability of agreement
      between and within observers and as kappa index. RESULTS: With the classification
      proposed by us, the overall accuracy was 58% with and 50% without reference
      images. The accuracy for assessing dense trabeculation was higher (78%) than that
      for sparse trabeculation (28%). The accuracy of the proposed classification by
      Lekholm and Zarb was not possible to evaluate. The interobserver agreement varied
      between 49% and 64% and the intraobserver agreement between 75% and 86%.
      CONCLUSION: A new classification with reference images is recommended to assess
      the trabecular pattern in periapical radiographs before implant treatment.

PMID- 8884837
TI  - Diagnostic accuracy of direct digital dental radiography for the detection of
      periapical bone lesions: overall comparison between conventional and direct
      digital radiography.
AB  - OBJECTIVES: The diagnostic accuracy of direct digital radiography for the
      detection of small, experimentally made, periapical lesions was compared with
      that of E speed film. The high- and low-contrast resolutions of the imaging
      systems were also compared. STUDY DESIGN: The high-contrast resolution was
      evaluated with a line pair plate. The low-contrast resolution was determined with
      a contrast-detail plexiglass phantom. To evaluate the diagnostic accuracy, the
      periapical region of dry human mandibles was examined. Receiver operating
      characteristic based on the readings of seven observers were generated. RESULTS:
      The high-contrast resolution of the digital system was inferior, but the low
      contrast resolution was comparable to that of E-speed film. For diagnostic
      accuracy no significant difference was seen between the areas under the receiver
      operating characteristic curves. CONCLUSIONS: The quality of the direct digital
      images is comparable to that of E-speed film for the detection of periapical bone
      lesions.

PMID- 8884838
TI  - Ultrasonography evaluation of bone lesions of the jaw.
AB  - The ultrasonographic aspects of 72 intraosseous lesions of the jaws were
      evaluated to identify the usefulness of this type of examination. The principal
      aim of ultrasonography was to recognize the lesion's content before surgical
      treatment. Four groups of lesions were classified after the definitive
      histopathologic examination: lesions with solid, liquid, dense liquid, and mixed
      contents. The initial ultrasonography examination was in agreement with the
      histopathologic findings in 24 (92.3%) cases with solid content, 17 (73.9%) cases
      with liquid content, 7 (7.7%) cases with dense liquid content, and 13 (92.8%)
      cases with mixed content. On the basis of the results of this study, we propose
      the use of ultrasonography as a complementary examination for intraosseous
      lesions of the jaws. If a liquid component is identified in ultrasonography, a
      surgical procedure should be performed immediately. Otherwise, if a lesion with
      solid component is identified, it should be biopsied for histopathologic
      examination and final diagnosis before definitive surgery.

PMID- 8884839
TI  - Indications for debridement of necrotizing pancreatitis.

PMID- 8884840
TI  - What to do about sterile pancreatic necrosis?

PMID- 8884841
TI  - Fecal pancreatic elastase 1 is inaccurate in the diagnosis of chronic
      pancreatitis.
AB  - Many tests are available to assess pancreatic function. The ideal test would be
      simple and have adequate sensitivity in mild to moderate chronic pancreatitis
      (MCP) and severe CP (SCP). Fecal pancreatic elastase 1 (FPE1) assay (ScheBo Tech)
      has been proposed as a reliable test to evaluate pancreatic exocrine function,
      with sensitivities of up to 100% in diagnosing CP. Cutoff values (microgram/g
      stool) of < 100 have been suggested as SCP, 100-200 as MCP, and > 200 as normal.
      The test's ability to detect MCP distinguished by the absence of steatorrhea, and
      its specificity among various etiologies of malabsorption, has not been fully
      evaluated. The aim of this study was to evaluate this assay in subjects including
      patients with SCP with steatorrhea, patients with MCP with no steatorrhea,
      healthy controls, and diseased controls with nonpancreatic malabsorption. Thirty
      six subjects [15 healthy controls, 7 malabsorption controls, and 14 subjects with
      CP (7 MCP, 7 SCP)] had FPE1 assays. One hundred fifty-four assays for FPE1 were
      run for analysis. The intraassay and interassay intraclass correlation
      coefficients were 0.93 and 0.90, respectively. All SCP had values of < 100
      micrograms/g but more than half of the MCP subjects had FPE1 levels within the
      normal range. The subjects with nonpancreatic malabsorption had FPE1 values
      ranging from 55 to > 500 micrograms/g of stool. Although the assay detected SCP
      with steatorrhea, it did not consistently separate the MCP patients from normals.
      The majority of those with nonpancreatic malabsorption had false-positive values.
      These results may differ from previously described data because of the purposeful
      inclusion of MCP subjects, documented by the lack of steatorrhea, and the
      inclusion of disease controls with nonpancreatic malabsorption. Although PE1
      concentrates in the stool and is not significantly degraded, subtle changes in
      this enzyme, as in MCP, do not seem to be detectable by this assay. This group
      continues to be the most difficult group to diagnose clinically.

PMID- 8884842
TI  - Computed tomography of pancreatic adenocarcinoma: comparison of tumor size
      measured by dynamic computed tomography and histopathologic examination.
AB  - Our objective was to assess the detection rate and the accuracy of tumor size
      determination in pancreatic ductal adenocarcinoma using dynamic computed
      tomography (CT). Preoperative dynamic CT was evaluated in 35 surgically resected
      pancreatic ductal adenocarcinomas and the findings were compared with the results
      of histopathological examination. Pancreatic adenocarcinoma was visualized by
      dynamic CT as a low-density mass in 97% of cases. All three lesions < or = 2 cm
      in size were demonstrated in good contrast to normal pancreatic parenchyma. The
      tumor size measured on dynamic CT showed a good correlation with that measured
      histopathologically, especially in small tumors. Dynamic CT was useful for
      evaluating the extent of pancreatic adenocarcinoma, especially for small tumors.
      The detectability of lesions by CT depended on the manner of tumor extension and
      the degree of associated pancreatitis as well as the tumor size.

PMID- 8884843
TI  - Effect of antioxidants on postoperative hyperamylasemia in coronary bypass
      surgery.
AB  - Antioxidants may reduce pancreatic cellular injury after coronary artery bypass
      grafting (CABG) Twenty patients (Group A) received vitamin E (600 mg/ day) for 28
      days and vitamin C (2 g/day) and allopurinol (600 mg/day) 2 days before and 1 day
      after CABG. Seventeen patients (Group C) received all drugs for 3 days, and 25
      (Group B) and 19 (Group D) patients served as corresponding controls. The pre-
      and postoperative pancreatic isoamylase (P-amylase), creatinine, and antioxidant
      concentrations were measured. Serum hyperamylasemia was highest on the first
      postoperative day and occurred in 73% of the patients. After surgery serum P
      amylase increased in all study groups and urine P-amylase decreased.
      Postoperative serum hyperamylasemia, whether primarily renal or pancreatic,
      cannot be decreased by pretreatment with allopurinol, vitamin C, and vitamin E.

PMID- 8884844
TI  - p53 autoantibodies in patients with pancreatitis and pancreatic carcinoma.
AB  - In human pancreatic carcinoma (PCa) mutations in the p53 tumor suppressor gene
      are present in up to 50% of cases. Conformational change and cellular
      accumulation, together with subsequent release of mutant and normal p53 protein
      from transformed cells, may initiate a B-cell response with generation of
      circulating autoantibodies to p53 protein (anti-p53). In the present study we
      analyzed the sera of 85 consecutive patients with acute pancreatitis (N = 19),
      chronic pancreatitis (N = 33), and PCa (N = 33) to evaluate the specificity of
      autoantibodies to p53 protein as a serological marker for PCa. Detection of anti
      p53 was performed using an enzyme-linked immunosorbent assay system with
      immobilized recombinant wild-type p53 protein. Autoantibodies to p53 were
      detectable in 1 of 19 patients with acute (5.3%) and in 4 of 33 patients with
      chronic pancreatitis (12.1%). All anti-p53-positive patients with acute or
      chronic pancreatitis were carefully examined and no underlying malignant disease
      was found. During follow-up (range, 281-647 days; mean, 472 days) none of these
      patients showed any evidence for subsequent development of PCa or any other
      malignant disease. In patients with PCa, anti-p53 was detected in 6 of 33 cases,
      resulting in a sensitivity of 18.2% with a specificity of 90.4%. In contrast to
      anti-p53, detection of serum carbohydrate antigen (CA 19-9) resulted in a
      sensitivity and specificity of 69.7 and 71.2% (CA 19-9, > 37 U/ml) and 51.5 and
      96.2% (CA 19.9, > 100 U/ml) for the detection of PCa, respectively. Taken
      together, the sensitivity of anti-p53 formation was low in patients with PCa
      (18.2%). Furthermore, the detection of anti-p53 was not specific for malignancy,
      indicating that severe inflammatory processes may also induce anti-p53 formation.

PMID- 8884845
TI  - p53 protein expression and DNA ploidy in cystic tumors of the pancreas.
AB  - Cystic tumors of the pancreas form a heterogeneous group, with benign,
      premalignant, and malignant tumors. The molecular events that underlie their
      neoplastic transformation process are poorly understood. Our purpose was to study
      DNA ploidy by flow cytometry and p53 protein expression by immunohistochemistry
      in a large series of cystic tumors of the pancreas. The series of 51 surgical
      specimens included 18 serous cystadenomas, 20 mucinous cystic tumors (benign, n =
      14; borderline, n = 1; malignant, n = 5), 10 intraductal papillary-mucinous
      tumors (benign, n = 4; borderline, n = 1; malignant, n = 5), and 3 papillary and
      cystic tumors. The p53 protein immunohistochemical study was done in all cases on
      deparaffinized sections stained with the monoclonal antibody DO7. DNA flow
      cytometry was performed in 31 cases on formalin-fixed and paraffinembedded
      material. Neither p53 protein immunoreactivity nor DNA aneuploidy was observed in
      any case of serous cystadenoma. p53 protein overexpression was present in four of
      five malignant mucinous cystic tumors but was absent in benign and borderline
      cases. Only one case of malignant mucinous cystic tumor was DNA aneuploid. All
      benign and borderline intraductal papillary-mucinous tumors were p53 negative,
      and two of five malignant cases were p53 positive. There was no DNA aneuploidy in
      any case of intraductal papillary-mucinous tumors. The three cases of papillary
      cystic tumors showed neither p53 protein immunoreactivity nor DNA aneuploidy. In
      cystic tumors of the pancreas, p53 protein overexpression and DNA aneuploidy are
      rare events, restricted to malignant cases, mostly mucinous cystadenocarcinomas.
      Our results confirm that this group of tumors is heterogeneous and underline the
      need for earlier markers of an aggressive behavior.

PMID- 8884846
TI  - Eicosapentaenoic acid (C20:5) augments glucose-induced insulin secretion from
      beta-TC3 insulinoma cells.
AB  - There has been a large amount of recent literature suggesting that omega-3
      unsaturated fatty acids found in fish oils should be incorporated into the diet
      for the purpose of decreasing serum cholesterol levels. Inclusion of these fatty
      acids in the diet has been shown to decrease total serum cholesterol as well as
      low-density lipoprotein cholesterol. Some of these trials have been complicated
      by the fact that many of the subjects are afflicted with non-insulin-dependent
      diabetes mellitus. Unfortunately, the effects of omega-3 unsaturated fatty acids
      on insulin secretion have not been well characterized. In this study, we have
      examined the effect of a common omega-3 unsaturated fatty acid, eicosapentaenoic
      acid (C20:5), on insulin secretion. Using the beta-TC3 insulinoma cell line as a
      model system for studying insulin exocytosis, C20:5 selectively potentiated
      glucose-induced insulin secretion. At the same concentration at which it
      significantly increased glucose-induced insulin secretion, C20:5 did not affect
      glucose metabolism or intracellular free calcium concentrations. C20:5 also
      augmented potassium-induced insulin secretion. These data suggest that C20:5, an
      abundant omega-3 unsaturated fatty acid, acts to augment insulin secretion in a
      glucose-dependent manner.

PMID- 8884848
TI  - A rapid method to study heat shock protein 70-2 gene polymorphism in insulin
      dependent diabetes mellitus.
AB  - To examine the role of DNA loci within the human leukocyte antigen (HLA) region
      and insulin-dependent diabetes mellitus (IDDM), we studied fine mapping of HSP70
      2 gene. Polymerase chain reaction (PCR)-based genotyping was then developed and
      applied to type HSP70-2 in 59 patients with IDDM and 83 unrelated controls
      recruited from the inhabitants of northern Taiwan. Southern blot analysis
      revealed a diallelic PstI polymorphism of the HSP 70-2 gene, i.e., 9.6- and 8.5
      kb alleles. The polymorphic site was mapped in the intragenic PstI sequences
      (nucleotides 1051-1056) of the HSP70-2 gene. PCR-based restriction fragment
      length polymorphism studies revealed that the frequency of the 8.5-kb allele was
      increased in IDDM (56.8%, vs. 40.4% in controls; p < 0.009), with a relative risk
      of 1.93 (95% confidence interval = 1.20-3.11). The genotypic frequencies of
      9.6/9.6, 9.6/8.5, and 8.5/8.5 were 17.0, 52.5, and 30.5% for IDDM were different
      from those of controls (36.1, 47.0, and 16.9%, respectively; the homozygous 9.6/
      9.6 genotype was significantly decreased in the IDDM group, p < 0.02). In
      conclusion, we provide a simple, rapid, and nonradioactive method for HSP70-2
      genotyping. Our data confirmed that the 8.5-kb allele of HSP70-2 was associated
      with IDDM susceptibility in the Taiwanese population.

PMID- 8884847
TI  - Increased storage and secretion of islet amyloid polypeptide relative to insulin
      in the spontaneously diabetic GK rat.
AB  - We have investigated whether a possible dysregulation of the storage and function
      of islet amyloid polypeptide (IAPP) in the endocrine pancreas of 4-month-old
      spontaneously diabetic Goto-Kakizaki (GK) rats might contribute to the impairment
      of glucose-induced insulin secretion previously reported in these rats.
      Immunocytochemical studies indicated a significantly lower degree of labeling per
      beta-cell granule of insulin but not of IAPP in GK islets compared to control
      islets. Further, the GK rats displayed lower plasma levels of both insulin and
      IAPP in the fasting state. The pancreatic concentrations of both IAPP and insulin
      were also significantly lower in the GK rats than in the controls. Following an
      intraperitoneal glucose injection, the plasma IAPP and insulin concentration of
      the GK rats did not increase at all, whereas a significant increase in both IAPP
      and insulin concentration was recorded in the control animals. However, the
      plasma IAPP/insulin ratio was significantly higher in the GK rats at both 30 and
      60 min after glucose injection, which may be a reflection of an increased
      negative feedback effect of IAPP on insulin release. A relative hypersecretion of
      IAPP might be one of several factors contributing to the impairment of glucose
      induced insulin secretion in this rat model of non-insulin-dependent diabetes
      mellitus. This is further supported by our electron microscopic observations
      showing disproportionate IAPP/insulin labeling of beta-cell granules in the GK
      islets.

PMID- 8884849
TI  - Ligand-induced regulation of glucagon-like peptide-I receptor function and
      expression in insulin-secreting beta cells.
AB  - Glucagon-like peptide-I (GLP-I) is a potent incretin hormone and mediates its
      actions via the cyclic AMP (cAMP) pathway. The GLP-I receptor belongs to the
      family of seven-transmembrane domain receptors coupled to G proteins. We have
      analyzed the regulation of GLP-I receptor function and expression by its own
      ligand and the cAMP-dependent pathway in rat insulinoma-derived beta cells
      (RINm5F). The GLP-I receptor underwent rapid homologous desensitization, which
      occurred at the receptor level. This was characterized by a reduced binding
      capacity not mediated by protein kinase A (PKA). GLP-I receptor mRNA levels were
      down-regulated during incubation of cells by agents increasing cAMP levels
      including GLP-I itself. This effect was dependent upon time and concentration.
      Forskolin, the PKA activator 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole-3,
      5-monophosphorothiotate, and GLP-I stabilized the GLP-I receptor mRNA. All
      induced down-regulation of the GLP-I receptor number within 3 h, a time point at
      which GLP-I receptor mRNA levels were not decreased. This effect was not
      influenced by cycloheximide. Therefore, in addition to transcriptional effects,
      posttranslational mechanisms exist to regulate GLP-I receptor numbers in insulin
      secreting cells.

PMID- 8884850
TI  - Effects of a bradykinin receptor antagonist (HOE140) on taurocholate-induced
      acute pancreatitis in rats.
AB  - The effect of a potent and long-acting bradykinin B2-receptor antagonist (HOE140)
      on acute pancreatitis induced by retrograde infusion of trypsin and taurocholate
      into the pancreatic duct was studied in rats. HOE140 was administered
      subcutaneously immediately before and 3 h after the induction of pancreatitis and
      the systemic blood pressure, ascites volume, serum amylase, 24-h survival rate,
      and pathology of the pancreas were evaluated. Plasma concentrations of bradykinin
      increased significantly 15 min after the induction of pancreatitis and decreased
      to basal levels at 90 min. HOE140 (0.1 mg/kg) alleviated hypotension developing
      immediately after the induction of pancreatitis and reduced the ascites volume.
      The 24-h survival rate in rats treated with 0.1 mg/kg HOE140 (70.3%) was
      significantly higher than that in controls (35.6%). Treatment with 0.01, 0.3,
      1.0, and 3.0 mg/kg of HOE140, however, had no beneficial effect on the survival
      rate. Ascites volume, serum amylase, and pathology of the pancreas at 24 h were
      not improved by treatment with HOE140. These data suggest that HOE140 may improve
      the survival rate by maintaining hemodynamics in the early stage of experimental
      acute pancreatitis.

PMID- 8884851
TI  - Measurement of pancreatic blood flow with the intraductal electrode method of the
      hydrogen clearance technique in acute pancreatitis in rats.
AB  - Measurement of local pancreatic blood flow during acute pancreatitis is thought
      of as being technically difficult in smaller animals. In this study, we first
      employed an intraductal electrode method of the hydrogen clearance technique for
      measurement of changes in local pancreatic blood flow in two types of acute
      pancreatitis in rats, then compared this method with an interstitial electrode
      method that has been used in rats. There was a very close correlation between
      these methods (r = 0.998, p < 0.001). The intraductal electrode method was easily
      performed and caused minimal tissue damage.

PMID- 8884852
TI  - Correlative morphometric and biochemical study on pancreatic amylase in normal
      and streptozotocin-diabetic rats.
AB  - The number, volume, and size of zymogen granules in pancreatic acinar cells of
      normal and streptozotocin-diabetic rats were measured using stereological
      techniques. These morphometric data were then correlated with the amylase
      activity of the acinar cells. In the normal rats, the acinar cells had a mean
      volume of 1,253.5 microns 3 and contained 343 zymogen granules, which occupied a
      volume of 103 microns 3 of the cell (8.28%). In the diabetic rats, the mean
      acinar cell volume was estimated as 1,017 microns 3 and the cell contained 220
      zymogen granules, which occupied a volume of 55.8 microns 3 (5.38%). The cell
      volume and zymogen granule number and volume were 19, 36, and 46%, respectively,
      more in normal rat pancreas, while no difference in the size of zymogen granules
      between normal and diabetic rats was observed. On the other hand, the volume
      density and numerical densities of acinar cell nuclei were slightly larger in the
      diabetic rats, but no differences in the nuclear size between normal and diabetic
      rats were recorded. Biochemically, the amylase activity of diabetic rat pancreas
      was 37% less than that of normal rats. The present results indicate the
      impairment of pancreatic amylase production in streptozotocin-diabetic rats, and
      the correspondence between the morphometrical and the biochemical data indicates
      that amylase is processed intracellularly in membrane-bound compartments.

PMID- 8884853
TI  - Effect of somatostatin and octreotide acetate on OP-CCK-stimulated exocrine
      secretion in the denervated canine pancreas.
AB  - Somatostatin and its analogue, octreotide acetate (Sandostatin), have been
      demonstrated to suppress exocrine secretion in a denervated canine pancreatic
      autograft model. To help define this inhibitory mechanism, the effect of these
      agents on cholecystokinin (CCK)-stimulated acinar cell secretion was evaluated.
      In vitro assessment evaluated the effect of somatostatin on octapeptide (OP)-CCK
      stimulated amylase release of pancreatic tissue slices. In vivo assessment
      employed animals with pancreatic autografts and pancreaticocystostomies,
      evaluating the effect of a bolus intravenous injection of 100 micrograms of
      octreotide acetate on the basal and OP-CCK-stimulated (125 ng/kg/h) secretion of
      urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with
      0.16, 0.24, or 0.32 microgram/ml somatostatin had no significant effect on in
      vitro OP-CCK-simulated amylase release. Intravenous octreotide acetate resulted
      in a significant decrease in the basal rate of amylase secretion but had no
      significant effect on OP-CCK-stimulated autograft amylase or bicarbonate release.
      These studies demonstrate that octreotide acetate has an in vivo inhibitory
      effect on basal amylase release of pancreatic autografts but cannot counteract
      maximal stimulation with exogenous OP-CCK. Also, somatostatin does not inhibit OP
      CCK-stimulated acinar cell secretion of pancreatic tissue slices. These results
      indicate that the exocrine inhibition produced by somatostatin analogues in the
      grafted pancreas occurs via an indirect mechanism.

PMID- 8884854
TI  - Visualization and characterization of CCK receptors in exocrine pancreas of rat
      with storage phosphor autoradiography.
AB  - Studies on cholecystokinin (CCK) receptors in rat pancreas are usually performed
      on homogenates. Using storage phosphor autoradiography, a new imaging technique
      with a high sensitivity and large linear dynamic range, we visualized and
      characterized CCK receptors in tissue sections of normal rat pancreas. The
      density of CCK receptors in pancreatic tissue sections from 10 normal rats
      appeared to be unevenly distributed and variable in serial sections. The binding
      of labeled CCK-8 was markedly inhibited by CCK-8 and CCK-A receptor antagonists,
      but it was only weakly affected by gastrin and CCK-B receptor antagonists. At
      room temperature the CCK-8 dose-inhibition curve was fitted by a two-site model:
      one with a high-affinity but low-capacity site and another with a low-affinity
      but high-capacity site. The CCK-8 dose-inhibition curve showed that the
      inhibition of the variable high-density receptors took place at a low
      concentration of CCK-8, while the diffuse low-density receptors were inhibited at
      the high concentration of 1 microM CCK-8. Binding of labeled CCK-8 at 37 degrees
      C was homogeneous with a low affinity and comprised only 4% of that found at room
      temperature. In summary, an uneven density of CCK receptors in the rat exocrine
      pancreas was observed and attributed to the variable expression of high-affinity
      CCK receptors in pancreatic acini.

PMID- 8884855
TI  - Ethanol inhibits CCK-induced enzyme secretion by affecting calcium-pump activity
      in isolated rat pancreatic acini.
AB  - The aim of this study was to clarify the effect of ethanol on stimulus-secretion
      coupling in pancreatic exocrine secretion. We investigated the effects of 600 mM
      ethanol on cholecystokinin octapeptide (CCK-8)-stimulated amylase release,
      cytosolic free Ca2+ concentration ([Ca2+]i) and Ca2+ fluxes using in vitro
      isolated rat pancreatic acini. Ethanol, given alone, stimulated both the initial
      and the sustained phases of amylase release. On the other hand, ethanol inhibited
      only the sustained phase of amylase release stimulated by CCK-8. Ethanol also
      inhibited amylase release in response to fluoride, a direct activator of guanine
      nucleotide-binding protein, suggesting that ethanol affects intracellular signal
      transduction molecules. Ethanol had no influences on the initial rise but
      increased the sustained rise in [Ca2+]i stimulated by CCK-8 and inhibited CCK-8
      stimulated Ca2+ outflux without affecting Ca2+ influx. 8-Bromoguanosine 3':5'
      cyclic monophosphate, a membrane-permeable analogue of cGMP regulating membrane
      Ca(2+)-pump activity in various cells, completely reversed the ethanol-induced
      inhibition of amylase release and Ca2+ outflux in response to CCK-8 as well as
      fluoride. Given that Ca2+ plays a critical role in stimulus-secretion coupling in
      pancreatic exocrine secretion, our results indicate that 600 mM ethanol inhibits
      CCK-8-stimulated amylase release by inhibiting Ca(2+)-pump activity on the plasma
      membrane.

PMID- 8884856
TI  - Acute pancreatitis induced by codeine-acetaminophen association: a case report
      with positive rechallenge.

PMID- 8884857
TI  - Pancreatic B-cell replication in an animal model of insulin-resistant non-insulin
      dependent diabetes mellitus.

PMID- 8884858
TI  - Cerebral monitoring during cardiopulmonary bypass.

PMID- 8884859
TI  - Efficacy and safety of aprotinin in aortocoronary bypass and valve replacement
      operations: a placebo-controlled randomized double-blind study.
AB  - To assess the efficacy and safety of the use of a high-dose regimen of aprotinin
      in routine cardiac operations, a placebo-controlled randomized double-blind study
      was conducted in 93 adult patients undergoing cardiopulmonary bypass. Aprotinin
      treated patients (group A, n = 46) received 2 x 10(5) Kallikrein Inactivating
      Units (KIU) of aprotinin before incision, 2 x 10(6) KIU in the priming solution
      and 5 x 10(5) KIU/h during CPB. Control patients (group B, n = 47) received the
      same volume of normal saline. Mean postoperative blood loss in ml after six hours
      and in total until removal of thoracic drains decreased significantly from 752
      and 1933 in controls, to 358 and 1051 in treated patients (p < 0.001). Mean total
      transfusion needs were 2.6 (A) and 4.8 (B) units per patient. Adverse events were
      evenly distributed between both groups and could not be attributed to aprotinin
      use. We, therefore, recommend the use of a high-dose regimen of aprotinin for
      routine cardiac operations despite its cost.

PMID- 8884860
TI  - The use of a load cell for continuous cardiotomy reservoir level measurement
      during cardiopulmonary bypass.
AB  - We have examined the use of a 6 kg strain-gauge load cell for the purpose of
      continuous measurement of cardiotomy reservoir volume during cardiopulmonary
      bypass. It performed reliably and reproducibly and was found to be simple to
      interface to an anaesthesia monitor. The resolution of the cell was +/- 15 ml and
      the bias and limits of agreement for a series of 221 measurements were +15 ml and
      175 ml, respectively. A continuously available digital level signal can present
      significant advantages to the perfusionist. The signal can be presented remotely
      in the form of a bar graph or a digital display, or can be interfaced to an
      intelligent alarm system which can be triggered on the basis of "time to expected
      reservoir exhaustion' rather than absolute reservoir level. The alarm state can
      also be conveyed in spoken form using speech synthesis. Finally, when recorded by
      an automatic record keeping system, the reservoir level constitutes an important
      addition to the perfusion record.

PMID- 8884861
TI  - Complement activation during and after open-heart surgery is only marginally
      affected by the choice of fluid for volume replacement.
AB  - Forty patients undergoing CPB for coronary artery surgery, using a standardized
      technical setting, were randomized to receive either Ringer's acetate, dextran 70
      (Macrodex), polygeline (Haemaccel) or albumin 4% for volume replacement during
      and after surgery. The choice of fluid did not affect early complement activation
      (C3 activation products). Higher values of the terminal complement complex (TCC)
      were found only at the end of the operation in patients receiving polygeline.
      There were no differences between any two of the four groups during the
      postoperative course. The use of blood transfusion or autotransfusion and the
      degree of haemodilution and hypothermia did not affect complement activation. We
      conclude that complement activation in association with open-heart surgery is
      only marginally affected by the choice of fluid for volume replacement.

PMID- 8884862
TI  - Complement consumption during cardiopulmonary bypass: comparison of Duraflo II
      heparin-coated and uncoated circuits in fully heparinized patients.
AB  - Heparin attachment to synthetic surfaces is one means of improving the
      biocompatibility of clinically used cardiopulmonary bypass (CPB) circuits. To
      assess the effect of heparin-coated circuits on complement consumption during
      CPB, 40 patients undergoing elective myocardial revascularization were
      prospectively randomized either to a group in which a completely Duraflo II
      heparin-coated circuit was used for perfusion (heparin-coated Group, n = 20
      patients) or to a control group (n = 20 patients) in which an uncoated, but
      otherwise standard circuit was used. Full systemic heparinization was induced
      (activated clotting time, 480 seconds) in all the patients included in the study,
      regardless of which perfusion circuit was used. The two groups did not differ
      significantly in terms of bodyweight, aortic crossclamp and extracorporeal
      circulation times. No patient had difficulty in weaning from bypass and the
      postoperative period was uneventful in all patients. Concentrations of C3 and C4
      were found to be within the "normal' range in the prebypass period in both
      groups. There were no significant intergroup differences with regard to C3 and C4
      consumption during CPB. We conclude that Duraflo II heparin-coated circuits have
      no effect in reducing complement consumption during CPB in fully heparinized
      patients.

PMID- 8884863
TI  - Lipoproteins in heart disease.
AB  - Most lipids are carried in the circulation by lipoproteins. Lipoproteins and
      their associated proteins, called apolipoproteins, are currently being studied in
      an effort to further our understanding of atherosclerotic cardiovascular disease.
      Lipoprotein assembly, secretion, transportation, modification and clearance are
      essential elements of healthy lipid metabolism. When one or more of these key
      steps becomes altered, various disease states are induced. Current data suggest
      that lipoprotein(a), a low density lipoprotein (LDL)-like particle, is an acute
      phase reactant that plays a critical role in the modulation of fibrinolysis.
      Several aspects of lipoproteins and lipoprotein metabolism will be examined.
      Emphasis will be placed on the proatherogenic and thrombogenic effects of
      oxidized LDL.

PMID- 8884864
TI  - Effects of cardiopulmonary bypass on systemic vascular resistance.
AB  - During cardiopulmonary bypass (CPB), complex neuroendocrine responses occur and
      result in haemodynamic changes. Systemic vascular resistance (SVR) before,
      during, and after CPB was documented in patients undergoing coronary artery
      bypass surgery. Whilst the overall effect was an increased SVR, transient
      profound decreases in SVR at the commencement of CPB, during the rewarming phase,
      and immediately on weaning off CPB were demonstrated.

PMID- 8884865
TI  - Single pump mechanically aspirated venous drainage (SPMAVD) for cardiac
      reoperation.

PMID- 8884866
TI  - Cadmium-metallothionein nephrotoxicity is increased in genetically diabetic as
      compared with normal Chinese hamsters.
AB  - To investigate the extra susceptibility of diabetics to some nephrotoxic agents,
      adult normal and diabetic Chinese hamsters (6-7 animals in each group) were
      injected subcutaneously with different doses of cadmium-metallothionein (Cd-MT)
      equivalent to 0.0, 0.1 or 0.25 mg Cd/kg body weight and the first 24 hr urinary
      outputs were collected. Several days prior to exposure to the Cd-MT the diabetic
      hamsters were hyperglycaemic, and plasma insulin levels and body weights were
      elevated in some of the diabetics. The higher dose of Cd-MT caused significant
      spillage of N-acetyl-beta-glucosaminidase (U-NAG) activity and protein into the
      urine of both normal and diabetic animals. The higher dose of Cd-MT was more
      toxic to the diabetic kidneys because U-NAG levels were higher in the diabetics
      (2.5-fold higher than normal). U-Cd levels were proportional to the injected Cd
      MT dose. U-Zn levels were not consistently affected by the injected Cd-MT
      although it had contained small amounts of Zn. Therefore, genetic diabetes in the
      Chinese hamster appears to increase susceptibility to acute cadmium-MT
      nephrotoxicity. The mechanisms underlying this need to be further investigated.

PMID- 8884867
TI  - Lysosomal storage of sulphated glycosaminoglycans induced by dicationic
      amphiphilic drug molecules: significance of the central planar ring system.
AB  - The immunomodulatory drug tilorone (2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one)
      and several congeners are known to disturb the lysosomal degradation of sulphated
      glycosaminoglycans and thereby induce lysosomal storage of glycosaminoglycans in
      cultured cells and intact organisms. The molecules of tilorone and congeners
      consist of a planar aromatic ring system symmetrically substituted with two
      aliphatic side chains each carrying a protonizable nitrogen. In a previous study
      it was proposed that non-degradable glycosaminoglycan-drug complexes are formed
      by electrostatic interactions and that additionally intermolecular interactions
      between the drug molecules due to electronic coupling of their central planar
      ring system are important for formation and stabilization of the
      glycosaminoglycan-drug complexes and thus for the drug side effect in question.
      The significance of the central planar ring system was tested in the present
      study by comparing tilorone and the compound bis(beta-diethylamino
      ethylether)hexestrol (DH) with respect to their potencies to cause lysosomal
      glycosaminoglycan storage in cultured bovine corneal fibroblasts. DH has the same
      side chains as tilorone, but its central apolar moiety lacks planarity. At a
      concentration (1.75 muM) which did not cause enhanced secretion of the lysosomal
      enzyme beta-hexosaminidase (E.C. 3.2.1.52), DH was significantly less potent than
      tilorone in causing storage of [35S]glycosaminoglycans. This is taken as support
      of the hypothesis that the planar tricyclic ring system is essential for the high
      potency of tilorone and its congeners to exert this adverse action.

PMID- 8884868
TI  - Ethanol interference with morphine metabolism in isolated guinea pig hepatocytes.
AB  - It has previously been shown that guinea pig hepatocytes metabolise morphine in a
      fashion similar to humans. The metabolism of morphine (5 muM) and the formation
      of metabolites morphine-3-glucuronide, morphine-6-glucuronide and normorphine was
      studied in the absence and presence of ethanol (5, 10, 25, 60 and 100 mM) in
      freshly isolated guinea pig hepatocytes. In order to gain more detailed
      information, a mathematical model was estimated on experimental data and used to
      analyse the effects of ethanol on the reaction rates of the different morphine
      metabolites. Ethanol inhibited the rate of morphine elimination in a dose-related
      manner, at the high ethanol concentrations the elimination rate was 40 per cent
      of the control rate. The formation of morphine-glucuronides was influenced in a
      biphasic manner. Five and 10 mM ethanol increased both the morphine-3-glucuronide
      and morphine-6-glucuronide levels after 60 min incubation compared to the
      control, whereas at the higher ethanol concentrations (25-100 mM) the levels of
      morphine-glucuronides were reduced. Data from the mathematical model, however,
      demonstrated that the reaction rates for morphine-glucuronide formation were
      decreased at all ethanol concentrations and in a dose-dependent manner, the
      interpretation of this being that at the lower (5 and 10 mM) ethanol
      concentrations employed in this study, other metabolic pathways of morphine are
      more heavily inhibited than the glucuronidations, resulting in a shunting towards
      morphine-3-glucuronide and morphine-6-glucuronide. The pharmacodynamic
      consequences of these pharmacokinetic effects are thus somewhat difficult to
      predict since morphine-6-glucuronide has a higher agonist potency than morphine.
      At high concentrations ethanol inhibition of morphine metabolism will increase
      the concentration of morphine and subsequently the euphoric and the toxic
      effects. The lower quantities of morphine-6-glucuronide formed in the presence of
      high ethanol concentrations on the other hand most probably imply reduction of
      such effects and the net pharmacodynamic effect would be uncertain. At low
      ethanol concentrations, however, morphine-6-glucuronide concentrations increased
      and morphine metabolism was less inhibited leading to a possible potentiation of
      the effects of morphine. Thus, a low ethanol concentration might exert a more
      pronounced ethanol-drug effect interaction than a higher ethanol concentration.

PMID- 8884869
TI  - Effects of ethanol and acetate on adenosine production in rat hippocampal slices.
AB  - Since adenosine has been shown to mediate some actions of ethanol we have
      examined the effect of ethanol (20 and 80 mM) or its metabolite acetate (5 and 20
      mM) on the formation and release of adenosine by rat hippocampal slices. The ATP
      pool of the slices was radioactively labelled by preincubation with [3H]-adenine.
      The efflux of radioactivity under basal conditions and following ATP breakdown
      induced by combined hypoxia/hypoglycaemia was examined. Ethanol or acetate did
      not increase the total efflux of [3H]-purines, but changed the composition to a
      larger proportion of [3H]-adenosine. The release of endogenous adenosine was also
      increased. This type of effect exactly mirrors that previously reported for
      purine nucleoside transport inhibitors. The present results thus show that
      ethanol (20 mM) can increase adenosine release from a brain slice by a mechanism
      that probably involves transport inhibition.

PMID- 8884870
TI  - Evaluation of the specificity and potency of a series of cholecystokinin
      B/gastrin receptor antagonists in vivo.
AB  - The potency and specificity of five proposed cholecystokinin-B receptor
      antagonists, YM022, RP73870, L-740,093, L-365,260 and LY288513, were studied in
      rats and mice. Gastrin activates rat stomach histidine decarboxylase via
      cholecystokinin-B/gastrin receptors. To examine cholecystokinin-B receptor
      mediated effects of the five drugs, they were infused intravenously to fasted
      rats and the histidine decarboxylase activity in the oxyntic mucosa was
      determined. While YM022, RP73870, L-740,093 and L-365,260 failed to activate
      histidine decarboxylase, they dose-dependently antagonized the gastrin-induced
      histidine decarboxylase activation. LY288513 had no effect in the doses tested.
      The maximal inhibitory effect of L-365,260, L-740,093, RP73870 and YM022 on
      histidine decarboxylase, activated by the intravenous infusion of an ED50 does of
      gastrin (0.4 nmoles/kg/hr), was seen at doses of 3, 0.3, 0.1 and 0.1
      mumoles/kg/hr, respectively; the corresponding ID50 values were 0.4, 0.02, 0.007
      and 0.004 mumoles/kg/h. In a follow-up study, YM022 and RP73870 were found to
      produce a rightward shift of the gastrin dose-response curve, which is consistent
      with competitive inhibition. The effect of the five drugs on a cholecystokinin-A
      receptor-mediated response was examined by studying gastric emptying in mice.
      Cholecystokinin-8s, given by a subcutaneous bolus injection, dose-dependently
      inhibits gastric emptying. The specific cholecystokinin-A receptor antagonist
      devazepide (given intravenously as a bolus injection) antagonized the effect of
      cholecystokinin-8s in a dose-dependent manner, with an ID50 value of 28
      nmoles/kg. None of the drugs inhibited the gastric emptying or prevented the
      cholecystokinin-8s-induced effect at the doses tested. The results indicate that
      YM022, RP73870, L-740,093 and L-365,260 act as cholecystokinin-B receptor
      antagonists in vivo, being without measurable agonistic activity. Furthermore,
      they do not interact with cholecystokinin-A receptors at te doses tested. Among
      the cholecystokinin-B receptor antagonists studied YM022 and RP73870 are
      superior, the rank order of potency being YM022 > or = RP73870 > L-740,093 > L
      365,260.

PMID- 8884871
TI  - Teratogenicity of a single oral dose of retinyl palmitate in the rat, and the
      role of dietary vitamin A status.
AB  - Vitamin A, known for its teratogenic properties, may be present in high
      concentrations in consumption liver. It is as yet unclear whether congenital
      malformations can result from a single liver meal. In our first experiment, the
      teratogenicity of a single dose of retinyl palmitate was tested in the rat.
      Pregnant rats were treated at day 10 of gestation by gavage with 100, 300 or 1000
      mg/kg body weight retinyl palmitate on a dietary background level of 5 mg/kg
      feed. At gestation day 11 the number of embryos with an open cranial neural tube
      had increased with the dose. At gestation day 21, the high dose group showed an
      increase in late resorptions, whereas both the high and the medium dose groups
      had a high incidence of foetuses with malformations typical of retinoid
      embryopathy. The data suggest that delayed neural tube closure had occurred in a
      large proportion of the embryos. In a second experiment, the high oral dose was
      applied on gestation day 10 in pregnant rats receiving retinyl palmitate at 1.5,
      5, 15, or 50 mg/kg feed for 6 weeks. Delayed neural tube closure, post
      implantation loss and the nature and incidence of malformations were similar
      between diet groups, as well as being reminiscent of the high dose group in the
      first experiment. Thus the dietary status of the animals did not seem to
      influence the teratogenic potential of a single high dose of retinyl palmitate.

PMID- 8884872
TI  - Effect of mercuric chloride intoxication and dimercaprol treatment on delta
      aminolevulinate dehydratase from brain, liver and kidney of adult mice.
AB  - Dimercaprol is a compound used in the treatment of mercury intoxication, however
      with low therapeutic efficacy. It is assumed that dimercaprol acts by
      reactivating target sulfhydryl-containing proteins. In the present investigation
      we studied the inhibitory effect of mercuric chloride treatment (3 days with 2.3
      or 4.6 mg/kg HgCl2, sc) in mice on cerebral, renal and hepatic delta
      aminolevulinate dehydratase (ALA-D) activity, and a possible reversal of the
      effect of mercury by dimercaprol (0.25 mmol/kg, 24 hr after the last mercury
      injection). Mercuric chloride did not inhibit cerebral ALA-D at the doses
      injected. Dimercaprol treatment did not restore the normal enzyme activity of the
      liver after the 25% inhibition caused by 4.6 mg/kg HgCl2. In the kidney,
      dimercaprol enhanced the inhibitory effect of 4.6 mg/kg mercuric chloride (from
      35% after mercury treatment alone to 65% after mercury plus dimercaprol
      treatment). Mercury content increased in kidney after exposure to 2.3 or 4.6
      mg/kg and the levels attained were higher than in any other organ Mercury
      accumulated in liver only after exposure to 4.6 mg/kg HgCl2, and dimercaprol
      further increased mercury deposition. Dimercaprol treatment also increased the
      levels of mercury in brain of animals exposed to 4.6 mg/kg HgCl2 The enzymes from
      all sources presented similar sensitivity to the combined effect of HgCl2 and
      dimercaprol in vitro. In the absence of preincubation, 0-500 muM dimercaprol
      potentiated the inhibitory effect of HgCl2 on ALA-D activity. In the presence of
      preincubation, and 100 and 250 muM dimercaprol enhanced ALA-D sensitivity to
      mercury, whereas 500 muM dimercaprol partially protected the enzyme from mercury
      inhibition. Dimercaprol (500 muM) inhibited renal and hepatic ALA-D when
      preincubated with the enzymes. These data suggested that the dimercaprol-Hg
      complex may have a more toxic effect on ALA-D activity than Hg2+. Furthermore,
      the present data show that dimercaprol did not acts by reactivating mercury
      inhibited sulfhydryl-containing ALA-D, and that indeed it may have an inhibitory
      effect per se depending on the tissue.

PMID- 8884873
TI  - Bioavailability of recombinant human growth hormone in different concentrations
      and formulations.
AB  - Whether the bioavailability of growth hormone depends on the concentration or
      formulation of the preparation was evaluated in 18 growth hormone-deficient
      patients. The design was a single-blinded, randomized cross-over study, where the
      patients were given a single, fixed dose subcutaneous injection of growth homrone
      (3 IU/m2) of 3 different preparations: (1) 4 IU/ml in a bicarbonate buffer
      dissolved in 0.9% benzyl alcohol (approximately 1.37 mg/ml), (2) 5.9 IU/ml in a
      phosphate buffer dissolved in 1.5% benzyl alcohol (approximately 2 mg/ml) and (3)
      11 7 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (approximately
      4 mg/ml). Conventional growth hormone-therapy was withdrawn 2 days before each
      study period. Blood samples were drawn over a 24-hr period and assessed for
      growth hormone, serum insulin-like growth factor I (IGF-I), insulin and glucose.
      The geometric mean values (+/- geometric S.D) of the relative absorption
      fractions were F5.9 IU/4 IU = AUC5.9 IU/AUC4 IU = (+/- 1.139) (P = 0.66), F11.7
      IU/AUC4 IU = AUC11.7 IU/AUC4 IU (1.14 +/- 1.21) (P = 0.009) AND F11.7 IU/5.9 IU =
      AUC11.7 IU/AUC5.9 IU = 1.12 (+/- 1.17) (P = 0.005), respectively. The 90%
      confidence intervals were contained within the limits of 0.80-1.25 accepted for
      bioequivalence. Geometric mean values (+/- geometric S.D.) of the relative
      observed maximum concentration, Cmax was for Cmax 5.9 IU/Cmax 4 IU = 1.04 (+/-
      1.19) (P = 0.32), Cmax 11.7 IU/Cmax 4 IU = 1.24 (+/- 1.21) (P = 0.0002) and Cmax
      11.7 IU/Cmax 5.9 IU = 1.19 (+/- 1.29) (P = 0.012). The median and the range
      values for the observed time to reach Cmax was tmax 5.9 IU/tmax 4 IU = 0.63 (0.04
      1.00), tmax 11.7 IU/tmax 4 IU = 0.59 (0.06-1.0) and tmax 11.7 IU/tmax 5.9 IU =
      0.90 (0.51-18.00). There were no significant differences in IGF-I, glucose and
      insulin profiles. Based on the upper limits of the 90% confidence intervals for
      relative AUC's the conclusion is that the three different preparations were
      bioequivalent.

PMID- 8884874
TI  - Effect of perinatal lead exposure on rat behaviour in open-field and two-way
      avoidance tasks.
AB  - In view of conflicting results in literature concerning lead exposure associated
      with behavioural alterations, this study investigated behaviour in the open-field
      and shuttle avoidance, for as well as tissue lead burdens of pre- and postnatally
      lead-exposed rats. Rats were exposed to the metal from conception to weaning by
      giving the dams 0.5, 2.0 or 4.0 mM lead acetate in drinking water. This regimen
      did not affect body weight gain of dams or offspring development and had no
      effect on cerebral weights nor on haematological parameters of 23-day-old rats.
      In 1-day-old rats, lead accumulated in the blood but not in the brain, whereas
      both in 23-day-old rats and in dams lead accumulated in blood, kidney and
      cerebral cortex. In the open-field, lead-exposed groups showed higher locomotor
      activity in the test session as compared to controls and did not show any
      decrease in rearing responses in the test, indicating less habituation. Lead
      treated rats subjected to a shuttle avoidance task showed no significant increase
      in avoidance responses between sessions as compared to control, indicating less
      retention. Moreover, only the control group presented a significant reduction of
      the footshock escape latency along testing session, suggesting a lead effect on
      footshock escape acquisition. In the shuttle box, intertrial crossing responses
      were not affected by lead treatment. The behavioural alterations occurred in
      animals with blood lead levels in the range 11-50.6 micrograms/dl.

PMID- 8884875
TI  - Effect of concomitant administration of clodronate and estramustine phosphate on
      their bioavailability in patients with metastasized prostate cancer.
AB  - Estramustine phosphate is generally used as a second-line treatment in patients
      with advanced prostate cancer. The bone metastases due to the cancer are often
      treated simultaneously with clodronate in order to relieve the bone pain.
      Therefore, the interaction of clodronate (800 mg orally four times daily) and
      estramustine phosphate (280 mg orally twice daily) on their bioavailability was
      studied in twelve patients with prostate carcinoma and bone metastases. The drugs
      were first given separately, each to six patients, for five days, and then
      concomitantly for the same period. The bioavailabilities of the drugs were
      calculated on the last day of each treatment period. When clodronate was given
      alone, its concentrations in serum and AUC for one dose interval (6 hr) did not
      differ from those obtained with the drug given concomitantly with estramustine
      phosphate, nor did the combination of estramustine phosphate change the excretion
      of clodronate in urine. The serum concentrations of estramustine phosphate were
      elevated by about 80% when the drug was given together with clodronate. The AUC
      for one dose interval (12 hr) was also significantly higher for estramustine
      phosphate with clodronate than without clodronate. The urinary excretion of
      estrone, a major metabolite of estramustine phosphate, was also significantly
      higher after the admission with clodronate. The results suggest that clodronate
      increases the oral bioavailability of estramustine phosphate.

PMID- 8884876
TI  - Characterisation of the melanocortin 4 receptor by radioligand binding.
AB  - The DNA encoding the human melanocortin 4 receptor was expressed in COS (CV-1
      origin, SV 40) cells and its radioligand binding properties was tested by using
      the [125I][Nle4, D-Phe7] alpha-melanocyte stimulating hormone (MSH). The
      radioligand was found to bind to a single saturable site with a Kd of 3.84 +/-
      0.57 nmol/l in the MC4 receptor expressing cells. The order of potency of a
      number of substance competing for the [125I][Nle4, D-Phe7] alpha-MSH binding was
      the following; [Nle4, D-Phe7] alpha-MSH > [Nle4]-alpha-MSH > beta-MSH > desacetyl
      alpha-MSH > alpha-MSH > ACTH (1-39) > ACTH (4-10) > gamma 1-MSH > gamma 2-MSH.
      This order of potency is unique for the melanocortin 4 receptor when compared to
      our previously published data for the other melanocortin receptor subtypes. Most
      notably the melanocortin 4 receptor shows highest affinity for beta-MSH, among
      the endogenous MSH-peptides. Furthermore the melanocortin 4 receptor shows very
      low affinity for the gamma-MSH peptides. This distinguishes the melanocortin 4
      receptor from the melanocortin 3 receptor, which is the other major central
      nervous system melanocortin-receptor, as melanocortin 3 receptor shows high
      affinity for gamma-MSH. Our finding might indicate a specific role for beta-MSH
      for the melanocortin 4 receptor.

PMID- 8884877
TI  - Eliprodil prevents expression of the 70 kDa heat shock protein in MK801-injured
      neurones.
AB  - The present study examined whether eliprodil (SL 82.0715), an N-methyl-D
      aspartate (NMDA) receptor antagonist acting on the polyamine sites induced
      expression of the 70 kDa heat shock protein (HSP70) in the rat brain. Whereas the
      NMDA channel blocker MK801 consistently induced HSP70 in posterior cingulate and
      retrosplenial cortices, eliprodil had no such effects even at the highest dose
      (50 mg/kg, intraperitoneally), supporting the idea that injury to the
      cerebrocortical neurones by NMDA receptor antagonists is probably related to
      specific sites of the receptor. Furthermore, eliprodil, given immediately after
      injection of MK801, blocked the effects of MK801 on HSP70. The result is
      discussed in terms of high affinity of eliprodil for the sigma receptor.

PMID- 8884878
TI  - Pharmacokinetics, metabolism and toxicity of the plant-derived photoxin alpha
      terthienyl.
AB  - The plant-derived insecticide, alpha-terthienyl was prepared by synthesis as
      3',4'-di[14C]-alpha-terthienyl for pharmacokinetic and metabolism studies. When
      administered orally to rats at a single dose of 50 mg/kg, excretion of the
      labelled material was maximal one day after administration and declined to no
      measurable quantities by day 4. Two metabolites [1,4-di(2'-thienyl)1,4-butadione
      and 2-2'-bithiophene-5-carboxylic acid] and trace quantities of the parent
      material were isolated from the urine and chemically identified. These represent
      the first metabolites of alpha-terthienyl identified. In pilot acute and subacute
      trials, unlabelled alpha-terthienyl was non-toxic when administered orally to
      rats as the "ready to use" formulation (0.1% active ingredient). The pure
      compound had an LD50 of 110 mg/kg when administered intraperitoneally to rats.
      The results suggest that there is considerable separation with respect to
      mosquito larvae and non-target mammal sensitivity.

PMID- 8884879
TI  - Screening of potential transport systems for methyl mercury uptake in rat
      erythrocytes at 5 degrees by use of inhibitors and substrates.
AB  - The current study was designed to screen the potential transport systems for
      methyl mercury (MeHg) uptake by isolated erythrocytes from rats at 5 degrees.
      Several inhibitors and substrates were used to test which potential transport
      system might be involved in MeHg uptake. Probenecid was used to test the organic
      anion transport system, valinomycin was used to test the effect of the membrane
      potential, D-glucose and cytochalasin B were used to test the facilitated
      diffusive D-glucose transport system and colchicine and vinblastine were used to
      test the microtubule system. The effects of Ca++, Mg++ and Na+ on MeHg uptake
      have been examined. Ouabain, ATP and glucose were used to test the active
      transport system, cysteine for the cysteine-facilitated transport system, glycine
      for system Gly, DL-methionine for system L, and MeHgCl and 4',4-diisothiocyano
      2',2-stilbenedisulfonic acid (DIDS) for the Cl- ion transport system. The results
      showed that MeHg uptake might be involved in the following transport systems at 5
      degrees: 1) organic anion transport system; 2) facilitated diffusive D-glucose
      transport system; 3) cysteine-facilitated transport system; 4) Cl- ion transport
      system. Moreover, the transport systems for MeHg uptake were sensitive to the
      membrane potential. Although the mechanisms of interaction of transport systems
      have not been fully clarified, evidence has been presented which support the
      existence of several simultaneous transport systems for MeHg uptake.

PMID- 8884880
TI  - Effect of chronic diazepam treatment on footshock-induced ultrasonic vocalization
      in adult male rats.
AB  - Rats were tested in the footshock-induced ultrasonic vocalization model of
      anxiety. The ultrasounds were recorded 1-11 min after 10 inescapable 0.6 mA
      footshocks each of 1 sec. duration. Repeated administration of benzodiazepines in
      the clinic has been reported to be accompanied by development of tolerance and
      withdrawal anxiety. The present study examined whether the ultrasonic
      vocalization model could reflect these two side effects. Diazepam 4.6 or 8.8
      mumol/ kg (1.3 or 2.5 mg/kg, subcutaneously) administered twice a day (8 a.m. and
      4 p.m.) abolished the vocalization after acute administration and after 3 weeks
      of treatment. Hence, no tolerance developed to the anxiolytic effect of diazepam.
      When the rats were tested 24 and 48 hr after the last doses of diazepam there
      were no significant differences from the control group, i.e. no apparent
      withdrawal anxiety. Instead, the control groups developed tolerance to the shock
      regimen during the chronic experiments. This was examined further by daily
      testing of a group of naive rats for 13 days. The findings indicated that there
      is a limitation in number of test sessions before tolerance to the model
      develops. In conclusion, the results of the present study contribute to the many
      contradictory and by no mean unequivocally findings in the literature. It
      indicates that substantial prediction of anxiolytic effects as well as unwanted
      side effects cannot be made from one single test model.

PMID- 8884881
TI  - Hepatocellular regeneration: key to thioacetamide autoprotection.
AB  - Low doses of thioacetamide stimulate cell division and tissue repair in the
      liver. The objective of this study was to develop an autoprotection model for
      thioacetamide and investigate if a low dose of thioacetamide (50 mg/kg orally)
      protects against lethality of a subsequently administered lethal dose (400 mg/kg
      orally) of the same compound. The extent of cell division was investigated to
      test if autoprotection results from augmented tissue repair and recovery from
      injury rather than decreased injury itself. After a single administration of the
      protective dose of thioacetamide, hepatocellular nuclear DNA synthesis as
      measured by 3H-thymidine incorporation into hepatocellular nuclear DNA peaked at
      36 hr indicating maximum level of S-phase stimulation. Pretreatment with the
      antimitotic colchicine abolished autoprotection and this was associated with a
      significantly decreased 3H-thymidine incorporation. Preadministration of the
      protective dose of thioacetamide did not result in an altered infliction of
      injury from the subsequently administered lethal dose. Colchicine intervention in
      the autoprotected group resulted in injury that followed a pattern similar to the
      group that received the high dose alone, ultimately resulting in animal death.
      These findings suggest that cell division stimulated by the protective low dose
      of thioacetamide is the critical mechanism in thioacetamide autoprotection.

PMID- 8884882
TI  - Quantitative and qualitative distribution of mercury in organs from arctic
      sledgedogs: an atomic absorption spectrophotometric and histochemical study of
      tissue samples from natural long-termed high dietary organic mercury-exposed dogs
      from Thule, Greenland.
AB  - Organs from 10 sledgedogs fed methyl mercury-containing organs and meat from
      predatory marine animals also eaten by humans in the Thule district of Greenland,
      were examined histochemically for cellular distribution of mercury, and the organ
      concentrations of mercury were quantified by atomic absorption spectrometry
      (total Hg). In selected organs the methyl mercuric level was determined by
      gaschromatography. The highest concentration of total mercury was found in
      mesenterial lymph nodes followed by liver and kidneys, which indicates that the
      lymphatic system might play an important role in the regulating transport of
      mercury to target organs. The concentrations were age-related, and the results
      suggest that demethylation takes place in all organs except skeletal muscles, but
      lowest in CNS. The distribution of mercury at cellular and subcellular levels was
      studied by the autometallographic technique. The atomic absorption spectrometric
      and autometallographic results were in good agreement. The brain mean
      concentration in the oldest group was 438 micrograms/kg, a level much lower than
      what has been reported to cause effects in the human central nervous system.
      However, if humans over a period of e.g. 50 years eat Arctic marine meat and
      accumulate mercury in the same way as dogs, the possibility that this may have
      health implications cannot be entirely excluded.

PMID- 8884883
TI  - Regional differences in cerebral noradrenaline turnover in mice withdrawn from
      repeated morphine treatment and tolerance to the effects of acute morphine.
AB  - The effects of morphine withdrawal and challenge doses (10 or 30 mg/kg) on the
      alpha-methyl-p-tyrosine (alpha MT)-induced noradrenaline (NA) depletion as well
      as on the free 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG) concentration
      were studied in various brain areas of NMRI mice. Morphine was given
      subcutaneously 3 times daily for 5 days followed by 1 or 3 days' withdrawal. In
      morphine withdrawn mice the alpha MT-induced NA depletion and the free MOPEG
      concentrations were differentially altered. At 1-day withdrawal the alpha MT
      induced NA depletion was retarded and the NA concentration was elevated in the
      forebrain area indicating reduced release of NA. Simultaneously, however, the
      free MOPEG concentration was significantly elevated in the forebrain area and in
      the lower brain stem suggesting enhanced NA turnover. No withdrawal-induced
      changes were found in the hypothalamic NA turnover. Acute morphine elevated the
      free MOPEG concentration and accelerated the alpha MT-induced NA depletion in all
      brain areas of control mice but not in mice withdrawn for 1 day from repeated
      morphine treatment. At 3 days' withdrawal, however, the 30 mg/kg morphine dose
      slightly accelerated the NA depletion in the forebrain area. These results show
      that morphine withdrawal differentially alters the alpha MT-induced NA depletion
      and the free MOPEG concentration in various mouse brain areas. These effects are
      relatively modest suggesting that in mice the noradrenergic mechanisms play a
      minor role in morphine withdrawal syndrome. However, in all brain areas of the
      morphine-withdrawn mice tolerance was found towards the NA turnover and release
      accelerating effect of acute morphine.

PMID- 8884884
TI  - Effects of selective opioid receptor antagonists on morphine-induced changes in
      striatal and limbic dopamine metabolism.
AB  - The effects of selective opioid receptor antagonists, beta-funaltrexamine
      (selective for mu receptor), naloxonazine (microliter) and naltrindole (delta) on
      morphine-induced changes in striatal and limbic dopamine (DA) metabolism were
      studied in rats. beta-Funaltrexamine (20 micrograms intracerebroventricularly)
      and naloxonazine (15 mg/kg intraperitoneally) were given 24 hr before morphine
      (15 mg/kg subcutaneously), and the rats were decapitated 60 min. after morphine.
      Naltrindole (1 mg/kg intraperitoneally) was given twice, 15 min. before and after
      morphine. Morphine significantly increased the concentrations of DA metabolites
      3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This effect
      was significantly antagonized by pretreatment with beta-funaltrexamine but not by
      naloxonazine or naltrindole. However, naloxonazine attenuated the antinociceptive
      effect of morphine in the hot-plate test. The concentration of DA was not
      significantly altered by any of the drugs studied. These results show that
      selective blockade of mu-opioid receptors totally blocks the increase of striatal
      and limbic DA metabolism induced by morphine. It seems that mu 2-subtype of mu
      opioid receptor predominantly mediates this effect. Blockade of delta-opioid
      receptor did not alter these effects of morphine.

PMID- 8884885
TI  - Effects of diabetes, insulin treatment, and osmolality on contractility of
      isolated rat resistance arteries.
AB  - The effects of osmolality, diabetes, and insulin-treatment on microvascular
      contractility were examined in mesenteric resistance arteries (internal diameter
      approximately 250 microns) isolated from streptozotocin-induced diabetic rats,
      streptozotocin-induced diabetic rats treated with 1-3 U insulin/day during the
      week before being killed, and age- and sex-matched control rats. Vessels were
      mounted in a microvascular myograph for isometric tension recording and responses
      were generated in physiological salt solutions with varying amounts of glucose or
      mannitol added. The passive response (expressed as the diameter the vessels would
      maintain if relaxed and exposed to a transmural pressure of 100 mmHg), the
      maximal response to noradrenaline, and the response produced by partial
      depolarization with 50 mmol/l potassium were not dependent on glucose or mannitol
      concentrations of the bathing medium; also, these responses were not dissimilar
      in vessels from the three groups of rats tested. The sensitivity to
      noradrenaline, however, was inversely related to the concentration of glucose (P
      < 0.01) and mannitol (P < 0.01) of the bathing medium without significant
      differences in slopes of regression lines between rat groups. Moreover, vessels
      from streptozotocin-induced diabetic rats were less sensitive to noradrenaline
      than were vessels from control rats; vessels from insulin-treated streptozotocin
      induced diabetic animals had the lowest sensitivity to noradrenaline. These data
      suggest that osmolality, diabetes, and insulin-treatment independently affect
      microvascular sensitivity to the endogenous neurotransmitter, noradrenaline.

PMID- 8884886
TI  - Prolonged oral treatment with two monoesters of meso-2,3-dimercaptosuccinic acid
      for depleting inorganic mercury retention in suckling rats.
AB  - Two monoesters of meso-2,3-dimercaptosuccinic acid (DMSA), monoisoamyl meso-2,3
      dimercaptosuccinate (Mi-ADMS) and mono-n-hexyl meso-2,3-dimercaptosuccinate (Mn
      HDMS) were compared to DMSA in their efficiency to mobilize 203Hg in mercury
      laden suckling rats. Seven-day-old pups were given 203Hg (18.5 kBq) with a dose
      of 0.5 mg Hg/kg/day as HgCl2 for five days. Seven days after the beginning of Hg
      loading a ten-day oral treatment with DMSA, Mi-ADMS, or Mn-HDMS was administered
      at a dose of 0.25 mmol/kg/day. At the end of experiment, radioactivity was
      measured in the whole body, liver, both kidneys, and brain. Monoesters of DMSA
      were superior to DMSA in decreasing body and organ Hg retention. The highest
      reduction in comparison to controls in groups treated with DMSA, Mi-ADMS, or Mn
      HDMS occurred in the kidneys (48%, 97%, and 96%), followed by reduction in the
      liver (24%, 84%, and 83%), and in the brain (8%, 23%, and 23%, respectively). For
      both, Mi-ADMS and Mn-HDMS, the reductions in the whole body and organs were
      significantly greater than in controls or DMSA-treated rats. No difference
      between the efficiency of the two DMSA-monoesters was found.

PMID- 8884887
TI  - Different postnatal development of convulsions and lethality induced by
      strychnine in rats.
AB  - The convulsant action of strychnine was studied in 310 male albino rats, aged 3
      to 25 days. Doses of 0.25-4 mg/kg were administered intraperitoneally and the
      animals were observed for 30 min. Generalized tonic-clonic seizures involving
      also tonic hindlimb extension occurred in all age groups. The convulsant effects
      of strychnine increased from day 3 to day 18, and decreased again from day 25, as
      indicated by the incidence and latencies of seizures. Lethal effects did not
      occur before day 12. Hyperactivity was seen as the first sign of strychnine
      action in rats during the first week of life, automatisms predominating in 18-day
      old animals. Electroencephalographic study in 30 rat pups with implanted
      electrodes demonstrated an extremely poor electro-clinical correlation.

PMID- 8884888
TI  - The effect of nicotine and its interaction with carbon tetrachloride in the rat
      liver.
AB  - In order to study the effects of nicotine on liver, groups of rats were given
      nicotine doses that simulated those seen in chronic smoking (54 and 108 mumol/l
      of nicotine) for 10 days. A subgroup was also given a single subcutaneous
      injection of 6 g/kg of carbon tetrachloride (CCl4) shortly before the animals of
      the group were killed. Histology demonstrated a significant hepatotoxic effect in
      the group receiving 108 mumol/l of nicotine when compared with the control group
      in the form of fatty change, focal or confluent necrosis and dark-cell change.
      The effects in pregnant rats were less severe. Carbon tetrachloride alone induced
      significant fatty change and focal necrosis in non-pregnant rats but not in
      pregnant rats. Nicotine also aggravated the CCl4 induced pathological changes in
      livers of both non-pregnant and pregnant animals. Thus nicotine alone, when given
      at a concentration of 108 mumol/l, exerted hepatotoxic effects; the alkaloid also
      aggravated the hepatotoxicity of CCl4. Pregnant rats were more resistant to the
      hepatotoxic effects produced by nicotine and CCl4.

PMID- 8884889
TI  - Action of reactive oxygen species and their antagonists on twitch tension of the
      rat phrenic nerve-diaphragm.
AB  - Reactive oxygen species have been implicated in normal and pathological processes
      of many tissues, including skeletal muscle. I extended previous studies by
      examining the effect of these intermediates and eight of their antagonists
      (superoxide dismutase, catalase, deferoxamine, [Cu(II)]2(3,5
      diisopropylsalicylate)4, 1,2-dimethyl-3-hydroxy-pyridone, 1,3-dimethyl-2
      thiourea, N-(2-mercaptopropionyl)-glycine, vitamin E) on indirectly stimulated
      twitch tension of an in vitro neuroskeletomuscular preparation, the phrenic nerve
      diaphragm of the rat. In the absence of exogenous reactive oxygen species, none
      of the antagonists potentiated twitch tension, and all but one (N-[2
      mercaptopropionyl]-glycine) of the membrane-permeant antagonists attenuated
      twitch tension. The reactive oxygen intermediate-generating system of purine plus
      xanthine oxidase reduced indirectly stimulated twitch tension by 36% while having
      no effect on directly stimulated twitch tension. Catalase (but not superoxide
      dismutase or deferoxamine) eliminated the reduction in twitch tension, indicating
      that hydrogen peroxide played a role in the reduction. The membrane-permeant
      antagonists [Cu(II)]2(3,5-diisopropylsalicylate)4 and 1,2-dimethyl-3-hydroxy
      pyridone also eliminated the reduction in twitch tension caused by reactive
      oxygen species, suggesting that hydrogen peroxide could have acted
      intracellularly through an iron-catalyzed Haber-Weiss reaction to produce
      hydroxyl radical, which in turn reacted with intracellular components, thereby
      reducing twitch tension.

PMID- 8884890
TI  - Effects of carbazochrome sodium sulfonate (AC-17) on oleic acid-induced lung
      injury.

PMID- 8884891
TI  - Phototoxicity due to sulphonamide derived oral antidiabetics and diuretics:
      investigations in a cell culture model.
AB  - A number of sulphonamide-derived oral antidiabetics (chlorpropamide,
      glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide) and
      diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothiazide,
      bumetanide, butizide, chloratalidone, furosemide, hydrochlorothiazide,
      hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and
      xipamide) were investigated for phototoxicity in a cell culture model. Cell death
      dependent on ultraviolet A fluence and test substance concentration was observed
      in the presence of the oral antidiabetics glibenclamide and gliquidone, as well
      as the diuretics bemetizide, bendroflumethiazide, benzyl-hydrochlorothiazide,
      bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide,
      polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at 5x10(
      5) M and higher concentrations, bemetizide, benzylhydrochlorothiazide, bumetanide
      and hydroflumethiazide were phototoxic at 2.5x10(-4) M and higher concentrations,
      and the oral antidiabetics glibenclamide and gliquidone as well as the diuretics
      butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide
      were phototoxic at 5(-4) M and higher concentrations. Electron microscopic
      investigations showed swelling of mitochondria and endoplasmic reticulum as well
      as aggregation of euchromatin when the cells were irradiated in the presence of
      photosensitizers.

PMID- 8884892
TI  - Chronic exposure of Sk-1 hairless mice to narrow-band ultraviolet A (320-355 nm)
AB  - Several recent investigations collectively suggest that the role of ultraviolet A
      (UVA) in chronic actinic skin damage may be greater than originally thought. In
      the present work, the output of a xenon-arc solar-simulator passed through a
      Bausch & Lomb monochromator in conjunction with a 2-mm Schott WG-320 filter
      produced narrow-band UVA centered at 338 nm, half-band width 24 nm, I0 = 3.4 +/-
      0.3 mW/cm2. We chronically irradiated 10 Sk-1 albino hairless mice 5 times per
      week for 18 weeks, starting with 1.25 J/cm2, for 33 irradiation days,
      sequentially followed by 1.50 J/cm2 (34 days), 1.8 J/cm2 (10 days), 2.0 J/cm2 (22
      days) to afford a total UVA dose of 154.3 J/cm2 over 99 irradiation days.
      Erythema was noted clinically by day 6, which persisted throughout the
      irradiation. During the irradiation period, some scaling, consistent with mild
      epidermal hyperplasia was noted during irradiation days 37-56. This response
      later regressed despite continued chronic irradiation. Hematoxylin and eosin
      examination immediately after the final irradiation revealed a mild inflammatory
      response, with some dermal restructuring. At the end of the experiment, no
      significant signs of epidermal hyperplasia or (pre)malignant lesions were seen,
      although some stratum corneum thickening was noted. Marked dermal collagen damage
      and moderate elastosis was also evident. We believe that the observed differences
      in results reported in previous studies are in large part due to differences in
      light sources and irradiation protocols.

PMID- 8884893
TI  - Survey of the variation in ultraviolet outputs from ultraviolet A sunbeds in
      Bradford.
AB  - Concerns have been expressed for some time regarding the growth of the cosmetic
      suntanning industry and the potential harmful effects resulting from these
      exposures. Recently published work has appeared to confirm a link between sunbed
      use and skin cancer. A previous survey in Oxford some years ago demonstrated
      significant output variations, and we have attempted to extend and update that
      work. Ultraviolet A, UVB and blue-light output measurements were made on 50
      sunbeds using a radiometer fitted with broad-band filters and detectors. A number
      of irradiance measurements were made on each sunbed within each waveband so that
      the uniformity of the output could also be assessed. UVA outputs varied by a
      factor of 3, with a mean of 13.5 mW/cm2; UVB outputs varied by a factor of 60,
      with a mean of 19.2 microW/cm2; and blue-light outputs varied by a factor of 2.5,
      with a mean of 2.5 mW/cm2. Outputs fall on average to 80% of the central value at
      either end of the sunbed. Facial units in sunbeds ranged in output between 18 and
      45 mW/cm2. Output uniformity shows wide variation, with 16% of the sunbeds having
      an axial coefficient of variation > 10%. UVB output is highly tube-specific.
      Eyewear used in sunbeds should also protect against blue light.

PMID- 8884894
TI  - Interleukin-15 expression by human endothelial cells: up-regulation by
      ultraviolet B and psoralen plus ultraviolet A treatment.
AB  - The purposes of the present study were to determine whether endothelial cells
      express IL-15 and to evaluate effects of ultraviolet B (UVB) and 8
      methoxypsoralens plus UVA (PUVA) on such expression. Cultured human endothelial
      cells derived from dermis or umbilical veins were subjected to reverse
      transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analyses for the
      detection of IL-15 mRNA and protein, respectively. Both dermal and umbilical vein
      endothelial cells were shown to express IL-15 mRNA and protein, and these markers
      were upregulated following UVB or PUVA treatment (but not by UVA or 8
      methoxypsoralens alone). Also using RT-PCR, dermal and umbilical vein endothelial
      cells were shown to express IL-2R gamma c mRNA. These results expand the sources
      of IL-15 in skin to include keratinocytes, dermal fibroblasts, and now
      endothelial cells. That IL-15 from all three skin cells can be upregulated by UV
      treatment suggests a role for this cytokine in photosensitive disorders. Finally,
      the possibility of an autocrine effect of IL-15 on endothelial cells is raised by
      the expression of IL-2R gamma c in these cells.

PMID- 8884895
TI  - Higher cyclobutane pyrimidine dimer and (6-4) photoproduct yields in epidermis of
      normal humans with increased sensitivity to ultraviolet B radiation.
AB  - Cyclobutane pyrimidine dimer (CPD) and (6-4) photoproduct induced in the
      epidermis of five Japanese volunteers exposed to ultraviolet (UVB) radiation were
      measured with monoclonal antibodies specific for each photoproduct. The
      volunteers comprised two individuals who are sensitive to solar irradiation (low
      minimal erythema dose [MED]) and three who are less sensitive. The yields of CPD
      and (6-4) photoproduct were within similar ranges after 1 MED or 3 MED doses. The
      yields of both photoproducts after the same dose of irradiation (120 mJ/cm2) were
      higher in UV-sensitive individuals than in less sensitive individuals. By 24 h
      after irradiation, an average of 60% of CPD had been removed after the 1 MED
      dose, 27% after the 3 MED dose and 34% after 120 mJ/cm2. The (6-4) photoproduct
      was removed within 24 h, independently of the dose of UVB tested. These data
      suggest that DNA photoproducts participate in initiating UVB-induced erythema,
      and partially explain why individuals with higher sensitivity to UVB have a
      higher risk of UV-induced skin cancer.

PMID- 8884896
TI  - A double-blind, placebo-controlled, crossover trial of oral vitamin C in
      erythropoietic protoporphyria.
AB  - There is evidence that reactive oxygen species and free radicals may be involved
      in the pathogenesis of photosensitivity in erythropoietic protoporphyria (EPP).
      Considering the well-known antioxidant properties of vitamin C, we investigated
      whether oral supplementation with this vitamin was photoprotective in patients
      with EPP. Twelve patients with EPP received either oral vitamin C 1 g daily or
      placebo, for 4 weeks, followed by a crossover period of another 4 weeks. Nine
      patients were already receiving beta carotene at entry and continued this at the
      same dose throughout the study. Patients compared their sunlight tolerance
      throughout each of the treatment periods with sunlight tolerance at entry on a 10
      cm visual analogue scale; at the end of the study, they were asked to choose
      which treatment period they felt had been associated with least photosensitivity.
      Eight patients stated that they were able to tolerate sunshine better during the
      vitamin C period, 2 during the placebo period and 2 noticed no difference between
      the two periods. This distribution of preferences approached but did not reach
      statistical significance in favour of vitamin C. Visual analogue scores improved
      by a median of 1.2 cm in the vitamin C period. This change too approached but did
      not reach statistical significance. Although these results do not reach
      statistical significance, it appears possible that oral vitamin C may reduce
      photosensitivity in some patients with EPP. A larger study is necessary to
      confirm this impression.

PMID- 8884897
TI  - Porphyrin metabolism in hepatitis C infection.
AB  - Hepatitis C virus has been implicated as a major precipitating factor in
      porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone
      is sufficient to induce PCT, we screened two groups of patients with hepatitis C
      infection. The first group comprised women who had become HCV positive secondary
      to immunization with anti-D immunoglobulin (group 1). Group 2 included males and
      females who were HCV positive but HIV negative secondary to intravenous drug
      abuse. Though both groups had very abnormal liver function tests, we found no
      significant abnormalities in porphyrin metabolism in these groups of patients.
      Therefore, in this study population, we conclude that HCV infection alone is
      insufficient to cause porphyrin metabolic derangement.

PMID- 8884898
TI  - Perturbation effects in dosimetry: Part I. Kilovoltage x-rays and electrons.
AB  - Perturbation effects are defined as departures from ideal large-detector or Bragg
      Gray cavity behaviour. Such effects are central to the use of practical
      dosimeters for accurate dose determination, as is required in external-beam
      radiotherapy. A theoretical framework for treating perturbation effects is
      established. In this first part of the review, perturbation in kilovoltage x-ray
      and megavoltage electron beams are treated in detail, with the emphasis on
      ionization chambers. The displacement factor for ion chambers in kilovoltage x
      ray beams is discussed, starting with the early, pioneering work of Lamerton and
      Liden. The evidence for the large values of the perturbation factor in medium
      energy x-ray beams (between 100 and 300 kV) recommended in the 1987 IAEA
      dosimetry code is critically examined and revised, smaller values are given. In
      electron beams the theoretical approaches to the correction for the in-scattering
      correction in gas-filled cavities is discussed in detail. The evidence for
      negligible perturbation in low-energy electron beams in plane-parallel chambers
      with adequate guardring widths is critically reviewed, including the suggested
      correction for perturbation due to backscattering differences between the chamber
      wall material and the medium. The various models for the response of
      thermoluminescent dosimeters in electron beams are discussed. It is concluded
      that Monte Carlo simulation of dosimeter response is likely to play an even
      bigger role in the future.

PMID- 8884899
TI  - Photon beams for radiosurgery produced by laser Compton backscattering from
      relativistic electrons.
AB  - The frontal collisions of a laser beam with relativistic electrons result in
      Compton-backscattered photons. The energy of these photons is dependent on the
      laser and electron energy in the range from kilo-electron-volts to tens of mega
      electron-volts. In a sufficiently narrow backscattering angle the photons are
      nearly monochromatic. Over the past 30 years there have been several attempts to
      produce photon beams by laser backscattering from relativistic electrons stored
      in magnetic ring structures. One aim is to produce photons in the high mega
      electron-volt energy range with fluxes useful for nuclear physics research;
      another is to produce photons in the high kilo-electron-volt energy range, which
      would be useful for medical applications, such as coronary angiography or
      treatment of tumour. Our present interest is to investigate the possibility of
      using 34 keV to 10 MeV photon beams for applications in stereotactic functional
      radiosurgery. We foresee the possibility of neurosurgical operations through the
      intact skull with precise and effective destruction of deeply lying millimetre
      sized targets with minimal effects on intervening structures, high
      reproducibility and good prediction of the results. Our paper presents: a Monte
      Carlo study of radiosurgery based on cross firing with 34 keV to 100 MeV photon
      beams and 200 and 580 MeV proton beams, a theoretical description of the
      kinematics of Compton backscattering and estimates of the backscattered photon
      flux from several combinations of laser cavities at Nd:YAG (1.17 eV) and CO2
      (0.117 eV) laser energies and electron storage rings energies in the range 0.1
      1.3 GeV. As examples, existing magnetic structures, such as the DA phi NE
      Accumulator in the lower energy range and the Trieste Synchrotron Light Source
      ELETTRA in the higher energy range have been utilized in the calculations. The
      Monte Carlo study has shown that radiosurgery with photon beams of energies in
      mega-electron-volt energy range enables precise destruction of deeply lying
      millimetre-sized targets with minimal effects on intervening structures. Its
      precision is comparable to that of radiosurgery with 200-580 MeV proton beam, but
      our hope is that radiosurgery with lower energy photon beams could be more
      precise and less expensive. An average dose of 200 Gy can be delivered to a
      target of diameter 2 mm at the centre of an 18 cm diameter phantom in 1 h using
      photon beams of fluences 7.3 x 10(10), 1.8 x 10(10), 6.5 x 10(8), 2.2 x 10(8),
      8.6 x 10(7) and 7.8 x 10(6) photons per second at 34 keV, 100 keV, 1 MeV, 3 MeV,
      10 MeV and 100 MeV per cross section of beam of 2 mm diameter, respectively. 34
      100 keV photon beams were studied in the hope of finding a strong enhancement of
      their efficiency if a stable high-Z element were to be introduced into the
      target's DNA. It is shown that, with a low-energy ring running at about 0.4 GeV
      and a Nd:YAG laser, it would be possible to obtain the required 3 MeV photon beam
      flux to deliver the average dose within 1 h, assuming an average distance between
      the source and the target of about 5 m. With a similar machine used at about 1.3
      GeV and a CO2 laser, a 3 MeV photon beam is obtained and the exposure time can be
      reduced to less than 1 min, assuming a roughly 10 m distance between source and
      target (here a beam angle of 0.1 mrad only had to be considered due to the larger
      angular energy and yield spread). With a lower electron energy of 138 MeV and a
      CO2 laser, a 34 keV photon beam can be produced. More than 45 h would be needed
      to deliver the same dose. We hope that this time could be shortened considerably
      if stable iodine were introduced into the target with the help of a DNA-seeking
      molecular carrier. In this case the geometrical precision would be further
      improved.

PMID- 8884900
TI  - Analyses of multi-irradiation film for system alignments in stereotactic
      radiotherapy (SRT) and radiosurgery (SRS).
AB  - In stereotactic radiosurgery, a seven-irradiation film was used to define any
      discrepancy between the beam and target centres. A mathematical model based on
      the linac alignment and target set-up was developed to diagnose the discrepancies
      of the seven-irradiation film between the beam and simulation target centres.
      From the measured data of the multi-irradiation film, this mathematical model
      leads to five parameters in seven equations. Twin computer codes were employed to
      solve the five parameters from the seven equations. By feeding the discrepancy
      data into the two computer codes, the sources of the target-to-beam discrepancy
      were revealed. From these decoded sources, the target coordinates were adjusted
      and then the seven-irradiation film procedure was repeated. This discrepancy thus
      obtained was found to be drastically reduced. Some decoded parameters were
      consistently verified by direct measurements. This demonstrates that the present
      mathematical model and computer code do reveal the causes of the target-to-beam
      misalignment and gantry sag. In a further effort to test the feasibility of the
      mathematical model and the computer codes, the target's lateral coordinate was
      deliberately offset by 1.5 mm and then another seven-irradiation film was taken.
      By inserting these discrepancies into the computer codes, it was found that the
      deviation was consistent with the intentional offset. In addition, the
      mathematical model and computer codes are applicable to any multi-irradiation
      technique.

PMID- 8884901
TI  - Optimized target localization in stereotactic radiosurgery using real-time
      digital portal images.
AB  - This paper presents a method for optimized estimation of target localization in
      stereotactic radiosurgery using real-time digital portal images. The positions of
      the two radiation sources and the two projection planes in radiosurgery can be
      chosen arbitrarily. The reconstruction of the target is characterized as a non
      linear multi-variable optimization problem, which minimizes the difference
      between the actual target and the reconstructed target. This optimization problem
      is solved by the Gaussian least square differential correction (GLSDC) method.
      Due to the digitized errors and input data errors, the algorithm defines an
      indirect reference factor (the shortest distance between two x-rays pointing onto
      the target) as an indication of the accuracy of the method. Our experimental
      results show that the reference factor is less than 1.0 mm for the correct data
      entry. The proposed algorithm provides a method that supports on-line target
      localization which can be done directly on the digital portal imaging device.

PMID- 8884902
TI  - Contribution from the inner shell of water vapour to dose profiles under proton
      and alpha particle irradiation.
AB  - Doubly differential cross sections for electron emission calculated using the CDW
      EIS model and a simple approximation for the electron transport in the target are
      used to obtain dose profiles around the ion path for proton and alpha particles
      in water vapour. The contribution from each initial molecular orbital is
      determined. At large distances from the track, discrepancies are found with other
      models and with the well known r-2 dependence.

PMID- 8884903
TI  - The influence of the beam modulation technique on dose and RBE in proton
      radiation therapy.
AB  - Because a dose can be described as fluence times LET, it is evident that, in a
      mixed radiation field, similar doses can be achieved with different particle
      energy distributions. Isodose contours are iso-effect contours only if the energy
      spectra of the accompanying particles remain constant. Under this condition, the
      beam delivery technique used to build a spread-out Bragg peak (SOBP) can
      influence the relative biological effectiveness (RBE). We investigated the
      influence of the beam modulation method on the dose distribution and, taking into
      account the respective RBEs, on the biological dose distribution. For this, we
      first performed proton transport calculations in order to obtain the dose and the
      proton energy spectra at a given depth. Secondly, RBE values were calculated
      using the microdosimetric response function and the track structure model for two
      biological end points. We found an increasing RBE with depth within the SOBP. The
      higher the energy used for modulation the lower the average LET and the RBE and
      the higher the proton fluence. The RBE for an active beam modulation system
      behaves like the respective RBE of a passive system with similar initial beam
      energy.

PMID- 8884904
TI  - Response analysis of TLD-300 dosimeters in heavy-particle beams.
AB  - In vivo dosimetry is recommended as part of the quality control procedure for
      treatment verification in radiation therapy. Using thermoluminescence, such
      controls are planned in the p(65) + Be neutron and 85 MeV proton beams produced
      at the cyclotron at Louvain-La-Neuve and dedicated to therapy applications. A
      preliminary study of the peak 3 (150 degrees C) and peak 5 (250 degrees C)
      response of CaF2:Tm (TLD-300) to neutron and proton beams aimed to analyse the
      effect of different radiation qualities on the dosimetric behaviour of the
      detector irradiated in phantom. To broaden the range of investigation, the study
      was extended to an experimental 12C heavy ion beam (95 MeV/nucleon). The peak 3
      and 5 sensitivities in the neutron beam, compared to 60Co, varied little with
      depth. A major change of peak 5 sensitivity was observed for samples positioned
      under five leaves of the multi-leaf collimator. While peak 3 sensitivity was
      constant with depth in the unmodulated proton beam, peak 5 sensitivity increased
      by 15%. Near the Bragg peak, peak 3 showed the highest decrease of sensitivity.
      In the modulated proton beam, the sensitivity values were not significantly
      smaller than those measured in the unmodulated beam far from the Bragg peak
      region. The ratio of the heights of peak 3 and peak 5 decreased by 70% from the
      60Co reference radiation to the 12C heavy-ion beam. This parameter was strongly
      correlated with the change of radiation quality.

PMID- 8884905
TI  - A new method for optimum dose distribution determination taking tumour mobility
      into account.
AB  - A method for determining the optimum dose distribution in the planning target
      volume is proposed when target volumes are deliberately enlarged to account for
      tumour mobility in external beam radiotherapy. The optimum dose distribution is a
      dose distribution that will result in an acceptable level of tumour control
      probability (TCP) in most of the arising cases of tumour dislocation. An
      assumption is made that the possible shifts of the tumour are subject to a
      Gaussian distribution with mean zero and known variance. The idea of a reduced
      (mean in ensemble) tumour cell density is introduced. On this basis, the target
      volume and dose distribution in it are determined. The tumour control probability
      as a function of the shift of the tumour has been calculated. The Monte Carlo
      method has been used to simulate TCP distributions corresponding to tumour
      mobility characterized by different variances. The obtained TCP distributions are
      independent of the variance of the mobility because the dose distribution in the
      planning target volume is prescribed so that the mobility variance is taken into
      account. For simplicity a one-dimensional model is used but three-dimensional
      generalization can be done.

PMID- 8884906
TI  - Implementation of the Varian EDW into a commercial RTP system.
AB  - An enhanced dynamic wedge system (EDW) has been installed onto our Clinac 600C (6
      MV) linear accelerator. This paper addresses and describes the measurements taken
      and subsequent analysis required to enable the planning of EDW using our
      commercial radiotherapy treatment planning (RTP) system. This implementation into
      a 'closed' commercial system is performed without the use of specialized
      measurement equipment or the necessity of introducing new calculation algorithms
      and is therefore independent of the RTP manufacturer. We consider that, for
      incorporation of techniques such as EDW into routine clinical use, a simple
      verifiable method of inclusion into the RTP system must be achieved. This paper
      also presents a methodology for quality control of dynamic fields chosen for
      clinical use which is quick and easy to use by virtue of its use of film
      dosimetry. We present the method of film calibration used in this work.

PMID- 8884907
TI  - Reconstruction of two-dimensional current distribution from tangential MCG
      measurement.
AB  - We describe a two-dimensional reconstruction method for tangential
      magnetocardiograms (MCGs). This method is based on two-dimensional Fourier
      analysis, and we used a new type of window function for tangential MCG to solve
      the problem of the small number of measurement points. By using this method,
      cardiac activity can be estimated as a two-dimensional current distribution. To
      determine the effectiveness of this method, we measured tangential MCGs of normal
      subjects, and compared the estimated current distribution with the actual cardiac
      muscle activity. Using this method, we were able to clearly show cardiac
      activity.

PMID- 8884908
TI  - Niobium/molybdenum K-edge filtration in mammography: contrast and dose
      evaluation.
AB  - The use of a dual K-edge filter (niobium-molybdenum) with a Mo anode x-ray tube
      for application to mammography is investigated. The incident and transmitted
      energy spectral distributions are compared with those provided by a molybdenum
      anode molybdenum filter tube (standard source). The imaging characteristics in
      terms of contrast and mean glandular dose have been evaluated for various phantom
      thicknesses. The niobium filtration removes the molybdenum K beta line almost
      completely from the beam spectrum whereas a Mo filtration is needed to avoid the
      increases both in the low-energy component of the incident beam and in the higher
      energy component of the transmitted one. The contrast is improved with respect to
      the standard source and the mean glandular dose is only slightly increased for
      moderate transmission phantoms (thickness 2-4 cm).

PMID- 8884909
TI  - Computed tomography using algebraic reconstruction techniques (ARTs) with
      different projection access schemes: a comparison study under practical
      situations.
AB  - In a previous report we presented a novel ART technique with the projections
      arranged and accessed in a multilevel scheme (MLS) for efficient algebraic image
      reconstruction, but whether the scheme is still superior in real situations where
      the data are noisy is unknown. In this paper, we make a detailed comparison
      between MLS and the other two conventional projection access orderings in ART:
      the random permutation scheme (RPS) and the sequential access scheme (SAS). By
      simulating reconstructions of a human head using different sizes of detector,
      taking different numbers of projections, each measurement under a different
      number of photons, a full mapping of the reconstruction accuracy measured by
      correlation coefficient for the three schemes has been made. Test results
      demonstrate that one-iteration MLS produces the best reconstruction in many
      situations. It outperforms one-iteration RPS when the noise level is low. SAS in
      many cases can never attain the image quality of one-iteration MLS, even with
      many more iterations. A convergence test using different initial guesses also
      demonstrates that MLS has less initial dependence. In the Fourier domain, it also
      represents an efficient and fast implementation of the Fourier slice theorem.

PMID- 8884910
TI  - A method for determining the diffusion coefficient in Fe(II/III) radiation
      dosimetry gels using finite elements.
AB  - Magnetic resonance imaging (MRI) may be used to image three-dimensional dose
      distributions of ionizing radiation in tissue equivalent gels infused with
      ferrous sulphate solutions, commonly known as Fricke gels. In this technique,
      ferrous (Fe2+) ions are oxidized to ferric (Fe3+) ions by free radicals produced
      by ionizing radiation. A limitation on this technique is the diffusion of ferric
      (Fe3+) ions in the gel. A method is presented for evaluating the diffusion
      coefficient in Fricke gels. Finite elements are used to model variations of the
      concentration in space, coupled with an analytical scheme to integrate the
      resulting system of equations through time. This method may be used for problems
      with one, two or three space dimensions and with arbitrary initial and boundary
      conditions. Results are presented for one- and two-dimensional data.

PMID- 8884911
TI  - Optimization of noise-equivalent count rates in 3D PET.
AB  - We have used noise-equivalent count (NEC) rates to optimize count rate
      performance for 3D acquisition in PET in a wide range of situations, with
      particular reference to imaging of the torso. We have also compared NEC
      performance for 2D and 3D acquisition in order to establish the conditions under
      which 3D mode offers an improvement over 2D mode. Measurements were performed on
      four tissue-equivalent phantoms ranging in size from that of an infant's head (13
      cm diameter) to that of an obese adult's chest (37 cm x 48 cm). Count rate data
      were acquired as a function of phantom size, activity in the field of view, lower
      energy discriminator level (LLD) and acquisition mode, and NEC rates were derived
      as a function of these variables. The LLD at which the highest NEC rate is
      obtained shows a dependence both on phantom size and on the activity in the field
      of view both for 2D and for 3D acquisition. The relative advantage of 3D mode
      over 2D mode, at the optimum LLD setting, is also strongly dependent both on
      activity in the field of view (FOV) and on the phantom size. The main limiting
      factors for 3D NEC rates are detector dead-time for small phantoms and random
      coincidences for large phantoms. The 3D NEC rate is more than twice as great as
      the 2D NEC rate when less than 60 MBq is present in the FOV for all phantoms
      except the largest, in which case a ratio of two is only achieved for activities
      less than 25 MBq. For the smallest phantom, 3D/2D NEC ratios of greater than 3.5
      are obtained when the activity in the FOV falls below 10 MBq.

PMID- 8884912
TI  - Bayesian reconstruction of PET images: methodology and performance analysis.
AB  - We describe a practical statistical methodology for the reconstruction of PET
      images. Our approach is based on a Bayesian formulation of the imaging problem.
      The data are modelled as independent Poisson random variables and the image is
      modelled using a Markov random field smoothing prior. We describe a sequence of
      calibration procedures which are performed before reconstruction: (i) calculation
      of accurate attenuation correction factors from re-projected Bayesian
      reconstructions of the transmission image; (ii) estimation of the mean of the
      randoms component in the data; and (iii) computation of the scatter component in
      the data using a Klein-Nishina-based scatter estimation method. The Bayesian
      estimate of the PET image is then reconstructed using a pre-conditioned conjugate
      gradient method. We performed a quantitation study with a multi-compartment chest
      phantom in a Siemens/CTI ECAT931 system. Using 40 1 min frames, we computed the
      ensemble mean and variance over several regions of interest from images
      reconstructed using the Bayesian and a standard filtered backprojection (FBP)
      protocol. The values for the region of interest were compared with well counter
      data for each compartment. These results show that the Bayesian protocol can
      produce substantial improvements in relative quantitation over the standard FBP
      protocol, particularly when short transmission scans are used. An example showing
      the application of the method to a clinical chest study is also given.

PMID- 8884913
TI  - Application of a new discreet form of Gauss' theorem for measuring volume.
AB  - Volume measurements are useful in many branches of science and medicine. They are
      usually accomplished by acquiring a sequence of cross sectional images through
      the object using an appropriate scanning modality, for example x-ray computed
      tomography (CT), magnetic resonance (MR) or ultrasound (US). In the cases of CT
      and MR, a dividing cubes algorithm can be used to describe the surface as a
      triangle mesh. However, such algorithms are not suitable for US data, especially
      when the image sequence is multiplanar (as it usually is). This problem may be
      overcome by manually tracing regions of interest (ROIs) on the registered
      multiplanar images and connecting the points into a triangular mesh. In this
      paper we describe and evaluate a new discreet form of Gauss' theorem which
      enables the calculation of the volume of any enclosed surface described by a
      triangular mesh. The volume is calculated by summing the vector product of the
      centroid, area and normal of each surface triangle. The algorithm was tested on
      computer-generated objects, US-scanned balloons, livers and kidneys and CT
      scanned clay rocks. The results, expressed as the mean percentage difference +/-
      one standard deviation were 1.2 +/- 2.3, 5.5 +/- 4.7, 3.0 +/- 3.2 and -1.2 +/-
      3.2% for balloons, livers, kidneys and rocks respectively. The results compare
      favourably with other volume estimation methods such as planimetry and
      tetrahedral decomposition.

PMID- 8884914
TI  - Preparation of solid phantoms with defined scattering and absorption properties
      for optical tomography.
AB  - We have developed diffusely scattering solid phantoms with optical (scattering)
      properties amenable to theoretical calculations. Monodisperse quartz glass
      spheres were used as scatterers embedded in polyester resin. An infrared dye was
      added to simulate absorption by biological tissue. Solid phantoms were tested for
      their macroscopic homogeneity. Several phantoms were built with well-defined
      spatial variations in their transport scattering and absorption coefficients to
      be used for optical tomography. Scattering, transport scattering, and absorption
      coefficients of solid, homogeneous phantoms and of aqueous suspensions of
      monodisperse quartz glass spheres were derived from measurements of time
      integrated collimated transmittance and time-resolved diffuse transmittance. For
      aqueous suspensions of monodisperse quartz glass spheres at known number density
      scattering and transport scattering coefficients calculated by Mie theory are in
      quantitative agreement with experimentally derived values. In addition, diffuse
      reflectance and diffuse transmittance of aqueous suspensions at various number
      densities were measured and found to be in excellent agreement with results of
      Monte Carlo calculations using theoretical values for the scattering coefficients
      and anisotropy parameters.

PMID- 8884915
TI  - Cellular dosimetry of diagnostic radionuclides for spherical and ellipsoidal
      geometry.
AB  - Radionuclides which emit Auger electrons are widely used in diagnostic nuclear
      medicine. Studies have shown possible uptake of these in developing germ cells
      within the testes. In addition, mature sperm within the reproductive tract may be
      subject to uptake of radionuclides from the circulating blood pool. Though much
      work has been carried out concerning cellular dosimetry applied to spherical
      sources, such an approach may lead to significant errors when considering
      spermatids and spermatozoa, which are almost ellipsoidal in shape (with the long
      axis twice the short). A numerical method for determining geometrical reduction
      factors has been developed and used in conjunction with experimentally determined
      range-energy relationships for electrons, to determine dose gradients and S
      factors for homogeneous distributions of four commonly used diagnostic
      radionuclides (99mTc, 111In, 123I and 201Tl) throughout source regions of both
      spherical and ellipsoidal geometry at typical cellular dimensions. The results
      indicate that assumption of spherical geometry is acceptable when determining S
      factors for late-type germ cells, but introduces error into calculations of dose
      distribution towards the edge of the cell.

PMID- 8884916
TI  - Evaluation of a technique for simulation of gamma camera images.
AB  - Simulation of the gamma camera imaging process has applications in radionuclide
      imaging in image formation, interpretation and evaluation. Current algorithms are
      hindered by the length of time taken to perform accurate simulation. In this
      study an algorithm is developed which uses a number of simplifying approximations
      to improve speed of operation: restriction of the extent of the primary and
      scatter point spread functions, coarse sampling of the PSFs in the direction
      perpendicular to the camera face and use of a circularly symmetric scatter
      function. The effect of these approximations is assessed qualitatively and
      quantitatively by comparing simulations with corresponding real measurements. The
      application of the technique to clinical images using magnetic resonance data is
      demonstrated. The results show that improvements in speed of about a factor of
      ten may be achieved at the expense of minimal loss of accuracy. The algorithm
      should prove useful in speeding up applications of simulation.

PMID- 8884917
TI  - Use of low-frequency electrical impedance measurements to determine phospholipid
      content in amniotic fluid.
AB  - In this report we propose a new method for an in vitro test of the foetal lung
      maturity based on the measurement of the electrical conductivity of the overall
      amniotic fluid obtained from transabdominal amniocentesis, since this quantity
      can be linked to a first approximation in a very simple way to the phospholipid
      content. We have carried out measurements of 85 different samples of amniotic
      fluid as a function of gestation weeks and we have observed a pronounced change
      of the electrical conductivity that reflects the increase in the phospholipid
      concentration occurring at the end of normal pregnancies. The method could be
      further developed to obtain similar information on in vivo experiments by means
      of bioelectric impedance tomography, taking advantage of the frequency dependence
      of the tissue electrical impedance.

PMID- 8884918
TI  - Can sensory neurones in culture serve as a model of nociception?
AB  - Nociceptors belong to A delta and C afferents that are equipped in the periphery
      with receptors for detecting potentially damaging physical and chemical stimuli.
      This review summarizes experimental evidence that these receptors represented by
      ionic channels are also functionally expressed on the cell bodies of sensory
      neurones in short-term cultures. The nociceptors belong predominantly to the
      small and medium size DRG neurones in which algogens such as weak acids,
      capsaicin, bradykinin and scrotonin produce inward currents that can generate
      impulse activity. It seems likely that the neurones which are not sensitive to
      algogens but to GABA, ATP or glutamate, agents not producing pain in humans,
      belong to other categories of DRG neurones equipped for detecting other
      modalities of sensation. new techniques for physical stimulation of DRG neurones
      in culture may be of great help in the search for complementing the criteria for
      distinguishing nociceptors among other neurones in culture. It is suggested that
      such an in vitro model will be useful for studying cellular mechanisms of
      nociception.

PMID- 8884919
TI  - Changes of extracellular space volume and tortuosity in the spinal cord of Lewis
      rats with experimental autoimmune encephalomyelitis.
AB  - Three diffusion parameters of nervous tissue, extracellular space (ECS) volume
      fraction (alpha), tortuosity (gamma) and non-specific uptake (k') of
      tetramethylammonium (TMA+), were studied in the spinal cord of rats during
      experimental autoimmune encephalomyelitis (EAE). The three parameters were
      determined in vivo from concentration-time profiles of TMA+ using ion-selective
      microelectrodes. EAE was induced by injection of guinea-pig myelin basic protein
      (MBP), which resulted in typical morphological changes in the CNS tissue, namely
      inflammatory reaction, astrogliosis, blood-brain barrier (BBB) damage and
      paralysis. EAE was accompanied by a statistically significant increase of alpha
      (mean +/- S.E.M.) in the dorsal horn from 0.21 +/- 0.01 to 0.28 +/- 0.02, in the
      intermediate region from 0.22 +/- 0.01 to 0.33 +/- 0.02, in the ventral horn from
      0.23 +/- 0.01 to 0.47 +/- 0.02 and in white matter from 0.18 +/- 0.03 to 0.30 +/-
      0.03. There were significant decreases in tortuosity in the dorsal horn and in
      the intermediate region and decreases in non-specific uptake in the intermediate
      region and in the ventral horn. Although the inflammatory reaction and the
      astrogliosis preceded and greatly outlasted the neurological symptoms, the BBB
      damage had a similar time course. Moreover, there was a close correlation between
      the changes in extracellular space diffusion parameters and the manifestation of
      neurological signs. We suggest that the expansion of the extracellular space
      alters the diffusion properties in the spinal cord. This may affect synaptic as
      well as non-synaptic transmission, intercellular communication and recovery from
      acute EAE, and may contribute to the manifestation of neurological signs in EAE
      rats.

PMID- 8884920
TI  - Lymphatic bioavailability of diazepam and desmethyldiazepam in the rat.
AB  - The lymphatic bioavailability (FL) of diazepam (DZ) and its major metabolite
      desmethyldiazepam (DDZ) was studied. DZ was administered in intravenous and
      intraduodenal boluses, and in intravenous infusion in three groups of rats with
      different total lipid (TL) content in the central lymph. The effect of a)
      different lipophilicity of DZ and DDZ, b) lymphatic TL content, and c) route of
      DZ administration on FL was determined. It was found that a) FL values of DZ
      exceeded the FL values of DDZ and b) FL values of DZ increased with increasing TL
      content in the lymph (an opposite relation was found in DDZ), and c) the highest
      FL value of DZ + DDZ sum after intravenous bolus administration was attained
      contrary to the lowest one after intraduodenal bolus administration.

PMID- 8884921
TI  - Elucidation of intestinal transport results as a function of age.
AB  - Duodenal, jejunal, ileal and caecal morphometrics were determined in chickens
      from hatching to the age of 15 weeks. The ratios of fresh weight/surface area and
      dry weight/surface area showed age-dependent changes in all the intestinal
      segments studied. The percentage of mucosa in each segment was also age-dependent
      in the first three weeks of life with a higher participation in the proximal
      intestine. Transport of 3-oxy-methyl-D-glucose was determined in the jejunum and
      ileum using a perfusion technique in vivo and expressed as a function of fresh
      weight, dry weight and surface area. The age-dependent differences observed in
      weight and mucosa composition of the intestine make it difficult to interpret the
      results of transport capacity during development. The optimum expression of
      results in the field of intestinal absorption may be the surface area, since it
      involves the smallest errors.

PMID- 8884922
TI  - Determination of coenzyme Q in human plasma.
AB  - Coenzyme Q10 (CoQ10) levels in human plasma were determined by high-performance
      liquid chromatography (HPLC) with UV detection. CoQ10 was dissociated from
      lipoproteins by methanol and subsequently cleaned-up on silica gel and octadecyl
      silica solid-phase extraction cartridges. HPLC separation was performed on a C18
      reversed-phase column. The methanol-hexane mobile phase provided a greater
      possibility of separation procedure adjustment allowing the shortest possible
      elution time without loss of resolution than a two-alcohol mobile phase.
      Quantitation was based on the peak heights using a standard addition method. The
      lower limit of detection was 8 ng on-column, corresponding to 90 micrograms
      ubiquinone per litre of plasma in an actual sample. Thirty-one randomly selected
      plasma samples from apparently healthy, 18 to 56-year-old individuals (males and
      females) were analyzed for total CoQ10. The average level in these subjects was
      0.47 +/- 0.18 mg/l with the range of 0.26-1.03 mg/l. The method was also applied
      to the determination of ubiquinone plasma level changes in one healthy volunteer
      over a period of one month and after oral intake of CoQ10.

PMID- 8884923
TI  - Liver, plasma and erythrocyte phospholipid content after chronic diazepam
      treatment in the rat.
AB  - Male Wistar rats were maintained on a nutritionally adequate diet and diazepam
      was administered in a dose of 10 mg/kg/day. Control animals were pair-fed an
      adequate diet. Feeding was continued for 180 days, and the effects on the liver,
      plasma and erythrocyte phospholipid content were studied. It was found that the
      contents of sphingophospholipids and phosphatidylinositol + phosphatidylserine
      were significantly reduced in the erythrocytes of diazepam-treated rats. There
      was a significantly increased content of phosphatidylcholine in the liver an
      erythrocytes after 180 days of diazepam treatment. Such treatment did not cause
      statistically significant changes in the plasma of diazepam-treated rats. These
      investigations are in agreement with the hypothesis that extended or chronic use
      of drugs such as diazepam may alter membrane-dependent processes.

PMID- 8884924
TI  - Endothelin-1 significantly increased number of specific high-affinity 1,4
      dihydropyridine (DHP) binding sites photolabelled on vascular smooth muscle cells
      with (-)-[3H]-azidopine.
AB  - The effects of endothelin-1 (ET-1) on surface membrane Ca2+ channels were studied
      on cultured human embryonal vascular smooth muscle cells (VSMC) and on isolated
      rat aorta using photoaffinity labelling with DHP Ca2+ channel antagonist (-)-[3H]
      azidopine (AZI). The AZI-labelled saturable population of sites on VSMC with Bmax
      = 1.59 +/- 0.10 pmol/mg of protein and KD = 5.40 +/- 1.70 nmol/l; and 1.32 +/-
      0.11 pmol/mg w.w. and KD = 1.09 +/- 0.20 nmol/l in isolated rings of the rat
      aorta. Preincubation with ET-1 (0.1, 1.0 and 10 nmol/l) increased (in a
      concentration-dependent manner) the total number of sites specifically
      photolabelled on VSMC. The number of sites labelled with AZI on ET-1 preincubated
      VSMC increased markedly when divalent cations (Ca2+ or Mg2+ in other experiments)
      were present in the incubation medium. Specific photolabelling also significantly
      increased in VSMC pretreated with intrinsically photoreactive nifedipine. A
      protein kinase C inhibitor staurosporine, added to the incubation medium,
      significantly reduced the enhanced specific photolabelling after ET-1. The
      increase in specific photolabelling after ET-1 preincubation (+197 +/- 46%; P <
      0.05) was also observed in rings of the rat aorta and it was significantly
      reduced after preincubation with S-(+)-niguldipine.

PMID- 8884925
TI  - Anticlastogenic effect of S-2-(3-aminopropylamino) ethylphosphorothioic acid
      against X-rays in mice.
AB  - The anticlastogenic effect of the aminothiol agent S-2-(3-aminopropylamino)
      ethylphosphorothioic acid (WR-2721) against X-rays was assessed by in vivo mouse
      micronucleus assay. The frequency of micronuclei in the bone marrow of adult male
      Swiss mice treated with WR-2721, at a radioprotective dose of 200 mg/kg or 400
      mg/kg body weight, 15 or 30 min before exposure to a sublethal dose of 6 Gy X
      rays, was determined 24 h after X-irradiation. The protective effect of WR-2721
      against X-ray-induced clastogenicity was shown in the erythropoietic system. WR
      2721 administration prior to X-ray exposure was found to decrease the number of
      micronucleated polychromatic erythrocytes elevated by X-irradiation. The
      protection against the clastogenic activity of X-rays by WR-2721 was least
      evident when the thiol had been administered in the lower dose of 200 mg/kg body
      weight, 15 min before X-irradiation, and was most effective when giving WR-2721
      in the higher dose, 400 mg/kg body weight, 30 min prior to exposure of mice to X
      rays. Thus, the radioprotective effect of S-2-(3-aminopropylamino)
      ethylphosphorothioic acid against genotoxicity by X-rays appeared to depend on
      the dose given and the time intervals between WR-2721 administration and X
      irradiation of mice. A novel clinical application of the drug could be in its use
      to protect against radiation-therapy-induced genotoxic damage to normal cells.

PMID- 8884926
TI  - Measurement of fractional esterification rate of cholesterol in plasma depleted
      of apoprotein B containing lipoprotein: methods and normal values.
AB  - The distribution of differently sized HDL particles in the plasma can be assessed
      by measurement of the fractional rate of cholesterol esterification (FERHDL). We
      have characterized the isotopic assay and compared it to the enzymatic
      measurement of the decrease in HDL free cholesterol (mass assay). The normal
      values of FERHDL were established in 116 apparently healthy individuals. The
      isotopic assay is particularly sensitive to changes in the incubation temperature
      above 37 degrees C. The reproducibility of the assay in aliquots of plasma stored
      at -20 degrees C and -70 degrees C for 3 months and even up to 2 years was high.
      Intraindividual variability of FERHDL is low. In the subjects in whom FERHDL was
      measured over a 3-month and 2-5 years' period, FERHDL showed a low variability
      (97.5 +/- 2.6% and 101 +/- 6.0% respectively in a paired t-test). Comparison of
      the isotopic assay and the mass assay revealed that the isotopic assay was much
      more reproducible. Normal values of FERHDL and the HDL subspecies distribution
      (using gradient gel electrophoresis) were established in 63 men and 56 women. The
      average values of FERHDL were significantly higher in men (16.8 +/- 4.5%/h) than
      in women (10.6 +/- 3.6%/h) and correlated well with the distribution of the HDL
      subspecies. FERHDL radioassay as a highly reproducible method for the assessment
      of HDL subspecies distribution which may be suitable for both retrospective and
      prospective studies of diseases of atherogenous origin.

PMID- 8884927
TI  - Mathematical modelling of the concentration of microorganisms in the urinary
      bladder under simple conditions.
AB  - Mathematical relationships for simple models of the filling and evacuation of the
      urinary bladder have been found and analyzed. These make the determination of the
      concentration of microbes in the urinary bladder at a given moment possible in
      relation to different parameters such as the rate of urine flow from the ureters,
      the microbe concentration in urine, the reproduction rate of microorganisms, the
      capacity of the urinary bladder and the size of the residue which remains in the
      bladder after miction.

PMID- 8884928
TI  - Phospholipid composition in the rat heart exposed to pressure overload from
      birth.
AB  - A pressure overload was induced in 2-day-old male rats by abdominal aortic
      constriction, and the phospholipid composition of the left ventricle (LV) and the
      right ventricle (RV) were determined. Sixty days after the surgery, body weights
      was lower and LV weight were higher in aorta-constricted (AC) rats in comparison
      with shamoperated animals. Increased ventricular/body weight ratios indicated a
      significant degree of hypertrophy of LV and smaller hypertrophy of RV. The
      concentrations of total phospholipids (PL), choline phosphoglycerides (PC),
      ethanolamine phosphoglycerides (PE), diphosphatidylglycerol (DPG) and
      phosphatidylinositol (PI) were decreased in both ventricles of AC rats. The
      concentrations of sphingomyelin (SM) and plasmalogen PE (PLPE) increased in LV
      only. The changes in phospholipid composition in the developing pressure
      overloaded myocardium may contribute to altered membrane functions connected with
      heart hypertrophy.

PMID- 8884929
TI  - Visual evoked potential evidence for magnocellular system deficit in dyslexia.
AB  - Some recent studies on dyslexia have suggested a selective abnormality in the
      magnocellular visual pathway. To verify this hypothesis, we investigated motion
      onset visual evoked potentials (VEPs) (predominantly testing the magnocellular
      system) as well as pattern-reversal VEPs (presumably testing the parvocellular
      system) in 20 dyslexics and 16 controls (both groups with a mean age of 10.0
      years). Although the latencies and amplitudes of the main positive peak of
      pattern-reversal VEPs did not differ between the dyslexic and control group, the
      motion specific negative peak of motion-onset VEPs was significantly delayed (p <
      0.001) in dyslexics. Our results confirm a selective magnocellular pathway
      disorder in dyslexics and indicate that the motion-onset VEPs might serve as an
      objective method for early diagnosis of dyslexia.

PMID- 8884930
TI  - A new method for aversive Pavlovian conditioning of heart rate in rhesus monkeys.
AB  - Aversive Pavlovian conditioning is an important tool used to investigate
      neurobiological mechanisms underlying the acquisition and expression of fear.
      Most studies have used nonprimate species employing electrical shock as the
      unconditioned stimulus (US). Although important advances have been made in
      understanding the neural substrates of conditioned fear, the extent to which
      these findings apply to primates is unclear. Research in primates has not
      progressed because of the lack of a conditioning paradigm that does not use
      shock. Therefore, we developed a method that uses a US consisting of a loud noise
      coupled with a stream of compressed air aimed at the face to aversively condition
      heart rate response in rhesus monkeys. With this US, rhesus monkeys rapidly
      acquire a conditioned bradycardia. The availability of an easy, reliable, and
      efficient method of aversive conditioning that does not require electrical shock,
      will facilitate studies investigating neurobiological mechanisms underlying the
      acquisition and expression of fear in primates.

PMID- 8884931
TI  - Adaptive metabolic responses in females of the fighting breed submitted to
      different sequences of stress stimuli.
AB  - The objectives of this study were to evaluate the stress reaction and the
      metabolic adaptive effort in females of the fighting breed when submitted to
      different manipulation sequences. Nine 4- to 8-year-old bovine fighting breed
      females slaughtered to establish the basal levels of different blood parameters.
      A study was, then, conducted to examine the metabolic response in 30 2-year-old
      females, divided into 3 groups of 10 animals and submitted to different
      manipulations in each group: restraint- "open-field" -restraint, "open-field" 
      restraint, and transportation-restraint- "open-field" -restraint. The basal
      levels of the different blood parameters found were, in general, similar to the
      levels for cattle given in the literature. All the manipulations resulted in
      increases that were statistically different (p < 0.001) from basal levels, in
      terms of both cortisol plasma levels and the Specie Specific Experimental
      Response to Stress index (SSERTS). The stress of restraint (and the prior
      manipulations) seemed to mask the stress associated with the open-field and
      transport situations. In general, animals responded to 13 of the 15 parameters
      examined in the various experimental manipulations.

PMID- 8884932
TI  - The effect of adrenocorticotrophic hormone on water intake in mice.
AB  - The systemic administration of adrenocorticotrophic hormone (ACTH) stimulates the
      intake of sodium chloride and water in many species. In mice the daily intake of
      water may reach half of the total body water content. To establish whether this
      very high water intake was primary or secondary to the sodium chloride intake,
      Synacthen was infused s.c. at 2.8 micrograms/day by Alzet miniosmotic pump to
      mice that did not have access to sodium chloride solution. On low-sodium food,
      the daily water intake increased from 2.99 +/- 0.08 ml (mean +/- SEM) to 9.85 +/-
      0.74 ml (p < 0.05, n = 6) by day 7 of infusion and remained significantly higher
      than the control value until the fourth postinfusion day. On high-sodium food,
      the daily water intake also increased 350% from a higher baseline, 4.55 +/- 0.14
      ml, and returned to the control value by the second postinfusion day. The same
      ACTH treatment for 4 days increased plasma [Na] and appeared to expand plasma
      volume. The results show that a high water intake caused by ACTH administration
      in mice is not secondary to a concurrent increase in sodium chloride intake. The
      water intake may be induced by stimulation of the secretion of adrenal steroid
      hormones which increase plasma [Na].

PMID- 8884933
TI  - The muscarinic acetylcholine antagonist scopolamine impairs short-distance homing
      pigeon navigation.
AB  - The present study employed intramuscular (i.m.) injections of the acetylcholine
      (ACh) receptor antagonist scopolamine hydrobromide (0.10 mg/kg) to investigate
      the possible involvement of ACh in naturally occurring spatial navigation in
      homing pigeons (Columba livia). Control pigeons receiving injections of saline or
      scopolamine methylbromide, an ACh antagonist that does not cross the blood-brain
      barrier, were oriented in a homeward direction when released from a location 8 km
      from home. In contrast, pigeons injected with scopolamine hydrobromide (0.10
      mg/kg, i.m.) were less well oriented and took more time to return home from the
      same location. These results suggest that homing pigeon navigation is regulated,
      in part, by central cholinergic mechanisms.

PMID- 8884934
TI  - Short-term effects of alcohol consumption on appetite and energy intake.
AB  - The relationship between alcohol intake and obesity remains uncertain. Evidence
      suggesting that alcohol-derived energy may be unregulated points to an inability
      to maintain appetite, energy balance and, hence, body weight when alcohol is
      introduced to the diet. This study investigated the short-term effects of alcohol
      on hunger and energy intake in 20 lean women. On 4 occasions, subjects were given
      a randomised preload drink ('alcohol', 'no alcohol', 'carbohydrate', 'water')
      followed by visual analogue scales (VAS) rating hunger and an ad lib test meal.
      There was no difference in hunger ratings (p > 0.05) nor in the amount of energy
      consumed during the test meal (F = 1.66, p > 0.05) following any of the 4
      preloads. Consumption of the 2 high energy preload drinks ('alcohol', 0.91 MJ;
      'CHO', 0.72 MJ) did not result in a compensatory decrease in the amount of energy
      subsequently eaten (ad lib intake: 'alcohol' = 2.62 MJ, 0.32 SEM; 'no alcohol' =
      2.98 MJ, 0.28 SEM; 'CHO' = 2.93 MJ, 0.21 SEM; 'water' = 2.82 MJ, 0.25 SEM),
      suggesting either no physiological recognition or no regulation of energy
      consumed within a drink in quantities of less than 1 MJ. The addition of either
      alcoholic or CHO-containing carbonated beverages into the diet will result, in
      the short-term, to an overall increase in energy intake.

PMID- 8884935
TI  - Effects of chronic episodic hypoxia on monoamine metabolism and motor activity.
AB  - Chronic episodic hypoxia produces a wide array of cardiovascular dysfunctions in
      rats, including increases in blood pressure, heart rate, and sympathetic nerve
      activity. The action of episodic hypoxia might be related to low oxygen itself
      (hypoxemia) and/or combined with low CO2 (hypocapnia) resulting from
      hyperventilation. It is unknown whether or not the cardiovascular abnormalities
      are related to alterations in the central nervous system (CNS) that may be
      manifested as neurotransmitter and/or behavioral changes. In this study, we
      investigated effects of episodic eucapnic and hypocapnic hypoxia on monoamine
      metabolism in both CNS and adrenal glands, and on motor behavioral activity.
      Thirty-five male rats were divided into 3 groups. Experimental rats were exposed
      8 h daily to varying fractional concentrations of inspired oxygen (FiO2) and
      carbon dioxide (FiCO2) for 35 days. These consisted of brief exposures (3-6s) of
      episodic (twice every min) eucapnic (3.5% FiO2 and 10% FiCO2, n = 6) or
      hypocapnic (3.5% FiO2 and 0% FiCO2, n = 14) hypoxia, or room air (21% FiO2 and
      0.03% FiCO2, n = 15). Norepinephrine, dopamine, serotonin, and their metabolites
      in the hypothalamus, hippocampus, and adrenal glands were measured by high
      performance liquid chromatography (HPLC). Spontaneous behavioral activity was
      assessed for 30 min by automated activity monitors. Episodic hypocapnic hypoxia
      produced a decrease in dopamine turnover and eucapnic hypoxia increased
      norepinephrine levels in the hypothalamus. Animals exposed to hypocapnic hypoxia
      also exhibited a consistent increase in horizontal (walking) and vertical
      (rearing) activity, as well as in total activity time. From these results, it is
      concluded that episodic eucapnic and hypocapnic hypoxia may affect metabolism of
      different neurotransmitters in the CNS.

PMID- 8884936
TI  - A direct measure of satiety disturbance in patients with bulimia nervosa.
AB  - To determine whether patients with bulimia nervosa (BN) experience the
      development of satiety during a meal differently than control subjects, a novel
      laboratory meal procedure was employed. Eleven women with BN and 11 women without
      eating disorders consumed a yogurt shake meal after being instructed to binge.
      After each 75-g increment consumed, the subjects were signaled by a tone to fill
      out a questionnaire on which they were asked to rate various sensations on visual
      analog scales. The sensations included "Fullness", "Hunger", "Desire" for a
      favorite food, "Pleasantness" of consuming the shake, "Sickness", and having
      "Enough" to consume. Although patients, before purging, consumed significantly
      more food than the controls, who did not purge (1597 +/- 626.5 g vs. 1004 +/-
      362.5 g, mean +/- SD), their final questionnaire ratings were not significantly
      different from the controls' ratings. Patients ate significantly more than the
      controls before reaching 50% of their range of "Hunger" rating and 75% of their
      "Full", "Desire", "Sick", and "Enough" rating ranges. The patients also ate
      significantly more than the controls between 75% and 100% of their "Hunger"
      rating range. These data suggest that one possible mechanism for overeating in
      patients with BN may be their failure to perceive or respond as normal subjects
      do to the range of sensations associated with satiety. Collecting ratings as a
      function of intake may provide a method for assessing and studying eating
      disturbances in clinical populations.

PMID- 8884937
TI  - Long-term patterns of change in ERPs across repeated measurements.
AB  - Ten subjects were tested for eight sessions using an auditory oddball paradigm at
      1-week and 1-month intervals to examine the stability of multiple event-related
      potential (ERP) components, in terms of trait (between session) and state (within
      session) reliability. The between session reliabilities presented as intraclass
      correlations (r') were 0.54 for the P300 amplitude and 0.47 for the P300 latency.
      Pearson correlation coefficients, representing within-session reliabilities,
      ranged from 0.54 to 0.68 for P300 amplitude and 0.12 to 0.46 for P300 latency.
      Statistical analysis of results from the eight sessions demonstrated that session
      dependent reduction and recovery of the P300 amplitude occurred during the
      testing sessions. Other ERPs measurements such as N100-P300, N200-P300, N100, and
      N200 amplitudes did not exhibit any significant changes. The between- and within
      session reliabilities of P300 components suggest that P300 may be a reproducible
      biological marker of state and trait even across repeated measurements. We
      speculate that the observed long-term patterns of change in P300 may have
      reflected habituation and dishabituation of certain processes in the human
      central nervous system.

PMID- 8884938
TI  - Behavioral interactions increase pregnancy blocking by unfamiliar male meadow
      voles.
AB  - Unfamiliar male meadow voles induce pregnancy disruptions when they are in
      physical contact with females, but the presence of the female's original mate
      partially protects her from the blocking effects of an unfamiliar male. This
      research examines how behavioral interactions affect pregnancy disruptions by
      testing two hypotheses: a) original males protect females by reducing the
      aggressive interactions between females and strange males; and b) administration
      of clonidine, an alpha 2-adrenergic receptor agonist that decreases activity,
      aggression, and sexual motivation, will decrease the pregnancy-blocking ability
      of strange males. Strange males were more aggressive when the original sire was
      absent, indicating that this change in behavior may be related to their greater
      success in disrupting pregnancy. When injected with clonidine, males were less
      likely to block pregnancy, and they showed less contact and mating behavior than
      when they received saline injections. These results indicate that behavioral
      interactions are important for male-induced pregnancy disruptions in meadow
      voles.

PMID- 8884939
TI  - Antagonism of the renin-angiotensin system and water deprivation-induced NaCl
      intake in rats.
AB  - Adult male rats (n = 5-7 per group) were water deprived for 24 h with only food
      available. Then they had access to water for 2 h. At the end of the 2 h, 1.5%
      NaCl was offered to the animals and the intake was measured for another 2 h. The
      rats drank an average of 9.8 +/- 3.0 ml/120 min of 1.5% NaCl; water intake during
      this time was negligible (not more than 1.0 ml/120 min). Captopril injected i.p.
      at the doses of 12 and 24 mg/ kg induced 60-90% inhibition of the intake.
      Losartan or PD123319 injected i.c.v. induced 50-80% inhibition of the intake.
      Losartan (80 nmol) inhibited the intake at a lower dose than PD123319 (160 nmol).
      Neither losartan nor PD123319 inhibited 10% sucrose intake. The inhibition of
      1.5% NaCl intake was not related to alterations in arterial pressure. The results
      show that the antagonism of the renin-angiotensin system inhibits the 1.5% NaCl
      intake induced by water deprivation. The inhibition induced by the angiotensin II
      antagonists suggest that this peptide is important for the control of salt intake
      induced by water deprivation.

PMID- 8884940
TI  - Seasonality in squirrel monkeys (Saimiri sciureus): social facilitation by
      females.
AB  - The extent to which social living arrangements influenced seasonal changes in
      physiology and behavior was examined in adult squirrel monkeys (Saimiri
      sciureus). Data were collected over 20 months (encompassing two breeding seasons)
      from animals that were housed in three mixed-sex social configurations that
      varied in the number of heterosexual and isosexual social partners. For both
      sexes, the presence of multiple females was found to facilitate reproduction.
      Females housed with other females were more likely to exhibit seasonal ovarian
      cyclicity and tended to have higher conception rates. Social facilitation of
      reproduction was particularly prominent for subordinate females. The presence of
      same-sex companions also resulted in reduced adrenocortical output in females
      during the first nonbreeding season. In males, the availability of multiple
      females increased plasma testosterone levels, except in the presence of more
      dominant males. Seasonal increases in male weight coincided with increased
      cortisol levels and were most prominent in social groups containing multiple
      females. The influence of multiple females on male seasonality occurred despite
      the finding that male-female interactions were infrequent and, in fact, occurred
      less frequently when isosexual partners were available. Unexpectedly, affiliative
      social interactions between same-sex and opposite-sex partners occurred less
      frequently during the breeding season. As expected, behaviors associated with sex
      tended to increase during the breeding season. Very little agonism was observed
      during the course of the study and there was no evidence of interanimal
      competition for mates.

PMID- 8884941
TI  - A study of sleep in the European blackbird.
AB  - Sleep states in the blackbird, Turdus merula, were determined by recording the
      electroencephalogram (EEG), electrooculogram (EOG), electromyogram (EMG), and
      heart rate (HR), and from behavioral observations and responses to auditory
      stimulation by natural calls. The presence of changes in slow wave activity was
      determined from the power spectra of the EEG. Spectral power density in the 0.5
      4.0 Hz band during slow wave sleep (SWS) attained highest values in the first
      part of the night, then declined. This trend in EEG spectra, which occurred
      across the night, probably reflects a homeostatic process strikingly similar to
      that observed in mammals. The reactivity to natural calls during SWS episodes
      also decreased across the night. Episodes of interhemispheric EEG asymmetry,
      which typically lasted from 2 to 4 s, occurred when birds displayed the front
      sleep posture and they constituted 140-200 s of each night. Unihemispheric sleep
      episodes probably result from unilateral activation of the visual system, and
      they could be considered as an evolutionary adaptation. HR was highest in
      wakefulness and lower in sleep but, due to large variability, reliable
      discrimination between sleep and wakefulness could not be made. Comparison of the
      blackbird's behavior during 4 different nights revealed a strong effect of the
      first night on sleeping behavior. A significant reduction in back sleep posture
      occurred during the baseline night, when lead wires were connected.

PMID- 8884942
TI  - Effects of beta-CCE on retention of aversively- and appetitively-motivated tasks
      in rats.
AB  - Beta-carboline-3-carboxylic acid ethyl ester (beta-CCE; 1.0 or 5.0 mg/kg, i.p.)
      or vehicle control was administered to male Sprague-Dawley rats immediately after
      training in an aversively- or appetitively-motivated task. Aversively-motivated
      training consisted of a one-trial step-though inhibitory (passive) avoidance task
      with a 0.6 mA, 1.0 s foot shock. Retention was tested 21 days after training. The
      5.0 mg/kg dose of beta-CCE significantly enhanced retention performance in the
      inhibitory avoidance task compared to the vehicle control. For appetitive
      training, the animals learned a T-maze for water reward. Retention was tested 48
      h later, and neither dose of beta-CCE was found to affect retention performance.
      These results suggest that beta-CCE, when administered immediately after
      training, may alter retention performance of an aversively-motivated task but not
      an appetitive task.

PMID- 8884943
TI  - An animal model for type 2 alcoholism? Alcohol consumption and aggressive
      behavior following lesions in the raphe nuclei, medial hypothalamus, or ventral
      striatum-septal area.
AB  - Given the conspicuous association between aggressive antisocial traits and
      alcoholism in men, we investigated whether or not a link between defensive
      aggressive behavior and homecage alcohol consumption could be demonstrated in the
      laboratory rat. This was accomplished by observing ethanol intake and
      hyperreactivity towards the experimenter in rats made hyperdefensive by brain
      lesions. Rats with medial hypothalamic electrocoagulations showed a remarkable
      degree of hyperdefensiveness, lasting throughout the entire 6-week postoperative
      period. Alcohol intake, on the other hand, was not different from sham-operated
      controls when the beverage was offered as a plain 6% solution or in a 0.2%
      saccharin vehicle. When subjected to the stress of food restriction, which
      enhances ethanol intake in normal rats, medial hypothalamic subjects actually
      decreased their alcohol consumption. Electrolytic lesions in the dorsal and
      median raphe brought about a transient increase in defensive aggression, but no
      alteration in ethanol drinking. Animals with ibotenic acid-induced extensive
      lesions to the ventral striatum and septal area were not only viciously
      aggressive, but also drank considerably more alcohol than controls. Ibotenic acid
      lesioned rats did not respond to the saccharin or food-restriction conditions by
      increasing their alcohol intake further, perhaps because they drank at a maximal
      rate already during the plain ethanol-phase of the experiment. These observations
      show that basal forebrain dysfunction in the rat can give rise to excessive
      alcohol intake and heightened aggression, a constellation of behavioral symptoms
      observed in male type 2 alcoholics.

PMID- 8884944
TI  - Food deprivation-induced increases in hoarding by Siberian hamsters are not
      photoperiod-dependent.
AB  - Siberian hamsters increase food hoarding in response to chronic food restriction
      and food deprivation, conditions that lead to a loss of body mass and fat.
      Therefore, the first purpose of the present experiments was to test further the
      effects of food deprivation on food hoarding by varying the length and order of
      repeated fasts to address the following questions: 1. Does the magnitude of the
      food-hoarding response increase as food deprivation length increases? 2, Is the
      effect of good deprivation on food hoarding experience-dependent? Second, we were
      interested in testing the effects of short winter-like days (SDs) on food
      hoarding. We tested this by measuring food hoarding in long days (LDs) and SDs
      during baseline conditions and after food deprivation to address the following
      question: Does SD exposure increase baseline and food deprivation-induced
      hoarding due to the naturally occurring SD-induced decreases in body fat? During
      each experiment, we were interested in determining how hamsters utilize their
      food hoard (i.e., add to it and eat from it). Our results extended those of our
      previous studies in showing that: 1. Food-deprivation length and the initial food
      hoard size were not related to one another; 2. The maintenance of food-hoard size
      was proportional to the length of the fast; 3. The effects of a bout of food
      deprivation on food hoarding were dependent upon the lengths of previous fasts;
      4. Baseline food hoarding was not different between LD- and SD-exposed hamsters;
      5. The maintenance of food-hoard size, but not the initial fast-induced increases
      in food-hoard size, were increased in SDs; 6. Hamsters ate approximately 25-33%
      of their daily food intake from the food hoard under all conditions, with the
      degree of food replacement increasing as fast length was increased; and 7. The
      typical SD-induced decrease in food intake was reflected in the food eaten from
      the food supply found outside the burrow, but food eaten from the hoard was
      increased. Collectively, the results of the present experiments suggest that the
      initiation of food hoarding may be associated with short-term fluctuations in
      energy metabolism associated with fasting, but that the more long-term decreases
      in body mass (fat) are involved in the maintenance of food-hoard size.

PMID- 8884945
TI  - Temperature-dependent effects of ephedrine in the cold.
AB  - This experiment examined the effects of intraperitoneal ephedrine (5-25 mg/kg) on
      operant thermoregulatory behavior of rats in the cold (-8 degrees C), and of 10
      mg/kg on metabolic rate at a thermoneutral (22 degrees C) ambient temperature
      (Ta) and in the cold (5 degrees C). Posttest colonic temperature (Tc) decreased
      dose-dependently in the behavioral tests, yet the demand for heat varied little
      with respect to saline except for a significant reduction at the lowest dose
      tested (i.e., there was no compensation for the reduced Tc induced by ephedrine).
      Ephedrine had a potent thermogenic effect at a Ta of 22 degrees C, increasing
      both metabolic rate and Tc. In the cold, ephedrine reduced Tc, but this effect
      could not be accounted for by a reduction in metabolism, which was not
      significantly different from saline.

PMID- 8884946
TI  - The composition of the maintenance diet alters flavor-preference conditioning by
      intragastric fat infusions in rats.
AB  - Prior studies indicate that intragastric (IG) fat infusions condition only weak
      flavor preferences in chow-fed rats using brief daily training sessions. The
      present study attempted to facilitate fat conditioning by feeding rats a high-fat
      maintenance diet or by adding an oily flavor to the conditioning stimuli. In
      Experiment 1, rats were fed restricted rations of either a chow-corn oil mixture
      (48% energy as fat, HF group) or regular chow (12% fat, LF group). During 1
      bottle training sessions, drinking a flavored (CS+, e.g., cherry) saccharin
      solution was paired with IG fat (7.1% corn oil emulsion). On other days, an
      alternate flavor (CS-, e.g., grape) was paired with IG water. In subsequent 2
      bottle tests between the CS+ and CS- flavors, the HF rats displayed a stronger
      CS+ preference than the LF rats (90% vs. 62%). Experiment 2 tested the effect of
      a semisynthetic HF maintenance diet (48% fat energy), using a conditioning
      procedure similar to that of Experiment 1. The rats displayed only a moderate
      (72%) CS+ preference. When switched to the chow-oil maintenance diet and
      retrained with new CS flavors, they developed a 90% CS+ preference. In Experiment
      3, chow-fed rats were trained and tested with oily CSs (i.e., 2% corn oil was
      added to flavored saccharin solutions). They failed to show a preference for the
      CS+ paired with IG oil. Thus, increasing the level of fat in the maintenance diet
      can greatly enhance preference conditioning with IG fat, but the amplitude of the
      effect is influenced by the composition of the high-fat food. In contrast, adding
      a fatty flavor to the conditioning stimuli did not improve fat conditioning.

PMID- 8884947
TI  - Characterization of sensorimotor performance, reproductive and aggressive
      behaviors in segmental trisomic 16 (Ts65Dn) mice.
AB  - In the present study, segmental trisomy 16 (Ts65Dn) mice, an animal model of Down
      Syndrome (DS), were examined for sensorimotor, reproductive, and aggression
      abnormalities associated with DS. The Ts65Dn mice exhibited no sensorimotor
      deficits in olfactory sensitivity, visual abilities, orientation reactions,
      forelimb strength, postural skills, balance/ coordination, climbing, or
      locomotion compared to genetically matched control B6EiC3HF1 mice. In mating
      tests, the percentage of Ts65Dn mice displaying intromissions when paired with
      estrous females was significantly less than that in controls. Although the
      percentage of Ts65Dn mice that mounted and ejaculated with an estrous female was
      marginally less than in controls, there were no significant differences on the
      other measures of reproductive behavioral performance. In aggression tests,
      Ts65Dn males showed increased offensive aggression in a neutral arena both when
      paired and among grouped males. Conversely, Ts65Dn mice exhibited less offensive
      aggression against an intruder in their home cage than control males. In sum,
      these mice possess some of the adaptive behavior abnormalities observed in DS
      patients; however, because the Ts65Dn mice do not have any observed sensorimotor
      deficits that could interfere with behavioral assessments, they may serve as a
      useful model for the study of behavioral impairments associated with DS.

PMID- 8884948
TI  - Generalized absence epilepsy and catalepsy in rats.
AB  - Adult WAG/Rij rats are considered adequate genetic models for human generalized
      absence epilepsy. Rats of this strain of 8, 12, and 18 weeks old and age-matched
      control Wistar rats were exposed to sound stimulation. After offset of
      stimulation, all WAG/Rij rats showed cataleptic or even cataplexic reactions,
      which could persist for up to 20 min. Age effects could be demonstrated. None of
      the Wistar rats showed cataleptic reactions. Electroencephalographic studies in
      WAG/Rij rats of 21 weeks showed that spike-wave discharges were abundantly
      present in the background electroencephalogram prior to sound stimulation. Age
      matched Wistar rats had almost no spike-wave discharges. Spike-wave discharges in
      WAG/Rij rats disappeared during sound stimulation and were then increased
      compared to the prestimulation and stimulation periods. The electroencephalogram
      during the cataleptic state was also characterized by the presence of large
      amplitude 2 Hz waves, interspersed with spike-wave discharges. The data suggest
      that the cataleptic state can be elicited in genetically epilepsy-prone rats. The
      youngest WAG/Rij rats showed no spike-wave discharges during the cataleptic
      state. In all, the data suggest that epilepsy-prone animals are sensitive for
      catalepsy at an age at which the EEG signs of generalized absence epilepsy are
      not yet manifest.

PMID- 8884949
TI  - A computer-aided procedure for measuring Hebb-Williams maze performance.
AB  - We describe a shortened procedure for testing mice over a 5-day interval on a
      swimming version of the Hebb-Williams maze. The mice are given 1 day of
      adaptation training, and are tested over the next 4 days on Hebb-Williams
      problems 1, 6, 12, and 5, in that order. As an animal swims through one of the
      maze problems, the computer screen shows the maze pattern, and an observer traces
      the path taken with a computer mouse. The computer program, Observe Software,
      stores the path sequence, determines the error score for that trial, and sends
      the information to a spreadsheet where it is available for statistical analyses.

PMID- 8884950
TI  - Blood pressure responses to acute exercise in type A and B females and males.
AB  - Cardiovascular responses to moderate steady-state exercise were studied in Type A
      and Type B males and females. Eighteen men and 17 women, ages 20 to 40 years,
      were chosen for Type A (males = 10, females = 10) and Type B (males = 8, females
      = 7) groups by means of the Jenkins Activity Survey (JAS). Subjects exercised on
      a electronic cycle ergometer at 60% O2peak for 20 min. Repeated measures analysis
      of variance (ANOVA) showed a significant Time (F(8,17) = 16.1, p < 0.001) and
      Group x Sex interaction (F(1,24) = 7.84, p < 0.01), with no differences evident
      between the male systolic blood pressures (SBPs), but an elevation in the SBP of
      the Type A female subject. SBP between all males and females were also
      significantly different (F(1,24) = 68.8, p < 0.0001). Males showed a greater SBP
      throughout the resting, exercise, and recovery time intervals when compared to
      females as a group, diastolic blood pressures (DBP) showed a significant Time
      effect (F(8,17) = 11.8, p < 0.0001) with a significant Time x Group x Sex
      interaction (F(8,17) = 3.1, p < 0.02). Significant Sex effects (F(1,24) = 12.4, p
      < 0.002) and a marginal Group x Sex interaction were also observed (F(1,24) =
      3.67, p < 0.067), with Type B females having the greatest reduction in DBP at 15
      min (59.0 +/- 5.6 vs. 71.7 +/- 3.2 mmHg) and 20 min (50.0 +/- 3.3 vs. 67.3 +/-
      3.9 mmHg) or exercise when compared to Type As. There were significant DBP
      differences between males and females throughout rest, at 5 and 20 min of
      exercise, and in both recovery time periods. The data only reveal significant
      differences in DBP between Type A and B males at 20 min of exercise [64.2 +/- 3.3
      (A) and 72.6 +/- 1.2 (B) mmHg]. No significant Group main effect was evident.
      These data suggest that hemodynamic and other physiological responses to exercise
      in females, particularly Type A, vary from males according to behavioral types
      associated with differing physiology.

PMID- 8884951
TI  - Effects of microinjections of the neuropeptide substance P in the dorsal
      periaqueductal gray on the behaviour of rats in the plus-maze test.
AB  - Currently, the participation of neuropeptides in the generation of aversive
      states in the dorsal periaqueductal gray matter (DPAG) is poorly understood. The
      elevated plus maze (EPM) is widely used for studying the neurobiological
      mechanisms of anxiety in the laboratory. One difficulty with this test has been
      to evaluate the involvement of GABA mechanisms in the DPAG substrates of
      aversion, because microinjections of GABA receptor blockers in this region cause
      an intense behavioral activation. In this study, we examined in the EPM the
      effects of semicarbazide, a drug that acts indirectly on GABA neurotransmission
      through inhibition of the glutamic acid decarboxylase, and substance P (SP)
      following microinjections into the dorsal periaqueductal gray. Semicarbazide
      caused a clear decrease in the number of entries and time spent in the open arms.
      These results confirm previous data showing that GABA has a modulatory role in
      the DPAG, probably through reduction of tonic inhibitory mechanisms on neural
      substrates of aversion. A similar pattern of behavioral responses was observed
      with SP. However, these effects were more pronounced with intermediate doses of
      SP (25 ng), confirming the characteristic bell-shaped dose-effect function of
      this neuropeptide. The proaversive effects observed with DPAG microinjections of
      SP in the present study gain further relevance when combined with previous
      reports that have shown unconditioned and conditioned aversive effects following
      DPAG microinjections of SP in other animal models of aversion.

PMID- 8884952
TI  - Agmatine enhances caloric intake and dietary carbohydrate preference in satiated
      rats.
AB  - Agmatine is a decarboxylated metabolite of arginine endogenous to the brain. In
      vitro, agmatine inhibits binding of clonidine to alpha 2-adrenergic and
      imidazoline receptors. We have shown that acute administration of agmatine
      increases caloric intake and dietary carbohydrate preference in satiated rats. In
      contrast, agmatine does not modulate caloric intake in hungry rats. Furthermore,
      repeated administration of high doses of agmatine does not decrease its ability
      to stimulate appetite.

PMID- 8884953
TI  - Food and nutrition policy in the Republic of Ireland: where to from here?

PMID- 8884954
TI  - Consumption implications of agri-food policies.

PMID- 8884955
TI  - Nutrition policy: priorities for new research.

PMID- 8884956
TI  - Different techniques of food preparation and cooking: implication for dietary
      surveys.

PMID- 8884957
TI  - Clinical assessment in primary care: professional cooperation.

PMID- 8884958
TI  - Nutrition surveillance of Ireland.
AB  - In summary then we can say that diet in Ireland is changing continuously, that
      the patterns as documented in diet are consistent with the epidemiological
      patterns of the major chronic diseases, although predictions for the future will
      be complex because of both positive and negative changes in diet behaviours. The
      major influences on diet relate to changes in the food chain, which have been
      enormous in 100 years; at consumer level, health concerns appear to be one of
      many considerations in food choices. We need a more consistent, comprehensive
      database in order to make meaningful inferences about diet and health.
      Furthermore, to be really useful such databases should include both quantitative
      and qualitative information.

PMID- 8884959
TI  - Integration of nutritional data based on household budget surveys in European
      countries. DAFNE I Group. Data Food Networking.

PMID- 8884960
TI  - Nutrition assessment and dietary guidelines: experience from the Dutch Nutrition
      Surveillance System.

PMID- 8884961
TI  - Workshop on 'Measurement of energy expenditure.' Report of Macronutrient
      Metabolism Group Workshop.

PMID- 8884962
TI  - Sir David Cuthbertson Medal Lecture. Immunomodulatory and anti-inflammatory
      effects of n-3 polyunsaturated fatty acids.

PMID- 8884963
TI  - Relationship between the in vitro radiosensitivity of skin fibroblasts and the
      expression of subcutaneous fibrosis, telangiectasia, and skin erythema after
      radiotherapy.
AB  - OBJECTIVE: To investigate if the occurrence of subcutaneous fibrosis after
      radiotherapy in an unselected group of breast cancer patients is related to
      cellular radiosensitivity of skin fibroblasts as measured in a clonogenic assay.
      MATERIALS AND METHODS: An in vitro colony-forming assay of normal fibroblast
      radiosensitivity was applied to primary skin biopsies from 31 breast cancer
      patients who received post-mastectomy radiotherapy with large doses per fraction
      (2.7-3.9 Gy) more than 10 years earlier. Three clinical normal-tissue endpoints
      were assessed. Two late endpoints, subcutaneous fibrosis and telangiectasia, were
      evaluated in three treatment fields by a single experienced clinician. In
      addition, skin erythema had been assessed at the end of treatment by members of
      the staff and junior staff. From previous analyses of normal tissue response,
      individual clinical radiosensitivity could be assessed as "excess risk' of each
      of the three reactions. This was defined as the difference between the actual
      observed response in the patient and the expected response estimated from
      individual treatment characteristics in a linear quadratic (LQ) mixture model
      and, for the two late endpoints, with correction for the follow-up time. This
      clinical radioresponsiveness was compared with the in vitro radiosensitivity of
      the skin fibroblasts. To this end, the fractions of colony-forming cells after
      graded single doses were fitted by an LQ survival curve using non-linear
      regression from which the surviving fraction at 3.5 Gy (SF3.5) was estimated.
      Assessment at 3.5 Gy was chosen to reflect the fraction size during clinical
      radiotherapy. RESULTS: A statistically significant variability of in vitro
      radiosensitivity between patients could be detected for both SF2 (P = 0.0095) and
      SF3.5 (P = 0.0008). A significant correlation was observed between SF3.5 and
      excess risk of fibrosis (rs = -0.46, P = 0.009) while no association was found
      between fibroblast radiosensitivity and either the occurrence of severe skin
      telangiectasia or the acute endpoint skin erythema. CONCLUSION: These results
      suggest that variability in the occurrence of subcutaneous fibrosis, but not
      telangiectasia or erythema, after radiotherapy is partly accounted for by
      differences in cellular radiosensitivity of normal skin fibroblasts.

PMID- 8884964
TI  - Further studies on the possible relationship between radiation-induced reciprocal
      translocations and intrinsic radiosensitivity of human tumor cells.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to estimate yields of
      radiation-induced translocations in surviving cells of several human tumor cell
      lines and in normal diploid human fibroblasts, and to compare these yields with
      corresponding intrinsic radiosensitivities determined by standard colony
      formation assay. MATERIAL AND METHODS: The yields of radiation-induced reciprocal
      translocations were investigated by fluorescence in situ hybridization.
      Chromosomes no. 1 and no. 4 were 'painted' with fluorescent hybridization probes
      for whole chromosomes. Translocation yields and cell survival were determined for
      different doses up to 6 Gy of 200 kV X-rays. RESULTS: We observed a higher
      frequency of reciprocal translocations in the radiosensitive cells MCF-7 and MDA
      MB-436 than in the radioresistant cells CaSki, WiDr, A549 and normal skin
      fibroblasts. For primary squamous cell carcinoma cells, ZMK-1, an intermediate
      radiosensitivity and an intermediate translocation yield were observed. The dose
      dependence of translocation yields involving chromosomes no. 1 or no. 4 varied in
      different cell lines: it was linear or linear with a plateau at higher doses.
      CONCLUSIONS: A comparison of the data obtained with chromosomes no. 1 and no. 4
      in the investigated cell types, indicates that intrinsic radiosensitivity of
      different tumor cells observed at the survival level, is correlated with
      different translocation yields, respectively. This correlation was observed for
      all cell types investigated, independent of the number of copies of the painted
      chromosome per cell or the radiation dose. However, for low doses (under 1 Gy),
      the yields of translocations determined for the individual chromosomes seem to be
      too low for a discrimination between radioresistant or radiosensitive cells.

PMID- 8884965
TI  - Cell density dependent plating efficiency affects outcome and interpretation of
      colony forming assays.
AB  - BACKGROUND AND PURPOSE: The usefulness of colony forming assays (CFA) has been
      established for almost 40 years (Puck and Marcus, J.Exp.Med. 103: 653-666, 1956).
      Although time-consuming and not successful for all cell lines, it is generally
      considered to be the gold standard of assays for testing the sensitivity of cell
      lines to ionizing radiation or other cytotoxic agents in vitro. We recently found
      for several cell lines that the plating efficiencies of both control and
      irradiated cells is dependent upon the density of cells seeded for colony
      formation; that is, increasing cell inoculum levels resulted in a non-linear
      relationship with colony formation, even at relatively low colony numbers.
      MATERIAL AND METHODS: All data from a human melanoma cell line, transfected with
      c-myc or N-ras, as well as from normal human diploid fibroblasts, were taken to
      see how this phenomenon influenced outcome and interpretation of clonogenic
      assays. Survival was recalculated using all data, or only data with a linear
      relationship between inoculum level and colony formation. RESULTS: It is found
      that when data with a non-linear relationship between inoculum level and colony
      formation are included, survival can be underestimated due to inhibition of
      colony formation in treated cultures. CONCLUSION: For validity, colony forming
      assays must be standardized to assure a constant relationship between the cell
      density and colony forming efficiency. This usually requires a much lower density
      of colonies than has been typically published for many cell survival studies.

PMID- 8884966
TI  - Adjuvant postoperative radiotherapy in rectal cancer: 148 cases treated at
      Florence University with 8 years median follow-up.
AB  - BACKGROUND AND PURPOSE: To analyse the outcome, the treatment related side
      effects, the prognostic significance of clinical parameters in a group of
      patients with rectal cancer receiving postoperative radiotherapy after radical
      resection. MATERIALS AND METHODS: From 1980 to 1990 148 consecutive patients with
      rectal carcinoma stage B2-B3 or C1-C2-C3 were treated with postoperative
      radiotherapy after radical surgery. All patients received 50 Gy in 25 sessions in
      5 weeks. In 42 a "flash' dose of 5 Gy was also given within 24 h before surgery.
      Median follow up was 8.1 years. RESULTS: At 5 years the overall survival was 54%,
      the determined (cancer specific) survival 61%, the local recurrence-free survival
      88%. The influence of stage, histotype, distance from anal margin, type of
      surgery, number of involved nodes and flash dose were analysed. Overall and
      determined survival and distant metastasis rate were significantly influenced (P
      < 0.005) by the pathological stage. Patients with more than 3 involved nodes
      presented a significantly lower determined survival (P < 0.001) and a higher
      distant relapse rate (P < 0.005) than those with 3 or less involved nodes. A
      higher determined survival (P < 0.01) was also found in patients receiving the
      preoperative "flash'; this group was however unbalanced in respect to the
      relative number of cases with 3 or less involved nodes. The incidence of major
      side effects requiring surgery or hospitalization for medical treatment was 35%
      before 1985 and 12% thereafter. The systematic use of small bowel visualization
      during simulation and the discontinuation of the flash dose were the main
      modifications introduced in the second period. As a consequence of the small
      bowel visualization the size of lateral fields was slightly reduced and some
      patients were excluded from the treatment. CONCLUSIONS: Value of postoperative
      radiotherapy to decrease the incidence of local recurrence was confirmed in this
      retrospective study; the incidence of side effects was however considerable and
      did not support the addition of chemotherapy as advised by the NIH consensus
      meeting. Our policy was therefore moved to preoperative irradiation whose
      combination with chemotherapy was recently reported to be better tolerated and
      highly effective.

PMID- 8884968
TI  - The time course of development of late side effects after irradiation of the
      prostate with multiple fractions per day.
AB  - BACKGROUND AND PURPOSE: A group of patients with prostate cancer was irradiated
      in the early 1980s with a TID schedule, resulting in a very high frequency of
      side effects. The time course of development of severe late complications was
      evaluated. MATERIALS AND METHODS: We retrospectively reviewed the records of 91
      patients with prostate cancer, irradiated on a linear accelerator or a cobalt
      unit between 1980 and 1983. They received a split-course irradiation with
      multiple fractions per day (MFD) up to a nominal dose of 60 Gy. The rate of
      development of severe late urological and gastrointestinal complications, grade 3
      or more according to the RTOG scoring system, was analysed. RESULTS: The 5-year
      actuarial incidence of urological complications was 51%. After a lag time of a
      few months, patients develop "first events' at a nearly constant rate of 10% for
      5 years after treatment. Subsequent events ("all events') seem to continue to
      appear even after 5 years. The actuarial incidence at 5 years of gastrointestinal
      complications was 14%, with no new events developing later than 3 years after
      treatment. CONCLUSIONS: The irradiation schedule used resulted in an unacceptable
      high incidence of late side effects, probably due to incomplete repair between
      fractions. MFD fractions to the pelvis should be avoided, unless sufficient time
      in between fractions can be allowed. Moreover, the fact that after this treatment
      schedule with very pronounced biological effects, new severe complications
      continued to develop up to 5 years after therapy, indicates that sufficiently
      long follow-up time has to be respected when investigating new radiation
      techniques for pelvic tumours.

PMID- 8884967
TI  - Randomized clinical trial on accelerated 7 days per week fractionation in
      radiotherapy for head and neck cancer. Preliminary report on acute toxicity.
AB  - PURPOSE: Toxicity of an accelerated 7 days per week fractionation schedule (arm
      A) was evaluated and compared with a conventional 5 days per week treatment (arm
      B) in a randomized trial. MATERIALS AND METHODS: Forty-four patients with
      squamous cell carcinoma of the head and neck in stage T2-4Nzero-1Mzero were
      included in the study. Total dose and dose per fraction of 2.0 Gy given once-a
      day at 24 h intervals were the same in both arms of the trial. The only
      difference was the overall treatment time being 5 weeks in arm A and 7 weeks in
      arm B. RESULTS: Analysis of severe mucosal reactions shows significant difference
      between arm A and B, with regard to both maximum score and duration of severe
      mucositis. Confluent mucositis (score > 15 according to the Dische system)
      lasting longer than 3 weeks developed in 48% of patients in arm A and only in 5%
      in arm B. In group A seven (30%) late effects (osteo- and soft tissue necrosis)
      occurred during 7-12 month follow-up with two reactions (10%) in group B being
      suspected as late effects. There was significant association between acute
      reactions and late effects in arm A, suggesting that the late effects are
      consequential. CONCLUSION: The high incidence of severe acute reactions and
      consequential late effects suggests that the accelerated treatment in arm A
      (using daily fractions of 2.0 Gy, 7 days per week) gives unacceptable toxicity.

PMID- 8884969
TI  - Late radiotherapeutic morbidity in patients with carcinoma of the uterine cervix:
      the application of the French-Italian glossary.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to perform a retrospective
      analysis of the complications observed and the importance of delayed symptoms for
      radiotherapeutic morbidity in patients treated by radiotherapy alone for cervical
      cancer. MATERIALS AND METHODS: From 1979 to 1991, 145 patients with primary
      uterine cervical cancer were treated with external radiotherapy and intracavitary
      applications. During the follow-up, all signs, symptoms and therapy of late
      treatment complications were recorded. Complications were graded according to the
      French-Italian glossary. This glossary is used for recording morbidity after
      treatment of gynaecological cancer. RESULTS: Overall, 119 late complications were
      recorded. They were most frequently located in the gastro-intestinal system (53%)
      with a median time to development of 9 months. Urinary complications were
      recorded in 20%. Very few complications were recorded in vagina/uterus (12%) and
      pelvic soft tissue (5%). The probability of surviving without tumour recurrence
      and/or late combined moderate to severe organ morbidity decreased with increasing
      FIGO stage. CONCLUSIONS: For reporting gynaecological morbidity, the French
      Italian glossary is useful. Treatment optimization must take into account
      actuarial estimates of survival and morbidity.

PMID- 8884970
TI  - Use of PSA nadir to predict subsequent biochemical outcome following external
      beam radiation therapy for T1-2 adenocarcinoma of the prostate.
AB  - PURPOSE: This study assessed the ability of nadir prostate-specific antigen (PSA)
      to act as an early surrogate for subsequent freedom from biochemical failure
      following radiation therapy for T1-2 prostatic adenocarcinoma. METHODS AND
      MATERIALS: A retrospective analysis was performed on the biochemical outcome of
      314 consecutive men with T1-2 disease treated by conventional external beam
      radiation at the Massachusetts General Hospital. Minimum follow up was 2 years,
      and failure was defined as three successive rises in serum PSA of greater than
      10%. Kaplan-Meier actuarial analysis of outcome was employed. RESULTS: The
      overall 5-year freedom from biochemical progression was 63%. For those who
      achieved a PSA nadir of < or = 0.5 ng/ml (n = 123) it was 90%, for 0.6-1.0 ng/ml
      (n = 103) it was 55%, and for > 1.0 ng/ml (n = 88) it was 34%. Multivariate
      analysis showed an undetectable PSA nadir to be independent of Gleason grade and
      initial PSA in predicting subsequent outcome (P < 0.05). The likelihood of
      achieving an undetectable PSA nadir correlated strongly with the pretreatment
      value: 74% if this was below 4 ng/ml; 42% for those between 4.1 and 10 ng/ml; and
      32% for those above 10 ng/ml. CONCLUSION: A PSA nadir of < or = 0.5 ng/ml
      represents an early endpoint strongly predictive of a favorable outcome following
      radiation therapy which may be used for the rapid assessment of new radiation
      strategies.

PMID- 8884971
TI  - Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian
      carcinoma.
AB  - BACKGROUND: Paclitaxel has been shown to radiosensitize tumor cells in culture by
      arresting them in the most radiosensitive G2 and M cell cycle phases. In vivo
      preclinical studies are now necessary to obtain full insight into the
      radiopotentiating potential of this drug and its ability to increase the
      therapeutic gain of radiotherapy. We tested its ability to enhance the tumor
      radioresponse of an ovarian carcinoma and to influence the normal tissue
      radioresponse of recipient mice. METHODS: Mice bearing 8-mm isotransplants of a
      syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40
      mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both;
      radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor
      growth delay, tumor cure rate (TCD50 assay), and delay in tumor recurrences were
      measured. Normal tissue radioresponse was determined using jejunal crypt cell
      survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body
      irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4
      96 h before irradiation. RESULTS: Paclitaxel alone was effective against OCA-I,
      but its combination with irradiation produced supra-additive tumor growth delay.
      It also reduced TCD50 values and delayed tumor recurrences. The enhancement of
      tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time
      between paclitaxel administration and tumor irradiation increased up to 48 h, but
      then decreased again at 96 h. In contrast, paclitaxel protected jejunum against
      radiation damage by factors of 1.03 to 1.07 when given 24-96 h before
      irradiation. It showed some potentiation of damage (by a factor of 1.07), but
      only when given 4 h before irradiation. CONCLUSIONS: Paclitaxel potentiated tumor
      radioresponse if given within 4 days before irradiation, whereas it caused
      radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel
      significantly increased therapeutic gain and so has potential for use in
      combination with radiotherapy for pelvic malignancies.

PMID- 8884972
TI  - Multicentre dosimetry study of mantle treatment in Australia and New Zealand.
AB  - PURPOSE: To determine the difference between expected and measured dose for
      patients prescribed a mantle treatment for Hodgkin's disease and estimate the
      range of dose at critical sites and between different treatment centres. METHODS
      AND MATERIALS: Twenty three radiotherapy centres were surveyed with regard to the
      accuracy of dose delivery to a custom-built upper-torso phantom.
      Thermoluminescent dosimeters were used to monitor the delivered dose at sites
      such as mid-plane, spinal cord, neck, axilla and lung. RESULTS: The intended dose
      to the phantom at each centre was 1 Gy to central axis mid-plane. Of the centres
      surveyed, the median measured dose to this region was 0.96 Gy with a minimum of
      0.92 and a maximum of 1.00 Gy. Median dose to the axilla region was low (0.90 Gy)
      whereas median dose to the blocked lung and neck region were higher than
      expected, 0.18 Gy and 1.25 Gy, respectively. The 95% confidence interval on the
      reported relative dose using the 4000 thermoluminescence dosimetry readings in
      this study was +/- 1.5% CONCLUSION: In this controlled experiment, using
      conventional methods to calculate dose, there was a surprising variability in the
      dose delivered at the central axis mid-plane position. This was traced to lack of
      uniformity in the use of equivalent squares to calculate the output factor. The
      measured doses to axilla and lung are explained by photon and electron scattering
      effects. Centres, where dose compensation was included, had a superior dose
      homogeneity in the neck. The off-axis dose calculations depend on computer
      planning software but the magnitude of these differences is secondary to that of
      central axis mid-point dose differences. Improved consistency of dose calculation
      techniques between centres would enable more reliable dose response evaluation
      from multicentre clinical studies of Hodgkin's disease.

PMID- 8884973
TI  - Increase of surface dose using wound dressings during percutaneous radiotherapy
      with photons and electrons.
AB  - Different wound dressings are used for the supportive treatment of patients with
      radiation-induced skin lesions. Depending on beam quality and energy, an increase
      of the dose administered to the skin and thus an aggravated skin reaction is to
      be expected during percutaneous irradiation. The increase of the skin dose during
      irradiation with photons (Co60, 6 MV, 42 MV) and electrons (7 MeV, 20 MeV, 42
      MeV) was determined using thermoluminescence dosimetry. The use of wound
      dressings during electron irradiation and during soft irradiation therapy does
      not significantly increase the dose administered to the skin and does not
      therefore cause any problems. During irradiation with high energy photons only
      extremely thin dressings should be used; if there is an aggravated skin reaction,
      the dressing should be taken off before irradiation commences.

PMID- 8884974
TI  - Physical vs. biological objectives for treatment plan optimization.

PMID- 8884975
TI  - Probable risk of tumor induction after retro-orbital irradiation for Graves'
      ophthalmopathy.

PMID- 8884976
TI  - Involvement of phospholipase A2 and arachidonic acid in cholecystokinin-8-induced
      insulin secretion in rat islets.
AB  - Cholecystokinin (CCK) has been shown to stimulate insulin secretion through an
      effect which involves mediation by phospholipase C (PLC) and protein kinase C
      (PKC). However, data exist suggesting involvement also of other transduction
      pathways. We investigated possible involvement of phospholipase A2 (PLA2) and
      arachidonic acid (AA) in mechanisms of insulin secretion, induced by the C
      terminal octapeptide of CCK (CCK-8) in isolated rat islets. At 5.6 mM glucose,
      the specific PLA2 inhibitor p-amylcinnamoylantranilic acid (ACA; 50 microM)
      diminished CCK-8 (100 nM)-stimulated insulin secretion (by 57 +/- 16%; P =
      0.001). Furthermore, at 5.6 mM glucose, CCK-8 significantly increased the efflux
      of [3H]arachidonic acid from prelabelled islets (by 130 +/- 25%; P < 0.001).
      These results imply that CCK-8 activates PLA2 to form AA in islets. To study
      whether the insulinotropic effect of CCK-8 is due to AA per se or to its
      metabolites, the oxidative pathways of the AA metabolism were inhibited. However,
      the cyclooxygenase inhibitors, indomethacin (30 microM) and salicylate (1.25 mM)
      as well as the lipoxygenase inhibitors baicalein (1-100 microM) and esculetin
      (0.5-50 microM), did not affect CCK-8-induced insulin secretion. We conclude that
      CCK-8-induced insulin secretion is partially mediated by a pathway involving
      PLA2, and that the formed AA, rather than its metabolites, is of importance.

PMID- 8884977
TI  - A synthetic peptide representing residues 7 to 21 of human luteinizing hormone
      beta-subunit binds calcium, facilitates calcium uptake by liposomes and possesses
      sequence similarity to calcium-binding domains of calmodulin.
AB  - We have previously demonstrated that a synthetic peptide corresponding to
      residues 1 to 15 of hFSH-beta-subunit (hFSH-beta-(1-15)) shares sequence homology
      with the calcium-binding domains of calmodulin (CaM), binds calcium with an
      affinity similar to that of CaM-binding loop III (CaM III) and facilitates uptake
      of external calcium by liposomes and cultured rat Sertoli cells. We noted a
      sequence homologous to hFSH-beta-(1-15) between residues 7 to 21 of the beta
      subunits of both hLH and hCG. A peptide amide representing this region of hLH
      beta (hLH-beta-(7-21)) and an N-terminal truncated analog (hLH-beta-(10-21)) that
      more closely resembles the calcium-binding loops of calmodulin were synthesized
      and tested for their ability to bind 45Ca2+, and facilitate uptake of 45Ca2+ by
      liposomes. hLH-beta-(7-21) and hLH-beta-(10-21) bound significant amounts of
      45Ca2+ with affinities of 1.2 +/- 0.4 and 0.7 +/- 0.3 mM, respectively, values
      virtually identical to that reported for a synthetic peptide corresponding to CaM
      III. The two peptides also facilitated specific, concentration-related and
      saturable uptake of 45Ca2+ by liposomes, which was sensitive to blockade by
      voltage-independent calcium-channel antagonists. Our data suggest that residues 7
      to 21 of the beta-subunit of hLH may be associated with the previously
      demonstrated calcium requirement for specific binding of LH to its receptor, and
      that the calcium-binding property of this region is related to its ability to
      facilitate uptake of calcium into liposomes via the formation of calcium
      conducting transmembrane channels.

PMID- 8884978
TI  - Relationship between circulating levels of calcitonin gene-related peptide,
      nitric oxide metabolites and hemodynamic changes in human septic shock.
AB  - This study is aimed to investigate the relationship between plasma concentrations
      of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the
      vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P
      (SP), endotoxemia and hemodynamic changes in human septic shock. Thirteen
      patients with septic shock were studied within 6 h after the development of
      hypotension. Hemodynamic measurements and blood samples were recorded
      simultaneously at 2-h intervals from study admission. Eighteen normotensive
      patients with sepsis were included as control group of patients. On study entry,
      circulating levels of endotoxin did not relate to either CGRP or nitrite and
      nitrate plasma values. Septic shock patients had significantly higher plasma
      CGRP, and nitrite and nitrate concentrations, at each of the four time points,
      than patients with sepsis, as well as both groups of patients compared to normal
      subjects. No differences were found in plasma SP levels between the two groups of
      patients. For pooled data from all septic shock patients and measurements (n =
      52), both plasma concentrations of CGRP and nitrite and nitrate were inversely
      correlated, independently from each other, to systemic vascular resistance. On
      study admission and at 2-h intervals, plasma CGRP concentrations correlated
      directly with nitrite and nitrate values. Our observations, thus, point to CGRP
      acting in concert with NO as important mediators responsible for hypotension in
      human septic shock.

PMID- 8884979
TI  - Metabolism of enkephalins in head membranes of the leech Theromyzon tessulatum by
      peptidases: isolation of an enkephalin-degrading aminopeptidase.
AB  - Metabolism of leucine and methionine enkephalins by enzyme preparations from head
      parts of the leech Theromyzon tessulatum was investigated. Leech homogenate
      degraded enkephalins by cleavage of the Tyr1-Gly2 and Gly3-Phe4 bonds. The Tyr1
      Gly2-Gly3 was detected as a major metabolite when amastatin (aminopeptidase
      inhibitor) was present to prevent Tyr1-Gly2 breakdown. Around 50% of enkephalin
      degrading activity was isolated in a 20000 x g membrane fraction and was shown to
      be almost entirely due to an aminopeptidase activity. This enzyme, a homodimer of
      approx. 70 kDa, has been purified to homogeneity by a combined approach including
      gel permeation and anion exchange chromatographies followed by reversed-phase
      HPLC. This enkephalin-degrading aminopeptidase is a typical integral membrane
      'zincin' metalloprotein with an apparent k(m) of 30 microM, a specific activity
      of 12 nmol GGFM min-1 mg protein-1 and a catalytic efficiency (kcat/k(m)) of 46 x
      10(6) mol-1 min-1. This enzyme is specifically inhibited by amastatin (IC50 = 0.5
      microM), but not by bestatin and actinonin. In leech membranes, the other
      degrading activities performed at the same time were due to a neuropeptide
      endopeptidase (NEP)-like enzyme attack, inhibited by phosphoramidon (IC50 = 0.1
      microM) and in the case of the Met-enkephalin by a combined action of an
      angiotensin-converting-like enzyme, inhibited by captopril (IC50 = 0.2 microM)
      and the NEP-like enzyme. These two enzymes were previously isolated from head
      membranes of T. tessulatum and possess towards Met-enkephalin a catalytic
      efficiency (kcat/k(m)) of, respectively, 12 x 10(6) mol-1 min-1 and 78 x 10(6)
      mol-1 min-1. These findings constitute the first report in leeches on the nature
      and the sites of attack of the membrane peptidases involved in the metabolism of
      enkephalins and also the first biochemical evidence for a novel member of the
      aminopeptidase family.

PMID- 8884980
TI  - Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of
      acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of
      isobutyl methylxanthin and alpha-fluoromethylhistidine.
AB  - The ECL cells in the rat stomach release pancreastatin and histamine in response
      to gastrin stimulation. The present study compares the release of pancreastatin
      and histamine from the ECL cells and the secretion of acid from the parietal
      cells in response to gastrin, and examines how a markedly reduced histamine
      content in the ECL cells will affect the gastrin-evoked release of pancreastatin
      and the secretion of gastrin acid. Totally isolated, vascularly perfused stomachs
      were prepared from fasted rats. Some of the rats had been pre-treated for 24 h
      with (alpha-fluoromethylhistidine (alpha-FMH), resulting in 80% depletion of
      oxyntic mucosal histamine (mainly ECL-cell histamine). The stomachs were perfused
      with rat gastrin-17, alpha-FMH, isobutyl methylxanthine (IBMX), or vehicle in
      various combinations for 8 h. The venous outflow was collected (30-min samples)
      for determination of histamine and pancreastatin-like immunoreactivity (LI) and
      the gastric luminal outflow was collected for determination of H+. Gastrin raised
      the outflow of pancreastatin-LI and histamine but did not raise the acid output
      unless IBMX was added. The outflow of pancreastatin-LI and histamine was greater
      after gastrin + IBMX (at least during the first 4-h period) than after gastrin
      alone. alpha-FMH reduced gastrin-evoked histamine outflow but did not affect
      gastrin-evoked pancreastatin-LI outflow. Also the acid output in response to
      gastrin + IBMX was much reduced by alpha-FMH. In conclusion, increased levels of
      intracellular cAMP enhanced the gastrin-evoked release of pancreastatin-LI and
      histamine from the ECL cells and made it possible for histamine, released from
      the ECL cells, to cause acid secretion from the parietal cells. ECL-cell
      histamine depletion reduced the gastrin-evoked acid secretion; it did not affect
      the gastrin-evoked release of pancreastatin-LI.

PMID- 8884981
TI  - Atrial natriuretic factor modifies the composition of induced-salivary secretion
      in the rat.
AB  - We have previously reported that although the atrial natriuretic factor (ANF) was
      not a sialogogic agonist, it enhanced cholinergic, alpha-adrenergic and
      peptidergic (substance P) stimulated salivation in the submaxillary and parotid
      gland of the rat. The purpose of the present work was to study whether ANF
      modified the composition of agonist-induced saliva in the rat. Results showed
      that in the submaxillary gland, ANF increased sodium and decreased potassium
      excretion when salivation was stimulated by methacholine (MC) or substance P
      (SP). However, when salivation was induced by methoxamine (MX), ANF only
      increased sodium excretion. On the other hand, in the parotid gland, ANF
      increased both sodium and potassium excretion when salivation was induced either
      by MC or SP but did not modify electrolyte output in MX induced salivary
      secretion. Protein output and amylase activity were not modified by the presence
      of ANF when the aforementioned sialogogic agonists were used to elicit salivation
      in either gland. Although ANF did not modify the volume of isoproterenol (IP)
      induced saliva, it increased protein output in both glands and it increased
      amylase activity in the parotid gland. The present results suggest that ANF may
      play a role in the modulation of salivary secretion in the parotid and
      submaxillary glands of the rat. ANF effect is likely to be mediated by
      modifications in the calcium level linked to phosphoinositide metabolism within
      the acinar and/or the ductal cells of the salivary glands.

PMID- 8884983
TI  - Vasoactive intestinal peptide stimulates prostate-specific antigen secretion by
      LNCaP prostate cancer cells.
AB  - The secretion of prostate-specific antigen (PSA) by prostate cancer provides an
      important tool in the diagnosis and management of this disorder. While androgens
      are required for PSA synthesis, the neuroendocrine regulation of PSA secretion is
      less understood. Human prostate is extensively innervated with vasoactive
      intestinal peptide (VIP)-containing neurons, while both normal and malignant
      prostate cells contain VIP receptors. Therefore, we investigated the effects of
      VIP on PSA secretion by LNCaP prostate cancer cells. We found that 1-4-h VIP
      treatment produces 60-100% increases in PSA secretion by LNCaP cells. Increases
      in PSA secretion were seen with as little as 10(-10) M VIP with maximum effects
      at 10(-7) M. The predominant acute effect of VIP was to increase the secretion of
      stored PSA without increasing PSA mRNA. VIP's effect on PSA secretion involved
      the production of intracellular cAMP since all doses of VIP which increased
      secretion were associated with increased cyclic AMP and since dibutyryl-cyclic
      AMP treatment increased secretion similarly to VIP. These results suggest that
      VIP regulates PSA secretion by prostate cancer cells and also suggest a role for
      VIP to regulate PSA secretion by normal prostate epithelial cells.

PMID- 8884982
TI  - Inhibitory effect of neuropeptide Y on growth hormone secretion in rats is
      mediated by both Y1- and Y2-receptor subtypes and abolished after anterolateral
      deafferentation of the medial basal hypothalamus.
AB  - Neuropeptide Y (NPY) may play a physiological role in the regulation of growth
      hormone (GH) secretion by acting via somatostatin (SS) in the periventricular
      nucleus (PeV), as well as via the GH-releasing factor in the arcuate nucleus
      (ARC) of the medial basal hypothalamus (MBH). The objectives of the present study
      were to determine the neuron structures and receptor subtypes necessary for
      mediating the inhibitory effect of NPY on GH secretion in unanesthetized male
      rats. To eliminate the influence of hypophyseotropic SS, anterolateral
      deafferentation (ALC) of the hypothalamus was performed. Intracerebroventricular
      (i.c.v.) administration of 1.17 nmol of NPY decreased the blood level of GH for 3
      4 h in sham-operated rats, while the procedure was without effect in ALC rats.
      The i.c.v. administration of 1.17 nmol of a Y1-receptor agonist ([Leu31, Pro34]
      NPY) or a Y2-receptor agonist (NPY 13-36 and NPY 3-36) similarly suppressed the
      blood GH level. The data support the hypothesis that neuron structures
      anterolateral to the MBH are required for NPY-induced inhibition of GH secretion
      that is mediated via Y1- and Y2-receptor subtypes. Combined with data of other
      investigators, SS is likely the neurohumoral mediator of the effect of NPY on GH
      secretion.

PMID- 8884984
TI  - Immunological analysis of angiotensin AT2 receptors in peripheral tissues of
      neonatal and adult rats.
AB  - The peptide hormone angiotensin II (Ang II) is an important regulator of
      cardiovascular and body fluid homeostasis. Circulating Ang II mediates its
      physiological actions by activating Ang II receptors in both the periphery and
      the brain. Previous studies have demonstrated that Ang II receptor expression is
      high in neonates and decreases to adult levels as the animal matures. A greater
      proportion of this decline is due to reduced expression of the Type 2 (AT2)
      receptor subtype. In order to further investigate the expression of this receptor
      subtype, AT2-directed antisera were utilized to determine the expression of AT2
      receptors in both neonatal and adult rat peripheral tissues by immunoblot
      analysis. The pattern of AT2 receptor immunoreactivity was largely consistent
      with previous studies employing autoradiographic and radioligand binding assays
      in peripheral tissues. However, AT2 receptor immunoreactivity was not seen in the
      adrenal, despite earlier reports of AT2 receptor expression in this peripheral
      tissue. These immunohistochemical studies also suggested that AT2 receptors
      undergo tissue-specific post-translational processing during development.
      Collectively, these results identify immunoreactive AT2 receptor populations in
      neonatal and adult rat peripheral tissues and further strengthen the hypothesis
      of AT2 receptor heterogeneity.

PMID- 8884985
TI  - Dermatotoxic chemical stimulate of c-jun and c-fos transcription and AP-1 DNA
      binding in human keratinocytes.
AB  - In many organ/tissues rapid and transient increases in early-immediate gene
      responses, such as those that encode for the AP-1 family of transcription
      factors, occur in response to exogenous stimuli. Activation of AP-1, in turn,
      helps regulate the expression of genes involved in cell growth, inflammatory
      responses, and repair processes. In the present studies, we demonstrate that
      increases in AP-1 DNA binding activity, as well as c-jun and c-fos mRNA levels,
      occur in human keratinocytes in response to diverse dermatotoxic chemicals,
      including phenol and arsenic as well as phorbol ester, the latter employed as a
      positive control. The AP-1 DNA binding complex has affinity for the consensus AP
      1 sequence but not the CRE2 binding sequence of the proenkephalin promoter or the
      NF kappa B consensus sequence indicating that the response is relatively
      specific. The binding complex is composed of Jun:Fos heterodimers, including Jun
      B and Jun D. Evidence is provided suggesting that AP-1 binding is associated with
      an increase in IL-1 alpha expression, an early mediator of toxic response in the
      skin.

PMID- 8884986
TI  - Leukemia inhibitory factor induces a hypertrophic response mediated by gp130 in
      murine cardiac myocytes.
AB  - We examined the effects of an interleukin-6 related cytokine, leukemia inhibitory
      factor (LIF), on myocardial cells using cultured murine cardiac myocytes. LIF
      stimulation (1 x 10(3) U/ml) for 36 h increased the cell size of neonatal cardiac
      myocytes and increased [3H] leucine incorporation in both fetal and neonatal
      cardiac myocytes; the increase was more significant in fetal myocytes. LIF
      stimulation also increased the expression of c-fos mRNA, one of the immediate
      early genes. In addition, the expression of prepro-atrial natriuretic factor
      mRNA, one of the genes expressed in fetal myocardium and reactivated by
      hypertrophic stimulation, was increased after 48 h of incubation with LIF. LIF
      receptor mRNA was expressed in fetal, neonatal and adult murine hearts and
      cultured murine cardiac myocytes. LIF induced the tyrosine phosphorylation of
      gp130 within 15 min after it was added to cardiac myocytes. In addition, LIF mRNA
      was expressed in both cardiac myocytes and non-myocardial cells derived from
      hearts. These results suggest that LIF activates gp130 and induces myocardial
      hypertrophy by acting as an autocrine/paracrine factor in cardiac myocytes.

PMID- 8884987
TI  - Transgenic mice overexpressing metallothionein are not resistant to adriamycin
      cardiotoxicity.
AB  - Metallothionein (MT) induction, particularly by bismuth, is proposed to protect
      against toxic side effects of chemotherapy drugs such as adriamycin. In contrast,
      transgenic mice, which overexpressed cardiac MT, and also had moderately high
      heart glutathione concentrations, were not resistant to adriamycin-induced
      cardiotoxicity. Cardiotoxicity was assessed by survival, fluid accumulation and
      lipid peroxidation. Thus, higher than normal heart MT concentrations do not
      necessarily protect against adriamycin cardiotoxicity.

PMID- 8884988
TI  - The effect of gold on copper and zinc in kidney and in metallothionein.
AB  - The question as to the increase in copper and zinc contents in metallothionein in
      response to gold injection was examined. Each rat was injected intraperitoneally
      once with 0.9% NaCl or gold (5, 10 or 20 mg gold/kg b.w.). After gold injection,
      60.1-68.4% of the renal copper content was found in the cytosol. Although the
      copper contents in cytosol and kidneys of gold-injected rats were higher than
      those of control rats, they did not increase in response to gold injection.
      Approx. 61.7-68.5% of the zinc contents in kidneys were detected in cytosol. The
      distribution profiles of the renal cytosols of gold-injected rats on a Sephadex G
      75 column showed that the amount of the increased copper was attributable to the
      MT fraction. Although the copper content of MT of gold-injected rats were higher
      than those of control rats, they did not increase in response to gold injection.
      These results indicate that copper and zinc contents in metallothionein did not
      increase in response to gold injection.

PMID- 8884989
TI  - Mechanism of mobilization of cadmium by dithiocarbamates in rat primary
      hepatocyte cultures.
AB  - The mechanism of mobilization of cadmium (Cd) by N-benzyl-D-glucamine
      dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate
      (HBGD) in rat primary hepatocyte cultures was studied. Probenecid pretreatment
      increased Cd efflux from the hepatocytes by BGD, but did not affect Cd efflux by
      HBGD. p-Aminohippurate treatment had no effect on Cd efflux by the chelating
      agents. These results suggest that an enhancing effect of probenecid on the BGD
      induced Cd mobilization is due to its inhibitory effect on the glucuronidation of
      BGD and not its specific action on BGD transport. Verapamil and nicardipine had
      no effect on the chelating agent-induced Cd mobilization. Phlorizin did not
      affect Cd efflux by BGD or HBGD. Phloretin and cytochalasin B inhibited Cd efflux
      by the chelating agents. These results seem to be evidence that BGD and HBGD may
      be transported by a facilitated diffusion system in the hepatocytes.

PMID- 8884990
TI  - In vivo monitoring of .OH generation on jejunal ischemic injury by dialysis
      technique.
AB  - We applied an in vivo microdialysis technique to examine free radical generation
      following ischemic injury in the rat jejunum. For this purpose, we used a
      microdialysis probe holding system. The salicylate reacts with hydroxyl free
      radical (.OH) and generates 2,3-dihydroxybenzoic acid (DHBA), which can be
      measured electrochemically in picomole amounts by high-performance liquid
      chromatography (HPLC). Therefore, the former was used for trapping the .OH
      formation. Reperfusion of the jejunum produced progressive elevations in the
      levels of 2,3-DHBA achieving the maximums at 20 min, after which they decreased
      progressively to the baseline. These elevations were significant only after 10
      min- and 20 min-ischemia. However, this change was not significant in the case of
      30 min-ischemia. Ischemia-reperfusion of rat intestine caused morphological
      changes. These results suggest that .OH production is significantly reduced after
      30 min-ischemia providing thus the possibility for more severe intestinal damage.
      In conclusion our dialysis probe can be useful for the measurement of .OH
      generation following ischemia-reperfusion injury.

PMID- 8884991
TI  - Response of endogenous reduced glutathione through hepatic glutathione redox
      cycle to enhancement of hepatic lipid peroxidation with the development of acute
      liver injury in mice intoxicated with carbon tetrachloride.
AB  - In the liver of male ddY mice intoxicated once with carbon tetrachloride (CCl4),
      the change in lipid peroxide (LPO) level with the development of damage over a 24
      hr period after i.p. treatment of the toxicant (1.0 mL/kg) was compared with the
      changes in reduced glutathione (GSH) and oxidized glutathione (GSSG) levels,
      GSSG/GSH ratio, and activities of the glutathione redox cycle-related enzymes
      such as Se-dependent glutathione peroxidase (Se-GSH-px), glutathione reductase
      (GSSG reductase), and glucose-6-phosphate dehydrogenase (G-6-PDH) and of Se
      independent glutathione peroxidase (non-Se-GSH-px) with the development of damage
      during the same period. An apparent liver injury was observed 0.5 hr after CCl4
      treatment and the injury progressed rapidly later than 8 hr, judging from the
      activities of serum transaminases, marker enzymes of liver cell damage. Hepatic
      LPO level slightly increased once during the first 4 hr after CCl4 treatment and
      a marked increase in the level occurred later than 12 h, while serum LPO level
      increased later than 12 h. Hepatic GSH level decreased rapidly during the first 4
      hr after CCl4 treatment and the decreased level recovered slowly thereafter,
      although the recovered level did not reach the control level. Hepatic GSSG level
      rapidly increased once during the first 1 hr after CCl4 treatment and an increase
      in the level occurred again later than 12 h. Hepatic GSSG/GSH increased during
      the first 1 hr and later than 8 hr after CCl4 treatment, although the ratio was
      maintained above the control level later than 0.5 h. Hepatic Se-GSH-px activity
      increased during the first 2 hr after CCl4 treatment and later than 8 h, while
      hepatic non-Se-GSH-px activity increased during the first 1 hr but decreased
      below the control level at 8 and 12 h. Hepatic GSSG reductase activity decreased
      during the first 2 hr after CCl4 treatment but the decrease activity returned up
      to the control level at 8 h. Hepatic G-6-PDH activity increased rapidly during
      the first 2 hr after CCl4 treatment and the increase proceeded slowly thereafter.
      These results indicate that although hepatic lipid peroxidation is enhanced at
      early and progressed stages of liver injury in mice intoxicated once with CCl4,
      endogenous GSH through hepatic glutathione redox cycle can respond well to
      enhanced hepatic lipid peroxidation at an early stage of liver injury but not
      enough to enhanced hepatic lipid peroxidation at a progressed stage of liver
      injury.

PMID- 8884992
TI  - Suppression of enterotoxin-induced intestinal fluid secretion by wood creosote.
AB  - Wood creosote suppresses intestinal fluid secretion induced by heat-labile
      enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC). When rabbit jejunum
      is ligated into a 5-cm segment and LT is administered locally, it actively
      induces intestinal fluid secretion in a dose-dependent manner. Local
      administration of wood creosote together with a fixed dose of LT suppressed the
      LT-induced fluid secretion in a dose-dependent manner. At a 50-ng/segment dose of
      LT, 7.4 +/- 1.1 ml (n = 5) of fluid is secreted into an intestinal segment;
      coadministration of wood creosote (150 micrograms/segment) significantly (p <
      0.01) suppressed the fluid secretion to 2.4 +/- 2.3 ml. Based on these results,
      we conclude that the antidiarrheal activity of wood creosote is attributable to
      its antisecretory or proabsorptive effect (or both) on the intestine.

PMID- 8884993
TI  - Adrenoceptor mechanism involved in thiopental-induced potentiation of halothane
      epinephrine arrhythmias in dogs.
AB  - Although thiopental is known to potentiate halothane-epinephrine arrhythmias, the
      precise mechanism of this potentiation is obscure. The authors investigated the
      comparative role of alpha 1 and beta adrenergic actions in the thiopental-induced
      potentiation of halothane-epinephrine arrhythmias in dogs. Adult mongrel dogs
      were anesthetized with halothane alone (1.3%) or thiopental (20 mg kg-1) plus
      halothane and monitored continuously for systemic arterial pressures and for
      premature ventricular contractions. The arrhythmogenic doses of phenylephrine and
      isoproterenol were determined during the two anesthetic methods and the effect of
      thiopental on the arrhythmogenic action of alpha 1 and beta agonists was
      examined. Thiopental failed to exert a significant potentiation of arrhythmogenic
      effect of phenylephrine or isoproterenol, when these agents were administered
      separately. On the other hand, the potentiation of arrhythmogenicity by
      thiopental was remarkable in the case of combined administration of both the
      agonists, that is, thiopental enhanced the synergistic interaction between
      phenylephrine and isoproterenol for inducing arrhythmias during halothane
      anesthesia. In addition, the potentiation was more prominent when a low dose of
      isoproterenol and a high dose of phenylephrine was combined than that when a high
      dose of isoproterenol and a low dose of phenylephrine was given in combination.
      The results indicate that thiopental significantly potentiates the arrhythmogenic
      interaction of alpha 1 and beta adrenergic agonists administered concurrently,
      although individual potentiation of these agonists is not significant.

PMID- 8884994
TI  - Antiarrhythmic effects of LR-A/113 a new calcium antagonistic drug.
AB  - LR-A/113 is a benzothiazepine drug similar to diltiazem with Ca(2+)-antagonist
      properties. Our previous studies showed that LR-A/113 determines anthypertensive
      effects comparable to diltiazem in normotensive and hypertensive rats. The aim of
      this study is to determine LR-A/113 effects respect to verapamil and diltiazem on
      CaCl2, aconitine and ouabain arrhythmias. Experiments were carried out on
      normotensive anesthetized rats and guinea pigs treated with CaCl2, aconitine and
      ouabaine and pretreated or not with verapamil, diltiazem or LR-A/113. Verapamil,
      diltiazem and LR-A/113, significantly delayed onset of arrhythmias and cardiac
      standstill induced by CaCl2 and aconitine. Moreover, pretreatments with
      verapamil, diltiazem or LR-A/113 reduced occurrence of arrhythmias in animals. In
      our models of arrhythmias LR-A/113 showed a significant antiarrhythmic effect of
      a magnitude almost similar to diltiazem but lower than for verapamil.

PMID- 8884995
TI  - Lack of voltage-operated calcium channel in rat glioma C6 cells.
AB  - We examined whether rat glioma C6 cells have voltage-operated Ca2+ channel (VOC)
      or not. The addition of high K+ did not affect the cytoplasmic Ca2+ concentration
      ([Ca2+]i). In addition, BAY K 8644, a VOC against, did not increase [Ca2+]i even
      in the presence of high K+. Bombesin (BBS), an inositol trisphosphate-generating
      drug, and thapsigargin (TG), a microsomal Ca(2+)-ATPase inhibitor, increased
      [Ca2+]i, after which it decreased to a sustained, and still higher than original
      level. The addition of verapamil, diltiazem and nimodipine did not affect an
      increase in [Ca2+]i induced by BBS and TG. The addition of SK&F 96365, a receptor
      operated Ca2+ channel (ROC) blocker, reduced the sustained increase in [Ca2+]i
      induced by BBS and TG. The present results suggest that VOC does not exist in rat
      glioma C6 cells and this cell line is a good model for investigating signal
      transduction via ROC as glial cells.

PMID- 8884996
TI  - Mycoplasma pneumoniae community-acquired pneumonia: a review of 101 hospitalized
      adult patients.
AB  - The features of community-acquired Mycoplasma pneumoniae pneumonia (MP-CAP) were
      assessed in a prospective study of 101 adults who were hospitalized over the
      course of 1 year, and were compared with 245 patients who were hospitalized
      during the same period of time with community-acquired pneumonia (CAP) not caused
      by M. pneumoniae (non-MP-CAP). MP was the second most common etiology (29.2%) in
      all CAP patients, and the most common etiological agent (43.2%) in the 17- to 44
      year age group. In 65 patients (64.3%) at least one other pathogen was identified
      for CAP in addition to MP. Although the disease was most prevalent among younger
      patients, it also involved older and even elderly patients. Compared to non-MP
      CAP patients, the severity of disease was significantly lower on average in the
      MP-CAP group and the length of hospitalization was significantly shorter.
      Radiologic findings were the same in the two groups. Twenty-two MP-CAP patients
      recovered without receiving the treatment which is recognized as effective in
      this disease. We concluded that (1) in most patients with MP-CAP a second CAP
      pathogen can be identified serologically, (2) MP-CAP cannot be differentiated
      from non-MP-CAP on the basis of clinical, radiologic, or routine laboratory
      tests, and (3) in some MP-CAP patients the disease is self-limited, and in these
      patients the usefulness of standard antibiotic therapy is doubtful.

PMID- 8884997
TI  - Influence of cardiopulmonary disease on resolution of pulmonary embolism. A
      mathematical model to predict remaining defects at six months.
AB  - Recovery of lung perfusion after pulmonary embolism (PE) is conditioned by
      several factors. The aim of this study was to analyze the differences of
      reperfusion after PE between patients with and without preexisting
      cardiopulmonary disease, and to develop a mathematical model to predict, at
      diagnosis, the size of defects in lung perfusion scan at 6 months after
      treatment. We included 83 patients with diagnosis of PE in a non-concurrent
      cohort study (cohort I: 26 with preexisting cardiopulmonary disease, and cohort
      II: 57 without previous cardiopulmonary disease). Lung perfusion scan was
      performed at diagnosis, 7-10 days after treatment and at 6 months. The defect
      size was quantified following a numerical score. The recovery of perfusion after
      7-10 days was 33% in cohort I and 45% in cohort II, and 50% and 72%,
      respectively, at the last control at 6 months. A multiple-regression analysis was
      performed using the final size of defects at 6 months (y) as the dependent
      variable, and the defect size at diagnosis (x) and the presence of preexisting
      cardiopulmonary disease (z) as independent variables. The regression equation was
      y = 1.29 + 0.15x + 2.98z. We conclude that: (1) in patients with cardiopulmonary
      diseases, the remaining defects at 6 months were larger; (2) at diagnosis, using
      a mathematical model, it is possible to predict the size of the defects in lung
      perfusion scan at 6 months in patients with or without previous cardiopulmonary
      disease.

PMID- 8884998
TI  - Pleural fluid beta-2-microglobulin and angiotensin-converting enzyme
      concentrations in rheumatoid arthritis and tuberculosis.
AB  - Concentrations of beta 2-microglobulin (B2M) and angiotensin-converting enzyme
      (ACE) were measured in pleural fluid (Pf) and serum (S) of 364 patients with
      pleural effusions. Eleven patients had rheumatoid arthritis (RA), 36 verified
      tuberculosis (TB), 15 suspected TB, 120 cancer, 21 empyema, 34 pneumonia, 33
      various defined diseases, 67 effusions of unknown aetiology and 27 congestive
      heart failure. The median concentrations of Pf-B2M and Pf-ACE were significantly
      higher in patients with RA than in patients with any other disease (p < 0.005).
      Tuberculous effusions contained higher Pf-ACE concentrations than any other type
      of non-rheumatoid effusion (p < 0.05). With sensitivities of 91%, the specificity
      of Pf-B2M and Pf-ACE for the diagnosis of RA was 86% and 55%, respectively. Local
      cellular immune events probably account for the abundance of B2M and ACE in
      rheumatoid and tuberculous pleural effusions. Pf-B2M and Pf-ACE determinations
      may aid in the differentiation of rheumatoid and tuberculous pleurisy from other
      types of pleural disease.

PMID- 8884999
TI  - Protection of rat lung from elastase-induced elastic fiber degradation in vitro
      and from emphysema in vivo by a trifluoroacetylpeptide anilide inhibitor.
AB  - Trifluoroacetylpeptide anilides are powerful reversible inhibitors of human
      neutrophil elastase (HNE), a serine protease implicated in the pathogenesis of
      pulmonary emphysema. The in vitro effectiveness of three inhibitors, CF3CO-Phe
      Ala-NH-p-C6H4-CF3 (1), CF3CO-Val-Ala-NH-p-C6H4-CF3 (2) and CF3CO-Lys-Ala-NH-p
      C6H4-CH(CH3)2 (3) was analyzed. The protection of lung tissue sections of rats
      from the degradation induced by HNE has been evaluated quantitatively by
      automated image analysis. Inhibitor 1 (22 microM), 2 (50 microM) or 3 (35 and 70
      microM) significantly reduced the HNE-induced degradation of the elastin network
      by 75, 42, 54 and 44%, respectively. Inhibitor 3 was tested intratracheally on an
      experimental model of pulmonary emphysema. Rats that received the elastase
      inhibitor 1 h before instillation of HNE were significantly protected by 40% from
      experimental emphysema. Reduced protections were observed with the treatment by
      the inhibitor 1 or 4 h after challenge with the enzyme.

PMID- 8885000
TI  - The effect of polysomnography on sleep position: possible implications on the
      diagnosis of positional obstructive sleep apnea.
AB  - This prospective study was designed to determine if physical constraint due to
      the polysomnography (PSG) apparatus affects PSG results by inducing subjects to
      sleep in the supine position. Twelve patients found to have positional
      obstructive sleep apnea (OSA) during standard PSG returned for two additional
      nights of study during which no PSG leads were attached. The time spent supine
      was 56% greater during the PSG night than the non-PSG nights, 195 +/- 88.6 min
      during the baseline PSG and 125 +/- 84.6 min during the non-PSG nights (p <
      0.05). Therefore, PSG may overestimate the severity of OSA in some patients with
      positional OSA.

PMID- 8885001
TI  - Bronchodilator response in pulmonary disease at two different states of
      respiratory mechanics.
AB  - It would be convenient to be able to measure airway responsiveness to
      bronchodilator drugs with a sequential use of oscilloresistometry and spirometry,
      which may allow the comparison of the response to bronchodilator at two different
      states of respiratory mechanics i.e., resting tidal breathing at functional
      residual capacity (FRC) versus forced expiratory manoeuvre from total lung
      capacity to residual volume. The evaluation of airway resistance and forced
      expiratory volume at 1 s (FEV1) may thus assist in the interpretation of
      bronchial responsiveness tests (BRT) to pick up responders among non-responders
      to administered bronchodilator. Such a concept was verified in 54 patients with
      respiratory disease before and 10 min after inhalation of 200 micrograms of
      salbutamol. Within 10 min following salbutamol challenge the increase for forced
      vital capacity (FVC), FEV1 and peak expiratory flow rate (PEFR) was 23, 27 and
      39% in 27 asthmatic patients of group A (p < 0.005). On the other hand, 27
      patients with chronic obstructive pulmonary disease in group B did not show any
      significant change in FEV1 and PEFR (p > 0.05). However, they showed a decrease
      in airway resistance of 30% (p < 0.005) during normal tidal breathing at FRC.
      Twenty-two normal controls in group C showed values of airway resistance and
      expiratory flow rates to be within the normal range and the response to
      administered salbutamol inhalation was not significant (p > 0.05). It may be
      concluded that the airway responsiveness to bronchodilators using only FEV1 as an
      index of BRT should be interpreted with caution in non-responders because they
      may not be able to tolerate the mechanical challenge in the form of an FCV
      manoeuvre but show a significant decrease in airway resistance during resting
      tidal breathing at FRC.

PMID- 8885002
TI  - IgA immune response against the mycobacterial antigen A60 in patients with active
      pulmonary tuberculosis.
AB  - Searching for IgG and IgM against the mycobacterial antigen A60 has been
      recognized as a potential diagnostic tool for pulmonary tuberculosis. The role of
      detection of anti-A60 IgA in improving diagnostic accuracy of serology is not
      well known. In this study we measured with ELISA serum levels of both anti-A60
      IgG and IgA in 216 subjects. 88 healthy volunteers (44 PPD- and 44 PPD+), 44
      patients suffering from nontuberculous lung disease and 15 subjects with healed
      pulmonary tuberculosis constituted the control population; 69 patients with
      active pulmonary tuberculosis (35 cavitary forms, 26 productive forms and 8
      miliary forms) were examined. The sensitivity of IgG test was 73.9% in pulmonary
      tuberculosis (77.1% in cavitary forms, 65.4% in productive forms, 87.5% in
      miliary forms); the specificity of the test was 95.9%. For the IgA test we
      observed a sensitivity of 72.5% (74.3 in cavitary forms, 69.2% in productive
      forms, 75.0 in miliary forms) and a specificity of 93.9%. Combination of the two
      tests increased the sensitivity to 84.0% (+10.1% compared to IgG test, +11.5%
      compared to IgA test); the specificity decreased to 92.5% (-3.4% vs. IgG test; 
      1.4 vs. IgA test). In conclusion, the combined use of evaluation of anti-A60 IgG
      and IgA increases the accuracy of serological diagnosis of pulmonary
      tuberculosis.

PMID- 8885003
TI  - Are the pulmonary function tests and the markers of activity helpful to establish
      the prognosis of sarcoidosis?
AB  - The prognosis of sarcoidosis is difficult to establish. It depends mainly on the
      persistence of activity over time and the degree of functional impairment of the
      involved organs. The aim of this study was to analyze whether the pulmonary
      function tests and the more commonly used markers of activity, such as serum
      angiotensin-converting enzyme (SACE) and gallium-67 scan, are helpful to evaluate
      the prognosis of sarcoidosis, besides the clinical data. Over a 14-year period
      (1974-1987), 209 patients were diagnosed as having sarcoidosis at the Bellvitge
      Hospital, a 1,000-bed teaching hospital in Barcelona, Spain. Clinical,
      radiological, pulmonary function tests, and activity markers (SACE and gallium-67
      scan) data at diagnosis were collected and classified as variables, and a
      definition of disease activity was established. One hundred sixteen patients were
      on follow-up, had all the variables available and were included in the
      statistical analysis. A Cox proportional-hazard regression model identified the
      following variables as independently influencing the persistence of activity over
      time: absence of erythema nodosum [risk ratio (RR) = 2.78; 95% confidence
      interval (CI): 1.48-5.18], age > or = 40 years (RR = 1.67; 95% CI: 1.008-1.04),
      SACE level > or = mean + 2 SD U/ml (RR = 1.45; CI: 0.99-1.07), hyperglobulinemia
      (RR = 2.47; CI: 0.98-6.24), forced vital capacity < 80% predicted (RR = 2.17; CI:
      0.97-4.85), and male sex (RR = 1.8; CI: 0.95-3.45). We conclude that the
      pulmonary function tests and the SACE level but not the gallium scan are helpful
      to identify the factors predicting persistence of activity in sarcoidosis.
      Therefore, we recommend to add these tests to the initial clinical evaluation of
      patients with sarcoidosis in order to establish the prognosis and improve the
      therapeutic approach.

PMID- 8885004
TI  - Magnitude and determinants of short-term tachyphylaxis to methacholine in
      subjects with symptomatic or asymptomatic airway hyperresponsiveness and in
      normal controls.
AB  - Tachyphylaxis to methacholine has been reported in nonasthmatic subjects. In a
      recent study on the prevalence of airway hyperresponsiveness (AHR) and atopy, we
      performed duplicate methacholine inhalation tests at a 60-min interval, in
      subjects with symptomatic asthma (n = 33), asymptomatic AHR (AAHR) (n = 72) and
      in a group of normal subjects (n = 130); 135/235 subjects were atopic. All
      subjects had a respiratory questionnaire, allergy skin prick tests, blood
      eosinophil counts and determination of total serum IgE level. In asthmatic
      subjects, PC20 just failed to be significantly higher on a second methacholine
      challenge (p = 0.09); when they were stratified according to severity of AHR and
      use of inhaled corticosteroids, we observed a significant increase in PC20 on the
      second test in asthmatic subjects with mild AHR not using corticosteroids (p <
      0.01). In normal controls, PC20 methacholine was slightly increased on
      rechallenge (p < 0.01) as it was in those with AAHR (p < 0.01). There was no
      relationship between the magnitude of the change in PC20 and age, sex, baseline
      airway responsiveness, percent fall in FEV1 on the first challenge, atopic score,
      blood eosinophil counts and serum IgE levels. In conclusion, tachyphylaxis to
      methacholine is observed in normal or mild asthmatic subjects not using inhaled
      corticosteroids and in subjects with AAHR; however, in most subjects this change
      is of a small magnitude.

PMID- 8885005
TI  - Rhabdomyolysis following status asthmaticus.
AB  - A case of rhabdomyolysis following an asthmatic attack is reported. A 71-year-old
      man was admitted because of wheezing and hypoxemia. Brown urine was present on
      admission. Although these symptoms completely disappeared with the treatment with
      aminophylline, salbutamol and corticosteroid, transiently elevated serum creatine
      phosphokinase and myoglobinuria were present. Rhabdomyolysis has rarely been
      reported in cases of bronchial asthma. This case represents an extremely rare
      case of rhabdomyolysis following status asthmaticus.

PMID- 8885006
TI  - Idiopathic bilateral diaphragmatic paralysis: effectiveness of bilevel
      intermittent positive airway pressure.
AB  - A 49-year-old woman presented with idiopathic bilateral diaphragmatic paralysis.
      The patient benefited from bilevel intermittent positive airway pressure-type
      assisted ventilation with rapid, excellent and long-lasting results. This case
      emphasizes the need for correct diagnosis and therapeutic management,
      particularly with a bilevel intermittent positive airway pressure-type home
      ventilation technique, in idiopathic bilateral diaphragmatic paralysis.

PMID- 8885008
TI  - Pulmonary embolism presenting as acute abdominal pain.
AB  - Pulmonary embolism has protean manifestations. This report describes a 20-year
      old woman without risk factors with pulmonary embolism presenting as abdominal
      pain. Previous cases and potential etiologies of pain are reviewed.

PMID- 8885007
TI  - Combined resections of the diaphragm and the liver for a locally advanced non
      small-cell lung cancer.
AB  - A 73-year-old man was admitted to our hospital to undergo treatment for right
      lung cancer (large cell carcinoma) which had directly invaded the liver through
      the diaphragm, and presented with T3N0M0, stage IIIa disease. A right lower
      lobectomy was performed with lymph node dissection, combined with a partial
      resection of the diaphragm and the liver, as well as a reconstruction of the
      diaphragm using the latissimus dorsi muscle. The patient had an uneventful
      postoperative course and was free of disease 1 year later at the time when this
      paper was written.

PMID- 8885009
TI  - Healing of osseous submucous cleft palates with guided bone regeneration.
AB  - The aim of this study was to develop an experimental model in rats of an osseous
      submucous cleft palate and to examine if bone regeneration can be achieved in
      such defects by the placement of membranes according to the principle of guided
      tissue regeneration (GTR). An osseous submucous cleft palate defect (5 mm x 2 mm)
      was created surgically in Wistar rats. Membranes of expanded
      polytetrafluoroethylene were placed so that they covered both the nasal and the
      palatal aspect of the defect before the palatal mucoperiosteal flap was
      repositioned and sutured. Histological analysis after seven weeks of healing
      showed that significantly more test animals (5/9) healed with newly formed bone
      and a suture-like tissue in the middle of the defects than controls treated
      without membranes (0/17). In specimens evaluated macroscopically after 12 weeks,
      the corresponding rates for the test group were 12/12 compared with 0/13. These
      observations indicate that an experimental model of an osseous submucous cleft
      palate can be established in rats, and that complete osseous healing and creation
      of a midpalatal suture-like tissue in the bony defect is favoured by the
      placement of membranes according to the principle of GTR.

PMID- 8885010
TI  - Contact hypersensitivity is suppressed after sensitisation by
      dinitrofluorobenzene of early stage iso-skin grafts.
AB  - Isologous free skin grafts were applied to the backs of BALB/c mice and contact
      hypersensitivity studied by epicutaneous application of DNFB (2,4-dinitro-1
      fluorobenzene) to the grafted skin. In the first experiment, the grafted skin was
      sensitised and the elicitation reaction assessed by measuring the ear swelling
      after five days. Sensitisation was not successful until two weeks after grafting.
      In such non-responding animals, re-sensitisation with DNFB on the ungrafted skin
      area was also unsuccessful, indicating the establishment of immunological
      tolerance. This tolerance was considered antigen-specific, as re-sensitisation
      with oxazolone was successful. In the second experiment, spleen cell suspension,
      both untreated and treated in vitro with antiThy 1.2, antiLyt 1.2, and antiLyt
      2.2 antibody, from non-DNFB-responding mice was transferred into normal mice.
      Subsequently these mice were sensitised with DNFB. Sensitisation was not
      successful in the untreated group or in those treated with antiLyt 1.2 antibody.
      On the other hand, the groups treated with antiThy 1.2 and antiLyt 2.2 antibody
      did become sensitised. These results indicate that the unsuccessful delayed
      hypersensitivity of the grafted skin was caused by suppressor T cells. In
      addition, the density of epidermal Langerhans cells was reduced in the early
      stages of skin grafting and morphological abnormalities were present. From these
      results, we conclude that contact sensitisation during the early stage of
      grafting skin not only produces suppression of ear swelling but also induces
      antigen-specific tolerance. These results also suggest that the suppression
      depends on the antigen-specific suppressor cells and that acquirement of
      tolerance is associated with a reduction in the number of epidermal Langerhans
      cells in the grafted skin and abnormalities in their structure.

PMID- 8885011
TI  - Transdermal iontophoretic delivery of triamcinolone acetonide: a preliminary
      study in hairless rats.
AB  - Transdermal iontophoretic delivery of triamcinolone acetonide was examined using
      a commercially available iontophoretic system (Phoresor, Iomed) in hairless rats.
      A drug electrode containing triamcinolone acetonide 10 mg dissolved in 1 ml of
      N,N-dimethylacetamide and water (7/3 v/v) was connected to the positive pole of a
      Phoresor (set at 4 mA) and direct current was applied for 10, 30, or 90 minutes.
      The amount delivered to the skin tissues increased with time at a constant rate.
      Even after the drug electrode had been removed, triamcinolone acetonide was
      retained in the local skin tissues beneath where it had been for about 24 hours
      after 30 minutes iontophoresis. These results suggest that the iontophoresis with
      an organic solvent used as a drug vehicle is useful to increase transdermal
      absorption of compounds that do not dissolve completely in water.

PMID- 8885012
TI  - Microvascular free flaps in the treatment of defects of the lower legs.
AB  - Thirty-four microvascular free flaps were used to treat defects in the lower
      extremities after injuries. Twenty patients (74%) had severe open fractures
      (Gustilo type III B & C). Latissimus dorsi (n = 16) and iliac osteocutaneous (n =
      7) flaps were most commonly used for coverage, and the overall failure rate was
      9% (3/34). At follow up 29 of the patients (94%) had a reduced range of movement
      of the ankle, nine (29%) had some swelling and oedema, and 13 (42%) had
      occasional pain in the leg. Sixteen (52%) of the patients were limping, but 26
      (84%) could walk one kilometre or more with no problems. No legs were amputated.
      The unemployment rate increased from 1/34 (3%) to 6/31 (19%) at follow up. Twenty
      seven (87%) of our patients were satisfied with the results, despite the
      considerable and persistent limitation of function, and the increase in the
      unemployment rate.

PMID- 8885013
TI  - The bipedicled flap on the lower leg, a valuable old method? Its indications and
      limitations in 12 cases.
AB  - Covering defects of the lower leg is still an exceptional problem when tendons or
      bone are exposed within small defects, particularly in the malleolar region. We
      present 12 cases of successful wound closure on the lower leg with the versatile
      bipedicled flap. We had a low incidence of minor complications, whether it was
      used as a cutaneous, fasciocutaneous, or myo-fasciocutaneous flap, in some cases
      also based on underlying perforators to guarantee perfusion of the flap. If it is
      limited to selected indications and patients, the bipedicled flap may be a
      reliable alternative to other, more sophisticated methods of tissue transfer.

PMID- 8885014
TI  - Influence of the site of skin incision on the circulation in the nipple-areola
      complex after subcutaneous mastectomy in breast cancer.
AB  - Necrosis of the skin resulting from impaired perfusion is one possible
      complication of subcutaneous mastectomy. The aim of this study was to evaluate
      the influence of two differently sited skin incisions on the circulation in the
      nipple-areola complex and in the surrounding skin. Sixty-nine patients with
      invasive breast cancer underwent subcutaneous mastectomy and immediate
      reconstruction with a subcutaneously placed prosthesis. In 26 of them a "lazy-S"
      shaped horizontal lateral incision was made, and in 43 patients a transverse
      incision 1.5 cm above and parallel to the submammary fold. The skin circulation
      was measured by two methods, laser Doppler flowmetry (LDF) and fluorescein
      flowmetry, two or three days postoperatively. The skin circulation in the nipple
      areola complex and in the skin 2 cm above the complex was the same irrespective
      of which of the two incisions was used, both by LDF and fluorescein flowmetry,
      but 2 cm below the complex fluorescein flowmetry showed 36% lower circulation in
      the submammary incision group than in the group with a lazy-S incision (p <
      0.01), in contrast to LDF, which did not show any differences between the
      incisions. The circulation measured by LDF was higher in all three areas both
      with the lazy-S incision and with the submammary incision than in the opposite
      untreated breast. With fluorescein flowmetry there was a corresponding increase
      by 36% (p < 0.01) below the complex in the lazy-S incision group. There was no
      skin necrosis. In conclusion, the site of the skin incision used in this study
      did not influence the circulation in the nipple-areola complex or in the skin 2
      cm above the complex as measured by LDF and fluorescein flowmetry. However, there
      was a reduction of the superficial circulation as measured by fluorescein
      flowmetry 2 cm below the complex in the submammary incision group. The increased
      circulation in the breast operated on was probably the result of traumatic
      hyperaemia.

PMID- 8885015
TI  - Breast reconstruction and tissue expansion in irradiated versus not irradiated
      women after mastectomy.
AB  - Thirty-five women whose breast cancer had been treated by radiation and 111 in
      whom it had not underwent unilateral breast reconstruction with the tissue
      expansion technique after modified radical mastectomy. Their records were
      reviewed and in a questionnaire the patients reported their own opinion on the
      results. The two groups differed significantly, because those patients who had
      been irradiated had a more painful course of expansion and a less over-expansion.
      Their reconstructed breasts were harder, had more deformities, and they required
      significantly more capsulotomies. The irradiated group also reported less
      satisfaction with the cosmetic results and more unfulfilled expectations. Tissue
      expansion cannot therefore be recommended as a routine procedure for breast
      reconstruction in patients after irradiation. However, our results do not show
      whether other methods are better for these patients.

PMID- 8885016
TI  - Reduction mammaplasty: analysis of patients' weight, resection weights, and late
      complications.
AB  - The medical records of 291 patients who had undergone reduction mammaplasty were
      analysed. A total of 216 (74%) of the women were overweight and 67 (23%) to such
      a degree that according to our policy they should not have been candidates for
      operation. Most of the patients were young-199 (68%) were less than 40 years old
      and 110 (38%) were less than 25 years old. Total bilateral resection weights in
      many younger women were quite low. Of the 199 patients less than 40 years old 64
      (32%) had less than 500 g total bilateral resection weight whereas 85 (92%) of
      the women 40 years old or more had resections of more than 500 g. Late
      complications were few-the rate of infection was similar in all weight groups.
      Fat and nipple necrosis-although rare-were more likely to occur in the obese and
      in patients over 30 years old.

PMID- 8885017
TI  - Evaluation of a priority grouping system for patients undergoing reduction
      mammaplasty.
AB  - The consequences of an earlier published priority grouping system for reduction
      mammaplasty are described. The system is based on breast volume but gives
      priority to certain age groups (25 years or less and 60 years or more),
      asymmetry, and ptosis, whereas overweight is considered as a negative factor.
      Additional points are given for psychological or somatic symptoms, or both. A
      total of 210 patients, who had been operated on were evaluated, and based on
      their total priority score, patients were assigned to one of five priority
      groups. Only five of the patients operated on belonged to the two groups with the
      lowest priority which indicates that the grouping system is a useful tool for
      sorting waiting lists and making decisions about priorities. The impact of the
      age related score and the subjective extra score for somatic and psychological
      distress is, however, considerable and questionable. Most of the patients (57%)
      less than 21 years old were in the group with the highest priority. The mean time
      period between acceptance for operation and the actual operation is 14 months in
      this age and priority group, which is far less than any other group. We think
      that the main focus should be the actual size of the breast and we have therefore
      recently modified the grouping system and reduced the impact of age and variables
      based on subjective scoring.

PMID- 8885018
TI  - External device for tissue expansion: clinical evaluation of the skin extender.
AB  - Tissue expansion is a well known way of repairing soft tissue defects. However,
      traditional tissue expanders have certain disadvantages such as the need for
      repeated outpatient visits for the filling of the expander and a long period of
      time required before the final result is achieved. A series of other devices have
      recently been developed. We have evaluated one of these, a skin extender
      developed by Blomqvist and Steenfos, in 10 lesions of the extremities in nine
      adult patients. The defects ranged from 3.5-10 cm wide and the extenders were
      inserted under local anaesthesia. The patients were taught how to tighten the
      extenders themselves, so there was no need for repeated visits to the outpatient
      department. Nine of the 10 defects were excised within 14 days; the remaining one
      developed a wound infection. The results show that this skin extender is a
      simple, fast, and economical device for repairing soft tissue defects, and in
      certain cases it is more suitable than a traditional tissue expander. Its major
      drawback is unsightly scars in the normal skin beside the previous defect.

PMID- 8885019
TI  - Incidence and natural history of touch allodynia after open carpal tunnel
      release.
AB  - Open surgical decompression is believed to be a safe treatment with few
      complications. However, it was our subjective impression that its morbidity had
      been underestimated. Fifty one consecutive patients with carpal tunnel syndrome
      were evaluated prospectively for three years after operation. Twenty one patients
      (41%) experienced allodynia of the operated hand at one month after surgery, 13
      (25%) at three months, and three (6%) at 12 months. These were confirmed by
      significantly lowered pressure-pain thresholds over both the thenar and
      hypothenar eminences (p < 0.005). During the first month after operation all
      patients were relieved of nocturnal pain, and all clinical signs had disappeared
      at three months in all 51 patients. Our results confirm that open carpal tunnel
      decompression has a high success rate, but highlights a previously underestimated
      morbidity of postoperative allodynia.

PMID- 8885020
TI  - Ectrodactyly, ectodermal dysplasia, and cleft lip syndrome. Case report.
AB  - We describe five sporadic cases of the EEC syndrome (ectrodactyly, ectodermal
      dysplasia, and cleft lip). There are only a few reports of the syndrome being
      inherited in Japan. Two of the five patients had genitourinary anomalies and one
      mental retardation. Four of the five patients had clefts in the primary and
      secondary palate. All had deformities of the hands, polydactyly, syndactyly, and
      camptodactyly. Syndactyly could be a component of the syndrome.

PMID- 8885021
TI  - Entrapment of the metacarpophalangeal joint of the middle finger. Case report.
AB  - Locking of the second metacarpal joint is common, but locking of other metacarpal
      joints is unusual. We present a case, in which the joint of the third finger
      locked and the mechanism was an osteophyte catching of the ulnar accessory
      collateral ligament. In such a case, the joint should be explored through a
      palmar approach. Conservative treatment is not recommended.

PMID- 8885022
TI  - A flap to monitor a temporoparietal fascial flap. Case report.
AB  - The temporoparietal fascial flap is useful in reconstructions of the hands and
      feet as tendon gliding material, but it is difficult to monitor its viability
      postoperatively. We have monitored such flaps by attaching a small preauricular
      skin flap 2 x 1 cm in size to the vascular pedicle. This preauricular island flap
      can be used as a "monitoring" flap.

PMID- 8885023
TI  - Talking at work--professional advice-seeking at primary health care centres.
AB  - OBJECTIVES: To describe professional advice- and information-seeking at primary
      health care (PHC) centres. DESIGN: Prospective cross-sectional data collection
      using semi-structured interviews. Statistical analysis of association between
      team-based and centralized organization, profession and pattern of advice
      seeking. SETTING: 4 urban PHC centres in Ostergotland County, Sweden.
      PARTICIPANTS: 199 PHC centre staff members (25 doctors, 70 nurses, 49 nurses'
      aides, 12 medical laboratory technologists, 24 secretaries, 19 physiotherapists).
      Nine (4%) staff members did not participate in the study (4 doctors, 3 nurses, 1
      nurses' aide, and 1 secretary). MAIN OUTCOME MEASURES: Number of staff using an
      advice source. RESULTS: For organizational advice, PHC centre managers were
      consulted at the centrally organized PHC centres, while staff at centres using
      team organization more often consulted outside sources. Having no one to ask for
      advice on patient communication was more common in the centralized organization.
      Regarding medical advice, only nurses' aides differed by consulting their own
      profession rather than doctors. For patient communication problems, the
      professions shared an intra-professional advice pattern. CONCLUSIONS: The PHC
      centre staff maintain parallel overlapping networks of professional advice
      seeking. The observed networks can also be seen to answer simultaneous demands
      from patients, the local health care administration, social services and
      professional authorities. Straightforward ways to develop the professional
      communication at PHC centres would be to visualize these multiple dependencies
      and to support their optimal function in the organization.

PMID- 8885024
TI  - Auditing palliative care in one general practice over eight years.
AB  - OBJECTIVE: To document the delivery and outcome of palliative care in one
      practice. DESIGN: All appropriate deaths were documented over the period of the
      study. SETTING: One general practice of four doctors caring for 8000 patients in
      the North-West of England. SUBJECTS: All patients dying of malignant disease
      which had included a palliative phase of at least one week. MAIN OUTCOME
      MEASURES: Place of death; continuity of care; general practitioners' assessment
      of symptom relief; follow-up of bereaved relatives. RESULTS: 118 deaths from
      terminal malignant disease were recorded over eight years in my practice. 75%
      were being cared for by us (GPs) at the time of death. More detailed information
      was recorded on 64 of these patients showing generally "satisfactory" care.
      CONCLUSIONS: A simple audit can help maintain high standards of palliative care.
      General practitioners are encouraged to maintain registers of the care received
      by terminally-ill patients as an aid to quality assurance in this area.

PMID- 8885025
TI  - Prevalence of depression and clues to focus diagnosis. A study among Dutch
      general practice patients 65+ years of age.
AB  - AIMS: To assess the prevalence of depression in elderly patients presenting in
      general practice, and to assess which patient characteristics and presenting
      symptoms are useful clues for predicting depression. DESIGN: Cross-sectional
      survey based on data collected at the presenting consultation and at a subsequent
      domiciliary interview. SUBJECTS AND SETTING: 580 of 706 consecutive patients aged
      65+ years consulting 13 general practitioners in the Netherlands. METHOD: GPs
      entered data on presenting symptoms and their assessment of psychological state
      during the consultation. Formal psychiatric assessment was subsequently done at
      home using the Diagnostic Interview Schedule (plus additional questions to assess
      minor depression according to ICHPPC-2-Defined). Major depression and dysthymia
      were assessed with the Diagnostic Interview Schedule. RESULTS: The estimated
      prevalence of depression (both major and minor plus dysthymia) was 7.9%, and was
      very similar whether based on GP assessment or formal validated interview
      schedule, but the GPs did not identify the same patients as the formal
      psychiatric assessment. GPs identified only 26% (95% CI 4-71%) of patients with
      major depression. Clinical clues which could help the GP to suspect underlying
      depression were female gender, the presentation of vague symptoms, and
      gastrointestinal symptoms. CONCLUSIONS: Although presentation of symptoms does
      provide some clues about the likelihood of underlying depression, the sensitivity
      of GP diagnosis remains low and needs to be improved.

PMID- 8885026
TI  - A list system can help to reduce the proportion of out of hours referrals for
      male patients.
AB  - OBJECTIVE: To examine differences in referral patterns by general practitioners
      (GPs) with and GPs without a list of patients. DESIGN: Survey of all referrals
      from primary to secondary care during one week. SETTING: Central and northern
      Finland, in a region comprising 72% of the area of the country and one-third of
      the population. PARTICIPANTS: 851 GPs, of whom 199 (23%) had a list system.
      OUTCOME MEASURES: Referrals in terms of practice characteristics. RESULTS: There
      were 58760 consultations during the study period, and 2921 patients were referred
      to secondary care. GPs with a list referred 64% of all referred male patients and
      63% of all referred female patients during normal working hours. The
      corresponding referral figures for GPs without a list were 43% and 58%.
      CONCLUSION: GPs with a list of patients had a more appropriate distribution of
      referrals between normal and out of hours work than GPs without a list. Our
      results may help in developing solutions to problems of providing good primary
      health care.

PMID- 8885027
TI  - What attendance rate can be achieved for Pap smear screening? A case-control
      study of the characteristics of non-attenders and results of reminder efforts.
AB  - OBJECTIVE: To understand participation failures in a national Pap smear screening
      programme by studying characteristics of non-attenders and results of further
      reminder efforts. DESIGN: A case-control and an intervention study. SETTING: The
      community health centre in the town of Hafnarfjordur, Iceland. SUBJECTS: The
      target population comprised 2510 women aged 35-69, who were invited regularly
      every second year for cervical cancer screening. MAIN RESULTS: 2241 (89.3%) had
      attended screening during the preceding five years, 102 (4.1%) had never
      attended, and 167 (6.7%) had attended previously but not during the preceding
      five years. Women with a mental disorder and those who had never married were
      more likely not to attend. The most usual explanations given by non-attenders
      were that they did not like to participate, or they felt they did not need to,
      some of them because their uterus had been removed. Of the non-attenders 29
      (10.8%) came for a Pap smear after repeated reminding efforts. CONCLUSIONS: Total
      participation rate in cervical cancer screening programmes in Iceland is high.
      When efforts are taken to lower the non-attendance rate it has to be kept in mind
      that many women are unwilling or unable to participate in such preventive
      measures.

PMID- 8885028
TI  - Change in ranking order of prescribing patterns by age and sex standardization of
      the practice population--audit may be misleading.
AB  - OBJECTIVE: To demonstrate whether standardization of practice populations by age
      and sex changes the internal prescription ranking order of a group of practices.
      DESIGN: Data on the prescribing of cardiovascular drugs in a group of practices
      were obtained from a county-based database. Information on the age, sex, and
      numbers of patients per practice was also obtained. The direct standardization
      method was used to adjust practice populations for age and sex. SETTING: The town
      of Randers, Aarhus County, Denmark. SUBJECTS: 35 practices, 41 GPs. MAIN OUTCOME
      MEASURES: Ranking of the 35 practices with respect to number of prescribed daily
      doses of cardiovascular drugs in crude utilization index and standardized
      utilization index. The slope of the regression curve of variation between the
      practices. RESULTS: The change from crude to standardized utilization index gave
      an entirely new ranking order of the practices. Only four practices did not
      change ranking position, while four moved more than ten places. The slope between
      highest and lowest ranked practice did not diminish after standardization.
      CONCLUSION: Care should be taken when comparing peer prescribing patterns from
      crude utilization data, and we recommend prior age and sex standardization. Our
      results are of value in creating a more reliable basis for a debate on variation
      in prescribing patterns between peers.

PMID- 8885029
TI  - Anticoagulant treatment in primary health care in Finland.
AB  - OBJECTIVE: To establish the prevalence of anticoagulant (AC) treatment, the
      indications, and the quality of care in primary health care. DESIGN: A cross
      sectional study, in which patients on AC treatment were identified from
      laboratory records. The main and second indications for AC treatment and the last
      value of the AC-test were taken from medical records. SETTING: Eight Finnish
      health centres with a total population of 182091 inhabitants. RESULTS: A total of
      1255 patients on AC treatment were identified, 48% of them men. The mean age was
      68.9 years. The age-adjusted prevalence of AC treatment was 0.65%. The commonest
      main indication was atrial fibrillation (38%). It was the main or second
      indication in 591 patients (age-adjusted prevalence 0.30%). The next commonest
      main indication was deep vein thrombosis (15%), followed by pulmonary embolism
      (8%). A total of 274 (22%) patients were anticoagulated for cerebral circulatory
      disturbances. 86% of the latest prothrombin time values fell within recommended
      ranges. CONCLUSION: The prevalence of AC treatment in Finland seems to be high.
      The proportion of patients with atrial fibrillation is high, differing from the
      results in other countries. The monitoring of AC-treatment as the general
      practitioner's responsibility functions well. The quality of care is good, even
      in older age groups.

PMID- 8885030
TI  - What factors are of importance for infants' use of health and medical care during
      the first 18 months?
AB  - OBJECTIVE: To study factors of importance for infants' use of health and medical
      care. DESIGN: We studied the medical records of the mother during pregnancy (at
      the health centre, at the antenatal clinics, and at the department of obstetrics
      and gynaecology) and of her infant during the first 18 months of life (at the
      health centre, at the child health clinic, and at the departments of paediatrics
      and oto-rhino-laryngology). We also interviewed the mother when her infant was 18
      months old. SETTING: Teleborg health centre, Vaxjo, southern Sweden. SUBJECTS:
      206 infants and their mothers. MAIN OUTCOME MEASURES: Medical visits, to doctor
      or district nurse, during the infants' first 18 months of life, and factors of
      potential importance for those visits. RESULTS: A stepwise linear multiple
      regression analysis showed that the following factors were of importance for the
      infant's use of health and medical care: number of mother's visits to the health
      and medical services during pregnancy, mother being a primipara, and mother being
      a blue-collar worker. The model (12.98 + 0.52* (no. of mother's visits) + 2.19
      (if primipara) + 1.48 (if blue-collar worker)) was able to explain 8.6% of the
      number of infant's visits. CONCLUSION: The studied factors explained only a minor
      part of the infants' use of health and medical care.

PMID- 8885031
TI  - Sex differences in cardiovascular risk factors independent of abdominal fat
      distribution.
AB  - OBJECTIVE: To investigate sex differences in cardiovascular risk factors within a
      healthy middle-aged population. DESIGN: Cross-sectional, observational study.
      SETTING: Primary health care in Dalby, Sweden. PARTICIPANTS: 19 males and 19
      postmenopausal females, selected for normotension, and matched for age (58 years)
      and body mass index (26 kg/m2). MAIN OUTCOME MEASURES: At two visits, with a five
      year interval, subjects were investigated according to height, weight, and blood
      pressure (ambulant and in the doctor's surgery). The fat-free mass was calculated
      using the von Dobeln formula. Glucose metabolism was evaluated with an oral
      glucose tolerance test (glucose, insulin, C-peptide). Lipid levels, liver
      enzymes, and hormonal variables (cortisol, sex hormones) were also measured.
      RESULTS: Males showed higher levels than females of glucose, insulin,
      triglycerides, and liver enzymes at the first visit, even after elimination of
      the influence of differences in weight. At the follow-up visit, males also had a
      higher 24-hour diastolic blood pressure than females (79.4 vs. 71.8 mm Hg; p <
      0.01), as well as higher triglyceride levels (1.45 vs. 0.95 mmol/l; p < 0.05),
      even after elimination of the influence of abdominal fat distribution. No
      differences in smoking or daily intake of nutrients (per 1000 kcal) were seen,
      but alcohol intake differed in absolute terms (males 8.5 vs. females 2.3 g/d; p <
      0.05). CONCLUSION: Healthy middle-aged males differ in an unfavourable way from
      matched postmenopausal females in several cardiovascular risk factors. This is
      not fully explained by differences in abdominal fat distribution and sex hormone
      levels, nor by the influence of food intake and smoking habits.

PMID- 8885032
TI  - Results from an intervention programme dealing with cardiovascular risk factors.
      Experiences from a study of men aged 33-42 in Habo, Sweden.
AB  - OBJECTIVE: To evaluate the long-term effect of a health examination and
      intervention programme in a Swedish community. DESIGN: A health examination was
      carried out with the purpose of improving cardiovascular risk factors. A health
      profile was created as an educational tool, by means of which a nurse discussed
      the results of the health examination with the participants. Follow-up studies
      were carried out after 1 year and after 3-6 years. PARTICIPANTS: All men aged 33
      42 living in a Swedish community (Habo) were invited to the health examination.
      Altogether 652 participated, corresponding to a participation rate of 86.1%. MAIN
      RESULTS: In the 1-year follow-up study, improvement with respect to
      cardiovascular risk factors was seen in a high-risk group (n = 161) for systolic
      blood pressure and lifestyle factors such as alcohol consumption, smoking, mental
      stress, mental health, and for the sum of risk points according to the health
      profile. Corresponding improvement was not seen in other men of similar age in
      the same community who had not participated in the health survey. In the 3-6 year
      follow-up only minor improvements remained, mainly for blood pressure and sum of
      risk points. CONCLUSION: Even if the results are rather promising in the short
      run, it seems urgent to make the methods for improving cardiovascular risk
      factors better, especially with regard to long-term results.

PMID- 8885033
TI  - Magnetic resonance imaging of lower extremity muscles and isokinetic strength in
      foot dorsiflexors in patients with prior polio.
AB  - The thigh and lower leg of six patients with prior polio were examined using
      magnetic resonance imaging (MRI), and the strength of their weak foot
      dorsiflexors was measured isokinetically. Spinecho images of the lower
      extremities were visually evaluated on a semi-quantitative four-point scale, and
      T1 and T2 relaxation times of the lower leg anterior compartment were analysed.
      There were prominent MRI signs of randomly distributed muscle degeneration. The
      high signal intensity changes in the affected muscles on T1-weighted images and
      T1 and T2 values indicated replacement of muscle fibres with fat and the
      accumulation of tissue water, respectively. MRI findings were compared with
      isokinetic strength in foot dorsiflexor muscles. Foot dorsiflexor peak torque
      values at 30 deg/s ranged from 6 to 29 Nm. There was no significant correlation
      between MRI visual scoring, T1 and T2 relaxation times and peak torque values at
      30 deg/s. However, the most severe MRI changes with visual scoring and T2
      relaxation times were observed in the patients with the most pronounced muscle
      weakness.

PMID- 8885034
TI  - Recovery of finger sensibility and somatosensory evoked potentials following
      digit-to-digit replantation in man.
AB  - Recovery of finger sensation and digital nerve function following digit-to-digit
      replantation was studied in 14 patients by clinical sensory evaluation and
      somatosensory evoked potentials (SEP) to digital nerve stimulation. The mean
      interval between injury and surgery was 8 +/- 3h; that between surgery and study
      was 25 +/- 7 months. Sensory examination revealed a mild hypersensitivity to
      cold. Pinprick, touch and hot sensations had nearly complete recovery, while
      vibration and two-point discrimination were impaired. In digital SEPs from the
      replanted side, the N9 component was present and normal in 8 patients (57%),
      whereas the N13 and N20 components had prolonged latency with normal central
      conduction time. Absence of the N9 component appeared to correlate with a more
      proximal level of injury and poor surgical outcome. The present data indicate
      that sensory recovery of the replanted digits was in general satisfactory but
      incomplete, and that over half of the patients had normal digital nerve
      conduction.

PMID- 8885035
TI  - Cervicocephalic kinesthetic sensibility in patients with whiplash injury.
AB  - This study investigated cervicocephalic kinesthetic sensibility in patients with
      whiplash injury and the effects of a rehabilitation programme. Fourteen patients
      with a whiplash injury and 34 healthy subjects participated in this study. The
      ability to appreciate both movement and the position of the head with respect to
      the trunk was investigated. Active head repositioning was significantly less
      precise in the whiplash subjects compared to the control group. Repositioning was
      more precise in whiplash subjects after the 5-week rehabilitation programme.
      There was no correlation between error of repositioning in patients and pain
      intensity. It is probable that cervicocephalic kinesthesia is linked to sensory
      information from the extensive muscular and articular proprioceptive system. A
      flexion-extension injury to the neck may result in dysfunction of this system.

PMID- 8885036
TI  - Prolonged functional impairments after whiplash injury.
AB  - Thirty patients with whiplash injuries were examined 1 to 55 months after the
      accidents. Pain had appeared on the day of the accident in 24 (80%) of the
      patients and with different delays in the remainder. The mean pain intensity was
      43 mm (SD 26) on a visual analogue scale (VAS). All patients had pain in the
      neck, 17-33% had headache and 6-17% had pain in various regions of the arms.
      Thirteen patients (43%) suffered from constant pain, while 17 (57%) had pain-free
      periods. Muscle tenderness was higher at all tested sites compared with controls.
      The tolerance level to pressure pain in the index finger as well as grip strength
      and neck mobility was reduced compared with controls. The whiplash patients
      showed poorer mental well-being compared with a reference group representing the
      general population and compared with a group of tension-type headache patients.

PMID- 8885037
TI  - Disability and quality of life in individuals with muscular dystrophy.
AB  - In the county of Orebro, Sweden, 32 individuals with myotonic disorders and 25
      with other types of muscular dystrophy were examined. Disability was assessed
      with functional tests and standardized observations of muscle function (mainly
      based on those proposed by Dr. Brooke), a new self-administered questionnaire
      regarding the Activities of Daily Living (ADL) and the ADL staircase (based on
      Katz ADL index). The results of the different tests of disability were highly
      correlated. The Sickness Impact Profile and the Kaasa test were used for
      assessing the quality of life, and no significant differences were found between
      the groups of muscular dystrophy. In an explanatory factor analysis three main
      factors of disability were found. The factors "walk and move" and "finger
      function" were fair to good associated with the quality of life. This study
      offers an approach for research on the consequences of muscular dystrophy using
      established as well as new methods.

PMID- 8885038
TI  - The multi-dimensionality of the FIM motor items precludes an interval scaling
      using Rasch analysis.
AB  - Rasch analysis scaling is said to produce an interval scale of Functional
      Independence Measure (FIM) motor function items. Rasch analysis requires that the
      data to be analysed represent the influence of a single underlying unidimensional
      variable. A unidimensional interval scale of activities of daily living means
      that a person who can perform the most difficult item on a scale can also perform
      the easiest item. For a FIM motor function interval scale, the ability to climb
      stairs would imply necessarily and ability to eat normally. As this need not be
      the case, the FIM motor items do not constitute an adequate interval scale.
      Eating and walking are different activities, and a unidimensional construct
      linking them is unsatisfactory. A principal components analysis of the admission
      FIM motor function items of 515 consecutive patients admitted to an inpatient
      rehabilitation unit revealed that more than one significant factor was necessary
      to explain the variance in scores. The counter-factual and statistical evidence
      argues that a unidimensional construct does not underly the FIM motor function
      items, and the use of Rasch analysis will not lead to a description of interval
      properties of the FIM motor function items.

PMID- 8885039
TI  - A shoulder pain score: a comprehensive questionnaire for assessing pain in
      patients with shoulder complaints.
AB  - This study describes the validation and application of a comprehensive
      questionnaire (the shoulder pain score) in assessing pain experienced by patients
      with shoulder complaints. The shoulder pain score comprised six pain symptom
      questions selected from the literature, together with a 101-Numerical Rating
      Scale (NRS-101). The score was tested in a follow-up study of 101 patients with
      shoulder complaints. The coefficient for the internal consistency of the shoulder
      pain score was 0.82. A factor analysis disclosed two factors: one containing the
      NRS-101 with the "active" items of the shoulder pain score and another containing
      the "passive" items. The shoulder pain score gave a reliable impression of the
      pain experienced and proved to be a useful instrument for following the course of
      the disorder over time and giving an indication when a patient feels cured.

PMID- 8885040
TI  - Effects of transcutaneous electrical nerve stimulation on H-reflex and spinal
      spasticity.
AB  - The purpose of this study was to investigate the short-term effects of
      transcutaneous electrical nerve stimulation (TENS; 99 Hz; 250 ms pulses) on H
      reflex and spinal spasticity. Considering the reflex hyperexcitability commonly
      displayed in spinal cord-injured subjects, it was hypothesized that repetitive
      low threshold afferent stimulation would have an inhibitory effect on the triceps
      surae H-reflexes which could also be reflected by a decrease in plantarflexor
      spasticity. Clonus, Achilles tendon reflex and modified Ashworth evaluations were
      performed on 14 spinal cord-injured subjects prior to and after 30 minutes'
      application of TENS. Non-parametric statistical analyses (n = 14; alpha = 0.05)
      failed to reveal significant effects of TENS on H-reflex amplitude. However,
      there was a significant decrease in scores for the Achilles tendon reflex and the
      modified Ashworth test. The clonus score decreased in most subjects post-TENS,
      although not in a statistically significant manner. The present pilot results
      thus suggest that TENS appears to be effective in reducing spinal spasticity, as
      measured clinically.

PMID- 8885041
TI  - Decreased frontal cortical serotonin2A receptors in schizophrenia.
AB  - 5HT2A receptors were measured in the frontal cortex from schizophrenic and non
      schizophrenic subjects. There was a decrease in the density of 5HT2A receptors in
      Brodmann's areas 8, 9 and 10 from the schizophrenic subjects. In addition, there
      was an age-dependent decrease in the density of 5HT2A receptors in Brodmann's
      areas 9 from the non-schizophrenic subjects, which was absent in the
      schizophrenic subjects. Available evidence does not suggest that the change in
      5HT2A receptors in the schizophrenic subjects was a result of drug treatment
      before death. These data may indicate that decreased 5HT2A receptors in the
      frontal cortex are involved in the pathology of schizophrenia.

PMID- 8885042
TI  - Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder
      and stillbirths.
AB  - BACKGROUND: More than 40 studies have been done on seasonal birth patterns for
      schizophrenia, but only two small studies have been done for DSM-III-R bipolar
      disorder and none for schizoaffective disorder. Two studies have also reported a
      significant relationship between schizophrenia births and stillbirths. METHODS:
      In the largest study to date, birth data from four states was obtained on 126,987
      state psychiatric hospitals inpatients divided into 'process' schizophrenia
      (disorganized, catatonic, undifferentiated), paranoid schizophrenia,
      schizoaffective disorder, bipolar disorder and major depression. Time series
      analysis compared these births to all general births and to stillbirths. RESULTS:
      'Process' schizophrenia, paranoid schizophrenia, schizoaffective disorder and
      bipolar disorder all had statistically significant seasonal excess births from
      December through March (p = 0.0000). The largest excess was 5.8% for bipolar
      disorder. Major depression had significant excess births from March through May.
      Time series analysis showed statistically significant coherences between major
      depression and bipolar disorder (0.995) and between schizoaffective disorder and
      both 'process' schizophrenia (0.977) and bipolar disorder (0.977). Unexpectedly,
      a significant coherence was also found between paranoid schizophrenia and bipolar
      disorder (0.972). Excess stillbirths were found for each month from January
      through June and a significant coherence was found between stillbirths and
      paranoid schizophrenia (0.998). CONCLUSIONS: This study demonstrates that DSM-III
      R bipolar disorder and schizoaffective disorder both have an excess of winter
      births, similar to that found in schizophrenia. Time series analysis, however,
      suggests that the causes may not be identical. Major depression, by contrast, has
      an excess of spring births.

PMID- 8885044
TI  - Explaining sex differences in course and outcome in the functional psychoses.
AB  - We addressed the following three questions: (i) are there sex differences in
      outcome in the functional psychoses?, (ii) what is their effect size, and which
      variables mediate the effect of sex on outcome?, (iii) is the effect of sex
      diagnosis-specific? In a prospective study of 166 patients with recent onset
      psychosis, we established that 4-year outcome was more favourable for women.
      Female patients more often had a remitting illness course (OR = 3.0; 95% CI: 1.5
      5.9), were living independently 14% (4-24%) more of the time, had less evidence
      of negative symptoms over the follow-up period (OR = 0.3; 0.2-0.7) and were more
      likely to be employed at follow-up (3.6; 1.8-7.6). The findings did not appear
      diagnosis-specific, although the sample size was small to test for interaction
      with diagnostic category. Baseline occupational and social adjustment, clinical
      expression of illness and age and type of onset explained up to 60% of the sex
      effect. The processes underlying these factors mediate the effect of sex on
      outcome.

PMID- 8885043
TI  - Reproductive fitness in familial schizophrenia.
AB  - BACKGROUND: Reproductive fitness is an important factor in understanding
      inheritance in genetic disorders. The purpose of this study was to determine
      whether fitness is reduced in familial schizophrenia (FS) and if fitness in
      siblings differs from the norm. METHOD: The number of offspring in 36 subjects
      with RDC schizophrenia or schizoaffective disorder (SZ) and their 101 siblings
      from large FS families was compared with age-adjusted census figures. RESULTS:
      Fitness in the SZ group was significantly reduced: 23% of expected in males and
      51% of expected in females. Fitness of unaffected siblings was within census
      expectations. However, female siblings with schizophrenia spectrum features had
      increased fitness over census norms. Reduced fitness was correlated with low
      marital rates, poor functioning and positive symptoms. CONCLUSIONS: These results
      indicate that reduced fitness is an important genetic force in FS and is likely
      inherent to the illness. Sex differences are important and would need to be
      considered when examining maternal and paternal transmission of schizophrenia.
      The results support a proposed high mutation rate for schizophrenia, consistent
      with a dynamic mutation mechanism.

PMID- 8885045
TI  - Preattentive information processing as measured by backward masking and texton
      detection tasks in adolescents at high genetic risk for schizophrenia.
AB  - Schizophrenic patients have consistently been reported to show deficits in
      preattentive information processing as demonstrated by impairments in visual
      backward masking and texton detection tasks. Texton detection refers to Julesz's
      texton theory, which defines a certain limited number of texton elements (e.g.,
      one 'L' among many '+') that can be detected readily and simultaneously without
      attentional effort irrespective of the size of the rest of the visual field. The
      present study investigated whether deficits of preattentive information
      processing are more prevalent in a group of adolescents of high genetic risk for
      schizophrenia compared to matched control subjects. Although differences in the
      performance in visual backward masking tasks could not be detected with our
      experimental approach, preattentive texton detection was to a certain extent
      disturbed in subjects at risk. Moreover, subjects at risk did not show the
      advantage of the right hemisphere in processing texton elements which was found
      in the control group. This may point to a subtle dysfunction of the right
      hemisphere in the risk group. It is concluded from the present study that
      deficits in preattentive texton detection may represent an indicator for a
      schizophrenic disposition. However, further studies including other high risk
      groups, schizophrenics in remission and individuals with a schizotypal
      personality disorder are needed to confirm this hypothesis.

PMID- 8885046
TI  - Syndromes of schizotypy and timing of puberty.
AB  - Development regressive events such as pruning of synapses are implicated in
      schizophrenia with both over- and under-connectivity models proposed (Randall,
      Feinberg, Hoffman). Saugstad theorized that extremes of normal variation in age
      at puberty distinguish affective psychoses (early maturation) from schizophrenia
      (late maturation). In normal students we have found a three-factor structure of
      schizotypy traits (Active, Withdrawn and Unreality) which may parallel three
      syndrome models of schizophrenia. Here, in a sample of 161 students we examined
      relations between schizotypy and extremes in the timing of puberty. Relations
      were almost exclusively syndromal. Unreality was associated with both extremes
      when compared with a group of normal maturers. Comparing early with late
      maturers, early maturing females were found to be Withdrawn, with features of
      social withdrawal and anhedonia. In contrast, Withdrawn males were late maturers,
      with features of social withdrawal and social anxiety. In females it was the
      Active syndrome (odd speech, impulsivity and activity) that was associated with
      late maturation. The results have relevance for both neurophysiological and
      social theories of personality, sex differences and psychopathology.

PMID- 8885047
TI  - Cigarette use, drinking and voiding in schizophrenic patients with polydipsia and
      hyponatremia.
AB  - Pre-smoking versus post-smoking amounts of drinking and voiding were compared in
      ten state hospital patients with schizophrenia and polydipsia. Cigarette use was
      significantly correlated with total amount drunk but was not associated with
      increased drinking or decreased voiding immediately following smoking. These
      findings revealed no nicotine effects upon thirst drive or urinary output, but
      suggest that drinking and smoking represent associated repetitive behaviors.

PMID- 8885048
TI  - TAPS project 28: does reprovision benefit elderly long-stay mental patients?
AB  - A survey of all inpatients aged 70 years or more was conducted in one of London's
      mental hospitals in 1989. Baseline measures of cognitive and behavioural
      disabilities were established for each of the 130 functionally-ill long-stay
      patients. Three years later 71 patients were still alive, being equally
      distributed between hospital and community facilities. The study examines the
      outcomes of patients who had left hospital in comparison with a similar group who
      remained there. The results indicate that behaviour of patients who were settled
      in the community was stable and even improved slightly over time, as opposed to
      those who remained in hospital, who became more disturbed. Direct examinations
      demonstrate that while those who remained in hospital markedly deteriorated in
      their cognitive function, patients who left hospital had also declined, but to a
      much lesser extent. When considering the overall outcomes, we come to recognise
      the potential for stabilization and even improvement in the condition of ageing
      schizophrenics being moved from hospital to the community.

PMID- 8885049
TI  - Growth factors in normal ovarian follicle development.

PMID- 8885050
TI  - Growth factors in ovarian follicle atresia.

PMID- 8885051
TI  - Growth factors and polycystic ovarian syndrome.

PMID- 8885052
TI  - Growth factors and testicular function: relevance to disorders of spermatogenesis
      in humans.

PMID- 8885053
TI  - Oviductal-derived growth factors and cytokines: implication in preimplantation.

PMID- 8885054
TI  - Growth factors and cytokines in endometrium, embryonic development, and maternal:
      embryonic interactions.

PMID- 8885055
TI  - Steroid and growth factor regulation of matrix metalloproteinase expression and
      endometriosis.

PMID- 8885056
TI  - Peritoneal growth factors and endometriosis.

PMID- 8885057
TI  - Growth factors and cytokines in uterine leiomyomas.
AB  - Uterine leiomyomas, hard masses of smooth muscle-like tissue embedded in the
      myometrium, may be the most common tumors among humans. These tumors enlarge in
      as many as 30% of women over 30 years of age, cause significant morbidity, and
      are the most frequent indication for hysterectomy. Many researchers and
      clinicians have recently directed their attentions to understanding the etiology
      of these benign tumors, the conditions which cause their enlargement, and
      appropriate therapies which may be used as alternatives to hysterectomy. The
      ovarian steroid hormones estrogen and progesterone are known to play a central
      role in the pathology of leiomyomas. Both estrogen and progesterone contribute to
      the pathology of leiomyomas through gene regulation, but in opposing ways. During
      the follicular phase, estrogen maintains high expression of several genes which
      are normally expressed in the differentiated myometrium of pregnancy. During the
      luteal phase, progesterone can increase the mitotic activity of leiomyomas,
      particularly in younger women. Progesterone may act by inducing the production of
      growth factors and/or their respective receptors. This article surveys growth
      factors which may promote enlargement of susceptible leiomyomas. A potential role
      for cytokines in leiomyoma pathology is also discussed.

PMID- 8885058
TI  - Update '96 on pulmonary gas exchange pathophysiology in pneumonia.
AB  - The major determinant of abnormal pulmonary gas exchange in patients with
      pneumonia is characterized by marked increases in intrapulmonary shunt combined
      with mild to moderate ventilation-perfusion (VA/Q) inequalities. Other mechanisms
      influencing the levels of arterial hypoxemia, such as disequilibrium of alveolar
      to endcapillary oxygen diffusion or increased intrapulmonary parenchymal oxygen
      uptake, are trivial in the clinical arena. These pathophysiological findings
      mostly concur with the structural derangement of pneumonic areas. On breathing
      oxygen, the dispersion of pulmonary blood flow, an index sensitive to both normal
      and low VA/Q ratios, increases (worsens), suggesting that hypoxic pulmonary
      vasoconstriction is abolished, whereas intrapulmonary shunt remains unchanged.
      This response differs from that developed by patients with acute respiratory
      distress syndrome (ARDS) in whom shunt increases moderately, thereby suggesting
      the development of reabsorption atelectasis, but VA/Q abnormalities remain
      unaltered. The effects of different drugs aimed at blocking the cyclooxygenase
      pathway to potentially enhance the mitigated hypoxic pulmonary vasoconstriction
      in the consolidated lung regions have shown to be individually variable and, in
      general, minimally beneficial; in contrast, the recent introduction of
      aerosolized vasodilators may benefit patients.

PMID- 8885059
TI  - New etiopathogenic concepts of ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia develops as a consequence of impaired host
      defenses and exposure to large numbers of potential pathogens. Both of these
      processes interact and allow colonization of the airways with enteric gram
      negative bacteria to occur through the molecular mechanism of bacterial
      adherence. Bacterial adherence is a cell-cell interaction mediated by the
      following variables: (1) host receptors, (2) bacterial adhesins, and (3) the
      proper microenvironment on the respiratory mucosa. For gram-negative bacteria, an
      important adhesin may be the pili that project from the cell surface, and
      important epithelial receptors for adhesins may be glycoproteins contained in
      respiratory mucus. The proper microenvironment for adherence to take place is a
      mixture of exposed cell receptors, prolonged bacterial-epithelial cell contact,
      impaired airway defenses, presence of proteases, and an optimal pH. In some way,
      all of the risk factors discussed impact either directly or indirectly with this
      basic molecular process. Once adherence is accomplished, potential pathogens may
      begin to colonize the respiratory tract. Once colonization occurs, bacteria may
      proliferate on the respiratory mucosa. At this point, the general status of host
      defenses determines whether colonization progresses to overt parenchymal lung
      infection.

PMID- 8885060
TI  - Microbial causes of ventilator-associated pneumonia.
AB  - Aspiration of microorganisms colonizing the oropharynx is the main route of
      bacterial entry to lower airways in mechanically ventilated patients. Examination
      of the microbial flora involved in ventilator-associated pneumonia shows that
      only few species, among the many oropharynx microorganisms, are responsible for
      the majority of lower respiratory tract colonizations and infections in intubated
      patients. Underlying disease, length of intubation, and type and duration of
      prior antibiotic therapy are the most important factors related with the
      causative flora of respiratory infections in these patients. Except in certain
      populations (eg, chronic obstructive pulmonary disease [COPD] patients who may be
      colonized by Pseudomonas aeruginosa), methicillin-sensitive Staphylococcus
      aureus, Streptococcus pneumoniae, and unencapsulated Hemophilus influenzae are
      the predominant respiratory pathogens within the first week of intubation in
      critically ill patients. These microorganisms are subsequently replaced by
      multiresistant flora, such as Pseudomonas aeruginosa, methicillin-resistant
      staphylococci or Acinetobacter baumanii. This change of flora takes place as a
      consequence of prior antibiotic therapy among other factors. Fungi have to be
      taken in account particularly in the presence of severe immunodepression. All of
      these multiresistant pathogens (particularly P aeruginosa) are responsible for
      most of the deaths directly related to pneumonia; therefore, the early
      recognition of causative agents and appropriate antibiotic therapy are of great
      importance determining outcome. This strategy represents the most efficient
      approach to managing patients with ventilator-associated pneumonia.

PMID- 8885061
TI  - Nosocomial pneumonia in mechanically ventilated adult patients: epidemiology and
      prevention in 1996.
AB  - Mechanically ventilated patients have a higher incidence of pneumonia and
      mortality than do nonventilated patients. Ventilator-associated pneumonia (VAP)
      is diagnosed clinically, by bronchoscopy or "blind" bronchoalveolar lavage (BAL)
      or protected specimen brush (PSB), and by quantitative endobronchial aspirates
      (QEA). VAP is usually caused by bacteria, but Legionella pneumophila,
      Mycobacterium tuberculosis, viruses, and fungi are also potential pathogens.
      Bacteria causing nosocomial pneumonia may be part of the patient's endogenous
      flora, originate from other patients, hospital personnel, or environmental
      sources. Pseudomonas aeruginosa, Acinetobacter spp, and Staphylococcus aureus are
      the most common causative agents in late-onset nosocomial pneumonia, and
      Streptococcus pneumoniae and Hemophilus influenzae are more commonly found in
      early-onset pneumonia. Aspiration appears to be the major route for the entry of
      bacteria into the lower respiratory tract. Host factors, oropharyngeal and
      gastric colonization, cross-infection, and complications from the use of
      antibiotics and nasogastric and endotracheal tubes increases the risk of
      bacterial VAP. A working knowledge of the epidemiology and strategies for
      prevention of VAP should reduce infection rates, morbidity, and mortality in
      critically ill patients.

PMID- 8885062
TI  - Histology and microbiology of ventilator-associated pneumonias.
AB  - A good knowledge of histological and bacteriological characteristics of
      experimental and human ventilator-associated bronchopneumonias (BPN) is of
      critical importance for the intensivist. BPN can be experimentally produced by
      intratracheal inoculation of microorganisms in high concentrations and ventilator
      associated BPN by ventilating baboons with oleic-acid lung injury. Experimental
      ventilator-associated BPN is frequently polymicrobial, and bacterial lung burden
      increases with the severity of lung infection. In human ventilator-associated
      BPN, gross examination is of poor value for diagnosing lung infection. Four
      histologic categories of increasing severity have been described: bronchiolitis,
      focal bronchopneumonia, confluent bronchopneumonia, and lung abscess. Nonspecific
      inflammatory lesions are always associated with histologic lung infection:
      primary lung infection causes secondary inflammatory lung damage, whereas non
      specific alveolar injury is rapidly superinfected when the lungs are mechanically
      ventilated. Infectious pulmonary lesions are disseminated within all pulmonary
      segments but preferentially found in the dependent segments. This fact suggests
      that ventilator-associated BPN has a bronchogenic origin and that gravity plays
      an important role in the dissemination of microorganisms within lung parenchyma.
      Ventilator-associated BPN is a nosocomial infection with a predominance of gram
      negative bacteria, staphylococci species, and yeasts. It is frequently
      polymicrobial, and the lung bacterial burden depends on the histologic grade, the
      administration of topical and intravenous antibiotics, and the host's local
      antibacterial defenses. The bacterial complexity of human lung infection does not
      support the concept of a threshold for the diagnosis of nosocomial BPN.
      Intensivists should always keep in mind that human ventilator-associated BPN is a
      complex and rapidly changing entity.

PMID- 8885063
TI  - Every person infected with HIV-1 should be in a lifelong early intervention
      program.

PMID- 8885064
TI  - Self-medication and STD prevention.

PMID- 8885065
TI  - Predictors of condom use and human immunodeficiency virus test seeking among
      women living in inner-city public housing developments.
AB  - BACKGROUND AND OBJECTIVES: To examine prevalence and predictors of condom use and
      human immunodeficiency virus (HIV) test seeking among women living in inner-city
      housing developments. STUDY DESIGN: Between April and June 1994, 671 women living
      in low-income housing developments in five cities in the United States completed
      an anonymous self-report questionnaire eliciting information on acquired immune
      deficiency syndrome (AIDS) risk behavior and characteristics indicative of risk.
      RESULTS: Most participants were women of color who were economically
      disadvantaged. Fifteen percent reported multiple sex partners, and 30% of women
      with one sex partner believed he had sex with someone else in the past year.
      Predictors of condom use included increased rates of safe-sex negotiation,
      stronger risk reduction intentions, absence of condom barrier beliefs, and
      multiple sex partners. Women tested for HIV in the past year were younger,
      perceived themselves to be at risk for HIV infection, reported more conversations
      with other women about AIDS concerns, and had condoms readily available.
      CONCLUSIONS: HIV public health prevention interventions are urgently needed for
      women who live in low-income urban housing developments.

PMID- 8885066
TI  - Comparison of methods for the detection of treponema pallidum in lesions of early
      syphilis.
AB  - BACKGROUND: The clinical diagnosis of primary and secondary syphilis can be
      difficult because of the wide variability of lesions. The available laboratory
      tests (dark-field microscopy and direct fluorescent antibody) require specialized
      microscopes and skilled technicians, and serologic tests are insensitive in early
      infection. METHODS: Dark-field microscopy and monoclonal antibody staining were
      compared to a new solid-phase enzyme-linked immunosorbent assay (Visuwell test)
      for detection of T. pallidum in lesion exudate of 188 patients with genital
      lesions. RESULTS: Sixty-four patients (34%) had lesions of early syphilis
      diagnosed by either dark-field, monoclonal antibody staining, or both. The
      Visuwell test and dark-field examination were positive in 52 (81.3%) and 55
      (85.9%) of the 64 patients, respectively, whereas the monoclonal antibody
      staining technique demonstrated the presence of T. pallidum in 59 (92.2%) of the
      64 patients. The Visuwell test gave a negative result in 111 of 124 patients who
      had negative dark-field and direct fluorescent antibody test results (89.5%
      specificity). CONCLUSIONS: The Visuwell test is an alternative method for
      evaluating genital ulcers but is less sensitive and specific than existing tests.

PMID- 8885067
TI  - Early intervention for human immunodeficiency virus in Baltimore Sexually
      Transmitted Diseases Clinics. Impact on gonorrhea incidence in patients infected
      with HIV.
AB  - BACKGROUND: High incidences of sexually transmitted diseases (STD) after posttest
      counseling have been documented in patients diagnosed with human immunodeficiency
      virus (HIV) in Baltimore STD clinics. In July 1991, the authors instituted an HIV
      early intervention program providing long-term medical care and social work
      services. This study compares the incidence of gonorrhea after post-HIV+ test
      counseling in patients diagnosed with HIV before and after the institution of the
      early intervention program. METHODS: Medical records of a cohort composed of all
      patients newly diagnosed with HIV and those who underwent posttest counseling for
      HIV in 1991 to 1993 in two Baltimore STD clinics were reviewed. Patients were
      offered early intervention medical and social work services. Gonorrhea incidence
      in this cohort was compared to a historical cohort diagnosed and counseled for
      post-HIV+ testing in 1988 to 1989 who were not offered early intervention
      services. RESULTS: The mean follow-up time was 418 days (range, 26 to 703 days).
      After post-HIV+ test counseling, gonorrhea developed in 39 of 468 (8.3%) men in
      the 1989 cohort and 13 of 400 (3.3%) men in the 1991 to 1993 cohort. Controlling
      for variable length of follow-up, the 1991 to 1993 cohort had a relative risk of
      0.442 for the development of gonorrhea during the study period (95% confidence
      interval, 0.225 to 0.790; P = 0.006). Incident gonorrhea after post-HIV+ test
      counseling also was associated with a prevalent gonorrhea condition at the time
      of HIV diagnosis (RR = 3.02; 95% CI, 1.75 to 5.23; P = 0.0001) and failure to
      return for post-HIV+ test counseling as scheduled (RR = 2.27; 95% CI, 1.17-4.43;
      P = 0.013). After adjustment for gonorrhea at the time of HIV diagnosis and
      failure to return for scheduled posttest counseling, the difference in gonorrhea
      incidence between men in the two cohorts remained statistically significant (RR =
      0.494; 95% CI, 0.260 to 0.941; P = 0.032). In comparison, overall gonorrhea rates
      in Baltimore changed little between 1988 and 1993. No significant difference was
      found in gonorrhea incidence in women, which may have been the result of active
      gonorrhea screening during the 1991 to 1993 period, which was not performed in
      1988 to 1989. CONCLUSIONS: Providing clinical care to persons with HIV may
      facilitate the reduction of high-risk behaviors that lead to incident STDs and
      further HIV transmission.

PMID- 8885068
TI  - Tetracycline-resistant Neisseria gonorrhoeae. Characteristics of patients and
      isolates at a London Genitourinary Medicine Clinic.
AB  - OBJECTIVES: To compare auxotypes, serovars, and antibiograms of tetracycline
      resistant Neisseria gonorrhoeae (TRNG) and non-TRNG isolated from patients
      attending an East London Genitourinary Medicine (GUM) Clinic. To obtain plasmid
      profiles for penicillinase-producing gonococci (PPNG) as well as presumptive
      TRNG. To identify differences in patient characteristics for the TRNG and non
      TRNG patient groups. STUDY DESIGN: Gonococcal isolates were collected from 400
      patients attending the GUM clinic at the Royal London Hospital GUM Clinic over a
      1-year period. Isolates (378) were tested for susceptibility to various
      antibiotics, auxotyped, and serotyped. Plasmid profiles were obtained for PPNG
      and isolates exhibiting high-level tetracycline resistance (TRNG). The presence
      of the tet M determinant was confirmed using the polymerase chain reaction (PCR).
      The PCR product was digested with the restriction endonuclease (RE) Hpa II and
      electrophoresed on a 2.5% agarose gel to determine an "RE pattern." Patient data
      were collected by retrospective case-note review. RESULTS: TRNG (n = 42)
      accounted for 11% of the 378 isolates tested, and the remaining 336 (89%)
      isolates were non-TRNG. Non-requiring auxotrophy and P1B-2 serovar expression
      occurred more frequently among TRNG. PPNG accounted for 31% of TRNG and 5% of non
      TRNG. Chromosomal resistance to penicillin (CMRNG) was absent among TRNG but
      accounted for 11% of non-TRNG. One TRNG isolate showed decreased susceptibility
      to ciprofloxacin (MIC 0.25 mg/l). All isolates were sensitive to cefotaxime,
      cefixime, spectinomycin, and azithromycin. All TRNG possessed the 25.2 MDa
      plasmid and produced a PCR product of appropriate size after tet M gene sequence
      amplification. RE digests of the PCR product gave a single pattern. None of the
      TRNG in contrast to 18% of the non-TRNG were acquired homosexually. Ethnic
      distribution differed between the patients with TRNG and patients without non
      TRNG (Afro-Caribbean 81% versus 58%; white 19% versus 36%). Most TRNG were
      acquired in the United Kingdom. CONCLUSIONS: TRNG differ from the non-TRNG in
      their auxotype and serovar distribution. PPNG are more common among the TRNG
      isolates, whereas CMRNG appear absent. TRNG are isolated more commonly from Afro
      Caribbean patients and were not represented among homosexually acquired isolates.

PMID- 8885069
TI  - Decreasing incidences of gonorrhea- and chlamydia-associated acute pelvic
      inflammatory disease. A 25-year study from an urban area of central Sweden.
AB  - BACKGROUND AND OBJECTIVES: Acute pelvic inflammatory disease (PID) affects women
      in their reproductive years and is often a complication of a sexually transmitted
      disease (STD), particularly Neisseria gonorrhoeae and Chlamydia trachomatis.
      Infertility, ectopic pregnancy, and chronic lower abdominal pain are common long
      term sequelae to acute PID. Through different preventive measures, endemic N.
      gonorrhoeae is almost eliminated, and C. trachomatis has been reduced almost
      fourfold in Sweden. GOALS: To investigate variations in STD-associated acute PID
      and the extent to which this influenced the yearly incidences of patients
      hospitalized for this complication during a 25-year-period. STUDY DESIGN:
      Hospital records of 2499 patients admitted and treated for acute PID from January
      1, 1970 to December 31, 1994 were analyzed for infection with N. gonorrhoeae.
      Routine laboratory diagnosis for C. trachomatis infection started June 1, 1980.
      Detailed statistical analysis for chlamydial-associated PID in this study,
      therefore, covers the period January 1, 1981 to December 31, 1994 and includes
      1030 patients. RESULTS: Gonorrhea occurred in 42% of patients with acute PID in
      1970 and decreased continuously to zero in 1988 and beyond. Concomitant
      urogenital chlamydial infection reduced almost fourfold from 28.4% in 1985 to
      7.7% in 1994. Yearly admissions for acute PID fluctuated slightly (< or = 16%) in
      the early 1970s and early 1980s but increased greatly (> 60%) in the middle and
      late 1970s; the highest was 180 per year in 1976. This coincided with high
      incidence rates of gonorrhea in the general population, and probably of genital
      C. trachomatis infection as well, coupled with an increased use of intrauterine
      contraceptive device in nulliparous women. The largest increase in admissions for
      acute PID was in the 15- to 29-year-old group. A steady decrease started in 1987
      and reached the low figure of 26 admissions in 1994. The greatest decrease
      occurred in the 15- to 19-year-old group, from the relative age distribution of
      28.9% in the period 1970 to 1974 to 12.9% in 1990 to 1994. Yearly admissions for
      the > or = 35-year-old group remained almost constant during the study period,
      but the relative age distribution shifted from second lowest (excluding those 14
      years or younger, totaling 15 admissions for the entire study period), 9.1% at
      the beginning of the study period, to the second largest, 24.9% at the end of it.
      The study also showed that the total and relative rates of recurrence decreased.
      CONCLUSIONS: Measures aimed at reducing incidences of gonorrhea and genital
      chlamydial infection will reduce the incidences of one of the most serious
      complications of these STDs, acute PID, and, in turn, its long-term sequelae.

PMID- 8885070
TI  - Finding neurosyphilis without the Venereal Disease Research Laboratory test.
AB  - BACKGROUND: The cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory
      (VDRL) test is only 27% sensitive for diagnosing neurosyphilis. Discriminant
      analysis, used on 124 patients, shows that other commonly used laboratory tests
      can, in combination, identify 87% of patients with neurosyphilis with 94%
      specificity. STUDY DESIGN: The insensitivity of the CSF-VDRL (27% in persons with
      neurosyphilis) and the foreseen greater need to identify and treat neurosyphilis
      in the era of human immunodeficiency virus caused us to analyze the serum and
      cerebrospinal fluid results of 73 patients with syphilis and of 51 patients with
      clinically diagnosed neurosyphilis. Discriminant analysis was applied to
      different sets of laboratory tests to find the combination of test results best
      able to predict retrospectively the clinical diagnosis of syphilis or
      neurosyphilis, without reference to the CSF-VDRL. RESULTS: The predicting
      function averages 94% specificity and 87% sensitivity. Test result variables
      considered together are: CSF-FTA-ABS, serum FTA-ABS, CSF-TPHA, serum TPHA, and
      CSF cells. CONCLUSIONS: The authors conclude that clinicians or laboratories can,
      independently of the CSF-VDRL, compute a score showing whether the results of a
      set of commonly used tests suggest neurosyphilis in a patient.

PMID- 8885071
TI  - Sexual intercourse during menstruation and self-reported sexually transmitted
      disease history among women.
AB  - OBJECTIVES: The purpose of this study was to examine the practice of sexual
      intercourse during menstruation and the relationship of this practice to the
      experience of sexually transmitted diseases (STD) among women in the United
      States. METHODS: Logistic regression technique was used to conduct an analysis of
      population-based data from a national sample of 1586 sexually active 20- to 37
      year-old women to examine the patterns of sexual intercourse during menstruation
      and its relationship with STD outcome. RESULTS: More than one fourth of the women
      reported that they usually have vaginal intercourse during their menses, and 16%
      reported that they had had vaginal intercourse during their last menstrual
      period. Proportions of women engaging in this practice were higher among those
      who reported greater frequency of intercourse and larger numbers of lifetime sex
      partners. Almost half the women who had intercourse more than twice a week and
      more than one third of the women who had more than seven lifetime sex partners
      reported that they usually have vaginal intercourse during menses. The findings
      suggest that this practice is relatively more common among the better educated,
      young, white women and their sex partners. Most interestingly, despite the fact
      that sex during menses is most common among women in relatively low-risk groups,
      we were able to observe a strong statistical association between sexual
      intercourse during menstruation and self-reported STD history. CONCLUSIONS:
      Sexual intercourse during menstruation may emerge more consistently as a risk
      factor for the heterosexual transmission of HIV or other sexually transmitted
      pathogens in future studies. If future epidemiologic studies continue to bolster
      this finding, then public health efforts should promote abstinence during the
      female menstrual period and target those groups of women among whom this practice
      is prevalent.

PMID- 8885072
TI  - Urine as a diagnostic specimen for the detection of Chlamydia trachomatis in
      Malaysia by ligase chain reaction.
AB  - BACKGROUND AND OBJECTIVES: Noninvasive urine screening for Chlamydia trachomatis
      infections offers a valuable public health tool, which could be of vast
      importance in chlamydial control programs. The authors evaluated a new DNA
      amplification method, ligase chain reaction (LCR). GOALS: The goal was to
      ascertain whether urine testing could be used as screening method to detect C.
      trachomatis infections in commercial sex workers, patients at sexually
      transmitted diseases clinic, and asymptomatic patients in Kuala Lumpur, Malaysia.
      METHODS: First-void urine specimens from 300 men and 300 women were tested by
      LCR, as well as by a commercially available enzyme immunoassay. The LCR assay
      amplifies specific sequences within the chlamydial plasmid with ligand-labeled
      probes, and the resultant amplicons are detected by an automated immunoassay.
      Specimens with discrepant results were confirmed by another LCR of the specimen
      that targeted the gene for the major outer membrane protein (OMP1). RESULTS:
      There were 31 LCR-positive male urine and 37 LCR-positive female urine specimens.
      The resolved sensitivity and specificity for the LCR of the male urine specimens
      were 100% and 99.6%, respectively, whereas for female urine specimens, the
      sensitivity and specificity were 100% and 98.5%, respectively. After resolution
      of discrepant test results by OMP1 LCR, the prevalence was 10% for men and 11%
      for women. The urine enzyme immunoassay was not useful in diagnosing C.
      trachomatis infections in either men or women, as the resolved sensitivities were
      10% and 15.2%, respectively. The specificities were 99.6% for men and 98.9% for
      women. CONCLUSIONS: Testing first-void urine specimens by LCR is a highly
      sensitive and specific method to diagnose C. trachomatis infections in men and
      women, providing health care workers and public health officials with a new
      molecular amplification assay that uses noninvasive urine specimens for
      population-based screening purposes.

PMID- 8885073
TI  - Antibiotic prophylaxis among commercial sex workers in Cebu City, Philippines.
      Patterns of use and perceptions of efficacy.
AB  - BACKGROUND: This study describes the extent to which commercial sex workers (CSW)
      in Cebu City, Philippines perceive prophylactic antibiotic use to be an effective
      form of prevention for sexually transmitted diseases (STD) and human
      immunodeficiency virus (HIV), as well as the prevalence of this self-treatment
      practice. METHODS: A survey instrument was developed and pretested after 3 months
      of intensive ethnographic research on STD and acquired immune deficiency syndrome
      (AIDS). A multistage sampling procedure was followed to ensure that a
      representative sample of CSW from four distinct work environments would be
      interviewed. Commercial sex workers registered at the Cebu City social hygiene
      clinic were sampled randomly from coded work establishment lists, and a
      convenience sample of unregistered freelance CSW was secured. In total, 200 CSW
      were interviewed. Of these 200 CSW, all were sexually active, but only 160 had
      been engaged actively in commercial sexual exchange the month before their
      interviews. RESULTS: Popular use of antibiotics as prophylaxis against STD is
      commonplace in the Philippines among CSW, with 38% reporting routine or
      occasional use and 31% reporting use in the last 2 weeks. Unregistered CSW are
      five times more likely to use prophylactic antibiotics than registered CSW, and
      they are seven times less likely to use condoms with 80% or more of their
      customers. They also have sex with three times as many customers. CONCLUSIONS:
      Use of prophylactic antibiotics by CSW offers them a false sense of security in a
      high-risk work environment. Self-treatment with low-dose prophylactic antibiotics
      provides no protection against STD, impedes STD screening efforts, and
      contributes to antibiotic resistance. An alarming percentage of CSW consider
      antibiotics a potential means of protecting themselves against AIDS. Public
      health interventions focusing on STD and AIDS in developing countries must
      address current patterns of prophylactic antibiotic use.

PMID- 8885074
TI  - Nonoxynol-9 in lubricated condoms. Results of a study in female prostitutes.
AB  - BACKGROUND AND OBJECTIVES: Debate continues on the efficacy and safety of
      intravaginal nonoxynol-9 for the prevention of horizontal transmission of human
      immunodeficiency and other sexually transmitted diseases. Little attention has
      been paid to the effects of nonoxynol-9 contained in the lubricant of many
      condoms. GOAL: To assess the tolerability of different levels of nonoxynol-9 in
      condom lubricants. STUDY DESIGN: Pilot, randomized, controlled trial in 70 female
      prostitutes. RESULTS: There was no association between dose of nonoxynol-9 and
      reported symptoms or signs of genital tract inflammation; an increased dose of
      nonoxynol-9 was associated with increased numbers of polymorphonuclear leukocytes
      on a vaginal wall smear. CONCLUSIONS: There is no recognized simple method of
      defining inflammation in the female genital tract. Future studies of the effects
      of low-dose nonoxynol-9 on the female genital tract require highly controlled
      exposures, plus colposcopy with or without vaginal biopsy to define inflammation.

PMID- 8885075
TI  - Epidemiology of trichomonas vaginalis. A prospective study in China.
AB  - BACKGROUND AND OBJECTIVES: Trichomonas vaginalis infection is probably one of the
      most common sexually transmitted diseases. The epidemiology of this disease has
      long been ignored, and not much is known about its natural history and risk
      factors. GOALS: The authors conducted this study to define the incidence rates of
      T. vaginalis infection and to investigate risk factors for the infection. STUDY
      DESIGN: A prospective study was carried out on a cohort of 16,797 women followed
      up from 1974 to 1985 within the framework of a cervical screening program in
      Jingan, China. Personal interviews were conducted by trained interviewers.
      RESULTS: A total of 1489 new cases of T. vaginalis infection were diagnosed with
      132,946 person-years of observation. In a multivariate analysis, the increased
      risk was associated with multiple sexual partners (P = 0.0124) and greater number
      of induced abortions (P = 0.0028). The relative risks were 1.3 (95% confidence
      interval [CI], 1.1 to 1.5) for smokers and 1.5 (95% CI, 1.2 to 2.0) for those who
      drink alcohol. An inverse relationship was observed in older women and in women
      with cervical atrophy. CONCLUSIONS: This study confirmed the relationship between
      T. vaginalis and multiple sexual partners and suggests that the risk for T.
      vaginalis also may be related to life-style risk factors.

PMID- 8885076
TI  - Quinolone-resistant Neisseria gonorrhoeae isolated in Sydney, Australia, 1991 to
      1995.
AB  - BACKGROUND AND OBJECTIVES: Quinolone antibiotics are used widely for the
      treatment of gonorrhea, but resistant strains appeared in Sydney in 1984,
      treatment failure with high-dose regimens in 1991, and isolates with very high
      minimal inhibitory concentrations (MICs) (16 mg/l) in 1994. GOALS: To examine the
      frequency, source, and characteristics of Quinolone-resistant Neisseria
      gonorrhoeae (QRNG) in Sydney from 1991 to 1995 and to compare these data with
      those obtained from 1984 to 1990. STUDY DESIGN: The antibiotic sensitivity,
      auxotype-serovar class, and geographic source of QRNG isolated in Sydney from
      January 1, 1991 to June 30, 1995 were analyzed. RESULTS: One hundred seven QRNG
      were isolated from 97 patients from 1991 to 1995. The number, proportion, and
      MICs of QRNG increased slowly in the first 4 years of the study and rapidly in
      the last 6 months. Most QRNG were isolated from travelers entering Sydney from
      Asia. Twenty-seven different auxotype-serovar classes were detected including 6
      auxotype-serovar classes in 14 isolates with high-level quinolone resistance
      (MIC, 16 mg/l). CONCLUSIONS: QRNG isolated in Sydney during the past decade
      originated in Asia as multiple gonococcal subtypes and increased substantially in
      numbers and levels of resistance in 1995.

PMID- 8885077
TI  - The causal role for genital ulcer disease as a risk factor for transmission of
      human immunodeficiency virus. An application of the Bradford Hill criteria.
AB  - BACKGROUND AND OBJECTIVES: Genital ulcer disease (GUD) has been reported to
      increase the risk for the acquisition of human immunodeficiency virus (HIV).
      Although many investigators have reported an increased risk for HIV infection in
      persons with concurrent or previous GUD, not all studies have been designed to
      determine whether GUD causes an increased risk for HIV infection or acts only as
      a risk marker for infection. The evidence from the literature is discussed, and
      the criteria for causal inference proposed by Sir Austin Bradford Hill are
      applied. GOAL: To evaluate the strength of the association between GUD and
      infection by HIV. STUDY DESIGN: Case-control, cross-sectional, and cohort studies
      that examined the association between HIV seroconversion and GUD were chosen from
      the literature. Twenty-seven epidemiologic studies were selected for analysis,
      many of which reported separate analyses of the association between HIV infection
      and herpes simplex virus infection, syphilis, or nonspecified GUD. The studies
      were analyzed to investigate the magnitude of association between GUD and HIV,
      and the evidence evaluated using Hill's criteria. RESULTS: Approximately two
      thirds of the analyses reported a statistically significant association between
      GUD and HIV infection. Fourteen studies reported 29 separate analyses using a
      case-control design, 18 of which reported a statistically significant association
      between GUD (GUD, herpes, and syphilis) and HIV infection, four analyses were of
      varying significance depending on the analytical technique used, and seven were
      nonsignificant. Thirteen studies reported 23 separate longitudinal analyses that
      used a nested case-control or cohort design: 11 reported a significant
      association, 11 had nonsignificant findings, and results of one study varied. No
      study reported a statistically significant negative association. When applying
      the literature to Hill's criteria, all nine criteria for causal inference were
      met, providing additional evidence that genital ulcers are associated with an
      increased risk for the development of HIV infection. CONCLUSIONS: The published
      evidence suggests that GUD increases the risk for HIV acquisition. Few studies,
      however, have examined carefully the temporal association between preexisting GUD
      and subsequent HIV acquisition. The analyses that simultaneously controlled for
      additional risks for HIV infection, such as lifetime sex partners or history of
      injection drug use, report a generally lower risk for HIV associated with GUD. It
      is likely that studies that adequately control for risk factors will find a lower
      risk associated with GUD than was reported in the literature earlier in the HIV
      epidemic. Future research needs and the problems associated with conducting these
      types of studies are discussed.

PMID- 8885078
TI  - Cost-effectiveness of contact tracing versus screening to find syphilis cases:
      further study is needed.

PMID- 8885079
TI  - Oxidants augment endotoxin-induced activation of alveolar macrophages.
AB  - Endotoxin (lipopolysaccharide) stimulation of macrophages (M phi) induces the
      generation of toxic reactive oxygen intermediates (ROI); however, recent studies
      implicate intracellular redox changes in signal transduction pathways for
      cytokines. To test whether oxidant stress modulates M phi activation, rabbit
      alveolar M phi were exposed to the following: diamide (oxidizes intracellular
      glutathione); glucose oxidase (generates hydrogen peroxide); or xanthine oxidase
      (generates superoxide), before lipopolysaccharide. Supernatants were assayed for
      tumor necrosis factor (TNF) and cell lysates were assayed for procoagulant
      activity (PCA). TNF mRNA was analyzed by Northern blot. M phi exposure to diamide
      and glucose oxidase augmented TNF production, PCA expression, and TNF mRNA
      accumulation; however, xanthine oxidase exposure inhibited TNF production while
      augmenting PCA expression. M phi signal transduction can be enhanced by
      increasing cellular oxidant stress. The differential response of TNF versus PCA
      suggests the existence of distinct redox-sensitive signal transduction pathways.
      These data define a mechanism by which oxidants generated during inflammation may
      modulate M phi function.

PMID- 8885080
TI  - Endotoxin-induced alterations in insulin-stimulated phosphorylation of insulin
      receptor, IRS-1, and MAP kinase in skeletal muscle.
AB  - Sepsis and endotoxin (LPS) have been demonstrated to impair insulin-mediated
      glucose uptake in skeletal muscle. However, the intracellular mechanism
      responsible for this defect is not fully defined. The purpose of the present
      study was to determine whether specific elements of the insulin receptor (IR)
      signaling pathway in skeletal muscle are altered by LPS. In vivo injection of
      Escherichia coli LPS resulted in a 44% reduction in whole body glucose disposal
      under euglycemic hyperinsulinemic conditions, which was largely accounted for by
      a decreased rate of glycogen synthesis. Scatchard analysis indicated that the
      number and affinity of the high-affinity insulin binding sites in muscle were
      similar between control and LPS-treated rats. Western blot analysis indicated
      that under basal conditions, the levels of total and phosphorylated IR, insulin
      receptor substrate (IRS)-1, and mitogen-activated protein (MAP) kinase were not
      significantly different between control and endotoxic rats. In control animals,
      muscle obtained 2 min after intravenous injection of a maximally stimulating dose
      of insulin demonstrated a marked increase in the amount of phosphorylated IR
      (approximately 5-fold), IRS-1 (approximately 10-fold), and MAP kinase
      (approximately 10-fold). Insulin-stimulated phosphorylation of IR, IRS-1, and MAP
      kinase was markedly diminished (approximately 75%, 90%, and 78%, respectively) in
      LPS-treated rats. However, there was no concomitant reduction in the total
      abundance of these proteins under hyperinsulinemic conditions. These data
      demonstrate that LPS alters multiple steps in the insulin signal transduction
      pathway, but not insulin binding, in skeletal muscle that may mediate the
      observed impairment in glucose uptake.

PMID- 8885081
TI  - Visceral ischemia-reperfusion injury promotes tumor necrosis factor (TNF) and
      interleukin-1 (IL-1) dependent organ injury in the mouse.
AB  - Acute visceral ischemia and subsequent reperfusion injury, which accompanies the
      surgical repair of a thoracoabdominal aorta aneurysm, is associated with high
      rates of morbidity and mortality. The purpose of the present study was to
      determine whether endogenous tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1 (IL-1) production contributes to organ dysfunction in animals
      subjected to visceral ischemia secondary to 30 min of supraceliac aortic
      occlusion. C57BL6/j mice were treated with either a TNF binding protein (TNF-bp
      10 mg/kg) or an anti-IL-1 receptor type 1 antibody (150 micrograms) 2 h prior to
      30 min of supraceliac aortic occlusion. An additional group of mice received 30
      min of infrarenal aortic occlusion to determine the contribution of lower torso
      ischemia-reperfusion injury to the changes seen following supraceliac aortic
      occlusion. Visceral organ ischemia for 30 min produced by supraceliac aortic
      occlusion followed by 2 h of reperfusion produced measurable TNF-alpha in 38% of
      untreated mice, but TNF-alpha was undetectable in both sham-operated mice and
      following infrarenal aortic occlusion. After 2 h of reperfusion, lung
      myeloperoxidase levels were significantly elevated in the mice experiencing
      visceral ischemia-reperfusion compared with either a sham operation or infrarenal
      ischemia-reperfusion (11.6 +/- 1.3 U/g vs. 3.4 +/- .2 U/g and 3.7 +/- 1.0 U/g,
      respectively, p < .05). Pretreatment with TNF-bp and anti-IL-1 antibody decreased
      lung neutrophil recruitment (7.2 +/- 1.2 U/g and 4.6 +/- 1.1 U/g) and capillary
      membrane permeability changes in mice following visceral ischemia-reperfusion.
      The present study demonstrates that brief (30 min) clinically relevant visceral
      ischemia produces TNF-alpha and IL-1 dependent lung injury.

PMID- 8885082
TI  - Time course of endothelial dysfunction and neutrophil adherence and infiltration
      during murine traumatic shock.
AB  - Traumatic shock in rats has been shown to induce endothelial dysfunction, and to
      increase intestinal myeloperoxidase activity (MPO) indicative of neutrophil
      infiltration. To examine the time course of endothelial dysfunction and
      neutrophil adherence and infiltration, pentobarbital anesthetized rats, subjected
      to Noble-Collip drum trauma, were studied prior to and 15, 30, 60, 90, 120, 150,
      and 180 min following drum trauma. Superior mesenteric artery rings obtained from
      traumatized rats were tested for responsiveness to acetylcholine (ACh), a
      receptor-mediated endothelium-dependent vasodilator, and to NaNO2 an endothelium
      independent vasodilator. ACh-induced relaxation was not impaired immediately
      after the induction of trauma (time 0). However, 15-30 min after trauma,
      responses to ACh were significantly depressed (p < .05) and were further reduced
      (p < .01) 90-180 min after trauma. No significant changes occurred in response to
      the direct vasodilator NaNO2 at any of the times studied, indicating no vascular
      smooth muscle injury. Moreover, the adherence of polymorphonuclear leukocytes
      (PMNs) to the post-traumatic mesenteric vascular endothelium also showed an
      increase that peaked 30 min post-trauma. Intestinal MPO activity, indicative of
      neutrophil infiltration, was characterized by a continuous and sustained increase
      from 30-180 min. Our findings suggest that endothelial dysfunction resulting in
      reduced NO release occurs in the early phase of murine traumatic shock, and that
      this phenomenon is followed by a time-dependent increase in adhesivity of
      neutrophils to the vascular endothelium leading to a progressive accumulation of
      PMNs in injured tissues (e.g., intestine).

PMID- 8885083
TI  - Thromboxane rather than platelet activating factor mediates pulmonary
      vasoconstriction after antigen challenge in rabbits.
AB  - To investigate whether thromboxane and/or platelet activating factor (PAF)
      mediate the pulmonary vasoconstrictive response to antigen in vivo, we intra
      arterially injected human erythrocytes as antigen into sensitized rabbits after
      administration of putative inhibitors: a cyclooxygenase synthetase inhibitor
      (indomethacin, 5 mg.kg-1), a thromboxane synthetase inhibitor (OKY 046, 10 mg.kg
      1 + 100 micrograms.kg-1.min-1), and a PAF blocker (CV6209, .1 mg.kg-1). Pulmonary
      artery and airway pressures significantly increased after the antigen challenge
      in sensitized rabbits, but did not in nonsensitized rabbits. Both indomethacin
      and OKY046 significantly inhibited the increase in pulmonary artery pressure
      after the antigen challenge, while CV6209 did not. CV6209 significantly
      attenuated the decrease in femoral artery pressure after the antigen challenge,
      while neither indomethacin nor OKY046 did. There were no significant differences
      in the increase in airway pressure among the groups. We conclude that thromboxane
      rather than PAF mediates the pulmonary vasoconstriction after the antigen
      challenge and that mediators other than thromboxane and PAF mediate
      bronchoconstriction after the antigen challenge in sensitized rabbits.

PMID- 8885084
TI  - Splanchnic homeostasis during endotoxin challenge in the pig as assessed by
      microdialysis and tonometry.
AB  - The splanchnic region is particularly susceptible to shock. The purpose of this
      study was to evaluate microdialysis of the liver and small intestine as a monitor
      of splanchnic metabolic deterioration (elevation of lactate and hypoxanthine) in
      porcine endotoxic shock. Tonometry of the small intestine was used as a
      reference. Microdialysis probes (liver, ileum, and artery), tonometer, and
      pulmonary artery catheter were inserted. Eight animals were given Escherichia
      coli lipopolysaccharide endotoxin (20 micrograms kg-1 h-1 for 2 h). Five animals
      served as controls. Measurements were made every half-hour. Three hours after
      onset of endotoxin challenge, there were significant differences between
      endotoxin and control groups in intestinal lactate and hypoxanthine, as well as
      liver lactate, in addition to mucosal pH obtained by tonometry. Lactate elevation
      in blood was first seen at 4 h, while there was no significant hypoxanthine
      elevation in arterial blood over 5 h. Hence, data obtained from the splanchnic
      region became significantly different early, when compared with data obtained
      from arterial blood. Microdialysis of liver and small intestine as well as
      intestinal tonometry are sensitive tools for detection of splanchnic metabolic
      deterioration during endotoxin shock.

PMID- 8885085
TI  - Effects of L-canavanine, an inhibitor of inducible nitric oxide synthase, on
      endotoxin mediated shock in rats.
AB  - The effects of L-canavanine, an inhibitor of nitric oxide synthase, on endotoxin
      induced shock was investigated in the pentobarbitone anesthetized rat. Endotoxin
      infusion (2.5 mg kg-1 h-1 over 6 h) produced progressive and marked hypotension
      and hypoglycemia. Electron microscopy showed marked changes in the kidney,
      comprising severe endothelial cell disruption and the accumulation of platelets
      in the blood vessels. In the lung, there was marked accumulation of
      polymorphonuclear leukocytes in small blood vessels and endothelial disruption.
      Treatment with L-canavanine (10 mg kg-1 by bolus injection each hour starting 70
      min after endotoxin or saline infusion) significantly reduced endotoxin-induced
      hypotension, without any effect on the hypoglycemia. This treatment markedly
      reduced the endotoxin-induced electron microscopical changes in the kidneys and
      lungs. Although L-canavanine, like L-NAME, inhibited both cerebellar constitute
      and splenic inducible nitric oxide synthase in vitro, in contrast to L-NAME it
      did not modify either arterial blood pressure or carotid artery blood flow in
      control rats. The data are consistent with L-canavanine being a selective
      inhibitor of inducible nitric oxide synthase, at least in vivo, and suggest that
      inhibitors of this enzyme may be beneficial in endotoxin-induced shock.

PMID- 8885086
TI  - Effect of severe smoke inhalation injury on systemic microvascular blood flow in
      sheep.
AB  - Multiple nonpulmonary organ dysfunction is frequently associated with acute lung
      injury; however, the mechanisms underlying the pathogenesis of this process are
      not completely understood. Decreased oxygen delivery to distant organs due to
      maldistribution of blood flow may be a contributing factor. We examined the
      effects of acute lung injury induced by smoke inhalation on microvascular blood
      flow to various organs in sheep. Seven sheep were prepared with arterial, venous,
      pulmonary artery, and left atrial catheters. After a 5 day recovery period, a
      tracheostomy was performed, followed by insufflation with 48 breaths of cool
      cotton smoke. Determination of microvascular blood flow using colored
      microspheres, standard hemodynamic measures, and blood gas analysis were
      performed before and at 12 h intervals after smoke inhalation. Animals were
      resuscitated to maintain left atrial pressure at +/- 2 mmHg of the baseline value
      and FiO2 was adjusted to maintain Sao2 at > 90%. After 48 h, sheep were killed
      and an autopsy was performed. Samples of trachea, left ventricle, ileum, colon,
      spleen, pancreas, and cortex from both kidneys were obtained for determination of
      microvascular blood flow. Blood flow to the trachea was substantially increased,
      while blood flow to the kidneys was preserved near baseline levels. Left
      ventricular blood flow decreased slightly; however, this decline was not
      statistically significant. Blood flow to ileum, colon, spleen, and pancreas was
      significantly decreased, particularly at 36 and 48 h after injury. These
      decreases were independent of changes in cardiac output or systemic oxygen
      delivery. It is likely that alteration in microvascular blood flow may contribute
      to the development of nonpulmonary organ dysfunction after acute lung injury.

PMID- 8885087
TI  - The cardiopulmonary, eicosanoid, and tissue microanatomic effects of fluconazole
      during graded bacteremia.
AB  - Imidazole compounds have been shown to be beneficial in systemic sepsis and
      inflammation. The purpose of this study was to delineate the effects of
      fluconazole on systemic hemodynamics and on microanatomy of the heart, lung,
      liver, and kidney parenchyma of swine during graded bacteremia. Eighteen adult
      swine were studied in three groups: 1), anesthesia control; 2), septic control
      (Aeromonas hydrophila, 10(9)/mL, infused i.v. for 4 h); 3) fluconazole
      (fluconazole, 30 mg/kg i.v., followed by A. hydrophila infusion). After 4 h of
      graded bacteremia, autopsy was performed. Compared with the septic control group,
      cardiac index, oxygen delivery, and oxygen consumption were reduced significantly
      after fluconazole pretreatment, and mixed venous hemoglobin oxygen saturation
      (SVO2) and oxygen extraction were increased. Plasma thromboxane A2 and
      leukotriene levels were not affected by fluconazole. Computerized digital image
      analysis of the liver, heart, and kidney specimens revealed no statistically
      significant differences between the septic control group and fluconazole
      pretreated animals. In the lung specimens, preinfusion of fluconazole decreased
      alveolar wall thickness in septic swine (anesthesia control group: 8.15 x 10(-3)
      +/- 1.3 x 10(-3)mm versus septic control group: 9.9 x 10(-3) +/- 1.3 x 10(-4)
      versus fluconazole group: 6.8 x 10(-3) +/- 1.6 x 10(-3); p < or = .05).
      Fluconazole pretreatment before graded bacteremia has no beneficial effect on
      cardiopulmonary performance or septic tissue edema of the heart, kidney, or
      liver. Tissue oxygen metabolism might be down-regulated by fluconazole. However,
      preinfusion of fluconazole appears to normalize the sepsis-induced increase in
      pulmonary alveolar wall thickness. The net significance of these changes on
      clinical outcome is not clear from these data.

PMID- 8885088
TI  - Fluid-percussion brain injury adversely affects control of vascular tone during
      hemorrhagic shock.
AB  - To test the hypothesis that brain injury impairs control of vascular tone during
      compensation from hemorrhagic shock, Sprague-Dawley rats underwent fluid
      percussion brain injury (or sham injury control) followed by a stepwise
      hemorrhage period to 1/2 baseline mean arterial pressure (1/2 MAP), a shock
      period holding at 1/2 MAP for 30 min, and a resuscitation period. Aortic blood
      flow (ABF) was measured and vascular conductance (ABF/MAP) was calculated. No
      differences occurred between groups during the stepwise hemorrhage period. During
      the 30 min shock period, controls decreased conductance from .2 +/- .07 to .16 +/
      .04 and required repeated additional hemorrhage (3.4 +/- 1.3 cc) to maintain 1/2
      MAP. In contrast, brain-injured animals increased conductance from .21 +/- .07 to
      .24 +/- .06 (p < .05) during the shock period and required repeated fluid
      replacements (3.0 +/- 1.3 cc lactated Ringer's (LR), p < .05) to maintain 1/2
      MAP. Following resuscitation, conductance appropriately increased to .31 +/- .05
      in controls but did not change (.25 +/- .04, p < .05) in brain-injured animals.
      We conclude that brain injury adversely affects control of vascular tone during
      shock and resuscitation in this model.

PMID- 8885089
TI  - Acquired hyporesponsiveness to bacterial lipopolysaccharide and interferon-gamma
      in RAW 264.7 macrophages.
AB  - Bacterial lipopolysaccharide (LPS) can induce hyporesponsiveness to its own toxic
      effects, as reflected by the diminished production of tumor necrosis factor (TNF)
      and other inflammatory mediators by animals (and by purified macrophages) upon re
      challenge with LPS. We have examined the regulation of TNF and inducible nitric
      oxide synthase (iNOS) production in the murine macrophage cell line RAW 264.7.
      These cells accumulated TNF mRNA and secreted TNF protein in a dose-dependent
      fashion after exposure to either LPS or recombinant murine interferon-gamma (riFN
      gamma). Pre-exposure of RAW 264.7 cells to relatively high concentrations of LPS
      (> 10 ng/mL) resulted in diminished production of TNF in response to subsequent
      challenge with either LPS or riFN-gamma. In contrast, production of iNOS mRNA was
      either unaffected or augmented by pre-exposure of these cells to LPS. Our
      findings indicate that the hyporesponsive state of RAW 264.7 macrophages
      preincubated with LPS is not specific for LPS and that the production of TNF and
      nitric oxide (NO) by macrophages are differentially regulated.

PMID- 8885090
TI  - The effect of hypothermia on potassium and glucose changes in isobaric
      hemorrhagic shock in the rat.
AB  - Hypothermia has been shown to decrease oxygen consumption requirements and
      improve survival during hemorrhagic shock. however, hypothermia applied
      therapeutically does not prevent the development of a lactic acidosis during
      hemorrhage. We re-examined the development of a hemorrhage-induced lactic
      acidosis and other metabolic parameters (glucose, plasma electrolytes, and
      arterial blood gases) at various temperatures (29-37 degrees C) to better define
      the protective action of hypothermia in hemorrhagic shock. Five groups of male,
      Sprague-Dawley rats were bled to a mean arterial blood pressure (MABP) of 40 mmHg
      over a 15 min period and held there by further blood removal until death. The
      final level and rate of development of the lactic acidemia was the same in all
      groups. However, the rate of decline in plasma glucose and rate of rise in plasma
      potassium were temperature dependent. These results suggest that temperature
      dependent changes in serum glucose and potassium may contribute to the protective
      effect of hypothermia during hemorrhagic shock.

PMID- 8885091
TI  - On the value of clinical information. Is there a bridge between quantum theory
      and medical diagnosis?
AB  - This paper discusses the problems in assigning a precise value to an item (or
      group of items) of clinical information. Historical viewpoints are reviewed; the
      paper illustrates how determinist descriptive thinking has been overtaken by
      concepts of uncertainty and probability. Four equations are proposed outlining
      the factors which affect the value of clinical information. The validation of
      these equations and their implications is discussed. Parallels are drawn between
      the situation in theoretical physics a century ago and medical diagnostics today;
      and the central theme of uncertainty in both is emphasised. Finally, the need for
      further radical thinking is stressed.

PMID- 8885092
TI  - The acceptance of decision-support systems.

PMID- 8885093
TI  - Computer-aided classification of breast cancer nuclei.
AB  - Breast cancer is the most common malignancy affecting the female population in
      industrialized countries. Prognostic factors, such as steroid receptors
      visualized in biopsy slides, provide critical information to oncologists
      regarding the hormonal status of the individual tumors. These factors influence
      the choice of treatment and help in predicting patient survival and probability
      of recurrence. The objective of this paper is to introduce a new computer-aided
      system for the classification of breast cancer nuclei based on neural networks.
      Currently, medical experts assess steroid receptors in breast cancer biopsy
      slides mostly manually using four- or five-level grading schemes. These schemes
      are based on the assessment of two parameters: number of nuclei positive and
      their staining intensity. Available computerized systems define their own grading
      schemes based on automated measurements of low-level features, such as optical
      density, texture, area, and others. However, the findings produced by these
      systems may not be readily comprehensible by the majority of medical experts who
      have been accustomed to manual assessment schemes. Moreover, findings from one
      system cannot be directly compared to findings obtained from other computerized
      systems. To date, no standardized assessment scheme exists for computerized
      systems, while interobserver and intraobserver variabilities limit the utility of
      the routinely used manual assessment schemes. In this paper a new system for
      computer-aided biopsy analysis is introduced. Here, we focus on the system's
      nuclear classification module. The input to this module consists of a set of six
      local and global features: optical density, two chromaticity indices, a variance
      based texture measure, global nuclei density mean, and variance. The output of
      the nuclei classification module consists of a membership label in a zero to four
      grading scheme for each detected nucleus. The classification module is based on a
      feedforward neural network trained in a supervised fashion to classify the
      nuclear feature vectors. The sample data comprises 3015 nuclei from 28 images
      that were classified by a human expert. A Sammon plot visualization of the six
      dimensional input feature space shows that the classification problem is quite
      difficult. The neural network used in the classification module achieved 72%
      accuracy. Our result indicate that by using a nuclear classification module such
      as the one introduced in this paper it is possible to translate low-level system
      measurements into a vocabulary that is familiar to medical experts. Thus, a
      contribution is made to the standardization of grading schemes in addition to
      improving the accuracy in grading breast cancer nuclei.

PMID- 8885094
TI  - Improved determination of breast cancer size in mammography.
AB  - Breast cancer size determination in a preoperative stage is of great importance,
      as it is taking into account the classification of the tumour. In this paper a
      simple method of the improved determination of the actual tumour size is
      presented. The method is based on the calculation of correction factors taking
      into account the magnification of the tumour image during the mammographic
      examination. The method was applied for evaluation on forty cases of breast
      cancer. In all cases the final approximation of tumour maximum diameter with the
      presented method is almost equal to this obtained from the pathologists' reports.
      The possibility of wrong stage characterisation of a tumour, which is a problem
      arising from the measurement of the maximum diameter directly from the mammogram,
      is also minimised, especially in case that tumour size is between two stages.

PMID- 8885095
TI  - Analysis of temporal non-stationarities in EEG signals by means of parametric
      modelling.
AB  - A method for the analysis of variability of EEG signals is described. We examined
      simulated signals and real EEGs obtained from a normal subject and two epileptic
      patients. The first step of the method is based on autoregressive (AR) modelling
      of short EEG epochs. Prediction coefficients of the AR model were computed as a
      function of time from partially-overlapping moving windows of 2 s duration. The
      temporal behaviour of these coefficients was analysed to detect variability:
      quasi-stationary activity causes only smooth changes in the coefficients while
      variations in the amplitude and/or the frequency content of the signal are shown
      to produce sharp changes in the coefficients. A segmentation algorithm was
      developed to detect and quantify with a numerical value (Difference Measure, DM)
      the AR coefficients variations.

PMID- 8885096
TI  - A novel tele-medical environment appropriate for use in tele-advisory and tele
      surgery cases.
AB  - Tele-medical systems have been recently introduced in the field of networking as
      promising applications that can significantly improve the offering of medical
      treatment by providing services such as tele-advising, tele-surgery and remote
      monitoring in places where the presence of doctors or any medical specialists is
      difficult or time consuming. Some already existent networking models can be used
      for the establishment of a connection between the communicating sides. The
      offered network's security is also a significant factor. The present paper
      describes a software environment implementing a particular aspect of a tele
      medical system. The developed system includes features such as direct
      communication between doctors and medical assistants, medical information
      acquisition and storing and high band information transfer in real-time. TCP/IP
      point-to-point protocol has been used for the implementation of the non bandwidth
      critical connections. The application introduces novel features with the use of
      ATM connection for supporting the time-critical service of video transfer to and
      from the medical database.

PMID- 8885098
TI  - Rule induction and instance-based learning applied in medical diagnosis.
AB  - Machine learning methods have been applied in a variety of medical domains in
      order to improve medical decision making. Improved medical diagnosis and
      prognosis can be achieved through automatic analysis of patient data stored in
      medical records, i.e., by learning from past experience. Given patient records
      with corresponding diagnoses, machine learning methods are able to classify new
      cases either through constructing explicit rules that generalize the training
      cases (e.g., rule induction) or by storing (some of) the training cases for
      reference (instance-based learning). This paper presents the methodologies of
      rule induction and instance-based learning and their application to medical
      diagnosis, in particular, the problem of early diagnosis of rheumatic diseases.
      It also discusses the possibility to use existing expert knowledge to support the
      learning process and the utility of such knowledge.

PMID- 8885097
TI  - Improved monitoring of preterm infants by Fuzzy Logic.
AB  - Keeping the oxygenation status of newborn infants within physiologic limits is a
      crucial task in intensive care. For this purpose several vital parameters are
      supervised routinely by monitors, such as electrocardiograph, transcutaneous
      partial oxygen pressure monitor and pulse oximeter. Each monitor issues an alarm
      signal whenever an upper or lower limit of the parameter(s) measured is exceeded.
      However, in practice it turns out, that a considerable amount of false alarms is
      generated by artefacts, which are attributed mostly to movements of the infants.
      Eliminating these false alarms would be of benefit to the staff as well as the
      patients of the intensive care unit. Accordingly, an automated system based on
      Fuzzy Logic was developed, which is capable of distinguishing between critical
      situations and artefacts. The system is based on a Transputer IMS T425 in a PC,
      which collects the data from the monitors, plots it on a colour screen, saves it
      to hard disk and analyses it by Fuzzy Logic. Fuzzy algorithms were developed to
      generate more reliable alarms. All vital parameters of eight infants, who either
      moved often and/or frequently produced real alarm situations, were recorded.
      Synchronously the infants' movements and care procedures were video taped. The
      data and video were analysed off line with the help of an experienced
      neonatologist. His judgement was compared to the analysis of the Fuzzy Logic
      system. The results show that it is possible to improve the reliability of the
      monitored data with the aid of an evaluation strategy based on Fuzzy Logic and
      hence distinguish between real alarm situations and movement artefacts to the
      extent that an application in an intensive care unit under routine conditions
      becomes conceivable.

PMID- 8885099
TI  - An intelligent diagnostic system for the assessment of gestational age based on
      ultrasonic fetal head measurements.
AB  - The object of this study is the assessment of gestational age by using fetal
      biparietal diameter and head circumference based on automated image analysis and
      artificial neural networks. Standard ultrasonic measurements were made in 143
      normal fetuses between 14 and 40 weeks' gestation. Six hundred and thirteen fetal
      head images were transferred to a microcomputer environment by means of a frame
      grabber and spatial software. Biparietal diameter and head circumference
      measurements were made by automated image processing and analysis techniques. In
      the next stage, these two fetal parameters were used to determine the gestational
      age by using an unsupervised artificial neural network. Back propagation learning
      algorithm was trained by 552 fetal head images and the system was tested with the
      remaining 61 images. It has been demonstrated that 98% of gestational weeks were
      estimated correctly by our system.

PMID- 8885100
TI  - A new technique for monitoring central venous pressures and determining cardiac
      index in adults.

PMID- 8885101
TI  - Egyptian contributions to cardiovascular medicine.

PMID- 8885102
TI  - How serious is a proximal occlusion of a posterolateral sequential bypass?
AB  - The sequential coronary bypass, despite having several demonstrated benefits, has
      been criticized for being solely dependent upon 1 proximal anastomosis. The aim
      of this study was to evaluate the danger of a proximal occlusion of a
      posterolateral sequential bypass graft. Between 1 January 1984 and 31 December
      1994, 3,203 patients underwent primary coronary artery bypass grafting with at
      least 1 sequential vein bypass graft (780 patients received 1 sequential graft
      and 2,423 patients received 2). There were 5,626 sequential bypass grafts: 3,492
      posterolateral (62%) and 2,134 antero-latero-septal (38%) grafts. There were 73
      hospital deaths (2.3%). Follow-up was performed on 3,130 hospital survivors
      (5,504 grafts), for an average of 59 +/- 36 months (range, 1 to 11 years). During
      follow-up, a total of 250 symptomatic sequential graft occlusions occurred in 250
      patients (8.0%). Only 23 (0.7%) of the surviving 3,431 posterolateral sequential
      bypass grafts had symptomatic proximal occlusion, 35.9 +/- 5.9 months
      postoperatively, with all the distal anastomoses remaining patent. Twenty-two of
      the patients so affected presented with angina and 1 with myocardial infarction.
      There was no mortality. In 12 patients (52%), medical treatment was sufficient,
      while 11 patients (48%) underwent successful repeat coronary revascularization.
      The operation consisted of a simple vein graft from the aorta to the distally
      patent sequential graft in all patients. Four patients had additional coronary
      artery bypass grafting due to progression of the disease. The 10-year survival
      rate was 86.7%. Symptomatic occlusion of only the proximal segment of
      posterolateral sequential bypass grafts occurs rarely and has a low risk of
      myocardial infarction and mortality, provided that the terminal anastomosis is
      with a high-flow vessel.

PMID- 8885103
TI  - Endoaneurysmorrhaphy for left ventricular aneurysm. Follow-up in 69 patients.
AB  - We reviewed the cases of 69 consecutive patients who underwent physiologic
      reconstruction of the left ventricular cavity with an endoventricular patch
      (endoaneurysmorrhaphy) after aneurysmectomy. Eight patients had isolated
      endoaneurysmorrhaphy, 60 patients had concomitant coronary artery bypass
      grafting, and 1 patient had concomitant closure of an atrial septal defect. The
      primary indications for operation were angina pectoris (New York Heart
      Association functional class I or II) in 42 patients and dyspnea (functional
      class III or IV) in 27 patients. The preoperative left ventricular ejection
      fraction evaluated with ventriculography was 28.95% +/- 7.27% (mean +/- standard
      error of the mean). The global perioperative mortality rate was 2.8%. Total
      follow-up was 139.3 patient-years. The late mortality rate was 4.3% per patient
      year. A marked increase was found in the mean postoperative left ventricular
      ejection fraction of the patients: 41.91% +/- 11.83%. Survivors were interviewed
      in person: their functional status was class I or II in 58 patients and class III
      in 3 patients. We conclude that left ventricular endoaneurysmorrhaphy results in
      satisfactory functional improvement and can be performed with relatively low
      early and late mortality rates.

PMID- 8885104
TI  - Delayed primary closure of deep sternal wound infections.
AB  - Deep infections of the sternum and mediastinum, with prevalence of osteomyelitis
      and tissue necrosis, were documented in 38 of 8,056 patients (0.47%) who
      underwent open-heart surgery (1975 through 1994) in our service. The incidences
      of insulin-dependent diabetes, obesity, and emergency surgery in these patients
      were relatively high at 39%, 47%, and 18%, respectively. Treatment with
      antibiotics, debridement, open packing, and delayed closure was administered to
      33 patients (87%), with 100% healing. There were no deaths in this group. Flap
      reconstruction was indicated in 5 gravely ill patients (13%) in whom excessively
      large wound defects did not allow reapproximation. There were 2 deaths in this
      group, and 4 reoperations were necessary in the surviving patients because of
      sequelae arising from flap reconstruction. The overall mortality was 5.3% and the
      median period of hospitalization was 29 days. The length of stay decreased
      substantially over the period of this study (median = 21 days, year > or = 1987).
      Accordingly, we believe that treatment of deep sternal infections with delayed
      primary closure is safe and effective. Also, given the increased potential for
      complications and long-term sequelae, we believe that flap reconstruction should
      be used selectively and should be limited to patients with large defects,
      uncontrolled mediastinal bleeding, or both.

PMID- 8885105
TI  - Unruptured congenital aneurysm of the right sinus of Valsalva. Dissecting into
      the interventricular septum.
AB  - We report the case of a congenital aneurysm of the right sinus of Valsalva
      dissecting into the interventricular septum in a 21-year-old man. This condition
      was diagnosed by echocardiography and magnetic resonance imaging. In particular,
      transthoracic and transesophageal color-coded Doppler echocardiography showed
      that there was no communication between the aneurysm and the surrounding heart
      chambers. The findings were confirmed by angiography. Heart enlargement and other
      symptoms and signs of heart failure indicated surgical repair of the lesion.
      Early postoperative dehiscence of the sutured orifice was accurately diagnosed
      with Doppler echocardiography and angiography. Reintervention was successful in
      filling and sealing the septal cavity. This case confirms the reported
      difficulties in the surgical correction of aneurysms of sinus of Valsalva lying
      within the interventricular septum.

PMID- 8885106
TI  - Microvascular free myocutaneous flap for treatment of nonhealing ischemic ulcers
      of the lower extremity. A case report.
AB  - In diabetic patients, large foot ulcers that are unresponsive to conventional
      therapy have traditionally been treated by amputation. Arterial reconstruction
      alone has failed to stimulate healing of lesions with exposed bone and tendons in
      weight-bearing areas. We present a case in which complete healing of such an
      ulcer was achieved with a combination of percutaneous transluminal angioplasty
      and a microvascular free myocutaneous flap. Soon after discharge, the patient was
      able to walk well without assistance, and the muscle flap remained viable at 35
      months.

PMID- 8885107
TI  - Coronary steal through anomalous internal mammary artery graft. Treated by
      ligation without sternotomy.
AB  - A patient who had undergone adequate coronary revascularization with a left
      internal mammary artery graft to the left anterior descending coronary artery and
      with saphenous vein grafts to the right coronary artery and to the 1st and 2nd
      obtuse marginal branches presented with early-onset recurrent angina. A repeat
      angiogram showed an abnormally large branch arising from the very proximal
      segment of the left internal mammary artery and supplying the whole lateral chest
      wall via many intercostal tributaries. Relief of symptoms was achieved by
      ligation of this branch, and the patient remains symptom free more than 6 years
      after the procedure.

PMID- 8885108
TI  - Surgical management of left ventricular myxoma with embolization to the right
      coronary artery.
AB  - We report a rare case of left ventricular myxoma with embolization to the right
      coronary artery, presenting as an acute myocardial infarction. The tumor was
      excised from the left ventricle, and the tumor embolus was removed from the right
      coronary artery. Saphenous vein bypass grafting was also performed successfully.

PMID- 8885109
TI  - Regression of post-Fontan protein-losing enteropathy. After surgical correction
      of hemodynamic faults other than high right atrial pressure.
AB  - We describe a case of protein-losing enteropathy after a Fontan operation, in the
      absence of high right atrial pressure. Although partial regression of protein
      losing enteropathy was obtained with high doses of cortisone, complete resolution
      of the phenomenon was accomplished only after surgical closure of a left-to-right
      shunt through the pulmonary valve.

PMID- 8885110
TI  - Embolization of a complete prosthetic aortic valve to the abdominal aorta. Long
      term survival after surgery.
AB  - We describe a case of complete embolization of an aortic valve prosthesis to the
      abdominal aorta. To our knowledge, this patient is the 1st asymptomatic long-term
      survivor of this catastrophic event. In such cases, we recommend emergency
      surgery on the basis of echocardiographic results alone. Delay for more complete
      diagnostic evaluation is not warranted.

PMID- 8885111
TI  - Bedside diagnosis of cardiac tamponade.

PMID- 8885112
TI  - Pericardial tamponade.

PMID- 8885113
TI  - Subintimal hematoma of the aorta after deceleration injury.

PMID- 8885114
TI  - Serum concentrations of lamotrigine in epileptic patients: the influence of dose
      and comedication.
AB  - Lamotrigine (LTG) is a new antiepileptic drug (AED), chemically unrelated to the
      drugs in current use. Previous studies have shown that LTG has only a limited
      effect on other AEDs, but its own metabolism can be strongly induced or inhibited
      by the comedication. We investigated the influences of carbamazepine (CBZ),
      phenytoin (PHT), phenobarbital (PB), valproic acid (VPA), and combinations of
      these drugs on the serum concentration of LTG. A total of 588 blood samples from
      302 patients were analyzed. The mean duration of LTG therapy was 141 +/- 137 days
      (mean +/- SD). A patient was only considered twice in this study if his or her
      comedication had been changed. The LTG serum concentration in relation to LTG
      dose/body weight (level-to-dose ratio, LDR, microgram/ml/mg/kg) was calculated
      and compared for different drug combinations. The results showed that
      comedication had a highly significant (p < 0.001) influence on the LTG serum
      concentrations. The mean LDR for LTG was 0.32 (LTG + PHT) < 0.52 (LTG + PB)
      approximately equal to 0.57 (LTG + CBZ) < 0.98 (LTG mono) approximately equal to
      0.99 (LTG + VPA + PHT) < 1.67 (LTG + VPA + CBZ) approximately equal to 1.80 (LTG
      + VPA + PB) < 3.57 (LTG + VPA (<, p < 0.05; approximately equal to, p > 0.05,
      multiple comparisons). The mean LTG concentrations in patients on comedication
      with VPA were about two times higher than on patients on LTG monotherapy or on
      comedication without VPA (5.0 vs. 2.6 micrograms/ml), despite the LTG doses being
      half as high (3.0 vs. 5.9 mg/kg). The correlations of the serum concentrations
      and doses of CBZ, PB, PHT, and VPA with the LDR of LTG were only weak or not
      significant. Furthermore, the distribution of LTG serum concentrations and
      dosages was compared with the tentative therapeutic range for the LTG
      concentration (1-4 micrograms/ml), proposed by some investigators, and the
      recommendations for the LTG dosage. Remarkable discrepancies were observed. The
      comedication has an important influence on the LTG concentration and should be
      considered in LTG dosage.

PMID- 8885115
TI  - Validation of self-reported smoking by analysis of hair for nicotine and
      cotinine.
AB  - Evidence suggesting the use of self-reports as an index of systemic exposure to
      cigarette smoke in selected study populations is highly inaccurate. In order to
      assess the use of hair analysis as a biochemical marker of cigarette smoking, we
      compared measurements of nicotine and cotinine in the hair and plasma of 36
      volunteers whose reports of smoking were deemed to be reliable. A significant
      correlation was observed between the number of cigarettes smoked and hair
      measurements of nicotine (r = 0.48, p = 0.004) and cotinine (r = 0.57, p =
      0.0008). In addition, a good correlation was found between the reported number of
      cigarettes smoked and plasma nicotine, plasma cotinine, and carboxyhemoglobin
      levels. These results suggest that hair analysis is a reliable noninvasive method
      of determining human exposure to cigarette smoke and is comparable to blood
      analysis.

PMID- 8885116
TI  - Disposition of epirubicin after intraarterial administration in Lipiodol to
      patients with hepatocellular carcinoma.
AB  - Delivering emulsions of anthracycline drugs in Lipiodol, an iodinated poppy-seed
      oil, via the hepatic artery for the treatment of hepatocellular carcinoma (HCC)
      has become increasingly popular. However, investigations to determine the extent
      to which the Lipiodol sequesters the anthracycline in the liver have been
      limited. Concern has been expressed that such emulsions are not stable and that
      the anthracycline is, therefore, released rapidly into the circulation. We
      studied the pharmacokinetics of epirubicin (50 mg m-2) in five patients with
      nonresectable primary hepatocellular carcinoma after infusion of an
      epirubicin/Lipiodol emulsion via the hepatic artery. We used a reliable and
      specific high-performance liquid chromatography assay that allows quantitation of
      plasma concentrations of epirubicin, epirubicinol, epirubicin glucuronide, and
      epirubicin aglycone. Although a large interpatient variability in
      pharmacokinetics was observed, our results were similar to historical data after
      epirubicin intravenous therapy. Only the results from one patient provided
      evidence of significant retention of the drug in the liver. It would appear that
      more stable formulations of epirubicin/Lipiodol are required to increase the
      efficacy of this form of treatment. We suggest that pharmacokinetic studies
      should accompany clinical evaluation of emulsions of epirubicin/Lipiodol for the
      treatment of HCC.

PMID- 8885117
TI  - Blood concentrations and clinical effect of cyclosporin in psoriasis.
AB  - After approval by the Local Ethical Committee, 60 psoriatic patients, who
      participated in a previous pharmacokinetic study on cyclosporin A (CsA), gave
      their informed consent to continue to be studied during the maintenance treatment
      and at withdrawal. Peak concentration (Cmax), area under the concentration-time
      curve (AUC), bioavailability, elimination half-life, distribution volume, and
      body clearance were determined at monthly check-ups, along with blood pressure,
      psoriasis area, severity index (PASI), and creatinine serum levels. No
      modifications over time of treatment were observed on kinetic parameters. At the
      dose of 5 mg/kg in two daily administrations, a complete remission of the disease
      was observed after 1 month's treatment. At withdrawal, a worsening of PASI
      appeared when CsA daily dose reached 2 mg/kg b.w., the mean trough levels or AUC
      values being, respectively, 100 and 2,200 ng/ml.hr. There was a trend for
      patients with hypertension and nephrotoxicity at the end of the maintenance
      treatment to have higher trough, Cmax, and AUC values. Furthermore, blood
      pressure and serum creatinine tended to correlate better with AUC and Cmax, than
      with trough levels.

PMID- 8885118
TI  - Optimal gentamicin therapy in preterm neonates includes loading doses and early
      monitoring.
AB  - Recent studies have suggested the inadequacy of an initial gentamicin 2.5 mg/kg
      standard dose in neonates and the need for a loading dose. The purpose of this
      prospective, randomized study was to compare initial peak and initial trough
      serum gentamicin concentrations (SGC) in neonates after a standard dose (2.5
      mg/kg) or a loading dose (4 mg/kg) on the first day of life. A secondary
      objective of the study was to evaluate the use of two SGC drawn after the first
      dose in designing individualized dosage regimens, despite the many changes in
      gentamicin disposition that occur over the first week of life. Forty infants
      admitted to the NICU were randomized to receive either 2.5 or 4 mg/kg gentamicin.
      Individual gentamicin pharmacokinetic parameters were determined after the first
      dose. Initial peak SGC were > 5 mcg/ml in only 6% of neonates receiving 2.5
      mg/kg, versus 94% of neonates receiving 4 mg/kg. The initial trough after the
      first dose was < 2 mcg/ml in 100% of patients receiving 2.5 mg/kg and only 39% of
      patients receiving 4 mg/kg. Using two SGC after the first dose successfully
      predicted steady state peaks in 13/16 infants and steady state troughs in 14/16
      infants. Thus, standard treatment of 2.5 mg/kg gentamicin yields initial peak
      serum gentamicin concentrations < 5 mcg/ml in neonates while a 4 mg/kg gentamicin
      loading dose, combined with pharmacokinetic monitoring after the first dose,
      optimizes gentamicin therapy in neonates.

PMID- 8885119
TI  - Cyclosporine pharmacokinetics and risk of recurrent rejection in recipients of
      simultaneous pancreas/kidney transplants.
AB  - Recipients of a simultaneous pancreas/kidney transplant (SPK) appear to have a
      greater incidence of acute rejection than do recipients of a kidney-alone
      transplant. These patients are also susceptible to multiple rejection episodes.
      Because of this, optimal immunosuppression is imperative in these patients.
      Cyclosporine A (CsA)-based immunosuppression remains the mainstay of therapy, and
      therefore, optimization of this often unpredictable drug is necessary. We looked
      at 14 consecutive SPK recipients and assessed the utility of a single 1-month
      pharmacokinetic study in predicting the risk of acute rejection. Each
      pharmacokinetic study was analyzed by both monoclonal fluorescence polarization
      immunoassay (TDX) and high performance liquid chromatography (HPLC). Due to the
      small sample size and the high rate of primary rejection (12/14 patients), we
      chose a novel endpoint, that of recurrent rejection. Seven of the 14 patients
      studied developed recurrent rejection. The patients without recurrent rejection
      had significantly higher areas under the concentration curve (AUCs) than did
      patients with recurrent rejection: 4,663 +/- 1,460 vs. 2,454 +/- 1,717 ng-h/ml (p
      < 0.05) by HPLC and 6,669 +/- 2,556 vs. 3,661 +/- 1,956 ng-h/ml (p < 0.05) by
      TDX. We propose that a single 1-month AUC has potential utility in identifying a
      subset of SPK patients with poor CsA absorption at risk for recurrent rejection.

PMID- 8885120
TI  - Creatinine clearance as predictor of tobramycin elimination in adult patients
      with cystic fibrosis.
AB  - Assessment of renal function and relating this parameter to amino-glycoside
      clearance is important for an appropriate individualization of dosage regimens in
      patients with impaired renal function. However, it has been suggested that in
      cystic fibrosis (CF), creatinine clearance (CrCl) is not a good predictor of
      tobramycin clearance because of a lack of correlation. The aim of this study was
      to investigate the correlation between the tobramycin clearance and the measured
      CrCl. In addition, because most pharmacokinetic computer models use an a priori
      relationship between CrCl and tobramycin elimination rate constant [k(el)],
      regression analysis of k(el) on CrCl was performed. Eighteen CF patients (12 men,
      6 women, ages 21-55 years) were treated with intravenous tobramycin. Blood and
      urine samples were collected for tobramycin analysis and determination of the
      CrCl. For each patient, CrCl was also estimated using the formulas of Cockcroft
      and Gault (C/G), Jelliffe I (J I), and Jelliffe II (J II). Predictive performance
      of these formulas was evaluated using mean error and mean squared error as
      reflections of bias and precision. Tobramycin total body clearance as well as
      renal clearance correlated significantly with CrCl (r = 0.52; p = 0.02 and r =
      0.78; p = 0.02, respectively). Regression of the tobramycin k(el) versus CrCl
      gave the following equation: k(el) = 0.135 + 0.00134*CrCl/1.73 m2 (r = 0.64; p =
      0.004). The 95% confidence interval of intercept and slope of the regression line
      were 0.019-0.251 and 0.00049-0.00219, respectively. The formulas of C/G, J I, and
      J II all overpredicted CrCl. Bias was 19, 24, and 8 ml/min, and precision was 37,
      42, and 33 ml/min, respectively, for the C/G, J I, and J II formulas. In our CF
      population the J II formula gave the best estimation of the CrCl but calculated
      estimates deviated -25(-)+62% from measured values.

PMID- 8885121
TI  - Fluoxetine addition to methadone in addicts: pharmacokinetic aspects.
AB  - We report nine cases where fluoxetine (FX) (20 mg/day) was added to maintenance
      treatment with methadone (MTD) (dose range: 30-100 mg) in addicts with affective
      disorders. MTD plasma levels were measured before and after treatment with FX
      under steady-state conditions. Among the nine patients, two also received
      fluvoxamine (FLVX) at different times. Although it is possible that in some
      patients a moderate FX-MTD interaction occurs, resulting in increased plasma
      levels of MTD, this interaction is certainly less marked than that between FLVX
      and MTD and unlikely to have clinical consequences.

PMID- 8885122
TI  - Totally automated analysis by robotized PrepStation and liquid chromatography:
      direct-sample analysis of felbamate.
AB  - A totally automated analysis of felbamate was developed by using a robotized
      PrepStation for extraction, followed by automated liquid chromatographic (LC)
      analysis and data reduction. This is one of the newer direct-sample analysis
      approaches by LC. Felbamate was a previously approved antiepileptic agent used to
      treat partial seizures with and without generalization and to treat Lennox
      Gastaut syndrome in pediatric patients. However, due to the reported incidences
      of aplastic anemia, its clinical application was recently restricted to the
      treatment of the latter syndrome. The automated assay using Bench Supervisor,
      PrepStation, and LC, based on a previously developed manual method, used 200
      microliters of serum standards, quality control, or patients' plasma. These were
      mixed with 600 microliters of internal standard (IS) W509 dissolved in
      acetonitrile for protein precipitation. After axial centrifugation and standing,
      aliquots of the clear supernatant were transferred and washed with hexane.
      Aliquots of the supernatant were transferred and injected into a high-performance
      liquid chromatograph (HPLC). HPLC parameters included an mu Bondapak C-18 column,
      phosphate/acetonitrile (8:2) as mobile phase, and detection at 214 nm. Retention
      times were 2.9 and 4.2 min for felbamate and IS, respectively. Calibration was
      linear for concentrations from 10 to 200 mg/L with r > 0.994. Precision studies
      showed coefficients of variation ranging from 2.7% to 8.8%. Correlation with the
      manual method showed that r = 0.934, slope = 1.048, intercept = -2.642, and n =
      21. Phenobarbital coeluted with the IS. This study demonstrated the feasibility
      of using a robotized, automated method for monitoring felbamate, readily extended
      to monitoring other antiepileptic drugs with minimal modification.

PMID- 8885123
TI  - Bupropion plasma levels and CYP2D6 phenotype.
AB  - All available antidepressants with the exception of fluvoxamine and nefazodone
      either are metabolized by cytochrome P450 2D6 (CYP2D6) and/or inhibit this
      isozyme. To date, nothing in this regard has been published concerning bupropion.
      We report that plasma level/dose ratios for bupropion, and its metabolites
      erythrohydrobupropion and threohydrobupropion, were not associated with
      debrisoquine metabolic status in 12 patients, three of whom were poor 2D6
      metabolizers. The plasma level/dose ratios for the metabolite hydroxybupropion
      were, however, significantly higher in poor 2D6 metabolizers. In three patients,
      who received a second phenotyping test during treatment with bupropion,
      debrisoquine metabolic ratios were not increased. It is thus inferred that
      bupropion is neither metabolized by nor inhibits CYP2D6. The potential
      accumulation of hydroxybupropion after CYP2D6 inhibition may, however, contribute
      to toxicity and impair bupropion's therapeutic effectiveness.

PMID- 8885124
TI  - The influence of ethnic factors and gender on CYP1A2-mediated drug disposition: a
      comparative study in Caucasian and Chinese subjects using phenacetin as a marker
      substrate.
AB  - To assess potential ethnic and gender-related differences in the expression of
      cytochrome CYP1A2-mediated activity, the pharmacokinetics of phenacetin (a CYP1A2
      substrate) and its metabolite paracetamol were compared in 20 Caucasian and 20
      Chinese subjects after administration of a single oral 900 mg phenacetin dose.
      Peak plasma concentrations and apparent oral clearance values for phenacetin did
      not differ between the two groups (geometric means: 3.4 micrograms/ml and 1.56 ml
      h-1 kg-1, respectively, for Caucasians vs. 4.7 micrograms/ml and 1.25 ml h-1 kg
      1, respectively, for Chinese, after excluding one Caucasian with aberrantly low
      plasma phenacetin values). Pharmacokinetic parameters for metabolically derived
      paracetamol were also similar in the two groups. When subjects were divided into
      subgroups according to gender, phenacetin apparent oral clearance values were
      found to be lower in Chinese women compared with both Chinese men and Caucasian
      subjects of either sex. It is concluded that there are no major interethnic
      differences in the expression of CYP1A2-related activity between Caucasians and
      Chinese, although Chinese women as a subgroup may exhibit comparatively lower
      enzyme activity.

PMID- 8885125
TI  - High-performance liquid chromatography determination of pyrimethamine, dapsone,
      monoacetyldapsone, sulfadoxine, and N-acetyl-sulfadoxine after rapid solid-phase
      extraction.
AB  - A solid-phase extraction procedure and a corresponding high-performance liquid
      chromatographic technique based on methods previously published by Edstein et al.
      (Edstein M. Quantification of antimalarial drugs. I. Simultaneous measurement of
      sulphadoxine, N4acetylsulphadoxine and pyrimethamine in human plasma. J
      Chromatogr 1984;305:502-7; Edstein M. Quantification of antimalarial drugs. II.
      Simultaneous measurement of dapsone, monoacetyldapsone and pyrimethamine in human
      plasma. J Chromatogr 1984;307:426-31) were developed for simultaneous
      determination of either dapsone (DDS), monoacetyldapsone (MADDS), and
      pyrimethamine (PYR) or sulfadoxine (SDX), N-acetyl-sulfadoxine (NAS) and
      pyrimethamine in plasma. Solid-phase extraction was achieved using C-18
      extraction columns. An ionpair chromatography was performed on a C-18 analytical
      column (mu Bondapak C-18, 300 x 3.9 mm I.D.). Gradient elution with methanol,
      acetonitrile, PIC B6 reagent (1-hexanesulphonic acid), and water as mobile phase
      was applied. Ultraviolet detection was done at 210 nm for PYR, at 254 nm for SDX
      and NAS, and at 295 nm for DDS and MADDS. The extraction recoveries averaged
      92.1% for PYR, 87.6% for DDS, 87.5% for MADDS, 91.2% for SDX, and 92.4% for NAS.
      The limit of quantification using 1.0-ml plasma samples was 15 ng/ml for PYR,
      DDS, MADDS, NAS, and 25 ng/ml for SDX (precision < 15%).

PMID- 8885126
TI  - Column-switching high-performance liquid chromatography of ofloxacin in human
      saliva and correlation of ofloxacin level in saliva and serum.
AB  - A column-switching high-performance liquid chromatography (HPLC) assay was
      developed for the determination of ofloxacin in saliva. The saliva samples were
      directly introduced into a C8 HPLC column using a C18 precolumn. Ofloxacin and
      lomefloxacin as internal standards were detected spectrophotometrically at 300
      nm. Determination of ofloxacin was possible in the concentration range 50-3,000
      ng/ml, and the limit of detection was 20 ng/ ml. The recovery of ofloxacin added
      to saliva was 96.9-101.2% with a coefficient of variation of < 2.9%. These
      pharmacokinetic studies were made of healthy volunteers after treatment with
      ofloxacin. The maximum concentration of saliva and serum ofloxacin was 513.3
      2,053.0 ng/ml and 768.2-3,089.0 ng/ml for dose of 100 mg or 200 mg, respectively.
      The AUC0-6 was 1,736.8-6,519.9 ng/h/ml in saliva and 2,875.5-10,086.0 ng/h/ml in
      serum, respectively. The saliva versus serum concentration ratio was 0.4-0.7 for
      doses of 100 and 200 mg. A good correlation between saliva and serum level of
      ofloxacin was obtained by this HPLC method (r = 0.949).

PMID- 8885127
TI  - A high-performance liquid chromatographic assay for the determination of
      amphotericin B serum concentrations after the administration of AmBisome, a
      liposomal amphotericin B formulation.
AB  - A sensitive and selective high-performance liquid chromatographic (HPLC) method
      has been developed for the determination of amphotericin B in human serum. After
      methanol deproteinization, amphotericin B and 3-nitrophenol (internal standard)
      are separated by reversed-phase chromatography and detected by ultraviolet
      absorbance. The analysis of human serum after the standard addition of
      amphotericin B (0.05-200.0 micrograms/mL) demonstrated excellent precision and
      accuracy over a five-day period. The HPLC assay uses two standard curve ranges.
      The high sensitivity curve range for low AmBisome dosage (1.0 mg/kg) is 0.05-20.0
      micrograms/mL (curve 1), and the second curve range for the higher AmBisome dose
      regimens (2.5-5.0 mg/kg) is 0.5-200 micrograms/mL (curve 2). The intraday and
      interday coefficients of variations for standard curve 1 were 0.5-4.6% and 3.0
      11.5%, respectively. The limit of quantitation was 0.05 microgram/mL. The
      intraday and interday coefficients of variation for standard curve 2 were 2.0-3.6
      and 6.9-10.1, respectively. No interfering peak at the retention time for
      Amphotericin B and the internal standard were present in blank serums or serum
      samples spiked with fifteen potential co-administrated drugs with Amphotericin B
      treatment. The method was used to quantitate serum concentrations of amphotericin
      B in patients after the administration of AmBisome, a liposomal formulation of
      amphotericin B.

PMID- 8885128
TI  - Comparison of high-performance liquid chromatography and polyclonal fluorescence
      polarization immunoassay for the monitoring of midazolam in the plasma of
      intensive care unit patients.
AB  - Midazolam (M) is used as an induction agent for anesthesia. The main metabolite
      is alpha-hydroxymidazolam (OM), which is pharmacologically active. Use of M for
      sedation is a recent application, rapidly gaining favor. Monitoring of the level
      of sedation is fundamental in that an excessive and prolonged effect is
      associated with the risk of complications. Thus, it was felt both necessary and
      useful to measure circulating M levels. We compared a high-performance liquid
      chromatography (HPLC) assay with fluorescence polarization immunoassay (FPIA) for
      the measurement of M in the serum of 138 sedated patients in the intensive care
      unit (i.e., 179 samples). Response of the OM was also assessed. The degree of
      crossover of the metabolite was between 76.8 and 32.7%. The equation of the
      regression line for sigma HPLC (i.e., the sum M + OM) versus FPIA was TDx =
      1.1585 sigma HPLC + 143.42 (R = 0.966). The 95% confidence interval for the slope
      was 1.1551, 1.1619. The regression slope differed significantly from 1 (p <
      0.001) and shows that FPIA measurements overestimated concentrations obtained by
      HPLC on the order of 19%. The discrepancy between the two techniques was all the
      more notable when concentrations were > 1,000 ng/ml. The relative selectivity of
      Abbott industrial reagent in terms of benzodiazepines leads to the identification
      of what might be called a midazolam-like (M-like) activity covering both M and
      OM. The development of a global FPIA method for measurement of this M-like
      activity in sedated patients provides a satisfactory solution to the question
      raised.

PMID- 8885129
TI  - A simple and rapid method for the determination of D-sorbitol in plasma using the
      Cobas Mira S.
AB  - The standard enzymatic assay for quantification of D-sorbitol in plasma was
      adapted to the automatic analyzer Cobas Mira S. In the assay, NAD (reagent) in
      the presence of sorbitoldehydrogenase (SDH; start reagent) converts D-sorbitol to
      fructose with formation of NADH, which was detected automatically as the
      difference between the first and last readings at 340 nm. The sample blank values
      for each specimen were subtracted to exclude both endogenous D-sorbitol and
      sugars, which also react as substrates for SDH. The method is simple, rapid (40
      samples/h), precise down to endogenous concentrations (coefficient of variation <
      5%; limit of determination: 0.38 mg/L) and linear up to 100 mg/L. Samples with
      higher D-sorbitol concentrations were estimated after dilution. The method was
      used to measure disposition curves of sorbitol in volunteers after a single
      intravenous dose of 0.8 g sorbitol.

PMID- 8885130
TI  - Possible interaction between cyclosporine and glibenclamide in posttransplant
      diabetic patients.
AB  - The possible occurrence of a kinetic interaction between cyclosporine A and
      glibenclamide was assessed by reviewing data of six posttransplant diabetic
      patients who received the two drugs concurrently. Coadministration of the two
      drugs resulted in a 57% increase in the steady-state plasma cyclosporine levels
      despite normal hepatic and renal functions in the patients. This elevation in
      cyclosporine level is possibly due to an interaction between the two drugs
      resulting from an inhibition of CYP3A4-mediated metabolism of cyclosporine by
      glibenclamide. This observation calls for a closer monitoring of cyclosporine
      plasma levels during concomitant administration of these two drugs in this group
      of patients.

PMID- 8885131
TI  - Tumour dormancy and cell signalling--III: Role of hypercrosslinking of IgM and
      CD40 on the induction of cell cycle arrest and apoptosis in B lymphoma cells.
AB  - Polyclonal anti-IgM antibodies were more effective than monoclonal antibodies in
      inducing dormancy in SCID mice bearing a murine B lymphoma (BCL1). Under
      saturating conditions, both polyclonal and monoclonal anti-Ig antibodies induced
      cell cycle arrest (CCA) in both BCL1 cells and human B lymphoma cells (Daudi) but
      polyclonal antibodies were far more effective at inducing apoptosis. A mixture of
      several monoclonal antibodies specific for noncrossreactive epitopes on C mu
      mimicked the effects of a polyclonal anti-mu. Hypercrosslinking mIgM by a
      polyclonal antibody against the primary monoclonal anti-mu markedly increased
      apoptosis and CCA. Hence, the extent of crosslinking of IgM and the resultant
      singnalling may be a major factor in inducing and maintaining dormancy and in
      determining whether lymphoma cells respond by apoptosis or CCA. In contrast to
      mIgM, another B cell receptor, CD40, which induces CCA when crosslinked did not
      induce apoptosis after hypercrosslinking. The results are consistent with the
      hypothesis that aspects of the CCA and apoptotic pathways are independent. When
      anti-CD40 was added with anti-mu to Daudi cells, the proportion of cells
      undergoing apoptosis was increased.

PMID- 8885132
TI  - Antitumour activity of a melanoma-specific immunotoxin, ME20-LysPE40.
AB  - An immunotoxin conjugate has been prepared by linking an internalizing antibody
      with melanoma selectivity, ME20, with a binding-defective form of Pseudomonas
      exotoxin A, LysPE40. ME20-LysPE40 binds to a 105,000 Da cell-surface antigen
      present on melanoma cells (ME20-M) within twofold of unmodified ME20 and was
      cytotoxic to two human melanoma cell lines, H3606 and MALME-3M, with EC50 values
      of 100 and 200 pM, respectively. Immunotoxin treatment, initiated 1 day following
      subcutaneous implantation of H3606 melanoma cells into mice, prevented outgrowth
      of tumour xenografts in > 50% of the mice. In contrast, only a modest inhibition
      in tumour growth was observed if the immunotoxin was administered 5 days after
      implantation of in vivo passaged H3606 tumour fragments in mice. This study shows
      that the internalizing monoclonal antibody ME20 IgG can be used for targeting a
      toxin toward melanoma cells displaying the ME20-M antigen.

PMID- 8885133
TI  - Development of a hormone neutralizing vaccine, using GnRH-glycys-PPD, for use in
      the treatment of oestrogen-dependent disorders.
AB  - The aim of this study was to develop an effective and nontoxic vaccine, suitable
      for use in humans, which was capable of effectively controlling oestrogen levels.
      Female Sprague-Dawley rats were immunized with a conjugated analogue of
      gonadotrophin releasing hormone, GnRH-glycys-PPD. This resulted in high levels of
      neutralizing antibody which disrupted GnRH function and consequently caused a
      reduction in serum oestrogen. The effect of oestrogen deprivation correlated well
      with ovarian failure and gonadal atrophy. An examination was made of various
      adjuvants in conjunction with the analogue to determine the suitability of the
      combinations in the formulation of an effective human vaccine. This investigation
      included a novel adjuvant, non-ionic surfactant vesicles (NISV); the results
      showed that NISV are completely nontoxic and in terms of potentiating and
      sustaining an immune response, compare favourably with Freund's adjuvant and
      alum. In addition the long term effects of immunization were investigated and the
      data showed that immunoneutralization of GnRH effectively suppresses fertility on
      a long-term basis.

PMID- 8885134
TI  - Immunomodulation by LFA3TIP, an LFA-3/IgG1 fusion protein: cell line dependent
      glycosylation effects on pharmacokinetics and pharmacodynamic markers.
AB  - LFA3TIP, a fusion protein comprised of the first extracellular domain of LFA-3
      fused to the hinge, CH2, and CH3 domains of human IgG1 inhibits responses of
      human and non-human primate T cells in vitro. In seeking to optimize the
      expression efficiency to prepare large quantities of LFA3TIP for primate studies,
      the protein was produced in both the CHO (Chinese hamster ovary) and murine NS-0
      myeloma cell lines. Although LFA3TIP derived from these cell lines performs
      identically in vitro in CD2 receptor binding and T cell assays, examination of a
      pharmacodynamic marker-the reduction in CD2+ lymphocyte numbers-following the
      administration of equal doses of NS-0 or CHO derived LFA3TIP to baboons,
      suggested that the effect of the NS-0 derived material was less sustained.
      Pharmacokinetic analysis of the materials in baboons and mice shows that LFA3TIP
      produced by NS-0 cells is rapidly cleared from circulation relative to the
      product derived from CHO cells. The disparate clearance profiles correlate with
      distinct glycosylation patterns, with LFA3TIP derived from NS-0 cells being less
      extensively sialylated than that from CHO cells due in part to alpha-galactosyl
      capping of selected lactosamine moieties in the N-linked glycans of NS-0 derived
      LFA3TIP. Moreover, enzymatic desialylation of CHO derived LFA3TIP results in a
      glycoprotein with an evanescent serum profile when administered to mice and
      baboons. These results correlate the extent of N-acetylneuraminic acid capping
      with the clearance rates of LFA3TIP derived from the two distinct cell lines, and
      underscore the importance of evaluating glycosylation dependent PK parameters
      when choosing production cell lines for recombinant immunotherapeutics.

PMID- 8885135
TI  - Cytotoxic lymphocytes: redirecting the cell-mediated immune response for the
      therapy of cancer.
AB  - Cytotoxic CD8+ T cells and NK cells are involved in the elimination of some
      viruses, graft rejection, antitumour responses, immunoregulation and some
      autoimmune diseases. The key role of these cells in each of these immune
      responses and the therapeutic potential they offer when effectively harnessed,
      has warranted continued interest in their function. A molecular approach has
      dominated the recent study of cytotoxic lymphocyte function, allowing the
      characterization of recognition structures on cytotoxic lymphocytes, the
      definition of two distinct mechanisms of cytotoxicity and the elucidation of
      their relevance in vivo. Currently, biological and genetic experimental
      approaches which exploit the targeted cytolytic activity of lymphocytes are being
      developed for cancer therapy. A greater understanding of the biology of cytotoxic
      lymphocytes when adoptively transferred, the development of re-engineered mAbs
      with tailored properties and the characterization of newly defined endogenous
      tumour cell antigens, has brought us to the brink of using these cells to greater
      therapeutic advantage. This review briefly examines ongoing efforts to
      characterize the mechanism of action of cytotoxic lymphocytes and describes the
      progression of approaches designed to enhance the anti-tumour activity of these
      cells.

PMID- 8885136
TI  - Platelet accumulation induced by bacterial endotoxin in rats.
AB  - We studied the effects of i.v. administration of endotoxin (Escherichia coli,
      Serotype 0127:B8) on the kinetics of 111In-labelled platelets within the
      pulmonary, abdominal and splenic vascular beds of the rat, and on the
      radioactivity present in dissected samples of splenic and hepatic tissues. Bolus
      i.v. injection of endotoxin to anaesthetised rats caused a dose-dependent,
      transient accumulation of 111In-labelled platelets in the pulmonary vasculature.
      Increased radioactivity, suggestive of platelet sequestration, was detected in
      tissue samples from both the spleen and the liver at 4.5 h compared to the
      radioactivity detected in those organs in vehicle treated rats. The modulation of
      endotoxin-induced platelet accumulation within the lungs, spleen and liver by
      pharmacological agents was investigated. The pulmonary, hepatic and splenic
      platelet accumulation induced by endotoxin was unaffected by pre-treatment of the
      animals with indomethacin, Hirulog or L-NAME. Pre-treatment with dexamethasone
      significantly reduced the platelet accumulation within the liver and spleen, but
      not the lungs.

PMID- 8885137
TI  - Differential effects of Lys- and mini-plasminogen on clot lysis induced by
      recombinant urokinase and recombinant pro-urokinase in a canine thrombosis model.
AB  - These studies were conducted to examine the lytic efficacy of recombinant
      urokinase (r-UK) and pro-urokinase (r-proUK) in the presence and absence of
      truncated forms of plasminogen. Due to differences in their structures, these
      modified proteins are more readily activated to plasmin than the circulating form
      of plasminogen. Use of such modified substrates for plasminogen activators may
      improve the clinical outcome in patients treated for a variety of thrombotic
      diseases. Lys-plasminogen (46 units) or mini-plasminogen (in units of equivalent
      chromogenic activity), in conjunction with r-UK (7,500 units), were administered
      in the absence of heparin to dogs (9-11 kg) in which a radiolabelled thrombus was
      formed in a femoral artery. Fibrinolysis was measured as a loss of radioactivity
      from the clot. After intra-arterial administration of the agents, clot lysis was
      48 +/- 8%, 50 +/- 9% and 75 +/- 2% in the presence of r-UK + vehicle, r-UK + lys
      plasminogen, and r-UK + mini-plasminogen, respectively. When these treatment
      groups were examined in the presence of heparin (500 units + 350 units/hour) in a
      second study, r-UK (2,000 units) produced clot lysis of 54 +/- 3%; addition of
      lys- or mini-plasminogen to the regimen resulted in lysis of 62 +/- 9% and 46 +/-
      10%, respectively. A third phase of the study examined r-proUK (1,000 units) with
      heparin; in this case, lysis was 51 +/- 9% in the presence of vehicle, but 55 +/-
      17% and 10 +/- 5% when lys- and mini-plasminogen were administered, respectively.
      Flow restoration, measured in the femoral artery in each experiment, generally
      paralleled the lytic profile. The results indicate that supplementation with mini
      plasminogen is only useful when added to a lytic regimen in the absence of
      heparin, and that lys-plasminogen, in conjunction with either of the lytic
      agents, does not improve clot lysis in this canine model.

PMID- 8885139
TI  - The effect of cholesterol oxidation products on human platelet aggregation.
AB  - The cholesterol oxidation products (oxysterols) cholest-3,5-diene-7-one,
      cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol (cholesterol 5 alpha-epoxide),
      cholestan-5 beta, 6 beta-epoxy-3 beta-ol (cholesterol 5 beta-epoxide), cholest-5
      ene-3 beta-ol-7-one (7-ketocholesterol), cholest-5-ene-3 beta, 7 alpha-diol (7
      alpha-hydroxycholesterol), cholestan-3 beta, 5 alpha, 6 beta-triol (cholestane
      triol), and cholest-5-ene-3 beta, 26-diol (27-hydroxycholesterol) potentiated
      platelet aggregation and increased thromboxane A2 formation in platelets
      challenged with thrombin, ADP or collagen. These effects were observed at
      oxysterol concentrations in the range 5-100 microM. Cholesterol 5 beta-epoxide
      and 7-ketocholesterol increased the mobilization of 3H-arachidonic acid from
      prelabelled platelet phospholipids in response to thrombin and collagen.

PMID- 8885138
TI  - Analysis of the expression of glycosylphosphatidylinositol anchored proteins on
      platelets from patients with paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal disorder is
      manifested by failure of hematopoietic cells to express phosphatidylinositol
      glycan-anchored proteins (PIG-AP). Since the PIG-A mutation is present at the
      stem cell level, all cell lines may be affected. Although the pathogenesis of
      hemolytic anemia in PNH is related to the absence of CD55 and CD59 molecules on
      the membrane of red cells, the mechanism responsible for the increased incidence
      of thrombotic events in PNH is not clear. In this study we measured two
      glycosylphosphatidylinositol (GPI)-linked molecules on platelets (CD55 and CD59)
      and two GPI-linked proteins on neutrophils (CD14 and CD16), comparing their
      expression on normal and PNH patients. Using two-color flow cytometric analysis
      with antibodies directed against CD42b and CD41a, we found that CD55 and CD59
      were constitutively expressed by normal fresh platelets, but that the expression
      levels decreased during the five day storage of platelets. A substantial
      population of platelets lacking the GPI-linked proteins were detected in most
      cases. We demonstrated varying degrees of deficiency in the expression of GPI
      anchored molecules with neutrophils, monocytes and platelets with the highest
      proportion of deficient cells found within monocytic lineage. Similar numbers of
      platelets with the PNH phenotype and normal platelets expressed activation
      markers before and after exposure to platelet agonists. Flow cytometry is more
      sensitive than Ham's test in monitoring expression of PNH in platelets.
      Differences in the numbers of circulating GPI-deficient platelets and myeloid
      cells suggest that either the survival of platelets and mature myeloid cells
      differs or megakaryocytopoeisis is abnormal within the GPI-deficient clone.

PMID- 8885140
TI  - Comparative anticoagulant effects of various thrombin inhibitors, as determined
      in the ecarin clotting time method.

PMID- 8885141
TI  - Negatively charged leucocyte filter significantly enhances kallikrein and
      thrombin-like activities of platelet concentrates.

PMID- 8885142
TI  - High prevalence of the FVR506Q mutation causing APC resistance in a region of
      southern Sweden with a high incidence of venous thrombosis.

PMID- 8885143
TI  - Menopause and risk of cardiovascular disease.

PMID- 8885144
TI  - Active site for heparin cofactor II in low molecular mass dermatan sulfate.
      Contribution to the antithrombotic activity of fractions with high affinity for
      heparin cofactor II.
AB  - Dermatan sulfate (DS) is currently under clinical investigation as new
      antithrombotic agent. Unlike heparin, DS does not act through Antithrombin III
      (ATIII) but primarily through thrombin on Heparin Cofactor II (HCII). HCII is
      activated by the oversulfated sequence (IdoA2SO3-GalNAc4SO3)4 or by both the
      sequences (IdoA2SO3-GalNAc4SO3)n and (IdoA-GalNAc-4,6SO3)n, [n > or = 2]. A Low
      Molecular Mass Dermatan Sulfate (LMM-DS), endowed with a bioavailability three
      four times higher than DS, by subcutaneous route, was obtained by chemical
      depolymerization of DS. The LMM-DS was fractionated by anion exchange and size
      exclusion chromatography. Fractions with high and low charge densities, high and
      low molecular masses, and high (2.66) and low (0.07) potencies on HCII were
      isolated. A relationship between the in vitro HCII-mediated inhibition of
      thrombin and the chain length of DS fractions containing oversulfated sequences
      was found [by a multiple regression test]. The in vivo activity increased until
      it reached a plateau. The important influence on the HCII activity of natural
      IdoA-GalNAc-4,6SO3 disaccharide was confirmed by investigation on oversulfated DS
      obtained by a limited and selective chemical 6-O-sulfation in GalNAc4SO3 units of
      DS.

PMID- 8885145
TI  - Interaction between Yersinia pestis YopM protein and human alpha-thrombin.
AB  - YopM, a 41.5 kDa virulence protein of Yersinia pestis is believed to have an anti
      inflammatory role in bubonic plague. It has been shown previously that YopM binds
      human alpha-thrombin but not prothrombin and inhibits thrombin-induced platelet
      aggregation in vitro. In the present studies we carried out crosslinking
      reactions between purified YopM and alpha-thrombin or its blocked form FPR-alpha
      thrombin in the presence of various competitors to identify where on thrombin
      YopM binds. We found that thrombin cleaves YopM at the C-terminus, indicating
      that this part of YopM must interact with thrombin's catalytic site. Hirudin, a
      65 amino acid natural thrombin inhibitor, prevents both the YopM degradation and
      the formation of a ca. 75 kDa crosslinking complex between YopM and alpha
      thrombin. A similar effect is observed when hirugen, a short peptide
      corresponding to hirudin's C-terminus (amino acids 58-64), is used as a synthetic
      thrombin inhibitor. A 15 bp long specific oligonucleotide known to block alpha
      thrombin successfully competes with YopM for the thrombin-binding site, whereas a
      control, scrambled sequence aptamer does not. As these competitors block a
      fibrinogen binding site (also called anion binding exosite I), our crosslinking
      data indicate that YopM binds not only to the active site of alpha-thrombin but
      also to the abeI.

PMID- 8885146
TI  - Monitoring thrombin generation with prothrombin fragment 1.2 assay during
      cardiopulmonary bypass surgery.
AB  - Despite high plasma levels of heparin during cardiopulmonary bypass surgery,
      activation of the coagulation system has been reported. We hypothesize that the
      coagulation system activity most appropriately could be assessed by molecular
      markers of thrombin generation. The aim of the present study was to describe the
      changes in thrombin generation during CPB, using prothrombin fragment F1 + 2
      (F1.2) as an indicator and evaluate different blood sampling regimens for
      interpretation of the F1.2 measurements. Twenty patients, operated under
      extracorporeal circulation with coronary artery bypass grafting (CABG), comprised
      the study material. The heparin levels were maintained above 2.5 IU/ml throughout
      the bypass procedure and the functional AT-III level was kept above 0.5 U/ml.
      Despite of this anticipated inactivation of the coagulation system, the
      concentrations of F1.2 and FpA increased throughout CPB, particularly after
      release of the aortic crossclamp. F1.2 and FpA correlated significantly (R =
      0.69). No statistically significant correlation was found between F1.2 formation
      rate and age, bodyweight, baseline ACT, ACT after 200 IU heparin/kg, average
      heparin concentration during CPB or average AT-III level during CPB. CONCLUSIONS:
      Thrombin formation seems to be a continuous process during CPB despite adequate
      heparinization. The pattern of thrombin generation can be assessed most
      appropriately in terms of F1.2 generation rate. Extraordinary high levels of F1.2
      were seen after release of the aortic crossclamp, indicating that the periods
      before and after aortic crossclamping should be evaluated separately.

PMID- 8885147
TI  - Effect of multimerization of human and recombinant von Willebrand factor on
      platelet aggregation, binding to collagen and binding of coagulation factor VIII.
AB  - The smallest circulating von Willebrand factor (vWF) molecule is a dimer composed
      of two identical subunits containing binding sites for heparin, collagen,
      platelet glycoproteins and coagulation factor VIII (FVIII). Interdimeric
      disulfide linking leads to multimers composed of up to 40 dimers. vWF serves as a
      carrier of FVIII and is required for normal interactions of platelets with the
      subendothelium of the injured vessel wall. Von Willebrand factor was purified
      from human plasma cryoprecipitate and fermentation supernatant of recombinant CHO
      cells by anion exchange chromatography. Heparin affinity chromatography was used
      to isolate vWF polymers of different degree of multimerization. Analysis of
      collagen binding and platelet aggregation revealed that these activities increase
      with increasing degree of multimerization of vWF. Binding of FVIII to vWF was
      studied by real-time biospecific interaction analysis and surface plasmon
      technology. The binding data showed that the binding of FVIII is independent of
      vWF multimerization. Using recombinant FVIII and recombinant vWF, real-time
      biospecific interaction analysis resulted in a potential stoichiometry of 2 to
      2.5 vWF-subunits per bound FVIII molecule. The kinetic analysis of the vWF-FVIII
      interaction resulted in a binding rate constant of about 3 x 10(6) M-1 s-1 and an
      equilibrium dissociation constant of about 0.4 x 10(-9) M.

PMID- 8885148
TI  - Human intraplatelet 5-hydroxytryptamine is correlated with mean platelet survival
      time.

PMID- 8885149
TI  - Prion disease and blood transfusion.

PMID- 8885150
TI  - A matter for debate: the risk of bovine spongiform encephalopathy to humans posed
      by blood transfusion in the UK.
AB  - If human infection with bovine spongiform encephalopathy (BSE) were to occur,
      donated peripheral blood from humans that might have become infected from eating
      adequate quantities of food containing BSE should, until evidence is available to
      the contrary, be assumed to contain the human form of the disease. The chance of
      disease transfer to a blood recipient in 1995, which might in turn cause clinical
      disease with an incubation period of 20 years, is calculated. Transfusion is
      calculated to be a potential cause of a maximum of only 0.2% of clinical cases of
      Creutzfeldt-Jakob disease (CJD) in the UK population if the BSE epidemic were to
      spread to humans. Prospective epidemiological techniques would be unlikely to
      demonstrate any such minor contribution that blood transfusion might make to CJD
      incidence.

PMID- 8885151
TI  - Autologous blood transfusion in radical hysterectomy.
AB  - The application of a hospital-based presurgical autologous blood deposit
      programme to support of radical hysterectomy is described over 4 years (1991-95),
      during which 48 patients participated in the autologous blood programme, and 63
      did not to do so. All but one of the autologous donors received autologous blood
      but only two received allogeneic blood. Forty-three of the autologous nondonors
      received no transfusion and 20 received allogeneic blood. These differences are
      highly significant. For the 48 autologous donors, 91% of the blood requested was
      collected, and of that 91% was used, for a "wastage' rate of 9%. The mean blood
      use was significantly greater in the autologous donors. Blood loss was not
      significantly different between the two groups. The data confirm the validity of
      the autologous blood order schedule of 2 units for radical hysterectomy.

PMID- 8885152
TI  - A pharmacokinetic/pharmacodynamic model for the action of anti-D immunoglobulin
      in effecting circulatory clearance of Rh D+ red cells.
AB  - A dynamic model of the action of anti-D immunoglobulin in effecting clearance of
      Rh D-positive red cells from the circulation of D-negative subjects is presented.
      The pharmacokinetics of the redistribution of anti-D between injection site,
      intravascular and extravascular spaces following either intramuscular or
      intravenous administration is included, also the reaction of anti-D with D
      positive red cells in the intravascular space and subsequent circulatory
      clearance of antibody-coated cells. Numerical computer modelling methods have
      been used to obtain solutions of the model, using kinetic rate constants which
      have been derived from previously published experimental data. Selected solutions
      are presented, chosen for their relevance to (i) clinical situations in which
      anti-D is used to prevent Rh D immunization of D-negative subjects and (ii)
      determination of some of the properties of anti-D antibodies which are important
      for effecting circulatory clearance of D-positive red cells.

PMID- 8885153
TI  - Role of Fc gamma RIIa (CD32) in IgG anti-RhD-mediated red cell phagocytosis in
      vitro.
AB  - To test the role of Fc gamma RIIa in IgG anti-RhD-mediated phagocytosis three
      IgG1 and two IgG3 human monoclonal anti-D antibodies were tested for ability to
      mediate binding/phagocytosis of cDE/cde and -D-/-D- red cells by Fc gamma RIIa
      R131 and Fc gamma RIIa-H131 cDNA-transfected 3T6 fibroblasts. Both IgG3
      monoclonal antibodies brought about -D-/-D- cell interaction with IIa-transfected
      fibroblasts, while only one of them, Og3, mediated binding of cDE/cde targets.
      Although Fc gamma RIIa expression was three times greater on IIa-R131 than on IIa
      H131 fibroblasts, the latter bound significantly more Og3-coated cDE/cde- and
      IgG3 anti-D-sensitized -D-/-D- cells, respectively, than the former effectors and
      showed some phagocytosis of the -D-/-D- targets. IgG1 anti-D antibodies were
      inactive in mediating red cell interaction with the fibroblasts. Moreover,
      monoclonal anti-Fc gamma RII IV.3 partially inhibited the phagocytosis by adult
      or fetal monocytes of Og3-sensitized cDE/cde cells. Fc gamma RIIa-H/H131
      monocytes exhibited higher phagocytic indices towards these targets than
      monocytes of other IIa allotypes. The results indicate that Fc gamma RIIa can
      participate in the phagocytosis of red cells coated with IgG3 anti-D; in this
      case the allotype of the receptor will modify the extent of red cell destruction.

PMID- 8885154
TI  - Evidence for an expression of blood group A antigen on platelet glycoproteins IV
      and V.
AB  - Blood group ABO antigens are known to be carried by several platelet
      glycoproteins (GP), e.g. GPIb, GPIIa, GPIIb, GPIIa and PECAM. Beside these
      proteins, we recently observed that blood group A antigen was also expressed on
      some other uncharacterized platelet proteins (70-90 kDa) having electrophoretic
      mobilities closely resembling those of GPIV and GPV. These findings prompted us
      further to characterize these latter ABO-expressing platelet proteins. By antigen
      capture ELISA, wherein the monoclonal antibodies (mAbs) CLB-IVC7 and CLB-SWI6
      were used to hold the corresponding antigens GPIV and GPV, human anti-A
      specifically bound to these proteins derived from A1-platelets; neither GPIV nor
      GPV derived from A2-, B- or O-platelets bound anti-A. In a Western blot assay
      using immunoprecipitated GPIV and GPV as antigens, mAb anti-A immunostained GPIV
      and GPV precipitated from A1, but not from A2 and O platelets. These results
      conclusively demonstrate that blood group A antigen is expressed on platelet GPIV
      and GPV.

PMID- 8885155
TI  - Use of prostaglandin E1 during preparation of platelet concentrates.
AB  - A paired study in 10 autologous volunteer donors was undertaken to investigate
      the efficacy of adding prostaglandin E1 (PGE1) in vitro during routine platelet
      concentrate (PC) production. After 5 days storage, PCs prepared with PGE1 were
      compared with control PCs. In vivo platelet recovery, survival and
      biodistribution were determined following autologous infusion of indium-111
      labelled platelets into volunteers, together with the in vitro evaluation of
      platelet function and biochemistry. PGE1 facilitated easier and faster platelet
      resuspension following centrifugation. After storage there were few significant
      in vitro differences between PCs prepared with PGE1 and control PCs. The
      artifactual leucocyte concentration was significantly lower in the presence of
      PGE1, suggesting less platelet aggregates had been formed during storage and beta
      thromboglobulin release was significantly reduced by PGE1, 14.0 +/- 6.0
      micrograms per 10(9) platelets compared with 22.3 +/- 9.8 micrograms per 10(9)
      platelets in control PCs, (P < 0.01), indicating PGE1 reduced both platelet
      aggregation and activation probably at the initial preparation stage, known to
      produce the greatest trauma. Initial in vivo platelet recovery for PCs prepared
      with PGE1 was similar to that of control PCs, 41.1 +/- 12.5% vs. 44.4 +/- 8.0%,
      respectively, and there were no differences in organ distribution at 24 h.
      However, in vivo multiple hit survival was reduced in the presence of PGE1, 5.8
      +/- 1.6 days compared with 6.9 +/- 1.4 days in control PCs (P < 0.05). Despite
      the ability of PGE1 to facilitate platelet resuspension and inhibit platelet
      aggregation and activation during preparation of the PCs, the reduced in vivo
      survival time may preclude the use of PGE1 during routine PC preparation.

PMID- 8885156
TI  - Comparison of the Lewis phenotypes among the different population groups of
      Taiwan.
AB  - In Caucasians, three red cell Lewis phenotypes are observed, namely Le (a+b-), Le
      (a-b+) and Le (a-b-). For Chinese living in Taiwan the Le (a+b-) phenotype is
      replaced by the Le (a+b+) phenotype so that the three red cell Lewis phenotypes
      observed in Chinese are Le (a+b+), Le (a-b+) and Le (a-b-). In addition, Chinese
      individuals with Le (a-b-) red cells can be subdivided into two groups, namely
      those who secrete both ABH and Lewis substances in saliva and those who secrete
      only ABH substances in saliva. However, four red cell Lewis phenotypes Le (a+b-),
      Le (a+b+), Le (a-b+) and Le (a-b-) are observed among some of the indigenous
      groups living in Taiwan. Red cell Le (a+b-) individuals among these indigenous
      groups can also be subdivided into at least two groups, namely those with Le(a)
      and Le(b) in saliva (plus varying amounts of ABH substances) and those with just
      Le(a) in saliva. The former are most likely a weak form of the red cell Le (a+b+)
      phenotype while the latter appear to be similar to the Caucasian red cell Le (a+b
      ) phenotype. There was also one red cell Le (a+b-) individual whose saliva had a
      small amount of A substance as well as Lea substance and therefore appeared to be
      intermediate between the above two forms of the Le (a+b-) phenotype.

PMID- 8885157
TI  - Guidelines on gamma irradiation of blood components for the prevention of
      transfusion-associated graft-versus-host disease. BCSH Blood Transfusion Task
      Force.

PMID- 8885158
TI  - Guidelines for pre-transfusion compatibility procedures in blood transfusion
      laboratories. BCSH Blood Transfusion Task Force.

PMID- 8885159
TI  - The IgA-deficient blood donor: something in the air?
AB  - In May 1994, the Blood Transfusion Centre, Sheffield, introduced a new screening
      test for Immunoglobulin A (IgA) deficiency. The test is performed in parallel
      with routine donor ABO grouping and Rh typing on two Olympus PK 7200
      autoanalysers. A panel of IgA-deficient donors is required to provide blood
      products for IgA-deficient patients in whom the presence of anti-IgA antibodies
      may cause serious anaphylactic transfusion reactions (Welborn & Hersch, 1991).
      Detection rates during high summer became noticeably inconsistent and since a
      relationship between IgA deficiency and hypersensitivity states is recognized
      (Amman & Hong, 1971), a comparison between the detection rate and pollen levels
      during June and July 1994 was undertaken; the results of this study are presented
      here.

PMID- 8885160
TI  - In pursuit of enigmatic platelet antibodies--anti-HPA-2b and anti-HPA-3a.

PMID- 8885161
TI  - An HIV antibody positive plasma donor detected at the early stage of HIV
      infection in China.

PMID- 8885162
TI  - Autologous blood: really suitable for homologous use?

PMID- 8885163
TI  - HPV E6: ensuring all's well at the end.

PMID- 8885164
TI  - Emptying Pandora's box: cytosolic export and MHC degradation.

PMID- 8885165
TI  - Climate change and the threat from infection.

PMID- 8885166
TI  - Biosafety concerns and Coxiella burnetii.

PMID- 8885167
TI  - A hypothesis for the induction of sarcoidosis.

PMID- 8885168
TI  - Cell entry and the pathogenesis of Bartonella infections.
AB  - Erythrocyte parasitism, or hemotrophy, is not a common strategy for bacteria.
      However, Bartonella species are elegantly adapted to parasitize a variety of cell
      types including red blood cells. Bartonella bacilliformis, a useful model
      organism for the genus, has been used to study virulence determinants involved in
      colonization, attachment and invasion of host cells.

PMID- 8885169
TI  - The contributions of retroelements to plant genome organization, function and
      evolution.
AB  - Plant genomes are rich in mobile DNAs of several retroelement classes. The great
      abundance, broad dispersion, and hypervariability of plant retroelements indicate
      that they make a major contribution to host genome organization, function and
      evolution.

PMID- 8885170
TI  - Antibodies against Candida: potential therapeutics?
AB  - For many years, there has been controversy over the role of antibodies in
      immunity to Candida, but recently specific antibodies to mannoproteins and hsp90
      have been shown to be protective against murine candidiasis. Combined with
      technical advances in antibody engineering, this raises the possibility of
      harnessing such antibodies into a new range of therapeutics.

PMID- 8885171
TI  - Postbinding functions of CD4 in HIV infection.
AB  - Several studies have suggested that the CD4 molecule, in addition to serving as
      the HIV receptor, may also be involved in postbinding events of HIV infection.
      The CD4 molecule has been shown to assume an altered conformation on the T-cell
      surface following HIV binding, which may be involved in these postbinding events.

PMID- 8885172
TI  - Biogenesis of the peribacteroid membrane in root nodules.
AB  - An infected root nodule cell may contain several thousand rhizobial symbionts,
      each enclosed in a membrane envelope, the peribacteroid membrane (PBM). The PBM
      is derived from the host plasma membrane, but shares properties with the vacuolar
      membrane and contains several nodule-specific proteins (nodulins) that perform
      unique functions for symbiosis.

PMID- 8885173
TI  - Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca
      fascicularis): an animal model of human non-insulin-dependent diabetes mellitus.
AB  - To further characterize spontaneous diabetes mellitus in cynomolgus macaques
      (Macaca fascicularis) as a model for human non-insulin-dependent diabetes
      mellitus (NIDDM), we evaluated the morphologic characteristics of the endocrine
      pancreas of 4 diabetic and 12 age-matched nondiabetic cynomolgus macaques. In
      addition, the cDNA-predicted amino acid sequence for islet amyloid polypeptide
      (IAPP) of this species was determined. Islet amyloid deposits exhibiting typical
      congophilia and green birefringence were found in 4/4 diabetic animals and in
      8/12 nondiabetics. Islet amyloid deposits were significantly more extensive in
      the diabetic macaques (P = 0.001), in which they occupied a mean of 60% of the
      islet area. In contrast, in the nondiabetic group the maximum islet area occupied
      by amyloid was 24% (group mean = 6.8%), with four animals having no detectable
      islet amyloid. Amyloid deposits consistently showed immunoreactivity for IAPP but
      not for insulin. Comparisons between group means for diabetic versus nondiabetic
      macaques showed significantly greater islet area (P = 0.01, 85,390 versus 36,540
      microns 2) and significantly greater islet area fraction (P = 0.02, 0.065 versus
      0.032) for the diabetic group. The cDNA-predicted amino acid sequence for
      cynomolgus IAPP was identical to that previously reported for pig-tail macaques
      (M. nemestrina) and had 92%, 86%, and 84% amino acid sequence identity with
      human, domestic cat, and murine IAPPs, respectively. These findings support the
      use of cynomolgus macaques as an animal model of human NIDDM.

PMID- 8885174
TI  - Associations between lymphocytic thyroiditis, hypothyroidism, and thyroid
      neoplasia in beagles.
AB  - The thyroids were evaluated in 276 control Beagles that were allowed to live out
      their full life span (mean = 12 years) in a closed breeding colony. Lymphocytic
      thyroiditis was found in 26.3% of the dogs. This lesion was characterized by
      lymphoplasmacytic inflammation accompanied by follicular destruction. The
      thyroiditis was progressive, resulting in severe atrophy of follicular tissue,
      and 44 dogs (15.9%) were diagnosed as hypothyroid at the time of death. In
      accordance with the experimental protocol, hypothyroid dogs were not given
      thyroxine replacement therapy. There was a high degree of heritability for the
      hypothyroidism. Hypothyroid dogs had an increased risk for thyroid follicular
      epithelial neoplasia and, in particular, for follicular adenocarcinomas. Twenty
      four of the 44 hypothyroid dogs (54.5%) had one or more follicular thyroid
      neoplasms, whereas only 53 of the 232 (22.8%) clinically euthyroid dogs had
      similar tumors. Multiple thyroid tumors were present in 14 of the 44 (31.8%)
      hypothyroid dogs but in only 12 of the 232 (5.2%) euthyroid dogs. One or more
      follicular adenocarcinomas were present in 15 of the 44 (34.1%) hypothyroid dogs
      but in only 16 of the 232 (6.9%) euthyroid dogs. There was no difference in
      prevalence of hypothyroidism or tumors between the sexes. The strong association
      between progressive lymphocytic thyroiditis, hypothyroidism, and thyroid
      follicular neoplasia in these Beagles probably relates to promotion of residual
      follicular epithelium by chronic excess thyrotropin stimulation.

PMID- 8885175
TI  - Status spongiosis, optic neuropathy, and retinal degeneration in Helichrysum
      argyrosphaerum poisoning in sheep and a goat.
AB  - Lesions of natural Helichrysum argyrosphaerum poisoning were studied in eight
      sheep and one goat. Light microscopic examination revealed widespread,
      bilaterally symmetrical status spongiosis of the white matter of the brain
      consistently present in the subependymal area adjacent to the lateral ventricles,
      cerebellar peduncles, and brain stem in all animals. In three animals, the
      ultrastructural finding of intramyelinic vacuolation due to splitting of the
      myelin lamellae at the intraperiod lines indicated myelin edema. There was also
      mild distension of perivascular and extracellular spaces in the severely affected
      areas. Significant changes were absent in neurons, glial cells, axons, or blood
      vessel walls. Myelin edema associated with degeneration and loss of axons and
      myelin and astrocytic gliosis was present in the intraorbital and intracranial
      portions of the optic nerves. In the intracanalicular portions of the nerves in
      three animals that were studied, more chronic lesions consisting of fibrosis and
      atrophy of the nerve suggested that the optic neuropathy follows compression of
      the nerve in the optic canal as a result of myelin edema. The toxic principle of
      the plant also caused a degenerative retinopathy in five animals. The essential
      histopathologic change was degeneration and loss of the photoreceptor outer
      segments predominantly in the nontapetal retina. These retinal lesions were
      associated with hyperplasia and hypertrophy and with migration of the pigmented
      epithelium, focal retinal separation, and depletion and loss of the nuclear
      layers.

PMID- 8885176
TI  - Type I Glanzmann's thrombasthenia in a Great Pyrenees dog.
AB  - An 8-month-old female Great Pyrenees dog with chronic epistaxis and a history of
      gingival bleeding during shedding of deciduous teeth was evaluated for platelet
      function. Platelet morphology was normal at both the light and electron
      microscopic level. Platelet number and mean platelet volume were also normal.
      Platelet aggregation responses to adenosine diphosphate, collagen, platelet
      activating factor, and thrombin were markedly reduced, although shape change
      responses were normal. Clot retraction was markedly impaired. Monoclonal antibody
      (MoAb) Y2/51, a murine anti-human platelet beta 3 antibody that cross-reacts with
      canine platelet beta 3, and MoAb 5G11, a murine anti-dog platelet alpha IIb beta
      3 antibody, bound minimally to affected dog platelets, as demonstrated by flow
      cytometry. Binding of MoAb Y2/51 was not detectable by immunoblot. MoAb CAP1, a
      murine anti-dog fibrinogen receptor-induced binding site antibody, failed to bind
      to affected dog platelets, as demonstrated by flow cytometry. A reduction in
      glycoproteins alpha IIb and beta 3 was demonstrated by two-dimensional protein
      electrophoresis. This is the first reported case of type I Glanzmann's
      thrombasthenia in the dog that closely resembles the clinical syndrome and the
      platelet morphology described in type I Glanzmann's thrombasthenia of human
      beings.

PMID- 8885177
TI  - Immunohistochemical and morphological characterization of spontaneously occurring
      pheochromocytomas in the aging mouse.
AB  - Pheochromocytomas in mice are rare tumors, and their expression of functional
      markers has not previously been assessed. In this study, 29 spontaneously
      occurring mouse pheochromocytomas were characterized morphologically and
      immunohistochemically to determine whether there are functional correlates to
      previously described morphological features and to provide a database for
      comparison with tumors that arise in genetically engineered animals. The tumors
      were derived from 28 mice 828-1,489 days old, of three genotypes. Considerable
      cytological and architectural polymorphism was observed both within and between
      tumors. Most of the tumor cells were comparable in size to normal chromaffin
      cells or were larger. Small basophilic cells, which are the predominant cell type
      in rat pheochromocytomas, were usually in the minority. All of the tumors and
      most of the cells within individual tumors expressed immunoreactive tyrosine
      hydroxylase (TH). The tumors were variably positive for phenylethanolamine-N
      methyltransferase (PNMT) and chromogranin A (CGA). There did not appear to be a
      global association of specific cytological features with expression of TH, PNMT,
      or CGA, although cells of similar appearance often shared similar
      immunoreactivities within individual tumors. Small basophilic cells could be
      either PNMT-positive or PNMT-negative. The frequency, morphology, and
      immunophenotype of mouse pheochromocytomas suggest that the mouse may be more
      appropriate than the rat as a model for human adrenal medullary pathology. In
      addition, the expression of immunoreactive PNMT by mouse pheochromocytomas
      suggests that these tumors are a potential source of epinephrine-producing cell
      lines, for which adequate models currently do not exist.

PMID- 8885178
TI  - Histopathologic evaluation of feline inflammatory liver disease.
AB  - To better define the histopathologic features of feline inflammatory liver
      disease, we studied feline liver biopsies evaluated at the University of
      Minnesota Veterinary Teaching Hospital over a 10-year period. Of 175 liver
      sections examined, 45 had portal inflammatory infiltrates. Of these, 60% had
      infiltrates consisting of lymphocytes and plasma cells, 24% had infiltrates
      consisting of neutrophils, and 16% had mixed infiltrates consisting of
      neutrophils, lymphocytes, and plasma cells. Lymphocytic-plasmacytic portal
      infiltrates were characterized by various degrees of bile duct proliferation and
      fibrosis without evidence of bile duct infiltration or periportal necrosis.
      Sections with portal neutrophilic infiltrates were characterized by bile duct
      infiltration, bile duct epithelial degeneration, periportal necrosis, and
      infiltration of neutrophils into adjacent lobules. We propose that hepatitis
      characterized by portal lymphocyte and plasma cell infiltration be termed
      lymphocytic portal hepatitis and that hepatitis characterized by cholangitis and
      portal neutrophilic infiltrates with or without lymphocytes and plasma cells be
      termed cholangiohepatitis.

PMID- 8885179
TI  - Number of nucleoli and nucleolar organizer regions per nucleus and nucleolus-
      prognostic value in canine mammary tumors.
AB  - Twenty-eight canine mammary tumors were evaluated for histopathologic
      classification as recommended by the World Health Organization and silver-binding
      nucleolar organizer region (AgNOR) and nucleolus counts. Samples of surgically
      excised tumors and tumors taken at necropsy were fixed in neutral formalin,
      embedded in paraffin, and cut into 1-3-microns-thick sections. Two sections were
      taken from each tumor: one was stained with hematoxylin and the other was treated
      with the silver staining technique for the demonstration of AgNORs. After
      histopathologic classification, the number of nucleoli and the number of
      AgNORs/nucleus and AgNORs/nucleolus were determined. Statistical analysis
      (Student's t-test) showed a significant difference in the mean number of nucleoli
      (P < 0.005), mean number of AgNORs/nucleolus (P < 0.001), and mean number of
      AgNORs/nucleus (P < 0.005) between benign and malignant canine mammary tumors.
      There was no significant differences between metastatic and nonmetastatic
      malignant tumors.

PMID- 8885180
TI  - Immunohistochemical detection of P-glycoprotein in formalin-fixed and paraffin
      embedded normal and neoplastic canine tissues.
AB  - Expression of P-glycoprotein, a phylogenetically conserved integral plasma
      membrane protein, is implicated as one of the most important factors contributing
      to tumor cell multidrug resistance. Formalin-fixed, paraffin-embedded normal and
      neoplastic canine tissues were studied using an avidin-biotin complex technique
      employing three murine monoclonal antibodies (C494, C219, JSB-1) to different
      epitopes of the P-glycoprotein molecule. Evaluation of immunostaining of normal
      canine tissues revealed positive labeling detected by each antibody in the liver,
      proximal renal tubular epithelium, adrenal cortex, colonic epithelium, and
      capillary endothelial cells of the brain. A total of 166 tumors of epithelial or
      mesenchymal origin were evaluated for P-glycoprotein immunoreactivity. Hepatomas
      (4/4), colorectal adenomas (7/7), colorectal carcinomas (4/4), adrenal cortical
      adenomas (3/3), hemangiopericytomas (15/15), apocrine gland adenocarcinomas (4/5,
      80%), and transitional cell carcinomas (2/2) consistently labeled with at least
      one of the antibodies. Histiocytomas (0/10), cutaneous plasma cell tumors (0/10),
      fibromas (0/3), fibrosarcomas (0/4), and leiomyomas (0/4) were uniformly negative
      with all antibodies. Malignant lymphomas (6/22, 27.3%), malignant melanomas
      (4/13, 30.8%), leiomyosarcomas (3/6, 50%), mammary gland carcinomas (12/19,
      63.2%), mammary gland adenomas (3/9, 33.3%), squamous cell carcinomas (8/10,
      80%), basal cell tumors (5/7, 71.4%), apocrine gland adenomas (1/2, 50%),
      cholangiocarcinomas (2/3, 66.7%), and thyroid gland carcinomas (2/4, 50%) gave
      variable results. The antibodies C494, JSB-1, and C219 labeled 66/166 (39.8%),
      53/166 (31.9%), and 38/166 (22.9%) of all tumors studied, respectively. A total
      of 26/166 (15.7%), 22/166 (13.3%), and 37/166 (22.6%) of tumors were labeled by
      all three, just two, or one antibody alone, respectively. The antibody C494 was
      the only antibody labeling 28/166 (16.9%) of the cases. JSB-1 alone labeled 9/166
      (5.4%) of the tumors. C219 failed to label any tumors not also labeled by either
      C494 or JSB-1. Labeling by C494 was more intense and specific than labeling by
      the other two antibodies. Results indicate that P-glycoprotein can be detected in
      routinely processed canine tissues. The detection of P-glycoprotein within canine
      liver, kidney, adrenal gland, and colon and within tumors arising from these
      tissues is consistent with that reported in the literature for human tissues.
      Variable labeling results of other tumors such as malignant lymphoma and mammary
      gland carcinomas also is consistent with reports of human studies. Detection of
      multidrug resistance markers such as P-glycoprotein in canine tissues may provide
      additional information upon which to base a prognosis or to design treatment
      regimens for canine tumors.

PMID- 8885181
TI  - Light microscopic and ultrastructural changes in the ceca of chicks inoculated
      with human and canine Serpulina pilosicoli.
AB  - Light microscopic and ultrastructural changes were observed in chicks challenged
      with North American Serpulina pilosicoli, a weakly beta-hemolytic intestinal
      spirochete (WBHIS) associated with human and canine intestinal spirochetosis.
      Chicks in control groups received trypticase soy broth or canine Serpulina
      innocens. The birds were necropsied at weekly intervals, and the ceca were
      processed for bacteriologic and pathologic examinations. No WBHIS were isolated
      from the ceca of chicks in the control groups, but WBHIS with genotypes similar
      to the parent isolates were isolated from the ceca of chicks inoculated with
      human and canine S. pilosicoli. Gross examination revealed no significant changes
      in the ceca of chicks at any time post-inoculation. Light microscopic examination
      revealed no spirochetal attachment in the ceca of chicks in control groups. In
      contrast, focal to diffuse thickening of the brush border of the surface
      epithelium along with dilation of the crypt lumina and mild focal lamina propria
      heterophil infiltration were present in the ceca of chicks inoculated with human
      and canine S. pilosicoli. Scanning electron microscopic examination revealed
      focal to confluent spirochetal attachment mainly in the furrow region at the
      periphery of the crypt units. Transmission electron microscopic examination
      revealed spirochetes attached to the brush border of the cecal epithelium,
      causing effacement of the microvilli and disruption of the terminal web
      microfilaments. The cecal epithelium of chicks inoculated with the canine S.
      pilosicoli also had caplike elevations of the apical membrane at the point of
      attachment of the spirochetes together with large numbers of vesicles in the
      cytoplasm immediately beneath the terminal web and evidence of spirochetal
      invasion beyond the mucosal barrier. The changes observed suggested that the
      mechanism of attachment of human and canine S. pilosicoli to the cecal epithelium
      of chicks was analogous to but different from that described previously for other
      attaching and effacing gastroenteric bacterical pathogens of human beings and
      animals.

PMID- 8885182
TI  - Chronological immunohistochemical detection and localization of porcine
      reproductive and respiratory syndrome virus in gnotobiotic pigs.
AB  - An immunogold-silver immunohistochemical technique was used to determine the
      chronological distribution and localization of porcine reproductive and
      respiratory syndrome virus (PRRSV) in experimentally infected gnotobiotic pigs.
      Thirty-two pigs were randomly allocated to infected (n = 24) or control (n = 8)
      groups. Pigs in infected groups were inoculated at 3 days of age by nasal
      instillation of PRRSV isolate ATCC VR-2332 (total dose = 10(2.64) TCID50), and
      control pigs were exposed in the same manner to uninfected cell culture
      supernatant. Three infected and one control pigs were euthanatized at 12 hours
      and at 1, 2, 3, 5, 7, 14, and 21 days postexposure (DPE). Bronchiolar epithelial
      cells, arteriolar endothelial cells, monocytes, and interstitial, alveolar, and
      intravascular macrophages stained for PRRSV antigen at 12 hours postexposure.
      Staining for PRRSV antigen in endothelial cells, monocytes, and alveolar,
      interstitial, and intravascular macrophages was most intense and widespread in
      lung sections from 14 and 21 DPE. In the heart, macrophages in the interstitial
      and subendocardial spaces and endothelial cells in a few arterioles stained for
      PRRSV antigen at 14 and 21 DPE. Tonsillar macrophages and mucosal epithelium
      stained for PRRSV antigen at 12 hours postexposure and sporadically with less
      intensity in subsequent sampling periods. In the nasal turbinate, PRRSV antigen
      was identified in macrophages within the mucosal epithelium at 12 hours
      postexposure and again at 14 and 21 DPE. There was focal staining for PRRSV
      antigen in the choroid plexus in one pig at 14 DPE. Based on the results of this
      experiment, the pathogenesis of PRRSV infection in gnotobiotic pigs can be
      described as initial virus entry through nasal epithelial, tonsillar, and
      pulmonary macrophages, with viremia occurring by 12 hours postexposure followed
      by the development of pneumonia, myocarditis, encephalitis, rhinitis, vasculitis,
      and lymphoid necrosis. Although PRRSV can infect macrophages in heart, tonsil,
      turbinate, and choroid plexus, pulmonary macrophages are predominantly and
      consistently infected and are the predominantly cells for virus replication in
      gnotobiotic pigs.

PMID- 8885183
TI  - High incidence and histogenesis of seminal vesicle adenocarcinoma and lower
      incidence of prostate carcinomas in the Lobund-Wistar prostate cancer rat model
      using N-nitrosomethylurea and testosterone.
AB  - The origin of chemically induced male accessory sex gland tumors was studied in
      Lobund-Wistar rats. Rats were treated at the age of 3 months with a single
      intravenous injection of 30 mg N-nitrosomethylurea (NMU)/kg body weight and given
      subcutaneous silastic implants filled with 40 mg testosterone propionate.
      Previous reports described a high incidence of prostate carcinomas in these rats
      with this treatment protocol. Additional animal groups included untreated
      controls, rats that received only an injection of 30 mg NMU/kg, and rats that
      were subjected to ablation of the seminal vesicle lobes prior to the treatment
      with NMU and testosterone. Three to 14 rats per group were sacrificed 4 to 10
      months after NMU treatment and all remaining rats after 12 months. Twenty-four
      additional rats died or became moribund during the study. All rats were
      necropsied and the dorsolateral and ventral prostate and seminal vesicles with
      coagulating gland (anterior prostate) were examined histologically according to a
      standardized protocol. Lesions detected included atypical hyperplasia in all
      glands (resembling prostate intraepithelial neoplasia of human beings), adenomas
      in seminal vesicles only, and early carcinomas and adenocarcinomas in seminal
      vesicles and coagulating gland. Early carcinomas of the seminal vesicle,
      microscopically small and with invasion of the lamina propria and/or tunica
      muscularis, were detected as rapidly as 4 months after treatment. The vast
      majority (> 95%) of the grossly visible nodules/masses originated from the
      seminal vesicles. Testosterone treatment enhanced occurrence and increased the
      incidence of all lesions, particularly of seminal vesicle adenocarcinomas, from
      30% (7/23) to 64% (21/33). Coagulating gland tumors were found in 21% (7/33) of
      the rats. Ablation of the seminal vesicle lobes reduced the incidence of seminal
      vesicle adenocarcinomas to 11% (3/29), and these tumors arose from tissues
      remaining within the parenchyma of the seminal vesicle/prostate complex after
      ablation. Thus, NMU-induced and testosterone-promoted male sex gland tumors of
      the Lobund-Wistar rat arise almost exclusively in the seminal vesicles and
      coagulating gland (anterior prostate), are highly invasive in seminal vesicles
      before attaining a grossly visible size, and progress rapidly within 4 months,
      spreading to adjacent tissues and other organs.

PMID- 8885184
TI  - On opening "black boxes" and looking inside.

PMID- 8885185
TI  - Evaluation of the effectiveness of guidelines, audit and feedback: improving the
      use of intravenous thrombolysis in patients with suspected acute myocardial
      infarction.
AB  - OBJECTIVE: To determine the effectiveness of medical audit as a means of
      improving the use of intravenous thrombolytics in patients with suspected acute
      myocardial infarction. DESIGN: Time-series analyses of observations in four study
      hospitals conducting repeated audits and feedback compared to a control hospital.
      SETTING: Five district general hospitals in North West Thames Region between
      April 1991 and July 1992. SUBJECTS: 2593 patients admitted as emergencies with a
      suspected acute myocardial infarction. MAIN OUTCOME MEASURES: Proportion of
      eligible cases receiving intravenous thrombolytic therapy observed in each audit
      and proportion of patients in whom this therapy was used appropriately. RESULTS:
      In the baseline audits, the proportions of eligible cases receiving thrombolytic
      therapy in the four study hospitals were 94%, 60%, 58% and 57%, and 53% in the
      control hospital. After three further audits in each study hospital over the
      subsequent year, the observed proportions had changed to 88% (to 6%), 92% (+32%),
      95% (+37%), and 7796 (+20%). Meanwhile the proportion in the control hospital
      rose to 68% (+15%). The trend over time was significant in the second and third
      hospitals but not in the other two study hospitals or the control hospital.
      Reclassification of those cases in which the reliability of the diagnosis was
      poor altered the extent but not the direction of observed trends. Generally, the
      appropriateness of use of thrombolytic therapy increased with increasing
      treatment rates. There was a suggestion, however, that continued auditing in the
      presence of high treatment rates may have led to a reduction in appropriateness.
      CONCLUSIONS: medical audit can be an effective means of improving the use of
      intravenous thrombolytics. It is possible that over auditing may result in
      greater inappropriate use.

PMID- 8885186
TI  - Establishing thresholds for adverse patient outcomes.
AB  - OBJECTIVE: To establish thresholds for adverse patient outcomes in the absence of
      knowledge of patient illness severity indices. OUTCOMES: Pulmonary embolism,
      unplanned return to operating rooms, unplanned readmissions, clean and
      contaminated wound infections, and hospital-acquired bacteraemia. DESIGN:
      Analysis of results of surveys of hospitals in Australia by the Australian
      Council on Healthcare Standards following the introduction of clinical
      performance measures into the Accreditation process. SETTING: Acute care
      hospitals in Australia undergoing Accreditation surveys in 1993 and 1994.
      METHODS: Stratification of hospitals into small (1-99 beds), medium (100-199
      beds), and large (> or = 200 beds), calculation of mean rates for the above
      outcomes in each group, and establishment of thresholds based on two standard
      errors from the mean. RESULTS: The mean rate of occurrence of incidents was
      higher for larger hospitals. Thresholds were generally lower for smaller and
      higher for larger hospitals. CONCLUSIONS: Bed-size is a useful index for
      "flagging" peer group variation. The methodological issues in establishing
      thresholds and their implications in monitoring the quality of care in hospitals
      are discussed.

PMID- 8885187
TI  - Quality assessment: is the focus on providers or on patients?
AB  - Most studies of ambulatory care quality are based on chart reviews of episodes of
      care in single settings, rather than on care received by a patient over time and
      across settings. The purpose of this study was to compare ambulatory care quality
      scores based on information from the usual source of care to scores based on
      information from all providers seen during a year. The quality of well child care
      for 55 two-year-olds and asthma care for 70 children and adults continuously
      enrolled in the Maryland Medicaid program throughout 1988 was assessed. Combining
      data from multiple providers changed quality scores in both directions. For well
      child care, quality scores generally improved because of an increased opportunity
      to perform desirable actions, such as lead screening. However, quality scores for
      asthma care generally decreased because undesirable clinician actions, such as
      the failure to document follow-up plans, increased as more problems were
      uncovered. Thus, the findings of quality assessments differ according to whether
      the focus is on care delivered by individual providers or on care received by
      patients. The direction of the difference will depend upon whether the indicators
      of quality represent omission of recommended care or commission of improper care.

PMID- 8885188
TI  - Patients' and carers' satisfaction with hospital-in-the-home care.
AB  - AIM: Hospital-in-the-Home Units (HHUs) offer acute care, such as the
      administration of intravenous antibiotic therapy, to appropriate and consenting
      patients in their homes. This study sought to determine the satisfaction of a
      group of patients and carers to a hospital in the home program in Victoria,
      Australia. METHOD: A descriptive survey based on a telephone administered
      structured interview was conducted. PATIENTS admitted to the HHU from December
      1994 until the end of June 1995, and their nominated carers, were approached for
      their participation 2-3 weeks after their discharge. RESULTS:  PATIENTS: Surveys
      were completed for 67 of a total 79 patients (84.8%). A preference for the
      convenience and comfort of home was the commonest reason cited for agreeing to
      enter the HHU (45 or 67.2%). Almost all respondents (66) would use the service
      again if the opportunity arose. Benefits associated with the home environment
      were the commonest perceived advantages of HHU care (42, 62.3%). Carers: Sixty
      five carers from a possible 79 were interviewed. Most carers were women (spouses
      or mothers), and gave their occupation as home carer or retired. Sixty-two carers
      were confident in their role in the HHU. A similar number stated that they would
      act as carers again, and 61 would recommend the role to others. CONCLUSION: This
      study demonstrates that patient and carer preference will act as an incentive in
      the development and acceptance of HHU care.

PMID- 8885189
TI  - Aspects of patient satisfaction with communication in surgical care: confirming
      qualitative feedback through quantitative methods.
AB  - This paper reviews the results of a two-phase study of patient satisfaction with
      surgical services. Phase one adopted a qualitative approach using interviews and
      observation of surgeons and patients. Phase two was based on a questionnaire
      survey using questions generated by the qualitative study. Selected data reported
      here focus on the principal areas of concern for surgical patients and the
      importance of a patient's medical condition in accounts of satisfaction with
      care. The results reveal the importance of interview data as a means to explain
      the meanings behind questionnaire responses. However, where personal accounts are
      not sustained statistically, it may be necessary to reconsider the assumption
      that such methodologies may simply be "triangulated" to elicit an identical
      patient perspective and agenda. This is important in view of the fact that health
      research is increasingly reliant on standardized measures of quality-of-life,
      symptom-scoring and patient satisfaction, all of which use questionnaires whose
      claim to validity is their equivalence to the results of prior interviewing.

PMID- 8885190
TI  - Patient attitudes to major surgery in rural Kenya.
AB  - In this Kenyan study of patient perceptions of major surgery and involvement in
      decisions to operate, the attitudes of 89 female and 23 male patients who had
      undergone major surgery at a district hospital were studied. Semi-structured
      interviews were conducted in the wards by a social worker who had no employment
      or other relationship with the hospital. In 48 cases the decision about the
      operation was taken jointly by patient and doctor, while in 49 cases the decision
      was reportedly taken by the doctor alone. In 81 cases (64 female and 17 male) a
      relative or friend accompanied the patient to hospital. Only 21 patients reported
      being told details about the operation before the event. One quarter of the
      patients (housewives and school children) admitted feeling afraid or nervous
      prior to the operation while two-thirds reported having felt either confident or
      resigned about it. Ninety-eight patients characterized the care as good while
      seven felt it was poor.

PMID- 8885191
TI  - Quality assurance in Swiss University Hospitals: a survey among clinical
      department heads.
AB  - OBJECTIVE: To obtain information to help design and implement quality improvement
      programmes. DESIGN: Questionnaire survey. SETTING: Swiss University Hospitals.
      STUDY PARTICIPANTS: Clinical Department heads. MAIN OUTCOME MEASURES: Attitudes
      towards quality assurance and percentage of departments with procedures for
      measurement and improvement of structure, process and outcome of medical care.
      RESULTS: Among 138 departments responding, 69 indicated a designated person or
      group in charge of quality and 57 were involved in collaborative quality
      improvement programmes. Mortality data at the level of the department was
      unavailable to 33% of respondents, and data on adverse treatment effects to 67%
      of them. Most respondents (69%) favoured the use of outcome indicators for
      quality control; only 13% favoured indicators pertaining to process or structure
      of care. Among indicators of outcome, patient satisfaction was the preferred
      indicator (25% of respondents), followed by morbidity (16%) and mortality (12%)
      data. CONCLUSION: Although the quality of medical care in Switzerland enjoys an
      excellent reputation, this study highlights important gaps in the information
      system and the processes necessary to evaluate quality.

PMID- 8885192
TI  - Perinatal information system: a methodological proposal.
AB  - This article describes the development of an information system in perinatal
      care, designed for research into effectiveness-including analysis of the
      relationship between process and outcome- and for quality assurance purposes. The
      methodology for selecting perinatal problems, defining process content and
      indicators, specifying severity for control of confounding in the analysis of
      outcomes, and developing the recording format is outlined. The system and its
      data processing are described. Its utilization and limitations are also
      discussed.

PMID- 8885194
TI  - "Every defect is a treasure".

PMID- 8885193
TI  - Effectiveness and prognostic factors of success in 12 smoking cessation clinics
      in the hospitals of Assistance publique-Hopitaux de Paris.
AB  - We evaluated whether the location of a smoking cessation clinic in a hospital
      enhances the success rate compared to that found in the literature, regardless of
      the type of treatment. We assessed the results and identified prognostic factors
      of success in 12 smoking cessation clinics situated in 12 hospitals of the
      Assistance publique-Hopitaux de Paris (AP-HP). The clinics were included in the
      study after a call for participation. The response rate was 60%. The study design
      was prospective, multicentric and descriptive. The study lasted 9 months. Follow
      up took place 3 and 6 months after the first visit. The definition of success was
      self-reported total abstinence from cigarette smoking during the month preceding
      the 6-month follow-up. Success rate was 27%, failures were 66%, and 7% were lost
      to follow-up. Prognostic factors of success were not related to the hospital
      setting. We conclude that for a number of structural reasons that we explain,
      according to this study, the location of smoking cessation clinics in hospitals
      does not enhance their success rate compared to that found in the literature.

PMID- 8885195
TI  - Validity review of performance measures.
AB  - A structured process for evaluating the validity of performance measures is
      essential if the rates generated by these measures are to be relied upon for
      large-scale programmes to improve clinical care. In this evaluation process a
      panel of objective clinicians who were not involved in developing the performance
      measures examines the criteria, coding instructions, and coding form. The panel's
      job is to determine the degree to which a sample of patient records containing
      treatment elements that have been flagged for nonconformance to certain criteria
      are truly nonconformant. Modification of the performance measure according to the
      recommendations of the panel provides an important means of reducing measurement
      error by eliminating obvious sources of false positive findings. This article
      describes the procedures followed and the materials used to validate the
      performance measures developed for the project to Develop and Evaluate Methods
      for Promoting Ambulatory Care Quality (DEMPAQ), a research project contracted by
      the Health Care Financing Administration of the United States government [1-3].
      DEMPAQ is described in Fig. 1. In the DEMPAQ project, record review is conducted
      by entering data directly from patient ambulatory records into a computer system.
      Instructions for abstracting the data are displayed on the computer monitor.

PMID- 8885196
TI  - Distribution of aromatase-immunoreactive cells in the forebrain of zebra finches
      (Taeniopygia guttata): implications for the neural action of steroids and nuclear
      definition in the avian hypothalamus.
AB  - Cells immunoreactive for the enzyme aromatase were localized in the forebrain of
      male zebra finches with the use of an immunocytochemistry procedure. Two
      polyclonal antibodies, one directed against human placental aromatase and the
      other directed against quail recombinant aromatase, revealed a heterogeneous
      distribution of the enzyme in the telencephalon, diencephalon, and mesencephalon.
      Staining was enhanced in some birds by the administration of the nonsteroidal
      aromatase inhibitor, R76713 racemic Vorozole) prior to the perfusion of the birds
      as previously described in Japanese quail. Large numbers of cells immunoreactive
      for aromatase were found in nuclei in the preoptic region and in the tuberal
      hypothalamus. A nucleus was identified in the preoptic region based on the high
      density of aromatase immunoreactive cells within its boundaries that appears to
      be homologous to the preoptic medial nucleus (POM) described previously in
      Japanese quail. In several birds alternate sections were stained for
      immunoreactive vasotocin, a marker of the paraventricular nucleus (PVN). This
      information facilitated the clear separation of the POM in zebra finches from
      nuclei that are adjacent to the POM in the preoptic area-hypothalamus, such as
      the PVN and the ventromedial nucleus of the hypothalamus. Positively staining
      cells were also detected widely throughout the telencephalon. Cells were
      discerned in the medial parts of the ventral hyperstriatum and neostriatum near
      the lateral ventricle and in dorsal and medial parts of the hippocampus. They
      were most abundant in the caudal neostriatum where they clustered in the
      dorsomedial neostriatum, and as a band of cells coursing along the dorsal edge of
      the lamina archistriatalis dorsalis. They were also present in high numbers in
      the ventrolateral aspect of the neostriatum and in the nucleus taeniae. None of
      the telencephalic vocal control nuclei had appreciable numbers of cells
      immunoreactive for aromatase within their boundaries, with the possible exception
      of a group of cells that may correspond to the medial part of the magnocellular
      nucleus of the neostriatum. The distribution of immunoreactive aromatase cells in
      the zebra finch brain is in excellent agreement with the distribution of cells
      expressing the mRNA for aromatase recently described in the finch telencephalon.
      This widespread telencephalic distribution of cells immunoreactive for aromatase
      has not been described in non-songbird species such as the Japanese quail, the
      ring dove, and the domestic fowl.

PMID- 8885197
TI  - Neuronal development in the Drosophila compound eye: photoreceptor cells R1, R6,
      and R7 fail to differentiate in the retina aberrant in pattern (rap) mutant.
AB  - The compound eye of Drosophila is a reiterated pattern of 800 unit eyes known as
      ommatidia. In each ommatidium there are eight photoreceptor neurons (R1-R8) and
      an invariant number of accessory cells organized in a precise manner. In the
      developing eye, specification of cell fates is triggered by sequential inductive
      events mediated by cell-cell interactions. The R8 photoreceptor neuron is the
      first cell to differentiate and is thought to play a central role in the
      recruitment of the remaining photoreceptor cells. Our previous work demonstrated
      that mutations in the retina aberrant in pattern (rap) locus lead to abnormal
      pattern formation in the compound eye. Genetic mosaic experiments demonstrated
      that for normal retinal patterning to occur, rap gene function is required only
      in the photoreceptor cell R8. In this study we analyzed the R cell composition of
      developing as well as the adult eyes of rap mutants employing a variety of R cell
      specific markers. We show that in rap mutants, although some of the R8-specific
      markers show normal expression patterns, other aspects of the R8 cell
      differentiation are abnormal. In addition, the cells R1, R6, and R7 fail to
      differentiate properly in rap mutants. These results suggest that the rap gene
      encodes an R8-specific function that plays a role in the determination of the
      photoreceptor cells R1, R6, and R7.

PMID- 8885198
TI  - Reliability and validity of the physical disector method for estimating neuron
      number.
AB  - The physical disector was proposed as an unbiased and efficient means to estimate
      neuron number; however, the validity and reliability of this method have been
      examined only infrequently. Estimates of neuron number in the dorsal root ganglia
      (DRG) of bullfrogs (Rana catesbeiana) were compared to nucleolar counts based on
      3-dimensional reconstructions. Accuracy of disector estimates were not affected
      by size of the animal. Similarly, disector estimates were not systematically
      altered when area measurements were limited to cellular regions of the DRG versus
      inclusion of the entire cross-sectional area. However, the recommended protocol
      for applying the disector resulted in sampling errors that introduced
      considerable variability in repeated estimates of neuron number from a single
      ganglion. In addition to this lack of reliability, disector estimates were
      consistently lower than those obtained by means of a nucleolar counting method
      that was calibrated against 3-dimensional reconstructions of neuronal profiles.
      The systematic error of the disector method was greater when ganglia were cut
      parallel to the long axis of the DR than when they were cut perpendicular to this
      axis. Increasing the sample size beyond what was recommended increased the
      reliability of estimates obtained with the disector; however, the bias associated
      with the plane of section was not reduced. These results emphasize the need for
      empirical validation of methods used to estimate neuron number in the tissue to
      which they are to be applied.

PMID- 8885199
TI  - Synapse loss and axon retraction in response to local muscle degeneration.
AB  - During metamorphosis in the moth, Manduca sexta, the abdominal body-wall muscle
      DEO1 is remodeled to form the adult muscle DE5. As the larval muscle degenerates,
      its motoneuron loses its end plates and retracts axon branches from the
      degenerating muscle. Muscle degeneration is under the control of the insect
      hormones, the ecdysteroids. Topical application of an ecdysteroid mimic resulted
      in animals that produced a localized patch of pupal cuticle. Muscle fibers
      underlying the patch showed a gradient of degeneration. The motoneuron showed end
      plate loss and axon retraction from degenerating regions of a given fiber but
      maintained its fine terminal branches and end plates on intact regions. The
      results suggest that local steroid treatments that result in local muscle
      degeneration bring about a loss of synaptic contacts from regions of muscle
      degeneration.

PMID- 8885200
TI  - Parvalbumin, calbindin, and calretinin mark distinct pathways during development
      of monkey dorsal lateral geniculate nucleus.
AB  - Immunocyochemical labeling was applied to follow the developmental changes in the
      calcium-binding proteins parvalbumin (PV), calbindin D28k (CaB), and calretinin
      (CaR) during fetal and infant development of Macaca monkey dorsal lateral
      geniculate nucleus (LGN). For all three proteins, LGN cell body and retinal
      ganglion cell (RGC) axon labeling patterns changed temporally and spatially over
      development, and many of these were LGN laminar specific. CaR+ and CaB+ cells
      were present at the youngest age studied, fetal day 55 (F55). After lamination of
      the LGN occurred between F90 and F115, CaR+ and CaB+ neurons were specific
      markers for the S, intercalated, and interlaminar layers. Double label
      immunocytochemistry showed that all CaR+ cells contained CaB, and none contained
      GABA. CaR+ cell bodies decreased in number soon after birth so that adult LGN
      contained only a very small number of CaR+ cells. These patterns and cell counts
      indicated that a downregulation of CaR had occurred in the CaB+ population.
      Although CaB+ cell density in S and interlaminar zones declined in the adult,
      cell counts indicated that this is due to dilution of a stable population into a
      much larger nucleus during development. PV+ cells appeared at F85 only within the
      putative magnocellular (M) and parvocellular (P) layers, and PV remained a marker
      for these layers throughout development. Fetal PV cells also contained GABA,
      indicating that they were LGN interneurons. After birth, GABA-/PV+ cell numbers
      increased dramatically throughout the whole nucleus so that by the end of the
      first year, P and M layers were filled with PV+ cells. Their number and size
      indicated that these were the LGN projection neurons. Beginning at F66, bundles
      of PV+ axons occupied the anterior-middle LGN and filled the optic tract. Up to
      F101, PV+ synaptic terminals were restricted to Players, but after F132 labeling
      in M layers was heavier than in P layers. Axonal labeling for CaR began at F125.
      Prenatally CaR+ terminals were present mainly in P layers, whereas by postnatal 9
      weeks labeling in M layers much exceeded P layers. Axonal labeling for CaB was
      present at F132, but CaB+ terminals were observed only after birth with labeling
      always heavier in M than P layers. By postnatal 9 weeks, PV, CaR, and CaB were
      colocalized in the same axons and terminals. These experiments indicated that
      during development and in the adult LGN, both CaR and CaB were markers for the
      LGN neurons in the S and intercalated pathway. CaR was present transiently while
      CaB persisted into adulthood. PV was a M and P layer marker first for
      interneurons and later for projection cells. The complex temporal developmental
      patterns found in this study suggested that viewing PV, CaB, and CaR simply as
      calcium-buffering proteins severely underestimates their functional roles during
      visual system maturation.

PMID- 8885201
TI  - Acetylcholine receptor clustering associates with proteoglycan biosynthesis in C2
      variant and heterkaryon muscle cells.
AB  - Several lines of evidence have suggested roles for proteoglycans (PGs) in
      acetylcholine receptor (AChR) clustering on muscle cells. One line of evidence
      comes from the correlation between a defect in the biosynthesis of
      glycosaminoglycans (GAGs), the defining carbohydrates of PGs, and the failure of
      spontaneous AChR clustering in the S27 cell line, a genetic variant of the C2
      muscle cell line. Two approaches were used in the present study to investigate
      whether GAG and AChR clustering defects are causally linked. First, the formation
      of AChR clusters was examined in two more variant lines, S11 and S26, also
      isolated from the C2 muscle cell line on the basis of deficiencies in GAG
      biosynthesis. S11 and S26, like S27, are also defective in AChR clustering. Ion
      exchange analysis of the GAGs made by the S11, S26, and S27 lines revealed that
      the defects in GAG biosynthesis differ between the three lines. Second,
      heterokaryon myotubes formed between pairs of the GAG defective variants were
      tested for complementation in both AChR clustering and GAG biosynthesis. AChR
      clusters were conspicuous on individual heterokaryon myotubes, and GAG
      biosynthesis was restored to near wild type levels in the heterokaryon cultures.
      Complementation in GAG biosynthesis corroborates the biochemical data that the
      relevant mutations in the genetic variants are in different genes and establishes
      that the defects are not dominant. The consistent correlation between GAG defects
      and the failure of AChR clustering across three independent genetic variants and
      the complementary association of GAG biosynthesis with AChR clustering in
      heterokaryon myotubes argues against a chance association of the two phenotypes
      and for a causal relationship between PGs and AChR clustering. A prominent
      chondroitin sulfate peak correlated with AChR clustering in the heterokaryon
      cultures. This is consistent with earlier results suggesting that chondroitin
      sulfate in general is required for the spontaneous clustering of AChRs in C2
      cultures and further suggests that a particular chondroitin sulfate proteoglycan
      may be essential for the clustering process.

PMID- 8885202
TI  - In vivo observations of timecourse and distribution of morphological dynamics in
      Xenopus retinotectal axon arbors.
AB  - Changes in neuronal structure can contribute to the plasticity of neuronal
      connections in the developing and mature nervous system. However, the expectation
      that they would occur slowly precluded many from considering structural changes
      as a mechanism underlying synaptic plasticity that occurs over a period of
      minutes to hours. We took time-lapse confocal images of retinotectal axon arbors
      to determine the timecourse, magnitude, and distribution of changes in axon arbor
      structure within living Xenopus tadpoles. Images of axons were collected at
      intervals of 3 min, 30 min, and 2 h over total observation periods up to 8 h.
      Branch additions and retractions in arbors imaged at 3 or 30 min intervals were
      confined to shorter branches. Sites of additions and retractions were distributed
      throughout the arbor. The average lifetime of branches was about 10 min. Branches
      of up to 10 microns could be added to the arbor within a single 3 min observation
      interval. Observations of arbors at 3 min intervals showed rapid changes in the
      structure of branchtips, including transitions from lamellar growth cones to more
      streamlined tips, growth cone collaps, and re-extension. Simple branchtips were
      motile and appeared capable of exploratory behavior when viewed in time-lapse
      movies. In arbors imaged at 2-h intervals over a total of 8 h, morphological
      changes included longer branches, tens of microns in length. An average of 50% of
      the total branch length in the arbor was remodeled within 8 h. The data indicate
      that the elaboration of the arbor occurs by the random addition of branches
      throughout the arbor, followed by the selective stabilization of a small fraction
      of the new branches and the retraction of the majority of branches. Stabilized
      branches can then elongate and support the addition of more branches. These data
      show that structural changes in presynaptic axons can occur very rapidly even in
      complex arbors and can therefore play a role in forms of neuronal plasticity that
      operate on a timescale of minutes.

PMID- 8885203
TI  - Steroid accumulation in song nuclei of a sexually dimorphic duetting bird, the
      rufous and white wren.
AB  - This study tested the hypothesis that the relative proportion of neurons that are
      hormone sensitive in avian song control nuclei is related to the basic motor
      ability to sing, whereas the absolute number of such neurons is related to the
      complexity of song behavior. Either [3H]testosterone (T) or estradiol (E2) was
      injected into male and female rufous and white wrens (Thryothorus rufalbus), a
      tropical species in which females sing duets with males but have smaller song
      repertoires than males. Autoradiographic analysis indicated that there were no
      sex differences in the proportions of T or E2 target cells in two song nuclei:
      the high vocal center (HVC) and the lateral portion of the magnocellular nucleus
      of the anterior neostriatum (IMAN). The density of labeled cells per unit volume
      of tissue did not differ between the sexes in either song nucleus. Males have
      larger song nuclei, however, which is consistent with their more complex song
      behavior, and therefore have a greater total number of hormone-sensitive neurons
      in these regions than do females. Comparison of these results with measures of
      hormone accumulation in zebra finches, canaries, and bay wrens supports the
      hypothesis presented.

PMID- 8885204
TI  - Neurometamorphosis of the ear in the gypsy moth, Lymantria dispar, and its
      homologue in the earless forest tent caterpillar moth, Malacosoma disstria.
AB  - The adult gypsy moth, Lymantria dispar (Lymantriidae: Noctuoidea) has a pair of
      metathoracic tympanic ears that each contain a two-celled auditory chordotonal
      organ (CO). The earless forest tent caterpillar moth, Malacosoma disstria
      (Lasiocampidae: Bombycoidea), has a homologous pair of three-celled, nonauditory
      hindwing COs in their place. The purpose of our study was to determine whether
      the adult CO in both species arises from a preexisting larval organ or if it
      develops as a novel structure during metamorphosis. We describe the larval
      metathoracic nervous system of L. dispar and M. disstria, and identify a three
      celled chordotonal organ in the anatomically homologous site as the adult CO. If
      the larval CO is severed from the homologue of the adult auditory nerve (IIIN1b1)
      in L. dispar prior to metamorphosis, the adult develops an ear lacking an
      auditory organ. Axonal backfills of the larval IIIN1b1 nerve in both species
      reveal three chordotonal sensory neurons and one nonchordotonal multipolar cell.
      The axons of these cells project into tracts of the central nervous system
      putatively homologous with those of the auditory pathway in adult L. dispar.
      Following metamorphosis, M. disstria moths retain all four cells (three CO and
      one multipolar) while L. dispar adults possess two cells that service the
      auditory CO and one nonauditory, multipolar cell. We conclude that the larval
      IIIN1b1 CO is the precursor of both the auditory organ in L. dispar and the
      putative proprioceptor CO in M. disstria and represents the premetamorphic
      condition of these insects. The implications of our results in understanding the
      evolution of the ear in the Lepidoptera and insects in general are discussed.

PMID- 8885205
TI  - Short- and long-term effects of ciliary neurotrophic factor on androgen-sensitive
      motoneurons in the lumbar spinal cord.
AB  - Motoneuron death in the spinal nucleus of the bulbocavernosus (SNB) and the
      dorsolateral nucleus (DLN) of the lumbar spinal cord is androgen regulated. As a
      result, many more SNB and DLN motoneurons die in perinatal female rats than in
      males, whereas treatment of newborn females with androgen results in a permanent
      sparing of the motoneurons and their target muscles. We previously observed that
      a neurotrophic molecule, ciliary neurotrophic factor (CNTF), also arrests the
      death of SNB motoneurons and their target musculature, at least in the short
      term. The present study compares the short- and long-term consequences of
      perinatal CNTF treatment on motoneuron number in the SNB, the DLN, and the
      retrodorsolateral nucleus (RDLN), a motor pool in the lower lumbar cord that does
      not exhibit hormone-regulated cell death. Female pups were treated with CNTF or
      vehicle alone from embryonic day 22 through postnatal day 6 (P6). Motoneuron
      number in the each nucleus was then determined immediately after treatment on P7,
      or 10 weeks later (P77). CNTF treatment significantly elevated motoneuron number
      in the SNB and DLN on P7; the volume of SNB target muscles on P7 was also greater
      in the CNTF-treated group. These effects were transient, however, as motoneuron
      number and ratings of muscle size were not different in CNTF-and vehicle-treated
      females on P77. Perinatal CNTF treatment did not alter cell number in the RDLN at
      either age. The finding that effects of CNTF on SNB and DLN motoneuron number are
      short lived contrasts with the permanent effects of early androgen treatment, and
      has implications for molecular models of the actions of androgen and neurotrophic
      factors on the developing spinal cord.

PMID- 8885206
TI  - Feasibility of a clinic-based hypocaloric dietary intervention implemented in a
      school setting for obese children.
AB  - The objective of this study was to examine whether a protein-sparing modified
      fast diet and a hypocaloric balanced diet are effective in a clinic-based dietary
      intervention implemented in a school setting high-risk weight loss program for
      superobese (> or = 140% of their ideal body weight for height [IBW] children. A
      group of children from two suburban public schools in New Orleans, Louisiana were
      randomized to either dietary-intervention group and control group. Children were
      followed for 6 months. In the dietary-intervention-group, 12 of 44 superobese
      children [ages 8.8 to 13.4 years, weight 144% to 212% of IBW] volunteered to
      participate. In the control group, 7 of 19 superobese children [ages 9.4 to 12.9
      years, weight 140% to 195% of IBW] volunteered to participate. During the first 9
      weeks, 12 superobese children were placed on a 2520 to 3360 J (600 to 800 Cal)
      protein-sparing modified fast diet. Subsequently, the diets of all children were
      increased in a 3-month period 420 J (100 Cal) every 2 weeks until a 5040 J (1200
      Cal) per day balanced diet was attained. In both groups, height and weight were
      obtained at baseline, 10 weeks, and 6 months; and biochemical measurements were
      performed at baseline and 6 months. At 6 months the 12 superobese children on
      protein-sparing modified fast diet had a significant weight loss from baseline (
      5.6 +/- 7.1 kg, ANOVA p < 0.02); a significant decrease in percentage IBW (-24.3
      +/- 20%, ANOVA p < 0.002); and had positive growth velocity Z-score (1.3 +/- 1.6,
      ANOVA p < 0.05). Six children were not superobese at 6 months. At 6 months eight
      of 12 children were active participants and 11 of 12 children were followed.
      Decrease in blood pressure, as well as, downward trends in serum lipids were
      observed at 6 months. No clinical complications were observed. At 6 months, the 7
      control superobese children, when compared with baseline had gained weight (2.8
      +/- 3.1 kg, ANOVA p < 0.008); but had no significant change in percentage IBW (
      0.3 +/- 5.9%, ANOVA p = 0.61); and had no changes in growth velocity Z-score (0.1
      +/- 1.3, ANOVA p = 0.83). These children did not have any change in blood
      pressure and an upward trend in serum lipids were observed at 6 months. Protein
      sparing modified fast diet and a hypocaloric balanced diet appear to be effective
      in a group of superobese-school-age children in a medically supervised clinic
      based program implemented in a school setting over a 6-month period. The efforts
      of committed clinic staffs, school officials, peers, and family involvement were
      crucial to the success of this intervention program in promoting and maintaining
      weight loss over a 6-month period. Further research with a specific comparison of
      the hypocaloric diets with longer follow-up periods in the school setting is
      necessary. In the meantime, these diets should be used only with close medical
      supervision.

PMID- 8885207
TI  - Differences in body image and depression among obese women with and without binge
      eating disorder.
AB  - Obese individuals with binge eating disorder (BED) differ from obese non-binge
      eating (NBE) individuals in a number of clinically relevant ways. This study
      examined attitudinal responses to various measures of body image in women seeking
      obesity treatment, by comparing NBE participants (n = 80) to those with BED (n =
      48). It was hypothesized that women with BED would demonstrate greater
      attitudinal disturbance of body image compared to NBE individuals. It was further
      hypothesized that significant differences between groups would remain after
      statistically controlling for degree of depression. Consistent with the primary
      hypothesis, BED participants reported significantly increased attitudinal
      disturbance in body dissatisfaction and size perception compared to NBE
      participants. Although shared variance was observed between measures of
      depression and body image on some items, several aspects of increased body image
      disturbance remained after statistically controlling for depression. Treatment
      implications and recommendations for future research are discussed.

PMID- 8885208
TI  - A major gene for resting metabolic rate unassociated with body composition:
      results from the Quebec Family Study.
AB  - A major gene hypothesis for resting metabolic rate (RMR) was investigated using
      segregation analysis (POINTER) of data on families participating in Phase 2 of
      the Quebec Family Study. Complete analyses were conducted on RMR adjusted for
      age, and also on RMR adjusted for age and other covariates, primarily fat mass
      (FM) and fat-free mass (FFM). Prior to adjustment for covariates, support for a
      major gene hypothesis was equivocal-i.e., there was evidence for either a major
      gene or a multifactorial component (i.e., polygenic and/or familial environment).
      The multifactorial model was preferred over the major gene model, although the
      latter did segregate according to Mendelian expectations. However, after the
      effects of FM and FFM were accounted for, a major gene effect was unambiguous and
      compelling. The putative locus accounted for 57% of the variance, affected 7% of
      the sample, and led to high values of RMR. The lack of a significant
      multifactorial effect suggested that the familial etiology of RMR adjusted for FM
      and FFM was likely to be entirely a function of the major locus. Comparing the
      RMR results from pre- and post-adjustment for FM and FFM suggests a plausible
      hypothesis. We know from earlier studies in this sample that there is a putative
      major gene for FM and a major non-Mendelian effect for FFM. The current study
      leads us to speculate that: (1) the gene(s) affecting body size and body
      composition also may have an effect on RMR, and further (2) removal of the effect
      of the major gene(s) for body size and composition allowed for detection of an
      additional major gene affecting only the RMR. Thus, RMR appears to be an
      oligogenic trait.

PMID- 8885209
TI  - The relationship of body mass index to reproductive factors in pre- and
      postmenopausal African-American women with and without breast cancer.
AB  - To date, there are virtually no existing data on the relationship between
      obesity, menopausal status, and breast cancer in African-Americans. Therefore,
      the present study was designed to test the following hypotheses in an African
      American population: (1) there exists a positive association between BMI and
      breast cancer among postmenopausal women; (2) there exists an inverse association
      between BMI and breast cancer among premenopausal women; and (3) similar
      associations between BMI and reproductive factors exist for both pre- and
      postmenopausal breast cancer cases. The study population comprised 357 African
      American women (n = 193 breast cancer cases; n = 164 controls). No significant
      differences were observed between premenopausal cases and controls for BMI,
      obesity categories, and reproductive factors. Among the postmenopausal women, the
      cases had significantly lower weight and BMI levels than the controls. Age at
      first pregnancy and parity were significantly lower among postmenopausal cases
      than their controls. No significant associations were revealed between body mass
      index and breast cancer for pre- and postmenopausal women. In the present study,
      early age at menarche was the only reproductive factor that was an independent
      predictor of BMI for both pre- and postmenopausal women, irrespective of breast
      cancer status. Also, these findings strongly suggest the need to consider
      reproductive factors, particularly age at menarche, as a covariate of BMI and
      other obesity-related diseases.

PMID- 8885210
TI  - Effects of a personal trainer and financial incentives on exercise adherence in
      overweight women in a behavioral weight loss program.
AB  - Exercise is important for long-term weight loss, but few studies have examined
      ways to improve exercise adherence in overweight subjects participating in a
      behavioral weight loss program. This paper presents two studies, one conducted at
      the University of Pittsburgh and one at the University of Minnesota, that sought
      to improve exercise adherence by exerting more direct control over the
      environmental antecedents and consequences controlling exercise. Study 1
      investigated the use of a personal trainer who called participants regularly and
      met them at their home or office at scheduled times for a walk. Study 2
      investigated the effect of a lottery incentive for exercise adherence. In both
      studies, the effect of these manipulations was examined in the context of a 24
      week standard behavioral weight control program with three supervised exercise
      sessions per week. Neither intervention achieved statistically significant
      improvements in exercise adherence compared to control conditions, perhaps due in
      part to the limited statistical power of the studies. Future studies should focus
      on better understanding the barriers to exercise and designing behavioral
      interventions that address these barriers.

PMID- 8885211
TI  - Influence of androgenicity on adipocytes and precursor cells in female rats.
AB  - We examined the effects of overexposure of testosterone (T) on fat cell
      morphology and adipocyte precursor pools in inguinal and retroperitoneal fat
      depots of ovariectomized rats. In both tissues peripubertal T decreased weights
      without affecting adipocyte mean cell size or the size distribution profiles, but
      adipocyte number was decreased by 65% in the inguinal and by 38% in the
      retroperitoneal depots. Immunofluorescent flow cytometry utilizing a specific
      antibody to rat adipose tissue lipoprotein lipase was used to quantify regional
      precursor cell populations. T sharply reduced the percentages of differentiated
      and undifferentiated preadipocytes in the inguinal depot, from 43.2 +/- 5.3 to
      23.5 +/- 2.1% and from 57.7 +/- 4.0 to 43.6 +/- 5.3%, respectively, with a
      concomitant increase in fibroblasts from 1.6 to 32.9%. On the other hand, T had
      no effect on retroperitoneal preadipocyte pools. Perinatal androgenization
      exacerbated the decline in the inguinal weight (1.4 +/- 0.1 vs. 2.2 +/- 0.1g) but
      otherwise did not influence the actions of peripubertal T. Androgens may thus act
      in a tissue-specific manner to regulate fat cell growth potential in the femoral
      region in the female.

PMID- 8885212
TI  - Growth hormone treatment of hypophysectomized rats increases catecholamine
      induced lipolysis and the number of beta-adrenergic receptors in adipocytes: no
      differences in the effects of growth hormone on different fat depots.
AB  - Growth hormone (GH) has a lipolytic effect in adipose tissue but this effect may
      differ in adipose tissue from various fat depots. This latter possibility was
      investigated in the present study, in which the effects of GH in vivo on
      catecholamine-induced lipolysis and the number of beta-adrenergic receptors in
      isolated adipocytes from different fat depots of hypophysectomized rats were
      investigated. Female and male Sprague-Dawley rats were hypophysectomized or sham
      operated at 45 days of age. One week after the operation, hormonal replacement
      therapy with L-thyroxine and hydrocortisone acetate was given. In addition,
      groups of rats were treated with GH (1.33 mg/kg per day, given as two daily
      subcutaneous injections). After 1 week of hormonal treatment, adipocytes were
      isolated from the parametrial, epididymal and inguinal fat pads, and glycerol
      release after catecholamine-stimulation and 125I-cyanopindolol binding were
      measured. Hypophysectomy resulted in a marked decrease in the lipolytic response
      to catecholamines. GH treatment significantly increased catecholamine-induced
      lipolysis with similar effects in adipocytes from parametrial or epididymal and
      inguinal fat depots in both female and male rats. There were no differences
      between norepinephrine compared with isoproterenol-induced responses. 125I
      cyanopindolol binding was reduced after hypophysectomy and normalized by GH
      treatment, without differences between parametrial and inguinal adipose tissue
      regions. We conclude that the lipolytic effects of GH in the rat may partly be
      mediated by a stimulatory effect on beta-adrenergic receptors in adipocytes. In
      addition, GH exerted similar effect on catecholamine induced lipolysis and beta
      adrenergic receptors in adipocytes from parametrial, epididymal and inguinal fat
      depots.

PMID- 8885213
TI  - Correlations with self-reported weight loss in overweight U.S. adults.
AB  - The authors investigated two issues among overweight men and women in the U.S.:
      1) what is the influence of the self-expressed intention to lose weight in the
      presence of other potential predictors of loss and 2) what are easily
      identifiable predictors of intentional weight loss during a 1-year recall period.
      The sample consisted of 1996 overweight men (body mass index (BMI > or = 27.8
      kg/m2) and 2586 overweight women (BMI > or = 27.3 kg/m2) who answered questions
      regarding 1-year weight change in a Current Health Topic supplement of the
      population-based 1989 National Health Interview Survey. Of these overweight
      persons, 56.8% of men and 72.1% of women attempted to lose weight during the
      previous year. The most important characteristic associated with weight loss was
      the expressed intention itself. For any weight loss, the odds ratios (95%
      confidence intervals) for intention were 4.6 (3.6-5.9) for men and 3.8 (2.8-5.0)
      for women. Controlling for other factors reduced the odds only slightly, to 4.3
      for men and 3.5 for women. Among women, older age, having a greater frequency of
      blood pressure checks, and being in poorer health reduced the influence of intent
      as a predictor of loss. To address the second objective, the identification of
      predictors of intentional 1-year weight loss, analysis was restricted to
      overweight persons who attempted to lose weight. For both sexes, statistically
      significant predictors (p < 0.05) included never being married, smoking, higher
      BMI, being diabetic, and having a higher number of blood pressure checks. Being
      divorced or separated was predictive of weight loss in men only. Also, men were
      more likely to achieve weight loss than women. In conclusion, 1-year weight loss
      among the overweight was primarily a function of the intention to lose weight,
      although other factors contributed to determine whether weight loss was achieved.

PMID- 8885214
TI  - Obesity level and attrition: a response.

PMID- 8885215
TI  - Static theories in a dynamic world: a glucodynamic theory of food intake.

PMID- 8885216
TI  - Glucostatic mechanism of regulation of food intake. 1953.

PMID- 8885217
TI  - A fall in blood glucose level precedes meal onset in free-feeding rats. 1980.

PMID- 8885218
TI  - Distinct differences in the requirements for ribonucleoprotein complex formation
      on differentially regulated pre-edited mRNAs in Trypanosoma brucei.
AB  - Incubation of synthetic pre-edited mRNAs with extracts of Trypanosoma brucei
      mitochondria results in a family of specific, stable ribonucleoprotein (RNP)
      complexes that can be visualized by non-denaturing gel electrophoresis. We
      compared complexes that form with a substrate corresponding to the ATPase 6 (A6)
      pre-mRNA 3' region that is edited in both bloodstream and procyclic forms with a
      substrate corresponding to the 5' end of apocytochrome b (CYb) pre-mRNA that is
      edited only in procyclic (insect) forms. Four to five complexes are detected with
      both substrates and are specific since competition with homologous but not
      heterologous substrates prevents their formation. Formation of the CYb complex,
      however, is more sensitive to heterologous RNAs. In addition, the A6 substrate is
      more effective at preventing formation of CYb complexes than the converse. CYb
      complex formation is also more sensitive to divalent cation and salt
      concentrations and formation of one A6 component has a temperature optimum of 37
      degrees C while that of CYb is 27 degrees C.

PMID- 8885219
TI  - Amodiaquine accumulation in Plasmodium falciparum as a possible explanation for
      its superior antimalarial activity over chloroquine.
AB  - Amodiaquine is a 4-aminoquinoline antimalarial whose structure is similar to
      chloroquine. In contrast to the wealth of information available about chloroquine
      accumulation and its relationship to activity, little is known about the uptake
      characteristics of amodiaquine, a drug that is inherently more active against
      malaria parasites. In this study we have investigated the accumulation of
      amodiaquine in Plasmodium falciparum in vitro, in order to gain an insight into
      the mechanisms responsible for its superior activity over chloroquine. The
      driving force for parasite accumulation of the 4-aminoquinolines is proposed to
      be a transmembrane proton gradient maintained by a vacuolar ATPase. In the
      present study, amodiaquine accumulation was greatly reduced, at steady state, in
      the absence of glucose and at 0 degrees C indicating a clear energy dependence of
      uptake. Amodiaquine accumulation in Plasmodium falciparum was shown to be 2- to 3
      fold greater than chloroquine accumulation. This observation probably accounts
      for amodiaquine's greater inherent activity but is surprising given that
      amodiaquine is a weaker base than chloroquine. With this in mind we present
      evidence for an intraparasitic binding component in the accumulation of the 4
      aminoquinolines. Differences in binding affinity of this 'receptor' for
      amodiaquine and chloroquine may partially explain the greater accumulation and in
      vitro potency of amodiaquine compared to chloroquine.

PMID- 8885220
TI  - Biochemical analysis, gene structure and localization of the 24 kDa glutathione S
      transferase from Onchocerca volvulus.
AB  - Survival of Onchocerca volvulus, a pathogenic human filarial parasite, is likely
      to depend upon the detoxification activities of the glutathione S-transferases
      (GSTs). The 24 kDa O. volvulus GST, OvGST2, was expressed in a bacterial system
      and the recombinant protein was purified to homogeneity by affinity
      chromatography. Specific activities of the recombinant OvGST2 (rOvGST2) with a
      variety of substrates, and in the presence of inhibitors, were determined. With
      the universal substrate 1-chloro-2,4-dinitrobenzene, the specific activity of
      rOvGST2 was 2130 nmol min-1 mg-1. The rOvGST2 showed relatively limited selenium
      independent glutathione peroxidase activity, but secondary products of lipid
      peroxidation, namely members of the trans,trans-alka-2,4-dienal,trans-alk-2-enal
      and 4-hydroxyalk-2-enal series, were conjugated to glutathione via OvGST2
      dependent activity. The gene encoding the OvGST2 was isolated and the nucleotide
      sequence determined. The ovgst2 gene was found to possess seven exons with six
      intervening sequences, with all except one having consensus splice-site
      junctions. This intron/exon organisation of the ovgst2 gene is almost identical
      with those described for the mammalian Pi class GST genes, consistent with the
      protein structural evidence that the OvGST2 is related to the Pi class GSTs.
      Southern blot analysis with total parasite genomic DNA indicated a single copy
      gene, with a restriction pattern consistent with that of the isolated gene. The
      tissue distribution of the OvGST2 was examined in O. volvulus by
      immunohistochemistry and was shown to be distinct from that of the OvGST1. The
      OvGST2 was located throughout the syncytial hypodermis of male and female adult
      worms, as well as in the uterine epithelium. Microfilariae, and infective third
      stage larvae of O. volvulus, isolated from Simulium neavei, were immunopositive
      for OvGST2.

PMID- 8885221
TI  - Cloning and characterization of cDNAs encoding putative glutamate transporters
      from Caenorhabditis elegans and Onchocerca volvulus.
AB  - We report the identification and partial characterization of cDNAs encoding for
      putative glutamate transporters from the free-living nematode Caenorhabditis
      elegans and the filarial parasite Onchocerca volvulus. Glutamate transporters can
      be used as reliable markers for identifying cells and neurons that synaptically
      release glutamate and aspartate. An amplified PCR fragment containing a highly
      conserved amino acid heptamer found in all vertebrate glutamate transporters was
      used to screen a C. elegans cDNA library. Two full-length cDNA sequences from C.
      elegans were deduced from the isolated cDNA clones and RT-PCR products with the
      splice leader. The two C. elegans cDNA sequences differ by only 97 nucleotides at
      the 5' end. The C. elegans glutamate transporter gene glt-1 spans at least 2.9 kb
      of chromosomal DNA and possesses nine exons and eight introns. Primers directed
      to the CeGlt cDNA were used with O. volvulus first-strand cDNA to amplify and
      isolate the O. volvulus cDNA homolog. The C. elegans and O. volvulus glutamate
      transporters are 98% identical over 492 amino acids to each other and 52 to 58%
      identical to the mammalian glutamate transporters. Antibodies generated against
      partial coding regions of the C. elegans glutamate transporter recognized a
      protein of approximately 66 kDa in C. elegans and O. volvulus protein extracts.

PMID- 8885222
TI  - Repetitive peptide motifs in the cuticlin of Ascaris suum.
AB  - The cuticle of parasitic nematodes is composed of extracellular structural
      proteins. Over 90% of these proteins are collagenous molecules in the basal and
      median layers of the cuticle. The outermost layers of the cuticle, the
      epicuticle, is composed of non-collagenous proteins, that represent the
      structural surface of nematodes. In Ascaris these proteins have been termed
      'cuticlins'. While cuticular collagens have been well studied by both biochemical
      and genetic means, knowledge of the molecular structure of cuticlin components of
      parasitic nematodes is scarce. In the present paper we report on the production
      of monoclonal antibody 8.1, which is specific for cuticlin, but does not
      recognize collagen epitopes. We have screened a cDNA library derived from adult
      Ascaris suum mRNA of the hypodermal tissue underlying and synthesizing the
      cuticle. One positive cDNA clone encodes alanine-rich repetitive motifs, which
      are part of the insoluble cuticlin of the outermost layers of the epicuticle of
      Ascaris suum. This was shown in immunocytochemical experiments using specific
      polyclonal antisera raised against these motifs, expressed as fusion protein with
      glutathione S-transferase of the helminth Schistosoma japonicum. Comparison of
      the repetitive amino acid sequence with structural proteins of the nematode
      Caenorhabditis elegans and the insects Locusta migratoria and Ceratitis capitata
      revealed a minimal consensus motif.

PMID- 8885223
TI  - Telomere exchange can be an important mechanism of variant surface glycoprotein
      gene switching in Trypanosoma brucei.
AB  - Trypanosoma brucei undergoes antigenic variation by changing its Variant Surface
      Glycoprotein (VSG) coat. Although there are up to a thousand VSG genes, only one
      is transcribed at a time from a telomeric VSG expression site. Switching can
      involve DNA rearrangements exchanging the active VSG gene, or transcriptional
      activation of a new expression site and transcriptional silencing of the old one.
      Determining the mechanism mediating a switch has not always been easy, as the
      many virtually identical copies of VSG gene expression sites complicate
      transcriptional analysis. To overcome this problem, we have used bloodstream form
      T. brucei with a single copy VSG gene in an active expression site marked with a
      hygromycin resistance gene. We allowed these transformants to undergo switching
      of the active VSG gene, via three different experimental methods. We were able to
      select large numbers of switched trypanosomes from a single infected mouse using
      a new microtitre-dish based procedure developed for this purpose. The drug
      sensitivity of the switched trypanosomes allowed us to determine the
      transcriptional state of the marked expression site, and polymerase chain
      reaction (PCR) amplification was used to determine whether the single copy drug
      resistance gene and VSG gene present in the marked expression site had been
      retained. These studies showed that telomere exchange, which has been considered
      rare, can in some cases be an important mechanism of VSG gene switching. We
      describe 4 telomere exchange events between the active VSG 221 expression site
      and 4 different chromosomes.

PMID- 8885224
TI  - Identification of a family of Rab G-proteins in Plasmodium falciparum and a
      detailed characterisation of pfrab6.
AB  - As a first step towards developing a set of compartment-specific probes for
      studying protein trafficking in the malaria-infected erythrocyte, we describe
      here a family of Plasmodium falciparum Rab proteins. We characterise in detail P.
      falciparum Rab6 (PfRab6) a marker which in other cells is specific for the
      Golgi/trans Golgi network. Although PfRab6 mRNA is expressed throughout the
      intraerythrocytic cycle, maximal expression occurs at the trophozoite stage.
      Immunofluorescence microscopy shows that the distribution of PfRab6 changes
      during the final stages of parasite maturation, coalescing into multiple foci,
      each of which is associated with the nucleus of a forming daughter parasite.

PMID- 8885225
TI  - Effects of aphidicolin and hydroxyurea on the cell cycle and differentiation of
      Trypanosoma brucei bloodstream forms.
AB  - The effects of aphidicolin (APH) and hydroxyurea (HU) on the cell cycle and
      differentiation of Trypanosoma brucei bloodstream forms were studied. APH (0.1
      microgram ml-1) inhibited cell division, but did not inhibit DNA synthesis. Most
      of the cells were arrested in the G2 phase of the cell cycle, with each cell
      containing two kinetoplasts, but only one nucleus. Recovery of the arrested cells
      showed a 24-h lag period compared to controls. Higher concentrations of APH (1
      and 10 micrograms ml-1) were required to inhibit DNA synthesis, but the cells
      failed to resume growth after removal of the drug. Incubation of cells with HU
      (7.5 micrograms ml-1) did not inhibit DNA synthesis, but arrested cells after
      duplicating both the kinetoplast and the nucleus. Recovery from drug arrest also
      showed a 24-h lag period. We therefore conclude that neither APH nor HU arrests
      T. brucei at the G1/S phase boundary as anticipated. The mechanisms of cell cycle
      arrest by APH and HU are not through inhibition of DNA synthesis, but rather
      through unidentified pathways, leading to growth arrest prior to nuclear division
      and cytokinesis respectively. Since the arrested cells do not resume normal
      development immediately following drug removal, APH and HU should be regarded as
      unsuitable agents for synchronizing T. brucei bloodstream forms. T. brucei
      bloodstream forms arrested with either APH or HU differentiated normally into
      procyclic forms in vitro, indicating that a cycle of cell division is not
      required for initiation of differentiation, and that the process can be initiated
      and completed when cells are arrested at the G2/M and M/G1 phase boundaries.

PMID- 8885226
TI  - Cuticular collagen genes from the parasitic nematode Ostertagia circumcincta.
AB  - The nematode cuticle is a multifunctional structure whose roles include
      exoskeleton and barrier between the animal and its environment. It is an
      extracellular matrix which consists predominantly of small collagen-like
      proteins. For those species studied, these cuticular collagens are encoded by a
      multigene family. In the free living nematode Caenorhabditis elegans, this family
      has approximately 100 members. Our data indicate a gene family of similar size in
      the parasitic nematode Ostertagia circumcincta. We have characterised a pair of
      tandemly duplicated collagen genes from O. circumcincta, colost-1 and colost-2,
      which we believe to be the direct homologues of col-12 and col-13, a tandemly
      duplicated pair previously identified in C. elegans. The interspecies comparison
      of these homologues indicates regions of extreme conservation. We conclude that
      the gene duplication event that resulted in the creation of col-12 and col-13 in
      C. elegans is most likely the same duplication that generated colost-1 and colost
      2 in O. circumcincta, and thus this particular gene duplication precedes the
      divergence of the two species. These two nematode species are deeply diverged, O.
      circumcincta belonging to the order Strongylata and C. elegans to Rhabditata. The
      ability to identify direct homologues of individual cuticular collagen genes
      between deeply diverged species provides a powerful method for determining
      regions of structural importance in these small collagens. Characteristics that
      are conserved between homologues in divergent species, but not conserved with
      other members of the multigene family within one species, must relate to the
      specific function of that particular cuticular collagen.

PMID- 8885227
TI  - Ancylostoma caninum anticoagulant peptide: cloning by PCR and expression of
      soluble, active protein in E. coli.
AB  - Ancylostoma caninum Anticoagulant Peptide (AcAP) is the major anticoagulant
      activity present in extracts of adult Ancylostoma caninum hookworms. This 8.7 kDa
      protein is a potent and specific inhibitor of human coagulation factor Xa. Using
      PCR, we have isolated a cDNA encoding for AcAP from an adult A. caninum cDNA
      library. The 5' end of the AcAP cDNA was identified by reverse transcription PCR
      (RT-PCR) using A. caninum cDNA and a 5' primer corresponding to a nematode
      spliced leader sequence. The AcAP cDNA was expressed in E. coli using a
      prokaryotic expression vector, and the recombinant fusion protein (rAcAP) was
      purified to homogeneity using nickel resin affinity chromatography and reverse
      phase HPLC. Purified rAcAP is comparable to the native protein in inhibitor
      activity, with an apparent equilibrium inhibitory dissociation constant (Ki*) for
      the inhibition of factor Xa of 265 +/- 71 pM. The purified protein also prolongs
      the prothrombin and partial thromboplastic times of human plasma in a dose
      dependent manner.

PMID- 8885228
TI  - Leishmania herreri (Kinetoplastida; Trypanosomatidae) is more closely related to
      Endotrypanum (Kinetoplastida; Trypanosomatidae) than to Leishmania.

PMID- 8885229
TI  - Direct and indirect association of the small GTPase ran with nuclear pore
      proteins and soluble transport factors: studies in Xenopus laevis egg extracts.
AB  - Ran is a small GTPase that is required for protein import, mRNA export, and the
      maintenance of nuclear structures. To gain a better understanding of Ran's role
      in the nucleus, we have sought to use Xenopus egg extracts for the purification
      and characterization of proteins from egg extracts bound with a high affinity to
      a glutathione-S-transferase-Ran fusion protein (GST-Ran). We found that GST-Ran
      associates specifically with at least 10 extract proteins. We determined the
      identifies of six Ran-interacting proteins (Rips), and found that they include
      RanBP2/Nup358, Nup153, Importin beta, hsc70, RCC1, and RanBP1. On the basis of
      peptide sequence, a seventh Rip (p88) seems to be similar but not identical to
      Fug1/RanGAP1, the mammalian Ran-GTPase-activating protein. Gel filtration
      analysis of endogenous extract proteins suggests that Importin beta acts as a
      primary GTP-Ran effector. Both Ran and Importin beta are coimmunoprecipitated by
      anti-p340RanBP2 antibodies in the presence of nonhydrolyzable GTP analogues,
      suggesting that Ran-Importin beta complexes interact with p340RanBP2. Two other
      Rips, p18 and p88, are coprecipitated with p340RanBP2 in a nucleotide-independent
      manner. Analysis of the Ran-GTPase pathway in Xenopus extracts allows the
      examination of interactions between Ran-associated proteins under conditions that
      resemble in vivo conditions more closely than in assays with purified components,
      and it thereby allows additional insights into the molecular mechanism of nuclear
      transport.

PMID- 8885230
TI  - TGF beta-induced growth inhibition in primary fibroblasts requires the
      retinoblastoma protein.
AB  - Transforming growth factor beta (TGF beta) inhibits cell proliferation by
      inducing a G1 cell-cycle arrest. Cyclin/CDK complexes have been implicated in
      this arrest, because TGF beta treatment leads to inhibition of cyclin/CDK
      activity. We have investigated the role of the retinoblastoma protein (pRb) in
      TGF beta-induced growth arrest by using RB+/+ and RB-/- primary mouse embryo
      fibroblasts. In both of these cell types, TGF beta inhibits CDK4-associated
      kinase activity. However, whereas CDK2-associated kinase activity was completely
      inhibited by TGF beta in the wild-type cells, it was reduced only slightly in the
      RB mutant cells. In addition, at high-cell density the growth-inhibitory effects
      of TGF beta are no longer observed in the RB-/- cells; on the contrary, TGF beta
      treatment promotes the growth of these mutant fibroblasts. Thus, under certain
      cellular growth conditions, elimination of pRb transforms the growth-inhibitory
      effects of TGF beta into growth-stimulatory effects. These observations could
      help to explain why TGF beta is often found to enhance tumorigenicity in vivo and
      why inactivation of the RB gene leads to tumorigenesis.

PMID- 8885231
TI  - Mutagenic analysis of the destruction signal of mitotic cyclins and structural
      characterization of ubiquitinated intermediates.
AB  - Mitotic cyclins are abruptly degraded at the end of mitosis by a cell-cycle
      regulated ubiquitin-dependent proteolytic system. To understand how cyclin is
      recognized for ubiquitin conjugation, we have performed a mutagenic analysis of
      the destruction signal of mitotic cyclins. We demonstrate that an N-terminal
      cyclin B segment as short as 27 residues, containing the 9-amino-acid destruction
      box, is sufficient to destabilize a heterologous protein in mitotic Xenopus
      extracts. Each of the three highly conserved residues of the cyclin B destruction
      box is essential for ubiquitination and subsequent degradation. Although an
      intact destruction box is essential for the degradation of both A- and B-type
      cyclins, we find that the Xenopus cyclin A1 destruction box cannot functionally
      substitute for its B-type counterpart, because it does not contain the highly
      conserved asparagine necessary for cyclin B proteolysis. Physical analysis of
      ubiquitinated cyclin B intermediates demonstrates that multiple lysine residues
      function as ubiquitin acceptor sites, and mutagenic studies indicate that no
      single lysine residue is essential for cyclin B degradation. This study defines
      the key residues of the destruction box that target cyclin for ubiquitination and
      suggests there are important differences in the way in which A- and B-type
      cyclins are recognized by the cyclin ubiquitination machinery.

PMID- 8885232
TI  - The association of annexin I with early endosomes is regulated by Ca2+ and
      requires an intact N-terminal domain.
AB  - Annexin I is a member of a multigene family of Ca2+/phospholipid-binding proteins
      and a major substrate for the epidermal growth factor (EGF) receptor kinase,
      which has been implicated in membrane-related events along the endocytotic
      pathway, in particular in the sorting of internalized EGF receptors occurring in
      the multivesicular body. We analyzed in detail the intracellular distribution of
      this annexin by cell fractionation and immunoelectron microscopy. These studies
      used polyclonal as well as a set of species-specific monoclonal antibodies, whose
      epitopes were mapped to the lateral surface of the molecule next to a region
      thought to be involved in vesicle aggregation. Unexpectedly, the majority of
      annexin I was identified on early and not on multivesicular endosomes in a form
      that required micromolar levels of Ca2+ for the association. The specific
      cofractionation with early endosomes was also observed in transfected baby
      hamster kidney cells when the intracellular fate of ectopically expressed porcine
      annexin I was analyzed by using the species-specific monoclonal antibodies in
      Western blots of subcellular fractions. Interestingly, a truncation of the N
      terminal 26, but not the N-terminal 13 residues of annexin I altered its
      intracellular distribution, shifting it from fractions containing early to those
      containing late and multivesicular endosomes. These findings underscore the
      regulatory importance of the N-terminal domain and provide evidence for an
      involvement of annexin I in early endocytotic processes.

PMID- 8885233
TI  - Multiple classes of yeast mutants are defective in vacuole partitioning yet
      target vacuole proteins correctly.
AB  - In Saccharomyces cerevisiae the vacuoles are partitioned from mother cells to
      daughter cells in a cell-cycle-coordinated process. The molecular basis of this
      event remains obscure. To date, few yeast mutants had been identified that are
      defective in vacuole partitioning (vac), and most such mutants are also defective
      in vacuole protein sorting (vps) from the Golgi to the vacuole. Both the vps
      mutants and previously identified non-vps vac mutants display an altered vacuolar
      morphology. Here, we report a new method to monitor vacuole inheritance and the
      isolation of six new non-vps vac mutants. They define five complementation groups
      (VAC8-VAC12). Unlike mutants identified previously, three of the complementation
      groups exhibit normal vacuolar morphology. Zygote studies revealed that these vac
      mutants are also defective in intervacuole communication. Although at least four
      pathways of protein delivery to the vacuole are known, only the Vps pathway seems
      to significantly overlap with vacuole partitioning. Mutants defective in both
      vacuole partitioning and endocytosis or vacuole partitioning and autophagy were
      not observed. However, one of the new vac mutants was additionally defective in
      direct protein transport from the cytoplasm to the vacuole.

PMID- 8885234
TI  - Importance of glycolipid synthesis for butyric acid-induced sensitization to
      shiga toxin and intracellular sorting of toxin in A431 cells.
AB  - The human epidermoid carcinoma cell line A431 becomes highly sensitive to Shiga
      toxin upon treatment with butyric acid. This strong sensitization (> 1000-fold)
      is accompanied by an increase in the fraction of cell-associated toxin
      transported to the Golgi apparatus and to the endoplasmic reticulum (ER).
      Furthermore, our previous work showed that the length of the fatty acyl chain of
      Gb3, the Shiga toxin receptor, also was changed (longer fatty acids). We have not
      investigated the importance of this change by testing whether glycolipid
      synthesis is required for the changed intracellular sorting and the toxin
      sensitivity. We demonstrate here that inhibition of glycosphingolipid synthesis
      by inhibition of N-acyltransferase with fumonisin B1, by inhibition of
      glucosylceramide synthetase by PDMP or PPMP, or by inhibition of serine palmitoyl
      transferase by beta-fluoroalanine, inhibited the butyric acid-induced change in
      sensitivity and the increase in the fraction of cell-associated Shiga toxin
      transported to the Golgi apparatus and the ER. The block in butyric acid-induced
      sensitization caused by beta-fluoroalanine could be abolished by simultaneous
      addition of sphinganine or sphingosine. Thus, the data suggest that the fatty
      acyl chain length of glycosphingolipids is important for intracellular sorting
      and translocation of Shiga toxin to the cytosol.

PMID- 8885235
TI  - CDC37 is required for p60v-src activity in yeast.
AB  - Mutations in genes encoding the molecular chaperones Hsp90 and Ydj1p suppress the
      toxicity of the protein tyrosine kinase p60v-src in yeast by reducing its levels
      or its kinase activity. We describe isolation and characterization of novel p60v
      src-resistant, temperature-sensitive cdc37 mutants, cdc37-34 and cdc37-17, which
      produce less p60v-src than the parental wild-type strain at 23 degrees C.
      However, p60v-src levels are not low enough to account for the resistance of
      these strains. Asynchronously growing cdc37-34 and cdc37-17 mutants arrest in G1
      and G2/M when shifted from permissive temperatures (23 degrees C) to the
      restrictive temperature (37 degrees C), but hydroxyurea-synchronized cdc37-34 and
      cdc37-17 mutants arrest in G2/M when released from the hydroxyurea block and
      shifted from 23 to 37 degrees C. The previously described temperature-sensitive
      cdc37-1 mutant is p60v-src-sensitive and produces wild-type amounts of p60v-src
      at permissive temperatures but becomes p60v-src-resistant at its restrictive
      temperature, 38 degrees C. In all three cdc37 mutants, inactivation of Cdc37p by
      incubation at 38 degrees C reduces p60v-src-dependent tyrosine phosphorylation of
      yeast proteins to low or undetectable levels. Also, p60v-src levels are enriched
      in urea-solubilized extracts and depleted in detergent-solubilized extracts of
      all three cdc37 mutants prepared from cells incubated at the restrictive
      temperature. These results suggest that Cdc37p is required for maintenance of
      p60v-src in a soluble, biologically active form.

PMID- 8885236
TI  - Activation of the osmo-sensitive chloride conductance involves P21rho and is
      accompanied by a transient reorganization of the F-actin cytoskeleton.
AB  - Hypo-osmotic stimulation of human Intestine 407 cells rapidly activated
      compensatory CL- and K+ conductances that limited excessive cell swelling and,
      finally, restored the original cell volume. Osmotic cell swelling was accompanied
      by a rapid and transient reorganization of the F-actin cytoskeleton, affecting
      both stress fibers as well as apical ruffles. In addition, an increase in total
      cellular F-actin was observed. Pretreatment of the cells with recombinant
      Clostridium botulinum C3 exoenzyme, but not with mutant enzyme (C3-E173Q) devoid
      of ADP-ribosyltransferase activity, greatly reduced the activation of the osmo
      sensitive anion efflux, suggesting a role for the ras-related GTPase p21rho. In
      contrast, introducing dominant negative N17-p21rac into the cells did not affect
      the volume-sensitive efflux. Cell swelling-induced reorganization of F-actin
      coincided with a transient, C3 exoenzyme-sensitive tyrosine phosphorylation of
      p125 focal adhesion kinase (p125FAK) as well as with an increase in
      phosphatidylinositol-3-kinase (PtdIns-3-kinase) activity. Pretreatment of the
      cells with wortmannin, a specific inhibitor of PtdIns-3-kinase, largely inhibited
      the volume-sensitive ion efflux. Taken together, our results indicate the
      involvement of a p21rho signaling cascade and actin filaments in the activation
      of volume-sensitive chloride channels.

PMID- 8885237
TI  - The small GTP-binding proteins, Rac and Rho, regulate cytoskeletal organization
      and exocytosis in mast cells by parallel pathways.
AB  - In mast cells, activation of GTP-binding proteins induces centripetal
      reorganization of actin filaments. This effect is due to disassembly,
      relocalization, and polymerization of F-actin and is dependent on two small
      GTPases, Rac and Rho. Activities of Rac and Rho are also essential for the
      secretory function of mast cells. In response to GTP-gamma-S and/or calcium, only
      a proportion of permeabilized mast cells is capable of secretory response. Here,
      we have compared actin organization of secreting and nonsecreting cell
      populations. We show that the cytoskeletal and secretory responses are strongly
      correlated, indicating a common upstream regulator of the two functions. The
      secreting cell population preferentially displays both relocalization and
      polymerization of actin. However, when actin relocalization or polymerization is
      inhibited by phalloidin or cytochalasin, respectively, secretion is unaffected.
      Moreover, the ability of the constitutively active mutants of Rac and Rho to
      enhance secretion is also unaffected in the presence of cytochalasin. Therefore,
      Rac and Rho control these two functions by divergent, parallel signaling
      pathways. Cortical actin disassembly occurs in both secreting and nonsecreting
      populations and does not, by itself, induce exocytosis. A model for the control
      of exocytosis is proposed that includes at least four GTP-binding proteins and
      suggests the presence of both shared and divergent signaling pathways from Rac
      and Rho.

PMID- 8885240
TI  - Characterization and determination of the biological activities of noncleavable
      high molecular weight forms of inhibin A and activin A.
AB  - Recombinant expression of human alpha- and beta A-inhibin subunit cDNAs in
      mammalian 293 cells results in the secretion of 20-53K free alpha-subunit-derived
      products, 30-105K alpha beta A-inhibin dimers, and 24-110K beta A-activin dimers.
      The present study verifies that the wide variation in the size of these products
      is due to incomplete cleavage of the proteolytic processing sites and the
      differential glycosylation of the N-linked glycosylation site at amino acid
      number 302 in the alpha C-subunit. The identity of each of these products was
      established by mutagenesis of proteolytic processing sites and N-linked
      glycosylation sites, combined with the analysis of transfection products by
      immunoprecipitation and one- and two-dimensional SDS-PAGE (SDS/SDS-beta-ME).
      Transient expression of processing site mutants of the alpha- and beta A-subunits
      in 293 cells was used to generate microgram quantities of noncleavable 55K and
      65K inhibin dimers, and noncleavable 110K activin A dimers. The 55K and 65K
      inhibin A forms were purified and found to be fully biologically active in a rat
      pituitary cell bioassay. The 110K high molecular weight (HMW) form of human
      activin A failed to show any FSH-releasing activity in the pituitary assay. Since
      radioactively labeled 55K and 65K inhibin A and 110K activin A remained intact
      after incubation with rat pituitary cells for 72 h, there appears to be no
      conversion of these dimers to lower molecular weight forms by proteolytic
      cleavage at additional sites. These results show for the first time that 55K and
      65K inhibit A are intrinsically biologically active and do not require cleavage
      to the 32K form for activation. In contrast, cleavage of the 110K activin A
      precursor to the 24K form would appear to be necessary for activity.

PMID- 8885239
TI  - Identification of novel M phase phosphoproteins by expression cloning.
AB  - Using an expression cloning technique, we isolated cDNAs for eight M phase
      phosphoproteins (MPPs 4-11). We then used affinity-purified antibodies to fusion
      proteins to characterize the intracellular localization and some biochemical
      properties of these proteins and two others that we identified previously (MPPs 1
      2). Each antibody immunoprecipitated one or two protein species of a
      characteristic size ranging from 17,000 to 220,000 Da. Each MPP, when
      immunoprecipitated from lysates of M phase cells, was reactive with MPM2, a
      monoclonal antibody that recognizes a group of related M phase phosphorylation
      sites, including F-phosphoT-P-L-Q. This reactivity indicated that all the MPPS
      encoded genuine M phase phosphoproteins. When antibodies to the MPPS were used
      for immunofluorescence microscopy, each anti-MPP gave a characteristic pattern of
      localization. In interphase, several of the MPPs were nuclear proteins, whereas
      others were cytoplasmic or distributed throughout the cell. Three MPPS were
      strikingly localized to interphase structures: MPP7 to centers of DNA
      replication, MPP9 to the Golgi complex, and MPP10 to nucleoli. In mitosis, most
      of the MPPs were distributed throughout the cells. Further studies of the 10
      MPPs, most of which are previously undescribed, are expected to provide new
      understandings of the process of cell division.

PMID- 8885238
TI  - Telomerase regulation during entry into the cell cycle in normal human T cells.
AB  - Telomerase activity is involved in telomere length maintenance. Leukocytes,
      unlike many human somatic tissues, have detectable telomerase activity. These
      cells provide a normal human cell type in which to study telomerase. We studied
      the regulation of telomerase activity and the telomerase RNA component as
      leukocytes were stimulated to enter the cell cycle. In primary human leukocytes
      stimulated with phytohemagglutinin, telomerase activity increased > 10-fold as
      naturally quiescent cells entered the cell cycle. Antibodies to the T cell
      receptor (TCR)/CD3 complex and the costimulatory CD28 receptor induced telomerase
      activity in a T cell-enriched population of cells. Rapamycin, an
      immunosuppressant that blocks TCR/CD3 signal transduction pathways and cdk2
      activation, blocked telomerase induction. Hydroxyurea, an inhibitor of S phase,
      did not block cdk2 kinase activity or telomerase activation. In summary,
      telomerase is regulated in G1 phase as normal human T cells enter the cell cycle.

PMID- 8885241
TI  - Expression of alternatively spliced isoforms of the parathyroid hormone (PTH)/PTH
      related peptide receptor messenger RNA in human kidney and bone cells.
AB  - Using a PCR-based strategy, two variants of the PTH/PTH-related peptide (PTH-rp)
      receptor mRNA were identified in human kidney, SaOS-2 human osteoblast cells, and
      rat bone that are produced by alternative splicing of exons coding for the N
      terminal portion of the receptor. In the S-N3-E2 isoform, the exon coding the
      signal peptide (S) is spliced to an alternative 3'-acceptor site, producing a
      product respecting the reading frame, but in which the E1 exon is replaced by 12
      amino acids derived from the N3 intron. In the S-E2 isoform, in which the E1 exon
      is deleted by cassette exclusion, the reading frame is changed, but a truncated
      receptor may be produced by reinitiation of translation at an overlapping
      stop/start codon. After transfection of COS and Chinese hamster ovary cells with
      the originally described S-E1-E2 isoform and the two splice variants, active
      transcription of PTH/PTH-rp receptor mRNA was detected by RT-PCR in all cases.
      Cell lines transfected with the S-E1-E2 and S-N3-E2 isoforms displayed a 15- to
      25-fold and 2- to 3-fold increase, respectively, in cAMP content after
      stimulation with 2.4 x 10(-7) M human PTH(1-34), whereas cells transfected with
      the S-E2 isoform did not respond. PTH elicited an increase in intracellular
      calcium only in cells transfected with the S-E1-E2 isoform. Studies evaluating
      the surface expression of receptors using anti-human PTH/PTH-rp receptor
      antibodies and the ability of transfected cells to bind [125I]PTH-rp indicated
      that the low or absent responses to PTH stimulation resulted, at least in part,
      from low surface expression of the S-N3-E2 and S-E2 isoforms. These studies
      support the conclusion that exon E1 is extremely important in promoting surface
      expression of the PTH/PTH-rp receptor but indicate that isoforms lacking this
      exon can retain the ability to recognize PTH. The possible intracellular
      expression of these splice variants, which account for 15-20% of total PTH/PTH-rp
      receptor mRNA, needs to be evaluated.

PMID- 8885242
TI  - Redox-mediated activation of latent transforming growth factor-beta 1.
AB  - Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that
      orchestrates response to injury via ubiquitous cell surface receptors. The
      biological activity of TGF beta is restrained by its secretion as a latent
      complex (LTGF beta) such that activation determines the extent of TGF beta
      activity during physiological and pathological events. TGF beta action has been
      implicated in a variety of reactive oxygen-mediated tissue processes,
      particularly inflammation, and in pathologies such as reperfusion injury,
      rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly
      activated after in vivo radiation exposure, which also generates reactive oxygen
      species (ROS). In the present studies, the potential for redox-mediated LTGF beta
      activation was investigated using a cell-free system in which ROS were generated
      in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction.
      Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26%
      activation compared with that elicited by standard thermal activation. Metal
      catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta
      activation that matched or exceeded thermal activation. The efficiency of
      ascorbate activation depended on ascorbate concentrations and the presence of
      transition metal ions. We postulate that oxidation of specific amino acids in the
      latency-conferring peptide leads to a conformation change in the latent complex
      that allows release of TGF beta. Oxidative activation offers a novel route for
      the involvement of TGF beta in tissue processes in which ROS are implicated and
      endows LTGF beta with the ability to act as a sensor of oxidative stress and, by
      releasing TGF beta, to function as a signal for orchestrating the response of
      multiple cell types. LTGF beta redox sensitivity is presumably directed toward
      recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta
      activation that can be deleterious during disease mechanisms involving chronic
      ROS production.

PMID- 8885243
TI  - Stimulation of the P-450 side chain cleavage enzyme (CYP11A1) promoter through
      ras- and Ets-2-signaling pathways.
AB  - Expression of the ovine P-450 side-chain cleavage enzyme gene (CYP11A1) is
      stimulated by epidermal growth factor (EGF) through a pathway that involves c-Jun
      in JEG-3 placental cells. Growth factor signaling involves ras-dependent and ras
      independent signaling pathways, which in turn regulate gene transcription through
      related but distinct mitogen-activated protein kinase pathways (MAPKs) including
      the extracellular signal-regulated kinases (ERKs) and the stress-activated
      protein kinases (SAPKs). We investigated the intracellular signaling pathways
      governing EGF induction of the CYP11A1 promoter. EGF stimulation of the CYP11A1
      promoter (4-fold) was reduced 60% by a dominant negative mutant of ras (N17), and
      30-40% by antisense ras. EGF induced both ERK and SAPK activity in JEG-3 cells.
      EGF-induced CYP11A1 promoter activity was reduced 60% by the MEK1 inhibitor
      PD098059 and 50% by a dominant negative mutant of the ERK-specific regulator
      MEK1. In contrast, dominant negative mutants of the SAPK-specific activator,
      SEK1, induced a further increase in EGF-induced CYP11A1 promoter activity.
      Constitutively active mutants of ras (V12 or L61) increased CYP11A1 promoter
      activity 6- to 8-fold. Deletion of the EGF response element (EGF-RE) between -92
      and -77 bp reduced ras induction by 60%; however, a residual 3-fold induction
      remained through the proximal -77 bp. Mutation of the EGF-RE AP-1-like sequence
      in the context of the native promoter reduced CYP11A1 promoter activation by ras
      60%. The EGF-RE sequence was sufficient for 6-fold activation by ras in the
      context of an heterologous thymidine kinase promoter. Candidate transcription
      factor targets (c-Jun, c-Ets-2) for the ras-signaling cascade were examined for
      their effects on CYP11A1 promoter activity. Overexpression of c-Jun induced the
      CYP11A1 promoter through the EGF-RE; however, c-Ets-2 activation of the CYP11A1
      promoter (12-fold) required the proximal ras-responsive promoter sequences that
      are distinct from the EGF/MEK/c-Jun-responsive element. Induction of the CYP11A1
      promoter by EGF involves a ras/MEK1/AP-1-dependent pathway that is distinct from
      induction by ras/c-Ets-2.

PMID- 8885244
TI  - Effects of wild type and mutant estrogen receptors on DNA flexibility, DNA
      bending, and transcription activation.
AB  - We examined the ability of wild type (WT) estrogen receptor (ER) and mutant ERs
      to induce distortion and directed bends in DNA fragments containing estrogen
      response elements and then monitored the ability of these receptors to activate
      transcription. The ER mutants had either 108 (109-595 ER) or 175 (delta AB ER)
      amino acids deleted from the amino terminus; 42 (delta F ER) or 65 (1-530 ER)
      amino acids deleted from the carboxy terminus; or a single point mutation at
      amino acid 380 (glu-->gln) in the ER hormone binding domain (E380Q ER). Circular
      permutation analysis was used to determine the degree of distortion induced in
      estrogen response element-containing DNA fragments (65 degrees for WT ER and
      E380Q ER, 56 degrees for 109-595 ER, 54 degrees for delta AB ER, 63 degrees for
      delta F ER, and 60 degrees for 1-530 ER). Phasing analysis delineated the
      magnitude of directed DNA bends (8.3 degrees for WT ER, 6.9 degrees for 109-595
      ER, 6.5 degrees for delta AB ER, 10.6 degrees for delta F ER, 12.4 degrees for 1
      530 ER, and 10.2 degrees for E380Q ER) and demonstrated that the direction of the
      bend was always toward the major groove of the DNA helix. The ability of each
      receptor to induce transcription of an estrogen-responsive reporter plasmid
      (E380Q ER > WT ER = delta F ER > 109-595 ER > delta AB ER > 1-530 ER) was related
      to the ability of the receptor to induce appropriate distortion (63 degrees-65
      degrees) and directed DNA bending (8 degrees-10 degrees) angles and the presence
      of transcription activation functions AF-1 and AF-2. These studies suggest that
      ER-induced DNA bending is one part of a multistep process involved in regulating
      estrogen-responsive genes.

PMID- 8885245
TI  - Inhibition of p70/p85 S6 kinase activities in T cells by dexamethasone.
AB  - Glucocorticoids (GC) are potent immunosuppressive agents that interfere with
      interleukin-2 (IL-2)-dependent proliferation and IL-2 receptor signal
      transduction in T lymphocytes through complex mechanisms. Here we report that the
      basal activity, and IL-2- and phorbol ester-dependent activation of the p70/p85
      S6 kinases (referred to collectively as pp70S6k) are inhibited by the
      glucocorticoid dexamethasone (Dex) in CTLL-20 cells. This Dex-induced inhibition
      is time- and dose-dependent, appears to be the consequence of pp70S6k
      dephosphorylation, and requires ongoing transcription. Attempts to establish a
      link between Dex action and those of known pp70S6k-regulating agents such as
      phosphatidylinositol 3-kinase, protein kinase A-stimulating agents, calyculin A
      inhibited protein phosphatases, and rapamycin have been negative. Additional
      results with NIH3T3 cells suggest the existence of a T cell-specific blockade of
      pp70S6k by Dex. Implications are 2-fold: 1) pp70S6k inactivation may account for
      at least part of the immunosuppressive effects of GC in vivo, and 2) GC
      inactivation of pp70S6k is exerted through a novel, distinct mechanism that does
      not appear to be linked to any other known pp70S6k regulatory process.

PMID- 8885246
TI  - Cooperation between the human estrogen receptor (ER) and MCF-7 cell-specific
      transcription factors elicits high activity of an estrogen-inducible enhancer
      from the trout ER gene promoter.
AB  - The human estrogen receptor (hER) is expressed in breast cancer MCF-7 cells and
      plays a major role in tumorigenic processes. In this report, we demonstrate that
      MCF-7-specific factors can cooperate with the hER to increase its transactivation
      activity. We previously demonstrated that the rainbow trout ER (rtER) gene is up
      regulated by the rtER protein itself, through an enhancer that contains an
      imperfect estrogen-responsive element (FP1 area). By performing footprinting
      experiments, we have delineated two other regulatory regions (FP2 and FP3 areas)
      in the 0.2-kb enhancer. We show, by transient transfections, that hER poorly
      transactivates this enhancer in CHO-K1 and Ishikawa cells whereas, in MCF-7
      cells, transcriptional activation occurs at a level about 20-fold higher than
      when the enhancer estrogen-responsive element (FP1) is the only regulatory region
      included in the reporter gene. These results indicate that areas other than FP1
      are important regulatory sites of this enhancer. Site-directed mutagenesis
      demonstrated that the FP1 area is absolutely necessary for induction by estradiol
      as well as for basal activity of this enhancer in MCF-7 cells. Gel shift
      experiments showed that MCF-7 cells contain a factor that binds to the FP3 area
      and is poorly expressed in all other tested cell lines. As suggested by site
      directed mutagenesis and deletion experiments, this FP3-binding protein may
      enhance the hER transactivation ability in MCF-7 cells. These data reinforce the
      idea that cell-specific transcription factors cooperate with steroid receptors to
      achieve maximal induction of hormone-responsive genes.

PMID- 8885247
TI  - The C-terminal third of the human luteinizing hormone (LH) receptor is important
      for inositol phosphate release: analysis using chimeric human LH/follicle
      stimulating hormone receptors.
AB  - Gonadotropin and TSH receptors represent a subgroup of seven transmembrane
      spanning, G protein-coupled receptors with a large extracellular ligand-binding
      region. After ligand binding to their receptors, the majority of actions of
      gonadotropins and TSH are believed to be mediated by the cAMP-protein kinase A
      pathway. Although formation of inositol phosphates (IP) has been reported after
      stimulation of rodent gonadotropin receptors, activation of phospholipase C after
      ligand binding of human LH or FSH receptors has not been investigated. Human
      gonadotropin receptors were transiently expressed in 293 cells, and the agonist
      induced stimulation of IP formation was measured. The LH receptor responded to a
      saturating dose of human CG (hCG) with a 5.2-fold increase of IPs whereas the FSH
      receptor responded to a saturating dose of FSH with only a 50% increase. On the
      basis of these differences and in view of the homologous nature of the two
      gonadotropin receptors, chimeric receptors were constructed using domain transfer
      to identify the regions in the human LH receptor important for
      phosphatidylinositol hydrolysis. Chimeric receptors containing the entire
      extracellular region of the FSH receptor and the seven transmembrane region plus
      the cytoplasmic tail of the LH receptor responded to FSH treatment with a 4.7
      fold increase in IP accumulation. In contrast, the chimeric receptor with the
      extracellular region of the LH receptor and the TM region plus the cytoplasmic
      tail of the FSH receptor responded minimally (50%) to hCG treatment. When the C
      terminal third (from TM V to the cytoplasmic tail) of the FSH receptor was
      replaced with the LH receptor sequence, the chimeric receptor still responded to
      FSH treatment with a large (6.2-fold) increase in IP release, similar to that of
      the wild type LH receptor (to hCG), suggesting that C-terminal third of the human
      LH receptor confers IP signaling ability. This functional domain was further
      divided into two areas, namely TM V to TM VI and TM VII to the cytoplasmic tail.
      The chimeric receptors F(I-IV)L(V-VI)F(VII-C)R and F(I-VI)L-VII-C)R, in which
      these two regions of the FSH receptor were replaced by the corresponding
      sequences of the LH receptor, responded to FSH treatment with partial increases
      in phosphatidylinositol hydrolysis (2.0- and 3.7-fold, respectively).
      Furthermore, when TM VII and the cytoplasmic tail of the LH receptor were
      replaced with the corresponding sequence of the FSH receptor, this chimeric
      receptor showed a diminished (2.0-fold) response to hCG in IP release. For all
      the chimeric receptor constructs analyzed, overall expression, equilibrium
      binding constants, and adenyl cyclase activation were not altered. Thus, unlike
      studies using chimeric muscarinic and dopaminergic receptors in which the second
      and third intracellular loops were found to be important for IP signaling, the
      entire C-terminal third of the human LH receptor is important for IP release.
      Future analysis using the chimeric receptor approach should provide new
      information on the structure-function relationship of gonadotropin, TSH, and
      other seven transmembrane-spanning receptors.

PMID- 8885248
TI  - GRK2 and beta-arrestin 1 as negative regulators of thyrotropin receptor
      stimulated response.
AB  - Arrestins are regulatory proteins for a number of G-coupled receptors. The
      binding of arrestin to receptor phosphorylated by G protein-coupled receptor
      kinase (GRK) quenches the activation of the G protein, thus resulting in receptor
      homologous desensitization. We have previously shown that the levels of beta
      arrestin1 are regulated by intracellular cAMP and proposed that this may
      represent one homeostatic mechanism with which to regulate some cellular
      responses. To test this hypothesis, we focused on the TSH receptor using a rat
      thyroid cell line, FRTL5. We found that beta-arrestin1 is the only detectable
      isoform of arrestin expressed in FRTL5 and that its expression is regulated by
      TSH. To investigate the possible role of GRK2/beta-arrestin1 machinery in the
      mechanism of TSH receptor homologous desensitization, we used a cotransfection
      approach. The TSH-induced cAMP accumulation in COS7 cells transfected with TSH
      receptor was reduced by 35-45% when cotransfected with GRK2 and/or beta
      arrestin1, indicating that the TSH receptor can be regulated by a GRK/arrestin
      mechanism. This raised the hypothesis that TSH increases the levels of beta
      arrestin1, which in turn could regulate the TSH stimulation. To test this point a
      FRTL5-derived cell line overexpressing beta-arrestin1 was generated. In these
      cells the TSH-stimulated cAMP accumulation and, more importantly, the mitogenic
      activity were substantially blunted. Our results show that TSH receptor
      stimulated cAMP accumulation and cell proliferation can be controlled by a
      GRK2/beta-arrestin1 mechanism.

PMID- 8885249
TI  - Determination of residues important in hormone binding to the extracellular
      domain of the luteinizing hormone/chorionic gonadotropin receptor by site
      directed mutagenesis and modeling.
AB  - The LH/CG receptor (LH/CG-R) belongs to the family of glycoprotein hormone G
      protein-coupled receptors. The extracellular domain of LH/CG-R is associated with
      high ligand-binding affinity and contains leucine-rich repeats (LRRs). With the
      goal of identifying essential amino acid residues involved in ligand binding, we
      replaced several conserved ionizable residues in the rat LH/CG-R with ones of
      opposite charge. The expression of these mutants was assessed by binding studies
      and Western blots after COS-7 cells were transiently transfected with wild type
      and mutant receptor cDNAs. The charge inversion of each of Lys40, Lys104, Asp118,
      Glu132, and Asp135 with Asp or Lys resulted in no detectable human CG binding in
      intact or solubilized cells; as control, a Lys40-->Arg replacement yielded a
      mutant with characteristics of the wild type receptor. Western analysis showed
      that the Lys40-->Arg mutant expressed at a level comparable to that of wild type
      receptor and, like wild type, exhibited a predominant immunoreactive mature form
      of LH/CG-R. Each of the five charge inversion mutants expressed at a lower level
      than wild type as assessed by immunoreactivity, and the levels of the Lys40-->Asp
      and Glu132-->Lys mutants were particularly low. The ratio of the mature to
      immature form of the receptor was high, i.e. like that of wild type, for the
      Glu132-->Lys and Asp135-->Lys replacements; the three other charge inversion
      mutants exhibited less mature than immature forms of the receptor. To aid in
      interpreting these results, we developed a model incorporating residues 27-235 of
      the extracellular domain of the rat LH/CG-R based on the crystal structure of the
      porcine ribonuclease inhibitor. Sequence homology and alignment revealed nine
      LRRs, with flanking cysteine clusters as found in a number of LRR proteins. Our
      model suggested that the Lys replacements of Glu132 and Asp135, i.e. those
      mutants that formed mature receptors, would disrupt the regional negative charge
      of the receptor. We propose that these residues are either directly involved in
      hormone binding or indirectly by disruption of the charge of an important binding
      surface.

PMID- 8885250
TI  - Interferon alpha, GM2 antigen and melanoma immunotherapy.

PMID- 8885251
TI  - Type 1 diabetes gets the genomics treatment.

PMID- 8885252
TI  - Hepatocellular carcinoma and p53 gene therapy.

PMID- 8885253
TI  - Cancer susceptibility genes and molecular carcinogenesis. American Association
      for Cancer Research Special Conference: Cancer Susceptibility Genes and Molecular
      Carcinogenesis.
AB  - As elaborated by Nobel Laureate Harold Varmus (Director of the National
      Institutes of Health, Bethesda, MD, USA) in his Keynote address, future studies
      must not only continue to expand our repertoire of genetic determinants of cancer
      susceptibility by identifying new cancer susceptibility genes, but most also now
      begin to address the function of these genes and their roles in the process of
      tumor development. Key areas for future investigation in this field, identified
      at the meeting, were: (1) understanding how susceptibility genes are altered in
      cancer cell physiology, (2) elucidating the function of these genes in the
      biochemistry of cellular signaling pathways; and (3) improving our ability to use
      this information to extrapolate basic oncology research to the clinic. At this
      meeting, the fields of molecular carcinogenesis, DNA repair and human genetics
      were very successfully integrated. These fields have converged in the areas of
      cell cycle control and genetic susceptibility, and this meeting capitalized on
      this convergence to highlight recent progress in these areas. Key areas for
      future research were also emphasized, including the need to apply the rapidly
      emerging information from these fields towards developing novel therapeutic
      modalities to treat and prevent cancer.

PMID- 8885254
TI  - Randomization in clinical trials and experimental molecular medicine.
AB  - Randomization has become a standard procedure for clinical trial design, and is
      also widely used in other areas of biological research. This article will examine
      the reasons why randomization has become a sine qua non in some areas, yet
      remains far less widely adopted in experimental studies of molecular medicine.
      Should randomization be used routinely in the design of most laboratory
      experiments?

PMID- 8885255
TI  - Spinal muscular atrophy: resources available on the World Wide Web.

PMID- 8885256
TI  - The role of heat shock proteins in protection and pathophysiology of the arterial
      wall.
AB  - The arterial wall is an integrated functional component of the circulatory system
      that is continually remodelling in response to various stressors, including
      localized injury, toxins, smoking and hypercholesterolaemia. These stimuli
      directly or indirectly cause changes in blood pressure and damage to the vessel
      wall, and eventually induce arterial stiffness and obstruction. To maintain the
      homeostasis of the vessel wall, the vascular cells produce a high level of stress
      proteins, also known as heat shock proteins, which protect against damage during
      haemodynamic stress. However, an immune reaction to heat shock proteins might
      contribute to the development of atherosclerosis. We hypothesize that the
      induction of heat shock proteins is beneficial in the arterial wall's response to
      stress but is harmful in certain other circumstances.

PMID- 8885257
TI  - Inherited retinal degeneration: exceptional genetic and clinical heterogeneity.
AB  - The function of the retina is to detect light and to send appropriate signals to
      the brain in response. Inherited diseases that cause the retina to degenerate,
      leading to either partial or total blindness, affect approximately 1 in 3000
      people. Rapid progress is being made in identifying the genetic causes of common,
      inherited retinal diseases, such as retinitis pigmentosa and macular
      degeneration, as well as some of the rare forms of retinal disease. Linkage
      studies of large families and candidate-gene screening of known retinal genes
      have already identified 59 independent genetic loci that can cause retinal
      degeneration. The astounding genetic and clinical heterogeneity that is being
      revealed is a 'nightmare' for those interested in molecular diagnostics but, at
      the same time, provides great insight into functional aspects of the normal
      retina.

PMID- 8885258
TI  - Familial hypertrophic cardiomyopathy: diagnostic and therapeutic implications of
      recent genetic studies.
AB  - Familial hypertrophic cardiomyopathy is the first primary cardiomyopathy to have
      yielded to the techniques of modern molecular genetics. In the past few years,
      four genes responsible for this disease have been identified, all of which code
      for sarcomeric structural proteins. In addition, structure-function analysis and
      genotype-phenotype correlation studies have shed significant light on the
      molecular basis of this disease. It is hoped that within the next few years the
      application of molecular genetic tools will not only facilitate the diagnosis of
      hypertrophic cardiomyopathy but will also provide prognostic and therapeutic
      stratification for more definitive therapy.

PMID- 8885259
TI  - Xenograft model systems for human melanoma.
AB  - Human melanoma cells inoculated intradermally into congenitally immune-deficient
      mice initiate angiogenesis and give rise to tumors with a human parenchyma and a
      murine stroma. These tumors are similar to the donor patients' tumors with
      respect to histological appearance, karyotype and molecular pathology. The
      cellular treatment sensitivities and the organ-specific metastatic patterns of
      the donor patients' tumors are also retained after xenotransplantation.
      Consequently, human melanoma xenografts are exciting experimental models that
      show great promise for future studies of the molecular biology, angiogenesis,
      pathophysiology, treatment sensitivity and metastatic behavior of malignant
      melanoma.

PMID- 8885260
TI  - Back to log phase: sigma S as a global regulator in the osmotic control of gene
      expression in Escherichia coli.
AB  - It is now well established that the sigma S subunit of RNA polymerase is a master
      regulator in a complex regulatory network that governs the expression of many
      stationary-phase-inducible genes in Escherichia coli. In this review, more recent
      findings will be summarized that demonstrate that sigma S also acts as a global
      regulator for the osmotic control of gene expression, and actually does so in
      exponentially growing cells. Thus, many sigma S-dependent genes are induced
      during entry into stationary phase as well as in response to osmotic upshift. K+
      glutamate, which accumulates in hyperosmotically stressed cells, seems to
      specifically stimulate the activity of sigma S-containing RNA polymerase at sigma
      S-dependent promoters. Moreover, osmotic upshift results in an elevated cellular
      sigma S level similar to that observed in stationary-phase cells. This increase
      is the result of a stimulation of rpoS translation as well as an inhibition of
      the turnover of sigma S, which in exponentially growing non-stressed cells is a
      highly unstable protein. Whereas the RNA-binding protein HF-I, previously known
      as a host factor for the replication of phage Q beta RNA, is essential for rpoS
      translation, the recently discovered response regulator RssB, and ClpXP protease,
      have been shown to be required for sigma S degradation. The finding that the
      histone-like protein H-NS is also involved in the control of rpoS translation and
      sigma S turnover, sheds new light on the function of this protein in
      osmoregulation. Finally, preliminary evidence suggests that additional stresses,
      such as heat shock and acid shock, also result in increased cellular sigma S
      levels in exponentially growing cells. Taken together, sigma S function is
      clearly not confined to stationary phase. Rather, sigma S may be regarded as a
      sigma factor associated with general stress conditions.

PMID- 8885261
TI  - The Clp ATPases define a novel class of molecular chaperones.
AB  - The Clp ATPases were originally identified as a regulatory component of the
      bacterial ATP-dependent Clp serine proteases. Proteins homologous to the
      Escherichia coli Clp ATPases (ClpA, B, X or Y) have been identified in every
      organism examined so far. Recent data suggest that the Clp ATPases are not only
      specificity factors which help to 'present' various protein substrates to the
      ClpP or other catalytic proteases, but are also molecular chaperones which can
      function independently of ClpP. This review discusses the recent evidence that
      the Clp ATPases are indeed molecular chaperones capable of either repairing
      proteins damaged during stress conditions or activating the initiation proteins
      for Mu, lambda or P1 DNA replication. A mechanism is suggested to explain how the
      Clp ATPases 'decide' whether to repair or destroy their protein substrates.

PMID- 8885262
TI  - Role of the periplasmic domain of the Escherichia coli NarX sensor-transmitter
      protein in nitrate-dependent signal transduction and gene regulation.
AB  - The narX, narQ and narL genes of Escherichia coli encode a nitrate-responsive two
      component regulatory system that controls the expression of many anaerobic
      electron-transport- and fermentation-related genes. When nitrate is present, the
      NarX and NarQ sensor-transmitter proteins function to activate the response
      regulator protein, NarL, which in turn binds to its DNA-recognition sites to
      modulate gene expression. The sensor-transmitter proteins are anchored in the
      cytoplasmic membrane by two transmembrane domains that are separated by a
      periplasmic region of approximately 115 amino acids. In this study we report the
      isolation and characterization of narX* (star) mutants that constitutively
      activate nitrate reductase (narGHJI) gene expression and repress fumarate
      reductase (frdABCD) gene expression when no nitrate is provided for the cell. An
      additional narX mutant was identified that has lost its ability to respond to
      environmental signals. Each narX defect was caused by a single amino acid
      substitution within a conserved 17 amino acid sequence, called the 'P-box', in
      the periplasmic exposed region of the NarX protein. As a result, DNA binding is
      then 'locked-on' or 'locked-off' to give the observed pattern of gene expression.
      Diploid analysis of these narX mutants showed that a NarX P-box mutant which
      conferred a 'locked-on' phenotype was trans dominant over wild-type NarX. Both
      were also trans dominant over the NarX P-box mutant which conferred a 'locked
      off' phenotype. Certain narX P-box mutations, when combined with a narX 'linker'
      region mutation, were recessive to the NarX linker mutation. Finally, a truncated
      form of the NarX protein that lacked the periplasmic and membrane regions also
      showed a 'locked-on' phenotype in vivo. Thus, the periplasmic and membrane
      domains are essential for signal transduction to NarL. From these findings, we
      propose that nitrate is detected in the periplasmic space of the cell, and that a
      signal-transduction event through the cytoplasmic membrane into the interior of
      the cell modulates the NarX-dependent phosphorylation/dephosphorylation of NarL.

PMID- 8885263
TI  - Two-stage regulation of an anti-sigma factor determines developmental fate during
      bacterial endospore formation.
AB  - During endospore formation in Bacillus subtilis an asymmetric division produces
      two cells, forespore and mother cell, which follow different developmental paths.
      Commitment to the forespore-specific developmental path is controlled in part by
      the activation of the forespore-specific RNA polymerase sigma factor, sigma F.
      Activity of sigma F is inhibited in the mother cell by the anti-sigma factor
      SpoIIAB. In the forespore, sigma F directs transcription of the structural gene
      for sigma G. However, sigma G does not become active until after engulfment of
      the forespore is complete. This sigma G activity is dependent upon the products
      of the spoIIIA operon. We showed that sigma G is present but mostly inactive in a
      spoIIIA mutant. We also demonstrated that the anti-sigma factor SpoIIAB can bind
      to sigma G in vitro. Moreover, a mutant form of sigma G that binds SpoIIAB
      inefficiently in vitro was shown to function independently of SpoIIIA during
      sporulation. These and previously reported results support a model in which
      SpoIIAB functions as an inhibitor of sigma G activity during sporulation.
      Therefore, we propose that the anti-sigma factor SpoIIAB antagonizes both sigma F
      and sigma G activities, and that this antagonism is relieved in the forespore in
      two stages. In the first stage, which follows septation, a SpoIIAA-dependent
      mechanism partially relieves SpoIIAB inhibition of sigma F activity in the
      forespore. In the second stage, which follows forespore engulfment, a SpoIIIA
      dependent process inactivates SpoIIAB in the forespore, resulting in the
      activation of sigma G.

PMID- 8885264
TI  - Identification of sigma S-dependent genes associated with the stationary-phase
      acid-resistance phenotype of Shigella flexneri.
AB  - Shigella flexneri grown to stationary phase has the ability to survive for
      several hours at pH 2.5. This acid resistance, which may contribute to the low
      infective dose associated with shigellosis, is dependent upon the expression of
      the stationary-phase-specific sigma factor sigma S. Using random TnphoA and
      TnlacZ mutagenesis we isolated five acid-sensitive mutants of S. flexneri, which
      had lost their ability to survive at pH 2.5 for 2 h in vitro. Each transposon
      insertion with flanking S. flexneri DNA was cloned and sequenced. Database
      searches indicated that two TnlacZ mutants had an insertion within the hdeA gene,
      which is the first gene in the hdeAB operon. Acid resistance was restored in one
      of these mutants by a plasmid carrying the entire hdeAB operon. Further sequence
      analysis from the remaining TnlacZ and two TnphoA mutants demonstrated that they
      all had insertions within a previously unidentified open reading frame (ORF),
      which is directly downstream from the gadB gene. This putative ORF encodes a
      protein that has homology to a number of inner membrane amino acid antiporters. A
      1.8 kb polymerase chain reaction (PCR) product containing this gene was cloned,
      which was able to restore acid resistance in each mutant. These fusions were
      induced during entry into late exponential phase and were positively regulated by
      RpoS. We confirmed that the expression of the acid-resistance phenotype in
      acidified minimal media was dependent upon the supplementation of glutamic acid
      and that this glutamate-dependent system was RpoS regulated. Southern
      hybridization revealed that both the gadC and hdeAB loci are absent in
      Salmonella. An rpoS deletion mutant of S. flexneri was also constructed to
      confirm the important role played by this gene in acid resistance. This rpoS-
      derivative was extremely acid sensitive. Two-dimensional gel electrophoresis of
      this mutant revealed that it no longer expressed 27 proteins in late log phase
      that were present in its isogenic parent. These data indicate that the expression
      of acid resistance in S. flexneri may be multifactorial and involve proteins
      located at different subcellular locations.

PMID- 8885265
TI  - Regulation of competence development and sugar utilization in Haemophilus
      influenzae Rd by a phosphoenolpyruvate:fructose phosphotransferase system.
AB  - Changes in intracellular cAMP concentration play important roles in Haemophilus
      influenzae, regulating both sugar utilization and competence for natural
      transformation. In enteric bacteria, cAMP levels are controlled by the
      phosphoenolpyruvate:glycose phosphotransferase system (PTS) in response to
      changes in availability of the preferred sugars it transports. We have
      demonstrated the existence of a simple PTS in H. influenzae by several methods.
      We have cloned the H. influenzae ptsI gene, encoding PTS Enzyme I; genome
      analysis locates it in a pts operon structurally homologous to those of enteric
      bacteria. In vitro phosphorylation assays confirmed the presence of functional
      PTS components. A ptsI null mutation reduced fructose uptake to 1% of the wild
      type rate, and abolished fructose fermentation even when exogenous cAMP was
      provided. The ptsI mutation also prevented fermentation of ribose and galactose,
      but utilization of these cAMP-dependent sugars was restored by addition of cAMP.
      In wild-type cells the non-metabolizable fructose analogue xylitol prevented
      fermentation of these sugars, confirming that the fructose PTS regulates cAMP
      levels. Development of competence under standard inducing conditions was reduced
      250-fold by the ptsI mutation, unless cells were provided with exogenous cAMP.
      Competence is thus shown to be under direct nutritional control by a fructose
      specific PTS.

PMID- 8885266
TI  - Activation of stable DNA replication in rapidly growing Escherichia coli at the
      time of entry to stationary phase.
AB  - The conditions are described in which DNA replication can occur, in the absence
      of protein synthesis, in wild-type Escherichia coli cells. Chromosome
      replication, which is normally inhibited by addition of chloramphenicol, becomes
      resistant to this drug after nutritional shiftup, e.g. from minimal medium to
      Luria broth. This replication activity appears transiently when nutritionally
      upshifted cells enter stationary phase. The activity strictly requires recA+, but
      it is independent of recB+ and dnaA+. It can occur in the absence of concomitant
      transcription. Activation of the replication does not result from induction of
      the SOS response. As the characteristics of this DNA replication resemble those
      of the previously characterized stable DNA replication, it is termed nutritional
      shiftup-activatable stable DNA replication, nSDR. Possible mechanisms of the
      activation of nSDR in rapidly growing cells at the time of entry to stationary
      phase are discussed.

PMID- 8885267
TI  - Cloning and characterization of bfpTVW, genes required for the transcriptional
      activation of bfpA in enteropathogenic Escherichia coli.
AB  - Expression of the bundle-forming pilus (BFP) of enteropathogenic Escherichia coli
      (EPEC) is regulated at the transcriptional level by growth phase, temperature,
      calcium and ammonium. Genes required for the transcriptional activation of bfpA
      were localized to a 1.8 kb fragment of the enteroadherent factor (EAF) plasmid of
      EPEC that is separated from the bfp operon by 6 kb. Within this fragment three
      identically oriented and closely spaced open reading frames (ORFs) were
      identified and designated bfpT, bfpV and bfpW. bfpT is predicted to encode a 31.8
      kDa protein that shares homology with the AraC family of transcriptional
      regulators, including the presence of a conserved C-terminal DNA-binding helix
      turn-helix motif. Insertional inactivation of bfpT led to the loss of bfpA
      transcription, BfpA protein production and the localized adherence (LA)
      phenotype; this mutant phenotype could be complemented by introduction of bfpTVW
      and, on separate plasmids, bfpT + bfpW. However, introduction of bfpT + bfpV,
      bfpV alone, bfpW alone, or bfpV + bfpW did not enable recovery of the wild-type
      phenotype. Maximal efficiency of bfpA transcription required all three genes, but
      bfpV and bfpW each enhanced transcription providing bfpT was also present. A
      series of deletions of the bfpA upstream promoter region was prepared; with
      respect to the bfpA transcription start site, sequence between nucleotides -94
      and -55 was found to bind bfpT. BfpT also bound a DNA fragment containing the
      eaeA promoter region on the EPEC chromosome. From these results we conclude that
      bfpTV W causes transcriptional activation of bfpA, and possibly eaeA, by a trans
      acting mechanism that may co-ordinately regulate the expression of EPEC virulence
      determinants.

PMID- 8885269
TI  - Replacement of the lysine residue in the consensus ATP-binding sequence of the
      AddA subunit of AddAB drastically affects chromosomal recombination in
      transformation and transduction of Bacillus subtilis.
AB  - The ATP-dependent deoxyribonuclease enzyme complex (AddAB) of Bacillus subtilis
      possesses two consensus ATP-binding sequences, located in the N-terminal region
      of both subunits. The highly conserved lysine residues in both consensus ATP
      binding sequences were replaced by glycine, resulting in the mutant enzyme
      complexes AddAB-A-K36G (AddA*B) and AddAB-B-K14G (AddAB*). The mutation in
      subunit AddA reduced DNA repair and chromosomal transformation, and abolished
      bacteriophage PBS1-mediated transduction. This mutation also resulted in a
      complete loss of the ATP-dependent exonuclease and helicase activity. In
      contrast, the mutation in subunit AddB had only marginal effects. The recF and
      addAB genes are not required for transformation with plasmid DNA, but have
      overlapping activities in transformation with chromosomal DNA. By contrast to
      RecF, the AddAB enzyme is essential for PBS1-mediated transduction. However, recF
      has a more important function with respect to DNA repair than addAB.

PMID- 8885268
TI  - Identification of a ClpC ATPase required for stress tolerance and in vivo
      survival of Listeria monocytogenes.
AB  - We identified a new chromosomal locus involved in the virulence of the
      facultative intracellular pathogen Listeria monocytogenes. This locus displays
      the same genetic organization as that of the clpC/mecB locus of Bacillus
      subtilis. It contains a thermoregulated operon of four genes, whose transcription
      is upregulated at 42 degrees C. The last gene of this operon is clpC, which
      encodes a protein of 826 amino acid residues, identified as a ClpC ATPase,
      sharing a strong peptide sequence identity (78%) with ClpC/MecB of B. subtilis.
      Tn917 insertions inactivating the entire operon, or only clpC, gave mutants
      highly susceptible to stress, including iron limitation, elevated temperatures
      and high osmolarity. The virulence of these mutants was severely impaired in the
      mouse. A clpC insertional mutant was also restricted in its capacity to grow in
      bone-marrow-derived macrophages. These results demonstrate that the ClpC ATPase
      of L. monocytogenes is a general stress protein involved in intracellular growth
      and in vivo survival of this pathogen in host tissues.

PMID- 8885270
TI  - Ferric uptake regulator mutants of Pseudomonas aeruginosa with distinct
      alterations in the iron-dependent repression of exotoxin A and siderophores in
      aerobic and microaerobic environments.
AB  - Because the ferric uptake regulator (fur) appears to be an essential gene in
      Pseudomonas aeruginosa, resistance to manganese was used as an enrichment to
      isolate strains carrying point mutations in the fur gene in order to assess its
      role in the co-ordinate expression of siderophores and exotoxin A (ETA). This
      report describes a detailed molecular and phenotypic characterization of four
      mutants and one revertant, which carry point mutations in the fur gene. Two
      parental strains were used in this study. Three mutants were isolated from the
      widely used strain, PAO1. One of these, CS (cold sensitive), has a mutation in
      the 5' non-coding region of the fur gene while the two other mutants derived from
      this parent have mutations resulting in the following deduced changes in Fur:
      mutant A2, H86-->R; mutant A4, H86-->Y. The other mutant (C6) and its revertant
      (C6Rv) were derived from PAO6261, a mutant of PAO1 with a deletion in the anr
      gene (anaerobic regulation of arginine deiminase and nitrate reduction) that
      controls anaerobic respiration in P. aeruginosa. Fur from the C6 mutant has an
      A10-->G mutation while in the C6Rv spontaneous revertant the mutant Gly residue
      has been changed to Ser at this position. All mutants were examined for
      alterations in the iron-regulated expression of siderophores and ETA. The A2 and
      A4 mutants expressed higher levels of siderophores in iron-deficient media and in
      iron-replete media. The CS mutant constitutively expressed siderophores at 25
      degrees C. At 42 degrees C siderophore biosynthesis was iron repressed as in the
      parental strain PAO1. The deletion of anr in PAO6261 had no apparent effect on
      the iron-mediated regulation of siderophore synthesis, but the C6 mutant derived
      from this strain produces siderophores constitutively. The iron-regulated
      production of siderophores by C6Rv was similar to the parental strain PAO6261 and
      PAO1. Because one of the parental strains used in this study is an Anr mutant,
      regulation of ETA production was assessed under aerobic and microaerobic
      conditions. Iron-dependent repression of ETA synthesis in both parental strains
      and A2 and A4 mutants was found to be 50-100-fold under aerobic and microaerobic
      conditions, as assayed by quantitative Western dot-blot assays. By contrast in
      the CS and C6 mutants, while iron-dependent repression os ETA synthesis was
      similar to both parental strains under aerobic conditions, ETA production in
      these mutants was constitutive in a microaerobic environment. RNase protection
      analysis of toxA and regAB transcription in PAO1, PAO6261 and the C6 mutant
      corroborated the results of quantitative dot-blot assays of ETA. The mutant Fur
      proteins were purified and examined for their ability to bind to the promoter of
      a gene (pvdS) that positively regulates the expression of siderophores and ETA.
      Fur from the A2 and A4 mutants and from the C6Rv revertant was able to bind to
      the target DNA, but with reduced affinity by comparison to wild-type Fur. Fur
      from the C6 mutant in DNase I footprint experiments failed to protect the
      promoter region of the pvdS gene, but it retained some weak binding activity in
      gel mobility shift assays. The data presented in this study not only furnish some
      additional insights into the structure-function relationships of Fur, but also
      afford novel perspectives of virulence factors in P. aeruginosa under
      environmental conditions that have not previously been considered.

PMID- 8885271
TI  - Exotoxin A production in Pseudomonas aeruginosa requires the iron-regulated pvdS
      gene encoding an alternative sigma factor.
AB  - Exotoxin A (ETA) is secreted by Pseudomonas aeruginosa under iron-limiting growth
      conditions. The ETA structural gene, toxA, is regulated at the transcriptional
      level by the gene products of the regAB operon. The expression of both toxA and
      regAB is repressed under iron-replete conditions, suggesting a role for the
      ferric uptake regulator (Fur) in regulation of ETA synthesis; however, the Fur
      protein does not interact directly with the toxA or the regAB promoters. Evidence
      is presented that the iron control of ETA synthesis is mediated by a Fur
      regulated alternative sigma factor, PvdS, which had initially been identified as
      a positive activator for the production of the siderophore pyoverdin. In a delta
      pvdS deletion mutant, ETA was produced at low levels of less than 5% compared to
      wild type, but still in response to iron starvation, and introduction of a
      functional pvdS gene on a plasmid fully restored wild-type levels and normal iron
      regulation of ETA synthesis. Therefore, a functional pvdS locus is essential for
      ETA production. Neither toxA nor regAB mRNA was detectable in a delta pvdS
      mutant. Overexpression of pvdS from the tac promoter on a plasmid resulted in a
      high-level and iron-independent production of ETA in wild-type PAO1, in the delta
      pvdS strain, but not in a delta regA strain as a host. These findings suggest
      that PvdS is required for the activation of the regAB promoters. The
      transcription of regAB and toxA after induction of the P tac-pvdS gene was
      monitored in cells grown in high-iron medium. While both regAB and toxA were
      highly expressed during all growth phases under microaerobic conditions, toxA
      transcripts were detected only during the exponential but not the early
      stationary phase of growth under aerobic conditions. These results suggest that a
      second regulatory mechanism besides the Fur-PvdS system is involved in iron
      regulation of ETA production.

PMID- 8885272
TI  - The P1 ParA protein and its ATPase activity play a direct role in the segregation
      of plasmid copies to daughter cells.
AB  - The P1 ParA protein is an ATPase that recognizes the parA promoter region where
      it acts to autoregulate the P1 parA-parB operon. The ParB protein is essential
      for plasmid partition and recognizes the cis-acting partition site parS. The
      regulatory role of ParA is also essential because a controlled level of ParB
      protein is critical for partition. However, we show that this regulatory activity
      is not the only role for ParA in partition. Efficient partition can be achieved
      without autoregulation as long as Par protein levels are kept within a range of
      low values. The properties of ParA mutants in these conditions showed that ParA
      is essential for some critical step in the partition process that is independent
      of par operon regulation. The putative nucleotide-binding site for the ParA
      ATPase was identified and disrupted by mutation. The resulting mutant was
      substantially defective for autoregulation and completely inactive for partition
      in a system in which the need for autoregulation is abolished. Thus, the ParA
      nucleotide-binding site appears to be necessary both for the repressor activity
      of ParA and for some essential step in the partition process itself. We propose
      that the nucleotide-bound form of the enzyme adopts a configuration that favours
      binding to the operator, but that the ATPase activity of ParA is required for
      some energetic step in partition of the plasmid copies to daughter cells.

PMID- 8885273
TI  - Nucleotide sequence and role in DNA amplification of the direct repeats composing
      the amplifiable element AUD1 of Streptomyces lividans 66.
AB  - The amplifiable unit of DNA no. 1 (AUD1) of Streptomyces lividans consists of
      three 1 kb repeats (left direct repeat, LDR; middle direct repeat, MDR; and the
      slightly different right direct repeat, RDR) and two 4.7 kb repeats alternately
      arranged in identical orientation to each other. Both 4.7 kb repeats have been
      sequenced. They are identical and contain one open reading frame (orf4.7). The
      deduced amino acid sequence has a low similarity to chitinases, and two amino
      acid repeats present high similarities to fibronectin type III modules.
      Sequencing had previously shown that the ORF corresponding to each 1 kb repeat
      encodes a putative DNA-binding protein. Crude extracts of Escherichia coli
      overexpressing the orfRDR-encoded protein and of S. lividans Jni1, having a high
      amplification of AUD1 and therefore orfMDR, were used in gel retardation assays.
      The orfRDR- and probably the orfMDR-encoded proteins can bind to an imperfect
      palindromic sequence upstream from MDR and RDR and to another sequence downstream
      from RDR. An extrachromosomal DNA amplification system was constructed containing
      different combinations of the sequences composing AUD1. In mutants having a
      deletion of the chromosomal AUD1, the 4.7 kb repeats could be reduced in size,
      mutated or replaced by E. coli DNA without altering the ability to amplify when
      RDR was present. Therefore, the only function of the 4.7 kb repeats in
      amplification is to provide directly repeated DNA sequences. When RDR was lacking
      or mutated, no amplification was observed. This strongly suggests that the DNA
      binding protein encoded by orfRDR is required for AUD1 amplification.

PMID- 8885274
TI  - Programmed cell death in bacteria: translational repression by mRNA end-pairing.
AB  - The hok/sok and pnd systems of plasmids R1 and R483 mediate plasmid maintenance
      by killing plasmid-free cells. Translation of the exceptionally stable hok and
      pnd mRNAs is repressed by unstable antisense RNAs. The different stabilities of
      the killer mRNAs and their cognate repressors explain the onset of translation in
      plasmid-free cells. The full-length hok and pnd mRNAs are inert with respect to
      translation and antisense RNA binding. We have previously shown that the mRNAs
      contain two negative translational control elements. Thus, the mRNAs contain
      upstream anti-Shine-Dalgarno elements that repress translation by shielding the
      Shine-Dalgarno elements. The mRNAs also contain fold-back-inhibition elements
      (fbi) at their 3' ends that are required to maintain the inert mRNA
      configuration. Using genetic complementation, we show that the 3' fbi elements
      pair with the very 5' ends of the mRNAs. This pairing sets the low rate of 3'
      exonucleolytical processing, which is required for the accumulation of an
      activatable pool of mRNA. Unexpectedly, the hok and pnd mRNAs were found to
      contain translational activators at their 5' ends (termed tac). Thus, the fbi
      elements inhibit translation of the full-length mRNAs by sequestration of the tac
      elements. The fbi elements are removed by 3' exonucleolytical processing.
      Mutational analyses indicate that the 3' processing triggers refolding of the
      mRNA 5' ends into translatable configurations in which the 5' tac elements base
      pair with the anti-Shine-Dalgarno sequences.

PMID- 8885275
TI  - Membrane topology of the yeast uracil permease.
AB  - The uracil permease of Saccharomyces cerevisiae is a 633 residue polytopic plasma
      membrane protein. Hydropathy profile analysis indicates that this protein has
      long hydrophilic N- and C-termini and 10-12 potential transmembrane segments.
      Previous results based on analysis of hybrid proteins allowed identification of
      the first transmembrane segment of uracil permease, and provided a preliminary
      indication of the cytoplasmic orientation of its N-terminus. In this work, other
      experimental approaches were used to confirm this orientation, and to determine
      that of the C-terminus. Epitopes in the N- and the C-termini of the protein were
      protected against trypsin degradation on intact protoplasts, but readily digested
      on permeabilized protoplasts. Immunofluorescent analysis showed that antibodies
      to the last 10 amino acids of uracil permease bind to detergent-treated
      protoplasts, but not to intact ones. Carboxypeptidase digested the C-terminus of
      uracil permease inserted into the sealed dog-pancreas microsomes. These results
      establish that both N- and C-termini are cytoplasmic, the permease polypeptide
      spanning the membrane an even number of times. The orientation of several
      hydrophilic loops with respect to the membrane was investigated by introducing
      potential glycosylation sites into these regions. We checked whether the
      resulting mutant proteins were glycosylated when expressed in the presence of dog
      pancreas microsomes. Our data show that two loops of the protein are lumenal.
      Together with previous results, this work indicates that uracil permease is a 10
      membrane-spanning protein, with rather small external loops and three main
      cytoplasmic regions (the N- and C-termini and a central 60-residue loop).

PMID- 8885276
TI  - The cutRS signal transduction system of Streptomyces lividans represses the
      biosynthesis of the polyketide antibiotic actinorhodin.
AB  - The nucleotide sequence of a two-component signal transduction operon (cutRS) of
      Streptomyces lividans TK64 was elucidated. Transcription of the operon was
      detected during the transition and stationary phases of growth, initiating at a
      single site upstream of cutR. This promoter region also possessed promoter
      activity directed away from cutRS, which appears to be responsible for the
      previously observed suppression of the translational deficiency of a melC1
      mutation. Mutations in cutR and cutS were generated by gene replacement. The
      resulting mutants exhibited accelerated and increased production of the
      polyketide antibiotic, actinorhodin, which could be reversed by introduction of
      cutR on a plasmid. cutRS was also shown to repress actinorhodin production in the
      closely related species, Streptomyces coelicolor A3(2). The cutRS operon is the
      second two-component system found in Streptomyces that negatively regulates
      secondary metabolism.

PMID- 8885277
TI  - Molecular characterization of group A streptococcal (GAS) oligopeptide permease
      (opp) and its effect on cysteine protease production.
AB  - Bacterial oligopeptide permeases are membrane-associated complexes of five
      proteins belonging to the ABC-transporter family, which have been found to be
      involved in obtaining nutrients, cell-wall metabolism, competence, and adherence
      to host cells. A lambda library of the strain CS101 group A streptococcal (GAS)
      genome was used to sequence 10,192 bp containing the five genes oppA to oppF of
      the GAS opp operon. The deduced amino acid sequences exhibited 50-84% homology to
      pneumococcal AmiA to AmiF sequences. The operon organization of the five genes
      was confirmed by transcriptional analysis and an additional shorter oppA
      transcript was detected. Insertional inactivation was used to create serotype M49
      strains which did not express either the oppA gene or the ATPase genes, oppD and
      oppF. The mutation in oppA confirmed that the additional shorter oppA transcript
      originated from the opp operon and was probably due to an intra-operon
      transcription terminator site located downstream of oppA. While growth kinetics,
      binding of serum proteins, and attachment to eukaryotic cells were unaffected,
      the oppD/F mutants showed reduced production of the cysteine protease, SpeB, and
      a change in the pattern of secreted proteins. Thus, the GAS opp operon appears to
      contribute to both protease production and export/processing of secreted
      proteins.

PMID- 8885278
TI  - Salmonella spp. are cytotoxic for cultured macrophages.
AB  - We have shown by a variety of microscopical and biochemical techniques that
      Salmonella spp. are cytotoxic for cultured J774A.1 and bone marrow-derived murine
      macrophages. The cytotoxicity is initially manifested by inhibition of membrane
      ruffling and macropinocytosis in infected macrophages, and is followed by cell
      death. Macrophages killed by Salmonella spp. exhibited features of apoptosis such
      as condensation and fragmentation of chromatin, membrane blebbing, and the
      presence of cytoplasmic nucleosomes and apoptotic bodies. Cytotoxicity does not
      require bacterial internalization as cytochalasin D, a drug that prevents
      bacterial uptake, did not prevent Salmonella-induced macrophage cell death.
      However, the cytotoxic effects are strictly dependent upon the expression of the
      invasion-associated Type III protein-secretion system encoded at centisome 63 of
      the Salmonella chromosome. Wild-type Salmonella typhimurium grown under
      conditions that do not allow optical expression of this system or strains of
      Salmonella carrying mutations in genes that encode components of this protein
      secretion system were devoid of macrophage cytotoxicity. In addition, mutations
      in invJ, spaO, sipB, sipC and sipD, which encode proteins that are secreted via
      this secretion apparatus and are required for bacterial entry into non-phagocytic
      cells, also abolished the toxicity. In contrast, mutations in sipA and sptP,
      which encode secreted proteins that are not required for bacterial invasion, had
      no effect on macrophage cytotoxicity. These results indicate a close correlation
      between the mechanisms of bacterial internalization into non-phagocytic cells and
      those that lead to macrophage cytotoxicity. Host-adapted serotypes of Salmonella
      such as S. typhi, S. gallinarum and S. dublin were also toxic for murine
      macrophages, indicating that this virulence property is probably present in most
      Salmonella spp. and is not associated with the mechanisms responsible for host
      range.

PMID- 8885279
TI  - Nitric oxide precursor arginine and S-nitrosoglutathione in synaptic and glial
      function.
AB  - In the last few years, there has been an important increase in interest in nitric
      oxide (NO) as an intercellular messenger, and its putative role in numerous CNS
      functions is being continually updated. Arginine, the nitric oxide precursor, has
      been found in our laboratory to be released following stimulation of the white
      matter in the cerebellum and of sensory afferents in the thalamus. Since arginine
      is localized in glial cells while the nitric oxide synthesizing enzyme is
      localized in different cells (predominantly in neurons), these findings may
      represent a transfer of arginine from glia to neurons in order to supply the
      nitric oxide synthase with its substrate. The mechanism underlying this glial
      neuronal interaction seems to involve the activation of excitatory amino acid
      receptors present on glial cells. Our results speak for an intense crosstalk
      between neurons and glia (activation of glial receptors by neurotransmitter
      released from neurons) and between glia and neurons (supply of the nitric
      precursor arginine from glia to neurons). The form in which NO is released from
      cells has been much debated. The chemical identity of the endothelial-derived
      relaxing factor in particular is still a matter of dispute, the major contender
      being NO. and a S-nitrosothiol compound. Based on the strong reactivity of NO for
      thiols and on the presence of cysteine and glutathione at the mM level
      intracellularly and microM level extracellularly, we have investigated whether S
      nitrosothiols, i.e. S-nitrosoglutathione, may be the potential "package" form in
      which NO could be stored. We demonstrated, with HPLC coupled to mass spectrometry
      techniques, the presence of endogenous nitrosoglutathione in rat brain tissue.
      This packaging of NO in the form of nitrosothiols might serve to facilitate its
      transfer, prolong its life, and target its delivery to specific effectors. That
      could confer a specificity of action to the widely diffusable messenger NO, may
      determine the range of effectiveness of NO and mitigate its adverse cytotoxic
      effects.

PMID- 8885280
TI  - The dawn of excitatory amino acid research in Japan. The pioneering work by
      Professor Takashi Hayashi.
AB  - The excitatory action of glutamate and aspartate upon direct application to the
      motor cortex of dogs was first reported in 1952 by Takashi Hayashi, Keio
      University School of Medicine, Tokyo. Although this investigation had been
      performed in the early 1940s during the Second World War, the publication in
      English was delayed in the difficult post-war circumstances. When sodium
      glutamate was applied to the exposed motor cortex in 1-2 mol (not mmol)
      concentrations, the convulsions of a clonic type were produced with very short
      latent periods. He injected glutamate free-hand by using an intradermic syringe
      for humans. Stimulation by glutamate was solely effective in the grey matter. If
      entered into the white matter, it had no motor effects. When Hayashi undertook
      this investigation, glutamate was not known to exist in a high concentration in
      the brain. Hayashi proposed the physiological role of glutamate in the brain
      excitation, and hypothesized that glutamate might be inactive in the brain
      tissue, probably bound to protein, and that upon release from protein the
      excitatory action might be expressed. The electrical stimulation of the cortex
      was suggested to induce the release of glutamate from protein.

PMID- 8885281
TI  - Glutamatergic regulation of [3H]acetylcholine release in striatal slices of
      normotensive and spontaneously hypertensive rats.
AB  - It has been proposed that central cholinergic neurons may actively participate in
      blood pressure control and other cardiovascular regulations. The present study
      was performed to investigate the role of the glutamate receptors in the
      regulation of acetylcholine release in rat central nervous system in vitro. In
      the Mg2+-free condition, L-glutamate, an endogenous ligand for glutamate
      receptors, elicited [3H]acetylcholine release from striatal slices of Sprague
      Dawley rats in a dose-related fashion. Glycine, an allosteric agonist for the N
      methyl-D-aspartate type of glutamate receptor, significantly potentiated the
      increase in [3H]acetylcholine release evoked by L-glutamate. A non-competitive N
      methyl-D-aspartate receptor antagonist, MK-801, blocked the L-glutamate-induced
      increase in [3H]acetylcholine release, although MK-801 had no effects on its own.
      In spontaneously hypertensive rats, the facilitatory effect of L-glutamate on
      [3H]acetylcholine release was significantly smaller than that in Wistar-Kyoto
      rats. Moreover, L-glutamate in combination with glycine increased the release of
      [3H]acetylcholine to a lesser extent in SHR than in WKY rats. These results show
      that L-glutamate increased acetylcholine release from rat striatum, which was
      highly dependent on the N-methyl-D-aspartate type of glutamate receptor.
      Furthermore, the lesser facilitation of acetylcholine release by L-glutamate in
      spontaneously hypertensive rats suggests that the excitatory amino acid may be,
      at least in part, involved in the regulation of central cholinergic nerve
      activity in hypertension.

PMID- 8885282
TI  - A postmortem study of glycine and its potential precursors in chronic
      schizophrenics.
AB  - We have measured the concentrations of glycine and its potential precursors,
      serine and threonine, in 20 areas of the postmortem brains of chronic
      schizophrenics and controls using high-performance liquid chromatography by pre
      column derivatization with dimethyl-amino-azobenzene sulphonyl chloride. The
      regional distribution pattern of glycine in the postmortem brains with and
      without the disease was more similar to that of serine (r = 0.874, P < 0.0001)
      than to that of threonine (r = 0.476, P < 0.01). A multiple regression analysis
      with regressor variables including diagnosis, age at death and interval between
      death and freezing revealed that there is a significant difference between
      schizophrenics and controls in the contents of these amino acids in a number of
      brain areas. The level of glycine in the orbitofrontal cortex of schizophrenics
      was found to be significantly increased in schizophrenics, with a tendency to an
      increase in that of serine. The increase in glycine was also significantly high
      in the off-drug group of schizophrenics who had not taken antipsychotics more
      than 40 days before death. Prominent decreases in both glycine and serine were
      observed in the somesthetic cortex of the on-drug schizophrenics. Serine was
      found to be significantly decreased in the putamen of the off-drug
      schizophrenics. A marked decrease in threonine was also observed in the
      supramarginal cortex and posterior portion of the lateral occipitotemporal cortex
      of the off-drug group of schizophrenics and in the putamen of all schizophrenics.
      The highly similar distribution pattern of glycine and serine in the postmortem
      brains supports the close coupling of synthesis and metabolism between these
      chemicals in human brains. The increased content of glycine in the orbitofrontal
      cortex, the reduced level of serine in the putamen and the decrease in threonine
      in the cerebral cortices, which were prominent in the off-drug schizophrenics,
      may be involved in the pathophysiology of schizophrenia.

PMID- 8885283
TI  - Temporal and spatial differences in intracellular Ca++ changes elicited by K+ and
      glutamate in single cultured neocortical neurons.
AB  - Changes as a function of time in the intracellular Ca++ concentration ([Ca++]i)
      in cultured cerebral cortical neurons were monitored after exposure of the cells
      to either 55 mM KCl or 100 microM glutamate using the fluorescent Ca++ chelator
      fura-2. The changes in [Ca++]i were followed in both cell bodies and neurites.
      Depolarization with K+ led to an immediate increase in [Ca++]i in neurites
      followed by a slower rise in the cell bodies. In contrast, glutamate elicited a
      slow increase in [Ca++]i in both neurites and cell bodies, and this increase
      showed a plateau rather than a peak as that seen after exposure to K+. The Ca++
      channel blockers verapamil and nifedipine affecting N- and L-type channels,
      respectively had differential effects on K+ stimulated increases in [Ca++]i.
      Nifedipine only affected the increase marginally whereas verapamil inhibited the
      response by 50-60% both in cell bodies and neurites. The glutamate-induced
      increase in [Ca++]i was inhibited by nifedipine by 60% in neurites whereas no
      effect was observed in cell bodies. The results show that depolarization elicited
      by K+ and glutamate has different effects in different parts of the neurons and
      that the pharmacological characteristics of voltage gated Ca++ channels are
      dramatically different in cell bodies and neurites. Moreover, the distribution of
      L-type channels activated by glutamate differs in cell bodies and neurites. Such
      differences in the spatial distribution of Ca++ channels are likely to be of
      major importance for the functional consequences of depolarization coupled
      increases in [Ca++]i such as transmitter release and neurotoxicity.

PMID- 8885284
TI  - Studies of NMDA- and non-NMDA-mediated neurotoxicity in cultured neurons.
AB  - The neurotoxic effects of various glutamate agonists were studied using whole
      fetal rat brain cultures. The results showed that L-glutamate (L-glu) and N
      methyl-D-aspartate (NMDA) were the most potent agonists for inducing
      neurotoxicity, producing significant toxicity at 0.10 and 0.01 mM concentrations,
      respectively. Kainic acid (KA) and quisqualic acid (QA) also produced
      neurotoxicity, but only at a relatively high concentration (1.0 mM). No other
      glutamate agonist tested produced neurotoxicity in the cultures following brief
      incubations. The effects of each agonist were found to be Ca2+ dependent, and the
      selective NMDA Ca2+ channel agonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,1 0-imine hydrogen maleate (MK-801), blocked the
      toxicity produced by all the glutamate agonists. Thus, the results of this study
      found little or no evidence for a direct non-NMDA receptor mediated
      neurotoxicity. These results suggest that the neurotoxicity produced by the non
      NMDA agonists may be due to one of the following mechanisms: (i) non-specific
      binding of non-NMDA agonists to NMDA receptor; (ii) release of L-glu via non-NMDA
      agonists induced depolarization of cell membrane and subsequent activation of
      NMDA receptor by released L-glu; (iii) inhibition of L-glu uptake by non-NMDA
      agonists resulting in activation of L-glu receptors including NMDA receptors.

PMID- 8885285
TI  - Antigens associated with specific retinal cells are affected by ischaemia caused
      by raised intraocular pressure: effect of glutamate antagonists.
AB  - Raising the rat's intraocular pressure above the systolic blood pressure for 60
      min followed by a reperfusion of 7-10 days caused an ischaemic insult to the
      retina. The b-wave of the electroretinogram was abolished and the retinal
      thickness was much reduced, the greatest influence being associated with the
      inner retinal layers. No obvious histological damage was apparent at the light
      microscopy level. Immunocytochemistry, however, revealed a clear change in the
      nature of certain antigens associated with specific cell-types. Thy-1 antigen
      located to ganglion cell membranes was much reduced, suggesting that the ganglion
      cells are affected by ischaemia. Calretinin-immunoreactivity associated with
      amacrine cells is drastically reduced by ischaemia. In contrast, Ret-P1, located
      to the outer segments of the photoreceptors is unaffected by ischaemia. Ischaemia
      also caused GFAP-immunoreactivity to be expressed in the Muller cells, which is
      normally only associated with astrocytes in the ganglion/nerve fibre layer.
      Injection of a mixture of CNQX and MK-801, kainate and NMDA receptor antagonists,
      respectively, into the eye just before ischaemia failed to reverse the changes
      induced by the insult. However, analysis 3 days after reperfusion revealed that
      when the ischaemic insult was reduced to 45, rather than 60 min, the changes in
      the calretinin-immunoreactivity were reversed. The results show that
      immunocytochemistry provides a powerful way of following biochemical changes
      associated with specific cell types caused by ischaemia.

PMID- 8885286
TI  - Involvement of nitric oxide in spinally mediated capsaicin- and glutamate-induced
      behavioural responses in the mouse.
AB  - The intrathecal (i.t.) injection of capsaicin (0.1 nmol/mouse) through a lumbar
      puncture elicited scratching, biting and licking responses. Pretreatment with the
      nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (320
      nmol), by i.t. injection, resulted in a significant inhibition of the behavioural
      response produced by i.t. capsaicin (0.1 nmol/mouse). Similar behavioural
      responses were induced by i.t. injections of NMDA (0.4 nmol), kainate (0.05 nmol)
      or AMPA (0.05 nmol), which were all inhibited by co-administration of L-NAME (20
      80 nmol). L-Arginine (600 mg/kg, i.p.) but not D-arginine (600 mg/kg, i.p.)
      reversed the inhibitory effect of L-NAME on capsaicin-, NMDA-, kainate- and AMPA
      induced behavioural response. Scratching, biting and licking responses induced by
      tachykinin receptor agonists, substance P, [Sar9,Met(O2)11]substance P,
      neurokinin A and neurokinin B were not affected by co-administration of L-NAME
      (40 and 80 nmol). These results suggest that spinal nitric oxide may play a
      significant role in mechanisms of the behavioural response to capsaicin, probably
      through the release of glutamate, but not tachykinins.

PMID- 8885287
TI  - The effects of single and repeated phencyclidine administration on [125I]
      iomazenil binding in the rat brain.
AB  - We measured [125I] iomazenil binding, labeling the central-type benzodiazepine
      receptor in 37 discrete rat brain areas following single (7.5 mg/kg, i.p.) and
      repeated (7.5 mg/kg/day x 14 days, i.p.) treatment with phencyclidine (PCP), a
      non-competitive antagonist of the N-methyl-D-aspartate(NMDA)-type glutamate
      receptor, using in vitro quantitative autoradiographic receptor binding assay.
      Both single and repeated PCP treatment produced heterogeneous changes in the rat
      brain in a similar manner, the magnitude of change in [125I] iomazenil binding
      being generally greater in the repeated treatment group than in the single
      treatment group. A significant increase in [125I] iomazenil binding was observed
      in the superficial layer (layer I-IV) of the parietal cortex in both of the PCP
      treatment groups and the CA1 of the hippocampus of the repeated PCP-treated
      group. There was a significant decrease in [125I] iomazenil binding in the
      piriform cortex of the repeated PCP-treated group. These results suggest that the
      blockade of NMDA receptor-mediated glutamatergic neurotransmission by PCP
      produces the compensational alterations in the central-type benzodiazepine
      receptor antagonist binding, and that the observed diversity may be due to
      dissimilar modes of organizations between glutamatergic and the GABA(gamma
      aminobutyric acid)-benzodiazepine receptor complex.

PMID- 8885288
TI  - Particular nuclear transcription factors responsive to systemic administration of
      kainic acid in murine brain.
AB  - Gel retardation electrophoresis revealed that binding of a radiolabeled double
      stranded oligonucleotide probe for the nuclear transcription factor activator
      protein-1 (AP1) was markedly potentiated 2 h after the intraperitoneal injection
      of kainic acid (KA) at a dose range of 10-40 mg/kg in a dose-dependent manner in
      the murine hippocampus. The potentiation was seen in a manner independent of the
      crisis of convulsive seizures following the administration of KA at different
      doses. At the highest dose employed, the systemic KA significantly potentiated
      the AP1 binding in most central discrete structures examined except the
      cerebellum. In contrast, KA significantly potentiated binding of a radiolabeled
      probe for cyclic AMP response element binding protein (CREB) in a dose-dependent
      fashion in the hippocampus, without altering that in other parts of murine brain.
      No significant alteration was detected in binding of a probe for c-Myc in any
      brain regions examined 2 h after the administration of KA at different doses.
      However, immunoblotting analysis demonstrated that KA was ineffective in altering
      endogenous levels of both CREB and CREB phosphorylated at serine133 in the
      hippocampus and cerebellum. These results suggest that in vivo systemic KA
      signals may be selectively transduced to nuclear AP1 in the hippocampus through a
      mechanism different from phosphorylation of CREB at serine133 in murine brain.

PMID- 8885289
TI  - The role of glutamate in behavioral and neurotoxic effects of methamphetamine.
AB  - Studies on the mechanisms of behavioral and neurochemical effects of amphetamine
      or methamphetamine (MA) have focused on the dopaminergic system. However, recent
      reports suggest that the glutamatergic system may be involved in the MA effects.
      Our laboratory has been conducting a series of experiments to further examine the
      role of glutamate in both behavioral and neurotoxic effects of MA. These studies
      include (1) behavioral studies on the effect of N-methyl-D-aspartate (NMDA)
      antagonists on the development of MA-induced behavioral sensitization, (2)
      neurochemical studies on the effects of NMDA antagonists on MA-induced
      neurotoxicity, and (3) in vivo microdialysis studies on the effects of MA on
      glutamate release. In the present paper, the authors comment on an important role
      of glutamatergic systems in the behavioral and toxic effects of MA.

PMID- 8885290
TI  - Functional partial agonism at ionotropic excitatory amino acid receptors.
AB  - (RS)-2-Amino-3-(3-hydroxy-5-phenyl-4-isoxazolyl)propionic acid (APPA), which is
      an analogue of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid
      (AMPA), shows the characteristics of a partial AMPA receptor agonist. Since (S)
      APPA is a full AMPA agonist and (R)-APPA a competitive antagonist, the partial
      agonism observed for APPA, which is a 1:1 mixture of (S)- and (R)-APPA, is only
      apparent. These observations have prompted comparative pharmacological studies of
      different molar ratios of a series of AMPA and N-methyl-D-aspartic acid (NMDA)
      agonists and respective competitive antagonists, and of these agonists in the
      presence of fixed concentrations of antagonist. Using the rat cortical wedge
      preparation, the latter series of experiments showed the expected rightward
      parallel shifts of the dose-response curves. The former type of experiments, on
      the other hand, produced dose-response curves at different levels of maximal
      response, depending on the molar ratios of agonist and antagonist used. This
      phenomenon, which is in agreement with the theory for competitive receptor
      interaction, has been termed functional partial agonism, a new pharmacological
      concept of potential therapeutic utility. These results were obtained using AMPA,
      the AMPA agonist (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic
      acid (ATPA), the competitive AMPA antagonists (RS)-2-amino-3-(3-carboxymethoxy-5
      methyl-4-isoxazolyl)propionic acid (AMOA) and 6-nitro-7-sulfamoylbenzo[f]
      quinoxalin-2,3-dione (NBQX), NMDA, and the competitive NMDA antagonist (RS)-3-(2
      carboxy-4-piperazinyl)propyl-1-phosphonic acid (CPP).

PMID- 8885291
TI  - Characterization of the metabotropic glutamate receptors (mGluRs) which modulate
      GABA-mediated inhibition in the ventrobasal thalamus.
AB  - The ventrobasal thalamus (VB) relays and processes somatosensory information
      ascending to the cerebral cortex. Several types of mGluR are known to be present
      in VB, and we have previously shown that Group II and Group III mGluR agonists
      can reduce inhibitory synaptic transmission by acting at presynaptic receptors on
      GABAergic terminals in this structure. We have tested the action of several
      antagonists against the disinhibitory action of the Group II agonist CCG-I
      [(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine] and the Group III agonist L-AP4
      [L-2-amino-4-phosphonobutyrate] in the VB of anaesthetized rats using
      extracellular single-neurone recording techniques and iontophoretic applications
      of mGluR antagonists and agonists. The antagonists MAP4 [alpha-methyl-L-AP4] and
      MPPG [(+/-)-alpha-methyl-4-phosphonophenylglycine] reduced the disinhibitory
      actions of L-AP4 whilst having little effect on the disinhibitory action of CCG
      I. In contrast, MCCG [alpha-methyl-CCG-I] and MCPG [(+)-alpha-methyl-4
      carboxyphenylglycine] antagonized CCG-I, whilst having less effect against L-AP4
      responses. These results support the hypothesis that GABAergic inhibitory
      transmission in VB can be modulated by at least two types of mGluR, belonging to
      Group II and Group III. Furthermore, the novel antagonists appear to be useful
      tools for the future study of the physiological role of these receptors in
      thalamic sensory processing.

PMID- 8885293
TI  - Pharmaceuticals ... too much of a good thing.

PMID- 8885292
TI  - Binding of double stranded oligonucleotide probes for particular transcription
      factors with leucine-zipper motifs in discrete brain structures of mice with
      acquired and inherent spontaneous seizures.
AB  - Nuclear extracts of mouse brain contained binding of radiolabeled oligonucleotide
      probes for particular transcription factors with leucine-zipper motifs including
      activator protein-1 (AP1), cyclic AMP response element binding protein (CREB) and
      c-Myc. An acute intraperitoneal injection of pentylenetetrazole (PTZ) at a
      convulsive dose significantly potentiated binding of the probe for AP1 in the
      cerebral cortex, hippocampus, striatum, hypothalamus and midbrain, without
      affecting that in the medulla-pons and cerebellum, 2 h after the administration.
      However, PTZ failed to affect binding of the probe for CREB under the similar
      experimental conditions. In contrast, PTZ induced a slight but statistically
      significant decrease in binding of the AP1 probe in the cerebellum, without
      altering that in the hippocampus, 14 h after the injection. On the other hand,
      repeated administration of PTZ at a subconvulsive dose led to spontaneous
      kindling seizures in animals, with a concomitant decrease in binding of the AP1
      probe in both the hippocampus and cerebellum. In contrast to these animals with
      acquired spontaneous seizures, however, binding of the AP1 probe was
      significantly higher in three different telencephalic structures of inherently
      spontaneous epileptic El mice than that in the parent ddY mice, with binding of
      probes for CREB and c-Myc being unchanged. These results suggest that different
      molecular mechanisms may underlie the expression of being unchanged. These
      results suggest that different molecular mechanisms may underlie the expression
      of AP1 in discrete brain structures of mice with acquired and inherent
      spontaneous seizures.

PMID- 8885294
TI  - Policy ... research that rings true.

PMID- 8885295
TI  - Public health ... senior citizens are turning to exercise faster than any other
      adult group.

PMID- 8885296
TI  - Finance ... digging a new well.

PMID- 8885297
TI  - Consumers ... most people believe that freedom to choose their own health care
      provider is more important.

PMID- 8885298
TI  - Litigation ... the injustice of AIDS.

PMID- 8885299
TI  - Equipment ... transfer more than $4 million of the DoD's medical equipment to
      Indian health care facilities.

PMID- 8885300
TI  - Insurance ... are physician autonomy, quality care, and low cost mutually
      exclusive?

PMID- 8885301
TI  - Guiding light. Will the Justice Department's new antitrust guidelines really make
      a difference to physicians?

PMID- 8885302
TI  - Color me cautious.

PMID- 8885303
TI  - Campaign 1996. The main event.

PMID- 8885304
TI  - Campaign 1996. The incumbent.

PMID- 8885305
TI  - Campaign 1996. The challenger.

PMID- 8885306
TI  - Campaign 1996. The scenarios.

PMID- 8885307
TI  - S.O.S. (Save our societies).

PMID- 8885308
TI  - Paywatch: physician compensation.

PMID- 8885309
TI  - Managed care. A winning market strategy for HMOs.

PMID- 8885310
TI  - Integrated systems. Will super PHOs save the day?

PMID- 8885311
TI  - Insurance. A tax that could leave workers flat.

PMID- 8885312
TI  - HospitalPulse. May 1996.

PMID- 8885313
TI  - Quality watch. Let the compass be your guide.

PMID- 8885314
TI  - Campaign 1996. The lobbyists.

PMID- 8885315
TI  - Levels of certain trace elements in beef and pork imported to Sweden.
AB  - The levels of Pb, Cd, Ni, Cr, Co, Zn, Cu, Mn, As and Se were determined in beef
      and pork imported to Sweden from six different countries. Samples of Swedish beef
      and pork were included for comparison. The results of this survey showed in most
      cases little difference in levels of these elements between the countries and
      agreed well with the results from our previous studies. All results for Pb, Cd,
      Ni and As were below the detection limits of 0.007, 0.001, 0.016 and 0.030 mg/kg
      fresh weight, respectively. Chromium and cobalt were, in both beef and pork,
      close to, or below, the detection limits of 0.004 and 0.003 mg/kg fresh wt,
      respectively. The level of selenium in beef varied considerably between
      countries, from < 0.030 to 0.18 mg/kg fresh wt. The levels of lead and cadmium
      from this study differed strongly in some cases from what have been reported in
      surveys from several countries, among them some countries exporting to Sweden.
      The importance of a rigorous quality control programme is emphasized.

PMID- 8885316
TI  - Lead migration from lead crystal wine glasses.
AB  - Lead release from lead crystal wine glasses was measured at 15 contact times from
      1 min to 24 h (1440 min) in 4% acetic acid and wine at room temperature. Lead
      release at 1 min was equal to approximately 50 and 30% of cumulative lead release
      measured at 30 and 1440 min, respectively, in both extractants. Lead release at
      1440 min was 467 ng/ml in acetic acid and 358 ng/ml in wine. Lead release was
      less in wine (pH 3.14) than in acetic acid (pH 2.39) because of the increased pH
      and ethanol content of wine. Lead release was also measured under conditions that
      simulated consumer use. In experiments with chilled and room temperature wine
      that was steadily removed from vessels during 1-30 min of contact, results were
      not significantly less than results of experiments in which wine temperature was
      20.0 +/- 2.5 degrees C and contact area was constant. In repeated-leaching
      experiments, the total micrograms of lead released in 30 min decreased and was a
      function of 1/L2, where L was leach number. Wine results fit a linear regression
      model of lead release vs square root of time which was previously proposed to
      describe corrosion of lead silicate glass by acetic acid. Slopes and intercepts
      of the square-root-of-time model were used to explain results of repeated
      leaching experiments.

PMID- 8885317
TI  - Aluminium levels in Italian diets and in selected foods from aluminium utensils.
AB  - In Italy, data on aluminium concentration in food items are scarce although
      aluminium containers are widely used to cook, to freeze or to wrap foods (foil)
      and it is known that aluminium can migrate from containers to foods. Therefore,
      an experimental study was carried out to quantify aluminium exposure from
      ingestion of actual total diets and from migration from containers to foods in
      conditions representative of the actual use. Samples of 24 h diets were
      collected, homogenized, lyophilized and the amount of aluminium was determined by
      atomic absorption spectrometry. The aluminium concentrations ranged from 1.0 to
      2.1 mg/kg of food; the intake of aluminium ranged from 2.5 to 6.3 mg/day. The
      amount of aluminium migrating from aluminium cookware was determined by cooking
      various representative foods in aluminium and in glass or stainless steel
      containers. From comparison of the results, the increase in aluminium because of
      migration from cookware was relatively low, with the highest release into acidic
      and salty foods. The daily intake of aluminium even if all the foods were
      prepared and stored in aluminium containers would be approximately 6 mg/day, a
      very low value compared with the Provisional Tolerable Weekly Intake of 7 mg/kg
      body weight (equivalent to 60 mg/day for an adult man) established by the Joint
      FAO/WHO Expert Committee on Food Additives.

PMID- 8885318
TI  - Use of a food composition database to estimate daily dietary intake of nutrient
      or trace elements in Japan, with reference to its limitation.
AB  - Daily dietary intake of 28 trace elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu,
      Ga, Ge, Li, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Si, Sn, Sr, Ti, Tl, V and Zn) were
      estimated from the food intake records (collected by the 24-h total food
      duplicate method), taking advantage of recently published trace element
      composition tables for foods in Japan. Because the number of food items listed in
      the tables was not sufficient, the calculation was made with not all foods
      recorded, and the results should be taken as semi-quantitative. The estimated
      intake was high (i.e. > 1 mg/day as a median) for Al, Cu, Mg, Mn, Si, Sr and Zn,
      medium (i.e. 2-985 micrograms/day) for As, B, Ba, Be, Cr, Ge, Mo, Ni, Sb, Sc, Se,
      Sn and Ti, and low (i.e. < 1 microgram/day) for Cd, Co, Li, Pb and V. Comparison
      of the present estimates with the reported values in the literature on 15
      elements showed that close agreements were observed in the cases of 10 elements
      (i.e. Al, B, Cr, Cu, Mg, Mn, Mo, Ni, Se and Zn) for which the present estimates
      are above 1 microgram/day, whereas the discrepancies were significant for four
      elements (i.e. Cd, Co, Pb and V) with < 1 microgram/day intake. When the expected
      dietary uptake was compared with that by respiration in the cases of the 16
      elements for which the atmospheric concentration data in Japan are available, the
      uptake was exclusively attributable to the dietary route for all 16 elements with
      the possible exception of vanadium.

PMID- 8885319
TI  - The incidence and cause of lasalocid residues in eggs in Northern Ireland.
AB  - Lasalocid is a coccidiostat licensed for use in poultry, but not for use in egg
      laying birds. Lasalocid residues were determined in an egg sample from each of
      161 egg producers in Northern Ireland using liquid chromatography-electrospray
      ionization mass spectrometry, following reports from the Veterinary Medicines
      Directorate concerning the incidence of lasalocid residues in the United Kingdom.
      Approximately 66% of the eggs contained lasalocid residues at concentrations in
      excess of 0.3 ng/g. There was no apparent difference in the incidence of
      lasalocid residues between free range and battery eggs. Carry-over of lasalocid
      from medicated to unmedicated batches of both premix and feed, during milling
      processes, was identified as a possible cause of contamination. Subsequently, egg
      laying birds were fed meal containing a range of lasalocid concentrations,
      similar to those found as a result of unintentional contamination at a feed mill
      (0.1-5.0 mg/kg). The concentrations of lasalocid, measured in their eggs, were
      similar to that found in the survey. Lasalocid persisted in eggs for 10 days
      after withdrawal of medicated feed and replacement with lasalocid-free feed.

PMID- 8885320
TI  - beta-agonists in animal feed. III: Optimization of the clean-up and the end
      determination step.
AB  - This study represents the second part of an interlaboratory study intended to
      develop an official modular Community confirmatory method for the detection of
      beta-agonists in animal feed. Homogeneous pools of primary extracts were prepared
      by means of an extraction module based on the conclusions of a previous part of
      this work. The primary extracts were further processed by four laboratories each
      using a different clean-up scheme. The final extracts thus obtained were cross
      distributed between the same laboratories and measured either by GCMS or HPLC.
      Two laboratories (B and D) applied separate clean-up schemes for clenbuterol and
      salbutamol. All clean-up schemes for clenbuterol were found to be compatible with
      all end-determination steps. In contrast, for salbutamol clean-up method D was
      found not to be compatible with the end-determination steps applied by
      laboratories B and C. The results of this study have clearly demonstrated that
      the clean-up methods for both clenbuterol and salbutamol applied by laboratory B
      yielded superior recoveries with an acceptable standard deviation. Therefore, in
      conclusion to this study, the participating laboratories recommend the clean-up
      schemes applied by laboratory B to serve as part of the official Community
      confirmatory method.

PMID- 8885321
TI  - Application of an enzyme immunoassay for the determination of sulphamethazine
      (sulphadimidine) residues in swine urine and plasma and their use as predictors
      of the level in edible tissue.
AB  - The potential of an enzyme immunoassay (EIA) with high cross-reactivity towards
      the major metabolite (N4-acetyl-sulphamethazine) of sulphamethazine was tested
      for screening fluids and tissues. Healthy pigs were given 20 mg sulphamethazine
      per kg body weight per day in their drinking water for 2 days. Groups of four
      pigs were slaughtered after 3, 4 and 7 days withdrawal. The results were compared
      with liquid chromatographic analysis for urine, plasma, kidney, liver, gluteal
      muscle and diaphragm. In general, concentrations found by the EIA were higher
      than those found by liquid chromatography (LC) because sulphamethazine
      metabolites were detected by the EIA and not by LC. Using the EIA for the
      detection of sulphamethazine and the major metabolite in urine and plasma,
      predictive relationships (tissue-fluid ratios) for the concentration of the
      parent drug in tissue, determined by LC, were calculated. The tissue-plasma
      ratios for muscle, liver and kidney were 0.1, 0.2 and 0.1, respectively. The
      tissue-urine ratios for muscle, liver and kidney were 0.02, 0.03 and 0.03,
      respectively. Owing to the higher concentration of the parent drug in both
      fluids, the presence of the major metabolite in urine and the sensitivity of the
      EIA, tissue can be screened for low concentrations of sulphamethazine.

PMID- 8885322
TI  - Determination of hydrolysed fumonisin B1 in alkali-processed corn foods.
AB  - Treatment of fumonisin B1 (FB1)-contaminated corn with calcium hydroxide solution
      is known to cause large losses of FB1 and formation of the aminopentol AP1 by
      hydrolysis. Methodology was developed for determination of AP1 in foods
      manufactured from calcium hydroxide-processed corn. The ground food (tortilla
      chips, nacho chips, taco shells, or air-dried corn tortillas) was extracted with
      methanol-water (8:2) or methanol-acetonitrile-water (25:25:50), which also
      extracted FB1 and fumonisin B2 (FB2). Clean-up for fumonisin determination was
      carried out on a 1 ml strong anion exchange (SAX) solid phase extraction (SPE)
      column. The water wash from this column, containing AP1, was cleaned up on a 1 ml
      C-18 SPE column. AP1 and, separately, FB1 and FB2 were determined as their o
      phthaldialdehyde-mercaptoethanol (OPA/MCE) and, in some cases, 4-fluoro-7
      nitrobenzofurazan (NBD-F) derivatives by gradient reverse phase liquid
      chromatography with fluorescence detection. Recoveries of AP1, FB1 and FB2 from
      spiked samples were generally satisfactory, but FB1 and FB2 recoveries were low
      with some samples. Better recovery of FB1 with the methanol-acetonitrile-water
      (25:25:50) extraction solvent compared with methanol-water (8:2) was observed for
      naturally-contaminated samples. Detection limits were about 10 ng AP1 per g and
      20 ng FB1 and FB2 per g with OPA/MCE derivatization, but there were interferences
      for FB2. Analysis of 31 samples of alkali-processed corn foods (including three
      known already to contain FB1) showed measurable levels of AP1 in nine samples,
      all < 100 ng/g and lower than the corresponding FB1 concentrations.

PMID- 8885323
TI  - Survey of ethnic foods for mycotoxins.
AB  - A survey has been carried out in the UK to determine the levels of mycotoxins in
      a range of ethnic foods. The survey involved analysis of 121 samples of ethnic
      foods, purchased from specialist shops, for aflatoxins, ochratoxin A and the
      Fusarium mycotoxins (fumonisins, zearalenone and trichothecenes). The samples
      were of cereal and cereal product, fats and oils, nuts and nut products, seeds,
      spices and herbs, pickles, sauces and a variety of canned vegetable and/or pickle
      products. Low concentrations of mycotoxins were present in many samples analysed.
      The types and levels of mycotoxins present varied with the type of sample. The
      most common contaminants were the trichothecenes and ochratoxin A. Trace levels
      of aflatoxins, ochratoxin A, zearalenone, fumonisins and trichothecenes were
      detected in samples containing cereal, such as rice, noodles, corn flour and
      pitta bread. Trace levels of aflatoxins and zearalenone were detected in a sample
      of chili oil and ochratoxin A in a sample of sesame oil. Only one sample of nut
      (almond) contained aflatoxin while aflatoxins, ochratoxin A, zearalenone and
      deoxynivalenol (a trichothecene) were detected in various seeds. Aflatoxins,
      ochratoxin A and fumonisins were found in chili paste and zearalenone and
      ochratoxin A in curry pastes. The highest mycotoxin levels and frequency of
      occurrence were in chili powder, curry powder and ginger.

PMID- 8885324
TI  - Chlorinated pesticides and PCB content in thermal aquaculture of sturgeon
      (Acipenser naccarii).
AB  - One hundred sturgeon (Acipenser naccarii) with an initial weight of about 80 g
      each were fed on wet pellets (3% of live weight) for about 2 years and bred in
      part of the cooling water of a thermoelectric power station. Every 3 months five
      fish were sacrified and muscle samples were collected. Pesticide and PCB
      concentrations were measured by high resolution gas chromatography coupled with
      high resolution mass spectrometry (GC-MS) in the multiple ion detection mode. The
      mean levels of PCBs and DDT metabolites after 24 months of breeding were 28.4 +/-
      2.1 micrograms/kg d.w. respectively. Values were negligible compared with those
      observed in other fish species living in the River Po. Furthermore, a remarkable
      growth of fishes was observed owing to the use of cooling water.

PMID- 8885325
TI  - Determination of heterocyclic amines in flame-grilled fish patty by capillary
      electrophoresis.
AB  - A simple and reliable capillary zone electrophoretic (CZE) method for quantifying
      mutagenic and carcinogenic heterocyclic amines (HCAs) in cooked foods with UV
      visible diode-array detection is described. The buffer system consisted of 50 mM
      disodium hydrogen phosphate, 30 mM sodium chloride, 20 mM citric acid and 26%
      methanol at pH 2.1. An uncoated silica tubing, 51 cm in length, was used for the
      CZE separation. The capillary tubing temperature was maintained at 25 degrees C
      with a constant voltage of 20 kV. The reproducibility of the method was over 95%
      for a five-replicate analysis of 10 micrograms/l-spiked 2-amino-3,4,7,8
      tetramethylimidazo[4,5-f]quinoxaline (4,7,8-TriMeIQx) and the detection limit was
      in the low microgram/l range with coefficients of variation between 6 and 18%. An
      analytical run took only 15 min for 12 known HCAs. Using this procedure, up to 30
      samples could be analysed in a single day. The method is reliable and can be used
      for screening of various HCAs. It has been applied to assess the concentrations
      of heterocyclic amines in otak-otak, a Malay-style grilled fish patty. The major
      mutagenic contaminant found in this foodstuff was 2-aminodipyrido[1,2-a:3',2'
      d]imidazole (Glu-P-2) (286-1068 micrograms/kg), followed by 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) (1.6-13.0 micrograms/kg) and 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ) (14.0-87.5 micrograms/kg). Two co-mutagens
      norharman (NH) and harman (H) were also detected in otak-otak at levels of 2.0
      13.0 micrograms/kg and 12.8-21.3 micrograms/kg, respectively. The substantial
      amount of Glu-P-2 detected in otak-otak is probably a result of the ingredients
      used and the high temperature grilling process.

PMID- 8885326
TI  - Determination of benzo[a]pyrene in lipid-soluble liquid smoke (LSLS) by HPLC-FL.
AB  - We developed a method for the determination of low levels of the carcinogen
      benzo[a]pyrene (BaP) in lipid-soluble liquid smoke (LSLS). The method consists of
      partitioning the LSLS (2 g) between n-hexane and DMSO, purification of the DMSO
      extracts on Sep-Pak C18 Plus and then Silica Plus cartridges, and determination
      of the BaP in the isolated extract by HPLC with fluorescence detection. Detection
      and quantification limits were 0.049 microgram/l (0.024 microgram/kg of LSLS) and
      0.089 microgram/l (0.045 mg/kg), respectively. Recovery (87%) and CV% (< or =
      1.5) were satisfactory.

PMID- 8885327
TI  - Electron transfer reactions in RB90745, a bioreductive drug having both aromatic
      N-oxide and nitroarene moieties.
AB  - The bifunctional hypoxia-specific cytotoxin RB90745, has a nitroimidazole moiety
      attached to an imidazol[1,2-a]quinoxaline mono-N-oxide with a spacer/linking
      group. The reduction chemistry of the drug was studied by pulse radiolysis using
      the one electron reductant CO2.-. As N-oxides and nitro compounds react with CO2.
      at diffusion controlled rates, initial reaction produced a mixture of the nitro
      radical (lambda max 410 nm) and the N-oxide radical (lambda max 550 nm) in a few
      microseconds. Subsequently an intramolecular electron transfer (IET) was observed
      (k = 1.0 +/- 0.25 x 10(3) s-1 at pH 5-9), from the N-oxide to the more electron
      affinic nitro group. This was confirmed by the first order decay rate of the
      radical at 550 nm and formation at 410 nm, which was independent of both the
      concentration of the parent compound and the radicals. The rates of electron
      transfer and the decay kinetics of the nitro anion radicals were pH dependent and
      three different pKas could be estimated for the one electron reduced species: 5.6
      (nitroimidazole group) and 4.3, and 7.6 (N-oxide function). The radicals react
      with oxygen with rate constants of 3.1 x 10(7) and 2.8 x 10(6) dm3 mol-1 s-1
      observed at 575 nm and 410 nm respectively. Steady state radiolysis studies
      indicated four electron stoichiometry for the reduction of the compound.

PMID- 8885328
TI  - The superoxide dismutase-mimic copper-putrescine-pyridine suppresses lipid
      peroxidation in CHO cells. Implications for its prooxidative and antioxidative
      mechanisms of action.
AB  - Copper-Putrescine-Pyridine (Cu-PuPy) is a membrane-permeable complex which
      efficiently dismutates superoxide. In excess of 0.1 mM it is highly cytotoxic and
      oxidizes cellular GSH with concomitant production of H2O2. Here we show that
      treatment of CHO cells with 0.2 mM Cu-PuPy (0-200 min) leads to an accumulation
      of H2O2. Organic hydroperoxides which are also formed at low levels in the
      present of Cu-PuPy, increase significantly after removal of the copper complex.
      We conclude that Cu-PuPy acts as an oxidant until cellular GSH is depleted.
      However, by interfering with radical chain propagation reactions, it suppresses
      lipid peroxidation and thus substitutes for consumed physiological antioxidants
      in a later stage of treatment. This consistently explains our previous, seemingly
      paradox, finding that longer Cu-PuPy treatments may be significantly les toxic
      than shorter ones.

PMID- 8885329
TI  - Redox cycling of human methaemoglobin by H2O2 yields persistent ferryl iron and
      protein based radicals.
AB  - The formation and reactivity of ferryl haemoglobin (and myoglobin), which occurs
      on addition of H2O2, has been proposed as a mechanism contributing to oxidative
      stress associated with human diseases. However, relatively little is known of the
      reaction between hydrogen peroxide and human haemoglobin. We have studied the
      reaction between hydrogen peroxide and purified (catalase free) human metHbA.
      Addition of H2O2 resulted in production of both ferryl haem iron (detected by
      optical spectroscopy) and an associated protein radical (detected by EPR
      spectroscopy). Titrating metHbA with H2O2 showed that maximum ferryl levels could
      be obtained at a 1:1 stoichiometric ratio of haem to H2O2. No oxygen was evolved
      during the reaction, indicating that human metHbA does itself not possess
      catalytic activity. The protein radicals obtained in this reaction reached a
      steady state concentration, during hydrogen peroxide decomposition, but started
      to decay once the hydrogen peroxide had been completely exhausted. The presence
      of catalase, at concentrations around 10(4) fold lower than metHb, increased the
      apparent stoichiometry of the reaction to 1 mol metHb: approximately 20 mol H2O2
      and abolished the protein radical steady state. The biological implications for
      these results are discussed.

PMID- 8885330
TI  - TNF alpha alters mitochondrial membrane potential in L929 but not in TNF alpha
      resistant L929.12 cells: relationship with the expression of stress proteins,
      annexin 1 and superoxide dismutase activity.
AB  - Tumour necrosis factor alpha (TNF alpha) cytotoxicity is mediated, at least in
      part, by oxidative stress and phospholipase A2 activation. The first post
      receptor events to be observed in TNF alpha-sensitive lines are the generation of
      superoxide anion (O2-) within the mitochondria and the activation of
      phospholipase A2. Using the lipophilic dye JC-1 to determine mitochondrial
      membrane potential, we showed that TNF alpha induces time-dependent alterations
      in mitochondrial membrane potential in L929 cells but not in the TNF alpha
      resistant L929. 12 subclone. Heat shock (HS) proteins (HSP) and superoxide
      dismutase (SOD) have been shown to protect cells from TNF alpha cytotoxicity,
      while glucose regulated proteins (GRP) and annexins might also be involved in
      cellular protection. We thus compared the expression of HSP, grp78 and annexin 1
      as well as SOD activity in TNF alpha sensitive and resistant lines. We found no
      difference in the expression of HSP, grp78 or annexin 1, but an increase in the
      constitutive activity of SOD in the L929.12 cells as compared to L929.
      Furthermore, SOD was inducible by TNF alpha in L929 cells, but not in L929.12
      cells. These data suggest that in TNF alpha-resistant lines, mitochondrial damage
      by TNF alpha is prevented by an increase in SOD rather than in overexpression of
      stress proteins or annexins.

PMID- 8885332
TI  - The autoxidation of the reduced forms of EO9.
AB  - The properties of the semiquinone radical from [3-hydroxy-5-aziridinyl-1-methyl-2
      (1H-indole-4,7-indi one)-prop-beta-en-alpha-ol], EO9, have been studied using
      pulse-radiolysis techniques. The reduction potential of the semiquinone of EO9 at
      pH7.4, E(EO9/EO9-), is -253 +/- 6 mV and hence this quinone can be readily
      reduced by one-electron reducing enzymes such as cytochrome P450 reductase and
      xanthine oxidase. However, the radical is unstable in the presence of oxygen (k =
      1.3 +/- 0.15 x 10(8) M-1 s-1). The semiquinone radicals and the hydroquinone are
      in equilibrium although the formation of the hydroquinone is favoured t
      physiologically relevant pH. The hydroquinone of EO9 is also unstable in the
      presence of oxygen and it is predicted that in fully aerated solutions, its half
      life is 1.5 +/- 0.3 seconds. These results are discussed in view of the selective
      cytotoxicity of EO9 and its ability to undergo bioreductive activation by one
      electron reducing enzymes and DT-diaphorase.

PMID- 8885331
TI  - Antioxidant status and susceptibility of sickle erythrocytes to oxidative and
      osmotic stress.
AB  - The purpose of this study was to determine if differences in antioxidant status
      between the red blood cells (RBCs) of sickle cell anemia (SCA) patients and
      controls are responsible for the differential responses to oxidative and osmotic
      stress-induced hemolysis. Susceptibility to hemolysis was examined by incubating
      oxygenated and deoxygenated RBCs at 37 degrees C with 73 mM 2,2' azobis (2
      amidinopropane) HCl (AAPH), a peroxyl radical generator, for up to 3.5 hours.f
      The ability of RBCs to maintain membrane integrity under osmotic stress was
      determined over a range of diluted saline-phosphate buffer. Sickled RBCs showed a
      lesser degree of AAPH-induced hemolysis than control groups and were more
      resistant to osmotic stress-induced hemolysis. SCA patients had higher levels of
      RBC vitamin E and RBC lipids, but lower RBC GSH, plasma lipids and plasma
      carotenes than those of the hospital controls. No significant differences were
      observed in the levels of retinol, vitamin C, vitamin E, MDA and conjugated
      dienes in plasma, or the levels of MDA and conjugated dienes in RBCs. The results
      obtained suggest that the differences in antioxidant status between sickled RBCs
      and controls do not appear to be responsible for their different susceptibility
      to oxidative or osmotic stress-induced hemolysis observed.

PMID- 8885333
TI  - Monoclonal antibodies for detection of 4-hydroxynonenal modified proteins.
AB  - A promising approach to study lipid peroxidation pathology is antibodies
      recognizing aldehydes which react with and became bound to amino acid side chains
      of proteins. We present in this study the characterization of several monoclonal
      antibodies which recognize 4-hydroxynonenal (HNE) modified proteins. Six out of
      20 antibodies recognizing HNE modified BSA were able to detect HNE-protein
      adducts in peroxidized liver microsomes. Two of these antibodies were selected
      and characterized. Both antibodies could also detect HNE-protein adducts in
      oxidized low density lipoprotein. They exhibit no detectable cross reaction with
      proteins modified by malonaldehyde, nonanal, nonanal and 4-hydroxyhexenal.
      Protein bound 4-hydroxyoctenal and 4-hydroxydecenal were recognized to some
      extent. Further characterization revealed that the two antibodies are highly
      selective for HNE bound to histidine with only some cross reaction to HNE bound
      to lysine and cysteine. Preliminary quantitative ELISA-analysis showed that
      oxidized microsomes and oxidized LDL contain 12 nmol and 3 nmol HNE-histidine per
      mg protein respectively.

PMID- 8885334
TI  - Enhanced mitochondrial radical production in patients which rheumatoid arthritis
      correlates with elevated levels of tumor necrosis factor alpha in plasma.
AB  - Mitochondrial dysfunction contributes to cell damage in a number of human
      diseases. One significant mechanism by which mitochondria damage cells is by
      producing reactive oxygen species from the respiratory chain. In this study we
      measured the production of reactive oxygen species by leukocyte mitochondria in
      blood from rheumatoid arthritis patients. To do this we used the
      chemiluminescence of lucigenin, which is accumulated by mitochondria within cells
      and reacts with superoxide to form a chemiluminescent product. By using specific
      inhibitors we could distinguish between the production of reactive oxygen species
      by mitochondria and by NADPH oxidase. There was a five-fold increase in
      mitochondrial reactive oxygen species production in whole blood and monocytes
      from patients with rheumatoid arthritis, when compared to healthy subjects or
      patients with non-rheumatic diseases. There was no increases in mitochondrial
      reactive oxygen species production by neutrophils from rheumatoid arthritis
      patients. The enhanced mitochondrial radical production in rheumatoid arthritis
      patients correlated significantly with increased levels of tumor necrosis factor
      alpha in plasma (p < 0.0001). As tumor necrosis factor alpha is known to increase
      mitochondrial reactive oxygen species production the elevated mitochondrial
      radical formation seen in rheumatoid arthritis patients may be due to activation
      of the mitochondrial radical production. These data suggest that elevated
      mitochondrial oxidative stress contributes to the pathology of rheumatoid
      arthritis.

PMID- 8885335
TI  - Vitamin C prevents oxidative damage.
AB  - Ascorbate-deficiency leads to extensive oxidative damage of proteins and protein
      loss in the guinea pig tissue microsomes as evidenced by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, accumulation of carbonyl, bityrosine as well
      as by tryptophan loss. Oxidative damage is reversed by ascorbate therapy.
      Oxidative damage in ascorbate deficiency also leads to lipid peroxidation in
      guinea pig tissue microsomes as evidenced by accumulation of conjugated dienes,
      malondialdehyde and fluorescent pigment. Lipid peroxides, disappear after
      ascorbate therapy but not by vitamin E. The observations substantiate the
      previous in vitro findings that ascorbate specifically prevents oxidative
      degradation of microsomal membranes. The results indicate that vitamin C may
      exert a powerful protection against degenerative diseases associated with
      oxidative damage and play a critical role in wellness and health maintenance.

PMID- 8885336
TI  - Human (THP-1) macrophages oxidize LDL by a thiol-dependent mechanism.
AB  - The oxidative modification of low-density lipoprotein by macrophages may be an
      important mechanism in the pathogenesis of atherosclerosis. The human monocytic
      leukaemic cell line THP-1, when stimulated with phorbol ester, shares many
      properties with human monocyte-derived macrophages. Oxidation of LDL by these
      cells was characterised by depletion of alpha-tocopherol, increases in
      thiobarbituric acid reactive substances and increases in electrophoretic
      mobility. The LDL particles were also converted to a form which increased
      accumulation of cholesteryl esters within macrophages. The oxidative mechanism
      appeared to be dependent upon the presence of thiols in the cellular medium.
      Oxidation of LDL by THP-1 macrophages, and production of thiols by these cells,
      were dependent upon the presence of L-cystine in the medium. Furthermore,
      cellular oxidation of LDL could be partially mimicked by the addition of cysteine
      to Hams F10 medium. Macrophage-independent oxidation of LDL, mediated by the
      addition of copper ions, was inhibited by cystine and cysteine in phosphate
      buffered saline, but not in Hams F10 medium. The glutathione content of THP-1
      macrophages was also dependent upon the presence of cysteine or cystine in the
      medium, but inhibition of glutathione synthesis by buthionine sulfoximine did not
      prevent the production of thiols or the oxidation of LDL by THP-1 macrophages.

PMID- 8885337
TI  - Bleeding from gastric antral vascular ectasia in marrow transplant patients.
AB  - BACKGROUND: Gastric antral vascular ectasia (GAVE) leads to blood loss in the
      disorders of "watermelon stomach" and portal gastropathy, but is not a commonly
      recognized complication of marrow transplantation. METHODS: GAVE was diagnosed
      when capillary ectasia, focal capillary thromboses, and fibromuscular hyperplasia
      were identified in antral mucosal biopsy specimens. Marrow transplant patients
      bleeding from GAVE were reviewed to ascertain common variables in their
      pretransplant, posttransplant, and bleeding course. RESULTS: Six patients
      developed bleeding due to GAVE. The onset of bleeding was 18 to 94 days after
      transplant and required an average of 37 U of blood (range, 2 to 130 U). Two
      patients stopped bleeding after restoration of platelet counts. Two patients had
      surgical antral resections; both died of multiorgan failure after surgery. Two
      patients had successful endoscopic laser ablation of vascular lesions and
      survived. Factors possibly associated with GAVE included male gender, VOD of the
      liver, oral busulfan as part of the conditioning regimen, and growth factor use
      after transplant. CONCLUSIONS: GAVE was a cause of gastric bleeding in six
      patients with marrow transplant patients. Restoration of platelet counts and
      endoscopic laser photocoagulation are the therapies of choice for ongoing
      bleeding in these patients.

PMID- 8885338
TI  - Complicated PEG-to-skin level gastrostomy conversions: analysis of risk factors
      for tract disruption.
AB  - BACKGROUND: PEG disruptions during conversions to skin-level gastrostomy devices
      have been described, but specific risk factors have not been reported. In this
      study, possible risk factors for tract disruption in a pediatric population were
      identified, and management of complications described. METHODS: The medical
      records of patients who underwent gastrostomy conversions during 1994 were
      reviewed. Statistical analysis was performed using two-tailed student's t test,
      and risk ratios with 95% confidence limits were calculated. RESULTS: Gastrostomy
      tract disruption occurred in 6 to 30 (20%) of tube conversions. Complicated and
      uncomplicated cases did not differ with regard to age, sex, primary or associated
      diagnoses, pregastrostomy or postgastrostomy nutritional status, tract maturity,
      or percutaneous gastrostomy tube type. The use of an 18F obturator-type skin
      level gastrostomy tube increased the risk for gastric separation 4.8-fold. Tract
      disruptions were managed by fluoroscopic gastrostomy tube replacement, repeat
      PEG, or exploratory laparotomy with open gastrostomy. CONCLUSIONS: The use of
      obturator-type skin-level gastrostomy tubes was associated with an increased risk
      of tract disruption. Fluoroscopic verification of intragastric placement is
      warranted after initial conversions to skin-level gastrostomy tubes.

PMID- 8885339
TI  - Nonendoscopic removal of percutaneous endoscopic gastrostomy tubes: morbidity and
      mortality in children.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are often removed by
      cutting the tubing at skin level and allowing the internal components to pass
      through the gastrointestinal tract. This technique is commonly used in adults,
      but little information is available concerning its safety in younger patients.
      METHODS: To assess the safety of this approach in children, the clinical courses
      of all patients who had undergone PEG tube removal in our pediatric
      gastroenterology unit over a 3-year period were reviewed. RESULTS: Five of 11
      patients in whom the internal components were allowed to pass developed
      significant complications. Three required subsequent endoscopic removal of the
      internal component due to persistent vomiting, one died from complications of
      esophageal perforation caused by the retained internal component, and one
      developed a gastrocutaneous fistula containing the retained bumper 2 years after
      PEG tube removal. Significant complications occurred more often in the younger
      and smaller patients. CONCLUSIONS: Small children are at greater risk than adults
      for developing serious complications associated with unremoved PEG tube internal
      components. If passage of the internal components cannot be confirmed after 2
      weeks, chest and abdominal radiographs should be obtained.

PMID- 8885340
TI  - Effects of meperidine on the pancreatic and biliary sphincter.
AB  - BACKGROUND: Opioids are traditionally avoided during sphincter of Oddi manometry
      because of indirect evidence suggesting that these agents cause sphincter of Oddi
      spasm. This study was undertaken to determine the direct effects of meperidine on
      the biliary and pancreatic sphincter. METHODS: Forty-seven patients were
      prospectively evaluated by sphincter of Oddi manometry in the conventional
      retrograde fashion. Manometry was initially performed with intravenous diazepam
      sedation alone. The manometry was repeated 3 to 5 minutes after meperidine was
      administered. RESULTS: The basal sphincter pressure of the biliary sphincter,
      pancreatic sphincter, and the combined sphincter group were not significantly
      altered by meperidine. Concordance (normal versus abnormal) between the basal
      sphincter pressure before and after meperidine was seen in 44 of 47 patients
      (94%). Meperidine produced a significant increase in the pancreatic, biliary, and
      combined sphincter phasic frequency and a significant decrease in the phasic
      duration. The pancreatic and combined sphincter phasic pressures were
      significantly reduced following meperidine administration. Seventeen manometry
      tracings (36%) were believed to be qualitatively better after meperidine, while
      only four (8.5%; p < .001) were qualitatively better with diazepam alone.
      CONCLUSION: Meperidine can be used for additional analgesia during sphincter of
      Oddi manometry if the basal sphincter pressure is the parameter used to determine
      therapy.

PMID- 8885341
TI  - Photodocumentation of total colonoscopy: how successful are endoscopists? Do
      reviewers agree?
AB  - BACKGROUND: Documentation of total colonoscopy usually rests on a statement in
      the endoscopy report indicating that cecal landmarks were visualized. We sought
      to determine whether providing photographs of cecal landmarks provided an
      objective marker of complete colonoscopy. METHODS: We had 12 outside experienced
      endoscopists review 120 photographs of cecal landmarks that had been included
      with colonoscopy reports from our center that included 20 consecutive cases of
      reported total colonoscopy from each of 6 endoscopists. Reviewers graded whether
      they believed each set of photographs documented that at least the cecal inlet
      was reached as definite, probable, or uncertain. RESULTS: There was considerable
      disparity among reviewers as to whether individual photographs documented total
      colonoscopy. The frequency of combined, definite, and probable scores that they
      gave for the 120 photographs ranged from 97% down to 44% (median 82%). Different
      endoscopists also seemed to be variably successful in photodocumenting total
      colonoscopy. Four of the endoscopists received definite and probable scores for
      their 20 cases at least 80% of the time (86% for the highest ranked endoscopist).
      The lowest ranked endoscopist received such scores just 64% of the time.
      CONCLUSIONS: Documenting total colonoscopy with static images of cecal landmarks
      is only partially successful as an objective measure of the extent of total
      colonoscopy.

PMID- 8885342
TI  - Assessment of the course and variations of the hepatic artery in bile duct cancer
      by intraductal ultrasonography.
AB  - BACKGROUND: We evaluated the course and variations of the hepatic artery in bile
      duct cancer using intraductal ultrasonography (IDUS). METHODS: IDUS was used to
      demonstrate the course of the hepatic artery preoperatively in 20 patients with
      extrahepatic bile duct cancer, and the image was compared with angiographic and
      surgical findings. RESULTS: IDUS was able to assess tumor invasion to the main
      branch of the right hepatic artery in all cases. However, it demonstrated only
      three cases in the left hepatic artery and four cases in the proper hepatic
      artery. When the hepatic artery indicated re-entry or bifurcation on the IDUS
      image, the proximal portion of re-entry or bifurcation was established as the
      proper hepatic artery, but when it showed neither re-entry nor bifurcation it was
      established as the right hepatic artery. CONCLUSIONS: IDUS demonstrated the main
      branch of the right hepatic artery in all cases, but was not useful for
      demonstration of the left and proper hepatic arteries. Correct assessment of re
      entry and bifurcation was essential on IDUS images for making the distinction
      between the right hepatic artery and the proper hepatic artery.

PMID- 8885343
TI  - Endoscopic ultrasonographic signs of portal hypertension in cirrhosis.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) has been suggested to investigate
      portal hypertension (PHT). We compared EUS and endoscopy in the exploration of
      PHT in cirrhosis. METHODS: In 58 patients with cirrhosis and 16 controls, the
      presence of esophageal varices and gastric varices was recorded by both endoscopy
      and EUS, peridigestive varices and perforating veins by EUS. Relationships of
      patterns with each other and with clinical and biologic data were evaluated.
      RESULTS: In patients with cirrhosis: esophageal varices were found by endoscopy
      and EUS in 88% and 55% of cirrhotic cases (p < 0.01), and gastric varices in 17%
      and 41%, respectively (p < 0.01). Perforating veins, below the gastroesophageal
      junction, were diagnosed by EUS in 40% of cases and never in controls. A
      significant relationship was found between perforating veins and the following
      patterns: peri-digestive varices, gastric varices at EUS, and esophageal varices
      at endoscopy. In patients with and without cirrhosis: after multivariate
      analysis, only esophageal varices at endoscopy were independently related to
      cirrhosis. However, in Child-Pugh class A patients, both esophageal varices and
      perforating veins were independently related to cirrhosis (diagnostic accuracy,
      92%). CONCLUSIONS: EUS is of limited value in the diagnosis of cirrhosis because
      it gives little additional information to upper gastrointestinal endoscopy. The
      relationships between perforating veins, varices, and peridigestive varices
      support the hypothesis that perforating veins are important in the pathogenesis
      of esophageal and gastric varices.

PMID- 8885344
TI  - A prospective randomized experimental evaluation of three-dimensional imaging in
      laparoscopy.
AB  - BACKGROUND: Restricted depth perception in laparoscopy with two-dimensional
      imaging has been reported to be a major disadvantage of minimally invasive
      procedures. Three-dimensional imaging units have been available for almost 2
      years and are slowly being integrated into endoscopic surgery. So far, potential
      advantages or disadvantages have not yet been studied prospectively. METHODS: We
      evaluated the effects of three-dimensional imaging on surgical performance and
      its influence on surgeons at different experience levels in a prospective
      randomized trial. Twenty participants without laparoscopic experience (novices),
      20 with less than 50 laparoscopic procedures (beginners), and 20 with more than
      50 laparoscopic procedures (advanced surgeons) took part in two different tests
      (tube test and loop test) on a pelvitrainer. In random order, each test was
      conducted using a three-dimensional imaging unit under two-dimensional and three
      dimensional conditions. During each test, the time was measured and the mistakes
      counted. The difference of time and number of mistakes for two-dimensional and
      three-dimensional conditions were calculated for each participant. RESULTS: Speed
      (p < 0.0001) and accuracy (p < 0.0001) were significantly better under three
      dimensional conditions irrespective of the randomized sequence of each individual
      test. Speed was also influenced by individual experience (p > 0.02). Performance
      time decreased by 24.4% +/- 2.8% (m +/- SD), and the number of mistakes decreased
      by 52.5% +/- 27.9% (m +/- SD), as compared with the two-dimensional mode, with no
      significant influence of individual experience. CONCLUSIONS: Three-dimensional
      imaging significantly improves performance (speed and accuracy) regardless of
      previous laparoscopic experience. Thus, three-dimensional imaging may further
      improve the safety aspect of minimally invasive surgery.

PMID- 8885345
TI  - Alterations in pancreatic ductal morphology following polyethylene pancreatic
      stent therapy.
AB  - BACKGROUND: Polyethylene stents placed in the main pancreatic duct induce
      morphologic alterations that may resemble chronic pancreatitis. METHODS: We
      reviewed the sequential pancreatograms of stented patients who had long-term
      follow-up after stent removal. RESULTS: Forty patients (66%) had a normal
      baseline pancreatogram, whereas 21 (34%) showed changes of chronic pancreatitis.
      In 49 of 61 patients (80.3%), one or more had new morphologic changes immediately
      after stent withdrawal graded as mild (69%), moderate (29%), or severe (2%).
      Changes included ductal irregularity (49%), narrowing (35.5%), and side branch
      change (15.5%). Sixteen of the 21 patients (76.1%) with an abnormal baseline
      pancreatogram had worsening of the baseline abnormality or additional changes
      while stented, whereas 33 of 40 (82.5%) with a normal baseline developed new
      morphologic changes. Correlation of stent-induced changes with stent size,
      length, patency at removal, and duration of stenting failed to show an
      association. Twenty-five patients with stent-induced changes had a follow-up
      pancreatogram at a mean of 192 days (10 to 740) after stent removal. There was
      complete resolution of the changes in 64%, partial resolution in 32%, and no
      improvement in 5%. CONCLUSION: Morphologic changes induced by polyethylene
      pancreatic duct stents occurred in 80% of patients. More than one third of these
      changes did not resolve during the follow-up period. Because of concern over
      stent-induced fibrosis, the use of pancreatic stents should remain largely
      experimental.

PMID- 8885346
TI  - Stent-induced pancreatic ductal and parenchymal changes: correlation of
      endoscopic ultrasound with ERCP.
AB  - BACKGROUND: Polyethylene pancreatic duct stents induce morphologic changes of the
      pancreatic duct in the majority of patients. This study was undertaken to
      determine if parenchymal abnormalities are present in patients undergoing short
      term pancreatic duct stenting and to correlate these findings with the
      pancreatogram obtained at stent removal. METHODS: Twenty-five patients underwent
      pancreatic duct stenting and had an endoscopic ultrasound evaluation of the
      pancreas at stent removal. The pancreatograms were evaluated at stent removal for
      ductal irregularity, narrowing, and side branch changes. Endoscopic ultrasound
      was used to assess for differences in the echo characteristics of the pancreatic
      parenchyma around the stent compared with the rest of the gland. RESULTS: Of the
      16 patients evaluated by ERCP at stent removal, 9 (56%) had 1 or more new
      ductographic changes. Endoscopic ultrasound identified parenchymal changes in the
      stented region in 17 of 25 patients (68%). Four patients who had parenchymal
      changes in the stented region on endoscopic ultrasound at stent removal had a
      follow-up study at a mean time of 16 months. Two patients had (new) changes
      suggestive of focal chronic pancreatitis in the stented region. CONCLUSION: Short
      term pancreatic duct stenting induced both ductal and parenchymal changes in more
      than 50% of patients. Chronic pancreatitis may be a consequence of pancreatic
      duct stenting.

PMID- 8885347
TI  - A prospective trial of self-expanding metal stents in the palliation of malignant
      esophageal obstruction after failure of primary curative therapy.
AB  - BACKGROUND: Self-expanding metal stents have been shown to be safe and effective
      for the primary palliation of patients with inoperable malignant esophageal
      obstruction. We sought to determine their safety and efficacy in patients who
      fail curative therapy. METHODS: Seventeen patients with esophageal carcinoma who
      had recurrent dysphagia after radiation, surgery, or chemoradiation therapy for
      esophageal carcinoma were studied. All patients had recurrent dysphagia, and an
      uncovered metal stent was inserted for palliation. Patients were followed-up at 4
      week intervals until death. Palliation was measured by a dysphagia score and the
      Karnofsky index. RESULTS: Seventeen patients with recurrent dysphagia after
      primary treatment with surgery (n = 4), radiation (n = 11), and chemoradiation (n
      = 2) received uncovered Wallstents for palliation of dysphagia. The dysphagia
      score improved by at least 1 point in all patients. Thirteen of 17 patients had a
      2 point improvement in the dysphagia score. The Karnofsky index improved
      significantly (from 58 +/- 3 to 66 +/- 3, p = 0.0002). Fourteen of the 17
      patients had patent stents until death. Three of 12 patients (25%) died of stent
      related complications (bleeding in 1, septic complications in 2 patients).
      CONCLUSIONS: Patients with recurrence of esophageal carcinoma after surgery can
      be successfully treated with metal stents, but patients who have received
      radiation therapy with curative intent may be at greater risk for complications
      because of radiation-induced tumor necrosis and vascular changes in the
      esophageal wall. Larger prospective studies are necessary to clarify this issue.

PMID- 8885348
TI  - Radiation exposure to patients and personnel during interventional ERCP at a
      teaching institution.
AB  - BACKGROUND: This study was designed to determine the radiation dose to patients
      and personnel during ERCP procedures. METHODS: Phantom studies were performed to
      compare dosimetry for two image capture systems and to determine the
      effectiveness of shielding in reducing stray radiation. Radiation techniques and
      dosimetry were recorded in 72 patients undergoing ERCP. RESULTS: Phantom studies
      indicated that increasing fluoroscopy voltage from 75 to 96 kV decreased entrance
      dose by 50%. Image capture by digital radiography decreased radiation exposure by
      66%. Shielding decreased stray radiation exposure by 93%. All patients underwent
      cholangiography (n = 71) and/or pancreatography (n = 53). The mean number of
      interventional ERCP procedures performed per patient was 1.8 (range, 0 to 6). The
      mean measured patient entrance dose was 80 mGy (8 R; range, 0.2 to 73 R);
      however, the calculated mean entrance dose (based on measured intensifying screen
      doses) may have been as high as 3000 mGy (30 R; range, 0.8 to 300 R). Measured
      patient exposure increased with fluoroscopy time (r = 0.9) and with the number of
      interventions performed (r = 0.3). The mean dose to personnel was estimated at
      0.04 mR. CONCLUSIONS: The patient radiation dose depended most on fluoroscopy
      time. The dose may be lowered by minimizing fluoroscopy time, using higher
      voltage and lower current for fluoroscopy, and using digital radiography for
      documentation. Personnel were adequately protected.

PMID- 8885349
TI  - Endoscopic stent therapy for dominant extrahepatic bile duct strictures in
      primary sclerosing cholangitis.
AB  - BACKGROUND: In 15% to 20% of patients with primary sclerosing cholangitis, a
      dominant stricture of the extrahepatic bile ducts may be responsible for
      declining results of serum biochemical liver tests and may contribute to symptoms
      such as jaundice, cholangitis, pruritus, and right upper quadrant pain. METHODS:
      Retrospectively, over the period 1985 to 1994, we evaluated 25 patients who had
      been treated by endoscopic stent therapy after declining results of serum
      biochemical liver tests and symptoms attributable to dominant extrahepatic bile
      duct strictures. Serum biochemical liver test results and symptoms were compared
      before and after treatment. RESULTS: Endoscopic therapy was technically
      successful in 21 patients (84%). In these 21 patients results of all serum
      biochemical liver tests improved significantly (p < 0.001) within 6 months of
      stent therapy. During median follow-up of 29 (2 to 120) months after stent
      removal, 12 patients (57%) remained asymptomatic with stable serum biochemical
      liver tests and 4 (19%) had clinical and biochemical relapse of disease that
      responded favourably to additional endoscopic therapy. Early procedure-related
      complications occurred in 14% of therapeutic endoscopic biliary procedures.
      CONCLUSIONS: Endoscopic stent therapy is a safe and effective treatment modality
      for an acute exacerbation of disease caused by dominant extrahepatic bile duct
      strictures in patients with primary sclerosing cholangitis.

PMID- 8885350
TI  - Brush cytology for pancreatic carcinoma: an analysis of factors influencing
      results.
AB  - BACKGROUND: Despite recent advances in cytology brush design, yield of endoscopic
      brush cytology in suspected pancreatic carcinoma remains low. METHODS: We
      prospectively evaluated 32 such patients by ERCP to analyze differences in yield
      based on anatomic location of the pancreatic stricture, and the role of
      concurrent biliary stricture brush cytology, in improving the overall yield.
      Endoscopic brush cytology was performed on all strictures following ERCP. A final
      diagnosis of pancreatic carcinoma was confirmed in all patients. RESULTS: Twenty
      three of the 32 patients had positive cytology for pancreatic malignancy (71.9%).
      Eight patients had positive brushings from biliary strictures alone (25%) and 15
      had positive brushings obtained from pancreatic strictures (46.9%). The yield
      varied widely depending on the anatomic location of the stricture; ampullary,
      genu, and tail regions had low rates of positive cytology, in part due to
      technical factors and brush design (1 of 8, 2 of 6, and 1 of 4, respectively).
      Strictures of the head and body yielded high rates of positive cytology (7 of 8
      and 4 of 6, respectively). CONCLUSIONS: The yield of endopancreatic brush
      cytology is related to the location of malignancy, with overall yield enhanced by
      concurrent brushing of bile duct strictures.

PMID- 8885351
TI  - Nonpolypoid adenomas of the duodenum in patients with familial adenomatous
      polyposis (Gardner's syndrome).
AB  - BACKGROUND: Although duodenal adenomas are very common in familial adenomatous
      polyposis, we wished to emphasize our experience with finding nonpolypoid
      adenomas in the duodenum of patients with this disease. METHODS: Duodenoscopy was
      performed in 23 patients with an established diagnosis of familial adenomatous
      polyposis or Gardner's syndrome. RESULTS: Endoscopy revealed single or multiple
      nonpolypoid adenomas of the duodenum in 7 patients (30%). The lesions were
      smaller than 5 mm and were endoscopically recognized as flat or depressed reddish
      lesions; one lesion was completely flat and the remaining lesions were flat
      topped elevations with a central depression. All of the lesions were
      histologically diagnosed as tubular adenoma with moderate epithelial atypia.
      CONCLUSION: These findings suggest that duodenal nonpolypoid adenomas are common
      in familial adenomatous polyposis or Gardner's syndrome and that careful
      surveillance endoscopy seems necessary in patients with this disease.

PMID- 8885352
TI  - Gastrointestinal endoscopy in patients taking antiplatelet agents and
      anticoagulants: survey of ASGE members. American Society for Gastrointestinal
      Endoscopy.
AB  - BACKGROUND: Gastrointestinal endoscopy is often required in patients taking
      aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants.
      Because proper guidelines are lacking, we believe that most endoscopists use
      their own criteria and judgment for stopping and restarting these agents during
      the periendoscopic period, and the practice varies widely. The aim of our study
      was to identify these practices among ASGE members. METHODS: Questionnaires, each
      containing 22 questions with 157 responses, were sent to 3300 ASGE members,
      including all Gastroenterology Fellowship Program Directors. One thousand two
      hundred sixty-nine questionnaires were received and analyzed. RESULTS: Physicians
      stopped aspirin and NSAIDs more frequently before colonoscopy (81%) and ERCP
      (79%) than before upper endoscopy (51%) (p < 0.001). Ninety percent of physicians
      stopped aspirin and NSAIDs for 10 or fewer days. Only 20% of physicians performed
      sphincterotomy when aspirin and NSAIDs were not stopped compared with 88% and 85%
      (p < 0.001 for both) of physicians performing cold biopsies at
      esophagogastroduodenoscopy and colonoscopy, respectively, and 77% and 69%
      performing hot biopsies for the same procedures (p < 0.001 for all compared with
      sphincterotomy). Depending on the indication for anticoagulation, 51% to 60% of
      physicians stopped warfarin before upper endoscopy; 71% to 82% before
      colonoscopy; and 26% to 51% of physicians used a "heparin window." All physicians
      restarted warfarin immediately after diagnostic endoscopy, whereas 80% restarted
      it 7 or fewer days after therapeutic endoscopy. CONCLUSIONS: We conclude that a
      wide variation exists regarding the management of aspirin, NSAIDs, and
      anticoagulants in the periendoscopic period. There is a definite need for a
      consensus statement or guidelines for managing patients taking these agents.

PMID- 8885353
TI  - Gastric mucosal biopsy via a nasogastric tube: a nonendoscopic method for
      diagnosing fundic and antral mucosal gastritis and Helicobacter pylori infection
      in man.

PMID- 8885354
TI  - Treatment of esophagorespiratory fistulas with a polyurethane-covered self
      expanding metallic mesh stent.

PMID- 8885355
TI  - Endoscopic ultrasound-guided histologic needle biopsy: preliminary results using
      a newly developed endoscopic ultrasound transducer.

PMID- 8885356
TI  - Endoscopic appearance of Mycobacterium genavense: case report and review of the
      literature.

PMID- 8885357
TI  - Mechanical lithotripsy of pancreatic duct stones.

PMID- 8885358
TI  - Endoscopic band ligation of a Dieulafoy lesion in the small intestine of a child.

PMID- 8885359
TI  - Primary endoscopic retrograde cholecystoendoprosthesis: a nonsurgical modality
      for symptomatic cholelithiasis in cirrhotic patients.

PMID- 8885360
TI  - Resolution of Mirizzi's syndrome using endoscopic therapy.

PMID- 8885361
TI  - Biliary fistula in a patient with HIV cholangiopathy.

PMID- 8885362
TI  - Presumed arteriovenous malformation mimicking hemosuccus pancreaticus of
      Santorini's duct with normal pancreatic anatomy.

PMID- 8885363
TI  - Diagnosis of right hepatic duct injury after cholecystectomy: the use of
      cholangiography through percutaneous drainage catheters.

PMID- 8885364
TI  - Gastric antral vascular ectasia: is there to be a consensus?

PMID- 8885365
TI  - Long-term gastric access: caveat medicus.

PMID- 8885366
TI  - Side-viewing endoscopy in bleeding duodenal diverticula.

PMID- 8885367
TI  - Successful endoscopic dilation of a Crohn's colonic stricture.

PMID- 8885368
TI  - Novel approach to ampullary cannulation.

PMID- 8885369
TI  - Thermospray mass spectral analyses of corynomycolic acids and their derivatives.
AB  - Thermospray mass spectral (TSP-MS) analyses were carried out on methyl
      corynomycolates, their 3-O-acetyl and 3-O-benzoyl derivatives, and on
      corynomycolic acids and their 3-O-acetyl derivatives, using an ion generating
      solvent system consisting of water/isopropanol (99:1, v/v) containing 0.1 M
      ammonium acetate. Methyl corynomycolates generated three groups of peaks
      corresponding to adducts M-18 + H, M + H and M + NH4, while two groups of peaks
      representing adducts M-60 + H and M + H + NH4 were seen in the spectra of 3-O
      acetyl methyl corynomycolates. The 3-O-benzoyl methyl corynomycolates gave a
      series of peaks representing the adducts M-122 + H, M + 2H and M + H + NH4. In
      the spectra of 3-O-acetyl corynomycolic acids, a series of peaks which
      represented M-60 + H and M + NH4 was observed, and in turn, mass spectra of
      corynomycolic acids revealed peaks that represented the adducts M-18 + H and M +
      NH4. Therefore, methyl corynomycolates, 3-O-acyl derivatives of methyl
      corynomycolates,. 3-O-acetylated derivatives of corynomycolic acids and the
      underivatized corynomycolic acids all exhibited the formation of an adduct of the
      anhydro compounds. These anhydro forms were generated by a generalized process.

PMID- 8885370
TI  - A fluorescence quenching study on protoporphyrin IX in a model membrane system.
AB  - The interaction of protoporphyrin IX (3,7,12,15-tetramethyl-8, 13-divinyl-2,18
      porphyrine-dipropionic acid) (PPIX) with unilamellar dimyristoyl-L-alpha
      phosphatidylcholine (DMPC) phospholipid vesicles has been studied by means of
      steady-state fluorescence quenching spectroscopy. The method of fluorescence
      quenching-resolved spectroscopy has been applied in order to resolve the complex
      emission spectrum of a membrane-bound PPIX into two component spectra, attributed
      to distinct fluorophore species with different accessibilities to the iodide
      quencher. It is shown that PPIX associated with liposomes exists in two different
      microenvironments. One part of the fluorophore is embedded inside the lipid
      bilayer and is inaccessible to iodide. Its fluorescence spectrum exhibits the
      maximum characteristic of protoporphyrin found in the apolar medium. The other
      fraction of PPIX is located near the membrane surface, close to the polar
      phospholipid heads. Its emission is blue-shifted, resembling that of PPIX in a
      polar environment. It is quenched by iodide, although it reveals significant
      shielding from the quencher as compared to a buffer PPIX solution. Fluorescence
      quenching using 1-oxyl-4-oxo-2,2,6,6-tetramethyl-piperidine (TEMPONE) does not
      discriminate between the two protoporphyrin species. However, the accessibility
      of protoporphyrin IX to this quencher is much lower in a liposome system than in
      water.

PMID- 8885371
TI  - Determination of pregastric lipase specificity in young ruminants.
AB  - The combined hydrolysis of a chiral triglyceride clearly defined on these three
      positions and of its racemic equivalent reveals all sorts of lipase
      specificities: regioselectivity, typoselectivity and stereospecificity. This
      article describes a study of the pregastric lipases of young ruminants (kid,
      calf, lamb), whose specificity is still somewhat ambiguous. The use of a chiral
      triglyceride in which position sn 1 was occupied by a short-chain fatty acid
      showed that these lipases had dual specificity, i.e. a combination of
      typoselectivity with respect to short-chain fatty acids and sn3
      stereospecificity. A comparison between the performance of the lipase of young
      animals and the fatty acid composition and distribution in the mother's milk
      suggests that the degree of dual specificity in these enzymes is related to the
      characteristics of the mother's milk.

PMID- 8885372
TI  - Long-term imprisonment leads to cognitive impairment.
AB  - The effects of long-term imprisonment on cognitive functions are investigated in
      a longitudinal study. Twenty-four serious offenders in an Austrian penitentiary
      underwent concentration and memory performance measurements via a questionnaire
      presented to them under controlled conditions in two sessions at a 42 month
      interval. The difference in the parameters indicated cognitive impairment after
      this period that was highly significant (P < 0.01); this can be interpreted as a
      direct consequence of imprisonment.

PMID- 8885373
TI  - The speed of post mortem change to the human skeleton and its taphonomic
      significance.
AB  - The aim of this study was to assess the potential speed of post mortem alteration
      to skeletal microstructure by examining human material drawn from differing
      environmental contexts and time periods. The material was taken from terrestrial,
      intertidal and lacustrine contexts and extended over a range of 3 months to 83
      years post mortem. The examination was conducted using backscattered electron
      imaging which provided information on microstructure and relative density. The
      results from this study have significantly brought forward the time of known
      onset for post mortem alteration for 3 morphological types of microstructural
      change, the earliest of which was 3 months post mortem. The contribution of the
      depositing environment was also shown to influence significantly the
      microstructural/ morphological type of post mortem alteration. It is hypothesized
      that microstructural changes to bone could occur within days of death as a result
      of endogenous bacterial migration to the skeleton. Further studies are required
      to establish definitively the earliest moment that such change can occur prior to
      skeletonisation.

PMID- 8885374
TI  - Post mortem markers of chronic alcoholism.
AB  - We compared the post mortem diagnostic value of gamma-glutamyltransferase (GGT),
      carbohydrate-deficient transferrin (CDT), alcoholic liver disease (ALD), blood
      alcohol concentration (BAC), the presence of multiple bruises and poor hygiene of
      the feet as markers of chronic alcoholism (heavy continuous drinking) in 32
      alcoholics with 32 age-sex matched controls drawn from a forensic autopsy
      population. Alcoholics and controls were selected on the basis of positive and
      negative medical history but controls were excluded if BAC exceeded 70 mg%.
      Femoral venous blood, urine and vitreous humour alcohol concentrations were
      determined by headspace gas chromatography (GC). BAC was positive in 19
      alcoholics (mean 234 mg%, range 2-570 mg%) and six controls (mean 32 mg%, range 2
      52 mg%). Serum GGT was measured by a kinetic photometric method, and CDT by both
      isoelectric focusing/laser densitometry and by a commercial radioimmunoassay kit
      (CDTect). Features of alcoholic liver disease were graded histologically using
      two weighted scoring systems. Eleven alcoholics tested positive for GGT, CDTq and
      ALD, nine were positive for two tests, five for one test and three were negative
      for all three tests. No controls were positive for all three tests but six were
      positive for two tests and nine for only one test; 17 were negative for all three
      tests. Using the normal clinical cut-off values GGT, CDTq and CDTect gave poor
      specificity which was improved at moderate cost to sensitivity by raising cut off
      values for each test. Comparison of receiver operating characteristic curves,
      likelihood ratios and post-test odds showed CDT to be the best individual test,
      followed by ALD and GGT. Quantitation of CDT by IEF/laser densitometry performed
      slightly better than MAEC/RIA by CDTect. CDT shows considerable promise as a post
      mortem marker of chronic alcoholism.

PMID- 8885375
TI  - Headspace GC/MS testing for chlorodifluoromethane in two fatal cases.
AB  - Two cases of lethal poisoning due to chlorodifluoromethane (Freon 22) inhalation
      are described. The fluorocarbon was determined in biological tissues by headspace
      gas chromatography/mass spectrometry. Ions monitored were m/z 67, 86 and 51, the
      latter being used for quantification. Blood concentrations were 26.0 and 37.1
      microliters/ml. In both cases, the drug was also identified in urine, vitreous
      humor and bile, but in much lower concentrations.

PMID- 8885376
TI  - Unexpected sudden death of a 12-year-old male with congenital single coronary
      artery.
AB  - A rare autopsy case of a 12-year-old male with a single coronary artery is
      reported in which he suddenly and unexpectedly died after a brief period of
      physical and mental excitation. The single coronary artery originated from the
      left aortic sinus, then branched out the left circumflex artery and afterwards
      descended as the left anterior descending artery, while the right coronary artery
      originated almost at a right angle from the left anterior descending artery. The
      entire heart as well as the cardiac conduction system depended exclusively on the
      single coronary artery for oxygenated blood supply, and the unbalanced blood
      distribution on his exertion probably led to sudden cardiac death. Moreover, in
      this case, both the deceased's mother (at the age of 20 years) and grandmother on
      the mother's side died suddenly, thus suggesting a possibility of maternal
      transmission of this congenital anomaly in his family.

PMID- 8885377
TI  - Kinematics of four methods of stabbing: a preliminary study.
AB  - Despite considerable research and development into stab-resistant clothing, no
      data exists which provides valid data for knife-body contact speeds which may be
      used to ensure that an appropriate and standard protection level is provided.
      Such data can only be obtained by a quantitative kinematic analysis of the
      stabbing movement. Two-dimensional video techniques (50 Hz) were used to record
      images of subjects (n = 10) performing each of four stabbing actions; Long Over
      (LO), Long Under (LU), Short Over (SO), Short Under (SU). Images were digitised
      from a minimum of ten frames pre-, to at least six frames post-blade entry. A two
      way analysis of variance applied to selected kinematic parameters revealed
      significantly higher (P < 0.01) blade entry speeds for LO and LU as compared to
      SO and SU, respectively. This was due to the extra distance over which knife
      speed could be increased in the former conditions. Significantly greater shoulder
      joint angular velocities were found for LU and SU conditions, whilst for the
      elbow joint, conditions LO and SO were significantly greater (P = 0.000008). This
      suggests that the entry speeds during LO and SO are derived from a greater
      contribution from elbow extensor muscles, whilst those for LU and SU are derived
      from a greater contribution from the shoulder flexors. It was concluded that two
      separate kinematic strategies were employed by subjects, and that the maximum
      speed which may be generated during stabbing is influenced by the manner in which
      the knife is held.

PMID- 8885378
TI  - Transport strangulation.

PMID- 8885379
TI  - Polygenic control of a mating signal in Drosophila.
AB  - Recent findings show that traits which influence speciation in the melanogaster
      subgroup of Drosophila can be determined by relatively few loci and/ or be sex
      linked. Using backcrosses between D. simulans and D. mauritiana, we show that an
      acoustic mating signal which plays an important role in courtship (the interpulse
      interval of the 'lovesong') has a polygenic determination. There is no evidence
      of single genes of large effect, a disproportionate contribution of the sex
      chromosome or epistasis. The probability of finding single genes with a large
      effect on sexual isolation may vary with the mode of signalling involved.

PMID- 8885381
TI  - Non-random fertilization in mice correlates with the MHC and something else.
AB  - One evolutionary explanation for the success of sexual reproduction assumes that
      sex is an advantage in the coevolutionary arms race between pathogens and hosts.
      Accordingly, an important criterion in mate choice and maternal selection
      thereafter could be the allelic specificity at polymorphic loci involved in
      parasite-host interactions, e.g. the MHC (major histocompatibility complex). The
      MHC has been found to influence mate choice and selective abortions in mice and
      humans. However, it could also influence the fertilization process itself, i.e.
      (i) the oocyte's choice for the fertilizing sperm, and (ii) the outcome of the
      second meiotic division after the sperm has entered the egg. We tested both
      hypotheses in an in vitro fertilization experiment with two inbred mouse strains
      congenic for their MHC. The genotypes of the resulting blastocysts were
      determined by polymerase chain reaction. We found nonrandom MHC combinations in
      the blastocysts which may result from both possible choice mechanisms. The
      outcome changed significantly over time, indicating that a choice for MHC
      combinations during fertilization may be influenced by one or several external
      factors.

PMID- 8885382
TI  - Protein and microsatellite single locus variability in Salmo salar L. (Atlantic
      salmon).
AB  - We describe genetic variation at three microsatellite single loci and six
      allozyme loci of seven natural Atlantic salmon populations from Ireland and
      Spain. A comparison of genetic variability detected at both types of loci is
      performed. Also, the relative value of microsatellite single locus variability
      with regard to the identification of individual salmon populations is assessed.
      Microsatellite loci are shown to display higher levels of variation than allozyme
      loci. Mean number of alleles (6 +/- 1.53) and heterozygosity (0.46 +/- 0.04) at
      microsatellite loci are greater than those found for allozymes (1.85 +/- 0.05 and
      0.21 +/- 0.03, respectively), and some microsatellite alleles appear to be
      specific for a location or geographical area. Allozyme and microsatellite
      variation show the same pattern of differentiation between populations with Irish
      and Spanish populations grouped into different clusters. However, greater values
      of genetic distance were found among microsatellite (D = 0.0747 +/- 0.011) rather
      than among allozyme loci (D = 0.0449 +/- 0.008). These results provide evidence
      that microsatellite-based analysis of genetic variation will be useful in the
      identification of individual populations of Atlantic salmon.

PMID- 8885383
TI  - On the difficulties of discriminating between major and minor hybrid male
      sterility factors in Drosophila by examining the segregation ratio of sterile and
      fertile sons in backcrossing experiments.
AB  - The observation of segregation ratios of sterile and fertile males in offspring
      samples from backcrossed hybrid females is, in principle, a valid method to
      unveil the genetic basis of hybrid male sterility in Drosophila. When the female
      parent is heterozygous (hybrid) for a sterility factor with major effects, equal
      proportions of fertile and sterile sons are expected in her offspring. However,
      intact (not recombined) chromosome segments of considerable length are expected
      to give segregation ratios that can not be easily differentiated from the 1:1
      ratio expected from a single factor. When the phenotypic character under analysis
      can be determined by combinations of minor factors from the donor species
      spanning a certain chromosome length, very large offspring samples may be needed
      to test this alternative hypothesis against the null hypothesis of a single major
      factor. This is particularly the case of hybrid male sterility determinants in
      Drosophila.

PMID- 8885384
TI  - Two-step chromatographic procedure for purification of basic fibroblast growth
      factor from recombinant Escherichia coli and characterization of the equilibrium
      parameters of adsorption.
AB  - A two-step chromatographic procedure for purification of basic fibroblast growth
      factor (bFGF) from high-cell-density cultures of recombinant E. coli is
      described. Heparin-Sepharose as a material which shows a high affinity to
      endothelial growth factors was used as sorbent for purification of bFGF from the
      soluble cell fraction. A one-step affinity chromatographic procedure resulted in
      very pure bFGF. However, this one-step affinity isolation of bFGF caused the loss
      of around 60% of the recombinant protein. A combination of ion-exchange
      chromatography with heparin-Sepharose affinity chromatography was favored for
      bFGF purification. A first cation-exchange chromatographic step resulted in a
      solution of bFGF with a purity of around 70%. The weak cation exchanger CM
      Sepharose C50 was preferred in comparison to the strong cation exchanger S
      Sepharose because of the higher recovery of bFGF. With the ion-exchange
      chromatographic step prior to the heparin-Sepharose affinity chromatography, the
      total yield of recovery of bFGF increased to 56% compared to 40% using the one
      step purification procedure with heparin-Sepharose. To characterize the
      equilibrium parameters of adsorption, batch experiments for the calculation of
      maximum capacities and dissociation constants for CM-Sepharose C50 and heparin
      Sepharose were carried out. The equilibrium experiments revealed that adsorption
      of bFGF to the ion-exchange sorbent followed single-site interaction according to
      the Langmuir model of adsorption. The adsorption of bFGF to heparin-Sepharose was
      described by a double Langmuir approach of two independent binding sites with
      different maximum capacities and dissociation constants. The purified bFGF showed
      a high biological activity and circular dichroic spectra of a proper folded
      molecule. The analysis of the N-terminal amino acid sequence revealed a mixture
      of two fractions of bFGF, which both are characterized by the cleavage of the
      first amino acid methionine. In addition, half of the bFGF molecules lacked the
      second amino acid alanine.

PMID- 8885385
TI  - Evaluation of micellar electrokinetic capillary chromatography for the analysis
      of selected tobacco alkaloids.
AB  - Micellar electrokinetic capillary chromatography was evaluated for simultaneous
      determination of several tobacco alkaloids with similar molecular structure.
      Satisfactory separation of nicotine, nornicotine, myosmine, anatabine and
      anabasine extracted from tobacco was achieved by introducing an ionic surfactant,
      sodium dodecyl sulfate, into the buffer system at a concentration of 100 mM.
      Sample preparation involved a single extraction with water containing 1%
      triethanolamine. Separation was performed on a 72 cm long, uncoated fused-silica
      capillary. Experimental parameters such as applied voltage, pH value, buffer
      composition and surfactant concentration were optimized. Enhancement of UV
      absorption of alkaloids in the presence of micelles was also studied.

PMID- 8885386
TI  - High-speed particle separation and steric inversion in thin flow field-flow
      fractionation channels.
AB  - The performance of thin (down to 71 microns thick) flow field-flow fractionation
      (flow FFF) channels was examined at both high channel flow-rates (up to
      approximately 47 ml/min) and cross flow-rates (up to approximately 11 ml/min).
      High levels of retention were observed, suggestive of good performance
      characteristics. Supporting this expectation, four sizes (0.04-0.30 microns) of
      polystyrene latex microbeads were baseline separated in under 3 min. Nonetheless,
      a plate height analysis showed that performance was still less than theoretically
      expected. Fast steric-hyperlayer separations of larger latex beads were observed
      in the same systems. Furthermore, it was shown that the steric inversion diameter
      was shifted down to approximately 0.23 micron thus expanding the size range to
      which this FFF mode is applicable. The steric inversion phenomenon observed using
      narrow latex standards was shown to be consistent with that found for a
      polydisperse polyvinylchloride latex.

PMID- 8885387
TI  - Computerized genetic map of Bacillus subtilis.

PMID- 8885388
TI  - Specific detection of Candida albicans and Candida tropicalis by fluorescent in
      situ hybridization with an 18S rRNA-targeted oligonucleotide probe.
AB  - In situ hybridization of whole cells with rRNA-targeted, fluorescently labelled
      oligonucleotide probes is a powerful method to specifically detect microorganisms
      in their natural habitat without cultivation and subsequent identification by
      phenotypic characterization. To examine the use of this method for the specific
      detection of pathogenic Candida species, we have designed an oligonucleotide
      probe which binds to the 18S rRNA of C. albicans and C. tropicalis, the two most
      important pathogenic Candida species, and differentiates them from other
      clinically relevant species. After establishing suitable hybridization
      conditions, we confirmed the specificity of our probe O20 in RNA dot blot
      hybridizations with a series of reference strains and clinical isolates of
      medically important Candida species. All C. albicans and C. tropicalis strains
      hybridized with the probe, whereas all strains of C. parapsilosis, C. glabrata,
      C. krusei, C. guilliermondii, C. kefyr and C. lusitaniae did not. When we used
      the fluorescently labelled probe O20 to specifically detect single cells of the
      two target species by in situ hybridization, both C. albicans and C. tropicalis
      reacted strongly with the probe and could be clearly differentiated from C.
      krusei and C. parapsilosis, although the latter organism contains only two
      nucleotide mismatches in the probe target region. This discrimination capacity
      was also seen when mixed suspensions of C. albicans and C. parapsilosis were
      hybridized with the probe. After infection of a human endothelial cell line with
      C. albicans and C. krusei, C. albicans cells adhering to the endothelial cells
      were easily distinguishable from the C. krusei cells by fluorescent in situ
      hybridization with probe O20. In addition, germ tubes and hyphae of C. albicans
      were also efficiently labelled. The application of fluorescently labelled rRNA
      targeted oligonucleotide probes therefore appears to be a valuable tool for the
      specific detection and identification of different members of the genus Candida,
      which does not require any cultivation.

PMID- 8885389
TI  - Candida albicans adherence to a human oesophageal cell line.
AB  - The oesophageal epithelium appears to be one of the primary cell targets of
      Candida albicans in AIDS patients. To study this interaction, we have established
      an in vitro adherence assay using a human epithelial oesophageal cell line (HET1
      A). When yeast cells were grown in 500 mM D-galactose, adherence increased
      significantly over cultures prepared in 500 mM D-glucose. In addition to HET1-A
      cells, adherence of the organism grown in D-galactose to human buccal epithelial
      cells and a murine alveolar macrophage cell line was also higher. Adherence of
      yeast cells to HET1-A cells was partially inhibited in the presence of D
      glucosamine or N-acetyl-D-glucosamine, but not with D-mannose, D-glucose, L
      fucose or D-galactose. Attachment to HET1-A cells was studied using scanning and
      transmission electron microscopy. Partial phagocytosis of adhering yeast cells
      was observed occasionally within the first 90 min following infection, as
      evidenced by the formation of HET1-A pseudopodia in instances of close contact
      with yeast cells. The influence of D-galactose on cell surface proteins was
      studied by analysing beta-mercaptoethanol-extracted proteins from yeast cells
      grown in either 500 mM D-galactose or D-glucose. From D-galactose-grown cells
      only, a glycoprotein of approximately 190 kDa was observed in Aurodye-stained SDS
      PAGE gels and in Western blots using an immunoglobulin fraction (IgG) prepared
      from sera of rabbits infected with the organism. These studies demonstrate that
      C. albicans adheres to human oesophageal cells and may utilize cell surface
      proteins whose synthesis is nutritionally regulated.

PMID- 8885390
TI  - Multiply antibiotic-resistant Streptococcus pneumoniae recovered from Spanish
      hospitals (1988-1994): novel major clones of serotypes 14, 19F and 15F.
AB  - We analysed a collection of 95 multiply antibiotic-resistant pneumococci,
      recovered since 1988 from 14 Spanish hospitals, that have MICs > or = 0.25
      microgram benzylpenicillin ml-1. The majority of the isolates were of serogroups
      14, 23, 6, 19 and 15, which are currently the serogroups mainly associated with
      multiresistance in Spain. All of the serogroup 23 isolates were members of the
      major Spanish serotype 23F multiresistant clone. Similarly, most of the serogroup
      6 isolates were members of the major multiresistant serotype 6B clone, or
      variants of this clone. Eighteen of the 24 isolates of serogroup 19 were members
      of a highly penicillin-resistant clone that appears to be a serotype 19F variant
      of the major Spanish serotype 23F multiresistant clone. Eighteen of the 25
      isolates of serotype 14 were members of a previously uncharacterized highly
      penicillin-resistant clone. Thirteen of the 16 isolates of serogroup 15 were
      members of a single previously unreported clone of serotype 15F that had moderate
      levels of resistance to penicillin. Approximately 65% of the multiresistant
      pneumococci that are currently circulating in Spain were members of the three new
      clones of serotype 14, 15F and 19F that we describe here, or the previously
      described serotype 6B and 23F clones. The other 35% of isolates were minor
      variants of the major clones, unrelated minor clones, and unique isolates, many
      of which appeared to have arisen by horizontal gene transfer events.

PMID- 8885391
TI  - P-fimbriae-producing septicaemic Escherichia coli from poultry possess fel
      related gene clusters whereas pap-hybridizing P-fimbriae-negative strains have
      partial or divergent P fimbrial gene clusters.
AB  - The organization of P fimbrial gene clusters of 13 papC-hybridizing Escherichia
      coli strains isolated from poultry with colisepticaemia, five P-fimbriae
      expressing (P-positive) and eight P-fimbriae-non-expressing (P-negative), were
      examined by PCR and by Southern blot hybridization using primers or gene probes
      specific to the I, B, A, C or G genes. The absence of P fimbrial expression was
      associated with lack of PCR amplification of one or more of these genes, most
      commonly the I gene. Restriction endonuclease EcoRI, BamHI or PstI digests of
      genomic DNA from all strains hybridized with each of the gene probes and
      demonstrated polymorphisms between P-positive and P-negative strains. PstI
      digests of DNA from 12 of the 13 strains, when hybridized with the A gene probe,
      demonstrated a 0.1 kb fragment specific to the felA gene which encodes the major
      structural protein of F11 fimbriae. Hence, only the P-positive strains contained
      complete copies of fel-related gene clusters. In contrast, most of the pap
      hybridizing P-negative strains contained partial or divergent P fimbrial gene
      clusters, which explains the lack of P fimbrial expression by these strains.

PMID- 8885392
TI  - Motility mutants of Vibrio cholerae O1 have reduced adherence in vitro to human
      small intestinal epithelial cells as demonstrated by ELISA.
AB  - Vibrio cholerae must colonize the human small intestine to cause diarrhoeal
      disease. V.cholerae strains N16961 (EI Tor, Inaba) and 395 (classical, Ogawa)
      adhered to the epithelial cell surface and the mucus layer of isolated human
      small intestinal epithelial cells. They adhered specifically to the mucosa and
      apical membrane in thin sections of small intestine. No binding to the
      basolateral membrane of dissected epithelial tissue or to intracellular
      components of the epithelial cells was observed by either light or indirect
      immunofluorescence microscopy. Based on these results, a modified ELISA was
      developed to quantitatively study adherence of V. cholerae to human small
      intestinal epithelial cells. The assay used homogenized human small intestinal
      mucosal tissue as the substrate for binding. Treatment of the epithelial cell
      homogenate with 2-mercaptoethanol to disrupt protein and glycoprotein secondary
      structure inhibited the binding of V. cholerae strains, suggesting that binding
      was to specific receptors. Several V. cholerae strains and mutants from both
      biotypes were tested for adherence in the modified ELISA. Wild-type strains of
      both biotypes and non-enterotoxigenic strains, which were known to colonize
      humans, adhered. V. cholerae mutants defective in motility, flagellar structure
      of chemotaxis, which were known to exhibit reduced colonization in animal models,
      exhibited decreased adherence. The specificity of the assay and its ability to
      quantify binding should facilitate identification and the study of adherence
      factors involved in the colonization of human small intestinal epithelial cells
      by V. cholerae.

PMID- 8885393
TI  - Chemotactic responses to an attractant and a repellent by the polar and lateral
      flagellar systems of Vibrio alginolyticus.
AB  - Chemotactic responses in Vibrio alginolyticus, which has lateral and polar
      flagellar systems in one cell, were investigated. A lateral-flagella-defective
      (Pof+ Laf-) mutant, which has only a polar flagellum, usually swam forward by the
      pushing action of its flagellum and occasionally changed direction by backward
      swimming. When the repellent phenol was added, Pof+ Laf- cells moved frequently
      forward and backward (tumbling state). The tumbling was derived from the frequent
      changing between counter-clockwise and clockwise (CW) rotation of the flagellar
      motor, as was confirmed by the tethered-cell method. Furthermore, we found that
      the tumbling cells did not adapt to the phenol stimulus. When the attractant
      serine was added, the phenol-treated cells ceased tumbling and swam smoothly,
      adapting to the attractant stimulus after several minutes. We isolated chemotaxis
      defective (Che-) mutants from the Pof+ Laf- mutant; the tumbling mutants were not
      isolated. One interesting mutant swam backwards continuously, with its flagellum
      leading the cell and its flagellar motor rotating CW continuously. A polar
      flagella-defective mutant (Pof- Laf+) stopped swimming after phenol addition and
      then recovered swimming ability within 10 min, indicating that lateral flagella
      can adapt to the repellent stimulus. This may represent a functional difference
      between the two flagellar systems in Vibrio cells, and between the chemotaxis
      systems affecting the two types of flagella.

PMID- 8885394
TI  - Isolation of an IHF-deficient mutant of a Pseudomonas aeruginosa mucoid isolate
      and evaluation of the role of IHF in algD gene expression.
AB  - The role of integration host factor (IHF) in the regulation of alginate synthesis
      was investigated in a mucoid strain of Pseudomonas aeruginosa (strain CHA)
      isolated from a cystic fibrosis patient. Escherichia coli strain BL21(DE3) was
      made IHF-deficient by inactivation of its chromosomal IHF genes, himA and himD,
      then used as host strain to overproduce P. aeruginosa IHF. The purified
      recombinant IHF protein was used to determine the affinity of IHF for the two IHF
      binding sites in the algD promoter. The Kd values were determined to be 130 nM
      for algD IHF site 2 and about 2 microM for algD IHF site 1. Two IHF-deficient
      mutants of P. aeruginosa strain CHA were constructed by insertional inactivation
      of the himA gene, and the activity of the algD promoter was determined using
      transcriptional fusion with xylE as reporter gene. The expression of algD, the
      structural gene for GDP-mannose dehydrogenase, was decreased three- to fourfold
      in the himA mutants under conditions of high salinity and nitrogen limitation.
      Assays of alginate production by cultures grown on agar plates indicated that the
      IHF-deficient mutants synthesized 50% less polymer than the mucoid parental
      strain. These results demonstrate clearly that although IHF is dispensable for
      alginate production, himA expression is required for full activation of algD
      expression.

PMID- 8885395
TI  - Functional definition of regions necessary for replication and incompatibility in
      the Mycobacterium fortuitum plasmid pAL5000.
AB  - Different parts of the Mycobacterium fortuitum plasmid pAL5000 necessary for
      plasmid replication and incompatibility were defined and studied. Two ORFs, named
      repA and repB, were defined which are necessary for replication. A pAL5000
      derivative deleted in these genes can be made to replicate by providing the gene
      products in trans. A 435 bp fragment was defined which was necessary in cis for
      replication and which had an influence on copy number. This region (inc), which
      contains several repeated motifs, was also able to confer a degree of
      incompatibility when cloned into an otherwise unrelated mycobacterial replicon.
      pAL5000-derived plasmids carrying two copies of the inc region had a lower copy
      number and were less stable than the wild-type. These effects were only observed
      when the two regions were in the same orientation. Plasmids carrying only the inc
      region and no other parts of pAL5000 could be made to replicate if repA and repB
      were supplied in trans from another plasmid. Based on these findings, systems for
      selectively curing cells of one plasmid of a pair were designed and shown to be
      functional in Mycobacterium smegmatis. These have potential as a simple delivery
      system for achieving transposon mutagenesis or gene replacement in mycobacteria.

PMID- 8885396
TI  - Mutants of Streptomyces roseosporus that express enhanced recombination within
      partially homologous genes.
AB  - Streptomyces roseosporus mutants that express enhanced recombination between
      partially homologous (homeologous) sequences were isolated by selection for
      recombination between the bacteriophage phi C31 derivative KC570 containing the
      Streptomyces coelicolor glucose kinase (glk) gene and the S. roseosporus
      chromosome. The frequencies of homeologous recombination in the ehr mutants were
      determined by measuring the chromosomal insertion frequencies of plasmids
      containing S. coelicolor glnA or whiG genes. S. roseosporus ehr mutants showed
      10(2)- to 10(4)-fold increases in homeologous recombination relative to Ehr+
      strains, but no increase in homologous recombination. Southern hybridization
      analysis revealed single unique sites for the insertion of each of the plasmids,
      and the crossovers occurred in frame and in proper translational register,
      yielding functional chimeric glnA and whiG genes.

PMID- 8885397
TI  - An amplifiable and deletable locus of Streptomyces ambofaciens RP181110 contains
      a very large gene homologous to polyketide synthase genes.
AB  - Streptomyces ambofaciens RP181110 produces the macrolide polyketide spiramycin.
      Like many other Streptomyces species, the RP181110 strain is prone to genetic
      instability involving genomic rearrangements (deletions and/or amplifications) in
      the large unstable region of the genome. It has previously been demonstrated that
      the amplification of a particular locus (AUD205) affects spiramycin biosynthesis
      and, conversely, the loss of this amplification is correlated with the
      restoration of antibiotic production. This report focuses on a 0.93 kb reiterated
      fragment specific for the AUD205 locus. Sequencing of 3596 bp including this
      reiteration revealed the presence of an ORF (orfPS) whose potential product was
      highly homologous to the EryA and Raps proteins, responsible for the biosynthesis
      of erythromycin in Saccharopolyspora erythraea and rapamycin in Streptomyces
      hygroscopicus, respectively. orfPS encodes a protein with at least four
      successive domains: ketoacyl synthase, acyltransferase, ketoreductase and acyl
      carrier protein. This organization is very similar to most eryA and rap modules.
      The reiterated sequence corresponds to the acyltransferase domain. orfPS was
      transcribed during rapid growth and stationary phase in RP181110 and
      overtranscribed in the amplified mutant. Both these results suggest that the gene
      encodes a type I polyketide synthase and its reorganization is responsible for
      the loss of spiramycin production in the amplified strains.

PMID- 8885398
TI  - Mutational analysis and chemical modification of Cys24 of lactococcin B, a
      bacteriocin produced by Lactococcus lactis.
AB  - Using site-directed mutagenesis the single cysteine residue at position 24 of
      lactococcin B was replaced by all other possible amino acids. Most of these
      mutant molecules retained bacteriocin activity, with the exception of those in
      which cysteine was replaced by a positively charged amino acid. This would seem
      to be in agreement with the authors' earlier observation that treatment of the
      wild-type molecule with HgCl2 resulted in its inactivation. The factor that
      causes inactivation of lactococcin B seems to be the introduction of a positive
      charge at position 24 by HgCl2 rather than oxidation of this residue, as
      treatment of the bacteriocin with other oxidative chemicals did not interfere
      with the ability of lactococcin B to dissipate the membrane potential of
      sensitive cells. Results are also reported which imply that inactive lactococcin
      B can still bind to its receptor. It can be replaced by an active bacteriocin
      molecule, resulting in dissipation of the membrane potential.

PMID- 8885400
TI  - Uptake-sequence-independent DNA transformation exists in Neisseria gonorrhoeae.
AB  - A DNA transformation dose-response curve of piliated (P+) gonococci with the use
      of cloned DNA containing a pilE2-cat fusion showed saturation at high and low
      levels of transforming DNA. At low DNA concentrations, transformation of the P+
      strain MS11-A was effectively inhibited by a 1000-fold molar excess of the
      gonococcal transformation uptake sequence (GCUS). The same molar excess of the
      GCUS did not inhibit transformation of MS11-A at high DNA concentrations. In MS11
      B2, a nonpiliated (P-), pilin-nonproducing, isogenic variant of MS11-A, the GCUS
      did not inhibit transformation at any level of transforming DNA. These data
      suggest that two mechanisms of transformation exist in P+ cells: one which
      utilizes the GCUS and one which does not. In MS11-B2 P- cells, no evidence was
      found for the presence of the GCUS-dependent mechanism, suggesting that
      transformation in this background occurs solely by the GCUS-independent
      mechanism.

PMID- 8885402
TI  - Molecular biological evidence for the occurrence of uncultured members of the
      actinomycete line of descent in different environments and geographical
      locations.
AB  - A 16S rDNA based molecular ecological study was performed on a sample taken from
      a peat bog in Germany. Total DNA was extracted by directly lysing micro-organisms
      in the peat matrix. The 5' 1400 nucleotides of the bacterial 16S rDNA were
      amplified using conserved bacterial PCR primers. A clone library was generated by
      blunt-end cloning and 262 16S rDNA clones were analysed. Of these, 37 were
      located in the Gram-positive phylum, as determined by hybridization to an
      oligonucleotide probe specific for Gram-positive bacteria. Analysis of 17 of
      these clones by sequence analysis and their comparison with published sequences
      representing all of the main bacterial phyla indicated their membership of the
      actinomycete line of descent. These peat clones were found to represent three
      novel lineages, two of which appear to be related to the species Acidimicrobium
      ferrooxidans, and 'Candidatus Microthrix parvicella'. Clone sequences of the
      third group are phylogenetically related to Rubrobacter radiotolerans. Comparison
      with short 16S rDNA clone sequences obtained from DNA isolated from a
      geothermally heated soil in New Zealand, and from DNA isolated from soil in
      Australia, Japan and Finland and marine environments from the Atlantic and the
      Pacific Oceans, suggests that members of these three groups occur in very
      different environments across the world.

PMID- 8885403
TI  - Dependence of peptidoglycan metabolism on phospholipid synthesis during growth of
      Escherichia coli.
AB  - The role of phospholipid synthesis in peptidoglycan metabolism during growth of
      Escherichia coli was determined. The inhibition of phospholipid synthesis,
      achieved by inhibiting fatty acid synthesis with cerulenin or by glycerol
      deprivation of gpsA mutant strains, resulted in the concomitant inhibition of
      peptidoglycan synthesis. These effects on peptidoglycan synthesis were relatively
      specific in that the treatments did not cause a general inhibition of
      macromolecular synthesis. Furthermore, the inhibition of phospholipid synthesis
      also resulted in the rapid development of penicillin tolerance. It was unlikely
      that penicillin tolerance in these cases were simply due to the inhibition of
      growth caused by cerulenin treatment or glycerol deprivation because treatments
      with more effective growth inhibitors, e.g. chloramphenicol or norfloxacin, did
      not confer penicillin tolerance. Penicillin tolerance was shown to be a direct
      consequence of the inhibition of phospholipid synthesis and not due to the
      possible accumulation of guanosine-3',5'-bispyrophosphate (ppGpp), the starvation
      stress signal molecule known to be responsible for the development of penicillin
      tolerance in amino-acid-deprived bacteria. Therefore, peptidoglycan metabolism is
      coupled to phospholipid synthesis during growth of E. coli, and this may
      represent an important means to ensure the coordination of cell envelope
      synthesis in growing bacteria.

PMID- 8885404
TI  - The O polysaccharide chain of the lipopolysaccharide from Vibrio cholerae O76 is
      a homopolymer of N-[(S)-(+)-2-hydroxypropionyl]-alpha-L-perosamine.
AB  - Chemical and serological studies of LPS from Vibrio cholerae O76 (O76) were
      performed. The LPS of O76 contained D-glucose, D-galactose, L-glycero-D-manno
      heptose, D-fructose, D-glucosamine, D-quinovosamine (2-amino-2,6-dideoxy-D
      glucose) and L-perosamine (4-amino-4,6-dideoxy-L-mannopyranose). The sugar
      composition of the LPS from O76 was quite similar to that of LPS from V. cholerae
      O1 with the exception of the presence of a small amount of D-galactose in the LPS
      of O76. However, perosamine, a major sugar component of the LPS from O76, was in
      the L configuration in contrast to the D configuration of the perosamine in the
      LPS of V. cholerae O1. The L-perosamine was N-acylated with an (S)-(+)-2
      hydroxypropionyl group in the LPS from O76. Structural analysis by NMR
      spectroscopy, as well as GC/MS, revealed that the O polysaccharide chain of the
      LPS from O76 was an alpha(1-->2)-linked homopolymer of N-[(S)-(+)-2
      hydroxypropionyl]-L-perosamine. The serological cross-reactivity between the LPS
      of O76 and the LPS from other strains, such as V. cholerae O1 (Ogawa and Inaba O
      forms), Vibrio bio-serogroup 1875 (Original and Variant strains), V. cholerae
      O140 (Hakata) and Yersinia enterocolitica O9, was examined in passive haemolysis
      tests with sheep red blood cells that had been sensitized with LPS and antisera
      raised against whole cells of these bacteria. The latter six strains have in
      common the O antigen that includes Inaba antigen factor C, in addition to their
      own O-antigenic factors. Thus, they crossreact serologically. The O
      polysaccharide chains of the LPS of these six trains are known to consist
      exclusively of alpha(1-->2)-linked D-perosamine homopolymers and differences are
      found only among the N-acyl substituents. In passive haemolysis tests, the LPS of
      O76 did not cross-react serologically with any of the other LPS examined. Thus,
      the results obtained in this study support the hypothesis that Inaba antigen
      factor C, associated with the O antigens of these six strains, which include V.
      cholerae O1, is related substantially and exclusively to their alpha(1-->2)
      linked homopolymers of N-acylated D-perosamine, and not to such homopolymers of N
      acylated L-perosamine.

PMID- 8885405
TI  - The response of selected members of the archaea to the gram stain.
AB  - Archaea possess a broader range of cell envelope structural formats than
      eubacteria and their cell walls do not contain peptidoglycan. Some archaea have
      only a single S-layer as their cell wall (e.g. Methanococcus jannaschii and
      Sulfolobus acidocaldarius), whereas others have multiple layers (e.g.
      Methanospirillum hungatei). Sometimes there can also be a high proportion of
      tetraether lipids in membranes to make the envelope more resilient to
      environmental stress (e.g. Methanococcus jannaschii and Sulfolobus acidocaldarius
      grown at 70 degrees C). Since the Gram reaction depends on both the structural
      format and the chemical composition of the cell envelope of eubacteria, it was
      important to determine if the same is true for archaea. Methanospirillum
      hungatei, Methanosarcina mazei, Methanobacterium formicicum, Methanococcus
      jannaschii and Sulfolobus acidocaldarius, chosen because of their different
      envelope formats and chemistries, were subjected to a Gram stain that can be used
      for transmission electron microscopy. In this staining regimen, the iodine is
      replaced by potassium trichloro(eta 2-ethylene)platinate(II) as the mordant, and
      the platinum of the new compound is the electron-scattering agent for electron
      microscopy. Of all these archaea, only Methanobacterium formicicum stained Gram
      positive since its pseudomurein wall remained intact; the platinum compound
      formed large electron-dense aggregates with the crystal violet that were located
      in the vicinity of the cell wall and the plasma membrane. All but the terminal
      filament cells of Methanospirillum hungatei stained Gram-negative because the
      limiting porosity of its external sheath was so small that the Gram reagents
      could not enter the cells. The terminal cells of filaments stained Gram-positive
      because the staining reagents gained entry through the terminal plugs. All other
      archaea stained Gram-negative because their cell walls were so disrupted during
      staining that the crystal violet-platinum complex could not be retained by the
      cells. Methanococcus jannaschii was grown at both 50 degrees C and 70 degrees C
      so that the tetraether lipids in its plasma membrane could be increased from 20%
      (50 degrees C) to 45% (70 degrees C) of the total lipids; in both cases the cells
      stained Gram-negative.

PMID- 8885406
TI  - SPR28, a sixth member of the septin gene family in Saccharomyces cerevisiae that
      is expressed specifically in sporulating cells.
AB  - The septins are a recently recognized family of proteins that are present in a
      wide variety of fungal and animal cells, where they are involved in cytokinesis
      and apparently in other processes involving the organization of the cell surface.
      Five previously described Saccharomyces cerevisiae septins are associated with
      the neck filaments of vegetative cells and/or with the developing prospore wall
      of sporulating cells. We report here the characterization of SPR28, a sixth
      member of the S. cerevisiae septin gene family whose existence was revealed by
      the yeast genome project. Analysis of mRNA levels showed that SPR28 is a new
      member of the group of "late genes' that are expressed at high levels during the
      meiotic divisions and ascospore formation. The septin it encodes, Spr28p,
      exhibited specific two-hybrid interactions with itself and with three other
      septins that are expressed in sporulating cells. Consistent with these results,
      an Spr28p-green fluorescent protein fusion was induced during meiosis I and
      appeared to be associated with the developing prospore walls. Deletion of SPR28
      in either a wild-type or an spr3 delta background produced no obvious
      abnormalities in vegetative cells and had little or no effect on sporulation,
      suggesting that the septins have redundant roles during spore formation.

PMID- 8885409
TI  - Detection of genetic variation in Ustilago maydis strains by probes derived from
      telomeric sequences.
AB  - Genetic variation using probes derived from telomeric sequences was analysed
      among several Ustilago maydis strains in an attempt to identify discriminative
      fingerprint patterns. Three groups of wild isolates from different geographical
      areas and one group of standard laboratory strains were examined. Analysis of the
      endmost restriction fragments (EFs) and of the endmost-associated restriction
      fragments (EAFs) of the chromosomes revealed group differences. Most of the EFs
      in two groups of strains showed a similar length whereas in the other two groups
      they were distributed in classes of different lengths. Furthermore, analysis of
      the EAFs permitted possible fingerprint patterns to be predicted for each group
      of strains based on the occurrence of amplified bands as well as the presence or
      absence of distinct bands which were shown to be present in terminal as well as
      in interstitial sites of the chromosome. The approach evaluated in this work
      yielded highly polymorphic fingerprint patterns and could be used to distinguish
      groups of fungal isolates; this approach may also be effective for other fungal
      systems.

PMID- 8885407
TI  - The extracellular acid protease gene of Yarrowia lipolytica: sequence and pH
      regulated transcription.
AB  - The gene encoding an acid extracellular protease (AXP) from Yarrowia lipolytica
      (Candida olea) 148 was cloned and the complete nucleotide sequence was
      determined. The amino acid sequence deduced from the nucleotide sequence reveals
      that the mature AXP consists of 353 amino acids with an M, of 37427. The gene
      also encodes a putative 17 amino acid hydrophobic prepeptide and a 27 amino acid
      propeptide containing no potential N-glycosylation sites. The mature
      extracellular enzyme is produced by cleavage between Phe and Ala. AXP is a member
      of the aspartyl family of proteases. AXP shows homology to proteases of several
      fungal genera and to human progastricin. The coding sequence is preceded by a
      potential regulatory region of 1982 bp. Transcription of both AXP and alkaline
      extracellular protease genes of Y. lipolytica 148 is regulated by the pH of
      culture.

PMID- 8885410
TI  - Glycerol is not an inhibitor of mitochondrial citrate oxidation by Aspergillus
      niger.
AB  - We have re-assessed the hypothesis that an accumulation of intracellular glycerol
      triggers the accumulation of citric acid by Aspergillus niger by inhibiting the
      activity of the mitochondrial NADP-dependent isocitrate dehydrogenase isoenzyme.
      To this end, we have incubated mycelia of A. niger with 0.5 M glycerol, which
      resulted in a maximal intracellular glycerol pool level of 0.92 M, comparable to
      that determined during the early phase of citrate accumulation. This addition
      affected neither the uptake of [1,5-14C] citrate from the medium nor the rate of
      the subsequent release of 14CO2 by the mycelia, indicating no effect on citrate
      oxidation. Mitochondria isolated from mycelia previously loaded with 0.5 M
      glycerol contained 8% of the total mycelial glycerol. They released 14CO2 from
      exogenously added [1,5-14C]citrate at the same rate as mitochondria isolated from
      mycelia not loaded with 0.5 M glycerol. The addition of glycerol had no effect on
      the activity of the purified NADP-specific isocitrate dehydrogenase, but appeared
      to inhibit the activity in crude cell-free extracts of A. niger. We conclude that
      the intracellular accumulation of glycerol does not affect the rate of
      mitochondrial citrate oxidation and is therefore, in contrast to previous claims,
      not a trigger of citrate accumulation.

PMID- 8885411
TI  - Chorismate synthase from Staphylococcus aureus.
AB  - The aroC gene encoding chorismate synthase and the ndk gene encoding nucleoside
      diphosphate kinase (Ndk) were cloned from Staphylococcus aureus. DNA sequencing
      suggests that aroC is located in an operon with aroB and aroA and encodes a
      protein of 388 amino acids with 61% identity to the aroF gene product of Bacillus
      subtilis. The ndk gene of S. aureus encodes a protein of 149 amino acids which
      exhibits a high degree of identity to other bacterial Ndk proteins. The 3' end of
      the S. aureus gerCC gene was also identified by sequencing and was located
      immediately upstream of ndk. The gerCA and gerCB genes were found to be located
      upstream of gerCC by Southern hybridization analysis. This observed linkage of
      the gerC genes with the ndk, aroC and aroB genes has been similarly observed in
      B. subtilis. The S. aureus chorismate synthase was overexpressed to a high level
      in Escherichia coli using a T7 promoter plasmid construct, the enzyme was
      purified to near homogeneity in two steps and found to be a homotetramer with a
      subunit molecular mass, estimated by electrospray mass spectrometry, of 43024 Da.
      The properties of S. aureus chorismate synthase are compared with those of the B.
      subtilis and E. coli enzymes.

PMID- 8885412
TI  - Proline iminopeptidase gene from Xanthomonas campestris pv. citri.
AB  - The pip gene coding for the proline iminopeptidase (Pip) of Xanthomonas
      campestris pv. citri was cloned in an Escherichia coli leuB strain using a
      selective medium containing the dipeptide D-Ala-L-Leu as the sole source of L
      leucine. Nucleotide sequencing of this gene revealed a 939 bp open reading frame
      encoding a 312 amino acid protein (35 126 Da). The deduced amino acid sequence
      showed 47% identity with the Pip from Neisseria gonorrhoeae. A lacZ-pip fusion
      gene was overexpressed in E. coli under the control of the Plac promoter. The Pip
      of X. campestris hydrolysed L-prolyl-p-nitroanilide with the highest efficiency,
      but was also able to hydrolyse L-alanyl-p-nitroanilide and D-alanyl-p
      nitroanilide. The molecular mass of Pip was found to be 35 kDa by SDS-PAGE and
      120 kDa by gel filtration, suggesting that the active enzyme is a multimer.

PMID- 8885413
TI  - The urea cycle of Helicobacter pylori.
AB  - The presence and activities of the enzymes of the urea cycle in the bacterium
      Helicobacter pylori were investigated employing one- and two-dimensional NMR
      spectroscopy and radioactive tracer analysis. Cell suspensions, lysates and
      membrane preparations generated L-ornithine and ammonium at high rates in
      incubations with L-arginine, indicating the presence of arginase activity.
      Anabolic ornithine transcarbamoylase (OTCase) activity was identified by the
      formation of heat-stable products in incubations of cell-free extracts with
      ornithine and radiolabelled carbamoyl phosphate. The heat-labile product that
      resulted from incubations of cell-free extracts with citrulline radiolabelled in
      the guanidino moiety revealed the presence of catabolic OTCase activity.
      Argininosuccinate formation and catalysis indicated the presence of
      argininosuccinate synthetase and argininosuccinase activities. The findings
      suggested that H. pylori has a urea cycle which acts as an effective mechanism to
      extrude excess nitrogen from cells.

PMID- 8885414
TI  - The thiJ locus and its relation to phosphorylation of hydroxymethylpyrimidine in
      Escherichia coli.
AB  - Extracts from Escherichia coli K-12 contained two distinct enzymes capable of
      catalysing the phosphorylation of hydroxymethylpyrimidine (HMP) to HMP
      monophosphate: pyridoxine kinase (EC 2.7.1.35) and an enzyme that has not
      previously been genetically analysed, HMP kinase (EC 2.7.1.49). Two distinct
      genes, pdxL and thiJ, specify the activities of the former and latter enzymes,
      respectively. The inactivation of both genes by independent mutations in the same
      cell resulted in the complete loss of HMP kinase activity. Experiments with a
      series of strains that carry mutations in thiC, thiC pdxB, thiC pdxB pdxL and
      thiC pdxB pdxL thiJ revealed that the ability of the double mutant (pdxL thiJ) to
      utilize HMP in thiamin pyrophosphate biosynthesis was restored by introducing the
      wild-type allele corresponding to the thiJ mutation. The thiJ locus was mapped on
      the chromosome near the thiD and thiM loci, which govern the activities of
      phosphomethylpyrimidine kinase (EC 2.7.4.7) and hydroxyethylthiazole kinase (EC
      2.7.1.50), respectively.

PMID- 8885415
TI  - Acid tolerance in Listeria monocytogenes: the adaptive acid tolerance response
      (ATR) and growth-phase-dependent acid resistance.
AB  - Listeria monocytogenes acquired increased acid tolerance during exponential
      growth upon exposure to sublethal acid stress, a response designated the acid
      tolerance response (ATR). Maximal acid resistance was seen when the organism was
      exposed to pH 5.0 for 1 h prior to challenge at pH 3.0, although intermediate
      levels of protection were afforded by exposure to pH values ranging from 4.0 to
      6.0. A 60 min adaptive period was required for the development of maximal acid
      tolerance; during this period the level of acid tolerance increased gradually.
      Full expression of the ATR required de novo protein synthesis; chloramphenicol, a
      protein synthesis inhibitor, prevented full induction of acid tolerance. Analysis
      of protein expression during the adaptive period by two-dimensional gel
      electrophoresis revealed a change in the expression of at least 23 proteins
      compared to the non-adapted culture. Eleven proteins showed induced expression
      while 12 were repressed, implying that the ATR is a complex response involving a
      modulation in the expression of a large number of genes. In addition to the
      exponential phase ATR, L.monocytogenes also developed increased acid resistance
      upon entry into the stationary phase; this response appeared to be independent of
      the pH-dependent ATR seen during exponential growth.

PMID- 8885416
TI  - Upstream sequence of the parahydroxyphenyl-pyruvate dioxygenase (melA) coding
      region leading to enhanced expression in Shewanella colwelliana.
AB  - Hyperexpression of the enzyme, parahydroxyphenylpyruvate dioxygenase (pHPPH;
      melA), in the tyrosine degradative pathway yields excess homogentisic acid which
      oxidatively polymerizes to pyomelanin. Depression of melA in Shewanella
      colwelliana strain D was found to result from a single base pair transition
      upstream of the promoter. This was the sole lesion detected in pHPPH
      hyperexpressing strains. It is suggested that a T to C transition alters the mRNA
      structure, exposing the ribosome binding site, thereby enhancing translational
      efficiency.

PMID- 8885417
TI  - Antifungal screening of seven new azole derivatives.
AB  - Two strains of the dermatophyte Epidermophyton floccosum were treated with seven
      new synthetic azole derivatives to determine their possible antifungal activity.
      Among these, two diazopyrazoles (1-phenyl-3-methyl-4-diazo-5-methanesulphonamid
      and 1,3-dimethyl-4-diazo-5-methanesulphonamid) and the triazole (4-methyl-6-t
      butylpyrazolo[3,4-d] [1,2,3]triazole) were inactive at the highest dose tested
      (100 micrograms/ml). The 4-methyl-6-phenyl-pyrazolo[3,4-d] [1,2,3]triazole
      produced only a partial inhibition of growth, whereas the most active compounds
      were the two thiadiazines (6H-3-phenyl-5-methyl-7-(3,4
      dichlorophenyl)pyrazolo[3,4-c] [1,2,5]thiadiazine-2,2-dioxide and 7-methyl-2
      phenyl-4H-pyrazolo[1,5-c] [1,3,5]thiadiazine-4-one), and an aminoisoxazole (3
      methyl-5-aminoisoxazole-4-thiocyanate), which induced a remarkable and sometimes
      complete reduction in the growth rate of the fungus. The structure-activity
      relationships are discussed.

PMID- 8885418
TI  - Analyzing sequencing reactions from bacteriophage M13 by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - The current demand for improved DNA sequencing methodologies posed by the Human
      Genome Project has spurred the investigation of alternatives to gel
      electrophoresis. Matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry has great potential for the rapid analysis of DNA fragments. Mock
      Sanger sequencing mixtures have been successfully analyzed by MALDI by pooling
      synthesized oligonucleotides corresponding to the M13 bacteriophage sequence.
      More recently, analyses of Sanger sequencing fragments enzymatically generated
      from synthetic templates of 45 or 50 bases were reported. In the present study,
      these feasibility demonstrations are extended to show MALDI sequencing from the
      M13 bacteriophage DNA template commonly used in actual Sanger sequencing. The
      results show sequence determination for extension products up to 35 bases in
      length. Different desalting and purification procedures were investigated and it
      was found that salt could be efficiently reduced by removal of the template in a
      post-reaction step. Work in progress to stabilize DNA by chemical modification,
      employed in conjunction with the methods described here, should enable
      significant extension of the length of readable sequence.

PMID- 8885419
TI  - Confirmation of gentian violet and its metabolite leucogentian violet in catfish
      muscle using liquid chromatography combined with atmospheric pressure ionization
      mass spectrometry.
AB  - Gentian violet (GV) is a triphenylmethane dye antiseptic with potential for
      illegal use in livestock production, especially aquaculture where the related
      malachite green has been widely used. This potential misuse has regulatory
      importance because of the observed rodent carcinogenicity of GV. This report
      describes the use of online LC-APCI/MS for confirmation of incurred GV residues,
      and those of its principal metabolite, LGV, in catfish muscle following treatment
      of live catfish with GV under putative use conditions. LC with APCI/MS detection
      provided sensitive analysis of GV and LGV with estimated detection limits of < 1
      pg observed for both compounds. Fragmentation of GV and LGV via in-source CID was
      effected by varying the sampling cone-skimmer voltage. Ion intensity data were
      collected using a rapid cone voltage switching procedure that permits selected
      ion acquisition under optimal conditions for the parent molecule and several
      selected fragment ions. For GV, four ions including the ionized molecule were
      used and for LGV, six ions including the protonated molecule were used. The
      levels of GV and LGV in muscle from fish dosed with 10 micrograms/l in aquarium
      water were determined by LC/VIS to be 0.5 and 44 ppb, respectively. Analysis of
      these samples yielded ion intensity ratios that agreed precisely between
      injections (< 5%) and accurately with those generated by a comparable amount of
      authentic GV and LGV (< 10% deviation). These results show the utility of on-line
      LC-APCI/MS to do both sensitive confirmatory analyses of incurred drug residues
      for use in monitoring the food supply.

PMID- 8885420
TI  - Sulfamethazine, sulfothiazole and albendazole residue dosage in food products
      determined by liquid chromatography/tandem mass spectrometry.
AB  - There is a growing demand for analytical techniques for the detection of a wide
      variety of residues from synthetic molecules in matrices such as soil, water, air
      and food. These techniques have to meet the requirements of speed and sensitivity
      as well as the ability to handle any matrix with minimal sample clean-up.
      Features of mass spectrometry combined with liquid chromatography can fulfill
      these requirements as is shown by this work which reports the use of ion spray
      ionization coupled with tandem mass spectrometry for the detection of some drug
      residues. In particular, the direct use of existing LC methods, originally
      conceived for use with some other sort of detector, is demonstrated.

PMID- 8885421
TI  - The in vitro glycation of lysozyme and the influence of buffer concentration
      investigated by mass spectrometry.
AB  - The non-enzymatic reactions between glucose or fructose with lysozyme, performed
      under pseudo-physiological conditions, have been studied by means of matrix
      assisted laser desorption/ionization mass spectrometry. Phosphate buffer at
      concentrations of 0.05, 0.2 and 0.5 M has been employed. The formation of
      glycated proteins as well as of cross-linking products has been always observed.
      In the case of glucose, high phosphate buffer concentrations affect the glycation
      kinetics and promote the formation of cross-linking products. With fructose, such
      influence is moderate, the reaction kinetics being mainly influenced by the
      higher reactivity of the sugar.

PMID- 8885422
TI  - Radioactivity in two tide-washed marsh areas in the eastern Irish Sea: a
      radiological assessment.
AB  - The doses received by man from exposure to artificial radionuclides deposited
      onto marsh land during tidal inundation on the English side of the Solway Firth
      and the Dee Estuary have been assessed. The range of total doses received by the
      different marsh user groups was similar in both study areas, varying from < 1
      microSv year-1 to approximately 55 microSv year-1, with total dose dominated by
      the contribution from external exposure (generally 80% of the total). The maximum
      doses in both study areas were received by people working on the marshes and are
      well below the annual dose limit recommended by ICRP for members of the public (1
      mSv year-1). The largest dose estimated (56 microSv year-1) is only 6% of the
      recommended dose limit.

PMID- 8885423
TI  - Genetic effects of contaminant exposure--towards an assessment of impacts on
      animal populations.
AB  - This review aims both to identify the potential risks to animal populations as a
      consequence of exposure to genotoxins and to identify the techniques most useful
      in assessing these risks. These evaluations are complicated by the fact that
      contaminant exposure acts both to restructure naturally occurring genetic
      diversity and, when contaminants have mutagenic activity, to enhance the rate of
      introduction of new variation. There is now evidence that contaminant exposure
      often leads to change in the genetic attributes of natural populations. Short
      lived organisms often develop resistance to contaminants, with only modest
      impacts on diversity in the balance of the genome, although massive mortality
      occurs during the gene replacement. Resistance is, however, less likely to evolve
      in species with small population size, such as many wildlife species. Such
      species will experience population declines or extinction as the impact of
      contaminants on physiological systems is not counteracted by gene replacements.
      Even when adaptation to exposure occurs, populations may suffer diminished
      fitness as a consequence of the mutagenic effects of contaminants. The expression
      of these effects range from an increase in the incidence of developmental
      abnormalities to shifts in chromosomal and gene structure. The assessment of this
      broad range of impacts can only be accomplished with a spectrum of analytical
      approaches. However, recent advances in molecular and developmental genetics are
      now making possible the detailed assessment of these mutagenic impacts in natural
      populations.

PMID- 8885424
TI  - Monitoring of fish and human exposure to mercury due to gold mining in the Lake
      Victoria goldfields, Tanzania.
AB  - Monitoring of environmental and human exposure to mercury in the Nungwe Bay area
      of the Lake Victoria goldfields, Tanzania, has revealed low mercury
      concentrations in fish (range: 1.8-16.9 ppb, mean: 7.0 ppb) and human hair
      (range: 156-5433 ppb, mean: 947 ppb) that represent background levels. Gold
      mining has not produced a significant increase in environmental methylmercury
      that is available for bioaccummulation in aquatic food chains. Urinary mercury
      levels in gold mine workers frequently exposed to Hg vapour in amalgamation and
      burning of amalgam were significantly higher (mean: 241 ng/ml) than those in the
      general mine population not occupational exposed to Hg (mean: 2.6 ng/ml).
      Rotation of mine duties reduced Hg exposure levels and hence the risk of
      intoxication in the gold mine workers. The lowest urinary and hair mercury levels
      were found in the Nungwe Bay fishing village population. This was consistent with
      the low mercury content of fish consumed by the inhabitants of the Nungwe Bay.

PMID- 8885425
TI  - Atmospheric lead pollution in KwaZulu/Natal, South Africa.
AB  - Average atmospheric concentrations of lead were found to be 1.8, 0.86, 0.56 and
      0.44 microgram m-3 in industrial, commercial, park/beach and residential areas of
      Durban. Exposure to these elevated levels would represent a health hazard to many
      children in the city. Lower lead concentrations were found in a local township
      (0.26 microgram m-3) and rural (0.03 microgram m-3) areas of Natal Province. The
      study provided background data that can be used to follow the trajectory of
      change in atmospheric lead levels now that lead-free gasoline has been introduced
      into the country.

PMID- 8885426
TI  - Estimation of dietary intake of arsenic in the general population of the Republic
      of Croatia.
AB  - Total amounts of arsenic in foods sold in Croatia were determined over a 5-year
      period (1988-1993). Highest mean levels were recorded in the following food
      groups: fish (498 micrograms/kg), fishery products (270 micrograms/kg) and cheese
      and dairy products (39 micrograms/kg); lowest levels were contained in fruit,
      chocolate and fruit products (0.2, 0.2 and 0.3 microgram/kg, respectively). Mean
      weekly dietary arsenic intake estimated on the basis of the level of arsenic and
      consumption of the studied foodstuffs is 81.9 micrograms/individual. The PTWI
      level achieved by the general population of Croatia is 7.8%.

PMID- 8885427
TI  - Temporal changes in concentration of radiocaesium in lake sediment and fish of
      southern Finland as related to environmental factors.
AB  - In 1992 the concentration of radiocaesium in the surface layer of bottom sediment
      of 52 lakes of southern Finland was found to have declined on average to 27.4% of
      1987-88 levels and to 25.7, 28.0 and 38.6% of 1988 levels in the tissues of
      perch, pike and roach, respectively. The sediment radiocaesium concentration was
      higher in larger lakes and in lakes having a large catchment, but lower in
      oligotrophic than eutrophic lakes, when the total amount of electrolytes and
      organic matter was high. The concentration of radiocaesium in perch and pike was
      lower in eutrophic than oligotrophic lakes and lower in all three fish species
      when the concentration of electrolytes was high. Lower radiocaesium values in
      both sediments and fish of eutrophic when compared with oligotrophic lakes may be
      due to a greater dilution of this contaminant into a higher biomass. Water colour
      and pH were negatively correlated with radiocaesium in perch only. A lower
      radiocaesium level in perch in humic water lakes may be due to an adsorption of
      radiocaesium onto humus particles which reduces its bioavailability and transfer
      along the food chain. Radiocaesium in fish and in sediment were positively
      correlated with each other for perch and roach whose diets comprise mainly the
      detritivore or sediment feeding bottom animals. In perch the radiocaesium
      concentration was high when the water retention time of the lake was long. A
      tropic level bioconcentration was evident in the threefold higher radiocaesium
      level in predatory pike compared with roach. The decline in radiocaesium was most
      pronounced in sediment when the catchment area was large, when the water pH was
      high and when the sediment surface contained a low proportion of organic matter.
      In fish the largest decline in radiocaesium was recorded in pike from eutrophic
      or shallow lakes and when the lake water retention time was short. In perch and
      roach the reduced radiocaesium levels were not due to effects of water quality or
      lake morphometrical properties. Two different sediment core samplers, a Kajak
      corer and a Limnos corer, gave comparable results.

PMID- 8885428
TI  - Preliminary data on hard metal workers exposure to tungsten oxide fibres.
AB  - The first personal exposure data for tungsten oxide fibres, in two hard metal
      manufacturing industries is presented. Occupational exposure was studied by
      static and personal measurements during tungsten metal production. Three
      different initial materials were used, ammonium-paratungstate (APT), blue oxide
      and tungsten trioxide. In both factories, airborne tungsten oxide fibres were
      detected both in static and personal samples. Fibre exposure varies for different
      activities. Charging of raw material, changing the hammer, cleaning-work on the
      cyclone and the micro-filter were found to be among the most high dusty
      operations. However, as workers use respirators during cleaning operations, these
      filters could not be related to personal exposure. The calcination of APT to the
      blue oxide generates fibrous dust. The raw material imported as blue oxide is
      also fibrous material and both charging it into the calcination furnace and re
      charging it into the reduction furnace generates unnecessarily additional dusty
      periods. A single reduction-stage is, therefore, preferable. Furthermore, the
      tungsten trioxide raw material is non-fibrous, therefore, calcination of APT to
      tungsten trioxide and its reduction to tungsten metal is preferable with respect
      to minimising workers exposure to tungsten oxide fibres.

PMID- 8885429
TI  - Lead content of rice collected from various areas in the world.
AB  - Rice samples consumed by local populations were collected between 1990 and 1995
      in 17 areas in the world, mostly from Asia (10 areas), but also from 7 areas
      outside of Asia. In total, 1528 samples were obtained (about one half from Japan)
      and were analyzed for lead (Pb) by electrothermal atomic absorption spectrometry.
      When the Pb contents in rice samples were classified into 10 areas in Asia, the
      highest and the lowest geometric means (GMs) were for Indonesia (38 ng/g) and
      Australia (2 ng/g), respectively. Among 7 regions outside Asia, the GM was
      highest for Spain (58 ng/g) and the lowest for the USA. (3 ng/g). Moreover, inter
      regional differences were significant, when more than 100 samples from one area
      were divided into 3-9 regions and GMs for regions were compared. There was a
      marked difference in Pb contents in rice by areas and regions in the world.
      Nevertheless, comparison by area of the present results with those reported in
      literature show that there has been no substantial reduction in Pb in rice in the
      past decade either in Japan or elsewhere in the world.

PMID- 8885431
TI  - Toward versatile international co-operation in circumpolar health.

PMID- 8885430
TI  - Fluoride in drinking water and human urine in northern and central Poland.
AB  - The fluoride concentration in drinking water and in urine of the inhabitants of
      94 localities in Northern and Central Poland was determined. The analyses were
      performed potentiometrically using a fluoride-specific electrode. In most of the
      localities the fluoride concentration in water was < 0.3 mg/l, which is far below
      the recommended level for caries control. In these communities fluoridation of
      water is advised. In six localities the water fluoride concentration was 1.2
      mg/l. The elevated water fluoride is of natural (Malbork) as well as of
      anthropogenic (Wislinka) origin. The mean fluoride level in the urine in the
      investigated localities was 1.10 mg/l (range 0.10-2.67 mg/l). No significant
      correlation between the concentration of fluoride in drinking water and human
      urine was found in this study. This suggests that the elevated fluoride level in
      urine may be caused not only by the water fluoride, but also by the inhalation of
      dust particles containing fluoride, and by the diet.

PMID- 8885432
TI  - A meta-analytical approach to the pooling of blood pressure values in children.
AB  - Meta-analysis of blood pressure (BP) studies in children was performed in order
      to evaluate whether BP readings obtained in various studies may be pooled. In
      total 30 original reports on BP in children were analyzed and the age and sex
      specific BP values reported for 12 and 15-year-old subjects in 11 of these were
      tested for homogeneity. The differences in sample size-weighted means between the
      devices used (with 95% confidence intervals) were evaluated. The BP values
      reported in different studies for systolic Korotkoffs first phase BP (K1) and
      diastolic Korotkoffs fourth (K4) and fifth (K5) phase BP were shown to be too
      heterogeneous (p < 0.001) to be pooled. Heterogeneity and measurement biases in
      the BP results were caused by differences between the devices and the diastolic
      BP indicator (K4 vs K5) and by observer biases such as uncontrolled terminal
      digit preference. The device-specific weighted means for K1, K4 and K5 BP in 12
      and 15-year-old subjects showed statistically significant differences between
      random zero (RZS) and ordinary mercury (OMS) sphygmomanometer (p < 0.001) the
      difference (OMS-RZS) being from 0.7 to 6.6 mmHg for K1 (p < 0.001, except in 12
      year-old girls), from 1.1 to 7.1 mmHg for K4 (p < 0.001, except in 12-year-old
      girls) and from 4.5 to 7.9 mmHg for K5 (p < 0.001). Such a discrepancy was also
      apparent between ordinary and automated mercury sphygmomanometer (AMS) in the
      case of diastolic K4 and K5 BP (p < 0.001), but not in K1. BP results obtained in
      different investigations using different BP devices and Korotkoffs phases as
      indicator of diastolic BP should not be pooled. More widely accepted
      recommendations are needed to standardize the measurement of BP in children.

PMID- 8885433
TI  - Seasonal cutaneous immune responses in an Antarctic wintering group: no
      association with testosterone, vitamin D metabolite or anxiety score.
AB  - Immune function is modulated by a complex set of neuroendocrine factors including
      sex hormones, vitamin D metabolites and stress. Antarctic expeditioners exhibit
      reduced cell mediated immunity. Studies have also shown a reduction in
      testosterone levels in wintering expeditioners and suggested a correlation
      between levels of anxiety and reduced immune function in brief trip
      expeditioners. Nineteen male Antarctic expeditioners were followed by 3 monthly
      assessments of cell mediated immunity, levels of testosterone and vitamin D
      metabolite and psychological indicators of anxiety. There was a significant
      reduction in immune function during the study period, consistent with previous
      Antarctic studies. Levels of testosterone, anxiety and the immunoregulatory
      metabolite of vitamin D did not alter significantly. In this group the reduction
      in immune function did not show a correlation with levels of anxiety or the
      hormones studied.

PMID- 8885434
TI  - Detection of alpha-fetoprotein and hepatitis-B surface antigen in blood spotted
      on filter paper: use as a screen for hepatocellular carcinoma in Alaska Natives.
AB  - A program of twice yearly testing of Alaska Native carriers of hepatitis-B
      surface antigen (HBsAg), for alpha-fetoprotein elevations as an indicator of
      early hepatocellular carcinoma has been established in Alaska. Because many HBsAg
      carriers live in remote regions of Alaska, logistical and cost considerations
      complicate the efficiency of this program. We evaluated the feasibility of using
      blood spotted onto mail-in cards as a system of blood collection and commercial
      assays for alpha-fetoprotein and HBsAg testing. We compared alpha-fetoprotein
      levels and the detection of HBsAg in both plasma and blood spots from HBsAg
      positive carriers, normal volunteers, and pregnant females. There was good
      correlation between serum and blood spot AFP levels (r = 0.94, p < 0.001) over a
      wide range of serum alpha-fetoprotein levels. alpha-fetoprotein and HBsAg
      remained detectable in blood spots stored at room temperature for more than 8
      weeks. The sensitivity of detection of HBsAg in blood spots was not as great in
      blood spots when compared to plasma levels. This system has been incorporated
      into the hepatocellular carcinoma screening program in Alaska. It should also
      prove feasible and economical for such screening to be undertaken in developed
      countries and possibly make alpha-fetoprotein screening affordable in those
      developing countries where the prevalence of hepatitis-B virus infection is high.

PMID- 8885435
TI  - A case-control study of cancer risk factors in the Alaskan Arctic: responding to
      village concern about environmental radiation.
AB  - In response to community concern and documented excessive recent cancer incidence
      in the Alaskan arctic village of Point Hope and despite the small population
      size, a case-control study was undertaken to help gain clues as to the cause of
      cancer in this remote village. Residents diagnosed with cancer from 1969 to 1994,
      who could be interviewed concerning cancer risk factors, were matched with
      resident controls. Residence in Point Hope in 1962 (odds ratio = 17.31, 95%
      confidence limits = [1.69, 179.4]) was the only significant cancer risk factor
      detected. All other risk factors related to the environment, diet, occupation,
      family and social history were unremarkable. Residence in this village over 30
      years ago may be a key link to the cause of cancer in Point Hope.

PMID- 8885436
TI  - Substance use, mental health, and health in Alaska: emphasis on Alaska Native
      peoples.
AB  - It has always been a problem in Alaska to obtain a compilation of accurate and
      current data with regard to mental health, health, and substance abuse. This
      paper was designed to pull together different sources of data to present a
      comprehensive perspective on the substance use, mental health, and health
      problems facing Alaskans today. The article summarizes the most current substance
      abuse, mental health, and health data available for the State of Alaska from
      public, academic, and institutional sources. It emphasizes data relevant to
      Alaska Native groups, calling for improved efforts in the future to collect data
      according to ethnicity and gender. The data presented identify a number of
      significant substance use and mental health problems that are prevalent in
      Alaska, providing geographic and ethnic data wherever available.

PMID- 8885437
TI  - Attitude towards the future of the environment among medical students in the
      University of Oulu.

PMID- 8885438
TI  - Presentation of Federico Hernandez Morales, MD, MACP. 1994 laureate of the Puerto
      Rico Chapter American College of Physicians.

PMID- 8885439
TI  - A descriptive-exploratory study of outcome and some biopsychosocial
      characteristics of drug dependent veterans in Puerto Rico.
AB  - OBJECTIVE: The authors attempted to correlate outcomes with various significant
      biopsychosocial variables in drug dependent veterans receiving outpatient
      treatment at San Juan V.A.M.C. METHODS: The clinical charts of 120 inactive
      patients were examined using a 50 item questionnaire. The data was processed and
      analyzed using the EpiInfo v.5 computer program. The outcome of the patients was
      measured using a Goal Attainment Scale Technique with demonstrated validity and
      reliability. RESULTS: The patients retention in treatment for 12 or more visits
      and its relationship to good outcomes was the most significant finding of this
      study (P < 0.00000000, 80.5% of patients improved). Only 5% of patients with 3 or
      less visits showed positive outcomes. Another variable associated with good
      outcomes was a supportive wife (P < 0.02). HIV reactivity was strongly correlated
      with IV drug use (P < 0.037). CONCLUSIONS: The strong correlation of the
      retention of patients in treatment for 12 or more visits and good outcomes should
      alert clinicians and policy makers as to the importance of available and
      effective treatments in the fight against substance abuse and mental health
      problems. This study also showed that a supportive family member is usually the
      best social asset that patients and therapists have in their fight for sobriety.

PMID- 8885440
TI  - Trichobezoar in a 11-year old girl: a case report.
AB  - Bezoars are masses of solidified organic or nonbiological material commonly found
      in the stomach and small bowel. Identification, therapy, and long-term management
      of patients with bezoars depends on accurate classification and knowledge on the
      pathophysiology of formation. Four types of bezoars have been described based on
      their composition: phytobezoars, trichobezoars, lactobezoars, and miscellaneous.
      Pediatric trichobezoars are associated to emotional disturbed children with
      aberrant appetite (trichophagia). Hair strands become retained and attached in
      the folds of the gastric mucosa because the friction surface is insufficient for
      propulsion by peristalsis. They generally are asymptomatic until enlargement
      produce pain, compression or intestinal obstruction. Bezoars are diagnosed with
      conventional radiology and gastroscopy permits identification of its nature.
      Currently, management of bezoars consists of: dissolution, suction, lavage,
      mechanical endoscopic fragmentation using pulsating jet of water, fragmentation
      with extracorporeal shock wave lithotripsy and surgical removal. Treatment should
      also focus on prevention of recurrence, since elimination of the mass will not
      alter the conditions contributing to their formation.

PMID- 8885441
TI  - Etiology and outcome of non-estrogen associated hyperthyroxinemia in euthyroid
      patients at the San Juan City Hospital.
AB  - INTRODUCTION: Hyperthyroxinemia does not always equate to hyperthyroidism.
      Laboratory tests should always be correlated with the clinical picture. A
      mismatch should make one doubt true hyperthyroidism. The purpose of our study was
      to assess the etiology of euthyroid hyperthyroxinemia not associated with
      estrogen use or pregnancy and to review the outcome of those erroneously treated.
      METHODS: The medical records of thirteen euthyroid patients with non estrogen
      associated hyperthyroxinemia were reviewed. They had a complete set of thyroid
      function tests including free T3 and free T4 by membrane dialysis, TRH
      stimulation test and thyroid hormone binding panel. RESULTS: Two diagnostic
      groups were identified: Hyperthyroxinemia secondary to binding abnormalities
      (7/13), better known as familial dysalbuminemic hyperthyroxinemia (FDH) and
      hyperthyroxinemia secondary to Thyroid Hormone Resistance (THR) (6/13). The FDH
      group had an elevated T4 and FTI, with normal T3RU, TSH, TRH stimulation test but
      an abnormal thyroid hormone binding panel which was used to confirm the
      diagnosis. The THR group had two laboratory presentations: Four patients
      presented with all the thyroid hormone tests elevated (T4, T3, T3RU, FTI)
      including a free T3 and free T4 by membrane dialysis with a normal TSH and TRH
      stimulation test and a normal T4 binding panel. This presentation is typical for
      a TRH patient with a nuclear receptor defect where all the precursos to the
      defect accumulate. Two patients with THR presented elevated T4 and free T4 but
      normal T3 and free T3, localizing the defect at the level of the active T4
      transport mechanism across the cellular membrane. These two patients had a normal
      TSH, TRH stimulation test and T4 binding panel. Two patients were treated
      erroneously with radioactive iodine and became extremely hypothyroid in spite of
      normal TFTs. Very high dose of thyroid hormone replacement were required to
      restore euthyroidism. CONCLUSION: One must suspect these two entities in patients
      clinically euthyroid who have elevated T4 but non-suppressed TSH. A normal TSH
      and TRH test confirm euthyroidism. A thyroid hormone binding panel differentiates
      FDH from THR. Neither group require treatment. If treated erroneously and T4
      drops to normal values, one must again induce hyperthyroxinemia to restore
      euthyroidism in these patients.

PMID- 8885442
TI  - Epidermoid carcinoma of the hand: report of a case.
AB  - The case of a 71 year old man who presented with an advanced epidermoid carcinoma
      of the dorsum of the hand, is reported. The patient was treated with radiotherapy
      as an alternative to amputation. Irradiation consisted of a combination of Co-60
      photons and 6 Mev electrons. The cosmetic and functional results were excellent
      and the patient has been free of hand tumor for two and one-half years.

PMID- 8885443
TI  - Infections caused by parvovirus B19.
AB  - Parvovirus B19 was discovered in 1974 by Cossart et al; is a single stranded
      unenveloped DNA virus, which virion is isometric, uniform and has icosagedral
      symmetry. B19 infection has been found in all countries, it is almost certainly
      world-wide in distribution. Infections occurs most frequently in late winter,
      spring and early summer months and are transmitted by respiratory route. Erythema
      infectiosum is the most common manifestation of human parvovirus B19 infection,
      is most commonly acquired between 4 and 10 years of age and at least 60% of
      adults are seropositive. Erythema Infectiosum is characterized by three stages of
      rash that involves the face and may also involves trunk and extremities. In adult
      patients, particularly women, arthralgia or arthritis have been associated with
      up to 80% of Erythema Infectiosum casually starts in the small joints of the
      hand. Maternal parvovirus B19 infection with or without rash, can affect fetus.
      Transient aplastic crisis can be caused by HPV B19 in patient who have increased
      rate of RBC destruction or loss. Others diseases or symptoms complexes may be
      associated with B19 infection in the coming years as this virus and its
      infections continues being an interesting field of investigation.

PMID- 8885444
TI  - NHS or private--a balanced choice.

PMID- 8885445
TI  - Spending quality time with Andrew Shephard. Interview by Diane Ashmore.

PMID- 8885446
TI  - Withdrawal of funding for intercalating BSc students.

PMID- 8885447
TI  - General anaesthesia.

PMID- 8885448
TI  - Mike Bassett talks to the editor.

PMID- 8885449
TI  - Evidence based assessment.

PMID- 8885450
TI  - Dental therapists.

PMID- 8885451
TI  - Marketing dentistry.

PMID- 8885452
TI  - A survey of general anaesthesia, sedation and resuscitation in general dental
      practice.
AB  - The Poswillo Report, published in 1990, made recommendations regarding general
      anaesthesia (GA), sedation and resuscitation in dentistry. The aims of the
      present study were to examine the level of provision of GA and sedation by
      general dental practitioners (GDPs) a few years after the publication of the
      report, and to estimate the degree of compliance of GDPs with a number of its
      principal recommendations. In May 1994, a questionnaire was sent to 268 GDPs in
      two Scottish Health Boards, and a response rate of 80% was achieved. Thirteen per
      cent of respondents had treated GA cases during 1993-94 while 18% indicated that
      they had stopped providing a GA service since the immediate pre-Poswillo years.
      However, 91% had referred some patients elsewhere for treatment under GA. There
      was very little evidence of a replacement of GA by sedative techniques. The
      percentages of respondents using inhalation or intravenous sedation during the
      previous year were 9% and 27%, respectively. Almost all of the respondents
      reported that they had been trained in cardiopulmonary resuscitation and 60%
      stated that resuscitation exercises were practised at least once a year. While
      over 80% of the practitioners indicated that their dental surgeries stocked the
      emergency drugs recommended in the Poswillo Report, 12% expressed concern
      regarding the length and content of the drug list.

PMID- 8885453
TI  - Cognitive-behavioural therapy for idiopathic burning mouth syndrome: a report of
      two cases.
AB  - Two cases of burning mouth syndrome (BMS) that were successfully managed with
      cognitive-behaviour therapy (CBT) are reported. The principles and application of
      CBT are described. The cases presented demonstrate the important role that this
      type of psychological approach can have in the management of patients with BMS.

PMID- 8885454
TI  - Nystatin pastilles and suspension in the treatment of oral candidosis.
AB  - Clinical audit revealed that the treatment of oral candidosis was more successful
      with nystatin pastilles than with nystatin suspension. The purpose of this
      investigation was to determine the reasons for this observation. The
      concentration of nystatin needed to kill 49 consecutive clinical isolates of
      Candida albicans was measured. The isolates varied in cidal concentrations from
      1.875 to 30 U/ml. The time taken to kill these isolates at their cidal
      concentrations was found to vary from 120 to 300 min. Volunteer studies showed
      that antifungal activity in the oral cavity was eliminated rapidly after the use
      of nystatin suspension. In contrast, the polyene could be detected for at least 5
      hours after use of the nystatin pastille. The nystatin pastille can be expected
      to be more effective at killing Candida albicans than the suspension due to its
      persistent effects.

PMID- 8885455
TI  - Transmigration of permanent mandibular canines.
AB  - Transmigration is a rare occurrence relating to the movement of a mandibular
      canine across the mid-line of the mandible. Two cases are presented where
      patients referred for assessment of third molar problems subsequently revealed on
      radiological examination the asymptomatic phenomenon of transmigration. With
      dental panoramic radiography becoming more widespread among dental practitioners
      it is possible that more cases of transmigration will be observed.

PMID- 8885456
TI  - Practical marketing for dentistry. 9. Marketing communication tools.
AB  - There are many communication tools available at a wide range of different costs.
      This article discusses a selection of the tools available and also examines the
      most important first step-identifying your target audience.

PMID- 8885457
TI  - Treating restorative dentistry to health.
AB  - The concepts that underpin much of dental practice need refocusing so as to
      accommodate the many scientific advances that have been made in recent years in
      understanding oral disease processes and their management. "Treatment' should
      come to mean what it says, namely the curing of diseases- and much of this can
      only be accomplished by non-invasive means. Restorative procedures should be seen
      simply as prosthetic, making up for lost tissues. The sequence of events with
      respect to caries should usually be diagnosis followed by treatment, and then the
      option of restoration if appropriate. In order to achieve this state of affairs
      for the whole population, I believe it will be necessary to stream dental
      undergraduates so that, while a portion learn restorative techniques and become
      licensed to practise them, the remainder concentrate on the non-restorative
      aspects of dentistry, having a special emphasis on the prevention and non
      invasive "treatment' of oral and dental diseases, including caries, on a
      community scale. This latter group of dentists would not be licensed to undertake
      restorative procedures.

PMID- 8885458
TI  - Centenary year of scientific papers in the British Dental Journal.
AB  - In this paper Professor Fleming describes several aspects of antiseptics. He
      begins by considering the influence of the medium on the antiseptic, and of far
      more relevance, the speed of disappearance of the antiseptic. He then describes
      the ineffectiveness of an antiseptic in sterilising and treating a septic wound,
      backing up his remarks with experimental evidence. His lecture then looks at the
      effect of chemical antiseptics on the body's normal protective mechanism,
      specifically how some antiseptics inhibit the antibacterial effect of protective
      fluids (such as saliva and tears) as well as the antibacterial action of
      leucocytes. At the conclusion of the lecture he mentions specificity, and
      prophetically remarks on how penicillin may be used in the future in the
      treatment of septic wounds.

PMID- 8885459
TI  - Bovine spongiform encephalopathy--too early to relax.

PMID- 8885460
TI  - Medetomidine, alpha 2 adrenoceptors and small animal practice.

PMID- 8885461
TI  - Diagnostic aids and prognostic indicators for chronic grass sickness:
      possibilities for the future.

PMID- 8885462
TI  - Bovine spongiform encephalopathy--the beginning of the end?
AB  - The incidence of bovine spongiform encephalopathy (BSE) in the United Kingdom is
      now declining at a significant rate, indicating that the 1988 ban on feeding
      ruminant-derived meat and bone meal to cattle is having the anticipated effect.
      The question now is whether or not BSE can be completely eradicated. At present
      there is no evidence of lateral or maternal transmission, the occurrence of which
      would complicate the eradication process. Eradication therefore seems to be
      achievable, especially now that meat and bone meal has been recently banned from
      the diets of all farmed animals in the UK. In this review the aetiological role
      of meat and bone meal in the causation of BSE is discussed together with the
      epidemiological data and the results of studies on genetic susceptibility. The
      controversial theories relating to the nature of the causal agent, and strain
      typing studies on BSE agent, are described. Current information on pathogenesis
      and diagnosis is presented. The occurrence of BSE in cattle outside the United
      Kingdom, and BSE-related disease in species other than cattle is also discussed.

PMID- 8885463
TI  - Medetomidine sedation in dogs and cats: a review of its pharmacology, antagonism
      and dose.
AB  - Medetomidine is a relatively new sedative analgesic in dogs and cats but some
      precautions are required when using it. It is a potent alpha 2-adrenoceptor
      agonist and stimulates receptors centrally to produce dose-dependent sedation and
      analgesia and receptors centrally and peripherally to cause marked bradycardia
      and decrease the cardiac output. While hypotension occurs frequently, higher
      doses of the sedative can raise the blood pressure due to an affect on peripheral
      receptors. Slowing of the respiratory rate is a frequent effect of medetomidine
      with some dogs showing signs of cyanosis. Other actions that follow medetomidine
      use are slowing of gastrointestinal motility, hypothermia, changes to endocrine
      function and, occasionally, vomiting and muscle twitching. The clinical use of
      medetomidine in dogs and cats is discussed. Recommended dose rates are presented
      along with precautions that should be taken when it is used alone for sedation,
      as an anaesthetic premedicant or in combination with ketamine, propofol or
      opioids. Hypoxaemia occurs frequently in dogs given medetomidine and propofol.
      The actions of medetomidine can be rapidly reversed with the specific alpha 2
      adrenoceptor antagonist, atipamezole, which is an advantage because undesirable
      and sedative actions of medetomidine can be terminated.

PMID- 8885464
TI  - An evaluation of the use of cisapride in horses with chronic grass sickness
      (equine dysautonomia)
AB  - A clinical trial was carried out to determine the effect of cisapride on rate of
      passage of digesta and clinical parameters in horses with chronic grass sickness.
      Sixteen horses were given intramuscular cisapride (0.1 mg kg-1 three times daily)
      (group I), and 15 received oral cisapride (0.8 mg kg-1 three times daily) (group
      O). A liquid-phase marker (cobalt-EDTA) and a solid-phase marker (polystyrene
      pellets) were given by stomach tube at the beginning of each of three consecutive
      7 day periods, i.e., before, during and after cisapride therapy. Seven horses in
      each group completed the rate of passage trial; the remainder provided clinical
      data only. The rate of passage was found to be significantly faster after
      cisapride therapy than before. Comparison with data from 20 normal animals showed
      a trend towards normal rates of passage after therapy. In cases that died during
      the trial, the caecum and large colon were the main sites of pellet retention.
      Dry matter intake was significantly higher after therapy than before in group O
      and dry matter output was higher after treatment than before in both groups. Gut
      auscultation score increased in both groups in the periods during and after
      cisapride administration but heart rate was unaffected. Diarrhoea and colic
      occurred in each group but its occurrence was not associated with cisapride
      therapy. The results suggest that by increasing gut motility, cisapride is of
      benefit in the management of selected cases of chronic grass sickness.

PMID- 8885465
TI  - Pharmacokinetics of amoxicillin/clavulanic acid combination and of both drugs
      alone after intravenous administration to goats.
AB  - The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination (25
      mg kg-1), and both drugs alone (amoxicillin 20 mg kg-1), clavulanic acid 5 mg kg
      1), was studied after intravenous (i.v.) administration of single doses of 10
      goats. The objective was to determine whether there were differences in the
      plasma kinetics of these drugs when administered in combination or alone. The
      plasma concentration-time data were analysed by compartmental pharmacokinetics
      and non-compartmental methods. The disposition curves for both drugs alone and in
      combination were best described by a biexponential equation (two-compartment open
      model). The elimination half-lives of amoxicillin were 1.05 +/- 0.09 h alone and
      1.13 +/- 0.19 h in combination, and those of clavulanic acid were 0.87 +/- 0.07 h
      and 0.85 +/- 0.09 h, respectively. The apparent volumes of distribution of
      amoxicillin and clavulanic acid were similar in the two treatments. Body
      clearances of amoxicillin were 0.12 +/- 0.01 l h-1.kg alone and 0.11 +/- 0.01 l h
      1.kg in combination, and of clavulanic acid were 0.12 +/- 0.02 l h-1.kg alone and
      0.12 +/- 0.01 l h-1.kg in combination with amoxicillin. The half-lives and body
      clearances of amoxicillin and clavulanic acid did not differ significantly when
      administered alone and in combination. It was concluded that the i.v.
      administration of amoxicillin and clavulanic acid as a combination product did
      not alter the disposition kinetics of either drug.

PMID- 8885466
TI  - Development of a diagnostic DNA probe to detect Setaria digitata: the causative
      parasite of cerebrospinal nematodiasis in goats, sheep and horses.
AB  - Two repetitive sequences (IpSdM and IpSdS) have been cloned and sequenced from
      the genome of Setaria digitata. When IpSdM (214 bp) and IpSdS (201 bp) were
      aligned, a high degree of homology (85%) was observed, indicating that they
      belong to the same family of repeats. IpSdM represents a complete repeating
      element while IpSdS consists of two partial repeating elements arranged in
      tandem. The elements are present in about 10 000 copies comprising 2.8% of the S.
      digitata genome. As a diagnostic probe IpSdM detects as little as 100 pg DNA of
      both S. digitata and S. labiato-papillosa. It can also detect a single
      microfilaria and a L3 larva making it a valuable tool to monitor cattle and
      mosquito vector populations in the prevention of cerebrospinal nematodiasis.

PMID- 8885467
TI  - Concentrations of steroids and biochemical constituents in follicular fluid of
      buffalo cows during different stages of the oestrous cycle.
AB  - One of the factors controlling ovarian physiology in cattle is the alteration
      that occurs in the hormonal and biochemical composition of follicular fluid.
      Because they are ill-defined in buffaloes, the present study was aimed at
      determining changes in the follicular fluid collected from 197 pairs of buffalo
      ovaries after slaughter. Total oestrogens, progesterone, calcium, inorganic
      phosphorus and total protein were found to be higher before oestrus and reached
      their peak values during oestrus. Glucose concentrations were maximal before
      oestrus. Testosterone, total corticosteroids and acid phosphatase concentrations
      increased during metoestrus peaking during dioestrus. Alkaline phosphatase
      concentration was higher during dioestrus. Ratios and correlations between
      changes in concentrations of the different follicular steroids were determined.

PMID- 8885468
TI  - Evaluation of wound healing of the teat with and without low level laser therapy
      in dairy cattle by laser Doppler flowmetry in comparison with histopathology,
      tensiometry and hydroxyproline analysis.
AB  - Perforated teat wounds in eight lactating Holstein-Friesian cows were closed by
      four suture patterns with or without low level laser therapy (LLLT). Wound
      healing was evaluated by laser Doppler flowmetry (LDF), tensiometry and
      hydroxyproline analysis, and compared with histopathological examination. The
      three-layer pattern provided the best healing of the entire teat. Mucosal
      hyperplasia was observed in Gambee and continuous two-layer pattern while
      eversion of the skin, presence of suture tracts and a greater amount of
      granulation tissue were observed with the continuous and interrupted two-layer
      patterns. The epidermis in LLLT groups more closely resembled the normal
      epidermis, and collagen fibres were denser, thicker and better arranged in LLLT
      than in non-LLLT groups. LDF, tensiometry and hydroxyproline analysis correlated
      well with histopathological examination. The results suggest that LDF, a more
      rapid, less invasive and painless procedure, can replace tensile strength
      measurement or hydroxyproline analysis to assess the progress of teat wound
      healing.

PMID- 8885469
TI  - Hormonal and physiological effects of a 15 hour road journey in sheep: comparison
      with the responses to loading, handling and penning in the absence of transport.
AB  - A controlled study was carried out to investigate the physiological effects of
      road transport on sheep. Animals (n = 10; body weight 38.9 +/- 1.3 kg),
      previously with catheters in their jugular veins, were rounded up and loaded onto
      a vehicle where they were held in a communal pen with eight other lambs. Blood
      samples were taken at 30 min intervals during the next 15 h while the vehicle
      remained stationary or was driven a distance of 548 miles (876 km). Measurements
      were made of plasma concentrations of cortisol, prolactin, creatine phosphokinase
      and lactase dehydrogenase isozymes and also of plasma osmolality, haematocrit and
      body weight; heart rate was also recorded in one animal. Loading and the start of
      driving produced large increases in cortisol and prolactin concentrations. Heart
      rate also increased whereas osmolality and haematocrit decreased. The major
      changes in hormone release occurred in the first 3 h period while, during the
      remaining 12 h, the stimulatory effect of transport was present but small. Body
      weight loss was similar under both stationary and driven conditions.

PMID- 8885470
TI  - New challenges to the faculty in the education of psychiatrists.
AB  - Significant social and economic pressures on academic medicine to become more
      cost conscious and scientifically accountable have led to new tensions in
      psychiatric residency training. Failure to distinguish between changes in
      practice derived from scientific advances and those derived from other sources
      has major implications for the education of future psychiatrists. After providing
      a conceptual framework for understanding current forces that affect residency
      training, the author proposes a new role for the psychiatric faculty, who should
      protect the curriculum and the trainee from shortsighted demands that could lower
      the quality of residency education and make psychiatry a less attractive
      specialty.

PMID- 8885471
TI  - A clinical and interactionist perspective on the bully-victim-bystander
      relationship.
AB  - The authors propose a dialectical conceptual framework for the bully-victim
      bystander interaction often seen in school violence. A clinical and interactional
      typology is proposed for the detection of children falling into these patterns,
      with the goal of affording early and vigorous intervention and consultation
      opportunities with teachers and school administrators.

PMID- 8885472
TI  - Meaning and development in the interpersonal treatment of severe psychopathology.
AB  - As a result of increasing empirical evidence for biological etiologies and
      economic pressures for rapid symptom relief, treatments for patients with severe
      psychopathology have become more directive, behavioral, and biomedical. Since a
      more comprehensive understanding of severe mental disorders is gained through
      both empirical causal explantation and the discovery of meaning (Carpenter,
      1987), clinicians are currently under a greater challenge to help patients
      cultivate more phenomenologically meaningful change experiences. An interpersonal
      treatment approach based upon narrative, intersubjective, developmental, and
      relational principles of understanding severe psychopathology that is
      complementary to behavioral and biomedical intervention is presented. Four
      universal maturational processes (interpersonal self, boundary formation,
      symbolization, response differentiation) are then described and used to
      illustrate how life-story repair, adjustment, and elaboration can create more
      meaningful treatment experiences.

PMID- 8885473
TI  - Symbolic aspects of confabulation following brain injury: influence of premorbid
      personality.
AB  - Confabulation following brain injury is discussed in terms of (1) the conditions
      of brain dysfunction under which it occurs; (2) its association with amnesia, the
      denial syndromes, and reduplicative phenomena; (3) its positive, symbolic,
      adaptive aspects; and (4) the relationship of the content to current stresses and
      premorbid experience.

PMID- 8885474
TI  - Rorschach assessment of cognitive impairment from an object relations
      perspective.
AB  - In 1986, H. Lerner and P. Lerner proposed an object relations model of thinking
      that integrated Piaget's theory of early cognitive development with Mahler's
      theory of separation-individuation. They identified three distinct,
      interdigitated stages, outlined the cognitive task for each stage, detailed the
      necessary role and function of the stage-specific caregiving object, and
      suggested potential cognitive impairments associated with the object not
      fulfilling its function. Herein, this conceptual model is extended to the
      Rorschach. Rorschach indices of cognitive impairments associated with each stage
      were developed. The indices are then applied to the Rorschach records of children
      who were selected as prototypical of specific developmental disorders.

PMID- 8885475
TI  - Teaching psychological testing in a diagnostic seminar: psychodynamics of three
      teacher tasks.
AB  - Despite perceived threats to its viability, psychological testing remains a
      highly valued component in the teaching and training of clinical psychology
      graduate students (Hilsenroth & Handler, 1995; Silverstein, 1995; Watkins,
      Campbell, Nieberding, & Hallmark, 1995). The psychological aspects of educating
      students in assessment, however, represent relatively uncharted terrain. In this
      article, the author focuses on the diagnostic testing seminar in the academic
      setting as a forum for exploring the psychodynamics of three teaching tasks that
      involve: (1) the seminar as classroom and clinic, (2) student self-esteem, and
      (3) perceived threats to the teacher's expertise.

PMID- 8885476
TI  - On fibromyalgia.

PMID- 8885477
TI  - New developments in the myositis syndromes.

PMID- 8885478
TI  - Paul Klee and scleroderma.

PMID- 8885479
TI  - Autoantibodies in systemic sclerosis.

PMID- 8885480
TI  - Creating a research agenda with relevance to cancer nursing practice.
AB  - To be clinically relevant, a research program must seek to answer questions
      considered significant and meaningful by front-line clinicians. This article
      describes the process used by one Nursing Department to identify significant
      clinical questions in cancer nursing that could form the basis for a clinical
      research agenda. Priorities for cancer nursing research were identified in the
      literature and through interviews with all nursing staff. The interview data were
      subjected to a content analysis in which seven overall themes were identified.
      Patient and family themes formed the basis for the research agenda, together with
      the identified priorities from the literature. The primary topic themes for the
      research program include (a) Coping at Home, (b) Information Needs, (c) Symptom
      Distress, (d) Evaluating Care Delivery, and (e) Instrument Development. The
      article will be of interest to nurses wishing to develop a program of clinically
      relevant research.

PMID- 8885481
TI  - Expanding the role of the nurse in clinical trials: the nursing summaries.
AB  - In order to improve the overall quality of clinical trials, the role of the nurse
      should be expanded. The minimum requirement to facilitate nurses' participation
      and the optimal implementation of a clinical research protocol is to provide
      access to the clinical protocol document itself. However, given the high workload
      in an oncology unit, there is often little time for the staff to read the entire
      document. In addition, clinical protocols do not often provide detailed practical
      instructions for delivering treatment, observing patients, managing toxicities,
      and treating complications. A nursing summary of the medical protocol is a
      document that provides a short and easy-to-read selection of protocol-relevant
      information. It enables nurses to safely and more easily implement the research
      protocol and improve the care of patients in clinical trials. Master nursing
      summaries can be prepared centrally by the group responsible for the research
      protocol, while the unit/wards involved in the research can customize or adapt it
      to local needs. The potential benefit of implementing nursing summaries is
      overall improvement of the quality of the study by (a) increasing the reliability
      of nursing care regarding patients' safety, (b) standardizing monitoring and care
      of patients, (c) standardizing preventive measures, (d) proposing similar
      management of complications related to experimental treatments. Moreover,
      discussing nursing summaries may help evaluate workload related to research,
      allowing for better planning and allocation of resources.

PMID- 8885482
TI  - Cancer detection activities coordinated by nursing students in community health.
AB  - This article describes ongoing cancer screening in a low-income and ethnically
      diverse community (primarily Southeast Asian and Hispanic). These services are
      part of the comprehensive care provided in a district nursing community health
      clinical. Screening services occur within the refugee community and include
      mammograms, individualized breast self-exam (BSE) teaching, home follow-up on the
      BSE teaching, and assistance obtaining any additional screening or treatment, if
      necessary. Except for technician activities, students plan, implement, and
      evaluate all services. The first event was in spring 1995, the second in summer
      1995, and the third in fall 1995. Thus far, 85 women have received services.
      Cambodian and Laotian women show the lowest level of knowledge and experience
      related to breast cancer detection. This article provides some of the first data
      on cancer screening for low-income Cambodian and Laotian women in the United
      States. The article also shows how ongoing cancer screening and prevention
      services can be provided to populations that have not been successfully reached
      through usual means, e.g., referral by nurse practitioner, physician, and
      electronic or print media. Specific means of overcoming barriers to screening,
      prevention, and learning are described in detail.

PMID- 8885483
TI  - Risk factors associated with genital HPV infection.
AB  - The genital human papillomavirus (HPV) is directly associated with cervical
      cancer, the second most common form of cancer among women. The study was guided
      by a synergistic interaction model of HPV risk factors. The relative risk of
      selected risk factors and cofactors associated with genital HPV infections was
      identified. Women at highest risk for acquiring an HPV infection had (a)
      initiated sex before age 15, (b) more than four lifetime sex partners, (c) more
      than one "once only" sexual partner, and (d) chosen male sex partners who
      previously had > 16 other female sex partners. Cofactors that increased risk by
      possibly contributing to progression of genital HPV infection were initiating
      oral contraceptive use before age 15 and having acquired more than three other
      sexually transmitted diseases. Past and current smokers were at a slightly higher
      risk compared to nonsmokers. Although other studies have identified risk factors,
      few have identified the relative risk of these factors.

PMID- 8885484
TI  - Evaluation of burnout and job satisfaction in marrow transplant nurses.
AB  - The study examined incidence of burnout syndrome, psychopathology, and job
      satisfaction in bone marrow transplant nurses, in relation to existence of an
      informal psychosocial support programme for staff needs. Forty nurses
      participated in the study completing four standardised measures related to
      burnout, anxiety, depression, satisfaction with aspects of their job, and social
      support. Results indicated that burnout among these nurses was low, and high
      personal accomplishment from working with marrow transplant patients was the
      response of the majority. Job satisfaction was also found to be high, with
      outpatient nurses scoring significantly higher than inpatient nurses in most
      aspects of job satisfaction. One out of four subjects presented with the psychic
      manifestations of the anxiety neurosis, suggesting the stressfullness of the
      marrow transplant environment, which requires a high degree of responsibility and
      advanced nursing skills. Social support was not found to influence burnout,
      psychopathology, or job satisfaction. Presence of depression, low personal
      accomplishment, and dissatisfaction with pay were the variables predicting high
      emotional exhaustion, one of the main components of burnout. These results were
      suggestive of less burned out and more satisfied nurses compared to marrow
      transplant nurses working in environments with no formal or informal staff
      support programmes. This highlights the need for development of support services
      for the nursing staff, allowing them to ventilate their feelings, discuss issues
      of concern to them and seek professional support where necessary.

PMID- 8885485
TI  - Health-related quality of life in women with breast cancer undergoing autologous
      stem-cell transplantation.
AB  - The functional capacity and the health-related quality of life were investigated
      in nine women (ages 23-58 years) undergoing high-dose chemotherapy with
      autologous stem-cell transplantation (ASCT). Data were obtained by using two
      questionnaires: the Sickness Impact Profile (SIP) and the Swedish Health-Related
      Quality of Life Questionnaire (SWED-QUAL). The patients answered the
      questionnaires on three occasions: on admission to the transplant unit, at
      discharge from the unit, and 7-15 weeks after ASCT. It was found that the women
      were affected by the treatment in various dimensions of daily life. The
      transplantation primarily affected their self-rated physical health and
      functions. Their physical-health status was poorest at the time of discharge. The
      women's emotional status was found to be poor during the whole study period. The
      results of the present study indicate that professional nursing is essential for
      breast cancer patients undergoing ASCT.

PMID- 8885486
TI  - Managing spiritual distress in patients with advanced cancer pain.
AB  - Cancer threatens our very existence; when pain is also present, suffering is
      compounded and leads to spiritual distress. This article presents a nursing
      strategy to deal with the responses of clients and families in such complex
      situations. Four case studies were analyzed to describe the methodology and
      applicability of an approach based upon the Dungan model of dynamic integration.
      The goal of the first appointment was to teach clients how to effectively deal
      with the advanced cancer pain that brought them to the center. Presence, caring,
      genuine concern, and active listening facilitated the therapeutic relationship
      and were the hallmarks of nursing modalities. Daily appointments with the nurse
      continued for 6-10 days while clients were also being treated by medical staff.
      Trust was established by reaching the mutual goal of giving the client control
      over pain. Spiritual assessment confirmed the diagnosis. Grief was a
      characteristic of spiritual distress experienced by all clients. Therefore, grief
      counseling was instituted early and reinforced daily. Spiritual counseling,
      cognitive reframing, crisis intervention, and reminiscence were used selectively.
      Because of the complexity of problems faced by families, multi-disciplinary
      referrals were required by all clients. Outcomes were evaluated positively by
      participants. All clients increased hope, participated in the grief process, and
      integrated the possibility of death in such a way as to promote personally
      defined "quality of life" through their waning days.

PMID- 8885487
TI  - Nature of decision-making in the terminally ill patient.
AB  - The increasing emphasis on the consumer's choice in health care treatment has
      contributed to the growing trend for decision-making to be shared between the
      patient and the health care team. If responsibility is to be shared, then it is
      important that health professionals identify the degree to which patients wish to
      participate in the decision-making process, in order that they can assist
      patients to achieve this goal. The seven patient case studies in this pilot study
      explored terminally ill patients' perceptions of their own participation in the
      decision-making process. A simple strategy, through the use of picture cards,
      established patients' actual and preferred forms of decision-making. These cards
      were presented to the patients at various stages of their illnesses, which
      permitted a longitudinal analysis of the decision-making process. Patients
      initially stated that they did not want much input into the decision-making
      process. In this study, however, as patients became more knowledgeable about
      their conditions, they desired greater input into the decision-making process.
      These findings also revealed that, although there was consistency between
      patients' preferred and actual forms of decision-making when they were initially
      admitted to hospital, discrepancies became apparent during the later phases of
      their illness. This emphasises the need for communication between all parties
      involved in health care decisions.

PMID- 8885488
TI  - Programmed instruction: cancer therapy. Associated late effects (III).

PMID- 8885489
TI  - [Traumatic injuries in children].

PMID- 8885490
TI  - Legionnaires' disease in Northamptonshire.

PMID- 8885491
TI  - Child health in the community.

PMID- 8885492
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 8885493
TI  - Effect of primary care referral on emergency department use: evaluation of a
      statewide Medicaid program.
AB  - BACKGROUND AND OBJECTIVES: Medicaid recipients without a regular source of care
      frequently use hospital emergency departments (EDs) for minor problems. This
      study examined whether referring Medicaid patients to primary care physicians and
      obstetricians results in a decrease in ED use and an increase in physician office
      visits. METHODS: The statewide Voluntary Initiative Program (VIP), which referred
      Medicaid patients to primary care physicians and obstetricians without any
      managed care component, was examined. Claims data were reviewed for Medicaid
      clients 0-64 years old who obtained VIP referrals during the first five months of
      the program. The change in rate of visits to hospital EDs and physician offices
      was compared for the study group (n = 444) and for the state's overall Medicaid
      population (n = 40,860). RESULTS: After referral, ED use decreased 24 percent for
      the VIP group and 4 percent for the Medicaid population. During the same period,
      physician office visits increased 50 percent for the VIP group but decreased 13
      percent for the Medicaid population. CONCLUSIONS: Even in the absence of managed
      care, referral to primary care physicians and obstetricians resulted in fewer ED
      visits and more physician office visits. These findings confirm the importance of
      primary care in improving the efficiency of health care delivery for the Medicaid
      population.

PMID- 8885494
TI  - Bugs and bites.

PMID- 8885495
TI  - Complications of total hip arthroplasty.

PMID- 8885497
TI  - Three new antidepressants.

PMID- 8885498
TI  - Pylorid, H. pylori and peptic ulcer.

PMID- 8885499
TI  - Gemcitabine for lung cancer.

PMID- 8885500
TI  - [Quantitative analysis of testicular varicocele by scintigraphy].
AB  - Testicular varcocele is the most common factor affecting male fertility. The
      determental effects of the varicocele on semen quality and fertility are
      codonsidered to be related to its severity. The aim of this study was to
      establish a quantitative radioisotopic method for the diagnosis and evaluation of
      testicular varicocele. 31 men attending our infertility clinic underwent
      scintigraphy with a gamma camera scanner (Apex 415) equipped with a pinhole low
      energy collimator (zoom factor 2). The evaluation was performed in the supine
      position and the collimator at 8.5 cm above the testicular area. The patients'
      red blood cells were labeled in-vivo by injection of SN-pyrophosphate before i.v.
      administration of To-99. An image of the scrotal area was obtained and the
      computer processing consisted of a drawing of the region of interest over the
      area of the varicocele, with background subtraction. The following indices were
      calculated: testes total count, varicocele area (in pixels) and average count per
      pixel (ACPP). The patients also underwent high resolution duplex sonography
      (HRDS) using a Multigon duplex scanner with a 7.5 Mhz transducer. Spermatic vein
      diameter, and reflux when present, were determined. HRDS was performed to compare
      and to validate the results obtained by scintigraphy. In men without varicocele
      mean ACPP was 2.80, in those with mild varicocele 3.76, in those with moderate
      varicocele 5.40 and in those with severe varicocele 7.48. A significant positive
      correlation was found between ACPP values and severity of the varicocele, as
      determined either by the diameter of the spermatic veins or by reflux of blood in
      the veins. We conclude that the ACPP index obtained by this new technique enables
      objective diagnosis and quantitative grading of testicular varicocele.

PMID- 8885501
TI  - [Communication with intubated patients].
AB  - For critically ill patients on assisted respiration caring behavior is
      particularly important. In this paper we review the literature on patient
      satisfaction with medical care and with their communication with the nursing
      staff. Communication skills of staff of intensive respiratory care units were
      studied by direct observation, debriefing of hospitalized patients and by
      interview of discharged patients. Direct observation showed that nurses spent
      only a small proportion of their time talking to patients. The interactions dealt
      with technical rather than emotional matters and consisted mostly of negative and
      discouraging comments rather than positive and supporting messages. Debriefing of
      hospitalized intubated patients revealed a high degree of overall satisfaction
      with care on the one hand, and complaints of communication problems, anxiety and
      anger on the other. Lastly, interviews with discharged patients revealed that as
      many as a quarter of those who could remember their hospitalization reported
      feelings of anxiety, anger, distrust in the staff and difficulty in
      communication. These findings suggest that the nursing staff needs improved
      communication skills. There is evidence that the judicious use of communication
      techniques may improve patient satisfaction, reduce anxiety and reduce duration
      of treatment.

PMID- 8885503
TI  - [Hemorrhagic cystitis as a presenting symptom of acute infection with Salmonella
      typhi].
AB  - Salmonellae are frequently isolated from urine during the course of typhoid
      fever, although cystitis in typhoid is rare. In a young man who had returned from
      India with severe hemorrhagic cystitis, urine and bone marrow cultures confirmed
      the diagnosis of typhoid. Full recovery followed treatment with chloramphenicol.
      This case illustrates an unusual presentation of typhoid fever and the
      illustrates an unusual presentation of typhoid fever and the diagnostic
      difficulties occasionally encountered in patients returning from developing
      countries.

PMID- 8885502
TI  - [Diagnostic and therapeutic approach to sexually transmitted diseases].
AB  - In an ongoing study we evaluated 71 males and 32 females attending our sexually
      transmitted diseases (STD) clinic. Intraurethral or endocervical swab specimens
      were cultured for Neisseria gonorrhea (NG), Ureaplasma urealyticum (UU),
      Mycoplasma homines (MH), Herpes simplex virus (HSV) and Chlamydia trachomatis
      (CT), using an ELISA technique and the polymerase chain reaction (PCR). HIV
      antigen, hepatitis B (HBV) and Treponema pallidum (TP) seropositivity were tested
      by ELISA. Mean age was 33.4 and range 15-72 years. 83 patients (81%) used condoms
      only rarely, 35 (35%) had multiple sexual partners and 83 (81%) were treated
      empirically prior to evaluation. Dysuria and urethral discharge were found in 47
      (45.6%), of whom 34 (33%) were males; the majority of females were asymptomatic.
      A specific etiology for STD was found in 53 patients (51.4%) and 1/3 had more
      than 1 pathogen. CT, UU, MH, HSV, NG and TV were found in 27, 24, 5, 3, 2 and 1,
      respectively. 8 patients were seropositive for HBV and 1 for TP; all were
      seronegative for HIV. CT was the most prevalent pathogen found. All patients with
      STD symptoms should be screened for all sexually transmitted pathogens, since
      many of them have more than 1 pathogen. STD clinics in Israel should be developed
      in conjunction with microbiology laboratories for better management of STD in the
      community.

PMID- 8885504
TI  - [Trimethoprim-sulphamethoxazole-induced meningitis].
AB  - Drug-induced meningitis is rarely included in the differential diagnosis of
      aseptic (usually recurrent) meningitis. A 74-year-old man who suffered from
      recurrent aseptic meningitis following re-exposures to trimethoprim
      sulphamethoxazole (Resprim) is presented. The clinical and laboratory findings
      resembled those found in bacterial meningitis, excluding normal glycorrachia.
      Extensive microbiological, serologic and imaging studies did not disclose any
      relevant findings. All symptoms and signs resolved rapidly following drug
      withdrawal, and findings on follow-up lumbar puncture were normal.

PMID- 8885505
TI  - [Use of aspirin for fever by Russian immigrant children].
AB  - This study describes the therapeutic drug approach in fever in Russian immigrant
      children. 974 recent immigrants with their 208 children were under medical
      treatment at 2 primary care clinics during 1991-1995. They came from 10 republics
      of the Commonwealth of Independence States (CIS, formerly the Soviet Union). In
      the CIS more than 3/4 of children aged 1-18 years had been given aspirin for
      fever. Immigrants brought with them stocks of drugs and their children continued
      to take them as they had in the CIS. This form of treatment is described in the
      official CIS pharmacology book without any mention of potential danger. Use of
      aspirin for fever may be an important factor in the severe hepatic injury and
      encephalopathy seen in Reye's syndrome. Only after intervention of the family
      physician did the immigrants stop this dangerous use of aspirin. During the study
      Reye's syndrome was not seen. Since in Israel purchase of aspirin does not
      require a physician's prescription, family physicians and pediatricians should be
      aware of the potential deleterious effects of aspirin in fever among children.

PMID- 8885506
TI  - [Ticlopidine-induced neutropenia].
AB  - Ticlopidine (TCP) is a drug that inhibits platelet aggregation. Several studies
      have demonstrated its superiority over aspirin in preventing stroke and other
      thromboembolic diseases. However, neutropenia occurs in about 2% of TCP-treated
      patients, which therefore may advance to agranulocytosis, sepsis and death. They
      should be carefully followed with blood counts. We report 2 patients hospitalized
      with severe neutropenia while on TCP, despite having had regular blood counts.
      Their complications underline the need for patient selection and meticulous
      follow-up when ticlopidine is prescribed.

PMID- 8885507
TI  - [Senationalism and responsibility in scientific research].

PMID- 8885508
TI  - [Exertional heatstroke--diagnosis, treatment and prevention].

PMID- 8885509
TI  - [Hepatitis C virus infection and primary mixed cryoglobulinemia].

PMID- 8885510
TI  - [Physical child abuse--characteristics, diagnosis and reporting].

PMID- 8885511
TI  - [Malignant melanoma in childhood and adolescence].

PMID- 8885512
TI  - [Adult attention deficit hyperactivity disorder: "there is such a creature"].

PMID- 8885513
TI  - [Nitric oxide and carbon monoxide--a new generation of neuronal messengers].

PMID- 8885514
TI  - [Back pain in children and adolescents].

PMID- 8885515
TI  - [Knee instability in sportsmen due to anterior cruciate ligament tear].

PMID- 8885516
TI  - [The magic of Archaic Hebrew].

PMID- 8885517
TI  - Optimum care for victims of domestic violence.

PMID- 8885518
TI  - There is no excuse for domestic abuse--reflections on violence.

PMID- 8885519
TI  - Domestic violence...myths and barriers.
AB  - The past 15 to 20 years have seen the birth of a new national awareness of the
      impact of family violence on our national health and resources. The Surgeon
      General of the United States has identified domestic violence as the nation's
      number one health problem. The Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO) has mandated, as of January 1992, that all emergency
      departments and ambulatory care facilities establish guidelines for the
      identification, evaluation, management and referral of adult victims of domestic
      violence. In June 1992, the AMA published guidelines for identification and
      intervention with domestic violence victims. All states now have provisions in
      their laws that define marital rape as a crime, and many states have mandatory
      arrest statutes for men found by the police to be abusing their wives. This
      review identifies some common societal and professional barriers limiting the
      emergency response to domestic violence.

PMID- 8885520
TI  - When children witness domestic violence.
AB  - Children who grow up in violent homes do not necessarily become violent parents
      later on. Some children remain asymptomatic. However, the majority are
      behaviorally disordered and others suffer from PTSD, grief reactions and
      separation anxiety. Children who themselves are not abused are not likely to be
      identified and appropriately treated.

PMID- 8885521
TI  - PTSD among women survivors of domestic violence in Hawaii.
AB  - Empirical evidence suggests that between 33% and 83% of Hawaii women receiving
      services from programs that serve battered women meet diagnostic criteria for
      posttraumatic stress disorder (PTSD). In addition, PTSD symptom severity is
      associated with depression severity, lowered self-esteem, and diminished quality
      of life. Combined with evidence that domestic violence often goes on for years,
      these findings provide additional compelling reasons why domestic violence
      screening should be conducted routinely in medical settings.

PMID- 8885522
TI  - Pandora's box: open it and pass it on! Victim advocates can bring relief to busy
      physicians.

PMID- 8885524
TI  - A police officer's view of domestic violence.

PMID- 8885523
TI  - Identifying family violence: a community prototype incorporating Native Hawaiian
      values and practices.
AB  - The manual, Identifying Family Violence: A Community Prototype Incorporating
      Native Hawaiian Values and Practices is a pioneering effort which health care
      professionals can adapt, expand, or refine in their work with Hawaiians and non
      Hawaiians as well. Our assumption is that a culturally integrated approach is a
      necessary component of a community's strategy to address this escalating problem.
      Family violence is a virus which threatens all of us. It weakens the pohai ke
      aloha (circle of aloha) which binds the family together. When the pohai ke aloha
      is weakened, each family member's mana (vital force) declines. When a familys
      mana is in decline, the lokahi (harmony) within the family and our community is
      disrupted. We, as a community, a society, a nation, cannot afford to stand by and
      condone violence within the family. Ultimately, we all suffer when our families
      are hurting. Hana pono ka puuwai malamalama.. An enlightened heart acts
      accordingly.

PMID- 8885525
TI  - An intervention model for child witnesses of domestic violence.
AB  - The PACT Family Peace Center Children's Program has provided psychoeducational
      group and individual counseling for child witnesses of domestic violence since
      1990.

PMID- 8885526
TI  - Domestic Violence Clearinghouse and Legal Hotline (DVCLH).

PMID- 8885529
TI  - Hypnosis and spasmodic torticollis--report of four cases: a brief communication.
AB  - Dystonia and particularly spasmodic torticollis are neuromuscular disorders that
      are extremely resistant to most therapies (physical, medical, or surgical).
      Torticollis is a unilateral spasm of the neck muscles, particularly of the
      sternocleidomastoid, that produces violent, tonic turning of the head to one
      side. The etiology remains uncertain, although the role of psychogenic factors
      has been emphasized. This article reviews the literature and reports four cases
      of spasmodic torticollis treated successfully with hypnosis. In all four cases,
      psychogenic causes were involved. Postural hypnosis (i.e., hypnosis in the
      standing position) was employed to counteract and minimize muscle spasms due to
      postural reflexes. A hypnobehavioral approach was adopted along with hypnotic
      strategies that included hierarchical desensitization, sensory-imaging
      conditioning, ego-boosting suggestions, and hypnosis-facilitated differential
      muscle retraining. In two cases, a combined hypnosis and electromyographic
      biofeedback approach was used to equilibrate and retrain affected neck muscles.
      Although the hypnotherapeutic process took several months to induce and stabilize
      significant changes, outcome results were good to excellent in all cases, with
      marked reduction of the torticollis and the hypertrophy of the neck muscles as
      well as a reduced interference of symptoms in daily living.

PMID- 8885530
TI  - Catalepsy tests: what do they tell us?
AB  - In a survey of 200 clinicians regarding their use of catalepsy tests, three
      fourths of the respondents indicated that they used these tests. In light of this
      response, and considering both the scientific importance of being able to
      identify the presence of hypnosis and the fact that catalepsy may account for up
      to eight of the other indications of hypnosis in use, it is relevant to inquire
      into the reliability and validity of catalepsy tests. It was found that of the
      three tests of catalepsy currently in use, only one has the potential for being a
      test of hypnosis proper and can also justifiably be said to be "of catalepsy."
      This one test, however, has many serious weaknesses that need to be eliminated if
      it is to be truly useful.

PMID- 8885531
TI  - Hypnotic susceptibility, imaging ability, and anagram-solving activity.
AB  - Anagram-solving activity was examined as a function of hypnotic susceptibility
      level and imaging ability. In Experiment 1, anagrams that were composed of sets
      of letters that formed actual words (word anagrams), but when unscrambled formed
      other words, were compared to sets of letters that formed nonwords (nonsense
      anagrams). Word anagrams required more time to solve than nonsense anagrams.
      Also, fewer word anagrams were correctly solved compared to nonsense anagrams.
      Those individuals judged both high in hypnotic susceptibility and vivid in
      imaging ability demonstrated the best performance. In Experiment 2, anagrams that
      when unscrambled formed high-imagery words were compared to those that formed low
      imagery words. High-imagery-word anagrams were solved more quickly and correctly
      than low-imagery-word anagrams. Such activity was best demonstrated by
      individuals who were judged to be both high in hypnotic susceptibility and vivid
      in imaging ability. These results are discussed in terms of strategies for
      solving anagrams and the individual differences that appear to be associated with
      using such strategies.

PMID- 8885532
TI  - The Hypnotic Simulation Index: successful discrimination of real versus
      simulating participants.
AB  - Researchers have attempted to find a method that accurately and reliably
      discriminates hypnotized individuals from those who are simulating hypnosis.
      Although an extensive literature exists in this area, researchers have failed to
      identify a discriminator that is consistently successful with a majority of the
      individuals who are tested. In the current study, 43 hypnotized and 37 simulating
      participants were categorized on the basis of their scores on the newly created
      Hypnotic Simulation Index (HSI). Using all 31 items of the HSI as predictors, 94%
      of the participants were correctly classified. In addition, a reduced set of only
      15 items correctly classified 96% of the participants. These results suggest that
      the HSI is effective in discriminating hypnotized and simulating participants.

PMID- 8885533
TI  - Memory liabilities associated with hypnosis: does low hypnotizability confer
      immunity?
AB  - Retrospective analyses of data from the authors' program of research on hypnosis
      and memory are presented, with special emphasis on effects observed among low
      hypnotizable individuals. In Experiment 1, participants completed seven forced
      recall trials in an attempt to remember a series of pictures that had been shown
      1 week earlier. For half the participants, the middle five trials were carried
      out using hypnotic procedures; the remaining participants performed all recall
      attempts in a motivated waking condition. Hypnosis failed to enhance correct
      recall for either high or low hypnotizable participants beyond the hypermnesia
      and reminiscence effects associated with repeated retrieval attempts over time.
      However, whereas high hypnotizable participants produced substantial numbers of
      confident recall errors (i.e., intrusions) independent of the use of hypnosis,
      low hypnotizable participants exposed to hypnotic procedures reported
      significantly more intrusions than their counterparts in the waking condition. In
      Experiment 2, participants were asked to identify whether specific recollections,
      reported during two forced-interrogatory recall tests conducted 1 week earlier,
      had originated in the first or second of those tests. A general bias to
      misattribute previously reported recollections to the first of two recall
      occasions was observed; however, the effect was greatest among low hypnotizables
      who had undergone the second recall attempt in hypnosis. The findings imply that
      highly hypnotizable individuals are not unique in their vulnerability to
      distortions of memory induced by hypnotic techniques. Individuals of lesser
      hypnotic capacity also manifest memory alterations when exposed to such
      procedures.

PMID- 8885534
TI  - A spot of tea.

PMID- 8885535
TI  - Fractures and nonunions of the scaphoid.
AB  - Fractures of the scaphoid are the most common of all fractures of the carpal
      bones. Scaphoid collapse and angular deformity may develop after fractures.
      Scaphoid nonunion often complicates scaphoid fractures especially if the
      diagnosis is missed initially, and adequate timely treatment is not provided.
      Displaced unstable fractures also have a tendency to develop nonunion. The
      tenuous vascular anatomy of the scaphoid, the inherent biomechanical instability
      of scaphoid fractures, and the difficulty of radiographic diagnosis are the
      culprits of nonunion. Established scaphoid nonunion is a challenging and
      difficult problem to treat and more so is the treatment of failed nonunion after
      grafting. New methods of diagnosis and treatment of scaphoid injuries are
      constantly evolving. One common method of treating scaphoid nonunion with angular
      deformity is length restoration using a wedge bone graft and Herbert screw
      fixation through a palmar approach. Early diagnosis and attention to details of
      surgical technique are necessary for successful treatment outcome. The purpose of
      this report is to review the basic science, diagnosis, and treatment of scaphoid
      fractures and nonunions.

PMID- 8885538
TI  - Initiation of prenatal care among women having a live birth in Oklahoma. The
      Maternal and Child Health Service, Oklahoma State Department of Health.

PMID- 8885537
TI  - Ipecac, Indian turnip, and sassafras: a sampling of American Indian medicine.

PMID- 8885536
TI  - The scimitar syndrome: demonstration with magnetic resonance imaging.
AB  - The authors describe a case of scimitar syndrome, which is a rare congenital lung
      abnormality characterized by partially anomalous pulmonary venous return. MRI
      findings as well as other methods of diagnosis are discussed.

PMID- 8885539
TI  - Major anomalies in consecutive births in south of Beirut. A preliminary report
      about incidence and pattern.
AB  - A prospective study of major congenital anomalies (MCA) in the newborn is planned
      for 3 years. This preliminary report included 2161 consecutive newborns who were
      examined in one year for the presence of MCA in one center whose population is
      mostly of unfavourable living conditions. Major anomalies were found in 32
      infants at incidence of 14.8/1000 (B). 29 infants with full description included
      21 with a single and 8 with multiple MCA, 5 of whom were non syndromal and 3 of
      sequence type Skeletal anomalies were leading among the group followed by neural
      tube fusion defects (NTFD) forming 21.05% and 18.42% of total anomalies
      respectively. Incidence of NTFD (3.23%) and of esophageal atresia (1.38%) was
      higher than in many other western and middle eastern reports. No cases of
      mongolism were observed among the group putting its incidence below the usually
      reported figures. Incidence of low birth weight (LBW) was 5.7% among the studied
      population and 25% among the group of patients. Incidence of MCA among the group
      of LBW was 6.5%. Perinatal death was 2.82% among the whole group of newborns, 50%
      among malformed infants who formed 26.22% of perinatal death. 62.5% of cases were
      amerable to surgery.

PMID- 8885540
TI  - The diabetic foot: a diagnostic and therapeutic challenge (Part I).

PMID- 8885541
TI  - Direct drug control of the vascular wall.

PMID- 8885542
TI  - Advances in myocardial protection?

PMID- 8885543
TI  - Vasoreactivity of the radial artery: comparison with the internal mammary and the
      gastroepiploic arteries. Implications for coronary artery surgery.

PMID- 8885544
TI  - Combined coronary and femoral revascularization using an ascending aorta to
      bifemoral bypass.

PMID- 8885545
TI  - [Atrial defibrillation].

PMID- 8885546
TI  - Amiodarone-induced dysthyroidism. Pitfalls and management.

PMID- 8885547
TI  - Renovascular hypertension: who is at risk and how to treat.

PMID- 8885548
TI  - Aberrant right subclavian artery aneurysm--a surgical review.
AB  - Aneurysms of an aberrant subclavian artery are rare. They are usually secondary
      to atherosclerosis. Dysphagia is the most common presenting symptom. The
      diagnosis of the lesions is easily established by CT scan or MRI. Biplane
      arteriography is necessary in order to clearly analyse the aortic arch and its
      branches. Surgical resection is usually indicated. We treated a patient who
      suffered from an aneurysm of an aberrant subclavian artery. The surgical
      technique is detailed as well as a review of all the surgical cases of the
      literature.

PMID- 8885549
TI  - Cardiovascular protection and repair and angiotensin converting enzyme (ACE)
      inhibitors.

PMID- 8885550
TI  - The value of chest X ray in asymptomatic young adults with positive PPD test.
AB  - The value of chest radiograph in the management of asymptomatic tuberculin
      positive (> 10mm) individuals is controversial. We reviewed the results from two
      centers in Beirut: The Employment Health Program at Makassed General Hospital
      (MGH) in 1984 and the Visa Applicants Program at the American University of
      Beirut Medical Center (AUB-MC) 1990-1991. All subjects were free of symptoms and
      their physical examination was unrevealing. At MGH, out of 450 PPD tests, 46
      (10.2%) were positive and chest-x-rayed. Forty-four (95.6%) were reported as
      normal, one had a chronic inflammation and one had metastasis. At AUB-MC, 67 PPD
      positive persons were x-rayed, of whom 65 (97%) were normal and the remainder two
      showed inactive granulomatous disease. No active tuberculosis case was detected.
      Isoniazid (INH) prophylaxis is recommended in the above selected group of
      subjects. We conclude that routine chest radiograph is of no significant value in
      the management of asymptomatic positive skin reactors, age group (16-35). A
      larger study is being undertaken for further delineating the usefulness, as well
      as the cost effectiveness of routine chest X ray being done on the above
      mentioned groups of individuals in our population.

PMID- 8885551
TI  - Acute fatty liver of pregnancy.

PMID- 8885552
TI  - Falls in the elderly.

PMID- 8885553
TI  - Diagnosis and treatment of pancreatic and ampullary cancer.

PMID- 8885554
TI  - Angiotensin converting enzyme inhibitors: basics (Part I).

PMID- 8885555
TI  - Actual questions and strategies of environmental protection and environmental
      medicine--aspects for Lebanon?

PMID- 8885556
TI  - Vitaminology.

PMID- 8885557
TI  - Carotid artery disease practice guidelines for the general practitioner.
AB  - Carotid artery disease is a major public health concern. Cost-effective screening
      can be effected in a certain cohort of patients, especially if the referring
      physician uses vascular laboratories with expert technologists. Once the grade of
      stenosis, plaque morphology, and the patient's life expectancy and co-morbid
      conditions are known, the physician can offer the patient the safest therapeutic
      option. If the patient is a surgical candidate, it is important for the general
      practitioner to remember that the efficacy of carotid surgery is a balance
      between the risk of the surgeon versus the risk of the plaque Patient selection
      for low risk and surgeon selection for good track record should be secured before
      subjecting the patient to surgical intervention.

PMID- 8885558
TI  - Methicillin resistant Staphylococcus aureus (MRSA): disease spectrum, biological
      characteristics, resistant mechanisms, and typing methods.

PMID- 8885559
TI  - Lactose intolerance. Diagnosis and dietary treatment with milk substitutes.

PMID- 8885560
TI  - Mondor's disease. A forgotten cause of anterior chest pain.
AB  - A 50-year-old woman sought a rheumatological consultation for anterior chest pain
      of three weeks duration. The diagnosis of superficial phlebitis of the anterior
      chest wall (Mondor's disease) was made. This was confirmed thereafter by the
      pathological report. She was treated with a non-steroidal anti-inflammatory drug
      Oxyphenylbutazone (Tanderil) and made a prompt recovery.

PMID- 8885561
TI  - When children have to die.

PMID- 8885562
TI  - Challenges in identifying children for palliative care.

PMID- 8885563
TI  - Pediatric palliative care: building the model, bridging the gaps.
AB  - Currently the provision of palliative care is patchy and inconsistent. What is
      needed is a systematic and comprehensive approach to all children with
      significant life-threatening diseases to ensure that their special needs are met.
      If timely palliative care is to be available to the terminally ill child, a shift
      in perspective is required as to how and when such support is introduced.
      Developing resources with the people who provide frontline care for these
      children and their families enables health professionals to assume this special
      aspect of care with more confidence and competence. Consultation with a
      palliative care service is still required for some difficult problems, but the
      focus of care should be based primarily where the child and family are cared for.
      By linking the primary care team with the palliative care program early on in the
      disease course, resources can be combined and bolstered to provide the best
      available support to the dying child and to those whose lives are committed to
      caring for that child.

PMID- 8885564
TI  - An international perspective on palliative care for children.

PMID- 8885565
TI  - Home care of the dying child.

PMID- 8885566
TI  - Beyond pain: the existential suffering of children.

PMID- 8885567
TI  - Pediatric palliative medicine: obstacles to overcome.
AB  - The care of the dying child involves an appreciation of issues that are distinct
      from those faced in adult palliative care. Obstacles to effective palliative care
      for children start with the very basic need to assure pain control, and include
      difficult ethical issues of limits to treatment and the determination of the
      child's best interests. The remarkable progress in medicine has resulted in the
      ability of medical science to more accurately diagnose and treat most symptoms of
      the terminally ill. What remains underrepresented is the teaching and application
      of the tools at hand that can provide comfort and relief to the dying. In
      children, an appreciation of the whole person, including the unique role of
      parents, is needed when we are confronted with the difficult choices faced at the
      end of life. Given the lack of objective data on such basic issues as the
      assessment of pain, the relationship of thirst to dehydration, and the ability of
      technology to prolong the quality of life, it remains imperative that we remain
      open to different interpretations of the appropriate use of medical therapies. In
      areas such as the pharmacodynamics of opiates, where good data already exist, it
      remains unacceptable to have children suffer because of misperceptions and
      incorrect assumptions about appropriate drug use. The task of understanding the
      complexity of the child and family as they live through the experience of the
      child's dying is enormous. The need to give care and attempt the relief of
      suffering is just as great as the need to cure and should be no less an ultimate
      goal of medicine.

PMID- 8885568
TI  - Intractable pain in children with terminal cancer.

PMID- 8885569
TI  - Ethical aspects of pediatric palliative care.

PMID- 8885570
TI  - Refractory symptoms and terminal sedation of children: ethical issues and
      practical management.

PMID- 8885571
TI  - Attitudes and beliefs about medication and pain management in children.

PMID- 8885572
TI  - Family responses when a child with cancer is in palliative care.

PMID- 8885573
TI  - The broken heart: anticipatory grief in the child facing death.

PMID- 8885574
TI  - Mania in children.

PMID- 8885576
TI  - Persistent depression.

PMID- 8885575
TI  - Toward a rational prescribing practice.

PMID- 8885577
TI  - Persistent depression.

PMID- 8885578
TI  - Psychotropic toxicity.

PMID- 8885579
TI  - Hyperactivity and ADHD.

PMID- 8885580
TI  - Obsessive-compulsive disorder in children and adolescents: a review of the past
      10 years.
AB  - OBJECTIVE: To review the literature on pediatric obsessive-compulsive disorder
      (OCD) from the perspective of information relevant to American Board of
      Psychiatry and Neurology recertification in child and adolescent psychiatry.
      METHOD: The clinical and research literatures were systematically searched or
      articles that address the diagnosis and treatment of pediatric OCD. RESULTS:
      Drawing from the literature and their own clinical experience, the authors note
      that (1) OCD is a common neuropsychiatric disorder; (2) comorbidity is common,
      especially with tic, attention-deficit, anxiety, and affective disorders; (3) OCD
      following group A beta-hemolytic streptococcal infection may define an autoimmune
      sub-grouping calling for immunomodulatory treatments; and (4) OCD-specific
      cognitive-behavioral psychotherapy and pharmacotherapy with a serotonin reuptake
      inhibitor define the psychotherapeutic and pharmacotherapeutic treatments of
      choice, respectively. CONCLUSION: Child psychiatrists should be familiar with the
      differential diagnosis and treatment of OCD.

PMID- 8885581
TI  - Regulatory issues in pediatric psychopharmacology.
AB  - Labeling claims for the effectiveness of drugs in the treatment of psychiatric
      illnesses in children and adolescents must be based on data from adequate and
      well-controlled investigations. The preferred design for demonstrating the
      effectiveness of a drug in pediatric psychopharmacology is generally a placebo
      controlled trial. Safety information in labeling may be derived from more diverse
      sources. The Food and Drug Administration (FDA) has taken several steps to
      encourage more informative labeling of drugs for pediatric use, including a
      recent labeling initiative that emphasizes the possibility of extrapolating
      effectiveness data from adult studies to pediatric populations under appropriate
      circumstances. This recently finalized regulation requires pharmaceutical
      sponsors to reexamine existing data for their drugs to determine whether there is
      a sufficient basis for modifying labeling for pediatric use. Included in this new
      rule is a reminder that in certain situations the FDA may require new pediatric
      studies, thereby signaling the FDA's determination to improve labeling for the
      pediatric use of drugs. Improved preclinical models for predicting drug effects
      on growth and development, as well as improved clinical methods for detecting
      such changes, need to keep pace with the expansion of research in pediatric
      psychopharmacology.

PMID- 8885582
TI  - Conducting research with children: legal and ethical issues.
AB  - Research with children and mentally disabled individuals raises difficult legal
      and ethical issues. It is the obligation of researchers and those who review
      research to protect both the rights and welfare of research subjects. Ethicists,
      legal scholars, and national commissions have examined the circumstances under
      which it is acceptable to use incompetent people as research subjects, since they
      are unable to provide consent for participation. Furthermore, there is an
      extensive set of federal rules that govern the use of children as research
      subjects. Children may be used as research subjects after a careful weighing of
      risks and benefits, and as long as they participate in the decision to the extent
      they are able to do so. However, research projects that will not provide children
      with direct benefit, such as some placebo-controlled trials, raise particularly
      difficult issues concerning the protection of these subjects. While biomedical
      research is an important and socially desirable undertaking, it must proceed only
      when the rights and welfare of the subjects are scrupulously protected.

PMID- 8885583
TI  - Traditional and alternative research designs and methods in clinical pediatric
      psychopharmacology.
AB  - OBJECTIVE: To review both traditional and alternative research designs and
      methods in pediatric psychopharmacology. METHOD: Study designs used in clinical
      trials in psychiatry were selected for review with the special considerations of
      pediatric psychopharmacological trials in mind. Where possible, a reference to a
      specific published trial in pediatric psychopharmacology was provided for each
      design. RESULTS: It appears that pediatric psychopharmacology trials require a
      relatively greater flexibility in design to avoid significant study biases.
      Alternative research designs may be preferable to the traditional approaches,
      particularly when the use of the latter may raise important issues of
      feasibility. CONCLUSIONS: Evolution of a clinical research hypothesis to a study
      protocol in pediatric psychopharmacology is a manageable task if one keeps in
      mind essential elements such as selection of study design, population, sample
      size, treatment duration, and efficacy assessments.

PMID- 8885585
TI  - Bupropion hydrochloride in attention deficit disorder with hyperactivity.
AB  - OBJECTIVE: This is a multisite, double-blind, placebo-controlled trial to
      determine the safety and efficacy of bupropion in the treatment of children with
      attention deficit disorder with hyperactivity (ADDH). METHOD: In a four-center,
      double-blind comparison of bupropion (n = 72) and placebo (n = 37), children aged
      6 to 12 years meeting DSM-III criteria for ADDH were randomized to receive
      bupropion 3 to 6 mg/kg per day or placebo, administered twice daily, at 7 A.M.
      and 7 P.M. Measures of efficacy included the Conners Parent and Teacher
      Questionnaires (93-item, 39-item, and 10 item), Clinical Global Impressions
      Scales of Severity and Improvement, the Sternberg Short-Term Memory Task, and the
      Continuous Performance Test. Screen and posttreatment physical examinations,
      electrocardiograms, electroencephalograms, and clinical laboratory evaluations
      were performed. Height, weight, and vital signs were measured and adverse
      experiences were assessed weekly. RESULTS: A significant treatment effect,
      apparent as early as day 3, was present for both conduct problems and
      hyperactivity on the Conners 10-item and 39-item teacher's checklist, and at day
      28 for conduct problems and restless-impulsive behavior on the 93-item parent
      questionnaire. Findings were of smaller magnitude for parent ratings than teacher
      ratings. Significant treatment effects were present on both the Continuous
      Performance Test and memory retrieval test. Effect sizes of bupropion/placebo
      differences for teacher and parent ratings in this study were somewhat smaller
      than for standard stimulant drugs used to treat ADDH. Bupropion appeared to be
      well tolerated in most children. Dermatological reactions were twice as frequent
      in the drug group as the placebo group, with four reactions involving rash and
      urticaria that were serious enough to require discontinuation of medication.
      CONCLUSIONS: Bupropion may be a useful addition to available treatments for ADDH.
      Comparative trials with such standard drugs as methylphenidate are warranted to
      determine the relative clinical merits of bupropion.

PMID- 8885584
TI  - Medication treatment strategies in the MTA Study: relevance to clinicians and
      researchers.
AB  - OBJECTIVE: Clinicians have difficulty applying drug research findings to clinical
      practice, because research protocols use methods different from those used in
      daily office practice settings. METHOD: To design a medication protocol for a
      multisite clinical trial involving 576 children with attention-deficit
      hyperactivity disorder (ADHD) while maintaining relevance to clinical practice,
      investigators from the NIMH Collaborative Multisite Multimodal Treatment Study of
      Children with Attention-Deficit/Hyperactivity Disorder (MTA study) developed
      novel medication strategies. These were designed to work either in a monomodal or
      multimodal format and to ensure standard approaches are used across diverse
      sites. Each child randomized to medication (projected N = 288) is individually
      titrated to his or her "best" methylphenidate dose and has individual ADHD
      symptoms monitored. Decision rules were developed to guide "best dose" selection,
      dose changes, medication changes, the management of side effects, and integration
      with psychosocial treatments. CONCLUSIONS: The MTA study uses a controlled method
      to standardize the identification of each child's "best" methylphenidate dose in
      a national, multisite cooperative treatment program. Although the titration
      protocol is complex, the study's individual dosing approach and algorithms for
      openly managing ADHD children's medication over time will be of interest to
      clinicians in office practice.

PMID- 8885586
TI  - Male testosterone linked to high social dominance but low physical aggression in
      early adolescence.
AB  - BACKGROUND: The association of male pubertal testosterone with social dominance
      and physical aggression was studied in a population sample of boys followed from
      age 6 to 13 years to understand the origin of the links between violent behavior
      and gonadal hormones. METHOD: Physical aggression was assessed from the end of
      kindergarten to the end of elementary school by teachers and peers (aged 6 to 12
      years). Social dominance and testosterone levels were assessed at 13 years of age
      during a 1-day visit to a laboratory with four unfamiliar peers. RESULTS: Boys
      perceived as socially dominant by unfamiliar peers were found to have
      concurrently higher levels of testosterone than boys perceived as less socially
      dominant. In contrast, boys who had a history of high physical aggression, from
      age 6 to 12, were found to have lower testosterone levels at age 13 compared with
      boys with no history of high physical aggression. The former were also failing in
      school and were unpopular with their peers. CONCLUSIONS: Both concurrent and
      longitudinal analyses indicated that testosterone levels were positively
      associated with social success rather than with physical aggression. High
      testosterone levels in adolescent boys may thus be regarded as a marker of social
      success in a given context, rather than of social maladjustment as suggested in
      previous studies.

PMID- 8885587
TI  - Can emotions and themes in children's play predict behavior problems?
AB  - OBJECTIVE: To empirically test whether systematic examination of emotions and
      themes in children's play can provide useful information about childhood
      problems. METHOD: Using the MacArthur Story-Stem Battery and coding system,
      distress and destructive themes (aggression, personal injury, and atypical
      negative responses) were coded from the play of 51 children at ages 3, 4, and 5
      years, in a low-risk, nonclinical volunteer sample. To measure behavior problems,
      both parents completed the Child Behavior Checklist at all ages, and teachers
      completed the Teacher's Report Form when the children reached 5 years of age.
      RESULTS: Both distress and destructive themes in the play of 4- and 5-year-olds
      were found to correlate with externalizing behavior problems as rated by parents
      and teachers. CONCLUSIONS: Children who display more distress during play at 4
      and 5 years of age and who demonstrate destructive themes at 4 and 5 years of age
      appear to have more externalizing behavior problems, as rated by their parents
      and teachers. These results provide empirical support for the use of play as an
      assessment tool in young children. The findings suggest approaches to and
      limitations of play interpretation.

PMID- 8885588
TI  - Borderline personality disorder in adolescents: affective and cognitive features.
AB  - OBJECTIVE: To examine systematically the affective and cognitive features of
      borderline personality disorder (BPD) in adolescence, using standardized measures
      of these constructs and controlling for depression. METHOD: Nineteen depressed
      female adolescents with BPD were compared with 21 non-BPD depressed inpatients on
      measures of affect and cognitive style. RESULTS: Both BPD and non-BPD adolescents
      endorsed significantly elevated levels of self-reported depression, anger,
      anxiety, hopelessness, self-deprecatory attributional style, and external locus
      of control. Adolescents with BPD endorsed significantly poorer self-concept than
      their non-BPD peers; this difference was not an artifact of depressive severity.
      CONCLUSIONS: The findings indicate that adolescents with BPD experience
      significant impairments in self-concept, suggestive of pervasive emptiness and
      identity disturbance associated with BPD.

PMID- 8885589
TI  - Defense mechanisms in adolescents as a function of age, sex, and mental health
      status.
AB  - OBJECTIVE: To modify an existing instrument to provide a valid assessment of
      defense mechanisms in adolescents and to examine defense structure and usage as a
      function of age, sex, and mental health status. METHOD: Six hundred ninety-three
      subjects (187 nonclinic adolescents, 229 internalizing females, 99 incarcerated
      male delinquents, and 178 nonclinic adults) completed the modified Defense Style
      Questionnaire (DSQ), which yielded 19 defense scores. RESULTS: Factor analyses of
      the 19 defense scores on the adolescent sample yielded three factors: Immature,
      Mature, and Prosocial Defenses. These were similar to those from studies of
      adults. Additional factor analyses were conducted on defense scores of subjects
      grouped by age, sex, and mental health status. The Immature and Mature Factors
      were relatively consistent across groups, but the Prosocial Factor varied by
      group. Multivariate analyses of variance and analyses of variance on individual
      and composite defense scores revealed differences by age, sex, and mental health
      status. CONCLUSIONS: Although the modified DSQ needs further work to improve its
      psychometric properties, it is clearly fruitful to assess adolescent defense
      mechanisms. Results from extant studies of adults and males on the structure of
      defenses cannot be validly extrapolated to other age groups and to females.

PMID- 8885590
TI  - Childhood sexual abuse and psychiatric disorder in young adulthood: I. Prevalence
      of sexual abuse and factors associated with sexual abuse.
AB  - OBJECTIVE: To present accounts of the prevalence of childhood sexual abuse (CSA)
      and social, family, and related factors that are associated with increased risk
      of CSA, using data gathered during an 18-year longitudinal study of a New Zealand
      birth cohort. METHOD: A birth cohort of more than 1,000 children born in
      Christchurch (New Zealand) was studied prospectively to the age of 16 years. At
      age 18, retrospective reports of CSA were obtained. RESULTS: Of the cohort, 10.4%
      (17.3% of females and 3.4% of males) reported having experienced CSA before the
      age of 16 years. Rates of severe abusive experiences involving intercourse were
      lower: 5.6% of females and 1.4% of males reported abuse involving attempted or
      completed intercouse. Multivariate analyses that the risk of CSA was elevated
      among females (p < .0001), those exposed to high levels of marital conflict (p <
      .005), those reporting low parental attachment (p < .001), those reporting high
      levels of paternal overprotection (p < .005), and those with parents who reported
      alcoholism/alcohol problems (p < .05). The level of prediction of CSA from
      childhood and family factors was not sufficient to identify individuals at risk
      of CSA with any degree of accuracy. CONCLUSIONS: CSA was not an uncommon
      experience in this cohort. Those most likely to be exposed to CSA were girls
      reared in families in families characterized by high levels of marital conflict
      and impaired parenting and in families having parents with adjustment problems.

PMID- 8885591
TI  - Childhood sexual abuse and psychiatric disorder in young adulthood: II.
      Psychiatric outcomes of childhood sexual abuse.
AB  - OBJECTIVE: This is the second in a series of articles that describe the
      prevalence, correlates, and consequences of childhood sexual abuse (CSA) in a
      birth cohort of more than 1,000 New Zealand children studied to the age of 18
      years. This article examines the associations between reports of CSA at age 18
      and DSM-IV diagnostic classifications at age 18. METHOD: A birth cohort of New
      Zealand children was studied at annual intervals from birth to age 16 years. At
      age 18 years retrospective reports of CSA prior to age 16 and concurrently
      measured psychiatric symptoms were obtained. RESULTS: Those reporting CSA had
      higher rates of major depression, anxiety disorder, conduct disorder, substance
      use disorder, and suicidal behaviors than those not reporting CSA (p < .002).
      There were consistent relationships between the extent of CSA and risk of
      disorder, with those reporting CSA involving intercourse having the highest risk
      of disorder. These results persisted when findings were adjusted for
      prospectively measured childhood family and related factors. Similar but less
      marked relationships between CSA and nonconcurrently measured disorders were
      found. CONCLUSIONS: The findings suggest that CSA, and particularly severe CSA,
      was associated with increased risk of psychiatric disorder in young adults even
      when due allowance was made for prospectively measured confounding factors.

PMID- 8885592
TI  - Age of onset of sexual abuse: relationship to sexually inappropriate behaviors.
AB  - OBJECTIVE: To examine how the age of onset of sexual abuse predicted
      inappropriate sexual behaviors in a sample of seriously mentally ill youths.
      METHOD: A retrospective chart review was completed for all youths treated from
      1987 through 1992 at a tertiary care public sector psychiatric hospital (n =
      499). Subjects were grouped according to the age at which they were first
      sexually abused: no sexual abuse (n = 225), 0 through 3 years (n = 78), 4 through
      6 years (n = 105), 7 through 12 years (n = 71), and 13 through 17 years (n = 19).
      RESULTS: The rates of sexually inappropriate behaviors in subjects with sexual
      abuse histories were quite substantial, ranging from 79.5% of the 0- through 3
      year group to 42.1% of the 13- through 17-year group. Subjects first abused
      during early childhood, especially during the ages 0 through 3 years, had
      significantly elevated rates of hypersexual, exposing, and victimizing sexual
      behaviors. They also were significantly younger at the time of admission, came
      from more disrupted family settings, and had significantly higher rates of
      physical abuse, neglect, chronic sexual abuse, sexual abuse by either
      parent/stepparent and a higher total number of victimizers. When logistic
      regression analyses were done to examine the predictive power of potential risk
      factors, early age of onset of sexual abuse was the most significant predictor of
      all three types of inappropriate sexual behaviors. CONCLUSIONS: Onset of sexual
      abuse prior to 7 years of age was significantly associated with hypersexual,
      exposing, and victimizing sexual behaviors. Early sexual abuse is also associated
      with a number of other poor prognostic factors, and further research is needed to
      define how these variables interact.

PMID- 8885593
TI  - Relationship between early abuse, posttraumatic stress disorder, and activity
      levels in prepubertal children.
AB  - OBJECTIVE: To examine the relationship between early physical and sexual abuse,
      posttraumatic stress disorder (PTSD), major depression, and activity levels in
      prepubertal children. METHOD: Nineteen unmedicated children with documented abuse
      (9.4 +/- 2.3 years; 6 girls, 13 boys) were compared with 15 healthy controls (8.3
      +/- 1.9 years; 6 girls, 9 boys). Diagnoses were derived from structured
      interviews (Schedule for Affective Disorders and Schizophrenia for School-Age
      Children-Epidemiologic Version). Motionlogger actigraphs collected activity data
      for 72 continuous hours in 1-minute epochs. RESULTS: Overall, abused children
      were 10% more active than normal children (p < .05) and displayed a paucity of
      periods of low-level daytime activity (p < .01). Abused children with PTSD were
      largely responsible for the increase in activity. Abused children with PTSD had a
      robust and normal circadian activity rhythm. Abused children in whom PTSD failed
      to develop had an attenuated circadian amplitude compared with subjects with PTSD
      (101% versus 93%, p < .01) and were phase-delayed by 61 minutes versus controls
      (p = .01). Early onset of abuse was significantly associated with greater
      likelihood of the development of PTSD and hyperactivity. Later age of abuse was
      associated with circadian dysregulation. CONCLUSIONS: These preliminary
      observations indicate that abused children with PTSD have activity profiles
      similar to those of children with attention-deficit hyperactivity disorder, while
      abused children without PTSD have activity profiles more similar to those of
      depressed children.

PMID- 8885594
TI  - Childhood family problems and current psychiatric problems among young violent
      and property offenders.
AB  - OBJECTIVE: The main objective was to examine whether young property and violent
      offenders would differ from each other in the prevalence of childhood abuse and
      neglect experiences, prevalence of various early family problems, and prevalence
      of disruptive behavior disorders, depression, and substance use. METHOD:
      Childhood abuse and neglect assessments and family problems were based on
      interview, questionnaire, and file data. Psychiatric diagnoses were made on the
      basis of a structured clinical interview. RESULTS: There were no statistically
      significant differences in the prevalence of childhood physical or psychological
      abuse, or neglect between the groups. According to the files, physical abuse was
      experienced by 57.5% of the violent offenders compared with 37% of the property
      offenders (p = .10). The prevalence rates of family problems were not different
      in the groups. Seventy-one percent of the violent group abused street drugs
      compared with 51% of the property group (p < .05), but the groups did not differ
      in disruptive behavior disorders, alcohol abuse/dependence, or depression.
      CONCLUSIONS: The property and violent offenders were surprisingly similar to each
      other in childhood experiences, family problems, and psychiatric diagnoses. The
      prevalence of childhood family and psychiatric problems was high in both groups.

PMID- 8885595
TI  - Factors that mediate treatment outcome of sexually abused preschool children.
AB  - OBJECTIVE: The role of demographic, developmental, and familial mediating factors
      on treatment outcome of sexually abused preschool children was evaluated. METHOD:
      Sixty-seven sexually abused preschool children and their parents were evaluated
      shortly after disclosure of sexual abuse and then were provided with one of two
      treatment interventions. At the completion of treatment, the parents and their
      children were reevaluated. Parents completed the Child Behavior Checklist, the
      Child Sexual Behavior Inventory, and the Weekly Behavior Report to measure a
      variety of emotional and behavioral symptoms in children. Parents also completed
      the Beck Depression Inventory, the Family Adaptability and Cohesion Evaluation
      Scale-III, the Parent Emotional Reaction Questionnaire, the Parental Support
      Questionnaire, and the Maternal Social Support Index. Children completed the
      Preschool Symptom Self-Report to assess self-reported affective symptoms and the
      Battelle Developmental Inventory and the Peabody Picture Vocabulary Test to
      assess developmental level. RESULTS: Correlational analyses were conducted to
      analyze the relationships between the hypothesized mediating variables and the
      outcome measures at posttreatment across the two treatment groups. Multiple
      regression analyses were also performed. Both parental depression and parental
      emotional distress correlated significantly with several of the child outcome
      measures. Battelle scores were significantly negatively correlated with several
      outcome measures. Multiple regression analyses demonstrated that the Parent
      Emotional Reaction Questionnaire remained a highly significant predictor of
      treatment outcome. CONCLUSIONS: The findings indicate a strong correlation
      between parental emotional distress related to the abuse and treatment outcome in
      sexually abused preschool children, independent of the type of treatment
      provided. The findings indicate the importance of addressing parental distress
      related to the abuse in providing effective treatment to sexually abused
      preschool children.

PMID- 8885596
TI  - A psychiatric consultant's survival guide to the pediatric intensive care unit.

PMID- 8885597
TI  - Why is it so difficult?

PMID- 8885598
TI  - Standardization of the hospital record for osteopathic structural examination:
      Part 2. Effects of an educational intervention on documentation of palpatory and
      structural findings and diagnosis.
AB  - The purpose of this two-part study was to develop and test an instructional
      videotape for use in the osteopathic hospital setting; to standardize a procedure
      for documentation of palpatory and structural findings and diagnoses; and to
      examine the program's influence on the correlation of palpable and structural
      findings with a diagnostic impression of somatic dysfunction. To that end, the
      authors analyzed results of a survey of the medical records of 20 osteopathic
      training hospitals. Patients' charts were randomly pulled before and after house
      staff who performed admitting hospital examinations viewed an educational
      videotape. The videotape emphasized that the structural and palpatory screening
      examination should simply answer the question, "Is there a problem in the
      musculoskeletal system?" Chi-square analysis was used to evaluate the frequency
      of documentation of altered structural findings (structure, motion, tissue
      changes) and the diagnostic impression of somatic dysfunction and their
      correlation. Based on more than 300 reviewed charts, the authors found that the
      frequency of documentation of structural and palpatory examination was not
      significantly altered after house staff viewed the videotape. A sequence of
      hospital-based instruction in osteopathic principles and practices has been
      initiated at more than 50 osteopathic medical institutions, and the problems
      related to continuing medical education and clinical research in osteopathic
      medicine are discussed.

PMID- 8885599
TI  - Practice guidelines for the treatment of heart failure: a commentary on the facts
      you need to know. Agency for Health Care Policy and Research.
AB  - The federal Agency for Health Care Policy and Research has published its second
      set of guidelines in the field of internal medicine. These guidelines outline a
      comprehensive plan for the treatment of heart failure. They focus on the
      practical aspects of the management of patients with heart failure due to reduced
      left ventricular systolic performance (ejection fractions < 35% to 40%). They
      also offer expert opinion in the diagnosis and evaluation of heart failure and
      review clinical criteria for admission and discharge of these patients.
      Prevention of heart failure is a major focus of these current guidelines.

PMID- 8885600
TI  - Single photon emission computed tomography scanning in diagnosis of a rare pelvic
      avulsion fracture.
AB  - Avulsion fractures of the anterior inferior iliac spine are a relatively uncommon
      injury. Their diagnosis is usually made based on history, findings of the
      clinical examination, and standard roentgenograms. In the patient described, the
      diagnosis of avulsion of the anterior inferior iliac spine was made with the
      assistance of a single photon emission computed tomography scan, a relatively new
      diagnostic tool.

PMID- 8885601
TI  - Chest wall metastasis after percutaneous fine-needle aspiration biopsy.
AB  - Presented is a case of a chest wall metastasis due to tumor seeding along the
      needle tract from a percutaneous fine-needle aspiration biopsy (FNAB) of a lung
      carcinoma. At thoracostomy, the patient was found to have a chest wall lesion at
      the site of the FNAB that had been performed 4 months earlier. This relatively
      uncommon complication has been reported elsewhere, but its significance with
      respect to the management of lung lesions suspected to be malignant has not been
      defined. The authors maintain that FNAB may not be indicated in select patients.
      The application of this diagnostic modality should be considered individually on
      the basis of the patient's operative risk as well as the risk for having a
      primary lung carcinoma develop.

PMID- 8885602
TI  - Marching band injuries. A one-season survey of the University of Michigan
      Marching Band.
AB  - Clinical data were collected on injury occurrence to members of the University of
      Michigan Marching Band over the course of one season including a bowl game
      appearance. Band members were asked to fill out forms at the time of injury to
      gather pertinent information. The majority of the injuries were self-limiting.
      Included in this study was a total of 179 injuries, of which 153 (85.5%) involved
      the lower extremities. The authors provided a one-season injury survey of a
      collegiate marching band and made recommendations that may help to reduce and
      prevent future band-related injuries.

PMID- 8885603
TI  - Retrospective review of endoscopic plantar fasciotomy--1992 through 1994.
AB  - Endoscopic plantar fasciotomy is a rewarding procedure for both patient and
      surgeon. A vast majority of the patients have complete or near-complete
      resolution of heel pain at 6 months postoperatively. The procedure, however, is
      not without side effects and complications. This retrospective statistical study
      describes the postoperative side effects and complications of endoscopic plantar
      fasciotomy from 1992 to 1994. The procedure has been modified in an attempt to
      reduce several of the more commonly reported side effects.

PMID- 8885604
TI  - Evaluation and treatment of the infected foot in a community teaching hospital.
AB  - More inpatient hospital days are used for the care of diabetic foot infection
      than for any other diabetic sequela. Both the number of lower extremity
      amputations and the overall treatment cost of treating diabetic infections may be
      reduced by using a team approach in the care of the infected diabetic pedal
      wound. The authors propose an evaluation and treatment protocol of infected pedal
      ulcerations in an urban, community teaching institution when admitted to an
      established, multidisciplinary diabetic foot care team. The hospital course of
      111 patients admitted with a primary diagnosis of infected pedal ulceration are
      retrospectively reviewed. Results revealed an average-length hospital stay of 7.4
      days with a 96% limb-salvage rate. The authors suggest that in the treatment of
      the infected pedal wound, a diabetic foot care team with a well developed
      treatment protocol may yield a consistently favorable outcome and a cost
      effective hospital course.

PMID- 8885605
TI  - Subtalar joint motion and the relationship to lower extremity overuse injuries.
AB  - The purpose of this study was to determine if there was a difference between the
      subtalar joint ratio (transverse plane component to frontal plane component) in
      subjects with overuse symptoms in the foot compared with subjects with overuse
      symptoms in the leg and knee. Superior and posterior photographs were taken with
      the subtalar joint in pronation and supination while the subjects were in a
      seated position. The ratio of the transverse plane to frontal plane components of
      subtalar joint motion was calculated. A significant (p < 0.05) difference in the
      subtalar joint ratio existed between subjects with foot overuse symptoms and
      subjects with leg and knee overuse symptoms.

PMID- 8885606
TI  - Case presentation of calcaneonavicular coalition in monozygotic twins.
AB  - A case study of monozygotic twins with bilateral calcaneonavicular coalitions is
      presented. With the frequency of tarsal coalitions being approximately 1% to 2%
      and the frequency of monozygotic twins being 0.4%, it is a rare but predictable
      finding to see monozygotic twins with tarsal coalitions. This sheds additional
      light on the etiology of tarsal coalition that historically has been believed to
      be a defect in mesenchymal differentiation with indications of a genetic
      component. Despite the limited number of subjects used for various studies,
      tarsal coalitions have been considered to be an autosomal dominant defect with
      variable penetrance. In fact, inheritance of tarsal coalitions is more
      complicated than simple mendelian inheritance patterns and is likely to be a
      single error in a polygenic system. Because of this inheritance pattern, it is
      important to consider evaluating siblings and close family members of patients
      diagnosed with a tarsal coalition.

PMID- 8885607
TI  - Dermatofibrosarcoma protuberans. Salvaging quality of life using two approaches
      to treatment.

PMID- 8885608
TI  - Acute and chronic pedal boutonniere deformity.

PMID- 8885610
TI  - Health information systems for leprosy control programmes: a case for quality
      assessment.
AB  - A qualitative study was carried out aimed at checking the level of understanding
      and the actual use of the indicators recommended in leprosy control programmes by
      either the World Health Organization or the International Federation of Anti
      Leprosy Associations. Two successive questionnaires were sent to 268 leprosy
      control programme managers. The first one concerned information about the main
      characteristics of the programme, the information system in operation, and the
      data regarded as indispensable or useful for programme monitoring. The
      respondents to the first questionnaire (n = 64) proposed an extraordinarily wide
      range of indicators, mainly ill-defined. The respondents to the second
      questionnaire (n = 37) to whom a limited list of precisely defined indicators was
      submitted did not succeed in reaching a complete agreement on any of these
      indicators. Although the question of programme monitoring has been dealt with at
      an international level for years, there is an urgent need for a real agreement of
      international agencies and managers of leprosy control programmes on the
      indicators to be used. Programme managers in the field are obviously open to the
      idea of greater intervention by international organizations to improve data
      collection and to encourage standardization of computerized information systems.

PMID- 8885611
TI  - Origin of new leprosy cases during general surveys in relation to previous survey
      findings.
AB  - As part of the leprosy control activities in the area of Gudiyatham Thaluk,
      general surveys are done once every three to five years. The percentage of
      examination is about 90%. An analysis of all new cases registered for treatment
      between 1990-94 was done to study whether these cases had been examined in the
      previous general survey. Of the new cases detected and registered, 566 cases
      (32.6%) were not examined during the previous survey. The significance of these
      findings in relationship to cost-effectiveness of general surveys, case-detection
      methodology and possible continuing of transmission of leprosy are discussed.

PMID- 8885612
TI  - Gender differentials in the social impact of leprosy.
AB  - Prevalence rates of leprosy have reduced considerably in many states where
      multidrug therapy is in operation. However, reduction in prevalence alone is not
      sufficient as the social consequences of the diseases on the life of the patient
      are often severe and persist even after its cure. The present paper, therefore,
      investigates social impact with special reference to gender differentials. Data
      obtained from structured questionnaires (n = 606) is analysed for this purpose.
      It was observed that the initial delay in identifying the skin changes as the
      symptoms of the disease were higher for females (29 months) than males (24
      months). Even after identifying the symptoms, women were observed to depend
      exclusively on nonmedical treatment for a longer period (10 months) than males (6
      months). Upon starting the medical treatment females were observed to be more
      compliant than males, but the benefits of regularity appeared to be outweighed by
      the initial delay in starting medical treatment. The social impact on daily life
      was more severe for females than males as revealed by the isolation from daily
      activities, such as, restrictions on participation in familial functions,
      restrictions on touching children. The paper highlights implications of gender
      bias on detection and treatment, and suggests modifications for control
      programmes.

PMID- 8885613
TI  - Surgical reconstruction of leprotic foot-drop.
AB  - We have operated on 25 patients for correction of foot-drop due to leprosy from
      March 1992 to July 1994. The method used was circumtibial transfer of the
      tibialis posterior to the tendons of extensor hellucis longus and the extensor
      digitorum longus in the foot together with lengthening of the Achilles tendon.
      The results were satisfactory in 20 of these cases as judged by adequate
      restoration of heel-toe gait and of active dorsiflexion. The follow-up period
      ranged from 6 months to 2 years. Inadequate post-operative physiotherapy was the
      reason for unsatisfactory results in five cases.

PMID- 8885614
TI  - Pseudoepitheliomatous hyperplasia in trophic ulcers in leprosy patients. A 28
      case study.
AB  - Between 1984 and 1993, pseudoepitheliomatous hyperplasia developing in chronic
      ulcers were observed in 28 former Senegalese leprosy patients, which amounts to
      an annual frequency of 1.9 per 1000 ulcers. Correct diagnosis could only be made
      by histopathological examination of specimens taken from the depth of the lesion.
      Amputation was carried out on 17 patients and local excision on the other 10.
      Recurrence of growth was observed in 8 of the 10 patients treated by excision; in
      all of these 8 cases below knee amputation had to be subsequently performed. From
      our experience, it may be assumed that local excision should be carried out only
      in the case of small tumours. Since the aim of surgical procedure is to allow the
      patient to have physical autonomy, below knee amputation, followed by adaptation
      of prosthesis, should be the procedure chosen in the other cases.

PMID- 8885615
TI  - Cost-effective footwear for leprosy control programmes: a study in rural
      Ethiopia.
AB  - A randomized, controlled trial of commercially available canvas shoes was carried
      out in a rural area of Ethiopia. Subjects with deformed and anaesthetic feet,
      most with ulceration, were given either canvas shoes or plastazote/moulded shoes
      and followed up for one year. Seventy-five percent of subjects with ulcers who
      used canvas shoes had no ulcer at the end of the study, while no significant
      change was noted in the plastazote group. The durability and acceptability of the
      shoes were also examined. Clients in remote areas who have no access to an
      orthopaedic workshop, but who have anaesthetic feet, with or without deformity,
      should have access to canvas shoes with an MCR insole. Two pairs are needed per
      year at a cost of US$6.7 per pair.

PMID- 8885616
TI  - Two unusual nerve abscesses--lepromatous leprosy and pure neural leprosy: case
      reports.
AB  - We report two cases of nerve abscesses, one suffering from lepromatous leprosy
      (LL) and the other from tuberculoid neural leprosy. Neither had any signs of
      reactions. Both were untreated cases. Surgical nerve decompression and systemic
      prednisolone had resolved the nerve abscess in the first case, whereas the second
      one responded only to surgical nerve decompression. The unusual nature of
      clinical presentation of nerve abscess has been outlined.

PMID- 8885617
TI  - An unusual reaction to rifampicin in a once monthly dose.

PMID- 8885618
TI  - Pure neuritic leprosy of the supraorbital nerve.

PMID- 8885619
TI  - Development of life-threatening thrombocytopaenia in a patient on MDT and
      prednisolone.

PMID- 8885620
TI  - Delusional parasitosis in leprosy.

PMID- 8885621
TI  - Comment: 'silently arising clinical neuropathy' and extended indication of
      steroid therapy in leprosy neuropathy.

PMID- 8885622
TI  - Comment: newly 'registered' vs 'diagnosed' leprosy patients in the literature.

PMID- 8885623
TI  - Comment: current concepts in the surgical management of lagophthalmos in leprosy.

PMID- 8885624
TI  - Effect of seasonal host reproduction on host-macroparasite dynamics.
AB  - The impact of seasonal host reproduction on the population dynamics of host
      macroparasite interactions is considered. We modify the classic Anderson and May
      model so that parameters associated with host reproduction are periodic functions
      of time with a period corresponding to a year. This allows us to compare our
      findings with those already well documented. If, in the absence of any
      seasonality, a stable steady-state solution exists annual reproduction gives rise
      to stable annual population cycles. Moreover, the parameter domain for which
      there is stability is increased by the seasonality. However, if the life span of
      the free-living stages is reasonably long, and the continuous model has limit
      cycle solutions, complex behavior can be observed in the seasonally forced case.
      Results also indicate that if seasonal effects are ignored, regulation of the
      hosts by the parasite population is overestimated.

PMID- 8885626
TI  - Euphemisms, paraphrasings and other late summer diversions.

PMID- 8885625
TI  - Modeling triggered cardiac activity: an analysis of the interactions between
      potassium blockade, rhythm pauses, and cellular coupling.
AB  - It is known that under certain conditions, a combination of potassium channel
      blockade, sympathetic nervous activity, and pauses in sinus rhythm can increase
      the occurrence of cardiac arrhythmias. Although the arrhythmogenic interactions
      of these three factors are not completely understood, it is believed that the
      associated arrhythmias may be initiated by afterpotentials via a process that we
      refer to as propagated triggered activity. Using a two-cell computational model
      of ventricular action potential kinetics, we simulate nonuniform potassium
      blockade, sympathetic nervous activity, and pauses in sinus rhythm under
      conditions of hypokalemia. Under these conditions, the two-cell model suggests
      that (1) the arrhythmogenic interactions of potassium blockade and sympathetic
      nervous activity are highly dependent on heart rate; (2) triggered activity
      induced by potassium blockade would most likely occur during a pause in sinus
      rhythm; (3) during a sufficiently large pause in sinus rhythm, potassium blockade
      can induce triggered activity at normal levels of sympathetic activity; and (4)
      potassium blockade can increase the probability of triggered activity only if
      heart rate falls within a critical range. We also show that during pauses in
      sinus rhythm, two-cell triggering interactions between potassium blockade and
      sympathetic activity closely parallel the parametric displacement of the dynamic
      instability underlying the afterpotentials. Our results indicate that the
      behavior of the triggering mechanism studied here is consistent with that of
      pause-induced arrhythmias.

PMID- 8885627
TI  - Lessons in geography.

PMID- 8885628
TI  - Providing health care for the Russian-speaking patient.

PMID- 8885629
TI  - Hemoptysis in sarcoidosis: a case report.

PMID- 8885630
TI  - Does antecedent splenectomy alter the course of HIV infection?

PMID- 8885631
TI  - The detection of translocations using chromosome painting for monitoring exposure
      to potential genotoxicants.

PMID- 8885632
TI  - Point of view: who's on first? A reflection on euthanasia.

PMID- 8885633
TI  - Mid-course review: healthy Rhode Islanders 2000.

PMID- 8885634
TI  - Where there's smoke,....

PMID- 8885635
TI  - Doctor, "what about that article in the paper?".

PMID- 8885637
TI  - Physician assistant practice. The Nebraska Academy of Physician Assistants.

PMID- 8885636
TI  - Focus on musculoskeletal problems in medical school and residency training.

PMID- 8885638
TI  - Sphenopalatine ganglion block relieves symptoms of trigeminal neuralgia: a case
      report.
AB  - A 56 year old, white female with a diagnosis of trigeminal neuralgia,
      unresponsive to medical therapy, received a sphenopalatine ganglion block using
      bupivacaine 0.5%. A total of ten treatments were given. The patient remained pain
      free as of 30 months after initial treatment. This treatment appears to be
      effective and deserves further study.

PMID- 8885639
TI  - Low thoracic fracture dislocation of the spine.

PMID- 8885640
TI  - Pneumococcal vaccine.

PMID- 8885641
TI  - Ethanol in over-the-counter drugs.

PMID- 8885642
TI  - Hemoptysis in children.

PMID- 8885643
TI  - Multicultural issues in pediatric practice.

PMID- 8885644
TI  - Infantile spasms: current therapy and progress.

PMID- 8885645
TI  - Interpretation of routine chemistry tests in pediatrics.

PMID- 8885646
TI  - Anemia in preterm infants.

PMID- 8885647
TI  - Wilms tumor.

PMID- 8885648
TI  - Clindamycin.

PMID- 8885649
TI  - Congenital muscular torticollis.

PMID- 8885650
TI  - Replacement of the hip.

PMID- 8885651
TI  - Mechanistic and morphological origins of ultra-high molecular weight polyethylene
      wear debris in total joint replacement prostheses.
AB  - The mechanistic and morphological origins of microscopic wear debris generated
      from UHMWPE articular surfaces in total joint replacement prostheses are
      investigated in this study. It was found experimentally that the molecular chain
      structure at the articulating surface of UHMWPE undergoes a re-organization
      process due to strain accumulation caused by surface traction. This molecular re
      organization process creates a fibre-like surface texture that exhibits an
      anisotropic behaviour similar to a unidirectionally reinforced polymer composite.
      This composite responds to stresses favourably if loaded along the fibre axis but
      unfavourably if loaded off axis. Due to the very complex multi-axial
      motion/loading nature at the articular surfaces in total joint replacements, the
      stress tensors applied to each localized asperity contact area continuously
      change their directions and magnitudes. These changes in the localized stress
      field create an off-axis loading situation at each localized contact zone with
      respect to the orientation of the molecular chains. Depending on the off-axis
      angle, failure of the molecular structure occurs in three different ways: tensile
      rupture at very small off-axis angles, shear rupture at intermediate off-axis
      angles and transverse splitting at large off-axis angles. These failure
      mechanisms all produce similar fibre-like wear debris. However, the failure
      stresses differ significantly among the three modes. According to this molecular
      wear theory, the preferred polymer microstructure for optimal wear resistance
      would be a three-dimensionally strong network connected by covalent bonds between
      molecular chains. For UHMWPE, a three-dimensional molecular network can be
      created by radiation induced cross-linking. Experiments conducted on both gamma
      irradiated and unirradiated UHMWPE specimens using a linear wear machine and
      multi-axial joint simulators confirmed the validity of the molecular wear theory.

PMID- 8885652
TI  - The importance of multidirectional motion on the wear of polyethylene.
AB  - The development of a new hip simulator for the study of bearing materials used in
      total hip replacements has led to several findings which add important new
      information to the understanding of wear process of ultra-high molecular weight
      polyethylene, the most commonly used bearing material today for total joint
      replacements. Using this hip simulator which is capable of applying the
      physiological motion pathways occurring during gait to total hip components which
      are held in the correct anatomical position under the complex loading conditions
      of the hip in gait, the authors have shown that physiological motion pathways
      produce very different wear rates and morphology of the wear surface than
      unidirectional reciprocating pathways. Scanning electron microscopy studies show
      striking differences in the morphology of the wear surfaces of the polyethylene
      depending upon the relative motions of the components. Wear rates, surface
      morphology and particle debris generation consistent with clinical and retrieved
      studies are achieved when physiological conditions are simulated.

PMID- 8885653
TI  - Wear and morphology of ultra-high molecular weight polyethylene wear particles
      from total hip replacements.
AB  - The wear rate of ultra-high molecular weight polyethylene total hip replacement
      components is known to be influenced by various factors such as material and
      design. However, it is not known if these factors affect the size or morphology
      of the wear particles. The aim of this study was to compare the polyethylene wear
      particles from hip replacements of differing bearing materials and designs.
      Tissues were obtained at the revision surgeries of patients with surface
      replacements with titanium alloy or cobalt-chrome alloy femoral components up to
      51 mm in diameter, and stem-type hip replacements with cobalt-chrome or alumina
      ceramic femoral components that were 28 or 32 mm in diameter. The polyethylene
      particles were isolated following tissue digestion and density gradient
      separation, and then studied by scanning electron microscopy. A computerized
      image analysis system was used to measure the diameter and length of the
      particles. The majority of wear particles were submicron in diameter. No
      systematic differences in size and morphology were found between the groups in
      this study. The similarity in size and morphology of the wear particles suggested
      that the same basic wear mechanisms were occurring in these components.

PMID- 8885654
TI  - A three-axis hip joint simulator for wear and friction studies on total hip
      prostheses.
AB  - A three-axial, single-station hip joint simulator was designed and built for wear
      and friction studies on total hip prostheses. The design of the apparatus is
      described in detail. Continuous level walking is simulated. All three motion
      components, flexion-extension, abduction-adduction and internal-external
      rotation, are included. The motions are implemented electromechanically and the
      uniaxial load pneumatically. The load is measured continuously. For accurate
      measurement of wear, the apparatus has a loaded control joint, which also renders
      both the test and control joints self-centering, as they are loaded in series.
      The frictional torque of the test joint can be measured continuously throughout
      the wear test, which is an exceptional feature. Four tests of five million cycles
      each were completed using 32 mm diameter Co-Cr-Mo femoral heads and 5.6 mm thick,
      metal-backed, ultra-high molecular weight polyethylene acetabular cups as test
      specimens. Their wear and friction behaviour is described and discussed in
      relation to previous simulator studies and clinical observations. The lubricant
      was distilled water, maintained at body temperature. The wear of the cups was
      measured gravimetrically at intervals. The average wear rate was 3.9 mg/one
      million cycles, corresponding to 0.03 mm/year, and the average coefficient of
      friction was 0.01.

PMID- 8885655
TI  - Estimation of wear in total hip replacement using a ten station hip simulator.
AB  - The results of hip simulator tests on a total of 16 total hip joints, all of them
      22.25 mm Charnley designs, are presented. Wear at up to 6.75 million cycles was
      assessed by using a coordinate measuring machine. The results gave good agreement
      with clinical estimates of wear rate on the same design of joint replacement from
      a number of sources. Good agreement was also obtained when comparison was made
      with the published results from more sophisticated simulators. The major source
      of variation in the results was found to occur in the first million cycles where
      creep predominates. The results of this study support the use of this type of
      simplified simulator for estimating wear in a total hip prosthesis. The
      capability to test a significant number of joints simultaneously may make this
      mechanism preferable to more complex machines in many cases.

PMID- 8885656
TI  - Effect of counterface material on the characteristics of retrieved uncemented
      cobalt-chromium and titanium alloy total hip replacements.
AB  - A number of total hip components explanted at revision with bearing surfaces in
      either cobalt-chromium-molybdenum alloy or titanium-6% aluminium-4% vanadium
      alloy were examined and compared to contemporaneously manufactured but unused
      items; particular attention was paid to the bearing surfaces which were examined
      visually, by low-power microscopy, scanning electron microscopy (SEM), confocal
      microscopy, white light interferometry, laser profilometry and conventional
      stylus profilometry. The cobalt alloy heads maintained their surface finish well
      over periods up to 12 years. The titanium implants became badly damaged over much
      shorter periods although even badly scratched heads continued to meet the current
      standards for titanium alloy heads. Analysis showed that the damage to the
      titanium alloy heads was not a random but a well-defined process of scarring of a
      consistent size created by abrasion with small particles of bone. These damaged
      heads had the potential to wear the matching UHMWPE components rapidly creating
      large amounts of polymer debris. The finding that measurement of these damaged
      heads is within current standards raises concerns as to whether current standards
      incorporate fully the requirements for clinical performance.

PMID- 8885657
TI  - Wear in retrieved Charnley acetabular sockets.
AB  - One hundred and twenty-nine Charnley acetabular components were acquired at the
      time of revision surgery and a tribological investigation undertaken. The
      relative occurrence of pitting in the unworn and worn regions of the sockets
      suggest that most of the cement ingress occurs during the early part of the
      service life. The penetration depth of the explanted sockets was determined using
      the shadowgraph technique. Observation of the profiles in the wear planes suggest
      that, in general, the creep component was not a significant proportion of the
      overall change in the inner bore of the socket. Using weighted ordinary least
      squares regression, in which the intercept was not assumed to be zero, mean
      penetration and wear volume rates of 0.02 (SE = 0.02) mm/year and 55 (SE = 5)
      mm3/year, respectively, were recorded and are in agreement with other retrieval
      studies. In neither case was the intercept found to be significantly different
      from zero. A mean clinical wear factor, Kclinical, equal to 2.1 (SE = 0.2) x 10(
      6) mm3/N m was calculated which is considerably larger than that found in
      laboratory experiments which purport to reflect in vivo conditions. In this
      analysis, a significant positive intercept was observed [96 (SE = 36) mm3] and
      may be evidence of the small initial penetration due to creep reported in
      simulator experiments. A strong positive association between kclinical and the
      arithmetical mean roughness, Ra, of the femoral head was also demonstrated
      although the rate of change was not as great as that cited for laboratory
      experiments.

PMID- 8885658
TI  - An investigation into the origins of time-dependent variation in penetration
      rates with Charnley acetabular cups--wear, creep or degradation?
AB  - The total penetration of femoral heads into acetabular cups is achieved by a
      combination of long-term wear and early non-recoverable deformation or creep. The
      former is important in determining the total rate of production of polyethylene
      wear debris, recently implicated in the development of osteolysis and loosening,
      while the latter contributes to the overall penetration and the possibility of
      neck impingement in some designs of implants. Attention is drawn to the need to
      evaluate and to separate out these two physical processes in the assessment of
      clinical penetration rates. This is particularly important with more recent
      designs and combinations of materials, which are capable of operating with much
      reduced wear rates. Measurements of the penetrations of metallic femoral heads
      into polyethylene acetabular cups in 87 explanted Charnley hip arthroplasties
      from 85 patients are reported and assessed. The vast majority of the acetabular
      cups had been sterilized by gamma irradiation and the established shadowgraph
      technique was used to determine the penetrations. The average implantation time
      was 8.75 years, with a range from 0.2-18.6 years and the average age was 55
      years, covering the span 19-73 years. The influence of sterilization procedure,
      implantation time and patient age are considered. Assessments of the relative
      magnitudes of wear and non-recoverable deformation are made by different
      statistical techniques and compared with previously reported data from clinical
      and laboratory studies.

PMID- 8885659
TI  - Theory and practice of meniscal knee replacement: designing against wear.
AB  - This paper attributes the high rate of high-density polyethylene (HDP) wear in
      many knee prostheses to incongruity of their articular surfaces. The authors
      discuss the anatomical and kinematic features of the knee which have led most
      designers to choose incongruous surfaces and review the reasons for employing
      free bearings, analogues of the natural menisci, to provide congruity without
      restriction of movement. There are theoretical reasons against employing freely
      mobile bearing in the absence of a functioning anterior cruciate ligament (ACL)
      and the authors' experience has confirmed this limitation in practice. It is
      concluded that, in bicompartmental replacement, the movements of the meniscal
      bearing should be limited in the anteroposterior direction. For unicompartmental
      arthritis, an unconstrained bearing can be employed if, as is usually the case,
      all ligaments are intact.

PMID- 8885660
TI  - Metal-on-metal articulation for artificial hip joints: laboratory study and
      clinical results.
AB  - As wear is inevitable with artificial joint replacement, it has to be minimized
      to avoid possible aseptic loosening following osteolysis due to particle
      initiated foreign body reaction. Co-Cr-Mo-C alloys have a long history with only
      minimum wear when articulating with themselves. This investigation shows that the
      choice of the alloy has an effect on the wear rate of this articulation couple.
      Tribological studies in a screening device, a pendulum apparatus and a hip joint
      simulator showed a marked influence of the environment as well as the diameter of
      the implants with metal-on-metal articulation. A wear-resistant combination with
      low friction characteristics has been developed by using a wrought Co-Cr-Mo-C
      alloy and reducing the implant diameter to 28 mm. Clinical wear rates are
      comparable with laboratory data and demonstrate the potential of the metal-on
      metal articulation to solve the problem of wear-induced osteolysis of hip joint
      endoprostheses.

PMID- 8885661
TI  - Medical decisions at the end of life.

PMID- 8885662
TI  - The role of the social network in active euthanasia and physician-assisted
      suicide.
AB  - OBJECTIVE: To obtain insight into the involvement of a patient's social network
      in the process leading to the administration of euthanasia and assisted suicide
      (EAS). DESIGN: Descriptive, retrospective. METHOD: Data were collected by means
      of anonymous questionnaires sent to a random sample of 521 general practitioners
      (GPs) in the Province of North Holland and 521 GPs from the rest of the
      Netherlands and all 713 Dutch nursing home physicians (NHPs). The data were
      collected over the period 1986 to June 1990 inclusive. RESULTS: GPs and NHPs had
      discussions most often with the partner of the patient about the patient's
      request for EAS, the doctor's intention to administer EAS and the actual
      administering of EAS. According to both the GPs and the NHPs the social network
      practically always agreed with the doctor's decision to administer EAS. The
      persons who were most often present at the patient's bedside when EAS was
      administered were the patient's partner and children (29%). Often, especially in
      the cases of GPs, the decision not to report EAS was determined by the desire of
      relatives and/or the physician not to involve the relatives in a judicial
      inquiry. CONCLUSION: To a large extent the social network was involved in the
      patient's request for EAS, the doctor's intention to administer EAS and the
      actual administering of EAS. This seems to be important both for good decision
      making with regard to EAS and for helping relatives to come to terms with the
      loss of a dear one.

PMID- 8885663
TI  - An outbreak of Escherichia coli O157 and campylobacteriosis associated with
      contamination of a drinking water supply.
AB  - Stream water into which treated sewage discharged contaminated the public water
      supply of a Fife village with a population of about 1100. Of 765 residents and
      workers who reported illness 711 had gastrointestinal symptoms and 633 were
      defined as cases. Mains water analysis revealed high faecal coliform counts. An
      outbreak of Campylobacter and E coli 0157 infection was bacteriologically
      confirmed in eight and six people respectively. Two of the latter developed
      haemolytic uraemic syndrome. All affected individuals made full recoveries. Human
      normal immunoglobulin was offered to those aged between six months and 40 years
      of age and 618 individuals were immunised. Salivary tests four months after the
      incident confirmed that no Hepatitis A outbreak had occurred. In a follow-up
      questionnaire residents generally expressed happiness with the medical response
      to the incident although many reported that they still had worries. The two major
      medical issues which emerged from this outbreak were the importance of effective
      communications and the appropriateness of offering post-exposure human normal
      immunoglobulin.

PMID- 8885664
TI  - Model for the control of pediculus humanus capitis.

PMID- 8885665
TI  - Audit of school entry health assessments: to maximise efficient use of health
      personnel at school entry assessments at 5 years.
AB  - During the last 3 years in which doctors saw all school entrants, the decisions
      made about each child on examination were recorded and a protocol about decision
      making to support children with health needs was drawn up. In September 1994,
      school entry health care assessments by the school nurses were introduced. Having
      previously recorded the numbers in each school who required medical interest and
      support, it was possible to rationalise which schools should be the primary
      responsibility of the nurses, which should retain medical contact for all
      children and in which schools assessments should be shared. The outcomes in
      decision making after introducing nurse assessments were recorded in the same
      format as used by the doctors, so that the effect of passing responsibility to
      nurse colleagues could be assessed. The findings suggested that an equivalent
      number of children were referred to other services or selected for continuing
      review. However, the proportion of children whose needs were discussed with the
      headteacher without the children being selected for review was reduced. Issues to
      take forward were identified.

PMID- 8885666
TI  - Hearing impairment among young Chinese in a rural area.
AB  - To evaluate hearing levels in Chinese young people, audiometry was carried out at
      a rural village in Shandong Prefecture. The subjects were 282 healthy school
      children and students ranging in age from 7-17 y. All subjects were asked to
      complete a brief questionnaire on otological symptoms, personal histories and use
      of noisy playthings. Audiometric threshold testing was performed at the
      audiometric frequencies of 0.5, 1, 2, 4 and 8 kHz. Cluster analysis was used to
      estimate the associations between questions in the questionnaire and hearing
      impairment. Fifty-six subjects (20% subjects) were excluded from the normal
      groups. Twenty-two ears of the excluded subjects showed 4 kHz-dip and 38 ears
      showed high frequency hearing loss. An increased prevalence of hearing impairment
      was found when compared with young Japanese (1% from the nationwide school health
      survey) and with young Chinese in Shandong Prefecture (0.5%). In the
      questionnaire, 4 questions on dizziness, head trauma, aminoglycoside
      administration, and suspicion of Meniere's syndrome, were included in the cluster
      of hearing impairment. The cause of this hearing impairment was proposed to be
      the potentiating effects of aminoglycoside antibiotics and exposure to noise.

PMID- 8885667
TI  - The mental health of single homeless people in Northampton hostels.
AB  - Much research evidence about homelessness and health relates to large population
      centres with correspondingly large homeless populations. Such results may not
      necessarily apply to small towns such as Northampton. A local need was identified
      for information relating to health and access to health care for homeless people.
      Seventy five single, homeless people temporarily residing at open access hostels
      in Northampton were interviewed. The interviews covered: recent accommodation
      histories recent physical health mental health access to health care current
      social contacts, life style and aspirations The General Health Questionnaire
      (GHQ30) was administered to allow assessment of the levels of mental morbidity in
      the population studied. The results presented here relate to mental health
      issues. Current mental health problems were reported by 53% of the sample (40
      people); of these only 40% (16 people) were receiving treatment. Three people had
      been admitted to a psychiatric hospital within the past year. Using standard
      scoring, the GHQ30 identified as cases 72% (44) of the 61 homeless people who
      completed the GHQ. It was concluded that levels of mental morbidity were higher
      in the homeless group than would be expected in the general population. This
      finding, mirrors those of studies in larger population centres. The main form of
      access to mental health services appeared to be via hospital admission. Any GP
      treatment offered was likely to be medication. There was no mention of Community
      Psychiatric Nurse involvement in treatment or care. The results may indicate a
      significant level of unmet need for mental health intervention amongst the local
      homeless population.

PMID- 8885669
TI  - What impact do annual public health reports have?
AB  - Each district health authority is required to produce an annual report on the
      health of their population. Although they consume considerable resources, there
      is little evidence as to their impact on their intended audiences. We describe
      the results of a postal survey of how these reports are viewed by health
      authority and local government managers in one region. Eighty-nine out of 139
      responded (64%). Over half of the managers had read the reports in their
      entirety. Most were discussed by health authorities but few by relevant local
      government committees. There was some disagreement between directors of public
      health and other health authority managers about the impact of the reports on
      commissioning. The paper discusses the difficulties in evaluating the impact of
      annual public health reports. The survey reveals a fundamental disagreement about
      whether the intended audience should be health care purchasers or the public.
      This reflects an underlying tension about the role of public health and the
      debate about its independence.

PMID- 8885668
TI  - Improving the uptake of breast screening: one initiative in east London.
AB  - Attendance for breast screening in inner city areas is considerably below the
      national target. Previous research in Tower Hamlets, East London, indicated that
      a personal approach from the GP surgery could encourage women to attend.
      Practices were sent a list of women who had not responded to two invitations.
      Receptionists and health advocates were trained to enable them to contact women.
      The Breast Screening Mobile Unit remained on site so that women could make
      appointments to attend. Uptake for practices participating in the scheme was 55%,
      and 31% for those who did not participate.

PMID- 8885670
TI  - Hyperimmunoglobulinemia E, parasitic diseases and staphylococcal infection.

PMID- 8885671
TI  - Control of parasitic infections among school children in the peri-urban area of
      Botucatu, Sao Paulo, Brazil.
AB  - The prevalence of intestinal parasitosis was investigated in a primary school
      located in Rubiao Junior, a peri-urban district of Botucatu, Sao Paulo state,
      Brazil, in order to assess the effect of treatment and practical measures of
      prophylaxis in the control of parasitic infections among 7-to-18-year-old school
      children of a low socio-economic status. The first series of parasitological
      examinations included 219 school children, of which 123 (56.1%) were found to be
      infected with one or more parasite species. Eighty-four children carrying
      pathogenic parasites were submitted to various anti-parasitic treatment
      schedules. We re-evaluated 75 (89%) students after 4 to 6 months post
      chemotherapy. The results indicate that the combination of treatment with
      prophylactic measures has been successful in the control of parasitic infections,
      since reinfection rates were generally low (< or = 5.3%), except for Giardia
      lamblia infections (18.6%), and a marked reduction on the prevalence rates was
      observed with a significant percentage of cure (> or = 73.1%) in children
      infected with most parasite species. The reasons for the apparent failure in the
      control of infections caused by Hymenolepis nana and Strongyloides stercoralis
      are discussed.

PMID- 8885672
TI  - Antibody response to Salmonella typhi in human schistosomiasis mansoni.
AB  - Antibody response to Salmonella typhi O and H antigens was evaluated in 24
      individuals with either hepatointestinal or hepatosplenic schistosomiasis mansoni
      before and after typhoid vaccination, and compared with that of non-infected
      controls. Before vaccination, Schistosoma-infected patients showed a higher
      frequency of positive antibody to O antigen and the same frequency to H antigen
      when compared with that of healthy individuals. However, those with hepatosplenic
      schistosomiasis showed higher titres of antibody to H antigen than those with
      hepatointestinal disease or healthy individuals. Infected subjects, particularly
      those with hepatointestinal disease, showed a decreased response after typhoid
      vaccine. This diminished ability to mount an immune response towards typhoid
      antigens during schistosomiasis may interfere with the clearance of the bacteria
      from blood stream and, therefore, play a role in the prolonged survival of
      salmonella as observed in some patients with chronic salmonellosis associated
      with schistosomiasis.

PMID- 8885673
TI  - Production and characterization of monoclonal antibodies to the EDTA extract of
      Leptospira interrogans, serovar icterohaemorrhagiae.
AB  - Monoclonal antibodies (MABs) were produced against an ethylenediaminetetraacetate
      (EDTA) extract of Leptospira interrogans serovar icterohaemorrhagiae being
      characterized by gel precipitation as IgM and IgG (IgG1 and IgG2b). The EDTA
      extract was detected as several bands by silver staining in SDS-PAGE. In the
      Western blot the bands around 20 KDa reacted with a monoclonal antibody, 47B4D6,
      and was oxidized by periodate and was not digested by pronase, suggesting that
      the determinant is of carbohydrate nature. Immunocytochemistry, using colloidal
      gold labeling, showed that an EDTA extract determinant recognized by monoclonal
      antibody 47B4D6, is localized under the outer envelope of serovar
      icterohaemorrhagiae. The MAB raised against the EDTA extract was not able to
      protect hamsters from lethal challenge with virulent homologous leptospires.

PMID- 8885674
TI  - Safety evaluation of SPf66 malaria vaccine in Brazil.
AB  - The frequency and description of side effects secondary to the subcutaneous
      application of SPf66 malaria vaccine and placebo are reported for each dose of
      application in the participants of the vaccine efficacy trial in Brazil. Side
      effects evaluated two hours after each application were detected in 8.0%, 30.2%
      and 8.8%, for the 1st, 2nd and 3rd dose, respectively, in the SPf66 group, and in
      7.0%, 8.5% and 2.9% in the placebo group. Local reactions such as mild
      inflammation, nodule and pain or erythema frequently accompanied by pruritus were
      the most common reactions detected in both groups (3.8%, 29.1% and 8.5% in the
      SPf66 group and 4.0%, 7.6% and 2.5% in the placebo group). Among vaccinees, local
      side effects after the 2nd dose were more frequent in females. Systemic side
      effects were expressed mainly through general symptoms referred by the
      participants and were most frequent after the 1st dose in both groups (4.3% in
      the SPf66 group and 3.0% in the placebo group). Muscle aches and fever were
      referred by few participants. No severe adverse reactions were detected for
      either dose of application or group.

PMID- 8885675
TI  - Parotid enlargement due to adenovirus infection in patient with human
      immunodeficiency virus infection.
AB  - The authors report a case of adenovirus-induced enlargement of the parotid gland
      involving a patient infected with human immunodeficiency virus (HIV). Physical
      examination revealed good general condition, no fever and bilateral enlargement
      of the parotid region, which was of increased consistency and slightly tender to
      palpation. Histological examination of the parotid gland demonstrated a slight
      periductal lymphomononuclear inflammatory infiltrate with the presence of focal
      points of necrosis. Tests to determine the presence of fungi and alcohol-acid
      resistant bacilli were negative. Immunohistochemistry for cytomegalovirus, herpes
      simplex, HIV p24 antigen and adenovirus showed positivity only for adenovirus in
      the epithelial nuclei of numerous gland ducts. This is the third case of this
      type reported in the literature, indicating the importance of including
      adenovirus in the differential diagnosis of this condition.

PMID- 8885676
TI  - Inflammatory response against Trypanosoma cruzi parasitised cells from adrenal
      vein and myocardium in chronic Chagas' disease.

PMID- 8885681
TI  - Non occlusive ileocaecocolic intussusception caused by caecum cancer--case
      report.
AB  - A case of ileocaecocolic intussusception caused by a caecum carcinoma is
      presented. The authors stress the peculiarity of clinical manifestation, without
      intestinal obstruction despite the presence of a big abdominal mass involving
      vessels and bowel, revealed by CT scanning and angiography. Endoscopy was not
      able to identify the nature of the lesion. Laparotomy performed with the idea to
      find a mesenchymal neoplasia, permitted to achieve the diagnosis.

PMID- 8885682
TI  - Abdominal aortic aneurysm combined with a second intraabdominal non vascular
      disease--a clinical study and surgical treatment.
AB  - The surgical tactics in cases of aneurysm of the infrarenal abdominal aorta and a
      second intraperitoneal operative procedure are not uniform in the literature and
      still remain a matter of debate. In 170 aneurysms of the abdominal aorta there
      were 18/170 (10.5%) other co-existent surgical non-vascular diseases as follows:
      Thirteen cases with symptomatic or asymptomatic cholecystopathy, one case with
      abdominal hernia, three cases with Ca of the colon and one case with Ca of the
      liver. In 9 cases, the aneurysm and the gallbladder were removed concomitantly,
      in 3 cases only aneurysmectomy was carried out due to cardiopulmonary problems,
      of which in two cholecystectomy was carried out in a second stage. In one case
      with cholecystitis, the gallbladder was removed and aneurysmectomy followed one
      month after. Aneurysmectomy and sigmoidectomy were carried out in one case and in
      a second similar case sigmoidectomy preceded followed by aneurysmectomy 6 months
      later. In one case aneurysmectomy and restoration of the abdominal hernia was
      performed concomitantly, while two more cases, one with liver lobectomy and
      another with orthosigmoidectomy due to Ca. No one of the above patients presented
      with any infection of the graft or other postoperative complication. No other
      complications were noted during a follow-up period of 19 months. The one stage
      operation management of infrarenal abdominal aortic aneurysm and a second (intra
      abdominal) surgical procedure is feasible if appropriate care is given to the
      technical details and due consideration to the rules of antisepsis, without
      affecting surgical morbidity and mortality of the patient.

PMID- 8885683
TI  - Body mass index (BMI) is a reliable index to estimate obesity as a risk factor
      for deteriorating health.
AB  - The objective of this study was to find out what index is appropriate to evaluate
      obesity, by measuring body fat using bioelectrical impedance analysis (BIA).
      Subjects in this study were 74 women, aged 44 to 73, living in Tokushima
      prefecture. The means +/- standard deviation (SD) of Broca index, Body mass index
      (BMI) and body fat were 103 +/- 14.3%, 23.0 +/- 2.8 kg/m2 and 28.1 +/- 5.5%,
      respectively. In addition, their clinical data such as blood pressure, glutamate
      pyruvate transaminase activity (GPT), triglycerides (TG) and fasting blood sugar
      (FBS) were within normal ranges. When compared with correlation between obesity
      indices (Broca index or BMI) and height, there was a negative correlation between
      Broca index and height (= -0.447). Furthermore, the number of obese subjects
      estimated by Broca index was less than that of obese subjects estimated by BMI.
      Although both Broca index and BMI showed higher correlations with body fat
      estimated by BIA, BMI (r = 0.927) showed a higher correlation compared to that of
      Broca index (r = 0.875). These results suggest that BMI is a reliable index to
      evaluate the body fat.

PMID- 8885684
TI  - Localization and imaging of human plasmacytoma xenografts in severe combined
      immunodeficiency mice by a new murine monoclonal antibody, anti-HM1.24.
AB  - We have examined the localization in the tumor of anti-HM1.24, a murine
      monoclonal antibody which is specific for human plasma cell-associated antigen.
      The biodistribution and imaging were compared in severe combined immunodeficiency
      mice bearing human plasmacytoma (RPMI 8226) xenografts after intravenous
      injection of radiolabeled anti-HM1.24. The mean tumor uptake of 1 microCi of 125I
      labeled anti-HM1.24 was 2.98% injected dose per g of tissue (%ID/g) at day 1 and
      increased to 5.50% ID/g at day 4, whereas tumor uptake values of control IgG was
      always less than 1.36% ID/g. The tumor localization indices ranged between 2.35
      and 6.03 at day 1 to 4 after injection. Anti-HM1.24 showed no evidence of
      targeting to normal tissues except a splenic uptake, however, splenic targeting
      was abolished by the blocking of Fc receptors in the reticuloendothelium. In most
      cases, tumor-to-tissue ratios were greater than 2 at day 4, indicative of tumor
      selectivity for anti-HM1.24. Radioimaging with 10 microCi of 131I-labeled anti
      HM1.24 showed that 25% of the total-body count were localized in the tumor and
      the tumors could be visualized without subtraction techniques at day 4.
      Furthermore, the penetration and binding of anti-HM1.24 to the tumor cells were
      confirmed by autoradiographic studies. These findings indicate that anti-HM1.24
      is a potent agent for detection and targeting of human plasmacytoma.

PMID- 8885686
TI  - Prevention of posttransfusion hepatitis by screening with second-generation anti
      HCV antibody and clinical features of HCV infection.
AB  - After adaptation of the second-generation anti-hepatitis C virus (HCV) test, the
      incidence of post-transfusion hepatitis (PTH) resulted in 5.2% (11/208), which
      was significantly lower than that 10.5% (22/209) demonstrated by screening donor
      blood for C100-3 antibody. The 11 cases of PTH, three were classified as definite
      PTH and the other were as suspected one. Of two cases with definite PTH and two
      cases with suspected PTH, their blood samples after transfusion became positive
      for HCV-RNA, and three cases of those showed a second peak of alanine
      aminotransferase (ALT) more than 4 weeks after operation. On the other hand, of
      seven cases containing one definite PTH, their blood samples after transfusion
      became negative for HCV-RNA, and five cases of those showed ALT peaks within 4
      weeks after operation, and returned to normal levels of ALT thereafter. Moreover,
      in cases of definite PTH, the periods of surgery and anesthesia were longer and
      the volume of bleeding was much more during operation than in cases of suspected
      PTH, although the differences were not statistically significant. These findings
      suggested that cases of PTH include those of transient liver disease attributable
      to surgery as well as those of HCV infection. In 11 cases of PTH, we consider
      that 2 cases is true PTH, because these are HCV-RNA positive and have second peak
      more than 4 weeks after operation and 5 cases is questionable by clinical date.
      Thus new diagnostic criteria should have established.

PMID- 8885685
TI  - Potentiation by apamin of histamine-stimulated catecholamine biosynthesis and
      tyrosine hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells.
AB  - The effects of small-conductance Ca2(+)-activated K+ channel (SK channel)
      blocker, apamin, on histamine-stimulated catecholamine biosynthesis and tyrosine
      hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells were
      investigated. Histamine (10(-10)-10(-6) M) stimulated [14C]catecholamine
      biosynthesis from [14C]tyrosine (but not from [14C]DOPA). Apamin (10(-6) M)
      enhanced the histamine-stimulated catecholamine biosynthesis, which was abolished
      by omission of extracellular Ca2+. Histamine increased the intracellular free
      Ca2+ concentration ([Ca2+]i), and this increased [Ca2+]i was potentiated by the
      presence of apamin. The increase in histamine-stimulated catecholamine
      biosynthesis with apamin was sensitive to the inhibitors of protein kinase C and
      Ca2+/calmodulin dependent protein kinase. Apamin increased the histamine-induced
      phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in
      catecholamine biosynthesis. These results suggest that in cultured bovine adrenal
      chromaffin cells the inhibition of SK channel results in potentiation of
      catecholamine biosynthesis and tyrosine hydroxylase phosphorylation induced by
      histamine and that these stimulatory effects may result from the activation of
      protein kinase C and Ca2+/calmodulin-dependent protein kinase through an increase
      in [Ca2+]i.

PMID- 8885687
TI  - A study on simplification of the Standard Language Test of Aphasia (SLTA).
AB  - The Standard Language Test of Aphasia (STLA) was developed for classification and
      evaluation of severity of aphasia of Japanese speakers in 1975. Now it has become
      the most reliable test for patient with aphasic condition in Japan. However, the
      test involves many tasks and assessment is rather complicated. A simplified
      display of aphasic conditions was created by means of statistical analysis of the
      features of types of aphasia in order to reduce time and labor involved in SLTA
      for bed side use. Data were collected from 198 patients, including 40 patients
      with Broca aphasia (17 severe and 23 moderate cases), 64 patients with Wernicke
      aphasia (28 severe and 36 moderate cases) and 94 patients with global aphasia (68
      severe and 26 moderate cases). A test with simplfied aphasia pattern involved
      naming objects for daily use (represented by pictures), pronunciation of words
      written in Kanji (Chinese characters) and in Kana (syllabary), pronunciation of
      single Kana, dictation of single Kana (oral presentation), repeating simple words
      presented by the examiner, dictation of words to be written in Kanji (oral
      presentation), matching words in Kana and a picture (pointing), writing words in
      Kanji (represented by pictures), writing words in Kana (represented by pictures),
      and auditory comprehension of words.

PMID- 8885688
TI  - Mutagenicity of chemicals produced from sodium dodecylbenzenesulfonate by
      treatment with ozone and ultraviolet irradiation.
AB  - The interaction of formaldehyde and glyoxal produced from linear
      dodecylbenzenesulfonate (DBS) in aqueous solution after simultaneous treatment
      with ozone and ultraviolet (UV) irradiation and the effect of DBS on the
      mutagenic activity of formaldehyde and glyoxal were investigated. The
      decomposition of DBS in aqueous solution resulted in the formation of the
      mutagens formaldehyde and glyoxal as intermediate products after the simultaneous
      treatment for 4 hr. Therefore, the aqueous solution containing decomposed DBS
      after the treatment for 4 hr was mutagenic for Salmonella typhimurium strains
      TA100 and TA104 in the presence and absence of S9 mix. However, the mutagenic
      activity was greater than the sum of the mutagenic activity of formaldehyde and
      glyoxal formed from DBS. The aqueous solution mixed with formaldehyde and glyoxal
      did not increase the mutagenicity above the sum of the mutagenic activity in the
      presence or absence of DBS. Furthermore, DBS at concentrations of 2.0
      micrograms/plate or less did not affect the mutagenicity of the mixtures
      containing formaldehyde and glyoxal. In addition, there was little bacteriocidal
      effect of the mixed solution on the mutagenicity test strains. These results
      suggest that unidentified mutagenic intermediate products were produced from DBS
      after simultaneous treatment with ozone and UV irradiation for 4 hr.

PMID- 8885689
TI  - Immunohistochemical localization of surfactant protein A in N-bis (2
      hydroxypropyl) nitrosamine-induced lung tumors in rats.
AB  - Surfactant protein A (SP-A) is most abundant protein associated with pulmonary
      surfactant which is synthesized by alveolar type II cells in the alveoli. In this
      study, we localized SP-A in experimentally induced pulmonary hyperplasias and
      tumors in rats, by immunohistochemistry. When rats were given a single
      intraperitoneal injection of N-bis (2-hydroxypropyl) nitrosamine (BHPN) followed
      by exposed to mixture gases of O3 and NO2, hyperplastic alveolar type II cells
      stained with the antibody against SP-A were located in the alveolar walls near
      the alveolar ducts. Adenomas and adenocarcinomas were stained with the anti-SP-A
      antibody in the lung parenchyma. These immunohistochemical findings suggested
      that the lung tumors induced in rats treated with BHPN and additionally exposed
      to mixture gases of O3 and NO2 are derived from mainly alveolar type II cells.

PMID- 8885690
TI  - Morphological changes of human pulmonary-artery endothelial cells after 12-hours
      hypothermic storage in organ-preservation solutions.
AB  - Pulmonary endothelial cells are known to be fundamental for lung preservation and
      one of the most serious limiting factors observed during transplantation is the
      stress to which these cells are subjected. On this premise, strenuous efforts
      should be made to select and employ the preservation solution best able to
      prolong ischemia time and thus prevent cytotoxic effects. The aim of this study
      was to identify the solution with minimum toxicity on endothelial cells. For this
      purpose, we analysed the noxious effect of solutions such as Euro Collins (ECS),
      Belzer (UWS) and Low-potassium Dextran (LPD) on endothelial cells after 12 hours
      of incubation at 10 degrees C. For each solution, we examined the modifications
      produced on the nuclei, mitochondria and cellular wall of human pulmonary-artery
      endothelial cells by transmission electron microscopy and recorded the results on
      an ultrastructural grading scale. As regards morphological alterations
      incompatible with cell life, the most cytotoxic solution proved to be ECS. UWS
      and LPD, on the contrary, appeared to preserve cells relatively well, and no
      perceptible difference was observed between the two solutions. In conclusion, it
      is interesting to note that although ECS is widely used for lung preservation,
      the results of our study indicate that a 12 hours at 10 degrees C in this
      solution may exert adverse effect on pulmonary endothelial cells.

PMID- 8885691
TI  - Recent developments with neuropeptide Y receptor antagonists.

PMID- 8885692
TI  - The transmitter-gated channels: a range of receptor types and structures.

PMID- 8885693
TI  - Application of in situ microdialysis to measure metabolic and vascular responses
      in adipose tissue.

PMID- 8885694
TI  - 5-HT4 receptor agonists and bladder disorders.

PMID- 8885695
TI  - The ageing bladder in urinary tract disorders.

PMID- 8885696
TI  - Festschrift in honour of Professor Sir Colin Dollery.

PMID- 8885697
TI  - GABAc receptors: relatively simple transmitter -gated ion channels?
AB  - The inhibitory neurotransmitter, GABA, activates a variety of receptors in all
      areas of the CNS. Two major subtypes of GABA receptors are well known: (1) GABAA
      receptors are ligand-gated Cl- channels that consist of a heteromeric mixture of
      protein subunits forming a pentameric structure, and (2) GABAB receptors couple
      to Ca2+ and K+ channels via G proteins and second messengers. Here, Graham
      Johnston discusses evidence for a third major subclass of GABA receptors. GABAC
      receptors appear to be relatively simple ligand-gated Cl- channels with a
      distinctive pharmacology, in that they are not blocked by bicuculline and not
      modulated by barbiturates, benzodiazepines or neuroactive steroids. Compared with
      GABAA receptors, GABAC receptors are activated at lower concentrations of GABA
      and are less liable to desensitization. In addition, their channels open for a
      longer time. The pharmacology of these novel subtypes of GABA receptors may yield
      important therapeutic agents.

PMID- 8885698
TI  - Exosites: their current status, and their relevance to the duration of action of
      long-acting beta 2-adrenoceptor agonists.
AB  - The four beta 2-adrenoceptor agonists, clenbuterol, bambuterol, formoterol and
      salmeterol, are all long-acting bronchodilators, that have distinct mechanisms
      for their extended durations of action. Various theories have been put forward in
      an attempt to explain these mechanisms. In this respect, there is strong evidence
      for the existence of specific additional binding sites (exosites) for salmeterol
      and related compounds, and that exosites exist on non-ligand recognition regions
      of the beta 2-adrenoceptor protein. Here, Robert Coleman and colleagues compare
      and contrast the profiles of action of these long-acting beta 2-adrenoceptor
      agonists, particularly as they relate to the role of exosites.

PMID- 8885699
TI  - Phosphodiesterase 4 and tolerance to beta 2-adrenoceptor agonists in asthma.
AB  - beta 2-Adrenoceptor agonists provide a mainstay in the treatment of asthma
      worldwide. However, despite their ability to provide symptomatic relief, chronic
      or repeated exposure to beta 2-adrenoceptor agonists does not resolve asthmatic
      inflammation, because of the rapid development of tolerance by pro-inflammatory
      and immune cells of the lung. The prevailing belief is that tolerance to the so
      called non-bronchodilator actions of beta 2-adrenoceptor agonists is largely
      attributable to direct receptor desensitization mediated by G protein receptor
      coupled kinases and/or cAMP-dependent protein kinase. Here, Mark Giembycz
      suggests another, largely ignored, explanation for beta 2-adrenoceptor
      desensitization that is based on the accelerated degradation of cAMP by
      phosphodiesterase.

PMID- 8885700
TI  - Joint United Nations programme on HIV/AIDS (UNAIDS). HIV and infant feeding: an
      interim statement.

PMID- 8885701
TI  - Cholera outbreaks. Ineffective control measures.

PMID- 8885702
TI  - Poliomyelitis outbreak.

PMID- 8885703
TI  - Adherence of Streptococcus uberis to bovine mammary epithelial cells and to
      extracellular matrix proteins.
AB  - Adherence of an encapsulated (UT 101) and a non-encapsulated (UT 102) strain of
      Streptococcus uberis to a bovine mammary epithelial cell line (MAC-T) and to
      extracellular matrix proteins (ECMP) including fibronectin, collagen and laminin
      was investigated. S. uberis was co-cultured at 4 degrees C with MAC-T cell
      monolayers. Both strains of S. uberis adhered to MAC-T cells. However, the non
      encapsulated strain of S. uberis adhered better to MAC-T cells than the
      encapsulated strain. Preincubation of MAC-T cells with lipoteichoic acid (LTA)
      and/or treatment of S. uberis with antibodies directed against the carboxyl
      terminal half of type 24 M protein reduced adherence of both strains of S. uberis
      to MAC-T cells. Adherence to ECMP was measured by incubating bis-carboxyethyl
      carboxyfluorescein acetomethyl ester (BCECF-AM) labelled S. uberis in 96-well
      plates coated with fibronectin, collagen or laminin. Both strains adhered to
      ECMP, however, the encapsulated strain adhered better to ECMP than the non
      encapsulated strain. Results of this investigation demonstrated that both strains
      of S. uberis evaluated were capable of adhering to bovine mammary epithelial
      cells and to ECMP. Adherence of S. uberis to mammary epithelium may be an
      extremely important mechanism in the establishment and progression of bovine
      intramammary infections.

PMID- 8885704
TI  - Diagnosis of rabbit haemorrhagic disease (RHD) and European brown hare syndrome
      (EBHS) by indirect sandwich polyclonal ELISA.
AB  - The establishment of two indirect sandwich polyclonal ELISAs for the virological
      diagnosis of rabbit haemorrhagic disease (RHD) and European brown hare syndrome
      (EBHS) is described. Each assay uses rabbit and guinea pig antisera raised to RHD
      or EBHS purified virus particles. The tests are sensitive and specific, but cross
      reactions between rabbit haemorrhagic disease virus (RHDV) and European brown
      hare syndrome virus (EBHSV) are observed. Most rabbit liver homogenates
      identified as RHDV-positive by ELISA do not haemagglutinate human red blood cells
      at room temperature.

PMID- 8885705
TI  - Susceptibility of hares and rabbits to the European brown hare syndrome virus
      (EBHSV) and rabbit haemorrhagic disease virus (RHDV) under experimental
      conditions.
AB  - The European brown hare syndrome virus (EBHSV) and the rabbit haemorrhagic
      disease (RHDV) virus were inoculated in hares and rabbits to discover whether the
      homologous and heterologous host could be infected. The aims were to confirm the
      results of previous studies that showed the existence of antigenic differences
      between these two viruses, and also to define the role attributed to the hare in
      transmission to rabbits of a disease, EBHS, initially mistaken for RHD. During
      the trials, clinical symptoms and pathological lesions were noted, and
      virological and serological analysis were conducted, using specific tests set up
      for both diseases. The hares infected with EBHSV died of an acute form of EBHS,
      whereas the rabbits remained healthy. The low serological response in these
      rabbits towards the EBHSV did not protect them against RHDV. Similarly, hares
      inoculated with RHDV remained healthy and showed a low anti-RHDV antibody titre
      but died when challenged with EBHSV.

PMID- 8885706
TI  - Rinderpest and other animal morbillivirus infections: comparative aspects and
      recent developments.
AB  - The genus morbillivirus presently comprises measles virus of man, rinderpest
      virus (RPV), peste des petits ruminants virus (PPRV), and canine distemper virus
      (CDV). 'Emerging' morbilliviruses, such as phocid distemper virus (PDV) of seals,
      dolphin (DMV) and porpoise morbillivirus (PMV) have probably been present for a
      long period of time and outbreaks are possibly related to introduction into a
      highly susceptible population and/or be the result of interspecies transmission.
      In this review some comparative aspects of morbillivirus infections, particularly
      with respect to rinderpest and canine distemper viruses, are presented. Topics
      include pathogenesis, epidemiology, molecular phylogeny, diagnosis and
      prophylaxis. Recent developments in molecular biology have created tools which
      have enabled us to achieve a better understanding of morbillivirus infections at
      the nucleic acid level ('molecular epidemiology') while recombinant DNA
      technology has allowed new bivalent recombinant vaccines with improved heat
      stability to be produced.

PMID- 8885708
TI  - The association between tumour necrosis factor-alpha, interleukin-6 and
      microbiological findings in the synovial fluid of aborted and neonatal calves.
AB  - Tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) were detected
      in the intra-carpal synovial fluids collected from aborted and recently dead
      young calves. Five out of seven TNF-alpha positive joint fluids were
      bacteriologically positive and two were sterile. Only one out of 20 TNF-alpha
      negative joint aspirates was infected (P = 0.0014). Sixteen of the synovial fluid
      samples were examined for the presence of IL-6. In 12 samples IL-6 was detected,
      six of which were bacteriologically contaminated. Four out of the 16 samples were
      IL-6 negative. These findings indicated the possible association between TNF
      alpha and the intra-articular inflammatory processes in young calves, which in
      the present study were either found in combination with or without IL-6.

PMID- 8885707
TI  - An immunohistochemical method of detecting Mycoplasma species antigens by use of
      monoclonal antibodies on paraffin sections of pneumonic bovine and caprine lungs.
AB  - Lung samples from pneumonic lesions in cattle and goats, naturally or
      experimentally infected with strains of the Mycoplasma mycoides cluster, were
      fixed in formalin and embedded in paraffin. An immunohistochemical technique
      using monoclonal or polyclonal antibodies was performed on tissue sections in
      order to detect Mycoplasma antigens. Four monoclonal antibodies (MAbs), one (2A3)
      raised against M. mycoides ssp. mycoides small colony (SC) and large colony (LC),
      two (1D3 and 5E5) against M. mycoides ssp. capri, and one (5A10) against M.
      bovis, were used. A range of polyclonal antibodies, raised to the individual
      subspecies of the M. mycoides cluster, and one to Pasteurella haemolytica, was
      also used. The MAb 2A3 showed positive immunostaining in lung sections from
      cattle and goats naturally and experimentally infected with M. mycoides ssp.
      mycoides SC and LC, but not with pneumonic lesions of cattle and goats due to
      other members of the M. mycoides cluster, M. bovis or Pasteurella spp. The MAb
      1D3 showed immunostaining in lung sections from goats naturally and
      experimentally infected with M. mycoides ssp. capri, but again not with pneumonic
      lesions caused by other members of the M. mycoides cluster, M. bovis or
      Pasteurella spp. The MAb 5E5 immunoreacted in sections from pneumonic lesions
      from all animals infected with one of the three M. mycoides cluster subspecies
      used in the study, but not with M. bovis or Pasteurella infected tissue.
      Immunoreaction was mainly found in the cell debris around necrotic areas, as well
      as in macrophages, neutrophils and epithelial cells. The localization of antigens
      of the M. mycoides cluster using polyclonal antisera followed basically the same
      pattern as that obtained with the monoclonals. However, a wide cross reactivity
      was found between different antisera and relatively high background
      immunostaining was also seen, especially in necrotic areas. The results suggest
      that immunohistochemical methods using monoclonal antibodies are useful tools for
      the diagnosis and study of the pathogenesis of pneumonia caused by the
      Mycoplasmas of the M. mycoides cluster.

PMID- 8885709
TI  - No rabies detected in voles and field mice in a rabies-endemic area.
AB  - Brain samples were collected from 514 voles and wild mice in Estonia, and
      examined for rabies. The samples were tested with antigen ELISA, and 8.6% of them
      additionally by virus isolation assay. The results were negative. Our data show
      that in areas of north-eastern Europe, where rabies is endemic in raccoon dogs
      and red foxes, populations of smaller mammals may remain free of rabies.

PMID- 8885710
TI  - Magnitude versus parity in numerical judgements: event-related brain potentials
      implicate response conflict as the source of interference.
AB  - When subjects make 'odd/even' and 'low/high' decisions about digits, information
      about the digit's magnitude can interfere with the decision about the digit's
      parity. The present experiment used a psychophysiological approach to examine
      whether this interference arises at the level of response processing. Subjects
      performed a choice-reaction time task involving low/high and odd/even judgements
      about the digits 2 through 9. The data point to a response locus for the
      interference effect with the size of the effect being dependent on the ease with
      which magnitude information can be used to prime the appropriate response. This,
      in turn, is influenced by the 'naturalness' of the mapping between magnitude and
      response hand as well as by the distance of a digit to the low/high cut-point.

PMID- 8885711
TI  - From cognition to biomechanics and back: the end-state comfort effect and the
      middle-is-faster effect.
AB  - Consistent preferences for particular types of movement suggest criteria for
      movement selection. These can be important when, as is usually the case,
      infinitely many movements allow a task to be achieved. The experiments reported
      here were designed to identify the source of a strong preference observed in
      earlier object-manipulation studies. In those earlier studies, subjects usually
      grabbed objects to be moved from one location to another in a way that afforded a
      comfortable final posture rather than a comfortable initial posture (the end
      state comfort effect). The comfortable final state usually allowed the forearm to
      be at or near the middle of its range of motion on the pronation-supination
      dimension. The hypothesis tested here was that the end-state comfort effect
      stemmed from an expectation that movements can be made more quickly in the middle
      of the pronation-supination range than at either extreme. To test this
      hypothesis, we asked subjects, in the first experiment, to perform a handle
      rotation task that demanded little or no precision and so no need to make rapid
      to-and-fro homing-in movements near the end of the rotation. Half the subjects
      did not show the end-state comfort effect, in contrast to all previous studies,
      where all subjects showed the effect. An incidental finding of the first
      experiment was that handle rotations that ended at or near the end of the range
      of motion took longer than handle rotations that ended at or near the middle of
      the range of motion. To test the latter result more carefully, we asked subjects,
      in Experiments 2 and 3, to oscillate the forearm as quickly as possible, either
      in the supination part of the forearm rotation range, in the middle part of the
      range, or in the pronation part of the range. As predicted, oscillation
      frequencies were highest in midrange, and this was true for both hands. The
      results as a whole have implications for the relation between cognitive
      psychology and biomechanics, and for human factors.

PMID- 8885712
TI  - The role of congruency and pleasantness in odor-induced taste enhancement.
AB  - Although odorants and tastants are perceived by two different senses, the rated
      intensity of a tastant may increase if an odorant is added. The size of the odor
      induced taste enhancement is said to depend on the perceptual similarity between
      the tastant and the odorant, and on the task instruction which affects subjects'
      working concepts of attribute categories. It is investigated whether congruency
      or pleasantness (halo-effects) can replace perceptual similarity in accounting
      for odor-induced taste enhancement. Sweetness intensity, pleasantness, and degree
      of congruency are determined for three sucrose/odorant combinations. Odor-induced
      enhancement is found only for congruent mixtures (sucrose/strawberry and
      sucrose/lemon). In addition, highly congruent mixtures are more pleasant than
      expected under additivity. The pleasantness judgments for incongruent
      combinations (sucrose/ham) follow a subtractive rule. The congruency ratings can
      account for a significant part of the pleasantness ratings, but not for the
      degree of sweetness enhancement. Also, the pleasantness ratings are not related
      to the degree of enhancement. Therefore, congruency or pleasantness ratings
      cannot replace similarity ratings in accounting for odor-induced taste
      enhancement.

PMID- 8885713
TI  - Signaling mechanisms mediating synapse formation.
AB  - Recent experiments have begun to decipher the molecular dialog that mediates
      differentiation at sites of synaptic contact between neurons and their targets.
      It had been hypothesized that the protein agrin is released by axon terminals at
      embryonic neuromuscular junctions and binds to a receptor on the myofiber surface
      to trigger postsynaptic differentiation. Now a genetic 'knockout' experiment has
      confirmed the essential role of agrin in signaling between developing nerve and
      muscle. A second 'knockout' has shown that the muscle-specific receptor tyrosine
      kinase MuSK is a critical element in the agrin-induced signaling cascade.
      Additional results suggest that MuSK may comprise a portion of the agrin
      receptor.

PMID- 8885714
TI  - Cell proliferation control in Drosophila: flies are not worms.
AB  - The development of organs during animal development requires the allocation of
      appropriate numbers of cells to each part of the structure. Yet in Drosophila the
      patterns of cell proliferation can be quite different from one individual to the
      next, and in fact can be altered experimentally without altering final
      morphology. The developing pattern seems to control proliferation, rather than
      the other way around. Even though the pattern of proliferation is variable, there
      is some order to it. A recent paper shows that small clusters of cells in
      developing cell populations are in mitotic synchrony, but that the synchrony is
      transient. What is the significance of this mitotic synchrony?

PMID- 8885715
TI  - Craniofacial defects in AP-2 null mutant mice.
AB  - AP-2 is a recent significant addition to the list of transcription factors that
      have been demonstrated by targeted gene disruption to be essential for normal
      development. Two recent reports of AP-2 null mutant mice indicate that AP-2 holds
      a key position in the network of genes and proteins controlling developmental
      pattern and morphogenesis, and that it is particularly important for development
      of the cranial region and for midline fusions.

PMID- 8885716
TI  - Myelin mutants: model systems for the study of normal and abnormal myelination.
AB  - Spontaneous mutations that perturb myelination occur in a range of species
      including man, and together with engineered mutations have been used to study
      disease, normal myelination and axon/glial inter-relationships. Only a minority
      of the currently defined mutations have an apparently simple pathogenesis due to
      lack of a functional protein. Mutations in the myelin basic protein gene lead to
      a lack of protein, resulting in changes in the structure of myelin, which can be
      rescued by transgenic complementation. The pathogenesis of autosomal dominant and
      X-linked mutations affecting either oligodendrocytes or Schwann cells is more
      complex. Point mutations may act in a dominant negative manner and gene dosage is
      clearly linked to phenotypic change. Mutations in regulatory genes, such as those
      encoding transcription factors, can also disturb myelination by selected cell
      types. Other less-well studied and unexpected consequences of myelin mutations,
      such as seizures in mutations affecting genes expressed in Schwann cells and
      axonal changes associated with dysmyelination, are also considered. With the
      major developments in gene mapping and cloning it is now relevant to study
      mutations in a variety of species with the real prospect of defining their
      molecular basis. Examples are given of unusual, but potentially useful,
      uncharacterized mutations in dog and bovine.

PMID- 8885717
TI  - Aging mechanisms in fruit files.
AB  - Genetic analysis of Drosophila has provided evidence in support of two proposed
      evolutionary genetic mechanisms of aging: mutation accumulation and antagonistic
      pleiotropy. Both mechanisms result from the lack of natural selection acting on
      old organisms. Analyses of large numbers of files have revealed that mortality
      rates do not continue to rise with age as previously thought, but plateau at
      advanced ages. This phenomenon has implications both for models and for
      definitions of aging, and may be explained by the evolutionary theories. The
      physiological processes and genes most relevant to aging are being identified
      using Drosophila lines selected in the laboratory for postponed senescence.
      Oxidative stress and insufficient metabolic reserves/capacity may be particularly
      important factors in limiting the fruitfly lifespan. Genes which exhibit aging
      related changes in expression are now being identified. Transgenic files are
      being used to analyze the mechanisms of such aging-related gene expression, and
      to test the effects of specific genes on aging and aging-related deterioration.

PMID- 8885718
TI  - Invertebrate gerontology: the age mutations of Caenorhabditis elegans.
AB  - Ageing is a complex phenomenon which remains a major challenge to modern biology.
      Although the evolutionary biology of ageing is well understood, the mechanisms
      that limit lifespan are unknown. The isolation and analysis of single-gene
      mutations which extend lifespan (Age mutations) is likely to reveal processes
      which influence ageing. Caenorhabditis elegans is the only metazoan in which Age
      mutations have been identified. The Age mutations not only prolong life, but also
      confer a complex array of other phenotypes. Some of these phenotypes provide
      clues to the evolutionary origins of these genes while others allude to
      mechanisms of lifespan-extension. Many of the Age genes interact and share a
      second common phenotype, that of stress resistance. Rather than invertebrate
      ageing being determined by a 'clock mechanism', a picture is emerging of ageing
      as a non-adaptive process determined, in part, by resistance to intrinsic stress
      mediated by stress-response genes.

PMID- 8885719
TI  - Epigenetic factors and midbrain dopaminergic neurone development.
AB  - In the mammalian brain dopamine systems play a central role in the control of
      movement, hormone release, emotional balance and reward. Alteration of
      dopaminergic neurotransmission is involved in Parkinson's disease and other
      movement disorders, as well as in some psychotic syndromes. This review
      summarises recent findings, which shed some light on signals and cellular
      interactions involved in the specification and maturation of the dopaminergic
      function during neurogenesis. In particular we will focus on three major issues:
      (1) the differentiation of dopaminergic neurones triggered by direct contact with
      the midbrain floor plate cells through the action of sonic hedgehog; (2) the
      neurotrophic factors acting on dopaminergic neurones; and (3) the role of target
      striatal cells on the survival and the axonal growth of developing or grafted
      dopaminergic neurones.

PMID- 8885720
TI  - X-linked agammaglobulinemia (XLA): a genetic tyrosine kinase (Btk) disease.
AB  - X-linked agammaglobulinemia is a heritable immunodeficiency disease caused by a
      differentiation abnormality, resulting in the virtual absence of B lymphocytes
      and plasma cells. The affected gene encodes a cytoplasmic protein tyrosine
      kinase, Bruton's agammaglobulinemia tyrosine kinase, designated Btk. Btk and the
      other family members, Tec, ltk and Bmx, contain five regions, four of which are
      common structural and functional modules that are found in other signaling
      proteins. Mutations affect all domains of the gene, but amino acid substitutions
      seem to be confined to certain regions. More than 150 unique mutations have been
      identified and are collected in a mutation database, BTKbase. Here we discuss the
      three-dimensional structural implications of such mutations and their putative
      functional role. Of special interest are mutations affecting the pleckstrin
      homology domain, as Btk is the only disease-associated protein so far reported to
      carry mutations in this particular module.

PMID- 8885721
TI  - Nuclear transplantation in mammals: remodelling of transplanted nuclei under the
      influence of maturation promoting factor.
AB  - Whilst the role of Maturation or M-phase Promoting Factor (MPF) as a universal M
      phase regulator is well documented, much less attention has been paid to its role
      in nuclear transplantation experiments and especially to its influence upon
      remodelling of transplanted nuclei. There is currently wide acceptance that
      successful nuclear transplantation using differentiated nuclei is possible only
      in a cytoplasmic environment that is capable of inducing rapid nuclear de
      differentiation to a pronuclear-like form. In this review our purpose is firstly,
      to outline the conditions under which such remodelling can be induced, and
      secondly, to extend the debate to include a consideration of whether complete
      nuclear remodelling is an absolute necessity for clonal development.

PMID- 8885722
TI  - Asymmetry--where evolutionary and developmental genetics meet.
AB  - The mechanisms responsible for the fine tuning of development, where the wildtype
      phenotype is reproduced with high fidelity, are not well understood. The
      difficulty in approaching this problem is the identification of mutant phenotypes
      indicative of a defect in these fine-tuning control mechanisms. Evolutionary
      biologists have used asymmetry as a measure of developmental homeostasis. The
      rationale for this was that, since the same genome controls the development of
      the left and right sides of a bilaterally symmetrical organism, departures from
      symmetry can be used to measure genetic or environmental perturbations. This
      paper examines the relationship between asymmetry and resistance to
      organophosphorous insecticides in the Australian sheep blowfly, Lucilia cuprina.
      A resistance gene, Rop-1, which encodes a carboxylesterase enzyme, also confers a
      significant increase in asymmetry. Continued exposure of resistant populations to
      insecticide has selected a dominant suppressor of the asymmetry phenotype.
      Genetic evidence indicates that the modifier is the L. cuprina Notch homologue.

PMID- 8885723
TI  - Antibiotic resistance: origins, evolution and spread. Ciba Foundation Symposium,
      16-18 July 1996, London.

PMID- 8885724
TI  - Dietary vitamin E prophylaxis and diabetic embryopathy: morphologic and
      biochemical analysis.
AB  - OBJECTIVE: In this study we sought to determine whether dietary supplementation
      with vitamin E, a known antioxidant, would reduce the incidence of diabetic
      embryopathy in an in vivo rat model. STUDY DESIGN: Eighty-day-old Sprague-Dawley
      rats were assigned to one of five groups: two control groups (groups 1 and 2) and
      three diabetic groups (groups 3, 4, and 5). One group of controls (group 2) and
      one group of diabetic rats (group 4) received dietary supplements of vitamin E
      (440 mg/day). The other three groups (groups 1, 3, and 5) received a normal diet
      only. Group 5 received insulin therapy to control glucose levels. On day 6 of
      gestation diabetes was induced in groups 3, 4, and 5 with streptozotocin (65
      mg/kg). Animals were killed on day 12; embryos were examined for size, protein
      content, evidence of malformations, and superoxide dismutase activity. RESULTS:
      In both groups (groups 3 and 4) of diabetic rats the mean blood glucose level
      than was significantly higher in controls. Insulin-treated animals (group 5) had
      glucose levels that were comparable to those of controls. The unsupplemented
      diabetic group had a neural tube defect rate of 21.48% +/- 9.6% (percentage of
      neural tube defects per rat) and a resorption rate of 21.37% +/- 20.39%
      (percentage of resorptions per rat) as compared with rates in the supplemented
      diabetic group of 6.92% +/- 4.08% and 2.17% +/- 3.74%, respectively (p < 0.01).
      Groups 1, 2, and 5 had similar neural tube defect rates (6.63% +/- 5.0%, 5.01% +/
      4.87%, and 3.55% +/- 5.92%, respectively. Vitamin E levels, measured by high
      performance liquid chromatography, were significantly higher in maternal serum
      and embryos in the supplemented groups (p < 0.001) than in controls. Superoxide
      dismutase activity was reduced in the diabetes groups and was not affected by
      vitamin E therapy. CONCLUSIONS: Supplementation with the antioxidant vitamin E
      confers a significant protective effect against diabetic embryopathy and may
      potentially serve as a dietary prophylaxis in the future. We postulate that this
      protective effect is mediated by a reduction in the oxidative load induced by
      hyperglycemia.

PMID- 8885725
TI  - L-arginine reverses the adverse pregnancy changes induced by nitric oxide
      synthase inhibition in the rat.
AB  - OBJECTIVE: Inhibition of nitric oxide synthase with N omega-nitro-L-arginine
      methyl ester (L-NAME) induces a preeclampsia-like syndrome of hypertension,
      proteinuria, intrauterine growth restriction, and renal glomerular capillary
      endothelial lesions in pregnant rats. We attempted to reverse these changes with
      late-pregnancy administration of L-arginine. STUDY DESIGN: Sprague Dawley rats
      with timed pregnancies received infusions of either saline solution (n = 12)
      (group SC) or L-NAME (n = 12) (group LC) (160 mg/kg per day) on gestational day
      10 through term. On gestational day 16 half of the saline solution group (group
      SA) and half of the L-NAME group (group LA) received L-arginine (21 mg/kg per
      day) through delivery. Systolic blood pressures were determined via tail cuff on
      days 10, 16, and 21. Pup weights were assessed at delivery, serum and urine were
      collected and analyzed for nitrites and nitrates, and renal tissue was processed
      for histologic examination. Data were analyzed with the one-way analysis of
      variance and the Newman-Keuls test for multiple comparisons. RESULTS: In the L
      NAME-treated animals L-arginine significantly lowered systolic blood pressure at
      late pregnancy (125 +/- 2.42 vs 153 +/- 3.0 mm Hg) (p < 0.01), increased mean pup
      weight (5.6 +/- 0.11 gm in group LA vs. 5.0 +/- 0.02 gm in group LC) (p < 0.001),
      decreased the degree of proteinuria (2+ vs trace), and decreased the proportion
      of injured glomeruli (7% vs 64%) (p < 0.001). CONCLUSIONS: Lesions induced by
      chronic inhibition of endothelium-derived nitric oxide synthesis (hypertension,
      intrauterine growth restriction, proteinuria, renal glomerulus injury) are
      reversed by treatment with L-arginine. These findings lend support to the
      potential for use of nitric oxide donors in the treatment and prevention of
      preeclampsia.

PMID- 8885726
TI  - Management of the symptomatic placenta previa: a randomized, controlled trial of
      inpatient versus outpatient expectant management.
AB  - OBJECTIVE: Our purpose was to determine the safety, efficacy, and costs of
      inpatient and outpatient management of symptomatic placenta previa. STUDY DESIGN:
      Fifty-three women with the initial diagnosis of placenta previa at 24 to 36
      weeks' gestation who required hospitalization for vaginal bleeding were
      stabilized and then randomized to receive either inpatient or outpatient
      expectant management. Twenty-seven inpatients were placed at bed rest with
      minimal ambulation, received weekly corticosteroids until 32 weeks of gestation,
      and underwent ultrasonographic examination at 2-week intervals to assess fetal
      growth and placental location. Twenty-six outpatients were discharged home after
      > or = 72 hours of hospitalization. Each week they also received corticosteroids,
      until 32 weeks' gestation, and ultrasonographic evaluations. Outpatients with
      recurrent bleeding were readmitted for evaluation. All subjects who reached 36
      weeks' gestation with persistent placenta previa underwent amniocentesis. When
      fetal lung maturity was present, cesarean delivery was electively performed.
      RESULTS: There were insignificant differences between inpatients and outpatients
      for mean age, parity, race, type of previa (complete or partial), number of prior
      vaginal bleeding episodes, and initial hemoglobin value. The mean estimated
      gestational age at enrollment was 29.1 +/- 3.1 (SD) weeks for inpatients and 29.9
      +/- 3.1 weeks for outpatients. In eight patients the placenta was found to no
      longer cover the internal os by 36 weeks' gestation. There were seven patients in
      each group who did not complete the protocol for initial treatment assignment.
      The average estimated gestational age at delivery for the inpatients was 34.5 +/-
      2.4 weeks and 34.6 +/- 2.3 weeks for the outpatients (p = 0.90), whereas the mean
      birth weights were 2413.7 +/- 642.7 gm and 2607.8 +/- 587.1 gm, respectively (p =
      0.28). Thirty-three patients (62.3%) had recurrent episodes of bleeding, with 26
      requiring expeditious cesarean delivery. Four (14.8%) inpatients and one (3.7%)
      outpatient required blood transfusion (p = 0.67). There was no difference in
      neonatal morbidity (defined as the presence of respiratory distress syndrome,
      intracranial hemorrhage, or culture-proved sepsis) between the two groups
      (relative risk 1.16, 95% confidence interval 0.66 to 2.02). There were no
      neonatal deaths. The mean number of maternal hospital days differed significantly
      between the two groups: inpatients required an average of 28.6 +/- 20.3 days and
      outpatients remained hospitalized for an average of 10.1 +/- 8.5 days (p <
      0.0001). Cost analysis based on maternal hospital days reveals a net savings of
      +15,080 per patient if women with symptomatic placenta previa initially diagnosed
      before 37 weeks' gestation are treated as outpatients. CONCLUSIONS: For selected
      patients, outpatient management of symptomatic placenta previa appears to be an
      acceptable alternative to traditional conservative expectant inpatient
      management.

PMID- 8885727
TI  - Interleukin-6 concentrations in cervical secretions identify microbial invasion
      of the amniotic cavity in patients with preterm labor and intact membranes.
AB  - OBJECTIVE: The objectives of this study were to determine whether cytokine levels
      in cervical secretions were increased in the presence of microbial invasion of
      the amniotic cavity in patients with preterm labor and intact membranes and to
      relate concentrations to cytokine levels in amniotic fluid, cervicovaginal
      microflora, and the presence of chorioamnionitis. STUDY DESIGN: Cervical
      secretions were sampled immediately before amniocentesis in 92 patients admitted
      for preterm labor with singleton pregnancies and intact membranes. Amniotic fluid
      was cultured and the following cytokines were measured in amniotic fluid and
      cervical secretions: interleukin-1 beta, interleukin-1 receptor antagonist, tumor
      necrosis factor-alpha, and interleukin-6. The cervicovaginal microflora and
      placentas (n = 42) were also analyzed. RESULTS: A total of 19.56% (18/92) of the
      amniotic fluid cultures had positive results. All the cytokines tested showed
      significantly higher levels in cervical secretions in the presence of
      intraamniotic infection. There were significant relationships between the
      concentrations of interleukin-6 and interleukin-1 receptor antagonist in amniotic
      fluid and cervical secretions. A concentration of interleukin-6 in cervical
      secretions > 410 pg/ml had a sensitivity of 66.8% and a specificity of 90.5% and
      a relative risk of 7.7 for intraamniotic infection, higher than the other
      cytokines tested. There were no relationships between the presence of bacterial
      vaginosis and cervicovaginal pathogens and cervical cytokine levels. In the
      presence of chorioamnionitis, cervical concentrations of interleukin-6 and
      interleukin-1 receptor antagonist were significantly increased in spite of
      negative amniotic fluid culture results. CONCLUSION: The measurement of
      interleukin-6 in cervical secretions may help to noninvasively identify
      intraamniotic infection among pregnancies with preterm labor and intact
      membranes.

PMID- 8885729
TI  - Risk of Down syndrome and any clinically significant chromosome defect in
      pregnancies with abnormal triple-screen and normal targeted ultrasonographic
      results.
AB  - OBJECTIVE: Our purpose was to study prospectively the use of ultrasonographic
      biometry to refine the risk estimates for both Down syndrome and any clinically
      significant chromosome defect in women with abnormal biochemical triple-screen
      results. STUDY DESIGN: Ultrasonographic biometry and anatomic survey were
      performed on study and control cases. Expected values for humerus, femur,
      combined humerus plus femur lengths, and abdominal circumference were generated
      on the basis of biparietal diameter obtained from a normal group. Threshold
      observed/expected values of each measurement for screening for Down syndrome and
      clinically significant chromosome defects were determined with receiver-operator
      characteristic curves. By stepwise logistic regression analysis the optimal
      screening parameters, including nuchal thickness, for detection of Down syndrome
      and clinically significant chromosome defect were determined. Risk tables for
      chromosome anomalies were developed on the basis of ultrasonography and triple
      screen values. RESULTS: Of 1034 cases at risk for Down syndrome (risk > or =
      1/270) or trisomy 18 on the basis of triple-screen results, there were 11 cases
      of Down syndrome, 1 of trisomy 18, and 17 clinically significant chromosome
      defects. Abnormal nuchal thickness or observed/expected humerus length < 0.92 was
      the most sensitive parameter for Down syndrome detection. Abnormal nuchal
      thickness or observed/expected combined femur and humerus length < 0.90 was the
      most sensitive for significant chromosome defects. With abnormal biometry or
      anatomy the Down syndrome risk was 8 of 127 versus 1 of 753 in normals, odds
      ratio 50.4 (95% confidence interval 6.4 to 90.2), p < 0.00001, and the risk of
      significant defects was 11 of 90 versus 6 of 830 in normals, odds ratio 19.3 (95%
      confidence interval 6.4 to 60.5), p < 0.00001. In a pregnancy with a 1 in 270
      triple-screen risk for Down syndrome, normal biometric and anatomic results
      reduce the risk to 1 in 2100. CONCLUSION: Normal ultrasonographic anatomy and
      biometry significantly reduces the risk of both Down syndrome and any significant
      chromosome defects in pregnancies with abnormal triple-screen results.

PMID- 8885728
TI  - Dietary polyunsaturated fatty acid prevents malformations in offspring of
      diabetic rats.
AB  - OBJECTIVE: The purpose of the current study was to determine whether a dietary
      source of arachidonic acid could serve as a pharmacologic prophylaxis to obviate
      the teratogenic effects of hyperglycemia. STUDY DESIGN: Eighty-day-old Sprague
      Dawley rats were mated, and after conception were randomly allocated to five
      groups: two groups were nondiabetic normal controls and three groups had diabetes
      experimentally induced with streptozocin. Of the two control groups, one was fed
      a normal diet (group 1) and the other group (group 2) received a normal diet and
      1.0 ml of safflower oil, a polyunsaturated fatty acid known to increase serum
      arachidonic acid levels. In the three diabetic groups (groups 3, 4, and 5)
      glucose levels were allowed to remain > 350 mg/dl by withholding daily insulin
      therapy. Group 3 received a normal diet without supplementation; group 4 received
      a normal diet plus normal saline solution sham feedings, whereas group 5 received
      a normal diet supplemented with 1.0 ml of safflower oil. The oral agents (normal
      saline solution and polyunsaturated fatty acid) were administered with a
      tuberculin syringe. RESULTS: Diabetic rats not receiving insulin therapy and
      receiving normal diets produced offspring with malformation rates of 20% compared
      with control rates of 4.8%. Supplemental normal saline solution or safflower oil
      given orally to controls did not alter the growth or malformation rates. These
      rates were similarly unaffected in the diabetic rats receiving oral
      supplementation of normal saline solution. However, with safflower oil
      supplementation to diabetic rats the incidence of neural tube defects was
      decreased from 20.0% to 7.6% (p < 0.0001). An inverse relationship was observed
      between the malformation rate and the serum arachidonic acid level: 17.83 (SD
      5.84 micrograms/ml) in the nondiabetic controls, with a malformation rate of
      4.8%, versus 14.18 (SD 2.58 micrograms/ml) in the diabetic rats, with a
      malformation rate of 20.0% (p < 0.05). With safflower oil supplementation serum
      levels of arachidonic increased from 14.18 +/- 2.58 micrograms/ml to 19.99 +/-
      7.99 micrograms/ml (p < 0.05); this was associated with a concomitant decline in
      the malformation rate. CONCLUSION: These data demonstrate that diabetic
      embryopathy is associated with a deficiency state in essential fatty acid,
      corroborating our previous in vitro findings. Furthermore, the use of a dietary
      polyunsaturated fatty acid that specifically increases arachidonic levels
      significantly reduced the incidence of diabetic embryopathy. These findings may
      serve as a basis for developing strategies of pharmacologic prophylaxis against
      diabetes-induced congenital malformations.

PMID- 8885730
TI  - Elevated amniotic fluid interleukin-6 levels at genetic amniocentesis predict
      subsequent pregnancy loss.
AB  - OBJECTIVE: Our purpose was to determine the proportion of pregnancy loss after
      genetic amniocentesis that is related to preexisting subclinical intrauterine
      inflammation. STUDY DESIGN: We accessed our bank of stored second-trimester
      amniotic fluid and maternal serum samples obtained from women undergoing genetic
      amniocentesis at our institution from 1988 to 1995 (N = 11,971). Interleukin-6
      levels were measured by enzyme-linked immunosorbent assay in samples from every
      case resulting in spontaneous postprocedure loss (excluding fetal aneuploidy and
      anomalies) within 30 days after the procedure (n = 66) and from 66 normal control
      women delivered at term and matched for year of test, gestational age, maternal
      age, and indication for amniocentesis. RESULTS: Mean maternal serum interleukin-6
      levels were the same in each group (0.02 +/- 0.07 ng/ml for cases and 0.06 +/-
      0.25 ng/ml for controls, p = 0.45). Mean amniotic fluid interleukin-6 levels were
      higher in cases (4.0 +/- 13.1 ng/ml) than in controls (0.5 +/- 0.7 ng/ml, p =
      0.04). The higher mean amniotic fluid interleukin-6 levels in the cases resulted
      from the inclusion of eight very high values (> or = 3 SD or > or = 2.5 ng/ml).
      When these samples were excluded, the means and range of values were the same in
      each group (0.4 +/- 0.4 ng/ml for cases and 0.5 +/- 0.7 ng/ml for controls, p =
      0.58). Twelve percent (8/66) of the cases and 3% (2/66) of the controls had
      amniotic fluid interleukin-6 levels > or = 2.5 ng/ml (p = 0.048, odds ratio 4.1,
      95% confidence interval 1.0 to 31.2). Although the overall correlation between
      maternal serum and amniotic fluid interleukin-6 levels was good (r = 0.50, p <
      0.002), only one of the eight cases would have been identified by a maternal
      serum interleukin-6 level > or = 3 SD above the mean (> or = 0.8 ng/ml).
      CONCLUSION: Analysis of our complete unselected group of postamniocentesis
      pregnancy losses indicates that up to 12% may result from preexisting subclinical
      intrauterine inflammation. This inflammation is most likely localized and may not
      be identified by a maternal serum interleukin-6 level before the procedure.

PMID- 8885731
TI  - Oral terbutaline after parenteral tocolysis: a randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: Our purpose was to determine whether oral terbutaline, used after
      successful intravenous tocolysis, will prolong pregnancy and prevent recurrent
      preterm labor. STUDY DESIGN: After successful intravenous tocolysis, 203 women
      with preterm labor at 24 weeks' to 34 weeks 6 days' gestation were randomized to
      terbutaline (5 mg orally, every 4 hours) or placebo until 37 weeks' gestation.
      Women with recurrent preterm labor were treated with intravenous magnesium
      sulfate; if tocolysis was successful, they continued with the initial study
      medication. The primary outcome was the percentage delivered of their infants
      within 1 week of beginning oral tocolytic therapy. Latency, recurrent preterm
      labor, and maternal and neonatal outcomes were also assessed. RESULTS: Pregnancy
      outcome data were available in 200 women. There were no differences seen between
      the two groups in the incidence of delivery at 1 week (18% vs 24%, 95% confidence
      interval 0.44 to 1.29). In addition, there were no differences regarding median
      latency, mean gestational age at delivery, or the incidence of recurrent preterm
      labor (20% vs 16%, 95% confidence interval 0.64 to 2.71). Post hoc evaluation of
      96 women enrolled before 32 weeks' gestation suggested pregnancy prolongation
      with maintenance oral terbutaline (p < 0.01). CONCLUSIONS: Maintenance oral
      terbutaline therapy initiated at 24 weeks' to 34 weeks 6 days' gestation after
      successful parenteral tocolysis is not associated with pregnancy prolongation or
      a reduction in the incidence of recurrent preterm labor.

PMID- 8885732
TI  - The clinical efficacy of oral tocolytic therapy.
AB  - OBJECTIVE: Our purpose was to determine whether maintenance oral tocolytic
      therapy after preterm labor stabilization decreases uterine activity, reduces the
      rate of recurrent preterm labor and subsequent preterm birth, or improves
      neonatal outcome. STUDY DESIGN: Women with documented idiopathic preterm labor
      stabilized with acute tocolytic therapy were randomized to three groups: placebo,
      terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours.
      Patients and providers were blinded to group assignment. All subjects were
      enrolled in a comprehensive system of preterm birth prevention that included
      preterm labor education, weekly clinic visits, home uterine contraction
      assessment, daily phone contact, and 24-hour perinatal nurse access. RESULTS: Of
      the 248 patients who were randomized, 39 were delivered before discharge and 4
      were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72
      terbutaline, and 65 magnesium. The terbutaline group had significantly more side
      effects than the placebo group did. All groups had otherwise similar perinatal
      outcomes when confounding variables were controlled for. Overall, the three
      groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of
      15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal
      length of stay of 6.3 days. CONCLUSIONS: Maintenance oral tocolytic therapy did
      not decrease uterine activity, reduce the rate of recurrent preterm labor or
      preterm birth, or improve perinatal outcome. Overall improvement in perinatal
      outcome may be achieved with a comprehensive program of preterm birth prevention
      without the use of maintenance oral tocolytic therapy.

PMID- 8885733
TI  - Nucleated red blood cells: an update on the marker for fetal asphyxia.
AB  - OBJECTIVE: Our goal was to update our experience with nucleated red blood cells
      as a marker for fetal asphyxia and to determine whether a relationship exists
      between the presence of nucleated red blood cells and long-term neurologic
      impairment. STUDY DESIGN: Nucleated red blood cell data from 153 singleton term
      neurologically impaired neonates were compared with cord blood nucleated red
      blood cells of 83 term nonasphyxiated newborns. Newborns with anemia,
      intrauterine growth restriction, and maternal diabetes were excluded. The group
      of neurologically impaired neonates was separated into the following subgroups:
      group I, persistent nonreactive fetal heart rate pattern from admission to
      delivery (n = 69); group II, reactive fetal heart rate on admission followed by
      tachycardia with decelerations and absent variability (n = 47); group III,
      reactive fetal heart rate on admission followed by an acute prolonged
      deceleration (n = 37). The first and highest nucleated red blood cell value and
      the time of nucleated red blood cell disappearance were assessed. RESULTS: The
      mean number of initial nucleated red blood cells was significantly higher in the
      group of neurologically impaired neonates (30.3 +/- 77.5, range 0 to 732 per 100
      white blood cells) than in the control group (3.4 +/- 3.0, range 0 to 12 per 100
      white blood cells) (p < 0.000001). When the group of neurologically impaired
      neonates was separated on the basis of timing of the neurologic impairment,
      distinct nucleated red blood cell patterns were observed. Significant differences
      were obtained between each of the three groups of neurologically impaired
      neonates and the normal group, with respect to initial nucleated red blood cells
      (group I, 48.6 +/- 106.9; group II, 11.4 +/- 9.8; group III, 12.6 +/- 13.4; p <
      or = 0.000002). Maximum nucleated red blood cell values were higher in group I
      (mean 51.5 +/- 108.9) than in groups II and III combined (mean 12.7 +/- 11.9) (p
      = 0.0005). Group I also had a longer clearance time (119 +/- 123 hours) than
      groups II and III combined (mean 59 +/- 64 hours) (p < 0.001). CONCLUSION: Our
      ongoing study indicates that nucleated red blood cells identify the presence of
      fetal asphyxia. When fetal asphyxia is present, distinct nucleated red blood cell
      patterns are observed that relate to the timing of fetal injury. In general,
      intrapartum injuries are associated with lower nucleated red blood cell values.
      Thus our data continue to support the concept that nucleated red blood cell
      levels may assist in determining the timing of fetal neurologic injury.

PMID- 8885734
TI  - Effect of chronic tocolytic therapy on maternal ventricular function in pregnant
      rabbits.
AB  - OBJECTIVE: Our purpose was to determine whether peripartum cardiomyopathy may be
      associated with chronic beta-mimetic tocolytic therapy. STUDY DESIGN: On
      gestational day 20 (term 31 days), two 200 microliter Alzet miniosmotic pumps
      were implanted in the subcutaneous tissue of pregnant New Zealand White rabbits.
      Each pump was filled with terbutaline (20 micrograms/microliter, n = 7) or saline
      solution (0.9%, n = 7) and infused continuously for 7 days. The rabbits were
      killed on the twenty-eighth gestational day. Maternal hearts were placed on a
      Langendorff (nonejecting) perfusion apparatus for assessment of cardiac function.
      At a constant perfusion pressure and heart rate left ventricular diastolic
      pressure was varied while left ventricular developed pressure and left
      ventricular +/- rate of pressure rise, index values of left ventricular
      contractility and relaxation, were continuously recorded. Comparisons between
      groups at each preload were made by analysis of variance. RESULTS: Hearts taken
      from terbutaline-treated rabbits exhibited periodic arrhythmias and mechanical
      alternans in five of seven hearts versus one of seven in the saline solution
      group. At a preload of 0 mm Hg both left ventricular developed pressure (88.0 vs
      48.4 mm Hg, p < 0.001) and left ventricular rate of pressure rise (1406 vs 653 mm
      Hg/sec, p < 0.001) were less in terbutaline-treated rabbits. At a preload of 10
      mm Hg left ventricular developed pressure (104.4 vs 56.7 mm Hg, p < 0.01) and
      rate of pressure rise (1424 vs 694 mm Hg/sec, p < 0.001) were also significantly
      less in terbutaline-treated rabbits. Left ventricular relaxation was also
      impaired at all preloads. CONCLUSIONS: In this model chronic administration of
      terbutaline during late pregnancy significantly depresses global maternal cardiac
      function.

PMID- 8885735
TI  - Rat uterine myometrium contains the gap junction protein connexin45, which has a
      differing temporal expression pattern from connexin43.
AB  - OBJECTIVE: Our purpose was to determine whether myometrial cell lines and rat
      myometrial tissue contained additional gap junction proteins besides connexin43.
      STUDY DESIGNS: Syrian hamster myocytes (SHM-ER) and human SK-UT-1 myometrial cell
      lines were analyzed for intercellular coupling by microinjection of Lucifer
      yellow. These cell lines and myometrial tissue isolated from pregnant rats were
      analyzed for connexin expression by ribonucleic acid blotting and
      immunofluorescence. RESULTS: SHM-ER and SK-UT-1 cells showed functional gap
      junctional coupling by intercellular passage of microinjected dye. Both cell
      lines contained connexin43 and connexin45 messenger ribonucleic acids but did not
      contain any other detectable connexin messenger ribonucleic acids.
      Immunofluorescence confirmed the presence of connexin43 and connexin45 proteins
      in these cells. Connexin 43 and connexin45 messenger ribonucleic acids and
      immunoreactive proteins were detected in pregnant rat myometrium. Connexin 43
      messenger ribonucleic acid levels increased dramatically at term. In contrast,
      connexin45 messenger ribonucleic acid was present in nonpregnant myometrium,
      remained relatively constant early in gestation, fell just before term, and more
      than doubled post partum. CONCLUSIONS: Rat uterine myometrium contains connexin45
      and connexin43. Coexpression of connexin45 with connexin43 in uterine myometrium
      may regulate gap junctional coupling between these cells. The different temporal
      expression patterns suggest that connexin45 and connexin43 may have different
      roles or that the ratio of these connexins may be important in the increased
      cellular coupling coincident with the onset of labor.

PMID- 8885736
TI  - Does the use of a tocolytic agent affect the success rate of external cephalic
      version?
AB  - OBJECTIVE: Our purpose was to study the effect of ritodrine tocolysis on the
      success rate of external cephalic version at > or = 36 weeks' gestation. STUDY
      DESIGN: This was a prospective, double-blinded, randomized study. All patients
      were > or = 36 weeks' gestation, confirmed by early ultrasonography. External
      cephalic version assessment included nonstress testing before and after external
      cephalic version and ultrasonographic evaluation of type of breech, estimated
      fetal weight, position of placenta and fetal spine, and amniotic fluid index.
      Patients were excluded if the breech was not mobile or if they had any
      contraindications to tocolysis or external cephalic version. After randomization
      283 patients received either ritodrine (111 micrograms/min) or identical placebo
      by intravenous infusion for > or = 20 minutes. Up to three attempts at external
      cephalic version under ultrasonographic surveillance were performed. With an
      alpha error of 0.05 and a beta of 0.2, 264 patients were required to complete
      this study. RESULTS: There were no differences between study groups in maternal
      age, body mass index, gestational age, amniotic fluid index, position of fetal
      spine, and placental location. Statistical analysis controlled for parity because
      parity had a major influence on success rates. There was a higher success rate in
      the group receiving ritodrine tocolysis (52% vs 42%, p = 0.028). Ritodrine
      improved success rates in nulliparous patients (43% vs 25%, p = 0.026) but not in
      parous subjects (66% vs 58%, p = 0.385). CONCLUSION: Ritodrine tocolysis improves
      the success rate of external cephalic version performed at > or = 36 weeks in
      nulliparous patients.

PMID- 8885737
TI  - The use of a surgical assist device to reduce glove perforations in postdelivery
      vaginal repair: a randomized controlled trial.
AB  - OBJECTIVE: Our purpose was to compare the effectiveness of a surgical assist
      device, SutureMate, to decrease glove perforations during postdelivery vaginal
      repair. STUDY DESIGN: This was a prospective randomized trial. After delivery
      surgeons who needed to perform vaginal repair were randomized to use the surgical
      assist device or to perform the repair in the usual fashion. After the repair,
      gloves were collected and the operator was asked to complete a standardized data
      form that was submitted with the gloves. The gloves were tested for perforations
      within 24 hours by the Food and Drug Administration-approved hydrosufflation
      technique. Comparisons were made with chi(2) statistics with p < 0.01 taken as
      being statistically significant with the use of a Bonferoni adjustment for
      multiple comparisons. RESULTS: A total of 476 glove sets were evaluated. The use
      of the surgical assist device significantly reduced the overall glove perforation
      rate from 28.3% in the control arm to 8.4% in the study arm (p = 0.0001). Rates
      of perforation varied with level of training and expertise but fell in all groups
      that used the device. Family physicians had the highest perforation rate in the
      control arm and benefited most from the device. A total of 76% of perforations
      were located in the thumb, index, and second fingers of the nondominant hand.
      Perforations were recognized in only 16% of the glove sets. The level of
      satisfaction with the device was mixed, but overall 50% of operators indicated
      that they were either satisfied or very satisfied with the device. CONCLUSION:
      The rate of glove perforation in postdelivery vaginal repair is high. The
      surgical assist device significantly reduced the rate of glove perforations.

PMID- 8885738
TI  - Positional effects on maternal cardiac output during labor with epidural
      analgesia.
AB  - OBJECTIVE: Our purpose was to test the hypothesis that the supine versus the
      lateral position is associated with a greater decrement in cardiac output after
      epidural analgesia in labor. STUDY DESIGN: Twenty-one normal term subjects were
      randomized to the left lateral or supine position in early labor. Cardiac output
      measured by the acetylene rebreathing method, stroke volume, heart rate, mean
      arterial pressure, and systemic vascular resistance were obtained at 5-minute
      intervals, beginning before a 500 ml intravenous fluid bolus (baseline) and
      ending 45 minutes after epidural injection. RESULTS: Mean baseline supine versus
      lateral group differences were significant for 21% lower cardiac output, 21%
      lower stroke volume, 19% higher mean arterial pressure, 50% higher systemic
      vascular resistance, and equivalent heart rate. In the supine group fluid bolus
      resulted in significantly increased cardiac output and stroke volume, decreased
      mean arterial pressure and systemic vascular resistance, and unchanged heart
      rate. In the supine group cardiac output and stroke volume decreased
      significantly after epidural injection. The lateral position group exhibited no
      hemodynamic alterations after fluid bolus or epidural. CONCLUSIONS: In contrast
      to the lateral position, the supine position is associated with a significant
      postepidural decrement in cardiac output, not identified by a change in heart
      rate. This likely reflects an inability to maintain stable preload volume in the
      supine position.

PMID- 8885739
TI  - The role of fetal karyotyping from unconventional sources.
AB  - OBJECTIVE: Our purpose was to determine whether fetal specimens, including
      pleural, ascitic, pericardial, facial, and cystic hygroma fluid or urine, are
      suitable sources for accurate chromosomal analysis. STUDY DESIGN: Thirty-nine
      samples of fetal fluid (pleural, n = 11; ascitic, n = 5; pericardial, n = 1; lung
      cyst, n = 1, facial cyst, n = 1; cystic hygroma, n = 7; and urine, n = 13) were
      cultured and analyzed with standard cytogenetic techniques for lymphocytes or
      amniotic fluid. These samples were obtained as part of the routine obstetric
      investigation and management. Conventional backup samples were also obtained.
      RESULTS: Karyotyping was successful in 34 of 39 samples. Cells were harvested
      from all pleural samples, three ascitic samples, and one hygroma fluid sample in
      2 to 4 days from 11 urine samples, one ascitic sample, and the remaining six
      hygroma samples in 7 to 11 days. Five cultures were unsuccessful. Samples with
      high lymphocyte counts yielded results as quickly as fetal blood. CONCLUSION: The
      use of "alternative" samples of fetal fluids for karyotyping may be considered
      when amniotic fluid or fetal blood is difficult to obtain. In selected cases this
      approach avoids the unnecessary risk of additional invasive procedures solely to
      obtain a karyotype.

PMID- 8885740
TI  - Selective reduction of multifetal pregnancies to twins improves outcome over
      nonreduced triplet gestations.
AB  - OBJECTIVE: Our purpose was to evaluate effects of multifetal pregnancy reduction
      on pregnancy complications and birth weights of remaining twin fetuses compared
      with expectantly managed triplets and nonreduced twins. STUDY DESIGN: Medical
      records of 54 triplet pregnancies, 59 twin pregnancies resulting from multifetal
      pregnancy reduction, and 88 sets of twins conceived with assisted reproductive
      techniques and delivered at New York Hospital after 24 weeks were retrospectively
      reviewed. Birth weights were corrected for gestational age at delivery by use of
      a formula derived from composite standardized growth curves. Statistical analysis
      was performed with chi(2) analysis and Student t test. RESULTS: Twins remaining
      after reduction and nonreduced twins were less likely to have preeclampsia than
      were triplets (14% and 23% vs 30%) and to be delivered before 36 weeks (39% and
      27% vs 72%). They had birth weights that were > 100 gm larger than those of
      triplets even when corrected for gestational age. Reduced twins were similar to
      nonreduced twins in all parameters studied. CONCLUSIONS: Multifetal pregnancy
      reduction results in pregnancy complications, gestational age, and birth weights
      closer to those of nonreduced twins than to expectantly managed triplets.

PMID- 8885741
TI  - Analysis of repeat cesarean delivery indications: implications of heterogeneity.
AB  - OBJECTIVE: Our purpose was to describe the relative contributions and
      characteristics of various subgroups of patients to the overall repeat cesarean
      delivery rate and to determine modifiable practice patterns that might lead to
      fewer repeat cesarean deliveries. STUDY DESIGN: Hospital records of all women
      with a previous cesarean section who were delivered between Jan. 1 and June 30,
      1994, at St. Peter's Medical Center in New Brunswick, New Jersey, were reviewed.
      Four groups were identified: (1) elective repeat cesarean, (2) "indicated" repeat
      cesarean, (3) failed vaginal birth after cesarean, and (4) successful vaginal
      birth after cesarean. Descriptive and outcome data were collected. RESULTS: There
      were 406 patients, 376 of whom had complete records available for review. Of
      these, 235 had a repeat cesarean delivery because of the following reasons:
      elective (107, 45%), "indicated" (56, 24%), and failed vaginal birth after
      cesarean (72, 31%). The remaining 141 patients had a vaginal birth after
      cesarean. Patients with private or health maintenance organization insurance were
      nearly seven times more likely to have a repeat cesarean delivery as an elective
      procedure as compared with Medicaid or self-pay patients (odds ratio 6.88, 95%
      confidence interval 2.33 to 20.38). The failed vaginal birth after cesarean group
      was characterized by more frequent inductions of labor, less use of amniotomy,
      and very early epidural placement. CONCLUSIONS: Examination of patient
      characteristics is required to identify population-specific strategies to reduce
      repeat cesarean delivery rates. Modifiable practice patterns exist that may lead
      to interventions to reduce repeat cesarean delivery rates.

PMID- 8885742
TI  - Complications of midtrimester pregnancy termination: the effect of prior cesarean
      delivery.
AB  - OBJECTIVE: Our purpose was to determine whether a prior cesarean delivery affects
      the incidence of complications in women having an indicated midtrimester medical
      pregnancy termination. STUDY DESIGN: A retrospective review of women who
      underwent a midtrimester medical termination of pregnancy from January 1980 to
      July 1995 ascertained obstetric history, uterotonic agent(s), and the occurrence
      of uterine rupture, blood transfusion, or curettage. The frequencies of maternal
      complications were compared in women with and without a prior cesarean section.
      RESULTS: Our study population included 606 women with a mean gestational age of
      21.1 +/- 3.1 weeks and a mean maternal age of 26.3 +/- 7 years. Seventy-nine
      (13%) had undergone a prior cesarean section. There was no significant difference
      in the need for curettage between women with and without a prior cesarean
      section. However, there was an increased need for blood transfusions in women
      with a prior cesarean delivery (11.4% vs 5.3%, odds ratio 2.3, 95% confidence
      interval 1.1 to 5.0, p = 0.04). The incidence of uterine rupture was
      significantly higher among women with a prior cesarean (3.8% vs 0.2%, odds ratio
      20.8, 95% confidence interval 14.1 to 104, p = 0.008). CONCLUSION: Our data
      suggest that a prior cesarean section is a risk factor for uterine rupture and
      blood transfusion in women having a midtrimester pregnancy termination.

PMID- 8885743
TI  - Postoperative incision complications after cesarean section in patients with
      antepartum syndrome of hemolysis, elevated liver enzymes, and low platelets
      (HELLP): does delayed primary closure make a difference?
AB  - OBJECTIVE: Our purpose was to evaluate wound complications between patients with
      antepartum HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome with
      primary closure versus delayed closure and Pfannenstiel versus midline skin
      incisions. STUDY DESIGN: Medical records of patients with antepartum HELLP
      syndrome undergoing cesarean section were examined for type and timing of skin
      closure: Pfannenstiel versus midline skin incision and primary versus delayed
      closure. The immediate (before hospital discharge) and late (2-week postoperative
      check) wound complications were analyzed with respect to timing of wound closure
      and type of skin incision. RESULTS: A total of 104 patients were identified; 75
      had a primary skin closure and 29 had a delayed closure 48 to 72 hours
      postoperatively. Immediate wound complications (wound infection, hematoma),
      occurred in 18 (26%) patients who had primary closure versus 8 (24%) who had a
      delayed closure, odds ratio 1.13 (95% confidence interval 0.39 to 3.27). A late
      wound breakdown was seen in only 1 patient with primary closure but in none with
      delayed closure. There were no fascial wound dehiscences. No statistical
      difference in wound complication was found between midline (primary, delayed) and
      Pfannenstiel (primary, delayed) incisions, odds ratio 0.65 (95% confidence
      interval 0.23 to 1.88). CONCLUSION: In women with antepartum HELLP syndrome
      delivered by cesarean section the frequency of wound complications is not
      influenced by type of skin incision or time of skin closure (primary or delayed).

PMID- 8885744
TI  - Is there a benefit to episiotomy at spontaneous vaginal delivery? A natural
      experiment.
AB  - OBJECTIVE: Our purpose was to examine the association between maternal vaginal
      and perineal morbidity and episiotomy performed at spontaneous vaginal delivery.
      STUDY DESIGN: We obtained data from 17,483 consecutive spontaneous vaginal
      deliveries and compared the yearly rates of episiotomy, lacerations, and
      potential confounders with linear regression and stratified analyses. RESULTS:
      Between 1976 and 1994 the use of episiotomy fell significantly (86.8% to 10.4%,
      R2 = 0.92, p = 0.0001). This change was associated with a fall in the rate of
      third- and fourth-degree lacerations (9.0% to 4.2%, R2 = 0.59, p = 0.0001) and a
      rise in the rate of intact perinea (10.3% to 26.5%, R2 = 0.68, p = 0.0001) and
      vaginal lacerations (5.4% to 19.3%, R2 = 0.77, p = 0.0001). These associations
      held in separate analyses stratified by parity and birth weight, except for the
      subgroup of nulliparous women with macrosomic infants. CONCLUSION: At our
      institution a large reduction in the use of episiotomy in spontaneous vaginal
      deliveries was associated with a significant reduction in perineal trauma in all
      groups of women except for nulliparous women with macrosomic infants.

PMID- 8885745
TI  - The factor V Leiden mutation may predispose women to severe preeclampsia.
AB  - OBJECTIVE: A recent study showed that resistance to activated protein C may
      underlie some cases of severe preeclampsia. A common missense mutation in the
      factor V gene, the Leiden mutation, is the most frequent genetic cause of
      resistance to activated protein C. Our objective was to determine whether this
      mutation is more prevalent in patients with severe preeclampsia than in
      normotensive controls. STUDY DESIGN: Deoxyribonucleic acid was extracted from
      whole blood of 158 gravid women meeting criteria of The American College of
      Obstetricians and Gynecologists for severe preeclampsia and 403 normotensive
      gravid women. The polymerase chain reaction was used to amplify exon 10 of the
      factor V gene, followed by allele-specific restriction with Mnl 1 for mutation
      detection. Results were analyzed with a chi(2) contingency table. RESULTS: No
      patients were homozygous for the Leiden mutation. Fourteen of 158 women with
      severe preeclampsia (8.9%) were heterozygous for the Leiden mutation compared
      with 17 of 403 normotensive gravid controls (4.2%). The difference in frequency
      between women with severe preeclampsia and normotensive controls was
      statistically significant, chi(2) 4.686, p = 0.03. CONCLUSIONS: Our data suggest
      that carriers of the factor V Leiden mutation are at increased risk for severe
      preeclampsia. Deoxyribonucleic acid analysis for the factor V Leiden mutation
      could serve as one component of a genetic screening profile for preeclampsia and
      other adverse pregnancy outcomes. Women who carry this mutation are at increased
      risk for deep venous thrombosis. Carriers of this common thrombophilic mutation
      may be identified so that adequate counseling regarding future contraceptive
      usage and effective thromboembolic prophylaxis during pregnancy and surgical
      procedures may be offered.

PMID- 8885746
TI  - Detection of adrenomedullin, a hypotensive peptide, in amniotic fluid and fetal
      membranes.
AB  - OBJECTIVE: Our purpose was to determine whether adrenomedullin, a multifunctional
      regulatory peptide involved in blood flow regulation and growth stimulation and
      with antimicrobial activity, was a component of amniotic fluid from second
      trimester human fetus and to determine the source of this peptide. STUDY DESIGN:
      A prospective descriptive study was performed on 134 patients undergoing
      amniocentesis after genetic counseling, ultrasonography, and informed consent.
      Adrenomedullin expression was determined by immunocytochemical analysis, Western
      blot analysis, reverse transcriptase-polymerase chain reaction, and in situ
      reverse transcriptase-polymerase chain reaction in fetal membranes and with
      radioimmunoassay in amniotic fluids. RESULTS: Radioimmunoassay of the 134
      amniotic fluid specimens revealed adrenomedullin-like immunoreactivity in all of
      them, ranging in concentration from 10 to 300 fmol/25 microliters (170 +/- 62
      fmol/25 microliters). Immunocytochemical analysis, Western blot analysis, reverse
      transcriptase-polymerase chain reaction, and in situ reverse transcriptase
      polymerase chain reaction further established the expression of adrenomedullin
      protein and messenger ribonucleic acid in fetal amniotic membranes, suggesting
      that this organ is the source of amniotic adrenomedullin. CONCLUSIONS: Our
      results clearly demonstrate the presence of adrenomedullin in second-trimester
      human amniotic fluid and adrenomedullin messenger ribonucleic acid and protein in
      amniotic membranes, suggesting that adrenomedullin is a hormone involved in the
      maintenance of normal pregnancy. Further studies with these molecular tools are
      in progress to determine the precise role of this hormone and whether
      adrenomedullin plays a role in the pathogenesis of various disorders of
      pregnancy.

PMID- 8885747
TI  - Circulating maternal corticotropin-releasing hormone and gonadotropin-releasing
      hormone in normal and abnormal pregnancies.
AB  - OBJECTIVE: Corticotropin-releasing hormone and gonadotropin-releasing hormone are
      produced by the human placenta and have been measured in the maternal circulation
      during pregnancy. Our objective was to determine concentrations of these
      substances in maternal plasma throughout normal pregnancies and in early
      pregnancy loss. STUDY DESIGN: Fifty-one pregnant women were followed up
      prospectively and plasma samples were drawn at 8, 10, 12, 14, 16, 28, and 36
      weeks' gestation and during labor. Specific and sensitive radioimmunoassays were
      used to determine corticotropin-releasing hormone and gonadotropin-releasing
      hormone concentrations in these samples. RESULTS: Blood samples were drawn at all
      time points and outcome data were available from 33 women who completed their
      pregnancies at term without complications. In this normal group circulating
      corticotropin-releasing hormone concentrations increased from low or undetectable
      concentrations at 8 weeks (< or = 23.2 +/- 1.3 pg/ml, mean +/- SEM) to measurable
      values at 16 weeks (34.3 +/- 2.2 pg/ml). Thereafter there was a significant
      increase to 1294 +/- 113 pg/ml in labor. Gonadotropin-releasing hormone
      demonstrated a trimodal distribution, increasing significantly from 8 to 14
      weeks, decreasing at 16 weeks, and increasing again by term. The ratio of
      corticotropin-releasing hormone to gonadotropin-releasing hormone in the normal
      group demonstrated a 30-fold increase from 8 weeks to term. In eight cases of
      early pregnancy loss corticotropin-releasing hormone and gonadotropin-releasing
      hormone concentrations were not significantly different from those of the normal
      group in early pregnancy. In two cases of premature delivery gonadotropin
      releasing hormone concentrations and ratios were within the normal range;
      corticotropin-releasing hormone levels were normal in both cases of premature
      delivery. CONCLUSION: In this study we determined maternal concentrations of
      corticotropin-releasing hormone and gonadotropin-releasing hormone in normal
      pregnancies and in labor at term. Neither maternal concentrations of
      corticotropin-releasing hormone nor gonadotropin-releasing hormone were useful in
      identifying pregnant women at risk for early pregnancy loss.

PMID- 8885748
TI  - Metabolic response to meal eating and extended overnight fast in twin gestation.
AB  - OBJECTIVE: Our purpose was to compare the metabolic response to normal meal
      eating and the vulnerability to starvation ketosis in twin versus singleton
      gestation. STUDY DESIGN: Data are reported on 10 twin and 10 singleton
      nondiabetic gestations enrolled in a 40-hour metabolic study. Singletons were age
      (+/- 5 years) and prepregnancy weight (+/- 10% ideal body weight) matched with
      twins. The diet (35 kcal/kg ideal body weight for singletons, 40 kcal/kg ideal
      body weight for twins) was distributed as one fifth at 8 AM, two fifths at 1 PM,
      and two fifths at 6 PM. An overnight fast was extended until noon the following
      day. Glucose and beta-hydroxybutyrate measurements were made hourly except at
      night, when they were made every 2 hours. Insulin values were obtained before and
      after dinner and on the day when breakfast was delayed. RESULTS: The glucose,
      beta-hydroxybutyrate, and insulin excursions in response to meal eating from 8 AM
      to 12:00 noon on day 1 were similar in twin and singleton pregnancies (analysis
      of variance for repeated measures, p < 0.05). On day 2, when breakfast was
      delayed, a progressive decrement in glucose was observed in both twins and
      singletons (p = 0.4682). Concurrently, there was a progressive rise in beta
      hydroxybutyrate in both twins and singletons, which was significantly greater for
      twins compared with singletons (p = 0.002). CONCLUSIONS: These data indicate that
      twin gestations are more vulnerable to the accelerated starvation of late normal
      pregnancy than singletons are in spite of additional caloric intake. We speculate
      that the observed difference may be the result of the increased metabolic demands
      of twin gestation.

PMID- 8885749
TI  - M-mode echocardiographic evaluation of fetal and infant hearts: longitudinal
      follow-up study from intrauterine life to year one.
AB  - OBJECTIVE: Our purpose was to evaluate cardiac variables, including right and
      left end-diastolic and end-systolic dimensions by use of M-mode echocardiography
      during fetal, neonatal (transitional), and infancy periods to understand
      hemodynamic adaptation during these periods. STUDY DESIGN: Fifty-three fetuses
      were enrolled in this study. Echocardiography evaluations were started as early
      as the sixteenth week of gestation and were repeated every 4 to 6 weeks until
      term, on postnatal days 1 and 2, and at 6 weeks, 6 months, and 12 months of age.
      End-diastolic and end-systolic measurements were made according to published
      standards. Mean and SEM for each of the end-diastolic and end-systolic
      measurements were calculated for each of 11 study periods. Data were analyzed by
      one-way analysis of variance, corrected for repeated measures, and in the case of
      right and left ventricular differences paired t tests were used for significance.
      RESULTS: Left ventricular end-diastolic and end-systolic correlated positively
      with advancing age (R2 = 0.93, p < 0.0001), right ventricular end-diastolic also
      correlated with advancing age (R2 = = 0.361, p < 0.05), and right ventricular end
      diastolic was significantly larger than left ventricular end-diastolic in utero
      (p < 0.01), whereas the opposite was true after birth (p < 0.0001). Heart rate
      significantly decreased with advancing age (p < 0.001), whereas ejection fraction
      for either the right or the left ventricle did not change significantly with
      advancing age. CONCLUSION: This suggests that under basal conditions the
      ventricles can meet the increased demands in cardiac output by increasing
      ventricular dimensions without having to increase contractility reserve.

PMID- 8885750
TI  - Fetal cerebral, circulatory, and metabolic responses during heart rate
      decelerations with umbilical cord compression.
AB  - OBJECTIVE: The purpose of this study was to determine the cerebral, circulatory,
      and metabolic responses of the ovine fetus near term to umbilical cord
      compression with variable-type fetal heart rate decelerations. STUDY DESIGN: Nine
      fetal sheep, at 0.9 of gestation, were studied before, during, and after
      umbilical cord occlusion for 1-minute and again after repetitive 1-minute cord
      occlusions every 5 minutes for 1 hour, with resultant fetal heart rate
      decelerations of approximately 90 beats/min. Brachiocephalic arterial and
      sagittal venous blood was analyzed for oxygen content, blood gases and pH,
      glucose, and lactate. Cerebral and upper body blood flow was measured with the
      microsphere technique. RESULTS: Umbilical cord occlusion with moderate to severe
      variable-type fetal heart rate deceleration resulted in an immediate drop in
      arterial PO2 by approximately 7 torr, an increase in PCO2 by approximately 9
      torr, and a small but significant increase in lactate levels. Cerebral oxidative
      metabolism was well maintained but required an increase in fractional oxygen
      extraction because the variable change in cerebral blood flow was insufficient to
      maintain oxygen delivery. A redistribution of upper body blood flow was evident,
      with that to the bran and heart variably maintained or increased whereas that to
      muscle tissue was markedly decreased. Repetitive umbilical cord occlusion over 1
      hour resulted in a significant drop in fetal arterial pH, with the acidemia mixed
      as PCO2 increased approximately 6 torr, whereas lactate levels increased almost
      fourfold. CONCLUSION: Although cerebral oxidative metabolism appears to be well
      maintained during moderate to severe variable-type fetal heart rate decelerations
      with umbilical cord occlusion, the need to increase fractional oxygen extraction
      and the redistribution of blood flow from carcass tissues may contribute to an
      accumulation of lactic acid both within the brain and systemically when such an
      insult occurs repeatedly.

PMID- 8885751
TI  - Mathematic modeling of human amniotic fluid dynamics.
AB  - OBJECTIVE: We sought to develop a model quantifying the relative contributions of
      fetal swallowing and intramembranous flow to amniotic fluid dynamics during human
      gestation. We then used the model to simulate the impact of absent swallowing on
      amniotic fluid volume. STUDY DESIGN: The model was developed with published data
      for normal human amniotic fluid volume and composition, human fetal urine flow
      rate and composition (11 to 42 weeks), and extrapolated data from ovine lung
      fluid production. Fetal swallowing and intramembranous flow were calculated with
      assumptions that (1) swallowed fluid is isotonic to amniotic fluid, (2)
      intramembranous flow is free water diffusion, and (3) 50% of lung fluid is
      swallowed. The model was then applied to simulate absent fetal swallowing and
      variable (0%, 50%) proportions of swallowed lung fluid were used as a
      representation of esophageal atresia-tracheal fistula variations. RESULTS: Fetal
      swallowed volume and intramembranous flow linearly increase until 28 to 30 weeks.
      Daily swallowed volume then exponentially increases to a maximum of 1006 ml/day
      at term, whereas intramembranous flow continues on a linear trend to reach 393
      ml/day at term. With absent swallowing and variable amounts of lung fluid
      swallowed (0%, 50%), predicted amniotic fluid volume is similar to normal values
      through 20 weeks, exceeds the 95% confidence interval for normal amniotic fluid
      volume at 29 to 30 weeks' gestation (approximately 2000 ml), and then
      exponentially increases. Predicted amniotic fluid osmolality (280 to 257 mOsm/kg)
      is slightly lower than actual values although within the clinically normal range.
      CONCLUSIONS: This model indicates that the normal reduction in amniotic fluid
      volume beginning at 34 weeks results from the marked increase in swallowed volume
      during the third trimester. Additionally, this model correlates well with the
      timing of the initial clinical presentation of polyhydramnios observed in some
      fetuses with conditions that result in absent or reduced swallowing or
      gastrointestinal atresia. Modeling of amniotic fluid dynamics can predict normal
      changes in fetal fluid exchange and may aid in understanding of amniotic fluid
      imbalances.

PMID- 8885752
TI  - A prospective randomized trial of two solutions for intrapartum amnioinfusion:
      effects on fetal electrolytes, osmolality, and acid-base status.
AB  - OBJECTIVE: Our purpose was to compare the effects of intrapartum amnioinfusion
      with normal saline solution versus lactated Ringer's solution plus physiologic
      glucose on neonatal electrolytes and acid-base balance. STUDY DESIGN: Patients
      undergoing amnioinfusion for obstetric indications were randomized to receive
      normal saline solution or lactated Ringer's solution plus physiologic glucose at
      standardized amnioinfusion rates. Data were collected prospectively on maternal
      demographics, course of labor, and maternal and neonatal outcome. Arterial cord
      blood was obtained for analysis of electrolytes, glucose, osmolality, lactic
      acid, and blood gases. Control subjects with normal fetal heart rate patterns,
      and clear amniotic fluid not receiving amnioinfusion were studied concurrently.
      RESULTS: Data were collected on 59 patients (21 normal saline solution, 18
      lactated Ringer's solution plus physiologic glucose, and 20 controls). Maternal
      demographics, course of labor, and neonatal outcome were similar in all three
      groups. Cesarean sections were performed more often in the amnioinfusion groups
      (33.3% for normal saline solution, 38.9% for lactated Ringer's solution plus
      physiologic glucose) than in the control group (5.0%), p < 0.05. Cord arterial
      electrolytes, glucose, osmolality, lactic acid, and blood gases were not altered
      by amnioinfusion with either solution. CONCLUSION: Intrapartum amnioinfusion with
      normal saline solution or lactated Ringer's solution plus physiologic glucose has
      no effect on neonatal electrolytes or acid-base balance.

PMID- 8885753
TI  - Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy:
      review of 11 cases.
AB  - OBJECTIVE: Little information exists regarding thrombotic thrombocytopenic
      purpura and hemolytic uremic syndrome during pregnancy. We report a series of
      thrombotic thrombocytopenic purpura and hemolytic uremic syndrome complicating
      pregnancy, with emphasis on diagnosis and management of this rare disorder. STUDY
      DESIGN: Between January 1988 and February 1996, 11 women with either thrombotic
      thrombocytopenic purpura (n = 8) or hemolytic uremic syndrome (n = 3) were
      evaluated. Clinical and laboratory findings and maternal and neonatal outcomes
      were recorded from the medical records. RESULTS: Eight of the 11 women were in
      the third trimester or peripartum period, and three were seen before fetal
      viability. Treatment included fresh-frozen plasma in all women, plasmapheresis (n
      = 8), packed red blood cells (n = 9), and platelet transfusions (n = 5); 1
      patient required splenectomy. There were two maternal deaths. Of the 9 surviving
      women, 4 had chronic renal disease, 1 of whom also had residual neurologic
      deficit. Preterm delivery occurred in 5 of 8 pregnancies continuing beyond 20
      weeks. Indications for delivery in these 5 women included worsening maternal
      medical disease, nonreassuring fetal testing, and spontaneous preterm labor. Six
      of 8 women with viable fetuses underwent cesarean delivery. These 6 infants were
      born in good condition without thrombocytopenia. Of the remaining 2 infants
      delivered vaginally, one was healthy at 35 weeks and the other was stillborn.
      CONCLUSION: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome
      complicating pregnancy is associated with high maternal mortality and long-term
      morbidity. Preterm delivery and intrauterine fetal death are frequent
      complications of these pregnancies. Improved survival after this disorder has
      been attributed to aggressive treatment with plasma transfusion or
      plasmapheresis.

PMID- 8885754
TI  - Intrahepatic cholestasis of pregnancy: perinatal outcome associated with
      expectant management.
AB  - OBJECTIVE: Our goal was to compare the pregnancy outcomes of patients with
      intrahepatic cholestasis of pregnancy managed expectantly with antepartum testing
      with those of other patients who were followed up with a similar testing scheme.
      STUDY DESIGN: Cases of intrahepatic cholestasis of pregnancy monitored with
      antepartum testing at our institution over a 7-year period were reviewed. Their
      pregnancy outcomes were compared with those of control patients followed up with
      the same testing scheme for a history of stillbirth. Both groups had at least
      weekly nonstress tests and amniotic fluid assessment until spontaneous labor or
      delivery for standard obstetric indications RESULTS: Seventy-nine patients were
      analyzed in each group. The two groups did not differ with respect to the mean
      gestational age at delivery (38.5 vs 38.8 weeks), birth weight (3216 vs 3277 gm)
      or incidence of preterm delivery (14% vs 7.6%). Abnormal antepartum testing
      prompting delivery was more common in the control group (25% vs 7.6%, p < 0.05).
      The risk of meconium passage was higher in the cholestasis group (44.3% vs 7.6%,
      p < 0.05). Two antepartum fetal deaths occurred in the cholestasis group at 36 to
      37 weeks' gestation within 5 days of normal results of antepartum testing. Thick
      meconium and appropriate birth weight were noted in both infants. No gross
      anomalies were found in either infant. CONCLUSION: Intrahepatic cholestasis of
      pregnancy is associated with adverse perinatal outcome not predicted by
      conventional fetal surveillance.

PMID- 8885755
TI  - Lowering the threshold for the diagnosis of gestational diabetes.
AB  - OBJECTIVE: Our purpose was to determine whether lowering the diagnostic threshold
      for gestational diabetes mellitus on 3-hour 100 gm oral glucose tolerance testing
      will select a population at risk for adverse perinatal outcome. STUDY DESIGN: In
      this retrospective study 434 patients with an abnormal 50 gm glucose screen
      result (> or = 140 mg/dl) underwent a standardized 3-hour oral glucose tolerance
      test. The results were stratified according to maternal weight and the criteria
      recommended by Sacks or Carpenter. Birth weight and rate of macrosomia were the
      primary perinatal outcome variables analyzed. RESULTS: Analysis of the data set
      stratified according to the Sacks criteria revealed results very similar to the
      Carpenter criteria data set. Patients who would have been newly diagnosed with
      gestational diabetes mellitus only if the lowered criteria were used (group 2)
      were older and heavier. No other variable comparisons achieved statistical
      significance. When the same patients were stratified according to prepregnancy
      weight, overweight patients were older, gained less weight during the third
      trimester, underwent cesarean section more often, and had higher cumulative
      maternal morbidity. Regression analysis showed that the degree of hyperglycemia
      did not predict macrosomia or influence birth weight, but prepregnant maternal
      body mass index was associated with macrosomia. CONCLUSIONS: Fetal macrosomia is
      influenced by maternal prepregnant body mass index. Lowering the glucose
      tolerance test threshold would result in overdiagnosis of gestational diabetes
      mellitus without improving perinatal outcome.

PMID- 8885756
TI  - Maternal serum interleukin-6 concentrations in patients with preterm premature
      rupture of membranes and evidence of infection.
AB  - OBJECTIVE: Our purpose was to determine whether maternal serum interleukin-6
      concentrations are elevated in patients with preterm premature rupture of
      membranes and intrauterine infection. STUDY DESIGN: By use of a sensitive enzyme
      linked immunosorbent assay maternal serum interleukin-6 concentrations were
      measured in 110 samples from patients at 22 to 34 weeks gestation with the
      following conditions: nonlaboring, uninfected controls (n = 46), preterm
      premature rupture of membranes > 48 hours before delivery without infection (n =
      27), preterm premature rupture of membranes 24 to 48 hours before delivery with
      subsequent clinical or histologic infection (n = 11), and preterm premature
      rupture of membranes < 24 hours before delivery with infection present by
      clinical or histologic criteria (n = 26). The Mann-Whitney U test was used for
      statistical analysis. RESULTS: Compared with that of nonlaboring controls, serum
      interleukin-6 was significantly higher in patients with preterm premature rupture
      of membranes < 24 hours before delivery with evidence of infection (17.2 vs 1.6
      pg/ml, p < 0.0001). Patients with preterm premature rupture of membranes 24 to 48
      hours before delivery who had infection had significantly higher interleukin-6
      concentrations than did nonlaboring controls (3.6 vs 1.6 pg/ml, p = 0.006). There
      was no significant difference in interleukin-6 concentrations in nonlaboring
      controls compared with patients with preterm premature rupture of membranes when
      serum was obtained > 48 hours before delivery (1.6 vs 1.6 pg/ml, p = 0.90). A
      serum interleukin-6 level > or = 8 pg/ml yielded a sensitivity of 81%, a
      specificity of 99%, a positive predictive value of 96%, and a negative predictive
      value of 95% for identifying intrauterine infection in patients with preterm
      premature rupture of membranes on the day of delivery. CONCLUSIONS: Maternal
      serum interleukin-6 concentrations are elevated in patients with preterm
      premature rupture of membranes with clinical or histologic chorioamnionitis.

PMID- 8885757
TI  - Induction and posttranslational expression of cytokines in a first-trimester
      trophoblast cell line by lipopolysaccharide.
AB  - OBJECTIVES: The response to infection by human first-trimester trophoblasts is a
      poorly understood event. This study was undertaken to determine whether first
      trimester trophoblasts are capable of responding to an infection stimulus and
      mediating an immune response. STUDY DESIGN: HTR-8/SVneo cells were exposed to
      lipopolysaccharide (1 microgram/ml) or media alone for either 0, 2, 4, 6, 8, or
      24 hours. Northern analysis was conducted by use of a panel of antisense cytokine
      probes. Enzyme-linked immunosorbent assays specific for either interleukin-1
      alpha, interleukin-6, interleukin-8, or transforming growth factor-beta 1 were
      conducted on corresponding cell culture supernatants, and the kinetics of
      expression were determined. RESULTS: Interleukin-1 alpha, interleukin-6,
      interleukin-8, and transforming growth factor-beta 1 transcription occurred
      maximally between 2 and 8 hours of culture in media containing
      lipopolysaccharide, with a subsequent diminution of response. Enzyme-linked
      immunosorbent assay analysis corroborated lipopolysaccharide induction seen at
      the level of transcription, with significant posttranslational expression of
      these cytokines being detected between 2 and 24 hours in culture (p < 0.01).
      CONCLUSIONS: Expression of the proinflammatory cytokines interleukin-1 alpha,
      interleukin-6, interleukin-8 and transforming growth factor-beta 1 strongly
      support the contention that human first-trimester trophoblasts are capable of
      responding to an infection stimulus and eliciting an immune response through
      cytokine-based immune signaling.

PMID- 8885758
TI  - Ampicillin for neonatal group B streptococcal prophylaxis: how rapidly can
      bactericidal concentrations be achieved?
AB  - OBJECTIVE: Our purpose was to determine how rapidly bactericidal concentrations
      of ampicillin against group B streptococci are achieved in amniotic fluid and
      cord blood after a 2 gm maternal infusion. STUDY DESIGN: Ampicillin was
      administered at varying time intervals between 3 and 67 minutes before elective
      cesarean delivery in 40 women. Samples of amniotic fluid were obtained by
      amniocentesis just before the uterine incision was made. Umbilical and maternal
      blood were obtained at the time of delivery. Ampicillin concentrations were
      measured by high-pressure liquid chromatography. RESULTS: The mean concentrations
      of ampicillin measured in maternal and umbilical cord sera all exceeded the
      minimum bactericidal concentrations reported for group B streptococci (0.25 to
      2.0 micrograms/ml) and were achieved as soon as 5 minutes after ampicillin
      infusion. Similarly, bactericidal levels of ampicillin in the amniotic fluid
      could be detected as early as 5 minutes. However, such concentrations of
      ampicillin in the amniotic fluid were achieved in only 85% of the pregnancies
      studied. CONCLUSIONS: Bactericidal levels of ampicillin against group B
      streptococci can usually be achieved rapidly in both fetal blood and amniotic
      fluid after a standard 2 gm intravenous dose given to the mother for neonatal
      prophylaxis.

PMID- 8885759
TI  - Automobile crash simulation with the first pregnant crash test dummy.
AB  - OBJECTIVE: Our goal was to develop a pregnancy insert for the Hybrid III (First
      Technology, Farmington, Mich.) crash dummy allowing evaluation of the effects of
      various restraint conditions on energy transmission to both the fetal and
      maternal compartments. STUDY DESIGN: A pregnancy insert with an elasticized vinyl
      uterine shell, simulated silicon amniotic fluid, and a 28-week simulated fetus
      was fitted to a female crash dummy. The fetus was instrumented with
      accelerometers in the head and thorax and a transducer to measure force
      transmission through the uterus. Thirty-nine crash tests were run under six
      different restraint conditions at speeds ranging from 10 to 25 miles/hr. Fetal
      responses were compared for different restraint conditions. RESULTS: Increasing
      speed of the crash resulted in greater force transmission through the uterus.
      Placement of the lap belt over the uterus instead of under the uterus resulted in
      a threefold to fourfold increase in force transmission through the uterus at all
      speeds tested. Air bag deployment in the unbelted or out-of-position dummy
      (laying against air bag) appears to impart significant energy transmission to the
      fetus. CONCLUSIONS: Energy transmission can be measured in terms of both
      abdominal force and acceleration within the fetal head and thorax. This new dummy
      demonstrates substantial transmission of energy, which is accentuated in some
      restraint conditions commonly used by pregnant women. The use of the 3-point
      restraint system appears to reduce the likelihood of injury in this model.

PMID- 8885760
TI  - Clinical significance of prenatal ultrasonographic intestinal dilatation in
      fetuses with gastroschisis.
AB  - OBJECTIVE: Our purpose was to evaluate the clinical significance of intestinal
      dilatation detected by prenatal ultrasonographic examination in fetuses with
      gastroschisis. STUDY DESIGN: A retrospective chart review was performed of all
      patients cared for at Los Angeles County/University of Southern California
      Women's and Children's Hospital with the prenatal diagnosis of gastroschisis over
      a 7-year period (1988 through 1995). Patients were divided into two groups on the
      basis of the presence or absence of ultrasonographically measured fetal bowel
      diameter of > or = 17 mm. Neonatal outcomes of the two groups were compared.
      RESULTS: Twenty-one patients met the entry criteria during the study period.
      Fetuses with maximal bowel diameter of > or = 17 mm did not have a longer time to
      full oral feeding, a longer initial hospital stay, or a greater need for bowel
      resection when compared with fetuses with a bowel diameter < 17 mm. Two newborns
      underwent bowel resection because of intestinal atresia. Prenatal
      ultrasonographic examination failed to show significant bowel dilatation in
      either infant. CONCLUSION: Our data suggest that prenatal evidence of intestinal
      dilatation in fetuses with gastroschisis does not predict immediate neonatal
      outcome. Thus this finding is not an appropriate indication for preterm delivery
      in the absence of other evidence of fetal compromise.

PMID- 8885761
TI  - Prevention of maternal hypotension by epidural administration of ephedrine
      sulfate during lumbar epidural anesthesia for cesarean section.
AB  - OBJECTIVE: Our purpose was to determine whether epidural administration of
      ephedrine sulfate simultaneously with induction of lumbar epidural anesthesia for
      nonemergency cesarean section reduces the incidence of maternal hypotension.
      STUDY DESIGN: In a double-blinded, placebo-controlled trial, 50 normotensive,
      nonlaboring, American Society of Anesthesiologists' class I or II women with
      term, uncomplicated, singleton pregnancies were randomly assigned to have normal
      saline solution or ephedrine sulfate administered epidurally and coincidentally
      with induction of lumbar epidural anesthesia for nonemergency cesarean section.
      All subjects were prehydrated with 25 ml/kg crystalloid and placed in supine
      position on a 15-degree, right-sided wedge before and after induction. Serial
      blood pressures were compared with baseline blood pressures, chosen as the
      average of three preinduction blood pressures. Hypotension was defined as a
      decline in systolic blood pressure to < or = 90 mm Hg or < or = 70% of baseline.
      Differences between groups were analyzed by Fisher's Exact Test. Significance was
      determined at p < 0.05. RESULTS: The incidence of hypotension in the control
      group was 24%, which was not significantly different from the incidence of 32% in
      the treated group. CONCLUSION: Prophylactic epidural administration of ephedrine
      sulfate does not reduce the incidence of maternal hypotension after lumbar
      epidural anesthesia for nonemergency cesarean section.

PMID- 8885762
TI  - Does station of the fetal head at epidural placement affect the position of the
      fetal vertex at delivery?
AB  - OBJECTIVE: The objective study was to determine whether epidural placement before
      engagement of the fetal head is associated with an increase in the incidence of
      malposition at delivery. STUDY DESIGN: We performed a retrospective cohort study
      to ascertain the relation between station at epidural placement and malposition.
      Three hundred fifty-seven patient records were reviewed; 320 records of patients
      in spontaneous or induced labor who received epidural analgesia were included in
      the analysis. Patients with a contraindication to labor, antepartum fetal death,
      or twins were excluded. Maternal demographics, cervical examination at epidural
      placement, epidural medication characteristics, and labor and delivery data were
      abstracted from medical records. Station was characterized as high if the fetal
      vertex was above the level of the maternal ischial spines or low if the vertex
      was at or below the level of the ischial spines at the time of epidural
      placement. RESULTS: The relative risk of occiput malposition was significantly
      increased with epidural placement at high station. This risk remained after we
      controlled for age and birth weight. Cervical dilatation was not independently
      associated with occiput position at delivery. CONCLUSIONS: Epidural placement
      before engagement of the fetal head is associated with an increased incidence of
      malposition at delivery. This finding may provide an insight into the empiric
      observation that operative delivery is variably increased for patients laboring
      under epidural anesthesia.

PMID- 8885763
TI  - Abnormal nuchal findings on screening ultrasonography: aneuploidy stratification
      on the basis of ultrasonographic anomaly and gestational age at detection.
AB  - OBJECTIVE: Our purpose was to determine the specific likelihood of different
      aneuploidies by gestational age in patients with nuchal folds and simple and
      septated nuchal membranes. STUDY DESIGN: Retrospective database analysis was
      performed of 158 consecutive patients with a nuchal fold or simple or septated
      nuchal membrane on either abdominal or vaginal ultrasonography. RESULTS: Thirty
      eight patients with nuchal folds, 65 with simple nuchal membranes, and 55 with
      septated nuchal membranes were evaluated. Septated nuchal membranes were
      associated with the highest incidence of karyotypic abnormalities (> 50%). A peak
      incidence of trisomy 21 (27%) was found in the early midtrimester, leveling off
      to 11% by the late midtrimester. The late first trimester had a high incidence of
      trisomy 18 (22%), occurring more frequently than 45,X. CONCLUSION:
      Ultrasonographic anomalies in the posterior neck are associated with aneuploidy
      from 21% to 58% of the patients in this selected population. Each anomaly has
      different risks for aneuploidy type, varying with gestational age at diagnosis.

PMID- 8885765
TI  - Effect of parity correction on Down syndrome detection by the multiple-marker
      screening test.
AB  - OBJECTIVE: Our purpose was to determine whether maternal parity affects analyte
      levels in the multiple-marker screening test for Down syndrome and to derive a
      correction factor and determine its effect on Down syndrome detection and screen
      positive rates. STUDY DESIGN: Our database consisted of 3039 multiple-marker
      screening test results and corresponding fetal karyotypes (2983 euploid and 56
      Down syndrome). Cases were grouped by maternal parity as follows: 0 (n = 848), 1
      (n = 1140), or > or = 2 (n = 1051). The mean multiple of the median of maternal
      serum alpha-fetoprotein, estriol, and human chorionic gonadotropin was determined
      for each group. A correction factor was derived for each parity group and applied
      to the database. Parity-corrected Down syndrome detection rates and screen
      positive rates were determined. RESULTS: Parity significantly affected the mean
      multiple of the median of human chorionic gonadotropin levels (p = 0.0001) but
      did not affect the values for estriol or maternal serum alpha-fetoprotein.
      Application of a parity correction factor for human chorionic gonadotropin
      increased the Down syndrome detection rate in women who had two or more
      pregnancies from 71% to 82% without increasing the overall screen-positive rate.
      CONCLUSION: Human chorionic gonadotropin levels are significantly lower in
      multiparous women. Correcting human chorionic gonadotropin for maternal parity
      increases Down syndrome detection for women who had two or more pregnancies
      without affecting the overall screen-positive rate.

PMID- 8885764
TI  - Faint and positive amniotic fluid acetylcholinesterase with a normal sonogram.
AB  - OBJECTIVE: Both faint and positive amniotic fluid acetylcholinesterase
      determinations have been associated with fetal abnormalities. We evaluated the
      effect of a normal sonogram and positive or faint acetylcholinesterase level on
      the risk for anomalies. STUDY DESIGN: Between Jan. 1, 1989, and Feb. 1, 1995,
      4859 amniocenteses were performed. Twenty-three cases of abnormal
      acetylcholinesterase determinations combined with normal sonograms were
      identified, and pregnancy outcomes were determined. RESULTS: One abnormal
      karyotype was identified (45,X/47,XXX mosaic). No neural tube defects were seen
      in infants with an abnormal acetylcholinesterase determination and normal
      sonogram. One fetus of a twin pregnancy had a ventral wall defect that was not
      detected on ultrasonography. Seventy-three percent of infants were normal at
      birth, but 27% of the pregnancies had abnormal outcomes. CONCLUSIONS: Advances in
      ultrasonography have led to improved detection of fetal abnormalities. With a
      normal karyotype, repeat invasive testing may not be necessary.

PMID- 8885766
TI  - Prospective evaluation of the antenatal incidence and postnatal significance of
      the fetal echogenic cardiac focus: a case-control study.
AB  - OBJECTIVE: We evaluated the antenatal incidence and postnatal significance of
      echogenic cardiac foci observed during antenatal ultrasonography. STUDY DESIGN:
      During a 4-month period, all women undergoing dating ultrasonography between 16.0
      and 24.9 weeks' gestation at one referral center were prospectively evaluated for
      an echogenic cardiac focus during an apical four-chamber view of the heart.
      Referrals for maternal or fetal complications were excluded. Postnatal
      echocardiography was performed for those identified with positive findings.
      Controls were selected from among normal subjects in the general group for
      comparison with the study group. RESULTS: Five hundred six consecutive fetuses
      were evaluated at a mean +/- SD gestational age of 20.6 +/- 1.6 weeks. There were
      25 (4.9%) fetuses found to have echogenic cardiac focus (left ventricle = 19,
      right ventricle = 6). Echocardiography was performed between 0.3 and 20.1 weeks
      postdelivery. After birth, 12 echogenic left ventricle papillary muscles and
      three echogenic left ventricle chordae were identified; there were no postnatal
      right ventricle findings. There were no cases of intracardiac tumor or myocardial
      dysfunction; one neonate had minor structural malformations. There were no
      significant differences in maternal age, gravidity, parity, gestational age at
      ultrasonography, gestational age at delivery, or 5-minute Apgar scores. A
      significant difference was observed in birth weight between the control (n = 50)
      and study (n = 25) groups (3465 +/- 501 gm vs 3124 +/- 589 gm; p = 0.002). This
      difference persisted after correcting for gestational age, although all infants
      in both groups born after 37.0 weeks weighed > 2500 gm. CONCLUSIONS: The
      incidence of echogenic cardiac foci during routine midtrimester ultrasonography
      is 4.9%. As an isolated finding, the echogenic cardiac focus may be associated
      with a statistically significant but clinically insignificant decrease in birth
      weight. Because of these findings, we consider an isolated echogenic cardiac
      focus in a patient at low risk for cardiac abnormalities a variant of normal,
      which does not warrant follow-up clinical evaluation.

PMID- 8885768
TI  - Serial amniotic fluid index in severe preeclampsia: a poor predictor of adverse
      outcome.
AB  - OBJECTIVE: The purpose of the study was to determine the relationship between low
      amniotic fluid index and intrauterine growth restriction and nonreassuring fetal
      testing in patients with severe preeclampsia. STUDY DESIGN: We reviewed the
      medical records of 136 women with severe preeclampsia managed conservatively for
      at least 48 hours. Patients were followed up with a daily nonstress test and
      amniotic fluid index. We evaluated amniotic fluid index < or = 5 cm and < or = 7
      cm, measured on admission or just before delivery (i.e., final), and attempted to
      correlate these findings with the incidence of nonreassuring fetal testing
      necessitating cesarean section or the incidence of intrauterine growth
      restriction (birth weight < or = 10th percentile). RESULTS: One hundred seven
      patients had a cesarean section, but only 42 (39%) of these were for a
      nonreassuring fetal heart rate tracing or a persistent biophysical profile of <
      or = 4, and 38 (36%) of the pregnancies resulted in infants with intrauterine
      growth restriction. During expectant management, the amniotic fluid index
      worsened for 61 (45%) patients and improved or remained the same for 75 (55%).
      For those with an amniotic fluid index of < or = 5 cm both on admission and at
      delivery, there was a significantly higher incidence of intrauterine growth
      restriction compared with those with an amniotic fluid index > 5 cm (p = 0.007
      and p = 0.029, respectively). However, there was no association between
      intrauterine growth restriction and an amniotic fluid index < or = 7 cm.
      Moreover, there was no difference in the frequency of nonreassuring fetal heart
      rate testing on the basis of amniotic fluid volume (p = 0.59) or intrauterine
      growth restriction (p = 0.4). CONCLUSIONS: For women with severe preeclampsia
      remote from term, an amniotic fluid index < or = 5 cm is predictive of
      intrauterine growth restriction but lacks sensitivity. There is no association
      between the amniotic fluid index status and frequency of cesarean section for
      fetal distress or nonreassuring fetal testing.

PMID- 8885767
TI  - Evaluation of nitric oxide as a mediator of severe preeclampsia.
AB  - OBJECTIVE: Our purpose was to determine whether a reduction in nitric oxide
      synthesis occurs in women with severe preeclampsia as a consequence of soluble
      serum factors. STUDY DESIGN: Circulating nitrate and nitrite levels were compared
      between women who met standard clinical criteria for severe preeclampsia (n = 21)
      and maternal or gestational age-matched, normotensive, primagravid control
      subjects (n = 21). End-products of nitric oxide synthesis were measured from
      venous blood samples using nitrate reduction and chemiluminescence. To detect in
      vitro suppression of nitric oxide synthesis, human umbilical vein endothelial
      cell monolayers were grown to confluence and exposed to culture media containing
      20% severe preeclamptic or control sera. Nitrate and nitrite production were
      compared in duplicate monolayers for each experimental condition, expressed as
      means +/- SEM in picomoles per 10(6) cells. Data were compared by Student's t or
      Mann-Whitney U tests, when appropriate, along with Spearman correlations for
      comparisons of laboratory and clinical data. RESULTS: Circulating nitrate and
      nitrite levels were similar in normotensive and preeclamptic cohorts (976 +/- 88
      vs 1009 +/- 41 pmol/ml, respectively; p = 0.22), and no correlations between
      blood pressure and nitric oxide metabolite levels were observed for the control
      or severely preeclamptic subsets. Similar patterns of in vitro endothelial
      nitrite production were observed after 1-, 12-, and 24-hour incubations with 20%
      control or preeclamptic sera. CONCLUSIONS: Circulating nitrate and nitrite levels
      are not reduced in patients with severe preeclampsia compared with normotensive
      controls, and sera from these women do not suppress endothelial cell nitric oxide
      synthesis in vitro.

PMID- 8885769
TI  - Dietary consumption and plasma concentrations of vitamin E in pregnancies
      complicated by preeclampsia.
AB  - OBJECTIVE: Vitamin E, a potent antioxidant, has been suggested to play a role in
      preventing preeclampsia. Our aim was to determine whether consumption and plasma
      levels of vitamin E are lower in the preeclamptic than in normal women. STUDY
      DESIGN: A case-control study design was used. We identified 48 women with
      preeclampsia (late-pregnancy hypertension, proteinuria, and hyperuricemia).
      Ninety normal women served as the control group. Vitamin E consumption was
      estimated by use of a previously validated dietary recall questionnaire
      administered by a single trained research nurse to 42 of the preeclamptic women
      and all 90 of the control women. Blood was drawn from all women and stored until
      assayed at -70 degrees C. Plasma vitamin E concentrations were determined by use
      of high-pressure liquid chromatography. RESULTS: The mean dietary vitamin E
      consumption was similar for both the preeclamptic and control group (11.74 +/-
      9.39 vs 11.34 +/- 7.51 mg/24 hr, p = 0.73). When the analysis also included
      estimations of vitamin E supplements, the total consumption was found to be
      higher in those who had preeclampsia than in controls (37.20 +/- 20.54 vs 22.3 +/
      27.24 mg/24 hr, p = 0.003). The mean plasma vitamin E concentration was
      significantly higher in preeclamptic than in control patients (1.41 +/- 0.39 vs
      1.15 +/- 0.32 mg/dl, p < 0.001). Among the preeclamptic patients, those with
      severe disease associated with HELLP (hemolysis, elevated liver enzymes, and low
      platelets) syndrome (n = 11) had the highest plasma vitamin E concentrations.
      CONCLUSIONS: We found no evidence that low vitamin E consumption is related to
      the development of preeclampsia. Higher plasma vitamin E concentrations in
      preeclamptic patients are speculated to represent a response to oxidative stress.

PMID- 8885770
TI  - Multiple gestations from in vitro fertilization: successful implantation alone is
      not associated with subsequent preeclampsia.
AB  - OBJECTIVE: Our purpose was to compare the risk for preeclampsia and severe
      preeclampsia in triplet and twin gestations and to evaluate the effect of
      successful implantation on the development of preeclampsia and on perinatal
      outcome in triplet pregnancies conceived by means of in vitro fertilization.
      STUDY DESIGN: A case control study was conducted of triplet pregnancies (n = 38)
      matched for maternal age, parity, race, and delivery date with twin pregnancies
      (n = 38) resulting from a single fetal reduction (spontaneously or by means of
      multifetal pregnancy reduction) after successful implantation of triplets. All
      pregnancies were conceived by means of in vitro fertilization. Rates of
      preeclampsia and other maternal complications, factors affecting implantation,
      and perinatal outcomes were compared. Preeclampsia and severe preeclampsia were
      defined by The American College of Obstetricians and Gynecologists criteria. The
      Student t test and the chi(2) test were used for statistical analysis. RESULTS:
      The triplet group had a higher rate of severe preeclampsia (26.3%) than the twin
      (reduced triplet) group (7.9%). The prevalence of preeclampsia (mild and severe
      combined) also was higher among the triplet group (44.7%) than among the twin
      group (15.8%). There was no difference in other maternal complications of
      pregnancy or in factors potentially affecting implantation, such as assisted
      hatching. Mean fetal weight was lower among the triplet group, but gestational
      age at delivery was not significantly different. CONCLUSIONS: The rate of
      preeclampsia is higher among triplets conceived by means of in vitro
      fertilization than among triplets conceived by means of in vitro fertilization
      and reduced to twins. This finding suggests that fetal number, placental mass, or
      factors unrelated to the success of implantation are more important to the
      development of preeclampsia than is successful implantation alone.

PMID- 8885771
TI  - Reduction of right atrial peak systolic velocity in growth-restricted discordant
      twins.
AB  - OBJECTIVE: The objective of this study was to measure blood flow velocity changes
      through the tricuspid valve in intrauterine growth-restricted twins. STUDY
      DESIGN: Discordant twins were evaluated by measurement of tricuspid valve flow
      velocities. Twin pairs with one intrauterine growth-restricted fetus caused by
      uteroplacental insufficiency and one appropriately grown fetus were included in
      the analysis. Fetuses with chromosomal or structural abnormalities and confirmed
      twin-twin transfusion syndrome were excluded. Eighteen pairs met these criteria.
      Student's t test was used for comparison of flow velocities. RESULTS: Peak
      ventricular diastolic flow velocities through the tricuspid valve in the twin
      with intrauterine growth restriction and the appropriately grown twin were 35.8
      +/- 4.43 cm/sec and 34.0 +/- 6.7 cm/sec, respectively (p = 0.35). The atrial peak
      systolic flow velocity values were 42.1 +/- 1.2 and 50.3 +/- 1.2, respectively (p
      = 0.049). CONCLUSIONS: The velocity of blood flow through the tricuspid valve
      during atrial systole is lower in growth-restricted twins than in appropriately
      grown cotwins when growth restriction is caused by uteroplacental insufficiency.
      Its potential in differentiating discordancy from the other causes remains to be
      explored.

PMID- 8885772
TI  - Group B Streptococcus and preterm premature rupture of membranes: a randomized,
      double-blind clinical trial of antepartum ampicillin.
AB  - OBJECTIVE: Our purpose was to determine whether ampicillin prolongs the latency
      period after preterm premature rupture of membranes in patients colonized with
      group B Streptococcus. STUDY DESIGN: Sixty patients presenting at < or = 35
      weeks' gestation with preterm premature rupture of membranes were included in the
      study. Cervical, vaginal, and perianal cultures for group B premature rupture
      were obtained. The participants then were randomized to receive either ampicillin
      or placebo intravenously for 24 hours and then orally until hospital discharge or
      delivery. All patients were treated without the use of tocolytic drugs. The
      chi(2) test, Fisher exact test, Student t test, and Wilcoxon signed-rank test
      were used for statistical analysis when appropriate. RESULTS: Fifteen patients
      had cultures positive for group B Streptococcus. Patients with cultures positive
      for group B Streptococcus who received ampicillin (n = 8) were more likely not to
      have been delivered of their infants 48 hours after preterm premature rupture of
      membranes than patients who received placebo (n = 7), a statistically significant
      difference (100% vs 43%; p = 0.01; relative risk 2.3; 95% confidence interval 1.2
      to 4.5). Seven days after preterm premature rupture of membranes, however, there
      was no significant difference in percentage of patients with cultures positive
      for group B Streptococcus who remained undelivered (63% vs 29%; p = 0.19;
      relative risk, 2.2; 95% confidence interval 0.7 to 7.1). Among patients with
      cultures negative for group B Streptococcus, there was a trend for patients who
      received ampicillin to remain undelivered 48 hours after preterm premature
      rupture of membranes compared with those who received placebo, but the difference
      was not statistically significant (87% vs 64%; p = 0.07; relative risk, 1.4; 95%
      confidence interval 1.0 to 1.9). There also was no difference in percentage of
      patients with cultures negative for group B Streptococcus who remained
      undelivered 7 days after preterm premature rupture of membranes 39% vs 27%; p =
      0.40; relative risk, 1.4; 95% confidence interval 0.61 to 3.3). There were no
      differences between the treatment and placebo arms of the group B Streptococcus
      positive and negative cohorts in incidence of cesarean section, chorioamnionitis,
      postpartum endometritis, or neonatal infectious morbidity. CONCLUSION: Use of
      antibiotics increases the percentage of patients with cultures positive for group
      B Streptococcus who remain undelivered 48 hours after preterm premature rupture
      of membranes. Antibiotic therapy may provide a window of opportunity for maternal
      treatment with corticosteroids to decrease the risk for neonatal morbidity among
      these preterm gestations.

PMID- 8885773
TI  - Effect of dual tocolysis on the incidence of severe intraventricular hemorrhage
      among extremely low-birth-weight infants.
AB  - OBJECTIVE: Our purpose was to evaluate the null hypothesis that dual tocolysis
      with magnesium sulfate and indomethacin does not alter the rate of grade III or
      IV intraventricular hemorrhage. STUDY DESIGN: Fifty-six neonates weighing 500 to
      800 gm from mothers who received tocolytic therapy with magnesium sulfate alone
      or in combination with indomethacin were the subjects of this retrospective
      study. Demographic variables were evaluated with a Student t test, chi(2)
      analysis, Fisher exact test, or Mantel-Haenszel chi(2) as appropriate. RESULTS:
      There was an increased incidence of grade III to IV intraventricular hemorrhage
      among patients treated with dual therapy (p = 0.02). Logistic regression showed
      that fetal age and dual tocolysis with indomethacin were the only independent
      prognostic factors for severe intraventricular hemorrhage. CONCLUSION: The
      results indicate that dual tocolysis with indomethacin may place extremely low
      birth-weight infants at increased risk for grade III to IV intraventricular
      hemorrhage.

PMID- 8885774
TI  - The preterm prediction study: risk factors in twin gestations. National Institute
      of Child Health and Human Development Maternal-Fetal Medicine Units Network.
AB  - OBJECTIVE: Our purpose was to determine the association between the presence of
      bacterial vaginosis, fetal fibronectin, and a short cervix and the risk of
      spontaneous preterm birth of twins. STUDY DESIGN: We prospectively screened 147
      women with twins at 24 and 28 weeks' gestation for more than 50 potential risk
      factors for spontaneous preterm birth. We also measured cervical length with
      ultrasound scans and tested for the presence of bacterial vaginosis. Fetal
      fibronectin level was evaluated every 2 weeks from 24 to 30 weeks' gestation.
      Outcomes included spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37
      weeks. RESULTS: Among twin as compared with singleton pregnancies, a cervical
      length < or = 25 mm was more common at both 24 and 28 weeks, a statistically
      significant difference. There were no significant differences in most other risk
      factors. Of the factors evaluated by means of univariate analysis at 24 weeks,
      only a short cervix (< or = 25 mm) was consistently associated with spontaneous
      preterm birth. The odds ratio and 95% confidence interval for spontaneous preterm
      birth at < 32 weeks, < 35 weeks, and < 37 weeks were 6.9 (2.0 to 24.2), 3.2 (1.3
      to 7.9), and 2.8 (1.1 to 7.7). At 28 weeks, a cervical length < or = 25 mm was
      not a strong predictor of spontaneous preterm birth. At both 28 weeks (odds
      ratio, 9.4; confidence interval, 1.0 to 67.7) and 30 weeks (odds ratio 46.1;
      confidence interval, 4.2 to 1381), a positive fetal fibronectin result was
      significantly associated with spontaneous preterm birth at < 32 weeks. Bacterial
      vaginosis at 24 or 28 weeks was not associated with spontaneous preterm birth of
      twins. Multivariate analysis confirmed the association between cervical length <
      or = 25 mm at the 24-week visit and spontaneous preterm birth and also confirmed
      that at 24 weeks the other risk factors were less consistently and often not
      statistically significantly associated with spontaneous preterm birth. Of the
      risk factors evaluated at 28 weeks, only a positive fetal fibronectin was
      associated with a significantly increased risk for spontaneous preterm birth.
      CONCLUSIONS: Most known risk factors for spontaneous preterm birth were not
      significantly associated with spontaneous preterm birth of twins. At 24 weeks,
      cervical length < or = 25 mm was the best predictor of spontaneous preterm birth
      at < 32 weeks, < 35 weeks, and < 37 weeks. Of the risk factors evaluated at 28
      weeks, fetal fibronectin was the only statistically significant predictor of
      spontaneous preterm birth at < 32 weeks.

PMID- 8885775
TI  - Value of fetal fibronectin as a predictor of preterm delivery for a low-risk
      population.
AB  - OBJECTIVE: We examined clinical value of cervical fetal fibronectin detection by
      a quantitative enzyme-linked immunosorbent assay as a predictor of preterm
      delivery in a population (n = 111) of middle-class pregnant women considered to
      be at low risk for preterm delivery. STUDY DESIGN: In this prospective study,
      fetal fibronectin samples from cervicovaginal secretions were obtained biweekly
      from 24 to 34 weeks' gestation. RESULTS: Twenty-two (20%) patients had at least
      one positive fetal fibronectin test result. Eleven women (10%) were delivered
      spontaneously at < 37 weeks; seven of these had at least one positive fetal
      fibronectin test result (positive predictive value = 31.8%, sensitivity = 63.6).
      An additional three women were delivered prematurely because of other obstetric
      indications, and all had negative fetal fibronectin test results. The remaining
      15 patients with at least one positive fetal fibronectin test result were
      delivered at term (> or = 37 weeks). Of the seven women with positive fetal
      fibronectin results who were delivered prematurely, five were delivered within 2
      weeks of obtaining a positive result. However, there were no obvious clinical
      discriminators between true-positive and false-positive fetal fibronectin
      results. Eighty-nine women tested negative, and 85 of these women were delivered
      at term (specificity = 82.0%). The negative predictive value of fetal fibronectin
      as a predictor of term delivery in this low-risk population is 96.6%, with odds
      ratio = 8.8 (95% confidence interval 1.9 to 40.3), relative risk = 6.9 (95%
      confidence interval 1.8 to 26.6), and Fisher Exact Test p = 0.007. CONCLUSIONS:
      Although negative biweekly fetal fibronectin determinations for prediction of
      preterm delivery in this low-risk obstetric population correlate well with the
      absence of preterm delivery, they are of limited clinical value for the
      prediction of preterm birth.

PMID- 8885776
TI  - Interleukin-10 inhibition of interleukin-6 in human amniochorionic membrane:
      transcriptional regulation.
AB  - OBJECTIVE: Our purpose was to study the regulatory effects of recombinant
      interleukin-10 on interleukin-6 messenger ribonucleic acid and protein production
      by human fetal membranes. STUDY DESIGN: Amniochorionic membranes were collected
      from women undergoing elective cesarean section. Membranes were maintained in an
      organ explant system and stimulated with media containing lipopolysaccharide (50
      ng/ml) and various amounts of recombinant interleukin-10 (10, 50, 100 ng/ml).
      Experiments were conducted in a dose- and time-dependent manner. Transcription
      and translation of interleukin-6 were monitored with quantitative reverse
      transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay.
      RESULTS: Interleukin-10 stimulation of amniochorionic membranes in culture
      produced a dose-dependent decrease in the production of interleukin-6 messenger
      ribonucleic acid and protein. Quantitative polymerase chain reaction was used to
      document a decrease in interleukin-6 messenger ribonucleic acid, which paralleled
      the decrease in peptide levels as detected with enzyme-linked immunosorbent
      assay. The interleukin-10 effect was present only when tissue was concurrently
      stimulated with lipopolysaccharide. Interleukin-10 inhibition could not be
      produced in the absence of lipopolysaccharide stimulation. CONCLUSION: Addition
      of interleukin-10 to culture media leads to transcriptional regulation of
      interleukin-6, which results in decreased production of both messenger
      ribonucleic acid and protein by human amniochorionic membranes. The decrease in
      interleukin-6 is a dose-dependent effect of interleukin-10. This finding may have
      important implications with respect to a possible role for interleukin-10 or an
      interleukin-10 stimulatory factor in the management of preterm labor associated
      with the presence of inflammatory cytokines.

PMID- 8885777
TI  - Amniotic fluid index predicts the relief of variable decelerations after
      amnioinfusion bolus.
AB  - OBJECTIVE: Our purpose was to determine whether intrapartum amniotic fluid index
      before amnioinfusion can be used to predict response to therapeutic
      amnioinfusion. STUDY DESIGN: Intrapartum patients (n = 85) with repetitive
      variable decelerations in fetal heart rate that necessitated amnioinfusion (10
      ml/min for 60 minutes) underwent determination of amniotic fluid index before and
      after bolus amnioinfusion. The fetal heart tracing was scored (scorer blinded to
      amniotic fluid index values) for number and characteristics of variable
      decelerations before and 1 hour after initiation of amnioinfusion. The
      amnioinfusion was considered successful if it resulted in a decrease of > or =
      50% in total number of variable decelerations or a decrease of > or = 50% in the
      rate of atypical or severe variable decelerations after administration of the
      bolus. Spontaneous vaginal births before completion of administration of the
      bolus (n = 18) were excluded from analysis. The probability of success of
      amnioinfusion in relation to amniotic fluid index was analyzed with the chi(2)
      test for progressive sequence. RESULTS: The mean amniotic fluid index before
      amnioinfusion was 6.2 +/- 3.3 cm. An amniotic fluid index of < or = 5 cm was
      present in 40% of patients (27/67), and an amniotic fluid index of < or = 8 cm
      was present in 72% of patients (48/67). The probability of success of
      amnioinfusion decreased with increasing amniotic fluid index before amnioinfusion
      (76% [16/21] when initial amniotic fluid index was 0 to 4 cm, 63% [17/27] when
      initial amniotic fluid index was 4 to 8 cm, 44% [7/16] when initial amniotic
      fluid index was 8 to 12 cm, and 33% [1/3] when initial amniotic fluid index was >
      12 cm, p = 0.03). The incidence of nuchal cords or true umbilical cord knots
      increased in relation to amniotic fluid index before amnioinfusion. CONCLUSIONS:
      Amniotic fluid index before amnioinfusion can be used to predict the success of
      amnioinfusion for relief of variable decelerations in fetal heart rate. Failure
      of amnioinfusion at a high amniotic fluid index before amnioinfusion may be
      explained by the increased prevalence of nuchal cords or true knots in the
      umbilical cord.

PMID- 8885778
TI  - Fetal pulse oximetry and visual on-line signal identification in the second stage
      of labor.
AB  - OBJECTIVE: To determine the accuracy of reflection pulse oximetry and visual on
      line signal identification during the second stage of labor. STUDY DESIGN: The
      reflection pulse oximetry system used allows visual on-line identification of
      valid signals by showing the original red and infrared signals. With this system
      oxygen saturation measurements are averaged over nine heartbeats only. An
      atraumatic suction probe was used. The measurements of the last 10 minutes before
      delivery were compared with umbilical venous cord blood samples taken soon after
      delivery. RESULTS: The correlation between reflection pulse oximetry readings
      during the last 10 minutes before delivery and umbilical vein oxygen saturation
      was significant (r = 0.45; p < 0.0005). Standard regression analysis showed R2 of
      0.45. This did not change if weighted by the rate of valid signals (R2 = 0.42).
      If the predelivery loss of valid signals was less than 5 minutes, the correlation
      improved (r = 0.47, p < 0.001). Umbilical vein pH did not correlate with pulse
      oximetry readings. CONCLUSION: The reflection pulse oximetry system used allows
      visual on-line identification of even short periods of valid signals and reflects
      actual oxygen saturation in fetal arterial blood.

PMID- 8885779
TI  - Nicked free beta-subunit and Down syndrome screening.

PMID- 8885780
TI  - A possible chemotherapeutic response by paclitaxel and other antineoplastic
      agents in treatment of choriocarcinoma in vitro.

PMID- 8885781
TI  - Does intraamniotic infection in the early phase of the second trimester really
      exist?

PMID- 8885782
TI  - Zinc deficiency and abnormal fetal development: assessment of maternal or fetal
      zinc status.

PMID- 8885783
TI  - Minilaparotomies with a new special instrument.

PMID- 8885784
TI  - Why WIC (Women, Infants and Children Food Supplement Program)?

PMID- 8885785
TI  - Trial of labor after low vertical cesarean section.

PMID- 8885786
TI  - Infertility in beta-thalassemia major.

PMID- 8885787
TI  - Abnormal triple-test result plus normal ultrasonographic results equal
      amniocentesis?

PMID- 8885788
TI  - Association between second-trimester bacterial invasion of amniotic fluid and
      spectrophotometry at 450 nm.

PMID- 8885789
TI  - Reconsider unipolar methods for female sterilization.

PMID- 8885790
TI  - Group B streptococci and pregnancy.

PMID- 8885791
TI  - Incident and demographic trends in cervical neoplasia.
AB  - During the past several years, information has been published that suggests that
      preinvasive cervical neoplasia may be increasing in the United States. Part of
      the increase can be explained by changes in disease definition, in disease
      reporting, and in screening patterns. However, a small increase may have occurred
      in certain population subsets.

PMID- 8885792
TI  - A brief synopsis of the role of human papillomaviruses in cervical
      carcinogenesis.
AB  - The expansion of our knowledge in the realms of pathology, epidemiology, and
      molecular biology of human papillomaviruses (HPV) has defined them as the major
      and best understood class of true human tumor viruses. The interaction of the
      papillomavirus genome with its host cell produces the majority of cytologic
      abnormalities at which cervical cancer screening is directed. The epidemiologic
      pattern of HPV infection accounts for the established association of cervical
      neoplasia with sexual activity. The molecular interactions of the HPV genome with
      its host cell suggest a plausible mechanism for its carcinogenic action. This
      presentation will succinctly review current knowledge of HPV biology to
      facilitate an understanding of the clinical significance of this virus.

PMID- 8885793
TI  - Natural history of cervical neoplasia: overview and update.
AB  - Current cervical cancer control strategies and specifically, the screening and
      treatment policies that have been used during the past 30 years, are based on an
      understanding of the natural history of cervical neoplasia that does not take
      into account the important role of human papillomavirus in cervical cancer
      pathogenesis. This survey presents a review of new data on the causes of cervical
      cancer and the role of human papillomavirus and recommends the integration of
      these data. Incorporation of new information on the role of human papillomavirus
      as the causative agent of most cervical cancers will allow the design of more
      efficient and more cost-effective strategies for cervical cancer control.

PMID- 8885794
TI  - Rapidly progressive cervical cancer: the Connecticut experience.
AB  - A review is presented of 15 years of clinical experience working with women who
      developed cervical cancer within a short interval after the last reported
      negative Papanicolaou smear. Our initial report concerned isolated cases in which
      women were diagnosed with invasive cervical cancer within 1 year of a reported
      normal Papanicolaou smear. Our second report focused on a 10-year review of the
      Yale-New Haven Hospital experience, during which 40 of 555 women had rapidly
      progressive invasive disease; 35 cases (87.5%) occurred in women younger than 40
      years old and almost all of the 40 diagnosed because of persistent symptoms
      despite a recent normal Papanicolaou smear. Our final experience is a population
      based study of all women in Connecticut who developed cervical cancer between
      1985 and 1990. A total of 118 of 481 (24.5%) participants were diagnosed with
      cervical cancer within 3 years of their last true-negative Papanicolaou smear.
      Adenocarcinomas occurred in 38 cases (32.2%). These data suggest that rapidly
      occurring cervical cancer may be a manifestation of endocervical carcinomas that
      have been inadequately screened.

PMID- 8885795
TI  - Cytopathology of false negatives preceding cervical carcinoma.
AB  - The Papanicolaou smear has been a remarkably effective tool in cancer prevention,
      but it is not a perfect test. Although the most important factor in failure of
      cervical cancer prevention is lack of adequate screening, other factors include
      problems with sampling, interpretation, and effective clinical follow-up. A small
      number of rapidly developing cervical cancers probably also arise in the interval
      between Papanicolaou smear screenings. Consequently, cervical cancer will develop
      in some women despite appropriate screening. This article will analyze some of
      the problems relating to diagnostic errors, which include abnormal cells that are
      few (< 100), small, or bland.

PMID- 8885796
TI  - Reducing false negatives in clinical practice: the role of neural network
      technology.
AB  - The fact that some cervical smears result in false-negative findings is an
      unavoidable and unpredictable consequence of the conventional (manual
      microscopic) method of screening. Errors in the detection and interpretation of
      abnormality are cited as leading causes of false-negative cytology findings;
      these are random errors that are not known to correlate with any patient risk
      factor, which makes the false-negative findings a "silent" threat that is
      difficult to prevent. Described by many as a labor-intensive procedure, the
      microscopic evaluation of a cervical smear involves a detailed search among
      hundreds of thousands of cells on each smear for a possible few that may indicate
      abnormality. Investigations into causes of false-negative findings preceding the
      discovery of high-grade lesions found that many smears had very few diagnostic
      cells that were often very small in size. These small cells were initially
      overlooked or misinterpreted and repeatedly missed on rescreening. PAPNET testing
      is designed to supplement conventional screening by detecting abnormal cells that
      initially may have been missed by microscopic examination. This interactive
      system uses neural networks, a type of artificial intelligence well suited for
      pattern recognition, to automate the arduous search for abnormality. The
      instrument focuses the review of suspicious cells by a trained cytologist.
      Clinical studies indicate that PAPNET testing is sensitive to abnormality
      typically missed by conventional screening and that its use as a supplemental
      test improves the accuracy of screening.

PMID- 8885797
TI  - Atypical squamous cells of undetermined significance and low-grade squamous
      intraepithelial lesion: diagnostic criteria and management.
AB  - Since institution of the Bethesda system for reporting cervical and vaginal
      smears, there has been an increase in the number of smears reported to
      demonstrate atypical squamous cells of undetermined significance and low-grade
      squamous intraepithelial lesions. The cytologic changes associated with a smear
      reported to have these cells are discussed. It is apparent that the
      interpretation of the cellular changes defined as atypical squamous cells of
      undetermined significance are not clear and that there is a significant variation
      among cytopathologists as to the cytologic changes that should be incorporated
      under this classification. Data are presented on the frequency of this diagnosis
      in our laboratory and of the follow-up findings observed in a subgroup of
      patients whose smears were reported to demonstrated atypical squamous cells of
      undetermined significance. The cytologic and histopathologic changes observed
      with smears reported as demonstrating findings compatible with a low-grade
      squamous intraepithelial lesion are also discussed. A follow-up algorithm for the
      management of such patients is presented.

PMID- 8885798
TI  - Impact of therapy for cervical intraepithelial neoplasia on fertility.
AB  - Cervical intraepithelial neoplasia is endemic in young American women. Because
      the majority of these women have a strong desire to maintain fertility, the
      efficacy of treatment modalities for this condition must be weighed against
      potential negative effects on fertility. Except for cone biopsy, however, the
      peer-reviewed literature provides little information about the effects of such
      techniques on fertility. While there are no data demonstrating that the other
      commonly used therapies (loop electrical excision procedure, cryotherapy, laser
      vaporization, and diathermy cautery) have a negative impact on fertility, neither
      has it been definitively proved that they do not have an untoward impact on
      fertility. Thus further studies are needed, and patients should be educated
      regarding the limitations of available information when informed consent for
      treatment is obtained.

PMID- 8885799
TI  - Changing strategies in the treatment of allergic rhinitis.

PMID- 8885800
TI  - Inhaled drugs for treatment of asthma: nothing is ever as simple as it seems.

PMID- 8885801
TI  - Global increases in allergic respiratory disease: the possible role of diesel
      exhaust particles.
AB  - OBJECTIVE: Reading this article will enable the readers to recognize and evaluate
      i e potential relationship between allergic respiratory disease and polyaromatic
      hydrocarbons as air pollutants from industrial and automotive fuel sources. In
      this article we review the long-term trends in the prevalence of allergic airway
      diseases (rhinitis and asthma). We then examine the epidemiologic and other
      research data relating to the role that hydrocarbon fuel emissions may have had
      on allergic respiratory disease. DESIGN: Published literature on the relationship
      between specific air pollutants and trends in allergic respiratory disease were
      reviewed. Reports of research on pollutant effects on allergic antibody (IgE)
      were also studied. In both cases, the Melvyl-Medline database since 1975 was used
      for literature searches. Older references were identified from the bibliographies
      of relevant articles and books and with the help of the rare books collection at
      UCLA's Louis M. Darling Biomedical library. RESULTS: Examination of the
      historical record indicates that allergic rhinitis and allergic asthma have
      significantly increased in prevalence over the past two centuries. Although the
      reasons for this increase are not fully elucidated, epidemiologic data suggest
      that certain pollutants such as those produced from the burning of fossil fuels
      may have played an important role in the prevalence changes. Also important are
      studies showing that diesel exhaust, a prototypical fossil fuel, is able to
      enhance in vitro and in vivo IgE production. CONCLUSION: Increased levels of the
      compounds resulting from fossil fuel combustion may be partly responsible for the
      increased prevalence of allergic respiratory disease. If the nature of these
      compounds and the mechanisms by which they exacerbate allergic disease can be
      identified, steps can be taken to reduce the production or the impact of these
      allergy producing compounds.

PMID- 8885802
TI  - Quinolone allergy?

PMID- 8885803
TI  - Efficacy and safety of triamcinolone acetonide aqueous nasal spray in patients
      with seasonal allergic rhinitis.
AB  - BACKGROUND: In order to accommodate increasing patient preferences a new aqueous
      formulation of triamcinolone acetonide nasal spray was developed for the relief
      of symptoms associated with seasonal and perennial allergic rhinitis. OBJECTIVE:
      This multicenter, randomized, double-blind study was designed to compare the
      efficacy and safety of once-daily triamcinolone acetonide aqueous nasal spray
      (220 micrograms/day) with placebo in relieving the symptoms of seasonal allergic
      rhinitis due to ragweed. METHODS: One hundred forty patients received either a
      once daily 220-microgram dose of triamcinolone acetonide aqueous nasal spray or
      placebo for 2 weeks. Patients evaluated the severity of seasonal allergic
      rhinitis symptoms daily for 2 weeks according to a 4-point scale (0 = absent, 1 =
      mild, 2 = moderate, 3 = severe). Physician and patient global evaluations of
      overall treatment effectiveness were assessed at the end of the treatment period.
      RESULTS: Patients receiving triamcinolone acetonide aqueous nasal spray, 220
      micrograms/day, had significantly (P < .05) greater improvements in all rhinitis
      symptoms at weeks 1 and 2 and overall for the 2-week treatment period compared
      with the placebo group. A significant (P = .006) improvement in the nasal index
      occurred as early as 12 hours after the first dose of triamcinolone acetonide
      aqueous nasal spray. Both patients and physicians reported a greater overall
      improvement in symptoms for the triamcinolone acetonide aqueous nasal spray
      group. There were no differences between the two treatment groups in the
      incidence of adverse events. CONCLUSIONS: This study confirmed that a 220
      microgram dose of triamcinolone acetonide aqueous nasal spray, administered once
      daily for 2 weeks, is well tolerated and reduces effectively the severity of
      symptoms of seasonal allergic rhinitis due to ragweed.

PMID- 8885804
TI  - Effect of immunotherapy on sCD23 levels in patients allergic to Hymenoptera
      venom.
AB  - BACKGROUND: sCD23 is the designation given to the low affinity IgE receptor. The
      soluble fragment of this receptor (sCD23) participates in the regulation of IgE
      synthesis. OBJECTIVE: The purpose of this study is to examine the effect of a
      venom immunotherapy regimen on sCD23 levels. METHODS: We measured sCD23 levels by
      ELISA in Hymenoptera venom-allergic patients (positive skin tests and a history
      of systemic reactions to Hymenoptera sting) in serial sera collected over a
      course of venom immunotherapy with a mean duration of 54 months. Mean pre-sCD23
      and post-sCD23 levels were compared using a Student's two-tailed t test. RESULTS:
      sCD23 levels were found to be unchanged over the course of venom immunotherapy.
      CONCLUSIONS: This is the first longitudinal study that has been done. It suggests
      that while both immunotherapy and sCD23 are known to be involved in the
      regulations of IgE synthesis in the atopic patient, the immunomodulation seen in
      venom immunotherapy is not mediated through sCD23 in any simple regulatory
      manner.

PMID- 8885805
TI  - Idiopathic anaphylaxis: a series of 335 cases.
AB  - BACKGROUND: Idiopathic anaphylaxis is anaphylaxis with no definable etiology and
      no trigger by exogenous allergens. Initially described in 1978, idiopathic
      anaphylaxis has been subsequently characterized and treatment protocols have been
      established. OBJECTIVE: The demographics and course of 335 patients (225
      previously reported) treated with prednisone, hydroxyzine, and albuterol are now
      reported. RESULTS: Ages ranged from 5 to 83 years. There were nine new pediatric
      patients in this series totaling 14 (4.2%). Atopy was common (48%) with 34 new
      patients with asthma. The duration of symptoms prior to presentation ranged from
      three days to 27 years. One hundred thirty-two patients with idiopathic
      anaphylaxis were available for follow-up. Twenty of these are currently receiving
      prednisone for control of idiopathic anaphylaxis, seven of them as part of their
      initial therapy, and ten for control of recurrence of symptoms. Three patients
      required continuous alternate day prednisone for control of symptoms
      (corticosteroid-dependent idiopathic anaphylaxis). Of the 335 patients, there
      were no longer any patients with the diagnosis of malignant idiopathic
      anaphylaxis defined as requiring prednisone, 20 mg daily, or 60 mg every other
      day, for control of idiopathic anaphylaxis. Of the six patients previously
      diagnosed with malignant idiopathic anaphylaxis, five no longer required
      prednisone and one has a decreased prednisone requirement of 20 mg on alternate
      days. Hospital visits were significantly reduced by the management regimens.
      There were no fatalities from idiopathic anaphylaxis in this series. CONCLUSIONS:
      The incidence of idiopathic anaphylaxis is increasing in our practice with more
      patients being evaluated each year. During 1104 patient years of observation (the
      longest period of single patient observation being 24 years), no inciting agent
      has been found responsible for the anaphylactic symptoms. Prognosis continues to
      remain good with the majority of patients achieving remission with
      pharmacotherapy.

PMID- 8885807
TI  - Bean bag allergy revisited: a case of allergy to inhaled soybean dust.
AB  - BACKGROUND: Soybean is a common food allergen. It can cause Type 1 allergy (IgE
      mediated) symptoms from its ingestion, as well as from inhalation of its dust.
      OBJECTIVE: To report a case of allergy in a child from the inhalation of soybean
      dust from a bean bag and the course of this allergy over time. METHODS: Case
      report; routine skin testing and laboratory tests; bean bag challenge studies;
      special studies with saline extracts of the bean bag soybeans. RESULTS: A 6-year
      old boy with a 1-year history of allergic rhinitis noted symptoms of urticaria,
      eyelid angioedema, and mild respiratory distress while at school playing with a
      bean bag containing soybeans. Skin tests revealed positive reactions to
      commercial soybean extract and bean bag soybean extracts. Bean bag challenge was
      also positive. The patient's serum was able to transfer this sensitivity by the
      Prausnitz-Kustner (P-K) reaction. RAST and polystyrene tube radioimmunoassay
      techniques, however, did not detect specific IgE to soybean allergens. During
      follow-up, the patient developed allergy symptoms with ingestion of other beans.
      This latter allergy lasted for only 2 years, but the bean bag allergy was still
      present 4 years later (bean bag challenge). The patient returned at age 19 for
      recurrence of his allergic rhinitis and de novo asthma. Repeat bean bag challenge
      at age 24 was negative. CONCLUSIONS: To the best of our knowledge, this is the
      first reported childhood case of IgE-mediated allergy from soybean dust during
      play with a bean bag containing dry soybeans. Over time, despite the loss of this
      sensitivity, he developed asthma, another IgE-mediated illness.

PMID- 8885806
TI  - A comparison of bronchodilator responses to albuterol delivered by ultrasonic
      versus jet nebulization in moderate to severe asthma.
AB  - BACKGROUND: Nebulization of beta-agonists is preferred as a mode of treatment in
      moderate to severe asthma. Few studies, however, have compared its use in this
      population using an ultrasonic versus a jet nebulizer. OBJECTIVE: The purpose of
      the study was to compare bronchodilator responses to albuterol between an
      ultrasonic and a jet nebulizer in moderate to severe asthma. METHODS: Fifteen
      stable, moderately to severely asthmatic patients were randomized to receive the
      ultrasonic or jet nebulizer for 2 weeks. They were then crossed over for an
      additional 2 weeks. Albuterol was the agent used. The bronchodilator response was
      measured at baseline, and up to four hours after treatment with each nebulizer.
      Daily peak flows were then done for 2 weeks. RESULTS: The maximal percentage of
      increase in FEV1 at 30 minutes using the ultrasonic nebulizer was 39.9 +/- 8% (P
      < 0.001) versus 25.1 +/- 7.6% (P = .005) using the jet nebulizer. There were no
      other differences between the ultrasonic and the jet nebulizer in FEV1 or FVC
      during the 4-hour spirometry. During the home trial, the difference in evening
      PEFR between the jet nebulizer (69.05 +/- 14.9 L/min) and the ultrasonic
      nebulizer (90.11 +/- 18.7 L/min) was significant (P = .04). CONCLUSIONS: In
      summary, the ultrasonic and the jet nebulizer produced comparable bronchodilator
      responses to albuterol in stable moderately to severely asthmatic patients.

PMID- 8885808
TI  - Incidence and prevalence of physician-diagnosed asthma in a suburban population
      of young adults.
AB  - BACKGROUND: Asthma is a common chronic disease of both children and adults, but
      there have been few reports of the incidence of asthma in well defined adult
      populations. OBJECTIVE: To determine the incidence and prevalence of asthma in a
      population of young adults living in suburban Detroit. METHODS: As part of a
      study of the development of allergic disease in children, the parents of 841
      study children, from a defined, well characterized population, were questioned
      about their personal histories of allergic disease, including asthma, during the
      mother's pregnancy. The children have been followed from birth until 4 years of
      age. When the child became 4, the parents were again questioned about allergic
      disease. Those reporting asthma when the child was 4 but not prior to the child's
      birth, were recontacted to confirm that they had been diagnosed by a physician as
      having asthma in the 4-year interval. Because of prior reports concerning racial
      differences in the prevalence of asthma and the small number of non-white mothers
      in the study population, calculations of asthma prevalence and incidence were
      limited to the 760 mothers, who described themselves and their baby's father as
      white. RESULTS: The parents studied were young adults mean age 28.7 [(standard
      deviation (SD) 4.5 years] and 31.0 (SD 5.0) years, of mothers and fathers,
      respectively. These parents were relatively well educated with 30.7% of mothers
      and 43.5% of fathers having college degrees. The initial prevalence of a previous
      physician diagnosis of asthma was 7.5% [95% confidence interval (95% CI) = 5.7
      9.6] in the mothers and 6.9% (95% CI = 5.2-9.0) in the fathers, yielding a total
      prevalence of 7.2% (95% CI = 5.9-8.7) in these 1484 adults. Five hundred thirty
      three mothers and 498 fathers (total = 1031), who did not report asthma during
      the mothers' pregnancies, were available for questioning when the children were 4
      years old. The average yearly incidence of asthma was 5.2 (95% CI = 2.6-9.2) per
      1000 in the mothers and 1.5 (95% CI = 0.3-4.4) per 1000 in the fathers (P =
      .058), with an overall incidence of 3.4 (95% CI = 1.8-5.7) per 1000. The average
      yearly incidence was 5.3/1000 in those < 30 years old and 1.5/1000 in those > or
      = 30 years of age (P = .056). CONCLUSIONS: We conclude that the incidence of
      asthma in this population of relatively young, well educated, white adults is
      approximately 3.4 per 1000 per year and that newly diagnosed asthma was more
      common in women and in those < 30 years of age.

PMID- 8885809
TI  - Effect of cetirizine on antigen-induced tracheal contraction of passively
      sensitized guinea pigs.
AB  - BACKGROUND: Cetirizine dihydrochloride (cetirizine), a potent histamine H1
      receptor antagonist, has been developed as an anti-allergy drug. OBJECT: The anti
      allergic effects and mechanism of cetirizine were studied using in vitro assay
      systems. METHODS: We investigated the effect of cetirizine on antigen-induced
      contractions of isolated tracheal strips and on chemical mediator release from
      antigen-stimulated lung chips taken from passively sensitized guinea pigs. We
      examined the antigen-induced mobilization of Ca2+ in MC/9 mast cells sensitized
      with IgE. RESULTS: Cetirizine inhibited the antigen-induced contraction of
      isolated guinea-pig trachea concentration dependently. Pyrilamine, another
      histamine H1-receptor antagonist, delayed the response but did not change the
      maximum amplitude. Cetirizine at the concentration of 3 microM also inhibited the
      antigen-induced release of histamine, leukotriene D4, and leukotriene E4 from
      guinea pig lung chips. Furthermore, it inhibited the antigen-induced Ca2+
      increase in MC/9 mast cells, whereas pyrilamine did not. CONCLUSION: These
      findings suggest that one anti-allergic mechanism of cetirizine may inhibit
      mediator release which is, at least partially, mediated by a decrease in the
      transient Ca2+ influx in mast cells.

PMID- 8885810
TI  - Modulation of histamine release by sodium, potassium adenosine triphosphatase
      inhibition.
AB  - BACKGROUND: Previous studies have shown that a sodium, potassium adenosine
      triphosphatase inhibitor is present in the plasma of allergic subjects in whom
      enhanced histamine releasability has also been reported. PURPOSE: The purpose of
      this study was to determine the effect of in vitro sodium, potassium adenosine
      triphosphatase inhibition on whole blood histamine release. METHODS: Samples
      obtained from 12 patients with allergic rhinitis and 12 nonallergic subjects were
      incubated in duplicate for 30 minutes with anti-IgE antibody (100 micrograms/mL)
      or control buffer following a 0-, 10-, 20-, 30-, 60-, 120- and 180-minute
      preincubation with ouabain (3.0 mM) or diluent. Cell supernatants were assayed
      for histamine by radioimmunoassay and results were expressed as a percentage of
      total histamine release. RESULTS: Mean (+/- 1 SEM) anti-IgE induced release, in
      the presence and absence of ouabain, respectively, for allergic subjects was 27.5
      +/- 5.5 and 21.0 +/- 4.5 (ten minutes, P < 0.05), 30.3 +/- 6.0 and 22.4 +/- 4.8
      (20 minutes, P < .025), 28.9 +/- 5.2 and 23.5 +/- 4.1 (30 minutes), 33.8 +/- 7.1
      and 26.7 +/- 5.4 (60 minutes, P < .05), 43.2 +/- 7.5 and 24.3 +/- 4.6 (120
      minutes, P < .001), and 34.5 +/- 5.0 and 29.8 +/- 5.4% (180 minutes). Spontaneous
      histamine release in allergic subjects was also significantly increased by
      ouabain. Mean (+/- SEM) spontaneous release, in the presence and absence of
      ouabain, respectively, for allergic subjects was 2.0 +/- 0.5 and 0.9 +/- 0.2 (60
      minutes, P < .025), 2.8 +/- 0.5 and 1.9 +/- 0.4 (120 minutes, P < .05), and 5.4
      +/- 1.5 and 3.9 +/- 0.8% (180 minutes, P < .005). Ouabain did not significantly
      alter histamine release in non-allergic subjects. CONCLUSIONS: These data show
      that ouabain induced a significant increase in both spontaneous and induced
      histamine release in allergic subjects. In vivo, sodium, potassium adenosine
      triphosphatase inhibition may have an effect on histamine release in allergic
      subjects.

PMID- 8885811
TI  - Prevalence of sensitization to food allergens in adult Swedes.
AB  - BACKGROUND: The results from a population study on respiratory symptoms and
      bronchial hyperresponsiveness in relation to symptoms of food intolerance and
      sensitization to food allergens are reported. METHODS: The study included 1,812
      men and women, aged 20 to 44 years and residents in three areas of Sweden who
      participated in the European Community Respiratory Health Survey. The prevalence
      of IgE sensitization to egg white, fish, wheat, peanut, soy, and milk was assayed
      by CAP-RAST and the prevalence of symptoms of food intolerance was determined by
      a standardized questionnaire. RESULTS: The study group included a random sample
      of 1,397 subjects from the general population at the three centers. Of these, 85
      (6%) had specific IgE antibodies to one of the food allergens and 345 (25%)
      reported symptoms of food intolerance. After enrichment with subjects suffering
      from symptoms of asthma, the sample included a total of 1,812 individuals of
      which 144 subjects had specific IgE antibodies to one or more of the food
      allergens studied. Of these 144, 52% reported food intolerance but only 16%
      related the symptoms to any of the food allergens in the panel. Sensitization to
      food allergens was more common in atopic subjects, subjects reporting current
      asthma, and subjects with bronchial hyperresponsiveness (P < .001). These
      associations remained significant after adjustment for the degree of allergic
      sensitization, whether defined as the number of positive skin prick tests or as
      total serum IgE levels. CONCLUSIONS: Although sensitization to food allergens is
      not uncommon in adults, the correlation to specific symptoms of food intolerance
      is weak. Sensitization to food allergens may have special relevance to asthma and
      bronchial hyperresponsiveness.

PMID- 8885812
TI  - Prevalence and diagnosis of celiac disease in IgA-deficient children.
AB  - BACKGROUND: Reported frequencies of celiac disease in selective IgA deficiency in
      childhood vary widely and this is probably due to the different characteristics
      of the patients studied and to the different criteria used for intestinal biopsy:
      all patients or only those with symptoms of malabsorption. Diagnosis of celiac
      disease is of considerable importance in IgA deficiency because of its increased
      frequency and also because avoidance of dietary gluten permits elimination of the
      symptoms and complications of celiac disease. OBJECTIVES: To obtain a more
      reliable estimate of the incidence of celiac disease in childhood IgA deficiency
      jejunal biopsies were performed in 65 consecutively diagnosed IgA-deficient
      children whose parents consented. Some clinical and laboratory parameters
      including IgA-antigliadin and IgG-antigliadin antibodies were evaluated to
      predict their usefulness in selecting IgA-deficient patients for intestinal
      biopsy. METHODS: All IgA-deficient patients had serum IgA levels below 5 mg/dL
      and salivary IgA below 0.5 mg/dL. Jejunal biopsy was performed using a peroral
      Watson capsule and IgA-antigliadin and IgG-antigliadin antibodies were performed
      by an ELISA assay. RESULTS: Biopsy findings of severe villous atrophy permitted
      diagnosis of celiac disease in 7.7% (5/65 children). IgG-antigliadin antibody
      levels, elevated in 16 patients including all five celiacs, were the best
      parameter for predicting celiac disease and gave no false negatives. CONCLUSIONS:
      The 7.7% frequency of celiac disease observed in these IgA-deficient children is
      about 20 times higher than in the general Italian population, and the lowest
      among the studies biopsying all patients; this is probably attributable to the
      presence of a substantial proportion of healthy children (20/65) and very few
      (2/65) with autoimmune disorders. The elevated sensitivity and negative
      predictive value of IgG-antigliadin antibodies lead us to suggest that positive
      IgG-antigliadin antibodies can be used to select IgA-deficient children for
      jejunal biopsy with a very low probability of missing celiac disease while
      allowing a drastic reduction in the number of biopsies performed.

PMID- 8885813
TI  - Homeopathy revisited.

PMID- 8885814
TI  - Treatment guidelines for patients with thyroid nodules and well-differentiated
      thyroid cancer. American Thyroid Association.
AB  - A set of minimum clinical guidelines for use by primary care physicians in the
      evaluation and management of patients with thyroid nodules or thyroid cancer was
      developed by consensus by an 11-member Standards of Care Committee (the authors
      of the article) of the American Thyroid Association, New York, NY. The
      participants were selected by the committee chairman and by the president of the
      American Thyroid Association based on their clinical experience. The committee
      members represented different geographic areas within the United States, to
      reflect different practice patterns. The guidelines were developed based on the
      expert opinion of the committee participants, as well as on previously published
      information. Each committee participant was initially assigned to write a section
      of the document and to submit it to the committee chairman, who revised and
      assembled the sections into a complete draft document, which was then circulated
      among all committee members for further revision. Several of the committee
      members further revised and refined the document, which was then submitted to the
      entire membership of the American Thyroid Association for written comments and
      suggestions, many of which were incorporated into a final draft document, which
      was reviewed and approved by the Executive Council of the American Thyroid
      Association.

PMID- 8885815
TI  - Clinical implications of Barrett's esophagus.
AB  - Barrett's esophagus is a medical condition in which the squamous mucosa that
      normally lines the distal esophagus is replaced by a columnar type of epithelium.
      Most definitions that have been used for inclusion of patients in studies have
      indicated that columnar mucosa must extend 3 cm or more above the
      gastroesophageal junction. The precise length refers to the distance above the
      manometrically defined lower esophageal sphincter. This measurement is somewhat
      cumbersome to make on a routine basis for all patients at the time of endoscopy
      and thus is generally not done. It is important to realize that the
      gastroesophageal junction can be visually identified at the area where the
      esophagus tapers, in the region of the lower esophageal sphincter. The tapering
      of the esophagus in the region of the lower esophageal sphincter may be difficult
      to determine when lower esophageal sphincter pressures are low; thus, we commonly
      say that Barrett's esophagus is defined as columnar mucosa 3 cm above the region
      where the gastric folds end.

PMID- 8885816
TI  - Leukotrienes in asthma. The potential therapeutic role of antileukotriene agents.
AB  - Recent advances in research have led to the identification of an inflammatory
      component to asthma. Although many endogenous mediators are involved in
      inflammation, leukotrienes appear to play an especially important role in asthma.
      The leukotrienes produce tissue edema, mucus secretion, and smooth-muscle
      proliferation, along with a powerful bronchoconstriction. In addition,
      antileukotriene drugs have emerged as potential therapeutic agents for asthma.
      This study was designed to review the current information on these new agents. In
      this review, full-length articles of antileukotriene agents are examined. These
      articles were found through MEDLINE under the following medical headings: asthma,
      inflammation, leukotriene, leukotriene-receptor antagonist, and leukotriene
      synthesis inhibitor. Most clinical studies cited are placebo-controlled trials
      involving healthy individuals and patients with asthma. These studies indicate
      that antileukotriene agents improve lung function and reduce the symptoms of
      asthma and the need for additional medication. Drugs that inhibit leukotriene
      receptor binding and leukotriene synthesis hold promise as new additions to the
      armamentarium of clinicians who treat asthma. Furthermore, these drugs have
      already helped to elucidate some details of the pathophysiological features of
      asthma.

PMID- 8885817
TI  - Exercise-associated amenorrhea, low bone density, and estrogen replacement
      therapy.
AB  - BACKGROUND: Women with exercise-associated amenorrhea have a higher frequency of
      osteoporosis than eumenorrheic runners and sedentary women. The use of hormone
      replacement therapy was suggested many years ago to increase bone density in
      exercising women with amenorrhea and low bone density. OBJECTIVE: To determine if
      hormone replacement therapy increased bone density in women with exercise
      associated amenorrhea. METHODS: We performed a retrospective clinical study
      comparing the changes in bone density in 8 women runners who took hormone
      replacement therapy with 5 who refused medication but who were followed up as
      controls over 24 to 30 months. RESULTS: Vertebral and femoral neck bone density
      significantly increased by 8.0% +/- 1.2% (+/- SEM) and 4.1% +/- 0.3% (+/- SEM),
      respectively, in 8 women runners with amenorrhea taking 24 to 30 months of
      estrogen replacement therapy with progestational support. Control women not
      taking replacement therapy had nonsignificant decreases of less than 2.5% at each
      site. CONCLUSION: Hormone replacement therapy appears to increase bone density in
      amenorrheic runners.

PMID- 8885818
TI  - Cost of breast cancer treatment. A 4-year longitudinal study.
AB  - OBJECTIVE: To determine the longitudinal cost of the treatment of patients with
      breast cancer. METHODS: An analysis was performed of 200 women with 205 newly
      diagnosed breast cancers during 1989 in a health maintenance organization
      population (US Healthcare, Blue Bell, Pa). Medical records and claims data were
      analyzed for the total costs of medical care during the 4-year period after
      diagnosis. The costs over time were analyzed for clinical stage and use of
      mammography screening. RESULTS: The total costs of medical care during the 4-year
      period after diagnosis were strongly related to clinical stage at diagnosis, with
      higher total costs for patients with stages III to IV at diagnosis compared with
      patients with stages 0 to II at diagnosis. The cost for all stages of disease
      declined after years 1 to 2, with the exception of stage II, which increased
      slightly in years 3 to 4. The use of screening mammography was associated with a
      significant decrease in the cost of medical care during the 4-year study period.
      CONCLUSIONS: The goal of mammography screening programs should be to achieve
      downstaging to stages 0 to 1 to achieve reduction in breast cancer mortality and
      to reduce the overall consumption of health care resources for the treatment of
      breast cancer. These cost data should be considered within the framework of
      future cost-effective analysis for screening mammography programs.

PMID- 8885819
TI  - Do pulmonary radiographic findings at presentation predict mortality in patients
      with community-acquired pneumonia?
AB  - BACKGROUND: Previous studies have reported conflicting results on whether
      pulmonary radiographic findings predict mortality for patients with community
      acquired pneumonia (CAP). OBJECTIVE: To determine whether pulmonary radiographic
      findings at presentation are independently associated with 30-day mortality in
      patients with suspected CAP. METHODS: This study was conducted as part of the
      Pneumonia Patient Outcomes Research Team multicenter, prospective cohort study of
      ambulatory and hospitalized patients with clinical and radiographic evidence of
      CAP. For each patient with CAP, a structured data form was completed by a panel
      of radiologists to evaluate the radiographic pattern of infiltrate, number of
      lobes involved, presence of pleural effusion, and 8 other radiographic
      characteristics. Cox proportional hazards models were used to evaluate the
      independent association between radiographic findings and 30-day mortality, while
      controlling for patient demographic, clinical, and laboratory characteristics
      with a known association with this outcome. RESULTS: Of 2287 patients enrolled in
      the Pneumonia Patient Outcomes Research Team cohort study, 1906 patients (83.3%)
      had a pulmonary radiographic infiltrate confirmed by the radiology panel.
      Overall, 30-day mortality in this cohort was 4.9%. Univariate regression analyses
      demonstrated the following radiographic characteristics to be significantly
      associated with 30-day mortality: (1) bilateral pleural effusions (risk ratio
      [RR], 7.0; 95% confidence interval [CI], 3.9-12.6); (2) a pleural effusion of
      moderate or greater size (RR, 3.4; 95% CI, 1.4-8.4); (3) 2 or more lobes involved
      with infiltrate (RR, 2.5; 95% CI, 1.6-3.8); (4) bilateral infiltrate (RR, 2.8;
      95% CI, 1.9-4.2); (5) bronchopneumonia (RR, 1.6; 95% CI, 1.0-2.7); and (6) air
      bronchograms (RR, 0.5; 95% CI, 0.2-0.9). Multivariate analysis of radiographic
      features and other clinical characteristics showed the presence of bilateral
      pleural effusions (RR, 2.8; 95% CI, 1.4-5.8) was independently associated with
      mortality. CONCLUSIONS: In patients with CAP, the presence of bilateral pleural
      effusions is an independent predictor of short-term mortality. This finding,
      which is available at presentation, can help guide physicians' assessment of
      prognosis in CAP.

PMID- 8885820
TI  - Estrogen replacement therapy and risk of Alzheimer disease.
AB  - BACKGROUND: With Alzheimer disease emerging as a major public health problem, the
      identification of factors that might prevent this disease are important. Estrogen
      loss associated with menopause may contribute to the development of Alzheimer
      disease. OBJECTIVE: To evaluate the effects of different estrogen preparations,
      varying dosages of estrogen, and duration of estrogen replacement therapy on the
      risk of Alzheimer disease in postmenopausal women. STUDY DESIGN AND METHODS: A
      case-control study nested within a prospective cohort study of residents of
      Leisure World Laguna Hills, a retirement community in Southern California. The
      cohort comprised 8877 women who were first mailed a health survey in 1981. Of the
      3760 female cohort members who died between 1981 and 1995, 248 women with
      Alzheimer disease or other dementia diagnoses likely to represent Alzheimer
      disease (senile dementia, dementia, or senility) mentioned on the death
      certificate were identified. Five controls were individually matched to each case
      according to year of death and year of birth (+/- 1 year). RESULTS: The risk of
      Alzheimer disease and related dementia was significantly reduced in estrogen
      users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49
      0.88). The risk was reduced for both oral and nonoral (i.e., injections and/or
      creams) routes of administration. The risk decreased significantly with both
      increasing dosages (P = .01) and increasing duration (P = .01) of oral therapy
      with conjugated equine estrogen, the most commonly used estrogen preparation.
      Within each dose category, the risk decreased with increasing duration of
      therapy, with the lowest observed risk in long-term users who received high doses
      (odds ratio, 0.48; 95% confidence interval, 0.19-1.17). CONCLUSION: This study
      suggests that estrogen replacement therapy may be useful for preventing or
      delaying the onset of Alzheimer disease in postmenopausal women.

PMID- 8885821
TI  - How useful is thyroid function testing in patients with recent-onset atrial
      fibrillation? The Canadian Registry of Atrial Fibrillation Investigators.
AB  - BACKGROUND: Patients with recent-onset atrial fibrillation often undergo routine
      thyroid function screening to rule out thyroid disease as a cause of atrial
      fibrillation. METHODS: Patients with recent (< 3 months) onset of documented
      atrial fibrillation or flutter were enrolled in the Canadian Registry of Atrial
      Fibrillation from outpatient clinics, emergency departments, and hospital wards
      across Canada. Seven hundred twenty-six patients underwent baseline thyroid
      function screening and were assessed for presence of clinical thyroid disease.
      Serum thyrotropin level (TSH) was measured in 707 patients (97%), and thyroxine
      level (T4) in 407 patients (56%). RESULTS: A TSH level less than 0.1 mU/L was
      present in 5 patients (0.7%). A TSH level less than normal but more than 0.1 mU/L
      was present in 34 patients (4.7%). No patient had definite hypothyroidism (TSH >
      20 mU/L), but 56 patients (7.7%) had an elevated TSH level that was less than 20
      mU/L. During 1.7 years of follow-up, only 7 patients were found to have clinical
      hyperthyroidism, and 11 patients (1.5%) had hypothyroidism. Logistic regression
      analysis showed that palpitations (odds ratio, 4.9; 95% confidence interval, 1.7
      14.0) and asymptomatic presentation (odds ratio, 5.5; 95% confidence interval,
      1.9-16.2) were risk factors for low TSH level, and increasing age (odds ratio,
      1.32 every 10 years; 95% confidence interval, 1.01-1.66) was a risk factor for
      high TSH level. The positive predictive value of palpitations and asymptomatic
      presentation for low TSH level were 9% and 8%, respectively. CONCLUSIONS: An
      abnormal TSH level is common in patients with recent-onset atrial fibrillation.
      However, clinical thyroid disease is uncommon. Routine TSH screening of patients
      who have atrial fibrillation has a low yield and may be better applied to those
      patients at higher risk of having undiagnosed clinical thyroid disease.

PMID- 8885822
TI  - Immunogenicity of a recombinant hepatitis B vaccine in adults.
AB  - OBJECTIVES: To evaluate the immunogenicity and reactogenicity of a recombinant
      hepatitis B vaccine in health care staff under routine use and unselected
      conditions and to investigate factors that influence the response to vaccination.
      METHODS: This prospective postmarketing surveillance study was performed in
      unselected health care staff and their relatives (age range, 12-60 years) at 58
      hospitals. Overall, 880 subjects were administered a 20-microgram dose of a
      vaccine at 0, 1, and 6 months according to the prescribing information and under
      routine hospital practice, and they were tested for antibody to hepatitis B
      surface antigen after the third dose at the hospitals routine laboratory. The
      principal outcome measures were antibody to hepatitis B surface antigen titers
      that were expressed as the seroprotection rate (SPR) (SPR [given as a
      percentage], > or = 10 mlU/ mL), spontaneously reported adverse events, and
      geometric mean titers (in milli-international units per milliliter). RESULTS: The
      compliance to the 3-dose schedule under routine hospital practice was 98.1%. The
      immune response was good in all age groups, and the overall SPR was 97.8% at 1
      month after the third dose in field conditions with unselected health care
      workers. The SPR in vaccinees (age range, 40-59 years) was close to 95%. Age (P <
      .001), smoking (> or = 10 cigarettes per day) (P < .001), Broca index (> 110%) (P
      < .001), antibody to hepatitis B surface antigen testing (> 8 weeks after the
      last dose) (P = .03), chronic underlying disease (P = .04), and male gender (P =
      .04) were factors associated with lower geometric mean titers in routine vaccine
      use. No serious adverse events were reported. CONCLUSION: The large immune
      response that was elicited by this hepatitis B vaccine in adults under daily
      routine field conditions reflected reality, with a high SPR also found in elderly
      and other persons with risk factors associated with a lower immune response.

PMID- 8885823
TI  - Depressive affect and survival among gay and bisexual men infected with HIV.
AB  - BACKGROUND: Although depression has been related to chronic disease processes and
      outcomes, studies examining the relationship between depression and disease
      progression in persons with human immunodeficiency virus (HIV) infection have
      produced inconsistent results. OBJECTIVE: To investigate whether depressive
      affect is associated with HIV mortality. METHODS: This was a prospective cohort
      study (San Francisco Men's Health Study) using a population based probability
      sample of single men living in areas of San Francisco, Calif, with high case
      rates of acquired immunodeficiency syndrome. Data collection was at 6-month
      intervals with up to 15 waves of follow-up. Subjects included all 402 homosexual
      or bisexual men who in July 1984 had serologic evidence of HIV infection and who
      survived a minimum of 1 wave after baseline. Depressive affect was measured at
      each wave with the affective subscale of the Center for Epidemiologic Studies
      Depression Scale. Laboratory markers, World Health Organization staging,
      antiretroviral use, and hospitalizations were also used as predictor variables.
      The primary outcome measure was survival. RESULTS: In a Cox proportional hazards
      model, a time-dependent measure of depressive affect was associated with greater
      mortality (adjusted risk ratio, 1.67; 95% confidence interval, 1.01-2.78).
      CONCLUSIONS: Depressive affect was associated with mortality risk, highlighting
      the importance of diagnosis and treatment of depression among HIV-infected gay
      and bisexual men. Replication of this effect in incident cohorts with well
      characterized dates of HIV infection is needed and, if replicated, an exploration
      of mediating pathways suggested.

PMID- 8885824
TI  - Attitudes of elderly patients and their families toward physician-assisted
      suicide.
AB  - OBJECTIVES: To examine and compare attitudes of elderly outpatients and their
      families toward physician-assisted suicide (PAS), explore sociodemographic and
      health correlates of these attitudes, assess family members' ability to predict
      patients' attitudes toward PAS, and determine family members' ability to agree on
      these predictions. SUBJECTS AND METHODS: Elderly patients with medical and
      psychiatric problems (n = 168; mean age, 75.8 years) who were attending a
      geriatrics specialty clinic, along with accompanying family members (n = 146),
      were systematically surveyed on their attitudes toward PAS in case of terminal
      illness, chronic illness, and mental incompetence. Relatives were also asked to
      predict patients' responses to items on the questionnaire. Patients and relatives
      were blinded to each others' responses. RESULTS: Favorable attitudes toward PAS
      were reported by 39.9% of the patients and 59.3% of the relatives (P < .001) in
      case of terminal illness, 18.2% and 25.3%, respectively, in case of chronic
      illness, 13.5% and 15.4%, respectively, in case of mental incompetence, and 34.0%
      and 55.6% (P < .001), respectively, for legalization of PAS. Family members
      showed a marginal ability to predict patients' attitudes toward PAS with kappa
      values of agreement that ranged from 0.09 to 0.41. Family members also had
      difficulty agreeing with each other on how they thought patients would respond
      (range of kappa values, 0.18-0.47). Patients who opposed PAS were women, black
      individuals, and those with less education, low incomes, and dementia or
      cognitive impairment. CONCLUSIONS: While many frail elderly patients favored PAS
      in cases of terminal illness, the proportion that opposed it was significantly
      higher than that among relatives; relatives, in turn, displayed only a marginal
      ability either to predict patients' attitudes or to agree among themselves.
      Patients who oppose PAS represent a particularly vulnerable element of society
      (elderly persons, women, black individuals, and poor, uneducated, and demented
      persons), and such patients may warrant special protection.

PMID- 8885825
TI  - Human immunodeficiency virus-related oral manifestations and gender. A
      longitudinal analysis. The University of California, San Francisco Oral AIDS
      Center Epidemiology Collaborative Group.
AB  - BACKGROUND: Because human immunodeficiency virus (HIV) infection affects an
      increasing number of women in the United States, we investigated the role played
      by gender in the occurrence of HIV-related oral conditions. METHODS: As part of a
      4-year prospective study of 3 epidemiological cohorts, oral and physical
      examinations (including blood tests) were performed on HIV-infected men (n = 200)
      and women (n = 218) at 6-month intervals. Our outcome variables included oral
      conditions commonly associated with HIV infection: hairy leukoplakia,
      candidiasis, ulcers, warts, non-Hodgkin lymphoma, Kaposi sarcoma, and parotid
      enlargement. RESULTS: Only hairy leukoplakia, candidiasis, and ulcers were
      observed. The occurrence of hairy leukoplakia and candidiasis was higher in men
      (22% and 24%, respectively) than in women (9% and 13%, respectively) during the
      study period. A regression model for longitudinal data (generalized estimating
      equation) disclosed that the odds of having hairy leukoplakia were 2.5 times
      higher for men than for women, after controlling for CD4+ cell count, race, and
      injecting drug use (95% confidence interval, 1.34-4.76; P = .003). Length of
      follow-up did not confound this association. A weaker association was found
      between the occurrence of oral candidiasis and gender (adjusted odds ratio, 1.85;
      95% confidence interval, 1.0-3.43; P = .05). CONCLUSIONS: In this sample of HIV
      infected adults, we found that men were significantly more likely to have hairy
      leukoplakia than were women. The hairy leukoplakia-gender association merits
      further investigation, because it may be related to a gender difference in the
      mode of expression of Epstein-Barr virus.

PMID- 8885826
TI  - A prospective study of cigarette smoking and the risk of pancreatic cancer.
AB  - OBJECTIVES: To prospectively examine the excess incidence of pancreatic cancer
      among cigarette smokers and to examine the influence of smoking cessation on the
      risk of pancreatic cancer. METHODS: We obtained data on cigarette smoking and
      other risk factors for pancreatic cancer from 118,339 women aged 30 to 55 years
      and 49,428 men aged 40 to 75 years who were without diagnosed cancer. During the
      2,116,229 persons-years of follow-up, pancreatic cancer was diagnosed in 186
      participants. RESULTS: The multivariate relative risk of pancreatic cancer for
      current smokers was 2.5 (95% confidence interval, 1.7-3.6). A significant,
      positive trend in risk with increasing pack-years of smoking was observed (P for
      trend = .004), although this association was confined to cigarette consumption
      within the past 15 years. Compared with participants who continued to smoke,
      former smokers had a 48% reduction in pancreatic cancer risk within 2 years of
      quitting. Ultimately, the relative risk of pancreatic cancer among former smokers
      approached that for never smokers after less than 10 years of smoking cessation.
      Overall, the proportion of pancreatic cancers attributable to cigarette smoking
      was 25%. CONCLUSIONS: Cigarette smoking is associated with an increased risk of
      pancreatic cancer. The rapid reduction in risk associated with quitting suggests
      that smoking cessation could eliminate 25% of the 27,000 deaths from pancreatic
      cancer occurring annually in the United States.

PMID- 8885827
TI  - Efficacy of the National Cholesterol Education Program Step I diet: a randomized
      trial incorporating quick-service foods.

PMID- 8885828
TI  - Rhinocerebral mucormycosis: cure without surgery?

PMID- 8885829
TI  - Identification of adenine binding domain peptides of the NADP+ active site within
      porcine heart NADP(+)-dependent isocitrate dehydrogenase.
AB  - Photoaffinity labeling with [2'-32P]2N3NADP+ and [32P]2N3NAD+ was used to
      identify two overlapping tryptic and chymotryptic generated peptides within the
      adenine binding domain of NADP(+)-dependent isocitrate dehydrogenase (IDH).
      Photolysis was required for insertion of radiolabel, and prior photolysis of
      photoprobes before addition of IDH prevented insertion. Photoincorportion of
      2N3NAD+ inhibited the enzymatic activity of IDH. Photolabeling of IDH with both
      [32P]2N3NAD+ and [2'-32P]2N3-NADP+ showed saturation effects with apparent Kds of
      20 and 14 microM (+/-12%), respectively. The efficiency of photoincorporation at
      saturation of binding sites was determined to be about 50%. Also, photolabeling
      was observed with [32P]8N3ATP and [32P]2N3ATP but with saturation effects
      observed at lower affinity. With all radiolabeled probes reduction of
      photoinsertion was effected best by the addition of NADP+ followed by NAD+ and
      then ATP, indicating that photoinsertion with all the probes was within the NADP+
      binding site. Isolation of [32P]2N3NAD+ and [2'-32P]2N3NADP+ photolabeled
      peptides by use of immobilized boronate and immobilized Al3+ chromatography,
      respectively, followed by HPLC purification resulted in the identification of
      overlapping peptides corresponding to Ile244-Arg249 and Leu121-Arg133 (tryptic
      fragments) and Lys243-His248 and Leu121-His135 (chymotryptic fragments). Trp125
      and Trp245 were identified as the sites of photoinsertion based on these residues
      not being detectable on sequencing, the lack of chymotryptic cleavage at these
      residues, and the decreased rate of trypsin digestion at nearby Lys243 and
      Lys127. Sequence analysis of [32P]8N3ATP and [32P]2N3ATP photolabeled peptides
      gave essentially the same peptide regions being photolabeled but at much lower
      efficiency, indicating that the effects of ATP on IDH activity are dependent on
      competition for the same site.

PMID- 8885830
TI  - Inactivation of human lung tryptase: evidence for a re-activatable tetrameric
      intermediate and active monomers.
AB  - Human lung tryptase (HLT), a trypsin-like serine proteinase stored as an active
      enzyme in association with heparin in mast cell granules, is released into the
      extracellular environment when mast cells are activated. Tryptases are unusual in
      that they form tetramers and bind heparin. As there are no known endogenous
      tryptase inhibitors, loss of heparin and dissociation of the active tetrameric
      enzyme to inactive monomers has been proposed as the mechanism of control.
      Activity and intrinsic fluorescence were used to measure the stabilization of HLT
      by NaCl, glycerol, and heparin. At physiological salt concentrations in the
      absence of heparin, activity decayed rapidly (t1/2 = 1-4 min at 37 degrees C) to
      an intermediate that could be immediately reactivated by heparin. But protein
      structural changes, as measured by intrinsic fluorescence, were much slower (t1/2
      = 16 min), indicating that the intermediate continued to exist as a tetramer that
      slowly changed to a monomer. HLT tetramers, either active or inactive, were
      stabilized by 2 M NaCl, 20% glycerol, and heparin. Maximum stabilization was
      obtained with approximately 1 mol of heparin per HLT subunit. Heparan sulfate
      also stabilized HLT activity and active HLT was bound to and recovered from
      cartilage. Subunits of the inactive intermediate appeared to be loosely
      associated as demonstrated by the rapid disappearance of the tetramer in gel
      filtration studies in 1 M NaCl (t1/2 = 1.8 min), but the tetramer was stable in
      lower ionic strength buffers containing heparin. Fluorescence anisotropy
      measurements in the absence of heparin were also consistent with a slow (t1/2 =
      22 min) transition from tetramer to monomer, and native polyacrylamide gel
      electrophoresis provided additional evidence for a tetrameric intermediate. HLT
      monomers isolated by gel filtration were minimally active in the presence of
      heparin. These data show that heparin-free HLT rapidly converts to an "inactive",
      loose tetrameric intermediate that can be reactivated with heparin or slowly
      dissociate to less active monomers and that tryptase released from mast cells is
      likely to remain active in association with heparin or other extracellular
      components. Thus, tryptase affinity for glycosaminoglycans and substrate
      specificity limitations are the primary factors controlling the proteolytic
      functions of these enzymes.

PMID- 8885831
TI  - Identification of the template-binding cleft of T7 RNA polymerase as the site for
      promoter binding by photochemical cross-linking with psoralen.
AB  - We describe a novel method of photo-cross-linking DNA-binding proteins to DNA
      employing psoralen as a tether. We apply this method for the interaction of T7
      RNA polymerase to its promoter. The crystallographic model of T7 RNA polymerase
      shows a cleft formed by the palm, thumb, and fingers domains. It was proposed
      that template DNA binds in the cleft. Here we directly and positively identify,
      in solution, the cleft as the seat of template binding. We photo-cross-linked a
      23 bp promoter DNA to T7 RNA polymerase. We then determined the masses of cross
      linked tryptic peptides by mass spectrometry and analyzed their amino acid
      composition. The cross-linked peptides were projected on the crystal structure of
      T7 RNA polymerase. The peptides nicely decorated the back, front, and side wall
      of the cleft. In a previous work [Sastry et al. (1993) Biochemistry 32, 5526
      5538] we used site-specific psoralen furan-side monoadducts for cross-linking
      DNAs to DNA-binding proteins. We cross-linked a single-stranded 12-mer
      oligonucleotide to T7 RNA polymerase. We isolated and purified a DNA cross-linked
      tryptic peptide. We then used mass spectrometry and amino acid composition
      analysis to identify the location of this peptide on the T7 RNA polymerase
      primary sequence. In the present work we have mapped this peptide on the 3-D
      structure of T7 RNA polymerase. This peptide maps in the fingers domain of the
      polymerase. On the basis of a comparison of the map positions of peptides that
      cross-linked to either promoter DNA or single-stranded oligo-DNA, we propose that
      different functional domains may be involved in binding of double-stranded
      promoter DNA and nonspecific single-stranded DNA. Whereas the cleft of the
      polymerase is the seat of double-stranded promoter binding, the fingers domain
      may be used by the polymerase to grab single-stranded DNA (or RNA) in a
      nonspecific manner. Alternatively, the single-stranded oligo binding site may be
      an RNA product-binding site during transcription. The photochemical techniques we
      have developed [Sastry et al. (1993) Biochemistry 32, 5526-5538; this work] can
      be applied to other DNA-protein complexes to map DNA-binding domains.

PMID- 8885832
TI  - Flavin reductase P: structure of a dimeric enzyme that reduces flavin.
AB  - We report the structure of an NADPH:FMN oxidoreductase (flavin reductase P) that
      is involved in bioluminescence by providing reduced FMN to luciferase. The 1.8 A
      crystal structure of flavin reductase P from Vibrio harveyi was solved by
      multiple isomorphous replacement and reveals that the enzyme is a unique dimer of
      interlocking subunits, with 9352 A2 of surface area buried in the dimer
      interface. Each subunit comprises two domains. The first domain consists of a
      four-stranded antiparallel beta-sheet flanked by helices on either side. The
      second domain reaches out from one subunit and embraces the other subunit and is
      responsible for interlocking the two subunits. Our structure explains why flavin
      reductase P is specific for FMN as cofactor. FMN is recognized and tightly bound
      by a network of 16 hydrogen bonds, while steric considerations prevent the
      binding of FAD. A flexible loop containing a Lys and an Arg could account for the
      NADPH specificity. The structure reveals information about several aspects of the
      catalytic mechanism. For example, we show that the first step in catalysis, which
      is hydride transfer from C4 of NADPH to cofactor FMN, involves addition to the re
      face of the FMN, probably at the N5 position. The limited accessibility of the
      FMN binding pocket and the extensive FMN-protein hydrogen bond network are
      consistent with the observed ping-pong bisubstrate--biproduct reaction kinetics.
      Finally, we propose a model for how flavin reductase P might shuttle electrons
      between NADPH and luciferase.

PMID- 8885833
TI  - Three-dimensional structure of meso-diaminopimelic acid dehydrogenase from
      Corynebacterium glutamicum.
AB  - Diaminopimelate dehydrogenase catalyzes the NADPH-dependent reduction of ammonia
      and L-2-amino-6-ketopimelate to form meso-diaminopimelate, the direct precursor
      of L-lysine in the bacterial lysine biosynthetic pathway. Since mammals lack this
      metabolic pathway inhibitors of enzymes in this pathway may be useful as
      antibiotics or herbicides. Diaminopimelate dehydrogenase catalyzes the only
      oxidative deamination of an amino acid of D configuration and must additionally
      distinguish between two chiral amino acid centers on the same symmetric
      substrate. The Corynebacterium glutamicum enzyme has been cloned, expressed in
      Escherichia coli, and purified to homogeneity using standard biochemical
      procedures [Reddy, S. G., Scapin, G., & Blanchard, J. S. (1996) Proteins:
      Structure, Funct. Genet. 25, 514-516]. The three-dimensional structure of the
      binary complex of diaminopimelate dehydrogenase with NADP+ has been solved using
      multiple isomorphous replacement procedures and noncrystallographic symmetry
      averaging. The resulting model has been refined against 2.2 A diffraction data to
      a conventional crystallographic R-factor of 17.0%. Diaminopimelate dehydrogenase
      is a homodimer of structurally not identical subunits. Each subunit is composed
      of three domains. The N-terminal domain contains a modified dinucleotide binding
      domain, or Rossman fold (six central beta-strands in a 213456 topology surrounded
      by five alpha-helices). The second domain contains two alpha-helices and three
      beta-strands. This domain is referred to as the dimerization domain, since it is
      involved in forming the monomer--monomer interface of the dimer. The third or C
      terminal domain is composed of six beta-strands and five alpha-helices. The
      relative position of the N- and C-terminal domain in the two monomers is
      different, defining an open and a closed conformation that may represent the
      enzyme's binding and active state, respectively. In both monomers the nucleotide
      is bound in an extended conformation across the C-terminal portion of the beta
      sheet of the Rossman fold, with its C4 facing the C-terminal domain. In the
      closed conformer two molecules of acetate have been refined in this region, and
      we postulate that they define the DAP binding site. The structure of
      diaminopimelate dehydrogenase shows interesting similarities to the structure of
      glutamate dehydrogenase [Baker, P. J., Britton, K. L., Rice, D. W., Rob, A., &
      Stillmann, T.J. (1992a) J. Mol. Biol. 228, 662-671] and leucine dehydrogenase
      [Baker, P.J., Turnbull, A.P., Sedelnikova, S.E., Stillman, T. J., & Rice, D. W.
      (1995) Structure 3, 693-705] and also resembles the structure of
      dihydrodipicolinate reductase [Scapin, G., Blanchard, J. S., & Sacchettini, J. C.
      (1995) Biochemistry 34, 3502-3512], the enzyme immediately preceding it in the
      diaminopimelic acid/lysine biosynthetic pathway.

PMID- 8885834
TI  - High-resolution solution structure of basic fibroblast growth factor determined
      by multidimensional heteronuclear magnetic resonance spectroscopy.
AB  - The high-resolution solution structure of recombinant human basic fibroblast
      growth factor (FGF-2), a protein of 17.2 kDa that exhibits a variety of functions
      related to cell growth and differentiation, has been determined using three
      dimensional heteronuclear NMR spectroscopy. A total of 30 structures were
      calculated by means of hybrid distance geometry--simulated annealing using a
      total of 2865 experimental NMR restraints, consisting of 2486 approximate
      inteproton distance restraints, 50 distance restraints for 25 backbone hydrogen
      bonds, and 329 torsion angle restraints. The atomic rms distribution about the
      mean coordinate positions for the 30 structures for residues 29-152 is 0.43 +/-
      0.03 A for the backbone atoms, 0.83 +/- 0.05 A for all atoms, and 0.51 +/- 0.04 A
      for all atoms excluding disordered side chains. The overall structure of FGF-2
      consists of 11 extended antiparallel beta-strands arranged in three groups of
      three or four strands connected by tight turns and loop regions creating a pseudo
      3-fold symmetry. Two strands from each group come together to form a beta-sheet
      barrel of six antiparallel beta-strands. A helix-like structure was observed for
      residues 131-136, which is part of the heparin binding site (residues 128-138).
      The discovery of the helix-like region in the primary heparin binding site
      instead of the beta-strand conformation described in the X-ray structures may
      have important implications in understanding the nature of heparin--FGF-2
      interactions. A total of seven tightly bound water molecules were found in the
      FGF-2 structure, two of which are located in the heparin binding site. The first
      28 N-terminal residues appear to be disordered, which is consistent with previous
      X-ray structures. A best fit superposition of the NMR structure of FGF-2 with the
      1.9 A resolution X-ray structure by Zhu et al. (1991) yields a backbone atomic
      rms difference of 0.94 A, indicative of a close similarity between the NMR and X
      ray structures.

PMID- 8885835
TI  - Origin of carbohydrate recognition specificity of human lysozyme revealed by
      affinity labeling.
AB  - In order to reveal the origin of carbohydrate recognition specificity of human
      lysozyme by clarifying the difference in the binding mode of ligands in the
      active site, the inactivation of human lysozyme by 2',3'-epoxypropyl beta
      glycoside derivatives of the disaccharides, N,N'-diacetylchitobiose [GlcNAc-beta
      (1-->4)-GlcNAc] and N-acetyllactosamine [Gal-beta-(1-->4)-GlcNAc], was
      investigated and the three-dimensional structures of the affinity-labeled enzymes
      were determined by X-ray crystallography at 1.7 A resolution. Under the
      conditions comprising 2.0 x 10(-3) M labeling reagent and 1.0 x 10(-5) M human
      lysozyme at pH 5.4, 37 degrees C, the reaction time required to reduce the lytic
      activity against Micrococcus luteus cells to 50% of its initial activity was
      lengthened by 3.7 times through the substitution of the nonreducing end sugar
      residue, GlcNAc to Gal. The refined structure of human lysozyme labeled by 2',3'
      epoxypropyl beta-glycoside derivatives of N,N'-diacetylchitobiose (HL/NAG-NAG-EPO
      complex) indicated that the interaction mode of the N,N'-diacetylchitobiose
      moiety in substites B and C in this study was essentially the same as in the case
      of the complex of human lysozyme with the free ligand. On the other hand, the
      hydrogen-bonding pattern and the stacking interaction at subsite B were
      remarkably different between the HL/NAG-NAG-EPO complex and human lysozyme
      labeled by the 2',3'-epoxypropyl beta-glycoside of N-acetyllactosamine (HL/GAL
      NAG-EPO complex). The reduced number of possible hydrogen bonds as well as the
      less favorable stacking between the side chain of Tyr63 in human lysozyme and the
      galactose residue in the HL/GAL-NAG-EPO complex reasonably explained the less
      efficient ability of the 2',3'-epoxypropyl beta-glycoside of N-acetyllactosamine
      as compared to that of N,N'-diacetylchitobiose as an affinity labeling reagent
      toward human lysozyme.

PMID- 8885836
TI  - Nicotine inhibits amyloid formation by the beta-peptide.
AB  - The 42-residues beta-(1-42) peptide is the major protein component of amyloid
      plaque cores in Alzheimer's disease. In aqueous solution at physiological pH, the
      synthetic beta-(1-42) peptide readily aggregates and precipitates as oligomeric
      beta-sheet structures, a process that occurs during amyloid formation in
      Alzheimer's disease. Using circular dichroism (CD) and ultraviolet spectroscopic
      techniques, we show that nicotine, a major component in cigarette smoke, inhibits
      amyloid formation by the beta-(1-42) peptide. The related compound cotinine, the
      major metabolite of nicotine in humans, also slows down amyloid formation, but to
      a lesser extent than nicotine. In contrast, control substances pyridine and N
      methylpyrrolidine accelerate the aggregation process. Nuclear magnetic resonance
      (NMR) studies demonstrate that nicotine binds to the 1-28 peptide region when
      folded in an alpha-helical conformation. On the basis of chemical shift data, the
      binding primarily involves the N-CH3 and 5'CH2 pyrrolidine moieties of nicotine
      and the histidine residues of the peptide. The binding is in fast exchange, as
      shown by single averaged NMR peaks and the lack of nuclear Overhauser enhancement
      data between nicotine and the peptide in two-dimensional NOESY spectra. A
      mechanism is proposed, whereby nicotine retards amyloidosis by preventing an
      alpha-helix-->beta-sheet conformational transformation that is important in the
      pathogenesis of Alzheimer's disease.

PMID- 8885837
TI  - Furilisin: a variant of subtilisin BPN' engineered for cleaving tribasic
      substrates.
AB  - The serine protease, subtilisin BPN', was engineered to cleave proteins after
      tribasic sequences in a manner that resembles the substrate specificity of furin,
      one of the mammalian subtilisin homologs that processes prohormones. As a
      starting point we used a double mutant of subtilisin BPN' (N62D/ G166D) that
      showed substantial preference for cleaving after sequences having consecutive
      dibasic residues (namely, at the P1 and P2 substrate positions) [Ballinger et al.
      (1995) Biochemistry 34, 13312-13319]. Additional specificity for basic residues
      was engineered at the P4 position by introducing subtilisin-to-furin
      substitutions at three hydrophobic residues that composed the S4 subsite (Y104,
      I107, and L126). Initial attempts to incorporate a Y104D or I107E mutation or the
      Y104D/I107E double mutation into the dibasic specific enzyme failed to generate
      the processed enzyme. The problem was traced to the inability of the mutant
      prosubtilisins to process themselves and fold correctly. Replacing the natural
      processing site sequence (AHAY) with a good furin substrate sequence (RHKR)
      resulted in expression of the triple subtilisin mutant (N62D/Y104D/G166D) we call
      "furilisin". Furilisin hydrolyzes synthetic tribasic substrates (succinyl-RAKR
      pNA or succinyl-KAKR-pNA) with high catalytic efficiency (kcat/K(m) > 3 x 10(5) M
      1 s-1) and discriminates in favor of Arg versus Ala at the P4 position by a
      factor of 360. The overall specificity change versus the wild-type enzyme was
      dramatic. For example, succinyl-RAKR-pNA was cleaved approximately 60000 times
      faster than succinyl-AAPF-pNA, a good substrate for wild-type subtilisin.
      Similarly, furilisin was inhibited (K1* = 29 nM) by a variant of the turkey
      ovomucoid third domain inhibitor that contained an engineered furin substrate
      site (RCKR decreases) [Lu et al. (1993) J. Biol. Chem. 268, 14583-14585] and not
      by one having a good wild-type subtilisin substrate sequence (ACTL decreases).
      Interestingly, the extreme changes in substrate specificity resulted from
      substantial synergy between the engineered subsites. These studies provide a
      basic example of how to manipulate substrate specificity in a modular fashion,
      thereby creating an engineered-enzyme that may be useful as a protein processing
      tool.

PMID- 8885838
TI  - A model of the iron responsive element RNA hairpin loop structure determined from
      NMR and thermodynamic data.
AB  - The iron responsive element (IRE) is a conserved RNA structure that is found in
      the 5' UTR of ferritin mRNA and in the 3' UTR of transferrin receptor mRNA. It is
      the binding site of the iron responsive protein (IRP), and the interaction is
      part of the regulation of cellular iron metabolism. The IRE six-nucleotide
      hairpin loop, 5'C1A2G3U4G5N6, is conserved in sequence, and mutations have shown
      that it is required for IRP binding. On the basis of the thermodynamic and NMR
      experiments utilized here, the IRE loop structure 5'C1A2G3U4G5C6, is described in
      detail. Measurements of loop stability show that it has 2.9 kcal/mol more free
      energy than predicted. NMR data suggest that there is hydrogen bonding between C1
      and G5 in a tertiary interaction across the loop. A model structure, produced by
      MC-SYM/energy minimization, illustrates the conformational flexibility of U4 and
      C6, which appear to exhibit considerable local motion in solution. NMR data
      indicate that the position of G3 is not well defined, leading to two families of
      loop structures.

PMID- 8885839
TI  - Solution structures of 5-fluorouracil-substituted DNA and RNA decamer duplexes.
AB  - The structures in solution of eight oligonucleotide duplexes each containing
      either zero, one, or two 5-fluorodeoxyuridine (FdUrd) or 5-fluorouridine (FUrd)
      nucleosides were determined by the combined use of NMR spectroscopy, restrained
      molecular dynamics, and full relaxation matrix refinement to determine how FdUrd
      and FUrd substitution affects the structure of duplex DNA and RNA and to
      establish whether structural differences due to FdUrd and FUrd substitution in
      nucleic acids may be responsible, in part, for the biological effects of the
      anticancer drug 5-fluorouracil (FUra). The nucleic acid directed effects of FUra
      include induction of single-strand breaks in duplex DNA and altered processing of
      pre-mRNA and rRNA. Four self-complementary oligodeoxyribonucleotide sequences
      were prepared and studied as duplexes in aqueous solution: (5' dGCGAAUUCGC)2, (5'
      dGCGAAUFCGC)2, (5' dGCGAAFUCGC)2, and (5' dGCGAAFFCGC)2. The corresponding
      oligoribonucleotide sequences (5' rGCGAAUUCGC)2, (5' rGCGAAUFCGC)2, (5'
      rGCGAAFUCGC)2, and (5' rGCGAAFFCGC)2 were also prepared and studied. The helical
      parameters for the structures of these eight duplexes were analyzed to determine
      how substitution of FdUrd and FUrd affects the three-dimensional structures of
      duplex DNA and RNA. FdUrd substitution affects the base roll angle at the site of
      FdUrd substitution, causing the helical axis of FdUrd-substituted DNA duplexes to
      be bent compared to the nonsubstituted duplex. A-FUrd base pairs show substantial
      RMS deviations from A-Urd base pairs in all three of the RNA duplexes substituted
      with FUrd. Bending of the helical axis due to FdUrd substitution may contribute
      to the occurrence of single-strand breaks in duplex DNA while the altered
      structures of A-FUrd base pairs may affect RNA-RNA and RNA-protein recognition.

PMID- 8885840
TI  - Site-directed mutagenesis, kinetic, and spectroscopic studies of the P-loop
      residues in a low molecular weight protein tyrosine phosphatase.
AB  - The structure of the specific phosphate binding loop (P-loop) of bovine protein
      tyrosine phosphatase (BPTP) is very similar to that present in high M(r) PTPases.
      Site-directed mutagenesis was used to explore the role of several conserved
      residues involved in forming the P-loop of BPTP. Thus, Ser-19 and Ser-43 were
      individually mutated to alanines, and Asn-15 was mutated to alanine and
      glutamine. The 1H NMR spectra of the mutants showed good conservation of global
      secondary structure when compared to wild-type enzyme. Kinetic measurements
      revealed that only S19A and N15A had substantially altered catalytic activities
      toward p-nitrophenyl phosphate at pH 5.0, with both mutants exhibiting Vmax
      values that were 0.25-0.33% of wild-type enzyme. Further kinetic analyses of the
      N15A and S19A mutants were performed using phosphomonoester substrates with
      varied phenolic leaving groups. For S19A, the slope of the correlation between
      Vmax and the substrate leaving group pKa was significantly altered, consistent
      with a change of the rate-determining step from dephosphorylation to
      phosphorylation. This was confirmed by partitioning experiments employing
      methanol as an alternative nucleophile in the dephosphorylation step. Thus,
      mutating Ser-19 to alanine reduced the efficiency of nucleophilic attack by Cys
      12. It is concluded that Ser-19 acts to facilitate the ionization and orientation
      of Cys-12 for optimal reaction as a nucleophile and as a leaving group. It also
      appears that Asn-15, Ser-19, His-72, and to a lesser extent Ser-43 serve
      structural functions that allow the active site to adopt an optimal geometry for
      phosphate binding. The Asn-15 to Ala mutation appears to disrupt the hydrogen
      bonding network, with an accompanying alteration of the geometry of the P-loop.
      These conclusions are also consistent with changes in the stability of the
      respective proteins, as measured by urea denaturation.

PMID- 8885841
TI  - Bis-methionine ligation to heme iron in mutants of cytochrome b562. 1.
      Spectroscopic and electrochemical characterization of the electronic properties.
AB  - We have generated mutants of cytochrome b562 in which the histidine ligand to the
      heme iron (His102) has been replaced by a methionine. The resulting proteins can
      have bis-methionine coordination to the heme iron, but the stability of this
      arrangement is dependent on oxidation state and solution pH. We have used
      optical, MCD, and EPR spectroscopies to study the nature of the heme coordination
      environment under a variety of conditions. Optical spectra of the reduced state
      of the single variant, H102M, are consistent with bis-methionine ligation. In its
      oxidized state, this protein is high-spin under all conditions studied, and the
      spectroscopic properties are consistent with only one of the methionine ligands
      being coordinated. We cannot identify what, if anything, provides the other axial
      ligand. A double variant, R98C/H102M (in which the heme is covalently attached to
      the protein through a c-type thioether linkage), is also bis-methionine
      coordinated in the ferrous state, but has significantly different properties in
      the oxidized state. With a pKa of 7.1 at 20 degrees C, the protein converts from
      a low-spin, 6-coordinate heme protein at low pH, to a high-spin species, similar
      to the high-spin species observed for the single variant. Our spectroscopic data
      prove that the low-spin species is bis-methionine coordinated. The reduction
      potential of this bis-methionine species has been measured using direct
      electrochemical techniques and is +440 mV at pH 4.8. The electrochemistry of
      these proteins is complicated by coupled coordination-state changes. Proof that
      the ferrous state is bis-methionine coordinated is provided by NMR results
      presented in the following paper.

PMID- 8885842
TI  - Bis-methionine ligation to heme iron in mutants of cytochrome b562. 2.
      Characterization by NMR of heme-ligand interactions.
AB  - Previous work has shown that, in variants of cytochrome b562 containing the H102M
      mutation, methionine residues provide both axial ligands to the heme iron. NMR
      spectroscopic studies of such bis-methionine-coordinated cytochrome have not
      previously been feasible, since the only other cytochrome with such a ligand
      arrangement, bacterioferritin, is too large to be studied by current NMR methods.
      The present work provides the first NMR characterization of 6-coordinate, bis
      methionine-ligated heme centers in both ferrous and ferric oxidation states. We
      have used one and two dimensional, homonuclear NMR spectroscopy to assign the
      proton resonances of the heme group and ligand side chains in the reduced,
      cytochrome b562 variants, H102M and covR98C/H102M. The latter protein has heme
      covalently attached to the protein, and our results prove that the covalent
      linkage is a c-type thioether bond formed between the cysteine at residue 98 and
      the heme 2-vinyl group. Spectra of the ferrous H102M variant are consistent with
      the presence of two species differing in the orientation of the heme in the
      protein. We have interpreted results from NOESY experiments on the ferrous
      covR98C/H102M protein in terms of the conformation of the two methionine side
      chains, and we present a model for the structure of the heme ligand arrangement.
      The Met7 side chain adopts an extended conformation almost identical to that
      observed in the wild type protein with R stereochemistry at the chiral sulfur
      ligand. The Met102 side chain has a different, buckled side chain conformation
      and has S stereochemistry at the chiral center. Our NMR derived model is
      consistent with the spectroscopic data presented in the previous paper. Studies
      on the ferric forms of these proteins confirm that the double variant at low pH
      has a "stable" bis-methionine ligation arrangement, but that it is a thermal
      mixture of species with differing spin states. No hyperfine coupled proton
      resonances can be identified in spectra of the high-spin forms of either of these
      proteins.

PMID- 8885843
TI  - Glutathione-dependent pathways of refolding of RNase T1 by oxidation and
      disulfide isomerization: catalysis by protein disulfide isomerase.
AB  - Protein folding, associated with oxidation and isomerization of disulfide bonds,
      was studied using reduced and denatured RNase T1 (rd-RNase T1) and mixed
      disulfide between glutathione and reduced RNase T1 (GS-RNase T1) as starting
      materials. Folding was initiated by addition of free glutathione (GSH + GSSG) and
      was monitored by electrospray mass spectrometry (ES-MS) time-course analysis.
      This permitted both the identification and quantitation of the population of
      intermediates present during the refolding process. Refolding experiments were
      performed in the presence of different absolute concentrations of glutathione
      species while keeping the redox potential fixed, in order to evaluate the effect
      of the glutathione concentration on the distribution of the refolding
      intermediates. All the analyses indicate a pathway of sequential reactions in the
      formation of native RNase T1 which occurs via the reiteration of two steps: (i)
      formation of a species containing both mixed disulfides with glutathione and free
      protein thiols, and (ii) formation of an intramolecular disulfide via thiol
      disulfide interchange reaction between them. Refolding of rd-RNase T1 and GS
      RNase T1 was also performed in the presence of protein disulfide isomerase (PDI).
      Addition of PDI led to a catalysis of each individual reaction of the entire
      process without altering the refolding pathway. Refolding reactions carried out
      at different absolute concentrations of glutathione proved that GSH and/or GSSG
      participate directly in the reaction catalyzed by PDI. On the basis of these
      experiments and previous results on the refolding of RNase A [Torella, C.,
      Ruoppolo, M., Marino, G., & Pucci, P. (1994) FEBS Lett. 352, 301-306], a
      hypothesis of a general pathway for folding of S--S containing proteins is
      proposed.

PMID- 8885845
TI  - Dynamic instability of microtubules assembled from microtubule-associated protein
      free tubulin: neither variability of growth and shortening rates nor "rescue"
      requires microtubule-associated proteins.
AB  - The growth and shortening of microtubules in dynamic instability is known to be
      modulated by microtubule-associated proteins (MAPs). A full understanding of the
      mechanism of dynamic instability requires that one distinguish which of its
      aspects are mediated by microtubule-associated proteins (even in small residual
      concentrations) and which are intrinsic properties of the tubulin lattice itself.
      This paper addresses two of those aspects: whether MAPs cause the rescue events
      of dynamic instability (i.e., the transitions from shortening to growth) and
      whether MAPs are responsible for the marked variability of the rates at which
      microtubules grow and shorten. Very pure tubulin was prepared by sequential
      chromatographies on phosphocellulose and DEAE-Sephadex. Analysis by
      electrophoresis and immunoblotting showed it to be essentially MAP-free; it
      contained fewer than one MAP molecule per 10000 tubulin dimers. When its dynamic
      instability was studied by video-DIC microscopy, rescues were found to occur at a
      mean frequency of one per 4 microns of shortening. Variability of rates of growth
      and shortening, which is observed on the length scale of a few micrometers, was
      not changed by removal of MAPs. Because the mean distance between bound MAP
      molecules was calculated to be greater than 14 microns in these experiments, it
      is concluded that they cannot cause either rescue or variability of rates.

PMID- 8885844
TI  - Structure and in vitro substrate specificity of the murine multidrug resistance
      associated protein.
AB  - MRP is a recently described ATP-binding cassette transporter that confers
      cellular resistance to natural product cytotoxic drugs. To examine the
      biochemical activity and cellular physiology of this transporter, we isolated the
      murine MRP homologue and analyzed its in vitro substrate specificity. Murine MRP
      transcript is widely expressed in tissues and encodes a protein of 1528 amino
      acids that is 88% identical to its human homologue. Hydropathy analysis indicated
      that murine and human MRP, the yeast cadmium resistance transporter and the
      sulfonylurea receptor share a conserved topology distinguished from P
      glycoprotein and the cystic fibrosis conductance regulator by an N-terminal
      hydrophobic region that contains several potential transmembrane domains. Drug
      uptake assays performed with membrane vesicles prepared from NIH3T3 cells
      transfected with a murine MRP expression vector revealed ATP-dependent transport
      for the natural product cytotoxic drugs daunorubicin and vincristine, as well as
      for the glutathione S-conjugates leukotriene C4 and azidophenacyl-S-glutathione.
      Drug transport was osmotically sensitive and saturable with regard to drug and
      ATP concentrations, with K(m) values of 19 microM, 19 microM, 26 nM, 17 microM,
      and 77 microM for daunorubicin, vincristine, leukotriene C4, APA-SG, and ATP,
      respectively. Consistent with broad substrate specificity, the drug glutathione
      conjugate APA-SG, oxidized glutathione, the LTD4 antagonist MK571, arsenate, and
      genistein were competitive inhibitors of daunorubicin transport, with Ki values
      of 32 microM, 25 microM, 1.9 microM, 108 microM, and 23 microM, respectively.
      This study demonstrates that the substrate specificity of murine MRP is quite
      broad and includes both the neutral or mildly cationic natural product cytotoxic
      drugs and the anionic products of glutathione conjugation. The widespread
      expression pattern of murine MRP in tissues, combined with its ability to
      transport both lipophilic xenobiotics and the products of phase II
      detoxification, indicates that it represents a widespread and versatile cellular
      defense mechanism.

PMID- 8885846
TI  - Disposition and biological activity of benzo[a]pyrene-7,8-dione. A genotoxic
      metabolite generated by dihydrodiol dehydrogenase.
AB  - A novel pathway of polycyclic aromatic hydrocarbon metabolism involves the
      oxidation of non-K-region trans-dihydrodiols to yield o-quinones, a reaction
      catalyzed by dihydrodiol dehydrogenase (DD). We have recently shown that in
      isolated rat hepatocytes (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo-[a] pyrene
      (BP-diol) was oxidized by this route to yield benzo [a] pyrene-7,8-dione (BPQ).
      We now report the disposition of BPQ and its mutagenic and genotoxic properties.
      Using [3H]BPQ it was found that 30% of the radioactivity was sequestered by rat
      hepatocytes into the cell pellet. Isolation of hepatocyte DNA provided evidence
      for a low level of covalent incorporation of BPQ into DNA (30 +/- 17 adducts/
      10(6) base pairs). Examination of the hepatocellular DNA by agarose gel
      electrophoresis following treatment with BPQ indicated that extensive
      fragmentation had occurred. DNA fragmentation was also observed when hepatocytes
      were treated with BP-diol and this effect was attenuated by indomethacin, a DD
      inhibitor. Hepatocytes treated with either BP-diol or BPQ were found to produce
      large quantities of superoxide anion radical (O2.-). The amount of O2.- generated
      by BP-diol was blocked by DD inhibitors. These data suggest that by diverting BP
      diol to BPQ reactive oxygen species (ROS) were generated which caused DNA
      fragmentation. The ability of BPQ to cause DNA strand scission was further
      studied using supercoiled phi X174 DNA. It was found that BPQ caused
      concentration-dependent (0.05-10 microM) strand scission in the presence of 1 mM
      NADPH (which promoted redox-cycling) provided CuCl2 (10 microM) was present.
      Complete destruction of the DNA was observed using 10 microM BPQ. This strand
      scission was prevented by catalase and hydroxyl radical scavengers but not by
      superoxide dismutase. These data indicate that ROS were responsible for the
      destruction of the DNA. Using 20 microM (+/-)-anti-7,8-dihydroxy-9,10-epoxy
      7,8,9,10-tetrahydrobenzo [a]pyrene [(+/-)-anti-BPDE] only single nicks in the DNA
      were observed indicating that BPQ was the more potent chemical nuclease. BPQ was
      also found to be a direct-acting mutagen in the Ames test using Salmonella
      typhimurium tester strains TA97a, TA98, TA100, TA102, and TA104, but was 10-5500
      fold less efficient as a mutagen than (+/-)-anti-BPDE. Our data indicate that DD
      suppresses the mutagenicity of (+/-)-anti-BPDE by producing BPQ, but in doing so
      a potent chemical nuclease is produced which causes extensive DNA fragmentation
      via the generation of ROS.

PMID- 8885848
TI  - Structure-based thermodynamic scale of alpha-helix propensities in amino acids.
AB  - A structural parameterization of the folding energetics has been used to predict
      the effect of single amino acid mutations at exposed locations in alpha-helices.
      The results have been used to derive a structure-based thermodynamic scale of
      alpha-helix propensities for amino acids. The structure-based thermodynamic
      analysis was performed for four different systems for which structural and
      experimental thermodynamic data are available: T4 lysozyme [Blaber et al (1994)
      J. Mol. Biol.235, 600-624], barnase [Horovitz et al. (1992) J.Mol.Biol.227,560
      568], a synthetic leucine zipper [O'Neil & Degrado (1990) Science 250, 646-651],
      and a synthetic peptide [Lyu et al. (1990) Science 250, 669-673]. These studies
      have permitted the optimization of the set of solvent-accessible surface areas
      (ASA) for all amino acids in the unfolded state. It is shown that a single set of
      structure/thermodynamic parameters accounts well for all the experimental data
      sets of helix propensities. For T4 lysozyme, the average value of the absolute
      difference between predicted and experimental delta G values is 0.09 kcal/mol,
      for barnase 0.14 kcal/mol, for the synthetic coiled-coil 0.11 kcal/mol, and for
      the synthetic peptide 0.08 kcal/mol. In addition, this approach predicts well the
      overall stability of the proteins and rationalizes the differences in alpha-helix
      propensities between amino acids. The excellent agreement observed between
      predicted and experimental delta G values for all amino acids validates the use
      of this structural parameterization in free energy calculations for folding or
      binding.

PMID- 8885847
TI  - Kinetics of electron and proton transfer during the reaction of wild type and
      helix VI mutants of cytochrome bo3 with oxygen.
AB  - Site-directed mutagenesis was used to investigate the mechanism of electron and
      proton transfer in the ubiquinol oxidase, cytochrome bo3, from Escherichia coli.
      The reaction between the fully reduced form of the enzyme and dioxygen was
      studied using the flow--flash method. After rapid mixing of CO-bound enzyme with
      an O2-containing solution, CO was photodissociated, and the subsequent electron-
      and proton-transfer reactions were measured spectrophotometrically, the latter
      using a pH-indicator dye. In the wild-type, pure bo3 enzyme, without bound
      quinones, we observed a single kinetic phase with a rate constant of about 2.4 x
      10(4) s-1, associated with formation of the ferry1 oxygen intermediate, followed
      by proton uptake from solution with a rate constant of about 1.2 x 10(4) s-1.
      Enzyme in which heme o instead of heme b was incorporated into the low-spin site
      displayed a slower ferry1 formation with a rate constant of about 3.6 x 10(3) s
      1. Upon replacement of the acidic residue glutamate 286 in helix VI of subunit I
      with a nonprotonatable residue, electron transfer was slightly accelerated, and
      proton uptake was impaired. Mutations of other residues in the vicinity of E286
      also resulted in a dramatic decrease of proton uptake, suggesting that the
      environment of this residue is important for efficient proton transfer. In the
      closely related cytochrome aa3 from P. denitrificans, the corresponding residue
      (E278) has been suggested to be part of a proton-transfer pathway [Iwata, S.,
      Ostermeier, C., Ludwig, B., & Michel, H. (1995) Nature 376, 660-669]. The results
      are discussed in terms of a model for electron-proton coupling during dioxygen
      reduction.

PMID- 8885849
TI  - Inhibition of HIV-1 Rev-RRE interaction by diphenylfuran derivatives.
AB  - The interactions between RNA structures, such as RRE in the HIV-1 genome, and
      proteins, such as Rev of HIV-1, are essential for efficient viral replication.
      Compounds that bind specifically to such RNAs and disrupt their protein complexes
      offer a novel mechanism for inhibition of replication of the virus. As a step in
      this approach, we have designed and characterized a series of synthetic
      diphenylfuran cations that selectively inhibit Rev binding to RRE. Fluorescence
      titrations and gel band-shift results indicate that the diphenylfurans bind to
      RRE and inhibit Rev complex formation in a structure-dependent manner. The
      derivative with the greatest affinity for RRE has an association constant of
      greater than 10(7) M-1 and inhibits formation of the Rev--RRE complex at
      concentrations below 1 microM. It binds to RRE considerably more strongly than it
      binds to simple RNA duplexes. Spectral changes and energy transfer results on
      complex formation suggest that the compound has a nonclassical intercalation
      binding mode. CD studies with modified RRE hairpins indicate that the active
      diphenylfurans bind at the structured internal loop of RRE and cause a
      conformational change. The most active diphenylfurans are tetracations that
      appear to bind to RRE by a threading intercalation mode and cause a
      conformational change in the RNA that is essential for inhibition of Rev complex
      formation with RRE.

PMID- 8885850
TI  - HIV-1 membrane fusion mechanism: structural studies of the interactions between
      biologically-active peptides from gp41.
AB  - Two synthetic peptides corresponding to sequences in HIV-1LAI gp41, (aa558-595)
      and T20 (aa 643-678), are strong inhibitors of HIV-1 viral fusion, having EC50
      values of 1 microgram/mL and 1 ng/mL, respectively. Previous work suggested that
      T21 forms a coiled-coil structure in PBS solution, while T20 is primarily
      nonhelical, and that the inhibitory action of these peptides occurs after the
      interaction between the viral gp120 protein and the cellular CD4 receptor [Wild,
      C.T., Shugars, D. C., Greenwell, T. K., McDanal, C. B., Matthews, T. J. (1994)
      Proc. Natl. Acad. Sci. U.S.A. 91, 9770 and references therein]. The current study
      uses sedimentation equilibrium (SE), circular dichroism (CD), and viral-fusion
      assays to quantitatively investigate peptide structure and peptide-peptide
      interactions. SE analyses of T21 (1-100 microM) indicate that the peptide self
      associates via a monomer/dimer/tetramer equilibrium; in addition, T20 is
      monomeric in the range of 1-10 microM and exhibits a complicated monomer/tetramer
      equilibrium between 20 and 100 microM. Singular value decomposition analyses of
      the CD spectra of T21 and T20 indicate that the helical content of these peptides
      in PBS solution is 90% and 20%, respectively. A structural interaction between
      the two peptides is detected by CD at several concentration ratios of T20:T21.
      These experiments emphasize that T20 interacts specifically with the tetrameric
      form of T21. Truncated forms of T20 also exhibit structural interactions with T21
      at varying concentration ratios. The ability of T20 and the truncated peptides to
      interact structurally with tetrameric T21 correlates with antiviral activity.
      Implications of these findings are discussed in terms of proposed mechanisms of
      membrane fusion inhibition and the structural changes which occur in gp41 during
      membrane fusion.

PMID- 8885851
TI  - Chest 1996. World Congress. San Francisco, California, October 27-31, 1996.
      Abstracts.

PMID- 8885852
TI  - 69th Scientific Sessions of the American Heart Association. New Orleans,
      Louisiana, November 10-13, 1996. Abstracts.

PMID- 8885853
TI  - Soft tissue sarcomas.
AB  - Soft tissue sarcomas are relatively rare tumors with an annual incidence of 5000
      to 6000 in the United States. The primary therapy is surgical resection with an
      adequate margin of normal tissue. For patients at high risk local control is
      improved with postoperative adjuvant radiation. Local recurrence rates vary
      depending on the anatomic site. In extremity lesions one third of patients will
      have locally recurrent disease with a median disease-free interval of 18 months.
      Treatment results for extremity local recurrence may approach those for primary
      disease. Isolated pulmonary metastases may be resected with 20% to 30% 3-year
      survival rates. Patients with sarcomas in other sites present similar but more
      difficult problems in terms of local control and management of disseminated
      disease. Patients with unresectable pulmonary metastases or extrapulmonary
      metastatic sarcoma have a uniformly poor prognosis and are best treated with
      systemic chemotherapy.

PMID- 8885854
TI  - Do severity measures explain differences in length of hospital stay? The case of
      hip fracture.
AB  - OBJECTIVE: To examine whether judgments about hospital length of stay (LOS) vary
      depending on the measure used to adjust for severity differences. DATA
      SOURCES/STUDY SETTING: Data on admissions to 80 hospitals nationwide in the 1992
      MedisGroups Comparative Database. STUDY DESIGN: For each of 14 severity measures,
      LOS was regressed on patient age/sex, DRG, and severity score. Regressions were
      performed on trimmed and untrimmed data. R-squared was used to evaluate model
      performance. For each severity measure for each hospital, we calculated the
      expected LOS and the z-score, a measure of the deviation of observed from
      expected LOS. We ranked hospitals by z-scores. DATA EXTRACTION: All patients
      admitted for initial surgical repair of a hip fracture, defined by DRG,
      diagnosis, and procedure codes. PRINCIPAL FINDINGS: The 5,664 patients had a mean
      (s.d.) LOS of 11.9 (8.9) days. Cross-validated R-squared values from the
      multivariable regressions (trimmed data) ranged from 0.041 (Comorbidity Index) to
      0.165 (APR-DRGs). Using untrimmed data, observed average LOS for hospitals ranged
      from 7.6 to 23.9 days. The 14 severity measures showed excellent agreement in
      ranking hospitals based on z-scores. No severity measure explained the
      differences between hospitals with the shortest and longest LOS. CONCLUSIONS:
      Hospitals differed widely in their mean LOS for hip fracture patients, and
      severity adjustment did little to explain these differences.

PMID- 8885855
TI  - Inpatient stays for patients diagnosed with severe psychiatric disorders and
      substance abuse.
AB  - OBJECTIVE: To empirically determine if a substance abuse comorbidity is related
      to longer inpatient stays for patients diagnosed with schizophrenia and affective
      psychoses. STUDY DESIGN: A cross-sectional analysis of patients in three states:
      Maryland, California, and Arizona. Using multivariate techniques, we control for
      the effects of patient severity, insurance, and hospital characteristics on
      length of stay. DATA COLLECTION: We used a patient-level and state-specific
      hospital discharge database merged with hospital characteristics from the
      American Hospital Association. PRINCIPAL FINDINGS: The conventional wisdom is
      that patients with a substance abuse comorbidity have longer inpatient stays than
      similar patients without a substance abuse comorbidity. We did not observe this
      trend. We found wide variation in length of stay by state and patients' health
      insurance. In some cases, length of stay was statistically shorter for patients
      with a substance abuse comorbidity. CONCLUSIONS: Our research demonstrates that a
      substance abuse comorbidity does not necessarily equate to longer inpatient stays
      and that previous studies may overstate the impact of substance abuse on
      inpatient care utilization. In addition, we find that a relationship between
      substance abuse and length of stay may not be generalizable across states,
      diagnoses, hospitals, and/or insurance types. Future studies of the impact of
      substance abuse on inpatient stays need to control for these important
      covariates.

PMID- 8885856
TI  - Determinants of ambulatory mental health services use for school-age children and
      adolescents.
AB  - OBJECTIVE: To analyze a comprehensive multivariate model of the use of mental
      health-related ambulatory care services by children ages 6-17. STUDY SETTING: The
      1987 National Medical Expenditure Survey, a national probability sample of the
      U.S. civilian noninstitutionalized population. STUDY DESIGN: A cross-sectional
      survey of a national probability sample of the U.S. population. Key independent
      variables include person-level mental health status, health care coverage, family
      income, and use of mental health services by other family members. DATA
      COLLECTION: Four in-person interviews were conducted during 1987 using structured
      questionnaires. A designated family respondent was used to answer questions for
      other family members, including children. PRINCIPAL FINDINGS: Children with poor
      mental health in high-income families were more than three times as likely to
      have a mental health-related visit than children with poor mental health in low
      income families. The number of mental health-related visits and the likelihood of
      seeing a mental health specialist also increased along with family income. Mental
      health use by other family members was strongly associated with use. CONCLUSIONS:
      The results from this study provide strong evidence that the socioeconomic status
      of children is an important factor in explaining unmet need for mental health
      services.

PMID- 8885857
TI  - Rural and urban differences in physician resource use for low-risk obstetrics.
AB  - OBJECTIVE: To explore the hypothesis that rural obstetricians (OBs) and family
      physicians (FPs) utilized fewer resources during the care of the low-risk women
      who initially booked with them than did their urban counterparts of the same
      specialties. DATA SOURCES/STUDY DESIGN: A stratified random sample of Washington
      state rural and urban OBs and FPs was selected during 1989. A participation rate
      of 89 percent yielded 209 participating physicians. The prenatal and intrapartum
      medical records of a random sample of the low-risk patients who initiated care
      with the sampled providers during a one-year period were abstracted in detail and
      analyzed with the physician as the unit of analysis. Complete data for 1,683
      patients were collected. Resource use elements (e.g., urine culture) were
      combined by standardizing them with average charge data so that aggregate
      resource use could be analyzed. Intraspecialty comparisons for resource use by
      category and overall were performed. FINDINGS/CONCLUSIONS: Results show that
      rural physicians use fewer overall resources in caring for nonreferred low-risk
      booking obstetric patients than do their urban colleagues. Resource use unit
      expenditures showed the hypothesized pattern for both specialties for total,
      intrapartum, and prenatal care with the exception of FPs for prenatal care.
      Approximately 80 percent of the resource units used by each physician type were
      related to hospital care. No differences were shown in patterns of care for most
      clinically important aspects of care (e.g., cesarean delivery rates), and no
      evidence suggested that outcomes differed. The overall differences were due to
      specific components of care (e.g., fewer intrapartum hospital days and less
      epidural anesthesia).

PMID- 8885858
TI  - Evaluating the use of the appropriateness method in the Agency for Health Care
      Policy and Research Clinical Practice Guideline Development process.
AB  - OBJECTIVE: To assess the feasibility of the appropriateness method in the Agency
      for Health Care Policy and Research (AHCPR) Clinical Practice Guideline
      Development process, and to compare the results of the appropriateness method
      with those obtained using evidence tables and an informal consensus method.
      SETTING: AHCPR Low Back Problems Clinical Practice Guideline. DESIGN: Two
      different group process methods with the same panel of experts were used in
      observational comparison of results of and satisfaction with guideline
      development. DATA COLLECTION: Practice guideline statements were created for
      topics using the conventional AHCPR method; then six months later new guideline
      statements for four topics were created using the appropriateness method.
      Panelist satisfaction with each process and resulting set of guideline statements
      was assessed. PRINCIPAL FINDINGS: Results of the appropriateness method for TENS,
      discography, and traction showed no disagreement among panel members and no
      appropriate indications for their use in the patient scenarios considered. These
      results are qualitatively similar to the guideline statements produced using
      evidence tables and informal consensus. Clinical practice guideline statements
      about electro-diagnostics created from appropriateness ratings were much more
      clinically specific than those created using evidence tables and informal
      consensus. Neither informal consensus building nor the appropriateness method was
      clearly preferred by a majority of panelists. CONCLUSIONS: It is feasible to use
      the appropriateness method in the AHCPR Clinical Practice Guideline Development
      process, and in some instances it produces more clinically specific guideline
      statements than does informal consensus.

PMID- 8885859
TI  - Functional impairment trajectories among persons with HIV disease: a hierarchical
      linear models approach.
AB  - OBJECTIVE: This study investigates the level, time course, and stability of
      functional impairment in a population of persons with symptomatic HIV disease,
      and illustrates the application of hierarchical linear modeling (HLM) to
      trajectories of functional status in unbalanced longitudinal data. STUDY
      POPULATION: We utilized longitudinal interview data on a demographically diverse
      cohort of 246 individuals participating in New Jersey's Medicaid waiver program
      for persons with AIDS or symptomatic HIV disease, with a mean of nine repeated
      observations per individual. MEASURES AND STATISTICAL METHODS: Impairment in
      ability to perform 16 activities of daily living (ADL) and instrumental
      activities of daily living (IADL) was assessed at monthly intervals. To achieve
      unbiased, efficient estimation of the level and within-individual rate of change
      of functional status utilizing all observations for each individual, hierarchical
      linear models were used. Time slopes were compared to those from a single-level
      model estimated on the pooled observations. Stability of functional status within
      individuals was also evaluated. PRINCIPAL FINDINGS: A single-level pooled model
      showed no significant time trend in functional impairment, while the multilevel
      models did indicate such a trend. In the final HLM model, functional impairment
      was estimated to increase at a rate of .32 tasks per month. Female gender was
      associated with impairment in an additional 1.88 tasks and AIDS diagnosis with an
      additional 1.35 tasks. There was substantial variability within individuals over
      time, most of which was not explained by time trend. CONCLUSIONS: The multilevel
      models indicated a significant month-to-month worsening of functional status that
      was masked in the single-level model by between-person variation. Impairment was
      found to increase over time, but followed a variable and episodic course rather
      than a steady or consistent decline. Women appeared to experience special
      problems in performing ADL and IADL tasks. RELEVANCE/IMPACT: Results demonstrate
      the need for flexible and responsive systems for authorizing and managing in-home
      services for persons with HIV disease, systems that can respond to frequent
      changes in the functional status and level of care needs of these individuals.
      They suggest further attention to special care needs that may be experienced by
      women with HIV disease. They illustrate that hierarchical linear modeling can be
      an important tool in understanding change in functional status over time,
      providing a multilevel model that disaggregates within-individual and between
      individual variation in functional status. This approach can be generalized to a
      wide variety of problems in health services research in which outcomes are
      observed over time with unbalanced longitudinal data.

PMID- 8885860
TI  - Medicaid-funded home care for the frail elderly and disabled: evaluating the cost
      savings and outcomes of a service delivery reform.
AB  - OBJECTIVES: In response to rising demand and increased costs for home care
      services for frail elderly and disabled Medicaid clients, New York City
      implemented cluster care, a shared-aide model of home care. Our objective: to
      evaluate the effects of cluster care on home care hours and costs, client
      functioning, depressive symptoms, and satisfaction. DATA SOURCES: Client
      interviews, conducted prior to implementation and again 16 months later; Medicaid
      claims records; home attendant payroll files; and vendor agency records. STUDY
      DESIGN: The study employed a pretest/posttest design, comparing 229 clients at
      the first seven demonstration sites to 175 clients at four comparison sites
      before and after cluster care implementation. Regression methods were used to
      analyze pre and post-intervention data. PRINCIPAL FINDINGS: Cluster care reduced
      costs by about 10 percent. Most savings occurred among the more vulnerable
      clients (those with five or more ADL/IADL limitations). Clients at cluster care
      sites who started out with fewer than five limitations appeared to decline
      somewhat more slowly than similarly impaired clients at comparison sites, while
      those with more than five ADL/IADLs tended to decline more rapidly. This
      difference was small-less than one limitation per year. Cluster care is
      associated with a significant decline in satisfaction but appears unrelated to
      depressive symptoms. CONCLUSIONS: Cluster care appears benign for home care
      clients with fewer limitations. For the more vulnerable, we recommend
      experimentation with low-cost interventions that might augment service and
      improve outcomes without reverting to traditional one-on-one care.

PMID- 8885861
TI  - Improving care and constraining costs: evaluating New York City's cluster care
      demonstration.

PMID- 8885862
TI  - MHC class I-restricted CTL responses to exogenous antigens.

PMID- 8885863
TI  - Immune activation by bacterial DNA: a new genetic code.

PMID- 8885864
TI  - Triggering of natural killer cells by the costimulatory molecule CD80 (B7-1)
AB  - NK cell-mediated cytotoxicity is influenced by triggering as well as inhibitory
      signals. The identification of inhibitory signals provided by MHC class I
      molecules has recently attracted significant attention. Much less is known about
      putative triggering signals. Using purified populations of mouse NK cells, we
      demonstrate that the CD80 (B7-1) gene product functions as a triggering signal
      for NK cell-mediated cytotoxicity. The strength of this response is such that it
      overrides the protection mediated by MHC class I molecules. Triggering of mouse
      NK cells by B7-1 occurred even in the absence of CD28 and could not be blocked by
      either anti-CD28 or anti-CTLA-4 antibodies. NK cells may thus, at least in part,
      use receptors other than CD28 and CTLA-4 in their interaction with B7-1.
      Furthermore, we demonstrate that bone marrow-derived macrophages and dendritic
      cells are highly susceptible to lysis by autologous NK cells.

PMID- 8885865
TI  - The SCID but not the RAG-2 gene product is required for S mu-S epsilon heavy
      chain class switching.
AB  - We have investigated the capacity of precursor B cells from normal (BDF1) and
      V(D)J recombinase-deficient (RAG-27) or defective (SCID) mice to be induced by a
      CD40-specific monoclonal antibody and IL-4 to epsilon H chain gene transcription
      and to S mu-S epsilon switch recombination. In differentiating precursor B cells
      from all three strains of mice, the development of similar numbers of CD19+,
      CD23+, CD40+, and MHC class II+ expressing B lineage cells and similar levels of
      epsilon H chain gene transcription were induced. Efficient S mu-S epsilon
      switching occurred in normal and RAG-2-deficient, but not in SCID, precursor B
      cells. Thus, the transcription of the epsilon H chain is independent of the RAG-2
      and the SCID gene product, while the S mu-S epsilon switch recombination requires
      the SCID gene-encoded DNA-dependent protein kinase, but not the RAG-2 protein.

PMID- 8885866
TI  - Defect in rearrangement of the most 5' TCR-J alpha following targeted deletion of
      T early alpha (TEA): implications for TCR alpha locus accessibility.
AB  - To address the role of the TEA germline transcription, which initiates upstream
      of the TCR-J alpha S, in the regulation of TCR-J alpha locus accessibility, we
      created a mouse in which this region has been removed by homologous
      recombination. Normal development of T alpha beta cells and the expression of
      other TCR alpha germline transcripts in TEA-/- mice ruled out an exclusive role
      for TEA in the overall accessibility of the J alpha cluster. However, the
      rearrangement of the most 5' J alpha (J alpha 61 to J alpha 53) was severely
      impaired, indicating that TEA may control the DNA accessibility of a particular J
      alpha window. Moreover, the relative usage of every J alpha segment was affected.
      These results are consistent with TEA acting as a "rearrangement-focusing"
      element, targeting the primary waves of V alpha-J alpha recombination to the most
      5' J alpha S in an ongoing TCR-J alpha rearrangement model.

PMID- 8885867
TI  - The alpha beta T cell receptor can replace the gamma delta receptor in the
      development of gamma delta lineage cells.
AB  - In peripheral lymphoid tissues of TCR transgenic mice that express the nominal
      antigen (HY peptide plus H-2Db MHC) recognized by the transgenic TCR, there exist
      unusual CD4-CD8- and CD4-CD8low cells bearing the transgenic TCR. Here we show
      that, unlike TCR alpha beta T cells that are generated in the absence of nominal
      antigen, these unusual cells do not express endogenous TCR alpha genes, have
      maintained the TCR delta locus on both chromosomes, and can coexpress TCR alpha
      beta and TCR gamma delta chains on the cell surface. The latter is also true for
      CD4-CD8-, HSA+ TCR alpha beta + thymocytes in male and female TCR transgenic
      mice. The number of TCR alpha beta and TCR gamma delta coexpressing cells is
      increased in pre-TCR-deficient mice. The data indicate that the TCR alpha beta
      can replace the TCR gamma delta in the development of gamma delta lineage cells
      and that the pre-TCR interferes with the generation of gamma delta-expressing
      cells.

PMID- 8885868
TI  - Protein kinase C mu (PKC mu) associates with the B cell antigen receptor complex
      and regulates lymphocyte signaling.
AB  - We have identified a Ser/Thr kinase associated with the B cell receptor (BCR)
      complex as protein kinase C mu (PKC mu). PKC mu activity is up-regulated after
      cross-linking the BCR and CD19 on B cells, and PKC mu co-precipitates with Syk
      and phospholipase C-gamma 1/2 (PLC gamma 1/2). In vitro phosphorylation of fusion
      proteins showed that both Syk and PLC gamma 1 are potential substrates of PKC mu
      in vivo. Analysis of mutants of the chicken B cell line DT40 deficient in either
      Syk, Lyn, Btk, or PLC gamma 2 revealed that BCR-induced activation of PKC mu,
      like activation of PLC gamma 2, requires Syk and is partially regulated by Btk,
      but is Lyn independent. PKC mu can down-regulate the ability of Syk to
      phosphorylate PLC gamma 1 in vitro. Thus, PKC mu may function in a negative
      feedback loop regulating BCR-initiated signaling cascades.

PMID- 8885869
TI  - Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells
      in IRF-1-/- mice.
AB  - The TAP1 and LMP2 genes are central for class I MHC function and share a common
      promoter. Here, we analyze the molecular mechanism of IFN gamma up-regulation of
      TAP1 and LMP2. In vivo footprinting indicates IFN gamma up-regulates protein-DNA
      contacts at an IRF-E that is essential for the up-regulation of TAP1 and LMP2 by
      IFN gamma. Gel shift analysis indicates that this site binds IRF-1. The
      expression of TAP1 and LMP2 are both greatly reduced in IRF-1-deficient mice.
      Surface class I MHC as well as CD8+ T cells are reduced in IRF-1-/- mice. The
      role of IRF-1 in the regulation of TAP1 and LMP2 suggests a mechanism for the
      antiviral properties of IRF-1 and the unexpected deficiency of CD8+ T cells
      observed in IRF-1-/- mice.

PMID- 8885870
TI  - An interleukin-2 signal relieves BSAP (Pax5)-mediated repression of the
      immunoglobulin J chain gene.
AB  - Cytokine regulation of B cell development was analyzed using interleukin-2 (IL-2)
      induced transcription of the J chain gene as a model system. A nuclear target of
      the IL-2 signal was identified as the Pax5 transcription factor, BSAP, which
      recognizes a negative regulatory motif in the J chain promoter. Functional assays
      showed that BSAP mediates the silencing of the J chain gene during the early
      stages of B cell development, but repression is relieved during the antigen
      driven stages in a concentration-dependent manner by an IL-2-induced down
      regulation of BSAP RNA expression. At the low levels present in J chain
      expressing plasma cells, BSAP repression could be overridden by positive-acting
      factors binding to down-stream J chain promoter elements. Overexpression of BSAP
      in these cells reversed the positive regulation and inhibited J chain gene
      transcription. Thus, IL-2 regulation of BSAP concentration may provide a
      mechanism for controlling both repressor and activator functions of BSAP during a
      B cell immune response.

PMID- 8885871
TI  - A dominant role for mast cell Fc receptors in the Arthus reaction.
AB  - Antibody-antigen complexes are central to the inflammatory response and are
      implicated in the development of such diverse diseases as systemic lupus
      erythematosis, rheumatoid arthritis, immune glomerulonephritis, and vasculitis.
      We recently demonstrated that experimental immune complex-mediated injury in
      mice, as modeled by the cutaneous Arthus reaction, requires receptors for the Fc
      portion of the antibody and is unaffected by deficiencies in complement
      components. However, the responsible cell type(s) and Fc receptor(s) were not
      known. We now demonstrate by differential reconstitution in vivo that Fc gamma
      RIII on mast cells is necessary for this inflammatory response. We propose a
      general model of antibody-mediated diseases as an immunopathologic spectrum whose
      specific manifestations are determined by the Fc receptor and cell type engaged.

PMID- 8885872
TI  - Inhibition of sexual behavior in male mice infected with Taenia crassiceps
      cysticerci.
AB  - Prominent estrogenization and deandrogenization ensue in male mice as a
      consequence of experimental intraperitoneal infection with Taenia crassiceps
      cysticerci. The impact of these endocrine changes upon sexual behavior was
      explored in a group of infected Balb/c male mice at weekly intervals for 15 wk
      and compared with the behavior of otherwise paired, nonparasitized male mice.
      Mounting, intromission, and ejaculation responses markedly declined as infection
      progressed. Six weeks after infection, none of the infected mice displayed
      ejaculation, the number of mounts and intromissions gradually decreased, and
      their latencies increased, until, by the 13th wk, none of the parasitized mice
      showed any sexual response toward female mice. Fifteen weeks after infection, the
      number of metacestodes per host increased to a couple of thousand, the mean serum
      estradiol level was approximately 50 times higher than the normal value, and
      testosterone fell to 5% of its normal level. To fully assess that the inhibition
      of sexual behavior resulted from the decrease in testosterone levels, a group of
      8-wk-infected mice received testosterone, and complete restoration of their
      sexual behavior was observed. Inhibition of masculine sexual behavior during the
      infection period is the result of hormonal changes, estradiol being ineffective
      in maintaining copulation.

PMID- 8885873
TI  - Acyl-CoA transferase activities in homogenates of Fasciola hepatica adults.
AB  - Succinyl-CoA is an intermediate in the formation of the fermentation product,
      propionate, by Fasciola hepatica adults. Acyl-CoA transferase activities are
      present in crude homogenates of Fasciola, which could account for the synthesis
      of succinyl-CoA from succinate by the transfer of CoA from either propionyl-CoA
      or acetyl-CoA. No transferase activity was apparent from 2-methylbutyryl-CoA or 2
      methylvaleryl-CoA as was previously reported for the nematode, Ascaris suum. Heat
      denaturation experiments indicate that all of the Fasciola transferase activities
      may result from a single protein.

PMID- 8885874
TI  - On the distribution and abundance of eel parasites in Nova Scotia: local versus
      regional patterns.
AB  - Site-to-site variation in macroparasite species distribution and richness was
      observed in eels (Anguilla rostrata) among 7 sites in the Timber Lake drainage
      system, Nova Scotia. There was a positive relationship between maximum local
      species distribution, as measured by maximum prevalence at a site, and regional
      distribution, as measured by the number of sites in which a parasite was found
      within the watershed and among 28 sites across Nova Scotia. Species richness
      increased with spatial scale. However, the species richness of host-specific
      parasites approached a maximum at the spatial scale of the watershed, whereas
      that of generalist parasites continued to increase with increasing scale. The
      near-peak in species richness of eel specialists at the watershed level suggests
      that in a functional sense for these parasites it is the spatial scale of the
      watershed that serves as a species pool from which local species richness is
      derived.

PMID- 8885875
TI  - Comparison of Leptorhynchoides thecatus (Acanthocephala) recruitment into green
      sunfish and largemouth bass populations.
AB  - The degree to which host suitability is a reflection of host community structure
      in generalist parasites was studied experimentally in the common fish
      acanthocephalan Leptorhynchoides thecatus. Previous study has shown that green
      sunfish (Lepomis cyanellus) are required, and largemouth bass (Micropterus
      salmoides) are suitable (but not required) hosts, where they occur sympatrically
      in natural communities. The present study examined populations of L. cyanellus
      and M. salmoides held separately in mesocosms and exposed to L. thecatus
      cystacanths via laboratory-infected Hyalella azteca (Amphipoda). Recruitment,
      maturation, and transmission of worms were examined over a 17-wk period and
      compared between fish species. Infections with L. thecatus were found as early as
      2 wk after the introduction of cystacanth-infected amphipods, and by week 11
      fishes of both species harbored gravid worms. Immature worms were observed in
      both host species by week 17 and were presumed to be a result of natural egg
      production and release resulting in infections of amphipods and the subsequent
      reinfection of fish. No significant difference in the prevalence, abundance,
      percentage of worms gravid, or time of parasite maturation was found between host
      populations. Results indicate that the different roles played by these host
      species in the maintenance of L. thecatus supra-populations in natural systems
      are not due to intrinsic factors but rather to differences in host autecology and
      community structure.

PMID- 8885876
TI  - Interspecific differences between small mammals as hosts of immature Dermacentor
      variabilis (Acari: Ixodidae) and a model for detection of high risk areas of
      Rocky Mountain spotted fever.
AB  - Fourteen species of small mammals were captured from July 1990 through August
      1991 in Tennessee, from which 1,217 immature Dermacentor variabilis and 1 Ixodes
      dentatus were collected. Mammal species were given scores of importance (TS) as
      hosts to immature D. variabilis based on mean intensity and prevalence. The rice
      rat ranked the highest, with a TS = 5, followed by the golden mouse TS = 4, white
      footed mouse TS = 3, pine vole TS = 2, cotton rat TS = 1, with the Norway rat,
      house mouse, and short-tailed shrew all having a TS = 0. Assigning a TS allows a
      quantitative method for differentiating and ranking small mammals as hosts for
      immature D. variabilis. Relative abundance of a species can also be important in
      determining D. variabilis populations, even with a low TS. The potential of Rocky
      Mountain spotted fever (RMSFP) to occur in an area was estimated using the total
      score of small mammal hosts in an area and multiplying the relative abundance of
      important host species. The RMSFP of a site, based only upon small mammal species
      composition and relative abundance of important host species, was an accurate
      estimate of adult D. variabilis infesting raccoons and opossums at that trap site
      (P < or = 0.001). A RMSFP of 1.61 is needed to produce an estimated 252 adults
      per ha (RMSF threshold) at 98% survival of engorged immature ticks (P < 0.001).

PMID- 8885877
TI  - Morphological and molecular characterization of Giardia isolated from the straw
      necked ibis (Threskiornis spinicollis) in Western Australia.
AB  - Following the first report of avian Giardia infection in Australia, isolates of
      the parasite recovered from naturally infected straw-necked ibis (Theskiornis
      spinicollis) were characterized using median body morphology, scanning electron
      microscopy, multilocus enzyme electrophoresis, random amplified polymorphic DNA
      (RAPD), and small subunit ribosomal RNA (SSU-rRNA) analyses. Results were
      compared with Giardia from other birds and mammals, and the extent of genetic
      diversity between a range of ibis isolates collected in Western Australia was
      determined. The ibis isolates of Giardia were genetically relatively homogeneous,
      which is in contrast to the extensive genetic heterogeneity often displayed by
      mammalian Giardia isolates. Morphologically, Giardia from ibis were similar to
      Giardia ardeae although they differed genetically and by the fact that the ibis
      isolates could not be established in in vitro culture. Sequence data of the DNA
      coding for the SSU-rRNA found a 96% homology between the ibis isolates from
      Western Australia and G. ardeae, suggesting that they represent distinct strains
      of the same species. In contrast, the ibis isolates were genetically and
      morphologically very different than Giardia duodenalis and Giardia muris from
      mammals.

PMID- 8885879
TI  - Killing of Toxoplasma gondii oocysts by irradiation and protective immunity
      induced by vaccination with irradiated oocysts.
AB  - Toxoplasma gondii oocysts are highly resistant to environmental influences. To
      study the effect of alpha-irradiation on the viability of T. gondii oocysts, 1
      million sporulated oocysts of the VEG strain were irradiated to absorbed doses of
      0.10, 0.15, 0.20, 0.25, 0.30, 0.40, or 0.50 kGy at 5 C with a 137Cs gamma
      irradiation source. Treated oocysts were bioassayed for viable T. gondii in mice.
      Viable T. gondii was not found in brains of mice 2 mo after oral inoculation with
      oocysts irradiated at levels > or = 0.25 kGy. Therefore, alpha-irradiation is an
      effective means of killing T. gondii oocysts. Mice inoculated orally with oocysts
      irradiated at 0.20 and 0.40 kGy were partially protected when challenged orally
      with lethal doses of nonirradiated oocysts.

PMID- 8885878
TI  - Production of IL-1 alpha and IL-1 beta by human skin equivalents parasitized by
      Sarcoptes scabiei.
AB  - Human skin equivalents (HSEs) were used as a model to investigate interleukin
      (IL)-1 alpha and IL-1 beta secretions by keratinocytes stimulated by Sarcoptes
      scabiei (SS). SS mites burrowed into the stratum corneum when placed on the
      surface of cultured HSEs. Mites lived for 14 days. Mites and mite products
      induced cells in the HSEs to secrete IL-1 alpha and IL-1 beta within 16 hr.
      Scabies mites induced production of greater amounts of IL-1 alpha than IL-1 beta.
      Hepatocyte growth factor in the culture medium at 3 and 30 ng/ml upregulated the
      secretions of both IL-1 alpha and IL-1 beta by mite-infested skin equivalents,
      whereas 10 ng/ml of IL-6 upregulated production of only IL-1 beta. Therefore,
      these cytokines were important immunomodulating factors influencing keratinocyte
      secretion of IL-1 alpha and IL-1 beta in vitro. The results of this study provide
      the first evidence that keratinocytes (possibly fibroblasts) in the skin produce
      these cytokines in response to scabies mites or other ectoparasitic arthropods.
      Because IL-1 alpha and IL-1 beta are potent inducers of inflammation and
      keratinocytes are among the first effector cells to encounter scabies mites and
      their products, these cells may be key initiators of the inflammatory/immune
      reaction to scabies.

PMID- 8885880
TI  - Experimental Babesia microti infection in golden hamsters: immunoglobulin G
      response and recovery from severe hemolytic anemia.
AB  - We described the parasitemia, hematologic changes, and immunity developed by
      golden hamsters during 8 wk of infection with Babesia microti following
      experimental inoculation. All 8 hamsters used in this study were readily
      infected. Animals attained peak parasitemias asynchronously but within a 2-wk
      period. Most of the animals reached their peak parasitemia by 4 wk
      postinoculation, attaining a mean +/- SD of 21.9 +/- 9.4% infected erythrocytes
      (range = 20-35%). Red blood cell count, packed cell volume, and hemoglobin level
      were used to monitor the course of the hemolytic anemia experienced by infected
      hamsters. All 3 measures corresponded inversely to the parasitemia; significant
      hematologic changes (P = 0.0001) were observed during the 8 wk of monitoring.
      Although all hamsters suffered from severe hemolytic anemia, they also recovered
      within the same period. Golden hamsters developed a detectable anti-B. microti
      IgG response by 2 wk postinoculation. Individual animals typically attained peak
      antibody levels (> or = 1:8, 192) 1 wk after the peak parasitemia. Hamsters
      retained a high IgG titer (> or = 1:4,096), although parasitemias fell
      dramatically, fluctuating thereafter at low levels (< 5%).

PMID- 8885881
TI  - Primary and secondary Toxoplasma gondii infection in normal and feline
      immunodeficiency virus-infected cats.
AB  - Normal and asymptomatic feline immunodeficiency virus (FIV)-infected adult cats
      were inoculated orally with Toxoplasma gondii tissue cysts to assess differences
      in clinical disease, T. gondii serologic test results, hematologic results, and
      oocyst shedding. There was no difference between FIV-naive and FIV-infected cats
      in terms of clinical illness and duration of oocyst shedding following primary
      exposure. Both groups of cats developed significant decreases in neutrophil
      counts following primary inoculation with T. gondii; FIV-infected cats that were
      neutropenic prior to inoculation with T. gondii developed the most profound
      decreases in neutrophil numbers. Both FIV-naive and FIV-infected cats became
      lymphopenic during acute T. gondii infection; however, only FIV-naive cats
      developed lymphocytosis in the recovery stage. FIV-infected cats had lower total
      CD4+ and higher total CD8+ T-lymphocyte counts than FIV-naive cats prior to
      inoculation with T. gondii, but changes in these lymphocyte subsets were similar
      between groups of cats during the first several weeks after inoculation.
      Toxoplasma gondii infection had neither an ameliorating nor enhancing effect on T
      lymphocyte subset abnormalities in FIV-infected cats during acute or chronic
      infection. Both groups of cats developed comparable levels of T. gondii-specific
      IgM and IgG antibodies and T. gondii antigen-specific lymphocyte blastogenic
      responses following primary inoculation. Both groups of cats were fed T. gondii
      tissue cysts 66 wk following primary exposure and both groups were solidly immune
      as evidenced by a lack of oocyst shedding and only minor changes in IgM but not
      IgG antibodies.

PMID- 8885882
TI  - Fate of Schistosoma mansoni in Biomphalaria obstructa.
AB  - Histological sections of Biomphalaria obstructa snails exposed to miracidia of
      Schistosoma mansoni revealed that although viable sporocysts occurred in 6 of 9
      snails at 3 days postexposure (DPE), all were dead by 7 DPE. Most dead sporocysts
      appeared to have degenerated slowly rather than having been killed by host
      hemocytic responses, which were minimal. What appeared to be amorphous remnants
      of sporocysts could still be found at 31 DPE. In 7 of 10 snails infected
      simultaneously with S. mansoni and Echinostoma paraensei, viable schistosome
      sporocysts occurred at 7 DPE, possibly as a result of interference with hemocyte
      function by the echinostome. However, in snails exposed to E. paraensei 48 hr
      prior to S. mansoni, no viable schistosome sporocysts were found at 7 DPE.
      Biomphalaria obstructa may be only temporarily susceptible to infection with E.
      paraensei, rediae of which undergo degeneration, hemocyte-mediated destruction,
      or both by 7-9 DPE.

PMID- 8885883
TI  - Cryptosporidium parvum is not transmissible to fish, amphibians, or reptiles.
AB  - A recent report suggested that an isolate of Cryptosporidium parvum had
      established infections in fish, amphibians, and reptiles and raises concern that
      animals other than mammals might be a potential source of waterborne
      Cryptosporidium oocysts. To test this possibility, viable C. parvum oocysts,
      infectious for neonatal BALB/c mice, were delivered by gastric intubation to
      bluegill sunfish, poison-dart frogs, African clawed frogs, bearded dragon
      lizards, and corn snakes. Histological sections of the stomach, jejunum, ileum,
      and cloaca prepared from tissues collected on days 7 and 14 postinoculation (PI)
      were negative for Cryptosporidium developmental stages. However, inoculum-derived
      oocysts were detectable by fluorescein-labeled monoclonal antibody in feces of
      inoculated animals from day 1 to day 12 PI in fish and frogs, and up to day 14 PI
      in lizards. Snakes did not defecate for 14 days PI. Impression smears taken at
      necropsy on days 7 and 14 PI revealed C. parvum oocysts in the lumen of the
      cloaca of 2 fish and 1 lizard on day 7 PI only. Because tissue stages of the
      pathogen were not found, it appears that C. parvum was not heterologously
      transmitted to lower vertebrates. Under certain circumstances, however, such as
      after the ingestion of C. parvum-infected prey, lower vertebrates may disseminate
      C. parvum oocysts in the environment.

PMID- 8885884
TI  - Experimental transfer of Ascaris suum from donor pigs to helminth naive pigs.
AB  - The difficulties in experimentally establishing patent intestinal infections with
      the pig large roundworm Ascaris suum make transfer of adult or larval stages a
      potentially important method of inducing this infection. Adult worms and 10-day
      old larvae were transferred by stomach tube to untreated pigs and pigs treated
      with the gastric acid pump inhibitor omeprazole, as well as surgically directly
      into the small intestine of pigs. Transfer of adult worms resulted in patent
      infections with comparable worm survival rates in all 3 recipient groups but with
      a nonsignificant decrease in egg production after transfer to untreated pigs.
      Thus, it is possible with oral transfer of adult worms to achieve infections with
      more or less known numbers and sexes of the parasites, as well as producing
      patent infections in hosts that have never experienced a hepato-tracheal
      migration. Whereas the orally transferred 10-day-old L3/L4 larvae did not
      establish well, surgical transfer of larvae to helminth-naive recipient pigs
      resulted in high recovery rates 1 wk after transfer in 3 out of 5 pigs.

PMID- 8885885
TI  - Simplified methods for obtaining purified oocysts from mice and for growing
      Cryptosporidium parvum in vitro.
AB  - Seven- to 8-day-old Arc/Swiss mice were infected with 100,000-120,000
      Cryptosporidium parvum oocysts. At 8 days postinfection (PI) the jejunum, ileum,
      cecum, colon, and rectum were removed. Using a simple extraction procedure and
      purification by Ficoll gradient centrifugation, we rountinely obtained between 3
      6 million and up to 15 million purified oocysts per mouse. For in vitro
      cultivation, purified oocysts were pretreated in a low pH (2.5-3) 0.5% trypsin
      solution for 20 min, resuspended in supplemented RPMI-1640 containing glucose 0.1
      g (5.55 mM), sodium bicarbonate 0.3 g, bovine bile 0.02 g, folic acid 25
      micrograms, 4-aminobenzoic acid 100 micrograms, calcium pantothenate 50
      micrograms, ascorbic acid 875 micrograms, penicillin G 10,000 U and streptomycin
      0.01 g per 100 ml, and 1% fetal bovine serum (pH 7.4 before filtration), and used
      to inoculate confluent monolayers of the human adenocarcinoma cell line HCT-8.
      Incubation was in a candle jar at 37 C. We tested numerous supplements to RPMI
      1640, different pHs, and atmospheric conditions and found the parameters
      described above produced the greatest parasite numbers in vitro. We obtained
      significantly superior growth of C. parvum grown in HCT-8 cells using the
      conditions described above than in culture conditions described previously.

PMID- 8885886
TI  - Dependence of growth, metabolic expression, and pathogenicity of Naegleria
      fowleri on exogenous porphyrins.
AB  - The pathogenicity of the free-living amoeba Naegleria fowleri is modulated by the
      composition of the medium used for cultivation. The constituents that determine
      the level of pathogenicity of N. fowleri, however, have not been definitively
      established. The present study examined the effects of selected porphyrins on N.
      fowleri amoebae. The iron-containing porphyrins, hemin or hematin, or the iron
      free porphyrin, protoporphyrin IX, were effective in supporting growth of N.
      fowleri in Cline medium lacking serum. Iron-binding proteins, including
      hemoglobin, could not satisfy the growth requirement of the amoebae for exogenous
      porphyrin. Expression of biological functions including azocaseinase activity,
      agglutination, mobility, complement susceptibility, and virulence were altered by
      the composition of the growth medium. Amoebae grown in Cline medium supplemented
      with either hemin or protoporphyrin IX displayed greater mobility and were more
      resistant to lysis by complement than those grown in Nelson medium. Similarly,
      amoebae grown in Cline medium supplemented with either hemin or protoporphyrin IX
      were more pathogenic for B6C3F1 mice than those grown in Nelson medium. The
      addition of protoporphyrin IX to Nelson medium resulted in a modest increase in
      mobility, resistance to complement lysis and virulence when compared to N.
      fowleri amoebae grown in Nelson medium without added porphyrin.

PMID- 8885887
TI  - In vitro destruction of nerve cell cultures by Acanthamoeba spp.: a transmission
      and scanning electron microscopy study.
AB  - Trophozoites of 4 species of Acanthamoeba were cytopathic for cultured rat B103
      neuroblastoma cells. Cytopathogenicity was evaluated by a chromium release assay
      and by transmission and scanning electron microscopy. Acanthamoeba culbertsoni,
      Acanthamoeba castellanii, and Acanthamoeba polyphaga destroyed B103 target cells
      at 37 C as evidenced by the release of radiolabel. Acanthamoeba astronyxis did
      not produce cytopathology at 37 C but destroyed nerve cells at 25 C. Transmission
      and scanning electron microscopy of cocultures maintained at different time
      periods revealed that all species of Acanthamoeba exhibited long cylindrical
      structures, termed digipodia, which made contact with target cells. Following
      this effector cell-target cell contact, membrane blebbing on the nerve cells was
      observed. These events were followed either by lysis of target nerve cells or
      ingestion of the target cells via food-cups and their subsequent channeling into
      intracytoplasmic food vacuoles. Use of the TUNEL (TdT-mediated dUTP nick end
      labeling) technique indicated that approximately 40% of B103 cells incubated with
      A. culbertsoni, 20% of B103 cells cocultured with A. castellanii or with A.
      polyphaga, and less than 1% of B103 cells incubated with A. astronyxis at 37 C
      were apoptotic after 24 hr of coculture. Studies using electron microscopy
      indicated that Acanthamoeba trophozoites destroyed nerve cells both by cytolysis
      and by ingestion of whole nerve cells via food-cups.

PMID- 8885888
TI  - Re-evaluation of Mazamastrongylus dagestanica (Trichostrongylidae) with
      descriptions of the synlophe, genital cone, and other structural characters.
AB  - The synlophe of specimens of Mazamastrongylus dagestanica was characterized
      laterally and ventrally by a strongly tapering system of ridges in the cervical
      zone. This pattern, including the prominent system of "hood" ridges adjacent to
      the excretory pore and the absence of continuous subdorsal and subventral ridges
      is considered typical for the genus Mazamastrongylus. The synlophe of males and
      females was largely identical, with 37-41 ridges at the midbody. The lateral
      synlophe, where 2 pairs of ridges converge and terminate on the lateralmost ridge
      anterior to the cervical papillae appears unique for M. dagestanica and indicates
      that species-specific patterns may be recognized for Mazamastrongylus spp. Among
      male specimens, a bilobed ventral membrane, distinct from the simple and unpaired
      membrane, which envelops the "O" papillae, extends posterolaterally from the
      genital cone. It had not been described in detail previously and was also found
      in M. odocoilei and M. pursglovei. Characters of the bursa, genital cone, and
      spicules are consistent with placement of M. dagestanica in Mazamastrongylus;
      referral of this species to Spiculopteragia cannot be supported.

PMID- 8885889
TI  - Koronacantha mexicana n. gen., n. sp. (Acanthocephala: Illiosentidae) from marine
      fishes in Chamela Bay, Jalisco, Mexico.
AB  - A new species and genus of Acanthocephala is described based on specimens found
      in the intestine of Anisotremus interruptus (Gill, 1862), Haemulon sexfasciatum
      Gill, 1863, Haemulon scudderi Gill, 1863, Pomadasys leuciscus (Gunther, 1864),
      and Eugerres sp. Jordan and Evermann, 1927, from the marine waters of Chamela
      Bay, Jalisco, Mexico. Koronacantha mexicana n. sp. is characterized by having an
      elongate proboscis with a heavy cuticle, cuticular body spines, and 8 cement
      glands, indicating that it should be assigned to the Illiosentidae Golvan, 1960.
      The genus Koronacantha n. gen. can be distinguished from other members of the
      family by the possession of (1) a row of heavy, strongly recurved proboscis hooks
      in the shape of an inverted apostrophe with roots that are simple but exaggerated
      in size and a small hook blade, occurring just anterior to a posteriormost
      comblike group of 4 or 5 small, close-set hooks, (2) cerebral ganglion near
      middle of proboscis receptacle, and (3) paired sensory papillae at mid-neck.

PMID- 8885890
TI  - Systematic resolution of Crossobothrium Linton, 1889, and taxonomic information
      on four species allocated to that genus.
AB  - The systematic status of the tetraphyllidean genus Crossobothrium is resolved.
      The description of the type species Crossobothrium laciniatum is emended to
      include new information from light and electron microscopy. Orygmatobothrium
      dohrnii is transferred to Crossobothrium and its description is emended.
      Crossobothrium dohrnii n. comb. differs from C. laciniatum in the morphology of
      large microtriches on the distal bothridial surface, the presence of irregular
      papillose projections on the distal bothridial surface, the possession of
      irregular, incomplete loculi on the bothridial margin morphology, and exhibiting
      oblong testes. The genital pore position of C. dohrnii also differs from C.
      laciniatum. Species of Crossobothrium differ from species in other sampled
      tetraphyllidean genera in apical sucker tegumentary surface morphology. The 2
      species differ from species in all tetraphyllidean genera in possessing a field
      of deep longitudinal muscles and a greater number of follicles in the vitelline
      field at the level of the ovary. Two species formerly allocated to
      Crossobothrium, Phyllobothrium filiforme, and Phyllobothrium triacis, are
      transferred to Paraorygmatobothrium, and their descriptions are emended. Three
      other species previously allocated to Crossobothrium, namely Orygmatobothrium
      angustum, Phyllobothrium squali, and Tetrabothrius longicolle, are considered
      incertae sedis. As a taxonomic entity, Crossobothrium has suffered from a case of
      mistaken identity with tetraphyllidean species consistent in morphology with the
      genus Paraorygmatobothrium.

PMID- 8885891
TI  - Bothriocephalus pearsei n. sp. (Cestoda: Pseudophyllidea) from cenote fishes of
      the Yucatan Peninsula, Mexico.
AB  - The cestode Bothriocephalus pearsei n. sp. is described from the intestine of the
      cichlid Cichlasoma urophthalmus (Gunther) from cenote (= sinkhole) Zaci near
      Valladolid, Yucatan, Mexico. The pimelodid catfish Rhamdia guatemalensis Gunther,
      which also harbored conspecific cestodes, seems to represent accidental or
      postcyclic host of B. pearsei. The new species differs from congeners mainly by
      the morphology of the scolex, which is clavate, with the maximum width in its
      middle part, has a distinct but weakly muscular apical disc; 2 short and wide
      bothria distinctly demarcated in their anterior part, becoming indistinct
      posteriorly in the middle part of the scolex, and 2 elongate, lateral grooves. In
      addition to the scolex morphology, the new species can be differentiated from
      Bothriocephalus species parasitizing North American freshwater fishes as follows:
      B. claviceps (Goeze, 1782), a specific parasite of eels in the Holarctic, B.
      cuspidatus Cooper, 1917, occurring mostly in perciform fishes in North America,
      B. musculosus Baer, 1937 found in the cichlid Cichlasoma biocellata (Regan) (= C.
      octofasciatum (Regan)), and B. texomensis Self, 1954, described from Hiodon
      alosoides (Rafinesque), are much larger, with strobilae consisting of relatively
      short and very wide proglottids versus small-sized strobila (length 26-32 mm)
      composed of about 70 proglottids, which are only slightly wider than they are
      long (ratio 1:1-3), rectangular, or even longer than wide in the last proglottids
      in B. pearsei. Bothriocephalus formosus Mueller and Van Cleave, 1932, described
      from Percopsis omiscomaycus (Walbaum) in the USA, can be distinguished from B.
      pearsei, besides the different shape of the scolex, by the distribution of
      vitelline follicles, which are not separated into 2 lateral fields and are
      present along the midline of proglottids in the former species. Bothriocephalus
      acheilognathi, a widely distributed parasite of fishes of many families, in
      particular of cyprinids, distinctly differs from B. pearsei by its arrow- or
      heart-shaped scolex, larger strobila, and vitelline follicles scattered along the
      midline of proglottids in the former taxon. Bothriocephalus pearsei is also
      typified by its fish hosts, which are both of Neotropical origin, and by its
      geographical distribution limited to isolated deep-lying cenotes of inferior
      Yucatan.

PMID- 8885892
TI  - A multivariate analysis of morphometric characters of Heterorhabditis species
      (Nemata: Heterorhabditidae) and the role of morphometrics in the taxonomy of
      species of the genus.
AB  - A multivariate analysis on the morphometrics of 7 Heterorhabditis species was
      conducted to review the status of the traditional morphometric characterization
      methods for differentiating species of these nematodes. Results from this study
      showed consistency in the selection of morphometric characters for discriminating
      among males and infective juveniles of Heterorhabditis species. For the males,
      testis reflexion (TREF) and total length (LENGTH) were the variables that
      contributed most in the discrimination among the different species, and for the
      infective juveniles, tail length (TAILL) and total length (LENGTH) were the
      variables that contributed most. Therefore, we consider that these morphometric
      characters are useful and reliable, and that they should be used for the
      identification of Heterorhabditis species/isolates.

PMID- 8885894
TI  - Ultrastructure and development of the body cuticle of Oesophagostomum dentatum
      (Strongylida, Nematoda).
AB  - The ultrastructure, development, and morphogenesis of the body cuticle of adult
      and juvenile Oesophagostomum dentatum (Strongylida, Nematoda) were investigated
      by light microscopy, scanning electron microscopy, and transmission electron
      microscopy. The cuticle of the first 3 juvenile stages consists of a trilaminate
      epicuticle, an amorphous layer, and a radially striated layer. In the last
      juvenile stage and the adult worm, the radially striated layer is replaced by a
      fibrous layer with 3 sublayers of giant fibers and a basal amorphous layer. The
      new forming cuticle of the 3rd juvenile stage exhibits the epicuticle and
      amorphous material and, at a later time, the epicuticle and the radially striated
      layer; finally, amorphous material appears between these layers. Our finding of a
      structural change in the cuticular morphology between the 3rd and 4th juvenile
      stage harmonizes with earlier reports about the Strongylida. Such a change occurs
      at different ontogenetic stages or seems to be missing in other nematodes.
      Morphogenetic events such as the formation of the radial striation layer from
      amorphous precursor material agrees with previous observations on strongylids.

PMID- 8885893
TI  - Effects of verapamil on acute murine Chagas' disease.
AB  - Continuous administration of verapamil significantly reduced the mortality rate
      of acute murine Trypanosoma cruzi infection (P < 0.05). The mechanistic basis for
      these observations was investigated. Verapamil and other calcium-channel blockers
      did not inhibit the growth of epimastigotes in culture. Furthermore, verapamil
      did not inhibit the intracellular growth of amastigotes in endothelial cells as
      determined by the uptake of 3H-uracil. There were no significant differences in
      parasitemia between infected mice that were untreated and those treated with
      verapamil. Twenty days postinfection infected, untreated mice had a parasitemia
      of 5.8 x 10(6) trypomastigotes/ml (SD +/- 2 x 10(6)), whereas infected, verapamil
      treated mice had a parasitemia of 2.2 x 10(6) trypomastigotes/ml (SD +/- 0.5 x
      10(6)). There was no significant difference in mortality between mice
      administered verapamil only for the initial 10 days of murine infection compared
      to those treated continuously. A 3-day delay in the initiation of verapamil
      administration reduced the mortality rate, but a 10-day delay did not.
      Propranolol (beta-adrenergic blocker), prazosin (alpha 1-adrenergic blocker), and
      diltiazem (another calcium-channel blocker) reduced the mortality but not
      significantly (P = 0.07). In biochemical studies of the beta- adrenergic signal
      transduction complex, we determined that verapamil and propranolol reversed the
      infection-associated decrease in myocardial beta- adrenergic adenylyl cyclase
      activity. In contrast, complementary western blot analysis revealed no
      significant changes in the G-proteins of the beta- adrenergic receptor complex 45
      days postinfection. Therefore, these results suggest that the basis of
      verapamil's influence on the early critical period of infection is multifactorial
      and independent of a direct trypanocidal effect.

PMID- 8885895
TI  - The first record of a member of the genus Hepatozoon in the eastern barred
      bandicoot (Perameles gunnii) in Tasmania.
AB  - Of 220 wild Eastern Barred Bandicoots (Perameles gunnii) captured in two
      locations in Tasmania, Australia, 55 (25%) had a detectable parasitaemia with
      gametocytes of the protozoan genus Hepatozoon in blood films. Blood films were
      stained with Leishman stain and acridine orange O. Gamonts were commonly found as
      intracellular forms and occasionally observed as extracellular forms in
      peripheral erythrocytes. This is the first record of a member of the genus
      Hepatozoon in any temperate bandicoot and additionally appears to be the first
      record of this protozoan genus in any native marsupial species of Tasmania.

PMID- 8885896
TI  - The probability of a marine gastropod being infected by a trematode.
AB  - Sentinel snails were employed to determine the likelihood of an estuarine snail
      becoming infected with a trematode under natural conditions. In summers of 1991
      and 1993, Ilyanassa obsoleta (Mollusca: Gastropoda) (n = 1,400) were collected
      from a saltmarsh in Lewes, Delaware, where parasite prevalence was low, and
      screened for infections. Putatively uninfected snails were individually marked
      and released onto the nearby Cape Henlopen sandflat where prevalence of
      trematodes among native snails is very high (approximately 80%). Most sentinels
      were free in the field for 1-5 mo and 186 were ultimately recovered. The overall
      estimate of probability of infection is 1.6%. The snail lives for many years and
      this low probability of becoming infected indicates that high prevalence of
      trematodes in this host is brought about not by rapid colonization, but by slow
      accumulation over time.

PMID- 8885897
TI  - Helminths from three treefrogs Hyla arenicolor, Hyla wrightorum, and Pseudacris
      triseriata (Hylidae) from Arizona.
AB  - The gastrointestinal tracts, lungs, and urinary bladders of 3 species of
      treefrogs from Arizona were examined for helminths. Hyla arenicolor (n = 30) and
      Hyla wrightorum (n = 53) were infected by Cylindrotaenia americana, Cosmocercella
      haberi, and larvae of Physaloptera sp.; Pseudacris triseriata (n = 20) harbored
      Falcaustra catesbeianae. The highest prevalence (33%) and greatest mean intensity
      (112.2) was recorded for Cosmocercella haberi in H. arenicolor. The helminth
      fauna of these treefrogs is depauperate and consists of different species than
      those of other Arizona amphibians.

PMID- 8885898
TI  - Re-migration of fifth-stage juvenile Dirofilaria immitis into pulmonary arteries
      after subcutaneous transplantation in dogs, cats, and rabbits.
AB  - An assessment was made of the capacity for re-migration of the 5th-stage juvenile
      canine heartworm, Dirofilaria immitis. Live, 5th-stage juvenile worms recovered
      from the pulmonary arteries of infected dogs were transplanted into the
      subcutaneous tissue of uninfected dogs, cats, and rabbits. A mean of 45%, 61%,
      and 18% of the transplanted worms were recovered from the pulmonary arteries of
      dogs, cats, and rabbits, respectively, 1 and 3 mo later. The 5th-stage juvenile
      worms thus have the ability to re-migrate through tissue into the pulmonary
      arteries of the host.

PMID- 8885899
TI  - Surface ultrastructure of the cercaria of Neodiplostomum seoulense (Trematoda:
      Neodiplostomidae).
AB  - The surface ultrastructure of Neodiplostomum seoulense cercariae was studied by
      scanning electron microscopy. The cercarial body was cylindrical and its tail
      bifurcated. Short tegumental spines, with a broad base and single pointed tip,
      were dense anteriorly but sparse posteriorly on the lateral margins of the body.
      The acetabulum had stout spikelike spines, centripetally oriented on the inner
      surface. Sensory papillae, each with a short cilium, were concentrated around the
      oral sucker; they could be tangoreceptors or chemoreceptors, or both. Many
      sensory papillae, each with a long cilium, were observed on the tail; these might
      be rheo- or tangoreceptors. It is suggested that the sensory papillae of N.
      seoulense cercariae provide for attachment and penetration into the skin of
      tadpoles, which are the second intermediate host.

PMID- 8885900
TI  - Developmental study of Taenia mustelae in the intermediate and definitive hosts,
      with a note on the life cycle of T. mustelae in Hokkaido, Japan.
AB  - The gray red-backed vole Clethrionomys rufocanus bedfordiae and laboratory mice
      were fed eggs of Taenia mustelae via a stomach tube. Fully developed metacestodes
      were recovered from the voles fed the eggs at 25 days postinfection; voles were
      considered to be more suitable intermediate hosts for T. mustelae than laboratory
      mice. The prepatent period for the metacestodes from voles was shorter (16 days)
      in the mink than previously reported. A field survey was performed on hepatic
      cestodes of small mammals in Hokkaido, Japan in August 1993. We found T. mustelae
      metacestodes from C. rufocanus bedfordiae, representing a new host record.

PMID- 8885901
TI  - Experimental Toxoplasma gondii infection leading to fatal enteritis in reindeer
      (Rangifer tarandus).
AB  - Two, 50-60-kg yearling reindeer (Rangifer tarandus) were inoculated
      intraruminally with 5,000 (reindeer 1) or 50,000 (reindeer 2) oocysts of the ME
      49 strain of Toxoplasma gondii. Both reindeer became ill day 4 postinoculation
      (p.i.). Reindeer 2 died because of acute enteritis day 9 p.i. Histologically,
      extensive necrosis and destruction of the intestinal mucosa were seen. Numerous
      T. gondii organisms were demonstrated immunohistochemically. Reindeer 1 was
      treated with sulfatrimethoprim for 2 days from day 9, recovered by day 16 p.i.,
      and remained clinically normal until the last day of observation (day 707 p.i.).
      It developed high antibody titers to T. gondii between days 7 and 14 p.i.

PMID- 8885902
TI  - Observations on the free-living adult stage of Gordius dimorphus (Nematomorpha:
      Gordioidea).
AB  - A total of 119 adult hairworms, Gordius dimorphus, was collected on 2 occasions
      from a small mountain stream in New Zealand's South Island. Size dimorphism
      between male and female worms was much greater than previously reported. The
      average sizes of worms of either sex found in mixed-sex groups were no different
      from those of worms occurring either alone or in single-sex groups. In a sample
      taken in spring, the sex ratio was female biased, whereas in a sample from early
      summer the sex ratio was strongly male biased. A greater proportion of males was
      found in mixed-sex groups in early summer than in spring. Although laboratory
      experiments are needed, from the little evidence currently available it would
      appear that hairworms form mating groups more or less at random.

PMID- 8885903
TI  - Trichinella britovi from Japan.
AB  - Although parasites of the genus Trichinella have been collected from wild animals
      in Japan, they have never been studied at species level. Muscle larvae of
      Trichinella collected from a black bear (Ursus thibetanus japonicus) and from a
      raccoon dog (Nyctereutes procyonoides viverrinus) in Japan have been identified
      as Trichinella britovi by random amplified polymorphic DNA analysis. The presence
      of T. britovi in Japan shows that this parasite has a wide distribution in the
      Palaearctic region, from western Europe to eastern Asia, and that the isotherm -6
      C in January could be considered its northern border.

PMID- 8885904
TI  - Filariae of raccoons from southeast Georgia.
AB  - The prevalence of filariae in wild raccoons trapped in southeast Georgia was
      determined. Examination of blood samples revealed that 74 of 113 raccoons (66%)
      trapped in 6 southeastern Georgia counties were infected. Seventy-three of these
      raccoons (65%) were infected with Mansonella llewellyni and this parasite was
      observed in raccoons from every location examined. Dirofilaria tenuis was found
      in 22 raccoons (20%) and was observed in only 3 of the 6 counties surveyed. An
      adult specimen of Acanthocheilonema procyonis was found in the subcutaneous
      tissues of 1 of 5 necropsied raccoons. This is the first record of filariae in
      raccoons from Georgia. In addition, Dirofilaria-like larvae were found in Aedes
      taeniorhyncus mosquitoes collected in Liberty County.

PMID- 8885905
TI  - Comparison of serodiagnostic tests and ultrasonography for cystic hydatidosis in
      an epidemiological study of rural Uruguay.
AB  - Cystic hydatidosis (CH) caused by Echinococcus granulosus is an important
      zoonosis worldwide. Several serodiagnostic and ultrasound tests are currently
      used for screening asymptomatic CH. The sensitivity of the serodiagnostic tests
      has been demonstrated by several groups to be lower than ultrasonography (US). To
      explain the mechanism of the difference in sensitivity, a large-scale US survey
      combined with an IgG4-enzyme-linked immunosorbent assay test was conducted in
      Uruguay. Our results suggest that certain cyst images, e.g., multivesicular
      cysts, may be closely associated with a high antibody response regardless of the
      cyst size, whereas other hydatid lesions, e.g., solid images with/without rolled
      parasite membranes, have lower antibody responses with a close relationship to
      cyst size. Seropositivity of subjects who had been treated surgically for removal
      of hydatid cysts in the last 5 yr was closest to that of actual CH patients,
      albeit free from CH by US. These findings are important for the proper use of
      serodiagnostic tests and US for community-based epidemiological studies.

PMID- 8885906
TI  - Efficacy of estrogen supplementation in the treatment of urinary incontinence.
      The Continence Program for Women Research Group.
AB  - OBJECTIVE: To assess the efficacy of cyclic postmenopausal hormone replacement in
      treating urinary incontinence in hypoestrogenic women. METHODS: Eighty-three
      hypoestrogenic women complaining of urinary incontinence were included. All
      patients were community-dwelling, age 45 years or older, with involuntary loss of
      urine occurring at least once a week and urodynamic evidence of genuine stress
      incontinence and/or detrusor instability. Evaluation consisted of a comprehensive
      clinical and urodynamic research protocol. The hypoestrogenic entry criterion was
      a plasma estradiol level of 30 pg/mL or less. Parabasal cells on vaginal smears
      were also monitored. The primary outcome was the number of incontinent episodes
      per week, as documented on a standardized urinary diary. Secondary outcomes were
      the quantity of fluid loss, voluntary diurnal and nocturnal micturition
      frequency, generic and condition-specific health-related quality of life
      measurements, and patient satisfaction. A randomized, placebo-controlled, double
      blind design was used. Subjects in the treatment group were given conjugated
      equine estrogens (0.625 mg) and medroxyprogesterone (10 mg) cyclically for 3
      months. Controls received placebo tablets. RESULTS: (All results are presented as
      mean +/- standard deviation.) Subjects were 67 +/- 9 years old. The menopause
      duration was 18 +/- 11 years. The duration of incontinence was 9 +/- 9 years.
      Estradiol level at baseline was 9 +/- 9 pg/mL, and the parabasal cell count was
      42 +/- 44%. The number of incontinent episodes at baseline was 13 +/- 10 for the
      treatment group and 16 +/- 4 for controls. No significant changes occurred in the
      number of incontinent episodes after treatment: 10 +/- 10 for the treatment
      group, and 13 +/- 14 for the controls (P = .7). Also, fluid loss was not changed:
      176 +/- 106 g for the treatment group and 64 +/- 88 g for the control group at
      baseline, and 101 +/- 150 and 51 +/- 69 g after treatment, respectively (P = .7).
      There were no significant differences for either diurnal or nocturnal voluntary
      micturition, quality of life measures, or patient's perception of improvement.
      CONCLUSION: Three-month cyclic hormone replacement therapy did not affect either
      clinical or quality of life variables of incontinent, hypoestrogenic women. Long
      term effects are unlikely to be substantially different. The use of estrogen
      supplementation as preventive or adjuvant therapy was not evaluated in this
      study.

PMID- 8885907
TI  - Magnetic resonance imaging anatomy of the female urethra: a direct histologic
      comparison.
AB  - OBJECTIVE: To define the urethral structures visible on magnetic resonance
      imaging (MRI) relevant to stress urinary incontinence. METHODS: The urethra and
      surrounding tissues were harvested from 13 female cadavers (ages 21-81) and fixed
      in 10% buffered formalin. High-resolution T1- and T2-weighted images were
      obtained at 1.5 tesla. Mallory trichrome-stained histologic sections were
      prepared in corresponding planes from the cadaveric specimens. Immunohistologic
      stains for smooth muscle (actin) and vascular endothelium (CD-34 and factor VIII)
      were obtained on two specimens. Histology and MRI were compared using side-by
      side correlation of projected images and by superimposing projected images.
      Comparison was also made to a non-cadaveric urethral MRI of a 29-year-old woman
      and to the MRI of another specimen imaged pre- and post-fixation. RESULTS:
      Distinct layers of the cadaveric urethra were seen best on proton density and T2
      weighted images. From the center to the periphery, a series of concentric rings
      were visible: an inner bright ring, the mucosa; a dark ring, the submucosa; an
      outer bright ring, the smooth muscle of the urethra in a loose connective tissue
      matrix; and a peripheral dark ring, the striated urogenital sphincter muscle of
      the urethra in dense connective tissue. No significant alterations were caused by
      fixation. These cadaveric images matched the non-cadaveric MRI of the 29-year-old
      woman. CONCLUSION: The internal urethral anatomy visible on high-resolution MRI
      can be identified and confirmed histologically, and these findings may form the
      basis for future anatomic investigation of stress urinary incontinence and other
      urethral abnormalities.

PMID- 8885908
TI  - Pelvic floor stimulation in the treatment of mixed incontinence complicated by a
      low-pressure urethra.
AB  - OBJECTIVE: To determine the efficacy and safety of transvaginal pelvic floor
      stimulation in the treatment of women with genuine stress incontinence and
      detrusor instability complicated by a low-pressure urethra. METHODS: Twenty-six
      consecutive women with mixed incontinence complicated by a low-pressure urethra
      who elected to try pelvic floor stimulation were studied. Visual analogue symptom
      scales and weekly incontinence episodes were compared before and after 8 weeks of
      twice-daily device use. RESULTS: The symptoms of stress and urge incontinence
      were completely resolved in six (23%) and ten (38%) women, respectively. Ten of
      26 subjects (38%) had greater than 50% overall symptomatic improvement, and two
      subjects (8%) were completely dry during their last week of therapy. Symptoms of
      urinary frequency, urgency, and stress incontinence improved significantly. No
      factors were found to be predictive of treatment success. CONCLUSION: Pelvic
      floor stimulation was found to be an effective and safe treatment for some
      patients with genuine stress incontinence and detrusor instability complicated by
      a low-pressure urethra.

PMID- 8885909
TI  - The effect of dilute vasopressin solution on blood loss during operative
      hysteroscopy: a randomized controlled trial.
AB  - OBJECTIVE: To assess the effect of intracervical injection of dilute (0.05 U/mL)
      vasopressin solution on blood loss during operative hysteroscopy. METHODS: In a
      randomized, double-blind study, dilute vasopressin solution or placebo (normal
      saline) was injected into the cervical stroma of 106 women before dilation of the
      cervix in preparation for operative hysteroscopy. Intraoperative bleeding was
      calculated by dividing the number of red blood cells per milliliter of outflow
      distention fluid by the number of red blood cells per milliliter of the woman's
      blood immediately before the procedure and multiplying this quotient by the total
      amount of outflow fluid collected. Pressures were kept constant with a
      hysteroscopic infusion pump. RESULTS: The mean (+/-standard error of the mean)
      intraoperative blood loss of the treated (vasopressin) and control (placebo)
      groups was 20.3 +/- 4.1 mL (range 0-135) and 33.4 +/- 5.4 mL (range 0-290),
      respectively. The volume of distention fluid intravasation in the treated and
      control groups was 448.5 +/- 47.0 mL (range 30-1410) and 819.1 +/- 79.7 mL (range
      20-1977), respectively. The operating time in the treated and control groups was
      31.1 +/- 1.2 minutes (range 18-52) and 34.1 +/- 1.3 minutes (range 19-65),
      respectively. For all three outcome measures, the differences between the two
      groups were statistically significant, but for visual clarity of the uterine
      cavity during surgery, the difference was not significant. CONCLUSION:
      Administration of dilute vasopressin solution (0.05 U/mL) to the cervical stroma
      significantly reduces blood loss, distention fluid intravasation, and operative
      time during hysteroscopy. Further evaluation is required to determine the optimum
      dosage.

PMID- 8885910
TI  - Hormone replacement therapy after transcervical resection of the endometrium.
AB  - OBJECTIVE: To determine if women who have undergone transcervical resection of
      the endometrium can be treated safely with estrogens alone. METHODS: Sixty-two
      postmenopausal women who had undergone endometrial resection were recruited into
      a double-blind, randomized study. Twenty-one had menopausal symptoms at the
      primary operation and were recruited at the time of the surgery, and 38 were
      recruited an average of 20 months (range 8-42) after the primary endometrial
      resection and underwent a second resection to remove any residual endometrium
      before entering the study. Three patients were excluded from the study. Subjects
      were allocated randomly to one of two hormone replacement therapy (HRT) regimens:
      17-beta-estradiol 2 mg alone or combined with norethisterone 1 mg. Clinical and
      ultrasound data were collected every 3 months. Hysteroscopically standardized
      endometrial biopsies were taken after 1 year. RESULTS: In the single-agent
      therapy group, endometrial hyperplasia without atypia was found in six subjects
      and proliferative endometrium in eight after 1 year. No such cases occurred among
      women receiving combined therapy. Endometrial thickness and menstrual bleeding
      were significantly greater in the single-agent therapy group than in those
      receiving combined therapy. These differences between single-agent and combined
      therapy were statistically significant. CONCLUSION: Postmenopausal HRT in
      patients who have undergone transcervical resection of the endometrium should
      include progestagen for protection of the endometrium.

PMID- 8885911
TI  - The risk of carbon monoxide poisoning after prolonged laparoscopic surgery.
AB  - OBJECTIVE: To evaluate whether thermal energy produced by laser and bipolar
      electrosurgery during laparoscopic procedures significantly elevates blood
      carboxyhemoglobin levels. METHODS: We prospectively studied 27 healthy nonsmoking
      patients, mean +/- standard deviation (SD) age 39.1 +/- 8.0 years (range 22-56),
      scheduled for laparoscopic procedures in which smoke was generated. Prolonged
      operative laparoscopy involved high-flow carbon dioxide insufflation, intensive
      evacuation of intra-abdominal smoke, and controlled hyperventilation with 50-100%
      oxygen. Laser and bipolar electrosurgery were used in all cases. Blood samples
      were drawn before and after surgery. Carboxyhemoglobin concentrations were
      measured using a highly accurate gas chromatography method. RESULTS: The mean +/-
      SD duration of surgery was 141 +/- 72 minutes (range 45-300). The mean +/- SD
      carboxyhemoglobin levels were 0.70 +/- 0.15% (range 0.44-1.20%) before surgery
      and 0.58 +/- 0.20% (range 0.30-1.33%) after surgery. A significant decrease (P <
      .001) in carboxyhemoglobin concentrations occurred during surgery (mean +/- SD,
      20 +/- 11%; range 3-46%). The carboxyhemoglobin level was increased at the end of
      surgery in only one woman. In only one patient did the levels exceed 1% (1.33%),
      still well below the human threshold tolerance level of 2%. The Spearman
      correlation coefficient between carboxyhemoglobin concentrations and duration of
      surgery was r = 0.308 (P = .12). CONCLUSION: Carbon monoxide (CO) poisoning is
      not associated with even prolonged laparoscopic surgical procedures. This may be
      attributed to aggressive smoke evacuation that minimizes exposure to CO, and to
      active elimination of CO by ventilation with high oxygen concentrations.

PMID- 8885912
TI  - Low-dose oral methotrexate with expectant management of ectopic pregnancy.
AB  - OBJECTIVE: To investigate recovery times and need for laparoscopy in women with
      ectopic pregnancy who were treated for 5 days 2.5 mg/day of oral methotrexate or
      placebo. METHODS: Sixty women with ectopic pregnancy among patients of an
      outpatient clinic specializing in early pregnancy disorders were selected for
      medical treatment in a double-blind, placebo-controlled study. The diagnosis was
      made by transvaginal sonography and serum hCG determinations, either at admission
      or after repeated examinations. Women were recruited for the study if they had
      mild symptoms: the hCG increase was less than 50% within 2 days, the diameter of
      the ectopic pregnancy was less than 40 mm, there were no signs of intra-abdominal
      bleeding by transvaginal sonography, and there were no secondary reasons for
      laparoscopy. Either 2.5 mg of methotrexate or placebo was given orally for 5
      days. Serum hCG was determined after 2 days, and hCG, red blood cell count, white
      blood cell count, platelet count, and serum glutamic-oxaloacetic transaminase
      were measured; transvaginal sonography was performed after 5 and 12 days.
      Expectant management was continued individually with check-ups at 1-3-week
      intervals. Laparoscopy was performed if the patient developed abdominal pain or
      intra-abdominal hemorrhage, as seen by transvaginal sonography. Statistical
      analysis was by paired or unpaired t test, Mann-Whitney U test, regression
      analysis, and repeated measures analysis of variance. RESULTS: Seventy-seven
      percent of the patients recovered without the need for laparoscopy in both
      groups, and there were no significant differences in recovery times or the need
      for laparoscopy between groups. CONCLUSION: Oral methotrexate, 2.5 mg for 5 days,
      does not appear to be more effective than placebo in the treatment of ectopic
      pregnancy in women eligible for expectant management.

PMID- 8885913
TI  - Relationship of ovarian stromal blood flow at the baseline ultrasound scan to
      subsequent follicular response in an in vitro fertilization program.
AB  - OBJECTIVE: To assess whether Doppler indices of intraovarian blood flow are
      related to the subsequent follicular response in an in vitro fertilization (IVF)
      program. METHODS: One hundred five women underwent ultrasonographic assessment of
      ovarian morphology, transvaginal color Doppler measurement of intraovarian blood
      flow and immunoassay of serum FSH during the early follicular phase of an IVF
      cycle. The subsequent follicular response was related to the Doppler data.
      RESULTS: Mean ovarian stromal peak systolic blood flow velocity was significantly
      correlated with the follicular response (P = .001), even after adjusting for the
      age of patient, type of ovary (polycystic or normal), total number of human
      menopausal gonadotropin ampules used, and serum FSH. Mean ovarian stromal
      pulsatility index was not related to the follicular response. Mean ovarian
      stromal peak systolic blood flow velocity was significantly lower (P = .007) in
      the poor-response group. The adjusted odds of a poor response increased
      significantly by an estimated 22% per cm/second decrease in velocity (P = .02).
      CONCLUSION: Ovarian stromal blood flow at the baseline ultrasound scan is
      correlated with subsequent follicular response and may be a new indicator for
      predicting ovarian responsiveness in an IVF program.

PMID- 8885914
TI  - The effects of smoking on ovarian function and fertility during assisted
      reproduction cycles.
AB  - OBJECTIVE: To investigate the effects of cigarette smoking on ovarian function
      and fertility in women undergoing assisted reproduction cycles. METHODS: We
      assessed the effects of smoking on ovarian function and fertility in a cohort of
      499 women. Questionnaires were designed to quantify past smoking exposure and to
      determine whether the woman was smoking during the treatment cycle. Ovarian
      function characteristics and pregnancy rates were compared among current smokers,
      past smokers, and nonsmokers. RESULTS: Compared with nonsmokers, both current and
      past smokers have reduced gonadotropin-stimulated ovarian function. A history of
      increasing tobacco exposure was associated with decreasing serum estradiol
      concentrations, numbers of retrieved oocytes, and numbers of embryos. On average,
      for every 10 pack-years of cigarette smoking, 2.5 fewer mature oocytes and 2.0
      fewer embryos were obtained. Women who smoked during their treatment cycle had
      approximately a 50% reduction in implantation rate and ongoing pregnancy rate
      compared with women who had never smoked. Women who quit smoking before their
      treatment cycle had the same pregnancy rate as nonsmokers. CONCLUSION: Cigarette
      smoking is associated with a prolonged and dose-dependent adverse effect on
      ovarian function. Smoking appears to have a more transient toxic effect on
      fertility, because current smokers, but not past smokers, had a markedly reduced
      pregnancy rate after treatment cycles compared with nonsmokers. Women should quit
      smoking before assisted reproduction cycles.

PMID- 8885915
TI  - Salivary progesterone concentrations after tubal sterilization.
AB  - OBJECTIVE: To find out if ovarian endocrine function is hampered by laparoscopic
      tubal sterilization. METHODS: Salivary progesterone levels were measured in 55
      women undergoing a laparoscopic tubal sterilization with Hulka or Filshie clips.
      The participants were 31-43 years old (mean 37) and were menstruating regularly.
      The saliva was collected every morning during three menstrual cycles: on the
      cycle preceding sterilization, and 3 and 12 months after the procedure. Salivary
      progesterone levels were determined by a radioimmunoassay. RESULTS: Total
      progesterone secreted in the luteal phase declined slowly after the
      sterilization, resulting in the lowest values 1 year after the procedure (1780 +/
      807 versus 2431 +/- 1187 pmol/L before surgery, P = .001). The luteal peak
      progesterone values were lowest 3 months after sterilization (277 +/- 137
      pmol/L). Although the peak progesterone secretion seemed to have started to
      recover at 12 months (318 +/- 171 pmol/L), it was still significantly less than
      before surgery (378 +/- 150 pmol/L, P = .015). The length of the entire menstrual
      cycle and the lengths of the follicular and luteal phases were not affected.
      CONCLUSION: Although the menstrual pattern was not affected, laparoscopic tubal
      sterilization caused measureable changes in the luteal function. However, these
      changes may be temporary in nature.

PMID- 8885916
TI  - Maternal position during labor: effects on fetal oxygen saturation measured by
      pulse oximetry.
AB  - OBJECTIVE: To determine the effects of maternal left lateral, right lateral, and
      supine positions during labor on fetal oxygen saturation measured by pulse
      oximetry. METHODS: Fetal oxygen saturation measured by pulse oximetry was
      obtained in 15 laboring women randomly and successively adopting left lateral,
      supine, and right lateral positions for 10 minutes each. Repeated measures
      analysis of variance was used for statistical analysis. RESULTS: Changes in fetal
      oxygen saturation were observed in different maternal positions. The supine
      position was associated with a lower fetal oxygen saturation than the left
      lateral position. One supine hypotensive syndrome occurred and was associated
      with a drop in fetal oxygen saturation. CONCLUSION: Maternal supine position
      during labor is associated with a lower fetal oxygen saturation than the left
      lateral position.

PMID- 8885917
TI  - Preterm premature ruptured membranes: a randomized trial of steroids after
      treatment with antibiotics.
AB  - OBJECTIVE: To assess the effectiveness of corticosteroids in patients with
      preterm premature rupture of membranes (PROM) after treatment with a broad
      spectrum antibiotic, ampicillin-sulbactam. METHODS: A randomized clinical trial
      of corticosteroids in patients with preterm PROM was undertaken after treating
      these patients for a minimum of 12 hours with ampicillin-sulbactam. No digital
      vaginal examinations were performed on these patients. Antibiotics were continued
      for 7 days and the steroids were repeated weekly. No tocolytics were used. The
      primary outcome measure was the incidence of respiratory distress syndrome (RDS).
      Secondary outcome measures included latency period and neonatal and maternal
      infectious morbidity. RESULTS: Seventy-seven patients were enrolled and data
      about their pregnancies were analyzed. No statistically significant difference in
      latency period was noted (14.7 days in the steroid group, 15.8 days in the no
      steroid group). Both neonatal and maternal infectious morbidity were similar. A
      significant reduction in the incidence of RDS (18.4 versus 43.6%, P = .03) were
      observed in the steroid group. CONCLUSION: These data suggest that treating
      preterm PROM patients with a broad-spectrum antibiotic before corticosteroids
      decreases RDS without apparent adverse sequelae.

PMID- 8885918
TI  - The usefulness of a prenatal genetic questionnaire in genetic risk assessment.
AB  - OBJECTIVE: To evaluate a prenatal questionnaire as a genetic screen and as an aid
      in pre-amniocentesis genetic risk assessment. METHODS: In a retrospective cohort
      study, charts were reviewed for 158 consecutive women of advanced maternal age
      referred for genetic counseling. Genetic risks identified by use of a
      questionnaire completed by 79 consecutive patients were compared with those risks
      identified by the referring physician, those identified during subsequent three
      generation pedigree analysis, and to genetic risks identified by pedigree
      evaluation of 79 consecutive individuals who underwent genetic counseling without
      the aid of a questionnaire (controls). RESULTS: Sixteen (20%) of the
      questionnaires revealed a previously unidentified genetic risk. The sensitivity
      and specificity of the questionnaire were determined to be 40.0 and 97.4%,
      respectively. Pedigree analysis alone (control group) identified significantly
      more at-risk pedigrees than did the questionnaire alone (34 versus 20%, P < .05),
      but identified significantly fewer at-risk pedigrees than obtained from the study
      group patients who completed a questionnaire and pedigree evaluation (34 versus
      50.6%, P < .05). Of all 158 patients, 15.2% (n = 24) underwent additional testing
      on the basis of genetic risk assessment. There was no difference between the
      study and control groups in additional evaluations performed (P = 1.0).
      CONCLUSION: A three-generation pedigree is superior to a questionnaire in genetic
      risk assessment. The questionnaire was not sufficiently sensitive to serve
      independently as an adequate genetic screen or risk assessment tool and did not
      influence subsequent fetal evaluation. Assessment of the sensitivity and
      specificity of prenatal genetic questionnaires should be undertaken before their
      routine clinical use.

PMID- 8885919
TI  - The accuracy of late antenatal screening cultures in predicting genital group B
      streptococcal colonization at delivery.
AB  - OBJECTIVE: To determine the accuracy of late antenatal anogenital cultures in
      predicting group B streptococcal colonization at delivery. METHODS: Swabs of the
      vagina and rectum were obtained from 826 women during routine prenatal visits at
      approximately 35-36 weeks' estimated gestation. The same women were recultured at
      admission for delivery. Swabs were cultured in broth media. Test performance
      indices were calculated using culture status at the time of delivery as the
      reference. Based on the sensitivity and specificity of antenatal cultures derived
      from analysis of this study population, we estimated predictive values of late
      antenatal cultures for a range of group B streptococcal carriage rates. RESULTS:
      Group B streptococci were identified in specimens from 219 of 826 women (26.5%).
      The sensitivity of late antenatal cultures for identifying colonization status at
      delivery was 87% (95% confidence interval [95% CI] 83-92). Specificity was 96%
      (95% CI 95-98). Positive predictive value was 87% (95% CI 83-92), and negative
      predictive value was 96% (95% CI 95-98). Test performance was similar from 1-5
      weeks before delivery, but declined when 6 or more weeks had elapsed between the
      antenatal culture and delivery. Among patients cultured 6 or more weeks before
      delivery, sensitivity was only 43%, specificity 85%, and positive and negative
      predictive values were 50 and 81%, respectively. We estimated positive and
      negative predictive values of 85 and 97% for a colonization rate of 20%, and 79
      and 98% for a colonization rate of 15%. CONCLUSION: Anogenital cultures in broth
      media obtained during the late antenatal period are accurate in predicting group
      B streptococcal colonization status at delivery in term parturients, and they
      perform significantly (P < .01) better than cultures collected 6 or more weeks
      before delivery.

PMID- 8885920
TI  - The association between maternal serum alpha-fetoprotein and preterm birth, small
      for gestational age infants, preeclampsia, and placental complications.
AB  - OBJECTIVE: To determine whether high levels of serum alpha-fetoprotein (AFP)
      predict increased risk of adverse pregnancy outcomes, including preterm birth
      (before 37 weeks), preterm birth occurring at or before 28 weeks, small for
      gestational age (SGA) infant, preeclampsia, and placental abnormalities, and to
      determine whether low levels of serum AFP predict increased or decreased risk of
      these outcomes. METHODS: Using the mother's first name, last name, and zip code,
      we linked the records of 51,008 women who participated in the California Alpha
      Fetoprotein Screening Program between June 15, 1986, and October 31, 1987, with
      California birth certificates for singleton infants born in 1987. The accuracy of
      the data linkage was confirmed by manually examining complete names, mother's
      ethnicity, and mother's age for a sample of 500 of the mother-infant linkages.
      Blood samples were obtained at 15-19 weeks. RESULTS: A strong gradient of
      increasing risk of preterm birth with increasing levels of serum AFP was observed
      (test for trend, P < .01). Among women with high levels of serum AFP (at least
      2.5 multiples of the median [MoM]), 24.3% had preterm births, compared with 3.8%
      of women with low levels of serum AFP (0.81 MoM or less), odds ratio 8.7, 95%
      confidence interval 7.1-10.7). This gradient persisted when preterm infants of 28
      weeks or less were examined separately. Similar gradients were observed for the
      risk of preeclampsia and placental abnormalities. There was a weaker U-shaped
      relation between serum AFP level and the risk of an SGA infant. CONCLUSION: Low
      levels of second-trimester maternal serum AFP are associated with a very low risk
      of preterm birth, preeclampsia, and placental complications. High levels of serum
      AFP are strongly associated with preterm birth, preeclampsia, and placental
      abnormalities. There is a modest association between AFP levels (both low and
      high) and SGA birth.

PMID- 8885921
TI  - Comparisons of outcomes of maternity care by obstetricians and certified nurse
      midwives.
AB  - OBJECTIVE: To determine whether pregnancy outcomes differ by provider group when
      alternative explanations are taken into account. METHODS: Pregnancy outcomes were
      compared for 710 women cared for by private obstetricians and 471 cared for by
      certified nurse-midwives. At intake, all women qualified for nurse-midwifery
      care. They were retained in their original group for analysis, even if they were
      later referred to physicians. Infant and maternal mortality, 30 clinical
      indicators, satisfaction with care, and monetary charges were studied. The study
      site's history and philosophy of honoring consumer choice of provider precluded
      random assignment, but multivariate analyses minimized the effects of multiple
      confounding factors. The statistical power was adequate for the study design.
      RESULTS: Significant differences (P < .05) between the obstetrician and nurse
      midwife groups were found for seven clinically important outcomes: infant
      abrasions (7 versus 4%), infant remaining with mother for the entire hospital
      stay (15 versus 27%), third- or fourth-degree perineal laceration (23 versus 7%),
      number of complications (0.7 versus 0.4), satisfaction with care, average
      hospital charges ($5427 versus $4296), and average professional fee charges
      ($3425 versus $3237). When maternal risk, selection bias, and the medical
      intensiveness of care were controlled, the provider group did not continue to
      have an independent effect on infant abrasions, hemorrhage, and professional fee
      charges; when women's preferences were added, the difference in hospital charges
      disappeared. However, the provider group continued to have significant
      independent effects on the other four outcomes. Interaction effects were not
      significant. CONCLUSION: Although most outcomes were equally good, important
      differences between obstetrician and nurse-midwife care remained after
      multivariate analysis.

PMID- 8885922
TI  - Sonographic visualization of the ovaries throughout pregnancy.
AB  - OBJECTIVE: To determine the frequency with which one or both normal ovaries can
      be visualized during a routine obstetric ultrasound examination. METHODS: The
      population consisted of 5617 pregnant women at 5.0-39.9 weeks' gestation, studied
      cross-sectionally. The sonographic visualization rate for one or both normal
      ovaries, as well as their position above or below the level of the umbilicus, was
      recorded for one examination in each patient. RESULTS: The study population was
      divided into three groups according to gestational age: first trimester, 5.0-12.9
      weeks; second trimester, 13.0-26.9 weeks; and third trimester, 27.0-39.9 weeks.
      There were 829, 3195, and 1593 women in the first, second, and third trimesters,
      respectively. Most women were examined transvaginally in the first trimester;
      transabdominal sonography was used in the second and third trimesters. The
      ability to visualize one or both ovaries declined significantly (P < .05) from
      the first trimester to the second, as well as from the second trimester to the
      third (P < .001). The percentage of ovaries that were visualized above the
      umbilicus increased from 2.4% in the first trimester to 10.1% in the second
      trimester (P < .001), and to 21.7% in the third trimester (P < .001). CONCLUSION:
      As gestational age advances, there is a significant reduction in the ultrasound
      visualization rate of normal ovaries. This investigation provides normative data
      for ovarian visualization throughout pregnancy that may be helpful in
      establishing ultrasound laboratory standards.

PMID- 8885923
TI  - Change in fetal urine production rate in growth-restricted fetuses after maternal
      meal ingestion.
AB  - OBJECTIVE: To determine if fetal urine production is affected by maternal meal
      ingestion in growth-restricted fetuses. METHODS: We studied 25 normal-growth
      fetuses in uncomplicated pregnancies and 15 growth-restricted fetuses, all after
      30 weeks' gestation. Serial fetal bladder volume measurements were obtained at 2
      3 minute intervals with ultrasonography 2 hours before and 2 hours after maternal
      breakfast. The hourly fetal urine production rate in each maternal state was
      calculated from the bladder volume measurements. The amniotic fluid index (AFI)
      and the pulsatility index of both umbilical and fetal middle cerebral arteries
      were also measured. RESULTS: Two of the 15 growth-restricted fetuses were
      excluded from analysis, one because it was anomalous and the other because it was
      not small for gestational age at birth. In the normal-growth fetuses, the hourly
      fetal urine production rate increased significantly after maternal breakfast
      (mean +/- standard deviation 30.2 +/- 11.7 versus 41.1 +/- 14.6 mL/hour, P <
      .001). In contrast, in the growth-restricted fetuses, the rate did not change
      after maternal breakfast (24.6 +/- 6.2 versus 24.9 +/- 5.7 mL/hour). Although the
      urine production rate before breakfast did not differ between groups, 2 hours
      after maternal breakfast it was significantly lower in the growth-restricted
      fetuses than in the control group (normal-growth) (P < .001). The AFI also was
      significantly lower in the growth-restricted fetuses than in the control group
      (15.0 +/- 3.5 versus 18.6 +/- 5.0 cm, P < .04). There were no significant
      differences in the pulsed Doppler studies. CONCLUSION: In contrast to normal
      growth fetuses, maternal meal ingestion for growth-restricted fetuses does not
      increase fetal urine production. Decreased fetal urine production in the maternal
      fed state may lead to decreased amniotic fluid volume in growth-restricted
      fetuses without obvious hypoxia.

PMID- 8885924
TI  - The effect of isosorbide dinitrate on uterine artery and umbilical artery flow
      velocity waveforms at mid-pregnancy.
AB  - OBJECTIVE: To study the effect of isosorbide dinitrate, a nitric oxide donor, on
      the maternal cardiovascular system and on uterine and umbilical artery blood flow
      velocities in mid-pregnancy. METHODS: Eighteen women with low-risk pregnancy at
      17-24 weeks' gestation were given a single 5-mg dose of sublingual isosorbide
      dinitrate, a nitrovasodilator. Blood flow velocity waveforms in the ascending
      uterine artery and in the umbilical artery were measured by an image-directed,
      pulsed color Doppler ultrasound scan before and after the medication was
      administered. Maternal blood pressure (BP) and heart rate were also obtained.
      RESULTS: The mean arterial BP decreased from 86 mmHg (95% confidence interval
      [CI] 72-99) to a nadir of 73 mmHg at 6 minutes (95% CI 61-85, P < .04). Mean
      maternal heart rate increased from 85 beats per minute (95% CI 80-90) to 96 beats
      per minute at 6 minutes (95% CI 87-105, P < .01). Mean systolic-diastolic flow
      velocity ratio (S/D) in the umbilical artery rapidly declined from 4.18 (95% CI
      3.80-4.56), reaching a nadir of 3.12 at 6 minutes (95% CI 2.65-3.84, P < .001).
      The S/D in the uterine artery decreased from 4.83 (95% CI 3.99-5.56) to a nadir
      of 4.02 at 10 minutes (95% CI 3.41-4.63, P < .001). CONCLUSION: Isosorbide
      dinitrate, a donor of nitric acid, lowers mean maternal BP and reduces the
      Doppler impedance in the umbilical and uterine arteries. This drug could prove to
      be beneficial when endothelial cell dysfunction leads to insufficient synthesis
      and release of endothelium-derived relaxing factor, resulting in generalized
      vasoconstriction and increased resistance to flow in the uteroplacental
      circulation.

PMID- 8885925
TI  - Reduction of false-positive diagnosis of fetal growth restriction by application
      of customized fetal growth standards.
AB  - OBJECTIVE: To evaluate the clinical performance of fetal growth charts adjusted
      for individual maternal characteristics. METHODS: The study group consisted of
      267 low-risk singleton pregnancies with normal clinical outcome. Mothers were
      recruited prospectively after the booking visit, then underwent three to five
      ultrasound examinations for fetal weight estimation. Individual growth curves
      were generated from these data and the birth weight, based on logpolynomial
      growth model. Computer software was written to calculate the number of fetal
      growth curves that cross the tenth percentile limit, based on an unadjusted,
      average ultrasound standard for our population, compared with the number that
      cross this limit if it is customized for known pregnancy characteristics such as
      maternal height, booking weight, parity, and ethnic group. RESULTS: Individual
      growth trajectories of this group of pregnancies with normal outcome were
      significantly less likely to cross below the tenth percentile for fetal weight
      when using customized growth charts than when the unadjusted standard was used
      (McNemar's test, P < .001). CONCLUSION: The relationship between maternal
      characteristics and fetal size needs to be considered in the assessment of fetal
      growth. The use of a customized standard reduces the false-positive rate for the
      diagnosis of growth restriction in a normal population.

PMID- 8885926
TI  - Sonographic estimation of fetal body composition with gestational diabetes
      mellitus at term.
AB  - OBJECTIVE: To derive models and equations for estimating fetal lean mass and fat
      mass in women with gestational diabetes mellitus (GDM), using sonographic
      techniques and neonatal total body electrical conductivity. METHODS: Twenty women
      with GDM at term underwent sonographic evaluation within 72 hours before
      delivery. Sonographic studies included measurements of the fetal biparietal
      diameter, head circumference, abdominal circumference, anterior and lateral
      abdominal-wall subcutaneous fat thicknesses, femur length, mid-thigh
      circumference, and anterior and lateral thigh subcutaneous fat thicknesses.
      Within 24 hours of birth, the infants were weighed and their body composition
      estimated with total body electrical conductivity measurements. Volume-based
      models and regression equations for estimating lean and fat mass were derived.
      The equations were validated prospectively in the next 16 women with GDM.
      RESULTS: There were no significant differences in maternal or neonatal
      demographic or anthropometric data between the derivative and validation groups.
      The equation for estimating fetal lean mass is: lean mass = 0.169(volume of head)
      + 0.262(volume of lean trunk) - 308.59 (r = 0.86, P < .01). The equation for
      estimating fetal fat mass is: fat mass = 0.241(volume of fat sheath of trunk) -
      213.13 (r = 0.73, P < .01). In the validation group, the sonographic estimates of
      fetal lean and fat mass were not significantly different than those estimated by
      total body electrical conductivity (P = .18 and P = .77, respectively).
      CONCLUSION: Fetal body composition can be estimated by obtaining several
      additional measurements during routine fetal sonography.

PMID- 8885927
TI  - Prenatal determination of chorionicity in triplet pregnancy by ultrasonographic
      examination of the ipsilon zone.
AB  - OBJECTIVE: To determine chorionicity in triplet pregnancies by ultrasonographic
      assessment of the ipsilon zone, the junction of the three interfetal membranes.
      METHODS: The thickness of the component membranes in the ipsilon zone was studied
      to determine chorionicity in 28 triplet pregnancies, by retrospective examination
      of the ultrasonographic images taken at 9-24 weeks' gestation, and in 20
      consecutive triplet pregnancies followed prospectively by targeted
      ultrasonography at 8-21 weeks' gestation. Prenatal ultrasonographic findings were
      compared with those obtained from the records of the infertility centers or
      referring hospitals (the number of gestational sacs and live embryos in each sac
      seen by transvaginal scanning at 6-7 weeks' gestation). RESULTS: Of the 28
      triplet pregnancies with appropriate images demonstrating the ipsilon zone, 22
      were classified as trichorionic, five dichorionic, and one monochorionic. This
      classification was correct in all but one trichorionic pregnancy, which was
      misclassified as dichorionic. In the prospective subset (n = 20) there were 16
      trichorionic and four dichorionic triplet pregnancies. The ipsilon zone was not
      present in one case in which the interfetal membrane did not intersect. In the
      remaining 19 pregnancies, there was a complete correlation between the findings
      at the ipsilon zone and transvaginal ultrasonography at 6-7 weeks. CONCLUSION:
      Ultrasonographic assessment of the ipsilon zone is useful for predicting
      chorionicity in triplet pregnancies.

PMID- 8885928
TI  - High failure rate of postmortem karyotyping after termination for fetal
      abnormality.
AB  - OBJECTIVE: To determine the failure rate of karyotyping from samples taken after
      termination of pregnancy for fetal abnormality. METHODS: Perinatal autopsy
      reports over a 12-month period were reviewed to identify those with cytogenetic
      studies performed after termination of pregnancy for fetal abnormality. RESULTS:
      During the audit period, there were 104 terminations for fetal abnormality. In 89
      fetuses, fetal skin (n = 85), placenta (n = 62), or other samples (n = 8) were
      obtained for postmortem cytogenetic analysis. In 24 (27%) fetuses, postmortem
      tissues did not yield a karyotype result. The failure rate of post-termination
      karyotyping was significantly influenced by delivery-sampling interval, but not
      by gestational age, type of tissue sampled, use of potassium chloride, or
      aneuploidy. Of the 24 cases for which no post-termination karyotype was obtained,
      16 had had successful pre-termination karyotyping, resulting in only eight of 89
      (9%) cases in the overall series not having a final karyotype. CONCLUSION: The
      high failure rate for post-termination karyotyping suggests that a pre
      termination procedure is necessary if parents wish to have almost 100% certainty
      that cytogenetic information will be available for later genetic counseling.

PMID- 8885929
TI  - A comparison of umbilical cord blood gas values between newborns with and without
      true knots.
AB  - OBJECTIVE: To compare umbilical cord blood gas values in newborns with and
      without true knots, and to assess the potential impact of true knot formation on
      cord blood gases. METHODS: Twelve newborn infants with true umbilical cord knots
      were identified and compared with a random control population of 104 newborn
      infants without true knots. The two groups were analyzed for 11 maternal-fetal
      variables to determine if they were comparable. Subsequently, the principal
      outcome variable of the study was evaluated: a comparison between the umbilical
      arterial and venous blood gas results of the true knot and control populations.
      RESULTS: The true knot and control populations were comparable with respect to
      the maternal-fetal variables analyzed. The umbilical cord blood gas values did
      not differ between groups, except for a slightly lower umbilical artery
      bicarbonate value in the control group (22.0 mEq/L) versus the true knot group
      (24.5 mEq/L), P = .025. There was no significant difference in the incidence of
      acidemia (umbilical artery pH less than 7.20) between the two groups. CONCLUSION:
      The presence of true umbilical cord knots does not alter the incidence of
      umbilical artery acidemia or change umbilical cord blood gas values. Review of
      the pertinent obstetric literature supports the hypothesis that true umbilical
      cord knots lack clinical significance.

PMID- 8885930
TI  - The effect of glucagon on spontaneous contractility of isolated pregnant uterine
      muscle.
AB  - OBJECTIVE: To determine whether glucagon has relaxant effects on the spontaneous
      contractions of term pregnant human uterine smooth muscle in an isolated
      preparation. METHODS: Myometrial specimens were excised from the upper incisional
      surface of the lower uterine segment in seven women during elective cesarean
      delivery. The muscle strips were suspended in tissue baths and isometric tension
      was recorded. After establishing rhythmic spontaneous contractions, glucagon
      reconstituted with distilled water or the accompanying diluent was added directly
      to the bath in a cumulative manner. In the second phase of the study, the effect
      of the diluent (1.6% glycerin with 0.2% phenol) alone on muscle contractility was
      evaluated. RESULTS: Glucagon had no effect on uterine muscle concentrations when
      reconstituted with distilled water. However, glucagon reconstituted with the
      diluent decreased the contractile amplitude by 27 +/- 11% (mean +/- standard
      deviation, P < .01) and the frequency by 13 +/- 10% (P < .05) at a concentration
      of 20 micrograms/mL. At a cumulative concentration of 40 micrograms/mL, the
      reductions in amplitude and frequency were 65 +/- 13% (P < .001) and 18 +/- 14%
      (P < .01), respectively. The diluent at equivalent concentrations exerted
      relaxation similar to that produced by glucagon when reconstituted with the
      diluent. The relaxant effects were not different between the two solutions (P >
      .2, power 90%, alpha = .05). CONCLUSION: These results suggest that relaxation of
      contractions was likely caused by the diluent rather than by glucagon. We
      conclude that glucagon does not have a direct relaxant effect on spontaneous
      contraction of isolated uterine muscle obtained from term pregnant uteri.

PMID- 8885931
TI  - Role of urinary trypsin inhibitor in the maintenance of pregnancy in mice.
AB  - OBJECTIVE: To investigate the mechanisms whereby urinary trypsin inhibitor
      prevents lipopolysaccharide-induced preterm delivery in mice. METHODS: On day 15
      of pregnancy, C3H/HeNCrg female mice impregnated by Crg:B6D2F1 male mice were
      treated intraperitoneally with lipopolysaccharide (50 micrograms/kg, twice at a 3
      hour interval) to induce preterm delivery. Urinary trypsin inhibitor (2.5 x
      10(4), 7.5 x 10(4), or 25 x 10(4) units/kg, ten times at 1-hour intervals) or
      saline solution was administered intraperitoneally to the animals. RESULTS: The
      incidence of preterm delivery was significantly decreased on a dose-related basis
      by urinary trypsin inhibitor treatment. Urinary trypsin inhibitor prevented the
      morphologic and functional changes in fetal membranes and cervical ripening
      preceding the onset of preterm delivery. Urinary trypsin inhibitor also
      suppressed the increase in plasma and amniotic fluid concentrations of
      interleukin-1 alpha, interleukin-6, and tumor necrosis factor-alpha after the
      lipopolysaccharide dosing in this animal model for preterm delivery. CONCLUSION:
      Urinary trypsin inhibitor prevents the pathogenicity of preterm delivery through
      the suppression of cytokine production.

PMID- 8885932
TI  - Sacrospinous ligament colpopexy: new instrumentation applied to a standard
      gynecologic procedure.
AB  - Sacrospinous ligament colpopexy continues to be underutilized because of its
      technical difficulty. The Endo Stitch, a new laparoscopic suturing instrument,
      was used as a surgical adjunct in the performance of sacrospinous ligament
      colpopexy in nine patients with vaginal vault prolapse after hysterectomy. The
      procedures were performed with surprising technical ease.

PMID- 8885933
TI  - Folic acid supplementation--when and how.
AB  - The periconceptional intake of 400 micrograms of folic acid can prevent 50-70% of
      neural tube defects. It is difficult to achieve this intake with diet alone, even
      with the recently approved levels for grain-food fortification. Therefore, a
      daily multivitamin with folic acid is recommended for all women of childbearing
      potential. Obstetrician-gynecologists should exercise every opportunity to
      educate their patients to this end. Although raised as a concern, the potential
      of masking the megaloblastic anemia of pernicious anemia is unlikely with these
      levels of supplementation, and considering the rarity of the disease in women of
      reproductive age.

PMID- 8885934
TI  - Weight control in women: a challenge to the obstetrician-gynecologist.
AB  - Obesity is a major problem in American women, and there is great concern with
      regard to weight control among both the obese and the nonobese. Vast sums of
      money are spent in the area of weight reduction, often with little or no benefit.
      Although obesity affects longevity adversely, weight loss has not been clearly
      associated with a decrease in mortality risk. Reduction in weight, however, can
      decrease risk factors for certain diseases and improve the quality of life.
      Current methods of weight control include diet, exercise, surgery, and
      medication. Several studies have shown that, in contrast to previous supposition,
      medical management should be long term. Recent investigations into the basic
      mechanisms of appetite control, moreover, suggest that more physiologic
      management methods will be available in the near future.

PMID- 8885935
TI  - Are residents' work schedules related to their in-training examination scores?
AB  - OBJECTIVE: To study the relationship between residents' pre-test available study
      time and subsequent examination performance. METHODS: We compiled rotation
      schedules and in-training examination performances for all residents enrolled in
      the two University of Texas Medical School-Houston obstetrics and gynecology
      residencies between 1993 and 1995. Services on which the residents had rotated
      were ranked by surveying all enrolled residents as to their perceived available
      study time while on those services. A mean available study time rating was
      computed for each service, which was used to describe each resident's schedule.
      Pearson correlations between available preparation-time preceding the in-training
      examination and examination performance were calculated. "Tough" and "easy"
      rotation subgroups were defined; two-tailed t tests were performed to compare the
      in-training examination performance of these subgroups. RESULTS: No significant
      correlation was found between available study time and subsequent examination
      scores beyond that which could be accounted for by year of training. Scores of
      residents in the "tough" subgroup were not significantly different from those in
      the "easy" subgroup on any examination performance measure. For correlations at
      the one-tailed .05 level, statistical power to detect relationships predicting
      16% of variance ranges from approximately 85% for samples of 42 to 68% for
      samples of 27. CONCLUSION: Residents' in-training examination performance was not
      significantly affected by their service obligations. Altering resident monthly
      schedules is not likely to improve in-training examination performance.

PMID- 8885936
TI  - Doctor James Young Simpson, Rabbi Abraham De Sola, and Genesis Chapter 3, verse
      16.
AB  - When Dr. James Simpson began to use anesthesia in child-birth in 1846, a
      religious furor arose against its use. For many people, including many
      physicians, Genesis chapter 3, verse 16, implied that childbirth had to be a
      painful process. In 1849, the editors of one of Canada's medical journals asked
      Abraham De Sola, Canada's first rabbi, to give his interpretation of Genesis 3:16
      for the benefit of their readers, which he did in a three-part article. Using
      Hebrew biblical scholars as his source, he wrote that the correct interpretation
      of this passage was that with toil or labor shall women bring forth children,
      rather than with pain. Therefore, by using anesthesia in childbirth, physicians
      were not going against the scriptures or the word of God.

PMID- 8885937
TI  - Nitrous oxide inhalation: effects on maternal and fetal circulations at term.

PMID- 8885938
TI  - Nitrous oxide inhalation: effects on the maternal and fetal circulations at term.

PMID- 8885939
TI  - Outpatient diagnostic hysteroscopies.

PMID- 8885940
TI  - The effect of intracervical vasopressin on the systemic absorption of glycine
      during hysteroscopic endometrial ablation.

PMID- 8885941
TI  - Update on the 1987 Task Force Report on High Blood Pressure in Children and
      Adolescents: a working group report from the National High Blood Pressure
      Education Program. National High Blood Pressure Education Program Working Group
      on Hypertension Control in Children and Adolescents.
AB  - BACKGROUND: The "Report of the Second Task Force on Blood Pressure Control in
      Children-1987" developed normative blood pressure (BP) data for children and
      adolescents. These normative data are used to classify BP levels. Since 1987,
      additional BP data in children and adolescents, the use of newer classes of
      drugs, and the role of primary prevention of hypertension have expanded the body
      of knowledge regarding the classification and treatment of hypertension in the
      young. OBJECTIVE: To report new normative BP data in children and adolescents and
      to provide additional information regarding the diagnosis, treatment, and
      prevention of hypertension in children. METHODS: A working group was appointed by
      the director of the National Heart, Lung, and Blood Institute as chair of the
      National High Blood Pressure Education Program (NHBPEP) Coordinating Committee.
      Data on children from the 1988 through 1991 National Health and Nutrition
      Examination Survey III and nine additional national data sets were combined to
      develop normative BP tables. The working group members produced initial draft
      documents that were reviewed by NHBPEP Coordinating Committee representatives as
      well as experts in pediatrics, cardiology, and hypertension. This reiterative
      process occurred for 12 draft documents. The NHBPEP Coordinating Committee
      discussed the report, and additional comments were received. Differences of
      opinion were adjudicated by the chair of the working group. The final report was
      sent to representatives of the 44 organizations on the NHBPEP Coordinating
      Committee for vote. It was approved unanimously by the NHBPEP Coordinating
      Committee on October 2, 1995. CONCLUSIONS: This report provides new normative BP
      tables for children and adolescents, which now include height percentiles, age,
      and gender. The fifth Korotkoff sound is now used to define diastolic BP in
      children and adolescents. New charts have been developed to guide practicing
      clinicians in antihypertensive drug therapy selection. The primary prevention of
      hypertension in these age groups is discussed. A statement on public health
      considerations in the treatment of children and adolescents is provided.

PMID- 8885942
TI  - Nicotine patch therapy in adolescent smokers.
AB  - OBJECTIVE: To evaluate the safety, tolerance, and efficacy of 24-hour nicotine
      patch therapy in adolescent smokers who were trying to stop smoking. DESIGN:
      Nonrandomized, open-label, 6-month clinical trial. SETTING: Five public high
      schools in the Rochester, MN, area. SUBJECTS: Twenty-two adolescent smokers, aged
      13 through 17 years, with current smoking rate of 20 or more cigarettes per day
      (cpd). INTERVENTION: Daily nicotine patch therapy for 8 weeks (22 mg/d for 6
      weeks followed by 11 mg/d for 2 weeks). Weekly individual behavioral counseling
      and group support continued for 8 weeks with follow up visits at 3 and 6 months
      and a mailed survey at 1 year. MAIN OUTCOME MEASURES: Self-reported smoking
      abstinence verified by expired air carbon monoxide of 8 ppm or less, nicotine
      withdrawal symptoms, adverse experiences, and blood cotinine levels. RESULTS:
      Subjects had a mean +/- SD smoking rate of 23.3 +/- 5.0 (range, 20 to 35) cpd at
      study entry and 2.6 +/- 1.6 years of smoking; the mean age was 15.9 +/- 1.2
      (range 13 through 17) years, and 68% were girls. Of the 22 participants, 19 (86%)
      completed patch therapy, 3 (14%) had biochemically validated smoking cessation at
      week 8, and 1 continued to be smoke free at 3 and 6 months after patch
      initiation. There was a significant decrease from baseline in the mean nicotine
      withdrawal scores for days 4 and 7 of week 1 and the mean for weeks 2 through 8.
      Skin reactions were the most common adverse event. As the worst skin reactions,
      55% had erythema only, 5% had erythema and edema, and 9% had erythema and
      vesicles, whereas 32% had no skin reactions. Other reported adverse events were
      headaches (41%), nausea and vomiting (41%), tiredness (41%), dizziness (27%), and
      arm pain (23%). None of these were considered serious, life threatening, or led
      to the discontinuation of patch therapy. In adults with comparable smoking rates,
      we found that the adolescents had lower blood cotinine levels. Those smoking 20
      to 25 cpd had cotinine levels of 146 +/- 84 (adolescents) vs 260 +/- 98 (adults)
      ng/ml, and those smoking 26 to 35 cpd had levels of 169 +/- 73 vs 276 +/- 110
      ng/ml, respectively. CONCLUSION: Nicotine patch therapy seems safe in adolescent
      smokers. Placebo-controlled trials are needed to establish the efficacy of
      nicotine patch therapy in adolescents.

PMID- 8885943
TI  - Maternal smoking and pulmonary neuroendocrine cells in sudden infant death
      syndrome.
AB  - BACKGROUND: Maternal smoking is a well-recognized risk factor for sudden infant
      death syndrome (SIDS), but the precise mechanism is unknown. We tested a
      hypothesis that maternal smoking affects pulmonary neuroendocrine cells (PNECs)
      and neuroepithelial bodies (NEBs), which are innervated PNEC clusters and
      presumed airway chemoreceptors. METHODS: Lung sections from infants who died of
      SIDS and whose mothers smoked during pregnancy (n = 22), infants who died of SIDS
      and whose mothers were nonsmokers (n = 17), and age-matched control infants (n =
      15) who died of other causes were immunostained for bombesin (a PNEC and NEB
      marker) and assessed morphometrically. RESULTS: The frequency of PNEC (the
      percentage of airway epithelium immunoreactive for bombesin) was increased up to
      twofold in the lungs of infants who died of SIDS (7.7 +/- 0.4%) compared with
      controls (4.9 +/- 0.4%), as was the frequency (40 +/- 3.5 vs 23 +/- 3.7/cm2) and
      size (748 +/- 46.5 vs 491 +/- 25.8 microns2) of NEBs. In infants who died of SIDS
      and who were born to smoking mothers, PNEC frequency was increased significantly
      compared with that in those born to nonsmoking mothers, but the frequency and
      size of NEBs were not significantly different between the two groups. CONCLUSION:
      Our findings suggest that maternal smoking potentiates hyperplasia of the PNEC
      system in the lungs of infants who die of SIDS and that a dysfunction of these
      cells may contribute to the pathophysiology of SIDS.

PMID- 8885944
TI  - Laceration repair using a tissue adhesive in a children's emergency department.
AB  - OBJECTIVE: To determine the effectiveness of a tissue adhesive, Histoacryl Blue
      (HAB), for laceration repair in children. DESIGN: Prospective, randomized
      clinical trial. SETTING: A tertiary care pediatric emergency center at Egleston
      Children's Hospital. PARTICIPANTS: Children who presented for laceration repair
      between October 1994 and February 1995 were prospectively evaluated. Patients
      less than 1 or greater than 18 years of age, those with lacerations greater than
      5 cm, and those with lacerations located on the eyelids, ears, nose, lips, hands,
      feet, joints, or perineum were excluded. INTERVENTIONS: Following consent and
      routine wound management, including subcutaneous closure when deemed necessary,
      patients were randomized to receive skin sutures or HAB for cutaneous closure.
      METHODS: Length of time required for laceration repair was recorded. Parental
      perception of the pain experienced by their child was assessed using a visual
      analogue scale. Photographic documentation of scar appearance at the 2-month
      follow-up visit was evaluated by plastic surgeons using a visual analogue scale.
      RESULTS: Sixty-one children were enrolled: HAB group (N = 30), suture group (N =
      31). No differences occurred between groups in laceration length, depth,
      location, or patient demographics. Length of time required for repair was
      decreased (median, HAB 7 minutes vs suture 17.0 minutes) and parental assessment
      of their child's pain was significantly less in the HAB group. Parents were more
      likely to recommend HAB over suturing to other parents or guardians. Cosmetic
      outcome in the HAB group was assessed to be as good as, or better than, the
      cosmetic outcome in the suture group as evaluated by two plastic surgeons.
      CONCLUSION: The use of HAB for laceration repair is an acceptable alternative to
      conventional suturing with a comparable cosmetic outcome. Advantages include less
      pain to the child, no need for suture removal, and more efficient use of
      physician time. Parents were also more likely to recommend HAB over suturing for
      laceration repair.

PMID- 8885945
TI  - Paternity after unilateral cryptorchidism: a controlled study.
AB  - OBJECTIVE: To determine if paternity is decreased among formerly unilateral
      cryptorchid men compared with a control group of men. SUBJECTS AND METHODS:
      Formerly unilateral cryptorchid men who had orchiopexy between 1955 and 1971 at
      the Children's Hospital of Pittsburgh and a group of control men have had their
      medical records reviewed and have been surveyed by questionnaire. RESULTS: Among
      the men who had ever married and had attempted paternity, significantly more of
      the unilateral cryptorchid men had been unable to father children (10.5%) than
      among the control group (5.4%). No difference was found when the groups were
      compared for the duration of regular intercourse without contraception to
      conception of their first child. There was no relationship between the age of
      orchiopexy or lifestyle factors and paternity or between the age of orchiopexy
      and months of regular unprotected intercourse to conception. Paternity among both
      groups was related to female-related infertility factors and to the presence of
      varicoceles. CONCLUSION: When compared with a control group, paternity was
      compromised after unilateral cryptorchidism. Infertility is about twice as
      frequent among the unilateral group. There was no evidence of subfertility
      requiring a longer exposure of regular intercourse without contraception among
      the fertile subgroup. No correlation was found between age of orchiopexy and
      paternity.

PMID- 8885946
TI  - Clinical outcomes of children with acute abdominal pain.
AB  - OBJECTIVE: To determine the prevalence, associated symptoms, and clinical
      outcomes of children presenting for a nonscheduled visit with acute abdominal
      pain. DESIGN: Historical cohort. SETTING: Inner-city teaching hospital.
      PARTICIPANTS: A total of 1141 consecutive children, ages 2 to 12, presenting for
      a nonscheduled visit (clinic or emergency department) with a complaint of
      nontraumatic abdominal pain of < or = 3 days' duration were identified through a
      manual chart review. MEASUREMENTS: Collected data included: 1) demographic
      characteristics, 2) presenting signs and symptoms, 3) records from the hospital
      record for all children who returned within 10 days for follow-up, 4) test
      results, and 5) telephone follow-up. A clinical reviewer used the data to assign
      a final diagnosis to each patient. RESULTS: The prevalence of children presenting
      with abdominal pain of < or = 3 days' duration was 5.1%. The most common
      associated symptoms were history of fever (64%), emesis (42.4%), decreased
      appetite (36.5%), cough (35.6%), headache (29.5%), and sore throat (27.0%). The
      six most prevalent final diagnoses, accounting for 84% of all final diagnoses,
      were upper respiratory infection and/or otitis (18.6%), pharyngitis (16.6%),
      viral syndrome (16.0%), abdominal pain of uncertain etiology (15.6%),
      gastroenteritis (10.9%), and acute febrile illness (7.8%). Approximately 1% of
      children required surgical intervention (10/12 for appendicitis). Approximately
      7% of children returned within 10 days for reevaluation of their illness; on
      return, 11 had treatable medical diseases and 4 had diseases requiring surgical
      intervention. CONCLUSIONS: An acute complaint of abdominal pain in children
      occurs in 5.1% of nonscheduled visits, is frequently accompanied by multiple
      complaints, and is usually attributed to a self-limited disease. Close follow-up
      will identify the 1% to 2% who proceed to have a more serious disease process.
      This epidemiologic data will aid clinic-based physicians who manage children with
      acute abdominal pain.

PMID- 8885947
TI  - Use of health care services by inner-city infants in an early discharge program.
AB  - OBJECTIVE: To assess the use of health care services by inner-city infants
      enrolled in an early discharge program who received care in tertiary care
      children's hospital primary care clinic. DESIGN: Retrospective cohort study.
      SETTING: Large, metropolitan university hospital and a children's hospital.
      PATIENTS: Term infants cared for in a single full-term nursery, before and after
      implementation of a coordinated early discharge program, who received primary
      care at the children's hospital. INTERVENTION: The coordinated Early Discharge
      Program was characterized by in-hospital visits by hospital-based coordinating
      nurses, home visits by nurses from a home nursing agency, and communication with
      physicians for necessary adjustments in postdischarge care. METHODS: After
      linking birth hospital records and the children's hospital medical records, a
      retrospective chart review was performed to obtain maternal demographic
      information and birth hospital length of stay, as well as the infants' attendance
      at primary care clinic, immunizations, emergency department visits, and
      rehospitalization. MAIN OUTCOME MEASURES: Number of primary care visits in the
      first 3 months of life, completion of one series of immunizations by 3 months of
      life, and number of emergency department visits and rehospitalization during the
      first 3 months of life. RESULTS: The early discharge group (n = 253) had a
      significantly shorter birth hospital length of stay (35 +/- 24 hours, mean +/-
      SD) when compared with the control group (n = 212) (52 +/- 14 hours). The early
      discharge group was also younger than the control group at the first primary care
      visit, with significantly more infants visiting the primary care clinic in the
      first month of life. There was also a significant difference between the groups
      in the mean number of emergency department visits (early discharge = .61
      visits/patient, control = .79 visits/patient) and the proportion of patients with
      no emergency department visits during the first 3 months of life (early discharge
      = 57%, control = 43%). There was no difference between the two groups in the
      proportion of infants completing one series of immunizations or in the number of
      infants rehospitalized during the study period. CONCLUSIONS: Coordinated early
      discharge with home nursing visits for inner-city infants may result in earlier
      use of primary care services. Furthermore, there is a significant decrease in use
      of the emergency department during the first 3 months of life, and no increase in
      rehospitalization.

PMID- 8885948
TI  - Early identification of cerebral palsy using a profile of abnormal motor
      patterns.
AB  - OBJECTIVE: To determine whether a profile of abnormal motor patterns can identify
      children with cerebral palsy (CP) in the first year of life. METHODS: The Early
      Motor Pattern Profile (EMPP) consists of 15 items reflecting variations in muscle
      tone, reflexes, and movement that have been organized into a standardized format
      to provide the clinician with an objective picture of neurologic status. A three
      point scoring system was applied to each item, delineating a clearly normal
      response from a clearly abnormal one and placing all partial or inconsistent
      responses in the middle. Twelve hundred forty-seven high-risk infants who were
      enrolled in a neonatal intensive care unit follow-up program were examined at 6
      and/or 12 months' corrected age using the EMPP. These infants were followed to at
      least 36 months of age to distinguish those with CP from those with normal motor
      outcome or minimal impairment (no CP). RESULTS: Predictive validity of the EMPP
      at the 6- and 12-month examinations was determined using various pass-fail
      cutoffs. The optimal cutoff score at 6 months was between 9 and 10, at which the
      positive predictive value was 89.4, sensitivity was 87.1, and specificity was
      97.8. The optimal cutoff score at 12 months was between 3 and 4, at which the
      positive predictive value was 91.0, sensitivity was 91.5, and specificity was
      97.9. CONCLUSIONS: The EMPP offers the clinician an effective instrument to
      identify children in the first year of life who are at greatest risk for the
      development of CP. The EMPP can be incorporated into a routine health maintenance
      visit, adding only a few minutes to the process, and has high sensitivity and
      specificity.

PMID- 8885949
TI  - Acute response to inhaled nitric oxide in newborns with respiratory failure and
      pulmonary hypertension.
AB  - OBJECTIVE: Systemic oxygenation is improved by inhaled nitric oxide therapy in
      some newborns with respiratory failure and pulmonary hypertension. Our results
      with inhaled nitric oxide were reviewed to determine factors associated with an
      acute improvement in systemic oxygenation. METHODS: Newborns with oxygenation
      indices of 25 to 40 were prospectively randomized to receive conventional therapy
      with or without 20 ppm inhaled nitric oxide. All newborns with oxygenation
      indices greater than 40 were treated with inhaled nitric oxide. Hemodynamic,
      blood gas, and Doppler ultrasound measurements were performed before and after 30
      to 60 minutes of observation or therapy. The severity of lung disease was
      classified by the chest radiograph as: (1) normal or focal disease; (2) moderate
      diffuse disease-diffuse lung disease with well-defined heart borders; or (3)
      severe diffuse disease-diffuse lung opacification with indistinct heart borders.
      RESULTS: Heart rate, blood pressure, and ductal diameters did not change. Blood
      gases and ductal shunting acutely improved only in patients treated with inhaled
      nitric oxide. Patients with normal lung fields or focal disease had the greatest
      degree of improvement in systemic oxygenation. Changes in oxygenation were not
      influenced by gestational age, baseline blood gases, the proportion of right-to
      left ductal shunting, prior treatment with a surfactant, or the use of
      conventional or high-frequency jet ventilation. Collectively, blood gases and
      ductal shunting did not improve with inhaled nitric oxide in patients with lung
      hypoplasia or severe diffuse lung disease. Sustained improvement in oxygenation
      occurred in 87% of patients with oxygenation indices greater than 40 in whom
      oxygenation indices less than 40 acutely developed after exposure to nitric
      oxide, whereas 90% of patients in whom oxygenation indices less than 40 did not
      acutely develop were treated with extracorporeal membrane oxygenation or
      ultimately died. CONCLUSIONS: Inhaled nitric oxide acutely improves systemic
      oxygenation in many newborns with respiratory failure and pulmonary hypertension.
      The diagnosis and chest radiograph are helpful in identifying patients who will
      have favorable acute responses to therapy. In patients with severe hypoxemia, the
      need for invasive support with extracorporeal membrane oxygenation may be
      determined by an acute trial of inhaled nitric oxide.

PMID- 8885950
TI  - Four patterns of response to inhaled nitric oxide for persistent pulmonary
      hypertension of the newborn.
AB  - OBJECTIVE: To determine the clinical role of inhaled nitric oxide (iNO) in the
      treatment of persistent pulmonary hypertension of the newborn (PPHN). STUDY
      DESIGN: Prospective open observational clinical study. SETTING: A regional
      cardiac and pediatric intensive care unit. METHODS: Twenty-five consecutive near
      term neonates (> 35 weeks gestation) with severe PPHN (oxygenation index [OI] >
      25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a
      greater than 20% improvement in PaO2 as well as a decrease in the OI to below 40
      were defined as responders and continued on this therapy. RESULTS: Four patterns
      of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not
      respond to the initial trial of iNO-one survived. Pattern 2 neonates (n = 9)
      responded to the initial trial of iNO, but failed to sustain this response over
      36 hours, as defined by a rise in the OI to > 40. Six survived, five with
      extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the
      initial trial of iNO, sustained this response, and were successfully weaned from
      iNO within 5 days--all survived to discharge. Pattern 4 neonates (n = 3)
      responded to the initial trial of iNO, but developed a sustained dependence on
      iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary
      hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a
      longer period of time than did the sustained responders (pattern 3), but they
      required significantly higher doses of iNO during their first 5 days of iNO
      therapy. CONCLUSIONS: Early responses to iNO may not be sustained. Neonates with
      pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing
      time course of response to iNO when compared with patients who have PPHN in fully
      developed lungs.

PMID- 8885951
TI  - Neurodevelopmental outcome at 36 months' corrected age of preterm infants in the
      Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial.
AB  - OBJECTIVES: Low-dose indomethacin has been shown to prevent intraventricular
      hemorrhage (IVH) in very low birth weight neonates, and long-term
      neurodevelopmental follow-up data are needed to validate this intervention. We
      hypothesized that the early administration of low-dose indomethacin would not be
      associated with adverse cognitive outcome at 36 months' corrected age (CA).
      METHODS: We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6
      to 12 hours in a randomized, prospective trial to determine whether low-dose
      indomethacin would prevent IVH. A priori, neurodevelopmental follow-up
      examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture
      Vocabulary Test-Revised, and standard neurologic examinations were planned at 36
      months' CA. RESULTS: Three hundred eighty-four of the 431 infants survived (192
      [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants
      receiving saline), and 343 (89%) children were examined at 36 months' CA.
      Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167
      infants receiving the placebo were found to have cerebral palsy. There were no
      differences in the incidence of deafness or blindness between the two groups. For
      the 248 English-monolingual children for whom IQ data follow, the mean
      gestational age was significantly younger for the infants who received
      indomethacin than for those who received the placebo. None of the 115 infants who
      received indomethacin was found to have ventriculomegaly on cranial ultrasound at
      term, compared with 5 of 110 infants who received the placebo. The mean +/- SD
      Stanford-Binet IQ score for the 126 English-monolingual children who had received
      indomethacin was 89.6 +/- 18.92, compared with 85.0 +/- 20.79 for the 122 English
      monolingual children who had received the placebo. Although maternal education
      was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no
      difference in educational levels between mothers of the infants receiving
      indomethacin and the placebo. CONCLUSIONS: Indomethacin administered at 6 to 12
      hours as prophylaxis against IVH in very low birth weight infants does not result
      in adverse cognitive or motor outcomes at 36 months' CA.

PMID- 8885952
TI  - Neonatal cranial ultrasound abnormalities in low birth weight infants: relation
      to cognitive outcomes at six years of age.
AB  - OBJECTIVE: To assess the independent relation of neonatal cranial ultrasound (US)
      abnormalities in low birth weight (LBW) infants to cognitive outcomes at 6 years
      of age. DESIGN: Prospective cohort study. SAMPLE AND METHODS: Six-year follow-up
      data were obtained on a regional birth cohort of LBW infants (< 2 kg)
      systematically screened as neonates with serial US. US abnormalities were
      dichotomized into isolated germinal matrix/intraventricular hemorrhage (GM/IVH)
      and parenchymal lesions/ventricular enlargement (PL/VE). Global cognitive
      outcomes (mental retardation, borderline intelligence, and normal intelligence)
      and selected specific cognitive abilities were assessed at 6 years of age with
      standardized instruments. Multivariate techniques were used to assess the effects
      of US independent of maternal social disadvantage at birth and other perinatal
      and neonatal risk factors. RESULTS: The sample as a whole had a significantly
      elevated rate of mental retardation (MR; 5%), almost all moderate to profound in
      severity. PL/VE was independently related to MR (odds ratio [OR], 65.8;
      confidence interval [CI], 19.1 to 22.4) and borderline intelligence (OR, 3.7; CI,
      1.3 to 10.8); isolated GM/IVH was more modestly related to MR (OR, 4.6; CI, 1.2
      to 18.6) but not related to borderline intelligence. Approximately half of the
      cases of MR were attributable to PL/VE independent of other factors. Of non-US
      factors, the number of days receiving mechanical ventilation increased the risk
      for MR. Maternal social disadvantage increased the risk for borderline
      intelligence but not MR. Among children of normal intelligence, those with PL/VE,
      but not isolated GM/IVH, performed more poorly than those without US
      abnormalities on tests of visual perceptual organization but not on tests of
      language, memory, or quantitative skills. CONCLUSION: Prevention of white matter
      injury would substantially improve cognitive outcomes for LBW infants.

PMID- 8885953
TI  - Iodine, thyroid function, and very low birth weight infants.
AB  - OBJECTIVE: Research was undertaken to test two hypotheses. First, during the
      early neonatal period, thyroid function of very low birth weight (VLBW) infants
      is suppressed by exposure to iodine-containing antiseptic solutions and/or
      iodized contrast media. Second, this suppression is more pronounced in small for
      gestational age (SGA) infants. METHODS: Urinary iodine concentration and thyroid
      function measurements were obtained prospectively from 44 VLBW infants with
      gestational ages at birth of 30 +/- 2.3 weeks and weights of 1223 +/- 231 g.
      Eleven of these infants were SGA. The infants were grouped according to iodine
      exposure: 18 infants had no increased exposure and served as control infants; 9
      infants were exposed to an iodine-containing antiseptic (povidone iodine); 12
      infants were exposed to an iodized contrast medium (iopamidol); and 5 infants
      were exposed to both agents. Urinary iodine and serum free triiodothyronine, free
      thyroxine, and thyrotropin were measured on days 1, 7, 14, 21, and 28 of life.
      RESULTS: During the period of maximum exposure (days 1 to 7), the concentration
      of iodine in the urine of study infants was 2 to 4 orders of magnitude greater
      than that in the urine of control infants (123 +/- 141 micrograms/L). During the
      subsequent 3 weeks, levels of urinary iodine in study infants returned to levels
      that were not significantly different from controls. On day 7 of life, iodine
      exposed infants had a significantly higher mean thyrotropin level than control
      infants, whereas on day 28, free triiodothyronine and thyroxine levels were
      lower. Of the 26 iodine-exposed infants, 6 had transient hyperthyrotropinemia and
      2 had transient hypothyroidism. When exposed to iodine, SGA infants had more
      labile thyroid function than normally grown iodine-exposed or control infants.
      These SGA infants had significantly lower levels of thyroid hormones in umbilical
      cord blood, increased production of thyroid hormones on day 14 of life, and lower
      levels again at 1 month. CONCLUSION: In VLBW infants, the use of iodine
      containing antiseptic solutions and iodized contrast media results in massive
      uptake of iodine that is associated with alterations in thyroid function. It is
      reasonable to suggest that, whenever possible, iodized products should be avoided
      in VLBW infants, because their routine use results in exposure to excessive loads
      of iodine, which can be associated with hyperthyrotropinemia and hypothyroidism.

PMID- 8885954
TI  - Prenatal cocaine and neonatal outcome: evaluation of dose-response relationship.
AB  - OBJECTIVE: The aim of this study was to evaluate the hypothesis that prenatal
      cocaine exposure would negatively affect newborn behavior. METHODS: A prospective
      observational study of term infants recruited from the low-risk nursery used a
      structured, standardized interview to obtain maternal data. Cocaine exposure was
      determined by radioimmunoassay of the infant's meconium stool. An examiner
      blinded to the infant's cocaine status administered the Brazelton Neonatal
      Behavioral Assessment Scales. RESULTS: The sample was composed of 23 exposed and
      29 nonexposed infants. On six of the seven Brazelton Neonatal Behavioral
      Assessment Scale clusters, cocaine-exposed infants performed less well than
      control infants, with significant differences observed for autonomic stability.
      In addition, a dose-response relationship was suggested. Significant negative,
      within-group relationships were evident in the exposed group, indicating poorer
      performance with increasing meconium cocaine concentration for orientation (r = 
      .40) and regulation of state (r = -.40). Regression model testing of the
      influence of meconium cocaine concentration on neurobehavioral outcomes, after
      controlling for significant confounders, identified a significant independent,
      negative effect of meconium cocaine concentration on two clusters-motor and
      regulation of state. CONCLUSION: In otherwise healthy full-term infants, prenatal
      cocaine exposure identified by quantitative analysis of cocaine concentration in
      meconium had a significant, independent negative association with motor and
      regulation of state that remained after controlling for other significant
      confounders. A dose-response relationship was evident.

PMID- 8885955
TI  - Chronic pain in cystic fibrosis.
AB  - OBJECTIVE: The objective of this study was to examine the incidence and therapy
      of chronic pain in a group of older patients with cystic fibrosis (CF). PATIENTS:
      We identified two groups of patients followed at the CF Center at Children's
      Hospital (Boston); the first group consisted of all patients above the age of 5
      years who died between 1984 and 1993, and the second was a cohort of 23
      additional CF patients who had been referred to the Pain Treatment Service.
      DESIGN: Medical charts were reviewed for the etiology and therapy of all pain
      episodes requiring medical intervention. RESULTS: The incidence of chronic pain
      in this population increased sharply in the last 6 months of life. Headaches (55%
      of patients) and chest pain (65%) were frequently reported, although back pain
      (19%), abdominal pain (19%), and limb pain (16%) were also reported. In patients
      with headache, the main etiologies were hypercarbia or hypoxia, migraine, and
      sinusitis. The majority of chest pain was musculoskeletal, with pleuritis,
      pneumothorax, and rib fracture also reported as the cause of chest pain.
      INTERVENTIONS: A variety of nonpharmacological and pharmacological therapies were
      reported. Forty-one patients (53%) had pain severe enough to require opioid
      treatment, and 10 patients (13%) received opioids for more than 3 months. In
      eight patients with more severe pain, regional analgesia was found to be
      particularly effective. CONCLUSIONS: Chronic pain is a common problem in CF,
      particularly as the patient population ages. When administered with caution,
      opioids have proven to be effective and safe in this population; regional
      anesthesia can be used to preserve pulmonary toilet while adequately treating
      severe pain.

PMID- 8885956
TI  - Methylphenidate dosing: twice daily versus three times daily.
AB  - OBJECTIVE: To evaluate the short-term efficacy and side effects associated with
      two methylphenidate hydrochloride (MPH) dosing patterns. METHODS: Twenty-five
      boys with attention deficit hyperactivity disorder (ADHD) participated in a 5
      week, triple-blind, placebo-controlled, crossover evaluation of MPH administered
      twice (b.i.d.) versus thrice (t.i.d.) per day (mean dose = 8.8 +/- 5 mg, .30 +/-
      .1 mg/kg/dose). Four dosing conditions (placebo, titration [gradual increase to
      target dose], b.i.d., and t.i.d.) were used. Dependent measures obtained on a
      weekly basis included: parent and teacher ratings of child behavior, parent-child
      conflicts, parent report of stimulant side effects, child self-report of mood
      symptoms, a sleep log, laboratory measures of attention, and actigraphic
      recording of sleep activity. RESULTS: All dosing conditions resulted in
      significant effects on ADHD symptoms when compared with baseline. Relative to
      placebo, t.i.d. dosing was characterized by improvement on the greatest number of
      behavioral measures, and both b.i.d. and t.i.d. were generally more effective
      than titration. Direct comparisons of b.i.d. and t.i.d. dosing revealed that
      t.i.d. was associated with greater improvement on the Conners Parent Rating Scale
      Impulsivity/Hyperactivity factor, with a similar marginally significant effect
      for the ADD-H Teacher Rating Scale Hyperactivity factor. The analysis of
      clinically significant change favored a three-times-a-day dosing schedule over
      placebo on both parent and teacher ratings of impulsivity/hyperactivity and
      attention. Compared with placebo, appetite suppression was rated, on average, as
      more severe in the t.i.d. and titration conditions, but not in the b.i.d.
      condition. However, the number of subjects who exhibited any or severe appetite
      suppression did not differ significantly between the b.i.d. and t.i.d. schedules.
      Although there was no difference in sleep duration for children on b.i.d. and
      t.i.d. schedules, total sleep time appeared to decrease slightly on t.i.d.
      relative to placebo according to both parent ratings and actigraphic assessment.
      There were no significant differences between b.i.d. and t.i.d. on any other side
      effects or sleep variables. CONCLUSIONS: For many children with ADHD, t.i.d.
      dosing may be optimal. There are few differences in acute side effects between
      b.i.d. and t.i.d. MPH dosing. The dosing schedule should be selected according to
      the severity and time course of ADHD symptoms rather than in anticipation of
      dosing schedule-related side effects.

PMID- 8885958
TI  - Predictors of weight loss in children with attention deficit hyperactivity
      disorder treated with stimulant medication.
AB  - OBJECTIVE: A retrospective study was undertaken to examine predictors of weight
      loss in children with attention deficit hyperactivity disorder (ADHD) treated
      with stimulant medication. DESIGN: Children diagnosed with ADHD and treated with
      methylphenidate hydrochloride (MPH) or dextroamphetamine sulfate (DEX) for at
      least 5 months were identified by retrospective chart review. Analyses were
      performed on 32 children (29 boys) treated with MPH and 28 children (25 boys)
      treated with DEX. Variables examined included pretreatment weight, pretreatment
      body mass index (BMI), duration of treatment, total daily dose, and weight
      adjusted dose. RESULTS: The MPH-treated group was initially seen at a mean age
      (+/- standard deviation) of 7.5 years (+/- 2.1). Mean duration of follow-up was
      11.2 months (+/- 3.8). Mean total daily dose was 25.5 mg (+/- 8.2) and mean
      weight-adjusted dose was 1.0 mg/kg/day (+/- .5). Mean change in weight as
      expressed in z scores was -0.4 SD (+/- .7). The DEX-treated group was initially
      seen at a mean age of 9.3 years (+/- 2.7). Mean duration of follow-up was 10.8
      months (+/- 4.1). Mean total daily dose was 14.9 mg (+/- 8.2) and mean weight
      adjusted dose was .5 mg/kg/day (+/- .3). Mean change in weight was -0.6 SD (+/-
      .6). Although the MPH group was younger than the DEX group, there were no between
      group differences in weight or height either before treatment or at follow-up
      when adjusted for age and gender. Using linear regression analysis, significant
      correlations were found between pretreatment weight and change in weight for both
      the MPH-treated group (r = .63) and the DEX-treated group (r = .47). Stepwise
      multiple-regression analysis indicated that pretreatment age, weight-adjusted
      dose, and duration of follow-up did not significantly contribute to the variance
      in change of weight for either the MPH- or DEX-treated groups. To adjust for
      height, changes in BMI were also analyzed. For both medication groups, no
      differences were found between the heavier (BMI > or = 50%) and thinner (BMI <
      50%) children in duration of follow-up, total daily dose, or weight-adjusted
      dose. When the medication groups were combined, a greater proportion of heavier
      children experienced a decrease relative to their predicted BMI compared with
      thinner children (80% vs 52%). Comparisons of mean BMI slopes revealed that the
      heavier group experienced an absolute decrease in their BMI (-.139) in contrast
      to the thinner group (+.014) (t = 2.70). CONCLUSIONS: Pretreatment weight,
      adjusted for age, gender, and height, is a significant predictor of weight loss
      in children with ADHD treated with either MPH or DEX. In contrast, pretreatment
      age, duration of treatment, and weight-adjusted dose were not found to be
      significant predictors.

PMID- 8885957
TI  - Apolipoprotein E polymorphism and serum lipids in a randomized, prospective trial
      of an infant diet with reduced saturated fat and cholesterol.
AB  - BACKGROUND: The inherited apolipoprotein E (apoE) phenotype may determine
      effectiveness of dietary atherosclerosis prevention. This study analyzes the
      effects of apoE phenotypes on changes in serum lipid concentrations in a 6-month
      prospective, randomized trial of a low-saturated-fat, low-cholesterol diet in
      infancy. PATIENTS AND METHODS: One thousand sixty-two healthy infants were
      randomized to intervention and control groups at the age of 7 months. Counseling
      was provided to the intervention families when the children's ages were 7, 8, and
      10 months. Dietary goals were the child's intake of energy ad libitum, fat at 30%
      to 35% of energy, cholesterol at less than 200 mg/d, and saturated,
      monounsaturated, and polyunsaturated fatty acids at a 1:1:1 ratio. Control
      families consumed an unrestricted diet. The apoE phenotype of 846 of the infants
      was determined; serum lipid and lipoprotein concentrations were measured at 7 and
      13 months of age; and nutrient intakes were analyzed using 3-day food records at
      8 and 13 months of age. RESULTS: At 7 months of age, serum cholesterol
      concentration was higher in apoE4-positive infants (E2/E4, E3/E4, and homozygous
      E4) than in apoE4-negative infants (159 +/- 31 mg/dL [4.10 +/- 0.81 mmol/L] vs
      150 +/- 29 mg/dL [3.89 +/- 0.74 mmol/L]). The high-density lipoprotein
      cholesterol concentration was slightly lower in apoE4-positive infants than in
      apoE4-negative infants (34 +/- 8 mg/dL [0.88 +/- 0.20 mmol/L] vs 35 +/- 7 mg/dL
      [0.91 +/- 0.19 mmol/L]). Between 7 and 13 months of age, the serum cholesterol
      concentration in infants in the intervention group was unchanged, apoB
      concentration increased slightly, and apoA1 concentration decreased. In the
      control infants, serum cholesterol concentration increased 9 +/- 25 mg/dL (0.24
      +/- 0.65 mmol/L), apoB concentration increased markedly, and apoA1 concentration
      was stable. Changes in serum lipid and apo concentrations that resulted from the
      dietary intervention were independent of the apoE phenotype. CONCLUSIONS: The
      apoE phenotype influenced serum cholesterol concentration markedly by 7 months of
      age. Between the ages of 7 and 13 months, a reduced saturated fat and cholesterol
      diet effectively prevented the age-associated increases in serum cholesterol and
      non-high-density cholesterol concentrations that were obvious in the control
      infants. The effects of the diet occurred in the infants independently of the
      apoE phenotype.

PMID- 8885959
TI  - Automatic garage door openers: hazard for children.
AB  - OBJECTIVES: Despite significant advances in automatic garage door opener design,
      automatic garage door openers continue to severely injure or kill children. In
      this investigation, we sought to determine the frequency and circumstances of
      accidents that have caused severe injury or death to children. We also tried to
      develop a means by which homeowners can evaluate their door openers. METHODS: We
      present the histories of three children severely injured or killed by automatic
      garage door openers. We reviewed national data of similar accidents primarily
      published by the US Product Safety Commission and Underwriters Laboratories.
      Also, we evaluated 50 automatic door openers for safety of operation. The
      reversing mechanisms of door openers were tested using a cardiopulmonary
      resuscitation mannequin, a roll of paper towels, and a block of wood. RESULTS: In
      the United States, at least 85 children have had permanent brain injury or have
      died since 1974 as a result of accidents involving automatic door openers. A
      review of circumstances of the accidents illustrates that accidents are caused
      both by use of the openers by children and by faults in design. Most accidents
      have occurred when children have found access to the activation devices and have
      been entrapped under closing doors that failed to reverse. However, in one case,
      an adult activated the opener and left the premises before the door completely
      closed. Our evaluation of 50 garage door openers showed that although 88% percent
      reversed when encountering a block of wood, 40% failed to reverse when coming
      down on a supine, child-sized cardiopulmonary resuscitation mannequin.
      CONCLUSIONS: Automatic garage door openers pose a serious risk of severe injury
      or death to children. It is probable that many doors would not reverse if they
      came down on a young child. Therefore, we have devised a way for homeowners to
      test their door openers that closely mimics our evaluations using the mannequin
      by using a large roll of paper towels. If the door fails to reverse using this
      test, we suggest that homeowners disconnect their openers and operate the doors
      manually until the openers are serviced or replace their automatic openers with
      one that meets the latest Underwriters Laboratory standards. We also have other
      recommendations regarding the safe operation of the doors, including improving
      the safety standards for openers in apartment complexes. Compliance with these
      recommendations should reduce the number of injuries to children caused by garage
      door openers.

PMID- 8885960
TI  - Idiopathic disseminated bacillus Calmette-Guerin infection: a French national
      retrospective study.
AB  - OBJECTIVE: Disseminated bacillus Calmette-Guerin (BCG) infection after
      inoculation of live vaccine is considered to result from impaired immunity of the
      child. However, in half of the cases, regarded as idiopathic, no well-defined
      immunodeficiency condition can account for the infection. The objective of the
      present study is to report the prevalence, clinical features, associated
      infections, and outcomes of children with idiopathic disseminated BCG infection.
      DESIGN: National retrospective survey during the period from 1974 through 1994 in
      France. SETTING: All neonatology and pediatrics units in primary care and
      referral centers throughout France. PATIENTS: Data were collected from 595 (82%)
      of 721 units, 377 (93%) of 407 centers, and 320 (93%) of 345 cities. Selection
      criteria included BCG infection, dissemination to at least two areas beyond the
      inoculation site, and no well-defined immunodeficiency condition. Sixteen
      children (8 girls and 8 boys), born to families unrelated to each other but often
      consanguinous (5 of 16) or abroad (5 of 16). RESULTS: The minimal prevalence rate
      was estimated at 0.59 cases per 1 million vaccinated children born in France.
      Clinical features included fever and cachexia, disseminated BCG infection to
      lymph nodes (15 of 16), skin (13 of 16), soft tissues (11 of 16), lungs (11 of
      16), spleen (11 of 16), liver (11 of 16), and bones (9 of 16). Eight children had
      associated or subsequent severe opportunistic infection (50%), with either
      nontyphi Salmonella enterica serotypes (7 of 16) or Mycobacterium abscessus (1 of
      16). The outcome was poor: 8 children (50%) died; the cause of death was BCG
      infection for most children (7 of 8); 8 survived until the last follow-up (50%).
      CONCLUSIONS: Idiopathic disseminated BCG infection is a rare but severe
      complication of BCG vaccination. The infection probably results from an as yet
      unknown genetically determined immunodeficiency condition that affects the
      killing of intracellular bacteria such as BCG and Salmonella.

PMID- 8885961
TI  - Eliminating sleep-associated hypoxemia improves growth in infants with
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: Infants with bronchopulmonary dysplasia (BPD) have been previously
      reported to have a decrease in growth velocity after stopping supplemental oxygen
      (SO). SO was stopped after a short-term recording (20-30 minutes) of pulse oxygen
      saturation (Sao2) of 92% or greater in room air. Other studies have documented
      that Sao2 decreases further during feedings and sleep in infants with BPD. Two
      questions were asked: (1) whether short-term, awake Sao2 studies would reliably
      predict prolonged sleep Sao2; and (2) how Sao2 sustained at 88% to 91% vs 92% or
      greater in room air would impact growth velocity in infants with BPD.
      METHODOLOGY: Short-term Sao2 studies were prospectively compared with prolonged
      sleep Sao2 (n = 63) and the growth velocity of infants who had SO discontinued
      after a prolonged sleep Sao2 recording of 88% to 91% (group 1; n = 14) versus 92%
      or greater (group 2; n = 34) in room air. RESULTS: Failure to maintain Sao2 at
      predetermined levels occurred in 18 (29%) of 63 infants during their first
      prolonged sleep study. There was no correlation between short-term awake Sao2 and
      prolonged sleep Sao2 recordings (r = .02). Body weight, height, weight for
      height, and rate of weight gain were similar for all study infants before SO was
      stopped and remained constant for group 2 infants after SO was stopped. However,
      group 1 infants had a significant decrease in the rate of weight gain (17.3 +/-
      13.1 vs 3.7 +/- 6.1 g/kg per day), and the mean z scores for weight gain and
      weight for height also decreased significantly for group 1 infants. Energy
      intake, incidence of acute infection, hematocrit values, and medication use did
      not differ before or after stopping SO in either group. CONCLUSIONS: This study
      indicated that short-term, awake Sao2 measurements do not predict prolonged sleep
      Sao2, and overall, infants with BPD continued a positive growth trend when Sao2,
      remained greater than 92% during prolonged sleep.

PMID- 8885962
TI  - Routine indomethacin prophylaxis: has the time come?

PMID- 8885963
TI  - The role of the primary care pediatrician in the management of high-risk newborn
      infants. American Academy of Pediatrics. Committee on Practice and Ambulatory
      Medicine and Committee on Fetus and Newborn.
AB  - Quality care for high-risk newborns can best be provided by coordinating the
      efforts of the primary care pediatrician and the neonatologist. This ideally
      occurs in the newborn period, during the critical care and convalescing periods,
      and through the time of discharge. This statement offers guidelines for the
      primary care pediatrician involved in providing neonatal care, and discusses
      his/her individual and shared responsibilities, roles, and relationships with the
      neonatologist and the neonatal intensive care unit.

PMID- 8885964
TI  - Health needs of homeless children and families. American Academy of Pediatrics,
      Committee on Community Health Services.
AB  - The intent of this statement is to substantiate the existence of homelessness in
      virtually every community, illustrate the pervasive health and psychosocial
      problems facing the growing population of children who are homeless, and
      encourage practitioners to include homeless children in their health care
      delivery practices, social services, and advocacy efforts. The recommendations
      will guide practitioners in taking actions to diminish the severe negative impact
      that living in temporary shelters has on the health and well-being of developing
      children. In this statement the American Academy of Pediatrics reaffirms its
      stance that homeless children need permanent dwellings in order to thrive.

PMID- 8885965
TI  - Liability and managed care. American Academy of Pediatrics, Committee on Medical
      Liability.
AB  - This statement is intended to inform practitioners of the liability issues
      arising from managed care arrangements. Although it is not possible for
      pediatricians to completely insulate themselves from all liability in these
      areas, this statement offers a number of strategies to decrease the chances of
      being successfully sued. However, because case law within this realm is
      constantly evolving in each state, these serve only as guidelines and are subject
      to both local and emerging developments.

PMID- 8885966
TI  - The new immunization debate.

PMID- 8885967
TI  - The new immunization debate.

PMID- 8885968
TI  - The new immunization debate.

PMID- 8885969
TI  - Air pollution and sudden infant death syndrome.

PMID- 8885970
TI  - Urine latex agglutination tests.

PMID- 8885971
TI  - Early dexamethasone therapy in very low birth weight infants.

PMID- 8885972
TI  - Acellular pertussis trial.

PMID- 8885973
TI  - Asthma: too much diagnosis and too much medicine.

PMID- 8885974
TI  - "It takes a whole village": working with community coalitions to promote positive
      parenting and strengthen families.

PMID- 8885975
TI  - Spanking and triage.

PMID- 8885976
TI  - Advising parents on discipline: what works.

PMID- 8885977
TI  - What clinicians want to know about teaching families new disciplinary tools.

PMID- 8885978
TI  - Using research to change public policy: reflections on 20 years of effort to
      eliminate corporal punishment in schools.
AB  - In the past 20 years, over half of the states have abolished corporal punishment
      in schools. Without the use of ethically questionable, experimental studies in
      which students were randomly assigned to paddlings, advocacy researchers were
      able to integrate the literature and experimental research on reward, punishment,
      and motivation, and conduct enough studies to provide sufficient data for policy
      changes. Further, every popular school discipline training program promotes well
      proven positive and preventive techniques and punishments that do not inflict
      physical pain. Research on alternatives, naturalistic evidence from schools that
      eliminated corporal punishment, and survey research prove that schools do not
      need to use corporal punishment. The movement to eliminate parental spanking is
      at a stage similar to the beginning of the school corporal punishment debate in
      1976. Even though some studies may show that moderate parental spanking may do no
      short-term harm, there is little scientific evidence that it is necessary. There
      are no data to indicate that schools which eliminated corporal punishment became
      any worse. The same demographic factors and political polarizations that have
      kept about half of American school children from the protections against paddling
      afforded students in almost all other Western democracies also impede the
      movement to eliminate parental spanking. Since we know that corporal punishment
      too often leads to excesses, and since we have a multitude of effective positive
      approaches, what is the worst thing that would happen if all Americans stopped
      hitting children in any setting? The same children who are hit for misbehavior
      would continue that misbehavior and other ineffective punishments would be used.
      Most parents and teachers would discover what behavioral scientists already know.
      A combination of reward, positive motivational techniques and appropriate,
      nonphysical punishments would prevent most misbehavior. Other factors being
      equal, in the next generation, rates of childhood aggression and child abuse
      would drop dramatically, since corporal punishment would not be considered a
      viable and automatic reaction to misbehavior. Not a bad result for giving up
      something that has never been supported by the majority of those who study
      discipline in homes and schools. This is the message researchers and
      practitioners should actively convey to parents, policy makers and the media.

PMID- 8885979
TI  - Research and public policy.

PMID- 8885980
TI  - A review of the outcomes of parental use of nonabusive or customary physical
      punishment.

PMID- 8885981
TI  - A blanket injunction against disciplinary use of spanking is not warranted by the
      data.

PMID- 8885982
TI  - Unintended consequences of punishment.

PMID- 8885983
TI  - How can generative theories of the effects of punishment be tested?

PMID- 8885984
TI  - Spanking and the making of a violent society.

PMID- 8885985
TI  - Assessing the causal effect of childhood corporal punishment on adult violent
      behavior: methodological challenges.

PMID- 8885986
TI  - Subabusive violence in child rearing in middle-class American families.

PMID- 8885987
TI  - The medium/the message: corporal punishment, an empirical critique.

PMID- 8885988
TI  - Cloning and tissue expression of the rat RAB 3C GTP-binding protein.
AB  - A cDNA clone which encodes the low molecular weight GTP-binding protein rab 3C
      was isolated from a rat PC12 pheochromocytoma library. The 1.0 kb clone contains
      the entire coding region (681 bp), as well as 5' (89 bp) and 3' (230 bp)
      untranslated sequences. The predicted amino acid sequence of the rat rab 3C clone
      is 98% identical to the bovine rab 3C sequence and 85% identical to the rat rab
      3A sequence. Northern blot analyses using probes containing coding and noncoding
      sequences of the rat rab 3C clone hybridized to a 9.5 kb transcript in brain,
      adrenal gland, and pituitary RNA pools.

PMID- 8885989
TI  - Calmodulin decreases the estrogen binding capacity of the estrogen receptor.
AB  - We previously demonstrated the ability of calmodulin (CaM) to decrease the
      binding affinity of estradiol (E2) to the rat uterine estrogen receptor (ER). We
      show now that CaM induces a loss of E2 binding capacity especially when ER
      molecules exhibit a lower binding affinity for the hormone. By Western blotting
      and [125I]tamoxifen aziridine covalent labeling we found that this CaM-induced
      loss is not associated with a disappearance of the ER protein. In addition, we
      were able to demonstrate a CaM-mediated decrease in E2 binding of a human
      recombinant ER expressing solely its hormone binding domain (HBD, aa 282-595).
      Hence, CaM can modulate the structure of the HBD of the ER without any
      involvement of a degradative process, this conformational change is not mediated
      by other domains of the receptor and/or components of the native ER
      heterocomplex.

PMID- 8885990
TI  - Granzyme B/perforin-mediated apoptosis of Jurkat cells results in cleavage of
      poly(ADP-ribose) polymerase to the 89-kDa apoptotic fragment and less abundant 64
      kDa fragment.
AB  - Cytotoxic lymphocytes utilize granule associated serine proteases (granzymes) and
      perforin to induce apoptosis. Although the importance of granzyme B has been
      established by gene ablation experiments, biochemical events initiated by the
      granzyme remain enigmatic. We show here that exposure of Jurkat cells to granzyme
      B and perforin results in cleavage of poly(ADP-ribose) polymerase to an apoptotic
      89 kDa fragment and to lesser amounts of a 64 kDa fragment. The 64 kDa fragment
      is produced directly by granzyme B while the 89 kDa fragment is presumably
      generated by activated ICE/Ced-3 proteases. Establishing the intracellular
      function of GrB in the apoptotic response, these results indicate that granzyme B
      enters perforin treated targets activating the ICE/Ced-3 family proteases which
      then cleave poly(ADP-ribose) polymerase to its apoptotic fragment. Intracellular
      granzyme B appears to be translocated to the nucleus where the protease directly
      cleaves poly(ADP-ribose) polymerase.

PMID- 8885991
TI  - Efficient gene transfer to EGF receptor overexpressing cancer cells by means of
      EGF-labeled cationic liposomes.
AB  - Epidermal growth factor (EGF)-labeled cationic liposomes (EGF-liposomes) were
      prepared for efficient gene transfer vector to EGF receptor expressing cells.
      Transfection activity of EGF-liposomes associating plasmid PGV-C which encodes
      luciferase showed a 2-fold increase in EGF receptor expressing cells, HEC-1-A,
      compared to that of EGF-non-labeled liposomes (N-liposomes). In EGF receptor
      deficient HRA cells, however, both EGF- and N-liposomes exhibited low
      transfection efficiency and no difference was observed between them. Furthermore,
      by the addition of anti EGF receptor antibody, transfection efficiency of EGF
      liposomes was suppressed, suggesting EGF receptor-mediated endocytosis of EGF
      liposomes. Transfection activity of EGF-liposomes was strongly dependent on the
      concentrations of fusogenic lipid, dioleoylphospha-tidylethanolamine in
      liposomes. By X-gal staining 6-8% of GCH-1(m) cells which also had EGF receptor
      expressed beta-galactosidase activity following the transfection by EGF-liposomes
      associating pSV-beta-galactosidase. These findings indicate that EGF-liposomes
      could be a preferable vector for EGF-receptor expressing cells.

PMID- 8885992
TI  - Atypical isoforms of pKc and insulin secretion from pancreatic beta-cells:
      evidence using Go 6976 and Ro 31-8220 as Pkc inhibitors.
AB  - The involvement of protein kinase C (PKC) isoforms in glucose-induced insulin
      secretion was investigated by comparing the effects of the PKC inhibitors Go
      6976, which is PKC specific and selective for the Ca(2+)-dependent isoforms, and
      Ro 31-8220, a specific PKC inhibitor which does not discriminate between
      isoforms. Go 6976 inhibited the Ca(2+)- and diacylglycerol (DAG)-dependent PKC
      activities in beta-cell extracts in vitro and fully inhibited insulin secretory
      responses of rat islets of Langerhans to the PKC activator 4 beta phorbol
      myristate acetate (PMA), suggesting that it was an effective inhibitor of the DAG
      dependent isoforms of PKC in situ. However, glucose-induced insulin secretion
      from rat islets was not inhibited by Go 6976, whereas secretory responses to
      glucose were partially inhibited by the non-isoform selective PKC inhibitor, Ro
      31-8220. The simplest explanation of these results is that glucose-induced
      insulin secretion is dependent, at least in part, upon the activation of an
      atypical isoform(s) of PKC within the beta-cell.

PMID- 8885993
TI  - Ongoing activity of RNA polymerase II precludes chromatin collapse and DNA
      fragmentation in Chinese hamster ovary cells.
AB  - The role of ongoing RNA synthesis in chromatin organization in Chinese hamster
      ovary cells was examined upon exposure to the transcription inhibitor alpha
      amanitin. Treatment with alpha-amanitin led to pleomorphic nuclei with chromatin
      heavily condensed and with the remaining ribonucleoprotein aggregated in large
      compact granular masses around the margins of the nuclear periphery. Concommitant
      with the changes in nuclei morphology transient focal dilatation of the rough
      endoplasmic reticulum was observed while other cytoplasmic organelles appeared
      structurally unaffected. The morphological changes occurred after complete
      inhibition of RNA polymerase II mediated transcription. The molecular integrity
      of isolated DNA was monitored in parallel with the structural analysis.
      Fragmentation of cellular DNA occurred in a time-dependent fashion and well after
      the complete inhibition of RNA synthesis. Characteristic oligonucleosomesized DNA
      fragments of about 187 base pairs in length was produced in a cotemporal time
      dependent fashion. Our findings indicate that ongoing transcription and the
      structural state of chromatin are very closely integrated, and provide further
      evidence that RNA is a structural component of the nuclear matrix, which in turn
      is involved in keeping chromatin physically dispersed and decondensed.

PMID- 8885994
TI  - Lactacystin increases LDL receptor level on HepG2 cells.
AB  - Low density lipoprotein (LDL) receptor expression is regulated by proteolysis of
      transcription factors, sterol regulatory element binding proteins. To investigate
      the involvement of proteasome in this regulatory process, the effect of
      lactacystin, a specific proteasome inhibiton of microbial origin, was tested on
      LDL receptor expression on HepG2 cells. The addition of lactacystin to the cell
      culture increased the number of LDL receptors, indicating that proteasome plays a
      down-regulatory role in LDL receptor expression.

PMID- 8885995
TI  - Solid-phase synthesis of caged peptides using tyrosine modified with a
      photocleavable protecting group: application to the synthesis of caged
      neuropeptide Y.
AB  - A simple method for the synthesis of caged peptides using a novel derivative of
      tyrosine, N-Fmoc-O-(2-nitrobenzyl)-tyrosine, is described. The derivative of
      tyrosine can be incorporated at any position in an amino acid sequence by solid
      phase peptide synthesis under the condition for Fmoc chemistry, and caged
      peptides that contain nitrobenzyl group on the side chain of tyrosine residue can
      be obtained. The nitrobenzyl group can be photocleaved by UV irradiation and the
      half life of the intermediate during photolysis is approximately 7 microseconds.
      The method was successfully applied to the synthesis of caged neuropeptide Y
      (NPY). The binding affinity of the caged NPY for the Y1 receptor was one or two
      orders of magnitude lower than that of intact NPY, but it increased to the value
      for intact NPY upon irradiation by UV light.

PMID- 8885996
TI  - Endothelin-1 induces insulin resistance in conscious rats.
AB  - Since endothelin-1 (ET-1) might regulate insulin secretion and glucose
      metabolism, we carried out experiments to study the effect of ET-1 in conscious
      rats by injecting ET-1 (0.5 or 1.0 microgram/100 g body weight, i.p.) and
      examining the plasma glucose (PG) and insulin (PI) concentrations and PG/PI
      ratios continuously for 3 hours after the injection. Compared to the saline
      controls, ET-1 increased PG and PG/ P1 ratios in a dose-dependent manner. Oral
      glucose tolerance test (OGTT) performed at 30 min after the injection showed that
      PG levels stayed significantly higher in rats preinjected with ET-1 than rats
      with saline injection, although the change in PI levels was not different.
      Simultaneous infusion of glucose and insulin to somatostatin-primed rats with ET
      1 or saline injection resulted in significantly higher steady state plasma
      glucose (SSPG) levels and SSPG/PI ratios in rats injected with ET-1 than control
      rats with saline. These results unequivocally indicated that intraperitoneally
      administered ET-1 induces insulin resistance in conscious rats.

PMID- 8885997
TI  - Biochemical characterization of calsequestrin-binding 30-kDa protein in
      sarcoplasmic reticulum of skeletal muscle.
AB  - Calsequestrin (CSQ)-binding 30-kDa protein in the sarcoplasmic reticulum (SR) of
      rabbit skeletal muscle was purified from the junctional face membrane (JFM) in
      the SR. Analysis of proteins which bound to the affinity column conjugated with
      the purified 30-kDa protein was performed. As a result, in the heavy fraction of
      the SR (HSR), four proteins including CSQ proved to be adsorbed on the column,
      and in the JFM, one protein, whose molecular weight was about 25-kDa. was mainly
      adsorbed. Furthermore, the same 25-kDa protein was found to be adsorbed on the
      CSQ affinity column. This 25-kDa protein is probably the CSQ-binding 26-kDa
      protein (junctin) recently reported [Jones, L. R., et al. (1995) J. Biol. Chem.
      270, 30787] judging from the molecular weight and the CSQ-binding property. These
      results suggest that three proteins, CSQ, 30-kDa protein, and 25-kDa protein,
      form a protein complex in the terminal cisternae of the SR.

PMID- 8885998
TI  - An enhanced green fluorescent protein allows sensitive detection of gene transfer
      in mammalian cells.
AB  - The green fluorescent protein (GFP) from the jellyfish Aequorea victoria has
      become an important marker of gene expression. However, the sensitivity of wild
      type GFP has been below that of standard reporter proteins, such as beta
      galactosidase, which utilize enzymatic amplification. To improve the detection of
      GFP in transfected mammalian cells, we have constructed a unique GFP variant
      which contains chromophore mutations that make the protein 35 times brighter than
      wild-type GFP, and is codon-optimized for higher expression in mammalian cells.
      These changes in the GFP coding sequence provide an enhanced GFP (EGFP) that
      greatly increases the sensitivity of the reporter protein. We show that the EGFP
      expression vector delivered into mammalian cells gives rise to bright
      fluorescence that is readily detectable following a 16-24 hr transfection
      interval. Visual detection of transfected cells with EGFP appears to be more
      sensitive than equivalent measurements with beta-galactosidase catalyzed
      conversion of the X-gal substrate. We conclude that EGFP allows sensitive and
      convenient detection of gene transfer in mammalian cells.

PMID- 8885999
TI  - Structure-function studies on synthetic peptides derived from the 109-118 lectin
      domain of selectins.
AB  - Previously, we identified several peptides corresponding to amino acid sequences
      within the lectin domains of selectins that inhibit neutrophil (PMN) adhesion to
      P-selectin. Here we focused on one of the active regions, 109-118, which contains
      residues that have been identified as critical for E-selectin binding to the
      sialyl Lexis X (sLex) counter receptor. Analogues were synthesized and examined
      for their inhibitory effect on PMN binding to P-selectin and E-selectin
      immunoglobulin fusion proteins (P-IgG, E-IgG) and also on P-IgG and E-IgG binding
      to sLex coated surfaces. Peptide sequences which inhibited PMN binding to the
      fusion proteins were not necessarily those that inhibited fusion protein binding
      to sLex. In addition, various amino acid substitutions could be tolerated at the
      111 and 113 positions without altering inhibitory activity. Modeling suggests
      that structural conformations of peptide analogues could explain the differences
      in biological activity of peptide analogues compared to mutants of the native
      protein.

PMID- 8886000
TI  - Application of the ferromagnetic transduction model to D.C. and pulsed magnetic
      fields: effects on epileptogenic tissue and implications for cellular phone
      safety.
AB  - The ferromagnetic transduction model proposed by J.L. Kirschvink (Phys. Rev. A
      (1992) 46, 2178-2184) suggests that the coupling of biogenic magnetic particles
      in the human brain to mechanosensitive membrane ion gates may provide a mechanism
      for interactions of environmental magnetic fields with humans. Extremely low
      frequency alternating magnetic fields primarily were considered, and in the model
      A.C. fields with frequencies below 10 Hz should have minimal effect. We show that
      pulsed fields, square waves, and D.C. fields also could force open the membrane
      gates long enough to disrupt normal neurophysiological processes. The model may
      therefore be extended to explain results obtained in studies of epileptic
      patients which show effects on the central nervous system from low frequency
      square wave and D.C. magnetic fields. In addition, the model also may provide a
      plausible mechanism linking exposure to magnetic fields from discontinuous
      transmission cellular telephones and disruption of normal cellular processes in
      the human brain.

PMID- 8886001
TI  - Dimethyl sulfoxide and related polar compounds enhance infection of human T cells
      with HIV-1 in vitro.
AB  - We observed the enhancing effect of dimethylsulfoxide (DMSO) on infection of
      human T cells with human immunodeficiency virus type 1 (HIV-1). Similar enhancing
      effects were also found in related polar chemicals such as dimethylformamide,
      hexamethylenebisacetamide, sodium butyrate and retinoic acid. In acute infection
      of the human MT-4 T cell line, DMSO at a concentration of 1% reduced the amounts
      of HIV-1 required to establish similar infection by one log. Furthermore,
      infection of peripheral blood lymphocytes with HIV-1 was also augmented several
      times by DMSO. HIV-1 production from persistently infected human T cell lines,
      but not monocytic cell lines, was enhanced by DMSO and related polar chemicals.
      DMSO enhanced transcription of HIV-1 RNA in persistently infected T cell lines,
      and the enhancing effect of DMSO on HIV-1 production was inhibited by
      staurosporine, a protein kinase inhibitor. These findings suggested that DMSO
      enhanced HIV-1 infection of T cells mainly at the step of transcription of viral
      RNA.

PMID- 8886002
TI  - Familial Alzheimer's disease-linked mutations at Val717 of amyloid precursor
      protein are specific for the increased secretion of A beta 42(43).
AB  - In some pedigrees of familial Alzheimer's disease (FAD), three mutations of beta
      amyloid precursor protein (APP) have been found at the Val717 residue (to Ile,
      Phe, or Cly) and these mutations increase the secretion of A beta 42(43). To
      study the specificity of the effects of these mutations on APP processing, we
      transiently expressed APP genes with mutations of Val717 to Lys, Ser, Glu, or Cys
      in COS cells. The three familial AD-linked mutations increased the levels or
      ratios of A beta 42(43), whereas the secretion of A beta 40 was decreased. Other
      mutations irrelevant to FAD except Val717 to Lys had little effect on the ratio
      of A beta 42(43). Substitution to Lys decreased the secretion of A beta 42(43);
      substitution to Glu or Gly decreased the amount of intracellular C-terminal
      fragment produced by alpha-secretase, whereas it was increased by mutations to
      Phe, Cys, or Lys. However, the levels of secretion of soluble APP were constant,
      but a substitution to Glu reduced it. These results suggest a specific role of
      the Val717 residue in APP processing and, especially, in gamma-cleavage.

PMID- 8886003
TI  - Clonal analysis by chromosome 11 microsatellite-PCR of microdissected parathyroid
      tumors from MEN 1 patients.
AB  - Loss of heterozygosity (LOH) at chromosome 11q13 loci has been described in the
      majority of larger parathyroid tumors from patients affected by Multiple
      Endocrine Neoplasia type 1 (MEN 1) syndrome. Since classical histology of the
      whole parathyroid gland does not permit a clear morpho-genetic correlation, the
      clonal composition of abnormal parathyroid tissue was analyzed in DNA obtained
      from single nodules and non-nodular areas within MEN 1 parathyroid lesions.
      Microdissected sections were analyzed by chromosome 11q13 microsatellite-PCR for
      LOH and by patterns of X-inactivation. We detected LOH for chromosome 11q13 loci
      in at least one microdissected area for each familial MEN 1 patient, but not in
      the single sporadic case. X-inactivation pattern of two "clonal" tumors exhibited
      a polyclonal cell composition of these microdissected samples, indicating the
      existence of a genetic heterogeneity in MEN 1 parathyroid microareas exhibiting a
      "clonal" pattern for allelic losses.

PMID- 8886004
TI  - Spatial and temporal Mg2+ signaling in single human tracheal gland cells.
AB  - The combined use of Mag-indo-1 probe and laser confocal UV
      microspectrofluorometry allowed us to investigate the spatial and temporal
      dynamic changes of the Mg2+ variations in human tracheal gland (HTG) cells at the
      single cell level. Stimulation of HTG cells with either bradykinin, ouabain or
      extracellular high Mg2+ concentrations (up to 10 mM) induced increases in
      intracellular Mg2+ concentration [Mg2+]i. From a cytosolic basal concentration of
      0.8 +/- 0.3 mM in a medium free of Mg2+, an increase in extracellular Mg2+
      concentration from 1 to 10 mM, increased cytosolic [Mg2+]i from 1.4 +/- 0.6 to
      1.8 +/- 0.8 mM after 10 min (p < 0.05). We also demonstrated using line-scanned
      spectral images within single cells, that the [Mg2+]i is distributed uniformally
      in the nucleoplasm, but in contrast, showed marked local differences among
      different cytoplasmic regions, thus suggesting a functional heterogeneity in the
      intracellular Mg2+ stores involved. The influx pathway for Mg2+ in HTG cells was
      not inhibited by verapamil and appeared to be independent of [Ca2+]i.

PMID- 8886005
TI  - Expression of rho A and rho kinase mRNAs in porcine vascular smooth muscle.
AB  - It has recently been indicated that rho A and rho kinase may be involved in the
      mechanism for the increase in Ca2+ sensitivity in smooth muscle myofilaments. In
      the present study, we investigated the mRNA expression of rho A and rho kinase in
      porcine vascular smooth muscle cells (aorta, coronary artery, pulmonary artery,
      and pulmonary vein). In reverse transcription-polymerase chain reaction (RT-PCR)
      experiments, using total RNA from these tissue specimens and the primers designed
      in the conserved regions of each mRNA in human and bovine, rho A and rho kinase
      mRNAs were detected in all of these smooth muscle cells. An analysis of these PCR
      products by direct sequencing indicated that they were derived from each mRNA.
      The finding that both rho A and rho kinase mRNAs were expressed in the various
      porcine vascular smooth muscle cells strongly supports the idea that these
      proteins are involved in the mechanism dealing with the increase in Ca2+
      sensitivity in the myofilaments of vascular smooth muscle cells.

PMID- 8886006
TI  - CFTR expression in C127 cells is associated with enhanced cell shrinkage and ATP
      extrusion in Cl(-)-free medium.
AB  - In this study we have employed three lines of C127 murine cells. C127 CFTR w/t,
      C127 CFTR delta F508 and C127 mock, transfected with, respectively, wild type,
      delta F508 mutant human CFTR cDNA or the vector only. In the first 10 minutes of
      a Cl(-)-free incubation the three cell lines exhibit a significant shrinkage due
      to a loss of K+ and Cl-. However, C127 CFTR w/t cells shrink more than C127 CFTR
      delta F508 and the mock cells. The supplementation of Cl(-)-free medium with ATP
      causes a marked decrease in the cell volume of C127 CFTR delta F508 and of the
      mock cells but not of C127 CFTR w/t cells. ATP effect is mimicked by adenosine 5'
      O-(3-thiotriphosphate), but neither by adenosine nor by UTP. Measurements of
      extracellular ATP indicate that during the Cl(-)-free incubation C127 CFTR w/t
      cells extrude more ATP than the other two cell lines. The results are consistent
      with the hypothesis that CFTR enhances K+ and Cl- permeabilities by promoting the
      extrusion of ATP.

PMID- 8886007
TI  - Bacillus subtilis Ffh, a homologue of mammalian SRP54, can intrinsically bind to
      the precursors of secretory proteins.
AB  - We analyzed the binding activity of B. subtilis Ffh to the precursors of
      secretory proteins by purifying mature and precursor proteins of beta-lactamase
      derived from pUC18 and its derivatives, of which the signal peptide region was
      replaced with that of E. coli OmpA, B. subtilis AprE, PBP5* or an alkalophilic
      Bacillus sp. #1011 CGTase. Each of them was mixed with purified B. subtilis Ffh
      in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). The
      tested precursor proteins, including those of E. coli, of which the signal
      sequences differ from those of B. subtilis in the number of charged amino acids
      and hydrophobicity, cross-linked with Ffh, whereas mature proteins did not. The
      addition of scRNA, the B. subtilis counterpart of mammalian SRP 7S RNA, into the
      mixture did not affect the complex formation. These findings suggest that B.
      subtilis Ffh intrinsically binds to several precursor proteins.

PMID- 8886008
TI  - H1-H1 cross-linking efficiency depends on genomic DNA methylation.
AB  - Oligonucleosomal DNA preparations from condensed-inactive chromatin were
      examined, before and after artificial methylation by bacterial SssI methylase,
      for their ability to allow cooperative H1-H1 interactions under conditions of
      different ionic strength. Our results support the conclusion that, within the
      highly methylated genomic DNA, there are some CpG's whose unmethylated state is
      critical for chromatin folding. Circular dichroism spectra indicate that
      artificial overmethylation of native oligonucleosomal DNA reduces its efficiency
      in inducing an ordered conformation of H1 histone. Temperature melting profiles
      confirm on the other hand that the native and the artificially overmethylated
      forms of oligonucleosomal DNA are both able to bind H1 histone.

PMID- 8886009
TI  - The long and the short isoform of cell-CAM 105 show variant-specific
      modifications in adult rat organs.
AB  - The cell adhesion molecule cell-CAM 105 is a member of the carcinoembryonic
      antigen (CEA)-gene family and expressed on the cell surface at least as a long (L
      ) and a short (S-) isoform. We have developed anti-peptide antisera to
      investigate the expression patterns of both cell-CAM 105 variants in rat organs.
      In immunohistochemistry the S- and the L-isoform were co-localized in every
      tissue investigated. In contrast, the quantification of both isoforms in rat
      organs by a sandwich-ELISA revealed several differences in their relative
      expression ratio if compared to the liver value. In submandibular gland and
      seminal vesicle a significant increase of the S-isoform was found, whereas in
      kidney the L-isoform was overexpressed. In immunoblot analysis of kidney and
      seminal vesicle the two isoforms did not appear with the Mr difference which is
      deduced from their primary structures, suggesting that the two cell-CAM 105
      variants are subjected in these tissues to different post translational
      modifications.

PMID- 8886010
TI  - Occurrence of sex steroid hormones and their binding proteins in Octopus vulgaris
      lam.
AB  - The present study reports the presence of progesterone, testosterone and 17 beta
      estradiol and their corresponding binding proteins in the reproductive system of
      Octopus vulgaris Lam (phylum Mollusca, subphylum Cephalopoda). These sex hormones
      occur in testis, vas deferens, seminal vesicle, prostate and Needham's sac. The
      hemolymph also contains a small, but significant, amount of these hormones and
      their carrier proteins. Among various tissues of the reproductive system, the
      seminal vesicle possesses the highest concentration of progesterone (4.8 ng/g
      tissue). The testis is the organ which contains the highest amount of
      testosterone (5.2 ng/g) whereas the prostate is the organ which contains the
      highest amount of 17 beta-estradiol (0.92 ng/g). The presence of these hormones
      has been ascertained by a radioimmunoassay method, an immunoenzymatic method and
      by a chemical (HPLC) method. Seatchard studies indicated that vas deferens and
      seminal vesicle contain specific sex steroid binding molecules at affinity levels
      comparable to those of vertebrate steroid receptors (0.5-5.0 pmol/g protein). In
      addition to the presence of the hormones, the delta 5,3 beta hydroxysteroid
      dehydrogenase, the key enzyme of steroidogenesis, also is found in testis. From a
      phylogenetic point of view, these findings are very interesting because they
      indicate a common origin of a sex hormonal system between Mollusca Cephalopoda
      and Vertebrates.

PMID- 8886011
TI  - Genetic linkage of the sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase II
      gene to intracellular Ca2+ concentration in the spontaneously hypertensive rat.
AB  - A cosegregation analysis of sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase
      (SERCA) II genotype, systolic blood pressure and platelet intracellular Ca2+
      concentration was performed to dissect polygenic hypertensive traits in
      spontaneously hypertensive rats. Backcross analysis between spontaneously
      hypertensive rats and normotensive. Donryu rats demonstrated the existence of an
      inferred single major gene locus (ht). Thrombin-stimulated intraplatelet Ca2+
      concentration was significantly higher in the SERCA II homozygotes than in the
      heterozygotes. The SERCA II genotype did not cosegregate with the blood pressure
      level. The SERCA II gene was assigned to rat chromosome 12. These results suggest
      that the SERCA II gene on rat chromosome 12 contributes to increased thrombin
      stimulated intraplatelet Ca2+ concentration and that the SERCA II gene is not
      identical to ht.

PMID- 8886012
TI  - Repeated peripheral administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin
      alters the binding activities of 5-HT1A and 5-HT2 receptors in rat brain.
AB  - Repeated peripheral administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R
      THBP) induced significant changes in the binding activities of serotonergic
      receptors in the rat brain. The increase in the hippocampus and the decrease in
      the visual cortex of [3H]8-hydroxy-N,N-dipropyl-2-aminotetralin ([3H]8-OH-DPAT)
      binding (5-HT1A binding site) were found to be significant following R-THBP
      administration (20 mg/kg, twice a day for 1 week). [3H]Ketanserin binding (5-HT2
      binding site) was increased in the striatum and hippocampus, whereas it was
      decreased in the cerebellum and visual cortex. Scatchard plot analysis showed ca.
      20% reduction in the Bmax of [3H]8-OH-DPAT and [3H]ketanserin binding in the
      visual cortex, and KD values for [3H]8-OH-DPAT and [3H]ketanserin bindings in the
      hippocampus were significantly reduced 51% and 66%, respectively. These
      differential changes in 5-HT binding might be involved in the central action of R
      THBP.

PMID- 8886013
TI  - Efrapeptins block exocytic but not endocytic trafficking of proteins.
AB  - During the course of screening studies to identify inhibitors of intracellular
      protein trafficking, we isolated efrapeptins as active principles. These
      compounds arrested syncytium formation (SF) and cytopathic effect (CPE) in
      Newcastle disease virus (NDV)- and vesicular stomatitis virus (VSV)-infected BHK
      cells, respectively, without profoundly affecting glycoprotein synthesis.
      Efrapeptins blocked cell surface expression of NDV-HN and VSV-G glycoproteins,
      but did not suppress intoxication by ricin or diphtheria toxin even after
      prolonged pretreatment. Efrapeptins are inhibitors of F-ATPase, or ATP synthase,
      but their inhibitory effect on SF and CPE was independent of the amount of
      intracellular ATP.

PMID- 8886014
TI  - Ser-27, Tyr-10 and Tyr-7 in the alpha-chain of pig stomach H+,K(+)-ATPase as
      Ca(2+)-dependent phosphorylatable sites by intrinsic and extrinsic protein
      kinases.
AB  - When pig stomach membrane H+,K(+)-ATPase preparations were incubated with [gamma
      32P]ATP, Mg2+ and Ca2+, reversible phosphorylation of specific Tyr and Ser
      residues in the N-terminal alpha-chain of H+,K(+)-ATPase occurred without any
      detectable phosphorylation in other regions of the alpha-chain. Mild
      tosylphenylalanyl chloromethyl ketone trypsin treatment followed by reverse-phase
      column chromatography yielded three radioactive peptide peaks. The first peak
      contained both Tyr10(32P) and Tyr7(32P) and the second peak contained Tyr10(32P).
      The third peak contained Ser27(32P) which was also obtained after trypsin
      treatment of partially purified H+,K(+)-ATPase preparations phosphorylated with
      protein kinase-C + Ca2+ or protein kinase-A. This is the first demonstration of
      Ca2(+)-dependent phosphorylation of the alpha-chain of H+,K(+)-ATPase by protein
      kinases.

PMID- 8886015
TI  - Enhancement of superoxide production and protection against heat shock by HSP27
      in fibroblasts.
AB  - Extracellular superoxide production in the Chinese hamster CCL39 fibroblast cell
      line was detected by direct counting of luminol-enhanced chemiluminescence in the
      presence of horseradish peroxidase (HRP). This superoxide production, which is
      directly related to cell density, can be inhibited by diphenylene iodonium, a
      specific inhibitor of NADPH-oxidase. The O2- generation is transiently inhibited
      following exposure of the cells to elevated temperatures. To study the possible
      relationship between HSP27 and its modulation of NADPH-oxidase activity we
      measured the generation of O2- activity in CCL39 cells containing either the gene
      coding for human HSP27 or a mutant form of this gene leading to HSP27 unable to
      be phosphorylated. Cells with the enhanced expression of normal human HSP27 as
      well as the non-phosphorylatable protein exhibited a 20-fold higher superoxide
      production than control CCL39 cells. Furthermore, we demonstrate that
      accumulation of normal HSP27 appears to play a role in prevention of NADPH
      oxidase inhibition by heat.

PMID- 8886016
TI  - Long-term human T-cell culture system supporting hepatitis C virus replication.
AB  - We recently found that human T-cell leukemia virus type I-infected cloned MT-2C
      cells could support the replication of hepatitis C virus (HCV) up to 30 days
      postinoculation (p.i.). To obtain a more persistent HCV replication system using
      MT-2C cells, we examined the effect of various culture conditions after virus
      inoculation. We found that persistent HCV infection (at least 80 days) could be
      reproducibly achieved by reducing the temperature from 37 degrees C to 32 degrees
      C. Under this culture condition, HCV RNA could be detected in the cells up to 198
      days p.i. Sequence analysis of HCV hypervariable region 1 revealed that certain
      HCV species became predominant during the culture period. We also demonstrated
      that virus transmission by the cell-free mode could be successfully repeated at
      least 4 times at 32 degrees C as opposed to only twice at 37 degrees C. This HCV
      infected culture system will be useful for the various biological studies,
      including investigations into the mechanisms of HCV replication and
      multiplication.

PMID- 8886017
TI  - Targeting of liposomes to HIV-1-infected cells by peptides derived from the CD4
      receptor.
AB  - Liposomes can be targeted to HIV-infected cells by either reconstituting
      transmembrane CD4 in the membrane or covalently coupling soluble CD4 to modified
      lipids. We investigated whether synthetic peptides could be used as ligands for
      targeting liposomes. A synthetic peptide from the complementarity determining
      region 2 (CDR-2)-like domain of CD4 could bind specifically to HIV-infected cells
      and mediate the binding of peptide-coupled liposomes to these cells. A peptide
      from the CDR-3-like domain of CD4 inhibited HIV-induced syncytia formation, but
      failed to target liposomes to infected cells. This apparent discrepancy may be
      due to the requirement for a conformational change in the CD4 receptor for the
      CDR-3 region to interact with the HIV envelope protein. Our results demonstrate
      the feasibility of using synthetic peptides to target liposomes containing
      antiviral drugs to HIV-infected cells.

PMID- 8886018
TI  - A test of the hypothesis that ELF magnetic fields affect calcium uptake in rat
      thymocytes in vitro.
AB  - The experiment's objective was to test the statistical hypothesis that a 60-min
      exposure of rat thymocytes in vitro to a unique combination of static and a.c.
      magnetic fields results in suppression of calcium influx triggered by
      concanavalin A (Con A). Con A (10 micrograms/ml) induced about a 50% increase in
      45Ca2+ uptake relative to no Con A (control). Magnetic field exposures had no
      statistically significant effect on Con A-stimulated calcium uptake. The data did
      not support the hypothesis.

PMID- 8886019
TI  - Interaction of organotins with a vacuolar-type H(+)-ATPase.
AB  - Organotin-flavone complexes of 3-hydroxyflavone 3,5,7-trihydroxyflavone
      (galangin) and 2',3,4',5,7-pentahydroxyflavone (morin) are potent inhibitors of
      the vacuolar H(+)-translocating ATPase from bovine adrenal chromaffin granules,
      with K, values around 0.3 microM. The fluorescence of the 3-hydroxyflavone
      complex is enhanced on binding to the purified, reconstituted V-ATPase, and
      tributyltin reduces this fluorescence enhancement, though not strictly
      competitively. Radioiodinated derivatives of galangin and morin were synthesized
      and their organotin complexes were crosslinked to the ATPase by ultraviolet
      irradiation. Subunit A (72 kDa) of the V-ATPase was labelled, and tributyltin
      strongly inhibited this labelling. Subunits M115 and M39 were labelled less
      strongly and tributyltin did not affect this labelling. We conclude that there is
      a specific interaction between organotin compounds and V-ATPase subunit A, in the
      catalytic sector of the enzyme. This approach did not detect the recently
      reported interaction between dibutyltin-3-hydroxyflavone bromide and the 16 kDa
      'proteolipid' subunit of the V-ATPase.

PMID- 8886020
TI  - Molecular cloning and RNA expression of two new human chemokine receptor-like
      genes.
AB  - Two new human genes encoding putative G protein-coupled receptors were cloned
      from genomic DNA following a degenerate PCR strategy. The predicted amino acid
      sequences of the proteins encoded by these genes have the characteristic motifs
      of chemokine receptors. This prompted us to name these genes CKR-L1 and CKR-L3.
      Nevertheless, the identification of their ligands has not been possible using 16
      human chemokines in three different assays. The RNA expression pattern of CKR-L1
      and CKR-L3 is also similar to that generally found for chemokine receptors. To a
      different extent, these genes are expressed in spleen, lymph nodes, and CD4+,
      CD8+ and CD19+ lymphocytes. CKR-L1 expression was also detected in
      monocyte/macrophages. The homology to chemokine receptors suggests that CKR-L1
      belongs to the family of beta chemokine receptors, while CKR-L3 is more similar
      to alpha chemokine receptors.

PMID- 8886021
TI  - Refolding of SDS- and thermally denatured MM-creatine kinase using cyclodextrins.
AB  - We have tried to refold thermally-denatured MM-CK using detergent and
      cyclodextrins as protein folding assistants. This procedure, named artificial
      chaperone-assisted refolding, has been extensively tested to refold carbonic
      anhydrase B. Here, we describe a study which shows that this procedure can be
      applied to refold a dimeric multidomain protein : MM-creatine kinase. The pair
      SDS/hydroxy-propyl beta-cyclodextrin was used in this sequential refolding
      method. In the first step, the protein was denatured by SDS which is able to
      strongly inhibit aggregation. In the second step, hydroxy-propyl beta
      cyclodextrin, an efficient SDS-stripping agent, is added and the denatured enzyme
      can regain its native structure as shown by the 75% reactivation. In conclusion,
      this study suggests that this procedure can be widely used to refold monomeric,
      as well as oligomeric, multidomain proteins.

PMID- 8886022
TI  - In vivo regulation of the IL-1 beta system (ligand, receptors I and II, receptor
      accessory protein, and receptor antagonist) and TNF-alpha mRNAs in specific brain
      regions.
AB  - Interleukin-1 beta (IL-1 beta) acts directly in the central nervous system (CNS).
      Here, using a novel behavioral-molecular approach, we report the regulation of
      the complete II-1 beta system (ligand, receptors, receptor accessory protein, and
      receptor antagonist) and TNF-alpha mRNAs in the CNS in response to the chronic
      intracerebroventricular microinfusion of IL-1 beta. IL-1 beta increased the IL-1
      beta system and TNF-alpha mRNAs in the cerebellum and parieto-frontal cortex. IL
      1 beta-induced profiles of IL-1 beta, IL-1 receptor type I and II (IL-1RI and IL
      1RII), and IL-1 receptor antagonist (II-1Ra) mRNAs were highly intercorrelated in
      the same samples. The data suggest the operation of an IL-1 beta feedback system
      (IL-1 beta/IL-1RI/IL-1RII/IL-1Ra) within a brain region. The fine regulation of
      the CNS IL-1 beta system may depend on a balance between the ligand (IL-1 beta)
      action on the IL-1RI and the induction of inhibitory mechanisms (IL-1RII and IL
      1Ra). This may have implications regarding neurological diseases associated with
      high levels of IL-1 beta in the brain.

PMID- 8886023
TI  - The calcium-independent receptor of alpha-latrotoxin is not a neurexin.
AB  - alpha-Latrotoxin (alpha-LTx), a vertebrate neurotoxin isolated from Black Widow
      Spider venom, causes massive spontaneous neurotransmitter release. The molecular
      mechanism(s) by which the toxin exerts its effect is largely unknown. Here we
      report identification and purification of a novel membrane receptor with high
      affinity for alpha-LTx. Unlike neurexin Ia, a previously described high affinity
      alpha-LTx receptor, this novel protein binds alpha-LTx independently of Ca2+
      presence and therefore may be a mediator of the calcium-independent stimulation
      of neurotransmitter release by alpha-latrotoxin. The major protein component of
      calcium-independent alpha-LTx receptors is a novel M(r) 120,000 protein which
      does not belong to the neurexin family. Among several tissues tested, the M(r)
      120,000 protein was found only in brain.

PMID- 8886024
TI  - Src kinase pathways in extracellular Ca(2+)-dependent pancreatic enzyme
      secretion.
AB  - We investigated the functional roles of Src kinase pathways in rat pancreatic
      acinar cells. CCK-8 dose-dependently increased Src kinase activities by a
      mechanism that was sensitive to herbimycin A. CCK-8 enhanced protein tyrosine
      kinase (PTK) activities when the synthetic Src peptide was used as a substrate.
      Increased PTK activities, sustained Ca2+ entry, and amylase secretion, all
      stimulated by CCK-8, were abolished by eliminating extracellular Ca2+ ([Ca2+]o).
      CCK-8 caused tyrosine phosphorylation of three major proteins: 60 KDa, 85 KDa,
      and 105 KDa. The elimination of [Ca2+]o prevented the tyrosine phosphorylations
      of p60 and p105, but not p85. Therefore, the p60 Src kinase and the p105 kinase,
      referred to as "Src kinase kinase', may be involved in [Ca2+]o-dependent
      pancreatic exocytosis.

PMID- 8886026
TI  - Calpain subunits remain associated during catalysis.
AB  - The Ca2+ dependent cysteine proteases, calpains are heterodimers containing a
      large (ca. 80 kDa) catalytic subunit and a 25-30 kDa small subunit. Whether
      calpains remain dimers while catalyzing hydrolysis of protein substrates has been
      controversial. Now by doing subunit co-immunoprecipitation, we provide direct
      evidence to resolve this argument. In the presence of Ca2+ concentrations which
      permit catalytic activity, both subunits of either m- or mu-calpain are co
      immunoprecipitated by monoclonal antibodies directed against a single subunit.
      Furthermore, both subunits can be co-immunoprecipitated during calpain-catalyzed
      proteolysis of the substrate casein. These results indicate that both major
      calpain isozymes maintain their heterodimeric form during the catalytic cycle.
      Thus, small subunit might have a direct role in regulating the physiologic
      function of either major calpain isozyme.

PMID- 8886025
TI  - Leishmania donovani possess a NADPH-dependent alkylglycerol cleavage enzyme.
AB  - Leishmania parasites possess an abundance of ether-linked hydrocarbons as
      components of phospholipids and glycosylphosphatidylinositol anchors of
      glycoproteins and polysaccharides, including important surface molecules such as
      lipophosphoglycan (LPG) and glycosylinositolphospholipids (GIPLs). Cleavage of
      the ether bond is an important feature in the turnover pathway of alkylglycerols.
      In mammals, ether lipid cleavage activity requires a pteridine cofactor (H4
      biopterin), suggesting the potential for linkage between the unusual Leishmania
      pteridine metabolic pathways and lipid metabolism. In this study, we partially
      purified and characterized an activity in L. donovani capable of cleaving the
      ether lipid 1-O-alkyl[3H]glycol. Unlike the mammalian enzyme but like that of
      Tetrahymena, the Leishmania enzyme required NADPH rather than H4-biopterin. The
      use of divergent cofactors by the parasite and mammalian enzymes may provide a
      basis for the design of anti-parasitic drugs targeting ether-linked lipid
      metabolism.

PMID- 8886027
TI  - The cloning and expression of the baboon acid-labile subunit of the insulin-like
      growth factor binding protein complex.
AB  - The circulating insulin-like growth factors (IGF-I and -II) occur largely as
      components of a 140 kDa protein complex with IGF binding protein-3 and the acid
      labile subunit (ALS). This ternary complex regulates the metabolic effects of the
      serum IGFs by limiting their access to tissue fluids. Since the tissue
      distribution of ALS gene expression has not been reported in humans or other
      primates, and the baboon has been developed as a model for human growth and
      metabolism, it was chosen for this study. A cDNA for baboon ALS was isolated by
      reverse transcriptase polymerase chain reaction and used to screen Northern blots
      of total RNA from the lung, liver, kidney, adrenal, muscle, intestine, and spleen
      of adult baboons. The expression of the single approximately 2.2 kb baboon ALS
      mRNA transcript was restricted to the liver, suggesting that serum ALS levels are
      controlled by regulation of hepatic expression of this peptide in primates.

PMID- 8886028
TI  - Temperature-jump induced fast refolding of cold-unfolded protein.
AB  - Transient protein structures with only microsecond live times may be solved at
      the resolution of single residues by temperature jumping of cold denatured
      protein [Nolting, B., Golbik, R., and Fersht, A. R. (1995) Proc. Natl. Acad. Sci.
      USA 92, 10668-10672]. Here it is shown how this method may be extended to the
      study of intermediates and transition states which are located on the reaction
      coordinate between the main folding transition state and the native state. When
      incubating bovine beta-lactoglobulin A under conditions which favour cold
      unfolding and rapidly refolding the partially cold unfolded protein by a
      temperature jump from -4 to 2 degrees C, a fast folding kinetics with a rate
      constant of about 100 s-1 is observed. The amplitude of the relaxation decays
      following a single exponential function of the time of incubation at low
      temperature before the T-jump. The rate constant of decay matches the rate
      constant of the main unfolding transition, showing that early in the cold
      denaturation reaction, beta-lactoglobulin is kinetically trapped in a partially
      unfolded intermediate state. Despite the only small fluorescence change,
      refolding within about 10 ms after a temperature jump involves a considerable
      degree of solvent exclusion and burial of hydrophobic surface, suggesting a
      contraction of the molecule.

PMID- 8886029
TI  - M-glycogenin, the protein moiety of Neurospora crassa proteoglycogen, is an auto-
      and transglucosylating enzyme.
AB  - Neurospora crassa proteoglycogen was purified and its protein moiety, M
      glycogenin, was released by amylolytic treatment. The released protein was
      capable of autoglucosylation from UDP-glucose forming glucosyl-alpha 1,4-glucosyl
      linkage. The kinetics of autoglucosylation suggested an intramolecular mechanism
      of reaction. M-glycogenin was also able to glucosylate dodecyl-beta-maltoside and
      autoglucosylate, simultaneously and independently. Both auto- and
      transglucosylation reactions were dependent on Mn2+. Thus, M-glycogenin, which
      has also been described as the constituent of Escherichia coli proteoglycogen (A.
      Goldraij and J. A. Curtino. 1993, Biochem. Mol. Biol. Int. 30, 453-458), is a
      glucosyltransferase that bears similar catalytic properties with mammalian
      glycogenin. This is the first report on the enzymatic character of the protein
      constituent of proteoglycogen in primitive organisms, which suggest that the
      mechanism for the de novo biosynthesis of glycogen was conserved over a very long
      period of evolution.

PMID- 8886030
TI  - Cyclic AMP-stimulated accumulation of the cAMP response element binding protein
      can occur without changes in gene expression.
AB  - The cAMP response element binding protein (CREB) is expressed at constitutively
      low levels in most cell types, and the CREB promoter possesses features that are
      typical of house-keeping genes. Since the CREB promoter also contains sequences
      which can mediate cAMP responsiveness in transfection experiments, it has been
      proposed that transcription of the CREB gene is controlled by positive
      autoregulation. In the present study, we show that cAMP does not regulate the
      level of CREB mRNA in any of the tissue-or cell-types that we examined, nor is
      expression regulated by other hormones which commonly affect gene expression.
      However, treatment of rat hepatoma cells with cAMP did result in accumulation of
      CREB protein. We conclude that the positive autoregulation of CREB expression
      which has been proposed is not ubiquitously operational, although CREB protein
      levels can be regulated in a cell-specific manner which does not involve
      transcriptional activation of the CREB gene.

PMID- 8886031
TI  - [Prevention and treatment of solid tumors with retinoids].
AB  - Retinoids regulate terminal differentiation of various cells and morphogenesis of
      various organs. Disorders of such regulations induce cellular and structural
      anomalies, and lead directly to carcinogenesis. According to these physiological
      roles of retinoids, many experimental studies have been conducted to test, and
      successfully demonstrate, the effect of retinoids for the treatment of cancers or
      the prevention of carcinogenesis. In clinical studies, however, retinoid therapy
      has not been established as a first choice treatment for solid tumors, although
      the effect of all-trans retinoic acid for acute promyelocytic leukemia is
      excellent. Primary cancer chemoprevention in general populations using beta
      carotene has failed in all but one of four recently reported trials. In contrast,
      secondary chemoprevention by retinoids is promising for cancers such as head and
      neck cancer, uterine cervical cancer and hepatoma.

PMID- 8886032
TI  - [Surgical treatment of pancreatic cancer and its prognosis-long-term therapeutic
      results after resection].
AB  - A total of 15,731 pancreatic cancer cases were registered by the Pancreatic
      Cancer Registration Committee of the Japan Pancreas Society (JPS) in a period of
      over 14 years. Tumor resection was performed in 35.4% of the total. The five-year
      actuarial survival rate of resected cases was 17.5%. 130 patients histologically
      confirmed had long-term (over 5 years) survival, among whom were only 7 patients
      with n3, pv3, ly3, a3 and pl (+) as histological criteria by JPS. The combined
      use of radiation therapy and chemotherapy after resection for Stage I, Stage II
      and Stage III disease proved effective. According to the National Cancer Data
      Base (NCDB), though the resection rate was only 14.2%, the long-term survival
      rate was similar to that by JPS, because Stage IV disease was only 8% of patients
      who received resection in NCDB's report. Selected patients seemed to be allowed
      to undergo resection. We concluded that it was very important to select patients
      to improve therapeutic results for pancreatic cancer.

PMID- 8886033
TI  - [Adjuvant therapies in combination with pancreatectomy for carcinoma of the
      pancreas].
AB  - In the treatment of adenocarcinoma of the pancreas, surgical resection is the
      only curative strategy. However, the long-term survival rate after pancreatectomy
      remains poor, and most patients died of loco-regional and/or hepatic recurrence.
      Thus, we should perform effective adjuvant therapies in combination with surgery,
      in order to completely prevent these two types of cancer relapse. The present
      article is designed to introduce the recent reports on the adjuvant chemo-and/or
      radio-therapies for this cancer. As for loco-regional control, extended
      pancreatectomy plus chemoradiation seems to be most promising, and preoperative
      chemoradiation will be more popular in the near future. In order to decrease
      hepatic metastasis, our "2-channel chemotherapy", a continuous infusion of 5-FU
      via both hepatic artery and portal vein, is very promising. If postoperative
      survival is improved by combining these two types of regional therapy, the role
      of pancreatectomy will be enlarged and more widely understood in the near future.

PMID- 8886034
TI  - [Present state and future of radiation therapy for pancreatic cancer].
AB  - According to a nation-wide annual report on pancreatic cancer patients in 1992,
      70 percent of patients with pancreatic cancer underwent operations. Thirty
      percent of them, along with 10 percent of patients who did not undergo
      operations, underwent radiation therapy. The result of external radiation
      monotherapy for local advanced pancreatic cancer is so poor that the 2-year
      survival rate and the median survival time have been reported in some papers to
      be approximately 10% and at most 13 months, respectively. Our results indicated
      that the 1-, 2- and 3-year survival rates and the median survival time after
      external radiation monotherapy for local advanced pancreatic cancer were 21%,
      11%, 5% and 11.3 months, respectively. The reasons for the poor results are
      thought to be as follows: pancreatic cancer is very malignant, invades the
      surrounding tissues and metastasizes distantly in its earliest stages; it is
      mostly adenocarcinoma resistant to radiation therapy; and the pancreas borders
      closely the stomach and duodenum, which are very sensitive to radiation.
      Therefore, charged particle radiotherapy, especially heavy ion radiotherapy, is
      expected to bring about advances in the field of radiation therapy for pancreatic
      cancer because of its excellent potential for dose distribution and biological
      effect.

PMID- 8886035
TI  - [Chemotherapy for pancreatic cancer].
AB  - Few antitumor agents are effective for advanced pancreatic cancer. 5
      fluorouracil, doxorubicin, epirubicin, and mitomycin C were tested as single
      agents for their respective efficacy against pancreatic cancer. Their response
      rates were 15, 12, 24 and 24%, respectively. Several trials of combination
      chemotherapy using mitomycin C, doxorubicin and 5-FU (FAM) were performed, but
      their response rates did not go exceed those of single agents. Recently, the goal
      of chemotherapy for pancreatic cancer is thought to be quality of life.
      Combination of 5-FU and cisplatin or 5-FU, leucovorin and alpha interferon were
      effective for the prolongation of life with less toxicities. Their median
      survival times were 7.6 months, and 22 months in PR cases, respectively. CPT-11,
      gemcitabine, taxotere and BOF-A2 are promising new drugs for their effectiveness
      and benefits for patients with pancreatic cancer. Combination of mitomycin C,
      carboquone and 5-FU with angiotensin II was effective in terms of antitumor
      effect and prolongation of life. Generally, a large number of patients with
      advanced pancreatic cancer cannot receive chemotherapy because of deterioration
      in performance status. For them, combination of continuous venous infusion of low
      dose 5-FU and low-dose cisplatin could be effective. The majority of patients
      with pancreatic cancer must await new agents and methodology in the future.

PMID- 8886037
TI  - [New therapeutic approach to pancreatic cancer by monoclonal antibodies].
AB  - The prognosis of pancreatic cancer is extremely poor in digestive cancers even
      with systemic therapy including surgery. Thus development of a new therapeutic
      approach is awaited. Recently, new trials of cancer treatments using monoclonal
      antibodies conjugated with anti-cancer drugs or labeled with isotopes have been
      reported. Here, we discuss the possible therapeutic application for pancreatic
      cancer of adriamycin-conjugated and 131I-labeled Nd2, which is produced against
      pancreatic cancer mucin.

PMID- 8886036
TI  - [Selective thermocoagulation of unresectable malignant tumors using
      radiofrequency].
AB  - Based on our experimental findings on porcine liver, we have been conducting a
      clinical trial of selective hyperthermia by radiofrequency (RF) capacitive
      heating with laparotomy for patients with unresectable malignant tumors. In 10
      patients with malignant tumors (8 carcinoma of the pancreas, 2 carcinoma of the
      gallbladder), laparotomy and RF heating were performed after informed consent.
      The local heat coagulation was produced by heating equipment using 13.56 MHz
      radiofrequency produced by Omron Corporation, Japan. Four 2-cm electrode needles
      were placed in the tumor in a square array at intervals of 2.0 cm. Hyperthermia
      was given for 30 min with a controlled temperature of 50 degrees C in the RF
      field (2 x 2 x 2 cm3). That of the surrounding area was maintained at less than
      40 degrees C. The calculated volume treated by RF ranged between (2 x 2 x 2 cm3)
      x 1 and (2 x 2 x 2 cm3) x 6. We followed all patients by computed tomographic
      (CT) scan 2 weeks after coagulation. Tumor markers in the blood were assayed
      before and 14 days after heating. Follow-up CT scans demonstrated that after the
      tumor mass had been heterogeneously enhanced, it changed to a homogeneous low
      density area in 6 of 10 patients. The levels of tumor markers decreased to lower
      than the pre-treatment values in 9 of 10 patients. In all patients, the changes
      in CT scans and/or decrease in the markers were confirmed. Complications such as
      bleeding or abscess formation were not observed. It was suggested that the
      selective hyperthermia was safely produced by this equipment. The encouraging
      results in these patients justify further clinical trials.

PMID- 8886038
TI  - [Growth inhibition of human pancreatic cancer by farnesyl transferase inhibitor].
AB  - Ras is one of the key components in the signal transduction for cell growth. For
      acquisition of biological activity, Ras protein is required to bind to the inside
      of the plasma membrane after post-translational farnesylation. Manumycin, a
      competitive farnesyl transferase inhibitor, inhibits the growth of human
      pancreatic cancer cells (SUIT-2, MIAPaCa-2, AsPC-1, BxPC-3) in a dose dependent
      manner. The inhibitory concentration (IC50) of cell lines with a mutant K-ras
      gene (SUIT-2, MIAPaCa-2, AsPC-1) was lower than that of BxPC-3 with a wild-type.
      A high concentration of manumycin induced apoptosis, which is related to the
      inhibition of cell growth. Inhibition of Ras activity might be a new anti-cancer
      therapy in pancreatic cancer in which Ras plays a role.

PMID- 8886039
TI  - [A new strategy for the therapy of pancreatic cancer by proton pump inhibitor].
AB  - Bafilomycin A1 is a specific inhibitor of vacuolar type proton pump (V-ATPase).
      This study was designed to examine the effect of bafilomycin A1 on the growth of
      Capan-1 human pancreatic cells which overexpress V-ATPase. Nude mice bearing a
      xenografted tumor of Capan-1 cell line were treated for 4 weeks with bafilomycin
      A1 (1.0 mg/kg/day). This treatment inhibited tumor growth, which was
      significantly reduced as compared with controls after 21 days (p < 0.05).
      However, there were no significant differences in body weights between groups.
      Microscopically, a large number of tumor cells in the treated group showed signs
      of apoptosis. These findings suggest that apoptosis induced by bafilomycin A1 was
      the event involved in suppression of tumor growth in vivo.

PMID- 8886040
TI  - [Application for therapeutic use of deuterium oxide (D2O) against human
      pancreatic cancer].
AB  - This study was designed to assess the possibility of D2O as a therapeutic agent
      against human pancreatic cancer. We examined the effect of D2O on growth and
      invasion of human pancreatic cancer cells (Panc-1, MIA PaCa-2, BxPC-3) by using
      MTT assay and nude mice, on which human pancreas cancer cells were transplanted.
      In vitro growth of the three lines was significantly inhibited by D2O in a dose
      dependent manner, especially at more than a 10% concentration. Growth of Panc-1,
      which was transplanted in nude mice, was also inhibited by continuous oral intake
      of 30% D2O. Furthermore, the effect of D2O on cancer invasiveness was assessed by
      Matrigel invasion chamber assay. BxPC-3, which is the most adherent of the three
      lines, significantly reduced its invasiveness in more than 30% D2O media. In
      addition, the present study also demonstrated the inhibition of cancer cell
      locomotion by D2O in phagocytokinetic analysis. In conclusion, D2O may be applied
      for the therapeutic use against pancreatic cancer.

PMID- 8886041
TI  - [Inhibitory effect of FOY-305 on liver metastasis of the pancreatic cancer].
AB  - The potential for hepatic metastasis in nude mice was studied by the intrasplenic
      implantation method with five human pancreatic cancer cell lines, Capan-1, BxPC
      3, AsPC-1, Panc-1, and MIAPaCa-2, especially in relation to serine protease
      expression, including urokinase-type plasminogen activator and pancreatic
      trypsinogen 1 (cationic form). The inhibitory effect of a serine protease
      inhibitor agent, FOY-305, on hepatic metastasis was also a assessed. As a result,
      the potential for hepatic metastasis was well correlated with expression of
      pancreatic trypsinogen 1 in these cell lines, and the incidence of metastasis was
      significantly decreased by FOY-305. These findings suggest that pharmacologic
      inhibition of serine protease activity may be a new strategy for the therapy of
      pancreatic cancer metastasis.

PMID- 8886042
TI  - [Effect of etoposide on a human pancreatic cancer cell line exposed to high dose
      X-ray irradiation].
AB  - Effects of etoposide on the cell deaths of a human pancreatic cancer cell line by
      exposure to high-dose X-ray irradiation were examined. Both high dose X-ray
      irradiation and etoposide killed the pancreatic cancer cells by apoptosis. With
      30 gray irradiation, simultaneous treatment of etoposide did not alter the
      percentage of cell deaths; however, 24-hr prior treatment of etoposide killed a
      significantly larger percentage of the cells, accompanying the accumulation to
      the S phase of the cell cycle. The results indicate that apoptosis of human
      pancreatic cancer cell line induced by high dose X-ray irradiation can be
      enhanced by prior treatment with etoposide.

PMID- 8886043
TI  - [Probability of vaccine therapy for pancreas cancer].
AB  - To explore the possibility of vaccine therapy for pancreatic cancer using ras
      oncogenic protein related antigen we studied whether cytotoxic T lymphocyte for
      tumor rejection can be induced by vaccination using the peptide relating mutated
      ras protein. Splenocytes from mice immunized by peptide (9-15 mer) relating
      mutated ras protein with normal splenocytes specifically increased in the culture
      with the peptide. The harvested splenic lymphocytes from the mice had peptide
      specific lysis against B 6 fibroblast incubated with the peptide. These results
      suggested that immunization using the peptide relating mutated ras peptide with
      autologous antigen presenting cell can be a vaccine therapy for pancreatic
      cancer.

PMID- 8886044
TI  - [Adoptive immunotherapy for pancreatic cancer, using MUC1 specific CTL].
AB  - A new therapeutic strategy for pancreatic cancer is needed because of its very
      poor prognosis. We presented the results of adoptive immunotherapy and new
      adoptive immunotherapy using MUC1 specific CTL. We expect that these new
      strategies may help improve the prognosis of pancreatic cancer.

PMID- 8886045
TI  - [A late phase II study of LY188011 (Gemcitabine hydrochloride) in patients with
      non-small-cell lung cancer. Gemcitabine Cooperative Study Group B for Late Phase
      II].
AB  - A late phase II study of LY188011 (gemcitabine hydrochloride), a new nucleoside
      derivative, in patients with non-small-cell lung cancer (NSCLC) was conducted at
      24 Japanese institutions shown in Table 1 with a total of 69 patients enrolled.
      Of these, 67 were eligible and 64 completed at least one course of LY188011
      therapy. The response rates (partial response only) in these populations were
      20.9% (14/ 67) and 21.9% (14/64), respectively. Serious adverse reactions were
      septic shock and interstitial pneumonia in one patient each. Grade 3 or 4 adverse
      reactions included neutropenia (22.7%), decreased hemoglobin (13.4%), leukopenia
      (10.4%), anorexia (10.4%), malaise (7.5%), and nausea/vomiting (6.0%). Based on
      these results, it may be concluded that LY188011 has a high efficacy and benefit
      for the treatment of NSCLC.

PMID- 8886046
TI  - [Combination therapy with 5-fluorouracil (5-FU), cisplatin (CDDP) and interferon
      alpha-2B (IFN alpha-2B) for advanced renal cell carcinoma].
AB  - Eleven patients with metastatic renal cell carcinoma received combination therapy
      with 5-fluorouracil (5-FU), Cisplatin (CDDP) and Interferon alpha-2b (IFN alpha
      2b). For 5 days, 500 mg of 5-FU was administered by continuous intravenous
      infusion daily; 20 mg/m2 CDDP was injected intravenously daily for 5 days, and 3
      or 6 million units of IFN alpha-2b was administered intramuscularly twice a week
      for 3 weeks. This treatment cycle was repeated every 3 weeks. One of 11 patients
      achieved a partial response, and the response rate was 9%. High grade toxicities
      (WHO grade 3 or 4), nausea and vomiting (27%), leukocytopenia (9%), anemia (9%)
      and thrombocytopenia (18%) were seen. One of the reasons that this regimen dose
      not appear to be effective may be the low total dose of 5-FU for renal cell
      carcinoma.

PMID- 8886047
TI  - [Clinical usefulness of serum CYFRA21-1 in colorectal cancer].
AB  - Serum CYFRA21-1 levels were studied in 127 cases of colorectal cancer. The
      positive rates for serum CYFRA21-1 were 34.6% in primary colorectal cancer. There
      was a significant correlation between the positive rates of serum CYFRA21-1 and
      liver metastases, peritoneal dissemination, lymph node metastases, or clinical
      stage. The survival rate for patients in the CYFRA21-1 positive group was lower
      than those with CYFRA21-1 negative group. Among patients who underwent curative
      operation, patients is the CYFRA21-1 positive group gave a recurrence rate of
      26.6%, against 9.4% in the CYFRA21-1 negative group. There was no correlation
      between serum CYFRA21-1 levels and serum CEA levels. These findings suggest that
      Serum CYFRA21-1 levels may be a useful indicator in estimating the prognosis for
      colorectal cancer.

PMID- 8886048
TI  - [Clinical effect of intra-arterial carboplatin-combined chemotherapy for advanced
      uterine cervical cancer and increased tissue platinum levels with Lipo PGE1
      administration before chemotherapy].
AB  - Combination chemotherapy including carboplatin was administered intraarterially
      from the internal iliac artery as neoadjuvant chemotherapy to nine patients with
      advanced uterine cervical cancer. Two or three courses were repeated at intervals
      of 3 weeks. And to investigate whether the administration of Lipo PGE1 with the
      action of vasodilation before intra-arterial chemotherapy increases tissue levels
      of anticancer agents, 7 out of 9 patients were treated with Lipo PGE1, followed
      by arterial infusion chemotherapy. After infusion, tissue platinum (Pt)
      concentrations were measured by flameless atomic absorption spectrophotometry.
      Three of 9 patients with measurable tumor had a complete response and 6 had a
      partial response. Tissue Pt concentrations reached maximum levels 2-6 hours after
      intra-arterial chemotherapy. Tissue Pt levels of the patients with pretreatment
      of Lipo PGE1 were significantly higher than those without pretreatment (p <
      0.01). It seems likely that Lipo PGE1 administration before intra-arterial
      chemotherapy is useful for the enhancement of tissue levels of anticancer agents
      as well as the clinical effects.

PMID- 8886049
TI  - [Effective transcatheter arterial embolization for hepatic metastasis in a case
      of AFP producing gastric cancer].
AB  - We experienced a case of effective transcatheter arterial embolization (TAE) for
      hepatic metastasis in a AFP producing gastric cancer. A 51-year-old man with 2
      type gastric cancer (H0) underwent subtotal gastrectomy (D2). The serum AFP level
      was 134.3 ng/ml, and AFP positive tumor cells were detected by PAP method. After
      the operation, the serum AFP level initially decreased but re-increased on the
      7th postoperative month, and metastatic lesions of the liver were detected by CT
      scan. After the patient was treated 4 times by TAE, the serum AFP level returned
      within normal range and the metastatic tumors of the liver decreased markedly.
      Therefore liver resection was performed at the 28th month after the first
      operation. Total necrosis of metastatic liver lesions was confirmed. This patient
      has been well without recurrence signs for 10 years since operation. It is
      concluded that TAE should be used to treat hepatic metastasis in the case of an
      AFP producing gastric cancer.

PMID- 8886050
TI  - [A case of advanced gastric cancer with multiple liver metastasis successfully
      treated with combination chemotherapy using UFT, CDDP and etoposide].
AB  - We reported a 66-year-old male patient with advanced gastric cancer accompanied
      by multiple liver metastasis, who responded to combination chemotherapy using
      UFT, CDDP and etoposide. The patient was administered three courses of 600
      mg/body UFT po daily, 50 mg/body CDDP iv and 50 mg/body etoposide iv on days 1
      and 8 every 4 weeks. As a result, both the primary and metastatic tumors
      decreased remarkably in size. Adverse reactions were leukocytopenia (Grade 2),
      thrombocytopenia (Grade 1) and nausea (Grade 1). he is alive 16 months after the
      beginning of therapy in a condition of partial response (PR). This combination
      therapy seemed to be effective for advanced gastric cancer.

PMID- 8886051
TI  - [Bowel injury caused by a catheter for Intraperitoneal chemotherapy--a case
      report].
AB  - A case of bowel perforation caused by a catheter used for intraperitoneal
      chemotherapy is reported. A 46-year-old woman underwent bilateral salpingo
      oophorectomy, total hysterectomy and infracolic omentectomy for treatment of
      stage II c endometrioid carcinoma of ovary. Subsequently, the patient was treated
      with intraperitoneal administration of CBDCA through Port-A-Cath as well as
      intravenous CPA infusion every 5-6 weeks. Ten days after the 5th course of
      chemotherapy, she complained of low abdominal pain and fever of 37.9 degrees C,
      which resolved during a 6-day hospital stay, although her appetite remained poor.
      In the 6th course, CBDCA was administrated intravenously, because the
      intraperitoneal catheter became obstructed. Secondary cytoreductive laparotomy,
      which was performed 14 months after the primary surgery, revealed that the
      catheter of Port-A-Cath had penetrated the descending colon. Although
      intraabdominal injury by the catheter may be rare, it should be noted as one of
      complications when a patient is treated with intraperitoneal chemotherapy.

PMID- 8886052
TI  - [Treatment of refractory hematologic malignancies by combination of cytarabine
      ocfosfate and etoposide].
AB  - We attempted a combination chemotherapy with cytarabine ocfosfate (SPAC) and
      etoposide for myelodysplastic syndrome (MDS), and acute non-lymphocytic leukemia
      developing after a prior history of MDS (MDS/ANLL). SPAC and etoposide were
      administered orally at the dose of 200 mg/day and 25 mg/day for 14 days, as
      standard regimen. Two cases complete remission (CR), 4 of partial remission (PR)
      were obtained among 9 patients. The plasma concentration of cytarabine (Ara-C)
      reached a plateau at around 4.5 ng/ml during the treatment period from the 7th to
      the 14th day, and it was detectable with a gradual decrease until the 28th day in
      spite of the last administration of SPAC on the 14th day. It is suggested that
      this combination chemotherapy is useful against MDS, MDS/ANLL and other resistant
      leukemia, especially in elderly patients who can not be treated by intensive
      combination chemotherapy.

PMID- 8886053
TI  - [Concurrent radiotherapy and chemotherapy for non-small-cell lung cancer-
      continuous infusion of low dose cisplatin and 5-FU].

PMID- 8886054
TI  - Recommendations of the first Michigan conference on prostate cancer.

PMID- 8886055
TI  - Neoadjuvant therapy prior to radical prostatectomy: pro.

PMID- 8886056
TI  - Neoadjuvant androgen-deprivation therapy prior to radical prostatectomy: con.

PMID- 8886058
TI  - Alpha-blockade: monotherapy for hypertension and benign prostatic hyperplasia.

PMID- 8886059
TI  - Detection of human papillomavirus DNA in primary squamous cell carcinoma of the
      male urethra.
AB  - OBJECTIVES: The prevalence of human papillomavirus deoxyribonucleic acid (DNA) in
      primary squamous cell carcinoma of the male urethra and corresponding control
      tissue was studied. METHODS: The technique of polymerase chain reaction DNA
      amplification was used to detect specific human papillomavirus DNA sequences in
      archival pathologic and control tissue. We analyzed 16 cases of primary squamous
      cell carcinoma of the male urethra and 22 specimens of normal male urethra
      stratified by location within the urethra. RESULTS: Primary squamous cell
      carcinoma of the pendulous urethra was significantly associated with human
      papillomavirus type 16 DNA (6 of 6 cases), but the control tissue from the
      pendulous urethra was not (0 of 12, P < 0.001). Primary squamous cell carcinoma
      of the bulbous and posterior urethra was not associated with human papillomavirus
      infection. CONCLUSIONS: Infection of the male urethra with human papillomavirus
      type 16 may have a role in the pathogenesis of primary squamous cell carcinoma of
      the pendulous urethra, for which it has a strong predilection, vis-a-vis the
      bulbous and posterior urethra.

PMID- 8886060
TI  - Radiographic prognostic criteria for extracorporeal shock-wave lithotripsy: a
      study of 485 patients.
AB  - OBJECTIVES: We studied 485 patients treated by extracorporeal shock-wave
      lithotripsy (ESWL) using an ultrasound electrohydraulic apparatus in an effort to
      define radiographic criteria for better patient selection for ESWL. METHODS:
      Results were assessed according to plain x-ray nephrotomography and ultrasound.
      The criteria for measuring success (stone free [SF]) excluded all residual
      fragments. After per-criteria analysis of the results, a multivariate analysis as
      well as an analysis of stone composition by infrared spectroscopy were performed.
      RESULTS: The SF rate was 57.5% (279 of 485). Calculi that were smooth, denser
      than bone, located in the lower calyx, and larger than 15 mm had less
      satisfactory results despite a greater number of impulses. A correlation was
      established between the radiographic appearance of the calculus, its composition,
      and ESWL results. Rough, less dense calcium oxalate dihydrate yielded
      satisfactory results (65%), whereas smooth, dense calcium oxalate monohydrate led
      to less conclusive results (41%). Multivariate analysis demonstrated the
      predominant influence of radiographic calculus profile on the results: rough,
      less dense calculi yielded a 79.4% SF rate, whereas smooth, dense calculi yielded
      a 33.6% SF rate. CONCLUSIONS: We propose that patients with dense, smooth calculi
      located in the lower calyx and larger than 15 mm be treated by other techniques,
      such as percutaneous nephrolithotomy. This would not only increase the ESWL
      effectiveness rate, but would also reduce the cost of treating kidney stones.

PMID- 8886061
TI  - Laparoscopic complications in markedly obese urologic patients (a multi
      institutional review)
AB  - OBJECTIVES: Significant obesity is considered to be a relative contraindication
      to laparoscopic surgery. This study reviews the complications encountered in
      massively obese patients undergoing urologic laparoscopic surgery. METHODS: Body
      mass index (BMI) was used as an objective index to indicate massive obesity.
      Eleven institutions compiled retrospective data on 125 patients having a BMI
      greater than 30. Procedures performed included 76 pelvic lymph node dissections,
      14 nephrectomies, 7 bladder neck suspensions, and 28 miscellaneous procedures.
      RESULTS: For the group as a whole, the mean BMI was 35.1 (range 30.1 to 57.2).
      Mean operative time was 202 minutes (range 60 to 480). Conversion to open surgery
      occurred in 15 of the 125 patients (12%). Complication rates (minor and major)
      were 22% (27 occurrences in 125 patients) intraoperatively and 26% (33
      occurrences in 125 patients) postoperatively. The major complications included 2
      trocar injuries to abdominal wall vessels, 1 bladder injury, 3 peripheral nerve
      injuries, 1 dysrhythmia, 1 deep vein thrombosis, 1 wound seroma, 1
      nephrocutaneous fistula, 1 incisional hernia, and 1 death. CONCLUSIONS: In this
      review, complication rates for urologic laparoscopic surgery on massively obese
      patients were higher than in the general population undergoing laparoscopic
      surgery (0.3% to 21%).

PMID- 8886062
TI  - Chronic prostatitis: results of an Internet survey.
AB  - OBJECTIVES: Chronic prostatitis is a common diagnosis, but the etiology of this
      disease is unknown. We sought to catalog symptoms and etiologic factors for
      chronic prostatitis to gather epidemiologic data about the disease. We also
      sought to determine the feasibility of doing this using the Internet. METHODS: A
      54-questions survey was designed and posted to several Internet newsgroups
      dealing with chronic prostatitis. The questions dealt with symptoms, predisposing
      factors, demographic data, and sexual practices. Responses were collected by
      electronic mail and tabulated at a central site. RESULTS: We received 163
      completed surveys over a 2-month period. Nine percent of responses came from
      individuals outside the United States or Canada. Only 9.8% of complete surveys
      contained one or more unreadable answers. The responding population consisted of
      relatively young men (mean age 43 years) with a chronic, relapsing set of
      symptoms mostly characterized by pain at various locations in the pelvis,
      irritative voiding symptoms, and pain associated with ejaculation. Most
      respondents were potent and had a single sexual partner. CONCLUSIONS: This
      catalog of symptoms will be useful in the design of a standardized instrument to
      distinguish the population of men with prostatitis from normal men or men with
      benign prostatic hyperplasia. The facility of conducting patient surveys by
      Internet is demonstrated.

PMID- 8886063
TI  - Potassium-titanyl-phosphate laser vaporization of the prostate: a comparative
      functional and pathologic study in canines.
AB  - OBJECTIVE: We compared the functional and pathologic results of potassium-titanyl
      phosphate (KTP) laser vaporization prostatectomy with those of neodymium:yttrium
      aluminum-garnet (Nd:YAG) laser vaporization and coagulation prostatectomy in
      dogs. METHODS: The prostates of 41 dogs were treated with KTP laser vaporization
      (n = 21), Nd:YAG laser vaporization (n = 10), or Nd:YAG laser coagulation (n =
      10). Dogs were sacrificed 2 days or 8 weeks after treatment. Prostates were
      weighed, measured, serially sectioned, and whole-mounted for histologic analysis.
      RESULTS: All techniques were hemostatic, and no irrigant absorption was detected.
      KTP laser vaporization produced a prostatic defect with a mean diameter of 3.0
      and 2.4 cm at 2 days and 8 weeks postoperatively, respectively. Smaller defects
      (P < 0.0005 at 2 days and P < 0.02 at 8 weeks) were produced by Nd:YAG laser
      vaporization (2.0 and 1.4 cm, respectively) and coagulation (0.5 and 0.9 cm,
      respectively). No dog treated with KTP laser vaporization was incontinent or
      developed urinary retention, including 5 dogs whose urethral catheters were
      removed within 24 hours of surgery. CONCLUSIONS: KTP laser vaporization
      prostatectomy not only provides hemostasis similar to that obtained with Nd:YAG
      laser coagulation, but also removes tissue at the time of operation, allowing
      dogs to void without straining within 24 hours of treatment. In addition, the
      procedure is technically simple, and the operator has excellent control over
      exactly which tissue is removed and which is left intact. These findings suggest
      that KTP laser vaporization may be useful in the treatment of human benign
      prostatic hyperplasia.

PMID- 8886064
TI  - High-energy visual laser ablation of the prostate in men with urinary retention:
      pressure-flow analysis.
AB  - OBJECTIVES: To assess the efficacy of high-energy visual laser ablation of the
      prostate (VLAP) in men with urinary retention, using subjective and objective
      data. METHODS: Seventeen men in urinary retention underwent high-energy VLAP. The
      mean patient age was 69 years, and the mean follow-up was 12 months. All men were
      urodynamically obstructed by pressure-flow analysis with a functioning detrusor
      muscle. Interviews assessed retrograde ejaculation and patient satisfaction.
      RESULTS: The mean total energy applied was 71,088 J (range 27,556 to 110,294).
      The mean peak noninvasive urine flow rates increased from 2.1 to 18.1 cc/s, and
      the mean postvoid residual volumes decreased from 550.0 to 39.0 cc. The mean
      detrusor pressure at peak flow decreased from 66.4 to 41.9 cm H2O, and the mean
      maximal detrusor pressure decreased from 72.2 to 49.2 cm H2O. Ten men (59%)
      voided to completion within 1 week post-VLAP. The mean postoperative
      International Prostate Symptom Score was 6. Nine men (53%) reported new
      retrograde ejaculation, and 14 men (82%) were satisfied with their outcome.
      CONCLUSIONS: High-energy VLAP is an effective procedure for relief of bladder
      outlet obstruction in men with urinary retention.

PMID- 8886065
TI  - Long-term outcome of prostatic stent treatment for benign prostatic hyperplasia.
AB  - OBJECTIVES: To evaluate the long-term result of prostatic stent treatment for
      patients with benign prostatic hyperplasia (BPH). METHODS: We reviewed our
      experience with prostatic stents in 24 patients with bladder outlet obstruction
      caused by BPH for whom up to 63 months of follow-up data were available. RESULTS:
      Prostatic stents were successfully placed in 24 of 25 patients enrolled in the
      study. All 9 patients treated for urinary retention voided spontaneously after
      stent placement. In 14 (93%) of 15 patients with nonretention, voiding symptoms
      decreased by 50% or more. The stent was removed in 9 patients for persistence of
      symptoms, symptom recurrence, or stent migration. Nine patients died of unrelated
      causes during the follow-up period. The stents functioned adequately in these
      patients until death. In the remaining 6 patients, the stent was still in place
      at the last follow-up visit (range 12 to 52 months, average 35) after placement,
      and their Madsen-Iversen symptom scores ranged from 3 to 10. Fourteen patients
      underwent cystoscopy 1 to 37 months after stent placement. Epithelium did not
      completely cover the stent in any of these patients; however, no stone formation
      was noted. CONCLUSIONS: Prostatic stents can be effective in relieving bladder
      outlet obstruction caused by BPH. They appear to be most useful in patients at
      high surgical risk and with a limited life expectancy. However, stent removal,
      which can be difficult, may be required in more than one-third of patients. We
      recommend prostatic stent placement primarily in patients who would otherwise be
      relegated to an indwelling catheter.

PMID- 8886066
TI  - Detection of locally recurrent prostate cancer after cryosurgery: evaluation by
      transrectal ultrasound, magnetic resonance imaging, and three-dimensional proton
      magnetic resonance spectroscopy.
AB  - OBJECTIVES: To assess and compare the clinical usefulness of transrectal
      ultrasound (TRUS), magnetic resonance imaging (MRI), and three-dimensional proton
      magnetic resonance spectroscopic imaging (3-D MRSI) in detecting local recurrence
      of carcinoma of the prostate (CaP) in patients with detectable prostate-specific
      antigen (PSA) levels after cryosurgery. METHODS: In a prospective study, 25
      patients who had undergone cryosurgery as primary treatment for CaP underwent
      endorectal MRI and 3-D MRSI, followed by TRUS-guided prostate biopsy. At the time
      of study, 20 patients had detectable PSA; the remaining 5 patients served as
      controls. All patients had random sextant and guided prostate biopsy for
      correlation with imaging and MR spectroscopic findings. RESULTS: In patients with
      detectable PSA, MRSI identified, location-for-location, all foci of CaP and
      benign prostatic tissue that were detected by prostate biopsy. MRSI identified
      more sites with CaP than did prostate biopsy, indicating a larger volume of
      cancer. In 2 patients with detectable PSA and negative prostate biopsy, MRSI
      identified 11 voxels with viable prostatic tissue. In patients with undetectable
      PSA, both MRSI and prostate biopsy showed necrosis. Ultrasound and MRI were very
      poor tools for identifying recurrent cancer and differentiating between viable
      and necrotic prostate tissue. CONCLUSIONS: 3-D MRSI is superior to TRUS and MRI
      in differentiating among CaP, BPH, and necrosis when local recurrence after
      cryosurgery is suspected. By providing chemical mapping of the prostate in
      contiguous voxels, the addition of spectroscopy to endorectal MRI increases the
      sensitivity for detection of local recurrence.

PMID- 8886067
TI  - Mechanism of healing of the human prostatic urethra following thermal injury.
AB  - OBJECTIVES: To characterize histopathologically the healing response of the
      prostatic urethra after laser thermal coagulation and standard transurethral
      resection of the prostate (TURP). METHODS: The study included 31 patients who
      underwent radical prostatectomy because of malignancy. Twenty-two (first group)
      had laser radiation either at the time of surgery (18 patients) or from 1 to 12
      weeks prior to prostatectomy (4 patients). Nine patients (second group) had TURP
      from 6 to 96 weeks prior to prostatectomy. RESULTS: Coagulation necrosis followed
      by sloughing was observed during the first 10 weeks after laser radiation. After
      the first 10 weeks, the healing response was otherwise stereotypical and
      comparable for both groups of patients. Re-epithelialization was prominent and
      resulted from migration of proliferating epithelial cells from the remaining
      acinar and ductal epithelium. Squamous metaplasia was conspicuous and present
      indefinitely. Development of inflammatory reaction followed by granulation tissue
      and well-organized fibroblastic stroma were sequentially recognized, but less
      prominent. Complete re-epithelialization and wound sealing was not observed
      before the first 12 weeks of healing. CONCLUSIONS: Our study suggests that laser
      thermal coagulation and TURP are partial-thickness injuries. Because of the
      abundant germinal epithelium in the remaining prostatic glands and ducts, the
      healing response of the prostatic urethra is relatively unimpeded and free of
      contractures, analogous to second-degree skin burns.

PMID- 8886068
TI  - Operations for stress urinary incontinence in the United States, 1988-1992.
AB  - OBJECTIVES: To determine the frequency and cost of operations for stress urinary
      incontinence in the United States. METHODS: We reviewed data from the 1988-1992
      National Hospital Discharge Surveys and the 1991 California Office of Statewide
      Health Planning Survey. We determined the frequency and type of surgical
      procedures performed for stress urinary incontinence and estimated the total
      direct costs of these operations in the United States. RESULTS: From 1988 to
      1992, the total number of operations for stress incontinence increased from
      78,000 to over 100,000. The rate of operations increased most in women older than
      65 years of age. The total direct cost for treatment of stress urinary
      incontinence in the United States in 1991 was about $0.5 billion. CONCLUSIONS:
      Operations for treatment of stress urinary incontinence are increasing in
      frequency in the United States. They are both more commonly performed and more
      costly than have been previously reported.

PMID- 8886069
TI  - Cystic renal disease and tuberous sclerosis in infants.
AB  - We describe 2 infants who presented with autosomal dominant-like polycystic
      kidney disease. Evaluation revealed that both children had tuberous sclerosis,
      with resulting cystic kidney disease. This diagnosis should be suspected in
      infants who present with bilateral, large renal cysts, and no family history of
      autosomal dominant polycystic kidney disease.

PMID- 8886070
TI  - Hypospadias repair by laser tissue soldering: intraoperative results and follow
      up in 30 children.
AB  - OBJECTIVES: We examined the use of laser tissue soldering (LTS) as an adjunct to
      suturing of, as well as a primary means of, tissue closure in urethral
      reconstruction. METHODS: Since June 1994, 26 boys ranging in age from 3 months to
      14 years (mean 3.0 years) underwent hypospadias repair using LTS techniques. The
      classification of hypospadias was subcoronal in 13, midpenile in 5, penoscrotal
      in 7, and scrotal in 1. Laser tissue soldering was used in an additional 4
      patients: tunica vaginalis patch graft corporoplasty in 2 (scrotal hypospadias),
      epispadias fistulae in 1, and urethral diverticulum in 1. Of these cases, 3
      hypospadias repairs were completely sutureless. An intraoperative comparision was
      made between suturing and LTS with respect to operative time and degree of
      difficulty in performing LTS. Postoperatively, patients were examined to
      determine complications, including stricture, fistula, or impaired wound healing.
      An unselected group of 25 consecutive boys undergoing hypospadias repair between
      1991 and 1992 served as a historical control group. RESULTS: No intraoperative
      complications resulted from laser activation. In 5 of the 30 procedures (16.6%),
      suture disruption was noted to occur, with a higher incidence seen with finer,
      dyed suture material. For hypospadias repair, the average time to suture was 6.7
      min/cm (n = 23), whereas it was 3.1 min/cm for adjunctive LTS (n = 23) and 1.4
      min/cm for sutureless urethroplasty (n = 3). Follow-up ranged from 3 to 22 months
      (average 9.6). Four fistulae were noted (1 onlay, 2 skin tube grafts, 1 Thiersch
      tube) each following penoscrotal or scrotal hypospadias repair; a fifth fistula
      developed following a traumatic catheterization in a sutureless repair. The
      overall complication rate in the LTS group was 19% (5 of 26) versus 24% (6 of 25)
      for controls, whereas that for the distal forms of hypospadias was 11% (2 of 18)
      and 13.6% (3 of 22), respectively. CONCLUSIONS: Tissue soldering with laser and
      chromophore-doped solder is feasible, safe, and easy to perform. Laser tissue
      soldering may be an alternative to standard microsuture technique for hypospadias
      repair.

PMID- 8886071
TI  - Radiation risk to the urologist during endourologic procedures, and a new shield
      that reduces exposure.
AB  - OBJECTIVES: With the increasing use of endourologic procedures to diagnose and
      treat urologic problems, the urologist's exposure to radiation from fluoroscopy
      becomes an important safety consideration. Although collimation of the x-ray beam
      generally prevents direct radiation exposure by the urologist, the patient
      absorbs radiation during the procedure and becomes a secondary source of exposure
      through radiation scatter. METHODS: We measured radiation exposure to the
      urologist during endourologic procedures using standard body shields and thyroid
      collars. We repeated our surveys using a newly designed urologic surgery
      radiation shield. RESULTS: We found dose rates to the urologist of up to 1100
      mrem per hour of flouroscopy time. The maximum yearly whole-body exposure as
      recommended by the National Council on Radiation Protection is 5000 mrem, or 5
      rem. CONCLUSIONS: Urologists should be cognizant of this radiation risk, and the
      concepts of time, distance, and shielding are critically important to know in
      efforts to reduce radiation exposure. We introduce a newly designed fluoroscopic
      drape which reduces the radiation dosage to the urologist from scatter nearly 70
      fold. We found this shield to be very practical and easy to use, and we offer it
      as an effective safeguard against secondary radiation exposure.

PMID- 8886072
TI  - Use of a subcutaneous tunnel following replantation of an amputated penis.
AB  - We describe a new technique for immobilization and protection of the penis
      following microsurgical replantation, using a subcutaneous tunnel created in the
      suprapubic area. This tunnel protects the phallus from reinjury while maintaining
      an anatomic position and a normothermic environment in the immediate
      postoperative period.

PMID- 8886073
TI  - Bladder cancer.

PMID- 8886074
TI  - Primary thyroidlike carcinoma of the kidney.
AB  - We present a unique papillary thyroidlike carcinoma of the kidney. The patient
      had an incidentally discovered renal mass that, histologically and
      immunohistochemically, resembled papillary thyroid carcinoma. Workup revealed no
      primary site other than the kidney and no evidence of metastasis. This is the
      first reported case of a malignant papillary thyroidlike cancer of the kidney.

PMID- 8886075
TI  - Local recurrence of renal cell carcinoma causing duodenal-inferior vena caval
      fistula: case report and review of the literature.
AB  - We report the first case of a duodenal-inferior vena caval (IVC) fistula
      resulting from locally recurrent renal cell carcinoma (RCC). A 45-year-old man
      presented with gross hematuria and underwent a right radical nephrectomy to treat
      a solid renal mass. Histologic evaluation showed RCC, Stage pT3aN0M0. The patient
      presented 21 months later in hemorrhagic shock, with upper gastrointestinal
      bleeding. He underwent an exploratory laparotomy and Whipple procedure for a mass
      in the second portion of the duodenum extending to the inferior vena cava with a
      secondary duodenal-IVC fistula. We describe this case and review the previously
      published reports of duodenal-IVC fistulae.

PMID- 8886076
TI  - Ultrasound diagnosis of filarial funiculoepididymitis.
AB  - Genital presentation of filarial disease is not uncommon in endemic areas of the
      world. Acute, febrile illness involving the epididymis and spermatic cord
      (funiculoepididymitis) is one of many such presentations. With an internationally
      mobile society, physicians today, even in nonendemic areas, may encounter
      patients with filarial infestations. We report the first case of presumptive
      diagnosis of this disease using scrotal ultrasound.

PMID- 8886077
TI  - Leydig cell hyperplasia mimicking testicular neoplasm.
AB  - Patients with extragonadal seminoma are at high risk of developing a primary
      testicular neoplasm many years after the initial diagnosis and therapy.
      Therefore, long-term follow-up is critical in the proper management of these
      patients. We present the first case of Leydig cell hyperplasia, mimicking a
      testicular neoplasm, 21 years after diagnosis and treatment of extragonadal
      seminoma.

PMID- 8886078
TI  - Histopathologic characterization of hereditary benign prostatic hyperplasia.
AB  - OBJECTIVES: Recent studies suggest the presence of a hereditary form of benign
      prostatic hyperplasia (H-BPH). This study was undertaken to characterize the
      histopathologic features of BPH in these men. METHODS: Because study subjects
      with H-BPH were young (mean age 59 years) and had a large prostate (mean prostate
      weight 61 g), we compared the histopathologic findings in these men with those in
      two different control groups: (1) age-matched control subjects (mean age 59
      years; mean prostate weight 31 g), and (2) prostate weight-matched control
      subjects (mean age 70 years; mean prostate weight 61 g). Using a color video
      image analysis system, we morphometrically determined stromal/epithelial ratios
      in histologic sections taken from 12 men with H-BPH, 36 age-matched control
      subjects, and 36 prostate weight-matched control subjects. RESULTS: The
      stromal/epithelial ratio was 2.6 +/- 1.4 in the men with H-BPH, 2.7 +/- 1.7 in
      the age-matched control subjects, and 1.7 +/- 0.9 in the prostate weight-matched
      control subjects. Regression analysis, which controlled for the differences in
      prostate weight or patient age between men with H-BPH and age-matched and
      prostate weight-matched control subjects, respectively, revealed a significant
      difference between men with H-BPH and prostate weight-matched control subjects (P
      = 0.015) but no difference from age-matched control subjects (P = 0.36).
      CONCLUSIONS: The larger prostates in young men with H-BPH are characterized by a
      higher stromal/epithelial ratio than are similar-sized prostates in older men
      with sporadic BPH. This finding gives rise to speculation that H-BPH is
      associated with an increase in stromal elements.

PMID- 8886079
TI  - Testosterone and prolactin stimulation of mitochondrial aconitase in pig prostate
      epithelial cells.
AB  - OBJECTIVES: The function of the prostate gland in many animals, including humans,
      is to accumulate and secrete large quantities of citrate. This function derives
      from the metabolic characteristics of the prostate secretory epithelial cells.
      These cells possess a uniquely limiting mitochondrial aconitase (m-aconitase)
      that minimizes citrate oxidation and thus permits citrate to accumulate.
      Unfortunately, the characteristics of prostate m-aconitase and its manner of
      regulation have not been established. The hormones testosterone and prolactin,
      however, are significantly involved in regulating prostate citrate production.
      Thus it is reasonable to hypothesize that these hormones may be involved in the
      regulation of both m-aconitase and citrate oxidation. METHODS: Using freshly
      prepared pig prostate epithelial cells, we attempted to determine the effects of
      testosterone and prolactin treatment on the level of m-aconitase enzyme, on the
      level of m-aconitase activity, and on citrate utilization. The epithelial cells
      were incubated for 3 hours with either testosterone (10(-9) M), prolactin (1
      microgram/mL), or vehicle (control). RESULTS: Both hormone applications caused a
      marked increase in the level of m-aconitase. In contrast, neither hormone had any
      effect on the m-aconitase level of pig seminal vesicle cells, which are also
      citrate-producing cells. Moreover, neither hormone had any effect on pyruvate
      dehydrogenase E1a. These findings suggest that testosterone and prolactin
      regulation of prostate m-aconitase is a highly specific effect. Along with the
      increase in the level of m-aconitase enzyme, both hormones also increased m
      aconitase activity and prostate-cell utilization of citrate. CONCLUSIONS: These
      studies demonstrate that testosterone and prolactin can regulate m-aconitase and
      sub-sequent citrate oxidation of specific prostate epithelial cells. This unique
      aconitase relationship is not observed in other mammalian cells.

PMID- 8886080
TI  - Mucinous adenocarcinoma of the prostate: a report of a case of long-term
      survival.

PMID- 8886081
TI  - Same day surgery for radical retropubic prostatectomy: is it an attainable goal?

PMID- 8886082
TI  - A controlled trial of bicalutamide versus flutamide, each in combination with
      luteinizing hormone-releasing hormone analogue therapy, in patients with advanced
      prostate cancer.

PMID- 8886083
TI  - A new approach to the treatment of osteoarthritis: viscosupplementation.

PMID- 8886084
TI  - Moderate exercise exacerbates the osteoarthritic lesions produced in cartilage by
      meniscectomy: a morphological study.
AB  - Unilateral medial meniscectomy was performed on two groups of sheep. At 1 week
      post-operatively, one group (N = 5) underwent a regimen of moderate walking
      exercise (24 km/week), while the other group (N = 5) received no exercise. Two
      groups (N = 6 and 8) of unoperated sheep were used as exercised and unexercised
      controls for the respective meniscectomized groups. Six months post-surgery all
      groups were sacrificed and their knee joints were examined macroscopically using
      established scoring systems. In both groups, meniscectomy induced cartilage and
      bone changes typical of early hypertrophic osteoarthritis. However,
      meniscectomized animals subjected to the exercise program developed more severe
      cartilage lesions and osteophytes than their unexercised counterparts. While the
      cell density in femoral cartilage of the meniscectomized and exercised group was
      similar to controls, that of the meniscectomized but unexercised animals was
      higher. We conclude form these data that in this animal model exercise
      exacerbated the lesions induced in articular cartilage by meniscectomy.

PMID- 8886085
TI  - High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the
      knee: a 1 year placebo-controlled trial.
AB  - Hyaluronic acid is a natural component of cartilage and is considered not only as
      a lubricant in joints but also as playing a physiological role in the trophic
      status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted
      from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To
      assess the efficacy and tolerability of intra-articular injections of hyalectin,
      we conducted a prospective, randomized, placebo-controlled trial of 1 years'
      duration in 110 patients with painful hydarthrodial osteoarthritis of the knee.
      At entry and once a week for 3 weeks, aspiration of the knee effusion and intra
      articular injections of either hyalectin 20 mg (H) or its vehicle (C) were
      performed. The vehicle acted as the control treatment. Four weeks after the last
      injection, the improvement was greater in the H group compared with the C group
      (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional
      index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the
      need to perform supplementary local therapies (joint fluid aspiration because of
      painful hydarthrodial episodes and/or local corticosteroid injections) was more
      frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the
      physician's overall assessment of efficacy was in favor of H (77% vs 54%, P =
      0.01) and the improvement in the functional index was greater in group H (-4.4 +/
      5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular
      injections of hyalectin may (1) improve clinical condition and (2) have a long
      term beneficial effect in patients with osteoarthritis of the knee.

PMID- 8886086
TI  - Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and
      sodium pentosan polysulfate.
AB  - The potential therapeutic effects of insulin-like growth factor-1 (IGF-1) and
      sodium pentosan polysulfate (PPS) were evaluated in an anterior cruciate ligament
      deficient canine model of osteoarthritis (OA). A control group of animals
      received no treatment or surgery (N). The remaining four groups of animals
      received anterior cruciate transection and either no treatment (OA), intra
      articular IGF-1 (IGF-1), intra-muscular PPS (PPS), or a combination of intra
      articular IGF-1 and intra-muscular PPS (IGF-1/PPS). All therapy was begun 3 weeks
      after surgery and continued for 3 weeks. At 6 weeks, articular cartilage from the
      femoral condyle was evaluated for anatomy, histology (Mankin grade) and
      biochemistry. Anatomically, only cartilage from dogs in the IGF-1/PPS group
      approximated that found in N. Mankin scores indicated less severe disease in both
      PPS and IGF-1/PPS groups compared with the OA group. Consistent with histology,
      the level of active neutral metalloproteinase was lower in cartilage from the PPS
      group compared with the OA group. Active and total neutral metalloproteinase,
      tissue inhibitor of metalloproteinases (TIMP), total collagenase, uronate and
      hydroxyproline contents were all near normal in the IGF-1/PPS group. In a model
      of mild OA, therapeutic intervention with IGF-1 and PPS appeared to successfully
      maintain cartilage structure and biochemistry. From these data, it is
      hypothesized that proteinase activity was successfully blocked by PPS, and that
      this allowed the observed growth factor induced effects. As we unravel the
      various factors that regulate cartilage metabolism, it is becoming apparent that
      combinations of agents will be needed to effectively control cartilage repair in
      OA. The addition of PPS to IGF-1 shows promise as a therapeutic intervention and
      introduces a new rational approach to therapy of OA.

PMID- 8886087
TI  - Metalloprotease activity, phospholipase A2 activity and cytokine concentration in
      osteoarthritis synovial fluids.
AB  - Collagenase, stromelysin and phospholipase A2 (PLA2) activity as well as
      interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and
      interleukin 6 (IL-6) concentration were determined in the knee joint synovial
      fluid (SF) of 26 patients with osteoarthritis (OA) and with rheumatoid arthritis
      (RA). Collagenase and stromelysin were detected in 80.7 and 69.2% of OA SF,
      respectively. When present, the mean activity of both enzymes was approximately
      two times lower in OA than in RA SF. PLA2 activity was present in all SF with no
      significant difference between OA and RA SF. IL-1 beta, TNF alpha and IL-6 were
      found in 0, 96.1 and 84.6% of OA SF, respectively. Mean TNF alpha and IL-6
      concentration was also lower in OA than in RA SF. Metalloprotease activity
      correlated weakly with IL-6 level and enzymatic activities were unrelated with
      TNF alpha in OA SF.

PMID- 8886088
TI  - Joint fluid carboxy-terminal type II procollagen peptide as a marker of cartilage
      collagen biosynthesis.
AB  - Joint fluid levels of carboxy-terminal type II procollagen peptide (pCOL II-C)
      were measured in osteoarthritis, rheumatoid arthritis and traumatic arthritis by
      a newly developed one-step enzyme immunoassay (EIA). The detection limit of the
      new method was as low as 0.2 ng/ml. The levels of pCOL II-C were significantly (P
      < 0.001) higher in osteoarthritis and traumatic arthritis than in rheumatoid
      arthritis. In osteoarthritis, pCOL II-C levels were higher in moderately
      afflicted patients. Since type II collagen is a unique component of cartilage,
      pCOL II-C levels in joint fluids could reflect the synthetic activity of type II
      collagen of chondrocytes in the diseased joint and therefore could be utilized as
      a simple marker of type II collagen synthesis in articular cartilage in joint
      diseases.

PMID- 8886089
TI  - Obesity and osteoarthritis of the hands in women.
AB  - The association of obesity and body fat distribution with hand osteoarthritis was
      studied in 317 Caucasian female subjects aged 40 years and above in the Baltimore
      Longitudinal Study of Aging. Bilateral hand radiographs taken between 1978 and
      1991 were read by one investigator for grade of osteoarthritis using Kellgren
      Lawrence scales. Possible risk factors, assessed at same visit as the first
      radiograph during this interval, included age and measures of obesity, per cent
      body fat, and fat distribution. Results of bivariate analyses showed that
      increasing grade of hand osteoarthritis was associated with increasing age,
      greater mean levels of waist-hip ratio and per cent body fat; there was no
      association with body mass index. After adjustment for age, however, none of
      these independent variables remained significantly associated with grade of hand
      osteoarthritis. These data fail to support hypotheses that measures of obesity
      are associated with hand osteoarthritis in women independent of their known age
      related changes.

PMID- 8886090
TI  - The control of cell division in articular chondrocytes.
AB  - Our objective was to investigate the factors that control chondrocyte division,
      namely, (1) steric hindrance caused by the surrounding matrix, (2) growth factors
      and (3) cell shape. Bovine articular cartilage explants and isolated chondrocytes
      were cultured in medium containing [3H]-TdR to measure DNA synthesis. The effect
      of enzyme treatment, growth factors and cell shape was investigated. Proteoglycan
      (PG) depletion did not stimulate DNA synthesis whilst disruption of the collagen
      architecture promoted incorporation of [3H]-TdR into DNA. DNA synthesis was also
      stimulated by IGF-1 in flattened chondrocytes but not in rounded cells. It was
      found that the control of chondrocyte division depends on several variably
      related factors that may act singly or together to induce cell division and that
      PG depletion alone is insufficient to induce DNA synthesis, but division was
      noted when PG depletion was accompanied by matrix disruption and cell shape
      changes. Cell shape appears to alter the chondrocytes ability to respond to IGF-1
      as a mitogen.

PMID- 8886091
TI  - Detection of sugarcane bacilliform virus in sugarcane germplasm.
AB  - Sugarcane bacilliform virus (SCBV), a badnavirus was found in sugarcane genotypes
      of Saccharum officinarum L., S. barberi Jesw., S. sinense Roxb., S. robustum
      Brand and Jesw., and Saccharum hybrids. In most of the suspected genotypes the
      virus was found associated with clear foliar symptoms. However, certain symptom
      free clones carried the virus too. The virus was detected by immuno-electron
      microscopy (IEM) and enzyme-linked immunosorbent assay (ELISA) in suspected
      clones. The virions measured about 108-118 x 20-21 nm in size. The virus was
      serologically closely related to another badnavirus, banana streak virus (BSV).
      Virus titer was low in most of the genotypes. However, a close correlation
      between symptoms expression and virus titer existed in some genotypes.

PMID- 8886092
TI  - Stability of foot-and-mouth disease virus, its genome and proteins at 37 degrees
      C.
AB  - Infectivity titers of foot-and-mouth disease virus (FMDV) types Asia 1 and 0 were
      reduced by 4 and 2 log units, respectively, after incubation at 37 degrees C for
      12 hrs. The stability of the FMDV RNA genome at 37 degrees C was studied using
      32P-labelled virus. The RNA of FMDV type 0 was found to be more stable than that
      of type Asia 1. Oligo(dT)-cellulose chromatography showed that 21% and 31% of the
      labelled RNA were bound to the column in the case of types Asia 1 and 0,
      respectively. Possible correlation between the poly(A) tail length, accessibility
      of the genome to nucleases and thermostability of the infective virus is
      discussed. A positive correlation between the thermostability of the genome and
      general distribution of a particular virus type seems to exist. A stable genome
      associated with poor virus immunogenicity may be responsible for the prevalence
      of FMDV type 0 in the nature. The isoelectric focussing of structural proteins
      isolated from the virus samples incubated at 37 degrees C revealed charge
      differences in the major immunogen between the two FMDV types. A rapid
      proteolytic degradation of the viral immunogen and stability of the genome may be
      responsible for frequent outbreaks of FMD, at least, in the endemic countries.

PMID- 8886093
TI  - Determination of the DNA target sequence of poorly reactivable strain HSZP of
      herpes simplex virus type 1 by polymerase chain reaction.
AB  - HSZP strain of herpes simplex virus type 1 (HSV-1)-unlike strains KOS, SC16 and
      ANGpath-established latency in the homolateral trigeminal ganglion of mice at a
      limited rate (21%) when tested by reactivation of latent virus in culture. If a
      nested polymerase chain reaction (PCR) for virus DNA detection was used, the
      positivity rate was 63-100%. The detection rate of HSZP DNA in acutely infected
      gangla did not differ from that of SC16 DNA provided that the sensitivity of PCR
      was below 20 pg of HSZP DNA per 0.5 microgram of total ganglionic DNA. The nested
      PCR assessed at least 200 fg of HSZP DNA per 0.5 microgram of ganglionic DNA.

PMID- 8886095
TI  - Type 2 poliovirus recombinants isolated from vaccine-associated cases and from
      healthy contacts in Brazil.
AB  - In a previous study (Friedrich et al., 1995b) P2/Sabin-derived strains isloated
      in Brazil from vaccine-associated paralytic poliomyelitis (VAPP) cases and from
      healthy contacts were analyzed for the presence of mutations at nucleotide (nt)
      481 in the 5'-noncoding region (5'NCR) and at the codon of amino acid (aa) 143 of
      the capsid protein VP1, that are known to increase neurovirulence. In the present
      study a part of the 3Dpol-coding region of these strains was sequenced (3Dpol
      seq.) with the aim to find recombinant strains. In the 3Dpol seq., four out of
      ten strains isolated from VAPP cases turned out to be recombinants: one had 3Dpol
      seq. from the P1/Sabin strain, while the second had a part of 3Dpol seq. both
      from the P2/Sabin and P1/Sabin strains; the third and fourth recombinants had
      3Dpol seq. from non-vaccine strains. The strains isolated from healthy contacts
      of the two VAPP cases, from which type 2 vaccine/non-vaccine recombinant strains
      were isolated, also consisted from recombinant genomes with the same nt sequences
      as those of the isolates from VAPP cases, confirming the transmission of P2/Sabin
      derived recombinants. Comparison of the aa sequence of the viral RNA polymerase
      of the P2/Sabin strain with the predicted aa sequences of these recombinants in
      3Dopl seq. demonstrated that an aa 69 (Asp-->Glu)) substitution was observed in
      most of the recombinant genomes, while an aa 113 (Thr-->Ser) substitution was
      observed in all the recombinant genomes. The possibility that the genomic
      recombination increased the neurovirulence of these strains cannot be excluded.

PMID- 8886094
TI  - Partial antigenic characterization of potato virus S (Andean strain) by
      monoclonal antibodies.
AB  - Four mouse monoclonal antibodies (MoAbs)) against potato virus S Andean strain
      (PVSA) were tested. While MoAbs 2 and 3 reacted only with complete virions and
      were apparently specific for epitopes dependent on quaternary structure, MoAbs 1
      and 4 appared to be conformation independent and reacted with exposed regions on
      native virions as well as on the surface of dissociated coat protein subunits.
      This seems to be an evidence of metatope existence. The results of competitive
      binding tests together with reaction patterns of individual MoAbs suggest that
      the used MoAbs reacted with at least two different epitopes on PVSA particles or
      polypeptide subunits. Immunoblot analysis of proteolytically cleaved PVSA capsid
      protein (CP) confirmed close proximity of epitopes recognized by MoAbs 1 and 4.
      Anti-PVS polyclonal antibody recognized both intact CP and its natural or
      artificial digest, while the MoAbs bound to intact CP only. These results
      indicate that the surface virus-specific epitopes are located near the terminus
      of CP molecule as it is characteristic for potyviruses.

PMID- 8886096
TI  - Inhibition of hepatitis B virus in vitro by antisense oligonucleotides.
AB  - A series of antisense phosphorothioate oligodeoxynucleotides against hepatitis B
      virus (HBV) were synthesized and evaluated for their antiviral effect in Hep-G2
      cells transfected with HBV genome. The inhibitory effect of the tested antisense
      oligonucleotides was sequence-specific, dose-and time-dependent, and synergistic
      for certain combinations. In virus-inhibitory concentrations the oligonucleotides
      were harmless to 2.2.15 cells. The most effective antisense oligonucleotides were
      found directed against the HBV mRNA transcribed from the cap site of SP II
      promoter, the portion of polyadenylation signal and the initiation region of gene
      S, with an inhibition of the HBsAg and HBeAg production by 85-95% and 50- 60%,
      respectively. To our surprise, antisense oligonucleotides directed against three
      key sites of HBV X gene blocked the expression of HBsAg, HBeAg and HBxAg. This
      fact might be related to the trans-activation of HBV X protein. Using
      radioisotope labelling, we demonstrated that Lipofectin promoted the cellular
      uptake and antiviral effect of antisense oligomers in 2.2.15 cells. These results
      suggest a therapeutic potential of antisense oligonucleotides in the treatment of
      patients chronically infected with HBV.

PMID- 8886097
TI  - Effect of immunosuppression on Balb/c mice infected with murine herpesvirus.
AB  - Balb/c mice were infected with murine herpesvirus (MHV-72) and subjected to
      immunosuppression (IS) with the antibiotic FK506 either during the acute or
      chronic phase of infection. Attempts to detect virus in various organs of
      immunosuppressed and non-immunosuppressed mice at different time interval were
      made. In the mice immunosuppressed on days 3-23 p.i. of the acute phase of
      infection virus was detected in various tested organs and tissues at 2.0 times
      higher rate than those of control mice. At later intervals of the acute phase of
      infection (56-84 days p.i.) virus was still recovered in bone marrow and lymph
      nodes peritoneal cells of immunosuppressed mice, but not in those of control
      animals. In the chronically infected mice immunosuppressed on days 290-320 p.i.,
      the virus was detected in lungs, thymus, bone marrow, spleen and peritoneal cells
      at 3.5 times higher rate than in those of control mice.

PMID- 8886098
TI  - Adaptation of caprinised rinderpest virus to grow in Vero cells in vitro.
AB  - Caprinised rinderpest virus GTV strain (GTV) was adapted to grow in Vero cells
      (vGTV) by polyethylene glycol-mediated fusion of infected goat spleenocytes with
      non-infected Vero cells. The usual methods of infection of cell culture, i.e.
      virus adsorption or co-cultivation, were not successful. vGTV-induced cytopathic
      changes in Vero cells were similar to those reported for rinderpest virus. Virus
      titers increased with the passage number but the virulence for goats decreased.
      Immunoblot analysis did not reveal any difference between vGTV and vRBOK, the
      tissue culture rinderprest virus RBOK strain adapted to Vero cells.

PMID- 8886099
TI  - Phylogenetic analysis of pestivirus based on the 5'-untranslated region.
AB  - A phylogenetic tree of pestiviruses constructed by analyzing their 5'
      untranslated region (UTR) indicated that the genetic relatedness between border
      disease virus and hog cholera virus is much closer than that between genotypes of
      various bovine diarrhoea viruses. This suggests that these viruses are host
      variants within a single species, which can be distinguished by comparison of
      secondary structures at three variable loci in the 5'-UTR.

PMID- 8886101
TI  - First findings of plum pox virus in walnut trees (Juglans Regia L.)
AB  - Plum pox virus (PPV) was transmitted from infected buds and leaves of walnut tree
      (Juglans regia L.) on the following herbaceous indicators: Chenopodium foetidum
      Schrad., Nicotiana bigelovii var. quadrivalvis Fuchs., N. clevelandii x N.
      glutinosa. A positive ELISA reaction with antisera against PPV was obtained from
      infected buds and leaves of Juglans regia L. and from attacked leaves of
      indicator plants.

PMID- 8886100
TI  - Improved method of isolation of Coxiella burnetii proteins.
AB  - An improved method of isolation of Coxiella burnetti proteins was developed. It
      consists of a combination of detergent (sodium dodecyl sulphate (SDS) or sodium
      deoxycholate (DOC) and hot phenol treatments. The resulting phenol phase (PP)
      contained either lipopolysaccharide-(LPS) free proteins (DOC extraction) or
      proteins contaminated with LPS (SDS extraction), while the water phase (WP)
      contained LPS. Isolated C. burnetii proteins induced in mice and rabbits
      antibodies reacting in immunoblot analysis with both phase I and II C. burnetii
      corpuscles. A rabbit serum against C. burnetii prepared by DOC-phenol extraction
      did not react with purified I C. burnetii LPS in immunoblot analysis.

PMID- 8886102
TI  - Belgian neurology: the past, the present and the future.

PMID- 8886103
TI  - The immune system in neurologic disease: selected recent developments.

PMID- 8886104
TI  - Mapping human memory--a brief review.

PMID- 8886105
TI  - Neurophysiological aspects of voluntary movements.

PMID- 8886107
TI  - Aging, disease and death of nerve cells.

PMID- 8886106
TI  - Neurotrophic factors: past and future.

PMID- 8886108
TI  - Multiple sclerosis. A historical review with emphasis on the last 20 years.

PMID- 8886109
TI  - Evidence for chronic ischaemia in the pathogenesis of vascular dementia: from
      neuroPATH to neuroPET.
AB  - Vascular dementia is actually considered as a ill-defined entity. The clinical
      and neuropathologic criteria of this multifactorial disorder remain uncertain.
      Although not widely accepted, the introduction of the concept of incomplete
      infarction in the brain can help to explain some particular types of vascular
      dementia. In the hypoxic-hypoperfusion dementia syndromes of cerebral cortex and
      white matter and in lacunar state dementia, which are the most common types of
      vascular dementia, areas of incomplete infarction co-exist with regions of
      complete infarction. Although initially rejected by early positron emission
      tomographic studies, it can now be demonstrated that these incomplete infarction
      areas reflect chronic ischaemia of the brain and that they are relevant to the
      pathogenesis of vascular dementia.

PMID- 8886110
TI  - Neuro-oncology.

PMID- 8886111
TI  - Hereditary disorders of the nervous system from anatomo-clinical studies to
      molecular biology.
AB  - Hereditary disorders of the nervous system have been defined in the past by their
      main clinical and neuropathological features. The genetic approach has evolved
      from the traditional collection of pedigrees to molecular biology techniques
      which nowadays identify the responsible genes, recognize their defects and
      describe the gene products. We illustrate these changes by a few examples from
      the group of spinocerebellar atrophies, hereditary motor and sensory neuropathies
      and Alzheimer's disease. Modern neurology has found in molecular biology an
      extremely powerful tool to study the hereditary disorders of the nervous system.

PMID- 8886112
TI  - Anterior cingulate dysfunction in presenile dementia due to progressive
      supranuclear palsy.
AB  - We report neuropsychological and neuroimaging investigations performed in a
      patient suffering from presenile onset degenerative dementia and subsequent mild
      extrapyramidal and pyramidal signs. Early neuropsychological testing revealed
      frontal lobe dysfunction. Neuroanatomical pictures were not contributive. After
      four years of evolution, the clinical pattern was consistent with progressive
      supranuclear palsy. Statistical parametric mapping analysis of functional imaging
      revealed a highly significant metabolic impairment in the anterior cingulate
      gyrus, that might be a key feature of subcortico-frontal dementia in progressive
      supranuclear palsy.

PMID- 8886113
TI  - Clinical importance of assessment of anti-HCV IgM antibodies in chronic hepatitis
      C.
AB  - In the majority of patients with acute hepatitis C the anti-HCV IgM antibodies in
      serum were present, however, some patients with chronic hepatitis C were positive
      for anti-HCV IgM too. The aim of this study was to assess the presence of anti
      c22 IgM in patients with chronic hepatitis C and to determine whether the
      positivity for anti-c22 IgM has an impact on the histological finding in the
      liver. A total of 88 patients were examined (44 women, 44 men), mean age 48
      years. The first group comprised 24 patients positive for both anti-HCV IgG and
      anti-c22 IgM, the second group 38 patients positive for anti-HCV IgG only, and
      the third group 26 patients negative for both anti-HCV IgG and anti-c22 IgM. Of
      62 anti-HCV-IgG-positive subjects 24 (39%) were positive also for anti-c22 IgM.
      Of 24 patients who received a blood transfusion 9 (37.5%) were positive for anti
      c22 IgM. The mean serum alanine aminotransferase (ALT) activity was significantly
      higher in subjects with anti-c22 IgM than that in subjects without them (p =
      0.006), however, the difference in aspartate aminotransferase (AST) was not
      significant (p = 0.09). Histological examination was performed in 46 patients.
      Two-thirds of the patients with anti-c22 IgM had either cirrhosis or chronic
      active hepatitis (CAH) while only one third of the anti-HCV-positive patients
      without anti-c22 IgM had CAH or cirrhosis. The results showed that approximately
      40% of the patients with CAH and cirrhosis had anti-c22 IgM, a significantly
      higher serum ALT activity and more serious histological finding in the liver than
      anti-HCV-positive patients without anti-c22 IgM.

PMID- 8886114
TI  - Immunodetection of beet necrotic yellow vein virus RNA3-encoded protein in
      different host plants and tissues.
AB  - The protein p25 open reading frame (ORF) of beet necrotic yellow vein virus-BNYVV
      RNA3 was cloned into bacterial expression vector downstream of the 5-'terminus
      part of beta-galactosidase ORF and the expressed p25 fusion protein was used to
      produce an antiserum. The latter was employed to detect the subcellular location
      of p25 in mechanically inoculated Tetragonia expansa, Chenopodium quinoa and
      sugarbeet leaves by Western blot assay. The results showed that p25 was present
      as a soluble protein only in the S30 fraction of T. expansa, C. quinoa and
      sugarbeet leaves infected with BNYVV.

PMID- 8886115
TI  - Partial inhibition of yellow fever virus replication in vitro with different
      phosphorothioate oligodeoxyribonucleotides.
AB  - Phosphorothioate oligodeoxyribonucleotides targeted to different regions of the
      viral genome were synthesized and used in two kinds of experiments testing their
      activity against yellow fever virus (YFV) replication in cultured cells. We found
      that oligonucleotides complementary to the 3'-end or to the coding region of the
      viral RNA were regularly active in plaque reduction assay, although with
      inconstant efficiency. Oligonucleotides targeted to the 5'-end or to the
      initiation codon region exhibited lesser activity. Homologous oligonucleotides
      targeted to dengue virus RNA had no detectable inhibitory activity against dengue
      virus replication. However, in YFV production reduction assay, a non-specific
      inhibitory activity of a random oligonucleotide was observed. Taken as a whole,
      our results indicate that flaviviruses present detectable but heterogeneous
      sensitivity to phosphorothioate inhibition. Possible explanations are discussed.

PMID- 8886116
TI  - V-myb oncogene and c-myb proto-oncogene expression in avian cells: morphological
      changes of the cells and topographic localization of myb proteins.
AB  - Morphological changes of avian cells expressing the v-myb oncogene or c-myb proto
      oncogene were studied by means of electron microscopy. Expression of both genes
      lead to distinct morphological changes of these cells. The nucleus of LSCC-BM2
      cells espressing v-myb gene was of normal size but usually of irregular shape. It
      contained large unravelled nucleoli with typical interstices in some cells. Small
      nucleolar structures were also localized in the periphery of nuclear membrane.
      Nuclear envelope revealed reduced perinuclear space between two membranes. LSCC
      BK3 cells expressing the c-myb gene were characterized by distinctly enlarged
      nucleus, in most cases of irregular shape. It contained only one nucleolus
      markedly enlarged, often unravelled, with apparent interstitial area. Nucleoli
      with nucleolonemas were observed in some cells. Nuclear envelope formed by two
      obscure membranes showed reduced perinuclear space. Topographic localization of v
      Myb and c-Myb protein products was not basically different, both being detected
      in the nucleus of avian cells. v-Myb and c-Myb markers were distributed mostly in
      clusters, usually associated with interchromatin granules, but some marker was
      associated also with the nuclear membrane. Both Myb products were never detected
      in nucleolar structures of avian cells. Morphological changes of avian cells
      expressing myb genes and topographic localization of Myb proteins in these cells
      were different from those found in the insect cells expressing myb genes. The
      observed differences are discussed.

PMID- 8886117
TI  - Changes in spleen and thymus cell phenotypes in mice vaccinated with the Coxiella
      burnetii phase I whole-cell vaccine or the chloroform-methanol residue subunit
      vaccine.
AB  - Lymphoid cell phenotypes within the spleen and thymus were analyzed to determine
      whether numerical or proportional changes in cell populations could account for
      the immunosuppression seen after vaccination of mice with inactivated phase I
      Coxiella burnetii whole-cell vaccine (WCI). Within 21 days of vaccination with
      WCI, there was a reduction in the percentage of splenic T cells and B cells while
      the numbers of thymic T cells and B cells increased. A substantial percentage of
      spleen cells did not bear typical T cell or B cell surface markers. In contrast,
      except for an early rise (by day 3) in the numbers of T and B cells, injecting
      the chloroform-methanol residue subunit-vaccine (CMR) caused no significant
      phenotypic changes of lymphoid cells in the spleen or thymus. The percentage of
      thymus cells bearing T cell phenotypes was similar in mice vaccinated with WCI or
      CMR. However, the total number of T cells in the thymus dramatically decreased in
      mice vaccinated with WCI. There was no correlation between the lymphocyte
      hyporesponsiveness to mitogens and WCI in vitro and the increased numbers of CD8
      positive splenocytes. These results suggest that WCI vaccination caused dramatic
      changes in splenocyte and thymocyte lymphocyte populations and provide evidence
      for the more benign nature of the CMR vaccine.

PMID- 8886118
TI  - Evaluation of latex agglutination test for rapid detection of goat poxvirus
      antigen and antibodies.
AB  - Soluble antigen fraction of goat poxvirus (GPV) separated from infectious viral
      particles by ultracentrifugation of skin scab suspensions prepared from
      experimentally infected goats was employed for the first time to diagnose goat
      pox. The antiserum raised against this fraction was found to be specific and not
      reactive with healthy goat skin extracts. Subsequently, a latex agglutination
      (LA) test has been developed and standardized for the rapid detection of GPV
      antigen or antibody in skin scab suspensions or serum samples, respectively. In
      comparison to the counter immunoelectrophoresis (CIE) test the LA test was more
      sensitive in the detection of GPV antibodies, but equally sensitive in the
      detection of GPV antigen. The LA test can be taken for a simple and quick
      diagnostic tool for primary screening of goat pox.

PMID- 8886119
TI  - Diagnostic importance of heterophile antibodies and immunoglobulins IgA, IgE, IgM
      and low-avidity IgG against Epstein-Barr virus capsid antigen in children.
AB  - The use of several serological markers in diagnostics of acute Epstein-Barr virus
      (EBV) infection in children and adolescents is recommended. We investigated the
      sera of 299 individuals with clinically suspect infectious mononucleosis for
      heterophile antibodies and EBV viral capsid antigen (VCA)-specific
      immunoglobulins IgA, IgE, IgM and low-avidity IgG. Heterophile antibodies were
      positive in 26%, VCA-specific IgA in 30%, IgE in 35%, IgM in 32% and low-avidity
      IgG in 37% of cases. The acute EBV infection defined as a case having either
      positive IgM or heterophile antibodies was present in 40% of persons. Compared
      with regard to this criterion the sensitivity, specificity, and positive and
      negative predictive values of individual tests were as follows: heterophile
      antibodies-66, 100, 100 and 82%; IgA-53, 84, 69 and 73%; IgE-54, 78, 62 and 72%;
      IgM-81, 100, 100 and 89% low-avidity IgG-66, 82, 71 and 78%. All markers except
      heterophile antibodies were positive even infants aged below 2 years. We consider
      the detection of low-avidity IgG and VCA-specific IgE an useful adjunct for the
      diagnostics of acute EBV infection in children.

PMID- 8886120
TI  - Partial genomic sequence determination of yellow fever virus strain associated
      with a recent epidemic in Gabon.
AB  - A limited epidemic, with important mortality among the initial human cases,
      occured in a forest region in the north of Gabon by the end of 1994. It was
      identified as yellow fever according to first serological and reverse
      transcription/polymerase chain reaction (RT-PCR) results, but no virus was
      isolated. We received 37 sera from people who lived in the same region and
      presented symptoms of the disease during the period of concern. In ten of them,
      we were able to detect and identify yellow fever virus (YFV) RNA by RT-PCR and
      endonuclease digestion of the RT-PCR products. Nucleotide (nt) sequence of two
      regions (242 and 161 nt long) of YFV RNA was determined for three sera. As it
      differed from that of the Asibi strain of YFV, the presence of a new topotype
      (strain) of YFV is presumed.

PMID- 8886121
TI  - Progress in diagnosis of viral hepatitis A, B, C, D and E.

PMID- 8886122
TI  - Chemoprevention of lung cancer by isothiocyanates.
AB  - Naturally occurring and synthetic isothiocyanates are among the most effective
      chemopreventive agents known. A wide variety of isothiocyanates prevent cancer of
      various tissues including the rat lung, mammary gland, esophagus, liver, small
      intestine, colon, and bladder. Mechanistic studies have shown that the
      chemopreventive activity of isothiocyanates is due to favorable modification of
      Phase I and Phase II carcinogen metabolism, resulting in increased carcinogen
      excretion or detoxification and decreased carcinogen DNA interactions. In the
      majority of studies reported, the isothiocyanate must be present at the time of
      carcinogen exposure in order to observe inhibition of tumorigenesis. Our studies
      have focused on the naturally occurring isothiocyanates phenethyl isothiocyanate
      (PEITC) and benzyl isothiocyanate (BITC) as inhibitors of lung cancer. The
      carcinogens employed in these studies have been the major lung carcinogens in
      tobacco smoke- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and
      benzo[a]pyrene (BaP). Combinations of chemopreventive agents that inhibit
      tumorigenesis by NNK and BaP in rodents may be effective in addicted smokers.
      PEITC is an effective inhibitor of lung tumor induction by NNK in F-344 rats and
      A/J mice. BITC but not PEITC inhibits BaP induced lung tumorigenesis in A/J mice.
      PEITC is a selective inhibitor of the metabolic activation of NNK in the rodent
      lung, and studies in smokers who consumed watercress, a source of PEITC, indicate
      that the metabolic activation of NNK is also inhibited by PEITC in humans.
      Combinations of chemopreventive agents active against different carcinogens in
      tobacco smoke may be useful in the chemoprevention of lung cancer.

PMID- 8886123
TI  - Isothiocyanates as inhibitors of esophageal cancer.

PMID- 8886124
TI  - Plant phenolics as potential cancer prevention agents.
AB  - The frequent consumption of fresh fruits and vegetables is associated with a
      lower cancer incidence in humans, and in experimental carcinogenesis. There are
      several groups of substances in plant foods which may contribute to this
      inhibition of tumor development. Almost all fresh fruits, vegetables and cereal
      grains contain appreciable amounts of naturally occurring plant phenolics. A
      brief overview will be presented of the most common plant phenolics in human
      foods and their chemical and biochemical properties. Plant phenolics, originally
      hypothesized to inhibit mutagenesis and/or carcinogenesis by virtue of
      antioxidant or electrophile trapping mechanisms, can also act as potent
      modulators of arachidonic metabolism cascade pathways. Certain plant phenols can
      be effective inhibitors of chemical mutagens, in vitro, and/or carcinogenesis in
      vivo. The historical origins, hypotheses of actions, current status and potential
      adverse effects of the utility of plant phenolics to reduce risk of cancer are
      discussed, as well as future possibilities and needs and objectives for future
      research.

PMID- 8886125
TI  - Cancer chemoprevention by polyphenols in green tea and artichoke.

PMID- 8886126
TI  - Effects of tea on carcinogenesis in animal models and humans.

PMID- 8886127
TI  - Estrogens, phytoestrogens, and breast cancer.

PMID- 8886128
TI  - Soy isoflavonoids and cancer prevention. Underlying biochemical and
      pharmacological issues.
AB  - The isoflavonoids in soy, genistein and daidzein, have been proposed to
      contribute an important part of the anti-cancer effect of soy. Although there
      have been many interesting studies on the effects of isoflavones on biochemical
      targets in tissue culture experiments, in most cases the concentrations used by
      investigators have exceeded 10 microM. However, based on simple pharmacokinetic
      calculations involving daily intake of isoflavones, absorption from the gut,
      distribution to peripheral tissues, and excretion, it is unlikely that blood
      isoflavone concentrations even in high soy consumers could be greater than 1-5
      microM. Experiments designed to evaluate these pharmacological principles were
      carried out in anesthetized rats with indwelling biliary catheters and in human
      volunteers consuming soy beverages. The data from these experiments indicate that
      genistein is efficiently absorbed from the gut, taken up by the liver and
      excreted in the bile as its 7-O-beta-glucuronide. Re-infused genistein 7-O-beta
      glucuronide was also well absorbed from the gut, although this occurred in the
      distal small intestine. In human subjects fed a soy beverage for a period of two
      weeks, plasma levels of genistein and daidzein, determined by HPLC-mass
      spectrometry, ranged from 0.55-0.86 microM, mostly as glucuronide and sulfate
      conjugates. In summary, genistein is well absorbed from the small intestine and
      undergoes an enterohepatic circulation. Although the plasma genistein levels
      achievable with soy food feeding are unlikely to be sufficient to inhibit the
      growth of mature, established breast cancer cells by chemotherapeutic-like
      mechanisms, these levels are sufficient to regulate the proliferation of
      epithelial cells in the breast and thereby may cause a chemopreventive effect.

PMID- 8886129
TI  - Quercetin as a modulator of the cellular neoplastic phenotype. Effects on the
      expression of mutated H-ras and p53 in rodent and human cells.

PMID- 8886130
TI  - Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and
      its hepatic "metastases" in vivo.
AB  - Tumors derived from the colonic epithelium exhibit cholesterol metabolism which
      is clearly different from that in fibroblasts, hepatocytes, adrenals, and
      ovaries. In hepatocytes and fibroblasts MEV inhibition of the rate limiting step
      in cholesterol synthesis HMG Co A reductase can be overcome by the uptake of LDL.
      Colon cancer cells however do not overcome MEV inhibition by LDL uptake but
      rather exhibit further growth suppression Mevinolin (Mevacor), a drug used to
      lower serum cholesterol levels has the advantage of accumulating in the liver to
      approximately 95% with the first pass. A small but variable percentage of non
      sterol precursors may escape inhibition and be utilized for other pathways in the
      isoprenylation of certain proteins, among them members of the ras family. Mutated
      ras, an oncogene, is found in 40-50% of colon tumors and the expression of a
      functional gene product is dependent on isoprenylation for anchorage to the tumor
      cell membrane. d-Limonene, a relatively non-toxic monoterpene found in orange
      skin oil, selectively inhibits isoprenylation and also accumulates to some extent
      in the liver. It was hypothesized that the differences in mevalonate metabolism
      between hepatocytes and colon tumor cells could provide a chemotherapeutic
      advantage in which MEV and/or d-limonene could effectively inhibit cholesterol
      synthesis and post-translational modification of proteins with non-sterol
      cholesterol precursors in colon tumor derived hepatic metastases and thus inhibit
      their growth. Since each drug affects aspects of mevalonate synthesis at
      different points, the effects of the combination of their agents on inhibiting
      tumor metastases was investigated to ascertain if these could be additive. In
      tissue culture, MEV and d-limonene significantly inhibited the growth of CT-26, a
      murine transplantable colon tumor. Cholesterol synthesis assessed in these cells
      indicated that in lipid deficient media the following additions-25
      hydroxycholesterol, and LDL significantly reduced cholesterol synthesis.
      Conversely, perillyl alcohol increased cholesterol synthesis 2.5 fold. In cells
      cultured in FBS based medium, which have an FBS control, MEV treatment reduced
      cholesterol synthesis to 65% of control. Perillyl alcohol increased synthesis 1.4
      fold and when given in conjunction with MEV, it abolished the effects of this
      inhibitor. In isoprenylation studies of 14C-mevalonate incorporation into
      proteins, MEV impaired isoprenylation by restricting synthesis of mevalonate
      derived intermediates. Results of CT-26 treatment with perillyl alcohol are
      inconsistent with its putative role as a protein isoprenylation inhibitor. The
      combination of these agents indicates an additive action which requires
      additional investigation to elucidate their mechanism(s). Dietary MEV and d
      limonene were evaluated alone and in combination for their chemotherapeutic
      potential in a hepatic "metastasis" model. Using splenic colonization in which CT
      26 was implanted into the spleen and ultimately seeded the liver, each of these
      compounds were found to inhibit the growth of resultant tumors both alone and in
      combination by approximately 80% versus controls at 35 days post-implantation.
      Assessment of HMGCoA reductase in liver and tumor indicated that these agents
      were effective in reaching these target sites. The findings to date indicate that
      while d-limonene and MEV may differentially affect the same pathway, and their
      individual actions may appear antagonistic in vitro, their overall action
      individually or together, appears promising as a chemotherapeutic modality for
      the possible management of hepatic metastases from colon cancer.

PMID- 8886131
TI  - Antitumorigenic effects of limonene and perillyl alcohol against pancreatic and
      breast cancer.
AB  - Perillyl alcohol is a natural product from cherries and other edible plants.
      Perillyl alcohol and d-limonene, a closely related dietary monoterpene, have
      chemotherapeutic activity against pancreatic, mammary, and prostatic tumors. In
      addition, perillyl alcohol, limonene, and other dietary monoterpenes have
      chemopreventive activity. Several mechanisms may account for the antitumorigenic
      effects of monoterpenes. For example, many monoterpenes inhibit the post
      translational isoprenylation of cell growth-regulatory proteins such as Ras.
      Perillyl alcohol induces apoptosis without affecting the rate of DNA synthesis in
      both liver and pancreatic tumor cells. In addition, monoterpene-treated,
      regressing rat mammary tumors exhibit increased expression of transforming growth
      factor beta concomitant with tumor remodeling/redifferentiation to a more benign
      phenotype. Monoterpenes are effective, nontoxic dietary antitumor agents which
      act through a variety of mechanisms of action and hold promise as a novel class
      of antitumor drugs for human cancer.

PMID- 8886132
TI  - Monoterpenes as regulators of malignant cell proliferation.
AB  - Limonene and related monoterpenes display compelling anticarcinogenic activity.
      The mechanism(s) that underline this activity is/are as yet unknown. One
      attractive possibility is that the monoterpenes interact with the RAS signal
      transduction pathway. The monoterpenes have been shown to impair incorporation of
      mevalonic acid-derived isoprene compounds, that is farnesyl pyrophosphate, into
      RAS and RAS-related proteins. As farnesylation is critical for RAS's membrane
      localization and function, the isoprenylation pathways have received attention as
      potential targets of anti-RAS pharmacological maneuvers. We have expanded on
      prior studies and demonstrate that one of limonene's metabolic derivatives,
      perillyl alcohol, decreases the levels of antigenic RAS in the human-derived
      myeloid THP-1 and lymphoid RPMI-8402 leukemia cell lines. Both limonene and
      perillyl alcohol decrease levels of 35[S] methionine labeled RAS proteins in
      cells that have been pulsed with radiolabeled methionine for four hours. In
      contrast, lovastatin, which inhibits hydroxymethylglutaryl coenzyme A reductase
      and thus depletes cells of farnesyl pyrophosphate, does not diminish levels of
      total antigenic RAS but rather results in a shift in the RAS protein; levels of
      farnesylated RAS decrease whereas levels of unmodified/unfarnesylated RAS
      increase. As limonene and perillyl alcohol do not induce such a shift we conclude
      that these monoterpenes decrease farnesylated RAS protein levels by a mechanism
      that is clearly distinct from that of either depleting cells of farnesyl
      pyrophosphate or inhibiting the enzyme farnesyl protein transferase that
      catalyzes the posttranslational farnesylation of RAS. These findings are
      discussed with respect to implications for the monoterpenes to alter RAS protein
      synthesis and degradation. The results of these studies will likely impact the
      inclusion of the monoterpenes in clinical anticancer trials.

PMID- 8886133
TI  - Organosulfur compounds and cancer.
AB  - There is evidence that organosulfur compounds can inhibit the induction and
      growth of cancer. Several organosulfur compounds are dietary constituents and
      Allium species are a rich source of such molecules. Some but not all
      epidemiological studies have suggested that consumption of garlic can decrease
      cancer incidence. There is substantial evidence that constituents of garlic
      including diallyl sulfides can inhibit the induction of cancer in experimental
      animals. Effects on both tumor initiation and promotion have been documented.
      Some effects may be mediated by modulation of carcinogen metabolism involving
      altered ratios of phase I and phase II drug metabolizing enzymes. 59,60
      Inhibitory actions on the growth of tumor cells have been documented and, for
      some tumor cells, differentiating effects of diallyl sulfides can occur. A
      definitive mechanism of action has not been established and evidence exists for
      effects at several sites in carcinogen metabolism and regulation of tumor growth.
      It is not always clear that laboratory studies can be extrapolated to reasonable
      levels of consumption by humans of garlic or other Allium species.

PMID- 8886134
TI  - Recent results in the organosulfur and organoselenium chemistry of genus Allium
      and Brassica plants. Relevance for cancer prevention.

PMID- 8886135
TI  - Allium vegetables and the potential for chemoprevention of cancer.

PMID- 8886136
TI  - The attributes of selenium-enriched garlic in cancer prevention.

PMID- 8886137
TI  - Is there a need to change the American diet?

PMID- 8886138
TI  - The National 5 A Day for Better Health Program.

PMID- 8886139
TI  - Nutritional implications of dietary phytochemicals.
AB  - Although increasing the levels of phytochemicals in foods via traditional
      breeding or genetic engineering would appear to pose less of a risk, there is
      still the possibility of over consumption given the ease with which phytochemical
      content can be increased. According to the recent position paper by the American
      Dietetic Association on phytochemicals, "the dietetics professional ... is the
      specialist who should make recommendations concerning appropriate dietary intake
      to optimize the potential benefits of phytochemical-rich or functional foods in
      overall health." For dietitians to make these recommendations, it will be
      necessary for the nutrition community to make a concerted effort to incorporate
      information on phytochemicals into nutrition manuals and professional resources.
      As it is, most of the research and discussion of phytochemicals is conducted by
      professionals not related or only peripherally related to the field of nutrition.
      This is truly an exciting time to be involved in the nutrition field. We have
      moved a head from thinking that only a relatively small number of dietary factors
      possess biological activity to recognizing that there are hundreds and perhaps
      thousands of such factors. It will be many years before our understanding of
      phytochemicals approaches our knowledge of vitamins and minerals- and it is worth
      nothing that our knowledge of vitamins and minerals is still incomplete. But it
      does appear that the phytochemicals help explain why plant-based diets, in
      general, are associated with a reduced risk of many chronic diseases. And in
      fact, his may be the most important outcome from use of phytochemicals. The
      nutrition community now has more reasons for encouraging consumers to eat plant
      based diets.

PMID- 8886140
TI  - Designer foods. Is there a role for supplementation/fortification?

PMID- 8886141
TI  - Wheat bran, colon cancer, and breast cancer. What do we have? What do we need?

PMID- 8886142
TI  - Diet, nutrition, and cancer prevention. Research opportunities, approaches, and
      pitfalls.

PMID- 8886143
TI  - Studies on preventive nephrology: pattern of the subsets of hypertension in the
      paediatric, adolescent and adult population of Gassim, Saudi Arabia.
AB  - As part of our studies in preventive nephrology, we have recorded the casual
      blood pressure during a total population cross-sectional survey of the Faizia
      East Primary Health District (FEPHD). A total of 5671 subjects had adequate
      records. Of these 2222 were adults (> 19 years). The prevalence of systemic
      hypertension (HPN) was calculated, using as cut-off levels, > or = 140/90 for the
      adult population and > or = 95th percentile as recommended by the Task Force for
      Blood Pressure Control in Children (1987) for the paediatric and adolescents (3
      18 years). Using these definitions without modification, the three subsets of HPN
      viz. combined systolic/diastolic (S/DHPN), isolated systolic (ISHPN) and isolated
      diastolic (IDHPN) were derived for each of the age cohorts studied-10-year age
      cohorts for the adults and the Task Force 3-year age cohorts for the
      paediatric/adolescent (P/A) population. In both adult and P/A population ISHPN
      constituted the bulk of the hypertensive population (56.68% for the adults and
      51.57% for P/A). the IDHPN subset was the least for adults making up 11.64% while
      the S/DHPN was in between constituting 31.68%: For the P/A population S/DHPN was
      the least, 15.95% and IDHPN (32.48%) was in between. When distributed into 10
      year age cohorts for the adults, ISHPN showed the steepest gradient depicting
      increasing prevalence with advancing age. On the other hand, IDHPN did not rise
      with age; if at all, it tended to fall. The slope for S/DHPN was sandwiched in
      between. For the P/A population, for all the 3-year age cohorts, and for all the
      three subsets, there was an initial peak in childhood followed by a decline in
      adolescence. However, some variations were discernible in each subset. ISHPN in
      girls peaked at 10-12 before declining but in boys it virtually followed an even
      keel. IDHPN, in both boys and girls peaked sharply at 6-9 before a rapid decline
      in prevalence into adolescence. S/DHPN also peaked at 6-9 but both the upward
      slope and the subsequent decline were more gentle than the other subsets. When
      viewed together for our study population, assuming equivalence in cut-off levels
      for HPN, both ISHPN and S/DHPN seem to exhibit a bimodal curve, with one peak in
      childhood and a second rise in adulthood continuing into old age. IDHPN showed a
      unimodal curve, with the one peak in childhood followed by a continuing decline
      through adolescence into adulthood to virtual disappearance in old age. We
      believe these slopes may have prognostic significance which are not entirely
      clear at the moment but our findings reinforce the importance of the systolic
      blood pressure and that diastolic blood pressure alone should no longer be used
      as the index treatment or complication of high blood pressure.

PMID- 8886144
TI  - Perception of sickle cell haemoglobinopathy among 'would-be' counsellors.
AB  - Fifty-six paramedical personnel in training as Community Health Officers (CHO)
      and Nurse Tutors were interviewed by a self administered questionnaire as to
      personal information and what they know and believed about sickle cell
      haemoglobinopathy. Even after the normal course of lectures on the
      haemoglobinopathies as given for their training as CHO's, many of them still did
      not fully understand the topic as shown by mixed up and confusing answers given
      to questions. As a result of the maturity and exposure as community health
      workers, they are being proposed for retraining as counsellors with regards to
      the haemoglobinopathies. From our findings to this study it appears that using a
      formal lecture schedule would not be adequate in intimating this group with the
      problems they would likely encounter as CHO's in practice. A training programme
      should also include organised group discussions designed to detect biases and
      prejudices and correct them before certification as community health officers.

PMID- 8886145
TI  - Clinico-epidemiological patterns of HIV infection in STD patients in Ibadan.
AB  - The HIV-seropositive subjects identified among the STD Clinic patients seen at a
      Special Treatment Clinic between 1989 and 1990 were studied to determine the
      epidemiological and clinical trends of HIV infection in these patients, and to
      demonstrate any association between the STDs and HIV- seropositivity. Thirty
      seven out of the 581 patients investigated have been confirmed HIV-seropositive
      by Western bolt. The prevalence of HIV infection was 6.4%. Anti-HIV-1 antibody
      prevalence (3.6%) was higher than that of anti-HIV-2 antibody (2.8%). The age
      range of the patients investigated was from 2 weeks to 49 years, and the HIV
      seropositive cases were in the age-range 15-49 years, with peak incidence of HIV
      infection in the 21-30 years age-bracket. The male: female ratio of HIV
      seropositive subjects was practically the same (1.01:1). HIV antibody-positive
      cases consisted of residents from towns in both Northern and Southern Nigeria.
      Only one of the HIV antibody-positive cases has developed clinical AIDS
      progressive weight loss fourteen months after he was found positive for HIV
      antibody.

PMID- 8886146
TI  - The anterior dimensions of the pelvis in male and female Nigerians.
AB  - A retrospective study on the anteroposterior X-ray films of the pelvis of 40
      male, and 31 female Nigerians was undertaken to verify if there was any
      significant difference in the values of the transverse diameter of the inlet
      (TID), bicristal diameter (BCD), bituberal diameter (BTD), and subpubic angle
      (SA) between the male and the female, between the younger age group (21-45 years)
      and the older age group (46-70 years) in each sex, using the student's t-test.
      Results showed that TID, BTD and SA each was significantly greater in the female
      than in the male (P < 0.001). BCD showed no significant difference between the
      sexes (P > 0.05). SA was significantly greater in the older age group than in the
      younger age group (P < 0.05) while the other variable showed no significant
      difference. TID showed significant positive correlation with BCD, and BTD in the
      female (P < 0.05), and with BCD, BTD, and SA in the male (P < 0.05). The value of
      SA in female is obtuse but overlaps between acute and obtuse in males. Ninety
      three per cent of the female pelvis had subpubic angle above the 111.3 degrees
      demarking point (DP) but none of the male or female pelvis was marked out by the
      lower or upper demarking points of BCD, suggesting a relevance of DP of SA in sex
      discrimination. The mean ratio of TID to BTD was 1.5:1 in the male and 1.2:1 in
      the female suggesting a gynaecoid tendency in the latter. This study provided
      data that can be useful for clinical and radiological pelvimetry for use in
      obstetrical care of Nigerian women, and normal values for Nigerian male and
      female.

PMID- 8886147
TI  - Defaecation pattern and intestinal transit in Nigerian children.
AB  - The defaecation pattern and intestinal transit time of 410 apparently healthy
      children aged between 6 months and 5 years were studied by questionnaire and
      carmine red marker. The majority of the children ate a predominantly high residue
      diet. Stool frequency varied from once every other day to 5 times a day, with 95%
      of the children opening their bowels one to three times a day. There was a
      gradual decline in mean stool frequency with increasing age. The stool produced
      was usually soft and between 50 and 75 ml in size. Mean mouth to anus transit
      time in 98 randomly selected children from the study group was 18.3 hours. The
      information obtained from this study should facilitate early identification of
      diarrhoea and constipation in the Nigerian pre-school child.

PMID- 8886148
TI  - Anomaly of the femoral artery passage through the substance of sartorius muscle.
      Clinical consequences.
AB  - The passage of the femoral artery through the substance of the sartorius muscle
      and its clinical consequences are presented. In the series of cadavers studied,
      the incidence of occurrence of this condition is probably less than 0.001% in
      both Caucasians and black Africans. It is suggested that this anomaly which
      rarely occurs is due to the angioblastic column of cells forming the femoral
      artery passing through the myoblastic column of cells forming the sartorius
      muscle.

PMID- 8886149
TI  - Experience with carbimazole in the treatment of the hyperthyroidism of Graves'
      disease in Nigerian patients.
AB  - To estimate the rate of remission and relapse in patients with thyrotoxic Graves'
      disease following therapy with thionamides, the course of 49 patients who were
      treated with carbimazole and followed for a mean (+/-S.D.) of 22.0 +/- 17.8
      months, was analysed. A remission rate of 61% was obtained. Remissions were more
      common in patients with small goiters and those with a short duration of illness.
      Relapse occurred most commonly within the first few months following the
      discontinuation of the drug. Thirty-two per cent of the patients left the clinic
      either before or soon after achieving euthyroidism. It is concluded that the
      thionamides are quite efficacious in the induction of remission in newly
      diagnosed Nigerian patients with toxic Graves' disease and probably should
      presently be the principal treatment modality for these patients, rather than
      subtotal thyroidectomy. Efforts should be made to reduce the frequent drop-out of
      our patients from the clinic during follow-up.

PMID- 8886150
TI  - Antibiogram of bacterial isolates from cases of otitis media and lower
      respiratory tract infections.
AB  - A total of one hundred and two cases of otitis media were screened for the
      isolation of bacterial flora of ears. Out of this, Staphylococcus aureus,
      Streptococcus pneumoniae and Haemophilus influenzae accounting for 41.2%, 25.5%
      and 13.3% respectively were isolated. A further two hundred and four sputum
      samples from cases of lower respiratory tract infections were screened. Moraxella
      catarrhalis, S. aureus, S. pneumoniae and H. influenzae constituting 20.9%, 37%,
      30% and 21% were isolated in that order. Thirty-one point seven percent of the
      Moraxella catarrhalis isolates were beta-lactamase positive. Beta-lactamase M.
      catarrhalis were resistant to penicillin and ampicillin while the non-beta
      lactamase producers were sensitive to these antimicrobial agents. However, both
      beta-lactamase producers and non-producers were resistant to trimethoprim but
      sensitive to erythromycin, tetracycline and amoxycillin. Staphylococcus aureus,
      S. pneumoniae and H. influenzae was also sensitive to penicillin while S.
      pneumoniae was also sensitive to erythromycin and H. influenzae to
      chloramphenicol.

PMID- 8886151
TI  - Comparison of the genome ds RNA of human rotavirus strains shed in parts of
      Ibadan, Nigeria.
AB  - The incidence and genome electropherotypes of human rotavirus detected in a
      hospital and in a community within Ibadan, Nigeria were compared by
      polyacrylamide gel electrophoresis. On the whole, 13% (31/239) rotavirus was
      detected; 14.7% (15/102) from the community and 11.7% (16/137) from the hospital.
      The incidence was significantly higher (P < 0.01) in the community than in the
      hospital. There were 11 (80.0%) long and 3 (20.0%) short forms observed in the
      community, whereas 14 (87.5%) long and 2 (12.5%) short froms were detected in the
      hospital. On co-electrophoresis, however, only 4 and 6 distinct electropherotypes
      were demonstrated in the hospital and the community respectively. Three of these
      were common to both places with 1 and 3 electropherotypes being unique to the
      hospital and the community, respectively.

PMID- 8886152
TI  - An evaluation of the WHO criteria for abnormal glucose tolerance test during
      pregnancy in Nigerian women.
AB  - A 75 g oral glucose tolerance test was performed in 127 normal Nigerian women
      between 24 and 28 weeks of pregnancy. The glucose response at fasting, 1, 2 and 3
      h were studied. At 2 h, the glucose level at 2-SD and 4-SD above the mean were
      less than the criteria of abnormality recommended by the World Health
      Organisation: 6.5 mmol/l vs. 8 mmol/l for impaired glucose tolerance and 8.0
      mmol/l vs. 11.0 mmol/l for gestational diabetes mellitus. The area under the
      glucose response curve correlated best with the glucose levels at 2 h during the
      OGTT (y = 4.3 + 1.8x, r = 0.862). The 75-g OGTT interpreted with the WHO criteria
      appear not to be appropriate for use in pregnant women in Nigeria.

PMID- 8886153
TI  - Pattern of paediatric blood pressure in rural, semi-urban and urban communities
      in Ilorin, Nigeria.
AB  - The blood pressures of 2,526 children aged between 1 and 14 years were measured
      in their home environments in rural, semi-urban and urban communities in Ilorin.
      Blood pressure increased with age, but there was no significant difference
      between the communities. Girls had higher blood pressures than boys between the
      ages of 9 and 13 years, in the semi-urban and rural communities. The prevalence
      of high blood pressure in the urban community (9.5%) was higher, though not
      significantly so, than the rural community (6.3%). It is concluded that the
      prevalence of paediatric high blood pressure in the African is higher than
      previously reported.

PMID- 8886154
TI  - Peak expiratory flow rate in Nigerian school children.
AB  - Peak expiratory flow rate (PEFR) was measured using the Wright's peak flow meter
      in 263 school boys and 275 school girls living in Lagos, Nigeria. Their ages
      ranged from 6.0 years to 19.0 years (mean 11.9 +/- 3.8 yrs. for boys and 11.8 +/-
      3.9 yrs. for girls). Mean PEFR was 359.2 +/- 102.0 L/min (range 160.0-610.0
      L/min) in boys and 327.7 +/- 81.3 L/min (range 160.0-500.0 L/min) in girls. Apart
      from ages 17, 18 and 19, peak expiratory flow rates were similar in both boys and
      girls. In both sexes, PEFR correlated positively and significantly with age,
      height, weight and body surface area. Also in both sexes and in all age groups
      studied, PEFR was significantly higher than predicted values obtained from
      previous Nigerian and caucasian prediction equations. When compared with values
      obtained from a second caucasian prediction equation, observed values were
      significantly higher in the 6-10 years and 16-19 years age groups in boys and 11
      15 years and 16-19 years age groups in girls. New prediction equations for
      calculating PEFR in Nigerian boys and girls are presented. Observed PEFR may be
      due to enhanced stature in Nigerian children resulting from improved environment
      and genetic factors.

PMID- 8886155
TI  - Measles antibodies in the breast milk of nursing mothers.
AB  - A total of 216 breast milk samples collected from nursing mothers and
      corresponding numbers of finger prick sera from their suckling babies were tested
      for measles antibodies. Fifty (22.1%) of the nursing mothers had antibody while
      38 (16.8%) of the sera were positive for measles haemagglutinating (HI)
      antibodies. Forty-one (18.9%) breast milk samples were found to contain measles
      complement fixing (CF) antibody while none of the serum samples from the suckling
      babies had CF antibody. Only 12 of the positive sera were from HI positive
      mothers. Our result suggests that very little level of measles antibody is passed
      through the breast milk.

PMID- 8886156
TI  - Changes in endoplasmic reticulum associated with beta-naphthoflavone-inducible
      cytochrome P450 in murine liver: a quantitative analysis.
AB  - Cytochrome P450s are found associated with membranes of endoplasmic reticulum
      where they catalyse the oxidation and biotransformation of a wide range of
      substances. It is therefore expected that their induction and catalytic
      activities would correlate with the ultrastructure of the cell. In this study, we
      compared the structure of the hepatocytes of C57BL/6 mice at the basal level in
      the untreated control animal, and followed induction with the beta-naphthoflavone
      in the experimental animal. Qualitative analysis of liver sections from control,
      corn oil-treated mice, and the induced, beta-naphthoflavone-treated mice were
      essentially similar with no obvious differences between the two groups. Direct
      morphometry was utilized to quantify the amounts of smooth and rough endoplasmic
      reticulum in the hepatocytes. A computerized Bioquant Image Analysis System was
      used to determine the areas of endoplasmic reticulum in the hepatocytes.
      Morphometric analysis showed 1.004-fold increase in the amount of smooth
      endoplasmic reticulum and 1.018-fold increase in amount of rough endoplasmic
      reticulum following treatment of C57BL/6 mice with beta-naphthoflavone. These
      increases were not significantly different from amounts in control hepatocytes
      (P). In conclusion, induction of cytochrome P450 by beta-naphthoflavone does not
      appear to elicit increased proliferation of the endoplasmic reticulum.

PMID- 8886157
TI  - Detection and localization of CYP1A1/CYP1A2 in murine liver: electrophoresis,
      immunoblotting and immunocytochemistry.
AB  - Multiple forms of cytochrome P450 exist some of which are selectively inducible
      by exposure of the organism to a variety of foreign compounds. In this study, a
      monoclonal antibody specific for 3-methyl-cholanthrene-inducible cytochrome P450,
      Mab 1-7-1, was used to detect, localize and quantify CYP1A1/CYP1A2 in livers of
      C57BL/6 mice. Mab 1-7-1 recognized a faint band in the range between 45-66 Kd in
      Western immunoblots of liver microsomes from control mice, and a strong band in
      the same range, in liver microsomes from beta-naphthoflavone-treated mice.
      Microsome from control liver contained minimal levels of CYP1A1/CYP1A2;
      pretreatment with beta-naphthoflavone caused an increase in their expression.
      Immunoelectron microscopy was used to demonstrate the cellular localization and
      quantification of these isozymes in the liver. The immunolabeling procedure
      confirmed the endoplasmic reticulum as the primary site of CYP1A1/CYP1A2
      induction in hepatocytes. This organelle showed the highest labeling density
      after treatment with beta-naphthoflavone. Increase in CYP1A1/CYP1A2 was 33.4-fold
      by morphometric analysis in induced hepatocytes in comparison to non-induced
      cells. In conclusion, CYP1A1/CYP1A2 is highly induced by beta-naphthoflavone in
      C57BL/6 mouse liver, and the cellular site of expression is the endoplasmic
      reticulum.

PMID- 8886158
TI  - Anaesthetic considerations in exomphalos repair: a report of 2 cases.
AB  - The anaesthetic management of two neonates with exomphalos associated syndromes
      for surgical repair are described. The technical advancements in the surgical and
      anaesthetic management of these neonates which have resulted in reduction in
      morbidity and mortality are discussed. The high incidence of associated anomalies
      and the problems they pose to the anaesthetist in addition to the usual
      challenges of neonatal anaesthesia are highlighted.

PMID- 8886160
TI  - Unipolar relatives in bipolar pedigrees: a search for elusive indicators of
      underlying bipolarity.
AB  - In an effort to identify features indicative of underlying bipolarity within the
      unipolar relatives of bipolar probands, we compared unipolar relatives of
      bipolars with unipolar relatives of controls. Using data from the Yale-NIMH
      Collaborative Study of Depression, we compared a number of demographic and
      clinical features individually, and then developed a logistic regression model
      for the differences found. Unipolar relatives of bipolars were generally similar
      to relatives of controls, but they were older and more likely to suffer from more
      severe, even psychotic, depression, and somewhat less likely to report a brief
      transition into their illness. A multiple logistic regression model for observed
      differences was highly statistically significant, but had limited ability to
      discriminate effectively between the two groups. These findings suggest that more
      stringent diagnostic criteria might be beneficial if unipolar relatives are
      counted as affected in linkage studies of bipolar disorder. The ability of this
      strategy to improve the "clinical phenotype" is limited, however, and other
      approaches may be needed to identify features of underlying bipolarity and thus
      to define "caseness" for unipolar relatives in linkage analyses of bipolar
      disorder.

PMID- 8886159
TI  - Strong linkage disequilibrium and haplotype analysis in Japanese pedigrees with
      Machado-Joseph disease.
AB  - To identify the markers tightly linked to Machado-Joseph disease (MJD) and to
      investigate whether a limited number of ancestral chromosomes are shared by
      Japanese MJD pedigrees, a detailed linkage analysis employing D14S55, D14S48,
      D14S67, D14S291, D14S280, AFM343vf1, D14S81, D14S265, D14S62, and D14S65 was
      performed. The results of multipoint linkage analysis as well as detection of
      critical recombination events indicate that the gene for MJD is localized in a 4
      cM region between D14S280-D14S81. We found strong linkage disequilibria at
      AFM343vf1 and D14S81, and association of a few common haplotypes with MJD. These
      results indicate that there is an obvious founder effect in Japanese MJD and
      suggest the possibility of the existence of predisposing haplotypes which are
      prone to expansions of CAG repeats.

PMID- 8886161
TI  - Assessment of association of D3 dopamine receptor MscI polymorphism with
      schizophrenia: analysis of symptom ratings, family history, age at onset, and
      movement disorders.
AB  - Several studies have reported an association between schizophrenia and
      homozygosity for the MscI restriction site in exon 1 of the D3 dopamine receptor
      gene, but other studies have failed to find this association. Recent reports have
      suggested that the association is most salient in male patients with a family
      history of schizophrenia. We examined this restriction site in a group of
      schizophrenic patients (n = 84) and in normal controls (n = 77). Patients were
      subdivided according to demographic and clinical features, particular attention
      being paid to movement disorders. No significant difference in allelic or
      genotypic distribution was seen between the two groups. No association was seen
      between homozygosity and a positive family history, age at onset of illness,
      clinical subtype, negative symptom score, or movement disorder scores.

PMID- 8886162
TI  - Identification of a missense mutation and several polymorphisms in the
      proenkephalin A gene of schizophrenic patients.
AB  - Schizophrenia is a complex and severe disorder of unknown cause and
      pathophysiology. In this study, we examined the opioid hypothesis for
      schizophrenia at the molecular level, focusing on the dopamine-regulated
      proenkephalin A gene (chromosome 8q11.23-q12). We have screened 150 schizophrenic
      patients for sequence variations within the promoter region, entire coding
      sequence, and 3'-untranslated region. We find one sequence change in a conserved
      amino acid that may be of functional significance. This mutation was found in a
      single schizophrenia patient but not in controls. Although several new, race
      specific polymorphisms were identified, all other sequence changes appeared to be
      common polymorphisms, unlikely to contribute to the etiology of schizophrenia.

PMID- 8886165
TI  - Relationship of sleep abnormalities to patient genotypes in Prader-Willi
      syndrome.
AB  - To assess whether sleep abnormalities are related to the genetic abnormalities in
      Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and
      daytime) and determined the chromosome 15 genotypes in eight patients with PWS.
      Four patients demonstrated sleep onset REM periods (SOREM), and five met the
      objective polysomnographic criteria for severe or moderate excessive daytime
      sleepiness (EDS). Three of the four patients with SOREM displayed a paternally
      derived deletion of chromosome 15q11-q13, whereas the fourth exhibited maternal
      uniparental heterodisomy in this chromosomal region (UPD). Two of the four
      patients that did not display SOREM carried paternally derived deletions; the
      remaining two demonstrated UPD. Four of the five patients with EDS displayed
      paternal deletions, and the fifth exhibited UPD. One of three patients without
      evidence of EDS demonstrated paternal deletion; the remaining two showed UPD.
      Although neither EDS nor SOREM was not consistently associated with a specific
      genetic abnormality, these phenotypes may be more common in patients with
      paternal deletions than in those UPD. Sleep abnormalities in PWS cannot be
      explained by a single genetic model.

PMID- 8886163
TI  - Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with
      the psychiatric manifestations of velo-cardio-facial syndrome.
AB  - Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated
      with typical facial appearance, cleft palate, cardiac defects, and learning
      disabilities. The majority of patients have an interstitial deletion on
      chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric
      illnesses have been reported in patients with VCFS, including schizophrenia,
      bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric
      manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within
      22q11. One candidate that has been mapped to this region is catechol-O
      methyltransferase (COMT). We recently identified a polymorphism in the COMT gene
      that leads to a valine-->methionine substitution at amino acid 158 of the
      membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4
      fold reduction in enzymatic activity, compared with homozygotes for COMT158val.
      We now report that in a population of patients with VCFS, there is an apparent
      association between the low-activity allele, COMT158met, and the development of
      bipolar spectrum disorder, and in particular, a rapid-cycling form.

PMID- 8886164
TI  - Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin
      pairs.
AB  - Research and clinical experience indicate that drug use disorders tend to run in
      families. The objective of this study was to distinguish between the family
      environment and genetic factors as the source of this observed family
      resemblance. Data were collected by telephone interview from members of the
      Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S.
      military between 1965 and 1975. There were 3,372 pairs in which both twins
      participated. Drug use disorder was defined as receiving a diagnosis of drug
      abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or
      been dependent on at least one illicit drug. A significant difference between
      concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a
      genetic influence on drug use disorder. Biometrical modeling indicated that
      genetic factors (34% of the variance), the environment shared by twins (28% of
      the variance), and the nonshared environment (38% of the variance) had
      significant influences of similar magnitudes on the individual's risk of
      developing a drug use disorder. These results support the application of
      molecular genetic approaches to elucidate the genetic influence on drug use
      disorder, as well as the potential efficacy of environmental intervention to
      reduce risk.

PMID- 8886166
TI  - Dopamine DRD2/Cys311 is not associated with chronic schizophrenia.
AB  - A mutation in the DRD2 receptor gene has been reported in association with
      schizophrenia in Japanese and Caucasian populations. The variation, Ser to Cys at
      codon 311, occurs in the third intracellular loop of the receptor and is
      therefore putatively functional. We report the results of screening US Caucasian
      schizophrenic and nonschizophrenic populations. We detected the occurrence of the
      DRD2 Cys311 variant in both schizophrenics and controls. Our data demonstrates no
      significant difference between the frequency of Cys311 in Caucasian schizophrenic
      and non-schizophrenic populations, indicating no association with schizophrenia.

PMID- 8886167
TI  - Nonlinkage of D6S260, a putative schizophrenia locus, to bipolar affective
      disorder.
AB  - To examine whether genes that predispose to schizophrenia also confer a
      predisposition to other psychiatric disorders such as bipolar affective disorder
      (BAD), we tested for linkage between the recently identified schizophrenia
      susceptibility locus D6S260 and the inheritance of BAD in 12 large Australian
      pedigrees. We found no evidence for linkage over a region of 12-27 cM from the
      D6S260 locus, depending on the model used. Our results therefore do not provide
      support for the continuum theory of psychosis.

PMID- 8886168
TI  - Lack of association between TaqI A1 allele of dopamine D2 receptor gene and
      alcohol-use disorders in atayal natives of Taiwan.
AB  - Association studies between the A1 allele of the dopamine D2 receptor (DRD2) gene
      TaqI A polymorphism and alcoholism remain controversial. A recent study from
      Japan demonstrated that the A1 allele is associated with severe alcoholism in the
      Japanese population. We were interested in knowing if this association also
      exists in the Atayals of Taiwan, who were found to have a higher prevalence of
      alcohol-use disorders than the Han Chinese in Taiwan. Genotype and allele
      frequencies were determined in alcohol-abusing, alcohol-dependent, and
      nonalcoholic control Atayal natives in Taiwan. A1 allele frequencies in alcohol
      dependent, alcohol-abusing, and normal control Atayals were 0.39, 0.42, and 0.39,
      respectively. No difference in A1 allele frequency was found among these three
      groups. Our data do not support the hypothesis that the A1 allele of the TaqI A
      polymorphism of the DRD2 gene increases susceptibility to alcohol-use disorders
      in the Atayals of Taiwan.

PMID- 8886169
TI  - Linkage disequilibrium analysis of G-olf alpha (GNAL) in bipolar affective
      disorder.
AB  - This study examines G-olf alpha as a possible candidate gene for susceptibility
      to bipolar affective disorder (BPAD) using the Transmission Disequilibrium Test
      (TDT). G-olf alpha, which encodes a subunit of a G-protein involved in
      intracellular signaling, maps within a region of chromosome 18 that has been
      implicated by two different linkage studies as a potential site of BPAD
      susceptibility loci. The expression pattern of G-olf alpha in the brain, its
      coupling to dopamine receptors, and the effects of lithium salts on G-proteins
      all support G-olf alpha as a candidate gene for BPAD. Our study population
      consisted of 106 probands and sibs with bipolar I disorder, with a median age-at
      onset of 21.5 years ascertained from the United States. There was no evidence of
      linkage disequilibrium between BPAD and any of the observed G-olf alpha alleles
      in our sample. Division of families based on sex of the transmitting parent did
      not significantly change the results. This sample had good power (78%) to detect
      linkage disequilibrium with alleles conferring a relative risk equal to that
      estimated for the putative 18p locus (2.58). Our results do not support a major
      role for G-olf alpha as a susceptibility locus for BPAD in a substantial portion
      of our sample. Other genes lying near G-olf alpha within the linked region on
      chromosome 18 cannot be excluded by our data. This study illustrates the use of
      the TDT in evaluating candidate genes within linked chromosome regions.

PMID- 8886170
TI  - Analysis of polyglutamine-coding repeats in the TATA-binding protein in different
      human populations and in patients with schizophrenia and bipolar affective
      disorder.
AB  - A new class of disease (including Huntington disease, Kennedy disease, and
      spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG
      trinucleotides in the coding regions of genes. In all of these diseases the CAG
      repeats are thought to be translated into polyglutamine tracts. There is
      accumulating evidence arguing for CAG trinucleotide expansions as one of the
      causative disease mutations in schizophrenia and bipolar affective disorder. We
      and others believe that the TATA-binding protein (TBP) is an important candidate
      to investigate in these diseases as it contains a highly polymorphic stretch of
      glutamine codons, which are close to the threshold length where the polyglutamine
      tracts start to be associated with disease. Thus, we examined the lengths of this
      polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub
      Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43
      bipolar affective disorder patients and 65 schizophrenic patients. The range of
      polyglutamine tractlengths that we found in humans was from 26-42 codons. No
      patients with bipolar affective disorder and schizophrenia had abnormal
      expansions at this locus.

PMID- 8886171
TI  - Nonfamiliality of the sex ratio in autism.

PMID- 8886172
TI  - Hypokalemia, high erythrocyte Na+ and low erythrocyte Na,K-ATPase in relatives of
      patients dying from sudden unexplained death syndrome in north-east Thailand and
      in survivors from near-fatal attacks.
AB  - The sudden unexplained death syndrome (SUDS) is a sudden death of unknown cause
      in healthy South-East Asians. In Thailand, it is common in the North-East region.
      We previously reported high incidences of low erythrocyte sodium and potassium
      activated adenosine triphosphatase (Na,K-ATPase) activity and of high erythrocyte
      sodium in North-East Thais and speculated that this metabolic defect might be
      associated with the high incidence of SUDS in that region. In this communication,
      we studied plasma sodium and potassium, erythrocyte sodium and potassium,
      activities of erythrocyte Na,K-ATPase, ouabain-insensitive ATPase and total
      ATPase in healthy Thai blood donors from Central Thailand (group 1), healthy
      North-East city dwellers (group 2), relatives of SUDS victims (group 3) and
      survivors from SUDS-like attacks (group 4). Compared with groups 1 and 2, group 3
      and 4 subjects had significantly lower plasma potassium (p < 0.0001), higher
      erythrocyte sodium (p < 0.0001), lower activities of erythrocyte Na,K-ATPase (p <
      0.0001) and of erythrocyte total ATPase (p < 0.0001). In addition, group 4
      subjects had lower plasma potassium, higher erythrocyte sodium and lower activity
      of total ATPase than those of group 3. The findings suggest that the pathogenesis
      of SUDS could be related to hypokalemia and a membrane sodium/potassium pump
      defect.

PMID- 8886173
TI  - Seasonal variation in the incidence of end-stage renal disease.
AB  - The effect of ambient temperature (AMT) on the incidence of end-stage renal
      disease (ESRD) was examined in Okinawa, Japan, where there is a distinct seasonal
      variation in monthly AMT but constant intradiurnal temperature change throughout
      a year. Arbitral continuous and cyclic functions were examined using Fourier
      analysis and calculation of the cross-correlation coefficient. The calendar month
      of the start of chronic dialysis was regarded as the time of onset of ESRD. A
      total of 1,982 patients, 824 females and 1,158 males, was registered with ESRD
      between 1971 and 1990. The normalized monthly number of new ESRD patients,
      divided by days of each month, was smallest in August, n = 4.06, and largest in
      January, n = 6.45, and this pattern was well reproduced by the Fourier
      synthesized value. The cross-correlation coefficient showed that monthly mean AMT
      and the normalized number of ESRD patients correlated best with 6 months lag
      time. Taken together, our results showed that there was strong correlation
      between the normalized number of ESRD patients and AMT. Uremic symptoms leading
      to initiate dialysis, such as congestive heart failure, may be aggravated in
      lower AMT. We speculated a role of an inverse relation between AMT and the
      sympathetic nerve function. The public health implications of these findings
      warrant their further investigation.

PMID- 8886174
TI  - Serum bicarbonate is an independent determinant of protein catabolic rate in
      chronic hemodialysis.
AB  - Serum bicarbonate is an independent determinant of protein catabolic rate in
      chronic hemodialysis. Recent biochemical studies suggest that metabolic acidosis
      induces an increase in protein catabolic rate. Therefore, we retrospectively
      examined the relationship between serum total CO2, normalized protein catabolic
      rate (NPCR), midweek BUN, KT/V, and serum albumin in 70 chronic hemodialysis
      patients over a period of 4-6 months (total of 270 determinations). Multiple
      regression analysis indicated an independent and inverse association of tCO2 with
      NPCR (p < 0.0001). Subsequent analysis of the data indicated a nonlinear
      relationship between serum CO2 and NPCR. Indeed, the slope of the regression
      abruptly increased from -0.015 +/- 0.005 to -0.108 +/- 0.032 when analyzed for
      serum CO2 < or = 15 mEq/l. We conclude that metabolic acidosis may modulate
      protein kinetics in patients receiving maintenance hemodialysis. Moreover, this
      relationship appears to be exaggerated at moderate to severe reductions in tCO2.
      Thus, this analysis suggests that decreases in tCO2 have a detrimental effect on
      protein catabolism in stable patients maintained on chronic hemodialysis.

PMID- 8886175
TI  - Hypocalcemia, morbidity, and mortality in end-stage renal disease.
AB  - BACKGROUND: Hypocalcemia and hyperphosphatemia with secondary hyper
      parathyroidism are characteristic of end-stage renal disease (ESRD). Although
      calcium levels critically affect almost all cellular processes, the impact of
      chronic hypocalcemia and other abnormalities of calcium-phosphate homeostasis on
      the prognosis of ESRD patients is unknown. METHODS: An inception cohort of 433
      patients starting ESRD therapy was followed prospectively for an average of 41
      months. Serum calcium and other parameters were measured monthly. The mean
      calcium levels were 9.4 +/- 0.7 mg/dl. 23% of the patients had mean calcium
      levels < 8.8 mg/dl. After adjusting for baseline age, diabetes mellitus, ischemic
      heart disease, smoking and cholesterol levels, as well as serial albumin,
      hemoglobin, mean arterial blood pressure, phosphate and alkaline phosphatase
      levels, chronic hypocalcemia was strongly associated with mortality (RR 2.10, p =
      0.006 for a mean calcium level < 8.8 mg/dl). The association with mortality was
      similar in hemodialysis (RR 2.10, p = 0.006) and peritoneal dialysis patients
      (2.67, p = 0.034). Using similar covariate adjustment, chronic hypocalcemia was
      associated with de novo ischemic heart disease (RR 5.23, p < 0.001), recurrent
      ischemic heart disease (RR 2.46, p = 0.006), de novo cardiac failure (RR 2.64, p
      < 0.001), and recurrent cardiac failure (RR 3.30, p < 0.001). Hypocalcemia
      retained its independent impact on morbidity and mortality when analyzed as a
      time-dependent covariate. CONCLUSIONS: Chronic hypocalcemia, a very common,
      reversible feature of chronic uremia, is independently associated with morbidity
      and mortality in ESRD patients.

PMID- 8886176
TI  - Neutral-lipid transfers and cholesteryl ester transfer protein in hemodialyzed
      patients.
AB  - Abnormalities in cholesteryl ester transfers may play a role in the development
      of atherosclerosis observed in patients with end-stage renal failure treated by
      chronic hemodialysis. Net neutral-lipid transfers and cholesteryl ester transfer
      protein activity and mass were investigated in 20 hemodialyzed patients,
      arbitrarily divided into two groups based on fasting triglyceride levels, and
      compared to triglyceride-matched control groups. In the hypertriglyceridemic
      subjects (plasma triglyceride values > 150 mg/dl), high-density lipoprotein
      cholesterol was decreased, and the net cholesteryl ester transfer rates were
      significantly higher than the rates in normolipidemic subjects. The comparison of
      subjects matched for plasma triglyceride and cholesterol levels showed no
      significant difference in cholesteryl ester or triglyceride transfer rates
      between patients and controls. Our results suggest that normal or elevated net
      neutral-lipid transfers are not related to the renal status of the subjects, but
      rather to their plasma triglyceride levels.

PMID- 8886177
TI  - Alpha-V/beta-3 and alpha-V/beta-5 integrin distribution in neoplastic kidney.
AB  - Integrins are transmembrane glycoproteins that mediate cell-cell and cell-matrix
      interactions. Altered integrin expression may contribute to tumor progression,
      invasiveness and metastases. The alpha-V/beta-3 (alpha v beta 3; osteopontin/
      vitronectin receptor) has recently been implicated in neovascularization and
      tumor-induced angiogenesis. alpha v-Subunit also associates with beta 5 to form
      an alpha v beta 5-complex, another vitronectin receptor. We studied tissue
      distribution of alpha v beta 3-and alpha v beta 5-integrins, as well as alpha 1-
      and beta 1-subunits in nephrectomy samples from 7 subjects with localized renal
      cell carcinoma. Grossly and histologically uninvolved regions ('normal') from the
      same nephrectomy specimens were used for comparison. Integrin expression was
      studied with specific monoclonal antibodies and the immunoperoxidase technique.
      alpha v beta 3 was expressed in the glomerular epithelial cells, Bowman's
      capsule, vascular endothelium, and weakly in tubular epithelial cells. alpha v
      beta 5 had a similar distribution except for minimal expression on vascular
      endothelium. alpha 1-Expression was observed in mesangium and but weakly in
      Bowman's capsule. beta 1-Expression was seen in glomerular epithelial cells,
      Bowman's capsule, vascular epithelium and tubular epithelial cells. Unlike in
      'normals', neoplastic expression was more heterogeneous alpha v beta 3 was
      expressed in tumor cells in 4/7 cases, vascular endothelium in 6/6, and in stroma
      in 4/7. alpha v beta 5 was weakly expressed in tumor cells in 4/5, vascular
      endothelium in 5/5, and stroma in 4/5 cases. alpha 1-Expression was seen in tumor
      cells in 3/7, vascular endothelium in 4/7 and in stroma in 7/7 cases. beta 1
      Expression was seen in tumor cells in 7/7 cases, vascular endothelium in 7/7, and
      in stroma in 4/7 cases. This study delineates the pattern of expression of the
      alpha v beta 3-and alpha v beta 5-integrins in 'normal' and neoplastic human
      kidney. Variations in alpha v beta 3-and alpha v beta 5-integrin expression may
      play a role in normal and neoplastic processes of the kidney.

PMID- 8886178
TI  - Plasma phospholipids and platelet function in uremic patients.
AB  - An increased activity of phospholipase A2 has been observed in the plasma of
      patients with uremia. This enzyme converts phosphatidylcholine to
      lysophosphatidylcholine (LPC), an inhibitor of platelet aggregation. We measured
      the levels of plasma phospholipids including LPC, and platelet aggregation in 7
      patients with uremia. Platelet response to agonists was defective, mainly with
      collagen (p < 0.001). The patients' levels of LPC in plasma were similar to those
      of controls (109.7 +/- 41.6 vs. 80.4 +/- 16.8 nmol/ml) and did not correlate with
      the platelet response to adenosine diphosphate (r = -0.51). The amount of
      phosphatidylcholine was increased with respect to normal plasma (1,041.0 +/-
      201.8 vs. 760.8 +/- 142.7 nmol/ml, p < 0.01), while the levels of other
      phospholipids were normal. These results do not suggest a participation of plasma
      LPC in the genesis of the platelet defect observed in patients with uremia.

PMID- 8886179
TI  - Isolated hematuria in adults: IgA nephropathy is a predominant cause of hematuria
      compared with thin glomerular basement membrane nephropathy.
AB  - We examined kidney biopsy specimens obtained from 40 adult patients with isolated
      hematuria to determine the renal pathology and the incidence of thin glomerular
      basement membrane nephropathy (TGBMN). Light microscopy showed minor glomerular
      abnormalities in 26 patients (65%), focal and segmental lesions in 3 patients
      (8%), and mild diffuse proliferative glomerulonephritis in 11 patients (28%).
      Immunofluorescence microscopy showed IgA nephropathy (IgA-N) in 16 patients
      (40%), in whom no progressive lesions were identified. We measured the glomerular
      basement membrane (GBM) thickness using electron microscopy, and TGBMN was
      identified in 4 patients (10%). Our results suggest that IgA is a major
      pathological finding in adult patients with isolated hematuria. GBM thinning does
      not appear to be a major cause of glomerular hematuria.

PMID- 8886180
TI  - A 19-year-old female with fever, acroparesthesia, and progressive deterioration
      of renal function.

PMID- 8886181
TI  - Interrelationship between renal mass and renotropin activity in consecutive
      generations of uninephrectomized mice.
AB  - In offspring of uninephrectomized mouse mothers at ages 3, 5 and 7 weeks (n = 8
      in each group) fresh and dry kidney weights, protein content, mean number of
      glomeruli per microscopic field (GN), mean cumulative fractional glomerular area
      per microscopic field (GA) and mean number of nuclei per glomerulus (GC) were all
      significantly increased compared to age-matched control offspring of sham
      nephrectomized mothers. Sera from mice at ages 3 and 5 weeks, offspring of
      uninephrectomized mothers, stimulated mesangial cell proliferation in culture.
      Surprisingly, fresh and dry renal weight, GN, GA and GC were all significantly
      increased in offspring of sham nephrectomized mothers, daughters of
      uninephrectomized grandmothers. We speculate that elevated maternal renotropin
      transferred via the placenta introduces a modification in the embryonal
      interrelationship between renal mass and endogenous renotropin. This modification
      results in exaggerated embryonal serum renotropic activity extending to puberty.
      Whether the humoral agent responsible for enhanced mesangial cell proliferation
      in vitro is identical to renotropin remains to be elucidated.

PMID- 8886182
TI  - Effects of parathyroid hormone on hepatocyte pHi and Na(+)-H+ exchanger activity.
AB  - Parathyroid hormone (PTH) induces a rise in cytosolic calcium--[Ca2+]i--in many
      cells. A rise in [Ca2+]i activates the Na(+)-H+ antiport, but PTH inhibits the
      Na(+)-H+ exchanger in kidney cells. Since PTH induces a rise in [Ca2+]i of
      hepatocytes, we examined the effect of PTH on their Na(+)-H+ antiport and
      intracellular pH(pHi). PTH caused an initial activation of Na(+)-H+ exchanger,
      and this stimulation is amiloride sensitive. The activation of the Na(+)-H+
      exchanger was followed by progressive inhibition. This inhibitory effect was dose
      dependent and occurred over a wide range of external sodium concentrations. PTH
      also caused a progressive rise in hepatocyte pHi which became apparent after the
      initial activation of the Na(+)-H+ antiport. This alkalinization of hepatocytes
      occurred when the cells were placed in sodium or potassium media. These actions
      of PTH were mimicked by dibutyryl cyclic AMP and 12-o-tetradecanoylphorbol-13
      acetate(TPA) and were abolished by H-89 (an inhibitor of protein kinase A),
      staurosporine (an inhibitor of protein kinase C), and the calcium channel
      blockers verapamil or nifedipine. The data are consistent with the formulation
      that PTH, through the activation of the cAMP-protein kinase A pathway, protein
      kinase C, and calcium channels inhibitable by verapamil or nifedipine, induces a
      rise in [Ca2+]i of hepatocytes. The latter event causes an initial activation of
      Na(+)-H+ antiport which is followed by a rise in pHi. Also, PTH may facilitate a
      Ca2+/2H+ exchange across the hepatocyte membrane and causes an initial and
      persistent rise in pHi, since the rise in pHi occurred under conditions where
      Na(+)-H+ antiport is inactive (potassium media). In addition, PTH either directly
      or through activation of second messenger(s) leads to an increased ammonia
      content of hepatocytes which could maintain a high pHi. Consequently, the Na(+)
      H+ antiport is inhibited in an effort to restore the pHi back to normal.

PMID- 8886183
TI  - Polyarteritis nodosa and antiglomerular basement membrane disease without
      antineutrophil cytoplasm antibodies.
AB  - Antiglomerular basement membrane (GBM) antibodies have been described previously
      in patients with microscopic polyarteritis but not in patients with polyarteritis
      nodosa alone. Where anti-GBM antibodies occur in microscopic polyarteritis,
      antineutrophil cytoplasm antibodies (ANCA) are usually present. We describe here
      a patient with polyarteritis nodosa and anti-GBM antibodies in whom ANCA could
      not be demonstrated. A 72-year-old woman presented with abdominal pain, diarrhoea
      and acute renal failure. A renal biopsy showed crescentic glomerulonephritis and
      linear immunofluorescence of the GBM consistent with anti-GBM disease. In
      addition, there was evidence of large-and medium-sized vessel vasculitis on
      abdominal angiography, performed because of persisting abdominal pain. There was
      no small vessel vasculitis on histological examination of the renal biopsy and
      ANCA could not be demonstrated by indirect immunofluorescence or ELISA.

PMID- 8886184
TI  - Disparate prognosis of thrombotic microangiopathy in HIV-infected patients with
      and without AIDS.
AB  - Thrombotic microangiopathy (TMA) is more common in HIV-infected individuals than
      in the normal population. In idiopathic TMA, plasmapheresis with or without
      prednisone decreases the mortality rate from almost 100 to 10%. Patients with HIV
      associated TMA, who do not have AIDS, have a similar favorable outcome when
      treated with plasmapheresis. However, all 12 patients previously reported with
      AIDS-associated TMA have died. We report another patient with AIDS-associated
      TMA, who had a fulminant hospital course and died despite plasmapheresis. None of
      the reported AIDS-associated TMA patients had evidence of opportunistic
      infections, sepsis or disseminated malignancies at the time of their death. Since
      many infections and malignancies can be associated with TMA, it is possible that
      TMA can be an association of the terminal illness rather than an independent
      cause of death in AIDS patients. To examine this possibility, we reviewed the
      charts of all the patients who were hospitalized and died of AIDS at our medical
      centers from 1987 to 1994. Of the 214 patients reviewed, 15 patients (7%) had
      evidence of TMA at the time of their death. Seven of the 15 patients (47%) had no
      direct cause of death other than TMA. The remaining 8 patients had evidence of
      sepsis and other overwhelming infections. In conclusion, TMA is common in AIDS
      patients. While HIV-associated TMA has a good prognosis similar to that of
      idiopathic TMA, AIDS-associated TMA has a grave prognosis. The etiology of the
      higher mortality in AIDS-associated TMA as compared to HIV-associated TMA remains
      unclear.

PMID- 8886185
TI  - Ketanserin and erythropoiesis in hemodialysis patients with polycystic kidneys.

PMID- 8886186
TI  - Impact of human recombinant erythropoietin on plasminogen activator inhibitor,
      and protein C and S activity.

PMID- 8886187
TI  - Roles for school-based occupational therapists: past, present, future.

PMID- 8886188
TI  - Providing effective occupational therapy services: data-based decision making in
      school-based practice.
AB  - Educational practice is moving away from an "eligibility-oriented" student
      problem approach toward a problem-solving approach that connects evaluation and
      interventions. This approach involves the identification of variables used to
      frame interventions, and, ultimately, it permits evaluation of intervention
      effectiveness. This article describes a problem-solving model developed and used
      within the Heartland Area Education Agency. This model relies on collecting
      baseline data and ongoing data, producing a basis not only for decision making,
      but also for evaluating the chosen intervention. This systematic and
      collaborative approach is used by the educational team to identify concerns about
      students' academic and nonacademic performance, to plan interventions, and to
      establish measurable outcomes.

PMID- 8886189
TI  - Collaborative consultation: the efficacy of remedial and compensatory
      interventions in school contexts.
AB  - OBJECTIVE: This study examined the intervention success of weekly collaborative
      consultation between therapists and teachers. METHOD: Ten therapist-teacher pairs
      consulted for 60 min weekly throughout the school year about students identified
      as having sensory integration dysfunction with learning problems. Each week, the
      pairs identified a specific functional classroom goal then designed either a
      remedial or compensatory intervention and set criteria for intervention success.
      At each successive weekly meeting, the pairs determined whether the goal was met.
      Intervention success was analyzed across 10 students (for a total of 213 goals).
      RESULTS: There was a positive effect for overall intervention success. Although
      remedial and compensatory interventions were equally successful across student
      performance areas, therapist-teacher pairs demonstrated a preference for
      compensatory and academic goals. CONCLUSION: The overall positive effect for
      intervention success suggests that when occupational therapists and teachers
      collaborate on behalf of students, they can facilitate student success in a
      variety of performance areas. Therapist-teacher preference for compensatory and
      academic goals indicates that therapist-teacher collaboration can be useful for
      occupational therapists to link interventions to academic goals in school
      contexts.

PMID- 8886190
TI  - Occupational therapy in full-inclusion classrooms: a case study from the Moorpark
      model.
AB  - This article provides a historic review of the movement toward integrated
      classroom placements as well as the characteristics of full-inclusion classrooms
      relevant to occupational therapy school-based practice. A full-inclusion model
      adopted by the Moorpark Unified School District is described. This model
      incorporates occupational therapy as a vital and integral component of the
      school's inclusive education efforts.

PMID- 8886191
TI  - Supervision and consultation services for pediatric occupational therapists.
AB  - OBJECTIVE: Occupational therapists with advanced experience or expertise provide
      supervision and consultation services in a variety of settings. This pilot study
      examined the use of such supervision and consultation services by pediatric
      occupational therapists. METHOD: Special education administrators and pediatric
      occupational therapists from Massachusetts, a state often regarded as a leader in
      special education, responded to surveys designed especially for this study. These
      surveys asked about current supervision and consultation use, satisfaction with
      present services, and the need for additional resources in this area. Opinions
      regarding practice areas that would best be addressed by supervision and
      consultation were also obtained. RESULTS: Both administrator and therapist
      respondents agreed that expert occupational therapy supervision and consultation
      are needed. Identified areas of interest were classroom supervision and
      consultation strategies, service delivery decisions, and evaluation methods.
      CONCLUSION: Pediatric occupational therapists need expert supervision and
      consultation from occupational therapists with advanced experience or expertise
      in addition to traditional management, education, and training methods.

PMID- 8886192
TI  - Factors that relate to good and poor handwriting.
AB  - OBJECTIVE: This study investigated the relationships between specific performance
      components, eye-hand coordination, visuomotor integration, in-hand manipulation,
      and handwriting skill. METHOD: A sample of 48 typical first grade students were
      identified as good and poor handwriters by their teachers. Each child completed
      the Motor Accuracy Test; the Developmental Test of Visual-Motor Integration
      (VMI); two tests of in-hand manipulation, including a rotation and a translation
      task; and the Minnesota Handwriting Test (MHT). RESULTS: All test scores for the
      subjects with good handwriting were significantly higher than those of the
      subjects with poor handwriting. Each performance component test was significantly
      correlated to MHT scores. Translation, VMI, and rotation scores were significant
      predictors of MHT scores, accounting for almost 73% of variance. A discriminant
      analysis using the performance components correctly classified 98% of the
      students as good or poor handwriters. CONCLUSION: In-hand manipulation has
      significant association to handwriting skill.

PMID- 8886193
TI  - A compensatory counting system: academic skill training.

PMID- 8886194
TI  - A pilot study of needs assessment for school-based occupational therapy.

PMID- 8886195
TI  - What is the problem with third-party prescription in school-based practice?

PMID- 8886196
TI  - Current status of IDEA reauthorization.

PMID- 8886197
TI  - Cigarette smoking and its orthopedic consequences.
AB  - Cigarette smoking and its ramifications are coming under increasing scrutiny in
      the field of orthopedic surgery. Smoking has been implicated in impeding bone
      metabolism and fracture repair, and increasing the rate of postoperative
      infection and the incidence of nonunion. This article reviews the current body of
      knowledge on these topics, as well as the potential adverse effects of smoking on
      wound healing and microsurgical procedures. An in-depth discussion on the
      pathophysiologic mechanisms of nicotine is also included.

PMID- 8886198
TI  - The Thomas splint. Questionable boast of an indispensable tool.
AB  - The Thomas splint has been used since the late 1800s. During World War I,
      physicians began using it for the acute management of femoral fractures and
      attributed its use to reduced mortality associated with these injuries. However,
      articles differ as to the actual percentage of mortality reduction. Even though
      these discrepancies exist, the Thomas splint has been useful and is still used
      today, especially for patient transport while awaiting definitive management.

PMID- 8886199
TI  - In-hospital charges associated with the treatment of adult femoral neck
      fractures.
AB  - A retrospective analysis of 41 adult patients treated for a femoral neck fracture
      was performed to determine the variables that best predict total hospital
      charges. The patients were treated for an isolated femoral neck fracture at our
      hospital from January 1993 through December 1994. There were 13 men and 28 women.
      The average age at the time of injury was 63 years. The average length of stay
      was 12.1 days, and the average total hospital charges per patient were $16,072.
      No physician fees were included in our analysis. Detailed multivariate regression
      analysis of 10 variables was performed for each patient. Stepwise linear
      regression analysis, which controlled for all variable (such as age at injury,
      number of medical illnesses, gender, and others), revealed that the strongest
      predictors of total hospital charges were the number of medical illnesses (P <
      0.0001), age at injury (P = 0.023), length of stay (P < 0.0001), and number of
      complications (P = 0.0007).

PMID- 8886200
TI  - Acoustic assessment of fracture healing. Capabilities and limitations of "a lost
      art".
AB  - The ability of bone to conduct sound was applied clinically over 50 years ago to
      identify the presence of fresh fractures, although the technique has become a
      relatively "a lost art" as more sophisticated X-ray and other imaging techniques
      have been developed. The objective of this report is to challenge clinical
      orthopaedic surgeons unfamiliar with the technique to explore this simple beside
      method in the clinical management of fractures. A portable computer-based
      vibrational analysis device was employed and experiments conducted to objectively
      evaluate the capabilities of auscultatory percussion techniques. Auscultatory
      percussion can, with certain limitations, detect the presence of fractures,
      assess qualitatively the progress of healing, detect delayed or nonunions, and
      indicate when sufficiently firm continuity has occurred to permit early
      mobilization or loadbearing. Vibrational assessment is, however, subject to
      systematic and random errors, and thus cannot always discriminate between the
      stages of healing in a fractured bone; in addition, various artifacts can lead to
      significant uncertainty in the diagnosis. Nevertheless, auscultatory percussion
      is a useful tool in clinical fracture management, and particularly where
      roentgenographic facilities are inadequate or not available. Computerized
      vibrational analysis can be used in place of classical percussion/stethoscope
      methods by those with poor tonal capabilities,or when more objective record
      keeping is desired.

PMID- 8886201
TI  - The triceps-splitting approach for repair of distal humeral malunion in children.
      A report of a technique.
AB  - Repair of cubitus varus in a child requires a distal humeral osteotomy. The
      triceps-splitting surgical approach was used for repair of distal humeral
      malunion in 10 children. Six patients had repair of cubitus varus, 3 had fixation
      of a fresh fracture, and 1 had repair of a nonunion. No problems with healing
      were noted. Triceps weakness and elbow stiffness did not occur. The triceps
      splitting approach is particularly well suited for repair of cubitus varus in
      children because, compared with the lateral approach, it is cosmetically
      favorable, avoids ulnar and cutaneous nerves, does not damage extensor function,
      provides excellent visualization of the osteotomy site, and does not result in
      joint stiffness.

PMID- 8886202
TI  - Anatomy of the posterolateral disc region.
AB  - Eighteen cadaveric dissections were performed to determine the location of the
      segmental vessels and the cephalad nerve root in relation to the posterolateral
      lumbar disc. The most lateral point of each lumbar disc was determined, and
      measurements were made form this reference point. Segmental vessels were found to
      be a mean of 10 to 13 mm from the junction of the vertebral body and the disc.
      The exception to this was the vessel superior to L5-S1, which was a mean of 7 mm
      from the disc margin. The cephalad nerve roots were consistently found to be
      adjacent to the disc, and were an average of 9 to 22 mm posterior to the lateral
      reference point.

PMID- 8886203
TI  - Recovery of unused operating room supplies for overseas orthopedic surgery.
AB  - Recovery of surplus operating room (OR) materials may contribute needed supplies
      to volunteer overseas surgical efforts. However, recovery often generates
      supplies that are highly heterogeneous in nature. In order to evaluate the nature
      and quantity of supplies useful to orthopedic surgical missions, the present
      investigation evaluated the material generated from 381 consecutive orthopedic
      cases performed during three 3-month assessment periods over 3 years. The amount
      of recovered material varied markedly within and among procedure types as well as
      surgeons. Nevertheless, the long-term, OR-wide recovery program at Yale-New Haven
      Hospital has provided a highly reliable source of usable materials over the 4
      year life of the program.

PMID- 8886204
TI  - Progressive scapulothoracic subluxation after fracture of the clavicle.
AB  - Fracture of the clavicle is a common injury that usually heals without
      consequence. Instability of the scapulothoracic articulation does not usually
      occur. In this case, the scapulothoracic subluxation was not obvious at the time
      of injury, but progressively worsened over the following 2 weeks. Open reduction
      and internal fixation of the clavicle fracture restored stability to the shoulder
      girdle. The patient went on to regain full function of her injured extremity.

PMID- 8886205
TI  - Spontaneous resolution of soft-tissue interposition after closed reduction of hip
      endoprosthesis dislocation.
AB  - Over a 5-year period at a single institution, 164 endoprostheses were used for
      the treatment of displaced femoral neck fractures. Soft-tissue restraint
      preservation and repair (hip capsule and labrum) is recommended to enhance
      stability after endoprosthesis placement. When dislocation does occur, however,
      this soft tissue may become interposed after closed reduction. This occurred in 2
      of the dislocations reported here. In these 2 dislocations, despite the widened
      joint space, the range of motion was stable. Neither of these cases had a
      subsequent dislocation, and after 1 month, both had spontaneously narrowed their
      joint space back to the immediate postoperative state.

PMID- 8886206
TI  - Traumatic hip dislocation during childhood. A case report and review of the
      literature.
AB  - Traumatic hip dislocations rarely occur during childhood. Males sustain pediatric
      hip dislocations four times more often than do females. Posterior hip
      dislocations comprise 87% of all pediatric hip dislocations. A soft, pliable
      acetabulum and ligamentous laxity predispose the immature hip joint to a
      dislocation secondary to minimal trauma. Potential associated injuries include
      fractures and neurovascular injury, whereas avascular necrosis (AVN) and
      degenerative joint disease are potential sequelae. Optimal treatment should be
      prompt reduction of the hip in order to minimize the risk of AVN of the femoral
      head.

PMID- 8886207
TI  - "Two stitch" carpal tunnel surgery. A mini-incision technique.
AB  - A new mini-incision technique with the advantage of visualizing the median nerve
      and carpal ligament and preserving the overlying soft (pillar) tissue is
      presented. With this "two stitch" technique, surgeons can be assured that the
      median nerve and its sensory branches are protected and the volar ligament is
      completely released.

PMID- 8886208
TI  - A 42-year-old woman with low back pain.
AB  - The following case is presented to illustrate the roentgenographic and clinical
      findings of a condition of interest to orthopedic surgeons. The initial history,
      physical findings, and roentgenographic examinations are noted on this page. The
      clinical and roentgenographic diagnoses are presented on the following pages.

PMID- 8886209
TI  - Bilateral knee replacement.

PMID- 8886210
TI  - Simultaneous bilateral total knee replacement vs. unilateral replacement.

PMID- 8886211
TI  - The appropriate use of NSAIDs in arthritic conditions.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important component of
      therapy for many of the arthritides. They are of value in the treatment of
      rheumatoid arthritis (RA) and other arthritides with inflammatory characteristics
      and are frequently used to treat osteoarthritis (OA) when simple analgesics fail
      to provide relief. There is a great deal of interpatient variability with respect
      to response to NSAIDs; however, it is currently difficult to predict which
      patient will respond best to which drug. As a result, NSAID selection is based
      both on the medical history of the individual patient and the adverse-events
      profiles of the available agents. In general, patients on NSAIDs should be
      monitored closely for adverse events, particularly those patients with a history
      of, or risk factors for, gastrointestinal, renal, or hepatic disease. Use of the
      cytoprotective agent misoprostol is indicated in patients at high risk for
      gastrointestinal irritation. Although H2-antagonists in high dosages may be
      effective in the prophylaxis of gastropathy, there is some concern that use of
      these agents at usual dose levels may create a potential for adverse events by
      masking the pain associated with ongoing gastric erosive changes.

PMID- 8886212
TI  - IPDAS: a novel technology brings new benefits when applied to naproxen sodium.
AB  - The Intestinal Protective Drug Absorption System (IPDAS) is a new oral drug
      delivery approach that is applicable to gastrointestinal (GI) irritant drugs,
      including the nonsteroidal anti-inflammatory drug (NSAID) class. Although
      naproxen, as the free acid or the sodium salt, has pharmacokinetic
      characteristics that are consistent with once-daily dosing, the GI irritant and
      ulcerogenic potential associated with a large bolus dose of naproxen precludes
      safe use of an immediate-release form. In addition, the desired pharmacodynamic
      activity of a once-daily dosage form of naproxen requires rapidly available
      naproxen for a prompt onset of analgesic activity, as well as a prolonged phase
      of absorption to provide 24-hour analgesic/anti-inflammatory activity. Naprelan
      (naproxen sodium; Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania)
      controlled-release tablets are a unique dosage form designed to achieve the
      desired features of such a once-daily presentation. Through a series of in vivo
      studies, the pharmaceutical design features of the product have been confirmed in
      humans using a combination of imaging and pharmacokinetic characterization. In
      addition, the potential for limiting any undesirable GI adverse events has been
      supported by evaluation of the GI toxicity of Naprelan in specialized animal
      toxicity studies. Naprelan exhibited in vivo performance characteristics that
      support the hypothesis that, as a once-daily dosage form, it may demonstrate
      safety and efficacy advantages in clinical evaluation.

PMID- 8886213
TI  - A comparison of Naprelan and Naprosyn in the treatment of osteoarthritis of the
      knee.
AB  - This double-blind, double-dummy, placebo-controlled, randomized study compared
      the safety and efficacy of Naprelan (Wyeth-Ayerst Laboratories, Philadelphia,
      Pennsylvania), a once-daily, controlled-release formulation of naproxen sodium
      with that of Naprosyn (Syntex Laboratories, Inc., Palo Alto, California), a
      conventional naproxen formulation. A total of 347 patients with osteoarthritis
      (OA) of the knee were assigned to receive Naprelan 1,000 mg once daily, Naprosyn
      500 mg BID, or placebo for 12 weeks. Two hundred twenty-eight patients who
      completed the study then entered an open-label extension in which they received
      Naprelan 1,000 mg daily for as many as 9 additional months. In the double-blind
      phase, Naprelan and Naprosyn demonstrated comparable efficacy with no significant
      differences in mean efficacy scores. After 12 weeks, three primary variables
      significantly favored Naprelan and Naprosyn over placebo, while a fourth
      approached significance. Statistical analysis confirmed that Naprelan and
      Naprosyn were equally effective. Significantly more Naprosyn--than placebo
      treated patients had at least one drug-related adverse event (AE) and at least
      one drug-related gastrointestinal (GI) system AE, but there were no significant
      differences between Naprelan and placebo. During the open-label phase, patients
      initially treated with Naprelan or Naprosyn maintained the improvement achieved
      in the double-blind phase, while those initially treated with placebo showed
      significantly greater improvement after the first month of Naprelan treatment
      than the other two groups. As assessed by one of two primary efficacy measures,
      the greater improvement in those initially treated with placebo was maintained
      until the end of the study. The AE profile for patients treated with Naprelan for
      up to 1 year was not significantly different than that for the double-blind
      phase. The results of this study have confirmed the efficacy of Naprelan 1,000 mg
      once daily in the treatment of OA as superior to placebo and equivalent to
      Naprosyn 500 mg BID.

PMID- 8886214
TI  - Clinical efficacy and safety of Naprelan versus Naprosyn in the treatment of
      rheumatoid arthritis.
AB  - A double-blind, randomized study compared the efficacy and safety of a controlled
      release naproxen sodium formulation (Naprelan, Wyeth-Ayerst Laboratories,
      Philadelphia, Pennsylvania) 1,000 mg once daily; a conventional naproxen
      formulation (Naprosyn, Syntex Laboratories, Inc., Palo Alto, California) 500 mg
      BID; and placebo given for 12 weeks to 348 patients with rheumatoid arthritis
      (RA). This was followed by an open-label study to evaluate the safety of naprelan
      1,000 mg once daily for an additional 9 months. In the double-blind phase of this
      study, the safety and efficacy of Naprelan 1,000 mg once daily were compared with
      those of Naprosyn 500 mg twice daily and placebo in 348 patients with RA. At the
      end of 12 weeks of treatment, Naprelan and Naprosyn were numerically superior to
      placebo in 3 of the 4 primary efficacy variables--physician's global assessment,
      patient's global assessment, and number of painful joints. Differences between
      Naprelan and placebo reached statistical significance for the patient's global
      assessment at Week 12 (Visit 7). Significantly more Naprosyn- than placebo
      treated patients had at least 1 severe digestive system adverse event (AE); 1
      drug-related AE; or 1 drug-related, digestive-system AE. There was no
      statistically significant difference in the number of AEs experienced by Naprelan
      treated patients compared with those who received placebo. A total of 240
      patients enrolled in the Naprelan open-label phase. As would be expected,
      patients initially treated with placebo showed significant improvement after
      starting Naprelan. Those initially receiving Naprelan or Naprosyn also maintained
      their improvement. The AE profile with Naprelan was similar to that reported in
      the double-blind phase. It was concluded that Naprelan 1,000 mg once daily was as
      effective as Naprosyn 500 mg BID in the treatment of RA and was particularly
      effective in relieving pain later in the day. The controlled-release formulation
      may also offer safety benefits.

PMID- 8886215
TI  - Two comparative endoscopic evaluations of Naprelan.
AB  - This paper describes the results of two endoscopic studies of Naprelan (Wyeth
      Ayerst Laboratories, Philadelphia, Pennsylvania), a controlled-release
      formulation of naproxen sodium. In one study, 19 healthy male subjects received
      either 2 controlled release Naprelan 500-mg tablets once daily or 1 Naprosyn
      (naproxen; Syntex Laboratories, Inc., Palo Alto, California) 500-mg tablet BID.
      At baseline, all subjects had gastroduodenal endoscopy scores of 0 on both the
      Lanza and Euler scales. Although the trend favored Naprelan, differences in Lanza
      and Euler scale elevations were not statistically significant. Eight of 10
      subjects in the Naprelan group and 7 of 9 subjects in the Naprosyn group reported
      a total of 27 adverse events (AEs). In the second study, healthy subjects
      received Naprelan 1,000 mg once daily, Naprosyn 500 mg BID, and film-coated
      aspirin 650 mg QID. In the stomach, there was a significant difference in favor
      of Naprelan over aspirin (P = 0.0001) and in favor of Naprosyn over aspirin (P =
      0.0001). Fewer erosions were seen in the duodenum than in the stomach. In the
      duodenum, there was a significant difference in favor of Naprelan over Naprosyn
      (P = 0.0236), and in favor of Naprelan over aspirin (P = 0.0086), but the
      difference between Naprosyn and aspirin was not significant (P = 0.6643). Of the
      23 subjects who received medication, 12 reported AEs: 8 while receiving aspirin,
      3 while receiving Naprosyn, and 1 while receiving Naprelan. Differences in the
      number of erosions and ulcers seen following each of the periods of drug
      administration favored Naprelan and the Intestinal Protective Drug Absorption
      System.

PMID- 8886216
TI  - A double-blind, randomized, parallel-group study of the pharmacokinetics and
      onset of action of Naprelan in patients following oral surgery.
AB  - Naprelan (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) is a novel
      formulation of naproxen sodium designed to offer both a rapid onset and a
      sustained duration of analgesia. Its onset of action was assessed in a double
      blind, double-dummy, randomized, parallel-group study of 129 patients who had
      just undergone oral surgery to remove impacted third molars. Patients received
      Naprelan (500 mg or 1,000 mg), naproxen (500 mg), codeine (30 mg), or placebo.
      Both doses of Naprelan compared favorably with the established Naprosyn
      (formulation of naproxen; Syntex Laboratories, Inc., Palo Alto, California) with
      respect to onset of action, which occurred within 30 minutes in the majority of
      patients. The relative adverse effect profile showed that both Naprelan doses
      were as well tolerated as Naprosyn, codeine, and placebo. Pharmacokinetic and
      pharmacodynamic analysis confirmed the findings of previous Phase I studies in
      healthy subjects.

PMID- 8886217
TI  - Direct interpretation of dreams: neuropsychology.
AB  - Although the role and importance of the interpretation of dreams has been de
      emphasized in clinical discussions for the past several decades, new models of
      dream physiology suggest the central role and importance of dreams in the
      regulation of behavior. According to a body of current research, dreams
      potentiate new pathways of problem solving. A review of the neurophysiological
      literature pertinent to direct interpretation suggests dreams are sustained by
      midbrain anatomical networks with feed-back and feed-forward links to the cortex.
      The anatomical networks are termed the endogenous-intraorganismic system, the
      exogenous-transactional system, and the relational system that correspond to
      subjective, objective, and relational dreams in direct interpretation. Just as
      ordinary thought is the province of the dominant or left hemisphere, dreams are
      the province of the nondominant or right hemisphere. During REM states new
      pathways of problem solving are laid down by the nondominant hemisphere. In the
      awake state, thought and behavior about content that relates to dream material
      follow these pathways. The new neuropsychology of dreams reaffirms the central
      role of dreams in the organization of affect, emotion, intention, and general
      adaptation.

PMID- 8886218
TI  - "Fearing our mothers": an overview of the psychoanalytic theories concerning the
      vagina dentata motif F547.1.1.

PMID- 8886219
TI  - The happy home myth: the female experience.

PMID- 8886220
TI  - From the word to the scene: an expanded conceptualization for therapeutic action.

PMID- 8886221
TI  - A transfer of technique: from induced song recall to the induced recall of
      paintings.

PMID- 8886222
TI  - Creativity and the sense of self: a review essay.

PMID- 8886223
TI  - Jung's contribution to the evolving concept of self.

PMID- 8886224
TI  - The blood and guts of analysis at five years to the millennium.

PMID- 8886225
TI  - Feminism and postmodern psychoanalysis.

PMID- 8886226
TI  - Ethics and psychotherapy.

PMID- 8886227
TI  - Values in psychotherapy.
AB  - There is a tension between those who hold that psychotherapy is a scientific
      discipline and therefore "value-free," and those who believe that values are
      inherent in the nature of psychotherapy. Psychoanalysis has moved from a science
      based ideology, through the ethical concerns of Melanie Klein, to a recognition
      of the "aesthetic" dimension--the creation of suitable forms that can contain
      psychological distress. From this latter perspective, the antagonism between
      religion and psychotherapy, initiated by Freud, becomes less acute. Action-based
      ethical systems, which ignore the inner world, are critically scrutinized. The
      evidence suggesting there is a relationship between good outcome in psychotherapy
      and shared values between therapist and client is reviewed. It is posited that
      through examination of the "ethical countertransference," therapists should
      become aware of their own value systems and how they influence practice.

PMID- 8886228
TI  - Working with the family: the role of values.
AB  - In this paper, we have examined that ethical aspect of working with families
      which stresses the relevance of values. Given that values are at the heart of
      both the family's and the therapists's view of the world, we see it as crucial
      for them to be addressed in the course of assessment and treatment. A variety of
      approaches have been adopted by clinicians ranging from those who regard ethics
      as a cornerstone of therapy to more compartmentalized positions, whereby specific
      sociopolitical themes like racism, poverty, and sexism are highlighted. Whatever
      model is preferred, the essential task is to accept that values are a necessary
      feature of therapeutic work and require negotiation. Failure to do so may have
      adverse repercussions on the therapist-family relationship, even to the point of
      jeopardizing therapy. Guidelines can be articulated to forestall such unfortunate
      consequences. We have attempted to identify these in the hope of clarifying for
      therapists the necessary steps they need to take to safeguard the family's
      interests and achieve an optimal ethical (and clinical) outcome.

PMID- 8886229
TI  - The rights of the child in psychotherapy.
AB  - A brief historical perspective on the development of the concept of children's
      rights provides the background from which to delve into their rights when in
      psychotherapy. After centuries of the systematic ill-treatment of children, the
      emergence of an empathic ethos that pervaded Western society in the eighteenth
      century ushered in a new attitude of social reform. Social progress over the next
      two centuries culminated in the United Nations Convention on the Rights of the
      Child. The modern concept of the rights of the child and application of the best
      interest-of-the-child standards in child care is evident in four areas of child
      psychotherapy: informed consent; recognition of the difference between the
      child's withdrawal of consent to further therapy and resistance in therapy; the
      need to distinguish between "difficult to treat" and "unsuitable for treatment"
      cases; and empathic listening. However, mounting evidence that dysfunctional
      families cause increasing vulnerability of the child to future mental disorder
      places an obligation on the therapist to recognize the interlocking
      psychopathology and needs of both parents and children for therapy. Finally, the
      effect on child psychotherapy of "managed care" in the United States, which
      threatens to transform a best-interest-of-the-child standard to a "minimum
      interest-of-the-child" one as a socially regulated form of restrictive care,
      contravenes the child's right to optimal care. Principles relating to the well
      being of the child in psychotherapy are offered to counter this trend.

PMID- 8886230
TI  - Ethical dimensions of psychotherapy: a personal perspective.
AB  - A substantial increase in the interest devoted to ethical issues has been a
      defining feature of my 50 years in psychotherapeutic practice. Reasons include a
      shift from a paternalistic to a contractual model of the doctor-patient
      relationship, increased litigiousness, and greater emphasis on the business
      rather than professional aspects of practice. Many ethical violations stem from
      misuse of therapist power in the psychotherapeutic relationship. One of the most
      egregious of these is overt sexual acting out between therapist and patient, a
      dereliction now viewed much more sternly, largely because of the rise of the
      women's movement. Therapist power can also be misused for purposes of
      psychopathological gratification, such as to dominate patients or impose values,
      and by emphasizing financial rewards over patient needs. A sea change I have
      observed has been the gradual replacement of a two-party by a three-party system
      of payment for psychotherapy. Among its most serious consequences in the ethical
      domain has been the weakening of the therapist's guarantee of absolute
      confidentiality to the patient. Managed care has further compounded the ethical
      dilemma by imposing a need to choose between the interests of patients and the
      organizations from which therapists receive remuneration. In their efforts to
      ensure parity coverage for psychotherapy, therapists need to respond to certain
      questions about their claims that their work promotes both individual welfare and
      the common good. Questions include the professional qualifications for skillful
      practice of psychotherapy, the evidence for its efficacy, the delimitation of the
      conditions properly treated by psychotherapy, and the extent to which these
      conditions fall within the medical model and thus satisfy the criterion of
      medical necessity. I conclude that, in spite of the efforts needed to maintain
      ethical standards, the "ethical revolution" that I have witnessed has enhanced
      the integrity and value of psychotherapy, both for its practitioners and for the
      public that they serve.

PMID- 8886231
TI  - Lessons to be learned from the study of sexual boundary violations.
AB  - The study of sexual boundary violations, through the actual evaluation and
      treatment of therapists who have engaged in sexual misconduct, reveals that all
      of us are potentially vulnerable to violations of this nature. A number of
      lessons can be learned from the detailed examination of these cases. These
      lessons include the following: (1) There is a difference between the conscious
      and unconscious intent of the therapist. (2) "Love" in the therapeutic setting is
      fraught with problems, including the fact that it is often used as a defense
      against the therapist's own aggression. (3) Supportive therapy and boundaryless
      therapy often become confused when a therapist switches from an expressive to a
      supportive approach. (4) The thoughts, feelings, and behaviors that a therapist
      would most like to keep secret from a supervisor or consultant are the most
      important issues to discuss with that supervisor or consultant. These
      observations have a number of implications for prevention. Matters of technique
      are inevitably conflated with issues of ethical principles so that the teaching
      of ethics must include discussions of transference, countertransference, and the
      use of third parties, such as supervisors or consultants, to assist the therapist
      in the monitoring of professional boundaries.

PMID- 8886232
TI  - Ethical issues in the search for repressed memories.
AB  - Currently, concepts of repression and dissociation are in flux. It has been
      pointed out that there is no scientific evidence for the occurrence of repression
      and that the whole notion is anecdotal. Dissociation, which is offered as an
      alternative to repression, cannot logically be held to operate without a motive
      force, as Freud argued, or a weakness of the organism, as Janet proposed. The
      concepts have been applied particularly to the idea that early childhood
      experience could be repressed but recovered many years later. This claim is at
      variance with established knowledge concerning human memory. Practices of subtle
      and overt suggestion, employed in recovered-memory treatments, give rise to a
      false-memory syndrome in which individuals, who have undergone various levels of
      suggestion, accuse their parents and others of childhood sexual abuse. The common
      phenomenon of childhood sexual abuse is contaminated by many cases that may be
      regarded on strong grounds as being false and have been retracted in more than
      1,000 instances. Repressed-memory (RM) treatment is also at variance with
      traditional psychotherapy, which does not encourage confrontation on the basis of
      uncorroborated information; moreover, many cases of RM therapy seem to result in
      deterioration. Unlike traditional psychotherapy, some RM practitioners strongly
      encourage patients to hate individuals in their family circle. The consequences
      of these developments, the need for informed consent, and the development of
      legislative initiatives to challenge RM therapy are noted. The impact of these
      therapies and proposed legislation upon regular psychotherapy and psychiatry is
      outlined.

PMID- 8886233
TI  - Jokes as a projective technique: the humor of psychiatric patients.
AB  - Jokes were obtained from psychiatric patients during the course of diagnostic
      testing and interviewing. The material was subjected to a content analysis which
      included the nature of the main characters and their relationships, the
      situations presented, and the major overt and concealed themes. This paper
      discusses and gives examples of the projective and psychodynamic value of humor
      in professional practice. The jokes helped in the understanding of diagnosis,
      symptoms, and basic conflicts. They provided guidelines for treatment and the
      treatment plan. They depicted the struggles of the participants to cope with
      relationships, problems, crises, and change. None of these struggles were unique
      to patients. Jokes cut through professional distinctions and diagnostic
      classifications, and present the person behind the label. They reflect the nature
      of the self especially in its more troubling and problematic aspects; yet they
      also reveal the healthy and intact part of the person. Jokes were valuable as a
      projective method because they constituted a non-threatening vehicle for
      revealing otherwise threatening and concealed truths about the person; they
      communicate those aspects of the human condition that are most anxiety provoking;
      and last, but not least, they end the interview on an enjoyable and positive
      note.

PMID- 8886234
TI  - Our time is up: forced terminations during psychotherapy training.
AB  - Forced terminations are a powerful experience for both patients and for
      residents. Such terminations often resemble earlier losses to patients, who may
      react with particular defense constellations, changes in symptoms, and profound
      reactions to the therapist. Similarly, prominent countertransference may manifest
      in attempts by residents to deny their importance to patients, to project
      reactions onto their patients, and to alter the therapy relationship. More
      intense therapy relationships usually require termination announcements months in
      advance. How much will be revealed to patients may best be determined prior to
      the announcement. Payments, gifts, subsequent contact, transfer to another
      therapist, and concluding therapy comments need evaluation of what is in the
      patient's best interest and may require creative approaches deviating from
      traditional therapy practices. This discussion reviewed reactions of patients and
      residents to forced termination, addressed the pragmatic issues confronting the
      resident, provided clinical vignettes illustrating peculiarities of forced
      terminations, and listed recommendations to assist the departing resident. Forced
      terminations afford powerful opportunities for contending with abandonment,
      disappointment, and loss directly in the therapy. While these experiences are
      certainly not comfortable, they can be used constructively to benefit patients if
      the issues surrounding the forced termination are carefully considered and
      addressed within the therapy.

PMID- 8886235
TI  - The creative aspect of dynamic psychotherapy: parallels between the construction
      of experienced reality in the literary and the psychotherapeutic process.
AB  - Aesthetic experience and psychotherapeutic practice are compared. Beginning with
      the assumption that memories, imaginings and feelings are aesthetic categories,
      it is shown that aesthetic experience is elementary in the shaping and
      structuring of the experiences of human beings, both in psychotherapeutic
      communication and in the process of production and reception in literature. The
      aesthetic shaping of events into integrated experiences in the course of the
      therapeutic encounter might have a healing effect in its own right. To this
      extent, the therapeutic process should be regarded both as a joint process of
      creation and as a process of interpretation. As in writing and reading a literary
      work of art, the therapeutic process consists of special functions of
      productivity/poiesis, receptivity/aesthesis, and communicative
      interaction/catharsis. The psychic mechanism of projective identification may
      help us understand this emotional and cognitive interchange psychodynamically.
      Further graphic associations and visual imaginings that arise in the patient and
      in the therapist are considered, like literary works of art, to function as
      "transitional objects." These creations of patient and therapist, artist and
      recipient serve to consolidate formerly nonintegrated and therefore pathogenic
      experiences. A fruitful psychodynamic work is always situated in the tense
      relationship between the aesthetic shaping of emotions and the scientific
      interpretation of inner and outer facts.

PMID- 8886236
TI  - Endothelin-induced electrical activity and calcium dynamics in vascular smooth
      muscle cells: a model study.
AB  - A model is proposed to describe the electrical activity and intracellular calcium
      dynamics of vascular smooth muscle cells (SMC) induced by endothelin (ET1). The
      conductance of the nonselective channels (NSCs), proportional to the ET1-receptor
      complex (ET . R), is intracellular calcium dependent. Inositol (1,4,5)
      trisphosphate (IP3) produced by ET1 releases Ca2+ from the IP3-sensitive Ca2+
      store. The transient increase of intracellular Ca2+ triggers the release of Ca2+
      from the Ca(2+)-sensitive store by a Ca(2+)-induced Ca2+ (CICR) mechanism and
      activates the Ca(2+)-activated K+ current (IK,Ca). The inward current (Iin) via
      the NSC can depolarize the cell to a level at which the L-type Ca2+ current
      becomes activated (ICa). The level of depolarization is determined by the
      relative amplitude of (Iin + ICa + IK,Ca) and the voltage- and time-dependent K+
      current. The model simulations show that (a) in cells without a CICR mechanism,
      short-lasting stimulation by ET1 elicits higher membrane potential and Ca2+ than
      long-lasting stimulation; (b) in cells with or without a CICR mechanism, a
      reduction of normal membrane capacitance (1 muf/cm2) results in either
      significant and sustaining or oscillatory membrane potential and intracellular
      calcium concentration. The applicability of the model to the study of electrical
      activity and calcium dynamics associated with hypercholesterolemia is discussed.

PMID- 8886237
TI  - Computational simulations of mitral regurgitation quantification using the flow
      convergence method: comparison of hemispheric and hemielliptic formulae.
AB  - Mitral regurgitation results from the incomplete closure of the mitral valve, and
      the noninvasive diagnosis of this disease remains an important clinical goal. In
      this study, steady flow computer simulations were used to evaluate flow
      convergence method for flow rate estimation. The hemispheric and hemielliptic
      formulae were compared for accuracy in the presence of complicating factors such
      as ventricular confinement, orifice shape, and aortic outflow. Results showed
      that in the absence of aortic outflow and ventricular confinement, there was a
      plateau zone where the hemispheric formula approximated the true flow rate,
      independent of orifice shape. However, in the presence of complicating factors
      such as aortic outflow and ventricular confinement, there was no clear zone where
      the hemispheric formula could be applied. The hemielliptic formula, however,
      worked in all cases, regardless of chamber size or magnitude of aortic outflow.
      Therefore, application of the hemielliptic formula should be considered in future
      clinical studies.

PMID- 8886238
TI  - Ex vivo biomechanical behavior of abdominal aortic aneurysm: assessment using a
      new mathematical model.
AB  - Knowledge of the biomechanical behavior of abdominal aortic aneurysm (AAA) as
      compared to nonaneurysmal aorta may provide information on the natural history of
      this disease. We have performed uniaxial tensile testing of excised human
      aneurysmal and nonaneurysmal abdominal aortic specimens. A new mathematical model
      that conforms to the fibrous structure of the vascular tissue was used to
      quantify the measured elastic response. We determined for each specimen the yield
      (sigma y) and ultimate (sigma u) strengths, the separate contribution to total
      tissue stiffness by elastin (EE) and collagen (EC) fibers, and a collagen
      recruitment parameter (A), which is a measure of the tortuosity of the collagen
      fibers. There was no significant difference in any of these mechanical properties
      between longitudinal and circumferential AAA specimens, nor in EE and EC between
      longitudinally oriented aneurysmal and normal specimens. A, sigma y, and sigma u
      were all significantly higher for the normal than for the aneurysmal group: A =
      0.223 +/- 0.046 versus A = 0.091 +/- 0.009 (mean +/- SEM; p < 0.0005), sigma y =
      121.0 +/- 32.8 N/cm2 versus sigma y = 65.2 +/- 9.5 N/cm2 (p < 0.05), and sigma u
      = 201.4 +/- 39.4 N/cm2 versus sigma u = 86.4 +/- 10.2 N/cm2 (p < 0.0005),
      respectively. Our findings suggest that the AAA tissue is isotropic with respect
      to these mechanical properties. The observed difference in A between aneurysmal
      and normal aorta may be due to the complete recruitment and loading of collagen
      fibers at lower extensions in the former. Our data indicate that AAA rupture may
      be related to a reduction in tensile strength and that the biomechanical
      properties of AAA should be considered in assessing the severity of an individual
      aneurysm.

PMID- 8886239
TI  - Regional three-dimensional geometry of the normal human left ventricle using cine
      computed tomography.
AB  - The aim of this study is to provide accurate three-dimensional measurements of
      left ventricular geometrical indices in relation to regional myocardial function.
      The analysis of the three-dimensional regional geometry and function of left
      ventricles of ten normal human volunteers is based on three-dimensional
      reconstructions of the left ventricle from cine computed tomography images, at
      end diastole and end systole, demonstrating normal left ventricular spatial,
      geometrical, and functional variability. Regional wall thickness, curvature and
      surface normals, as well as wall thickening and endocardial wall motion, are
      calculated and mapped for the entire left ventricle. The circumferential
      asymmetry of the left ventricle is reflected by the smaller circumferential and
      meridional curvatures at the septum. Thickening is highest at the anterior and
      lateral walls. Longitudinally, circumferential curvature increases toward the
      apex, whereas both wall thickness and wall thickening at end systole are largest
      at the midventricular level, decreasing toward the apex and base. This study
      describes the circumferential and apex-to-base variations in regional left
      ventricular geometric parameters of the normal human left ventricle, using three
      dimensional imaging and analysis.

PMID- 8886240
TI  - A piconewton force transducer and its application to measurement of the bending
      stiffness of phospholipid membranes.
AB  - The bending stiffness of a phospholipid bilayer (Kc) was measured by forming thin
      bilayer cylinders (tethers) from giant phospholipid vesicles. Based on the
      balance of forces, the tether force was expected to be proportional to the square
      root of the membrane tension, with a constant of proportionality containing Kc.
      The membrane tension was controlled via the aspiration pressure in a micropipette
      used to hold the vesicle. The force on the tether was generated by an
      electromagnet acting on a paramagnetic bead attached to the vesicle surface. The
      magnitude of the force was determined from measurements of the magnet current,
      which was adjusted to maintain the position of the bead. Measurements were
      performed on vesicles composed of stearoyl-oleoyl-phosphatidylcholine plus 5% (by
      mole) biotinylated phosphatidylethanolamine to mediate adhesion to streptavidin
      coated beads. From each vesicle, tethers were formed repeatedly at different
      values of the membrane tension. The expected relationship between membrane
      tension and tether force was observed. The mean value of Kc for 10 different
      vesicles was 1.17 x 10(-19) J (SD = 0.08 x 10(-19) J). The precision of these
      data demonstrates the reliability of this approach, which avoids uncertainties of
      interpretation and measurement that may be associated with other methods for
      determining Kc.

PMID- 8886241
TI  - Magnetic stimulation of the nervous system: induced electric field in unbounded,
      semi-infinite, spherical, and cylindrical media.
AB  - Knowledge of the electric field that is induced in the brain or the limbs is of
      importance in magnetic stimulation of the nervous system. Here, an analytical
      model based on the reciprocity theorem is used to compare the induced electric
      field in unbounded, semi-infinite, spherical, and cylinder-like volume
      conductors. Typical stimulation coil arrangements are considered, including the
      double coil and various orientations of the single coil. The results can be used
      to determine when the influence of the boundaries is negligible enough to allow
      the use of more simplified geometries.

PMID- 8886242
TI  - Genealogy and geographical distribution of CFTR mutations in Saguenay Lac-Saint
      Jean (Quebec, Canada).
AB  - Saguenay Lac-Saint-Jean (SLSJ), a region located in northeastern Quebec, has a
      high incidence of cystic fibrosis (CF). During the past few years the majority of
      the CF patients have been genotyped. The geographical distribution of the birth
      places of the patients and obligate carriers of the 621 + 1G-->T, the A455E and
      the delta F508 mutations (which accounted for 89% of the CF chromosomes) showed
      differences that can be explained by some degree of isolation but also by
      differential migration. The mean inbreeding and kinship coefficients were higher
      among the various CFTR mutation groups than in the general population. An
      ancestor couple common to most of the A455E carriers was identified. These data
      further substantiate the role of founder effect in the CF population of SLSJ.

PMID- 8886243
TI  - Obesity and the risk of toxaemia of pregnancy.
AB  - The purpose of the present study was to examine the relationship between severe
      pre-eclampsia/eclampsia (toxaemia) and obesity. We collected sociodemographic,
      anthropometric, medical and pregnancy outcome data from the hospital records of
      248 Israeli women diagnosed with either pregnancy-induced or chronic
      hypertension, and compared these data to a control group of 236 women. Univariate
      analysis showed that while there exists a statistically significant positive
      association between obesity and hypertension (both pregnancy-induced and chronic)
      obesity presents no added risk to the development of toxaemia. Furthermore, we
      found a significant decrease in the rate of obesity among primigravid versus
      multigravid mothers with toxaemia superimposed on pregnancy-induced hypertension.
      On the other hand, primigravid mothers with PIH were at an increased risk of
      developing toxaemia as compared to multigravid women. These results suggest that
      obesity is not a significant factor in the development of toxaemia.

PMID- 8886244
TI  - Dermatoglyphics of the Chorote indians and their relationships with other
      inhabitants of the Gran Chaco.
AB  - The present report deals with digital and palmar dermatoglyphics of a sample of
      98 Chorote indians, collected in the north of Argentina, in the Gran Chaco
      region. Bimanual dimorphism was observed in males and females, both in finger and
      in palmar variables. Significant differences between sexes appear only in digital
      ridge counts and in the combined incidence of the four pattern types the Chorote,
      in general, show low sexual dimorphism. Univariate comparisons carried out with
      other tribes of the Gran Chaco (Chiriguano, Pilaga, Mataco, and Toba) indicate
      statistically significant differences between these and the Chorote, both in
      males and females. The greatest differences were found in relation to the Mataco,
      who belong to the same linguistic family as the Chorote. Probable explanations
      for these differences are proposed.

PMID- 8886245
TI  - A comparative study of foot morphology between Filipino and Japanese women, with
      reference to the significance of a deformity like hallux valgus as a normal
      variation.
AB  - In order to investigate the shape and size differences in feet caused by daily
      footwear, a comparative study was conducted on foot morphology in two
      populations. The data from six measurements in general physique and 18
      measurements in the feet and their contours were obtained from 34 Filipino women
      in Isabela Province and 40 Japanese women in Tokyo. Despite the fact that the
      Tokyo women had larger physique than the Isabela women, there were no significant
      differences in foot size between two groups. Both relative size of foot for
      general physique and intragroup deviation of foot proportion were larger in the
      Isabela women than those in the Tokyo women. In comparing foot contour, many
      measurements relating particularly to foot proportion, represented by angles,
      showed significant differences between the two groups. In gross observation some
      of the Isabela women showed marked deformity of the grand toe to the lateral
      side, "like a hallux valgus' without any complaints. In principal-component
      analysis (PCA), CP1 was interpreted as size factor, CP2 was considered as
      position of foot axis, CP3 and CP4 were estimated as degree of angle between foot
      axis and ball axis. Means of individual score by PCA showed a completely inverse
      pattern between Isabela and Tokyo women. The differences in foot morphology
      recognized in these two groups were considered from the point of view of
      differences of daily footwear, which have not changed in the Philippines but have
      changed dramatically in Japan since World War II. We concluded that the deformity
      like a hallux valgus, frequently found in previous generations of Japanese who
      used to wear traditional footwear, geta and zori, must have been a healthy
      deformity, however, the pathological deformity hallux valgus is observed only in
      the Isabela women of today.

PMID- 8886246
TI  - Energy metabolism: overview of recent methods used in human studies.

PMID- 8886247
TI  - Comparison of content and distribution of human milk gangliosides from Spanish
      and Panamanian mothers.
AB  - The lactational changes in content and distribution of gangliosides in human milk
      from Spanish and Panamanian mothers delivering term newborns were studied. There
      were no statistically significant differences in the concentration of
      gangliosides between Spanish and Panamanian milk. The ganglioside content
      expressed as a function of total milk lipids tended to decrease as lactation
      progressed in both types of milk. There was a significant correlation (r =
      0.5896; p = 0.0062) between ganglioside and total lipid contents in Panamanian
      milk. However, in Spanish milk, the correlation was not significant (r = 0.1516;
      p = 0.3439). We did not detect important differences in the relative
      concentrations of individual gangliosides during lactation among milk samples
      from Spanish and Panamanian mothers. For both of them, GD3 was the most abundant
      ganglioside in colostrum, whilst in mature milk it was GM3.

PMID- 8886248
TI  - Elimination of meat, fish, and derived products from the Spanish-Mediterranean
      diet: effect on the plasma lipid profile.
AB  - The effect of eliminating all animal (meat and fish) products except eggs and
      milk products from the current Spanish-Mediterranean diet was studied in 14
      healthy subjects. This dietary manipulation decreased saturated and
      monounsaturated fat, protein, and cholesterol intakes. During the 2-month
      intervention period, a decrease in total plasma cholesterol concentrations (4.53
      +/- 0.13 vs. 4.29 +/- 0.13 mmol/l, p < 0.05) was observed, mostly as a result of
      decreased high-density lipoprotein cholesterol levels (1.66 +/- 0.08 vs. 1.47 +/-
      0.08 mmol/l, p < 0.05). The decrease in low-density lipoprotein cholesterol
      levels (2.51 +/- 0.15 vs. 2.43 +/- 0.13 mmol/l) did not reach statistical
      significance. Nevertheless, there was a significant association between the
      decrease in cholesterol intake and the decrease in low-density lipoprotein
      cholesterol levels (r = 0.719, p < 0.01). The decrease in protein intake was also
      correlated with the decrease in total cholesterol levels (r = 0.629, p < 0.05).
      Body weight and lean body mass were not modified during the study. Maximal
      aerobic power and maximal oxygen consumption were not significantly affected by
      the diet manipulation. IN CONCLUSION: a 2-month change from the current Spanish
      Mediterranean diet to an ovolactovegetarian diet in young healthy persons
      decreases total plasma cholesterol levels, but mainly due to a decrease in high
      density lipoprotein cholesterol levels.

PMID- 8886249
TI  - Changes in plasma insulin, enterostatin, and lipoprotein levels during an energy
      restricted dietary regimen including a new oat-based liquid food.
AB  - The changes in plasma insulin, enterostatin, lipid, and glucose levels during
      weight reduction were studied in 32 subjects having a body mass index of 25-35.
      The 31 subjects who completed the study followed for 23 weeks an energy
      restricted dietary regimen which included a new oat-based soup as the main meal
      once or twice daily. The intake of energy decreased from 8.9 to 6.2 MJ/day from 0
      to 22 weeks, the energy percentage from fat decreased from 35 to 30%, and the
      intake of dietary fiber increased from 21 to 25 g/10 MJ. The body weight
      decreased from 83 to 78 kg after 6 weeks and to 77 kg after 23 weeks. Plasma
      glucose had decreased significantly from 5.4 to 5.2 mmol/l, and plasma insulin
      from 122 to 98 pmol/l after 23 weeks. In contrast, the plasma enterostatin
      concentration did not vary significantly over five sampling times, the mean
      values ranging from 25 to 30 nmol/l. Plasma cholesterol declined from 5.6 to 5.2
      mmol/l, low-density lipoprotein cholesterol from 3.8 to 3.3, and plasma
      triglycerides from 1.5 to 1.3 mmol/l from 0 to 23 weeks. High-density lipoprotein
      cholesterol increased from 1.1 to 1.3 mmol/l. It is concluded that an energy
      restricted regimen leading to lower plasma insulin, triglyceride, and low-density
      lipoprotein cholesterol levels did not significantly affect the plasma
      enterostatin concentration in overweight subjects. A new oat-based liquid food as
      a part of the dietary regimen was well tolerated.

PMID- 8886250
TI  - Total, free, short-chain and long-chain acyl carnitine levels in Arabian camel
      milk (Camelus dromedarius).
AB  - The total, free, short-chain acyl and long-chain acyl carnitine levels were
      measured in milk of the Arabian camel (Camelus dromedarius). Significant
      variation in carnitine concentrations were observed in milk of the camel when
      compared with other mammalian milk species. The result shows that Arabian camel
      milk possesses a higher than usual concentration of the average percent
      contribution of free carnitine to total carnitine that is found in most mammalian
      milk species. A higher proportion of total carnitine was found in camel milk when
      compared with cow, human milk and milk formulas, however, it is lower when
      compared with sheep and goat milk. The higher carnitine content and a higher
      proportion of total carnitine in milk of the Arabian camel suggest an adaptive
      mechanism that could be common to desert mammalian species.

PMID- 8886251
TI  - The nutritional effect of a-linolenic acid-rich emulsion with total parenteral
      nutrition in a rat model with inflammatory bowel disease.
AB  - The purpose of this study was to investigate the nutritional effect of perilla
      oil emulsion (POE) in a rat model with inflammatory bowel disease (IBD) induced
      by 2,4,6-trinitrobenzenesulfonic acid. POE and soybean oil emulsion (SOE) were
      infused at 20% of nonprotein energy during 7 days' total parenteral nutrition
      (TPN). After infusion of test solutions, body weight gain and cumulative nitrogen
      balance in the POE group were significantly higher than those in the fat-free TPN
      (FF) group after infusion of test solutions. Moreover, those in the POE group
      were higher than those in the SOE group, but no significant difference was
      observed between the POE and SOE groups. In the POE group, total cholesterol and
      phospholipid concentration in the plasma was significantly decreased compared
      with the FF and SOE groups. Triglyceride concentration in the plasma did not
      significantly differ between the POE, SOE and FF groups. Plasma lipid peroxide
      concentration in the POE group was significantly lower than that in the SOE
      group, but it was not different from the FF group. In fatty acid composition in
      the plasma total lipids, linoleic acid in the POE and SOE groups and alpha
      linolenic acid in the POE group were significantly increased compared with those
      in the FF group. Arachidonic acid (AA) in the POE and FF groups were
      significantly decreased compared with that in the SOE group. Otherwise,
      eicosapentaenoic acid (EPA) in the POE group was significantly increased compared
      with that in the SOE and FF groups. EPA/AA ratio in the POE group was
      significantly increased compared with the SOE group. The thickness and damage
      score of the colon were significantly depressed in the POE group compared with
      the SOE group. These results suggest that POE has a superior nutritional effect
      and improves inflammation in the IBD.

PMID- 8886252
TI  - Red blood cell and tissue phospholipid fatty acid profiles of weanling rats fed
      infant formula fat blends containing soy and/or corn oil.
AB  - Soy oil or corn oil may be employed to provide essential fatty acids in infant
      formulas. Both of these sources are high in linoleic acid; soy oil contains
      modest levels of alpha-linolenic acid, while corn oil contains very low levels of
      this essential omega 3 fatty acid. We examined the omega 3 long-chain
      polyunsaturated fatty acid (LCP) accretion in red blood cells, liver, and brain
      phospholipids of rats on diets containing infant formula fat blends with
      essential fatty acids provided from soy and/or corn oil. Although modest
      alterations occurred in the red blood cell omega 3 LCP fatty acid status,
      substantially larger changes were noted in liver LCP profiles. Due to the
      relatively mature nature of the rats employed in this experiment, no alterations
      were noted in brain fatty acid profiles. In conclusion, we have observed
      substantial tissue differences in animals fed soy or corn oil containing diets.
      It appears that corn oil is inappropriate for use in infant formulas.

PMID- 8886253
TI  - Age-dependent doses to members of the public from intake of radionuclides: Part
      5. Compilation of ingestion and inhalation dose coefficients.

PMID- 8886254
TI  - In vitro effect of Escherichia coli on human sperm acrosome reaction.
AB  - Escherichia coli are known to reduce human sperm motility. The purpose of the
      present study was to examine whether these bacteria may also affect the acrosome
      reaction, which is another important sperm function. The acrosome reaction was
      determined in spermatozoa from 29 fertile men by triple stain after 3-h
      incubation at 37 degrees C with 2 x 10(6) E. coli/mL or without bacteria
      (control). Each sample was treated with 0.1% DMSO (spontaneous acrosome reaction)
      or calcium ionophore A23187 (induced acrosome reaction) for 1 h at 37 degrees C.
      The inducibility of the acrosome reaction was significantly lower in semen
      samples pretreated with E. coli than in the control samples (9.8 +/- 4.2% vs.
      12.7 +/- 5.3%; p < .05). The results demonstrate that E. coli affect the
      inducibility of the acrosome reaction in vitro and may impair the fertilizing
      capacity of human spermatozoa.

PMID- 8886256
TI  - Prognostic value of the strict criteria: an Argentinian experience.
AB  - The prognostic value of normal sperm morphology, evaluated according to the
      strict criteria, was prospectively assessed. The study included 112 IVF cycles.
      The percentage normal sperm morphology of the semen samples used in each cycle
      was determined and assigned to one of three prognostic groups; P-pattern (< 4%
      normal forms), G-pattern (5-8% normal forms), and N-pattern (> 8% normal forms).
      The fertilization, grade 4 embryo attainment, and pregnancy rates were compared
      between the three groups. The fertilization rate of the N-pattern group (83.7%)
      was significantly higher than that of the G-pattern (59.65%) and the P-pattern
      (22.58%) groups. The grade 4 embryo attainment rate was only significantly
      different between the N-pattern (23.38%) and the P-pattern (4.76%) groups. No
      pregnancy was obtained in the P-pattern group compared to a pregnancy rate per
      transfer of 23.08% in the N-pattern group. This study reaffirms the
      interlaboratory reproducibility and the prognostic value of normal sperm
      morphology.

PMID- 8886255
TI  - Characteristics of calcium ion influx induced by human follicular fluid in
      individual human sperm.
AB  - The mechanism of Ca2+ influx into human spermatozoa was investigated. Human
      follicular fluid (hFF), which contains progesterone, stimulated an increase in
      the concentration of intracellular free Ca2+ ([Ca2+]i) as measured by
      fluorescence spectroscopy using Fura-2/AM. The technique allowed the measurement
      of [Ca2+]i in individual, motile spermatozoa, by improvement of the previous
      methods. The role of Ca2+ channels was investigated using selective blocking
      agents. Neither blockade of L-type channels with verapamil or lanthanum (La3+)
      nor blockade of N-type channels with omega-conotoxin affected the hFF-stimulated
      increase in [Ca2+]i. Blockade of T-type channels with either nickel (Ni2+) or
      amiloride significantly reduced the hFF-stimulated increase in [Ca2+]i and
      amiloride significantly decreased baseline [Ca2+]i. Incubation of sperm in Na(+)
      free medium did not affect [Ca2+]i, indicating that Na+/Ca2+ exchange has no
      major role in Ca2+ influx. The results suggest that calcium influx induced by hFF
      occurs via T-type voltage-independent Ca2+ channels. The method described allows
      accurate measurement of [Ca2+]i in individual, motile human spermatozoa.

PMID- 8886257
TI  - Chronobiological fluctuations in semen parameters with a constant abstinence
      period.
AB  - This study examined the seasonal variation in three semen parameters (total sperm
      count, % grade a progressive motility and sperm morphology according to strict
      criteria) with an identical abstinence period of 24 h. A total of 340
      spermiograms of 107 different men enrolled in an intrauterine insemination (IUI)
      program were examined. To reduce variation due to interindividual disparities in
      semen quality, differences of each test result from the mean value obtained for
      that individual were analyzed. Mean values resulted from at least 3 observations
      during different IUI cycles. Using ANOVA and spectral analysis, no differences in
      semen parameter results in function of the month of the year were observed. The
      lack of any significant periodicity may be explained by the large biological
      variation for individual semen parameters and/or the lack of significant
      differences regarding light exposure and temperature between summer and winter
      months in moderate climates.

PMID- 8886258
TI  - Azoospermia: clinical, hormonal, and biochemical investigation.
AB  - The aim of this study was to evaluate the clinical, hormonal and biochemical
      characteristics of infertile men with azoospermia. A total of 187 azoospermic out
      of 2610 infertile men (7.2%) were studied. Mean testicular volume and basal
      plasma levels of FSH were the most useful parameters concerning the evaluation of
      azoospermia. Basal plasma levels of LH and T were useful only in azoospermic men
      with hypogonadism, whereas plasma PRL levels, semen volume, and seminal plasma
      fructose levels were not found to be of common use except in selected cases.

PMID- 8886259
TI  - Combination of direct swim-up technique and discontinuous Percoll gradient
      centrifugation for sperm preparation of oligoasthenozoospermic samples.
AB  - Sperm recovery for assisted reproduction in oligoasthenozoospermic patients is
      not satisfying either by the swim-up technique or by Percoll gradient
      centrifugation, and no single technique is constantly preferred. The design of
      this study was to evaluate the effects of combining the two methods on improving
      the efficacy of sperm preparation in these poor samples. For each semen sample, 1
      mL was treated with a combination method, which used direct swim-up technique to
      recover motile sperm swimming to the supernatant, and then the residual semen was
      subjected to two-layer discontinuous Percoll gradient procedure for further
      recovery of motile sperm. Another 1 mL was prepared with two-layer discontinuous
      Percoll gradient centrifugation alone for comparison. Parameters measured
      included sperm concentration, number of progressively motile sperm, percentage of
      progressive motility, percentage of motile sperm recovery, amount of debris,
      percentage of normal forms according to Kruger's strict criteria, and motion
      characteristics of sperm using computer-aided motility analysis. The results of
      30 oligoasthenozoospermic samples demonstrated that the combination method
      achieved a significantly greater recovery of motile sperm than the two-layer
      discontinuous Percoll gradient centrifugation did (43.2 +/- 19.7% vs. 32.2 +/-
      14.3%, p < .05). The percentage of progressive motility was higher in the samples
      of the combination method than in those of Percoll gradient centrifugation alone,
      but the difference was not significant (63.7 +/- 21.8% vs. 58.7 +/- 20.1%). The
      debris of semen was removed equally well by both methods. The percentage of
      normal forms as well as motion characteristics, including curvilinear velocity,
      straight-line velocity, mean amplitude of lateral head displacement, and
      linearity, were similar in the samples treated by these two procedures. The
      combination of the direct swim-up technique and discontinuous Percoll gradient
      centrifugation combines the advantages of each procedure and results in greater
      recovery of motile sperm in oligoasthenozoospermic samples.

PMID- 8886260
TI  - Effect of different types of textiles on male sexual activity.
AB  - The effect of different types of textile underpants on sexual activity was
      studied in 50 men. All the subjects were potent and sexually active. They were
      divided into 5 equal groups: 4 test and 1 control. Each of the 4 test groups were
      dressed in one type of textile underpants made of either 100% polyester, 50/50%
      polyester/cotton mix, 100% cotton, or 100% wool. Sexual behavior was assessed
      before and after 6 and 12 months of wearing the pants, and 6 months after their
      removal. Behavioral response was rated as potent if the subject's penis became
      erect, entered the vagina, and ejaculated. The rate of potent intromission (I) to
      mounts (M) (I/M ratio) was determined. The electrostatic potentials (EP)
      generated on the penis and scrotum were measured by an electrostatic
      kilovoltmeter. The I/M ratio at 6 and 12 months of wearing the polyester and
      polyester/cotton mix pants was significantly reduced compared to the pretest
      levels and the controls (p < .001). The reduction was more manifest in the pure
      polyester than in the polyester/cotton mix group, and at the 12-month than at the
      6-month examination. The I/M ratio of the cotton and wool groups showed
      insignificant changes during the study period. Six months after removal of the
      underpants, the I/M ratio had returned to the pretest levels in the two groups
      that had worn polyester-containing pants. The polyester-containing pants
      generated EP, which may induce electrostatic fields in the intrapenile structures
      and could explain the diminished sexual activity. The cotton and wool textiles
      did not generate EP. Thus, polyester underpants could have an injurious effect on
      human sexual activity.

PMID- 8886261
TI  - Etiopathogenesis of cryptorchidism and male infertility.
AB  - A retrospective study was performed 2.60 +/- 1.14 years after ochidopexy on 124
      patients with cryptorchidism. Complex spermatological, hormonal, and
      histomorphological investigations were carried out which demonstrated the
      existence of disturbances in the exo- and endocrine functions of the testes of
      these patients. The results juxtaposed to the ages when the orchidopexy was
      accomplished revealed the necessity of early surgical intervention prior to 5
      years of age. After this age there were severe changes in the histomorphological
      characteristics of the testicular tissue.

PMID- 8886262
TI  - Sertoli cell conditioned media modulate the androgen biosynthetic pathways in rat
      Leydig cell primary cultures.
AB  - Increasing evidence suggests the presence of local modulators that contribute to
      testicular function regulation in rats. The seminiferous tubules and Sertoli cell
      factors influence the steroidogenic activity of Leydig cells. Addition of Sertoli
      cell conditioned media to primary cultures of adult rat Leydig cells produces in
      a dose-dependent manner an inhibition of testosterone production with a
      concomitant decrease in the C21 delta 4-intermediates of the steroidogenic
      pathway, modifying the C21/C19 ratios in normal cells. The nature and mechanisms
      of action of this putative modulating activity are currently under study.

PMID- 8886263
TI  - Identification of a rabbit epididymal protein gene.
AB  - A protein designated as BE-20 was purified from cauda epididymal fluid of the
      rabbit by preparative polyacrylamide gel electrophoresis and HPLC on a mono Q
      HR5/5 anion exchange column. The purified protein migrated with an estimated Mt
      of 20,000 when analyzed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. The amino acid sequence of the N-terminus of the BE-20 protein
      was determined. The initial eight amino acid residues were His-Gly-Ala-Asp-Lys
      Pro-Gly-Val. The corresponding 23 mer oligonucleotide (5'-CATGGCGCTGACAAGCCTGGGGT
      3') was synthesized and used as sense primer with rabbit epididymal mRNA as
      template in the RT-PCR system. The purified BE-20 cDNA consisted of 499 bp with
      an open reading frame of 285 bp encoding a deduced polypeptide composed of 95
      amino acids. The BE-20 cDNA had 78.5% identity in 479 bp overlap with human
      epididymis-specific HE4 cDNA. The amino acid sequences of the initial 30 amino
      acid residues of the N-terminus of the purified protein and the deduced
      polypeptides were as follows: N-His-Gly-Ala-Asp-Lys-Pro-Gly-Val-Cys-Pro-Gln-Leu
      Ser-Ala-Asp-Leu-Asn-Cy s- Thr-Gln-Asp-Cys-Arg-Ala-Asp-Gln-Asp-Cys-Ala-Glu. The
      deduced polypeptide contained 16 cysteine residues and had partial sequence
      homology with proteins belonging to the four-disulfide core family of
      extracellular proteinase inhibitors. The BE-20 protein may play a role in sperm
      maturation and/or capacitation.

PMID- 8886264
TI  - Immobilization and stabilization of horseradish peroxidase isoforms.
AB  - Purified anionic and cationic isoforms of horseradish peroxidase (HRP)
      immobilized by coupling the amino acid side-chain amino groups and/or
      carbohydrate moieties to Sepharose have been studied for their resistance to
      denaturation. The isoforms were treated with periodate followed by
      ethylenediamine to generate additional amino groups in the glycosyl residues. The
      immobilized preparations were: Preparation I (Sp-aHRP, Sp-cHRP), in which HRP was
      covalently immobilized via side-chain amino groups exclusively; Preparation II
      (Sp-NHaHRP, Sp-NHcHRP), in which periodate and ethylenediamine-treated HRP was
      covalently immobilized via side-chain amino groups and amino groups incorporated
      into glycosyl residues. HRP isoforms in preparation II lacked about 33-55%
      carbohydrate. Both strategies of immobilization induced significant stabilization
      against denaturation. Inclusion of 2 mM calcium enhanced isoenzyme stability
      significantly.

PMID- 8886265
TI  - The interactions of alpha 2HS glycoprotein with metalloproteinases.
AB  - The objective of the present analyses was to determine whether matrix
      metalloproteinases interact with alpha 2HS glycoprotein, the human homologue of
      bovine fetuin. Alpha 2HS glycoprotein was incubated with metalloproteinases at
      1:1 and 1:10 molar ratios. The serum glycoprotein was completely degraded by
      gelatinase-A and matrilysin at the higher enzyme concentration after an overnight
      incubation at 37 degrees C. The data show that gelatinase-A, matrilysin and
      gelatinase-B do interact with alpha 2HS glycoprotein and that gelatinase-B
      associates most tightly with the serum glycoprotein.

PMID- 8886266
TI  - Phosphorylation of native and truncated isoforms of protein tau by the double
      stranded DNA-dependent protein kinase (DNA-PK) shows that the primary
      phosphorylation sites are localized between amino acid residues 212-231 of the
      longest tau.
AB  - Alzheimer's disease (AD) is pathologically characterized by the appearance of
      neurofibrillary tangles (NFT), senile plaques, and loss of subpopulation of
      neuronal cells. The NFT is composed of paired helical filaments (PHT) with
      extensively modified protein T as its primary constituent. Previously we had
      reported on the hyperphosphorylation of T by a double-stranded-DNA-stimulated
      protein kinase (DNA-PK). In this communication, we have compared the DNA-PK
      mediated phosphorylation of native and truncated TS with that catalyzed by the
      cAMP-dependent protein kinase (PKA). In addition, we have attempted to map the
      primary site(s) of phosphorylation of T by DNA-PK. Our results suggest that DNA
      PK phosphorylates T at sites substantially different from those targeted by PKA.
      Furthermore, we show that the primary phosphorylation sites lie between amino
      acid residues 212-231 (using numbering system for the longest T, which is the
      isoform with four "repeats" and a 58 amino acid "insert" at the carboxyl- and
      amino-termini, respectively, of the protein molecule).

PMID- 8886267
TI  - Binding properties of human immunodeficiency virus type-2 (HIV-2) RNA
      corresponding to the packaging signal to its nucleocapsid protein.
AB  - The nucleocapsid (NC) protein of human immunodeficiency virus type-1 (HIV-1)
      contains two zinc finger motifs (ZFMs), and binds specifically to the packaging
      signal which is located in the 5' leader sequence of the viral genomic RNA
      between the first splice donor and the gag initiator codon (AUG). In this study,
      we analyzed the specificity of the binding of the corresponding region of HIV-2
      (Region 3) to its NC protein (NCp8), by performing a competitive ultraviolet (UV)
      cross-linking assay using in vitro-synthesized 32P-labeled and unlabeled RNAs
      corresponding to a sequence between the primer binding site and the gag AUG
      (Region 1). Binding of 32P-labeled Region 1 RNA to NCp8 was inhibited
      specifically by adding unlabeled Region 1 and 3 RNAs and no specific binding was
      detected using deletion mutant peptides of NCp8. These findings suggest that the
      region(s) which bind(s) specifically to HIV-2 NCp8 lie(s) between the first
      splice donor and the gag AUG in the 5' leader sequence and that NCp8 is the
      minimum binding region responsible for the specific binding of the region
      downstream of the first splice donor site of HIV-2 RNA.

PMID- 8886268
TI  - Identification of an AP-2 element in the -323 to -285 region of the TNF-alpha
      gene.
AB  - We have identified a region of the human TNF-alpha promoter between nucleotides 
      323 and -285, capable of influencing transcriptional activity. This region
      encompasses the -308 polymorphism and contains a 10 bp sequence homologous to the
      consensus binding site of activator protein-2 (AP-2). Protein complexes derived
      from U937 and Jurkat cells were found to bind to this element. Competitive EMSA
      using a consensus AP-2 oligonucleotide indicated that AP-2 may be involved.
      Functional assays demonstrate that this region can repress activity of a
      heterologous promoter in the Jurkat T-cell line, but act as an inducible enhancer
      of transcription in U937 cells.

PMID- 8886269
TI  - Beta 1 integrin subunit dimerization via disulfide bonds.
AB  - Integrins of the beta 1 family were isolated from human smooth muscle. SDS-PAGE
      analysis and subsequent immunoblotting demonstrated that integrin samples contain
      a protein immunologically related to beta 1 integrin subunit with the previously
      undescribed apparent molecular mass 205 kD. One-dimensional peptide mapping
      showed that the 205 kD protein is not a novel beta 1 related integrin subunit,
      but a beta 1 integrin subunit dimer. After reduction the major part of the beta 1
      immunoreactive material migrated from the 205 kD to 130 kD region, indicating
      that beta 1 integrin subunit dimers were formed via disulfide bonds. When
      electrophoretically pure beta 1 monomer and dimer forms were analized it was
      found that during SDS-PAGE about 30% of beta 1 integrin subunit monomers were
      organized into dimers while approximately 70% of the beta 1 dimer form was partly
      disrupted into monomers. It was suggested that this steady-state process is a
      result of a reversible reaction between intra- and intermolecular disulfide
      bonds. Possible in vivo dimerization of integrins via disulfide bonds is
      discussed.

PMID- 8886270
TI  - Enhancement by F-actin of MgATP-dependent dopamine uptake into isolated
      chromaffin granules.
AB  - Interaction of chromaffin granules with the microfilament network in the
      cytoplasmic space of adrenal medullary cells has been proposed, but the influence
      of chromaffin granule-microfilament interaction on granule function has not yet
      been studied. In the present study, the effect of F-actin on dopamine uptake into
      isolated chromaffin granules was examined. The MgATP-dependent component of
      dopamine uptake was significantly enhanced by F-actin. In contrast, catecholamine
      efflux from the granules was not significantly altered by F-actin under the
      conditions in which the enhancement of MgATP-dependent dopamine uptake was
      observed. These findings suggest that the interaction of chromaffin granules with
      the microfilament network results in the enhancement of MgATP-dependent dopamine
      uptake into the granules, thus modulating the accumulation and storage of
      catecholamines in the adrenal medullary cell.

PMID- 8886271
TI  - Transblot identification of avidin-interacting proteins in rat salivary glands.
AB  - Blotting of rat parotid gland proteins separated by SDS-PAGE and transferred to
      Immobilon transfer membranes revealed that avidin-peroxidase conjugate interacted
      with bands having estimated molecular weights of 72, 74, and 120 kDa. Even at the
      lowest concentration of avidin-peroxidase used in the general ABC method (1:2000
      dilution), three bands were clearly discernible. The staining reaction of parotid
      gland proteins was eliminated on preincubating the proteins with native avidin.
      The staining reaction was markedly reduced with the proteins obtained from
      submandibular/sublingual glands.

PMID- 8886272
TI  - Characterization of a novel nucleolytic activity of acylphosphatases.
AB  - A novel enzymatic activity on nucleic acids was discovered in both muscle type
      (MT) and erythrocyte or common type (CT) isoforms of acylphosphatase, an enzyme
      that was previously known as a hydrolase (E.C.3.6.1.7). Both deoxyribonucleic and
      ribonucleic hydrolitic activity were assayed on a variety of substrates. Our
      results demonstrate that acylphosphatase possesses both Mg++ dependent
      deoxyribonuclease and ribonuclease activities, at pH ranging from 5.0 to 6.8.
      Furthermore, we present evidences, for both isoenzymatic forms, of the
      coexistence of exonucleolytic and endonucleolytic activities on DNA.

PMID- 8886273
TI  - Purification and characterization of chromogranin-A from the adrenal gland of
      human and bovine.
AB  - In the present study, we report a simple, highly reproducible procedure for the
      purification of chromogranin A. A three step column chromatography of supernatant
      from human and bovine provided a major single band at M(r) 67 and two minor bands
      at low molecular mass. Identity of the major and minor bands of CgA was confirmed
      by western blotting using LK2H10, a monoclonal antibody against chromogranin A.
      Recognition of smaller fragments in the final preparation in both species by
      antibody to chromogranin A may suggest that these are the proteolytic breakdown
      product of the main protein. Bovine adrenal gland was found to be many fold
      richer in chromogranin than human adrenal gland. The simplification of the
      purification procedure for CgA may now help in elucidating further physiological
      function of this protein.

PMID- 8886274
TI  - Conformational change of cyclic AMP receptor protein by the binding of cyclic
      nucleotide.
AB  - The cAMP Receptor Protein (CRP) of Escherichia coli requires a conformational
      change induced by the binding of cAMP in order to function as a site-specific DNA
      binding protein. An intrinsic fluorescence study showed that the tryptophan
      residues at position 13 and 85 within CRP were located in an internal, nonpolar
      environment, and the conformational change induced by the binding of cAMP
      occurred around the tryptophan residue NMR experiment has manifested that the
      comformational change around the tryptophan residue at position 85 and histidine
      residue at position 159 of CRP is induced by the binding of cAMP. An extrinsic
      fluorescence study showed that the distance between the two cysteine 178 residues
      in the dimer was within about 3.5 A. This distance didn't exhibit a large change
      upon cAMP binding.

PMID- 8886275
TI  - Bisindolylmaleimide inhibits the PMA-induced down-regulation of collagen
      synthesis in fibroblasts.
AB  - We assessed the role of protein kinase C (PKC) in the regulation of collagen
      synthesis. Two PKC activators, Phorbol 12-myristate 13-acetate (PMA) and 1-oleyl
      2-acetyl-sn-glycerol (OAG), decreased the relative rate of collagen synthesis in
      a dose- and time-dependent manner in fibroblasts, whereas an inactive phorbol
      ester, 4 alpha-phorbol didecanoate failed to affect the collagen synthesis. In
      PKC-depleted cells both PMA and OAG were unable to inhibit collagen synthesis.
      Bisindolylmaleimide, a specific inhibitor of PKC, completely abrogated PMA
      induced inhibition of collagen synthesis in a dose-dependent fashion while two
      other PKC inhibitors with low specificity, H7 and staurosporin failed to block
      PMA effect on collagen synthesis. The results provide evidence that collagen
      synthesis is regulated through the signal pathway involving PKC activation.

PMID- 8886276
TI  - Characterization of natriuretic peptide receptors in the rat parotid.
AB  - Competition studies between 125I-ANP and ANP (atrial natriuretic peptide) or the
      ring-deleted analog C-ANF4-23 (C-ANF) revealed the presence of the A-type
      natriuretic peptide receptor (GC-A receptor) and the ANP-clearance (ANP-C)
      receptor in the rat parotid membrane. The ratio of the GC-A and ANP-C receptors
      was about 3 to 1. Enhancement of the cGMP level by the C-type natriuretic peptide
      (CNP) revealed the presence of the B-type natriuretic peptide receptor (GC-B
      receptor) in the rat parotid gland. Based on the binding studies with ANP and C
      ANF and cGMP analysis by ANP and CNP, the natriuretic peptide receptors in the
      rat parotid gland were demonstrated to have a rank order on the amount of GC-A
      receptor > GC-B receptor > ANP-C receptor.

PMID- 8886277
TI  - Identification and characterization of an RNA specific primer for human tumor
      necrosis factor receptor I (TNFR-I).
AB  - An RNA specific primer amplified TNFR-I cDNA from cellular RNA by single-tube
      (ST) RT-PCR without interfering with the presence of genomic DNA of cell was
      identified. The primer detected TNFR-I from 1 ng of cellular RNA by ST RT-PCR,
      and was not cross-reacted with TNFR-II despite of the homologous sequence between
      TNFR-I and -II. In addition, the mechanism of the RNA specificity of the primer
      was investigated. An intron of 0.43 kb was inserted in the 5'-925 of TNFR-I mRNA
      sequence. The result corresponded with the previous determination of TNFR-I gene
      structure. Thus, it appears that the RNA specificity of the primer might be
      resulted from the antisense primer hybridizing to exon-intron junction. Owing to
      its high sensitivity and specificity to TNFR-I RNA, the RNA specific primer may
      be potentially utilized for the determination of human TNFR-I gene expression by
      in situ RT-PCR.

PMID- 8886278
TI  - Proton pump and auxin effect in Arabidopsis thaliana leaves during the
      development.
AB  - The plasma membrane from Arabidopsis thaliana leaves (wild-type and F mutant) has
      been purified by two-phase partitioning and the H(+)-transport activity was
      tested in vitro in the presence of different concentrations of IAA. While 1
      microM of IAA had no effect, higher concentrations (10 microM and 100 microM)
      were inhibitory in 25 short days grown wild-type plants. However, the activity
      was increased by about 16% after 10 supplementary short days of growth (from 25
      to 35 SD) in the represence of 10 microM of IAA. No significant sensitivity to
      the tested concentrations of auxin was observed during the development in short
      days (30, 38, 42 SD) or even the plants were induced by a 24 h of continuous
      light. The variability was not observed for a given developmental stage, from one
      experiment to another, but it was also observed after light induction of F mutant
      plants.

PMID- 8886279
TI  - Guanidino compounds generate reactive oxygen species.
AB  - Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous
      substances in body tissues. Extremely high levels of these substances are known
      to be related to the pathogenesis of epilepsy and renal failure such as uremia.
      In this study it was demonstrated that methylguanidine, guanidinoacetic acid and
      guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous
      solution. These findings suggest that a high level of guanidino compounds
      accumulating near or within cells such as neurons (in an epileptogenic focus) or
      nephrons (in uremic patients) may cause free radical damage leading to these
      clinical disorders. Arginine may have a similar role in the pathogenesis of
      hyperarginemia.

PMID- 8886280
TI  - Mitochondrial NADH dehydrogenase activity and ability to tolerate acetaldehyde
      determine faster ethanol production in Saccharomyces cerevisiae.
AB  - In rapidly fermenting yeast, the rotenone insensitive mitochondrial NADH
      dehydrogenase was not completely repressed by high glucose. This activity
      appeared to enhance the glycolytic rate due to which acetaldehyde accumulated
      intracellularly. To overcome the toxicity of acetaldehyde, the strain produced
      stress proteins. During late stationary phase of growth, the accumulated
      acetaldehyde was converted to ethanol resulting in faster ethanol production.

PMID- 8886281
TI  - A novel DNA cleaving agent, 2,2'-bis(2-aminoethyl)-4,4'-bithiazole, induces
      thymocyte apoptosis.
AB  - The incubation of rat immature thymocytes with 2,2-bis(2-aminoethyl)-4,4'
      bithiazole, which possesses the cleaving activity toward plasmid DNA in the
      presence of Co2+, resulted in an increase in DNA fragmentation. No DNA
      fragmentation of the cells was induced by 2,2-bis(3-aminopropyl)-4,4'-bithiazole,
      which has little cleaving activity toward plasmid DNA. Analysis of fragmented DNA
      from thymocytes treated with 2,2-bis(2-aminoethyl)-4,4'-bithiazole by agarose gel
      electrophoresis revealed that the compound produced 50 kbp DNA fragments and
      caused internucleosomal DNA fragmentation. In addition, the confocal microscopic
      images of thymocytes treated with the compound showed condensation of chromatin.
      These results indicate that bithiazole derivative induces thymocyte apoptosis
      with the biochemical and morphological characteristics through triggering DNA
      scission.

PMID- 8886282
TI  - Redox regulation of signal transduction in smooth muscle cells: protein kinase C
      inhibition by thiol agents.
AB  - Thiol depleting agents phenylarsine oxide and N-ethylmaleimide significantly
      inhibited the phorbol ester induced protein kinase C activation in vascular
      smooth muscle cells. Phenylarsine oxide is a good protein tyrosine phosphatase
      inhibitor. Sodium orthovanadate, also a protein tyrosine phosphatase inhibitor,
      neither activated nor inhibited protein kinase C in vascular smooth muscle cells.
      Phenylarsine oxide, N-ethylmaleimide, orthovanadate, hydrogen peroxide and
      pervanadate [sodium orthovanadate + hydrogen peroxide] all significantly induced
      mitogen activated protein kinase in vascular smooth muscle cells. Phorbol ester
      and platelet derived growth factor induced mitogen activated protein kinase was
      inhibited by phenylarsine oxide pretreatment to vascular smooth muscle cells.
      However, hydrogen peroxide/pervanadate induced mitogen activated protein kinase
      was not prevented by phenylarsine oxide. These results suggest that oxidation of
      the cellular thiols inhibits the protein kinase C and activates mitogen activated
      protein kinase in vascular smooth muscle cells. In addition, peroxides induced,
      the activation of mitogen activated protein kinase in vascular smooth muscle
      cells which is independent of protein kinase C.

PMID- 8886283
TI  - Cellular and subcellular localization of glycogenin in chicken retina.
AB  - We investigated the cellular and subcellular localization of glycogenin in
      chicken retina using a polyclonal antibody raised against chicken muscle
      glycogenin. The antiserum recognized both free and glycogen-bound glycogenin on
      dot blots. Immunocytochemistry revealed an uniform staining of all the retina
      layers except for the outer segments and ganglion cells layers that were very
      weakly stained and for the inner segments layer and a zone between the inner
      nuclear and inner plexiform layers that were heavily stained. Electron microscopy
      of neuronal cells showed immunoreactivity localized in the cytoplasm and nucleus.
      This is the first description of the cellular and subcellular localization of
      glycogenin. Our results suggest that the biosynthesis of glycogen could begin in
      both, the cytoplasm and nucleus of the neurone.

PMID- 8886284
TI  - tRNA(Trp) as cofactor of gelonin, a ribosome-inactivating protein with RNA-N
      glycosidase activity. Features required for the cofactor activity.
AB  - Purified beef and rabbit liver tRNA(Trp), but not yeast tRNA(Trp), increase the
      in vitro inactivation of eukaryotic ribosomes by gelonin, a ribosome-inactivating
      protein with RNA-N-glycosidase activity on 28S rRNA. Aminoacylation and stepwise
      trimming of the 3'-end of bovine tRNA(Trp) affect the cofactor activity, the most
      active species being that shortened by the last two nucleotides. ATP only
      moderately increases the activity of purified mammalian tRNA(Trp) and in this
      increase the cognate aminoacyl-tRNA synthetase apparently has no role. Mobility
      shift experiments indicate that bovine tRNA(Trp) binds both to ribosomes and to
      gelonin and favours the dissociation of gelonin from ribosomes.

PMID- 8886285
TI  - Dopaquinone hydroxylation through topaquinone cofactor in copper amine oxidases:
      a simplified chemical model.
AB  - A simple model, 4-tert-butyl-1,2-benzoquinone, was chosen to study the
      hydroxylation step of the tyrosine-derived Dopaquinone residue at the active site
      of copper amine oxidases in the self-catalytic generation of the Topaquinone
      cofactor. This hydroxylation step was studied both in the presence and absence of
      free copper(II), and was found to be dependent on pH value but not on the
      presence of metal ions. It is therefore proposed that, hydroxide ion and not
      water should be the true reactive species in this key biosynthetic step of the
      Topaquinone cofactor, and that the active site Cu2+ is implied, at this point of
      cofactor biosynthesis, in the quinonisation of Topa rather than in the
      hydroxylation of Dopaquinone.

PMID- 8886286
TI  - Isolation and properties of anionic protease inhibitors from buckwheat seeds.
AB  - Three protease inhibitors (BWI-1, BWI-2 and BWI-4) from buckwheat seeds were
      purified to homogeneity and characterized. Their molecular masses were 7.7-9.2
      kDa according to gel-filtration and mass spectrometry. Amino acid analysis
      revealed a high content of glutamic acid and valine and a low content of
      isoleucine, aromatic and sulfur-containing amino acids. Data illustrating the
      temperature and the pH stability of the inhibitors are presented. Each of the
      inhibitors formed a inhibitor complex with trypsin in a molar ratio 1:1 and
      contained an Arg residue at the reactive site. In addition to trypsin, BWI-1 and
      BWI-2 inhibited chymotrypsin, however, less effectively. None of the isolated
      inhibitors suppressed activity of papain, leukocyte elastase, pepsin and
      subtilisin.

PMID- 8886287
TI  - Susceptibility of growth factors to degradation by Helicobacter pylori protease:
      effect of ebrotidine and sucralfate.
AB  - In this study, we investigated the susceptibility of the growth factors (EGF,
      bFGF, TGF beta and PDGF) to degradation by the protease elaborated by H. pylori
      and assessed the effect of antiulcer agents, ebrotidine and sucralfate, on this
      enzymatic action of the bacterium. The colonies of H. pylori were washed with
      saline, filtered to retain the bacteria, and the filtrate used as an enzyme
      source. The assays revealed that while EGF and beta FGF showed only marginal (5
      7%) susceptibility to H. pylori protease, a 61.7% degradation occurred with PDGF
      and 62.3% with TGF beta. Introduction of ebrotidine or sucralfate to the assay
      system led to the reduction in the rate of growth factors degradation, which at
      50 micrograms/ml ebrotidine reached the value of 85.1% for PDGF and 88.6% for TGF
      beta, while with sucralfate the optimal inhibition of PDGF (79.6%) and TGF beta
      (82.7%) degradation occurred at 200 micrograms/ml. The results demonstrate that
      PDGF and TGF beta are susceptible to H. pylori degradation and that antiulcer
      agents, ebrotidine and sucralfate are capable of counteracting this effect.

PMID- 8886288
TI  - Carbamazepine inhibits the potentiation by adenosine analogues of agonist induced
      inositolphosphate formation in hippocampal astrocyte cultures.
AB  - Carbamazepine (CBZ) resembles lithium in its beneficial effects in therapy and
      prophylaxis of affective disorders. Since lithium is presumed to act via an
      attenuation of the inositolphosphate/Ca(2+)-second messenger system, it is of
      particular interest whether or not CBZ might also have inhibitory effects on this
      type of signal transduction. CBZ is an antagonist of adenosine A1-receptor
      subtypes. We show here that activation of adenosine A1-receptors potentiates the
      phenylephrine induced formation of inositolphosphates in hippocampal astrocytes
      and that this potentiating effect is inhibited by CBZ at a therapeutically
      relevant concentration. These results indicate that CBZ can by antagonism of
      adenosine A1-receptors inhibit the inositolphosphate/Ca(2+)-signalling in neural
      pathways regulated by adenosine.

PMID- 8886289
TI  - Enhanced protein kinase C activity and translocation in bipolar affective
      disorder brains.
AB  - Protein kinase C (PKC) activity and its redistribution were determined in the
      frontal cortices of postmortem brains of bipolar affective disorder subjects and
      age-, sex-, and postmortem time-matched controls. Membrane and cytosolic PKC
      activity was determined by histone phosphorylation using [32P]-adenosine
      triphosphate as substrate. Specific PKC isozyme levels were assessed by Western
      blot analysis using antipeptide antibodies. Brain membrane-associated PKC
      activity was higher in bipolar vs. control tissue. An examination of the specific
      PKC isozymes in cortical homogenates revealed that cytosolic alpha- and membrane
      associated gamma- and zeta PKC isozymes were elevated in cortices of bipolar
      affective disorder subjects, whereas cytosolic epsilon PKC was found to be
      reduced. In control brain slices, incubation with 1 mumol/L phorbol 12-myristate
      13-acetate (PMA) caused an increase in membrane PKC activity, whereas cytosolic
      enzyme activity was decreased. This redistribution of the enzyme by PMA was
      markedly potentiated in brain slices of bipolar subjects. The results suggest
      that PKC-mediated phosphorylation is increased in brains of subjects with bipolar
      affective illness.

PMID- 8886290
TI  - Do glucocorticoids contribute to the abnormalities in serotonin transporter
      expression and function seen in depression? An animal model.
AB  - Adrenocorticosteroids and serotonergic neurons exert reciprocal regulatory
      actions, and both are abnormal in depression. We evaluated whether
      glucocorticoids influence the serotonin transporter in rat platelets and brain by
      infusing dexamethasone for 26 days, sufficient for replacement of the entire
      platelet population. Effectiveness was verified by measurement of plasma
      dexamethasone levels, adrenal atrophy, and growth inhibition. At the end of the
      infusion, we examined [3H]paroxetine binding to platelet, hippocampal, and
      cerebrocortical membranes, and [3H]serotonin uptake into platelets and
      synaptosomes. Dexamethasone slightly reduced platelet [3H]paroxetine binding
      (12%) and had no effect on binding in brain. Platelet [3H]serotonin uptake was
      unaffected, but synaptosomal uptake was significantly reduced. In neither
      platelets nor synaptosomes did dexamethasone alter imipramine's ability to
      inhibit uptake. Thus, elevated glucocorticoids are not responsible for reduced
      platelet serotonin transporter expression in depression, nor for resistance to
      imipramine's effect in platelets in elderly depression; however, reduced
      synaptosomal [3H]serotonin uptake indicates that glucocorticoids can affect
      transport efficiency, even when the number of transporter molecules is unaltered.

PMID- 8886291
TI  - MRI brain abnormalities in chronic schizophrenia: one process or more?
AB  - It has been suggested that schizophrenia is primarily a prefrontal-temporal
      limbic circuitry disorder. Further, it has been argued that primary neurologic
      vulnerability to the illness is established only during early stages of brain
      development and is not progressive. We tested the hypothesis of whether brain
      volume losses in prefrontal and temporal-limbic regions have occurred either
      before or after brain growth was hypothesized to be complete in schizophrenia.
      Nineteen chronic schizophrenic patients and 19 age- and sex-matched normal
      controls underwent magnetic resonance imaging (MRI). All scans were segmented
      into gray and white matter and cerebrospinal fluid (CSF) compartments for the
      frontal and temporal lobes and posterior cerebral hemispheres. Multivariate
      analysis of variance was used to analyze absolute intracranial cerebrum and
      subregion volumes, i.e., gray, white and CSF, absolute tissue (i.e., gray plus
      white) volumes, and tissue to intracranial volume (TCV) ratios. Patients showed
      significant intracranial volume reductions only in the frontal lobes but highly
      significantly lower TCV ratios (i.e., greater relative tissue loss) in all three
      major regions. It is suggested that the observed decreases in frontal
      intracranial volumes reflect a pathologic process in schizophrenia that impacted
      the frontal regions before brain growth was complete. We hypothesize that the
      generalized lower patient TCV ratios are attributable to a process that affected
      the whole cerebrum over a time period after brain volume had reached its maximum
      levels.

PMID- 8886292
TI  - Blink rate, neurocognitive impairments, and symptoms in schizophrenia.
AB  - This study addresses the relationship between blink rate (as a measure of central
      dopaminergic activity), symptoms, neuropsychological performance, as well as
      neurological signs in schizophrenia. Blink rate between schizophrenic patients
      and a matched control group was compared in both "relaxed" and "attentive"
      conditions. Blink rate was increased in schizophrenic patients in the "relaxed"
      condition but not in the "attentive" condition. The relationship between blink
      rate and clinical variables was examined in a larger sample of 204 patients. In
      both "relaxed" and "attentive" conditions, blink rate was related to
      "hallucinations," "anxiety," negative symptoms, and neuroleptic dosage. Attention
      was a significant predictor only in the "relaxed" condition. No other significant
      correlation was found between blink rate, neuropsychological impairments, and
      neurological signs. These findings suggest that blink rate is not related to
      neurocognitive impairments in schizophrenia.

PMID- 8886293
TI  - Acute effects of haloperidol on cerebral cortex blood flow in normal and
      schizophrenic subjects.
AB  - To evaluate the effects of neuroleptic medications on cerebral blood flow (CBF),
      cortical perfusion was quantified by the 133xenon technique in 8 unmedicated
      schizophrenics and 9 healthy controls before, and 1 and 3 hours after,
      administration of haloperidol (5 mg per os). At 3 hours, the normal subjects, but
      not schizophrenic patients, showed a significant increase in global mean
      perfusion (17 +/- 13%). Changes in CBF were not associated with plasma
      haloperidol levels or the presence of extrapyramidal side effects, and remained
      significant after controlling for pCO2. The lack of change in CBF in
      schizophrenic patients following acute haloperidol administration may be due to
      prior neuroleptic exposure, absence of anxiety, or other nonspecific factors, or
      may reflect a more fundamental feature of underlying pathophysiology in
      schizophrenia.

PMID- 8886294
TI  - Acute changes in cranial blood flow after cocaine hydrochloride.
AB  - Cerebral blood flow (CBF) was measured with the 133Xenon inhalation technique and
      forehead skin flow with laser Doppler, before and twice after 0.3
      milligram/kilogram of cocaine hydrochloride and a placebo given intravenously to
      six cocaine abusers, during two visits, separated by a minimum of one week. After
      cocaine, subjects showed significant increases in intoxication and tension.
      Systolic blood pressure and pulse rate also increased significantly after the
      drug but not after the placebo. CBF, with and without correction for end-tidal
      CO2, showed increases in left and right hemisphere after cocaine. The CBF
      increase was maximal in frontal, central and parietal regions. CBF changes
      correlated only with changes in a rated level of intoxication. Forehead skin flow
      did not change after cocaine or placebo. In habitual cocaine abusers, 0.3 mg/kg
      of cocaine, given intravenously produced increased CBF and no changes in forehead
      skin flow.

PMID- 8886295
TI  - P300 assessment of opiate and cocaine users: effects of detoxification and
      buprenorphine treatment.
AB  - We assessed cognitive function following heroin and cocaine detoxification and
      investigated whether buprenorphine treatment improves the disruptive effects of
      detoxification. Three groups of male volunteers meeting DSM-III-R criteria for
      concurrent opiate and cocaine dependence were tested using an auditory oddball
      paradigm before and after detoxification, and again on the 15th day of either
      buprenorphine or placebo treatment. There were no significant differences in P300
      amplitude, latency, or topographic distribution between drug-dependent subjects
      and controls on admission day. Following detoxification there was a significant
      decrease in P300 amplitude in the drug-dependent group at a time when self
      reported signs of withdrawal were minimal. Buprenorphine treatment significantly
      reversed the P300 amplitude decrement following detoxification, whereas placebo
      treated subjects continued to show depressed P300 amplitudes. These data
      demonstrate that buprenorphine treatment is effective in eliminating
      detoxification-induced impairments in one measure of cognitive ability.

PMID- 8886296
TI  - Prefrontal cortex dysfunction in Borna disease virus (BDV)--infected rats.
AB  - Viruses have been proposed to play a role in the pathogenesis of schizophrenia;
      however, the mechanisms by which infection could cause the affective, cognitive,
      and movement disorders of schizophrenia are not understood. The neurotropic RNA
      virus, Borna disease (BD) virus, linked to schizophrenia by serologic studies,
      causes movement and behavior disorders in a wide variety of mammalian and bird
      hosts. BD rats have hyperactivity and stereotyped behaviors similar to those that
      follow neurotoxic or electrolytic lesions in frontal cortex or its catecholamine
      afferents in rats. BD rats have high levels of viral nucleic acid in the
      prefrontal cortex (PFC), abnormal mesocortical dopamine activity (elevated levels
      of DOPAC in PFC), yet no alteration in specific binding of D1 or D2 receptor
      radioligands in PFC. Since frontal lobe dysfunction is frequently reported in
      schizophrenia, the BD rat model may provide insights into pathogenesis and
      management of this debilitating psychiatric disease.

PMID- 8886297
TI  - Unreliability of TRH test but not dexamethasone suppression test as a marker of
      depression in chronic vasculopathic patients.
AB  - Thirteen vasculopathic nondepressed men, admitted to the hospital 2 weeks earlier
      because of stroke, 10 age- and weight-matched patients with major depression, and
      10 age- and weight-matched normal controls were tested with TRH and on different
      occasion with the dexamethasone (DEX) suppression test (DST). Patients with
      stroke were tested again with TRH and DST after 1 year. All subjects were
      euthyroid. A blunted TSH response to TRH was observed in 77% of vasculopathic
      patients, 64% of depressed patients, and 27% of controls. Some depressed patients
      showed serum GH or cortisol increments in response to TRH. Nonsuppression to DEX
      was observed in 45% of depressed patients and 15% of vasculopathics but not in
      normal controls. These data indicate that, in contrast to cortisol nonsuppression
      to DEX, blunted TSH response to TRH has poor diagnostic value as a marker for
      depression after stroke and may merely represent the expression of neuroendocrine
      dysfunction associated with cerebral vasculopathy.

PMID- 8886298
TI  - Hippocampal neurons are damaged by caffeine-augmented electroshock seizures.
AB  - Caffeine-augmented electroconvulsive therapy has been introduced into medical
      practice without experimental confirmation that such seizure modification does
      not result in neuronal injury. In this report rats pretreated with caffeine prior
      to a series of nine electrically induced convulsions showed neuronal injury
      confined to hippocampal sectors and striatum. Electrically induced convulsions
      without caffeine pretreatment did not result in injury. The potential deleterious
      effects of caffeine augmentation of human electroconvulsive therapy require
      rigorous clinical assessment.

PMID- 8886299
TI  - Effect of acute tryptophan depletion on behavioral, cardiovascular, and hormonal
      sensitivity to cholecystokinin-tetrapeptide challenge in healthy volunteers.
AB  - Recent data suggest that serotonergic (5-HT) mechanisms may mediate the
      anxiogenic effects of cholecystokinin (CCK)-related peptides. Accordingly, we
      investigated the effect of lowering plasma tryptophan to the elicitation of
      behavioral, cardiovascular, and hormonal changes in healthy volunteers challenged
      with the tetrapeptide CCK agonist, CCK-4. Forty men without personal or family
      history of psychiatric disorders were randomly assigned to either a tryptophan
      free amino acid mixture, which decreases central 5-HT concentrations, or a
      control mixture. Five hours after administration of the amino acid mixture, all
      subjects received a single intravenous injection of CCK-4. The main finding of
      the study was that acute depletion of tryptophan failed to modify the panicogenic
      and cardiovascular effects of CCK-4, although it did enhance CCK-4-mediated
      increases in ACTH/cortisol and prolactin secretion. While these findings suggest
      that at least part of the neuroendocrine action of CCK-4 is mediated through the
      5-HT system, the locus of the 5-HT-CCK interaction and the specific 5-HT receptor
      subtype involved remains to be determined.

PMID- 8886300
TI  - Effect of age, sex steroids, brain region, and genetic strain on brain inositol
      monophosphatase activity.

PMID- 8886301
TI  - Relationship between DST nonsuppression and shortened REM latency in
      schizophrenia.

PMID- 8886302
TI  - Selective slow-wave sleep deprivation influences blood serotonin profiles and
      serum melatonin concentrations in healthy subjects.

PMID- 8886303
TI  - Are study dropouts different from completers?

PMID- 8886304
TI  - Fluvoxamine augmentation in clozapine-resistant schizophrenia: an open pilot
      study.

PMID- 8886305
TI  - The ten commandments of psychiatric research.

PMID- 8886306
TI  - Cerebrospinal fluid transmitter metabolites and atmospheric pressure.

PMID- 8886307
TI  - Glycine therapy of schizophrenia.

PMID- 8886308
TI  - Risks of cholesterol-lowering therapies.

PMID- 8886309
TI  - Nystatin affects zinc uptake in human fibroblasts.
AB  - The mechanism(s) by which zinc is transported into cells has not been identified.
      Since zinc uptake is inhibited by reducing the temperature, zinc uptake may
      depend on the movement of plasma membrane micoenvironments, such as endocytosis
      or potocytosis. We investigated the potential role of potocytosis in cellular
      zinc uptake by incubating normal and acrodermatitis enteropathica fibroblasts
      with nystatin, a sterol-binding drug previously shown to inhibit potocytosis.
      Zinc uptake was determined during initial rates of uptake (10 min) following
      incubation of the fibroblasts in 50 micrograms nystatin/mL or 0.1%
      dimethylsulfoxide for 10 min at 37 degrees C. The cells were then incubated with
      1 to 30 microM 65zinc. Michaelis-Menten kinetics were observed for zinc uptake.
      Nystatin inhibited zinc uptake in both the normal and AE fibroblasts. Reduced
      cellular uptake of zinc was associated with its internalization, not its external
      binding. In normal fibroblasts, nystatin significantly reduced the K(m) 56% and
      the Vmax 69%. In the AE fibroblasts, nystatin treatment significantly reduced the
      Vmax 59%, but did not significantly affect the K(m). The AE mutation alone
      affected the Vmax for cellular zinc uptake. The control AE fibroblasts exhibited
      a 40% reduction in Vmax compared to control normal fibroblasts. We conclude that
      nystatin exerts its effect on zinc uptake by reducing the velocity at which zinc
      traverses the cell membrane, possibly through potocytosis. Furthermore, the AE
      mutation also affects zinc transport by reducing zinc transport.

PMID- 8886310
TI  - Serum protein and zinc levels in patients with thoracic empyema.
AB  - The element Zn is the metal component or activator of many important enzymes. The
      tissue concentrations and activities of Zn metalloenzymes direct the rate of
      protein and nucleic acid syntheses, thereby influencing tissue growth and
      reperative processes. Most of the serum Zn is normally bound to circulating
      proteins. Low serum Zn concentrations might result from depletion of Zn-binding
      proteins. Serum protein and Zn concentrations have been reported to be depressed
      in patients with acute and chronic diseases. We compare the serum protein and Zn
      values of patients with thoracic empyema (n = 20) with those of a control group
      (n = 20). The values obtained in the empyema group were significantly lower than
      those in the control group before the study. Test group administered 220 mg zinc
      sulfate (ZnSO4.7H2O) over 20 d and there was a significant increase in the values
      for serum protein and Zn after the oral administration of the zinc sulfate.

PMID- 8886311
TI  - Minor and trace elemental determination in the Indian herbal and other medicinal
      preparations.
AB  - Medicinal plants described in the Indian "Ayurvedic" literature viz. Tulsi
      (Ocimum sanctum), Gulvel (Tinospora cardifolia), bitter Neem (Azadirachta
      indica), Kanher (Nerium Andicum), Vekhand (Acorus calamus), and Peacock's feather
      (ash) were analyzed for minor and trace elements by instrumental neutron
      activation analysis. The samples and the standards from the National Institute of
      Standards and Technology, USA and IAEA, Vienna were irradiated for 5 min, 1 h, 5
      h, and 10 h with thermal neutrons at a flux of 10(12)-10(13) n cm-2 s-1 in APSARA
      and CIRUS reactor at BARC, Bombay. High resolution gamma ray spectrometry was
      performed using a 45 cm3 HPGe detector and a 4096 MCA system. Concentrations of
      13 elements were determined. Zinc, manganese, and sodium were significantly
      higher in Tulsi leaves while zinc is higher in Neem leaves. Peacock's feathers
      were found to be rich in manganese, iron, copper, and zinc. A high concentration
      of mercury was also found in the peacock's feather ash. The therapeutic
      significance in restoring ionic balance is discussed.

PMID- 8886312
TI  - Apoptosis induced by selenium in human glioma cell lines.
AB  - Several studies have shown that selenium can inhibit tumorigenesis in tissues.
      However, little is known about the mechanism and the effect of selenium on DNA,
      especially in brain tumor cells. In this study we examined the biological effect
      of selenium on human glioma cell lines (A172 and T98G). Selenium exhibited an
      antiproliferative effect on these cell lines (and induced the typical ladder
      pattern of DNA fragmentation commonly found in apoptosis), which were prevented
      by catalase. Few effects of selenium on NT14 fibroblasts were found. These
      findings demonstrate that selenium may induce, by apoptosis, cell death of human
      glioma cell lines, which are resulting from free radical oxygen forming.

PMID- 8886313
TI  - Laboratory gloves as a source of trace element contamination.
AB  - Contamination in a trace element laboratory can come from a variety of sources,
      including laboratory gloves. Therefore, vinyl and latex gloves were obtained from
      as many manufacturers as would supply gloves. These gloves were either prepared
      for acid-washing and subsequent soaking in an acid solution, or immersed in an
      acid solution for a duration of either 1 min or 1 h. Incubation washes were
      analyzed for a variety of trace elements by flame atomic absorption spectroscopy
      (AAS) or inductively coupled mass spectrometry (ICP-MS). Results indicated that
      only three brands of vinyl gloves were acceptable for use in a trace element
      laboratory, whereas others had contamination of different elements. Latex gloves
      contained such high levels of biologically important elements that they were not
      considered suitable for routine trace element work. Vinyl gloves of choice should
      be routinely acid-washed before use in a trace element laboratory.

PMID- 8886314
TI  - Hypoglycemic effect of copper(II) acetate imidazole complexes.
AB  - The effect of copper(II) complexes on glucose metabolism was studied in normal
      and streptozotocin-induced diabetic rats. The copper(II) complexes used were
      bis(acetato)tetrakis(imidazole) copper (II), [Cu(OAc)2(Im)4], bis(acetato)bis(2
      methylimidazole) copper(II), [Cu(OAc)2(2mIm)2], bis(acetato)bis(1,2
      dimethylimidazole) copper(II), [Cu(OAc)2(1,2dmIm)2], and bis(acetato)bis(mu
      acetato)tetrakis(N-methylimidazole) copper(II) hexaaquo, [Cu2(OAc)4
      (NmIm)4].6H2O. Intramuscular administration of various doses of Cu(OAc)2(Im)4
      ranging from 10 to 100 mg/kg body mass to overnight fasted rats decreased blood
      glucose levels in a dose-dependent manner. Maximum hypoglycemic effect was
      observed 3 h after administration and lasted for at least 6 h. Treatment with 100
      mg/kg body mass of Cu(OAc)2(Im)4 caused hypoglycemic shock, which was
      irreversible and even lethal. Blood insulin levels were reduced sharply during
      this hypoglycemic shock. Similar changes in blood glucose level were achieved
      using Cu(OAc)2(2mIm)2. The same pattern of hypoglycemia, although less
      pronounced, was observed for Cu2(OAc)4(NmIm)4.6H2O and Cu(OAc)2(1,2dmIm)2. Binary
      copper(II) acetate complex, the ligand imidazole, and the inorganic form of
      copper, such as copper(II) chloride, had no significant effect on blood glucose
      level. These results indicate that the hypoglycemic activity of these complexes
      varies with the imidazole ligand and structure of the complex.

PMID- 8886315
TI  - Heroin dependence effects on some major and trace elements.
AB  - In this study, 56 (14 control and 42 addicts) adult human subjects of both sexes
      of different periods of heroin dependence were subjected to the measurement of
      whole blood, serum, and red blood cell levels of some trace elements (zinc,
      manganese, iron copper, and bromine), as well as some major elements (phosphorus,
      sulfur, calcium, potassium, and chlorine). This was done by the energy-dispersive
      X-ray fluorescence (EDXRF) technique, in which copper and bromine showed a
      significant rise in whole blood (male) (22 and 32%, respectively), while zinc,
      iron, manganese, calcium, sulfur phosphorus, potassium, and chlorine showed a
      significant drop (49, 8, 25, 34, 21, 51, 61, and 72%, respectively) in proportion
      to the period of heroin intake (6 yr) and in comparison with the control group.
      No significant sexual variation has been reported.

PMID- 8886316
TI  - Selenium status of healthy Turkish children.
AB  - Selenium concentrations, in blood plasma, red blood cells, hair of 61 healthy
      children, ages 0-14 yr, were determined using hydride generation atomic
      absorption spectrometry. Starting from late lactation period, selenium
      concentrations in all these matrices were found to be increasing with age. A good
      correlation was found between erythrocyte and plasma, hair and plasma, and hair
      and erythrocyte selenium concentrations. Although plasma, erythrocyte, and hair
      selenium concentrations of girls seemed to be higher than that of boys (only in
      erythrocytes), selenium concentrations of girls were found to be significantly (p
      < 0.002) higher than that of boys, 71 +/- 9 ng/mL, vs 65 +/- 10 ng/mL,
      respectively. Selenium status of Turkish children is found to be lower than that
      found in the literature; marginal selenium deficiency could be important in the
      development of some selenium deficiency related diseases. There is a need for
      extension of this study to healthy children from different regions in Turkey and
      to different disease states.

PMID- 8886317
TI  - Zinc deficiency and the desaturation of linoleic acid in rats force-fed fat-free
      diets.
AB  - Recent studies with rats force-fed zinc-deficient diets containing various types
      of fat failed to demonstrate a role of zinc in desaturation of linoleic acid. The
      present study was conducted to investigate the effect of zinc deficiency on
      desaturation of linoleic acid in rats that were initially force-fed fat-free
      diets to stimulate activity of desaturases. Therefore, rats were fed zinc
      adequate and zinc-deficient fat-free diets for 6 d. After that period, the groups
      were divided and half of the rats continued feeding the fat-free diet for another
      3.5 d whereas the other half was switched to a fat diet by supplementing the fat
      free diet with 5% safflower oil. In order to assess desaturation of linoleic
      acid, fatty acid compositions of liver phosphatidylcholine, -ethanolamine, and 
      serine were considered, particularly levels of individual (n-6) polyunsaturated
      fatty acids (PUFA). Levels of total and individual (n-6) PUFA were similar in
      zinc-adequate and zinc-deficient rats fed the fat-free diet throughout the
      experiment. Addition of 5% safflower oil increased levels of total and individual
      (n-6) PUFA in both zinc-adequate and zinc-deficient rats. However, total (n-6)
      PUFA in all types of phospholipids were higher in zinc-adequate rats than in zinc
      deficient rats. Additionally, in zinc-deficient rats there were changes of (n-6)
      PUFA levels typical for impaired delta 5 and delta 6 desaturation: linoleic acid
      and dihomo-gamma-linolenic acid were elevated; arachidonic acid, docosatetraenoic
      acid, and docosapentaenoic were lowered by zinc deficiency. Therefore, the study
      shows that zinc deficiency impairs desaturation of linoleic acid in rats force
      fed fat-free diets and therefore supports results from former convential zinc
      deficiency experiments suggesting a role of zinc for desaturation of linoleic
      acid.

PMID- 8886318
TI  - Nutrition status of the Chinese people.
AB  - Based on the available data collected with national nutritional survey, nutrition
      surveillance and the child surveys since 1987, analysis on food consumption,
      dietary pattern and nutrition status of the Chinese people has been done. The
      data sets used for the analysis are as follows. (1) 1987 Child Survey in 9
      Provinces-91,011 preschool children were sampled. (2) 1992 National Child Survey
      570,704 children under the age of 15 were sampled, with anthropometric
      measurement of 185,965 children under the age of 5. (3) 1990 Nutrition
      Surveillance-State Statistic Bureau (SSB) household survey in selected 7
      provinces (including Beijing Municipality) with 8629 household samples in the
      urban and 11,840 households in the rural covered 5341 children under the age of
      6, among which 1487 were in the urban and 3854 in the rural. (4) 1992 Third
      National Nutritional Survey-All the provinces and municipalities were covered
      with 25,033 household samples, among which 8474 were in the urban and 16,559 in
      the rural. 99,749 residents were surveyed, among which 30,723 were in the urban
      and 69,026 in the rural. Dietary survey data is used for comparison on food
      consumption and nutrient intake with 1990 nutrition surveillance data.

PMID- 8886319
TI  - A global view of food supply, access to food and nutrition adequacy.

PMID- 8886320
TI  - Current food and nutrition situation in south Asian and south-east Asian
      countries.
AB  - Food production in the countries of South and South-East Asia has shown a general
      upward trend during the last decade. Despite the considerable increase in
      population in many of these countries, food production per capita in 1988-90 was
      significantly higher as compared to 1979-81 figures, the increase being specially
      marked in such countries as Vietnam, Cambodia, Indonesia, and Malaysia. Available
      daily calorie supply was adequate to meet the requirement. The overall pattern of
      food production however has shown little change, with cereal production
      continuing to account for a predominant part of food production. There is no
      evidence of a significant uptrend with respect to production of pulses, milk,
      horticultural products, poultry or meat production in most countries. A unique
      and unfortunate feature of the nutrition situation in South-Asian countries is
      that the incidence of low birth weight deliveries is as high as 34% (1990),
      ranging from 25% in Sri Lanka to 50% in Bangladesh (as against less than 7% in
      the countries of Europe and North America). Even in countries of Africa where the
      overall food and nutrition situation is worse than in South Asia, the incidence
      is well below 20%. This is a reflection of the poor state of maternal nutrition
      in pregnancy. Florid nutritional deficiency diseases have shown a steep decline
      over the last two decades, but goitre and iron deficiency anaemia continue to be
      major public health problems, though some headway has been made with regard to
      the control of the former. Severe forms of growth retardation in children have
      declined but the majority suffer from mild and moderate forms of growth
      retardation. Countries of the Region are in varying stages of developmental
      transition. Among the burgeoning middle classes in some of these countries there
      are evidences of escalation of degenerative diseases such as diabetes and
      coronary heart disease. With increasing life expectancy, geriatric nutritional
      problems will demand increasing attention.

PMID- 8886321
TI  - Antioxidants in food and chronic degenerative diseases.
AB  - Both preventive and chain breaking antioxidants have a role in the limitation of
      free radical damage. Some of these may be regarded as "classical", like vitamins
      E and C but others are more recently discovered, such as the flavonoids,
      widespread in plant tissues, and the muscle constituents anserine and carnosine.
      The major conditions in which the role of antioxidants is under intense
      investigation include coronary artery disease, cancer and diabetes. There are
      theoretical underpinnings for the efficacy of antioxidants in each of these, with
      the protection of low density lipoprotein (in respect of the first) being
      exceptionally persuasive. Much attention is now being focussed on the flavonoids,
      which are surprisingly pleiotropic in their effects. For one of them, quercetin,
      over a dozen seemingly independent biological effects can be listed, including
      the inhibition of low density lipoprotein oxidation. Flavonoids also inhibit
      peroxidation in foodstuffs, as opposed to tissues. There is much controversy over
      antioxidant supplementation policies, some authorities recommending a massive
      programme of supplementation for all ages and classes, others stressing the value
      of the traditional mixed diet. This matter is unlikely to be resolved soon, but
      in the meantime sensible supplementation policies should be continued for those
      most vulnerable, that is, babies and the aged.

PMID- 8886322
TI  - Genetic variation and nutrition.
AB  - Advances in genetics and molecular biology indicate that susceptibility to
      chronic diseases such as coronary artery disease (CAD), hypertension, diabetes,
      obesity, osteoporosis, alcoholism, cancer, etc., to a great extent is genetically
      determined. Studies have shown that 50% of the variance in plasma cholesterol
      concentration is genetically determined, whereas 30%-60% of the variance in blood
      pressure is genetically determined. For fibrinogen, an independent risk factor
      for CAD, 15%-50% of the variance is genetically determined. In the U.K.
      population the variance for the fibrinogen level is 15% whereas in the Hawaiian
      population, the variance is 50%, indicating significant differences between
      populations. Among Australians, 75% of the variance in bone density is found to
      be genetically determined. Genetic variation influences the response to diet. For
      example, individuals with ApoE4 have higher cholesterol levels and a higher risk
      of CAD than those with ApoE3. Additional studies show that women of the ApoE 3/2
      phenotype stand to benefit the least from a high polyunsaturate: saturate (P:S)
      diet because of reduction in the more 'protective' high density lipoprotein
      cholesterol (HDL-C), whereas men of the ApoE 4/3 phenotype showed the greatest
      improvement in the LDL/HDL ratio. Therefore a general recommendation to increase
      the polyunsaturated content of the diet in order to decrease the risk for CAD is
      not appropriate for women with ApoE 3/2 phenotype. Thus, specific information is
      needed to define the optimal diet for an individual.

PMID- 8886323
TI  - Trace elements in health and diseases.
AB  - Remarkable progress has occurred in many branches of biology and health sciences
      during the last few decades. Trace element (TE) research has definitely shared in
      this explosion of scientific knowledge. Due to the improvements in analytical
      technology, the discovery of TEs in organism was realized. The developments of TE
      research have been promoted by the demand of public health (e.g. deficiency or
      toxicity). The profound knowledge of nutritional importance of TEs has been
      achieved with application of advanced methods in biological, medical and chemical
      fields, etc. In this paper, a new definition of essentiality of TEs is
      introduced. According to this definition, only ten TEs (Fe, Zn, F, Cu, I, Se, Mn,
      Mo, Cr, Co) are considered to be essential to humans. The others need more
      evidence to prove their essentiality in humans. The recent progress on the
      biochemical and immunological functions of TEs and on the roles of TEs in brain
      development are briefly described. The TEs, mainly Se, I, Zn, Fe, are more
      closely related to public health. Also, emphases are laid on balancing all
      nutrients when new knowledge of essential TEs is applied in public health.

PMID- 8886324
TI  - Soybean hull and its effect on atherosclerosis in non-human primates (Macaca
      fascicularis).
AB  - Twenty five monkeys were used in this experiment. They were divided into 5 groups
      with 5 animals as the replicates in each group and were adapted for two weeks to
      the environment before the data were collected. The animals were subjected to 5
      experimental diets, i.e. T1 (Basal diet); T2 (Basal diet + palm oil); T3 (Basal
      diet + palm oil + soybean hull); T4 (Basal diet + cholesterol) and T5 (Basal diet
      + cholesterol + soybean hull). The diets were given for a period of 8 months and
      water were given ad lib. Blood serum was taken before and during the experiment.
      The cholesterol, triglycerides, LDL and HDL were measured using the
      spectrophotometric method. At the end of the experiment thorax surgery was
      performed on the animals under general anesthesia. The aorta was removed
      surgically for histopathological observation stained with hematoxylin and eosine.
      The results showed that the soybean hull decreased the serum cholesterol level in
      the groups given palm oil (T2 vs T3) and the groups given cholesterol (T4 vs T5)
      i.e.: 163.4 vs 124.7 mg/dl and 359 vs 288.5 mg/dl respectively. The soybean hull
      did not significantly affect the serum triglyceride nor the LDL level when palm
      oil was given in the diet, but it significantly decreased the two parameters
      where cholesterol was given in the diet (102.5 vs 98.6 mg/dl triglyceride) and
      (231.9 vs 183 mg/dl LDL). The soybean hull did not seem to affect the HDL level.
      Histopathological observation of the aorta indicated that given T1, T2, T3, T4
      and T5 caused 45%, 41.67%, 31.25%, 86.25% and 53.38% lesion (Atheroma arteriale)
      respectively. It was concluded that the soybean hull given in the diet has the
      ability to prevent the development of atherosclerosis in the aorta of the
      experimental animals.

PMID- 8886325
TI  - Antioxidant status in persons with and without senile lens changes.
AB  - Biochemical evidence on lens culture suggests that antioxidant nutrients can
      protect lens against peroxidation caused by radiation. A case-control study was
      carried out on 262 middle aged (45-54) and aged (55-64) subjects. The
      relationship between biochemical markers of antioxidant status and senile lens
      changes (including cataract) was examined in 131 subjects with senile lens
      changes and 131 control subjects with clear lens. Antioxidant status was measured
      using plasma and erythrocyte glutathione peroxidase, erythrocyte superoxide
      dismutase and catalase activity and plasma levels of vitamin E and vitamin A.
      Subjects were grouped by age and sex. The results were as follows: (1) The
      subjects with lens changes tended to have lower plasma levels of vitamin E and
      vitamin A, lower activity of several antioxidant enzymes and higher level of MDA.
      (2) The subjects with senile lens changes had significantly lower erythrocyte
      glutathione peroxidase level. (3) In the middle-aged group, subjects with senile
      lens changes were observed to have lower erythrocyte and plasma glutathione
      peroxidase level than those without senile lens changes. The results suggest that
      appropriate amount of antioxidant nutrients might be expected to prevent or
      retard the process of lens changes.

PMID- 8886326
TI  - Status, prospect and policy of food development in China.

PMID- 8886327
TI  - Child malnutrition in China--present status and changing trend.
AB  - Halving the malnutrition of under five of years has been set as one of the goals
      to be achieved by the year of 2000 by Chinese government. So it is important to
      know the present status of child malnutrition and its trend of changing, in order
      to predict the possible outcome of the achievement of the goal. According to the
      Child Survey carried out by the State Statistic Bureau (SSB) in 26 provinces and
      autonomous regions and 3 municipalities in 1992, the prevalence of malnutrition
      of under five was: moderate and severe underweight, stunting and wasting were
      17.9%, 34.7% and 4.7% respectively. But there are significant differences among
      urban and rural children and between different provinces. The highest prevalence
      rate usually occurred in the second year of life of the children, and this may be
      the result of inadequate weaning food provided to the children. As compared with
      the data collected in 1987 by SSB in 9 provinces and autonomous regions, an
      impressive improvement in underweight has occurred within these 5 years. The
      average declined prevalence was 20.5%. It is specially true for urban children.
      To stunting, there was also improvement for urban children but not in the rural,
      resulting and over all increasing of prevalence by 5.9%. To wasting, the
      prevalence for urban children was low and remained at the same level while there
      was some what increase in the rural. So, according to these results, with
      constant economic development and more attempt made in areas and groups at risk,
      the goal to decrease malnutrition in half in terms of underweight could be
      reached by the year of 2000.

PMID- 8886328
TI  - Dietary control of lactase expression in the weaning rat.
AB  - The decline in lactase activity during weaning has been well established.
      However, its molecular mechanism remains to be explored. We studied changes in
      the expression of lactase in terms of the transcription and translation processes
      in rat microvillus membrane by Northern blot and Western blot analysis,
      respectively. To examine the effect of dietary change from a milk to a non-milk
      diet on the developmental pattern of lactase expression, weaning was prevented by
      keeping the rats under suckling conditions for 27 days after birth. This
      treatment only suppressed the extent of decline: while the weanlings showed 17
      percent activity compared to that of 4-day-old rats, the prolonged suckling rats
      showed only 42 percent. The changes in the expression of lactase mRNA and protein
      were parallel with the change of lactase activity. In other words, the
      fundamental pattern of significant depression of lactase expression occurred
      relatively independent of dietary modification. This observation indicates that
      the regulation of lactase expression is firmly determined at the transcriptional
      level, and that dietary factor such as the termination of lactose ingestion has
      only a relatively minor effect.

PMID- 8886329
TI  - Urinary creatinine-skeletal muscle mass method: a prediction equation based on
      computerized axial tomography.
AB  - A classic body composition method is estimation of total body skeletal muscle
      mass (SM, kg) from 24 h urinary creatinine excretion (Cr, g). Two types of
      prediction equations were suggested: one assumes a constant SM/Cr ratio; and the
      other assumes a highly variable SM/Cr ratio. We explored these two extreme
      possibilities by measuring SM with whole-body computerized axial tomography and
      collecting Cr during meat-free dietary conditions in 12 healthy young men.
      Prediction equations were developed in the men that fit these two equation types,
      SM = 21.8 x Cr (SD and CV of SM/Cr ratio, 1.3 kg and 6.0%, respectively) and SM =
      18.9 x Cr + 4.1 (r = 0.92, p = 2.55 x 10(-5), and SEE = 1.9 kg). The validity of
      each model is reviewed. This is the first investigation of Cr-SM method using
      modern techniques for quantifying total body SM mass.

PMID- 8886330
TI  - Possible role of the submandibular gland in the development of obesity in mice.
AB  - The possible role of submandibular glands (SMG) in the development of obesity was
      studied in two types of genetically obese mice, ob/ob and yellow Ay: Obesity is
      caused by hyperplasia followed by hypertrophy in ob/ob mice and mainly by
      hypertrophy in Ay mice. The histological features of SMGs exhibited clear sexual
      dimorphism in both mice similar to lean controls. The SMGs of ob/ob mice was
      smaller in size and had smaller granular convoluted tubular portions than lean
      controls, while the SMGs of Ay mice did not differ from lean controls.
      Sialoadenectomy before and after development of obesity generally reduced the
      gain of body weights in both sexes of Ay mice but not in ob/ob mice. The content
      of epidermal growth factor (EGF) in the SMGs was higher in Ay mice and lower in
      ob/ob mice than their controls. The possible role of EGF in the SMGs in the
      development of obesity is discussed.

PMID- 8886331
TI  - Dyslipidemia in urban Thais.
AB  - Serum lipid profiles were determined in 2,703 male and 792 female officials of
      the Electricity Generating Authority of Thailand (EGAT), aged 35-54 yrs, and 519
      Ramathibodi Hospital Staff (RHS) consisting of 66 men and 453 women, aged 19-61
      yrs. They are affluent-urban Thais. Mean serum total cholesterol (TC), low
      density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) levels in EGAT
      officials were higher than those in RHS with the same sex, whereas the opposite
      result was observed for their serum high density lipoprotein-cholesterol (HDL-C)
      levels. Men also showed higher serum TC, LDL-C, and TG but lower HDL-C levels
      than women. The major type of dyslipidemia in EGAT officials and RHS was
      hypercholesterolemia due to elevated serum LDL-C levels, but the elevated LDL-C
      level in RHS was less severe than that in EGAT officials. Besides, the prevalence
      of serum HDL-C level of 1.55 mmol/L, a negative risk factor for coronary heart
      disease, in RHS was higher than that in EGAT officials. The mean percentages of
      dietary fat-calories consumed by EGAT officials and RHS were 39% and 31%,
      respectively. Thus it is plausible that dietary fat intake influences their serum
      lipid levels. The beneficial effects of linoleate intake on serum lipoprotein
      profiles are illustrated in RHS.

PMID- 8886332
TI  - Influence of dietary fiber on the bioavailability of zinc in rats.
AB  - Young male albino rats were fed ad libitum semipurified diet supplemented with or
      without 5% of purified dietary fiber (cellulose, agar-agar, pectin, chitin or
      chitosan) for 31 days. Each test diet was carefully prepared in order to contain
      zinc at the level of 8 ppm from zinc acetate. In rats fed diets containing 5% of
      dietary fiber except chitosan, food consumption was higher than the control. The
      body weight gain of rats fed diets containing cellulose, pectin or chitin was
      higher than the control. However, food intake and body weight gain of rats fed
      the diet containing 5% of chitosan were definitely lower than not only the other
      fiber including diet groups but also the control group. When dietary fiber was
      added at 5% level to diet, zinc absorption was not changed to a considerable
      degree. But, the apparent zinc absorption of rats fed the agar-agar diet was 70%.
      On the other hand, zinc absorption in the pectin diet group was about 10% higher
      than the control. The total amount of zinc in tibia or femur of rats fed non
      fiber diets was a little higher than that of rats fed fiber diets.

PMID- 8886333
TI  - Proso millet protein elevates plasma level of high-density lipoprotein: a new
      food function of proso millet.
AB  - We examined the effects of dietary proso-millet protein on plasma levels of high
      density lipoprotein (HDL) cholesterol in different rats from animals reported in
      our previous studies. The results showed also, in this animal, that the ingestion
      of the millet protein elevates plasma levels of HDL-cholesterol like our earlier
      works. Taking into account the anti-atherogenic function of HDL, therefore, the
      millet protein would be useful as a new food ingredient which has the function
      that regulates cholesterol metabolism.

PMID- 8886334
TI  - Consumption pattern of carotene rich foods and development of a year calendar.
AB  - Consumption pattern of beta carotene rich foods from 500 households of Coimbatore
      district was elicited. Through market surveys in four seasons namely: summer,
      south-west monsoon, north-east monsoon and winter, a year calendar of beta
      carotene rich foods was developed. The total and beta carotene contents of five
      commonly consumed beta carotene rich foods both in raw and cooked states were
      determined. Results indicated that greens were mainly purchased from market and
      consumed 2-3 times per week. Cooking loss was maximum in boiling and minimum in
      shallow fat frying. Curry leaves (Murraya koenigii), amaranth tender (Amaranthus
      gangeticus), agathi (Sesbania grandiflora), and ponnanganni (Alternanthera
      sessilis) were the carotene rich foods available round the year. Cost of most
      greens was highest in summer and lowest in north-east monsoon. Within a cost of
      13-14 ps in summer, 4-10 ps in south-west monsoon and north-west monsoon and 4-12
      ps in winter season, the entire day's requirement of beta carotene (2400
      micrograms) could be obtained in the form of agathi/amaranth throughout the year:
      in the form of drumstick leaves and mint in south-west monsoon; as curry leaves
      and coriander leaves in winter and as agathi, paruppukeerai and amaranth in
      summer. From this year calendar, according to seasonal availability and cost, low
      cost high carotene foods can be selected and used for increasing the beta
      carotene intake in the intervention programmes and in the community.

PMID- 8886335
TI  - Time-lag effect of dietary fiber and fat intake ratio on Japanese colon cancer
      mortality.
AB  - The daily intake of total dietary fiber (TDF) was evaluated from data of the
      National Nutrition Survey (NNS) in Japan for 41 years since 1947. An
      interrelationship between the nutrient intake, including TDF, and the mortality
      from colon cancer in Japanese people was calculated by a simple correlation
      coefficient and time-series correlation coefficient. TDF intake per capita
      decreased rapidly from 27.4 g in 1947 to 15.8 g in 1963, and subsequently
      decreased by a lesser rate to 15.3 g in 1987. Fat intake increased rapidly from
      18.0 g in 1950 to 56.6 g in 1987. The age-adjusted mortality from colon cancer
      shows a significant positive correlation with both the intakes of animal protein
      and of total fat, and the fat energy ratio. A time-series analysis indicates that
      the mortality from colon cancer was negatively correlated with TDF with a 15-27
      year delay, the maximum correlation existing with a 23-year lag (r = -0.947). The
      TDF intake was less than 17.9 g in 1965. At the same time, the mortality from
      colon cancer increased rapidly. A fat/TDF ratio above 3.0 resulted in a rapid
      increase in colon cancer mortality. The non-adjusted mortality from colon cancer
      has much the same interrelationship with TDF and fat intake as the adjusted
      figures. It is suggested that the cause of the increased mortality from colon
      cancer in Japan is positively related to the increased intake of fat and protein.
      In addition, the decrease in TDF intake has accelerated the mortality of colon
      cancer after a delay of 23-24 years. The importance of fat/TDF as a nutritional
      criterion for the incidence of colon cancer needs to be better recognized.

PMID- 8886336
TI  - Serum levels of antioxidant vitamins in relation to coronary artery disease: a
      case control study of Koreans.
AB  - With the changes in trends of disease pattern from infectious to chronic
      degenerative disease, cardiovascular disease has been considered as the major
      cause of death in Korea. Numerous studies have been done on the antioxidant
      effects of some vitamins in the prevention of chronic illness, but not many in
      relation to the cardiovascular disease. Therefore, the relation between
      antioxidant vitamins, mainly alpha-tocopherol (alpha-T) and beta-carotene (beta
      C), and coronary artery disease (CAD) such as angina pectoris and myocardial
      infarction has been investigated in this study. The blood samples were obtained
      from the CAD patients who were angiographically diagnosed within a month (100
      case group). Patients who had an experience of PTCA or CABG were excluded from
      the study. Control subjects were healthy adults who had normal EKG values, no
      chest pain and no past history of cardiac disease (100 control group). All
      subjects were free for serum lipid lowering drugs. Serum alpha-T and beta-C were
      analysed using HPLC. In addition to antioxidant vitamins, serum lipids (total
      cholesterol, HDL, TG) were also measured. Each case and control was matched in
      terms of age and sex. And all the CAD risk factors such as blood pressure,
      smoking, alcohol, serum lipid profile and BMI were adjusted to determine pure
      effect(s) of alpha-T and beta-C on the CAD. The concentrations of both alpha-T
      and beta-C were significantly lower in the CAD group than those in control group
      (P < 0.05); in CAD group, mean values of alpha-T and beta-C were 11.9 +/- 7.2
      (micrograms/ml), 35.8 +/- 3.1 (micrograms/dl) respectively. As for the levels of
      beta-C, it shows inverse relation with age, but not for the alpha-T levels. Serum
      levels of both vitamins did not show any significant differences in terms of sex,
      but men have a tendency o higher levels of beta-C, but lower levels of alpha-T.

PMID- 8886337
TI  - Iodization of village water supply in the control of endemic iodine deficiency in
      rural Sarawak, Malaysia.
AB  - A simple water iodizing system, which incorporates the Venturi principle in
      combination with the controlled release mechanism of a silicone-sodium iodide
      elastomer, for the iodization of rural piped-water supply in the control of
      endemic iodine deficiency has been developed and its effectiveness evaluated in
      three Iban longhouse villages in the iodine-deficient district of Lubok Antu,
      Sarawak. Urines were collected for iodine assays from women aged 15-40 years
      before and at 6 and 12 months after the connection of the iodinating device;
      goiter assessment was performed on the women at the start and end of the 1-year
      study. Water samples were collected for iodine assays at 2-weekly intervals. In
      all three villages, significant and sustained increases in median urinary iodine
      excretions, reaching levels recommended for an iodine-sufficient population, were
      observed; goitre prevalences were reduced in all the villages (by 22.6% to
      35.8%). The iodine levels in the water ranged from 34 micrograms/l to 212
      micrograms/L. In the control village, median urinary iodine excretions remained
      essentially unchanged but a small increase in goiter prevalence was observed. The
      iodized water was well received by the villagers and no adverse effects of water
      iodization were observed. The system functioned unattended throughout the one
      year period. The cost of providing supplemental iodine via the iodizing device is
      approximately 60 cents (U.S.) per family per year which is affordable by either
      the Government or the villagers. It is concluded that the iodizing system offers
      a new cost-effective strategy for the control of endemic iodine deficiency in
      Sarawak and may have applications in other areas with similar water sources.

PMID- 8886338
TI  - Rice bran oil and human health.
AB  - The available data in humans suggest that rice bran oil (RBO) is an edible oil of
      preference for improving plasma lipid and lipoprotein profiles similar to more
      commonly used vegetable oils. The observation that blending RBO with safflower
      oil at a specific proportion magnifies the hypocholesterolemic efficacy is of
      particular interest with regard to utilization of this oil. The occurrence of
      peculiar components such as gamma-oryzanol and tocotrienols in RBO might be
      responsible for its hypocholesterolemic effect.

PMID- 8886339
TI  - The effect of a chocolate bar supplementation on moderate exercise recovery of
      recreational runners.
AB  - To study the effects of a chocolate bar supplementation before exercise on
      improving recovery of physiological and metabolic changes induced by exercise, 16
      male students aged 18-20 years voluntarily served as subjects. A crossover design
      was employed. Each subject took part in two trials and ran an hour on a treadmill
      with the intensity of keeping heart rate at 148-150 min for each trial. Results
      showed that plasma glucose levels of subjects increased significantly (5.42 +/-
      0.83 mmol/L) at 15 min after ingestion of a chocolate bar and maintained in
      moderate high levels (4.92 +/- 0.57 mmol/L) until 30 min after an hour's running
      while the glucose levels were low and dropped to under normal ranges (3.84 +/-
      0.31 mmol/L) at 30 min after exercise as they were with a supplement of placebo.
      Results of plasma FFA, blood lactate and plasma urea nitrogen levels and RPE all
      indicated that chocolate bar supplementation before exercise benefits to create
      the necessary prerequisite for exercise and recovery.

PMID- 8886340
TI  - Nutritional status in chronic hemodialysis patients.
AB  - Hitherto, there has been no systematic evaluation of the nutritional status of HD
      patients in Thailand. 27 patients awaiting renal transplantation, 19 M 8 F, age
      47.2 +/- 8.6 y (mean +/- SD), underwent HD at Ramathibodi Hospital. Dietary
      assessment revealed the average daily intake of men and women to be respectively
      1571 +/- 314 and 1379 +/- 403 kcal, 47 +/- 11 and 42 +/- 14 g protein.
      Anthropometric data showed that mean of BMI, percent ideal body weight (%IBW),
      percent standard triceps skinfold thickness (%TSF) and percent arm muscle
      circumference (%std MUAMC) to be 20.5 +/- 2.6 kg/m2, 90 +/- 12, 75 +/- 30 and 100
      +/- 13, respectively. However, 37%, 56% and 70% of these patients had BMI, BW and
      MUAC less than the minimal cut-off levels. These data reflect the importance of
      energy depletion in these patients. The average serum albumin was 39 +/- 6 g/L
      while 52% suffered from low albumin levels. TC, LDL-C, HDL-C and TG were 4.34 +/-
      1.34, 2.9 +/- 1.06, 0.89 +/- 0.33 and 1.10 +/- 0.67 mmol/L while 15% had high TC,
      LDL-C and 58% had low HDL-C levels. Only one patient was suffered from
      hypertriglyceridemia. Whereas inadequate thiamine, riboflavin, ascorbic acid and
      alpha-tocopherol status were present in 4-30%, toxic levels of serum retinol were
      seen in almost all patients. Low serum zinc and copper levels were also present.
      This study disclosed a wide spectrum of nutritional problems usually overlooked
      in CRF patients undergoing chronic hemodialysis. Whereas zinc supplementation may
      be needed, vitamin A supplementation in these patients should be discouraged.

PMID- 8886341
TI  - Fish meal lecithin as alternative precursor of docosahexaenoate and choline.
AB  - Choline and docosahexaenoate (DHA) are essential nutrients for maintaining normal
      brain function. However, their existence in fish lecithin is ignored and excluded
      during the degumming step of conventional fish oil manufacturing process. The
      study aims to introduce fish lecithin as alternative precursor of choline and
      omega-3 fatty acids especially DHA for nutritional supplements. Four grades of
      Thai fish meals with protein contents ranging from 60-70% were used. Their lipid
      characteristics were examined. Fish meal's fats and lecithin were 9-15 and 2-3
      g/100 g, respectively. Total fatty acids constitute 23-27% monoenes without
      erucic acid and 24-28% polyenes including 15-19% DHA. Lecithin with 50% purity
      was prepared from grade-1 fish meal by means of consecutive methanol/n
      hexane/acetone extraction. The obtained lecithin contains choline upto 66-70
      mole% with DHA reaches to 20-23%. Its peroxide value of 57 and acid value of 9
      are accepted for food grade lecithin preparation, however, the further refinery
      process is still suggested. Since the world consumption of nutritional supplement
      foods is increasing steadily, the results of our study implies that fish lecithin
      is probably a promising source of choline and omega-3 fatty acids especially DHA
      for such an objective.

PMID- 8886342
TI  - Risk factors for cardiovascular disease in obese and normal school children:
      association of insulin with other cardiovascular risk factors.
AB  - OBJECTIVE: To investigate the level of insulin and other known cardiovascular
      risk factors in school children and their association with obesity. DESIGN: Cross
      sectional study. SUBJECTS: 123 normal and 116 obese school children categorized
      by weight-for-height, mean age: 10.2 and 10.5 years old respectively.
      MEASUREMENTS: Family histories of diseases by questionnaires; blood pressure (BP)
      and waist and hip circumferences by measurements; fasting blood for glucose,
      insulin, total cholesterol, HDL-cholesterol and triglycerides. RESULTS: The
      numbers of boys in the normal and obese group were 65 and 58, those of the girls,
      53 and 63 respectively. The obese group was more likely to have family histories
      of obesity, high blood pressure and diabetes; had significantly greater waist-hip
      ratio (WHR), higher systolic and diastolic BP, lower HDL-cholesterol, higher
      triglyceride and fasting insulin levels (with fasting blood sugar in the normal
      range) than the normal weight group. In a crude analysis, insulin levels were
      positively correlated with obesity, systolic BP, WHR, age and triglycerides and
      negatively associated with male gender and HDL-cholesterol. After adjustment
      using multiple regression, only obesity status, age, gender and triglycerides
      still remained significantly associated with insulin level. Limitation of
      utilizing family disease history report for identification of children at risk
      was discussed. CONCLUSION: These findings suggest that risk to coronary heart
      disease and hypertension through insulin resistance already operates in school
      aged children.

PMID- 8886343
TI  - Nutrition programs through public health centers in Korea.
AB  - In the period of confusion after the Korean War, there was an absolute shortage
      in the volume of food. The intake of energy and all other nutrients fell short of
      the recommended dietary intake. To solve the food shortage, there were many food
      assistant programs through the government channel. With the economic developments
      during past years, now, there are enough foods for everyone. Thus, food assistant
      program, which has been the only nutrition program in the government, is no
      longer needed except for low-income families. Currently, there are not enough
      nutrition programs in the government. In 1994, about 30 public health center
      start nutrition programs with the help of Korean Dietetic Association. In this
      study, kinds of nutrition programs, age, sex and number of participants, the
      content of programs are studied. The effects of nutrition programs are partially
      evaluated. Also, problems with current nutrition programs are discussed. Finally,
      future directions of nutrition programs in the public health centers are
      discussed.

PMID- 8886344
TI  - Nutri-action analysis as a research strategy to improve nutrition information,
      education and communication interventions in Asia.
AB  - What is lacking in nutrition information, education and communication (IEC) work
      today is accurate knowledge about the processes which bring about beneficial
      nutritional behavior changes. In this paper, Nutri-action Analysis is proposed as
      a mechanism for nutrition planners to gain this knowledge and seek ways to
      improve the effectiveness of nutrition IEC interventions. It suggests that a more
      holistic and dynamic approach is necessary to conceptualize nutrition IEC and
      increase its effectiveness in bringing about changes in behaviors which lead to
      nutritional status improvement. Nutri-Action Analysis, as a research strategy, is
      illustrated by a three-stage procedure: (i) pre-action, (ii) action, and (iii)
      post-action. This process leads investigators to begin conducting a macro
      analysis of nutrition IEC in general and within their specific contexts in order
      to understand the system and identify the best approach to be adopted for a
      nutrition IEC intervention in their particular context. What is discovered should
      then be tested in a community-based operational research study using both
      quantitative and qualitative data so that it is possible to subsequently conduct
      a synthesis focusing on process determinants.

PMID- 8886346
TI  - The role of vitamin A in iron deficiency anemia and implications for
      interventions.

PMID- 8886345
TI  - Arginine: new and exciting developments for an "old" amino acid.
AB  - Arginine (2-amino-5-guanidino pentanoic acid) was shown in 1895 by Hedin to be
      present in the proteins of horn. Metabolic nitrogen balance studies, conducted in
      1957 by Rose in human adults and in 1959 by Snyderman and coworkers in young
      infants revealed that a dietary source of this amino acid was not an obligatory
      requirement for growth and maintenance of nitrogen homeostasis in healthy
      individuals. Hence, it was initially classified as a non-essential (dispensable)
      amino acid and, perhaps, for reasons of this classification arginine did not
      receive the earlier attention it now deserves, in relation to an understanding of
      the nutritional biochemistry and physiology of its metabolism in humans subjects.
      However, there is currently a considerable interest in the cellular and tissue
      functions, as well as clinical, therapeutic significance, of arginine. In this
      paper we review the multiple functions of arginine, including its role in the L
      arginine-nitric oxide pathway, cellular regeneration, immune function, protein
      synthesis and protein breakdown. We then consider some in vivo aspects of the
      physiology of arginine metabolism, which varies greatly among eukaryotes, with
      particular reference to humans. Against this background, studies of arginine in
      the nutrition of humans under various pathophysiological conditions are reviewed
      briefly. Finally, a new, updated concept for the metabolic basis for the
      "conditional essentiality" of arginine is proposed.

PMID- 8886347
TI  - The effects of high energy and micronutrient supplementation on iron status in
      nutritionally at risk infants.
AB  - The study assessed the effects of supplementary feeding over 180 consecutive days
      on iron status of infants and toddlers at six tea plantation in West Java,
      Indonesia. The design used was a clinical trial: two eohorts (i.e., 12 and 18
      months old children) and three treatment groups (i.e., energy + micronutrient,
      micronutrient alone, and placebo) per cohort. Every day except Sunday, the
      infants attended day-care centers. Twenty four centers and 136 infants were
      selected. The infants were screened for weight and length and those meeting the
      criteria (i.e., < -1 SD of length-for-age, and between -1 and -2 SD of weight-for
      length of the NCHS reference) were included. The experimental unit was the day
      care centers (DCC), where each DCC was randomly assigned to one of the three
      treatment. As expected, groups of energy + micronutrient and micronutrient alone
      of the 12 months cohort experienced a significant upward shift in hemoglobin,
      ferritin and TS and a downward change in FEP, while the values for the group of
      placebo remain about the same as at base line. In the first 6 month of
      treatments, the ANOVA for each iron indicator yielded significant main effects of
      treatment (P < 0.01) and for Hb with (P = 0.059) on 12 months cohort. On the
      other hand, the main effects of treatment on hemoglobin, TS, ferritin and FEP
      were not significant for the 18 months cohort. In the second 6 months of
      treatments, the only significant of the treatment effect (P < 0.01) was in serum
      ferritin on 18-month cohort. Under these circumstances, energy has a positive
      role in improving iron stores. It is likely that the equilibrium of hemoglobin
      and each iron indicators were reached in 6 months of treatment except ferritin
      still continued to increase up to 12 month. The effects of treatment on the
      improvement of iron status was stronger in 12 months than in 18 months.

PMID- 8886348
TI  - The effectiveness of weekly iron supplementation regimen in improving the iron
      status of Chinese children and pregnant women.
AB  - It is evident that intermittent iron supplementation is better than daily
      supplementation in two aspects: iron absorption is more efficient and has
      insignificant side effects in contrast to the daily dose. The significantly
      higher daily iron loss observed in the daily iron supplemented groups rats also
      suggests alterations in total body iron metabolism. Based on serum ferritin
      distribution patterns, intermittent iron supplementation avoids temporary iron
      overload with daily iron supplemented. We conclude that weekly iron
      supplementation scheme is safer and easier to administer. This feasible strategy
      for the control of iron deficient anemia in pregnant women and children would be
      an effective iron-supplementation program (Baily et al., 1993).

PMID- 8886349
TI  - Interactions among micronutrient deficiencies and undernutrition in the
      Philippines.
AB  - Data gathered from the 1987 National Nutrition Survey in the Philippines provided
      the opportunity to study the interactions among micronutrient deficiencies and
      undernutrition in different age groups as basis for program targeting. A randomly
      selected set of 50% of the households (3,200) covered by the national survey
      served as source of subjects. Results showed that there was a greater proportion
      of anemia among the undernourished (as judged by weight for age in children and
      weight for height in adults) (66.0%) than among the adequately nourished (54.6%)
      (P < 0.01). However, the observed differences in the proportion of serum vitamin
      A deficiency and of goiter among the undernourished compared to the adequately
      nourished were not significant. Also not significant were the observed higher
      prevalence of anemia among subjects with acceptable serum vitamin A levels for
      both adequately nourished and undernourished, and the higher prevalence of
      vitamin A deficiency among the non-anemics. Again there were no significant
      differences in the prevalence of anemia among goitrous and non-goitrous subjects,
      as well as the prevalence of goiter among anemic and non-anemic subjects. Neither
      were there significant differences in the prevalence of vitamin A deficiency
      among goitrous and non-goitrous subjects, but there were significant differences
      in the prevalence of goiter among vitamin A deficient and non-vitamin A deficient
      subjects among the 7-14 years old and among pregnant and lactating women. The
      study concludes that at the national level, there is apparently an interaction
      between anemia and protein-energy undernutrition and possibly also between goiter
      and vitamin A deficiency in the high-risk age groups, but between anemia on the
      one hand and goiter and vitamin A deficiency in the other, perhaps because of
      clustering in the latter conditions not found in anemia and general
      undernutrition. These findings may be useful in targeting communities with high
      prevalence of micronutrient deficiencies by using prevalence of underweight and
      goiter as indicators for high prevalence of anemia and vitamin A deficiency,
      respectively.

PMID- 8886350
TI  - Behavior and physiology of the macaque vestibulo-ocular reflex response to sudden
      off-axis rotation: computing eye translation.
AB  - The vestibulo-ocular reflex (VOR) has historically been considered a
      computationally simple reflex: to stabilize images on the retina against imposed
      head rotation, the eyes must be counterrotated by an equal amount in the opposite
      direction. During almost any head rotation, however, the eyes are also
      translated. We show that the VOR compensates for 90% of this translation, and
      suggest a computational scheme by which this is done, based on a temporal
      dissection of the VOR response to sudden head rotation. An initial response that
      corrects only for imposed rotation is refined by a series of three temporally
      delayed corrections of increasing complexity. The first correction takes only
      head rotation and viewing distance into account; the second, head rotation,
      viewing distance, and otolith translation; and the third, head rotation, viewing
      distance, otolith translation, and translation of the eyes relative to the
      otoliths. Responses of type I gaze velocity Purkinje (GVP) cells in the
      cerebellar flocculus and ventral paraflocculus of rhesus monkeys were recorded
      during sudden head rotation. We show that cell discharge was modulated both by
      axis location and by viewing distance, suggesting that GVP cells play a role in
      the VOR response to rotation-induced eye translation.

PMID- 8886351
TI  - Vestibulo-ocular reflex of the squirrel monkey during eccentric rotation with
      centripetal acceleration along the naso-occipital axis.
AB  - The vestibulo-ocular reflexes (VOR) are determined not only by angular
      acceleration, but also by the presence of gravity and linear acceleration. This
      phenomenon was studied by measuring three-dimensional nystagmic eye movements,
      with implanted search coils, in four male squirrel monkeys. Monkeys were rotated
      in the dark at 200 degrees/s, centrally or 79 cm off-axis, with the axis of
      rotation always aligned with gravity and the spinal axis of the upright monkeys.
      The monkey's position relative to the centripetal acceleration (facing center or
      back to center) had a dramatic influence on the VOR. These studies show that a
      torsional response was always elicited that acted to shift the axis of eye
      rotation toward alignment with gravito-inertial force. On the other hand, a slow
      phase downward vertical response usually existed, which shifted the axis of eye
      rotation away from the gravito-inertial force. These findings were consistent
      across all monkeys. In another set of tests, the same monkeys were rapidly tilted
      about their interaural (pitch) axis. Tilt orientations of 45 degrees and 90
      degrees were maintained for 1 min. Other than a compensatory angular VOR during
      the rotation, no consistent eye velocity response was ever observed during or
      following the tilt. The absence of any response following tilt proves that the
      observed torsional and vertical responses were not a positional nystagmus. Model
      simulations qualitatively predict all components of these eccentric rotation and
      tilt responses. These simulations support the conclusion that the VOR during
      eccentric rotation may consist of two components: a linear VOR and a rotational
      VOR. The model predicts a slow phase downward, vertical, linear VOR during
      eccentric rotation even though there was never a change in the force aligned with
      monkey's spinal (Z) axis. The model also predicts the torsional components of the
      response that shift the rotation axis of the angular VOR toward alignment with
      gravito-inertial force.

PMID- 8886352
TI  - Transaural linear vestibulo-ocular reflexes from a single utricle.
AB  - To clarify the directional sensitivity of a single utricle with respect to the
      transaural linear vestibulo-ocular reflex (L-VOR) we studied seven patients
      before and after vestibular neurectomy. Patients were seated upright in an
      electrically powered car running on a linear track. Transaural acceleration steps
      of 0.24 g were applied randomly to the left and right in the dark. The slow phase
      velocity of the L-VOR was measured from the average of the induced compensatory
      eye movements. L-VOR asymmetry was calculated as (R-L/R + L x 100) and is < 13%
      in normals. Before surgery, responses were mostly symmetrical. One week after
      surgery, however, all patients had diminished or absent responses with medial
      acceleration of the remaining utricle. Asymmetries averaged 65% after correction
      for spontaneous nystagmus. Our findings indicate that afferents for the L-VOR
      originate from the lateral region of the macula where hair cells with ipsilateral
      on-directions are located.

PMID- 8886353
TI  - Three-dimensional orientation of the eye rotation axis during the Purkinje
      sensation.
AB  - The otolith-semicircular canal interaction during postrotatory nystagmus was
      studied in six normal human subjects by applying fast, short-lasting, passive
      head and body tilts (90 degrees in the roll or pitch plane) 2 s after sudden stop
      from a constant velocity rotation (100 degrees/s) about the earth-vertical axis
      in yaw. Eye movements were measured with 3-D magnetic search coils. Following the
      head tilt, activity in the semicircular canal primary afferents continues to
      reflect the postrotatory angular velocity vector in head-centered coordinates,
      whereas otolith primary afferents signal a different orientation of the head
      relative to gravity. Pitch (roll) tilts away from upright during postrotatory
      nystagmus after yaw rotation elicited a transient vertical (torsional) VOR.
      Despite the change in head orientation relative to gravity, postrotatory eye
      velocity decayed closely along the axis of semicircular canal stimulation
      (horizontal in head coordinates). These results suggest that postrotary nystagmus
      is largely organized in head-centered rather than gravity-centered coordinates in
      humans as suggested by the Purkinje-sensation.

PMID- 8886354
TI  - Saccular impact on ocular torsion.
AB  - When someone is tilted laterally, the shear force on the maculae of the utriculus
      and the sacculus is described by the sine and the cosine of the angle of tilt,
      respectively. So both the sacculus and the utriculus are stimulated, but in the
      literature, ocular torsion is normally attributed to utricular function alone
      (and, thus, seen as a response to y-axis linear acceleration). However, on the
      base of a series of experiments on a tilt chair, a linear track, human
      centrifuges, and during parabolic flights, we conclude that the sacculus
      contributes to ocular torsion as well (there is a response to z-axis linear
      acceleration). The data suggest that the ratio of the utricular and saccular
      impact on ocular torsion is 3:1. The utriculus generates conjugate and the
      sacculus disjunctive torsional eye movements.

PMID- 8886355
TI  - Ocular torsion before and after 1 hour centrifugation.
AB  - To assess a possible otolith contribution to effects observed following prolonged
      exposure to hypergravity, we used video oculography to measure ocular torsion
      during static and dynamic conditions of lateral body tilt (roll) before and after
      1 h of centrifugation with a Gx-load of 3 G. Static tilt (from 0 to 57 degrees to
      either side) showed a 10% decrease in otolith-induced ocular torsion after
      centrifugation. This implies a reduced gain of the otolith function. The dynamic
      condition consisted of sinusoidal body roll (frequency 0.25 Hz, amplitude 45
      degrees) about an earth horizontal and about an earth vertical axis
      (respectively, "with" and "without" otolith stimulation). Before centrifugation
      the gain of the slow component velocity (SCV) was significantly lower "with"
      otolith stimulation than "without" otolith stimulation. Apparently, the
      contribution of the otoliths counteracts the ocular torsion response generated by
      the semicircular canals. Therefore, the observed increase in SCV gain in the
      condition "with" otolith stimulation after centrifugation, seems in
      correspondence with the decreased otolith gain in the static condition.

PMID- 8886356
TI  - Neural network simulations of the primate oculomotor system. II. Frames of
      reference.
AB  - Theories of motor control often assume that the location of visual stimuli is
      expressed in non retinotopic frames of reference. The saccadic system is known in
      enough detail for us to examine the evidential basis of this assumption. The
      organization of the neural circuit that controls saccades is first summarized. It
      is shown to consist of at least two interconnected modules. The first one is the
      burst generator, which resides in the reticular formation, and is entrusted with
      the tasks of impedance matching, synergist coactivation and reciprocal inhibition
      between antagonists. The second is a metric computer, which resides in the
      superior colliculus and the cerebral cortex, and computes the size and direction
      of the desired movement. Alternative models of the burst generator are presented
      and their "verisimilitude" is assessed in the light of evidence concerning
      saccadic trajectories, neuronal discharge patterns, interneuronal connections, as
      well as the results of lesion and stimulation experiments. Several models of the
      "metric computer" in the superior colliculus are then examined; their performance
      is again evaluated in the light of psychophysical, anatomical, physiological, and
      clinical evidence. It is demonstrated that the location of visual stimuli need
      not be expressed in nonretinotopic frames of reference for either the burst
      generator or the metric computer to issue appropriate commands to move the eyes.
      Instead, using information concerning intervening movements of the eyes to update
      the location of visual stimuli in a retinotopic frame of reference suffices for
      the planning and execution of correct saccades. More generally, it is proposed
      that the location of sensory stimuli need not be expressed in higher order frames
      of reference (e.g., centered in the body or even in extrapersonal space) provided
      that their location in a sensorium specific map is updated on the basis of
      effector movements.

PMID- 8886357
TI  - NMDA receptors of the vestibular nuclei neurones.
AB  - Cloning and pharmacological studies have shown that glutamatergic receptors can
      be divided in two classes (refer to Table 1): ionotropic receptors including N
      methyl-D-aspartate (NMDA) and non-NMDA subtypes, and the G-protein-coupled
      metabotropic receptors (glutamate metabotropic receptor). There are two types of
      non-NMDA receptors: the AMPA/low-affinity kainate receptor type (the AMPA
      receptors) activated by a specific agonist, the alpha-amino-3-hydroxy-5-methyl-4
      iso-xalone propionate (AMPA), and the high affinity kainate receptors. The
      vestibular nuclei neurones are endowed with all these types of glutamatergic
      receptors, which fits well with the fact that various afferents, including the
      primary vestibular afferents, most probably use glutamate or aspartate as a
      neurotransmitter. This article is aimed at summarising several past studies of
      our group and some more recent data obtained in the in vitro whole-brain
      preparation concerning the NMDA receptors of the central vestibular neurones. In
      that process, we will detail also many valuable studies of other groups that had
      been devoted to the same topic.

PMID- 8886358
TI  - Otoconial alterations after embryonic development in hypergravity.
AB  - The relation between prolonged hypergravity and structural adaptation of otoconia
      was studied in hamsters (n = 56). Three groups of hamsters (n = 27), were
      conceived and born in a centrifuge: group 1 (n = 10) 1 month under 2.5 G, group 2
      (n = 9) 5 months under 2.5 G and 4 months under 1 G, group 3 (n = 8) 1 month
      under 2.5 G and 8 months under 1 G. Control hamsters (n = 29) were conceived and
      born under 1 G (1 month old, n = 7; 9 months old, n = 22). Histological study of
      the otoconial layers (energy dispersive x-ray element analysis and scanning
      electron microscopy) showed similar calcium content, size, and shape in utricular
      and saccular otoconia in all groups. Different were the utricular otoconial size
      classes, large, medium-sized, and small. The area with small otoconia increased
      in group 1 (p = 0.002). In group 2, the large otoconial area decreased (p =
      0.001) and the medium-sized one increased (p < 0.001). In group 3, the large
      otoconial area decreased (p = 0.003) and the medium-sized one increased (p =
      0.007). For age-related effects we found group 1 with an increased area of large
      otoconia (p = 0.001) and a decreased medium-sized one compared to groups 2 (p <
      0.001) and 3 (p = 0.02). Hypergravity during formation of otoconia does not
      affect calcium content, size, or shape, but changes relative size of the areas
      with large, medium-sized, or small otoconia and the development of these areas.
      This resulted in a structural adaptation to hypergravity.

PMID- 8886359
TI  - Influence of visual signals on the coordination of spontaneous eye and head
      movements in infant rabbits.
AB  - Horizontal angular movements of eye, head, and trunk were simultaneously recorded
      in spontaneously behaving unrestrained rabbits in the period after postnatal eye
      opening. The recordings were performed in daylight as well as in darkness. A
      crosscorrelation analysis of the velocities of eye in head and of head to trunk
      during periods of exploratory activity showed that the resulting crosscorrelation
      functions were mainly determined by the correlation of coupled saccadic movements
      of eye and head. Already at the end of the third postnatal week, the maxima of
      the crosscorrelation functions were higher and their time shifts were shorter for
      movements in light than for movements in darkness. These observations suggest
      that the stronger coupling of saccadic eye and head movement velocities in
      response to light reflects a light-induced increase in the activity of premotor
      neurons of the superior colliculus.

PMID- 8886360
TI  - Delayed visual maturation in infants: a disorder of figure-ground separation?
AB  - Delayed visual maturation (DVM) is characterised by visual unresponsiveness in
      early infancy, which subsequently improves spontaneously to normal levels. We
      studied the optokinetic response and recorded pattern reversal VEPs in six
      infants with DVM (aged 2-4 months) when they were at the stage of complete visual
      unresponsiveness. Although no saccades or visual tracking with the eyes or head
      could be elicited to visual objects, a normal full-field rapid buildup OKN
      response occurred when viewing biocularly or during monocular stimulation in the
      temporo-nasal direction of the viewing eye. Almost no monocular OKN could be
      elicited in the naso-temporal direction, which was significantly poorer than
      normal age-matched infants. No OKN quick phases were missed, and there were no
      other signs of "ocular motor apraxia." VEPs were normal in amplitude and latency
      for age. It appears, therefore, that infants with DVM are delayed in orienting to
      local regions of the visual field, but can respond to full-field motion. The
      presence of normal OKN quick-phases and slow-phases suggests normal brain stem
      function, and the presence of normal pattern VEPs suggests a normal retino
      geniculo-striate pathway. These oculomotor and electrophysiological findings
      suggest delayed development of extra-striate cortical structures, possibly
      involving either an abnormality in figure-ground segregation or in attentional
      pathways.

PMID- 8886361
TI  - Head coordination in the sagittal plane in toddlers during walking: preliminary
      results.
AB  - In adults, head rotations in the pitch plane are highly synchronized with
      vertical head translations during different locomotor tasks as walking, running,
      and hopping. The head is rotating up then down in the pitch plane as stepping
      movement drives the head down then up, respectively. The purpose of our study was
      to determine at which period of the motor control development this fine head
      coordination occurred. The organization of head movements was analyzed in four
      normal children observed longitudinally from the onset of walking up to 80 weeks
      of independent walking (IW). The degree of synchronization between vertical head
      translations and head rotations in the pitch plane was used to define an index of
      head coordination for 15 to 25 steps per child per session. Our results show that
      the coordination of head rotations in the pitch plane improves continually in
      toddlers but does not reach the optimal level during the first year of IW
      experience. We showed previously that head stabilization in space was achieved
      during the first weeks of IW. Both head stabilization in space and fine head
      coordination during walking are considered as directly involved in gaze
      stabilization, but in toddlers head stabilization in space is completed earlier
      than head coordination. Head stabilization appears to be a necessary motor
      control to acquire prior to the development of head movement coordination.

PMID- 8886362
TI  - The subjective visual horizontal for different body tilts in the roll plane:
      characterization of normal subjects.
AB  - In order to establish a method for estimation of the perceptual horizontal as a
      test of otolith function in diagnosis of atypical vertigo, in a first study we
      have standardized a test procedure and characterized a body of normal material
      consisting of 72 healthy subjects, 24 of them examined with tests followed by
      retests. The perceptual visual horizontal in darkness was estimated in the
      upright body position and at body tilts of 10, 20, and 30 degrees to the right
      and to the left by means of a narrow luminous bar. The deviation of the
      perceptual horizontal relative to the gravitational horizontal is expressed as a
      function of body tilt. In the upright body position, 95% had a perceptual
      horizontal within the range of +/- 2.5 degrees. In the tilted positions, there
      was a tendency to set the light bar tilted oppositely with respect to the body
      tilt. The results suggest that roll tilt to the right and to the left is sensed
      by two independent functional units. Furthermore, the results imply that some
      other factor might be of importance and that the perceptual horizontal in the
      upright position and tilt perception are complementary in reflecting vestibular
      function. Differences between individuals were great in comparison with
      intraindividual variability and the test-retest variability. The results are
      discussed against the background of the extensive literature.

PMID- 8886363
TI  - The subjective horizontal at different angles of roll-tilt in patients with
      unilateral vestibular impairment.
AB  - The subjective visual horizontal is mainly dependent on the otolithic system. A
      group of 11 patients with sudden unilateral vestibular impairment were asked to
      set a dimly illuminated bar according to their subjective horizontal when they
      were seated upright and tilted 10, 20, and 30 degrees to the right and left in a
      completely darkened room (Bias test). The patients were examined within 1 week,
      after 3 and 6 weeks, and 9 patients consented to the 11-week follow-up. The
      results were compared with ENG examinations. In the acute stage of the disease
      all patients, when they were in upright position, set the light bar tilted
      towards the affected side. At roll tilt to the affected side, 9 of the 11
      patients set the light bar in the same direction as their body tilt
      (undercorrection). At a tilt to the unaffected side 6 of the 11 patients made an
      undercorrection. For the group of patients the magnitude of undercorrection was
      larger at tilt to the affected side than to the unaffected side. The patients'
      ability to correctly align the light bar with the true horizontal gradually
      improved but was found normal in both upright and tilted positions in only three
      of the nine patients at the last follow-up. In four of the six patients who still
      demonstrated pathologic results, these were met only in tilted positions. No
      significant correlation was found between the intensity of spontaneous nystagmus
      or the degree of caloric side difference and the deviation in setting of the
      light bar in upright or tilted positions. The large asymmetric perceptual
      responses at tilt found at onset might be explained by the two-directional
      organisation of the utricle.

PMID- 8886364
TI  - Perceived body position and the visual horizontal.
AB  - This contribution examines the relation between the subjective visual vertical,
      the subjective visual horizontal, and the perceived body position of human
      subjects. Firmly fixed on a tiltable chair with head and torso restrained, 11
      healthy subjects were rolled sideways and indicated their subjective horizontal
      body position. In these positions the subjects were also asked to adjust a
      luminous line alternately to the vertical and to the horizontal. The adjustments
      of the subjective horizontal body position cluster around a mean of 96.3 degrees
      with a remarkably broad range (SD: 19.7 degrees). In the subjective horizontal
      body position, the luminous line does not appear horizontal when in line with
      one's own spinal axis. It is set further down by 27.4 degrees on average and,
      therefore, perpendicular to the subjective visual vertical. This finding supports
      the idea that the judgement of the own body position and the judgement of the
      orientation of a seen object respective to gravity are based on different
      references. Contradictory to other investigations [23,24], is the empirical fact
      that the individual subjects were not able to adjust the horizontal body position
      with the reported accuracy (range of mean adjustments 77.5 to 117.6 degrees).

PMID- 8886365
TI  - The role of ocular torsion in visual measures of vestibular function.
AB  - This brief review highlights problems in the interpretation of results about
      perceived postural roll-tilt of human subjects undergoing roll-tilt around their
      naso-occipital axis, when visual stimuli are used as a means of indicating
      perception. The otolithic stimulus, which causes the changes in perceived
      posture, also causes the eyes to roll (or tort). In turn, the altered torsional
      position of the eye causes the perceived orientation of visual stimuli to change.
      Consequently, indicators of postural perception, which rely on visual stimuli,
      are a confounded combination of two factors; the person's perceived postural roll
      tilt, and the effect of the otolithic stimulus on ocular torsional position.
      Consequently, settings of a visual stimulus do not permit direct unambiguous
      interpretation of a subject's perceived postural roll-tilt.

PMID- 8886366
TI  - The delay of the oculogravic illusion.
AB  - Previous measures of roll-tilt sensation during combined angular and linear
      acceleration during off-center rotation have found a heading-dependent delay in
      reaching a stable sensory value. This delay has been attributed to sensory
      conflict between the canal and otolith signals. Another possibility is that the
      visual indicator used to measure this sensation may have been responsible for the
      heading-dependent difference. This study used a somatosensory task, which is free
      from such artifacts and still showed a significant heading-dependent delay. We
      conclude that in analyzing canal-otolith interaction it is necessary to take into
      account the direction of the linear acceleration with respect to the activated
      canal.

PMID- 8886367
TI  - Subjective postural vertical inferred from vestibular-optokinetic vs.
      proprioceptive cues.

PMID- 8886368
TI  - Shift of subjective reference and visual orientation during slow pitch tilt for
      the seated human subject.
AB  - We examined the ability to assess subjective orientation and orientation of an
      external visual object during pitch tilt. Subjects were seated, restrained, and
      in darkness in a simulator and estimated when they were 0 degree, 45 degrees, and
      90 degrees forwards and backwards from upright during pitching at 1 degree/s.
      They temporarily stopped in these positions and set a 5 cm luminous cube, cockpit
      mounted at 60 cm from the nasium, to earth vertical. Estimates of subjective tilt
      were consistently greater than actual tilt. Overestimations were increased by
      preceding tilts in the opposite direction, particularly when tilting from
      forwards, where subjects sometimes estimated they were tilted backwards when the
      machine was tilted forwards. Subjects were surprised with their estimates, and
      reported disorientation. Regardless, settings of the visual vertical made
      "intuitively" were largely accurate. Subjective estimates could be construed as
      "accurate" if one assumes that the rostro-caudal axis of the head was referenced
      for estimates of upright and forwards and a trunk-leg axis for backwards. Because
      labyrinthine defective patients behaved as normal subjects, task performance must
      have been based on proprioception. The overestimation of tilt is exploited in
      fairground illusions and may account for the common experience when driving, that
      hills seem much steeper than they are.

PMID- 8886369
TI  - Can a unilateral loss of otolithic function be clinically detected by assessment
      of the subjective visual vertical?
AB  - Asymmetries in the settings of the subjective visual vertical after unilateral
      vestibular neurectomy during eccentric centrifugation [3] might provide a
      clinical test for unilateral otolithic function. This study investigates whether
      these asymmetries can also be revealed by a technically much easier practicable
      roll tilt of the subject relative to gravity instead of a roll tilt of the
      gravitational force on a human centrifuge. Twenty-seven normal subjects and 13
      patients before surgery indicated verticality very accurately in the upright
      position. In 26 degrees roll positions (subjects seated on a slanted chair), they
      were only slightly more variable with no asymmetries larger than 5.3 and 7.8
      degrees in normals and preoperative patients, respectively, between the roll
      positions toward the healthy and toward the affected ear. One week after surgical
      unilateral vestibular deafferentation, there was a consistent shift (mean 11.9
      degrees) of the subjective vertical toward the affected ear in all patients and
      in all body positions. When the settings in the two roll tilt positions were
      referred to the setting in upright position, the group means of the patients were
      symmetrical although single subjects revealed asymmetries up to 22.4 degrees.
      Only one of four patients who were tested also during eccentric rotation revealed
      an important asymmetry with decreased sensitivity for tilts of the gravitational
      vector toward the affected ear. Measuring the subjective visual vertical assesses
      only asymmetrical tonic otolithic input, while a simple clinical test for
      unilateral otolithic sensitivity still has to be found.

PMID- 8886370
TI  - Control of the body vertical by vestibular and proprioceptive inputs.
AB  - The study examines the influence of vestibular and leg proprioceptive cues on the
      maintenance of the body vertical in human stance. Vestibular body orientation
      cues were changed by applying bipolar currents to both mastoid bones (cosine-bell
      wave form of 3.3 s duration, 1 mA current intensity). Proprioceptive input was
      modified by vibrating the tibialis anterior muscle (at f = 90 Hz, step of 5 s
      duration and 1 mm amplitude). Furthermore, the vestibular stimulus was paired
      with the muscle vibration using three different temporal relationships between
      the stimuli. Body lean responses were analyzed in terms of sway trajectories of
      the center of foot pressure on the body support surface (horizontal plane). With
      the anode on the right mastoid, vestibular body lean response was essentially
      straight towards the right side, and with the anode on left mastoid towards the
      left side. Vibration of right tibialis anterior muscle induced an almost straight
      body lean forward and to the right. Upon combined stimulation, responses with
      complex trajectory resulted, which depended on the stimulus interval. These
      responses reflected a superposition of the individual vestibular and
      proprioceptive effects. The results show that the body vertical is under the
      continuous control of leg proprioceptive and vestibular inputs, which sum
      linearly. We present a concept according to which these inputs are used for
      establishing a reference system for the control of the body vertical.

PMID- 8886371
TI  - The effect of eye/head deviation and visual conflict on visually evoked postural
      responses.
AB  - Three interrelated experiments on visually evoked postural responses (VEPR) are
      presented to investigate the effect of lack of coplanarity between retinal and
      body coordinates (Experiment I) and the effect of directionally conflicting
      information in the visual stimulus. Experiment I showed that the direction of
      VEPR is modified by eye-in-orbit and head-on-trunk position signals, presumably
      of proprioceptive origin. Experiments II and III showed that VEPR can be
      critically suppressed by the presence of conflict within the visual stimulus
      (Experiment II: a linear, tangential component of visual motion acting in the
      opposite direction to the main angular component of a roll-motion display;
      Experiment III: a non congruent "improbable" visual motion parallax linear motion
      stimulus). A conceptual model of the postural system is presented, incorporating
      a gain control unit for the visuo-postural loop with inputs from the
      ocular/cervical proprioceptive system and from intra- and inter-sensory conflict
      detectors (comparators).

PMID- 8886372
TI  - Thresholds for detection of motion direction during passive lateral whole-body
      acceleration in normal subjects and patients with bilateral loss of labyrinthine
      function.
AB  - To investigate the effect of velocity, acceleration, and gradient of acceleration
      on self-motion perception, thresholds for detection of direction of whole-body
      interaural acceleration were determined for various stimulus profiles. For
      acceleration steps, acceleration thresholds at 67% correct detection of motion
      direction were similar for eight normals (mean 4.84 cm/s2 (range 2.9-6.3), peak
      gradient = 22 cm/s2) and five labyrinthine-defective subjects (mean 5.65 cm/s2
      (4.85-6.6), peak gradient = 25 cm/s2). Velocity thresholds were 7.93 cm/s for a
      proportion of correct responses of 73% for normals and 9.67 cm/s for 69% of
      correct detection for avestibular subjects. For linear and parabolic
      accelerations, high intersubject variability was observed both among nine normals
      and three labyrinthine-defective subjects. Mean normal and avestibular subjects'
      acceleration thresholds for 74% of correct responses were respectively 12.1 cm/s2
      (7.3-20.4) and 16.4 cm/s2 (13.2-20) for a ramp with gradient of acceleration =
      2.8 cm/s3, 19.2 cm/ s2 (10.4-35.3) and 28.2 cm/s2 (21.4-32.8) for a ramp with
      gradient = 7.9 cm/s3 and 16.7 cm/s2 (10.5-25) and 20.6 cm/s2 (18.4-24.2) for a
      parabola with second derivative = 1.52 cm/s4. The corresponding velocity
      thresholds for normals were 21.2 cm/s (5.2-50.3), 22.0 cm/s (7-56.6), and 22.2
      cm/s (9.5-43.7). The lowest thresholds were obtained for acceleration steps
      indicating that a high acceleration gradient facilitates motion perception. For
      linear and parabolic accelerations, motion perception seemed to follow an
      integration of acceleration, but a high intersubject variability was observed.
      For all stimuli, the range of thresholds for normals and avestibular subjects
      overlapped showing that detection of motion was not a sole prerogative of the
      otoliths but could also be performed using somatosensory cues.

PMID- 8886373
TI  - Detection thresholds for object motion and self-motion during vestibular and
      visuo-oculomotor stimulation.
AB  - We compared the detection threshold for object motion with that of self-motion in
      space in healthy human subjects. Stimuli consisted of horizontal rotations of
      subjects' body with a fixation spot kept in fixed alignment with their heads
      (vestibular stimulus), rotation of the fixation spot relative to the stationary
      subjects (visuo-oculomotor stimulus), and a combination thereof by applying
      rotations of subjects body relative to the stationary object (sinusoidal
      oscillations, 0.025-0.4 Hz). Two series of experiments were performed. 1) One
      group of subjects was instructed to attend to, and to indicate the occurrence of,
      either object or self-motion. 2) A second group was instructed not only to detect
      the occurrence of a perception, but also to quality it either as object motion or
      self-motion, depending on which modality dominated perceptually. With either
      instruction it was found that all three stimulus conditions could evoke both,
      either an object motion perception or a self-motion perception. The detection
      thresholds of both perceptions were essentially similar. Thresholds were highest
      with the vestibular stimulus, intermediate with the stimulus combination, and
      lowest with the visuo-oculomotor stimulus. The vestibular threshold depended on
      stimulus frequency, in that it decreased with increasing frequency. Thereby, it
      became similar to the visuo-oculomotor one, which was essentially constant across
      frequency. Probability of occurrence of the perceptions in the first experimental
      series was considerably higher than in the second series, suggesting an important
      role of attentional mechanisms. In the second series, percent frequency of
      occurrence of veridical perception (object motion with visuo-oculomotor stimulus,
      self-motion with stimulus combination) was at chance level (50%) at low stimulus
      frequency, but was augmented considerably at high frequency. We assume that the
      latter effect is brought about by a visual-vestibular conflict measure by which
      the visual stimulus (light spot) is qualified as representing either a moving
      object or a spatial reference for self-motion. While at suprathreshold stimulus
      intensities the conflict can determine perception magnitude, at threshold levels
      its influence is restricted mainly on the probability of occurrence of object and
      self-motion perception.

PMID- 8886374
TI  - Object motion perception during ego-motion: patients with a complete loss of
      vestibular function vs. normals.
AB  - Object motion perception was assessed in avestibular patients and normal
      controls. Two experiments were conducted, in which subjects were required to
      assess the motion of a visual stimulus with respect to earth. In the first
      experiment, we measured the velocity at which a briefly presented (200 ms)
      grating was perceived as earth fixed, while the subject maintained fixation on a
      visual target fixed relative to the body, during whole-body yaw rotation (VOR
      suppression). In this experimental setup, the influence of the semicircular canal
      signals on object motion perception was evaluated. The avestibular patients
      judged the grating to be stationary with respect to earth, when it was moving at
      the same velocity as their body, whereas for normal controls, the grating was
      perceived as stationary when it moved at a velocity slower than their body
      motion, but greater than zero. The difference between the two subject groups was
      significant, and showed the strong contribution of the vestibular system to
      object motion perception. Similarly, a measurement of the velocity at which a
      grating was perceived as stationary was obtained during smooth pursuit eye
      movements. In this experiment the contribution of the efference copy of the
      oculomotor signal and proprioceptive signals to object motion perception were
      assessed. As with the first experiment, the normal controls displayed a more
      veridical sense of object motion perception than the patients, although the
      difference was only just significant. We suggest that the difference could be an
      adaptive change in the patients perception of motion, which allows them to reduce
      the effects of oscillopsia.

PMID- 8886375
TI  - Is perceived angular displacement the time integral of perceived angular
      velocity?
AB  - Estimates of rotational self-displacement and self-velocity have been used
      interchangeably in vestibular psycho-physics to characterize vestibular ego
      motion perception. However, the assumption underlying this indiscriminate use has
      never been tested. The assumption holds that the two estimates are equivalent,
      with the displacement estimates reflecting the time integral of the signal
      underlying the velocity estimate. We tested this hypothesis by directly comparing
      displacement and velocity estimates. Two groups of healthy young subjects (2 x n
      = 15) were presented with the same vestibular stimuli (horizontal whole body
      rotations in the dark in the form of velocity steps of 5, 10, 20, and 40
      degrees/s with 1, 2, 4, 8, and 16 s duration, yielding position ramps of 5, 10,
      20, 40, 80, 160, and 320 degrees total displacement). The first subject group
      estimated peak velocity, and the second group estimated total displacement, both
      groups using a comparable psychophysical procedure (Stevens' magnitude
      estimation). The experimentally obtained velocity estimates were used to predict
      the displacement estimates. To this end, the velocity signal was assumed to decay
      exponentially from the reported peak value (reflecting the dynamics of peripheral
      and early central vestibular mechanisms) and was mathematically integrated.
      Predicted and measured displacement estimates were similar when a time constant
      of 20 s was assumed, which is in good agreement with earlier studies. We conclude
      that vestibular displacement estimates can, indeed, be considered equivalent to
      vestibular velocity estimates, at least for the stimulus parameters used.

PMID- 8886376
TI  - Simulating self-motion.
AB  - In general, vehicle motions far exceed the mechanical constraints of an earth
      fixed simulator base. Inertial motions can, therefore, only be simulated in
      partial agreement with those of the actual vehicle. As a consequence, physical
      mismatches between inertial and environmental motion are inevitable. Here, the
      concept of a subjective reference frame is introduced, relative to which
      perceived self-motion is defined. This frame must be released from the earth
      fixed frame to evoke simulated self-motion. In addition, self-motion and
      environmental motion need to be perceived reciprocal, in order to evoke a
      stationary perceived environment. Due to the only limited accuracy of human self
      motion perception, however, perceived self-motion and perceived environmental
      motion need not to be exactly reciprocal. The extent to which self-motion and
      environmental motion may differ can be expressed by a just noticeable difference.
      This just noticeable difference denotes the threshold at which the environment is
      perceived to move. In this article, a self-motion perception model is outlined in
      which perceived environmental motion and perceived self-motion are separated. The
      perception model and the just noticeable differences can then be applied to
      determine the inertial stimulation that is needed to evoke perceived self-motion,
      in which the environment is perceived stationary throughout simulation.

PMID- 8886377
TI  - Processing the head direction cell signal: a review and commentary.
AB  - Animals require information about their location and directional heading in order
      to navigate. Directional information is provided by a population of cells in the
      postsubiculum and the anterior thalamic nuclei that encode a very accurate,
      continual representation of the animal's directional heading in the horizontal
      plane, which is independent of the animal's location. Recent studies indicate
      that this signal 1) arises either in the anterior thalamic nuclei or in
      structures upstream from it; 2) is not dependent on an intact hippocampus; 3)
      receives sensory inputs from both idiothetic and landmark systems; and 4)
      correlates well with the animal's behavior in a spatial reference memory task.
      Furthermore, HD cells in the anterior thalamic nuclei appear to encode what the
      animal's directional heading will be about 40 ms in the future, while HD cells in
      the postsubiculum encode the animal's current directional heading. Both the
      electrophysiological and anatomical data suggest that the anterior thalamic
      nuclei and/or the lateral mammillary nuclei may be the sites of convergence for
      spatial information derived from landmarks and internally-generated cues. Current
      evidence also indicates that the vestibular system plays a crucial role in the
      generation of the HD cell signal. However, the notion that the vestibular system
      is the sole contributor to the signal generator is difficult to reconcile with
      several findings; these latter findings are better accounted for with a motor
      efference copy signal.

PMID- 8886378
TI  - Space and the hippocampal formation in humans.

PMID- 8886379
TI  - Quantitative analysis of human walking trajectory on a circular path in darkness.
AB  - Thirteen normal (eight young and five older) subjects and a patient who was
      removed left sided acoustic neurinoma were tested to walk blindfolded along
      circular paths. They were asked to walk completing two revolutions and to stop
      when they judged they had returned to the initial position with their head faced
      to the initial directions. Movements of two markers on the subjects head were
      recorded by three dimensional motion analyzing system (ELITE system) at 50 Hz
      which allowed us to measure (a) total walked distance, (b) average radius of the
      trajectory, and (c) cumulative angle of rotation. Eight young subjects were
      tested on three circles with radii 0.5, 0.9, and 1.15 m, in two conditions
      (control, and with mental arythmetic), only to clockwise direction. Five older
      subjects and a patient were tested on a circle of 0.9 m radius in two conditions,
      but to both directions, counterclockwise and clockwise. Walked trajectories of
      young subjects were smooth, whereas those of older subjects tended to be
      polygonal. Young subjects overshot the ideal distance (6.6%) and ideal radius
      (9.5%), whereas they undershot the ideal angle (5.1%). There was no effect of
      circle size or condition on these variables. On the other hand, there was a
      significant effect of condition on average radius in the older group. The
      performance of older subjects seemed to be affected by the concurrent mental
      task. Comparing the counterclockwise walk, the older subjects undershot the
      turning angle much more than the young subjects which suggest deficits in the
      vestibular function with aging. The patient showed larger radius and smaller
      angle while she turned to the healthy side (clockwise) than to the affected side
      (counterclockwise). Lack of unilateral vestibular information seemed to have
      affected the circular walking trajectory.

PMID- 8886380
TI  - When is a view unusual? A single case study of orientation-dependent visual
      agnosia.
AB  - Several hypotheses have been proposed to explain why some neurological patients
      fail to recognise objects from unusual views: that it results from difficulty
      identifying an object's principal axis when it is foreshortened, identifying an
      object when landmark features are occluded, or an inability to rotate mental
      images. It was possible to test these hypotheses by examining the recognition
      abilities of a single case (A.S.), by using stimuli that were "unusual" only
      because of picture-plane misorientation. A.S. showed a recognition deficit in
      which his accuracy was proportional to the extent of misorientation from the
      normal upright for the object-although both principal axis and feature
      information remain visible after picture-plane rotation. Furthermore, A.S.
      performed with normal accuracy, and normal pattern of reaction time performance,
      on tasks of mental rotation. These findings suggest that none of these
      traditional accounts can adequately explain why this patient was unable to
      recognise objects from unusual views. These findings are discussed the light of
      recent suggestions of the basis of this type of disorder.

PMID- 8886381
TI  - Spatial orientation perception and reflexive eye movements--a perspective, an
      overview, and some clinical implications.
AB  - When head motion includes a linear velocity component, eye velocity required to
      track an earth-fixed target depends upon: a) angular and linear head velocity, b)
      target distance, and c) direction of gaze relative to the motion trajectory.
      Recent research indicates that eye movements (LVOR), presumably otolith-mediated,
      partially compensate for linear velocity in small head excursions on small
      devices. Canal-mediated eye velocity (AVOR), otolith-mediated eye velocity
      (LVOR), and Ocular Torsion (OT) can be measured, one by one, on small devices.
      However, response dynamics that depend upon the ratio of linear to angular
      velocity in the motion trajectory and on subject orientation relative to the
      trajectory are present in a centrifuge paradigm. With this paradigm, two 3-min
      runs yields measures of: LVOR differentially modulated by different subject
      orientations in the two runs; OT dynamics in four conditions; two directions of
      "steady-state" OT, and two directions of AVOR. Efficient assessment of the
      dynamics (and of the underlying central integrative processes) may require a
      centrifuge radius of 1.0 meters or more. Clinical assessment of the spatial
      orientation system should include evaluation of central integrative processes
      that determine the dynamics of these responses.

PMID- 8886382
TI  - Physiological and pathophysiological roles of nitric oxide in the central nervous
      system.
AB  - Nitric oxide (NO) is produced by three distinct isoforms of nitric oxide
      synthases in the central nervous system. Here, the roles of nitric oxide in the
      central nervous system are reviewed under physiological and pathophysiological
      conditions. Under physiological conditions, NO plays a role in the regulation of
      cerebral blood flow and autoregulation, blood flow-metabolism coupling,
      neurotransmission, memory formation, modulation of neuroendocrine functions, and
      behavioral activity. Impairment of the NO-mediated cerebrovascular vasodilatation
      occurs during ischemia-reperfusion, diabetes, hypertension, subararchnoid
      hemorrhage, and various forms of shock. Enhancement of NO production in the brain
      occurs during stoke, seizures, and acute and chronic inflammatory and
      neurodegenerative disorders. The alterations of the expression of the various
      isoforms of nitric oxide synthases under the above conditions are discussed.
      Moreover, the molecular mechanisms of NO and peroxynitrite induced cellular
      injury are delineated. Finally, the current strategies available for selective
      pharmacological manipulation of individual nitric oxide synthase isoforms are
      discussed.

PMID- 8886383
TI  - Noninvasive dopamine determination by reversed phase HPLC in the medium of free
      floating roller tube cultures of rat fetal ventral mesencephalon: a tool to
      assess dopaminergic tissue prior to grafting.
AB  - The low availability of dopamine containing neurons for grafting in Parkinson's
      disease is a general problem. Free-floating roller tube (FFRT) cultures allow
      storage of fetal mesencephalic tissue prior to transplantation. Preoperative
      functional testing permits to select an optimized set of individual cultures for
      transplantation. Rat fetal ventral mesencephali (E13) were dissected out and
      divided into four equally sized pieces each and individually prepared as FFRT
      cultures. After 4, 8, 12, and 16 days in vitro (DIV) the medium of each culture
      was collected during routine medium change and immediately stabilized. Dopamine
      was extracted and probes were determined with reversed phase HPLC using electro
      chemical detection. After 16 DIV cultures were fixed and cell counts performed in
      tyrosine hydroxylase (TH)-immunostained serial sections. The mean dopamine
      content +/- SEM In culture conditioned media was at 4 DIV: 21 +/- 2 pg, n = 38;
      at 8 DIV: 37 +/- 4 pg, n = 40; at 12 DIV: 52 +/- 7 pg, n = 38; and at 16 DIV: 39
      +/- 5 pg, n = 38. In all cultures devoid of dopamine after 4 and 8 DIV (12.5%)
      levels remained below detectability at 12 and 16 DIV. Cultures derived from the
      rostral mesencephalon showed significantly higher dopamine values than those from
      the caudal mesencephalon at 12 DIV. The mean number of TH-immunoreactive (-ir)
      cells/culture +/- SEM after 16 DIV was 556 +/- 51, n = 40. The correlation
      between TH-ir cell number (CN) and dopamine content of rostrally derived cultures
      at 16 DIV was: CN = 7.4 (dopamine [pg]) + 248; R = 0.75; n = 19; p < 0.001. No
      dopamine was present in cultures without TH-ir cells. These results demonstrate
      that sequential noninvasive screening of dopamine in single cultures is feasible
      and that the dopamine content is correlated to the number of surviving TH-ir
      cells. This permits to select cultures rich in dopaminergic neurons for
      transplantation.

PMID- 8886384
TI  - A stereotaxic atlas of the basal ganglia in macaques.
AB  - Maps of the striatum, pallidum and subthalamic nucleus were established in two
      macaque species (Macaca mulatta and Macaca fascicularis) in stereotaxic
      coordinates. The cartographic method relied on the use of intracerebral,
      ventricular landmarks (CA: anterior commissure and CP: posterior commissure). The
      basal ganglia outlines, first drawn in transverse sections perpendicular to the
      CA-CP plane, were reconstructed on the horizontal and midsagittal planes. Maps
      from several individuals were superimposed and statistical variations studied.
      The results confirm that the length between the two CA and CP points is
      statistically greater (7%) in the Macaca mulatta than Macaca fascicularis but
      reveal considerable inter-individual differences. The closer a given nucleus is
      from a ventricular reference point, the more stable its outline. Superimpositions
      led to a statistical determination of the stereotaxic coordinates required to
      reach a given target center. Comparison of the lateralities with those measured
      in six previously published atlases indicates that the brain mapped by Snider and
      Lee [17] is the smallest and that mapped by Olszewski [8] is the largest.

PMID- 8886385
TI  - Bilateral striatal lesions impair retention of an operant test of short-term
      memory.
AB  - It has been previously shown that lesions of the dorsal striatum can disrupt
      performance on a variety of cognitive tasks related to prefrontal cortex
      function. In order to extend these studies, we have compared the effects of
      bilateral striatal lesions on retention of an operant test of short-term memory
      using a delayed matching to position task. Rats were initially pretrained on the
      matching task. Then, one group of animals received ibotenic acid lesions in the
      dorsal striatum and a second group received sham lesions. The striatal lesions
      induced marked deficits on delayed matching performance when the rats were
      retested one week following surgery. The delay-independent pattern of deficit
      observed does not suggest a primary impairment in short-term memory function. The
      lesion induced deficits were temporary, with recovery seen in the lesion group
      back to a control level of performance in 2 additional test sessions 5 and 10
      weeks post-lesion. A follow up study investigating the time course of the deficit
      suggests that the recovery seen in performance measures cannot be attributed to
      the elapse of time per se, but rather is due to re-learning. In addition to the
      performance deficits in the operant task, the lesioned rats exhibited marked
      nocturnal locomotor hyperactivity. The results indicate that bilateral striatal
      lesions induce marked deficits in retention of the delayed matching to position
      task. They suggest a key role for the neostriatum in the execution of pre-learned
      responses, but do not exclude the possibility of additional involvement in short
      term memory functions under certain testing conditions.

PMID- 8886386
TI  - Water versus salty taste and Iontophoretic ANGII responses of septopreoptic
      neurons in dehydrated and euhydrated awake rats.
AB  - Little is known of the influence of gustatory, particularly salt, input on
      neurons of the forebrain and if the same neurons are sensitive to hydromineral
      balance humoral stimuli. In awake, nonpremedicated rats we recorded the activity
      of spontaneously active neurons in the preoptic/anterior hypothalamic area of
      dehydrated and euhydrated rats while allowing them to ingest water or a
      hypertonic salt solution (1.6% NaCl) administered to the tongue. The hormones
      angiotensin and aldosterone, both implicated in hydromineral balance, were
      applied by iontophoresis to the same neurons. In the dehydrated rats, 27% (15/55)
      of the spontaneously active neurons responded to a liquid (either water or the
      NaCl) applied to the tongue; in the euhydrated rats 23% (18/78) responded to the
      same stimuli. In the dehydrated rats, however, 33% (5/15) of the responding
      neurons were inhibited when the NaCl solution was applied to the tongue compared
      with only 5% (1/18) in the euhydrated rats. Iontophoretic application of
      angiotensin increased the spontaneous activity in 21% of those neurons tested
      that responded to taste. These results suggest that the state of hydration of an
      animal is able to change the neuronal response to substances applied to the
      tongue. Furthermore, it appears that these gustatory-sensitive neurons may also
      be related to hydromineral balance regulation since they are able to respond to
      angiotensin.

PMID- 8886387
TI  - Neonatal isolation alters LTP in freely moving juvenile rats: sex differences.
AB  - We have previously reported that neonatal isolation significantly enhanced the
      magnitude of hippocampal long-term potentiation (LTP) recorded from freely moving
      male rats tested at 30 days of age. The present study extends this work to
      examine the effects of neonatal isolation on hippocampal LTP in male and female
      juvenile rats. Changes in dentate granule cell population measures, i.e., EPSP
      slope and population spike amplitude (PSA), evoked by tetanization of the medial
      perforant pathway were used to assess the effects of neonatal isolation on LTP
      over a period of 96 hrs. Prior to tetanization, significant sex differences were
      obtained for input/output (I/O) response measures of EPSP slope and PSA, with
      males showing consistently higher values than females. No significant effect of
      treatment was obtained within either sex for baseline measures. Following
      tetanization significant sex differences were also obtained for both measures,
      with males showing significantly greater enhancement than females. Comparisons
      made at 1 hr post-tetanization (establishment of LTP) indicated that isolated
      males showed significantly greater enhancement than any other group. On the other
      hand, treatment differences were not obtained from females. At 96 hrs
      (maintenance of LTP), however, both neonatally isolated males and females showed
      significantly greater enhancement than either non-isolated siblings or unhandled
      controls. These results indicate that males and females exhibit different
      enhancement profiles with respect to both the magnitude and duration of LTP, and
      that neonatal isolation alters these profiles in a sex-specific manner.

PMID- 8886388
TI  - Electrocorticographic activity during repeated vs continuous hypoxia in piglets.
AB  - To assess the effects on brain activity of repeated vs continuous hypoxia, 16, 10
      to 22-day-old piglets were instrumented chronically for electrocortical and
      arterial pH and gas tension measurements. They inhaled 10% or 6% O2 in N2 for 21
      min, either continuously, or during seven, 3 min exposures interrupted by 3 min
      recovery periods in air, all while behaving naturally within a sealed,
      temperature controlled, plexiglass box. An isoelectric electrocorticogram (ECoG)
      and/or seizures, related to the onset of hypoxia, occurred repeatedly in 6 of the
      10 exposures to 6% repetitive hypoxia, only twice in 8 exposures to 6% continuous
      hypoxia, and never in 10% hypoxia. A frequency analysis of the ECoG, excluding
      all sections exhibiting isoelectric and seizure activity, revealed no changes
      with 10% hypoxia, but a shift towards the lower bands during both repetitive and
      continuous 6% hypoxia. The extent of these shifts was greater in records that
      also displayed isoelectric ECoG and/or seizures. The ECoG spectrum recovered at
      the end of the hypoxic exposure, but not when isoelectric ECoG and/or seizures
      coexisted. We conclude that repeated, frequent episodes of hypoxia are more
      detrimental than a prolonged single event, and may contribute to the occurrence
      of Sudden Infant Death.

PMID- 8886389
TI  - The predatory strike of free ranging praying mantises, Sphodromantis lineola
      (Burmeister). I: Strikes in the mid-sagittal plane.
AB  - The predatory behavior of free ranging praying mantises, Sphodromantis lineola
      (Burmeister), in response to prey at various positions in the midsagittal plane,
      was examined using high speed (200 frames per second) videography. Predatory
      strikes fell neatly into two categories based on the elevation of the prey from
      the surface on which the mantises stood: high strikes and low strikes. When the
      prey was 35 degrees or more above the surface (measured from the mesothoracic
      tarsus), mantises assumed a posture that elevated and pointed the body upwards
      (high strikes). When prey was near or below the surface on which the mantises
      stood, they assumed a posture that lowered the body and shifted its center of
      gravity forward (low strikes). Each of these two initial postures was followed by
      distinctly different constellations of movements, which included a rapid grasping
      movement of the raptorial forelegs and, if the prey was sufficiently distant, a
      displacement of the body upwards (high strikes) or forwards (low strikes). Our
      analyses suggest that prothoracic angle and, to a lesser degree, head angle and
      the degree to which the mesothoracic legs are extended provide the critical
      proprioceptive cues used in programming the appropriate attach sequence. Based on
      our results, we hypothesize that mantises process visual and proprioceptive
      information indicating prey location in 'pterothorax-centered space'.

PMID- 8886390
TI  - The predatory strike of free ranging praying mantises, Sphodromantis lineola
      (Burmeister). II: Strikes in the horizontal plane.
AB  - The predatory behavior of free ranging praying mantises, Sphodromantis lineola
      (Burmeister), in response to prey at various positions in the horizontal plane
      was examined using high speed (200 frames per second) videography. We found that
      the movements of the meso- and metathoracic legs over the course of the strike
      were analogous in many respects to those made by the cockroach Periplaneta
      americana during escape turns. When mantises struck at prey directly ahead of
      them, they were propelled forward by extensions of the metathoracic femur-tibia,
      and the meso- and metathoracic coxa-femur joints (changes in the latter were
      determined indirectly via changes in the femur-pterothorax angles). This pattern
      of movements is similar to that of cockroach Type 1 turns. However, when prey lay
      to either side of the pterothorax-abdomen axis, mantises turned toward the prey
      as they stuck. These turning movements were the result, primarily, of changes in
      the femur-thorax angles. Specifically, as the mantises turned toward the prey,
      contralateral mesothoracic femora and metathoracic tibiae and femora extended,
      and the corresponding ipsilateral joints extended to a lesser degree or flexed.
      This pattern of movements is similar to that of cockroach Type 2 turns. In
      addition, these leg movements were accompanied by flexion of the prothorax
      abdomen angle which turned the prothorax even further in the direction of the
      prey. We found a stronger relationship between mantis leg movements and the
      position of the prey in relationship to the pterothorax than between the leg
      movements and the position of the prey in the visual field. Our data suggest that
      the praying mantis' central nervous system integrates proprioceptive and visual
      information in order to determine the location of prey in "pterothorax-centered'
      rather than "head-centered' space.

PMID- 8886391
TI  - Telencephalo-habenulo-interpeduncular connections in the goldfish: a DiI study.
AB  - The telencephalo-habenulo-interpeduncular system has been anatomically and
      neurochemically characterized in mammals. However, little is known about these
      important forebrain-midbrain connections in non-mammalian vertebrates, although
      available data suggest that they are evolutionarily relatively conservative.
      Previous ultrastructural studies in the goldfish confirmed the presence of
      massive telencephalohabenular and habenulointerpeduncular projections and
      demonstrated a minor direct telencephalointerpeduncular connection. Here we
      report the anterograde and retrograde transport of lipophilic fluorescent
      carbocyanine dye from the interpeduncular nucleus and the habenular nuclei in the
      fixed goldfish brain. The application of dye into the interpeduncular nucleus
      resulted in massive labeling of the fasciculus retroflexus and of the habenular
      neurons. A few scattered neurons were also seen in the dorsal nucleus of area
      ventralis telencephali. Application of dye into the habenulae resulted in
      anterograde transport through the medial and lateral olfactory tracts to some
      cell bodies in the anterior and posterior zone of area ventralis telencephali and
      in perikarya of the bed nucleus and in the entopeduncular nucleus. These results
      demonstrate the origin of the direct telencephalointerpeduncular projection in
      the goldfish and confirm some important homologies with forebrain-midbrain
      projections in land vertebrates.

PMID- 8886392
TI  - Agonistic interactions affect brain serotonergic activity in an acanthopterygiian
      fish: the bicolor damselfish (Pomacentrus partitus).
AB  - Bicolor damselfish were allowed to interact in pairs for 15 min a day during a
      five-day period. Agonistic behaviour was quantified, and at the end of the
      experimental series, concentrations of serotonin (5-HT), 5-hydroxyindoleacetic
      acid (5-HIAA) and tryptophan (TRP, the amino acid precursor of 5-HT) were
      measured, and 5-HIAA/5-HT ratios (an index of 5-HT activity) were calculated in
      the telencephalon, hypothalamus and brain stem. Socially interacting fish,
      dominant as well as subordinate, showed higher telencephalic 5-HIAA/5-HT ratios
      than isolated controls. Social interaction also decreased telencephalic TRP
      concentrations in subordinate fish but did not affect 5-HT concentrations in any
      of the brain parts. In subordinate fish, 5-HIAA/5-HT ratios in the telencephalon
      were positively correlated with the number of aggressive acts received. Moreover,
      in dominant fish 5-HIAA/5-HT ratios in the hypothalamus were positively
      correlated with the number of aggressive acts performed. These results indicate
      that the brain serotonergic system is involved in intraspecific aggression and/or
      stress reactions in bicolor damselfish.

PMID- 8886393
TI  - A morphological study of neurons expressing NADPH diaphorase activity in the
      visual cortex of the golden hamster.
AB  - The distribution of the enzyme nicotinamide adenine dinucleotide phosphate
      (NADPH) diaphorase, which is identical to nitric oxide synthase (NOS), was
      examined in cortical area 17 and the 17/18a border region in the brain of the
      golden hamster. The activity of the enzyme was present as a network of processes
      and in special populations of neurons in the visual cortex. The dense enzyme
      positive network exhibited numerous varicosities distributed throughout the
      cortex. The prominent orientation of the processes in layer I and the white
      matter are parallel to the surface of the brain, but those in layers II-IV are
      perpendicular to the surface of the brain. However, the processes in layers V and
      VI seem to run randomly. The NADPH diaphorase-positive cells could be divided
      into two classes: heavily stained neurons and lightly stained neurons. For the
      lightly stained NADPH diaphorase-positive neurons, only the cell bodies could be
      observed, whereas for the heavily stained neurons, the cell bodies and their
      varicosity-carrying dendrites and, occasionally, the smooth, thin and weakly
      stained axons were visible. The heavily stained neurons were morphologically
      diverse, but no pyramidal or spiny neurons were found. Multipolar and bipolar
      neurons were located throughout the depth of the cortex, including the white
      matter, more frequently in layers V and VI. Occasionally, monopolar neurons were
      found in layer VI. Callosal projecting neurons in the visual cortex were labeled
      retrogradely with the use of FluoSpheres applied at the opposite visual cortex,
      but these neurons did not co-localize with the NADPH diaphorase-positive neurons,
      suggesting that the callosal projecting neurons and NADPH diaphorase-positive
      neurons belong to two populations of cells in the visual cortex.

PMID- 8886394
TI  - The identification of DL-threo dihydrosphingosine and sphingosine as novel
      inhibitors of extracellular signal-regulated kinase signalling in airway smooth
      muscle.
AB  - We present entirely novel evidence that DL-threo dihydrosphingosine and
      sphingosine are inhibitors of the extracellular signal-regulated kinase (ERK)
      signalling cassette in mammalian cells. We show that DL-threo dihydrosphingosine
      is effective against both growth factor- and G-protein-dependent activation of
      ERK. We conclude that DL-threo dihydrosphingosine may represent an important
      pharmacological cell-permeable agent that may be usefully employed to block
      smooth muscle cell proliferation.

PMID- 8886395
TI  - The role of ketoconazole in the QTc interval prolonging effects of H1
      antihistamines in a guinea-pig model of arrhythmogenicity.
AB  - We have carried out experiments to re-evaluate the influence of ketoconazole (400
      mg kg-1,p.o.) on the effects of ebastine, terfenadine and loratadine on the QTc
      interval in conscious guinea-pigs. Following a previously described protocol of
      oral drug administration, but using telemetric recording of the ECG, we have
      found that the prolongation of the QTc interval attributed to ebastine and
      terfenadine is in fact entirely due to ketoconazole, and that neither
      terfenadine, ebastine nor loratadine produce any additional effects on subsequent
      administration.

PMID- 8886396
TI  - Depression of glutamatergic transmission by nociceptin in the neonatal rat
      hemisected spinal cord preparation in vitro.
AB  - The present study explored the action of nociceptin, the putative endogenous
      ligand for the orphan opioid receptor (ORL1), on the rat hemisected spinal cord
      preparation. Electrical stimulation of a dorsal root evokes a glutamatergic
      population ventral root potential (DR-VRP) in the corresponding ventral root. Low
      intensity stimulation evokes two A fibre-mediated components; a compound action
      potential of motoneurones superimposed on a population e.p.s.p. (excitatory
      postsynaptic potential); at higher stimulus intensities sufficient to activate C
      fibres a more prolonged population e.p.s.p. is evoked. All three components were
      depressed by nociceptin in a concentration-dependent manner with IC50 values
      (s.e.mean) of 119 +/- 2 nM (n = 4), 241 +/- 3 nM (n = 4) and 32 +/- 2 nM (n = 4),
      respectively. The depressant actions of nociceptin (30 nM and 300 nM) were not
      reversed by the opioid antagonist naloxone (1 microM). Nociceptin (100 nM and 300
      nM) had no effect on the afferent volleys in the dorsal root. Nociceptin
      therefore appears to be acting as an inhibitory peptide at the spinal level
      through a naloxone-insensitive opioid receptor.

PMID- 8886397
TI  - Influence of contractile agonists on the mechanism of endothelium-dependent
      relaxation in rat isolated mesenteric artery.
AB  - This study demonstrates directly that the relative contribution of nitric oxide
      (NO) and an NO synthase-independent repolarization to acetylcholine-evoked
      relaxation in rat isolated mesenteric resistance arteries is determined by the
      processes which mediate pre-contraction. Noradrenaline-induced contractions were
      reversed by acetylcholine via both NO and NO synthase-independent smooth muscle
      repolarization. In contrast, reversal of contractions to the thromboxane-mimetic,
      U46619, by acetylcholine was entirely mediated by the actions of NO,
      independently of a change in membrane potential.

PMID- 8886398
TI  - Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293
      cells.
AB  - 1. The actions of the uncompetitive N-methyl-D-aspartate (NMDA) receptor
      antagonists, memantine (1-amino-3,5-dimethyladamantane) and (+)-MK-801 ((+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate, dizocilpine),
      on recombinant NMDA receptors has been studied by use of the whole-cell patch
      clamp technique. 2. Human embryonic kidney (HEK) 293 cells were transiently
      transfected with different NMDA receptor subunit combinations (NR1a/NR2A,
      NR1a/NR2B and NR1a/NR2D). A mutant form of the green fluorescent protein (GFP)
      cotransfected with the NMDA receptor subunits to enable the visualization of
      transfected cells. 3. Memantine (0.3-30 microM) blocked L-glutamate (100 microM)
      mediated currents in a concentration-dependent manner in NR1a/NR2A, NR1a/NR2B and
      NR1a/NR2D transfected cells with IC50 values (at -70 mV) of 0.93 +/- 0.15 microM,
      0.82 +/- 0.12 microM and 0.47 +/- 0.06 microM (mean +/- s.c. mean), respectively.
      4. The memantine-induced block was strongly voltage-dependent. Alteration of the
      holding potential from -70 mV to +60 mV resulted in an e-fold increase in the
      IC50 values per 30-33 mV change in membrane potential, for all 3 subunit
      combinations investigated. 5. The kinetics of the actions of memantine (30
      microM) were investigated for the NR1a/2A combination, in 6 cells (13-15
      determinations). At -70 mV, the block and recovery from block were both best
      described by two exponentials with time-constants of 201 +/- 23 ms (81 +/- 2%)
      and 3.9 +/- 0.6 s and 597 +/- 94 ms (18 +/- 1%) and 18.6 +/- 2.4 s, respectively.
      The predominant effect of depolarization was to increase the weight of the faster
      recovery time-constant. Kinetic analysis suggests that these results are
      consistent with previously proposed Markov models. 6. (+)-MK-801 was studied
      briefly for comparative purposes. (+)-MK-801 (200 nM) preferentially blocked NMDA
      receptor currents (at -70 mV) in NR1a/NR2A and NR1a/NR2B (82 +/- 10% and 93 +/-
      2% depressions) compared to NR1a/NR2D (38 +/- 7%) transfected cells. (+)-MK-801
      appeared to be less voltage-dependent than memantine on all three receptor
      combinations. 7. In conclusion, memantine was a voltage-dependent antagonist of
      recombinant rat NMDA receptors expressed in HEK 293 cells but showed little
      selectivity between the subunits investigated. Its actions on these recombinant
      receptor combinations are similar to its actions on native NMDA receptors.

PMID- 8886399
TI  - Contrast between effects of aminobisphosphonates and non-aminobisphosphonates on
      collagen-induced arthritis in mice.
AB  - 1. Bisphosphonates (BPs) are inhibitors of bone resorption, and many derivatives
      have been developed for the treatment of enhanced bone resorption.
      Aminobisphosphonates (aminoBPs) are particularly potent in this respect. We have
      shown previously that aminoBPs, such as 4-amino-1-hydroxybutylidene-1,1
      bisphosphonic acid (AHBuBP), induce histidine decarboxylase, the enzyme forming
      histamine, and increase macrophages, granulocytes and osteoclast numbers. Non
      aminoBPs do not show this activity. 2. In the present study, an additional
      aminoBP, cycloheptyl-aminomethylene bisphosphonate (CHAMBP), was shown to have
      similar properties to AHBuBP suggesting that these actions are common among
      aminoBPs. 3. In experiments carried out to determine if aminoBPs affect immune
      responses, we found that CHAMBP and AHBuBP each exacerbated the arthritis induced
      in mice by the co-injection of type II collagen and an adjuvant, a model for
      rheumatoid arthritis. In contrast, dichloromethylene bisphosphonate (C12MBP), a
      typical non-aminoBP, did suppress the arthritis. 4. On the basis of these
      results, and those obtained previously, we propose that the exacerbating effects
      of CHAMBP and AHBuBP may be related to their ability to stimulate the synthesis
      of histamine and to increase macrophages and granulocytes. Conversely, we propose
      that the suppressive effect of C12MBP on arthritis is related to its cytotoxic
      action on macrophages or granulocytes.

PMID- 8886400
TI  - Some evidence against the involvement of arachidonic acid in muscarinic
      suppression of voltage-gated calcium channel current in guinea-pig ileal smooth
      muscle cells.
AB  - 1. To see if arachidonic acid (AA) plays a role in the sustained suppression of
      voltage-gated calcium channel currents produced by muscarinic receptor
      stimulation by carbachol (CCh), the effects of AA on membrane currents were
      examined in whole-cell voltage-clamped smooth muscle cells of the guinea-pig
      ileum. 2. In cells bathed in Ba2+ PSS and dialysed with Cs(+)-based low EGTA
      (0.05 mM) pipette solution, and in which Ba2+ current (IBa) flowing through
      voltage-gated calcium channels was evoked repeatedly by stepping to 0 mV from the
      holding potential of -60 mV, AA (1-30 microM), applied extracellularly, gradually
      suppressed IBa in a concentration-dependent manner. The IBa suppression was
      observed even with 20 mM EGTA in the pipette. 3. AA (3 microM) and CCh (10
      microM) shifted the voltage-dependent inactivation curve of IBa in the negative
      potential direction, but the effect of AA differed from that of CCh in that an
      accompanying appreciable decrease in the slope was observed. 4. The sustained
      suppression of IBa induced by CCh (10 microM) remained almost unaltered after
      pretreatment with 4-bromophenacyl bromide (10 microM), an inhibitor of
      phospholipase A2, or a combination of indomethacin (10 microM), an inhibitor of
      the cyclo-oxygenase pathway, and nordihydroguaiaretic acid (10 microM), an
      inhibitor of the lipoxygenase pathway. 5. In cells bathed in Ca2+ PSS and
      dialysed with K(+)-based pCa 6.5 pipette solution, voltage-dependent Ca2+ current
      (ICa) and K+ current (IK) were recorded simultaneously. AA (3 microM) suppressed
      IK as well as ICa, whereas CCh (10 microM) suppressed ICa but not IK. 6. We
      conclude from these results that AA or its metabolite is unlikely to be involved
      in the sustained suppression of voltage-gated calcium channel current induced by
      muscarinic receptor stimulation in guinea-pig ileal smooth muscle cells.

PMID- 8886402
TI  - Neuropeptide Y Y2 receptor-mediated attenuation of neurogenic plasma
      extravasation acting through pertussis toxin-sensitive mechanisms.
AB  - 1. The effects of neuropeptide Y (NPY) receptor agonists (administered
      intravenously) were examined on plasma protein ([125I]-bovine serum albumin)
      leakage within dura mater evoked by unilateral trigeminal ganglion stimulation
      (0.6 mA, 5 ms, 5 Hz, 5 min), capsaicin (1 mumol kg-1, i.v.) or substance P (1
      nmol kg-1, i.v.) in anaesthetized Sprague-Dawley rats. 2. NPY (EC50: 5.6 nmol kg
      1) and NPY fragment 13-36 [NPY (13-36)] (ED50: 4.3 nmol kg-1), an NPY Y2 receptor
      agonist, dose-dependently attenuated [125I]-bovine serum albumin extravasation
      from meningeal vessels when administered 10 min prior to electrical stimulation.
      [Leu31, Pro34]-NPY, an NPY Y1 and Y3 receptor agonist, inhibited the response at
      a higher dose only (23 nmol kg-1) (P < 0.05). 3. NPY also significantly decreased
      plasma protein extravasation induced by capsaicin (1 mumol kg-1) but not by
      substance P (1 nmol kg-1). 4. Pertussis toxin (20 micrograms kg-1, administered
      intracisternally 48 h prior to stimulation) blocked completely the inhibitory
      effect of NPY and NPY (13-36) but did not inhibit extravasation alone. 5. We
      conclude that NPY inhibits neurogenically-mediated plasma protein extravasation
      acting through presynaptic pertussis toxin-sensitive NPY Y2 receptors, possibly
      by inhibition of neuropeptide release from perivascular trigeminovascular
      afferents.

PMID- 8886401
TI  - PK 11195 blockade of benzodiazepine-induced inhibition of forskolin-stimulated
      adenylate cyclase activity in the striatum.
AB  - 1. The effects of benzodiazepine receptor antagonists on the inhibition of
      forskolin-stimulated adenylate cyclase (AC) activity by various benzodiazepine
      (BZ) and indoleamine agonists in the rat striatum were investigated. 2. A
      biphasic inhibition of forskolin-stimulated AC activity by the peripheral-type
      agonist, Ro5-4864, and a multiphasic inhibition by the non-selective BZ,
      diazepam, was observed. One phase of AC inhibition is consistent with a Gi
      coupled receptor-mediated action, whereas the other phases appear to involve a
      direct effect on the enzyme itself. 3. While the central-type antagonist,
      flumazenil, had no effect on the ability of Ro5-4864 to inhibit AC activity, the
      peripheral-type receptor ligand, PK 11195, abolished the first phase of
      inhibition. 4. PK 11195 and pertussis toxin were found to block the inhibitory
      effect of various BZs and the indoleamines, melatonin and 2-iodomelatonin, on
      induced AC activity. 5. Saturation binding studies, conducted at 30 degrees C
      with [3H]-diazepam revealed a single binding site in the rat striatum (KD = 19.3
      +/- 0.80 nM) which significantly decreased in affinity in the presence of GTP (KD
      = 30.5 +/- 2.6 nM; P < 0.05). No significant change in Bmax was observed. 6.
      These findings indicate the presence of Gi-coupled BZ receptors in the rat
      striatum. Thus, suppression of cyclic AMP production may contribute to the
      diverse neuropharmacological effects of BZs, melatonin and related drugs.

PMID- 8886403
TI  - Evidence of differential effects produced by ethanol on specific phospholipid
      biosynthetic pathways in rat hepatocytes.
AB  - 1. The aim of the present study was to investigate the effects of ethanol in
      vitro on the phospholipid biosynthetic pathways in hepatocytes isolated from the
      rat. We have used [methyl-14C]-choline, [1-3H]-ethanolamine and L-[3-3H]-serine
      as exogenous precursors of the corresponding phospholipids, phosphatidylcholine
      (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). 2. Incubation of
      hepatocytes in the presence of ethanol significantly alters the incorporation of
      radiolabel from [14C]-choline and [3H]-ethanolamine into the metabolic
      intermediates and the final products of the CDP-choline and CDP-ethanolamine
      pathways. Radioactivity in the metabolic intermediates of both pathways was
      significantly decreased and the amount of label in PE was reduced whilst that of
      PC was not modified. 3. In the presence of 4-methylpyrazole, an inhibitor of
      alcohol dehydrogenase (ADH) activity, ethanol produces a reduction in the label
      of choline phosphate, ethanolamine phosphate and a significant decrease in the
      amount of PC and PE radiolabel. 4. On the other hand, ethanol increases the
      incorporation of serine into phosphatidylserine, phosphatidylethanolamine and
      phosphatidylcholine, although this effect is observed only in the absence of 4
      methylpyrazole, indicating that this alteration is produced by some metabolite
      generated as a consequence of hepatic alcohol metabolism. 5. Ethanol also
      interferes with the methylation of phosphatidylethanolamine produced via the CDP
      ethanolamine pathway but it does not alter phosphatidylethanolamine methylation
      when this phospholipid is produced by mitochondrial phosphatidylserine
      decarboxylation, suggesting the existence of different intramembrane pools of
      phosphatidylethanolamine, which may exhibit different sensitivity to alcohol. 6.
      Our results indicate that ethanol exerts two different effects on phospholipid
      metabolism in hepatocytes: a stimulatory effect on the incorporation of exogenous
      substrates into different phospholipids probably related to an alteration in the
      availability of lipogenic substrates as a consequence of ethanol metabolism, and
      another inhibitory effect produced by ethanol per se, which can be observed only
      when ethanol metabolism is inhibited by the presence of a specific inhibitor of
      alcohol dehydrogenase activity.

PMID- 8886404
TI  - Renal effects of TAPP, a highly selective mu-opioid agonist.
AB  - 1. The effect of i.v. administration of TAPP, a highly selective and exclusively
      peripherally-acting mu-opioid receptor agonist, on urine output, urinary sodium,
      potassium and cyclic GMP, and on plasma immunoreactive atrial natriuretic factor
      (IR-ANF) levels was studied in conscious normally hydrated female rats (200-250
      g). 2. TAPP treatment produced a significant dose-dependent increase of urine
      output and urinary sodium, potassium and cyclic GMP excretion during the first
      hour. The highest TAPP dose used (2.5 mg kg-1. body weight) elicited a 10 fold
      elevation of urine output from 0.23 +/- 0.06 ml h-1 to 2.5 +/- 0.3 ml h-1 (n =
      18) accompanied by augmented sodium [from 17.0 +/- 4.7 mu Eq h-1 to 79 +/- 12.7
      mu Eq h-1, n = 18 (P < 0.001)], potassium [from 9.5 +/- 2.5 mu Eq h-1 to 39.4 +/-
      6.6 mu Eq h-1, n = 18 (P < 0.005)], and cyclic GMP excretion [from 191 +/- 21
      pmol h-1 to 1340 +/- 322 pmol h-1, n = 18 (P < 0.001)]. Plasma IR-ANF rose from
      22 +/- 4 pg ml-1 to 508 +/- 22 pg ml-1 (n = 18) (P < 0.001) 5 min after
      administration of TAPP (2500 micrograms kg-1). 3. TAPP lowered systemic blood
      pressure, also in a dose-related manner, 1-5 min after injection. This decrease
      in blood pressure was transient and did not last more than 10 min. 4.
      Pretreatment with the opioid antagonist naloxone (0.8 mg per rat) abolished the
      diuretic, natriuretic and kaliuretic effect of TAPP (250 micrograms kg-1); urine
      output dropped from 1.16 +/- 0.15 ml h-1, n = 12, to the control value of 0.15 +/
      0.06 ml h-1, n = 12 (P < 0.001), sodium excretion fell from 57.5 +/- 11 mu Eq h
      1, to 21.3 +/- 8.5 mu Eq h-1, n = 12 (P < 0.001), and potassium excretion
      decreased from 45.4 +/- 9.7 mu Eq h-1, n = 12, to 16.1 +/- 7.0 mu Eq h-1, (P <
      0.001). 5. Pretreatment with anti-ANF serum (0.4 ml) abolished the diuretic
      effect of TAPP: urine output diminished significantly from 1.93 +/- 0.28 to 0.88
      +/- 0.29 ml h-1 (P < 0.01) (n = 6). The TAPP-induced diuretic action, increased
      sodium/potassium excretion and elevated urinary cyclic GMP levels were also
      reversed by anti-ANF antibodies. 6. Since TAPP is totally unable to cross the
      blood-brain barrier, the ensemble of these observations led to the conclusion
      that the diuretic, natriuretic, kaliuretic and hypotensive effects produced by
      this mu-opioid agonist through interaction with peripheral mu-opioid receptors
      occur via ANF release.

PMID- 8886405
TI  - Modulation of carbachol-induced [Ca2+]i oscillations by Ca2+ influx in single
      intestinal smooth muscle cells.
AB  - 1. Oscillations of cytosolic Ca2+ concentration ([Ca2+]i) evoked by carbachol
      (CCh; 2 microM), a muscarinic agonist, were detected as oscillatory changes of
      muscarinic receptor-coupled cationic current (Icat) in guinea-pig ileal smooth
      muscle cells by the whole cell patch-clamp technique. 2. Reduction of
      extracellular Ca2+ from 2 mM to 0.2 or 0.05 mM, during CCh-induced Icat
      oscillations, caused them to disappear or to decrease markedly in frequency. A
      return to 2 mM Ca2+ concentration restored the initial Icat oscillations. 3.
      Application of nifedipine (1-3 microM) or D600 (2-5 microM) to block the voltage
      gated Ca2+ channel (VGCC) decreased the frequency of the ongoing Icat
      oscillations in the cells held at -20 mV, but it was without effect in cells held
      at -60 mV. 4. Displacement of the holding potential of -20 mV to -60 mV to
      deactivate VGCC produced a decrease, an increase or no noticeable change in the
      frequency of the Icat oscillations in different cells. Displacement to 20 mV to
      inactivate VGCC invariably produced a decrease in the frequency. In nifedipine
      treated cells, the Icat oscillations varied in frequency voltage-dependently in a
      reverse and linear way within the range -80 to 40 mV. 5. Application of
      thapsigargin (1 or 2 microM), an inhibitor of Ca(2+)-ATPase in the membrane of
      internal Ca2+ stores, caused CCh-induced Icat oscillations to disappear with a
      progressing phase during which their amplitude, but not frequency, declined. 6.
      The results suggest that membrane Ca2+ entry has a crucial role to play in
      regulation of the frequency of CCh-induced [Ca2+]i oscillations in addition to
      persistence of their generation, and that the effect is brought about by a
      potential mechanism independent of Ca2+ store replenishment. They also provide
      evidence that two types of Ca2+ permeant channels, VGCC and an as yet
      unidentified channel, are involved in the Ca2+ entry responsible for modulation
      of [Ca2+]i oscillations.

PMID- 8886406
TI  - Preferential activation of excitatory adenosine receptors at rat hippocampal and
      neuromuscular synapses by adenosine formed from released adenine nucleotides.
AB  - 1. In the present work, we investigated the action of adenosine originating from
      extracellular catabolism of adenine nucleotides, in two preparations where
      synaptic transmission is modulated by both inhibitory A1 and excitatory A(2a)
      adenosine receptors, the rat hippocampal Schaffer fibres/CA1 pyramid synapses and
      the rat innervated hemidiaphragm. 2. Endogenous adenosine tonically inhibited
      synaptic transmission, since 0.5-2 u ml-1 of adenosine deaminase increased both
      the population spike amplitude (30 +/- 4%) and field excitatory post-synaptic
      potential (f.e.p.s.p.) slope (27 +/- 4%) recorded from hippocampal slices and the
      evoked [3H]-acetylcholine ([3H]-ACh) release from the motor nerve terminals (25
      +/- 2%). 3. alpha, beta-Methylene adenosine diphosphate (AOPCP) in concentrations
      (100-200 microM) that almost completely inhibited the formation of adenosine from
      the extracellular catabolism of AMP, decreased population spike amplitude by 39
      +/- 5% and f.e.p.s.p. slope by 32 +/- 3% in hippocampal slices and [3H]-ACh
      release from motor nerve terminals by 27 +/- 3%. 4. Addition of exogenous 5'
      nucleotidase (5 u ml-1) prevented the inhibitory effect of AOPCP on population
      spike amplitude and f.e.p.s.p. slope by 43-57%, whereas the P2 antagonist,
      suramin (100 microM), did not modify the effect of AOPCP. 5. In both
      preparations, the effect of AOPCP resulted from prevention of adenosine formation
      since it was no longer evident when accumulation of extracellular adenosine was
      hindered by adenosine deaminase (0.5-2 u ml-1). The inhibitory effect of AOPCP
      was still evident when A1 receptors were blocked by 1,3-dipropyl-8
      cyclopentylxanthine (2.5-5 nM), but was abolished by the A2 antagonist, 3,7
      dimethyl-1-propargylxanthine (10 microM). 6. These results suggest that adenosine
      originating from catabolism of released adenine nucleotides preferentially
      activates excitatory A2 receptors in hippocampal CAI pyramid synapses and in
      phrenic motor nerve endings.

PMID- 8886407
TI  - Pyrimidinoceptor-mediated activation of phospholipase C and phospholipase A2 in
      RAW 264.7 macrophages.
AB  - 1. As well as the presence of P2Z purinoceptors previously found in macrophages,
      we identified pyrimidinoceptors in RAW 264.7 cells, which activate phospholipase
      C (PLC) and phospholipase A2 (PLA2). 2. The relative potency of agonists to
      stimulate inositol phosphate (IP) formation and arachidonic acid (AA) release was
      UTP = UDP > > ATP, ATP gamma S, 2MeSATP. For both signalling pathways, the EC50
      values for UTP and UDP (3 microM) were significantly lower than that for ATP and
      all other analogues tested (> 100 microM). 3. UTP and UDP displayed no additivity
      in terms of IP formation and AA release at maximally effective concentrations. 4.
      UTP-, but not ATP-, evoked AA release was 60% inhibited by pertussis toxin (PTX),
      while stimulation of IP formation by both agonists was unaffected. Short-term
      treatment with phorbol 12-myristate 13-acetate (PMA) led to a dose-dependent
      inhibition of IP responses to UTP and UDP, but failed to affect the AA responses.
      Removal of extracellular Ca2+ inhibited the PI response to UTP, but abolished its
      AA response. 5. ATP-induction of these two transmembrane signal pathways was
      decreased in high Mg(2+)-containing medium but potentiated by the removal of
      extracellular Mg2+. 6. Suramin and reactive blue displayed equal potency to
      inhibit the IP responses of UTP and ATP. 7. Both UTP and UDP (0.1-100 microM)
      induced a sustained increase in [Ca2+]i which lasted for more than 10 min. 8.
      Taken together, these results indicate that in mouse RAW 264.7 macrophages,
      pyrimidinoceptors with specificity for UTP and UDP mediate the activation of PLC
      and cytosolic (c) PLA2. The activation of PLC is via a PTX-insensitive G protein,
      whereas that of cPLA2 is via a PTX-sensitive G protein-dependent pathway. The
      sustained Ca2+ influx caused by UTP contributes to the activation of cPLA2. RAW
      264.7 cells also possess P2z purinoceptors which mediate ATP(4-)-induced PLC and
      PLA2 activation.

PMID- 8886408
TI  - Characterization of alpha 1 D-adrenoceptor subtype in rat myocardium, aorta and
      other tissues.
AB  - 1. This study was done to characterize the functional role of alpha 1D
      adrenoceptors in rat myocardium, aorta, spleen, vas deferens and prostate by use
      of the selective antagonist BMY 7378. 2. BMY 7378 inhibited [3H]-prazosin binding
      to aortic membranes with a potency (pKi 9.8 +/- 0.40) approximately 100 fold
      higher than in right ventricular membranes (pKi 7.47 +/- 0.11) and approximately
      1,000 fold higher than that in plasma membranes of the prostate (pKi 6.62 +/-
      0.39), vas deferens (pKi 6.67 +/- 0.15), salivary gland (pKi 6.46 +/- 0.38) and
      liver (6.58 +/- 0.06). 3. BMY 7378 antagonized the positive inotropic effects of
      phenylephrine (in the presence of 1 microM propranolol) on right ventricles (pA2
      7.0 +/- 0.11), left atria (pKB 7.04 +/- 0.18) and papillary muscles (pKB 6.9 +/-
      0.1) and inhibited phenylephrine-induced increase in inositol phosphates. 4. BMY
      7378 was approximately 100 fold more potent as an antagonist of phenylephrine on
      aortic strips (pA2 9.0 +/- 0.13) than on vas deferens (pKB 7.17 +/- 0.08) and
      spleen (pKB 7.16 +/- 0.21); it was ineffective on the prostate. 5.
      Chloroethylclonidine suppressed the maximal effects of phenylephrine on spleen; 5
      methylurapidil antagonized the effects of phenylephrine on aortic strips (pA2
      7.98 +/- 0.08), vas deferens (pKB 8.89 +/- 0.07) and prostate (pKB 8.85 +/-
      0.21). 6. BMY 7378 caused a dose (0.1-100 nmol kg-1)-dependent decrease in mean
      blood pressure of urethane-anaesthetized rats and its hypotensive efficacy was
      equal to that of hexamethonium. 7. The data suggest that alpha 1D-adrenoceptors
      play a significant role in rat aorta, a minor role in the heart, vas deferens and
      spleen and virtually no role in the prostate.

PMID- 8886409
TI  - Evidence for 5-HT1-like receptor-mediated vasoconstriction in human pulmonary
      artery.
AB  - 1. The 5-hydroxytryptamine (5-HT) receptors mediating contraction of human
      isolated pulmonary artery rings were investigated. Responses to the agonists 5
      carboximidotryptamine (5-CT, non-selective 5-HT1 agonist), sumatriptan (5-HT1D
      like receptor agonist), 5-HT and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH
      DPAT, 5-HT1A receptor agonist) were studied. Responses to 5-HT and sumatriptan in
      the presence of the antagonists, methiothepin (non-selective 5-HT1+2-receptor
      antagonist), ketanserin (5-HT2A receptor antagonist) and the novel antagonist,
      GR55562 (5-HT1D receptor antagonist) were also studied. 2. All agonists
      contracted human pulmonary artery ring preparations in the following order of
      potency 5-CT > 5-HT = sumatriptan > 8-OH-DPAT. Maximum responses to 5-HT, 5-CT
      and sumatriptan were not significantly different. 3. Methiothepin 1 nM and 10 nM,
      but not 0.1 nM reduced the maximum contractile responses to 5-HT but did not
      alter tissue sensitivity to 5-HT. Methiothepin 0.1 nM, 1 nM and 10 nM had a
      similar effect on responses to sumatriptan. 4. The 5-HT2A receptor antagonist
      ketanserin (10 nM, 100 nM and 1 microM) also reduced the maximum contractile
      response to both 5-HT and sumatriptan without affecting tissue sensitivity to
      these agonists. 5. The novel 5-HT1D receptor antagonist, GR55562, inhibited
      responses to 5-HT and sumatriptan in a true competitive fashion. 6. The results
      suggest that the human pulmonary artery has a functional population of 5-HT1D
      like receptors which are involved in the contractile response to 5-HT.

PMID- 8886410
TI  - The stimulation of capsaicin-sensitive neurones in a vanilloid receptor-mediated
      fashion by pungent terpenoids possessing an unsaturated 1,4-dialdehyde moiety.
AB  - 1. The irritant fungal terpenoid isovelleral caused protective eye-wiping
      movements in the rat upon intraocular instillation and showed cross-tachyphylaxis
      with capsaicin, the pungent principle in hot pepper. 2. Isovelleral induced a
      dose-dependent calcium uptake by rat dorsal root ganglion neurones cultured in
      vitro with an EC50 of 95 nM, which was fully inhibited by the competitive
      vanilloid receptor antagonist capsazepine. 3. Isovelleral inhibited specific
      binding of [3H]-resiniferatoxin (RTX), an ultrapotent capsaicin analogue, to rat
      trigeminal ganglion or spinal cord preparations with an IC50 of 5.2 microM; in
      experiments in which the concentration of [3H]-RTX was varied, isovelleral
      changed both the apparent affinity (from 16 pM to 37 pM) and the co-operativity
      index (from 2.1 to 1.5), but not the Bmax. 4. The affinity of isovelleral for
      inducing calcium uptake or inhibiting RTX binding was in very good agreement with
      the threshold dose (2.2. nmol) at which it provoked pungency on the human tongue.
      5. For a series of 14 terpenoids with an unsaturated 1,4-dialdehyde, a good
      correlation was found between pungency on the human tongue and affinity for
      vanilloid receptors on the rat spinal cord. 6. The results suggest that
      isovelleral-like compounds produce their irritant effect by interacting with
      vanilloid receptors on capsaicin-sensitive sensory neurones. Since these pungent
      diterpenes are structurally distinct from the known classes of vanilloids, these
      data provide new insights into structure-activity relations and may afford new
      opportunities for the development of drugs targeting capsaicin-sensitive
      pathways.

PMID- 8886411
TI  - Influence of parainfluenza-1 respiratory tract viral infection on endothelin
      receptor-effector systems in mouse and rat tracheal smooth muscle.
AB  - 1. In this study we have compared the effects of parainfluenza-1 respiratory
      tract viral infection on the density and function of ETA and ETB receptors in rat
      and mouse tracheal airway smooth muscle. 2. The bronchoconstrictor effect of
      inhaled methacholine was significantly enhanced in virus-infected rats, at both 4
      and 12 days post-inoculation. That is, the concentration of methacholine causing
      an increase in resistance of 100% (PC100 methacholine) was significantly lower in
      virus-infected animals at both 4 and 12 days post-inoculation (n = 6-8; P <
      0.05). 3. Total specific binding of [125I]-endothelin-1 and the relative
      proportions of ETA and ETB binding sites for [125I]-endothelin-1 were assessed in
      tracheal airway smooth muscle in parainfluenza-1-infected rats and mice at days
      2, 4 and 12 post-inoculation using the ligands BQ-123 (1 microM; ETA receptor
      selective) and sarafotoxin S6c (100 nM; ETB receptor-selective). Total specific
      binding in mice was significantly reduced at day 2 post-inoculation (n = 5; P <
      0.05) but not at days 4 and 12 post-inoculation (n = 5). In control mice, the
      proportions of ETA and ETB binding sites were 53%:47% at day 2 and 43%:57% at day
      4 and these were significantly altered by parainfluenza-1 infection such that,
      the ratios were 81%:19% at day 2 and 89%:11% at day 4 (P < 0.05). By day 12 post
      inoculation, the proportion of ETA and ETB binding sites in tracheal smooth
      muscle from mice infected with parainfluenza-1 was not significantly different
      from control. In rat tracheal airway smooth muscle, neither total specific
      binding nor the ETA and ETB binding site ratio (64%:36%) were significantly
      altered in virus-inoculated rats at days 2, 4 or 12 post-inoculation (n = 5). 4.
      Parainfluenza-1 infection in mice had no effect on the sensitivity or maximal
      contractile effect of endothelin-1 in tracheal smooth muscle at days 2, 4 or 12
      post-inoculation (n = 4). In contrast, contraction in response to the ETB
      receptor-selective agonist sarafotoxin S6c was attenuated by 39% at day 2 and by
      93% at day 4 post-inoculation (P < 0.05). However, by day 12 post-inoculation,
      contractions to sarafotoxin S6c were not significantly different between control
      and virus-infected mice. In parainfluenza-1-infected rats, there were small but
      significant reductions in the sensitivity to carbachol, endothelin-1 and
      sarafotoxin S6c whilst the maximal responses to the highest concentrations of
      these agonists were not significantly altered by virus infection (n = 8). 5. BQ
      123 (3 microM) had no significant effect on cumulative concentration-effect
      curves to endothelin-1 in tracheal preparations from control mice (n = 4) or
      parainfluenza-1-infected rats (n = 8). In contrast, in tissues taken from virus
      infected mice at day 4 post-inoculation, BQ-123 caused a marked 9.6 fold
      rightward shift in the concentration-effect curve to endothelin-1 (n = 4). 6. In
      summary, we have demonstrated that parainfluenza-1 infection in mice transiently
      reduced the density of tracheal airway smooth muscle ETB receptors and this was
      reflected in reduced responsiveness to the ETB receptor-selective agonist
      sarafotoxin S6c. In contrast, whilst parainfluenza-1 infection in rats was
      associated with the pathological features and bronchial hyperresponsiveness
      common to respiratory tract viral infection, there was no selective down
      regulation of ETB receptor expression or functional activity. The reasons for
      these species differences are not clear, but may relate to differences in the
      airway inflammatory response to parainfluenza-1 virus.

PMID- 8886412
TI  - Mediation by neurotensin-receptors of effects of neurotensin on self-stimulation
      of the medial prefrontal cortex.
AB  - 1 Intracortical microinjections of neurotensin (NT) selectively decreased
      intracranial self-stimulation (ICSS) of the medial prefrontal cortex in the rat.
      2 To elucidate whether this effect is mediated by NT receptors or by the
      formation of NT-dopamine complexes, we investigated the effects on ICSS of
      intracortical microinjections of neurotensin (1-11), an NT fragment that forms
      extracellular complexes with dopamine but does not bind to NT receptors. 3 We
      also studied the effects of the peripheral administration of SR 48692, a
      selective antagonist of NT receptors, on the inhibition of ICSS produced by the
      intracortical administration of NT. 4 Unilateral microinjections of neurotensin
      (1-11) at doses of 10, 20 and 40 nmol into the medial prefrontal cortex did not
      change the basal ICSS rate of this area. 5 The intraperitoneal administration of
      SR 48692 at doses of 0.08 and 0.16 mg kg-1 30 min before microinjection of 10
      nmol of NT into the medial prefrontal cortex, antagonized the inhibition of ICSS
      produced by the neuropeptide. 6 These results demonstrate that the inhibitory
      effect of NT on ICSS is mediated by NT receptors.

PMID- 8886413
TI  - Pharmacological characterization of the 5-hydroxytryptamine receptor mediating
      relaxation in the rat isolated ileum.
AB  - 1 The aim of the present study was to investigate a 5-HT4 receptor involvement in
      the mediation of a 5-HT-induced relaxation response in the rat isolated ileum in
      vitro. 2 Ileal segments were taken at regular intervals from the ileo-caecal
      junction to duodenum. 5-HT (1 microM) induced a relaxation or contraction
      response in segments taken from the terminal ileum: the relaxation decreased and
      finally disappeared as contractions dominated in the proximal tissues. The 5-HT
      induced relaxations were enhanced in the terminal segments and the contractions
      attenuated in both terminal and proximal segments, in the presence of
      methysergide (1 microM) and atropine (0.1 microM). 3 In the presence of
      methysergide (1 microM) and atropine (0.1 microM), a cumulative addition of 5-HT
      (0.01-1 microM) induced a concentration-dependent relaxation in the terminal (1
      20 cm from the ileo-ceacal junction) ileal segments which at higher
      concentrations of 5-HT (3-30 microM) reverted to contraction. 4 The rank order of
      potency of indole agonists in inducing a concentration-related relaxation
      response in tissues of the terminal ileum (pretreated with pargyline (100 microM)
      and in the presence of methysergide (1 or 100 microM) and atropine (0.1 microM)
      was 5-hydroxytryptamine (6.97 +/- 0.06), 5-methoxytryptamine (6.50 +/- 0.07),
      alpha-methyl-5-hydroxytryptamine (5.53 +/- 0.17), 5-carboxamidotryptamine (5.51
      +/- 0.12) and 2-methyl-5-hydroxytryptamine (< 5), the pEC50 values (mean +/-
      s.e.mean) being shown in parentheses. 5 Pretreatment of tissues with pargyline
      (100 microM) selectively enhanced the potency of 5-methoxytryptamine by a factor
      of 19 but failed to modify the potency of the other indole agonists. 6 The 5-HT4
      receptor antagonists, tropisetron, SDZ 205-557 and GR 113808 antagonized the
      relaxation response to 5-HT (in the presence of methysergide (1 or 10 microM) and
      atropine (0.1 microM)) with pKB values (95% CL) of 6.09 (5.94-6.24), 7.0 (6.9
      7.09) and 8.95 (8.81-9.1) respectively. Apparent pKB values estimations for
      tropisetron (1 microM) and GR 113808 (10 nM) using the agonists 5
      methoxytryptamine and 5-carboxamidotryptamine were 6.37 +/- 0.31, 5.91 +/- 0.38
      and 8.83 +/- 0.11, 8.82 +/- 0.22 respectively. 7 Tropisetron (10 microM), SDZ 205
      557 (3 microM) and GR 113808 (10-100 nM) caused an increase in basal tone of the
      rat terminal ileum when administered in the presence of methysergide and
      atropine. 8 The relaxation response to 5-HT in the rat terminal ileum was not
      antagonized by ritanserin (1 microM), ondansetron (1 microM) or N omega-nitro-L
      arginine methyl ester (100 microM) and with only a twofold dextral shift of the
      concentration-response curve by tetrodotoxin (1 microM). 9 It is concluded that
      the relaxant response to 5-HT in the terminal region of the ileum is mediated
      directly at the smooth muscle; a ranked indole agonist potency and selective
      antagonism by 5-HT4 receptor antagonists tropisetron, SDZ 205-557 and GR 113808
      indicate a 5-HT4 receptor involvement in the relaxation response.

PMID- 8886414
TI  - The increase in human plasma immunoreactive endothelin but not big endothelin-1
      or its C-terminal fragment induced by systemic administration of the endothelin
      antagonist TAK-044.
AB  - 1. We examined the effects of systemic infusion, in healthy human volunteers, of
      the endothelin antagonist TAK-044 on the plasma concentrations of mature
      endothelin, big endothelin-1 and the C-terminal fragment of big endothelin-1, by
      selective solid-phase extraction and specific radioimmunoassays. 2. Unlabelled
      TAK-044 competed with specific [125I]-endothelin-1 binding to human left
      ventricle tissue in a biphasic manner giving KD values of 0.11 nM and 26.8 nM at
      the ETA and ETB receptor subtypes, respectively, indicating a 244 fold
      selectivity for the ETA receptor subtype. 3. A 15 min intravenous infusion of
      placebo or 30 mg TAK-044 (giving a serum concentration of 2 nM, calculated to
      block > 95% of ETA but < 5% ETB receptors) had no effect on the immunoreactive
      plasma concentrations of the three peptides. 4. At the higher dose of 750 mg TAK
      044 (giving a serum concentration of 80 nM, calculated to block > 99% of ETA and
      > 75% ETB receptors), the immunoreactive plasma endothelin concentrations were
      increased 3.3 fold over basal levels (P < 0.01). The concentrations of big
      endothelin-1 or C-terminal fragment of big endothelin-1 were unchanged. 5. At
      both doses of TAK-044, there were significant decreases in diastolic blood
      pressure, and peripheral vascular resistance, with corresponding increases in
      cardiac index and stroke index. There were no changes in systolic or mean
      arterial blood pressures or heart rate. 6. Since only the concentrations of the
      mature peptide were increased, we conclude that the most likely sources of
      endothelin contributing to the observed rise were displacement of receptor-bound
      peptide and reduction in plasma clearance rather than peptide synthesis.

PMID- 8886415
TI  - Inhibition of Ca(2+)-sensitive K+ currents in NG 108-15 cells by substance P and
      related tachykinins.
AB  - 1. The whole-cell patch-clamp technique was used to investigate the actions of
      substance P and other agonists at neurokinin (NK) receptors on voltage-gated K+
      and Ca+ channel currents in undifferentiated mouse neuroblastoma x rat glioma NG
      108-15 cells. 2. Both substance P (0.3-30 microM) and the NK1 receptor selective
      agonist GR73632 (10 nM-10 microM) caused concentration-dependent inhibition of K+
      currents. GR64349 and senktide (agonists at NK2 and NK3 receptors respectively)
      also inhibited K+ currents, but only at concentrations which were several orders
      of magnitude greater than GR73632, suggesting that current inhibition was
      mediated via NK1 receptors. 3. Substance P and GR73632 were without effect on
      residual K+ currents recorded in the presence of extracellular Co2+ (4 mM) to
      abolish the Ca(2+)-sensitive component (IKca) of the K+ current. Ca2+ channel
      currents, recorded with either Ba2+ or Ca2+ as charge carrier, were unaffected by
      NK1, NK2 and NK3 receptor ligands. 4. Iontophoretic application of GR73632
      produced a current-dependent reduction of K+ currents. In the presence of the non
      peptide NK1 antagonists, CP-99,994 and RP67580, and the peptide antagonist,
      GR82334, the current-response relationship was reversibly shifted to the right.
      This indicates that the response is mediated by NK1 receptors. 5. Our results
      indicate that activation of NK1 receptors leads to the selective inhibition of
      IKca in undifferentiated NG 108-15 cells.

PMID- 8886417
TI  - Endothelial 5-HT receptors mediate relaxation of porcine pulmonary arteries in
      response to ergotamine and dihydroergotamine.
AB  - 1. The aim of the present study was to investigate whether antimigraine ergot
      compounds may act at endothelial 5-hydroxytryptamine (5-HT) receptors which
      trigger the release of endothelium-derived relaxing factor (EDRF). Changes in
      tone of porcine isolated pulmonary arteries were measured isometrically. The
      integrity of the endothelium was assessed by the bradykinin-induced relaxation of
      prostaglandin F2 alpha (PGF2 alpha, 3 microM)-precontracted vessels. 2. The ergot
      derivatives ergotamine, dihydroergotamine (DHE) and dihydroergocristine, as well
      as 5-HT and (+/-)-alpha-methyl-5-HT, elicited a reversible endothelium-dependent
      relaxation of PGF2 alpha-precontracted arterial ring segments. The relaxation to
      both ergotamine and 5-HT was associated with an increase in cyclic GMP. After
      pretreatment of the vessels with NG-nitro-L-arginine methyl ester (200 microM),
      or removal of endothelium by mechanical rubbing, the relaxant responses were
      abolished. 3. The mean pEC50 values for relaxant responses followed the order:
      (+/-)-alpha-methyl-5-HT (8.80) > 5-HT (8.75) > ergotamine (8.17) > DHE (7.70) > 5
      carboxamidotryptamine (7.62) > dihydroergocristine (7.17). 4. The relaxant
      effects of both ergotamine and dihydroergotamine were resistant to block by
      indomethacin (3 microM), prazosin (1 microM) and ketanserin (1 microM). However,
      the ergotamine-induced relaxation was highly susceptible to block by pizotifen
      (pA2 = 8.23), norclozapine (pA2 = 8.20), methiothepin (-log IC50 = 7.26),
      rauwolscine (pA2 = 7.24) and mesulergine (pA2 = 6.64). Each antagonist inhibited
      the relaxant responses to (+/-)-alpha-methyl-5-HT in the same manner with similar
      potency as that determined against ergotamine. 5. Recently, mRNA transcripts for
      5-HT1D beta and 5-HT2B receptors have been demonstrated in porcine pulmonary
      arteries. The rank order of potencies of agonists and antagonists in the present
      study suggests that the relaxant responses to 5-HT and ergot derivatives are
      mediated through activation of endothelial 5-HT receptors which are similar to
      the 5-HT2B receptor subtypes.

PMID- 8886416
TI  - The functional investigation of a human adenocarcinoma cell line, stably
      transfected with the neuropeptide Y Y1 receptor.
AB  - 1. The human adenocarcinoma cell line, HT-29, has been stably transfected with
      the cDNA sequence for the rat neuropeptide Y (NPY) Y1 receptor, and three Y1
      clones (Y1-4, Y1-7 and Y1-16) have been isolated which express high levels of
      specific [125I]-PYY binding. We have studied the functional responses or lack of
      responses to peptide YY (PYY) and its analogues in the three transfected clones
      and HT-29 wild type (wt) cells. 2. Vasoactive intestinal polypeptide (VIP)
      produced long-lasting increases in short-circuit current (SCC) in both HT-29 wt
      cells and the Y1 clones. VIP EC50 values were 8.4-11.7 nM in all four cases. The
      elevation in SCC after a maximal concentration of VIP (30 nM) was significantly
      greater in Y1-7 cells than in either HT-29 wt epithelia or the other Y1 cell
      lines. 3. PYY (100 nM) and human pancreatic polypeptide (hPP; 1 microM) were
      ineffective in HT-29 wt cells under either basal or stimulated conditions. In
      contrast, basolateral additions of PYY reduced both basal and VIP-stimulated SCC
      in all three Y1 clones. After VIP, the PYY EC50 values (in nM) were 18.6 in Y1-4,
      8.0 in Y1-7 and 52.5 in Y1-16 hPP (1 microM) produced only small and transient
      responses in each transfected cell type. 4. The Y1 receptor agonist, [Leu31,
      Pro34] NPY (1 microM) was also effective in the three Y1 cell lines. In the Y1-7
      clone the EC50 value for the effect of this peptide was 149 nM, 18.6 fold less
      potent than PYY. 5. PYY and the Y1-selective non-peptide antagonist, BIBP 3226
      displaced [125I]-PYY binding from Y1-7 cell membranes with Ki values of 2.0 and
      3.1 nM respectively. In the Y1-7 clone, BIBP 3226 fully inhibited the reductions
      in VIP-stimulated SCC induced by 30 nM PYY, with an IC50 of 27.2 nM and 30 nM
      BIBP 3226 caused a parallel rightward shift on the PYY concentration-response
      curve, with an approximate pKB of 8.0. 6. HT-29 clones stably expressing the Y1
      receptor therefore show responses to PYY and its analogues that are
      characteristic of that subtype, and the Y1-7 clone in particular will be useful
      in the assessment of novel Y1-specific drugs. This approach will also allow the
      functional study of NPY Yi receptors with selected mutations.

PMID- 8886418
TI  - Activation of cardiac chloride conductance by the tyrosine kinase inhibitor,
      genistein.
AB  - 1. Genistein (GST), an inhibitor of protein tyrosine kinase (PTK), Na3VO4 (VO4),
      an inhibitor of phosphotyrosine phosphatase (PTPase), and forskolin (FSK), an
      activator of the cyclic AMP-dependent, cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl- channel, were applied to guinea-pig ventricular myocytes to
      probe for a possible role of tyrosine phosphorylation in the regulation of
      cardiac Cl- channels. 2. Myocytes in the standard whole-cell configuration were
      pulsed to various potentials and Cl- current (ICl) measured as the difference
      from control background current. GST (1-500 microM) activated a current that had
      similar biophysical properties (time- and voltage-independent; Cl(-)-dependent
      reversal potential and outward rectification) as ICl activated by 5 microM FSK.
      The EC50 for activation of Cl- conductance (gCl) by GST was approximately 100
      microM, and gCl activated by GST (500 microM) was as large as gCl activated by
      maximally-effective FSK (5 microM). Daidzein, a GST analogue with little effect
      on PTK, was at least one order less effective than GST. 3. GST responses were
      rapidly and reversibly inhibited by 0.1-1 mM VO4 treatments that had little
      effect on FSK-activated ICl. 4. Niflumic acid (100-200 microM) reversibly
      depressed GST (100 microM)-activated gCl by 55%. 5. GST (50 microM) strongly
      incremented current in myocytes with cyclic AMP-dependent CFTR ICl already
      activated by maximally-effective FSK 5 microM. 6. Based on these results, and on
      evidence of a synergistic interaction between GST and FSK, we conclude that
      inhibition of tyrosine phosphorylation by GST causes an activation of cardiac
      CFTR that is not mediated by an elevation of cyclic AMP.

PMID- 8886419
TI  - Attenuation by prolonged nitric oxide synthase inhibition of the enhancement of
      fibrinolysis caused by environmental stress in the rat.
AB  - 1. Nitric oxide (NO) suppresses platelet aggregation and plasminogen activator
      inhibitor (PAI) release from platelets, playing physiological and/or pathological
      roles in the haemostatic system. We investigated the effect of NG-nitro-L
      arginine methyl ester (L-NAME), an NO synthase inhibitor, on the disseminated
      intravascular coagulation (DIC)-like phenomena in rats under environmental
      stress, induced by prolonged fluctuation in air temperature, known as SART
      (specific alternation of rhythm in temperature) stress. 2. Exposure of rats to
      SART stress for 7 days caused mild DIC-like symptoms such as thrombocytopenia,
      hypofibrinogenemia, decreased factor VIII: coagulant activity and shortened
      euglobulin clot lysis time (ECLT). The enhanced fibrinolysis was accompanied by a
      marked decrease in the activity of plasma PAI. 3. L-NAME, but not its D
      enantiomer, when administered orally at 0.3-10 mg kg-1, twice a day for 7-day
      exposure to stress, inhibited the stress-induced decrease in fibrinogen levels in
      a dose-dependent manner, whereas it failed to alter platelet count, factor
      VIII:coagulant activity and plasma protein levels in stressed rats. All these
      parameters in unstressed rats were resistant to L-NAME at 10 mg kg-1. 4. Repeated
      treatment with 10 mg kg-1 of L-NAME blocked the shortening of ECLT and the
      decrease in PAI activity following stress exposure, although it was without
      effect in unstressed rats. 5. The inhibitory effects of L-NAME at 10 mg kg-1 on
      the stress-induced alterations in fibrinogen levels and in ECLT were
      significantly reduced by coadministered L-arginine at 1000 mg kg-1. 6. These
      findings demonstrate that repeated administration of L-NAME attenuates the
      enhanced fibrinolysis, without aggravating thrombocytopenia, in SART-stressed
      rats. Endogenous NO appears to contribute to the stress-induced development of
      fibrinolysis by suppressing, plasma PAI activity, most probably as a result of
      inhibition of the PAI release from platelets.

PMID- 8886420
TI  - Interleukin-8 production by the human colon epithelial cell line HT-29:
      modulation by interleukin-13.
AB  - 1. We have determined which cytokines induce and modulate the production of the
      chemokine interleukin-8 (IL-8) by the human colonic epithelial cell line HT-29.
      2. Growth arrested cell cultures were stimulated with the human recombinant
      cytokines interleukin-1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF
      alpha), interferon-gamma (IFN-gamma), interleukin-13 (IL-13), interleukin-10 (IL
      10) or vehicle added alone or in combination. The production of IL-8 was
      determined by enzyme-linked immunosorbent assay (ELISA) and IL-8 messenger RNA
      expression by Northern blot analysis. 3. The production of IL-8 in unstimulated
      cells was undetectable by both ELISA and Northern blot analysis. 4. HT-29 cells
      produced IL-8 following stimulation with IL-1 alpha or TNF-alpha in a time- and a
      concentration-dependent manner, while IFN-gamma, IL-10 and IL-13 did not induce
      IL-8 production by HT-29 cells. 5. IL-13 was found to up-regulate significantly
      (P < 0.01) the IL-1 alpha but not the TNF-alpha-induced IL-8 generation by HT-29
      cells. In contrast, IL-10 had no effect on either IL-1 alpha or TNF-alpha-induced
      IL-8 production. 6. Experiments using cycloheximide demonstrated that this
      synergistic effect of IL-13 and IL-1 alpha on IL-8 secretion was not through de
      novo protein synthesis. Using actinomycin-D, we demonstrated that the IL-13 up
      regulation was at the level of transcription rather than messenger RNA stability.
      7. These findings suggest that colonic epithelial cells have a functional IL-13
      receptor, which is coupled to an up-regulation of IL-1 alpha, but not TNF-alpha
      induced IL-8 generation.

PMID- 8886421
TI  - The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced
      intracellular calcium mobilization.
AB  - 1. Brain capillary endothelial cells responded to uridine 5'-triphosphate (UTP)
      and adenosine 5'-triphosphate (ATP) by activation of phospholipase C and by large
      changes in [Ca2+]i. These cells expressed mRNA sequences identical to the
      sequence of the P2Y2-purinoceptor of rat pituitaries. 2. Pyridoxalphosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS) at 100 microM did not prevent UTP and
      ATP induced accumulations of total [3H]-inositol (poly)phosphates. It inhibited
      UTP and ATP induced intracellular Ca2+ mobilization (IC50 = 30 microM) by non
      competitive mechanism. 3. PPADS (100 microM) inhibited endothelin-1 induced
      accumulation of total [3H]-inositol (poly)phosphates by less than 20% and
      prevented most of endothelin-1 induced intracellular Ca2+ mobilization (IC50 = 30
      microM). 4. PPADS (100 microM) had no action on ionomycin induced intracellular
      Ca2+ mobilization. 5. Microinjection of inositol (1,4,5)trisphosphate (InsP3)
      into Xenopus oocytes induced large Ca2+ activated Cl- currents that were
      prevented by heparin and by PPADS. 6. It is concluded that PPADS does not
      recognize rat P2Y2-purinoceptors and prevents UTP and ATP induced intracellular
      Ca2+ mobilization by a non-specific mechanism that could involve the inhibition
      of InsP3 channels.

PMID- 8886422
TI  - Role of bradykinin receptors in the renal effects of inhibition of angiotensin
      converting enzyme and endopeptidases 24.11 and 24.15 in conscious rabbits.
AB  - 1. We tested the effects on systemic haemodynamics and renal function, of
      inhibition of endopeptidase (EP) 24.15 (E.C. 3.4.24.15), in conscious
      uninephrectomized rabbits in which the activities of angiotensin converting
      enzyme (ACE, E.C. 3.4.15.1) and neutral endopeptidase (EP 24.11, E.C. 3.4.24.11)
      were already inhibited. To test the role of bradykinin B2-receptors in mediating
      the effects following inhibition of these enzymes, the antagonist Hoe 140 was
      used. 2. Hoe 140 (0.1 mg kg-1, i.v.) did not affect resting mean arterial
      pressure or heart rate, but antagonized the depressor effect of right atrial
      administration of bradykinin. The dose-response curve for bradykinin was shifted
      more than 1000 fold to the right for more than 4 h. Hoe 140 approximately doubled
      resting urine flow and increased fractional Na+ excretion from 4.2 to 6.0%;
      consistent with the hypothesis that it exerts a partial agonist effect on the
      kidney. 3. Combined inhibition of ACE (captopril; 0.25 mg kg-1 plus 0.2 mg kg-1h
      1) and EP 24.11 (SCH 39370; 3 mg kg-1 plus 3 mg kg-1h-1) was followed by a
      sustained reduction in arterial pressure (-6 +/- 2 mmHg) and increase in heart
      rate (35 +/- 7 beats min-1). There was a small increase in renal blood flow (by
      6.5 +/- 3.2% relative to vehicle-treatment) without a change in glomerular
      filtration rate, and about a 150% increase in Na+ excretion. Hoe 140 (0.1 mg kg
      1, i.v.) pretreatment did not influence the renal effects of captopril and SCH
      39370, although it did appear to blunt their hypotensive and tachycardic effects.
      4. When EP 24.15 was inhibited with N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala
      Tyr-p-aminobenzoate (cFP-AAY-pAB; 5 mg kg-1 plus 3 mg kg-1h-1, i.v.) in rabbits
      pretreated with captopril and SCH 39370, no changes in systemic haemodynamics or
      renal function were observed. 5. We concluded that in conscious uninephrectomized
      rabbits, EP 24.15 does not play a major role in modulating renal function, at
      least under conditions where ACE and EP 24.11 are already inhibited. In contrast,
      ACE and/or EP 24.11 do modulate renal function in this model, but their
      influences are mediated chiefly through metabolism of peptides other than
      bradykinin.

PMID- 8886423
TI  - Evidence for mediation of L-2-chloropropionic acid-induced delayed neuronal cell
      death by activation of a constitutive nitric oxide synthase.
AB  - 1. Delayed neuronal cell death elicited by excess excitatory amino acid
      concentrations has been strongly implicated in many neurological disorders
      including head trauma, stroke, motor neurone disease and Huntington's disease. We
      have used the neurotoxin, L-2-chloropropionic acid (L-CPA) to model cellular
      events in vivo leading to delayed neuronal cell loss which is confined to the
      cerebellar cortex and can be prevented by inhibitors of nitric oxide synthase
      such as NG-nitro-L-arginine methyl ester. 2. Experiments were performed to
      determine whether the constitutive nitric oxide synthase (NOS) or inducible form
      of NOS (iNOS) was responsible for the neuronal cell death. Activation of NOS was
      confirmed by a 39% increase in cerebellar total nitrate and nitrite
      concentrations in L-CPA-treated brains, as compared to controls (controls = 2.53
      +/- 0.10; L-CPA treated = 3.51 +/- 0.31 nmol mg-1 protein, P < 0.01 Student's t
      tests, n = 6, mean +/- s.e.mean). Biochemical measurements of total NOS activity
      were made in homogenates of cerebellum 6 h and 48 h following L-CPA
      administration, times at which L-CPA concentrations are maximal in brain and a
      time when there is a high proportion of cerebellar granule cell death,
      respectively. NOS activity as measured by the amount of [3H]-arginine converted
      to [3H]-citrulline, did not reveal any difference between controls (rats dosed
      with water) and animals dosed with L-CPA at either 6 or 48 h following dosing.
      Furthermore the ability of three NOS inhibitors, NG-nitro-L-arginine, 7-bromo-3
      nitroindazole and S-methylisothiourea to block the conversion of [3H]-citrulline
      to [3H]-arginine was identical at 6 and 48 h time points in control and L-CPA
      treated rats. 3. Quantitative autoradiography using [3H]-NG-nitro-L-arginine was
      used to measure the relative anatomical distribution and amount of NOS enzyme in
      the cerebellum of controls and L-CPA-treated rats 48 h following dosing. There
      was no significant alteration in the binding of [3H]-NG-nitro-L-arginine to
      granular and molecular layers of the cerebellum of control and L-CPA-treated rat
      brains. 4. Western blotting using antibodies against the inducible NOS enzyme
      failed to detect the protein in cerebellums of L-CPA-treated rats when measured
      48 h after L-CPA dosing. 5. In conclusion, the increase in cerebellar
      nitrate/nitrite concentrations in L-CPA-treated rats provides further evidence
      for activation of NOS in the cerebellum following administration of L-CPA. The
      failure to demonstrate an increase in NOS activity at 6 or 48 h in L-CPA-treated
      rats as compared to controls suggests that the source of nitric oxide responsible
      for the granule cell death must originate from the constitutive NOS enzyme,
      probably the neuronal form which is highly enriched in the cerebellum. This
      hypothesis was further substantiated by Western blotting and quantitative
      autoradiography.

PMID- 8886424
TI  - Analogues of diverse structure are unable to differentiate native melatonin
      receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.
AB  - 1. The pineal hormone melatonin exerts its biological effects through specific,
      high affinity G-protein coupled receptors. Recently, three melatonin receptor
      subtypes (Mel1a, Mel1b and Mel1c) have been cloned. Neither the cloned subtypes,
      nor the native receptors have yet been compared in a detailed pharmacological
      analysis. 2. The present study examined the structure-activity relationships of a
      series of 21 melatonin analogues, by comparing their potency on the pigment
      aggregation response in Xenopus laevis melanophores with their affinity in
      radioligand binding competition studies in chicken retina and sheep pars
      tuberalis (PT), two tissues in which melatonin is known to mediate a biological
      response. 3. All but four of the analogues were full melatonin receptor agonists
      producing a concentration-related redistribution of pigment granules in cultured
      Xenopus melanophores. The remaining analogues produced little pigment aggregation
      at 10 microM. 4. Saturation studies with 2-[125I]-iodomelatonin identified a
      single binding site in the chicken retina and sheep PT membranes, with a KD of
      36.6 +/- 2.8 and 37.3 +/- 4.3 pM, and a maximal number of binding sites (Bmax) of
      16.6 +/- 0.5, and 40.1 +/- 1.7 fmol mg-1 protein, respectively. 5. Comparison of
      the potency/affinity of the analogues for the binding sites gave a highly
      significant correlation in each case, retina/melanophore, r = 0.97 (P < 0.001, n
      = 17), PT/melanophore, r = 0.97 (P < 0.001, n = 17) and PT/retina, r = 0.98 (P <
      0.001, n = 21). 6. Despite their large range in affinity and structural diversity
      these melatonin agonists were unable to distinguish between melatonin receptors
      in the chicken retina, sheep pars tuberalis and Xenopus melanophores.

PMID- 8886425
TI  - Interactions between nitric oxide and prostanoids in isolated perfused kidneys of
      the rat.
AB  - 1. The present study was aimed to assess the interaction between nitric oxide
      (NO) and thromboxane (Tx) A2-prostaglandin (PG) H2 in single-pass perfused
      isolated kidneys of the rat. 2. Noradrenaline (NA, 63 and 110 nM) dose
      dependently elevated the renal vascular resistance (RVR), the glomerular
      filtration rate (GFR) and the urinary excretion of sodium (UNa V). Infusion of N
      omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), an inhibitor of NO
      synthesis, enhanced the effects of NA on RVR and on UNa V, but decreased those on
      GFR. The TxA2-PGH2 (TP) receptor blockade by GR32191B (10 microM) attenuated this
      potentiating effect of L-NAME. 3. When renal perfusion pressure was stepwise
      increased from 90 to 150 mmHg, L-NAME similarly decreased renal perfusion flow
      rate and GFR. 4. The venous excretion of TxB2 and 6-keto-PGF1 alpha was increased
      by L-NAME in baseline conditions as well as after NA or increasing renal
      perfusion pressure (RPP). 5. These results suggest that: (1) TxA2 and PGH2 play
      an important role in the overall effect of the renal prostanoids, (2) NO strongly
      interacts with the cyclo-oxygenase pathway and reduces the prostanoid synthesis
      in the kidney, and (3) the pressor effect of L-NAME partly relies upon the
      vasoconstrictor effect of TxA2 and PGH2.

PMID- 8886426
TI  - Comparison of angiotensin II type 1 receptor blockade and angiotensin-converting
      enzyme inhibition in pregnant sheep during late gestation.
AB  - 1. The effects of antagonism of the maternal renin-angiotensin system (RAS) with
      either an angiotensin II type 1-(AT1) specific receptor blocker (GR138950) or an
      angiotensin-converting enzyme (ACE) inhibitor (captopril) were compared in
      chronically-catheterised ewes and their foetuses during late gestation. 2. Daily
      from 127 +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe
      received i.v. either GR138950 (3 mg kg-1; n = 10), captopril (3 mg kg-1; n = 6)
      or an equivalent volume of vehicle solution (0.9% w/v saline; n = 10). 3. Within
      2 h of drug administration, GR138950 abolished the maternal, but not the foetal,
      pressor responses to angiotensin II (AII; 100-188 ng kg-1, i.v.; P < 0.05),
      whereas captopril abolished both the maternal and foetal pressor responses to
      angiotensin I (AI; 400-750 ng kg-1, i.v.; P < 0.05). 4. On the first day of
      treatment, maternal blood pressure decreased in all GR138950-treated (-21 +/- 4
      mmHg; P < 0.05) and captopril-treated (-13 +/- 5 mmHg; P > 0.05) ewes at 2 h
      after drug administration. Captopril also significantly decreased foetal blood
      pressure by 5 +/- 1 mmHg (P < 0.05). However, foetal blood pressure in the
      GR138950-treated animals remained unchanged. Maternal and foetal heart rates were
      unaffected by any treatment. Uterine blood flow was significantly reduced within
      2 h of both GR138950 (-130 +/- 20 ml min-1; P < 0.05) and captopril (-72 +/- 16
      ml min-1; P < 0.05) administration. 5. On the first day of treatment, maternal
      arterial haemoglobin (Hb) concentration and oxygen (O2) content increased at 2 h
      in all GR138950-treated and captopril-treated ewes. Foetal arterial pH and
      oxygenation (O2 content, O2 saturation and Pao2) were reduced by a similar extent
      in both groups of drug-treated ewes. 6. After one week of daily GR138950
      administration, maternal blood pressure decreased from a pretreatment value of 96
      +/- 5 mmHg on day 1 to 79 +/- 2 mmHg by day 7 (P < 0.05). Captopril treatment had
      no long-term effect on maternal blood pressure. Although foetal blood pressure
      increased by 3 +/- 1 mmHg over a week of vehicle treatment (P < 0.05), no
      significant differences were observed between the long-term changes in foetal
      blood pressure in all three groups of animals. 7. There were no long-term effects
      of drug administration on maternal Hb concentration or oxygenation, or on the
      foetal haematological parameters. However, changes in maternal PaCo2 observed in
      the GR138950-treated (+1.4 +/- 0.5 mmHg; P < 0.05) and captopril-treated (+3.3 +/
      1.1 mmHg; P > 0.05) ewes were significantly different from those seen in the
      vehicle-treated animals (P < 0.05). 8. There were no apparent adverse effects of
      maternal GR138950 or captopril treatment on foetal viability. 9. The present
      study demonstrated that administration of either GR138950 or captopril to
      pregnant ewes effectively blocked the maternal RAS, and caused hypotension and a
      decrease in uterine blood flow. However, only captopril appeared to cross the
      placenta to influence directly the RAS of the sheep foetus. This suggests that
      the fall in foetal oxygenation observed after AT1-specific receptor blockade and
      ACE inhibition originates primarily from changes in the maternal and/or placental
      vasculature. Despite these changes, neither GR138950 nor captopril were
      detrimental to the outcome of pregnancy when foetal blood loss was kept to a
      minimum.

PMID- 8886427
TI  - Increased interleukin-8 release by beta-adrenoceptor activation in human
      transformed bronchial epithelial cells.
AB  - 1. The effect of beta-adrenoceptor activation on release of the neutrophil
      chemoattractant, interleukin-8 (IL-8), was examined in human transformed
      bronchial epithelial cells (16HBE cells). 2. The combined beta 1- and beta 2
      adrenoceptor agonist, isoprenaline, time- (100 nM, 2-18 h) and concentration- (1
      30 nM) dependently increased IL-8 protein content in the cell culture supernatant
      as measured by an enzyme immunosorbent assay standardized for DNA by fluoro
      colorimetry. 3. Isoprenaline (1-100 nM, 15 min) increased cyclic AMP
      concentration-dependently. 4. The effect of isoprenaline (100 nM) was inhibited
      by the beta-adrenoceptor blocker propranolol (10 microM). The maximum magnitude
      of IL-8 increase caused by beta-adrenoceptor activation was 40% of that caused by
      the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha 100 ng ml
      1). 5. The selective beta 2-adrenoceptor agonist salbutamol (1 microM), increased
      IL-8 protein similarly to isoprenaline and the cyclic AMP analogue, dibutyryl
      cyclic AMP (1 mM) produced a corresponding effect. 6. Pretreatment with
      isoprenaline (100 nM) followed by TNF-alpha (20 ng ml-1) increased IL-8
      additively. 7. In conclusion, beta-adrenoceptor stimulation increased the release
      of the neutrophil chemoattractant, IL-8 in 16HBE cells, via an increase in
      intracellular cyclic AMP. beta-adrenoceptor stimulation adds to the IL-8 increase
      caused by the pro-inflammatory cytokine TNF-alpha. If this mechanism exists in
      vivo, beta-adrenoceptor activation may increase neutrophil chemotaxis into the
      airways.

PMID- 8886428
TI  - Different subtypes of alpha 1A-adrenoceptor mediating contraction of rat
      epididymal vas deferens, rat hepatic portal vein and human prostate distinguished
      by the antagonist RS 17053.
AB  - 1. The alpha 1-adrenoceptor subtype mediating contraction of the rat hepatic
      portal vein to phenylephrine was characterized by use of competitive antagonists
      previously shown to have selectivity between the expressed alpha 1-subtype
      clones. Prazosin competitively antagonized the phenylephrine contractions with a
      pA2 value of 9.2, as did WB 4101 (pA2 9.4), 5-methyl urapidil (pA2 8.6),
      indoramin (pA2 8.4) and BMY 7378 (pA2 6.5). 2. The pA2 values on the rat portal
      vein correlated highly with their previously published pA2 values for the alpha
      1A-adrenoceptors mediating contraction of the rat epididymal vas deferens and
      human prostate and poorly with those for the alpha 1B- and alpha 1D-adrenoceptors
      mediating contraction of the rat spleen and aorta, respectively. The antagonist
      pA2 values on the rat portal vein correlated highly with their previously
      published pK1 values for the expressed alpha 1a-clone and poorly with those for
      the expressed alpha 1b- and alpha 1d-clones. Therefore the results show that
      contraction of the rat portal vein to phenylephrine is mediated by alpha 1A
      adrenoceptors. 3. The novel alpha 1-adrenoceptor antagonist RS 17053 had a
      relatively high affinity for the alpha 1A-adrenoceptors mediating contraction of
      the rat epididymal vas deferens (pA2 9.5) compared with the alpha 1B
      adrenoceptors in the rat spleen (pA2 7.2) or the alpha 1D-adrenoceptors in the
      rat aorta (pKB 7.1), in agreement with its selectivity for the expressed alpha 1a
      clone. However, RS 17053 had over 100 fold lower affinity for the alpha 1A
      adrenoceptors mediating contraction of the rat portal vein (pKB 7.1) and human
      prostate (pKB 7.1) compared with its affinity for the alpha 1A-adrenoceptors in
      the rat epididymal vas deferens or the expressed alpha 1a-clone. 4. The
      difference in affinity of RS 17053 between the rat epididymal vas deferens and
      rat portal vein cannot be explained by a species difference in the receptor.
      Therefore RS 17053 may distinguish between subtypes of the alpha 1A-adrenoceptor
      in the rat portal vein and human prostate compared with those in the rat
      epididymal vas deferens or the expressed alpha 1a-clone.

PMID- 8886430
TI  - Inhibition of nitric oxide synthase by 1-(2-trifluoromethylphenyl) imidazole
      (TRIM) in vitro: antinociceptive and cardiovascular effects.
AB  - 1. The ability of a range of substituted imidazole compounds to inhibit mouse
      cerebellar neuronal nitric oxide synthase (nNOS), bovine aortic endothelial NOS
      (eNOS) and inducible NOS (iNOS) from lungs of endotoxin-pretreated rats was
      investigated. In each case the substrate (L-arginine) concentration employed was
      120 nM. 2. 1-(2-Trifluoromethylphenyl) imidazole (TRIM) was a relatively potent
      inhibitor of nNOS and iNOS (IC50S of 28.2 microM and 27.0 microM respectively)
      but was a relatively weak inhibitor of eNOS (IC50, 1057.5 microM). The parent
      compound, imidazole, was a weak inhibitor of all three NOS isoforms (IC50S: nNOS,
      290.6 microM; eNOS, 101.3 microM; iNOS, 616.0 microM). Substitution of imidazole
      with a phenyl group to yield I-phenylimidazole (PI) resulted in an isoform non
      selective increase in inhibitory potency (IC50S: nNOS, 72.1 microM; eNOS, 86.9
      microM; iNOS, 53.9 microM). Further substitution of the attached phenyl group
      resulted in an increase in nNOS and a decrease in eNOS inhibitory potency as in
      TRIM, 1-chlorophenylimidazole (CPI; IC50S: nNOS, 43.4 microM; eNOS, 392.3 microM;
      iNOS, 786.5 microM) and 1-(2,3,5,6-tetrafluorophenyl) imidazole (TETRA-FPI;
      IC50S; nNOS, 56.3 microM; eNOS, 559.6 microM; iNOS, 202.4 microM). 3. The ability
      of TRIM to inhibit mouse cerebellar nNOS activity in vitro was influenced by the
      concentration of L-arginine (0.12-10.0 microM) in the incubation medium. When
      mouse cerebellar nNOS was used as enzyme source a double reciprocal (Lineweaver
      Burk) plot in the presence/absence of TRIM (50 microM) revealed a competitive
      inhibitory profile. The K(m) for L-arginine and the Ki for TRIM calculated from
      these data were 2.4 microM and 21.7 microM, respectively. The ability of TRIM to
      inhibit mouse cerebellar nNOS activity in vitro was unaffected by varying the
      time of exposure of the enzyme to TRIM from 0-60 min at 0 degree C. 4. TRIM
      exhibits potent antinociceptive activity in the mouse as evidenced by inhibition
      of acetic acid induced abdominal constrictions. The ED50 for TRIM following i.p.
      administration was 20 mg kg-1 (94.5 mumol kg-1). The antinociceptive effect of
      TRIM was reversed by pretreatment of animals with L-arginine (50 mg kg-1, i.p.)
      and was not accompanied by sedation, motor ataxia or behavioural changes
      (rearing, crossing, circling, dipping) as assessed by use of a box maze
      procedure. 5. L-NG nitro arginine methyl ester (L-NAME, 20 mg kg-1, i.v.) but not
      TRIM (0.5-20 mg kg-1, i.v.) increased mean arterial blood pressure (MAP) in the
      urethane-anaesthetized rat. 6. L-NAME (100 microM) potentiated the contractile
      response of the rabbit isolated aorta to phenylephrine (ED50; 0.084 +/- 0.01
      microM in the presence and 0.25 +/- 0.05 microM in the absence of L-NAME; maximum
      response, 7.7 +/- 0.4 g in the presence and 5.6 +/- 0.5 g in the absence of L
      NAME, n = 6, (P < 0.05) whilst TRIM (1-100 microM) was without effect. L-NAME
      (100 microM) but not TRIM (1-100 microM) also reduced carbachol-induced
      relaxation of the phenylephrine-precontracted rabbit aorta preparation. 7. L-NAME
      (50 microM) potentiated the vasoconstrictor effect of bolus-injected
      noradrenaline (10-1000 nmol) and reduced the vasodilator effect of carbachol (10
      microM) added to the Krebs reservoir in the rat perfused mesentery preparation. L
      NAME (50 microM) also reduced nitric oxide (NO) release (measured by
      chemiluminescence of nitrite in the Krebs perfusate) in response to noradrenaline
      (100 nmol; 53.8 +/- 4.0 pmol ml-1 in the presence and 84.8 +/- 8.0 pmol ml-1 in
      the absence of L-NAME, n = 15, P < 0.05) and carbachol (10 microM; 63.9 +/- 5.0
      pmol ml-1 in the presence and 154.0 +/- 9.0 pmol ml-1 in the absence of L-NAME, n
      = 15, P < 0.05). TRIM (50 microM) did not affect either the vasoconstrictor
      response to noradrenaline or the vasodilator response to carbachol or the
      accompanying release of NO from the perfused rat mesentery.

PMID- 8886429
TI  - Inhibition of nicotinic responses of bovine adrenal chromaffin cells by the
      protein kinase C inhibitor, Ro 31-8220.
AB  - 1. The effects of the protein kinase C inhibitor, Ro 31-8220, on the responses of
      cultured bovine adrenal chromaffin cells to nicotine, phorbol 12, 13-dibutyrate
      (PDBu) and K+ have been investigated. 2. Tyrosine hydroxylase activity was
      measured in situ in intact cells by measuring 14CO2 evolved following the
      hydroxylation and rapid decarboxylation of [14C]-tyrosine offered to the cells.
      Secretion of endogenous adrenaline and noradrenaline was measured by use of
      h.p.l.c. with electrochemical detection. Cyclic AMP levels were measured in cell
      extracts by RIA. 3. Ro 31-8220 produced a concentration-dependent inhibition of
      300 nM PDBu-stimulated tyrosine hydroxylase activity with an IC50 of < 2 microM
      and complete inhibition at 10 microM. It had no effect on the responses to
      forskolin. 4. Ro 31-8220 produced a concentration-dependent inhibition of 5
      microM nicotine-stimulated tyrosine hydroxylase activity, adrenaline and
      noradrenaline secretion and cellular cyclic AMP levels, with an IC50 of about 3
      microM and complete inhibition by 10 microM. At concentrations up to 10 microM,
      Ro 31-8220 had little or no effect on the corresponding responses to 50 mm K+. 5.
      A structural analogue of Ro 31-8220, bisindolylmaleimide V, that lacks activity
      as a protein kinase C inhibitor, had no effect up to 10 microM on PDBu-stimulated
      tyrosine hydroxylase activity or on nicotine-stimulated cyclic AMP levels or
      noradrenaline secretion and only marginal inhibitory effects on nicotine
      stimulated tyrosine hydroxylase activity and adrenaline secretion. 6. A
      structurally related protein kinase C inhibitor, bisindolylmaleimide I, inhibited
      PDBu-stimulated tyrosine hydroxylase activity with an IC50 of < 1 microM and
      complete inhibition by 3 microM, but had essentially no effect on nicotine
      stimulated tyrosine hydroxylase activity or catecholamine secretion. 7. The
      results suggest that Ro 31-8220 is not only a protein kinase C inhibitor but is
      also a potent inhibitor of nicotinic receptor responses in adrenal chromaffin
      cells by a mechanism unrelated to protein kinase C inhibition. The results are
      consistent with Ro 31-8220 being a nicotinic receptor antagonist.

PMID- 8886431
TI  - Antioxidant protection of NO-induced relaxations of the mouse anococcygeus
      against inhibition by superoxide anions, hydroquinone and carboxy-PTIO.
AB  - 1. The potential protective effect of several antioxidants [Cu/Zn superoxide
      dismutase (Cu/Zn SOD), ascorbate, reduced glutathione (GSH), and alpha-tocopherol
      (alpha-TOC)] on relaxations of the mouse anococcygeus muscle to nitric oxide (NO;
      15 microM) and, where appropriate, nitrergic field stimulation (10 Hz; 10 s
      trains) was investigated. 2. The superoxide anion generating drug duroquinone
      (100 microM) reduced relaxations to exogenous NO by 54 +/- 6%; this inhibition
      was partially reversed by Cu/Zn SOD (250 u ml-1), and by ascorbate (500 microM).
      Following inhibition of endogenous Cu/Zn SOD activity with diethyldithiocarbamate
      (DETCA), duroquinone (50 microM) also reduced relaxations to nitrergic field
      stimulation (by 53 +/- 6%) and this effect was again reversed by Cu/Zn SOD and by
      ascorbate. Neither GSH (500 microM) nor alpha-TOC (400 microM) afforded any
      protection against duroquinone. 3. Xanthine (20 mu ml-1); xanthine oxidase (100
      microM) inhibited NO-induced relaxations by 73 +/- 14%, but had no effect on
      those to nitrergic field stimulation, even after DETCA treatment. The inhibition
      of exogenous NO was reduced by Cu/Zn SOD (250 u ml-1) and ascorbate (400 microM),
      but was unaffected by GSH or alpha-TOC (both 400 microM). 4. Hydroquinone (100
      microM) also inhibited relaxations to NO (by 52 +/- 10%), but not nitrergic
      stimulation. In this case, however, the inhibition was reversed by GSH (5-100
      microM) and ascorbate (100-400 microM), although Cu/Zn SOD and alpha-TOC were
      ineffective. 5. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
      (carboxy-PTIO, 50 microM) inhibited NO-induced relaxations by 50 +/- 4%, but had
      no effect on nitrergic responses; the inhibition was reduced by ascorbate (2-200
      microM) and alpha-TOC (10-200 microM), but not by Cu/Zn SOD or GSH. 6.
      Hydroxocobalamin (5-100 microM) inhibited, equally, relaxations to both NO (
      logIC40 3.14 +/- 0.33) and nitrergic stimulation (-logIC40 3.17 +/- 0.22). 7.
      Thus, a number of physiological antioxidants protected NO from superoxide anions,
      and from direct NO-scavengers. The possibility that the presence of these
      antioxidants within nitrergically-innervated tissues might explain the lack of
      effect of the NO inhibitors on nerve-induced relaxation, without the need to
      invoke a transmitter other than free radical NO, is discussed.

PMID- 8886432
TI  - Pharmacological and functional characterization of bradykinin receptors in canine
      cultured tracheal epithelial cells.
AB  - 1. A direct [3H]-bradykinin ([3H]-BK) binding assay has been used to characterize
      the BK receptors in canine cultured tracheal epithelial cells (TECs). Based on
      receptor binding assay, TECs have specific, saturable, high-affinity binding
      sites for [3H]-BK. 2. The specific [3H]-BK binding was time- and temperature
      dependent. Equilibrium of association of [3H]-BK with the BK receptors was
      attained within 30 min at room temperature and 1 h at 4 degrees C, respectively.
      3. Analysis of binding isotherms yielded an apparent equilibrium dissociation
      constant (KD) of 1.5 +/- 0.2 nM and a maximum receptor density (Bmax) of 53.2 +/-
      5.2 fmol mg-1 protein. The Hill coefficient for [3H]-BK binding was 1.00 +/-
      0.02. The association (K1) and dissociation (K-1) rate constants were (7.6 +/-
      1.1) x 10(6) M-1 min-1 and (9.2 +/- 1.5) x 10 M-3 min-1, respectively. KD,
      calculated from the ratio of K-1 and K1, was 1.2 +/- 0.3 nM, a value close to
      that calculated from Scatchard plots of binding isotherms. 4. Neither a B1
      receptor selective agonist (des-Arg9-BK, 0.1 nM - 10 microM) nor antagonist
      ([Leu8, des-Arg9]-BK, 0.1 nM - 10 microM) significantly inhibited [3H]-BK binding
      to TECs, which excludes the presence of B1 receptors in canine TECs. 5. The
      specific binding of [3H]-BK to canine TECs was inhibited by the B2 receptor
      selective antagonists ([D-Arg0, Hyp3, Thi5, D-Tic7, Oic8]-BK (Hoe 140, 0.1 nM-10
      microM) and [D-Arg0, Hyp3, Thi5.8, D-Phe7]-BK, 0.1 nM - 10 microM) and agonists
      (BK and kallidin, 0.1 nM-10 microM) with a best fit by a one-binding site model.
      The order of potency for the inhibition of [3H]-BK binding was kallidin = BK =
      Hoe 140 > [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK. 6. BK and kallidin significantly
      induced concentration-dependent accumulation of IPs with a half-maximal response
      (EC50) at 17.6 +/- 3.5 and 26.6 +/- 5.3 nM, respectively, while the B1-selective
      agonist, des-Arg9-BK did not stimulate IPs accumulation and the B1-selective
      antagonist [Leu8, des-Arg9]-BK did not inhibit BK-induced IPs accumulation. Two
      B2-selective antagonists, Hoe 140 and [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK,
      inhibited BK-stimulated IPs accumulation with apparent pKB values of 8.8 +/- 0.3
      and 7.0 +/- 0.3, respectively. 7. It is concluded that the pharmacological
      characteristics of the BK receptors in canine cultured TECs are primarily of the
      B2 receptor subtype which might regulate the function of tracheal epithelium
      through the activation of this receptor subtype coupling to PI hydrolysis.

PMID- 8886433
TI  - Regulation of human basophil function by phosphatase inhibitors.
AB  - 1. Okadaic acid, a cell permeant inhibitor of protein serine/threonine
      phosphatases (PPs), attenuated the IgE-mediated release of the pre-formed
      mediator, histamine from human basophils in a time- and dose-dependent manner.
      Optimal inhibition (77 +/- 4%, P < 0.0001) of histamine release was observed
      following a 2 h incubation with 1 microM okadaic acid. 2. Okadaic acid and two
      analogues of okadaic acid were also studied and were found to inhibit the IgE
      dependent release of histamine. Concentrations required to inhibit release by 50%
      (IC50) were 0.6 microM for okadaic acid and 7.5 microM for okadaol, whereas
      okadaone was inactive. 3. The structurally-unrelated PP inhibitor, calyculin A,
      also inhibited IgE-dependent histamine release from basophils dose-dependently
      and was approximately six fold more potent than okadaic acid. 4. The IgE-mediated
      generation of sulphopeptidoleukotrienes (sLT) from basophils was inhibited by
      okadaic acid and related analogues with the following rank order of potency;
      okadaic acid (approx. IC50 0.3 microM) > okadaol (3 microM) > okadaone
      (inactive). 5. Okadaic acid, okadaol and okadaone (all at 3 microM) inhibited the
      IgE-mediated generation of the cytokine interleukin 4 (IL4) from human basophils
      by 67 +/- 9% (P < 0.002), 48 +/- 14% (P < 0.05) and 8 +/- 7% (P = 0.31),
      respectively. 6. Extracts of purified human basophils liberated 32P from
      radiolabelled glycogen phosphorylase and this PP activity was inhibited by 17 +/-
      3% (P < 0.0005) by a low (2 nM) concentration of okadaic acid and was inhibited
      by 96 +/- 1% (P < 0.0001) by a higher (5 microM) concentration of okadaic acid.
      Because a low (2 nM) concentration of okadaic acid inhibits PP2A selectively
      whereas a higher (5 microM) concentration inhibits both PP1 and PP2A, these
      findings suggest that both PP1 and PP2A are present in basophils. 7. In total
      these data suggest that PPs are resident in human basophils and that PPs may be
      important in the regulation of basophil function.

PMID- 8886434
TI  - The public health basis of cancer screening: principles and ethical aspects.

PMID- 8886435
TI  - The theoretical basis for cancer screening.

PMID- 8886436
TI  - Principles of economic evaluation in cancer screening.

PMID- 8886437
TI  - Screening for cervical cancer.

PMID- 8886438
TI  - Advances in screening for colorectal cancer.

PMID- 8886439
TI  - Advances in screening for breast cancer.

PMID- 8886440
TI  - Prostate cancer screening: current issues.

PMID- 8886441
TI  - Screening for gastric cancer.

PMID- 8886442
TI  - Screening for lung cancer.

PMID- 8886443
TI  - Screening for melanoma.

PMID- 8886444
TI  - Screening for neuroblastoma.

PMID- 8886445
TI  - Screening for cancer in high-risk families.

PMID- 8886446
TI  - Screening in developing countries: problems and opportunities.

PMID- 8886447
TI  - P-glycoprotein-mediated multidrug resistance: experimental and clinical
      strategies for its reversal.
AB  - The study of the cellular, biochemical, and molecular biology and pharmacology of
      MDR has provided one of the most active and exciting areas within cancer research
      and one that holds great promise for translation into clinical benefit. While
      convincing evidence for the functional role of P-gp in mediating clinical drug
      resistance in humans remains elusive, studies of the clinical expression of P-gp
      and trials of chemosensitizers with cancer chemotherapy suggest "resistance
      modification" strategies may be effective in some tumors with intrinsic or
      acquired drug resistance. However, even if P-gp-associated MDR proves to be a
      relevant and reversible cause of clinical drug resistance, numerous problems
      remain to be solved before effective clinical chemosensitization may be achieved.
      Such factors as absorption, distribution, and metabolism; the effect of
      chemosensitizers on chemotherapeutic drug clearance; toxicity to normal tissues
      expressing P-gp; and the most efficacious modulator regimens all remain to be
      defined in vivo. Clearly, the identification of more specific, potent, and less
      clinically toxic chemosensitizers for clinical use remains critical to the
      possible success of this approach. Nonetheless, the finding that a number of
      pharmacological agents can antagonize a well-characterized form of experimental
      drug resistance provides promise for potential clinical applications. Further
      study of chemosensitizers in humans and the rational design of novel
      chemosensitizers with improved activity should define the importance of MDR in
      clinically resistant cancer.

PMID- 8886448
TI  - Multidrug resistance associated with overexpression of MRP.

PMID- 8886449
TI  - Mechanisms of resistance to alkylating agents.

PMID- 8886450
TI  - Glutathione S-transferases.

PMID- 8886451
TI  - Role of DNA repair in resistance to drugs that alkylate O6 of guanine.
AB  - The mechanism of cytotoxicity of a number of chemotherapeutic agents involves
      alkylation at the O6 position of guanine, a site that strongly influences
      cytotoxicity. Repair of these lesions by the alkyltransferase protects from
      cytotoxicity and is a major mechanism of resistance to these agents. O6
      benzylguanine inhibition of alkyltransferase sensitizes tumor cells, and clinical
      trials are underway to determine its efficacy. The use of gene therapy to enhance
      the expression of alkyltransferase in hematopoietic cells may prevent dose
      limiting myelosuppression and may enhance the utility of this class of
      chemotherapeutic agents.

PMID- 8886452
TI  - Paclitaxel (Taxol): mechanisms of Resistance.

PMID- 8886453
TI  - Mechanisms of clinical resistance to 5-fluorouracil chemotherapy.

PMID- 8886454
TI  - Antifolates: current developments.
AB  - In summary, the problem of MTX resistance has been approached in a mechanistic
      fashion, based on the wealth of information generated over the years. To date,
      these strategies have produced several new classes of anticancer drugs, with a
      variety of anticipated and unanticipated mechanisms of action. Several of these
      have shown promising preclinical activity, and these are moving into more
      stringent testing in the clinic.

PMID- 8886455
TI  - Human immunodeficiency virus replication in the presence of antiretroviral drugs:
      analogies to antineoplastic drug resistance.
AB  - There are many analogies between antineoplastic therapy and antiviral therapy.
      For each there may be sanctuary sites in which the drug is ineffective because of
      decreased accumulation of the active form of the drug or increased competition by
      naturally occurring inhibitors. These sanctuaries may be restricted to anatomic
      or biochemical subsets of the population. A knowledge of these sanctuaries is
      essential to an understanding of the failure of therapy and for the design of
      more effective treatments. Eradication of these sanctuary sites may be important
      because they may be responsible for the viral replication or tumor cell division
      that continues to generate the diversity that drives clonal evolution.
      Ultimately, diversity as a consequence of the accumulation of mutations results
      in the selection of resistant viral or tumor cell variants and the failure of
      drug therapy. Maximizing therapy in an attempt to diminish the rate of generation
      of this diversity may result in better clinical outcomes, including a delay in
      the generation of variants with genetic drug resistance.

PMID- 8886456
TI  - Cellular resistance to topoisomerase poisons.

PMID- 8886457
TI  - Acquisition of an antiestrogen-resistant phenotype in breast cancer: role of
      cellular and molecular mechanisms.

PMID- 8886458
TI  - Androgen receptor mutations in prostate cancer.

PMID- 8886459
TI  - Retinoids in clinical cancer therapy.

PMID- 8886460
TI  - Apoptosis and cancer chemotherapy.

PMID- 8886461
TI  - Interaction of chemotherapy and biological response modifiers in the treatment of
      melanoma.

PMID- 8886462
TI  - Multifunctional modulators of drug resistance.

PMID- 8886463
TI  - How far have we come in dealing with the emotional challenge of abuse and
      neglect?

PMID- 8886464
TI  - The abused child as parent.
AB  - Free-response memories and current descriptions of self, parents, babies, and
      significant others generated by 55 mothers who were physically abused as children
      were compared with memories and descriptions by 46 mothers who were not
      physically abused. The two groups of mothers were matched for age of baby, race,
      and socioeconomic status. It was found that clusters of negative attributes
      pervaded the memories and perceptions that abused mothers had of others,
      particularly parents. Moreover, the degree of negative elaboration (i.e., the
      number of negative clusters attributed to others) discriminated the abused and
      control groups almost perfectly. It was also found for both groups that the more
      elaborated the positive view of self and others, the more secure the attachment
      of infant to mother. In addition, patterns of identification and description were
      dramatically different between the two groups: Unlike the comparison mothers,
      abused mothers tended to disidentify with their own mothers and to be
      inconsistent in their characterization of them.

PMID- 8886465
TI  - The effect of war on children.
AB  - The objective of this paper is to provide an overview of the effects of war on
      children during the 20th century. It is argued that wars have both direct and
      indirect effects on the population. It also is noted that wars have changed from
      being "conventional" to being of "low intensity". Under these latter
      circumstances civilians, including children, as well as the infrastructure of the
      society become targets whereas in the past, the targets were usually only
      military ones. The effects of the strategy used in "low intensity" conflicts is
      the disruption of the medical, social, educational, and public services of a
      country and the terrorization of the population. Under these circumstances
      children suffer inordinately. Their homes are destroyed, their families
      disrupted, and their chances of becoming mature productive members of society are
      compromised.

PMID- 8886466
TI  - Evaluation of the effectiveness of Project Trust: an elementary school-based
      victimization prevention strategy.
AB  - This study employed a Posttest-Only Control Group Design to assess the effects of
      a victimization prevention program, Project TRUST, on elementary school students'
      knowledge of general prevention concepts, knowledge of difficult-to-acquire
      prevention concepts, anxiety, and reporting of abuse. A selected subgroup of
      experimental subjects was also assessed for retention of acquired concepts over
      time. Students exposed to Project TRUST demonstrated significantly greater
      knowledge of maltreatment prevention information, as well as difficult-to-acquire
      concepts, than control group students. A 3-month delayed reassessment of the
      experimental subgroup showed no loss in acquired prevention information. No
      differences in anxiety scores existed between experimental and control groups.
      First-time student abuse disclosures were greater in the experimental than in the
      control group. These findings support the effectiveness of Project TRUST as a
      strategy to increase prevention knowledge and generate abuse disclosures without
      creating student anxiety.

PMID- 8886467
TI  - Assessing risk in families affected by substance abuse.
AB  - A new instrument assessing risk in substance abuse-affected families is
      presented. The instrument assesses those dimensions of substance abuse that make
      it more difficult for parents to meet the basic needs of their children. It also
      assesses those components of the parent's environment that may increase risk to
      the family's well-being. Information is presented on the instrument's reliability
      and validity. The article concludes with a discussion of the issues involved in
      assessing the risk for child abuse and neglect in families where there is an
      identified substance abuse problem.

PMID- 8886468
TI  - The prevalence and context of incest abuse in Finland.
AB  - The prevalence and context of father-daughter incest was surveyed in Finland in
      connection with a larger study about physical and sexual child abuse in 1988. A
      random sample of 409 comprehensive school classes with about 9,000 15-year-olds
      were asked to fill out questionnaires anonymously. The majority (93%) responded
      in the privacy of the school nurse's office, the rest in their classrooms. Eighty
      nine percent of the selected classes participated in the survey and the response
      rate of the students in those classes was 96%. Girls reporting sexual experiences
      with their father or stepfather was 5%. Girls reporting experiences with their
      biological father was 2% and 3.7% of the girls living with a stepfather reported
      sexual experiences with him. This survey shows that the feelings of the girls
      about their incestual experiences are overwhelmingly negative. The results are
      compared with prevalence estimates from the U.S. and the Nordic countries.

PMID- 8886469
TI  - The influence of case and professional variables on identification and reporting
      of physical abuse: a study with medical students.
AB  - Identification and reporting of suspected cases of maltreatment are important
      precursors to intervention, as maltreating parents typically do not self-refer
      for treatment. Professionals from various disciplines are legally mandated to
      report suspected cases of child maltreatment, yet incidences of abuse can remain
      unidentified or unreported. Identification of physical abuse often depends on
      careful consideration of the characteristics of the injuries and the plausibility
      of the explanations provided for the injuries. Many variables impact
      identification, as well as the subsequent decision of whether or not to report
      the case if abuse is suspected. The study examined the influence of three case
      variables (injury severity, plausibility of explanation, and time to seek medical
      attention) and two professional variables (gender of subject and amount of
      clinical experience) on how medical students respond to hypothetical cases of
      abuse. As part of the study, the responses of medical students were compared to
      those of practicing physicians. Subjects evaluated 16 different vignettes, each
      describing an injured child, rated whether injuries may have resulted from
      physical abuse, and indicated what further action should be taken with the case,
      including whether it should be reported. Results indicated a significant three
      way interaction between injury severity, injury explanation, and delay. Subject
      gender and amount of clinical experience did not influence identification.
      Significant positive correlations between identification and reporting were
      found. Correspondence between the responses of medical students and physicians
      was quite strong. Implications for clinical training of mandated reporters and
      directions for future research are discussed.

PMID- 8886470
TI  - The prevalence of a history of childhood sexual abuse in an acute adult inpatient
      population.
AB  - The prevalence of a history of childhood sexual abuse in a series of admissions
      to a general psychiatric hospital was estimated. One hundred and twenty subjects
      were surveyed using a self-administered questionnaire. Case notes were examined
      to determine previous documented disclosure, diagnosis, and rates of admission
      and deliberate self harm. Forty-six percent reported a history of childhood
      sexual abuse by questionnaire. Case note review revealed a rate of 14% of
      previously documented disclosure. The patterns of abuse broadly correspond with
      those usually reported as causing problems with adjustment in adult life. It may
      be concluded that a high proportion of psychiatric inpatients report a history of
      childhood sexual abuse many of whom have not disclosed this history to their
      psychiatrists.

PMID- 8886471
TI  - Adolescent abuse in Hong Kong Chinese families.

PMID- 8886472
TI  - Gradual disclosure by sexual assault victims--a sacred cow?

PMID- 8886473
TI  - How do children tell? The disclosure process in child sexual abuse.
AB  - Children's disclosure of sexual abuse has been described as a quasi-developmental
      process that includes stages of denial, reluctance, disclosure, recantation, and
      reaffirmation (Sorenson & Snow, 1991, Summit, 1983). It has been reported that
      nearly 75% of sexual abuse victims initially deny abuse, and that nearly 25%
      eventually recant their allegations (Sorenson & Snow, 1991). The present study
      examined disclosures in 234 sexual abuse cases validated by Protective Services
      in El Paso, Texas. Denial of abuse occurred in 6% of cases, and recantation in 4%
      of cases in which a child had already disclosed abuse. Four of the eight victims
      who recanted appeared to do so in response to pressure from a caretaker. The
      Child Sexual Abuse Accommodation Syndrome described by Summit (1983) seems to be
      infrequent among the types of cases seen by child protection agencies. The
      present findings do not support the view that disclosure is a quasi-developmental
      process that follows sequential stages.

PMID- 8886474
TI  - Attenuated blood pressure responsiveness during post-exercise hypotension.
AB  - OBJECTIVE: To test the hypotheses that acute treadmill exercise would produce
      post-exercise hypotension (PEH) and that PEH would be associated with reduced
      mean arterial pressure (MAP) responsiveness to the alpha 1-adrenergic agonist
      phenylephrine. METHODS: Arterial and venous catheters were implanted into
      exercise-trained female Dahl-salt sensitive rats (n = 9) for measurement of
      pulsatile blood pressure (BP) and heart rate (HR). The changes in BP following
      ganglionic blockade (hexamethonium/atropine) and the MAP responses to
      phenylephrine (PE) injections after ganglionic blockade (GB) were examined on
      separate days in testing cages (control) and following 40 min of treadmill
      exercise (post-ex). RESULTS: Thirty minutes following graded treadmill exercise
      (20-40 m/min, 0% grade, 40 min duration) blood pressure was significantly reduced
      (-9 +/- 1) mmHg compared to control. After exercise, GB produced a 43 +/- 3 mmHg
      decrease in BP which tended (p = 0.08) to be less than the reduction observed
      during control studies (51 +/- 2 mmHg). PE-induced increases in BP were
      significantly lower post-ex than control for each of the dosages tested (0.5, 1.0
      and 2.0 micrograms/kg). CONCLUSIONS: These results demonstrate that there is
      sustained reduction in PE-induced MAP responsiveness which accompanies exercise
      induced decreases in blood pressure in the Dahl salt-sensitive rat. Thus,
      decreased alpha-adrenoceptor responsiveness may contribute to the production of
      PEH.

PMID- 8886475
TI  - Cardiovascular characteristics in normotensive subjects with or without family
      history of hypertension.
AB  - The aim of our study was to evaluate whether initial changes of cardiovascular
      structure and/or function can be detected in young normotensive subjects with
      (F+) and without (F-) family history of hypertension. Thirty-two subjects (19 F+,
      10 males and 9 females, age range 17-32 years; 13 F-, 6 males and 7 females, age
      range 19-33 years) were studied. In each subject 24 hours ambulatory blood
      pressure monitoring, a M-mode, 2d guided and pulsed doppler echocardiogram and
      postischemic forearm strain gauge plethysmography were performed. The two groups
      of subjects did not differ for causal systolic and diastolic BP and 24 hours
      systolic and diastolic ambulatory monitored blood pressure. No differences in LV
      end-diastolic and end-systolic diameters, as well as in LV wall thickness, and in
      LV mass index were observed. Systolic functional parameters were also similar in
      the two groups. In F+ subjects peak early filling velocity was reduced in respect
      to F- (p < 0.01), peak late filling velocity integral was increased (p < 0.05)
      and the ratio of peak E/peak A integrals was decreased (p < 0.05). No difference
      was observed for postischemic forearm blood flow and minimal vascular resistance,
      taken as an index of arteriolar structural changes as well as intima-media
      thickness of carotid arteries. In conclusion in this study F+ and F- had similar
      BP values, LV mass and min VR; differences previously observed in LV mass between
      F+ and F- may have been due to the presence of different basal levels of BP; in
      F+ LV diastolic filling, although still in the normal range, shifted early toward
      the pattern of LV filling usually observed in hypertensive patients.

PMID- 8886476
TI  - Plasma endothelin-1 levels in patients with aldosterone-producing adenoma and
      pheochromocytoma.
AB  - The aim of the study was to evaluate possible changes of plasma endothelin-1
      levels (ET-1) in patients with hypertension secondary to primary aldosteronism
      and pheochromocytoma. We enrolled in the study: 12 patients affected by
      aldosterone-producing adenoma (5 M and 7 W; mean age 42.1 +/- 17.2 years); 8
      patients with pheochromocytoma (5 M, 3 W; mean age 36.2 +/- 17.1 years); 15
      patients with essential hypertension (9 M, 6 W; mean age 48.5 +/- 10 years). We
      also enrolled a normal control group (8 M, 12 W; mean age 34.2 +/- 11 years). The
      mean plasma ET-1 concentrations in patients with pheochromocytoma were
      significantly higher (23.9 +/- 5.2 pg/ml) than those in normal subjects (7.3 +/-
      1.9 pg/ml), in patients with primary aldosteronism (12.1 +/- 3.8 pg/ml) and in
      patients with essential hypertension (9.2 +/- 3 pg/ml); p < 0.001, respectively.
      The present investigation demonstrates that in human adrenal hypertension
      patients with pheochromocytoma have increased circulating ET-1 levels respect to
      patients with aldosterone-producing adenoma.

PMID- 8886477
TI  - Role of the circulating renin-angiotensin system in the pathogenesis of
      hypertension in transgenic rats. TGR(mREN2)27.
AB  - Transgenic rats, termed TGR(mREN2)27, which carry the mouse ren2d renin gene,
      develop fulminant hypertension. To evaluate the role of the circulating renin
      angiotensin system (RAS) in hypertension of TGR(mREN2)27, we determined plasma
      levels of its components and their regulation by ether-stress. Plasma prorenin
      was elevated in prehypertensive and in adult heterozygous TGR(mREN2)27
      (fourtyfold), when compared with Sprague Dawley (SD) controls, whereas plasma
      renin concentration (PRC) and angiotensin II were not in SD rats ether anesthesia
      increased PRC at day (11 a.m.; fivefold), but not at night (11 p.m.). Ether had
      no effect on PRC in TGR(mREN2)27. In contrast, ether increased plasma
      corticosterone levels at day and night in both strains to a similar degree. Our
      data indicate that plasma active renin is not a pathogenetic factor for
      hypertension in TGR(mREN2)27 and suggest a primary role of circulating prorenin.
      The lack of stimulation of PRC by ether in TGR(mREN2)27 probably reflects
      predominant extrarenal origin of renin.

PMID- 8886478
TI  - Adrenomedullin: changes in circulating and cardiac tissue concentration in Dahl
      salt-sensitive rats on a high-salt diet.
AB  - Adrenomedullin (AM), a novel hypotensive peptide, is suggested to be involved in
      defense mechanisms against hypertension, however, the detail mechanisms have not
      been clarified. To elucidate whether AM synthesis would be altered in a salt
      dependent hypertension, we have investigated the AM concentration and AM
      messenger RNA (mRNA) level in tissues of Dahl salt-sensitive rats on either low-
      or high-salt intake. The AM concentration in cardiac ventricle of the high-salt
      group was significantly higher than that of the low-salt group. The plasma AM
      concentration was also significantly higher in the high-salt group than in the
      low-salt group. Furthermore, the plasma AM concentration correlated well with the
      weight of left ventricle. RNA blot analysis revealed that the AM mRNA level in
      cardiac ventricle of the high-salt group was higher than that of the low-salt
      group. These results suggest that AM participates in the pathophysiology of salt
      dependent hypertension and plays a role in cardiac hypertrophy.

PMID- 8886479
TI  - Altered arachidonic acid metabolism contributes to the failure of dopamine to
      inhibit Na+,K(+)-ATPase in kidney of spontaneously hypertensive rats.
AB  - Dopamine decreases tubular sodium reabsorption in part by inhibition of Na+,K(+)
      ATPase activity in renal proximal tubules. The signaling mechanism involved in
      dopamine-mediated inhibition of Na+,K(+)-ATPase is known to be defective in
      spontaneously hypertensive animals. The present study was designed to evaluate
      the role of phospholipase A2 (PLA2) and its metabolic pathway in dopamine-induced
      inhibition of Na+,K(+)-ATPase in renal proximal tubules from Wistar-Kyoto (WKY)
      rats and spontaneously hypertensive rats (SHR). Renal proximal tubular
      suspensions were prepared and Na+,K(+)-ATPase activity was measured as ouabain
      sensitive adenosine triphosphate hydrolysis. Dopamine inhibited Na+,K(+)-ATPase
      activity in a concentration (1 nM-10 microM)-dependent manner in WKY rats while
      it failed to inhibit the enzyme activity in SHR. Dopamine (10 microM)-induced
      inhibition of Na+,K(+)-ATPase activity in WKY rats was significantly blocked by
      mepacrine (10 microM), a PLA2 inhibitor, suggesting the involvement of PLA2 in
      dopamine-mediated inhibition of Na+,K(+)-ATPase. Arachidonic acid (a product
      released by PLA2 action) inhibited Na+,K(+)-ATPase in a concentration-dependent
      (1-100 microM) manner in WKY rats while the inhibition in SHR was significantly
      attenuated (IC50: 7.5 and 80 microM in WKY rats and SHR, respectively).
      Furthermore, lower concentrations of arachidonic acid stimulated (30% at 1
      microM) Na+,K(+)-ATPase activity in SHR. This suggests a defect in the metabolism
      of arachidonic acid in SHR. Proadifen (10 microM), an inhibitor of cytochrome P
      450 monoxygenase (an arachidonic acid metabolizing enzyme) significantly blocked
      the inhibition produced by arachidonic acid in WKY rats and abolished the
      difference in arachidonic acid inhibition of Na+,K(+)-ATPase between WKY rats and
      SHR. These data suggest that PLA2 is involved in dopamine-induced inhibition of
      Na+,K(+)-ATPase and altered arachidonic acid metabolism may contribute to reduced
      dopaminergic inhibition of Na+,K(+)-ATPase activity in spontaneously hypertensive
      rats.

PMID- 8886480
TI  - Mechanisms of myocardial protection by amino acids: facts and hypotheses.
AB  - 1. Positive inotropic effect of taurine and improvement of cardiac performance of
      failing heart are mediated through the modulation of Ca2+ movement through the
      sarcolemma. 2. Cardioprotection with glutamate and aspartate is related to
      enhanced anaerobic energy formation in mitochondria coupled with succinate
      formation and, probably, with the relieving of glycolytic flux. During
      reperfusion, both amino acids replenish the malate-aspartate shuttle reactants,
      thereby facilitating glucose oxidation. 3. Increased intracellular concentrations
      of branched chain amino acids (leucine, valine and isoleusine) stimulate
      formation of acetyl-coenzyme (CoA) and succinyl-CoA and, thus, recovery of
      oxidative metabolism. 4. Methionine and cysteine enhance force of contraction by
      N-methylation of membrane phospholipids of the sarcolemma and sarcoplasmic
      reticulum. Methionine and, to a lesser extent, cysteine may reduce myocardial
      damage by oxygen radical species. 5. Histidine exerts antioxidant properties as a
      scavenger of singlet oxygen and OH radicals. High concentrations of histidine
      provide intracellular buffering to stimulate anaerobic energy formation.

PMID- 8886481
TI  - Augmented endothelium-dependent constriction to hypoxia early and late following
      reperfusion of the canine coronary artery.
AB  - 1. Canine coronary arteries with intact endothelium respond to hypoxaemia or
      serotonin infusion with dilatation, but when the endothelium is injured or
      dysfunctional, these stimuli can cause constriction. The present studies
      investigated whether or not regional ischaemia and reperfusion alter endothelium
      dependent responsiveness of canine coronary arteries in vivo and in vitro. 2. In
      organ chamber experiments, isolated control and reperfused coronary artery rings
      were contracted with prostaglandin F2 alpha and exposed to hypoxia (PO2 less than
      5 mmHg). 3. Hypoxia augmented the response of reperfused arteries more than that
      of controls. The hypoxic augmentation was blocked by NG-monomethyl-L-arginine, an
      inhibitor of nitric oxide synthesis from L-arginine. 4. These findings
      demonstrate that early following coronary reperfusion the hypoxic augmentation,
      which is mediated by a nitric oxide-dependent pathway in the endothelium, is
      facilitated. 5. In vivo studies revealed hyperconstriction of reperfused arteries
      in response to hypoxaemia (PO2 = 30-40 mmHg) and administration of either
      serotonin or ergonovine. 6. Twelve weeks following reperfusion injury, coronary
      arteries still exhibited augmented endothelium-dependent hypoxic augmentations in
      vitro, which were inhibited by NG-monomethyl-L-arginine. 7. Furthermore, resting
      coronary segments with endothelium displayed hypoxia-induced contractions that
      could not be inhibited by indomethacin, the lipoxygenase inhibitor AA861,
      superoxide dismutase plus catalase, deferoxamine, ouabain, or NG-monomethyl-L
      arginine. 8. These endothelium-dependent hypoxic response may play a role in the
      pathogenesis of hyperconstriction (vasospasm) following coronary reperfusion.

PMID- 8886482
TI  - 11 beta-Hydroxysteroid dehydrogenase type I enzyme in the hearts of normotensive
      and spontaneously hypertensive rats.
AB  - 1. The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) converts
      glucocorticoids to their inactive 11-keto metabolites. The ubiquitous expression
      of the NADP-dependent isoform (11 beta HSD1) suggest an important role in
      modulating glucocorticoid action, but little is known about 11 beta HSD1 gene
      expression and enzymatic activity in the rat heart. 2. In the present study rat
      cardiac 11 beta HSD1 activity and ontogeny of gene expression have been
      characterized. The addition of NADP, but not NAD, to heart homogenates resulted
      in significant increases in the metabolism of both corticosterone and cortisol,
      with the former substrate displaying far greater metabolism. Both 11 beta HSD1
      gene expression and enzyme activity increased in parallel from low levels at 1
      week of age to maximal levels at 8 weeks, with no further change by 16 weeks of
      age. 3. We also compared the activity of 11 beta HSD1 in the hearts of male and
      female spontaneously hypertensive rats (SHR) with normotensive Wistar-Kyoto (WKY)
      controls. Enzyme activity in the pooled atria of female SHR was significantly
      higher than in male SHR atria (7.6 +/- 0.6% conversion of corticosterone vs 4.5
      +/- 0.5%; P < 0.05). The left ventricles of female WKY rats contained
      significantly less 11 beta HSD activity than either male WKY rats or female SHR
      (8.6 +/- 0.8% conversion vs 17 +/- 1.4 and 13.6 +/- 0.5%, respectively; P <
      0.05). In the right ventricle, female WKY rats also had significantly less enzyme
      activity than either female SHR or male WKY rats (4.9 +/- 0.7 vs 10.0 +/- 1.7 and
      10.2 +/- 1.4%; P < 0.05). 4. These results clearly show that the rat heart
      contains significant amounts of the 11 beta HSD1 enzyme and that this activity is
      sexually dimorphic. Furthermore, significant differences were observed between a
      normotensive and hypertensive strain of rat. The relevance of these observations
      to the aetiology and maintenance of hypertension remains to be explored.

PMID- 8886483
TI  - Effects of exercise on intraocular pressure in physically fit subjects.
AB  - 1. Several studies have shown that exercise reduces intraocular pressure (IOP) in
      sedentary subjects, but the effects of exercise in physically fit subjects are
      not fully known. Accordingly, the present study was planned to investigate the
      effects of exercise on intraocular pressure in physically fit subjects after
      elimination of those factors that can affect intraocular pressure and have been
      neglected by previous studies. 2. Thirty-two sedentary males of the same age
      group were categorized equally into control and experimental groups. Intraocular
      pressures were measured during and after exercise with the Goldmann applanation
      tonometer. The experimental group took a supervised exercise programme of 3
      months duration. Physical fitness was evaluated by the measurements of maximum
      oxygen uptake. Each subject was tested twice by the same exercise protocol at an
      interval of 3 months. 3. After 3 months, resting IOP values decreased by 0.31 +/-
      0.11 (P < 0.05) and 1.37 +/- 0.15 mmHg (P < 0.001) in control and experimental
      groups, respectively. The acute decreases following the first exercise test were
      4.18 +/- 0.41 and 4.38 +/- 0.47 mmHg, while after 3 months these values were 4.12
      +/- 0.45 and 2.69 +/- 0.28 mmHg in control and experimental groups, respectively.
      After exercise conditioning, the mean recovery time was reduced by 43.03%. 4. The
      results are relevant to planning trials in glaucoma. Physical fitness reduces IOP
      and causes significant attenuation in the IOP response to physical exercise. It
      would seem reasonable at present not to discourage patients who have glaucoma
      from light exercise; perhaps, on the contrary, it should be encouraged.

PMID- 8886484
TI  - Effects of tetrandrine and closely related bis-benzylisoquinoline derivatives on
      cytosolic Ca2+ in human leukaemic HL-60 cells: a structure-activity relationship
      study.
AB  - 1. Previously it has been shown that tetrandrine (TET), a bis-benzylisoquinoline
      alkaloid, isolated from a Chinese herb Stephania tetrandra, can block non-voltage
      operated Ca2+ entry activated by intracellular Ca2+ store depletion induced by
      thapsigargin (TSG) and can release intracellular Ca2+ in HL-60 cells. The present
      study attempted to identify the chemical group(s) of the TET molecule responsible
      for these dual effects. The effects of TET and its closely related analogues,
      hernandezine (HER) and berbamine (BER), on Ca2+ entry and Ca2+ release were
      compared in fura-2-loaded HL-60 cells. 2. Berbamine was much less potent (IC50 =
      200 mumol/L) than TET and HER (both IC50 values = 25 mumol/L) in inhibiting Ca2+
      entry activated by TSG. Furthermore, at 100 mumol/L, BER was much less effective
      than TET and HER in suppressing TSG-induced Mn2+ entry. At 30-100 mumol/L, BER
      was significantly less effective than both TET and HER in causing Ca2+ release
      from internal stores. However, only BER was able to cause store depletion
      activated Ca2+ entry (or the so-called 'capacitative Ca2+ entry') upon Ca2+
      readmission. 3. Taken together, the data from this structure-activity
      relationship study reveal that the -OCH3 group of one particular benzene ring of
      TET, which distinguishes TET from BER, in part produces the dual pharmacological
      actions of TET.

PMID- 8886485
TI  - Magnolol reduces infarct size and suppresses ventricular arrhythmia in rats
      subjected to coronary ligation.
AB  - 1. Magnolol is an active component of Magnolia officinalis. It is 1000-times more
      potent than alpha-tocopherol in inhibiting lipid peroxidation in rat heart
      mitochondria. In the present study, the in vivo antiarrhythmic and anti-ischaemic
      effects of magnolol in coronary ligated rats were investigated. 2. Male Sprague
      Dawley rats were anaesthetized with urethane. Magnolol, at dosages of 10(-7), 10(
      8) and 10(-9) g/kg, was administered intravenously 15 min before ligation of the
      coronary artery. 3. The incidence and duration of ventricular tachycardia and
      ventricular fibrillation during 30 min coronary ligation were significantly
      reduced by magnolol. Ventricular arrhythmias during 10 min reperfusion after the
      relief of coronary ligation were also reduced. 4. In rats subjected to 4 h
      coronary ligation, 10(-7) and 10(-8) g/kg magnolol significantly reduced infarct
      size. 5. We conclude that magnolol may protect the myocardium against ischaemic
      injury and suppress ventricular arrhythmia during ischaemia and reperfusion.

PMID- 8886486
TI  - Vesico-hepato-renal cycling of acidic drugs via their reactive acyl glucuronide
      metabolites? Studies with diflunisal in rats.
AB  - 1. Deconjugation-reconjugation cycling of acidic drugs is known to occur in vivo
      via the hydrolysis of their reactive acyl glucuronide metabolites during their
      circulation in the blood (systemic cycling) or during their passage through the
      gut after biliary excretion (enterohepatic cycling). Whether such cycling occurs
      after renal excretion via hydrolysis in the urinary bladder followed by
      absorption of liberated drug (vesico-hepato-renal cycling) was investigated in
      rats using diflunisal (DF) and its acyl glucuronide (DFAG) as model compounds. 2.
      After administration of DF (1 mg/0.5 mL buffer, pH 7) into the bladder of
      anaesthetized bile-exteriorized rats, DF appeared rapidly in plasma, achieving
      peak concentrations of 7 micrograms/mL at 1 h. At 4 h, 30% of the dose was
      recovered as metabolites, mainly DFAG and DF phenolic glucuronide (DFPG) in bile,
      while 30% was recovered as unchanged DF from the bladder. 3. By contrast, after
      intravesical administration of an equimolar amount of DFAG at pH 7 or 5, DFAG
      itself was not detectable in plasma. Plasma concentrations of DF were barely
      detectable, with only approximately 1% of the administered dose recovered as
      metabolites in bile. 4. The data thus show that, although DF itself undergoes
      facile absorption from the urinary bladder of healthy rats, vesico-hepato-renal
      cycling of DF via DFAG appears to be of only minor quantitative importance.

PMID- 8886487
TI  - Long-term effects of high calorie sucrose-enriched diet and streptozotocin
      induced diabetes on insulin resistance in spontaneously hypertensive rats.
AB  - 1. The effects of two experimental manipulations on insulin resistance were
      compared in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto
      (WKY) rats. Rats were fed a high calorie sucrose-enriched diet (high calorie
      diet) or were made diabetic by the injection of streptozotocin (STZ). 2. After
      treatment with the high calorie diet for 8 weeks, blood pressure increased in
      SHR, but not in WKY rats. In contrast, STZ treatment decreased blood pressure in
      SHR, but increased it in WKY rats. 3. Plasma glucose levels during oral glucose
      loading were higher in SHR than in WKY rats. Glucose tolerance was impaired to a
      greater extent by both the high calorie diet and STZ in SHR than in WKY rats.
      Hyperinsulinaemia induced by the high calorie diet was severe in SHR compared
      with WKY rats. 4. Abnormalities in lipid metabolism induced by a high calorie
      diet or STZ-induced diabetes were more marked in SHR than in WKY rats. 5. Steady
      state plasma glucose levels in the insulin suppression test were higher in SHR
      than in WKY rats, both of which were treated by either the high calorie diet or
      STZ. These findings indicate that insulin-stimulated glucose uptake by high
      calorie diet or STZ-induced diabetes was impaired to a greater extent in SHR than
      in WKY rats. 6. It is concluded, therefore, that SHR fed on high calorie diet or
      SHR with STZ-induced diabetes are suitable models to study the effects of
      antihypertensive treatment on glucose tolerance, insulin resistance or lipid
      metabolism as well as blood pressure.

PMID- 8886488
TI  - Hypotensive activity of aqueous extract of Andrographis paniculata in rats.
AB  - 1. The hypotensive activity of an aqueous extract of Andrographis paniculata was
      studied using chronic intraperitoneal (i.p.) infusions by osmotic pumps. The
      extract exhibited a dose-dependent hypotensive effect on the systolic blood
      pressure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum
      hypotensive dose determined was repeated in a study in SHR and their normotensive
      controls, Wistar-Kyoto (WKY) rats, to demonstrate its comparative effects on the
      SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as
      on lipid peroxidation in the kidneys, as measured by the thiobarbituric acid
      (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY
      rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were
      significantly lower in extract-treated SHR when compared with vehicle-treated SHR
      controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not
      significantly different between extract- and vehicle-treated WKY rats. 6. This
      study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR
      possibly by reducing circulating ACE in the plasma as well as by reducing free
      radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be
      different in WKY rats.

PMID- 8886489
TI  - Effects of Fuller's Earth and activated charcoal on oral absorption of paraquat
      in rabbits.
AB  - 1. Thirty male rabbits of local strain (weighing 1.5-2 kg) were divided into five
      groups. Four groups were treated with an oral dose of paraquat, which was
      followed by either Fuller's Earth or activated charcoal 0.5 or 2.0 h later. The
      remaining group acted as the control group and was treated only with an oral dose
      of paraquat. The dose of paraquat was 20.0 mg/kg given in a concentration of 20.0
      mg/mL. 2. Both adsorbents were administered in 15 mL normal saline as a 30%
      slurry. Blood was sampled from the ear vein 0.5, 1, 2, 4, 8 and 24h after the
      administration of paraquat. 3. Paraquat concentration was determined
      spectophotometrically at 600 nm by comparing against a standard curve of paraquat
      obtained by the addition of standard paraquat into normal rabbit serum and
      extracting interfering substances with ether. 4. The results of the present study
      show that either adsorbent can bring down the serum paraquat level. There was no
      significant difference found in the effectiveness of either adsorbent. 5. It is
      concluded that the administration of an adsorbent as early as possible will help
      in the reduction of paraquat absorption from the gastrointestinal tract. 6.
      Activated charcoal is still effective in lowering serum paraquat concentration
      when given more than 1 h after ingestion of paraquat.

PMID- 8886490
TI  - Changes in renal renin gene expression in fetal sheep.
AB  - 1. Renin gene expression was investigated in kidneys from 13 foetal and four
      adult sheep. 2. The levels of renal renin mRNA in foetuses were greater than
      those in adult sheep (P < 0.001). 3. There was no significant difference in renin
      mRNA levels between foetuses aged 91 and 134 days (term 150 days). 4. The levels
      of renin gene expression were higher (178 +/- 5 units; P < 0.001) in foetuses at
      142 days than levels in 91 (144 +/- 4 units) and 134 days old foetuses (146 +/- 6
      units). 5. It is concluded that the high level of renin gene expression in the
      foetal kidney is responsible for the high levels of renin in the foetal
      circulation.

PMID- 8886491
TI  - Neural control of the circulation in heart failure and coronary ischaemia:
      introduction.
AB  - 1. A large gap in our knowledge of the reflex control of the circulation still
      exists in the setting of chronic heart failure. This symposium will provide state
      of-the-art experimental data on the reflex regulation of the circulation in heart
      failure and myocardial ischaemia. 2. Alterations in arterial baroreflex and
      cardiopulmonary reflexes contribute to the increase in sympathetic tone in this
      disease state. Additionally, changes in neurohormones, such as angiotensin, are
      thought to contribute. 3. Coronary ischaemia is associated with activation of
      both vagal and sympathetic reflexes of cardiac origin. The balance between
      activation of these two reflexes will determine the ultimate change in
      sympathetic outflow. 4. Sensory endings in the myocardium are exquisitely
      sensitive to local mediators, such as prostaglandins, oxygen-derived free
      radicals, adenosine and bradykinin.

PMID- 8886492
TI  - Beta-adrenoceptor desensitization during the development of canine pacing-induced
      heart failure.
AB  - 1. The goal of this review is to emphasize four major points regarding the
      development of catecholamine desensitization in heart failure (HF). 2.
      Catecholamine desensitization occurs prior to the development of HF (i.e. after 1
      day of rapid pacing, physiological responses to beta-adrenoceptor stimulation are
      depressed by over 50%, yet no evidence of HF is observed for 3-4 weeks of rapid
      pacing). 3. Multiple mechanisms in the beta-adrenoceptor cascade are involved. In
      HF there are decreases in beta 1-adrenoceptors, high affinity beta-adrenoceptors,
      adenylyl cyclase activity and messenger RNA and increases in Gi. 4. Not all
      mechanisms appear simultaneously (i.e. early decreases occur in high affinity
      beta-adrenoceptors and adenylyl cyclase; late increases in Gi and decreases in
      beta-adrenoceptor density evolves). 5. Mechanisms distal to cAMP generation also
      play a role (i.e. alterations in ryanodine receptor binding and excitation
      contraction coupling also occur).

PMID- 8886493
TI  - Neural responses to exercise in humans: implications for congestive heart
      failure.
AB  - 1. During static handgrip exercise, muscle metaboreceptors are stimulated,
      evoking the 'exercise pressor reflex.' As part of this reflex, sympathetic
      discharge to skeletal muscle is increased. The muscle 'metaboreceptors' are
      thought to be free nerve endings of unmyelinated group IV nerve fibres. These
      receptors are stimulated by a number of metabolites, including lactic acid, H+,
      diprotonated phosphate, adenosine and the biproducts of prostaglandin synthesis.
      2. During chronic, repetitive activity, muscle metabolite-sensitive afferents may
      be desensitized. We speculate that metaboreceptor desensitization also occurs in
      congestive heart failure (HF). Despite this desensitization, sympathoexcitatory
      responses to forearm exercise are preserved. This suggest that some other neural
      system aside from muscle metaboreceptors must be activated to a greater degree in
      HF. We speculate that in HF the activity of muscle mechanoreceptors is increased.
      Furthermore, we believe that limb congestion can increase the discharge of muscle
      mechanoreceptors, thereby evoking non-metaboreceptor-mediated increases in
      sympathetic discharge. Future studies in our laboratory will examine the role
      limb congestion and decongestion play in evoking muscle mechano-receptor-mediated
      sympathoexcitatory responses.

PMID- 8886494
TI  - Cardiac vagal afferent stimulation by free radicals during ischaemia and
      reperfusion.
AB  - 1. Myocardial ischaemia and reperfusion can evoke excitation of cardiac vagal
      afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold
      Jarisch effect). We postulate that oxygen free radicals, which are well known to
      be produced during ischaemia and reperfusion, contribute to this excitation. 2.
      Activity from vagal afferent fibres in rats, whose endings were located in the
      walls of all four chambers of the heart, was recorded in response to topical
      application of pro-oxidant chemicals to the surface of the heart. Activity was
      also recorded from vagal afferent fibres, whose endings were located in the left
      ventricle, in response to occlusion of the left anterior coronary artery (LAC)
      for 30 min and subsequent reperfusion. A majority of the recorded fibres were
      classified as chemosensitive C-fibre endings due to their irregular discharge
      under resting conditions, their activation in response to the topical application
      of capsaicin (1-10 micrograms) to the surface of the heart encompassing the
      receptive field and their conduction velocities. 3. Topical application of either
      H2O2 or xanthine/xanthine oxidase to the heart activated 50% of the
      chemosensitive endings and did not directly affect cardiac mechanoreceptors. This
      effect was reproducible, dose-dependent and was not due to [H+]. 4.
      Administration of the superoxide radical scavenging enzyme, superoxide dismutase
      (20000 U/kg, i.v.), decreased the response of fibres to xanthine/xanthine oxidase
      but had no effect on the activation caused by H2O2. The antioxidants deferoxamine
      (20 mg/kg, i.v.) or dimethylthiourea (10 mg/kg, i.v.), which scavenge the
      hydroxyl radical, abolished the responses to xanthine/xanthine oxidase and H2O2.
      Administration of indomethacin (5 mg/kg, i.v.) had no effect on the afferent
      response to H2O2. 5. In response to ligation of the left anterior coronary (LAC),
      the activity of chemosensitive endings within the ischaemic zone increased within
      the first 2 min of occlusion. Endings outside the ischaemic zone were not
      affected at the beginning of ischaemia. Reperfusion activated only chemosensitive
      endings responsive to topical H2O2. These reperfusion-sensitive endings were
      located both within and outside the ischaemic zone of the left ventricle. 6.
      Indomethacin (5 mg/kg, i.v.) prevented activation of chemosensitive endings at
      the beginning of LAC occlusion regardless of their sensitivity to H2O2 but had no
      effect on the response to reperfusion. Conversely, deferoxamine (20 mg/kg, i.v.)
      had no effect on the activation of chemosensitive fibres at the onset of
      ischaemia, whereas it completely prevented activation at reperfusion. 7. We
      propose that there are two different mechanisms that activate chemosensitive
      afferent vagal fibres in the rat heart during ischaemia and reperfusion. The
      first causes excitation of these endings at the onset of ischaemia and is
      mediated by prostaglandin synthesis within the ischaemic zone. The second
      mechanism leads to a more widespread activation of chemosensitive afferents in
      the left ventricle during prolonged ischaemia and at the moment of reperfusion
      and is mediated by oxygen free radical formation.

PMID- 8886495
TI  - Reflexes mediated by cardiac sympathetic afferents during myocardial ischaemia:
      role of adenosine.
AB  - 1. Myocardial ischaemia and infarction activate vagal and sympathetic sensory
      endings in the ischaemic myocardium, resulting in powerful reflex effects. The
      vagal afferents are either mechano- or chemosensitive, whereas sympathetic
      afferents may be mechano-, chemosensitive or both. 2. Activation of vagal
      afferents results in sympathoinhibitory, cardioinhibitory, vasodepressor
      responses. Cardiac sympathetic afferents activated during myocardial ischaemia
      mediate sympathoexcitatory, vasoconstrictor cardioaccelerator responses. 3. The
      focus of the present review is on the activation of sympathetic afferents by
      myocardial ischaemia and on the resulting reflex responses that they mediate. 4.
      These endings are more likely to be activated as the degree of ischaemia
      progresses from subendocardial towards transmural. They are evenly distributed
      between the anterior and inferoposterior wall. Although it has been suggested
      that these endings are activated by bradykinin, recent evidence indicates that
      they are activated by adenosine released from the ischaemic myocardium. Results
      from our laboratory indicate that this effect is due to the activation of
      adenosine A1, but not adenosine A2 receptors. 5. Activation of ventricular vagal
      and sympathetic afferent fibres during myocardial ischaemia in humans is
      responsible for the autonomic changes observed and, in the case of the
      sympathetic afferents, for the sensation of angina pectoris.

PMID- 8886496
TI  - Loss of nitric oxide production in the coronary circulation after the development
      of dilated cardiomyopathy: a specific defect in the neural regulation of coronary
      blood flow.
AB  - 1. The aims of our study were to determine the role of nitric oxide (NO) in
      cholinergic reflex dilation of the coronary circulation in normal healthy
      conscious dogs and after the development of pacing-induced dilated cardiac
      myopathy and overt congestive heart failure. 2. Dogs were instrumented using
      sterile surgical techniques under general anaesthesia and allowed to fully
      recover. The Bezold-Jarisch reflex was stimulated by the intra-atrial injection
      of veratrine or the intravenous injection of PGI2, while the carotid chemoreflex
      was stimulated by the intracarotid injection of nicotine. Experiments were
      performed before and after the development of overt congestive heart failure (HF)
      caused by rapid left ventricular pacing for 4 weeks. 3. The release of NO, or NO
      mediated vascular relaxation following administration of acetylcholine (ACh) may
      have little physiological significance since as ACh is released from nerve
      endings in vivo. Stimulation of the Bezold-Jarisch or carotid chemoreflex
      resulted in typical vagal cholinergic reflex coronary vasodilation, an increase
      in coronary blood flow and a decrease in coronary vascular resistance, which was
      substantially reduced following NO synthesis inhibition with nitro-L-arginine. 4.
      After the development of severe congestive HF, the production of NO by sieved
      coronary microvessels from the heart was markedly reduced accompanied by a 60-80%
      reduction in both the mRNA (northern blot) and protein (western blot) for
      endothelial NO synthase in the aorta. 5. After the development of severe pacing
      induced HF, activation of the Bezold-Jarisch or carotid chemoreflex no longer
      resulted in coronary vasodilation due to the disappearance of NO production from
      the coronary circulation. 6. Therefore, cholinergic reflex coronary vasodilation
      is mediated by NO. Because coronary blood vessels lose the ability to produce NO
      after the development of HF, reflex cholinergic coronary vasodilation is markedly
      altered, uncovering a previously undiscovered specific defect in the integrated
      control of the coronary circulation in the failing heart.

PMID- 8886497
TI  - Neurohumoral activation in heart failure: role of paraventricular nucleus.
AB  - 1. A number of neurohumoral processes are activated in heart failure (HF),
      including an increase in the plasma concentration of noradrenaline. 2. Few
      studies have been performed to examine the role of the central nervous system
      (CNS) in the activation of sympathetic outflow during HF. In the present paper we
      review the limited studies performed to examine the role of the CNS in the
      activation of sympathetic outflow, with particular emphasis on our recent study
      that examined the activity of discrete regions of the brain as assessed by
      histological localization and photodensitometric quantification of the metabolic
      enzyme hexokinase during HF. 3. There were significant increases in hexokinase
      activity in the parvocellular (pPVN) and magnocellular (mPVN) divisions of the
      paraventricular nucleus of the hypothalamus and in the locus coeruleus (LC) in
      rats with HF. No changes in hexokinase activity were observed in the median
      preoptic area, supraoptic nucleus (SON) or posterior hypothalamus. 4. We conclude
      that HF is associated with changes in specific areas in the brain and that
      alterations in the activation of neurons in the pPVN, mPVN and LC are likely to
      be related to alterations in vasopressin production, blood volume regulation and
      sympathoexcitation observed in the HF state.

PMID- 8886498
TI  - Cardiovascular protection by ginsenosides and their nitric oxide releasing
      action.
AB  - 1. In an animal model in vivo, ginsenosides (GS), saponins from Panax ginseng,
      were shown to protect against myocardial ischaemia/reperfusion damage with
      concomitant increased 6-keto-PGF1 alpha and decreased lipid peroxidation. 2. In
      perfused rabbit lung in situ and isolated rabbit aortic rings, GS protected the
      pulmonary and aortic endothelium against electrolysis-induced free radical
      injury. Purified components of GS, Rb1 and especially Rg1, relaxed pulmonary
      vessels and this effect was eliminated by nitro-L-arginine, an inhibitor of
      nitric oxide (NO) synthase. 3. In cultured bovine aortic endothelial cells, GS
      enhanced the conversion of [14C]-L-arginine to [14C]-L-citrulline, indicating an
      increased release of NO. 4. As the neurotransmitter inducing penile erection, NO
      release was shown to be enhanced by GS in rabbit corpus cavernosum (CC) in vitro.
      Ginsenosides enhanced both acetylcholine-induced and transmural nerve stimulation
      activated relaxation associated with increased tissue cGMP. The latter effect was
      eliminated by tetrodotoxin and was associated with decreased tissue cGMP.
      Ginsenoside-enhanced CC relaxation was attenuated by nitro-L-arginine and
      oxyhaemoglobin, and enhanced by superoxide dismutase. 5. It is postulated that
      cardiovascular protection by GS may be partly mediated by the release of NO, a
      potent antioxidant, and that the GS-enhanced release of NO from endothelial
      cells, especially from perivascular nitric oxidergic nerves in the CC, may partly
      account for the aphrodisiac effect of Panax ginseng used in traditional Chinese
      medicine.

PMID- 8886499
TI  - Probing excitation-contraction coupling in trachealis smooth muscle with the
      mycotoxin cyclopiazonic acid.
AB  - 1. Muscarinic stimulation-induced tonic contraction of airway smooth muscle is
      independent of membrane potential. This contraction is not sensitive to
      inhibition by voltage-operated Ca2+ channel blockers or by K+ channel openers. 2.
      Cyclopiazonic acid (CPA) inhibits Ca2+ loading of internal stores but does not
      affect maximal tonic contraction induced by acetylcholine (ACh) in steady state
      conditions. 3. After depletion of internal Ca2+ stores with CPA, ACh-induced
      tonic contraction becomes dependent upon values of membrane potential. The
      contraction is then sensitive to voltage-operated Ca2+ channel blockers and to K+
      channel openers. 4. Treatment of trachealis muscle with CPA potentiates the M2
      mediated component of ACh stimulation, but this potentiation is not entirely
      responsible for the switch in excitation-contraction (E-C) coupling. 5. It is
      proposed that depletion of internal Ca2+ stores with CPA and promotion of M2
      stimulation can lead to a switch in E-C coupling in trachealis smooth muscle from
      pharmaco- to electromechanical mode, perhaps by targeting a plasma membrane K+
      channel.

PMID- 8886500
TI  - Antihypertensive effects of DL-tetrahydropalmatine: an active principle isolated
      from Corydalis.
AB  - 1. The effects of DL-tetrahydropalmatine (DL-THP) on cardio-vascular function and
      hypothalamic release of monoamines were assessed in rats under urethane
      anaesthesia. 2. Intravenous administration of DL-THP (1-10 mg/kg) produced
      hypotension, bradycardia, a decrease in hypothalamic serotonin and noradrenaline
      release and an increase in hypothalamic dopamine release in rats. 3.
      Intrahypothalamic administration of DOI (a serotonergic 5-HT2 receptor
      antagonist) or apomorphine (a dopamine D2-receptor agonist) produced the opposite
      effects and reversed DL-THP-induced hypotension and bradycardia. 4. The data
      suggest that DL-THP acts through the 5-HT2 and/or D2-receptor antagonism in the
      hypothalamus to induce hypotension and bradycardia in rats.

PMID- 8886501
TI  - A family of novel actin-inhibiting marine toxins.
AB  - 1. We have examined the effects of marine toxins with a macrolide structure on
      actin. These toxins include mycalolide B, aplyronine A and bistheonellide A. 2.
      Measuring actin polymerization by monitoring fluorescent intensity of pyrenyl
      actin, mycalolide B did not accelerate the actin polymerization but quickly
      depolymerized F-actin. In contrast, cytochalasin D, which inhibits actin
      polymerization by binding to the barbed end of F-actin, accelerated actin
      nucleation and depolymerized F-actin at a slower rate. 3. Analysing the kinetics
      of depolymerization by monitoring the rate of spontaneous depolymerization of F
      actin under the unpolymerizable state or the rate of polymerization where F-actin
      was seeded as a nucleus, mycalolide B was suggested to sever F-actin. 4. The
      relationship between the concentration of total actin and F-actin at different
      concentrations of mycalolide B suggests that mycalolide B forms a 1:1 complex
      with G-actin. Viscometry and electron microscopic observations further suggest
      that the actin filament was depolymerized by mycalolide B. Furthermore,
      mycalolide B suppressed actin-activated myosin Mg(2+)-ATPase activity, although
      cytochalasin D did not. Aplyronine A has similar effects on actin. 5.
      Bistheonellide A also depolymerized F-actin and sequestered G-actin by forming a
      1:2 complex with G-actins, but, its severing effect was not detected. We conclude
      that mycalolide B, aplyronine A and bistheonellide A are novel types of actin
      depolymerizing agents, the mechanism of action of which is different from that of
      cytochalasin D. These structurally related marine toxins may be categorized as
      'actin depolymerizing macrolides' and may serve as novel pharmacological tools
      for analysing actin-mediated cell functions.

PMID- 8886502
TI  - In vitro inhibitory effects of chebulinic acid on the contractile responses of
      cardiovascular muscles.
AB  - 1. The effects of chebulinic acid, which has been shown to elicit blood pressure
      lowering effect in rats, on aortic vascular contraction as well as cardiac
      contraction were studied in rats. 2. Chebulinic acid had no effect on KCl-induced
      aortic contraction, but irreversibly inhibited the contractile responses to
      phenylephrine in an apparently non-competitive manner. Chebulinic acid also
      inhibited contractile responses of rat aorta to 5-hydroxytryptamine and
      angiotensin II. 3. Chebulinic acid inhibited the binding of [3H]-prazosin to dog
      aortic microsomal membranes in a concentration-dependent manner with an IC50
      value of 0.34 mmol/L. Results of saturation binding experiments suggest a mixed
      mode of inhibition by chebulinic acid (i.e. a decrease in both the maximal number
      of binding sites and the affinity for prazosin). 4. Chebulinic acid concentration
      dependently and reversibly inhibited the maximal left ventricular pressure of rat
      heart in a Langendorff preparation with 50% inhibition occurring at a
      concentration of 0.3 nmol/L. 5. We conclude that chebulinic acid exerts non
      specific inhibitory actions in vascular preparations. Its inhibitory effect on
      cardiac contraction was reversible and three orders of magnitude more potent than
      that on vascular contraction. We suggest that the hypotensive effect of
      chebulinic acid is probably mediated via the decrease in cardiac output resulting
      from reduced left ventricular contraction.

PMID- 8886503
TI  - Tetrandrine as a calcium antagonist.
AB  - 1. The Ca(2+)-antagonism of tetrandrine (TET) on the Ca2+ mobilization in various
      types of cells were reviewed. Inositol trisphosphate (IP3)-generating drugs were
      used as Ca(2+)-mobilizing agonists and the effects were compared with those
      produced by using the microsomal Ca(2+)-ATPase inhibitor thapsigargin (TG), which
      is a tool for analysing Ca2+ store-regulated Ca2+ entry (capacitative Ca2+
      entry). 2. In rat phaeochromocytoma PC12 cells, 100 mumol/L TET abolished high K+
      (30 mmol/L)-induced sustained increases in cytoplasmic Ca2+ concentrations
      ([Ca2+]i) and partially inhibited bradykinin (1 mumol/L)- or TG (100 nmol/L)
      induced Ca2+ entry. 3. In NIH/3T3 fibroblasts and rat parotid acinar cells, 100
      mumol/L TET abolished Ca2+ entry induced by bombesin (1 mumol/L) and carbachol
      (100 mumol/L), respectively, or TG (100 nmol/L). However, in the human leukaemia
      T cell line Jurkat, 100 mumol/L TET did not inhibit Ca2+ entry evoked by either
      the anti-CD3 antibody OKT3 (10 mg/L) or TG (100 nmol/L). 4. In rat glioma C6
      cells, the effects of TET on Ca2+ mobilization were further examined. At a high
      concentration, TET (300 mumol/L) alone did not affect [Ca2+]i in C6 cells.
      Tetrandrine inhibited the peak and sustained increases in [Ca2+]i induced by
      bombesin and TG in a dose-dependent manner. Although TET or TG did not produce
      increases in IP3, TET did inhibit increases in IP3 produced by bombesin. 5. Our
      results suggest that the action of TET on Ca2+ entry is dependent on cell types
      and that TET inhibits both Ca2+ entry from the extracellular medium and Ca2+
      release from intracellular stores in rat glioma C6 cells.

PMID- 8886504
TI  - Plasma follistatin concentrations increase following lipopolysaccharide
      administration in sheep.
AB  - 1. The effect of inflammation induced by lipopolysaccharide (LPS) injection on
      plasma follistatin (FS) concentrations was investigated. 2. Plasma FS and tumour
      necrosis factor-alpha concentrations increase following LPS administration in
      ewes. 3. The rise in FS is similar, but more sustained, to that previously
      observed after surgery. 4. These results indicate a possible functional link
      between FS, inflammation and the acute-phase response.

PMID- 8886505
TI  - Arterial wall remodelling and stiffness in hypertension: heterogeneous aspects.
AB  - 1. Hypertension is associated with hypertrophy and decreased operating
      distensibility of the large artery wall. Because similar pathological and
      functional changes are observed with ageing, hypertension is often looked upon as
      an accelerated form of aging. 2. Considering the decrease in arterial
      distensibility observed with both ageing and hypertension, whether the change is
      due to age, an increase in distending pressure or to hypertension-induced changes
      in large artery structural properties may be much debated. 3. The purpose of the
      present review is to study the effects of aging and hypertension on structural
      (lumen diameter and arterial wall thickness) and functional (distensibility)
      properties of large central and medium-sized arteries in humans. 4. From clinical
      studies in subjects with hypertension with or without advanced renal disease, it
      is suggested that age- and hypertension-induced structural arterial changes are
      quite heterogeneous, depending on the topography of the vessel and on the
      severity of the underlying disease.

PMID- 8886506
TI  - Peripheral vasculature in essential hypertension.
AB  - 1. Haemodynamic evidence shows that in essential hypertension minimum vascular
      resistance and vascular pressor response are increased and that the vascular
      reserve is decreased. 2. The haemodynamic changes are most easily explained in
      terms of a generalized narrowing of the vasculature and an increase in the ratio
      between the thickness of the tunica media and the lumen diameter (media: lumen
      ratio), with no change in the functional properties of the smooth muscle itself.
      3. Histological and in vitro studies of resistance vessels confirm these
      predictions. Moreover, the evidence indicates that these changes are associated
      mainly with remodelling (rearrangement of the same amount of material) of the
      vessels, rather than growth. 4. Although the alteration in small artery structure
      is usually appropriate to the actual blood pressure, the structure appears not
      only to be a secondary adaptation, but is also dependent on other factors,
      including neurohumoral factors. 5. The available evidence shows that
      normalization of the resistance vessel structure (by increasing lumen diameter
      and decreasing the media:lumen ratio) should be achieved not by inhibition of
      growth but by (reverse) remodelling. Recent evidence from clinical investigations
      shows that this can be achieved in essential hypertensive patients treated with
      the angiotensin-converting enzyme inhibitor perindopril. 6. The role of the
      resistance vasculature as a primary determinant of blood pressure remains
      unclear. It is suggested that the requirement for normalization of resistance
      vascular structure is due to a need to increase the vascular reserve.

PMID- 8886507
TI  - Towards optimization of wave reflection: therapeutic goal for tomorrow?
AB  - 1. The conventional approach to drug therapy of hypertension and heart failure
      considers only effects of such drugs on peripheral resistance, cardiac output and
      heart rate. 2. A more complete approach needs to consider the pulsatile nature of
      cardiac ejection and so the influence of arterial stiffness and wave reflection
      properties and the effects of drugs on these. 3. Wave reflection normally aids
      cardiac function when full body height is achieved and arterial distensibility is
      high. However, with ageing or in hypertension the arteries stiffen and wave
      reflection returns early, augmenting systolic pressure, increasing pulse pressure
      and reducing the capacity for coronary perfusion. 4. In mature or older adults,
      delay of or reduction in wave reflection is an important therapeutic strategy for
      management of hypertension, angina pectoris and cardiac failure. 5. Beneficial
      effects of such therapy cannot always be gauged from conventional recordings of
      blood pressure, but can be inferred from analysis of pulse waveform.

PMID- 8886508
TI  - Role of the endothelium in the genesis of cardiovascular disease.
AB  - 1. Endothelial cells release nitric oxide (NO) and the putative endothelium
      derived hyperpolarizing factor (EDHF) in response to an increase in shear stress
      and receptor stimulation. 2. Tests of endothelial function have principally used
      acetylcholine (ACh)-mediated relaxation of precontracted isolated blood vessels
      or increases in forearm blood flow measured by venous occlusion plethysmography.
      Basal NO release is tested by a rise in resistance during infusion of the NO
      synthase inhibitor L-NMMA. Potential traps for investigators looking to evoke
      endothelial dysfunction following reduced ACh responses are discussed. 3.
      Endothelial dysfunction appears to occur in large but not small arteries in human
      and animal hypertension. Patients with long-standing congestive heart failure
      have endothelial dysfunction in buttock skin resistance arteries and there is
      coronary artery endothelial dysfunction following coronary ischaemia. 4.
      Remodelled arteries from neointimal thickening as a result of coronary collateral
      development in dog heart and new angiogenic vessel growth following large artery
      occlusion in the rabbit hindlimb appear to have normal endothelial function in
      relation to NO release. 5. Development of specific NO synthase inhibitors,
      antagonists of EDHF and the constrictor peptide endothelin, will clarify the role
      of these endothelium-derived factors in the cause or maintenance of vascular
      dysfunction. Defining redundancy and hierarchy of importance of these vascular
      factors are areas for future resolution.

PMID- 8886509
TI  - Endothelium-dependent responses and inhibition of angiotensin-converting enzyme.
AB  - 1. Experimental and clinical studies have demonstrated the efficacy of inhibitors
      of angiotensin-converting enzyme (ACE) in a variety of cardiovascular diseases.
      Both structural and functional improvements have been reported. 2. Hypertension,
      atherosclerosis, congestive heart failure or ageing are accompanied by
      endothelial dysfunctions. The vasoactive endothelium-derived relaxing factors,
      nitric oxide, endothelium-derived hyperpolarizing factor and prostacyclin, could
      be involved, depending on the pathology. 3. Some of the beneficial effects of ACE
      inhibitors may be due to the augmented release of these endothelial factors
      resulting from the protection of locally produced bradykinin, particularly at the
      endothelial level.

PMID- 8886510
TI  - Angiotensin-converting enzyme inhibitors and atherosclerosis: relevance of animal
      models to human disease.
AB  - 1. Most studies examining the effect of angiotensin-converting enzyme (ACE)
      inhibitors on atherosclerosis in experimental animals have used doses well in
      excess of those given clinically. 2. Using a rabbit model of cholesterol-induced
      atherosclerosis characterized by subendothelial lipid accumulations ('juvenile
      fatty streaks') in the aorta and atheromatous lesions in the pre-injured carotid
      artery, we examined the effect of perindopril (at doses approaching clinical
      relevance) on the development, progression and regression of atherosclerosis. 3.
      Administration of perindopril during the 6 weeks of cholesterol feeding reduced
      lipid accumulation in developing atheromatous plaques of the carotid artery and
      in fatty streaks of the aorta. In animals with pre-existing fat-filled lesions,
      perindopril inhibited progression of the disease in both vessels and aided lesion
      regression following return to a normal diet for up to 10 months. The protective
      effect of perindopril was not related to a decrease in blood pressure nor to an
      influence on serum cholesterol levels. 4. The bradykinin B2 receptor antagonist
      Hoe140 did not alter the effectiveness of perindopril in inhibiting either the
      development of atherosclerosis or vessel wall ACE activity, indicating that the
      anti-atherogenic effect of perindopril is not mediated through the B2 receptor.
      5. The angiotensin II (AngII) receptor antagonist losartan had no effect on the
      development of atherosclerotic plaques in this rabbit model, indicating that
      inhibition of AngII production is not the mechanism by which perindopril exerts
      its antiatherogenic effects.

PMID- 8886511
TI  - Markers for cardiovascular and renal morbidity: expectations for an intervention
      programme in an Australian aboriginal community.
AB  - 1. Australian Aborigines have high rates of both cardiovascular mortality and
      renal failure and the usual male dominance in these conditions is respectively
      reduced and effaced. 2. In one Aboriginal community, we have demonstrated a
      strong association between albuminuria and cardiovascular risk factors and a
      relationship of both with insulin resistance, which is more pronounced in females
      than males. 3. We propose that albuminuria is a component of Syndrome X and that
      reduction in levels of albuminuria should prove to be a useful marker of
      effectiveness in treatment programmes targeting cardiovascular risk as well as
      renal disease.

PMID- 8886512
TI  - Drugs and brain death: the clinician's perspective.

PMID- 8886513
TI  - Drugs and brain death: drug assay perspectives.
AB  - The ability to make any meaningful interpretation of a drug assay result is very
      dependent upon a knowledge of the limitations of the method(s) used (sensitivity,
      specificity etc.), and the concentration that may be measured in plasma and its
      relationship to CNS effects. We need more information about 'critical'
      concentrations for each drug and sedation in the setting of the brain-injured
      patient before meaningful interpretation can be applied to such data. While the
      above discussion is critical of screen-type assays, the alternative specific
      assays are not easily provided for, as obviously the resourcing of laboratories
      to be able to deliver such specialized services for a range of therapeutic drugs,
      in addition to 'social' drugs or other toxins (e.g. glues, pesticides, solvents,
      environmental substances etc), becomes an increasingly complex issue in the
      current economic climate. Hence, the analytical laboratory can offer valuable
      support to the clinical team however, the interpretation of such results must be
      assessed in the light of many limitations of such assay methods and not seen as
      the 'gold standard' for assessment of brain function.

PMID- 8886514
TI  - Drugs and brain death: a matter of 'practical certainty'.

PMID- 8886515
TI  - Drugs and brain death: a legal perspective.

PMID- 8886516
TI  - Drugs and brain death: a unifying approach.

PMID- 8886517
TI  - Relationships between blood drug concentrations and cerebral effects.

PMID- 8886518
TI  - Neuroprotective agents in severe head injury.

PMID- 8886519
TI  - Memory disorders in Alzheimer's disease and the organization of human memory.
AB  - The Squire and Zola-Morgan parallel organization model of the memory and the
      Tulving hierarchical model were developed mainly through the study of amnesic
      patients. The predictions of these two models are different, the first being more
      open to double dissociations and less restrictive than the second. Alzheimer's
      Disease is characterized by a differential impairment of the memory systems and
      by an interindividual variability which may take the form of dissociations
      between preserved and disturbed abilities in some patients. The objective of this
      study was to use the memory dysfunctions of patients with AD to test the validity
      of the two models. Analysis of the group data provided an average profile of
      memory disturbance consistent both with much of the data given in AD literature
      and with the two models. Using a multiple single-case strategy, we demonstrated
      several simple dissociations which are for the greater part compatible with the
      two models. Two of the dissociations underline the limits of the Tulving model,
      which otherwise accounts for a lot of results. The study supports the relevance
      of AD for the understanding of the cognitive architecture of the human memory.

PMID- 8886520
TI  - Visual and language processing disorders are concurrent in dyslexia and continue
      into adulthood.
AB  - A recent study by Slaghuis. Lovegrove and Davidson (1994) found that visual and
      language processing differences were concurrent in a group of preadolescent
      dyslexic. In the present study, two experiments are reported that investigate the
      concurrence and continuity of visual and language processing differences in
      groups of young and adult dyslexics on a measure of visual processing and a
      measure of phonological coding. The visual processing task in the present
      experiments was a measure of Ternus apparent movement which was used as an index
      of the duration of visible persistence. Ternus apparent movement is multistable
      and provides two mutually exclusive and easily distinguishable percepts for the
      observer, referred to as 'element' and 'group' movement, that are highly
      dependent on the temporal interval between frame 1 and frame 2 of the display.
      The language processing task in the present experiments was a test of
      phonological coding measured using a non-word test of 100 orthographically legal
      non-words. The results of the first experiment showed that in comparison to
      normal readers the young dyslexic participants showed a significant reduction in
      Ternus 'group movement' and a significant reduction in the pronunciation of non
      words. In a second experiment, Ternus apparent movement and performance on the
      non-word test was measured in groups of adult dyslexic and normal readers in
      order to investigate whether the visual and language processing differences found
      in young dyslexics were also present in adult dyslexics. The results showed that
      adult dyslexics also have a significant reduction in Ternus 'group movement' and
      a significant reduction in the ability to pronounce non-words similar to that
      found in the young dyslexic group in Experiment 1. The significant reduction in
      Ternus 'group movement' in dyslexic participants was explained in terms of an
      increase in the duration of visible persistence and was shown to be consistent
      with evidence for a transient system disorder. The combined results show that
      visual and language processing difference are concurrent in dyslexia and continue
      into adulthood.

PMID- 8886521
TI  - Autonomic and recognition indices of memory in amnesic and healthy control
      subjects.
AB  - Autonomic and recognition indices were examined in six amnesic subjects of mixed
      aetiology and six control subjects matched with respect to age, education and
      intelligence. The key objectives of this study were: (a) assess amnesics level of
      recognition and autonomic discrimination for recently shown words compared with
      controls; (b) determine if amnesics' level of autonomic discrimination was
      preserved when compared with the control subjects, level of recognition; and (c)
      assess confidence in hits and false alarms. The results showed that: (1) despite
      showing impaired recognition, amnesics displayed significantly better autonomic
      discrimination; (2) the level of autonomic discrimination displayed by amnesics
      did not significantly differ from the control subjects' level of recognition; (3)
      the level of confidence expressed in false alarms and hits did not significantly
      differ between amnesics and controls, which is in sharp contrast to the
      significantly greater levels of confidence expressed by healthy subjects in hits
      versus false alarms. If future work shows that amnesics display preserved
      autonomic discrimination for novel information, then it may suggest that, at
      least, some amnesics can store information to an extent that is comparable to
      that of healthy controls.

PMID- 8886522
TI  - Semantic memory following pediatric head injury: relationship to age, severity of
      injury, and MRI.
AB  - The effects of closed head injury (CHI) severity (mild vs. severe) and age at
      injury were analyzed in a longitudinal study (3. 12 months postinjury) of
      semantic memory which used magnetic resonance imaging (MRI) to characterize focal
      brain lesions. Semantic memory was evaluated by word and category fluency,
      semantic verification, semantic clustering in word list recall, and vocabulary.
      Episodic memory was assessed by word list recall. Comparison of normal control (n
      = 104) data with the patients' data (n = 77) at 3 months postinjury disclosed
      semantic and episodic memory deficits in the severe CHI patients. Analysis of the
      longitudinal data revealed significant effects of age at injury for all of the
      semantic memory measures. The effects of injury severity were confined to the
      latency of verifying correct statements. Volume of left frontal and extrafrontal
      lesions was predictive of performance on several semantic memory measures, but
      less robust for right hemisphere lesions.

PMID- 8886523
TI  - Left-handedness in twins: genes or environment?
AB  - Twin family data can cast light on the longstanding problem about the influences
      of genes and environment on the etiology of left-handedness. Therefore, hand
      preference was assessed in 1700 adolescent twin pairs and their parents. Left
      handedness (LH) appeared not significantly enhanced among twins compared to the
      general population. In addition the following observations were made: (1)
      Significant more LH in first born twins than in second born twins. (2)
      Significant higher left-handedness association in MZmm pairs compared to DZmm
      pairs and not or may be marginally so in MZff versus DZff pairs. These results,
      combined with the observations that (a) left-handed fathers increase the
      probability of LH in sons but not in daughters; (b) LH in mothers increases LH
      prevalence in both sons and daughters to the same degree; and (c) very low birth
      weight, corrected for the effect of gestational age, increases LH prevalence in
      first born twins only, make an environmental explanation more likely. The
      possibility that exposure to prenatal male hormones - to which low birth weight
      and high birth stress children are more vulnerable - might be a crucial condition
      for the etiology of LH, is discussed.

PMID- 8886524
TI  - Eye movement patterns in reading as a function of visual field defects and
      contrast sensitivity loss.
AB  - Saccadic eye movements during reading were examined as a function of the side of
      visual field cut and the impairment of visual contrast sensitivity Five patients
      with various visual field defects were compared to five age-matched controls.
      Patients with right visual field defect showed an increase in the number of
      rightward saccades and a decrease in their amplitude, and patients with left
      visual field defects showed a pattern more similar to that of the control
      subjects. Two patients showed a selective deficit in the range of medium-high
      spatial frequency; they were the only patients to show a lengthening of mean
      fixation time during reading. These results indicate selective effects on reading
      depending on primary sensory defects. The clinical relevance of these findings is
      briefly discussed.

PMID- 8886525
TI  - Memory abilities in children with Williams syndrome.
AB  - Williams syndrome (WS) is a rare genetic condition characterised by intellectual
      disability, typical facial dysmorphology and several medical anomalies. A
      specific neuropsychological profile with a dissociation between language
      (relatively preserved) and visuo-spatial abilities (more seriously impaired) has
      been hypothesised in these children. Memory abilities of these patients have not
      been adequately investigated, although they may substantially contribute to
      better understanding their neuropsychological profile. The present study aimed at
      investigating verbal and spatial memory in patients with WS (N = 16). Their
      performance was compared with that of normally developing children on tasks of
      verbal and spatial span and immediate and delayed recall of verbal and visuo
      perceptual materials. Memory abilities of WS children appear to be characterised
      by defective visuo-spatial memory, both in the short-term and long-term domain,
      and a dissociation between normal short- but deficient long-term verbal learning.
      Results are interpreted by supporting the thesis that intellectual disability
      reflects the defective functioning of a complex system in which some cognitive
      competencies may be disrupted more than others (Detterman, 1987; Vicari,
      Albertini and Caltagirone, 1992).

PMID- 8886526
TI  - A dissociation in naming digits and colors following commissurotomy.
AB  - Pairs of red and green digits were flashed in the opposite visual fields of L.B.,
      a man with complete forebrain commissurotomy. He was highly accurate in naming
      both digits, the green ones alone, or the red ones alone, regardless of field. In
      contrast, he was relatively poor at naming the colors of the digits in the left
      visual field, and in comparing colors between fields. This dissociation suggests
      either (a) that information about shape was tagged by color and transferred from
      right to left hemisphere, but information about color itself was not transferred,
      or, more likely (b) that L.B.'s right hemisphere has acquired the ability to
      overtly name highly familiar stimuli, such as digits, but not colors.

PMID- 8886527
TI  - Form-specific priming and functional brain asymmetries in perceptual
      identification.
AB  - Word form representations in intact cerebral hemispheres were studied by a
      lateralized perceptual identification priming task. During the study phase, word
      forms were primed by displaying words visually in uppercase or lowercase letters.
      During the test phase, perceptual identification of non-studied baseline words
      and studied words (presented in same or different lettercase as studied) was
      tested by displaying targets in the left or right visual field. Experiment 1
      showed that the hemispheric pattern of priming effects was dependent on the
      lettercase at test. For uppercase test items, only the left visual field/right
      hemisphere was sentitive to study-test changes in lettercase, replicating an
      earlier result obtained in word-stem completion (Marsolek, Kosslyn and Squire,
      1992). However, lowercase test items did not reveal any asymmetries in the form
      dependent priming component indicating that in some conditions form-specific
      representations are computed in the left hemisphere also. No asymmetries were
      found in the abstract, form-independent component of priming. Experiment 2
      revealed that use of explicit memory in the perceptual identification task
      eliminated the form-specific priming effects and suggested that the results of
      Experiment 1 were uncontaminated by explicit memory.

PMID- 8886528
TI  - Correlated auditory asymmetries in lexical and nonlexical tasks.
AB  - Two experiments address the question of whether different auditory verbal tasks
      produce correlated asymmetries. The first shows that ear asymmetries from
      dichotic word and syllable tasks do in fact correlate, but not to asymmetry from
      a visual face processing task. The second replicates the correlation between word
      and syllable asymmetries and shows that this significant relationship does not
      extend to another dichotic task involving the recognition of emotional tones of
      voice. The results are viewed as consistent with a left-hemisphere based
      "auditory linguistic" process involved in recognizing both lexical and nonlexical
      materials.

PMID- 8886529
TI  - Subtraction bugs in an acalculic patient.
AB  - We report a patient, MT, who presented a specific, though not isolated, deficit
      in written calculation. Despite a preserved knowledge of simple arithmetic -
      single-digit addition and subtraction - he failed systematically in multi-digit
      subtraction. The nature of errors was consistent across problems and reflected
      the application of a disturbed underlying algorithm. Moreover, the pattern of
      error observed mimies a very common finding in developmental studies on
      arithmetical procedure acquisition (Fuson, 1990, 1992, Young and O'Shea, 1981;
      VanLehn, 1986, 1990). The data suggest that, within calculation skills, syntax
      may exist as a system of stable, but inappropriate, rules which are independent
      of any underlying conceptual knowledge.

PMID- 8886530
TI  - La Peyronie and the experimental search for the seat of the soul:
      neuropsychological methodology in the eighteenth century.
AB  - The birth of scientific neuropsychology is traditionally considered to have taken
      place during the 19th century when disturbances or losses of specific mental
      functions were systematically correlated with post-mortem findings of localized
      cerebral pathology. Attempts at localizing psychic functions were of course made
      earlier, but they were usually not based on scientific observations with one
      notable and so far neglected exception. At the beginning of the 18th century the
      French surgeon Francois Gigot de La Peyronie systematically tried to correlate
      deficits of mental functions with autopsy findings. The methodological principles
      he formulated were sound and do not essentially differ from those used in modern
      scientific neuropsychology. His method was based on the systematic exclusion of
      those areas of the brain whose lesions are not associated with disruption of the
      faculties of the soul combined with the careful examination of cases where such
      association consistently exists. His conclusions were, however, disappointing
      from the modern point of view and he obviously failed to found a new scientific
      discipline. The reasons for this failure obviously lay in the dualistic
      presuppositions which made him look for the unique locus of mind-body interaction
      instead of localizing specific functions.

PMID- 8886532
TI  - What is going on? Part IV.

PMID- 8886533
TI  - The pants paresthesia syndrome: a ten-year follow-up.

PMID- 8886531
TI  - Newer aspects in the diagnosis, treatment, and prevention of non-small cell lung
      cancer. Part II.

PMID- 8886534
TI  - The non-Langerhans' cell histiocytoses in childhood.
AB  - The cutaneous histiocytoses are best divided in the Langerhans' cell
      histiocytoses and non-Langerhans' cell histiocytoses. In the former group, the
      cells react with S100 and CD1a antibodies, while in the latter group they express
      a variety of macrophage markers. Xanthogranuloma is a frequent childhood tumor
      and the only common non-Langerhans' cell histiocytosis. Xanthogranulomas contain
      a mixture of several different types of histiocytes that also appear in more pure
      forms as both solitary tumors and disseminated processes. The varying histiocyte
      morphology provides a unifying concept for non-Langerhans' cell histiocytoses.

PMID- 8886535
TI  - Stingray hickey.
AB  - A large number of injuries from stingrays are reported each year in the United
      States. Usually these injuries are inflicted by the stingray's tail, after the
      resting stingray is stepped on. The tail has a stinger that can cause puncture
      wounds with envenomation. We report a case in which an injury from a stingray was
      due to its bite.

PMID- 8886536
TI  - Early onset pretibial myxedema in the absence of ophthalmopathy: a morphologic
      evolution.
AB  - Pretibial myxedema (PTM) is an uncommon, late manifestation of Graves' disease.
      It is nearly always preceded by significant ophthalmopathy and classically
      presents as nonpitting (brawny) edema of the lower extremities. We report a case
      of PTM that is unusual because of its morphologic evolution, that it occurred
      prior to the diagnosis of Graves' disease, and in the absence of ophthalmopathy.

PMID- 8886537
TI  - Alternative therapies commonly used within a population of patients with
      psoriasis.
AB  - Alternative therapies are known to be employed by dermatology patients. This
      study investigates the use of alternative medical treatments for psoriasis and
      the sociodemographic variables, conventional medical treatment, and psoriasis
      disease severity. Our study population consisted of 578 university dermatology
      clinic patients with psoriasis and data was analyzed from 317 (55 percent)
      questionnaire respondents. The majority of our sample were women (57 percent) and
      nonwhites represented 8 percent of our sample. Psoriasis severity was measured
      using the validated Self-Administered Psoriasis Area and Severity Index.
      Alternative medicine was used by 62 percent of respondents. Excluding sunlight
      and nonprescription tanning equipment, 51 percent used one or more of the
      remaining alternative therapeutic modalities. The psoriasis severity was worse in
      those who had tried herbal remedies, vitamin therapy, and dietary manipulation.
      With the exception of vitamin therapy, we observed no association between the
      intensity of conventional medical treatment and alternative treatment. The
      present or prior use of herbal remedies was correlated with the use of vitamin
      therapy and sunbathing, and dietary interventions were significantly correlated
      with vitamin therapy. Of the 113 (36 percent) who had used nonprescription
      tanning equipment for their psoriasis, 68 percent believed this modality was
      effective. We found that alternative medical therapies were widely utilized by
      subjects participating in this study. Clinicians need to continue to be aware of
      nonallopathic remedies employed by their patients to discover useful information
      about future therapies and to monitor for adverse effects.

PMID- 8886538
TI  - Cutaneous herpes simplex virus, type I, in association with Staphylococcus aureus
      in an infant.
AB  - A 9-month-old infant was diagnosed as having impetigo of the central face. Her
      clinical condition deteriorated despite treatment with intravenous antibiotics.
      Viral and bacterial cultures grew herpes simplex virus type I and Staphylococcus
      aureus, respectively. The patient's condition improved rapidly with antiviral
      treatment in combination with antibiotics. Recognition of the possibility of a
      combined viral and bacterial infection is important so that adequate treatment is
      not delayed.

PMID- 8886539
TI  - Connatal herpes zoster.
AB  - We describe a case of connatal herpes zoster present in a newborn girl whose
      mother had been exposed to varicella infection during the seventh month of
      pregnancy. A few minutes after delivery, the newborn was examined for an
      erythematous maculopapular rash with clear grouped vesicles involving the right
      L2-L4 dermatome. She was given varicella zoster immunoglobulin and oral and
      topical acyclovir, and all the skin lesions were completely healed eight days
      later. This report emphasizes one aspect of the relationship between maternal
      exposure to varicella zoster virus infection and the occurrence of connatal
      shingles, the benign course of the disease in this case, and the favorable
      response to acyclovir therapy in neonates.

PMID- 8886540
TI  - Effect of ketoconazole-medicated shampoos on squamometry and Malassezia ovalis
      load in pityriasis capitis.
AB  - Pityriasis capitis is improved by the use of antifungal shampoos. A double-blind
      randomized, placebo-controlled study was conducted to compare the efficacy of
      ketoconazole 0.5 percent and 1 percent formulation shampoos. Evaluations were
      made in seventy-eight volunteers before and after a two-week duration of daily
      shampooing. Grading the Malassezia ovalis load in dandruff and values of
      squamometry were used as noninvasive methods to evaluate efficacy.

PMID- 8886541
TI  - Biomechanical considerations for orthodontic treatment of adults.
AB  - Biomechanical modifications made to accommodate orthodontic treatment of adult
      dentitions are generally minor and adhere to the basic laws of physics as they
      apply to all orthodontic tooth movement. Some adult presentations necessitate
      changes in treatment strategy from what would otherwise be employed in adolescent
      patients to achieve similar goals. In other cases, objective themselves may need
      to be modified because of a lack of growth potential, constraints of treatment
      mandated by the patient, or the presence of multiple missing or compromised
      teeth. The possibilities and limitations of orthodontic and dentofacial
      orthopedic treatment for adults are usually easier to define before beginning
      therapy than with adolescent patients because the unknown contribution that
      growth will make has already been discounted. By planning treatment and
      mechanotherapy taking into account the individual circumstances that may affect
      the patient's biological response to treatment, realistic goals of orthodontics
      can be mutually recognized and agreed on by both the provider and the patient
      before therapy is initiated.

PMID- 8886542
TI  - Optimal orthodontic space closure in adult patients.
AB  - The basic mechanical principles of various approaches to space closure to achieve
      treatment goals were presented. Practical methods for closing space were outlined
      with particular attention to controlling deleterious side effects. Special
      requirements for space closure in adult patients were addressed with specific
      recommendations for this category of tooth movement.

PMID- 8886543
TI  - Orthodontic procedures improving periodontal prognosis.
AB  - The wide range of interrelations between orthodontics and periodontology shows
      that besides the preventive significance in the mixed dentition, another focal
      point is the comprehensive rehabilitation of periodontally affected patients.
      With increasing experience in the field of adult orthodontics, setting
      therapeutic limits becomes increasingly difficult. It is impossible in principle
      to define in exact metric terms the probing depth or attachment loss up to which
      orthodontic tooth movement is feasible. The fact is rather that the orthodontic
      periodontal treatment goal can be defined only after evaluation in each
      individual finding a number of different factors: esthetics, function, risks of
      orthodontic tooth movement, biomechanical considerations, and periodontal
      prognosis.

PMID- 8886544
TI  - Management of severe vertical dimension problems.
AB  - This article illustrates some of the principles and diagnostic techniques that
      can be used to manage patients with vertical dimension problems. It is paramount
      to the treatment of these patients to make a proper diagnosis of the problem
      areas before doing a treatment plan. This involves the use of cephalometric
      analysis in both the static and the dynamic modes and using orthodontics and
      surgery to intrude or extrude differently segments or groups of teeth according
      to the patient's needs. This tends to simplify the treatment and the following of
      restorative and periodontal procedures.

PMID- 8886545
TI  - Combined orthodontic and prosthetic therapy. Special considerations.
AB  - The adult patient may present with a complex medical and dental history.
      Comprehensive treatment planning with appropriate consultation among the
      restorative dentist and other dental specialists is a prerequisite for a
      successful treatment outcome. This article reviewed the role of orthodontic
      treatment in the restoration of the partially edentulous patient. The case
      illustrations presented show the value of collaborative efforts in a
      multidisciplinary team approach. Although there may be initial reluctance on the
      part of some patients to seek multiple specialty consultations, the rewards are
      great for the patient and the dentists who subscribe to this treatment
      philosophy.

PMID- 8886546
TI  - Surgical-orthodontic correction of adult facial deformities.
AB  - The use of combined surgical-orthodontic therapy for the correction of skeletal
      anomalies has moved from the obscure to the routine over the last 25 years. Its
      use has been extended to treat not only developmental problems in children and
      adolescents, but also traumatic and temporomandibular joint-related deformities
      in adults. Its use can be integrated into a comprehensive treatment plan,
      including prosthodontics, periodontics, and implant dentistry. The advent of
      rigid internal fixation has made it particularly more appealing for the treatment
      of adult patients, allowing the patients to return to normal daily activities
      more rapidly.

PMID- 8886547
TI  - Retention and stability considerations for adult patients.
AB  - This article gives an overview of generally accepted and special concepts of the
      last and often life-long treatment-phase in adult orthodontics, the retention
      phase. The secret of successful adult orthodontics lies in adult-specific
      principles of histology and physiology and the interrelation of joint, occlusion,
      and muscles, which helps define the requirements of proper diagnosis, mechanics,
      and retention. Retention in adults should include maintenance of tooth position,
      overall dental health, and a periodontal status that can be attained by
      combinations of several retention concepts: retention appliances and surgical and
      restorative retention procedures. Short- and long-term postretention follow-up
      studies have shown that there is no guarantee for long-life stability after
      orthodontic tooth movements in adults without an anomaly- and treatment--specific
      retention phase.

PMID- 8886548
TI  - Sex hormones and DHEA-SO4 in relation to ischemic heart disease mortality in
      diabetic subjects. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.
AB  - OBJECTIVE: Sex hormones are associated with atherogenic changes in lipoproteins
      and changes in glucose and insulin metabolism, yet few data are available on the
      relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to
      ischemic heart disease (IHD) in diabetic subjects, a group with very high levels
      of IHD. RESEARCH DESIGN AND METHODS: We examined the relation of total and free
      testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to
      the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin
      Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject
      control design (two control subjects for every diabetic subject). RESULTS: In men
      (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD
      mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total
      testosterone (P = 0.07) predicted IHD mortality. These results were essentially
      unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum
      creatinine, which are major predictors of IHD mortality in the WESDR. Finding
      lower testosterone levels in diabetic subjects of IHD in women is contrary to
      data on risk factors, which suggests that increased androgen activity may be
      associated with worse IHD risk factors. CONCLUSIONS: This study suggests that
      alterations in sex hormones and DHEA-SO4 are unlikely to explain a major
      proportion of the variation in IHD mortality in diabetic subjects.

PMID- 8886549
TI  - An economic analysis of captopril in the treatment of diabetic nephropathy. The
      Collaborative Study Group.
AB  - OBJECTIVE: The results of a recent clinical trial. The Effect of ACE inhibition
      on Diabetic Nephropathy, demonstrated that captopril reduced the rate of renal
      failure, end-stage renal disease (ESRD), and death in patients with IDDM and
      nephropathy. The purpose of this study was to determine the cost-benefit and cost
      effectiveness of captopril as a therapy in patients with IDDM as well as the
      potential savings for all patients with diabetes and nephropathy. RESEARCH DESIGN
      AND METHODS: We used the results from a randomized, placebo-controlled trial
      comparing captopril (207 patients) with placebo (202 patients), whose purpose was
      to determine whether captopril has kidney-protecting properties independent of
      its effect on blood pressure in diabetic nephropathy to develop a model of
      medical treatment for patients before progression to ESRD. To model the course of
      illness after progression to ESRD and to extend the model to patients with NIDDM,
      we used data from the U.S. Renal Data System and published literature. Medical
      resource cost data were based predominantly upon Medicare reimbursement levels,
      published wholesale drug prices, and surveying health care providers. The
      economic model uses a payer perspective to estimate direct cost. The cost to
      society (indirect cost) associated with lost patient productivity due to ESRD was
      also estimated. Using this information, we predicted the costs incurred annually
      and over a lifetime if patients with IDDM and NIDDM and overt nephropathy were
      treated with either placebo or captopril. We also constructed a model of the
      overall prevalence of diabetic nephropathy to estimate the aggregate savings in
      total U.S. health care expenditures. RESULTS: Treatment with captopril resulted
      in an absolute direct cost savings or benefit of $32,550 per patient with IDDM
      over the course of a lifetime compared to treatment with placebo. For patients
      with NIDDM, the direct cost savings totaled $9,900 per patient. Absolute savings
      were found for indirect costs as well: $84,390 per patient with IDDM and $45,730
      per patient with NIDDM. If captopril therapy were initiated in 1995 for patients
      with either IDDM or NIDDM and nephropathy, the aggregate health care cost savings
      (i.e. direct cost savings alone) would be $189 million a year for the year 1999
      and $475 million a year in 2004, the present value of cumulative health care cost
      savings for these 10 years would be $2.4 billion. CONCLUSIONS: The use of
      captopril in diabetic nephropathy will provide significant savings in health care
      costs; in addition, it will result in savings in indirect cost, which reflects
      the broader societal benefit.

PMID- 8886550
TI  - Deranged platelet calcium homeostasis in diabetic patients with end-stage renal
      failure. A possible link to increased cardiovascular mortality?
AB  - OBJECTIVE: Platelet hyperfunction is a typical feature of the prothrombotic state
      that frequently complicates the natural history of diabetes. In uremia, a
      bleeding diathesis is present, which principally involves the primary phase of
      hemostasis. Thus, in patients with uremia of diabetic origin, the infrequent
      coexistence of two opposite alterations of hemostasis takes place. In patients
      with uremia, an increased incidence of cardiovascular events and related
      mortality is observed. This phenomenon is greatly amplified in uremia of diabetic
      origin. Calcium homeostasis is a critical aspect of platelet function, which has
      recently become available in human diseases. The aim of this study was to
      evaluate calcium homeostasis in platelets from patients with uremia of diabetic
      and nondiabetic origin. RESEARCH DESIGN AND METHODS: We evaluated, by means of
      Fura 2, the intracellular concentration of ionized calcium ([Ca2+]i) in platelets
      from 18 patients with uremia of diabetic origin, 12 patients with uremia of
      nondiabetic origin and 16 healthy control subjects [Ca2+]i was evaluated in
      resting conditions and after stimulation with 0.05, 0.1, 0.5 U/ml thrombin.
      RESULTS: Platelets from uremic patients with diabetes had higher resting [Ca2+]i
      than both control subjects (P = 0.01) and uremic patients without diabetes (P =
      0.001). Similarly, after stimulation with thrombin, the absolute increase of
      [Ca2+]i was higher (P < 0.05) in platelets from uremic patients with diabetes
      compared with both control subjects and uremic patients without diabetes. The
      relative increase of [Ca2+]i was higher (P < 0.05) than normal in platelets from
      uremic patients after weak or intermediate strength thrombin. No correlation were
      present between [Ca2+]i values and other clinical and laboratory variables
      potentially associated with platelet hyperfunction. CONCLUSIONS: Diabetes and
      uremia in combination further deteriorate the abnormal platelet calcium
      homeostasis observed in uremia.

PMID- 8886551
TI  - Effect of pregnancy on renal function in patients with moderate-to-severe
      diabetic renal insufficiency.
AB  - OBJECTIVE: Previous studies of patients with diabetic nephropathy and mild renal
      impairment have suggested no determination in renal function as a result of
      pregnancy. The objective of this study was to determine whether pregnancy may
      permanently worsen renal function in women with diabetic nephropathy and moderate
      to-severe renal insufficiency. RESEARCH DESIGN AND METHODS: Eleven patients were
      identified with diabetic nephropathy and moderate-to-severe renal dysfunction
      (creatinine [Cr] > or = 124 mumol/l [1.4 mg/dl]) at pregnancy onset by
      retrospective chart review. Alterations in glomerular filtration rate were
      estimated by using linear regression of the reciprocal of Cr over time. An equal
      number of nonpregnant premenopausal type 1 diabetic women with similar degrees of
      renal dysfunction served as a comparison group for nonpregnant rate of decline of
      renal function and potential contributing factors. RESULTS: Mean serum Cr rose
      from 159 mumol/l (1.8 mg/dl) prepregnancy to 221 mumol/l (2.5 mg/dl) in the third
      trimester. Renal function was stable in 27%, showed transient worsening in
      pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria
      increased in pregnancy in 79%. Exacerbation of hypertension or preeclampsia
      occurred in 73%. Seven patients progressed to dialysis 6-57 months postpartum,
      with 71% (five of seven) of these cases attributed to acceleration of disease
      during the pregnancy. Student's tests and repeated-measures analysis of variance
      support a pregnancy-induced acceleration in the rate of decline of renal
      function. CONCLUSIONS: In this series, patients with diabetic nephropathy and
      moderate-to-severe renal insufficiency were found to have a > 40% chance of
      accelerated progression of their disease as a result of pregnancy.

PMID- 8886552
TI  - Evaluation of delayed gastric emptying in diabetic patients with autonomic
      neuropathy by a new magnetic resonance imaging technique and radio-opaque
      markers.
AB  - OBJECTIVE: Our objective was to validate a new noninvasive magnetic resonance
      imaging (MRI) technique for diagnosis of delayed gastric emptying by using radio
      opaque markers (ROMs) in diabetic patients with and without cardiovascular
      autonomic (CAN) and peripheral sensomotoric neuropathy (PSN). RESEARCH DESIGN AND
      METHODS: Fifteen diabetic outpatients were recruited, eight with CAN and PSN
      (group A, age 28-61 years, mean diabetes duration 27 years) and seven without CAN
      (group B, age 28-60 years, mean diabetes duration 16 years). Gastric emptying and
      motility were assessed with ROMs and MRI in random order. After an overnight fast
      either a test meal (451 kcal) containing a capsule with 10 ROMs is eaten and a
      supine plain abdominal X ray is taken after 6 h or 500 ml intralipid 10% (550
      kcal) is swallowed for the MRI study, using a 1.5 Tesla Gyroscan ACS II (Philips,
      Eindohoven, The Netherlands). Computer-assisted segmentation of images was used
      to measure gastric emptying (T1/2, min) over 125 min, contraction frequency (F,
      min-1), mean contraction amplitude (CA, % basal), and velocity (V, cm/s). Blood
      glucose was kept constant at 5.0-8.0 mmol/l. RESULTS: In group A, 6.1 +/- 1.36
      ROMs (mean +/- SE) were retained in the stomach after 6 h and 0 ROM in group B,
      indicating a significant delay of gastric emptying in patients with CAN. The MRI
      study revealed a significantly longer gastric emptying (P < 0.005) in group A
      (T1/2 = 124 +/- 10 min) as compared with group B (T1/2 = 85 +/- 18 min). There
      was no difference in F, CA, and V between the two groups: F 2.9 +/- 0.07 and 2.7
      +/- 0.1 (min-1), CA 26.8 +/- 1.2 and 29.6 +/- 1.6 (% basal), V 0.43 +/- 0.02 and
      0.40 +/- 0.02 (cm/s), respectively. CONCLUSIONS: MRI offers the possibility of
      visualizing and examining exactly the mechanisms responsible for gastric emptying
      and is characterized by a high specificity but a lower sensitivity as compared
      with ROMs, which proved to be an ideal screening test for diagnosis of
      gastroparesis in clinical practice.

PMID- 8886553
TI  - Demonstration of regional sympathetic denervation of the heart in diabetes.
      Comparison between patients with NIDDM and IDDM.
AB  - OBJECTIVE: Global myocardial uptake of 123I-metaiodobenzylguanidine (MIBG) has
      been shown to be decreased in diabetic patients with autonomic neuropathy,
      indicating cardiac sympathetic dysfunction. However, possible differences in
      myocardial MIBG distribution between NIDDM and IDDM diabetic patients are not
      known. RESEARCH DESIGN AND METHODS: Regional myocardial distribution of 123I-MIBG
      was studied in seven male IDDM patients (age 45 +/- 2 years, duration of diabetes
      30 +/- 3 years, means +/- SE) and 13 NIDDM patients (8 men, 5 women, age 59 +/- 2
      years, duration of diabetes 10 +/- 1 years). A dual-tracer single-photon emission
      tomography was carried out with 123I-MIBG and 99mTc-methoxyisobutylisonitrrile to
      asses simultaneously myocardial sympathetic innervation and perfusion at rest.
      Conventional autonomic nervous function tests, power spectral analysis of heart
      rate variability, and echocardiography were performed for assessments of
      autonomic function and cardiac dimensions and function. RESULTS: Autonomic
      nervous function tests and echocardiography showed similar results in IDDM and
      NIDDM patients. Despite this, global myocardial MIBG uptake (0.43 +/- 0.04 vs.
      0.59 +/- 0.06, P = 0.03) and MIBG heart-to-liver ratio (0.59 +/- 0.03 vs. 0.68 =
      0.03, P = 0.05) were lower in NIDDM compared with IDDM patients. Regional
      distribution of MIBG uptake and regional MIBG/perfusion ratio revealed
      significantly reduced uptake in NIDDM patients especially in the inferoposterior
      segments of the left ventricle compared with IDDM patients. Difference in age
      between NIDDM and IDDM patients did not explain the results. CONCLUSIONS: Reduced
      myocardial MIBG uptake was found in NIDDM patients compared with the uptake in
      IDDM patients, particularly involving inferoposterior segments. Regional
      sympathetic damage not detectable with conventional autonomic function tests is
      relatively common in NIDDM.

PMID- 8886554
TI  - The efficacy of tolrestat in the treatment of diabetic peripheral neuropathy. A
      meta-analysis of individual patient data.
AB  - OBJECTIVE: The aim of this meta-analysis was to review the existent evidence on
      the effectiveness of tolrestat in the treatment of diabetic peripheral
      neuropathy. RESEARCH DESIGN AND METHODS: Individual patient data on 738 subjects
      from the three randomized clinical trials published on this topic were analyzed
      using changes in motor nerve conduction velocities (NCVs) as endpoints. Nerves
      investigated included median, ulnar, tibial, and peroneal. RESULTS: The pooled
      analysis of NCV taken as a continuous measurement showed a significant treatment
      effect, the magnitude of this benefit being approximately equal to 1 m/s for all
      the nerves investigated. When looking at the proportion of patients experiencing
      a loss of NCV of at least 1 or 2 m/s in at least two out of the four nerves
      investigated, it emerged that treatment reduced by > 40% the risk of such
      outcomes after adjusting for patients' characteristics. The odds ratios relative
      to the placebo group were 1.82 (1.30-2.52) and 1.70 (1.15-2.48) for a decrease of
      1 and 2 m/s, that is, placebo-treated patients have an 82 and 70% increased risk
      for a loss of nerve function of 1 and 2 m/s, respectively. No statistically
      significant difference in treatment effect emerged after stratification according
      to baseline motor NCV and glycated hemoglobin levels. CONCLUSIONS: After a
      treatment duration ranging between 24-52 weeks, patients treated with tolrestat
      had a reduced risk for developing nerve function loss compared with placebo
      treated patients. Future long-term trials are needed to evaluate the impact of
      the treatment on more clinically meaningful endpoints such as the development of
      foot complications.

PMID- 8886555
TI  - Depression and risk for onset of type II diabetes. A prospective population-based
      study.
AB  - OBJECTIVE: To determine whether depression is associated with an increased risk
      for onset of diabetes. RESEARCH DESIGN AND METHODS: In 1981, a total of 3,481
      household-residing adults participated in the Epidemiologic Catchment Area (ECA)
      Program survey at the East Baltimore site. A follow-up of that cohort after 13
      years completed 1,897 interviews, amounting to > 72% of survivors. In 1981,
      depression was assessed with the National Institutes of Mental Health (NIMH)
      Diagnostic Interview Schedule and diabetes, by self-report. This prospective
      analysis focused on subjects at risk for onset of diabetes by removing from the
      analysis individuals with diabetes in 1981. RESULTS: There were 89 new cases of
      diabetes among 1,715 individuals at risk, yielding a 13-year cumulative incidence
      of diabetes of 5.2%. In logistic models, major depressive disorder, but not
      milder forms of depression or other forms of psychiatric disorder, predicted the
      onset of diabetes (estimated relative risk, 2.23; 95% CI 0.90-5.55). Controlling
      for age, race, sex, socioeconomic status, education, use of health services,
      other psychiatric disorders, and body weight did not weaken the relationship.
      CONCLUSIONS: Major depressive disorder signals increased risk for onset of type
      II diabetes. Limitations of the findings arise from the difficulty in determining
      temporal order with two chronic conditions, even when the temporal order of
      measurement is clear. In addition, even though control variables were introduced
      for the use of health services, it is possible that the treatment for depression
      led to an earlier diagnosis of diabetes in this sample.

PMID- 8886556
TI  - LDL apheresis reduces the susceptibility of LDL to in vitro oxidation in a
      diabetic patient with hemodialysis treatment.
AB  - OBJECTIVE: We studied whether LDL apheresis would alter the susceptibility of LDL
      to in vitro oxidative modification induced by copper ion in a diabetic patient
      undergoing hemodialysis treatment. RESEARCH DESIGN AND METHODS: Isolated LDL was
      dialyzed against phosphate-buffered saline and resuspended at a concentration of
      0.3 mg cholesterol mass/ml buffer LDL oxidation was then initiated by addition of
      1.66 mumol/l CuSO4, and the formation of conjugated dienes was continuously
      monitored spectrophotometrically at 234 nm. RESULTS: The duration of the lag
      phase of LDL obtained after LDL apheresis was markedly longer than that of LDL
      obtained before LDL apheresis. The propagation rate and the maximum conjugated
      diene formation of LDL oxidation were not changed after LDL apheresis.
      CONCLUSIONS: A LDL subfraction that was susceptible to oxidation was removed by
      LDL apheresis, resulting in reduction of susceptibility of LDL to in vitro
      oxidation remaining in plasma. LDL apheresis may be of clinical importance for
      preventing atherosclerotic disease in diabetic patients undergoing hemodialysis.

PMID- 8886557
TI  - Differing effects of pancreas-kidney transplantation with systemic versus portal
      venous drainage on cholesteryl ester transfer in IDDM subjects.
AB  - OBJECTIVE: Cholesteryl ester transfer (CET) is accelerated in patients with IDDM
      treated with conventional (subcutaneous) insulin therapy (CIT) and a number of
      other disorders associated with premature cardiovascular disease. We have shown
      that in IDDM this disturbance is closely linked to iatrogenic hyperinsulinemia
      (HI), because it was reversed when insulin was administered by the intraportal
      (i.p.) route. In this study, we sought to determine whether HI after successful
      pancreas-kidney transplantation (PKT) has the same adverse effect on CET.
      RESEARCH DESIGN AND METHODS: CET was measured by both mass and isotopic assays
      and compared in two groups of euglycemic non-insulin-requiring IDDM PKT patients
      with either systemically draining allografts and persistent HI or grafts with
      portal vein anastomoses that were normoinsulinemic (PK-P). A third group of eight
      nondiabetic kidney transplant (KT) patients receiving the same immunosuppressive
      drugs served as control subjects. RESULTS: CET in pancreas-kidney transplantation
      subjects with systemic venous drainage (PK-S) was increased (P < 0.001) to the
      same level we have reported previously in IDDM patients receiving CIT and was
      significantly higher (P < 0.001) than in those subjects with PK-P. CET in the PK
      P group did not differ from that of the KT control patients. CONCLUSIONS: CET is
      affected by variations in systemic insulin levels in pancreas transplant patients
      with allografts that have differing venous drainage. Because high systemic
      insulin levels are linked to the activation of (ET, euglycemic HI IDDM pancreas
      allograft recipients may continue to be at high risk for macrovascular
      complications.

PMID- 8886558
TI  - Elevated plasma levels of transforming growth factor-beta 1 in NIDDM.
AB  - OBJECTIVE: Transforming growth factor-beta (TGF-beta) is a potent inducer of
      extracellular matrix production and of fibrogenesis and has been associated with
      the occurrence of diabetic micro- and macrovascular complications. Our aim was to
      determine whether circulating levels of TGF-beta 1 are altered in NIDDM and, if
      so, whether they are correlated with blood glucose and show an association with
      diabetic complications. RESEARCH DESIGN AND METHODS: Plasma levels of TGF-beta 1
      were determined by enzyme-linked immunosorbent assay in 44 NIDDM patients and 28
      control subjects of comparable age and weight and were correlated with parameters
      of metabolic control and the occurrence of micro- and macrovascular
      complications. RESULTS: TGF-beta 1 was significantly elevated in NIDDM (7.9 +/-
      1.0 ng/ml), as compared with control subjects (3.1 +/- 0.4 ng/ml, P < 0.001) and
      correlated with glycosylated hemoglobin (r2 = 0.42; P < 0.001). Thrombocyte
      levels of TGF-beta 1 were similar in control subjects (54 +/- 7 pg/ml, n = 16)
      and diabetic patients (61.6 +/- 18 pg/ml, n = 13; P = 0.357). Elevated TGF-beta 1
      levels were associated with retinopathy and neuropathy. CONCLUSIONS: We conclude
      that plasma levels of TGF-beta 1 are elevated in NIDDM patients and may be
      related to average blood glucose. Preliminary data suggest that they may
      contribute to the occurrence of diabetic complications.

PMID- 8886559
TI  - Relationship of locus of control to physical activity among people with and
      without diabetes.
AB  - OBJECTIVE: To examine the relationship between locus of control (LOC) (internal
      and external) and physical activity in Pima Indians and to determine whether this
      relationship is affected by the presence of diabetes. RESEARCH DESIGN AND
      METHODS: A population-based sample of 580 Pima Indians was recruited from an
      ongoing research study. LOC was measured on a 1-40 modified Rotter scale, and
      past year total physical activity (leisure and work physical activity levels
      combined) was measured by interviewer-administered questionnaire. RESULTS: Among
      both men and women without diabetes, individuals with an internal LOC (score 1
      16) were significantly (P < 0.01) more active than those with an external (score
      17-40) LOC (70 vs. 30 median metabolic equivalent [MET] hours per week for men:
      12 vs. 5 median MET hours per week for women). Controlled for age and BMI, an
      internal LOC was significantly associated with a higher level of physical
      activity among men (P = 0.04) and women (P = 0.001) without diabetes, but not
      among those with diabetes. CONCLUSIONS: Nondiabetic Pima Indians with an internal
      LOC are more physically active than those with an external LOC. Enhancing
      perceptions of internal control may influence physical activity and thus have
      implications for diabetes prevention.

PMID- 8886560
TI  - Hypertriglyceridemia enhances monocyte binding to endothelial cells in NIDDM.
AB  - OBJECTIVE: The mechanisms by which diabetes leads to rapidly progressive
      atherosclerosis are not fully understood. Adherence of monocytes to the arterial
      wall is an early event in the development of atherosclerotic lesions. RESEARCH
      DESIGN AND METHODS: The binding of freshly isolated monocytes from patients with
      NIDDM, IDDM, and healthy control subjects to a monolayer of endothelial cells
      obtained from human umbilical vein was investigated. RESULTS: Endothelial
      adherence of monocytes from normolipidemic patients with IDDM (15.8 +/- 4.5%) or
      NIDDM (16.9 +/- 4.6%) was comparable to that of monocytes from a control
      population (15.3 +/- 3.5%). In patients with NIDDM with a serum triglyceride
      concentration > 2.5 mmol/l, the percentage of cells that adhere to endothelial
      cells in vitro was significantly increased (23.3 +/- 3.1%). Glycemic control did
      not correlate with monocyte adherence. The presence of symptomatic
      atherosclerotic disease, age, or sex was not associated with a change in monocyte
      binding in vitro. CONCLUSIONS: The results suggest that in NIDDM
      hypertriglyceridemia should be treated to reduce the high risk for
      atherosclerosis.

PMID- 8886561
TI  - A population-based study of the prevalence of diabetes and impaired glucose
      tolerance in adults in northern Sudan.
AB  - OBJECTIVE: To study the prevalence of glucose intolerance in adult urban and
      rural populations in the northern parts of Sudan. RESEARCH DESIGN AND METHODS: A
      sample of 1,284 subjects aged > or = 25 years was selected using a multistage
      cluster method and underwent a 75-g oral glucose tolerance test. RESULTS: The
      crude prevalence was 3.4% (men, 3.5%; women, 3.4%) for diabetes and 2.9% (men,
      2.2%; women, 3.3%) for impaired glucose tolerance (IGT). The highest crude
      prevalence was in the northern parts of Sudan (5.5%) and the lowest in the
      western desert-like parts (0.9%). Diabetes and IGT rates were not different
      between the urban and rural populations. New cases (2.2%) were almost twice as
      prevalent as previously known cases (1.3%). Family history of diabetes, obesity,
      and advanced age were associated with higher rates of diabetes. CONCLUSION: The
      results showed a high prevalence of diabetes in the adult population of Sudan,
      with a wide difference among the different areas. The high ratio of newly
      discovered to previously known diabetic cases may reflect poor public awareness
      and medical services. These findings will certainly have far-reaching
      implications for diabetes care delivery in this country.

PMID- 8886562
TI  - Lipoprotein (a) levels in African-Americans with NIDDM.
AB  - OBJECTIVE: The purpose of this study was to investigate possible relationships
      between lipoprotein (a) [Lp(a)] levels and NIDDM in African-Americans. The
      objectives were to identify associations between Lp(a) levels of subjects with
      and without NIDDM and to determine the influence of glycemic control, determined
      by GHb, and of mode of therapy on Lp(a) levels. RESEARCH DESIGN AND METHODS: We
      studied [4] African-American subjects, 103 with NIDDM and 38 without NIDDM. Their
      Lp(a) levels, GHb levels, and apolipoprotein (a) [apo(a)] isoforms were
      determined. Clinical information, including mode of therapy (sulfonylurea,
      insulin, or no pharmacological therapy), date of diagnosis, and medical history,
      was obtained by chart review and patient interview. RESULTS: There was no
      significant difference in median Lp(a) levels between the non-NIDDM (25.5 mg/dl)
      and NIDDM (24.0 mg/dl) study subjects. No statistically significant difference
      was found in Lp(a) levels when NIDDM patients with GHb < 12.3% were compared to
      those with GHb > or = 12.3% (P = 0.096). An inverse relationship was found
      between apo(a) root-mean-square isoform size and Lp(a) level (r2 = 0.091, P =
      0.0035). Analysis of the cases by mode of therapy indicates that there is
      evidence of an increased median level of Lp(a) in African-Americans with NIDDM on
      insulin therapy relative to those on sulfonylurea (34.0 vs. 16.0 mg/dl; P =
      0.013) and to nondiabetic subjects (34.0 vs. 25.5 mg/dl; P = 0.043). CONCLUSIONS:
      We conclude that the level of plasma Lp(a) is higher in African-Americans with
      NIDDM who are being treated with insulin when compared to those on sulfonylurea
      therapy and to those who are non-NIDDM subjects, and this does not seem to be due
      to genetic variance or method bias.

PMID- 8886563
TI  - Thrombolytic therapy in diabetic patients with acute myocardial infarction.
AB  - OBJECTIVE: To compare the frequency of thrombolytic therapy in diabetic and
      nondiabetic patients with acute myocardial infarction (MI) and to examine why
      some diabetic patients do not receive thrombolytic therapy. RESEARCH DESIGN AND
      METHODS: Retrospective study of all diabetic patients with acute MI admitted to
      the coronary care unit of Aalborg Hospital within a 3-year period. RESULTS: Only
      35% (43 of 123) of patients with diabetes compared with 47% (404 of 856) of
      patients without diabetes received thrombolytic therapy (P < 0.002). There was no
      difference in the percentage of patients thrombolyzed among patients admitted to
      the hospital within 12 h after onset of symptoms. Of diabetic patients who were
      not thrombolyzed, 60% (48 of 80) arrived at the hospital later than 12 h after
      onset of symptoms. Among patients who arrived late, 63% (35 of 56) had Q wave
      infarction and 84% (47 of 56) had symptoms typical of acute MI. Mortality was 29%
      (16 of 56) in this group. Only one patient did not receive thrombolytic therapy
      due to diabetic retinopathy. CONCLUSIONS: Significantly fewer diabetic patients
      received thrombolytic therapy compared with patients without diabetes. The main
      reason diabetic patients did not receive thrombolytic therapy was late arrival to
      the hospital.

PMID- 8886564
TI  - A prospective analysis of the HOMA model. The Mexico City Diabetes Study.
AB  - OBJECTIVE: Both insulin resistance (IR) and decreased insulin secretion have been
      shown to predict the development of NIDDM. However, methods to assess insulin
      sensitivity and secretion are complicated and expensive to apply in
      epidemiological studies. The homeostasis model assessment (HOMA) has been
      suggested as a method to assess IR and secretion from the fasting glucose and
      insulin concentrations. RESEARCH DESIGN AND METHODS: We applied the HOMA model in
      the 3.5-year follow-up of the Mexico City Diabetes Study. RESULTS: Out of 1,449
      subjects, 97 developed diabetes. When modeled separately insulin resistance but
      not insulin secretion predicted NIDDM. However, when both variables were entered
      into the same regression model, both increased IR and decreased beta-cell
      function significantly predicted NIDDM. CONCLUSIONS: We conclude that the HOMA
      provides a useful model to assess beta-cell function in epidemiological studies
      and that it is important to take into account the degree of IR in assessing
      insulin secretion.

PMID- 8886565
TI  - High-fat and high-carbohydrate diets and energy balance.
AB  - The current American Diabetes Association guidelines for nutrition recommend a
      moderate increase in monounsaturated fats and a reduced intake of carbohydrate in
      patients with diabetes in whom high-carbohydrate diets deteriorate glycemic
      control and lipoprotein levels. High-fat diets, however, are believed to promote
      obesity, and some investigators may have reservations recommending such diets.
      This review thus investigates the role of diet composition in promoting obesity
      or achieving weight loss and its implications in patients with diabetes.
      Epidemiological studies show some evidence that fat intake is more importantly
      related to body weight than carbohydrate intake, but conclusions are weak because
      confounding variables, such as physical activity, smoking, and energy intake,
      were generally not controlled for. Metabolic studies under isoenergic conditions
      report no change in energy balance when fat intake is increased, but report a
      negative fat balance with substantial increase carbohydrate intake. During
      overfeeding, excess fat intake is stored as fat, whereas excess carbohydrate is
      mostly oxidized in the short term but can lead to substantial gain in fat stores
      because of reduced fat oxidation and considerable de novo lipogenesis in the long
      term. Spontaneous energy intake, however, is higher on an unrestricted high-fat
      diet compared with a high-carbohydrate diet, but the long-term effects are not
      known. Weight-loss intervention studies show that a hypocaloric high-carbohydrate
      diet is not associated with more weight loss than a high-fat hypocaloric diet. In
      conclusion, a high-monounsaturated fat diet to control glycemic control and
      lipoprotein levels in patients with diabetes should not affect weight loss or
      maintenance, provided that energy intake is carefully controlled.

PMID- 8886566
TI  - The role of patient participation in the doctor visit. Implications for adherence
      to diabetes care.
AB  - For patients, treatment of diabetes involves complex changes in basic behaviors
      and adherence to complicated regimens. Understanding the factors that enable
      patients to adhere to diabetes treatment is the first step to designing effective
      interventions. Researchers of diabetes care have postulated that increasing
      diabetic patients' participation in medical decision making during the doctor
      visit is likely to improve their adherence to self-care. However, a critical
      review of the impact of patient participation on diabetic patients adherence to
      self-care is absent from the literature. We review the subject of patient
      participation in medical decision making and its effect on adherence to self-care
      for patients with diabetes. We introduce a model of the determinants of adherence
      to diabetes self-care that incorporates the effects of patient participation in
      medical decision making. In this model, we suggest three ways that patient
      participation can affect adherence to self-care: 1) it may have a direct effect;
      2) it may affect adherence to self-care indirectly by affecting patients'
      understanding of their treatment regimen or the fit of their regimen with their
      lifestyle; and 3) perceived omissions of participation can affect adherence to
      self-care indirectly through an effect on patient satisfaction. Research is
      needed to identify more clearly which components of patient participation affect
      adherence to self-care and in what ways. Distinguishing patient and physician
      behaviors that contribute to the process of patient participation would provide a
      means to develop specific behavioral interventions.

PMID- 8886568
TI  - Are research and policy advocacy two separate worlds?

PMID- 8886567
TI  - Erythrocyte and plasma antioxidant activity and subclinical complications in
      young diabetic patients.

PMID- 8886569
TI  - Mitochondrial gene abnormalities and alpha- and beta-cell dysfunction.

PMID- 8886570
TI  - American Diabetes Association annual meeting 1996: managed care and change in
      medicine.

PMID- 8886571
TI  - Solitary views of the stomach.
AB  - Technology has propelled gastric physiology and pathophysiology since 1825, the
      year when the French Academy of Science tried to attribute a prize to the best
      paper on digestive physiology. I have analyzed the contributions of Ismar Boas,
      as well as my personal experience in studying gastric mucosal permeability,
      gastric secretion, a vaccine directed against Helicobacter pylori and the
      metabolism of this pathogen. In addition, I have examined the interplay between
      sociopolitical events and research activities, the role of suppressed minorities
      in research, the falacies of falsification strategies, the dependence of valid
      results from unorthodox experimental approaches and creative elements. Some of
      the older gastric researchers expressed solitary views-an attitude which may have
      helped them to make novel and valid observations.

PMID- 8886572
TI  - Significance of ammonia in the genesis of gastric epithelial lesions induced by
      Helicobacter pylori: an in vitro study with different bacterial strains and urea
      concentrations.
AB  - Two Helicobacter pylori products cause cell damage both in vivo and in vitro:
      ammonia, from bacterial urease activity, and a vacuolating toxin named VacA. In
      this in vitro study, the vacuolating effect of H. pylori broth culture filtrate
      from a VacA-positive/urease-positive strain is compared with that of a VacA
      negative/urease-positive strain and a VacA-negative/urease-negative strain. The
      effect of VacA and ammonia was evaluated with and without addition of 10 mM urea,
      a physiological concentration for the human stomach, and with and without
      addition of 0.5 mg/ml acetohydroxamic and (AHA), an urease inhibitor. Our data
      show that: (1) both urease-positive H. pylori strains caused cell vacuolation in
      the absence of urea, the VacA-positive strain being approximatively twice as
      potent as the VacA-negative strain; (2) addition of urea to the culture medium
      caused an approximatively 3-fold increase in the vacuolating activity of both
      urease-positive strains; (3) a VacA-negative/urease-negative strain did not exert
      any vacuolating effect, either in the presence or in the absence of urea; (4) the
      ratio between cell vacuolation induced by VacA-positive and VacA-negative strains
      was enhanced by the presence of AHA: ratio was about 2 in the absence of AHA and
      about 6 in the presence of AHA, either with or without urea added. The increment
      of vacuolation is likely due to an interaction between AHA and VacA. In
      conclusion, a VacA-negative/urease-positive strain becomes highly cytotoxic when
      physiological levels of urea are present in the incubation medium. This finding
      suggests that all urease-positive H. pylori strains, both with and without VacA
      expression, should be considered as potentially cytotoxic for the human gastric
      mucosa, although VacA enhances the severity of cell damage.

PMID- 8886573
TI  - Helicobacter pylori-negative duodenal and pyloric ulcer: role of NSAIDs.
AB  - To investigate the frequency of use of nonsteroidal anti-inflammatory drugs
      (NSAID) in duodenal or pyloric ulcer patients who do not have Helicobacter pylori
      gastritis, we retrospectively analyzed the use of these drugs among 16 patients
      who had an endoscopically diagnosed duodenal or pyloric ulcer but had a
      histologically normal and noninfected stomach, and compared this frequency of use
      of NSAIDs with that in three control groups. The 16 patients are a consecutive
      subgroup (2.3%) from 707 patients who were endoscopically diagnosed as having
      duodenal or pyloric ulcer in Jorvi Hospital during 1985-1994. In all 16 patients,
      endoscopical and clinical appearances of the ulcers were seen by the clinician
      similar to those in ordinary peptic ulcer disease. The ulcers occurred at the
      same site in the duodenal bulb and pylorus as the ordinary peptic ulcers but
      tended to bleed more often: endoscopy was done more frequently among the 16
      gastritis-negative patients because of ulcer bleeding than among the controls.
      Thirteen of the 16 patients (81%; CI95: 62-100%) did use NSAIDs. This frequency
      was higher (p < 0.05) than the corresponding frequency of the use of NSAIDs in
      any of the three control groups, i.e. (a) H. pylori-positive duodenal or pyloric
      ulcer patients [16 of 39 (41%)], (b) H. pylori-negative nonulcer patients [11 of
      64 (17%)] or (c) H. pylori-positive nonulcer patients [14 of 42 (33%)]. We
      conclude that the history of use of NSAIDs is more common in duodenal and pyloric
      ulcer patients who have a normal, noninfected stomach than the history of use of
      NSAIDs in those in whom the ulcer is associated with H. pylori gastritis.

PMID- 8886574
TI  - Evidence for a regulatory role for histamine in gastric enterochromaffin-like
      cell proliferation induced by hypergastrinemia.
AB  - BACKGROUND/AIMS: Hypergastrinemia, induced by sustained suppression of gastric
      acid secretion, is associated with gastric enterochromaffin-like (ECL) cell
      hyperplasia and carcinoid tumor formation. We examined the effect of a selective
      H1-histamine antagonist, terfenadine, on gastric mucosal cell proliferation to
      determine whether histamine might modulate ECL cell generation. METHODS: The
      rodent mastomys received the H2-antagonist loxtidine (2 g/l drinking water) alone
      or in combination with terfenadine (0.5 g/l or 35 mg/l drinking water) for 120
      days. Controls received water or terfenadine alone. Serum gastrin levels and
      tissue histamine content were assayed by radioimmunoassays, and tissue
      chromogranin levels determined (Western blot analysis). In vivo cell
      proliferation was measured by bromodeoxyuridine (BrdU, 200 mg/kg/day, 3 days)
      incorporation. Gastric mucosal thickness was determined, ECL cell number was
      assessed, and the percentage of proliferating ECL cells quantitated. To evaluate
      the direct action on ECL cells we then studied the effect of terfenadine on
      histamine secretion and DNA synthesis (BrdU uptake) in an isolated preparation
      (approximately 90% pure) of ECL cells. RESULTS: Loxtidine increased serum gastrin
      levels, mucosal thickness, tissue chromogranin levels, tissue histamine content,
      BrdU incorporation, ECL cell number, and proliferating ECL cells (all parameters
      p < 0.05). Terfenadine alone, irrespective of dosage, had no significant effect.
      The high dose in combination with loxtidine significantly inhibited the increase
      in tissue chromogranin levels, tissue histamine content, ECL cell number and
      proliferating ECL cells (p < 0.05), but did not alter other parameters, compared
      to loxtidine alone. The low does did not alter the loxtidine-induced changes. In
      pure isolated ECL cells, terfenadine did not alter histamine secretion either
      alone or in combination with gastrin (10 nM). DNA synthesis was significantly
      inhibited by terfenadine (IC50 10(-10) M). CONCLUSIONS: Terfenadine specifically
      inhibited the effect of loxtidine-induced ECL cell proliferation in vivo and
      significantly inhibited ECL cell DNA synthesis in vitro. We postulate that
      histamine, through an H1 receptor, positively modulates gastric ECL cell
      proliferation.

PMID- 8886575
TI  - Role of prostaglandins and calcitonin gene-related peptide in central vagal
      cholinergic-dependent protection against gastric injury in urethane-anesthetized
      rats.
AB  - The influence of central vagal activation induced by the thyrotropin-releasing
      hormone (TRH) analog, RX 77368, injected intracisternally on gastric mucosal
      injury produced by 60% ethanol (4 ml.kg-1) was investigated in urethane
      anesthetized rats. RX 77368 (3, 10 and 30 ng) inhibits dose dependently
      macroscopic gastric damage induced by intragastric administration of 60% ethanol
      by 18, 43 and 77%, respectively. The cytoprotective effect of intracisternal RX
      77368 (30 ng) was completely blocked by cervical vagotomy, atropine (2 mg.kg-1
      s.c.), and CGRP8-37 (100 micrograms.kg-1 i.v.) and partially inhibited by
      indomethacin (5 mg.kg-1 i.p.). Vagotomy, atropine, indomethacin and CGRP8-37
      alone did not modify gastric mucosal lesions induced by ethanol in rats injected
      intracisternally with saline. The present data show that intracisternal injection
      of TRH analog in urethane-anesthetized rats protects against ethanol-induced
      gastric injury through vagal cholinergic dependent pathways which recruit
      prostaglandins and CGRP mechanisms.

PMID- 8886576
TI  - Erythropoietin stimulates proliferation of rat-cultured gastric mucosal cells.
AB  - Most anemic patients with chronic renal failure have gastric mucosal lesions.
      However, these gastric lesions are often improved after the administration of
      recombinant human erythropoietin (rHuEPO). We have used the rat gastric mucosal
      cell line RGM-1, to examine the possibility that rHuEPO might directly stimulate
      the growth of gastric mucosal cells in vitro. Our results show that rHuEPO dose
      dependently increased [3H]thymidine incorporation into RGM-1 cells and their
      expression of c-myc gene. In addition, 125I-rHuEPO specifically bound to RGM-1
      cells, and moreover, erythropoietin receptor gene expression was detected by RT
      PCR. We conclude that rHuEPO has a direct growth-promoting effect on RGM-1 cells,
      suggesting possible usefulness of rHuEPO administration for the treatment of
      gastric mucosal damage in patients with chronic renal failure.

PMID- 8886577
TI  - Regulation of mouse pancreatitis-associated protein-I gene expression during
      caerulein-induced acute pancreatitis.
AB  - The pancreatitis-associated proteins (PAPs) are major pancreatic secretory
      proteins during acute pancreatitis. However, mechanisms of regulation of PAP gene
      expression are poorly understood, and there is a lack of information regarding
      mouse PAP gene expression. Herein, we employed Northern blotting and RNase
      protection assays to measure mouse PAP-I mRNA levels in the normal pancreas and
      intestine, and in the pancreas during caerulein-induced acute pancreatitis.
      Unexpectedly, we found that mouse PAP-I mRNA levels are constitutively high in
      the adult pancreas, as well as in the small intestine. Furthermore, mouse
      pancreatic PAP-I mRNA levels are rapidly and dramatically down-regulated (3 h)
      after the initiation of caerulein injections, but slowly return to high levels by
      72 h. Interestingly, we found that pancreatic PAP-I mRNA levels are also
      transiently and dramatically down-regulated after L-buthionine-[S,R]-sulfoximine
      administration. Thus, a correlation between PAP-I mRNA levels and glutathione
      levels in the mouse pancreas was demonstrated.

PMID- 8886578
TI  - Regulation of motilin release from isolated perfused pig duodenum.
AB  - The release of motilin from an isolated preparation of pig duodenum has been
      studied. There different types of stimuli were applied: electrical nerve
      stimulation, intraarterially administered peptides, and instillation of test
      solutions into the lumen of the duodenum. Furthermore extracts of 20 different
      regions of the pig digestive system have been analyzed for motilin content.
      Analysis of the extracts only detected significant presence of motilin in the pig
      duodenum and jejunum (79 +/- 15 and 60 +/- 19 pmol/g). The stimulation
      experiments showed: (1) a significant noncholinergic depression of motilin
      release during electrical stimulation of the vagus nerve (nadir at 74 +/- 5% of
      baseline level; (2) a significant elevation of motilin release in response to
      intraarterially administered vasoactive intestinal peptide (VIP) (peak at 330 +/-
      35% of baseline level), and (3) a significantly elevated motilin release in
      response to instillation of autologuous bile (peak at 170 +/- 16% of baseline
      level) and hydrochloric acid (peak at 196 +/- 42% of baseline level) into the
      duodenal lumen. In conclusion, luminal acidification and bile are important
      factors in stimulation of motilin release, whereas the vagally stimulated VIP
      release was insufficient to overcome the general inhibitory effect of vagus
      stimulation.

PMID- 8886579
TI  - Studies on the viability of the isolated vascularly perfused rat colon.
AB  - The colon contains large numbers of endocrine cells. Insight into their
      physiological function is limited. This is due to the fact that no sufficient
      model of isolated endocrine colon cells is available. In the present study we
      introduce an isolated vascularly perfused colon model for in vitro studies. This
      model offers the advantage that it keeps the endocrine cells in their
      physiological orientation and environment. The gut mucosa is highly sensitive to
      ischemia. Therefore, a careful validation of its viability is crucial in gut
      organ preparations. This study demonstrates that, by utilizing an oxygenated
      vascular medium supplemented with 25% washed bovine erythrocytes, a perfusion of
      the colon is achieved for at least 1 h without obvious tissue injuries. During
      this time parameters such as perfusion pressure, venous lactate dehydrogenase
      release, glucose consumption, lactate output, oxygen consumption, perfusate loss
      by the preparation and morphology were analyzed. Dependent on stimulation, the
      endocrine L cells of the colon released glucagon-like peptide-I upon arterial
      perfusion of methacholine or gastrin-releasing peptide. In conclusion, a model
      for the isolated perfusion of the colon is introduced which is suitable for
      studies of endocrine colon cells.

PMID- 8886580
TI  - Hepatic and intestinal elimination of endogenous gastrin in pigs.
AB  - The elimination of endogenous carboxyamidated and glycine-extended gastrins in
      liver and gut was studied before and after feeding in 14 anesthetized pigs.
      Before the meal, liver and gut extractions were nonsignificant. After feeding,
      the release rate of amidated gastrin increased from 7.5 +/- 2.6 to 21.9 +/- 5.3
      pmol/min (p < 0.02), and the liver extracted significant amounts of amidated
      gastrin, while the intestinal extraction remained nonsignificant. The
      postprandial hepatic extraction ratio increased from 0.09 +/- 0.04 to 0.18 +/-
      0.04 (p < 0.01). Before feeding, the hepatic and extrahepatic clearance rates
      were 80.0 +/- 38.7 and 232.3 +/- 77.7 ml/min. Clearance rates after feeding were
      144.8 +/- 29.5 (p < 0.01) and 326.4 +/- 75.3 ml/min (NS), respectively. Portal
      plasma displayed a small postprandial increase in the concentration of glycine
      extended gastrin, but extraction over the liver and gut remained nonsignificant.
      Gel chromatography of portal plasma showed that the fraction of postprandial
      amidated gastrin corresponded to gastrin-17. The concentration of glycine
      extended gastrin was too low for chromatographic analysis. We conclude that
      endogenous amidated gastrin is eliminated in the liver after feeding in pigs.

PMID- 8886581
TI  - Comparison of the effects of transforming growth factor alpha and epidermal
      growth factor on gastrointestinal proliferation and hormone release.
AB  - Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha)
      bind to a common receptor and are both present in the normal gastrointestinal
      tract. Although many studies have examined their function in isolation, there is
      little information directly comparing their actions. We examined the relative
      potency of TGF alpha and EGF in stimulating 3H-thymidine uptake into primary rat
      hepatocytes at various doses in vitro and on the crypt cell production rate
      (CCPR) within the gastrointestinal tract when infused intravenously at 49
      nmol/kg/day into rats receiving total parenteral nutrition. In vitro, maximal
      stimulatory activity was similar in EGF- and TGF alpha-treated cells, however,
      the dose of EGF required to stimulate 3H-thymidine uptake to 50% of maximal
      levels was only one third of that required using TGF alpha. In vivo, EGF and TGF
      alpha significantly increased the weight and proliferative indices throughout the
      gastrointestinal tract. The response (as determined by CCPR) was about 80% higher
      in animals which had received EGF when compared to animals receiving TGF alpha.
      Treatment with EGF also caused significant rises in plasma PYY, enteroglucagon
      and gastrin levels, whereas the equivalent dose of TGF alpha only caused a
      significant rise in plasma gastrin levels. We conclude that TGF-alpha, like EGF,
      is trophic to the entire gastrointestinal tract of the rat, however, it is a less
      effective mitogen, and has differential hormonal effects.

PMID- 8886582
TI  - Bacterial peptides enhance inflammatory activity in a rat model of colitis.
AB  - Bacterial products released within the gut lumen may alter the course of
      inflammatory bowel lesions. The effect of intraluminal N-formyl methionyl-leucyl
      phenylalanine on mucosal release of inflammatory mediators was investigated in
      normal and colitis rats (at 1 and 7 days after induction of colitis by
      trinitrobenzenesulfonic acid). Under anesthesia, the distal colon was perfused
      using an isosmotic solution with or without synthetic N-formyl methionyl-leucyl
      phenylalanine (100 nmol/ml). Effluents were assayed for eicosanoid (PGE2, TXB2
      and LTB4) concentration. Myeloperoxidase activity was measured in colonic wall
      homogenates. In normal rats, peptide perfusion did not change mucosal release of
      PGE2, TXB2 and LTB4. Colitic rats showed high baseline release of eicosanoids.
      The peptide did not further increase PGE2 and TXB2 release, but significantly
      stimulated LTB4 both on days 1 and 7 after induction of colitis. Rats with high
      myeloperoxidase activity in the colonic wall showed a marked LTB4 response to the
      peptide. Finally, peptide perfusion increased tissue myeloperoxidase activity in
      colitis at day 7 but not in colitis at day 1 or in normal rats. In conclusion,
      bacterial products may activate inflammation. This mechanism of lumen-wall
      interaction might be involved in the perpetuation of inflammatory lesions of the
      colonic mucosa.

PMID- 8886583
TI  - Modulation of putrescine transport in rat intestinal brush-border membrane
      vesicles by fasting and refeeding.
AB  - Fasting and refeeding dramatically alter small intestinal mucosal growth which is
      greatly dependent on polyamine biosynthesis and transport. The aim of this study
      was therefore to examine the uptake of the diamine putrescine by brush-border
      membrane vesicles from the small intestine of rats fasted for 3 days or refed a
      standard diet after a PERIOD OF FASTING. WHILE THE MICHAELIS-MENTEN CONSTANT KM
      WAS essentially unaltered, the maximum velocity (Vmax) for putrescine uptake was
      1.85-fold higher in fasted animals than in ad libitum-fed controls. Refeeding
      fasted rats for 24 h caused a 31% decrease in the Vmax value that, however,
      remained 1.27-fold higher than in control RATS, WHILE THE KM VALUE WAS STILL
      UNCHANGED. FASTING RATS OR refeeding rats after a period of fasting caused only a
      13 or 17% increase, respectively, in the value of the constant for the
      nonsaturable component (P) of putrescine transport relative to the corresponding
      control condition. Our study also confirms that both the mucosal polyamine
      biosynthesis and intestinal content are altered by fasting. We suggest that an
      increased uptake activity may have a conservative role by preventing a
      substantial loss of tissue polyamines during fasting.

PMID- 8886584
TI  - Corneal endothelial permeability after implantation of angle-fitted anterior
      chamber lenses in myopic phakic eyes. Preliminary results.
AB  - This present study aimed to evaluate the corneal endothelium after implantation
      of angle-fixed anterior chamber lenses in myopic phakic eyes. Twelve eyes (9
      patients) with high myopia (more than-14 diopters) were implanted with ZB5M
      lenses (Domilens, France). The corneal endothelium was studied by
      fluorophotometry (endothelial transfer coefficient: kc.ca), specular microscopy
      and ultrasonic pachimetry. Tests were performed prior to and 3 and 6 months after
      the surgery. The Wilcoxon rank test was used for the statistical analysis of the
      data. There was a significant difference (p < 0.05) between the preoperative
      kc.ca (4.15 +/- 0.72 x 10(-3) min-1) and the kc.ca three months after the
      implantation (4.43 +/- 0.87 x 10(-3) min-1). A statistically significant
      difference (p < 0.01) was also found between the three and six months
      postoperative kc.ca (5.31 +/- 0.81 x 10(-3) min-1). There was a significant
      difference (p < 0.05) between the preoperative central endothelial cell density
      (2533 +/- 219 cells/mm2). No significant differences were found in relation to
      the central corneal thickness. In conclusion, three months after the implantation
      of ZB5M lenses to correct high myopia in phakic eyes, the corneal endothelial
      function was altered and continued to be so six months after the operation.

PMID- 8886585
TI  - Risk factors for choroidal neovascularization in young patients: a case-control
      study.
AB  - A pair-matched, case-control design was used to study exposure to Histoplasma
      capsulatum and other environmental factors, and to determine various host
      characteristics including human leukocyte antigen (HLA) typings in 94 young
      patients with macular choroidal neovascularization (CNV) and in 94 controls with
      other eye diseases. Patients with two types of retinal patterns were studied:
      Type I, or those with CNV with one or no chorioretinal atrophic spots in the
      posterior pole or periphery (n = 51), and Type II, or those with CNV and 2 or
      more chorioretinal atrophic spots (n = 43). Our purpose was to explore whether
      these two variants of idiopathic CNV have different and distinguishable
      epidemiologies which may or may not be related to prior exposure to Histoplasma.
      We found that histoplasmin skin tests were negative in all but two Type I cases.
      The combination of the HLA-B7 and HLA-DR2 markers (but not either marker alone)
      was significantly increased in Type I cases. Among Type II cases, HLA-B7, HLA
      DR2, HLA-DQ1, a positive histoplasmin skin test, myopic refractive error, prior
      residence in a histoplasmosis endemic area, occupations involving exposure to
      animals, and hypertension were all significantly increased. Histoplasmin skin
      test responses were positive in 18 Type II cases (45%). In the multivariate
      analysis, only DR2 and the combined presence of DQ1 and a positive histoplasmin
      skin test remained predictive of Type II disease. Our findings suggest that
      histoplasmin sensitivity is associated with some, but not all, cases of Type II
      disease. However, histoplasmin sensitivity appears to have no relationship to
      Type I disease. HLA factors may play a role in both disease types, possibly by
      producing a modified immune response to Histoplasma and/or other unidentified
      agents.

PMID- 8886586
TI  - Topographical reproducibility of small scotoma using computerised dynamic
      fixation target.
AB  - The computer assisted dynamic fixation technique uses the patient's eye movements
      to locate the test stimulus in the central visual field in relation to a randomly
      meandering fixation target. The patient looks at the moving fixation target on a
      high resolution monitor and tries to keep it inside a circle using a joystick.
      The stimuli are presented at predetermined locations in a seemingly random manner
      and the awareness of the stimuli is registered by the patient pressing the
      joystick button. That novel fixation maintenance technique has been combined with
      suprathreshold static light offset (dark-on-bright-light decrement) stimuli
      created on a cathode ray tube and used in mapping of the physiological blind spot
      in 10 healthy eyes. Each eye was examined twice with the same test program in
      order to document the repeatability of the results. On two consective tests, the
      physiological blind spot measured an average of 5.7 degrees horizontally and 6.4
      degrees vertically, using 15% (17 dB) contrast, 16 mm2, single intensity offset
      stimuli. The moving eye method and the light offset stimuli, on repeated testing,
      yielded an average topographical reproducibility rate of 73% in mapping of the
      scotomas, with an average of 1.4 degrees and 0.6 degree variability in the
      vertical and horizontal dimensions of the blind spot respectively.

PMID- 8886587
TI  - Ultrastructure of the anterior lens capsule after vitrectomy with silicone oil
      injection. Correlation of clinical and morphological features.
AB  - To clarify the mechanical difficulties experienced when performing anterior
      capsulorhexis in vitrectomized eyes filled with silicone oil. Five anterior lens
      capsules removed from eyes with a silicone oil history were submitted to light
      and electron microscopic analysis and then compared to two capsules from eyes
      with trauma history and seven capsules from eyes without silicone oil or trauma
      history. Comparable abnormalities of the inner and outer surface of the anterior
      lens capsule were consistently observed after silicone oil fill of the vitreous
      cavity or after traumatic impact to the lens: patches of multilayer epithelial
      cells with interspersed capsule material and connective tissue were observed on
      the posterior surface of the anterior lens capsule. The development of this
      anterior subcapsular tissue plaque is obviously influenced not only by the PVR
      process or by side effects of the surgical procedure but also by the silicone oil
      tamponade or a trauma history. The plaque can be considered primarily responsible
      for the increased mechanical resistance of the lens capsule in all eyes with
      silicone oil / trauma history examined in this study.

PMID- 8886588
TI  - Production of superoxide anion by polymorphonuclear leukocytes from diabetic
      patients with or without diabetic retinopathy.
AB  - Oxygen free radicals have been implicated in the pathogenesis of diabetic
      microangiopathy. The production of superoxide anion (O2-.) by polymorphonuclear
      leukocytes (PMNs) from 45 insulin-dependent diabetes mellitus patients in the
      resting state and in response to a soluble stimulus (phorbol myristate acetate)
      was measured spectrophotometrically and compared with that of 15 age and sex
      matched controls. The resting superoxide anion production by PMNs from diabetic
      patients was significantly higher than that of controls (2.17 +/- 1.32 and 1.35
      +/- 0.6 nmol/10(5) cells/60 min respectively; p = 0.037). In contrast, PMNs from
      diabetic patients released significantly lower levels of superoxide anion
      compared to controls in response to phorbol myristate acetate stimulation (2.33
      +/- 2.04 and 3.55 +/- 0.98 nmol/10(5) cells/60 min respectively; p = 0.044). The
      stimulated superoxide anion production was significantly higher in diabetic
      patients with retinopathy compared to diabetic patients without retinopathy (2.7
      +/- 2.08 and 1.3 +/- 1.6 nmol/10(5) cells/60 min respectively; p = 0.02).
      Furthermore, stimulated PMNs from diabetic patients with proliferative
      retinopathy generated superoxide anion at significantly higher rates than did
      those from diabetics with nonproliferative retinopathy or without retinopathy
      (3.8 +/- 1.5, 2.08 +/- 2.1 and 1.3 +/- 1.6 nmol/10(5) cells/60 min respectively;
      p = 0.005). These results suggest that reactive oxygen species produced by PMNs
      may play a role in the progression of diabetic retinopathy.

PMID- 8886589
TI  - Uveal effusion syndrome complicated by anterior ischemic optic neuropathy.
AB  - We report on a case of idiopathic uveal effusion syndrome complicated by AION. To
      our knowledge such an association hasn't been previously described. We suggest
      that scleral thickening caused obstruction of vortex veins followed by uveal
      effusion and compression of posterior ciliary arteries within their intrascleral
      tract, leading to AION. Nevertheless is can't be excluded that AION was the
      result of mechanical compression on ciliary vessels of optic disc by choroidal
      detachment.

PMID- 8886590
TI  - Stereoacuity testing in patients with retinal and optic nerve disorders.
AB  - A study comparing the relative sensitivity for detecting abnormal stereoacuity in
      patients with retinal or optic nerve disease on clinically used stereoacuity
      tests is not available. It is also not apparent from the ophthalmic literature if
      optic nerve or retinal diseases are likely to have a greater impact on
      stereoacuity performance. We were also interested in determining a level of
      visual acuity loss that would likely results in an impairment of stereoacuity on
      these clinical tests. Forty-two patients with various retinal and optic nerve
      disorders and eighteen normal subjects were evaluated for stereoacuity using
      three tests: Titmus Stereoacuity Test (TST), Randot Stereoacuity Test (RST), and
      TNO Stereoacuity Test (TNO). The performance on these three stereoacuity tests
      was compared with the normal subjects. Additionally, TST scores from our patients
      were compared to predicted TST scores derived from a previously published
      nomogram. For patients with retinal and optic nerve disease, an abnormal score on
      one clinical test of stereoacuity was likely to predict an abnormality on the
      other tests. Performance on the TST relative to the predicted value derived from
      a nomogram was not significantly different for patients with retinal vs. optic
      nerve disease. With some exceptions, patients with visual acuities of 20/30 or
      worse in at least one eye were likely to show abnormal stereoacuity.

PMID- 8886591
TI  - Prognostic importance of retinopathy in acute leukemia.
AB  - This prospective study evaluates the relationship, between the fundus findings in
      leukemic retinopathy and the survival in patients with newly diagnosed acute
      leukemia. Fifty-four newly diagnosed consecutive patients with acute leukemia
      were included in this study. The patients were examined within few days of
      initial admission and diagnosis. Leukemic retinopathy was detected in 19 (35%)
      patients. The observation period ranged from 434 days to 1220 days (mean +/- SD
      880 +/- 225) for those patients who survived. Despite similar chemotherapy
      compared to those without retinopathy (332.4 +/- 99.6 and 76 vs. 640.7 +/- 106
      and 192 days respectively) although survival did not differ significantly (p =
      0.073). Patients with cotton-wool spots had lower mean and median survival times
      than did those without such lesions (168.8 +/- 70.9 and 27 vs. 609.4 +/- 91.4 and
      289 days respectively) and survival differed significantly (p = 0.04). The
      presence of cotton-wool spots and age > or = 40 years were the major adverse
      prognostic factors for survival in multivariate analysis. Cotton-wool spots had a
      more significant adverse prognostic effect than age > or = 40 years (hazard
      function coefficients: 1.0708 for cotton-wool spots vs 0.0355 for age > or = 40
      years). The relative odds of dying among patients with cotton-wool spots were
      about 8 times higher than that for those without this feature, and about 7 times
      higher in patients aged > or = 40 years than that for patients aged < 20 years.
      Our findings suggest that the presence of leukemic retinopathy in general, and
      cotton-wool spots, in particular is a poor prognostic sign for survival in acute
      leukemia.

PMID- 8886592
TI  - Exogenous prostaglandin F2 alpha stimulates utero-ovarian release of
      prostaglandin F2 alpha in sheep: a possible component of the luteolytic mechanism
      of action of exogenous prostaglandin F2 alpha.
AB  - Exogenous prostaglandin F2 alpha (PGF2 alpha) is luteolytic in sheep, but its
      mechanism of action is not completely understood. We hypothesized that exogenous
      PGF2 alpha stimulates the uterine and(or) ovarian secretion of PGF2 alpha and
      that, when intramuscular doses of PGF2 alpha are minimal, the utero-ovarian unit
      is a component of the luteolytic mechanism of action of exogenous PGF2 alpha.
      Thus, this study was conducted to determine whether exogenous PGF2 alpha
      stimulates the utero-ovarian release of PGF2 alpha. Catheters were positioned in
      the vena cava at points cranial and caudal to the entry of utero-ovarian blood,
      and ewes were either hysterectomized and ovariectomized (H/OX) or left intact
      (Intact). Treatments were in a 2 x 2 factorial arrangement (i.e., H/OX and PGF2
      alpha were the main effects), and there were five ewes per treatment group. In
      Experiment 1, on Day 9 after the onset of estrus, either saline or PGF2 alpha (15
      mg) was injected intramuscularly in the neck, and vena caval blood samples were
      collected frequently for 120 min, then less frequently for 48 hr. In Experiment
      2, on Day 9 after estrus or H/OX, either saline of PGF2 alpha (5 mg, then 5 mg 3
      hr later) was injected intramuscularly in the neck, and vena caval blood samples
      were collected frequently for 150 min after each injection. In both experiments,
      exogenous PGF2 alpha induced immediate and significant increases in the utero
      ovarian release of PGF2 alpha. The increases in PGF2 alpha concentrations were
      considerably more pronounced in vena caval blood samples collected cranial than
      in those collected caudal to the entry of utero-ovarian blood, and the increase
      was significantly greater in Intact than in H/OX ewes treated with PGF2 alpha.
      Vena caval concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) increased
      after exogenous PGF2 alpha, but the changes in PGFM were not suitable
      representations of the changes in vena caval concentrations of PGF2 alpha.
      Changes in progesterone concentrations indicated that both PGF2 alpha injection
      regimens were luteolytic. The results from this study indicate that exogenous
      PGF2 alpha stimulates the utero-ovarian production of PGF2 alpha, and we believe
      that the utero-ovarian unit is a component of the luteolytic mechanism of action
      of exogenous PGF2 alpha.

PMID- 8886593
TI  - In vitro model of parathyroid hormone-related protein secretion from mammary
      cells isolated from lactating cows.
AB  - Parathyroid hormone-related protein (PTHrP) is produced by the lactating mammary
      gland and is present in milk in a biologically active form. The goal of this
      investigation was to determine if cells cultured from the lactating mammary
      glands of cows would secrete PTHrP in vitro. Mammary acini were isolated from
      lactating cows at 1-6 wk after calving, and fresh or cryopreserved mammary acini
      were cultured for 14 d on Type I collagen. Cultures on thick layers of collagen
      (2.5 mm) were detached and allowed to contract on Day 6. PTHrP production was
      measured by N-terminal radioimmunoassay and bioassay (increased cAMP levels in
      ROS 17/2.8 osteoblast-like cells). The mammary cells reached confluence at Day 6.
      PTHrP production was low at Day 2 (< 0.5 ng/ml) but increased to peak production
      (2-4 ng/ml) at approximately Day 6 and remained constant until Day 14.
      Immunoreactive and bioactive PTHrP levels in the culture medium correlated well.
      The cultures produced lactoferrin (2,000-2,300 ng/ml and alpha s1-casein (14-19
      ng/ml). Prolactin stimulated PTHrP production approximately 50% on Days 6-14.
      PTHrP production was increased approximately 100% by treatment with epidermal
      growth factor (10 ng/ml) for 2 d. Morphologic evaluation of cultures on thick,
      contracted collagen at Day 14 revealed an inner layer of mammary epithelial cells
      overlying myoepithelial cells and an outer layer of collagen containing stromal
      cells. Immunohistochemistry demonstrated positive staining for PTHrP and
      cytokeratin in both mammary epithelial and myoepithelial cells and alpha-smooth
      muscle actin in myoepithelial cells. These data demonstrated that cryopreserved
      mammary tissue from lactating cows could be cultured in vitro and secreted PTHrP
      in a regulated manner. This in vitro model will be useful to investigate the
      function and regulation of PTHrP in the lactating mammary gland.

PMID- 8886594
TI  - The role of phosphoinositide-derived second messengers in oxytocin-stimulated
      prostaglandin F2 alpha release from endometrium of pigs.
AB  - The mechanism for prostaglandin (PG) F2 alpha release from pig endometrium after
      oxytocin (OT) treatment is unknown. OT may rapidly stimulate inositol (1,4,5)
      trisphosphate (IP3) and diacylglycerol (DAG) formation, consistent with the
      concept of rapid activation of a second-messenger system. In support of this
      hypothesis, endometrial IP3 levels were increased (P < 0.05) within 0.5 min after
      treatment with 0.1 microM OT. In contrast, increased DAG formation was not
      detected after treatment with OT. However, similar to the stimulation of
      endometrial PGF2 alpha secretion observed after OT treatment (P < 0.001), PGF2
      alpha release was increased (P < 0.01) after treatment with phorbol-12-myristate
      13-acetate (PMA), which mimics DAG activation of protein kinase C. Further,
      stimulation of endometrial PGF2 alpha secretion did not result from cell death
      induced by PMA or OT because lactate dehydrogenase, a cytosolic marker of
      cellular integrity, did not leak into the medium after PMA or OT treatment. In
      contrast, 0.5% saponin (positive control for cell death and concomitant release
      of lactate dehydrogenase) increased PGF2 alpha secretion (P < 0.05) and lactate
      dehydrogenase release (P < 0.001). These results indicate that OT induces
      endometrial IP3 production in a rapid manner indicative of a second-messenger
      system. The finding that increased DAG was not also detected after OT treatment
      may reflect rapid metabolism or compartmentalized production of DAG involved in
      the second-messenger stimulation of phospholipase C. The high background of DAG
      used in the biosynthesis of cellular lipids would obscure the rather small
      spatially localized changes in DAG levels resulting from the activation of
      phospholipase C. The finding that DAG was present at approximately 10 to 20-fold
      higher levels than IP3 in resting cells was consistent with this conclusion.

PMID- 8886595
TI  - Expression of alternate growth hormone receptor messenger RNA in ovary and uterus
      of cattle.
AB  - Growth hormone (GH) receptor mRNA is found within the corpus luteum and
      endometrium of cattle. However, binding sites for placental lactogen (PL) but not
      GH are found within these tissues. The objectives were to isolate cDNA for the GH
      receptor within the reproductive tissues of cattle and to examine these cDNA as
      potential variants of the GH receptor that bind PL. Ten cDNA clones were isolated
      from a bovine endometrial cDNA library with a 32P-labeled cDNA of the GH receptor
      extracellular domain. On the basis of restriction enzyme digestion, 2 of the 10
      cDNA clones contained exon 1. The DNA sequence of these clones was determined by
      dideoxy nucleotide sequencing. The exon 1 DNA sequence of each clone (exon 1B)
      was different from the previously reported exon 1 for the bovine GH receptor cDNA
      isolated from liver (exon 1A). Analyses of these cDNA sequences showed that exon
      1B contained significant homology with placental forms of the GH receptor found
      in mouse and human. Unlike the human cDNA, the bovine cDNA isolated from
      endometrium contained an intact third exon. Amplification of GH receptor mRNA by
      reverse transcriptase polymerase chain reaction, with exon 1A- and 1B-specific
      forward primers, showed that exon 1B was expressed in liver, corpus luteum,
      ovary, endometrium, and myometrium. Exon 1A was found almost exclusively in
      liver, and little was found in reproductive tissues. The predicted initiation of
      protein coding for the GH receptor was within the second exon and was not changed
      by the splicing of the alternate first exon. This suggests that the alternate
      mRNA results in the expression of intact GH receptor protein that is similar to
      that found within liver. Alternative promoters (1B) may control the expression of
      the receptor outside the liver. Furthermore, mechanisms other than the
      differential splicing of GH receptor protein may dictate the specificity of PL
      binding within the endometrium and corpus luteum.

PMID- 8886596
TI  - Messenger ribonucleic acid expression for growth hormone receptor, luteinizing
      hormone receptor, and steroidogenic enzymes during the estrous cycle and
      pregnancy in porcine and bovine corpora lutea.
AB  - Growth hormone (GH) and luteinizing hormone (LH) are pituitary hormones involved
      in steroidogenesis in the corpus luteum (CL). The objectives of Experiment I were
      to determine mRNA expression for GH receptor (GHR) and LH receptor (LHR) in
      porcine luteal tissues during the estrous cycle and pregnancy and to relate
      changes in these receptor mRNA with changes in steroidogenic enzyme mRNA for
      cytochrome P450 side-chain cleavage enzyme (P450sec) and 3 beta-hydroxysteroid
      dehydrogenase (3 beta-HSD). Ovaries were collected from gilts during the estrous
      cycle (day 10 [n = 3] and Day 19 [n = 3, regressed CL) and pregnancy (Day 25 [n =
      3] and Day 44 [n = 3]). Tissues were frozen in liquid nitrogen and sectioned.
      Messenger RNA was detected by in situ hybridization, and relative mRNA amounts
      were determined by image analysis. The mRNA for GHR, LHR, P450sec, and 3 beta-HSD
      were detected in the CL on Day 10 of the estrous cycle. None of these mRNA were
      specific to cither large luteal cells (LLC) or small luteal cells (SLC). On Day
      19 of the estrous cycle (regressed CL), mRNA for GHR, P450sec, and 3 beta-HSD
      were decreased (P < 0.01) whereas LHR mRNA disappeared (P < 0.01). During
      pregnancy, mRNA expression increased 2.1-, 1.4-, 1.4-, and 1.2-fold for GHR, LHR,
      P450sec, and 3 beta-HSD, respectively (P < 0.05). The luteal location of GHR mRNA
      in the pig did not agree with that found in our previous studies of GHR mRNA or
      protein in cattle. Therefore, the objective of Experiment 2 was to measure GHR
      mRNA by the use of in situ hybridization in bovine CL during the estrous cycle
      (Day 14; n = 2) and pregnancy (Day 25; n = 2). In situ hybridization demonstrated
      specific expression of GHR mRNA in the LLC of cattle. Furthermore, GHR mRNA
      increased 1.8-fold in CL on Day 25 of pregnancy compared with GHR mRNA on Day 14
      of the estrous cycle (P < 0.01). In adjacent sections, the LHR mRNA was most
      highly expressed in clusters of SLC with 1.6-fold more mRNA on Day 25 of
      pregnancy compared with Day 14 of the estrous cycle (P < 0.01). These results
      suggest that: 1) mRNA for LHR, GHR, P450sec, and 3 beta-HSD are differentially
      regulated during the estrous cycle and pregnancy and 2) the cellular location of
      GHR differs for pigs and cattle, with highly specific expression of GHR in bovine
      LLC but not porcine LLC. This may suggest different functions for GH in the CL of
      these species.

PMID- 8886597
TI  - Stimulative effect of epinephrine on glucose production and utilization rates in
      sheep using a stable isotope.
AB  - The rates of the production and utilization of blood glucose were measured during
      intravenous epinephrine infusion (2.0 nmol kg-1 min-1 for 1 hr) in sheep. An
      isotope dilution method with an infusion of [U-13C]glucose and nonsteady-state
      equations were used for the determination of blood glucose kinetics. Heart rate
      and concentrations of blood glucose, plasma free fatty acids, and lactate
      increased (P < 0.01), whereas plasma insulin concentrations tended to decrease (P
      < 0.06) during epinephrine infusion. The blood glucose turnover rate was 1.9 +/-
      0.1 mg kg-1 min-1 before epinephrine infusion. The rate of blood glucose
      production increased (P < 0.01) to 6.4 +/- 0.5 mg kg-1 min-1 at 20 min after the
      initiation of epinephrine infusion. The blood glucose utilization rate increased
      (P < 0.05) gradually and reached 4.1 +/- 1.2 mg kg-1 min-1 at 60 min after the
      initiation of epinephrine infusion. These results suggest that in sheep,
      epinephrine stimulates the rates of both the production and the utilization of
      blood glucose and that hyperglycemia induced by epinephrine infusion is mainly
      due to a rapid enhancement in the rate of the production of blood glucose.

PMID- 8886598
TI  - Depressed luteinizing hormone response to estradiol in vivo and gonadotropin
      releasing hormone in vitro in experimentally diabetic swine.
AB  - The influence of the acute withdrawal of insulin therapy in streptozocin-diabetic
      female swine was examined for changes in 1) the in vivo pulsatile secretion of
      luteinizing hormone (LH), 2) the preovulatory-like gonadotropin patterns after
      exogenous estradiol, and 3) the in vitro LH secretion by cultured pituitary
      cells. In Experiment 1, ovariectomized diabetic pigs (n = 4) were maintained with
      insulin therapy until 4 d before estradiol benzoate (EB; 7 micrograms/kg body
      weight; subcutaneous) was administered. Four normal ovariectomized pigs, matched
      for age and weight, served as controls. The diabetic state was confirmed by the
      measurement of glucose and insulin concentrations during a glucose tolerance
      test. Pulsatile LH secretion was not influenced by experimental diabetes
      mellitus. However, the expected surge in LH was not induced by EB in diabetic
      gilts. In contrast, three of four normal gilts had a preovulatory-type surge in
      LH. Concentrations of follicle-stimulating hormone in serum were not affected by
      diabetes mellitus. Estradiol concentrations in serum after ER were influenced by
      diabetes mellitus (treatment by time interaction; P < 0.001). In individual
      estradiol profiles, maximum concentrations were similar (104 +/- 10.4 and 91 +/-
      12.0 ng/ml for normal and diabetic pigs, respectively), but the interval to
      maximum concentration was delayed in diabetic pigs (27.5 vs. 9.0 h; SE = 3.0; P <
      0.05). However, the duration of standing estrus (2.2 +/- .3 d) and the interval
      from EB to estrus (3.6 +/- 0.3 d) were not influenced by diabetes mellitus. In
      Experiment 2, LH secretion by cultured cells and residual cellular LH content
      were greater in the pituitaries of normal than diabetic pigs (P < 0.05), and only
      cells from normal pigs responded to gonadotropin-releasing hormone (GnRH), with
      increased production of LH (P < 0.05). In conclusion, diabetes mellitus did not
      affect pulsatile LH secretion but did lower the ability of exogenous estradiol to
      stimulate a surge in vivo and of GnRH to increase LH in vitro, suggesting that
      the pituitary response to estradiol and GnRH is more severely affected by
      diabetes than is the GnRH pulse generator.

PMID- 8886599
TI  - Thyroid-stimulating hormone responses after single administration of thyrotropin
      releasing hormone and combined administration of four hypothalamic releasing
      hormones in beagle dogs.
AB  - Thyrotropin (TSH) responses were determined in eight healthy male beagle dogs
      after a single administration of thyrotropin-releasing hormone (TRH) and the
      combined administration of four hypothalamic releasing hormones, i.e.,
      corticotropin-releasing hormone, growth hormone-releasing hormone, gonadotropin
      releasing hormone, and TRH. In both tests, TRH was administered in a dose of 10
      micrograms/kg. Basal TSH concentrations ranged from 0.07 to 0.27 microgram/l
      (mean +/- SE, 0.14 +/- 0.02 microgram/l). The administration of TRH, alone or in
      the combined test, resulted in a prompt and significant increase in TSH with mean
      (+/-SE) plasma TSH peaks of 1.26 +/- 0.22 micrograms/l at 10 min and 0.85 +/-
      0.17 microgram/l at 30 min, respectively. The area under the curve (0-120 min)
      was significantly lower in the combined test than in the single TRH test, whereas
      the increments were not significantly different. It is concluded that
      measurements of TSH responses to TRH alone and in combination with other
      releasing hormones can be used for the assessment of pituitary thyrotropic cell
      function. In the combined test, the TSH response is slightly lower than that in
      the single test.

PMID- 8886600
TI  - Dietary indole-3-carbinol inhibits FMO activity and the expression of flavin
      containing monooxygenase form 1 in rat liver and intestine.
AB  - Indole-3-carbinol (I3C), a naturally occurring component of cruciferous
      vegetables, has been shown to be an effective cancer chemopreventative agent in a
      number of animal models, and is currently being evaluated in human clinical
      trials. One proposed mechanism of action for I3C involves binding of I3C acid
      condensation products (formed in the stomach) to the Ah receptor, with resultant
      induction of both Phase I and Phase II enzymes. We have previously shown that
      dietary administration of I3C to male Fischer 344 rats markedly induces hepatic
      levels of CYP1A1, and to a lesser degree CYP1A2, CYP2B1/2, and CYP3A1/2. We now
      report that such treatment concurrently inhibits both the activity and expression
      of flavin-containing monooxygenase (FMO) form 1 in rat liver and intestine. This
      inhibition demonstrates both a time and dose dependency, resulting in an 8-fold
      reduction in expression of FMO1 in liver, and almost total ablation of FMO1 in
      intestinal tissues at the highest dietary I3C levels examined. There are many
      examples of xenobiotics that are metabolized by both the CYP and FMO
      monooxygenase systems. In many cases these enzyme systems produce different
      metabolites, which often have strikingly disparate toxicological and/or
      therapeutic properties. Therefore, the marked shift in the ratio of FMO/CYP
      levels in the livers (and other tissues) of rats fed I3C may result in
      significant alterations in the metabolism, disposition, and toxicity of
      xenobiotics. Testing for a similar phenomenon in humans would seem advisable
      before wide-spread administration.

PMID- 8886601
TI  - Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes.
      Role of CYP3A4.
AB  - The microsomal metabolism of fentanyl, a synthetic opioid commonly used in
      anesthesia, was investigated in human liver. Incubation of fentanyl with human
      hepatic microsomes fortified with NADPH resulted in the formation of a single
      major metabolite, namely norfentanyl, as determined by GC/MS. No evidence was
      obtained for the formation of either desproprionylfentanyl or N
      phenylpropionamide, the latter arising via N-dealkylation of the fentanyl amide
      nitrogen. Kinetic analysis of microsomal fentanyl oxidation revealed a single
      K(m) of 117 microM and a Vmax of 3.86 nmol of norfentanyl formed/min/nmol of
      cytochrome P450 (P450). Studies using chemical inhibitors of human P450 enzymes
      revealed that only agents known to inhibit CYP3A4 (e.g. ketoconazole and
      erythromycin) were capable of strongly inhibiting (> or = 90%) microsomal
      fentanyl oxidation. Marked inhibition (> 90%) of norfentanyl formation by liver
      microsomes was also observed with polyclonal antibodies to CYP3A4, whereas
      antibodies to other human P450s were without effect. Furthermore, rates of
      norfentanyl production by 10 individual human liver samples were highly
      correlated (r2 = 0.876, F = 56.46 p < 0.001) with immunochemically determined
      levels of CYP3A4 present in the samples but not with levels of CYP2C8, CYP2C9,
      CYP2C19, or CYP2E1. Our results indicate that CYP3A4 is the major catalyst
      involved in fentanyl oxidation to norfentanyl in human liver. Alterations in
      CYP3A4 levels or activity, as well as the concomitant administration of other
      therapeutic agents metabolized by this P450 enzyme, could lead to marked
      perturbations in fentanyl disposition and, hence, analgesic response.

PMID- 8886602
TI  - Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat,
      human, and cdna-expressed human cytochrome P450.
AB  - Midazolam (MDZ) is metabolized in human liver microsomes by the cytochrome P450
      (CYP) 3A subfamily to 1'-hydroxy (1'-OH) and 4-hydroxy (4-OH) metabolites. MDZ is
      metabolized in the rat primarily to 4-OH MDZ, 1'-OH MDZ, and 1',4-dihydroxy (1',4
      diOH) MDZ. The kinetics of 4-OH and 1'-OH metabolite formation were determined
      using hepatic microsomes from control, Ro 23-7637 and dexamethasone-treated male
      rats. KM values for the major metabolite, 4-OH MDZ, were 24.5, 43.1, and 32.8
      microM, and the corresponding Vmax values were 5.9, 28.9, and 13 nmol/mg/min for
      the control, DEX, and Ro 23-7637-treated animals, respectively KM values for 1'
      hydroxylation of MDZ (the major metabolite) after incubation with human liver
      microsomes from three individuals were 5.57, 2.50, and 3.56 microM, and the
      corresponding Vmax values were 4.38, 0.49, and 0.19 nmol/mg/min, respectively. In
      parallel studies using cDNA-expressed human CYP3A4 microsomes, the KM for 1'-OH
      formation was 1.56 microM, and the corresponding Vmax was 0.16 nmol/mg/min. MDZ
      was not metabolized by cDNA-expressed human CYP2D6, CYP2E1, or CYP1A2, thus
      confirming that these isoforms were not responsible for its biotransformation.
      The formation of 1',4-diOH metabolite in rat and 1'-OH formation in cDNA
      expressed human CYP3A4 microsomes showed a decrease in velocity at high substrate
      concentrations. Inhibition studies showed that MDZ hydroxylation was strongly
      inhibited by ketoconazole and Ro 23-7637 in rat, human, and cDNA-expressed human
      CYP3A4 microsomes. alpha-Naphthoflavone stimulated 1'-OH metabolite formation in
      human and cDNA-expressed human CYP3A4 microsomes at low concentration (10
      microM). Naringenin, a flavonoid present in grapefruit juice, also inhibited MDZ
      metabolism in human liver microsomes. Immunoinhibition studies revealed that
      polyclonal anti-rat CYP3A2 antibody inhibited MDZ metabolism 80-90% in rat,
      human, and cDNA-expressed human CYP3A4 microsomes, thus suggesting that members
      of the CYP3A4 subfamily were involved in the metabolism.

PMID- 8886603
TI  - Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin.
AB  - In vitro methods were used to identify the cytochrome P450 (CYP) enzyme(s)
      involved in S-mephenytoin N-demethylation. S-Mephenytoin (200 microM) was
      incubated with human liver microsomes, and nirvanol formation was quantitated by
      reversed-phase HPLC. S-Mephenytoin N-demethylase activity in a panel of human
      liver microsomes ranged 35-fold from 9 to 319 pmol/min/mg protein and correlated
      strongly with microsomal CYP2B6 activity (r = 0.91). Additional correlations were
      found with microsomal CYP2A6 and CYP3A4 activity (r = 0.88 and 0.74,
      respectively). Microsomes prepared from human beta-lymphoblastoid cells
      transformed with individual P450 cDNAs were assayed for S-mephenytoin N
      demethylase activity. Of 11 P450 isoforms (P450s 1A1, 1A2, 2A6, 2B6, 2E1, 2D6,
      2C8, 2C9, 2C19, 3A4, and 3A5) tested, only CYP2B6 catalyzed the N-demethylation
      of S-mephenytoin with an apparent K(m) of 564 microM. Experiments with P450 form
      selective chemical inhibitors, competitive substrates, and anti-P450 antibodies
      were also performed. Troleandomycin, a mechanism-based CYP3A selective inhibitor,
      and coumarin, a substrate for CYP2A6 and therefore a potential competitive
      inhibitor, failed to inhibit human liver microsomal S-mephenytoin N
      demethylation. In contrast, orphenadrine, an inhibitor of CYP2B forms, produced a
      51 +/- 4% decrease in S-mephenytoin N-demethylase activity in human liver
      microsomes and a 45% decrease in recombinant microsomes expressing CYP2B6. Also,
      both CYP2B6-marker 7-ethoxytrifluoromethylcoumarin O-deethylase and S-mephenytoin
      N-demethylase activities were inhibited by approximately 65% by 5 mg anti-CYP2B1
      IgG/mg microsomal protein. Finally, polyclonal antibody inhibitory to CYP3A1
      failed to inhibit S-mephenytoin N-demethylase activity. Taken together, these
      studies indicate that the N-demethylation of S-mephenytoin by human liver
      microsomes is catalyzed primarily by CYP2B6.

PMID- 8886604
TI  - Ropivacaine, a new amide-type local anesthetic agent, is metabolized by
      cytochromes P450 1A and 3A in human liver microsomes.
AB  - Ropivacaine is a new amide-type local anesthetic agent. Unlike bupivacaine and
      mepivacaine, two structurally similar local anesthetic compounds, ropivacaine is
      exclusively the S-(-)-enantiomer. Ropivacaine is predominantly eliminated by
      extensive metabolism in the liver, with only 1% of the dose being excreted
      unchanged in the urine of humans. Four of the metabolites formed in human liver
      microsomes were identified as 3-OH-ropivacaine, 4-OH-ropivacaine, 2-OH-methyl
      ropivacaine, and 2',6'-pipecoloxylidide (PPX). The enzymes involved in the human
      metabolism of ropivacaine have not been identified. To ascertain which forms of
      cytochrome P450 are involved, ropivacaine was incubated with human microsomes
      from 10 different livers having different cytochrome P450 activities. A strong
      correlation was found between the formation of 3-OH-ropivacaine and CYP1A (r =
      0.87-0.89) and between the formation of 4-OH-ropivacaine, 2-OH-ropivacaine, and
      PPX and CYP3A (r = 0.97-1). Incubation of ropivacaine and human liver microsomes
      in the presence of alpha-naphthoflavone or furafylline, inhibitors of CYP1A,
      decreased the formation of 3-OH-ropivacaine by about 85%, without affecting the
      formation of the other metabolites. The formation of 4-OH-ropivacaine, 2-OH
      methyl-ropivacaine, and PPX was markedly inhibited in the presence of
      troleandomycin, an inhibitor of CYP3A. Microsomes from cells expressing CYP1A2
      formed 3-OH-ropivacaine, whereas 4-OH-ropivacaine, 2-OH-methyl-ropivacaine, and
      PPX were formed in microsomes from cells expressing CYP3A4. Inhibitors of CYP2C
      (sulfaphenazole), CYP2D6 (quinidine), and 2E1 (diethyldithiocarbamate) did not
      inhibit the formation of any metabolite from ropivacaine. In conclusion, CYP1A
      catalyzes the formation of 3-OH-ropivacaine, the main metabolite formed in vivo,
      whereas the formation of 4-OH-ropivacaine, 2-OH-methyl-ropivacaine, and PPX was
      catalyzed by CYP3A.

PMID- 8886605
TI  - Metabolism and excretion of ropivacaine in humans.
AB  - The pharmacokinetics, biotransformation, and urinary excretion of ropivacaine
      (Naropin), a new local anesthetic agent, have been studied in six healthy male
      volunteers after a 15-min iv infusion of 152 mumol (50 mg) of [14C]ropivacaine,
      with a specific radioactivity of 22.5 kBq/mumol (8.8 kBq/mg). Blood, urine, and
      feces were collected for up to 96 hr after administration. The plasma and urine
      samples were analyzed for unchanged ropivacaine and for four of its metabolites,
      i.e. 3-OH-2',6'-pipecoloxylidide (3-OH-PPX), 4-OH-ropivacaine, 3-OH-ropivacaine,
      and the N-dealkylated metabolite PPX, using GC and HPLC methods. The presence of
      2,6-xylidine in plasma was also analyzed. The metabolites were quantified after
      acidic hydrolysis. The radioactivity could be followed in plasma for up to 14 hr
      after administration, with ropivacaine being the predominant compound in the
      early samples. The concentrations of the aforementioned metabolites in plasma
      were below or just above the lower limit of quantification, and no 2,6-xylidine
      was detected. The maximum plasma concentration of ropivacaine was 5.9 +/- 2.6
      microM (1.6 +/- 0.7 mg/liter), with an elimination half-life of 2.0 +/- 0.3 hr
      and a total plasma clearance of 397 +/- 127 ml/min. The maximum plasma
      concentration value for the total radioactivity was 5.5 +/- 2.4 microM (1.5 +/-
      0.7 mg/liter) and the elimination half-life was 5.4 +/- 2.9 hr. [14C]Ropivacaine
      and its metabolites were mainly excreted in the urine, with a total recovery of
      86 +/- 3% in the urine and 9 +/- 1% in the feces after 96 hr. Most of the
      radioactivity (about 68%) was excreted within 12 hr. Ropivacaine was extensively
      metabolized, and only 1 +/- 0.6% of the dose was excreted unchanged in the urine.
      The major metabolite identified in the urine was conjugated 3-OH-ropivacaine,
      which was excreted to an extent of 37 +/- 3% of the dose. The urinary excretion
      of 4-OH-ropivacaine was < 1%, whereas the N-dealkylated metabolites PPX and 3-OH
      PPX accounted for 2 and 3% of the dose, respectively. An additional hydroxylated
      metabolite, 2-OH-methyl-ropivacaine, was tentatively identified in the urine of
      some volunteers, accounting for about 4-15% of the dose.

PMID- 8886606
TI  - Comparative metabolism of the nonsteroidal antiinflammatory drug, aceclofenac, in
      the rat, monkey, and human.
AB  - Aceclofenac ([2-(2',6'-dichlorophenylamino)phenyl]acetoxyacetic acid) is a novel
      nonsteroidal antiinflammatory drug, the pharmacokinetics and drug metabolism of
      which show species differences. After oral administration to the rat, circulating
      aceclofenac rapidly disappears yielding [2-(2',6'
      dichlorophenylamino)phenyl]acetic acid (diclofenac), which is then further
      oxidized to [2-(2',6'-dichloro-4'-hydroxyphenylamino)phenyl[acetic acid (4'
      hydroxydiclofenac) and [2-(2',6'-dichloro-4'-hydroxyphenylamino)phenyl]acetic
      acid (4'-hydroxydiclofenac) and [2-(2',6'-dichlorophenylamino)-5
      hydroxyphenyl]acetic acid (5-hydroxydiclofenac). This is a minor route in humans,
      wherein aceclofenac is hydroxylated to [2-(2',6'-dichloro-4'
      hydroxyphenylamino)phenyl]acetoxyacetic acid (4'-hydroxyaceclofenac), which
      becomes the major metabolite. In the monkey, the conversion of aceclofenac to
      diclofenac takes place, but to a much lesser extent than in the rat, and the 4'
      hydroxylated metabolites from both compounds are found in monkeys' urine. The
      mechanistic basis for this species-dependent variations seems to be the different
      stability of the drug toward liver esterases. In the rat, the most efficient
      aceclofenac-hydrolyzing activity is found in hepatic microsomes (Vmax = 2113 +/-
      177 pmol/min/mg protein and KM = 191 +/- 40 microM) and cytosol (Vmax = 479 +/-
      37 pmol/min/mg protein and KM = 75 +/- 22 microM). Consequently, incubation of
      aceclofenac with cultured rat hepatocytes or in the rat in vivo results in a
      rapid hydrolysis of the drug, followed by oxidative metabolism of the resulting
      diclofenac, yielding 4'- and 5-hydroxylated derivatives as the major metabolites.
      In contrast, the aceclofenac ester bond is much more stable toward human hepatic
      microsomal (Vmax = 27 +/- 10 pmol/min/mg protein and KM = 792 +/- 498 microM) and
      cytosolic (Vmax = 87 +/- 5 pmol/min/mg protein and KM 218 +/- 30 microM)
      esterases, and 4'-hydroxyaceclofenac becomes the major metabolite in cultured
      human hepatocytes, as well as in human urine. The research presented herein also
      illustrates the suitability of cultured human hepatocytes for predicting
      aceclofenac metabolism in humans.

PMID- 8886607
TI  - Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6
      and 3A4.
AB  - The anesthetic halothane undergoes extensive oxidative and reductive
      biotransformation, resulting in metabolites that cause hepatotoxicity. Halothane
      is reduced anaerobically by cytochrome P450 (P450) to the volatile metabolites 2
      chloro-1,1-difluoroethene (CDE) and 2-chloro-1,1,1-trifluoroethane (CTE). The
      purpose of this investigation was to identify the human P450 isoform(s)
      responsible for reductive halothane metabolism. CDE and CTE formation from
      halothane metabolism by human liver microsomes was determined by GC/MS analysis.
      Halothane metabolism to CDE and CTE under reductive conditions was completely
      inhibited by carbon monoxide, which implicates exclusively P450 in this reaction.
      Eadie-Hofstee plots of both CDE and CTE formation were nonlinear, suggesting
      multiple P450 isoform involvement. Microsomal CDE and CTE formation were each
      inhibited 40-50% by P450 2A6-selective inhibitors (coumarin and 8
      methoxypsoralen) and 55-60% by P450 3A4-selective inhibitors (ketoconazole and
      troleandomycin). P450 1A-, 2B6-, 2C9/10-, and 2D6-selective inhibitors (7,8
      benzoflavone, furafylline, orphenadrine, sulfaphenazole, and quinidine) had no
      significant effect on reductive halothane metabolism. Measurement of product
      formation catalyzed by a panel of cDNA-expressed P450 isoforms revealed that
      maximal rates of CDE formation occurred with P450 2A6, followed by P450 3A4. P450
      3A4 was the most effective catalyst of CTE formation. Among a panel of 11
      different human livers, there were significant linear correlations between the
      rate of CDE formation and both 2A6 activity (r = 0.64, p < 0.04) and 3A4 activity
      (r = 0.64, p < 0.03). Similarly, there were significant linear correlations
      between CTE formation and both 2A6 activity (r = 0.55, p < 0.08) and 3A4 activity
      (r = 0.77, p < 0.005). The P450 2E1 inhibitors 4-methylpyrazole and
      diethyldithiocarbamate inhibited CDE and CTE formation by 20-45% and 40-50%,
      respectively; however, cDNA-expressed P450 2E1 did not catalyze significant
      amounts of CDE or CTE production, and microsomal metabolite formation was not
      correlated with P450 2E1 activity. This investigation demonstrated that human
      liver microsomal reductive halothane metabolism is catalyzed predominantly by
      P450 2A6 and 3A4. This isoform selectivity for anaerobic halothane metabolism
      contrasts with that for oxidative human halothane metabolism, which is catalyzed
      predominantly by P450 2E1.

PMID- 8886608
TI  - Disposition of gemfibrozil and gemfibrozil acyl glucuronide in the rat isolated
      perfused liver.
AB  - Acyl glucuronides are reactive electrophilic metabolites and in vivo are readily
      hydrolyzed, undergo intramolecular rearrangement, and bind covalently to
      proteins. The isolated perfused liver preparation, using male Sprague-Dawley
      rats, was used to examine the hepatic disposition of the fibrate hypolipidemic
      agent gemfibrozil and its acyl glucuronide metabolite, 1-O-gemfibrozil-beta-D
      glucuronide. Using a recirculating design, erythrocyte-free perfusion medium
      containing 1% (w/v) albumin was delivered to the liver via the portal vein at a
      flow rate of 30 ml/min, and for each experiment was spiked with either
      gemfibrozil (N = 4) or 1-O-gemfibrozil-beta-D-glucuronide (N = 4) at initial
      concentrations of 120 microM and 21 microM, respectively. In the gemfibrozil
      perfusions, the mean (SD) total perfusate clearance, half-life, hepatic
      extraction ratio of gemfibrozil, and the fraction of eliminated gemfibrozil
      excreted in bile as the glucuronide conjugate were 2.73 (0.30) ml/min, 76.9 (5.6)
      min, 0.091 (0.012), and 0.347 (0.154), respectively. In the 1-O-gemfibrozil-beta
      D-glucuronide perfusions, the mean (SD) total perfusate clearance, half-life,
      hepatic extraction ratio, and fraction excreted in bile as the glucuronide
      conjugate were 19.5 (2.1) ml/min, 8.7 (0.9) min, 0.649 (0.068), and 0.534
      (0.077), respectively. The higher hepatic extraction ratio for 1-O-gemfibrozil
      beta-D-glucuronide could mostly be attributed to its higher unbound fraction in
      perfusate (0.182), compared with that of the parent drug (0.004), because the
      conjugate had a lower intrinsic clearance (305 ml/min) compared with the aglycone
      (751 ml/min). Control perfusions, conducted in the absence of a liver, showed
      negligible degradation of 1-O-gemfibrozil-beta-D-glucuronide over 90 min.
      However, in the presence of a liver, approximately 25% of 1-O-gemfibrozil-beta-D
      glucuronide added to perfusate was hydrolyzed to gemfibrozil over 90 min. The
      study demonstrates the importance of the liver in the formation, uptake,
      hydrolysis, and excretion of 1-O-gemfibrozil-beta-D-glucuronide.

PMID- 8886609
TI  - Xenobiotic metabolism in rat, dog, and human precision-cut liver slices, freshly
      isolated hepatocytes, and vitrified precision-cut liver slices.
AB  - Human, rat, and dog phase I and phase II xenobiotic metabolism in precision-cut
      liver slices and freshly isolated hepatocytes was compared using a range of
      substrates. Carbamazepine (50 microM) and styrene (2 mM) were used as probes to
      study the maintenance of cytochrome P450 and epoxide hydrolase-mediated
      metabolism in male Sprague-Dawley rat, precision-cut liver slices and
      hepatocytes. Carbamazepine metabolism in both models resulted in the formation of
      the bioactive 10,11-epoxide (KM = 766 microM and Vmax = 2.5 pmol/min/mg protein
      in precision-cut slices). Epoxide formation was higher (2.4-fold) in hepatocytes
      than slices. Styrene was deactivated to styrene diol at a higher rate in
      hepatocytes (9.7-fold) than slices. The lower rate of metabolism in slices
      compared with hepatocytes confirms our previous observations using testosterone,
      7-ethoxycoumarin, 1-chloro-2,4-dinitrobenzene and 2-(5'-chloro-2'
      phosphoryloxyphenyl)-6-chloro-4-(3H)-quinazolinone in the rat. Testosterone 6
      beta-hydroxylation in human liver slices was similar to cultured hepatocytes, but
      lower than in freshly isolated hepatocytes. 7-Ethoxycoumarin O-deethylation was
      higher in freshly isolated human hepatocytes, as was the ratio of glucuronide to
      7-hydroxycoumarin. Testosterone hydroxylations, 7-ethoxycoumarin O-deethylation,
      and 1-chloro-2,4-dinitrobenzene conjugation were also lower in male beagle dog
      slices, compared with freshly isolated hepatocytes. Attempts at long-term
      preservation of dog liver slices using vitrification and storage for up to 9 days
      at -196 degrees C resulted in the retention of phase I and phase II metabolism,
      although conjugation was lower than in freshly prepared slices. Xenobiotic
      metabolism in short-term incubations is consistently lower in dog and rat
      precision-cut slices than in freshly isolated hepatocytes; whereas, in humans,
      this quantitative difference is partly hidden by the large interindividual
      variation.

PMID- 8886610
TI  - Kinetics and selectivity of mechanism-based inhibition of guinea pig hepatic and
      pulmonary cytochrome P450 by N-benzyl-1-aminobenzotriazole and N-alpha
      methylbenzyl-1-aminobenzotriazole.
AB  - The time dependence for mechanism-based inactivation of cytochrome P450 (P450)
      dependent 7-pentoxyresorufin O-depentylation (PROD), 7-ethoxyresorufin O
      deethylation (EROD), and 7-methoxyresorufin O-demethylation (MROD) activities by
      N-benzyl-1-aminobenzotriazole (BBT) and N-alpha-methylbenzyl-1-aminobenzotriazole
      (alpha MB) was investigated in hepatic and pulmonary microsomes from
      phenobarbital-treated guinea pigs. In the presence of NADPH, both compounds
      inhibited P450-dependent catalytic activity in a time- and concentration
      dependent manner. Inactivation of hepatic PROD activity was more rapid (t1/2 =
      13.2 vs. 155 min) for 0.1 microM alpha MB when compared with equimolar BBT. On
      the other hand, hepatic EROD inactivation was more rapid (t1/2 = 8.1 vs. 11 min)
      with 0.1 microM BBT, compared with equimolar alpha MB. Inactivation of pulmonary
      PROD activity was the most rapid and potent, with an apparent half-life for
      inactivation of t1/2 = 0.94 and 32.2 min for 0.025 microM alpha MB and BBT,
      respectively. Incubation of hepatic microsomes for 45 min in the presence of
      NADPH and 10 microM BBT or alpha MB resulted in > 90% inhibition of PROD, EROD,
      and MROD activities. After washing by repeated sedimentation and resuspension,
      inhibition of PROD (78%; 93% for BBT and alpha MB, respectively), EROD (80% and
      50%), and MROD (15% and 3%) activities was reversed to varying degrees. We
      conclude that BBT and alpha MB are rapidly metabolized to products that inhibit
      individual P450 isozymes by both mechanism-based (P4502B and P4501A1) and
      reversible (P4501A2) mechanisms. Of the two inhibitors, alpha MB is relatively
      more potent and selective for guinea pig lung P4502B isozyme(s).

PMID- 8886611
TI  - Stereoselective metabolism of a new anticonvulsant drug candidate, losigamone, by
      human liver microsomes.
AB  - Losigamone (LSG) is a new candidate anticonvulsant drug under going preclinical
      and clinical development. Metabolism of racemic (+/-)-LSG and its two
      enantiomers, AO-242 [(+)-LSG] and AO-294 [(-)-LSG], was studied using human liver
      microsomes and recombinant cytochrome P450 isozymes. HPLC with both UV and
      electrochemical detection was used for analysis of the incubation media. Five
      metabolites (M1, M2, M3, M4, and M5) were generated from racemic (+/-)-LSG by
      both human liver microsomes and recombinant enzymes. Stereoselective metabolism
      was observed when each enantiomer was incubated separately with human liver
      microsomes. M1 was the major metabolite produced from (+)-LSG, whereas M3, M4,
      and M5 were primarily produced from (-)-LSG. The production of M1 from (+)-LSG
      was markedly inhibited by (-)-LSG, indicating a metabolic enantiomer/enantiomer
      interaction. (+/-)-LSG enantiomers were selectively metabolized by recombinant
      cytochrome P450 2A6, and the metabolism of (+)-LSG and (-)-LSG by human liver
      microsomes was preferentially inhibited by coumarin, a cytochrome P450 2A6
      selective compound.

PMID- 8886612
TI  - Absorption and disposition kinetics of 3,3',4,4'-tetrachloroazoxybenzene in the
      male Fischer 344 rat.
AB  - 3,3',4,4'-Tetrachloroazoxybenzene (TCAOB) is a structural analog of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). It is formed as a byproduct during the
      synthesis of industrial products such as herbicides. TCAOB is a ligand for the Ah
      receptor and, at much higher doses, exhibits toxicities similar to TCDD. Although
      the reduced in vivo toxicity of TCAOB probably reflects differences in
      disposition, this study characterized its absorption and disposition kinetics.
      Male Fischer 344 rats were administered [14C]TCAOB (3.4 or 34 mg/kg p.o., 3.4
      mg/kg i.v.), and the excretion of the radiolabel was monitored over 96 hr. After
      the low and high dose, 35% and 30% of the [14C]TCAOB were eliminated in the
      urine, with 55% and 54% eliminated in the feces. At 96 hr, the adipose
      tissue:blood ratios of [14C]TCAOB equivalents were 8 and 26 for the low and high
      doses, respectively. After the intravenous dose of TCAOB, the adipose
      tissue:blood ratio was 21 at 96 hr. Other tissue:blood ratios were of little
      significance (0.06-3.2). Pharmacokinetic parameters indicate that the parent
      molecule is cleared from blood with an average half-life of 7 hr and an average
      clearance of 11 ml/min.kg. Absolute bioavailability was calculated to be
      approximately 9%. Urine contained a variety of dichlorolaniline conjugates, which
      support the importance of azo reduction in the disposition of TCAOB. When
      compared with TCDD, the absorption of TCAOB is greatly reduced and the
      elimination of metabolites greatly enhanced. Therefore, at equal molar oral
      doses, TCAOB would express lower levels of Ah receptor-mediated toxicity than
      those defined for TCDD.

PMID- 8886613
TI  - Busulfan conjugation by glutathione S-transferases alpha, mu, and pi.
AB  - Busulfan is eliminated by glutathione S-transferase (GST)-catalyzed conjugation
      with glutathione (GSH). We have characterized the busulfan-conjugating activity
      of purified human liver GSTA1-1, GSTA1-2, GSTA2-2, GSTM1-1, and placental GSTP1
      1. Isoforms were purified from cytosol by GSH-affinity chromatography and
      chromatofocusing. In addition, the busulfan-conjugating activity of cDNA
      expressed GTH1 and GTH2, corresponding to GSTA1-1 and GSTA2-2, were
      characterized. The major product of busulfan conjugation, a thiophenium ion
      (THT+), was assayed by GC/MS after conversion to tetrahydrothiophene (THT). THT+
      formation rate increased linearly with busulfan concentration up to its
      solubility limit for all GST isoforms. Because Vmax and KM could not be
      determined separately, the slope of the velocity vs. substrate concentration
      plot, Vmax/KM was used to compare isoform activities. Vmax/KM for GSTA1-1 was
      7.95 microliters/min/mg protein, the highest busulfan-conjugating activity of all
      human liver and placenta isoforms evaluated. GSTM1-1 and GSTP1-1, respectively,
      had 46% and 18% of the activity of GSTA1-1. Since the polymorphic mu-class GST
      catalyzed busulfan conjugation, we examined busulfan clearance in 50 patients
      undergoing high-dose busulfan before bone marrow transplantation. Busulfan
      clearance was normally distributed, suggesting that GSTM1-1 does not contribute
      significantly to the elimination of busulfan from the body. We conclude that
      GSTA1-1 is the major isoform catalyzing busulfan conjugation, whereas GSTM1-1 and
      GSTP1-1 may be important in the protection of specific cells.

PMID- 8886614
TI  - Covalent binding to DNA in vitro of 2',3'-oxides derived from allylbenzene
      analogs.
AB  - Epoxidation at the allylic side chain is a major metabolic pathway for
      allylbenzene and its naturally occurring analogs safrole, estragole, and eugenol.
      We demonstrate herein that the epoxide metabolites of allylbenzene, estragole,
      and safrole can form covalent adducts with DNA in vitro, binding primarily to
      guanine, but also to the other three DNA bases. Epoxide hydrolases can prevent
      the binding of allylbenzene 2',3'-oxide to DNA in vitro. Four distinct adducts
      were detected by analytical TLC after the reaction of 2'-deoxyguanosine with
      allylbenzene 2',3'-oxide. One unstable adduct was formed rapidly, but gradually
      disappeared, whereas the other three adducts were formed more slowly but
      persisted. The major persistent adduct, which was isolated by preparative
      chromatography, was examined by MS and NMR. The structure of this adduct is 3'-N1
      deoxyguanosyl-(2'-hydroxypropylbenzene). In addition, a generally applicable
      paradigm for the identification of deoxyguanosine or guanosine adducts by 13C and
      1H NMR spectroscopy is presented.

PMID- 8886615
TI  - Hemodynamic effects of N-acetylamrinone in a porcine model of group B
      streptococcal sepsis.
AB  - High plasma concentrations of N-acetylamrinone, a primary metabolite of amrinone,
      are measured in some children during prolonged amrinone infusion. The purpose of
      this investigation was to determine if N-acetylamrinone has direct hemodynamic
      effects independent of amrinone. Twenty neonatal piglets received an infusion of
      6 x 10(9) colony-forming units/kg of group B Streptococcus to induce sepsis.
      Subsequently, they were divided into 1 of 3 groups and received a 1-hr infusion
      of either normal saline (N = 4); 8 mg/kg amrinone, followed by 20
      micrograms/kg/min (N = 9); or 8 mg/kg N-acetylamrinone, followed by 20
      micrograms/kg/min (N = 7). Hemodynamic measurements and arterial/venous blood-gas
      determinations were obtained every 30 min during the study. Systemic vascular
      resistance and pulmonary vascular resistance were calculated. One milliliter of
      blood was obtained every 30 min during drug administration to determine plasma
      amrinone and N-acetylamrinone concentrations. The mean amrinone plasma
      concentrations measured at 30 and 60 min during the infusion time in the group
      receiving amrinone were 8.8 +/- 1.1 and 6.9 +/- 0.7 micrograms/ml, respectively.
      These animals experienced a significant decrease in mean pulmonary artery
      pressure and pulmonary vascular resistance, compared with saline controls after a
      30-min infusion of amrinone. The mean N-acetylamrinone plasma concentrations
      measured at 30 and 60 min during the N-acetylamrinone infusion were 7.3 +/- 0.8
      and 5.7 +/- 0.6 micrograms/ml, respectively. There was no difference between any
      hemodynamic parameter measured in these animals, compared with saline controls at
      any time during the infusion. We conclude that amrinone, but not N
      acetylamrinone, causes pulmonary vasodilation in a porcine model of sepsis and
      that the parent drug is the sole active component in amrinone.

PMID- 8886616
TI  - Disposition of metabolically radiolabeled CE9.1--a macaque-human chimeric anti
      human CD4 monoclonal antibody--in transgenic mice bearing human CD4.
AB  - IDEC-CE9.1 is a macaque/human chimeric IgG1 monoclonal antibody (mAb) directed
      against the human T-lymphocyte receptor, CD4. CE9.1 is highly specific for the
      human receptor and is known to cross-react only with chimpanzee CD4. Thus,
      limited in vivo investigations have been performed that would be expected to
      reflect the behavior of this mAb in humans. CE9.1 was metabolically radiolabeled
      using [3H]leucine, and studies of the distribution and pharmacokinetics of
      [3H]CE9.1 were performed in transgenic mice bearing either the hCD4 receptor in
      place of the mouse receptor (CD4+), or no CD4 receptor (CD4-). Single-dose
      studies were performed after intravenous administration of approximately 0.4 and
      100 mg/kg. The disposition of CE9.1 was highly dependent on the presence and
      distribution of the hCD4 receptor. After a low intravenous dose to CD4+ mice,
      rapid loss of [3H]CE9.1 from plasma (mean residence time < 1 hr) was accompanied
      by accumulation of radioactivity in the spleen (a maximum of 18% of the
      administered dose at 2 hr). By contrast, no significant uptake of radiolabel was
      observed in the spleen of CD4- mice after a low intravenous dose (< 1%), and
      plasma radioactivity exceeded 40% of the administered dose at 24 hr. Significant
      accumulation of radiolabel was observed in the liver of both CD4+ and CD4- mice
      (maximum of 9-13%), suggesting this process was not CD4-receptor-mediated. After
      a high intravenous dose to CD4+ mice, the mean residence time of CE9.1 was
      approximately 24 hr, and dose-normalized plasma area under the concentration vs.
      time curve was within a factor of 2 of that observed in CD4- mice. Spleen
      radioactivity was < 1% after a high intravenous dose to CD4+ mice, whereas in the
      liver, the profile of radioactivity was similar in CD4+ mice at 0.4 and 100
      mg/kg.

PMID- 8886618
TI  - Signal transduction of GnRH receptor in the reproductive tract tumor.

PMID- 8886617
TI  - Substrate probe for the mechanism of aromatic hydroxylation catalyzed by
      cytochrome P450.
AB  - The effect of branch pathways on the observed intramolecular isotope effect and
      deuterium retention associated with 6- and 7-hydroxylation of selectively
      monodeuterated (R)- and (S)-warfarin with cytochrome P450 (CYP) 2C9 and CYP1A2
      were studied. cDNA-expressed CYP2C9 was incubated with enantiomerically pure (S)
      7d1- and (S)-6d1-warfarin, and expressed CYP1A2 was incubated with
      enantiomerically pure (R)-7d1- and (R)-6d1-warfarin. A high degree of deuterium
      retention was observed in all metabolites, independent of the stereochemistry of
      the substrate or CYP isoform. No deuterium kinetic isotope effect was observed
      for the formation of 6-hydroxy- or 7-hydroxywarfarin in the case of the (S)-6d1
      warfarin metabolism by CYP2C9, or for the formation of 6-hydroxy-, 7-hydroxy-,
      and 8-hydroxywarfarin in the case of the (R)-6d1-warfarin metabolism by CYP1A2.
      Deuterium isotope effects of 1.17 and 1.23 accompanied formation of 7
      hydroxywarfarin from (S)-7d1-warfarin by CYP2C9 and from (R)-7d1-warfarin by
      CYP1A2, respectively. These observations are consistent with the addition
      rearrangement pathway for aromatic hydroxylation, in which a triplet-like active
      oxygen species initially adds to the pi system, resulting in a tetrahedral
      intermediate. The intermediate subsequently rearranges to generate the phenol,
      the final product of the reaction.

PMID- 8886619
TI  - Clinical implications of renal cyst in primary aldosteronism.
AB  - The present study surveyed 69 patients with aldosteronoma to study the clinical
      implications of renal cysts demonstrated in computed tomography. Patients who had
      cysts (n = 16, 23.2%) were older and had a longer duration of hypertension and
      more severe hypokalemia than those without cysts (n = 53). Patients with cysts
      therefore had longer-term, more severe hypokalemia than those without cysts.
      Endogeneous creatinine clearance (Ccr), measured in 61 patients, was
      significantly lower in patients with cysts (58.4 +/- 7.1 ml/min, n = 16) than in
      those without cysts (77.3 +/- 7.1 ml/min, n = 45, P = 0.0039). This significant
      difference was observed even after adjusting for covariables (age, duration of
      hypertension, and serum potassium) between the two groups by analysis of
      covariance (ANCOVA). No significant difference was observed in gender, blood
      pressure, serum creatinine, plasma aldosterone, or PRA. Age, serum potassium
      levels, and systolic and diastolic blood pressure were the significant
      determinants in predicting Ccr in a backward stepwise multiple regression
      analysis (r = 0.505, n = 61, P = 0.0025). Cysts were graded into four classes on
      the basis of number and size. Cyst grading correlated negatively with Ccr at a
      Spearman rank correlation (rho = -0.33, n = 61, P = 0.0103). The incidence of
      chronic renal failure was significantly higher in patients with cysts (18.8%)
      than in patients without (0%) in a Fischer's exact probability test (P = 0.0107).
      Thus, both renal cysts and dysfunction arose and/or developed from common roots,
      i.e., the duration and severity of hypokalemia, in primary aldosteronism. In
      addition, we surveyed 27 patients with pheochromocytoma. Patients with renal
      cysts (n = 8) had a significantly longer duration of hypertension than those
      without cysts. No significant difference was observed in Ccr between patients
      with and those without cysts. Thus, a significant link between renal cysts and
      Ccr was a specific feature of primary aldosteronism, but not of pheochromocytoma.
      In summary, the renal cysts in primary aldosteronism should be recognized as a
      significant complication representing the extent of renal injury and dysfunction.

PMID- 8886620
TI  - Comparison of immunocytologic localization of insulin-like growth factor binding
      protein-4 in normal and polycystic ovary syndrome human ovaries.
AB  - The cytologic localization and cellular levels of insulin-like growth factor
      binding protein-4 (IGFBP-4) in follicular and stromal compartments of normal and
      polycystic ovary syndrome (PCOS) ovaries during follicular growth and regression
      were investigated by the avidin/biotin immunoperoxidase method with a polyclonal
      antibody to human IGFBP-4, and a comparative assessment of IGFBP-4 expression in
      normal and PCOS ovaries was provided. In normal human ovaries, IGFBP-4 was
      immunolocalized to the oocyte throughout follicular growth, while the surrounding
      granulosa and theca cells were negligible for IGFBP-4 immunostaining in
      primordial, preantral and antral follicles. IGFBP-4 immunostaining became
      apparent, however, in the lutein cells of corpora lutea and the granulosa and
      theca cells of atretic follicles. In PCOS ovaries, prominent immunostaining for
      IGFBP-4 was apparent not only in the oocyte, but also in the surrounding
      granulosa cells in preantral follicles. In antral follicles from PCOS women
      without hyperinsulinemia, IGFBP-4 immunostaining was more prominent in the
      granulosa cells than the theca cells, whereas in antral follicles from PCOS women
      with hyperinsulinemia IGFBP-4 immunostaining was more prominent in the theca
      cells than the granulosa cells. Furthermore, in atretic follicles within PCOS
      ovaries IGFBP-4 immunostaining was prominent in the theca cells, regardless of
      the association of hyperinsulinemia. These results demonstrate for the first time
      that there is a great difference in cellular expression of IGFBP-4 between normal
      and PCOS human ovaries. In light of the high affinity of IGFBP-4 for IGF-1, the
      abundant expression of IGFBP-4 in granulosa and theca cells of preantral and
      antral follicles of PCOS ovaries may lead to decreases in the bioavailability of
      IGF-I in those follicles. The decrease in IGF-I-mediated stimulation of
      gonadotropin actions on granulosa and theca cells in preantral and antral
      follicles may impair the induction of aromatase activity, causing an androgenic
      microenvironment which is characteristic of atretic follicles and PCOS follicles.

PMID- 8886621
TI  - Two cases of malignant pheochromocytoma treated with cyclophosphamide,
      vincristine and dacarbazine in a combined chemotherapy.
AB  - Two patients with malignant pheochromocytoma were treated with a combination
      chemotherapy regimen consisting of cyclophosphamide vincristine, and dacarbazine
      (CVD). With the first few cycles of the treatment, one patient, a 29-year-old man
      had a marked improvement of clinical symptoms and decreases in tumor size and
      catecholamine levels in plasma and urine. He had been in a clinically stable
      condition for 18 months but died 34 months after starting of this treatment
      because the CVD regimen became ineffective and rapid growth of the metastatic
      tumors occurred. The other patient, a 35-year-old man showed no significant
      change in tumor size but decreases in hormonal levels in response to CVD regimen.
      The patient has been in clinically stable condition in a follow-up of 24 months.
      The combined chemotherapy with CVD appears to be effective for advanced malignant
      pheochromocytoma.

PMID- 8886622
TI  - Hyperglycemia decreases dehydroepiandrosterone in Japanese male with impaired
      glucose tolerance and low insulin response.
AB  - Recent studies indicate that experimentally induced hyperinsulinemia may reduce
      serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S).
      Serum DHEA and DHEA-S decrease in diabetic patients, but the mechanism by which
      hyperglycemia decreases DHEA and DHEA-S is unknown. In this study, we
      investigated the effect of hyperglycemia on DHEA and DHEA-S in impaired glucose
      tolerance (IGT) by means of the 75g-oral glucose tolerance test (OGTT). We
      selected 30 male IGT patients receiving diet therapy only, whose insulinogenic
      Index was under 0.3. Oral glucose challenge significantly reduced DHEA (P =
      0.0001) and DHEA-S (P < 0.05) at 60 and 120 min after OGTT. Setting the value of
      DHEA and DHEA-S at time zero as 100%, we calculated the DHEA and DHEA-S values at
      60 and 120 min after OGTT as %DHEA(-S) 60 min and %DHEA(-S) 120 min,
      respectively. DHEA and DHEA-S at time zero showed no correlation with BMI, HbA1c,
      the sum of insulin values (sigma IRI) or the area under the curve of plasma
      glucose (AUC). We found decreases in %DHEA 60 min (r = -0.411, P < 0.05), %DHEA-S
      60 min (r = -0.508, P < 0.01) and %DHEA-S 120 min (r = -0.393, P < 0.05) as AUC
      increased, but sigma IRI showed no correlation with %DHEA(-S) 60 min or %DHEA(
      S)120 min. We conclude that the depression of DHEA and DHEA-S after OGTT is
      attributable to hyperglycemia in male Japanese IGT with low insulin response.

PMID- 8886623
TI  - Characteristics of growth hormone secretion responsiveness to growth hormone
      releasing peptide-2 (GHRP-2 or KP102) in calves.
AB  - This study was conducted to determine the effects of acute and chronic
      administration of GH-releasing peptide-2 (D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2,
      GHRP-2 or KP102) on GH responsiveness in male Holstein calves. In the dose
      response study of acute administration, six calves were injected iv with saline
      or 6.25, 12.5 and 25.0 micrograms/kg body weight (BW) of KP102. The GH AUC (area
      under curve, ng/ml.min, mean +/- SEM) for 60 min was significantly increased with
      6.25 (676.3 +/- 125.6), 12.5 (1574.8 +/- 318.0) and 25.0 (1578.7 +/- 214.6)
      micrograms/kgBW of KP102 than with saline (78.6 +/- 36.1) (P < 0.01). GH
      responses were decreased by multiple injections of 12.5 micrograms/kgBW KP102 at
      every 2 h for 8 h. The GH AUC for 60 min was decreased from the first injection
      (1162.9 +/- 313.3) to the second injection (604.7 +/- 131.9), but the response
      was significantly higher for the first and second injections than the third
      (304.4 +/- 173.1) and fourth injections (320.7 +/- 144.2) (P < 0.05). In the
      chronic administration, 8 calves were implanted subcutaneously with osmotic pumps
      (Alzet pump). Each of the 4 calves was given with 12.5 micrograms/kgBW per hour
      KP102 and the other 4 calves served as the control. During the 14 day period,
      average daily gain was significantly increased (36.4%) over the control (P <
      0.05). Food efficiency was not significant, but numerically higher (29.4%) than
      the control. The plasma GH concentration was not increased by chronic
      administration of KP102, but IGF-I appeared to increase in KP102-treated calves
      more than the control. These results suggest that the synthetic KP102 can be used
      for enhancing the growth performance in domestic animals.

PMID- 8886624
TI  - A possible common cell surface autoantigen in islet beta-cells and thyroid
      follicular cells in patients with non-insulin dependent diabetes mellitus and
      chronic thyroiditis.
AB  - By an indirect immunofluorescence method with In-111 cells (hamster insulinoma
      cell line), circulating islet cell surface antibodies (ICSA) were detected in 7
      (20%) out of 36 patients with non-insulin dependent diabetes mellitus (NIDDM), 9%
      of 68 chronic thyroiditis (CT) patients, or 16% of 19 NIDDM patients associated
      with CT, but not in 18 normal subjects. Sera from five out of nine ICSA-positive
      patients examined further also showed cell-surface immunofluorescence on TPC-1
      cells (human thyroid papillary adenocarcinoma cell line), and prior absorption of
      the sera with In-111 cells abolished the immunofluorescence. The 64 kDa protein
      from In-111 cells or human thyroid follicular cells was immunoprecipitated with
      ICSA-positive sera. In one case of NIDDM associated with CT, 64 kDa protein was
      detected in both cells. The results indicate that some ICSA in NIDDM patients
      recognize the same or a very closely-related autoantigen(s) in both islet beta
      cells and thyroid follicular cells, suggesting an explanation, at least in part,
      for the autoimmune mechanism(s) in clinical association of NIDDM and CT.

PMID- 8886625
TI  - Effects of surgery on testosterone secretion in male patients with pituitary
      adenomas.
AB  - The purpose of this study was to assess the effect of surgery on gonadal function
      in 42 male patients with pituitary adenomas Gonadal functions were evaluated by
      measuring total serum testosterone concentrations pre- and postoperatively. The
      subjects of the study were 20 patients with GH secreting adenoma, 7 patients with
      prolactinoma and 15 patients with nonfunctioning (NF) adenoma. Their ages ranged
      from 18 to 60 years (mean +/- SEM, 41 +/- 1.9). The serum testosterone
      concentration was low at less than 300 ng/dl preoperatively in 14 of 20 patients
      (70%) with GH producing adenoma, 6 of 7 patients (86%) with prolactinoma, and 7
      of 15 patients (47%) with NF adenoma. Postoperatively, the total serum
      testosterone concentration was normalized in 9 of 14 patients (64%) with GH
      producing adenoma, one of 6 patients (17%) with prolactinoma, and 5 of 7 patients
      (71%) with NF adenoma. The normalization of serum GH and prolactin concentrations
      is indispensable for the restoration of gonadal function. It is very important to
      preserve the normal preoperative gonadotropin secretion by means of gentle
      surgery.

PMID- 8886626
TI  - Insulin stimulates protein synthesis of glycogen synthase in rat hepatoma H4
      cells associated with acceleration of translation rate.
AB  - To assess the regulatory mechanism of insulin action on the biosynthesis of
      glycogen synthase under long-term control, we investigated post-transcriptional
      and post-translational regulation by insulin of glycogen synthase in rat hepatoma
      H4 cells. Glycogen synthase protein gradually increased in response to insulin
      and peaked at 6 h during a 24-h insulin incubation (185% of the control),
      corresponding with the second peak of glycogen synthase activation measured by
      the activity ratio (low glucose 6-P/high glucose 6-P). The effect of insulin on
      synthesis of glycogen synthase protein was assessed by measuring the
      incorporation of [35S]-methionine into the enzyme protein during a 6-h insulin
      incubation. The amount of [35S]-methionine incorporation into glycogen synthase
      was increased in response to insulin with time, and peaked at 4 h (250% of the
      control). The degradation of glycogen synthase examined by measuring the rate of
      reduction of [35S]-methionine for 6 h after the tracer incubation for 12 h was
      not affected by insulin. The results indicate that (a) insulin induces glycogen
      synthase activity by accumulating the enzyme protein due to stimulation of
      protein synthesis rather than inhibition of protein degradation and (b) insulin
      reduced stability of glycogen synthase mRNA is caused by acceleration of the
      translation rate.

PMID- 8886627
TI  - Effects of LHRH, FSH and activin A on follistatin secretion from cultured rat
      anterior pituitary cells.
AB  - We demonstrated the release of follistatin, an activin-binding protein, from
      cultured rat anterior pituitary cells by measuring immunoreactive (ir-)
      follistatin in a specific immunoradiometric assay. Ir-follistatin release
      gradually increased in cultures over 1-18 days and reached its maximal level at
      12-15 days of incubation. The basal ir-follistatin levels in the culture media
      increased about 3- (P < 0.01) and 5-fold (P < 0.001) in 2 and 10% fetal calf
      serum for 6 days, respectively. LHRH and activin A caused an approximately 2.0-
      (P < 0.05) and 1.8-fold (P < 0.05) rise in ir-follistatin release, respectively,
      in contrast to the lack of significant FSH effects. The culture medium condensed
      on sulfate-cellulofine gel was resolved by polyacrylamide gel electrophoresis and
      blotted with anti-follistatin polyclonal antibody, resulting in at least three
      protein bands ranging from 35 to 50 kDa under non-reducing conditions. These
      results indicated that follistatin is produced in anterior pituitary cells and
      that its secretion is regulated at least in part by LHRH and activin, implying an
      autocrine/paracrine role of activin and follistatin in the pituitary.

PMID- 8886628
TI  - Blockade of the estrogen induced increase in progesterone receptor caused by
      propylthiouracil, an anti-thyroid drug, in a transplantable pituitary tumor in
      rats.
AB  - It is well known that estrogen (E2) induces progesterone receptor (PR) in the
      uterus and the mammary gland. In MtT/F84, a pituitary tumor, which was
      established in our laboratory and has been maintained with in vivo passages, we
      investigated the PR regulation by E2 in relation to the host's thyroidal status.
      The PR level in the tumor had increased five fold 48 h after an E2 injection.
      When the host rats were treated with propylthiouracil (PTU), an anti-thyroid
      drug, the induction of PR after an E2 injection was completely blocked. This
      result is consistent with our previous findings indicating that E2 responsiveness
      in the tumor may be under the control of thyroid hormones. The estrogen receptor
      (ER) level in the tumor treated with PTU was 15% of the control. This low ER
      level may account for the blocking of PR induction after an E2 injection. When
      the host animals were continuously treated with various doses of E2, the PR level
      in the tumor rose in correlation with the E2 doses. PTU administration, however,
      did not prevent long term induction of PR by continuous E2 treatment. Our
      findings suggest that PTU lower the ER level and suppresses the short term
      estrogenic actions such as PR induction after an E2 injection.

PMID- 8886629
TI  - A study of anterior pituitary hormones secretion in patients with glioma
      receiving interferon-beta treatment.
AB  - Human interferon beta (IFN-beta) has been used for the treatment of patients with
      benign and malignant astrocytomas. The effect of IFN-beta on pituitary function,
      however, has not been precisely evaluated before. In this study the serum levels
      of various anterior pituitary hormones including GH, PRL, ACTH, and TSH were
      measured to determine the effects of IFN-beta on pituitary endocrine function in
      19 consecutive glioma patients receiving IFN-beta. Daily doses of 3 x 10(6) U of
      IFN-beta were administered as a 30-min intravenous drip infusion beginning at
      0800 h every morning during the first week and then 4 times a week for additional
      6 weeks. Blood samples were taken on the day prior to administration as controls
      (0900 h and 1500 h), and on the first day of administration (0900 h and 1500 h)
      and after 7 days of administration (0900 h) in order to determine the acute and
      chronic or integrated effects of IFN-beta on the above pituitary hormones. No
      significant change in serum concentrations of any of the pituitary hormones
      examined was observed, suggesting that human natural IFN-beta used for the
      treatment of gliomas has no significant effect on the secretion of these hormones
      from the pituitary in these patients.

PMID- 8886630
TI  - Early detection of infants with hypophosphatemic vitamin D resistant rickets
      (HDRR).
AB  - The onset of physical signs in infants with hypophosphatemic vitamin D resistant
      rickets (HDRR) has generally been considered to be at the age of 12 months, but
      the time of appearance of hypophosphatemia and rachitic signs on radiographs
      remains unclear. We report a prospective study in three neonates whose mothers
      were HDRR. At birth, despite a low maternal serum inorganic phosphorus (Pi)
      level, the serum Pi level was normal together with a negligible renal Pi leak in
      one neonate. At age 3 months, their serum Pi levels, percentages of tubular
      reabsorption of Pi, and renal tubular maximal rates of Pi reabsorption in
      relation to the glomerular filtration rate were low except for one infant.
      Radiographically, their rickets were not apparent at birth but at age 3 months in
      all. A premature born infant, born at 28 weeks' gestation weighing 1240 g, was
      diagnosed as HDRR based on hypophosphatemia due to low renal tubular maximal rate
      of phosphorus reabsorption in relation to the glomerular filtration rate
      (TmP/GFR) and normal urine Ca excretion at age 5 months. They were initially
      treated with 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) and later with 1 alpha OHD3
      in combination with Pi, which results in healing of the rickets and a normal
      increase in height. Thus, early detection and treatment of patients born from
      mothers with HDRR before physical signs of bow-leg and short stature is possible,
      but the outcome of early treatment requires further study.

PMID- 8886631
TI  - Biological variation of serum lipids and lipoproteins in patients with clinically
      well controlled non insulin dependent diabetes mellitus.
AB  - To investigate how the visit-to-visit variation in serum lipids measurements
      affects the decision making concerning treatment according to the National
      Cholesterol Education Program (NCEP) guidelines in patients with clinically well
      controlled non-insulin-dependent diabetes mellitus (NIDDM) we have measured the
      biological variation (CVb) in serum total cholesterol (TC), triglycerides (TG),
      high density lipoprotein cholesterol (HDL-C) and low density lipoprotein
      cholesterol (LDL-C) in 26 patients with NIDDM. We found the CVb as follows: TC,
      5.1%; TG, 17.0%; HDL-C 4.4% and LDL-C, 8.3%. Confidence intervals (95%) were
      determined with total intra-individual variance values around the NCEP cut-off
      points to evaluate how well one, two and three lipid measurements provided
      reliable risk classification. A single TC measurements < 177 mg/dL or > 263 mg/dL
      allowed confident classification as "desirable" or "high risk" respectively. For
      LDL-C, one measurement was accurate only at below 106.3 mg/dL or above 183.7
      mg/dL. The average of three measurements contracted these limits to < 186.7 mg/dL
      and > 253.3 mg/dL for TC, and < 116.3 mg/dL and > 173.7 mg/dL for LDL-C. For HDL
      C also, multiple measurements improved risk assignment in a similar fashion.
      There were no values which allowed assignment to the "borderline high" category
      with one TC measurement and with one and two LDL-C measurements. The mean of
      three TC and three LDL-C measurements allowed assignment to the "borderline high"
      category, if between 213.3 and 226.7 mg/dL for TC, 143.7 and 146.3 mg/dL for LDL
      C. Seven patients (26.9%) in this risk group based on the mean of two LDL-C
      estimates could be placed into a different category when the mean of three
      estimates was taken, even though the first two LDL-C test results did not differ
      by more than 30 mg/dL. Our results suggest that repeated lipid measurement is
      important especially for the "borderline-high" risk group because big variations
      existed in some patients, and further that TC is the most reliable quantity.

PMID- 8886632
TI  - Inhibin alpha and beta A subunit messenger ribonucleic acids expression in human
      pituitary adenomas: studies by quantitative reverse transcription-polymerase
      chain reaction.
AB  - Inhibin alpha and beta A subunit messenger ribonucleic acid (mRNA) levels were
      measured quantitatively by reverse transcription-polymerase chain reaction (RT
      PCR) in human pituitary adenomas. The inhibin alpha subunit mRNA levels were
      undetectably low in cultured adenoma tissues, but beta A mRNA were 0.383 +/-
      0.074 in 3 GH adenomas, 0.672 +/- 0.140 in 3 prolactinomas and 0.957 +/- 0.414
      molecules/cell in 3 non-functioning adenomas. The addition of 10(-8) M activin A
      decreased the beta A mRNA levels within 4 h in 1 of 3 GH adenomas, 2 of 3
      prolactinomas and 2 of 3 non-functioning adenomas, though the decreases were not
      statistically significant. The results showed an abundance of beta A subunit mRNA
      compared with alpha subunit mRNA in all human pituitary adenomas and a local role
      for activin in its own production through inhibin beta A mRNA subunit expression.

PMID- 8886633
TI  - Prospective, randomized trial of hypertonic glucose water and sodium tetradecyl
      sulfate for gastric variceal bleeding in patients with advanced liver cirrhosis.
AB  - BACKGROUND AND STUDY AIMS: Information about the appropriate endoscopic treatment
      of gastric variceal bleeding is sparse. We therefore designed a prospective and
      randomized study to evaluate and compare efficacy and complication rates of two
      agents, hypertonic glucose water (50% GW) and sodium tetradecyl sulfate (STS), in
      treating acute gastric variceal bleeding after esophageal varix eradication.
      PATIENTS AND METHODS: Of 51 patients with advanced cirrhosis of the liver
      (Child's C), with acute gastric variceal bleeding initially evaluated, 25
      patients were randomized to receive 1.5% STS and 26 to receive 50% glucose water.
      Treatment was aimed at achieving initial and permanent hemostasis by variceal
      eradication. RESULTS: Control of acute gastric variceal bleeding was achieved in
      80% of the STS group and 92% of the GW group. The rebleeding rate in the STS
      group was 70%, while in the GW group it was 30% (P < 0.05). Overall, obliteration
      was achieved in only 32% of the STS group and 81% of the GW group during
      admission (P < 0.05). There was a trend toward a higher gastric ulcer rate in the
      STS group compared with the GW group (92% vs. 30%; P < 0.05). The rebleeding
      control rate and permanent hemostasis rate in the GW group (70%, 54%) were also
      significantly higher than in the STS group (21%, 12%; P < 0.05; P < 0.05). The
      hospital mortality for the STS group was 50%, and for the GW group 30%.
      CONCLUSION: Treatment with hypertonic glucose water in gastric vericeal bleeding
      was superior to treatment with STS in controlling bleeding and in achieving
      vericeal obliteration, less rebleeding, and a lower complication rate. The
      results of this study suggest that hypertonic glucose water is a clinically
      effective, easily available, and safe sclerosing agent.

PMID- 8886634
TI  - Endoscopic ultrasonographic diagnosis of pancreatic cancer complicating chronic
      pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: Pancreatic cancer is a rare complication of chronic
      pancreatitis (CP), and its diagnosis remains difficult. The present study
      attempted to evaluate the ability of endoscopic ultrasonography (EUS) to diagnose
      pancreatic masses associated with CP and provide evidence of malignancy in
      patients with a pancreatic mass on EUS. PATIENTS AND METHODS: Between 1991 and
      1994, EUS examinations yielded a diagnosis of CP in 85 patients at our
      institution. Forty patients had early CP, 18 had pancreatic pseudocysts
      complicating CP, and 27 had advanced chronic pancreatitis - five of whom were
      considered as presenting pancreatic cancer associated with CP. RESULTS: The five
      patients studied had jaundice, weight loss, and calcifications visible on plain
      abdominal films. Three of them had histological confirmation of pancreatic
      carcinoma. The pancreatic carcinomas were hypoechoic masses of 20-35 mm, with an
      irregular, rounded shape. Calcifications were limited to the periphery of the
      hypoechoic masses. Two patients had negative EUS-guided cytological punctures,
      and are still alive two years later. They were considered as false-positive
      cases. EUS showed a hypoechoic mass with peripheral calcifications in one of
      these false-positive patients, with a large central calcification in the other
      case. The overall sensitivity of EUS for the diagnosis of pancreatic carcinoma
      was 100%, but the positive predictive value was 60%. CONCLUSION: EUS is highly
      sensitive in detecting abnormal masses in cases of CP, but the positive
      predictive value of the diagnosis of pancreatic cancer seems to be weak.

PMID- 8886635
TI  - Assessment of pancreatic parenchymal invasion by bile duct cancer using
      intraductal ultrasonography.
AB  - BACKGROUND AND STUDY AIMS: This study was performed to clarify the diagnostic
      accuracy of intraductal ultrasonography (IDUS) in assessing pancreatic
      parenchymal invasion by bile duct cancer. PATIENTS AND METHODS: Preoperative
      assessment of pancreatic parenchymal invasion was carried out by IDUS via a
      percutaneous tract or a transpapillary route in 18 patients with extrahepatic
      bile duct cancer. Various probes with diameters of 1.4, 2.0, 2.4, 2.6 and 3.2 mm,
      and frequencies of 7.5, 15, 20 and 30 MHz were used. All patients underwent
      angiography and endoscopic ultrasonography (EUS). In the first six cases, IDUS
      and EUS images were analyzed retrospectively without knowledge of the operative
      outcome or the results of other imaging tests. In the subsequent 12 cases, the
      IDUS und EUS images were prospectively reviewed prior to surgery. The diagnostic
      accuracy of IDUS was compared with angiography and EUS by means of a
      histopathological examination of the resected specimens. RESULTS: The accuracy of
      IDUS, EUS, and angiography in assessing pancreatic parenchymal invasion was 100%,
      78% and 61%, respectively. However, IDUS could not assess pancreatic capsular
      invasion. The accuracy of IDUS in assessing horizontal tumor extension to the
      intrapancreatic bile duct and to the hepatic side was 83% and 72%, respectively.
      CONCLUSIONS: IDUS proved useful for assessing the extension of cancer invasion to
      the pancreatic parenchyma, but not to the pancreatic capsule or mucosal surface.

PMID- 8886636
TI  - Nd:YAG laser treatment for bleeding from radiation proctitis.
AB  - BACKGROUND AND STUDY AIMS: Chronic radiation proctitis is a serious complication
      of radiotherapy to the pelvis. It can lead to severe blood loss, and responds
      poorly to surgery or local drug therapy. This study looks at which of the
      patients affected may benefit from endoscopic treatment with Nd:YAG laser.
      PATIENTS AND METHODS: Nine patients who had previously undergone radiotherapy for
      pelvic malignancy a median of 14 months (range 4-43 months) before rectal
      bleeding started were included. Endoscopic Nd:YAG laser treatment commenced a
      median of four months (range 2-13 months) after the onset of blood loss, and was
      repeated monthly until bleeding stopped. Bleeding and transfusion requirements
      were documented before, during, and after a course of laser treatment. RESULTS:
      Patients received an average of three laser treatments (range 1-5). Six had
      received transfusions prior to referral, the average requirement being 1.3 units
      per patient month. Only one patient required transfusion after completion of
      treatment, during an average follow-up of 24 months. Bleeding was reduced to
      occasional spotting in six cases. There were no treatment-related complications.
      Two of the most severely affected patients died within three months of treatment,
      due to recurrence of their underlying malignancy. CONCLUSION: Endoscopic Nd:YAG
      laser treatment is safe and effective for patients with mild to moderate bleeding
      from radiation proctitis.

PMID- 8886637
TI  - Endoscopy databases: the Norwegian experience.
AB  - BACKGROUND AND STUDY AIMS: The implementation of endoscopy databases in Norway
      has been slow, and no commercial system has been successfully introduced.
      MATERIAL AND METHODS: To determine the current status in this area a
      questionnaire survey was conducted with replies received from 58 of the 67
      hospitals to which the questionnaire was sent. RESULTS: Only 40% of the units had
      one or more personal computers available, but video endoscopes will soon be
      standard equipment at most Norwegian hospitals. For managing administrative data,
      a large majority of endoscopy units used a general-purpose hospital information
      system, but endoscopy data are dealt with manually in 72% of the units. The
      endoscopy report itself was produced manually in 93% of the units. When asked to
      rank various features of database systems according to their relative importance,
      the endoscopists stated that ease of use and simplification of routine chores
      were the most important aspects, while advanced storage and research features
      were less crucial. CONCLUSION: In Norwegian hospitals, the use of minimal
      endoscopic database systems that offer a high level of integration with existing
      hospital systems appears to be the most promising approach.

PMID- 8886638
TI  - Laparoscopic cholecystectomy: two-port technique.
AB  - BACKGROUND AND STUDY AIMS: Conventional laparoscopic cholecystectomy requires
      four ports. The present study describes a new laparoscopic cholecystectomy
      technique using two ports only. PATIENTS AND METHODS: Sixty-two consecutive
      patients with symptomatic gallstones underwent laparoscopic cholecystectomy using
      this two-port technique. The operation requires a straightforward laparoscope and
      a percutaneous sling to retract the gallbladder laterally and cephalad. RESULTS:
      The two-port method was successful in 52 patients; eight required an additional
      port, and two required conversion to open surgery. Our results showed that the
      operating time and complication rate were comparable to those in other series
      using the conventional laparoscopic method. CONCLUSION: The two-port method is
      technically more demanding, and should only be used to remove simple,
      uncomplicated gallbladders. The surgeon should always be prepared to insert more
      trocars or convert to open procedures when necessary.

PMID- 8886639
TI  - Miniprobe ultrasonography in the upper gastrointestinal tract: state of the art
      1995, and prospects.

PMID- 8886640
TI  - Self-expanding metallic coil stents for palliation of esophageal carcinoma: two
      cases of decisive stent dysfunction.
AB  - Two cases of different dysfunctions of self-expanding nickel-titanium coil stents
      are described here. In the first case, a metallic coil stent was placed in a 8-cm
      circular rigid stenosis of the mid-esophagus caused by a squamous-cell carcinoma
      (T3 N1 M1), and seven weeks later, the stent lumen was completely occluded by
      massive tumor ingrowth through inadequtely adapted single coil wires. In the
      second case, the caudal and cranial ends of the stent became increasingly
      invaginated after initially adequate stent expansion, resulting in a shortening
      of the stent to about two-thirds of its intended size, with subsequent complete
      luminal obstruction at both ends of the stent due to tumor overgrowth. These two
      examples of different stent dysfunction correspond to similar observations by
      other investigators. Further investigations in a large series of stent insertions
      have to be performed before general conclusion can be drawn as to the clinical
      efficacy of metallic coil stents for endoscopic palliation of esophageal
      carcinoma.

PMID- 8886641
TI  - Two cases of fractured esophageal nitinol stents.
AB  - We report here on two cases of fractured nitinol stents in the esophagus. In case
      1, the correctly inserted stent broke spontaneously shortly after insertion. In a
      second case, a nitinol stent broke after laser application due to tumor ingrowth
      with massive bleeding. In both cases, a second stent was implanted in order to
      reestablish food passage. The fracture of the stent in case 1 seemed to be caused
      by defective material, whilst in case 2 the stent broke because of thermal
      overstrain during laser application. The use of electrocoagulation or laser in
      the stent area should therefore be avoided; argon plasma coagulation may offer an
      effective alternative in treating tumor ingrowth. As there was a risk from
      piercing broken filaments with the second stent, covering a fracture using stents
      with tight walls or plastic tubes seems to be a more effective approach than the
      inserting an uncovered stent type.

PMID- 8886642
TI  - Endoscopic management of obstructive jaundice due to portal cavernoma.

PMID- 8886643
TI  - Endoscopic magnetic resonance imaging of the upper gastrointestinal tract.

PMID- 8886644
TI  - Cardiac tamponade during esophagoscopy.

PMID- 8886645
TI  - Inflammatory esophageal polyp with pseudosarcomatous lesion.

PMID- 8886646
TI  - An unusual endoscopic procedure to remove a toothbrush from the stomach.

PMID- 8886647
TI  - Breakage of an endobiliary metal stent.

PMID- 8886648
TI  - Leadshot: an unusual cause of stent occlusion.

PMID- 8886649
TI  - Endoscopic diagnosis of a duodenocolic fistula due to a non-Hodgkin's lymphoma in
      a patient with AIDS.

PMID- 8886650
TI  - Esophageal ulceration due to alendronate.

PMID- 8886652
TI  - Ileal metastases from malignant melanoma: endoscopic diagnosis.

PMID- 8886651
TI  - Transnasal pharyngoesophagogastroduodenoscopy (T-PEGD) in a patient with acute
      upper gastrointestinal bleeding.

PMID- 8886653
TI  - Balloon dilation of the papilla via a forward-viewing endoscope: an aid to
      therapeutic endoscopic retrograde cholangiopancreatography in patients with
      Billroth-II gastrectomy.

PMID- 8886654
TI  - Acute ischemia followed by hemorrhagic gastric necrosis after injection
      sclerotherapy for ulcer.

PMID- 8886655
TI  - Application of a multiple-band ligator in active variceal bleeding.

PMID- 8886656
TI  - The role of technical, biological and pharmacological factors in the laboratory
      evaluation of anticonvulsant drugs. VI. Seasonal influences on maximal
      electroshock and pentylenetetrazol seizure thresholds.
AB  - There is strong evidence for circadian rhythmicity in certain seizure types,
      whereas only a few studies have addressed the possibility of seasonal rhythms in
      convulsive activity. In the present experiments, seizure thresholds to different
      types of seizures were determined twice per month over a period of 13 months in
      mice under controlled environmental conditions, i.e., constant photoperiod,
      temperature, humidity, and food. Each group of animals was used for only one
      experiment, and the age of the mice used per month was the same throughout the
      study. Furthermore, all experiments were done at the same time in the morning to
      avoid circadian variation. Thresholds for the following seizure types were
      determined: (1) tonic hindlimb seizures induced by electrical (transauricular)
      stimulation; (2) myoclonic seizures induced by intravenous (i.v.) infusion of
      pentylenetetrazol (PTZ); (3) generalized clonic seizures in response to i.v. PTZ;
      and (4) tonic forelimb seizures induced by PTZ. A significant seasonality was
      determined for myoclonic and clonic PTZ seizure thresholds with highest
      thresholds between February and April and lowest thresholds between July and
      September. No clear seasonality was seen for chemically or electrically induced
      tonic seizures. Determination of plasma corticosterone did not disclose any
      seasonal rhythm in adrenal corticosteroid production that resembled the
      circannual variation in myoclonic and clonic seizure thresholds. In conclusion,
      our experiments suggest the existence of seasonal rhythms in PTZ seizure
      thresholds in laboratory animals despite standardized environmental conditions. A
      possible explanation for the findings may be the known seasonal alteration of the
      geomagnetic field which, by its effect on the pineal production of melatonin, may
      act as a seasonal synchronizor ("zeitgeber") in animals in the absence of other
      synchronizing forces, such as seasonal changes in photoperiod and ambient
      temperature.

PMID- 8886657
TI  - Thalamic NMDA transmission in a genetic model of absence epilepsy in rats.
AB  - In the selected strain of GAERS Wistar rats (Genetic Absence Epilepsy Rats from
      Strasbourg), all animals present spontaneously recurrent absence seizures
      characterized by bilateral and synchronous generalized spike-and-wave discharges
      (SWD) accompanied by behavioural arrest. SWD depend on a thalamo-cortical network
      connecting the reticular and relay nuclei of the thalamus and their cortical
      projection areas. This loop involves both GABAergic and glutamatergic synapses.
      In the present study, we investigated the implication of NMDA transmission in the
      genesis of absence seizures in GAERS. Intra-peritoneal or intra
      cerebroventricular injections of NMDA, the competitive NMDA antagonist CGP 40116,
      the non-competitive NMDA antagonist (+)-MK 801 and the antagonist of the glycine
      modulatory site 5,7-dichlorokynurenic acid dose-dependently suppressed SWD.
      Bilateral infusions of the same drugs in the lateral relay nuclei of the thalamus
      had similar suppressive effects. Intra-cerebroventricular or intrathalamic
      administration of D-serine, an agonist of the glycine modulatory site, had no
      effect on SWD. These data show that NMDA neurotransmission, especially within the
      thalamus, plays a major role in the control of absence seizures in GAERs.
      Disregulation of NMDA-mediated transmission by NMDA or antagonists, interacting
      with various sites of the receptor complex, may suppress the thalamo-cortical
      oscillatory activity which underlies SWD.

PMID- 8886658
TI  - Vigabatrin and behaviour disorders: a retrospective survey.
AB  - Vigabatrin is an anticonvulsant drug with a relatively favourable side-effect
      profile. However, in clinical trials behaviour disorders have been reported,
      including agitation, depression and psychoses. In this study, 136 cases of
      behavioural problems that had been reported to the manufacturers, or the authors,
      were followed up. Satisfactory clinical information could be obtained on 81
      patients. Of these, 50 cases met the criteria for either a psychosis (n = 28) or
      depression (n = 22). These were compared with a group of Queen Square patients,
      with epilepsy and psychosis, who had never taken vigabatrin (n = 21) and another
      group, who received vigabatrin without experiencing any behavioural problems (n =
      28). The main results from this study suggest that: (1) Psychosis as a treatment
      emergent effect of vigabatrin is seen in patients with more severe epilepsy,
      compared with those patients who never develop psychopathology, and those
      developing an affective disorder. The psychosis is related to a right-sided EEG
      focus, and suppression of seizures (64% became seizure free). (2) Depression as a
      treatment emergent effect of vigabatrin is associated with a past history of
      depressive illness. There was little or no change in seizure frequency is this
      group. Some suggestions for managing patients who may develop these behaviour
      disorders are given.

PMID- 8886659
TI  - The associations of psychopathology in epilepsy: a community study.
AB  - There is a plethora of studies documenting the association between psychosocial
      disadvantage and epilepsy but a paucity of studies explaining the precise nature
      of that relationship. Previous studies have been hampered by methodological
      problems including small sample size and selection bias. This study examined the
      aetiology of psychopathology in epilepsy in a cross-sectional community study. A
      significant proportion of patients were anxious and depressed and many reported
      side effects of their medication. Stepwise multiple regression techniques were
      employed to examine the relationship between clinical, demographic and
      psychosocial variables. Results indicated that psychosocial variables were the
      best predictors of each other but when these were taken into account, patient
      perceived seizure severity was an important predictor variable in understanding
      the relationship between epilepsy and psychosocial functioning.

PMID- 8886661
TI  - Amygdala-hippocampus relationships in temporal lobe seizures: a phase-coherence
      study.
AB  - We analyzed temporal lobe seizures in patients with intracerebral electrodes to
      assess which of hippocampus and amygdala have a predominant role at seizure
      onset. Seizures were divided into those of mesial temporal onset, in which
      amygdala and hippocampus were involved but the neocortex was not (77 seizures
      from 17 patients), and those of regional onset in which mesial structures and
      neocortex were involved (89 seizures from 16 patients). We measured coherence and
      phase between one amygdala channel and one or two hippocampal channels during the
      first 10 s to determine which structure was leading the discharge. The following
      results are from 33 focal-mesial seizures and 30 regional seizures in which
      amygdala-hippocampus coherence was sufficiently high to measure time delays: the
      amygdala was leading in 21.2% of focal-mesial and 53.3% of regional seizures, and
      the hippocampus was leading in 48.5% of focal-mesial and 26.7% of regional
      seizures (chi-square, P < 0.02); in the remaining seizures, discharges were
      synchronous in the two structures. We conclude that the amygdala is more likely
      to lead when seizures are of regional onset, whereas the hippocampus is more
      likely to lead in focal-mesial seizures. This is probably due to the many
      connections of the amygdala with surrounding temporal neocortex.

PMID- 8886660
TI  - Interictal SPECT of rCBF is of clinical utility in the preoperative evaluation of
      patients with partial epilepsy.
AB  - Fifty-eight patients with drug-resistant partial epilepsy were studied
      preoperatively by interictal rCBF measurements using 99mTc-HMPAO and a dedicated
      brain SPECT camera (Tomomatic 64). Follow-up of seizure outcome, using the "Engel
      score", was at least 3 years. The data were analyzed in a blinded set-up, first
      visually and subsequently quantitatively by an automatic regional analysis. By
      visual analysis 95% of the patients were considered abnormal in one part of the
      brain, of whom 27% were abnormal on CT, 45% on MRI and 98% on scalp EEG. Using a
      quantitative regional analysis subdividing each hemisphere into 17 larger
      regions, 85% of the patients had an abnormal rCBF compared to an age-matched
      control population of healthy volunteers (using the Wilcoxon 2-sample test with
      Bonferroni's correction). The average number of abnormal regions of interest was
      4.7. The percentage of patients with abnormal SPECT-CBF or the total number of
      abnormal regions of interest (ROIs) per patient showed no correlation to duration
      of epilepsy or seizure load (number of seizures per year x epilepsy duration) or
      seizure type. Neither were the rCBF changes prognostic for the outcome as
      measured by the Engel score. In 20 patients ictal SPECT of rCBF was additionally
      performed. In 2 cases it added further information to the patient evaluation.

PMID- 8886662
TI  - Effects of high-dose antiepileptic drugs on event-related potentials in epileptic
      children.
AB  - N200 and P300 of event-related potentials (ERPs) were recorded from 22 epileptic
      children receiving high-dose antiepileptic drugs. The patients were undergoing
      monotherapy with supratherapeutic serum level and were not mentally retarded.
      P300 latency was prolonged in 5 of 8 patients (62.5%) of the carbamazepine (CBZ)
      group and in 4 of 7 patients (57.1%) of the phenytoin (PHT) group. Only one child
      of the PHT group showed abnormality in brain-stem auditory evoked potentials
      (BAEPs). Abnormality of P300 was more frequent than that of BAEP. In patients of
      the PHT group who underwent examinations consecutively before and after changing
      the dose, P300 latency was prolonged rapidly when the PHT level exceeded 30
      micrograms/ml. This suggested that the prolongation was dose dependent. In all
      patients of the valproic acid (VPA) group, P300 latency was normal. Only 2
      patients of the PHT group had P300 prolongation simultaneously with clinical
      signs of intoxication. Others demonstrated changes in P300 without symptoms of
      side effects.

PMID- 8886663
TI  - Teleconsultation: a new neurosurgical image transfer system for daily routine and
      emergency cases--a four-year study.
AB  - In January 1991, an image transfer unit was developed and installed in the
      neurosurgical department of the University in Mainz. The system provides an image
      transfer of patient data via fibreoptic cable networks (VBN), ISDN, and public
      telephone line. In the following 4 years, 432 consultations were recorded. Nine
      departments were linked within this system. They provided an emergency out
      patient department for primary treatment and radiology. The lack of a
      neurosurgical department in these clinics was made up for by the image transfer
      system. In these rural medical departments, teleconsultation improves the care of
      daily routine neurosurgical cases, as well as in emergency cases. There is also a
      decrease of costs due to teleconsultation. The image transfer via simple public
      telephone line was sufficient.

PMID- 8886664
TI  - Cardiac dysrhythmias in severe verapamil overdose: characterization with a canine
      model.
AB  - Verapamil overdose, because of its frequency and severity, represents a
      significant problem for the emergency physician. With recent search recommending
      specific therapies for verapamil toxicity, aids to rapid diagnosis hold promise
      for decreasing morbidity and mortality from overdose of all calcium channel
      blockers. At this time, diagnosis of verapamil toxicity depends primarily on
      patient history and identification of cardiac dysrhythmias. This study attempts
      to improve the diagnostic armamentarium available for verapamil poisoning by
      analysing cardiac conduction problems seen in a canine model of verapamil
      toxicity, with the goal of identifying clinically useful dysrhythmia patterns. In
      43 verapamil-toxic animals, junctional rhythm without organized atrial activity
      was the most frequently identified rhythm (55.6%). The next most commonly seen
      rhythms were tertiary atrioventricular (AV) block (16.3%) and idioventricular
      rhythm (11.6%); other animals manifested low grade AV block. Of interest,
      prominent U waves were noted in 25.6% of animals. While these results are subject
      to the limitations inherent in the use of an animal model, the data generated
      provide potentially useful patterns of dysrhythmia which may be encountered in
      humans with verapamil toxicity.

PMID- 8886665
TI  - Patients with psychiatric emergencies transported by an ambulance in an urban
      region.
AB  - This paper studies the use of an ambulance service in the case of psychiatric
      emergency referrals. A cross-sectional design was used to compare the patients
      brought in by an ambulance with all other psychiatric emergency referrals. The
      sociodemographic and clinical characteristics as well as the referral pattern of
      both groups of patients are compared. Results show that an important proportion
      of patients brought in by an ambulance can be described as high risk referrals.
      However, for another group of referrals the ambulance is used for other reasons.
      The possibility of using alternative social services in these cases are
      discussed.

PMID- 8886667
TI  - What did we learn from the time registration in the Belgian Cardio-Pulmonary
      Cerebral Resuscitation registry?
AB  - It is well known that in a case of cardiac arrest a fast intervention is
      essential for the survival of the victim. All research on resuscitation therefore
      contains some reference to intervention times. In the past it was difficult to
      compare the results of different studies. This problem has however been overcome
      by the publication of the Utstein Guidelines, as these guidelines emphasize on a
      correct and complete time registration with uniform definitions of the different
      time intervals. As the Belgian Cardio-Pulmonary-Cerebral Resuscitation Study
      Group tries to collect all these time intervals we are able to present the
      complete performance of the interventions for cardiac arrest of five registration
      centres and to identify weak points in our 'chain of survival'.

PMID- 8886666
TI  - Systemic and cerebral oxygen extraction after human cardiac arrest.
AB  - The aim of this study was to observe cerebral and systemic oxygen extraction
      after human cardiac arrest with return of spontaneous circulation. Eight adult
      patients after non-traumatic, cardiac arrest were included. Cerebral and systemic
      oxygen extraction ratios were measured together with haemodynamic variables
      beginning 2 hours after cardiac arrest and every 4 hours thereafter until 24
      hours. Between 2 and 12 hours after cardiac arrest cerebral oxygen extraction
      values ranged from very low over normal to very high. In the further course these
      values were reduced until 24 hours in six patients. Two patients who were still
      alive after 6 months, both severely mentally disabled, had a higher cerebral
      oxygen extraction ratios in comparison with non-survivors. Systemic oxygen
      extraction seemed to vary more than the cerebral oxygen extraction. The two long
      term survivors had normal to supranormal values from 8 to 24 hours. In conclusion
      cerebral oxygen extraction was higher in long-term cardiac arrest survivors than
      in non-survivors between 12 and 24 hours after the event. Further, a better
      quality of neurological recovery was associated with higher cerebral oxygen
      extraction. Systemic oxygen extraction was also impaired, but to a lesser extent,
      especially in long-term survivors.

PMID- 8886668
TI  - Re-admissions among patients with acute chest pain who were discharged from the
      emergency department.
AB  - This paper describes the rate of re-admission and the characteristics of patients
      who were re-admitted after having been discharged directly from the emergency
      department at Sahlgrenska Hospital when they presented with acute chest pain or
      other symptoms suggestive of acute myocardial infarction. A total of 1463
      patients were admitted and directly discharged during the 15 month recruitment
      period, of whom 222 (15%) were re-admitted at least once and 72 (5%) were re
      admitted more than once during the subsequent 6 to 21 months. However, among
      patients not being re-admitted, 63% reported recurrency of symptoms one year
      after discharge. Re-admitted patients differed from those who were not re
      admitted by: being older (p < 0.001); they more frequently had a history of
      cardiovascular diseases (p < 0.001); they more frequently had a pathological
      electrocardiogram (p < 0.001); and they were more frequently judged to have
      angina pectoris (p < 0.001). Among re-admitted patients, about half were
      hospitalized but only 10% developed AMI. In conclusion, among patients who were
      discharged directly from the emergency department with acute chest pain, 15% were
      re-admitted with similar symptoms only. A minority, however, developed acute
      myocardial infarction. A high proportion of patients not being re-admitted had
      recurrency of symptoms.

PMID- 8886669
TI  - Traumatic blunt carotid injury: clinical experience and review of the literature.
AB  - To evaluate the symptoms, the associated lesions, the treatment and the outcome
      of patients with blunt carotid injury (BCI), we reviewed the records of all
      patients admitted to our intensive care unit with head trauma between May 1991
      and May 1995. A patient's assessment included the commonly used severity scores
      and cranial computed tomography (CT). Other diagnostic investigations were
      performed according to the clinical setting. Four patients (2 males, 2 females,
      age 29 +/- 13 years) out of 145 were diagnosed to have BCI. At admission, the
      Glasgow Coma Scale (GCS) was > or = 12 in all patients, and was associated with
      hemiparesis in three of them; the fourth became paretic 48 hours later. No
      pathological elements were demonstrated at the initial CT scan, whilst subsequent
      examinations showed signs of ischaemia after a variable interval from admission.
      In every patient the radiologic investigations demonstrated a thrombotic
      obstruction of the internal carotid artery (ICA), associated with an intimal
      dissection in two cases. Three patients were discharged with only minor
      neurologic symptoms. The fourth patient was referred to our ICU after the
      development of a massive hemispheric infarction, and died 3 days after admission.

PMID- 8886670
TI  - Maxillofacial injuries in the multiply injured.
AB  - A survey of patients with maxillofacial injuries (MFI) was carried out in a
      triaged cohort of multiply injured patients (n = 802) evacuated from accident
      scenes by the helicopter emergency medical service (HEMS). Despite intubation at
      accident scenes, some patients required further airway protection on arrival at
      hospital. One hundred and ninety-six patients (24.5%) had MFI and 90 (11.2%) were
      classified as severe with ISS of facial region > 2 or more severe (ISS up to 16,
      median 4). The latter group were commonly found to be associated with other
      severe injuries (median ISS of 36) leading to death in 41 patients (5.1% of the
      total). Out of the 196 multiply injured patients with MFI, 57 (29%) had
      diagnostic peritoneal lavage for suspected haemorrhage, 27 (14%) subsequently
      underwent laparotomy. Six (3%) had thoracotomies and 29 (15%) had chest drains
      inserted. Seventeen (9%) had emergency craniotomies and 14 (7%) required
      intracranial pressure monitoring. Orthopaedic injuries were most commonly
      associated with MFI and 91 patients (46%) underwent surgical interventions. The
      purpose of the present study was primarily to establish a database for MFI
      patients with multiple injuries. The longer term objective being to gain evidence
      for early definitive management of these complicated cases rather than the more
      traditional expectant policies. In our view delayed management of MFI can rarely
      correct all the consequent facial deformities.

PMID- 8886671
TI  - Overuse of emergency care in psychiatry?
AB  - In an open study relating psychiatric emergencies in a general hospital, the
      authors observe that only in 30% of cases does the reason for emergency referral
      of patients by their general practitioner involve the concept of danger. In view
      of the results of this study, it would seem beneficial, if one wishes to reduce
      the number of psychiatric admissions, to improve the training of general
      practitioners in general psychiatry and in the treatment of mood disorders in
      particular.

PMID- 8886673
TI  - How safe is Biers Block in the accident and emergency department?
AB  - We report on the use of Biers Block in an accident and emergency department
      carried out during the period 1987 to 1994. A total of 915 procedures were
      carried out, of which 815 (98%) involved emergency procedures. The age of
      patients ranged between 17 and 92 years. Acceptability by the patients was
      uniformly good. We feel it is a useful method of producing analgesia in the limb
      that does require training but no extensive experience or anaesthetists'
      expertise.

PMID- 8886672
TI  - Combined intoxication with a tricyclic antidepressive agent and a neuroleptic.
AB  - We report the case of a patient who co-ingested a tricyclic antidepressant (2500
      mg of doxepin) and a neuroleptic drug (3500 mg of prothipendyl). Following
      overdose either agent can affect the central nervous and cardiovascular systems,
      inducing arrhythmias, conduction disturbances and hypotension. The presented case
      illustrates that a combined overdose of tricyclic antidepressants and
      neuroleptics enhances the possible toxic effects of each drug and especially the
      risk for adverse cardiac events. The clinical features and management of this
      combined intoxication are discussed. Treatment with sodium bicarbonate readily
      corrected a potentially life-threatening cardiac arrhythmia and is therefore
      suggested to be imperative in the treatment of these cases.

PMID- 8886674
TI  - Hypothermia in trauma patients.

PMID- 8886675
TI  - Fetal sensory competencies.
AB  - A growing body of evidence is available about the functioning of fetal sensory
      systems during gestation. This article aims at reviewing data concerning (i) the
      presence of potential sensory stimulation in the fetal milieu, (ii) the
      sequential functional development of the sensory systems and (iii) physiological
      and behavioral responses of fetuses to various types of stimulation. Human data
      are compared with data collected in other mammalian species. Most studies have
      investigated auditory and chemosensory (olfactory and gustatory) responsiveness
      of the fetus in the second half of gestation. They demonstrate that (i) motor and
      heart rate responsiveness depends on gestational age and characteristics of
      stimulation; (ii) fetal sensory experience has short- and long-term effects at
      morphological, functional and behavioral levels (for example transnatal
      learning). The clinical consequences of the fetal sensory functioning are
      developed.

PMID- 8886677
TI  - Uterine anomalies and in vitro fertilization: what are the results?
AB  - OBJECTIVE: To evaluate the influence of uterine anomalies on the implantation
      rates after embryo transfer. STUDY DESIGN: A retrospective, multicentric study.
      This study compare patients presenting a uterine anomaly (septate uterus,
      umicornuate, pseudonicornuate, bicornuate uterus) having attempted FIVETE between
      1987 and 1992 with the normal population treated by IVF, as well as with FIVNAT
      results. RESULTS: Thirty-eight patients were part of the studied population and
      total 119 oocyt retrievals which lead to 103 embryo transfers (corresponding to
      1.35% of the realised transfers during the same period in the three centers of
      the study). The pregnancy rate obtained by these patients is significantly lower
      than those obtained by the control group (11.7% pregnancies by retrievals vs.
      19.1%, and 13.6% pregnancies by transfer vs. 24.9%). The implantation rate by
      embryo transfer is 5.8% in the population studied vs. 11.7% in the control group
      (P < 0.01). These results significantly improve when the uterine anomaly can be
      treated (septate uterus). CONCLUSION: The uterine anomalies are associated with a
      lowered rate of embryo implantation. This implantation rate improves when the
      anomaly can be treated (septate uterus).

PMID- 8886676
TI  - Is maternal serum creatine kinase actually a marker for early diagnosis of
      ectopic pregnancy?
AB  - OBJECTIVE: Our purpose was to investigate whether serum creatine kinase (CK)
      levels could be used as an early marker of ectopic pregnancy. Student's t-test
      was used for statistical analysis. STUDY DESIGN: In a prospective study we
      therefore measured serum progesterone, beta hCG and CK levels in 30 women with
      ectopic pregnancies, 30 women with ongoing pregnancies and 30 women with missed
      abortion. RESULTS: The mean serum CK concentration for patients with an ectopic
      pregnancy, ongoing pregnancy, and the women with missed abortion was 81.4 +/-
      66.2, 81.5 +/- 40.3, 84.8 +/- 49.3, respectively. No relationship was found
      between CK level and the location of the pregnancy. CONCLUSION: Conversely to the
      first report of Lavie et al. (Am J Obstet Gynecol 1993; 169: 1149), our data
      suggest that serum CK level is not discriminative in the early diagnosis of tubal
      pregnancy.

PMID- 8886678
TI  - Prostanoid production in umbilical vessels and its relation to glucose tolerance
      and umbilical artery flow resistance.
AB  - OBJECTIVE: To study prostanoid synthesis in umbilical vessels relative to
      maternal glucose tolerance and umbilical artery blood flow resistance. STUDY
      DESIGN: Umbilical artery pulsatility index was determined by Doppler velocimetry
      in 21 women with diabetes or impaired glucose tolerance and 10 healthy women.
      Segments from the umbilical artery and vein were incubated and prostacyclin
      (PGI2) and thromboxane (TxA2) metabolites determined. Statistical analyses with
      the Mann-Whitney U test, Kruskal-Wallis test, Wilcoxon signed-ranks matched-pairs
      test, contingency table analysis, Fisher's exact test, and simple linear
      regression analysis were used and a two-tailed P value of < 0.05 considered
      statistically significant. RESULTS: No significant difference in PGI2 or TxA2
      production was found in umbilical vessels between the women with
      diabetes/impaired glucose tolerance and controls, but the PGI2/TxA2 ratio in the
      vein was significantly lower in the diabetes/impaired glucose tolerance group.
      The umbilical artery pulsatility index was positively correlated to the PGI2/TxA2
      ratio in cord vessel segments and to cord plasma TxA2 concentration. The cord
      plasma TxA2 concentration was significantly higher in cases with a high umbilical
      artery pulsatility index. The prostanoid production was not correlated to
      maternal HbA1c or cord plasma C-peptide concentrations. CONCLUSIONS: In
      association with diabetes, an increased 'peroxide vascular tone' and an enhanced
      'endoperoxide shift' between platelets and vascular endothelium may explain the
      unexpected positive correlation found between the umbilical artery pulsatility
      index and the vascular PGI2/TxA2 synthesis ratio.

PMID- 8886679
TI  - Thyrotropin releasing hormone and corticosteroids prior to preterm labour: a
      survey of current practice in nine European countries. European Union Antenatal
      TRH Network Steering Committee.
AB  - There is considerable variation in the use of cortisosteroids within Europe
      before possible preterm delivery. Thyrotropin releasing hormone is rarely used as
      synergistic treatment in most, but not all, European countries-presumably
      reflecting uncertainty about the effectiveness and safety of this agent.

PMID- 8886680
TI  - Maternal and neonatal hyponatraemia: a comparison of Hartmanns solution with 5%
      dextrose for the delivery of oxytocin in labour.
AB  - We performed a randomised controlled trial to compare the effect on neonatal and
      maternal serum sodium of using oxytocin in Hartmanns solution compared to the
      standard 5% Dextrose regimen for induction or augmentation in labour. We found
      significantly decreased maternal and neonatal serum sodium concentrations in the
      5% Dextrose group compared to the Hartmanns group.

PMID- 8886681
TI  - Prenatal care and sea fish.
AB  - OBJECTIVES: To evaluate the effects of a prenatal nutritional counselling
      programme about the benefits of increasing dietary intake of sea fish. STUDY
      DESIGN: A hospital and parity matched observational comparison study. Four
      hundred ninety-nine pregnant women, attending selected clinics for antenatal
      care, before 20 weeks gestation, were offered a 20-min nutritional advice
      session. They were encouraged to increase the intake of oily sea fish and reduce
      intake of food rich in transfatty acid. For each woman interviewed a
      corresponding control was established. MAIN RESULTS: The mean birth weight was
      slightly higher in the study group (3349 g vs. 3284 g) and the difference
      persisted after adjusting for gestational age (85 g/week vs. 83 g/week). The rate
      of delivery before 37 weeks was lower in the study group (7.3% versus 9.5%). The
      mean neonatal head circumference was greater in the study group (34.7 cm vs. 34.4
      cm). CONCLUSION: The effect of advice to increase intake of oily fish warrants
      further study.

PMID- 8886682
TI  - Anaemia in pregnancy--is the current definition meaningful?
AB  - OBJECTIVE: To determine if the current definition of antenatal anaemia
      (haemoglobin < 10 g/dl) has any clinical significance. STUDY DESIGN: A
      retrospective study on all singleton deliveries over a 3-year period in two
      teaching hospitals under one university department was conducted by the
      extraction of data from a computer database. The major pregnancy complications
      and perinatal outcome were compared between mothers with and without anaemia and
      adjusted for parity. RESULTS: The incidence of multiparity was significantly
      higher in the 817 anaemia patients compared to the 10125 non-anaemia patients,
      but there was no difference in the incidence of other major antenatal
      complications, type of labour or mode of delivery, incidence of preterm delivery,
      or perinatal mortality or morbidity, after adjusting for parity. Among the
      anaemia patients, those with thalassaemia trait (54.8%) had a significantly
      higher incidence of gestational glucose intolerance but the incidences of other
      complications and the perinatal outcome were similar to the iron deficiency
      patients. CONCLUSION: Antenatal anaemia, defined as a maternal haemoglobin of <
      10 g/dl, does not adversely affect pregnancy outcome. This raises the question of
      whether the diagnosis of anaemia should be redefined.

PMID- 8886683
TI  - Proteases and their inhibitors are indicative in gestational disease.
AB  - OBJECTIVE: To assess whether various proteolytic factors which are involved in
      trophoblast invasion show different concentrations in plasma and placenta of
      patients with HELLP syndrome, pre-/eclampsia and highly pathological Doppler flow
      measurements but without additional complications (hpD). DESIGN: Case control and
      observational study; 18 women with HELLP syndrome, 21 with pre-/eclampsia, 13
      with hpD, as well as healthy pregnant women (matched pairs); statistical
      analysis: sign test and Wilcoxon test. RESULTS: Urokinase-type plasminogen
      activator (uPA), uPA receptor, tissue-type plasminogen activator (tPA),
      plasminogen activator inhibitor 1 (PAI-1), matrix metalloproteinases MMP-8, MMP-9
      and tissue inhibitor of metalloproteinases TIMP-1 were measured by ELISA. PAI-1
      plasma levels are significantly elevated in all three groups studied. In HELLP
      syndrome, tPA and TIMP-1 are also elevated, and in patients with hpD, MMP-8 is
      increased, whereas MMP-9, and TIMP-1 are lower. In placenta extract, only pre
      /eclampsia shows reduced MMP-9 concentrations. CONCLUSIONS: The increased
      frequency of small-for-gestational-age infants observed in all three study groups
      is an expression of impaired placental implantation and remodelling processes.
      These disturbances manifest themselves in the form of changes in some of the
      factors in plasma and placenta extract that are involved in these processes.

PMID- 8886684
TI  - Antenatal care in pregnancies at risk of alloimmune thrombocytopenia: report of
      19 cases in 16 families.
AB  - OBJECTIVE: To assess accuracy of a management program in patients at risk for
      alloimmune thrombocytopenia (NAITP) and to describe perinatal outcomes. STUDY
      DESIGN: Nineteen fetuses at risk of thrombocytopenia were identified using
      obstetric history, HLA type of the mother and fetal phenotyping in cases where
      paternal heterozygozity for the offending antigen was present. Cordocentesis was
      timed according to obstetric history and performed with safety precautions to
      prevent haemorrhage. High dose intravenous gamma globulin (IVIG) was administered
      to the mother in cases with a fetal platelet count < 100 x 10(9)/l. RESULTS: The
      platelet antagonisms were distributed as follows: HPA-1a in 15 patients, HPA-5a
      in two, HPA-3a in one, with one further woman who had antibodies against a
      private antigen. All multigravidas (N = 18) had previously given birth to an
      infant with NAITP and two of those infants had experienced severe bleeding. Two
      fetuses were negative for the offending antigen. The median and mean platelet
      count at first cordocentesis was 26 and 75 x 10(9)/l respectively (range 3-276).
      A total of 46 cordocentesis were carried out, of which 37 were followed by
      platelet transfusions. Bleeding complications were not observed. IVIG was
      administered to eight mothers and two fetuses responded. Nine infants were
      delivered by caesarean section (CS) and 10 vaginally at a mean gestational age of
      37 weeks (range 34-41). The median and mean platelet count at birth was 141.5 and
      140 x 10(9)/l, respectively (range 36-314). Ultrasound examination, both ante-
      and postnatally, revealed no intracranial haemorrhages. There was one procedure
      related neonatal death and one infant suffered from convulsions in the neonatal
      period due to a sinus thrombosis, possibly related to the platelet transfusions.
      CONCLUSIONS: When obstetric history is taken into account cordocentesis in NAITP
      can be postponed. Safety recommendations described in this study allow
      cordocentesis without bleeding complications. However, our study does not support
      routine cordocentesis in patients with a history of NAITP. Both the risks of
      cordocentesis, and the lack of prospective data on the magnitude of the risk of
      intrauterine or peripartal bleeding, should be considered.

PMID- 8886685
TI  - Patterns of villous and intervillous space growth in human placentas from normal
      and abnormal pregnancies.
AB  - OBJECTIVES: To apply a new stereological approach (relating an exponent of
      villous surface to volume) to test for patterns of change in placental villi and
      intervillous space from normal and abnormal pregnancies. STUDY DESIGN: Placentas
      from normal gestation and pregnancies associated with hypoxic stress (high
      altitude, diabetes, cigarette smoking) were sampled randomly, fixed in formalin
      and embedded in paraffin wax for stereological analysis. Volumes (villi,
      intervillous space) were estimated by point counting and surface areas (villi) by
      intersection counting. A dimensionless coefficient (S3/2/V) was then calculated
      to test for isomorphic changes. Comparisons within groups were drawn using
      analysis of variance. RESULTS: Changes in villi were isomorphic at high altitude
      and in placentas from women who smoked during pregnancy. The same pattern is seen
      in placentas associated with preeclampsia. Changes during gestation and diabetes
      are anisomorphic, i.e. villous surface area alters disproportionately to volume.
      A similar pattern is seen in maternal anaemia. Alterations in the intervillous
      space were isomorphic in diabetes and smoking but anisomorphic during gestation,
      at high altitude and in maternal anaemia and pre-eclampsia. CONCLUSIONS: The
      approach has advantages over alternatives (star volume and topological analysis).
      Structural changes influence placental transport and haemodynamics but there are
      subtle differences between groups which may depend on the nature of the hypoxic
      stress and the adaptations made by individual tissue compartments.

PMID- 8886687
TI  - The potential impact of PR interval analysis of the fetal electrocardiogram
      (FECG) on intrapartum fetal monitoring.
AB  - A retrospective study was performed at the Queens Medical Centre, Nottingham, UK
      to evaluate the potential value of PR interval analysis of the FECG compared to
      conventional intrapartum assessment with fetal heart rate monitoring. Two-hundred
      sixty-five labours were selected for monitoring. Outcome was assessed by the
      number of fetal scalp blood samples (FBS) performed and the associated incidence
      of acidosis in the first stage of labour, the mode of delivery and whether or not
      this was expedited for fetal heart abnormality or an abnormal scalp pH. The
      condition of the fetus at delivery was assessed by arterial and venous blood acid
      base status, Apgar score and the need for admission to the neonatal intensive
      care unit. Conventional electronic fetal heart rate monitoring (EFM) was used in
      all labours. The addition of PR interval assessment would potentially reduce the
      numbers of normal FBSs being carried out from 85.5% to 26.8% and the proportion
      of cases of missed acidosis at delivery from 8.5% to 4.5%. These results
      highlight the potential benefit of PR interval analysis in improving
      interpretation of the intrapartum cardiotocograph and need to be tested by
      prospective randomised controlled study.

PMID- 8886686
TI  - Fetal heart rate tracings: observers versus computer assessment.
AB  - Cardiotocography (CTG) is widely used despite the fact that its diagnostic
      accuracy is far from satisfying. This is due, among other reasons, to the great
      intra- and interobserver variation in reading the fetal heart rate tracings.
      Computerized analysis might be a means to overcome the latter problem. OBJECTIVE:
      the present study was designed to assess the reproducibility of CTG readings
      among observers and between observers and a computer system. STUDY DESIGN: 63
      fetal heart rate tracings were read by 4 clinicians (2 experienced and 2
      inexperienced) and by the 2CTG computerized system. The variables considered
      were: baseline fetal heart rate (FHR), long-term variability (amplitude bandwidth
      around the baseline), number of large accelerations and number and type of
      decelerations. RESULTS: the agreement among observers, assessed by means of kappa
      coefficient, ranges from fair to good. The agreement between each of the
      observers and the computer readings, ranges from 0.18 to 0.48 for FHR baseline,
      from 0.16 to 0.74 for variability, from 0.37 to 0.64 for the number of
      accelerations and from 0.41 to 0.54 for the number of decelerations. The
      agreement on the type of decelerations is very low (0.01-0.25). CONCLUSION: it is
      concluded that interobserver variability between experienced observers,
      inexperienced observers and 2CTG is considerable and that the use of a computer
      system should overcome this problem.

PMID- 8886688
TI  - Low incidence of congenital toxoplasmosis in children born to women infected with
      human immunodeficiency virus. European Collaborative Study and Research Network
      on Congenital Toxoplasmosis.
AB  - In children born to immunocompetent women, congenital toxoplasmosis almost always
      results from primary infection during pregnancy. However, reactivation of latent
      toxoplasmosis during pregnancy could occur in HIV-infected pregnant women,
      particularly in those who are severely immunocompromised, and result in maternal
      fetal transmission of the parasite. This mode of infection has been described in
      case reports but the risk of transmission is unknown. Findings on toxoplasmosis
      are presented from the European Collaborative Study, a prospective study of
      children born to women known to be HIV-infected at the time of delivery. In 1058
      children followed for a mean duration of 35 months, only one child developed
      clinical toxoplasmosis. This child was HIV-infected, severely immunocompromised,
      and acquired toxoplasmosis postnatally. Congenital infection was excluded
      serologically in a subgroup of 167 children, of whom an estimated 71 had been at
      risk of infection. These clinical and serological findings indicate a low general
      risk of maternal-fetal transmission of Toxoplasma infection in HIV-infected
      women. It is not possible to draw conclusions about the risk of transmission for
      severely immunocompromised HIV-infected women because most women in the study
      were asymptomatic.

PMID- 8886689
TI  - Large differences in obstetrical intervention rates among Dutch hospitals, even
      after adjustment for population differences.
AB  - Within the framework of the 'Obstetric Peer Review' project (Verloskundige
      Onderlinge Kwaliteitsspiegeling, VOKS) statistical models have been developed to
      predict department specific intervention rates, based on the distribution of risk
      factors in each department. Subsequently the difference between the expected
      number of interventions (labour inductions, caesarean sections and vaginal
      operative deliveries) and the actual numbers were calculated for each year and
      subpopulation defined by the level of prematurity. Data used were available from
      the Perinatal Database of the Netherlands (Landelijke Verloskunde Registratie,
      LVR) concerning the years 1988-1992. Even after adjusting for many clinical risk
      factors the interdepartmental differences of intervention rates are both
      clinically relevant and statistically significant. It was also obvious,
      especially for the term population, that departments showed a consistent pattern
      with respect to the difference between their expected and observed intervention
      rates over these 5 years.

PMID- 8886690
TI  - Immunohistochemical localization of tissue inhibitor of metalloproteinases-2
      (TIMP-2) in first trimester human placental decidua.
AB  - BACKGROUND: Matrix metalloproteinases have been shown to play an important role
      both in the invasive growth of malignant tumors and in human placentation.
      However, unlike tumor cell invasion, cytotrophoblast invasion is strictly
      controlled in its extent. Tissue inhibitors of metalloproteinases (TIMP) may play
      an important role in the modulation of cytotrophoblast growth into maternal
      tissue. STUDY DESIGN: We have undertaken an immunohistochemical study of the
      distribution of TIMP-2 in the decidua of first trimester human pregnancy.
      RESULTS: Moderate to strong staining for TIMP-2 was found in decidual stromal
      cells and the walls of blood vessels in all cases. No unequivocal staining of
      decidual leukocytes was seen. CONCLUSION: These findings suggest that TIMP-2
      secretion in first trimester human decidua is confined to certain cell
      populations. Decidual stromal cells are probably an important source of TIMP and
      may contribute to the regulation of human cytotrophoblast invasion in vivo.

PMID- 8886691
TI  - Corticotropin-releasing-hormone levels in pregnancy-induced hypertension.
AB  - High levels of corticotropin-releasing hormone (CRH) circulate in the plasma of
      pregnant women especially during the third trimester and even higher levels have
      been reported in abnormal pregnancies of various etiologies. One of these
      etiologies is pregnancy-induced hypertension (PIH). OBJECTIVE: To measure CRH
      blood levels with a sensitive method in a large number of pregnant women with
      PIH, starting from very early stages of gestation, and to compare them with those
      in normal controls. STUDY DESIGN: Venous blood was withdrawn from, (a) 10 healthy
      women aged 20-35 years, (b) 62 pregnant women with PIH (109 samples), mean age
      29.1 years and (c) 75 healthy pregnant women (81 samples), mean age 28.5 years,
      used as matched controls. In pregnant women, blood collection started at the 10th
      week of gestation. In 14 women from group b and in 22 from group c blood was
      withdrawn during labor as well. CRH was assayed by RIA. RESULTS: Levels in non
      pregnant women were between 19.0-40.6 pg/ml (28.37 +/- 2.53 pg/ml, mean +/-
      S.E.M.). In both groups of pregnant women there was a progressive increase in
      plasma CRH levels becoming quite sharp towards the end of gestation. Between 10
      and 20 weeks, CRH (mean +/- S.E.M.) in PIH group was 69.3 +/- 3.2 pg/ml versus
      41.6 +/- 2.4 pg/ml in matched controls, at 21-25 weeks 168.0 +/- 12.8 pg/ml
      versus 58.5 +/- 3.8 pg/ml, at 32-35 weeks 1378.5 +/- 61.4 pg/ml versus 298.3 +/-
      16.9 pg/ml and at 38 weeks 2800.0 +/- 114.1 pg/ml versus 825.0 +/- 59.8 pg/ml. At
      term, CRH levels were 3784.0 +/- 197.3 pg/ml in PIH, versus 1386.0 +/- 101.8
      pg/ml in normal pregnancy. Statistically, at every stage of gestation, CRH levels
      were highly significantly different in the PIH group (P < 0.0005). One hour
      postpartum there was a c. 60% decrease in plasma CRH levels in both b and c
      groups. In three women with pre-eclampsia who underwent premature labor due to a
      dead fetus around the 30th week, very high levels were noticed in sequential
      blood samples for 4-5 weeks prior to labor. CONCLUSIONS: (a) CRH levels in women
      with PIH are significantly higher compared to healthy pregnant women at any stage
      of gestation starting from week 10; (b) very high levels during pregnancy might
      be predictive of premature labor or fetal loss; and (c) CRH measurement might
      prove to be a helpful diagnostic tool in women with pregnancy-induced
      hypertension.

PMID- 8886692
TI  - Diagnostic value of transvaginal color Doppler flow in ovarian torsion.
AB  - OBJECTIVE: To evaluate the role of Doppler flow in the diagnostic process of
      ovarian torsion. METHODS: Twenty-two patients who displayed the clinical symptoms
      of abdominal pain concomitant with an ovarian mass and were scheduled for
      explorative laparoscopy were enrolled in the study. The cohort was divided into 3
      groups: (A) 8 patients with clinical and sonographic evidence of torsion; (B) 8
      patients with abdominal pain and sonographic diagnosis of hemorrhagic cyst; and
      (C) 6 patients with a simple cystic mass who had undergone explorative surgery
      due to abdominal pain. RESULTS: After Doppler flow imaging, Group A displayed no
      blood flow within the mass, and surgery confirmed the diagnosis of ovarian
      torsion. Seven of the 8 group B patients showed ovarian vascular flow (RI = 0.472
      +/- 0.067). Only 2 of the 6 Group C patients displayed vascular flow (RI = 0.680
      +/- 0.129) within an untwisted cyst, confirmed by laparoscopy. CONCLUSIONS: The
      combination of Doppler flow imaging with the morphologic assessment improves the
      diagnostic accuracy of ovarian torsion.

PMID- 8886693
TI  - A computer based, temperature controlled bipolar electrocoagulation system.
AB  - OBJECTIVE: To reduce complications during electrocoagulation particularly injury
      of other organs, a computer based, temperature controlled bipolar coagulation
      system has been developed. Under this system temperature in the tissue is kept
      between 60 degrees C and 95 degrees C during coagulation. A real time graphic
      display provides the surgeon with an actual temperature at the tip of the forceps
      during coagulation. STUDY DESIGN: Rabbit uterine horns were coagulated at 90
      degrees C and were examined histologically and histochemically at 6 weeks after
      coagulation. RESULTS: Electrocoagulation at 90 degrees C induced a total loss of
      LDH activity in the tissue. Lumen of the uterus was completely occluded when
      examined 6 weeks later. CONCLUSION: This system with low temperature is
      sufficient for homogenous coagulation of the tissue.

PMID- 8886694
TI  - The role of Doppler sonography in assessment of malignant trophoblastic disease.
AB  - An observational study on the role of Doppler sonography in the assessment of
      patients with malignant trophoblastic disease was performed in an Oncology Unit
      of a University teaching hospital. A total of 32 consecutive patients referred
      for chemotherapy were recruited. Twenty-three non-pregnant and 18 women in the
      first trimester of pregnancy acted as controls. The patients were prospectively
      followed-up for 2 years. It was found that the uterine arterial resistance index
      and pulsatility index in patients who required chemotherapy were significantly
      lower when compared with the non-pregnant and pregnant controls; (Student t-test;
      P < 0.001 and P < 0.01, respectively). Stepwise regression analysis of beta-hCG
      titres on uterine artery resistance index showed significant correlation, after
      controlling for uterine volume (adjusted multiple R = 0.71, P < 0.00001). There
      were, however, no significant independent associations between the initial
      uterine artery resistance index and the need for chemotherapy, number of courses
      of chemotherapy required, duration required for the beta-hCG titre to return to
      normal, presence of metastatic disease, or the subsequent development of drug
      resistance or relapse. It was concluded that uterine arterial Doppler indices are
      significantly correlated with trophoblastic activity (beta-hCG titres) in
      malignant trophoblastic disease. However, their role in the prediction of
      subsequent tumour behaviour need to be assessed in larger series.

PMID- 8886695
TI  - Stress urinary incontinence, a new concept.
AB  - OBJECTIVE: A new concept is put forward to explain stress urinary incontinence
      (SUI). Urine continence depends on an intact strong internal sphincter and a
      reactive sympathetic activity. STUDY DESIGN: Thirty patients suffering from SUI
      were evaluated clinically and by urodynamic studies. During surgical repair of
      SUI, minute tissues were taken from the bladder neck and were examined
      microscopically after preparation and staining. Furthermore, examination of 15
      postmortem specimens was done. Also a clinical trial was done to demonstrate the
      effects of sympathomimetics and alpha-blockers on the internal sphincter.
      RESULTS: There is paucity and dispersion of collagenous and elastic tissues
      constituents of the internal sphincter in patients suffering SUI. alpha-Blockers
      lower the urethral pressure, while sympathomimetics increases it. CONCLUSION:
      Sudden increase of intravesical pressure overcomes a weak internal sphincter
      leading to leakage of urine. This initiates a reactive sympathetic quick response
      that increases the internal sphincter tone preventing further leakage.

PMID- 8886696
TI  - Sequential addition of low dose of medrogestone or medroxyprogesterone acetate to
      transdermal estradiol: a pilot study on their influence on the endometrium.
AB  - We evaluated bleeding pattern and endometrium following the administration of two
      of the most common types of progestogens used in hormone replacement therapy,
      medroxyprogesterone acetate (MPA) and medrogestone acetate. Twenty eight patients
      in spontaneous menopause were randomly allocated to two groups. Group 1 (n = 14)
      received 5 mg/day of of MPA and group 2 (n = 14) received 5 mg/day of
      medrogestone: both the progestogens were sequentially added for the last 12 days
      of a 21-day period of transdermal estradiol administration (50 micrograms per
      day). A 7-day treatment-free period completed the cycle. The study treatments
      were administered for 6 cycles. The endomtria were checked for their thickness by
      transvaginal ultrasound before starting treatment and at 6th treatment cycle
      (days 6-10 of the estrogen-only phase and during the period between days 8 and 12
      of the progestogen addition). Endometrial biopsies were performed before starting
      treatment only in the patients with a positive progesterone challenge test and in
      all the patients at the end of the study during the addition of the progestogen.
      The bleeding pattern was closely monitored. MPA is accompanied by a thick
      endometrium with full secretory transformation in all cases. On the contrary, the
      same dose of medrogestone induced a consistent decrease of estrogen primed
      endometrium with only 4 cases of full secretory transformation. Four medrogestone
      treated patients dropped out due to unscheduled bleeding. A low dose of
      medrogestone added to transdermal estradiol induced incomplete transformation of
      endometrium and oligo-amenorrhea more frequently than MPA, but it increased the
      chances of irregular bleeding. MPA fully transformed the endometrium: periods
      were thus heavier but regular. None of the patients in either group had
      endometrial hyperplasia.

PMID- 8886697
TI  - New methods of mathematical analysis for studies of intrauterine contraception.
AB  - The authors present two new procedures of mathematical analysis to evaluate the
      incidents which arise during the use of any contraceptive method. These two new
      approaches, which the authors call the Probability Index (PI) and the Weighted
      Average Index (WAI), are compared to those by Pearl and Tietze. Their conclusions
      are that the PI, although the best estimator of real probability, is not as
      functional as the WAI. The latter is not only much easier to calculate than PI,
      but also presents a greater correlation, prediction accuracy and discriminant
      power than the Pearl and Tietze indexes.

PMID- 8886698
TI  - Laparoscopically assisted vaginal hysterectomy for non-malignant disease of the
      uterus. Report on a personal series of 126 cases.
AB  - OBJECTIVE: A report is given of a series of 126 laparoscopically-assisted vaginal
      hysterectomies (LAVH) for benign lesions, carried out between September 1990 and
      December 1995. MATERIALS AND METHOD: The mean age of the patients was 50.3 years,
      and the main indications for hysterectomy were metrorrhagia (88). The main
      reasons why LAVH was chosen from among other hysterectomy techniques were a large
      uterus (55), associated ovarian surgery (45), and a difficult vaginal approach
      (35). The surgical technique always began with a laparoscopic stage followed by a
      vaginal stage. The laparoscopic stage generally finished at the lower part of the
      broad ligament. The vagina was opened and the uterine arteries were ligatured by
      a vaginal approach (116). Only 10 total laparoscopic hysterectomies were
      performed. RESULTS: The mean duration of the operation was 72 +/- 28 min, mean
      blood loss was 1.89 g/dl, and mean uterus weight was 224 g (maximum = 1093 g).
      Operative complications consisted of two bladder wounds and two switches to
      abdominal hysterectomy. Postoperative complications were urinary infections (17),
      hemorrhages needing second-look operations [2] and abscess of the vaginal section
      requiring evacuation [3]. CONCLUSION: LAVH should never be carried out instead of
      vaginal hysterectomy (VH), since VH is the best procedure when it is easy to
      perform. The authors use LAVH when VH is difficult or contraindicated (the aim
      being to avoid laparotomy) and actually carry out less than 5% of hysterectomies
      for benign lesions by laparotomy.

PMID- 8886699
TI  - Combined use of a long-acting gonadotropin-releasing hormone agonist and low-dose
      danazol in advanced stage endometriosis.
AB  - In this preliminary study, the safety and efficacy of a combined GnRHa and low
      dose danazol regimen was evaluated in patients with advanced stage endometriosis.
      Five patients with stage IV endometriosis were administered triptorelin 3.75 mg
      intramuscularly with monthly intervals in combination with oral danazol 100
      mg/day for 6 months. Laparoscopy was performed before and after therapy to assess
      the change in endometriotic lesions. During controls, patients were evaluated for
      the change in hormonal and biochemical parameters and the side effects of the
      treatment. In 4 patients with ovarian endometriomas, cysts were drained during
      initial laparoscopy. None of the endometriomas persisted after therapy. Total
      scores, according to the revised American Fertility Society classification of
      endometriosis were, 54.8 +/- 10.9 before treatment and decreased to 31.6 +/- 10.3
      (P < 0.05), whereas, endometriotic implants scores changed from an initial value
      of 22.8 +/- 12.1 to 1.2 +/- 1.1 (P < 0.05). No adverse effect was observed on
      lipid and liver metabolism. Estrogen deprivation symptoms and oily skin were the
      most prominent complaints and one patient had a weight gain of 6 kg. Based on
      these results we conclude that a combination of GnRHa and low dose danazol is an
      effective alternative treatment modality in the treatment of severe endometriosis
      without any serious side effect.

PMID- 8886700
TI  - The residual ovary syndrome: a 20-year experience.
AB  - OBJECTIVE: To address the controversy of ovarian preservation during a
      hysterectomy for benign indications by using our experience with residual ovary
      syndrome (ROS). STUDY DESIGN: Over a period of 20 years, 2561 hysterectomies
      (during which one or both ovaries were preserved) were performed at the Golda
      Medical Center, Israel. A retrospective, quasi, case-control analysis was
      undertaken. RESULTS: The incidence of ROS was 2.85%. While chronic pelvic pain
      was the principle indication for subsequent reexploration in 52 patients (71.3%),
      an asymptomatic pelvic mass noted during routine follow-up examination accounted
      for 24.6% of operations for ROS. The majority (75.4%) of patients underwent
      surgery during the first 10 years, while the highest incidence occurred within
      the first 5 years (46.6%). Furthermore, histological examination revealed
      functional cysts, benign neoplasm and ovarian carcinoma in 50.7%, 42.6% and 12.3%
      of the cases, respectively (in nine patients more than one pathology was
      observed). CONCLUSIONS: Since ROS was found to occur in 1/35 women who had
      undergone previous hysterectomies mainly due to physiologic ovarian function and
      benign cyst formation, but not malignancy, we believe that routine oophorectomy
      is justified in premenopausal women over 45 years of age. However, the final
      decision to perform elective oophorectomy at the time of hysterectomy for benign
      disease should be established on an individual basis, taking into consideration
      age, individual and family risk factors, the patient's preference and ability to
      ensure long-term compliance to exogenous hormone replacement therapy.

PMID- 8886701
TI  - Vulvar vestibulitis subjects undergoing surgical intervention: a descriptive
      analysis and histopathological correlates.
AB  - OBJECTIVE: We describe here a series of selected patients from an established
      vaginitis research clinic diagnosed with vulvovestibulitis (VV) who underwent
      surgical intervention for focal disease. Long-term results of surgical correction
      are reported and characteristic histopathology findings associated with vulvar
      vestibulitis are emphasized. STUDY DESIGN: A retrospective chart review was
      carried out to extract relevant clinical, histologic, and outcome data. Tissue
      blocks of resected specimens were re-examined for specific inflammatory response.
      RESULTS: Complete data and long-term follow up were available in 16 patients who
      underwent surgical intervention. All were cared for by the same practitioner
      (CM). The mean (+/- S.D.) age and gravidity on presentation were 26.9 +/- 5.3
      years and 0.9 +/- 1.5, respectively. All but one was caucasian, and 70% were
      nulliparous. Symptoms included entry dyspareunia (100%), discharge (70%), burning
      (66%), itching (20%) and other (30%). All patients had focal tenderness; other
      findings were erythema (50%), acetowhite staining (80%), edema (20%),
      micropapules (20%) and condyloma (10%). After diagnosis, initial duration of
      conservative management was 9.4 +/- 6.9 months (1-26 months). No patients
      received interferon therapy. Because of persistent symptoms the 16 subjects
      underwent targeted partial perineoplasties. Initial histopathology results
      revealed chronic inflammation, parakeratosis, hyperkeratosis, edema, koilocytosis
      and acanthosis. When tissue blocks were cut and stained with Giemsa, large
      numbers of mast cells were identified. Mean postoperative follow up was 42.0 +/-
      22.4 months (10-70 months). Follow up after surgery showed an overall improvement
      in 15/16 patients (93.8%). CONCLUSIONS: VV affects primarily white, nulliparous
      women. In the carefully selected subject, surgical intervention has a high
      success rate, even on long-term follow up. Although the exact etiology for this
      condition has yet to be elucidated, the presence of mast cells supports an
      association with other genitourinary inflammatory syndromes such as interstitial
      cystitis; and allows for speculation about a possible role played by mast cell
      activation in the etiology of VV.

PMID- 8886702
TI  - Gonadotropin-releasing hormone agonist therapy induces apoptosis in uterine
      leiomyoma.
AB  - OBJECTIVE: We examined uterine tissue samples obtained from premenopausal women
      with uterine leiomyoma treated with gonadotropin-releasing hormone agonist
      (GnRHa) to investigate the mechanism of the effects of GnRHa. STUDY DESIGN:
      Surgically resected myoma tissue obtained from 26 premenopausal patients with
      uterine leiomyoma treated with GnRHa, 20 premenopausal patients with uterine
      leiomyoma who did not receive GnRHa treatment, and 15 postmenopausal women with
      uterine leiomyoma were examined histologically. RESULTS: GnRHa treatment reduced
      the size of uterine leiomyomata and induced significant hyaline degeneration in
      tumor tissue. Le(Y)-antigen expression was detected in 18 (69.3%) of 26 GnRHa
      treated patients (P < 0.02) and in 12 (80.0%) of 15 postmenopausal women (P <
      0.05), but in only eight (40.0%) of the 20 premenopausal patients who did not
      receive GnRHa. Apoptotic cells, detected by the nick-end labeling method were
      observed in 14 patients (53.8%) in the GnRHa-treated group, 10 patients (50.0%)
      in the non-treated group, and 12 postmenopausal women (80.0%). CONCLUSION: Our
      findings suggest that induction of apoptosis may be a mechanism of the effect of
      GnRHa in leiomyoma.

PMID- 8886703
TI  - Cervical intraepithelial neoplasia in pregnant intravenous drug users infected
      with human immunodeficiency virus type 1.
AB  - OBJECTIVE: The purpose of this study was to evaluate the frequency and natural
      history of cervical intraepithelial neoplasia (CIN) during pregnancy in past or
      current intravenous drug users infected with human immunodeficiency virus type 1
      (HIV-1). STUDY DESIGN: We prospectively evaluated 48 pregnant HIV-1 seropositive
      patients and 38 HIV seronegative controls. All the subjects were current or past
      intravenous drug users. Follow-up visits were carried out each trimester of
      pregnancy and 8-12 weeks post-partum with Papanicolau smears, colposcopic
      examinations and, when necessary, colposcopically directed cervical biopsies.
      RESULTS: Thirteen of 48 HIV-seropositive women (27.1%) and three of 38 HIV
      seronegative controls (7.9%) (P = 0.027 by Fisher exact test) had biopsy-proven
      CIN at the beginning of pregnancy. High-grade CIN was detected in 10 cases
      (20.8%) and in two (5.3%) controls (P = 0.058 by Fisher exact test). None of the
      cervical squamous intraepithelial lesions progressed throughout pregnancy, in
      both cases and controls. Post-partum cold-knife cervical conization was performed
      on seven patients with CIN III and examination of the cone biopsy specimens
      demonstrated persistence of CIN III. CONCLUSIONS: HIV-infected intravenous drug
      users are at high risk of CIN during pregnancy, thus requiring adequate screening
      programs. Our preliminary data suggest that the progression rate of CIN during
      gestation is low in this high-risk group.

PMID- 8886704
TI  - Placental transfer and maternal and fetal hemodynamic effects of ketanserin in
      the pregnant ewe.
AB  - OBJECTIVE: To determine placental transfer of ketanserin and to assess the effect
      of serotonin-2 receptor blockade by ketanserin on serotonin- and phenylephrine
      induced vasoconstriction. STUDY DESIGN: Five chronically instrumented pregnant
      ewes at 120 days gestation were injected with 20 mg ketanserin i.v., and fetal
      and maternal arterial samples were obtained at predetermined intervals to assess
      placental transfer. Maternal and fetal responses of blood flows and pressures
      were determined after injected of serotonin (20 micrograms/kg) or phenylephrine
      (10 micrograms/kg) before and after ketanserin (0.75 mg/kg). RESULTS: In the ewe,
      ketanserin is transferred across the placenta and reaches measurable levels in
      the fetal lamb. Ketanserin blocks the maternal and fetal serotonin-induced rise
      in arterial pressure, but not the serotonin-induced reduction in uterine blood
      flow. CONCLUSION: In the pregnant ewe, the serotonin-induced rise in maternal and
      fetal blood pressure is effectively antagonized by ketanserin, whereas the
      serotonin-induced reduction in uterine blood flow is not.

PMID- 8886705
TI  - Age and reproductive status affect basal venous tone in the rat.
AB  - OBJECTIVE: Changes in venous tone alter vessel diameter and capacitance of veins.
      These alterations may be induced by the steroid hormonal milieu. Therefore, our
      question was whether venous tone differs between estrous cycle, pregnancy and old
      rats. STUDY DESIGN: Mesenteric veins from young, pregnant and old Sprague-Dawley
      rats were dissected and cannulated in a venograph system with a continous readout
      of pressure-dependent lumen diameter. RESULTS: During estrous cycle venous tone
      was increased in metestrous (P < 0.05), whereas it was decreased in all old rats
      (P < 0.05). There was higher venous tone in pregnant animals compared to controls
      (P < 0.05). CONCLUSIONS: Venous tone exhibits marked differences during rat
      estrous cycle. It is increased during pregnancy and decreased in old rats.

PMID- 8886706
TI  - Effects of progesterone and oxytocin on intracellular elemental composition of
      term human myometrium in vitro.
AB  - OBJECTIVE: To study the effects of progesterone and oxytocin on contractile
      activity related to the intracellular elemental composition of human pregnant
      myometrium. STUDY DESIGN: Myometrial strips were mounted in tissue baths and
      superfused with plain buffer, oxytocin or progesterone. Progesterone was
      initially added to the tissue bath or at the onset of spontaneous contraction of
      the strips. The myometrial contractile activities were recorded isometrically and
      the results were analyzed by a specific computer program. The effects of oxytocin
      and progesterone on the intracellular elemental composition were studied by X-ray
      microanalysis in an electron microscope. RESULTS: The contractile activity in
      terms of frequency and tonus of the muscle strips was increased by oxytocin and
      progesterone. This increase was more pronounced if progesterone was added to the
      bath at the start of the experiment. After 120 min of incubation with oxytocin
      and progesterone the total intracellular concentration of calcium was
      significantly higher (P < 0.0001 and P < 0.002, respectively) compared to buffer.
      CONCLUSIONS: (i) Oxytocin increases total intracellular calcium concentration
      concomitant with an increase in uterine contractile activity. (ii) Progesterone
      increases the myometrial tone and frequency of contractions, simultaneously with
      an increase in total intracellular calcium.

PMID- 8886707
TI  - Sacrospinous ligament fixation by palpation: variation of the Richter procedure.
AB  - OBJECTIVE: To present our method of sacro-spinous ligament fixation by palpation
      and compare it to the classical approach described by Richter. MATERIAL: In
      addition to the standard instruments needed for vaginal surgery, we use a
      Rasemond dissector, a small O'Shaugnessy dissector with smooth branches. We also
      use a Bengolea forceps and a monothread-nylon (Ethilon), decimal 4 suture loaded
      on a needle with a 30-mm curve. PATIENTS: Twenty patients underwent this
      procedure from 03/15/1978 to 05/19/1995. Their ages ranged from 46 to 86 years
      with a mean age of 64.7 years. METHOD: This was a retrospective study of the
      indications, results and complications associated with this technique. RESULTS:
      With an average follow-up of 7 years, we observed 90% success, 10% recurrences,
      and no complication directly attributable to this technique. This technique is
      valuable because of its effectiveness and simplicity. CONCLUSIONS: Sacrospinous
      fixation by palpation is more simple and provides the same results as the classic
      exposure technique. We describe the technique in this text. The efficacy of sacro
      spinous ligament fixation by palpation would be improved by its systematic and
      bilateral use. Its value must be confirmed by a controlled prospective study to
      confirm our impression that our technique carries fewer risks.

PMID- 8886708
TI  - Intra-uterine fetal death following maternal varicella infection.
AB  - The association of varicella and pregnancy is very rare since 90% of women of
      reproductive age are immune. In the literature, a fetal varicella syndrome has
      been described characterized by multiple congenital malformations. We report here
      a case of intrauterine fetal death following maternal varicella at 17 weeks
      amenorrhea, with virological proof of fetal contamination. Because of the rarity
      of this association and by the same token of the fetal contamination during
      maternal varicella, the management during pregnancy rests essentially on a valid
      ultrasonic surveillance.

PMID- 8886709
TI  - Fetal Candida infection associated with an intrauterine contraceptive device.
AB  - Fetal Candida infection is rarely described but is often associated with a
      retained intrauterine contraceptive device (IUCD). A case of abortion due to
      Candida infection in a patient wearing an IUCD is reported.

PMID- 8886710
TI  - Portal vein thrombosis concomitant with thrombophilia during pregnancy.
AB  - The experience with portal vein thrombosis, an uncommon cause of portal
      hypertension complicating pregnancy is currently too brief to form definite
      conclusions regarding the management. The coexistence of the manifestations of
      portal hypertension as hypersplenism and esophageal varices together with Protein
      C and S deficiencies during pregnancy presents a real dilemma for diagnosis and
      management. We report the clinical follow-up of a 24-year-old woman in whom
      Protein C was detected in her two subsequent pregnancies besides portal vein
      thrombosis and discuss the changing levels of these proteins during pregnancy.

PMID- 8886711
TI  - Spontaneous reseal of the fetal membranes in patients with high-leak PROM,
      confirmed by intra-amniotic injection of a dye (phenol-sulfonphthalein).
AB  - Two cases (27 and 23 weeks of gestation) diagnosed as high-leak PROM by an intra
      amniotic dye (PSP) injection method later proved negative on re-testing by the
      same method, and ended in spontaneous reseal of the membranes. The pregnancies in
      these cases extended to 36 and 40 weeks of gestation without any eventful signs
      of infection.

PMID- 8886712
TI  - Hyper-IgD syndrome and pregnancy.
AB  - In this report two cases of the coincidence of hyperimmunoglobulinemia D syndrome
      (HIDS) and pregnancy are described. HIDS is not associated with complications in
      pregnancy or disturbance in fetal outcome; the frequency of attacks diminishes
      during pregnancy; HIDS probably inherits via an autosomal recessive trait and is
      not transmitted to children of patients.

PMID- 8886713
TI  - Budd-Chiari syndrome complicating severe preeclampsia in a parturient with
      primary antiphospholipid syndrome.
AB  - A 27-year-old primipara with severe preeclampsia and primary antiphospholipid
      syndrome developed right upper quadrant pain, massive ascites, HELLP syndrome,
      and disseminated intravascular coagulation shortly following vaginal delivery.
      Computed tomography and color Doppler studies were compatible with complete
      thrombosis of the right hepatic veins, the Budd-Chiari syndrome. Anticoagulation
      was initiated, along with supportive measures, and the patient recovered
      completely. Imaging studies 6 months later were normal. This case demonstrates
      that nearly fatal forms of venous thrombosis may complicate preeclampsia in women
      with antiphospholipid syndrome; Doppler studies of the hepatic vein are of value
      in establishing the diagnosis.

PMID- 8886714
TI  - Combined systemic and intra-amniotic treatment of cervical pregnancy by
      methotrexate. A report of two cases.
AB  - Two cervical pregnancies were treated with systemic and local methotrexate.
      Neither involuted significantly but one was successfully removed vaginally after
      17 days of treatment. The other required hysterectomy.

PMID- 8886715
TI  - CT hepatic and splenic appearances with sarcoidosis.

PMID- 8886716
TI  - Effect of verapamil on portal and splanchnic hemodynamics in patients with
      advanced posthepatitic cirrhosis using duplex Doppler ultrasound.
AB  - PURPOSE: To assess the effect of verapamil (80 mg) oral administration on portal
      and splanchnic hemodynamics in patients with advanced posthepatitic cirrhosis
      using duplex Doppler ultrasound (US). METHODS: Fourteen patients with post
      hepatitic liver cirrhosis were included in the study. Duplex Doppler sonographic
      examinations were performed before, and 2-3 h after, 80 mg verapamil oral
      administration. Portal and splanchnic hemodynamics including vessel diameters
      (mm), mean flow velocities (cm/s), blood flows (ml/min), Doppler indices such as
      pulsatility and resistive indices (PI and RI), were investigated before and after
      verapamil administration. RESULTS: After verapamil administration; diameter of
      portal vein, splenic vein, and superior mesenteric artery (SMA) showed increase
      of 8%, 10%, and 7% (P < 0.05 to < 0.001), respectively. Increases of 20%, 38%,
      and 47% were found in blood flows (P < 0.05 to < 0.0001) with respect to the
      above vessels. Decreases of 17%, 10%, 11%, and 7% were found in SMA PI, SMA RI,
      splenic artery (SA) PI, and SA RI, respectively (P < 0.05 to < 0.0001).
      CONCLUSIONS: Verapamil appears to have splanchnic, portal, splenic,
      portocollateral and probably intrahepatic vasodilator effects in patients with
      advanced posthepatitic liver cirrhosis. Verapamil should be further investigated
      in the treatment of patients with advanced liver cirrhosis with prospective
      studies measuring portal and wedged hepatic pressure.

PMID- 8886717
TI  - Duodenal tuberculosis.

PMID- 8886718
TI  - Clostridium difficile, pseudomembranous enterocolitis: striking CT and
      sonographic features in a pediatric patient.

PMID- 8886719
TI  - Adenocarcinoma of the gastro-esophageal junction: CT for monitoring during
      neoadjuvant chemotherapy.
AB  - OBJECTIVE: A clinical study was performed to assess the diagnostic value of
      spiral CT for evaluation of response during neoadjuvant chemotherapy (CTx) in
      patients with adenocarcinoma of the gastro-esophageal-junction (GEJ). Results
      were compared to those of endoscopy. METHODS AND MATERIAL: Twenty-five patients
      with histologically proven adenocarcinoma of the GEJ scheduled to undergo
      neoadjuvant CTx were studied. Before CT examination, 1200 ml of a vanilla
      flavoured paraffin emulsion were applied orally to the fasting patients and 40 mg
      BuscopanR or 2 mg glucagon were injected i.v. for hypotonia. Iodine (100 ml) was
      injected automatically (3 ml/s) and the CT scan was started 10 s after complete
      administration of CM. For response evaluation to CTx, four standardized
      parameters were measured by two experienced, blinded radiologists. The results
      were categorized according to the WHO classification of 1981 and compared to
      those of endoscopy. RESULTS: In 24 of 25 patients endoscopic and computed
      tomographic response evaluation showed a close correlation (r = 0.96).
      CONCLUSION: Spiral CT with negative oral contrast agent is a suitable technique
      for monitoring of GEJ masses. In combination with standardized metric parameters
      it offers a quantitative response evaluation in patients with GEJ masses during
      neoadjuvant CTx.

PMID- 8886720
TI  - Gastric leiomyosarcoma in a child.
AB  - Gastric leiomyosarcoma is a rare tumor in pediatric patients. The histological
      differentiation between leiomyoma and leiomyosarcoma is difficult. Computed
      tomography may allow the presumptive diagnosis of leiomyosarcoma to be made
      preoperatively and the surgical treatment can be planned in advance. We report a
      case of gastric leiomyosarcoma in a 2-year old boy. Ultrasonography and computed
      tomography demonstrated an inhomogeneous mass with areas of tumor necrosis and
      calcifications in the left upper quadrant.

PMID- 8886721
TI  - Small bowel volvulus following ileal pouch-anal anastomosis: CT demonstration.
AB  - We report a case of acquired small bowel volvulus as a cause of late obstruction
      after ileal J-pouch anal anastomosis. Computed tomography (CT) demonstrated signs
      of strangulated, adhesive obstruction with radial disposition of the loops around
      the mesenteric root and abnormal position of the superior mesenteric artery and
      vein on the right side of the aorta. These features were due to the surgical
      manipulation and tension of the mesentery and its vessels during ileoanal
      anastomosis.

PMID- 8886722
TI  - Pancreaticopleural fistula: a case report.

PMID- 8886723
TI  - Peritoneal lithiasis and cliptomas following laparoscopic cholecystectomy.
AB  - A review was made of five patients with post-laparoscopic cholecystectomy
      peritoneal soiling with clips and/or stone. Three patients were symptomatic with
      recurrent abdominal pain or back pain. One of these had clips alone, one had
      clips and stone and the third had stones alone. The location of the stones in the
      pelvis and right iliac fossa created confusion in the diagnosis, simulating
      ureteric calculi and appendicitis, respectively. Surgical operation revealed
      granulomas around the stones. The consequences of peritoneal clips is not yet
      known. However, peritoneal lithiasis and potential complications should be
      considered as a differential of abdominal and pelvic calculi.

PMID- 8886724
TI  - Leucocyte scintigraphy or computed tomography for the febrile post-operative
      patient?
AB  - OBJECTIVE: The optimal initial investigation for the post-operative patient with
      suspected occult intra-abdominal sepsis is controversial, although the diagnostic
      accuracy of a variety of techniques is known. Our objective is to determine which
      investigation has the greatest positive effect on patient management. METHODS AND
      PATIENTS: We reviewed 67 consecutive post-operative patients investigated for
      suspected occult sepsis retrospectively and analysed the sequence of
      investigations required to achieve the diagnosis depending on the choice of
      initial investigation, and the interval between between initiating investigations
      and performing definitive percutaneous drainage. RESULTS: Forty patients had
      scintigraphy as the initial investigation and 21 of these went on to require CT.
      None of the 27 patients who had CT as the initial investigation required any
      other imaging (chi 2 = 20.6, P < 0.0001) and appropriate percutaneous drainage
      was offered immediately. Conversely, the average interval to drainage in those
      who had scintigraphy first was 3.1 days. Fourteen out of 20 patients (70%) who
      had scintigraphy as the initial investigation following recent surgery, and 7 of
      20 (35%) following old surgery, needed subsequent CT. None of the 20 and 7
      patients in the recent and old surgery groups respectively who had CT initially
      required further imaging. CONCLUSION: Our results suggest recommending CT as the
      initial investigation in the early post-operative period as this will reduce the
      total number of investigations required to achieve the diagnosis and the time to
      definitive drainage. In the late post-operative period, scintigraphy will resolve
      the majority of problems.

PMID- 8886725
TI  - Percutaneous catheter drainage of tuberculous and nontuberculous psoas abscesses.
AB  - OBJECTIVE: To assess the utility of percutaneous catheter drainage in the
      management of tuberculous and nontuberculous psoas abscesses associated without
      any bony involvement or with minimal bony lesions that could not cause vertebral
      instability. MATERIALS AND METHOD: Eleven patients with psoas, iliopsoas and
      pelvic abscesses were drained under computed tomography and ultrasonography
      guidance. RESULTS: There were 15 (10 tuberculous, 5 pyogenic) abscesses in 11
      patients. Six of the tuberculous abscesses and one of the pyogenic abscess were
      associated with vertebral involvement. Vertebral lesions were located in one or
      two vertebrae without causing any serious disturbance in the vertebral
      stabilization. In one case, the abscess was bilateral. Nine cases were drained
      under computed tomography guidance, while two cases were drained under both
      computed tomography and ultrasonography guidance. One session drainage was
      sufficient for abscess resolution in uniloculated cases. In the two of four
      multiloculated cases, catheter drainage was performed twice. Relapse of the
      abscess was found in only one patient. The mean abscess volume was 520 ml and
      mean drainage duration was 12 days. None of the cases required surgery.
      CONCLUSION: Percutaneous drainage, chemotherapy and additional external brace
      application with the cases associated with bony lesion may be used for treatment
      of tuberculous and nontuberculous unilocule and multiloculated abscesses.

PMID- 8886726
TI  - Retrorectal mesenteric cyst (non-pancreatic pseudocyst) in adult.

PMID- 8886727
TI  - Coexisting non-functioning pheochromocytoma and renal oncocytoma: a case report
      and review of the literature.
AB  - We report a case of an oncocytoma, coexisting with a non-functioning
      pheochromocytoma in a patient who was operated on for suspicion of a renal tumor
      with metastases to the ipsilateral adrenal gland. As oncocytoma is a relatively
      rare lesion of the kidney, estimated to account for approximately 3-5% of renal
      neoplasms, its coexistence with non-functioning pheochromocytoma, to the best of
      our knowledge, has not hitherto been described in the medical literature.

PMID- 8886729
TI  - Perception of detail and greyscale range in X-ray fluoroscopy images captured
      with a personal computer and frame-grabber.
AB  - OBJECTIVE: To assess the dynamic range of radiological images captured with a
      personal computer frame-grabbing system coupled to an X-ray fluoroscopy machine.
      METHODS: A 386DX-40 MHz, IBM compatible, computer with an SVGA monochrome
      graphics subsystem and a 387 co-processor, installed with a Screen Machine frame
      grabber and controlled by a program specially written was used. Various systems
      were examined and the observer's perceptions of the results assessed. RESULTS:
      The dynamic range available to an ordinary X-ray fluoroscopy system was found to
      be restricted to about 750 mV. Similar measurements showed that the dynamic range
      was always restricted to 3/4-1/2 of the full available signal because of a high
      value of the dark voltage of the TV camera's target on all seven systems
      measured. The dynamic range of the computer-frame grabber system was found to be
      significantly wider than the Image Intensifier-TV camera chain but, surprisingly,
      it was affected by the type of file format used for image storing on disk.
      Clinical images from a barium meal examination as well as CT images captured
      after optimisation of the frame-grabber were found to contain large quantities of
      noise in the first two least significant bit planes making them redundant and
      limiting the grey levels needed for image display to less than 64. This number
      was also less than the 80 grey levels that could be discriminated by the human
      eye on the computer monitor. CONCLUSIONS: It was concluded that 6 bit
      digitisation would have been sufficient for image capture. The advantages of the
      wider dynamic range of the frame-grabber and the processing capabilities of the
      computer were tested for the possibility of improving the perception of detail.
      However, the results were negative. The limiting spatial resolution measured with
      a variable density bar pattern at all magnifications was about 0.4 lp/mm lower
      from that measured directly on the fluoroscopic screen. A detail perception test
      had the same result. The perception success was significantly lower with the
      digital images at all but the highest of the exposure rates and despite the use
      of image processing filters.

PMID- 8886728
TI  - Doppler-duplex ultrasound in renal colic.
AB  - OBJECTIVE: To determine the role of intrarenal Doppler ultrasound (US) in
      patients with renal colic and to establish the usefulness of this diagnostic
      method. MATERIALS AND METHODS: In 121 patients with renal colic and 70 healthy
      individuals, 382 kidneys were examined with color duplex US. Mean intrarenal
      arterial resistive index (RI), and the difference of mean RIs (dRI) between both
      kidneys were determined. In 64 patients, RI and dRI were compared with urographic
      findings (time of delay pyelogram between both kidneys). RESULTS: In the 70
      healthy individuals, RI was 0.62 +/- 0.045 and dRI 0.018 +/- 0.01. In the 121
      patients with renal colic, RI (0.71 +/- 0.06) was significantly superior (P <
      0.001) with respect to the opposite kidney, with a dRI of 0.09 +/- 0.055. In a
      correlation performed in 64 patients with urographic findings among color doppler
      US, with a RI > or = 0.70 and/or dRI > or = 0.06 as an indicative value of
      obstruction, sensitivity and specificity were 91.8% for patients with delayed
      pyelogram (n = 37 patients), and 48.1% for patients with nondelayed pyelogram (n
      = 27 patients) with a specificity of 92.8% with respect to the group of normal
      patients. In the group of patients with delayed pyelogram, RI was significantly
      superior (P < 0.05) in patients with an evolution time greater than 24 hours, in
      patients with proximal ureteral obstruction and in patients who had signs of
      pyelonephritis. There were no significant differences in the group of patients
      with nondelayed pyelograms. CONCLUSION: Color Doppler US is useful to
      fundamentally evaluate the consequences of the obstruction on renal function.
      Other factors such as evolution time of the symptomology, obstruction level, or
      existence of pyelonephritis can alter the US-Doppler values.

PMID- 8886730
TI  - Simple and rapid production of radiographic slides or prints using a personal
      computer and a laser imager.
AB  - A simplified and rapid method for making radiographic slides or prints using a
      personal computer, a computer monitor adapter and a laser imager is described.
      When the divided monitor output of a personal computer is connected to a laser
      imager in the Radiology Department, radiographs and text on the personal computer
      can be printed out from the laser imager. By selecting slide size print format,
      12 slide-sized images can be printed on a film. In addition, by selecting other
      print formats various sized images can be printed on film, which then can be used
      as teaching files or as backlight display panels for scientific exhibits. This
      method can only produce gray-scale printouts, which are sufficient for
      radiological presentations. Any radiology department can utilize this system by
      simply installing a computer monitor adapter.

PMID- 8886731
TI  - An automated intelligent diagnostic system for the interpretation of umbilical
      artery Doppler velocimetry.
AB  - The objective is to develop an automated intelligent diagnostic system for the
      interpretation of umbilical artery velocity waveforms. An ultrasound instrument
      with pulsed-wave Doppler is connected to a microcomputer by means of a frame
      grabber. After data acquisition, umbilical Doppler velocimetry is handled as a
      pattern recognition (feature extraction and classification) and decision-making
      problem. Automated image processing (enhancement, smoothing/ thresholding and
      edge detection) and analysis are used for feature extraction. Six waveform
      indices obtained by feature extraction are used as input layer to vector
      quantization which classifies waveforms into six groups. A clinical decision is
      assigned to each group by the medical expert. Our system is trained by 278 and
      380 waveform images of 94 normal and 157 high risk pregnancies, respectively. The
      system was tested with 193 and 61 images of normal and risky pregnancies; it was
      demonstrated that sensitivity and specificity of the system are 54.1% and 80.3%,
      respectively.

PMID- 8886732
TI  - Treatment of lumbar disc herniation in the second decade of life.
AB  - Lumbar disc herniation is rare in patients under the age of 20 years. In the
      department of orthopaedic surgery of the University Hospital of Frankfurt, 33
      patients below the age of 20 with lumbar disc herniation were treated over a
      period of 10 years. Eighteen were managed conservatively and 15 surgically. The
      purpose of this study is to report on the long-term outcome of these patients and
      to compare the results of conservative and surgical treatment. We analysed
      information obtained from the medical records, and for the long-term follow-up we
      prepared a questionnaire. The questionnaire was composed of general questions
      about the patients' lifestyle and their ability to return to a normal life and
      activity after treatment, together with a request for them to score their pain
      level and remaining symptoms. We found that the longest duration of symptoms
      before diagnosis was 72 months, with a mean duration of 11.1 months. Low back
      pain and monoradicular sciatica were the main complaints, but findings of
      neurological deficits were rare. Lasegue's sign and tight hamstrings seemed to be
      strong diagnostic signs in this age group. On the day of discharge, 94% of
      patients reported excellent or good results. The outcomes after a mean follow-up
      period of 5.4 years were similar in both treatment groups. Almost all patients
      were able to attain a normal activity level and few reported restrictions on
      their daily life. Only 14% complained of permanent pain and 7% reported poor
      results regarding their activity capabilities. In conclusion, we believe that in
      all cases of lumbar disc herniation in the second decade of life, conservative
      treatment should be pursued as a mainstay of treatment. Only after a certain
      time, if conservative treatment is ineffective, should surgical treatment be
      considered.

PMID- 8886733
TI  - Lumbar disc herniation: social and demographic factors determining duration of
      disease.
AB  - The study was set up to show whether certain social and demographic
      characteristics play any significant role in determining the duration of disease
      in patients with lumbar disc herniation. The study included 171 consecutive
      patients operated upon for the first time for lumbar disc herniation over a 1
      year period. Records were made of each patient's age, sex, domicile (town, rural
      area), social group and employment status. For each patient, four dates were also
      recorded: onset of symptoms, referral to hospital, operation and recovery. On
      this basis six periods could be calculated. Statistical analysis was used to
      identify the relation between the social and demographic factors and the various
      time periods between the onset of symptoms and recovery. Being employed,
      especially in a higher social group, cuts down the period from onset of symptoms
      to recovery. This shortening in the total duration mainly takes place between
      onset of symptoms and referral to hospital. The influences of domicile, age and
      sex were of no statistical significance. The median of the total period from
      onset of symptoms to recovery was 224 days. Among patients operated upon for the
      first time for lumbar disc herniation, employment denoted faster referral to
      hospital and thus faster operation and recovery. Among those employed, the
      patients from higher social groups were referred quickest.

PMID- 8886734
TI  - Sense of coherence and outcome of low-back surgery: 5-year follow-up of 80
      patients.
AB  - Eighty adult patients, 33 men and 47 women, mean age 46 years (SD 11.8, range 19
      74 years), were evaluated 5 years after low-back surgery. The mean duration of
      symptoms before operation was 8.7 (SD 7.1) years. The purpose was to evaluate the
      5-year outcome of low-back surgery, to find the best predictors for the outcome,
      and to find out if a correlation exists between the patient's sense of coherence
      and the outcome of low-back surgery. The mean Oswestry pain index for the whole
      group of patients improved from 3.8 to 2.7 (P < 0.001). The greatest improvement
      in pain was found in the group aged 35-50 years. In those over 50 years old, pain
      improved significantly more in women than men. Regarding walking ability, the
      mean Oswestry gait index for the whole group improved from 3.0 to 1.9 (P <
      0.001), with men over 50 years old achieving the greatest improvement in their
      walking. The mean Oswestry total index for the whole group was 41% before
      surgery, reflecting severe disability, and 25% at follow-up, reflecting moderate
      disability (P < 0.001). There was no difference between the mean values for men
      and women. Patients who had undergone several previous operations fared less well
      in the Oswestry total index, though their improvement was still significant (P <
      0.05). The postoperative Oswestry total index values correlated significantly
      with the sense of coherence (SOC) scale values (r = -0.23, P < 0.05). In all
      patients, the Oswestry total index before the index operation is suggested to be
      a predictor of the final outcome. In multiple regression analysis, the number of
      previous operations and the preoperatively recorded Oswestry total index appeared
      to be the best predictors for outcome of low-back surgery. We also found that the
      SOC scale correlated significantly with the Oswestry total index and seems to
      provide a possible explanation of ability to cope with the disability and pain
      associated with low-back disorders.

PMID- 8886735
TI  - Can a pharmacological pain analysis be used in the assessment of chronic low back
      pain?
AB  - A battery of pharmacological tests was used to differentiate the pain in patients
      with chronic low back pain (CLBP) referred for pain diagnosis and assessment of
      whether surgery was indicated or not. Forty patients (mean age 39 years, range 22
      51 years) suffering from CLBP (mean pain duration 5.9 years, range 1-12 years)
      participated. Three pharmacological approaches were used: (1) intravenous
      infusion of morphine, (2) intravenous infusion of lidocaine and (3) a diagnostic
      epidural opioid blockade. The patients were tested in a single-blind, placebo
      controlled fashion. The pain was considered nociceptive if it decreased by 50% or
      more in response to both intravenous morphine and epidural fentanyl, but
      increased in response to intravenous naloxone. The pain was considered
      neuropathic if it decreased by 50% or more in response to both intravenous
      lidocaine and the epidural local anaesthetic. Patients who registered a pain
      decrease of 50% or more in response to saline were classified as placebo
      responders. Those who registered less than 50% pain decrease in all the tests
      were considered nonresponders. According to the results of the tests, 16 of the
      patients were classified as having nociceptive pain, 8 neuropathic pain, 2 were
      placebo responders, 10 non-responders and 4 were unclassified. The results
      support the idea that this battery of pharmacological tests can be used in the
      classification of CLBP patients into different pain categories. This approach may
      prove useful as a guide for further patient evaluation and as a basis for choice
      of a suitable treatment strategy.

PMID- 8886736
TI  - Surgery of intramedullary spinal cord tumors.
AB  - The diagnosis and management of intramedullary spinal cord tumors have been
      significantly influenced by new diagnostic and surgical tools such as MRI,
      ultrasonic aspiration, intraoperative ultrasound, and evoked potential
      monitoring. In this study we compared the surgical results of our earlier cases
      using conventional methods with more recent cases using these new methods. We
      report our experience based on 44 adult cases. Histologic diagnosis revealed
      ependymoma (20 cases), astrocytoma (15 cases), glioblastoma multiforme (1 case),
      and other histologic diagnoses (8 cases). We performed 20 gross total resections,
      19 partial resections, and 5 biopsies. The mean follow-up period was 25.8 months
      (3 months-10 years). Surgical results were improvement in 11 patients (25%),
      stabilization in 24 (54%), and deterioration in 9 (20%). The first 28 cases
      (group A) were diagnosed using conventional myelography and CT myelography. The
      more recent 16 cases (group B) were diagnosed with MRI and operated on using
      techniques such as ultrasonic aspiration, intraoperative monitoring and
      ultrasound imaging. Radical surgery (total excision) was performed in 36% (n =
      10) of group A, while it was possible in 62% (n = 10) of group B. Deterioration
      after operation was noted in 28% (n = 8) of group A, but only 6.2% (n = 1) of
      group B. These results stress the importance of a preoperative MRI scan and the
      positive effects of intraoperative ultrasound imaging, ultrasonic aspiration, and
      evoked potential monitoring on surgical results. With the help of these tools,
      most intramedullary spinal cord tumors may be diagnosed and treated surgically
      with significantly decreased risk. Radical surgery was possible in as many as 62%
      of our more recent patients. Partial resection with radiotherapy should be
      confined to patients with high-grade astrocytomas.

PMID- 8886737
TI  - The development of adolescent idiopathic scoliosis.
AB  - There are many conflicting actiological theories for adolescent idiopathic
      scoliosis. We present a simple new model of scoliosis and a mechanism by which it
      is initiated and progresses. This mechanism provides a final common pathway for
      the multiple aetiological factors. A simple model of the spine, incorporating its
      fundamental mechanical features, was constructed. The model consisted of
      interconnected anterior compression and posterior tension columns. It allowed
      normal spinal movements, with flexion limited by the posterior column and
      rotation centered around the anterior column. It also allowed deformities to
      develop. The ends of the model were fixed in the position of the vertebrae they
      represented. Overgrowth of the anterior column relative to the posterior column
      caused the model to take up the shape of an idiopathic scoliosis. The greater the
      overgrowth, the more marked the deformity. Normally anterior and posterior column
      growth are coupled. During the growth spurt the thoracic kyphosis flattens
      indicating that anterior growth temporarily exceeds posterior growth. If this
      over-growth is marked a scoliosis will develop, as demonstrated by the model.
      Once this occurs the coupling is lost, anterior growth further outstrips
      posterior growth and the deformity progresses. Not all scolioses worsen, as the
      tendency to progress is balanced by neuromuscular factors and remodelling.
      Factors that increase the growth rate, induce asymmetry or decrease the inherent
      stability of the spine all encourage the development and progression of a
      scoliosis. This explains the complex biomechanics of scoliosis and provides a
      final common pathway by which the multiple aetiological factors can induce
      idiopathic scoliosis. It has important implications for the understanding and
      treatment of this condition.

PMID- 8886738
TI  - Bone quality in the lumbar spine in high-performance athletes.
AB  - Little is known about the influence of high-performance training on the bone
      quality of the lumbar spine, in particular, the effects on bone mineral density
      (BMD) in athletes with high weight-bearing demands on the spine. Measurements
      were therefore performed in internationally top-ranked high-performance athletes
      of different disciplines (weight lifters, boxers, and endurance-cyclists). The
      measurements were carried out by dual-energy X-ray absorptiometry, and the
      results compared with the measurements of 21 age-matched male controls. The BMD
      of the high-performance weight lifters was greater than that of the controls by
      24% (0.252 g/cm2) on the AP view by 23% (0.200 g/cm2) on the lateral view (P <
      0.01), while difference in BMD between the boxers and the controls was +17%
      (0.174 g/cm2) on the AP view and +19% (0.174 g/cm2) on the lateral view. The BMD
      of the lumbar spine in all endurance cyclists was lower than that in the controls
      (AP view -10%, 0.105 g/cm2; lateral view -8%, 0.067 g/cm2; P > 0.05). The results
      show that training program stressing axial loads of the skeleton may lead to a
      significant increase of BMD in the lumbar spine of young individuals. Other
      authors' findings that the BMD of endurance athletes may decrease are confirmed.
      Nevertheless the 10% BMD loss of cyclists was surprisingly high.

PMID- 8886739
TI  - Spontaneous spinal epidural hematomas: is the role of dural arteriovenous
      malformations underestimated?
AB  - Two recent observations of spinal epidural hematomas (SEH) are presented: one of
      them was associated with iatrogenic coagulopathy, the other, apparently
      "spontaneous", required reoperation for early recurrence and was finally
      attributed to ruptured epidural arteriovenous malformation missed during the
      first procedure. Both patients underwent complete recovery. Although modern
      neuroimaging provides quick, noninvasive, and sensitive assessment of spinal
      epidural bleeding, we believe that preoperative spinal angiography is indicated
      in "spontaneous" SEH with subacute clinical course. Demonstration of underlying
      vascular anomaly would allow better surgical planning, complete obliteration of
      abnormal vessels, and prevention of recurrences. Essential epidemiological,
      pathogenetical, and clinical aspects of SEH are reviewed.

PMID- 8886741
TI  - Thoracic spinal cord compression caused by hypophosphataemic rickets: a case
      report and review of the world literature.
AB  - Vitamin D resistant hypophosphataemic rickets is a rare cause of spinal cord
      compression. The compression is caused by a combination of thickening of the
      laminae and calcification of the ligamentum flavum. Modern imaging techniques
      including CT and MRI provide excellent detail of both the level and degree of
      compression. MRI is particularly useful for examining the rest of the spinal cord
      for areas of impending compression and for postoperative follow-up. With careful
      surgical decompression a full neurological recovery can be achieved.

PMID- 8886740
TI  - Cervical spontaneous epidural hematoma as a complication of non-Hodgkin's
      lymphoma.
AB  - Epidural hematoma is a rare cause of spinal cord compression, which usually
      provokes severe neurological deficits. It is presumed to originate from venous
      or, more probably, arterial bleeding. Thrombocytopenia and other disorders of
      coagulation may precipitate the onset of epidural hematoma and facilitate the
      evolution of the disease. We report the case of a patient suffering from a non
      Hodgkin's lymphoma with severe thrombocytopenia during a MACOP-B schedule, who
      presented with a spontaneous cervical epidural hematoma. We discuss the
      etiopathological aspects, diagnosis, and treatment of this rare cause of acute
      cervical spinal cord compression.

PMID- 8886742
TI  - Bilateral traumatic abducens nerve paralysis with cervical spine flexion injury.
AB  - Bilateral traumatic abducens nerve palsy is a rare condition. We report a case
      associated with cervical spine flexion injury. This may be the first such case
      report, as no similar case was found in our review of the literature. The
      mechanisms of injury in this case are relevant to theories that explain
      hyperextension injuries.

PMID- 8886743
TI  - Simultaneous three-level disc herniation in a patient with multiple sclerosis.
AB  - A rare case is presented of symptomatic simultaneous multilevel disc herniation
      in the cervical, thoracic and lumbar spine of a 38-year-old man, which were
      operated on at three different timepoints. Following the third operation, the
      patient was diagnosed with multiple sclerosis, based on pathological visual
      evoked potentials and cerebrospinal fluid examination. Spinal surgeons should be
      aware of the uncommon simultaneous presence of symptomatic disc herniations at
      different spinal levels, and of the possibility that such multilevel disc
      herniations may coexist with demyelinating diseases and may confuse the
      diagnosis.

PMID- 8886744
TI  - Direct pediculo-body fixation in cases of spondylolisthesis with advanced
      intervertebral disc degeneration.
AB  - In inveterate cases of grade 2-3 spondylolisthesis (degenerative or
      spondylolytic), segmental mobility may be reduced by radiologically confirmed
      disc resorption. Fusion may be indicated in patients with persistent pain. A
      simple technique for fusion without reduction of the spondylolisthesis is
      presented. Fixation of the segment is achieved by two cancellous bone screws
      inserted bilaterally through the pedicles of the lower vertebra into the body of
      the upper slipped, vertebra. The cases of 16 patients with an average follow-up
      of 31 months (range 24-27 months) treated with this direct pediculo-body fixation
      are presented. Clinical evaluation showed significant decrease in pain and, in
      patients with concomitant spinal stenosis, walking distance without pain improved
      from between 500 and 1000 m to more than 3000 m. Radiologically, fusion was
      observed in all cases. The presented technique of internal fixation of a slipped
      segment in the degenerative lumbar spine represents a simple minimally traumatic
      procedure with successful clinical and radiological outcome. Additional
      procedures, such as decompression of the spinal canal, may be performed.

PMID- 8886745
TI  - Regulation of energy balance by leptin.
AB  - The high prevalence of obesity and its well documented association with the
      cardiovascular risk factors diabetes mellitus, dyslipidemia and hypertension
      represents a major problem for the general health status of industrialized
      societies. Although numerous studies have shown that genetic factors have a major
      influence on the regulation of energy homeostasis and the susceptibility to
      obesity, the genes and predisposing mutations involved are insufficiently
      understood. Among several known rodent models of obesity due to single gene
      mutations, mice homozygous for the obese (ob) gene exhibit massive early-onset
      obesity, hyperphagia, non-insulin-dependent diabetes mellitus, defective
      thermoregulation and infertility. Recently the ob gene was identified by
      positional cloning and shown to be mutated in ob/ob mice. Leptin, the product of
      the ob gene, is a 167-amino acid secreted protein that is synthesized exclusively
      in adipose tissue. With the exception of ob/ob mice, circulating plasma leptin is
      elevated in obesity. Administration of recombinant leptin to ob/ob mice reduces
      fat mass, food intake, hyperglycemia and hyperinsulinemia. The various effects of
      the hormone are mediated by leptin receptors expressed at high levels in the
      hypothalamus, but also in several other non-neuronal tissues. A mutation in the
      leptin receptor gene is responsible for the obese phenotype of db/db mice. Plasma
      leptin in humans is positively correlated with body fat mass, suggesting that
      leptin resistance rather than leptin deficiency is a common feature of human
      obesity. This review briefly summarizes the current status of the rapidly growing
      evidence that leptin plays an important role in the regulation of body weight and
      fat deposition.

PMID- 8886746
TI  - Decreasing sperm counts? A critical (re)view.

PMID- 8886747
TI  - Melatonin as antioxidant--use or misuse?

PMID- 8886748
TI  - A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy.
AB  - In a double-blind, randomized, controlled study, the effectiveness of treatment
      with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative
      of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective
      parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic
      patients with diabetic polyneuropathy. The results showed a significant
      improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a
      statistical trend toward improvement of the vibration perception threshold. Long
      term observation of 9 patients with verum over a period of 9 months support the
      results. Therapy-specific adverse effects were not seen. The results of this
      double-blind investigation, of the long-term observation and of the reports in
      the literature support the contention that the neurotropic benfotiamine-vitamin B
      combination represents a starting point in the treatment of diabetic
      polyneuropathy.

PMID- 8886749
TI  - Metabolic and endocrine effects of interleukin-1 in obese, diabetic Zucker fa/fa
      rats.
AB  - IL-1, a cytokine produced predominantly by cell from the macrophage lineage, can
      affect multiple neuroendocrine and metabolic functions. We report here effects of
      this cytokine in obese, diabetic Zucker fa/fa rats. These animals are modestly
      hyperglycemic, hyper-lipemic, and markedly hyperinsulinemic. Changes in the
      levels of glucose, lactate, triglycerides, free fatty acids, insulin, glucagon,
      and corticosterone were detected following a single intraperitoneal or
      intravenous injection of IL-1 into fa/fa rats. No comparable changes were
      observed following administration of insulin. In fa/fa rats, the diabetic status
      is particularly manifested by an abnormal glucose tolerance. Administration of a
      bolus injection of IL-1 normalized the response of diabetic fa/fa rats to a
      glucose load. These rats not only returned to their basal glucose levels quicker,
      but reached glucose concentrations in blood which were comparable to, or even
      lower than those of Fa/? rats. Although the mechanism underlying the effects of
      IL-1 in fa/fa rats are presently not clear, the results obtained suggest that
      this cytokine tends to normalize glucose homeostasis and stimulate fat
      mobilization in these animals.

PMID- 8886750
TI  - Growth hormone substitution in growth hormone-deficient adults: effects on
      collagen type I synthesis and skin thickness.
AB  - Growth hormone stimulates collagen type I synthesis. Collagen type I is a common
      matrix compound in a large number of connective tissues. The aim of our study was
      to prove whether a stimulation of collagen type I synthesis might be accompanied
      by a deposition of collagen type I in the skin (cutis). Twenty growth hormone
      deficient hypopituitary patients were included in a randomised, double-blind,
      placebo controlled, prospective, twelve-month study (eighteen patients assessable
      at the end of the study). The patients were treated with recombinant human growth
      hormone 0.25 U/kg/week subdivided in daily subcutaneous injections beginning with
      half the dosage during the first four weeks. During the first six months half of
      the patients were treated with placebo. PICP, the indicator of collagen type I
      synthesis, was increased after six months of therapy when compared to placebo.
      Skin thickness measured by ultrasound at the forearm and mechanically at the
      dorsum of the hand with strong compression of the skin both increased
      significantly following growth hormone substitution. Our data indicate that the
      stimulation of collagen type I synthesis by growth hormone substitution is
      followed by a deposition of collagen type I in the skin.

PMID- 8886751
TI  - The effect of repeated amphetamine and cocaine administration on adrenal, gonadal
      and thyroid hormone levels in the rat plasma.
AB  - Effects of acute and repeated administration of cocaine and amphetamine on
      adrenal, gonadal and thyroid plasma hormone levels were studied in male rats.
      Acute and repeated cocaine (15 mg/kg i.p. one dose, or once an hour for 3 hr for
      8 days) enhanced the corticosterone level at 45 min after administration.
      Amphetamine (5 mg/kg i.p. one dose, or twice daily for 14 days) elevated the
      level of corticosterone after 2 hr. Acute amphetamine increased the progesterone,
      testosterone and androstenedione plasma levels, whereas acute cocaine had no
      effect on those parameters. Repeated psycho-stimulants decreased the level of
      androgens. Neither acute nor repeated administration of psychostimulants had any
      significant effect on the level of the thyroid hormone T3. The T4 plasma level
      decreased following repeated amphetamine only. The above results indicate that
      repeated psychostimulants enhance the activity of the hypothalamo-pituitary
      adrenal (HPA) axis and lead to a decrease in the hypothalamo-pituitary-gonadal
      (HPG) axis activity. On the other hand, the hypothalamo-pituitary-thyroid (HPT)
      axis seems to be more resistant to the psychostimulant action.

PMID- 8886752
TI  - Mild resistance to thyroid hormone with a truncated thyroid hormone receptor
      beta.
AB  - Recent studies have revealed mutations in the thyroid hormone receptor beta (TR
      beta) gene as a cause of the most cases of the thyroid hormone resistance
      syndrome. We have identified a novel nonsense mutation in codon 449 in the 3' end
      of exon 10 in the TR beta gene in a 16-year-old male patient with generalized
      resistance to thyroid hormone who also had familial thyroxine binding globulin
      deficiency. Receptor protein generated from this gene is thought to be 13 amino
      acid deficient at carboxy-terminus. Resistance to thyroid hormone was mild at
      least when the patient was evaluated. The patient was eumetabolic in the presence
      of elevated plasma-free thyroid hormone levels, and both thyrotrope and
      peripheral tissues responded to triiodothyronine (T3) administration. This
      mildness of resistance is in contrast to severe resistance to thyroid hormone in
      two previously reported cases with truncated receptors in which 16 amino acids or
      11 amino acids were deficient at C-terminus. Thus, truncation of C-terminus of
      thyroid hormone receptor beta does not uniformly produce sever resistance.

PMID- 8886753
TI  - Relationships between IGF-I, cortisol, and osteocalcin in peripheral plasma of
      growing pigs.
AB  - Osteocalcin is a bone specific protein which is secreted by mature osteoblasts
      and is measurable in peripheral blood plasma. In growing female pigs (n = 6)
      osteocalcin was measured in daily blood samples between an age of 125 to 238 days
      and the values were compared to IGF-I and cortisol. Mean concentrations of
      osteocalcin were 158 +/- 2.7 ng/ml and the concentrations were significantly
      correlated to those of IGF-I (r = 0.12 p < or = 0.01 n = 581) and cortisol (r =
      0.13 p < or = 0.01 n = 503). Both hormones and less pronounced osteocalcin
      revealed a rhythm-like pattern with a period of 10-14 days. In addition, rhythm
      like variations with a period of about 5 weeks are visible. The highest
      correlation was found between IGF-I and cortisol both within the animals (r =
      0.28, n = 508, p < or = 0.001) and between the individuals (r = 0.94, n = 6, p <
      or = 0.01). Thus a dialog between IGF-I and cortisol may be assumed. A possible
      physiological role is discussed.

PMID- 8886754
TI  - Effect of temperature and pH on the magnitude of the free fraction of cortisol in
      serum.
AB  - Concomitant effects of temperature and pH on changes in the magnitude of the
      free, unbound fraction of cortisol in human serum were studied at temperatures
      and pH ranging from 36 to 39 degrees C and from 6.9 to 7.4, respectively. Free
      fraction increased with increasing temperature and decreasing pH, the two factors
      acting synergically: a rise in temperature from 36 to 39 degrees C caused an
      about 30% increase in the free fraction at pH = 7.4, and at pH 6.9--over 2.2
      fold. At highest temperature-acidity combination, i.e. at 39 degrees C, pH = 6.9,
      the free fraction was as much as 2.5-fold higher, relative to standard conditions
      (ph 7.4, 37 degrees C). This implies that in vivo the free, biologically active
      fraction of cortisol may increase due to e.g. hyperthermia and acidosis at a
      constant total concentration of this hormone.

PMID- 8886756
TI  - One-month exposure to inhaled endotoxin produces a dose-dependent increase in
      stored mucosubstances in rat intrapulmonary airways.
AB  - This study examined the production of stored mucosubtances in rats after repeated
      exposure to aerosolized endotoxin, a common contaminant of bioaerosols. Male
      Fischer 344 rats were exposed to aerosolized saline (sham control) or endotoxin
      (target concentrations of 0.05, 0.5, and 5.0 micrograms/m3) for 3 h/day, 5
      days/week for 4 weeks. Following the final exposure, the left lung of each animal
      was lavaged and the right lung and nasal cavity were fixed with buffered
      formalin. Morphometric examination of Alcian blue/Periodic acid Schiffs-stained
      (AB/PAS) lung sections demonstrated dose-dependent increases in stored
      intraepithelial mucosubstances in the intrapulmonary airways of endotoxin-exposed
      rats. Threefold and eightfold increases in stored mucosubstances were observed in
      generation 5 airways of animals exposed to 0.5 or 5.0 microgram/m3 endotoxin,
      respectively (p < .05). This mucous cell metaplasia in the intrapulmonary airways
      was not accompanied by evidence of lung inflammation or increased AB/PAS-staining
      high molecular weight material in lavage fluid. Furthermore, despite significant
      deposition of endotoxin aerosols (mass median aerodynamic diameter of 1.9
      microns) in the nasal cavity, no significant changes in stored mucosubstances
      were observed in the nasal septum. In animals repeatedly exposed to 5.0
      micrograms/m3 endotoxin and allowed to recover for 1 month, stored mucosubstances
      in the intrapulmonary airway were still more than fivefold greater than control
      values. Thus, in rats, repeated exposure to inhaled endotoxin produced a
      persistent mucous cell metaplasia only in the intrapulmonary airways.

PMID- 8886755
TI  - Lung epithelial cell (A549) interaction with unopsonized environmental
      particulates: quantitation of particle-specific binding and IL-8 production.
AB  - The A549 cell line was used to model in vitro the interaction of alveolar
      epithelium with environmental particulates. Confocal and electron microscopy
      demonstrated A549 binding and internalization of titanium dioxide (TiO2), iron
      oxide (Fe2O3), concentrated ambient air particulates (CAPs), and the fibrogenic
      particle alpha-quartz. Flow cytometry allowed quantitation of particle binding by
      measuring increased right angle light scatter (RAS) (TiO2) [40 micrograms/mL],
      Fe2O3 [100 micrograms/mL], alpha-quartz [200 micrograms/mL], or CAPs [40
      micrograms/mL] fold increase RAS: 8.1 +/- 0.9, 4.3 +/- 0.4, 2 +/- 0.1, 1.6 +/-
      0.1, respectively). With this quantitative assay, binding of particle was found
      to be calcium-dependent for TiO2 and Fe2O3 (% inhibition, 61.0 +/- 1.9, 40.0 +/-
      5.6, respectively), while alpha-quartz binding was calcium-independent. A panel
      of polyanionic ligands known to inhibit scavenger-type receptors was used to
      identify binding mechanisms for environmental particulates. Both heparin and
      polyinosinic acid (polyI), but not the control polyanion chondroitin sulfate,
      caused marked inhibition of particulate binding by A549 cells (e.g., TiO2 [40
      micrograms/mL] binding; polyI, heparin, and chondroitin sulfate: 73.8 +/- 3.5,
      75.5 +/- 6.0, 7.5 +/- 6.7% inhibition, respectively; mean +/- SE, n > or = 4),
      indicating that scavenger receptor(s), albeit those distinct from the heparin
      insensitive acetylated-LDL receptor, mediate particulate binding. The
      particulates ability to stimulate interleukin (IL-8) production in A549 cells was
      also tested. alpha-quartz, but not TiO2 or CAPs, caused a dose-dependent
      production of IL-8 (range 1-6 ng/mL), demonstrating a particle-specific spectrum
      of epithelial cell cytokine (IL-8) response. The results suggest that lung
      epithelial cell interaction with environmental particles is mediated by distinct
      receptors and can lead to particle dependent cytokine responses.

PMID- 8886757
TI  - E1A-induced immortalization of rat type II alveolar epithelial cells.
AB  - Using a retroviral vector expressing the adenoviral 12S E1A gene product the
      authors have immortalized rat type II alveolar epithelial cells. For a period of
      time, the immortalized cells retain many of the ultrastructural characteristics
      of type II cells in situ, including the presence of lamellar bodies. By 250 days
      in culture, however, neither lamellar bodies, SP-A, nor a phospholipid profile
      characteristic of surfactant were present. The cell bind the lectin Maclura
      pomifera and stably express cytokeratins and the E1A gene product. The cell line
      also has a diploid karyotype, exhibits contact inhibition of growth, and does not
      grow in soft agar. E1A-immortalized cell lines should prove useful as models for
      study of certain aspects of type II alveolar epithelial cell function.

PMID- 8886758
TI  - Eosinophilic lung inflammation in particulate-induced lung injury: technical
      consideration in isolating RNA for gene expression studies.
AB  - Particulate and other pollutant exposures are associated with lung injury and
      inflammation. The purpose of this study was to develop an approach by which
      intact RNA could be obtained from inflamed lung tissue from particulate-exposed
      animals in order to correlate injury with specific gene expression. Male Sprague
      Dawley (SD) and Fischer-344 (F-344) rats were intratracheally instilled with
      saline or residual oil fly ash (ROFA) particles, 8.3 mg/kg body weight in saline.
      At various time points following ROFA instillation, lungs were either lavaged or
      used for RNA isolation. ROFA exposure produced an increase in bronchoalveolar
      lavage fluid (BALF) neutrophils in both SD and F-344 rats. A time-dependent
      increase in eosinophils occurred only in SD rats but not in F-344 rats.
      Extraction of inflamed pulmonary tissue having a high influx of eosinophils for
      RNA using the conventional acid guanidinium thiocyanate phenol-chloroform (AGPC)
      procedure failed to provide undegraded RNA suitable for RT-PCR and Northern blot
      analysis of beta-actin mRNA expression. Mixing intact total RNA from saline
      control rat lungs with degraded RNA samples from inflamed lung yielded a gel
      profile of degraded RNA, indicating the presence of ribonuclease-like activity in
      the RNA extracted from lung tissues having eosinophil influx. Evidently, the
      conventional AGPC procedure failed to completely remove ribonuclease activity
      associated with ROFA-induced pulmonary eosinophil influx. This study reports a
      single-step modification to the AGPC extraction method that does not require
      additional reagents or additional precipitation steps for extracting undegraded
      RNA from nuclease-rich inflamed lung tissue. The aqueous layer resulting from
      mixing homogenate and chloroform is extracted a second time using an equal volume
      of AGPC buffer followed by addition of chloroform and centrifugation. The second
      aqueous phase is then treated as described in the conventional RNA extraction
      protocol. This simple and convenient modification does not require multiple
      precipitations of RNA and yields undegraded RNA from inflamed lung tissue with a
      slightly higher A260/A280 ratio without affecting overall RNA recovery. The
      results indicate that undegraded RNA could not be isolated using the routine AGPC
      based isolation technique from lung tissue containing eosinophils following ROFA
      exposure. The degraded RNA preparations were unsuitable for gene expression
      studies. However, undegraded RNA can be isolated from these tissues by modifying
      the original AGPC RNA extraction procedure, which is suitable for gene expression
      analysis using northern blot and RT-PCR techniques.

PMID- 8886759
TI  - Deposition and clearance in large and small airways in chronic bronchitis.
AB  - Tracheobronchial clearance was studied twice in 16 patients with chronic
      obstructive bronchitis after inhalation of 6 microns (aerodynamic diameter)
      monodisperse Teflon particles labeled with 111In. At one exposure the particles
      were inhaled at an extremely slow flow, 0.05 L/s; at the other they were inhaled
      at a normal flow, 0.5 L/s. Theoretical calculations and experimental data in
      healthy subjects indicate particle deposition mainly in the smallest ciliated
      airways using 0.05 L/s, i.e., in the bronchiolar region, and an enhanced
      deposition in larger airways using 0.5 L/s. Lung retention was measured at 0, 24,
      48 and 72 h. Clearance was significantly every 24 h for both exposures (p < .05).
      The fractions of retained particles were significantly larger for particles
      inhaled at 0.05 L/s compared to 0.5 L/s at all points of time (p < .001).
      Compared to healthy subjects, the retained fractions of deposited particles were
      larger in patients with bronchitis breathing at 0.05 L/s, but smaller with
      breathing at 0.5 L/s (p < .01). Significant relationships were found between lung
      retentions and airway resistance (Raw) at 0.5 L/s, r = -.68 (p < .01), but not at
      0.05 L/s, and between lung retention at 24 h and weight of expectorated sputum at
      0.05 L/s, r = -.50 (p < .05). There was, furthermore, an almost significant
      relationship between sputum volume and rate of tracheobronchial clearance between
      0 and 24 h (in percentage of the total amount cleared during 72 h) at 0.05 L/s, r
      = .42 (p = .05). The results indicate that in patients with chronic bronchitis
      overall clearance of particles in small airways is incomplete, as compared to
      larger airways. An increased amount of mucus, however, seemed to improve
      clearance of peripherally deposited particles, possibly by making cough more
      effective in small airways.

PMID- 8886760
TI  - Role of endotoxin in tumor necrosis factor alpha expression from alveolar
      macrophages treated with urban air particles.
AB  - The effects of urban air and diesel particles on inflammatory cytokine gene
      expression, tumor necrosis factor alpha (TNF-alpha) in particular, were studied
      in rat alveolar macrophages. TNF-alpha, interleukin (IL)-1, IL-6, cytokine
      induced neutrophil chemoattractant (CINC), and macrophage inflammatory protein
      (MIP)-2 gene expression and TNF-alpha secretion were increased in cells treated
      with 50 to 200 micrograms/mL of urban air particles in a concentration-related
      manner. There was no cytokine induction by diesel particles at any of the
      concentrations tested. Cytokine expression was not related to reactive oxygen
      species since antioxidants, such as catalase, TMTU, or DMSO, had no effect on TNF
      alpha secretion. However, cytokine induction by urban air particles was
      completely prevented by polymyxin B, an antibiotic capable of neutralizing
      bacterial lipopolysaccharide (LPS) activities. Furthermore, LPS was detected on
      the urban air particles, but not on diesel particle. These results suggest that
      activation of cytokine gene expression and secretion in rat alveolar macrophages
      by urban air particles is due to the presence of endotoxin on the particles.

PMID- 8886761
TI  - Impact of publicly funded contraceptive services on unintended pregnancies and
      implications for Medicaid expenditures.
AB  - Of U.S. women who use a reversible method of contraception, 24% each year obtain
      family planning services from a publicly funded clinic or a private doctor
      reimbursed by Medicaid. If these subsidized contraceptive services were not
      available, women who currently use them would have an estimated 1.3 million
      additional unplanned pregnancies annually, of which 29% would involve women aged
      15-19, 67% would involve never-married women and 61% would involve women with a
      household income below 200% of the federal poverty level. An estimated 632,300 of
      these pregnancies would end in induced abortion, an increase of 40% over the
      current national level. Another 533,800 pregnancies would result in unintended
      births. Some 76,400 of these would be births to families already receiving public
      assistance, and 64,100 would be to families that would become eligible for public
      assistance because of the birth; another 197,000 would be to women whose families
      would not receive public assistance, but would be eligible for Medicaid coverage
      of pregnancy, delivery and newborn care. In FY 1987, public-sector expenditures
      for contraceptive services totaled an estimated $412 million. If subsidized
      services had not been available, the federal and state governments would have
      spent an additional $1.2 billion through their Medicaid programs for expenses
      associated with unplanned births and abortions. Thus, for every dollar spent to
      provide publicly funded contraceptive services, an average of $3.00 was saved in
      Medical costs for pregnancy-related health care and medical care for newborns.

PMID- 8886762
TI  - Condom availability programs in U.S. schools.
AB  - School condom availability programs have been promoted as a promising approach
      for increasing condom use among students, for reducing the risk of infections
      with the human immunodeficiency virus and with other sexually transmitted
      diseases and for preventing unintended pregnancy. Data from a telephone survey of
      key individuals at school condom programs across the United States suggest that
      as of January 1995, at least 431 public schools in 50 U.S. school district made
      condoms available-2.2% of all public high schools and 0.3% of high school
      districts. In about half of the schools that were surveyed, students obtained
      more than one condom per student per year, on average, and in 14% students
      obtained more than six. Students in alternative schools, in smaller schools, in
      schools that made condoms available in baskets and in schools with health clinics
      obtained more condoms per student per year than did students in other schools.

PMID- 8886763
TI  - Private physicians' provision of contraceptive services.
AB  - Private physicians provide family planning services to the majority of American
      women. According to data from the National Ambulatory Medical Care Survey, office
      based physicians received on average 13.5 million visits annually for
      contraceptive services during 1990-1992. Private insurance was the expected from
      of payment for 38% of visits, while managed care covered 22% of visits, and
      Medicaid or another source of public assistance subsidized 12%; 22% were self
      paid and 6% covered by other sources. The majority of patients who received
      contraceptive services gave a reason other than general family planning or care
      regarding a specific contraceptive as the primary purpose for their visit,
      although women covered by a managed care plan or through public funding were the
      most likely to give general family planning needs as the main reason. Women whose
      visit was listed as publicly funded were less likely to have a contraceptive
      prescribed or provided or to obtain a Pap test than were those expected to pay
      with private insurance.

PMID- 8886764
TI  - The program archive on sexuality, health & adolescence: promising "prevention
      programs in a box".
AB  - The Program Archive on Sexuality, Health & Adolescence (PASHA) identifies
      programs aimed at preventing pregnancies and sexually transmitted diseases among
      teenagers, and makes materials from interventions with demonstrated effectiveness
      available to practitioners around the country. With the assistance of a panel of
      experts, PASHA has identified an initial group of 15 pregnancy prevention and 15
      sexually transmitted disease prevention programs for inclusion in its collection;
      to date, 24 programs have accepted PASHA's invitation to participate. Once a
      program agrees to participate, PASHA packages all materials required to replicate
      or adapt the intervention, along with a user's guide, two evaluation instruments
      and a directory guiding users to sources of assistance. As additional effective
      programs are identified and agree to submit their materials for archiving and
      distribution, they will be added to the collection.

PMID- 8886765
TI  - Men's perceptions of their roles and responsibilities regarding sex,
      contraception and childrearing.
AB  - Data from the 1991 National Survey of Men examine men's perceptions about their
      roles in relation to those of women in a couple's decision-making about sex,
      contraception and the rearing of children. A majority of men (61%) perceive that
      there is gender quality in sexual decision-making, and more than three-quarters
      (78%) believe that men and women share equal responsibility for decisions about
      contraception. However, men are three times as likely to say that women play a
      greater role in a couple's decisions about sex as they are to believe that men
      have the greater voice (30% compared with 9%). In contrast, men are more than
      twice as likely to perceive than men have a greater responsibility in
      contraceptive decisions as they are to say that women do (15% compared with 7%).
      Finally, 88% of men strongly agree that a man has the same responsibilities as a
      woman for the children they have together.

PMID- 8886767
TI  - Demographic and behavioral factors associated with adolescent pregnancy in
      Switzerland.
AB  - Switzerland has the lowest adolescent fertility rate in Western Europe. According
      to data collected in 1993 as part of the Swiss Multicentre Adolescent Survey on
      Health, 5% of 1,726 sexually active adolescents in a group of 3,993 15-20-year
      old women enrolled in academic or vocational classes had ever been pregnant; most
      of these women (80%) had terminated their pregnancy. Adolescents who had ever
      been pregnant did not differ significantly from those who had not by demographic
      characteristics. Multiple logistic regression analysis identified seven factors
      associated with pregnancy: having had four or more sexual partners; not having
      used contraceptives at first intercourse; ever use of less-effective
      contraceptive methods; having used illicit drugs during the last 30 days; living
      apart from one's parents; recently experiencing stress; and perceiving a lack of
      future prospects.

PMID- 8886766
TI  - A medical record linkage analysis of abortion underreporting.
AB  - Inaccuracy in women's reports of their abortion histories affects many areas of
      interest to reproductive health professionals and researchers. The identification
      of characteristics that affect the accuracy of reporting is essential for the
      improvement of data collection methods. A comparison of the medical records of
      104 American women aged 27-30 in 1990-1991 with their self-reported abortion
      histories revealed that 19% of these women failed to report one or more
      abortions. Results of logistic regression analysis indicate that nonwhite women
      were 3.3 times as likely as whites to underreport. With each additional year that
      had elapsed since the first recorded abortion, women became somewhat more likely
      to underreport (odds ratio of 1.3), while each additional year of a woman's
      education slightly decreased the likelihood of underreporting (odds ratio of
      0.7).

PMID- 8886768
TI  - Intrusiveness and closeness-caregiving: rethinking the concept of family
      "Enmeshment".
AB  - This article analyzes the concepts of "enmeshment" and "cohesion" and their
      entanglement in the field of family therapy. Early theories in this area were
      concerned primarily with processes of self/other differentiation. More recent
      theories have favored spatial metaphors that emphasize closeness-distance. We
      contend that self/ other differentiation and closeness-distance are different
      classes of behavior and that their linkage in the literature has obscured useful
      distinctions. Our analysis reveals two separate dimensions that clinicians and
      researchers should consider: Intrusiveness (including coercive control,
      separation anxiety, possessiveness/jealousy, emotional reactivity, and projective
      mystification); and Closeness-Caregiving (including warmth, time together,
      nurturance, physical intimacy, and consistency). We give definitions of these
      constructs and briefly examine their clinical and gender-related implications.

PMID- 8886769
TI  - Gender dilemmas and myth in the construction of marital bargains: issues for
      marital therapy.
AB  - Marital therapists are regularly confronted with issues of equality and fairness
      when working with couples. This article examines the social-contextual factors
      that influence couples' negotations about these issues. A common solution for
      couples, "the myth of equality," is identified, together with the processes that
      maintain it. The role of the therapist in relation to gender equality is
      addressed.

PMID- 8886770
TI  - Global Assessment of Relational Functioning scale (GARF): I. Background and
      rationale. Group for the Advancement of Psychiatry Committee on the Family.
AB  - The Committee on the Family of the Group for the Advancement of Psychiatry has
      introduced the Global Assessment of Relational Functioning (GARF), a scale that
      describes and quantifies the relational context within which patients live and
      problems occur. The GARF is intended to serve as a device that alerts clinicians
      to pay attention to the evaluation not only of individuals but also of relational
      functioning. In this article, we describe from a historicals perspective the
      scientific and political context within which this scale was developed. The GARF
      is analogous to Axis V of the DSM GAF scale (Global Assessment of Functioning)
      that is used to assess individual functioning. The GARF is a composite derivative
      of three major dimensionalized constructs, namely, joint problem solving,
      organization, and emotional climate. We provide five clinical vignettes to
      illustrate the process of arriving at GARF ratings. Finally, we discuss caveats
      and limitations for use of the GARF at present, and make recommendations for
      research projects and training methods that may enhance the value of this
      instrument in the future.

PMID- 8886771
TI  - Global assessment of relational functioning scale (GARF): II. Reliability and
      validity in a sample of families of bipolar patients.
AB  - The companion article by the Group for the Advancement of Psychiatry (GAP)
      Committee on the Family (see p. 155, this issue) describes the development of the
      Global Assessment of Relational Functioning (GARF) scale. The present study
      evaluated the reliability and concurrent validity of a manualized version of the
      GARF in recently episodic bipolar patients (N = 73) participating with family
      members in laboratory interaction tasks. The GARF was applied with high
      reliability by raters with little clinical experience. GARF ratings discriminated
      between families rated high and low in expressed emotion, with families rated as
      high in emotional overinvolvement showing the lowest relational functioning
      scores. GARF scores also correlated with affective negativity scores derived from
      the interactional task-based affective style and coping style coding systems.
      However, relational ratings were independent of levels of concurrent symptoms or
      illness chronicity among individual patients. GARF ratings may inform the
      treatment plans for patients with psychiatric disorders, but the optimal methods
      of data collection and rater training must be determined.

PMID- 8886772
TI  - Involvement, collaboration, and empowerment: a model for consultation with human
      service agencies and the development of family-oriented care.
AB  - Systems consultation to provider agencies can contribute considerably to the
      development of a collaborative, family-oriented approach in these agencies. The
      possibilities for such an undertaking depend on the establishment of working
      relationships at two interfaces: between the system consultant and the agency,
      and between the agency and its client families. A framework for developing these
      relationships in three sequential phases is proposed: involvement, collaboration,
      and empowerment (ICE). Each phase is characterized by a dominant issue that is
      processed at the time. It is possible for relationships to begin at a more
      advanced phase and to work through two or more phases simultaneously. However,
      premature attempts to do so, which often occur in agencies' work with involuntary
      clients and "difficult to engage" families, generate resistance and lead to an
      impasse. The applicability and usefulness of the ICE model is demonstrated by
      presenting the 6-year development of a family involvement and partnership program
      in Israel's juvenile correction system.

PMID- 8886773
TI  - Coping with stress in families of servicemen: searching for "win-win" solutions
      to a conflict between the family and the military organization.
AB  - The objective of this research was to explore the coping patterns of servicemen's
      families with the competing demands of two institutions: the military
      organization and the family. The sample comprised one hundred career soldiers
      along with their families. The research instruments included individual
      interviews, a battery of questionnaires, and a role-playing task. Examination of
      the couple's joint coping modes yielded two major categories of families-families
      that were successful in their efforts to resolve the military vs. family
      conflict, and families that did not manage to reconcile the competing demands of
      these two domains. Within each of these two categories there were a variety of
      distinct profiles. To compare the dynamics of successful coping with less
      successful coping regarding the military vs. family conflict, a conceptual model
      was suggested. This model subsumes the antecedent variables (job issues, support
      network, and couple relationships); mediating variables (cognitive appraisal of
      conflict severity and coping potential, as well as actual coping strategies); and
      outcome variables reflecting the degree of adjustment to the military vs. family
      conflict.

PMID- 8886774
TI  - Family values, religiosity, and emotional reactions to schizophrenia in Mexican
      and Anglo-American cultures.
AB  - This study was designed to test whether two sociocultural variables, family
      cohesion and religiosity, related to affective reactions toward schizophrenia. It
      was hypothesized that increasing perceptions of one's family as cohesive and
      religious would be associated with the expression of more favorable and less
      unfavorable emotions toward patients with the disorder. Eight-eight Anglo
      American undergraduates from Los Angeles and 88 Mexican undergraduates from
      Guadalajara read vignettes of a hypothetical family member described as meeting
      DSM-IV criteria for schizophrenia. Results of this study suggest that perceptions
      of family unity may be one important factor underlying emotional reactions toward
      schizophrenia. As expected, increasing perceptions of family cohesion were
      associated with greater reports of favorable emotion and decreased reports of
      unfavorable emotion toward the patient. However, after controlling for social
      desirability, family cohesion no longer significantly predicted unfavorable
      affect. Contrary to expectations, religiosity was not found to predict
      unfavorable or favorable emotions. However, religiosity was found to covary with
      nationality. Mexicans, compared to Anglos, reported greater moral-religious
      values in their families. No national differences were found with respect to
      family cohesion. Implications of this study are discussed along with suggested
      directions for future research.

PMID- 8886775
TI  - Translatability of family concepts into the Japanese culture: using the Family
      Environment Scale.
AB  - Family concepts and their measurements interest many family researchers. There is
      a question about the extent to which family concepts are universal or influenced
      by the culture in which the instrument originated. Using the Family Environment
      Scale (FES), the authors examine the translatability of family concepts into the
      Japanese culture. Forward- and back-translation processes and cross-cultural
      assessment of reliability and validity are discussed. We suggest that there may
      be different degrees of translatability for each of the family concepts used in
      the FES and that evaluation of families in different societies necessitates
      culturally appropriate constructs and instruments. The discussion is built around
      Japanese data, which are compared to the American results.

PMID- 8886777
TI  - Surgical treatment of recalcitrant plantar fasciitis.
AB  - Twenty-six patients (35 feet) underwent partial plantar fasciectomy with
      neurolysis of the nerve to the abductor digiti quinti muscle. Nonsurgical
      treatment for plantar fasciitis had been unsuccessful in these patients. Patients
      were followed after surgery for an average of 37.5 months. Six patients were male
      and 20 patients were female; the average age was 49 years. All patients had
      failed to respond to nonsurgical treatment for an average of 21.5 months. In
      addition to routine history and physical examination patients were evaluated
      before and after surgery with a subjective foot rating system, and a detailed
      questionnaire was used to assess post-operative functional outcome. Thirty-two
      patients (92%) had a satisfactory functional outcome, and three patients (8%) had
      an unsatisfactory result (21 excellent, 11 good, 3 fair, 0 poor). The Maryland
      Foot Score increased from a preoperative average of 74.8/100 points to a
      postoperative average of 90.6/100 points. Four patients (11%) had postoperative
      complications, including superficial wound infection (two patients), deep venous
      thrombosis (one patient), and superficial phlebitis (one patient), all of which
      resolved uneventfully with treatment. Ten patients (28.6%) reported some degree
      of heel pain after surgery. All 10 patients denied limitation in activity related
      to postoperative pain. The average period before return to daily activity and
      restricted work duty was 5.6 weeks and to full work duty without restriction was
      8.7 weeks. Although the length of time for partial or complete resolution of
      symptoms is variable, a successful treatment outcome can be expected in most
      patients who are treated for recalcitrant plantar fasciitis.

PMID- 8886778
TI  - Outcome of nonsurgical treatment for plantar fasciitis.
AB  - Four hundred eleven patients with a clinical diagnosis of plantar fasciitis were
      assessed for predisposing factors. Each patient completed an outcomes assessment
      survey instrument that ranked effectiveness of various nonsurgical treatment
      modalities. Listed in descending order of effectiveness, the treatment modalities
      assessed were short leg walking cast, steroid injection, rest, ice, runner's
      shoe, crepe-soled shoe, aspirin or nonsteroidal anti-inflammatory drug, heel
      cushion, low-profile plastic heel cup, heat, and Tuli's heel cup. Treatment with
      a cast ranked the best. The Tuli's heel cup ranked the poorest. Most of the
      treatments were found to be unpredictable or minimally effective. The
      ineffectiveness of nonsurgical treatments noted in this outcomes study is at
      variance with most published clinical studies in which generally favorable
      results are reported after nonsurgical treatment for plantar fasciitis.

PMID- 8886779
TI  - A comparison of MRI and clinical examination of acute lateral ankle sprains.
AB  - Because of its excellent soft tissue contrast and ability to demonstrate soft
      tissue structures, magnetic resonance imaging is ideally suited to the evaluation
      of the soft tissues surrounding the ankle, including the lateral collateral
      ligaments. This study was undertaken to compare the clinical evaluation of 15
      patients who suffered inversion injuries of the ankle with the results found on
      magnetic resonance imaging within 48 hours of the injury. Physical examination
      was found to be 100% accurate in the diagnosis of grade III ligament injuries but
      only 25% accurate in the diagnosis of grade II injuries. Clinicians most often
      underestimate the damage with a grade II ligament tear. Furthermore, other
      associated injuries, such as significant capsule ruptures and tendon damage, were
      often overlooked at physical examination.

PMID- 8886780
TI  - Control of the residual tibia in transtibial amputation.
AB  - Eight transtibial amputees had localized unremitting discomfort and pain in the
      distal anterior residual limb during prosthetic wear while weightbearing.
      Modification of the prosthetic socket did not change this pain. It was not
      consistent with "phantom limb" or causalgia/reflex sympathetic dystrophy-type
      etiologies. Thirteen randomly selected, pain-free, transtibial amputees were
      selected for comparison. The subjects in both groups used similar total-contact,
      "patellar tendon-bearing" prosthetic sockets fabricated and aligned with similar
      technique. The angles formed between the femur and tibia, femur and prosthetic
      socket, and tibia and socket were measured. Significant differences were found at
      each angle measurement between those patients who experienced pain and those who
      did not. The variable of tibia length had no effect. We conclude that bone
      alignment within the transtibial total-contact prosthetic socket may be partially
      dependent on surgical technique and not solely on prosthetic socket
      configuration.

PMID- 8886781
TI  - Talar neck fractures: anatomic considerations for posterior screw application.
AB  - The bony window available for posterior screw placement in the talus and the
      morphology of the talar neck were studied in 50 dry tali. In addition, 12 cadaver
      specimens were used to study the posterolateral approach. The bony window was
      bounded medially by the lateral tubercle of the posterior process of the talus,
      laterally by the fibular facet, superiorly by the trochlear articular surface,
      and inferiorly by the posterior calcaneal facet. The average vertical thickness
      at 2-mm increments was recorded across the talar neck to define the bony mass
      available for screw insertion. The smallest thickness of the talar neck was at a
      point 2 mm medial to the lateral border. The thickness progressively increased in
      a medial direction. The superior talar neck surface was found to have an average
      width of 18.4 +/- 1.6 mm. The angle formed between the superior and lateral
      surfaces of the talar neck averaged 29.3 degrees, which would account for the
      better delineation of the lateral border of the neck under fluoroscopy of the
      talus with the foot in pronation. The diameter of the screw in relation to the
      window height should be considered.

PMID- 8886782
TI  - Geometric data of hallux valgus feet.
AB  - The aim of this study is to find basic quantitative geometric data that may
      contribute to the understanding of the etiology of hallux valgus. Embalmed
      specimens with existing hallux valgus (N = 39) were dissected; 28 variables were
      measured with a Vernier caliper gauge and toe goniometer. Correlations between
      pairs of independent variables were calculated. Linear dependency of the hallux
      angle, varus angle, and the width of the forefoot on a number of independent
      variables was analyzed by multiple linear regression. A least squares method and
      a stepwise procedure were used. The distance from the tendon of the flexor
      hallucis longus muscle to the head of the first metatarsal bone explains more
      than other variables the variation in hallux angle and width of the forefoot. A
      widened forefoot is significantly correlated with both hallux and varus angles.
      The interrelation of the predictor parameters illustrates the complicated hallux
      valgus phenomenon.

PMID- 8886783
TI  - Ultrasound in the diagnosis of posterior tibial tendon pathology.
AB  - We retrospectively evaluated the effectiveness of ultrasonography as a diagnostic
      tool for investigating pathology in the posterior tibial tendon by comparing the
      preoperative ultrasonograms for 17 patients with their recorded surgical
      findings. In all cases, the surgical findings confirmed the ultrasonographic
      diagnoses: 3 inflammations, 4 partial tears, and 10 ruptures. Interestingly, two
      ruptures had been undiagnosed by magnetic resonance imaging. Ultrasonography,
      which seems to be a reliable means of visualizing the extent of pathology of the
      symptomatic posterior tibial tendon, may be a valuable tool in surgical planning.

PMID- 8886784
TI  - The role of internal fixation in the treatment of Jones fractures in diabetics.
AB  - The purpose of this study was to evaluate the treatment of fractures of the
      proximal fifth metatarsal at the junction of the metaphysis and diaphysis (i.e.,
      Jones fracture) in diabetics. Open reduction and internal fixation with bone
      grafting resulted in clinical and radiographic union 8 weeks after surgery in
      patients treated with either immediate or delayed open reduction and internal
      fixation. Open reduction and internal fixation with autologous bone grafting is
      an effective treatment regimen in the diabetic patient with a Jones fracture. An
      initial trial of casting can be attempted without any apparent deleterious
      effects on secondary open reduction and internal fixation.

PMID- 8886785
TI  - Calcaneocuboid joint involvement in calcaneal fractures.
AB  - The charts and radiographs of 48 surgically treated patients who underwent
      surgery for calcaneal fractures (right in 25 patients, left in 22, and bilateral
      in 1) between 1987 and 1994 were retrospectively reviewed. Coronal computed
      tomographic scans alone were obtained in 33 patients, and both coronal and axial
      computed tomographic scans were obtained in 9 patients. Three fractures exiting
      close to the calcaneocuboid joint (CCJ), but not involving the joint, were
      excluded. Nineteen patients (38.7%) had involvement of the CCJ. The extension of
      the fracture to the CCJ was apparent in anteroposterior or oblique radiographs or
      both in 18 patients. There was intra-articular fracture displacement of < or = 1
      mm in 6 patients, and 13 patients had a step or a gap of > or = 2 mm with or
      without angulation. Eleven patients had joint depression type fractures, 6 had
      tongue type fractures, and 2 had comminuted fractures. Extension of the calcaneal
      fracture into the CCJ was significantly more common with the joint depression
      type calcaneal fractures (chi-square test; P = 0.008). The coronal computed
      tomographic images showed significant lateral subluxation of posterior facet
      fragments in 8 patients and considerable comminution of the lateral calcaneal
      wall with or without lateral subluxation of posterior facet fragment in 10
      patients. These patients also had CCJ involvement, thus establishing a strong
      correlation between lateral subluxation of the posterior facet fragment or
      comminution of the lateral calcaneal wall and CCJ involvement. CCJ involvement is
      more common with joint depression type fractures. Extension of the fracture line
      into the CCJ should be suspected in presence of significant lateral column
      comminution or lateral talar subluxation.

PMID- 8886786
TI  - Peroneal tendon bupivacaine injection: utility of concomitant injection of
      contrast material.
AB  - Twenty patients received the installation of contrast material into the peroneal
      tendons while local anesthetic was injected as a diagnostic test. In three
      patients (15%), communication with the ankle joint and subtalar joint was noted,
      as well as failure of the contrast to fill the distal tendon. Injection of local
      anesthetic into the peroneal tendons as a diagnostic measure, therefore, may not
      have 100% sensitivity of specificity. Simultaneous injection of contrast material
      can be used to alert the clinician to a lack of specificity of the anesthetic
      test injection.

PMID- 8886787
TI  - Success of calcaneonavicular coalition resection in the adult population.
AB  - Twelve adult patients (13 feet), average age 33 years (range, 19-48 years), with
      calcaneonavicular coalitions remained symptomatic after a trial of conservative
      treatment. Surgical resections were performed. Before surgery, there was < 5
      degrees of inversion/eversion in 11 patients, radiographic evidence of
      degenerative arthritis in 10 feet (77%), and talar beaking in 7 feet. At an
      average postoperative follow-up of 36 months, subjective relief of preoperative
      symptoms was achieved in all but two patients. Two patients required subsequent
      hindfoot arthrodesis. Resection of calcaneonavicular coalition in the adult can
      be successful and provides an option to arthrodesis after nonoperative methods
      have failed.

PMID- 8886788
TI  - Clinical safety and efficacy of calf tourniquets.
AB  - A clinical study was undertaken to ascertain the utility and complication rate of
      proximal calf tourniquet use for foot and ankle surgery. The surgical and
      clinical records of 446 patients undergoing foot and ankle surgery between March
      1992 and December 1994 were examined for details pertaining to intraoperative
      tourniquet use and postoperative evidence of neurologic or vascular
      complications. All patients who had surgery performed under tourniquet control
      were included in the study. A total of 454 limbs were operated on: 8 patients
      underwent bilateral surgical procedures. The patients comprised 172 men and 274
      women. The average age was 48.9 (+/-16.0 SD) years. Surgery was completed in one
      tourniquet period in 435 cases (95.8%) and in two periods of tourniquet inflation
      in 19 cases (4.2%). The average duration of tourniquet ischemia was 49.2 minutes
      (+/-30.7 SD) for one tourniquet period and 131.1 minutes (+/-46.0 SD) for two
      tourniquet periods. No postoperative compromise to either neurologic or vascular
      function was detected. Specifically, no alteration in peroneal nerve function was
      seen. We conclude that a calf tourniquet placed proximally with adequate cast
      padding is a safe and effective method to achieve a bloodless surgical field for
      foot and ankle surgery.

PMID- 8886789
TI  - Plantarflexion injury to the metatarsophalangeal joint ("sand toe").
AB  - This is a retrospective study of 12 cases of hyperplantarflexion injuries to the
      great toe and the lesser toes sustained in professional beach volleyball players.
      The hyperplantarflexion injury to the metatarsophalangeal joint, referred to as
      "sand toe," can result in significant functional disability. Push-off, forward
      drive, running, and jumping are compromised. The average player in this series
      took 6 months to fully recover from the injury, and the most common problem after
      injury was the loss of dorsiflexion, seen in six players. Five players had
      residual discomfort in the injured toe, and two demonstrated an unstable toe.
      Individuals who experience sand toe injuries should be treated conservatively,
      with taping, anti-inflammatory medications, shoe wear modification, ice, and
      rest. A toe strengthening program is also presented.

PMID- 8886790
TI  - Clinical results of simultaneous adjacent interdigital neurectomy in the foot.

PMID- 8886791
TI  - Effect of vitamin E on human glutathione peroxidase (GSH-PX1) expression in
      cardiomyocytes.
AB  - To determine the effect of vitamin E on cellular antioxidant enzymes, human
      ventricular cardiomyocytes were incubated with 200 microM all-racemic-alpha
      tocopheryl acetate for 14 d at pO2s of 150 and 40 mm Hg. Cellular Cu, Zn
      superoxide dismutase, catalase, and GSH-Px1 activities were measured. Although
      SOD and catalase activities were unaffected by alpha-tocopherol, GSH-Px1
      activities increased (p < .0001) as much as twofold. This increase was
      independent of oxygen tension and selenium. The increase in GSH-Px1 activity
      became significant (p < .01) by day 4. A nonantioxidant analog of alpha
      tocopherol, 200 microM RRR-alpha-tocopherol methyl ether, did not affect GSH-Px1
      activities. Although GSH-Px1 mRNA levels mirrored the changes in enzyme
      activities, the de novo nuclear GSH-Px1 transcript synthesis was unaffected by
      alpha-tocopherol. Because the increase in GSH-Px1 activities also occurred after
      cellular alpha-tocopherol levels had plateaued, the above results were most
      consistent with posttranscriptional stabilization of GSH-Px1 mRNA by alpha
      tocopherol or an alpha-tocopherol-related metabolic product.

PMID- 8886792
TI  - Blood chemistry changes in the rat induced by high doses of nitronyl free radical
      spin traps.
AB  - For greatest efficacy, it is desirable to use spin trapping agents in the highest
      concentrations possible. Fifty-four male Sprague-Dawley rats were used to explore
      the relative toxicity of four representative nitronyl spin traps at doses chosen
      on the basis of earlier lethality studies. Most studies were confined to the 3-
      to 6-h period following drug injection, because the behavioral signs of toxicity
      are most evident early after injection and because spin trapping studies would
      typically be performed within this time frame. Doses of spin trap were dissolved
      in a corn oil/buffer vehicle and injected intraperitoneally (i.p.). Toxic signs
      were recorded periodically, and at the time of euthanasia or spontaneous death a
      blood sample was collected by cardiac puncture for clinical chemistry analysis
      and a necropsy was performed. Both gross pathology and histopathological
      examination of the major organs were essentially negative in all cases, with no
      obvious evidence of cellular damage being observed. Neither DMPO (232 mg/100 g
      b.wt.) nor PBN (100 mg/100 g b.wt.) were lethal in the present study, while both
      M4PO (20 and 40 mg/ 100 g b.wt.) and PyOBN (100 and 200 mg/100 g b.wt.) were
      lethal. Abnormal clinical chemistry findings were generally confined to those
      animals that died spontaneously or were euthanized early for humane reasons. In
      most cases, death was associated with marked seizure activity and impaired
      respiration, and deaths occurred within a few min to a few hours. The mechanism
      of toxicity was unclear due to the lack of histopathological evidence and the
      wide range of abnormal serum analytes in those rats killed by either M4PO or
      PyOBN. In conclusion, during the first 6 h after IP administration there is
      little indication of tissue damage by the nitrone spin traps until the dose is
      increased to a lethal level, at which point an acute, rapidly occurring, wide
      spread disruption of tissue integrity seems to occur.

PMID- 8886793
TI  - Induction of c-jun protooncogene expression by hydrogen peroxide through hydroxyl
      radical generation and p60SRC tyrosine kinase activation.
AB  - The mechanisms of signal transduction of c-jun induction by hydrogen peroxide are
      elucidated in NIH3T3 cells by using trapping agents of hydroxyl free radical or
      inhibitors of various protein kinases. Pre-treatment of the cell with hydroxyl
      radical scavenger dimethyl sulfoxide (DMSO) abolishes the H2O2-induced c-jun
      expression. Hydroxyl radical generation can be detected and quantified in cells
      treated sequentially with DMSO and H2O2 for 30 min respectively by methane
      sulfinic acid (MSA) production, especially that from particulate fraction.
      Induction of c-jun by H2O2 is also dramatically reduced by pretreating the cells
      with biological antioxidant vit. E. Protein tyrosine kinase activity of membrane
      fraction is induced by H2O2 within 5 to 10 min, which can be prevented by DMSO
      pre-treatment. Inhibitor of non-receptor type tyrosine kinase, herbimycin A, has
      inhibitory effect on H2O2-induced c-jun expression while the inhibitor of
      receptor type tyrosine kinase, tyrphostin 23 or inhibitor of cyclic AMP dependent
      protein kinase, KT 5720, has not. TPA pre-treatment that depletes protein kinase
      C (PKC) has no influence on the c-jun induction by H2O2. Our results suggest that
      the highly reactive species HO is generated after H2O2 enter cells and mediate
      the signal responses of H2O2 including c-jun induction and the activation of
      p60src tyrosine kinase might be one of the molecular events associated with the c
      jun induction pathway.

PMID- 8886794
TI  - Effects of neopterin-derivatives on H2O2-induced luminol chemiluminescence:
      mechanistic aspects.
AB  - Neopterin, 6-D-erythro-1',2',3'-trihydroxypropyl-pterin, and its dihydroform, 7,8
      dihydro-neopterin, are synthesized by human monocytes/macrophages upon
      stimulation by interferon-gamma. In the presence of iron chelator complexes
      neopterin enhances hydrogen peroxide-induced luminol chemiluminescence at neutral
      or slightly alkaline pH (7.5). In contrast, 7,8-dihydroneopterin scavenges
      chemiluminescence independently from the pH value and iron. In this study, we
      explored in more detail the mechanism possibly involved: analysis of the reaction
      products shows that 7,8-dihydroneopterin is oxidized and degraded to 7,8
      dihydroxanthopterin and xanthopterin, whereas the neopterin molecule is not
      chemically altered during the chemiluminescence reaction. Investigations of the
      neopterin-induced effect show that mannitol, a scavenger of hydroxyl radicals,
      does not alter the enhancing effect of neopterin. L-histidine, which scavenges
      singlet oxygen almost as effective as hydroxyl radicals, reduces the enhancing
      effect of neopterin. However, singlet oxygen was not detectable during the
      reaction by measuring monomol light emission (1270 nm). When replacing hydrogen
      peroxide by 3-morpholinosydnonimine, a generator of hydroxyl radicals, or
      naphthalene-endoperoxide, a generator of singlet oxygen, in the luminol
      chemiluminescence assay, neopterin shows no enhancing effect irrespective of the
      presence of iron-(III)-EDTA. The data suggest that neopterin enhances hydrogen
      peroxide-induced luminol chemiluminescence in the presence of iron-(III)-EDTA by
      formation of a catalytic complex that seems to favor the formation of oxygen
      intermediates which derive from hydrogen peroxide and react with luminol.

PMID- 8886795
TI  - Glutathione consumption and glutathione peroxidase inactivation in fibroblast
      cell lines by 4-hydroxy-2-nonenal.
AB  - Treatment of cultured fibroblasts, designated HA1 cells, with 4-hydroxy-2-nonenal
      (4HNE) in doses up to 50 nmol/10(6) cells for 3 h results in dose-dependent
      cytotoxicity measured by clonogenic cell survival with 50% cytotoxicity achieved
      at 32 nmol 4HNE/10(6) cells. 4HNE treatment also resulted in dose-dependent
      reduction of cellular glutathione (GSH) content and loss of glutathione
      peroxidase (GPx) activity at 4HNE doses greater than 15 nmol/10(6) cells. By
      comparison, a 95% oxygen-resistant variant of HA1 cells, designated O2R95 cells,
      and a hydrogen peroxide-resistant variant of HA1 cells, designated OC14 cells,
      were found resistant to 4HNE cytotoxicity requiring 54 nmol 4HNE/10(6) cells and
      75 nmol 4HNE/10(6) cells, respectively, for 50% cytotoxicity. In O2R95 cells,
      dose-dependent decreases were seen in GSH levels and GPx activity. In OC14 cells,
      however, any reduction in cellular GSH levels required doses of 4HNE greater than
      30 nmol/10(6) cells, and GPx activity remained unchanged. No changes were seen in
      glutathione-S-transferase activity in any of the cell lines at any dose tested.
      These data indicate a correlation between glutathione modification, in a manner
      that prevents its recycling, the ability to inactivate enzymes with active site
      selenocysteine residues and the cytotoxicity of alpha, beta-unsaturated aldehydes
      such as 4HNE.

PMID- 8886796
TI  - Protective effect of the nitroxide tempol against the cardiotoxicity of
      adriamycin.
AB  - Nitroxides are cell permeable, stable radicals that have been shown to exert
      antioxidant effects in several experimental models. In the present study, the
      ability of the piperidine nitroxide TEMPOL to prevent the acute cardiac toxicity
      of Adriamycin (ADR), which depends on oxygen-derived free radical generation, was
      assessed in isolated rat hearts. The results obtained show that TEMPOL (2.5 mM)
      significantly reduces the contractile impairment as well as the lipid
      peroxidation observed in rat heart preparations perfused with 100 micrograms/ml
      of ADR for 60 min. Both direct interaction with free radicals and decrease of
      Fe(II) availability (by stable oxidation and/or by chelation) seem to contribute
      to the cardioprotective effect to TEMPOL. HPLC and EPR studies of the subcellular
      distribution of TEMPOL indicate that substantial amounts of the nitroxide
      localize to the mitochondrial and microsomal fractions, in an ordered environment
      possibly corresponding to the interface between membrane and aqueous
      compartments.

PMID- 8886797
TI  - Accessibility and reactivity of ascorbate 6-palmitate bound to erythrocyte
      membranes.
AB  - Lipophilic derivatives of ascorbic acid may protect lipid bilayers and micelles
      against lipid peroxidation. In this work the binding, accessibility, and reducing
      capacity of ascorbate 6-palmitate (A6P) were studied in human erythrocyte
      membranes. In contrast to less lipophilic carbon-6-modified ascorbate
      derivatives, A6P bound to erythrocyte membranes in a concentration-dependent
      manner. This binding was preserved following centrifugation washes, but was
      largely reversed by extraction with bovine serum albumin. Most of the ascorbyl
      groups of membrane-bound A6P were readily accessible to oxidation by water
      soluble oxidants. Ferricyanide quantitatively oxidized membrane-bound A6P, but
      the latter spared endogenous tocopherols from destruction. In EPR studies, A6P
      was much more effective than ascorbate in reducing nitroxide spin labels
      positioned at either carbon-5 or carbon-16 of membrane-bound stearic acid in both
      intact cells and in membranes. A6P, thus, appears to intercalate into the
      erythrocyte membrane with the ascorbyl group located superficially, but with
      access to the hydrophobic membrane interior, and with the ability to recycle
      endogenous alpha-tocopherol during oxidant stress.

PMID- 8886798
TI  - Cyclic AMP-induced differentiation increases the synthesis of extracellular
      superoxide dismutase in rat C6 glioma.
AB  - The effect of membrane permeable cAMP analogues on the expression of
      extracellular superoxide dismutase (EC-SOD) was studied in rat C6 glioma. EC-SOD
      is constitutively expressed but stimulation with cAMP analogues still increased
      the EC-SOD transcription and the secreted SOD activity. The potency to enhance EC
      SOD expression is correlated with the ability of the cAMP analogue to induce cAMP
      dependent differentiation in C6. The increase in EC-SOD mRNA and in secreted
      activity depended on the concentration of the cAMP analogues and on the
      cultivation time. Twenty-four hours after addition of 0.5 mM N6, O'2-dibutyryl
      cAMP (dbcAMP) or N6-monobutyryl cAMP (N6-mbcAMP) EC-SOD mRNA expression increased
      approximately twofold, while stimulation for 68 h with 0.5 mM N6-mbcAMP or 1 mM 8
      Chloro cAMP (ClcAMP) and 1 mM dbcAMP enhanced the mean secreted activity/cell
      three- and fivefold, respectively. O'2-monobutyryl cAMP (O'2-mbcAMP) did not
      affect EC-SOD synthesis. The enhancement in EC-SOD activity did not require
      activation of protein kinase A. ATP, TGF-beta, IFN-gamma, and LPS did not affect
      EC-SOD synthesis. The presented data point to a cAMP-dependent pathway for the
      enhanced expression of EC-SOD by glial cells in brain.

PMID- 8886799
TI  - Protective effect of natural flavonoids on rat peritoneal macrophages injury
      caused by asbestos fibers.
AB  - Exposure of macrophages to asbestos fibers resulted in enhancement of the
      production of oxygen radicals, determined by a lucigenin enhanced
      chemiluminescence (LEC) assay, a formation of thiobarbituric acid reactive
      substances (TBARS), a LDH release into the incubation mixture, and a rapid lysis
      of the cells. Rutin (Rut) and quercetin (Qr) were effective in inhibiting LEC,
      TBARS formation, and reducing peritoneal macrophages injury caused by asbestos.
      The concentrations pre-treatment of antioxidants that were required to prevent
      the injury of peritoneal macrophages caused by asbestos by 50% (IC50) were 90
      microM and 290 microM for Qr and Rut, respectively. Both flavonoids were found to
      be oxidized during exposure of peritoneal macrophages to asbestos and the
      oxidation was SOD sensitive. The efficacy of flavonoids as antioxidant agents as
      well as superoxide ion scavengers was also evaluated using appropriate model
      systems, and both quercetin and rutin were found to be effective in scavenging
      O2.-. These findings indicate that flavonoids are able to prevent the respiratory
      burst in rat peritoneal macrophages exposed to asbestos at the stage of activated
      oxygen species generation, mainly as superoxide scavengers. On the basis of this
      study it was concluded that natural flavonoids quercetin and rutin would be
      promising drug candidates for a prophylactic asbestos-induced disease.

PMID- 8886800
TI  - Superoxide dismutase in human sperm suspensions: relationship with cellular
      composition, oxidative stress, and sperm function.
AB  - Sensitive techniques have been developed for monitoring superoxide dismutase
      (SOD) activities in human sperm preparations. In contradiction to the protective
      role normally assigned to SOD, populations of defective spermatozoa recovered
      from the low density region of Percoll gradients were found to have three times
      more SOD than functionally competent preparations pelleting in high density
      Percoll. SOD activity was negatively correlated with the movement characteristics
      of human spermatozoa and their capacity for oocyte fusion, and positively
      associated with the induction of peroxidative damage. SOD activity was also
      highly correlated with other markers of the cytoplasmic space, creatine kinase
      (CK), and glucose-6-phosphate dehydrogenase (G-6-PDH). We conclude that while SOD
      may play a physiological role in maintaining a balance between O2.- and H2O2,
      high levels of this enzyme are associated with impaired sperm function because
      (a) the human spermatozoon is highly susceptible to the cytotoxic effects of
      H2O2, (b) O2.- is an important mediator of normal sperm function, and (c) high
      SOD activities reflect errors in spermatogenesis associated with germ cell
      exfoliation and the retention of excess residual cytoplasm by the spermatozoa.

PMID- 8886801
TI  - Effect of vitamin E on human aortic endothelial cell responses to oxidative
      injury.
AB  - Reactive oxygen species produced by the cells present in the arterial wall may
      cause oxidative damage to cellular components altering endothelial cell (EC)
      function. Changes in the EC function appear to play a key role in the
      pathogenesis of atherosclerosis. Human aortic endothelial cells (HAEC) were
      employed to investigate the protective role of vitamin E upon exposure of
      endothelial cells to oxidative stress in vitro. HAEC assimilate d-alpha
      tocopherol from the media in a dose-dependent manner. Exposure of HAEC to 16.5 mM
      of the free radical generator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH)
      for 16 h decreased cell viability (assessed by trypan blue exclusion) from 90 to
      28%. HAEC preincubated with vitamin E at 15, 30, and 60 microM prior to the AAPH
      exposure resulted in a dose-dependent increase in resistance to oxidative stress
      and increased cell viability by 37, 66, and 85%, respectively. An increase in
      prostacyclin (PGI2) production by HAEC in response to AAPH exposure was
      correlated positively with cell damage and negatively with vitamin E
      concentration. Interleukin (IL)-1 production also increased in parallel with cell
      damage induced by AAPH. Vitamin E treatment significantly reduced IL-1 production
      after AAPH exposure. This modulatory role of vitamin E on HAEC function following
      exposure to an oxidative stress may reflect its antioxidant protection against
      lipid peroxidation.

PMID- 8886802
TI  - NO-induced oxidative stress and glutathione metabolism in rodent and human cells.
AB  - Nitric oxide (NO.), a radical species produced by many types of cells, is known
      to play a critical role in both regulatory processes and cell defense, yet it may
      also participate in collateral reactions, leading to DNA damage and cell death in
      both NO-generating and neighboring cells. Glutathione has been shown to protect
      cells from the toxic effects of free radicals and reactive oxygen species. The
      goal of this study was to investigate whether differences in glutathione
      metabolism could account for the resistance or sensitivity to cell killing by
      NO.. The cytotoxic effect of NO. was examined in CHO-AA8 (Chinese Hamster Ovary)
      cells and TK6 (human lymphoblastoid) cells pretreated with L-buthionine SR
      sulfoximine (BSO), a potent inhibitor of gamma-glutamylcysteine synthetase, and
      with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), an irreversible inhibitor of
      glutathione reductase. The consequences resulting from the depletion of
      glutathione levels and from the arrest of oxidoreduction allowed us to show the
      involvement of glutathione in protecting cells from NO. and to investigate the
      importance of changes in glutathione metabolism on NO-induced toxicity. In CHO
      AA8 cells, we found that treatment with NO. resulted in the oxidation of reduced
      glutathione (GSH) to oxidized glutathione (GSSG) and to mixed glutathione
      disulfides (GSSR). The resulting depletion of GSH stimulated its de novo
      synthesis, enabling the cells to resist killing by NO.. A slight difference in
      GSH metabolism was observed in TK6 cells. NO. led to an increase in GSSG levels
      similar to that observed in CHO-AA8 cells, however, a decrease in GSH levels, no
      change in GSSR levels, and higher levels of toxicity were also found, suggesting
      that NO-treated TK6 cells are not as competent in GSH homeostasis as CHO cells.
      We conclude that GSH is involved in protecting cells from killing by NO. and that
      both de novo synthesis of GSH and GSSG reduction are important in maintaining an
      adequate level of protection for the cells.

PMID- 8886803
TI  - Oxidative stress induces the levels of a MafG homolog in hamster HA-1 cells.
AB  - The Maf family encodes nuclear proteins that recognize AP-1-like response
      elements. MafB, MafK, MafF, and MafG, are all able to heterodimerize with each
      other, c-fos, and erythroid cell-specific transcription factor NF-E2, to affect
      the transcription of target genes. Using the technique of differential display,
      we recently identified a new oxidant-inducible mRNA, designated adapt66, in HA-1
      hamster fibroblasts. Cloning, partial sequencing, and GenBank analysis of adapt66
      revealed strong homology to chicken mafG, a newly identified member of the maf
      oncogene family. The mafG homolog/adapt66 mRNA induction appeared to be dependent
      upon calcium; occurred as early as 90 minutes following exposure of HA-1 cells to
      hydrogen peroxide; and peaked between 5 and 10 hours after peroxide treatment. It
      has previously been demonstrated that several cellular transcription factors,
      including Fos, can be induced by oxidative stress. The induction of the DNA
      binding sequence mafG homolog/adapt66 by hydrogen peroxide, and it's known
      interaction with c-fos, may represent important mechanisms by which oxidative
      stress can modulate gene expression.

PMID- 8886804
TI  - Manganese superoxide dismutase in human pleural mesothelioma cell lines.
AB  - Mesothelioma is a malignant pleural or intraperitoneal tumor attributable to
      asbestos exposure in more than 80% of the cases. Manganese superoxide dismutase
      (MnSOD), a mitochondrial superoxide radical scavenging enzyme, is low in most
      tumors but is known to be induced by asbestos fibers and certain cytokines.
      Induction of MnSOD may be associated in asbestos-related pulmonary diseases in
      vivo. We investigated here MnSOD specific activity and MnSOD mRNA level using
      healthy human lung tissue, SV40-transformed human pleural mesothelial cells
      (Met5A), and six human malignant mesothelioma cell line cells. Total SOD (CuZnSOD
      + MnSOD) and MnSOD activities were 20.0 +/- 4.8 U/mg protein and 3.2 +/- 1.2 U/mg
      protein in healthy human lung tissue, and 25.6 +/- 10.7 U/mg and 3.8 +/- 1.0 U/mg
      in Met5A cells, respectively. In four mesothelioma cell lines MnSOD activity was
      significantly elevated, the highest activity (30.1 +/- 8.2 U/mg) was almost 10
      fold compared to the activity in Met5A cells. The steady state mRNA level of
      MnSOD was low in Met5A cells and markedly higher in all mesothelioma cell lines
      roughly in proportion with enzyme activities. Cytotoxicity experiments, which
      were conducted in four cell lines, indicated that cells containing high MnSOD
      mRNA level and activity were resistant to the mitochondrial superoxide-producing
      agent menadione. In conclusion, our results suggest that human mesothelioma may
      express high levels of MnSOD, which is associated with high oxidant resistance of
      these cells.

PMID- 8886805
TI  - Tissue differences in antioxidant enzyme gene expression in response to
      endotoxin.
AB  - The effect of endotoxin on antioxidant gene expression and antioxidant enzyme
      activity in homogenates of the heart, liver, and kidney from Sprague-Dawley rats
      was compared by quantitation of m-RNA and enzyme activities. Alterations in the
      message level for Cu-Zn superoxide dismutase (SOD), Mn SOD, and catalase varied
      with the tissue type, length of exposure to endotoxin, and dose of endotoxin. In
      general, endotoxin treatment reduced Cu-Zn SOD expression in the heart and liver,
      but had no noticeable effect in the kidney. Mn SOD message levels were increased
      in the heart and kidney but decreased in the liver. Catalase expression was
      reduced in the kidney and increased marginally in the heart and liver. With
      regard to enzyme activity, endotoxin treatment reduced Cu-Zn SOD activity in the
      heart, liver, and kidney. Mn SOD activity showed little change in the heart, but
      increased in the liver and, to a lesser extent, in the kidney. Catalase activity
      showed little change in the heart and kidney but was decreased at 12 h in the
      liver. The differing responses of tissues to the oxidant stress of endotoxin
      exposure should be considered when evaluating the effect of endotoxin on
      antioxidant enzymes.

PMID- 8886806
TI  - Effects of exhaustive exercise and vitamin B6 deficiency on free radical
      oxidative process in male trained rats.
AB  - There is growing evidence that oxygen free radical production and subsequent
      lipid peroxidation are normal sequelae to the rise in oxygen consumption
      concomitant with exercise. In addition, increased lipid peroxidation has also
      been shown in vitamin B6-deficient rat plasma, liver, and kidney. To investigate
      the potential for a role of vitamin B6 in exercise-induced oxidative stress, 36
      male Sprague-Dawley rats received 0 (n = 12), 2 (n = 12), and 8 mg pyridoxine
      (PN)-HCl/kg diet (n = 12) and were trained by a 9-week swimming program. After 9
      weeks of training, six rats (exhausted: E rats) of each vitamin group were
      exercised to exhaustion by swimming while the other six rats rested
      (nonexhausted: NE rats). Ascorbate, ascorbate free radical and antilipoperoxidant
      capability (AC) were evaluated in plasma. These parameters were higher in E rats
      than in NE rats. Free radical-mediated lipid peroxidation was measured in tissue
      and plasma by evaluation of thiobarbituric acid reactive substances (TBARS)
      content. This index of peroxidation was significantly increased in liver of E
      rats but not in plasma, heart, and gastrocnemius muscle. Concentration of TBARS
      in liver was the highest in vitamin B6-deficient rats (consuming 0 mg PN-HCl/kg
      diet) and the lowest in vitamin B6-sufficient rats (consuming 8 mg PN-HCl/kg
      diet). Vitamin E (alpha-tocopherol) levels in liver and heart were negatively
      related to vitamin B6 levels in the diet. Independently of vitamin B6, liver and
      muscle alpha-tocopherol levels were significantly higher in E animals than in NE
      animals. There is good evidence according to our results that exercise induced an
      oxidative stress, as indicated by a significant increase of ascorbyl radical
      levels in the plasma. The effects of vitamin B6 deficiency on the free radical
      metabolism are low in trained rats. On the contrary, exhaustive exercise induced
      modifications in the metabolism pathways of vitamin C and E objectivated by
      variations of levels of vitamin C in the plasma and vitamin E in liver.

PMID- 8886807
TI  - Comparison of 5-hydroxy-2-amino valeric acid with carbonyl group content as a
      marker of oxidized protein in human and mouse liver tissues.
AB  - Previous studies indicate that 5-hydroxy-2-amino valeric acid (HAVA) is an
      excellent marker of oxidized arginine and proline in purified proteins. We report
      here experiments testing the specificity of the HAVA assay technique using the
      unpurified 100,000 x g supernatant fraction prepared from mice and human liver
      tissue. Results are compared to carbonyl group analysis on the same tissue
      samples. Mice at ages 3, 12, and 30 months were exposed to 100% oxygen. Results
      showed a significant increase of HAVA content in each age group. No significant
      changes were found in carbonyl group content. Because it has been reported that
      carbonyl group content increases with age, we applied the HAVA assay to reexamine
      this question. Using mice of 1 to 30 months of age, we failed to detect any
      significance difference in either HAVA or carbonyl group content. However, on
      using human liver samples a significant decrease from age 16 to 40 years and then
      an increase to 85 years of age was found for both HAVA and carbonyl groups. Liver
      proteins may be oxidized from hydrogen peroxide produced from the cytochrome P450
      detoxification system. This possibility was supported by a significant positive
      correlation found between HAVA and cytochrome P450 content in 18 human
      individuals of different ages.

PMID- 8886808
TI  - Increase in glutathione peroxidase activity in malaria parasite after selenium
      supplementation.
AB  - Glutathione peroxidase (GPx), a key enzyme involved in the detoxification of many
      peroxides, has been investigated in two malaria parasite species: P. yoelii in
      vivo (murine malaria) and P. falciparum in vitro (human malaria). We demonstrate
      the presence of an endogenous GPx activity in these two Plasmodia species.
      Enzymatic assays and the use of specific substrates and inhibitors allowed us to
      determine that the activity is selenium dependent. As this activity was shown to
      be lower in P. falciparum than in P. yoelii, and selenium levels were found to be
      low in culture medium and culture red blood cells, we hypothesized that a severe
      selenium deficiency could be responsible for this difference. After selenium
      supplementation, with either sodium selenite or selenocystine, we observed an
      increase in growth of P. falciparum only in with sodium selenite, whereas higher
      GPx activities were noted in parasites grown in media supplemented with both. An
      increase in GPx activities was also observed in parasites that had undergone an
      experimental oxidative stress with TBOOH. As the erythrocyte is unable to
      synthesize new proteins, these results provide further evidence for the existence
      of an endogenous parasitic selenium-dependent glutathione peroxidase.

PMID- 8886809
TI  - P-selectin is upregulated early in the course of hyperoxic lung injury in mice.
AB  - While treatment with supplemental oxygen is often essential in patients with lung
      disease, prolonged therapy may cause lung injury by itself. Although the
      mechanisms responsible for initiating hyperoxic lung damage almost certainly
      involve primary oxidative transformations, the possible contributions of
      inflammation to the tissue injury have been attracting increasing research
      activity. Increases in intercellular adhesion molecule-1 (ICAM-1) coincide with
      the inflammation, but in other models of inflammation transient adhesion mediated
      by members of the Selectin gene family was found to be essential before ICAM
      1/beta 2 interactions could occur. We, therefore, wondered whether a similar
      sequence of initial transient adhesion followed by subsequent responses would be
      observed in hyperoxic lung inflammation. We, therefore, determined the effects of
      hyperoxia exposure on lung mRNA for P- and E-Selectin in mouse lungs. We found
      that there was no detectable mRNA for E-Selectin through 72 h of hyperoxia
      exposure by Northern blotting, but that mRNA for P-Selectin was detectable as
      early as 48 h after initiation of hyperoxia. To determine the location of P
      Selectin upregulation we examined hyperoxia-exposed mouse lungs by in situ
      hybridization and found that the upregulation of P-Selectin at 48 h was localized
      to large muscularized vessels, at 72 h expression was detected in some medium
      size muscularized vessels, and at 96 h abundant expression was observed also on
      nonmuscularized small vessels. In conclusion, increases in mRNA for P-Selectin
      early in the course of hyperoxia exposure suggest that P-Selectin expression in
      hyperoxic lungs increases in parallel with upregulation of ICAM-1, leading to the
      accumulation of neutrophils in hyperoxic lungs, and that interventions targeting
      these two adhesion molecules may lead to a diminution in hyperoxic lung
      inflammation and lung injury.

PMID- 8886810
TI  - Hemodynamic adaptation to orthostatic stress after orthotopic heart
      transplantation.
AB  - OBJECTIVES: The purpose of this study was to compare the effects of orthostatic
      stress on cardiovascular stability in heart transplant recipients early and late
      after transplantation and in healthy controls. BACKGROUND: After transplantation,
      cardiac reinnervation is heterogeneous, with reports of sympathetic reinnervation
      after 5 months and parasympathetic reinnervation after 2 to 3 years. METHODS:
      Sixteen heart transplant recipients early (less than 5 months) after
      transplantation, 17 recipients late (1 year or more) after transplantation, and
      16 matched healthy controls were subjected to 45 minutes of passive upright tilt,
      with the following variables measured before, during, and after the procedure:
      cardiac output, heart rate, stroke volume, mean arterial pressure, systemic
      vascular resistance, and plasma norepinephrine. RESULTS: At rest, heart rate (p <
      0.0005) and mean arterial pressure (p = 0.003) were higher, and stroke volume was
      lower (p < 0.0005), in transplant recipients than they were in controls. With
      orthostasis, heart rate increased by 30% in controls and by 23% in the late
      posttransplantation group compared with 13% in the early posttransplantation
      group (p = 0.028); drop in stroke volume was three times more among controls than
      among those in either transplantation group (p < 0.001); late transplant
      recipients had higher norepinephrine increases than did the other two groups (p =
      0.012). CONCLUSION: With the exception of heart rate, patterns of hemodynamic
      response to orthostatic stress after transplantation remain consistent over time
      and differ from controls. Among transplant recipients, higher mean arterial
      pressure mitigates the force of gravity and prevents drops in stroke volume.
      Clinicians may anticipate that transplant recipients will tolerate postural
      maneuvers well. Later after transplantation, however, orthostatic tolerance is
      associated with increased norepinephrine release, consistent with enhanced
      sympathoactivation.

PMID- 8886811
TI  - Securing life through technology acceptance: the first six months after
      transvenous internal cardioverter defibrillator implantation.
AB  - PURPOSE: To understand the experience of living with a transvenous internal
      cardioverter defibrillator (ICD) during the first 6 months after implantation.
      DESIGN: A grounded theory approach was used to gain an understanding of the
      antecedents, conditions, and consequences of the core process. SETTING: Two
      midwestern community medical centers and patients' homes within a 250-mile radius
      from the medical centers. SAMPLE: Ten women and 14 men between 22 and 78 years of
      age, who had undergone a new transvenous ICD implantation within the last week.
      RESULTS: The core process that described the experience of living with a
      transvenous ICD during the first 6 months after implantation was the process of
      "securing life through technology acceptance." This core process was
      characterized by three major categories: choosing life with technology,
      integrating technology into life, and living life through technology.
      IMPLICATIONS: Nursing interventions related to individualized assessment,
      education, and counseling are warranted to facilitate patient and family
      understanding and to plan for the cyclic process involved in integrating a
      transvenous ICD into their lives. Directions for further research are provided.

PMID- 8886812
TI  - Effect of a postdischarge education class on coronary artery disease knowledge
      and self-reported health-promoting behaviors.
AB  - OBJECTIVE: To determine the effect of a single 2-hour postdischarge education
      class on knowledge and health-promoting behaviors of patients undergoing cardiac
      catheterization. DESIGN: Descriptive, two-group, posttest survey. SETTING:
      Midwestern community hospital. SUBJECTS: One hundred fourteen patients who had
      experienced a cardiac catheterization, 53 patients who had attended a
      postdischarge coronary artery disease education class, and 61 patients who had
      not attended the class. OUTCOME MEASURES: Knowledge of coronary artery disease
      and coronary artery disease risk factor, and health-promoting behaviors. RESULTS:
      Those who attended the postdischarge class scored significantly higher on both
      knowledge and health-promoting behaviors. CONCLUSION: Patients who attended a
      single 2-hour postdischarge education class had significantly higher knowledge of
      coronary artery disease and coronary artery disease risk factors. Knowledge may
      better prepare people to increase health-promoting behaviors.

PMID- 8886813
TI  - Common varieties of supraventricular tachycardia: differentiation and dangers.
AB  - Two major types of supraventricular tachycardia (SVT) commonly seen in acute care
      situations are atrioventricular nodal reentrant tachycardia (AVNRT), and
      orthodromic atrioventricular reentrant tachycardia (AVRT). Intranodal reentry via
      fast and slow conduction pathways within the atrioventricular junction is the
      mechanism by which AVNRT develops. In contrast, reentrant tachycardia across
      accessory pathways is associated with preexcitation and AVRT. In the setting of
      Wolff-Parkinson-White syndrome, inappropriate treatment of AVRT may result in a
      potentially lethal type of atrial fibrillation. Electrocardiographic cues that
      differentiate between AVNRT and AVRT are discussed. Treatments range from
      emergency cardioversion to administration of intravenous agents such as
      adenosine. The tachycardias may be cured with radiofrequency catheter ablation.

PMID- 8886814
TI  - Blastomycosis-induced respiratory failure: the successful application of
      continuous positive airway pressure.
AB  - A patient diagnosed with pulmonary blastomycosis was seen initially by her
      primary care physician for severe pain in her right elbow and was treated with
      steroid therapy and analgesics. She also had been treated for chronic cough and
      congestion for approximately 2 months before admission. She showed no improvement
      at home. She was hospitalized for right epicondylitis, and progressively
      worsening restrictive pulmonary symptoms developed, including hypoxemia and
      dyspnea. She was transferred to the intensive care unit and treated with mask
      continuous positive airway pressure (CPAP) and intravenous amphotericin B.
      Despite worsening hypoxemia, successful management of oxygenation was achieved
      with CPAP, averting the need for intubation and mechanical ventilation. This case
      demonstrates the usefulness of CPAP in infectious disorders that create
      restrictive lung impairment.

PMID- 8886815
TI  - Problems associated with underrecognition of delirium in critical care: a case
      study.
AB  - Delirium, a syndrome that results in high morbidity and mortality rates in the
      elderly, continues to be underrecognized by physicians and nurses. Factors
      influencing the underrecognition of delirium are specific to individual
      institutions and their health care providers. The factors leading to the
      underrecognition of delirium must be identified so that changes can be made to
      increase early recognition. A case study conducted in a critical care unit in a
      midwestern hospital from interviews of nurses, chart audit, and patient
      observation, identified two major problems associated with the lack of
      recognition of delirium in that institution: (1) lack of knowledge on the part of
      nurses about the criteria and methods of detecting delirium, and (2) ineffective
      communication between all staff members in relaying symptoms of onset of the
      disorder. As a result of this study, staff education, assessment protocols, and
      improved communication and documentation techniques are indicated as targeted
      methods for improving recognition and treatment of delirium in this setting.
      Similar case studies can be performed to evaluate institutional practice, and
      thereby identify barriers to early recognition of delirium.

PMID- 8886816
TI  - Intravascular site care: are critical care nurses practicing according to written
      protocols?
AB  - OBJECTIVE: To observe and describe site care for intravascular devices, to
      identify internurse variations in site care, and to compare written protocols for
      site care with actual practice in one geographic area. DESIGN: Observational,
      descriptive study. SETTING: Adult critical care units in one community, and one
      university teaching hospital in the Washington, D.C., metropolitan area. SAMPLE:
      Direct observation of 86 central and 30 peripheral site care episodes. RESULTS: A
      total of 116 site care episodes were observed on five critical care units. There
      were wide variations between units from the same hospital in gloving practices
      and use of aseptic technique. Significant differences across both hospitals, as
      well as between individual units, were noted for a number of other practices
      including: time since last site care, use of ointment and skin adhesive, type of
      dressing used, and duration of care. In both hospitals, compliance with all steps
      of the written protocol was similar-23.2% and 23.3%. Compliance with
      documentation requirements ranged from 53.3% to 85.7%, and was significantly
      different between the two hospitals with regard to recording the dressing change
      and whether the dressing label and chart agreed. CONCLUSIONS: Intravascular site
      care varies significantly among critical care units within the same institution,
      as well as between different hospitals, and varies from written protocol.
      Standardized, well-defined site care protocols and education of staff, along with
      quality improvement surveillance systems are needed to ensure consistent quality
      intravascular site care.

PMID- 8886817
TI  - Stress in critical care nurses: actual and perceived.
AB  - OBJECTIVE: To describe the stressful work experiences and the perception of
      stress in female critical care nurses, and to explore possible relationships
      between these variables. DESIGN: A descriptive, correlational study. SETTING: Two
      Canadian, university-affiliated, tertiary care hospitals. SUBJECTS: A convenience
      sample of 96 female nurses, with at least 1 year of critical care experience,
      currently working in adult intensive care units. INSTRUMENTS: Subjects were
      administered a demographic instrument, the Critical Care Nursing Stress Scale,
      and the Perceived Stress Scale. RESULTS: Ranking the stressful work situations
      revealed that patient care-related stressors ranked the highest overall. Although
      lack of control appeared to be a common element among those situations ranked as
      the most stressful, there was considerable diversity in the stressor rankings
      between the individual units. There were significant correlations between
      perceived life stress and the perceived severity of work stressors (r = 0.296, p
      < 0.005), as well as between actual (frequency) and perceived (intensity)
      stressful work events (r = 0.50, p < 0.001). CONCLUSIONS: This study provides
      valuable insight into the actual and perceived stressful experiences of critical
      care nurses, thus contributing to the ongoing effort to reduce burnout in this
      population. The findings also establish a foundation for further nursing stress
      research in the context of the Adaptation Nursing Model.

PMID- 8886818
TI  - Nosocomial pneumonia: problems and progress.

PMID- 8886819
TI  - Spouse stressors while awaiting heart transplantation.

PMID- 8886820
TI  - Streptococcus bovis endocarditis and vertebral osteomyelitis.

PMID- 8886821
TI  - The role of hyperglycemia in the development of diabetic complications.

PMID- 8886822
TI  - Effects of calcium channel blockers on steroidogenesis stimulated by ACTH and
      cAMP in isolated rat adrenal cells.
AB  - The effects of the calcium channel blockers verapamil, diltiazem, prenylamine and
      nifedipine on the ACTH- and cAMP-mediated pathway for steroidogenesis in a
      suspension solution of isolated rat adrenal cells were studied. Steroidogenesis
      stimulated by ACTH (10(-10) M) or cAMP (10(-3) M) was not inhibited by nifedipine
      (10(-4) M), but was strongly inhibited in a concentration-dependent manner by
      verapamil, diltiazem and prenylamine (10(-5) to 10(-4) M).

PMID- 8886823
TI  - Postprandial serum lipids and tissue lipoprotein lipase are acutely altered in
      rats by the alpha-glucosidase inhibitor acarbose.
AB  - The purpose of this study was to evaluate the consequences of the acarbose
      induced attenuation of postprandial glycemia and insulinemia on plasma lipid
      concentrations and on tissue lipoprotein lipase (LPL) activity. Rats were fed a
      high-sucrose diet ad libitum for two weeks. On the day of the experiment, half of
      the animals were given a high-sucrose meal, whereas the other half were given
      acarbose (10 mg/kg body weight) mixed with the meal. Serum lipids and tissue LPL
      activity were assessed in samples collected one hour after meal intake. Glycemia
      was comparable in both groups, whereas serum insulin in acarbose-fed rats was
      half that of control animals. The main effects of acarbose on postprandial lipids
      consisted of a lowering of triacylglycerols (-50%) and non-high density
      lipoprotein cholesterol. LPL was not altered by acarbose in white and brown
      adipose tissues, but was higher in the heart (+33%). The effects of acarbose on
      postprandial serum lipids are consistent with a slower rate of de novo
      lipogenesis from carbohydrate precursors and a consequent lowering of very-low
      density lipoprotein secretion into the circulation. In addition, the acarbose
      induced dampening of the postprandial excursion of insulin may have maintained
      higher LPL activity in the heart, which would be liable to participate in the
      hypotriacylglycerolemic action of the inhibitor.

PMID- 8886824
TI  - Androstanediol glucuronide in patients with pancreatic cancer and in those with
      chronic pancreatitis.
AB  - The differential diagnosis between pancreatic cancer and chronic pancreatitis is
      extremely difficult. Beside CA19-9 level determinations, many tests have been
      tried with the aim to facilitate this distinction. Serum androgen levels have
      been used for this purpose. To further explore the value of androgen markers in
      differentiating pancreatic cancer from chronic pancreatitis we determined the
      serum levels of androstanediol glucuronide and of androgens in the two groups of
      patients and compared them with CA19-9 levels. A total of 25 males were entered
      into the study. Of these, 13 patients had pancreatic cancer and 12 chronic
      pancreatitis. They were comparable as to their body weight and age. Patients with
      pancreatic cancer had significantly lower serum testosterone, dihydrotestosterone
      and androstanediol glucuronide levels, but not testosterone/dihydrotestosterone
      ratios when compared to patients with chronic pancreatitis. Only androstanediol
      glucuronide and dihydrotestosterone serum concentrations had such a small overlap
      between the two groups that could be used for differentiation, their sensitivity
      and specificity being comparable to those of CA19-9 levels. The present study has
      shown for the first time that serum androstanediol glucuronide levels in male
      patients with pancreatic cancer are significantly lower than in those patients
      with chronic pancreatitis. Furthermore, the sensitivity and specificity of serum
      andorstanediol glucuronide levels which can be used to differentiate between
      pancreatic cancer and chronic pancreatitis are comparable to those of CA19-9.

PMID- 8886825
TI  - The relationship between lipoprotein(a) and low density lipoprotein receptors
      during the treatment of hyperthyroidism.
AB  - To determine whether the low density lipoprotein (LDL) receptor pathway is
      involved in the catabolism of plasma lipoprotein (a) [Lp(a)], serum lipids,
      Lp(a), and LDL receptor activity were measured in seven patients with
      hyperthyroidism before and after methimazole treatment given hyperthyroidism is
      associated with enhanced LDL receptor activity. LDL receptor activity in patients
      was estimated by the equation using the serum concentrations of apolipoprotein
      (apo) B and C-II. When euthyroidism was achieved after treatment, not only did
      serum total cholesterol, high density lipoprotein-cholesterol, apo B, and LDL
      cholesterol (LDL-Ch) levels rise, but Lp(a) significantly increased and
      calculated LDL receptor activity significantly decreased. The changes in LDL
      receptor activity were significantly correlated with the changes in LDL-Ch as
      expected, but not with changes in Lp(a). These results suggest that the serum
      concentration of Lp(a) is lowered in hyperthyroidism, probably by a mechanism
      other than the enhanced activity of the LDL receptor, and that the LDL receptor
      pathway is involved in the catabolism of Lp(a) to a limited extent.

PMID- 8886826
TI  - Erythrocyte sodium-hydrogen antiport activity is not a predictor of diabetic
      nephropathy.
AB  - Erythrocyte sodium-hydrogen antiport activity was measured by Orlov's method in
      36 healthy volunteers (18 with negative, 18 with positive family history of
      hypertension) and 52 subjects with type 1 insulin-dependent diabetes mellitus: 29
      patients were without known diabetic complications, 23 patients with
      microangiopathy (10 with diabetic retinopathy, 13 with 'incipient' diabetic
      nephropathy). Normotensive healthy adults had similar antiport activities
      independently of a positive or negative family history of hypertension (6.45 +/-
      2.61 vs. 5.80 +/- 3.07 mmol/l of cells per h, respectively). Sodium-hydrogen
      antiport resulted 8.38 +/- 3.91 mmol/l of cells per h in the 29 uncomplicated
      diabetic patients, significantly higher (p < 0.05) compared to healthy subjects,
      both without and with family hypertension. Complicated diabetics confirmed to
      have an exchange rate higher than healthy controls (8.18 +/- 2.50 mmol/l of cells
      per h, p < 0.01): patients with retinopathy showed the highest antiport activity
      (8.96 +/- 2.95 mmol/l of cells per h, p < 0.01), while patients with nephropathy
      had milder antiport overactivity (7.58 +/- 2.02 mmol/l of cells per h), not
      significantly different from either uncomplicated diabetics or healthy controls.
      Thus, an increased sodium-hydrogen exchange rate in peripheral erythrocytes does
      not seem to be an early indicator of diabetic nephropathy.

PMID- 8886827
TI  - Effect of CL316,243, a highly specific beta 3-adrenoceptor agonist, on lipolysis
      of human and rat adipocytes.

PMID- 8886828
TI  - Increased growth of brown adipose tissue but its decreased lysosomal enzyme
      activity in heat-acclimatized, insulin-treated rats.

PMID- 8886829
TI  - The IL-8 production in endothelial cells is stimulated by high glucose.

PMID- 8886830
TI  - Ob gene product (leptin) and antileptin antibodies.

PMID- 8886831
TI  - Targeting gamma interferon to tumor cells by a genetically engineered fusion
      protein secreted from myeloma cells.
AB  - The construction, synthesis and expression of a genetically engineered
      bifunctional antibody/cytokine fusion protein is described. To target IFN-tau to
      tumor cells, recombinant antibody techniques were used to construct a RM4/IFN-tau
      fusion protein containing the chimeric anti-tumor F(ab')2 (RM4) and the IFN-tau
      moiety. The recombinant cDNA of IFN-tau was linked to 3 prime end of the chimeric
      heavy-chain gene fragment (M4) containing the VH, the CH1 and the hinge region to
      form the fused heavy-chain gene fragment M4-IFN-tau. Transfection of the M4-IFN
      tau gene fragment into a myeloma derived cell line VKCK which produced the
      chimeric light-chain of the same antibody, allowed the transfectant secreting the
      bifunctional fusion protein RM4/IFN-tau. The RM4/IFN-tau was purified by the
      affinity chromatography. Our data showed that the RM4/IFN-tau retained the TAG72
      antigen-binding reactivity as well as the IFN-tau activity as measured in ELISA,
      FACS analysis of cell-surface TAG72 expression, immunohistochemical study, and up
      regulation of cell-surface expression of CEA, HLA class I and class II antigens.
      Therefore, the bifunctional fusion protein RM4/IFN-tau may prove to be useful in
      targeting biological effects of the IFN-tau to tumor cells and in this way to
      stimulate the immune destruction of tumor cells.

PMID- 8886832
TI  - Cross reactive anti-tetanus and anti-melittin Fab fragments by phage display
      after tetanus toxoid immunisation.
AB  - Amino acid sequence homology between tetanus toxoid, a common vaccine and
      melittin, a bee venom allergen provided us with two antigen models for studying
      the production of cross reactive antibodies after immunisation. Analysis of the
      serum of an atopic patient recently boosted with tetanus toxoid revealed the
      presence of anti-melittin and anti-tetanus antibodies. From this donor a phage
      display Fab library was constructed five days after vaccination. Screening of
      this library either with melittin alone or with tetanus toxoid followed by
      melittin allowed the isolation of Fab fragments specific to melittin but also Fab
      fragments which cross react with melittin and tetanus toxoid. Amino acid analysis
      revealed diversity in the heavy and the light Ig chains of the melittin specific
      and of the cross reactive clones. Interestingly we found that the light chain
      recognised melittin whereas the heavy chain preferentially bound to tetanus
      toxoid suggesting that cross reactivity may be due to the different binding
      specificities of the individual Ig chains.

PMID- 8886833
TI  - Characterization of anti-tumor immunity derived from the inoculation of myeloma
      cells secreting the fusion protein RM4/IFN-tau.
AB  - Our previous study showed that the injection of mouse myeloma VKCK/RM4-IFN-tau
      cells secreting the fusion protein RM4/IFN-tau to syngeneic BALB/c mice resulted
      in tumor regression in 70% of mice after tumor inoculation. In this study, the
      VKCK/RM4-IFN-tau cell line was used to characterize the protective immunity
      subsequent to tumor inoculation. Our histologic findings demonstrated that, in
      the primary response to VKCK/RM4-IFN-tau inoculation, tumor regression is
      associated with macrophage infiltration. This macrophage-dominated regression
      further leads to a protective immunity against the 2nd challenge of parental VKCK
      tumor cells. FACS analysis and chromium release assays showed that the majority
      of T lymphocytes that mediated this anti-tumor immunity were CD8+ cytotoxic T
      lymphocytes (CTLs). Our animal studies further showed that the VKCK/RM4-IFN-tau
      cells were able to grow as aggressively as the parental VKCK cells in T
      lymphocyte deficient nude mice. The protective immunity started 7 days, became
      complete 10 days following and lasted up to at least 12 months subsequent to the
      tumor inoculation. The adoptive transfer of T lymphocyte-enriched spleen cells or
      CTLs also conferred significant protection against tumor growth of parental VKCK
      cells (p < 0.01). These data thus support the notion that genetically engineered
      tumor cells secreting IFN-tau may have potential use as tumor vaccines in
      preventing the development of tumor recurrence and/or metastases following the
      surgical removal of the primary tumors.

PMID- 8886834
TI  - Lung cancer-reacting human recombinant antibody AE6F4: potential usefulness in
      the sputum cytodiagnosis.
AB  - Human monoclonal antibody (hMAb) AE6F4 has been shown to be potentially useful
      for immunocytological detection of lung cancer cells in sputum. By recombinant
      DNA technology, IgM type hMAb AE6F4 was switched to lgG. The IgG mimic
      recombinant AE6F4 antibody expression plasmid was assembled using the antibody
      heavy chain gene, which ligated the gene encoding VH and CH1(mu) domains of hMAb
      AE6F4 heavy chain to the gene encoding CH2(gamma 1) and CH3(gamma 1) domains of
      human IgG heavy chain, and the antibody light chain gene of hMAb AE6F4. The
      recombinant antibody expressed by baby hamster kidney (BHK)-21 cells showed
      molecular size equivalence to IgG, and consisted of human mu-gamma hybrid heavy
      and kappa light chains. The immunological specificity of the recombinant antibody
      was the same as that of hMAb AE6F4 by immunoblotting analysis to the 14-3-3
      protein, the putative antigen of hMAb AE6F4, and by immunohistochemical and
      immunocytological analyses using tissue sections and sputa of lung cancer
      patients. The transfected BHK-21 cells produced the recombinant antibody
      persistently and the productivity was greater than 20 times that by human-human
      hybridoma producing hMAb AE6F4.

PMID- 8886835
TI  - A rapid method for purification of monoclonal human IgM from mass culture.
AB  - We describe in this paper the rapid and cheap purification of human
      immunoglobulin M from hybridoma supernatant of mass culture. The method consists
      of two steps: 1. concentration of supernatant by ultrafiltration and 2. dialysis
      against distilled water, pH 6.4. To produce the supernatant, the hybridomas are
      grown in RPMI media with fetal calf serum (10% FCS) in 250 ml flasks under normal
      tissue culture conditions. More than 14 mg IgM can be nearly selectively purified
      within 6 h from 5 l of antibody containing hybridoma supernatant. Most of the IgM
      molecules stay in a penta- and monomeric form and are positive in physiological
      and immunohistochemical studies.

PMID- 8886836
TI  - Unsusceptibility of recombinant human Fc fragments of immunoglobulin E to
      thrombin.
AB  - Human immunoglobulin E (IgE) contains a potential recognition sequence for
      thrombin protease cleavage at N-terminal end of C epsilon 3 domain responsible
      for binding to alpha chain of high affinity Fc receptor for IgE (Fc epsilon RI
      alpha), but it remains unknown for the enzyme susceptibility. The human Fc
      fragments of IgE (IgE-Fc), consisting of C epsilon 2' (Ala329)-C epsilon 3-C
      epsilon 4 chains (Fc') and of C epsilon 2' (Thr315-Ala329)-C epsilon 3-C epsilon
      4 chains (F(c')2), were expressed in the mammalian COS and Chinese hamster ovary
      (CHO) cells by placing the IgE-Fc cDNA under the control of the cytomegalovirus
      (CMV) promoter. Under nonreducing condition F(c')2 was not cleaved by thrombin
      protease as well as native IgE. Neither treatment of F(c')2 with final 0.1% 2
      mercaptoethanol at boiling point for 5 min, with a sulfhydryl-reactive biotin
      derivative, by which monomers in COS-derived F(c')2 preparations were
      biotinylated at Cys328, nor with neuraminidase, affected the accessibility to the
      enzyme. These results suggested that F(c')2, either dimeric or monomeric, had
      compact conformations.

PMID- 8886837
TI  - Gene transfer into hematopoietic stem cells of nonhuman primates.
AB  - Nonhuman primates provide an appropriate preclinical large-animal model to test
      the efficacy of bone marrow gene therapy procedures. Successful retroviral vector
      mediated gene transfer into monkey pluripotent hematopoietic stem cells (PHSC)
      has closed the gap between gene transfer experiments in mouse models and clinical
      application of bone marrow gene therapy. After initial bone marrow transplant
      failures, ex vivo bone marrow culture conditions were found that sufficiently
      supported maintenance of the long-term repopulating ability of genetically
      modified autologous monkey grafts. The efficiency of gene transfer into primate
      PHSC has, however, remained at least one order of magnitude lower than has been
      achieved in mice. Similar gene transfer efficiencies have been obtained with
      total bone marrow grafts, CD34+ bone marrow grafts, and mobilized peripheral
      blood progenitor cell grafts; however, various attempts to increase the
      transduction efficiency have been without significant success. Primate PHSC seem
      to require quite different culture conditions for their maintenance and
      transduction than mouse PHSC, in particular regarding hematopoietic growth factor
      addition. In contrast to observations in other species, some form of conditioning
      appeared essential for engraftment of transduced PHSC in monkeys. Although it has
      been shown that mouse retroviruses can replicate in monkeys and are capable of
      inducing neoplasms, experiments in monkeys have sufficiently confirmed the safety
      of current gene transfer procedures to allow their clinical application.

PMID- 8886838
TI  - Infection of A549 cells with a recombinant adenovirus vector induces ICAM-1
      expression and increased CD-18-dependent adhesion of activated neutrophils.
AB  - A significant number of pulmonary exacerbations in patients with cystic fibrosis
      (CF) and asthma are associated with respiratory virus infections. The molecular
      mediators of this process are beginning to be understood. Viral infection of
      respiratory epithelial cultures in vitro leads to the production of intercellular
      adhesion molecule-1 (ICAM-1) (a ligand for inflammatory cell adhesion and
      activation) and a number of proinflammatory cytokines. Human gene therapy vectors
      derived from human adenoviruses (AV) are currently under evaluation for CF
      transmembrane regulator (CFTR) gene delivery to the airway epithelium of CF
      patients. However, studies in animal models using these AV vectors demonstrate
      pulmonary inflammation following AV exposure. Using an in vitro model, we
      examined the hypothesis that exposure of respiratory epithelial cells to AV
      vectors results in upregulation of ICAM-1 gene expression. Infections were
      performed using a replication-deficient, first-generation AV vector. A549 cells
      (a human pulmonary adenocarcinoma cell line) were exposed to AV at multiplicity
      of infection of 50-150 plaque-forming units/cell (resulting in > 90% of cells
      expressing the reporter gene by 48 hr following exposure). Measurements of ICAM-1
      expression were made at time intervals following virus exposure using enzyme
      immunoassay, flow cytometry, and Northern blot analysis. Cell-bound ICAM-1 was
      significantly increased 96 hr following vector exposure, two to four times
      control, p < 0.001). The AV-exposed A549 cells also supported increased levels of
      adhesion of activated neutrophils 96 hr following AV exposure (four times
      control, p < 0.001) that was blocked by antibody to CD18. AV exposure of A549
      monolayers increases expression of biologically active ICAM-1. Strategies to
      minimize host cellular proinflammatory responses to the replication-deficient AV
      vectors may improve their safety for gene therapy.

PMID- 8886839
TI  - Molecular therapy with recombinant p53 adenovirus in an androgen-independent,
      metastatic human prostate cancer model.
AB  - The lethal phenotypes of advanced prostate cancer are androgen independent (AI)
      and metastatic to the axial skeleton. Our laboratory has developed an AI mouse
      model of metastatic human prostate cancer. In this communication, we report the
      development of tumor suppressor gene therapy in this AI and metastatic (C4-2)
      cancer model. By using recombinant adenovirus as a delivery vehicle, we
      introduced a wild-type p53 tumor suppressor gene into prostate cancer cell lines.
      Despite a silent mutation at codon 152 of the p53 gene, C4-2 cells express
      functional, but low, levels of p53 protein. However, the other prostatic cell
      lines, PC-3 and DU145, have a deletion mutation and two point mutations of the
      p53 gene, respectively. In vitro studies showed that cell growth, as measured by
      the thymidine incorporation assay, was inhibited in the C4-2, PC-3, and DU145
      cells infected with wild-type p53 adenovirus in comparison to control viruses.
      Recombinant wild-type p53 adenovirus inhibited prostate tumor growth and its
      production of prostate-specific antigen (PSA) when injected into C4-2 tumors in
      nude mice. All p53-treated mice were tumor free as long as 12 weeks after
      cessation of the 8-week treatment regimen. Two of 8 p53-treated mice developed
      small tumors growing at distant sites after a prolonged period of follow-up
      observation. Moreover, other AI prostate cancer cells, PC-3 and DU145, treated
      with Ad5-CMV-p53 failed to develop into tumors in vivo. This gene therapy
      strategy may be used against AI prostatic cancer regardless of p53 gene mutation
      status.

PMID- 8886840
TI  - Adenovirus-mediated hepatic gene transfer in mice: comparison of intravascular
      and biliary administration.
AB  - Recombinant adenoviruses have received much attention as a potential vector for
      gene therapy because of their ability to transduce many cell types with high
      efficiencies in vivo. After intravenous infusion, the majority of the vector is
      found in hepatocytes, but vector DNA is found to varying degrees in other
      tissues. In an attempt to restrict adenovirus-mediated gene transfer to the
      liver, we developed a microsurgical method that allowed for vector administration
      directly into the biliary tract of a mouse. We demonstrate that gene transfer was
      4- to 10-fold more restricted to the liver after biliary tract infusion than
      after intravascular infusion. Intravascular infusion of recombinant adenovirus
      elicits a powerful immune response that limits gene expression and the ability to
      readminister the vector. Biliary infusion resulted in a slightly lesser immune
      response as determined by the lower neutralizing antibody titers directed against
      the vector compared with animals treated by intravascular infusion. There was no
      difference in the persistence of gene expression, suggesting a similar cell
      mediated immune response against the vector containing cells in animals
      administered vector by either method. As future-generation adenovirus vectors
      that are safer and less immunogenic become available, the more liver specific
      gene transfer via the biliary tract may offer advantages over intravenous
      infusion for hepatic gene therapy.

PMID- 8886841
TI  - Detailed analysis of structures and formulations of cationic lipids for efficient
      gene transfer to the lung.
AB  - Cationic lipid-mediated gene transfer of cystic fibrosis transmembrane
      conductance regulator (CFTR) cDNA represents a promising approach for treatment
      of cystic fibrosis (CF). Here, we report on the structures of several novel
      cationic lipids that are effective for gene delivery to the lungs of mice. An
      amphiphile (#67) consisting of a cholesterol anchor linked to a spermine
      headgroup in a "T-shape" configuration was shown to be particularly efficacious.
      An optimized formulation of #67 and plasmid vector encoding chloramphenicol
      acetyl-transferase (CAT) was capable of generating up to 1 microgram of CAT
      enzyme/lung following intranasal instillation into BALB/c mice. This represents a
      1,000-fold increase in expression above that obtained in animals instilled with
      naked pDNA alone and is greater than 100-fold more active than cationic lipids
      used previously for CFTR gene expression. When directly compared with adenovirus
      based vectors containing similar transcription units, the number of molecules of
      gene product expressed using lipid-mediated transfer was equivalent to vector
      administration at multiplicities of infection ranging from 1 to 20. The level of
      transgene expression in the lungs of BALB/c mice peaked between days 1 and 4 post
      instillation, followed by a rapid decline to approximately 20% of the maximal
      value by day 7. Undiminished levels of transgene expression in the lung could be
      obtained following repeated intranasal administration of #67:DOPE:pCF1-CAT in
      nude mice. Transfection of cells with formulations of #67:DOPE:pCF1-CFTR
      generated cAMP-stimulated CFTR chloride channel and fluid transport activities,
      two well-characterized defects associated with CF cells. Taken together, the data
      demonstrate that cationic lipid-mediated gene delivery and expression of CFTR in
      CF lungs is a viable and promising approach for treatment of the disease.

PMID- 8886842
TI  - Expression of the bcl-2 gene from a defective HSV-1 amplicon vector protects
      pancreatic beta-cells from apoptosis.
AB  - It has been suggested that the mechanism of pancreatic beta-cell death in
      autoimmune diabetes mellitus and in immunoisolated transplantation devices
      involves cytokine-induced apoptosis. To explore the feasibility of a gene
      transfer strategy to protect beta-cells, we evaluated the use of replication
      defective HSV-1 amplicon vectors as gene transfer vehicles. Post-mitotic murine
      and human beta-cells were efficiently transduced by a herpes simplex virus (HSV)
      vector that expresses the reporting gene Escherichia coli lacZ under the
      transcriptional control of a HSV promoter (HSVlac) both as islets and as single
      cells. Insulin secretion, a marker of beta-cell function, was unaffected by
      HSVlac transduction of a beta-cell line. A HSV amplicon vector that expressed bcl
      2 (HSVbcl2) in beta-cells was constructed, and its effects on cytokine-mediated
      apoptosis in both a beta-cell line and primary murine beta-cells assessed by
      measuring internucleosomal fragmentation. beta-Cell apoptosis was blocked by
      transduction with HSVbcl2 but not HSVlac. The prevention of cytokine-induced
      apoptosis in beta-cells by bcl-2 expression has the potential both to ameliorate
      primary autoimmune beta-cell destruction as type I diabetes develops, and to
      prevent the destruction of transplanted beta-cells inside immunoisolation
      devices.

PMID- 8886843
TI  - Ionizing radiation greatly improves gene transfer efficiency in mammalian cells.
AB  - The vast majority of clinical protocols involving gene therapy today rely on
      viral vectors for gene transduction. The primary reason that plasmid vectors have
      not been widely used for gene therapy trials is their relatively low rate of
      stable gene transfer. We show here that ionizing radiation can improve plasmid
      transfection efficiency in both normal and neoplastic human and mouse cells. As
      high as 1,400-fold improvement in transfection efficiency can be seen in primary
      human fibroblasts treated with 9 Gy. Radiation improves transfection efficiency
      in a dose-dependent manner of only linearized plasmid DNA in transformed or
      immortalized cells, but of both linearized and supercoiled plasmid in normal
      human fibroblasts. The gene transfer dose-response curves are linear for
      neoplastic cell lines and exponential for primary cell lines. This suggests that
      radiation can improve gene integration by at least two mechanisms, one that may
      require free DNA ends and one that does not. The 2-hr delay described here, from
      the time of irradiation to the beginning of enhanced gene integration, suggests
      an inducible process that becomes active after the bulk of the radiation damage
      has been repaired. Our data further suggest that radiation may be useful to
      target human gene therapy using plasmid vectors.

PMID- 8886844
TI  - A simple and efficient method for the concentration and purification of
      recombinant retrovirus for increased hepatocyte transduction in vivo.
AB  - Although recombinant retroviruses have been widely used for the transduction of
      target organs in vivo, the viral titers achieved by current production methods
      are often too low to achieve therapeutic levels of gene expression. To overcome
      this limitation, a simple method for the efficient concentration and purification
      of amphotropic retrovirus particles was developed. After portal vein infusion
      into partially hepatectomized rats of 5.5 x 10(7) cfu of a beta-galactosidase
      (beta-gal)-expressing retrovirus (LX/beta geo) concentrated by this method, up to
      25% of hepatocytes stained positive for beta-Gal activity. Measurement of human
      alpha 1-antitrypsin (hAAT) levels after infusion of various doses of a similarly
      concentrated retrovirus encoding hAAT (LX/hAAT) demonstrated that viral
      transduction increased proportionally with titer, up to a dose of 7.5 x 10(7) cfu
      per rat. The ability to concentrate retroviral virion efficiently from large
      volumes of supernatant has allowed the further purification of virus particles by
      sucrose banding ultracentrifugation. This procedure results in a greater than 50%
      recovery of infectious virus particles, with titers up to 500-fold higher than in
      the original supernatant. These methods may have significant utility in both ex
      vivo and in vivo retroviral applications in human gene therapy.

PMID- 8886845
TI  - Construction of human factor IX expression vectors in retroviral vector frames
      optimized for muscle cells.
AB  - Development of a highly refined human factor IX (hFIX) expression vector system
      is critical for establishing a durable hemophilia B gene therapy. Here we report
      construction of a series of retroviral vectors and identification of an optimal
      basic structure and components for expressing hFIX in skeletal muscle cells.
      These vectors, which are derived from Moloney murine leukemia virus (MoMLV) with
      its enhancer sequence in the 3' long terminal repeat (LTR) deleted, contained
      internal hFIX expression units inserted in forward configuration without or with
      a viral vector intron sequence (pdL or pdLIn vector frame, respectively) or in
      inverted configuration without a viral vector intron sequence (pdLi frame).
      Internal expression units contained a hFIX cDNA or hFIX minigene (hIXm1 or hIXm2)
      derived from the hFIX cDNA by insertion of a shortened first intron sequence of
      the hFIX gene. Regardless of the promoter and vector frame used, both hIXm1 and
      hIXm2 gave 10- to 14-fold higher hFIX expression compared to those with hFIX
      cDNA. Internal hFIX transcriptional control units of these vectors were composed
      of various promoters linked with or without the muscle creatine kinase enhancer
      (Me) sequence. Promoters tested included those of alpha-actin (alpha A775), beta
      actin (beta A280), cytochrome oxidase (CO1250 and CO650), myogenin (Mg1031 and
      Mg353), and Rous sarcoma virus (RSV). beta A200, which was derived from beta A280
      by eliminating potential polyadenylation sites, was also tested. As extensively
      examined with the myogenin promoter, presence of one or multiple copies of Me in
      the vectors elevated the expression activity in myotubes by 4.5- to 19-fold over
      those without Me, but not significantly in myoblasts. Similar enhancements in
      expression activity with Me were also observed with other promoters, except those
      of RSV and CO. The latter two showed only modest enhancements in the presence of
      Me. As assayed with myotubes in culture, the general order of hFIX expression
      activity of various promoters with four copies of Me in the three different
      vector frames was beta A280 approximately beta A200 > Mg353 > Mg1031
      approximately RSV approximately CO650 approximately alpha A775 > CO1250. One
      exception was that CO650 showed significantly less activity in pdLi-type vectors
      than in the pdLIn vectors. Based on the systematic analyses of various structural
      components, a group of pdLi vectors consisting of beta A200, two to four copies
      of Me, and hIXm2 was identified to have the optimal basic vector structure to be
      used in retrovirus for hFIX expression in differentiated skeletal muscle cells.
      The present studies provide the critical first step for establishing a highly
      refined hemophilia B gene therapy based on skeletal muscle-targeted hFIX gene
      transfer.

PMID- 8886846
TI  - Gene transfer into fetal rat intestine.
AB  - To assess the fetal intestine as a site for gene therapy, we have explored a
      xenograft model in which fetal rat intestine is grafted subcutaneously into nu/nu
      mice. Prior to grafting, the tissue was exposed to a replication-deficient
      retroviral vector bearing the neo gene. Transduction efficiency was assessed by
      quantitative polymerase chain reaction (PCR) of neo in DNA recovered from the
      grafts. Three methods of infection were employed: (i) simple flushing of the
      fetal intestine with the vector; (ii) incubation with the vector for 2 hr; and
      (iii) a combination of both. The first method gave the highest transduction
      efficiencies in terms of both the proportion of samples that were neo-positive
      and the number of neo-positive cells per sample. Using this approach, the time
      course of persistence of neo-positive cells was analyzed by collecting grafts at
      1 versus 3 weeks post-infection. The results showed approximately five-fold more
      positive cells at the earlier time point than at the later, suggesting loss of
      transduced cells due to cell turnover. Nevertheless, the persistence of a portion
      of the positive cells for at least 3 weeks is encouraging for future studies with
      fetal intestine.

PMID- 8886847
TI  - Humoral response after administration of E1-deleted adenoviruses: immune
      privilege of the subretinal space.
AB  - An important limitation of E1-deleted recombinant adenoviruses in gene therapy is
      the immune response that they engender and that rapidly destroys transduced
      cells. Transduced cells of the outer retina appear to be an exception. To
      determine whether differences in immune sequestration of the outer retina
      contribute to the increased stability of transgene expression in this tissue, we
      examined the systemic humoral response to an E1-deleted adenovirus injected into
      the subretinal space. Subretinal injection of Ad.CMVlacZ in mature
      immunocompetent mice resulted in minimal circulating antibody production. In
      contrast, subcutaneous administration of equivalent doses of Ad.CMVlacZ resulted
      in high-titer antibody production against adenoviral proteins. Circulating
      antibodies in systemically immunized animals had minimal effect on retinal
      transgene expression patterns measured 2 weeks after subretinal injection of
      Ad.CMVlacZ. Histologic examination showed minimal retinal toxicity attributable
      to subretinal adenovirus in naive or immunized mice, although 3/18 (14%) of eyes
      from the latter set contained a localized granulomatous infiltrate at the ocular
      injection site. The data demonstrate that the subretinal space is an immune
      privileged site regarding humoral immunity. Further, short-term transduction
      efficiency is not affected by the presence of anti-adenoviral antibodies. The
      retina may be a favorable environment for replication-defective virus-mediated
      genetic therapy.

PMID- 8886848
TI  - Expression of co-stimulatory molecules by tumor cells decreases tumorigenicity
      but may also reduce systemic antitumor immunity.
AB  - Many tumor cells do not express co-stimulatory molecules, and this may account,
      in part, for their poor ability to stimulate T cells directly. One strategy to
      enhance immune recognition would be to express such molecules on the tumor cell.
      Here, we show that expression of a member of the B7 family of co-stimulatory
      molecules by CMT93 murine colorectal tumor or 1735 murine melanoma cells resulted
      in a local antitumor response in immunocompetent mice. The antitumor effect was
      diminished in athymic nude mice, indicating that T cells played an important part
      in this response. The ability of the B7-expressing tumor cells to generate
      systemic protective immunity was investigated by excision of tumors that
      developed from the initial inoculation followed by rechallenge with parental
      tumor cells. CMT93 is a poorly immunogenic tumor and no significant systemic
      immunity was elicited by the expression of B7-1 in these cells. 1735 melanoma is
      a mildly immunogenic tumor. Unexpectedly, the systemic immunity obtained with
      1735 tumors expressing B7-1 or B7-2 was weaker than that generated by parental
      1735 cells (p < 0.001, stratified logrank test), even when coexpression of
      interferon-gamma in the B7-1 cells produced high levels of surface MHC class I
      expression. These results suggest that some caution is appropriate when
      considering the use of these molecules in the gene therapy of cancer.

PMID- 8886849
TI  - Gene therapy in the United States: a five-year status report.

PMID- 8886850
TI  - The in vivo and in vitro effects of an alkylating agent, mechlorethamine, on IL-6
      production in mice and the role of macrophages.
AB  - Alkylating agents, cyclophosphamide (CY) and the related compound mechlorethamine
      (NM), significantly increase in vivo the blood level of IL-6 but not of IL-1.
      Since in vitro CY is inactive we have used in our experiments NM, a compound
      structurally and functionally related to phosphoramide mustard, the natural
      biologically active metabolite of CY. Thioglycollate or oil-induced peritonal
      macrophages (Mf) of four different mouse strains treated with NM produce
      significantly more IL-6 than the non-treated cells. In contrast, under these
      conditions, the production of IL-1, TNF alpha and NO/NO2 radicals is not
      affected. The NM-induced elevated production of IL-6 by Mf could not be further
      increased by the treatment of cells with LPS, which may suggest that both
      agonists stimulate the same signalling pathway. The antineoplastic activity of
      the alkylating agents like CY or NM is usually attributed to the interstrand
      cross-linking of the DNA of the dividing cells. Our experiments can be
      tentatively interpreted as the induced overplus of IL-6 can also contribute to
      the stimulation of the cytotoxic NK-cells.

PMID- 8886851
TI  - Selective inhibition of the alternative complement pathway by sCR1[desLHR-A]
      protects the rabbit isolated heart from human complement-mediated damage.
AB  - Evidence is presented that treatment with a selective inhibitor of the
      alternative complement pathway, sCR1[desLHR-A], protects the ex vivo perfused
      rabbit heart from human complement-mediated injury. Hearts from male New Zealand
      white rabbits were perfused in the Langendorff mode. After equilibration, normal
      human plasma was added to the perfusate as a source of complement. Concomitant
      with the addition of human plasma, vehicle (n = 13), soluble complement receptor
      type 1 (sCR1) (n = 10), or sCR1[desLHR-A], a truncated version of sCR1 that lacks
      the C4b binding region (n = 10) was included in the perfusate. Hemodynamic
      variables were obtained for all groups before (baseline) and after the addition
      of human plasma. Compared to vehicle-treated hearts, variables recorded during
      perfusion with human plasma including coronary perfusion pressure, left
      ventricular developed pressure, and left ventricular end diastolic pressure,
      along with a reduction of creatine kinase efflux, were improved in hearts
      perfused with either complement inhibitor. In addition, in vitro hemolysis assays
      were utilized to discriminate between the classical and alternative pathways. The
      addition of sCR1 to human serum prevented both the classical and alternative
      pathway-mediated hemolysis while sCR1[desLHR-A] prevented only the alternative
      pathway-mediated lysis. This study indicates that deletion of the C4b-binding
      site from sCR1 results in a new pharmacological moiety, sCR1[desLHR-A], that
      primarily inhibits the alternative pathway of human complement.

PMID- 8886852
TI  - The production of superoxide anion and nitric oxide by cultured murine leukocytes
      and the accumulation of TNF-alpha in the conditioned media is inhibited by
      taurine chloramine.
AB  - Taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) by activated
      peritoneal macrophages and attenuates accumulation of tumor necrosis factor-alpha
      (TNF-alpha) in the culture media, similar to that previously reported for
      activated RAW 264.7 cells. In addition, the effect of Tau-Cl and taurine on
      superoxide anion (O2-) production in murine peritoneal exudate polymorphonuclear
      leukocytes (PMN) was examined. Tau-Cl inhibited O2- production in a manner that
      was dose-dependent and reversible. Taurine also inhibited O2- production by
      stimulated PMN, but at higher concentrations and to a lesser extent than Tau-Cl.
      The effects of taurine on O2- production was attributed to the in vitro formation
      of Tau-Cl catalyzed by PMN associated halide-dependent myeloperoxidase. In
      contrast, production of NO by activated peritoneal macrophages and accumulation
      of TNF-alpha in the media was inhibited by Tau-Cl while taurine was without
      effect. These data lend support to the notion that Tau-Cl may participate in the
      inflammatory response by modulating production of inflammatory mediators.

PMID- 8886853
TI  - Effect of cortisol and ACTH on corticosteroid-suppressed peripheral blood natural
      killer cells from healthy volunteers and patients with Crohn's disease.
AB  - Recently, we have shown that administration of adrenocorticotropic hormone (ACTH)
      to corticosteroid-treated Crohn's disease (CD) patients increased the peripheral
      blood natural killer (NK) cell activity which was suppressed by the
      corticosteroids. To elucidate this observation we analysed the in vitro effect of
      budesonide, prednisolone, cortisol, and ACTH on NK cells of healthy volunteers
      and corticosteroid-treated CD patients. Incubation of peripheral blood
      mononuclear cells (PBMNC) from healthy volunteers during the cytotoxicity assay
      caused a dose-dependent inhibition of NK cell activity by the three
      corticosteroids, while ACTH had hardly any effect. Pre-incubation for 18 h with
      high and low inhibiting concentrations also showed a significant inhibiting
      effect on NK cell activity of the corticosteroids. The percentage of CD56+ NK
      cells tended to increase after pre-incubation with a high inhibiting
      concentration of budesonide, prednisolone, and cortisol. Incubation of budesonide
      or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with
      ACTH and/or cortisol, to mimic the in vivo situation, did not restore the
      corticosteroid-induced suppression of NK cell activity. The increase of the
      budesonide- or prednisolone-suppressed NK cell activity after in vivo
      administration of ACTH to the CD patients is therefore probably not a direct
      effect of cortisol or ACTH. Presumably other factors like cytokines and/or
      neurohormones must be involved in the in vivo interaction between
      corticosteroids, ACTH, and NK cells.

PMID- 8886854
TI  - Suppression of adjuvant arthritis by kappa-opioid receptor agonist: effect of
      route of administration and strain differences.
AB  - It is well established that kappa-opioid receptor agonists exert antiinflammatory
      and antihyperalgesic effects during nonspecific inflammation as well as
      suppressive effects on the development of humoral and cell-mediated immune
      responses to foreign antigens. The aim of this study was to investigate the
      ability of the kappa-opioid receptor agonist MR 2034 to modulate adjuvant
      arthritis in the rat. In the first series of experiments, treatments of Wistar
      rats were performed using several routes of drug administration: intraperitoneal
      (ip), intracaudal (ic), intracerebroventricular (icv) and intraplantar (ipl). MR
      2034 significantly suppressed joint swelling after ip and ic treatment, slightly
      reduced inflammation after ipl treatment, and did not produce any effect after
      icv treatment. In the second series of experiments, the suppressive effect of ip
      injected MR 2034 was investigated using Wistar, Dark August (DA) and Lewis rats.
      In Wistar rats, MR 2034 significantly decreased the incidence of adjuvant
      arthritis, and suppressed mean joint score and aggregate joint score. Similarly,
      in DA rats treated with MR 2034, mean arthritic score was significantly
      suppressed, but other clinical parameters were not affected. In Lewis rats,
      however, ip treatment with MR 2034 failed to produce any suppressive effect on
      joint disease and even potentiated the initial development of arthritis. These
      data suggest that immunosuppressive and antiinflammatory action of MR 2034
      markedly depend on the route of drug administration and strain susceptibility to
      opioids.

PMID- 8886855
TI  - Thymosin alpha 1 interacts with the VIP receptor-effector system in rat and mouse
      immunocompetent cells.
AB  - Thymic peptide thymosin alpha 1 (10(-11) to 10(-6) M) is shown to interact with
      the VIP receptor-effector system in rat and mouse peritoneal macrophages, and
      both rat peripheral blood lymphocytes and spleen lymphocytes. In all models,
      thymosin alpha 1 inhibits 125I-VIP binding with a potency that is in a range 1000
      1700 times lower than that of the native VIP. Interaction of thymosin alpha 1
      with VIP receptors is compared with that of some structurally VIP-related
      peptides such as helodermin, PHI, secretin, and glucagon. The order of potency in
      inhibiting 125I-VIP binding was VIP > helodermin > PHI > secretin > thymosin
      alpha 1. Thymosin alpha 1 (10(-10) to 10(-6) M) was weak in stimulating adenylyl
      cyclase activity. Its efficacy is in a range 900-1800 times lower than that of
      native VIP in all cell types studied. The analysis of the sequence of both
      complete and N-terminal portion of thymosin alpha 1 reveals close structural and
      physicochemical similarities with the members of the so-called VIP family of
      polypeptides. Taken together, experimental data support that thymosin alpha 1
      must be included like the lowest partial agonist of the VIP family of
      polypeptides and it is a VIP receptor antagonist with weak intrinsic activity.

PMID- 8886856
TI  - Kinetics of local immune responses in mouse Peyer's patches after respiratory
      exposure to flour.
AB  - Peyer's patches play a major role in the initiation of mucosal immune responses
      since most environmental antigens gain access to the digestive tract and are
      therefore liable to achieve contact with their specialized dome epithelium. We
      investigated kinetics of immunophenotypic modifications induced in the cells from
      murine Peyer's patches in a model of intensive controlled exposure to flour dust.
      Three groups of mice were placed in an atmosphere enriched in wheat flour for 3,
      6 or 10 consecutive days. Although Ig bearing B cell numbers did not vary, the
      numbers of IgA-containing plasma-cells increased significantly during the course
      of exposure. A significant and increasing imbalance of the CD4/CD8 ratio was
      noted, as early as after 3 days of exposure related both to increasing numbers of
      CD4+ and decreasing numbers of CD8+ cells. These data indicate a rapid kinetics
      of immune responses in Peyer's patches in an original model of controlled
      respiratory challenge.

PMID- 8886857
TI  - Effects of interleukin-1 beta on scanning electron microscopic appearance and
      thyroid peroxidase content of human thyrocytes in monolayer culture.
AB  - Interleukin (IL-1), an inflammatory cytokine that is detected in the thyroid
      tissues of patients with autoimmune thyroiditis, is believed to be involved in
      the disease process. To clarify the role of IL-1 in the development of autoimmune
      thyroiditis, we investigated the effects of interleukin-1 beta (IL-1 beta) on the
      morphology of human thyrocytes in monolayer culture as well as the effect on
      thyroid peroxidase (TPO) content of these cells. Human normal thyrocytes were
      cultured with IL-1 beta for 4 days in the presence and absence of TSH. In
      morphologic studies, cultured cells were fixed for examination by scanning
      electron microscopy and for immunofluorescent staining of acting filaments. IL-1
      produced striking morphologic changes in the cultured thyrocytes, including the
      cytoplasmic retraction and dissociation and/or depolymerization of actin
      filaments. These changes were unrelated to TSH stimulation. For detection of TPO,
      cultured cells were stained by an immunofluorescent technique and analyzed by
      fluorescence photometry. IL-1 reduced the TPO content and inhibited the TSH
      induced increase in TPO in a concentration-dependent manner. These morphological
      changes and the reduction in TPO content of cultured thyrocytes suggest that IL-1
      modulates the pathophysiology of autoimmune thyroiditis.

PMID- 8886858
TI  - Effects of alpha 1-acid glycoprotein on tissue factor expression and tumor
      necrosis factor secretion in human monocytes.
AB  - Activated monocytes express tissue factor (TF) and secrete tumor necrosis factor
      alpha (TNF alpha), which are important in the initiation of blood coagulation and
      inflammation. We investigated the effect of alpha 1-acid glycoprotein (alpha 1
      AGP), an acute phase protein, on the induction of the expression of TF and the
      secretion of TNF alpha in human monocytes in vitro. The TF activity of both fresh
      human monocytes and human monocytic cell line U937 significantly increased in a
      dose-dependent manner after a 6 h incubation with human or bovine alpha 1-AGP.
      The activity of TF gradually tailed off after 24 h. RT-PCR and Southern blot
      analysis revealed that TF mRNA synthesis was induced in monocytes. Inhibition of
      alpha 1-AGP induced TF expression by actinomycin D (ActD) further support that de
      novo TF mRNA synthesis was required. The specificity of the alpha 1-AGP-induced
      TF activity was demonstrated by anti-alpha 1-AGP antibody inhibition. TNF alpha
      secretion in alpha 1-AGP stimulated monocytes was also increased; this could be
      blocked by pentoxifylline (PTX). The possible contamination of lipopolysaccharide
      (LPS) in the alpha 1-AGP was excluded by limulus amoebocyte lysate. Therefore,
      these results indicate that alpha 1-AGP may contribute to the cellular initiation
      of coagulation and inflammation by increasing TF expression and TNF alpha
      secretion of monocytes.

PMID- 8886859
TI  - Haloperidol and spiperone potentiate murine splenic B cell proliferation.
AB  - The neuroleptics haloperidol and spiperone potentiated anti-mu induced murine B
      lymphocyte proliferation in vitro and lowered the threshold of anti-mu antibody
      needed to trigger proliferation. Because haloperidol and spiperone are best known
      for actions at D2, 5HT2, alpha 1 and sigma (sigma) receptors, a series of
      agonists and antagonists of these receptors were tested. Dopamine and
      norepinephrine inhibited, and serotonin (5HT) enhanced B-cell proliferation.
      Spiperone opposed the suppression of proliferation by dopamine and
      norepinephrine. However, antagonists of D1, D2, D3, D5, 5HT2, 5HT1A, and alpha 1
      receptors did not mimic the effect of haloperidol and spiperone. Furthermore, a
      series of sigma agonists failed to affect B-cell proliferation. Therefore it is
      likely that the effects of haloperidol and spiperone are not due to actions at
      known dopamine, 5HT, alpha 1, or sigma receptors. These findings indicate
      neuroleptics act not only in the CNS, but also directly on B-lymphocytes of the
      immune system. The pharmacological site of this action is not clear at this time.

PMID- 8886860
TI  - Role of P-selectin in the early stage of the Arthus reaction.
AB  - P-selectin is rapidly translocated to the surface of endothelial cells and
      platelets following exposure to chemical mediators such as histamine, thrombin
      and complement factors. The Arthus reaction is caused by vascular injury which is
      initiated by the local deposition of the immune complex followed by the
      activation of complement and release of chemical mediators. In this report, the
      role of P-selectin in the early stage of reverse passive Arthus reaction in rat
      using monoclonal antibodies (mAbs) against rat P-selectin will be investigated.
      Intravenous administration of the mAb ARP2-4 significantly attenuated paw edema 1
      h after challenging it with antigen by 31.5% (1 mg/kg) and 44.7% (3 mg/kg),
      respectively. Edema formation was also reduced by sulfatide (73.1%, 50 mg/kg) and
      inositol hexakisphosphate (InsP6) (72.9%, 30 mg/kg), which have been reported to
      block P-selectin-mediated neutrophil adhesion. Moreover, neutrophil accumulation
      into the inflammatory site in the Arthus reaction was inhibited by anti-P
      selectin mAb. P-selectin expression was detected along vessel walls prior to
      neutrophil accumulation, as determined by immunohistochemical staining using the
      antibody. In addition, the expression of P-selectin mRNA was induced 4 h after
      deposition of immune complex. From these results, we concluded that P-selectin
      plays an important role in the pathogenesis of the Arthus reaction especially in
      the early stage by recruiting neutrophils into sites of inflammation.

PMID- 8886861
TI  - Induction of selective cell death targeting on mature T-lymphocytes in rats by a
      novel immunosuppressant, FTY720.
AB  - A novel immunosuppressant, FTY720, induces a rapid and marked decrease of
      peripheral lymphocytes, and prolong allograft survival in rats. Its mechanism of
      action is mediated by apoptotic cell death. In this study, we determined the time
      related changes in the numbers of total lymphocytes, and the ratios of lymphocyte
      subpopulations in peripheral blood and lymphomyeloid organs in rats after the
      single oral administration of FTY720 (10 mg/kg), comparing with the effects of
      cyclophosphamide (80 mg/kg, ip). Total number of peripheral lymphocytes decreased
      significantly 3 h after the administration of the drug, while that of
      polymorphonuclear cells increased. T-cells were markedly decreased in number and
      reached a minimum of 2.3% of the control 3 days after the treatment, while B
      cells reached 19.7%. T-cells decreased in spleen and liver but there was no
      notable change in thymus, lymph nodes, and bone marrow. The susceptibility of the
      cells against the drug was variant based on the type and the source of cells in
      vitro. Polymorphonuclear cells were the most resistant and lymph node cells the
      most sensitive to FTY720 after 3 h incubation with different concentration of the
      drug (1, 10,100 mumol/l). When incubated with 10 mumol/l of FTY720, B-cells were
      significantly higher in viability than the whole T- or CD4-cells. These results
      demonstrated that FTY720 induces cell death selectively in mature T-lymphocytes,
      especially CD4-lymphocytes, in peripheral blood without the depression of bone
      marrow.

PMID- 8886862
TI  - The contribution of histamine to the action of bradykinin in the human nasal
      airway.
AB  - Bradykinin, 10 to 1000 micrograms given by aerosol into the nasal cavity of
      normal, healthy volunteers, produced a dose-related increase of nasal airway
      resistance. Bradykinin also reduced the minimal nasal cross-sectional area
      (Amin), increased albumin release into nasal lavage fluid and increased the
      symptoms of nasal inflammation. Pretreatment with cetirizine (10 mg orally)
      reduced the fall in Amin induced by bradykinin, 300 micrograms, but not by
      bradykinin, 100 micrograms. Pre-treatment of the subjects with the H1 histamine
      receptor antgonist cetirizine (10 mg, orally) or terfenadine (60 mg, orally) 3 h
      before bradykinin administration caused significant reduction of the bradykinin
      induced increase in nasal airway resistance in the upper range of bradykinin
      doses (300-1000 micrograms) but not in the lower range (10-100 micrograms).
      Cetirizine reduced the albumin release into the nasal airway and the symptoms
      induced by bradykinin, 1000 micrograms. Following nasal challenge with bradykinin
      300 micrograms or 1000 micrograms, no increase could be detected in the histamine
      content of nasal lavage fluid. Isolated human nasal cells released histamine in
      response to bradykinin, 33 and 100 microM, anti-IgE and calcium ionophore,
      A23187. We conclude that the actions of bradykinin in the human nasal airway are,
      in part, accounted for by the release of histamine.

PMID- 8886863
TI  - Caries prevention. A continued need worldwide.
AB  - This paper provides a global perspective of the changing prevalence, severity,
      distribution and pattern of dental caries. The prevalence of caries in children
      and adolescents has declined in most developed countries and it is now a minority
      of young people who experience most of the disease. All forms of caries have
      reduced in prevalence but pits and fissures are the surfaces most frequently
      involved. The caries experience and levels of edentulousness in the adult
      populations of developed countries have also declined. The prevalence of caries
      in adults is remarkably constant with age but in older subjects root caries is
      becoming more prevalent. However, in many developing countries the prevalence of
      caries in young children is high and is increasing in those populations who are
      adopting a cariogenic diet. In countries such as Kenya and China, caries is the
      major cause of tooth loss but levels of edentulousness are low. There are
      considerable variations in disease levels between and within countries and it is
      evident that lower socio-economic and certain racial groups exhibit high levels
      of dental caries. It is essential to sustain the benefit of fluoride to those
      already receiving it and encourage the use of appropriate and effective
      strategies and products by those who are not. Water and salt fluoridation should
      be implemented where deemed feasible and the use of a clinically proven and
      affordable fluoride toothpaste should be encouraged.

PMID- 8886864
TI  - Long-term survival and cost-effectiveness of five dental restorative materials
      used in various classes of cavity preparations.
AB  - This retrospective study examined the survival and cost-effectiveness of five
      different types of dental materials used to restore various classes of cavity
      preparations in permanent teeth. Information on the restorations was obtained
      from the casenote records of 100 long-term adult patients treated at various
      times by 20 dentists in three city practices. Patients attended for checkups and
      restorative treatments on a regular basis for around 25 years on average, ranging
      from 10 to 46 years. All of the restorative materials lasted well, despite the
      frequent patient checkups and changes of dentists. Cusp-covered amalgams were
      approximately 3.8 times more cost-effective than were either cast gold or
      ceramometal crowns, and resin composites were approximately 3.7 times more cost
      effective than were cast gold inlays for restoring Class IV preparations.
      However, there were no significant differences found in the cost-effectiveness of
      using either resin composites or glass-ionomer cements to restore Class III
      preparations, or between using either of these two materials, or amalgams, to
      restore Class V preparations.

PMID- 8886865
TI  - Endodontic failures--changing the approach.
AB  - The underlying reason for endodontic failures is almost invariably due to
      bacterial infection. The bacteria may be situated within a previously missed or
      uninstrumented portion of a root canal, infiltrate via a leaky coronal
      restoration and root filling, or cause contamination from an extra-radicular
      infection. Management of the failing root canal filling begins with the
      identification of the source of persistent infection. Should the infection be
      present within the root canal system, such as a missed canal, orthograde
      retreatment is the choice of treatment. This is also true for asymptomatic cases
      which had been inadequately obturated and which require the placement of a dowel
      into the canal for restorative reasons. Periapical surgery is best reserved for
      cases with no sign of healing after orthograde retreatment and those with extra
      radicular infection. This paper discusses the relationship between endodontics
      and restorative dentistry, treatment planning for endodontic failures, and the
      reported rates of success with orthograde and surgical retreatments.

PMID- 8886866
TI  - Productivity among Australian private general dental practitioners across a ten
      year period.
AB  - Historical trends in Australia have shown declining levels of dentists' annual
      productivity from the 1960s to the 1980s. In a period of changing population
      demographics and oral health status appropriate levels of supply of dental
      services remains a key issue. Changes in practice patterns of dentists, through
      variables such as productivity, may influence the capacity to supply services.
      The aim of this study was to investigate time trends in productivity for private
      general practitioners at three points in time across a ten year period. A
      weighted, stratified random sample of Australian dentists was surveyed in 1983-84
      (response rate 73 per cent), 1988 (response rate 75 per cent) and 1993-94
      (response rate 74 per cent). The data were re-weighted to provide representative
      estimates for the age by sex distribution of private general practitioners in
      1983, 1988 and 1993. Analysis of variance showed that the number of patient
      visits per year declined across the ten year period, related to parallel
      decreases in the number of patients treated per hour, while there was no
      significant difference during the period in the number of hours per year devoted
      to work.

PMID- 8886867
TI  - Occlusion in temporomandibular disorders: treatment after occlusal splint
      therapy.
AB  - The concept of using the condylar path as the reference for occlusion is
      questionable for the patient whose temporomandibular joint has pathological
      changes because the condylar path of TMD patient deviates greatly. After occlusal
      splint therapy it is suggested that the patient's occlusion be treated using the
      Twin-Stage Procedure which does not require measurement of the condylar path. The
      research findings that occlusion controls the condylar path seems to support the
      concept that if the dentist creates the occlusion properly, the condylar path may
      be corrected and thereby minimise the micro-trauma which causes TMD.

PMID- 8886868
TI  - Periodontal status and treatment needs in a rural area of Ukonga, Tanzania.
AB  - The study reported here assessed the periodontal status in Ukonga using the CPITN
      index in the oral health survey data collected in 1988, and subsequently
      estimated the treatment needs in relation to Tanzanian circumstances. The
      resultant calculations showed that the estimated need was far greater than the
      dental services could supply. The authors therefore question whether or not all
      persons with a positive CPITN score do need treatment and speculate that there
      may be a more realistic approach using other models.

PMID- 8886869
TI  - Periodontal conditions in 15-19-year-old Chileans.
AB  - A CPITN survey involving Chilean high school students aged 15-19 years was
      conducted. A random stratified sample by age, sex and socio-economic status was
      obtained, and comprised 2400 subjects. The total prevalence of periodontal
      disease (Code 3+4) was 10.49 per cent. There was a significant difference in the
      prevalence of periodontal disease in males (9 per cent) compared to females
      (12.16 per cent). The prevalence of periodontal disease was higher in students of
      low socio-economic status (15.87 per cent) than in students of middle (9.22 per
      cent) and high socio-economic status (8.93 per cent). The periodontal treatment
      needs were also higher for students of low socio-economic status than for
      students of the highest family income. The prevalence of periodontal disease and
      treatment needs found in Chilean students showed that virtually this entire
      population needs oral hygiene instruction, that 70 per cent need scaling, and
      that 10.49 per cent need complex periodontal treatment.

PMID- 8886870
TI  - Traumatised primary teeth in Nigerian children attending University Hospital: the
      consequences of delays in seeking treatment.
AB  - The objectives of this study were to investigate the occurrence, causes, types
      and severity of trauma to primary teeth in a hospital population, and to evaluate
      the interval between injury and treatment. The records of 1809 children treated
      in a two year period at the Ibadan University College Hospital were reviewed.
      There were 122 children aged one to seven years, with the highest frequency of
      trauma in the four and five year age groups, with no significant difference
      between boys and girls. Falls (88 per cent) were the commonest cause, and 57
      children (47 per cent) had two injuries per episode of trauma. The majority (94
      per cent) were luxation injuries and 6 per cent were fractures. Eighty-nine per
      cent of the injuries affected the maxilla, and the maxillary central incisors
      were the most frequently affected teeth, accounting for 68 per cent of all
      injuries. Only 11 per cent of the injuries presented for treatment on the day of
      trauma, while 10 per cent presented later than one year after trauma. The results
      suggest that the parents of these children with dental trauma do not bring the
      children for early treatment. The findings underscore a need to improve oral
      health awareness in general, but more importantly they emphasise that parents
      should obtain treatment for their children as soon as possible following any
      episode of dental trauma.

PMID- 8886871
TI  - Site of the mandible prone to trauma: a two year retrospective study.
AB  - The objectives of this retrospective study were to determine the most common site
      of trauma to the mandible observed at an urban centre. The study, completed at
      the Manchester Royal Infirmary UK, comprised patients presenting with mandibular
      fractures in the calendar years 1991 and 1992. A total of 147 fractures were seen
      in 96 patients, with the majority of patients being males in the age group 20-29
      years who sustained injury due to interpersonal assault. The pattern of injury
      was mostly unilateral due to low velocity impact and the site of the mandible
      that was most vulnerable to trauma was the angle of the mandible.

PMID- 8886872
TI  - Reasons for living and coping abilities among older adults.
AB  - Older adults have successfully resisted inclinations to commit suicide; however,
      little research has focused on their ability to cope or their reasons for living.
      In the present study, seventy-nine (fifty-five women, twenty-two men, two
      unknown) older adults (M = 60.6 years) recruited from churches, retirement groups
      (n = 22), and relatives of college psychology students (n = 57), completed the
      Reasons for Living and the Cope inventories. Overall coping was significantly
      positively correlated with total reasons for living, r(78) = .19, p < .05,
      although the low correlation suggests that the constructs are moderately unique.
      Further, coping was positively correlated with two RFL subscales, Survival and
      Coping Beliefs, r(78) = .27, p < .01, and Child-Related Concerns, r(78) = .28, p
      < .01. Women were higher than men in total reasons for living, t(75) = 2.16, p <
      .05, but not significantly different in coping abilities. Older women may
      underrate their ability to cope. An implication is that suicide prevention
      strategies should target men and bolster their cognitive deterrents to suicide.

PMID- 8886873
TI  - Risk factors associated with negative interactions between family caregivers and
      elderly care-receivers.
AB  - This article reports the findings from a study of factors related to negative
      interactions between elderly care-receivers, recently discharged from a hospital
      stay, and their family caregivers. Negative interactions are measured as over
      conflicts between the caregiver and care-receiver, and reported levels of upset
      with the caregiver. Respondents were forty-one patients aged fifty-six to ninety
      years. Feeling like a "thing" more than a "person" was significantly associated
      with higher levels of conflict, and the availability of a confidante was
      significantly associated with lower levels of conflict. With respect to upset
      ratings, more psychological distress and feeling like a "thing" were associated
      with more upset, and adequate social support, as well as the availability of a
      confidante were associated with lower upset ratings.

PMID- 8886874
TI  - Exploring the Caregiver Burden Inventory (CBI): further evidence for a
      multidimensional view of burden.
AB  - The purpose of this study was to examine the multidimensional nature of caregiver
      burden by specifically analyzing the patterns of association between five
      dimensions of burden as measured by the Caregiver Burden Inventory [1] and
      selected demographic, health, functioning, and well-being indicators. Subscales
      measuring each dimension were internally consistent and relatively independent in
      a sample of 160 caregivers. Time dependence burden was most influenced by patient
      impairment and caregiving involvement, whereas emotional burden was largely a
      function of caregiving satisfaction. Most of the variance in developmental burden
      was explained by depression and caregiving satisfaction. Contrary to
      expectations, physical health measures explained little variance in physical
      burden, of which most was explained by depression. Less than 10 percent of the
      variance in social burden was explained by depression and caregiver days sick.
      The findings lend support to a multidimensional view of burden and with minor
      modifications, the CBI appears to be a promising instrument with which to measure
      the construct.

PMID- 8886875
TI  - Interventions for caregivers of patients with Alzheimer's disease: a review and
      analysis of content, process, and outcomes.
AB  - Current reviews of the caregiver intervention literature have focused primarily
      on the outcomes of interventions for caregivers and general methodological
      limitations of individual studies (i.e., sampling and recruitment issues,
      adequacy of outcome measures, and generalization issues). Little attention has
      been paid to the specific factors affecting the therapeutic process, including
      the intensity and integrity of the interventions used. The purpose of this review
      is to examine closely the content and process of Alzheimer's disease (AD)
      caregiver interventions. We describe the types of interventions currently in use,
      factors affecting intervention outcomes, and we conclude with specific
      recommendations for the application of intervention technology and for the
      documentation of intervention research.

PMID- 8886876
TI  - Symposium: ovarian tumors of borderline malignancy.

PMID- 8886877
TI  - Ovarian neuroendocrine carcinomas of non-small-cell type associated with surface
      epithelial adenocarcinomas. A study of five cases and review of the literature.
AB  - Five primary ovarian carcinomas composed of a high-grade neuroendocrine tumor of
      non-small-cell type and a surface-epithelial-stromal tumor are reported. The five
      tumors presented in women aged 36 to 77 (mean, 57) years with abdominal
      distension or a palpable mass in three cases, right lower quadrant pain with
      tenderness and fever in one case, and a cervicovaginal smear showing a high
      estrogen effect in one postmenopausal patient. The tumors were unilateral, 9 to
      30 (mean, 16) cm in greatest dimension, and had solid and cystic components.
      Three tumors were stage I; one, stage II; and one, stage III. Two patients who
      received chemotherapy died of tumor 8 and 36 months postoperatively, another who
      refused chemotherapy but later received radiation died of tumor after 19 months,
      a fourth was lost to follow-up, and a fifth was treated recently.
      Microscopically, the neuroendocrine components of all the tumors were composed
      predominantly of sheets, closely packed islands, cords, and trabeculae of
      epithelial cells with little intervening stroma. The tumor cells in the
      neuroendocrine areas were medium-sized to large compared with the cells of small
      cell carcinoma, and they contained scanty to moderate amounts of cytoplasm and
      hyperchromatic nuclei with coarse chromatin clumping in three cases and abundant
      cytoplasm and vesicular nuclei with single, large eosinophilic nucleoli in the
      other two. In all the cases, areas of necrosis and single-cell necrosis were
      extensive, and mitotic figures were abundant. Positive argyrophil and argentaffin
      reactions were observed in occasional to many cells in all cases. The glandular
      components of the tumors were grade 1/3 endometrioid adenocarcinoma (one case),
      grade 2/3 mucinous adenocarcinoma (2 cases), and mucinous borderline tumor with
      small foci of mucinous adenocarcinoma (two cases). Numerous enterochromaffin
      cells were identified in hematoxylin and eosin sections of the borderline
      mucinous components of two tumors; occasional nonargentaffin argyrophilic cells
      were present in the endometrioid and mucinous carcinoma components. Luteinized
      stromal cells were present focally in two cases, including the case in which
      there was evidence of a high estrogen level. Immunohistochemical studies in five
      cases showed staining of most cells in the solid components for cytokeratin and
      chromogranin A and some to most cells for serotonin and neuron-specific enolase.
      Neuropeptides that were detected in the solid component of one or more of the
      cases included vasoactive intestinal peptide, somatostatin, gastrin, and
      glucagon; negative results were obtained for pancreatic polypeptide and insulin.
      Flow cytometry in four tumors revealed that the neuroendocrine component was
      aneuploid in two, suspicious for aneuploidy in one, and diploid in one. Tumors of
      the type described are distinct pathologically from primary ovarian carcinoid
      tumors and small cell carcinoma of pulmonary type. Although experience with this
      type of tumor is limited, the prognosis appears to be poor.

PMID- 8886878
TI  - Evaluation with MIB1 antibody of proliferative activity in ovarian clear cell
      adenocarcinoma.
AB  - The purpose of this study was to determine whether proliferative activity is a
      prognostic factor in ovarian clear cell adenocarcinoma. The paraffin-embedded
      sections from eight cases of ovarian clear cell adenocarcinoma were immunostained
      with monoclonal antibody MIB1 using microwave oven heating for antigen retrieval.
      The difference in survival (Kaplan-Meier) between patients with high and low MIB1
      expression was estimated with the generalized Wilcoxon test. MIB1 positivity
      ranged from 1.80 to 27.12% with a mean of 11.43%. A cutoff point of 10%
      dichotomized patients into two groups. The survival of high (> or = 10%)
      expressing tumors was worse than that of low (< 10%) expressing tumors (p <
      0.05). MIB1 immunostaining may have useful prognostic value in ovarian clear cell
      adenocarcinoma.

PMID- 8886879
TI  - Cytokine, cell adhesion receptor, and tumor suppressor gene expression in vulvar
      squamous carcinoma: correlation with prominent fibromyxoid stromal response.
AB  - In a previous report, we observed by light microscopy the extracellular matrix in
      51 vulvar squamous carcinomas and found that some tumors has a prominent stromal
      response in the form of a regional or diffuse zone of extracellular myxoid matrix
      containing immature collagen and fibroblasts at the tumor-stromal junction. These
      tumors were associated with clitoral involvement, ulcerative nonexophytic growth
      pattern, older age groups, poorer survival rate, and more extensive lymph node
      metastases than when prominent fibromyxoid stromal response (PFSR) was absent.
      This behavior was demonstrated despite the fact that these tumors were not
      larger, more deeply invasive, or of higher grade than when PFSR was absent. In
      the current immunohistochemical study, we examined cytokine, cell adhesion
      receptor, and tumor suppressor gene expression in 50 vulvar squamous carcinomas
      using a panel of antibodies to identify any potential role of these proteins in
      the development of a PFSR. Semiquantification of expression into none, focal (<
      25% of cells showing expression), regional (25-50%), and diffuse (> 50%) patterns
      revealed PFSR to be statistically associated with high CD44, transforming growth
      factor (TGF) beta 3, and p53 protein expression, but not with fibroblast growth
      factor, epidermal growth factor, epidermal growth factor receptor, or E-cadherin
      expression. When expression of CD44 and either stromal or tumor TGF-beta 3
      expression was high, i.e., regional or diffuse in distribution, 15 (50%) of 30
      cases were associated with PFSR. In contrast, only 1 (7%) of 14 cases was
      associated with PFSR when expression was high for only one of these two proteins
      and none of 3 cases was associated with response when expression was low for both
      proteins (p = 0.005). Furthermore, in cases showing high expression for both TGF
      beta 3 and CD44, PFSR was found in 13 (72%) of 18 cases when p53 expression was
      diffuse compared with 2 (17%) of 12 cases when expression was less (p = 0.01).
      Since TGF-beta acts mitogenically for fibroblasts and has been shown to be an
      inhibitor of epithelial cell growth, its high expression in a carcinoma with PFSR
      would suggest loss of effect on the epithelial component but an intact effect on
      the stroma. Since CD44 is known to act as a receptor for hyaluronic acid, which
      is a prominent stromal component and known to play an important role in cell
      mobility and tumor aggressiveness, its high expression in association with PFSR
      would suggest a role of CD44 overexpression in altered hyaluronate metabolism
      with accelerated tumor cell migration and subsequent distal spread. The current
      study demonstrates that alterations in cytokine and cell adhesion receptor status
      variably occur in vulvar squamous carcinoma and that such alterations may affect
      tumor morphology and behavior.

PMID- 8886880
TI  - Cytokeratin and vimentin expression in primary and recurrent carcinoma of the
      vulva: correlations with prognostic factors and the course of disease.
AB  - Radical vulvectomy for the treatment of a vulvar carcinoma inevitably entails
      severe psychosexual consequences for the patients. Thus, for such tumors,
      reliable histological prognostic parameters are needed to allow; when
      appropriate, the use of less radical operative measures. One possible approach to
      this problem might be to examine tumors immunohistochemically for the presence of
      cytoskeletal components. To assess the utility of this method, we applied a panel
      of antibodies directed against cytokeratins (CKs) and vimentin to a groups of
      vulvar carcinomas (62 primary and 35 recurrent tumors) and examined the results
      for possible correlations with the course of disease and various clinical
      parameters. all of the investigated CKs typical of squamous epithelia had no
      prognostic relevance. In contrast, the present of CKs typical of glandular
      differentiation as well as vimentin, suggesting early dedifferentiation, resulted
      in a less favorable prognosis. Thus, the procedures applied in the present study
      may have a role to play a decisions concerning the appropriate therapy for such
      tumors.

PMID- 8886881
TI  - Epithelial repair of the uterine cervix: assessment of morphologic features and
      correlations with cytologic diagnosis.
AB  - This study evaluates the morphologic features of squamous epithelial repair of
      the uterine cervix, a condition describing a state of regeneration, and compares
      them with the features of its two histologic mimics, squamous metaplasia and mild
      dysplasia. The materials examined were from 20 patients with a histologic
      diagnosis of repair, 42 with cervical biopsy specimens of acceptable quality
      obtained within 3 weeks of a cervical smear showing repair, and 20 each with
      squamous metaplasia or mild dysplasia. Specimens with repair disclosed
      distinctive morphologic characteristics. On low-power magnification, the stroma
      was chronically inflamed (100%), often floridly (55%). The nuclei were uniform
      with absent or minimal pleomorphism (90%). The chromatin was bland and evenly
      distributed (70%). Nucleoli of a bull's eye or macronucleolar appearance (45%)
      were easily found. Mildly dysplastic epithelium, unlike reparative epithelium,
      was infrequently associated with an intensely inflamed stroma (20%); its nuclei
      were pleomorphic (100%) and commonly displayed coarse chromatin (75%) and mitoses
      (60%). Metaplastic epithelium ws also infrequently associated with an intensely
      inflamed stroma (10%). Nuclear pleomorphism (10%) and mitotic figures were
      infrequent (10%), never atypical (0%), and always basally located. Most nuclei
      had nucleoli, but the majority were small (80%). This study indicates that most
      cases of repair, mild dysplasia, and metaplasia can be readily distinguished,
      although due to overlapping features, some cases are difficult to classify as
      shown by interobserver variability.

PMID- 8886882
TI  - Estrogen and progesterone receptor expression in endometrial polyps.
AB  - Endometrial polyps are a frequent cause of abnormal uterine bleeding, but their
      pathogenesis is poorly understood. This study was undertaken to investigate if
      endometrial polyps result from localized overexpression of estrogen receptors
      (ERs) or reduced expression of progesterone receptors (PRs). Fourteen cases of
      endometrial polyps, in which normal cycling endometrium was also present on the
      same slide, were immunostained for ERs and PRs. Percentages of positive cells in
      glands and stroma for each receptor were subjectively assessed to the nearest 5%.
      The intensity of staining was recorded on a scale from 1+ to 4+. The level and
      intensity of staining in polyps were compared with the staining in normal
      endometrium. Fewer stromal cells in polyps expressed ERs and PRs compared with
      cycling endometrium (% ER = 55.9 +/- 25.8 vs. 74.3 +/- 25.8, p = 0.03; % PR =
      56.1 +/- 28.2 vs. 87.5 +/- 10.1, p = 0.002). Stroma in polyps also had
      significantly reduced intensity of staining for PRs, but not for ERs (intensity
      PR = 2.7 +/- 1.4 vs. 3.5 +/- 0.7, p = 0.015; intensity ER = 2.1 +/- 0.7 vs. 2.4
      +/- 0.8, p = 0.45). There were no significant differences in expression of ERs
      and PRs in the endometrial glands in endometrial polyps compared with normal
      endometrium (% ER = 75.4 +/- 32.5 vs. 70.7 +/- 39.2. p = 0.25; % PR = 79.6 +/-
      32.8 vs. 80.4 +/- 34.4, p = 0.8; intensity ER = 2.7 +/- 0.9 vs. 2.4 +/- 1, p =
      0.15; intensity PR = 2.9 +/- 1.4 vs. 3.4 +/- 0.7, p = 0.15). We conclude that
      endometrial polyps may result from a decrease in ER and PR expression in stromal
      cells. Because of these receptor-negative stromal cells, endometrial polyps may
      be relatively insensitive to cyclic hormonal changes.

PMID- 8886883
TI  - Adenoid cystic carcinoma of the submandibular gland with symptomatic ovarian
      metastases.
AB  - We report the clinical and pathologic features of an adenoid cystic carcinoma of
      the submandibular gland that metastasized to the ovaries 10 years after initial
      presentation. A 30-year-old woman underwent excision of a right submandibular
      adenoid cystic carcinoma followed by regional external beam radiation therapy.
      Three years later, she underwent extended hepatic resection and localized
      radiotherapy to the hepatic region for metastatic disease. The patient was
      without evidence of disease for 7 years when she developed pelvic pain and a
      pelvic mass was found. A solid and cystic 10-cm left ovarian mass and a single
      metastatic tumor nodule involving the right ovary were excised via the
      laparoscope. Histologically, the tumor was identical to the patient's initial
      salivary gland neoplasm. The neoplastic cells were CAM 5.2 positive, S100
      positive, muscle-specific actin positive, and smooth muscle actin positive.
      Ultrastructurally, characteristic pseudocysts (pseudolumina) with abundant basal
      lamina and true glandular lumina lined by short microvilli were present. Other
      than a single anecdotal account of a parotid gland adenoid cystic carcinoma, this
      case represents the first documented report of an adenoid cystic carcinoma of
      salivary gland origin that was associated with symptomatic ovarian metastases.
      This case demonstrates that the ovary is a potential site for metastatic disease
      many years following the diagnosis and treatment for a primary neoplasm however
      uncommon or remote the site of origin. Since metastatic adenoid cystic carcinoma
      can rarely present as an ovarian mass, a clinical history of this neoplasm should
      be heavily weighed in the differential diagnosis of any unusual ovarian tumor
      with a predominant cribriform, trabecular, or tubular pattern.

PMID- 8886884
TI  - Malignant melanoma arising in mature ovarian cystic teratoma (dermoid cyst).
      Report of two cases and literature analysis.
AB  - Malignant melanoma may originate from melanocytes in ovarian cystic teratomas
      (dermoid cysts). Two cases are reported here and an additional 17 cases are found
      in a literature review covering 1903-1995. The review also found cases of benign
      and malignant melanotic ovarian lesion unassociated with dermoid cyst, including
      four melanomas, three cases of benign nevus, five cases of benign melanosis, and
      four cases of benign and malignant retinal anlage tumors. The extremely rare
      primary ovarian melanoma may be differentiated from the more common melanoma
      metastatic to the ovaries by its unilaterality, the presence of junctional
      change, and a detailed history and physical examination to exclude another
      primary site. Overall, 50% of patients with Stage I dermoid-associated melanoma
      were alive at 2 years compared with 89% of patients with Stage I dermoid
      associated squamous carcinoma at 5 years. In the last 10 years, however, with the
      application o aggressive chemotherapy, survival has improved.

PMID- 8886885
TI  - Acute monocytic leukemia (FAB M5) involving the placenta associated with delivery
      of a healthy infant: case report and discussion.
AB  - Acute leukemia seldom presents during pregnancy, and though pregnancy may not
      affect the course of leukemia, fetal complications and maternal mortality are
      high. Documented placental involvement is rare, as are metastases to the fetus.
      Comprehensive review of the literature reveals only a few reports of maternal or
      fetal leukemia with placental involvement. We encountered a case of a 45-year-old
      woman who presented at 29 weeks' gestation with acute monocytic leukemia with
      t(9;11). She was managed conservatively. Labor was induced at 33 weeks, with
      delivery of a healthy male infant prior to induction chemotherapy. The baby
      remained well at 18 months of age. The placenta showed isolated microinfarcts and
      an infiltrate in the basal plate of leukemic cells confirmed by
      immunohistochemistry. No invasion into chorionic villi was seen. Little is known
      about the biological significance of placental involvement and inherent defense
      mechanisms of the placenta in maternal cancers. Therefore, detailed
      histopathologic examination of the placenta should always be performed and
      reported in leukemic patients, regardless of fetal outcome.

PMID- 8886886
TI  - Initial in vivo experience with EIT as a thermal estimator during hyperthermia.
AB  - Thermal imaging experiments using electrical impedance tomography (EIT) have been
      conducted during hyperthermia treatments delivered to two human patients and one
      animal subject. Coplanar and circumferential arrays of 16 and 32 tin-plated
      copper electrodes etched on a 0.005" polyimide sheet were used to inject 12.5 KHz
      current patterns of increasing sinusoidal spatial frequencies and subsequent
      potential distributions were recorded at each electrode site. Image
      reconstruction was achieved with a finite element method and difference images of
      conductivity changes during the course of treatment were formed. An assumed
      linear relationship (2%/degree C increase) between tissue impedance change and
      temperature change was used to produce thermal images of the treatment field in
      patients whereas an empirically measured nonlinear relationship obtained from
      excised tissue samples was applied retrospectively in the animal subject case.
      Reconstructed conductivity changes are shown to be possible given electrical data
      measured in vivo during hyperthermia delivery with conventional equipment (spiral
      microstrip applicator at 433 MHz). These correlated well with direct temperature
      measurements and demonstrated quantitative levels of agreement to the extent that
      estimated temperature accuracies were approximately 1.5 degrees C; although large
      errors (> 5 degrees C) did exist. This work suggests that EIT is a potentially
      useful tool for hyperthermia treatment monitoring and assessment. The
      relationship between tissue impedance and temperature is complex and confounds
      the ability to make simple correlations between conductivity and temperature
      changes. Further, study is required to discern whether this will ultimately limit
      EIT as a thermal estimator or whether it will lead to more fundamental uses of
      impedance as an indicator of thermal effect.

PMID- 8886887
TI  - Transurethral hyperthermia for benign prostatic hyperplasia: long term results.
AB  - Transurethral resection of the prostate (TURP) is the only recognized treatment
      in patients with benign prostatic hyperplasia (BPH). Transurethral hyperthermia
      (TUHT) was used as an alternative treatment in patient who refused TURP. From
      1987 to 1988, 21 BPH patients with moderate to severe symptoms and signs of
      prostatism were treated with TUHT in a phase I trial. Mean pre-treatment
      subjective and objective values were: total symptom score (TSS) 13.5, obstructive
      symptom score (OSS) 6.5, irritative symptom score (TSS) 7.0, peak flow rate (PFR)
      11.6 cc/sec, post-voiding residual volume (PRV) 187 cc, and prostate volume (PV)
      93 cc. TUHT was given for a total of 177 sessions (mean 8.4), each of 60 min
      duration at a steady state. Temperature was recorded continuously on the urethral
      surface, in all treatments. It ranged from Tmin 40.3 degrees C to Tmax = 49.2
      degrees C and Tmean = 44.1 degrees C. The mean minimum temperature of > or = 42
      degrees C was obtained in 98% of the TUHT sessions. Treatments were given on an
      outpatient basis without sedation or anaesthesia. Treatment tolerance was
      excellent with minor acute toxicity common (71% of patients), of no clinical
      importance and with no late complications. Of the 21 patients treated, 17 (81%)
      had an objective and 15 (71%) a subjective improvement recorded at 6 months post
      treatment. This statistically highly significant improvement included: 61%
      decrease in TSS; 66% decrease in OSS; 55% decrease in ISS; 42% increase in PFR;
      55% decrease in PRV; and 21% decrease in PV. Of the 17 patients with objective
      improvement, nine have maintained their response to TUHT for a minimum period of
      over six years, two relapsed at 11 and 40 months, respectively, and six patients
      died of cardiovascular causes maintaining their response to death. This study has
      demonstrated TUHT treatment efficacy with no major or clinically important
      toxicity in BPH patients. A relative weakness of this report is a lack of
      verification of objective study parameters in the patients at seven years post
      treatment. Prospective randomized trials are needed to define the role of TUHT in
      the management of BPH patients.

PMID- 8886888
TI  - TNF-alpha and endotoxin serum levels in cancer patients undergoing
      intraperitoneal hyperthermic perfusion.
AB  - Intraperitoneal hyperthermic perfusion (IPHP) is performed as one treatment for
      patients with advanced gastrointestinal cancer complicated by peritoneal
      dissemination or carcinomatous peritonitis. However, the anticancer mechanism of
      IPHP and its safety have not yet been fully elucidated. It has been
      experimentally known that endotoxinemia occurs by high body temperature, and that
      endotoxin stimulates the macrophage, monocyte and endothelial cell to induce the
      production of TNF-alpha. TNF-alpha is one of cytokines to be induced at the
      initial phase as a host immune response and play an important role to initiate
      the systemic inflammatory response syndrome (SIRS). We have tested whether the
      serum concentrations of TNF-alpha and endotoxin are elevated following IPHP.
      Eleven patients with gastro-intestinal cancer underwent surgery combined with
      IPHP. Mixed venous blood obtained from pulmonary artery (PA-blood) was collected
      at four sampling points. TNF-alpha and endotoxin levels in the PA-blood were
      measured by ELISA and a limulus amoebocyte lysate assay respectively. In all
      patients the serum TNF-alpha levels in PA-blood were temporarily elevated
      following IPHP from less than 10 pg/ml before IPHP to 42.8 +/- 26.6 pg/ml;
      endotoxin levels were not altered. This study shows that IPHP has the ability to
      induce endogenous TNF-alpha not mediated by endotoxin.

PMID- 8886889
TI  - Protective effect of NG-monomethyl-L-arginine against hypotension inducted by
      combined tumour necrosis factor-alpha and whole body hyperthermia in rats.
AB  - We studied: (a) the adverse effects of tumour necrosis factor-alpha (TNF) given
      during whole body hyperthermia (WBH) on mean arterial pressure (MAP) and gut
      mucosa in anaesthetized rats; (b) the potential protective effect of NG
      monomethyl-L-arginine (L-NMA), an inhibitor of nitric oxide synthase; and (c) the
      influence of L-NMA on the antitumour effect of the trimodality therapy, WBH + TNF
      + Carboplatin (CBDCA). In normothermic rats, TNF alone (10(5) or 10(6) U/kg) did
      not cause hypotension, but increased MAP (p < 0.05). L-NMA alone (5, 10 and 20
      mg/kg) increased MAP moderately and dose-dependently (p < 0.05). WBH (41.5
      degrees C for 2 h) increased MAP markedly (from 103 +/- 4 to 161 +/- 4 mm Hg).
      This increase in MAP was sustained throughout the hyperthermia, but was followed
      by a transient relative hypotension (MAP = 80 +/- mm Hg) on cessation of WBH and
      an eventual return to near baseline at 30 min post-WBH (MAP = 94 +/- 5 mm Hg).
      WBH + TNF (10(5) or 10(6) U/kg) initially increased MAP similarly to WBH alone.
      During the second hour of WBH, however, MAP decreased towards pre-treatment
      levels, and cessation of WBH was followed by sustained hypotension. This late
      hypotensive state was associated with a mortality during the early (first 2 h)
      post-WBH period of 17 and 100% at TNF dose of 10(5) and 10(6) U/kg TNF,
      respectively. L-NMA given to rats receiving WBH + TNF (10(6) U/kg) maintained MAP
      at levels similar to WBH alone during WBH treatment. L-NMA prevented the post-WBH
      hypotension, and extended the survival beyond the early (first 2 h) post-WBH
      period. No rat, however, receiving high dose TNF (10(6) U/kg) survived more than
      12 h even with L-NMA (totally 40 mg/kg). WBH + TNF (10(5) and 10(6) U/kg) also
      produced marked histopathological injury to the gut mucosa at 2 h post-treatment.
      L-NMA substantially protected the gut from this injury. In rats bearing a
      transplantable fibrosarcoma, L-NMA did not decrease the antitumour effect
      consisting of WBH + TNF (10(5) U/kg) + CBDCA, while it decreased (p < 0.05) the
      general toxicity (weight loss, diarrhea and foot oedema) of this combination. We
      conclude that L-NMA may prevent or ameliorate the early toxicity but not the late
      lethal effects of WBH + high dose TNF (10(6) U/kg). Additionally, L-NMA reduces
      some of the toxicity of WBH + TNF (10(5) U/kg) + CBDCA without decreasing the
      antitumour effect of this trimodality therapy. Inhibitors of nitric oxide
      synthase such as L-NMA may provide a novel approach to overcoming the toxicity of
      TNF in combination with WBH.

PMID- 8886890
TI  - Increased tumour response of a murine fibrosarcoma to low temperature
      hyperthermia and low dose rate brachytherapy.
AB  - The present animal tumour study was carried out to determine the effectiveness of
      low temperature hyperthermia combined with low dose rate radiation based on the
      cell culture studies of our laboratory and others that demonstrated a significant
      radiosensitization obtained by low temperature hyperthermia and low dose rate
      radiation. Well-oxygenated murine fibrosarcoma Meth-A tumours growing in Balb/c
      mice were treated with heat (41 degrees C tumour temperature) by immersion of the
      tumour-bearing leg in a waterbath concurrently with low dose rate radiation.
      Radiation was delivered using 192Ir interstitial implantation at absolute dose
      rates of 0.416-0.542 Gy/h. The effect of heat alone on tumour growth and normal
      tissue was minimal. Tumour growth delay following 30 Gy radiation was 4.9 days.
      Significant delay in tumour growth was observed with the addition of low
      temperature hyperthermia delivered concurrently. Enhancement in radiation
      response was seen with increasing duration of heat treatment; tumour growth
      delays were 9.5 days following 4 h heat (41 degrees C) treatment and 16 days
      following 6 h treatment. Three sessions of fractionated hyperthermia 4 h/day
      during the course of low dose-rate radiation significantly delayed tumour growth
      to 18.6 days. The results indicate that fractionated heat treatment in
      conjunction with low dose rate radiation has potential for improving tumour
      response without adversely affecting normal tissue reaction. This in vivo study
      represents an extension of the cell culture data and provides further
      radiobiological basis for the combined use of low temperature hyperthermia and
      low dose rate radiation.

PMID- 8886891
TI  - Chronic thermotolerance with continued cell proliferation.
AB  - The human colon adenocarcinoma cell line, NSY42129, is capable of proliferation
      at 41.1 degrees C. This ability appears to be due to a type of chronic
      thermotolerance, as opposed to selection or adaptation, that allows these cells
      to traverse S phase at elevated temperatures. Four other human cell lines were
      studied for their ability to proliferate at 41.1 degrees C. Of those only one,
      also a colon adenocarcinoma, showed the ability to sustain proliferation at 41.1
      degrees C. While all the cell lines examined showed increased levels of the major
      heat shock proteins at 41.1 degrees C, the cellular amounts of these proteins did
      not correlate with their ability to proliferate at 41.1 degrees C. However, the
      ability of the cells to proliferate at 41.1 degrees C did correlate with their
      ability to sustain elevated rates of synthesis of hsp70 and hsp90. These results
      could have implications in the clinical application of hyperthermia, particularly
      the use of long duration moderate hyperthermia.

PMID- 8886892
TI  - Sequence of treatment is important in the modification of camptothecin induced
      cell killing by hyperthermia.
AB  - We investigated the modification of camptothecin (CPT)-induced cell killing by
      hyperthermia in a radioresistant human melanoma (Sk-Mel-3) and a human normal
      (AG1522) cell line. CPT, a topoisomerase (topo) I inhibitor, was given as a 1 h
      exposure at variable doses up to 34 microM; hyperthermia was given either before
      or following CPT treatment. Hyperthermia was given either as a treatment of 41
      degrees C for 8 h (termed lower temperature hyperthermia, LTH) or 45 degrees C
      for 15 min (termed higher temperature hyperthermia, HTH). LTH preceding CPT
      treatment had no effect on Sk-Mel-3 but potentiated killing of AG1522 cells. HTH
      preceding CPT treatment, however, almost completely abrogated the toxicity of CPT
      to both Sk-Mel-3 and AG1522 cells. These results therefore provided evidence for
      a lack of enhancement of CPT toxicity towards Sk-Mel-3 cells when hyperthermia
      preceded treatment with CPT. There was also no potentiation of killing of both
      cell lines when LTH followed treatment with CPT. In contrast, the killing of Sk
      Mel-3 cells was slightly potentiated, whereas that of AG1522 cells was reduced,
      when HTH followed CPT. These results therefore suggested a potential for
      enhancement of killing of Sk-Mel-3 relative to AG1522 cells when HTH, but not
      LTH, followed CPT treatment. In addition, we found that a preceding exposure ot
      HTH did not affect either accumulation or efflux of[3H]CPT in both cell lines.
      Thus the significantly reduced cytotoxicity observed under those conditions was
      not related simply to a modification of accumulation or efflux of CPT. We found
      no significant differences in the atalytic activities of topo I extracted from
      the nuclei of Sk-Mel-3 and AG1522 cells that were either heated under HTH
      conditions or that were no subjected to such treatment. These results therefore
      suggested that the substantial reduction of cytotoxicity seen when HTH preceded
      CPT treatment was also not due to an effect on topo I catalytic activity. Our
      results therefore demonstrate that the sequence of application of hyperthermia
      and CPT is very important in determining the amount and, possibly, selective
      potentiation of tumour relative to normal cell cytotoxicity.

PMID- 8886893
TI  - Heat shock causes protein aggregation and reduced protein solubility at the
      centrosome and other cytoplasmic locations.
AB  - Heat shock markedly inhibited centrosome staining by antisera raised against the
      two centrosome-specific proteins, pericentrin and gamma tubulin. The inhibition
      of anti-pericentrin binding was measured by fluorescence imaging. Heat had the
      greatest effect on intact cells, followed in sensitivity by centrosomes attached
      to their companion nucleus, with purified centrosomes being least sensitive. The
      centrosomal content of pericentrin was measured by immunoprecipitation followed
      by western blotting. Heat caused the amount of pericentrin in the centrosomal
      fraction to increase, suggesting that pericentrin did not leave the centrosome
      during heat shock. Furthermore, the pericentrin of the centrosomal fraction
      became less soluble after heat shock, and could only be solubilized by the most
      denaturing condition of boiling in 0.1% SDS. Immunoelectron microscopy revealed a
      heat-induced increase in the electron-dense material comprising the
      pericentriolar material (PCM), consistent with protein aggregation. Lastly, in
      heated cells immunoelectron microscopy demonstrated an increase in the binding of
      heat shock protein 70 (HSP70) to numerous locations throughout the cytoplasm.
      These data suggest that heat shock reduces the solubility of centrosomal and
      other cytoplasmic proteins, most likely through protein aggregation.

PMID- 8886894
TI  - Cell line from a primary culture of human colon carcinoma.

PMID- 8886895
TI  - Time-temperature parameters and scheduling protocols.

PMID- 8886896
TI  - Cultural discourse and the myth of stress in nursing and medicine.
AB  - Nursing has within the last 20 years firmly embraced the idea that practice
      should be based on substantive research. Yet many of the issues with which modern
      nursing is grappling encompass complex multifaceted aspects which are difficult
      to conceptualise or define. Stress is one such concept which has been
      increasingly invoked in both health care and lay discourses as an explanation for
      illness and general misfortune. A number of models of stress have been proposed
      which have to a greater, or lesser extent also been adopted by the lay public. In
      many respects nursing models of health and illness have more in common with lay,
      rather than biomedical, conceptualisations of illness aetiology. However, it is
      unclear to what extent nursing, lay and biomedical ideas about stress overlap.
      This paper attempts to explore some of these issues by describing the semantic
      origins of stress and the ways in which it is conceptualised and invoked in both
      the professional and lay discourse. The many approaches to stress research are
      explored and some of the constraints pertaining to them discussed. The question
      is also raised as to why certain discourses on stress have arisen within
      particular professional domains, and why the nursing contribution to stress
      research has been marginalised. An ideological component to the stress discourse
      is identified, and the importance of nursing and other professional disciplines
      recognising this, and also those macro-level factors which may affect health and
      illness, is stressed.

PMID- 8886897
TI  - Indicators of quality in long-term care facilities.
AB  - Quality of care is of particular importance to residents of long-term care
      facilities because of the permanency of their situation. In this study indicators
      of quality of care were generated from data obtained at a primary level from
      those most affected by the care. The critical incident technique was used to
      identify the indicators as perceived by 52 residents, 58 significant others, and
      37 nursing staff in five long-term care facilities in Calgary, Canada. The 14
      major indicators so identified are discussed in this paper.

PMID- 8886898
TI  - Expectations in giving and receiving help among nurses and Russian refugees.
AB  - Stimulated by the emergence of a new refugee group that is unknown and vulnerable
      to misunderstanding by health care providers, and the exigency in nursing to
      understand potential variance in nurse and client assumptions about helping, this
      paper reports exploratory research comparing helping orientations of Russian
      Protestant Pentecostal refugees (N = 28) with professional nurses (N = 32) in the
      United States. Findings based on the Brickman et al. (1982) theory of helping,
      which addresses attribution of responsibility in helping interactions, indicated
      differences among the nurse and Russian orientations. Contrasting with the
      nurses' primary selection of the moral orientation, which assumes high individual
      responsibility for the causes and solutions of problems, the Russian refugee
      group's first selection was the medical orientation, which assumes low individual
      responsibility for the causes and solutions of problems. The two groups'
      differing orientations are considered in the context of nurse-client interactions
      and divergent cultural values bearing on assumptions of individual
      responsibility.

PMID- 8886899
TI  - Nurses' memory of patient's pain.
AB  - This descriptive study examined the relationship between nurses' memory of
      patient's pain and patient stereotyping. The patient vignette information
      recalled by 148 nurses was content analyzed for accurate items, accurate
      analgesic items, and how accurately the patient's pain was recalled. Stereotyping
      was measured by z-scores for time planned for pain assessment and analgesic
      administration. No significant relationship was supported between memory and
      stereotyping. Nurses either recalled the patient's pain accurately (n = 58),
      inaccurately (n = 18), or completely omitted (n = 70) this information. Further
      study is needed to explore why nurses recalled the patient's pain differently,
      and how this might impact pain relief efforts.

PMID- 8886900
TI  - The work of auxiliary nurses in Mexico: stressors, satisfiers and coping
      strategies.
AB  - Recruitment and retention of nursing personnel is a major problem in many parts
      of the world, particularly developing countries. Strategies for promoting job
      satisfaction can help reduce the costs of high turnover and increase the quality
      of patient care. As part of a larger international study on women's health, a
      convenience sample of 59 Mexican nursing assistants and technical nurses,
      categorized as auxiliary nurses, were asked to complete a questionnaire designed
      to elicit their perceived work-related stresses and satisfactions, as well as the
      coping strategies they utilized to diminish work-associated stress. Major
      satisfiers included self-fulfillment, providing service and working as a member
      of a team. Frequent stressors were interpersonal relations, "angustia" (anguish),
      work overload and the work environment. These auxiliary nursing personnel
      utilized problem-solving techniques, recreational activities, talking to family
      and friends and actively trying to relax themselves in order to cope with their
      work-related stress.

PMID- 8886901
TI  - Key influences on the professional socialisation and practice of students
      undertaking different pre-registration nurse education programmes in the United
      Kingdom.
AB  - A principal aim of pre-registration nurse education programmes is the process of
      effective socialisation of students into the professional role. Key influences on
      the professional socialisation and practice of students undertaking such
      programmes were explored using a semi-structured interview approach (N = 99).
      This work formed part of a major comparative study of outcomes of pre
      registration nurse education programmes in the United Kingdom. Analysis revealed
      differences between the programmes regarding positive influences of the
      respective courses; therapeutic influences of the practice environment; modelling
      performance on exemplars of high quality practice; and the identification of
      teachers within the educational setting and nurses in practice as key persons.
      This study has confirmed that the positive influence of the education programmes
      and the practice environment as well as high quality role models from both
      education and practice establishments are critical to the professional
      socialisation of student nurses.

PMID- 8886902
TI  - Fatigue: a concept analysis.
AB  - Fatigue is probably the most common symptom of illness affecting sufferers of
      both acute and chronic conditions. However, confusion surrounds the definition
      and use of the term fatigue. As with many other nursing concepts, it is a word
      that is commonly used in colloquial language. This concept analysis aims to
      identify the attributes that are essential to the concept of fatigue, and to
      distinguish between its colloquial and its nursing usage by following the
      strategy suggested by Walker and Avant (1995, Strategies for Theory Construction
      in Nursing, Appleton Lange, London). A review of the literature identifies
      nursing uses of the term fatigue which reflect and conflict with colloquial uses.
      Defining attributes, demonstration cases, antecedents, consequences and empirical
      referents are identified before a definition of fatigue is developed and proposed
      for nursing. This clarification of the phenomenon has particular relevance for
      clinical nursing, future research and the development of fatigue theories.

PMID- 8886903
TI  - Comparative distribution and use of humour within nurse-patient communication.
AB  - There has been increasing interest in the use of humour in patient care within
      recent years. However, little research has been conducted to show the natural
      utilisation of humour, particularly from the participants' perspective, within
      the clinical environment. This study uses ethnomethodological ethnography and
      conversation analysis methods to investigate the use of humour between nurses and
      patients with renal failure who were learning about, and to, haemodialyse. It is
      believed that the project is unique in the utilisation of audiovisual video
      recordings to measure and describe the frequency, distribution and use of humour.
      Findings indicated that humour rates and the proportion of humour produced by the
      patients were differentially distributed between patients but, overall, not
      between the same patients on different occasions. In addition, in one case a
      significant positive relationship between the rate of humorous instances per
      session and time was demonstrated and another patient (D) was found to produce a
      significantly larger proportion of the humour over time. Further exploration of
      patient D's increasing use of humour revealed that one important aspect was
      associated with the patients anxiety and difficulties with regard to "needling'.
      The findings have implications for understanding the role of humour in health
      care communication, particularly with reference to developing formal "humorous
      interventions'.

PMID- 8886904
TI  - Emotional distress in men with life-threatening illness.
AB  - This descriptive survey explored the relationship of health status, functional
      status, stressful life events, stress resistance resources and emotional distress
      in 60 men with life-threatening illness (N = 30 with cancer and N = 30 with
      AIDS). Sixty-two percent met CES-D criteria for clinical depression. This study's
      results supported the hypotheses that poorer functional status and greater
      negative stressors are associated with both higher levels of hopelessness and
      depression. Twenty-four patients constituted a group with severe emotional
      distress. This group was significantly different from the less vulnerable group
      with poorer functional status (KPS), a greater number and severity of negative
      stressors, less satisfaction with social support, and less hopefulness.

PMID- 8886905
TI  - Continuing pain education in nursing: a literature review.
AB  - Twelve studies on the effects of pain programmes for nurses were reviewed. Most
      of the programmes focused on aspects of pain, pain medication or pain assessment.
      Only two programmes (Ferrell et al., 1993, J. Pain Symptom Management, Vol. 8,
      No. 8, pp. 549-556; Sofaer, 1983, Nurs. Times, Vol. 79, No. 47, pp. 38-42; 1984,
      Ph.D. Thesis, University of Edinburgh) also paid attention to non-pharmacological
      nursing interventions. Randomized control groups, established measurement
      instruments, testing statistics, and long-term follow-up measurements, were not
      often used in the effect evaluation of the programmes. Effects reported on both
      nurses and patients were for the most part positive. Given the small number of
      studies and their methodological limitations, further research into the
      effectiveness of continuing pain education in nursing is indicated.

PMID- 8886906
TI  - Intravesical therapy of bladder cancer: an immunotherapy success story.

PMID- 8886907
TI  - Management of late complications of continent urinary diversion using the Kock
      pouch and the Indiana pouch procedures.
AB  - BACKGROUND: Continent urinary diversion (CUD) is performed on patients after
      total cystourethrectomy due to invasive bladder cancer or other diseases
      requiring urinary diversion. Since 1984, we have performed CUD using either the
      Kock pouch procedure or a modified Indiana pouch method. During the long-term
      follow-up, increasing numbers of late complications occurred, especially after
      the Kock pouch procedure. We summarized the frequency of postoperative
      complications, their management, and outcome of CUD using these 2 methods.
      METHODS: Between 1984 and 1995, CUD using the Kock pouch method was performed on
      102 patients, and on 61 patients using the Indiana pouch method, with a mean
      follow-up period of 83 and 50 months, respectively. The patients were between 24
      and 82 years old, with a mean age of 59 years. In most patients, the Kock pouch
      was constructed according to the original method, except for the use of a Dacron
      fabric collar, and the Indiana pouch was made using the ileal patch method.
      RESULTS: Of 95 patients followed up for more than 3 months after CUD using the
      Kock pouch method, efferent and afferent nipple valve malfunction occurred in 21
      (22%) and 26 (27%) patients, respectively. Efferent complications occurred during
      the first year after surgery, whereas afferent complications occurred several
      years after surgery. Open repair surgery (excluding ileus) was necessary for 36
      (38%) patients. Of 59 patients followed for more than 3 months after CUD using
      the Indiana pouch method, 7 patients with stomal stenosis, 2 patients with stomal
      prolapse, and 1 patient with stricture at the ureterocolonic anastomosis were
      treated surgically. An hourglass-like deformity of the pouch was seen in 2
      patients, on whom the original Indiana pouch method was performed. As a whole, 13
      patients (22%) were retreated with open surgery. Urinary calculi occurred in 42
      (44%) patients after CUD using the Kock pouch method and in 11 patients (19%)
      using the Indiana pouch method. The outcome was excellent, good, fair, and poor
      in 31, 37, 24, and 8% of the patients after CUD using the Kock pouch method, and
      in 36, 17, 42, and 5% of the patients after CUD using the Indiana pouch method.
      CONCLUSIONS: We performed CUD using either the Kock pouch or the Indiana pouch
      method with a success rate of approximately 90%. The rates of revision,
      reoperation and stone formation were higher with the Kock pouch procedure than
      with the Indiana pouch procedure, while varying degrees of incomplete
      incontinence and difficulty in catheterization were seen more often in the
      latter.

PMID- 8886908
TI  - Serum interleukin-6 levels after urologic operations.
AB  - BACKGROUND: Endourology, extracorporeal shock wave lithotripsy (ESWL), and
      laparoscopic surgery are considered minimally invasive procedures; however,
      estimation of operative invasiveness has not been fully accomplished. We measured
      serum interleukin-6 (IL-6) levels, as an indicator for systemic reaction, to
      examine operative invasiveness of these operations in comparison with open
      surgery. METHOD: Serum IL-6 levels were measured in 119 patients undergoing open
      surgery, laparoscopic surgery, endourology, and ESWL. RESULTS: The median IL-6
      levels on day 1 after the operation varied according to operative procedures:
      83.5 pg/mL (range, 15-340 pg/mL) for open surgery, 24.8 pg/mL (range, 12-42
      pg/mL) for laparoscopic surgery, and 10.8 pg/mL (range, 0-85 pg/mL) for
      endourology and ESWL. The extent of tissue injury and blood loss were found to be
      2 major factors responsible for the serum IL-6 elevation. CONCLUSION: The
      minimally invasive character of endourology, ESWL, and laparoscopic surgery is
      attributable to low levels of tissue injury and blood loss, regardless of
      operative time.

PMID- 8886909
TI  - The protective effect of methylprednisolone against cisplatin-induced
      nephrotoxicity in patients with urothelial tumors.
AB  - BACKGROUND: Many attempts have been made to reduce the nephrotoxicity of the
      anticancer agent cisplatin but the number of clinically useful modalities is very
      limited. Our previous experiments demonstrated that in rats methylprednisolone
      significantly reduces the nephrotoxicity caused by cisplatin. The present
      clinical study was conducted to confirm the protective effects of
      methylprednisolone against cisplatin nephrotoxicity. METHODS: Fourteen patients
      with urothelial tumors were injected with cisplatin according to the
      methotrexate, vinblastine, adriamycin, cisplatin (MVAC) therapy.
      Methylprednisolone was not administered during the first course of chemotherapy
      to provide a control, but was given in a dose of 2000 mg 2-3 hours before
      cisplatin during the second course of chemotherapy (treatment period) in each
      patient. Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma
      glutamyltranspeptidase (GGTP), serum creatinine, and creatinine clearance (Ccr)
      were determined as indicators of the nephrotoxicity of cisplatin. Results were
      statistically analyzed by a paired t test to compare the nephrotoxic effects of
      cisplatin during the first course of chemotherapy (control period) with those
      during the second course of chemotherapy (treatment period). RESULTS:
      Methylprednisolone did not significantly inhibit the elevation in urinary enzyme
      excretion or serum creatinine levels following the cisplatin injection. However,
      the Ccr level after cisplatin infusion in the treatment period was significantly
      higher than that observed in the control period. CONCLUSION: The protective
      effects of methylprednisolone against cisplatin nephrotoxicity were indicated in
      this prospective clinical study.

PMID- 8886910
TI  - Pyeloplasty in hydronephrosis: examination of surgical results from a morphologic
      point of view.
AB  - BACKGROUND: Dilatation of the upper urinary tract is the most common congenital
      urogenital anomaly. Pyeloplasty is the therapy of choice in those patients with
      significant obstruction of the ureteropelvic junction. There are not many reports
      concerning the operative long-term results from a morphologic point of view.
      Furthermore, little information is available about children with giant
      hydronephrosis treated without resection of the dilated renal pelvis. METHODS:
      Between 1973 and 1993, 231 children with 262 renal units (kidney, renal pelvis,
      ureter) were treated at our institution. Giant hydronephrosis was observed in 52
      renal units. The clinical and follow-up data were obtained from the patients'
      records. The dilatation of the upper urinary tract, confirmed by means of
      intravenous pyelogram, was divided into 5 grades. RESULTS: In 215 renal units,
      reconstructive surgery was performed without reduction of the renal pelvis.
      Revision of the pyeloplasty was necessary in 5 of the 215 renal units. The
      dilatation of the upper urinary tract improved or remained stable in 99.4% of the
      renal units during the follow-up period of 4.8 years (range, 1 month to 21
      years). CONCLUSION: Surgical reconstruction of the ureteropelvic junction
      obstruction is a safe and successful procedure. The excision of the dilated
      pelvis does not seem to be necessary, even in patients with giant hydronephrosis.

PMID- 8886911
TI  - Risk factors in urinary calcium oxalate stone formation and their relation to
      urinary calcium oxalate supersaturation.
AB  - BACKGROUND: We studied the effect of potential risk factors of urinary calcium
      oxalate saturation on calcium oxalate stone formation. METHODS: Using the Equil2
      program, the DG values of calcium oxalate in 390 clinical urine specimens were
      estimated in 5 healthy male individuals with and without citrate therapy.
      RESULTS: Critical calcium-oxalate supersaturation (DG value, > 2.8) was noted in
      15 out of 390 urine specimens. Of the 15, 14 late night or morning specimens had
      critical calcium oxalate supersaturation, while only 1 afternoon specimen was
      supersaturated. Critical calcium oxalate supersaturation was often associated
      with hyperoxaluria and hypercalciuria, while undersaturation was often associated
      with hypomagnesiuria, a high Ca/Mg ratio, and hypocitraturia. CONCLUSIONS:
      Hypomagnesiuria, hypocitraturia, and a high Ca/Mg ratio appear to be poor
      indicators of calcium-oxalate supersaturation, and it is hard to predict the
      level of calcium-oxalate saturation using single parameters.

PMID- 8886912
TI  - Transition zone ratio and prostate-specific antigen density: the index of
      response of benign prostatic hypertrophy to an alpha blocker.
AB  - BACKGROUND: The aim of the present study was to determine whether the indices of
      transrectal ultrasonography (TRUS) are related to the clinical response to
      tamsulosin, a long-acting selective alpha 1-blocker. METHODS: Sixty patients with
      symptomatic benign prostatic hypertrophy (BPH) were treated with tamsulosin
      hydrochloride (0.2 mg/day) for 2 months. The findings on TRUS and uroflowmetry
      and the AUA symptom score before treatment were compared with those obtained at
      the end of the 2 month treatment period. For the indices of TRUS, transition zone
      (TZ) volume, transition zone ratio (TZ ratio = TZ volume/total prostate volume),
      total prostate volume, and prostate specific antigen density (PSAD) were
      calculated. RESULTS: There was a significant correlation between the pretreatment
      TZ ratio and the residual urine volume (r = 0.421, P = 0.0005). Patients with a
      lower TZ ratio and/or PSAD responded well to the treatment. The correlation
      between the PSAD value and the percent change in peak urinary flow rate was
      statistically significant (r = -0.432, P = 0.0009). CONCLUSION: TRUS provides
      simple parameters of PSAD that can be used to predict the response of patients to
      tamsulosin hydrochloride.

PMID- 8886913
TI  - PSA value adjusted for the transition zone volume in the diagnosis of prostate
      cancer.
AB  - BACKGROUND: The aim of the present study was to improve the accuracy of the
      prostate-specific antigen (PSA) density for detecting prostate cancer by using
      the transition zone (TZ) volume instead of the total prostate volume. METHODS:
      From April 1994 to October 1995, we examined 164 consecutive patients (52-88
      years old), with an elevated PSA and/or abnormal digital rectal examination. All
      patients underwent a transrectal ultrasound-guided biopsy. The PSA density for
      total prostate volume (PSAD) and for TZ volume (PSAT) were calculated from the
      transrectal ultrasound measurements. RESULTS: Forty-four of the 162 patients
      (27.2%) had histological confirmation of prostate cancer on biopsy. The area
      under the receiver-operator characteristic curve was 0.667 for PSA, 0.663 for
      PSAD, and 0.826 for PSAT. These areas were not significantly different for PSA
      and PSAD. However, PSAT was significantly superior to PSAD in differentiating
      benign hyperplasia from prostate cancer (P < 0.01). CONCLUSION: The TZ volume
      adjusted PSA density (PSAT) is useful for selecting patients for prostate biopsy
      from those with suspected prostate cancer.

PMID- 8886914
TI  - Radical prostatectomy for clinically localized prostate cancer: local tumor
      extension and prognosis.
AB  - BACKGROUND: This study was performed to evaluate the frequency of local tumor
      extension and its effect on disease progression after radical prostatectomy.
      METHODS: The study consisted of 66 consecutive men who underwent radical
      prostatectomy for clinically localized prostate cancer without any prior hormonal
      therapy. Cases were stratified according to pathologic findings. Sites of
      capsular penetration were also evaluated. RESULTS: The overall incidences of
      lymph node metastases, seminal vesicle invasion, capsular penetration, and
      positive surgical margin were, respectively, 23%, 32%, 55% and 35%. The disease
      progression rate in patients with positive lymph nodes differed significantly
      from that in those without nodal metastases (P < 0.0001). Although seminal
      vesicle invasion, capsular penetration, or positive surgical margin had an
      adverse effect on prognosis, the difference in progression missed statistical
      significance, when patients with positive lymph node metastases were excluded.
      The most common site of capsular penetration was posterolateral, in the area of
      the neurovascular bundle. CONCLUSIONS: Extraglandular tumor extension and
      positive surgical margins are common features of radical prostatectomy specimens.
      A nerve-sparing operation should be performed selectively and with great caution.
      The markedly adverse effect of lymph node involvement on progression must be
      accounted for when evaluating other variables relating to progression.

PMID- 8886915
TI  - Clinical applicability of a new tactile sensor for evaluating rigidity of the
      penis: a comparative study with Rigiscan.
AB  - BACKGROUND: A new tactile sensor was developed for detecting hardness of living
      tissue by Omata et al. in 1992. This paper reports applicability of the sensor
      for evaluation of penile rigidity. METHODS: Nine patients from a group of 12
      patients with penile erectile dysfunction were selected as subjects of this
      study. All patients agreed to artificial erection and monitoring of penile
      rigidity by a new tactile sensor and the Rigiscan system. The 9 patients selected
      all developed more than 1 cm circumferential expansion of the penis after an
      injection of smooth muscle relaxant into the corpus cavernosum. The sensor
      equipment consisted of a piezoelectric element that vibrated, and a pickup that
      detected vibration frequency. When the end of the sensor was pressed against a
      surface of the penis, the resonance frequency of the sensor changed and indicated
      rigidity of the organ. Rigidity of the penile shaft was simultaneously monitored
      with the sensor and the Rigiscan system before and after an injection of 40 mg
      papaverine or 20 micrograms prostaglandin E1. The sensor's measurements of
      rigidity were compared with those of Rigiscan. RESULTS: Reproducibility of
      rigidity measured with the tactile sensor was satisfactory. Statistical analysis
      was made on 85 simultaneous pairs of rigidity values from the tactile sensor and
      Rigiscan. The analysis indicated significant correlation between the values.
      CONCLUSION: The tactile sensor as well as Rigiscan will be of use for evaluating
      rigidity of the penis.

PMID- 8886916
TI  - Comparison of the Equil2 program and other methods for estimating the ion
      activity product of urinary calcium oxalate: a new simplified method is proposed.
AB  - BACKGROUND: We aimed to develop a new simplified method to determine the urinary
      calcium-oxalate saturation. METHODS: The ion-activity product (AP) of urinary
      calcium oxalate was estimated in 345 clinical urine specimens (all 2.5 hour
      collections) using the Equil2 computer program and several other methods, and the
      results were compared. A new index using 4 parameters was created using multiple
      regression analysis. RESULTS: Our new simplified method (the AP(CaOx) index EQ2)
      provided a better approximation to the Equil2 method (r = 0.9897) than other
      conventional methods. CONCLUSION: This new method requiring 4 factors (urinary
      calcium, magnesium, oxalate, and citrate concentrations) is simple and clinically
      usable.

PMID- 8886918
TI  - Gene expression of TGF-alpha, EGF and IL-6 in cultured renal tubular cells and
      renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is thought to arise from the renal tubular
      cells (RTC). Assuming that proliferating RTC imply a premalignant change of RTC
      into RCC, messenger RNA expressions of growth factors in cultured RTC were
      compared to both cultured and frozen noncultured RCC. METHODS: The expression of
      transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), EGF
      receptor (EGFR) and interleukin-6 (IL-6) were studied in surgically obtained RCC
      (n = 17), cultured RCC (n = 10), and autologous cultured RTC (n = 15).
      Quantitation of the PCR product was performed using a computer image analyzer
      which evaluated the intensity of each cytokine relative to beta-actin. RESULTS:
      TGF-alpha, EGFR and IL-6 were detected in most of the cultured RTC, and both
      cultured and noncultured RCC were also expressed at high levels. In contrast to a
      high positivity of TGF-alpha, EGF was not strongly positive in all specimens.
      CONCLUSIONS: Our results show that there is a predominant autocrine production of
      TGF-alpha in RCC and RTC, suggesting that TGF-alpha plays a distinct role in the
      proliferation of these cells. These studies also indicate that the mechanisms of
      proliferation and cytokine production of RCC and RTC are similar.

PMID- 8886917
TI  - Characterization of G proteins in obstructed kidneys.
AB  - BACKGROUND: Urinary tract obstruction has a marked effect on renal function.
      Activation of phospholipases which results in incremental production of
      vasoactive eicosanoids may contribute to the hemodynamic changes characteristic
      of an obstructed kidney. G proteins play an important role in transmembrane
      signal transduction, which control phospholipase activities and eicosanoid
      production. The present study was designed to determine the presence of G
      proteins in obstructed kidneys in rats, and to characterize the differences
      between unilateral ureteral obstruction (UUO) and bilateral ureteral obstruction
      (BUO). METHODS: Several G-protein alpha subunits (G alpha s, G alpha i1,2, and G
      alpha i3) and the beta subunit (G beta) were determined by immunoblotting and
      immunocytochemical techniques using specific antibodies against these G proteins.
      RESULTS: Immunoblots demonstrated a decreased G alpha i3 content in the outer
      medullary tubules and a significantly lower G beta level in the glomeruli of UUO.
      In BUO, there was an increased level of G beta in the cortical tubules, and the G
      alpha s level was markedly reduced in the inner medullary tubules.
      Immunocytochemical studies revealed that these G proteins were predominantly
      localized in the brush border side of the cortical tubules. However, we could not
      demonstrate staining differences between UUO and BUO. CONCLUSIONS: These results
      indicate that a modulation of G-protein-coupled transmembrane signal transduction
      may contribute to the renal functional changes in an obstructed kidney. A
      different level of expression of G-protein subunits between UUO and BUO may be a
      factor in the differences of hemodynamics and renal tubular damage between UUO
      and BUO.

PMID- 8886919
TI  - Laparoscopic nephropexy: a case report.
AB  - The laparoscopic approach is an ideal method for nephropexy because it produces
      less postoperative pain and allows an early recovery. We report a case of
      symptomatic renal ptosis treated laparoscopically with good success.

PMID- 8886920
TI  - Pyogenic vertebral osteomyelitis after acute bacterial prostatitis: a case
      report.
AB  - A case of pyogenic vertebral osteomyelitis after acute bacterial prostatitis in a
      78-year-old man is reported. The rarity and subtle clinical presentation of this
      condition, and the delayed appearance of radiologic signs of progression to
      destructive osteomyelitis, contributed to a significant delay in diagnosis. An
      arterial blood culture positive for bacterial growth during the episode of acute
      prostatitis suggested that bacteremia might result from hematogenous spread of
      the infection to the vertebral column via the venous system. Since intensive
      antimicrobial therapy proved ineffective, debridement of the first and second
      lumbar vertebral bodies, and anterior spinal fusion from the twelfth thoracic to
      the third lumbar vertebrae were performed. The patient's high fever and severe
      lumbago subsided immediately after the surgery. The possibility of development to
      pyogenic vertebral osteomyelitis should be kept in mind when treating a serious
      genitourinary tract infection.

PMID- 8886921
TI  - Locally-confined signet-ring cell carcinoma of the prostate: a case report of a
      long-term survivor.
AB  - It is generally believed that signet-ring cell carcinoma (SRCC) of the prostate
      is a high-grade neoplasm with a poor prognosis. We report a case of a long-term
      survivor diagnosed with localized prostatic SRCC (T3N0M0), who has been alive
      without any clinical evidence of disease for 100 months after combination therapy
      which consisted of local irradiation and hormone administration. A posttreatment
      needle biopsy confirmed the pathological complete response.

PMID- 8886922
TI  - Leiomyosarcoma of the vaginal wall causing difficulty in micturition: a case
      report.
AB  - A 52-year-old woman was admitted because of a vaginal-wall tumor adjacent to the
      external urethral orifice. The tumor had been causing disturbances in micturition
      for the past year. Magnetic resonance imaging and computed tomography images
      indicated a 6 x 3 cm solid mass in the anterior vaginal wall. The tumor was
      enucleated surgically through a median longitudinal incision of the anterior
      vaginal wall. Micturitional disturbances were rectified after surgery.
      Histologically, the tumor was a mixture of a high-cellularity area with a mitosis
      rate of 7 per 30 high-power fields, and a less cellular area without mitosis.
      Immunohistochemical staining was performed for both areas. The prognostic
      implications of the tumor are discussed.

PMID- 8886923
TI  - Anterior urethral diverticulum produced by Cowper's gland duct cyst.
AB  - A case of congenital urethral diverticulum is presented. The patient was a 16
      year-old boy with the chief complaint of dribbling urine since he was 14 years
      old. A retrograde urethrogram revealed a diverticulum of the bulbar urethra,
      which had been produced by a cystic dilation of the Cowper's gland duct. The
      walls of the diverticulum were resected endoscopically.

PMID- 8886924
TI  - Flow cytometric analysis of the H2O2-induced increase in intracellular Ca2+
      concentration of rat thymocytes.
AB  - The effect of hydrogen peroxide (H2O2) on the intracellular Ca2+ concentration
      ([Ca2+]i) of rat thymocytes was examined by a flow cytometer and two fluorescent
      dyes, fluo-3-AM and ethidium bromide, a dye impermeant to intact membranes, to
      characterize the H2O2-induced increase in [Ca2+]i. H2O2 at concentrations greater
      than 30 microM dose-dependently increased the [Ca2+]i of thymocytes which were
      not stained with ethidium. Removal of external Ca2+ greatly reduced the degree of
      H2O2-induced increase in [Ca2+]i. However, H2O2 still increased the [Ca2+]i under
      the external Ca(2+)-free condition. Diethylmaleate, which is known to produce a
      chemical depletion of cellular nonprotein thiol, significantly increased the
      [Ca2+]i. Dithiothreitol, which is used to protect cellular nonprotein thiol,
      slightly decreased the [Ca2+]i, but greatly reduced the H2O2-induced increase in
      [Ca2+]i. Therefore, it is considered that H2O2 may increase the [Ca2+]i through a
      mechanism related to the effects of H2O2 on the cellular nonprotein thiol.

PMID- 8886925
TI  - Inhibitory effect of glycyrrhetinic acid derivatives on capsaicin-induced ear
      edema in mice.
AB  - We examined the effect of glycyrrhetinic acid (Ia) and its derivatives on ear
      edema induced by topical application of capsaicin in mice. Three dihemiphthalate
      compounds: di-sodium salt of 18 beta-olean-12-ene-3 beta,30-diol
      (deoxoglycyrrhetol, IIa) di-O-hemiphthalate (IIb); 18 beta-olean-9(11),12-diene-3
      beta, 30-diol di-O-hemiphthalate (IIIa); and olean-11,13(18)-diene-3 beta,30-diol
      di-O-hemiphthalate (IVa) inhibited capsaicin-induced edema with ED50 values of
      52.6, 41.0 and 51.8 mg/kg (p.o.), respectively. However, glycyrrhetinic acid and
      deoxoglycyrrhetol at a dose of 200 mg/kg (p.o.) had no effect. Compound IIIa (100
      mg/kg, p.o.) also inhibited the edema response to capsaicin in mast cell
      deficient mice. Furthermore, compounds IIb, IIIa and IVa (25-100 mg/kg, p.o.)
      prevented ear edema in response to intradermal injection of substance P (SP) and
      compound 48/80. In addition, these compounds at a high dose of 100 mg/kg (p.o.)
      produced a significant inhibition of the plasma extravasation in ear skin induced
      by i.v. administration of SP. The above results suggest that the effect of these
      compounds on capsaicin-induced ear edema is due at least in part to an inhibition
      of the increase of vascular permeability induced by vasoactive agents released
      from mast cells. Moreover, it seems likely that these compounds at a high dose
      can suppress vasodilatation and plasma extravasation induced by SP involved in
      capsaicin-induced edema.

PMID- 8886926
TI  - Effect of fluvoxamine on 5-hydroxytryptamine uptake, paroxetine binding sites and
      ketanserin binding sites in the Japanese monkey brain and platelets, in vivo and
      in vitro.
AB  - We investigated the in vitro effects of fluvoxamine on 3H-paroxetine binding and
      3H-monoamine uptake in monkey cerebral cortex in comparison with those of other
      antidepressants. Fluvoxamine selectively inhibited 3H-5-hydroxytryptamine (5-HT)
      uptake and 3H-paroxetine binding. However, it did not alter 3H-norepinephrine or
      3H-dopamine uptake. In addition, we examined the effects of chronic treatment
      with fluvoxamine (5 mg/kg per day, p.o.) on 5-HT uptake sites that bind 3H
      paroxetine and 5-HT2 receptors that bind 3H-ketanserin, in monkey brains and
      platelets. Chronic treatment with fluvoxamine affected neither the paroxetine
      binding sites nor the kentanserin binding sites of the brains and platelets.
      These results suggest that long-term treatment with fluvoxamine does not affect
      either the 5-HT uptake sites or 5-HT2-receptors of 5-HT neurons in monkey brain
      in spite of its strong inhibitory effect on 5-HT uptake in vitro.

PMID- 8886927
TI  - Fluorescent estimation of H2O2-induced changes in cell viability and cellular
      nonprotein thiol level of dissociated rat thymocytes.
AB  - We have developed a procedure to simultaneously estimate cell viability and the
      cellular level of nonprotein thiol (presumably glutathione) using two fluorescent
      dyes, 5-chloromethylfluorescein (5CMF) and ethidium, and rat thymocytes.
      Diethylmaleate and N-ethylmaleimide reduced, respectively, the intensity of 5CMF
      fluorescence to 0.23 and 0.1, relative to the control. Incubation with buthionine
      sulfoximine, an inhibitor of glutathione synthesis, decreased the intensity of
      5CMF fluorescence to 0.61. Results indicate that 5CMF fluorescence can be
      attenuated by agents that decrease the level of cellular nonprotein thiols,
      suggesting that 5CMF fluorescence is utilized for estimating the level of
      cellular glutathione. Hydrogen peroxide (10 microM to 3 mM) reduced the intensity
      of 5CMF fluorescence in a dose-dependent manner and increased the number of
      thymocytes stained with ethidium (presumably dead cells or cells with compromised
      membranes) at concentrations of 300 microM or greater. Reduction of cellular
      glutathione level seems to precede cell death in which oxidative stress is
      involved.

PMID- 8886928
TI  - Antagonistic effect of YM022, an antiulcer agent in rats, on human
      cholecystokinin (CCK)B/gastrin receptor.
AB  - We recently isolated a cDNA clone for the human cholecystokinin (CCK)B/gastrin
      receptor and permanently expressed this receptor cDNA in NIH-3T3 cells. [125I]CCK
      8 specifically bound to the membrane of the transfectant, and this binding was
      displaced by unlabeled CCK-8 with an IC50 of 0.32 nM. Treatment of these cells
      with CCK-8 increased the intracellular Ca2+ concentration with an EC50 of 0.30
      nM. Using these cells expressing functional human CCKB/gastrin receptors, we
      investigated the pharmacological properties of (R)-1-[2,3-dihydro-1-(2'
      methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl)
      urea (YM022), a potent and selective CCKB/gastrin receptor antagonist in rats.
      YM022 potently inhibited [125I]CCK-8 binding to the membrane with an IC50 of 55
      pM and CCK-8-induced Ca2+ mobilization with that of 7.4 nM. On the other hand,
      its racemate and enantiomer more weakly inhibited this binding (IC50 of 110 pM
      and 11 nM, respectively) and Ca2+ mobilization (IC50 of 18 nM and 94 nM,
      respectively). These results indicate that YM022 stereoselectively recognizes the
      human CCKB/gastrin receptor as a potent antagonist and that the established
      transfectant is useful for characterization of human CCKB/gastrin-receptor
      ligands.

PMID- 8886929
TI  - A rapid- and short-acting hypoglycemic agent KAD-1229 improves post-prandial
      hyperglycemia and diabetic complications in streptozotocin-induced non-insulin
      dependent diabetes mellitus rats.
AB  - We investigated therapeutic effects of a rapid- and short-acting non-sulfonylurea
      hypoglycemic agent, calcium (2S)-2-benzyl-3-(cis-hexahydro-2
      isoindolinylcarbonyl)propionate dihydrate (KAD-1229), on streptozotocin (STZ)
      induced non-insulin-dependent diabetes mellitus (NIDDM) rats. The effects exerted
      by KAD-1229 on the post-prandial plasma glucose rise in STZ-induced mild NIDDM
      (mNIDDM) rats were different from those of sulfonylureas. When KAD-1229 with
      liquid meal (10 kcal/kg) was given to the mNIDDM rats, the plasma glucose
      migration was similar to that of normal healthy rats. On the contrary,
      glibenclamide had little or no effect on the plasma glucose rise 0.5-1 hr after
      oral administration, and its effect was only evident 2-5 hr after dosing.
      Tolbutamide showed similar hypoglycemia to that induced by glibenclamide at 2-5
      hr with insufficient efficacy at 0.5 hr. Gliclazide sufficiently suppressed the
      level of post-prandial plasma glucose. However, its complete inhibition of post
      prandial plasma glucose was associated with the extra-hypoglycemia 1-5 hr after
      oral administration. We also tested the efficacy of KAD-1229 in more severe STZ
      induced NIDDM (sNIDDM) rats to elucidate the effects of the drug on the long-term
      glycemic controls and diabetic complications. When the sNIDDM rats were treated
      with 10 mg/kg KAD-1229 twice a day for about 17 weeks, increases in fasting
      plasma glucose and hemoglobin A1c were inhibited. Furthermore, treatment with KAD
      1229 suppressed the development of microalbuminuria and cortical cataract. We
      conclude that the rapid- and short-acting insulinotropic agent KAD-1229 is able
      to improve the deterioration in the glycemic controls and inhibit the development
      of diabetic complications in STZ-induced NIDDM rats.

PMID- 8886930
TI  - Alpha 1B-adrenoceptor subtype mediating the phenylephrine-induced contractile
      response in rabbit corpus cavernosum penis.
AB  - The alpha 1-adrenoceptor subtype mediating contraction to phenylephrine in rabbit
      corpus cavernosum penis (CCP) was investigated using selective alpha 1
      adrenoceptor subtype antagonists. WB4101 ((2-(2,6-dimethoxy-phenoxyethyl)
      aminomethyl-1, 4-benzodioxane) hydrochloride), 5-methylurapidil and tamsulosin
      concentration-dependently produced a parallel rightward shift of the
      concentration-response curve to phenylephrine, yielding pKB values of 8.05, 7.59
      and 9.21, respectively. The slopes of the Schild plots were not different from
      unity. These antagonists did not affect the maximum response to phenylephrine.
      Oxymetazoline (1 microM), which initially caused a small contraction, produced a
      parallel rightward shift of the concentration-response curve to phenylephrine
      with an apparent pKB value of 6.99. However, oxymetazoline seemed to act as a non
      surmountable antagonist to the phenylephrine-induced contraction, reducing the
      maximum response by 71.1%. Chloroethylclonidine (25 and 100 microM) produced a
      parallel rightward shift of the concentration-response curve to phenylephrine
      without altering the maximum response. These results show that the alpha 1
      adrenoceptor in rabbit CCP has a relatively low affinity for WB4101, 5
      methylurapidil, tamsulosin and oxymetazoline and is sensitive to inactivation by
      chloroethylclonidine. It is suggested that the alpha 1-adrenoceptor subtype
      mediating contraction to phenylephrine in rabbit CCP has the characteristics of
      the alpha 1B-adrenoceptor subtype.

PMID- 8886931
TI  - Negative chronotropic and inotropic effects of U-92032, a novel T-type Ca2+
      channel blocker, on the isolated, blood-perfused dog atrium.
AB  - We investigated the effects of U-92032 ((7-((bis-4-fluorophenyl) methyl)-1
      piperazinyl)-2-2(2-hydroxyethylamino)-4-(1-methylethyl)- 2,4, 6-cycloheptatrien-1
      one), a novel T-type Ca2+ channel blocker, on sinus rate and atrial contractile
      force in the isolated, blood-perfused atrium of the dog. U-92032 (1 to 300 nmol)
      induced negative chronotropic and inotropic responses in a dose-dependent manner,
      and the percentage decrease in sinus rate was less than that in atrial
      contractile force. Atropine did not affect the negative responses to U-92032.
      These results suggest that U-92032, a T-type Ca2+ channel blocker, simultaneously
      decreases the sinus rate and atrial force as do L-type Ca2+ channel blockers in
      the isolated dog atrium.

PMID- 8886932
TI  - The mode of inhibitory action of alpha-mangostin, a novel inhibitor, on the
      sarcoplasmic reticulum Ca(2+)-pumping ATPase from rabbit skeletal muscle.
AB  - alpha-Mangostin, the principal ingredient of the fruit hull of Garcinia
      mangostana, caused a concentration-dependent decrease in the activities of both
      Ca(2+)-ATPase and Ca(2+)-transport of the sarcoplasmic reticulum from rabbit
      skeletal muscle with an IC50 value of 5 microM. Neither Ca2+ release nor other
      enzyme activities were affected by alpha-mangostin. Kinetic analysis of the
      inhibitory effects of alpha-mangostin on Ca(2+)-ATPase suggests that the
      inhibition of the ATPase is a noncompetitive-type with respect to ATP or Ca2+.
      alpha-Mangostin may become a useful pharmacological tool for clarifying the
      physiological functions of Ca(2+)-pumping ATPase and sarcoplasmic reticulum.

PMID- 8886933
TI  - Expression of low-molecular-weight kininogen mRNA in human fibroblast WI38 cells.
AB  - Expression of the low-molecular-weight kininogen (L-kininogen) mRNA in the human
      fibroblast cell line WI38 was examined by means of the reverse-transcription
      polymerase chain reaction and Southern blotting using human L-kininogen cDNA as a
      probe. The results demonstrated that WI38 fibroblasts expressed L-kininogen mRNA
      and that the expression was stimulated by 1 mM dibutyryl cAMP or 10 microM
      prostaglandin E2. Dexamethasone (1 microM) inhibited the stimulatory effect of
      prostaglandin E2. These results suggest that human fibroblasts supply L
      kininogen, a protein precursor of the inflammatory mediator kinins, to connective
      tissues in response to inflammatory stimuli and that glucocorticoids may exert
      the antiinflammatory effect in part by inhibiting the local production of L
      kininogen.

PMID- 8886934
TI  - The possible involvement of GABAA systems in the antinarcotic effect of
      majonoside-R2, a major constituent of Vietnamese ginseng, in mice.
AB  - The effect of majonoside-R2 on morphine- and U-50,488H-induced antinociception
      was examined by the tail-pinch test in mice and compared with that of diazepam.
      Majonoside-R2 and diazepam inhibited the morphine- and U-50,488H-induced
      antinociception, and the actions were antagonized by the benzodiazepine receptor
      antagonist flumazenil and the GABA-gated CI- channel blocker picrotoxin. Diazepam
      but not majonoside-R2 exhibited a protective activity against convulsion caused
      by the GABAA antagonists bicuculline and picrotoxin. These results indicate that
      GABAA systems are involved in the effect of majonoside-R2 on the opioid-induced
      antinociception and suggest that the mechanisms of action of majonoside-R2 may
      differ from those of diazepam.

PMID- 8886935
TI  - Neuroprotective effect of TTC-909, an isocarbacyclin methyl ester incorporated in
      lipid microspheres, on hippocampal delayed neuronal death of stroke-prone
      spontaneously hypertensive rats.
AB  - TTC-909 is a newly developed isocarbacyclin methyl ester (TEI-9090) incorporated
      in lipid microspheres. The neuroprotective effect of TTC-909 was histologically
      examined in the pyramidal cell layer of the hippocampus CA1 subfield 7 days after
      transient forebrain ischemia using stroke-prone spontaneously hypertensive rats.
      TTC-909, given intravenously 10 min after the transient forebrain ischemia, dose
      dependently protected against ischemia-related delayed neuronal death. The blood
      pressure remained unchanged following TTC-909 administration. This finding
      suggests that TTC-909 has a neuroprotective action on ischemic delayed neuronal
      death in the hippocampus.

PMID- 8886936
TI  - A potent mu-opioid receptor agonist, dihydroetorphine, fails to produce the
      conditioned place preference in mice.
AB  - Reinforcing effects of dihydroetorphine (DHE) and morphine were evaluated by the
      conditioned place preference paradigm. Both DHE and morphine produced an
      antinociceptive effect in a dose-dependent manner. On the other hand, DHE (0.1,
      1, 3 and 10 micrograms/kg, i.p.) failed to induce the conditioned preference,
      while morphine (0.1, 1, 3 and 10 mg/kg, i.p.) caused a dose-dependent preference
      for the drug-paired place. Thus, these characteristic properties of DHE make it
      attractive for development as a novel potent analgesic compound that has less
      dependence liability.

PMID- 8886937
TI  - Effects of sematilide, a novel class III antiarrhythmic agent, on delayed
      rectifier K+ current in guinea pig atrial myocytes.
AB  - Effects of sematilide, a novel class III antiarrhythmic agent, on the delayed
      rectifier K+ current (Ik) were examined in guinea pig atrial myocytes using a
      voltage clamp technique. Sematilide inhibited both time-dependent outward current
      upon depolarization and tail currents (Ik-tail) at -40 mV. The concentration of
      sematilide required for a 50% decrease in Ik-tail was approximately 50 microM.
      The sematilide-sensitive current obtained using a triangular voltage command
      exhibited marked inward rectification and had the maximum amplitude at -30 mV.
      These results suggest that sematilide inhibits rapidly activating Ik in guinea
      pig atrial myocytes, resulting in the prolongation of action potential duration
      and refractoriness.

PMID- 8886938
TI  - Children's responding to live interadult conflict: the role of form of anger
      expression.
AB  - Children's responses to interadult arguments were examined as a function of three
      forms of disputes: covert, verbal, and physical. Four- to seven-year-olds' overt
      behavioral responses to live enactments of arguments between a male and a female
      were videotaped and coded for behavioral distress and anger/aggression, and
      children were then interviewed. Although children exhibited overt-behavioral
      distress in response to all forms of disputes, physical arguments evoked the
      highest levels of distress. Some gender differences in responding were observed.
      In comparison to boys, girls exhibited more overt distress during the arguments,
      and wanted to stop physical arguments more frequently. The results extend
      findings based on the videotape methodology of the presentation of interadult
      arguments indicating that form of anger expression impacts children's emotional
      responding to interadult conflict.

PMID- 8886939
TI  - Establishing the constructs of childhood behavioral disturbances in a Chinese
      population: a questionnaire study.
AB  - The behavioral problems of Chinese children were examined in a questionnaire
      study of a representative sample of 3,069 seven-year-old Chinese schoolboys in
      Hong Kong using Rutter's questionnaires for completion by parents and teachers.
      Separate robust dimensions of hyperactivity, antisocial, and neurotic behaviors
      were evident. The correlations among different dimensions were similar to those
      reported in the West. Short-term longitudinal analysis suggested that these
      dimensions were stable over time and that antisocial behaviors might develop in
      hyperactive children. The finding highlights the necessity of differentiating the
      hyperactive domain from the antisocial one. A significant source effect was found
      in all three dimensions. Chinese schoolboys had nearly two times the level of
      questionnaire-rated hyperactivity compared with school boys in the West; but it
      is premature to conclude that hyperactivity is more common in Chinese schoolboys
      in Hong Kong. Cross-cultural differences in adults' expectations and tolerance
      remain a plausible explanation.

PMID- 8886940
TI  - The Brief Reasons for Living Inventory for Adolescents (BRFL-A).
AB  - This study modified and evaluated the psychometric properties of the Reasons for
      Living Inventory (RFL) in samples of adolescents. Internal consistency
      reliability, corrected item-total scale correlation, and exploratory factor
      analysis procedures were used with a mixed sample of 260 adolescents to identify
      14 items for the brief version of the RFL (BRFL-A). Confirmatory factor analyses
      provided support for the five-factor oblique structure of the BRFL-A in a
      psychiatric inpatient sample with a range of suicidal behaviors. Reliabilities of
      the BRFL-A subscales were satisfactory. Four of the five subscales differentiated
      between suicidal and nonsuicidal adolescents. Significant correlations were found
      between three BRFL-A subscales and several suicide indices. Convergent
      discriminant validity was examined by correlating the BRFL-A subscales with the
      Minnesota Multiphasic Personality Inventory-Adolescents (MMPI-A) Content Scales.
      Limitations of the study are discussed.

PMID- 8886941
TI  - The course of aggression in first-grade children with and without comorbid
      anxious symptoms.
AB  - We studied the course of aggressive behavior in an epidemiologically defined
      sample of first graders with and without comorbid anxious symptoms. Our primary
      purpose in doing so was to understand whether the stability of aggression in
      young children was attenuated or strengthened in the presence of comorbid
      anxiety. Previous studies of older children and adolescents had produced
      equivocal findings in this regard. Data on anxious symptoms were obtained through
      an interview of the children, whereas aggressive behavior was assessed through
      the use of a teacher interview and peer nominations. Assessments were performed
      in the fall and spring of first grade. In contrast to children classified as
      aggressive alone in the fall of first grade, boys and girls classified as
      aggressive and anxious in the fall of first grade were significantly more likely
      to be classified as aggressive in the spring in terms of teacher ratings and/or
      peer nominations of aggression. Thus our findings suggest that the link between
      early and later aggression may be strengthened in the presence of comorbid
      anxious symptoms, rather than attenuated. Future studies are needed to identify
      the mechanisms by which the course of aggression is influenced by the presence of
      comorbid anxiety.

PMID- 8886942
TI  - Attributional styles of aggressive boys and their mothers.
AB  - To determine if mothers of aggressive boys have the same propensity as their sons
      to infer hostile intentions in ambiguous interpersonal situations, 50 mothers of
      aggressive and nonaggressive boys were each asked to interpret hypothetical
      situations involving themselves with their child, their partner, and a peer as
      well as hypothetical situations involving their child in interaction with
      classmates and teachers. Their sons also were each requested to interpret
      hypothetical situations involving themselves with their mother, a teacher, and a
      classmate. The results indicated that mothers of aggressive boys do share the
      propensity to infer hostility in ambiguous situations and may, in effect, model a
      hostile attributional bias. Mothers of aggressive boys failed to differentiate
      ambiguous from hostile situations and were as likely to infer hostile intentions
      in ambiguous as in hostile situations. The results also suggest a generalized
      tendency on the part of mothers of aggressive boys to infer negative motives
      and/or dispositions when accounting for the noxious behavior of their sons.
      Further, for the aggressive boys, the hostile attributional bias was evident with
      both peers and teachers. The presence of a hostile attribution was predictive of
      an aggressive response for the aggressive boys. Even in the face of clearly
      hostile, provocative behavior, nonaggressive boys were less likely to offer
      aggressive solutions than aggressive boys.

PMID- 8886943
TI  - A revised teacher rating scale for reactive and proactive aggression.
AB  - A teacher rating scale of reactive aggression, proactive aggression, and covert
      antisocial behavior was evaluated in a normative sample of third- to fifth-grade
      predominantly white lower middle class boys (N = 186). Factor analysis revealed
      independent and internally consistent Reactive Aggression (six reactive items),
      and Proactive Aggression (five proactive items, five covert items) factors.
      Although the factors were intercorrelated (r = .67), and each factor was
      significantly correlated with negative peer social status (r = .26 for each,
      controlling for grade), the independence of the factors was supported by the
      unique relation of Reactive Aggression with in-school detentions (r = .31),
      controlling for Proactive Aggression and grade. These results supported the
      reliability and validity of Reactive and Proactive Aggression as rated by
      teachers, which should facilitate further research of these constructs.

PMID- 8886944
TI  - Neuropsychological functioning, motor speed, and language processing in boys with
      and without ADHD.
AB  - We administered a neuropsychological battery to boys aged 6 to 12 years old
      diagnosed with attention-deficit hyperactivity disorder (ADHD; n = 51) and to
      comparison boys of the same age range (n = 31). Boys with ADHD had greater
      difficulty than comparison youngsters on nonautomated language and motor tasks
      administered with a fast instructional set and on one of two traditional frontal
      executive measures (Porteus mazes). When tasks requiring automatic processing
      were paired with similar tasks requiring greater use of selective attention
      processes, the latter, controlled processing tasks differentiated groups better
      than did automated tasks. This differential effect of otherwise similar tasks is
      interpreted in terms of an output deficit mediated by response organization as
      detailed in the information processing literature. The ADHD group also exhibited
      slow gross motor output, measured independently of verbal output. The findings
      are evaluated in terms of both Luria's (1973) tripartite model of neurocognitive
      organization and frontal striatal models, with an emphasis on output processes.
      The observed language deficits could represent frontal lobe processes intricately
      related to self-monitoring and planning. The utility of controlled processing,
      self-paced tasks with fast instructional sets in assessing language and motor
      skills in ADHD is highlighted.

PMID- 8886945
TI  - The short-term consequences of early onset cannabis use.
AB  - The associations between early onset (prior to 15 years of age) cannabis use and
      rates of mental health or adjustment problems during the period from 15 to 16
      years of age were studied in a New Zealand birth cohort. Early onset cannabis
      users were at increased risks of later substance use behaviors,
      conduct/oppositional disorders, juvenile offending, severe truancy, school
      dropout, anxiety, depression, and suicidal ideation. Early cannabis users had
      odds of these outcomes ranging from 2.7 to 30.8 times higher than the odds for
      those who did not use cannabis prior to age 15. Most of the elevated risks of
      early onset users were explained by the fact that they were a high-risk groups of
      adolescents characterized by family disadvantages, early adjustment problems, and
      high affiliations with substance-using or delinquent peers. Nonetheless, even
      after adjustment for a wide range of confounding factors, early onset users had
      increased risks of later cannabis use. It is concluded that while most of the
      elevated risks of early onset users were explained by social, family, and
      individual characteristics of this group, early onset users were at increased
      risks of later cannabis use.

PMID- 8886946
TI  - Preschool children with externalizing behaviors: experience of fathers and
      mothers.
AB  - Childhood behavior disorders are related to family stress and maladjustment.
      Little is known, however, about the adjustment of families with preschool-aged
      children at risk for subsequent behavior disorders. Moreover, fathers'
      perceptions of child problem behavior and their reactions to it generally have
      been neglected. Subjects were mothers and fathers of 52 preschool-aged children
      assigned to one of three groups: control, moderate externalizing, and high
      externalizing. Higher child externalizing behavior was associated with greater
      negative family impact, lowered parenting sense of efficacy, and child-rearing
      practices that were more authoritarian and less authoritative. Mothers and
      fathers did not differ in actual perceived level of child behavior problems,
      although both believed that mothers saw more problems. Child Group x Parent
      interactions indicated that mothers experienced increased stress and a need for
      help with moderate as well as high child externalizing behaviors, whereas fathers
      were not elevated on these measures unless the child's externalizing behaviors
      were high. Implications of these findings for early family intervention are
      considered.

PMID- 8886947
TI  - Histomorphometric study of age-related changes in remodelling activity of human
      desmodontal bone.
AB  - To study age-related changes in human desmodontal bone remodelling, histological
      specimens were prepared from 42 human mandibles from individuals aged between 16
      and 71 years which were obtained from autopsies. Microradiographs of horizontal
      ground sections and the corresponding undecalcified histological sections stained
      with Goldner trichrome were used for analysis. Histomorphometric measurements of
      static bone remodelling were performed along the desmodontal bone surface using a
      computer assisted semiautomatic measurement system. External influences from the
      individual dental occlusion and periodontal conditions were superimposed on age
      changes. A modest but significant age-dependent decrease in the surface extent of
      osteoid seams covered by 'active' osteoblasts was found. In addition, the number
      of osteoclasts per unit of resorptive bone surface diminished, leading to an
      increase in Howship's lacunae, devoid of osteoclasts. Both phenomena were
      interpreted as being due to a decrease in active bone forming capacity with age.

PMID- 8886948
TI  - Early intestinal microparticle uptake in the rat.
AB  - This time-course study investigates the early uptake and passage of
      microparticles across the intestinal mucosa. Single intraoral doses of
      fluorescent latex particles, 1.82 microns in diameter, were administered to young
      adult male, nonfasted rats at a dose of 1.88 x 10(9) particles. Peyer's patch
      regions and mesenteric lymph nodes were collected at 5, 15 and 30 min time points
      for both bulk tissue and morphological analyses. Particles were found at all
      experimental time points in macerated intestinal and nodal specimens: particle
      numbers were higher in proximal than in distal intestine at all time points
      despite the fact that particle numbers in distal Peyer's patch regions increased
      with time. Particle numbers in mesenteric lymph nodes also increased with time
      after administration. Detailed morphological data for several intestinal and
      nodal tissue compartments showed substantial early uptake of particles by villous
      epithelium, including goblet cells, but low involvement of follicle-associated
      cells. The distribution of particles in the lymph nodes confirmed that
      translocation occurred to all nodal compartments. These studies give confirmatory
      evidence that uptake and translocation of microparticles may take place as early
      as 5 min after administration and suggest that intestinal region may influence
      uptake.

PMID- 8886949
TI  - Catecholaminergic and serotoninergic fibres innervate the ventricular system of
      the hedgehog CNS.
AB  - Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and
      noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the
      ventricular system of the hedgehog Erinaceus europaeus. Light microscopic
      examination of immunocytochemically stained sections revealed that the
      ventricular system of the hedgehog is unique among mammals in that the choroid
      plexuses receive CA axons and that the supraependyma and subependyma of the
      cerebral ventricles and the spinal central canal are innervated both by
      serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were
      generally more abundant and created at places a large number of interconnected
      basket-like structures, whereas CA fibres were usually directed towards the
      ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the
      ependyma lining grey matter, whereas a higher 5-HT innervation density was
      observed in the area between the corpus callosum and the caudate nucleus or the
      septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher
      5-HT and NA innervation density, whereas DA fibres were preferentially
      distributed in the ventral half of the basal region. The ependyma lining the
      cerebral aqueduct displayed a higher MA innervation density in its ventral part.
      The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT
      innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and
      only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the
      ependyma of the central canal. Finally, the circumventricular organs were
      unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic
      innervation of the hedgehog ventricular system described here probably reflects a
      transitory evolutionary stage in the phylogeny of the MA systems with presently
      unknown functional implications.

PMID- 8886950
TI  - Innervation of the palpebral conjunctiva and the superior tarsal muscle in the
      cynomolgous monkey: a retrograde fluorescent tracing study.
AB  - Retrograde fluorescent transport of Fast Blue (FB) and Diamidino Yellow (DY) was
      used to study the localisation of neurons that innervate the palpebral
      conjunctiva and the superior tarsal muscle in the cynomolgous monkey. Labelled
      cell bodies of sensory neurons including a few double labelled cell bodies were
      found in the ophthalmic part of the ipsilateral trigeminal ganglion. Labelled
      cell bodies of the sympathetic neurons including a few double labelled cell
      bodies were located in the middle and cranial part of the ipsilateral superior
      cervical ganglion, with a few in the contralateral ganglion. Labelled cell bodies
      of the parasympathetic neurons were all found in the ipsilateral pterygopalatine
      ganglion and randomly distributed. Neurons were disposed in the opthalmic part of
      the trigeminal and superior cervical ganglia, whereas parasympathetic neurons
      were distributed randomly. Cells of the nodose, ciliary, geniculate, otic and
      first 3 spinal ganglia were unlabelled. Tracing FB and DY from the palpebral
      conjunctiva and superior tarsal muscle respectively, revealed double labelled
      neurons in the trigeminal and superior cervical ganglia, probably indicating the
      presence of collaterals of axons serving both the palpebral conjunctiva and the
      superior tarsal muscle.

PMID- 8886951
TI  - The influence of predegenerated nerve grafts on axonal regeneration from
      prelesioned peripheral nerves.
AB  - Recent in vitro work has indicated that predegenerated segments of peripheral
      nerve are more capable of supporting neurite growth from adult neurons than fresh
      segments of nerve, whereas previous in vivo studies which investigated whether
      predegenerated nerve segments used as grafts are capable of enhancing axonal
      regeneration produced conflicting results. We have reinvestigated this question
      by using predegenerated nerve grafts in combination with conditioning lesions of
      the host nerve to determine the optimal conditions for obtaining the maximal
      degree of regeneration of myelinated axons. The sciatic nerve of adult Dark
      Agouti rats were sectioned at midthigh level, and the distal portion was allowed
      to predegenerate for 0, 6 or 12 d in situ. 10-15 mm lengths of these distal nerve
      segments were then syngenically grafted onto the central stumps of sciatic nerves
      which had themselves received a conditioning lesion 0, 6, and 12 d previously,
      making a total of 9 different donor-host combinations. The grafts were assessed
      histologically 3 or 8 wk after grafting. Axonal regeneration in the 9 different
      donor-host combinations was determined by counting the numbers of myelinated
      axons in transverse sections through the grafts. All grafts examined contained
      regenerating myelinated axons. The rats given a 3 wk postgrafting survival period
      had an average of between 1400 and 5300 such axons. The rats given an 8 wk
      postgrafting survival period had between about 13,000 and 25,000 regenerating
      myelinated axons. Analysis of variance revealed significant main effects for both
      the Donor and Host conditions as well as Weeks (i.e. survival period after
      grafting). These results indicate that both a conditioning lesion of the host
      neurons and the degree of predegeneration of peripheral nerve segments to be used
      as grafts are of importance in influencing the degree of axonal regeneration. Of
      these 2 factors the conditioning lesion of the host appears to have the greater
      effect on the final number of regenerating myelinated axons.

PMID- 8886952
TI  - Human gastric intrinsic factor expression is not restricted to parietal cells.
AB  - Gastric parietal cells have been accepted as the only site of intrinsic factor
      production in the human stomach. In animals, however, intrinsic factor has been
      localised to various other cell types of foregut origin, including chief and
      enteroendocrine cells in gastric mucosa, and duct cells from salivary glands and
      pancreas. The availability of recombinant human intrinsic factor has led to
      production of high titre, monospecific antiserum which was used to reexamine the
      distribution and subcellular localisation of intrinsic factor in the human
      stomach. Immunolight microscopy revealed that most positively stained cells were
      gastric parietal cells, but at the margins of the anatomical regions (e.g.
      cardia/fundus, body/antrum) clusters of gastric chief cells and individual
      enteroendocrine cells were found to contain intrinsic factor. Immunoelectron
      microscopy demonstrated the highest antigen density on endocytic and apical
      membranes of parietal cells. Exocrine secretory granules of a subpopulation of
      chief cells, the secretory granules of some enteroendocrine cells, and the plasma
      membranes and smooth vesicles of endothelial cells of the lamina propria
      capillaries underlying enteroendocrine cells were also positive for the antigen.
      Labelling in all cells was specific, as it was abolished by preabsorption of the
      antisera with purified recombinant human intrinsic factor. These findings
      demonstrate a potential for cellular expression of human intrinsic factor in
      nonparietal cells. Because such expression occurs normally at the margins of
      anatomical gastric regions, it suggests that local factors may influence
      expression of intrinsic factor.

PMID- 8886953
TI  - Unilateral innervation of guinea pig vallate taste buds as determined by
      glossopharyngeal neurectomy and HRP neural tracing.
AB  - The innervation pattern by primary afferent nerve fibres and the neurotrophic
      effect on taste cells were investigated in the guinea pig vallate taste bud by
      means of glossopharyngeal neurectomy and horseradish peroxidase (HRP) or wheat
      germ agglutinin-horseradish peroxidase (WGA-HRP) tracing. In the glossopharyngeal
      neurectomy study, taste buds in the vallate papillae of adult guinea pigs were
      denervated by unilateral resection of the right glossopharyngeal nerve.
      Denervated animals were killed on days 1, 3 and 5 and weeks 1-9, 12 and 24
      postneurectomy. The results showed that, on the denervated side, the taste buds
      decreased significantly in number during the 1st 2 wk, and disappeared completely
      by wk 3; no mature taste buds were present even 24 wk after neurectomy. This
      suggests that the vallate taste buds disappear in the absence of the
      glossopharyngeal nerve. In the neural tracing study, HRP or WGA-HRP was injected
      into the proximal end of the right glossopharyngeal nerve, near the jugular
      foramen. After a survival time of 24 h, the vallate papillae were sectioned and
      examined by light and electron microscopy. Light microscopy revealed that the HRP
      or WGA-HRP-labelled fibres innervated the vallate taste buds of the injected
      side. Most of the taste cells in the buds were labelled with HRP or WGA-HRP
      reaction products from the basal to the apical region. At the ultrastructural
      level, the reaction products were confined to the cytoplasm of the labelled
      cells, which were identified as type I, II and III cells, but not basal cells.
      Labelled intragemmal nerve profiles were seen among the taste cells. No synapse
      formation was seen with nerve profiles abutting on type I and II cells, whereas
      on certain type III cells, typical synapses were formed. We conclude that both
      the right and left vallate papilla in the guinea pig are unilaterally innervated
      by the glossopharyngeal nerve without cross-innervation.

PMID- 8886954
TI  - Morphological characteristics of mouse incisor enamel.
AB  - Maxillary and mandibular incisors of mice aged 5 wk were sectioned and ground
      along various planes, acidetched and observed by scanning electron microscopy
      (SEM). The general design of the enamel structure resembled rat incisor enamel
      with an uniserial lamellar pattern of prisms in the inner enamel and incisally
      directed parallel prisms in the outer enamel. The centrolabial thickness of the
      enamel was about 60 microns in the maxillary and about 95 microns in the
      mandibular incisor. The angle between prism rows and enamel-dentine junction was
      about 70 degrees in the maxillary and about 45 degrees in the mandibular incisor,
      while the angle of decussation, which increased from the enamel-dentine junction
      towards the outer enamel, was 50-95 degrees and 30-80 degrees respectively. The
      angle between outer enamel prisms and enamel surface was about 12 degrees in the
      maxillary and 5-15 degrees in the mandibular incisor. The outer 1/2-1/3 of the
      outer enamel contained iron and was more acid-resistant than the rest of the
      enamel. The superficial 3-5 microns was prismless with a Fe/Ca ratio of about
      25/75 in the maxillary and about 10/90 in the mandibular incisor. The latter
      concentration of iron was insufficient to give visible pigmentation to the
      enamel. The extreme mesial and lateral enamel was neither typical of inner nor of
      outer enamel. Assuming that the length of the zone of enamel secretion is half
      the corresponding length in the rat, it could be calculated that ameloblasts in
      mouse mandibular incisors produce enamel at a rate of about 6 microns per day,
      about half the corresponding rate in the rat. In spite of this, the mouse
      mandibular incisor has a relatively thick layer of enamel, since the ameloblasts
      spend a relatively long time in the zone of enamel secretion due to a fairly slow
      eruption rate.

PMID- 8886955
TI  - Immunohistochemical and ultrastructural analysis of an extracellular matrix bound
      antigen preferentially associated with mucosal postcapillary venules.
AB  - Human lymphoma derived monoclonal antibody (anti "mucosal vessel associated
      antigen' [MVAA]) binds to high endothelial venules (HEV) in gut-associated
      lymphoid tissue, but shows only weak reactivity with HEV in peripheral lymphoid
      tissues. We have used immunohistochemistry and immunoelectron microscopy to
      define the precise ultrastructural distribution of the molecule, and to determine
      whether there is any association between this molecule and cellular traffic. We
      have observed that MVAA is a component of basement membrane which is only
      expressed by a subset of blood vessels. Although it is restricted to vessels
      which support lymphocyte traffic within lymphoid tissue, we did not observe any
      association between the distribution of MVAA and extravasating lymphocytes. MVAA
      is expressed in the fetal intestine in association with a subset of larger
      vessels. It is therefore not necessarily induced as a consequence of antigenic
      challenge. It is likely that MVAA has a structural role related to its restricted
      microanatomical distribution; possibly the maintenance of integrity of vessel
      walls which are continuously disrupted by the extravasation of lymphocytes.

PMID- 8886956
TI  - Incidence and structure of the appendices of the testis and epididymis.
AB  - In paired tests obtained from 425 adults, 50 children and 10 neonates, the
      incidence of testicular appendices was 76% in adults (93.3% sessile) and 83.3% in
      neonates/children (88% sessile). An epididymal appendix was present in 21.9% of
      adults and 20% of neonates/children, out of which 79% were stalked in both types
      of specimen. Three sessile testicular appendices and 11 epididymal appendices
      were double. The microscopic structure of the appendices and the ultrastructure
      of their epithelia are described. Testicular or epididymal appendices were not
      present in any domestic or laboratory animal examined except the horse.

PMID- 8886957
TI  - The composition and central projections of the internal auricular nerves of the
      dog.
AB  - The cranial components and central terminations of the sensory nerves supplying
      the concave surface of the puppy's pinna, namely, the rostral, middle and caudal
      internal auricular nerves (RIAN, MIAN and CIAN) were investigated using
      horseradish peroxidase retrograde and transganglionic labelling techniques. All
      the 3 internal auricular nerves received contributions from the vagus. The RIAN
      received additional fibres from the trigeminal nerve while the MIAN and CIAN
      contained fibres derived from the facial nerves. In the brainstem, collaterals
      from the descending fibres of the afferents were given off at all levels to the
      medially located spinal trigeminal nucleus (SpV) which extended rostocaudally
      from the principal nucleus of the trigeminal nerve, subnuclei oralis,
      interpolaris and caudalis of the SpV to C1 or C2 cervical segment. The greatest
      density of central projections was observed in the subnucleus caudalis and C1. In
      the latter, the terminal field in the dorsal horn was roughly wedge-shaped,
      tapering off medially from lamina I towards lamina V. A somatotopic organisation
      was observed in the spinal trigeminal tract (SpVtr) and spinal trigeminal nucleus
      (SpV) in which the projection fibres and terminal fields of the RIAN were located
      lateral to those of the MIAN and CIAN. Some nontrigeminal nuclei, e.g.
      paratrigeminal and cuneate nuclei, nucleus X and the nucleus of the solitary
      tract were also labelled following HRP application to the internal auricular
      nerves. The localisation of the central projections of the internal auricular
      nerves as well as the 2nd order neurons in some specific nuclei to which the
      afferent fibres project is consistent with the concept of a brainstem
      somatovisceral link.

PMID- 8886958
TI  - Spatial relationship of lectin-labelled extracellular matrix and glutamine
      synthetase-immunoreactive astrocytes in rat cortical forebrain regions.
AB  - Extracellular matrix proteoglycans have previously been revealed by
      immunocytochemical and lectin-histochemical methods as distinct perineuronal nets
      in the microenvironment of different types of neurons, but also as a diffuse
      stain throughout the neuropil in region-dependent patterns. Ultrastructural
      investigations of perineuronal nets in subcortical regions have demonstrated
      glycan components in the close vicinity of astrocyte processes, suggesting that
      the extracellular matrix contributes differentially to the glianeuron interface.
      In the present study the spatial relationship of extracellular matrix components
      and astrocytes was characterised at the regional and cellular level by lectin
      histochemistry (soybean agglutinin, Vicia villosa agglutinin, Wisteria floribunda
      agglutinin) and antiglutamine synthetase immunocytochemistry in the rat neocortex
      and hippocampus. In most cortical areas layer-specific patterns of diffuse
      neuropil staining revealed by the lectins could also be recognised after
      glutamine synthetase (GS) immunostaining. In double-labelling experiments GS
      immunoreactive astrocyte processes were found to reach lectin-stained
      perineuronal nets. GS-immunoreactivity was often parallelled but did not coincide
      with the lectin label completely, but was observed to form net-like structures
      similar to the perineuronal lectin staining. Using immunocytochemistry with anti
      GS perineuronal, net-like structures were demonstrated on certain parvalbumin
      immunopositive neurons which are known to be ensheathed by lectin-stained
      perineuronal nets. It was evident that a single neuron may receive net-like
      contacts from several astrocytes and that a single astrocyte can contribute to
      perineuronal nets on more than one neuron. The findings support the view that N
      acetylgalactosamine-containing extracellular matrix molecules and astrocytic
      processes are topically associated to a high degree. Different proportions of
      both components may specify the individual neuronal micro-environment.

PMID- 8886959
TI  - The ontogeny of adhesion molecules expressed on the vascular endothelium of the
      developing human skin.
AB  - One of the important functions of adhesion molecules is to regulate the
      trafficking of lymphocytes and other leucocytes between the different organs and
      tissues of the body. These molecules are expressed on both the endothelial cells
      and the leucocytes, enabling them to adhere to one another and ultimately lead to
      extravasation of the leucocytes from the circulation into the surrounding tissue.
      P and E-selectin promote 'rolling' of leucocytes along the blood vessel walls,
      whereas ICAM-1 and VCAM-1 mediate subsequent firm adhesion, thus committing the
      leucocytes to extravasation. We have investigated the expression of the above
      endothelial adhesion molecules in relation to the developing dermal vasculature
      of fetal skin using histology and immunocytochemistry. This study showed that
      already at 11 wk of gestation some dermal vessels expressed P-selectin and ICAM
      1. However, by 18 wk these molecules were identified on a significant number of
      vessels, including small capillaries supplying the forming dermal pegs. In
      contrast, E-selectin and VCAM-1 molecules were rarely seen in all specimens
      examined. Our results show that even at 11 wk of gestation, the fetal skin has a
      mechanism in place for circulating leucocytes to extravasate and provide
      primitive immunosurveillance. Furthermore, the similarities between the
      distribution of P-selectin and ICAM-1 in the 18 wk fetal skin and in the normal
      adult skin were striking. These findings may shed light on our understanding of
      how the fetus detects and reacts to infections and may, in the future, lead to
      advances in the management of some intrauterine infections.

PMID- 8886960
TI  - The role of microtubules and microtubule-organising centres during the migration
      of mitochondria.
AB  - The translocation of mitochondria towards the primitive inner segment of the
      cones in the tree shrew Tupaia belangeri was investigated by transmission
      electron microscopy. Throughout ontogeny the migrating mitochondria were
      codistributed with cytoplasmic microtubules which were preserved after the
      application of conventional preparation techniques for transmission electron
      microscopy. Both the basal body of the connecting cilium and the second centriole
      located in the vicinity of the basal body were demonstrated to act as microtubule
      organising centres (MTOCs) from which axonemal and cytoplasmic microtubules
      originated. The megamitochondria in the inner segment of the retinal cones of
      Tupaia are unique among mammals with respect to their extraordinary size and to
      their ordered distribution characterised by longitudinal and radial size
      gradients within developing and mature cone inner segments. Thus the consistent
      finding of microtubules and MTOCs in the structurally polarised cones represents
      an extreme example of the capacity of cells to regulate the transport and
      distribution of organelles.

PMID- 8886961
TI  - Testis development in the opossum Monodelphis domestica.
AB  - Testis development in the grey short-tailed opossum, Monodelphis domestica, was
      investigated by light and electron microscopy in 180 animals. On the day of
      birth, half the karyotyped males were found to have histologically differentiated
      testes. By day (d) 1 testicular cords were clearly distinguished in all XY gonads
      and the tunica albuginea was fully developed. At this stage the large and pale
      primordial germ cells could be differentiated from dark pre-Sertoli cells. From d
      3 the testis became progressively rounded and testicular cords were surrounded by
      peritubular cells. Leydig cells were then distinguishable by the expected
      ultrastructural features of steroidogenically active cells, showing abundant
      vesicles of SER, extensive mitochondria with tubular cristae and numerous lipid
      inclusions. Subsequently these cells formed clusters and were surrounded by
      envelope cells until wk 12. Testes were located in the abdomen, attached to the
      large mesonephroi, until d 24 after birth when they began their descent to the
      scrotal sac. From 7 wk the interstitial tissue became less cellular. At the
      prepubertal stage (12 wk), the seminiferous tubules lacked lumina. Leydig cell
      cytoplasm was electron-dense with increased amounts of SER forming parallel
      profiles. By 4 mo (pubertal stage), seminiferous tubules were patent and various
      spermatogenic stages, including spermatozoa, were seen for the first time. Leydig
      cells then greatly outnumbered other interstitial tissue cells and were closely
      packed around blood vessels but no longer clustered by envelope cells; their SER
      was very highly organised into masses of parallel arrays and lipid inclusions
      were reduced. In the adult (1 y) Leydig cells reached their greatest size; their
      morphological features resembled those seen at 4 mo except that lipid inclusions
      were sparse. In ageing Leydig cells (2-3 y), large amounts of SER were present
      but disorganised.

PMID- 8886962
TI  - Ontogeny of four blood-brain barrier markers: an immunocytochemical comparison of
      pial and cerebral cortical microvessels.
AB  - Pial and cortical microvessels possess many blood-brain barrier (BBB) properties
      in common, including impermeability to electron dense tracers, high
      transendothelial electrical resistance and specialised endothelial cell
      ultrastructural features. To compare pial and cortical microvessels further, a
      developmental, immunocytochemical study was undertaken of 4 BBB markers in the
      rat: OX-47, EBA, GLUT-1 and s-laminin. The appearance of the markers was
      monitored from embryonic d 16, to postnatal and adult stages. Each of the 4
      markers appeared simultaneously in both pial and cortical vessels. GLUT-1 and OX
      47 were present in endothelial cells of the BBB from E 16 to the adult. EBA and s
      laminin appeared from postnatal d 7 through to the adult. Pial microvessels lack
      the ensheathment of astrocytes which may be involved in the induction and/or
      maintenance of BBB markers in the cortex. It is possible that astrocyte-derived
      factors diffusing from the brain surface are responsible for induction of BBB
      properties in the pial microvessels.

PMID- 8886963
TI  - Ultrastructure of the human spinal arachnoid mater and dura mater.
AB  - Human spinal dura and arachnoid, obtained during neurosurgical operations, were
      studied by transmission electron microscopy. The ultrastructure of spinal
      meninges largely conformed to the morphology of the cranial meninges, but some
      minor differences were detected. The dura was composed of an outermost loosely
      arranged fibroelastic layer, a middle basically fibrous portion and an innermost
      cellular layer (dural border cell layer). The dural border cell layer was
      characterised by multiple interdigitating cell processes, no extracellular
      collagen, significant extracellular spaces and few cell junctions. Paravascular
      vesiculated nerve profiles were encountered within the fibroadipose epidural
      tissue. The arachnoid was composed of an outermost portion (arachnoid barrier
      cell layer), presenting tightly packed cells, numerous tight junctions and no
      extracellular collagen. In view of its numerous tight junctions, the arachnoid
      barrier cell layer is considered to represent an effective morphological and
      physiological meningeal barrier between the cerebrospinal fluid in the
      subarachnoid space and the blood circulation in the dura. The arachnoid barrier
      layer was always characterised by a distinct continuous basal lamina on its inner
      surface towards the innermost collagenous portion of the arachnoid (arachnoid
      reticular cell layer). The interweaving arachnoid trabecular cells within this
      layer possessed numerous mitochondria and were anchored to the inner surface of
      the arachnoid barrier cell layer by desmosomes. An additional layer of flattened
      branching cells was demonstrated along the inner surface of the arachnoid
      reticular cell layer and assumed to be an "arachnoid border cell layer'.
      Morphological data suggest that the dura and arachnoid closely adhere at spinal
      levels in man without any naturally occurring "subdural space'. However,
      structurally, the dural border cell layer forms a weak cell layer at the dura
      arachnoid continuum that is easily disrupted. The creation of an artifactual
      subdural space at spinal levels is discussed.

PMID- 8886964
TI  - The blood supply of the human temporalis muscle: a vascular corrosion cast study.
AB  - Knowledge as to the blood supply of the human temporalis muscle is limited to its
      extramuscular path and relations, little information existing about the
      intramuscular vascular architecture. To investigate the 3-dimensional vascular
      network in the human temporalis muscle, in 5 fresh cadavers an infusion of
      methylmethacrylate resin was made via the carotid vessels with subsequent removal
      of the organic tissues by a corrosion process. The vascular corrosion casts of
      the temporalis muscle were studied by stereomicroscopy and scanning electron
      microscopy. In 6 well perfused muscle specimens, the temporalis muscle was found
      to be consistently supplied by 3 arteries: the anterior and posterior deep
      temporal arteries, and the middle temporal artery. Each primary artery branched
      into the secondary arterioles and then terminal arterioles. The venous network
      accompanied the arteries, and double veins pairing a single artery was a common
      finding. Arteriovenous anastomosis was absent, whereas arterioarterial and
      venovenous anastomoses were common. The capillaries formed a dense interlacing
      network with an orientation along the muscle fibres. Understanding of the
      intramuscular angioarchitecture of the temporalis provides the vascular basis for
      surgical flap manipulation and splitting design.

PMID- 8886965
TI  - Morphology and histochemistry of a PAS-positive granular cell in the gills of the
      gilthead seabream, Sparus aurata L.
AB  - A periodic acid-Schiff-positive granular cell (PAS-G cell) was investigated by
      light and electron microscopy in the gills of the gilthead seabream (Sparus
      aurata L.). Despite the use of several fixatives, it was only possible to
      demonstrate metachromasia after fixing these cells with a solution of 10% formol
      and 5% acetic acid in methanol. Using this fixative, their granules stained
      purple with toluidine blue or thionin. In semithin resin sections, the granules
      also stained purple with toluidine blue-borax. Ultrastructurally, these cells
      possessed 2 types of homogeneous electron-dense granules and characteristic long
      thin surface processes resembling a string of beads. These PAS-G cell share
      morphological features with basophils and mast cells, and were metachromatic.
      They were observed in sites similar to those for mast cells in mammals.

PMID- 8886966
TI  - Morphometric studies of the muscular branch of the median nerve.
AB  - The branch from the median nerve to the thenar muscles has a proximal and lateral
      (recurrent) course and is vulnerable to lesions that affect these muscles.
      Because of its anatomical-clinical importance, this branch was studied in 60
      palmar regions from 30 cadavers of adult individuals of both sexes, aged between
      23 and 77 y. It arose from the lateral branch of the median nerve in 83.3% of the
      cases. Its origin was distal to the flexor retinaculum in 48.3%, at the distal
      margin of the retinaculum in 31.6%, in the carpal tunnel in 18.3% and proximal to
      the retinaculum in 1.7%; it pierced the retinaculum in 15%. The point of
      recurrence of the branch was localised topographically to 34.6 +/- 3.6 mm from
      the distal wrist crease; the angle between its recurrent course and the
      longitudinal axis of the hand averaged 66.8 degrees. In 50% of the cases the
      muscular branch innervated abductor pollicis brevis (APB), opponens pollicis (OP)
      and the superficial head of flexor pollicis brevis (FPB), in 40% it supplied only
      APB and OP, and in 10% a short muscular branch gave rise to independent branches
      in the palm and which supplied APB, OP and the superficial head of FPB. The so
      called "accessory thenar branch' was found in 38.3%.

PMID- 8886967
TI  - Chicken myosin IB mRNA is highly expressed in lymphoid tissues.
AB  - Little is known about the functions of members of the myosin I family in
      vertebrates. Chicken myosin IB is a member of the amoeba-type subclass of myosin
      I molecules and tissue localisation studies may provide possible clues to the
      functions of these myosin I molecules. The expression of the mRNA of this
      unconventional myosin IB was analysed by in situ hybridization and compared with
      that of the well characterised brush border myosin I on frozen sections of
      tissues from the adult domestic chicken. High levels of myosin IB mRNA were found
      in the intestine and spleen, but were not found in other tissues examined such as
      brain, heart, lung, liver and kidney. In the intestine, myosin IB mRNA was much
      more abundant in the lamina propria than in the enterocytes, whereas brush border
      myosin I mRNA was restricted to the enterocytes. In the spleen, myosin IB mRNA
      expression was abundant in regions of white pulp, namely germinal centres,
      periellipsoid lymphocyte sheaths and periarteriolar lymphocyte sheaths.
      Lymphocytes are the major cell type in both the lamina propria and the white pulp
      of the spleen, which suggests that chicken myosin IB is highly expressed in
      lymphocytes. Lymphocyte recirculation depends on their migration through the
      endothelial layer and it is possible that myosin IB may have a role to play in
      this type of cell motility.

PMID- 8886968
TI  - Case report: bilateral location of the axillary artery posterior to the medial
      cord of the brachial plexus.

PMID- 8886969
TI  - An accessory foramen deep in the infraorbital fissure.

PMID- 8886970
TI  - A different approach to tumour suppression. The Alexandra Kefalides Memorial
      Lecture.
AB  - When tumour cells are fused with normal ones, malignancy is suppressed. It has
      been shown that this suppression is associated with the imposition on the hybrid
      cell of the terminal differentiation programme of the normal parent cell. We
      report here the consequences of imposing the synthesis of keratin 1 and keratin
      10, markers of terminal differentiation in the epidermal keratinocyte, on
      malignant cells of keratinocyte and non-keratinocyte lineage. We find that there
      is extreme selection in vivo against cells making keratin 1: tumours arising from
      inocula of such cells are invariably produced by the selective overgrowth of
      cells in which keratin 1 synthesis has been drastically reduced, usually to trace
      levels. No such selection operates against keratin 10. It is possible that if
      substantial synthesis of keratin 1 could be induced in malignant cells in a
      clinical context, some therapeutic benefit might accrue.

PMID- 8886971
TI  - Epigenetic control of mammalian centromere protein binding: does DNA methylation
      have a role?
AB  - Chromosome 1 of the inbred mouse strain DBA/2 has a polymorphism associated with
      the minor satellite DNA at its centromere. The more terminal block of satellite
      DNA sequences on this chromosome acts as the centromere as shown by the binding
      of CREST ACA serum, anti-CENP-B and anti-CENP-E polyclonal sera. Demethylation of
      the minor satellite DNA sequences accomplished by growing cells in the presence
      of the drug 5-aza-2'-deoxycytidine results in a redistribution of the CENP-B
      protein. This protein now binds to an enlarged area on the more terminal block
      and in addition it now binds to the more internal block of minor satellite DNA
      sequences on chromosome 1. The binding of the CENP-E protein does not appear to
      be affected by demethylation of the minor satellite sequences. We present a model
      to explain these observations. This model may also indicate the mechanism by
      which the CENP-B protein recognises specific sites within the arrays of minor
      satellite DNA on mouse chromosomes.

PMID- 8886972
TI  - TGF beta 1 promotes actin cytoskeleton reorganization and migratory phenotype in
      epithelial tracheal cells in primary culture.
AB  - In the present study we have investigated the effects of transforming growth
      factor beta (TGF beta 1) on rabbit tracheal epithelial cells in primary culture,
      with respect to cell proliferation and differentiation. Epithelial tracheal cells
      derived from an explant plated on an extracellular matrix, formed an outgrowth
      resulting from cell division and cell migration. TGF beta 1 treatment produced a
      negative effect on cell proliferation, but in contrast, promoted a marked
      enhancement of cell migration and increase in outgrowth surface. TGF beta 1
      induced marked cell shape changes, including cell spreading and lack of
      stratification, associated with reduced cell-cell contacts and increased cell
      substratum anchorage, as seen by electron microscopic observations.
      Immunocytological studies demonstrated major TGF beta 1-induced actin
      cytoskeleton reorganization, corresponding to the development of a basal stress
      fiber network and decrease of the annular cell border, without affecting the
      tight junctions. The migratory phenotype was approached by microcinematography
      which clearly showed that TGF beta 1 triggered a stimulatory effect on migration
      of epithelial cells, determined using an image analyzing system. Present findings
      suggest a beneficial role for TGF beta 1 during wound healing in providing the
      acquisition of a migratory phenotype, with a higher capacity to migrate either on
      collagen or on different extracellular matrix components including laminin and
      fibronectin. Conversely, present data are not consistent with a squamous response
      to TGF beta 1, since metaplastic differentiation did not occur, as characterized
      by cytokeratin expression and cross-linked envelopes formation.

PMID- 8886973
TI  - Chromatin organization in the homogeneously staining regions of a methotrexate
      resistant mouse cell line: interspersion of inactive and active chromatin domains
      distinguished by acetylation of histone H4.
AB  - We have analyzed the organization of the homogeneously staining regions (HSRs) in
      chromosomes from a methotrexate-resistant mouse melanoma cell line. Fluorescence
      in situ hybridization techniques were used to localize satellite DNA sequences
      and the amplified copies of the dihydrofolate reductase (DHFR) gene that confer
      drug-resistance, in combination with immunofluorescence using antibody probes to
      differentiate chromatin structure. We show that the major DNA species contained
      in the HSRs is mouse major satellite, confirming previous reports, and that this
      is interspersed with DHFR DNA in an alternating tandem array that can be resolved
      at the cytological level. Mouse minor satellite DNA, which is normally located at
      centromeres, is also distributed along the HSRs, but does not appear to interfere
      with centromere function. The blocks of major satellite DNA are coincident with
      chromatin domains that are labelled by an autoantibody that recognizes a
      mammalian homologue of Drosophila heterochromatin-associated protein 1, shown
      previously to be confined to centric heterochromatin in mouse. An antiserum that
      specifically recognizes acetylated histone H4, a marker for active chromatin,
      fails to bind to the satellite DNA domains, but labels the intervening segments
      containing DHFR DNA. We can find no evidence for the spreading of the inactive
      chromatin domains into adjacent active chromatin, even after extended passaging
      of cells in the absence of methotrexate selection.

PMID- 8886974
TI  - The spacer protein Spc110p targets calmodulin to the central plaque of the yeast
      spindle pole body.
AB  - Yeast calmodulin (CaM) was found to be localized to the microtubule organizing
      centre, the spindle pole body. The spindle pole body is a multi-layered structure
      consisting of outer, central and inner plaques. In this paper, we report that a
      fraction of CaM is in association with the central plaque of the spindle pole
      body. This localization is dependent on the calmodulin-binding site of another
      spindle pole body component, Spc110p, which serves as a spacer connecting the
      inner plaque with the central plaque. Since the CaM-binding site of Spc110p is
      located near the carboxy terminus, Spc110p-dependent localization of calmodulin
      defines the orientation of Spc110p with the carboxy terminus towards the central
      plaque and the amino terminus towards the inner plaque. This orientation of
      Spc110p was confirmed using antibodies specific for the amino-terminal end of
      Spc110p, which predominantly labelled the inner plaque. In addition, synthetic
      peptides corresponding to the calmodulin-binding site of Spc110p bound to
      calmodulin with a Kd in the nanomolar range and nearly independent of Ca2+.

PMID- 8886975
TI  - Location of the HIV-1 Rev protein during mitosis: inactivation of the nuclear
      export signal alters the pathway for postmitotic reentry into nucleoli.
AB  - The HIV-1 Rev protein localizes predominantly to the nucleolus of HIV-1-infected
      or Rev-expressing cells. The subcellular location of Rev during mitotic nucleolar
      disintegration was examined at various stages of mitosis in synchronized Rev
      expressing CMT3 cells. During early prophase Rev was predominantly located in
      disintegrating nucleoli and began to accumulate at the peripheral regions of
      chromosomes in late prophase, eventually distributing uniformly on all
      chromosomes in prometaphase. In anaphase Rev remained associated with the
      perichromosomal regions, but significant amounts of Rev were also seen in
      numerous nucleolus-derived foci. The movement of Rev from disintegrating nucleoli
      to perichromosomal regions and foci was similar to that of nonribosomal nucleolar
      proteins, including fibrillarin, nucleolin, protein B23 and p52 of the granular
      component. During telophase Rev remained associated with perichromosomal regions
      and mitotic foci until the nuclear envelope started to reform. When nuclear
      envelope formation was complete in late telophase, nonribosomal nucleolar
      proteins were present in prenucleolar bodies (PNBs) which were eventually
      incorporated into nucleoli; at the same time, Rev was excluded from nuclei. In
      contrast, a trans-dominant negative Rev protein containing an inactive nuclear
      export signal reentered nuclei by the nonribosomal nucleolar protein pathway in
      late telophase, associating with PNBs and reformed nucleoli. Rev protein reentry
      into postmitotic nuclei was delayed until early G1 phase, but before the arrival
      of ribosomal protein S6. Thus, Rev behaves like a nonribosomal nucleolar protein
      through mitosis until early telophase; however, its nuclear reentry seems to
      require reestablishment of both a nuclear import system and active nucleoli.

PMID- 8886976
TI  - Molecular characterization of mitofilin (HMP), a mitochondria-associated protein
      with predicted coiled coil and intermembrane space targeting domains.
AB  - We have identified and characterized a human protein of the mitochondria which we
      call mitofilin. Using monoclonal and polyclonal antibodies, we have isolated cDNA
      clones and characterized mitofilin biochemically. It appears as a 90 and 91 kDa
      doublet in western blots and is translated from a single 2.7 kb mRNA. Antibodies
      raised against cellular and bacterially-expressed protein given identical
      cytoplasmic immunofluorescence and immunoblot results. Mitofilin co-localizes
      with mitochondria in immunofluorescence experiments and co-purifies with
      mitochondria. Double label studies show co-localization only with mitochondria
      and not with Golgi or endoplasmic reticulum. Co-localization with mitochondria is
      retained when actin or tubulin are de-polymerized, and mitofilin is expressed in
      all human cell types tested. The cDNA encodes a polypeptide with a central alpha
      helical region with predicted coiled coil domains flanked by globular amino and
      carboxy termini. Unlike coiled coil motor proteins, mitofilin is resistant to
      detergent extraction. The presence of mitochondrial targeting and stop-transfer
      sequences, along with the accessibility of mitofilin to limited proteolysis
      suggests that it resides predominantly in the intermembrane space, consistent
      with immuno-electron micrographs which show mitofilin mainly at the mitochondrial
      periphery. The cDNA sequence of mitofilin is identical to that recently reported
      by Icho et al. (1994; Gene 144, 301-306) for a mRNA preferentially expressed in
      heart muscle (HMP), consistent with the high levels of mitochondria in cardiac
      myocytes.

PMID- 8886977
TI  - Expression, localization and functional role of small GTPases of the Rab3 family
      in insulin-secreting cells.
AB  - We examined the presence of small molecular mass GTP-binding proteins of the Rab3
      family in different insulin-secreting cells. Rab3B and Rab3C were identified by
      western blotting in rat and in human pancreatic islets, in two rat insulin
      secreting cell lines, RINm5F and INS-1, as well as in the hamster cell line HIT
      T15. In contrast, Rab3A was detected in rat pancreatic islets as well as in the
      two insulin-secreting rat cell lines but not in human pancreatic islets and was
      only barely discernible in HIT-T15 cells. These findings were confirmed by two
      dimensional gel electrophoresis followed by GTP-overlay of homogenates of
      pancreatic islets and of the purified protein. Northern blotting analysis
      revealed that Rab3D is expressed in the same insulin-secreting cells as Rab3A.
      Separation of the cells of the rat islets by fluorescence-activated cell sorting
      demonstrated that Rab3A was exclusively expressed in beta-cells. Rab3A was found
      to be associated with insulin-containing secretory granules both by
      immunofluorescence, immunoelectron microscopy and after sucrose density gradient.
      Overexpression in HIT-T15 cells of a Rab3A mutant deficient in GTP hydrolysis
      inhibited insulin secretion stimulated by a mixture of nutrients and bombesin.
      Insulin release triggered by these secretagogues was also slightly decreased by
      the overexpression of wild-type Rab3A but not by the overexpression of wild-type
      Rab5A and of a Rab5A mutant deficient in GTP hydrolysis. Finally, we studied the
      expression in insulin-secreting cells of rabphilin-3A, a putative effector
      protein that associates with the GTP-bound form of Rab3A. This Rab3A effector was
      not detectable in any of the cells investigated in the present study. Taken
      together these results indicate an involvement of Rab3A in the control of insulin
      release in rat and hamster. In human beta-cells, a different Rab3 isoform but
      with homologous function may replace Rab3A.

PMID- 8886978
TI  - Nuclear lamina and nuclear matrix organization in sperm pronuclei assembled in
      Xenopus egg extract.
AB  - Nuclear lamina and matrices were prepared from sperm pronuclei assembled in
      Xenopus egg extracts using a fractionation and extraction procedure. Indirect
      immunofluorescence revealed that while chromatin was efficiently removed from
      nuclei during the extraction procedure, the distribution of lamins was
      unaffected. Consistent with this data, the amount of lamin B3, determined by
      immunoblotting, was not affected through the extraction procedure. Nuclear
      matrices were visualised in DGD sections by TEM. Within these sections filaments
      were observed both at the boundary of the nucleus (the lamina) and within the
      body of the nucleus (internal nuclear matrix filaments). To improve resolution,
      nuclear matrices were also prepared as whole mounts and viewed using field
      emission in lens scanning electron microscopy (FEISEM). This technique revealed
      two distinct networks of filaments. Filaments lying at the surface of nuclear
      matrices interconnected nuclear pores. These filaments were readily labelled with
      monoclonal anti-lamin B3 antibodies. Filaments lying within the body of the
      nuclear matrix were highly branched but were not readily labelled with antilamin
      B3 antibodies. Nuclear matrices were also prepared from sperm pronuclei assembled
      in lamin B3 depleted extracts. Using FEISEM, filaments were also detected in
      these preparations. However, these filaments were poorly organised and often
      appeared to aggregate. To confirm these results nuclear matrices were also
      observed as whole mounts using TEM. Nuclear matrices prepared from control nuclei
      contained a dense array of interconnected filaments. Many (but not all) of these
      filaments were labelled with anti-lamin B3 antibodies. In contrast, nuclear
      matrices prepared from "lamin depleted nuclei' contained poorly organised or
      aggregated filaments which were not specifically labelled with anti-lamin B3
      antibodies.

PMID- 8886979
TI  - Occludin is a functional component of the tight junction.
AB  - Occludin's role in mammalian tight junction activity was examined by 'labeling'
      the occludin pool with immunologically detectable chick occludin. This was
      accomplished by first transfecting MDCK cell with the Lac repressor gene. HygR
      clones were then transfected with chick occludin cDNA inserted into a Lac
      operator construct. The resulting HygR/NeoR clones were plated on porous inserts
      and allowed to form tight junctions. Once steady state transepithelial electrical
      resistance was achieved, isopropyl- beta-D-thiogalactoside was added to induce
      chick occludin expression. Confocal laser scanning microscopy of monolayers
      immunolabeled with Oc-2 monoclonal antibody revealed that chick occludin
      localized precisely to the preformed tight junctions. When sparse cultures were
      maintained in low Ca2+ medium, chick occludin and canine ZO-1 co-localized to
      punctate sites in the cytoplasm suggesting their association within the same
      vesicular structures. In low calcium medium both proteins also co-localized to
      contact sites between occasional cell pairs, where a prominent bar was formed at
      the plasma membrane. Chick occludin was detectable by western blot within two
      hours of adding isopropyl- beta-D-thiogalactoside to monolayers that had
      previously achieved steady state transepithelial electrical resistance; this
      coincided with focal immunofluorescence staining for chick occludin at the cell
      membrane of some cells. A gradual rise in transepithelial electrical resistance,
      above control steady state values, began five hours after addition of the
      inducing agent reaching new steady state values, which were 30-40% above
      baseline, 31 hours later. Upon removal of isopropyl- beta-D-thiogalactoside chick
      occludin expression declined slowly until it was no longer detected in western
      blots 72 hours later; transepithelial electrical resistance also returned to
      baseline values during this time. While densitometric analysis of western blots
      indicated that the presence of chick occludin had no detectable effect on E
      cadherin or ZO-1 expression, the possibility cannot be excluded that ZO-1 might
      be a limiting factor in the expression of chick occludin at the cell surface. To
      test whether expression of chick occludin affected the process of tight junction
      assembly, monolayers in low Ca2+ medium were treated with isopropyl- beta-D
      thiogalactoside for 24 or 48 hours, before Ca2+ was added to stimulate tight
      junction assembly. Chick occludin did not alter the rate at which transepithelial
      electrical resistance developed, however, steady state values were 30-40% above
      control monolayers not supplemented with the inducing agent. By freeze fracture
      analysis, the number of parallel tight junction strands shifted from a mode of
      three in controls to four strands in cells expressing chick occludin and the mean
      width of the tight junction network increased from 175 +/- 11 nm to 248 +/- 16
      nm. Two days after plating confluent monolayers that were induced to express
      chick occludin, mannitol flux was reduced to a variable degree relative to
      control monolayers. With continued incubation with the inducing agent, mannitol
      flux increased on day 11 to 50%, and TER rose to 45% above controls. Both of
      these changes were reversible upon removal of isopropyl- beta-D-thiogalactoside.
      These data are consistent with the notion that occludin contributes to the
      electrical barrier function of the tight junction and possibly to the formation
      of aqueous pores within tight junction strands.

PMID- 8886980
TI  - N-tropomodulin: a novel isoform of tropomodulin identified as the major binding
      protein to brain tropomyosin.
AB  - We have identified and characterized two proteins in rat brain that bind to the
      neuron-specific tropomyosin isoform, TMBr3. The two proteins were identified by
      blot overlay assay, in which the proteins immobilized on the membrane were probed
      by epitope-tagged TMBr3, followed by detection with anti-epitope antibody. We
      have purified these proteins using a TMBr3 affinity column. Peptide sequencing as
      well as immunoblotting showed that one of the two proteins is identical to
      tropomodulin, a tropomyosin-binding protein originally identified in
      erythrocytes. The cDNA for the other protein was cloned from an adult rat brain
      cDNA library using degenerate oligonucleotides that we designed based on the
      peptide sequences. Sequence analysis of the cDNA clone revealed this protein to
      be a novel isoform of tropomodulin which is the product of a distinct gene, and
      is herein referred to as N-tropomodulin. Recombinant N-tropomodulin bound to
      TMBr3 as well as to other low molecular mass tropomyosins (TM5a or TM5), but not
      to high molecular mass tropomyosins (TM2 or TMBr1). Northern blotting and RNase
      protection assays as well as immunoblotting showed that N-tropomodulin is
      expressed predominantly in brain. Furthermore, RNase protection assays revealed
      no alternatively spliced regions within the coding sequence. Developmentally, N
      tropomodulin was detected in rat brain as early as embryonic day 14 and reaches
      the adult level before birth. Immunofluorescence of primary frontal cortex cell
      cultures showed that N-tropomodulin is specifically expressed in neurons. The
      neuron-specific expression of N-tropomodulin strongly suggests specialized roles
      of this TM-binding protein in neurons.

PMID- 8886981
TI  - Putative GTPase Gtr1p genetically interacts with the RanGTPase cycle in
      Saccharomyces cerevisiae.
AB  - In order to identify a protein interacting with RCC1, a guanine nucleotide
      exchange factor for the nuclear GTPase Ran, we isolated a series of cold
      sensitive suppressors of mtr1-2, a temperature-sensitive mutant of the
      Saccharomyces cerevisiae RCC1 homologue. One of the isolated suppressor mutants
      was mutated in the putative GTPase Gtr1p, being designated as gtr1-11. It also
      suppressed other alleles of mtr1-2, srm1-1 and prp20-1 in contrast to
      overexpression of the S. cerevisiae Ran/TC4 homologue Gsp1p, previously reported
      to suppress prp20-1, but not mtr1-2 or srm1-1. Furthermore, gtr1-11 suppressed
      the rna1-1, temperature-sensitive mutant of the Gsp1p GTPase-activating protein,
      but not the srp1-31, temperature-sensitive mutant of the S. cerevisiae importin
      alpha homologue. mtr1-2, srm1-1 and prp20-1 were also suppressed by
      overexpression of the mutated Gtr1p, Gtr1-11p. In summary, Gtr1p that was
      localized in the cytoplasm by immunofluoresence staining was suggested to
      function as a negative regulator for the Ran/TC4 GTPase cycle.

PMID- 8886982
TI  - Alterations in neural intermediate filament organization: functional implications
      and the induction of pathological changes related to motor neuron disease.
AB  - The properties regulating the supramolecular organization of neural intermediate
      filament (NIF) networks have been investigated in cultured dorsal root ganglion
      (DRG) neurons. The studies described take advantage of the ability of endogenous
      NIF to incorporate purified biotinylated neurofilament triplet (NFT) proteins, NF
      L, NF-M and NF-H. When injected at concentrations of 0.8-1.0 mg/ml injection
      buffer, each of these proteins is incorporated without perturbing the endogenous
      NIF network. However, at progressively higher concentrations, NF-H induces the
      aggregation and accumulation of NIF in the cell body. Subsequent to the induction
      of these aggregates, numerous alterations in the cytoarchitecture of neurons can
      be detected. The latter occur in a temporal sequence which appears to begin with
      the fragmentation of the Golgi complex. At later times, accumulation of
      mitochondria within the proximal region of neurites, peripheralization of the
      nucleus, and a significant decrease in neurite caliber become obvious. After
      longer time periods, the NIF aggregates are seen to react with an antibody which
      reveals abnormally phosphorylated NF-H. These observations demonstrate that an
      imbalance in the normal stoichiometric relationships among the NFT proteins
      rapidly alters the supramolecular organization of the NIF network. These changes
      most likely reflect the normal functions of neurofilaments in cell shape and the
      organization and cytoplasmic distribution of membranous organelles.
      Interestingly, virtually all of these changes closely resemble those which have
      been reported in motor neuron diseases such as amyotrophic lateral sclerosis
      (ALS). These findings suggest that cultured neurons can be used as models for
      more precisely defining the relationships between the formation of NIF aggregates
      and the sequence of cytopathological events which typify neurodegenerative
      diseases.

PMID- 8886983
TI  - The fission yeast sts5+ gene is required for maintenance of growth polarity and
      functionally interacts with protein kinase C and an osmosensing MAP-kinase
      pathway.
AB  - Cell morphogenesis is a fundamental phenomenon that involves understanding a
      number of biological processes including the developmental program, polarity and
      cell division. Fission yeast sts5 mutant cells are round rather than cylindrical
      with cortical actin randomly dispersed. Genetic analyses demonstrate that the
      sts5+ gene is required for maintenance of cell shape during interphase when the
      cell normally exhibits polarised growth. The sts5 mutant is not defective in cell
      wall integrity. Deletion of ppe1+, which encodes a type 2A-like protein
      phosphatase, shows similar phenotypes to the sts5 mutant and these two mutations
      are synthetically lethal. Multicopy plasmids containing either the protein kinase
      C-like gene pck1+ or the protein tyrosine phosphatase pyp1+, an inhibitor of an
      osmosensing Sty1/Spc1 MAP-kinase, are capable of suppressing the sts5 mutation.
      Consistent with this, we have found that the wis1 mutation, which is defective in
      a MAP-kinase kinase of the pathway, suppresses the sts5 mutation. The predicted
      sts5+ gene product exhibits sequence similarity to two yeast proteins, Dis3 and
      Ssd1 and a nematode protein, F46E8.6, where the former two yeast proteins have
      been shown to be involved in cell cycle control and cell morphogenesis. The sts5+
      gene is not essential for cell viability, but is absolutely required for
      polarised growth as the gene disruption showed the same phenotypes as those of
      the original mutants. Overexpression of the sts5+ gene resulted in altered cell
      morphology and, cortical actin in these overproducing cells was also abnormal,
      fainter and often dispersed. Anti-Sts5 antibody specifically detected a 130 kDa
      protein by western blotting. A green fluorescent protein-Sts5 fusion protein
      localised in the cytoplasm with a discrete punctate pattern, suggesting that the
      Sts5 protein is a component of a novel structure. These results have indicated
      that the Sts5 protein is a crucial determinant of polarised growth and that it
      functionally interacts with the serine/threonine phosphatase, protein kinase C,
      and an osmosensing MAP-kinase to maintain cell morphology.

PMID- 8886984
TI  - Endo-exonuclease of human leukaemic cells: evidence for a role in apoptosis.
AB  - Inactive forms of endo-exonuclease, activated in vitro by treatment with trypsin,
      have been identified in human leukaemic CEM and MOLT-4 cells. They comprise over
      95% of the total single-strand DNase activity in nuclei and are mainly bound to
      chromatin and the nuclear matrix. The activated enzyme had Mg2+(Mn2+)-dependent,
      Ca(2+)-stimulated activities with single- and double-strand DNAs and RNA
      (polyriboadenylic acid) and other properties characteristic of endo-exonucleases
      previously described. At least twice as much inactive endo-exonuclease has also
      been localised in extranuclear compartments of CEM and MOLT-4 cells, 85% bound to
      the membranes of the endoplasmic reticulum and 15% free in the cytosol. The
      soluble cytosolic trypsin-activatable endo-exonuclease was immunoprecipitated by
      antibodies raised independently to both Neurospora and monkey CV-1 cell endo
      exonucleases. The free and bound enzymes of both nuclear and extranuclear
      compartments also cross-reacted on immunoblots with the antibody raised to
      Neurospora endo-exonuclease to reveal multiple polypeptides ranging in size from
      18 to 145 kDa, many of which exhibited activity on DNA gels. The major species
      bound to the chromatin/matrix were in the 55-63 kDa range. Limited proteolysis of
      the large polypeptides to those of 18 to 46 kDa accompanied spontaneous chromatin
      DNA fragmentation to form DNA "ladders' in an isolated nuclei/cytosol system.
      When the leukaemic cells were treated in culture with either etoposide or
      podophyllotoxin to induce apoptosis, the largest polypeptides disappeared and
      smaller endo-exonuclease-related polypeptides of 18 to 46 kDa were detected in
      the nuclear extracts. The appearance of these polypeptides also correlated with
      extensive chromatin DNA fragmentation. In addition, there were correlations
      between the depletion of the major 55-63 kDa species bound to the membranes of
      the endoplasmic reticulum, depletion of the extranuclear trypsin-activatable
      activity and the onset and extent of chromatin DNA fragmentation in both cell
      lines. The extranuclear 55-63 kDa species may be precursors of the
      chromatin/matrix bound endo-exonuclease. The results indicate that endo
      exonuclease plays a role in chromatin DNA degradation in mammalian cells during
      apoptosis.

PMID- 8886985
TI  - Engagement of L-selectin impairs the actin polymerizing capacity of beta 2
      integrins on neutrophils.
AB  - A sequential activation of L-selectin and beta 2-integrins on neutrophils is
      crucial for the rolling, adherence and subsequent migration of these cells on the
      endothelium. However, little is known about a possible interplay between these
      adhesion receptors in the final regulation of cell motility. The results
      presented here show that sulfatides themselves (here used as tools to activate L
      selectins), have no major effect on the cellular content of filamentous actin (F
      actin), but cause a time-related decrease in the beta 2-integrin-induced
      formation of F-actin. This effect of sulfatides was abolished in cells lacking L
      selectin as a result of pretreatment with chymotrypsin. A similar sulfatide
      induced activation of L-selectin also caused a pronounced and time-related
      decrease of a subsequent chemotactic peptide-induced F-actin response. The effect
      of sulfatides on both beta 2-integrin- and chemotactic peptide-induced F-actin
      were abolished if L-selectin were blocked by preincubating the cells with
      specific antibodies to L-selectin. These effects of L-selectin engagement on
      cellular F-actin content were neither abolished by blocking the cytosolic free
      Ca2+ signal with bis-(2-amino-5-methylphenoxy)ethane-N,N,N',N'-tetraaceticacid
      tetraacetoxymethyly ester (MAPT/AM) nor by blocking a cAMP-induced activation of
      protein kinase A by pretreating the cells with adenosine-3',5'-cyclic monophos
      phorothioate (Rp-cAMPS). Instead we found that L-selectin engagement impaired an
      early beta 2-integrin-induced tyrosine kinase activation, an event shown to be
      necessary for a normal beta 2-integrin-mediated F-actin response. The present
      demonstration of a negative feed-back function of L-selectin on beta 2-integrin
      induced modulations of the actin cytoskeleton, suggests that the relative
      distribution and/or density of the respective L-selectin and beta 2-integrin
      ligands on endothelial cells might be important factors in determining the final
      site of firm adhesion and extravasation of neutrophils.

PMID- 8886986
TI  - C-Met signalling in an HGF/SF-insensitive variant MDCK cell line with
      constitutive motile/invasive behaviour.
AB  - The Met protein is a receptor tyrosine kinase for hepatocyte growth
      factor/scatter factor (HGF/SF), a multifunctional growth factor with mitogenic,
      motogenic and morphogenic properties. A morphologically altered variant of the
      MDCK cell line, MDCK-1, spontaneously exhibits a number of features associated
      with a partial HGF/SF-Met induced phenotype (less adhesive colonies in culture,
      enhanced invasion and motility, nascent tubule formation), but paradoxically does
      not respond to HGF/SF treatment. Although the overall cell surface expression and
      distribution of Met were found to be similar in parental MDCK cells and the MDCK
      1 cell line, p145met autophosphorylation (+/ HGF/SF) was significantly reduced in
      MDCK-1 cells in vitro and in vivo when compared with parental MDCK cells. In
      contrast, EGF induced cell proliferation and EGF receptor autophosphorylation to
      similar levels in both cell lines. The basal levels of protein tyrosine
      phosphorylation were higher in MDCK-1 cells when compared with parental MDCK
      cells, including that of two prominent proteins with molecular masses of
      approximately 185 kDa and 220 kDa. Moreover, both p185 and p220 are present and
      tyrosine phosphorylated in Met immunoprecipitates from MDCK-1 cells (+/-HGF/SF),
      but not parental MDCK cells. In addition, Met immunocomplexes from MDCK-1 cells
      exhibited an approximately 3-fold increased tyrosine kinase activity in vitro
      when compared with MDCK cells, correlating with the higher basal levels of total
      phosphotyrosine. Treatment of MDCK-1 cells with the tyrosine kinase inhibitor
      herbimycin A reverted the cell phenotype to a more MDCK-like morphology in
      culture, with a concomitant reduction in the tyrosine phosphorylation
      predominantly of p220. Taken together these data suggest that aberrations in Met
      activity and associated signalling render MDCK-1 cells insensitive to HGF/SF, and
      may also mediate alterations in MDCK-1 cell behaviour.

PMID- 8886987
TI  - Quality control in protein biogenesis: thiol-mediated retention monitors the
      redox state of proteins in the endoplasmic reticulum.
AB  - There is accumulating evidence that proteins can be retained in the endoplasmic
      reticulum by a mechanism that is believed to monitor the oxidation status of one
      or more cysteines in their sequences. For example, a single cysteine residue
      critical for retention of secretory IgM assembly intermediates has been mapped to
      the C-terminal cysteine, Cys575, of the secretory mu chain. Little is known
      concerning the mechanism responsible for this system of quality control, which
      has been termed thiolmediated retention. In particular, it is not known if the
      mechanism monitors the redox state of the important cysteine residue in the
      secretory mu protein itself or within the context of higher-order IgM complexes.
      To address this question, we evaluated the fidelity of retention of secretory IgM
      and determined the redox status of cysteines in secretory mu proteins in polymers
      and polymer intermediates at various stages of maturation. We demonstrate that
      all secreting B cells and B cell lines secrete assembly intermediates in addition
      to completed, covalent pentameric and hexameric IgM polymers. A fraction of
      assembly intermediates exit the endoplasmic reticulum as individual components,
      mature through the Golgi without undergoing further assembly, and most, if not
      all, are secreted. While the majority of IgM assembly intermediates have exposed
      thiols and are contained within the endoplasmic reticulum where they can be
      utilized for oligomerization, maturing assembly intermediates found in the Golgi
      and extracellular space are completely oxidized. Thus, while the retention of
      unpolymerized IgM is highly efficient, the retention system lacks the ability to
      distinguish fully oxidized assembly intermediates from fully oxidized completed
      polymers. The molecular mechanisms that may contribute to this aspect of IgM
      biogenesis and their implications for the concept of thiolmediated retention are
      discussed.

PMID- 8886988
TI  - An apoptotic endonuclease activated either by decreasing pH or by increasing
      calcium.
AB  - DNA fragmentation in isolated nuclei from the murine IL3-dependent bone marrow
      cell line BAF3 could be stimulated either by decreasing pH below 6.5 or by adding
      microM calcium at neutral pH. An endonuclease which could also be stimulated
      either by a decrease in pH, to 6.5, or by the presence of microM calcium at
      neutral pH, was purified 10(4)-fold from nuclei of BAF3 cells. Digestion of DNA
      with the purified enzyme resulted in 5'-terminal hydroxyl and 3'-terminal
      phosphate ends. These characteristics are distinct from those described for other
      mammalian endonucleases. The possible role of this enzyme in genome digestion
      during apoptosis is discussed.

PMID- 8886989
TI  - Transport of protein kinase C alpha into the nucleus requires intact cytoskeleton
      while the transport of a protein containing a canonical nuclear localization
      signal does not.
AB  - Protein kinase C undergoes a redistribution from the cytosol into the nucleus
      upon various stimuli. Since protein kinase C does not contain any known nuclear
      localization signal, the exact pathway and mechanism of the translocation into
      the nucleus is not known. We used immunofluorescence microscopy to investigate
      the role of the cytoskeleton in this process, and to detect the subcellular
      distribution of protein kinase C alpha in NIH 3T3 fibroblasts. In these cells
      protein kinase C alpha is translocated into the nucleus after stimulation with
      phorbol ester. We observed that cells treated with the cytoskeleton disrupting
      agents cytochalasin B or colchicine do not show the nuclear translocation of
      protein kinase C alpha after stimulation. In contrast, the nuclear accumulation
      of a nuclear localization signal containing reporter protein in an in vitro
      nuclear transport assay is not affected by these drugs. This observation has been
      confirmed for intact cells by microinjection experiments: cells which have been
      incubated with cytochalasin B or colchicine prior to microinjection of the
      reporter protein show the same accumulation in the nucleus as untreated cells.
      Our data show that intact cytoskeleton plays an important role in the
      translocation of protein kinase C alpha into the nucleus but not in the nuclear
      import of a karyophilic reporter protein.

PMID- 8886990
TI  - Regulation of the acquisition of meiotic competence in the mouse: changes in the
      subcellular localization of cdc2, cyclin B1, cdc25C and wee1, and in the
      concentration of these proteins and their transcripts.
AB  - During their development, mammalian oocytes acquire the ability to resume
      meiosis. We demonstrate that the concentration of p34cdc2 increases during the
      acquisition of meiotic competence, as determined by immunoblotting, whereas the
      concentration of cyclin B1 decreases. Laser-scanning confocal microscopy
      corroborated these changes and furthermore indicate that an increase occurs in
      the nuclear concentration of each protein. Results of immunoblotting experiments
      demonstrate that associated with the acquisition of meiotic competence is an
      increase in the concentration of cdc25C, an activator of p34cdc2/cyclin B kinase,
      and a decrease in wee1, an inhibitor of cdc2/cyclin B kinase. These changes were
      again corroborated by laser-scanning confocal microscopy, which also indicates
      that an increase in the nuclear concentration of wee1 occurs. The concentration
      of the transcripts encoding these proteins, however, is essentially similar in
      meiotically incompetent and competent oocytes. Thus, these changes in protein
      concentration that occur during oocyte development likely reflect changes in the
      translational efficiency of their mRNAs. Consistent with this is that the
      relative rate of synthesis of p34cdc2 in meiotically competent oocytes is
      approximately 3 times greater than that in meiotically incompetent oocytes,
      whereas the stability of newly synthesized p34cdc2 is essentially the same in
      each cell type.

PMID- 8886991
TI  - Patch-clamp capacitance analysis of the effects of alpha-SNAP on exocytosis in
      adrenal chromaffin cells.
AB  - We have examined the effect of alpha-SNAP on exocytosis in adrenal chromaffin
      cells by direct assay of exocytosis using patch-clamp capacitance analysis. Cells
      were recorded using the whole cell patch-clamp configuration and the cells
      dialysed with control pipette solution or with a pipette solution containing
      alpha-SNAP or the deletion mutant alpha-SNAP(41-295). The deletion mutant was
      found to be unable to bind to syntaxin allowing a test of the requirement for
      syntaxin-binding for any effect of alpha-SNAP on exocytosis. Following cell
      dialysis for 10 minutes, cells were depolarised five times at 2 minute intervals.
      At each depolarisation step cells dialysed with alpha-SNAP showed a significant
      increase in both the initial rate and extent of exocytosis which was seen as a
      rise in membrane capacitance. This increase in exocytosis was not observed with
      alpha-SNAP(41-295) which instead produced some inhibition of the extent but had
      no effect on the initial rate of exocytosis. These results show directly that
      alpha-SNAP has a specific and marked stimulatory effect on exocytosis in
      chromaffin cells.

PMID- 8886992
TI  - The molecular basis of natural killer (NK) cell recognition and function.
AB  - Natural Killer cells are likely to play an important role in the host defenses
      because they kill virally infected or tumor cells but spare normal self-cells.
      The molecular mechanism that explains why NK cells do not kill indiscriminately
      has recently been elucidated. It is due to several specialized receptors that
      recognize major histocompatibility complex (MHC) class I molecules expressed on
      normal cells. The lack of expression of one or more HLA class I alleles leads to
      NK-mediated target cell lysis. Different types of receptors specific for groups
      of HLA-C, HLA-B, and, very recently, HLA-A alleles have been identified. While in
      most instances, they function as inhibitory receptors, an activatory form of the
      HLA-C-specific receptors has been identified in some donors. Molecular cloning of
      HLA-C-, HLA-B- or HLA-A-specific receptors has revealed new members of the
      immunoglobulin superfamily with two or three Ig-like domains, respectively, in
      their extracellular portion. While the inhibitory form is characterized by a long
      cytoplasmic tail associated with a non-polar transmembrane portion, the
      activatory one has a short tail associated with a Lys-containing transmembrane
      portion. Thus, these human NK receptors are different from the murine Ly49, that
      is a type II transmembrane protein characterized by a C-type lectin domain. A
      subset of activated T lymphocytes expresses NK-type class I-specific receptors.
      These receptors exert an inhibiting activity on T cell receptor-mediated
      functions and may provide an important mechanism of downregulation of T cell
      responses.

PMID- 8886994
TI  - Soluble Fas molecule in the serum of patients with systemic lupus erythematosus.
AB  - The serum level of soluble Fas (sFas) molecules in 35 patients with SLE was
      determined by enzyme-linked immunosorbent assay (ELISA) and its relation to other
      lymphocyte activation markers and clinical parameters was examined. The level of
      sFas increased significantly compared to that in normal subjects, consistent with
      previous reports. There was a significant correlation between the level of sFas
      and that of sCD4, suggesting some relation between sFas and activation of CD4+ T
      cell. Patients with lymphopenia tended to have low levels of sFas, making it
      possible to hypothesize that sFas protects against apoptosis. Although the change
      in the level of sFas protects steroid therapy was variable, some relation to the
      differential activation of T cell subsets was suggested.

PMID- 8886993
TI  - Ataxia-telangiectasia and the ATM gene: linking neurodegeneration,
      immunodeficiency, and cancer to cell cycle checkpoints.
AB  - Defects in regulation of the cellular life cycle may lead to premature cellular
      death or malignant transformation. Most of the proteins known to be involved in
      these processes are mediators of mitogenic signals or components of the cell
      cycle machinery. It has recently become evident, however, that systems
      responsible for ensuring genome stability and integrity are no less important in
      maintaining the normal life cycle of the cell. These systems include DNA repair
      enzymes and a recently emerging group of proteins that alert growth regulating
      mechanisms to the presence of DNA damage. These signals slow down the cell cycle
      while DNA repair ensues. Ataxia telangiectasia (A-T) is a genetic disorder whose
      clinical and cellular phenotype points to a defect in such a signaling system. A
      T is characterized by neurodegeneration, immunodeficiency, radiosensitivity,
      cancer predisposition, and defective cell cycle checkpoints. The responsible
      gene, ATM, was recently cloned and sequenced. ATM encodes a large protein with a
      region highly similar to the catalytic domain of PI 3-kinases. The ATM protein is
      similar to a group of proteins in various organisms which are directly involved
      in the cell cycle response to DNA damage. It is expected to be part of a protein
      complex that responds to a specific type of DNA strand break by conveying a
      regulatory signal to other proteins. Interestingly, the immune and nervous
      systems, which differ markedly in their proliferation rates, are particularly
      sensitive to the absence of ATM function. The identification of the ATM gene
      highlights the growing importance of signal transduction initiated in the nucleus
      rather than in the external environment, for normal cellular growth.

PMID- 8886995
TI  - Viral load, CD4 percentage, and delayed-type hypersensitivity in subjects
      receiving the HIV-1 immunogen and antiviral drug therapy.
AB  - Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1
      Immunogen are reported. In one study, in which 19 subjects received ZDV and 8
      subjects received ddI, treatment with the HIV-1 Immunogen did not affect the
      pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects
      who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0
      years (range, 1.2-5.4 years) received inoculations at 0 and 6 months. At some
      point during this 48-week study, 72% of the subjects (47/65) were receiving
      antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were
      found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV
      1 antigens increased after two inoculations with the HIV-1 Immunogen. In these
      two trials, no serious treatment-related adverse events were documented in the
      subjects. The two studies presented herein are the first to suggest that an
      immune-based therapy such as the HIV-1 Immunogen can be combined safely with
      antiviral drugs, supporting further study to evaluate the clinical utility of
      this approach.

PMID- 8886997
TI  - Serum laminin and basic fibroblast growth factor concentrations in patients with
      complicated Plasmodium falciparum malaria.
AB  - Serum concentrations of laminin and basic fibroblast growth factor (FGF) were
      measured in 20 patients suffering from complicated Plasmodium falciparum malaria
      in Bangkok. Significant higher mean serum concentrations of laminin were
      determined prior to treatment (1973 ng/ml) and 7 days after starting medication
      (1025 ng/ml) in comparison to the control (412 ng/ml). The values remained
      numerically higher for at least 21 days. With regard to serum basic FGF
      concentrations, a peak was found 7 day after starting treatment (35.61 pg/ml). In
      addition, a significant correlation was found for parasite clearance time and
      basic FGF concentration on day 7 (P < 0.01). These increased values of laminin
      and basic FGF may be the consequence of endothelial and basement membrane damage
      induced by sequestration of the parasites. Furthermore, basic FGF might play a
      role in endothelial repair mechanisms after the clearance of the parasites.

PMID- 8886996
TI  - Human cytomegalovirus infection is not increased in common variable
      immunodeficiency.
AB  - It has been postulated that human cytomegalovirus (HCMV) infection may have a
      role in the pathogenesis of common variable immunodeficiency (CVID). Many
      patients have a lymphocyte phenotype similar to that seen in HCMV infection, HCMV
      mononucleosis may precipitate hypogammaglobulinaemia, and a previous small study
      of common variable immunodeficient patients reported a high rate of active HCMV
      infection. This study investigated the presence and activity of HCMV infection in
      102 CVID patients. Buffy coats were examined for the presence of HCMV IE and
      glycoprotein B genes using highly sensitive nested PCR. 30 blood donors of known
      HCMV serologic status were used as controls. There was no significant difference
      in HCMV positivity by PCR between patients and controls. Enrichment for
      mononuclear cells prior to PCR had no effect on sensitivity. Twenty-five patients
      were also examined for HCMV antigenaemia by staining buffy coat cytospins with
      monoclonal antibodies directed against the HCMV pp65 lower matrix protein, a
      technique widely used for diagnosis of active HCMV disease. Only one patient was
      positive (and also positive by PCR). Whilst these results do not exclude prior
      infection contributing to antibody deficiency in a small proportion of CVID
      patients, this study refutes the previously reported increase in active HCMV
      infection in CVID.

PMID- 8886998
TI  - Increased incidence of neutralizing autoantibodies against interleukin-1 alpha
      (IL-1 alpha) in nondestructive chronic polyarthritis.
AB  - Cytokines such as IL-1 and tumor necrosis factor alpha (TNF alpha) play a
      critical role in chronic joint inflammation and destruction. To study their
      regulation, we looked for circulating antiproinflammatory cytokine autoantibodies
      in 318 patients with chronic arthritis by immunoprecipitation with protein G.
      Anti-IL-1 alpha but not anti-IL-1 beta or anti-TNF alpha IgG antibodies were
      detected in 9% of blood donors and 18.9% of chronic arthritis patients. These
      antibodies were found more commonly and at a higher level in patients with
      nondestructive arthritis. Negative correlations were observed between the
      antibody levels and indices of disease activity and joint destruction. There was
      a negative association between the presence of anti-IL-1 alpha antibodies and
      that of HLA-DR4. These circulating anti-IL-1 alpha antibodies were not complexed
      with IL-1 alpha and could block specifically the biological activity of IL-1
      alpha and its binding to membrane IL-1 receptors. These results indicate that
      these antibodies are beneficial, suggesting their contribution in the clinical
      presentation.

PMID- 8887000
TI  - Hormonal modulation of the vaginal bacterial flora in experimental polycystic
      ovarian disease.
AB  - Rats exposed to constant light develop polycystic ovarian (PCO) disease with
      persistent estrus, representing an estrogen-dominant condition. Herein, we report
      that fluctuations seen in the vaginal microflora in cyclic rats were not observed
      in PCO rats with persistent estrus. The vaginal-cervical mucosa of PCO rats
      showed numerous adherent bacteria by scanning electron microscopy, similar to
      that seen in proestrus and estrus rats, but unlike the diestrus rats in which
      fewer organisms adhered to the mucosa. Administration of human chorionic
      gonadotropin induced ovulation in PCO rats, which was associated with a
      significant decrease in serum estradiol, an increase in progesterone, and a
      significant decrease in the estradiol/progesterone ratio compared with baseline
      values (P < 0.01). This also resulted in an influx of leukocytes in the vagina
      with a significant decrease in vaginal anaerobic as well as aerobic bacterial
      flora. These data demonstrate that loss of cyclic ovarian activity in PCO rats
      with persistent estrus causes increased bacterial colonization of the vaginal
      cervical mucosa, and the ovarian hormones appear to modulate the colonization of
      bacteria in the lower genital tract.

PMID- 8886999
TI  - Clinical, hematologic, and immunologic effects of interleukin-10 in humans.
AB  - We conducted a double-blind, placebo-controlled study to investigate the safety,
      pharmacokinetics, and immunological properties of interleukin-10 (IL-10)
      administration in healthy humans. Volunteers received a single intravenous bolus
      injection of recombinant human IL-10 (1, 10, or 25 micrograms/kg) or placebo.
      Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC)
      was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum
      concentrations of IL-10 (15 +/- 1.1, 208 +/- 20.1, and 505 +/- 22.3 ng/ml)
      occurred after 2-5 min for 1, 10, and 25 micrograms/kg IL-10, respectively. The
      terminal-phase half-life was 3.18 hr. A transient leukocytosis (24-63% above
      baseline) was observed 6 hr after injection, which coincided with a dose
      dependent decrease (12-24%) in neutrophil superoxide generation. There was a
      marked inhibition (60-95%) of endotoxin-induced IL-6 production from whole blood
      in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood
      was reduced in the 10 micrograms/kg group. In PBMC stimulated with
      phytohemagglutinin and phorbol ester, there was a decrease (72-87%) in interferon
      gamma (IFN gamma) production 6 hr after IL-10 with a return to pre-IL-10 levels
      after 24 hr. This reduction was only partially associated with a decrease in the
      number of CD2-bearing cells. We conclude that IL-10 administration into humans is
      without significant side effects, and a single injection reduces ex vivo
      production of IL-6, IL-8, and IFN gamma.

PMID- 8887001
TI  - Optimal conditions for collection of blood samples for assay of alpha 2
      macroglobulin-trypsin complex-like substance (MTLS).
AB  - We have developed an enzyme-linked immunosorbent assay (ELISA) for the specific
      quantification of alpha 2-macroglobulin-trypsin complex-like substance (MTLS). To
      exclude artifacts in measured values of MTLS, the conditions for collection of
      blood samples are critical. In the present study, we have determined the optimal
      conditions for blood collection and investigated the role of MTLS as a clinical
      tool for diagnosis in pancreatitis. Results obtained are as follows: (1) MTLS
      levels of all sera were more than 10-fold higher than the corresponding plasma;
      (2) MTLS levels of heparinized plasma were the lowest among plasma with three
      anticoagulants (sodium citrate, sodium EDTA and heparin); (3) some kinds of blood
      collection tubes containing heparin were not suitable for the sampling; (4) MTLS
      values of plasma obtained by blood collection tubes containing Trasylol and
      sodium EDTA were demonstrated more stable and lower than those obtained by
      heparin tubes; and (5) under these conditions, we can exclude elevation of MTLS
      values caused by inappropriate blood sampling and find the time course of the
      elevation reflecting clinical course of a patient with acute pancreatitis and a
      patient after endoscopic retrograde cholangiopancreatography (ERCP). The optimal
      conditions for collection of blood samples were as follows. Blood sampling should
      be performed by blood collection tubes containing Trasylol (50 microliters/ml
      blood) and sodium EDTA (1.5 mg/ml blood). The samples were immediately stored at
      4 degrees C and centrifuged at 3,000 rpm for 15 min. The plasma were stored in
      plastic tubes at 4 degrees C until assayed.

PMID- 8887002
TI  - Alteration of the aPA ELISA by UV exposure of polystyrene microtiter plates.
AB  - Interlaboratory inconsistencies in antiphospholipid antibody (aPA) solid phase
      assays have prompted controversy in clinical laboratory testing for aPA. We found
      that the aPA ELISA can be influenced by the type of microtiter plate utilized and
      by the conditions in which the plates are stored. By exposing 96-well, flat
      bottom polystyrene microtiter plates to short wave UV light (254 nm), the aPA
      ELISA signal decreased in a UV dose-dependent manner. No effect was seen with
      long wave UV light (366 nm). These results were independent of the antibody
      isotype under study or the phospholipid (PL) antigen used: anionic
      phosphatidylserine (PS) and cardiolipin (CL), or zwitterionic
      phosphatidylethanolamine (PE). Purified human beta 2-glycoprotein I (beta 2 GPI),
      a known cofactor for anionic PL, and rabbit anti-beta 2 GPI antisera were used to
      demonstrate that beta 2 GPI bound equally to UV treated and untreated microtiter
      plates. In contrast, recognition of beta 2 GPI on an anionic PL surface was
      decreased on UV treated plates, suggesting that UV exposure alters the lipid
      binding properties of the microliter plate. To determine whether UV exposure
      inhibited PL binding directly or caused a change in the way the PL was bound, the
      amount of PL bound to UV treated and untreated plates was measured by using
      fluorescent labeled PS and a fluorimeter. PS binding was decreased by 53% in UV
      treated wells as compared to untreated wells. These data show that short wave UV
      exposure reduces PL binding to polystyrene microtiter plates, thereby reducing
      the amount of beta 2 GPI bound to PL coated ELISA plates. Thus by using UV
      exposed microtiter plates, decreased or false-negative a PA ELISA results may be
      obtained for aPA positive plasmas.

PMID- 8887003
TI  - Evaluation of recent techniques for detection of red blood cell antibodies in
      sera of reference samples, patients, pregnant women, and blood donors.
AB  - The sensitivity of the low ionic strength solution antiglobulin test (LISS-AGT),
      polyethylene glycol antiglobulin test (PEG-AGT), low ionic strength solution
      solid-phase antiglobulin test (LISS-SPAT), gel low ionic strength solution
      antiglobulin test (GEL-LISS), and gel papain test (GEL-PAP) was compared in
      titration studies of 460 sera containing identified IgG alloantibodies. The GEL
      PAP was 100% sensitive to detect Rh antibodies, whereas the PEG-AGT was the most
      sensitive to detect Kell, Duffy, Kidd, Ss, and rare blood group antibodies. The
      better performance of PEG-AGT was especially obvious with Kell, Duffy, and Ss
      antibodies (S = 100%). When the sensitivity of the LISS-AGT, PEG-AGT, GEL-LISS,
      and GEL-PAP was evaluated in different routines, the GEL-LISS showed to be more
      sensitive than PEG-AGT in the detection of clinically significant antibodies.
      These discrepant results showed that the performance of a technique may change
      when it is applied as a routine.

PMID- 8887004
TI  - Sensitive enzyme-linked immunosorbent assay for adult T-cell leukemia-derived
      factor and normal value measurement.
AB  - Four different monoclonal antibodies against recombinant adult T-cell leukemia
      derived factor (ADF), identical to thioredoxin, were established and used for the
      determination of ADF concentration in serum. Using two of the monoclonal
      antibodies, we developed a two-step enzyme-linked immunosorbent assay (ELISA) for
      ADF. This ELISA showed a highly specific reactivity on ADF with no cross
      reactivity to several proteins with homologue sequence on the active center. The
      detection limit of the assay was 2.0 ng/ml (mean +/- 2 SD). The intra- and
      interassay coefficients of variation (CV) were 0.81-3.74% (n = 8) and 4.78-6.97%
      (n = 7), respectively. The normal value of ADF mean concentration from 145
      healthy donors was 40.8 ng/ml.

PMID- 8887005
TI  - Validation of a quantitative RNA PCR assay for HIV-1 in human plasma.
AB  - A quantitative human immunodeficiency virus type 1 (HIV-1) RNA polymerase chain
      reaction assay has been validated analytically and clinically in > 13,000
      samples. The assay is highly reproducible with intra- and inter-assay precision
      of 16% and 19%, respectively. In 1,542 of 1,548 subjects with CD4+ counts of 0
      500 cells per mm3, viral RNA levels were quantifiable and ranged from
      approximately 3,000-52,200,000 copies per milliliter. Median plasma HIV-1 RNA
      values were inversely proportional to CD4+ counts from 0-400 cells per mm3. When
      patients were off antiretroviral therapies for approximately 14 days prior to the
      initial baseline RNA PCR evaluation, the mean variance between the two baseline
      values was 23% (0.1 log). Of these patients, 95% had a sufficient plasma viral
      load to quantitate a 10-fold (1 log) diminution in viral load caused by antiviral
      therapy. In contrast, only 20% and 45% of these subjects had sufficient p24 and
      ICD p24 levels to detect a 50% diminution in circulating virus. The high
      precision and reproducibility of this quantitative RNA PCR assay provide an
      enhanced means of evaluating therapeutic drug regimens for HIV-1.

PMID- 8887006
TI  - Evaluation of a new automated third-generation anti-HCV enzyme immunoassay.
AB  - The new Cobas Core Anti-HCV EIA was evaluated in two centers for its ability to
      detect antibodies directed to hepatitis C virus in human serum. This assay, which
      can be run fully automated on a random access analyzer, was compared with three
      other commercially available screening tests: the Ortho HCV 3.0 ELISA, the Murex
      anti-HCV, and the Abbott HCV EIA second generation. Positive or discrepant
      results were further investigated using the Wellcozyme HCV Western Blot or the
      Abbott Matrix HCV assays. The results obtained from analyzing 5045 serum samples
      showed a high correlation between the Cobas Core Anti-HCV EIA and the other
      screening assays, ranging from 98.9% to 99.9%. Diagnostic specificities and
      sensitivities ranged from 99.7% to 100% and from 98.8% to 100%, respectively. In
      this study, the Cobas Core Anti-HCV EIA proved to be a very convenient test, able
      to perform at the highest levels of sensitivity and specificity.

PMID- 8887007
TI  - Technical report: Part 1. Basic requirements for designing optimal
      oligonucleotide probe sequences.
AB  - Although oligonucleotides can be easily synthesized and used in a variety of
      scientific fields, a major problem exists for each application: the difficulty of
      obtaining optimal oligonucleotide sequences. Oligonucleotide sequences have been
      described in each publication; however, little is disclosed on how to design such
      sequences and how specific each sequence is. This report introduces a new concept
      of computer hybridization simulation based on "thermodynamic hybridizability",
      which can overcome the problems of conventional homology analyses. Then, all the
      necessary components and factors for designing optimal probe sequences, such as
      hybridization strength, specificity, secondary structure, length of probes, probe
      to-probe interaction, are discussed in detail. Also included are procedures for
      manipulating various types of data for selection of optimal oligonucleotides.
      This report provides a general guideline for optimal probe design and encourages
      basic and clinical scientists to enhance their research activities by using
      optimal oligonucleotides.

PMID- 8887008
TI  - Technical report: Part 2. Basic requirements for designing optimal PCR primers.
AB  - Designing optimal polymerase chain reaction (PCR) primer sequences is one of the
      critical factors for successful PCR with sensitive, specific, and assay-to-assay
      reproducible results. In this review, all the requirements of PCR primer
      sequences are summarized, such as location, size of amplicon, length of primers,
      nucleotide composition, Tm, 3' terminal hybridization strength and frequency,
      hairpin formation energy, primer-to-primer interaction, specificity, and location
      of mismatches to sequences of cross-hybridization. The report also discusses how
      to explore these various types of information for more advanced PCR applications,
      which include nested PCR, multiplex PCR, competitive PCR, long PCR, point
      mutation detection, degenerate primers, and PCR cloning.

PMID- 8887009
TI  - Simple and more sensitive immune complex transfer enzyme immunoassay for antibody
      IgG to reverse transcriptase of HIV-1 using microplates, modified polystyrene
      solid phase and fluororeader.
AB  - In a previously reported ultrasensitive enzyme immunoassay (immune complex
      transfer enzyme immunoassay) for antibody IgG to HIV-1, polystyrene beads in test
      tubes were handled with tweezers, and bound beta-D-galactosidase activity was
      measured with a fluorometer. The use of tweezers was causative of false
      positivity by carryover, and testing many samples was difficult. Recently, these
      drawbacks have been minimized using microplates, a fluororeader, and modified
      polystyrene beads with sticks for easy handling. The modified polystyrene beads
      were transferred from wells to wells more quickly and easily without tweezers,
      eliminating false-positivity due to carryover. The fluorescence intensity for
      bound beta-D-galactosidase activity was quickly measured with a fluororeader. As
      a result, it became easy to test many samples with high reliability. However,
      modified polystyrene beads used were handmade, and the sensitivity was lower than
      the previous assay with test tubes. In the present study, the condition of the
      immune complex transfer enzyme immunoassay for antibody IgG to reverse
      transcriptase of HIV-1 was optimized using microplates, a fluororeader, and
      polystyrene solid phase with stick, which is commercially available. Testing many
      samples became easy with higher sensitivity.

PMID- 8887010
TI  - Ultrasensitive and more specific enzyme immunoassay (immune complex transfer
      enzyme immunoassay) for p24 antigen of HIV-1 in serum using affinity-purified
      rabbit anti-p24 Fab' and monoclonal mouse anti-p24 Fab'.
AB  - Previously, an ultrasensitive enzyme immunoassay (immune complex transfer enzyme
      immunoassay) for p24 antigen of HIV-1 was developed. The immune complex
      comprising 2,4-dinitrophenyl-biotinyl-bovine serum albumin-rabbit anti-p24 Fab'
      conjugate, p24 antigen, and rabbit anti-p24 Fab' -beta-D-galactosidase conjugate
      was trapped onto polystyrene beads coated with affinity-purified (anti-2,4
      dinitrophenyl group) IgG, was eluted with epsilon N-2, 4-dintrophenyl-L-lysine,
      and was transferred to polystyrene beads coated with streptavidin. beta-D
      Galactosidase activity bound to the streptavidin-coated polystyrene beads was
      assayed by fluorometry. This assay was highly sensitive. However, bound beta-D
      galactosidase activity had to be assayed for a long time (20 h), and the
      nonspecific signal was observed in 5% serum samples from subjects with low risk
      of HIV infection. In the present study, the assay time for bound beta-D
      galactosidase activity was shortened to 2.5 h by using 2,4-dinitrophenyl-biotinyl
      bovine serum albumin-affinity-purified rabbit anti-p24 Fab' conjugate and
      affinity-purified rabbit anti-p24 Fab' -beta-D-galactosidase conjugate.
      Furthermore, the nonspecific signal was found to increase with increasing periods
      of time for storage of serum samples at -20 degrees C, and this increase was
      prevented without prolongation of the assay time for bound beta-D-galactosidase
      activity and without loss of the sensitivity by substituting monoclonal mouse
      anti-p24 Fab'-beta-D-galactosidase conjugate for affinity-purified rabbit anti
      p24 Fab'beta-D-galactosidase conjugate.

PMID- 8887011
TI  - Insulin resistance and diabetes mellitus.

PMID- 8887012
TI  - Research prospects with benfluorex.
AB  - The recent recognition that insulin resistance is associated with a number of
      risk factors for atherosclerotic cardiovascular disease has increased the
      interest in agents that are able to improve insulin sensitivity. The capacity of
      benfluorex (Mediator) to enhance insulin action has led to much speculation
      regarding its mechanism of action. Chronic benfluorex treatment, in a variety of
      genetic and dietary animal models of diabetes and insulin resistance, has been
      shown to diminish, circulating insulin levels and to decrease blood glucose,
      triglycerides, and cholesterol concentrations. From these studies, it is possible
      to postulate a multifactorial mode of action of this drug that involves three
      independent but interactive processes: (1) a direct effect on insulin target
      tissues, mediated by mechanisms distal to the binding of insulin to its receptor,
      (2) modulation of the glucoregulatory hormone balance, including a diminution in
      both adrenal and sympathetic tone, leading to improved hepatic sensitivity to
      insulin, and (3) reduced hepatic and muscle lipid availability, leading to
      improved glucose utilization in skeletal muscle. The multiplicity of the
      neuroendocrine and biochemical effects of benfluorex cannot be explained by a
      single cellular or molecular action. It has been suggested that insulin
      sensitizers may act on key molecules involved in the sequence of biochemical
      events involving the insulin signal transduction process. The identification of
      these molecular targets and the determination of their relative importance in the
      treatment of type II diabetes remains to be established and constitutes the main
      subject of ongoing research with benfluorex.

PMID- 8887013
TI  - Therapeutic problems in type II diabetic patients developing insulin requirement.

PMID- 8887014
TI  - Therapeutic effect of benfluorex in type II diabetic patients on diet regimen
      alone.
AB  - A randomized double-blind study of benfluorex (150 mg x 3 daily) versus placebo
      was conducted over 3 months in 32 type II diabetic patients (24 men and 8 women,
      aged 52 +/- 8.4 years) with mild stable obesity [body-mass index (BMI) 27 +/- 1.6
      kg/ m2], moderate fasting hyperglycemia (fasting blood glucose 9 +/- 0.5 mmol/L,
      HbA1c 6.7 +/- 0.9%) and moderate hyperinsulinemia (18.6 +/- 3.0 microU/mL) when
      on treatment with diet alone. After a 1-month placebo run-in period, subjects
      were randomized to benfluorex or placebo three tablets daily. Inclusion
      parameters and end-of-study measures were body weight, BMI, fasting blood
      glucose, glycemic profile, HbA1c, fasting insulinemia, basal and stimulated C
      peptide, and an insulin tolerance test (0.1 U/kg). The groups were homogeneous at
      baseline, except for glycemic profile (higher postprandial glycemia in the group
      randomized to benfluorex). At the end of the study, the groups did not differ in
      body weight or BMI; however, HbA1c decreased more with benfluorex (6.0 +/- 1.0%
      versus 6.8 +/- 0.9%, p = 0.024), as did the mean glycemic profile (7.8 +/- 1.4
      versus 8.5 +/- 1.7 mmol/L, p < 0.001), including a particular decrease in
      postprandial glycemia. The decreases in fasting blood glucose and insulinemia
      appeared larger with benfluorex (7.7 +/- 1.3 versus 8.4 +/- 1.6 mmol/L and 13.5
      +/- 4.5 versus 16.1 +/- 5.1 microU/mL, respectively), but were not statistically
      significant. The increase in the insulin sensitivity index (Kitt) was greater
      with benfluorex (+0.54 +/- 1.4 versus +0.25 +/- 1.3%/mn), but the difference was
      not statistically significant. The same was observed for the stimulated C
      peptide. In type II diabetics with mild obesity and hyperglycemia previously
      managed with diet alone, benfluorex has significant long-term effect on HbA1c and
      mean daily blood glucose, and tends to lower insulinemia.

PMID- 8887015
TI  - Therapeutic benefit of benfluorex in type II diabetic patients treated with
      sulfonylureas.
AB  - The objective of this study was to evaluate the effect of benfluorex in type II
      diabetic patients already treated with sulfonylureas (SU) in a randomized placebo
      controlled trial. After a 4-week placebo run-in, 68 patients (49 men and 19
      women; age range 40-70 years; known duration of diabetes 0.5-19 years) were
      randomized to double-blind 12-week treatment with benfluorex (B) or placebo (P).
      Primary end points were HbA1c and fasting blood glucose (FBG). Secondary end
      points were glucose tolerance (meal test over 120 min), plasma insulin, C
      peptide, and lipid profile. Results were analyzed using both intention-to-treat
      analysis (ITT) in patients completing at least one treatment visit and per
      protocol analysis in those completing the whole study. There were no baseline
      differences between the two groups in any study parameter. Fifty-eight patients
      completed the study (28 B, 30 P), and 66 patients (33 B, 33 P) were eligible for
      ITT analysis. Over the 12-week treatment period, FBG decreased by 14.9% in the B
      group (-1.39 mmol/L, p < 0.001), and 3.2% in the P group (-0.28 mmol/L, NS)
      according to the ITT analysis and by 17.4% (p < 0.001) and 3.8% (NS),
      respectively, in the per protocol analysis. The difference in FBG outcome between
      the two groups was significant (p = 0.009 and p = 0.004, respectively). In
      patients completing the study, mean HbA1c decreased in the B group (-0.66%, p =
      0.005) and remained stable in the P group (+0.14%, NS). HbA1c outcome differed
      between the two groups (p = 0.007). The decrease in AUCglucose was greater in the
      B group than in the P group (-210 +/- 220 versus -60 +/- 270 mmol/L x 120 min, p
      = 0.026). Plasma insulin and C-peptide changes did not differ between the two
      groups. Low-density lipoprotein (LDL) cholesterol decreased in B patients and was
      stable in P patients (-0.43 versus -0.05 mmol/L, p = 0.026). Of the 68 randomized
      patients, six on B and four on P reported at least one adverse event, causing
      dropout in five and two patients, respectively. In conclusion, benfluorex is an
      effective agent for combination therapy in type II diabetic patients poorly
      controlled on SUs alone.

PMID- 8887016
TI  - Effects of posture on the plasma hormonal and renal water-electrolyte excretory
      responses to acute water loading in diabetic subjects with hypoadrenergic
      orthostatic hypotension.
AB  - The effects of posture on the plasma hormonal and renal water-electrolyte
      excretory responses to acute water loading (20 mL/kg BW, orally) were studied in
      six non-insulin-dependent diabetes mellitus (NIDDM) subjects with hypoadrenergic
      orthostatic hypotension (HOH), eight NIDDM subjects without HOH, and seven
      nondiabetic subjects. The three groups were similar with respect to basal levels
      of mean blood pressure (MBP), serum sodium and osmolality, plasma renin activity
      (PRA), the plasma volume regulatory hormones alpha-atrial natriuretic peptide
      (ANP), arginine vasopressin (AVP) and aldosterone, and urinary water and sodium
      excretion. In the supine state, while allowing the subjects to stand only to
      void, water loading resulted in no changes in MBP and similar responses of these
      plasma and urinary parameters in the three groups. In the standing state, water
      loading produced responses of MBP, and plasma and urinary parameters comparable
      to those in the supine state in the diabetic group without HOH and the
      nondiabetic group. In the diabetic group with HOH, however, MBP and hourly
      urinary water and sodium excretion rates were low compared to those in the other
      two groups. During water loading, plasma ANP decreased, and, despite the fall of
      MBP, plasma AVP remained unchanged, and PRA and plasma aldosterone increased
      normally in the diabetic group with HOH. These results demonstrate that, in NIDDM
      subjects with HOH, changing from lying to standing induces deranged renal water
      and sodium handling after water loading, accompained by a decrease in plasma ANP,
      and inadequate responses of plasma AVP, PRA, and plasma aldosterone to
      hypotension.

PMID- 8887017
TI  - Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and
      serum lipids in patients with type II diabetes mellitus.
AB  - The present study was undertaken to investigate the efficacy of a new, highly
      purified (purity greater than 91%), ethyl esterification product from natural
      eicosapentaenoic acid (EPA-E, C20:5 omega 3) in patients with type II diabetes
      mellitus (NIDDM). Hemodynamic changes were assessed at the level of the dorsalis
      pedis artery using an ultrasonic color Doppler duplex system before and after
      oral administration of EPA-E at a dose of 1800 mg/day for 48 weeks. The cross
      sectional area of the dorsalis pedis artery increased significantly from 2.5 +/-
      0.2 to 3.9 +/- 0.4 mm2 (48 weeks, mean +/- SE, p < 0.05). Moreover, EPA-E
      improved the clinical symptom (coldness, numbness) as well as the vibration
      perception threshold sense of the lower extremities [from 32.1 +/- 8.5 to 16.1 +/
      4.8 (48 weeks) microns]. A significant decrease of serum triglycerides was also
      noted by EPA-E administration. Furthermore, significant decrease of the excretion
      of albumin in urine [from 24.4 +/- 3.3 to 13.9 +/- 1.8 (48 weeks) mg/g.Cr, p <
      0.05]. The results of this study suggest that EPA-E has significant beneficial
      effects on diabetic neuropathy and serum lipids as well as other diabetic
      complications such as nephropathy and macroangiopathy.

PMID- 8887018
TI  - Duration-dependent changes in calcium responsiveness in the alloxan-diabetic rat
      intestine.
AB  - Disturbances of the gastrointestinal tract that are common in diabetes mellitus
      seem to be related to intestinal motility. In experimental models of diabetes,
      decreased calcium sensitivity has been demonstrated in various smooth muscles
      including those in the gastrointestinal tract. The main purpose of the present
      study was to examine further the calcium sensitivity in diabetic rat intestine
      and to understand if changes in the calcium sensitivity occur at an earlier stage
      of the disease. For this purpose, the effects of potassium and calcium were
      evaluated on nondepolarized and depolarized duodenum from rats with alloxan
      diabetes for 1 and 8 weeks and their age-matched controls. To evaluate the
      calcium sensitivity in rat duodenum, apparent affinity constants (pD2 values) and
      intrinsic activities (alpha E values) were calculated for every experimental
      conditions examined in this study. Both values (pD2 and alpha E) for the effects
      of potassium and calcium on the nondepolarized and depolarized duodenum,
      respectively, were not changed in 1-week diabetic rats. In contrast, intrinsic
      activities for the effects of potassium and calcium were found to be
      significantly decreased (p < 0.001) in the nondepolarized and depolarized
      duodenum from rats with alloxan diabetes for 8 weeks, whereas apparent affinity
      constants were not altered in this case. Taking into consideration all these
      experimental findings, the decreased calcium sensitivity in gastrointestinal
      tract seems to be closely related to decreased calmodulin levels and may occur at
      a later stage of diabetes as a linkage to long-term gastrointestinal
      complications.

PMID- 8887019
TI  - Short- and long-range complications in offspring of diabetic mothers.
AB  - The perinatal mortality rate of infants of diabetic mothers (IDMs) has declined
      dramatically from 250 per 1000 live births in the 1960s to a near-normal 20 per
      1000 live births in the 1980s. Five to 8% of all IDMs suffer from major
      congenital malformations, and it is the latter that are responsible for 50% of
      these perinatal deaths. It has been shown that tight glycemic control prior to
      conception and during pregnancy can prevent an excess rate of congenital
      malformations, fetal macrosomia, birth trauma, and neonatal respiratory distress
      syndrome. We briefly review the short- and long-range complications that occur in
      offspring of diabetic mothers (ODMs) from gestation through young adulthood.
      Short-term neonatal complications, such as hypoglycemia, hypocalcemia,
      hypomagnesemia, hyperbilirubinemia, and polycythemia, are related mainly to fetal
      hyperinsulinemia, hypoxemia, and prematurity. They are readily controllable
      within the setup of modern neonatal intensive care units. Long-range
      complications include an increased rate of childhood and adolescent obesity,
      impaired glucose tolerance or diabetes mellitus, and subtle neuropsychological
      dysfunctions. These may be related to the severity of the maternal hyperglycemia
      during pregnancy, the consequent fetal hyperinsulinemia, and third trimester
      maternal lipid metabolism disturbances. Today we have at hand the knowledge and
      tools to properly treat both pregestational and gestational diabetes. Increased
      education of the general practitioner and the target population regarding early
      referral of pregestational diabetic mothers and the implementation of screening
      programs for gestational diabetes will further reduce diabetic pregnancy-related
      morbidity.

PMID- 8887020
TI  - Medical ethnobotany survey in Martinique.
AB  - From September 1990 to December 1994, the authors conducted an ethnobotanical
      survey within the population of Martinique. Two hundred and sixty-one plants used
      for medicinal purposes were gathered. It was possible to identify 251 species
      (96%). Traditional medicinal practices, although threatened by the modern
      pharmacopoeia, remain alive, especially among the elderly population.

PMID- 8887021
TI  - Antimicrobial evaluation of some plants used in Mexican traditional medicine for
      the treatment of infectious diseases.
AB  - Twelve methanolic plant extracts from botanical species used in traditional
      medicine in Morelos, Mexico to cure infectious diseases have been subjected to a
      screening study to detect potential antimicrobial activity against Staphylococcus
      aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The
      antimicrobial activity of the products was evaluated using colonies growing in
      solid medium, establishing the minimal concentration required to inhibit their in
      vitro growth (MIC). The results showed that extracts from Eucalyptus globolus
      Labill, Punica granatum L., Artemisia mexicana Wild., and Bocconia arborea Watt.
      possess strong in vitro antimicrobial activity against the tested microorganisms.

PMID- 8887022
TI  - An ethnobotanical study of the traditional medicine of the Mestizo people of Suni
      Mirano, Loreto, Peru.
AB  - Research on the ethnobotany of Mestizos in Suni Mirano in 1994 documented 60
      plant species used for medicinal purposes. Some cultural data on traditional
      healing and etiology were also collected. Of these 60 species, 31 were submitted
      to antibacterial and antifungal assays in the presence and absence of UV light
      and a number of species were shown to be active.

PMID- 8887023
TI  - Evaluation of the calcium-antagonist, antidiarrhoeic and central nervous system
      activities of Baccharis serraefolia.
AB  - Baccharis serraefolia is a widely used plant to treat diarrhoea in Mexican
      traditional medicine. Although the methanolic extract of this plant has shown an
      important dose-dependent spasmolytic activity, its underlying mechanism has not
      been studied. In the present work, the methanolic extract of B. serraefolia
      significantly delayed the onset of tonic seizures induced by strychnine and
      pentylenetetrazol; besides, it diminished the death rate and number of animals
      that exhibited convulsions. It produced potentiation of the hypnotic effect of
      pentobarbital. Oral administration produced an inhibition of gastrointestinal
      transit in mice as effective as that produced by loperamide. As to the effect on
      smooth muscles, the active extract produced an inhibition of contraction induced
      electrically, which could not be reversed by naloxone. The calcium concentration
      contraction curve showed a rightward displacement when the extract was added to
      isolated guinea pig ileum depolarized with high K+ and cumulative concentrations
      of Ca2+. The results suggest that the methanolic extract does not interact with
      classical opiate receptors and its effects, at least that produced on smooth
      muscle, may be due to a probable interference with calcium influx and/or calcium
      release from an intra-cellular store.

PMID- 8887024
TI  - Antitumour-promoting and antitumour activities of the crude extract from the
      leaves of Juniperus chinensis.

PMID- 8887025
TI  - Fungicide and fungiostatic effects of xanthoxyline.

PMID- 8887026
TI  - Preliminary studies of analgesic and anti-inflammatory properties of Caesalpinia
      ferrea crude extract.
AB  - The crude aqueous extract of the fruits of Caesalpinia ferrea Mart. (Leguminosae)
      has been investigated for possible anti-inflammatory and analgesic properties.
      The carrageenan induced rat hind paw edema was significantly inhibited (P < 0.05)
      by oral administration of 300 mg/kg of this extract. A centrally mediated
      analgesic effect was not observed, however, there was a dose dependent reduction
      in the number of total writhes induced by acetic acid.

PMID- 8887027
TI  - Regulation of complement C3 synthesis by interleukin-1 and transforming growth
      factor-beta in rat non-transformed intestinal epithelial cell line, IEC-6.
AB  - Intestinal epithelial cells are an important source of many biologically active
      molecules that modulate immune responses in the mucosa. The purpose of this study
      was to demonstrate the synthesis of complement C3 component in the rat non
      transformed crypt-like intestinal epithelial cell line, IEC-6. Unstimulated IEC-6
      cells secreted a low level of C3 protein and showed weak expression of C3 mRNA.
      The addition of interleukin (IL)-1 beta induced a dose- and time-dependent
      increase in C3 production. These effects of IL-1 beta were observed at a
      concentration as low as 0.01 ng/ml and reached a plateau at a concentration of 5
      ng/ml. The effects were observed at the mRNA level as early as 6 h after the
      beginning of incubation. Transforming growth factor (TGF)-beta alone had no
      effect. However, TGF-beta at low concentrations (0.001-1 ng/ml) enhanced the
      effect of IL-1 beta in increasing C3 production; this enhancement was not
      observed at high concentrations (5-10 ng/ml). These effects of TGF-beta were also
      observed at the mRNA level. The present findings indicate that intestinal
      epithelial cells are indeed capable of synthesizing complement C3 in response to
      IL-1 beta and TGF-beta.

PMID- 8887028
TI  - Tissue superoxide dismutase (SOD) activity and immunohistochemical staining in
      acute appendicitis: correlation with degree of inflammation.
AB  - The mechanism of progression of appendicitis has not been clarified. We examined
      tissue superoxide dismutase (SOD) activity, thiobarbituric acid reactive
      substance (TBARS), and the localization of Cu, Zn-SOD in 56 inflamed appendices
      in relation to histopathological classification. There was a significant
      difference in SOD activity between catarrhal appendix and phlegmonous and
      gangrenous appendix (2.3 +/- 0.1 vs 5.0 +/- 0.2 and 4.6 +/- 0.6 units/mg protein,
      respectively P < 0.05). TBARS value was highest in gangrenous appendix, being
      significantly different from the levels in the other two types (0.47 +/- 0.04 vs
      0.19 +/- 0.01 n mol/mg protein, in catarrhal and 0.20 +/- 0.02, in phlegmonous
      appendix P < 0.05). Positive staining for Cu, Zn-SOD was demonstrated in 64% of
      catarrhal appendices, 96% of phlegmonous appendices, and 75% of gangrenous
      appendices, and intense positive staining was recognized in 9%, 28%, and 40% of
      these appendices, respectively. These results indicated that active oxygen
      influences the degree of inflammation in phlegmonous and gangrenous appendicitis.
      Gangrenous appendicitis and the other two types of appendicitis seemed to be
      different entities.

PMID- 8887029
TI  - Relationship between morphological diversity and AgNORs or cathepsin B expression
      in colorectal cancers.
AB  - The biological characteristics associated with the morphological diversity of
      colorectal cancers were investigated to elucidate the causes of this diversity.
      We examined the proliferative and infiltrating activity of tumor cells, indicated
      by the mean number of Ag nucleolar organizer region associated proteins (NORs)
      per nucleus (MNA) and the immunohistochemical response to cathepsin B(CB), in
      various morphological types of early and advanced colorectal cancers. We examined
      73 colorectal cancers obtained by endoscopic and surgical resection. MNA values
      for sessile and flat-elevated cancers were greater than the values for
      pedunculate, subpedunculate, and flat-or-depressed early cancers (sessile, P <
      0.05). In advanced cancers invading the muscularis propria, protruding cancers
      showed significantly higher MNA values than small ulcerative cancers (P < 0.01).
      CB expression increased significantly with the progression of colorectal cancers
      (P < 0.01), but was not related to morphological diversity in early and advanced
      cancers. In both sessile and flat cancers, CB expression was higher in moderately
      differentiated than in well differentiated adenocarcinomas. These results
      indicate that, in colorectal cancers, protruding early cancers without stalks and
      protruding advanced cancers have higher proliferative activity than pedunculate
      or flat early cancers and small ulcerative advanced cancers, respectively, and
      that CB expression is not associated with morphological diversity, but with depth
      of invasion and histological differentiation.

PMID- 8887030
TI  - Breath hydrogen and methane excretion produced by commercial beverages containing
      dietary fiber.
AB  - Soft drinks containing dietary fiber are popular in Japan. There seem to be two
      types, one containing polydextrose and the other, oligosaccharide. These
      beverages are claimed to be useful for constipation or obesity, but data are
      scanty. We examined four such fiber-containing beverages [Fibe-mini Otsuka
      Pharmaceuticals (Tokyo, Japan), Seni and Oligo Takeda Food Engineering (Osaka,
      Japan), Oligo CC (Calpis Food Engineering, Tokyo, Japan), and Sapitus 5289
      Nakakita Pharmaceuticals (Nagoga, Japan)] for large intestine fermentability by
      measuring breath hydrogen (H2) and methane (CH4). Five healthy subjects (two men,
      three women, 22-48 years old) participated in the study. Breath H2 and CH4 were
      measured with a MicroLyzer (Quintron Instruments, Milwaukee, Wis.). Breath H2
      increased within 2h of beverage consumption, but CH4 excretion was observed in
      only two subjects. Orocecal transit time was constant for all beverages. Total H2
      plus CH4 excretion (AUC; area under the curve) after lactulose was 1294 +/- 250
      ppm x min/g fiber. AUC for Oligo CC was significantly greater than that for Fibe
      mini or Sapitus 5289 (P < 0.05). The AUCs of Fibe-mini, Seni and Oligo, Oligo CC,
      and Sapitus 5289 were 41%, 129%, 174%, and 40%, respectively, that of lactulose.
      It is concluded that commercial fiber-containing drinks produce H2, and CH4 in
      some people. Oligosaccharide produces more H2 and CH4 than polydextrose.

PMID- 8887031
TI  - Amebic liver abscess.
AB  - We report eight cases of amebic liver abscess. All patients were men, and four
      were homosexual. Five of the eight patients had syphilis, but the four homosexual
      patients who were tested for HIV infection were negative. Ultrasonography (US),
      with or without needle aspiration, is the best method for diagnosing amebic liver
      abscess, and the treatment of choice is US-guided needle aspiration of the
      abscess followed by metronidazole therapy. Complication by other sexually
      transmitted diseases is another important factor affecting the treatment of this
      disease.

PMID- 8887032
TI  - Prevalence of hepatitis C virus infection among female prostitutes in Fukuoka,
      Japan.
AB  - To assess the risk of sexual transmission of hepatitis C virus (HCV), we surveyed
      female prostitutes to determine the prevalence of antibody to HCV (anti-HCV) and
      HCV RNA. Anti-HCV was examined with a second generation anti-HCV test employing a
      passive hemagglutination assay. HCV RNA was detected by two-stage polymerase
      chain reaction with primers deduced from the 5'-noncoding region of the HCV
      genome. All studies were performed in Fukuoka, Japan, from 1989 through 1992 and
      all subjects were Japanese and had no history of intravenous drug abuse. The
      prevalence of anti-HCV was significantly higher in the prostitutes (10.1%;
      61/604) than in the controls (female blood donors; 0.8%; 52/6632) (P < 0.001).
      HCV RNA was found in 73.2% of the anti-HCV-positive prostitutes. The prevalence
      of anti-HCV among prostitutes increased with the number of years spent in
      prostitution (P < 0.05). Prostitutes with a history of syphilis had a higher
      prevalence of anti-HCV than those with no history of syphilis, irrespective of
      the number of years in prostitution. In a longitudinal study of 244 prostitutes,
      2 of the 218 initially seronegative subjects showed anti-HCV and HCV RNA over the
      study period of 3 years. These two persons had no history of percutaneous
      exposure. Sexual transmission of HCV presents a risk for female prostitutes.

PMID- 8887033
TI  - Osteodystrophy in patients with chronic hepatitis and liver cirrhosis.
AB  - Bone mineral density (BMD) of the lumber vertebrae and factors related to bone
      metabolism were determined in patients with chronic viral hepatitis and patients
      with liver cirrhosis to clarify correlations between hepatic dysfunction,
      considered to be one of the causes of hepatic osteodystrophy, and decrease in
      bone mass. BMD of the second to fourth lumbar vertebrae was determined with a
      Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic
      system. BMD was significantly lowest in patients with liver cirrhosis, followed
      by patients with chronic hepatitis, and healthy subjects, in this order. There
      was a significantly positive but weak correlation between albumin and BMD. Levels
      of 25(OH)D and 1,25(OH)2D were significantly lower in patients with liver
      cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased
      in all patients whose cholinesterase (ChE) was below 0.3 delta pH. Urinary
      pyridinoline (Upyr) was significantly higher in the patients with liver
      cirrhosis, in whom bone mass was decreased, than in the patients with chronic
      hepatitis, whereas serum osteocalcin levels were distributed in the upper normal
      range in patients with chronic hepatitis and those with liver cirrhosis. There
      was a positive correlation between 25(OH)D and serum osteocalcin levels in
      patients with liver cirrhosis. These results indicate that osteogenesis is
      decreased and suggest that the decrease in BMD which occurs in viral liver
      cirrhosis, probably related to decreased, bone formation and slight promotion of
      bone resorption, reflects deranged hepatic function. This is the first report of
      Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver
      cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr
      and UDpyr with ChE is a novel finding.

PMID- 8887034
TI  - Effect of ethanol on mouse hepatitis virus-induced cytotoxicity.
AB  - The effect of ethanol on cells infected with mouse hepatitis virus (MHV) was
      investigated. After MHV infection of competent cells, NCTC1469, ethanol was added
      to the culture at various concentrations, and the viability of cells was measured
      using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide. To examine the
      possible involvement of the ethanol metabolite, acetaldehyde, alcohol
      dehydrogenase activity was measured in NCTC1469 cells. Ethanol alone did not show
      cytotoxicity against NCTC1469 cells at concentrations from 0.125% to 2%. After
      infection with MHV, the viability of cells decreased, and this decrease was
      further enhanced, dose-dependently, by the addition of ethanol. The activity of
      alcohol dehydrogenase in the cells was below the detectable level. The same
      phenomena were also demonstrated in cells infected with influenza virus and
      Herpes simplex virus. These results demonstrate that ethanol enhances MHV
      mediated cytotoxicity; this exacerbation of cytotoxicity by ethanol is suggested
      to be an effect common to cytopathic virus-infected cells.

PMID- 8887035
TI  - Protection by glycine against chemical ischemia produced by cyanide in cultured
      hepatocytes.
AB  - The killing of cultured hepatocytes by cyanide accelerated phospholipid
      metabolism, with a reduction in cytoplasmic pH, but did not accelerate
      proteolysis. Alkalinization of the cytoplasm by monensin, a protonsodium exchange
      ionophore, enhanced the loss of viability and acceleration of phospholipid
      metabolism caused by cyanide. Thus, acidification of the cytoplasm appears to
      protect against the toxic effects of cyanide. Glycine reduced the killing of
      hepatocytes, concomitant with reduced phospholipid metabolism. The protective
      effect of glycine neither enhanced the reduction in cytoplasmic pH nor prevented
      the depletion of adenosine triphosphate (ATP) by cyanide. The mechanism of the
      protection exerted by glycine against chemical ischemia can be attributed neither
      to changes in cytoplasmic pH nor to the prevention of ATP depletion, but appears
      to be due to other mechanisms that have yet to be identified.

PMID- 8887036
TI  - Effectiveness of glycyrrhizin for oral lichen planus in patients with chronic HCV
      infection.
AB  - Oral lichen planus (OLP), an intractable inflammatory disease characterized by a
      band-like lymphocytic invasion under the oral mucosa, is frequently associated
      with hepatitis C virus (HCV) infection. We investigated the effects of
      glycyrrhizin, which is used to treat chronic liver dysfunction, in nine patients
      with OLP who were positive for HCV antibody and HCV RNA. A control group, eight
      patients with OLP who were also positive for HCV antibody and HCV RNA, was given
      only dental cleaning. Glycyrrhizin (GL) was given intravenously, at a dose of 40
      ml (0.2% solution) daily, for 4 consecutive weeks. Six (66.7%) of the nine
      patients given GL improved clinically (P = 0.0141 vs non-GL group), suggesting
      that GL is useful in treating OLP.

PMID- 8887037
TI  - Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study
      of patients with chronic type B hepatitis. Lack of correlation with hepatitis C
      and D virus superinfection.
AB  - We investigated the frequency of HBsAg clearance and the possible role of viral
      superinfection in a long-term follow-up of 184 patients with chronic hepatitis B
      (CHB). Our subjects were 184 patients with chronic hepatitis B and the follow-up
      was 12-216 months (mean 66.2 +/- 53.7 months). The investigative methods used
      were: immunoenzymatic assays for HBV, HCV, HDV, and HIV markers; polymerase chain
      reaction (PCR) for HBV DNA; and liver biopsy and immunoperoxidase. During the
      follow-up, 20 of the 184 patients cleared serum HBsAg. A comparison of patients
      with persistent HBsAg(group I) and of those who cleared this marker (group II)
      showed a significant difference in mortality (P = 0.002) between the two groups
      and a tendency to a more severe exacerbation (flare) in group II (P = 0.07).
      Antibodies to hepatitis C and D virus as well as antibodies to HIV were equally
      distributed in both groups. Thirteen patients (7.9%) from group I, but none from
      group II, subsequently developed hepatocellular carcinoma. These results suggest
      that the frequency of spontaneous clearance of HBsAg during chronic HBV infection
      is low. No determinant factor for the clearance was found, including the presence
      of liver cirrhosis. Serum HBV DNA was undetectable by PCR after clearance in 16
      out of 17 patients.

PMID- 8887038
TI  - Effects of high-dose intraperitoneal aprotinin treatment on complement activation
      and acute phase response in acute severe pancreatitis.
AB  - Forty-eight patients with severe acute pancreatitis were treated with
      intraperitoneal lavage in a double-blind randomized multi-center trial. One group
      (aprotinin group, n = 22) was also treated intraperitoneally with high doses of
      the protease inhibitor aprotinin. In the group not treated with aprotinin
      (control group), 6 patients were operated on because of pancreatic necrosis,
      compared with none in the treated group. Complement activation and the acute
      phase response were studied with measurements of anaphylatoxin C3a, C1 inhibitor
      (C1 Inh), interleukin 6 (IL-6), and C-reactive protein (CRP). The control group
      had higher plasma levels of C3a and lower levels of C1 Inh compared with the
      aprotinin group. The differences were statistically significant for C3a but not
      for C1 Inh. Both groups had high plasma levels of IL-6 and CRP. There were no
      differences between the groups in CRP levels, but the control group had higher IL
      6 levels (not statistically significant) than the aprotinin group. This was
      caused by very high levels in the 6 patients operated on because of pancreatic
      necrosis, indicating that IL-6 could be a good plasma marker of pancreatic
      necrosis. The results also show that massive antiprotease treatment reduces
      complement activation, as illustrated by the lower C3a levels in the aprotinin
      group. The lower C1 Inh levels in the control group could have been caused by an
      increased consumption of the inhibitor.

PMID- 8887040
TI  - Strangulation ileus resulting from encasement of a loop of the small intestine by
      the great omentum, caused by abnormal adhesion.
AB  - We treated a patient with a mechanical ileus resulting from encasement of a loop
      of the small intestine by the great omentum, caused by abnormal adhesion. Apart
      from its occurrence postoperatively with laparotomy, strangulation of small
      intestine into the omentum is very rare, and its occurrence without underlying
      disease, except in children, has not been documented previously.

PMID- 8887039
TI  - Gastric antral vascular ectasia causing severe anemia.
AB  - Gastric antral vascular ectasia (GAVE) that caused continuous gastrointestinal
      bleeding is reported in a 76-year-old woman who had been treated with repeated
      blood transfusions because of severe anemia. Endoscopic examination was performed
      and diffuse speckled telangiectasia of the entire antrum was observed. Laboratory
      data showed SGOT > SGPT, decreased chE level and the increased levels of serum
      gastrin and ICG at 15 min. Anti-HCV antibody was positive. Image examination
      revealed splenomegaly. There was no family history of telangiectasia, and no
      telangiectasia was found in other organs. The diagnosis was established as GAVE
      with liver cirrhosis. Surgical resection of the distal stomach resulted in
      termination of the bleeding, and the cirrhotic changes of the surface of the
      liver were revealed at that time, providing further evidence of liver cirrhosis.
      Although the pathogenesis of GAVE is unknown, liver cirrhosis and
      hypergastrinemia are thought to be associated with the condition. Importantly,
      this condition is a cause of severe gastrointestinal bleeding in elderly
      patients.

PMID- 8887041
TI  - Right-sided ulcerative colitis.
AB  - This report describes a case of right-sided ulcerative colitis in which multiple
      shallow ulcers and erosion with symmetric luminal stenosis were distributed
      segmentally from the ascending colon to the cecum, with a skip lesion composed of
      superficial erosions in the right half of the transverse colon. Both the rectum
      and the left colon were spared at the time of onset. Biopsies taken from the
      lesions showed non-specific inflammation, while those from the rectum and sigmoid
      colon showed no abnormal findings. A 5-year follow-up study was made based on
      radiography and endoscopy. Other inflammatory bowel diseases, such as Crohn's
      disease, tuberculosis, Yersinosis, Behcet's disease, and ischemic colitis were
      all ruled out, based on the macroscopic and microscopic findings as well as the
      clinical course. To our knowledge, this is the first report of right-sided
      ulcerative colitis that has been followed for a long period.

PMID- 8887042
TI  - Development of Sjogren's syndrome during treatment with recombinant human
      interferon-alpha-2b for chronic hepatitis C.
AB  - A 63-year-old woman with type C chronic active hepatitis developed Sjogren's
      syndrome after being treated with recombinant interferon-alpha-2b. After 3
      months' interferon-alpha administration, serum levels of gamma-globulin (4.5
      g/dl) and titers of antinuclear and anti-SS-A antibodies were greatly increased,
      anti-SS-B antibody appeared, and the erythrocyte sedimentation rate was elevated.
      Although no xerostomia was exhibited, the patient experienced conjunctival
      dryness. Schirmer's test showed reduced lacrimal gland function and a gum test
      showed reduced salivary gland function. Sialography revealed scattered pools of
      retained contrast media with a diameter of around 1-2 mm. Based on these
      findings, a diagnosis of Sjogren's syndrome was made. This present case may
      provide important information regarding the pathogenesis of Sjogren's syndrome.

PMID- 8887043
TI  - Pancreatic cancer and hypercalcemia associated with von Recklinghausen's disease.
AB  - A 44-year-old man with von Recklinghausen's disease was admitted to our hospital
      presenting with left hypochondralgia. Computed tomography showed a large mass at
      the body and tail of the pancreas, with metastatic liver tumors. Endoscopic
      retrograde pancreatography revealed an obstruction of the main pancreatic duct at
      the body. In the course of the illness, the patient's serum calcium concentration
      increased gradually to 13.6 mg/dl, although bone scan with 99mtechnetium
      demonstrated no accumulation in the bones. Serum levels of parathyroid hormone
      related-protein and tumor necrosis factor were also elevated. Based on these
      findings, he was diagnosed as having pancreatic cancer with liver metastases and
      humoral hypercalcemia of malignancy associated with von Recklinghausen's disease.
      Postmortem examination revealed a solid tumor, measuring 6.0 x 6.0 x 8.0 cm, in
      the body and tail of the pancreas. Histologically, the tumor was moderately
      differentiated adenocarcinoma. The association of von Recklinghausen's disease
      with malignant neurogenic neoplasms is well established, whereas the association
      with non-neurogenic malignant neoplasm is considered to coincidental. Our current
      case suggests a possible relationship between von Recklinghausen's disease and
      pancreatic cancer.

PMID- 8887044
TI  - Mucinous biliary cystadenoma with mesenchymal stroma: expressions of CA 19-9 and
      carcinoembryonic antigen in serum and cystic fluid.
AB  - A case of mucinous biliary cystadenoma with mesenchymal stroma (CMS tumor) in a
      64-year-old woman is reported. The patient presented with acute abdominal pain
      and a palpable mass in the upper abdomen. Computed tomography and abdominal
      sonography showed characteristic multilocular cysts in the left lobe of the
      liver. Serum CA 19-9 was elevated to 108 U/ml with normal carcinoembryonic
      antigen (CEA) and alpha-fetoprotein (AFP) levels. The levels of CA 19-9 and CEA
      in the cystic fluid were high at 7430 U/ml and 576 ng/ml, respectively. The serum
      CA 19-9 returned to 35 U/ml 4 weeks after tumor resection. These corresponding
      findings of both tumor markers in the serum and cystic fluid imply that (1) CA 19
      9 and CEA both exist in the epithelial component of CMS tumors as evidenced by
      immunohistochemical stain, (2) serum CA 19-9 is a valuable marker in the
      diagnosis and monitoring of CMS, and (3) in cystic fluid, there are more
      significantly high levels of CA 19-9 in CMS compared with levels in simple cyst
      and polycystic liver disease. Therefore, measurement of CA 19-9 in cystic fluid
      and serum may be helpful in the differential diagnosis of hepatic cystic lesions.

PMID- 8887045
TI  - Primary sclerosing cholangitis associated with increased peripheral eosinophils
      and serum IgE.
AB  - Symptoms of cholestasis, including epigastralgia, fever, and jaundice, with
      marked increases in peripheral eosinophils and serum IgE in a 20-year-old man are
      reported here. Endoscopic retrograde cholangio-pancreatography (ERCP) detected
      constrictions of the bile ducts, compatible with primary sclerosing cholangitis
      (PSC). The symptoms and blood parameters of liver dysfunction were associated
      with the degree of eosinophilia and high serum IgE levels. During corticosteroid
      therapy, all of these parameters improved, and morphologic improvements of the
      bile ducts were also observed. The pathogenesis of PSC may be explained, in part,
      by the concept of hypereosinophilic syndrome or allergic reaction.

PMID- 8887046
TI  - Alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9
      producing gallbladder cancer.
AB  - We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA),
      and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels
      of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A
      63-year-old man was diagnosed with gallbladder cancer with metastases to the
      liver, based on ultrasonography and computed tomography of the abdomen showing
      multiple tumorous lesions in the liver and a thickened gallbladder wall.
      Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1
      ng/ml CEA, 11,704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ ml PIVKA II. AFP
      in the present case showed an increase in Concanavalin A-nonbinding fraction and
      an increase in Lens culinaris lectin-binding fraction by affinity column
      chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder
      cancer consisting of papillary adenocarcinoma and moderately differentiated
      tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the
      papillary adenocarcinoma portion of the primary focus and metastatic tumor cells
      in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9
      were detected mainly in the tubular adenocarcinoma portion.

PMID- 8887047
TI  - Acalculous cholecystitis: ascariasis as an unusual cause.
AB  - Migration of roundworms into the biliary tree is a well-known complication of
      Ascaris lumbricoides infestation of the intestine. Massive infestation of the
      hepato-biliary tract is uncommon but can lead to complications if not treated.
      Here, we report two cases of acalculous cholecystitis caused by ascariasis.

PMID- 8887048
TI  - Pseudoaneurysm of the cystic artery associated with upper gastrointestinal
      bleeding.
AB  - Pseudoaneurysm of the cystic artery is a cause of hemobilia, and is extremely
      rare, with only eight cases having been reported in the world literature. We
      report a case of pseudoaneurysm of the cystic artery in a 72-year-old Japanese
      man. The patient experienced epigastric pain and melena, and was found to have
      jaundice and liver dysfunction. Repeated gastroendoscopy did not reveal the cause
      of the alimentary tract bleeding; however, color-Doppler ultrasonography detected
      an aneurysm of the cystic artery in the gallbladder. Selective hepatic
      arteriography demonstrated that the posterior branch of the cystic artery was
      markedly dilated and that an aneurysm had formed in the midst of the artery. We
      diagnosed hemobilia due to the pseudoaneurysm of the cystic artery, and
      associated gastrointestinal bleeding. Cholecystectomy was performed immediately.
      Pathologically, the gallbladder showed acute calculous cholecystitis. This case
      emphasizes the importance of including hemobilia in the differential diagnosis
      whenever gastrointestinal bleeding is associated with signs of biliary disorder;
      color-Doppler imaging is a favorable modality for the diagnosis of pseudoaneurysm
      of the cystic artery.

PMID- 8887049
TI  - Induction of gastric ulcer and intestinal metaplasia in mongolian gerbils
      infected with Helicobacter pylori.

PMID- 8887050
TI  - Pyloric antral inhibition of gastrin release.
AB  - Inconsistencies and omissions in current explanations for the well known
      depressions of gastric acid secretion and blood gastrin levels following
      acidification by antral stimulants are discussed. Evidence is presented which
      favors a reciprocal sensitivity relationship between the fundic mucosa and the
      antral G cells, such that blood gastrin levels rise when the secreting fundic
      mucosa is compromised and acid secretion in response to exogenous gastrin is
      increased when G cells are depressed or reduced. The functional connections
      between the two phenomena are considered to be nervous.

PMID- 8887051
TI  - Disruption of cytokine signaling in lymphoid development: unique contributions of
      the common cytokine gamma chain and the Jak3 kinase.

PMID- 8887052
TI  - Diverse effects of tumor necrosis factor-alpha on three subclones from human
      myelomonocytic leukemia cell line ME-1 exhibiting different differentiation
      stages.
AB  - The effects of tumor necrosis factor-alpha (TNF-alpha) were examined in three
      subclone cells from human myelomonocytic leukemia cell line ME-1. These three
      subclone cells exhibit different differentiation stages of the myelomonocytic
      lineage. TNF-alpha exerted a growth-suppressive effect on the least mature
      subclone cells, ME-F2 cells. On the other hand, TNF-alpha induced the most mature
      ME-F1 cells and intermediate ME-F3 cells to differentiate along the monocytic
      pathway. TNF-alpha also enhanced interferon-gamma (IFN-gamma)-induced complement
      C2 production by ME-F1 and ME-F3 cells but did not affect production by
      differentiated ME-F1 and ME-F3 cells. These results suggest that the diversity of
      the effects of TNF on subclone cells from ME-1 depends on the stage of cell
      differentiation.

PMID- 8887053
TI  - Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6
      expression in a rat mononeuropathy model.
AB  - It has been suggested that neuroimmunologic mechanisms may be involved in the
      development and maintenance of neuropathic pain. To further address this concept,
      the immunoreactive spinal expression of the pro-inflammatory cytokine,
      interleukin-6 (IL-6), was determined in the mononeuropathy model in the rat,
      sciatic cryoneurolysis (SCN). This well-established animal model expresses
      behaviors suggestive of neuropathic pain in humans. Immunohistochemical
      localization in the spinal cord was determined at 3, 7, 14, 21, 35, and 120 days
      after SCN (n = 6 per time point). Immunoreactive IL-6 increased incrementally in
      the substantia gelatinosa and motoneurons over time following SCN as compared
      with normal rats. In an additional study, recombinant human IL-6 was administered
      intrathecally to normal and previously SCN-lesioned rats. Intrathecal IL-6
      produced touch-evoked allodynia (increased sensitivity to a nonnoxious stimulus)
      in normal rats and thermal hyperalgesia (increased sensitivity to a noxious
      stimulus) in previously lesioned SCN rats. These results provide evidence that IL
      6 may be involved in the cascade of events leading to the development and
      maintenance of behaviors suggestive of neuropathic pain following peripheral
      nerve injury.

PMID- 8887054
TI  - Interferon-gamma enhances megakaryocyte colony-stimulating activity in murine
      bone marrow cells.
AB  - We have demonstrated previously that interferon-gamma (IFN-gamma) accelerates
      platelet recovery in mice with 5-FU induced-marrow aplasia in vivo. However, the
      mechanism for the regulation of megakaryocyte development induced by IFN-gamma in
      bone marrow cells in vivo remains unknown. To further study the effects of IFN
      gamma on megakaryocyte development, various steps during IFN-gamma-mediated
      accelerated differentiation of the megakaryocytes were investigated in serum-free
      cultures of murine bone marrow cells in vitro. IFN-gamma markedly induced
      acetylcholine esterase (AChE) activity, a marker of murine megakaryocytic cells,
      accompanied by increased colony formation of the megakaryocyte lineage. A
      prominent increase in megakaryocyte number was observed after IFN-gamma
      treatment. All of these effects were dependent on the presence of IL-3, and,
      therefore, these results suggest that IFN-gamma acts as a megakaryocyte
      potentiator (Meg-POT). However, IFN-gamma did not enhance megakaryocyte
      maturation with respect to increase in cell size. The effects of IFN-gamma on
      megakaryocyte maturation were similar to those observed after treatment with
      higher doses of IL-3 alone. Meg-POT is defined as a factor that induces
      megakaryocyte maturation. Since IFN-gamma enhanced IL-3-dependent megakaryocyte
      colony formation and proliferation rather than megakaryocyte maturation, the
      effects on megakaryocyte development, which were induced by IFN-gamma treatment,
      seem to be different from the effects of a Meg-POT. We, therefore, propose a new
      function for IFN-gamma as an enhancer of megakaryocyte colony-stimulating factor
      activity. The effect of IFN-gamma in vitro appears to correlate well with the
      acceleration of platelet recovery in vivo.

PMID- 8887055
TI  - Interferon-alpha-induced human lupus inclusions and p36 protein in cancer and
      AIDS.
AB  - Previous work showed that IFN-alpha induced the autoimmune-associated lupus
      inclusions (LI) in all 16 umbilical cord mononuclear cell samples from healthy
      mothers. In contrast, IFN-alpha induced LI and the LI-associated protein, p36, in
      only 2 of 16 human B lymphoblastoid cell lines. Resistance of these 14 cell lines
      to form LI and p36 may be due to their stage of development or differentiation or
      their transformed state. We sought to determine whether aging, neoplastic
      transformation, and HIV infection affected the observed IFN-alpha induction of LI
      in cord blood mononuclear cells. Expression of LI and p36 was investigated in
      PBMC on IFN-alpha chemotherapy and on culturing IFN-alpha with PBMC samples
      prepared from healthy adults and AIDS patients. The IFN-alpha induction of LI
      (detected by electron microscopy) or p36 (detected by two-dimensional gels) in
      all of the PBMC samples from these individuals was indistinguishable from the
      cord blood mononuclear cell response. Furthermore, induction of p36 and LI was
      not a good indicator of effective IFN-alpha chemotherapy. It may be consequential
      for autoimmunity induced by IFN-alpha in cancer, AIDS, and systemic lupus
      erythematosus (SLE). An essential biologic role for p36 and LI is suggested by a
      highly homologous p36 gene in the invertebrate Caenorhabditis elegans.

PMID- 8887056
TI  - Human interferon reduces surface expression but not total production of herpes
      simplex virus type 1 glycoproteins gC and gE in heterologous hamster cells.
AB  - The effect of interferon (IFN) on herpes simplex virus type 1 (HSV-1)-induced
      glycoproteins gC and gE was investigated in a heterologous IFN/cell model. In
      this model, the effect on surface expression of the glycoproteins could be
      studied separately from the effect on virus multiplication. Pretreatment of baby
      hamster kidney cells (BHK) with heterologous human leukocyte IFN suppressed
      surface expression of HSV-1-encoded gC and gE but had no influence on total
      production of the glycoproteins. This was in contrast to the effect on human
      embryonic fibroblast cells (HE) (homologous IFN and cells), where surface
      expression as well as total production of glycoproteins were reduced. The surface
      expression was demonstrated by antibody-sensitized monodisperse polystyrene
      beads, and immunoblotting and two-dimensional electrophoretic analysis of
      radioisotope-labeled proteins were used to study the total production.

PMID- 8887057
TI  - Mechanism of enhancement of the antiviral action of interferon against herpes
      simplex virus-1 by chloroquine.
AB  - Using double immunofluorescence, we have shown previously that interferon (IFN)
      treatment inhibits the transport of herpes simplex virus-1 (HSV-1) gD from the
      Golgi complex to the plasma membrane in the virus infected and gD cDNA
      transfected LMtk-cells. In the present study, we quantitated the gD protein on
      the cell surface and localized the gD protein in the trans-Golgi network (TGN).
      The results showed 10-fold less fluorescence for the gD protein on the cell
      surface in IFN-treated LMtk-cells. Subcellular fractionation studies demonstrated
      that gD was associated with TGN-enriched membranes. Gold labeling for DAMP
      distribution using electron microscopy showed that IFN raised the pH of TGN. IFNs
      induced alkalinization of TGN may be related to the block in the transport of HSV
      1 gD. Earlier we reported that a subeffective dose of chloroquine (CHL) or IFN
      does not change the pHi. However, both CHL and IFN together raise the pHi
      significantly. To study the biologic significance of the finding, the effect of
      these subeffective doses of IFN and CHL on the antiviral activity and the
      transport of the gD protein was studied. Results suggested that CHL enhance the
      antiviral activity of IFN against HSV-1 and concomitantly increase the inhibition
      of HSV-1 gD transport. This IFN-induced increase in pHi of the TGN may also
      explain the inhibitory effect of IFN reported on the terminal steps of some of
      the enveloped viruses.

PMID- 8887058
TI  - Hypomutable potential accompanying interferon-alpha resistance in a human cell
      line, IFr, derived from interferon-alpha-sensitive and hypermutable RSa cells.
AB  - A human cell line, IFr, established from RSa cells, is a variant with increased
      resistance to cell proliferation inhibition (CPI) by human interferon (HuIFN)
      alpha. The parent RSa cells are also hypermutable after irradiation with far
      ultraviolet light (UV), as assessed by two different methods: cloning efficiency
      of ouabain-resistant (OuaR) mutants and K-ras codon 12 mutation in genomic DNA
      identified by polymerase chain reaction (PCR) following differential dot-blot
      hybridization. In the present study, IFr cells were found to be hypomutable: Less
      than 1 OuaR mutant per 10(4) surviving cells after UV (0-12 J/m2), in contrast to
      1-53 OuaR mutants per 10(4) survivors in RSa cells, and no-detectable K-ras codon
      12 mutation at any doses tested. However, IFr cells, when cultured with medium
      containing the protease inhibitor antipain after UV irradiation showed
      hypermutability to almost the same extent as RSa cells, as determined by both
      phenotypic and genetic mutation analyses. These results, together with the
      previous finding of antipain-sensitive protease induction in UV-irradiated or
      HuIFN-alpha-treated IFr cells, suggest that antipain-sensitive proteases or
      cellular functions or both may be involved in not only HuIFN-alpha resistance but
      also hypomutability of IFr cells.

PMID- 8887059
TI  - Modulation of human papillomavirus type 16 mRNA in cervical invasive carcinoma
      patients by interferon-alpha therapy.
AB  - Mechanisms by which interferon produces papilloma regression remain largely
      unknown. We analyzed biopsies from three cervical invasive carcinoma patients
      treated with interferon-alpha (IFN-alpha) administered both topically and i.m.
      for 15 days. All specimens contained human papillomavirus (HPV-16) DNA as
      determined by polymerase chain reaction using specific HPV-16 E7 primers.
      Interestingly, in two patients. HPV-16 mRNA expression was reduced (44% and 67%,
      respectively) after IFN treatment. Upregulation of 2-5 A synthetase and PKR mRNA
      levels were indicative of the IFN effect. A larger study should be initiated to
      see whether IFN-alpha modulates the HPV-16 mRNA levels in tumor biopsies from
      cervical carcinoma patients.

PMID- 8887060
TI  - Comparative study on the effect of signal peptide codons and arginine codons on
      the expression of human interferon-alpha 1 gene in Escherichia coli.
AB  - Human interferon-alpha 1 (HuIFN-alpha 1) gene containing signal peptide codons is
      poorly expressed in bacteria, and this is explained by the presence of clusters
      of rare (AGG) arginine codons in its structure. In this study, we have
      constructed a series of modified HuIFN-alpha 1 genes to study the effect of both
      residual signal peptide codons and clusters of AGG codons on gene expression in
      Escherichia coli cells. Our results showed that substitution of preferential for
      rare arginine codons in two clusters did not affect the yield, whereas deletion
      of the signal peptide codons led to a 10-fold increase in the yield of
      recombinant protein. To understand the mechanism of interference of gene
      structure on the expression of the HuIFN-alpha 1 gene in vivo, both the level and
      stability of HuIFN-alpha 1 mRNA were measured. The amount of HuIFN mRNA increased
      almost five times on deletion of the signal peptide codons from HuIFN-alpha 1
      gene constructs (containing AGG clusters or not). The stability of mRNA obtained
      from all gene constructs was shown to be the same (half-life of 60 +/- 5 secs),
      indicating that the signal peptide codons interfere with both the efficiency of
      transcription of the HuIFN-alpha 1 gene and translation of its mRNA.

PMID- 8887061
TI  - Treatment of ME180 cells with interferon-gamma causes apoptosis as a result of
      tryptophan starvation.
AB  - Indoleamine 2'3 dioxygenase (INDO), the rate-limiting enzyme in the catabolism of
      the essential amino acid L-tryptophan, is induced in many cell lines following
      interferon gamma (IFN-gamma) treatment. The induction of this enzyme has been
      associated with the antiparasitic and cytotoxic activities of human IFN-gamma.
      DNA analysis coupled to morphologic studies indicated that ME180 cells underwent
      apoptosis within 48 h of treatment with IFN-gamma. We hypothesized that apoptosis
      results from L-tryptophan starvation following INDO induction. This was confirmed
      by the prevention of apoptosis on adding back tryptophan to IFN-gamma-treated
      cells and the induction of apoptosis by removing tryptophan from the medium in
      the absence of IFN-gamma.

PMID- 8887062
TI  - Jacob Markowitz Award. Georg Heberer, Dr. med.

PMID- 8887063
TI  - Jacob Markowitz Award. Henry Swan II, MD.

PMID- 8887064
TI  - Considerations of specific pathogen-free swine (SPF) in xenotransplantation.
AB  - The purpose of this manuscript was to introduce the complexities involved in
      defining both the appropriate health status and the management programs for SPF
      swine as they may relate to xenotransplantation. One factor that must always be
      considered in using swine is that they are considered agricultural animals
      regardless of their purpose and are regulated as such by municipalities, states,
      and countries. There are nonflexible regulations related to the interstate
      transportation of swine and even greater hurdles to international transportation.
      For example, I tried unsuccessfully for three years to transport a single
      breeding animal with a congenital heart defect to collaborators in the United
      Kingdom. Bureaucratic factors on both sides of the Atlantic proved insurmountable
      because the regulations were formulated for economic and isolation purposes and
      no exceptions could be granted for research animals. Another factor to be
      considered is the designation of SPF swine, which in this species has a specific
      proprietary connotation. If the finalized program for production of swine for
      xenotransplantation proves to be different from the already established SPF
      program, then a different designation may have to be used. For example, a term
      like "xenografic defined flora (XDF)" swine could be used to avoid confusion with
      the already established registry. If xenotransplantation using swine becomes a
      reality, then it is important that the parameters used to select such animals be
      defined in advance. It is unlikely that conventionally reared animals of
      uncertain health status will be widely accepted because of legal and ethical
      considerations. Likewise, I do not believe that the use of swine for
      xenotransplantation will be able to avoid the regulatory measures already in
      place for laboratory animals. The multidisciplinary approach to the problem
      initiated by the Institute of Medicine workshop is the most appropriate mechanism
      for resolving the issues.

PMID- 8887065
TI  - Use of regression analysis and flow cytometry for determining levels of mixed
      semiallogeneic immune chimerism.
AB  - It has been shown that tolerance or specific immunologic nonresponsiveness in
      various lymphohemopoietic transplant models can be associated with the
      development of mixed lymphoid chimerism. As a specific example, composite tissue
      (limb) allografts were studied as a model for vascularized bone marrow
      transplantation (VBMT) and it was demonstrated that development of stable
      cellular immune chimerism is associated with long-term allograft survival.
      Recently, studies were initiated using a new parental to hybrid VBMT model, but
      the detection of donor cells is complicated, due to the fact that they share one
      parental allotypic determinant. Therefore, regression analysis with a flow
      cytometric immunofluorescent staining assay was evaluated for the assessment of
      cellular lymphoid chimerism in donor parental to hybrid (P-->F1)
      lymphohemopoietic transplant models. Standard curves consisting of known mixed
      populations of parental donor (Lewis, LEW) and hybrid host F1 (Lew x BN, LBN)
      lymphocytes were established. Standard curves were analyzed by linear regression
      statistics and excellent coefficients of determination (r > .881) were obtained
      for all standard curves. A highly statistically significant (p < .016) linear
      relationship between level of donor cell chimerism (independent variable) and
      percent stained (dependent variable) was determined. The technique was then
      evaluated using the parental to hybrid VBMT model. Levels of donor LEW lymphoid
      chimerism in all VBMT LBN recipients were successfully assessed by regression
      analysis and inverse prediction using distinct recipient allodeterminant markers.
      In conclusion, this technique was proven to be reliable and accurate for the
      detection of of chimerism in parental to F1 lymphohemopoietic allograft models.

PMID- 8887066
TI  - Effects of anti-inflammatory agents on hydrochloric acid-induced pulmonary
      injury.
AB  - To determine the effects of anti-inflammatory agents on hydrochloric acid lung
      injury, the heart and lungs were harvested from rats, placed in a lung chamber,
      constant flow perfused with whole blood, and ventilated. The following
      experiments were conducted: observation alone; intratracheal injection of normal
      saline; intratracheal hydrochloric acid; and intravenous meclofenamate or
      indomethacin before intratracheal hydrochloric acid. Wet-to-dry lung weights were
      measured. Peak airway pressures increased immediately (p < .001 vs. baseline;
      ANOVA) in all intratracheal groups, hydrochloric acid producing even greater (p <
      .05) increases than saline-effects unaltered by meclofenamate or indomethacin.
      The increased (p < .001 vs. baseline) 2-h pulmonary artery pressures in
      hydrochloric acid-treated groups were unaltered by meclofenamate or indomethacin.
      All hydrochloric acid-treated groups demonstrated increases (p < .05) in weight
      that were unchanged by meclofenamate or indomethacin. These data suggest that the
      beneficial effects of these medications described elsewhere, using a variety of
      in vivo lung injury experimental models, may be attributed to their experimental
      design, or to contributions from organs/systems outside the pulmonary circuit.

PMID- 8887067
TI  - Bacterial translocation after mesenteric ligation in dogs.
AB  - These experiments were designed to determine the relationship between
      translocation of Escherichia coli and viability of ischemic small bowel. Twenty
      beagles were gavaged with 14C-labeled E. coli at two time intervals (3 and 24 h)
      prior to ligation of the blood supply to a 40-cm segment of ileum. Mesenteric
      lymph node (MLN) biopsies and bacterial cultures of the peritoneal fluid,
      peripheral arterial blood, and splanchnic venous blood were taken immediately
      prior to ligation and 24 h later both before and after the ischemic bowel was
      resected and anastomosed. Biopsies of each resection margin were taken to measure
      translocation of E. coli into the bowel wall. Several hemodynamic hemodynamic
      parameters were also measured before and 24 h after ligation. Seven of the 20
      dogs died of further bowel necrosis. In survivors A-alpha DO2 was significantly
      decreased 24 h after mesenteric ligation vs. preligation, whereas in dogs that
      died DO2 was significantly increased after ligation vs. preligation. The
      incidence of mesenteric venous cultures positive for E. coli was significantly
      higher 24 h after ligation vs. preligation. However, there was no correlation
      between survival and the incidence of positive E. coli cultures in the blood or
      peritoneal fluid. Mean MLN counts were significantly higher in dogs gavaged at 3
      h vs. those gavaged 24 h prior to laparotomy. However, there was no correlation
      between survival and translocation into either the bowel wall or MLN at either
      time interval. Viability of ischemic small bowel in this canine model was not
      affected by translocation of E. coli. Hemodynamic parameters that are altered
      during the course of sepsis also did not correlate with survival.

PMID- 8887068
TI  - Transorbital approach to the porcine pituitary.
AB  - A transorbital approach to the pituitary gland is described in domestic swine
      weighing between 40 and 70 kg. A transpalpebral eye exenteration is performed and
      the optic canal is enlarged caudally, using a bone drill. An operating microscope
      is used to improve visualization of the surgical site as the pituitary stalk and
      anterior pituitary are exposed to the level of the optic chiasm. This approach
      exposes the pituitary sufficiently to perform either a hypophyseal stalk
      transection or a hypophysectomy or to implant cannulas for hypothalamic
      hypophyseal portal blood sampling. This technique has been performed in more than
      50 pigs without major complications. Postoperative recovery has been rapid and
      uneventful. The transorbital approach is a significant refinement of the frontal
      craniotomy and cerebral elevation technique previously described in the pig, and
      results in shortened surgery time, minimal brain manipulation, and greatly
      decreased morbidity.

PMID- 8887069
TI  - Secretory phospholipase A2 levels in rat small bowel.
AB  - Preliminary studies on ischemia/reperfusion injury in transplanted small bowel
      grafts showed that secretory phospholipase A2 (sPLA2) may play a substantial role
      by breaking down membrane phospholipids. This study sought to determine the
      normal values of sPLA2 in the rat small bowel as a function of site and length as
      a baseline for future studies. The entire small bowel of male Lewis rats (200 g)
      was flushed with normal saline to eliminate solid contents. In group 1, the
      entire small bowel was divided into 5-cm segments (numbered 1-9), which were snap
      frozen and processed the same day for sPLA2. In group 2, a 25-cm segment of bowel
      (corresponding to segments 2-6 in group 1) was harvested from each animal, snap
      frozen, and immediately processed for sPLA2. To assess the effect of bowel
      storage on enzyme content, group 3 and group 4 grafts were stored for 7 and 14
      days, respectively, at -85 degrees C prior to processing. All samples were
      homogenized in buffer, extracted with H2SO4 and assayed for sPLA2 activity using
      [1-14C]oleate-labeled autoclaved Escherichia coli as substrate. Results were
      analyzed statistically by ANOVA. sPLA2 activity rose from 85.46 +/- 14.46%
      hydrolysis/min fraction-1 in segment 1, to 476.38 +/- 176.75% hydrolysis/min
      fraction-1 in segment 9. The increase was linear and statistically significant (p
      < .0001). There was no significant difference in enzymatic activity between
      groups 2, 3, and 4. Group 2 activity was 263.02 +/- 43.74% hydrolysis/min
      fraction-1. This value was not statistically different from the mathematically
      calculated mean of segments 2-6 in group 1 (237.75). The results show that (1)
      sPLA2 activity increases predictably with distance from the ligament of Treitz
      (2) storage at -85 degrees C does not affect sPLA2, activity, and (3) 25-cm
      grafts may be evaluated in toto with reproducible baseline enzyme activity. Given
      the variability of enzyme activity along the course of the rat small bowel, it is
      imperative that exact location be identified in any studies evaluating sPLA2
      activity.

PMID- 8887070
TI  - Effect of flushing pressure on rat small bowel transplants.
AB  - Excessive flushing pressure in rat small bowel transplants may cause graft
      failure, but the optimal pressure for manual flushing has not been established.
      The goal of this study was to determine a safe yet effective pressure for
      intravascular graft flushing and to evaluate the consequences of higher
      pressures. The "usual" manual flush was found to be at a pressure of
      approximately 40 mm Hg. After harvest, grafts were flushed manually with
      heparinized normal saline solution while connected to a transducer. Two groups of
      25-cm jejunal grafts (n = 5 each) were harvested from Lewis rats (200 g) on a
      pedicle of superior mesenteric artery and vein. Group 1 grafts underwent 3
      successive flushes at 50, 100, 200 mm Hg, respectively. After each flush, full
      thickness biopsies were obtained for light and transmission electron microscopy.
      Two grafts underwent syngeneic small bowel transplantation (SBTx), and biopsies
      were taken after reperfusion. Group 2 grafts were flushed at 50 mm Hg and
      biopsies were obtained. All grafts underwent SBTx and biopsies as in group 1.
      After flushing at 50 mm Hg. biopsies were essentially normal. When flushed at 100
      mm Hg, there was pronounced epithelial separation with dilatation of the core of
      the villus. Flushing at 200 mm Hg resulted in complete separation of the villi,
      with occasional disruption in the crypts. All group 1 transplanted grafts were
      grossly nonviable immediately after reperfusion, while transplanted grafts in
      group 2 were grossly normal. The findings were consistent within each group and
      the difference between groups was statistically significant (0 vs. 100%). The
      results suggest that flushing pressures of 50 mm Hg in rat SBTx provide optimal
      evacuation of blood with minimal, reversible tissue injury. Higher pressures
      cause progressive histologic damage and may produce nonviable grafts. Flushing
      pressures in the rat model of SBTx should therefore be maintained at
      approximately 50 mm Hg.

PMID- 8887071
TI  - Effectiveness of fibrin glue in the reduction of postoperative intrapericardial
      adhesions.
AB  - The hemostatic properties of fibrin sealant have been well described. Previously
      published reports have attempted to clarify the possible role of fibrin glue in
      the inhibition of the formation of intrapericardial adhesions following cardiac
      surgery. Earlier work hypothesized that fibrin glue may reduce the severity of
      postoperative adhesions and that the use of autologous fibrin glue may have
      similar effects, without the risks that accompany homologous blood products. Six
      juvenile farm pigs were utilized to test this hypothesis. Conventional fibrin
      glue and single-donor fibrin glue were tested in open-heart surgery. This
      experimental model was also reexamined and found to be of significant utility in
      simulating adult reoperative cardiac surgery. The fibrin glue subjects were
      universally easier to reoperate due to fewer adhesions, as demonstrated grossly
      and histologically. The single-donor fibrin glue had no significant advantage on
      adhesion formation, when compared to the conventional fibrin glue group, but the
      ramifications of formulating fibrin glue in this fashion offer a significant
      benefit toward the complete use of autologous blood products in open-heart
      surgery.

PMID- 8887072
TI  - Keratin 14 and 19 expression in normal, dysplastic and malignant oral epithelia.
      A study using in situ hybridization and immunohistochemistry.
AB  - Specific mRNA and protein for two major keratins, K14 and K19, were investigated
      in normal, dysplastic and malignant oral epithelia by combined in situ
      hybridization and immunohistochemistry. In normal epithelia, K14 mRNA and protein
      were present almost exclusively in the basal layer of non-cornified, and in rete
      processes of cornified, sites. Dysplastic epithelium showed irregular extension
      of the K14 transcript and protein into superficial cells. In squamous cell
      carcinoma (SCC), K14 transcript was abundant in most samples whilst in one poorly
      differentiated carcinoma mRNA but no protein was detected. K19 mRNA and its
      protein were present predominantly in basal cells of noncornified epithelium,
      whereas in cornified epithelium only mRNA was detected. In dysplasias, K19
      transcript was detected in all specimens but its protein was absent in most
      cases. Even more variations of K19 expression were observed in SSC. These
      findings indicate differences in the control of expression of K14 and K19 in
      normal epithelia and show that regulation is further disturbed during dysplastic
      change and malignancy.

PMID- 8887073
TI  - Alterations of tumor suppressor genes and the H-ras oncogene in oral squamous
      cell carcinoma.
AB  - The frequencies of mutations in the adenomatous polyposis coli (APC). p53, and
      p16 (MTS1; multiple tumor suppressor 1/CDK4I; cyclin-dependent kinase 4
      inhibitor) tumor suppressor genes were investigated in 23 oral squamous cell
      carcinomas (SCCs). Loss of heterozygosity (LOH) at the retinoblastoma (Rb) gene
      locus and on chromosomes 3p (VHL; von Hippel-Lindau disease tumor suppressor gene
      locus), 5q (APC) and 9p (p16), and H-ras oncogene mutations were also studied in
      the same samples. Techniques employed were polymerase chain reaction single
      strand conformation polymorphism (PCR-SSCP), DNA sequencing and PCR
      microsatellite analyses. Mutations of the p53 gene were detected in 26% (6/23) of
      the tumor specimens. APC and p16 were not mutated in any of the 23 oral SCCs
      studied. LOH was detected in 17% (2/12 informative cases) at the Rb, in 33%
      (4/12) on 3p, in 17% (4/ 23) on 5q and in 30% (3/10) on 9p. Mutations of the H
      ras gene were detected in 9% (2/23). The only correlation between these genetic
      alterations and clinicopathologic characteristics was that mutations of the p53
      gene were detected more frequently in oral SCCs with lymph node metastasis than
      in those without it (P < 0.05). These results demonstrate that mutations of the
      p53 gene and LOH on 3p and 9p frequently occur in oral SCC and play important
      roles in the development and/or progression of this common malignancy.

PMID- 8887074
TI  - Implantation of Candida albicans and other Candida species in the oral cavity of
      rats.
AB  - The carriage of five Candida species in the mouths of normal and
      sialoadenectomised rats was determined for periods up to 30 days after
      inoculation into the oral cavity. In both test and control animals, Candida
      albicans was the species recovered in greatest quantities at all periods,
      followed by C. parapsilosis and C. tropicalis. In contrast, C. guilliermondii and
      C. krusei were isolatable only in small numbers and only from the 1st up to the
      5th day; they were not present thereafter. Sialoadenectomy favoured oral
      colonisation only by C. albicans (P < 0.05) and did not influence the carriage of
      the other species.

PMID- 8887075
TI  - Adverse reactions in the oral mucosa associated with anterior composite
      restorations.
AB  - This is a descriptive study of patients with symptomatic lichenoid-like reactions
      of the lips in contact with composite restorations (n = 12). Clinically, the
      lesions appeared as symptomatic single or multiple erythematous areas that
      included white papules. Candida was found by cultivation or histopathological
      examination in 7 of the lesions. Patch testing (n = 7) did not reveal any
      reactions to composite components, except for one patient who showed a delayed
      hypersensitivity reaction to formaldehyde. Replacement of existing dental
      materials parallel to antifungal treatment resulted in healing or significant
      improvement in 7 of 9 patients. This study shows that resin components can be
      associated with adverse reactions in the oral mucosa of the lips and that these
      reactions may be accompanied by an infection with Candida.

PMID- 8887076
TI  - Oral mucosal lesions in experimental graft-versus-host disease: morphological and
      immunohistochemical characterization of infiltrating cells.
AB  - To facilitate recognition of the oral mucosal lesion that develops in rats with
      graft-versus-host disease (GVHD) induced by injecting spleen cells of parental
      strain rats (Brown Norway) into non-irradiated (Brown Norway x Lewis) F1 hybrid
      rats, we followed the development of the tongue lesion histologically and
      immunohistochemically. This assessment revealed an increase in the number of MHC
      class II+ cells with dendritic shape in the lamina propria to be the earliest
      stage of the tongue lesions in GVHD rats. The subsequent mononuclear cell
      infiltration with epithelial cell destruction, characteristic of GVHD, consisted
      of CD8+ cells and macrophages. Our findings seem to indicate that MHC class II+
      cells with dendritic shape may provide antigen presentation in the induction of
      local immunological responses, including tissue destruction, by CD8+ cells and
      macrophages in the tongue of GVHD rats.

PMID- 8887077
TI  - Expression of the E-selectin gene in human gingival epithelial tissue.
AB  - E-selectin is an adhesion molecule, expressed by cytokine-activated endothelial
      cells, that participates in the binding of neutrophils. Recent studies in our
      laboratory documented binding of the E-selectin-specific monoclonal antibody
      H4/18 to keratinocytes in inflamed human oral mucosa, particularly gingival
      epithelium. To determine whether this immunoreactivity was due to expression of
      authentic E-selectin, the presence of E-selectin mRNA in gingival epithelium was
      analysed using the polymerase chain reaction (PCR). Reverse transcription of
      epithelial RNA and amplification of cDNA with E-selectin-specific primers
      resulted in the formation of a 178 nucleotide PCR product identical to that
      obtained from cytokine-activated endothelial cells. Sequencing of the PCR product
      revealed 100% homology between epithelial and endothelial E-selectin fragments.
      Epithelial preparations did not contain mRNA for von Willebrand factor, excluding
      the possibility of contamination by endothelial cells. These results confirm
      immunohistochemical studies of E-selectin immunoreactivity in human oral mucosa
      and demonstrate that E-selectin expression is not confined to endothelium.

PMID- 8887078
TI  - Radicular cysts are involved in the recruitment of osteoclast precursors.
AB  - In consideration of the close relationship between radicular cysts and alveolar
      bone, it is important to evaluate the potential involvement of the neighbouring
      bone tissue in such lesions. In the present study, using cytochemical,
      immunocytochemical and morphological analyses, presumptive osteoclast precursors
      were revealed in the connective tissue of radicular cyst capsules. The
      osteoclastic nature of these cells was postulated by their positive staining for
      the enzyme tartrate-resistant acid phosphatase (TRAP) and by the expression of
      vitronectin receptor (VnR) on their cell surface. However, these cells did not
      express the vacuolar-type proton pump, suggesting that they may represent early
      osteoclast precursors infiltrating the cyst capsule. Cysts also contained
      activated small blood vessels whose endothelial cells expressed the VnR. This
      integrin receptor is important in the adhesion of preosteoclasts to the
      endothelial lining, a necessary step for their emigration out of the vasculature.
      Therefore, the intracystic vessels could represent a substrate for preosteoclast
      recruitment. These precursor cells may then reach the perialveolar bone surface
      and contribute to bone demolition together with those recruited by the resorbing
      surfaces. The bone-destroying potential of radicular cysts was confirmed by the
      presence of numerous osteoclasts with large resorption areas on the perialveolar
      bone surfaces exposed to the cyst capsules. The resorbed surfaces were usually
      located around the vascular canals of the Haversian systems.

PMID- 8887079
TI  - Analysis of immunoglobulin-synthesizing cells in human dental periapical lesions
      by in situ hybridization and immunohistochemistry.
AB  - Immunoglobulin (Ig) kappa (kappa) and lambda (lambda) light chain mRNA-expressing
      cells were investigated by in situ hybridization (ISH) to assess the local
      humoral immune response in human dental periapical lesions. Twenty-seven biopsy
      samples (17 periapical granulomas and 10 radicular cysts) were examined. Both
      types of light chain mRNA-positive cells were detected in formalin-fixed/paraffin
      embedded tissue sections in all samples. Plasma cells showed weak to strong
      cytoplasmic staining with both probes and background staining was negligible. The
      ISH methodology is specific and sensitive in detecting Ig light chain mRNAs and
      retains cell morphology well. kappa to lambda ratios showed moderate variability
      for both granulomas and cysts (mean = 1.66 +/- 0.85 SD, 1.47 +/- 0.51,
      respectively). There was no significant difference in light chain distribution
      between granulomas and cysts. Ig kappa and lambda light chain proteins were also
      studied by immunohistochemistry (IHC) but the results were disappointing due to
      excessive background staining. This study confirms that Ig is locally produced in
      periapical lesions and that the ISH method localises Ig light chain-containing
      cells better than IHC. The wide variability in kappa/lambda ratio may support the
      concept of non-specific multibacterial infection in these lesions.

PMID- 8887080
TI  - Sialadenoma papilliferum: an immunohistochemical study of five cases.
AB  - Sialadenoma papilliferum (SP) is a rare, benign, salivary gland tumor which most
      commonly arises in the palate. It has a typical biphasic gross and microscopic
      appearance which distinguishes this tumor from other papillary-like tumors of the
      oral cavity. This study reports the clinico-pathologic features of 5 new cases
      and analyzes the morphologic and immunophenotypic features of their cell
      components. Adluminal epithelial cells of duct-like structures appeared
      immunoreactive to cytokeratin 19 and to S-100 protein antibodies; two subsets of
      basally-located cells were identified by means of immunohistochemistry. One cell
      subset expressed cytokeratin 14, S-100 protein, GFAP, vimentin and smooth muscle
      actin immunoreactivity; this antigenic profile is consistent with myoepithelial
      differentiation. The second subset of basal cells expressed cytokeratins 13 and
      14 reactivity but it was negative to all other antibodies. Anti-CD 1a and anti-S
      100 protein antibodies revealed distinct cells with dendritic processes which
      resembled Langerhans cells. The extralobular location of SP, the continuity
      between neoplastic duct-like structures and the surface epithelium along with the
      presence, within the excretory ducts adjacent to the tumour, of lesions which
      possibly precede the development of SP give further strength to the hypothesis of
      an origin from the excretory ducts of this tumor. Langerhans cells seem to be
      present in sialadenoma papilliferum but their role in this tumor is still
      unclear.

PMID- 8887081
TI  - Hypophosphatasia affecting the permanent dentition.
AB  - Reports on dental abnormalities in connection with hypophosphatasia almost
      exclusively describe changes in primary teeth. A 23-year-old man with
      hypophosphatasia, first diagnosed at the age of 8 months, is described;
      histologically and radiographically verified signs of the condition were present
      in the permanent dentition. The findings included a reduced level of the marginal
      alveolar bone supporting the upper central incisors, which had to be extracted.
      The molars displayed large coronal pulp chambers. Histologically, the upper
      incisors demonstrated abnormal root cementum, with areas of dentin resorption, as
      well as disturbances of the mineralization of the coronal dentin. The patient
      also had signs of abnormal root resorption of molars. The potential involvement
      of permanent teeth puts children with hypophosphatasia at risk of developing oral
      complications during adolescent and adult life.

PMID- 8887082
TI  - Cytological and cytochemical investigations on granular cells in oral lichen
      planus.
AB  - Two biopsy specimens showed unusual histology characterized by features
      consistent with resolving oral lichen planus and voluminous, finely granular
      cells in the lamina propria, resembling the cells of granular cell tumour.
      Immunocytochemistry and lipid-pigment histochemistry indicated that the granular
      cells are macrophages of low proliferative activity laden with early ceroid. It
      is likely that damaged basal keratinocytes provide debris for the formation of
      the latter. "Oral ceroid granuloma' would be an appropriate term for collections
      of such reactive macrophages occurring in the oral tissues.

PMID- 8887083
TI  - The relationship between the adenine nucleotide metabolism and the conversion of
      the xanthine oxidase enzyme system in ischemia-reperfusion of the rat small
      intestine.
AB  - The time course of the energy metabolism after reperfusion, the relationship
      between the conversion of xanthine dehydrogenase to xanthine oxidase (D-to-O
      conversion) during ischemia, and the changes of the energy metabolism after
      reperfusion were studied using an ischemia-reperfusion model in the small
      intestine of the rat. The rat jejunum underwent an occlusion of the superior
      mesenteric artery and vein for either 30 minutes (group 1, n = 6) or 90 minutes
      (group 2, n = 6) with collateral interruption, and then it was reperfused. The
      contents of the adenine nucleotides in the small intestine of the rat were
      measured by high-performance liquid chromatography (HPLC) before ischemia, and
      30, 60, and 90 minutes of ischemia, as well as 30, 60, 120, and 180 minutes after
      reperfusion. The recovery level of adenosine triphosphate (ATP) in group 1 (6.05
      +/- 0.80 mumol/g dry weight) 30 minutes after reperfusion was significantly
      higher than that in group 2 (2.28 +/- 1.12 mumol/g dry weight) (P < .001). In
      addition, the ATP content after reperfusion in group 2 did not change from 30 to
      180 minutes after reperfusion. The D-to-O conversion during ischemia in group 1
      was not significantly greater than that before ischemia; however, that of group 2
      did increase significantly during ischemia (P < .005). These results suggest that
      the tissue damage from ischemia-reperfusion injury after reperfusion under 90
      minutes' ischemia is accomplished within the first 30 minutes after reperfusion.
      Therefore, the ATP level at 30 minutes after reperfusion may be useful for the
      evaluation of intestinal viability. Thus, the conversion of the xanthine oxidase
      enzyme system might play an important role in the expression of ischemia
      reperfusion injury.

PMID- 8887084
TI  - The effect of allopurinol pretreatment on intestinal hypoperfusion encountered
      after correction of intestinal volvulus.
AB  - After reversal of blood flow following a prolonged period of ischemia, blood flow
      returns for a few seconds and is reduced afterward. This is called "no-reflow
      phenomenon." Antioxidants such as allopurinol have been shown to prevent the
      occurrence of this phenomenon in organs other than the intestine. An experimental
      study was conducted to investigate the effect of allopurinol pretreatment on
      intestinal blood flow after correction of intestinal volvulus in rabbits. In
      group 1, baseline intestinal blood flow (IBF) was evaluated using radiolabeled
      red blood cells. In group 2, 720 degrees intestinal volvulus was created and IBF
      was evaluated 6 hours later. In group 3, intestinal volvulus was created and
      devolvulus was performed 6 hours later. Intraperitoneal isotonic saline was
      injected 60 minutes before correction of the volvulus. IBF was evaluated after
      correction of the volvulus. Group 4 had the same procedures as group 3, but
      allopurinol (200 mg/kg) was injected in place of the isotonic saline. IBF stopped
      6 hours after volvulus. Compared with the baseline group, IBF was significantly
      lower in the group with volvulus + devolvulus (P < .01). The IBF of the
      allopurinol-treated group was significantly higher than that of the isotonic
      saline group (P < .01) and it did not differ significantly from that of the
      baseline group. Histopathological examination showed that intestinal volvulus
      leads to histological injury. The histological injury was more pronounced in the
      devolvulus group and was less severe in the allopurinol group in comparison to
      the isotonic saline pretreatment group (P < .01). It is concluded that
      allopurinol pretreatment prevents the intestinal hypoperfusion (no-reflow
      phenomenon) and histological injury encountered after correction of intestinal
      volvulus of 6 hours' duration.

PMID- 8887085
TI  - Congenital spigelian hernia with cryptorchidism.
AB  - Congenital spigelian hernia (SH) is a rarity. The authors present two cases of
      congenital SH with undescended testis, and examine the significance of the
      concurrence of these events.

PMID- 8887086
TI  - Long-term results after megaureter folding in children.
AB  - In 56 megaureters treated by the folding technique, good results were obtained in
      52 (93%). Complications in four ureters included stenosis (2) and vesico-ureteral
      reflux (2). The width of the megaureters and minor renal calyces, the degree of
      hydronephrosis, and the serum urea and creatinine levels decreased significantly
      after the operation. The renal parenchyma thickness and the creatinine clearance
      level increased significantly.

PMID- 8887087
TI  - Early versus delayed repair of reduced incarcerated inguinal hernias in the
      pediatric population.
AB  - This study concerns 183 pediatric patients (age range, 14 days to 10 years) who
      initially presented with incarcerated inguinal hernias. In all of them, initial
      conservative management to reduce the hernia was successful. This consisted of
      elevation of the lower half of body and sedation and/or gentle manual pressure.
      Thereafter, 75 of them had "early" operation (within 72 hours). Early surgery was
      not possible for the other 108 patients because of various reasons. These
      patients were discharged from the ward and were scheduled for "delayed" repair
      within 1 to 3 months. The complication rates were similar for the two groups, but
      17 (15.7%) of the 108 patients in the delayed group had repeat incarceration,
      some of them more than once during the waiting period. Reincarceration occurred
      as early as 5 days and as late as 120 days after the initial discharge. The
      authors conclude that the results of delayed repair were unfavorably affected by
      the recurrent incarceration, and therefore all pediatric patients should have
      hernia repair within 5 days after the reduction of incarceration.

PMID- 8887089
TI  - Penopubic flaps technique for the repair of epispadias with or without exstrophy:
      a preliminary report.
AB  - Six patients (average age, 2 1/2 years; range, 4 months to 8 years) with the
      exstrophy-epispadias complex and isolate epispadias were treated using an
      alternative method. An inverted U-shaped incision (with a length of approximately
      3 to 5 cm and a width of approximately 0.7 to 1.0 cm) was prepared, extending
      from the penopubic urethral meatus toward the umbilicus. The two incisions were
      extended along the urethral plate toward the ventral face of the glans. The pubic
      flap was prepared from the skin or scar tissue on the pubic area. The neourethra
      was reconstructed using penopubic flaps. A fistula occurred in one patient, which
      healed spontaneously. The penopubic flaps enabled us to form a wide-enough
      urethral tube and to perform a better dissection on the pubic area.

PMID- 8887088
TI  - The spectrum of ureteropelvic junction obstructions occurring in duplicated
      collecting systems.
AB  - The authors reviewed four cases of ureteropelvic junction obstruction (UPJ) in
      duplicated systems. Associated abnormalities included contralateral duplication,
      vesicoureteral reflux, and a case of ipsilateral upper pole ectopic ureter with a
      dysplastic upper pole moiety. Surgical management included dismembered
      pyeloplasty, ureteral reimplantation, end-to-side pyeloureterostomy to the upper
      pole ureter, and upper-pole heminephrectomy with lower-pole dismembered
      pyeloplasty. UPJ obstructions occurring in duplicated systems often are
      associated with other anomalies.

PMID- 8887090
TI  - Testicular neovascularization by "omentotesticulopexy': a possible adjuvant in
      the surgical correction of high undescended testes.
AB  - The surgical repair of "very high" undescended testes may bring about testicular
      atrophy, as a result of impaired vascular supply, whether caused unintentionally
      by extensive dissection, or deliberately when the Fowler-Stephens operation is
      employed. In this experimental study, improvement of the vascular supply by means
      of "omentotesticulopexy" (an omental flap pexied to the rat testis) before or
      concomitant with spermatic vessel division (known as the Fowler-Stephens
      operation) was achieved and demonstrated by angiographic studies. The authors
      believe that the addition of "omentotesticulopexy" to the Fowler-Stephens
      operation will reduce the rate of testicular atrophy among patients with high
      undescended testes.

PMID- 8887091
TI  - Gastric tube as the primary procedure for pure esophageal atresia.
AB  - Long gap esophageal atresia occurs in approximately 5% of patients with
      tracheoesophageal anomalies. A small group of such patients have a rudimentary or
      diverticular distal esophagus that is not amenable to primary repair. These
      children usually require staged procedures and esophageal replacement using other
      parts of the intestinal tract. To circumvent the morbidity and delayed repair
      associated with cervical esophagostomy, colon interposition, or delayed gastric
      tube interposition, the authors propose the use of a primary gastric tube for
      early establishment of esophageal continuity in the neonate. Three cases of early
      esophageal replacement using a gastric tube are described. All three patients
      were born prematurely, with comorbid conditions, and had a rudimentary distal
      esophagus. The results of the operation were successful. The authors believe that
      primary repair of the esophagus, when possible, is the gold standard.

PMID- 8887092
TI  - Anterior sagittal anorectoplasty for anorectal malformations and perineal trauma
      in the female child.
AB  - Vestibular fistula and perineal ectopic anus are the most common anorectal
      malformations in female children. Anterior saggital anorectoplasty (ASARP) was
      used to treat 416 patients with these anomalies, as well as cases of perineal
      canal and third-degree perineal tear, during a 20 year period. Preliminary
      colostomy was performed in only four patients, who had a perineal tear. For
      ASARP, a midline incision was made and the rectum was separated from the vagina
      and placed in the center of the sphincteric muscle complex. The perineal body was
      reconstructed, and normal appearance of the perineum was achieved. Six patients
      had complications postoperatively (4 had secondary hemorrhage, 2 had wound
      infection). One patient with hemorrhage and one with infection required laying
      open of the wound and revision surgery after 12 weeks. Both recovered well. Of
      the 416 patients, 397 returned for follow-up 12 weeks after the surgery. Of
      these, 390 had a normal-looking perineum and normal defecation. Of the remaining
      seven patients, three had retraction of the rectum, one had recurrence of the
      fistula, and another had acquired perineal canal. These five children required
      revision ASARP and recovered successfully. The other two patients had mucosal
      prolapse, which reduced spontaneously. Three hundred twenty-six children of the
      416 patients have had follow-up beyond the age of 3 years. Of these, 291 had
      normal bowel habits without the use of laxatives. Of the other 35, four had fecal
      impaction of unknown etiology, which was managed conservatively, 6 had anal
      stenosis (four underwent posterior Barrow's flap interposition and two responded
      to dilatation), and 25 had a posterior ledge that caused constipation and
      required cutback. Overall, eight patients (1.9%) required revision ASARP and 40
      others (9.8%) had minor complications. This operation provides consistently good
      results, and the authors recommend it for the management of anorectal
      malformations and perineal trauma in female children.

PMID- 8887093
TI  - Successful transplantation of human hepatoblastoma into immunodeficient mice.
AB  - Six hepatoblastomas (HBs) from pediatric patients were transplanted into
      immunodeficient NMRI nu/nu mice. Cells from two fetal HBs did not develop tumors.
      In contrast, xenografts derived from three nonpretreated HBs and one HB after
      three courses of chemotherapy, all comprising embryonal cells, showed growth
      after 8 to 10 weeks. The take rates of HB varied from 60% to 90% (mean, 80%).
      Histologically, they resembled their originals in the pattern of fetal and
      embryonal differentiated areas and contained hematopoietic foci. The tumors
      produced high levels of alpha-feto-protein in the patients and the animals. In
      contrast to the patients, tumor-bearing mice did not display elevated platelet
      counts. During serial grafting, growth rates of the tumors gradually increased,
      and hematopoiesis was no longer detectable; however, histologically, a
      dedifferentiation could not be clearly identified. The addition of viable human
      or murine fibroblasts to inoculated cells of three nude mouse HBs resulted in a
      significant increase in the growth rate of all tumors and reappearance of
      hematopoiesis in three of the examined 10 xenografts of one HB. The authors
      conclude that HB xenografts in immunodeficient mice are a feasible in vivo model
      for studies of the biological behavior of this tumor.

PMID- 8887094
TI  - Experimental ureterohydronephrosis in fetal rats.
AB  - This study tests the hypothesis that prenatal exposure to 2,4-dichlorophenyl-p
      nitrophenyl ether (nitrofen), an herbicide known to induce pulmonary hypoplasia
      and other malformations in fetal rats, also may induce ureterohydronephrosis
      (UHN) and oligohydramnios. Time-dated pregnant Wistar rats were given 100 mg of
      the chemical on day 9 or 11 of gestation, and the findings in their fetuses were
      compared with those of suitable controls. Marked bilateral UHN was found in the
      majority of exposed fetuses, but without evidence of either mechanical
      obstruction or dysplastic parenchymal lesions. These animals had various degrees
      of lung hypoplasia. The amount of fluid in their amniotic sacs was increased
      rather than decreased and it was independent of lung weight but correlated to
      some extent with UHN grade. Urinary tract dilatation and polyhydramnios in this
      model most likely are attributable to polyuria caused by nitrofen-induced
      impairment of renal concentrating capacity. This relatively simple animal model
      might facilitate research into some aspects of the physiology of nonobstructive,
      prenatally dilated urinary tracts.

PMID- 8887095
TI  - Renal impairment after surgical resection of neuroblastoma.
AB  - Postoperative renal impairment was observed in 6 of 58 patients with
      neuroblastoma treated between November 1982 and March 1994. To clarify the
      clinical characteristics of these patients (renal-impairment group), they were
      compared with 26 patients treated during the same period who did not have renal
      impairment (no-impairment group). The incidence of primary retroperitoneal tumor
      and invasion of the hilum renalis was clearly higher in the renal-impairment
      group than in the group with no impairment. However, no significant difference
      was observed with respect to age, tumor laterality, or stage of disease. The
      results of postoperative biochemical examinations showed that the serum
      concentrations of lactic dehydrogenase were significantly higher in the renal
      impairment group. In the group with renal impairment, the mean maximal body
      temperatures on the first, second, and third postoperative days were 38.7 degrees
      C, 38.6 degrees C, and 38.1 degrees C, respectively. These were higher than those
      of the no-impairment group. For patients with these risk factors, intraoperative
      prophylactic measures and early postoperative renal blood flow evaluation (in
      anticipation of postoperative renal impairment) are considered necessary.

PMID- 8887096
TI  - Influence of severe underlying pathology and hypovolemic shock on the development
      of acute pancreatitis in children.
AB  - Acute pancreatitis in children is a little known and poorly defined disease, and
      thus rarely considered in the diagnosis of pediatric abdominal pain. In the past
      14 years, the authors treated 21 children who had acute pancreatitis. Trauma was
      the cause of the disease in 29% of the patients. One third (33%) had hypovolemic
      shock-related pancreatitis (mostly after either cardiopulmonary bypass or severe
      gastrointestinal bleeding). Furthermore, a major proportion (38%) had severe
      underlying organic disease. The clinical presentation was unremarkable; most
      patients (83%) had abdominal pain, especially in the epigastrium, and vomiting
      was the only other clinical sign exhibited by more than 50%. The Glasgow score (a
      severity grading system based on eight laboratory values and calculated within
      the first 48 hours after admission) had good specificity but poor sensitivity.
      Amylasemia had no predictive value. More than half our patients (57%) had
      complications, mainly pseudocysts (24%) and relapse (14%), and about one quarter
      (24%) had severe pancreatitis. There were two deaths (10%), and all surviving
      children (90%) eventually were symptom-free. Treatment was conservative in the
      majority of cases; eight patients (38%) required surgery. Hypovolemic shock and a
      severe underlying pathology were identified as risk factors for the occurrence of
      severe pancreatitis (P < .005) or death (P < .001), but not for the development
      of complications.

PMID- 8887097
TI  - Endoscopic treatment of vesico-ureteric reflux in neurogenic bladder--8 years'
      experience.
AB  - During an 8-year period, 51 children with neurogenic bladder had endoscopic
      injection of Teflon (STING) for the management of 69 refluxing ureters. There
      were 21 boys and 30 girls (age range, 10 month to 16 years). Vesico-ureteral
      reflux (VUR) had been present for a mean of 4.1 years, and severity distribution
      was as follows: grade I, 1 ureter; grade II, 5 ureters, grade III, 9 ureters;
      grade IV, 39 ureters; and grade V, 15 ureters. The follow-up period ranged from 3
      months to 8 years (mean, 4 years). Reflux ceased in 57 ureters (82%); in four
      ureters the VUR recurred (9 months to 6 years later). Bilateral vesico-ureteric
      junction (VUJ) obstruction occurred in one patient, which required surgical
      correction 3 years after STING. These data suggest that for difficult cases of
      VUR in neurogenic bladders, STING is a safe and effective option and should be
      the initial treatment of choice. However, because of the possibility of late
      recurrence of VUR or obstruction at the VUJ, long-term follow-up is required.

PMID- 8887098
TI  - Clinical implications of phrenic nerve injury after pediatric cardiac surgery.
AB  - Phrenic nerve injury with resulting diaphragm paralysis occurred in 25 (1.5%) of
      1,656 cardiac surgical procedures in children during a 10-year period. Phrenic
      nerve injury was most commonly noted in patients who had undergone previous
      cardiac surgery (16 of 165, 10%; P < .0001), typically after a previous Blalock
      Taussig shunt (10 of 53, 19%; P = .007). Plication of the diaphragm (7 thoracic,
      4 abdominal) was performed in 11 patients (44%). Indications for plication were
      inability to wean from mechanical ventilation (5 patients) and persistent or
      recurrent respiratory distress (6 patients). The patients who needed diaphragm
      plication were significantly younger than those who were managed conservatively
      (median, 11 months [4 days to 23 months] versus 20 months [4 months to 16 years];
      P = .01). All patients older than 2 years were extubated within 3 days (mean, 1.5
      days) and did not need any surgical intervention. The median follow-up period was
      3.2 years, and no patient has had recurrent respiratory problems. There were no
      deaths as a direct result of phrenic nerve injury. Phrenic nerve injury after
      cardiac surgery is a serious complication that often leads to respiratory
      insufficiency in patients under than 2 years of age. For such patients, early
      diaphragm plication is a simple and effective procedure that prevents the
      complications of prolonged mechanical ventilation.

PMID- 8887099
TI  - Enteric fistulas and necrotizing enterocolitis.
AB  - The incidence, presentation, significance, and outcome of infants with internal
      enteric fistula formation secondary to necrotizing enterocolitis (NEC) were
      examined. Of 130 infants with NEC treated during a 7-year period, an enteric
      fistula developed in five (4%). The gestational age of these patients (3 boys, 2
      girls) ranged from 25 to 40 weeks and their birth weight ranged from 800 to 3,460
      g. Two had Down's syndrome. Plain abdominal radiographs showed widespread
      intramural gas in all, and portal vein gas in two. Four patients required early
      laparotomy, which confirmed extensive intestinal necrosis; a diverting
      jejunostomy or ileostomy was constructed in three, and the abdomen was closed
      with drainage in one. Fistulas were diagnosed by contrast radiology between 16
      and 51 days after the onset of NEC, and were jejunocolic (2), ileocolic (2), and
      colocolic (1). They were associated with enteric stricture(s), an inflammatory
      mass, and clinical signs of intermittent sepsis. One infant with an ileocolic
      fistula died of sepsis before definitive surgical treatment. Of the four who
      underwent surgery, two survived after limited intestinal resection, but one of
      the two with short bowel syndrome died. Enteric fistula formation is a rare
      complication of NEC. Typically it occurs with colonic stricture(s) and is
      associated with signs of incomplete bowel obstruction and intermittent sepsis.
      Resectional surgery is successful, but there appears to be a significant risk of
      short bowel syndrome.

PMID- 8887100
TI  - Transanal mucosectomy: a modification of the Soave procedure for Hirschsprung's
      disease.
AB  - In the Soave procedure for Hirschsprung's disease, the mucosectomy of the
      aganglionic segment of colon is performed transabdominally. The authors describe
      an innovative modification of the standard Soave procedure, in which a transanal
      mucosectomy is performed as the abdominal incision is made. The transanal
      mucosectomy technique was compared with the conventional approach. From 1974 to
      1993, 51 patients underwent a Soave procedure for Hirschsprung's disease. Twenty
      six (51%) had the standard Soave procedure (STD) (1974-1984), and 25 (49%) had
      the modified procedure (MOD) (1984-1994). In the latter, the entire mucosal
      dissection was performed through a transanal approach. Surgical data were
      accumulated by database analysis. Each case was entered into a database at the
      time of operation, and follow-up data were obtained through mail-in
      questionnaires or personal communication. The two groups were comparable with
      respect to number, gender distribution, and average age at the time of operation.
      There were two superficial wound infections in the STD group and two superficial
      wound infections and one death (secondary to cardiac arrest in a patient with
      trisomy 21 and a severe congenital cardiac anomaly) in the MOD group. The average
      postoperative stay for the STD group was 10.8 days; that for the MOD group was
      6.8 days (t test: P < .0001). The operating time was shorter for the MOD
      procedure. Follow-up data were available for 25 (96.2%) patients in the STD group
      and 25 (100%) in the MOD group. The two groups were comparable in all respects
      except for the average length of follow-up, which was longer for the STD group.
      No patients had, urinary incontinence or sexual dysfunction (when applicable).
      Overall, patients/parents in both groups rated the outcome as "good." This
      modification of the Soave technique for Hirschsprung's disease is both safe and
      effective. Compared with the standard procedure, it is associated with shorter
      operating time (because the transanal mucosectomy is performed as the abdomen is
      opened) and a shorter stay postoperatively. The results have been excellent.

PMID- 8887101
TI  - Pulmonary hemorrhage: a novel complication after extracorporeal life support.
AB  - Pulmonary hemorrhage (PH) occurs infrequently as a complication in neonates with
      respiratory failure. Major PH has been observed at the authors' institution in
      several neonates after "successful" completion of extracorporeal life support
      (ECLS) therapy. The authors sought to determine the incidence of PH and the risk
      factors associated with this unique and newly described morbidity after ECLS. The
      hospital records of all patients who had PH after ECLS were reviewed. The control
      patients were the first three infants who underwent ECLS just before each PH
      case. PH was defined as the occurrence of bloody tracheal secretions associated
      with a deterioration in pulmonary status. Demographics, ventilator/ECLS
      parameters, fluid management, coagulation, and laboratory studies were evaluated
      in the pre-ECLS, during ECLS, and in the post-ECLS period. From 1985 to 1993, 13
      (6%) of 214 neonates suffered major PH, at a mean time of 43.2 +/- 9.2 hours
      after the ECLS course. The overall mortality rate for children with PH was 38%,
      compared with 5% among the control patients. In the pre-ECLS phase, patients with
      PH required more fluid (153.6 +/- 20.2 mL/kg/d v 106.8 +/- 10.2 mL/kg/d) and were
      acidemic for a longer period (2.3 +/- 1.2 hours v 0.6 +/- 0.2 hours; pH < 7.25).
      No differences were noted in AaDo2 or oxygenation index criteria. During ECLS,
      inotropes were required more often (23% v 0%; P < .01) because hypotension was
      more common (77% v 33%; P < .05). Activated clotting times (ACT) and heparin
      requirements were equivalent for the two groups. After ECLS the patients with PH
      required longer ventilatory assistance (184.9 +/- 48.2 hours v 83.4 +/- 16.7
      hours) and supplemental oxygen (24.3 +/- 3.0 days v 17.2 +/- 1.9 days). No
      coagulation abnormalities were identified at the time of PH. Higher SGPT (185.4
      +/- 146.4 U/L v 22.6 +/- 3.5 U/L; P < .05) and BUN (69.3 +/- 7.5 mg/dL v 47.2 +/-
      5.9 mg/dL; P < .05) also were noted for the patients with PH. PH represents an
      important and novel morbidity in neonates after ECLS. Prolonged acidosis, a high
      fluid requirement before ECLS, the need for blood pressure support during ECLS,
      and evidence of renal and/or hepatic dysfunction serve to identify patients who
      have a high risk for the development of this complication.

PMID- 8887102
TI  - Focal nodular hyperplasia of the liver with the lumbo-costovertebral syndrome.
AB  - Congenital lumbar hernia is uncommon in children; only 42 cases have been
      reported. A newborn girl with congenital superior lumbar hernia associated with
      lumbo-costovertebral syndrome is described. Associated features include focal
      nodular hyperplasia of the liver, absent right kidney and hydrocephalus.

PMID- 8887103
TI  - Extracorporeal membrane oxygenation in pediatric respiratory failure secondary to
      smoke inhalation injury.
AB  - Extracorporeal membrane oxygenation (ECMO) was used successfully in two children
      who had respiratory failure secondary to smoke inhalation injury. The first
      involved a 20% body surface area burn with initial carboxyhemoglobin of 26%. The
      patient developed varicella pneumonia, which complicated his respiratory failure;
      he was placed on ECMO for 7 days. The second infant had a 35% body surface area
      burn and carboxyhemoglobin of 30%. He underwent debridement and allografting
      while on ECMO, and was decannulated after 13 days. Anticoagulation for ECMO did
      not significantly interfere with dressing changes. Both patients had definitive
      autografting and were discharged home breathing room air.

PMID- 8887104
TI  - Gastroschisis complicated by midgut atresia and closure of the defect in utero.

PMID- 8887105
TI  - Gastric outlet obstruction caused by prepyloric web in a case of Down's syndrome.
AB  - The authors describe an infant with Down's syndrome who had a prepyloric web
      complicated by severe gastric outlet obstruction. The delay in diagnosis was
      responsible for malnutrition and the early postoperative complications of
      hypothermia and hypoglycemia. Awareness of the association of gastrointestinal
      abnormalities with Down's syndrome will enable appropriate evaluation for early
      diagnosis of this surgically correctable malformation.

PMID- 8887106
TI  - Gallbladder malformation with gastric wall-like architecture.
AB  - A 3-year-old girl was found to have a distended gallbladder, which pathologically
      consisted almost entirely of a gastric-type wall, featuring muscularis mucosae
      and a well-developed bilayered muscularis propria. This appears to be a unique,
      not previously recognized, malformation of the gallbladder.

PMID- 8887107
TI  - A rare case of an antenatally diagnosed tumor of the neck--a hamartoma of the
      thyroid gland.
AB  - A case of connatal hamartoma of the left thyroid lobe is reported. During routine
      prenatal ultrasonographic examination, a tumor of the neck was diagnosed. The
      baby was born at 30 weeks' gestation, and the tumor (measuring 7.0 x 5.5 x 4.2
      cm) was extirpated. Histologically, the tumor was a hamartoma of the thyroid
      gland. Follow-up evaluation (3 and 6 months after resection) showed that the
      child was doing well and had no signs of hypothyroidism or hypoparathyroidism.
      The case is discussed with respect to antenatal diagnosis, postpartum diagnostic
      measures, management, and surgical therapy.